PMID- 26862932 TI - Ratio of platelet count/spleen diameter predicted the presence of esophageal varices in patients with schistosomiasis liver cirrhosis. AB - AIM: To examine the platelet count (PC)/spleen diameter (SD) ratio in predicting the presence of esophageal varices (EV) in patients with schistosomiasis liver cirrhosis. MATERIALS AND METHODS: A total of 95 consecutive patients with EV induced by schistosomiasis liver cirrhosis were enrolled in this trial. A total of 141 schistosomiasis liver cirrhosis patients without EV were enrolled as controls. All patients were diagnosed by endoscopy. Demographic, laboratory, and Doppler ultrasound parameters were collected and analyzed. Binary logistic regression analysis was carried out to identify independent risk factors associated with EV occurrence. Receiver operating curves were generated to obtain the PC/SD ratio cutoff values for the optimal sensitivity and specificity with respect to EV. RESULTS: The accuracy was increased in diagnosing for EV using the ratio of PC/SD compared with the SD alone [area under the curve: 0.891 95% confidence interval (CI): 0.844-0.928 vs. 0.764 95% CI: 0.705-0.817; P<0.01]. The optimal cutoff value was 1004, with a 77.1% (95% CI: 67.9-84.8%) positive predictive value and an 89.3% (95% CI: 82.7-94.0%) negative-predictive value. Using a cutoff of 1004, it was determined that 117/141 (83.0%) patients without EV could avoid undergoing unnecessary endoscopy, whereas 14/95 (14.7%) patients with EV would be misdiagnosed. In contrast, when the ratio was set at 909, the positive-predictive and negative-predictive values were 79.5% (95% CI: 69.5 87.4%) and 83.1% (95% CI: 76.1-88.8%), respectively. A ratio of 909 would accurately predict the absence of EV in 123/141 (87.2%) patients; however, 24/95 (25.3%) patients with EV would miss the necessary screening endoscopy. CONCLUSION: The ratio of PC/SD was a useful marker in predicting the presence of EV in patients with schistosomiasis liver cirrhosis. PMID- 26862933 TI - Pulmonary functions in children with inflammatory bowel disease. AB - OBJECTIVE: To investigate fractional exhaled nitric-oxide (FeNO) levels in children with Crohn's disease (CD) and ulcerative colitis (UC) and their correlation to disease activity. MATERIALS AND METHODS: Children with CD and UC (aged 8-18 years) and age-matched healthy controls without respiratory symptoms were recruited. Disease activity was assessed using validated scores. All children performed spirometry and FeNO tests and the association between intestinal disease parameters and pulmonary functions was studied. RESULTS: Thirty-five children with CD, nine with UC, and 24 healthy controls were enrolled. The mean FeNO level was higher in children with CD compared with the controls. Increased FeNO levels (>23 parts per billion) were more common among CD and UC compared with healthy children (46, 33, and 0%, respectively, P<0.05). Nevertheless, FeNO levels did not correlate with disease activity. There were no significant differences between CD, UC patients, and healthy controls in any of the spirometric variables. CONCLUSION: FeNO level, a marker of airway inflammation, is elevated in children with inflammatory bowel diseases irrespective of their intestinal disease activity. Increased FeNO levels are not associated with respiratory symptoms, suggesting a latent pulmonary involvement in the systemic disease. PMID- 26862934 TI - Factors associated with impaired quality of life in French patients with chronic idiopathic constipation: a cross-sectional study. AB - OBJECTIVE: Chronic idiopathic constipation can impact the health-related quality of life (QoL). We aimed to evaluate QoL in French patients with different clinical types of chronic constipation. METHODS: In this cross-sectional study, 338 general practitioners included 1710 consecutive adult patients who fulfilled the Rome III criteria for constipation and agreed to complete Patient-Assessment of Constipation Quality of Life and Symptom questionnaires. Sociodemographic and medical data were collected. Multivariate analyses enabled identification of factors associated with poor QoL using odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Overall, 1673 patients were eligible for analyses; 32% had infrequent evacuation (IE) of feces, 24% had difficult evacuation (DE) of feces, and 44% had both (IE+DE). The mean global Patient-Assessment of Constipation Quality of Life score was 1.9 (95% CI: 1.9-2.0), with a significantly worse QoL for IE+DE patients (mean 2.0; 95% CI: 2.0-2.1); 23% of patients reported a poor QoL, that is, a more than 2.4 (29% in IE+DE group, P<0.0001). Poor QoL was significantly associated with psychosocial parameters, associated digestive symptoms, but the main factors were the use of rectal treatment (OR 2.5; 95% CI: 1.9-3.3), one or less defecation/week (OR 3.5; 95% CI: 2.2-5.7), and weak/null perceived treatment efficiency (OR 4.3; 95% CI: 2.8-6.5). CONCLUSION: Chronic constipation is associated with a significant decrease in QoL, especially in patients suffering from both infrequent and DE of feces and feeling unsatisfied by their treatments. PMID- 26862935 TI - Brain potentials associated with the shape Stroop effect. AB - Event-related potentials (ERPs) were recorded to explore, for the first time, the electrophysiological correlates of the shape Stroop effect. Fifteen healthy individuals were presented with a frame and a name of an object with a typical shape in life and asked to categorize the object's typical shape in life as a 'circle', a 'square,' or a 'triangle' by pressing the relevant button as quickly as possible. Accurate categorization of the name of an object was faster when it was presented with a congruent shape frame (e.g. name of a tyre/circle frame) than with an incongruent one (e.g. name of a tyre/square frame). Scalp ERPs analysis showed that the incongruent condition elicited a more negative component N430 and a more late positive component LPC than the congruent condition. N430 is a critical sign of conflict detection in the early stage, whereas late positive component reflects the response conflict in the late stage. The results provided evidence for the dissociation between conflict detection and conflict resolution in the shape Stroop effect. PMID- 26862936 TI - Using Digital Image Correlation to Characterize Local Strains on Vascular Tissue Specimens. AB - Characterization of the mechanical behavior of biological and engineered soft tissues is a central component of fundamental biomedical research and product development. Stress-strain relationships are typically obtained from mechanical testing data to enable comparative assessment among samples and in some cases identification of constitutive mechanical properties. However, errors may be introduced through the use of average strain measures, as significant heterogeneity in the strain field may result from geometrical non-uniformity of the sample and stress concentrations induced by mounting/gripping of soft tissues within the test system. When strain field heterogeneity is significant, accurate assessment of the sample mechanical response requires measurement of local strains. This study demonstrates a novel biomechanical testing protocol for calculating local surface strains using a mechanical testing device coupled with a high resolution camera and a digital image correlation technique. A series of sample surface images are acquired and then analyzed to quantify the local surface strain of a vascular tissue specimen subjected to ramped uniaxial loading. This approach can improve accuracy in experimental vascular biomechanics and has potential for broader use among other native soft tissues, engineered soft tissues, and soft hydrogel/polymeric materials. In the video, we demonstrate how to set up the system components and perform a complete experiment on native vascular tissue. PMID- 26862937 TI - Apical Resection Mouse Model to Study Early Mammalian Heart Regeneration. AB - Cardiovascular disease plagues the whole world due to intensive lifestyle changes. Heart regeneration holds great promise for repairing and restoring cardiomyocytes lost due to injury and disease. In contrast to the robust cardiac regeneration of certain lower vertebrates, adult mammalian hearts typically show minimal capacity for heart regeneration and repair. However, recent studies have sparked considerable scientific interest with the finding that, between postnatal day 1 to 7 (P1 to P7), the neonatal mouse heart retains significant regenerative potential after apical resection (i.e., surgical amputation and exposure of left ventricular apex). One major controversy over this finding might be due to the diverse surgery-related procedures used in efforts to replicate or expand upon this important finding. These instructions dynamically present the materials and methodology for apical resection in a mouse model. The salient steps of this rodent survival surgery involve hypothermia anesthesia, thoracotomy, surgical amputation of heart ventricular apex, and suture and recovery of mice. The approach described could expand the application of the apical resection mouse model for cardiovascular research. PMID- 26862938 TI - Increased Ghrelin Levels and Unchanged Adipocytokine Levels in Major Depressive Disorder. AB - OBJECTIVE: One of the hypotheses of the pathophysiology of major depressive disorder (MDD) proposes that there is a relationship between adipocytokine and ghrelin levels and depression. METHODS: Patients with major depression with a BMI <=25 kg/m2 between the ages of 11 and 18 years (n = 30) were compared with a healthy control group (n = 30). Both groups were evaluated across a pretreatment period (MD-PT) and an improved period (MD-I). We measured serum leptin, adiponectin, resistin, and ghrelin levels and other parameters related to metabolic syndrome, such as glucose, insulin, insulin resistance (homeostasis model assessment [HOMA]), triglycerides (TG), and total cholesterol (TCHOL). RESULTS: Leptin, adiponectin, and resistin levels did not differ across groups; however, ghrelin levels were increased in the MD-I group compared with the control and MD-PT groups (p < 0.05). HOMA levels were also higher in the MD-PT group than in the control group (p < 0.05). After treatment, there was no difference in this measurement. CONCLUSIONS: The relationship between adipocytokines and major depression may be dependent on ghrelin levels as a result of antidepressant treatment and subsequent obesity. PMID- 26862940 TI - 500-mA ECT-A Proof of Concept Report. PMID- 26862939 TI - Identification of Critical Conditions for Immunostaining in the Pea Aphid Embryos: Increasing Tissue Permeability and Decreasing Background Staining. AB - The pea aphid Acyrthosiphon pisum, with a sequenced genome and abundant phenotypic plasticity, has become an emerging model for genomic and developmental studies. Like other aphids, A. pisum propagate rapidly via parthenogenetic viviparous reproduction, where the embryos develop within egg chambers in an assembly-line fashion in the ovariole. Previously we have established a robust platform of whole-mount in situ hybridization allowing detection of mRNA expression in the aphid embryos. For analyzing the expression of protein, though, established protocols for immunostaining the ovarioles of asexual viviparous aphids did not produce satisfactory results. Here we report conditions optimized for increasing tissue permeability and decreasing background staining, both of which were problems when applying established approaches. Optimizations include: (1) incubation of proteinase K (1 ug/ml, 10 min), which was found essential for antibody penetration in mid- and late-stage aphid embryos; (2) replacement of normal goat serum/bovine serum albumin with a blocking reagent supplied by a Digoxigenin (DIG)-based buffer set and (3) application of methanol rather hydrogen peroxide (H2O2) for bleaching endogenous peroxidase; which significantly reduced the background staining in the aphid tissues. These critical conditions optimized for immunostaining will allow effective detection of gene products in the embryos of A. pisum and other aphids. PMID- 26862941 TI - Solid-State Li-Ion Batteries Using Fast, Stable, Glassy Nanocomposite Electrolytes for Good Safety and Long Cycle-Life. AB - The development of safe, stable, and long-life Li-ion batteries is being intensively pursued to enable the electrification of transportation and intelligent grid applications. Here, we report a new solid-state Li-ion battery technology, using a solid nanocomposite electrolyte composed of porous silica matrices with in situ immobilizing Li(+)-conducting ionic liquid, anode material of MCMB, and cathode material of LiCoO2, LiNi1/3Co1/3Mn1/3O2, or LiFePO4. An injection printing method is used for the electrode/electrolyte preparation. Solid nanocomposite electrolytes exhibit superior performance to the conventional organic electrolytes with regard to safety and cycle-life. They also have a transparent glassy structure with high ionic conductivity and good mechanical strength. Solid-state full cells tested with the various cathodes exhibited high specific capacities, long cycling stability, and excellent high temperature performance. This solid-state battery technology will provide new avenues for the rational engineering of advanced Li-ion batteries and other electrochemical devices. PMID- 26862942 TI - Supernumerary nipples--a new finding in Williams syndrome. PMID- 26862943 TI - Temple syndrome misdiagnosed as Silver-Russell syndrome. PMID- 26862944 TI - 25-Gauge Vitrectomy with Epiretinal Membrane and Internal Limiting Membrane Peeling in Eyes with Very Good Visual Acuity. AB - PURPOSE: To evaluate the efficacy and safety of pars plana vitrectomy (PPV) in patients with epiretinal membrane (ERM) and preoperative visual acuity (VA) of 20/40 or better. METHODS: 44 eyes that underwent PPV and ERM peeling were included in this retrospective study. Data retrieved included demographic information, VA and intraocular pressure (IOP) preoperatively, after 1 month, 6 months and at final visit, presence of metamorphopsia, surgical reports, and occurrence of any complications. RESULTS: Mean preoperative VA was 20/36 (0.24 +/ 0.08 logMAR) and had improved to 20/27 (0.13 +/- 0.11 logMAR) at the final follow-up (p < 0.001). Thirty (68.1%) eyes had improved by 1 line of vision or more, and 10 (22.7%) achieved final 20/20 vision. Significant improvement in vision was achieved earlier in eyes that underwent vitrectomy combined with cataract extraction. Preoperative OCT scans demonstrated preserved outer retinal layer structure. CONCLUSIONS: PPV and ERM peeling is a safe and effective procedure in eyes with very good preoperative VA. PPV combined with cataract extraction offers a faster improvement in VA than PPV alone with deferred cataract surgery. PPV should be considered in symptomatic eyes with ERM and VA of 20/40 or better, in order to preserve and even improve the VA. PMID- 26862945 TI - Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy. AB - The goal of the study was to examine expression of prostate-specific membrane antigen (PSMA) in neovasculature of gynecologic cancers, as PSMA-targeted therapy has showed a promise in treatment of advanced carcinomas. The study included cervical carcinoma (n=28), vulvar carcinoma (n=20), endometrial carcinoma (n=23), primary ovarian carcinoma (n=21), metastatic ovarian carcinoma (n=25), and normal cervix (n=12) as negative control. All cases were immunostained using anti-CD31 antibody to delineate capillary endothelial cells. In parallel, all cases were immunostained using anti-PSMA antibody. The PSMA staining was assessed in tumor capillaries and in normal tissues and scored as a percentage of CD31 staining. PSMA expression was found in the tumor neovasculature, and no significant expression was identified in vasculature of normal tissues. The extent of PSMA staining in tumor capillaries varied from high expression in ovarian and endometrial cancers, to medium expression in cervical squamous cell carcinomas, and low expression in cervical adenocarcinomas and vulvar cancers. All (100%) cases of primary ovarian carcinoma, ovarian carcinoma metastases, and primary endometrial carcinoma showed PSMA expression in tumor vasculature, which was diffuse in majority of cases. The expression of PSMA in ovarian cancer metastases was similar among different metastatic foci of the same tumor. Fifteen percent of cervical squamous cell carcinoma, 50% of cervical adenocarcinoma, and 75% of vulvar carcinomas showed no capillary expression of PSMA. In conclusion, PSMA is highly and specifically expressed in the neovasculature of ovarian, endometrial, and cervical squamous carcinoma, rendering it a potential therapeutic vascular target. PMID- 26862946 TI - Ki67 Labeling Correlated With Invasion But Not With Recurrence. AB - Pituitary adenomas account for 10% to 15% of intracranial neoplasms. Multiple factors had been introduced for tumor recurrence. MIB-1 monoclonal antibody, a marker of the proliferative index, has been introduced in various tumors, but unfortunately, the usefulness of MIB-1 in predicting the behavior of pituitary adenoma has been debated recently. Hence, the aim of this study was to evaluate its role in the recurrence and the invasiveness of pituitary adenomas. In a cross sectional study conducted between 2005 and 2010, patients with a diagnosis of pituitary adenoma, referred to 2 medical centers (Arad and Iran Mehr hospital) in Tehran, were enrolled. Clinical and laboratory data were gathered. Immunostaining for MIB-1 monoclonal antibody was performed for each slide and scored blindly by 2 pathologists. A total of 176 surgically treated patients met the inclusion criteria. Thirty-six of 176 cases had recurrent episodes. Eleven of 176 patients had invasive tumors. The mean Ki67 index was 2.7%+/-3.96% in recurrent cases and 2.24%+/-2.35% in nonrecurring cases, with no statistically significant difference between them (P>0.05). Ten of 11 invasive pituitary tumors had a Ki67>3%, and a statistically significant difference was observed between invasive and noninvasive tumors (P<0.05). Hence, the Ki67 index seems to be suitable for predicting invasion, but it failed to show any correlation between Ki67 and tumor recurrence. PMID- 26862947 TI - The Potential Diagnostic Utility of TROP-2 in Thyroid Neoplasms. AB - OBJECTIVES: Human trophoblast cell-surface marker (TROP-2) has been reported to be overexpressed in various human carcinomas (CAs) and suggested to be a prognostic marker for some CAs. The diagnostic utility of TROP-2 in CAs has not been explored. METHODS: Immunohistochemical evaluation of TROP-2 expression on tissue microarray sections of 136 thyroid neoplasms, surgical specimens of 61 atypical thyroid follicular-patterned lesions [including 33 papillary thyroid carcinomas (PTCs), 17 atypical follicular neoplasms (AFNs), and 11 adenomatoid nodules with focal nuclear atypia (ANFNA)], and 20 benign thyroid lesions, as well as 10 cytology specimens of PTCs was performed. For comparison, immunoassay for Hector Battifora mesothelial-1 (HBME-1), galectin-3, and cytokeratin 19 was performed on the 61 atypical thyroid follicular-patterned lesions. RESULTS: Strong membranous staining with TROP-2 was seen in 94% (33/35) of classic PTCs and 81% (30/37) of confirmed follicular variant PTCs on tissue microarray and routine surgical sections, as well as 100% (10/10) of PTCs on cytology specimens; it was not observed in follicular adenomas (n=51) or CAs (n=37), AFNs or ANFNA (n=28), benign (n=20) or normal (n=15) thyroid tissue. In contrast, the expression of HBME-1 and galectin-3 was identified in 100% (33/33) of surgical cases of PTCs and in 57% (16/28) and 50% (14/28) of AFNs and ANFNA, respectively. CONCLUSIONS: Our findings demonstrate that a membranous TROP-2 staining pattern is highly specific for PTC, which may serve as a potential diagnostic marker aiding in the accurate classification of morphologically equivocal thyroid follicular-patterned lesions. PMID- 26862948 TI - Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma. AB - Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target. PMID- 26862949 TI - Characterizing Molecular Variants and Clinical Utilization of Next-generation Sequencing in Advanced Breast Cancer. AB - Women with advanced breast carcinomas have few therapeutic options. Recent advances in genomic profiling represent a new paradigm of cancer classification and treatment, but experience with genomic testing in a clinical setting remains limited. We retrospectively determined the genomic variants and correlate these with histology [histomorphologic subtype, nuclear grade, standard immunohistochemistry (IHC)] and clinical utilization (ordering, turnaround time, report review, and targeted therapy). Among 48 patients, 2 showed no genetic alterations, 11 (23%) showed variants of unclear significance only and 35 (73%) showed variant(s) affecting function (VaF) and/or variants of unclear significance. Overall, 119 variants were observed in 20 of 50 tested genes. Each patient had a unique molecular profile, with numerous (n=58) variants not previously reported in breast cancer. VaF detected in more than 2 patients included: TP53 (n=21), PIK3CA (n=20), and FGFR1 (n=3). VaF comprised 46 single nucleotide variants (79%), 7 amplifications (12%), 3 frameshifts (5%), 1 insertion (2%), and 1 deletion (2%). The tested samples had very high Ki67 index (average 57%+/-23%) and approximately half were hormone receptor and HER2 negative (25/46, 54%). Metastatic breast carcinomas showed a higher average VaF versus breast-localized tumors (1.3+/-0.99 vs. 0.18+/-0.60, P<0.05). Next generation sequencing reports were promptly reported and reviewed (average 1 to 2 d) and 7 (~25%) of potentially eligible patients received targeted therapy. Advanced breast cancers show unique landscapes of genetic variants. Most testing was done in late disease, often in metastatic and receptor-negative carcinomas. Next-generation sequencing results were promptly reported and reviewed, but the utilization of targeted therapies was limited. PMID- 26862950 TI - Downexpression of Matriptase-2 Correlates With Tumor Progression and Clinical Prognosis in Oral Squamous-Cell Carcinoma. AB - The aim of this study was to investigate the relationship of matriptase-2 expression with the clinicopathologic characteristics, the histologic grade, and patient survival in oral squamous-cell carcinoma (OSCC). Immunohistochemical analysis of matriptase-2 expression was performed in 102 surgical specimens from patients with OSCC. The immunohistochemical results were further verified by quantitative real-time reverse transcription-polymerase chain reaction. The immunostaining intensity was scored on a scale ranging from 0 (absence of staining) to 3 (intense staining). The distribution score was determined by the percentage of stained cells on a scale ranging from 0 (<5%), 1 (5% to 25%), 2 (25% to 50%), 3 (50% to 75%), to 4 (75% to 100%). The immunoscore of matriptase-2 expression was the product of the above 2 scores and ranged from 0 to 12 for analysis. Faint matriptase-2 immunostaining was observed in the non-neoplastic oral mucosal epithelia. The matriptase-2 immunoscore was significantly higher in well-differentiated OSCCs than in poorly differentiated tumors (P=0.001). Moreover, a reduced matriptase-2 immunoscore was inversely correlated with the tumor size (P=0.017), a positive nodal stage (P=0.008), distant metastasis (P=0.032), and a late clinical stage (P=0.001). A lower immunoscore of matriptase 2 expression revealed a significant association with poor survival (P=0.003). Our results demonstrate that the inverse expression of matriptase-2 correlates with tumor progression and an advanced TNM stage, and has a poor prognosis in patients with OSCC. These findings suggest that the expression of matriptase-2 may be both a prognostic marker and a potential therapeutic target for this cancer. PMID- 26862951 TI - Expression Pattern of the BCL6 and ITM2B Proteins in Normal Human Brains and in Alzheimer Disease. AB - We reported that the integral membrane 2B gene (ITM2B, also called BRI2) is a target of BCL6 repression in lymphomas. Molecular alterations in ITM2B are associated with 2 neurodegenerative diseases, Familial British and Danish dementia, and dysregulation of ITM2B function has been implicated in the pathogenesis of Alzheimer disease (AD). Although ITM2B expression has been studied, the distribution of BCL6 in human brain has not been described. Our goal is to analyze BCL6 and ITM2B localization in normal human brains and in AD by immunohistochemistry to understand their relationship. We found that, in general, they have a reciprocal relationship. BCL6 expression is present in isolated cortical neurons, granule cells in the cerebellum, scattered glial cells, and in some cells of the ependyma and choroid plexus. ITM2B is expressed in most cortical neurons, neurons of the hippocampus and dentate nucleus, cerebellar Purkinje and granule cells, and (newly described here) in focal neurons in the basal ganglia, many neurons of the thalamus and brainstem, many cells in the ependyma and choroid plexus, and in the smooth muscle of blood vessels. ITM2B expression is prominent in plaques in AD-containing dystrophic neurites but absent in neurofibrillary tangles; BCL6 expression is absent in neurofibrillary tangles and in the nuclei of cells associated with plaques in AD. It is essential to understand the localization of BCL6 and ITM2B in the brain before considering manipulation of their expression as a potential therapeutic tool. PMID- 26862952 TI - NRASQ61R Mutation-specific Immunohistochemistry is Highly Specific for Either NRASQ61R or KRASQ61R Mutation in Colorectal Carcinoma. AB - Anti-epidermal growth factor receptor-targeted therapy is only indicated in RAS wild-type colorectal carcinomas (CRCs). It is recommended that both NRAS and KRAS mutation testing to be performed before a CRC is considered RAS wild-type. Given that mutation-specific immunohistochemistry (IHC) has been shown to be sensitive and specific for the detection of NRAS mutations in melanoma, we assessed the specificity of NRAS mutation-specific IHC in CRC. IHC was performed on tissue microarrays containing 2823 consecutive CRC undergoing surgery with curative intent using a novel mutation-specific antibody to the protein produced by the NRAS mutation (clone SP174). Tissue microarrays were assessed by 2 observers and all IHC-positive or equivocal cases were repeated on whole sections to confirm the result. Positive cases then underwent molecular testing by matrix-assisted laser desorption/ionization-time of flight polymerase chain reaction. In total, 22 of 2823 (0.8%) CRCs demonstrated confirmed positive staining with complete interobserver concordance. RAS mutations were confirmed in all IHC-positive CRCs. In total, 11 cases harbored the NRASQ61R mutation. Surprisingly, 11 cases demonstrated the KRASQ61R mutation. We conclude that mutation-specific IHC with this currently available NRASQ61R antibody is highly specific for the presence of either NRASQ61R or KRASQ61R mutations in CRC. We caution that we did not assess the sensitivity of IHC and that this antibody does not detect other RAS mutations. Therefore, negative staining does not exclude a clinically significant RAS mutation. However, positive staining confirms the presence of an NRASQ61R or KRASQ61R mutation without the need for further molecular testing. PMID- 26862953 TI - Intratumoral FOXP3+ Regulatory T Cells in Diffuse Large B-Cell Lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in Egypt and worldwide. Gene expression profiling classifies DLBCL into: germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) DLBCL. Hans' algorithm has high concordance with gene expression profiling results. Regulatory T cells (Tregs) represent important modulators for the interaction between lymphoma cells and host microenvironment. FOXP3 is a popular single marker for Tregs. There is little information about the possible role of Tregs in high-grade lymphoma such as DLBCL. This study aims to assess the prognostic impact of FOXP3+ Tregs in DLBCL. The study was carried out on 70 archival cases (61 de novo DLBCL and 9 reactive follicular hyperplasia cases). DLBCL cases were classified into GCB and non-GCB groups using Hans' algorithm. All studied cases are subjected to FOXP3 immunostaining. Density of FOXP3+ Tregs was higher in reactive cases compared with DLBCL (P=0.000). In DLBCL cases, FOXP3 expression was associated with free spleen (P=0.02), early stage (P=0.05), centroblastic variant (P=0.003), and absence of necrosis (P=0.05). In germinal cases, density of FOXP3 was significantly higher in cases with good PS (P=0.02), very good and good revised international prognostic index (P=0.002), and low-risk age-adjusted international prognostic index >60 (P=0.01). Non germinal DLBCL cases with negative FOXP3 were significantly associated with splenic involvement (P=0.005). DLBCL cases with high FOXP3 have longer survival (P=0.03). T cells in the background of DLBCL may play a role in modulation of tumor progression. Their presence is associated with favorable prognostic parameters in DLBCL. PMID- 26862954 TI - Detecting early stage osteoarthritis by optical coherence tomography? AB - Osteoarthritis (OA) is the most common chronic disease of our joints, manifested by a dynamically increasing degeneration of hyaline articular cartilage (AC). While currently no therapy can reverse this process, the few available treatment options are hampered by the inability of early diagnosis. Loss of cartilage surface, or extracellular matrix (ECM), integrity is considered the earliest sign of OA. Despite the increasing number of imaging modalities surprisingly few imaging biomarkers exist. In this narrative review, recent developments in optical coherence tomography are critically evaluated for their potential to assess different aspects of AC quality as biomarkers of OA. Special attention is paid to imaging surface irregularities, ECM organization and the evaluation of posttraumatic injuries by light-based modalities. PMID- 26862955 TI - Caspase-3 Activity in the Rat Amygdala Measured by Spectrofluorometry After Myocardial Infarction. AB - Myocardial infarction (MI) has dramatic mid- and long-term consequences at the physiological and behavioral levels, but the mechanisms involved are still unclear. Our laboratory has developed a rat model of post-MI syndrome that displays impaired cardiac functions, neuronal loss in the limbic system, cognitive deficits and behavioral signs of depression. At the neuronal level, caspase-3 activation mediates post-MI apoptosis in different limbic regions, such as the amygdala - peaking at 3 days post-MI. Cognitive and behavioral impairments appear 2-3 weeks post-MI and these correlate statistically with measures of caspase-3 activity. The protocol described here is used to induce MI, collect amygdala tissue and measure caspase-3 activity using spectrofluorometry. To induce MI, the descending coronary artery is occluded for 40 min. The protocol for evaluation of caspase-3 activation starts 3 days after MI: the rats are sacrificed and the amygdala isolated rapidly from the brain. Samples are quickly frozen in liquid nitrogen and kept at -80 degrees C until actual analysis. The technique performed to assess caspase-3 activation is based on cleavage of a substrate (DEVD-AMC) by caspase-3, which releases a fluorogenic compound that can be measured by spectrofluorometry. The methodology is quantitative and reproducible but the equipment required is expensive and the procedure for quantifying the samples is time-consuming. This technique can be applied to other tissues, such as the heart and kidneys. DEVD-AMC can be replaced by other substrates to measure the activity of other caspases. PMID- 26862956 TI - Functional Rhinoplasty. PMID- 26862957 TI - Evaluation of the Patient with Nasal Obstruction. AB - Nasal obstruction is often multifactorial and knowledge of the contributing factors is critical to appropriate evaluation, diagnosis, and execution of a treatment plan. Recognizing and appropriately managing all components of nasal obstruction will increase the likelihood of symptomatic improvement and patient satisfaction. PMID- 26862958 TI - Does the Nose Have a Function Beyond Breathing? AB - This article examines how functional nasal surgery can result in aesthetic improvement to the nose. We performed a literature search examining functional rhinoplasty with resultant aesthetic benefits. We also conducted a review of various techniques that can be used to correct functional nasal obstruction that also achieve aesthetic improvement(s).Although there are data demonstrating improvements to quality of life after functional and aesthetic nasal surgery, there is limited work linking the close relationship between functional nasal surgery with resultant aesthetic improvements.Functional rhinoplasty to correct nasal obstruction can also result in aesthetic improvements. Perhaps reconsideration of separating these closely tied issues is needed. A formal study looking at the degree of worsened, unchanged, and improved nasal aesthetics that occurs after true functional rhinoplasty, from both objective and subjective viewpoints, should be considered. PMID- 26862959 TI - The Nasal Airway: A Critical Review. AB - Functional nasal surgery is frequently performed and deeply embedded in otolaryngology. However, unequivocal proof of its efficacy is still pending, leading some health authorities toward restrictive policies. In this article, we review the evidence and suggest that reexamining the paradigm of functional nasal surgery may be appropriate. PMID- 26862960 TI - Extracorporeal Septoplasty: External and Endonasal Techniques. AB - Severe septal deformities are among the most challenging problems faced by rhinoplasty surgeons. Extracorporeal septoplasty (ES)--also known as subtotal septal reconstruction--involves removal of the native deformed septum and replacement with a reconstructed neoseptum. Several techniques and multiple variations have been described in the literature. We present an overview of ES, pertinent anatomical structures and deformities, and the external versus endonasal approach, and describe some of our techniques. PMID- 26862961 TI - Spreader Grafts in Functional Rhinoplasty. AB - Management of the middle vault is paramount to achieving optimal aesthetic and functional outcomes in rhinoplasty. The ideal treatment for middle vault complications, such as internal nasal valve collapse, inverted-V deformity, and middle vault dorsal asymmetry, is prevention. Risk factors for middle vault problems in rhinoplasty that may be identified in preoperative consultation include short nasal bones, long and weak upper lateral cartilages, thin skin, previous trauma or surgery, preoperative positive Cottle maneuver, tension nose deformity, and anteriorly positioned inferior turbinates. When any of these risk factors are identified, preventive measures should be pursued. These include preservation of middle vault support structures, judicious resection in dorsal hump reduction, use of conservative osteotomies, and reconstruction of the cartilaginous middle vault with structural grafting. Spreader grafts have become the workhorse in middle vault reconstruction. They are invaluable in restoring nasal dorsal aesthetic lines, repairing or maintaining the internal nasal valve, and buttressing a corrected crooked nose. Functional and aesthetic problems related to the middle nasal vault are among the most common reasons for patients seeking revision rhinoplasty. Although complications in rhinoplasty are inevitable, underlying their etiology and instituting prophylactic treatment can significantly help reduce their occurrence. PMID- 26862962 TI - The Autospreader Flap for Midvault Reconstruction following Dorsal Hump Resection. AB - Dorsal hump reduction without adequate reconstitution of the midvault can often result in cosmetic or functional problems. One of the simplest techniques to avoid these problems is the use of the excess upper lateral cartilage to reconstruct the midvault (the spreader flap or autospreader). Herein we outline the history of the technique and present the specific indications and contraindications, as well as describe our method for achieving it successfully. Case studies are presented with the specific indications. Grafting alternatives to the spreader flap are also outlined. The spreader flap technique offers multiple advantages, including maximal use of local tissues, simplicity, and airway preservation. Disadvantages are the use of an external approach and the inability to use it alone in the presence of severe asymmetries. PMID- 26862963 TI - The Conchal Cartilage Butterfly Graft. AB - Nasal obstruction due to weakening of the nasal sidewall is a very common patient complaint. The conchal cartilage butterfly graft is a proven technique for the correction of nasal valve collapse. It allows for excellent functional results, and with experience and attention to technical detail, it may also provide excellent cosmetic results. While this procedure is most useful for restoring form and function in cases of secondary rhinoplasty following the reduction of nasal support structures, we have found it to be a very powerful and satisfying technique in primary rhinoplasty as well. This article aims to describe the butterfly graft, discuss its history, and detail the technical considerations which we have found useful. PMID- 26862964 TI - Form and Function of the Nasal Tip: Reorienting and Reshaping the Lateral Crus. AB - Dysfunction of the external nasal valve affects both the form and function of the nose. Successful treatment of these problems is dependent on proper analysis and diagnosis of the aberrant anatomy. Cephalic malpositioning of the lateral crura has been described for nearly 30 years. Repositioning of the lateral crura in a more caudal orientation with lateral crural strut grafts will correct aesthetic abnormalities and reinforce the external nasal valve. Sagittal malpositioning has been more recently described and also has deleterious effects on both the shape of the nasal tip and breathing. Reorienting the short axis of the lateral crus is another powerful tool for the rhinoplasty surgeon to correct the weak and narrow external nasal valve. PMID- 26862965 TI - Rhinoplasty of the Aging Nose. AB - The process of aging leads to countless bodily changes on both a macro- and microscopic scale. No organ system is unaffected; however, the nose is especially susceptible. Sun damage, hormone levels, regenerative capability, tissue elasticity, bone resorption, and the effects of gravity contribute to produce classic signs and symptoms. Rhinoplasty of the aging nose requires a comprehensive understanding of aging facial anatomy combined with surgical techniques designed to resist these ubiquitous remodeling forces over time. PMID- 26862966 TI - Mitek Suspension of the Lateral Nasal Wall. AB - The nasal valve has long been described as the anatomical boundary most likely to inhibit nasal airflow and lead to subsequent nasal obstruction. Although many procedures can address this area to improve the nasal airway, for over 20 years, suture lateralization of the external nasal valve has been described as a minimally invasive technique that can improve nasal breathing. We report our modification of the standard technique in which we lateralize the placement of the bone-anchored suture and incorporate Gore-Tex within the nasal vestibular incision to prevent tissue migration. PMID- 26862967 TI - Causes and Prevention of Secondary Obstruction. AB - Secondary nasal obstruction occurs when surgery fails to improve a patient's nasal obstruction symptoms. This may occur from failure to recognize a problem preoperatively or failure to address mucocutaneous medical ailments. Secondary obstruction may even occur despite perfect execution of the operative plan. In this article, we discuss the etiology, intraoperative pitfalls, and surgical correction of secondary obstruction after primary rhinoplasty. When managing postrhinoplasty secondary obstruction, care must be taken to correct the cause of obstruction without creating new problems. PMID- 26862968 TI - Evolution of Preoperative Rhinoplasty Consult by Computer Imaging. AB - The preoperative consultation in rhinoplasty involves a multitude of actions that are mandatory for the decision-making process: history taking with attention to the symptoms and specific requests of the patient, clinical evaluation of the aesthetics, the functional status of the nose and the patients' motivation for surgery, and acquisition of standardized preoperative photographs. During the last decade, computer imaging or morphing of the preoperative pictures of the nose has become much more common. This part of the consultation allows the surgeon and patient to reach a mutually agreeable set of expectations by demonstrating the planned outcome of rhinoplasty and describing the objectives of surgery. The evolving literature on computer imaging supports that the benefits for both the patients and surgeons seem to outweigh the risks. Indeed, morphing enables the surgeon to precisely explain to the patients the goal of surgery, and to postpone or even cancel surgery in the group of patients that do not appear satisfied with the proposed changes. In addition, patients may feel more prepared for surgery and have a more realistic view of the outcome of the intervention. Presently, computer imaging is progressing from 2D to 3D models, optimizing the surgeons' capacity to perform morphing in the most advantageous manner for both parties. The current review provides a state-of-the art analysis on morphing in rhinoplasty, putting morphing into a historic and relevant perspective in clinical practice. PMID- 26862969 TI - Three-Dimensional Surface Imaging and the Continuous Evolution of Preoperative and Postoperative Assessment in Rhinoplasty. AB - During the preoperative assessment in rhinoplasty, the surgeon takes a thorough history, performs a complete examination by assessing functional and aesthetic aspects of the nose, obtains a clear understanding of the patient's wishes, conducts facial analysis based on standardized photography, and communicates to the patient the goals and pitfalls of surgery. Computer imaging or morphing of the preoperative pictures of the nose has drawn a lot of interest in the last decade, and it is a sign of evolution of the preoperative consultation. Technological advances, also in the context of rhinoplasty, have led to the development of three-dimensional (3D) imaging techniques, and have completely revolutionized the way that surgeons manage their patients preoperatively and evaluate postoperative results today. The accurate 3D surface imaging aids the surgeon to communicate with the patient adequately before surgery, to set an appropriate surgical plan, and to measure the shape and volume changes of the patient's nose that result from the intervention. The present review provides an analysis on the current knowledge of 3D surface imaging in rhinoplasty derived from the literature, and highlights future directions of preoperative and postoperative assessment in the field. PMID- 26862970 TI - An Economical Approach to Ethnic Asian Rhinoplasty. AB - Septal cartilage is deficient in Asians seeking augmentation rhinoplasty. Economized utilization of resources is necessary for durable tip enhancement that complements a dorsal implant. We introduce a modified tongue-in-groove method designed to transmit forces across the dorsum, eliminating the need for robust caudal support and prioritizing nasal lengthening and tip projection. We aim to promote the roundness index parameter and demonstrate the feasibility of a novel method in the context of Asian rhinoplasty. Between 2012 and 2014, a total of 104 Taiwanese patients underwent rhinoplasty with dorsal augmentation and lengthening with a modified tongue-in-groove technique. The concept borrows from methods established by Byrd, Guyuron, and Toriumi but distinguished by exaggerated forward positioning of a septal extension graft. Paired extended spreader grafts obviate the need for a columellar strut. Soft-tissue changes were analyzed with photogrammetry. A new parameter, the roundness index, was measured. Tip projection, dorsal length, nasal height, alar and columellar length increased significantly after 5.5 months of follow-up. Nasal tip angle, roundness, columella-labial angle, and nostril axis inclination decreased. There were no statistically significant differences in the magnitude of change in patients followed for less than and greater than 6 months. The most common complication was new or persistent tip deviation in five cases (5%). This technique was designed for a nasal anatomy typified by deficient septal cartilage. Significant photogrammetric changes were maintained after 6 months. Economized tissue allocation, dorsal septal load sharing, and relative independence from caudal support are key features of this feasible method. PMID- 26862971 TI - A Retrospective 3D Radiologic Analysis of 52 Patients with Mandible Fractures. AB - When fractured, mandible angulates. For better preoperative evaluation, movements of fractured mandibular segments should be documented in x-, y-, and z-axes. This article quantitatively evaluates the pattern and degree of the angulation. Fifty two patients with mandible fractures were involved in this study. After defining a three-dimensional (3D) coordination system consisting of the x-axis (the axis directed from the medial to lateral side of the skull), y-axis (directed from the inferior to superior side), and z-axis (directed from the posterior to anterior side), the degree with which the fractured mandible angulated around each of these axes was measured using 3D graphic software. The tendency of the angulation was compared between the three axes. Frequency of complications, operation times, maxilla mandibular fixation (MMF) need, and epidemiologic data were compared with the angulation results. Angulation around the x-axis was the most frequent with a 55.8% incidence, followed by a substantial margin of angulation around the y-axis with a 21.2% incidence; angulation around the z-axis was rare, with an incidence of 15.4%. Furthermore, the degree of z-axis angulation was minor compared with x- and y-axes angulations. There were statistically increased rate of complications, operation time, and MMF need in patients with more than 10 degrees of angulation in any case. Operation time and complication rates are also increased in patients with internal rotation of the proximal segment. Preoperative evaluation of mandible fracture angulation degree is useful for determining postoperative complication rates, MMF need, and operative challenge. This finding is helpful for effective performance to reposition the fractured mandible. PMID- 26862972 TI - Spare Roof Technique: A Middle Third New Technique. AB - To our knowledge, the spare roof technique (SRT) is the first technique that is based on a complete skeletonization/preservation of the upper lateral cartilages. This technique is used to keep the natural roof of the nose's middle third, while dehumping and/or correcting the crooked septum. From January 2014 till March 2015, a total of 40 rhinoplasties were performed through the SRT: 28 reduction rhinoplasties, 6 complex crooked noses (with extracorporeal septoplasty), and 6 mixed cases. The SRT is an excellent middle third technique. The natural roof was kept and fitted the accurate new position in almost all cases with no surgical complexity. It is an easy technique with many applications and it is also very useful in the classical humpectomy of the Caucasian nose and correction of the crooked nose. PMID- 26862973 TI - Migrated Implant Causing Refractory Headache in Rhinoplasty. AB - Alloplastic materials are popular and readily available for use in nasal augmentations. Among them, silicone implant is one of the most widely used, especially in certain areas in Asia for its reasonable cost and relatively simple operative technique. A major disadvantage of silicone is its notorious mobility after implantation and rate of extrusion if traumatized or exposed. Here, an unusual complication of a silicone implant for rhinoplasty was presented. We report a case of a 58-year-old woman who had augmentation rhinoplasty 20 years ago suffered from headache for over a year. Brain lesion and neurologic causes were ruled out by neurologists and physician in family medicine. Local finding showed upwardly deviated nasion and vague shape of silicone implant underneath the skin on nasal dorsum. PMID- 26862976 TI - Steric hindrance inhibits excited-state relaxation and lowers the extent of intramolecular charge transfer in two-photon absorbing dyes. AB - The two-photon absorbing dye AF240 [1, (7-benzothiazol-2-yl-9,9-diethylfluoren-2 yl)diphenylamine] is modified by adding bulky alkyl groups to the diphenylamino moiety. Three new compounds are synthesized which have ethyl groups in both ortho positions of each phenyl ring (2), t-butyl groups in one ortho position of each phenyl ring (3), and t-butyl groups in the para position of each phenyl ring (4). The dyes are examined in several aprotic solvents with varying polarity to observe the effects of the sterically hindering bulky groups on the ground and excited-state photophysical properties. While the ground state shows minimal solvent dependence, there is significant dependence on the fluorescence quantum yield and lifetime, as well as the excited-state energy levels. This effect is caused by the formation of an intramolecular charge-transfer (ICT) state, which is observed in the solvents more polar than n-hexane and supported by TD-DFT calculations. Electronic effects of ortho or para alkyl substitution should be similar, yet drastic differences are observed. A red shift in the fluorescence maximum is observed in 4 relative to 1, yet a blue shift occurs in 2 and 3 because the substituents at the sterically sensitive ortho-positions inhibit excited-state geometric relaxation and result in less ICT character than 1. Coupled with theoretical calculations, the data support a planar ICT (PICT) excited state where the diphenylamino nitrogen in an sp(2)-like geometry is integral with the plane containing the fluorene and benzothiazole moieties. Ultrafast transient absorption experiments show that ICT occurs rapidly (<150 fs) followed by geometric and solvent relaxation in ~ 1-4 ps to form the PICT or solvent-stabilized ICT (SSICT) state. This relaxation is not observed in non polar n-hexane because the solvent dependent ICT state energy lies higher than the locally-excited (LE) state. Finally, formation of a triplet state (T1) is only efficiently observed in n-hexane for all four dyes. PMID- 26862978 TI - Multi-target Chromogenic Whole-mount In Situ Hybridization for Comparing Gene Expression Domains in Drosophila Embryos. AB - To analyze gene regulatory networks active during embryonic development and organogenesis it is essential to precisely define how the different genes are expressed in spatial relation to each other in situ. Multi-target chromogenic whole-mount in situ hybridization (MC-WISH) greatly facilitates the instant comparison of gene expression patterns, as it allows distinctive visualization of different mRNA species in contrasting colors in the same sample specimen. This provides the possibility to relate gene expression domains topographically to each other with high accuracy and to define unique and overlapping expression sites. In the presented protocol, we describe a MC-WISH procedure for comparing mRNA expression patterns of different genes in Drosophila embryos. Up to three RNA probes, each specific for another gene and labeled by a different hapten, are simultaneously hybridized to the embryo samples and subsequently detected by alkaline phosphatase-based colorimetric immunohistochemistry. The described procedure is detailed here for Drosophila, but works equally well with zebrafish embryos. PMID- 26862979 TI - In vitro analysis of partially hydrolyzed guar gum fermentation differences between six individuals. AB - Partially hydrolyzed guar gum (PHGG) is a fermentable, soluble, non-gelling fiber consumed as both a supplement and ingredient. PHGG supports bifidogenic and lactogenic growth, and increases the concentration of short chain fatty acids (SCFAs) in the distal intestine due to its fermentability. Changes in SCFA development due to the fermentation of dietary fibers in the colon have been widely studied, but there are limited studies analyzing the differences in SCFA development across multiple individuals (ages 23-68) exposed to the same dietary fiber (PHGG). With the six donors analyzed in this study, gas production varied from 59-80 mL/0.5 g fiber at 12 h and 85-93 mL/0.5 g fiber at 24 h between the six donors. At 12 h butyrate concentrations varied from 6.99 MUmol mL(-1) to 23.84 MUmol mL(-1) and from 8.78 MUmol mL(-1) to 22.84 MUmol mL(-1) at 24 h. Total SCFA concentration at 24 h ranged from 42.85 MUmol mL(-1) to 91.17 MUmol mL(-1). The overall average SCFA ratio for the six fecal donors was 30 : 45 : 25 (acetate : propionate : butyrate), which is similar to other fermentable fibers analyzed using in vitro systems. SCFA development in the distal intestine increases the amount of metabolizable energy from the diet, but varies greatly among people based primarily on the composition and changes of their gut microflora. With over a 2-fold difference in SCFA production, significant differences were found among healthy individuals fecal microflora when exposed to PHGG. Donor 6 SCFA concentrations decreased at 24 h, indicating a quicker fermentation process than the other five donors. All SCFAs measured fluctuated greatly among the six individuals within 24 h of analysis. Results of in vitro fermentation analyses are limited by the wide variation found with fecal donor. PMID- 26862980 TI - Tweaking Subtype Selectivity and Agonist Efficacy at (S)-2-Amino-3-(3-hydroxy-5 methyl-isoxazol-4-yl)propionic acid (AMPA) Receptors in a Small Series of BnTetAMPA Analogues. AB - A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4 yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at the four homomeric AMPA receptors expressed in Xenopus laevis oocytes. The analogues 6 and 7 exhibit very different pharmacological profiles with binding affinity preference for the subtypes GluA1 and GluA3, respectively. X-ray crystal structures of three ligands (6, 7, and 8) in complex with the agonist binding domain (ABD) of GluA2 show that they induce full domain closure despite their low agonist efficacies. Trp767 in GluA2 ABD could be an important determinant for partial agonism of this compound series at AMPA receptors, since agonist efficacy also correlated with the location of the Trp767 side chain. PMID- 26862984 TI - Key Elements for Judging the Quality of a Risk Assessment. AB - BACKGROUND: Many reports have been published that contain recommendations for improving the quality, transparency, and usefulness of decision making for risk assessments prepared by agencies of the U.S. federal government. A substantial measure of consensus has emerged regarding the characteristics that high-quality assessments should possess. OBJECTIVE: The goal was to summarize the key characteristics of a high-quality assessment as identified in the consensus building process and to integrate them into a guide for use by decision makers, risk assessors, peer reviewers and other interested stakeholders to determine if an assessment meets the criteria for high quality. DISCUSSION: Most of the features cited in the guide are applicable to any type of assessment, whether it encompasses one, two, or all four phases of the risk-assessment paradigm; whether it is qualitative or quantitative; and whether it is screening level or highly sophisticated and complex. Other features are tailored to specific elements of an assessment. Just as agencies at all levels of government are responsible for determining the effectiveness of their programs, so too should they determine the effectiveness of their assessments used in support of their regulatory decisions. Furthermore, if a nongovernmental entity wishes to have its assessments considered in the governmental regulatory decision-making process, then these assessments should be judged in the same rigorous manner and be held to similar standards. CONCLUSIONS: The key characteristics of a high-quality assessment can be summarized and integrated into a guide for judging whether an assessment possesses the desired features of high quality, transparency, and usefulness. CITATION: Fenner-Crisp PA, Dellarco VL. 2016. Key elements for judging the quality of a risk assessment. Environ Health Perspect 124:1127-1135; http://dx.doi.org/10.1289/ehp.1510483. PMID- 26862986 TI - Observing the Angular Distribution of Raman Scattered Fields. AB - In conventional optical spectroscopy, lenses are used to focus light on the sample and to collect light scattered from the sample. Focusing increases the signal intensity, but it amounts to angular (k-space) averaging and leads to information loss. In this issue of ACS Nano, Budde and collaborators record radiation patterns of Raman scattering from a single layer of graphene, revealing the angular distribution of the scattered field. The authors show that the radiation patterns render the spatial symmetry of vibrational modes. Furthermore, their results demonstrate that depolarization effects occurring in the focal region must be taken into account for proper interpretation of Raman intensities. We outline here the working principle of this new approach and discuss future applications for studies of graphene and other low-dimensional systems. PMID- 26862985 TI - EPA Method 1615. Measurement of Enterovirus and Norovirus Occurrence in Water by Culture and RT-qPCR. Part III. Virus Detection by RT-qPCR. AB - EPA Method 1615 measures enteroviruses and noroviruses present in environmental and drinking waters. This method was developed with the goal of having a standardized method for use in multiple analytical laboratories during monitoring period 3 of the Unregulated Contaminant Monitoring Rule. Herein we present the protocol for extraction of viral ribonucleic acid (RNA) from water sample concentrates and for quantitatively measuring enterovirus and norovirus concentrations using reverse transcription-quantitative PCR (RT-qPCR). Virus concentrations for the molecular assay are calculated in terms of genomic copies of viral RNA per liter based upon a standard curve. The method uses a number of quality controls to increase data quality and to reduce interlaboratory and intralaboratory variation. The method has been evaluated by examining virus recovery from ground and reagent grade waters seeded with poliovirus type 3 and murine norovirus as a surrogate for human noroviruses. Mean poliovirus recoveries were 20% in groundwaters and 44% in reagent grade water. Mean murine norovirus recoveries with the RT-qPCR assay were 30% in groundwaters and 4% in reagent grade water. PMID- 26862987 TI - Controlling the Polarity of Fullerene Derivatives to Optimize Nanomorphology in Blend Films. AB - Developing a design strategy to establish the compatibility of acceptor materials with donor materials is important for the rational development of organic solar cells. We synthesized 2,6-dimethoxyphenyl methanofullerene derivatives to realize an enhanced open-circuit voltage, and we investigated polarities and their effects on the film morphology of the active layer. The polarities of the synthesized fullerene derivatives were affected significantly by the presence of functional groups, such as methoxy, ether, and ester groups. Macro/nanoscopic morphological investigation and spectroscopic analysis of the blend films of the poly(3-hexylthiophene)(P3HT)/fullerene derivatives showed that a balanced polarity between materials results in the formation of optimized nanomorphology without grains and robust phase separation. Measurements of the device performance of the photovoltaic cells composed of P3HT and the fullerene derivatives confirmed the same tendency as that shown in the morphological analysis. This finding enables us to obtain an improved power conversion efficiency because of the enhanced open circuit voltage derived from the fullerene derivatives. PMID- 26862988 TI - Intranasal administration of oxytocin increases human aggressive behavior. AB - Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naive to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. PMID- 26862989 TI - Prevailing Photocurrent Generation of D-pi-A Type Oligo(phenyleneethynylene) in Contact with Gold over Dexter-Type Energy-Transfer Quenching. AB - Photocurrent generation is observed with D-pi-A type oligo(phenyleneethynylene) (OPE) physically contacting gold substrate. The OPE is conjugated with helical peptides, which helps the OPE moiety orient vertically on gold surface. This configuration makes the Dexter energy transfer difficult to occur even though one end of the D-pi-A type OPE physically contacts gold. The anodic photocurrent continuously increases with increment of applying bias voltage from -0.3 to 0.5 V. The first principle calculations reveal that the increase in photocurrent generation is attributed partly to the change in the electron distributions of HOMO and LUMO of the D-pi-A type OPE to be more localized with applying the positive potential. PMID- 26862990 TI - N-Iodosuccinimide-Promoted Cascade Trifunctionalization of Alkynoates: Access to 1,1-Diiodoalkenes. AB - An efficient cascade trifunctioalization reaction of alkynoates with N iodosuccinimide has been developed which proceeds through iodination, aryl migration, decarboxylation, and second iodination. This reaction represents an example of 1,1-difunctionalization of the acetylene bond and also provides a new strategy for the preparation of 1,1-diiodoalkenes. PMID- 26862991 TI - Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway. AB - Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 MUg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms. PMID- 26862992 TI - Evaluating a Tap Water Contamination Incident Attributed to Oil Contamination by Nontargeted Screening Strategies. AB - The present study applied nontargeted screening techniques as a novel approach to evaluate the tap water samples collected during the "4.11" tap water pollution incident occurred on April 11, 2014 in Lanzhou in west China. Multivariate analysis (PCA and OPLS-DA) of about 3000 chemical features obtained in extracts of tap water samples by ultrahigh-pressure liquid chromatography quadrupole time of-flight mass spectrometry (UPLC-QTOF-MS) analysis showed significantly different chemical profiles in tap water from pollution regions versus reference regions during the event. These different chemical profiles in samples from different regions were not observed in samples collected during the nonpollution period. The compounds responsible for the differences in profiles between regions were identified as naphthenic acids (NAs) and oxidized NAs (oxy-NAs) after the sample extracts underwent bromination to explore saturations, dansylation to identify hydroxylations and corresponding MS/MS mode analysis. A consistent finding was further observed in the targeted analysis of NA mixtures, demonstrating that the Lanzhou "4.11" tap water pollution incident could be attributed to oil spill pollution, and NA mixtures would be a marker for oil contamination. Such evaluations can help to rapidly discriminate pollution sources in accidental pollution events and contribute to regular water monitoring management of water safety issues. PMID- 26862993 TI - A Validated Tool Would Greatly Enhance Future Research on the Impact of Surgery on Sexual Function. PMID- 26862994 TI - Development of a Quantitative PCR Assay for Detection of Human Insulin-Like Growth Factor Receptor and Insulin Receptor Isoforms. AB - The biological activity of insulin and the insulin-like growth factor (IGF) ligands, IGF-I and IGF-II, is based in part on the relative abundance and distribution of their target receptors: the insulin receptor (IR) splice variants A (IR-A) and B (IR-B) and IGF 1 receptor (IGF-1R). However, the relative quantity of all three receptors in human tissues has never been measured together on the same scale. Due to the high homology between insulin receptor (IR)-A and IR-B proteins and lack of antibodies that discern the two IR splice variants, their mRNA sequence is the most reliable means of distinguishing between the receptors. Hence, highly specific primers for IR-A, IR-B, and IGF-1R mRNA were designed to accurately detect all three receptors by quantitative RT-PCR and enable direct quantification of relative receptor expression levels. A standard concentration curve of cDNA from each receptor was performed. Assay specificity was tested using competition assays and postamplification analysis by gel electrophoresis and cloning. Forward and reverse primer concentrations were optimized to ensure equal efficiencies across primer pairs. This assay enables a specific molecular signature of IGF/insulin signaling receptors to be assayed in different tissues, cell types, or cancers. PMID- 26862995 TI - No Evidence That RFamide-Related Peptide 3 Directly Modulates LH Secretion in the Ewe. AB - The neuropeptide RFamide-related peptide 3 (RFRP-3) has been implicated in the control of gonadotropin secretion in both birds and mammals. However, in mammals, depending on species, sex and photoperiod, inhibitory, excitatory, or no effect of RFRP-3 on the plasma concentration of LH has been reported. In the ewe, treatment with RFRP-3 either reduced LH concentration or had no effect, and treatment with an RFRP-3 receptor antagonist (ie, RF9) resulted in increased concentration of plasma LH. To clarify these conflicting results in the present study, a set of experiments was performed in ewes. Multiple iv injections of RFRP 3 (6 * 50 MUg) in ovariectomized ewes had no effect on plasma LH pulsatility. In intact ewes a bolus injection (500 MUg) or an injection (250, 500, or 1000 MUg) followed by a 4-hour perfusion (250, 500, or 1000 MUg . h(-1)) of RFRP-3 had no effect on the LH pulse induced by kisspeptin (6.5 MUg). In ovariectomized, estrogen-replaced ewes, the LH surge induced by estradiol benzoate was not modified by a 24-hour perfusion of RFRP-3 (500 MUg h(-1)). Finally, although treatment with RF9 induced a robust release of LH, treatment with a more selective RFRP-3 receptor antagonist, GJ14, resulted in no evident increase of LH. In contrast to the inhibitory effect previously suggested, our data are more consistent with the concept that RFRP-3 has no direct effect on LH secretion in ewes and that RF9 effect on LH release is likely not RFRP-3 receptor mediated. Hence, RFRP-3 probably has a minor role on the control of LH secretion in the ewe. PMID- 26862996 TI - ERalpha in Tac2 Neurons Regulates Puberty Onset in Female Mice. AB - A variety of data suggest that estrogen action on kisspeptin (Kiss1)-containing arcuate nucleus neurons (which coexpress Kiss1, neurokinin B (the product of Tac2) and dynorphin (KNDy) neurons restrains reproductive onset and function, but roles for estrogen action in these Kiss1 neurons relative to a distinct population of rostral hypothalamic Kiss1 neurons (which does not express Tac2 or dynorphin) have not been directly tested. To test the role for estrogen receptor (ER)alpha in KNDy cells, we thus generated Tac2(Cre) and Kiss1(Cre) knock-in mice and bred them onto the Esr1(flox) background to ablate ERalpha specifically in Tac2-expressing cells (ERalpha(Tac2)KO mice) or all Kiss1 cells (ERalpha(Kiss1)KO mice), respectively. Most ERalpha-expressing Tac2 neurons represent KNDy cells. Arcuate nucleus Kiss1 expression was elevated in ERalpha(Tac2)KO and ERalpha(Kiss1)KO females independent of gonadal hormones, whereas rostral hypothalamic Kiss1 expression was normal in ERalpha(Tac2)KO but decreased in ERalpha(Kiss1)KO females; this suggests that ERalpha in rostral Kiss1 cells is crucial for control of Kiss1 expression in these cells. Both ERalpha(Kiss1)KO and ERalpha(Tac2)KO females displayed early vaginal opening, early and persistent vaginal cornification, increased gonadotropins, uterine hypertrophy, and other evidence of estrogen excess. Thus, deletion of ERalpha in Tac2 neurons suffices to drive precocious gonadal hyperstimulation, demonstrating that ERalpha in Tac2 neurons typically restrains pubertal onset and hypothalamic reproductive drive. PMID- 26862998 TI - Reactions of gem-Difluorinated Phosphonium Salts Induced by Light. AB - gem-Difluorinated phosphonium salts, which are readily obtained from aldehydes and difluoromethylene phosphobetaine, can serve as a source of radicals under reductive conditions. An iridium complex or Hantzsch ester was used as a one electron reducing agent when irradiated with visible light. The fluorinated radicals were trapped with various alkenes, leading to products either via a photoredox cycle (for the iridium catalyst) or via a hydrogen atom transfer (for the Hantzsch ester). PMID- 26862997 TI - A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling. AB - Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of beta-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where beta-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-gamma, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects beta-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF. PMID- 26862999 TI - Changing the Ambulatory Training Paradigm. Design and Implementation of an Outpatient Pulmonology Fellowship Curriculum. AB - RATIONALE: The Accreditation Council for Graduate Medical Education has mandated that pulmonary fellows practice evidence-based medicine "across multiple care settings." Currently, most clinical fellowship training is inpatient based, suggesting that more robust fellowship training in outpatient pulmonology is needed. No standardized ambulatory pulmonary curriculum is currently available. OBJECTIVES: To design, implement and test the feasibility of a standardized, case based outpatient curriculum implemented for pulmonary fellows at the Perelman School of Medicine at the University of Pennsylvania. METHODS: A list of 20 topics in ambulatory pulmonology was generated and was used to create a series of literature-based teaching scripts, which served as the foundation for twice monthly small group teaching sessions. Before implementation, the fellows were asked to complete a survey regarding their impressions of their existing outpatient training and their competency in ambulatory patient care. Participants were surveyed again at 6 and 12 months thereafter. MEASUREMENTS AND MAIN RESULTS: Fellow survey respondents reported that the curriculum improved the overall ambulatory educational experience. Before implementation, only 6 of 12 fellows (50%) agreed that their current instruction on relevant outpatient pulmonary topics was adequate, compared with 100% after the curriculum (P = 0.01, n = 10). In addition, only five fellows (42%) initially agreed or strongly agreed that their current outpatient educational experience had prepared them well for independent pulmonary practice, compared with 90% on the 12-month survey (P = 0.02). CONCLUSIONS: We created a standardized outpatient pulmonary curriculum and demonstrated its feasibility in positively influencing fellows' perceived competency in ambulatory pulmonology. Additional assessment of knowledge, performance outcomes, and applicability at other institutions is needed. PMID- 26863000 TI - How molecular motors extract order from chaos (a key issues review). AB - Molecular motors are the workhorses of living cells. Seemingly by 'magic', these molecules are able to complete purposeful tasks while being immersed in a sea of thermal chaos. Here, we review the current understanding of how these machines work, present simple models based on thermal ratchets, discuss implications for statistical physics, and provide an overview of ongoing research in this important and fascinating field of study. PMID- 26863001 TI - Rapid Bead-Based Antimicrobial Susceptibility Testing by Optical Diffusometry. AB - This study combined optical diffusometry and bead-based immunoassays to develop a novel technique for quantifying the growth of specific microorganisms and achieving rapid AST. Diffusivity rises when live bacteria attach to particles, resulting in additional energy from motile microorganisms. However, when UV sterilized (dead) bacteria attach to particles, diffusivity declines. The experimental data are consistent with the theoretical model predicted according to the equivalent volume diameter. Using this diffusometric platform, the susceptibility of Pseudomonas aeruginosa to the antibiotic gentamicin was tested. The result suggests that the proliferation of bacteria is effectively controlled by gentamicin. This study demonstrated a sensitive (one bacterium on single particles) and time-saving (within 2 h) platform with a small sample volume (~0.5 MUL) and a low initial bacteria count (50 CFU per droplet ~ 105 CFU/mL) for quantifying the growth of microorganisms depending on Brownian motion. The technique can be applied further to other bacterial strains and increase the success of treatments against infectious diseases in the near future. PMID- 26863002 TI - C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean? AB - OBJECTIVES: Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis. METHODS: A total of 2777 patients admitted to the ICU of two centers between 2006-2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients' demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded. RESULTS: 1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2-4.6), 1.7 (1.2-2.4), 1.6 (1.2-2.1), 2.3 (1.4-3.8), 1.5 (1.1-2.1) times by the APACHE II>=13, SOFA score>=4, CRP>=4.0, LymC<0.45 and PLTC<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4-38.7) times by the combination of CRP>=4.0, lymC<0.45 and PLTC<150 (P<0.001). CONCLUSIONS: While WBCC, NeuC, Neu%, NLCR and EoC are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, LymC and PLTC can be used to determine the likelihood of sepsis. PMID- 26863003 TI - Dating of young groundwater using four anthropogenic trace gases (SF6, SF5CF3, CFC-12 and Halon-1301): methodology and first results. AB - A dedicated, GC-based analytical system is presented which allows detection of four anthropogenic trace gases (SF6, SF5CF3, CFC-12 and Halon-1301) in a single water sample, with detection limits and measurement uncertainties sufficiently low to employ them as quantitative indicators of groundwater age. The gases dissolved in water are extracted in the field using the method based on a dynamic head-space concept. In the laboratory, the investigated gases are cryogenically enriched, separated and measured using an electron capture detector. Reproducibility of the analyses is in the order of 2-5 %. The investigated tracers were measured in several production wells located in the recharge area of an intensively exploited aquifer in southern Poland. While the piston-flow ages of groundwater in the investigated wells revealed internal consistency, they appeared to be generally smaller than the ages derived from time series of tritium content in those wells, interpreted by lumped-parameter models. This difference stems mainly from significantly longer travel times of tritium through the unsaturated zone, when compared to the gaseous tracers being used. The results of this study highlight the benefits of using multiple tracing in quantifying timescales of groundwater flow in shallow aquifer systems. PMID- 26863004 TI - Abrupt Decline in Tuberculosis among Foreign-Born Persons in the United States. AB - While the number of reported tuberculosis (TB) cases in the United States has declined over the past two decades, TB morbidity among foreign-born persons has remained persistently elevated. A recent unexpected decline in reported TB cases among foreign-born persons beginning in 2007 provided an opportunity to examine contributing factors and inform future TB control strategies. We investigated the relative influence of three factors on the decline: 1) changes in the size of the foreign-born population through immigration and emigration, 2) changes in distribution of country of origin among foreign-born persons, and 3) changes in the TB case rates among foreign-born subpopulations. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined TB case counts, TB case rates, and population estimates, stratified by years since U.S. entry and country of origin. Regression modeling was used to assess statistically significant changes in trend. Among foreign-born recent entrants (<3 years since U.S. entry), we found a 39.5% decline (-1,013 cases) beginning in 2007 (P<0.05 compared to 2000-2007) and ending in 2011 (P<0.05 compared to 2011-2014). Among recent entrants from Mexico, 80.7% of the decline was attributable to a decrease in population, while the declines among recent entrants from the Philippines, India, Vietnam, and China were almost exclusively (95.5%-100%) the result of decreases in TB case rates. Among foreign-born non recent entrants (>=3 years since U.S. entry), we found an 8.9% decline (-443 cases) that resulted entirely (100%) from a decrease in the TB case rate. Both recent and non-recent entrants contributed to the decline in TB cases; factors contributing to the decline among recent entrants varied by country of origin. Strategies that impact both recent and non-recent entrants (e.g., investment in overseas TB control) as well as those that focus on non-recent entrants (e.g., expanded targeted testing of high-risk subgroups among non-recent entrants) will be necessary to achieve further declines in TB morbidity among foreign-born persons. PMID- 26863005 TI - Factors Influencing Dislodgeable 2, 4-D Plant Residues from Hybrid Bermudagrass (Cynodon dactylon L. x C. transvaalensis) Athletic Fields. AB - Research to date has confirmed 2,4-D residues may dislodge from turfgrass; however, experiments have not been conducted on hybrid bermudagrass (Cynodon dactylon L. x C. transvaalensis), the most common athletic field turfgrass in subtropical climates. More specifically, previous research has not investigated the effect of post-application irrigation on dislodgeable 2,4-D residues from hybrid bermudagrass and across turfgrass species, research has been nondescript regarding sample time within a d (TWD) or conducted in the afternoon when the turfgrass canopy is dry, possibly underestimating potential for dislodgement. The effect of irrigation and TWD on 2,4-D dislodgeability was investigated. Dislodgeable 2,4-D amine was reduced > 300% following irrigation. From 2 to 7 d after treatment (DAT), <= 0.5% of applied 2,4-D was dislodged from irrigated turfgrass, while <= 2.3% of applied 2,4-D was dislodged when not irrigated. 2,4-D dislodgeability decreased as TWD increased. Dislodgeable 2,4-D residues declined to < 0.1% of the applied at 1 DAT- 13:00, and increased to 1 to 3% of the applied 2 DAT- 5:00, suggesting 2,4-D re-suspended on treated turfgrass vegetation overnight. In conclusion, irrigating treated turfgrass reduced dislodgeable 2,4 D. 2,4-D dislodgeability increased as TWD decreased, which was attributed to non precipitation climatic conditions favoring turfgrass canopy wetness. This research will improve turfgrass management practices and research designed to minimize human 2,4-D exposure. PMID- 26863006 TI - Comparison of Long-Term Outcomes of Postmastectomy Radiotherapy between Breast Cancer Patients with and without Immediate Flap Reconstruction. AB - PURPOSE: To compare the long-term clinical outcomes of postmastectomy radiotherapy (PMRT) between breast cancer patients with and without immediate transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. METHODS: The study included 492 patients with stage II or III breast cancer who underwent modified radical mastectomy (MRM) and chemotherapy followed by PMRT between 1997 and 2011. Cox regression model and Kaplan-Meier curves were calculated, and the log-rank test was used to evaluate the differences between overall and disease free survival rates in the 2 groups. RESULTS: Among 492 patients, 213 patients had immediate TRAM flap reconstruction. The mean follow-up was 7.2 years (range, 11-191 months). The 5-year and 10-year disease free survival rates were 81% and 76% for the TRAM flap group and 78% and 73% for the non-flap group. The 5-year and 10-year overall survival rates were 89% and 73% for the TRAM flap group and 83% and 74% for the non-flap group. CONCLUSIONS: There exists no statistically significant difference in the rates of local recurrence, distant metastasis, disease-free and overall survival when comparing immediate TRAM flap reconstruction with no reconstruction. Our results suggest that immediate TRAM flap reconstruction does not compromise long term clinical outcomes in breast cancer patients requiring PMRT. PMID- 26863007 TI - Personality Traits of Suicidality Are Associated with Premenstrual Syndrome and Premenstrual Dysphoric Disorder in a Suicidal Women Sample. AB - OBJECTIVE: Both Premenstrual Syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD) might increase the risk of suicidal behavior. The aim of this study was to assess the relationship between personality dimensions specifically involved in suicidal vulnerability and PMS/PMDD. METHOD: We collected data from 232 women consecutively hospitalized after a suicide attempt. We examined the relationship between impulsivity, aggressiveness/hostility, hopelessness, trait anger, affect intensity, emotional lability, and PMS/PMDD. Notably, we created an algorithm from the shortened Premenstrual Assessment form in order to assess PMDD status. RESULTS: The proportions of PMS and PMDD among female suicide attempters were 50% and 23% respectively. Women with PMS or PMDD were more likely to endorse most of these personality traits to than those without even after controlling for potential confounders. We found an impulsive-aggressive pattern of personality in women with PMS or PMDD, independently from the time of the menstrual cycle. Interestingly, trait anger remained associated with both PMS and PMDD independently of every other personality traits. The higher the anger level, the higher the risk was to suffer from both PMS and PMDD. CONCLUSIONS: This study demonstrates a strong, independent association between PMS/PMDD and trait anger among a representative sample of female suicide attempters. It is of major interest for clinicians in view of addressing a substantial public health problem among women of reproductive age. PMID- 26863008 TI - Association between Social Integration and Health among Internal Migrants in ZhongShan, China. AB - Internal migrants are the individuals who migrate between regions in one country. The number of internal migrants were estimated at 245 million in China in 2013. Results were inconsistent in the literature about the relationship between their health statuses and social integration. The main difference exists on how to measure the social integration and whether health statuses of internal migrants improve with years of residence. To complement the existing literature, this study measured social integration more comprehensively and estimated the internal migrants' health statuses with varying years of residence, and explored the associations between the migrants' social integration and health. We used the data from 2014 Internal Migrant Dynamic Monitoring Survey of Health and Family Planning in ZhongShan, China. Health status was measured from four aspects: self reported health, subjective well-being, perception of stress, mental health. We measured social integration through four dimensions: economy, social communication, acculturation, and self-identity. The analyses used multiple linear regressions to examine the associations between self-reported health, subjective well-being, and perception of stress, mental health and social integration. The analytical sample included 1,999 households of the internal migrants and 1,997 local registered households, who were permanent residents in ZhongShan. Among the internal migrants, Adults in the labor force, who were aged 25 to 44 years old, accounted for 91.2% of the internal migrant population, while 74.6% of the registered population were in that age group. Median residential time among migrants was 2.8 (1.3-6.2) years, and 20.2% of them were migrating in the same Guangdong province. Except for mental health, other health statuses among migrants had significant differences compared with local registered population, e.g. self-reported health was better, but subjective well-being was worse. However, these health measurements were improved with more years of residence. Moreover, our results show that two aspects of social integration, economic integration and self-identity, were significantly associated with health status. Subjective feeling of relative social status levels were more associated with health, which prompted the attention to social fairness and the creation of a fair and respectful culture. More interventions could be experimented, such as encouraging internal migrants to participate in community activities more actively, educating local registered residents to treat internal migrants more equally, and developing self-identity among internal migrants. Better social, economic, and cultural environment can benefit internal migrants' health statuses. PMID- 26863009 TI - Heterologous Expression Screens in Nicotiana benthamiana Identify a Candidate Effector of the Wheat Yellow Rust Pathogen that Associates with Processing Bodies. AB - Rust fungal pathogens of wheat (Triticum spp.) affect crop yields worldwide. The molecular mechanisms underlying the virulence of these pathogens remain elusive, due to the limited availability of suitable molecular genetic research tools. Notably, the inability to perform high-throughput analyses of candidate virulence proteins (also known as effectors) impairs progress. We previously established a pipeline for the fast-forward screens of rust fungal candidate effectors in the model plant Nicotiana benthamiana. This pipeline involves selecting candidate effectors in silico and performing cell biology and protein-protein interaction assays in planta to gain insight into the putative functions of candidate effectors. In this study, we used this pipeline to identify and characterize sixteen candidate effectors from the wheat yellow rust fungal pathogen Puccinia striiformis f sp tritici. Nine candidate effectors targeted a specific plant subcellular compartment or protein complex, providing valuable information on their putative functions in plant cells. One candidate effector, PST02549, accumulated in processing bodies (P-bodies), protein complexes involved in mRNA decapping, degradation, and storage. PST02549 also associates with the P-body resident ENHANCER OF mRNA DECAPPING PROTEIN 4 (EDC4) from N. benthamiana and wheat. We propose that P-bodies are a novel plant cell compartment targeted by pathogen effectors. PMID- 26863010 TI - Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography. AB - PURPOSE: To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT). METHODS: A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS) were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE), axial length, image quality, disc area and rim/disc area ratio (R/D area ratio). RESULTS: For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE). Optical intensity was positively correlated with image quality in all retinal layers (0.5530.05). There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio. CONCLUSIONS: There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis. PMID- 26863011 TI - Interferon-gamma Is a Crucial Activator of Early Host Immune Defense against Mycobacterium ulcerans Infection in Mice. AB - Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing human skin disease associated with the production of the cytotoxic macrolide exotoxin mycolactone. Despite extensive research, the type of immune responses elicited against this pathogen and the effector functions conferring protection against BU are not yet fully understood. While histopathological analyses of advanced BU lesions have demonstrated a mainly extracellular localization of the toxin producing acid fast bacilli, there is growing evidence for an early intra-macrophage growth phase of M. ulcerans. This has led us to investigate whether interferon-gamma might play an important role in containing M. ulcerans infections. In an experimental Buruli ulcer mouse model we found that interferon-gamma is indeed a critical regulator of early host immune defense against M. ulcerans infections. Interferon-gamma knockout mice displayed a faster progression of the infection compared to wild-type mice. This accelerated progression was reflected in faster and more extensive tissue necrosis and oedema formation, as well as in a significantly higher bacterial burden after five weeks of infection, indicating that mice lacking interferon-gamma have a reduced capacity to kill intracellular bacilli during the early intra-macrophage growth phase of M. ulcerans. This data demonstrates a prominent role of interferon-gamma in early defense against M. ulcerans infection and supports the view that concepts for vaccine development against tuberculosis may also be valid for BU. PMID- 26863012 TI - Lactic Acid Production from Pretreated Hydrolysates of Corn Stover by a Newly Developed Bacillus coagulans Strain. AB - An inhibitor-tolerance strain, Bacillus coagulans GKN316, was developed through atmospheric and room temperature plasma (ARTP) mutation and evolution experiment in condensed dilute-acid hydrolysate (CDH) of corn stover. The fermentabilities of other hydrolysates with B. coagulans GKN316 and the parental strain B. coagulans NL01 were assessed. When using condensed acid-catalyzed steam-exploded hydrolysate (CASEH), condensed acid-catalyzed liquid hot water hydrolysate (CALH) and condensed acid-catalyzed sulfite hydrolysate (CASH) as substrates, the concentration of lactic acid reached 45.39, 16.83, and 18.71 g/L by B. coagulans GKN316, respectively. But for B. coagulans NL01, only CASEH could be directly fermented to produce 15.47 g/L lactic acid. The individual inhibitory effect of furfural, 5-hydroxymethylfurfural (HMF), vanillin, syringaldehyde and p hydroxybenzaldehyde (pHBal) on xylose utilization by B. coagulans GKN316 was also studied. The strain B. coagulans GKN316 could effectively convert these toxic inhibitors to the less toxic corresponding alcohols in situ. These results suggested that B. coagulans GKN316 was well suited to production of lactic acid from undetoxified lignocellulosic hydrolysates. PMID- 26863013 TI - Linking Vital Rates of Landbirds on a Tropical Island to Rainfall and Vegetation Greenness. AB - Remote tropical oceanic islands are of high conservation priority, and they are exemplified by range-restricted species with small global populations. Spatial and temporal patterns in rainfall and plant productivity may be important in driving dynamics of these species. Yet, little is known about environmental influences on population dynamics for most islands and species. Here we leveraged avian capture-recapture, rainfall, and remote-sensed habitat data (enhanced vegetation index [EVI]) to assess relationships between rainfall, vegetation greenness, and demographic rates (productivity, adult apparent survival) of three native bird species on Saipan, Northern Mariana Islands: rufous fantail (Rhipidura rufifrons), bridled white-eye (Zosterops conspicillatus), and golden white-eye (Cleptornis marchei). Rainfall was positively related to vegetation greenness at all but the highest rainfall levels. Temporal variation in greenness affected the productivity of each bird species in unique ways. Predicted productivity of rufous fantail was highest when dry and wet season greenness values were high relative to site-specific 5-year seasonal mean values (i.e., relative greenness); while the white-eye species had highest predicted productivity when relative greenness contrasted between wet and dry seasons. Survival of rufous fantail and bridled white eye was positively related to relative dry-season greenness and negatively related to relative wet-season greenness. Bridled white-eye survival also showed evidence of a positive response to overall greenness. Our results highlight the potentially important role of rainfall regimes in affecting population dynamics of species on oceanic tropical islands. Understanding linkages between rainfall, vegetation, and animal population dynamics will be critical for developing effective conservation strategies in this and other regions where the seasonal timing, extent, and variability of rainfall is expected to change in the coming decades. PMID- 26863014 TI - Fungal Ferromanganese Mineralisation in Cretaceous Dinosaur Bones from the Gobi Desert, Mongolia. AB - Well-preserved mycelia of fungal- or saprolegnia-like biota mineralised by ferromanganese oxides were found for the first time in long bones of Late Cretaceous dinosaurs from the Gobi Desert (Nemegt Valley, Mongolia). The mycelia formed a biofilm on the wall of the bone marrow cavity and penetrated the osteon channels of the nearby bone tissue. Optical microscopy, Raman, SEM/EDS, SEM/BSE, electron microprobe and cathodoluminescence analyses revealed that the mineralisation of the mycelia proceeded in two stages. The first stage was early post-mortem mineralisation of the hyphae by Fe/Mn-oxide coatings and microconcretions. Probably this proceeded in a mildly acidic to circumneutral environment, predominantly due to heterotrophic bacteria degrading the mycelial necromass and liberating Fe and Mn sorbed by the mycelia during its lifetime. The second stage of mineralisation, which proceeded much later following the final burial of the bones in an alkaline environment, resulted from the massive precipitation of calcite and occasionally barite on the iron/manganese-oxide coated mycelia. The mineral phases produced by fungal biofilms colonising the interiors of decaying dinosaur bones not only enhance the preservation (fossilisation) of fungal remains but can also be used as indicators of the geochemistry of the dinosaur burial sites. PMID- 26863015 TI - Dialysis-Requiring Acute Kidney Injury in Denmark 2000-2012: Time Trends of Incidence and Prevalence of Risk Factors-A Nationwide Study. AB - INTRODUCTION: Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study. MATERIALS AND METHODS: All patients with dialysis-requiring acute kidney injury were identified between January 1st 2000 and December 31st 2012. By cross-referencing data from national administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis requiring acute kidney injury was evaluated. RESULTS: A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000 and 2012. Crude incidence rate of dialysis-requiring AKI increased from 143 per million (95% confidence interval, 137-144) in 2000 to 366 per million (357-375) in 2006, and remained stable hereafter. Notably, incidence of continuous veno-venous hemodialysis (CRRT) and use of acute renal replacement therapy in elderly >75 years increased substantially from 23 per million (20-26) and 328 per million (300-355) in 2000, to 213 per million (206-220) and 1124 per million (1076-1172) in 2012, respectively. Simultaneously, patient characteristics and demographics shifted towards increased age and comorbidity. CONCLUSIONS: Although growth in crude incidence rate of dialysis-requiring AKI stabilized in 2006, continuous growth in use of CRRT, and acute renal replacement therapy of elderly patients >75 years, was observed. Our results indicate an underlying shift in clinical paradigm, as opposed to unadulterated growth in incidence of dialysis-requiring AKI. PMID- 26863017 TI - New Proposal of Setal Homology in Schizomida and Revision of Surazomus (Hubbardiidae) from Ecuador. AB - The homology of three somatic systems in Schizomida is studied yielding the following results: (1) proposal of homology and chaetotaxy of abdominal setae in Surazomus; (2) revision of the cheliceral chaetotaxy in Schizomida, with suggestion of new homology scheme between Hubbardiidae and Protoschizomidae, description of a new group of setae in Hubbardiinae (G7), and division of setae group 5 in two subgroups, G5A and G5B; (3) proposal of segmental homology between trimerous and tetramerous female flagellum in Hubbardiinae with association of segment III of tri-segmented species to segments III + IV of tetra-segmented species. Considerations about the dorsal microsetae on the male flagellum are made. The genus Surazomus in Ecuador is revised. The sympatric species Surazomus palenque sp. nov. and S. kitu sp. nov. (Ecuador, Pichincha) are described and illustrated. The female of S. cuenca (Rowland and Reddell, 1979) is described, with two new distributional records for the species. Surazomus cumbalensis (Kraus, 1957) is recorded for the first time from Ecuador (Pichincha). PMID- 26863018 TI - A modified olanzapine regimen for the prevention of chemotherapy-induced nausea and vomiting. AB - BACKGROUND: At Kaiser Permanente Antioch and Walnut Creek Cancer Centers, a modified olanzapine regimen is used to prevent chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). OBJECTIVE: To determine if an olanzapine, ondansetron, dexamethasone (OOD) regimen is noninferior to a fosaprepitant, ondansetron, dexamethasone (FOD) regimen in preventing CINV in patients receiving HEC. METHODS: This retrospective cohort study compared the rates of CINV in patients who were treated with HEC and received either the OOD or FOD regimen. Electronic medical records were assessed for documented reports of CINV. 148 patients were included in this study. RESULTS: Complete response (CR), defined as no emesis after Cycle 1 of HEC, in patients receiving the OOD regimen was 95.7% in the acute phase, 94.3% in the delayed phase, and 92.9% overall. CR in patients receiving the FOD regimen was 98.7% in the acute phase, 89.7% in the delayed phase, and 89.7% overall. The percentage of patients who had no nausea on the OOD regimen was 87.1 in the acute phase, 75.5 in the delayed phase, and 71.4 overall, compared with 78.2 in the acute phase, 62.8 in the delayed phase, and 62.7 overall in patients on the FOD regimen. LIMITATIONS: This study was limited by its retrospective, nonrandomized design, and short follow-up period. This study did not assess adverse effects from the antiemetic regimens. CONCLUSIONS: A modified olanzapine regimen is noninferior to a standard fosaprepitant regimen in regard to CR in showing improved control of CINV. In addition, the use of the olanzapine regimen reduces patient exposure to corticosteroids and the risk of associated side effects, and it is significantly more cost effective, compared with the fosaprepitant regimen. PMID- 26863016 TI - Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients. AB - BACKGROUND: Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. METHODS: Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. RESULTS: Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT, RAB11B and CSRP2 (p>0.05), two, SPOP and ZNF671, close to statistical significance (p = 0.051 and 0.076). CONCLUSIONS: We provide evidence of an inflammation-specific autoantibody profile and confirm the expression of corresponding autoantigens in prostate tissue. This supports evaluation of autoantibodies as non-invasive markers for prostate inflammation. PMID- 26863019 TI - Caregivers' attitudes toward promoting exercise among patients with late-stage lung cancer. AB - BACKGROUND: The benefits of exercise, even at low intensity levels, in improving overall health, psychological well-being, and quality of life in patients with cancer have been well documented. However, few patients are involved in formal exercise programs, and little is known about the factors that motivate those who do participate. Although it has not been well assessed, it stands to reason that spousal and family support is an important determinant of cancer patients' adoption of, and adherence to, an exercise program. OBJECTIVE: To characterize attitudes among the family caregivers of patients with late-stage lung cancer about their role in promoting exercise. METHODS: 20 adult family caregivers of patients with stage IIIB or IV non-small-cell lung cancer were asked during semi structured interviews about their views on the role of exercise in "fighting cancer," whether with respect to survival, health, psychological well-being, or overall quality of life; their ability to encourage patients to exercise; and their receptivity to getting exercise instructions from health care providers. FINDINGS: Family caregivers viewed exercise as important in fighting cancer. Past exercise patterns and lifestyle were important considerations, with some family caregivers who had not previously exercised considering household activities sufficient for promoting fitness. Family caregivers emphasized the importance of knowing the established boundaries of their relationships and respecting patients' autonomy. Caregivers generally thought that direction from health care providers to exercise would more likely result in meaningful behavioral change for patients. LIMITATIONS: The participants were recruited from a quaternary medical center and restricted to those with lung cancer, which may limit the generalizability of the findings to other settings or cancers. CONCLUSIONS AND INTERPRETATION: Family caregivers believe that exercise is important for patients, but feel constrained in their willingness and ability to promote exercise behaviors because of the established boundaries of their relationships. They have mixed opinions about the utility of exercise promotion by health care providers. Family caregivers are ambivalent about promoting exercise for patients with advanced cancer. Nonjudgmental assessment of patients' past exercise preferences and established relationship boundaries should inform clinical judgment about the utility of engaging family caregivers in the promotion of exercise. PMID- 26863020 TI - Impact of inpatient radiation on length of stay and health care costs. AB - BACKGROUND: Health care costs are rising. Identifying areas for health care utilization savings may reduce costs. OBJECTIVE: To identify oncology patients receiving inpatient radiotherapy with the purpose of measuring length of stay (LoS) and hospital charges. METHODS: During July 2013 the oncology service physicians at Mount Sinai Medical Center in New York City were surveyed daily to identify patients receiving inpatient radiation. Actual LoS, acuity LoS were determined from the chart review. Expected LoS was calculated using the University Healthsystem Consortium database. Charges associated with actual LoS, acuity LoS, and expected LoS were then reported. Actual and expected LoS were compared for inpatient radiotherapy and nonradiotherapy groups. RESULTS: 7 patients were identified as having remained in the hospital to receive radiation treatment. In that cohort, the average actual LoS and charges per patient were 40.1 and $48,724, compared with acuity LoS and charges of 25.6 days and $34,089 and expected LoS and charges of 7.7 days and $10,028. Mean LoS and charges attributed to radiation alone amounted to 11 days and $12,514. The mean actual LoS of oncology patients admitted during the same time period who did not receive radiation was 6.7 days, compared with 40.1 days for patients who received radiation (?? < .0001). LIMITATIONS: Inability to access actual reimbursement data prevented exact cost calculations, small sample size, and single-institution focus. CONCLUSIONS: Delivery of radiation therapy during inpatient hospitalization extends LoS and contributes to higher health care costs. Methods to facilitate the delivery of outpatient radiotherapy may result in cost savings. PMID- 26863021 TI - Difference in the timing of cessation of palliative chemotherapy between patients with incurable cancer receiving therapy only in a local hospital and those transitioned from a tertiary medical center to a local hospital. AB - BACKGROUND: It is important to know when to decide to end palliative chemotherapy (PC) for the quality of life of patients. However, there is currently no clear agreement on when to terminate PC. OBJECTIVES: To determine whether the difference of the period between the completion of PC and death affects patients' trajectory of supportive care near end of life. METHODS: This retrospective study included 52 adult patients with incurable cancer who had received PC and who were referred to our palliative care team and died in our local hospital between July 2011 and June 2014. Group A comprised patients who received anticancer therapy such as surgery and PC only in our hospital and eventually died there. Group B comprised patients who were transitioned to our hospital from tertiary medical centers after cessation of PC. RESULTS: 17 of 22 patients (77%) in Group A conveyed the intention of continuing PC in the first interview with a physician of the palliative care team, whereas 4 of 30 patients (13%) in Group B conveyed a similar intention. The patients in Group B stopped PC a median of 43 days earlier than did the patients in Group A (?? < .0001). CONCLUSIONS: These data showed that more patients in Group A wanted to continue PC and had a shorter interval between last PC and death. Change in the hospital where the patients are given supportive care might contribute to the cessation of futile PC at an appropriate time. PMID- 26863022 TI - Treatment-related MDS/AML in a patient after treatment for large-cell neuroendocrine lung cancer. AB - Secondary leukemia is a common late complication after exposure to cancer therapies such as chemotherapy and radiotherapy. With the increase in the overall survival of cancer patients over the past 3 decades, treatment-related malignant neoplasms have increased in incidence. Secondary leukemias due to breast cancer and Hodgkin lymphoma have been studied in detail, but to our knowledge only a few case studies have reported secondary leukemias with previous lung cancer.1-4 Lung cancer is the leading cause of cancer death in the United States.5 Since the overall survival (OS) as well as the progression-free survival (PFS) of lung cancer has improved, secondary malignancies, which are usually aggressive and have a poor prognosis, have become a common occurrence among survivors. The use of concurrent chemo-radiotherapy could increase the risk for secondary cancers. Here we report the case of a patient who developed treatment-related acute myelogenous leukemia (t-AML) with a likely prior myelodysplasia (t-MDS) after receiving combined chemo-radiotherapy for lung cancer. PMID- 26863023 TI - Cultural Adaptation of the Portuguese Version of the "Sniffin' Sticks" Smell Test: Reliability, Validity, and Normative Data. AB - The cross-cultural adaptation and validation of the Sniffin'Sticks test for the Portuguese population is described. Over 270 people participated in four experiments. In Experiment 1, 67 participants rated the familiarity of presented odors and seven descriptors of the original test were adapted to a Portuguese context. In Experiment 2, the Portuguese version of Sniffin'Sticks test was administered to 203 healthy participants. Older age, male gender and active smoking status were confirmed as confounding factors. The third experiment showed the validity of the Portuguese version of Sniffin'Sticks test in discriminating healthy controls from patients with olfactory dysfunction. In Experiment 4, the test-retest reliability for both the composite score (r71 = 0.86) and the identification test (r71 = 0.62) was established (p<0.001). Normative data for the Portuguese version of Sniffin'Sticks test is provided, showing good validity and reliability and effectively distinguishing patients from healthy controls with high sensitivity and specificity. The Portuguese version of Sniffin'Sticks test identification test is a clinically suitable screening tool in routine outpatient Portuguese settings. PMID- 26863024 TI - Ratiometric Imaging Using a Single Dye Enables Simultaneous Visualization of Rac1 and Cdc42 Activation. AB - Biosensors that report endogenous protein activity in vivo can be based on environment-sensing fluorescent dyes. The dyes can be attached to reagents that bind selectively to a specific conformation of the targeted protein, such that binding leads to a fluorescence change. Dyes that are sufficiently bright for use at low, nonperturbing intracellular concentrations typically undergo changes in intensity rather than the shifts in excitation or emission maxima that would enable precise quantitation through ratiometric imaging. We report here mero199, an environment-sensing dye that undergoes a 33 nm solvent-dependent shift in excitation. The dye was used to generate a ratiometric biosensor of Cdc42 (CRIB199) without the need for additional fluorophores. CRIB199 was used in the same cell with a FRET sensor of Rac1 activation to simultaneously observe Cdc42 and Rac1 activity in cellular protrusions, indicating that Rac1 but not Cdc42 activity was reduced during tail retraction, and specific protrusions had reduced Cdc42 activity. A novel program (EdgeProps) used to correlate localized activation with cell edge dynamics indicated that Rac1 was specifically reduced during retraction. PMID- 26863026 TI - Sequential Hypothesis Testing to Characterise the Learning Curve and Monitor Surgical Performance in Retinal Detachment Surgery. AB - PURPOSE: To characterise the learning curve of primary retinal detachment (RD) repair for trainee surgeons and monitor the outcomes of surgery for established surgeons. PROCEDURES: Primary RD operations were analysed sequentially using the cumulative sum (CUSUM) and the sequential probability ratio test (SPRT). RESULTS: 359 analysed cases of primary RD were audited with a recurrent RD (ReRD) rate of 14.7%. The individual rate of ReRD ranged from 9.4 to 17.4% (p = 0.74). SPRT and CUSUM analyses showed that ReRD occurred at random when operated by senior surgeons but a learning curve was discernible for junior surgeons. There was a trend for a higher proportion of ReRD caused by untreated breaks in cases operated by junior surgeons (p = 0.75). CONCLUSION: SPRT and CUSUM are useful methods to monitor surgical outcomes and should be included in audits of sequential operations such as RD. Trainee surgeons experience a quantifiable learning curve. PMID- 26863025 TI - A Screen for Modifiers of Cilia Phenotypes Reveals Novel MKS Alleles and Uncovers a Specific Genetic Interaction between osm-3 and nphp-4. AB - Nephronophthisis (NPHP) is a ciliopathy in which genetic modifiers may underlie the variable penetrance of clinical features. To identify modifiers, a screen was conducted on C. elegans nphp-4(tm925) mutants. Mutations in ten loci exacerbating nphp-4(tm925) ciliary defects were obtained. Four loci have been identified, three of which are established ciliopathy genes mks-1, mks-2, and mks-5. The fourth allele (yhw66) is a missense mutation (S316F) in OSM-3, a kinesin required for cilia distal segment assembly. While osm-3(yhw66) mutants alone have no overt cilia phenotype, nphp-4(tm925);osm-3(yhw66) double mutants lack distal segments and are dye-filling (Dyf) and osmotic avoidance (Osm) defective, similar to osm 3(mn357) null mutants. In osm-3(yhw66) mutants anterograde intraflagellar transport (IFT) velocity is reduced. Furthermore, expression of OSM-3(S316F)::GFP reduced IFT velocities in nphp-4(tm925) mutants, but not in wild type animals. In silico analysis indicates the S316F mutation may affect a phosphorylation site. Putative phospho-null OSM-3(S316F) and phospho-mimetic OSM-3(S316D) proteins accumulate at the cilia base and tip respectively. FRAP analysis indicates that the cilia entry rate of OSM-3(S316F) is slower than OSM-3 and that in the presence of OSM-3(S316F), OSM-3 and OSM-3(S316D) rates decrease. In the presence OSM-3::GFP or OSM-3(S316D)::GFP, OSM-3(S316F)::tdTomato redistributes along the cilium and accumulates in the cilia tip. OSM-3(S316F) and OSM-3(S316D) are functional as they restore cilia distal segment formation in osm-3(mn357) null mutants; however, only OSM-3(S316F) rescues the osm-3(mn357) null Dyf phenotype. Despite rescue of cilia length in osm-3(mn357) null mutants, neither OSM-3(S316F) nor OSM-3(S316D) restores ciliary defects in nphp-4(tm925);osm-3(yhw66) double mutants. Thus, these OSM-3 mutations cause NPHP-4 dependent and independent phenotypes. These data indicate that in addition to regulating cilia protein entry or exit, NPHP-4 influences localization and function of a distal ciliary kinesin. Moreover, data suggest human OSM-3 homolog (Kif17) could act as a modifying locus affecting disease penetrance or expressivity in NPHP patients. PMID- 26863027 TI - How the Pathogenic Fungus Alternaria alternata Copes with Stress via the Response Regulators SSK1 and SHO1. AB - The tangerine pathotype of Alternaria alternata is a necrotrophic fungal pathogen causing brown spot disease on a number of citrus cultivars. To better understand the dynamics of signal regulation leading to oxidative and osmotic stress response and fungal infection on citrus, phenotypic characterization of the yeast SSK1 response regulator homolog was performed. It was determined that SSK1 responds to diverse environmental stimuli and plays a critical role in fungal pathogenesis. Experiments to determine the phenotypes resulting from the loss of SSK1 reveal that the SSK1 gene product may be fulfilling similar regulatory roles in signaling pathways involving a HOG1 MAP kinase during ROS resistance, osmotic resistance, fungicide sensitivity and fungal virulence. The SSK1 mutants display elevated sensitivity to oxidants, fail to detoxify H2O2 effectively, induce minor necrosis on susceptible citrus leaves, and displays resistance to dicarboximide and phenylpyrrole fungicides. Unlike the SKN7 response regulator, SSK1 and HOG1 confer resistance to salt-induced osmotic stress via an unknown kinase sensor rather than the "two component" histidine kinase HSK1. SSK1 and HOG1 play a moderate role in sugar-induced osmotic stress. We also show that SSK1 mutants are impaired in their ability to produce germ tubes from conidia, indicating a role for the gene product in cell differentiation. SSK1 also is involved in multi-drug resistance. However, deletion of the yeast SHO1 (synthetic high osmolarity) homolog resulted in no noticeable phenotypes. Nonetheless, our results show that A. alternata can sense and react to different types of stress via SSK1, HOG1 and SKN7 in a cooperative manner leading to proper physiological and pathological functions. PMID- 26863028 TI - Altered Functional Connectivity of the Insula and Nucleus Accumbens in Internet Gaming Disorder: A Resting State fMRI Study. AB - AIMS: A possible addiction mechanism has been represented by altered functional connectivity (FC) in the resting state. The aim of this study was to evaluate the FCs of the insula and nucleus accumbens among subjects with Internet gaming disorder (IGD). METHODS: We recruited 30 males with IGD and 30 controls and evaluated their FC using functional magnetic imaging scanning under resting, a state with relaxation, closed eyes, with inducement to think of nothing systematically, become motionless, and instructed not to fall asleep. RESULTS: Subjects with IGD had a lower FC with the left insula over the left dorsolateral prefrontal cortex (DLPFC) and orbital frontal lobe and a higher FC with the insula with the contralateral insula than controls. The inter-hemispheric insula connectivity positively correlated with impulsivity. Further, they had lower FC with the left nucleus accumbens over the left DLPFC and with the right nucleus accumbens over the left DLPFC, and insula and a higher FC with that over the right precuneus. CONCLUSION: The elevated inter-hemispheric insula FC is found to be associated with impulsivity and might explain why it is involved in IGD. The attenuated frontostriatal suggests that the emotion-driven gaming urge through nucleus accumbens could not be well regulated by the frontal lobe of subjects with IGD. PMID- 26863030 TI - On the Road (to a Cure?)--Stem-Cell Tourism and Lessons for Gene Editing. PMID- 26863029 TI - Lipopolysaccharide (LPS) Promotes Apoptosis in Human Breast Epithelial * Breast Cancer Hybrids, but Not in Parental Cells. AB - Toll-like receptors (TLRs) belong to the group of pathogen recognition receptors known to play a crucial role in the innate immune system. In cancer, TLR expression is still debated controversially due to contradictory results reporting that both induction of apoptosis as well as tumor progression could depend on TLR signaling, whereby recent data rather indicate a pro-tumorigenic effect. The biological phenomenon of cell fusion has been associated with cancer progression due to findings revealing that fusion-derived hybrid cells could exhibit properties like an increased metastatogenic capacity and an increased drug resistance. Thus, M13MDA435 hybrid cell lines, which derived from spontaneous fusion events between human M13SV1-EGFP-Neo breast epithelial cells and human MDA-MB-435-Hyg breast cancer cells, were investigated. Cultivation of cells in the presence of the TLR4 ligand LPS potently induced apoptosis in all hybrid clones, but not in parental cells, which was most likely attributed to differential kinetics of the TLR4 signal transduction cascade. Activation of this pathway concomitant with NF-kappaB nuclear translocation and TNF-alpha expression was solely observed in hybrid cells. However, induction of LPS mediated apoptosis was not TNF-alpha dependent since TNF-alpha neutralization was not correlated to a decreased amount of dead cells. In addition to TNF-alpha, LPS also caused IFN beta expression in hybrid clones 1 and 3. Interestingly, hybrid clones differ in the mode of LPS induced apoptosis. While neutralization of IFN-beta was sufficient to impair the LPS induced apoptosis in M13MDA435-1 and -3 hybrids, the amount of apoptotic M13MDA435-2 and -4 hybrid cells remained unchanged in the presence of neutralizing IFN-beta antibodies. In summary, the fusion of non-LPS susceptible parental human breast epithelial cells and human breast cancer cells gave rise to LPS susceptible hybrid cells, which is in view with the cell fusion hypothesis that hybrid cells could exhibit novel properties. PMID- 26863032 TI - Delayed Treatment with Sodium Hydrosulfide Improves Regional Blood Flow and Alleviates Cecal Ligation and Puncture (CLP)-Induced Septic Shock. AB - Cecal ligation and puncture (CLP)-induced sepsis is a serious medical condition, caused by a severe systemic infection resulting in a systemic inflammatory response. Recent studies have suggested the therapeutic potential of donors of hydrogen sulfide (H2S), a novel endogenous gasotransmitter and biological mediator in various diseases. The aim of the present study was to assess the effect of H2S supplementation in sepsis, with special reference to its effect on the modulation of regional blood flow. We infused sodium hydrosulfide (NaHS), a compound that produces H2S in aqueous solution (1, 3, or 10 mg/kg/h, for 1 h at each dose level) in control rats or rats 24 h after CLP, and measured blood flow using fluorescent microspheres. In normal control animals, NaHS induced a characteristic redistribution of blood flow, and reduced cardiac, hepatic, and renal blood flow in a dose-dependent fashion. In contrast, in rats subjected to CLP, cardiac, hepatic, and renal blood flow was significantly reduced; infusion of NaHS (1 mg/kg/h and 3 mg/kg/h) significantly increased organ blood flow. In other words, the effect of H2S on regional blood flow is dependent on the status of the animals (i.e., a decrease in blood flow in normal controls, but an increase in blood flow in CLP). We have also evaluated the effect of delayed treatment with NaHS on organ dysfunction and the inflammatory response by treating the animals with NaHS (3 mg/kg) intraperitoneally (i.p.) at 24 h after the start of the CLP procedure; plasma levels of various cytokines and tissue indicators of inflammatory cell infiltration and oxidative stress were measured 6 h later. After 24 h of CLP, glomerular function was significantly impaired, as evidenced by markedly increased (over 4-fold over baseline) blood urea nitrogen and creatinine levels; this increase was also significantly reduced by treatment with NaHS. NaHS also attenuated the CLP-induced increases in malondialdehyde levels (an index of oxidative stress) in heart as well as in liver and myeloperoxidase levels (an index of neutrophil infiltration) in heart and lung. Plasma levels of IL-1beta, IL-5, IL-6, TNF-alpha, and HMGB1 were attenuated by NaHS. Treatment of NaHS at 3 mg/kg i.p. (but not 1 mg/kg or 6 mg/kg), starting 24 h post-CLP, with dosing repeated every 6 h, improved the survival rate in CLP animals. In summary, treatment with 3 mg/kg H2S-when started in a delayed manner, when CLP-induced organ injury, inflammation and blood flow redistribution have already ensued-improves blood flow to several organs, protects against multiple organ failure, and reduces the plasma levels of multiple pro-inflammatory mediators. These findings support the view that H2S donation may have therapeutic potential in sepsis. PMID- 26863033 TI - Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock. AB - The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia, and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here, we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma versus normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections. PMID- 26863034 TI - Grafting of Beads into Developing Chicken Embryo Limbs to Identify Signal Transduction Pathways Affecting Gene Expression. AB - Using chicken embryos it is possible to test directly the effects of either growth factors or specific inhibitors of signaling pathways on gene expression and activation of signal transduction pathways. This technique allows the delivery of signaling molecules at precisely defined developmental stages for specific times. After this embryos can be harvested and gene expression examined, for example by in situ hybridization, or activation of signal transduction pathways observed with immunostaining. In this video heparin beads soaked in FGF18 or AG 1-X2 beads soaked in U0126, a MEK inhibitor, are grafted into the limb bud in ovo. This shows that FGF18 induces expression of MyoD and ERK phosphorylation and both endogenous and FGF18 induced MyoD expression is inhibited by U0126. Beads soaked in a retinoic acid antagonist can potentiate premature MyoD induction by FGF18. This approach can be used with a wide range of different growth factors and inhibitors and is easily adapted to other tissues in the developing embryo. PMID- 26863035 TI - The Complete and Updated "Rotifer Polyculture Method" for Rearing First Feeding Zebrafish. AB - The zebrafish (Danio rerio) is a model organism of increasing importance in many fields of science. One of the most demanding technical aspects of culture of this species in the laboratory is rearing first-feeding larvae to the juvenile stage with high rates of growth and survival. The central management challenge of this developmental period revolves around delivering highly nutritious feed items to the fish on a nearly continuous basis without compromising water quality. Because larval zebrafish are well-adapted to feed on small zooplankton in the water column, live prey items such as brachionid rotifers, Artemia, and Paramecium are widely recognized as the feeds of choice, at least until the fish reach the juvenile stage and are able to efficiently feed on processed diets. This protocol describes a method whereby newly hatched zebrafish larvae are cultured together with live saltwater rotifers (Brachionus plicatilis) in the same system. This polyculture approach provides fish with an "on-demand", nutrient-rich live food source without producing chemical waste at levels that would otherwise limit performance. Importantly, because the system harnesses both the natural high productivity of the rotifers and the behavioral preferences of the fish, the labor involved with maintenance is low. The following protocol details an updated, step-by-step procedure that incorporates rotifer production (scalable to any desired level) for use in a polyculture of zebrafish larvae and rotifers that promotes maximal performance during the first 5 days of exogenous feeding. PMID- 26863036 TI - Report of a 14-Year-Old Boy Whose Testosterone Level Decreased After Starting on Methylphenidate. PMID- 26863037 TI - Effect of sternoclavicular joint mobilization on pain and function in a patient with massive supraspinatus tear. AB - Massive irreparable rotator cuff tears can be difficult to treat conservatively, especially when the patient has multiple comorbidities. Although there is evidence to support interventions aimed at the spine, there is paucity in the literature describing interventions to the sternoclavicular joint (SCJ) in individuals with rotator cuff pathology. A 57-year-old female with multiple comorbidities and a body mass index of 59 was referred to physical therapy with a 4-month history of right shoulder pain, significant functional limitations, and magnetic resonance imaging (MRI), demonstrating a full-thickness supraspinatus tear. She presented initially with active shoulder flexion range of motion (ROM) 0-80 degrees , numeric pain rating scale (NPRS) 7/10, and QuickDASH 65.9%. After six physical therapy sessions, the patient had plateaued with improvements in pain and ROM. SCJ mobilizations at visit 7 immediately improved pain, active ROM, and subjective reports of function. The patient was discharged after 13 visits with increased active shoulder flexion ROM to 0-170 degrees , NPRS 1/10, QuickDASH 31.8%, and Global Rating of Change (GROC) +5. This case highlights the successful conservative treatment of an individual with an irreparable rotator cuff tear and numerous comorbidities by using a multimodal approach including SCJ mobilizations. PMID- 26863038 TI - Assessing the Effectiveness of Arnica montana and Rhododendron tomentosum (Ledum palustre) in the Reduction of Ecchymosis and Edema After Oculofacial Surgery: Preliminary Results. AB - PURPOSE: The purpose of this study was to provide preliminary data on the potential effectiveness of the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) in reducing postoperative ecchymosis and edema in a select population of healthy volunteers after oculofacial surgery. METHODS: This retrospective review examined the postoperative course of healthy volunteers using topical Arnica and Ledum after undergoing common oculofacial procedures, including blepharoplasty, browpexy, and rhinoplasty, in the hands of 4 surgeons at tertiary referral centers from July 1, 2012 to December 31, 2012 using medical records review. Each patient included had used topical hydrogel pads (OcuMend, Cearna Inc., Chicago, IL) containing Arnica 50 M (10) 50% and Ledum 50 M (10). The pads were applied bilaterally after surgery through postoperative day 6. At each postoperative visit, the patients were evaluated by their respective surgeons and assigned a subjective physician-patient rating score comparing each patient's observed healing compared with expected healing if not using Arnica/Ledum. Photographs of patients undergoing equivalent procedures, but not using Arnica/Ledum were used as controls for comparison. Physician patient rating scores were categorical: markedly accelerated healing defined as approximately 7 days ahead of expected, accelerated healing, defined as <7 days ahead of expected, and no appreciable difference from expected. The proportion of patients with each physician-patient rating score was calculated for postoperative days 1 to 2, 3 to 5, 6 to 8, and overall. Difference of proportions was calculated with 95% confidence intervals using Newcombe unpaired difference comparison of proportions. Photographs documenting the clinical progression of selected patients are provided. RESULTS: A total of 27 patients (16 females, 11 males) were included in the study. Age range was 18 to 70 years. The majority of patients were white (52.9%), and underwent blepharoplasty (78.9%). The median duration of follow-up was 7 days, range 1 to 14 days. The proportions of patients with markedly accelerated healing were 38.5% (5 of 13), 85.7% (6 of 7), 60.0% (12 of 20), and 51.9% (14 of 27) at POD 1 to 2, 3 to 5, 6 to 8, and overall, respectively. The proportions of patients with accelerated healing at the same time points were 15.4% (2 of 13), 14.3% (1 of 7), 30.0% (6 of 20), and 37.0% (10 of 27), respectively. The proportions of patients with no appreciable difference at the same time points were 46.2% (6 of 13), 0% (0 of 7), 10.0% (2 of 20), and 11.1% (3 of 27) of patients, respectively. The proportion of patients using Arnica/Ledum with markedly accelerated healing was significantly more than the proportion of those demonstrating no appreciable difference from expected at POD 3 to 5 (85.7% vs. 0%, p = 0.05), POD 6 to 8 (60.0% vs. 10.0%), and overall (51.9% vs. 11.1%, p = 0.05). No adverse effects were reported. CONCLUSIONS: The preliminary results from this study demonstrate that the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) may be effective in reducing postoperative ecchymosis and edema after oculofacial surgery. PMID- 26863039 TI - Changes in Tear Film Characteristics in Patients With Idiopathic Dacryoadenitis. AB - PURPOSE: To evaluate the tear-film meniscus with optical coherence tomography (OCT) in patients with idiopathic dacryoadenitis and to determine its relationships with the clinical tests. METHODS: Sixteen patients with unilateral idiopathic dacryoadenitis were included in the study. Patients with idiopathic dacryoadenitis with affected sites (group 1), with contralateral sites (group 2) and healthy participants (group 3) completed the ocular surface disease index before optical coherence tomography determination of tear meniscus height and tear meniscus area. These were followed by measurements of tear breakup time, fluorescein staining, and Schirmer test. Finally, surgical debulking or incisional biopsies were conducted. RESULTS: Tear meniscus height and tear meniscus area were the lowest in patients with affected sites (group 1) among the 3 groups (p < 0.05). Breakup time was the shortest in group 1 (p < 0.05). In the group 1, breakup time, fluorescein staining score, and histopathological phases were significantly correlated with tear meniscus height and tear meniscus area (p < 0.05). CONCLUSIONS: Tear function was significantly disturbed in idiopathic dacryoadenitis. Tear menisci volumes measured by optical coherence tomography may assess the tearing function in patients with idiopathic dacryoadenitis. PMID- 26863040 TI - Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit. AB - Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist. PMID- 26863041 TI - Positive Effects of Subdermal Lipotransfer on Pig's Upper Eyelid Skin: Mature Adipocytes or Adipose-Derived Stem Cells Alone Contribute Little and Only Cotransplantation of Them Can Generate Benefits. AB - BACKGROUND: Many studies have shown that autologous fat grafting and cell assisted lipotransfer can improve skin quality, with both mature adipocytes (MAs) and adipose-derived stem cells (ADSCs) considered to play a role. However, it is unclear whether transplantation of ADSCs or MAs has the same impact on the overlying skin. METHODS: Nine pigs were divided into 3 equal groups, with lipoaspirates obtained from the porcine dorsum of each pig. Transplant content was injected into the right upper eyelids, while the left eyelids were used as controls. Following cellular isolation, 1 group underwent MA grafting, 1 underwent ADSCs transplantation, and 1 underwent cotransplantation of MAs and ADSCs. Epidermal thickness, epidermal cell proliferation, dermal thickness, collagen content, and arteriole density were examined. RESULTS: While no significant skin changes in the areas examined were noted following MAs or ADSCs transplantations, the cotransplantation of MAs and ADSCs resulted in significant increases in epidermal cell proliferation, dermal thickness, collagen content, and arteriole density. CONCLUSION: Subdermal injection of MAs or ADSCs alone does not significantly impact the overlying skin and the benefits to the skin can only be seen when MAs and ADSCs are cotransplanted; these findings suggest that ADSCs enhanced fat grafting is necessary for the aim of antiaging treatments. PMID- 26863042 TI - Fungus Ball of the Maxillary Sinus Presenting With Epiphora. AB - The authors report a case of fungus ball of the maxillary sinus with bone erosion presenting with epiphora, which was diagnosed after treatment failure using silicone intubation for nasolacrimal duct obstruction. Symptoms of sinus fungus ball are similar to those of chronic bacterial rhinosinusitis, although occasionally asymptomatic. To our knowledge, epiphora has never been reported as a symptom of sinus fungus ball. The purpose of this report is to emphasize the importance of considering sinonasal causes when evaluating epiphora patients, as well as to suggest the use of preoperative CT scans for a more accurate diagnosis and to prevent unnecessary procedures. PMID- 26863043 TI - Intraoperative Instrument Fracture During Endoscopic Dacryocystorhinostomy. PMID- 26863044 TI - Preparation of ZnO Nanorod/Graphene/ZnO Nanorod Epitaxial Double Heterostructure for Piezoelectrical Nanogenerator by Using Preheating Hydrothermal. AB - Well-aligned ZnO nanostructures have been intensively studied over the last decade for remarkable physical properties and enormous applications. Here, we describe a one-step fabrication technique to synthesis freestanding ZnO nanorod/graphene/ZnO nanorod double heterostructure. The preparation of the double heterostructure is performed by using thermal chemical vapor deposition (CVD) and preheating hydrothermal technique. In addition, the morphological properties were characterized by using the scanning electron microscopy (SEM). The utility of freestanding double heterostructure is demonstrated by fabricating the piezoelectric nanogenerator. The electrical output is improved up to 200% compared to that of a single heterostructure owing to the coupling effect of the piezoelectricity between the arrays of ZnO nanorods on the top and bottom of graphene. This unique double heterostructure have a tremendous potential for applications of electrical and optoelectrical devices where the high number density and specific surface area of nanorod are needed, such as pressure sensor, immuno-biosensor and dye-sensitized solar cells. PMID- 26863045 TI - A Method to Manipulate Surface Tension of a Liquid Metal via Surface Oxidation and Reduction. AB - Controlling interfacial tension is an effective method for manipulating the shape, position, and flow of fluids at sub-millimeter length scales, where interfacial tension is a dominant force. A variety of methods exist for controlling the interfacial tension of aqueous and organic liquids on this scale; however, these techniques have limited utility for liquid metals due to their large interfacial tension. Liquid metals can form soft, stretchable, and shape reconfigurable components in electronic and electromagnetic devices. Although it is possible to manipulate these fluids via mechanical methods (e.g., pumping), electrical methods are easier to miniaturize, control, and implement. However, most electrical techniques have their own constraints: electrowetting-on dielectric requires large (kV) potentials for modest actuation, electrocapillarity can affect relatively small changes in the interfacial tension, and continuous electrowetting is limited to plugs of the liquid metal in capillaries. Here, we present a method for actuating gallium and gallium-based liquid metal alloys via an electrochemical surface reaction. Controlling the electrochemical potential on the surface of the liquid metal in electrolyte rapidly and reversibly changes the interfacial tension by over two orders of magnitude ( 500 mN/m to near zero). Furthermore, this method requires only a very modest potential (< 1 V) applied relative to a counter electrode. The resulting change in tension is due primarily to the electrochemical deposition of a surface oxide layer, which acts as a surfactant; removal of the oxide increases the interfacial tension, and vice versa. This technique can be applied in a wide variety of electrolytes and is independent of the substrate on which it rests. PMID- 26863046 TI - Extended Ciprofloxacin Release Using Vitamin E Diffusion Barrier From Commercial Silicone-Based Soft Contact Lenses. AB - OBJECTIVES: Ciprofloxacin (Cipro) is an antibiotic, widely used in form of ophthalmic drops (0.3%) for the treatment of eye infections. In this study, vitamin E was used as a hydrophobic barrier to improve and prolong the amount and time of Cipro release from silicone-based soft contact lenses. METHODS: Three different commercial contact lenses (Air Optix, Biofinity, and Acuvue Oasys) were soaked in vitamin E solutions (0.1 and 0.2 g/mL). The effect of vitamin E on Cipro loading amount and drug releasing profile was evaluated in artificial tear. Swelling properties and diameter changes of the lenses were also investigated in aqueous media in presence and absence of vitamin E. RESULTS: The data indicated that vitamin E, as a hydrophobic barrier, significantly decreased the water content of silicone-based soft contact lenses. After vitamin E loading, a 5% to 18% increase was observed in lens diameter in the hydrated state, whereas the lens diameter increased by 11% to 23% in the dry state. In all commercial lenses, vitamin E loading in a 0.2-g/mL solution caused a 27.94% to 37.08% increase in Cipro binding. The results indicated that applying vitamin E loading solutions, with 0.1 and 0.2 g/mL concentrations, could effectively enhance Cipro release time from 2 hr (in a pure non-vitamin E-loaded lens) to 14 to 17 and 30 to 33 days, respectively. These values showed an increase by a factor of 168 to 204 and 360 to 396 in Cipro release time after using vitamin E loading solutions with 0.1 and 0.2 g/mL concentrations, respectively, compared with pure non-vitamin E loaded soft contact lenses. CONCLUSIONS: This study indicated that vitamin E acts as an effective hydrophobic barrier, in increasing the Cipro loading capacity of silicone-based contact lenses and prolonging the drug release into the artificial tear. PMID- 26863047 TI - Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo. AB - Numerous gene and cell therapy strategies are being developed for the treatment of neurodegenerative disorders. Many of these strategies use constitutive expression of therapeutic transgenic proteins, and although functional in animal models of disease, this method is less likely to provide adequate flexibility for delivering therapy to humans. Ligand-inducible gene expression systems may be more appropriate for these conditions, especially within the central nervous system (CNS). Mifepristone's ability to cross the blood-brain barrier makes it an especially attractive ligand for this purpose. We describe the production of a mifepristone-inducible vector system for regulated expression of transgenes within the CNS. Our inducible system used a lentivirus-based vector platform for the ex vivo production of mifepristone-inducible murine neural progenitor cells that express our transgenes of interest. These cells were processed through a series of selection steps to ensure that the cells exhibited appropriate transgene expression in a dose-dependent and temporally controlled manner with minimal background activity. Inducible cells were then transplanted into the brains of rodents, where they exhibited appropriate mifepristone-inducible expression. These studies detail a strategy for regulated expression in the CNS for use in the development of safe and efficient gene therapy for neurological disorders. PMID- 26863048 TI - Enhancing Documentation of Pressure Ulcer Prevention Interventions: A Quality Improvement Strategy to Reduce Pressure Ulcers. AB - Prevention of hospital-acquired pressure ulcers requires the implementation of evidence-based interventions. A quality improvement project was conducted to provide nurses with data on the frequency with which pressure ulcer prevention interventions were performed as measured by documentation. Documentation reports provided feedback to stakeholders, triggering reminders and reeducation. Intervention reports and modifications to the documentation system were effective both in increasing the documentation of pressure ulcer prevention interventions and in decreasing the number of avoidable hospital-acquired pressure ulcers. PMID- 26863049 TI - Individualized Care in the Radiation Oncology Setting From the Patients' and Nurses' Perspectives. AB - BACKGROUND: Radiation oncology nurses engage in individualized supportive care of people undergoing radiotherapy. A primary nursing/collaborative practice framework guides the delivery of individualized care to patients. OBJECTIVE: The aim of this study was to describe and compare patients' and nurses' perceptions of individualized care in 2 radiotherapy centers. METHODS: This cross-sectional, comparative study collected data from patients (n = 173) undergoing curative radiotherapy and their nurses (n = 30), using the Individualized Care scales: patient and nurse. RESULTS: Moderate to high levels of individual care were perceived by both patients and nurses. More than a third of the item scores for patients reached the more than 4.5 mean score (13/34 [38.2%]), whereby more than half of the items reached this level for nurses (20/34 [58.8%]). The highest scores for both patients and nurses were in the Decisional Control subscales, and the lowest scores were in the Personal Life subscales. Males rated being treated as individuals significantly higher than did females across the majority of subscales. Patients receiving chemotherapy perceived less acknowledgement of individuality overall. Older nurses (46-70 years) reported acknowledging and supporting patient individuality more than did younger nurses. Nurses perceived greater individualized care than patients for the Personal Life scales (A: p = .001); (B: p = .001) and in the acknowledgement of Decisional Control (p = .001). CONCLUSION: A moderate level of individualized nursing care was perceived by the largely outpatient cohort of patients undergoing radiotherapy. IMPLICATIONS FOR PRACTICE: The model of care in these departments may contribute to patient individuality. Further work into gender differences and those receiving chemotherapy may improve care for these patients. PMID- 26863050 TI - Japanese Nurses' Perceptions Toward Tobacco Use Intervention for Hospitalized Cancer Patients Who Entered End of Life. AB - BACKGROUND: Smoking patients who are admitted to a smoke-free hospital often experience nicotine withdrawal. Control of withdrawal symptoms in hospitalized patients with terminal illness by nurses may be important to end-of-life care. OBJECTIVE: The aims of this study were to assess Japanese nurses' perceptions toward providing a tobacco use intervention to hospitalized cancer patients who are receiving palliative and end-of-life care and to investigate demographic factors associated with a positive perception. METHODS: We conducted a cross sectional survey of 1955 nurses at 6 selected hospitals in Japan. Multivariate logistic regression analysis was performed using age, workplace, length of nursing education, primary position, academic certification, having received instruction on smoking cessation programs at their nursing school, having attended lectures on smoking cessation programs at his/her hospital, and smoking status as potential independent variables. RESULTS: The proportion of nurses who had a positive perception toward providing a tobacco use intervention to hospitalized cancer patients receiving end-of-life care was only 16% to 20% at each hospital. Experience of having received instruction on tobacco use interventions while in nursing school was significantly associated with having a positive perception toward providing a tobacco use intervention for such patients. CONCLUSIONS: Most of the Japanese nurses had a conservative perception toward providing a tobacco use intervention for cancer patients who are receiving end-of-life care. Having received instruction on interventions while in a nursing school was likely to yield a positive perception. IMPLICATIONS FOR PRACTICE: It is important to introduce instruction on tobacco use interventions for patients with terminal-stage cancer in the standard curriculum of nursing schools in Japan. PMID- 26863051 TI - Cancer Nursing Research Output in Africa 2005 to 2014: An Integrative Review. AB - BACKGROUND: This study is the first review of African cancer nursing research as only 1 review focusing on South Africa was conducted in the past decade. OBJECTIVE: The aim of this study was to identify, summarize, and synthesize the findings from previous independent studies conducted by nurses in Africa. METHODS: The terms cancer nursing and oncology nursing and Africa were used to search PubMed, CINAHL, Web of Science, SA e-publications, and Scopus. Studies reporting research conducted in an African setting, coauthored by a nurse affiliated with an African institution and published between January 1, 2005, and December 31, 2014, in English were included. A data extraction sheet captured the data. RESULTS: A potential 536 articles for possible inclusion were identified. Fifty met the inclusion requirements. Cancer in women (78%; n = 39) and prevention and early detection (62%; n = 31) were most commonly investigated. The work was primarily quantitative and collected data on some knowledge aspect from women in the community. Most of the studies (96%; n = 48) did not meet the criteria of high-quality work. CONCLUSIONS: Africa's nurses have improved their research output in the field of cancer nursing considerably. Research focusing on the most prevalent cancers, the treatment, the patient living with cancer, the family, extended family, and community is lacking, as is work focusing on pain and other symptoms. IMPLICATIONS FOR NURSING PRACTICE: Nurses in practice should assist nurse researchers to address the identified knowledge gaps to develop cancer nursing science and practice tailored to meet the unique needs of Africa. PMID- 26863052 TI - Coping Strategies at the Time of Diagnosis and Quality of Life 2 Years Later: A Study in Primary Cutaneous Melanoma Patients. AB - BACKGROUND: While coping has been found to have time-lagged effects on psychological adjustment in cancer patients, studies addressing this issue are missing in melanoma patients. OBJECTIVE: The aim of this study was to provide more insight into the links between coping strategies at the time of diagnosis and quality of life (QOL) 2 years later in patients with primary cutaneous melanoma. METHODS: Patients who received diagnosis of melanoma (n = 78) were assessed regarding coping strategies within 1 month of diagnosis (T1); their anxiety, depression, control, QOL, and life satisfaction were evaluated 24 months later (T2). Relevant medical and sociodemographic data were collected at T1 and T2. Hierarchical regression analyses were performed. RESULTS: Consistent with the literature, we found that higher positive reframing was associated with greater life satisfaction and that increased behavioral disengagement was related to decreased cognitive functioning. Surprisingly, our results highlighted that higher active coping predicted lower emotional functioning and that greater religious coping was associated with more reports of nausea symptoms. We also noticed that depression was strongly related to QOL beyond the end of interferon alpha therapy. CONCLUSION: The findings of the present study suggest that specific coping strategies may have time-lagged effects on QOL when the treatment is completed. IMPLICATIONS FOR PRACTICE: These findings provide new insights into the coping strategies that could be promoted in coping skills interventions in dermatology units and reveal the significant role of preventive care concerning the posttreatment period. PMID- 26863053 TI - Quality of Life After Hematopoietic Stem Cell Transplantation in Pediatric Survivors: Comparison With Healthy Controls and Risk Factors. AB - BACKGROUND: Hematopoietic stem cell transplantation has prolonged life for children with life-threatening diseases. Quality of life is an essential outcome for evaluating the long-term effects of transplantation. OBJECTIVE: The aims of this study were to compare the quality of life of children posttransplantation to that of healthy peers and explore the variables associated with the quality of life of posttransplant children. METHODS: A cross-sectional study was conducted with 43 pediatric transplantation survivors and 43 age- and sex-matched healthy peers. RESULTS: The mean age of the transplant group was 12.06 years. The mean time since transplant was 3.73 years. After covariate adjustment, there was no difference between posttransplant and healthy children in each domain and overall quality of life, except for physical functioning where the posttransplant children had lower scores than did the healthy group. Chronic graft-versus-host disease was found to be the primary factor associated with poor posttransplant overall quality of life and emotional and social functioning. Sociodemographic variables, symptom distress, and caregiver depression were not correlated with posttransplant quality of life. CONCLUSIONS: The quality of life of pediatric transplantation survivors was comparable to that of healthy peers. IMPLICATIONS FOR PRACTICE: The finding that children after transplant may achieve quality of life similar to their healthy peers is important information for parents to consider as they consider treatment options. For those sick children who cannot regularly attend school, their emotional and social functioning should be closely monitored. PMID- 26863054 TI - Macular Thickness in Myopia: An OCT Study of Young Chinese Patients. AB - PURPOSES: To investigate macular thickness (MT) in young myopic Chinese patients using Spectralis optical coherence tomography (OCT) and to assess its association with gender, axial length (AL), spherical equivalent (SE), and intraocular pressure (IOP). METHODS: Included in this study were 133 myopic Chinese patients, aged 18-30 years. All underwent complete ophthalmic examinations and Spectralis OCT. Inner, central, and outer foveal regions of the macula were measured. RESULTS: The central fovea was the thinnest of the three macular regions (mean thickness, 250.1 +/- 15.3 MUm). Women had consistently thinner MTs than did men, except in the outer superior and inferior areas. Central foveal thickness (CFT) was positively correlated with AL and negatively correlated with SE. In the inner and outer regions, MT was positively correlated with SE. AL was negatively correlated with MT in all quadrants of the inner and outer sectors, but not the inner superior and outer nasal areas. No macular measurement was significantly correlated with age or IOP in either gender. CONCLUSIONS: Variables affecting MT should be considered when evaluating SD-OCT data in young myopic Chinese patients, with and without retinal diseases. PMID- 26863055 TI - Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis. AB - OBJECTIVE: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. METHODS: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. RESULTS: TNFalpha significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1beta also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. CONCLUSION: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model. PMID- 26863056 TI - Malignant Myopericytoma: Report of a New Case and Review of the Literature. AB - Malignant myopericytoma is a rare entity with only 8 cases reported in the English literature. The authors report a case of a 65-year-old man with a slow growing 8-cm nodule on the right arm. Marginal excision was performed, and a diagnosis of malignant myopericytoma was made based on histopathologic and immunohistochemical aspects. These tumors are characterized by a proliferation of round-to-spindle cells of myoid appearance in a concentric perivascular arrangement, along with malignant cytological findings. By immunochemistry, the cells were positive for smooth muscle actin and negative for desmin, cytokeratin AE1/AE3, S100 protein, Melan-A, p63, CD99, bcl-2, CD10, and STAT-6. No membranous expression of type IV collagen was observed. These tumors are associated with aggressive biological behavior and most develops metastases. PMID- 26863057 TI - Bilateral Gigantomastia, Multiple Synchronous Nodular Pseudoangiomatous Stromal Hyperplasia Involving Breast and Bilateral Axillary Accessory Breast Tissue, and Perianal Mammary-Type Hamartoma of Anogenital Mammary-Like Glands: A Case Report. AB - Mammary-type fibroepithelial lesions involving ectopic breast and anogenital region are rare and usually coexist with normal orthotopic breast. We present what we believe to be a unique case of synchronous bilateral gestational gigantomastia resembling fibrous mastopathy, synchronous rapidly growing pregnancy-associated nodular pseudoangiomatous stromal hyperplasia involving right breast and bilateral axillary ectopic breast tissue, and metachronous perianal mammary-type hamartoma involving anogenital mammary-like glands occurring in a 34-year-old patient with facioscapulohumeral muscular dystrophy. Also, we review the literature concerning these lesions. PMID- 26863058 TI - Primary Cutaneous Anaplastic Large-Cell Lymphoma With 6p25.3 Rearrangement in a Cardiac Transplant Recipient: A Case Report and Review of the Literature. AB - Posttransplant lymphoproliferative disorders define an important form of lymphoproliferative disease causally linked with a state of iatrogenic immune dysregulation inherent to the posttransplant setting. Most posttransplant lymphoproliferative disorders are in the context of Epstein-Barr virus-associated B-cell lymphoproliferative disease, most notably diffuse large-cell B-cell lymphoma. A less common variant falls under the rubric of posttransplant T-cell lymphoproliferative disease, which is largely unrelated to Epstein-Barr virus infection. Anaplastic large-cell lymphoma (ALCL) is the most recognized form of posttransplant T-cell lymphoproliferative disease. Although the 6p25.3 translocation is seen in a variety of B-cell lymphoproliferative disorders, this particular translocation in the spectrum of T-cell lymphoproliferative disease is a fairly specific finding pointing toward a diagnosis of primary cutaneous ALCL and a rare subset of lymphomatoid papulosis. This translocation in the peripheral T-cell lymphoma setting serves as a favorable prognostic predictor. We report a case of an 81-year-old heart transplant recipient who developed an expansile neck mass 17 years after his heart transplant. A diagnosis of cutaneous ALCL was subsequently made with cytogenetic analysis yielding the 6p25.3 translocation. The characteristic biphasic morphology of a small-cell epidermotropic neoplastic cell populace in concert with a dermal based large-cell infiltrate characteristic for those cases of ALCL harboring this translocation was seen. After excision of the nodule, his azathioprine was withheld. He is currently alive and well without evidence of disease. PMID- 26863059 TI - Hidradenoma Papilliferum: A Clinicopathologic Study of 264 Tumors From 261 Patients, With Emphasis on Mammary-Type Alterations. AB - Hidradenoma papilliferum (HP), also known as papillary hidradenoma, is the most common benign lesion of the female anogenital area derived from anogenital mammary-like glands (AGMLG). HP can be viewed conceptually as the cutaneous counterpart of mammary intraductal papilloma. The authors have studied 264 cases of HP, detailing various changes in the tumor and adjacent AGMLG, with emphasis on mammary-type alterations. In many HP, the authors noticed changes typical for benign breast lesions, such as sclerosing adenosis-like changes, usual, and atypical ductal hyperplasia. Almost in a third of cases, remnants of AGMLG adjacent to the lesion were evident, manifesting columnar changes reminiscent of those seen in breast lesions. This study shows that the histopathological changes in HP run a broad spectrum comparable with that in the mammary counterpart and benign breast disease. PMID- 26863060 TI - Syringomatous Structures in Extramammary Paget Disease: A Potential Diagnostic Pitfall. AB - Primary extramammary Paget disease (EMPD) is a form of intraepithelial adenocarcinoma. Different morphological changes may accompany EMPD, including the presence of syringoma-like structures. The authors report 10 cases of EMPD, all of which manifested syringoma-like structures within the dermis both in areas involved by the carcinoma and beyond, including at the margins of the excisions. All patients were women, whose ages ranged from 49 to 93 years (median 75 years). The possible pathogenesis of the syringoma-like lesions is discussed. Awareness of these structures in vulvectomy specimens for EMPD is important to prevent misinterpretation of the syringoma-like lesions as an invasive component of the EMPD. PMID- 26863061 TI - Bilateral Aleukemic Myeloid Sarcoma of the Eyelids With Indolent Course. AB - Leukemic infiltrates may be seen in the skin in the absence of detectable bone marrow involvement. Leukemia cutis may exceptionally occupy the eyelids. An unusual case of a 58-year-old man presenting bilateral erythematous eyelid lesions, proven to be aleukemic leukemia cutis, is reported. Biopsy was conducted and hematoxylin/eosin stained sections were histologically evaluated. Immunohistochemistry was also performed.Light microscopy revealed cutaneous infiltration by a neoplastic population consisting of medium-sized cells. These cells infiltrated the overlying epidermis leading to focal microulcerations. The morphological and immunohistochemical characteristics of the neoplastic population were compatible with myeloid leukemia cutis. The bone marrow biopsy was normocellular for the patient's age. Although chemotherapy was advised, the patient refused any treatment. He remains free of leukemia or evolution of eyelid lesions approximately 1 year after diagnosis. Leukemia cutis of the eyelids is a rare manifestation of acute leukemia and may remain aleukemic in adults for an indefinite period of time. PMID- 26863062 TI - Congenital Blaschkoid Angiolymphoid Hyperplasia With Eosinophilia of the Anogenital Region. AB - Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic vascular disorder. It manifests as dermal or subcutaneous red to brown papules or nodules, most commonly on the head and neck; other less common sites include the trunk, extremities, genitalia, lips, and oral mucosa. Although ALHE is a benign disease, lesions are often persistent and difficult to eradicate. ALHE occurs more frequently in Asian young and middle-aged women. Histologically, it is characterized by a florid vascular proliferation with hobnail epithelioid endothelial cells surrounding by lymphocytic and eosinophilic infiltrate. Here, we reported congenital ALHE in a 2-year-old girl. Unilateral lesions had a blaschkoid segmental distribution in the anogenital region and were successfully treated with the Nd:YAG laser. PMID- 26863063 TI - Hybrid Epithelioid Schwannoma/Perineurioma. AB - We report a case of a 58-year-old who woman presented with a solitary slowly growing subcutaneous nodule covered by normally appearing skin on her left groin. Microscopically, the lesion was well circumscribed but unencapsulated, and showed biphasic cellular differentiation. One cell population was presented by small rounded (epithelioid) cells arranged singly, in small aggregates or short cords, whereas the second one was composed of cells with slender nuclei and delicate elongated bipolar cytoplasmic processes. On immunohistochemistry, the epithelioid component showed positive reaction for S-100 protein and negative for epithelial membrane antigen (EMA), thus compatible with schwannian differentiation and resembling epithelioid schwannoma. The other component showed a reverse immunophenotype being S-100 protein negative and EMA positive, thus corresponding to perineuriomatous differentiation. The clinicopathologic and immunohistochemical features of the lesion were compatible with hybrid epithelioid schwannoma/perineurioma, a rare morphological variant of peripheral nerve sheath tumors. PMID- 26863064 TI - Depth and Patterns of Adnexal Involvement in Primary Extramammary (Anogenital) Paget Disease: A Study of 178 Lesions From 146 Patients. AB - Extramammary Paget disease (EMPD) is a rare neoplasm usually presenting in the anogenital area, most commonly in the vulva. Adnexal involvement in primary EMPD is a very common feature and serves as a pathway for carcinoma to spread into deeper tissue. The depth of carcinomatous spread along the appendages and the patterns of adnexal involvement were studied in 178 lesions from 146 patients with primary EMPD. Hair follicles and eccrine ducts were the adnexa most commonly affected by carcinoma cells. The maximal depth of involvement was 3.6 mm in this series. When planning topical therapy or developing novel local treatment modalities for EMPD, this potential for significant deep spread along adnexa should be taken into account. PMID- 26863065 TI - Syringocystadenocarcinoma Papilliferum In Situ-Like Changes in Extramammary Paget Disease: A Report of 11 Cases. AB - The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface. PMID- 26863066 TI - Studying Microbial Communities In Vivo: A Model of Host-mediated Interaction Between Candida Albicans and Pseudomonas Aeruginosa in the Airways. AB - Studying host-pathogen interaction enables us to understand the underlying mechanisms of the pathogenicity during microbial infection. The prognosis of the host depends on the involvement of an adapted immune response against the pathogen. Immune response is complex and results from interaction of the pathogens and several immune or non-immune cellular types. In vitro studies cannot characterise these interactions and focus on cell-pathogen interactions. Moreover, in the airway, particularly in patients with suppurative chronic lung disease or in mechanically ventilated patients, polymicrobial communities are present and complicate host-pathogen interaction. Pseudomonas aeruginosa and Candida albicans are both problem pathogens, frequently isolated from tracheobronchial samples, and associated to severe infections, especially in intensive care unit. Microbial interactions have been reported between these pathogens in vitro but the clinical impact of these interactions remains unclear. To study the interactions between C. albicans and P. aeruginosa, a murine model of C. albicans airways colonization, followed by a P. aeruginosa-mediated acute lung infection was performed. PMID- 26863067 TI - Bladder Acellular Matrix Grafts Seeded with Adipose-Derived Stem Cells and Incubated Intraperitoneally Promote the Regeneration of Bladder Smooth Muscle and Nerve in a Rat Model of Bladder Augmentation. AB - The objective of this study was to investigate the feasibility of bladder acellular matrix grafts (BAMGs) seeded with adipose-derived stem cells (ASCs) followed by intraperitoneal incubation for bladder reconstruction in a rat model of bladder augmentation, and to explore the underlying mechanism. Autologous CM DiI-labeled ASC-seeded (experimental group) and unseeded (control group) BAMGs were incubated in the peritoneum of male rats for 2 weeks and then harvested for bladder augmentation. Histological analysis of the incubated BAMGs revealed numerous cells growing in homogeneous collagen bundles in both groups. In the control BAMGs, these cells were mesenchyme derived, while in the ASC-seeded BAMGs, myofibroblasts and mesothelial cells were found inside and on the surface of the scaffold, respectively. Immunofluorescence analysis demonstrated that some of the myofibroblasts were transdifferentiated from the ASCs after 2 weeks of intraperitoneal incubation. The greater bladder capacity was found in the experimental group than the control group both 4 and 14 weeks postoperatively. Histological analysis revealed that the entire urothelium regenerated well both in the experimental group and the control group without significant difference 4 weeks and 14 weeks postoperatively. From the quantitative data of immunohistochemical and immunofluorescence staining, the smooth muscle cells (SMCs) regenerated significantly better in the experimental group than the control group both 4 weeks and 14 weeks postoperatively. Also significantly more nerve cells were found in the experimental group 14 weeks postoperatively. At 4 weeks postoperatively, the immunofluorescence double staining revealed that some SMCs in the BAMG were transdifferentiated from the implanted ASCs, but no CM-DiI labeling of ASCs was detected 14 weeks postoperatively. Taken together, our results demonstrate that ASC-seeded and peritoneally incubated BAMGs promote not only the morphological regeneration of the bladder smooth muscle and nerve, but also the bladder capacity, which indicates their potential for bladder regeneration. PMID- 26863068 TI - Positive Association Between Betatrophin and Diabetic Retinopathy Risk in Type 2 Diabetes Patients. AB - Betatrophin is a recently identified protein that has been shown to be associated with lipid metabolism and insulin resistance. This study aimed to measure serum betatrophin concentrations in patients with type 2 diabetes (T2DM) and evaluate the association of betatrophin with diabetic retinopthy (DR). Serum betatrophin concentrations were compared between (1) gender-, age- and body mass index matched T2DM patients with (n=17) or without (n=33) DR; (2) gender-, age-, and body mass index-matched healthy subjects (n=31), newly-diagnosed T2DM patients before treatment (n=24), and T2DM patients under antidiabetic treatment (n=35). Serum betatrophin concentrations were determined by the enzyme-linked immunosorbent assay. Multivariate logistic regression was performed to assess the association between betatrophin concentration and DR. Serum betatrophin concentration was significantly associated with DR in T2DM patients under treatment (Odds Ratio 2.01; 95% Confidence Interval 1.12-3.60; p=0.019). Betatrophin concentrations were significantly increased in treated T2DM patients compared to the healthy subjects (4.17+/-0.60 vs. 0.54+/-0.07 ng/ml; p<0.001). Serum betatrophin concentrations are increased in T2DM patients under antidiabetic treatment and positively associated with diabetic retinopathy. PMID- 26863069 TI - Theoretical study of adsorption of amino acids on graphene and BN sheet in gas and aqueous phase with empirical DFT dispersion correction. AB - Understanding interactions of biomolecules with nanomaterials at the molecular level is crucial to design new materials for practical use. In the present study, adsorption of three distinct types of amino acids, namely, valine, arginine and aspartic acid, over the surface of structurally analogous but chemically different graphene and BN nanosheets has been explored within the formalism of DFT. The explicit dispersion correction incorporated in the computational methodology improves the accuracy of the results by accounting for long range van der Waals interactions and is essential for agreement with experimental values. The real biological environment has been mimicked by re-optimizing all the model structures in an aqueous medium. The study provides ample evidence in terms of adsorption energy, solvation energy, separation distance and charge analysis to conclude that both the nano-surfaces adsorb the amino acids with release of energy and there are no bonded interactions between the two. The polarity of the BN nanosheet provides it an edge over the graphene surface to have more affinity towards amino acids. PMID- 26863070 TI - Trapped ion chain thermometry and mass spectrometry through imaging. AB - We demonstrate a spatial-imaging thermometry technique for ions in a one dimensional Coulomb crystal by relating their imaged spatial extent along the linear radiofrequency ion trap axis to normal modes of vibration of coupled oscillators in a harmonic potential. We also use the thermal spatial spread of "bright" ions in the case of a two-species mixed chain to measure the center-of mass resonance frequency of the entire chain and infer the molecular composition of the co-trapped "dark" ions. These non-destructive techniques create new possibilities for better understanding of sympathetic cooling in mixed-ion chains, improving few-ion mass spectrometry, and trapped-ion thermometry without requiring a scan of Doppler cooling parameters. PMID- 26863071 TI - Direct matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of lysozyme contained in hen egg white. AB - As a natural antibacterial peptide, lysozyme (LZ) is widely used in medicine and the food industry. Despite many years of research on this compound, its new antibacterial properties are still to be determined. The primary aim of this work is to demonstrate the application of the matrix-assisted laser desorption ionization (MALDI) time-of-flight mass spectrometric analysis of LZ directly in hen egg white samples without extraction thereof. The egg white samples were kept over 10 weeks at room temperature and measured every week. The resulting positive and negative ion mass spectra were then compared to determine the intensity of the LZ mass peak. Storage of the egg white for over 10 weeks did not influence the LZ mass peak intensity (both positive and negative). It can be concluded that the LZ concentration in the egg white samples did not vary with time. The effect of the matrix/sample ratio on LZ detection was also examined, and it was found to be different in the case of positive and negative ionization. The mass peaks of LZ oligomeric forms were observed in all mass spectra, so the MALDI method could be used in subsequent studies. PMID- 26863072 TI - Identification and quantification of unknown antioxidants in plastic materials by ultrasonic extraction and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. AB - Mass spectrometry has been applied to the targeted analysis of commonly used additives (such as Irganox 1010, Irganox 1076, Irgafos 168, etc.) in plastic materials, but a fast and straightforward method for the non-targeted identification and quantification of unusual or potentially new antioxidant additives is still unavailable. In this study, a novel and simple method for the identification and quantification of unknown antioxidant additives in plastic food packaging using ultrasonic extraction and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry has been developed. A method for the Irganox series analyzed here has not been reported previously. Unknown antioxidant additives have been identified by accurate m/z determination, MS(2) fragments and comparison with synthesized standards. The mass fragmentation patterns and structural assignments of these antioxidants have been studied. Parameters affecting the efficiency of the process, such as extraction solvents, extraction volume, extraction time and chromatographic conditions, have been studied and optimized. Ultrasonic extraction of plastic materials (40 mg) with dichloromethane (0.5 mL) at 25 degrees C was applied as optimal. Limits of detection of the target additives ranged from 0.5 ng g(-1) to 1.5 ng g(-1), and the detection was linear over the range studied (0.01-1.5 ug mg(-1), r(2)>0.99). The accuracy of the method has been tested by relative recovery experiments with spiked samples, with results ranging from 94.3% to 104.8%, and the precision (relative standard deviation) was within 11.0% (n=3). Finally, the method has been successfully applied to the determination of antioxidants in several real plastic samples. PMID- 26863073 TI - Synthesis and characterization of anaerobic degradation biomarkers of n-alkanes via hydroxylation/carboxylation pathways. AB - Metabolite profiling is a powerful method in research on anaerobic biodegradation of hydrocarbons. Hydroxylation and carboxylation are proposed pathways in anaerobic degradation but very little direct evidence is available about metabolites and signature biomarkers. 2-Acetylalkanoic acid is a potential signature metabolite because of its unique and specific structure among possible intermediates. A procedure for the synthesis of four homologues with various carbon chain lengths was proposed and the characteristics of 2-acetyl- alkanoic acid esters were investigated using four derivatization processes, namely methyl, ethyl, n-butyl and trimethylsilyl esterification. Four intermediate fragments observed were at m/z 73 + 14n, 87 + 14n, 102 + 14n (n = 1, 2 and 4 for methyl, ethyl and n-butyl ester, respectively) and [M - 42]+ for three of the derivatization methods. For silylation, characteristic ions were observed at m/z 73, 117, [M - 42](+) and [M - 55](+). These are basic and significant data for the future identification of potential intermediates of the hydroxylation and carboxylation pathways in hydrocarbon degradation. PMID- 26863074 TI - Letter: Supermetallization of peptides and proteins with tetravalent metal Th(IV). AB - Supermetallization is the recently observed phenomenon of the formation of complex ions of peptide-metal in the gas phase when the peptide accepts an unexpectedly large number of metal atoms. It has been found that supermetallization takes place during electrospray ionization when charged droplets are evaporating at relatively high temperature (ca 400 degrees C). In the present paper, we demonstrate supermetallized complexes of small protein ubiquitin and two peptides with Th(IV). We have observed complexes of ubiquitin with up to five thorium atoms, and attaching each Th(IV) requires the removal of four hydrogen atoms. To our knowledge, this is the first demonstration of gas phase complexes of peptides and proteins with tetravalent metal atoms.. PMID- 26863075 TI - Letter: High-mass capabilities of positive-ion and negative-ion direct analysis in real time mass spectrometry. AB - Of the ionic liquid 1-butyl-3-methylimidazolium (C(+)) tricyanomethide (A(-)) high-mass cluster ions of both positive ([C(n)A(n-1)](+)) and negative ([C(n 1)A(n)](-)) charge were generated and detected by direct analysis in real time (DART) Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS). After optimization of the settings of the DART ionization source and of the mass analyzer ions of m/z values unprecedented in DART-MS were detected. Thus, the upper m/z limits of positive-ion and negative-ion DART- MS were substantially expanded. Negative-ion DART-MS delivered cluster ions up to [C(15)A(16)](-), m/z 3527 (nominal mass of monoisotopic ion), while positive-ion DART-MS even yielded ions up to [C(30)A(29)](+), m/z 6784. The identification of the cluster ions is supported by their accurate mass and exact mass differences corresponding to CA between adjacent cluster ion peaks. PMID- 26863077 TI - Cross-cultural adaptation of the German version of the Quality of Life in Alzheimer's Disease scale - Nursing Home version (QoL-AD NH). AB - Dementia is a chronic and currently incurable syndrome. Therefore, quality of life (QoL) is a major goal when caring for people with dementia (Gibson et al., 2010) and a major outcome in dementia research (Moniz-Cook et al., 2008). The measurement of QoL, especially proxy-rating, is challenging because of the proxy perspective (Pickard and Knight, 2005), reliability (Dichter et al., 2016), validity (O'Rourke et al., 2015), and responsiveness (Perales et al., 2013). Probably due to these challenges, it has not been possible to show positive effects for QoL in almost all non-pharmacological interventions for people with dementia (Cooper et al., 2012). One recommended (Moniz-Cook et al., 2008) and frequently used instrument is the Quality of Life in Alzheimer's Disease scale (QoL-AD), which was originally developed in the US for community-dwelling people with dementia. The QoL-AD consists of 13 items based on a 4-point Likert scale ranging from "1"=poor to "4"=excellent (Logsdon et al., 1999). The original instrument has been adapted for people living in nursing homes (NH) by Edelmann et al. (2005). PMID- 26863078 TI - Role of electrostatic interactions in the adsorption kinetics of nanoparticles at fluid-fluid interfaces. AB - The adsorption of particles to the fluid-fluid interface is a key factor for the stabilization of fluid-fluid interfaces such as those found in emulsions, foams and bijels. However, for the formation of stable particle-laden interfaces, the particles must migrate to the interface from the bulk. Recent studies show that the adsorption of particles to the interface formed during emulsification is influenced by the surface charge of the particles. To further investigate this phenomenon, we study the effect of the surface charge of the particle on the adsorption kinetics of particles to the oil-water interface. By suspending a drop of aqueous dispersion of charge stabilized nanoparticles in decane, the adsorption dynamics of particles to the decane-water interface is studied using the dynamic surface tension measurements. When the particles are highly charged (low salt), a negligible change in the interface tension is observed indicating that almost no particles are adsorbed. These results show that the charged particles experience an energy barrier when they approach the interface. But when the particle surface charge is screened by the addition of monovalent salt, a significant reduction in surface tension is observed indicating the migration and adsorption of particles to the decane-water interface. We estimate the effective diffusivity of particles to the interface by analyzing the initial decay in the measured surface tension by considering particle laden drops containing different amounts of salt using the modified Ward and Tordai theory. This effective diffusivity is used to calculate the energy barrier for the adsorption of particles to the interface. The energy barrier from the analysis of dynamic surface tension data agrees well with the concept of image charge repulsion which inhibits the adsorption of highly charged particles to the interface. By considering various types of relevant interactions, we derive an analytical expression that qualitatively captures the effect of the surface charge on the equilibrium surface coverage of particles at the drop surface. PMID- 26863079 TI - Dynamical regimes of four almost identical chemical oscillators coupled via pulse inhibitory coupling with time delay. AB - The dynamic regimes in networks of four almost identical spike oscillators with pulsatile coupling via inhibitor are systematically studied. We used two models to describe individual oscillators: a phase-oscillator model and a model for the Belousov-Zhabotinsky reaction. A time delay tau between a spike in one oscillator and the spike-induced inhibitory perturbation of other oscillators is introduced. Diagrams of all rhythms found for three different types of connectivities (unidirectional on a ring, mutual on a ring, and all-to-all) are built in the plane C(inh)-tau, where C(inh) is the coupling strength. It is shown analytically and numerically that only four regular rhythms are stable for unidirectional coupling: walk (phase shift between spikes of neighbouring oscillators equals the quarter of the global period T), walk-reverse (the same as walk but consecutive spikes take place in the direction opposite to the direction of connectivity), anti-phase (any two neighbouring oscillators are anti-phase), and in-phase oscillations. In the case of mutual on the ring coupling, an additional in-phase anti-phase mode emerges. For all-to-all coupling, two new asymmetrical patterns (two-cluster and three-cluster modes) have been found. More complex rhythms are observed at large C(inh), when some oscillators are suppressed completely or generate smaller number of spikes than others. PMID- 26863080 TI - The crucial role of water in shaping low-barrier hydrogen bonds. AB - Low-barrier hydrogen bonds (LBHBs) are key components in a range of chemical processes, often appearing in metal-mediated catalytic applications. The formation of LBHBs has generally been attributed to the particular geometric arrangement of the surrounding atoms and molecules, yet few specific atomic-level details have emerged. In this study, several metal maleate tetrahydrates have been studied using a combination of solid-state density functional theory, terahertz spectroscopy, and X-ray diffraction to evaluate the significance of both water molecules and metal cations in guiding LBHB formation and function. The findings reveal the assumption that metal identity is of paramount importance to be incomplete, and that the metal cation does not directly influence the LBHB in the maleate ligand. Rather, the characteristics are regulated by water molecule positioning, asserting the critical role of water in governing LBHBs and providing new insight into their formation mechanisms. PMID- 26863081 TI - A Basic Positron Emission Tomography System Constructed to Locate a Radioactive Source in a Bi-dimensional Space. AB - A simple Positron Emission Tomography (PET) prototype has been constructed to fully characterize its basic working principles. The PET prototype was created by coupling plastic scintillator crystals to photomultipliers or PMT's which are placed at opposing positions to detect two gamma rays emitted from a radioactive source, of which is placed in the geometric center of the PET set-up. The prototype consists of four detectors placed geometrically in a 20 cm diameter circle, and a radioactive source in the center. By moving the radioactive source centimeters from the center the system one is able to detect the displacement by measuring the time of flight difference between any two PMT's and, with this information, the system can calculate the virtual position in a graphical interface. In this way, the prototype reproduces the main principles of a PET system. It is capable to determine the real position of the source with intervals of 4 cm in 2 lines of detection taking less than 2 min. PMID- 26863082 TI - A device for co-culturing autonomic neurons and cardiomyocytes using micro fabrication techniques. AB - It is still unclear how the activity of sympathetic and parasympathetic neurons influences the activity of cardiomyocytes in culture. We developed a device for co-culturing sympathetic neurons, parasympathetic neurons, and cardiomyocytes using micro-fabrication techniques. Morphological connections between each type of autonomic neuron and the cardiomyocytes were observed by immunostaining. The inter-beat-interval (IBI) of the cardiomyocytes was modulated after electrically stimulating each type of autonomic neuron. Modulation of the IBI was blocked by the addition of pharmacological blockers to the culture medium. These results suggest that the co-culture device can be utilized to understand how the activity of sympathetic neurons and parasympathetic neurons influences the activity of cardiomyocytes in the culture environment. PMID- 26863083 TI - Dysiherbols A-C and Dysideanone E, Cytotoxic and NF-kappaB Inhibitory Tetracyclic Meroterpenes from a Dysidea sp. Marine Sponge. AB - Four new tetracyclic meroterpnes, dysiherbols A-C (1-3) and dysideanone E (4), were isolated from a Dysidea sp. marine sponge collected from the South China Sea. Their complete structures and absolute configurations were unambiguously determined by a combination of NMR spectroscopic data, ECD calculations, and single-crystal X-ray diffraction analysis. Within the sesquiterpene quinol structures, dysiherbols A-C possess an intriguing 6/6/5/6-fused tetracyclic carbon skeleton. The NF-kappaB inhibitory and cytotoxic activity evaluation disclosed that dysiherbol A (1) showed potent activity with respective IC50 values of 0.49 and 0.58 MUM, which were about 10-fold and 20-fold more potent than those of dysiherbols B (2) and C (3), which feature hydroxy and ketone carbonyl groups at the C-3 position. PMID- 26863087 TI - Cloning and Large-Scale Production of High-Capacity Adenoviral Vectors Based on the Human Adenovirus Type 5. AB - High-capacity adenoviral vectors (HCAdV) devoid of all viral coding sequences represent one of the most advanced gene delivery vectors due to their high packaging capacity (up to 35 kb), low immunogenicity and low toxicity. However, for many laboratories the use of HCAdV is hampered by the complicated procedure for vector genome construction and virus production. Here, a detailed protocol for efficient cloning and production of HCAdV based on the plasmid pAdFTC containing the HCAdV genome is described. The construction of HCAdV genomes is based on a cloning vector system utilizing homing endonucleases (I-CeuI and PI SceI). Any gene of interest of up to 14 kb can be subcloned into the shuttle vector pHM5, which contains a multiple cloning site flanked by I-CeuI and PI SceI. After I-CeuI and PI-SceI-mediated release of the transgene from the shuttle vector the transgene can be inserted into the HCAdV cloning vector pAdFTC. Because of the large size of the pAdFTC plasmid and the long recognition sites of the used enzymes associated with strong DNA binding, careful handling of the cloning fragments is needed. For virus production, the HCAdV genome is released by NotI digest and transfected into a HEK293 based producer cell line stably expressing Cre recombinase. To provide all adenoviral genes for adenovirus amplification, co-infection with a helper virus containing a packing signal flanked by loxP sites is required. Pre-amplification of the vector is performed in producer cells grown on surfaces and large-scale amplification of the vector is conducted in spinner flasks with producer cells grown in suspension. For virus purification, two ultracentrifugation steps based on cesium chloride gradients are performed followed by dialysis. Here tips, tricks and shortcuts developed over the past years working with this HCAdV vector system are presented. PMID- 26863088 TI - Interplay between Two Allosteric Sites and Their Influence on Agonist Binding in Human MU Opioid Receptor. AB - Allostery is a widespread mechanism that allows for precise protein tuning. Its underlying mechanisms are elusive, particularly when there are multiple allosteric sites at the protein. This concerns also G-protein-coupled receptors (GPCRs), which are targets for a vast part of currently used drugs. To address this issue, we performed molecular dynamics simulations of a GPCR-human MU opioid receptor (MOR) in a native-like environment, with full agonist (R)-methadone, Na(+) ions, and a positive modulator BMS986122 in various configurations. We found that MOR's seventh transmembrane helix (TM VII) is central for allosteric signal transmission, and modulators affect its bending and rotation. The PAM stabilizes favorable agonist interactions, while Na(+) tends to disrupt agonist binding. We identified two residues involved in allosteric signal transmission: Trp 7.35 at the top and Tyr 7.53 at the bottom of TM VII. PMID- 26863089 TI - Core-Shell Coating Silicon Anode Interfaces with Coordination Complex for Stable Lithium-Ion Batteries. AB - In situ core-shell coating was used to improve the electrochemical performance of Si-based anodes with polypyrrole-Fe coordination complex. The vast functional groups in the organometallic coordination complex easily formed hydrogen bonds when in situ modifying commercial Si nanoparticles. The incorporation of polypyrrole-Fe resulted in the conformal conductive coating surrounding each Si nanoparticle, not only providing good electrical connection to the particles but also promoting the formation of a stable solid-electrolyte-interface layer on the Si electrode surface, enhancing the cycling properties. As an anode material for Li-ion batteries, modified silicon powders exhibited high reversible capacity (3567 mAh/g at 0.3 A/g), good rate property (549.12 mAh/g at 12 A/g), and excellent cycling performance (reversible capacity of 1500 mAh/g after 800 cycles at 1.2 A/g). The constructed novel concept of core-shell coating Si particles presented a promising route for facile and large-scale production of Si-based anodes for extremely durable Li-ion batteries, which provided a wide range of applications in the field of energy storage of the renewable energy derived from the solar energy, hydropower, tidal energy, and geothermal heat. PMID- 26863090 TI - Global analysis of publicly available safety data for 9,801 substances registered under REACH from 2008-2014. AB - The European Chemicals Agency (ECHA) warehouses the largest public dataset of in vivo and in vitro toxicity tests. In December 2014 this data was converted into a structured, machine readable and searchable database using linguistic search engines. It contains data for 9,801 unique substances, 3,609 unique study descriptions and 816,048 study documents.This allows exploring toxicological data on a scale far larger than previously available. Substance similarity analysis was used to determine clustering of substances for hazards by mapping to PubChem. Similarity was measured using PubChem 2D conformational substructure fingerprints, which were compared via the Tanimoto metric. Following K-Core filtration, the Blondel et al.(2008) module recognition algorithm was used to identify chemical modules showing clusters of substances in use within the chemical universe. Global Harmonized System of Classification and Labelling provides a valuable information source for hazard analysis. The most prevalent hazards are H317 "May cause an allergic skin reaction" with 20% and H318 "Causes serious eye damage" with 17% positive substances. Such prevalences obtained for all hazards here are key for the design of integrated testing strategies. The data allowed estimation of animal use. ECHA cover about 20% of substances in the high-throughput biological assay database Tox21 (1,737 substances) and have a 917 substance overlap with the Comparative Toxicogenomics Database (~7% of CTD). The biological data available in these datasets combined with ECHA in vivo endpoints have enormous modeling potential. A case is made that REACH should systematically open regulatory data for research purposes. PMID- 26863091 TI - Does naming accuracy improve through self-monitoring of errors? AB - This study examined spontaneous self-monitoring of picture naming in people with aphasia. Of primary interest was whether spontaneous detection or repair of an error constitutes an error signal or other feedback that tunes the production system to the desired outcome. In other words, do acts of monitoring cause adaptive change in the language system? A second possibility, not incompatible with the first, is that monitoring is indicative of an item's representational strength, and strength is a causal factor in language change. Twelve PWA performed a 615-item naming test twice, in separate sessions, without extrinsic feedback. At each timepoint, we scored the first complete response for accuracy and error type and the remainder of the trial for verbalizations consistent with detection (e.g., "no, not that") and successful repair (i.e., correction). Data analysis centered on: (a) how often an item that was misnamed at one timepoint changed to correct at the other timepoint, as a function of monitoring; and (b) how monitoring impacted change scores in the Forward (Time 1 to Time 2) compared to Backward (Time 2 to Time 1) direction. The Strength hypothesis predicts significant effects of monitoring in both directions. The Learning hypothesis predicts greater effects in the Forward direction. These predictions were evaluated for three types of errors--Semantic errors, Phonological errors, and Fragments--using mixed-effects regression modeling with crossed random effects. Support for the Strength hypothesis was found for all three error types. Support for the Learning hypothesis was found for Semantic errors. All effects were due to error repair, not error detection. We discuss the theoretical and clinical implications of these novel findings. PMID- 26863092 TI - Diastereoselective Synthesis and Conformational Analysis of (2R)- and (2S) Fluorostatines: An Approach Based on Organocatalytic Fluorination of a Chiral Aldehyde. AB - Stereoselectively fluorinated analogues of the amino acid statine have been efficiently synthesized. The key step is an organocatalytic electrophilic fluorination of a chiral beta-oxygenated aldehyde, which provided a test of both diastereoselectivity and chemoselectivity. The target statine analogues were found to adopt unique conformations influenced by the fluorine gauche effect, rendering them potentially valuable building blocks for incorporation into bioactive peptides. PMID- 26863093 TI - Electron Paramagnetic Resonance Spectroscopic Study on Nonequilibrium Reaction Pathways in the Photolysis of Solid Nitromethane (CH3NO2) and D3-Nitromethane (CD3NO2). AB - Thin films of nitromethane (CH3NO2) along with its isotopically labeled counterpart D3-nitromethane (CD3NO2) were photolyzed at discrete wavelength between 266 nm (4.7 eV) and 121 nm (10.2 eV) to explore the underlying mechanisms involved in the decomposition of model compounds of energetic materials in the condensed phase at 5 K. The chemical modifications of the ices were traced in situ via electron paramagnetic resonance, thus focusing on the detection of (hitherto elusive) reaction intermediates and products with unpaired electrons. These studies revealed the formation of two carbon-centered radicals [methyl (CH3), nitromethyl (CH2NO2)], one oxygen-centered radical [methoxy (CH3O)], two nitrogen-centered radicals [nitrogen monoxide (NO), nitrogen dioxide (NO2)], as well as atomic hydrogen (H). The decomposition products of these channels and the carbon-centered nitromethyl (CH2NO2) radical in particular represent crucial reaction intermediates leading via sequential molecular mass growth processes in the exposed nitromethane samples to complex organic molecules as predicted previously by dynamics calculations. The detection of the nitromethyl (CH2NO2) radical along with atomic hydrogen (H) demonstrated the existence of a high energy decomposition pathway, which is closed under collisionless conditions in the gas phase. PMID- 26863094 TI - Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation. AB - Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses. PMID- 26863095 TI - Gas-Phase Cytosine and Cytosine-N1-Derivatives Have 0.1-1 ns Lifetimes Near the S1 State Minimum. AB - Ultraviolet radiative damage to DNA is inefficient because of the ultrafast S1 ? S0 internal conversion of its nucleobases. Using picosecond pump-ionization delay measurements, we find that the S1((1)pipi*) state vibrationless lifetime of gas phase keto-amino cytosine (Cyt) is tau = 730 ps or ~ 700 times longer than that measured by femtosecond pump-probe ionization at higher vibrational excess energy, Eexc. N1-Alkylation increases the S1 lifetime up to tau = 1030 ps for N1 ethyl-Cyt but decreases it to 100 ps for N1-isopropyl-Cyt. Increasing the vibrational energy to Eexc = 300-550 cm(-1) decreases the lifetimes to 20-30 ps. The nonradiative dynamics of S1 cytosine is not solely a property of the amino pyrimidinone chromophore but is strongly influenced by the N1-substituent. Correlated excited-state calculations predict that the gap between the S2((1)nOpi*) and S1((1)pipi*) states decreases along the series of N1 derivatives, thereby influencing the S1 state lifetime. PMID- 26863096 TI - Local Lattice Distortions in Mn[N(CN)2]2 under Pressure. AB - We combined synchrotron-based infrared spectroscopy, Raman scattering, and diamond anvil cell techniques with complementary lattice dynamics calculations to reveal local lattice distortions in Mn[N(CN)2]2 under compression. Strikingly, we found a series of transitions involving octahedral counter-rotations, changes in the local Mn environment, and deformations of the superexchange pathway. In addition to reinforcing magnetic property trends, these pressure-induced local lattice distortions may provide an avenue for the development of new functionalities. PMID- 26863097 TI - Career Advice for Graduate Students and Postdoctoral Fellows. PMID- 26863098 TI - Laparoscopic Low Anterior Resection of the Rectum with Transanal Prolapsing Specimen Extraction: Early Experience with 23 Patients. AB - OBJECTIVE: For laparoscopic low anterior resection of the rectum, a small additional incision is needed to extract the specimen. We describe an adjustment technique, which inserted the anvil and extracted the specimen through transanal pathway. METHODS: Between July 2010 and July 2012, 23 patients underwent laparoscopic rectal surgery with transanal anvil insertion and transanal prolapsing specimen extraction. All perioperative data and short-term outcomes were recorded in a database. RESULTS: The mean patient age was 61.3 years (range 47-68 years). Of the 23 patients, 17 underwent resection for rectal carcinoma and 6 had tubulovillous adenomas. No intraoperative complications occurred. The mean operative time was 137 minutes (range 118-170 minutes). The distal margins, circumferential resection margins, and lymph node dissections were oncologically adequate for all malignancies. One patient experienced anastomotic leakage (4.3%), treated conservatively. One male patient with benign prostatic hyperplasia suffered from postoperative urinary retention. The average postoperative hospital stay was 11.3 days (range 7-21 days). No patients experienced anal dysfunction. At a median follow-up of 26 months, there were no tumor recurrences. CONCLUSION: The technique of transanal prolapsing specimen extraction for laparoscopic low anterior resection of the rectum is feasible and safe for selected patients. PMID- 26863099 TI - Lewis Acid Catalyzed Regioselective Hydroheteroarylation of Pentafulvenes. AB - A diverse approach toward the catalytic regioselective nucleophilic addition of nitrogen heterocycles to Lewis acid activated pentafulvenes has been established. The developed protocol introduces pentafulvenes as nonsymmetrical alkenes for the hydroheteroarylation reaction, providing alkylidenecyclopentenylation at the C-3 position of indoles and the C-2 position of pyrrole. PMID- 26863100 TI - Techniques for nonlinear optical characterization of materials: a review. AB - Various techniques to characterize the nonlinear (NL) optical response of centro symmetric materials are presented and evaluated with emphasis on the relationship between the macroscopic measurable quantities and the microscopic properties of photonic materials. NL refraction and NL absorption of the materials are the phenomena of major interest. The dependence of the NL refraction and NL absorption coefficients on the nature of the materials was studied as well as on the laser excitation characteristics of wavelength, intensity, spatial profile, pulse duration and pulses repetition rate. Selected experimental results are discussed and illustrated. The various techniques currently available were compared and their relative advantages and drawbacks were evaluated. Critical comparisons among established techniques provided elements to evaluate their accuracies and sensitivities with respect to novel methods that present improvements with respect to the conventional techniques. PMID- 26863101 TI - Pulmonary and Critical Care In-Service Training Examination Score as a Predictor of Board Certification Examination Performance. AB - RATIONALE: Most trainees in combined pulmonary and critical care medicine fellowship programs complete in-service training examinations (ITEs) that test knowledge in both disciplines. Whether ITE scores predict performance on the American Board of Internal Medicine Pulmonary Disease Certification Examination and Critical Care Medicine Certification Examination is unknown. OBJECTIVES: To determine whether pulmonary and critical care medicine ITE scores predict performance on subspecialty board certification examinations independently of trainee demographics, program director competency ratings, fellowship program characteristics, and prior medical knowledge assessments. METHODS: First- and second-year fellows who were enrolled in the study between 2008 and 2012 completed a questionnaire encompassing demographics and fellowship training characteristics. These data and ITE scores were matched to fellows' subsequent scores on subspecialty certification examinations, program director ratings, and previous scores on their American Board of Internal Medicine Internal Medicine Certification Examination. Multiple linear regression and logistic regression were used to identify independent predictors of subspecialty certification examination scores and likelihood of passing the examinations, respectively. MEASUREMENTS AND MAIN RESULTS: Of eligible fellows, 82.4% enrolled in the study. The ITE score for second-year fellows was matched to their certification examination scores, which yielded 1,484 physicians for pulmonary disease and 1,331 for critical care medicine. Second-year fellows' ITE scores (beta = 0.24, P < 0.001) and Internal Medicine Certification Examination scores (beta = 0.49, P < 0.001) were the strongest predictors of Pulmonary Disease Certification Examination scores, and were the only significant predictors of passing the examination (ITE odds ratio, 1.12 [95% confidence interval, 1.07-1.16]; Internal Medicine Certification Examination odds ratio, 1.01 [95% confidence interval, 1.01-1.02]). Similar results were obtained for predicting Critical Care Medicine Certification Examination scores and for passing the examination. The predictive value of ITE scores among first-year fellows on the subspecialty certification examinations was comparable to second-year fellows' ITE scores. CONCLUSIONS: The Pulmonary and Critical Care Medicine ITE score is an independent, and stronger, predictor of subspecialty certification examination performance than fellow demographics, program director competency ratings, and fellowship characteristics. These findings support the use of the ITE to identify the learning needs of fellows as they work toward subspecialty board certification. PMID- 26863102 TI - The Italian multiregional thalassemia registry: Centers characteristics, services, and patients' population. AB - OBJECTIVES: The prognosis of beta-Thalassemia major and other congenital hemoglobinopathies has profoundly changed over the last decades. Moreover, only few countries in Europe provide dedicated services and the description of the measures for patients monitoring and treatment is overall very scarce. The HTA Thal project is aimed to identify the services available in Italy and to collect epidemiological and clinical data on the thalassemic population (HTA-Thal Registry). METHODS: A map of the existing centers was created and two electronic questionnaires were completed with information on the services and patients. RESULTS: On 182 centers identified, 60 completed the two questionnaires. Centers resulted to be extremely heterogeneous in terms of size, age of patients in care, and services availability. The transition of pediatric patients to adult centers was not guaranteed. Thousand eight hundred and seventy-three beta-Thalassemia major patients (of which 259 pediatrics), regularly transfused, were registered. Deferasirox is the most used chelator as monotherapy (616 patients) and its use prevails in younger patients. A higher number of patients (847 patients) use Deferoxamine, either alone (448 patients) or in combination with DFP (399 patients), while 782 patients use Deferiprone alone (383 patients) or in combination (399 patients). 31.6 and 66.6% of centers were not equipped for specialized visits or local MRI, respectively. Centers with 30-80 patients show the high percentage of patients appropriately monitored when compared to smaller or bigger centers. CONCLUSIONS: This analysis confirms the importance of patients' registries for the collection of large datasets and the need for dedicated 'specialized centers' equipped to provide the best standard treatment to patients. PMID- 26863103 TI - Bile Acid Metabolome after an Oral Lipid Tolerance Test by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). AB - CONTEXT: Besides their role in intestinal resorption of lipids, bile acids are regarded as endocrine and metabolic signaling molecules. The detailed profile of bile acid species in peripheral blood after an oral lipid tolerance test (OLTT) is unknown. OBJECTIVE: We quantified the regulation of 18 bile acids after OLTT in healthy individuals. MATERIAL AND METHODS: 100 volunteers were characterized by anthropometric and laboratory parameters and underwent OLTT. Venous blood was drawn in the fasted state (0 h) and at 2h, 4h, and 6 h after OLTT. Serum concentrations of 18 bile acids were measured by LC-MS/MS. RESULTS: All of the 6 taurine-conjugated bile acids (TUDCA, THDCA, TCA, TCDCA, TDCA, TLCA) and all of the 6 glycine-conjugated bile acids (GUDCA, GHDCA, GCA, GCDCA, GDCA, GLCA) rose significantly at 2h and remained elevated during OLTT. Of the primary bile acids, CA remained unchanged, whereas CDCA significantly decreased at 4h. Of the secondary bile acids, DCA, UDCA and HDCA were not altered, whereas LCA decreased. There was a significant positive correlation between the intestinal feed-back regulator of bile acid synthesis FGF-19 and bile acids. This correlation seems to depend on all of the six taurine-conjugated bile acids and on GCA, GDCA, and GCDCA. Females and users of hormonal contraception displayed higher levels of taurine-conjugated bile acids. CONCLUSIONS: The novelty of the study is based on the identification of single bile acids during OLTT. LC-MS/MS-based quantification of bile acids in serum provides a reliable tool for future investigation of endocrine and metabolic effects of bile acids. PMID- 26863104 TI - What constitutes the M1 segment of the middle cerebral artery? AB - Intravenous tissue plasminogen activator has limited efficacy in fibrinolysis of large proximal intracranial thrombi. Thus, recent endovascular acute stroke trials restricted their selection criteria to patients with proximal occlusions in the anterior circulation. Although the terminal internal carotid artery occlusion is relatively easy to identify, there is often a debate as to what constitutes a proximal (involving the M1 segment) versus a distal (involving the M2 segment and beyond) middle cerebral artery occlusion. In light of overwhelming evidence demonstrating superiority of endovascular treatment in patients with proximal occlusion, this distinction has significant practical implications in patient selection. Here we present a brief review of the proximal (M1) segment of the middle cerebral artery anatomy and provide practical methods to recognize and separate the M1 and M2 segments. In keeping with the belief that CT angiography (CTA) (preferably multiphase CTA) is the ideal screening test for patients with emergent large vessel occlusion, we have provided tips for expeditious and accurate vascular imaging interpretation. PMID- 26863105 TI - Assessment of intracranial aneurysm rupture based on morphology parameters and anatomical locations. AB - OBJECTIVES: The aim of the present study was to identify image-based morphological parameters and anatomical locations associated with intracranial aneurysm (IA) rupture. METHODS: Nine morphological parameters and aneurysm location were evaluated in 150 patients with saccular IAs (82 unruptured, 68 ruptured) using three-dimensional geometry. Aneurysm location and morphological parameters including size, aspect ratio, size ratio, height-width ratio, flow angle, aneurysm inclination angle, parent artery angle, vessel angle, and aneurysm shape were explored to identify a correlation with aneurysm rupture. These factors were analyzed using a two-tailed independent Student t test or the chi test for significance. Significant factors were further examined using logistic regression analysis. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate each parameter. RESULTS: Statistically significant differences were observed in ruptured and unruptured groups for aspect ratio, size ratio, height-width ratio, flow angle, aneurysm inclination angle, vessel angle, aneurysm shape, and aneurysm location. Logistic regression analysis further revealed that size ratio (OR 1.66; 95% CI 1.05 to 2.64), height width ratio (OR 14.22; 95% CI 2.67 to 75.88), aneurysm inclination angle (OR 1.04; 95% CI 1.01 to 1.07), aneurysm shape (OR 4.68; 95% CI 2.44 to 8.98), and aneurysm location (OR 1.60; 95% CI 1.15 to 2.23) had the strongest independent correlation with ruptured IA. The ROC analysis showed that the size ratio and flow angle had the highest area under the curve, with values of 0.735 and 0.730, respectively. CONCLUSIONS: Size ratio, height-width ratio, aneurysm inclination angle, aneurysm shape, and aneurysm location might be important for discriminating between ruptured and unruptured aneurysms. Further investigation will determine whether these morphological parameters and anatomical locations will be reliable predictors of aneurysm rupture. PMID- 26863106 TI - The 'pit-crew' model for improving door-to-needle times in endovascular stroke therapy: a Six-Sigma project. AB - BACKGROUND: Delays in delivering endovascular stroke therapy adversely affect outcomes. Time-sensitive treatments such as stroke interventions benefit from methodically developed protocols. Clearly defined roles in these protocols allow for parallel processing of tasks, resulting in consistent delivery of care. OBJECTIVE: To present the outcomes of a quality-improvement (QI) process directed at reducing stroke treatment times in a tertiary level academic medical center. METHODS: A Six-Sigma-based QI process was developed over a 3-month period. After an initial analysis, procedures were implemented and fine-tuned to identify and address rate-limiting steps in the endovascular care pathway. Prospectively recorded treatment times were then compared in two groups of patients who were treated 'before' (n=64) or 'after' (n=30) the QI process. Three time intervals were measured: emergency room (ER) to arrival for CT scan (ER-CT), CT scan to interventional laboratory arrival (CT-Lab), and interventional laboratory arrival to groin puncture (Lab-puncture). RESULTS: The ER-CT time was 40 (+/-29) min in the 'before' and 26 (+/-15) min in the 'after' group (p=0.008). The CT-Lab time was 87 (+/-47) min in the 'before' and 51 (+/-33) min in the 'after' group (p=0.0002). The Lab-puncture time was 24 (+/-11) min in the 'before' and 15 (+/ 4) min in the 'after' group (p<0.0001). The overall ER-arrival to groin-puncture time was reduced from 2 h, 31 min (+/-51) min in the 'before' to 1 h, 33 min (+/ 37) min in the 'after' group, (p<0.0001). The improved times were seen for both working hours and off-hours interventions. CONCLUSIONS: A protocol-driven process can significantly improve efficiency of care in time-sensitive stroke interventions. PMID- 26863107 TI - The Self-Reported Oral Health Status and Dental Attendance of Smokers and Non Smokers in England. AB - Smoking has been identified as the second greatest risk factor for global death and disability and has impacts on the oral cavity from aesthetic changes to fatal diseases such as oral cancer. The paper presents a secondary analysis of the National Adult Dental Health Survey (2009). The analysis used descriptive statistics, bivariate analyses and logistic regression models to report the self reported oral health status and dental attendance of smokers and non-smokers in England. Of the 9,657 participants, 21% reported they were currently smoking. When compared with smokers; non-smokers were more likely to report 'good oral health' (75% versus 57% respectively, p<0.05). Smokers were twice as likely to attend the dentist symptomatically (OR = 2.27, CI = 2.02-2.55) compared with non smoker regardless the deprivation status. Smokers were more likely to attend symptomatically in the most deprived quintiles (OR = 1.99, CI = 1.57-2.52) and perceive they had poorer oral health (OR = 1.77, CI = 1.42-2.20). The present research is consistent with earlier sub-national research and should be considered when planning early diagnosis and management strategies for smoking related conditions, considering the potential impact dental teams might have on smoking rates. PMID- 26863108 TI - Family Structure as a Correlate of Organized Sport Participation among Youth. AB - Organized sport is one way that youth participate in physical activity. There are disparities in organized sport participation by family-related factors. The purpose of this study was to determine whether non-traditional family structure and physical custody arrangements are associated with organized sport participation in youth, and if so whether this relationship is mediated by socioeconomic status. Data were from the 2009-10 Health Behaviour in School-aged Children survey, a nationally representative cross-section of Canadian youth in grades 6-10 (N = 21,201). Information on family structure was derived from three survey items that asked participants the number of adults they lived with, their relationship to these adults, and if applicable, how often they visited another parent outside their home. Participants were asked whether or not they were currently involved in an organized sport. Logistic regression was used to compare the odds of organized sport participation according to family structure. Bootstrap-based mediation analysis was used to assess mediation by perceived family wealth. The results indicated that by comparison to traditional families, boys and girls from reconstituted families with irregular visitation of a second parent, reconstituted families with regular visitation of a second parent, single parent families with irregular visitation of a second parent, and single-parent families with regular visitation of a second parent were less likely to participate in organized sport than those from traditional families, with odds ratios ranging from 0.48 (95% confidence interval: 0.38-0.61) to 0.78 (95% confidence interval: 0.56-1.08). The relationship between family structure and organized sport was significantly mediated by perceived family wealth, although the magnitude of the mediation was modest (ie, <20% change in effect estimate). In conclusion, youth living in both single-parent and reconstituted families experienced significant disparities in organized sport participation that was partially mediated by perceived family wealth. PMID- 26863109 TI - Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis. AB - BACKGROUND: The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. OBJECTIVE: To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. METHODS: A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. RESULTS: We established two novel observer independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. CONCLUSIONS: Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis. PMID- 26863111 TI - Serum angiogenic profile in abnormal placentation. AB - OBJECTIVE: To evaluate the circulating soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) levels in women with abnormal placentation and to compare the data with the results of women with normal pregnancy. MATERIAL AND METHODS: Serum biomarkers of angiogenesis and maternal and perinatal characteristics of 68 pregnant women, all in the third trimester, who were diagnosed to have vaginal bleeding due to complete placenta previa with and without concomitant placenta accreta, increta and percreta as the study group and 30 pregnant women without any placentation abnormality who eventually delivered at >=37 weeks of gestational age as the control group were evaluated. RESULTS: There was no statistical difference in the maternal serum values of sFlt1, PlGF, sFlt1/PlGF ratio and VEGF in groups with placental abnormality as compared to controls. Not even a single case of preeclampsia and intrauterine fetal growth restriction was encountered in the study group. CONCLUSION: We demonstrated that regardless of the localization and the degree of the myometrial invasion of the placenta in the uterus, the circulatory biomarkers of angiogenesis and vascularization were comparable. PMID- 26863112 TI - Surgical management of an odontogenic tumor in a banded Gila monster (Heloderma suspectum cinctum) with a novel herpesvirus. PMID- 26863113 TI - Multidentate Polymer Coatings for Compact and Homogeneous Quantum Dots with Efficient Bioconjugation. AB - Quantum dots are fluorescent nanoparticles used to detect and image proteins and nucleic acids. Compared with organic dyes and fluorescent proteins, these nanocrystals have enhanced brightness, photostability, and wavelength tunability, but their larger size limits their use. Recently, multidentate polymer coatings have yielded stable quantum dots with small hydrodynamic dimensions (<=10 nm) due to high-affinity, compact wrapping around the nanocrystal. However, this coating technology has not been widely adopted because the resulting particles are frequently heterogeneous and clustered, and conjugation to biological molecules is difficult to control. In this article we develop new polymeric ligands and optimize coating and bioconjugation methodologies for core/shell CdSe/Cd(x)Zn(1 x)S quantum dots to generate homogeneous and compact products. We demonstrate that "ligand stripping" to rapidly displace nonpolar ligands with hydroxide ions allows homogeneous assembly with multidentate polymers at high temperature. The resulting aqueous nanocrystals are 7-12 nm in hydrodynamic diameter, have quantum yields similar to those in organic solvents, and strongly resist nonspecific interactions due to short oligoethylene glycol surfaces. Compared with a host of other methods, this technique is superior for eliminating small aggregates identified through chromatographic and single-molecule analysis. We also demonstrate high-efficiency bioconjugation through azide-alkyne click chemistry and self-assembly with hexa-histidine-tagged proteins that eliminate the need for product purification. The conjugates retain specificity of the attached biomolecules and are exceptional probes for immunofluorescence and single molecule dynamic imaging. These results are expected to enable broad utilization of compact, biofunctional quantum dots for studying crowded macromolecular environments such as the neuronal synapse and cellular cytoplasm. PMID- 26863114 TI - Lead Contamination in Flint--An Abject Failure to Protect Public Health. PMID- 26863115 TI - Sequestration of Vascular Endothelial Growth Factor (VEGF) Induces Late Restrictive Lung Disease. AB - RATIONALE: Neonatal respiratory distress syndrome is a restrictive lung disease characterized by surfactant deficiency. Decreased vascular endothelial growth factor (VEGF), which demonstrates important roles in angiogenesis and vasculogenesis, has been implicated in the pathogenesis of restrictive lung diseases. Current animal models investigating VEGF in the etiology and outcomes of RDS require premature delivery, hypoxia, anatomically or temporally limited inhibition, or other supplemental interventions. Consequently, little is known about the isolated effects of chronic VEGF inhibition, started at birth, on subsequent developing lung structure and function. OBJECTIVES: To determine whether inducible, mesenchyme-specific VEGF inhibition in the neonatal mouse lung results in long-term modulation of AECII and whole lung function. METHODS: Triple transgenic mice expressing the soluble VEGF receptor sFlt-1 specifically in the mesenchyme (Dermo-1/rtTA/sFlt-1) were generated and compared to littermate controls at 3 months to determine the impact of neonatal downregulation of mesenchymal VEGF expression on lung structure, cell composition and function. Reduced tissue VEGF bioavailability has previously been demonstrated with this model. MEASUREMENTS AND MAIN RESULTS: Triple transgenic mice demonstrated restrictive lung pathology. No differences in gross vascular development or protein levels of vascular endothelial markers was noted, but there was a significant decrease in perivascular smooth muscle and type I collagen. Mutants had decreased expression levels of surfactant protein C and hypoxia inducible factor 1-alpha without a difference in number of type II pneumocytes. CONCLUSIONS: These data show that mesenchyme-specific inhibition of VEGF in neonatal mice results in late restrictive disease, making this transgenic mouse a novel model for future investigations on the consequences of neonatal RDS and potential interventions. PMID- 26863116 TI - An Appraisal of Proliferation and Apoptotic Markers in Papillary Thyroid Carcinoma: An Automated Analysis. AB - INTRODUCTION: Proliferation and apoptosis are opposing processes by which the cell numbers are kept in a delicate balance, essential for tissue homeostasis, whereas uncontrolled growth of cells is a hallmark of cancer. Papillary thyroid cancer (PTC) is the commonest type of thyroid cancer, with some PTC following an indolent course, whereas the other ones are more aggressive. AIM: To evaluate respective contribution of proliferation and apoptosis in the tumorigenesis of PTC by automated analysis. MATERIALS AND METHODS: We investigated the immunolabeling of phosphorylated histone H3 (pHH3), cyclin D1, active caspase-3, and bcl-2 in thirteen cases each of metastatic PTC, follicular variant of PTC (FVPTC), papillary microcarcinoma (PMC) and well differentiated tumor of uncertain malignant potential (WDT-UMP). FVPTC cases comprised seven encapsulated and six unencapsulated cases. RESULTS: Proliferation, as assessed by pHH3 and cyclin D1 immunolabeling, was increased in all PTC variants, including the putative precursor lesion WDT-UMP, compared to normal thyroid tissue. pHH3 was immunolabeled in more cells of metastatic PTC than of PMC and of encapsulated FVPTC. Surprisingly, metastatic PTC and unencapsulated FVPTC also demonstrated more cleaved caspase-3 immunolabeled cells than the other types. In contrast, increased expression of bcl-2 protein was seen in normal thyroid areas, encapsulated FVPTC and PMC as compared to metastatic PTC. Metastatic PTC shows higher proliferation than other types of PTC but unexpectedly also higher apoptotic levels. Similar results were also seen with unencapsulated FVPTC, thus suggesting that unencapsulated FVPTC has a potential for adverse outcome. Bcl-2 was immunolabeled in a low percentage of cells in WDT-UMP. CONCLUSIONS: The expression of the proliferative protein pHH3 together with the apoptotic marker cleaved caspase-3 may indicate an aggressive behaviour of PTC and loss of apoptosis inhibition by bcl-2 protein can further amplify the role of these proteins in tumor progression. Both cyclin D1 and bcl-2 could prove to be interesting markers of PTC precursor lesions. Automated/digital image quantification approach helps in refining the diagnostic accuracy. PMID- 26863117 TI - DIFFERENTIAL SUSCEPTIBILITY OF HUMAN SP-B GENETIC VARIANTS ON LUNG INJURY CAUSED BY BACTERIAL PNEUMONIA AND THE EFFECT OF A CHEMICALLY MODIFIED CURCUMIN. AB - Staphylococcus aureus is a common cause of nosocomial pneumonia frequently resulting in acute respiratory distress syndrome (ARDS). Surfactant protein B (SP B) gene expresses two proteins involved in lowering surface tension and host defense. Genotyping studies demonstrate a significant association between human SP-B genetic variants and ARDS. Curcumins have been shown to attenuate host inflammation in many sepsis models. Our hypothesis is that functional differences of SP-B variants and treatment with curcumin (CMC2.24) modulate lung injury in bacterial pneumonia. Humanized transgenic mice, expressing either SP-B T or C allele without mouse SP-B gene, were used. Bioluminescent labeled S. aureus Xen 36 (50 MUL) was injected intratracheally to cause pneumonia. Infected mice received daily CMC2.24 (40 mg/kg) or vehicle alone by oral gavage. Dynamic changes of bacteria were monitored using in vivo imaging system. Histological, cellular, and molecular indices of lung injury were studied in infected mice 48 h after infection. In vivo imaging analysis revealed total flux (bacterial number) was higher in the lung of infected SP-B-C mice compared with infected SP-B-T mice (P < 0.05). Infected SP-B-C mice demonstrated increased mortality, lung injury, apoptosis, and NF-kappaB expression compared with infected SP-B-T mice. Compared with controls, CMC2.24 treatment significantly reduced the following: mortality, total bacterial flux and lung tissue apoptosis, inflammatory cells, NF-kappaB expression (P < 0.05), and MMPs-2, -9, -12 activities (P < 0.05). We conclude that mice with SP-B-C allele are more susceptible to S. aureus pneumonia than mice with SP-B-T allele, and that CMC2.24 attenuates lung injury thus reducing mortality. PMID- 26863119 TI - ISCHEMIC CONDITIONING PROTECTS THE MICROCIRCULATION, PRESERVES ORGAN FUNCTION, AND PROLONGS SURVIVAL IN SEPSIS. AB - Ischemic conditioning induces a series of cellular modifications that may prevent injury from further hypoxic episodes, but there are few data in sepsis. In this randomized controlled study, we evaluated the effects of ischemic conditioning on the microcirculation, organ function, and survival time in an ovine model of septic shock.Sepsis was induced in 14 anesthetized, mechanically ventilated adult sheep by injecting autologous feces into the abdominal cavity. Animals were then randomized to ischemic pre- and post-conditioning or no conditioning (both n = 7). Remote ischemic conditioning was performed by inflating the balloon of a catheter in the aortic bifurcation for 2 min, followed by a 4-min deflation period. The procedure was performed four times before sepsis induction and 4 hourly afterward. Animals were followed until death or for a maximum of 30 h. Hemodynamic, oxygenation, and microcirculatory variables were monitored. The conditioned group had higher mixed venous oxygen saturation from 8 h after randomization, higher cardiac index, and oxygen delivery from 16 h, and higher mean arterial pressure and lower lactate levels from 20 h. They also had greater renal blood flow, urine output, and creatinine clearance. Microcirculatory variables were better preserved in the conditioned than in the control group from 6 h after randomization: the median proportion of perfused vessels was 91 (89 93)% versus 89 (86-90)% (P = 0.024) and there was less heterogeneity. Oliguria, hypotension, and death occurred later in the conditioned than in the control group. In this sepsis model, remote ischemic pre- and post-conditioning therefore decreased organ dysfunction, preserved the microcirculation, and prolonged survival. PMID- 26863120 TI - Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) Outperforms Serum Creatinine in Detecting Sepsis-Induced Acute Kidney Injury, Experiments on Bilateral Nephrectomy and Bilateral Ureter Obstruction Mouse Models. AB - Serum neutrophil gelatinase associated lipocalin (sNGAL), a promising acute kidney injury (AKI) biomarker produced by renal and non-renal tissues, might be affected by sepsis. We evaluated sNGAL in zero glomerular filtration rate models [bilateral ureter obstruction (BUO) and bilateral nephrectomy (BiNx)] with subsequent cecal ligation and puncture (CLP)-induced sepsis in 6 to 8-week-old ICR mice. We found that sNGAL increased earlier than serum creatinine (Scr) in BiNx/BUO with and without CLP. The earliest time-point of increased sNGAL in BiNx+CLP was 1 h after surgery. Scr, but not sNGAL, was lower at 18 h after BiNx/BUO+CLP compared with BiNx/BUO alone. Compared with BUO, BiNx had higher, and equal sNGAL at 1 to 18 h and 36 h, respectively. Additionally, similar NGAL expression in internal organs (heart, lung, liver, and spleen) and survival rates indicated the comparable severity of BiNx and BUO. Serum interleukin (IL)-6 was increased and correlated with sNGAL in BiNx/BUO with and without sepsis. In summary, we demonstrated: sNGAL is an early AKI biomarker, which is not affected by sepsis; sNGAL is mainly produced by extrarenal sources as demonstrated by the comparable sNGAL in BiNx and BUO; the saturation of renal NGAL re-absorption in BUO is demonstrated by lower sNGAL in BUO at 1 to 18 h, but not at 36 h when compared with BiNx; and a correlation of sNGAL and IL-6 implied sNGAL is a good sepsis prognostic biomarker. Therefore, sNGAL is a more beneficial sepsis-AKI biomarker than Scr. PMID- 26863118 TI - The Shift of an Intestinal "Microbiome" to a "Pathobiome" Governs the Course and Outcome of Sepsis Following Surgical Injury. AB - Sepsis following surgical injury remains a growing and worrisome problem following both emergent and elective surgery. Although early resuscitation efforts and prompt antibiotic therapy have improved outcomes in the first 24 to 48 h, late onset sepsis is now the most common cause of death in modern intensive care units. This time shift may be, in part, a result of prolonged exposure of the host to the stressors of critical illness which, over time, erode the health promoting intestinal microbiota and allow for virulent pathogens to predominate. Colonizing pathogens can then subvert the immune system and contribute to the deterioration of the host response. Here, we posit that novel approaches integrating the molecular, ecological, and evolutionary dynamics of the evolving gut microbiome/pathobiome during critical illness are needed to understand and prevent the late onset sepsis that develops following prolonged critical illness. PMID- 26863121 TI - Early Trauma-Induced Coagulopathy is Associated with Increased Ventilator Associated Pneumonia in Spinal Cord Injury Patients. AB - INTRODUCTION: Early trauma-induced coagulopathy may increase susceptibility to nosocomial infections such as ventilator-associated pneumonia. However, the relationship between trauma- induced coagulopathy and the development of ventilator-associated pneumonia in spinal cord injury patients has not been evaluated. METHODS: We conducted a 5-year retrospective study of 300 spinal cord injury patients admitted to Level 1 trauma center. Standard coagulation studies were evaluated upon arrival, prior to fluid resuscitative efforts, and at 24 h after admission. Based on these studies, three groups of patients were identified: no coagulopathy, latent coagulopathy, and admission coagulopathy. Ventilator- associated pneumonia was identified utilizing Centers for Disease Control and Prevention criteria. Since we used the data in the trauma registry and did not have the information on FiO2 and PEEP, we elected to use the VAP terminology and not the VAE sequence. Demographic, injury, and clinical characteristics were compared among no coagulopathy, latent coagulopathy, and admission coagulopathy groups using chi-square test and ANOVA for categorical and continuous variables, respectively. A logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between coagulopathy and both ventilator-associated pneumonia and mortality. RESULTS: The incidence of ventilator-associated pneumonia was 54.5% (OR 4.01, 95% CI 1.76 9.15) in spinal cord injury patients with admission coagulopathy, compared with the 17.5% in spinal cord injury patients with no coagulopathy. Mortality was significantly higher in spinal cord injury patients with admission coagulopathy than in spinal cord injury patients with no coagulopathy (OR 6.14, 95% CI 1.73 21.73).After adjusting for age, race, injury mechanism, Injury Severity Score, base deficit at admission, the number of pRBC units transfused in the first 24 h, and hospital stay, only the association of ventilator-associated pneumonia among those with admission coagulopathy remained significant (OR 3.51, 95% CI 1.48-8.32). Compared with those with no coagulopathy, patients with admission coagulopathy had a higher odds of death (4.10, 95% CI 1.53-11.02), though this association lost significance after adjustment (OR 3.56, 95% CI 0.90-14.12). There was no statistical difference in mortality for latent coagulopathy compared with no coagulopathy patients. CONCLUSION: Coagulopathy on admission in patients with spinal cord injury is associated with a statistically significant increase in ventilator-associated pneumonia incidence. Additional research is warranted to further characterize this association. PMID- 26863122 TI - PROGNOSTIC VALUE OF PLASMA TIGHT-JUNCTION PROTEINS FOR SEPSIS IN EMERGENCY DEPARTMENT: AN OBSERVATIONAL STUDY. AB - BACKGROUND: Studies have illustrated that the breakdown of tight junction (TJ) contributed to an increase in vascular permeability in response to stimulation of inflammatory cytokines. Additionally, the release of TJ-associated proteins into the circulation was observed in many diseases. The present study was designed to investigate whether plasma levels of TJ-associated proteins could serve as predictors of severity and clinical outcome of sepsis. METHODS: In total, 51 septic patients were enrolled. The peripheral blood samples were collected for each patient on emergency department arrival. Plasma levels of occludin (OCLN), claudins (CLDN)-5, and zonula occludens (ZO)-1 and serum levels of procalcitonin (PCT) and lactate were measured. In addition, APACHE II score as well as SOFA score was calculated. The prognostic values of OCLN, CLDN-5, and ZO-1 were compared with the first 24-h maximum APACHE II score and SOFA score. RESULTS: The median levels of OCLN and ZO-1 were elevated with sepsis severity. The levels of plasma OCLN and ZO-1 were positively correlated with APACHE II score, SOFA score as well as lactate levels of the patients. The levels of ZO-1 revealed valuable diagnostic capacity to diagnose MODS, and the areas under the receiver-operating characteristic (AUC) curves of ZO-1 were similar to those of lactate levels, but better than those of PCT levels. The prognostic value for in-hospital mortality of ZO-1 was comparable to that of lactate levels, APACHE II score, and SOFA score, and superior to OCLN or PCT. CONCULSIONS: OCLN and ZO1 levels appear to be early prognostic markers in patients suffering from sepsis. PMID- 26863123 TI - Peptidomic Analysis of Rat Plasma: Proteolysis in Hemorrhagic Shock. AB - It has been previously shown that intestinal proteases translocate into the circulation during hemorrhagic shock and contribute to proteolysis in distal organs. However, consequences of this phenomenon have not previously been investigated using high-throughput approaches. Here, a shotgun label-free quantitative proteomic approach was utilized to compare the peptidome of plasma samples from healthy and hemorrhagic shock rats to verify the possible role of uncontrolled proteolytic activity in shock. Plasma was collected from rats after hemorrhagic shock (HS) consisting of 2-h hypovolemia followed by 2-h reperfusion, and from healthy control (CTRL) rats. A new two-step enrichment method was applied to selectively extract peptides and low molecular weight proteins from plasma, and directly analyze these samples by tandem mass spectrometry. One hundred twenty-six circulating peptides were identified in CTRL and 295 in HS animals. Ninety-six peptides were present in both conditions; of these, 57 increased and 30 decreased in shock. In total, 256 peptides were increased or present only in HS confirming a general increase in proteolytic activity in shock. Analysis of the proteases that potentially generated the identified peptides suggests that the larger relative contribution to the proteolytic activity in shock is due to chymotryptic-like proteases. These results provide quantitative confirmation that extensive, system-wide proteolysis is part of the complex pathologic phenomena occurring in hemorrhagic shock. PMID- 26863124 TI - Neuronal Nitric Oxide Synthase is Involved in Vascular Hyporeactivity and Multiple Organ Dysfunction Associated with Hemorrhagic Shock. AB - Severe hemorrhage can lead to global ischemia and hemorrhagic shock (HS), resulting in multiple organ failure (MOF) and death. Restoration of blood flow and re-oxygenation is associated with an exacerbation of tissue injury and inflammatory response. The neuronal nitric oxide synthase (nNOS) has been implicated in vascular collapse and systemic inflammation of septic shock; however, the role of nNOS in HS is poorly understood. The aim of this study was to evaluate the role of nNOS in the MOF associated with HS.Rats were subjected to HS under anesthesia. Mean arterial pressure was reduced to 30 mmHg for 90 min, followed by resuscitation with shed blood. Rats were randomly treated with two chemically distinct nNOS inhibitors [ARL 17477 (1 mg/kg) and 7-nitroindazol (5 mg/kg)] or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed.HS was associated with MOF development. Inhibition of nNOS activity at resuscitation protected rats against the MOF and vascular dysfunction. In addition, treatment of HS rats with nNOS inhibitors attenuated neutrophil infiltration into target organs and decreased the activation of NF-kappaB, iNOS expression, NO production, and nitrosylation of proteins. Furthermore, nNOS inhibition also reduced the levels of pro inflammatory cytokines TNF-alpha and IL-6 in HS rats.In conclusion, two distinct inhibitors of nNOS activity reduced the MOF, vascular dysfunction, and the systemic inflammation associated with HS. Thus, nNOS inhibitors may be useful as an adjunct therapy before fluids and blood administration in HS patients to avoid the MOF associated with reperfusion injury during resuscitation. PMID- 26863125 TI - THE EPITHELIUM AS A TARGET IN SEPSIS. AB - Organ dysfunction induced by sepsis has been consistently associated with worse outcome and death. Regardless of the organ compromised, epithelial dysfunction is present throughout the body, affecting those organs that contain epithelia like the skin, lungs, liver, gut, and kidneys. Despite their obvious differences, sepsis seems to alter common features of all epithelia, such as barrier function and vectorial ion transport. Such alterations in the lung, the gut, and the kidney have direct implications that may explain the profound organ functional impairments in the absence of overt cell death. Epithelial injury in this context is not only an explanatory real pathophysiologic event, but also represents a source of biomarkers that have been explored to identify organ compromise earlier, predict outcome, and even to test novel therapeutic interventions such as blood purification. However, this remains largely experimental, and despite promising results, work is still required to better understand the response of the epithelial cells to sepsis, to define their role in adaptation to insults, to comprehend the interorgan cross-talk that occurs in these circumstances, and to exploit these aspects in pursuit of targeted therapies like blood purification, which may improve outcome for these patients in the future. PMID- 26863126 TI - Polytrauma Increases Susceptibility to Pseudomonas Pneumonia in Mature Mice. AB - Pneumonia is the most common complication observed in patients with severe injuries. Although the average age of injured patients is 47 years, existing studies of the effect of injury on the susceptibility to infectious complications have focused on young animals, equivalent to a late adolescent human. We hypothesized that mature adult animals are more susceptible to infection after injury than younger counterparts. To test this hypothesis, we challenged 6 to 8 month-old mature mice to a polytrauma injury followed by Pseudomonas aeruginosa pneumonia and compared them to young (8-10-week-old) animals. We demonstrate that polytrauma injury increases mortality from pneumonia in mature animals (sham pneumonia 21% vs. polytrauma-pneumonia 62%) but not younger counterparts. After polytrauma, pneumonia in mature mice is associated with higher bacterial burden in lung, increased incidence of bacteremia, and elevated levels of bacteria in the blood, demonstrating that injury decreases the ability to control the infectious challenge. We further find that polytrauma did not induce elevations in circulating cytokine levels (TNF-alpha, IL-6, KC, and IL-10) 24 h after injury. However, mature mice subjected to polytrauma demonstrated an exaggerated circulating inflammatory cytokine response to subsequent Pseudomonas pneumonia. Additionally, whereas prior injury increases LPS-stimulated IL-6 production by peripheral blood leukocytes from young (8-10-week-old) mice, injury does not prime IL-6 production by cell from mature adult mice. We conclude that in mature mice polytrauma results in increased susceptibility to Pseudomonas pneumonia while priming an exaggerated but ineffective inflammatory response. PMID- 26863127 TI - Can Early Aggressive Administration of Fresh Frozen Plasma Improve Outcomes in Patients with Severe Blunt Trauma?--A Report by the Japanese Association for the Surgery of Trauma. AB - BACKGROUND: This study investigated the effect of a high ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) within the first 6 and 24 h after admission on mortality in patients with severe, blunt trauma. METHODS: This retrospective observational study included 189 blunt trauma patients with an Injury Severity Score (ISS) >=16 requiring RBC transfusions within the first 24 h. Receiver operating characteristic (ROC) curve analysis was performed to calculate cut-off values of the FFP/RBC ratio for outcome. The patients were then divided into two groups according to the cut-off value. Patient survival was compared between groups using propensity score matching (PSM). RESULTS: The area under the ROC curve was 0.57, and the FFP/RBC ratio was 1.0 at maximum sensitivity (0.57) and specificity (0.67). All patients were then divided into two groups (FFP/RBC ratio >=1 or <1) and analyzed using PSM and inverse probability of treatment weighting (IPTW). The unadjusted hazard ratio (HR) was 0.44, and the adjusted HR was 0.29. The HR was 0.38 by PSM and 0.41 by IPTW. The survival rate was significantly higher in patients with an FFP/RBC ratio >=1 within the first 6 h. CONCLUSIONS: Severe blunt trauma patients transfused with an FFP/RBC ratio >=1 within the first 6 h had an HR of about 0.4. The transfusion of an FFP/RBC ratio >=1 within the first 6 h was associated with the outcomes of blunt trauma patients with ISS >=16 who need a transfusion within 24 h. PMID- 26863128 TI - Physical Isolation of Endospores from Environmental Samples by Targeted Lysis of Vegetative Cells. AB - Endospore formation is a survival strategy found among some bacteria from the phylum Firmicutes. During endospore formation, these bacteria enter a morpho physiological resting state that enhances survival under adverse environmental conditions. Even though endospore-forming Firmicutes are one of the most frequently enriched and isolated bacterial groups in culturing studies, they are often absent from diversity studies based on molecular methods. The resistance of the spore core is considered one of the factors limiting the recovery of DNA from endospores. We developed a method that takes advantage of the higher resistance of endospores to separate them from other cells in a complex microbial community using physical, enzymatic and chemical lysis methods. The endospore-only preparation thus obtained can be used for re-culturing or to perform downstream analysis such as tailored DNA extraction optimized for endospores and subsequent DNA sequencing. This method, applied to sediment samples, has allowed the enrichment of endospores and after sequencing, has revealed a large diversity of endospore-formers in freshwater lake sediments. We expect that the application of this method to other samples will yield a similar outcome. PMID- 26863129 TI - Isolation of Infiltrating Leukocytes from Mouse Skin Using Enzymatic Digest and Gradient Separation. AB - Dissociating murine skin into a single cell suspension is essential for downstream cellular analysis such as the characterization of infiltrating immune cells in rodent models of skin inflammation. Here, we describe a protocol for the digestion of mouse skin in a nutrient-rich solution with collagenase D, followed by separation of hematopoietic cells using a discontinuous density gradient. Cells thus obtained can be used for in vitro studies, in vivo transfer, and other downstream cellular and molecular analyses including flow cytometry. This protocol is an effective and economical alternative to expensive mechanical dissociators, specialized separation columns, and harsher trypsin- and dispase based digestion methods, which may compromise cellular viability or density of surface proteins relevant for phenotypic characterization or cellular function. As shown here in our representative data, this protocol produced highly viable cells, contained specific immune cell subsets, and had no effect on integrity of common surface marker proteins used in flow cytometric analysis. PMID- 26863130 TI - Target Fortification of Breast Milk: Predicting the Final Osmolality of the Feeds. AB - For preterm infants, it is common practice to add human milk fortifiers to native breast milk to enhance protein and calorie supply because the growth rates and nutritional requirements of preterm infants are considerably higher than those of term infants. However, macronutrient intake may still be inadequate because the composition of native breast milk has individual inter- and intra-sample variation. Target fortification (TFO) of breast milk is a new nutritional regime aiming to reduce such variations by individually measuring and adding deficient macronutrients. Added TFO components contribute to the final osmolality of milk feeds. It is important to predict the final osmolality of TFO breast milk to ensure current osmolality recommendations are followed to minimize feeding intolerance and necrotizing enterocolitis. This study aims to develop and validate equations to predict the osmolality of TFO milk batches. To establish prediction models, the osmolalities of either native or supplemented breast milk with known amounts of fat, protein, and carbohydrates were analyzed. To validate prediction models, the osmolalities of each macronutrient and combinations of macronutrients were measured in an independent sample set. Additionally, osmolality was measured in TFO milk samples obtained from a previous clinical study and compared with predicted osmolality using the prediction equations. Following the addition of 1 g of carbohydrates (glucose polymer), 1 g of hydrolyzed protein, or 1 g of whey protein per 100 mL breast milk, the average increase in osmolality was 20, 38, and 4 mOsm/kg respectively. Adding fat decreased osmolality only marginally due to dilution effect. Measured and predicted osmolality of combinations of macronutrients as well as single macronutrient (R2 = 0.93) were highly correlated. Using clinical data (n = 696), the average difference between the measured and predicted osmolality was 3 +/- 11 mOsm/kg and was not statistically significant. In conclusion, the prediction model can be utilized to estimate osmolality values after fortification. PMID- 26863131 TI - Response to the Letter by Kosker et al. Entitled 'Choroidal Changes in Patients with Familial Mediterranean Fever'. PMID- 26863132 TI - Baculovirus IE2 Stimulates the Expression of Heat Shock Proteins in Insect and Mammalian Cells to Facilitate Its Proper Functioning. AB - Baculoviruses have gained popularity as pest control agents and for protein production in insect systems. These viruses are also becoming popular for gene expression, tissue engineering and gene therapy in mammalian systems. Baculovirus infection triggers a heat shock response, and this response is crucial for its successful infection of host insect cells. However, the viral protein(s) or factor(s) that trigger this response are not yet clear. Previously, we revealed that IE2-an early gene product of the baculovirus-could form unique nuclear bodies for the strong trans-activation of various promoters in mammalian cells. Here, we purified IE2 nuclear bodies from Vero E6 cells and investigated the associated proteins by using mass spectrometry. Heat shock proteins (HSPs) were found to be one of the major IE2-associated proteins. Our experiments show that HSPs are greatly induced by IE2 and are crucial for the trans-activation function of IE2. Interestingly, blocking both heat shock protein expression and the proteasome pathway preserved the IE2 protein and its nuclear body structure, and revived its function. These observations reveal that HSPs do not function directly to assist the formation of the nuclear body structure, but may rather protect IE2 from proteasome degradation. Aside from functional studies in mammalian cells, we also show that HSPs were stimulated and required to determine IE2 protein levels, in insect cells infected with baculovirus. Upon inhibiting the expression of heat shock proteins, baculovirus IE2 was substantially suppressed, resulting in a significantly suppressed viral titer. Thus, we demonstrate a unique feature in that IE2 can function in both insect and non-host mammalian cells to stimulate HSPs, which may be associated with IE2 stabilization and lead to the protection of the its strong gene activation function in mammalian cells. On the other hand, during viral infection in insect cells, IE2 could also strongly stimulate HSPs and ultimately affect viral replication. PMID- 26863133 TI - Serial Change in Cervical Length for the Prediction of Emergency Cesarean Section in Placenta Previa. AB - PURPOSE: To evaluate whether serial change in cervical length (CL) over time can be a predictor for emergency cesarean section (CS) in patients with placenta previa. METHODS: This was a retrospective cohort study of patients with placenta previa between January 2010 and November 2014. All women were offered serial measurement of CL by transvaginal ultrasound at 19 to 23 weeks (CL1), 24 to 28 weeks (CL2), 29 to 31 weeks (CL3), and 32 to 34 weeks (CL4). We compared clinical characteristics, serial change in CL, and outcomes between the emergency CS group (case group) and elective CS group (control group). The predictive value of change in CL for emergency CS was evaluated. RESULTS: A total of 93 women were evaluated; 31 had emergency CS due to massive vaginal bleeding. CL tended to decrease with advancing gestational age in each group. Until 29-31 weeks, CL showed no significant differences between the two groups, but after that, CL in the emergency CS group decreased abruptly, even though CL in the elective CS group continued to gradually decrease. On multivariate analysis to determine risk factors, only admissions for bleeding (odds ratio, 34.710; 95% CI, 5.239-229.973) and change in CL (odds ratio, 3.522; 95% CI, 1.210-10.253) were significantly associated with emergency CS. Analysis of the receiver operating characteristic curve showed that change in CL could be the predictor of emergency CS (area under the curve 0.734, p < 0.001), with optimal cutoff for predicting emergency cesarean delivery of 6.0 mm. CONCLUSIONS: Previous admission for vaginal bleeding and change in CL are independent predictors of emergency CS in placenta previa. Women with change in CL more than 6 mm between the second and third trimester are at high risk of emergency CS in placenta previa. Single measurements of short CL at the second or third trimester do not seem to predict emergency CS. PMID- 26863134 TI - Assessing the efficacy of co-inoculation of wheat seedlings with the associative bacteria Paenibacillus polymyxa 1465 and Azospirillum brasilense Sp245. AB - Co-inoculation of associative bacteria, which have high nitrogen-fixing activity, tolerance for environmental conditions, and the ability to compete with the natural microflora, is used widely to enhance the growth and yields of agricultural plants. We evaluated the ability of 2 co-inoculated plant-growth promoting rhizobacteria, Paenibacillus polymyxa 1465 and Azospirillum brasilense Sp245, to colonize roots of wheat (Triticum aestivum L. 'Saratovskaya 29') seedlings, and we assessed the morphometric parameters of wheat early in its development. Analysis by ELISA with polyclonal antibodies raised against the exopolysaccharide of P. polymyxa 1465 and the lipopolysaccharide of A. brasilense Sp245 demonstrated that the root-colonizing activity of A. brasilense was higher when the bacterium was co-inoculated with P. polymyxa than when it was inoculated singly. Immunofluorescence microscopy with Alexa Fluor 532-labeled antibodies revealed sites of attachment of co-inoculated P. polymyxa and A. brasilense and showed that the 2 bacteria colonized similar regions of the roots. Co-inoculation exerted a negative effect on wheat seedling development, inhibiting root length by 17.6%, total root weight by 11%, and total shoot weight by 12%. Under certain conditions, dual inoculation of wheat may prove ineffective, apparently owing to the competition between the rhizobacteria for colonization sites on the plant roots. The findings from this study may aid in developing techniques for mixed bacterial inoculation of cultivated plants. PMID- 26863135 TI - HIV Infection and the Epidemiology of Invasive Pneumococcal Disease (IPD) in South African Adults and Older Children Prior to the Introduction of a Pneumococcal Conjugate Vaccine (PCV). AB - INTRODUCTION: Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV) programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD) in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use. METHODS: National, active, laboratory based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES) hospital sites, clinical data, including HIV serostatus, were collected from IPD patients >= 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI) in 2009. RESULTS: In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons >= 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734) of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000), with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190). HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV) than HIV-infected persons (39% (210/544) vs. 19% (790/4190), p<0.001). During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1). CONCLUSION: Seventy to eighty five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection) for pneumococcal vaccination. These data describe the epidemiology of IPD amongst HIV-infected and -uninfected adults during the pre-PCV era and provide a robust baseline to calculate the indirect effect of PCV in future studies. PMID- 26863137 TI - Prestroke Antiplatelet Agents in First-Time Ischemic Stroke Are Related to Subtypes. AB - BACKGROUND: It is not well known whether prestroke antiplatelet agents (PAs) are associated with the subtypes of ischemic stroke. METHODS: We screened patients in a hospital-based stroke registry. Patients who were admitted with a diagnosis of first-time ischemic stroke within 5 days of symptom onset were included. Ischemic stroke subtypes were classified in accordance with the Trial of ORG 10172 in Acute Stroke Treatment classification based on stroke mechanism: large-artery atherosclerosis (LA), cardioembolism (CE), small vessel occlusion (SVO), other determined (OC) or undetermined causes (UC). Multinomial logistic regression analyses were performed to evaluate the effect of PA on stroke subtypes before and after propensity score matching. RESULTS: Among 3,025 patients, 748 (24.7%) were taking antiplatelet agents prior to stroke. After propensity score matching, 1,190 patients were ultimately included. The PA group was associated with strokes caused by SVO rather than LA in multinomial logistic regression of an unmatched dataset. However, multivariable analysis after propensity score matching demonstrated that PA use was associated with a higher probability of SVO and CE (OR 2.05, p < 0.001 and OR 1.62, p = 0.05, respectively) compared with LA. CONCLUSIONS: PAs were associated with specific index stroke subtypes. PMID- 26863136 TI - In Silico Analysis of the Structural and Biochemical Features of the NMD Factor UPF1 in Ustilago maydis. AB - The molecular mechanisms regulating the accuracy of gene expression are still not fully understood. Among these mechanisms, Nonsense-mediated Decay (NMD) is a quality control process that detects post-transcriptionally abnormal transcripts and leads them to degradation. The UPF1 protein lays at the heart of NMD as shown by several structural and functional features reported for this factor mainly for Homo sapiens and Saccharomyces cerevisiae. This process is highly conserved in eukaryotes but functional diversity can be observed in various species. Ustilago maydis is a basidiomycete and the best-known smut, which has become a model to study molecular and cellular eukaryotic mechanisms. In this study, we performed in silico analysis to investigate the structural and biochemical properties of the putative UPF1 homolog in Ustilago maydis. The putative homolog for UPF1 was recognized in the annotated genome for the basidiomycete, exhibiting 66% identity with its human counterpart at the protein level. The known structural and functional domains characteristic of UPF1 homologs were also found. Based on the crystal structures available for UPF1, we constructed different three-dimensional models for umUPF1 in order to analyze the secondary and tertiary structural features of this factor. Using these models, we studied the spatial arrangement of umUPF1 and its capability to interact with UPF2. Moreover, we identified the critical amino acids that mediate the interaction of umUPF1 with UPF2, ATP, RNA and with UPF1 itself. Mutating these amino acids in silico showed an important effect over the native structure. Finally, we performed molecular dynamic simulations for UPF1 proteins from H. sapiens and U. maydis and the results obtained show a similar behavior and physicochemical properties for the protein in both organisms. Overall, our results indicate that the putative UPF1 identified in U. maydis shows a very similar sequence, structural organization, mechanical stability, physicochemical properties and spatial organization in comparison to the NMD factor depicted for Homo sapiens. These observations strongly support the notion that human and fungal UPF1 could perform equivalent biological activities. PMID- 26863138 TI - Protein Expression Profiling of Giant Cell Tumors of Bone Treated with Denosumab. AB - Giant cell tumors of bone (GCTB) are locally aggressive osteolytic bone tumors. Recently, some clinical trials have shown that denosumab is a novel and effective therapeutic option for aggressive and recurrent GCTB. This study was performed to investigate the molecular mechanism underlying the therapeutic effect of denosumab. Comparative proteomic analyses were performed using GCTB samples which were taken before and after denosumab treatment. Each expression profile was analyzed using the software program to further understand the affected biological network. One of identified proteins was further evaluated by gelatin zymography and an immunohistochemical analysis. We identified 13 consistently upregulated proteins and 19 consistently downregulated proteins in the pre- and post denosumab samples. Using these profiles, the software program identified molecular interactions between the differentially expressed proteins that were indirectly involved in the RANK/RANKL pathway and in several non-canonical subpathways including the Matrix metalloproteinase pathway. The data analysis also suggested that the identified proteins play a critical functional role in the osteolytic process of GCTB. Among the most downregulated proteins, the activity of MMP-9 was significantly decreased in the denosumab-treated samples, although the residual stromal cells were found to express MMP-9 by an immunohistochemical analysis. The expression level of MMP-9 in the primary GCTB samples was not correlated with any clinicopathological factors, including patient outcomes. Although the replacement of tumors by fibro-osseous tissue or the diminishment of osteoclast-like giant cells have been shown as therapeutic effects of denosumab, the residual tumor after denosumab treatment, which is composed of only stromal cells, might be capable of causing bone destruction; thus the therapeutic application of denosumab would be still necessary for these lesions. We believe that the protein expression patterns and the results of the network analysis will provide a better understanding of the effects of denosumab administration in patients with GCTB. PMID- 26863139 TI - Sample Size Reassessment and Hypothesis Testing in Adaptive Survival Trials. AB - Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. An alternative test incorporating all event times is found, where a conservative assumption must be made in order to guarantee type I error control. We examine the power of this approach using the example of a clinical trial comparing two cancer therapies. PMID- 26863140 TI - Electrocardiogram ST-Segment Morphology Delineation Method Using Orthogonal Transformations. AB - Differentiation between ischaemic and non-ischaemic transient ST segment events of long term ambulatory electrocardiograms is a persisting weakness in present ischaemia detection systems. Traditional ST segment level measuring is not a sufficiently precise technique due to the single point of measurement and severe noise which is often present. We developed a robust noise resistant orthogonal transformation based delineation method, which allows tracing the shape of transient ST segment morphology changes from the entire ST segment in terms of diagnostic and morphologic feature-vector time series, and also allows further analysis. For these purposes, we developed a new Legendre Polynomials based Transformation (LPT) of ST segment. Its basis functions have similar shapes to typical transient changes of ST segment morphology categories during myocardial ischaemia (level, slope and scooping), thus providing direct insight into the types of time domain morphology changes through the LPT feature-vector space. We also generated new Karhunen and Lo eve Transformation (KLT) ST segment basis functions using a robust covariance matrix constructed from the ST segment pattern vectors derived from the Long Term ST Database (LTST DB). As for the delineation of significant transient ischaemic and non-ischaemic ST segment episodes, we present a study on the representation of transient ST segment morphology categories, and an evaluation study on the classification power of the KLT- and LPT-based feature vectors to classify between ischaemic and non ischaemic ST segment episodes of the LTST DB. Classification accuracy using the KLT and LPT feature vectors was 90% and 82%, respectively, when using the k Nearest Neighbors (k = 3) classifier and 10-fold cross-validation. New sets of feature-vector time series for both transformations were derived for the records of the LTST DB which is freely available on the PhysioNet website and were contributed to the LTST DB. The KLT and LPT present new possibilities for human expert diagnostics, and for automated ischaemia detection. PMID- 26863141 TI - Inhibitory Control, but Not Prolonged Object-Related Experience Appears to Affect Physical Problem-Solving Performance of Pet Dogs. AB - Human infants develop an understanding of their physical environment through playful interactions with objects. Similar processes may influence also the performance of non-human animals in physical problem-solving tasks, but to date there is little empirical data to evaluate this hypothesis. In addition or alternatively to prior experiences, inhibitory control has been suggested as a factor underlying the considerable individual differences in performance reported for many species. Here we report a study in which we manipulated the extent of object-related experience for a cohort of dogs (Canis familiaris) of the breed Border Collie over a period of 18 months, and assessed their level of inhibitory control, prior to testing them in a series of four physical problem-solving tasks. We found no evidence that differences in object-related experience explain variability in performance in these tasks. It thus appears that dogs do not transfer knowledge about physical rules from one physical problem-solving task to another, but rather approach each task as a novel problem. Our results, however, suggest that individual performance in these tasks is influenced in a complex way by the subject's level of inhibitory control. Depending on the task, inhibitory control had a positive or a negative effect on performance and different aspects of inhibitory control turned out to be the best predictors of individual performance in the different tasks. Therefore, studying the interplay between inhibitory control and problem-solving performance will make an important contribution to our understanding of individual and species differences in physical problem-solving performance. PMID- 26863142 TI - Strong Selection at MHC in Mexicans since Admixture. AB - Mexicans are a recent admixture of Amerindians, Europeans, and Africans. We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP, and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the genome, which is the hallmark of recent selection for admixed samples. The estimated selection coefficients are 0.05 and 0.07 for two datasets, which put our finding among the strongest known selections observed in humans, namely, lactase selection in northern Europeans and sickle-cell trait in Africans. Using inaccurate Amerindian training samples was a major concern for the credibility of previously reported selection signals in Latinos. Taking advantage of the flexibility of our statistical model, we devised a model fitting technique that can learn Amerindian ancestral haplotype from the admixed samples, which allows us to infer local ancestries for Mexicans using only European and African training samples. The strong selection signal at the MHC remains without Amerindian training samples. Finally, we note that medical history studies suggest such a strong selection at MHC is plausible in Mexicans. PMID- 26863143 TI - The Creative Stereotype Effect. AB - Because of its fundamental relevance to scientific innovation, artistic expression, and human ingenuity, creativity has long been the subject of systematic psychological investigation. Concomitantly, the far-reaching effects of stereotypes on various cognitive and social processes have been widely researched. Bridging these two literatures, we show in a series of two studies that stereotypes related to creativity can both enhance and diminish individuals' performance on a divergent thinking task. Specifically, Study 1 demonstrated that participants asked to take on a stereotypically uninhibited perspective performed significantly better on a divergent thinking task than those participants who took on a stereotypically inhibited perspective, and a control group. Relatedly, Study 2 showed that the same effect is found within-subjects, with divergent thinking significantly improving when participants invoke an uninhibited stereotype. Moreover, we demonstrate the efficacy of Latent Semantic Analysis as an objective measure of the originality of ideas, and discuss implications of our findings for the nature of creativity. Namely, that creativity may not be best described as a stable individual trait, but as a malleable product of context and perspective. PMID- 26863144 TI - Fluctuating Minds: Spontaneous Psychophysical Variability during Mind-Wandering. AB - Mind-wandering is the occasional distraction we experience while performing a cognitive task. It arises without any external precedent, varies over time, and interferes with the processing of sensory information. Here, we asked whether the transition from the on-task state to mind-wandering is a gradual process or an abrupt event. We developed a new experimental approach, based on the continuous, online assessment of individual psychophysical performance. Probe questions were asked whenever response times (RTs) exceeded 2 standard deviations from the participant's average RT. Results showed that mind-wandering reports were generally preceded by slower RTs, as compared to trials preceding on-task reports. Mind-wandering episodes could be reliably predicted from the response time difference between the last and the second-to-last trials. Thus, mind wandering reports follow an abrupt increase in behavioral variability, lasting between 2.5 and 10 seconds. PMID- 26863145 TI - Cost-Analysis of Seven Nosocomial Outbreaks in an Academic Hospital. AB - OBJECTIVES: Nosocomial outbreaks, especially with (multi-)resistant microorganisms, are a major problem for health care institutions. They can cause morbidity and mortality for patients and controlling these costs substantial amounts of funds and resources. However, how much is unclear. This study sets out to provide a comparable overview of the costs of multiple outbreaks in a single academic hospital in the Netherlands. METHODS: Based on interviews with the involved staff, multiple databases and stored records from the Infection Prevention Division all actions undertaken, extra staff employment, use of resources, bed-occupancy rates, and other miscellaneous cost drivers during different outbreaks were scored and quantified into Euros. This led to total costs per outbreak and an estimated average cost per positive patient per outbreak day. RESULTS: Seven outbreaks that occurred between 2012 and 2014 in the hospital were evaluated. Total costs for the hospital ranged between ?10,778 and ?356,754. Costs per positive patient per outbreak day, ranged between ?10 and ?1,369 (95% CI: ?49-?1,042), with a mean of ?546 and a median of ?519. Majority of the costs (50%) were made because of closed beds. CONCLUSIONS: This analysis is the first to give a comparable overview of various outbreaks, caused by different microorganisms, in the same hospital and all analyzed with the same method. It shows a large variation within the average costs due to different factors (e.g. closure of wards, type of ward). All outbreaks however cost considerable amounts of efforts and money (up to ?356,754), including missed revenue and control measures. PMID- 26863146 TI - Comparison of manual therapy and exercise therapy for postural hyperkyphosis: A randomized clinical trial. AB - OBJECTIVE: To compare the efficacy of a manual therapy and an exercise therapy program in improving postural hyperkyphosis among young adults. METHODS: Forty six women between the ages of 18 to 30 years with thoracic kyphosis diagnosed by flexicurve ruler were randomly assigned to either an exercise therapy or a manual therapy group. The exercise therapy program focused on stretching and strengthening exercises in 15 sessions over 5 weeks. The manual therapy group received 15 sessions of manual techniques including massage, mobilization, muscle energy and myofascial release. Kyphosis angle and back extensor muscle strength were measured with a motion analysis system and a dynamometer at the baseline and after treatment. The data were analyzed with paired and independent t-tests. RESULTS: After treatment, the angle of thoracic kyphosis was smaller and back extensor muscle strength was significantly greater in both the exercise and manual therapy groups (p < 0.001). We found no significant differences between groups in the changes in kyphosis angle or muscle strength after treatment (p > 0.05). CONCLUSION: Manual therapy was as effective as exercise therapy in reducing kyphosis angle and increasing back extensor muscle strength in young women with postural hyperkyphosis. PMID- 26863147 TI - High-Field MRI Reveals a Drastic Increase of Hypoxia-Induced Microhemorrhages upon Tissue Reoxygenation in the Mouse Brain with Strong Predominance in the Olfactory Bulb. AB - Human pathophysiology of high altitude hypoxic brain injury is not well understood and research on the underlying mechanisms is hampered by the lack of well-characterized animal models. In this study, we explored the evolution of brain injury by magnetic resonance imaging (MRI) and histological methods in mice exposed to normobaric hypoxia at 8% oxygen for 48 hours followed by rapid reoxygenation and incubation for further 24 h under normoxic conditions. T2*-, diffusion-weighted and T2-relaxometry MRI was performed before exposure, immediately after 48 hours of hypoxia and 24 hours after reoxygenation. Cerebral microhemorrhages, previously described in humans suffering from severe high altitude cerebral edema, were also detected in mice upon hypoxia-reoxygenation with a strong region-specific clustering in the olfactory bulb, and to a lesser extent, in the basal ganglia and cerebral white matter. The number of microhemorrhages determined immediately after hypoxia was low, but strongly increased 24 hours upon onset of reoxygenation. Histologically verified microhemorrhages were exclusively located around cerebral microvessels with disrupted interendothelial tight junction protein ZO-1. In contrast, quantitative T2 and apparent-diffusion-coefficient values immediately after hypoxia and after 24 hours of reoxygenation did not show any region-specific alteration, consistent with subtle multifocal but not with regional or global brain edema. PMID- 26863148 TI - Optical Control of Living Cells Electrical Activity by Conjugated Polymers. AB - Hybrid interfaces between organic semiconductors and living tissues represent a new tool for in-vitro and in-vivo applications. In particular, conjugated polymers display several optimal properties as substrates for biological systems, such as good biocompatibility, excellent mechanical properties, cheap and easy processing technology, and possibility of deposition on light, thin and flexible substrates. These materials have been employed for cellular interfaces like neural probes, transistors for excitation and recording of neural activity, biosensors and actuators for drug release. Recent experiments have also demonstrated the possibility to use conjugated polymers for all-optical modulation of the electrical activity of cells. Several in-vitro study cases have been reported, including primary neuronal networks, astrocytes and secondary line cells. Moreover, signal photo-transduction mediated by organic polymers has been shown to restore light sensitivity in degenerated retinas, suggesting that these devices may be used for artificial retinal prosthesis in the future. All in all, light sensitive conjugated polymers represent a new approach for optical modulation of cellular activity. In this work, all the steps required to fabricate a bio-polymer interface for optical excitation of living cells are described. The function of the active interface is to transduce the light stimulus into a modulation of the cell membrane potential. As a study case, useful for in-vitro studies, a polythiophene thin film is used as the functional, light absorbing layer, and Human Embryonic Kidney (HEK-293) cells are employed as the biological component of the interface. Practical examples of successful control of the cell membrane potential upon stimulation with light pulses of different duration are provided. In particular, it is shown that both depolarizing and hyperpolarizing effects on the cell membrane can be achieved depending on the duration of the light stimulus. The reported protocol is of general validity and can be straightforwardly extended to other biological preparations. PMID- 26863149 TI - Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent. AB - Eravacycline is an investigational, synthetic fluorocycline antibacterial agent that is structurally similar to tigecycline with two modifications to the D-ring of its tetracycline core: a fluorine atom replaces the dimethylamine moiety at C 7 and a pyrrolidinoacetamido group replaces the 2-tertiary-butyl glycylamido at C 9. Like other tetracyclines, eravacycline inhibits bacterial protein synthesis through binding to the 30S ribosomal subunit. Eravacycline demonstrates broad spectrum antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with the exception of Pseudomonas aeruginosa. Eravacycline is two- to fourfold more potent than tigecycline versus Gram-positive cocci and two- to eightfold more potent than tigecycline versus Gram-negative bacilli. Intravenous eravacycline demonstrates linear pharmacokinetics that have been described by a four-compartment model. Oral bioavailability of eravacycline is estimated at 28 % (range 26-32 %) and a single oral dose of 200 mg achieves a maximum plasma concentration (C max) and area under the plasma concentration-time curve from 0 to infinity (AUC0-infinity) of 0.23 +/- 0.04 mg/L and 3.34 +/- 1.11 mg.h/L, respectively. A population pharmacokinetic study of intravenous (IV) eravacycline demonstrated a mean steady-state volume of distribution (V ss) of 320 L or 4.2 L/kg, a mean terminal elimination half-life (t 1/2) of 48 h, and a mean total clearance (CL) of 13.5 L/h. In a neutropenic murine thigh infection model, the pharmacodynamic parameter that demonstrated the best correlation with antibacterial response was the ratio of area under the plasma concentration-time curve over 24 h to the minimum inhibitory concentration (AUC0-24h/MIC). Several animal model studies including mouse systemic infection, thigh infection, lung infection, and pyelonephritis models have been published and demonstrated the in vivo efficacy of eravacycline. A phase II clinical trial evaluating the efficacy and safety of eravacycline in the treatment of community-acquired complicated intra-abdominal infection (cIAI) has been published as well, and phase III clinical trials in cIAI and complicated urinary tract infection (cUTI) have been completed. The eravacycline phase III program, known as IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline), investigated its safety and efficacy in cIAI (IGNITE 1) and cUTI (IGNITE 2). Eravacycline met the primary endpoint in IGNITE 1, while data analysis for IGNITE 2 is currently ongoing. Common adverse events reported in phase I-III studies included gastrointestinal effects such as nausea and vomiting. Eravacycline is a promising intravenous and oral fluorocycline that may offer an alternative treatment option for patients with serious infections, particularly those caused by multidrug-resistant Gram negative pathogens. PMID- 26863150 TI - Au-Interaction of Slp1 Polymers and Monolayer from Lysinibacillus sphaericus JG B53 - QCM-D, ICP-MS and AFM as Tools for Biomolecule-metal Studies. AB - In this publication the gold sorption behavior of surface layer (S-layer) proteins (Slp1) of Lysinibacillus sphaericus JG-B53 is described. These biomolecules arrange in paracrystalline two-dimensional arrays on surfaces, bind metals, and are thus interesting for several biotechnical applications, such as biosorptive materials for the removal or recovery of different elements from the environment and industrial processes. The deposition of Au(0) nanoparticles on S layers, either by S-layer directed synthesis or adsorption of nanoparticles, opens new possibilities for diverse sensory applications. Although numerous studies have described the biosorptive properties of S-layers, a deeper understanding of protein-protein and protein-metal interaction still remains challenging. In the following study, inductively coupled mass spectrometry (ICP MS) was used for the detection of metal sorption by suspended S-layers. This was correlated to measurements of quartz crystal microbalance with dissipation monitoring (QCM-D), which allows the online detection of proteinaceous monolayer formation and metal deposition, and thus, a more detailed understanding on metal binding. The ICP-MS results indicated that the binding of Au(III) to the suspended S-layer polymers is pH dependent. The maximum binding of Au(III) was obtained at pH 4.0. The QCM-D investigations enabled the detection of Au(III) sorption as well as the deposition of Au(0)-NPs in real-time during the in situ experiments. Further, this method allowed studying the influence of metal binding on the protein lattice stability of Slp1. Structural properties and protein layer stability could be visualized directly after QCM-D experiment using atomic force microscopy (AFM). In conclusion, the combination of these different methods provides a deeper understanding of metal binding by bacterial S-layer proteins in suspension or as monolayers on either bacterial cells or recrystallized surfaces. PMID- 26863151 TI - The work-based predictors of job engagement and job satisfaction experienced by community health professionals. AB - BACKGROUND: Job engagement represents a critical resource for community-based health care agencies to achieve high levels of effectiveness. However, studies examining the organizational sources of job engagement among health care professionals have generally overlooked those workers based in community settings. PURPOSE: This study drew on the demand-control model, in addition to stressors that are more specific to community health services (e.g., unrewarding management practices), to identify conditions that are closely associated with the engagement experienced by a community health workforce. Job satisfaction was also included as a way of assessing how the predictors of job engagement differ from those associated with other job attitudes. METHODOLOGY/APPROACH: Health and allied health care professionals (n = 516) from two Australian community health services took part in the current investigation. Responses from the two organizations were pooled and analyzed using linear multiple regression. FINDINGS: The analyses revealed that three working conditions were predictive of both job engagement and job satisfaction (i.e., job control, quantitative demands, and unrewarding management practices). There was some evidence of differential effects with cognitive demands being associated with job engagement, but not job satisfaction. PRACTICE IMPLICATIONS: The results provide important insights into the working conditions that, if addressed, could play key roles in building a more engaged and satisfied community health workforce. Furthermore, working conditions like job control and management practices are amenable to change and thus represent important areas where community health services could enhance the energetic and motivational resources of their employees. PMID- 26863153 TI - Pediatric neurocritical care in the 21st century: from empiricism to evidence. AB - PURPOSE OF REVIEW: Approximately one in five children admitted to a pediatric ICU have a new central nervous system injury or a neurological complication of their critical illness. The spectrum of neurologic insults in children is diverse and clinical practice is largely empirical, as few randomized, controlled trials have been reported. This lack of data poses a substantial challenge to the practice of pediatric neurocritical care (PNCC). PNCC has emerged as a novel subspecialty, and its presence is expanding within tertiary care centers. This review highlights the recent advances in the field, with a focus on traumatic brain injury (TBI), cardiac arrest, and stroke as disease models. RECENT FINDINGS: Variable approaches to the structure of a PNCC service have been reported, comprising multidisciplinary teams from neurology, critical care, neurosurgery, neuroradiology, and anesthesia. Neurologic morbidity is substantial in critically ill children and the increased use of continuous electroencephalography monitoring has highlighted this burden. Therapeutic hypothermia has not proven effective for treatment of children with severe TBI or out-of-hospital cardiac arrest. However, results of studies of severe TBI suggest that multidisciplinary care in the ICU and adherence to guidelines for care can reduce mortality and improve outcome. SUMMARY: There is an unmet need for clinicians with expertise in the practice of brain-directed critical care for children. Although much of the practice of PNCC may remain empiric, a focus on the regionalization of care, creating defined training paths, practice within multidisciplinary teams, protocol-directed care, and improved measures of long-term outcome to quantify the impact of such care can provide evidence to direct the maturation of this field. PMID- 26863152 TI - Development and Delivery of a Physical Activity Intervention for People With Huntington Disease: Facilitating Translation to Clinical Practice. AB - BACKGROUND AND PURPOSE: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process. METHODS: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training. RESULTS: Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was L30,773 ($47,042 USD). DISCUSSION AND CONCLUSIONS: An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A122). PMID- 26863154 TI - High molecular weight DNA assembly in vivo for synthetic biology applications. AB - DNA assembly is the key technology of the emerging interdisciplinary field of synthetic biology. While the assembly of smaller DNA fragments is usually performed in vitro, high molecular weight DNA molecules are assembled in vivo via homologous recombination in the host cell. Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae are the main hosts used for DNA assembly in vivo. Progress in DNA assembly over the last few years has paved the way for the construction of whole genomes. This review provides an update on recent synthetic biology advances with particular emphasis on high molecular weight DNA assembly in vivo in E. coli, B. subtilis and S. cerevisiae. Special attention is paid to the assembly of whole genomes, such as those of the first synthetic cell, synthetic yeast and minimal genomes. PMID- 26863155 TI - Effect of Resveratrol-Based Nutritional Supplement on Choroidal Thickness: A Pilot Study. AB - PURPOSE: The effect of an oral trans-resveratrol-based supplement (Longevinex(r)) on choroidal thickness, measured using optical coherence tomography (OCT) enhanced depth imaging, was investigated in a prospective study. MATERIALS AND METHODS: 34 young, healthy participants were randomly divided into two age- and gender-matched groups. They were then assigned in a randomized fashion to treat with either a trans-resveratrol-based group (Longevinex(r), Las Vegas) or placebo. All participants underwent ocular imaging with spectral domain (SD)-OCT (Spectralis; Heidelberg Engineering, Heidelberg) at the baseline and then again 1 h following treatment. The choroidal thickness was measured in a masked fashion at the fovea and at four additional points, located at 500 MUm and 1000 MUm nasal to the fovea and 500 MUm and 1000 MUm temporal to the fovea. RESULTS: In the resveratrol group, the foveal choroidal thickness at the baseline was 267.73 +/- 84.19 MUm (mean +/- SD); it increased to 284.57 +/- 92.39 MUm 1 h after drug treatment (p = 0.033). The mean choroidal thickness was also significantly increased at each of the four extrafoveal points (all p < 0.05). In the control group, the mean baseline choroidal thickness at the fovea was 269.73 +/- 71.40 MUm (mean +/- SD) and it was 268.43 +/- 70.15 MUm (mean +/- SD) 1 h after the placebo was administered (p = 0.183); there were also no significant differences in choroidal thickness at the four additional points (all p > 0.05) Conclusion: A significant increase in choroidal thickness following oral administration of a trans-resveratrol-based supplement was observed. There was no change in choroidal thickness in the placebo-treated control group. We speculate that the increased choroidal thickness is the result of choroidal vessel vasodilation. PMID- 26863156 TI - Spatiotemporal Mapping of Motility in Ex Vivo Preparations of the Intestines. AB - Multiple approaches have been used to record and evaluate gastrointestinal motility including: recording changes in muscle tension, intraluminal pressure, and membrane potential. All of these approaches depend on measurement of activity at one or multiple locations along the gut simultaneously which are then interpreted to provide a sense of overall motility patterns. Recently, the development of video recording and spatiotemporal mapping (STmap) techniques have made it possible to observe and analyze complex patterns in ex vivo whole segments of colon and intestine. Once recorded and digitized, video records can be converted to STmaps in which the luminal diameter is converted to grayscale or color [called diameter maps (Dmaps)]. STmaps can provide data on motility direction (i.e., stationary, peristaltic, antiperistaltic), velocity, duration, frequency and strength of contractile motility patterns. Advantages of this approach include: analysis of interaction or simultaneous development of different motility patterns in different regions of the same segment, visualization of motility pattern changes over time, and analysis of how activity in one region influences activity in another region. Video recordings can be replayed with different timescales and analysis parameters so that separate STmaps and motility patterns can be analyzed in more detail. This protocol specifically details the effects of intraluminal fluid distension and intraluminal stimuli that affect motility generation. The use of luminal receptor agonists and antagonists provides mechanistic information on how specific patterns are initiated and how one pattern can be converted into another pattern. The technique is limited by the ability to only measure motility that causes changes in luminal diameter, without providing data on intraluminal pressure changes or muscle tension, and by the generation of artifacts based upon experimental setup; although, analysis methods can account for these issues. When compared to previous techniques the video recording and STmap approach provides a more comprehensive understanding of gastrointestinal motility. PMID- 26863157 TI - Enhanced X-ray absorption for micro-CT analysis of low density polymers. AB - X-ray microtomography (micro-CT), one of the most resourceful instruments for high resolution 3D analysis, can provide qualitative and quantitative accurate structural and compositional information for a broad range of materials. Yet its contribution to the field of biopolymeric materials science is often limited by low imaging contrast due to scarce X-ray attenuation features, particularly for sponges and foam-like structures. This limitation can be overcome to some extent by adjusting the working parameters of micro-CT equipment. However, such approach also facilitates noise and artefacts, and solving the signal-to-noise trade-off has been always problematic. Searching for alternatives turns one's attention towards the improvement of X-ray attenuation features. While several studies report the use of contrast agents for biological materials, studies to integrate multiple micro-CT approaches for biopolymers were not conducted so far. This method paper is thus aimed to serve as a platform for micro-CT analysis of low X ray absorptive polymers. Here, several contrast enhancing artifices were developed and trialled on gelatin and poly(vinyl alcohol) biopolymer composites (GP). Accordingly, GP were modified with iodine, barium, silver-based chemicals and hexa(methyl disilazane) by two different methods, i.e. addition of high atomic number chemicals during materials synthesis and post-synthesis staining, respectively. Consequently, cross-sectional scanning electron microscopy emerged as complementary characterization, aimed to confirm the reproducibility of samples morphological features. The most versatile methods were barium chloride additive incorporation and iodine staining coupled with hexa(methyl disilazane) chemical drying. Both methods significantly improved the X-ray absorbance of our polymeric samples, providing better contrast of micro-CT tomograms. PMID- 26863158 TI - [Outcomes of Stage-Adapted Surgical Treatment of Pleural Empyema]. AB - BACKGROUND: The surgical treatment of pleural empyema should be carried out depending on the stage of the disease and the patient's symptoms. The aim of this study was to evaluate the outcomes of surgical pleural empyema treatment. PATIENTS AND METHODS: Retrospective analysis of all patients with pleural empyema treated surgically between January 2008 and December 2013. The primary endpoint of the study was inpatient lethality. Secondary endpoints included duration of inpatient stay, type of treatment (surgical/conservative), proof of pathogen and type, alteration and duration of antibiotic therapy. RESULTS: Of 359 patients, 0.8 % (n = 3) had stage I empyema, 50.4 % (n = 181) had stage II and 48.7 % (n = 175) had stage III. The most frequent causes (32.4 %) included acute pneumonia (parapneumonic pleural empyema), surgery (usually thoracic) in 18.0 % of cases and previous pneumonia (postpneumonic pleural empyema) in 15.4 %. Surgery was performed in 86 % of cases (operative procedures: open thoracotomy 85 %, VATS 15 %). The average duration of inpatient stay was 20 days for stages II and III. Recovery following VATS was significantly shorter in stage II compared to thoracotomy (p = 0.022). Hospital lethality amounted to 7.0 % (25 patients). The lethality rate was 5.5 % (10/185) in stage II and 8.6 % (15/175) in stage III. Patients with confirmed pathogens had a significantly worse mortality rate across all stages (9.8 %) than patients with no confirmed pathogens (4.0 %, p = 0.034). Age, malignant underlying disease, multiple comorbidities, immunosuppression, a change in antibiotic regimens and sepsis were significant risk factors. CONCLUSION: The inpatient lethality of patients with pleural empyema correlates with the stage of the condition. Positive confirmation of pathogens, sepsis, a higher age, multiple comorbidities, malignant tumour disease, immunosuppression and a change of antibiotics are negative prognostic factors. PMID- 26863159 TI - A robust adaptive denoising framework for real-time artifact removal in scalp EEG measurements. AB - OBJECTIVE: Non-invasive measurement of human neural activity based on the scalp electroencephalogram (EEG) allows for the development of biomedical devices that interface with the nervous system for scientific, diagnostic, therapeutic, or restorative purposes. However, EEG recordings are often considered as prone to physiological and non-physiological artifacts of different types and frequency characteristics. Among them, ocular artifacts and signal drifts represent major sources of EEG contamination, particularly in real-time closed-loop brain-machine interface (BMI) applications, which require effective handling of these artifacts across sessions and in natural settings. APPROACH: We extend the usage of a robust adaptive noise cancelling (ANC) scheme ([Formula: see text] filtering) for removal of eye blinks, eye motions, amplitude drifts and recording biases simultaneously. We also characterize the volume conduction, by estimating the signal propagation levels across all EEG scalp recording areas due to ocular artifact generators. We find that the amplitude and spatial distribution of ocular artifacts vary greatly depending on the electrode location. Therefore, fixed filtering parameters for all recording areas would naturally hinder the true overall performance of an ANC scheme for artifact removal. We treat each electrode as a separate sub-system to be filtered, and without the loss of generality, they are assumed to be uncorrelated and uncoupled. MAIN RESULTS: Our results show over 95-99.9% correlation between the raw and processed signals at non-ocular artifact regions, and depending on the contamination profile, 40-70% correlation when ocular artifacts are dominant. We also compare our results with the offline independent component analysis and artifact subspace reconstruction methods, and show that some local quantities are handled better by our sample adaptive real-time framework. Decoding performance is also compared with multi day experimental data from 2 subjects, totaling 19 sessions, with and without [Formula: see text] filtering of the raw data. SIGNIFICANCE: The proposed method allows real-time adaptive artifact removal for EEG-based closed-loop BMI applications and mobile EEG studies in general, thereby increasing the range of tasks that can be studied in action and context while reducing the need for discarding data due to artifacts. Significant increase in decoding performances also justify the effectiveness of the method to be used in real-time closed-loop BMI applications. PMID- 26863160 TI - Deep brain stimulation for bipolar disorder-review and outlook. AB - Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment. PMID- 26863162 TI - Abstracts of Scientific Papers and Posters Presented at the Annual Meeting of the Association of Academic Physiatrists. PMID- 26863161 TI - Theoretical investigations on the magnetocaloric and electrical properties of a perovskite manganite La(0.67)Ba(0.1)Ca(0.23)MnO3. AB - An investigation of the magnetic, magnetocaloric and electrical behavior of La(0.67)Ba(0.1)Ca(0.23)MnO3 is presented. The variation of magnetization (M) vs. temperature (T) under 1, 2, 3, 4 and 5 T magnetic fields reveals a ferromagnetic paramagnetic transition. Magnetic entropy change, relative cooling power and specific heat for magnetic field variation were conducted using a phenomenological model. Moreover, the electrical resistivity is fitted with the phenomenological percolation model which is based on the phase segregation of ferromagnetic metallic clusters and paramagnetic insulating regions. The equation of the form DeltaS(P)(M)(T,H) = - alpha?(H)(0)[?(ln)(rho)/?(T)](H)(dH) relates the magnetic order to the transport behavior of our sample. The results show that the as obtained magnetic entropy change values are similar to those determined using data obtained from the investigation of the dependence of magnetization on the temperature and magnetic field. PMID- 26863163 TI - Strengthening prevention in primary care. PMID- 26863164 TI - The interface between primary health care and population health: challenges and opportunities for prevention. AB - Primary health care has the potential to contribute to population health at the individual and population levels. The '5As' (ask, assess, advise/agree, assist and arrange) provide a framework to realise this potential, especially for disadvantaged and vulnerable populations, not only by better organising multidisciplinary preventive interventions within primary health care, but also by linking these interventions with more intensive community and population programs and services, especially for patients with low health literacy. This requires changes to information systems to prompt and record preventive care, work with practices to engage a range of disciplines, including practice nurses, and development of effective linkages with other services in the local community. This has important implications for the newly established Primary Health Networks in supporting improvement within primary care, and creating linkages and partnerships with a range of organisations involved in delivering preventive interventions in the community. However, prevention in primary health care needs to be underpinned by funding systems that support multidisciplinary and preventive care for a population, rather than simply reactive, episode-based care. PMID- 26863165 TI - How integrating primary care and public health could improve population health outcomes: a view from Liverpool, UK. AB - Although primary care is at the forefront of delivering healthcare to the population, its role in preventing poor health has varied throughout history. Faced with growing demand on healthcare services and a rise in noncommunicable diseases, some health systems are attempting to integrate healthcare delivery with broader population health and wellbeing interventions. Liverpool has a rich history of taking action to improve population health; this paper discusses a range of interventions that have taken place across the city. There is a renewed opportunity to systematise approaches to primary and secondary prevention, strengthened by the lead that general practitioners now have in commissioning health services and their accountability for improved population health outcomes through clinical commissioning groups. This is strongly articulated in the Healthy Liverpool program, a city-wide plan for health and care services. This paper suggests that four key enablers strengthen delivery of public health priorities through primary care: maximising opportunities to identify risk factors for preventable disease, fully exploiting the data collected in primary care to plan and design services, responding to community needs and assets through community engagement, and addressing wider determinants of health through strong partnerships. PMID- 26863166 TI - The new Australian Primary Health Networks: how will they integrate public health and primary care? AB - On 1 July 2015, the Australian Government established 31 new Primary Health Networks (PHNs), following a review by its former Chief Medical Officer, John Horvath, of 61 Medicare Locals created under the previous Labor administration. The Horvath review recommended, among other things, that new, larger primary health organisations be established to reduce fragmentation of care by integrating and coordinating health services, supporting the role of general practice, and leveraging and administering health program funding. The two main objectives of the new PHNs, as stated on the Department of Health's website, are "increasing the efficiency and effectiveness of medical services for patients, particularly those at risk of poor health outcomes, and improving coordination of care to ensure patients receive the right care in the right place at the right time". Below are three viewpoints, commissioned for this primary health care themed issue of Public Health Research & Practice, from the Australian Government Department of Health, the Public Health Association of Australia and a Sydney based PHN. We asked the authors to focus particularly on how the newly established networks might help to integrate public health within the primary health care landscape. Our authors have pointed out the huge overlap between public health and primary care and looked at evidence showing the great benefits for health systems of collaboration between the two. Challenges ahead include a possible government focus on delivery of 'frontline' medical services, which may come at the expense of population health, and the complexity of dealing with all primary health care stakeholders, including health professionals, Local Health Districts, nongovernment organisations, research institutions and local communities. PMID- 26863167 TI - A guide to scaling up population health interventions. AB - The 'how to' of scaling up public health interventions for maximum reach and outcomes is receiving greater attention; however, there remains a paucity of practical tools to guide those actively involved in scaling up processes in high income countries. To fill this gap, the New South Wales Ministry of Health developed Increasing the scale of population health interventions: a guide (2014). The guide was informed by a systematic review of scaling up models and methods, and a two-round Delphi process with a sample of senior policy makers, practitioners and researchers actively involved in scaling up processes. Although it is a practical guide to assist health policy makers, health practitioners and others responsible for scaling up effective population health interventions, it can also be used by researchers in the design of research studies that are potentially suitable for scaling up, particularly where research-practice collaborations are involved. The guide is divided into four steps: step 1, 'scalability assessment', aims to determine if an intervention is scalable; step 2, 'developing a scale up plan', aims to develop a practical and workable scaling up plan that can be used to convince stakeholders there is a compelling case for action. Step 3, 'preparing for scale up', aims to identify ways of securing resources needed for going to scale, operating at scale, and building a foundation of legitimacy and support to sustain the scaling up effort through the implementation stage; and step 4, 'scaling up the intervention', involves putting the plan developed in step 2 into place. Although the guide is written as though the user is starting from the point of assessing the scalability of an intervention, later steps can be used by those already involved in scaling up to review their implementation processes. The guide is not intended to be prescriptive. Its purpose is to help policy makers, practitioners, researchers and other decision makers decide on appropriate methodological and practical choices, and balance what is desirable with what is feasible. PMID- 26863168 TI - Factors influencing reductions in smoking among Australian adolescents. AB - A continued increase in the proportion of adolescents who never smoke, as well as an understanding of factors that influence reductions in smoking among this susceptible population, is crucial. The World Health Organization Framework Convention on Tobacco Control provides an appropriate structure to briefly examine Australian and New South Wales policies and programs that are influencing reductions in smoking among adolescents in Australia. This paper provides an overview of price and recent tax measures to reduce the demand for tobacco, the evolution of smoke-free environment policies, changes to tobacco labelling and packaging, public education campaigns, and restrictions to curb tobacco advertising. It also discusses supplyreduction measures that limit adolescents' access to tobacco products. Consideration is given to emerging priorities to achieve continued declines in smoking by Australian adolescents. PMID- 26863169 TI - Impact of medical consultation frequency on risk factors and medications 6 months after acute coronary syndrome. AB - OBJECTIVE: Initiatives that support primary care to better enable delivery of optimal prevention services are of great importance. The purpose of this study was to examine the frequency of medical consultations by patients with acute coronary syndrome (ACS) in the 6 months after hospital discharge and to determine whether the frequency of visits was associated with differences in lifestyle, clinical measures and medication prescription. METHODS: We conducted a retrospective subgroup analysis of data collected in the Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events (CONCORDANCE), which is an ongoing (prospective) clinical initiative providing continuous real-time reporting on the clinical characteristics, management and outcomes of patients admitted to Australian hospitals with ACS. We compared clinical measures, medications, smoking status and receipt of cardiac rehabilitation with frequency of medical consultations 6 months after hospital discharge. RESULTS: Patients with ACS visited their general practitioner (GP) a mean of 4.4 (+/- 3.8) times and their cardiologist 1.2 (+/- 0.9) times in the 6 month period after their index admission. Patients who saw a GP in the 6-month period had significantly higher rates of participation in cardiac rehabilitation, receipt of dietary advice and prescription of cardioprotective medications. Factors associated with increased frequency of GP visits were older age groups (oldest fourth vs youngest fourth incidence rate ratio (IRR) 1.08; 95% CI 1.01, 1.14), being female (male vs female IRR 0.83; 95% CI 0.80, 0.86), diagnosis of ST segment elevation myocardial infarction (STEMI) (STEMI vs non-STEMI IRR 1.08; 95% CI 1.04, 1.13; STEMI vs unstable angina IRR 1.01; 95% CI 0.95, 1.06), being a current smoker (IRR 1.09; 95% CI 1.05, 1.15), history of cardiovascular disease (IRR 1.06; 95% CI 1.01, 1.12), history of diabetes (IRR 1.25; 95% CI 1.21, 1.31), inpatient revascularisation (IRR 0.95; 95% CI 0.91, 0.99), receipt of cardiac rehabilitation referral (IRR 0.93; 95% CI 0.89, 0.97), and discharged on four or more out of five indicated medications (IRR 1.04; 95% CI 1.00, 1.08). CONCLUSION: The majority of ACS survivors in this study saw their GP frequently and their cardiologist at least once during the 6 months after index admission. Seizing these opportunities to engage, manage and support patients is important for strengthening prevention in primary care. PMID- 26863170 TI - Breast cancer recurrence following active treatment: determining its incidence in the NSW population. AB - OBJECTIVES: It is important for consumers, clinicians and health service planners to know the risk of recurrence of primary breast cancer after initial treatment. At present, none of Australia's state or territory cancer registries routinely report this information. We aimed to determine the incidence of recurrence in New South Wales (NSW) clinical practice for the period 18 months to 6 years after diagnosis of primary breast cancer. STUDY TYPE: Retrospective cohort study using population-based linked health data. METHODS: We identified 2416 women in the 45 and Up Study who were diagnosed with primary invasive breast cancer between 2003 and 2008 in NSW, and who had not had a recurrence 18 months after diagnosis. Unit level hospital, pharmacy and outpatient medical claims were used to identify treatment for recurrence. Incidence of recurrence was calculated using individual person-time at risk (18 months to 6 years postdiagnosis), with follow-up censored for death or end of study period (median follow-up 3 years). Time to recurrence was calculated, and Cox proportional regression was used to identify women's baseline and active treatment characteristics that were predictive of recurrence up to 6 years postdiagnosis. RESULTS: 217 women (9%) had a hospital, pharmacy or outpatient claim indicating breast cancer recurrence. Overall annual incidence of recurrence was 3.3%. Recurrence rates were significantly higher for women with node-positive (4.8% vs 2.5% annually; hazard ratio [HR] = 1.7; 95% confidence interval [95% CI] 1.3, 2.3) or hormone receptor-negative tumours (3.8% vs 3.1% annually; HR = 1.3; 95% CI 1.0, 1.7). Women with tumours >2 cm at diagnosis were more likely to experience recurrence than women with smaller/unknown tumours (4.8% vs 2.7% annually; HR = 1.5; 95% CI 1.1, 2.0). CONCLUSIONS: A combination of routinely collected administrative health datasets can be used to determine recurrence rates, allowing future assessment of population-level changes over time and investigations of the real-world impact of specific treatments on outcomes. PMID- 26863171 TI - Variation in and factors associated with timing of low risk, pre-labour repeat caesarean sections in NSW, 2008-2011. AB - OBJECTIVE: To explore variation in public hospital rates of early (37-38 weeks gestation) prelabour repeat caesarean section among low-risk women at and beyond term in New South Wales (NSW) between 2008 and 2011. IMPORTANCE OF THE STUDY: A NSW Ministry of Health policy directive for public hospitals (PD2007_024), 'Maternity - timing of elective or pre-labour caesarean section', requires that low-risk elective or prelabour caesarean section does not occur before 39 completed weeks gestation. However, compliance with this policy has not been evaluated. STUDY TYPE: Population-based record linkage study Methods: Linked birth and hospital data for low-risk, prelabour repeat caesarean sections in NSW in 2008-2011 were analysed using multilevel regression modelling. Rates were adjusted for casemix and hospital factors. Low-risk pregnancies were defined as singleton live births at 37-42 weeks gestation among women without medical or obstetric complications and where the indication for caesarean section was 'elective repeat caesarean section'. RESULTS: In 2008-2011, there were 15 163 prelabour repeat caesarean sections among low-risk women in NSW. Overall, 34.7% of low-risk prelabour repeat caesarean sections occurred before 39 weeks gestation. Adjusted NSW public hospital rates of early (37-38 weeks gestation) low-risk prelabour repeat caesarean section varied widely (16.3-67.5%). Adjusting for casemix factors actually increased the between-hospital variation by 4.3%; adjusting for hospital factors reduced variation by 20.0%. Smoking, private healthcare, assisted reproductive technology use, higher parity, a noncaesarean uterine scar and delivering in a hospital with CPAP (continuous positive airway pressure) facilities were associated with higher odds of early delivery, although infants that were small for gestational age were associated with lower odds. Hospitals with higher rates of low-risk deliveries and higher propensity for vaginal birth after caesarean section had lower odds of early delivery. CONCLUSIONS: The findings suggest generally poor compliance with the policy directive that prelabour caesarean does not occur before 39 weeks gestation, with adjusted compliance rates ranging from 32.5% to 83.7%. Large between-hospital variation after adjustment suggests that nonmedical factors are related to timing of low-risk prelabour repeat caesarean sections. Further strategies are needed to improve adherence to this evidence based policy. PMID- 26863172 TI - Testing a health research instrument to develop a state-wide survey on maternity care. AB - Partnerships between researchers and end users are an important strategy for research uptake in policy and practice. This paper describes how collaboration between an academic research organisation (the Kolling Institute) and a government performance reporting agency (the New South Wales [NSW] Bureau of Health Information) contributed to the development of a new state-wide maternity care survey for NSW. PMID- 26863173 TI - Government to choose lead sites for mental health reform. PMID- 26863175 TI - Lifestyle modification program rolls out across Australia. PMID- 26863174 TI - My Health Record to deliver "new class" of data. PMID- 26863176 TI - Pyrrolic-nitrogen doped graphene: a metal-free electrocatalyst with high efficiency and selectivity for the reduction of carbon dioxide to formic acid: a computational study. AB - Searching for metal-free catalysts for the carbon dioxide reduction reaction (CO2RR) has been a key challenge in the electrosynthesis of fuels for CO2 utilization. In this work, we investigated the potential of N-doped graphene as the electrocatalyst of CO2RR by means of comprehensive density functional theory (DFT) computations. The computations revealed that N-doping can modify the electronic properties of graphene for enhancing the electrochemical reduction of CO2 into CO and HCOOH, resulting in a low free energy barrier for the potential limiting step to form the key intermediate COOH as well as the strong adsorption energy of adsorbed COOH and the weak adsorption energy of CO or HCOOH. The highest catalytic activity toward CO2RR is shown by pyrrolic N-doped graphene due to its lowest overpotential of 0.24 V among all N-doped graphenes, and leads exclusively to HCOOH as the product. Therefore, our results demonstrated that N doped graphene holds great promise as an electrocatalyst for the CO2RR with high efficiency and selectivity by suitably tuning its N species. PMID- 26863177 TI - A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail. AB - The arteriovenous fistula (AVF) still suffers from a high number of failures caused by insufficient remodeling and intimal hyperplasia from which the exact pathophysiology remains unknown. In order to unravel the pathophysiology a murine model of AVF-failure was developed in which the configuration of the anastomosis resembles the preferred situation in the clinical setting. A model was described in which an AVF is created by connecting the venous end of the branch of the external jugular vein to the side of the common carotid artery using interrupted sutures. At a histological level, we observed progressive stenotic intimal lesions in the venous outflow tract that is also seen in failed human AVFs. Although this procedure can be technically challenging due to the small dimensions of the animal, we were able to achieve a surgical success rate of 97% after sufficient training. The key advantage of a murine model is the availability of transgenic animals. In view of the different proposed mechanisms that are responsible for AVF failure, disabling genes that might play a role in vascular remodeling can help us to unravel the complex pathophysiology of AVF failure. PMID- 26863178 TI - C3 and 2D C3 Marfey's Methods for Amino Acid Analysis in Natural Products. AB - We validate the improved resolution and sensitivity of the C3 Marfey's method, including an ability to resolve all Ile isomers, against an array of amino acids commonly encountered in natural products and by comparison to an existing Marfey's method. We also describe an innovative 2D C3 Marfey's method as an analytical approach for determining the regiochemistry of enantiomeric amino acid residues in natural products. The C3 and 2D C3 Marfey's methods represent valuable tools for probing and defining the stereocomplexity of hydrolytically accessible amino acid residues in natural products. PMID- 26863181 TI - Aging Precursor Solution in High Humidity Remarkably Promoted Grain Growth in Cu2ZnSnS4 Films. AB - Earth-abundant Cu2ZnSnS4 (CZTS) is a promising material for thin film solar cells or solar water splitting cells. Generally, large grain size and vertical penetration are highly desirable microstructures to high-efficiency solar conversion devices. Up to date, some kinds of vacuum methods have been used to prepare large grain-sized CZTS, which are expensive and limit their applications on a large scale. It is still a key challenge to prepare large-grained and vertical-penetration CZTS by a low-cost solution method. In this study, we obtained vertical-penetration CZTS thin film with 1.3 MUm grain sizes by a faclie solution method. Different from previous studies, precursor solution was aged in high-humidity air before it was used to prepare CZTS films. The grain size prepared with aging precursor solution was one of the largest among the samples prepared by a solution method after sulfurizing. Moreover, the large-grained CZTS films were used as photocathodes for solar water splitting, which exhibited a much higher photocurrent than those of the samples without aging. To the best of our knowledge, this is the first demonstration to promote grain growth in CZTS by aging precursor solution in high-humidity air. This aging method can offer a reference to prepare other high-performance films. PMID- 26863182 TI - Asymmetric Walkway: A Novel Behavioral Assay for Studying Asymmetric Locomotion. AB - Behavioral assays are commonly used for the assessment of sensorimotor impairment in the central nervous system (CNS). The most sophisticated methods for quantifying locomotor deficits in rodents is to measure minute disturbances of unconstrained gait overground (e.g., manual BBB score or automated CatWalk). However, cortical inputs are not required for the generation of basic locomotion produced by the spinal central pattern generator (CPG). Thus, unconstrained walking tasks test locomotor deficits due to motor cortical impairment only indirectly. In this study, we propose a novel, precise foot-placement locomotor task that evaluates cortical inputs to the spinal CPG. An instrumented peg-way was used to impose symmetrical and asymmetrical locomotor tasks mimicking lateralized movement deficits. We demonstrate that shifts from equidistant inter stride lengths of 20% produce changes in the forelimb stance phase characteristics during locomotion with preferred stride length. Furthermore, we propose that the asymmetric walkway allows for measurements of behavioral outcomes produced by cortical control signals. These measures are relevant for the assessment of impairment after cortical damage. PMID- 26863183 TI - Motion Control of Urea-Powered Biocompatible Hollow Microcapsules. AB - The quest for biocompatible microswimmers powered by compatible fuel and with full motion control over their self-propulsion is a long-standing challenge in the field of active matter and microrobotics. Here, we present an active hybrid microcapsule motor based on Janus hollow mesoporous silica microparticles powered by the biocatalytic decomposition of urea at physiological concentrations. The directional self-propelled motion lasts longer than 10 min with an average velocity of up to 5 body lengths per second. Additionally, we control the velocity of the micromotor by chemically inhibiting and reactivating the enzymatic activity of urease. The incorporation of magnetic material within the Janus structure provides remote magnetic control on the movement direction. Furthermore, the mesoporous/hollow structure can load both small molecules and larger particles up to hundreds of nanometers, making the hybrid micromotor an active and controllable drug delivery microsystem. PMID- 26863184 TI - Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic. AB - BACKGROUND: In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. OBJECTIVES: To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. METHODS: We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. RESULTS: Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. CONCLUSION: BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality. PMID- 26863185 TI - Synthesis of Quinoxaline Derivatives via Tandem Oxidative Azidation/Cyclization Reaction of N-Arylenamines. AB - A new method was developed for the synthesis of quinoxalines. This method employs N-arylenamines and TMSN3 as the starting materials and implements two oxidative C N bond-forming processes in a tandem pattern by using (diacetoxyiodo)benzene as the common oxidant. The present reaction conditions are mild and simple and thus are useful in practical synthesis. PMID- 26863186 TI - A receptor heteromer mediates the male perception of female attractants in plants. AB - Sexual reproduction requires recognition between the male and female gametes. In flowering plants, the immobile sperms are delivered to the ovule-enclosed female gametophyte by guided pollen tube growth. Although the female gametophyte secreted peptides have been identified to be the chemotactic attractant to the pollen tube, the male receptor(s) is still unknown. Here we identify a cell surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives female attractant LURE1 in Arabidopsis thaliana. MDIS1, MIK1 and MIK2 are plasma membrane-localized receptor-like kinases with extracellular leucine-rich repeats and an intracellular kinase domain. LURE1 specifically binds the extracellular domains of MDIS1, MIK1 and MIK2, whereas mdis1 and mik1 mik2 mutant pollen tubes respond less sensitively to LURE1. Furthermore, LURE1 triggers dimerization of the receptors and activates the kinase activity of MIK1. Importantly, transformation of AtMDIS1 to the sister species Capsella rubella can partially break down the reproductive isolation barrier. Our findings reveal a new mechanism of the male perception of the female attracting signals. PMID- 26863187 TI - Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. AB - Mammalian Wnt proteins are believed to act as short-range signals, yet have not been previously visualized in vivo. Self-renewal, proliferation and differentiation are coordinated along a putative Wnt gradient in the intestinal crypt. Wnt3 is produced specifically by Paneth cells. Here we have generated an epitope-tagged, functional Wnt3 knock-in allele. Wnt3 covers basolateral membranes of neighbouring stem cells. In intestinal organoids, Wnt3-transfer involves direct contact between Paneth cells and stem cells. Plasma membrane localization requires surface expression of Frizzled receptors, which in turn is regulated by the transmembrane E3 ligases Rnf43/Znrf3 and their antagonists Lgr4 5/R-spondin. By manipulating Wnt3 secretion and by arresting stem-cell proliferation, we demonstrate that Wnt3 mainly travels away from its source in a cell-bound manner through cell division, and not through diffusion. We conclude that stem-cell membranes constitute a reservoir for Wnt proteins, while Frizzled receptor turnover and 'plasma membrane dilution' through cell division shape the epithelial Wnt3 gradient. PMID- 26863188 TI - A pentanuclear iron catalyst designed for water oxidation. AB - Although the oxidation of water is efficiently catalysed by the oxygen-evolving complex in photosystem II (refs 1 and 2), it remains one of the main bottlenecks when aiming for synthetic chemical fuel production powered by sunlight or electricity. Consequently, the development of active and stable water oxidation catalysts is crucial, with heterogeneous systems considered more suitable for practical use and their homogeneous counterparts more suitable for targeted, molecular-level design guided by mechanistic understanding. Research into the mechanism of water oxidation has resulted in a range of synthetic molecular catalysts, yet there remains much interest in systems that use abundant, inexpensive and environmentally benign metals such as iron (the most abundant transition metal in the Earth's crust and found in natural and synthetic oxidation catalysts). Water oxidation catalysts based on mononuclear iron complexes have been explored, but they often deactivate rapidly and exhibit relatively low activities. Here we report a pentanuclear iron complex that efficiently and robustly catalyses water oxidation with a turnover frequency of 1,900 per second, which is about three orders of magnitude larger than that of other iron-based catalysts. Electrochemical analysis confirms the redox flexibility of the system, characterized by six different oxidation states between Fe(II)5 and Fe(III)5; the Fe(III)5 state is active for oxidizing water. Quantum chemistry calculations indicate that the presence of adjacent active sites facilitates O-O bond formation with a reaction barrier of less than ten kilocalories per mole. Although the need for a high overpotential and the inability to operate in water-rich solutions limit the practicality of the present system, our findings clearly indicate that efficient water oxidation catalysts based on iron complexes can be created by ensuring that the system has redox flexibility and contains adjacent water-activation sites. PMID- 26863189 TI - Structural basis for promiscuous PAM recognition in type I-E Cascade from E. coli. AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) and the cas (CRISPR-associated) operon form an RNA-based adaptive immune system against foreign genetic elements in prokaryotes. Type I accounts for 95% of CRISPR systems, and has been used to control gene expression and cell fate. During CRISPR RNA (crRNA)-guided interference, Cascade (CRISPR-associated complex for antiviral defence) facilitates the crRNA-guided invasion of double-stranded DNA for complementary base-pairing with the target DNA strand while displacing the non-target strand, forming an R-loop. Cas3, which has nuclease and helicase activities, is subsequently recruited to degrade two DNA strands. A protospacer adjacent motif (PAM) sequence flanking target DNA is crucial for self versus foreign discrimination. Here we present the 2.45 A crystal structure of Escherichia coli Cascade bound to a foreign double-stranded DNA target. The 5' ATG PAM is recognized in duplex form, from the minor groove side, by three structural features in the Cascade Cse1 subunit. The promiscuity inherent to minor groove DNA recognition rationalizes the observation that a single Cascade complex can respond to several distinct PAM sequences. Optimal PAM recognition coincides with wedge insertion, initiating directional target DNA strand unwinding to allow segmented base-pairing with crRNA. The non-target strand is guided along a parallel path 25 A apart, and the R-loop structure is further stabilized by locking this strand behind the Cse2 dimer. These observations provide the structural basis for understanding the PAM-dependent directional R loop formation process. PMID- 26863190 TI - Moralistic gods, supernatural punishment and the expansion of human sociality. AB - Since the origins of agriculture, the scale of human cooperation and societal complexity has dramatically expanded. This fact challenges standard evolutionary explanations of prosociality because well-studied mechanisms of cooperation based on genetic relatedness, reciprocity and partner choice falter as people increasingly engage in fleeting transactions with genetically unrelated strangers in large anonymous groups. To explain this rapid expansion of prosociality, researchers have proposed several mechanisms. Here we focus on one key hypothesis: cognitive representations of gods as increasingly knowledgeable and punitive, and who sanction violators of interpersonal social norms, foster and sustain the expansion of cooperation, trust and fairness towards co-religionist strangers. We tested this hypothesis using extensive ethnographic interviews and two behavioural games designed to measure impartial rule-following among people (n = 591, observations = 35,400) from eight diverse communities from around the world: (1) inland Tanna, Vanuatu; (2) coastal Tanna, Vanuatu; (3) Yasawa, Fiji; (4) Lovu, Fiji; (5) Pesqueiro, Brazil; (6) Pointe aux Piments, Mauritius; (7) the Tyva Republic (Siberia), Russia; and (8) Hadzaland, Tanzania. Participants reported adherence to a wide array of world religious traditions including Christianity, Hinduism and Buddhism, as well as notably diverse local traditions, including animism and ancestor worship. Holding a range of relevant variables constant, the higher participants rated their moralistic gods as punitive and knowledgeable about human thoughts and actions, the more coins they allocated to geographically distant co-religionist strangers relative to both themselves and local co-religionists. Our results support the hypothesis that beliefs in moralistic, punitive and knowing gods increase impartial behaviour towards distant co-religionists, and therefore can contribute to the expansion of prosociality. PMID- 26863191 TI - Regeneration: Stem cells make the bowel nervous. PMID- 26863192 TI - Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid. AB - In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue. How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical. Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen availability and tissue damage. PMID- 26863194 TI - Anthropology: Hand of the gods in human civilization. PMID- 26863193 TI - Plankton networks driving carbon export in the oligotrophic ocean. AB - The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterized. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria and alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of a few bacterial and viral genes can predict a significant fraction of the variability in carbon export in these regions. PMID- 26863195 TI - Polygenic evolution of a sugar specialization trade-off in yeast. AB - The evolution of novel traits can involve many mutations scattered throughout the genome. Detecting and validating such a suite of alleles, particularly if they arose long ago, remains a key challenge in evolutionary genetics. Here we dissect an evolutionary trade-off of unprecedented genetic complexity between long diverged species. When cultured in 1% glucose medium supplemented with galactose, Saccharomyces cerevisiae, but not S. bayanus or other Saccharomyces species, delayed commitment to galactose metabolism until glucose was exhausted. Promoters of seven galactose (GAL) metabolic genes from S. cerevisiae, when introduced together into S. bayanus, largely recapitulated the delay phenotype in 1% glucose galactose medium, and most had partial effects when tested in isolation. Variation in GAL coding regions also contributed to the delay when tested individually in 1% glucose-galactose medium. When combined, S. cerevisiae GAL coding regions gave rise to profound growth defects in the S. bayanus background. In medium containing 2.5% glucose supplemented with galactose, wild-type S. cerevisiae repressed GAL gene expression and had a robust growth advantage relative to S. bayanus; transgenesis of S. cerevisiae GAL promoter alleles or GAL coding regions was sufficient for partial reconstruction of these phenotypes. S. cerevisiae GAL genes thus encode a regulatory program of slow induction and avid repression, and a fitness detriment during the glucose-galactose transition but a benefit when glucose is in excess. Together, these results make clear that genetic mapping of complex phenotypes is within reach, even in deeply diverged species. PMID- 26863196 TI - The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. AB - Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N(6)-methyladenosine (m(6)A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N(1)-methyladenosine (m(1)A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m(1)A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA. PMID- 26863197 TI - Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. AB - The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord. The ENS has been called the 'second brain' given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR. PMID- 26863198 TI - Analysis of public oral toxicity data from REACH registrations 2008-2014. AB - The European Chemicals Agency, ECHA, made available a total of 13,832 oral toxicity studies for 8,568 substances up to December 2014. 75% of studies were from the retired OECD Test Guideline 401 (11% TG 420, 11% TG 423 and 1.5% TG 425). Concordance across guidelines, evaluated by comparing LD50 values >= 2000 or < 2000 mg/kg body weight from chemicals tested multiple times between different guidelines, was at least 75% and for their own repetition more than 90%. In 2009, Bulgheroni et al. created a simple model for predicting acute oral toxicity using no observed adverse effect levels (NOAEL) from 28-day repeated dose toxicity studies in rats. This was reproduced here for 1,625 substances. In 2014, Taylor et al. suggested no added value of the 90-day repeated dose oral toxicity test given the availability of a low 28-day study with some constraints. We confirm that the 28-day NOAEL is predictive (albeit imperfectly) of 90-day NOAELs, however, the suggested constraints did not affect predictivity. 1,059 substances with acute oral toxicity data (268 positives, 791 negatives, all Klimisch score 1) were used for modeling: The Chemical Development Kit was used to generate 27 molecular descriptors and a similarity-informed multilayer perceptron showing 71% sensitivity and 72% specificity. Additionally, the k nearest neighbors (KNN) algorithm indicated that similarity-based approaches alone may be poor predictors of acute oral toxicity, but can be used to inform the multilayer perceptron model, where this was the feature with highest information value. PMID- 26863199 TI - What Makes Oxidized N-Acylanthranilamides Stable? AB - Oligoamides composed of anthranilic acid derivatives present a promising choice for mediating long-range charge transfer and controlling its directionality. Hole hopping, modulated by the anthranilamide (Aa) permanent dipoles, provides a plausible means for such rectified long-range charge transduction. All aliphatic and most aromatic amides, however, decompose upon oxidation, rendering them unacceptable for hole-hopping pathways. We, therefore, employ electrochemical and computational analysis to examine how to suppress oxidative degradation and stabilize the radical cations of N-acylated Aa derivatives. Our findings reveal two requirements for attaining long-lived radical cations of these aromatic amides: (1) keeping the reduction potentials for oxidizing the Aa residues under about 1.4 V vs SCE and (2) adding an electron-donating group para to the N terminal amide of the aromatic ring, which prevents the electron spin density of the radical cation from extending over the C-terminal amide. These findings provide essential information for the design of hole-transfer amides. PMID- 26863200 TI - Hydrosulfide Adducts of Organo-Iridium Anticancer Complexes. AB - Novel half-sandwich hydrosulfidoiridium(III) complexes [(eta(5) Cp*)Ir(phen)(SH)]PF6 (1), [(eta(5)-Cp*)Ir(bpy)(SH)]PF6 (2), [(eta(5) Cp(biph))Ir(phen)(SH)]PF6 (3), and [(eta(5)-Cp(biph))Ir(bpy)(SH)]PF6 (4) were prepared from the chlorido complexes by dechlorination and treatment with excess NaSH.xH2O; phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, Cp* = 1,2,3,4,5 pentamethylcyclopentadienyl, and Cp(biph) = 1,2,3,4-tetramethyl-5 biphenylcyclopentadienyl. Complexes 1-4 were characterized by various techniques including electrospray ionization mass spectrometry, NMR spectroscopy (delta(SH) ca. -2 ppm), and a single-crystal X-ray analysis. Complex [(eta(5) Cp*)Ir(phen)(SH)]BPh4 (1') shows a typical piano-stool geometry with Ir-S bond length of 2.388(2) A. Cp(biph) complexes 3 (IC50 = 0.98 MUM) and 4 (IC50 = 0.61 MUM) showed significantly higher (p < 0.005) in vitro antiproliferative activity against A2780 human ovarian cancer cells, as compared with their Cp* analogues 1 (IC50 = 49.5 MUM) and 2 (IC50 = 48.4 MUM), and potency similar to the anticancer drug cisplatin. The complexes were relatively stable in aqueous solution toward hydrolysis and reactions with reduced glutathione (GSH), 9-ethylguanine, or 9 methyladenine. Interestingly, GSH was readily oxidized to glutathione disulfide in the presence of Cp(biph) complexes 3 and 4, as judged by (1)H NMR, perhaps indicative of a possible redox-linked mechanism of action. PMID- 26863201 TI - Encoded Hydrogel Microparticles for Sensitive and Multiplex microRNA Detection Directly from Raw Cell Lysates. AB - In recent years, microRNAs (miRNAs) have emerged as promising diagnostic markers because of their unique dysregulation patterns under various disease conditions and high stability in biological fluids. However, current methods of analyzing miRNA levels typically require RNA isolation, which is cumbersome and time consuming. To achieve high-throughput and accurate miRNA profiling, this study eliminates the need for purification steps by detecting miRNA directly from raw cellular lysate using nonfouling polyethylene glycol microparticles. In contrast to recent studies on direct miRNA measurements from cell lysate, our hydrogel based system provides high-confidence quantification with robust performance. The lysis buffer for the assay was optimized to maximize reaction and labeling efficiency, and this assay has a low limit of detection (<1000 cells) without target amplification. Additionally, the capability for multiplexing was demonstrated through analyzing the levels of three endogenous miRNAs in 3T3 cell lysate. This versatile platform holds great potential for rapid and reliable direct miRNA quantification in complex media, and can be further extended to single-cell analysis by exploiting the flexibility and scalability of our system. PMID- 26863202 TI - Three-Dimensional Versus Two-Dimensional Laparoscopic Right Hemicolectomy. AB - BACKGROUND AND AIMS: To address the issue whether three dimensional (3D) offers real operative time advantages to the surgical procedure (primary endpoint) and significant reduction of surgeon's physical strain (secondary endpoint), we have retrospectively analyzed two consecutive series of laparoscopic right hemicolectomy (LRH) performed by a single experienced laparoscopic colorectal surgeon with two different imaging systems (two dimensional [2D] and 3D). PATIENTS AND METHODS: Since January 2014, 25 consecutive patients with right colon cancer underwent 3D LRH and other 25 consecutive ones received a 2D LRH by a single experienced surgeon. After the insertion of the access ports, the surgical procedure has been divided in component tasks and the execution times were compared. Upon completion of each procedure, the consultant surgeon was asked to complete a nonvalidated subjective questionnaire to evaluate quality of depth perception and surgical strain. RESULTS: The execution times for the entire procedure and the single tasks were not significantly different between the 2D and 3D groups, except for the second task "side-to-side ileotransverse anastomosis" (P < .05). The surgeon experienced better depth perception with the 3D system and subjectively reported less strain using the 3D vision system rather than the 2D system, particularly during longer procedures. CONCLUSIONS: Three dimensional imaging seems not to influence the performance time of laparoscopic right colon cancer surgery when the surgeon is experienced in 2D laparoscopy, although the 3D system seems to offer better depth perception and to subjectively determine less physical strain compared to 2D vision. Further comparative studies are necessary to address the issue whether novice surgeons could benefit from a reduced learning curve using 3D vision and to verify with greater numbers if 3D, even with a similar operative time, can reduce perioperative complications. PMID- 26863203 TI - Partnering to advance early detection and prevention efforts for pancreatic cancer: the Florida Pancreas Collaborative. PMID- 26863204 TI - Self-Sustained Oscillatory Sliding Movement of Doublet Microtubules and Flagellar Bend Formation. AB - It is well established that the basis for flagellar and ciliary movements is ATP dependent sliding between adjacent doublet microtubules. However, the mechanism for converting microtubule sliding into flagellar and ciliary movements has long remained unresolved. The author has developed new sperm models that use bull spermatozoa divested of their plasma membrane and midpiece mitochondrial sheath by Triton X-100 and dithiothreitol. These models enable the observation of both the oscillatory sliding movement of activated doublet microtubules and flagellar bend formation in the presence of ATP. A long fiber of doublet microtubules extruded by synchronous sliding of the sperm flagella and a short fiber of doublet microtubules extruded by metachronal sliding exhibited spontaneous oscillatory movements and constructed a one beat cycle of flagellar bending by alternately actuating. The small sliding displacement generated by metachronal sliding formed helical bends, whereas the large displacement by synchronous sliding formed planar bends. Therefore, the resultant waveform is a half-funnel shape, which is similar to ciliary movements. PMID- 26863205 TI - Movement Patterns and Residency of the Critically Endangered Horseshoe Crab Tachypleus tridentatus in a Semi-Enclosed Bay Determined Using Acoustic Telemetry. AB - The horseshoe crab Tachypleus tridentatus is critically endangered in Japan due to rapidly decreasing numbers resulting from the loss of tidal flats and sandy beaches, and the deterioration of coastal environments. We monitored the year round migratory patterns and residency of this species in a coastal embayment at Tsuyazaki, Japan, using acoustic telemetry. Total 20 adult crabs (15 males and 5 females) were tagged with ultrasonic transmitters and tracked during two periods (2006-2008; n = 10 and 2007-2009; n = 10). Adult crabs were more active during periods of higher water temperatures and their activity peaked in July, during the spawning period. Water temperature appeared to be one of the key factors influencing the movement patterns for the species. Moreover, the crabs tended to be more active at night than in the day. The nocturnal activity pattern was clearly evident before and during the reproductive period (May-August). Tracking data also showed that one pair-bond was maintained for a maximum of 17 days after the pair-bonded female had spawned. Overall, 11 males (73% of 15 individuals) remained in the bay area over winter, whereas three females (60% of 5 individuals) overwintered outside of the bay. Telemetry data showed that over 60% (13 of 20) of tagged crabs overwintered within the bay where there are sandy beaches, mudflats, and scattered seagrass beds. This year-round residence by adult T. tridentatus in the bay area identifies it as a critical habitat for the management of this species, regardless of life-stage. Not only is it a comprehensive management strategy that effectively reflects this species' habitat use patterns but also its implementation, such as the establishment of a protected area, would contribute to its conservation. PMID- 26863206 TI - Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish. AB - Peripheral glia are known to have a critical role in the initial response to axon damage and degeneration. However, little is known about the cellular responses of non-myelinating glia to nerve injury. In this study, we analyzed the transcriptomes of wild-type and mutant (lacking peripheral glia) zebrafish larvae that were treated with metronidazole. This treatment allowed us to conditionally and selectively ablate cranial sensory neurons whose axons are ensheathed only by non-myelinating glia. While transcripts representing over 27,000 genes were detected by RNAseq, only a small fraction (~1% of genes) were found to be differentially expressed in response to neuronal degeneration in either line at either 2 hrs or 5 hrs of metronidazole treatment. Analysis revealed that most expression changes (332 out of the total of 458 differentially expressed genes) occurred over a continuous period (from 2 to 5 hrs of metronidazole exposure), with a small number of genes showing changes limited to only the 2 hr (55 genes) or 5 hr (71 genes) time points. For genes with continuous alterations in expression, some of the most meaningful sets of enriched categories in the wild type line were those involving the inflammatory TNF-alpha and IL6 signaling pathways, oxidoreductase activities and response to stress. Intriguingly, these changes were not observed in the mutant line. Indeed, cluster analysis indicated that the effects of metronidazole treatment on gene expression was heavily influenced by the presence or absence of glia, indicating that the peripheral non myelinating glia play a significant role in the transcriptional response to sensory neuron degeneration. This is the first transcriptome study of metronidazole-induced neuronal death in zebrafish and the response of non myelinating glia to sensory neuron degeneration. We believe this study provides important insight into the mechanisms by which non-myelinating glia react to neuronal death and degeneration in sensory circuits. PMID- 26863207 TI - Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex. AB - Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID- 26863208 TI - Ultrasonic Elastography Research Based on a Multicenter Study: Adding Strain Ratio after 5-Point Scoring Evaluation or Not. AB - BACKGROUND: This study aimed to confirm whether strain ratio should be added after evaluation of lesions with 5-point elasticity scoring for differentiating benign and malignant breast lesions on ultrasonographic elastography(UE). MATERIALS AND METHODS: From June 2010 to March 2012, 1080 consecutive female patients with breast lesions were recruited into a multicenter retrospective study, which involved 8 centers across China. Each institutional ethic review board approved the study, and all the patients gave written informed consent. All the patients underwent the UE procedure and the strain ratios were calculated and the final diagnosis was made by histological findings. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each of the two evaluation systems and the areas under the ROC curve were compared. RESULTS: The strain ratios of benign lesions (mean, 2.6+/-2.0) and malignant lesions (mean,7.9+/-5.8) were significantly different (p <0.01). When the cutoff point was 3.01, strain ratio method had 79.8% sensitivity, 82.8% specificity, and 81.3% accuracy, while the 5-point scoring method had 93.1% sensitivity, 73.0% specificity, and 76.8% accuracy. The areas under the ROC curve with the strain ratio method and 5-point scoring method were 0.863 and 0.865, respectively(p>0.05). The strain ratio method shows better a diagnosis performance of the lesions with elasticity score 3 and 4. CONCLUSIONS: Although the two UE methods have similar diagnostic performance, separate calculation of the strain ratios seems compulsory, especially for the large solid breast lesions and the lesions with elasticity score 3 and 4. PMID- 26863209 TI - Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension. AB - Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID- 26863210 TI - Continuous Collection of Adeno-Associated Virus from Producer Cell Medium Significantly Increases Total Viral Yield. AB - The ability to efficiently produce large amounts of high-titer recombinant adeno associated virus (AAV) is a prerequisite to the continued success of AAV as a gene therapy tool targeted toward large-animal preclinical studies or human clinical therapeutics. Current manufacturing procedures necessitate laborious and time-consuming purification procedures to obtain AAV particles of sufficient titer and purity for these demanding biomedical applications. The finding that AAV can be harvested and purified from producer cell medium may represent an efficient alternative to purifying AAV from cellular lysates. Here we sought to determine the maximum duration of time, and frequency within which AAV can be harvested from producer cell medium, in order to maximize the yield obtained from a single transfection preparation. Human embryonic kidney 293T cells were transfected with polyethylenimine to produce AAV2/5 expressing green fluorescent protein (GFP), and cellular medium was harvested every 2 days until a maximum duration of 19 days posttransfection. AAV2/5-GFP was released into producer cell medium at a steady state until 7 days posttransfection, at which time titers dropped dramatically. Harvesting medium every two days resulted in the maximum yield of AAV from a single preparation, and the cumulative yield of AAV harvested from the producer cell medium was 4-fold higher than the yield obtained from a traditional purification of AAV from cellular lysates. The AAV2/5 harvested from medium within the 7-day collection time-course mediated high levels of transduction in vivo, comparable to AAV2/5 harvested from cellular lysates. AAV purified from cell lysates showed increasing amounts of empty particles at 5 and 7 days posttransfection, whereas AAV purified from cell medium did not show an increase in the amount of empty particles throughout the 7-day time course. Finally, we extended these findings to AAV2/9, demonstrating that a comparable ratio of AAV2/9 particles are also released for up to 7 days posttransfection. PMID- 26863211 TI - Visualization of Content Release from Cell Surface-Attached Single HIV-1 Particles Carrying an Extra-Viral Fluorescent pH-Sensor. AB - HIV-1 fusion leading to productive entry has long been thought to occur at the plasma membrane. However, our previous single virus imaging data imply that, after Env engagement of CD4 and coreceptors at the cell surface, the virus enters into and fuses with intracellular compartments. We were unable to reliably detect viral fusion at the plasma membrane. Here, we implement a novel virus labeling strategy that biases towards detection of virus fusion that occurs in a pH neutral environment-at the plasma membrane or, possibly, in early pH-neutral vesicles. Virus particles are co-labeled with an intra-viral content marker, which is released upon fusion, and an extra-viral pH sensor consisting of ecliptic pHluorin fused to the transmembrane domain of ICAM-1. This sensor fully quenches upon virus trafficking to a mildly acidic compartment, thus precluding subsequent detection of viral content release. As an interesting secondary observation, the incorporation of the pH-sensor revealed that HIV-1 particles occasionally shuttle between neutral and acidic compartments in target cells expressing CD4, suggesting a small fraction of viral particles is recycled to the plasma membrane and re-internalized. By imaging viruses bound to living cells, we found that HIV-1 content release in neutral-pH environment was a rare event (~0.4% particles). Surprisingly, viral content release was not significantly reduced by fusion inhibitors, implying that content release was due to spontaneous formation of viral membrane defects occurring at the cell surface. We did not measure a significant occurrence of HIV-1 fusion at neutral pH above this defect-mediated background loss of content, suggesting that the pH sensor may destabilize the membrane of the HIV-1 pseudovirus and, thus, preclude reliable detection of single virus fusion events at neutral pH. PMID- 26863212 TI - Can Perceptuo-Motor Skills Assessment Outcomes in Young Table Tennis Players (7 11 years) Predict Future Competition Participation and Performance? An Observational Prospective Study. AB - Forecasting future performance in youth table tennis players based on current performance is complex due to, among other things, differences between youth players in growth, development, maturity, context and table tennis experience. Talent development programmes might benefit from an assessment of underlying perceptuo-motor skills for table tennis, which is hypothesized to determine the players' potential concerning the perceptuo-motor domain. The Dutch perceptuo motor skills assessment intends to measure the perceptuo-motor potential for table tennis in youth players by assessing the underlying skills crucial for developing technical and tactical qualities. Untrained perceptuo-motor tasks are used as these are suggested to represent a player's future potential better than specific sport skills themselves as the latter depend on exposure to the sport itself. This study evaluated the value of the perceptuo-motor skills assessment for a talent developmental programme by evaluating its predictive validity for competition participation and performance in 48 young table tennis players (7-11 years). Players were tested on their perceptuo-motor skills once during a regional talent day, and the subsequent competition results were recorded half yearly over a period of 2.5 years. Logistic regression analysis showed that test scores did not predict future competition participation (p >0.05). Yet, the Generalized Estimating Equations analysis, including the test items 'aiming at target', 'throwing a ball', and 'eye-hand coordination' in the best fitting model, revealed that the outcomes of the perceptuo-motor skills assessment were significant predictors for future competition results (R2 = 51%). Since the test age influences the perceptuo-motor skills assessment's outcome, another multivariable model was proposed including test age as a covariate (R2 = 53%). This evaluation demonstrates promising prospects for the perceptuo-motor skills assessment to be included in a talent development programme. Future studies are needed to clarify the predictive value in a larger sample of youth competition players over a longer period in time. PMID- 26863213 TI - Choroidal Changes in Patients with Familial Mediterranean Fever. PMID- 26863214 TI - Predictive Factors for Subjective Improvement in Lumbar Spinal Stenosis Patients with Nonsurgical Treatment: A 3-Year Prospective Cohort Study. AB - OBJECTIVE: To assess the predictive factors for subjective improvement with nonsurgical treatment in consecutive patients with lumbar spinal stenosis (LSS). MATERIALS AND METHODS: Patients with LSS were enrolled from 17 medical centres in Japan. We followed up 274 patients (151 men; mean age, 71 +/- 7.4 years) for 3 years. A multivariable logistic regression model was used to assess the predictive factors for subjective symptom improvement with nonsurgical treatment. RESULTS: In 30% of patients, conservative treatment led to a subjective improvement in the symptoms; in 70% of patients, the symptoms remained unchanged, worsened, or required surgical treatment. The multivariable analysis of predictive factors for subjective improvement with nonsurgical treatment showed that the absence of cauda equina symptoms (only radicular symptoms) had an odds ratio (OR) of 3.31 (95% confidence interval [CI]: 1.50-7.31); absence of degenerative spondylolisthesis/scoliosis had an OR of 2.53 (95% CI: 1.13-5.65); <1-year duration of illness had an OR of 3.81 (95% CI: 1.46-9.98); and hypertension had an OR of 2.09 (95% CI: 0.92-4.78). CONCLUSIONS: The predictive factors for subjective symptom improvement with nonsurgical treatment in LSS patients were the presence of only radicular symptoms, absence of degenerative spondylolisthesis/scoliosis, and an illness duration of <1 year. PMID- 26863215 TI - Severe Hyperinsulinaemic Hypoglycaemia in Beckwith-Wiedemann Syndrome due to Paternal Uniparental Disomy of 11p15.5 Managed with Sirolimus Therapy. AB - BACKGROUND: Almost half of the children with Beckwith-Wiedemann syndrome (BWS) will develop hyperinsulinaemic hypoglycaemia (HH). In the majority of BWS cases, HH will be transient; however, approximately in 5% of them, HH will be severe and often medically-unresponsive. Children with BWS due to paternal uniparental disomy (UPD) of chromosome 11p15 belong to this severe category and have traditionally required near-total pancreatectomy. The use of mTOR inhibitors had not been reported yet in this type of patients. CASE: A 1-month-old female with genetically confirmed BWS due to UPD of chromosome 11p15 was admitted for management of severe HH. Blood glucose concentrations were stabilised with high intravenous dextrose concentration, glucagon and octreotide infusions as she was proven to be diazoxide unresponsive. To avoid a subtotal pancreatectomy, an mTOR inhibitor - sirolimus - was introduced. The dose of sirolimus was optimised progressively and she was able to come off intravenous fluids and glucagon therapy. She has not presented any side effects and her growth is normal after 19 months of therapy. CONCLUSION: This is the first case reported of BWS due to UPD of chromosome 11p15 where sirolimus treatment has been effective in stabilising the blood glucose concentrations and avoiding a near-total pancreatectomy without major side effects detected. PMID- 26863216 TI - Adult Asylum Seekers from the Middle East Including Syria in Central Europe: What Are Their Health Care Problems? AB - BACKGROUND: Forced displacement related to persecution and violent conflict has reached a new peak in recent years. The primary aim of this study is to provide an initial overview of the acute and chronic health care problems of asylum seekers from the Middle East, with special emphasis on asylum seekers from Syria. METHODS: Our retrospective data analysis comprised adult patients presenting to our emergency department between 01.11.2011 and 30.06.2014 with the official resident status of an "asylum seeker" or "refugee" from the Middle East. RESULTS: In total, 880 patients were included in the study. Of these, 625 (71.0%) were male and 255 (29.0%) female. The median age was 34 (range 16-84). 222 (25.2%) of our patients were from Syria. The most common reason for presentation was surgical (381, 43.3%), followed by medical (321, 36.5%) and psychiatric (137, 15.6%). In patients with surgical presentations, trauma-related problems were most common (n = 196, 50.6%). Within the group of patients with medical presentation, acute infectious diseases were most common (n = 141, 43.9%), followed by neurological problems (n = 70, 21.8%) and gastrointestinal problems (n = 47, 14.6%). There were no differences between Syrian and non-Syrian refugees concerning surgical or medical admissions. The most common chronic disorder of unclear significance was chronic gastrointestinal problems (n = 132, 15%), followed by chronic musculoskeletal problems (n = 108, 12.3%) and chronic headaches (n = 78, 8.9%). Patients from Syria were significantly younger and more often suffered from a post-traumatic stress disorder than patients of other nationalities (p<0.0001, and p = 0.05, respectively). CONCLUSION: Overall a remarkable number of our very young group of patients suffered from psychiatric disorders and unspecified somatic symptoms. Asylum seekers should be carefully evaluated when presenting to a medical facility and physicians should be aware of the high incidence of unspecified somatic symptoms in this patient population.In general, there is no major difference between asylum seekers from Syria when compared to other nationalities of asylum seekers from the Middle East. PMID- 26863217 TI - General Anesthesia for Dental Treatment in a Patient With Huntington's Chorea. AB - General dentists may be challenged with treating patients with neurodegenerative brain disorders. The primary goal in general anesthesia for these patients is to provide airway protection and a rapid and safe recovery. This article discusses factors that are of significant concern to the dentist-anesthesiologist team treating patients with Huntington's disease and other neurodegenerative conditions. It includes a case report that describes the treatment of a patient with a neurodegenerative disease characterized by uncontrolled movements and which required general anesthesia. The safety of the used necessary medication is accentuated. PMID- 26863218 TI - Opioid Prescribing in Dentistry: Keys for Safe and Proper Usage. AB - Although dentists typically prescribe opioids for pain control in lower doses and for shorter periods of time than other healthcare providers, they need to be mindful of potential unintended consequences, such as dependency by the patients for whom they are prescribed and diversion of the unused pills to others, including drug dealers and substance abusers. Due to public health issues related to the misuse or abuse of prescription drugs, dentists must be aware of which drugs are most commonly misused or abused; be able to identify individuals who may be at risk for prescription drug abuse; and be prepared to manage patients at risk in the dental setting. They should also be cognizant of alternatives or modified approaches to using opioids--including long-acting anesthetics, NSAIDs, and combining non-opioid drugs with differing mechanisms of action to enhance their ability to control pain due to an additive effect. PMID- 26863219 TI - A Review of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) and Enamel Remineralization. AB - White-spot lesions are the earliest macroscopic evidence of enamel caries. In such a situation, the enamel surface layer stays intact during subsurface demineralization, but without treatment the subsurface loss will continue, and eventually the surface layer will collapse and lead to a cavity formation. By introducing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) at this stage the lesion can be reversed. CPP-ACP is a unique, naturally derived protein based remineralizing technology that is now used globally in chewing gums and topical creams. The aim of this review is to expound on the potential for reversal of demineralization through the use of products such as CPP-ACP, and to provide guidance to clinicians considering remineralization as a viable treatment option. PMID- 26863220 TI - Digital Smile Design Meets the Dento-Facial Analyzer: Optimizing Esthetics While Preserving Tooth Structure. AB - This case of an adult male patient with missing maxillary lateral incisors who was unhappy with his smile focuses on implementation of the digital smile design (DSD) concept. Combined with the use of a dento-facial analyzer, DSD, which employs a series of extraoral photographs, allowed the clinician to preoperatively plan different approaches to the treatment and visualize the outcome of each one, as well as to effectively communicate critical tooth position references to the laboratory technician and the patient. The additive approach used in this case minimized tooth preparation while creating an esthetic smile. PMID- 26863221 TI - Elimination of a "Gummy Smile" With Crown Lengthening and Lip Repositioning. AB - Excessive gingival display is considered unattractive by many patients. A combination of surgical approaches may be required to correct this problem. Clinical crown lengthening involves recontouring crestal bone levels and moving the gingival margin in an apical direction. Lip repositioning reduces gingival display by limiting upper lip movement when smiling. This article describes a case in which a combination of clinical crown lengthening and lip repositioning was used to correct excessive gingival display when smiling. PMID- 26863223 TI - KEPLER Mission: development and overview. AB - The Kepler Mission is a space observatory launched in 2009 by NASA to monitor 170,000 stars over a period of four years to determine the frequency of Earth size and larger planets in and near the habitable zone of Sun-like stars, the size and orbital distributions of these planets, and the types of stars they orbit. Kepler is the tenth in the series of NASA Discovery Program missions that are competitively-selected, PI-directed, medium-cost missions. The Mission concept and various instrument prototypes were developed at the Ames Research Center over a period of 18 years starting in 1983. The development of techniques to do the 10 ppm photometry required for Mission success took years of experimentation, several workshops, and the exploration of many 'blind alleys' before the construction of the flight instrument. Beginning in 1992 at the start of the NASA Discovery Program, the Kepler Mission concept was proposed five times before its acceptance for mission development in 2001. During that period, the concept evolved from a photometer in an L2 orbit that monitored 6000 stars in a 50 sq deg field-of-view (FOV) to one that was in a heliocentric orbit that simultaneously monitored 170,000 stars with a 105 sq deg FOV. Analysis of the data to date has detected over 4600 planetary candidates which include several hundred Earth-size planetary candidates, over a thousand confirmed planets, and Earth-size planets in the habitable zone (HZ). These discoveries provide the information required for estimates of the frequency of planets in our galaxy. The Mission results show that most stars have planets, many of these planets are similar in size to the Earth, and that systems with several planets are common. Although planets in the HZ are common, many are substantially larger than Earth. PMID- 26863222 TI - Combining Amplitude Spectrum Area with Previous Shock Information Using Neural Networks Improves Prediction Performance of Defibrillation Outcome for Subsequent Shocks in Out-Of-Hospital Cardiac Arrest Patients. AB - OBJECTIVE: Quantitative ventricular fibrillation (VF) waveform analysis is a potentially powerful tool to optimize defibrillation. However, whether combining VF features with additional attributes that related to the previous shock could enhance the prediction performance for subsequent shocks is still uncertain. METHODS: A total of 528 defibrillation shocks from 199 patients experienced out of-hospital cardiac arrest were analyzed in this study. VF waveform was quantified using amplitude spectrum area (AMSA) from defibrillator's ECG recordings prior to each shock. Combinations of AMSA with previous shock index (PSI) or/and change of AMSA (DeltaAMSA) between successive shocks were exercised through a training dataset including 255shocks from 99patientswith neural networks. Performance of the combination methods were compared with AMSA based single feature prediction by area under receiver operating characteristic curve(AUC), sensitivity, positive predictive value (PPV), negative predictive value (NPV) and prediction accuracy (PA) through a validation dataset that was consisted of 273 shocks from 100patients. RESULTS: A total of61 (61.0%) patients required subsequent shocks (N = 173) in the validation dataset. Combining AMSA with PSI and DeltaAMSA obtained highest AUC (0.904 vs. 0.819, p<0.001) among different combination approaches for subsequent shocks. Sensitivity (76.5% vs. 35.3%, p<0.001), NPV (90.2% vs. 76.9%, p = 0.007) and PA (86.1% vs. 74.0%, p = 0.005)were greatly improved compared with AMSA based single feature prediction with a threshold of 90% specificity. CONCLUSION: In this retrospective study, combining AMSA with previous shock information using neural networks greatly improves prediction performance of defibrillation outcome for subsequent shocks. PMID- 26863225 TI - Qualities and Inequalities in Online Social Networks through the Lens of the Generalized Friendship Paradox. AB - The friendship paradox is the phenomenon that in social networks, people on average have fewer friends than their friends do. The generalized friendship paradox is an extension to attributes other than the number of friends. The friendship paradox and its generalized version have gathered recent attention due to the information they provide about network structure and local inequalities. In this paper, we propose several measures of nodal qualities which capture different aspects of their activities and influence in online social networks. Using these measures we analyse the prevalence of the generalized friendship paradox over Twitter and we report high levels of prevalence (up to over 90% of nodes). We contend that this prevalence of the friendship paradox and its generalized version arise because of the hierarchical nature of the connections in the network. This hierarchy is nested as opposed to being star-like. We conclude that these paradoxes are collective phenomena not created merely by a minority of well-connected or high-attribute nodes. Moreover, our results show that a large fraction of individuals can experience the generalized friendship paradox even in the absence of a significant correlation between degrees and attributes. PMID- 26863224 TI - The Impact of Ischemia/Reperfusion Injury on Liver Allografts from Deceased after Cardiac Death versus Deceased after Brain Death Donors. AB - BACKGROUND AND AIMS: The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro inflammatory markers ceramides and influences graft leukocyte infiltration. METHODS: Hepatocyte inflammation, as assessed by ceramide expression, was evaluated in DCD (n = 13) and DBD (n = 10) livers. Allograft expression of inflammatory and cell death markers, and allograft leukocyte infiltration were evaluated from a contemporaneous independent cohort of DCD (n = 22) and DBD (n = 13) livers. RESULTS: When examining the differences between transplant stages in each group, C18, C20, C24 ceramides showed significant difference in DBD (p<0.05) and C22 ceramide (p<0.05) were more pronounced for DCD. C18 ceramide is correlated to bilirubin, INR, and creatinine after transplant in DCD. Prior to transplantation, DCD livers have reduced leukocyte infiltration compared to DBD allografts. Following reperfusion, the neutrophil infiltration and platelet deposition was less prevalent in DCD grafts while cell death and recipients levels of serum aspartate aminotransferase (AST) of DCD allografts had significantly increased. CONCLUSION: These data suggest that I/R injury generate necrosis in the absence of a strong inflammatory response in DCD livers with an appreciable effect on early graft function. The long-term consequences of increased inflammation in DBD and increased cell death in DCD allografts are unknown and warrant further investigation. PMID- 26863226 TI - Correction: Mutations of the Calcium Channel Gene cacophony Suppress Seizures in Drosophila. PMID- 26863227 TI - No Evidence of the Ego-Depletion Effect across Task Characteristics and Individual Differences: A Pre-Registered Study. AB - Ego-depletion, a psychological phenomenon in which participants are less able to engage in self-control after prior exertion of self-control, has become widely popular in the scientific community as well as in the media. However, considerable debate exists among researchers as to the nature of the ego depletion effect, and growing evidence suggests the effect may not be as strong or robust as the extant literature suggests. We examined the robustness of the ego-depletion effect and aimed to maximize the likelihood of detecting the effect by using one of the most widely used depletion tasks (video-viewing attention control task) and by considering task characteristics and individual differences that potentially moderate the effect. We also sought to make our research plan transparent by pre-registering our hypotheses, procedure, and planned analyses prior to data collection. Contrary to the ego-depletion hypothesis, participants in the depletion condition did not perform worse than control participants on the subsequent self-control task, even after considering moderator variables. These findings add to a growing body of evidence suggesting ego-depletion is not a reliable phenomenon, though more research is needed that uses large sample sizes, considers moderator variables, and pre-registers prior to data collection. PMID- 26863228 TI - Exacerbating the Tragedy of the Commons: Private Inefficient Outcomes and Peer Effect in Experimental Games with Fishing Communities. AB - Economic Experimental Games have shown that individuals make decisions that deviate down from the suboptimal Nash equilibrium. However, few studies have analyzed the case when deviation is above the Nash equilibrium. Extracting from above the Nash equilibrium is inefficient not only socially but also privately and it would exacerbate the tragedy of the commons. That would be the case of a race to the fish when stocks are becoming depleted or driver behavior on a highly congested road. The objective of this study is to analyze private inefficient extraction behavior in experimental games and to associate the type of player and the type of player group with such inefficient outcomes. To do this, we carried out economic experimental games with local coastal fishermen in Colombia, using a setting where the scarcity of the resource allows for an interior Nash equilibrium and inefficient over-extraction is possible. The state of the resource, the type of player and the composition of the group explain, in part, this inefficient behavior. PMID- 26863230 TI - Correction: First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent. PMID- 26863229 TI - When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis. AB - A striking contrast runs through the last 60 years of biopharmaceutical discovery, research, and development. Huge scientific and technological gains should have increased the quality of academic science and raised industrial R&D efficiency. However, academia faces a "reproducibility crisis"; inflation adjusted industrial R&D costs per novel drug increased nearly 100 fold between 1950 and 2010; and drugs are more likely to fail in clinical development today than in the 1970s. The contrast is explicable only if powerful headwinds reversed the gains and/or if many "gains" have proved illusory. However, discussions of reproducibility and R&D productivity rarely address this point explicitly. The main objectives of the primary research in this paper are: (a) to provide quantitatively and historically plausible explanations of the contrast; and (b) identify factors to which R&D efficiency is sensitive. We present a quantitative decision-theoretic model of the R&D process. The model represents therapeutic candidates (e.g., putative drug targets, molecules in a screening library, etc.) within a "measurement space", with candidates' positions determined by their performance on a variety of assays (e.g., binding affinity, toxicity, in vivo efficacy, etc.) whose results correlate to a greater or lesser degree. We apply decision rules to segment the space, and assess the probability of correct R&D decisions. We find that when searching for rare positives (e.g., candidates that will successfully complete clinical development), changes in the predictive validity of screening and disease models that many people working in drug discovery would regard as small and/or unknowable (i.e., an 0.1 absolute change in correlation coefficient between model output and clinical outcomes in man) can offset large (e.g., 10 fold, even 100 fold) changes in models' brute-force efficiency. We also show how validity and reproducibility correlate across a population of simulated screening and disease models. We hypothesize that screening and disease models with high predictive validity are more likely to yield good answers and good treatments, so tend to render themselves and their diseases academically and commercially redundant. Perhaps there has also been too much enthusiasm for reductionist molecular models which have insufficient predictive validity. Thus we hypothesize that the average predictive validity of the stock of academically and industrially "interesting" screening and disease models has declined over time, with even small falls able to offset large gains in scientific knowledge and brute-force efficiency. The rate of creation of valid screening and disease models may be the major constraint on R&D productivity. PMID- 26863231 TI - An Integrative Approach for Understanding Diversity in the Punctelia rudecta Species Complex (Parmeliaceae, Ascomycota). AB - High levels of cryptic diversity have been documented in lichenized fungi, especially in Parmeliaceae, and integrating various lines of evidence, including coalescent-based species delimitation approaches, help establish more robust species circumscriptions. In this study, we used an integrative taxonomic approach to delimit species in the lichen-forming fungal genus Punctelia (Parmeliaceae), with a particular focus on the cosmopolitan species P. rudecta. Nuclear, mitochondrial ribosomal DNA and protein-coding DNA sequences were analyzed in phylogenetic and coalescence-based frameworks. Additionally, morphological, ecological and geographical features of the sampled specimens were evaluated. Five major strongly supported monophyletic clades were recognized in the genus Punctelia, and each clade could be characterized by distinct patterns in medullary chemistry. Punctelia rudecta as currently circumscribed was shown to be polyphyletic. A variety of empirical species delimitation methods provide evidence for a minimum of four geographically isolated species within the nominal taxon Punctelia rudecta, including a newly described saxicolous species, P. guanchica, and three corticolous species. In order to facilitate reliable sample identification for biodiversity, conservation, and air quality bio-monitoring research, these three species have been epitypified, in addition to the description of a new species. PMID- 26863233 TI - Association of infant and young child feeding practices with under-nutrition: evidence from the Nepal Demographic and Health Survey. AB - BACKGROUND: Childhood undernutrition remains a highly influential risk factor in terms of the global burden of disease. Increasing evidence links infant and young child feeding (IYCF) practices to undernutrition. However, the results are inconsistent, and more country-specific studies are needed. OBJECTIVES: To determine the associations between IYCF practices and nutritional outcomes among children aged 0-23 months using a nationally representative dataset. METHODS: The study used data from the 2011 Nepal Demographic and Health Survey, and the data were analysed for children aged 0-23.9 months who had corresponding data for the outcome variables of interest (n = 890). Multiple linear and logistic regressions were undertaken and adjusted for the complex design of the survey, controlling for child, maternal, household and community characteristics. RESULTS: Of the 890 children included in the study, 83% received age-appropriate breastfeeding but only 48% were breastfed within 1 hour of birth. Exclusive breastfeeding under 6 months of age was associated with a higher weight-for-age Z-score (WAZ) and a lower probability of wasting, but the estimated effects were of borderline significance. A significant negative association was found between continued breastfeeding at 1 year and WAZ and weight-for-height Z-score (WHZ). Timely introduction of complementary feeding in children aged 6-8 months was associated with a higher WAZ [effect size (ES) 0.6, P < 0.01] and higher WHZ (ES 0.6, P < 0.05). Higher dietary diversity index (DDI) was associated with higher height-for age Z-score (ES 0.1, P < 0.05 for each DDI point). Children who achieved minimum meal frequency had a higher WAZ (ES 0.3, P < 0.05). CONCLUSION: This is the first study to relate the wide ranges of IYCF indicators with child nutritional outcomes in Nepal, and it underscores the need to improve age-appropriate complementary feeding practices with a sustained focus on exclusive breastfeeding to reduce undernutrition in infants and young children. PMID- 26863232 TI - Identification and Validation of Reference Genes and Their Impact on Normalized Gene Expression Studies across Cultivated and Wild Cicer Species. AB - Quantitative Real-Time PCR (qPCR) is a preferred and reliable method for accurate quantification of gene expression to understand precise gene functions. A total of 25 candidate reference genes including traditional and new generation reference genes were selected and evaluated in a diverse set of chickpea samples. The samples used in this study included nine chickpea genotypes (Cicer spp.) comprising of cultivated and wild species, six abiotic stress treatments (drought, salinity, high vapor pressure deficit, abscisic acid, cold and heat shock), and five diverse tissues (leaf, root, flower, seedlings and seed). The geNorm, NormFinder and RefFinder algorithms used to identify stably expressed genes in four sample sets revealed stable expression of UCP and G6PD genes across genotypes, while TIP41 and CAC were highly stable under abiotic stress conditions. While PP2A and ABCT genes were ranked as best for different tissues, ABCT, UCP and CAC were most stable across all samples. This study demonstrated the usefulness of new generation reference genes for more accurate qPCR based gene expression quantification in cultivated as well as wild chickpea species. Validation of the best reference genes was carried out by studying their impact on normalization of aquaporin genes PIP1;4 and TIP3;1, in three contrasting chickpea genotypes under high vapor pressure deficit (VPD) treatment. The chickpea TIP3;1 gene got significantly up regulated under high VPD conditions with higher relative expression in the drought susceptible genotype, confirming the suitability of the selected reference genes for expression analysis. This is the first comprehensive study on the stability of the new generation reference genes for qPCR studies in chickpea across species, different tissues and abiotic stresses. PMID- 26863234 TI - Combined whole-body vibration training and l-citrulline supplementation improves pressure wave reflection in obese postmenopausal women. AB - Postmenopausal women have increased wave reflection (augmentation pressure (AP) and index (AIx)) and reduced muscle function that predispose them to cardiac diseases and disability. Our aim was to examine the combined and independent effects of whole-body vibration training (WBVT) and l-citrulline supplementation on aortic hemodynamics and plasma nitric oxide metabolites (NOx) in postmenopausal women. Forty-one obese postmenopausal women were randomized to 3 groups: l-citrulline, WBVT+l-citrulline and WBVT+Placebo for 8 weeks. Brachial and aortic systolic blood pressure, diastolic blood pressure, AP, AIx, AIx adjusted to 75 beats/min (AIx@75), and NOx were measured before and after 8 weeks. All groups similarly decreased (P < 0.05) brachial and aortic pressures as well as AP, and similarly increased (P < 0.05) NOx levels. AIx and AIx@75 decreased (P < 0.01) in the WBVT+l-citrulline and WBVT+Placebo groups, but not in the l-citrulline group. The improvement in AIx@75 (-10.5% +/- 8.8%, P < 0.05) in the WBVT+l-citrulline group was significant compared with the l-citrulline group. l-Citrulline supplementation and WBVT alone and combined decreased blood pressures. The combined intervention reduced AIx@75. This study supports the effectiveness of WBVT+l-citrulline as a potential intervention for prevention of hypertension-related cardiac diseases in obese postmenopausal women. PMID- 26863235 TI - Whole-grain pasta reduces appetite and meal-induced thermogenesis acutely: a pilot study. AB - In epidemiological studies, the intake of foods rich in dietary fiber is associated with a reduced risk of developing overweight and type 2 diabetes. This work aims to identify acute strategies to regulate appetite and improve glucose control by using different pasta meals. Hence, 4 different isocaloric lunch meals, consisting of (i) refined-grain pasta (RG+T), (ii) whole-grain pasta (WG+T), (iii) lemon juice-supplemented refined-grain pasta (LRG+T), and (iv) refined-grain pasta with legumes (RG+L), were administered to 8 healthy participants in a crossover design. On the test days, participants underwent baseline measurements, including appetite sensation, blood sample, and resting energy expenditure (EE), after which the test lunch was served. Subjective appetite was assessed and a blood sample was taken each hour for 240 min, and postprandial EE was measured for 3 h. In repeated-measures analysis of covariance (ANCOVA), postprandial fullness (p = 0.001) increased and hunger (p = 0.038) decreased. WG+T had a lower EE than did both LGR+T (p = 0.02) and RG+L (p < 0.001). Likewise, meal-induced thermogenesis was lower for WG+T compared with RG+L (58 +/- 81 kJ vs 248 +/- 188 kJ; p < 0.05). Plasma glucose (p = 0.001) was lower for RG+T, and triacylglycerols (p = 0.02) increased for LRG+T; however, insulin, C-peptide, and ghrelin were comparable in all other meals. In conclusion, our study indicates that acute consumption of whole-grain pasta may promote fullness and reduce hunger, lowering postprandial thermogenesis, and adding lemon juice to the pasta or legumes does not appear to affect appetite. However, none of pasta meal alterations improved the postprandial metabolic profile. PMID- 26863237 TI - Quote ... unquote. PMID- 26863236 TI - Highly Strained Iron(II) Polypyridines: Exploiting the Quintet Manifold To Extend the Lifetime of MLCT Excited States. AB - Halogen substitution at the 6 and 6" positions of terpyridine (6,6"-Cl2-2,2:6',2" terpyridine = dctpy) is used to produce a room-temperature high-spin iron(II) complex [Fe(dctpy)2](BF4)2. Using UV-vis absorption, spectroelectrochemistry, transient absorption, and TD-DFT calculations, we present evidence that the quintet metal-to-ligand charge-transfer excited state ((5)MLCT) can be accessed via visible light absorption and that the thermalized (5,7)MLCT is long-lived at 16 ps, representing a > 100 fold increase compared to the (1,3)MLCT within species such as [Fe(bpy)3](2+). This result opens a new strategy for extending iron(II) MLCT lifetimes for potential use in photoredox processes. PMID- 26863238 TI - The Fallopian Dilemma: African Bodies, Citizenship and Family Planning. AB - In the recent context of the European Union governmental activity-in particular in this time of crisis-immigration-related issues became of pivotal importance. Social healthcare programmes targeting deprived immigrant populations equate reducing social problems with guiding their conduct towards more responsible, healthier habits and life projects. Building upon a set of debates on governing the body and health under advanced liberalism, this paper, focusing on the Portuguese context and on family planning, suggests ideas towards a new research agenda on immigration and public health, claiming that social care interventions are inherently racialized. The insecurities, threats and overall concerns in a time of global crisis create a state of exception, which justifies the deployment of illiberal practices in order to secure collective well-being. In particular, I am interested in how the dominant discourses of the health and social care sectors influence [1] the ways in which "the right thing to do" is constructed and debated and the material effects of these decisions on immigrants lives; [2] the ongoing strategies, micronegotiations of power and truth between different actors; [3] the fading borders of the subject of medical knowledge, which becomes no longer to govern the body merely according to a medical logic, but rather to seek social well-being. PMID- 26863239 TI - Depression in Racial and Ethnic Minorities: the Impact of Nativity and Discrimination. AB - This research examines factors associated with lifetime major depressive disorder in racial and ethnic minorities residing in the USA, with an emphasis on the impact of nativity, discrimination, and health lifestyle behaviors. The Healthy Migrant Effect and Health Lifestyle Theory were used to inform the design of this project. The use of these frameworks not only provides insightful results but also expands their application in mental health disparities research. Logistic regression models were implemented to examine risk factors associated with lifetime major depressive disorder, comparing immigrants to their American-born counterparts as well as to American-born Whites. Data were derived from the Collaborative Psychiatric Epidemiology Surveys (n = 17,249). Support was found for the hypothesis that certain immigrants, specifically Asian and Afro Caribbean, have lower odds of depression as compared their non-immigrant counterparts. Although, Hispanic immigrants directionally had lower odds of depression, this finding was not statistically significant. Furthermore, engaging in excessive alcohol consumption was associated with higher rates of depression (odds ratio (OR) = 2.09, p < 0.001), and the effect of discrimination on depression was found to be significant, even when controlling for demographics. Of all racial and ethnic groups, foreign-born Afro-Caribbeans had the lowest rate of depression at 7 % followed by foreign-born Asians at 8 %. PMID- 26863240 TI - Differences in the Effects of the Great Recession on Health Outcomes among Minority Working-Age Adults. AB - INTRODUCTION: We examined the effects of the Great Recession (December 2007-June 2009) among vulnerable adults who may be at high risk of poor health and low access to health care. METHODS: Our primary outcomes of interest were self reported health status (fair/poor versus good/very good/excellent), and foregoing needed health care due to cost in the past 12 months. RESULTS: Racial and ethnic minorities, except Asians, experienced higher rates of poor/fair health and higher rates of forgone medical care than did White adults. Hispanic and AIAN adults experienced differential effects of the Great Recession, as compared to White adults. CONCLUSIONS: Understanding how vulnerable populations react in times of economic flux will enable policy makers to identify strategies/policies to lessen the burden experienced by vulnerable adults. PMID- 26863241 TI - HIV-Related Mortality Among Adults (>= 18 years) of Various Hispanic or Latino Subgroups--United States, 2006-2010. AB - Hispanics or Latinos residing in the USA are disproportionately affected by HIV when compared to whites. Health outcomes for Hispanics or Latinos diagnosed with HIV infection may vary by Hispanic or Latino subgroup. We analyzed national mortality data from the National Center for Health Statistics for the years 2006 to 2010 to examine differences in HIV-related mortality among Hispanics or Latinos by sociodemographic factors and by Hispanic or Latino subgroup. After adjusting for age, HIV-related death rates per 100,000 population were highest among Hispanics or Latinos who were male (45.6, 95 % confidence interval [CI], 44.4 to 46.9) compared to female (12.0, 95 % CI 11.4 to 12.6), or resided in the Northeast (75.1, 95 % CI 72.2 to 77.9) compared to other US regions at the time of death. The age-adjusted HIV-related death rate was highest among Puerto Ricans (100.9, 95 % CI 97.0 to 104.8) and lowest among Mexicans (16.9, 95 % CI 16.2 to 17.6). Among all deaths, the proportion of HIV-related deaths was more than four times as high among Puerto Ricans (adjusted prevalence ratio = 4.3, 95 % CI 4.1 to 4.5) compared to Mexicans. To ensure better health outcomes for Hispanics or Latinos living with HIV in the USA, medical care and treatment programs should be adapted to address the needs of various Hispanic or Latino subgroups. PMID- 26863242 TI - Acceptability of a Rinse Screening Test for Diagnosing Head and Neck Squamous Cell Carcinoma Among Black Americans. AB - OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease. We evaluated an easy-to-administer and innovative rinse that assays soluble CD44 and total protein as HNSCC early detection markers. We examined whether the rinse was acceptable and whether the results would promote screening behavior. STUDY DESIGN: This is a prospective observational study. METHODS: Participants (N = 150) from underserved, low-income Black American backgrounds completed assessments of satisfaction, intention to repeat test, and likely screening behavior after receiving results. Descriptive statistics, t tests, and analysis of variance (ANOVA) were conducted. RESULTS: The rinse was highly acceptable to participants and perceived to be acceptable among peers. Participants strongly agreed that they would perform the rinse as prescribed, engage in preventative behaviors if results indicated risk of cancer, and initiate treatment if they had a positive cancer finding. Employed participants slightly disliked the taste of the rinse but were more likely to schedule a follow-up appointment and engage in preventative behaviors based on the results. Those with health-care coverage (including public health insurance) reported that the test was harder to perform than those who were uninsured. CONCLUSION: An easy to-use rinse technique is acceptable and likely to promote screening behavior among Black Americans at risk for HNSCC. Given that many cancer screening modalities are considered unpleasant to undergo, this rinse holds promise for promoting screening behaviors and, thereby, may result in early detection of this potentially fatal disease. LEVEL OF EVIDENCE: IV. PMID- 26863243 TI - Erratum to: Acceptability of a Rinse Screening Test for Diagnosing Head and Neck Squamous Cell Carcinoma Among Black Americans. PMID- 26863244 TI - Racial Differences in Age-Related Variations of Testosterone Levels Among US Males: Potential Implications for Prostate Cancer and Personalized Medication. AB - AIM: The magnitude of the age-related declines in testosterone rather than levels measured at single point in time may be related to the genesis of prostate cancer (PCa). We examined age-related variations of testosterone levels among black and white males, which may provide important insights into racial disparities in PCa incidence and mortality. METHOD: We analyzed data from the 1999-2004 National Health and Nutritional Examination Survey to compare age-related variations in the testosterone levels of 355 black and 631 white males. RESULT: Overall, between the ages of 12 and 15, black males had lower testosterone levels than white males. Testosterone levels increased rapidly with age and reached higher and earlier peak levels in black males compared to white males at 20-30 years of age. After reaching a peak level, testosterone levels declined earlier in blacks than in whites. Further analyses showed that black males had considerably higher levels of testosterone compared to white males aged 20-39 years after adjusting for covariates, including age, body mass index, cigarette smoking, physical activity, and waist circumference; however, no statistically significant differences were observed between the groups at any other age. CONCLUSION: Our study revealed that testosterone levels in black males decrease substantially with increasing age compared to those in white males. This rapid drop in testosterone levels may contribute to racial disparities in PCa. Our findings also suggest that personalized medication for hormone replacement therapy may be necessary to avoid sudden drops in testosterone levels, particularly for black males. PMID- 26863245 TI - Human Papillomavirus Vaccine Knowledge and Attitudes, Preventative Health Behaviors, and Medical Mistrust Among a Racially and Ethnically Diverse Sample of College Women. AB - INTRODUCTION: Medical mistrust is associated with disparities in a variety of health outcomes. The human papillomavirus (HPV) vaccine has the potential to decrease disparities in cervical cancer by preventing infection with the virus that causes these malignancies. No study has examined associations between medical mistrust and preventative health behaviors including the HPV vaccine among young minority women. METHODS: Self-reported racial/ethnic minority students completed a web-based survey in fall of 2011. Wilcoxon and Kruskal Wallis were used to test differences in medical mistrust scores by demographics and health behaviors. RESULTS: Medical mistrust varied significantly by race with Black women reporting the highest scores. Women with no regular health-care provider (HCP) or who had difficulty talking to their provider had higher mistrust. Higher medical mistrust was associated with a preference to receive HPV vaccine recommendation from a HCP of the same race or ethnicity among unvaccinated women. Black and Asian women who had not received the HPV vaccine had higher mistrust scores than vaccinated women. Perceived difficulty in talking to a HCP was associated with ever having a Pap smear. DISCUSSION: Awareness of medical mistrust and the influence on health behaviors may aid in increasing delivery of quality health services for racial and ethnic minority populations. Further research among different populations is needed to elucidate impacts of medical mistrust and provider communication on preventative health behaviors. PMID- 26863246 TI - Racial/Ethnic Minorities Ineligible for Direct Access Colonoscopy (DAC): Identifying Patients Who Fall Through the Cracks. AB - OBJECTIVE: Patients ineligible for direct access colonoscopy (DAC) are typically referred for a pre-colonoscopy consultation with gastroenterology (GI). However, the referral from primary care to GI creates the potential for patients to drop out of treatment. The primary objective of the current study was to examine the proportion of participants deemed ineligible for DAC that (1) attended an appointment with GI and (2) completed a screening colonoscopy. The second aim of the study was to examine predictors of screening colonoscopy adherence. METHODS: Participants (N = 144) were average-risk patients who received a primary care referral for a screening colonoscopy and were deemed ineligible for DAC between 2008 and 2012. Following the primary care visit, participants completed a questionnaire that assessed demographics and psychological factors. Medical chart review determined whether participants completed the screening colonoscopy via the GI referral. RESULTS: Of the 144 participants, only 19 (13 %) completed the screening colonoscopy via the GI referral. Multiple regression analyses revealed that decisional balance was the only unique predictor of screening colonoscopy adherence. CONCLUSIONS: Patients deemed ineligible for DAC are highly unlikely to complete a screening colonoscopy. Interventions are needed to increase screening colonoscopy adherence in this vulnerable population. PMID- 26863247 TI - Black: White Health Disparities in the United States and Chicago: 1990-2010. AB - OBJECTIVES: In order to assess progress in eliminating health disparities, a Healthy People 2010 goal, both at the national level and in Chicago, Illinois, we examined whether disparities between non-Hispanic Black and non-Hispanic White persons widened, narrowed, or stayed the same between 1990 and 2010. METHODS: We examined 17 health status indicators. In order to determine whether a disparity widened, narrowed, or remained unchanged between 1990 and 2010, we examined the relative percentage difference in rates at both time points and at each location. We calculated P values to determine whether changes in relative percentage difference over time were statistically significant. RESULTS: Disparities between non-Hispanic Black and non-Hispanic White populations widened for 8 of the 17 health status indicators examined for the USA (6 significantly), whereas in Chicago the majority of disparities widened (9 of 17, 4 significantly). The mortality gap is responsible for more than 60,000 excess Black deaths per year in the USA. CONCLUSIONS: Despite substantial effort and funds aimed at meeting the Healthy People 2010 goal of eliminating health disparities, minimal progress has been made. PMID- 26863248 TI - Motivation for Psychotherapy and Illness Beliefs in Turkish Immigrant Inpatients in Germany: Results of a Cultural Comparison Study. AB - OBJECTIVE: Some immigrant populations, for instance, Turkish immigrants, suffer from worse mental health than the general population. Moreover, psychotherapeutic treatment does not work well in this group. This might be explained by lower motivation for psychotherapy and particular illness beliefs as important early predictors of treatment outcome. We investigate differences in these predictors between Turkish immigrant inpatients and inpatients without a migration background and evaluate whether particular illness beliefs have a negative impact on motivation for psychotherapy. METHOD: Turkish immigrant inpatients and inpatients without a migration background (N = 100), suffering from depressive disorder, somatoform disorder, and/or adjustment disorder, completed questionnaires assessing motivation for psychotherapy, depressive and somatic symptoms, illness perception, illness-related locus of control, and causal illness attributions. RESULTS: Despite a higher symptom burden, motivation for psychotherapy was lower in Turkish immigrant inpatients than in inpatients without a migration background (d = 0.54). This was fully explained by stronger beliefs in supernatural causes of illness and higher fatalistic-external illness related locus of control in the Turkish immigrant sample (mediation analysis; R (2) = 0.27). CONCLUSIONS: Turkish immigrants believe in supernatural or fatalistic causes of illness and fatalistic-external locus of control to a greater extent than German inpatients without a migration background. These beliefs reduce motivation for psychotherapy and need to be addressed in psychotherapeutic treatment in order to secure positive treatment outcomes. PMID- 26863250 TI - [Icelandic doctors can do much better - to halt unnecessary antimicrobial prescriptions[Editorial]]. PMID- 26863249 TI - The Influence of Race on Overall Survival in Patients with Newly Diagnosed Bladder Cancer. AB - BACKGROUND: Previous studies have reported significant lower incidence yet greater risk of death from bladder cancer (BCa) in African-Americans compared with Caucasians. In this study, the overall survival amongst African-Americans and Caucasians with BCa within the state of Florida is evaluated. MATERIALS AND METHODS: The Florida Cancer Data System and the Florida Agency for Health Care Administration data sets were linked on the basis of unique identifiers, which identified 28,786 patients (27,811 Caucasian and 975 African-Americans) with newly diagnosed BCa from January 1994-December 2009. Data in the database included race/ethnicity, age, smoking history, insurance status, treatment, tumor grade, tumor stage, and overall survival. Chi-square and Mann-Whitney U tests were used to compare variables between African-Americans and Caucasians. Survival rates were calculated by the Kaplan-Meier method while univariate effects were tested by the log-rank test, and multivariate effects were tested by Cox proportional-hazard regression model. P values less than 0.05 were considered statistically significant. RESULTS: Higher clinical stage bladder tumors including T3/4 disease (14.5 % vs. 8.0 %, p < 0.001), lymph node involvement (7.3 % vs. 3.4 %, p < 0.001), and metastatic disease (5.3 % vs. 1.7 %, p < 0.001), as well as higher grade disease (60.2 % vs. 48 %, p < 0.001) were more commonly reported in African-Americans than in Caucasians with newly diagnosed BCa. African-Americans tended to be treated with more aggressive therapies (e.g., radical cystectomy). After adjusting for all covariates, African-Americans actually had more favorable outcomes as related to overall survival (HR = 0.35, 95 % CI, 0.12-0.98, p = 0.045). CONCLUSIONS: Though African-Americans initially present with more aggressive BCa, African-Americans actually have an improved overall survival compared with Caucasians. Though contrary to previous reports, our results may signify a more complex relationship between race and BCa outcomes and thus warrants further attention. PMID- 26863251 TI - [Our biggest challenge ahead[Editorial]]. PMID- 26863252 TI - [Outcomes of acute type A aortic dissection repairs in Iceland]. AB - OBJECTIVES: Acute type A aortic dissection is a life-threatening disease associated with significant morbidity and mortality. Treatment is challenging and requires emergency surgery. This study presents for the first time the short- and long-term outcome of acute type A aortic dissection repairs in Iceland. MATERIALS AND METHODS: A retrospective review of 45 patients (mean age 60.7 +/- 13.9 years, 68.9% male) treated for type A aortic dissection at Landspitali University Hospital between 1992 and 2014. Data was gathered from medical records about known risk factors, presenting symptoms, type of procedure, complications and operative mortality. RESULTS: Out of 45 operations the majority (73.3%) was performed in the second half of the study period. Nearly all patients presented with chest pain and 46.7% were in shock on arrival. Malperfusion syndrome was apparent in 26.7% of cases. A variety of operative methods were used, including hypothermic circulatory arrest in 31.1% of the cases and one-third of patients needed aortic root replacement. Reoperation rate for postoperative bleeding was 29.3% and perioperative stroke occurred in 14.6% of patients. The 30-day mortality rate was 22.2% (10 patients) and 5- and 10-year survival was 71.4 +/- 8.2% and 65.4 +/- 9.4%, respectively. CONCLUSIONS: The short-term outcomes of surgical repair for acute type A aortic dissection in Iceland is comparable to neighbouring countries, including 30-day mortality and long-term survival. Complications, however, are common, especially reoperations for bleeding. 1Department of Cardiothoracic Surgery, Landspitali University Hospital, 2Faculty of Medicine, University of Iceland. KEY WORDS: Aortic dissection type A, aortic aneurysm, open heart surgery, complications, operative mortality, survival. Correspondence: Arnar Geirsson, arnarge@landspitali.is. PMID- 26863253 TI - [Incidence of Bicycle injuries presenting to the Emergency Department in Reykjavik 2005-2010]. AB - INTRODUCTION: Bicycling has become increasingly popular in Iceland. Official registration of bicycle accidents is based on police reports. As minor accidents are often not reported to the police, these accidents may be underreported in police records. The aim of this study was to examine the epidemiology of bicycle related accidents in patients seeking medical assistance at the Emergency Department (ED) at Landspitali-University Hospital, Reykjavik (LUH), Iceland. MATERIALS AND METHODS: This retrospective cohort study was conducted at the ED at LUH, Iceland from January 2005 to December 2010. All medical files were reviewed and sex, age, year and month of accident/injury, helmet wearing, ICD-10 diagnosis, severity of injury according to the Abbreviated Injury Scale (AIS) and the Injury Severity Score (ISS) recorded. The rate of hospital admission was examined with length of stay, Intensive Care Unit admission, use of medical imaging and operative treatment. RESULTS: A total of 3472 patients presented to the ED with bicycle related accidents , 68.3% men and 31.7% female. The average age of patients was 22,6 years (1-95 years). Most are injured during recreational activities (72.4%) and in residence areas (45,7%). Most injuries occurred during May-September (71.4%). Data on counterparty was missing in 74.9% of cases. The cause of accident was in 44.0% a low fall or jump. The upper extremity was injured in 47.1% cases. A majority of the patients (65.6%) had a mild injury (ISS<=3points) and 29.3% had a moderate injury (4-8 points). No fatalities were found during the study period. Use of helmets was only recorded in 14.2% of cases. In total 124 patients were admitted during the period where the mean time of admission was 5 days. CONCLUSION: The incidence of bicycle injuries increased during the study period but appears to have increased less than the number of bicyclists. Injuries are more frequent among males and the majority are of a young age. The accidents usually occur during the spring and summer. Most injuries are minor but 3.6% required admission. Department of Emergency Medicine, The National University Hospital of Iceland1, Icelandic Transportation Safety Board2, Faculty of Medicine, University of Iceland3 KEY WORDS: bicycle accident, emergency department, helmet, injury. Correspondence: Hjalti Mar Bjornsson, hjaltimb@landspitali.is. PMID- 26863254 TI - [The short-and long term effect of multidisciplinary obesity treatment on body mass index and mental health]. AB - INTRODUCTION: The aim of this treatment study was to evaluate both short- and long-term effects of a multidisciplinary obesity treatment. Long-term outcomes of patients receiving gastric bypass surgery in addition to behavioral obesity treatment were compared with those who did not undergo surgery. MATERIAL AND METHODS: The participants were 100 patients undergoing a four week inpatient obesity treatment at the Hospital in Neskaupsstadur (Fjordungsjukrahusid i Neskaupstad (FSN). After treatment was completed, 28 of these patients underwent further treatment, receiving gastric bypass surgery. All patients were followed for two years after completing the four week treatment. Body mass index (BMI), quality of life and symptoms of depression and anxiety were measured for all participants before and after treatment, and again using mailed questionnaires in a cross-sectional data collection in the summer of 2012. RESULTS: Participants achieved statistically significant weight loss (median 1,85 BMI points), improved their quality of life and mental health after four week obesity treatment, and long term results remained significant. Three years after the conclusion of treatment, statistically significant weight loss was still present for patients that had not undergone gastric bypass surgery (median 2.13 BMI points), but improvements in mental health and quality of life were no longer present among subjects who did not undergo surgery. Patients who underwent gastric bypass surgery achieved greater weight loss (median 13.12 BMI points) and longer lasting improvements in mental health and quality of life. CONCLUSION: Results show that the multidisciplinary obesity treatment is effective in reducing obesity and improving mental health and quality of life in the short term. With follow-up treatment, the weight loss is maintained for up to three years after treatment for all participants. The bypass surgery group lost more weight and showed more permanent improvements in mental health and quality of life. These results underline the necessity of providing long-term treatment in maintaining improvements when treating obesity. 1Municipal Service Centre for Midborg and Hlidar 2University of Iceland, 3National University Hospital of Iceland, 4East Coast Regional Hospital in Iceland, 5The Health Care Institution of South Iceland. KEY WORDS: obesity, short- and long term treatment outcomes, weight loss, quality of life, mental health, interdisciplinary treatment. Correspondence: Bjarni Kristinn Gunnarsson bjarnikris@gmail.com. PMID- 26863255 TI - Efficacy of oral Bifidobacterium bifidum ATCC 29521 on microflora and antioxidant in mice. AB - This study aimed to examine whether Bifidobacterium bifidum ATCC 29521, a species of colonic microflora in humans, is involved in the intestinal tract of mice. This study was also conducted to determine the antioxidant activity of this species by evaluating different microbial populations and reactive oxygen species isolated from feces and intestinal contents for 28 days of oral administration. Microbial diversities were assessed through bacterial culture techniques, PCR DGGE, and real-time PCR. This study showed that the intake of B. bifidum ATCC 29521 significantly (p < 0.05) improved the ecosystem of the intestinal tract of BALB/c mice by increasing the amount of probiotics (Lactobacillus intestinalis and Lactobacillus crispatus) and by reducing unwanted bacterial populations (Enterobacter, Escherichia coli). Antioxidative activities of incubated cell-free extracts were evaluated through various assays, including the scavenging ability of DPPH radical (64.5% and 67.54% (p < 0.05), respectively, at 21 days in nutrients and 28 days in MRS broth), superoxide anion, and hydroxyl radical (85% and 61.5% (p < 0.05), respectively, at intestinal contents in nutrients and 21 days in MRS broth). Total reducing power (231.5 MUmol/L (p < 0.05), 14 days in MRS broth) and mRNA level of genes related to oxidative stress were also determined. Results indicated that B. bifidum ATCC 29521 elicits a beneficial effect on murine gut microbiota and antioxidant activities compared with the control samples. This species can be considered as a potential bioresource antioxidant to promote health. Bifidobacterium bifidum ATCC 29521 may also be used as a promising material in microbiological and food applications. PMID- 26863256 TI - Cooling Rate Dependent Ellipsometry Measurements to Determine the Dynamics of Thin Glassy Films. AB - This report aims to fully describe the experimental technique of using ellipsometry for cooling rate dependent Tg (CR-Tg) experiments. These measurements are simple high-throughput characterization experiments, which can determine the glass transition temperature (Tg), average dynamics, fragility and the expansion coefficient of the super-cooled liquid and glassy states for a variety of glassy materials. This technique allows for these parameters to be measured in a single experiment, while other methods must combine a variety of different techniques to investigate all of these properties. Measurements of dynamics close to Tg are particularly challenging. The advantage of cooling rate dependent Tg measurements over other methods which directly probe bulk and surface relaxation dynamics is that they are relatively quick and simple experiments, which do not utilize fluorophores or other complicated experimental techniques. Furthermore, this technique probes the average dynamics of technologically relevant thin films in temperature and relaxation time (taualpha) regimes relevant to the glass transition (taualpha > 100 sec). The limitation to using ellipsometry for cooling rate dependent Tg experiments is that it cannot probe relaxation times relevant to measurements of viscosity (taualpha << 1 sec). Other cooling rate dependent Tg measurement techniques, however, can extend the CR-Tg method to faster relaxation times. Furthermore, this technique can be used for any glassy system so long as the integrity of the film remains throughout the experiment. PMID- 26863257 TI - Does Leveling the Upper Thoracic Spine Have Any Impact on Postoperative Clinical Shoulder Balance in Lenke 1 and 2 Patients? AB - STUDY DESIGN: Retrospective review of prospective data. OBJECTIVE: To determine if surgically leveling the upper thoracic spine in patients with adolescent idiopathic scoliosis results in level shoulders postoperatively. SUMMARY OF BACKGROUND DATA: Research has shown that preoperatively tilted proximal ribs and T1 tilt are more correlated with trapezial prominence than with clavicle angle. METHODS: Prospectively collected Lenke 1 and 2 cases from a single center were reviewed. Clinical shoulder imbalance was measured from 2-year postoperative clinical photos. Lateral shoulder imbalance was assessed utilizing clavicle angle. Medial imbalance was assessed with trapezial angle (TA), and trapezial area ratio (TAR). First rib angle, T1 tilt, and upper thoracic curve were measured from 2-year radiographs. Angular measurements were considered level if <= 3 degrees of zero. TAR was considered level if <= 1 standard deviation of the natural log of the ratio. Upper thoracic Cobb at 2-years was categorized as at or below the mean value (<= 14 degrees ) versus above the mean. RESULTS: Eighty-four patients were identified. There was no significant difference in the percentage of patients with a level clavicle angle or TAR based on first rib being level, T1 tilt being level, or upper thoracic Cobb being at/below versus above the mean (P < 0.05). There was a significant difference in the proportion of patients with level TA based on first rib angle (P = 0.006), T1 tilt (P <= 0.001), and postoperative upper thoracic Cobb (P = 0.04). The odds ratios of having a level TA were 3.9 (1.4-10.6) if first rib was level, 5 (1.9-12.9) if T1 tilt was level, and 2.6 (1.0-6.3) if postoperative upper thoracic Cobb was <= 14 degrees . CONCLUSION: Leveling the upper thoracic spine does not guarantee clinically balanced shoulders or clavicles. Trapezial prominence was impacted by leveling T1 and the first rib and by minimizing the upper thoracic curve. How to achieve laterally balanced shoulders postoperatively remains unclear. LEVEL OF EVIDENCE: 3. PMID- 26863258 TI - Impact of Gender on 30-Day Complications After Adult Spinal Deformity Surgery. AB - STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To determine if postoperative morbidity for patients undergoing spinal deformity surgery varies by sex. SUMMARY OF BACKGROUND DATA: Influence of sex has been investigated in other surgical procedures but has not yet been studied in adult spinal deformity surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative risk factors, intraoperative variables, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. Patients were separated into groups of male and female sex. Univariate analysis and multivariate logistic regression were used to analyze the effect of sex on the incidence of postoperative morbidity and mortality. RESULTS: Female sex was found to be a predictor of any complication[odds ratio (OR): 1.4, 95% confidence interval (CI) 1.2-1.7, P < 0.0001], intra- or postoperative RBC transfusion (OR: 1.6, 95% CI 1.4-1.9, P < .0001), urinary tract infection (OR: 2.0, 95% CI 1.2 3.3, P = 0.0046), and length of stay >5 days (OR: 1.3, 95% CI 1.1-1.5, P = 0.0015). Male sex was associated with higher rate of pulmonary (2.9% vs. 2.0%, P = 0.0344) and cardiac complications (0.9% vs. 0.5%, P = 0.0497). However, male sex as an independent risk factor for pulmonary (OR: 1.4, 95% CI 1.0-2.1, P = 0.0715) and cardiac complications (OR: 1.9, 95% CI 0.9-4.0, P = 0.1076) did not reach significance. CONCLUSION: Female sex was found to increase overall morbidity, particularly for urinary tract infection, transfusion, and length of stay >5 days. Male sex was associated with greater incidence of pulmonary and cardiac complications. Thus, sex and other patient characteristics highlighted must be considered as part of surgical risk planning and patient counseling. LEVEL OF EVIDENCE: 3. PMID- 26863259 TI - Local Epiphyseal Growth Modulation for the Early Treatment of Progressive Scoliosis: Experimental Validation Using a Porcine Model. AB - STUDY DESIGN: Experimental study of a localized device for the control of the vertebral growth using an immature porcine model. OBJECTIVE: The aim of the study was to experimentally evaluate a localized device acting on the epiphyseal growth plates without bridging the intervertebral disc of immature hybrid pigs over 3 months of growth. SUMMARY OF BACKGROUND DATA: Based on current published literature, fusionless devices offer promising scoliosis treatment alternatives to conventional spinal instrumentation and fusion in the growing spine. Current compression-based devices achieve growth modulation while also compressing the intervertebral discs, increasing the risk of long-term disc degeneration. METHODS: An intravertebral staple acting on both the superior and inferior growth plates was inserted locally over T7-T9 of seven healthy immature pigs. Four age matched animals served as controls. Radiographs were acquired monthly to assess induced spinal curvature and vertebral wedging (inverse model). Global (spinal) and local (vertebral, discal) geometric changes were evaluated over 3-months follow-up. Final left/right vertebral height differences were also quantified. RESULTS: The only postoperative complication observed was one pig that had a persistent deep infection and was excluded from the study. No significant changes in spinal alignment were reported in control animals. Final induced Cobb angle was 25.0 degrees +/- 4.2 degrees measured over T7-T9, with no observable sagittal profile modification. Highest vertebral wedging occurred at T9 with 18.2 degrees +/- 2.7 degrees . Cumulative vertebral wedging over T7-T9 accounted for 45.4 degrees , demonstrating evidence of reversed disc wedge phenomenon. Vertebral height was 3.9 +/- 1.0 mm shorter on the instrumented side suggesting full growth restraint. Local and regional induced deformities significantly differed from their control counterparts (P < 0.001). CONCLUSION: In this animal model, the local epiphyseal device achieved significant localized growth modulation over as little as three instrumented levels, with explicit vertebral wedging exclusive of the intervertebral disc. By increasing the number of instrumented levels, one may achieve higher curvature control potentially providing a unique local correction method to correct spinal deformity without affecting the intervertebral disc. LEVEL OF EVIDENCE: 5. PMID- 26863260 TI - Inhibition of p21-Activated Kinase 1 by IPA-3 Promotes Locomotor Recovery After Spinal Cord Injury in Mice. AB - STUDY DESIGN: Ninety-six male adult CD-1 mice were randomly divided into sham, spinal cord injury (SCI) + vehicle, and SCI + IPA-3 groups. Expression of matrix metalloproteinase (MMP)-2 and MMP-9, production of tumor necrosis factors (TNF) alpha and interleukin (IL)-1beta, tissue edema, blood-spinal cord barrier penetrability, neural cell apoptosis, and neurological function recovery were measured. OBJECTIVE: The aim of the study was to evaluate the effect of specific inhibition of p21-activated kinase 1 (PAK1) by IPA-3 on SCI and the underlying mechanisms thereof. SUMMARY OF BACKGROUND DATA: SCI is a devastating clinical condition that may result in long-lasting and deteriorating functional deficits. The major goal of SCI treatment is to limit the development of secondary injury. IPA-3, a PAK1 inhibitor, exhibited neuroprotection against secondary damage after traumatic brain injury and subarachnoid hemorrhage (SAH). METHODS: MMP-2, MMP-9, and cleaved caspase-3 expression were assessed by Western blot. Inflammatory cytokines TNF-alpha and IL-1beta were detected by enzyme-linked immunosorbent assay (ELISA). The blood-spinal cord barrier disruption was measured by water content and Evans blue extravasation of the spinal cord. Neuronal apoptosis was evaluated by Nissl staining and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The locomotor behavior of hind limb was evaluated by Basso Mouse Scale (BMS) at 1, 3, 7, 14, and 28 days post-injury. RESULTS: Compared with SCI + vehicle mice, IPA-3 treatment showed decreased p PAK1, MMP-2, MMP-9, cleaved caspase-3, TNF-alpha, and IL-1beta expression. Moreover, inhibition of PAK1 by IPA-3 reduced spinal cord water content and Evans blue extravasation, increased neuronal survival, and reduced TUNEL-positive cells at 24 hours after SCI. Furthermore, IPA-3 improved spinal cord functional recovery 7 days after SCI. CONCLUSION: Inhibition of PAK1 by IPA-3 promoted recovery of neurological function, possibly by downregulating the expression of MMP-2, MMP-9, TNF-alpha, and IL-1beta. Our data suggest that PAK1 may be a potential therapeutic target in patients with SCI. LEVEL OF EVIDENCE: 1. PMID- 26863261 TI - Predisposing Characteristics of Adjacent Segment Disease After Lumbar Fusion. AB - STUDY DESIGN: Retrospective Review. OBJECTIVE: The aim of this study was to determine medical, radiographic, and surgical risk factors for the development of adjacent segment disease (ASD) after lumbar fusion. SUMMARY OF BACKGROUND DATA: ASD is a recognized outcome of spinal fusion that leads to increased costs and debilitating symptoms for patients. However, a comprehensive understanding of risk factors for the development of this surgical outcome does not exist. METHODS: The medical records of patients who received their first lumbar fusion for any indication were retrospectively examined for preoperative medical comorbidities and medications, as well as surgical approach and perioperative complications. A blinded reviewer assessed radiographs for each patient to examine sagittal alignment after fusion. Multivariable logistic regression was used to model the risk of developing ASD on the basis of one or more predictors. RESULTS: A total of 137 patients fit the inclusion criteria; 9% required a follow up operation for degeneration at segments adjacent to the fusion. The ASD group had a mean follow-up of 21.1 months prior to revision surgery and an overall follow-up of 41.0 months. The average follow-up in the control group was 14.0 months. Statistically significant independent predictors of developing ASD included antidepressant use [odds ratio (OR) = 5.4], diagnosis of degenerative scoliosis (OR = 34.2), fusion of L4-S1 (OR = 56.5), having no decompressions adjacent to the fusion, and low sacral slope (OR = 0.9). No patient who developed ASD received a decompression adjacent to the fusion such that an OR could not be generated for this independent predictor. CONCLUSION: This study is the first to use a combination of medical, surgical, and postoperative sagittal balance as risk factors for the development of adjacent segment disease after lumbar fusion. The awareness of these risk factors may allow for better patient selection and surgical technique to decrease the probability of acquiring this adverse outcome. LEVEL OF EVIDENCE: 4. PMID- 26863262 TI - Inferior Outcome of Lumbar Disc Surgery in Women Due to Inferior Preoperative Status: A Prospective Study in 11,237 Patients. AB - STUDY DESIGN: Analysis of prospectively collected data in a national register. OBJECTIVE: The aim of this study was to, in a nationwide perspective, evaluate whether there exist sex differences in outcome of lumbar disc herniation (LDH) surgery and whether the gender-specific referral pattern influence the outcome. SUMMARY OF BACKGROUND DATA: Previous studies infer that women are referred to LDH surgery with inferior clinical status than men. Whether the surgical outcome is different in men and women is debated. METHODS: We found in the validated Swedish National Spine Surgical Register, 11,237 patients aged 13 to 89 years who between years 2000 and 2010 were registered in SweSpine with LDH surgery and with both preoperative and 1 year postoperative data. The register includes data on sex, age, smoking habits, walking distance, consumption of analgesics, back and leg pain (Visual Analogue Scale; VAS), quality of life (EuroQol; EQ5D and Short Form 36 Questionnaire; SF-36), and disability (Oswestry Disability Index; ODI). We evaluated sex discrepancies in response to surgery and 1 year postoperative outcome. RESULTS: All end point variables improved markedly with a similar rate in both men and women (all P < 0.001). As women preoperatively reported higher consumption of analgesics, more impaired walking distance, more back and leg pain, inferior quality of life and higher disability than men (all P < 0.001) and improvement by surgery was similar in both sex, women reported 1 year after surgery still higher consumption of analgesics, more impaired walking distance, more back and leg pain, inferior quality of life, and higher disability (all P < 0.001). CONCLUSION: Surgery for LDH confers great improvements in both sex. Because women are scheduled for surgery with an inferior clinical status than men and the improvement is similar in both sex, the 1 year postoperative outcome is inferior in women than in men. LEVEL OF EVIDENCE: 2. PMID- 26863263 TI - Chromatin Immunoprecipitation Assay for the Identification of Arabidopsis Protein DNA Interactions In Vivo. AB - Intricate gene regulatory networks orchestrate biological processes and developmental transitions in plants. Selective transcriptional activation and silencing of genes mediate the response of plants to environmental signals and developmental cues. Therefore, insights into the mechanisms that control plant gene expression are essential to gain a deep understanding of how biological processes are regulated in plants. The chromatin immunoprecipitation (ChIP) technique described here is a procedure to identify the DNA-binding sites of proteins in genes or genomic regions of the model species Arabidopsis thaliana. The interactions with DNA of proteins of interest such as transcription factors, chromatin proteins or posttranslationally modified versions of histones can be efficiently analyzed with the ChIP protocol. This method is based on the fixation of protein-DNA interactions in vivo, random fragmentation of chromatin, immunoprecipitation of protein-DNA complexes with specific antibodies, and quantification of the DNA associated with the protein of interest by PCR techniques. The use of this methodology in Arabidopsis has contributed significantly to unveil transcriptional regulatory mechanisms that control a variety of plant biological processes. This approach allowed the identification of the binding sites of the Arabidopsis chromatin protein EBS to regulatory regions of the master gene of flowering FT. The impact of this protein in the accumulation of particular histone marks in the genomic region of FT was also revealed through ChIP analysis. PMID- 26863264 TI - Examination of Proteins Bound to Nascent DNA in Mammalian Cells Using BrdU-ChIP Slot-Western Technique. AB - Histone deacetylases 1 and 2 (HDAC1,2) localize to the sites of DNA replication. In the previous study, using a selective inhibitor and a genetic knockdown system, we showed novel functions for HDAC1,2 in replication fork progression and nascent chromatin maintenance in mammalian cells. Additionally, we used a BrdU ChIP-Slot-Western technique that combines chromatin immunoprecipitation (ChIP) of bromo-deoxyuridine (BrdU)-labeled DNA with slot blot and Western analyses to quantitatively measure proteins or histone modification associated with nascent DNA. Actively dividing cells were treated with HDAC1,2 selective inhibitor or transfected with siRNAs against Hdac1 and Hdac2 and then newly synthesized DNA was labeled with the thymidine analog bromodeoxyuridine (BrdU). The BrdU labeling was done at a time point when there was no significant cell cycle arrest or apoptosis due to the loss of HDAC1,2 functions. Following labeling of cells with BrdU, chromatin immunoprecipitation (ChIP) of histone acetylation marks or the chromatin-remodeler was performed with specific antibodies. BrdU-labeled input DNA and the immunoprecipitated (or ChIPed) DNA was then spotted onto a membrane using the slot blot technique and immobilized using UV. The amount of nascent DNA in each slot was then quantitatively assessed using Western analysis with an anti BrdU antibody. The effect of loss of HDAC1,2 functions on the levels of newly synthesized DNA-associated histone acetylation marks and chromatin remodeler was then determined by normalizing the BrdU-ChIP signal obtained from the treated samples to the control samples. PMID- 26863265 TI - Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. AB - BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.). PMID- 26863266 TI - Association Between Inflammatory Bowel Disease and Erectile Dysfunction: A Nationwide Population-Based Study. AB - BACKGROUND: To determine whether inflammatory bowel disease (IBD) is associated with an increased risk of subsequent erectile dysfunction (ED). METHODS: We identified 1845 patients who received a diagnosis with IBD between 2000 and 2011 from Taiwan's National Health Insurance Research Database. For the comparison cohort, we randomly extracted the data of 7380 patients matched by sex, age, and baseline year. Follow-up continued until the development of ED, withdrawal from the National Health Insurance program, or the end of 2011. The cumulative incidences and hazard ratios (HRs) for ED development were determined. RESULTS: After 12 years of follow-up, subsequent ED incidence rates in the IBD and comparison cohorts were 2.23 and 1.29 per 10,000 person-years, respectively (adjusted hazard ratio = 1.64; 95% confidence interval [CI], 1.07-2.52; P < 0.05). Compared with the non-IBD cohort without comorbidity, the risk of ED was higher in the IBD cohort with comorbidity (adjusted hazard ratio = 2.46, 95% CI, 1.32-4.58). Patients with ulcerative colitis were 2.27-fold more likely to develop ED than were patients without IBD (95% CI, 1.22-4.20). Compared with patients without IBD who were aged <=49 years, patients with IBD aged >=65 years were 3.36-fold more likely to develop ED (95% CI, 1.42-7.96). CONCLUSIONS: We found that the patients with IBD had a 1.64-fold higher risk of developing ED than did the comparison group. Physicians should be aware of the link to ED when assessing patients with IBD. PMID- 26863268 TI - The effect of kinesio tape on neuromuscular activity of peroneus longus. AB - BACKGROUND: Functional ankle instability is the result of sensorimotor or structural deficits. The commonly used kinesio tape (KT) is supposed to have a positive influence on sensorimotor functions. METHODS: Eight women and two men (mean +/- SD, age 24.4 +/- 3.3 years) with functional ankle instability with recurrent ankle sprains ran downhill on a treadmill (3.3 m/s and a negative slope of 5 degrees ). The first trial was without KT, the second with KT on the peroneus longus (PL) muscle. Neuromuscular activity was measured using surface electromyography for 15 seconds. Sensation of giving way was assessed with a visual analog scale (VAS). Comparisons were made between measurements with and without KT using the Wilcoxon rank sum test. The level of significance was set at P <= 0.05. RESULTS: None of the chosen parameters for preactivation, reflex activation, or total activation showed statistically significant differences between the two trials (P > 0.05). The mean values for the sensation of giving way were lower with KT (VAS, median 1.2, range 0-2.8) than without (VAS, median 1.8, range 0-3.9), but did not reach statistical significance (P = 0.102) or clinical relevance. CONCLUSION: KT in participants with functional ankle instability (FAI) seems to have no effect on the neuromuscular activity of PL and sensation of giving way during downhill running. PMID- 26863269 TI - Gold nanoparticles and bioconjugation: a pathway for proteomic applications. AB - In the last few years gold nanoparticles (AuNPs) became extremely interesting materials due to their enhanced optical, chemical and electrical properties. With the intention of taking advantage of those properties, the use of AuNPs has spread into a wide variety of areas such as physics, chemistry, biology, industry and medicine. More interestingly, their ability to form robust conjugates with biomolecules has given proteomics a new tool to improve aspects where the current methods to study proteins and their interactions in living cells cannot achieve the success required. In this review we present some of the current methods for AuNPs synthesis, the tailoring of their surface with ligands to improve stability and strategies to conjugate with biomolecules. Lastly, we also discuss their application in proteomic methods and recent developments in clinical diagnosis. PMID- 26863267 TI - Cytokine Networks and T-Cell Subsets in Inflammatory Bowel Diseases. AB - Pathogenesis of the inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) and Crohn's disease (CD), involve proinflammatory changes within the microbiota, chronic immune-mediated inflammatory responses, and epithelial dysfunction. Converging data from genome-wide association studies, mouse models of IBD, and clinical trials indicate that cytokines are key effectors of both normal homeostasis and chronic inflammation in the gut. Yet many questions remain concerning the role of specific cytokines in different IBDs within distinct regions of the gut, and regarding cellular mechanisms of action. In this article, we review current and emerging concepts concerning the role of cytokines in IBD with a focus on immune regulation, T cell subsets, and potential clinical applications. PMID- 26863270 TI - Quantification of Cerebral Vascular Architecture using Two-photon Microscopy in a Mouse Model of HIV-induced Neuroinflammation. AB - Human Immunodeficiency Virus 1 (HIV-1) infection frequently results in HIV-1 Associated Neurocognitive Disorders (HAND), and is characterized by a chronic neuroinflammatory state within the central nervous system (CNS), thought to be driven principally by virally-mediated activation of microglia and brain resident macrophages. HIV-1 infection is also accompanied by changes in cerebrovascular blood flow (CBF), raising the possibility that HIV-associated chronic neuroinflammation may lead to changes in CBF and/or in cerebral vascular architecture. To address this question, we have used a mouse model for HIV induced neuroinflammation, and we have tested whether long-term exposure to this inflammatory environment may damage brain vasculature and result in rarefaction of capillary networks. In this paper we describe a method to quantify changes in cortical capillary density in a mouse model of neuroinflammatory disease (HIV-1 Tat transgenic mice). This generalizable approach employs in vivo two-photon imaging of cortical capillaries through a thin-skull cortical window, as well as ex vivo two-photon imaging of cortical capillaries in mouse brain sections. These procedures produce images and z-stack files of capillary networks, respectively, which can be then subjected to quantitative analysis in order to assess changes in cerebral vascular architecture. PMID- 26863271 TI - Ultrastructural Changes and Corneal Wound Healing After SMILE and PRK Procedures. AB - PURPOSE: To compare keratocyte activation, cellular morphologic changes and wound healing after SMILE and PRK procedures using transmission electron microscope (TEM). METHODS: In this study, 22 New Zealand white rabbits (10- to 15-week old) were used. The right eyes of all animals underwent SMILE procedure and the left eyes underwent PRK procedure. Cornea samples taken 1 day and 1 week postoperatively were examined using TEM. RESULTS: Using TEM 1 day after SMILE procedure, the organization of collagen fibers seemed to have been preserved without thermal alterations. Keratocyte activation was observed in the anterior stroma. Disrupted collagen arrangement and debris of cells are visible in the area of damage, and some phagocytic cells and a large number of secondary lysosomes are visible in those cells. At the perimeter zone of the interface, many coenocytes and collagen fragments could be found within the phagocytic cell. One week after SMILE procedure, potential lacuna could be discerned. A large part of the interface of the lenticule extracted had an appearance of clearly being adhered to some mucus secretions. One day after PRK procedure, an irregular epithelial surface was visible using TEM. Keratocytes had been activated and the rough endoplasmic reticulum in those cells had expanded. One week after PRK procedure, the epithelial surface still was irregular and keratinization of the epithelium was still visible in some areas. Corneal endothelium cells were mildly damaged and some vacuoles within the cytoplasm could be discerned. In the anterior stroma, some unhealthy activated keratocytes could still be observed. New collagen fibrils were found present near the activated keratocytes. CONCLUSION: Using TEM, keratocyte activation could still be observed after SMILE compared to after PRK procedure. Fewer cellular ultrastructural changes were seen after SMILE procedure. Unlike in PRK procedure, no damaged epithelium and endothelium were found after SMILE. PMID- 26863274 TI - Neuro-rehabilitation Approach for Sudden Sensorineural Hearing Loss. AB - Sudden sensorineural hearing loss (SSHL) is characterized by acute, idiopathic hearing loss. The estimated incidence rate is 5-30 cases per 100,000 people per year. The causes of SSHL and the mechanisms underlying SSHL currently remain unknown. Based on several hypotheses such as a circulatory disturbance to the cochlea, viral infection, and autoimmune disease, pharmaco-therapeutic approaches have been applied to treat SSHL patients; however, the efficacy of the standard treatment, corticosteroid therapy, is still under debate. Exposure to intense sounds has been shown to cause permanent damage to the auditory system; however, exposure to a moderate level enriched acoustic environment after noise trauma may reduce hearing impairments. Several neuroimaging studies recently suggested that the onset of SSHL induced maladaptive cortical reorganization in the human auditory cortex, and that the degree of cortical reorganization in the acute SSHL phase negatively correlated with the recovery rate from hearing loss. This article reports the development of a novel neuro-rehabilitation approach for SSHL, "constraint-induced sound therapy (CIST)". The aim of the CIST protocol is to prevent or reduce maladaptive cortical reorganization by using an enriched acoustic environment. The canal of the intact ear of SSHL patients is plugged in order to motivate them to actively use the affected ear and thereby prevent progress of maladaptive cortical reorganization. The affected ear is also exposed to music via a headphone for 6 hr per day during hospitalization. The CIST protocol appears to be a safe, easy, inexpensive, and effective treatment for SSHL. PMID- 26863275 TI - Reversible metal-induced emission and chromaticity switching in isostructural Ln MOFs. AB - Several new isostructural lanthanide metal-organic frameworks {[Ln3(L)4(OH)(H2O)2].DMAC}n (Ln = Tb (1), Gd (2), Eu (3), Gd0.81Tb0.10Eu0.09 (4) and Gd0.75Tb0.18Eu0.07 (5)) were designed and prepared. Excitingly, samples 1, 3, 4 and 5 showed reversible Al(3+)-induced chromaticity switching as well as reversible Fe(3+)-induced emission switching. PMID- 26863276 TI - Individual finger control of a modular prosthetic limb using high-density electrocorticography in a human subject. AB - OBJECTIVE: We used native sensorimotor representations of fingers in a brain machine interface (BMI) to achieve immediate online control of individual prosthetic fingers. APPROACH: Using high gamma responses recorded with a high density electrocorticography (ECoG) array, we rapidly mapped the functional anatomy of cued finger movements. We used these cortical maps to select ECoG electrodes for a hierarchical linear discriminant analysis classification scheme to predict: (1) if any finger was moving, and, if so, (2) which digit was moving. To account for sensory feedback, we also mapped the spatiotemporal activation elicited by vibrotactile stimulation. Finally, we used this prediction framework to provide immediate online control over individual fingers of the Johns Hopkins University Applied Physics Laboratory modular prosthetic limb. MAIN RESULTS: The balanced classification accuracy for detection of movements during the online control session was 92% (chance: 50%). At the onset of movement, finger classification was 76% (chance: 20%), and 88% (chance: 25%) if the pinky and ring finger movements were coupled. Balanced accuracy of fully flexing the cued finger was 64%, and 77% had we combined pinky and ring commands. Offline decoding yielded a peak finger decoding accuracy of 96.5% (chance: 20%) when using an optimized selection of electrodes. Offline analysis demonstrated significant finger-specific activations throughout sensorimotor cortex. Activations either prior to movement onset or during sensory feedback led to discriminable finger control. SIGNIFICANCE: Our results demonstrate the ability of ECoG-based BMIs to leverage the native functional anatomy of sensorimotor cortical populations to immediately control individual finger movements in real time. PMID- 26863277 TI - Androgen action in female reproductive physiology. AB - PURPOSE OF REVIEW: In the last decade, it has been proven that androgens acting via the androgen receptor (AR) play an important role in the regulation of female reproductive function. However, the specific site of action and the precise pathways involved remain to be fully elucidated. This review aims to combine findings from emerging basic research to provide new insights into the roles of AR-mediated actions, and the mechanisms involved, in normal ovarian, uterine, and mammary gland function. RECENT FINDINGS: Our understanding of the specific roles of androgens in females has been hindered as females with complete androgen insensitivity cannot be generated by natural breeding, and interpretation of results from pharmacological studies has led to confusion as some androgens can be converted into estrogens, which can mediate actions via estrogen receptors. However, with the creation of global and cell-specific female AR knockout mouse models by Cre-LoxP technology, and the use of aromatizable and nonaromatizable androgens, novel roles for androgens in the regulation of female reproductive physiology have been revealed. SUMMARY: AR-mediated mechanisms play important roles in mediating normal ovarian, uterine, and mammary gland function and there is hope that further elucidation of the role of androgens in female reproductive physiology may translate into the development of novel, evidence-based, and targeted treatment for androgen-associated conditions. PMID- 26863278 TI - Triglycerides to high-density lipoprotein-cholesterol ratio, glycemic control and cardiovascular risk in obese patients with type 2 diabetes. AB - PURPOSE OF REVIEW: This article provides an update on the role of the triglyceride to high-density lipoprotein-cholesterol (triglyceride/HDL-C) ratio in the setting of obesity-related insulin resistance and type 2 diabetes mellitus. RECENT FINDINGS: Insulin resistance and type 2 diabetes mellitus are well-established risk factors for cardiovascular diseases, and are commonly associated with metabolic abnormalities such as hypertriglyceridemia, low HDL-C and presence of small, dense low-dense lipoprotein (LDL) particles. Mounting evidence suggests that the triglyceride/HDL-C ratio is a marker of insulin resistance, although this relationship might vary as a function of ethnicity and sex. The triglyceride/HDL-C ratio has also been shown to correlate with other atherogenic lipid measurements, such as triglyceride-rich lipoproteins, remnant cholesterol and small dense LDL particles. Recent epidemiologic studies have shown that the triglyceride/HDL-C ratio associates with cardiovascular risk, mainly because of its association with insulin resistance. Finally, triglyceride/HDL-C can also be a marker of glycemic control, especially in obese patients with type 2 diabetes mellitus. SUMMARY: The triglyceride/HDL-C integrates information on triglyceride-rich lipoproteins, insulin resistance and glycemic control. Future studies may better define its specific clinical role. PMID- 26863279 TI - Editorial: collecting new external evidence for cholesterol management. PMID- 26863280 TI - Facile rhenium-peptide conjugate synthesis using a one-pot derived Re(CO)3 reagent. AB - We have synthesized two Re(CO)3-modified lysine complexes (1 and 2), where the metal is attached to the amino acid at the Nepsilon position, via a one-pot Schiff base formation reaction. These compounds can be used in the solid phase synthesis of peptides, and to date we have produced four conjugate systems incorporating neurotensin, bombesin, leutenizing hormone releasing hormone, and a nuclear localization sequence. We observed uptake into human umbilical vascular endothelial cells as well as differential uptake depending on peptide sequence identity, as characterized by fluorescence and rhenium elemental analysis. PMID- 26863282 TI - Exploring optical mechanotransduction in fluorescent liquid crystal elastomers. AB - Carbazole-based nematic liquid single crystal elastomers switch their fluorescence mechanically on demand enabling a fast optical mechanotransduction under ambient conditions. The identification of the key factors controlling such process is of utmost importance since it might lead to a significant improvement of the transducing abilities of these smart materials. In particular, variations in the length of the fluorophore flexible spacer translates in a distinct mutual interaction between both mesogenic and fluorogenic platforms, giving rise thereby to functional materials with a significantly different mechanofluorescent behaviour. PMID- 26863281 TI - Familial Risk in Patients With Carcinoma of Unknown Primary. AB - IMPORTANCE: Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives. OBJECTIVE: To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of patients who received a diagnosis of CUP between 1980 and 2010 identified from the Utah Cancer Registry. Population controls with no CUP diagnosis were sex and age matched 10:1 to patients with CUP. Data about relatives were drawn from the Utah Population Database. MAIN OUTCOMES AND MEASURES: Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis. RESULTS: For the 4160 index patients (median [interquartile range] age, 72 [62-81] years; 47.6% male) who had received a diagnosis of CUP, first-degree relatives were at an elevated risk of CUP themselves (hazard ratio [HR], 1.35 [95% CI, 1.07-1.70]), as well as lung (HR, 1.37 [95% CI, 1.22-1.54]), pancreatic (HR, 1.28 [95% CI, 1.06-1.54]), myeloma (HR, 1.28 [95% CI, 1.01-1.62]), and non-Hodgkin lymphoma (HR, 1.16 [95% CI, >1.00 1.35]) cancers compared with controls without CUP. When the analysis was restricted to relatives of cancer-free controls, additional increased risks for colon (HR, 1.19 [95% CI, 1.06-1.33]) and bladder (HR, 1.18 [95% CI, >1.00-1.38]) cancers were observed. Second-degree relatives of patients with CUP were at a slight increased risk of lung (HR, 1.14 [95% CI, 1.03-1.26]), pancreatic (HR, 1.17 [95% CI, 1.01-1.37]), breast (HR, 1.09 [95% CI, 1.02-1.16]), melanoma (HR, 1.09 [95% CI, >1.00-1.19]), and ovarian (HR, 1.19 [95% CI, 1.02-1.39]) cancers. CONCLUSIONS AND RELEVANCE: Relatives of patients with CUP are at increased risk of CUP and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for CUP and provide cancer risk information for relatives of patients with CUP that can lead to effective intervention. Relatives of patients with CUP should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening. PMID- 26863283 TI - Fabrication Process of Silicone-based Dielectric Elastomer Actuators. AB - This contribution demonstrates the fabrication process of dielectric elastomer transducers (DETs). DETs are stretchable capacitors consisting of an elastomeric dielectric membrane sandwiched between two compliant electrodes. The large actuation strains of these transducers when used as actuators (over 300% area strain) and their soft and compliant nature has been exploited for a wide range of applications, including electrically tunable optics, haptic feedback devices, wave-energy harvesting, deformable cell-culture devices, compliant grippers, and propulsion of a bio-inspired fish-like airship. In most cases, DETs are made with a commercial proprietary acrylic elastomer and with hand-applied electrodes of carbon powder or carbon grease. This combination leads to non-reproducible and slow actuators exhibiting viscoelastic creep and a short lifetime. We present here a complete process flow for the reproducible fabrication of DETs based on thin elastomeric silicone films, including casting of thin silicone membranes, membrane release and prestretching, patterning of robust compliant electrodes, assembly and testing. The membranes are cast on flexible polyethylene terephthalate (PET) substrates coated with a water-soluble sacrificial layer for ease of release. The electrodes consist of carbon black particles dispersed into a silicone matrix and patterned using a stamping technique, which leads to precisely-defined compliant electrodes that present a high adhesion to the dielectric membrane on which they are applied. PMID- 26863286 TI - Mobile Ion Induced Slow Carrier Dynamics in Organic-Inorganic Perovskite CH3NH3PbBr3. AB - Here, we investigate photoluminescence (PL) and time-resolved photoluminescence (TRPL) in CH3NH3PbBr3 perovskite under continuous illumination, using optical and electro-optical techniques. Under continuous excitation at constant intensity, PL intensity and PL decay (carrier recombination) exhibit excitation intensity dependent reductions in the time scale of seconds to minutes. The enhanced nonradiative recombination is ascribed to light activated negative ions and their accumulation which exhibit a slow dynamics in a time scale of seconds to minutes. The observed result suggests that the organic-inorganic hybrid perovskite is a mixed electronic-ionic semiconductor. The key findings in this work suggest that ions are photoactivated or electro-activated and their accumulation at localized sites can result in a change of carrier dynamics. The findings are therefore useful for the understanding of instability of perovskite solar cells and shed light on the necessary strategies for performance improvement. PMID- 26863287 TI - Implantation of Miniosmotic Pumps and Delivery of Tract Tracers to Study Brain Reorganization in Pathophysiological Conditions. AB - Pharmacological treatment in animal models of cerebral disease imposes the problem of repeated injection protocols that may induce stress in animals and result in impermanent tissue levels of the drug. Additionally, drug delivery to the brain is delicate due to the blood brain barrier (BBB), thus significantly reducing intracerebral concentrations of selective drugs after systemic administration. Therefore, a system that allows both constant drug delivery without peak levels and circumvention of the BBB is in order to achieve sufficiently high intracerebral concentrations of drugs that are impermeable to the BBB. In this context, miniosmotic pumps represent an ideal system for constant drug delivery at a fixed known rate that eludes the problem of daily injection stress in animals and that may also be used for direct brain delivery of drugs. Here, we describe a method for miniosmotic pump implantation and post operatory care that should be given to animals in order to successfully apply this technique. We embed the aforementioned experimental paradigm in standard procedures that are used for studying neuroplasticity within the brain of C57BL6 mice. Thus, we exposed animals to 30 min brain infarct and implanted with miniosmotic pumps connected to the skull via a cannula in order to deliver a pro plasticity drug. Behavioral testing was done during 30 days of treatment. After removal the animals received injections of anterograde tract tracers to analyze neuronal plasticity in the chronic phase of recovery. Results indicated that neuroprotection by the delivered drug was accompanied with increase in motor fibers crossing the midline of the brain at target structures. The results affirm the value of these techniques for drug administration and brain plasticity studies in modern neuroscience. PMID- 26863288 TI - Nanoparticles Self-Assembly Driven by High Affinity Repeat Protein Pairing. AB - Proteins are the most specific yet versatile biological self-assembling agents with a rich chemistry. Nevertheless, the design of new proteins with recognition capacities is still in its infancy and has seldom been exploited for the self assembly of functional inorganic nanoparticles. Here, we report on the protein directed assembly of gold nanoparticles using purpose-designed artificial repeat proteins having a rigid but modular 3D architecture. alphaRep protein pairs are selected for their high mutual affinity from a library of 10(9) variants. Their conjugation onto gold nanoparticles drives the massive colloidal assembly of free standing, one-particle thick films. When the average number of proteins per nanoparticle is lowered, the extent of self-assembly is limited to oligomeric particle clusters. Finally, we demonstrate that the aggregates are reversibly disassembled by an excess of one free protein. Our approach could be optimized for applications in biosensing, cell targeting, or functional nanomaterials engineering. PMID- 26863289 TI - Continuous Flow Magnesiation or Zincation of Acrylonitriles, Acrylates, and Nitroolefins. Application to the Synthesis of Butenolides. AB - Scalable continuous flow procedures are reported for the metalation and downstream functionalization of beta-substituted acrylates. The flow conditions allow the metalation of acrylonitriles, acrylates, and nitroolefins at 0.25-2.50 mmol/min conversion rates. Magnesiations can be performed with short residence times (1-20 min) and near-ambient temperature using TMPMgCl.LiCl. Further, high temperature zincation (<=90 degrees C) using TMPZnCl.LiCl is possible. This method allows a simple entry to 2(5H)-furanones by flow generation of magnesiated acrylates and a subsequent reaction with aldehydes. PMID- 26863290 TI - Cesium Lead Halide Perovskites with Improved Stability for Tandem Solar Cells. AB - A semiconductor that can be processed on a large scale with a bandgap around 1.8 eV could enable the manufacture of highly efficient low cost double-junction solar cells on crystalline Si. Solution-processable organic-inorganic halide perovskites have recently generated considerable excitement as absorbers in single-junction solar cells, and though it is possible to tune the bandgap of (CH3NH3)Pb(BrxI1-x)3 between 2.3 and 1.6 eV by controlling the halide concentration, optical instability due to photoinduced phase segregation limits the voltage that can be extracted from compositions with appropriate bandgaps for tandem applications. Moreover, these materials have been shown to suffer from thermal degradation at temperatures within the processing and operational window. By replacing the volatile methylammonium cation with cesium, it is possible to synthesize a mixed halide absorber material with improved optical and thermal stability, a stabilized photoconversion efficiency of 6.5%, and a bandgap of 1.9 eV. PMID- 26863291 TI - Crystallization-Dependent Luminescence Properties of Ce:LuPO4. AB - The luminescence properties of Ce:LuPO4 depend on both the Ce(3+) center and the host lattice. In this article, we studied the dependence of the luminescence properties of Ce:LuPO4 on both the doping concentration of Ce(3+) and the size and morphology of the LuPO4 matrix at micro- and nanosize regimes. The crystalline behavior of Ce:LuPO4, including its size and shape, was investigated via precursor transformation crystallization. On the basis of this crystallization approach, Ce:LuPO4 hollow nanospheres, nanorods, and regular tetrahedrons were obtained. For micro- and nanostructured Ce:LuPO4, the surface induced chemical bonding architecture can be effectively varied by controlling the size of the crystalline material and its geometry. Our experimental observations demonstrate that one-dimensional Ce:LuPO4 nanorods doped with 0.1 mol % Ce(3+) possess the best performance among the as-prepared samples. The significant anisotropy of Ce:LuPO4 nanorods can result in a larger specific surface area and enhanced luminescence properties. Moreover, the improved luminescence property of Ce:LuPO4 nanostructures can also be optimized by increasing the preferential anisotropic chemical bonding architecture to regulate the 5d level of Ce(3+). Our work also shows that the photoluminescence emission intensity of Ce:LuPO4 nanorods is increased as the surface area normal to their axial direction increases. From the standpoint of crystallization, the luminescence properties of Ce(3+) in nano- and microsize matrixes can be well optimized by controlling the crystalline behavior of the host lattice under proper synthesis conditions. PMID- 26863292 TI - Engagement in High-Risk Behaviors Among Young Adult Survivors of Childhood Cancer Compared to Healthy Same-Age Peers Surveyed in the National Longitudinal Study of Adolescent Health. AB - PURPOSE: This secondary data analysis compared smoking rates, alcohol consumption, and binge drinking, and examined risk factors for engaging in these behaviors among 90 young adult-aged childhood cancer survivors (CSS) with 15,490 young adults in the general population. METHODS: The sample was drawn from the National Longitudinal Study of Adolescent Health. The sampling distribution of these healthy matched young adults was estimated through the use of bootstrapping, which involved randomly repeated for 10,000 samples of healthy controls. RESULTS: The findings of repeated sampling analysis revealed that CCS were more likely to smoke daily (34.5% vs. 20.6 healthy matched controls; p = 0.03). The proportion of respondents who had any signs of alcohol abuse symptoms was 72.2% of CCS compared with 81.1% of matched controls (p = 0.16), while CCS with severe alcohol abuse was 51.1% compared with 59.1% of matched controls (p = 0.28). Whether they engaged in binge drinking in the past 12 months was 43.3% for CCS and 46.4% for healthy respondents. Logistic regression analyses were performed to examine predictors of smoking, alcohol use, and binge drinking among CCS. Smoking was very strongly associated with optimism. An optimism score of one unit higher was associated with a 39% reduction in odds of smoking (odd ratio [OR] = 0.61, p < 0.0001). Black CSS were less likely to smoke (OR = 0.15, p < 0.05). CCS in good health were more likely to binge drink (OR = 3.67, p < 0.05). CONCLUSIONS: Data generated from this secondary data analyses add to the evidence base about the engagement in high risk behaviors among young adult-aged CCS. These findings further emphasize the need for widespread, available effective theory-based screening guidelines and interventions. PMID- 26863293 TI - Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data. AB - Public data from ECHA online dossiers on 9,801 substances encompassing 326,749 experimental key studies and additional information on classification and labeling were made computable. Eye irritation hazard, for which the rabbit Draize eye test still represents the reference method, was analyzed. Dossiers contained 9,782 Draize eye studies on 3,420 unique substances, indicating frequent retesting of substances. This allowed assessment of the test's reproducibility test based on all substances tested more than once. There was a 10% chance of a non-irritant evaluation given after a prior severe-irritant result as given by UN GHS classification criteria. The most reproducible outcomes were the results negative (94% reproducible) and severe eye irritant (73% reproducible). To evaluate whether other GHS categorizations predict eye irritation we built a dataset of 5,629 substances (1,931 'irritant' and 3,698 'non-irritant'). The two best decision trees with up to three other GHS classifications resulted in balanced accuracies of 68% and 73%, i.e., in the rank order of the Draize rabbit eye test itself, but both use inhalation toxicity data ("May cause respiratory irritation"), which is not typically available. Next, a dataset of 929 substances with at least one Draize study was mapped to PubChem to compute chemical similarity using 2D conformational fingerprints and Tanimoto similarity. Using a minimum similarity of 0.7 and simple classification by the closest chemical neighbor resulted in balanced accuracy from 73% over 737 substances to 100% at a threshold of 0.975 over 41 substances. This represents a strong support of read across and (Q)SAR approaches in this area. PMID- 26863294 TI - Annual Surgeon Volume and Patient Outcomes Following Laparoscopic Totally Extraperitoneal Inguinal Hernia Repairs. AB - PURPOSE: Data on laparoscopic totally extraperitoneal inguinal hernia repairs (TEP-IHRs) suggest that approximately 250 operations are needed to gain mastery, but the annual volume required to maintain high-quality outcomes is unknown. MATERIALS AND METHODS: A retrospective review was performed of every patient undergoing a TEP-IHR at the Mayo Clinic (Rochester, MN) from 1995 to 2011. Analysis focused on the annual volume of 21 staff surgeons and their specific patient outcomes broken up into three groups: Group 1 (G1) (n = 1 surgeon) performed >30 repairs per year; Group 2 (G2) (n = 3 surgeons), 15-30 repairs; and Group 3 (G3) (n = 17), <15 repairs. RESULTS: In total, 1601 patients underwent 2410 TEP-IHRs, with no significant patient demographic differences among groups. Greater annual surgeon volume (G1 > G2 > G3) was associated with improved outcomes as shown by the respective rates for intra- (1%, 2.6%, and 5.6%) and postoperative (13%, 27%, and 36%) complications, need for overnight stay (17%, 23%, and 29%), and hernia recurrence (1%, 4%, and 4.3%) (all P < .05). Surgeons with greater annual operative volumes were more likely to operate on patients with bilateral and recurrent hernias. Surgeons performing at least 15 repairs per year (G1 and G2) showed improvements in quality metrics over time. CONCLUSIONS: Annual operative volumes of >30 repairs per year are associated with the highest quality outcomes for TEP-IHR. Operative volumes of at least 15 repairs per year are associated with improvements in quality metrics over time. Mentorship and operative assistance of low-volume TEP-IHR surgeons may be useful in improving patient outcomes. PMID- 26863295 TI - Hybrid Natural Orifice Translumenal Endoscopic Surgery Transvaginal Nephrectomy in a Low-Resource Setting. AB - INTRODUCTION: Hybrid natural orifice translumenal endoscopic surgery (NOTES((r)); American Society for Gastrointestinal Endoscopy [Oak Brook, IL] and Society of American Gastrointestinal and Endoscopic Surgeons [Los Angeles, CA]) reduces the invasiveness of conventional laparoscopic surgery and overcomes the limitation of pure NOTES, especially in the absence of angulated instruments. PATIENTS AND METHODS: The patients were 66-, 69-, and 32-year-old women with complaints of recurrent flank pain and urinary tract infection due to an obstructed nonfunctioning kidney. Materials used were standard laparoscopic instruments and a 30 degrees 10-mm high-definition laparoscope. Under general anesthesia, each patient was placed in a lithotomy position with the affected side up at 45 degrees . A Veress needle was initially inserted through the umbilicus and was later replaced with a 10-mm laparoscopic port, with an additional 5-mm port also inserted at the affected lower quadrant site. The patient was then positioned in a steep Trendelenburg position, and a 10-mm port was inserted through the posterior vaginal wall under direct vision from the abdominal cavity that was later used for the laparoscope. Nephrectomy proceeded despite noted severe adhesions, and the kidney was placed in the specimen retrieval bag. The vaginal port site was enlarged to 3 cm for extraction of the specimen. A Penrose drain was placed at the lower quadrant 5-mm trocar site. The vaginal wound was repaired using running 2-0 absorbable sutures. RESULTS: Three cases of transvaginal hybrid NOTES nephrectomy were successfully completed with a median operative time of 310 minutes and mean estimated blood loss of 300 mL. Median renal dimensions were as follows: craniocaudal, 10.2 (range, 10.6-9) cm; laterolateral, 6.5 (range, 7-5.3) cm; and anteroposterior, 4.8 (range, 6.5-3.9) cm. The patients resumed regular diet as early as Day 1 postoperatively. The drain was removed prior to discharge. The mean date of discharge was Day 3 postoperatively. There were no noted surgical complications according to the Clavien-Dindo grading system. CONCLUSIONS: Hybrid NOTES transvaginal nephrectomy is a feasible and reproducible procedure in selected patients regardless of laterality for better cosmesis, reduced postoperative pain, and early recovery. PMID- 26863296 TI - Laparoscopic Subxiphoid Hernia Repair with Intracorporeal Suturing of Mesh to the Diaphragm as a Means to Decrease Recurrence. AB - BACKGROUND: Subxiphoid hernias are a rare complication of median sternotomy with an incidence of 1%-4.2%. Repair of subxiphoid hernias is technically demanding with recurrence rates of 42% and 30% following open and laparoscopic repairs, respectively. We present a novel approach to the laparoscopic repair of subxiphoid hernias with improved overlap and fixation. MATERIALS AND METHODS: A novel technique for repairing subxiphoid hernias is described. The falciform ligament is dissected superiorly toward the diaphragm to allow proper subfascial positioning of the mesh with adequate overlap. Multiple nonabsorbable intracorporeal sutures are used to anchor the mesh to the diaphragm above the costal margins. Transfascial nonabsorbable sutures and tacks are used to fix the mesh to the anterior abdominal wall below the costal margin. RESULTS: We have used this method in 4 patients with a mean age of 60.5 years and a female to male ratio of 4:0. The average hernia defect size was 20.5 cm(2), and the average duration of operation was 93 minutes. There were no reported postoperative complications or evidence of recurrence at the 1-year follow-up. CONCLUSIONS: Laparoscopic repair of subxiphoid hernias can be safely accomplished with mesh sutured to the diaphragm for improved overlap and fixation with the goal of reducing recurrence rates. PMID- 26863297 TI - Adjuvant chemotherapy for rectal cancer: time to change the guidelines. PMID- 26863298 TI - Potential Impacts of Future Warming and Land Use Changes on Intra-Urban Heat Exposure in Houston, Texas. AB - Extreme heat events in the United States are projected to become more frequent and intense as a result of climate change. We investigated the individual and combined effects of land use and warming on the spatial and temporal distribution of daily minimum temperature (Tmin) and daily maximum heat index (HImax) during summer in Houston, Texas. Present-day (2010) and near-future (2040) parcel-level land use scenarios were embedded within 1-km resolution land surface model (LSM) simulations. For each land use scenario, LSM simulations were conducted for climatic scenarios representative of both the present-day and near-future periods. LSM simulations assuming present-day climate but 2040 land use patterns led to spatially heterogeneous temperature changes characterized by warmer conditions over most areas, with summer average increases of up to 1.5 degrees C (Tmin) and 7.3 degrees C (HImax) in some newly developed suburban areas compared to simulations using 2010 land use patterns. LSM simulations assuming present-day land use but a 1 degrees C temperature increase above the urban canopy (consistent with warming projections for 2040) yielded more spatially homogeneous metropolitan-wide average increases of about 1 degrees C (Tmin) and 2.5 degrees C (HImax), respectively. LSM simulations assuming both land use and warming for 2040 led to summer average increases of up to 2.5 degrees C (Tmin) and 8.3 degrees C (HImax), with the largest increases in areas projected to be converted to residential, industrial and mixed-use types. Our results suggest that urbanization and climate change may significantly increase the average number of summer days that exceed current threshold temperatures for initiating a heat advisory for metropolitan Houston, potentially increasing population exposure to extreme heat. PMID- 26863299 TI - Colon Cancer Tumorigenesis Initiated by the H1047R Mutant PI3K. AB - The phosphoinositide 3-kinase (PI3K) signaling pathway is critical for multiple important cellular functions, and is one of the most commonly altered pathways in human cancers. We previously developed a mouse model in which colon cancers were initiated by a dominant active PI3K p110-p85 fusion protein. In that model, well differentiated mucinous adenocarcinomas developed within the colon and initiated through a non-canonical mechanism that is not dependent on WNT signaling. To assess the potential relevance of PI3K mutations in human cancers, we sought to determine if one of the common mutations in the human disease could also initiate similar colon cancers. Mice were generated expressing the Pik3caH1047R mutation, the analog of one of three human hotspot mutations in this gene. Mice expressing a constitutively active PI3K, as a result of this mutation, develop invasive adenocarcinomas strikingly similar to invasive adenocarcinomas found in human colon cancers. These tumors form without a polypoid intermediary and also lack nuclear CTNNB1 (beta-catenin), indicating a non-canonical mechanism of tumor initiation mediated by the PI3K pathway. These cancers are sensitive to dual PI3K/mTOR inhibition indicating dependence on the PI3K pathway. The tumor tissue remaining after treatment demonstrated reduction in cellular proliferation and inhibition of PI3K signaling. PMID- 26863300 TI - Infant Mortality Risk and Paternity Certainty Are Associated with Postnatal Maternal Behavior toward Adult Male Mountain Gorillas (Gorilla beringei beringei). AB - Sexually selected infanticide is an important source of infant mortality in many mammalian species. In species with long-term male-female associations, females may benefit from male protection against infanticidal outsiders. We tested whether mountain gorilla (Gorilla beringei beringei) mothers in single and multi male groups monitored by the Dian Fossey Gorilla Fund's Karisoke Research Center actively facilitated interactions between their infants and a potentially protective male. We also evaluated the criteria mothers in multi-male groups used to choose a preferred male social partner. In single male groups, where infanticide risk and paternity certainty are high, females with infants <1 year old spent more time near and affiliated more with males than females without young infants. In multi-male groups, where infanticide rates and paternity certainty are lower, mothers with new infants exhibited few behavioral changes toward males. The sole notable change was that females with young infants proportionally increased their time near males they previously spent little time near when compared to males they had previously preferred, perhaps to encourage paternity uncertainty and deter aggression. Rank was a much better predictor of females' social partner choice than paternity. Older infants (2-3 years) in multi male groups mirrored their mothers' preferences for individual male social partners; 89% spent the most time in close proximity to the male their mother had spent the most time near when they were <1 year old. Observed discrepancies between female behavior in single and multi-male groups likely reflect different levels of postpartum intersexual conflict; in groups where paternity certainty and infanticide risk are both high, male-female interests align and females behave accordingly. This highlights the importance of considering individual and group-level variation when evaluating intersexual conflict across the reproductive cycle. PMID- 26863301 TI - Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naive Adolescent Depression. AB - BACKGROUND: Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD). This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naive adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 26 first-episode medication-naive MDD adolescents and 31 healthy controls (HC). Fractional anisotropy (FA) values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC) region showing significant differences between the two groups was identified. RESULTS: Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group. CONCLUSIONS: First-episode medication-naive adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD. PMID- 26863302 TI - Metabolomic and Transcriptomic Comparison of Solid-State and Submerged Fermentation of Penicillium expansum KACC 40815. AB - Penicillium spp. are known to harbor a wide array of secondary metabolites with cryptic bioactivities. However, the metabolomics of these species is not well understood in terms of different fermentation models and conditions. The present study involved metabolomics profiling and transcriptomic analysis of Penicillium expansum 40815 under solid-state fermentation (SSF) and submerged fermentation (SmF). Metabolite profiling was carried out using ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry with multivariate analysis, followed by transcriptomic analyses of differentially expressed genes. In principal component analysis, the metabolite profiling data was studied under different experimental sets, including SSF and SmF. The significantly different metabolites such as polyketide metabolites (agonodepside B, rotiorin, verrucosidin, and ochrephilone) and corresponding gene transcripts (polyketide synthase, aromatic prenyltransferase, and terpenoid synthase) were primarily detected under SmF conditions. In contrast, the meroterpenoid compounds (andrastin A and C) and their genes transcripts were exclusively detected under SSF conditions. We demonstrated that the metabolite production and its corresponding gene expression levels in P. expansum 40815 were significantly influenced by the varying growth parameters and the immediate environment. This study further provides a foundation to produce specific metabolites by regulating fermentation conditions. PMID- 26863303 TI - EGL-20/Wnt and MAB-5/Hox Act Sequentially to Inhibit Anterior Migration of Neuroblasts in C. elegans. AB - Directed neuroblast and neuronal migration is important in the proper development of nervous systems. In C. elegans the bilateral Q neuroblasts QR (on the right) and QL (on the left) undergo an identical pattern of cell division and differentiation but migrate in opposite directions (QR and descendants anteriorly and QL and descendants posteriorly). EGL-20/Wnt, via canonical Wnt signaling, drives the expression of MAB-5/Hox in QL but not QR. MAB-5 acts as a determinant of posterior migration, and mab-5 and egl-20 mutants display anterior QL descendant migrations. Here we analyze the behaviors of QR and QL descendants as they begin their anterior and posterior migrations, and the effects of EGL-20 and MAB-5 on these behaviors. The anterior and posterior daughters of QR (QR.a/p) after the first division immediately polarize and begin anterior migration, whereas QL.a/p remain rounded and non-migratory. After ~1 hour, QL.a migrates posteriorly over QL.p. We find that in egl-20/Wnt, bar-1/beta-catenin, and mab 5/Hox mutants, QL.a/p polarize and migrate anteriorly, indicating that these molecules normally inhibit anterior migration of QL.a/p. In egl-20/Wnt mutants, QL.a/p immediately polarize and begin migration, whereas in bar-1/beta-catenin and mab-5/Hox, the cells transiently retain a rounded, non-migratory morphology before anterior migration. Thus, EGL-20/Wnt mediates an acute inhibition of anterior migration independently of BAR-1/beta-catenin and MAB-5/Hox, and a later, possible transcriptional response mediated by BAR-1/beta-catenin and MAB 5/Hox. In addition to inhibiting anterior migration, MAB-5/Hox also cell autonomously promotes posterior migration of QL.a (and QR.a in a mab-5 gain-of function). PMID- 26863304 TI - Haemosporidian Parasites of Antelopes and Other Vertebrates from Gabon, Central Africa. AB - Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes. PMID- 26863305 TI - Long-Term Epidemiology of Streptococcus pneumoniae Serogroup 6 in a Region of Southern Europe with Special Reference to Serotype 6E. AB - Streptococcus pneumoniae serotype 6E has recently been described, but its long term epidemiology is not well known. From 1981-2013, 704 serogroup 6 clinical isolates were obtained in Gipuzkoa, Basque Country, Spain. All invasive and one in four non-invasive isolates were included. Overall, 75, 97, 51 and 45 serotypes 6A, 6B, 6C and 6E isolates, respectively, were detected. No serotype 6D isolates were identified. The prevalence of serotypes 6E and 6B, but not that of serotypes 6A and 6C, declined after the introduction of pneumococcal conjugate vaccines. Serotype 6E isolates showed the highest resistance rate. Most serotype 6E isolates were ST90. PMID- 26863306 TI - Ten Years of Complete Remission of Pulmonary Metastasis after Post-Cystectomy Palliative Cisplatin-Gemcitabine Chemotherapy with Gefitinib for Muscle Invasive Bladder Cancer: A Case Report. AB - Muscle-invasive bladder cancer (MIBC) is considered one of the most lethal malignancies with high metastatic potential. Usually, metastatic bladder cancer carries worse prognosis with a median survival rate of approximately 6 months, which can be prolonged for up to 14 months with palliative systemic chemotherapy. We present the case of a 61-year-old male patient diagnosed with localized MIBC 10 years ago. He underwent nerve-sparing radical cystectomy with ileal neobladder, but developed pulmonary metastatic disease 7 months postoperatively. Six cycles of gemcitabine/cisplatin combination chemotherapy with an addition of gefitinib as daily oral medication were administered within a randomized phase II clinical trial; this resulted in complete remission of the pulmonary metastases. Until now, the patient is still on gefitinib daily without any side effects. Although, the addition of gefitinib to standard systemic chemotherapy has not been shown to improve the survival in metastatic urothelial cancer, this case represents a very pleasant albeit uncommon long-term outcome. PMID- 26863307 TI - Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study. AB - BACKGROUND AND AIMS: To evaluate the National Immunisation Programme (NIP) a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC) areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier. METHODS: In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS) and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml) was used as minimum protective level. RESULTS: In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (p<0.05). On average, 82% (vs. 78% in the 1995/1996 serosurvey, p<0.05) of individuals from the NS born before introduction of diphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11) of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations) without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups. CONCLUSIONS: The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community after introduction in the Netherlands has not disappeared, despite national long-term high vaccination coverage. PMID- 26863308 TI - Anorexia Nervosa and Its Associated Endocrinopathy in Young People. AB - Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin-like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite-regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. PMID- 26863309 TI - The Utility of Core Needle Biopsy and Fine-Needle Aspiration in the Workup of Tumors of Suspected Mullerian Origin. AB - OBJECTIVES: Core needle biopsy (CNB) and fine-needle aspiration (FNA) for tumors of suspected Mullerian origin may prevent unnecessary laparotomies and allow patients the benefit of neoadjuvant chemotherapy. An assessment of the utility and limitations of CNB/FNA, with incorporation of current immunohistochemistry, is needed. STUDY DESIGN: Two hundred nineteen female patients with CNB/FNA of the omentum, pelvis, abdomen, adnexa, ovary, uterus, and fallopian tube were identified. From these, 30 consecutive CNB/FNA with corresponding surgical resection were reviewed to assess diagnostic agreement and identify potential diagnostic pitfalls. RESULTS: The most frequent diagnosis overall was adenocarcinoma (96/219; 43.8%), most commonly adenocarcinoma of gynecologic origin (65/219; 30%). Nondiagnostic or unsatisfactory material was present in a minority of cases (10/219; 5%). In the 30 CNB/FNA cases examined for diagnostic agreement with surgical resection, 24 (80%) had exact or essential agreement with the final diagnosis. Of the 23 cases that were positive and/or suspicious on cytology, 18 (78%) had neoadjuvant chemotherapy or radiation treatment prior to surgical resection. CONCLUSIONS: The majority of CNB/FNA for tumors of suspected Mullerian origin are diagnostic, correlate with the surgical resection, and contribute to management. A standard diagnostic algorithm is suggested. PMID- 26863310 TI - Electromagnetic Real Time Navigation in the Region of the Posterior Pelvic Ring: An Experimental In-Vitro Feasibility Study and Comparison of Image Guided Techniques. AB - BACKGROUND: Electromagnetic tracking is a relatively new technique that allows real time navigation in the absence of radiation. The aim of this study was to prove the feasibility of this technique for the treatment of posterior pelvic ring fractures and to compare the results with established image guided procedures. METHODS: Tests were performed in pelvic specimens (Sawbones(r)) with standardized sacral fractures (Type Denis I or II). A gel matrix simulated the operative approach and a cover was used to disable visual control. The electromagnetic setup was performed by using a custom made carbon reference plate and a prototype stainless steel K-wire with an integrated sensor coil. Four different test series were performed: Group OCT: Optical navigation using preoperative CT-scans; group O3D: Optical navigation using intraoperative 3-D fluoroscopy; group Fluoro: Conventional 2-D-fluoroscopy; group EMT: Electromagnetic navigation combined with a preoperative Dyna-CT. Accuracy of screw placement was analyzed by standardized postoperative CT-scan for each specimen. Operation time and intraoperative radiation exposure for the surgeon was documented. All data was analyzed using SPSS (Version 20, 76 Chicago, IL, USA). Statistical significance was defined as p< 0.05. RESULTS: 160 iliosacral screws were placed (40 per group). EMT resulted in a significantly higher incidence of optimal screw placement (EMT: 36/40) compared to the groups Fluoro (30/40; p< 0.05) and OCT (31/40; p< 0.05). Results between EMT and O3D were comparable (O3D: 37/40; n.s.). Also, the operation time was comparable between groups EMT and O3D (EMT 7.62 min vs. O3D 7.98 min; n.s.), while the surgical time was significantly shorter compared to the Fluoro group (10.69 min; p< 0.001) and the OCT group (13.3 min; p< 0.001). CONCLUSION: Electromagnetic guided iliosacral screw placement is a feasible procedure. In our experimental setup, this method was associated with improved accuracy of screw placement and shorter operation time when compared with the conventional fluoroscopy guided technique and compared to the optical navigation using preoperative CT-scans. Further studies are necessary to rule out drawbacks of this technique regarding ferromagnetic objects. PMID- 26863311 TI - gamma-Glutamyltransferase and Breast Cancer Risk Beyond Alcohol Consumption and Other Life Style Factors - A Pooled Cohort Analysis. AB - OBJECTIVE: Elevated gamma-Glutamyltransferase serum levels are associated with increased risk of overall cancer incidence and several site-specific malignancies. In the present prospective study we report on the associations of serum gamma-Glutamyltransferase with the risk of breast cancer in a pooled population-based cohort considering established life style risk factors. METHODS: Two cohorts were included in the present study, i.e. the Vorarlberg (n = 97,268) and the Malmoe cohort (n = 9,790). Cox proportional hazards regression models were fitted to estimate HRs for risk of breast cancer. RESULTS: In multivariate analysis adjusted for age, body mass index and smoking status, women with gamma Glutamyltransferase levels in the top quartile were at significantly higher risk for breast cancer compared to women in the lowest quartile (HR 1.21, 95% CI 1.09 to 1.35; p = 0.005). In the subgroup analysis of the Malmoe cohort, gamma Glutamyltransferase remained an independent risk factor for breast cancer when additionally considering alcohol intake. A statistically significant increase in risk was seen in women with gamma-Glutamyltransferase-levels in the top versus lowest quartile in a multivariate model adjusted for age, body mass index, smoking status, physical activity, parity, oral contraceptive-use and alcohol consumption (HR 1.37, 95% CI 1.11-1.69, p = 0.006). CONCLUSION: Our findings identified gamma-Glutamyltransferase as an independent risk factor for breast cancer beyond the consumption of alcohol and other life style risk factors. PMID- 26863312 TI - Preparing for Nontraditional Biothreats. AB - Biological threats consist of traditional, emerging, enhanced, and advanced threats, but current biodefense approaches focus almost entirely on a subset of traditional threats. There is an urgent need to develop a comprehensive, rational, and systematic plan to address and mitigate the broader risk space. Myriad possible strategies exist, but an ideal strategy will extend beyond a list of agents. This article proposes a functionality-based approach based on systematic identification of key functional elements, essentially focusing on mechanisms of what constitutes a threat: The key threat element is addressed directly instead of extensive characterization of ancillary details. Examples might include a potent toxin, long-term environmental stability, or a specific protein causing morbidity/mortality. By identifying the critical components leading to disease, limited time, efforts, and resources can be focused to address the greatest risks. Further, as future threats will likely contain critical aspects of known agents, this approach will potentially address a large area of uncharacterized risk space. Thus, focused research can buy down a large area of risk space while still addressing traditional threats and mission needs. Application of this strategy will move the field away from agent-based lists toward a more comprehensive hazard analysis and will position biodefense and health communities to prepare for the threats of the future. PMID- 26863313 TI - Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies. AB - Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL(r), YF VAX(r) and 2013-2014 Fluzone(r) vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of Biologics Evaluation and Research, with plaque reduction neutralization test performed by Focus Diagnostics, and with hemaglutination inhibition assay performed in-house at Sanofi Pasteur. Taken together, fADI assay appears to be a useful high throughput functional immunoassay for assessment of antibody-related neutralization of the viral infections for which pre-attachment neutralization pathway is predominant, such as polio, influenza, yellow fever and dengue. PMID- 26863314 TI - Are Participants Aware of the Type and Intensity of Transcranial Direct Current Stimulation? AB - Transcranial direct current stimulation (tDCS) is commonly used to alter cortical excitability but no experimental study has yet determined whether human participants are able to distinguish between the different types (anodal, cathodal, and sham) of stimulation. If they can then they are not blind to experimental conditions. We determined whether participants could identify different types of stimulation (anodal, cathodal, and sham) and current strengths after experiencing the sensations of stimulation during current onset and offset (which are associated with the most intense sensations) in Experiment 1 and also with a prolonged period of stimulation in Experiment 2. We first familiarized participants with anodal, cathodal, and sham stimulation at both 1 and 2 mA over either primary motor or visual cortex while their sensitivity to small changes in visual stimuli was assessed. The different stimulation types were then applied for a short (Experiment 1) or extended (Experiment 2) period with participants indicating the type and strength of the stimulation on the basis of the evoked sensations. Participants were able to identify the intensity of stimulation with shorter, but not longer periods, of stimulation at better than chance levels but identification of the different stimulation types was at chance levels. This result suggests that even after exposing participants to stimulation, and ensuring they are fully aware of the existence of a sham condition, they are unable to identify the type of stimulation from transient changes in stimulation intensity or from more prolonged stimulation. Thus participants are able to identify intensity of stimulation but not the type of stimulation. PMID- 26863315 TI - Pooled-Peptide Epitope Mapping Strategies Are Efficient and Highly Sensitive: An Evaluation of Methods for Identifying Human T Cell Epitope Specificities in Large Scale HIV Vaccine Efficacy Trials. AB - The interferon gamma, enzyme-linked immunospot (IFN-gamma ELISpot) assay is widely used to identify viral antigen-specific T cells is frequently employed to quantify T cell responses in HIV vaccine studies. It can be used to define T cell epitope specificities using panels of peptide antigens, but with sample and cost constraints there is a critical need to improve the efficiency of epitope mapping for large and variable pathogens. We evaluated two epitope mapping strategies, based on group testing, for their ability to identify vaccine-induced T-cells from participants in the Step HIV-1 vaccine efficacy trial, and compared the findings to an approach of assaying each peptide individually. The group testing strategies reduced the number of assays required by >7-fold without significantly altering the accuracy of T-cell breadth estimates. Assays of small pools containing 7-30 peptides were highly sensitive and effective at detecting single positive peptides as well as summating responses to multiple peptides. Also, assays with a single 15-mer peptide, containing an identified epitope, did not always elicit a response providing validation that 15-mer peptides are not optimal antigens for detecting CD8+ T cells. Our findings further validate pooling-based epitope mapping strategies, which are critical for characterizing vaccine-induced T-cell responses and more broadly for informing iterative vaccine design. We also show ways to improve their application with computational peptide:MHC binding predictors that can accurately identify the optimal epitope within a 15-mer peptide and within a pool of 15-mer peptides. PMID- 26863316 TI - Detection of a Tumor Suppressor Gene Variant Predisposing to Colorectal Cancer in an 18th Century Hungarian Mummy. AB - Mutations of the Adenomatous polyposis coli (APC) gene are common and strongly associated with the development of colorectal adenomas and carcinomas. While extensively studied in modern populations, reports on visceral tumors in ancient populations are scarce. To the best of our knowledge, genetic characterization of mutations associated with colorectal cancer in ancient specimens has not yet been described. In this study we have sequenced hotspots for mutations in the APC gene isolated from 18th century naturally preserved human Hungarian mummies. While wild type APC sequences were found in two mummies, we discovered the E1317Q missense mutation, known to be a colorectal cancer predisposing mutation, in a large intestine tissue of an 18th century mummy. Our data suggests that this genetic predisposition to cancer already existed in the pre-industrialization era. This study calls for similar investigations of ancient specimens from different periods and geographical locations to be conducted and shared for the purpose of obtaining a larger scale analysis that will shed light on past cancer epidemiology and on cancer evolution. PMID- 26863317 TI - Coarse-resolution Ecology of Etiological Agent, Vector, and Reservoirs of Zoonotic Cutaneous Leishmaniasis in Libya. AB - Cutaneous leishmaniasis ranks among the tropical diseases least known and most neglected in Libya. World Health Organization reports recognized associations of Phlebotomus papatasi, Psammomys obesus, and Meriones spp., with transmission of zoonotic cutaneous leishmaniasis (ZCL; caused by Leishmania major) across Libya. Here, we map risk of ZCL infection based on occurrence records of L. major, P. papatasi, and four potential animal reservoirs (Meriones libycus, Meriones shawi, Psammomys obesus, and Gerbillus gerbillus). Ecological niche models identified limited risk areas for ZCL across the northern coast of the country; most species associated with ZCL transmission were confined to this same region, but some had ranges extending to central Libya. All ENM predictions were significant based on partial ROC tests. As a further evaluation of L. major ENM predictions, we compared predictions with 98 additional independent records provided by the Libyan National Centre for Disease Control (NCDC); all of these records fell inside the belt predicted as suitable for ZCL. We tested ecological niche similarity among vector, parasite, and reservoir species and could not reject any null hypotheses of niche similarity. Finally, we tested among possible combinations of vector and reservoir that could predict all recent human ZCL cases reported by NCDC; only three combinations could anticipate the distribution of human cases across the country. PMID- 26863318 TI - Correction: Characterization of the Drosophila Group Ortholog to the Amino Terminus of the Alpha-Thalassemia and Mental Retardation X-Linked (ATRX) Vertebrate Protein. PMID- 26863320 TI - Males Under-Estimate Academic Performance of Their Female Peers in Undergraduate Biology Classrooms. AB - Women who start college in one of the natural or physical sciences leave in greater proportions than their male peers. The reasons for this difference are complex, and one possible contributing factor is the social environment women experience in the classroom. Using social network analysis, we explore how gender influences the confidence that college-level biology students have in each other's mastery of biology. Results reveal that males are more likely than females to be named by peers as being knowledgeable about the course content. This effect increases as the term progresses, and persists even after controlling for class performance and outspokenness. The bias in nominations is specifically due to males over-nominating their male peers relative to their performance. The over-nomination of male peers is commensurate with an overestimation of male grades by 0.57 points on a 4 point grade scale, indicating a strong male bias among males when assessing their classmates. Females, in contrast, nominated equitably based on student performance rather than gender, suggesting they lacked gender biases in filling out these surveys. These trends persist across eleven surveys taken in three different iterations of the same Biology course. In every class, the most renowned students are always male. This favoring of males by peers could influence student self-confidence, and thus persistence in this STEM discipline. PMID- 26863319 TI - Rearing Temperature Influences Adult Response to Changes in Mating Status. AB - Rearing environment can have an impact on adult behavior, but it is less clear how rearing environment influences adult behavior plasticity. Here we explore the effect of rearing temperature on adult mating behavior plasticity in the butterfly Bicyclus anynana, a species that has evolved two seasonal forms in response to seasonal changes in temperature. These seasonal forms differ in both morphology and behavior. Females are the choosy sex in cohorts reared at warm temperatures (WS butterflies), and males are the choosy sex in cohorts reared at cooler temperatures (DS butterflies). Rearing temperature also influences mating benefits and costs. In DS butterflies, mated females live longer than virgin females, and mated males live shorter than virgin males. No such benefits or costs to mating are present in WS butterflies. Given that choosiness and mating costs are rearing temperature dependent in B. anynana, we hypothesized that temperature may also impact male and female incentives to remate in the event that benefits and costs of second matings are similar to those of first matings. We first examined whether lifespan was affected by number of matings. We found that two matings did not significantly increase lifespan for either WS or DS butterflies relative to single matings. However, both sexes of WS but not DS butterflies experienced decreased longevity when mated to a non-virgin relative to a virgin. We next observed pairs of WS and DS butterflies and documented changes in mating behavior in response to changes in the mating status of their partner. WS but not DS butterflies changed their mating behavior in response to the mating status of their partner. These results suggest that rearing temperature influences adult mating behavior plasticity in B. anynana. This developmentally controlled behavioral plasticity may be adaptive, as lifespan depends on the partner's mating status in one seasonal form, but not in the other. PMID- 26863321 TI - Yoga for Adult Women with Chronic PTSD: A Long-Term Follow-Up Study. AB - INTRODUCTION: Yoga-the integrative practice of physical postures and movement, breath exercises, and mindfulness-may serve as a useful adjunctive component of trauma-focused treatment to build skills in tolerating and modulating physiologic and affective states that have become dysregulated by trauma exposure. A previous randomized controlled study was carried out among 60 women with chronic, treatment-resistant post-traumatic stress disorder (PTSD) and associated mental health problems stemming from prolonged or multiple trauma exposures. After 10 sessions of yoga, participants exhibited statistically significant decreases in PTSD symptom severity and greater likelihood of loss of PTSD diagnosis, significant decreases in engagement in negative tension reduction activities (e.g., self-injury), and greater reductions in dissociative and depressive symptoms when compared with the control (a seminar in women's health). The current study is a long-term follow-up assessment of participants who completed this randomized controlled trial. METHODS: Participants from the randomized controlled trial were invited to participate in long-term follow-up assessments approximately 1.5 years after study completion to assess whether the initial intervention and/or yoga practice after treatment was associated with additional changes. Forty-nine women completed the long-term follow-up interviews. Hierarchical regression analysis was used to examine whether treatment group status in the original study and frequency of yoga practice after the study predicted greater changes in symptoms and PTSD diagnosis. RESULTS: Group assignment in the original randomized study was not a significant predictor of longer-term outcomes. However, frequency of continuing yoga practice significantly predicted greater decreases in PTSD symptom severity and depression symptom severity, as well as a greater likelihood of a loss of PTSD diagnosis. CONCLUSIONS: Yoga appears to be a useful treatment modality; the greatest long term benefits are derived from more frequent yoga practice. PMID- 26863322 TI - Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1. AB - BACKGROUND: Transmission patterns of sexually-transmitted infections (STIs) could relate to the structure of the underlying sexual contact network, whose features are therefore of interest to clinicians. Conventionally, we represent sexual contacts in a population with a graph, that can reveal the existence of communities. Phylogenetic methods help infer the history of an epidemic and incidentally, may help detecting communities. In particular, phylogenetic analyses of HIV-1 epidemics among men who have sex with men (MSM) have revealed the existence of large transmission clusters, possibly resulting from within community transmissions. Past studies have explored the association between contact networks and phylogenies, including transmission clusters, producing conflicting conclusions about whether network features significantly affect observed transmission history. As far as we know however, none of them thoroughly investigated the role of communities, defined with respect to the network graph, in the observation of clusters. METHODS: The present study investigates, through simulations, community detection from phylogenies. We simulate a large number of epidemics over both unweighted and weighted, undirected random interconnected islands networks, with islands corresponding to communities. We use weighting to modulate distance between islands. We translate each epidemic into a phylogeny, that lets us partition our samples of infected subjects into transmission clusters, based on several common definitions from the literature. We measure similarity between subjects' island membership indices and transmission cluster membership indices with the adjusted Rand index. RESULTS AND CONCLUSION: Analyses reveal modest mean correspondence between communities in graphs and phylogenetic transmission clusters. We conclude that common methods often have limited success in detecting contact network communities from phylogenies. The rarely-fulfilled requirement that network communities correspond to clades in the phylogeny is their main drawback. Understanding the link between transmission clusters and communities in sexual contact networks could help inform policymaking to curb HIV incidence in MSMs. PMID- 26863323 TI - Ghrelin, GLP-1, and leptin responses during exposure to moderate hypoxia. AB - Severe hypoxia has been indicated to cause acute changes in appetite-related hormones, which attenuate perceived appetite. However, the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite have not been elucidated. Therefore, we examined the effects of moderate hypoxia on appetite-related hormonal regulation and perceived appetite. Eight healthy males (21.0 +/- 0.6 years; 173 +/- 2.3 cm; 70.6 +/- 5.0 kg; 23.4 +/- 1.1 kg/m(2)) completed two experimental trials on separate days: a rest trial in normoxia (FiO2 = 20.9%) and a rest trial in hypoxia (FiO2 = 15.0%). The experimental trials were performed over 7 h in an environmental chamber. Blood samples and scores of subjective appetite were collected over 7 h. Standard meals were provided 1 h (745 kcal) and 4 h (731 kcal) after initiating exposure to hypoxia or normoxia within the chamber. Although each meal significantly reduced plasma active ghrelin concentrations (P < 0.05), the response did not differ significantly between the trials over 7 h. No significant differences in the area under the curves for plasma active ghrelin concentrations over 7 h were observed between the two trials. No significant differences were observed in glucagon-like peptide 1 or leptin concentrations over 7 h between the trials. The subjective feeling of hunger and fullness acutely changed in response to meal ingestions. However, these responses were not affected by exposure to moderate hypoxia. In conclusion, 7 h of exposure to moderate hypoxia did not change appetite-related hormonal responses or perceived appetite in healthy males. PMID- 26863325 TI - Long-Term Potentiation: From CaMKII to AMPA Receptor Trafficking. AB - For more than 20 years, we have known that Ca(2+)/calmodulin-dependent protein kinase (CaMKII) activation is both necessary and sufficient for the induction of long-term potentiation (LTP). During this time, tremendous effort has been spent in attempting to understand how CaMKII activation gives rise to this phenomenon. Despite such efforts, there is much to be learned about the molecular mechanisms involved in LTP induction downstream of CaMKII activation. In this review, we highlight recent developments that have shaped our current thinking about the molecular mechanisms underlying LTP and discuss important questions that remain in the field. PMID- 26863324 TI - The Role of PVH Circuits in Leptin Action and Energy Balance. AB - Although it has been known for more than a century that the brain controls overall energy balance and adiposity by regulating feeding behavior and energy expenditure, the roles for individual brain regions and neuronal subtypes were not fully understood until recently. This area of research is active, and as such our understanding of the central regulation of energy balance is continually being refined as new details emerge. Much of what we now know stems from the discoveries of leptin and the hypothalamic melanocortin system. Hypothalamic circuits play a crucial role in the control of feeding and energy expenditure, and within the hypothalamus, the arcuate nucleus (ARC) functions as a gateway for hormonal signals of energy balance, such as leptin. It is also well established that the ARC is a primary residence for hypothalamic melanocortinergic neurons. The paraventricular hypothalamic nucleus (PVH) receives direct melanocortin input, along with other integrated signals that affect energy balance, and mediates the majority of hypothalamic output to control both feeding and energy expenditure. Herein, we review in detail the structure and function of the ARC PVH circuit in mediating leptin signaling and in regulating energy balance. PMID- 26863326 TI - Regulation of Renal Electrolyte Transport by WNK and SPAK-OSR1 Kinases. AB - The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. WNKs regulate the activity of the Na(+):Cl(-) cotransporter (NCC), the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), and other transport pathways. Interestingly, the modulation of NCC occurs via the phosphorylation by WNKs of other serine threonine kinases known as SPAK-OSR1. In contrast, the process of regulating the channels is independent of SPAK-OSR1. We present a review of the remarkable advances in this area in the past 10 years. PMID- 26863327 TI - Vascular Growth Factors and Glomerular Disease. AB - The glomerulus is a highly specialized microvascular bed that filters blood to form primary urinary filtrate. It contains four cell types: fenestrated endothelial cells, specialized vascular support cells termed podocytes, perivascular mesangial cells, and parietal epithelial cells. Glomerular cell-cell communication is critical for the development and maintenance of the glomerular filtration barrier. VEGF, ANGPT, EGF, SEMA3A, TGF-beta, and CXCL12 signal in paracrine fashions between the podocytes, endothelium, and mesangium associated with the glomerular capillary bed to maintain filtration barrier function. In this review, we summarize the current understanding of these signaling pathways in the development and maintenance of the glomerulus and the progression of disease. PMID- 26863328 TI - Introduction. PMID- 26863329 TI - A case series of dural venous sinus stenting in idiopathic intracranial hypertension: association of outcomes with optical coherence tomography. AB - : Purpose/Aim: Pseudotumor cerebri or idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure of unknown etiology. A subset of patients has shown benefit from endovascular dural venous sinus stenting (DVSS). We sought to identify a population of IIH patients who underwent DVSS to assess outcomes. MATERIALS AND METHODS: A retrospective study was performed to identify IIH patients with dural sinus stenosis treated with DVSS. Outcome measures included dural sinus pressure gradients, peripapillary retinal nerve fiber layer (RNFL) thickness using optical coherence tomography and improvement in symptoms. RESULTS: Seventeen patients underwent DVSS. Average pre- and post intervention pressure gradients were 23.06 and 1.18 mmHg, respectively (p < 0.0001). Sixteen (94%) noted improvement in headache, fourteen (82%) had visual improvement and all (100%) patients had improved main symptom. Of 11 patients with optical coherence tomography, 8 showed decreased RNFL thickness and 3 remained stable; furthermore, these 11 patients had improved vision with improved papilledema in 8, lack of pre-existing papilledema in 2 and stable, mild edema in 1 patient. CONCLUSIONS: Our series of patients with dural sinus stenosis demonstrated improvement in vision and reduction in RNFL thickness. DVSS appears to be a useful treatment for IIH patients with dural sinus stenosis. PMID- 26863330 TI - Chrysin treatment improves diabetes and its complications in liver, brain, and pancreas in streptozotocin-induced diabetic rats. AB - Chrysin (CH) is a natural flavonoid with pharmacological influences. The purpose of the current study was the assessment of possible protective effects of CH against oxidative damage in the serum, liver, brain, and pancreas of streptozotocin (STZ)- induced diabetic rats. In the present study, the rats were divided into the following groups of 8 animals each: control, untreated diabetic, 3 CH (20, 40, 80 mg/kg/day)-treated diabetic groups. To find out the modulations of cellular antioxidant defense systems, malondialdehyde (MDA) level and antioxidant enzymes including glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities were determined in the serum, liver, brain, and pancreas. STZ caused an elevation of glucose, MDA, TG, TC, LDL C and with reduction of HDL-C, total protein, SOD, CAT, and GST in the serum, liver, brain, and pancreas (p < 0.01). The findings showed that the significant elevation in the glucose, MDA, TG, TC, LDL-C and reduction of HDL-C, total protein, SOD, CAT, and GST were ameliorated in the CH-treated diabetic groups versus to the untreated groups, in a dose dependent manner (p < 0.05). The current study offers that CH may be recovered diabetes and its complications by modification of oxidative stress. PMID- 26863332 TI - Conducting Polymer-Based Catalysts. AB - Conducting polymers (CPs) have been widely applied as electrocatalysts and photocatalysts in energy-related systems, sensors, and environmental protection. This is mainly due to their promising catalytic activities, high conductivities, and unique electrochemical and optical properties. Furthermore, CPs can be cheaply and conveniently prepared in large scale via chemical or electrochemical approaches. In this Perspective, we review the recent advancements on the synthesis and applications of CP-based inherent and composite catalysts and CP derived heteroatom-doped carbon catalysts. The mechanisms of catalysis will be introduced, and the challenges of developing CP-based catalysts with practical importance will be discussed. PMID- 26863331 TI - An Operant Intra-/Extra-dimensional Set-shift Task for Mice. AB - Alterations in executive control and cognitive flexibility, such as attentional set-shifting abilities, are core features of several neuropsychiatric diseases. The most widely used neuropsychological tests for the evaluation of attentional set-shifting in human subjects are the Wisconsin Card Sorting Test (WCST) and the CANTAB Intra-/Extra-dimensional set shift task (ID/ED). These tasks have proven clinical relevance and have been modified and successfully adapted for research in animal models. However, currently available tasks for rodents present several limitations, mainly due to their manual-based testing procedures, which are hampering translational advances in psychiatric medicine. To overcome these limitations and to better mimic the original version in primates, we present the development of a novel operant-based two-chamber ID/ED "Operon" task for rodents. We demonstrated the effectiveness of this novel task to measure different facets of cognitive flexibility in mice including attentional set formation and shifting, and reversal learning. Moreover, we show the high flexibility of this task in which three different perceptual dimensions can be manipulated with a high number of stimuli cues for each dimension. This novel ID/ED Operon task can be an effective preclinical tool for drug testing and/or large genetic screening relevant to the study of executive dysfunction and cognitive symptoms found in psychiatric disorders. PMID- 26863333 TI - Racial/Ethnic Differences in Labor Outcomes with Prostaglandin Vaginal Inserts. AB - OBJECTIVE: The aim of this study is to compare labor outcomes across race/ethnicity in women undergoing prostaglandin labor induction. METHODS: Secondary analysis of misoprostol vaginal insert (MVI) trial, a double-blind, randomized, control trial of 1,308 patients comparing sustained release vaginal inserts containing dinoprostone 10 mg and misoprostol 50 mcg (MVI 50) or 100 mcg (MVI 100). RESULTS: Achievement of active labor and induction failures were similar across race/ethnicity. Cesareans were performed less frequently in whites (29 %) and Hispanics (24.5 %) compared to blacks (32.7 %) (adjusted odds ratio (aOR) 0.87, 95 % confidence interval (CI) 0.47-0.97, p = 0.03 and aOR 0.86, 95 % CI 0.44-0.97, p = 0.03, respectively). When compared to blacks, whites were less likely to undergo cesarean for non-reassuring fetal heart rate tracing (aOR 0.41, 95 % CI 0.25-0.66, p = 0.0003), as were Hispanics (aOR 0.38, 95 % CI 0.22-0.65, p = 0.0004). Postpartum hemorrhage occurred more frequently in Hispanics (8.8 %) versus blacks (4.1 %) and whites (OR 2.27, 95 % CI 0.23-0.82, p = 0.02 and OR 3.69, 95 % CI 0.14-0.51, p < 0.0001, respectively). Birth weights of black infants were lower than whites (p < 0.0001) and Hispanics (p = 0.0003). Neonatal outcomes did not differ between groups. CONCLUSION: Differences in labor induction outcomes with prostaglandin labor induction exist based on race/ethnicity. Blacks delivered smaller babies, were more likely to undergo cesarean, and have cesareans performed for non-reassuring fetal heart tracing compared to other groups. Hispanics were more likely to experience postpartum hemorrhage compared to the other races. PMID- 26863334 TI - Racial-Sex Disparities--A Challenging Battle Against Cancer Mortality in the USA. AB - Decline in US cancer mortality has recently been reported, based on either pooled mortality of all cancer sites or age-adjusted mortality rates of specific sites. While the former could be dominated by a few cancer sites and would not reflect that of other sites, the latter used the US 2000 Population as reference for age standardization, which was lack of justification. This study aimed to examine US cancer mortality trend and disparities in sites, races, and sex. We studied cancer incidence-based mortality by race and sex from 1974 to 2008 of cervix, prostate, colon and rectum, lung, leukemia, liver, pancreas, and stomach in the Surveillance, Epidemiology, and End Results database. We developed a model-based mortality rate and examined rate ratio of each calendar period to the first period within each race-sex group. Cancer mortality of cervix, colon and rectum, leukemia, and stomach declined in all groups. Prostate cancer increased first in all racial groups and decreased thereafter at different pace. Lung cancer declined among males of all races but increased among females. Liver cancer increased steadily fast among white and black females, doubled in whites and black males, and climbed slowly in other races. Pancreas cancer declined among black males and females, and changed little among others. Cancer mortality trend presents heterogeneity across sites, races, and sex. Recently observed mortality decline may not reflect every cancer site or group. More effort needs to focus on specific race-sex groups that had increasing lung and liver cancer mortality. PMID- 26863335 TI - Racial Differences in Chronic Conditions and Sociodemographic Characteristics Among High-Utilizing Veterans. AB - PURPOSE: African-Americans are disproportionally represented among high-risk, high-utilizing patients. To inform program development for this vulnerable population, the current study describes racial variation in chronic conditions and sociodemographic characteristics among high-utilizing patients in the Veterans Affairs Healthcare System (VA). METHODS: We identified the 5 % most costly Veterans who used inpatient or outpatient care at the VA during fiscal year 2010 (N = 237,691) based on costs of inpatient and outpatient care, pharmacy services, and VA-sponsored contract care. Patient costs and characteristics were abstracted from VA outpatient and inpatient data files. Racial differences in sociodemographic characteristics (age, sex, marital support, homelessness, and health insurance status) were assessed with chi-square tests. Racial differences in 32 chronic condition diagnoses were calculated as relative risk ratios. RESULTS: African-Americans represented 21 % of high-utilizing Veterans. African Americans had higher rates of homelessness (26 vs. 10 %, p < 0.001) and lower rates of supplemental health insurance (44 vs. 58 %, p < 0.001). The mean number of chronic conditions was similar across race. However, there were racial differences in the prevalence of specific chronic conditions, including a higher prevalence of HIV/AIDS (95 % confidence interval (CI) 4.86, 5.50) and schizophrenia (95 % CI 1.94, 2.07) and a lower prevalence of ischemic heart disease (95 % CI 0.57, 0.59) and bipolar disorder (95 % CI 0.78, 0.85) among African-American high-utilizing Veterans. CONCLUSION: Racial disparities among high-utilizing Veterans may differ from those found in the general population. Interventions should devote attention to social, environmental, and mental health issues in order to reduce racial disparities in this vulnerable population. PMID- 26863336 TI - The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries. AB - PURPOSE: We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men. METHODS: We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year. SES was measured using income and educational attainment. Sequential multivariate logistic regression models were performed to study whether health care access, patient-provider relationship, and cancer fatalism mediated the relationship between SES and PSA screening. RESULTS: Higher educational attainment was significantly associated with higher odds of PSA screening in the past year (odds ratio (OR) 2.08 for college graduate compared to less than high school graduate, 95 % confidence interval (CI) 1.03-4.24); income was not. Health care access and patient-provider communication did not alter the relationship between education and screening; however, beliefs regarding cancer fatalism partially mediated the observed relationship. CONCLUSION: Rates of prostate cancer screening among African American men vary by level of educational attainment; beliefs concerning cancer fatalism help explain this gradient. Understanding the determinants of cancer fatalism is a critical next step in building interventions that seek to ensure equitable access to prostate cancer screening. PMID- 26863337 TI - Differences in the Prevalence of Overweight Between 10-12-Year-old South Asian and Non-South Asian Children in Toronto, Ontario: Findings from Project BEAT. AB - OBJECTIVE: The objective of this study is to assess the prevalence of overweight among 10-12-year-old South Asian children in comparison to non-South Asian children. METHODS: This cross-sectional study obtained data from 16 schools in Toronto, Ontario. The analysis included 734 children (260 South Asian and 475 non South Asian) aged 10-12 years. Height and weight were measured, and body mass index (BMI; kg/m(2)) was calculated according to age- and sex-specific cut points established by the International Obesity Task Force (IOTF). RESULTS: The prevalence of overweight was significantly higher among South Asian children when compared to non-South Asian children (36.9 vs. 23.0 %; p < 0.001). Unadjusted, South Asian children exhibited increased odds for being overweight (OR = 1.96; CI = 1.41-2.73; p < 0.001) compared to non-South Asian children and persisted after the adjustment for socio-demographic covariates but did not remain significant after the inclusion of physical activity and sedentary behaviour variables. The adjusted odds for being overweight was significantly higher among South Asian boys (but not girls) compared to their non-South Asian counterparts (OR = 2.45; CI = 1.32-4.55; p < 0.0001). CONCLUSIONS: The prevalence of overweight differs by ethnic group and gender. South Asian boys have increased odds of being overweight compared to non-South Asian boys. Children of South Asian origin should receive focused attention in public health initiatives to reduce the risk of becoming overweight and the associated metabolic consequences. PMID- 26863338 TI - Race Attribution Modifies the Association Between Daily Discrimination and Major Depressive Disorder Among Blacks: the Role of Gender and Ethnicity. AB - OBJECTIVE: Although the association between discrimination and depression among Blacks is well-known, we do not know if this effect is influenced by race attribution. In this current study, we investigated the effect modification of race attribution on the association between everyday discrimination and major depressive disorder (MDD) among Blacks in the United States, and whether this effect modification is influenced by the intersection of ethnicity and gender. METHODS: With a cross-sectional design, this study used data from the National Survey of American Life (NSAL), 2001-2003. The study included a nationally representative sample of Blacks (n = 5,008), composed of 3,570 African Americans and 1,438 Caribbean Blacks. Everyday discrimination, two single-item measures of race attribution (race as the major barrier against upward social mobility, and race as the main cause for being discriminated against) and 12-month MDD were measured. In the first step, we fit logistic regressions to the pooled sample. In the next step, we ran regressions specific to the intersections of ethnicity and gender. Interaction between race attribution and discrimination were also entered into the models. RESULTS: Among Caribbean Black men, the belief that race is a major barrier against one's own upward social mobility modified the association between exposure to daily discrimination and MDD. In this group, the association between discrimination and MDD was weaker among those who believed that race is a major barrier against one's own upward social mobility. Race attribution did not modify the association between discrimination and MDD among African American men, African American women, and Caribbean Black women. The other measure of race attribution (race as the main cause of being discriminated against) did not modify the association between discrimination and MDD in any ethnicity by gender subgroups. CONCLUSIONS: Among Caribbean Black men, the link between everyday discrimination and depression may depend on seeing race as the main barrier against upward social mobility. Among African American men and women, however, the link between discrimination and MDD does not depend on race attribution. Our results suggest that ethnicity, gender, and race attribution may alter the association between discrimination and risk of MDD among Blacks. PMID- 26863339 TI - Does Patient Race/Ethnicity Influence Physician Decision-Making for Diagnosis and Treatment of Childhood Disruptive Behavior Problems? AB - Race/ethnic disparities in utilization of children's mental health care have been well documented and are particularly concerning given the long-term risks of untreated mental health problems (Institute of Medicine, 2003; Kessler et al. Am J Psychiatry 152:10026-1032, 1995). Research investigating the higher rates of unmet need among race/ethnic minority youths has focused primarily on policy, fiscal, and individual child or family factors that can influence service access and use. Alternatively, this study examines provider behavior as a potential influence on race/ethnic disparities in mental health care. The goal of the study was to examine whether patient (family) race/ethnicity influences physician diagnostic and treatment decision-making for childhood disruptive behavior problems. The study utilized an internet-based video vignette with corresponding survey of 371 randomly selected physicians from across the USA representing specialties likely to treat these patients (pediatricians, family physicians, general and child psychiatrists). Participants viewed a video vignette in which only race/ethnicity of the mother randomly varied (non-Hispanic White, Hispanic, and African American) and then responded to questions about diagnosis and recommended treatments. Physicians assigned diagnoses such as oppositional defiant disorder (48 %) and attention deficit disorder (63 %) to the child, but there were no differences in diagnosis based on race/ethnicity. The majority of respondents recommended psychosocial treatment (98 %) and/or psychoactive medication treatment (60 %), but there were no significant differences based on race/ethnicity. Thus, in this study using mock patient stimuli and controlling for other factors, such as insurance coverage, we did not find major differences in physician diagnostic or treatment decision-making based on patient race/ethnicity. PMID- 26863340 TI - Possible Contribution of PTSD to Altered Cortisol Activity in Young Adult Obese African-American Women. AB - OBJECTIVE: African-Americans have been found to experience increased rates of post-traumatic stress disorder (PTSD), obesity, and flatter diurnal cortisol slopes compared to other demographic groups. Further exploration, however, is needed to understand how PTSD impacts diurnal cortisol activity in obese African American women. The purpose of the current study is to examine the relationship between salivary cortisol levels and PTSD in a sample of obese young adult African-American women and to examine how depression and insomnia influence the relationship. METHODS: Thirty-four young adult African-American women (mean age = 24.0 years; mean BMI = 37.4 kg/m(2), 6/34 of the sample had a score of 40 or above on the PTSD Checklist (PCL) representing clinically significant PTSD) filled out questionnaires assessing PTSD, lifetime exposure to traumatic events, insomnia severity, and depression. A home-based assessment of salivary cortisol was provided upon awakening at 30 min and 1, 3, 6, and 12 h. RESULTS: There was a significant interaction between PTSD status and diurnal cortisol activity (p < 0.04). There were trends for higher cortisol levels at awakening (p < 0.051) and 30 min post-awakening (p < 0.059) with PTSD. The significance of the interaction between PTSD and cortisol was attenuated by co-varying for depression and insomnia (p > 0.05). CONCLUSION: PTSD, influenced by depression and insomnia symptoms, has an impact on diurnal cortisol activity in obese young adult African American women. PMID- 26863341 TI - Racial and Ethnic Disparities in Cardiovascular Disease: An Assessment of Obstetrician-Gynecologists' Knowledge, Attitudes, and Practice Patterns. AB - BACKGROUND: African American and Hispanic women are disproportionately affected by cardiovascular disease (CVD) and its many risk factors. Obstetrician gynecologists (OB/GYNs) play an integral role in well-woman care and have a unique opportunity to provide CVD counseling and screening to these at-risk and underserved groups. OBJECTIVE: To assess whether OB/GYN race/ethnicity and OB/GYN practices with increasing minority patient populations predicted differences in OB/GYNs' knowledge, attitudes, and practice patterns relevant to racial/ethnic disparities in CVD. This study also sought to determine provider and patient related barriers to CVD care. METHOD: A questionnaire on CVD was mailed to 273 members of The American College of Obstetricians and Gynecologists in March-July 2013. RESULTS: African American and Hispanic OB/GYNs and OB/GYN practices with increasing minority patient populations were more knowledgeable of CVD disparities. These OB/GYNs reported greater concern for minority women's CVD risk relative to White OB/GYNs. Overall, OB/GYNs appear less knowledgeable and concerned with Hispanics' increased CVD risk relative to African Americans'. The most commonly reported provider and patient-related barriers to CVD care were time constraints, patient nonadherence to treatment recommendations, and inadequate training. CONCLUSION: It is likely that minority OB/GYNs and those with practices with increasing minority patient populations have greater exposure to women at risk for CVD. Dissemination of educational information regarding Hispanic women's CVD risk profile may improve OB/GYN knowledge, counseling, and screening. Increased training in CVD and multicultural competency during medical school and residency should help OB/GYNs overcome what they report as primary barriers to CVD care. PMID- 26863342 TI - Determinants of Low Health Literacy Among Asian-American and Pacific Islanders in California. AB - BACKGROUND: Health literacy is a marker for how patients obtain, comprehend, communicate, and apply complex health information. Few studies exist on determinants of low health literacy among Asian-American and Pacific Islanders. The purpose of this exploratory study was to identify key determinants of low health literacy in this population using the 2007 California Health Interview Survey, a population-based survey. METHODS: Low health literacy was defined as reporting either prescription bottle or written information from the doctor as being "somewhat difficult" or "very difficult" to understand, or reporting having a hard time understanding their doctor. Survey weighted univariate and multivariable regression analyses were conducted. RESULTS: A total of 4045 participants were included in the study, representing 3,156,711 Asian-American and Pacific Islander adults in California. Factors associated with low health literacy were being male, low socioeconomic status, limited English language proficiency, and being foreign born. CONCLUSION: Results of this study highlight the current burden of low health literacy among Asian-American and Pacific Islander population and the associated factors. Targeted public health efforts to improve health literacy are needed among Asian-American and Pacific Islanders. PMID- 26863343 TI - A Novel Microsurgical Model for Heterotopic, En Bloc Chest Wall, Thymus, and Heart Transplantation in Mice. AB - Exploration of novel strategies in organ transplantation to prolong allograft survival and minimizing the need for long-term maintenance immunosuppression must be pursued. Employing vascularized bone marrow transplantation and co transplantation of the thymus have shown promise in this regard in various animal models. Vascularized bone marrow transplantation allows for the uninterrupted transfer of donor bone marrow cells within the preserved donor microenvironment, and the incorporation of thymus tissue with vascularized bone marrow transplantation has shown to increase T-cell chimerism ultimately playing a supportive role in the induction of immune regulation. The combination of solid organ and vascularized composite allotransplantation can uniquely combine these strategies in the form of a novel transplant model. Murine models serve as an excellent paradigm to explore the mechanisms of acute and chronic rejection, chimerism, and tolerance induction, thus providing the foundation to propagate superior allograft survival strategies for larger animal models and future clinical application. Herein, we developed a novel heterotopic en bloc chest wall, thymus, and heart transplant model in mice using a cervical non-suture cuff technique. The experience in syngeneic and allogeneic transplant settings is described for future broader immunological investigations via an instructional manuscript and video supplement. PMID- 26863344 TI - BRAF analysis before surgery for papillary thyroid carcinoma: correlation with clinicopathological features and prognosis in a single-institution prospective experience. AB - BACKGROUND: Risk stratification in patients with papillary thyroid carcinoma (PTC) currently relies on postoperative parameters. Testing for BRAF mutations preoperatively may serve as a novel tool for identifying PTC patients at risk of persistence/recurrence after surgery. METHODS: The study involved 185 consecutive patients with a histological diagnosis of PTC and BRAF analysis performed on thyroid fine-needle aspiration biopsy (FNAB). We assessed BRAF status in FNAB specimens obtained before thyroidectomy for PTC, and examined its association with the clinicopathological characteristics identified postoperatively, and with outcome after a mean 55+/-15 months of follow-up. RESULTS: One hundred and fifteen of 185 (62%) PTCs carried a BRAF mutation. Univariate analysis showed that BRAF status correlated with the histological variant of PTC, cancer size, and stage at diagnosis, but not with gender, age, multifocality, or lymph node involvement. BRAF-mutated cases had a higher prevalence of persistent/recurrent disease by the end of the follow-up (11% vs. 8%), but this difference was not statistically significant. The Kaplan-Meier curve shows that among the patients with persistent/recurrent disease, BRAF-mutated patients needed a second treatment earlier than patients with BRAF wild-type, although the difference did not completely reach the statistical significance. CONCLUSIONS: Our study confirmed that preoperatively-identified BRAF mutation are associated with certain pathological features of PTC that correlate with prognosis. We speculate that it has a role in identifying PTCs that would generally be considered low risk but that may reveal an aggressive behavior during their follow-up. PMID- 26863345 TI - Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases. AB - Clear evidence supports a role for circulating and locally-produced osteocalcin (OC) in the pathophysiology of cardiovascular (CV) lesions and CV risk, also in combination with metabolic changes, including type 2 diabetes mellitus (T2DM). Reduced plasma OC levels are associated with greater incidence of pathological CV changes, like arterial and valvular calcification, coronary and carotid atherosclerosis and increased carotid intima-media thickness. The actual relationship between OC levels and incidence of major CV events is, however, still unclear. Moreover, reduced circulating OC levels have been mostly associated with insulin resistance, metabolic syndrome or T2DM, indicating relevant OC actions on pancreatic beta-cells and insulin secretion and activity. Based on these observations, this review article will attempt to summarize the current evidence on the potential usefulness of circulating OC as a biomarker for CV and metabolic risk, also evaluating the currently open issues in this area of research. PMID- 26863346 TI - An International Standard for holotranscobalamin (holoTC): international collaborative study to assign a holoTC value to the International Standard for vitamin B12 and serum folate. AB - BACKGROUND: Investigation of possible B12 and folate deficiencies requires measurement of these vitamins in serum. There is evidence that holotranscobalamin (holoTC), the active portion of B12 available to cells, is a more specific marker of early B12 deficiency than total B12. The availability of immunoassays for holoTC prompted an international collaborative study to assign a holoTC value to the World Health Organization (WHO) 1st International Standard (IS) for vitamin B12 and serum folate, 03/178. METHODS: The IS, 03/178, and three serum samples with different holoTC levels were assayed by 12 laboratories in eight countries using manual and automated immunoassays for holoTC; one laboratory additionally performed an in-house assay. Fourteen sets of data were analysed. RESULTS: Overall, the IS, 03/178, and the three serum samples demonstrated assay linearity and parallelism. An overall geometric mean (GM) holoTC value of 106.8 pmol/L was obtained for 03/178, with an inter-laboratory geometric coefficient of variation (GCV) of 10.5%. There was a reduction in inter-laboratory variability when the holoTC levels in the serum samples were determined relative to the IS with an assigned holoTC value rather than to the assays' calibration. Accelerated degradation studies showed that 03/178 was sufficiently stable to serve as an IS for holoTC. CONCLUSIONS: The WHO Expert Committee on Biological Standardization endorsed the proposal to assign a holoTC value of 107 pmol/L to 03/178, corresponding to 0.107 pmol per ampoule, for use as the 1st IS for vitamin B12, serum folate, and holoTC. PMID- 26863347 TI - Pharmacogenetics and pharmacogenomics as tools in cancer therapy. AB - Pharmacogenetics and pharmacogenomics (PGx) are rapidly growing fields that aim to elucidate the genetic basis for the interindividual differences in drug response. PGx approaches have been applied to many anticancer drugs in an effort to identify relevant inherited or acquired genetic variations that may predict patient response to chemotherapy and targeted therapies. In this article, we discuss the advances in the field of cancer pharmacogenetics and pharmacogenomics, driven by the recent technological advances and new revolutionary massive sequencing technologies and their application to elucidate the genetic bases for interindividual drug response and the development of biomarkers able to personalize drug treatments. Specifically, we present recent progress in breast cancer molecular classifiers, cell-free circulating DNA as a prognostic and predictive biomarker in cancer, patient-derived tumor xenograft models, chronic lymphocytic leukemia genomic landscape, and current pharmacogenetic advances in colorectal cancer. This review is based on the lectures presented by the speakers of the symposium "Pharmacogenetics and Pharmacogenomics as Tools in Cancer Therapy" from the VII Conference of the Spanish Pharmacogenetics and Pharmacogenomics Society (SEFF), held in Madrid (Spain) on April 21, 2015. PMID- 26863348 TI - Neural Responses to Physical Characteristics of a High-velocity, Low-amplitude Spinal Manipulation: Effect of Thrust Direction. AB - STUDY DESIGN: Electrophysiological recordings were obtained from proprioceptors in deep lumbar paraspinal muscles of anesthetized cats during high-velocity low amplitude spinal manipulation (HVLA-SM). OBJECTIVE: To determine how thrust direction of an HVLA-SM affects neural input from back musculature. SUMMARY OF BACKGROUND DATA: A clinician's ability to apply the thrust of an HVLA-SM in a specified direction is considered an important component of its optimal delivery. However, previous biomechanical studies indicate that the shear force component of the thrust vector is not actually transmitted to paraspinal tissues deep to the thoracolumbar fascia because the skin-fascia interface is frictionless. METHODS: Neural activity from muscle spindles in the multifidus and longissimus muscles was recorded from L6 dorsal rootlets in 18 anesthetized cats. After preload to the spinal tissues, HVLA-SMs (100-ms thrust duration) were applied through the intact skin overlying the L6 lamina. Thrusts were applied at angles oriented perpendicularly to the back and obliquely at 15 degrees and 30 degrees medialward or cranialward using a 6 * 6 Latin square design with three replicates. The normal force component was kept constant at 21.3 N. HVLA-SMs were preceded and followed by simulated spinal movement applied to the L6 vertebra. Changes in mean instantaneous discharge frequency (DeltaMIF) of muscle spindles were determined both during the thrust and spinal movement. RESULTS: DeltaMIFs during the HVLA-SM thrust were significantly greater in response to all thrust directions compared with the preload alone, but there was no difference in DeltaMIF for any of the thrust directions during the HVLA-SM. HVLA-SM decreased some of the responses to simulated spinal movement but thrust direction had no effect on these changes. CONCLUSION: The shear force component of an HVLA-SM's thrust vector is not transmitted to the underlying vertebra sufficient to activate muscle spindles of the attached muscles. Implications for clinical practice and clinical research are discussed. LEVEL OF EVIDENCE: N/A. PMID- 26863349 TI - Polygraphic Recording Procedure for Measuring Sleep in Mice. AB - Recording of the epidural electroencephalogram (EEG) and electromyogram (EMG) in small animals, like mice and rats, has been pivotal to study the homeodynamics and circuitry of sleep-wake regulation. In many laboratories, a cable-based sleep recording system is used to monitor the EEG and EMG in freely behaving mice in combination with computer software for automatic scoring of the vigilance states on the basis of power spectrum analysis of EEG data. A description of this system is detailed herein. Steel screws are implanted over the frontal cortical area and the parietal area of 1 hemisphere for monitoring EEG signals. In addition, EMG activity is monitored by the bilateral placement of wires in both neck muscles. Non-rapid eye movement (Non-REM; NREM) sleep is characterized by large, slow brain waves with delta activity below 4 Hz in the EEG, whereas a shift from low frequency delta activity to a rapid low-voltage EEG in the theta range between 6 and 10 Hz can be observed at the transition from NREM to REM sleep. By contrast, wakefulness is identified by low- to moderate-voltage brain waves in the EEG trace and significant EMG activity. PMID- 26863350 TI - A World Free of Polio--The Final Steps. PMID- 26863351 TI - Standardizing Patient Outcomes Measurement. PMID- 26863352 TI - Is Dementia in Decline? Historical Trends and Future Trajectories. PMID- 26863353 TI - Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. AB - BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. METHODS: Caplacizumab, an anti-von Willebrand factor humanized single-variable domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. RESULTS: Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. CONCLUSIONS: Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; ClinicalTrials.gov number, NCT01151423.). PMID- 26863354 TI - Incidence of Dementia over Three Decades in the Framingham Heart Study. AB - BACKGROUND: The prevalence of dementia is expected to soar as the average life expectancy increases, but recent estimates suggest that the age-specific incidence of dementia is declining in high-income countries. Temporal trends are best derived through continuous monitoring of a population over a long period with the use of consistent diagnostic criteria. We describe temporal trends in the incidence of dementia over three decades among participants in the Framingham Heart Study. METHODS: Participants in the Framingham Heart Study have been under surveillance for incident dementia since 1975. In this analysis, which included 5205 persons 60 years of age or older, we used Cox proportional-hazards models adjusted for age and sex to determine the 5-year incidence of dementia during each of four epochs. We also explored the interactions between epoch and age, sex, apolipoprotein E epsilon4 status, and educational level, and we examined the effects of these interactions, as well as the effects of vascular risk factors and cardiovascular disease, on temporal trends. RESULTS: The 5-year age- and sex adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88). The prevalence of most vascular risk factors (except obesity and diabetes) and the risk of dementia associated with stroke, atrial fibrillation, or heart failure have decreased over time, but none of these trends completely explain the decrease in the incidence of dementia. CONCLUSIONS: Among participants in the Framingham Heart Study, the incidence of dementia has declined over the course of three decades. The factors contributing to this decline have not been completely identified. (Funded by the National Institutes of Health.). PMID- 26863355 TI - Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis. AB - BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.). PMID- 26863356 TI - Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma. AB - Antigen-driven selection has been implicated in the pathogenesis of monoclonal gammopathies. Patients with Gaucher's disease have an increased risk of monoclonal gammopathies. Here we show that the clonal immunoglobulin in patients with Gaucher's disease and in mouse models of Gaucher's disease-associated gammopathy is reactive against lyso-glucosylceramide (LGL1), which is markedly elevated in these patients and mice. Clonal immunoglobulin in 33% of sporadic human monoclonal gammopathies is also specific for the lysolipids LGL1 and lysophosphatidylcholine (LPC). Substrate reduction ameliorates Gaucher's disease associated gammopathy in mice. Thus, long-term immune activation by lysolipids may underlie both Gaucher's disease-associated gammopathies and some sporadic monoclonal gammopathies. PMID- 26863357 TI - CLINICAL PRACTICE. Urinary Tract Infections in Older Men. PMID- 26863358 TI - IMAGES IN CLINICAL MEDICINE. Madelung's Disease. PMID- 26863359 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 4-2016. A 58-Year-Old Woman with a Skin Ulcer, Fever, and Lymphadenopathy. PMID- 26863360 TI - Von Willebrand Factor--A New Target for TTP Treatment? PMID- 26863361 TI - Cardiometabolic Risks and Obesity in the Young. PMID- 26863362 TI - Cardiometabolic Risks and Obesity in the Young. PMID- 26863363 TI - Cardiometabolic Risks and Obesity in the Young. PMID- 26863364 TI - Cardiometabolic Risks and Obesity in the Young. PMID- 26863365 TI - A Leadless Cardiac Pacemaker. PMID- 26863366 TI - A Leadless Cardiac Pacemaker. PMID- 26863367 TI - A Leadless Cardiac Pacemaker. PMID- 26863368 TI - Trends in Metastatic Breast and Prostate Cancer. PMID- 26863369 TI - Trends in Metastatic Breast and Prostate Cancer. PMID- 26863370 TI - Trends in Metastatic Breast and Prostate Cancer. PMID- 26863371 TI - Trends in Metastatic Breast and Prostate Cancer. PMID- 26863372 TI - Probable Hospital Cluster of H7N9 Influenza Infection. PMID- 26863373 TI - IMAGES IN CLINICAL MEDICINE. Scalp Necrosis Associated with Giant-Cell Arteritis. PMID- 26863374 TI - A single session of open kinetic chain movements emphasizing speed improves speed of movement and modifies postural control in stroke. AB - Little attention has been given to training speed of movement, even though functional activities require quick submaximal contractions. Closed kinetic chain (CKC) exercises are considered more functional; however, the best method for training speed is not known. A single bout of open kinetic chain (OKC) exercises emphasizing speed was performed to determine whether movement velocity and muscle activation would improve in a single session and whether the improvements transfer to a physiological balance task. Eleven participants <1 year post-stroke performed an arm raise task before and after a single session of fast OKC exercises. Surface electromyography (EMG) from soleus (SOL), tibialis anterior (TA), biceps femoris (BF) and rectus femoris (RF) muscles, peak velocity and average power were recorded during the OKC exercises. EMG from SOL, TA, BF and RF and center of pressure (COP) velocity were measured during arm raise task. At the end of the OKC exercises, velocity, power and TA, BF and RF EMG area increased. The arm acceleration and BF EMG area increased significantly during the arm raise. The improvements observed at the end of the OKC exercises transferred to the arm raise task. The improvements in balance were comparable to those previously seen after CKC exercises. PMID- 26863375 TI - Human Platelet Lysate as a Replacement for Fetal Bovine Serum in Limbal Stem Cell Therapy. AB - PURPOSE: To evaluate the use of human platelet lysate (HPL) as an alternative supplement for limbal explant culture. METHODS: Culture media were prepared using either 10% pooled HPL (PHPL), single donor HPL, or fetal bovine serum (FBS). Limbal tissues, obtained from the Minnesota Lions Eye Bank, were cultured in each medium on plastic plates or on denuded amniotic membrane (AM). Immunofluorescence staining was performed for ABCG2, tumor protein p63alpha, and cytokeratin 3 (K3). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used to evaluate the expression of ABCG2 and p63. Limbal explants grown in each medium were labeled with bromodeoxyuridine (BrdU) to assess the proliferative capacity in each medium. Concentration of growth factors including epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta), and platelet derived growth factor (PDGF) in HPL and PHPL was compared to that in human serum (HS). RESULTS: Immunofluorescence staining on AM showed prominent expression of ABCG2, p63alpha but sparse expression of K3 in HPL and PHPL supplemented medium. Real time-PCR showed 1.7 fold higher expression of ABCG2 in PHPL supplemented medium (p = 0.03), and similar expression of p63 in HPL and PHPL supplemented medium compared to FBS medium. The proliferation assay showed that LSCs retained their proliferative potential in HPL supplemented medium. Higher concentration of growth factors were found in HPL, compared to HS. CONCLUSIONS: Human platelet lysate has higher concentration of grown factors and is effective in maintaining growth and stem cell phenotype of corneal limbal explant cultures. PMID- 26863376 TI - From microbes to fish the next revolution in food production. AB - Increasing global population and the consequent increase in demand for food are not a new story. Agroindustrial activities such as livestock help meet this demand. Aquaculture arose decades ago and revolutionized the agroindustrial activity as a significant food generator. However, like livestock, aquaculture is based on finite resources and has been accused of being unsustainable. Abandoning aquaculture is not an option considering the food, foreign exchange, and employment it generates, and therefore must be reinvented. Among the many alternatives suggested to make aquaculture more sustainable, microorganisms have been highlighted as a direct food source for cultured fish and crustaceans, a strategy that promises to revolutionize aquaculture by eliminating waste. Considering waste, as part of a cycle, it can increase stock densities and reduce emissions of contaminants and operational costs. PMID- 26863377 TI - Comments on "Efficacy of Stone Density on Noncontrast Computed Tomography in Predicting the Outcome of Extracorporeal Shock Wave Lithotripsy for Patients With Pancreatic Stones" by Ohyama et al. PMID- 26863378 TI - Reply to Xie S, Mai G. Comments on Comments on "Efficacy of Stone Density on Noncontrast Computed Tomography in Predicting the Outcome of Extracorporeal Shock Wave Lithotripsy for Patients With Pancreatic Stones" by Ohyama et al. PMID- 26863379 TI - Tertiary Lymphoid Tissue Occurs in the Porcine Pancreas. PMID- 26863380 TI - L-Carnitine Supplementation Improved Hepatic Steatosis After Pancreatectomy. PMID- 26863381 TI - A Case of Pancreatic Adenosquamous Carcinoma Obstructing the Common Bile and Pancreatic Ducts, Duodenum, and Gastric Outlet. PMID- 26863383 TI - Intestinal Lymphangiestasia With Hennekam Syndrome. PMID- 26863382 TI - Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation. AB - Protein-protein interactions (PPIs) are intimately involved in almost all biological processes and are linked to many human diseases. Therefore, there is a major effort to target PPIs in basic research and in the pharmaceutical industry. Protein-protein interfaces are usually large, flat, and often lack pockets, complicating the discovery of small molecules that target such sites. Alternative targeting approaches using antibodies have limitations due to poor oral bioavailability, low cell-permeability, and production inefficiency. Using peptides to target PPI interfaces has several advantages. Peptides have higher conformational flexibility, increased selectivity, and are generally inexpensive. However, peptides have their own limitations including poor stability and inefficiency crossing cell membranes. To overcome such limitations, peptide cyclization can be performed. Cyclization has been demonstrated to improve peptide selectivity, metabolic stability, and bioavailability. However, predicting the bioactive conformation of a cyclic peptide is not trivial. To overcome this challenge, one attractive approach it to screen a focused library to screen in which all backbone cyclic peptides have the same primary sequence, but differ in parameters that influence their conformation, such as ring size and position. We describe a detailed protocol for synthesizing a library of backbone cyclic peptides targeting specific parasite PPIs. Using a rational design approach, we developed peptides derived from the scaffold protein Leishmania receptor for activated C-kinase (LACK). We hypothesized that sequences in LACK that are conserved in parasites, but not in the mammalian host homolog, may represent interaction sites for proteins that are critical for the parasites' viability. The cyclic peptides were synthesized using microwave irradiation to reduce reaction times and increase efficiency. Developing a library of backbone cyclic peptides with different ring sizes facilitates a systematic screen for the most biological active conformation. This method provides a general, fast, and facile way to synthesize cyclic peptides. PMID- 26863385 TI - Aberrance of Serum Zinc and Free Copper Level in Wilson Disease. PMID- 26863384 TI - Endoscopic Evaluation in Children With End-Stage Liver Disease-Associated Portal Hypertension Awaiting Liver Transplant. AB - OBJECTIVES: Routine oesophago-gastro-duodenoscopy (OGD) pre-liver transplantation (LT) for evaluation and management of gastrointestinal (GI) pathology, in particular GI varices secondary to portal hypertension, is common practice in adult LT programmes. There is no universal consensus for this practice in children. We report our endoscopic experience in children with end-stage liver disease (ESLD) pre-LT. METHODS: Retrospective audit of LT database and review of OGD findings of patients who had undergone endoscopy preceding LT. RESULTS: Of 69 patients with ESLD, 50 (72.4%) had pre-LT OGD, 37 of which were done electively, whereas the remaining 13 were event driven. Forty-eight (96%) patients who underwent OGD had abnormalities, in which 38 (76%) patients had varices and 23 (46%) had portal hypertensive gastropathy. Eleven (22%) patients required therapeutic intervention at initial OGD either with endoscopic variceal band ligation or endoscopic sclerotherapy. Compared with the group who underwent elective OGDs, the group who had event-driven OGDs had a significantly higher requirement for endoscopic intervention (P < 0.0001), occurrence of rebleeding (P < 0.029) and requirement for repeat OGDs (P = 0.014). There was no significant difference in terms of patient (P = 0.2746) or graft survival (P = 0.3192) between the 2 groups. CONCLUSIONS: The role of pre-LT OGDs in patients with ESLD associated with portal hypertension is possibly limited to control of bleeding during episodes of GI bleed, where the aim would be to stabilize the patient until eventual LT. Multicentre prospective studies are required to provide more evidence on the use of routine endoscopy for pre-LT assessment in children. PMID- 26863386 TI - 2-Year-Old with a Limp and Suspected Non-Accidental Injury. PMID- 26863388 TI - MicroRNA indicators of follicular steroidogenesis. AB - MicroRNAs (miRNAs) can provide useful biomarkers of tissue function. The aim of the present study was to determine, in bovine follicles (n = 66; diameter 4-22 mm), the relationship among several indices of steroidogenesis and levels of 15 miRNAs previously identified to be associated with follicle development. Oestradiol levels, the oestradiol : progesterone (E : P) ratio and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression were strongly correlated with each other (rho > 0.8) and with LH/choriogonadotropin receptor (LHCGR) expression (rho >= 0.6; P < 0.01). Levels of nine different miRNAs in the follicular wall were correlated (P < 0.01) with oestradiol, the E : P ratio and CYP19A1, with miR-873 showing the strongest correlation in each case (rho > 0.7). Analyses of follicular fluid miRNAs identified miR-202 as correlated with oestradiol, the E : P ratio and CYP19A1 (rho > 0.5; P < 0.01). When considering all follicle end-points together, we found that using a cut-off value of E : P = 1 overestimated the number of oestrogen-inactive follicles, whereas using CYP19A1 as a classifier provided a clearer separation of follicle samples based on oestrogen activity, in agreement with the E : P ratio, LHCGR expression and levels of miR-873 and miR-202. In conclusion, we identified miR-873 and miR-202 as miRNAs whose levels in follicular tissues can be used as indicators of steroidogenic capacity in bovine. We showed that these or other gene expression parameters, in addition or alternatively to the E : P ratio, should be used to accurately classify follicles based on steroidogenic capacity. PMID- 26863387 TI - Inverting the Diagnostic Pyramid in Celiac Disease: HLA Typing for Screening Suspects of Celiac Disease. PMID- 26863389 TI - First principles modeling of Mo6S9 nanowires via condensation of Mo4S6 clusters and the effect of iodine doping on structural and electronic properties. AB - By employing first principles DFT calculations, we propose a new stable model for Mo6S9 nanowires (NWs) obtained by condensing tetrahedral Mo4S6 clusters rather than octahedral Mo6S8 clusters, which are known as magic clusters in the Mo-S polyhedral cluster family. The pristine NW is found to be metallic and its local structure and physical properties can be tuned by doping of iodine atoms. This doping increases the number of Mo-Mo bonds in the NW, thus, Mo4 tetrahedra are initially fused to the Mo6 octahedron, and then, to the Mo8 dodecahedron. Further, a close correlation among the Mo-Mo bonding in the local structure, mechanical and electronic properties, is observed from our study. Finally, the stability of the pristine and iodine doped Mo8S12-xIx NW structures obtained from condensation of Mo4 tetrahedra are found to be quite comparable with that of already reported Mo6S9-xIx NWs with Mo6 octahedra as building blocks. PMID- 26863391 TI - A very peculiar family of N-heterocyclic phosphines: unusual structures and the unique reactivity of 1,3,2-diazaphospholenes. AB - This Perspective gives an account of the peculiar electronic and molecular structures of N-heterocyclic phosphines featuring either a single 1,3,2 diazaphospholene (DAP) ring with an exocyclic P-substituent X or two DAP rings linked by a P-P bond (bis-diazaphospholenyls), respectively, and their impact on the chemical properties of these molecules. The bonding situation in simple DAPs is epitomized by strong hyperconjugation between endocyclic pi-type electrons and the exocyclic P-X bond. This interaction may induce a perceptible ionic polarization of the P-X bond which can persist even in the limit of a vanishing electronegativity gradient between P and X, and becomes visible in unusual geometric distortions of molecular structures and a unique chemical behaviour. Structural distortions are particularly evident in bond lengthening effects in P halogen and P-phosphino derivatives R2P-DAP (with R2P ? DAP) which span the whole range from covalent molecules to contact ion pairs with a close relation to frustrated Lewis-pairs. The most significant impact on the chemical properties is found for P-phosphino- and P-hydrogen derivatives where reactions at substantially accelerated rates or totally new reaction modes can be observed, and new stoichiometric and first catalytic processes exploiting these features are currently emerging. The recently discovered bis-diazaphospholenyls differ from the simple derivatives as their central bond remains unpolarised as a consequence of the symmetric molecular structure. The occurrence of low-energy P P bond homolysis that was nonetheless observed in one case is according to the results of thermochemical studies of P-P bond fission reactions attributable to the effects of steric congestion and induces chemical reactivity that can be considered complementary to that of the simple R2P-DAPs. Some concluding remarks will pay attention to a facet of DAP reactivity that has so far been widely neglected but is currently receiving increasing attention, namely well-defined ring-opening processes. PMID- 26863390 TI - Motor control exercise for acute non-specific low back pain. AB - BACKGROUND: Motor control exercise (MCE) is used by healthcare professionals worldwide as a common treatment for low back pain (LBP). However, the effectiveness of this intervention for acute LBP remains unclear. OBJECTIVES: To evaluate the effectiveness of MCE for patients with acute non-specific LBP. SEARCH METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), four other databases and two trial registers from their inception to April 2015, tracked citations and searched reference lists. We placed no limitations on language nor on publication status. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) examining the effectiveness of MCE for patients with acute non-specific LBP. We considered trials comparing MCE versus no treatment, versus another type of treatment or added as a supplement to other interventions. Primary outcomes were pain intensity and disability. Secondary outcomes were function, quality of life and recurrence. DATA COLLECTION AND ANALYSIS: Two review authors screened for potentially eligible studies, assessed risk of bias and extracted data. A third independent review author resolved disagreements. We examined MCE in the following comparisons: (1) MCE versus spinal manipulative therapy; (2) MCE versus other exercises; and (3) MCE as a supplement to medical management. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to assess the quality of evidence. For missing or unclear information, we contacted study authors. We considered the following follow-up intervals: short term (less than three months after randomisation); intermediate term (at least three months but within 12 months after randomisation); and long term (12 months or longer after randomisation). MAIN RESULTS: We included three trials in this review (n = 197 participants). Study sample sizes ranged from 33 to 123 participants. Low quality evidence indicates no clinically important differences between MCE and spinal manipulative therapy for pain at short term and for disability at short term and long term. Low-quality evidence also suggests no clinically important differences between MCE and other forms of exercise for pain at short or intermediate term and for disability at intermediate term or long term follow-up. Moderate-quality evidence shows no clinically important differences between MCE and other forms of exercise for disability at short term follow-up. Finally, very low-quality evidence indicates that addition of MCE to medical management does not provide clinically important improvement for pain or disability at short term follow-up. For recurrence at one year, very low-quality evidence suggests that MCE and medical management decrease the risk of recurrence by 64% compared with medical management alone. AUTHORS' CONCLUSIONS: We identified only three small trials that also evaluated different comparisons; therefore, no firm conclusions can be drawn on the effectiveness of MCE for acute LBP. Evidence of very low to moderate quality indicates that MCE showed no benefit over spinal manipulative therapy, other forms of exercise or medical treatment in decreasing pain and disability among patients with acute and subacute low back pain. Whether MCE can prevent recurrences of LBP remains uncertain. PMID- 26863392 TI - A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration. AB - Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID- 26863393 TI - Eu-doped ZnO-HfO2 hybrid nanocrystal-embedded low-loss glass-ceramic waveguides. AB - We report on the sol-gel fabrication, using a dip-coating technique, of low-loss Eu-doped 70SiO2 -[Formula: see text] HfO2-xZnO (x = 2, 5, 7 and 10 mol%) ternary glass-ceramic planar waveguides. Transmission electron microscopy and grazing incident x-ray diffraction experiments confirm the controlled growth of hybrid nanocrystals with an average size of 3 nm-25 nm, composed of ZnO encapsulated by a thin layer of nanocrystalline HfO2, with an increase of ZnO concentration from x = 2 mol% to 10 mol% in the SiO2-HfO2 composite matrix. The effect of crystallization on the local environment of Eu ions, doped in the ZnO-HfO2 hybrid nanocrystal-embedded glass-ceramic matrix, is studied using photoluminescence spectra, wherein an intense mixed-valence state (divalent as well as trivalent) emission of Eu ions is observed. The existence of Eu(2+) and Eu(3+) in the SiO2 HfO2-ZnO ternary matrix is confirmed by x-ray photoelectron spectroscopy. Importantly, the Eu[Formula: see text]-doped ternary waveguides exhibit low propagation losses (0.3 +/- 0.2 dB cm(-1) at 632.8 nm) and optical transparency in the visible region of the electromagnetic spectrum, which makes ZnO-HfO2 nanocrystal-embedded SiO2-HfO2-ZnO waveguides a viable candidate for the development of on-chip, active, integrated optical devices. PMID- 26863394 TI - Liver transplantation today: still severe problems to solve! PMID- 26863395 TI - Oxidative addition of an aromatic ortho C-H bond of tetraphosphine to asymmetric diiridium(i) centres. AB - Reactions of a tetraphosphine, meso bis{[(diphenylphosphinomethyl)phenyl]phosphino}propane (dpmppp), with [IrCl(cod)]2 and CO (1 atm) or isocyanide (RNC) in the presence of NH4PF6 at 80 100 degrees C in dichloromethane/acetonitrile/acetone and/or methanol mixed solvents afforded asymmetric diiridium(ii) complexes, [Ir2(H)(Cl)(MU-(dpmppp-H) kappaP(4)C)(CO)3]PF6 (1) and [Ir2(H)(MU-(dpmppp-H)-kappaP(4)C)(RNC)4)]-(PF6)2 (R = 2,6-xylyl (2), 2,4,6-mesityl (3); dpmppp-H = {PPh(o C6H4)CH2P(Ph)(CH2)3P(Ph)CH2PPh2}(-)). A similar reaction with (t)BuNC resulted in the formation of a mononuclear Ir(III) complex of [Ir(H)(dpmppp kappaP(3))((t)BuNC)2](PF6)2 (4). Complexes 1-3 were characterized by ESI mass spectrometry, (1)H and (31)P NMR spectroscopy and X-ray diffraction analyses. They were found to consist of cis/trans-P,P asymmetric Ir(II)-Ir(II) bonded dinuclear structures derived from oxidative addition of an ortho C-H bond of dpmppp (Ir-Ir = 2.8044(2) A (1), 2.8569(2) A (2), and 2.8524(5) A (3)), resulting in a [IrPCCIr] intermetallic cyclometal-bridge and a terminal hydride. DFT calculations indicated the presence of Ir-Ir, Ir-H, and Ir-Cortho covalent bonds. Initial stages of the reactions with CO and XylNC at room temperature were investigated by (31)P{(1)H} NMR spectroscopy and found to contain a symmetrical Ir(I) dinuclear unit with dpmppp that was readily transformed into 1 and 2 upon heating. The Ir intermediate with XylNC, [Ir2(XylNC)4(MU-dpmppp)](PF6)2 (6), was isolated and characterized by X-ray crystallography and DFT calculations as an electron-deficient 32e(-) Ir species involving a Ir(I)->Ir(I) dative bond (2.7989(5) A). The reaction pathways from 6 to 2 were investigated by DFT calculations. The present study suggested that a novel oxidative addition of an ortho C-H bond proceeded on the cis/trans-P,P asymmetric diiridium(i) scaffold supported by the tetraphosphine, dpmppp, which was assumed to be facilitated by dimetal cooperation with switching Ir->Ir dative interactions. PMID- 26863396 TI - Ultraviolet broadband light scattering for optically-trapped submicron-sized aerosol particles. AB - We describe a broadband light scattering setup for the characterization of size and refractive index of single submicron-to-micron sized aerosol particles. Individual particles are isolated in air by a quadruple Bessel beam optical trap or a counter-propagating optical tweezer. The use of very broadband radiation in the wavelength range from 320 to 700 nm covering the ultraviolet region allows to size submicron particles. We show that a broad wavelength range is required to determine the particle radius and the refractive index with an uncertainty of several nanometers and ~ 0.01, respectively. The smallest particle radius that can be accurately determined lies around 300 nm. Wavelength-dependent refractive index data over a broad range are obtained, including the ultraviolet region where corresponding data are rare. Four different applications are discussed: (1) the sizing of submicron polystyrene latex spheres, (2) the evaporation of binary glycerol water droplets, (3) hydration/dehydration cycling of aqueous potassium carbonate droplets, and (4) photochemical reactions of oleic acid droplets. PMID- 26863397 TI - A density functional theory protocol for the calculation of redox potentials of copper complexes. AB - A density functional theory (DFT) protocol for the calculation of redox potentials of copper complexes is developed based on 13 model copper complexes. The redox potentials are calculated in terms of Gibbs free energy change of the redox reaction at the theory level of CAM-B3LYP/6-31+G(d,p)/SMD, with the overall Gibbs free energy change being partitioned into the Gibbs free energy change of the gas phase reaction and the Gibbs free energy change of solvation. In addition, the calculated Gibbs free energy change of solvation is corrected by a unified correction factor of -0.258 eV as the second-layer Gibbs free energy change of solvation and other interactions for each redox reaction. And an empirical Gibbs free energy change of solvation at -0.348 eV is applied to each water molecule if the number of inner-sphere water molecule changes during the redox reaction. Satisfactory agreements between the DFT calculated and experimental results are obtained, with a maximum absolute error at 0.197 V, a mean absolute error at 0.114 V and a standard deviation at 0.133 V. Finally, it is concluded that the accurate prediction of redox potentials is dependent on the accurate prediction of geometrical structures as well as on geometrical conservation during the redox reaction. PMID- 26863398 TI - Minimally Invasive Versus Open Pancreatoduodenectomy: Systematic Review and Meta analysis of Comparative Cohort and Registry Studies. AB - OBJECTIVE: This study aimed to appraise and to evaluate the current evidence on minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy only in comparative cohort and registry studies. BACKGROUND: Outcomes after MIPD seem promising, but most data come from single-center, noncomparative series. METHODS: Comparative cohort and registry studies on MIPD versus open pancreatoduodenectomy published before August 23, 2015 were identified systematically and meta-analyses were performed. Primary endpoints were mortality and International Study Group on Pancreatic Fistula grade B/C postoperative pancreatic fistula (POPF). RESULTS: After screening 2293 studies, 19 comparative cohort studies (1833 patients) with moderate methodological quality and 2 original registry studies (19,996 patients) were included. For cohort studies, the median annual hospital MIPD volume was 14. Selection bias was present for cancer diagnosis. No differences were found in mortality [odds ratio (OR) = 1.1, 95% confidence interval (CI) = 0.6-1.9] or POPF [(OR) = 1.0, 95% CI = 0.8 to 1.3]. Publication bias was present for POPF. MIPD was associated with prolonged operative times [weighted mean difference (WMD) = 74 minutes, 95% CI = 29-118], but lower intraoperative blood loss (WMD = -385 mL, 95% CI = -616 to -154), less delayed gastric emptying (OR = 0.6, 95% = CI 0.5-0.8), and shorter hospital stay (WMD = -3 days, 95% CI = -5 to -2). For registry studies, the median annual hospital MIPD volume was 2.5. Mortality after MIPD was increased in low-volume hospitals (7.5% vs 3.4%; P = 0.003). CONCLUSIONS: Outcomes after MIPD seem promising in comparative cohort studies, despite the presence of bias, whereas registry studies report higher mortality in low-volume centers. The introduction of MIPD should be closely monitored and probably done only within structured training programs in high-volume centers. PMID- 26863401 TI - A Failed Late-Stage Epimerization Thwarts an Approach to Ineleganolide. AB - Significant efforts were made to complete a synthesis of the complex norcembranoid ineleganolide via a seemingly attractive strategy involving late stage creation of the central seven-membered ring. While the two key enantioenriched building blocks were made via high-yielding sequences and their convergent union was efficient, the critical C4-C5 bond of this sterically congested natural product could never be forged. Several interesting examples of unexpected acid-base behavior and unanticipated proximity-induced reactivity accounted for most of the problems in the execution of the synthesis plan. PMID- 26863402 TI - Stem cell-like Xenopus Embryonic Explants to Study Early Neural Developmental Features In Vitro and In Vivo. AB - Understanding the genetic programs underlying neural development is an important goal of developmental and stem cell biology. In the amphibian blastula, cells from the roof of the blastocoel are pluripotent. These cells can be isolated, and programmed to generate various tissues through manipulation of genes expression or induction by morphogens. In this manuscript protocols are described for the use of Xenopus laevis blastocoel roof explants as an assay system to investigate key in vivo and in vitro features of early neural development. These protocols allow the investigation of fate acquisition, cell migration behaviors, and cell autonomous and non-autonomous properties. The blastocoel roof explants can be cultured in a serum-free defined medium and grafted into host embryos. This transplantation into an embryo allows the investigation of the long-term lineage commitment, the inductive properties, and the behavior of transplanted cells in vivo. These assays can be exploited to investigate molecular mechanisms, cellular processes and gene regulatory networks underlying neural development. In the context of regenerative medicine, these assays provide a means to generate neural derived cell types in vitro that could be used in drug screening. PMID- 26863403 TI - Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors. AB - Many protein kinases are valid drug targets in oncology because they are key components of signal transduction pathways. The number of clinical kinase inhibitors is on the rise, but these molecules often exhibit polypharmacology, potentially eliciting desired and toxic effects. Therefore, a comprehensive assessment of a compound's target space is desirable for a better understanding of its biological effects. The enzyme ferrochelatase (FECH) catalyzes the conversion of protoporphyrin IX into heme and was recently found to be an off target of the BRAF inhibitor Vemurafenib, likely explaining the phototoxicity associated with this drug in melanoma patients. This raises the question of whether FECH binding is a more general feature of kinase inhibitors. To address this, we applied a chemical proteomics approach using kinobeads to evaluate 226 clinical kinase inhibitors for their ability to bind FECH. Surprisingly, low or submicromolar FECH binding was detected for 29 of all compounds tested and isothermal dose response measurements confirmed target engagement in cells. We also show that Vemurafenib, Linsitinib, Neratinib, and MK-2461 reduce heme levels in K562 cells, verifying that drug binding leads to a loss of FECH activity. Further biochemical and docking experiments identified the protoporphyrin pocket in FECH as one major drug binding site. Since the genetic loss of FECH activity leads to photosensitivity in humans, our data strongly suggest that FECH inhibition by kinase inhibitors is the molecular mechanism triggering photosensitivity in patients. We therefore suggest that a FECH assay should generally be part of the preclinical molecular toxicology package for the development of kinase inhibitors. PMID- 26863404 TI - Modification of Titanium Substrates with Chimeric Peptides Comprising Antimicrobial and Titanium-Binding Motifs Connected by Linkers To Inhibit Biofilm Formation. AB - Bacterial adhesion and biofilm formation are the primary causes of implant associated infection, which is difficult to eliminate and may induce failure in dental implants. Chimeric peptides with both binding and antimicrobial motifs may provide a promising alternative to inhibit biofilm formation on titanium surfaces. In this study, chimeric peptides were designed by connecting an antimicrobial motif (JH8194: KRLFRRWQWRMKKY) with a binding motif (minTBP-1: RKLPDA) directly or via flexible/rigid linkers to modify Ti surfaces. We evaluated the binding behavior of peptides using quartz crystal microbalance (QCM) and atomic force microscopy (AFM) techniques and investigated the effect of the modification of titanium surfaces with these peptides on the bioactivity of Streptococcus gordonii (S. gordonii) and Streptococcus sanguis (S. sanguis). Compared with the flexible linker (GGGGS), the rigid linker (PAPAP) significantly increased the adsorption of the chimeric peptide on titanium surfaces (p < 0.05). Concentration-dependent adsorption is consistent with a single Langmuir model, whereas time-dependent adsorption is in line with a two-domain Langmuir model. Additionally, the chimeric peptide with the rigid linker exhibited more effective antimicrobial ability than the peptide with the flexible linker. This finding was ascribed to the ability of the rigid linker to separate functional domains and reduce their interference to the maximum extent. Consequently, the performance of chimeric peptides with specific titanium-binding motifs and antimicrobial motifs against bacteria can be optimized by the proper selection of linkers. This rational design of chimeric peptides provides a promising alternative to inhibit the formation of biofilms on titanium surfaces with the potential to prevent peri implantitis and peri-implant mucositis. PMID- 26863406 TI - T Cells Capture Bacteria by Transinfection from Dendritic Cells. AB - Recently, we have shown, contrary to what is described, that CD4(+) T cells, the paradigm of adaptive immune cells, capture bacteria from infected dendritic cells (DCs) by a process called transinfection. Here, we describe the analysis of the transinfection process, which occurs during the course of antigen presentation. This process was unveiled by using CD4(+) T cells from transgenic OTII mice, which bear a T cell receptor (TCR) specific for a peptide of ovoalbumin (OVAp), which therefore can form stable immune complexes with infected dendritic cells loaded with this specific OVAp. The dynamics of green fluorescent protein (GFP) expressing bacteria during DC-T cell transmission can be monitored by live-cell imaging and the quantification of bacterial transinfection can be performed by flow cytometry. In addition, transinfection can be quantified by a more sensitive method based in the use of gentamicin, a non-permeable aminoglycoside antibiotic killing extracellular bacteria but not intracellular ones. This classical method has been used previously in microbiology to study the efficiency of bacterial infections. We hereby explain the protocol of the complete process, from the isolation of the primary cells to the quantification of transinfection. PMID- 26863407 TI - Alzheimer's Disease and Social Work Practice: Implications of Advances in Neurosciences for Social Workers. PMID- 26863408 TI - Merging Single-Atom-Dispersed Silver and Carbon Nitride to a Joint Electronic System via Copolymerization with Silver Tricyanomethanide. AB - Herein, we present an approach to create a hybrid between single-atom-dispersed silver and a carbon nitride polymer. Silver tricyanomethanide (AgTCM) is used as a reactive comonomer during templated carbon nitride synthesis to introduce both negative charges and silver atoms/ions to the system. The successful introduction of the extra electron density under the formation of a delocalized joint electronic system is proven by photoluminescence measurements, X-ray photoelectron spectroscopy investigations, and measurements of surface zeta potential. At the same time, the principal structure of the carbon nitride network is not disturbed, as shown by solid-state nuclear magnetic resonance spectroscopy and electrochemical impedance spectroscopy analysis. The synthesis also results in an improvement of the visible light absorption and the development of higher surface area in the final products. The atom-dispersed AgTCM-doped carbon nitride shows an enhanced performance in the selective hydrogenation of alkynes in comparison with the performance of other conventional Ag-based materials prepared by spray deposition and impregnation-reduction methods, here exemplified with 1-hexyne. PMID- 26863409 TI - pK(a) Values of Titrable Amino Acids at the Water/Membrane Interface. AB - Peptides and proteins protonation equilibrium is strongly influenced by its surrounding media. Remarkably, until now, there have been no quantitative and systematic studies reporting the pK(a) shifts in the common titrable amino acids upon lipid membrane insertion. Here, we applied our recently developed CpHMD-L method to calculate the pK(a) values of titrable amino acid residues incorporated in Ala-based pentapeptides at the water/membrane interface. We observed that membrane insertion leads to desolvation and a clear stabilization of the neutral forms, and we quantified the increases/decreases of the pK(a) values in the anionic/cationic residues along the membrane normal. This work highlights the importance of properly modeling the protonation equilibrium in peptides and proteins interacting with membranes using molecular dynamics simulations. PMID- 26863410 TI - Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. AB - N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ~0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprecipitation and the inherent ability of m(1)A to stall reverse transcription, as a means for transcriptome-wide m(1)A profiling. m(1)A-ID-seq identifies 901 m(1)A peaks (from 600 genes) in mRNA and noncoding RNA and reveals a prominent feature, enrichment in the 5' untranslated region of mRNA transcripts, that is distinct from the pattern for N(6)-methyladenosine, the most abundant internal mammalian mRNA modification. Moreover, m(1)A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, we show that m(1)A methylation responds dynamically to stimuli, and we identify hundreds of stress induced m(1)A sites. Collectively, our approaches allow comprehensive analysis of m(1)A modification and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m(1)A methylation. PMID- 26863411 TI - Analysis of publically available skin sensitization data from REACH registrations 2008-2014. AB - The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem's 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel's module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michaell's acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. PMID- 26863413 TI - Gold(I)-Catalyzed Cyclization/Nucleophilic Substitution of 1-(N-Sulfonylazetidin 2-yl) Ynones into N-Sulfonylpyrrolin-4-ones. AB - Polysubstituted pyrrolin-4-ones have been efficiently synthesized from readily available 1-(N-sulfonylazetidin-2-yl) ynones via gold(I)-catalyzed cyclization/nucleophilic substitution in the presence of various nucleophiles, such as water, alcohols, or indoles. Additionally, 3-iodopyrrolin-4-one derivatives have also been obtained under the same reaction conditions upon addition of 1.2 equiv of N-iodosuccinimide. PMID- 26863412 TI - Mercury Redox Chemistry in Waters of the Eastern Asian Seas: From Polluted Coast to Clean Open Ocean. AB - We performed incubation experiments using seawaters from representative marine environments of the eastern Asian seas to determine the mercury (Hg) available for photoreduction (Hgr(II)), to investigate the Hg redox reaction kinetics, and to explore the effect of environmental factors and water chemistry on the Hg redox chemistry. Results show that Hgr(II) accounted for a considerable fraction of total Hg (THg) (%Hgr(II)/THg: 24.90 +/- 10.55%, n = 27) and positively correlated with THg. Filtration decreased the Hgr(II) pool of waters with high suspended particulate matter (SPM). The positive linear relationships were found between pseudo-first order rate constants of gross Hg(II) photoreduction (kr) and gross Hg(0) photo-oxidation (ko) with photosynthetically active radiation (PAR). Under the condition of PAR of 1 m mol m(-2) s(-1), the kr were significantly (p < 0.05) lower than ko (kr/ko: 0.86 +/- 0.22). The Hg(0) dark oxidation were significantly higher than the Hg(II) dark reduction. The Hg(II) dark reduction was positively correlated to THg, and the anaerobic condition favored the Hg(II) dark reduction. Filtration significantly influenced the Hg photoredox chemistry of waters with high SPM. UVB radiation was important for both Hg(II) photoreduction and Hg(0) photo-oxidation, and the role of other wavebands in photoinduced transformations of Hg varied with the water chemistry. PMID- 26863414 TI - Dietary Variation and Evolution of Gene Copy Number among Dog Breeds. AB - Prolonged human interactions and artificial selection have influenced the genotypic and phenotypic diversity among dog breeds. Because humans and dogs occupy diverse habitats, ecological contexts have likely contributed to breed specific positive selection. Prior to the advent of modern dog-feeding practices, there was likely substantial variation in dietary landscapes among disparate dog breeds. As such, we investigated one type of genetic variant, copy number variation, in three metabolic genes: glucokinase regulatory protein (GCKR), phytanol-CoA 2-hydroxylase (PHYH), and pancreatic alpha-amylase 2B (AMY2B). These genes code for proteins that are responsible for metabolizing dietary products that originate from distinctly different food types: sugar, meat, and starch, respectively. After surveying copy number variation among dogs with diverse dietary histories, we found no correlation between diet and positive selection in either GCKR or PHYH. Although it has been previously demonstrated that dogs experienced a copy number increase in AMY2B relative to wolves during or after the dog domestication process, we demonstrate that positive selection continued to act on amylase copy number in dog breeds that consumed starch-rich diets in time periods after domestication. Furthermore, we found that introgression with wolves is not responsible for deterioration of positive selection on AMY2B among diverse dog breeds. Together, this supports the hypothesis that the amylase copy number expansion is found universally in dogs. PMID- 26863415 TI - Survival of Patients with Primary Brain Tumors: Comparison of Two Statistical Approaches. AB - PURPOSE: We reviewed the survival time for patients with primary brain tumors undergoing treatment with stereotactic radiation methods at the Masaryk Memorial Cancer Institute Brno. We also identified risk factors and characteristics, and described their influence on survival time. METHODS: In summarizing survival data, there are two functions of principal interest, namely, the survival function and the hazard function. In practice, both of them can depend on some characteristics. We focused on nonparametric methods, propose a method based on kernel smoothing, and compared our estimates with the results of the Cox regression model. The hazard function is conditional to age and gross tumor volume and visualized as a color-coded surface. A multivariate Cox model was also designed. RESULTS: There were 88 patients with primary brain cancer, treated with stereotactic radiation. The median survival of our patient cohort was 47.8 months. The estimate of the hazard function has two peaks (about 10 months and about 40 months). The survival time of patients was significantly different for various diagnoses (p?0.001), KI (p = 0.047) and stereotactic methods (p = 0.033). Patients with a greater GTV had higher risk of death. The suitable threshold for GTV is 20 cm3. Younger patients with a survival time of about 50 months had a higher risk of death. In the multivariate Cox regression model, the selected variables were age, GTV, sex, diagnosis, KI, location, and some of their interactions. CONCLUSION: Kernel methods give us the possibility to evaluate continuous risk variables and based on the results offer risk-prone patients a different treatment, and can be useful for verifying assumptions of the Cox model or for finding thresholds of continuous variables. PMID- 26863416 TI - Collective Decision-Making in Homing Pigeons: Larger Flocks Take Longer to Decide but Do Not Make Better Decisions. AB - Social animals routinely are challenged to make consensus decisions about movement directions and routes. However, the underlying mechanisms facilitating such decision-making processes are still poorly known. A prominent question is how group members participate in group decisions. We addressed this question by examining how flocks of homing pigeons (Columba livia) decide their homing direction. We released newly formed flocks varying in size and determined the time taken to choose a homing direction (decision-making period) and the accuracy of that choice. We found that the decision-making period increases exponentially with flock size, which is consistent with a participatory decision-making process. We additionally found that there is no effect of flock size on the accuracy of the decisions made, which does not match with current theory for democratic choices of flight directions. Our combined results are better explained by a participatory choice of leaders that subsequently undertake the flock directional decisions. However, this decision-making model would only entirely fit with our results if leaders were chosen based on traits other than their navigational experience. Our study provides rare empirical evidence elucidating decision-making processes in freely moving groups of animals. PMID- 26863417 TI - The Impact of the Choice of Data Source in Record Linkage Studies Estimating Mortality in Venous Thromboembolism. AB - Linked electronic healthcare databases are increasingly being used in observational research. The objective of this study was to investigate the impact of the choice of data source in estimating mortality following VTE, with a secondary aim to investigate the influence of the denominator definition. We used the UK Clinical Practice Research Datalink (CPRD) to identify patients aged 18+ with venous thromboembolism (VTE). Multiple cohorts were identified in order to assess how mortality rates differed with a range of data sources. For each of the cohorts, incidence rates per 1,000 person years (/1000py) and relative rates (RRs) of all-cause mortality were calculated. The lowest mortality rate was found when only primary care data were used for both the exposure (VTE) and the outcome (death) (108.4/1000py). The highest mortality rate was found for patients diagnosed in secondary care (237.2/1000py). When linked primary and secondary care data were included for eligible patients and for the overlapping period of data collection, a mortality rate of 173.2/1000py was found. Sensitivity analyses varying the denominator definition provided a range of results (140.6 164.3/1000py). The relative rates of mortality by gender and age were comparable across all cohorts. Depending on the choice of data source, the population studied may be different. This may have substantial impact on the main findings, in particular on incidence rates of mortality following VTE. PMID- 26863418 TI - Hydrophobic Interactions Are a Key to MDM2 Inhibition by Polyphenols as Revealed by Molecular Dynamics Simulations and MM/PBSA Free Energy Calculations. AB - p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy) have major contribution in binding free energy. PMID- 26863419 TI - Low Cardiac Output Leads Hepatic Fibrosis in Right Heart Failure Model Rats. AB - BACKGROUND: Hepatic fibrosis progresses with right heart failure, and becomes cardiac cirrhosis in a severe case. Although its causal factor still remains unclear. Here we evaluated the progression of hepatic fibrosis using a pulmonary artery banding (PAB)-induced right heart failure model and investigated whether cardiac output (CO) is responsible for the progression of hepatic fibrosis. METHODS AND RESULTS: Five-week-old Sprague-Dawley rats divided into the PAB and sham-operated control groups. After 4 weeks from operation, we measured CO by echocardiography, and hepatic fibrosis ratio by pathological examination using a color analyzer. In the PAB group, CO was significantly lower by 48% than that in the control group (78.2+/-27.6 and 150.1+/-31.2 ml/min, P<0.01). Hepatic fibrosis ratio and serum hyaluronic acid, an index of hepatic fibrosis, were significantly increased in the PAB group than those in the control group (7.8+/-1.7 and 1.0+/ 0.2%, P<0.01, 76.2+/-27.5 and 32.7+/-7.5 ng/ml, P<0.01). Notably, the degree of hepatic fibrosis significantly correlated a decrease in CO. Immunohistological analysis revealed that hepatic stellate cells were markedly activated in hypoxic areas, and HIF-1alpha positive hepatic cells were increased in the PAB group. Furthermore, by real-time PCR analyses, transcripts of profibrotic and fibrotic factors (TGF-beta1, CTGF, procollargen I, procollargen III, MMP 2, MMP 9, TIMP 1, TIMP 2) were significantly increased in the PAB group. In addition, western blot analyses revealed that the protein level of HIF-1alpha was significantly increased in the PAB group than that in the control group (2.31+/-0.84 and 1.0+/ 0.18 arbitrary units, P<0.05). CONCLUSIONS: Our study demonstrated that low CO and tissue hypoxia were responsible for hepatic fibrosis in right failure heart model rats. PMID- 26863420 TI - Music for a Brighter World: Brightness Judgment Bias by Musical Emotion. AB - A prevalent conceptual metaphor is the association of the concepts of good and evil with brightness and darkness, respectively. Music cognition, like metaphor, is possibly embodied, yet no study has addressed the question whether musical emotion can modulate brightness judgment in a metaphor consistent fashion. In three separate experiments, participants judged the brightness of a grey square that was presented after a short excerpt of emotional music. The results of Experiment 1 showed that short musical excerpts are effective emotional primes that cross-modally influence brightness judgment of visual stimuli. Grey squares were consistently judged as brighter after listening to music with a positive valence, as compared to music with a negative valence. The results of Experiment 2 revealed that the bias in brightness judgment does not require an active evaluation of the emotional content of the music. By applying a different experimental procedure in Experiment 3, we showed that this brightness judgment bias is indeed a robust effect. Altogether, our findings demonstrate a powerful role of musical emotion in biasing brightness judgment and that this bias is aligned with the metaphor viewpoint. PMID- 26863421 TI - Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report. AB - The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results. PMID- 26863422 TI - Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves' Hyperthyroidism. AB - Genotyping increases the accuracy of a clinical score (based on pretreatment age, goiter size, FT4, TBII) for predicting recurrence of Graves' hyperthyroidism after a course of antithyroid drugs: a prospective study. PMID- 26863424 TI - Circulating Retinoic Acid Levels and the Development of Metabolic Syndrome. AB - CONTEXT AND OBJECTIVE: In this prospective study, we evaluated the association of retinoic acid (RA) with the metabolic syndrome (MetS) in the Chinese population. DESIGN AND PARTICIPANTS: A total of 1042 nondiabetic adults from the population based Nutrition and Health of Aging Population were prospectively followed up for 4 years. Serum RA concentrations was determined and its relationship with the MetS and its component was investigated. RESULTS: At baseline, higher RA levels were inversely associated with the presence of MetS (odds ratio 0.61; 95% confidence interval [CI] 0.44-0.74, P < .001) after adjustment for age, gender, body mass index, the homeostasis model assessment index for insulin resistance (HOMA-IR), and other confounding factors. Subjects with lower RA levels had a progressively worse cardiometabolic risk profile at baseline. Serum RA levels were inversely associated with 8-iso-prostaglandin F2alpha (P < .001), high sensitivity C-reactive protein (P = .015), and IL-6 (P = .020) and positively correlated with high-density lipoprotein cholesterol (P = .038). Among 825 subjects without MetS at baseline, 146 had developed it at 4 years. Serum RA by quartiles was inversely correlated with the incident MetS (adjusted hazard ratio 0.67; 95% CI 0.48-0.81, P = .006). Apart from HOMA-IR (P < .001), the baseline RA level was the only independent predictor of the development of the MetS during the 4-year follow-up (odds ratio 0.53; 95% CI 0.40-0.69; P < .001) after adjustment for age, gender, body mass index, and HOMA-IR. CONCLUSIONS: The serum RA level is inversely associated with the development of MetS independently of adiposity and insulin resistance. PMID- 26863423 TI - Sodium Intake and Osteoporosis. Findings From the Women's Health Initiative. AB - In this large, prospective, observational cohort study of postmenopausal women in the WHI, Cox proportional hazard regression models showed that sodium intake at or near recommended levels is not likely to impact bone metabolism. PMID- 26863425 TI - Obesity, Metabolic Health, and History of Cytomegalovirus Infection in the General Population. AB - CONTEXT: Common community-acquired infections such as cytomegalovirus (CMV), may contribute to the development of obesity and metabolic dysfunction, but empirical evidence is scarce. OBJECTIVE: We examined the associations between CMV, obesity, and metabolic characteristics in a large, general population-based sample of adults. DESIGN AND SETTING, PARTICIPANTS: This was an observational study in community dwelling adults from the general population, Understanding Society-the UK Household Longitudinal Study composed on 9517 men and women (age 52.4 +/- 16.4 y; 55.3% female). MEASURES: CMV infection was measured IgG from serum. Obesity was defined as body mass index >=30 kg/m2. Based on blood pressure, high-density lipoprotein cholesterol, triglycerides, glycated hemoglobin A1c, and C-reactive protein, participants were classified as either Healthy (0 or 1 metabolic abnormality) or Unhealthy (>=2 metabolic abnormalities). RESULTS: A positive CMV test was recorded in 47.5% of the sample. There was no association between CMV and obesity. Of the individual metabolic risk factors, CMV was positively associated with glycated hemoglobin and high-density lipoprotein cholesterol. In combination, only Unhealthy Nonobese participants had modestly increased odds of CMV (odds ratio compared with healthy normal-weight, 1.12; 95% confidence interval, 1.00-1.26) after adjusting for a range of variables. CMV was associated with an increased prevalence of cardiovascular diseases (odds ratio, 1.67; 95% CI, 1.07-2.60) independently of obesity, metabolic risk factors, and other covariates. CONCLUSION: Our findings suggest a weak but statistically significant association between CMV and metabolic dysfunction in nonobese adults. This relationship seems to be masked in the obese, possibly by the effects of excess adiposity on metabolism. PMID- 26863426 TI - C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico. AB - BACKGROUND: Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. METHODS: Anthropometrics, glucose, insulin, C peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C peptide. Correlations were calculated using the Spearman correlation coefficient (rho). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. RESULTS: Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. CONCLUSION: C-peptide is a strong indicator of MetS. Since C peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS. PMID- 26863427 TI - Epimerase and Reductase Activities of Polyketide Synthase Ketoreductase Domains Utilize the Same Conserved Tyrosine and Serine Residues. AB - The role of the conserved active site tyrosine and serine residues in epimerization catalyzed by polyketide synthase ketoreductase (PKS KR) domains has been investigated. Both mutant and wild-type forms of epimerase-active KR domains, including the intrinsically redox-inactive EryKR3 degrees and PicKR3 degrees as well as redox-inactive mutants of EryKR1, were incubated with [2 (2)H]-(2R,3S)-2-methyl-3-hydroxypentanoyl-SACP ([2-(2)H]-2) and 0.05 equiv of NADP(+) in the presence of the redox-active, epimerase-inactive EryKR6 domain. The residual epimerase activity of each mutant was determined by tandem equilibrium isotope exchange, in which the first-order, time-dependent washout of isotope from 2 was monitored by liquid chromatography-tandem mass spectrometry with quantitation of the deuterium content of the diagnostic pantetheinate ejection fragment (4). Replacement of the active site Tyr or Ser residues, alone or together, significantly reduced the observed epimerase activity of each KR domain with minimal effect on substrate binding. Our results demonstrate that the epimerase and reductase activities of PKS KR domains share a common active site, with both reactions utilizing the same pair of Tyr and Ser residues. PMID- 26863428 TI - Estimating the Relative Role of Various Subcategories of Food, Water, and Animal Contact Transmission of 28 Enteric Diseases in Canada. AB - OBJECTIVE: Enteric illness represents a significant burden of illness in Canada and internationally. Building on previous research, an expert elicitation was undertaken to explore the routes of transmission for 28 pathogens involved in enteric illness in Canada. This article considers the subcategories of foodborne, waterborne, and animal contact transmission. METHODS: As part of an expert elicitation, 31 experts were asked to provide estimates of source attribution for subcategories of foodborne (n = 15), waterborne (n = 10), and animal contact (n = 3) transmission. The results from an online survey were combined using triangular probability distributions, and median and 90% credible intervals were produced. The total proportion and estimated number of cases of enteric illness attributable to each type of food commodity, water source, and animal exposure route were calculated using results from the larger elicitation survey and from a recent Canadian foodborne burden of illness study (Thomas et al., 2013). RESULTS: Thirty experts provided foodborne subcategory estimates for 15/28 pathogens, waterborne subcategory estimates for 14/28 pathogens and animal contact subcategory estimates for 5/28. The elicitation identified raw produce, recreational water, and farm animal contact as important risk factors for enteric illness. These results also highlighted the complexity of transmission, with greater uncertainty for certain pathogens and routes of transmission. CONCLUSIONS: This study is the first of its kind to explore subcategories of foodborne, waterborne, and animal contact transmission across such a range of enteric pathogens. Despite inherent uncertainty, these estimates present an important quantitative synthesis of the roles of foodborne commodities, water sources, and pathways of animal contact in the transmission of enteric illness in Canada. PMID- 26863429 TI - Systemic Analysis of Foodborne Disease Outbreak in Korea. AB - This study systemically analyzed data on the prevalence of foodborne pathogens and foodborne disease outbreaks to identify the priorities of foodborne infection risk management in Korea. Multiple correspondence analysis was applied to three variables: origin of food source, phase of food supply chain, and 12 pathogens using 358 cases from 76 original papers and official reports published in 1998 2012. In addition, correspondence analysis of two variables--place and pathogen- was conducted based on epidemiological data of 2357 foodborne outbreaks in 2002 2011 provided by the Korean Ministry of Food and Drug Safety. The results of this study revealed three distinct areas of food monitoring: (1) livestock-derived raw food contaminated with Campylobacter spp., pathogenic Escherichia coli, Salmonella spp., and Listeria monocytogenes; (2) multi-ingredient and ready-to eat food related to Staphylococcus aureus; and (3) water associated with norovirus. Our findings emphasize the need to track the sources and contamination pathways of foodborne pathogens for more effective risk management. PMID- 26863430 TI - Novel SLC19A3 Promoter Deletion and Allelic Silencing in Biotin-Thiamine Responsive Basal Ganglia Encephalopathy. AB - BACKGROUND: Biotin-thiamine responsive basal ganglia disease is a severe, but potentially treatable disorder caused by mutations in the SLC19A3 gene. Although the disease is inherited in an autosomal recessive manner, patients with typical phenotypes carrying single heterozygous mutations have been reported. This makes the diagnosis uncertain and may delay treatment. METHODS AND RESULTS: In two siblings with early-onset encephalopathy dystonia and epilepsy, whole-exome sequencing revealed a novel single heterozygous SLC19A3 mutation (c.337T>C). Although Sanger-sequencing and copy-number analysis revealed no other aberrations, RNA-sequencing in brain tissue suggested the second allele was silenced. Whole-genome sequencing resolved the genetic defect by revealing a novel 45,049 bp deletion in the 5'-UTR region of the gene abolishing the promoter. High dose thiamine and biotin therapy was started in the surviving sibling who remains stable. In another patient two novel compound heterozygous SLC19A3 mutations were found. He improved substantially on thiamine and biotin therapy. CONCLUSIONS: We show that large genomic deletions occur in the regulatory region of SLC19A3 and should be considered in genetic testing. Moreover, our study highlights the power of whole-genome sequencing as a diagnostic tool for rare genetic disorders across a wide spectrum of mutations including non-coding large genomic rearrangements. PMID- 26863431 TI - Azidobupramine, an Antidepressant-Derived Bifunctional Neurotransmitter Transporter Ligand Allowing Covalent Labeling and Attachment of Fluorophores. AB - The aim of this study was to design, synthesize and validate a multifunctional antidepressant probe that is modified at two distinct positions. The purpose of these modifications was to allow covalent linkage of the probe to interaction partners, and decoration of probe-target complexes with fluorescent reporter molecules. The strategy for the design of such a probe (i.e., azidobupramine) was guided by the need for the introduction of additional functional groups, conveying the required properties while keeping the additional moieties as small as possible. This should minimize the risk of changing antidepressant-like properties of the new probe azidobupramine. To control for this, we evaluated the binding parameters of azidobupramine to known target sites such as the transporters for serotonin (SERT), norepinephrine (NET), and dopamine (DAT). The binding affinities of azidobupramine to SERT, NET, and DAT were in the range of structurally related and clinically active antidepressants. Furthermore, we successfully visualized azidobupramine-SERT complexes not only in SERT-enriched protein material but also in living cells stably overexpressing SERT. To our knowledge, azidobupramine is the first structural analogue of a tricyclic antidepressant that can be covalently linked to target structures and further attached to reporter molecules while preserving antidepressant-like properties and avoiding radioactive isotopes. PMID- 26863432 TI - In Vivo Validation of Simultaneous Non-Contrast Angiography and intraPlaque Hemorrhage (SNAP) Magnetic Resonance Angiography: An Intracranial Artery Study. AB - OBJECTIVES: Simultaneous Non-contrast Angiography and intraPlaque hemorrhage (SNAP) technique was recently proposed for joint MRA and intraplaque hemorrhage (IPH) imaging. The purpose of this study is to validate SNAP's MRA performance in patients with suspected intracranial artery disease. METHODS: SNAP and time-of flight (TOF) techniques with matched field of view and resolution were applied on 15 patients with suspected intracranial artery disease. Both techniques were evaluated based on their detection of luminal stenosis of bilateral middle cerebral arteries (MCA) and the delineation of smallest visible branches (SVB) of the MCA. Statistical analysis was conducted on the artery level. RESULTS: The SNAP MRA was found to provide similar stenosis detection performance when compared with TOF (Cohen's kappa 0.79; 95% Confidence Interval: 0.56-0.99). For the SVB comparison, SNAP was found to provide significantly better small artery delineation than TOF (p = 0.017). Inter-reader reproducibility for both measurements on SNAP was over 0.7. SNAP also detected IPH lesions on 13% of the patients. CONCLUSIONS: The SNAP technique's MRA performance was optimized and compared against TOF for intracranial artery atherosclerosis imaging and was found to provide comparable stenosis detection accuracy. Along with its IPH detection capability, SNAP holds the potential to become a first-line screening tool for high risk intracranial atherosclerosis disease evaluation. PMID- 26863433 TI - UK National Survey of Practice Patterns of Fluid Volume Management in Haemodialysis Patients: A Need for Evidence. AB - BACKGROUND: Fluid management in haemodialysis (HD) affects patient experience, morbidity and mortality. Standards for best practice are lacking. A national survey of the United Kingdom was undertaken to define prevalent practice. METHODS: An online questionnaire was distributed to all UK renal centres. RESULTS: Forty-five of 74 centres (173 dialysis units), serving 62% (n = 14,697) of UK HD population responded. Seventy-eight per cent had no agreed policy for managing fluid balance in patients on HD; 44% did not assess fluid status routinely. Clinical assessment was the norm; 27% used bio-impedance-based device. To achieve a target-weight, 53% reduced weight as far as tolerated. Twenty-two per cent measured residual renal function (RRF). Ninety-one per cent had no policy for fluid overload. Sixty-four per cent restricted salt and water. Ninety three per cent used diuretics in patients with RRF. Thirty-eight per cent felt management was adequate; 77% felt there was a need for better evidence. Ninety one per cent would participate in a study addressing this. CONCLUSION: There is an urgent need for establishing an evidence base on the optimal approaches to fluid management. PMID- 26863434 TI - Inter-Individual Differences in RNA Levels in Human Peripheral Blood. AB - Relatively little is known about the range of RNA levels in human blood. This report provides assessment of peripheral blood RNA level and its inter-individual differences in a group of 35 healthy humans consisting of 25 females and 10 males ranging in age from 50 to 89 years. In this group, the average total RNA level was 14.59 MUg/ml of blood, with no statistically significant difference between females and males. The individual RNA level ranged from 6.7 to 22.7 MUg/ml of blood. In healthy subjects, the repeated sampling of an individual's blood showed that RNA level, whether high or low, was stable. The inter-individual differences in RNA level in blood can be attributed to both, differences in cell number and the amount of RNA per cell. The 3.4-fold range of inter-individual differences in total RNA levels, documented herein, should be taken into account when evaluating the results of quantitative RT-PCR and/or RNA sequencing studies of human blood. Based on the presented results, a comprehensive assessment of gene expression in blood should involve determination of both the amount of mRNA per unit of total RNA (U / ng RNA) and the amount of mRNA per unit of blood (U / ml blood) to assure a thorough interpretation of physiological or pathological relevance of study results. PMID- 26863435 TI - Correction: Selenium Supplementation in Fish: A Combined Chemical and Biomolecular Study to Understand Sel-Plex Assimilation and Impact on Selenoproteome Expression in Rainbow Trout (Oncorhynchus mykiss). PMID- 26863436 TI - An Orally Active Allosteric GLP-1 Receptor Agonist Is Neuroprotective in Cellular and Rodent Models of Stroke. AB - Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor. The aim of this study was to evaluate the neuroprotective effects of DMB on transient focal cerebral ischemia. In cultured cortical neurons, DMB activated the GLP-1R, leading to increased intracellular cAMP levels with an EC50 value about 100 fold that of exendin-4. Pretreatment of neurons with DMB protected against necrotic and apoptotic cell death was induced by oxygen-glucose deprivation (OGD). The neuroprotective effects of DMB were blocked by GLP-1R knockdown with shRNA but not by GLP-1R antagonism. In C57BL/6 mice, DMB was orally administered 30 min prior to middle cerebral artery occlusion (MCAO) surgery. DMB markedly reduced the cerebral infarct size and neurological deficits caused by MCAO and reperfusion. The neuroprotective effects were mediated by activation of the GLP-1R through the cAMP-PKA-CREB signaling pathway. DMB exhibited anti-apoptotic effects by modulating Bcl-2 family members. These results provide evidence that DMB, a small molecular GLP-1R agonist, attenuates transient focal cerebral ischemia injury and inhibits neuronal apoptosis induced by MCAO. Taken together, these data suggest that DMB is a potential neuroprotective agent against cerebral ischemia. PMID- 26863437 TI - Song Perception by Professional Singers and Actors: An MEG Study. AB - The cortical correlates of speech and music perception are essentially overlapping, and the specific effects of different types of training on these networks remain unknown. We compared two groups of vocally trained professionals for music and speech, singers and actors, using recited and sung rhyme sequences from German art songs with semantic and/ or prosodic/melodic violations (i.e. violations of pitch) of the last word, in order to measure the evoked activation in a magnetoencephalographic (MEG) experiment. MEG data confirmed the existence of intertwined networks for the sung and spoken modality in an early time window after word violation. In essence for this early response, higher activity was measured after melodic/prosodic than semantic violations in predominantly right temporal areas. For singers as well as for actors, modality-specific effects were evident in predominantly left-temporal lateralized activity after semantic expectancy violations in the spoken modality, and right-dominant temporal activity in response to melodic violations in the sung modality. As an indication of a special group-dependent audiation process, higher neuronal activity for singers appeared in a late time window in right temporal and left parietal areas, both after the recited and the sung sequences. PMID- 26863438 TI - Colony Failure Linked to Low Sperm Viability in Honey Bee (Apis mellifera) Queens and an Exploration of Potential Causative Factors. AB - Queen health is closely linked to colony performance in honey bees as a single queen is normally responsible for all egg laying and brood production within the colony. In the U. S. in recent years, queens have been failing at a high rate; with 50% or greater of queens replaced in colonies within 6 months when historically a queen might live one to two years. This high rate of queen failure coincides with the high mortality rates of colonies in the US, some years with >50% of colonies dying. In the current study, surveys of sperm viability in US queens were made to determine if sperm viability plays a role in queen or colony failure. Wide variation was observed in sperm viability from four sets of queens removed from colonies that beekeepers rated as in good health (n = 12; average viability = 92%), were replacing as part of normal management (n = 28; 57%), or where rated as failing (n = 18 and 19; 54% and 55%). Two additional paired set of queens showed a statistically significant difference in viability between colonies rated by the beekeeper as failing or in good health from the same apiaries. Queens removed from colonies rated in good health averaged high viability (ca. 85%) while those rated as failing or in poor health had significantly lower viability (ca. 50%). Thus low sperm viability was indicative of, or linked to, colony performance. To explore the source of low sperm viability, six commercial queen breeders were surveyed and wide variation in viability (range 60-90%) was documented between breeders. This variability could originate from the drones the queens mate with or temperature extremes that queens are exposed to during shipment. The role of shipping temperature as a possible explanation for low sperm viability was explored. We documented that during shipment queens are exposed to temperature spikes (<8 and > 40 degrees C) and these spikes can kill 50% or more of the sperm stored in queen spermathecae in live queens. Clearly low sperm viability is linked to colony performance and laboratory and field data provide evidence that temperature extremes are a potential causative factor. PMID- 26863439 TI - The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites. AB - Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication. PMID- 26863441 TI - Correction: Overexpression of MEOX2 and TWIST1 is Associated with H3K27me3 Levels and Determines Lung Cancer Chemoresistance and Prognosis. PMID- 26863440 TI - In Vitro Study of Taenia solium Postoncospheral Form. AB - BACKGROUND: The transitional period between the oncosphere and the cysticercus of Taenia solium is the postoncospheral (PO) form, which has not yet been completely characterized. The aim of this work was to standardize a method to obtain T. solium PO forms by in vitro cultivation. We studied the morphology of the PO form and compared the expression of antigenic proteins among the PO form, oncosphere, and cysticerci stages. METHODOLOGY/PRINCIPAL FINDINGS: T. solium activated oncospheres were co-cultured with ten cell lines to obtain PO forms, which we studied at three stages of development--days 15, 30, and 60. A high percentage (32%) of PO forms was obtained using HCT-8 cells in comparison to the other cell lines. The morphology was observed by bright field, scanning, and transmission electron microscopy. Morphology of the PO form changed over time, with the six hooks commonly seen in the oncosphere stage disappearing in the PO forms, and vesicles and microtriches observed in the tegument. The PO forms grew as they aged, reaching a diameter of 2.5 mm at 60 days of culture. 15-30 day PO forms developed into mature cysticerci when inoculated into rats. Antigenic proteins expressed in the PO forms are also expressed by the oncosphere and cysticerci stages, with more cysticerci antigenic proteins expressed as the PO forms ages. CONCLUSIONS/SIGNIFICANCE: This is the first report of an in vitro production method of T. solium PO forms. The changes observed in protein expression may be useful in identifying new targets for vaccine development. In vitro culture of PO form will aid in understanding the host-parasite relationship, since the structural changes of the developing PO forms may reflect the parasite's immunoprotective mechanisms. A wider application of this method could significantly reduce the use of animals, and thus the costs and time required for further experimental investigations. PMID- 26863442 TI - Expectancy of ergogenicity from sodium bicarbonate ingestion increases high intensity cycling capacity. AB - This study examined whether expectancy of ergogenicity of a commonly used nutritional supplement (sodium bicarbonate; NaHCO3) influenced subsequent high intensity cycling capacity. Eight recreationally active males (age, 21 +/- 1 years; body mass, 75 +/- 8 kg; height, 178 +/- 4 cm; WPEAK = 205 +/- 22 W) performed a graded incremental test to assess peak power output (WPEAK), one familiarisation trial and two experimental trials. Experimental trials consisted of cycling at 100% WPEAK to volitional exhaustion (TLIM) 60 min after ingesting either a placebo (PLA: 0.1 g.kg(-1) sodium chloride (NaCl), 4 mL.kg(-1) tap water, and 1 mL.kg(-1) squash) or a sham placebo (SHAM: 0.1 g.kg(-1) NaCl, 4 mL.kg(-1) carbonated water, and 1 mL.kg(-1) squash). SHAM aimed to replicate the previously reported symptoms of gut fullness (GF) and abdominal discomfort (AD) associated with NaHCO3 ingestion. Treatments were administered double blind and accompanied by written scripts designed to remain neutral (PLA) or induce expectancy of ergogenicity (SHAM). After SHAM mean TLIM increased by 9.5% compared to PLA (461 +/- 148 s versus 421 +/- 150 s; P = 0.048, d = 0.3). Ratings of GF and AD were mild but ~1 unit higher post-ingestion for SHAM. After 3 min TLIM overall ratings of perceived exertion were 1.4 +/- 1.3 units lower for SHAM compared to PLA (P = 0.020, d = 0.6). There were no differences between treatments for blood lactate, blood glucose, or heart rate. In summary, ergogenicity after NaHCO3 ingestion may be influenced by expectancy, which mediates perception of effort during subsequent exercise. The observed ergogenicity with SHAM did not affect our measures of cardiorespiratory physiology or metabolic flux. PMID- 26863444 TI - Overexpression of the CYP51A1 Gene and Repeated Elements are Associated with Differential Sensitivity to DMI Fungicides in Venturia inaequalis. AB - The involvement of overexpression of the CYP51A1 gene in Venturia inaequalis was investigated for isolates exhibiting differential sensitivity to the triazole demethylation inhibitor (DMI) fungicides myclobutanil and difenoconazole. Relative expression (RE) of the CYP51A1 gene was significantly greater (P < 0.0001) for isolates with resistance to both fungicides (MRDR phenotype) or with resistance to difenoconazole only (MSDR phenotype) compared with isolates that were resistant only to myclobutanil (MRDS phenotype) or sensitive to both fungicides (MSDS phenotype). An average of 9- and 13-fold increases in CYP51A1 RE were observed in isolates resistant to difenoconazole compared with isolates with MRDS and MSDS phenotypes, respectively. Linear regression analysis between isolate relative growth on myclobutanil-amended medium and log10 RE revealed that little to no variability in sensitivity to myclobutanil could be explained by CYP51A1 overexpression (R(2) = 0.078). To investigate CYP51A1 upstream anomalies associated with CYP51A1 overexpression or resistance to difenoconazole, Illumina sequencing was conducted for three isolates with resistance to difenoconazole and one baseline isolate. A repeated element, "EL 3,1,2", with the properties of a transcriptional enhancer was identified two to four times upstream of CYP51A1 in difenoconazole-resistant isolates but was not found in isolates with the MRDS phenotype. These results suggest that different mechanisms may govern resistance to different DMI fungicides in the triazole group. PMID- 26863443 TI - National Economic Development Status May Affect the Association between Central Adiposity and Cognition in Older Adults. AB - BACKGROUND: Obesity is becoming a global problem, rather than one found only in developed countries. Although recent studies have suggested a detrimental effect of obesity on cognition, studies of the relationship between obesity and cognition among older adults have been limited to developed countries. We aimed to examine the associations between central obesity, as measured by waist circumference, and cognition level in adults aged 50 years and older in England and Indonesia. METHODS: We used linear regression models to analyse these associations and multiple imputation to manage missing data. The 2006 English Longitudinal Study of Ageing Wave 3 is the source of data from England, while data from Indonesia is sourced from the 2007 Indonesian Family Life Survey Wave 4. FINDINGS: Centrally obese respondents had lower cognition levels than non centrally obese respondents in England. In contrast, central adiposity had a statistically significant positive association with cognition in Indonesia. Higher levels of education and higher economic status were associated with higher cognitive ability, while age was associated with lower cognition in both countries. Elevated C-reactive protein (CRP) concentrations and smoking behaviour, both linked to higher risk of obesity, were negatively associated with cognitive ability among older adults in England, but they had no statistically significant association with cognition among Indonesians. INTERPRETATION: The contradictory findings on obesity and cognition in England and Indonesia not only create a puzzle, but they may also have different policy implications in these countries. Reducing the prevalence of obesity may be the main focus in England and other developed countries to maintain older adults' cognition. However, Indonesia and other developing countries should place more emphasis on education, in addition to continued efforts to tackle the double burden of malnutrition, in order to prevent cognitive impairment among older adults. PMID- 26863445 TI - Microbial Communities in Globodera pallida Females Raised in Potato Monoculture Soil. AB - Globodera spp. are under strict quarantine in many countries. Suppressiveness to cyst nematodes can evolve under monoculture of susceptible hosts. Females developing in potato monoculture soil infested with G. pallida populations Chavornay or Delmsen were examined for inherent microbial communities. In the greenhouse, nonheated and heat-treated (134 degrees C for 10 min) portions of this soil were placed in root observation chambers, planted with Solanum tuberosum 'Selma', and inoculated with G. pallida Pa3 Chavornay. At harvest in Delmsen soil, cysts had fewer eggs in nonheated than heat-treated soil. In denaturing gradient gel electrophoresis analysis, bacterial and fungal fingerprints were characterized by a high variability between replicates; nonheated soils displayed more dominant bands than heated soils, indicating more bacterial and fungal populations. In amplicon pyrosequencing, females from nonheated portions frequently contained internal transcribed spacer sequences of the fungus Malassezia. Specific for the Chavornay and Delmsen population, ribosomal sequences of the bacteria Burkolderia and Ralstonia were abundant on eggs. In this first report of microbial communities in G. pallida raised in potato monoculture, candidate microorganisms perhaps associated with the health status of the eggs of G. pallida were identified. If pathologies on cyst nematodes can be ascertained, these organisms could improve the sustainability of production systems. PMID- 26863446 TI - HER3 expression is correlated to distally located and low-grade colon cancer. AB - Background HER3 is a member of the human epidermal growth factor receptor complex (EGFR, HER2, HER3 and HER4). It has been investigated as a prognostic biomarker in colorectal cancer but is sparingly studied in colon cancer. HER3 can affect cellular proliferation, differentiation and migration in oncogenesis through ligand binding and activation of intracellular signal pathways. Recently, we found that expression of cell surface HER3 can be detected at a high extent in primary colorectal tumors, lymph node and liver metastases and that it correlated with poor prognosis. This large, explorative, retrospective study evaluates the prognostic value of HER3 in colon cancer and the association of HER3 to tumor location. MATERIAL AND METHODS: Immunohistochemical detection with a monoclonal HER3 antibody in primary colon tumors of stage II and III, from 521 patients, was performed. Results HER3 was expressed at high levels in 67% of the colon tumors. High HER3 expression was associated with distal tumor location (p < 0.0001) and low-grade tumor (p < 0.0001). In the group of patients with distal colon cancer (230/521), HER3 expression correlated to shorter disease-free survival (DFS) (p = 0.03) in the univariate analysis and in the multivariate analysis, a hazard ratio of 0.56 (95% CI 0.31-0.99) (p = 0.047) was observed. Conclusion In this explorative, retrospective study, high HER3 expression in colon cancer was associated to distal colon location and low-grade tumor. High HER3 expression was of prognostic value according to DFS in distal colon cancer in univariate and multivariate analysis. We could not find a significant value of HER3 expression with respect to overall survival (OS). PMID- 26863447 TI - Calcium Imaging of Neuronal Activity in Drosophila Can Identify Anticonvulsive Compounds. AB - Although there are now a number of antiepileptic drugs (AEDs) available, approximately one-third of epilepsy patients respond poorly to drug intervention. The reasons for this are complex, but are probably reflective of the increasing number of identified mutations that predispose individuals to this disease. Thus, there is a clear requirement for the development of novel treatments to address this unmet clinical need. The existence of gene mutations that mimic a seizure like behaviour in the fruit fly, Drosophila melanogaster, offers the possibility to exploit the powerful genetics of this insect to identify novel cellular targets to facilitate design of more effective AEDs. In this study we use neuronal expression of GCaMP, a potent calcium reporter, to image neuronal activity using a non-invasive and rapid method. Expression in motoneurons in the isolated CNS of third instar larvae shows waves of calcium-activity that pass between segments of the ventral nerve cord. Time between calcium peaks, in the same neurons, between adjacent segments usually show a temporal separation of greater than 200 ms. Exposure to proconvulsants (picrotoxin or 4-aminopyridine) reduces separation to below 200 ms showing increased synchrony of activity across adjacent segments. Increased synchrony, characteristic of epilepsy, is similarly observed in genetic seizure mutants: bangsenseless1 (bss1) and paralyticK1270T (paraK1270T). Exposure of bss1 to clinically-used antiepileptic drugs (phenytoin or gabapentin) significantly reduces synchrony. In this study we use the measure of synchronicity to evaluate the effectiveness of known and novel anticonvulsive compounds (antipain, isethionate, etopiside rapamycin and dipyramidole) to reduce seizure-like CNS activity. We further show that such compounds also reduce the Drosophila voltage-gated persistent Na+ current (INaP) in an identified motoneuron (aCC). Our combined assays provide a rapid and reliable method to screen unknown compounds for potential to function as anticonvulsants. PMID- 26863448 TI - The effects of motor rehabilitation training on clinical symptoms and serum BDNF levels in Parkinson's disease subjects. AB - Increasing evidence suggests that motor rehabilitation may delay Parkinson's disease (PD) progression. Moreover, parallel treatments in animals up-regulate brain-derived neurotrophic factor (BDNF). Thus, we investigated the effect of a motor rehabilitation protocol on PD symptoms and BDNF serum levels. Motor rehabilitation training consisted of a cycle of 20 days/month of physiotherapy divided in 3 daily sessions. Clinical data were collected at the beginning, at the end, and at 90 days follow-up. BDNF serum levels were detected by ELISA at 0, 7, 14, 21, 30, and 90 days. The follow-up period had a duration of 60 days (T30 T90). The results showed that at the end of the treatment (day 30), an improvement in extrapyramidal signs (UPDRS III; UPDRS III - Gait and Balance items), motor (6 Minute Walking Test), and daily living activities (UPDRS II; PDQ 39) was observed. BDNF levels were increased at day 7 as compared with baseline. After that, no changes in BDNF were observed during the treatment and in the successive follow-up. This study demonstrates that motor rehabilitation training is able to ameliorate PD symptoms and to increase temporarily BDNF serum levels. The latter effect may potentially contribute to the therapeutic action. PMID- 26863449 TI - Advanced Experimental Methods for Low-temperature Magnetotransport Measurement of Novel Materials. AB - Novel electronic materials are often produced for the first time by synthesis processes that yield bulk crystals (in contrast to single crystal thin film synthesis) for the purpose of exploratory materials research. Certain materials pose a challenge wherein the traditional bulk Hall bar device fabrication method is insufficient to produce a measureable device for sample transport measurement, principally because the single crystal size is too small to attach wire leads to the sample in a Hall bar configuration. This can be, for example, because the first batch of a new material synthesized yields very small single crystals or because flakes of samples of one to very few monolayers are desired. In order to enable rapid characterization of materials that may be carried out in parallel with improvements to their growth methodology, a method of device fabrication for very small samples has been devised to permit the characterization of novel materials as soon as a preliminary batch has been produced. A slight variation of this methodology is applicable to producing devices using exfoliated samples of two-dimensional materials such as graphene, hexagonal boron nitride (hBN), and transition metal dichalcogenides (TMDs), as well as multilayer heterostructures of such materials. Here we present detailed protocols for the experimental device fabrication of fragments and flakes of novel materials with micron-sized dimensions onto substrate and subsequent measurement in a commercial superconducting magnet, dry helium close-cycle cryostat magnetotransport system at temperatures down to 0.300 K and magnetic fields up to 12 T. PMID- 26863450 TI - Covalent Chemistry beyond Molecules. AB - Linking molecular building units by covalent bonds to make crystalline extended structures has given rise to metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), thus bringing the precision and versatility of covalent chemistry beyond discrete molecules to extended structures. The key advance in this regard has been the development of strategies to overcome the "crystallization problem", which is usually encountered when attempting to link molecular building units into covalent solids. Currently, numerous MOFs and COFs are made as crystalline materials in which the large size of the constituent units provides for open frameworks. The molecular units thus reticulated become part of a new environment where they have (a) lower degrees of freedom because they are fixed into position within the framework; (b) well-defined spatial arrangements where their properties are influenced by the intricacies of the pores; and (c) ordered patterns onto which functional groups can be covalently attached to produce chemical complexity. The notion of covalent chemistry beyond molecules is further strengthened by the fact that covalent reactions can be carried out on such frameworks, with full retention of their crystallinity and porosity. MOFs are exemplars of how this chemistry has led to porosity with designed metrics and functionality, chemically-rich sequences of information within their frameworks, and well-defined mesoscopic constructs in which nanoMOFs enclose inorganic nanocrystals and give them new levels of spatial definition, stability, and functionality. PMID- 26863451 TI - Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis. AB - Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can improve strength in individuals with MS, however; it remains unclear the duration of RST that is needed to make strength gains and how to adapt hip strengthening exercises for individuals of varying strength using only resistance bands. This paper describes the methodology to set up and implement an adapted resistance strength training program, using resistance bands, for individuals with MS. Directions for pre- and post-strength tests to evaluate efficacy of the strength training program are included. Safety features and detailed instructions outline the weekly program content and progression. Current evidence is presented showing that significant strength gains can be made within 8 weeks of starting a RST program. Evidence is also presented showing that resistance strength training can be successfully adapted for individuals with MS of varying strength with little equipment. PMID- 26863452 TI - Histology-based prediction of lymph node metastases in early gastric cancer as decision guidance for endoscopic resection. AB - BACKGROUND: Selected cases of early gastric cancer (EGC) can be successfully treated by endoscopic therapy if the risk of concurrent lymph node metastases (LNM) is negligible. Criteria for endoscopic resection based on risk factor analyses for LNM have been established mainly in Asia. However, it is not clear to what extent these recommendations can be transferred to Western collectives. The aim of this study was to analyze predictors for LNM in EGC in a Western study population. METHODS: From our institutional archive, we selected all patients with gastric adenocarcinoma who had undergone gastrectomy with lymphadenectomy (1972 - 2005). Among 1970 patients 275 cases with EGC were identified. Clinical and pathological data were collected and logistic regression analyses performed. RESULTS: LNM were present in 36/275 (13.1%) patients. With deeper invasion proportion of LNM increased. At submucosa level (sm1), patients were almost five times more likely to have LNM than at mucosa levels.Multivariable logistic regression analysis revealed lymphovascular invasion, diffuse- and mixed-type, and invasion depth as significant independent histopathological predictors of LNM. In patients with intestinal type according to Lauren and no lymphovascular invasion, we found only one LNM-positive case out of 43 patients in the pT1b (sm1 and sm2) groups. CONCLUSIONS: Our results underline the recommendation of most guidelines that endoscopic resection is sufficient for pT1a ECG because of the low incidence of LNM in this group. However, there seems also a role for endoscopic therapy in cases of pT1b (sm1/2) EGC with intestinal type differentiation and no lymphovascular invasion. PMID- 26863453 TI - Effect of postoperative radiotherapy for squamous cell cancer of the breast in a surveillance epidemiology and end results population-based study. AB - The therapeutic value of postoperative radiotherapy (RT) for squamous cell cancer of the breast (SCCB) is unclear. This retrospective study used a population-based national registry to determine the impact of postoperative RT on survival of women with SCCB. The Surveillance Epidemiology and End Results (SEER) database was used to identify females with SCCB who underwent primary surgical resection from 1973 to 2012. Kaplan-Meier survival analysis and Cox regression proportional hazard methods were used to determine the impact of RT following resection associated with cause-specific survival (CSS) and overall survival (OS). A total of 523 patients met the eligibility criteria. The median follow-up time was 55 months, the 10-year CSS and OS rates were 65.6%, and 46.0%, respectively. A total of 167 patients (31.9%) received postoperative RT. Multivariate analysis indicated that advanced pT and pN stage, and no postoperative RT were independently associated with poor OS; advanced pT and pN stage were independently associated with poor CSS. Postoperative RT was significantly associated with improved 10-year OS (54.5% vs. 42.0%, P =.001), but had no effect on CSS (P =.217). Analysis of patients with different stages of SCCB indicated that RT was associated with improved CSS (P =.047) and OS (P <.001) in those with stage II cancer and improved OS in patients with stage pN0 cancer (P <.001). Postoperative RT improved the survival of SCCB patients, especially in those with stage II and stage pN0 cancer. PMID- 26863454 TI - Metabolic vulnerabilities of MYC-induced cancer. PMID- 26863455 TI - OLA1 contributes to epithelial-mesenchymal transition in lung cancer by modulating the GSK3beta/snail/E-cadherin signaling. AB - Obg-like ATPase 1 (OLA1) belongs to the Obg family of P-loop NTPases, and may serve as a "molecular switch" regulating multiple cellular processes. Aberrant expression of OLA1 has been observed in several human malignancies. However, the role of OLA1 in cancer progression remains poorly understood. In this study, we used the Kaplan-Meier plotter search tool to show that increased expression of OLA1 mRNA was significantly associated with shorter overall survival in lung cancer patients. By immunohistochemical analysis we discovered that levels of OLA1 protein in lung cancer tissues were positively correlated with TNM stage and lymph node metastasis, but negatively correlated with the epithelial-mesenchymal transition (EMT) marker E-cadherin. Knockdown of OLA1 in a lung adenocarcinoma cell line rendered the cells more resistant to TGF-beta-induced EMT and the accompanied repression of E-cadherin. Furthermore, our results demonstrated that OLA1 is a GSK3beta-interacting protein and inhibits GSK3beta activity by mediating its Ser9 phosphorylation. During EMT, OLA1 plays an important role in suppressing the GSK3beta-mediated degradation of Snail protein, which in turn promotes downregulation of E-cadherin. These data suggest that OLA1 contributes to EMT by modulating the GSK3beta/Snail/E-cadherin signaling, and its overexpression is associated with clinical progression and poor survival in lung cancer patients. PMID- 26863457 TI - Ethnic Differences in Prevalence of Peripheral Artery Disease in Patients Undergoing Hemodialysis. AB - BACKGROUND: Hemodialysis patients experience poor outcomes associated with the presence of atherosclerosis, particularly lower-extremity peripheral artery disease (PAD). Prevalence of PAD is known to vary between ethnic groups; however, no information on ethnic-specific PAD prevalence in a hemodialysis cohort is available. METHODS: Data from the Canadian Kidney Dialysis Cohort Study was used in a secondary analysis of 1293 adults starting hemodialysis in three major Canadian centres. PAD diagnosis was determined through structured interview and supplemented by clinical record. Ethnicity was self-reported. RESULTS: Overall PAD prevalence was 19.1 % with no significant difference between ethnic groups. Ethnic differences observed in diabetes prevalence in the full hemodialysis group were not present in the subset of PAD patients. CONCLUSIONS: The prevalence of PAD in patients undergoing hemodialysis is high, however we found no apparent ethnic differences in prevalence between ethnic groups. PMID- 26863456 TI - Acute stress enhances the expression of neuroprotection- and neurogenesis associated genes in the hippocampus of a mouse restraint model. AB - Stress arises from an external demand placed on an organism that triggers physiological, cognitive and behavioural responses in order to cope with that request. It is thus an adaptive response useful for the survival of an organism. The objective of this study was to identify and characterize global changes in gene expression in the hippocampus in response to acute stress stimuli, by employing a mouse model of short-term restraint stress. In our experimental design mice were subjected to a one time exposure of restraint stress and the regulation of gene expression in the hippocampus was examined 3, 12 and 24 hours thereafter. Microarray analysis revealed that mice which had undergone acute restraint stress differed from non-stressed controls in global hippocampal transcriptional responses. An up-regulation of transcripts contributing directly or indirectly to neurogenesis and neuronal protection including, Ttr, Rab6, Gh, Prl, Ndufb9 and Ndufa6, was observed. Systems level analyses revealed a significant enrichment for neurogenesis, neuron morphogenesis- and cognitive functions-related biological process terms and pathways. This work further supports the hypothesis that acute stress mediates a positive action on the hippocampus favouring the formation and the preservation of neurons, which will be discussed in the context of current data from the literature. PMID- 26863458 TI - The Military Health Care System May Have the Potential to Prevent Health Care Disparities. AB - INTRODUCTION: The existence of health disparities in military populations has become an important topic of research. However, to our knowledge, this is the first study to examine health disparities, as related to access to care and health status, among active duty soldiers and their families. Specifically, the purpose of this analysis was to evaluate whether health disparities exist in access to care and health outcomes of patient satisfaction, physical health status, and mental health status according to race, gender, and sponsor rank in the population of active duty soldiers and their family members. METHODS: In this cross-sectional study, active duty army soldiers and family members were recruited from either one particular army health clinic where they received their health care or from an adjacent shopping center frequented by eligible participants. Data were collected using validated measures to assess concepts of access to care and health status. Statistical analysis, including one-way analysis of variance (ANOVA) was performed to investigate differences in study outcome measures across four key demographic subgroups: race, gender, sponsor rank, and component (active soldier or family member). RESULTS: A total of 200 participants completed the study questionnaires. The sample consisted of 45.5 % soldiers and 54.5 % family members, with 88.5 % reporting a sponsor rank in the category of junior or senior enlisted rank. Mean scores for access to care did not differ significantly for the groups race/ethnicity (p = 0.53), gender (p = 0.14), and sponsor rank (p = 0.10). Furthermore, no significant differences were observed whether respondents were active soldiers or their family members (p = 0.36). Similarly, there were no statistically significant subgroup (race/ethnicity, gender, sponsor rank, or component) differences in mean patient satisfaction, physical health, and mental health scores. DISCUSSION: In a health equity system of care such as the military health care system, active duty soldiers and their family members did not experience disparities in access to care or in important health outcomes of patient satisfaction, physical health status, or mental health status. PMID- 26863459 TI - Awareness of Human Papillomavirus Vaccine Among Adolescent African American Males Who Have Sex with Males: a Pilot Study. AB - African American adolescent males who have sex with males (MSMs) have a high prevalence of sexually transmitted diseases (STDs) that has been directly linked to lack of access to primary care providers and reluctance to disclose their sexuality. The human papillomavirus (HPV) is the most common STD with more than 40 different serotypes and can lead to anal/genital warts as well as oral and genital cancers. The HPV vaccine if taken prior to an adolescent becoming sexually active serves a prophylactic function. The HPV vaccine is approved by the Food and Drug Administration (FDA) for girls and boys; however, HPV vaccination rates among adolescents within different minority and underserved communities have been disappointing even though these groups are disproportionately infected with the HPV virus and certain male-specific cancers. Little is known about the uptake of the vaccine among African American MSMs and thus the aim of this study. This qualitative study is based on the health belief model and assessed participants' level of awareness of HPV, the HPV vaccine, and HPV-related illnesses among 24 African American male adolescents between 16 and 18 years old who self identify as MSMs. As part of a larger study, two focus groups were conducted for African American MSMs. Participants failed to understand their potential risk for HPV given the higher rates of STD infection experienced by MSMs. They expressed very little knowledge of the HPV vaccine and are also not aware of the complications of HPV virus infection. However, they were very eager to know more about the virus and the vaccine. This study demonstrates the need for the development of health communication intervention and more research targeting African American MSMs and also the need for policy change towards making the HPV vaccine routine for males especially adolescents at no cost. PMID- 26863460 TI - African-American Men with Low-Risk Prostate Cancer: Modern Treatment and Outcome Trends. AB - OBJECTIVE: To investigate the clinical characteristics and treatment patterns for African-American (AA) men with low-risk prostate cancer (PCa) using a national, population-based dataset. METHODS: We conducted a retrospective review of the Surveillance Epidemiology and End Results database 2004-2008. AA men aged >=40 years with low-risk PCa were identified. For comparison, white men were selected using the same selection criteria. We reviewed all recorded treatment modalities. Definitive treatment (DT) was defined as undergoing radiotherapy or prostatectomy. RESULTS: Overall, 7246 AA men and 47,154 white men met the criteria. Most of the patients had PSA level between 4.1 and 6.9 ng/mL (56.2 %) and received DT (76 %). Black men were younger (mean age: 62(+/-8) vs. 65(+/-10) years), less likely to receive DT (adjusted odds ratio (AOR), 0.71 [0.67-0.76]), and of those receiving DT, less likely to undergo prostatectomy (AOR, 0.58 [0.54 0.62]). Patients receiving DT had lower crude cancer-specific and overall mortality (0.17 vs. 0.41 % and 2.9 vs. 7.8 %, p value < 0.001, respectively, among blacks). The difference in overall mortality was largest among >= 75 years (5.6 vs. 18.2 %). Across age groups, blacks had higher all-cause mortality (AOR, 1.45 [1.13-1.87] and 1.56[1.31-1.86] for <65 and >= 65 years, respectively). CONCLUSION: Our study of a large modern cohort of men with low-risk PCa demonstrates significant lower receipt of DT, lower receipt of prostatectomy among those receiving DT, and lower survival for black men compared to their white counterparts. Older men were less likely to receive DT. Patients who received DT had better survival. The survival difference was most striking among the elderly. PMID- 26863461 TI - Racial/Ethnic Disparities in HPV Vaccine Uptake Among a Sample of College Women. AB - OBJECTIVE: The aim of this study is to determine the association between racial/ethnic status and uptake and completion of the HPV vaccine series in college women. METHODS: Participants were recruited from a large university in North Central Florida. Young women between 18 and 26 years of age who were currently enrolled in a college course comprised the study sample. Participants completed an anonymous online survey that assessed sociodemographic characteristics, sexual behaviors, gynecological healthcare utilization, and perception of risk to HPV-associated diseases. Multivariable analysis was conducted to determine the relationship between racial/ethnic status and HPV vaccination status. RESULTS: Of the 835 with complete data (51.0 % white, 16.5 % black, 13.8 % Hispanic, 8.3 % Asian, and 9.9 % other), 53 % had initiated (receipt of at least one dose) the three-dose HPV vaccine series. Of those who initiated, 70 % indicated that they had completed all three doses. In adjusted analysis, blacks were significantly less likely to report initiation [adjusted prevalence ratio (aPR) = 0.78; 95 % confidence interval (CI), 0.63, 0.97] and completion (aPR = 0.64; 95 % CI: 0.48, 0.84) of the three dose HPV vaccine as compared to whites. Although completion rates were lower in all other racial/ethnic groups as compared to whites, these rates did not reach statistical significance. CONCLUSIONS: These findings are consistent with research from other types of settings and demonstrate lower initiation and completion rates of HPV vaccine among black women attending college as compared to their white counterparts. Additional research is needed to understand why black college women have low initiation and completion rates. PMID- 26863462 TI - Racial Differences in Satisfaction with VA Health Care: A Mixed Methods Pilot Study. AB - INTRODUCTION: As satisfied patients are more adherent and play a more active role in their own care, a better understanding of factors associated with patient satisfaction is important. PURPOSE: In response to a United States Veterans Administration (VA) Hospital Report Card that revealed lower levels of satisfaction with health care for African Americans compared to Whites, we conducted a mixed methods pilot study to obtain preliminary qualitative and quantitative information about possible underlying reasons for these racial differences. METHODS: We conducted telephone interviews with 30 African American and 31 White veterans with recent inpatient and/or outpatient health care visits at three urban VA Medical Centers. We coded the qualitative interviews in terms of identified themes within defined domains. We summarized racial differences using ordinal logistic regression for Likert scale outcomes and used random effects logistic regression to assess racial differences at the domain level. RESULTS: Compared to Whites, African Americans were younger (p < 0.001) and better educated (p = 0.04). Qualitatively, African Americans reported less satisfaction with trust/confidence in their VA providers and healthcare system and less satisfaction with patient-provider communication. Quantitatively, African Americans reported less satisfaction with outpatient care (odds ratio = 0.28; 95 % confidence interval (CI) 0.10-0.82), but not inpatient care. At the domain level, African Americans were significantly less likely than Whites to express satisfaction themes in the domain of trust/confidence (odds ratio = 0.36; 95 % CI 0.18-0.73). CONCLUSION: The current pilot study demonstrates racial differences in satisfaction with outpatient care and identifies some specific sources of dissatisfaction. Future research will include a large national cohort, including Hispanic veterans, in order to gain further insight into the sources of racial and ethnic differences in satisfaction with VA care and inform future interventions. PMID- 26863463 TI - Fruit and Vegetable Perceptions Among Caregivers of American Indian Toddlers and Community Stakeholders: a Qualitative Study. AB - American Indians experience higher rates of obesity than any other ethnic group living in the USA. This disparity begins to develop in early childhood, and the excess weight carried by American Indian children contributes to health conditions that can affect their quality of life by the time they enter preschool. These children consume less than recommended amounts of fruits and vegetables, a dietary pattern that may be related to the development of obesity and other health conditions. This qualitative study explored the fruit and vegetable intake of American Indian toddlers through use of the information motivation-behavioral skills (IMB) model. Focus groups with caregivers of American Indian toddlers and interviews with stakeholders in American Indian communities were conducted to investigate perceptions of knowledge, motivational, and behavioral skills related to the fruit and vegetable intake of American Indian toddlers. Study participants communicated that peer support, food insecurities, cultural norms, self-efficacy, and skills to prepare fruits and vegetables impact their ability to provide fruits and vegetables to toddlers. Study participants expressed a desire to increase their knowledge regarding fruits and vegetables, including variety, benefits, and recommendations for consumption. Findings from this qualitative study provide essential insights into perceptions of fruits and vegetables among caregivers of American Indian toddlers and stakeholders in American Indian communities. Future research will utilize these findings to develop a culturally appropriate IMB-model-based fruit and vegetable-focused nutrition education program for American Indian families. PMID- 26863464 TI - Moderating Effects of Health Literacy on Change in Physical Activity Among Latinas in a Randomized Trial. AB - INTRODUCTION: Latinas report low rates of physical activity (PA) and are at risk for poor health outcomes. Language and literacy barriers impede access and utilization of PA-related resources. This study examined health literacy as a moderator on changes in moderate-to-vigorous physical activity (MVPA) in 196 Latinas enrolled in Seamos Saludables, a randomized-controlled trial of a 6-month culturally and linguistically adapted PA print intervention METHODS: Secondary analyses were conducted on demographics, acculturation and generation status, and health literacy (Newest Vital Sign). MVPA was determined by 7 day physical activity recall, assessed at baseline and 6 months. General linear models examined interaction effects between health literacy (HL), experimental condition (treatment vs. control), and generation status. RESULTS: Health literacy moderated change in MVPA from baseline to 6 months. The intervention effect was greater among first-generation Latinas with limited health literacy. DISCUSSION: Differences in health literacy level appear to influence MVPA outcomes. Formative research is recommended to ensure that materials are appropriate when developing print-based PA interventions, particularly among first-generation Latinas who are more likely to have limited health literacy. PMID- 26863465 TI - Teacher and Friend Social Support: Association with Body Weight in African American Adolescent Females. AB - The purpose of this study was to examine the direct and indirect ecological influences of teacher and friend social support on body weight and diet behaviors in African-American adolescent females. Using a quantitative, cross-sectional research design, a convenience sample of 182 urban African-American adolescent females (12-17 years old) completed a 39-item questionnaire. The questionnaire assessed perceived teacher social support, friend social support, nutrition self efficacy, and diet behaviors (with internal reliability values of scale items: alpha = 0.74, 0.81, 0.77, and 0.69 respectively). Anthropometric assessments were conducted to measure height and weight to compute BMI. Majority of the participants were in middle or early high school (65 %) and were overweight or obese (57.7 %). Both teacher social support and friend social support demonstrated a positive, indirect influence on child weight status through nutrition self-efficacy and diet behaviors following two different and specific paths of influence. Diet behaviors, in turn, demonstrated a positive, direct effect on child weight status. In the structural model, teacher social support had the greatest effect on diet behaviors, demonstrating a direct, positive influence on diet behaviors (B = 0.421, p < 0.05), but its direct effect on nutrition self-efficacy was not significant. Friend social support demonstrated a positive, direct effect on nutrition self-efficacy (B = 0.227, p < 0.05), but its direct effect on diet behaviors was not statistically significant. The study's findings call for actively addressing the childhood obesity epidemic in the school environment by implementing health behavior change strategies at various social and ecological environmental levels. PMID- 26863466 TI - Minority Use of a National Cancer Institute-Designated Comprehensive Cancer Center and Non-specialty Hospitals in Two Florida Regions. AB - PURPOSE: To examine cancer treatment disparities at a National Cancer Institute designated comprehensive cancer center (NCI-CCC) and non-specialty hospitals. MATERIALS AND METHODS: Florida hospital discharge datasets were used. ICD9-CM codes were used to define patients with female reproductive organ cancers (FROC), male reproductive organ cancers (MROC), and OTHER cancer diagnoses. A total of 7462 NCI-CCC patients and 21,875 non-specialty hospital patients were included in the statistical analysis. Data analysis was conducted in SAS 9.2. RESULTS: Increases in age reduced the odds of receiving treatment at the NCI-CCC. Male patients were more likely than female patients to be treated at the NCI-CCC. Age adjusted odds of African American and Hispanic out/inpatients being treated at the NCI-CCC were significantly lower than those of White out/inpatients. Only patients with workers' compensation, charity, or other insurance had higher odds of being treated at the NCI-CCC. The odds of minority patients receiving outpatient treatment at the NCI-CCC declined after 2005. The odds of receiving inpatient treatment at the NCI-CCC significantly increased after 2006. CONCLUSIONS: More targeted outreach by the NCI-CCC is required. However, we expect the creation of local Accountable Care Organizations (ACOs) to reduce the numbers of minority and older patients at the NCI-CCC. Coordinated quality care at ACOs implies a potential for retaining the patient market share held by non specialty hospitals and a potential for increased demand for ACO care by minority and older patients. PMID- 26863467 TI - Race and Ethnic Group Differences in Comorbid Major Depressive Disorder, Generalized Anxiety Disorder, and Chronic Medical Conditions. AB - This study tested whether race and ethnic group differences exist for lifetime major depressive disorder and/or general anxiety disorder with one or more chronic medical conditions. Data from the National Survey of American Life, which included 3570 African American, 1438 Caribbean Black, and 891 non-Hispanic White adults were analyzed. Outcomes included at least one and multiple chronic medical conditions, from a list of 14 medical conditions (e.g., arthritis, cancer, diabetes, kidney disease, stroke, heart disease, etc.). Logistic regressions were fitted to data to determine how the association between major depressive disorder, general anxiety disorder, and one or more chronic medical conditions vary across race and ethnicity. Lifetime major depressive disorder (but not lifetime general anxiety disorder) was associated with at least one chronic medical condition among African Americans and Caribbean Blacks, but not non Hispanic Whites. Lifetime major depressive disorder was similarly associated with multiple chronic medical conditions among African Americans, Caribbean Blacks, and non-Hispanic Whites. For Caribbean Blacks, stronger associations were found between major depressive disorder and general anxiety disorder with one or more chronic medical conditions compared to African Americans and non-Hispanic Whites. Findings suggest that race and ethnicity may shape the links between comorbid psychiatric disorders and chronic medical conditions. Mental health screening of individuals with chronic medical conditions in primary health-care settings may benefit from tailoring based on race and ethnicity. More research is needed to understand why associations between physical and mental health vary among race and ethnic groups. PMID- 26863468 TI - The Implementation of an Innovative High School Mentoring Program Designed to Enhance Diversity and Provide a Pathway for Future Careers in Healthcare Related Fields. AB - BACKGROUND: Although the population of diverse applicants applying to medical school has increased over recent years (AAMC Diversity in Medical Education: Facts and Figures 2012); efforts persist to ensure the continuance of this increasing trend. Mentoring students at an early age may be an effective method by which to accomplish diversity within the applicant pool. Having a diverse physician population is more likely able to adequately address the healthcare needs of our diverse population. PURPOSE: The purpose of this study is to initiate a pipeline program, called the Medical Student Mentorship Program (MSMP), designed to specifically target high school students from lower economic status, ethnic, or racial underrepresented populations. High school students were paired with medical students, who served as primary mentors to facilitate exposure to processes involved in preparing and training for careers in medicine and other healthcare-related fields as well as research. METHODS: Mentors were solicited from first and second year medical students at the University of Arizona College of Medicine-Phoenix (UACOM-P). Two separate cohorts of mentees were selected based on an application process from a local high school for the school years 2010-2011 and 2011-2012. Anonymous mentee and mentor surveys were used to evaluate the success of the MSMP. RESULTS: A total of 16 pairs of mentees and mentors in the 2010-2011 (Group 1) and 2011-2012 (Group 2) studies participated in MSMP. High school students reported that they were more likely to apply to medical school after participating in the program. Mentees also reported that they received a significant amount of support, helpful information, and guidance from their medical student mentors. Overall, feedback from mentees and mentors was positive and they reported that their participation was rewarding. Mentees were contacted 2 to 3 years post MSMP participation as sophomores or juniors in college, and all reported that they were on a pre-healthcare career track. CONCLUSION: The MSMP may serve as an effective pipeline program to promote future diversity in college and graduate training programs for future careers in science and medicine. PMID- 26863469 TI - Erratum to: The Association Between Obesity and Weight Loss Intention Weaker Among Blacks and Men than Whites and Women. PMID- 26863471 TI - Renal Transplantation in a Patient With Unsuspected Inferior Vena Cava Obliteration. AB - Vena cava thrombosis can represent a surgical challenge in the context of kidney transplantation. Selection of venous drainage in this setting should provide adequate venous outflow and minimize the risk of thrombosis and subsequent graft failure. We report the case of an adult female patient who presented for a deceased donor kidney transplant with incidental finding of complete inferior vena cava (IVC) and obliteration. After exploration of the retroperitoneal space up to the level of the obliterated IVC, a collateral venous branch was identified at the confluence of the right and left iliac veins. This was utilized as the site of the renal vein venous anastomosis. The patient recovered with immediate graft function. Follow-up ultrasound demonstrated patent vasculature without evidence of thrombosis or outflow obstruction. This report offers a surgical alternative to proceed in the case of an adult with unsuspected caval system obliteration. PMID- 26863470 TI - Isolation of CD 90+ Fibroblast/Myofibroblasts from Human Frozen Gastrointestinal Specimens. AB - Fibroblasts/myofibroblasts (MFs) have been gaining increasing attention for their role in pathogenesis and their contributions to both wound healing and promotion of the tumor microenvironment. While there are currently many techniques for the isolation of MFs from gastrointestinal (GI) tissues, this protocol introduces a novel element of isolation of these stromal cells from frozen tissue. Freezing GI tissue specimens not only allows the researcher to acquire samples from worldwide collaborators, biobanks, and commercial vendors, it also permits the delayed processing of fresh samples. The described protocol will consistently yield characteristic spindle-shaped cells with the MF phenotype that express the markers CD90, alpha-SMA and vimentin. As these cells are derived from patient samples, the use of primary cells also confers the benefit of closely mimicking MFs from disease states-namely cancer and inflammatory bowel diseases. This technique has been validated in gastric, small bowel, and colonic MF primary culture generation. Primary MF cultures can be used in a vast array of experiments over a number of passage and their purity assessed by both immunocytochemistry and flow cytometry analysis. PMID- 26863472 TI - Neurosarcoidosis Presenting as Aseptic Meningitis in an Immunosuppressed Renal Transplant Recipient. AB - BACKGROUND: Sarcoidosis is a presumptive autoimmune disorder characterized by the presence of noncaseating granulomas and is usually treated successfully with immunosuppression. METHODS AND RESULTS: Here, we describe the case of a 63-year old male renal transplant recipient with a remote history of pulmonary sarcoidosis on chronic immunosuppression who developed recurrent aseptic meningitis and underwent brain biopsy revealing a diagnosis of neurosarcoidosis. CONCLUSIONS: This case highlights the possibility of recurrence of sarcoidosis in the setting of maintenance immunosuppression, the need for heightened awareness of alternative sites of recurrence of autoimmune disease, and future studies to determine the underlying mechanism of recurrence in organ transplant recipients. PMID- 26863473 TI - Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers. AB - BACKGROUND: The mechanism through which oxygenated hypothermic machine perfusion (HMP) improves viability of human extended criteria donor (ECD) livers is not well known. Aim of this study was to examine the benefits of oxygenated HMP after static cold storage (SCS). METHODS: Eighteen ECD livers that were declined for transplantation underwent ex situ viability testing using normothermic (37 degrees C) machine perfusion (NMP) after traditional SCS (0 degrees C-4 degrees C) for 7 to 9 hours. In the intervention group (n = 6), livers underwent 2 hours of oxygenated HMP (at 12 degrees C) after SCS and before NMP. Twelve control livers underwent NMP without oxygenated HMP after SCS. RESULTS: During HMP, hepatic ATP content increased greater than 15-fold, and levels remained significantly higher during the first 4 hours of NMP in the HMP group, compared with controls. Cumulative bile production and biliary secretion of bilirubin and bicarbonate were significantly higher after HMP, compared with controls. In addition, the levels of lactate and glucose were less elevated after HMP compared with SCS preservation alone. In contrast, there were no differences in levels of hepatobiliary injury markers AST, ALT, LDH, and gamma-GT after 6 hours of NMP. Hepatic histology at baseline and after 6 hours of NMP revealed no differences in the amount of ischemic necrosis between both groups. CONCLUSIONS: Two hours of oxygenated HMP after traditional SCS restores hepatic ATP levels and improves hepatobiliary function but does not reduce (preexisting) hepatobiliary injury in ECD livers. PMID- 26863474 TI - Predominant Tubular Interleukin-18 Expression in Polyomavirus-Associated Nephropathy. AB - Polyomavirus-associated nephropathy (PVAN) occurs in a significant percentage of renal transplant recipients, with BK virus reactivation as the main causative agent. PVAN leads to tubular damage and may result in allograft loss. In this study, we analyzed the antiviral immune response in PVAN. Transcription of the proinflammatory cytokine interleukin-18 (IL-18) was significantly higher in PVAN biopsies compared with T cell-mediated rejection (TCMR) (1.42 +/- 0.20 and 0.69 +/- 0.10, respectively; *P = 0.0021). Tubular expression of IL-18 was significantly increased in PVAN compared with TCMR (2.00 +/- 0.24 and 1.333 +/- 0.13, respectively; *P = 0.028). In contrast, in TCMR, IL-18 was expressed predominantly by CD163-positive macrophages. These data suggest that the antiviral immune response in PVAN is partly coordinated by the tubular epithelium, whereas in TCMR, this may be controlled by inflammatory cells. PMID- 26863475 TI - Early Readmission After Kidney Transplantation: Examination of Discharge-Level Factors. AB - BACKGROUND: Early rehospitalization after kidney transplantation (KTx) is common and is considered a quality metric. Recipient and donor risk factors for early readmission after KTx are well studied. Little data exist on discharge-level factors associated with readmission. METHODS: We performed a single-center, retrospective cohort study between 2011 and 2015 of adult KTx recipients to examine readmission indication, risk factors, and opportunities for reduction. RESULTS: Of 462 KTxs, 145 (31.4%) were readmitted within 30 days of discharge. The primary reason for readmission was surgery-site specific in 30 cases (20.7%). Of 115 recipients with nonsurgical indications for readmission 25 (21.7%) were related to infection, 24 (20.9%) graft dysfunction, 25 (21.7%) gastrointestinal, 25 (21.7%) metabolic, and 16 (13.9%) other reasons. On multivariate analysis significant independent predictors of early readmission were electrolyte abnormalities on the day of discharge (odds ratio [OR], 1.77; 95% confidence interval [95% CI], 1.17-2.69), 3 or more comorbidities (OR, 2.01; 95% CI, 1.04 3.86), delayed graft function at the time of discharge (OR, 1.65; 95% CI, 1.00 2.70), and post-KTx hospitalization complication (OR, 1.70; 95% CI, 1.10-2.61). Among 11.7% of patients, readmission may have been attenuated by addressing the medical issue before discharge from index hospitalization. In 28.3% of patients, readmission rates may have been reduced with continued management as an outpatient or provision of observational or same-day diagnostic resources. CONCLUSIONS: Specific discharge level factors correlate with readmission irrespective of comorbidities and transplant complications. These findings may have important implications on discharge practice by aiding to identify which KTx recipients could be targeted for enhanced care transitions. Overall, potential opportunities for readmission reduction exist on multiple process levels. PMID- 26863476 TI - Kidney Transplant Readmissions: It Takes a Village to Keep This Patient Out of the Hospital! PMID- 26863477 TI - A Cell Type Independent Binary Grading System Does Not Significantly Improve Endometrial Biopsy Interpretation. AB - The revised International Federation of Gynecology and Obstetrics (FIGO) grading system is widely accepted as the standard in evaluating endometrial carcinoma on biopsy. Determination of tumor cell type [using the World Health Organization (WHO) diagnostic criteria] and grade (using FIGO) guides surgical approach. Several studies have highlighted discrepancies between biopsy and hysterectomy diagnosis. Recently, a binary grading system was proposed, yielding a low-risk and high-risk assessment but in a cell type independent (CTI) way. No study has assessed its utility in biopsy grading, a situation where this system may be particularly useful. Archived endometrial biopsies from 70 cases of endometrial carcinoma were graded by 3 independent observers using the WHO/FIGO and the CTI grading systems. The overall accuracy, interobserver agreement, and ease of use were assessed. This study found comparable substantial accuracy between the WHO/FIGO and CTI grading systems (kappa=0.71 vs. kappa=0.69), with the same setbacks in overgrading of 20.9% versus 25.6% of low-risk tumors. The CTI grading system was not superior to the WHO/FIGO grading system in accuracy of subtyping and grading and interobserver reproducibility. Although determination of cell type is difficult, it does not appear that the proposed CTI system confers any significant advantages over existing grading. PMID- 26863478 TI - Multifocal FIGO Stage IA1 Squamous Carcinoma of the Cervix: Criteria for Identification, Staging, and its Good Clinical Outcome. AB - Multifocal squamous cervical carcinomas account for up to 25% of IA1 tumors identified on excisional biopsy, yet there are no uniformly accepted histopathologic criteria for defining and staging these lesions. Here, we use a strict case definition and meticulous specimen processing from colposcopist to pathologist to identify and follow-up 25 cases of multifocal IA1 cervical squamous carcinomas identified in excisional biopsies. We stage these tumors using the dimensions of the largest focus and a minimum of 2 mm between each foci to define multifocality. The cases are followed up for a median of 7 yr with no episodes of tumor recurrence or metastasis. We also show that the prevalence of residual preinvasive (20%) and invasive disease (5%) on repeat excision/surgery are comparable to data available for unifocal IA1 cases. Our study supports the hypothesis that multifocal lesions should be staged according to largest individual focus of invasion and we emphasize the importance of meticulous specimen handling to appropriately identify multifocal tumors. In addition, our analysis suggests that outcomes are comparable to unifocal lesions and supports the hypothesis that they may be managed in a similar manner. PMID- 26863479 TI - Inter- and intratester reliability values of ultrasound imaging measurements of diaphragm movement in the thoracic and thoracolumbar curves in adolescent idiopathic scoliosis. AB - PURPOSE: The purpose of this study was to determine intertester and intratester reliability of ultrasound measurements of bilateral diaphragm excursions in the thoracic and thoracolumbar spinal curves of 31 females with adolescent idiopathic scoliosis (AIS) (mean age = 14.1 +/- 1.8 years). METHOD: Subjects were tested during tidal breathing using real-time ultrasound imaging with a 3.5 MHz curvilinear transducer. RESULTS: There were no significant differences in intratester and intertester reliability values in bilateral diaphragmatic excursions measured at the thoracolumbar spinal curve, whereas significant differences were observed in measurements taken at the thoracic spinal curve (p < 0.05). Overall, the intertester and intratester reliabilities of the thoracic and thoracolumbar curves in AIS ranged from 0.764 to 0.998. CONCLUSIONS: These findings suggest that ultrasound imaging is highly reliable between and within testers and is useful to precisely discriminate pathological diaphragm movement in idiopathic thoracic scoliosis and idiopathic thoracolumbar scoliosis. PMID- 26863480 TI - Current trends in endotoxin detection and analysis of endotoxin-protein interactions. AB - Endotoxin is a type of pyrogen that can be found in Gram-negative bacteria. Endotoxin can form a stable interaction with other biomolecules thus making its removal difficult especially during the production of biopharmaceutical drugs. The prevention of endotoxins from contaminating biopharmaceutical products is paramount as endotoxin contamination, even in small quantities, can result in fever, inflammation, sepsis, tissue damage and even lead to death. Highly sensitive and accurate detection of endotoxins are keys in the development of biopharmaceutical products derived from Gram-negative bacteria. It will facilitate the study of the intermolecular interaction of an endotoxin with other biomolecules, hence the selection of appropriate endotoxin removal strategies. Currently, most researchers rely on the conventional LAL-based endotoxin detection method. However, new methods have been and are being developed to overcome the problems associated with the LAL-based method. This review paper highlights the current research trends in endotoxin detection from conventional methods to newly developed biosensors. Additionally, it also provides an overview of the use of electron microscopy, dynamic light scattering (DLS), fluorescence resonance energy transfer (FRET) and docking programs in the endotoxin-protein analysis. PMID- 26863482 TI - Normative values for a video-force plate assessment of postural control in athletic children. AB - The objective of this study was to provide normative data for young athletes during the three stances of the modified Balance Error Scoring System (mBESS) using an objective video-force plate system. Postural control was measured in 398 athletes between 8 and 18 years of age during the three stances of the mBESS using a video-force plate rating system. Girls exhibited better postural control than boys during each stance of the mBESS. Age was not significantly associated with postural control. We provide normative data for a video-force plate assessment of postural stability in pediatric athletes during the three stances of the mBESS. PMID- 26863481 TI - Acute Kidney Injury in Neonates in the PICU. AB - OBJECTIVES: Acute kidney injury is an independent risk factor for morbidity and mortality in critically ill children in the PICU. Neonates are a particularly vulnerable subgroup regarding acute kidney injury. The objectives were to define the prevalence of acute kidney injury to assess independent risk factors, for the development of acute kidney injury, and to determine the impact of acute kidney injury on outcomes in critically ill neonates without history of cardiac surgery. DESIGN: A retrospective study of neonates (<= 28 d old and >= 32 wk of gestational age) admitted to a tertiary PICU was conducted. Acute kidney injury was classified using the Kidney Disease: Improving Global Outcomes definition. SETTING: PICU in a tertiary children's hospital. PATIENTS: A total of 80 neonates (62% male neonates) with a median gestational age of 38 weeks (interquartile range, 37-39 wk) were reviewed. INTERVENTION: None. MEASUREMENT AND MAIN RESULTS: Acute kidney injury was found in 35% (n = 28) of neonates. Fourteen (50%) reached stage I, 8 (29%) stage II, and 6 (21%) stage III acute kidney injury. Younger age was associated with acute kidney injury (p = 0.016; odds ratio, 0.93; CI, 0.88 0.98). In regression analysis adjusted for age and gender, bacteremia (p = 0.014; odds ratio, 5.4; CI, 1.4-20.4) and maximum sodium concentration (p = 0.02; odds ratio, 1.12; CI, 1.02-1.24) were associated with acute kidney injury. Mortality (p = 0.03) and length of mechanical ventilation (p = 0.001) were significantly higher in neonates with acute kidney injury compared with those without acute kidney injury. In an adjusted regression model, stages 2 and 3 combined were associated with increased mortality (p = 0.02; odds ratio, 5.64; CI, 1.33-23.8), length of ventilation (p = 0.016; beta, 12.2; CI, 2.39-22.0), and length of stay (p = 0.049; beta, 12.2; CI, 0.073-24.3). CONCLUSIONS: Acute kidney injury is common in neonates not requiring cardiac surgery and is associated with increased morbidity and mortality. Age, bacteremia, and maximum sodium concentration are independently associated with the development of acute kidney injury in this population. PMID- 26863483 TI - Single-leg postural stability deficits following anterior cruciate ligament reconstruction in pediatric and adolescent athletes. AB - The objective of this study was to compare the postural stability of pediatric and adolescent athletes without anterior cruciate ligament injury with those who underwent anterior cruciate reconstruction (ACLR). Postural stability ratings derived from a video-force plate system during the three stances of the modified Balance Error Scoring System were collected from pediatric and adolescent athletes who underwent ACLR (N=24; mean 1.2 years after surgery) and from uninjured controls (N=479). The postural control rating was calculated as the mean of the displacement and variance of the torso and center of pressure data, normalized on a scale from 0 to 100. A higher rating indicates greater postural stability. Participants who underwent ACLR showed lower postural stability ratings during single-leg stance compared with uninjured controls (40.0 vs. 48.7; P=0.037). ACLR is associated with deficits in postural stability. PMID- 26863484 TI - The Sweetest Thing: Regulation of Macronutrient Preference by FGF21. AB - Links between FGF21 and carbohydrate consumption have recently been described, with both genomic associations and elevated FGF21 levels in healthy subjects following sugar ingestion. In this issue, von Holstein-Rathlou et al. (2016) and Talukdar et al. (2016) demonstrate a mechanistic role for FGF21 in the regulation of macronutrient preference. PMID- 26863485 TI - Mitochondrial Damage Induces Senescence with a Twisted Arm. AB - Cellular senescence is a damage response characterized by a stable cell-cycle arrest and an intense secretion of cytokines. In this issue of Cell Metabolism, Wiley et al. (2016) report that, in the case of mitochondrial damage, senescence occurs with an atypical secretory phenotype, in both adipose tissue and skin. PMID- 26863486 TI - Regulatory T Cell Immunotherapy for Type 1 Diabetes: A Step Closer to Success? AB - Regulatory T cell (Treg) therapy has shown promises in experimental models of type 1 diabetes (T1D) and other autoimmune diseases. Now, Bluestone et al. (2015) report in a phase 1, dose-escalation study that ex vivo-expanded autologous polyclonal Treg therapy is safe and well tolerated in adult patients with recent onset T1D. PMID- 26863487 TI - HIF-1alpha Promotes Glutamine-Mediated Redox Homeostasis and Glycogen-Dependent Bioenergetics to Support Postimplantation Bone Cell Survival. AB - Cell-based therapy is a promising strategy in regenerative medicine, but the poor survival rate of the implanted cells remains a major challenge and limits clinical translation. We preconditioned periosteal cells to the hypoxic and ischemic environment of the bone defect site by deleting prolyl hydroxylase domain-containing protein 2 (PHD2), resulting in hypoxia-inducible factor 1 alpha (HIF-1alpha) stabilization. This strategy increased postimplantation cell survival and improved bone regeneration. The enhanced cell viability was angiogenesis independent but relied on combined changes in glutamine and glycogen metabolism. HIF-1alpha stabilization stimulated glutaminase-mediated glutathione synthesis, maintaining redox homeostasis at baseline and during oxidative or nutrient stress. Simultaneously, HIF-1alpha signaling increased glycogen storage, preventing an energy deficit during nutrient or oxygen deprivation. Pharmacological inhibition of PHD2 recapitulated the adaptations in glutamine and glycogen metabolism and, consequently, the beneficial effects on cell survival. Thus, targeting cellular metabolism is an appealing strategy for bone regeneration and cell-based therapy in general. PMID- 26863488 TI - SnapShot: Stress and Disease. AB - Perturbation of an organism's homeostasis by stress can trigger biological or behavioral adaptation and accelerate onset and course of several diseases. Signaling triggered by norepinephrine or epinephrine (via adrenergic receptors) and cortisol (through glucocorticoid receptors) has profound effects on dampening immune responses, accelerating cancer progression and increasing the risk of cardiovascular, metabolic, and colonic diseases. To view this SnapShot, open or download the PDF. PMID- 26863489 TI - Generating a "Humanized" Drosophila S2 Cell Line Sensitive to Pharmacological Inhibition of Kinesin-5. AB - Kinetochores are large protein-based structures that assemble on centromeres during cell division and link chromosomes to spindle microtubules. Proper distribution of the genetic material requires that sister kinetochores on every chromosome become bioriented by attaching to microtubules from opposite spindle poles before progressing into anaphase. However, erroneous, non-bioriented attachment states are common and cellular pathways exist to both detect and correct such attachments during cell division. The process by which improper kinetochore-microtubule interactions are destabilized is referred to as error correction. To study error correction in living cells, incorrect attachments are purposely generated via chemical inhibition of kinesin-5 motor, which leads to monopolar spindle assembly, and the transition from mal-orientation to biorientation is observed following drug washout. The large number of chromosomes in many model tissue culture cell types poses a challenge in observing individual error correction events. Drosophila S2 cells are better subjects for such studies as they possess as few as 4 pairs of chromosomes. However, small molecule kinesin 5 inhibitors are ineffective against Drosophila kinesin-5 (Klp61F). Here we describe how to build a Drosophila cell line that effectively replaces Klp61F with human kinesin-5, which renders the cells sensitive to pharmacological inhibition of the motor and suitable for use in the cell-based error correction assay. PMID- 26863490 TI - Bioluminescence Imaging of an Immunocompetent Animal Model for Glioblastoma. AB - In contrast to commonly reported human glioma xenograft animal models, GL261 murine glioma xenografts recapitulate nearly all relevant clinical and histopathologic features of the human disease. When GL261 cells are implanted intracranially in syngeneic C57BL/6 mice, the model has the added advantage of maintaining an intact immune microenvironment. Stable expression of luciferase in GL261 cells allows non-invasive cost effective bioluminescence monitoring of intracranial tumor growth. We have recently demonstrated that luciferase expression in GL261 cells does not affect the tumor growth properties, tumor cell immunomodulatory cytokine expression, infiltration of immune cells into the tumor, or overall survival of animals bearing the intracranial tumor. Therefore, it appears that the GL261 luciferase glioma model can be useful in the study of novel chemotherapeutic and immunotherapeutic modalities. Here we report the technique for generating stable luciferase expression in GL261 cells and how to study the in vitro and in vivo growth of the tumor cells by bioluminescence imaging. PMID- 26863491 TI - Concurrent agostic and tetrel bonding interactions in lead(ii) complexes with an isonicotinohydrazide based ligand and several anions. AB - In this manuscript we report for the first time the concurrent agostic and tetrel bonding interactions involving the heaviest tetrel atom (Pb) in N' (phenyl(pyridin-2-yl)methylene)isonicotinohydrazide-PbX complexes (X = Cl, I, NCS, NO2). PMID- 26863492 TI - Detection of nitroaromatics in the solid, solution, and vapor phases using silicon quantum dot sensors. AB - Silicon quantum dots (Si-QDs) represent a well-known QD fluorophore that can emit throughout the visible spectrum depending on the interface structure and surface functional group. Detection of nitroaromatic compounds by monitoring the luminescence response of the sensor material (typically fluorescent polymers) currently forms the basis of new explosives sensing technologies. Freestanding silicon QDs may represent a benign alternative with a high degree of chemical and physical versatility. Here, we investigate dodecyl and amine-terminated Si-QD luminescence response to the presence of nitrobenzene and dinitrotoluene (DNT) in various solid, solution, and vapor forms. For dinitrotoluene vapor the 3sigma detection limit was 6 ppb for monomer-terminated QDs. For nitroaromatics dissolved in toluene the detection limit was on the order of 400 nM, corresponding to ~100 pg of material distributed over ~1 cm(2) on the sensor surface. Solid traces of nitroaromatics were also easily detectable via a simple 'touch test'. The samples showed minimal interference effects from common contaminants such as water, ethanol, and acetonitrile. The sensor can be as simple and inexpensive as a small circle of filter paper dipped into a QD solution, with a single vial of QDs able to make hundreds of these sensors. Additionally, a trial fiber-optic sensor device was tested by applying the QDs to one end of a 2 * 2 fiber coupler and exposing them to controlled DNT vapor. Finally, the quenching mechanism was explored via luminescence dynamics measurements and is different for blue (amine) and red (dodecyl) fluorescent silicon QDs. PMID- 26863493 TI - Well-aligned Nd-doped SnO2 nanorod layered arrays: preparation, characterization and enhanced alcohol-gas sensing performance. AB - Well-oriented neodymium doped SnO2 layered nanorod arrays were synthesized by a substrate-free hydrothermal route using sodium stannate and sodium hydroxide at 210 degrees C. The morphology and phase structure of the Nd-doped SnO2 nanoarrays were investigated by X-ray powder diffraction spectroscopy, scanning electron microscopy, transmission electron microscopy, Raman scattering spectroscopy, X-ray photoelectron spectroscopy and the BET method. The results demonstrated that the Nd-doped SnO2 layered nanorod arrays showed a unique nanostructure combined together with double layered arrays of nanorods with a diameter of 12 nm and a length of several hundred nanometers. The Nd-doped layered SnO2 nanoarrays kept the crystal structure of the bulk SnO2 and possessed more surface defects caused by the Nd ions doped into the SnO2 lattice. The Nd dopant acts as a crystallite growth inhibitor to prevent the growth of SnO2 nanorods. An investigation into the gas-sensing properties indicated that the optimized doping level of 3.0 at% Nd-doped SnO2 layered nanorod arrays exhibited an excellent sensing response toward alcohol at a lower temperature of 260 degrees C. The enhanced sensor performance was attributed to the higher specific surface area, multi-defect surface structure and the excellent catalytic properties of Nd dopant that is able to increase the amount of active sites on the surface of semiconducting oxides. The Nd-doped SnO2 nanoarray sensors were considered to be a promising candidate for trace alcohol detections in environmental gas monitoring. PMID- 26863494 TI - Synthesis of a rhodium(i) germyl complex: a useful tool for C-H and C-F bond activation reactions. AB - The dihydrido germyl complex cis,fac-[Rh(GePh3)(H)2(PEt3)3] (2) was synthesized by an oxidative addition of HGePh3 at [Rh(H)(PEt3)3] (1). Treatment of 2 with neohexene generated the rhodium(i) germyl complex [Rh(GePh3)(PEt3)3] (3). Alternatively, treatment of the methyl complex [Rh(CH3)(PEt3)3] (4) with HGePh3 furnished at room temperature also 3. Low-temperature NMR measurements revealed an initial formation of the oxidative addition product fac [Rh(GePh3)(H)(CH3)(PEt3)3] (5), which transforms into the intermediate complex [Rh(GePh3)(H)(CH3)(PEt3)2] (6) by dissociation of a triethylphosphine ligand. The reductive elimination of methane and coordination of PEt3 afforded the germyl complex 3. Treatment of 3 with CO gave the biscarbonyl complex [Rh(GePh3)(CO)2(PEt3)2] (7). The molecular structures of the complexes 2, 3 and 7 were determined by X-ray crystallography. The germyl complex 3 reacted with 2,3,5,6-tetrafluoropyridine or pentafluorobenzene to furnish the C-H activation products [Rh(4-C5NF4)(PEt3)3] (8) and [Rh(C6F5)(PEt3)3] (9), respectively. The reaction of 3 with hexafluorobenzene or perfluorotoluene gave selectively the C-F activation products 9 and [Rh(4-C6F4CF3)(PEt3)3] (10). Treatment of 3 with pentafluoropyridine resulted in the formation of the C-F activation products 8 and [Rh(2-C5NF4)(PEt3)3] (11) in a 1 : 10 ratio. The two isomeric activation compounds [Rh{(E)-CF[double bond, length as m-dash]CF(CF3)}(PEt3)3] (12) and [Rh{(Z)-CF[double bond, length as m-dash]CF(CF3)}(PEt3)3] (13) were obtained in a 3 : 1 ratio by reaction of 3 with hexafluoropropene. On exposure to oxygen the highly air sensitive complex 12 reacts to yield the peroxido-bridged dirhodium complex [Rh{(E)-CF[double bond, length as m-dash]CF(CF3)}(MU-kappa(1):eta(2) O2)(PEt3)2]2 (14). The molecular structure of 14 was determined by X-ray crystallography. PMID- 26863495 TI - Descemet Membrane Detachment in Femtosecond Laser-Assisted Cataract Surgery. AB - PURPOSE: To report a case series of 4 patients with Descemet membrane detachment (DMD) after undergoing femtosecond laser-assisted cataract surgery incisions. METHODS: Case report. RESULTS: DMD was noted at the secondary incision (n = 2) or at the main incision (n = 2). All the secondary incision and 1 main incision DMD were resolved with intraoperative maneuvers. Delay in recognizing DMD intraoperatively at the principal incision in 1 case led to inadvertent aspiration of a part of it and persistent postoperative corneal edema. This complication was handled with Descemet membrane endothelial keratoplasty 1 month after initial surgery. CONCLUSIONS: DMD can occur after femtosecond laser assisted cataract surgery, although it is a rare complication as it is in traditional phacoemulsification. The surgeon must be prepared to recognize it, manage it intraoperatively, and treat it postoperatively to reduce the risk of permanent damage to the eye. PMID- 26863496 TI - Corneal Patch Graft: A New Approach for Scleral Necrosis Secondary to Plaque Radiotherapy. AB - PURPOSE: To evaluate the anatomical outcomes of corneal patch grafts in patients with progressive scleral necrosis secondary to plaque radiotherapy used for uveal malignant melanoma management. METHODS: In this case series, 4 patients with progressive scleral necrosis after Ru-106 plaque radiotherapy underwent corneal patch grafts with the anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue to strengthen the sclera and to improve appearance of the eye. RESULTS: Ciliary body involvement was evident in all cases. All 4 patients had received radiation doses of 400 Gy or more to the tumor base. The mean time interval between plaque radiotherapy and scleral necrosis was 24.5 +/- 7.5 months (range, 18-34 months). Successful results were achieved in all patients with tectonic graft. No patients experienced graft thinning, rejection, infection, or tumor recurrence in a mean follow-up of 28.5 +/- 7.9 months (range, 20-39 months). CONCLUSIONS: Corneal patch graft by anterior corneal button from Descemet stripping automated endothelial keratoplasty donor tissue results in successful restoration of globe integrity and satisfactory cosmetic appearance in patients with scleral necrosis secondary to plaque radiotherapy. PMID- 26863497 TI - Successful Treatment of Acute Ocular-Involving Toxic Epidermal Necrolysis Using Amniotic Membrane Suture Fixated to Custom Designed Symblepharon Rings. AB - PURPOSE: The purpose of this study is to describe a novel technique using amniotic membrane suture-fixated onto custom-designed symblepharon rings in a patient with acute toxic epidermal necrolysis (TEN). METHODS: A 61-year-old man developed bilateral symblephara and severe ocular surface inflammation from Stevens-Johnson syndrome/TEN secondary to allopurinol. Eight days after admission, he was treated with placement of custom-designed symblepharon rings, designed by one of the authors (A.A.), covered with amniotic membrane. This method was used to allow for efficient placement of the membrane and to minimize operative time and perioperative risks due to his worsening systemic condition. RESULTS: On postoperative day 49, his visual acuity was 20/20 in the right eye and 20/25 in the left eye. Both eyes were quiet with only small symblephara noted temporally. CONCLUSIONS: The use of amniotic membrane suture-fixated to custom designed symblepharon rings provides sufficient coverage of the ocular surface, leading to excellent visual and clinical outcomes by reducing inflammation and protecting the ocular surface from the cicatrizing sequelae associated with ocular-involving TEN. This novel technique is less invasive, more time efficient, and likely safe for even the most critically ill patients with significant risk for mortality, thus allowing any treating ophthalmologist to comfortably perform this important sight-saving procedure. PMID- 26863498 TI - An Adult Case of Fulminant Mumps Keratitis With Positive Viral RNA in Aqueous Humor Detected by RT-PCR. AB - PURPOSE: To report an adult case of mumps keratitis with mumps virus in aqueous humor and decreased corneal endothelial cell density. METHODS: Case report. RESULTS: A 60-year-old female with a 39 degrees C fever and bilateral parotid swelling diagnosed with mumps and treated for photophobia, pain, redness, and decreased vision in 1 eye, was referred to our hospital when her condition deteriorated despite receiving betamethasone phosphate instillation and antiglaucoma agents for elevated intraocular pressure (52 mm Hg) and iritis. Her right eye was normal, whereas her left eye showed 20/400 visual acuity, 21 mm Hg intraocular pressure, ciliary injection and edema, opacity, and Descemet folds in the entire cornea. Round white keratic precipitates were present on the posterior corneal surface, whereas anterior chamber cells could not be examined in detail because of corneal edema. Mumps virus was detected by reverse transcriptase polymerase chain reaction in an aqueous humor sample taken at the time of admission. Following diagnosis of keratitis, administration of 30 mg oral prednisolone daily and frequent instillation of betamethasone phosphate steadily improved her corneal edema and opacity. In her left eye, visual acuity recovered to 20/16 and keratitis was resolved at 4 weeks; however, corneal endothelial cell density was significantly decreased to less than 400 per square millimeter. CONCLUSIONS: Mumps keratitis may cause severe corneal endothelial cell loss. PMID- 26863499 TI - Polarimetric Interferometry for Assessment of Corneal Stromal Lamellae Orientation. AB - PURPOSE: To analyze corneal stromal lamellae orientation in normal subjects and patients with various corneal conditions using a polarimetric interferometer. METHODS: Thirty-two healthy control subjects (59 eyes) and 16 patients (22 eyes) with corneal conditions or postkeratoplasty were included in the study. All patients were imaged using the interferometer and slit lamp photography. The interferometer produces an orthogonal cross-like image of stromal lamellae by illuminating the cornea in phase-light polarization angle. Corneal haze was graded on a scale from 0 to 4. Interferometer cross-like images were graded on a scale from 0 to 5 by a masked observer. Keratometry, corneal central pachymetry, and optical densitometry were obtained with Scheimpflug corneal tomography. RESULTS: The cross-like image was observed in 31 of 32 healthy control subjects (58 of 59 eyes) and in 13 of 16 patients (19 of 22 eyes). The image was not detectable in 3 patients, 1 with total corneal neovascularization and scarring, 1 with central leukoma, and 1 with failed deep lamellar keratoplasty. Corneal haze was the main factor obscuring the cross-like image (P < 0.05). Clarity of the images was influenced by older age, steeper keratometry, higher pachymetry, and optical density (P < 0.05). There was no correlation between the orientation of the keratometric axes and the orientation of the 2 arms of the cross-like image (P > 0.05). CONCLUSIONS: Corneal stromal lamellae orientation can be efficiently assessed and displayed as a cross-like image by the polarimetric interferometer. Stromal lamellae orientation imaging may have potential implications in corneal diagnostics and surgery. PMID- 26863500 TI - Fungal Keratitis Caused by Exserohilum, An Emerging Pathogen. AB - PURPOSE: To determine the epidemiology, risk factors, clinical features, and prognosis of fungal keratitis caused by Exserohilum. METHODS: All culture-proven cases of keratomycosis caused by Exserohilum presented from January 2012 to December 2014 were retrospectively analyzed using a computerized database. RESULTS: Among 1542 cases of keratomycosis, 47 (3%) were due to Exserohilum. The mean age of presentation was 50.4 years. Males (n = 32; 68%) were more commonly affected than females (n = 15; 32%). A history of trauma was present in most of the cases (n = 38; 80.9%). The mean time of the first visit to the hospital was 6.2 days after onset of symptoms. Most of the patients (n = 24; 72.3%) had central or paracentral ulcers. The infiltrate was confined to the superficial one third of the stroma in 39 patients (83%). Most of the patients (89.4%) responded well to topical treatment (natamycin 5% for ulcers <5 mm; voriconazole 1% was added for ulcers >5 mm or with hypopyon); 4 patients (8.5%) required therapeutic penetrating keratoplasty and 1 patient (2.1%) progressed to endophthalmitis, requiring evisceration. The mean best-corrected visual acuity in the medically treated patients improved from 0.89 (logMAR) at presentation to 0.77 at the completion of treatment (P = 0.015). CONCLUSIONS: This study signifies the importance of this new emerging pathogen that was generally regarded as rare in the past. The infection seems to be more prevalent than previously thought, especially in hot and humid areas. Vision is likely to improve if the infection is diagnosed and appropriate topical treatment is started early. PMID- 26863501 TI - Epithelial Ingrowth Following Endothelial Keratoplasty. AB - PURPOSE: To present a large case series of epithelial ingrowth or implantation following endothelial keratoplasty (EK) with the purpose of identifying the common causes as well as the various clinical presentations. We aim to determine the typical clinical course and the most effective treatment for this rare but serious complication. METHODS: This is a retrospective study of 13 patients who developed epithelial ingrowth or implantation post-EK. Slit lamp photographs were independently examined along with other diagnostic imaging and histopathology to confirm the diagnosis. Patient medical records including operative reports were reviewed to determine the number of surgeries that occurred before EK and details of surgical technique, for example, whether venting incisions were performed. Records from follow-up visits were reviewed to determine the natural progression and management of these cases. The literature was reviewed and a meta-analysis was performed. RESULTS: The patients were divided into 5 groups according to the type of epithelial presentation. Eight patients had involvement within the interface away from the visual axis. One patient had ingrowth in the interface within the visual axis, 2 had retrocorneal involvement, and 1 had anterior chamber involvement. One had both retrocorneal and anterior chamber involvement. Venting incisions were performed in 8 patients, but only 1 had ingrowth related to the venting incision. Nine patients were observed without evidence of significant progression. Four patients had surgical treatment to remove the epithelium. CONCLUSIONS: Epithelial ingrowth or implantation occurs most commonly within the interface away from the visual axis and typically does not progress. The presentation of a homogeneous gray-white interface opacity is characteristic. Ingrowth can result from venting incisions, but rarely does. Other causes are eccentric trephination or loose donor or host epithelium being dragged into the eye at the time of surgery. PMID- 26863502 TI - Continuous Adductor Canal Blocks: Does Varying Local Anesthetic Delivery Method (Automatic Repeated Bolus Doses Versus Continuous Basal Infusion) Influence Cutaneous Analgesia and Quadriceps Femoris Strength? A Randomized, Double-Masked, Controlled, Split-Body Volunteer Study. AB - BACKGROUND: It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for adductor canal perineural catheters. Therefore, we tested the hypothesis that scheduled bolus administration is superior or noninferior to a continuous infusion on cutaneous knee sensation in volunteers. METHODS: Bilateral adductor canal catheters were inserted in 24 volunteers followed by ropivacaine 0.2% administration for 8 hours. One limb of each subject was assigned randomly to a continuous infusion (8 mL/h) or automated hourly boluses (8 mL/bolus), with the alternate treatment in the contralateral limb. The primary end point was the tolerance to electrical current applied through cutaneous electrodes in the distribution of the anterior branch of the medial femoral cutaneous nerve after 8 hours (noninferiority delta: -10 mA). Secondary end points included tolerance of electrical current and quadriceps femoris maximum voluntary isometric contraction strength at baseline, hourly for 14 hours, and again after 22 hours. RESULTS: The 2 administration techniques provided equivalent cutaneous analgesia at 8 hours because noninferiority was found in both directions, with estimated difference on tolerance to cutaneous current of -0.6 mA (95% confidence interval, -5.4 to 4.3). Equivalence also was found on all but 2 secondary time points. CONCLUSIONS: No evidence was found to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using an adductor canal perineural catheter at 8 mL/h decreases cutaneous sensation in the distribution of the anterior branch of the medial femoral cutaneous nerve. PMID- 26863503 TI - Non-aqueous Electrode Processing and Construction of Lithium-ion Coin Cells. AB - Research into new and improved materials to be utilized in lithium-ion batteries (LIB) necessitates an experimental counterpart to any computational analysis. Testing of lithium-ion batteries in an academic setting has taken on several forms, but at the most basic level lies the coin cell construction. In traditional LIB electrode preparation, a multi-phase slurry composed of active material, binder, and conductive additive is cast out onto a substrate. An electrode disc can then be punched from the dried sheet and used in the construction of a coin cell for electrochemical evaluation. Utilization of the potential of the active material in a battery is critically dependent on the microstructure of the electrode, as an appropriate distribution of the primary components are crucial to ensuring optimal electrical conductivity, porosity, and tortuosity, such that electrochemical and transport interaction is optimized. Processing steps ranging from the combination of dry powder, wet mixing, and drying can all critically affect multi-phase interactions that influence the microstructure formation. Electrochemical probing necessitates the construction of electrodes and coin cells with the utmost care and precision. This paper aims at providing a step-by-step guide of non-aqueous electrode processing and coin cell construction for lithium-ion batteries within an academic setting and with emphasis on deciphering the influence of drying and calendaring. PMID- 26863504 TI - Targeting the glial-derived neurotrophic factor and related molecules for controlling normal and pathologic pain. AB - INTRODUCTION: Glial-derived neurotrophic factor (GDNF) and its family of ligands (GFLs) have several functions in the nervous system. As a survival factor for dopaminergic neurons, GDNF was used in clinical trials for Parkinson's disease. GFLs and their receptors are also potential targets for new pain-controlling drugs. Although molecules with analgesic activities in rodents mostly failed to be effective in translational studies, this potential should not be underestimated. AREAS COVERED: The circuitry, molecular, and cellular mechanisms by which GFLs control nociception and their intervention in inflammatory and neuropathic pain are considered first. The problems related to effective GDNF delivery to the brain and the possibility to target the GFL receptor complex rather than its ligands are then discussed, also considering the use of non peptidyl agonists. EXPERT OPINION: In nociceptive pathways, an ideal drug should either: i) target the release of endogenous GFLs from large dense-cored vesicles (LGVs) by acting, for example, onto the phosphatidylinositol-3-phosphate [PtdIns(3)P] pool, which is sensitive to Ca(2+) modulation, or ii) target the GFL receptor complex. Besides XIB403, a tiol molecule that enhances GFRalpha family receptor signaling, existing drugs such as retinoic acid and amitriptyline should be considered for effective targeting of GDNF, at least in neuropathic pain. The approach of pain modeling in experimental animals is discussed. PMID- 26863505 TI - Highly Ordered Periodic Au/TiO2 Hetero-Nanostructures for Plasmon-Induced Enhancement of the Activity and Stability for Ethanol Electro-oxidation. AB - The catalytic electro-oxidation of ethanol is the essential technique for direct alcohol fuel cells (DAFCs) in the area of alternative energy for the ability of converting the chemical energy of alcohol into the electric energy directly. Developing highly efficient and stable electrode materials with antipoisoning ability for ethanol electro-oxidation remains a challenge. A highly ordered periodic Au-nanoparticle (NP)-decorated bilayer TiO2 nanotube (BTNT) heteronanostructure was fabricated by a two-step anodic oxidation of Ti foil and the subsequent photoreduction of HAuCl4. The plasmon-induced charge separation on the heterointerface of Au/TiO2 electrode enhances the electrocatalytic activity and stability for the ethanol oxidation under visible light irradiation. The highly ordered periodic heterostructure on the electrode surface enhanced the light harvesting and led to the greater performance of ethanol electro-oxidation under irradiation compared with the ordinary Au NPs-decorated monolayer TiO2 nanotube (MTNT). This novel Au/TiO2 electrode also performed a self-cleaning property under visible light attributed to the enhanced electro-oxidation of the adsorbed intermediates. This light-driven enhancement of the electrochemical performances provides a development strategy for the design and construction of DAFCs. PMID- 26863506 TI - Patterned Taping: A High-Efficiency Soft Lithographic Method for Universal Thin Film Patterning. AB - As a universal lithographic technique for microscale/nanoscale film patterns, we develop a strategy for the use of soft lithographically patterned pressure sensitive tape (patterned tape) as a pattern-transporting stamp material. Patterning was successfully implemented through the selective detachment and/or attachment of various thin films, including organic and metallic layers demanding no subsequent physical, thermal, or chemical treatment, as this incurs the risk of the deformation of the thin film and the deterioration of its functionalities. Its features of universal adhesion and flexibility enable pressure-sensitive tapes to form patterns on a variety of surfaces: organic, polymeric, and inorganic surfaces as well as flat, curved, uneven, and flexible substrates. Moreover, the proposed technique boasts the unique and distinct advantages of short operation time, supreme patterning yield, and multilayer stacking capability, which suggest considerable potential for their application to advanced optoelectronic device fabrication. PMID- 26863507 TI - Organohalide Perovskites for Solar Energy Conversion. AB - Lead-based organohalide perovskites have recently emerged as arguably the most promising of all next generation thin film solar cell technologies. Power conversion efficiencies have reached 20% in less than 5 years, and their application to other optoelectronic device platforms such as photodetectors and light emitting diodes is being increasingly reported. Organohalide perovskites can be solution processed or evaporated at low temperatures to form simple thin film photojunctions, thus delivering the potential for the holy grail of high efficiency, low embedded energy, and low cost photovoltaics. The initial device driven "perovskite fever" has more recently given way to efforts to better understand how these materials work in solar cells, and deeper elucidation of their structure-property relationships. In this Account, we focus on this element of organohalide perovskite chemistry and physics in particular examining critical electro-optical, morphological, and architectural phenomena. We first examine basic crystal and chemical structure, and how this impacts important solar-cell related properties such as the optical gap. We then turn to deeper electronic phenomena such as carrier mobilities, trap densities, and recombination dynamics, as well as examining ionic and dielectric properties and how these two types of physics impact each other. The issue of whether organohalide perovskites are predominantly nonexcitonic at room temperature is currently a matter of some debate, and we summarize the evidence for what appears to be the emerging field consensus: an exciton binding energy of order 10 meV. Having discussed the important basic chemistry and physics we turn to more device-related considerations including processing, morphology, architecture, thin film electro optics and interfacial energetics. These phenomena directly impact solar cell performance parameters such as open circuit voltage, short circuit current density, internal and external quantum efficiency, fill factor, and ultimately the all-important power conversion efficiency. Finally, we address the key challenges pertinent to actually delivering a new and viable solar cell technology. These include long-term cell stability, scaling to the module level, and the toxicity associated with lead. Organohalide perovskites not only offer exciting possibilities for next generation optoelectronics and photovoltaics, but are an intriguing class of material crossing the boundaries of molecular solids and banded inorganic semiconductors. This is a potential area of rich new chemistry, materials science, and physics. PMID- 26863511 TI - 3D-RISM-MP2 Approach to Hydration Structure of Pt(II) and Pd(II) Complexes: Unusual H-Ahead Mode vs Usual O-Ahead One. AB - Solvation of transition metal complexes with water has been one of the fundamental topics in physical and coordination chemistry. In particular, Pt(II) complexes have recently attracted considerable interest for their relation to anticancer activity in cisplatin and its analogues, yet the interaction of the water molecule and the metal center has been obscured. The challenge from a theoretical perspective remains that both the microscopic solvation effect and the dynamical electron correlation (DEC) effect have to be treated simultaneously in a reasonable manner. In this work we derive the analytical gradient for the three-dimensional reference interaction site model Moller-Plesset second order (3D-RISM-MP2) free energy. On the basis of the three-regions 3D-RISM self consistent field (SCF) method recently proposed by us, we apply a new layer of the Z-vector method to the CP-RISM equation as well as point-charge approximation to the derivatives with respect to the density matrix elements in the RISM-CPHF equation to remarkably reduce the computational cost. This method is applied to study the interaction of H2O with the d(8) square planar transition metal complexes in aqueous solution, trans-[Pt(II)Cl2(NH3)(glycine)] (1a), [Pt(II)(NH3)4](2+) (1b), [Pt(II)(CN)4](2-) (1c), and their Pd(II) analogues 2a, 2b, and 2c, respectively, to elucidate whether the usual H2O interaction through O atom (O-ahead mode) or unusual one through H atom (H-ahead mode) is stable in these complexes. We find that the interaction energy of the coordinating water and the transition metal complex changes little when switching from gas to aqueous phase, but the solvation free energy differs remarkably between the two interaction modes, thereby affecting the relative stability of the H-ahead and O ahead modes. Particularly, in contrast to the expectation that the O-ahead mode is preferred due to the presence of positive charges in 1b, the H-ahead mode is also found to be more stable. The O-ahead mode is found to be more stable than the H-ahead one only in 2b. The energy decomposition analysis (EDA) at the 3D RISM-MP2 level revealed that the O-ahead mode is stabilized by the electrostatic (ES) interaction, whereas the H-ahead one is mainly stabilized by the DEC effect. The ES interaction is also responsible for the difference between the Pd(II) and Pt(II) complexes; because the electrostatic potential is more negative along the z-axis in the Pt(II) complex than in the Pd(II) one, the O-ahead mode prefers the Pd(II) complexes, whereas the H-ahead becomes predominant in the Pt(II) complexes. PMID- 26863512 TI - Dimer-mediated cation diffusion in the stoichiometric ionic conductor Li3N. AB - Non-equilibrium molecular dynamics has been used to model cation diffusion in stoichiometric Li3N over the temperature range 50 < T/K < 800. The resulting diffusion coefficients are in excellent agreement with the available experimental data. We present a detailed atomistic account of the diffusion process. Contrary to the conclusions drawn from previous studies, our calculations show that it is unnecessary to invoke the presence of a small concentration of intrinsic defects in order to initiate diffusion. The structure can be considered to consist of alternating layers of composition Li2N and Li. As the temperature increases an increasing number of cations leave the Li2N layers and migrate either to the interlayer space or to the Li layer. Those that move into the interlayer space form Li2 dimers with cations in the Li2N layers and those that move into the neighboring layer form dimers with cations therein. The two types of dimer are aligned parallel and perpendicular to [001], respectively and have lifetimes of ~3 ps. The vacancies so created facilitate rapid diffusion in the Li2N layers and the interlayer cation motion results in slower diffusion perpendicular to the layers. PMID- 26863513 TI - The Value of Mentoring: An Interview with Rose Dobrof, DSW. PMID- 26863514 TI - Molecular Probe Optimization to Determine Cell Mortality in a Photosynthetic Organism (Microcystis aeruginosa) Using Flow Cytometry. AB - Microbial subpopulations in field and laboratory studies have been shown to display high heterogeneity in morphological and physiological parameters. Determining the real time state of a microbial cell goes beyond live or dead categories, as microbes can exist in a dormant state, whereby cell division and metabolic activities are reduced. Given the need for detection and quantification of microbes, flow cytometry (FCM) with molecular probes provides a rapid and accurate method to help determine overall population viability. By using SYTOX Green and SYTOX Orange in the model cyanobacteria Microcystis aeruginosa to detect membrane integrity, we develop a transferable method for rapid indication of single cell mortality. The molecular probes used within this journal will be referred to as green or orange nucleic acid probes respectively (although there are other products with similar excitation and emission wavelengths that have a comparable modes of action, we specifically refer to the fore mentioned probes). Protocols using molecular probes vary between species, differing principally in concentration and incubation times. Following this protocol set out on M.aeruginosa the green nucleic acid probe was optimized at concentrations of 0.5 uM after 30 min of incubation and the orange nucleic acid probe at 1 uM after 10 min. In both probes concentrations less than the stated optimal led to an under reporting of cells with membrane damage. Conversely, 5 uM concentrations and higher in both probes exhibited a type of non-specific staining, whereby 'live' cells produced a target fluorescence, leading to an over representation of 'non viable' cell numbers. The positive controls (heat-killed) provided testable dead biomass, although the appropriateness of control generation remains subject to debate. By demonstrating a logical sequence of steps for optimizing the green and orange nucleic acid probes we demonstrate how to create a protocol that can be used to analyse cyanobacterial physiological state effectively. PMID- 26863515 TI - Mutagenicity in a Molecule: Identification of Core Structural Features of Mutagenicity Using a Scaffold Analysis. AB - With advances in the development and application of Ames mutagenicity in silico prediction tools, the International Conference on Harmonisation (ICH) has amended its M7 guideline to reflect the use of such prediction models for the detection of mutagenic activity in early drug safety evaluation processes. Since current Ames mutagenicity prediction tools only focus on functional group alerts or side chain modifications of an analog series, these tools are unable to identify mutagenicity derived from core structures or specific scaffolds of a compound. In this study, a large collection of 6512 compounds are used to perform scaffold tree analysis. By relating different scaffolds on constructed scaffold trees with Ames mutagenicity, four major and one minor novel mutagenic groups of scaffold are identified. The recognized mutagenic groups of scaffold can serve as a guide for medicinal chemists to prevent the development of potentially mutagenic therapeutic agents in early drug design or development phases, by modifying the core structures of mutagenic compounds to form non-mutagenic compounds. In addition, five series of substructures are provided as recommendations, for direct modification of potentially mutagenic scaffolds to decrease associated mutagenic activities. PMID- 26863516 TI - Supporting read-across using biological data. AB - Read-across, i.e. filling toxicological data gaps by relating to similar chemicals, for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, however, biological similarity based on biological data adds extra strength to this process. In the context of developing Good Read-Across Practice guidance, a number of case studies were evaluated to demonstrate the use of biological data to enrich read-across. In the simplest case, chemically similar substances also show similar test results in relevant in vitro assays. This is a well-established method for the read-across of e.g. genotoxicity assays. Larger datasets of biological and toxicological properties of hundreds and thousands of substances become increasingly available enabling big data approaches in read-across studies. Several case studies using various big data sources are described in this paper. An example is given for the US EPA's ToxCast dataset allowing read across for high quality uterotrophic assays for estrogenic endocrine disruption. Similarly, an example for REACH registration data enhancing read-across for acute toxicity studies is given. A different approach is taken using omics data to establish biological similarity: Examples are given for stem cell models in vitro and short-term repeated dose studies in rats in vivo to support read-across and category formation. These preliminary biological data-driven read-across studies highlight the road to the new generation of read-across approaches that can be applied in chemical safety assessment. PMID- 26863517 TI - The Fraction of Cancer Attributable to Ways of Life, Infections, Occupation, and Environmental Agents in Brazil in 2020. AB - Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country. PMID- 26863518 TI - Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells. AB - The present study was conducted to determine the effects of 1-O acetylbritannilactone (ABL), a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF) signaling and angiogenesis in endothelial cells (ECs). We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day) recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis. PMID- 26863519 TI - Recognition of Frequency Modulated Whistle-Like Sounds by a Bottlenose Dolphin (Tursiops truncatus) and Humans with Transformations in Amplitude, Duration and Frequency. AB - Bottlenose dolphins (Tursiops truncatus) use the frequency contour of whistles produced by conspecifics for individual recognition. Here we tested a bottlenose dolphin's (Tursiops truncatus) ability to recognize frequency modulated whistle like sounds using a three alternative matching-to-sample paradigm. The dolphin was first trained to select a specific object (object A) in response to a specific sound (sound A) for a total of three object-sound associations. The sounds were then transformed by amplitude, duration, or frequency transposition while still preserving the frequency contour of each sound. For comparison purposes, 30 human participants completed an identical task with the same sounds, objects, and training procedure. The dolphin's ability to correctly match objects to sounds was robust to changes in amplitude with only a minor decrement in performance for short durations. The dolphin failed to recognize sounds that were frequency transposed by plus or minus 1/2 octaves. Human participants demonstrated robust recognition with all acoustic transformations. The results indicate that this dolphin's acoustic recognition of whistle-like sounds was constrained by absolute pitch. Unlike human speech, which varies considerably in average frequency, signature whistles are relatively stable in frequency, which may have selected for a whistle recognition system invariant to frequency transposition. PMID- 26863520 TI - Robot-Assisted Bladder Diverticulectomy with Concurrent Management of Bladder Outlet Obstruction. AB - INTRODUCTION: Robot-assisted bladder diverticulectomy (RABD) through a technique for easier identification of diverticulum along with concomitant management of bladder outlet obstruction (BOO) utilizing a combination of transurethral prostatectomy (TUR-P) and photoselective vaporization of prostate (PVP) is presented. MATERIALS AND METHODS: Between 2008 and 2015, 9 patients underwent RABD with concurrent treatment of BOO. Diverticula were identified by a technique of catheterizing the diverticulum and the bladder simultaneously and individually. RESULTS: Mean patient age was 62 +/- 9.8 and prostate volume was 70 +/- 26 ml. Mean time for endourological procedure was 77 +/- 35, mean console and total operative times were 108 +/- 38 and 186 +/- 56 min, respectively. Mean estimated blood loss was 71 +/- 37 ml. All diverticula were excised and BOO treated successfully. Bladder irrigation was not necessary in any patient. Mean hospitalization and catheter removal time was 5 +/- 3 and 8 +/- 3 days, respectively. No complications were observed. CONCLUSIONS: BOO is the main cause of acquired bladder diverticula and is largely due to benign prostatic hyperplasia. Concomitant performance of TUR-P and PVP along with RABD is feasible and safe. Individual catheterization of the diverticulum and bladder facilitates the identification of diverticulum even in the presence of multiple diverticula. PMID- 26863522 TI - Cobalt-Catalyzed Bis-alkynylation of Amides via Double C-H Bond Activation. AB - The first example of cobalt-catalyzed selective bis-alkynylation of amides via double C-H bond activation with the directing assistance of a removable bidentate auxiliary is reported. The developed alkynylation strategy is simple, efficient, and tolerant of various functional groups including ether, amine, halides, and heterocyclic motifs. The reaction can be scaled up under mild conditions. PMID- 26863521 TI - Metabolomic Profiles of Body Mass Index in the Framingham Heart Study Reveal Distinct Cardiometabolic Phenotypes. AB - BACKGROUND: Although obesity and cardiometabolic traits commonly overlap, underlying pathways remain incompletely defined. The association of metabolite profiles across multiple cardiometabolic traits may lend insights into the interaction of obesity and metabolic health. We sought to investigate metabolic signatures of obesity and related cardiometabolic traits in the community using broad-based metabolomic profiling. METHODS AND RESULTS: We evaluated the association of 217 assayed metabolites and cross-sectional as well as longitudinal changes in cardiometabolic traits among 2,383 Framingham Offspring cohort participants. Body mass index (BMI) was associated with 69 of 217 metabolites (P<0.00023 for all), including aromatic (tyrosine, phenylalanine) and branched chain amino acids (valine, isoleucine, leucine). Additional metabolic pathways associated with BMI included the citric acid cycle (isocitrate, alpha ketoglutarate, aconitate), the tryptophan pathway (kynurenine, kynurenic acid), and the urea cycle. There was considerable overlap in metabolite profiles between BMI, abdominal adiposity, insulin resistance [IR] and dyslipidemia, modest overlap of metabolite profiles between BMI and hyperglycemia, and little overlap with fasting glucose or elevated blood pressure. Metabolite profiles were associated with longitudinal changes in fasting glucose, but the involved metabolites (ornithine, 5-HIAA, aminoadipic acid, isoleucine, cotinine) were distinct from those associated with baseline glucose or other traits. Obesity status appeared to "modify" the association of 9 metabolites with IR. For example, bile acid metabolites were strongly associated with IR among obese but not lean individuals, whereas isoleucine had a stronger association with IR in lean individuals. CONCLUSIONS: In this large-scale metabolite profiling study, body mass index was associated with a broad range of metabolic alterations. Metabolite profiling highlighted considerable overlap with abdominal adiposity, insulin resistance, and dyslipidemia, but not with fasting glucose or blood pressure traits. PMID- 26863523 TI - Eyes on New Product Development. PMID- 26863524 TI - Non-steroidal anti-inflammatory drugs for chronic low back pain. AB - BACKGROUND: Chronic back pain is an important health problem. Non-steroidal anti inflammatory drugs (NSAIDs) are widely used to treat people with low back pain, especially people with acute back pain. Short term NSAID use is also recommended for pain relief in people with chronic back pain. Two types of NSAIDs are available and used to treat back pain: non-selective NSAIDs and selective COX-2 NSAIDs. In 2008, a Cochrane review identified a small but significant effect from NSAIDs compared to placebo in people with chronic back pain. This is an update of the Cochrane review published in 2008 and focuses on people with chronic low back pain. OBJECTIVES: To determine if NSAIDs are more efficacious than various comparison treatments for non-specific chronic low back pain and if so, which type of NSAID is most efficacious. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, PubMed and two clinical trials registry databases up to 24 June 2015 for randomized controlled trials (RCTs) published in English, German or Dutch. We also screened references cited in relevant reviews. SELECTION CRITERIA: We included RCTs (double-blind and single-blind) of NSAIDs used to treat people with chronic low back pain. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion in this Cochrane review according to the inclusion criteria. One review author extracted the data, and a second review author checked the data. Two review authors independently evaluated the risk of bias of all included trials. If data were clinically homogeneous, we performed a meta-analysis and assessed the quality of evidence using the GRADE approach. MAIN RESULTS: We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -3.30 (95% CI -5.33 to -1.27) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of -0.85 (95% CI 1.30 to -0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated.Two studies compared different types of non selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol.One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar. AUTHORS' CONCLUSIONS: Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use. PMID- 26863525 TI - Oxygen-Sensitive K+ Channels Modulate Human Chorionic Gonadotropin Secretion from Human Placental Trophoblast. AB - Human chorionic gonadotropin (hCG) is a key autocrine/paracrine regulator of placental syncytiotrophoblast, the transport epithelium of the human placenta. Syncytiotrophoblast hCG secretion is modulated by the partial pressure of oxygen (pO2), reactive oxygen species (ROS) and potassium (K+) channels. Here we test the hypothesis that K+ channels mediate the effects of pO2 and ROS on hCG secretion. Placental villous explants from normal term pregnancies were cultured for 6 days at 6% (normoxia), 21% (hyperoxia) or 1% (hypoxia) pO2. On days 3-5, explants were treated with 5mM 4-aminopyridine (4-AP) or tetraethylammonium (TEA), blockers of pO2-sensitive voltage-gated K+ (KV) channels, or ROS (10 1000MUM H2O2). hCG secretion and lactate dehydrogenase (LDH) release, a marker of necrosis, were determined daily. At day 6, hCG and LDH were measured in tissue lysate and 86Rb (K+) efflux assessed to estimate syncytiotrophoblast K+ permeability. hCG secretion and 86Rb efflux were significantly greater in explants maintained in 21% pO2 than normoxia. 4-AP/TEA inhibited hCG secretion to a greater extent at 21% than 6% and 1% pO2, and reduced 86Rb efflux at 21% but not 6% pO2. LDH release and tissue LDH/hCG were similar in 6%, 21% and 1% pO2 and unaffected by 4-AP/TEA. H2O2 stimulated 86Rb efflux and hCG secretion at normoxia but decreased 86Rb efflux, without affecting hCG secretion, at 21% pO2. 4-AP/TEA sensitive K+ channels participate in pO2-sensitive hCG secretion from syncytiotrophoblast. ROS effects on both hCG secretion and 86Rb efflux are pO2 dependent but causal links between the two remain to be established. PMID- 26863527 TI - Biochemical Comparison of Tpm1.1 (alpha) and Tpm2.2 (beta) Tropomyosins from Rabbit Skeletal Muscle. AB - Tpm1.1 (alpha) and Tpm2.2 (beta) tropomyosins (39 amino acid substitutions) were isolated from adult rabbit skeletal muscle without chemical modification of cysteine, with negligible phosphorylation as assessed by two-dimensional polyacrylamide gel electrophoresis, and characterized biochemically. Reconstituted skeletal thin filaments composed of Tpm2.2 produce ~30% less Ca(II) induced activation of the steady-state actomyosin-S1MgATPase rate than Tpm1.1 does. This is observed at a high S1/actin ratio (6 MUM myosin-S1A1, 3 MUM thin filaments, pCa 4) and as a function of pCa (0.3 MUM myosin-S1A1, 25 MUM thin filaments). The two pCa versus MgATPase relationships are similar in terms of their steepness and midpoint. Isotype has a bearing on self-polymerization and interaction with troponin. Solutions (pH 7, ionic strength of ~30 mM) of Tpm2.2 are more viscous than solutions of Tpm1.1, an observation explained by substitutions at the carboxy-terminal end of the molecule, including His276Asn and Met281Ile. Conversely, the enhancement of viscosity of Tpm1.1 by skeletal troponin is greater than that for Tpm2.2. Further, Tpm1.1 binds more strongly than Tpm2.2 to skeletal troponin-Sepharose, as evidenced by a later elution position in the salt gradient. Mixtures of tropomyosin and the amino-terminal CNBr fragment of troponin-T, CB1 (residues 1-151), were chromatographed on a size exclusion column in the presence of different concentrations of KCl. In 0.1 M salt, CB1 co-elutes with either isoform but is largely dissociated at 0.22 M. At intermediate salt concentrations, different degrees of complexation are observed, more extensive for Tpm1.1 than for Tpm2.2. Thus, the first reported variants of tropomyosin are distinct in their interactive and functional properties. The biochemical properties of Tpm2.2 are of particular relevance to the immature skeletal muscle thin filament. PMID- 26863526 TI - Human Liver Infection in a Dish: Easy-To-Build 3D Liver Models for Studying Microbial Infection. AB - Human liver infection is a major cause of death worldwide, but fundamental studies on infectious diseases affecting humans have been hampered by the lack of robust experimental models that accurately reproduce pathogen-host interactions in an environment relevant for the human disease. In the case of liver infection, one consequence of this absence of relevant models is a lack of understanding of how pathogens cross the sinusoidal endothelial barrier and parenchyma. To fill that gap we elaborated human 3D liver in vitro models, composed of human liver sinusoidal endothelial cells (LSEC) and Huh-7 hepatoma cells as hepatocyte model, layered in a structure mimicking the hepatic sinusoid, which enable studies of key features of early steps of hepatic infection. Built with established cell lines and scaffold, these models provide a reproducible and easy-to-build cell culture approach of reduced complexity compared to animal models, while preserving higher physiological relevance compared to standard 2D systems. For proof-of-principle we challenged the models with two hepatotropic pathogens: the parasitic amoeba Entamoeba histolytica and hepatitis B virus (HBV). We constructed four distinct setups dedicated to investigating specific aspects of hepatic invasion: 1) pathogen 3D migration towards hepatocytes, 2) hepatocyte barrier crossing, 3) LSEC and subsequent hepatocyte crossing, and 4) quantification of human hepatic virus replication (HBV). Our methods comprise automated quantification of E. histolytica migration and hepatic cells layer crossing in the 3D liver models. Moreover, replication of HBV virus occurs in our virus infection 3D liver model, indicating that routine in vitro assays using HBV or others viruses can be performed in this easy-to-build but more physiological hepatic environment. These results illustrate that our new 3D liver infection models are simple but effective, enabling new investigations on infectious disease mechanisms. The better understanding of these mechanisms in a human relevant environment could aid the discovery of drugs against pathogenic liver infection. PMID- 26863528 TI - Three-dimensional modeling of flow and deformation in idealized mild and moderate arterial vessels. AB - Three-dimensional numerical calculations of mild and moderate stenosed blood vessels have been performed. Large eddy simulation through a dynamic subgrid scale Smagorinsky model is applied to model the transitional and turbulent pulsatile flow. For the compliant stenosed model, fluid-structure interaction is realized through a two-way coupling between the fluid flow and the deforming vessel through the change in the external diameter due to the increment of circumferential pressure via a novel moving boundary approach. Model predictions compare very well against measured and numerical data for the centerline velocities, thickness of the flow separation zones and radial wall displacements. PMID- 26863529 TI - Single-Molecule Stochastic Analysis of Channeling Enzyme Tryptophan Synthase. AB - The channeling enzyme tryptophan synthase provides a paradigmatic example of a chemical nanomachine. It possesses two active centers and, as a single molecule, catalyzes 13 different reaction steps with a complex pattern of allosteric regulation and with an intermediate product channeled from one active center to another. Here, the first single-molecule stochastic model of the enzyme is proposed and analyzed. All its transition rate constants were deduced from the experimental data available, and no fitting parameters were thus employed. Numerical simulations reveal strong correlations in the states of the active centers and the emergent synchronization of intramolecular processes in tryptophan synthase. PMID- 26863530 TI - The stunted child with an overweight mother as a growing public health concern in resource-poor environments: a case study from Guatemala. AB - BACKGROUND: Overweight and obesity are emerging at alarming rates in low income women in many countries. Guatemala has the additional burden of a high prevalence of chronic under-nutrition (stunting) in children. AIM: The purpose of this paper is to explore the dual burden of infant and child (5-23 months) under-nutrition and maternal over-weight and obesity in the Western Highlands of Guatemala. SUBJECTS AND METHODS: Anthropometric measures were collected in 446 mother-infant dyads in a metropolitan population of mixed indigenous (Maya) and non-indigenous descent in the Western Highlands of Guatemala. Children were identified as stunted based on a height for age <-2 below the WHO reference median and maternal overweight/obesity defined as a BMI >=25. Stunted children with an overweight/obese mother were compared to other children who were not stunted and/or who did not have an overweight/obese mother. RESULTS: The prevalences of stunting (38%) and maternal overweight/obesity (45%) were high, but just 17% of the mother and child pairs were dual burden. The socio-demographic characteristics of stunted children were not influenced by maternal overweight or obesity. CONCLUSION: Policies are needed to address under-nutrition as well as preventing obesity and obesity-related chronic disease risks of stunted children and their mothers. PMID- 26863531 TI - Perceiving Object Shape from Specular Highlight Deformation, Boundary Contour Deformation, and Active Haptic Manipulation. AB - It is well known that motion facilitates the visual perception of solid object shape, particularly when surface texture or other identifiable features (e.g., corners) are present. Conventional models of structure-from-motion require the presence of texture or identifiable object features in order to recover 3-D structure. Is the facilitation in 3-D shape perception similar in magnitude when surface texture is absent? On any given trial in the current experiments, participants were presented with a single randomly-selected solid object (bell pepper or randomly-shaped "glaven") for 12 seconds and were required to indicate which of 12 (for bell peppers) or 8 (for glavens) simultaneously visible objects possessed the same shape. The initial single object's shape was defined either by boundary contours alone (i.e., presented as a silhouette), specular highlights alone, specular highlights combined with boundary contours, or texture. In addition, there was a haptic condition: in this condition, the participants haptically explored with both hands (but could not see) the initial single object for 12 seconds; they then performed the same shape-matching task used in the visual conditions. For both the visual and haptic conditions, motion (rotation in depth or active object manipulation) was present in half of the trials and was not present for the remaining trials. The effect of motion was quantitatively similar for all of the visual and haptic conditions-e.g., the participants' performance in Experiment 1 was 93.5 percent higher in the motion or active haptic manipulation conditions (when compared to the static conditions). The current results demonstrate that deforming specular highlights or boundary contours facilitate 3-D shape perception as much as the motion of objects that possess texture. The current results also indicate that the improvement with motion that occurs for haptics is similar in magnitude to that which occurs for vision. PMID- 26863532 TI - Factors Affecting Diet Variation in the Pyrenean Rock Ptarmigan (Lagopus muta pyrenaica): Conservation Implications. AB - The Pyrenean rock ptarmigan (Lagopus muta pyrenaica) lives at one of the southernmost limits of the ptarmigan range. Their small population sizes and the impacts of global changes are limiting factors in the conservation of this threatened subspecies. An effective conservation policy requires precise basic knowledge of a species' food and habitat requirements, information that is practically non-existent for this Pyrenean population. Here, we describe the diet of a ptarmigan population in the Eastern Pyrenees, the environmental factors influencing its variability and the relationship between diet floristic composition and quality. Diet composition was determined by microhistological analysis of faeces and diet quality was estimated from free-urate faecal N content. Our results show that grouse diet is based mainly on arctic-alpine shrubs of the Ericaceae family, as well as dwarf willows (Salix spp.) and Dryas octopetala. The most frequently consumed plant species was Rhododendron ferrugineum, but its abundance in the diet was negatively related to the diet nitrogen content. Conversely, the abundance of Salix spp., grass leaves and arthropods increased the nitrogen content of the diet. Seasonality associated with snow-melting contributed the most to variability in the Pyrenean ptarmigan diet, differentiating winter from spring/summer diets. The latter was characterised by a high consumption of dwarf willows, flowers, arthropods and tender forb leaves. Geographic area and sex-age class influenced diet variability to a lesser extent. Current temperature increases in the Pyrenees due to global warming may reduce the persistence and surface area of snow-packs where preferred plants for rock ptarmigan usually grow, thus reducing food availability. The high consumption of Rh. ferrugineum characterised the diet of the Pyrenean population. Given the toxicity of this plant for most herbivores, its potential negative effect on Pyrenean ptarmigan populations should be evaluated. PMID- 26863533 TI - Potentiation of DeltaF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines. AB - The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, DeltaF508). Misfolding of DeltaF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of DeltaF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for DeltaF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value <10 MUM. Among the compounds, 7q (a novel CFTR potentiator, CP7q) showed the highest potentiation activity with EC50 values of 0.88 +/- 0.11 and 4.45 +/- 0.31 MUM for wild-type and DeltaF508-CFTR, respectively. In addition, CP7q significantly potentiated chloride conductance of G551D-CFTR, a CFTR gating mutant; its maximal potentiation activity was 1.9 fold higher than the well-known CFTR potentiator genistein. Combination treatment with CP7q and VX-809, a corrector of DeltaF508-CFTR, significantly enhanced functional rescue of DeltaF508-CFTR compared with VX-809 alone. CP7q did not alter the cytosolic cAMP level and showed no cytotoxicity at the concentration showing maximum efficacy. The hydroxypyrazolines may be potential development candidates for drug therapy of cystic fibrosis. PMID- 26863534 TI - Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series. AB - BACKGROUND: Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS. METHODS: A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality. RESULTS: Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1). CONCLUSION: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity. PMID- 26863536 TI - Breakdown of Inter-Hemispheric Connectivity Is Associated with Posttraumatic Symptomatology and Memory Impairment. AB - Altered brain anatomy in specific gray-matter regions has been shown in patients with posttraumatic stress disorder (PTSD). Recently, white-matter tracts have become a focus of research in PTSD. The corpus callosum (CC) is the principal white-matter fiber bundle, crucial in relaying sensory, motor and cognitive information between hemispheres. Alterations in CC fibers have been reported in PTSD and might be assumed to underlie substantial behavioral and cognitive sequelae; however most diffusion tensor imaging (DTI) studies in adult-onset PTSD failed to address the clinical correlates between imaging and PTSD symptoms severity, behavioral manifestation and cognitive functions. In the current study we examined (a) to what extent microstructural integrity of the CC is associated with memory performance and (b) whether imaging and cognitive parameters are associated with PTSD symptom severity. DTI data were obtained and fractional anisotropy (FA) values were computed for 16 patients and 14 controls. PTSD symptom severity was assessed by employing the clinician administered PTSD scale (CAPS) and memory was tested using a task probing item and associative memory for words and pictures. Significant correlations were found between PTSD symptoms severity, memory accuracy and reaction-time to CC FA values in the PTSD group. This study demonstrates meaningful clinical and cognitive correlates of microstructural connectivity. These results have implications for diagnostic tools and future studies aimed at identifying individuals at risk for PTSD. PMID- 26863535 TI - Simvastatin Sodium Salt and Fluvastatin Interact with Human Gap Junction Gamma-3 Protein. AB - Finding pleiomorphic targets for drugs allows new indications or warnings for treatment to be identified. As test of concept, we applied a new chemical genomics approach to uncover additional targets for the widely prescribed lipid lowering pro-drug simvastatin. We used mRNA extracted from internal mammary artery from patients undergoing coronary artery surgery to prepare a viral cardiovascular protein library, using T7 bacteriophage. We then studied interactions of clones of the bacteriophage, each expressing a different cardiovascular polypeptide, with surface-bound simvastatin in 96-well plates. To maximise likelihood of identifying meaningful interactions between simvastatin and vascular peptides, we used a validated photo-immobilisation method to apply a series of different chemical linkers to bind simvastatin so as to present multiple orientations of its constituent components to potential targets. Three rounds of biopanning identified consistent interaction with the clone expressing part of the gene GJC3, which maps to Homo sapiens chromosome 7, and codes for gap junction gamma-3 protein, also known as connexin 30.2/31.3 (mouse connexin Cx29). Further analysis indicated the binding site to be for the N-terminal domain putatively 'regulating' connexin hemichannel and gap junction pores. Using immunohistochemistry we found connexin 30.2/31.3 to be present in samples of artery similar to those used to prepare the bacteriophage library. Surface plasmon resonance revealed that a 25 amino acid synthetic peptide representing the discovered N-terminus did not interact with simvastatin lactone, but did bind to the hydrolysed HMG CoA inhibitor, simvastatin acid. This interaction was also seen for fluvastatin. The gap junction blockers carbenoxolone and flufenamic acid also interacted with the same peptide providing insight into potential site of binding. These findings raise key questions about the functional significance of GJC3 transcripts in the vasculature and other tissues, and this connexin's role in therapeutic and adverse effects of statins in a range of disease states. PMID- 26863538 TI - Low Predictability of Colour Polymorphism in Introduced Guppy (Poecilia reticulata) Populations in Panama. AB - Colour polymorphism is a recurrent feature of natural populations, and its maintenance has been studied in a range of taxa in their native ranges. However, less is known about whether (and how) colour polymorphism is maintained when populations are removed from their native environments, as in the case of introduced species. We here address this issue by analyzing variation in colour patterns in recently-discovered introduced populations of the guppy (Poecilia reticulata) in Panama. Specifically, we use classic colour analysis to estimate variation in the number and the relative area of different colour spots across low predation sites in the introduced Panamanian range of the species. We then compare this variation to that found in the native range of the species under low and high predation regimes. We found aspects of the colour pattern that were both consistent and inconsistent with the classical paradigm of colour evolution in guppies. On one hand, the same colours that dominated in native populations (orange, iridescent and black) were also the most dominant in the introduced populations in Panama. On the other, there were no clear differences between either introduced-low and native low- and high predation populations. Our results are therefore only partially consistent with the traditional role of female preference in the absence of predators, and suggest that additional factors could influence colour patterns when populations are removed from their native environments. Future research on the interaction between female preference and environmental variability (e.g. multifarious selection), could help understand adaptive variation in this widely-introduced species, and the contexts under which variation in adaptive traits parallels (or not) variation in the native range. PMID- 26863539 TI - Allergen-Specific Immunotherapy Alters the Frequency, as well as the FcR and CLR Expression Profiles of Human Dendritic Cell Subsets. AB - Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcepsilonRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance. PMID- 26863540 TI - Greed and Fear in Network Reciprocity: Implications for Cooperation among Organizations. AB - Extensive interdisciplinary literatures have built on the seminal spatial dilemmas model, which depicts the evolution of cooperation on regular lattices, with strategies propagating locally by relative fitness. In this model agents may cooperate with neighbors, paying an individual cost to enhance their collective welfare, or they may exploit cooperative neighbors and diminish collective welfare. Recent research has extended the model in numerous ways, incorporating behavioral noise, implementing other network topologies or adaptive networks, and employing alternative dynamics of replication. Although the underlying dilemma arises from two distinct dimensions-the gains for exploiting cooperative partners (Greed) and the cost of cooperating with exploitative partners (Fear)-most work following from the spatial dilemmas model has argued or assumed that the dilemma can be represented with a single parameter: This research has typically examined Greed or Fear in isolation, or a composite such as the K-index of Cooperation or the ratio of the benefit to cost of cooperation. We challenge this claim on theoretical grounds-showing that embedding interaction in networks generally leads Greed and Fear to have divergent, interactive, and highly nonlinear effects on cooperation at the macro level, even when individuals respond identically to Greed and Fear. Using computational experiments, we characterize both dynamic local behavior and long run outcomes across regions of this space. We also simulate interventions to investigate changes of Greed and Fear over time, showing how model behavior changes asymmetrically as boundaries in payoff space are crossed, leading some interventions to have irreversible effects on cooperation. We then replicate our experiments on inter-organizational network data derived from links through shared directors among 2,400 large US corporations, thus demonstrating our findings for Greed and Fear on a naturally occurring network. In closing, we discuss implications of our main findings regarding Greed and Fear for the problem of cooperation on inter-organizational networks. PMID- 26863541 TI - Viral Replication Protein Inhibits Cellular Cofilin Actin Depolymerization Factor to Regulate the Actin Network and Promote Viral Replicase Assembly. AB - RNA viruses exploit host cells by co-opting host factors and lipids and escaping host antiviral responses. Previous genome-wide screens with Tomato bushy stunt virus (TBSV) in the model host yeast have identified 18 cellular genes that are part of the actin network. In this paper, we show that the p33 viral replication factor interacts with the cellular cofilin (Cof1p), which is an actin depolymerization factor. Using temperature-sensitive (ts) Cof1p or actin (Act1p) mutants at a semi-permissive temperature, we find an increased level of TBSV RNA accumulation in yeast cells and elevated in vitro activity of the tombusvirus replicase. We show that the large p33 containing replication organelle-like structures are located in the close vicinity of actin patches in yeast cells or around actin cable hubs in infected plant cells. Therefore, the actin filaments could be involved in VRC assembly and the formation of large viral replication compartments containing many individual VRCs. Moreover, we show that the actin network affects the recruitment of viral and cellular components, including oxysterol binding proteins and VAP proteins to form membrane contact sites for efficient transfer of sterols to the sites of replication. Altogether, the emerging picture is that TBSV, via direct interaction between the p33 replication protein and Cof1p, controls cofilin activities to obstruct the dynamic actin network that leads to efficient subversion of cellular factors for pro-viral functions. In summary, the discovery that TBSV interacts with cellular cofilin and blocks the severing of existing filaments and the formation of new actin filaments in infected cells opens a new window to unravel the way by which viruses could subvert/co-opt cellular proteins and lipids. By regulating the functions of cofilin and the actin network, which are central nodes in cellular pathways, viruses could gain supremacy in subversion of cellular factors for pro viral functions. PMID- 26863543 TI - Edesign: Primer and Enhanced Internal Probe Design Tool for Quantitative PCR Experiments and Genotyping Assays. AB - Analytical PCR experiments preferably use internal probes for monitoring the amplification reaction and specific detection of the amplicon. Such internal probes have to be designed in close context with the amplification primers, and may require additional considerations for the detection of genetic variations. Here we describe Edesign, a new online and stand-alone tool for designing sets of PCR primers together with an internal probe for conducting quantitative real-time PCR (qPCR) and genotypic experiments. Edesign can be used for selecting standard DNA oligonucleotides like for instance TaqMan probes, but has been further extended with new functions and enhanced design features for Eprobes. Eprobes, with their single thiazole orange-labelled nucleotide, allow for highly sensitive genotypic assays because of their higher DNA binding affinity as compared to standard DNA oligonucleotides. Using new thermodynamic parameters, Edesign considers unique features of Eprobes during primer and probe design for establishing qPCR experiments and genotyping by melting curve analysis. Additional functions in Edesign allow probe design for effective discrimination between wild-type sequences and genetic variations either using standard DNA oligonucleotides or Eprobes. Edesign can be freely accessed online at http://www.dnaform.com/edesign2/, and the source code is available for download. PMID- 26863542 TI - Comparative Transcriptomic Exploration Reveals Unique Molecular Adaptations of Neuropathogenic Trichobilharzia to Invade and Parasitize Its Avian Definitive Host. AB - To date, most molecular investigations of schistosomatids have focused principally on blood flukes (schistosomes) of humans. Despite the clinical importance of cercarial dermatitis in humans caused by Trichobilharzia regenti and the serious neuropathologic disease that this parasite causes in its permissive avian hosts and accidental mammalian hosts, almost nothing is known about the molecular aspects of how this fluke invades its hosts, migrates in host tissues and how it interacts with its hosts' immune system. Here, we explored selected aspects using a transcriptomic-bioinformatic approach. To do this, we sequenced, assembled and annotated the transcriptome representing two consecutive life stages (cercariae and schistosomula) of T. regenti involved in the first phases of infection of the avian host. We identified key biological and metabolic pathways specific to each of these two developmental stages and also undertook comparative analyses using data available for taxonomically related blood flukes of the genus Schistosoma. Detailed comparative analyses revealed the unique involvement of carbohydrate metabolism, translation and amino acid metabolism, and calcium in T. regenti cercariae during their invasion and in growth and development, as well as the roles of cell adhesion molecules, microaerobic metabolism (citrate cycle and oxidative phosphorylation), peptidases (cathepsins) and other histolytic and lysozomal proteins in schistosomula during their particular migration in neural tissues of the avian host. In conclusion, the present transcriptomic exploration provides new and significant insights into the molecular biology of T. regenti, which should underpin future genomic and proteomic investigations of T. regenti and, importantly, provides a useful starting point for a range of comparative studies of schistosomatids and other trematodes. PMID- 26863544 TI - Developing a Referral Protocol for Community-Based Occupational Therapy Services in Taiwan: A Logistic Regression Analysis. AB - Because resources for long-term care services are limited, timely and appropriate referral for rehabilitation services is critical for optimizing clients' functions and successfully integrating them into the community. We investigated which client characteristics are most relevant in predicting Taiwan's community based occupational therapy (OT) service referral based on experts' beliefs. Data were collected in face-to-face interviews using the Multidimensional Assessment Instrument (MDAI). Community-dwelling participants (n = 221) >= 18 years old who reported disabilities in the previous National Survey of Long-term Care Needs in Taiwan were enrolled. The standard for referral was the judgment and agreement of two experienced occupational therapists who reviewed the results of the MDAI. Logistic regressions and Generalized Additive Models were used for analysis. Two predictive models were proposed, one using basic activities of daily living (BADLs) and one using instrumental ADLs (IADLs). Dementia, psychiatric disorders, cognitive impairment, joint range-of-motion limitations, fear of falling, behavioral or emotional problems, expressive deficits (in the BADL-based model), and limitations in IADLs or BADLs were significantly correlated with the need for referral. Both models showed high area under the curve (AUC) values on receiver operating curve testing (AUC = 0.977 and 0.972, respectively). The probability of being referred for community OT services was calculated using the referral algorithm. The referral protocol facilitated communication between healthcare professionals to make appropriate decisions for OT referrals. The methods and findings should be useful for developing referral protocols for other long-term care services. PMID- 26863545 TI - ISART: A Generic Framework for Searching Books with Social Information. AB - Effective book search has been discussed for decades and is still future-proof in areas as diverse as computer science, informatics, e-commerce and even culture and arts. A variety of social information contents (e.g, ratings, tags and reviews) emerge with the huge number of books on the Web, but how they are utilized for searching and finding books is seldom investigated. Here we develop an Integrated Search And Recommendation Technology (IsArt), which breaks new ground by providing a generic framework for searching books with rich social information. IsArt comprises a search engine to rank books with book contents and professional metadata, a Generalized Content-based Filtering model to thereafter rerank books with user-generated social contents, and a learning-to-rank technique to finally combine a wide range of diverse reranking results. Experiments show that this technology permits embedding social information to promote book search effectiveness, and IsArt, by making use of it, has the best performance on CLEF/INEX Social Book Search Evaluation datasets of all 4 years (from 2011 to 2014), compared with some other state-of-the-art methods. PMID- 26863546 TI - Asymmetric Catalysis Powered by Chiral Cyclopentadienyl Ligands. AB - Application of chiral derivatives of the versatile and ubiquitous cyclopentadienyl ligand has long remained an underdeveloped area in asymmetric catalysis. In this Perspective we highlight recent exciting results that demonstrate their enormous potential. In particular, we provide a comparative analysis of the available ligand families, an overview of their complexation chemistry, and an examination of their application in catalytic enantioselective reactions. We also discuss current limitations and speculate on the developments that are necessary to advance the field further. PMID- 26863547 TI - Gene Expression Profiling of Infecting Microbes Using a Digital Bar-coding Platform. AB - For most mammalian pathogens, gene expression profiling studies have been limited by technical difficulties to accurately quantify pathogen gene transcripts from infected tissues. Pathogen RNA constitutes a tiny portion of the total RNA isolated from infected tissue samples. Both microarray and RNAseq technologies have difficulties in generating reliable reads for weakly expressed pathogen genes. Mutant pathogen strains with reduced in vivo proliferation pose an even bigger challenge. Here we describe an in vivo gene expression profiling protocol that is very fast, extremely sensitive and highly reproducible. We developed this protocol during our investigation of the fungal pathogen Candida albicans in a murine model of hematogenously disseminated candidiasis. Using this protocol, we have documented time courses of dynamically regulated C. albicans gene expression during kidney infection, and discovered unexpected features of gene expression responses to antifungal drug treatment in vivo. PMID- 26863548 TI - Sample preparation protocol for bottom-up proteomic analysis of the secretome of the islets of Langerhans. AB - We evaluate a set of protocols for preparation of the secretome from murine islets of Langerhans for bottom-up proteomic analysis. Of the protocols evaluated, a filter-aided sample preparation based approach using sodium dodecyl sulfate as a detergent to solubilize proteins generated the most protein identifications. A total of 362 protein groups (average of 3.7 peptides/protein) were identified from the secretome using the SDS-FASP protocol; a combination of data from three protocols generated 413 protein group identifications. As expected, the identified proteins included insulin 1 and 2, somatostatin, and glucagon, the four main secreted components from islets. STRING network analysis classified the other proteins as being associated with extracellular exosomes, membrane-bounded vesicles, vesicles, and the extracellular region. PMID- 26863549 TI - The Fight for the Elimination of Racial and Ethnic Health Disparities: Acknowledging the Work and Celebrating the Life of Mr. Louis Stokes. AB - The elimination of health disparities based upon race and ethnicity is a long road. The Honorable Louis Stokes was an indefatigable champion of the underserved who worked to create a world where the vision of health equity would not be a catchphrase but a reality. PMID- 26863550 TI - Life Expectancy Varies in Local Communities in Chicago: Racial and Spatial Disparities and Correlates. AB - OBJECTIVES: Life expectancy in the USA reached a record high of 78.7 years in 2010. However, the racial gap in life expectancy persists. National data, which are readily available, provide averages which mask important local-level differences. Local data are needed to identify the worst off groups, key to reducing disparities and pursuing health equity. METHODS: Using vital records data, we calculated life expectancy for the USA and Chicago by race/ethnicity and gender and for Chicago's 77 community areas. We also examined the correlation between life expectancy and (1) racial/ethnic composition of a community area and (2) median household income. RESULTS: In Chicago, the highest life expectancy was observed among Hispanics at 84.6 and the lowest life expectancy was observed among Blacks at 71.7-a difference of about 13 years. Life expectancy varied substantially across the 77 community areas of Chicago, from a low of 68.2 to a high of 83.3-a difference of 15 years. There were strong correlations between life expectancy and the racial, ethnic, and socioeconomic distributions among the community areas. CONCLUSIONS: The examination of data at the local level provides invaluable insight into which communities are facing the greatest burden in terms of health and well-being. It is only through the examination of local-level data that we can understand the unique needs of these communities and begin to address them. PMID- 26863551 TI - Effects of Perceived Discrimination and Length of Residency on the Health of Foreign-Born Populations. AB - This study explores the relationship between chronic conditions, perceived discrimination, and length of residency among three racial groups of foreign-born respondents: Afro-Caribbean, Asian, and Latino Americans. Analysis utilized Collaborative Psychiatric Epidemiology Surveys (CPES) merged data from the National Latino and Asian American Study (NLAAS) and the National Survey of American Life (NSAL). Afro-Caribbean subgroups were more likely than Asian and Latino American subgroups to report perceived discrimination. Logistic regression analysis was conducted to determine which groups within the model were more likely to report chronic health conditions. Perceived discrimination was found to vary by race and was inversely associated with chronic respiratory conditions for Afro-Caribbeans. In general, years of US residency were associated with health across all chronic conditions where those in the USA longer were more likely to experience health-related problems. Perceived discrimination revealed mixed results. PMID- 26863552 TI - Mental Health Disparities Among Low-Income US Hispanic Residents of a US-Mexico Border Colonia. AB - Unregulated residential settlements along the US side of the US-Mexico border, often called "colonias", are mainly populated by low-income Mexican-origin Hispanics. Colonia residents face numerous social, environmental, economic and public health challenges. Despite this, the mental health of individuals living in colonias has remained largely understudied. Drawing from a survey (N = 98) conducted through a community-based participatory research project in one colonia suffering from numerous environmental and social challenges, this study analyzes residents' mental health outcomes and access to mental health care with a focus on intra-ethnic disparities based on environmental concerns, nativity, language acculturation, comorbidity, gender, health insurance, and stressful life events. Data were analyzed using descriptive statistics, correlation, and regression. More than one third of the residents have been diagnosed with a mental health condition and over half reported stress and excess worry. In terms of mental health care, 77 % of individuals diagnosed with a mental health problem have sought additional help mainly through a primary care provider despite the high levels of uninsured individuals. Comorbidity, being female, recent negative life events, and high levels of environmental concerns were significant predictors of negative mental health outcomes. This study contributes to the understanding of the complex health dynamics of the US Hispanic population. It also highlights the need for additional research and resources devoted to the mental health of low income minorities in isolated communities. PMID- 26863553 TI - Colorectal Cancer Screening among Chinese, Cambodian, and Vietnamese Immigrants in Chicago. AB - Asian Americans are now the most rapidly growing minority group in the USA. Over 60 % of Asian Americans in the USA are immigrants. Cancer has been the leading cause of death among Asian Americans since 1980. Understanding the barriers to screening is essential to reduce the unnecessary burden of cancer. Little is known about colorectal cancer screening behavior among foreign-born Asian Americans and how socio-demographic factors may influence the behavior. Even less is known about disaggregated Asian subgroups. Using data from the Chicago Asian Community Survey, a local health assessment survey of three Asian subgroups in Chicago, Chinese, Cambodian, and Vietnamese, this study found that the colorectal cancer screening rate were much lower among foreign-born Asian Americans in Chicago (30 %) than the national rate for the general population (59 %). Furthermore, we studied disaggregated data to determine colorectal cancer screening differences between communities. Findings from this study provide a critical evidence base to inform future research and intervention designs. PMID- 26863554 TI - Gender and Ethnic Differences in the Association Between Obesity and Depression Among Black Adolescents. AB - AIM: This study aimed to investigate the association between obesity and major depression disorder (MDD) in a nationally representative sample of Black adolescents in the USA. The study also tested the effects of ethnicity and gender as possible moderators. METHOD: Data came from the National Survey of American Life (NSAL)-Adolescents, a representative household mental health survey of Black adolescents in the USA. Participants consisted of 1170 Black adolescents (810 African Americans and 360 Caribbean Blacks). Obesity was defined determined by the cutoff points based on the body mass index (BMI) appropriate for age and gender. Twelve-month MDD was measured using the World Mental Health Composite International Diagnostic Interview (CIDI). In the first step, the association between obesity and MDD in the pooled sample, controlling for the main effects of gender and ethnicity. In the next steps, two interactions were tested: (1) obesity and ethnicity and (2) obesity and gender. RESULTS: Although any associations between obesity and MDD in the pooled sample of Blacks were not found, there was a significant interaction between ethnicity and obesity on MDD. Upon testing the associations across intersections of ethnicity and gender, a positive association was found among Caribbean Black females but not Caribbean Black males, African American males, or African American female. CONCLUSION: The link between BMI and MDD among Blacks depends on ethnicity and gender, and risk of comorbid depression among Black youth with obesity is highest among Caribbean Black females. PMID- 26863555 TI - Sociodemographic Correlates of Dietary Practices among Asian-Americans: Results from the California Health Interview Survey. AB - OBJECTIVE: Studies show that Asian-American subgroups do not always meet dietary recommendations and are at high risk of cardiovascular diseases. The purpose of our research is to illustrate the various sociodemographic correlates of dietary habits for six subgroups of Asian-Americans in California. DESIGN: The 2005 California Health Interview Survey (CHIS) was utilized. A total of 3772 Asian Americans were included in this study, with the largest subgroup being Chinese (n = 1280; N = 913,798). The outcome variable for this study was dietary behavior defined as consuming five or more fruits and vegetables per day (5-a-day), provided by CHIS. Univariate and multivariable regression analyses were conducted accounting for complex survey design. RESULTS: Being a female (Chinese, Filipina, Korean, and Vietnamese), not being married (Chinese), not being a college graduate (Chinese), living in poverty (South Asian), and speaking only English language at home (Chinese and Japanese) were associated with higher odds of not meeting a 5-a-day requirement. CONCLUSION: Results highlighted several sociodemographic correlates to not meeting 5-a-day requirement among six Asian American subgroups. Targeted health promotion measures for such at-risk groups should be implemented to improve dietary practices. PMID- 26863556 TI - Maternal Health Status and Parenting Stress in Low-Income, Ethnic-Minority Mothers of Children with Conduct Disorder Problems: the Role of Daily Parenting Hassles. AB - OBJECTIVES: Minimal attention has been given to understanding parenting stress among low-income, ethnically diverse mothers of children with conduct problems. Maternal health and parenting hassles may serve as important risk factors for parenting stress. This study examined whether parenting hassles mediated the relations between maternal physical and mental health and parenting stress in a sample of low-income, ethnically diverse mothers of children with behavioral problems. METHODS: The sample included 177 low-income black, Latina, and white mothers of kindergartners with behavior problems. Path analysis was employed to assess the associations between maternal mental and physical health and parenting stress, as well as the moderating role of parenting hassles in this cross sectional study. RESULTS: After adjusting for covariates, we found that parenting hassles mediated the relationship between social support and parenting stress as well as maternal health and parenting stress. CONCLUSION: Findings suggest that promoting coping resources for daily parenting hassles and supporting the physical and mental health of minority mothers may have important implications for parenting children with high behavior problems. PMID- 26863557 TI - Risk of Gestational Diabetes Among South Asian Immigrants Living in New Jersey--a Retrospective Data Review. AB - BACKGROUND: We aimed to identify differences in distribution of risk factors, prevalence, and complications of gestational diabetes (GD) among South Asian (SA) immigrant women, separately for immigrants from India, Bangladesh, Pakistan, and Sri Lanka, relative to US-born non-Hispanic whites (NHW) living in New Jersey. METHOD: We used NJ birth certificate data linked to hospitalization data from 1999 to 2002 (n = 327,069). We compared the distribution of risk factors among these groups using chi-squared test and calculated adjusted odds of GD for SA groups compared to NHW using logistic regression. Among women with GD, we further analyzed the odds of complications for SA groups relative to whites. RESULTS: Sri Lankans were more likely to be of advanced maternal age. Pakistanis and Bangladeshis were more likely to start prenatal care late. Bangladeshis had the highest adjusted odds of GD (aOR = 4.3; 95 % confidence interval (CI) 3.5-5.3), followed by Indians (aOR = 3.9; 95 % CI 3.7-4.2), Sri Lankans (aOR = 3.6; 95 % CI 2.4-5.8), and Pakistanis (aOR = 3.4; 95 % CI 2.9-3.8) relative to NHW. Among women with GD, South Asian groups had lower odds of preterm birth and higher odds of having a small for gestational age infant than whites. DISCUSSION: This study provided evidence of disproportionate risk of GD among four SA groups living in NJ. PMID- 26863559 TI - Racial and Ethnic Disparities in Adverse Drug Events: A Systematic Review of the Literature. AB - The 2014 National Action Plan for Adverse Drug Event Prevention has recognized adverse drug events (ADEs) as a national priority in order to facilitate a nationwide reduction in patient harms from these events. Throughout this effort, it will be integral to identify populations that may be at particular risk in order to improve care for these patients. We have undertaken a systematic review to evaluate the evidence regarding racial or ethnic disparities in ADEs with particular emphasis on anticoagulants, diabetes agents, and opioids due to the clinical significance and preventability of ADEs associated with these medication classes. From an initial search yielding 3302 studies, we identified 40 eligible studies. Twenty-seven of these included studies demonstrated the presence of a racial or ethnic disparity. There was no consistent evidence for racial or ethnic disparities in the eight studies of ADEs in general. Asians were most frequently determined to be at higher risk of anticoagulant-related ADEs, and black patients were most frequently determined to be at higher risk for diabetes agents-related ADEs. Whites were most frequently identified as at increased risk for opioid related ADEs. However, few of these studies were specifically designed to evaluate racial or ethnic disparities, lacking a standardized approach to racial/ethnic categorization as well as control for potential confounders. We suggest the need for targeted interventions to reduce ADEs in populations that may be at increased risk, and we suggest strategies for future research. PMID- 26863558 TI - Improving Exercise Adherence and Physical Measures in English-Speaking Latina Women. AB - BACKGROUND: Epidemiological data have established that lack of physical activity increases risk factors for chronic diseases. Data also suggests that physical activity participation is lowest in minority women, particularly Latinas, and that the nature of the exercise and attitudes toward exercise may influence exercise adherence. The purpose of this study was to determine the effect of hypertrophy training (HT) or power training (PT) used concomitantly with evaluative conditioning (EC) or neutral conditioning (NC) on exercise adherence as well as in physical and psychosocial variables in Latina women. EC is a behavioral method using paired stimuli to develop and strengthen new associations in memory. METHODS: Two hundred thirty-one English-speaking Latina women (mean +/ SD, age 36.8 +/- 15.9 years) were randomly assigned to standard HT or high-speed circuit PT and then further stratified to receive EC or NC. RESULTS: One hundred forty-two Latina women completed pre- and posttesting. For HT, EC produced significantly greater exercise time across the training period than NC. HT and PT both significantly improved all physical, functional, and psychosocial variables, with exception of leg extension and usual gait speed (p < 0.05). CONCLUSION: EC can positively impact exercise adherence during HT in Latina women; while body composition, neuromuscular, and functional performances can be increased using HT and PT independent of psychological conditioning. PMID- 26863560 TI - A Primary Care-Based Early Childhood Nutrition Intervention: Evaluation of a Pilot Program Serving Low-Income Hispanic Women. AB - Nutrition in early childhood can significantly impact physical and mental health outcomes for children. However, research on broadly defined pre/postnatal nutrition interventions is sparse. The present study is a process and outcome evaluation of a primary care-based nutrition intervention targeting low-income Hispanic women. Pregnant women enrolled in the program were in their first trimester and received services through their 6-month well child check. The program provided vouchers for fruits and vegetables from the local farmers' market, nutrition classes, cooking classes, and lactation counseling. We conducted a prospective study of program participants (n = 32) and a comparable group of women for whom the program was not available (n = 29). Panel survey data measured maternal diet, exercise, stress, depression, social support, infant feeding practices, and demographics. Outcome measures obtained from medical records included pregnancy weight gain, infant weight at 6 and 12 months, and infant development at 9 months. Findings reveal that the program was not associated with infant weights. However, despite similar profiles at baseline, women in the intervention group were more likely than women in the comparison group to have significant improvements in diet, exercise, and depression (p <= .05). In addition, participants were more likely to breastfeed (p = .07) and their infants were more likely to pass the ages and stages developmental screen (p = .06) than women in the comparison group. The study was limited by a lack of random assignment and small samples. However, the breadth and size of the effects suggest pre/postnatal nutrition interventions integrated into primary care warrant additional investigation. PMID- 26863561 TI - Identity, Physical Space, and Stigma Among African American Men Living with HIV in Chicago and Seattle. AB - African American men have the highest rates of HIV in the USA, and research has shown that stigma, mistrust of health care, and other psychosocial factors interfere with optimal engagement in care with this population. In order to further understand reducing stigma and other psychosocial issues among African American men, we conducted qualitative interviews and focus groups with African American men in two metropolitan areas in the USA: Chicago and Seattle. We examined transcripts for relationships across variables of stigma, anonymity, self-identity, and space within the context of HIV. Our analysis pointed to similarities between experiences of stigma across the two cities and illustrated the relationships between space, isolation, and preferred anonymity related to living with HIV. The men in our study often preferred that their HIV-linked identities remain invisible and anonymous, associated with perceived and created isolation from physical community spaces. This article suggests that our health care and housing institutions may influence preferences for anonymity. We make recommendations in key areas to create safer spaces for African American men living with HIV and reduce feelings of stigma and isolation. PMID- 26863562 TI - Race, Ethnicity, and Self-Rated Health Among Immigrants in the United States. AB - OBJECTIVES: Previous work has not fully explored the role of race in the health of immigrants. We investigate race and ethnic differences in self-rated health (SRH) among immigrants, assess the degree to which socio-economic characteristics explain race and ethnic differences, and examine whether time in the USA affects racial and ethnic patterning of SRH among immigrants. METHODS: Data came from the 2012 National Health Interview Survey (N = 16, 288). Using logistic regression, we examine race and ethnic differences in SRH controlling for socio-economic differences and length of time in the country. RESULTS: Hispanic and non-Hispanic Black immigrants were the most socio-economically disadvantaged. Asian immigrants were socio-economically similar to non-Hispanic White immigrants. Contrary to U.S. racial patterning, Black immigrants had lower odds of poor SRH than did non Hispanic White immigrants when socio-demographic factors were controlled. When length of stay in the USA was included in the model, there were no racial or ethnic differences in SRH. However, living in the USA for 15 years and longer was associated with increased odds of poor SRH for all immigrants. CONCLUSIONS: Findings have implications for research on racial and ethnic disparities in health. Black-White disparities that have received much policy attention do not play out when we examine self-assessed health among immigrants. The reasons why non-Hispanic Black immigrants have similar self-rated health than non-Hispanic White immigrants even though they face greater socio-economic disadvantage warrant further attention. PMID- 26863563 TI - Long-Term Reciprocal Associations Between Depressive Symptoms and Number of Chronic Medical Conditions: Longitudinal Support for Black-White Health Paradox. AB - BACKGROUND: Previous research has identified a Black-White health paradox, which can be defined as less frequent depression despite a higher prevalence of chronic medical conditions among Blacks compared to Whites in the USA. Based on this paradox, we would expect weaker associations between chronic medical conditions and depression among Blacks than Whites. However, the literature on this topic is mostly cross-sectional and has provided findings that contradict the Black-White health paradox. The present longitudinal study extends prior research by assessing Black-White differences in reciprocal associations between number of chronic medical conditions and depressive symptoms over a 25-year period. METHODS: Data came from the Americans' Changing Lives Study that followed 1034 surviving Black and White respondents for 25 years from 1986 to 2011. Chronic medical conditions were measured based on a count of self-reported physician diagnoses including hypertension, diabetes, chronic lung disease, heart disease, stroke, cancer, and arthritis at baseline (1986) and follow-up (2011). Depressive symptoms were also measured at baseline and follow-up using a 10-item Center for Epidemiological Studies-Depression (CES-D) scale. Multi-group structural equation modeling was used to assess reciprocal associations between baseline and subsequent depressive symptoms and baseline and subsequent chronic medical conditions comparing Black and White respondents. RESULTS: Among White but not Black respondents, a higher number of chronic medical conditions at baseline predicted a greater increase in depressive symptoms over 25 years of follow-up. Among Whites but not Blacks, individuals with more depressive symptoms at baseline developed more chronic medical conditions over time. CONCLUSION: Findings documented Black-White differences in reciprocal associations between chronic medical conditions and depressive symptoms over time. Our study provides longitudinal evidence for the Black-White health paradox across mid and later life, as reciprocal associations between depression and chronic medical conditions were weaker for Blacks compared to Whites. PMID- 26863564 TI - Erratum to: Barriers and Facilitators to Recruitment to a Culturally Based Dietary Intervention Among Urban Hispanic Breast Cancer Survivors. PMID- 26863565 TI - Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin). AB - The genome is the target of some of the most effective chemotherapeutics, but most of these drugs lack DNA sequence specificity, which leads to dose-limiting toxicity and many adverse side effects. Targeting the genome with sequence specific small molecules may enable molecules with increased therapeutic index and fewer off-target effects. N-methylpyrrole/N-methylimidazole polyamides are molecules that can be rationally designed to target specific DNA sequences with exquisite precision. And unlike most natural transcription factors, polyamides can bind to methylated and chromatinized DNA without a loss in affinity. The sequence specificity of polyamides has been extensively studied in vitro with cognate site identification (CSI) and with traditional biochemical and biophysical approaches, but the study of polyamide binding to genomic targets in cells remains elusive. Here we report a method, the crosslinking of small molecules to isolate chromatin (COSMIC), that identifies polyamide binding sites across the genome. COSMIC is similar to chromatin immunoprecipitation (ChIP), but differs in two important ways: (1) a photocrosslinker is employed to enable selective, temporally-controlled capture of polyamide binding events, and (2) the biotin affinity handle is used to purify polyamide-DNA conjugates under semi denaturing conditions to decrease DNA that is non-covalently bound. COSMIC is a general strategy that can be used to reveal the genome-wide binding events of polyamides and other genome-targeting chemotherapeutic agents. PMID- 26863566 TI - The next generation of metastatic melanoma: uncovering the genetic variants for anti-BRAF therapy response. AB - Metastatic melanoma (MM) is a highly aggressive cancer with a median overall survival of 6-9 months, notwithstanding the numerous efforts in development of new therapeutic approaches. To this aim we tested the clinical applicability of the Ion Torrent Personal Genome Machine to simultaneously screen MM patients in order to individuate new or already known SNPs and mutations able to predict the duration of response to BRAF inhibitors. An Ampliseq Custom Panel, including 11 crucial full length genes involved in melanoma carcinogenesis and therapy response pathways, was created and used to analyze 25 MM patients. We reported BRAFV600 and NRASQ61 mutations in 68% and 24% of samples, respectively. Moreover, we more frequently identified the following alterations related to BRAF status: PIK3CAI391M (44%) and KITD737N (36%) mutations, CTLA4T17A (52%), MC1RV60L (32%) and MITFS473A (60%) polymorphisms. Considering the progression free survival (PFS), statistical analyses showed that BRAFV600 patients without any of these more frequent alterations had a higher median PFS. Protein structure changes seem to be due to these variants by in silico analysis. In conclusion, a Next Generation Sequencing approach with custom panel may provide new information to evaluate tumor-specific therapeutic susceptibility and individual prognosis to improve the care of MM patients. PMID- 26863568 TI - Characterization of long non-coding RNA-associated ceRNA network to reveal potential prognostic lncRNA biomarkers in human ovarian cancer. AB - Accumulating evidence has underscored the important roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in cancer initiation and progression. In this study, we used an integrative computational method to identify miRNA-mediated ceRNA crosstalk between lncRNAs and mRNAs, and constructed global and progression-related lncRNA-associated ceRNA networks (LCeNETs) in ovarian cancer (OvCa) based on "ceRNA hypothesis". The constructed LCeNETs exhibited small world, modular architecture and high functional specificity for OvCa. Known OvCa-related genes tended to be hubs and occurred preferentially in the functional modules. Ten lncRNA ceRNAs were identified as potential candidates associated with stage progression in OvCa using ceRNA network driven method. Finally, we developed a ten-lncRNA signature which classified patients into high- and low-risk subgroups with significantly different survival outcomes. Our study will provide novel insight for better understanding of ceRNA-mediated gene regulation in progression of OvCa and facilitate the identification of novel diagnostic and therapeutic lncRNA ceRNAs for OvCa. PMID- 26863567 TI - Aptamers: A promising chemical antibody for cancer therapy. AB - Aptamers, also known as chemical antibodies, are single-stranded nucleic acid oligonucleotides which bind to their targets with high specificity and affinity. They are typically selected by repetitive in vitro process termed systematic evolution of ligands by exponential enrichment (SELEX). Owing to their excellent properties compared to conventional antibodies, notably their smaller physical size and lower immunogenicity and toxicity, aptamers have recently emerged as a new class of agents to deliver therapeutic drugs to cancer cells by targeting specific cancer-associated hallmarks. Aptamers can also be structurally modified to make them more flexible in order to conjugate other agents such as nano materials and therapeutic RNA agents, thus extending their applications for cancer therapy. This review presents the current knowledge on the practical applications of aptamers in the treatment of a variety of cancers. PMID- 26863569 TI - ADAM10-mediated release of heregulin confers resistance to trastuzumab by activating HER3. AB - Receptor tyrosine kinases of the HER-family are involved in the development and progression of multiple epithelial tumors, and have consequently become widely used targets for new anti-cancer therapies. Trastuzumab, an antibody against HER2, has shown potent growth inhibitory effects on HER2 overexpressing tumors, including gastro-esophageal cancer, however, resistance to this therapy is inevitable. Unfortunately, a paucity of data on the cellular mechanisms of resistance to targeted therapeutic agents exists in esophageal adenocarcinoma. Using primary established HER2-overexpressing cultures and patient-derived xenograft models, we now reveal a novel resistance mechanism to trastuzumab in esophageal cancer: In response to trastuzumab, both HER3 and the metalloprotease ADAM10 are simultaneously upregulated. The proteolytic activity of the latter then releases the HER3 ligand heregulin from the cell surface to activate HER3 and confer resistance to trastuzumab by inducing compensatory growth factor receptor signaling. Blocking either HER3 or ADAM10 effectively reverts the acquired resistance to trastuzumab. Our data thus provide strategies to inhibit this signaling and circumvent resistance to trastuzumab. PMID- 26863570 TI - Long noncoding RNA OR3A4 promotes metastasis and tumorigenicity in gastric cancer. AB - The contribution of long noncoding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. We used microarray analysis to identify lncRNAs differentially expressed between normal gastric tissues and gastric cancer tissues and validated these differences in quantitative real-time (qRT)-PCR experiments. The expression levels of lncRNA olfactory receptor, family 3, subfamily A, member 4 (OR3A4) were significantly associated with lymphatic metastasis, the depth of cancer invasion, and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by overexpressing and silencing OR3A4 in gastric cancer cells. OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Global microarray analysis combined with RT-PCR, RNA immunoprecipitation, and RNA pull down analyses after OR3A4 transfection demonstrated that OR3A4 influenced biologic functions in gastric cancer cells via regulating the activation of PDLIM2, MACC1, NTN4, and GNB2L1. Our results reveal OR3A4 as an oncogenic lncRNA that promotes tumor progression, Therefore, lncRNAs might function as key regulatory hubs in gastric cancer progression. PMID- 26863571 TI - Neonatal bisphenol A exposure induces meiotic arrest and apoptosis of spermatogenic cells. AB - Bisphenol A (BPA) is a widely used industrial plasticizer, which is ubiquitously present in the environment and organisms. As an endocrine disruptor, BPA has caused significant concerns regarding its interference with reproductive function. However, little is known about the impact of BPA exposure on early testicular development. The aim of the present study was to investigate the influence of neonatal BPA exposure on the first wave of spermatogenesis. Newborn male mice were subcutaneously injected with BPA (0.01, 0.1 and 5 mg/kg body weight) daily from postnatal day (PND) 1 to 21. Histological analysis of testes at PND 22 revealed that BPA-treated testes contained mostly spermatogonia and spermatocytes with markedly less round spermatids, indicating signs of meiotic arrest. Terminal dUTP nick-end labeling (TUNEL) assay showed that BPA treatment significantly increased the number of apoptotic germ cells per tubule, which corroborated the observation of meiotic arrest. In addition, BPA caused abnormal proliferation of germ cells as revealed by Proliferating Cell Nuclear Antigen (PCNA) immunohistochemical staining. Mechanistically, BPA-treated testes displayed a complete lack of BOULE expression, which is a conserved key regulator for spermatogenesis. Moreover, BPA significantly increased the expression of estrogen receptor (ER) alpha and beta in the developing testis. The present study demonstrated that neonatal BPA exposure disrupted meiosis progression during the first wave of spermatogenesis, which may be, at least in part, due to inhibition of BOULE expression and/or up-regulation of ERalpha/beta expression in BPA exposed developing testis. PMID- 26863572 TI - Estrogen receptor beta as a prognostic factor in breast cancer patients: A systematic review and meta-analysis. AB - BACKGROUND: The prognostic role of estrogen receptor beta (ERbeta) in early-stage breast cancer is unclear. We performed a systematic review and meta-analysis to evaluate the prognostic value of ERbeta in early-stage breast cancer patients. METHOD: We searched Medline, Embase, and the Web of Science for studies published between 1990 and 2015 that assessed ERbeta status in breast cancer patients. A total of 25 studies comprising 9919 patients fitting our inclusion and exclusion criteria were included. The hazard ratios of ERbeta status were extracted for diseases free survival (DFS)/ ) and overall survival (OS). Random or fixed effects models were used when appropriate, and between-study heterogeneity was assessed. RESULTS: In the 20 studies that assessed ERbeta status using immunohistochemical (IHC) methods, we observed significantly improved DFS in patients positive for ERbeta-1 (HR=0.56, 95%CI 0.40-0.78, P=0.0007) and ERbeta-2 (HR=0.67, 95%CI 0.45-1.00, P=0.05). Improved OS was associated with a positive status for pan-ERbeta (HR=0.60, 95%CI 0.45-0.80, P=0.0004) and ERbeta-2 (HR=0.44, 95%CI 0.31-0.62, P<0.0001). In ERalpha-positive patients, ERbeta positivity was not associated with DFS (HR=0.77, 95%CI 0.46-1.27, P=0.31) or OS (HR=0.64, 95%CI 0.37-1.11, P=0.11). In contrast, ERbeta expression was significantly associated with increased DFS (HR=0.37, 95%CI 0.14-0.93, P=0.03) or OS (HR=0.44, 95%CI 0.30 0.65, P<0.0001) in ERalpha-negative patients. We did not observe an association between ERbeta mRNA levels and DFS and OS. CONCLUSION: In this study, we showed that IHC ERbeta status, rather than mRNA levels, is a prognostic factor that is associated with DFS and OS in breast cancer patients. The prognostic value of ERbeta may be higher in ERalpha-negative patients than in ERalpha-positive patients. PMID- 26863573 TI - Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology. AB - Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 MUL/min of whole blood), and high purity (avg. background of 28.8+/ 23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID- 26863574 TI - Administering and Detecting Protein Marks on Arthropods for Dispersal Research. AB - Monitoring arthropod movement is often required to better understand associated population dynamics, dispersal patterns, host plant preferences, and other ecological interactions. Arthropods are usually tracked in nature by tagging them with a unique mark and then re-collecting them over time and space to determine their dispersal capabilities. In addition to actual physical tags, such as colored dust or paint, various types of proteins have proven very effective for marking arthropods for ecological research. Proteins can be administered internally and/or externally. The proteins can then be detected on recaptured arthropods with a protein-specific enzyme-linked immunosorbent assay (ELISA). Here we describe protocols for externally and internally tagging arthropods with protein. Two simple experimental examples are demonstrated: (1) an internal protein mark introduced to an insect by providing a protein-enriched diet and (2) an external protein mark topically applied to an insect using a medical nebulizer. We then relate a step-by-step guide of the sandwich and indirect ELISA methods used to detect protein marks on the insects. In this demonstration, various aspects of the acquisition and detection of protein markers on arthropods for mark-release-recapture, mark-capture, and self-mark-capture types of research are discussed, along with the various ways that the immunomarking procedure has been adapted to suit a wide variety of research objectives. PMID- 26863575 TI - Prognostic Significance of Aquaporin 5 Expression in Non-small Cell Lung Cancer. AB - BACKGROUND: Aquaporins are water channel proteins that play a major role in the movement of water in various human tissues. Recently, it has been found that aquaporins have influence in the carcinogenesis of human malignancies. We analyzed the prognostic impact of aquaporin 5 (AQP5) in non-small lung cancer (NSCLC). METHODS: Seventy-six cases of NSCLC were studied, including 44 cases of adenocarcinoma (ADC) and 32 cases of squamous cell carcinoma (SQCC). Tissue microarray was constructed and immunohistochemical staining for AQP5 was performed. RESULTS: AQP5 was positive in 59.2% of the total enrolled NSCLCs (63.7% in ADC and 53.1% in SQCC). The difference in expression of AQP5 according to the histologic grade of the tumor was significant (p<.047), but not in a serial order. When ADC and SQCC were separately evaluated, no significant difference was observed according to the histologic grade of the tumor (p=.076 in ADC and p=.631 in SQCC). No difference was observed between AQP5 expression and other demographic data and tumor characteristics. Disease-free survival (DFS) was higher in AQP5 negative cases than positive cases in ADC (p=.047), but no significance was found in SQCC (p=.068). We were unable to find a significance between AQP5 overexpression and overall survival in either ADC (p=.210) or SQCC (p=.533). CONCLUSIONS: AQP5 expression is associated with DFS in ADC of the lung and tumor grade of NSCLC. The present study suggests that AQP5 can be a prognostic factor of NSCLC. PMID- 26863576 TI - Cardiac-protective effects and the possible mechanisms of alatamine during acute myocardial ischemia. AB - Alatamine is a constituent in the extract of a traditional herbal medicine Ramulus euonymi widely used for cardiac protection. However, its precise effects remain unclear. In the present study, we found that alatamine was able to reduce acute myocardial ischemia (AMI)-induced cardiac dysfunction in a rat model, as reflected by significantly restored electrocardiograms, M-mode echocardiograms, and left ventricular hemodynamics. Also, Nagar Olsen staining revealed that alatamine markedly reduced AMI-induced cardiac injury and cardiac myocyte apoptosis. TUNEL and caspase-3 activity assay showed that cardiac myocytes underwent significant apoptosis during AMI, and levels of LDH and CK-MB increased in the serum. However, such changes were significantly inhibited by pre administration of alatamine. Furthermore, such anti-apoptotic effects of alatamine was also confirmed in a cardiac myocyte model of isoproterenol (ISO) induced damage. Mechanistically, it was also found that alatamine improved the expression and activity of sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA), which were inhibited during AMI, promoting contractility and relaxation. Meanwhile, alatamine decreased Bax and increased Bcl-2 expressions both in vivo and in vitro, therefore inhibiting cardiac myocyte apoptosis and preventing cardiac dysfunction caused by AMI at the cellular level. The present study revealed the beneficial role of alatamine in cardiac protection and highlighted it as a potential therapeutic reagent for reduction of AMI-induced cardiac injury. PMID- 26863577 TI - Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. AB - OBJECTIVE: The purpose of this study was to determine whether gadolinium (Gd) is deposited in brain and bone tissues in patients receiving only non-Group 1 agents, either macrocyclic or linear protein interacting Gd-based contrast agents, with normal renal function. Group 1 agents are linear agents most associated with nephrogenic systemic fibrosis that the US Federal Drug Administration has defined as contraindicated in patients at risk for this disease. MATERIALS AND METHODS: This study was institutional review board approved and Health Insurance Portability and Accountability Act compliant for retrospective review of records and also had signed autopsy consent authorizing use of decedent's tissue in research studies. Tissue samples were collected from 9 decedents undergoing autopsy who had contrast-enhanced magnetic resonance imaging (MRI) with only single agent exposure to a non-Group 1 Gd-based contrast agent. Decedents with only noncontrast MRI or no MRI served as controls. Multiple brain areas, including globus pallidus and dentate nucleus, as well as bone and skin, were sampled and analyzed for Gd using inductively coupled plasma mass spectrometry. Gadolinium levels were compared between groups of decedents using the Mann-Whitney test and between brain and bone tissues of the same cases using the Wilcoxon signed-rank test. RESULTS: Of the 9 decedents, 5 received gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), 2 received gadobutrol (Gadovist; Bayer Healthcare, Whippany, NJ), and 1 each had gadobenate (MultiHance; Bracco Diagnostics) and gadoxetate (Eovist; Bayer Healthcare). Gadolinium was found with all agents in all brain areas sampled with highest levels in globus pallidus and dentate. Bone levels measured 23 times higher (median) than brain levels (P = 0.008 for bone vs globus pallidus) and showed a significant correlation (r = 0.81, P = 0.022). In controls, Gd levels in the brain were at or below limits of measurement and were significantly lower compared with study cases (P = 0.005 for globus pallidus). CONCLUSION: Gadolinium deposition in normal brain and bone tissue occurs with macrocyclic and linear protein interacting agents in patients with normal renal function. Deposition of Gd in cortical bone occurs at much higher levels compared with brain tissue and shows a notable correlation between the two. Thus, the bone may serve as a surrogate to estimate brain deposition if brain Gd were to become a useful clinical or research marker. PMID- 26863578 TI - Blind Compressed Sensing Enables 3-Dimensional Dynamic Free Breathing Magnetic Resonance Imaging of Lung Volumes and Diaphragm Motion. AB - OBJECTIVES: The objective of this study was to increase the spatial and temporal resolution of dynamic 3-dimensional (3D) magnetic resonance imaging (MRI) of lung volumes and diaphragm motion. To achieve this goal, we evaluate the utility of the proposed blind compressed sensing (BCS) algorithm to recover data from highly undersampled measurements. MATERIALS AND METHODS: We evaluated the performance of the BCS scheme to recover dynamic data sets from retrospectively and prospectively undersampled measurements. We also compared its performance against that of view-sharing, the nuclear norm minimization scheme, and the l1 Fourier sparsity regularization scheme. Quantitative experiments were performed on a healthy subject using a fully sampled 2D data set with uniform radial sampling, which was retrospectively undersampled with 16 radial spokes per frame to correspond to an undersampling factor of 8. The images obtained from the 4 reconstruction schemes were compared with the fully sampled data using mean square error and normalized high-frequency error metrics. The schemes were also compared using prospective 3D data acquired on a Siemens 3 T TIM TRIO MRI scanner on 8 healthy subjects during free breathing. Two expert cardiothoracic radiologists (R1 and R2) qualitatively evaluated the reconstructed 3D data sets using a 5-point scale (0-4) on the basis of spatial resolution, temporal resolution, and presence of aliasing artifacts. RESULTS: The BCS scheme gives better reconstructions (mean square error = 0.0232 and normalized high frequency = 0.133) than the other schemes in the 2D retrospective undersampling experiments, producing minimally distorted reconstructions up to an acceleration factor of 8 (16 radial spokes per frame). The prospective 3D experiments show that the BCS scheme provides visually improved reconstructions than the other schemes do. The BCS scheme provides improved qualitative scores over nuclear norm and l1 Fourier sparsity regularization schemes in the temporal blurring and spatial blurring categories. The qualitative scores for aliasing artifacts in the images reconstructed by nuclear norm scheme and BCS scheme are comparable.The comparisons of the tidal volume changes also show that the BCS scheme has less temporal blurring as compared with the nuclear norm minimization scheme and the l1 Fourier sparsity regularization scheme. The minute ventilation estimated by BCS for tidal breathing in supine position (4 L/min) and the measured supine inspiratory capacity (1.5 L) is in good correlation with the literature. The improved performance of BCS can be explained by its ability to efficiently adapt to the data, thus providing a richer representation of the signal. CONCLUSION: The feasibility of the BCS scheme was demonstrated for dynamic 3D free breathing MRI of lung volumes and diaphragm motion. A temporal resolution of ~500 milliseconds, spatial resolution of 2.7 * 2.7 * 10 mm, with whole lung coverage (16 slices) was achieved using the BCS scheme. PMID- 26863579 TI - Prediction Model For Extensive Ductal Carcinoma In Situ Around Early-Stage Invasive Breast Cancer. AB - OBJECTIVES: Ductal carcinoma in situ (DCIS) is a risk factor for incomplete resection of breast cancer. Especially, extensive DCIS (E-DCIS) or extensive intraductal component often results in positive resection margins. Detecting DCIS around breast cancer before treatment may therefore alter surgery. The purpose of this study was to develop a prediction model for E-DCIS around early-stage invasive breast cancer, using clinicohistopathological and dynamic contrast enhanced magnetic resonance imaging (MRI) features. MATERIALS AND METHODS: Dynamic contrast-enhanced MRI and local excision were performed in 322 patients with 326 ductal carcinomas. Tumors were segmented from dynamic contrast-enhanced MRI, followed by 3-dimensional extension of the margins with 10 mm. Amount of fibroglandular tissue (FGT) and enhancement features in these extended margins were automatically extracted from the MRI scans. Clinicohistopathological features were also obtained. Principal component analysis and multivariable logistic regression were used to develop a prediction model for E-DCIS. Discrimination and calibration were assessed, and bootstrapping was applied for internal validation. RESULTS: Extensive DCIS occurred in 48 (14.7%) of 326 tumors. Incomplete resection occurred in 56.3% of these E-DCIS-positive versus 9.0% of E-DCIS-negative tumors (P < 0.001). Five components with eigenvalue exceeding 1 were identified; 2 were significantly associated with E-DCIS. The first, positively associated, component expressed early and overall enhancement in the 10-mm tissue margin surrounding the MRI-visible tumor. The second, positively associated, component expressed human epidermal growth factor receptor 2 and amount of FGT around the MRI-visible tumor. The area under the curve value was 0.79 (0.76 after bootstrapping). CONCLUSIONS: Human epidermal growth factor receptor 2 status, early and overall enhancement in the 10-mm margin around the MRI-visible tumor, and amount of FGT in the 10 mm around the MRI-visible tumor were associated with E-DCIS. PMID- 26863580 TI - Comparison of Routine Brain Imaging at 3 T and 7 T. AB - OBJECTIVE: The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS: Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS: Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS: Ultra high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors. PMID- 26863581 TI - Ethanol-metabolizing activities and isozyme protein contents of alcohol and aldehyde dehydrogenases in human liver: phenotypic traits of the ADH1B*2 and ALDH2*2 variant gene alleles. AB - OBJECTIVE: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for the metabolism of ethanol. East Asian populations are unique in that they carry both a prevalent ADH1B*2 and a dominant negative ALDH2*2 allele. A systematic investigation of ethanol-metabolizing activities in normal livers correlated with the corresponding functional allelic variations and protein contents of the relevant isozymes in respective enzyme families has been lacking. MATERIALS AND METHODS: To obtain a reasonable sample size encompassing all possible genetic allelotypes of the ADH1B and ALDH2, 141 surgical liver specimens from adult Han Chinese were studied. Expression patterns and activities of ADH and ALDH were determined with stratification of the genetic phenotypes. Absolute protein contents as well as cellular localization of the activity and protein of ADH/ALDH isozymes were also investigated. RESULTS: The activities of ADH1B*1/*2 and ADH1B*2/*2 allelic phenotypes were 5-6-fold those of the ADH1B*1/*1, suggesting that ADH1B*2 allele-encoded subunits are dominant over expression of hepatic ADH activity. The activities of the ALDH2-active phenotype were 90% higher than those of the ALDH2-inactive phenotype. Sex and age did not significantly influence the hepatic ADH and ALDH activities with specified genetic phenotypes. The isozyme protein contents were as follows in decreasing order: ADH1, ADH2, ALDH1A1, ALDH2, and ADH3. Both ADH1, but not ADH2/3, and ALDH1A1/2 showed a preferential expression in perivenular hepatocytes. CONCLUSION: Functional correlations of ADH1B*2 and ALDH2*2 variant alleles in the liver provide a biochemical genetic basis suggesting their contribution toward variability in ethanol metabolism as well as susceptibility to alcoholism and alcohol-related diseases in East Asians. PMID- 26863582 TI - Patients suffering from rheumatic disease describing own experiences from participating in Basic Body Awareness Group Therapy: A qualitative pilot study. AB - BACKGROUND: Rheumatic diseases have physical and psychological impact on patients' movement and function. Basic Body Awareness Therapy focuses on promoting more functional movement quality in daily life. The purpose of this study was to describe patient experiences from participating in Basic Body Awareness Group Therapy for inpatients with rheumatic disease. METHODS: A phenomenological design included data collection in two focus group interviews with seven patients. Giorgi's four-step phenomenological method was used for data analysis. RESULTS: Four main themes emerged: (1) "Movement exploration-being guided in movement" described informants' exploration of bodily signals and movement habits; (2) "Movement awareness training in a relational perspective" informants described experiences from being in a group setting; (3) "Movement awareness-integration and insight" described informants' reflections on movement experiences; and (4) "Integrating and practicing new movement habits" informants described how they used their movement experiences in daily life. CONCLUSIONS: The study described perspectives in movement learning experienced by patients. The results support the view that contact with the body can help patients exploring and cultivating their own resources for a more functional movement quality. Descriptions of relational movement learning aspects can contribute to our understanding of physiotherapy group design. PMID- 26863583 TI - Good outcome of total hip replacement in patients with cerebral palsy: A comparison of 389 patients and 425,813 controls from the National Joint Registry for England and Wales. AB - BACKGROUND AND PURPOSE: People with cerebral palsy (CP) often have painful deformed hips, but they are seldom treated with hip replacement as the surgery is considered to be high risk. However, few data are available on the outcome of hip replacement in these patients. PATIENTS AND METHODS: We linked Hospital Episode Statistics (HES) records to the National Joint Registry for England and Wales to identify 389 patients with CP who had undergone hip replacement. Their treatment and outcomes were compared with those of 425,813 patients who did not have CP. Kaplan-Meier estimates were calculated to describe implant survivorship and the curves were compared using log-rank tests, with further stratification for age and implant type. Reasons for revision were quantified as patient-time incidence rates (PTIRs). Nationally collected patient-reported outcomes (PROMS) before and 6 months after operation were compared if available. Cumulative mortality (Kaplan Meier) was estimated at 90 days and at 1, 3, and 5 years. RESULTS: The cumulative probability of revision at 5 years post-surgery was 6.4% (95% CI: 3.8-11) in the CP cohort as opposed to 2.9% (CI 2.9-3%) in the non-CP cohort (p < 0.001). Patient-reported outcomes showed that CP patients had worse pain and function preoperatively, but had equivalent postoperative improvement. The median improvement in Oxford hip score at 6 months was 23 (IQR: 14-28) in CP and it was 21 (14-28) in non-CP patients. 91% of CP patients reported good or excellent satisfaction with their outcome. The cumulative probability of mortality for CP up to 7 years was similar to that in the controls after stratification for age and sex. INTERPRETATION: Hip replacement for cerebral palsy appears to be safe and effective, although implant revision rates are higher than those in patients without cerebral palsy. PMID- 26863584 TI - Lactoferrin Levels in Tears are Increased by the Topical Application of Diadenosine Tetraphosphate. AB - PURPOSE: This study was undertaken to determine the effect of the topical application of diadenosine tetraphosphate on lactoferrin levels in rabbit tears. METHODS: Diadenosine tetraphosphate was topically instilled in a single-dose, tear samples were collected by micropipette and lactoferrin was measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: The concentration of lactoferrin in rabbit tears was significantly increased 1 h after diadenosine tetraphosphate application, remaining elevated for 3 h more. This effect was blocked by P2 receptors antagonists. CONCLUSIONS: Topical application of diadenosine tetraphosphate stimulates the secretion of lactoferrin in rabbit tears through P2 receptor activation. PMID- 26863585 TI - Ankle Joint Angle and Lower Leg Musculotendinous Unit Responses to Cryotherapy. AB - Akehi, K, Long, BC, Warren, AJ, and Goad, CL. Ankle joint angle and lower leg musculotendinous unit responses to cryotherapy. J Strength Cond Res 30(9): 2482 2492, 2016-The use of cold application has been debated for its influence on joint range of motion (ROM) and stiffness. The purpose of this study was to determine whether a 30-minute ice bag application to the plantarflexor muscles or ankle influences passive ankle dorsiflexion ROM and lower leg musculotendinous stiffness (MTS). Thirty-five recreationally active college-aged individuals with no history of lower leg injury 6 months before data collection volunteered. On each testing day, we measured maximum passive ankle dorsiflexion ROM ( degrees ) and plantarflexor torque (N.m) on an isokinetic dynamometer to calculate the passive plantarflexor MTS (N.m per degree) at 4 joint angles before, during, and after a treatment. Surface electromyography amplitudes (MUV), and skin surface and ambient air temperature ( degrees C) were also measured. Subjects received an ice bag to the posterior lower leg, ankle joint, or nothing for 30 minutes in different days. Ice bag application to the lower leg and ankle did not influence passive ROM (F(12,396) = 0.67, p = 0.78). Passive torque increased after ice bag application to the lower leg (F(12,396) = 2.21, p = 0.011). Passive MTS at the initial joint angle increased after ice bag application to the lower leg (F(12,396) = 2.14, p = 0.014) but not at the other joint angles (p > 0.05). Surface electromyography amplitudes for gastrocnemius and soleus muscles increased after ice application to the lower leg (F(2,66) = 5.61, p = 0.006; F(12,396) = 3.60, p < 0.001). Ice bag application to the lower leg and ankle joint does not alter passive dorsiflexion ROM but increases passive ankle plantarflexor torque in addition to passive ankle plantarflexor MTS at the initial joint angle. PMID- 26863586 TI - Efficacy of a Four-Week Uphill Sprint Training Intervention in Field Hockey Players. AB - Jakeman, JR, McMullan, J, and Babraj, JA. Efficacy of a four-week uphill sprint training intervention in field hockey players. J Strength Cond Res 30(10): 2761 2766, 2016-Current evidence increasingly suggests that very short, supramaximal bouts of exercise can have significant health and performance benefits. Most research conducted in the area, however, uses laboratory-based protocols, which can lack ecological validity. The purpose of this study was to examine the effects of a high-intensity sprint training program on hockey-related performance measures. Fourteen semiprofessional hockey players either completed a 4-week high intensity training (HIT) intervention, consisting of a total of 6 sessions of HIT, which progressively increased in volume (n = 7), or followed their normal training program (Con; n = 7). Straight-line sprint speed, with and without a hockey stick and ball, and slalom sprint speed, with and without a hockey stick and ball, were used as performance indicators. Maximal sprint speed over 22.9 m was also assessed. On completion of the 4-week intervention, straight-line sprint speed improved significantly in the HIT group (~3%), with no changes in performance for the Con group. Slalom sprint speed, both with and without a hockey ball, was not significantly different after the training program in either group. Maximal sprint speed improved significantly (12.1%) in the HIT group, but there was no significant performance change in the Con group. The findings of this study indicate that a short period of HIT can significantly improve hockey related performance measures and could be beneficial to athletes and coaches in field settings. PMID- 26863587 TI - Exercise Training Alters the Bone Mineral Density of Hemodialysis Patients. AB - Marinho, SM, Moraes, C, Barbosa, JEdSM, Eduardo, JCC, Fouqe, D, Pelletier, S, and Mafra, D. Exercise training alters the bone mineral density of hemodialysis patients. J Strength Cond Res 30(10): 2918-2923, 2016-Patients with chronic kidney disease undergoing hemodialysis (HD) frequently present low bone mineral density (BMD), and exercise may be useful for treating bone loss. This study aimed to assess the effects of an intradialytic resistance exercise training program (RETP) on BMD in HD patients. Twenty-one patients were enrolled into 2 groups; 10 patients performed exercise (80.0% men; 46.9 +/- 12.1 years; 27.0 +/- 3.4 kg.m) and 11 patients were in the control group (54.5% men; 50.5 +/- 11.5 years; 24.1 +/- 8.7 kg.m). Dual-energy x-ray absorptiometry was used to measure the BMD, lean mass, and body fat before and after the supervised RETP (performed with elastic bands and ankle cuffs in both lower limbs 3 times a week for 24 weeks-72 sessions). In the exercise group, 30.0% of patients presented with osteopenia and 20.0% osteoporosis and in the control group, 45.5% osteopenia and 36.4% osteoporosis. Only in the exercise group, the osteoporosis percentage was reduced to 10.0% and the femoral neck BMD and T-score improved from 0.89 +/- 0.1 to 0.93 +/- 0.1 g.cm and from -1.3 +/- 0.8 to -1.0 +/- 0.8 g.cm (p <= 0.05), respectively, after the intervention. In contrast, these parameters were reduced in the control group. The results suggest that resistance exercise may be useful for improving the BMD in HD patients. In summary, 24 weeks of the supervised RETP played a role in improving the BMD of HD patients. PMID- 26863588 TI - "History had taken such a large piece out of my life" - Neuroscientist refugees from Hamburg during National Socialism. AB - Approximately 9,000 physicians were uprooted for so-called "racial" or "political" reasons by the Nazi regime and 6,000 fled Germany. These refugees are often seen as survivors who contributed to a "brain drain" from Germany. About 432 doctors (all specialties, private and academic) were dismissed from the major German city of Hamburg. Of these, 16 were Hamburg University faculty members dismissed from their government-supported positions for "racial" reasons, and, of these, five were neuroscientists. In a critical analysis, not comprehensively done previously, we will demonstrate that the brain drain did not equal a "brain gain." The annihilation of these five neuroscientists' careers under different but similar auspices, their shameful harassment and incarceration, financial expropriation by Nazi ransom techniques, forced migration, and roadblocks once reaching destination countries stalled and set back any hopes of research and quickly continuing once-promising careers. A major continuing challenge is finding ways to repair an open wound and obvious vacuum in the German neuroscience community created by the largely collective persecution of colleagues 80 years ago. PMID- 26863589 TI - Characterisation of the solid electrolyte interface during lithiation/delithiation of germanium in an ionic liquid. AB - In this paper, we present investigations of the interface of electrodeposited Ge during lithiation/delithiation in the ionic liquid 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide containing 0.5 M lithium bis(trifluoromethylsulfonyl)imide (LiTFSI/[Py1,4]TFSI). Cyclic voltammetry (CV) and infrared spectroscopy were used to study the electrochemistry and the changes in the electrolyte during the Li intercalation/deintercalation processes. From infrared spectroscopic analysis, it was found that the TFSI(-) anion decomposes during the lithiation process, resulting in the formation of a solid-liquid interface (SEI) layer. X-ray photoelectron spectroscopy was used to analyse the composition of the SEI layer and the changes in the electrodeposited germanium. Furthermore, atomic force microscopy (AFM) was used to evaluate the changes in the SEI layer which showed that the SEI layer was inhomogenous and changed during the lithiation/delithiation processes. PMID- 26863590 TI - High Throughput Danio Rerio Energy Expenditure Assay. AB - Zebrafish are an important model organism with inherent advantages that have the potential to make zebrafish a widely applied model for the study of energy homeostasis and obesity. The small size of zebrafish allows for assays on embryos to be conducted in a 96- or 384-well plate format, Morpholino and CRISPR based technologies promote ease of genetic manipulation, and drug treatment by bath application is viable. Moreover, zebrafish are ideal for forward genetic screens allowing for novel gene discovery. Given the relative novelty of zebrafish as a model for obesity, it is necessary to develop tools that fully exploit these benefits. Herein, we describe a method to measure energy expenditure in thousands of embryonic zebrafish simultaneously. We have developed a whole animal microplate platform in which we use 96-well plates to isolate individual fish and we assess cumulative NADH2 production using the commercially available cell culture viability reagent alamarBlue. In poikilotherms the relationship between NADH2 production and energy expenditure is tightly linked. This energy expenditure assay creates the potential to rapidly screen pharmacological or genetic manipulations that directly alter energy expenditure or alter the response to an applied drug (e.g. insulin sensitizers). PMID- 26863591 TI - Using Tomoauto: A Protocol for High-throughput Automated Cryo-electron Tomography. AB - Cryo-electron tomography (Cryo-ET) is a powerful three-dimensional (3-D) imaging technique for visualizing macromolecular complexes in their native context at a molecular level. The technique involves initially preserving the sample in its native state by rapidly freezing the specimen in vitreous ice, then collecting a series of micrographs from different angles at high magnification, and finally computationally reconstructing a 3-D density map. The frozen-hydrated specimen is extremely sensitive to the electron beam and so micrographs are collected at very low electron doses to limit the radiation damage. As a result, the raw cryo tomogram has a very low signal to noise ratio characterized by an intrinsically noisy image. To better visualize subjects of interest, conventional imaging analysis and sub-tomogram averaging in which sub-tomograms of the subject are extracted from the initial tomogram and aligned and averaged are utilized to improve both contrast and resolution. Large datasets of tilt-series are essential to understanding and resolving the complexes at different states, conditions, or mutations as well as obtaining a large enough collection of sub-tomograms for averaging and classification. Collecting and processing this data can be a major obstacle preventing further analysis. Here we describe a high-throughput cryo-ET protocol based on a computer-controlled 300kV cryo-electron microscope, a direct detection device (DDD) camera and a highly effective, semi-automated image processing pipeline software wrapper library tomoauto developed in-house. This protocol has been effectively utilized to visualize the intact type III secretion system (T3SS) in Shigella flexneri minicells. It can be applicable to any project suitable for cryo-ET. PMID- 26863592 TI - Nonlinear analysis of right atrial electrograms predicts termination of persistent atrial fibrillation within the left atrium by catheter ablation. AB - The termination of long-standing persistent atrial fibrillation (LS-pAF) can be achieved by stepwise catheter ablation (step-CA) within the left atrium (LA). Our study aims to applying complexity measures derived from nonlinear time series analysis in order to characterize LS-pAF in terms of organization and to identify patients in whom AF can be terminated from those in whom AF cannot be terminated by step-CA within the LA. A total of 33 consecutive patients (age 61 +/- 7 years, sustained AF duration 19 +/- 11 months) with LS-pAF underwent step-CA. The organization of right bipolar electrograms before and during the ablation procedure was assessed using the coarse-grained correlation dimension. LS-pAF was terminated into sinus rhythm or atrial tachycardia in 22 patients during step-CA within the LA (left terminated patients-LT). In 11 patients the ablation procedure failed to terminate AF within LA (not left terminated patients-NLT). The statistical analysis of the estimated coarse-grained correlation dimension revealed that a higher right atrial (RA) organization before step-CA was associated to AF termination within the LA. During the ablation procedure, the level of RA organization displayed distinctive evolution between LT and NLT patients with a significant organization increase before AF termination for the LT patients. PMID- 26863594 TI - Flower-like RuCu nanodendrites as catalysts for hydrogenation of p-nitrophenol with beta-cyclodextrin as promoters. AB - Flower-like ruthenium-copper (RuCu) nanodendrites were readily synthesized by RuCl3.xH2O and CuCl with oleylamine as the reducing agent, stabilizer and solvent. The nanodendrites contained various small particles and demonstrated efficient catalytic ability in the hydrogenation of p-nitrophenol as a model reaction. Notably, by adding beta-cyclodextrin, the reaction rate can be greatly enhanced. PMID- 26863595 TI - Transferability of different classical force fields for right and left handed alpha-helices constructed from enantiomeric amino acids. AB - Amino acids can form d and l enantiomers, of which the l enantiomer is abundant in nature. The naturally occurring l enantiomer has a greater preference for a right handed helical conformation, and the d enantiomer for a left handed helical conformation. The other conformations, that is, left handed helical conformations of the l enantiomers and right handed helical conformations of the d enantiomers, are not common. The energetic differences between left and right handed alpha helical peptide chains constructed from enantiomeric amino acids are investigated using quantum chemical calculations (using the M06/6-311g(d,p) level of theory). Further, the performances of commonly used biomolecular force fields (OPLS/AA, CHARMM27/CMAP and AMBER) to represent the different helical conformations (left and right handed) constructed from enantiomeric (D and L) amino acids are evaluated. 5- and 10-mer chains from d and l enantiomers of alanine, leucine, lysine, and glutamic acid, in right and left handed helical conformations, are considered in the study. Thus, in total, 32 alpha-helical polypeptides (4 amino acids * 4 conformations of 5-mer and 10-mer) are studied. Conclusions, with regards to the performance of the force fields, are derived keeping the quantum optimized geometry as the benchmark, and on the basis of phi and psi angle calculations, hydrogen bond analysis, and different long range helical order parameters. PMID- 26863596 TI - Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp. AB - BACKGROUND: Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. OBJECTIVE: To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. METHODS: Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. RESULTS: Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. CONCLUSION: Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy. PMID- 26863597 TI - Informed Consent, Use, and Storage of Digital Photography Among Mohs Surgeons in the United States. AB - BACKGROUND: Digital photography is pervasive in dermatology. Potential uses include monitoring untreated disease, disease progression and treatment response, evaluating medical and cosmetic treatment, determining surgical sites, educating trainees and colleagues, and publishing reports in scientific journals. However, the nature of use, storage, and informed consent practices for digital photography among dermatologic surgeons has not been investigated. OBJECTIVE: This study used a comprehensive survey to elucidate these elements to better define standard practice. MATERIALS AND METHODS: A survey was created on SurveyMonkey. An email with the survey link was sent to all members of the American College of Mohs Surgery listserv with 2 follow-up emails. RESULTS: One hundred fifty-eight Mohs surgeons responded to the survey. Respondents indicated a wide variety in the type of camera and storage modality used for patient photographs. There was a variety of opinions on how to conceal a patient's identity when using photographs for educational purposes, and what features of a photo make it identifiable. CONCLUSION: Dermatologic surgeons vary widely on practices of photo storage and opinions of identifiability. Dermatology as a specialty may consider generating a consensus statement on appropriate use and storage of digital photography in dermatology practice. PMID- 26863598 TI - Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial. AB - BACKGROUND: Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. OBJECTIVE: To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. MATERIALS AND METHODS: Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. RESULTS: Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). CONCLUSION: Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates. PMID- 26863599 TI - Defining the prognosis of chronic total occlusions during primary percutaneous coronary intervention. AB - BACKGROUND: The influence of coexisting collateral circulation between chronic total occlusion (CTO) and infarct-related artery (IRA) in patients with acute ST segment elevation myocardial infarction (STEMI) remains unclear. We aimed to investigate the impact of coexisting collateral circulation between CTO and IRA on early clinical outcomes in patients with acute STEMI. METHODS: A total of 1488 consecutive acute STEMI patients who underwent primary percutaneous coronary intervention were prospectively included in the study. After restoration of antegrade flow, the patients who had coexisting CTO and collateral supply from IRA were defined as the CTO-IRA-related (CIR) group (n=56). Patients with coexisting CTO but with no collateral supply from IRA were defined as the CTO-IRA unrelated (CIUR) group (n=104). Patients without coexisting CTO were defined as the non-CTO group (n=1328). RESULTS: Compared with the CIUR and non-CTO groups, the CIR group was significantly associated with higher Killip class of at least 2 (P<0.001) at presentation, a lower rate of postprocedural thrombolysis in myocardial infarction 2/3 flow (P<0.001), and myocardial perfusion grade 3 (P<0.001). Moreover, the CIR group had significantly higher in-hospital (P<0.001) and 30-day mortality (P<0.001). On multivariate regression analysis, the CIR group (odds ratio=15.96, 95% confidence interval=4.94-51.54; P<0.001) as well as age, post-PCI TIMI, Killip and NT-proBNP levels were independently associated with 30-day mortality. However, the CIUR group was not an independent predictor of early clinical outcomes. CONCLUSION: After restoration of antegrade flow, coexisting CTO supplied by IRA collaterals has unfavourable effects on procedural success, enzymatic infarct size and postprocedural haemodynamic conditions. These collaterals are also independent predictors of 30-day mortality in acute STEMI patients. PMID- 26863600 TI - Establishment of Genome-edited Human Pluripotent Stem Cell Lines: From Targeting to Isolation. AB - Genome-editing of human pluripotent stem cells (hPSCs) provides a genetically controlled and clinically relevant platform from which to understand human development and investigate the pathophysiology of disease. By employing site specific nucleases (SSNs) for genome editing, the rapid derivation of new hPSC lines harboring specific genetic alterations in an otherwise isogenic setting becomes possible. Zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 are the most commonly used SSNs. All of these nucleases function by introducing a double stranded DNA break at a specified site, thereby promoting precise gene editing at a genomic locus. SSN-meditated genome editing exploits two of the cell's endogenous DNA repair mechanisms, non-homologous end joining (NHEJ) and homology directed repair (HDR), to either introduce insertion/deletion mutations or alter the genome using a homologous repair template at the site of the double stranded break. Electroporation of hPSCs is an efficient means of transfecting SSNs and repair templates that incorporate transgenes such as fluorescent reporters and antibiotic resistance cassettes. After electroporation, it is possible to isolate only those hPSCs that incorporated the repair construct by selecting for antibiotic resistance. Mechanically separating hPSC colonies and confirming proper integration at the target site through genotyping allows for the isolation of correctly targeted and genetically homogeneous cell lines. The validity of this protocol is demonstrated here by using all three SSN platforms to incorporate EGFP and a puromycin resistance construct into the AAVS1 safe harbor locus in human pluripotent stem cells. PMID- 26863602 TI - Prevalence of colorectal adenomas in asymptomatic young adults: a window to early intervention? AB - OBJECTIVE: The prevalence of colorectal adenoma is increasing in the average-risk population. However, little research is available on colorectal adenoma in young adults under age 40. The aim of this study was to investigate the prevalence and risk factors of colorectal adenoma in 20- to 39-year-old adults. METHODS: We evaluated 4286 asymptomatic young adults aged 20 to 39 years who underwent first colonoscopy screening as part of an employer-provided health wellness programme at the Health Promotion Centre of Samsung Changwon Hospital, Korea from January 2011 to December 2013. Logistic regression modelling was used to identify risk factors for colorectal adenoma in asymptomatic young adults. RESULTS: The prevalence of colorectal adenoma and advanced adenoma was 11.6% (497/4286) and 0.9% (39/4286), respectively. By age group, the prevalence of colorectal adenoma was 5.4% (33/608) in participants aged 20 to 29 years and 12.6% (464/3678) in participants aged 30 to 39. Colorectal adenoma was found in 13.1% (403/3072) of men and 7.7% (94/1214) of women. Increased risk of colorectal adenoma was associated with age over 30 years (OR, 2.37; 95% CI, 1.64-3.42), current smoker status (OR, 1.48; 95% CI, 1.14-1.91), and alcohol consumption (OR, 1.29; 95% CI, 1.03-1.63). CONCLUSIONS: Our findings indicate that even if the prevalence of colorectal adenoma was low in young adults aged 20 to 39, being over 30, cigarette smoking, and alcohol consumption can affect young adults who have no other CRC risks. PMID- 26863601 TI - Influences of XDH genotype by gene-gene interactions with SUCLA2 for thiopurine induced leukopenia in Korean patients with Crohn's disease. AB - BACKGROUND: The impact of genetic variation in the thiopurine S-methyltransferase (TPMT) gene on thiopurine-induced leukopenia has been well demonstrated. Although xanthine dehydrogenase (XDH) is the second major contributor to azathioprine breakdown, polymorphisms in XDH have rarely been studied in IBD patients. We aim to access association between XDH variants and thiopurine-induced leukopenia by gene-gene interaction in a Crohn's disease (CD) population. STUDY: A total of 964 CD patients treated with thiopurines were recruited from a tertiary referral center. The association between four XDH variants (p.Gly172Arg, p.Asn1109Thr, p.Arg149Cys, and p.Thr910Lys) and thiopurine-induced leukopenia was analyzed in cases with early leukopenia (n = 66), late leukopenia (n = 264), and in controls without leukopenia (n = 632). Three non-synonymous SNPs, which we previously reported association with thiopurine-induced leukopenia, NUDT15 (p.Arg139Cys), SUCLA2 (p.Ser199Thr), and TPMT *3C were selected for epistasis analysis with the XDH variants. RESULTS: There was no significant association for two variants of XDH and thiopurine-induced leukopenia. In the epistasis analysis, only XDH (p.Asn1109Thr) * SUCLA2 (p.Ser199Thr) showed a statistically significant association with early leukopenia [odds ratio (OR) = 0.16; p = 0.03]. After genotype stratification, a positive association on the background of SUCLA2 wild type (199Ser) between the XDH (p.Asn1109Thr) and early leukopenia (OR = 4.39; p = 0.01) was detected. CONCLUSION: Genes associated with thiopurine-induced leukopenia can act in a complex interactive manner. Further studies are warranted to explore the mechanisms underlying the effects of the combination of XDH (p.Asn1109Thr) and SUCLA2 (199Ser) on thiopurine-induced leukopenia. PMID- 26863603 TI - Quasi Two-Dimensional Dye-Sensitized In2O3 Phototransistors for Ultrahigh Responsivity and Photosensitivity Photodetector Applications. AB - We report the development of dye-sensitized thin-film phototransistors consisting of an ultrathin layer (<10 nm) of indium oxide (In2O3) the surface of which is functionalized with a self-assembled monolayer of the light absorbing organic dye D102. The resulting transistors exhibit a preferential color photoresponse centered in the wavelength region of ~500 nm with a maximum photosensitivity of ~10(6) and a responsivity value of up to 2 * 10(3) A/W. The high photoresponse is attributed to internal signal gain and more precisely to charge carriers generated upon photoexcitation of the D102 dye which lead to the generation of free electrons in the semiconducting layer and to the high photoresponse measured. Due to the small amount of absorption of visible photons, the hybrid In2O3/D102 bilayer channel appears transparent with an average optical transmission of >92% in the wavelength range 400-700 nm. Importantly, the phototransistors are processed from solution-phase at temperatures below 200 degrees C hence making the technology compatible with inexpensive and temperature sensitive flexible substrate materials such as plastic. PMID- 26863605 TI - Further We Travel the Faster We Go. AB - The average travelling speed increases in a nontrivial manner with the travel distance. This leads to scaling-like relations on quite extended spatial scales, for all mobility modes taken together and also for a given mobility mode in part. We offer a wide range of experimental results, investigating and quantifying this universal effect and its measurable causes. The increasing travelling speed with the travel distance arises from the combined effects of: choosing the most appropriate travelling mode; the structure of the travel networks; the travel times lost in the main hubs, starting or target cities; and the speed limit of roads and vehicles. PMID- 26863604 TI - PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail. AB - In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an essential component for enriching PI(4)P and facilitating Smo activation. PI(4)P also binds mouse Smo (mSmo) and promotes its phosphorylation and ciliary accumulation. Finally, Hh treatment increases the interaction between Smo and PI(4)P but decreases the interaction between Ptc and PI(4)P, indicating that, in addition to promoting PI(4)P production, Hh regulates the pool of PI(4)P associated with Ptc and Smo. PMID- 26863607 TI - Respiratory Health - Exposure Measurements and Modeling in the Fragrance and Flavour Industry. AB - Although the flavor and fragrance industry is about 150 years old, the use of synthetic materials started more than 100 years ago, and the awareness of the respiratory hazard presented by some flavoring substances emerged only recently. In 2001, the US National Institute of Occupational Safety and Health (NIOSH) identified for the first time inhalation exposure to flavoring substances in the workplace as a possible occupational hazard. As a consequence, manufacturers must comply with a variety of workplace safety requirements, and management has to ensure the improvement of health and safety of the employees exposed to hazardous volatile organic compounds. In this sensitive context, MANE opened its facilities to an intensive measuring campaign with the objective to better estimate the real level of hazardous respiratory exposure of workers. In this study, exposure to 27 hazardous volatile substances were measured during several types of handling operations (weighing-mixing, packaging, reconditioning-transferring), 430 measurement results were generated, and were exploited to propose an improved model derived from the well-known ECETOC-TRA model. The quantification of volatile substances in the working atmosphere involved three main steps: adsorption of the chemicals on a solid support, thermal desorption, followed by analysis by gas chromatography-mass spectrometry. Our approach was to examine experimental measures done in various manufacturing workplaces and to define correction factors to reflect more accurately working conditions and habits. Four correction factors were adjusted in the ECETOC-TRA to integrate important exposure variation factors: exposure duration, percentage of the substance in the composition, presence of collective protective equipment and wearing of personal protective equipment. Verification of the validity of the model is based on the comparison of the values obtained after adaptation of the ECETOC-TRA model, according to various exposure scenarios, with the experimental values measured under real conditions. After examination of the predicted results, 98% of the values obtained with the proposed new model were above the experimental values measured in real conditions. This must be compared with the results of the classical ECETOC-TRA system, which generates only 37% of overestimated values. As the values generated by the new model intended to help decision-makers of the industry to implement adapted protective action and information, and considering the high variability of the working environments, it was of the utmost importance to us not to underestimate the exposure level. The proposed correction factors have been designed to achieve this goal. We wish to propose the present method as an improved monitoring tool to improve respiratory health and safety in the flavor and fragrance manufacturing facilities. PMID- 26863608 TI - Size and Sex-Dependent Shrinkage of Dutch Bees during One-and-a-Half Centuries of Land-Use Change. AB - Land-use change and global warming are important factors driving bee decline, but it is largely unknown whether these drivers have resulted in changes in the life history traits of bees. Recent studies have shown a stronger population decline of large- than small-bodied bee species, suggesting there may have been selective pressure on large, but not on small species to become smaller. Here we test this hypothesis by analyzing trends in bee body size of 18 Dutch species over a 147 year period using specimens from entomological collections. Large-bodied female bees shrank significantly faster than small-bodied female bees (6.5% and 0.5% respectively between 1900 and 2010). Changes in temperature during the flight period of bees did not influence the size-dependent shrinkage of female bees. Male bees did not shrink significantly over the same time period. Our results could imply that under conditions of declining habitat quantity and quality it is advantageous for individuals to be smaller. The size and sex-dependent responses of bees point towards an evolutionary response but genetic studies are required to confirm this. The declining body size of the large bee species that currently dominate flower visitation of both wild plants and insect-pollinated crops may have negative consequences for pollination service delivery. PMID- 26863606 TI - Toward Good Read-Across Practice (GRAP) guidance. AB - Grouping of substances and utilizing read-across of data within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity and, increasingly often, also on mechanistic (biological) similarity. While read-across can play a key role in complying with legislations such as the European REACH regulation, the lack of consensus regarding the extent and type of evidence necessary to support it often hampers its successful application and acceptance by regulatory authorities. Despite a potentially broad user community, expertise is still concentrated across a handful of organizations and individuals. In order to facilitate the effective use of read-across, this document aims to summarize the state-of-the-art, summarizes insights learned from reviewing ECHA published decisions as far as the relative successes/pitfalls surrounding read-across under REACH and compile the relevant activities and guidance documents. Special emphasis is given to the available existing tools and approaches, an analysis of ECHA's published final decisions associated with all levels of compliance checks and testing proposals, the consideration and expression of uncertainty, the use of biological support data and the impact of the ECHA Read-Across Assessment Framework (RAAF) published in 2015. PMID- 26863609 TI - Development and validation of a large, modular test meal with liquid and solid components for assessment of gastric motor and sensory function by non-invasive imaging. AB - BACKGROUND: Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study introduces the large 'Nottingham Test Meal' (NTM) for assessment of gastric motor and sensory function by non-invasive imaging. METHODS: NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and 12 solid agar-beads (0 kcal) with known breaking strength. Gastric fullness and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gastric emptying (GE) were measured in 24 healthy volunteers (HVs) by gastric scintigraphy (GS) and magnetic resonance imaging (MRI). The contribution of secretion to gastric volume was assessed. Parameters that describe GE were calculated from validated models. Inter-observer agreement and reproducibility were assessed. KEY RESULTS: NTM produced moderate fullness (VAS >=30) but no more than mild dyspeptic symptoms (VAS <30) in 24 HVs. Stable binding of meal components to labels in gastric conditions was confirmed. Distinct early and late phase GE were detected by both modalities. Liquid GE half-time was median 49 (95% CI: 36-62) min and 68 (57-71) min for GS and MRI, respectively. Differences between GS and MRI measurements were explained by the contribution of gastric secretion. Breaking strength for agar-beads was 0.8 N/m(2) such that median 25 (8 50) % intact agar-beads and 65 (47-74) % solid material remained at 120 min on MRI and GS, respectively. Good reproducibility for liquid GE parameters was present and GE was not altered by agar-beads. CONCLUSIONS & INFERENCES: The NTM provided an objective assessment of gastric motor and sensory function. The results were reproducible and liquid emptying was not affected by non-nutrient agar-beads. The method is potentially suitable for clinical practice. PMID- 26863611 TI - Survival after Radical Cystectomy for Bladder Cancer in Relation to Prior Non Muscle Invasive Disease in Quebec. AB - INTRODUCTION AND OBJECTIVES: The aim of this study was to assess if there is a difference in survival after radical cystectomy (RC) when examined in relation to prior non-muscle invasive bladder cancer (NMIBC) disease vs. invasive cancer de novo at time of diagnosis. METHODS: We conducted a retrospective study of all patients who underwent RC within Quebec health insurance medical services database during the years (2000-2009). Overall survival (OS) outcome was assessed with Kaplan-Meier curves and hazard ratios (HRs) adjusted for age and gender. RESULTS: A total of 2,671 subjects met the eligibility criteria. Among them, 19.8% had presumed prior NMIBC that further progressed to invasive disease. Median survival after RC for patients with presumed prior NMIBC was 4.3 years as compared to patients with presumed invasive disease de novo 3.7 years (p = 0.007, Wilcoxon test). Patients with presumed NMIBC at the time of diagnosis had a 16% decrease in the risk of mortality after RC, when compared to patients with presumed invasive BC de novo (HR 0.84, 95% CI 0.73-0.96 (p = 0.0166)). CONCLUSION: Our results suggest a slightly better prognosis, regarding OS after RC for patients with presumed NMIBC who progressed to invasive disease, when compared to patients with presumed invasive disease de novo at the time of diagnosis. PMID- 26863610 TI - All Roads Lead to Rome: Exploring Human Migration to the Eternal City through Biochemistry of Skeletons from Two Imperial-Era Cemeteries (1st-3rd c AD). AB - Migration within the Roman Empire occurred at multiple scales and was engaged in both voluntarily and involuntarily. Because of the lengthy tradition of classical studies, bioarchaeological analyses must be fully contextualized within the bounds of history, material culture, and epigraphy. In order to assess migration to Rome within an updated contextual framework, strontium isotope analysis was performed on 105 individuals from two cemeteries associated with Imperial Rome Casal Bertone and Castellaccio Europarco-and oxygen and carbon isotope analyses were performed on a subset of 55 individuals. Statistical analysis and comparisons with expected local ranges found several outliers who likely immigrated to Rome from elsewhere. Demographics of the immigrants show men and children migrated, and a comparison of carbon isotopes from teeth and bone samples suggests the immigrants may have significantly changed their diet. These data represent the first physical evidence of individual migrants to Imperial Rome. This case study demonstrates the importance of employing bioarchaeology to generate a deeper understanding of a complex ancient urban center. PMID- 26863612 TI - Posterior Corneal Elevation after Small Incision Lenticule Extraction for Moderate and High Myopia. AB - PURPOSE: To investigate the changes of posterior corneal elevation after small incision lenticule extraction (SMILE) for moderate and high myopia. METHODS: In this prospective study, fifty consecutive eyes of thirty patients (10 male, 20 female) who underwent SMILE for myopia and myopic astigmatism were included. Eyes were divided in two groups based on the preoperative spherical equivalent refraction: high myopia group (32 eyes, range -6.25D to -10.00D) and moderate myopia group (18 eyes, range -3.00D to -6.00D). Posterior corneal surfaces were measured by a Scheimpflug camera (Pentacam, Oculus Germany) preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Posterior central elevation (PCE) and posterior mean elevation (PME) at 17 predetermined points in the central-4mm area above the best-fit sphere were analyzed. RESULTS: No significant difference in the amount of posterior corneal elevation changes in the high myopia group was noted over time (P = 0.23 and P = 0.94 for PCE and PME, respectively). Similarly, the changes in the moderate myopia group before and after SMILE were not significant either (P = 0.34 and P = 0.40 for PCE and PME). A statistically significant correlation was found between the residual bed thickness and the shift of the PCE in the high myopia group at 12 months postoperatively (r = 0.53, P = 0.01). CONCLUSIONS: The results of this study suggest that the posterior corneal surface remain stable within one year after SMILE for both moderate and high myopia. The changes of PCE correlate to the residual bed thickness for high myopia. Long-term changes of posterior corneal surface need further investigation. PMID- 26863613 TI - CRYbetaA3/A1-Crystallin Knockout Develops Nuclear Cataract and Causes Impaired Lysosomal Cargo Clearance and Calpain Activation. AB - betaA3/A1-crystallin is an abundant structural protein of the lens that is very critical for lens function. Many different genetic mutations have been shown to associate with different types of cataracts in humans and in animal models. betaA3/A1-crystallin has four Greek key-motifs that organize into two crystallin domains. It shown to bind calcium with moderate affinity and has putative calcium binding site. Other than in the lens, betaA3/A1 is also expressed in retinal astrocytes, retinal pigment epithelial (RPE) cells, and retinal ganglion cells. The function of betaA3/A1-crystallin in the retinal cell types is well studied; however, a clear understanding of the function of this protein in the lens has not yet been established. In the current study, we generated the betaA3/A1 crystallin knockout (KO) mouse and explored the function of betaA3/A1-crystallin in lens development. Our results showed that betaA3-KO mice develop congenital nuclear cataract and exhibit persistent fetal vasculature condition. At the cellular level KO lenses show defective lysosomal clearance and accumulation of nuclei, mitochondria, and autophagic cargo in the outer cortical region of the lens. In addition, the calcium level and the expression and activity of calpain-3 were increased in KO lenses. Taken together, these results suggest the lack of betaA3-crystallin function in lenses, alters calcium homeostasis which in turn causes lysosomal defects and calpain activation. These defects are responsible for the development of nuclear cataract in KO lenses. PMID- 26863614 TI - Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells. AB - Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington's disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT dynein-p150Glued complex interactions. PMID- 26863615 TI - Sustained Enhancement of Lateral Inhibitory Circuit Maintains Cross Modal Cortical Reorganization. AB - Deprivation of one modality can lead to the improvement of other intact modalities. We have previously reported that visual deprivation drives AMPA receptors into synapses from layer4 to 2/3 in the barrel cortex and sharpens functional whisker-barrel map at layer2/3 2 days after the beginning of visual deprivation. Enhanced excitatory synaptic transmission at layer4-2/3 synapses is transient and returns to the base line level a week after the beginning of visual deprivation. Here we found that sharpened whisker-barrel function is maintained at least for a week in visually deprived animals. While increased AMPA receptor mediated synaptic transmission at layer4-2/3 synapses dropped to the base line a week after the beginning of visual deprivation, lateral inhibitory synaptic transmission onto the neighboring barrel was kept strengthened for a week of visually deprived animals. Thus, transient strengthening of excitatory synapses at layer4-2/3 in the barrel cortex could trigger the enhancement of inhibitory inputs to neighboring barrel, and sustained lateral inhibition can maintain the sharpening of whisker-barrel map in visually deprived animals. PMID- 26863616 TI - Lamellipodia and Membrane Blebs Drive Efficient Electrotactic Migration of Rat Walker Carcinosarcoma Cells WC 256. AB - The endogenous electric field (EF) may provide an important signal for directional cell migration during wound healing, embryonic development and cancer metastasis but the mechanism of cell electrotaxis is poorly understood. Additionally, there is no research addressing the question on the difference in electrotactic motility of cells representing various strategies of cell movement specifically blebbing vs. lamellipodial migration. In the current study we constructed a unique experimental model which allowed for the investigation of electrotactic movement of cells of the same origin but representing different modes of cell migration: weakly adherent, spontaneously blebbing (BC) and lamellipodia forming (LC) WC256 cells. We report that both BC and LC sublines show robust cathodal migration in a physiological EF (1-3 V/cm). The directionality of cell movement was completely reversible upon reversing the field polarity. However, the full reversal of cell direction after the change of EF polarity was much faster in the case of BC (10 minutes) than LC cells (30 minutes). We also investigated the distinct requirements for Rac, Cdc42 and Rho pathways and intracellular Ca2+ in electrotaxis of WC256 sublines forming different types of cell protrusions. It was found that Rac1 is required for directional movement of LC to a much greater extent than for BC, but Cdc42 and RhoA are more crucial for BC than for LC cells. The inhibition of ROCK did not affect electrotaxis of LC in contrast to BC cells. The results also showed that intracellular Ca2+ is essential only for the electrotactic reaction of BC cells. Moreover, inhibition of MLCK and myosin II did not affect the electrotaxis of LC in contrast to BC cells. In conclusion, our results revealed that both lamellipodia and membrane blebs can efficiently drive electrotactic migration of WC 256 carcinosarcoma cells, however directional migration is mediated by different signalling pathways. PMID- 26863617 TI - Population Based National Tuberculosis Prevalence Survey among Adults (>15 Years) in Pakistan, 2010-2011. AB - BACKGROUND: We aimed to determine the prevalence of pulmonary tuberculosis (TB) amongst the adult population in 2010-2011 in Pakistan. METHOD: A nationwide cross sectional survey with multistage cluster sampling was conducted among adults (>=15 years) in 95 clusters in 2010-2011. All consenting participants were screened for cough and by chest X-ray. Participants with presumptive TB submitted two sputum samples for smear microscopy, culture, and molecular testing if needed. The TB prevalence estimates were adjusted for missing data and the cluster design. RESULT: Of 131,329 eligible individuals, 105,913 (81%) participated in the survey, of whom 10,471 (9.9%) were eligible for sputum examination. We found 341 bacteriologically positive TB cases of whom 233 had sputum smear-positive TB. The adjusted prevalence estimates for smear and bacteriologically positive TB were 270/100,000 (95% confidence interval (CI) 217 323), and 398/100,000 (95% CI 333-463), respectively. Only 61% of the diagnosed TB cases screened positive on symptoms (cough >2wks), whereas the other TB cases were detected based on X-ray abnormalities. The TB prevalence increased with age and was 1.8 times higher among men than women. The prevalence-to-notification ratio of smear-positive TB was 3.1 (95% CI 2.5-3.7), was higher among men than women, and increased with age. CONCLUSION: Our data suggest that there is under detection and/or -notification of TB, especially among men and elderly. TB control should be strengthened specifically in these risk groups. X-ray examination should be combined with symptom screening to enhance case detection. PMID- 26863618 TI - High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson Learned from 7.0 Tesla. AB - BACKGROUND: Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details. METHODS: We screened 131 patients with HCM. 13 patients (9 males, 56 +/-31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 +/-31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis. RESULTS: All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol. CONCLUSIONS: CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE. PMID- 26863620 TI - Rigorous Training of Dogs Leads to High Accuracy in Human Scent Matching-To Sample Performance. AB - Human scent identification is based on a matching-to-sample task in which trained dogs are required to compare a scent sample collected from an object found at a crime scene to that of a suspect. Based on dogs' greater olfactory ability to detect and process odours, this method has been used in forensic investigations to identify the odour of a suspect at a crime scene. The excellent reliability and reproducibility of the method largely depend on rigor in dog training. The present study describes the various steps of training that lead to high sensitivity scores, with dogs matching samples with 90% efficiency when the complexity of the scents presented during the task in the sample is similar to that presented in the in lineups, and specificity reaching a ceiling, with no false alarms in human scent matching-to-sample tasks. This high level of accuracy ensures reliable results in judicial human scent identification tests. Also, our data should convince law enforcement authorities to use these results as official forensic evidence when dogs are trained appropriately. PMID- 26863619 TI - A Non-Synonymous Single Nucleotide Polymorphism in the HJURP Gene Associated with Susceptibility to Hepatocellular Carcinoma among Chinese. AB - OBJECTIVE: HJURP (Holliday Junction-Recognizing Protein) plays dual roles in DNA repair and in accurate chromosome segregation during mitosis. We examined whether the single nucleotide polymorphisms (SNPs) of HJURP were associated with the risk of occurrence of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers from well-known high-risk regions for HCC in China. METHODS: Twenty-four haplotype-tagging SNPs across HJURP were selected from HapMap data using the Haploview software. We genotyped these 24 SNPs using the using Sequenom's iPLEX assay in the Fusui population, consisting of 348 patients with HCC and 359 cancer-free controls, and further investigated the significantly associated SNP using the TaqMan assay in the Haimen population, consisting of 100 cases and 103 controls. The genetic associations with the risk of HCC were analyzed by logistic regression. RESULTS: We observed an increased occurrence of HCC consistently associated with A/C or C/C genotypes of the non-synonymous SNP rs3771333 compared with the A/A genotype in both the Fusui and Haimen populations, with a pooled odds ratio 1.82 (95% confidence interval, 1.33-2.49; P = 1.9 * 10-4). Case-only analysis further indicated that carriers of the at-risk C allele were younger than those carrying the A/A genotype (P = 0.0016). In addition, the expression levels of HJURP in C allele carriers were lower than that in A/A genotype carriers (P = 0.0078 and 0.0010, for mRNA and protein levels, respectively). CONCLUSION: Our findings suggest that rs3771333 in HJURP may play a role in mediating the susceptibility to HCC among Chinese. PMID- 26863621 TI - Effect of Concentrated Fibroblast-Conditioned Media on In Vitro Maintenance of Rat Primary Hepatocyte. AB - The effects of concentrated fibroblast-conditioned media were tested to determine whether hepatocyte function can be maintained without direct contact between hepatocytes and fibroblasts. Primary rat hepatocytes cultured with a concentrated conditioned media of NIH-3T3 J2 cell line (final concentration of 55 mg/ml) showed significantly improved survival and functions (albumin and urea) compared to those of control groups. They also showed higher expression levels of mRNA, albumin and tyrosine aminotransferase compared to hepatocyte monoculture. The results suggest that culture with concentrated fibroblast-conditioned media could be an easy method for in vitro maintenance of primary hepatocytes. They also could be contribute to understand and analyze co-culture condition of hepatocyte with stroma cells. PMID- 26863622 TI - The ER-Membrane Transport System Is Critical for Intercellular Trafficking of the NSm Movement Protein and Tomato Spotted Wilt Tospovirus. AB - Plant viruses move through plasmodesmata to infect new cells. The plant endoplasmic reticulum (ER) is interconnected among cells via the ER desmotubule in the plasmodesma across the cell wall, forming a continuous ER network throughout the entire plant. This ER continuity is unique to plants and has been postulated to serve as a platform for the intercellular trafficking of macromolecules. In the present study, the contribution of the plant ER membrane transport system to the intercellular trafficking of the NSm movement protein and Tomato spotted wilt tospovirus (TSWV) is investigated. We showed that TSWV NSm is physically associated with the ER membrane in Nicotiana benthamiana plants. An NSm-GFP fusion protein transiently expressed in single leaf cells was trafficked into neighboring cells. Mutations in NSm that impaired its association with the ER or caused its mis-localization to other subcellular sites inhibited cell-to cell trafficking. Pharmacological disruption of the ER network severely inhibited NSm-GFP trafficking but not GFP diffusion. In the Arabidopsis thaliana mutant rhd3 with an impaired ER network, NSm-GFP trafficking was significantly reduced, whereas GFP diffusion was not affected. We also showed that the ER-to-Golgi secretion pathway and the cytoskeleton transport systems were not involved in the intercellular trafficking of TSWV NSm. Importantly, TSWV cell-to-cell spread was delayed in the ER-defective rhd3 mutant, and this reduced viral infection was not due to reduced replication. On the basis of robust biochemical, cellular and genetic analysis, we established that the ER membrane transport system serves as an important direct route for intercellular trafficking of NSm and TSWV. PMID- 26863623 TI - Climate and the Timing of Imported Cases as Determinants of the Dengue Outbreak in Guangzhou, 2014: Evidence from a Mathematical Model. AB - As the world's fastest spreading vector-borne disease, dengue was estimated to infect more than 390 million people in 2010, a 30-fold increase in the past half century. Although considered to be a non-endemic country, mainland China had 55,114 reported dengue cases from 2005 to 2014, of which 47,056 occurred in 2014. Furthermore, 94% of the indigenous cases in this time period were reported in Guangdong Province, 83% of which were in Guangzhou City. In order to determine the possible determinants of the unprecedented outbreak in 2014, a population based deterministic model was developed to describe dengue transmission dynamics in Guangzhou. Regional sensitivity analysis (RSA) was adopted to calibrate the model and entomological surveillance data was used to validate the mosquito submodel. Different scenarios were created to investigate the roles of the timing of an imported case, climate, vertical transmission from mosquitoes to their offspring, and intervention. The results suggested that an early imported case was the most important factor in determining the 2014 outbreak characteristics. Precipitation and temperature can also change the transmission dynamics. Extraordinary high precipitation in May and August, 2014 appears to have increased vector abundance. Considering the relatively small number of cases in 2013, the effect of vertical transmission was less important. The earlier and more frequent intervention in 2014 also appeared to be effective. If the intervention in 2014 was the same as that in 2013, the outbreak size may have been over an order of magnitude higher than the observed number of new cases in 2014.The early date of the first imported and locally transmitted case was largely responsible for the outbreak in 2014, but it was influenced by intervention, climate and vertical transmission. Early detection and response to imported cases in the spring and early summer is crucial to avoid large outbreaks in the future. PMID- 26863624 TI - Adsorption of Amorphous Silica Nanoparticles onto Hydroxyapatite Surfaces Differentially Alters Surfaces Properties and Adhesion of Human Osteoblast Cells. AB - Silicon (Si) is suggested to be an important/essential nutrient for bone and connective tissue health. Silicon-substituted hydroxyapatite (Si-HA) has silicate ions incorporated into its lattice structure and was developed to improve attachment to bone and increase new bone formation. Here we investigated the direct adsorption of silicate species onto an HA coated surface as a cost effective method of incorporating silicon on to HA surfaces for improved implant osseointegration, and determined changes in surface characteristics and osteoblast cell adhesion. Plasma-sprayed HA-coated stainless steel discs were incubated in silica dispersions of different concentrations (0-42 mM Si), at neutral pH for 12 h. Adsorbed Si was confirmed by XPS analysis and quantified by ICP-OES analysis following release from the HA surface. Changes in surface characteristics were determined by AFM and measurement of surface wettability. Osteoblast cell adhesion was determined by vinculin plaque staining. Maximum Si adsorption to the HA coated disc occurred after incubation in the 6 mM silica dispersion and decreased progressively with higher silica concentrations, while no adsorption was observed with dispersions below 6 mM Si. Comparison of the Si dispersions that produced the highest and lowest Si adsorption to the HA surface, by TEM-based analysis, revealed an abundance of small amorphous nanosilica species (NSP) of ~1.5 nm in diameter in the 6 mM Si dispersion, with much fewer and larger NSP in the 42 mM Si dispersions. 29Si-NMR confirmed that the NSPs in the 6 mM silica dispersion were polymeric and similar in composition to the larger NSPs in the 42 mM Si dispersion, suggesting that the latter were aggregates of the former. Amorphous NSP adsorbed from the 6 mM dispersion on to a HA-coated disc surface increased the surface's water contact angle by 53 degrees , whereas that adsorbed from the 42 mM dispersion decreased the contact angle by 18 degrees , indicating increased and decreased hydrophobicity, respectively. AFM showed an increase in surface roughness of the 6 mM Si treated surface, which correlated well with an increase in number of vinculin plaques. These findings suggest that NSP of the right size (relative to charge) adsorb readily to the HA surface, changing the surface characteristics and, thus, improving osteoblast cell adhesion. This treatment provides a simple way to modify plasma-coated HA surfaces that may enable improved osseointegration of bone implants. PMID- 26863625 TI - Retrospective Attention Gates Discrete Conscious Access to Past Sensory Stimuli. AB - Cueing attention after the disappearance of visual stimuli biases which items will be remembered best. This observation has historically been attributed to the influence of attention on memory as opposed to subjective visual experience. We recently challenged this view by showing that cueing attention after the stimulus can improve the perception of a single Gabor patch at threshold levels of contrast. Here, we test whether this retro-perception actually increases the frequency of consciously perceiving the stimulus, or simply allows for a more precise recall of its features. We used retro-cues in an orientation-matching task and performed mixture-model analysis to independently estimate the proportion of guesses and the precision of non-guess responses. We find that the improvements in performance conferred by retrospective attention are overwhelmingly determined by a reduction in the proportion of guesses, providing strong evidence that attracting attention to the target's location after its disappearance increases the likelihood of perceiving it consciously. PMID- 26863626 TI - Reliability and Validity of an Interviewer-Administered Adaptation of the Youth Self-Report for Mental Health Screening of Vulnerable Young People in Ethiopia. AB - OBJECTIVE: Evaluate the reliability and validity of the Youth Self-Report (YSR) as a screening tool for mental health problems among young people vulnerable to HIV in Ethiopia. DESIGN: A cross-sectional assessment of young people currently receiving social services. METHODS: Young people age 15-18 participated in a study where a translated and adapted version of the YSR was administered by trained nurses, followed by an assessment by Ethiopian psychiatrists. Internal reliability of YSR syndrome scales were assessed using Chronbach's alpha. Test retest reliability was assessed through repeating the YSR one month later. To assess validity, analysis of the sensitivity and specificity of the YSR compared to the psychiatrist assessment was conducted. RESULTS: Across the eight syndrome scales, the YSR best measured the diagnosis of anxiety/depression and social problems among young women, and attention problems among young men. Among individual YSR syndrome scales, internal reliability ranged from unacceptable (Chronback's alpha = 0.11, rule-breaking behavior among young women) to good (alpha>=0.71, anxiety/depression among young women). Anxiety/depression scores of >=8.5 among young women also had good sensitivity (0.833) and specificity (0.754) to predict a true diagnosis. The YSR syndrome scales for social problems among young women and attention problems among young men also had fair consistency and validity measurements. Most YSR scores had significant positive correlations between baseline and post-one month administration. Measures of reliability and validity for most other YSR syndrome scales were fair to poor. CONCLUSIONS: The adapted, personally administered, Amharic version of the YSR has sufficient reliability and validity in identifying young vulnerable women with anxiety/depression and/or social problems, and young men with attention problems; which were the most common mental health disorders observed by psychiatrists among the migrant populations in this study. Further assessment of the applicability of the YSR among vulnerable young people for less common disorders in Ethiopia is needed. PMID- 26863627 TI - Dysphagia in Acute Stroke: Incidence, Burden and Impact on Clinical Outcome. AB - BACKGROUND: Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke. METHODS: We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia. RESULTS: Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4+/-2.8 vs. 2.7+/ 2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality. CONCLUSION: Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization. PMID- 26863629 TI - miR-217 and CAGE form feedback loop and regulates the response to anti-cancer drugs through EGFR and HER2. AB - MicroRNA array analysis revealed that miR-217 expression was decreased in anti cancer drug-resistant Malme3MR cancer cells. CAGE, a cancer/testis antigen, was predicted as a target of miR-217. Luciferase activity and ChIP assays revealed a negative feedback relationship between CAGE and miR-217. miR-217 and CAGE oppositely regulated the response to anti-cancer drugs such as taxol, gefitinib and trastuzumab, an inhibitor of HER2. miR-217 negatively regulated the tumorigenic, metastatic, angiogenic, migration and invasion potential of cancer cells. The xenograft of Malme3MR cells showed an increased expression of pEGFRY845. CAGE and miR-217 inhibitor regulated the expression of pEGFRY845. CAGE showed interactions with EGFR and HER2 and regulated the in vivo sensitivity to trastuzumab. The down-regulation of EGFR or HER2 enhanced the sensitivity to anti cancer drugs. CAGE showed direct regulation of HER2 and was necessary for the interaction between EGFR and HER2 in Malme3MR cells. miR-217 inhibitor induced interactions of CAGE with EGFR and HER2 in Malme3M cells. The inhibition of EGFR by CAGE-binding GTGKT peptide enhanced the sensitivity to gefitinib and trastuzumab and prevented interactions of EGFR with CAGE and HER2. Our results show that miR-217-CAGE feedback loop serves as a target for overcoming resistance to various anti-cancer drugs, including EGFR and HER2 inhibitors. PMID- 26863628 TI - Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma. AB - We postulated that multicentric glioblastoma (GBM) represents more invasiveness form than solitary GBM and has their own genomic characteristics. From May 2004 to June 2010 we retrospectively identified 51 treatment-naive GBM patients with available clinical information from the Samsung Medical Center data registry. Multicentricity of the tumor was defined as the presence of multiple foci on the T1 contrast enhancement of MR images or having high signal for multiple lesions without contiguity of each other on the FLAIR image. Kaplan-Meier survival analysis demonstrated that multicentric GBM had worse prognosis than solitary GBM (median, 16.03 vs. 20.57 months, p < 0.05). Copy number variation (CNV) analysis revealed there was an increase in 11 regions, and a decrease in 17 regions, in the multicentric GBM. Gene expression profiling identified 738 genes to be increased and 623 genes to be decreased in the multicentric radiophenotype (p < 0.001). Integration of the CNV and expression datasets identified twelve representative genes: CPM, LANCL2, LAMP1, GAS6, DCUN1D2, CDK4, AGAP2, TSPAN33, PDLIM1, CLDN12, and GTPBP10 having high correlation across CNV, gene expression and patient outcome. Network and enrichment analyses showed that the multicentric tumor had elevated fibrotic signaling pathways compared with a more proliferative and mitogenic signal in the solitary tumors. Noninvasive radiological imaging together with integrative radiogenomic analysis can provide an important tool in helping to advance personalized therapy for the more clinically aggressive subset of GBM. PMID- 26863630 TI - EIF2S3Y suppresses the pluripotency state and promotes the proliferation of mouse embryonic stem cells. AB - Eukaryotic translation initiation factor 2, subunit 3, and structural gene Y linked (EIF2S3Y) is essential for spermatogenesis in mouse models. However, its effect on embryonic stem (ES) cells remains unknown. In our observation, differentiated ES cells showed higher levels of EIF2S3Y. To further elucidate its role in ES cells, we utilized ES-derived EIF2S3Y-overexpressing cells and found that EIF2S3Y down-regulated the pluripotency state of ES cells, which might be explained by decreased histone methylation levels because of reduced levels of ten-eleven translocation 1 (TET1). Moreover, EIF2S3Y-overexpressing cells showed an enhanced proliferation rate, which might be due to increased Cyclin A and Cyclin E levels. This study highlighted novel roles of EIF2S3Y in the pluripotency maintenance and proliferation control of ES cells, which would provide an efficient model to study germ cell generation as well as cancer development using ES cells, thus providing valuable target for clinical applications of ES cells. PMID- 26863631 TI - Efficacy of continued cetuximab for unresectable metastatic colorectal cancer after disease progression during first-line cetuximab-based chemotherapy: a retrospective cohort study. AB - This study assessed second-line continued use of cetuximab for treatment of unresectable metastatic colorectal cancer (mCRC) after disease progression during first-line cetuximab-based therapy. Consecutive patients with wild-type KRAS exon 2 and unresectable mCRC were retrospectively enrolled after disease progression during first-line cetuximab-based chemotherapy. Second-line continued cetuximab plus changed chemotherapy (cetuximab continuation group, n = 102) was compared with changed chemotherapy only (chemotherapy only group, n = 96) with respect to treatment efficacy and safety endpoints. NRAS and other KRAS genotypes were also detected as a post hoc analysis. The cetuximab continuation group showed better progression-free survival (median, 6.3 vs. 4.5 months, P = 0.004), overall survival (median, 17.3 vs. 14.0 months, P < 0.001) and disease control rate (70.6% vs. 53.1%, P = 0.011), and a potentially better overall response rate (18.6% vs. 9.4%, P = 0.062) than the chemotherapy only group. These benefits were seen mainly in patients with all RAS wild-type and exhibiting first-line early tumor shrinkage (ETS). For patients with other RAS mutations or who did not achieve first-line ETS, there was no difference between the two groups. These findings suggest that for patients with all RAS wild-type and unresectable mCRC who had disease progression during first-line cetuximab-based treatment, second line continued cetuximab is effective. Moreover, ETS during first-line cetuximab based treatment may be predictive of the efficacy of second-line continued cetuximab. PMID- 26863632 TI - Oncogenic potential of histone-variant H2A.Z.1 and its regulatory role in cell cycle and epithelial-mesenchymal transition in liver cancer. AB - H2A.Z is a highly conserved H2A variant, and two distinct H2A.Z isoforms, H2A.Z.1 and H2A.Z.2, have been identified as products of two non-allelic genes, H2AFZ and H2AFV. H2A.Z has been reported to be overexpressed in breast, prostate and bladder cancers, but most studies did not clearly distinguish between isoforms. One recent study reported a unique role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. Here we first report that H2A.Z.1 plays a pivotal role in the liver tumorigenesis by selectively regulating key molecules in cell cycle and epithelial-mesenchymal transition (EMT). H2AFZ expression was significantly overexpressed in a large cohort of hepatocellular carcinoma (HCC) patients, and high expression of H2AFZ was significantly associated with their poor prognosis. H2A.Z.1 overexpression was demonstrated in a subset of human HCC and cell lines. H2A.Z.1 knockdown suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins and caused apoptotic cell death of HCC cells. We also observed that H2A.Z.1 knockdown reduced the metastatic potential of HCC cells by selectively modulating epithelial-mesenchymal transition regulatory proteins such as E-cadherin and fibronectin. In addition, H2A.Z.1 knockdown reduced the in vivo tumor growth rate in a mouse xenograft model. In conclusion, our findings suggest the oncogenic potential of H2A.Z.1 in liver tumorigenesis and that it plays established role in accelerating cell cycle transition and EMT during hepatocarcinogenesis. This makes H2A.Z.1 a promising target in liver cancer therapy. PMID- 26863634 TI - Large-scale profiling of signalling pathways reveals an asthma specific signature in bronchial smooth muscle cells. AB - BACKGROUND: Bronchial smooth muscle (BSM) cells from asthmatic patients maintain in vitro a distinct hyper-reactive ("primed") phenotype, characterized by increased release of pro-inflammatory factors and mediators, as well as hyperplasia and/or hypertrophy. This "primed" phenotype helps to understand pathogenesis of asthma, as changes in BSM function are essential for manifestation of allergic and inflammatory responses and airway wall remodelling. OBJECTIVE: To identify signalling pathways in cultured primary BSMs of asthma patients and non-asthmatic subjects by genome wide profiling of differentially expressed mRNAs and activated intracellular signalling pathways (ISPs). METHODS: Transcriptome profiling by cap-analysis-of-gene-expression (CAGE), which permits selection of preferentially capped mRNAs most likely to be translated into proteins, was performed in human BSM cells from asthmatic (n=8) and non-asthmatic (n=6) subjects and OncoFinder tool were then exploited for identification of ISP deregulations. RESULTS: CAGE revealed >600 RNAs differentially expressed in asthma vs control cells (p<=0.005), with asthma samples showing a high degree of similarity among them. Comprehensive ISP activation analysis revealed that among 269 pathways analysed, 145 (p<0.05) or 103 (p<0.01) are differentially active in asthma, with profiles that clearly characterize BSM cells of asthmatic individuals. Notably, we identified 7 clusters of coherently acting pathways functionally related to the disease, with ISPs down-regulated in asthma mostly targeting cell death-promoting pathways and up-regulated ones affecting cell growth and proliferation, inflammatory response, control of smooth muscle contraction and hypoxia-related signalization. CONCLUSIONS: These first-time results can now be exploited toward development of novel therapeutic strategies targeting ISP signatures linked to asthma pathophysiology. PMID- 26863633 TI - Examining plasma microRNA markers for colorectal cancer at different stages. AB - Circulating microRNAs (miRNAs) have emerged as promising biomarkers; however, few miRNAs have been reproducible and can be used in clinical practice. In this study, we screened the levels of 754 miRNAs using TaqMan array in 50 individual plasma samples from 10 demographically matched healthy controls and 40 colorectal cancer (CRC) patients (10 each of stage I-IV) and identified 22 miRNAs associated with the presence of and stages of CRC. Then we performed the validation for 11 miRNAs in an independent cohort including 187 CRC cases and 47 healthy controls. Comprehensive analyses showed that plasma miR-96 distinguished stage I-IV CRC from healthy controls with an area under curve (AUC) of 0.740; miR-203 separated stage III-IV CRC patients from stage I-II with an AUC of 0.757; and miR-141 differentiated stage IV CRC from stage I-III patients with an AUC of 0.851. Survival analyses showed that plasma miR-96 and miR-200b were independent prognostic factors for overall survival. Thus, we propose four miRNAs (miR-96, miR-203, miR-141 and miR-200b) as clinically validated circulating biomarkers for CRC prognosis that warrant further evaluation for clinical utility. PMID- 26863636 TI - The impact of ranitidine on monocyte responses in the context of solid tumors. AB - Monocytes and myeloid derived suppressor cells (MDSC) have been implicated on the regulation of tumor growth. Histamine is also important for regulating MDSC responses. Oral administration of the H2 receptor antagonist ranitidine can inhibit breast tumor growth and metastasis. In the current study, we examined the impact of oral ranitidine treatment, at a clinically relevant dose, on multiple murine tumor models. The impact of ranitidine on monocyte responses and the role of CCR2 in ranitidine-induced tumor growth inhibition were also investigated. Oral ranitidine treatment did not reduce tumor growth in the B16-F10 melanoma, LLC1 lung cancer and EL4 thymoma models. However, it consistently reduced E0771 primary tumor growth and metastasis in the 4T1 model. Ranitidine had no impact on E0771 tumor growth in mice deficient in CCR2, where monocyte recruitment to tumors was limited. Analysis of splenic monocytes also revealed an elevated ratio of H2 versus H1 expression from tumor-bearing compared with naive mice. More detailed examination of the role of ranitidine on monocyte development demonstrated a decrease in monocyte progenitor cells following ranitidine treatment. Taken together, these results reveal that H2 signaling may be a novel target to alter the monocyte population in breast tumor models, and that targeting H2 on monocytes via oral ranitidine treatment impacts effective tumor immunity. Ranitidine is widely used for control of gastrointestinal disorders. The potential role of ranitidine as an adjunct to immunotherapies for breast cancer and the potential impact of H2 antagonists on breast cancer outcomes should be considered. PMID- 26863635 TI - Dynamics of cytotoxic T cell subsets during immunotherapy predicts outcome in acute myeloid leukemia. AB - Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were drawn during cycles of immunotherapy and analyzed for CD8+ (cytotoxic) T cell phenotypes in blood. During the first cycle of therapy, a re-distribution of cytotoxic T cells was observed comprising a reduction of T effector memory cells and a concomitant increase of T effector cells. The dynamics of T cell subtypes during immunotherapy prognosticated relapse and survival, in particular among older patients and remained significantly predictive of clinical outcome after correction for potential confounders. Presence of CD8+ T cells with specificity for leukemia-associated antigens identified patients with low relapse risk. Our results point to novel aspects of T cell-mediated immunosurveillance in AML and provide conceivable biomarkers in relapse-preventive immunotherapy. PMID- 26863637 TI - Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide. AB - Malignant gliomas have poor prognosis and urgently require new therapies. Activating Transcription Factor 5 (ATF5) is highly expressed in gliomas, and interference with its expression/function precipitates targeted glioma cell apoptosis in vitro and in vivo. We designed a novel deliverable truncated dominant-negative (d/n) form of ATF5 fused to a cell-penetrating domain (Pen-d/n ATF5-RP) that can be intraperitoneally/subcutaneously administered to mice harboring malignant gliomas generated; (1) by PDGF-B/sh-p53 retroviral transformation of endogenous neural progenitor cells; and (2) by human U87-MG xenografts. In vitro Pen-d/n-ATF5-RP entered into glioma cells and triggered massive apoptosis. In vivo, subcutaneously-administered Pen-d/n-ATF5-RP passed the blood brain barrier, entered normal brain and tumor cells, and then caused rapid selective tumor cell death. MRI verified elimination of retrovirus-induced gliomas within 8-21 days. Histopathology revealed growth-suppression of intracerebral human U87-MG cells xenografts. For endogenous PDGF-B gliomas, there was no recurrence or mortality at 6-12 months versus 66% mortality in controls at 6 months. Necropsy and liver-kidney blood enzyme analysis revealed no adverse effects on brain or other tissues. Our findings thus identify Pen-d/n-ATF5-RP as a potential therapy for malignant gliomas. PMID- 26863638 TI - Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARgamma dependent pathway. AB - Statins (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) are well-established agents to treat hyperlipidemic states. Experimental and epidemiological evidence further implies an anticancer effect of these substances. This study investigates the mechanism underlying human lung cancer cell death by lovastatin and the role of the prostaglandin (PG)-synthesizing enzyme cyclooxygenase-2 (COX-2) in this process. In A549 and H358 lung carcinoma cells the lipophilic prodrug lovastatin lactone led to a concentration-dependent decrease of viability and induction of DNA fragmentation, whereas its HMG-CoA inhibitory, ring-open acid form was inactive in this respect. Apoptotic cell death by lovastatin was accompanied by high intracellular levels of the lactone form, by upregulation of COX-2 mRNA and protein, as well as by increased formation of peroxisome proliferator-activated receptor gamma (PPARgamma) activating PGD2 and 15-deoxy-Delta12,14-PGJ2. Cells were significantly less sensitive to lovastatin-induced apoptotic cell death, when the expression or activity of COX-2 was suppressed by siRNA or by the COX-2 inhibitor NS-398. Apoptosis by lovastatin was likewise reversed by the PPARgamma antagonist GW9662. Fluorescence microscopy analyses revealed a lovastatin-induced cytosol-to-nucleus translocation of PPARgamma that was inhibited by NS-398. Collectively, this study demonstrates COX-2 induction and subsequent COX-2-dependent activation of PPARgamma as a hitherto unknown mechanism by which lovastatin lactone induces human lung cancer cell death. PMID- 26863641 TI - [Not Available]. PMID- 26863639 TI - The prognostic value of pretreatment CA-125 levels and CA-125 normalization in ovarian clear cell carcinoma: a two-academic-institute study. AB - OBJECTIVES: The present study investigated the clinical implications of pretreatment carbohydrate antigen 125 (CA-125) levels and CA-125 normalization in patients with ovarian clear cell carcinoma (CCC), and it provides useful information for the improvement of monitoring strategies for this lethal disease. METHODS: The medical records of patients with ovarian CCC who had undergone primary staging surgery or cytoreductive surgery followed by systemic chemotherapy were retrospectively reviewed. A range of clinico-pathological parameters were collected and examined. RESULTS: A total of 375 women were included in the analysis. FIGO stage (p < 0.001) was identified as the only significant prognostic factor for relapse. Residual tumor and advanced stage (p = 0.001 and p < 0.001, respectively) were identified as independent adverse factors for survival. The potential risk factors associated with elevated pretreatment CA 125 levels included advanced-stage disease, positive residual tumors and negative endometriosis (p < 0.001, p = 0.001 and p <0.001, respectively). Pretreatment CA 125 levels were not associated with relapse-free survival (RFS) or overall survival (OS) (p = 0.060 and p = 0.176, respectively). CA-125 normalization after chemotherapy exhibited a positive linear correlation with advanced stage (r = 0.97, p = 0.001) and residual tumor (r = 0.81, p = 0.027) and a negative relationship with 5-year RFS (r = -0.97, p = 0.002) and 5-year OS (r = -0.97, p= 0.001). Patients with CA-125 levels that normalized before cycle 2 of chemotherapy had a similar prognosis as patients whose CA-125 levels normalized prior to chemotherapy (RFS: p = 0.327; OS: p = 0.654). By contrast, patients with CA-125 levels that normalized after cycle 2 of chemotherapy or never normalized were significantly more likely to experience disease progression. CONCLUSIONS: Pretreatment CA-125 levels are not very useful for predicting clinical outcome. CA-125 levels following treatment are a valid indicator for treatment monitoring. CA-125 normalization after the completion of cycle 1 of chemotherapy represents a distinct inflection point for decreased RFS and OS. PMID- 26863640 TI - Combining complement fixation and luminol chemiluminescence for ultrasensitive detection of avian influenza A rH7N9. AB - The complement fixation test (CFT) is a serological test that can be used to detect the presence of either a specific antibody or antigen to diagnose infections. In a conventional CFT, the assay result is determined by observing the clarity of the reaction solution or the sediment of red cells by the naked eye. Although the assay conditions are thereafter simplified, the sensitivity of the assay would be sacrificed due to the limitation of bulk observation. Inspired by the forensic scientists to examine blood at the scene of the crime, we rationally argued that the luminol chemiluminescence (CL) reaction could be applied in the CFT to sense physiological complement-mediated haemolytic phenomena for sensitive protein detection. The combination of the CFT and the luminol CL system was demonstrated in detection of rH7N9, a recombinant avian influenza virus protein. The testing can be accomplished within 2.5 h and the linear detection range covers 0.25 fg mL(-1) to 25 ng mL(-1). The feasibility of the CL based CFT in assaying a real biopsy was successfully demonstrated by specifically detecting rH7N9 and the carcinoembryonic antigen (CEA) in human serum. This new type of protein detection approach inherits the beauty of complement-mediated assay, such as being fast, and no protein immobilization, blocking and washing. In addition, the participation of luminol CL enables us to quantitatively analyse the intensity of a haemeolysis process, ameliorating the limitation of bulk observation in traditional CFT. It is anticipated that the luminol CL-CFT assay would be particularly suitable for investigation of small molecules, toxins, and short peptides. PMID- 26863642 TI - [The patient with intra-abdominal hypertension]. AB - An intra-abdominal hypertension (IAH) defined as a pathological increase in intra abdominal pressure (IAP) is commonly found on ICU admission or during the ICU stay. Several studies confirmed that an IAH is an independent predictor for mortality of critically ill patients. The abdominal compartment syndrome (ACS) which is defined as a sustained IAP>20 mmHg (with or without an abdominal perfusion pressure [APP]<60mmHg) that is associated with new organ dysfunction or failure has a mortality of up to 60%. In general, an IAH may be induced by several intra-abdominal as well as extra-abdominal conditions. Reduced abdominal wall compliance, intra-abdominal pathologies (either of the peritoneal space or parenchymateous organs) may lead to an IAH. Most commonly, intra-abdominal infections and/or sepsis and severe trauma or burns are predisposing for an IAH. An early sign may be a decrease in urinary output. The effects of an increased IAP on cardiovascular function are well recognized and include negative effects on preload, afterload and contractility. However, all other compartments of the body may be affected by an IAH. Thus, by an increase of the respective compartment pressure, e.g. intracranial pressure, a poly-compartment syndrome may result. Adequate prevention, a forward-looking strategy, and objective techniques for measurement of IAP are required to avoid or early detect an IAH or ACS. Finally, an immediate and consequent interdisciplinary management using conservative, interventional and operative options are necessary to solve an IAH or ACS. PMID- 26863643 TI - [Management of acute pain therapy: guidelines, recommendations and current practice in german hospitals]. AB - Organisational requirements and the education and training of stuff provide the basis for an adequate supply of quality in acute pain and should be the focus of efforts. Although organizational recommendations of the German guideline on "treatment of acute perioperative and post-traumatic pain" have been increasingly established in practice within the last few years, in many German hospitals there is still lagging far behind in the implementation of general supply conditions, such as regular pain measurement or the introduction of appropriate standardized treatment protocols for all areas of the hospital.As specialized care structures acute pain services have been implemented in 80% of the German hospitals, but only 45% of them meet quality criteria. Due to the heterogeneous realization of acute pain management in different hospitals, it comes apparent, that general guideline recommendations and binding definitions are required to achieve adequate supply conditions. PMID- 26863644 TI - Dispersed Hydrogel Actuator for Modiolar Hugging Cochlear Implant Electrode Arrays. AB - OBJECTIVE: Cochlear implants are used in patients with profound deafness due to degeneration of hair cells inside the cochlea. As improvement for commercially available CIs with straight electrode arrays, it is desired that the electrode array hugs toward the nerve cells located at the central axis of the cochlea in order to reduce the stimulation distance. Therefore, we present a hydrogel-based actuated electrode shaft, which should bend itself when exposed to saline solution (simulating the intracochlear liquid perilymph). METHODS: In vitro tests with the electrode arrays were performed in a cochlea model. Different quantities and grain sizes of the hydrogel-building polymer (polyacrylamide) were used to study the self-bending effect. Furthermore, material interfaces between the components were evaluated with scanning electron microscopy, fluorescence microscopy, and an adapted tape test according to DIN EN ISO 2409. RESULTS: Self bending of the electrode array was observed in the cochlea model and a maximum number of 3.1 turns was achieved. No delamination between the components could be observed. CONCLUSION: After insertion, we expect that the electrode shaft moves into a patient individual perimodiolar position without losing its functionality because of a delamination of the components. SIGNIFICANCE: A modiolar hugging electrode design is presented, which may improve hearing restauration with cochlear implants due to an easier insertion technique and a patient individualized hugging to the modiolus. PMID- 26863645 TI - Steerable Catheters in Cardiology: Classifying Steerability and Assessing Future Challenges. AB - OBJECTIVE: This review aims to provide a structured classification of the underlying steering mechanisms in steerable catheters and to assess their future challenges. METHODS: Existing, patented, and experimental designs of steerable catheters are classified with respect to their steerability. Subsequently, the classification is used as a tool for defining future requirements and challenges for steerable cardiac catheters. RESULTS: The results of the classification provide two categories of steering at a fundamental level: 1) Force generation in the tip and 2) force transmission to the tip. The former group consists of force generating steering mechanisms as a result of 1) electric, 2) thermal, and 3) magnetic actuation. The latter group comprises force transmitting steering mechanisms as the result of 4) hydraulic chamber actuation or 5) mechanic cable actuation. Each category can be further subdivided into multiple subcategories. Future requirements and challenges are found for steering and positioning capabilities, cardiac applications and safety, and miniaturization potential. CONCLUSION: A structured classification is presented which identifies the different steering mechanisms in steerable catheters. The classification proves to be a useful tool in determining future requirements and challenges, being invaluable for future application-driven design. SIGNIFICANCE: Using the applied classification as a tool for future design will not only provide insight into previously applied steering technology, it will identify new and unexplored options too. Additionally, insight into the requirements and challenges for catheter steering toward and inside the heart, will allow more dedicated systems, allowing intervention- and patient-specific instrument manipulation. PMID- 26863646 TI - Design and Evaluation of a Catheter Contact-Force Controller for Cardiac Ablation Therapy. AB - GOAL: Maintaining a constant contact force (CF) of an ablation catheter during cardiac catheter ablation therapy is clinically challenging due to inherent myocardial motion, often resulting in poor ablation of arrhythmogenic substrates. To enable a prescribed contact force to be applied during ablation, a catheter contact force controller (CCFC) was developed. METHODS: The system includes a hand-held device attached to a commercial catheter and steerable sheath. A compact linear motor assembly attaches to an ablation catheter and autonomously controls its relative position within the shaft of the steerable sheath. A closed loop control system is implemented within embedded electronics to enable real time catheter-tissue contact force control. To evaluate the performance of the CCFC, a linear motion phantom was used to impose a series of physiological CF profiles; lesion CF was controlled at prescribed levels ranging from 15 to 40 g. RESULTS: For a prescribed CF of 25 g, the CCFC was able to regulate the CF with a root mean squared error of 3.7 +/- 0.7 g. The ability of the CCFC to retract the catheter upon sudden changes in tissue motion, which may have caused tissue damage, was also demonstrated. Finally, the device was able to regulate the CF for a predetermined amount of time according to a force-time integral model. CONCLUSION: The developed CCFC is capable of regulating catheter-tissue CF in a laboratory setting that mimics clinical ablation therapy. SIGNIFICANCE: Catheter tissue CF control promises to improve the precision and success of ablation lesion delivery. PMID- 26863647 TI - Spatio-Temporal Matching for Human Pose Estimation in Video. AB - Detection and tracking humans in videos have been long-standing problems in computer vision. Most successful approaches (e.g., deformable parts models) heavily rely on discriminative models to build appearance detectors for body joints and generative models to constrain possible body configurations (e.g., trees). While these 2D models have been successfully applied to images (and with less success to videos), a major challenge is to generalize these models to cope with camera views. In order to achieve view-invariance, these 2D models typically require a large amount of training data across views that is difficult to gather and time-consuming to label. Unlike existing 2D models, this paper formulates the problem of human detection in videos as spatio-temporal matching (STM) between a 3D motion capture model and trajectories in videos. Our algorithm estimates the camera view and selects a subset of tracked trajectories that matches the motion of the 3D model. The STM is efficiently solved with linear programming, and it is robust to tracking mismatches, occlusions and outliers. To the best of our knowledge this is the first paper that solves the correspondence between video and 3D motion capture data for human pose detection. Experiments on the CMU motion capture, Human3.6M, Berkeley MHAD and CMU MAD databases illustrate the benefits of our method over state-of-the-art approaches. PMID- 26863650 TI - High-Frame-Rate Echocardiography Using Coherent Compounding With Doppler-Based Motion-Compensation. AB - High-frame-rate ultrasonography based on coherent compounding of unfocused beams can potentially transform the assessment of cardiac function. As it requires successive waves to be combined coherently, this approach is sensitive to high velocity tissue motion. We investigated coherent compounding of tilted diverging waves, emitted from a 2.5 MHz clinical phased array transducer. To cope with high myocardial velocities, a triangle transmit sequence of diverging waves is proposed, combined with tissue Doppler imaging to perform motion compensation (MoCo). The compound sequence with integrated MoCo was adjusted from simulations and was tested in vitro and in vivo. Realistic myocardial velocities were analyzed in an in vitro spinning disk with anechoic cysts. While a 8 dB decrease (no motion versus high motion) was observed without MoCo, the contrast-to-noise ratio of the cysts was preserved with the MoCo approach. With this method, we could provide high-quality in vivo B-mode cardiac images with tissue Doppler at 250 frames per second. Although the septum and the anterior mitral leaflet were poorly apparent without MoCo, they became well perceptible and well contrasted with MoCo. The septal and lateral mitral annulus velocities determined by tissue Doppler were concordant with those measured by pulsed-wave Doppler with a clinical scanner (r(2)=0.7,y=0.9 x+0.5,N=60) . To conclude, high-contrast echo cardiographic B-mode and tissue Doppler images can be obtained with diverging beams when motion compensation is integrated in the coherent compounding process. PMID- 26863649 TI - Automated Real-Time Conjunctival Microvasculature Image Stabilization. AB - The bulbar conjunctiva is a thin, vascularized membrane covering the sclera of the eye. Non-invasive imaging techniques have been utilized to assess the conjunctival vasculature as a means of studying microcirculatory hemodynamics. However, eye motion often confounds quantification of these hemodynamic properties. In the current study, we present a novel optical imaging system for automated stabilization of conjunctival microvasculature images by real-time eye motion tracking and realignment of the optical path. The ability of the system to stabilize conjunctival images acquired over time by reducing image displacements and maintaining the imaging area was demonstrated. PMID- 26863651 TI - Constrained Statistical Modelling of Knee Flexion From Multi-Pose Magnetic Resonance Imaging. AB - Reconstruction of the anterior cruciate ligament (ACL) through arthroscopy is one of the most common procedures in orthopaedics. It requires accurate alignment and drilling of the tibial and femoral tunnels through which the ligament graft is attached. Although commercial computer-assisted navigation systems exist to guide the placement of these tunnels, most of them are limited to a fixed pose without due consideration of dynamic factors involved in different knee flexion angles. This paper presents a new model for intraoperative guidance of arthroscopic ACL reconstruction with reduced error particularly in the ligament attachment area. The method uses 3D preoperative data at different flexion angles to build a subject-specific statistical model of knee pose. To circumvent the problem of limited training samples and ensure physically meaningful pose instantiation, homogeneous transformations between different poses and local-deformation finite element modelling are used to enlarge the training set. Subsequently, an anatomical geodesic flexion analysis is performed to extract the subject-specific flexion characteristics. The advantages of the method were also tested by detailed comparison to standard Principal Component Analysis (PCA), nonlinear PCA without training set enlargement, and other state-of-the-art articulated joint modelling methods. The method yielded sub-millimetre accuracy, demonstrating its potential clinical value. PMID- 26863652 TI - Multi-Instance Deep Learning: Discover Discriminative Local Anatomies for Bodypart Recognition. AB - In general image recognition problems, discriminative information often lies in local image patches. For example, most human identity information exists in the image patches containing human faces. The same situation stays in medical images as well. "Bodypart identity" of a transversal slice-which bodypart the slice comes from-is often indicated by local image information, e.g., a cardiac slice and an aorta arch slice are only differentiated by the mediastinum region. In this work, we design a multi-stage deep learning framework for image classification and apply it on bodypart recognition. Specifically, the proposed framework aims at: 1) discover the local regions that are discriminative and non informative to the image classification problem, and 2) learn a image-level classifier based on these local regions. We achieve these two tasks by the two stages of learning scheme, respectively. In the pre-train stage, a convolutional neural network (CNN) is learned in a multi-instance learning fashion to extract the most discriminative and and non-informative local patches from the training slices. In the boosting stage, the pre-learned CNN is further boosted by these local patches for image classification. The CNN learned by exploiting the discriminative local appearances becomes more accurate than those learned from global image context. The key hallmark of our method is that it automatically discovers the discriminative and non-informative local patches through multi instance deep learning. Thus, no manual annotation is required. Our method is validated on a synthetic dataset and a large scale CT dataset. It achieves better performances than state-of-the-art approaches, including the standard deep CNN. PMID- 26863653 TI - Feasibility of Swept Synthetic Aperture Ultrasound Imaging. AB - Ultrasound image quality is often inherently limited by the physical dimensions of the imaging transducer. We hypothesize that, by collecting synthetic aperture data sets over a range of aperture positions while precisely tracking the position and orientation of the transducer, we can synthesize large effective apertures to produce images with improved resolution and target detectability. We analyze the two largest limiting factors for coherent signal summation: aberration and mechanical uncertainty. Using an excised canine abdominal wall as a model phase screen, we experimentally observed an effective arrival time error ranging from 18.3 ns to 58 ns (root-mean-square error) across the swept positions. Through this clutter-generating tissue, we observed a 72.9% improvement in resolution with only a 3.75 dB increase in side lobe amplitude compared to the control case. We present a simulation model to study the effect of calibration and mechanical jitter errors on the synthesized point spread function. The relative effects of these errors in each imaging dimension are explored, showing the importance of orientation relative to the point spread function. We present a prototype device for performing swept synthetic aperture imaging using a conventional 1-D array transducer and ultrasound research scanner. Point target reconstruction error for a 44.2 degree sweep shows a reconstruction precision of 82.8 MUm and 17.8 MUm in the lateral and axial dimensions respectively, within the acceptable performance bounds of the simulation model. Improvements in resolution, contrast and contrast-to-noise ratio are demonstrated in vivo and in a fetal phantom. PMID- 26863654 TI - Locality Sensitive Deep Learning for Detection and Classification of Nuclei in Routine Colon Cancer Histology Images. AB - Detection and classification of cell nuclei in histopathology images of cancerous tissue stained with the standard hematoxylin and eosin stain is a challenging task due to cellular heterogeneity. Deep learning approaches have been shown to produce encouraging results on histopathology images in various studies. In this paper, we propose a Spatially Constrained Convolutional Neural Network (SC-CNN) to perform nucleus detection. SC-CNN regresses the likelihood of a pixel being the center of a nucleus, where high probability values are spatially constrained to locate in the vicinity of the centers of nuclei. For classification of nuclei, we propose a novel Neighboring Ensemble Predictor (NEP) coupled with CNN to more accurately predict the class label of detected cell nuclei. The proposed approaches for detection and classification do not require segmentation of nuclei. We have evaluated them on a large dataset of colorectal adenocarcinoma images, consisting of more than 20,000 annotated nuclei belonging to four different classes. Our results show that the joint detection and classification of the proposed SC-CNN and NEP produces the highest average F1 score as compared to other recently published approaches. Prospectively, the proposed methods could offer benefit to pathology practice in terms of quantitative analysis of tissue constituents in whole-slide images, and potentially lead to a better understanding of cancer. PMID- 26863655 TI - OSSI-PET: Open-Access Database of Simulated [(11)C]Raclopride Scans for the Inveon Preclinical PET Scanner: Application to the Optimization of Reconstruction Methods for Dynamic Studies. AB - A wide range of medical imaging applications benefits from the availability of realistic ground truth data. In the case of positron emission tomography (PET), ground truth data is crucial to validate processing algorithms and assessing their performances. The design of such ground truth data often relies on Monte Carlo simulation techniques. Since the creation of a large dataset is not trivial both in terms of computing time and realism, we propose the OSSI-PET database containing 350 simulated [(11)C]Raclopride dynamic scans for rats, created specifically for the Inveon pre-clinical PET scanner. The originality of this database lies on the availability of several groups of scans with controlled biological variations in the striata. Besides, each group consists of a large number of realizations (i.e., noise replicates). We present the construction methodology of this database using rat pharmacokinetic and anatomical models. A first application using the OSSI-PET database is presented. Several commonly used reconstruction techniques were compared in terms of image quality, accuracy and variability of the activity estimates and of the computed kinetic parameters. The results showed that OP-OSEM3D iterative reconstruction method outperformed the other tested methods. Analytical methods such as FBP2D and 3DRP also produced satisfactory results. However, FORE followed by OSEM2D reconstructions should be avoided. Beyond the illustration of the potential of the database, this application will help scientists to understand the different sources of noise and bias that can occur at the different steps in the processing and will be very useful for choosing appropriate reconstruction methods and parameters. PMID- 26863656 TI - Delay Estimation Using Instantaneous Frequency and Phase Difference--Simulation Study. AB - We propose a time-domain delay estimator that takes the slope of the best fit line crossing the origin in the instantaneous frequency-phase difference plane as the delay estimate. This formulation differs from existing phase-based estimators in two respects. First, we find the instantaneous frequency at all individual sample points, including large and abrupt spikes caused by destructive interference in the coherent scattering process. This differs from Loupas which finds a smoothed-out center frequency estimate within an observation window. We show that under high signal-to-noise ratio (SNR), the information from these spikes can be properly used. Second, we show that error ought to be considered as the deviation of the phase difference from the best fit line rather than deviation from the averaged phase difference. Without considering instantaneous frequency, phase-based estimators make the following two errors: samples with phase difference far away from the center frequency need not be errors as they naturally have large phase difference when their instantaneous frequency is large; samples with phase difference close to the center frequency may in fact be errors if their instantaneous frequency is large. We derive the Gauss-Markov least-squares best fit line and then propose an iterative variant that removes samples from the line-fitting process if its deviation from the best fit line is sufficiently large. The iterative version can reduce the effect of aliasing for larger delays and also further reduce the root-mean-square error (RMSE) of the estimate. Simulation studies using various bandwidth, SNR, and delay parameters indicate that iterative phase least squares (PLS) begins to outperform correlation phase Loupas at between SNR of 30 dB (for larger bandwidths and larger delays) and 60 dB (for smaller bandwidths and smaller delays). As SNR increases, iterative PLS can reach a 30- to 50-dB increase in performance over correlation phase Loupas with respect to RMSE in the most favorable conditions. PMID- 26863657 TI - Frequency Comparison of [Formula: see text] Ion Optical Clocks at PTB and NPL via GPS PPP. AB - We used precise point positioning, a well-established GPS carrier-phase frequency transfer method to perform a direct remote comparison of two optical frequency standards based on single laser-cooled [Formula: see text] ions operated at the National Physical Laboratory (NPL), U.K. and the Physikalisch-Technische Bundesanstalt (PTB), Germany. At both institutes, an active hydrogen maser serves as a flywheel oscillator which is connected to a GPS receiver as an external frequency reference and compared simultaneously to a realization of the unperturbed frequency of the (2)S1/2(F=0)-(2)D3/2(F=2) electric quadrupole transition in [Formula: see text] via an optical femtosecond frequency comb. To profit from long coherent GPS-link measurements, we extrapolate the fractional frequency difference over the various data gaps in the optical clock to maser comparisons which introduces maser noise to the frequency comparison but improves the uncertainty from the GPS-link instability. We determined the total statistical uncertainty consisting of the GPS-link uncertainty and the extrapolation uncertainties for several extrapolation schemes. Using the extrapolation scheme with the smallest combined uncertainty, we find a fractional frequency difference [Formula: see text] of -1.3*10(-15) with a combined uncertainty of 1.2*10(-15) for a total measurement time of 67 h. This result is consistent with an agreement of the frequencies realized by both optical clocks and with recent absolute frequency measurements against caesium fountain clocks within the corresponding uncertainties. PMID- 26863658 TI - Equivalent Circuit Models for Large Arrays of Curved and Flat Piezoelectric Micromachined Ultrasonic Transducers. AB - Equivalent circuit models of large arrays of curved (spherical shape) and flat piezoelectric micromachined ultrasonic transducers (pMUTs) have been developed for complex pMUT arrays design and analysis. The exact solutions for circuit parameters in the electromechanical domain, such as mechanical admittance, input electrical impedance, and electromechanical transformer ratio, were analytically derived. By utilizing the array solution methods previously established for the thickness-mode piezoelectric devices and capacitive micromachined ultrasonic transducers (cMUTs), the single pMUT circuit model can be extended to models for array structures. The array model includes both the self- and mutual-acoustic radiation impedances of individual transducers in the acoustic medium. Volumetric displacement, induced piezoelectric current, and pressure field can be derived with respect to the input voltage matrix, material, and geometrical properties of each individual transducer and the array structure. As such, the analytical models presented here can be used as a guideline for analyses and design evaluations of large arrays of curved and flat pMUTs efficiently and can be further generalized to evaluate other pMUT architectures in the form of single devices or arrays. PMID- 26863660 TI - Local Rademacher Complexity for Multi-Label Learning. AB - We analyze the local Rademacher complexity of empirical risk minimization-based multi-label learning algorithms, and in doing so propose a new algorithm for multi-label learning. Rather than using the trace norm to regularize the multi label predictor, we instead minimize the tail sum of the singular values of the predictor in multi-label learning. Benefiting from the use of the local Rademacher complexity, our algorithm, therefore, has a sharper generalization error bound. Compared with methods that minimize over all singular values, concentrating on the tail singular values results in better recovery of the low rank structure of the multi-label predictor, which plays an important role in exploiting label correlations. We propose a new conditional singular value thresholding algorithm to solve the resulting objective function. Moreover, a variance control strategy is employed to reduce the variance of variables in optimization. Empirical studies on real-world data sets validate our theoretical results and demonstrate the effectiveness of the proposed algorithm for multi label learning. PMID- 26863659 TI - Bubble-Induced Color Doppler Feedback for Histotripsy Tissue Fractionation. AB - Histotripsy therapy produces cavitating bubble clouds to increasingly fractionate and eventually liquefy tissue using high-intensity ultrasound pulses. Following cavitation generated by each pulse, coherent motion of the cavitation residual nuclei can be detected using metrics formed from ultrasound color Doppler acquisitions. In this paper, three experiments were performed to investigate the characteristics of this motion as real-time feedback on histotripsy tissue fractionation. In the first experiment, bubble-induced color Doppler (BCD) and particle image velocimetry (PIV) analysis monitored the residual cavitation nuclei in the treatment region in an agarose tissue phantom treated with two cycle histotripsy pulses at [Formula: see text] using a 500-kHz transducer. Both BCD and PIV results showed brief chaotic motion of the residual nuclei followed by coherent motion first moving away from the transducer and then rebounding back. Velocity measurements from both PIV and BCD agreed well, showing a monotonic increase in rebound time up to a saturation point for increased therapy dose. In a second experiment, a thin layer of red blood cells (RBC) was added to the phantom to allow quantification of the fractionation of the RBC layer to compare with BCD metrics. A strong linear correlation was observed between the fractionation level and the time to BCD peak rebound velocity over histotripsy treatment. Finally, the correlation between BCD feedback and histotripsy tissue fractionation was validated in ex vivo porcine liver evaluated histologically. BCD metrics showed strong linear correlation with fractionation progression, suggesting that BCD provides useful quantitative real-time feedback on histotripsy treatment progression. PMID- 26863661 TI - Robust Multi-Focus Image Fusion Using Multi-Task Sparse Representation and Spatial Context. AB - We present a novel fusion method based on a multi-task robust sparse representation (MRSR) model and spatial context information to address the fusion of multi-focus gray-level images with misregistration. First, we present a robust sparse representation (RSR) model by replacing the conventional least-squared reconstruction error by a sparse reconstruction error. We then propose a multi task version of the RSR model, viz., the MRSR model. The latter is then applied to multi-focus image fusion by employing the detailed information regarding each image patch and its spatial neighbors to collaboratively determine both the focused and defocused regions in the input images. To achieve this, we formulate the problem of extracting details from multiple image patches as a joint multi task sparsity pursuit based on the MRSR model. Experimental results demonstrate that the suggested algorithm is competitive with the current state-of-the-art and superior to some approaches that use traditional sparse representation methods when input images are misregistered. PMID- 26863662 TI - Filtering Chromatic Aberration for Wide Acceptance Angle Electrostatic Lenses II- Experimental Evaluation and Software-Based Imaging Energy Analyzer. AB - Here, the experimental results of the method of filtering the effect of chromatic aberration for wide acceptance angle electrostatic lens-based system are described. This method can eliminate the effect of chromatic aberration from the images of a measured spectral image sequence by determining and removing the effect of higher and lower kinetic energy electrons on each different energy image, which leads to significant improvement of image and spectral quality. The method is based on the numerical solution of a large system of linear equations and equivalent with a multivariate strongly nonlinear deconvolution method. A matrix whose elements describe the strongly nonlinear chromatic aberration related transmission function of the lens system acts on the vector of the ordered pixels of the distortion free spectral image sequence, and produces the vector of the ordered pixels of the measured spectral image sequence. Since the method can be applied not only on 2D real- and $k$ -space diffraction images, but also along a third dimension of the image sequence that is along the optical or in the 3D parameter space, the energy axis, it functions as a software-based imaging energy analyzer (SBIEA). It can also be applied in cases of light or other type of optics for different optical aberrations and distortions. In case of electron optics, the SBIEA method makes possible the spectral imaging without the application of any other energy filter. It is notable that this method also eliminates the disturbing background significantly in the present investigated case of reflection electron energy loss spectra. It eliminates the instrumental effects and makes possible to measure the real physical processes better. PMID- 26863664 TI - A 3D Steganalytic Algorithm and Steganalysis-Resistant Watermarking. AB - We propose a simple yet efficient steganalytic algorithm for watermarks embedded by two state-of-the-art 3D watermarking algorithms by Cho et al. The main observation is that while in a clean model the means/variances of Cho et al.'s normalized histogram bins are expected to follow a Gaussian distribution, in a marked model their distribution will be bimodal. The proposed algorithm estimates the number of bins through an exhaustive search and then the presence of a watermark is decided by a tailor made normality test or a t-test. We also propose a modification of Cho et al.'s watermarking algorithms with the watermark embedded by changing the histogram of the radial coordinates of the vertices. Rather than targeting a continuous statistics such as the mean or variance of the values in a bin, the proposed watermarking modifies a discrete statistic, which here is the height of the histogram bin, to achieve watermark embedding. Experimental results demonstrate that the modified algorithm offers not only better resistance against the steganalytic attack we developed, but also an improved robustness/capacity trade-off. PMID- 26863663 TI - Comprehensive Modeling and Visualization of Cardiac Anatomy and Physiology from CT Imaging and Computer Simulations. AB - In clinical cardiology, both anatomy and physiology are needed to diagnose cardiac pathologies. CT imaging and computer simulations provide valuable and complementary data for this purpose. However, it remains challenging to gain useful information from the large amount of high-dimensional diverse data. The current tools are not adequately integrated to visualize anatomic and physiologic data from a complete yet focused perspective. We introduce a new computer-aided diagnosis framework, which allows for comprehensive modeling and visualization of cardiac anatomy and physiology from CT imaging data and computer simulations, with a primary focus on ischemic heart disease. The following visual information is presented: (1) Anatomy from CT imaging: geometric modeling and visualization of cardiac anatomy, including four heart chambers, left and right ventricular outflow tracts, and coronary arteries; (2) Function from CT imaging: motion modeling, strain calculation, and visualization of four heart chambers; (3) Physiology from CT imaging: quantification and visualization of myocardial perfusion and contextual integration with coronary artery anatomy; (4) Physiology from computer simulation: computation and visualization of hemodynamics (e.g., coronary blood velocity, pressure, shear stress, and fluid forces on the vessel wall). Substantially, feedback from cardiologists have confirmed the practical utility of integrating these features for the purpose of computer-aided diagnosis of ischemic heart disease. PMID- 26863665 TI - Manga Vectorization and Manipulation with Procedural Simple Screentone. AB - Manga are a popular artistic form around the world, and artists use simple line drawing and screentone to create all kinds of interesting productions. Vectorization is helpful to digitally reproduce these elements for proper content and intention delivery on electronic devices. Therefore, this study aims at transforming scanned Manga to a vector representation for interactive manipulation and real-time rendering with arbitrary resolution. Our system first decomposes the patch into rough Manga elements including possible borders and shading regions using adaptive binarization and screentone detector. We classify detected screentone into simple and complex patterns: our system extracts simple screentone properties for refining screentone borders, estimating lighting, compensating missing strokes inside screentone regions, and later resolution independently rendering with our procedural shaders. Our system treats the others as complex screentone areas and vectorizes them with our proposed line tracer which aims at locating boundaries of all shading regions and polishing all shading borders with the curve-based Gaussian refiner. A user can lay down simple scribbles to cluster Manga elements intuitively for the formation of semantic components, and our system vectorizes these components into shading meshes along with embedded Bezier curves as a unified foundation for consistent manipulation including pattern manipulation, deformation, and lighting addition. Our system can real-time and resolution independently render the shading regions with our procedural shaders and drawing borders with the curve-based shader. For Manga manipulation, the proposed vector representation can be not only magnified without artifacts but also deformed easily to generate interesting results. PMID- 26863666 TI - Deformable Model-Based Methods for Shape Control of a Haptic Jamming Surface. AB - Haptic Jamming, the approach of simultaneously controlling mechanical properties and surface deformation of a tactile display via particle jamming and pneumatics, shows promise as a tangible, shape-changing human-computer interface. Previous research introduced device design and described the force-displacement interactions for individual jamming cells. The work in this article analyzes the shape output capabilities of a multi-cell array. A spring-mass deformable body simulation combines models of the three actuation inputs of a Haptic Jamming surface: node pinning, chamber pressurization, and cell jamming. Surface measurements of a 12-cell prototype from a depth camera fit the mass and stiffness parameters to the device during pressurization tests and validate the accuracy of the model for various actuation sequences. The simulator is used to develop an algorithm that generates a sequence of actuation inputs for a Haptic Jamming array of any size in order to match a desired surface output shape. Data extracted from topographical maps and three-dimensional solid object models are used to evaluate the shape-matching algorithm and assess the utility of increasing array size and resolution. Results show that a discrete Laplace operator applied to the input is a suitable predictor of the correlation coefficient between the desired shape and the device output. PMID- 26863667 TI - Automatic Parametrization of Somatosensory Evoked Potentials With Chirp Modeling. AB - In this paper, an approach using polynomial phase chirp signals to model somatosensory evoked potentials (SEPs) is proposed. SEP waveforms are assumed as impulses undergoing group velocity dispersion while propagating along a multipath neural connection. Mathematical analysis of pulse dispersion resulting in chirp signals is performed. An automatic parameterization of SEPs is proposed using chirp models. A Particle Swarm Optimization algorithm is used to optimize the model parameters. Features describing the latencies and amplitudes of SEPs are automatically derived. A rat model is then used to evaluate the automatic parameterization of SEPs in two experimental cases, i.e., anesthesia level and spinal cord injury (SCI). Experimental results show that chirp-based model parameters and the derived SEP features are significant in describing both anesthesia level and SCI changes. The proposed automatic optimization based approach for extracting chirp parameters offers potential for detailed SEP analysis in future studies. The method implementation in Matlab technical computing language is provided online. PMID- 26863668 TI - A General, Adaptive, Roadmap-Based Algorithm for Protein Motion Computation. AB - Precious information on protein function can be extracted from a detailed characterization of protein equilibrium dynamics. This remains elusive in wet and dry laboratories, as function-modulating transitions of a protein between functionally-relevant, thermodynamically-stable and meta-stable structural states often span disparate time scales. In this paper we propose a novel, robotics inspired algorithm that circumvents time-scale challenges by drawing analogies between protein motion and robot motion. The algorithm adapts the popular roadmap based framework in robot motion computation to handle the more complex protein conformation space and its underlying rugged energy surface. Given known structures representing stable and meta-stable states of a protein, the algorithm yields a time- and energy-prioritized list of transition paths between the structures, with each path represented as a series of conformations. The algorithm balances computational resources between a global search aimed at obtaining a global view of the network of protein conformations and their connectivity and a detailed local search focused on realizing such connections with physically-realistic models. Promising results are presented on a variety of proteins that demonstrate the general utility of the algorithm and its capability to improve the state of the art without employing system-specific insight. PMID- 26863669 TI - A Comparative Analysis Between k-Mers and Community Detection-Based Features for the Task of Protein Classification. AB - Machine learning algorithms are widely used to annotate biological sequences. Low dimensional informative feature vectors can be crucial for the performance of the algorithms. In prior work, we have proposed the use of a community detection approach to construct low dimensional feature sets for nucleotide sequence classification. Our approach used the Hamming distance between short nucleotide subsequences, called k-mers, to construct a network, and subsequently used community detection to identify groups of k -mers that appear frequently in a set of sequences. Whereas this approach worked well for nucleotide sequence classification, it could not be directly used for protein sequences, as the Hamming distance is not a good measure for comparing short protein k-mers. To address this limitation, we extended our prior approach by replacing the Hamming distance with substitution scores. Experimental results in different learning scenarios show that the features generated with the new approach are more informative than k-mers. PMID- 26863671 TI - Multiple Fingers - One Gestalt. AB - The Gestalt theory of perception offered principles by which distributed visual sensations are combined into a structured experience ("Gestalt"). We demonstrate conditions whereby haptic sensations at two fingertips are integrated in the perception of a single object. When virtual bumps were presented simultaneously to the right hand's thumb and index finger during lateral arm movements, participants reported perceiving a single bump. A discrimination task measured the bump's perceived location and perceptual reliability (assessed by differential thresholds) for four finger configurations, which varied in their adherence to the Gestalt principles of proximity (small versus large finger separation) and synchrony (virtual spring to link movements of the two fingers versus no spring). According to models of integration, reliability should increase with the degree to which multi-finger cues integrate into a unified percept. Differential thresholds were smaller in the virtual-spring condition (synchrony) than when fingers were unlinked. Additionally, in the condition with reduced synchrony, greater proximity led to lower differential thresholds. Thus, with greater adherence to Gestalt principles, thresholds approached values predicted for optimal integration. We conclude that the Gestalt principles of synchrony and proximity apply to haptic perception of surface properties and that these principles can interact to promote multi-finger integration. PMID- 26863672 TI - An Integrated Learning and Filtering Approach for Fault Diagnosis of a Class of Nonlinear Dynamical Systems. AB - This paper develops an integrated filtering and adaptive approximation-based approach for fault diagnosis of process and sensor faults in a class of continuous-time nonlinear systems with modeling uncertainties and measurement noise. The proposed approach integrates learning with filtering techniques to derive tight detection thresholds, which is accomplished in two ways: 1) by learning the modeling uncertainty through adaptive approximation methods and 2) by using filtering for dampening measurement noise. Upon the detection of a fault, two estimation models, one for process and the other for sensor faults, are initiated in order to identify the type of fault. Each estimation model utilizes learning to estimate the potential fault that has occurred, and adaptive isolation thresholds for each estimation model are designed. The fault type is deduced based on an exclusion-based logic, and fault detectability and identification conditions are rigorously derived, characterizing quantitatively the class of faults that can be detected and identified by the proposed scheme. Finally, simulation results are used to demonstrate the effectiveness of the proposed approach. PMID- 26863670 TI - Smart Multi-Frequency Bioelectrical Impedance Spectrometer for BIA and BIVA Applications. AB - Bioelectrical impedance analysis (BIA) is a noninvasive and commonly used method for the assessment of body composition including body water. We designed a small, portable and wireless multi-frequency impedance spectrometer based on the 12 bit impedance network analyzer AD5933 and a precision wide-band constant current source for tetrapolar whole body impedance measurements. The impedance spectrometer communicates via Bluetooth with mobile devices (smart phone or tablet computer) that provide user interface for patient management and data visualization. The export of patient measurement results into a clinical research database facilitates the aggregation of bioelectrical impedance analysis and biolectrical impedance vector analysis (BIVA) data across multiple subjects and/or studies. The performance of the spectrometer was evaluated using a passive tissue equivalent circuit model as well as a comparison of body composition changes assessed with bioelectrical impedance and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Our results show an absolute error of 1% for resistance and 5% for reactance measurements in the frequency range of 3 kHz to 150 kHz. A linear regression of BIA and DXA fat mass estimations showed a strong correlation (r(2)=0.985) between measures with a maximum absolute error of 6.5%. The simplicity of BIA measurements, a cost effective design and the simple visual representation of impedance data enables patients to compare and determine body composition during the time course of a specific treatment plan in a clinical or home environment. PMID- 26863673 TI - An Optimization-Based Method for Feature Ranking in Nonlinear Regression Problems. AB - In this paper, we consider the feature ranking problem, where, given a set of training instances, the task is to associate a score with the features in order to assess their relevance. Feature ranking is a very important tool for decision support systems, and may be used as an auxiliary step of feature selection to reduce the high dimensionality of real-world data. We focus on regression problems by assuming that the process underlying the generated data can be approximated by a continuous function (for instance, a feedforward neural network). We formally state the notion of relevance of a feature by introducing a minimum zero-norm inversion problem of a neural network, which is a nonsmooth, constrained optimization problem. We employ a concave approximation of the zero norm function, and we define a smooth, global optimization problem to be solved in order to assess the relevance of the features. We present the new feature ranking method based on the solution of instances of the global optimization problem depending on the available training data. Computational experiments on both artificial and real data sets are performed, and point out that the proposed feature ranking method is a valid alternative to existing methods in terms of effectiveness. The obtained results also show that the method is costly in terms of CPU time, and this may be a limitation in the solution of large-dimensional problems. PMID- 26863675 TI - Speeding Up Cellular Neural Network Processing Ability by Embodying Memristors. AB - Cellular neural networks (CNNs) are an efficient tool for image analysis and pattern recognition. Based on elementary cells connected to neighboring units, they are easy to install in hardware, carrying out massively parallel processes. This brief presents a new model of CNN with memory devices, which enhances further CNN performance. By introducing a memristive element in basic cells, we carry out different experiments, allowing the analysis of the functions traditionally carried out by the standard CNN. Without modifying the templates considered by the scientific literature, this simple variation originates a significant improvement in ~ 30 % of performances in pattern recognition and image processing. These progresses were experimentally calculated on the time the system requires to reach a fixed point. Moreover, the different role that each parameter has in the developed method was also analyzed to better understand the complex processing ability of these systems. PMID- 26863674 TI - Model-Based Reinforcement Learning for Infinite-Horizon Approximate Optimal Tracking. AB - This brief paper provides an approximate online adaptive solution to the infinite horizon optimal tracking problem for control-affine continuous-time nonlinear systems with unknown drift dynamics. To relax the persistence of excitation condition, model-based reinforcement learning is implemented using a concurrent learning-based system identifier to simulate experience by evaluating the Bellman error over unexplored areas of the state space. Tracking of the desired trajectory and convergence of the developed policy to a neighborhood of the optimal policy are established via Lyapunov-based stability analysis. Simulation results demonstrate the effectiveness of the developed technique. PMID- 26863676 TI - Multiscale Support Vector Learning With Projection Operator Wavelet Kernel for Nonlinear Dynamical System Identification. AB - A giant leap has been made in the past couple of decades with the introduction of kernel-based learning as a mainstay for designing effective nonlinear computational learning algorithms. In view of the geometric interpretation of conditional expectation and the ubiquity of multiscale characteristics in highly complex nonlinear dynamic systems [1]-[3], this paper presents a new orthogonal projection operator wavelet kernel, aiming at developing an efficient computational learning approach for nonlinear dynamical system identification. In the framework of multiresolution analysis, the proposed projection operator wavelet kernel can fulfill the multiscale, multidimensional learning to estimate complex dependencies. The special advantage of the projection operator wavelet kernel developed in this paper lies in the fact that it has a closed-form expression, which greatly facilitates its application in kernel learning. To the best of our knowledge, it is the first closed-form orthogonal projection wavelet kernel reported in the literature. It provides a link between grid-based wavelets and mesh-free kernel-based methods. Simulation studies for identifying the parallel models of two benchmark nonlinear dynamical systems confirm its superiority in model accuracy and sparsity. PMID- 26863677 TI - Air-Breathing Hypersonic Vehicle Tracking Control Based on Adaptive Dynamic Programming. AB - In this paper, we propose a data-driven supplementary control approach with adaptive learning capability for air-breathing hypersonic vehicle tracking control based on action-dependent heuristic dynamic programming (ADHDP). The control action is generated by the combination of sliding mode control (SMC) and the ADHDP controller to track the desired velocity and the desired altitude. In particular, the ADHDP controller observes the differences between the actual velocity/altitude and the desired velocity/altitude, and then provides a supplementary control action accordingly. The ADHDP controller does not rely on the accurate mathematical model function and is data driven. Meanwhile, it is capable to adjust its parameters online over time under various working conditions, which is very suitable for hypersonic vehicle system with parameter uncertainties and disturbances. We verify the adaptive supplementary control approach versus the traditional SMC in the cruising flight, and provide three simulation studies to illustrate the improved performance with the proposed approach. PMID- 26863678 TI - An Adaptable Continuous Restricted Boltzmann Machine in VLSI for Fusing the Sensory Data of an Electronic Nose. AB - An embedded system capable of fusing sensory data is demanded for many portable or implantable microsystems. The continuous restricted Boltzmann machine (CRBM) is a probabilistic neural network not only capable of classifying data reliably but also amenable to very-large-scale-integration (VLSI) implementation. Although the embedded system based on the CRBM has been demonstrated with analog VLSI, the precision required by the learning algorithm is hardly achievable with analog circuits. Therefore, this paper investigates the feasibility of realizing the CRBM as a digital embedded system for fusing the sensory data of an electronic nose (eNose). The fusion here refers to data clustering and dimensional reduction that facilitates reliable classification. The capability of the CRBM to model different types of eNose data is first examined by MATLAB simulation. Afterward, the CRBM algorithm is customdesigned as a digital embedded system within an eNose microsystem. The functionality of the embedded CRBM system is then tested and discussed. With on-chip learning ability, the CRBM-embedded eNose is able to adapt its parameters in response to new data inputs or environmental changes. PMID- 26863679 TI - Scalable Algorithms for Multi-Instance Learning. AB - Multi-instance learning (MIL) has been widely applied to diverse applications involving complicated data objects, such as images and genes. However, most existing MIL algorithms can only handle small- or moderate-sized data. In order to deal with large-scale MIL problems, we propose MIL based on the vector of locally aggregated descriptors representation (miVLAD) and MIL based on the Fisher vector representation (miFV), two efficient and scalable MIL algorithms. They map the original MIL bags into new vector representations using their corresponding mapping functions. The new feature representations keep essential bag-level information, and at the same time lead to excellent MIL performances even when linear classifiers are used. Thanks to the low computational cost in the mapping step and the scalability of linear classifiers, miVLAD and miFV can handle large-scale MIL data efficiently and effectively. Experiments show that miVLAD and miFV not only achieve comparable accuracy rates with the state-of-the art MIL algorithms, but also have hundreds of times faster speed. Moreover, we can regard the new miVLAD and miFV representations as multiview data, which improves the accuracy rates in most cases. In addition, our algorithms perform well even when they are used without parameter tuning (i.e., adopting the default parameters), which is convenient for practical MIL applications. PMID- 26863680 TI - Max-Margin-Based Discriminative Feature Learning. AB - In this brief, we propose a new max-margin-based discriminative feature learning method. In particular, we aim at learning a low-dimensional feature representation, so as to maximize the global margin of the data and make the samples from the same class as close as possible. In order to enhance the robustness to noise, we leverage a regularization term to make the transformation matrix sparse in rows. In addition, we further learn and leverage the correlations among multiple categories for assisting in learning discriminative features. The experimental results demonstrate the power of the proposed method against the related state-of-the-art methods. PMID- 26863681 TI - Motion Artifact Suppression in Impedance Pneumography Signal for Portable Monitoring of Respiration: An Adaptive Approach. AB - The focus of this paper is motion artifact (MA) reduction from the impedance pneumography (IP) signal, which is widely used to monitor respiration. The amplitude of the MA that contaminates the IP signal is often much larger than the amplitude of the respiratory component of the signal. Moreover, the morphology and frequency composition of the artifacts may be very similar to that of the respiration, making it difficult to remove these artifacts. The proposed filter uses a regularization term to ensure that the pattern of the filtered signal is similar to that of respiration. It also ensures that the amplitude of the filter output is within the expected range of the IP signal by imposing an epsilon-tube on the filtered signal. The adaptive epsilon-tube filter is 100 times faster than the previously proposed nonadaptive version and achieves higher accuracies. Moreover, the experimental results, using several different performance measures, suggest that the proposed method outperforms popular MA reduction methods such as normalized least mean squares (NLMS) and recursive least squares (RLS) as well as independent component analysis (ICA). When used to extract the respiratory rate, the adaptive epsilon-tube achieves a mean error of 1.27 breaths per minute (BPM) compared to 4.72 and 4.63 BPM for the NLMS and RLS filters, respectively. When compared to the ICA algorithm, the proposed filter has an error of 1.06 BPM compared to 3.47 BPM for ICA. The statistical analyses indicate that all of the reported performance improvements are significant. PMID- 26863682 TI - Resource-Aware Mobile-Based Health Monitoring. AB - Monitoring heart diseases often requires frequent measurements of electrocardiogram (ECG) signals at different periods of the day, and at different situations (e.g., traveling, and exercising). This can only be implemented using mobile devices in order to cope with mobility of patients under monitoring, thus supporting continuous monitoring practices. However, these devices are energy aware, have limited computing resources (e.g., CPU speed and memory), and might lose network connectivity, which makes it very challenging to maintain a continuity of the monitoring episode. In this paper, we propose a mobile monitoring solution to cope with these challenges by compromising on the fly resources availability, battery level, and network intermittence. In order to solve this problem, first we divide the whole process into several subtasks such that each subtask can be executed sequentially either in the server or in the mobile or in parallel in both devices. Then, we developed a mathematical model that considers all the constraints and finds a dynamic programing solution to obtain the best execution path (i.e., which substep should be done where). The solution guarantees an optimum execution time, while considering device battery availability, execution and transmission time, and network availability. We conducted a series of experiments to evaluate our proposed approach using some key monitoring tasks starting from preprocessing to classification and prediction. The results we have obtained proved that our approach gives the best (lowest) running time for any combination of factors including processing speed, input size, and network bandwidth. Compared to several greedy but nonoptimal solutions, the execution time of our approach was at least 10 times faster and consumed 90% less energy. PMID- 26863683 TI - An Open Architecture to Support Social and Health Services in a Smart TV Environment. AB - OBJECTIVE: To design, implement, and test a solution to provide social and health services for the elderly at home based on smart TV technologies and access to all services. METHODS: The architecture proposed is based on an open software platform and standard personal computing hardware. This provides great flexibility to develop new applications over the underlying infrastructure or to integrate new devices, for instance to monitor a broad range of vital signs in those cases where home monitoring is required. RESULTS: An actual system as a proof-of-concept was designed, implemented, and deployed. Applications range from social network clients to vital signs monitoring; from interactive TV contests to conventional online care applications such as medication reminders or telemedicine. CONCLUSION: In both cases, the results have been very positive, confirming the initial perception of the TV as a convenient, easy-to-use technology to provide social and health care. The TV set is a much more familiar computing interface for most senior users, and as a consequence, smart TVs become a most convenient solution for the design and implementation of applications and services targeted to this user group. SIGNIFICANCE: This proposal has been tested in real setting with 62 senior people at their homes. Users included both individuals with experience using computers and others reluctant to them. PMID- 26863684 TI - Can Cluster-Boosted Regression Improve Prediction of Death and Length of Stay in the ICU? AB - Sharing of personal health information is subject to multiple constraints, which may dissuade some organizations from sharing their data. Summarized deidentified data, such as that derived from k-means cluster analysis, is subject to far fewer privacy-related constraints. In this paper, we examine the extent to which analysis of clustered patient types can match predictions made by analyzing the entire dataset at once. After reviewing relevant literature, and explaining how data are summarized in each cluster of similar patients, we compare the results of predicting death, and length of stay (LOS) in the ICU1ICU: Intensive care unit. PMID- 26863685 TI - Biased Multiobjective Optimization and Decomposition Algorithm. AB - The bias feature is a major factor that makes a multiobjective optimization problem (MOP) difficult for multiobjective evolutionary algorithms (MOEAs). To deal with this problem feature, an algorithm should carefully balance between exploration and exploitation. The decomposition-based MOEA decomposes an MOP into a number of single objective subproblems and solves them in a collaborative manner. Single objective optimizers can be easily used in this algorithm framework. Covariance matrix adaptation evolution strategy (CMA-ES) has proven to be able to strike good balance between the exploration and the exploitation of search space. This paper proposes a scheme to use both differential evolution (DE) and covariance matrix adaptation in the MOEA based on decomposition. In this scheme, single objective optimization problems are clustered into several groups. To reduce the computational overhead, only one subproblem from each group is selected to optimize by CMA-ES while other subproblems are optimized by DE. When an evolution strategy procedure meets some stopping criteria, it will be reinitialized and used for solving another subproblem in the same group. A set of new multiobjective test problems with bias features are constructed in this paper. Extensive experimental studies show that our proposed algorithm is suitable for dealing with problems with biases. PMID- 26863686 TI - NMF-Based Image Quality Assessment Using Extreme Learning Machine. AB - Numerous state-of-the-art perceptual image quality assessment (IQA) algorithms share a common two-stage process: distortion description followed by distortion effects pooling. As for the first stage, the distortion descriptors or measurements are expected to be effective representatives of human visual variations, while the second stage should well express the relationship among quality descriptors and the perceptual visual quality. However, most of the existing quality descriptors (e.g., luminance, contrast, and gradient) do not seem to be consistent with human perception, and the effects pooling is often done in ad-hoc ways. In this paper, we propose a novel full-reference IQA metric. It applies non-negative matrix factorization (NMF) to measure image degradations by making use of the parts-based representation of NMF. On the other hand, a new machine learning technique [extreme learning machine (ELM)] is employed to address the limitations of the existing pooling techniques. Compared with neural networks and support vector regression, ELM can achieve higher learning accuracy with faster learning speed. Extensive experimental results demonstrate that the proposed metric has better performance and lower computational complexity in comparison with the relevant state-of-the-art approaches. PMID- 26863687 TI - Long-Term Air Pollution and Traffic Noise Exposures and Mild Cognitive Impairment in Older Adults: A Cross-Sectional Analysis of the Heinz Nixdorf Recall Study. AB - BACKGROUND: Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce. OBJECTIVES: We analyzed the cross sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI. METHODS: At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50-80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two exposure models. RESULTS: Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)]. CONCLUSIONS: Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype. CITATION: Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jockel KH, Moebus S, Hoffmann B, on behalf of the Heinz Nixdorf Recall study Investigative Group. 2016. Long-term air pollution and traffic noise exposures and mild cognitive impairment in older adults: a cross-sectional analysis of the Heinz Nixdorf Recall Study. Environ Health Perspect 124:1361-1368; http://dx.doi.org/10.1289/ehp.1509824. PMID- 26863689 TI - The Authors Reply. PMID- 26863688 TI - Associations of Residential Long-Term Air Pollution Exposures and Satellite Derived Greenness with Insulin Resistance in German Adolescents. AB - BACKGROUND: Epidemiological studies have identified associations between air pollution and green space access with type 2 diabetes in adults. However, it remains unclear to what extent associations with greenness are attributable to air pollution exposure. OBJECTIVES: We aimed to investigate associations between long-term exposure to air pollution and satellite-derived greenness with insulin resistance in adolescents. METHODS: A total of 837 participants of two German birth cohorts (LISAplus and GINIplus) were included in the analysis. Generalized additive models were used to determine the association of individual satellite derived greenness defined by the Normalized Difference Vegetation Index (NDVI), long-term air pollution exposure estimated by land-use regression (LUR) models with insulin resistance (HOMA-IR) in 15-year-old adolescents. Models were adjusted for study area, cohort, socioeconomic, and individual characteristics such as body mass index, physical activity, and smoking. RESULTS: Increases of 2 SDs in nitrogen dioxide (NO2; 8.9 MUg/m3) and particulate matter <= 10 MUm in diameter (PM10; 6.7 MUg/m3) were significantly associated with 11.4% (95% CI: 4.4, 18.9) and 11.4% (95% CI: 0.4, 23.7) higher HOMA-IR. A 2-SD increase in NDVI in a 1,000-m buffer (0.2 units) was significantly associated with a lower HOMA-IR (-7.4%; 95% CI: -13.3, -1.1). Associations tended to be stronger in adolescents who spent more time outside and in those with lower socioeconomic status. In combined models including both air pollution and greenness, only NO2 remained significantly associated with HOMA-IR, whereas effect estimates for all other exposures attenuated after adjustment for NO2. CONCLUSIONS: NO2, often considered as a marker of traffic, was independently associated with insulin resistance. The observed association between higher greenness exposure and lower HOMA-IR in adolescents might thus be attributable mainly to the lower co-exposure to traffic related air pollution. CITATION: Thiering E, Markevych I, Bruske I, Fuertes E, Kratzsch J, Sugiri D, Hoffmann B, von Berg A, Bauer CP, Koletzko S, Berdel D, Heinrich J. 2016. Associations of residential long-term air pollution exposures and satellite-derived greenness with insulin resistance in German adolescents. Environ Health Perspect 124:1291-1298; http://dx.doi.org/10.1289/ehp.1509967. PMID- 26863690 TI - Author response. PMID- 26863691 TI - In This Issue: Multilevel Effects. PMID- 26863692 TI - Preface. PMID- 26863693 TI - MANY PLAYERS ROIL THE RESEARCH WATERS. PMID- 26863695 TI - Looking For Signs Of Substance Abuse. PMID- 26863694 TI - STEPS TO STAFF STABILITY PART ONE: HELP WANTED! ACHIEVE STAFF STABILITY WITH GOOD HIRES AND WELCOMES. PMID- 26863696 TI - DOJ Initiative Targets Employees For Misconduct. PMID- 26863697 TI - OIG To Scrutinize Therapy Group Assignments. PMID- 26863698 TI - Got Resilience? PMID- 26863699 TI - Impact of Incivility in Nursing. PMID- 26863700 TI - Neuropathic Pain Management: A Reference for the Clinical Nurse. AB - The International Association for the Study of Pain neuropathic pain guidelines are presented. Nursing considerations, including neuropathic pain assessment and medication efficacy, are reported to explain medications' primary mechanisms of action and provide a nursing reference for patient education. PMID- 26863701 TI - How Well Do Inexpensive, Portable Pulse Oximeter Values Agree with Arterial Oxygenation Saturation in Acutely Ill Patients? AB - The purpose of this study was to examine the level of agreement between a portable SpO2 device and the clinical gold standard SaO2 in intermediate care patients. PMID- 26863702 TI - Nursing Surveillance and Physiological Signs of Deterioration. AB - A retrospective chart review was conducted to determine the impact of nursing surveillance on rapid deterioration. Data were collected on vital signs, recognition of mentation changes, and assessment of urinary output. Specific components of nursing surveillance that permit recognition of deteriorating patients remain unclear. PMID- 26863703 TI - Addressing Needs of Long-Term Care Facility Residents During Acute Hospitalization. AB - Patients who reside in long-term care facilities for extended periods of time offer many health care challenges. Recognition of early signs of illness, care transitions, and underutilization of community resources are common concerns. PMID- 26863704 TI - Maggot Debridement Therapy: Advancing to the Past in Wound Care. AB - Maggot debridement therapy (MDT) is experiencing resurgence as an effective alternative to conventional mechanical debridement in nonhealing wounds, especially those with antibiotic-resistant organisms. MDT has antibiotic, antifungal, and anti-inflammatory properties. Military use is on the rise. PMID- 26863705 TI - Pharmacotherapy of Type 2 Diabetes Mellitus: Navigating Current and New Therapies. AB - The keys to optimal glycemic control in patients with type 2 diabetes are early diagnosis and interventions that include lifestyle changes and pharmacotherapy. This review discusses therapeutic goals and current options for treatment of type 2 diabetes. PMID- 26863706 TI - Assessing Oral Hygiene in Hospitalized Older Veterans. AB - Poor oral health for all older adults can result in higher risk for heart disease, stroke, diabetes, and oral cancer. Findings from this study indicated older veterans needed to improve their oral hygiene habits but barriers to oral hygiene performance prevented them from receiving and performing oral hygiene measures. PMID- 26863707 TI - Unveiling the Truth about Nurses' Personal Preparedness for Disaster Response: A Pilot Study. AB - Although nurses are essential caregivers in disaster response, many are not prepared personally to report to the workplace during disaster situations. An online disaster preparedness education intervention to support personal readiness is described in this pilot study. PMID- 26863708 TI - A Critical-Thinking Acronym for Diabetes Care. PMID- 26863709 TI - CCCTM Exam: Validating the Expertise of Care Coordination and Transition Management. PMID- 26863710 TI - Research Questions and Hypotheses. PMID- 26863711 TI - Do You Suffer from Meeting Inflation?. PMID- 26863712 TI - Cytotoxic chemotherapy administration in the community: A case study. PMID- 26863713 TI - Workplace, culture--how safe is your practice when giving medications? PMID- 26863714 TI - A constructivist grounded theory study of mental health clinicians' boundary maintenance. AB - This study sought to understand how mental health clinicians (MHC) establish and maintain the professional boundary in their everyday practice. The findings indicate the establishment and maintenance of the professional boundary and the continual process of engaging the client are inextricably linked. Furthermore the use of interpersonal and professional skills are necessary to establish and maintain the professional boundary on an ongoing basis. A basic social process of engaging clients emerged from the analysis and indicated that a broader understanding of establishing and maintaining boundaries within the mental health context was warranted. PMID- 26863715 TI - Bullying, relational aggression and nursing. PMID- 26863716 TI - Why teachers are giving a Gonski. PMID- 26863717 TI - Improving community nursing care services through the academic nursing centre model. PMID- 26863718 TI - Resource packs to facilitate exercise on dialysis. PMID- 26863719 TI - RDNS and Bowls Australia team up to provide health education. PMID- 26863721 TI - Primary healthcare nursing workforce development. PMID- 26863720 TI - The health of Australian nomads. PMID- 26863722 TI - Weenthunga--helping future generations to make healthy decisions. PMID- 26863723 TI - Supporting individuals receiving chemotherapy in their home. PMID- 26863724 TI - Raising awareness of the corneal donation program. PMID- 26863725 TI - Coffee and conversation: Creation of a wound clinic. PMID- 26863726 TI - Applying psychosocial theories for nursing students. PMID- 26863728 TI - A study into suicide attempt aftercare. PMID- 26863727 TI - Hepatitis B antenatal care in the community. PMID- 26863730 TI - Answer. PMID- 26863729 TI - Achieving health equity for people with disabilities: a call to action. PMID- 26863731 TI - Oral and Maxillofacial Pathology. Case of the Month. Diagnosis. Pregnancy tumor (Pyogenic granuloma). PMID- 26863732 TI - CAT OF THE MONTH. Critically Appraised Topics. No Relationship Between Obstructive Sleep Apnea and Premolar Extraction (UT CAT #2917). PMID- 26863733 TI - Changes in Children's Oral Health Status and Receipt of Preventive Dental Visits, United States, 2003-2011/2012. AB - INTRODUCTION: Oral health represents the largest unmet health care need for children, and geographic variations in children's receipt of oral health services have been noted. However, children's oral health outcomes have not been systematically evaluated over time and across states. This study examined changes in parent-reported children's oral health status and receipt of preventive dental visits in 50 states and the District of Columbia. METHODS: We used data from the 2003 and the 2011/2012 National Survey of Children's Health. National and state level estimates of the adjusted prevalence of oral health status and preventive dental visits were calculated and changes over time examined. Multivariable logistic regression was used to compare outcomes across all states and the District of Columbia for each survey year. RESULTS: The percentage of parents who reported that their children had excellent or very good oral health increased from 67.7% in 2003 to 71.9% in 2011/2012. Parents who reported that their children had preventive dental visits increased from 71.5% in 2003 to 77.0% in 2011/2012. The prevalence of children with excellent or very good oral health status increased in 26 states, and the prevalence of children who received at least 1 preventive care dental visit increased in 45 states. In both years, there was more variation among states for preventive dental visits than for oral health status. CONCLUSIONS: State variation in oral health status and receipt of preventive dental services remained after adjusting for demographic characteristics. Understanding these differences is critical to addressing the most common chronic disease of childhood and achieving the oral health objectives of Healthy People 2020. PMID- 26863734 TI - 5 STRATEGIES FOR STIMULATING CASH FLOW IN 2016. PMID- 26863735 TI - [Structural Polymorphism of Genome Islands Encoding Resistance to Beta-Lactams in Coagulase-Negative Staphylococci Isolated at Hospitals of the Russian Federation]. AB - Coagulase-negative staphylococci (CoNS) are considered as a reservoir of mobile genetic elements and first of all of the staphylococcal cassette chromosome mec (SCCmec), defining staphylococci resistance to beta-lactams. Types II, IV, IVa, V, VII and VIII SCCmec were detected among 95 staphylococcal strains isolated in different regions of the Russian Federation. Subtypes C1a, C1b, C1c and C1 SCCmec were also identified (class B mec complex and two complexes of ccr1 and ccr2 genes recombinases). Some other cassette types carrying A, C1 and C2 classes of the mec complexes in combination with various recombinase genes were detected. The S.epidermidis isolates mainly formed cassettes carrying mec complex B, while the S. haemolyticus isolates had cassettes carrying classes C1 and C2 mec complex. Out of 9 isolates of S. hominis 5 isolates carried a new type cassette: class A mec complex in combination with the complex of the recombinase ccr1 genes. SCCmec was not identified in S. capitis and S. pasteuri. Their representatives carried either mec complex (1 isolate of S. pasteuri) or the recombinase complexes (2 isolates of S. capitis). The detected SCCmec variants in CoNS could be a source of emergence of new genetic lines of MRSA. PMID- 26863736 TI - [Investigation of Therapeutic Efficacy of Triazavirin Against Experimental Forest Spring Encephalitis on Albino Mice]. AB - The comparative study of the therapeutic efficacy of Triazavirin against experimental Forest-Spring encephalitis on albino mice vs. the active drug Ribavirin(r) showed that in high doses (200-400 mg/kg) Triazavirin moderately protected the infected animals. A significant increase of the animal lifespan in the test groups (from 4.1 to 4.8 days) and a statistically (p <= 0.05) valid decrease of the virus accumulation in the target organ (the brain) were observed. PMID- 26863737 TI - [Assessment of Antitumor Effect of Submerged Culture of Ophiocordyceps sinensis and Cordyceps militaris]. AB - Ophiocordyceps sinensis and Cordyceps militaris metabolites showed a high potential in the treatment of tumors as well as some other diseases. Antitumor properties of O. sinensis and C. militaris submerged mycelium were investigated. It was found that the O. sinensis dry biomass in a dose of 50 mg/kg administered once a day to the mice with subcutaneously inoculated P388 lympholeucosis lowered the tumor growth by 65% vs. 54% for the C. militaris dry biomass. The water extract of O. sinensis submerged culture however accelerated the growth of the P388 lympholeucosis tumor node in the mice almost two times, compared to the control. A greater caution in using this fungus as a source of biologically active substances is required since unwanted tumor-stimulating effects can arise. PMID- 26863738 TI - [Immunomodulator Intensification of Etioropic Therapy in Patients with Advanced Pulmonary Tuberculosis]. AB - The study was aimed at possible increase of the therapy efficacy in patients with advanced tuberculosis by including immunomodulators to the treatment schemes. The data concerning 6034 patients with advanced tuberculosis, mainly fibrocavernous tuberculosis of the lungs, were analysed. Four groups of the patients were randomized. In group 1 the management of the patients included etiotropic therapy and some treatment and rehabilitation measures with the use of Cycloferon. The group 2 patients in addition to the etiotropic therapy and some treatment and rehabilitation measures were given Omega-3. In group 3 the management included the etiotropic therapy and some treatment and rehabilitation measures. In group 4 the etioropic therapy was used alone. The analysis showed that 3419 patients had primary pulmonary tuberculosis, 340 patients had relapsing tuberculosis and 2275 patients had long-term process. The etiotropic therapy efficacy was estimated after an intensive phase of not more than 3 months. In the cases with Mycobacterium tuberculosis drug resistance and some other unfavourable factors it was estimated after a 5-month intensive phase. The results confirmed that inclusion of immunomodulators to the treatment schemes allowed to increase the therapy efficacy and the patients' adherence to the treatment, as well as to shorten the period of the bacteria carriage. Thus, the use of Cycloferon in the schemes of the treatment of the patients with fibrocavernous pulmonary tuberculosis allowed to shorten the period of the pathogen carriage (as well as the drug resistant forms) in 94.1 +/- 3.33% of the patients in spite of concomitant diseases. The effect of Cycloferon in such cases was likely due to both its direct immunoprotective action and the improvement of the general state of the patients and their higher adherence to the treatment. PMID- 26863739 TI - [Pharmacoeconomic Analysis of the Use of Hepatoprotectors in Management of Drug Associated Liver Injury Due to Hodgkin's Lymphoma Chemotherapy]. AB - The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use. PMID- 26863740 TI - [Selective Isolation of Rare Actinomycetes from Soil]. AB - Many diverse methods for selective isolation of actinomycetes are used in discovery of organisms producing biologically active substances, as well as in ecological studies. Methods for isolation of rare actinomycetes from soil are reviewed. PMID- 26863741 TI - [Methodology of Screening New Antibiotics: Present Status and Prospects]. AB - Due to extensive distribution of pathogen resistance to available pharmaceuticals and serious problems in the treatment of various infections and tumor diseases, the necessity of new antibiotics is urgent. The basic methodological approaches to chemical synthesis of antibiotics and screening of new antibiotics among natural products, mainly among microbial secondary metabolites, are considered in the review. Since the natural compounds are very much diverse, screening of such substances gives a good opportunity to discover antibiotics of various chemical structure and mechanism of action. Such an approach followed by chemical or biological transformation, is capable of providing the health care with new effective pharmaceuticals. The review is mainly concentrated on screening of natural products and methodological problems, such as: isolation of microbial producers from the habitats, cultivation of microorganisms producing appropriate substances, isolation and chemical characterization of microbial metabolites, identification of the biological activity of the metabolites. The main attention is paid to the problems of microbial secondary metabolism and design of new models for screening biologically active compounds. The last achievements in the field of antibiotics and most perspective approaches to future investigations are discussed. The main methodological approach to isolation and cultivation of the producers remains actual and needs constant improvement. The increase of the screening efficiency can be achieved by more rapid chemical identification of antibiotics and design of new screening models based on the biological activity detection. PMID- 26863743 TI - [Regulation of lymphocyte trafficking]. PMID- 26863742 TI - [Secondary Metabolites from Marine Microorganisms. I. Secondary Metabolites from Marine Actinomycetes]. AB - Review represents data on new active metabolites isolated from marine actinomycetes published in 2007 to 2014. Marine actinomycetes are an unlimited source of novel secondary metabolites with various biological activities. Among them there are antibiotics, anticancer compounds, inhibitors of biochemical processes. PMID- 26863744 TI - [Arrest peptides illuminate molecular autonomy in execution of the central dogma]. PMID- 26863745 TI - [Cell dynamics research using multi-color beetle luciferases]. PMID- 26863746 TI - [Structure and function of CRISPR-Cas9]. PMID- 26863747 TI - [Regulation of autoimmunity and tumor immunity by immunoinhibitory co-receptor, PD-1]. PMID- 26863748 TI - [Structure, dynamics and functions of the proteasome]. PMID- 26863749 TI - [Intravital fluorescence imaging by two-photon microscopy]. PMID- 26863750 TI - [Diversity of Mg2+ transporters involved in magnesium homeostasis]. PMID- 26863751 TI - [Regulation of lipid metabolism by miRNAs and transcription factors]. PMID- 26863752 TI - [Ribosome rescue systems in Escherichia coli]. PMID- 26863753 TI - [BRCA1-interacting protein OLA1 functions in the maintenance of genome integrity by centrosome regulation]. PMID- 26863754 TI - [Amelioration of neuronal injury by the expressional regulation of the glycosaminoglycan]. PMID- 26863755 TI - [Toward functional identification of functionally unknown proteins in nucleotide metabolism]. PMID- 26863756 TI - [Neutron Crystallography of the Complex Between Photosynthetic Pigment of Phycocyanobilin Synthesizing Enzyme and Substrate Biliverdin IXalpha]. PMID- 26863757 TI - [Regulation of proteostasis capacity in the mitochondria]. PMID- 26863758 TI - [Structures and functions of novel exopeptideses involved in peptide metabolism]. PMID- 26863759 TI - [The role of histamine-releasing factor in allergic inflammation]. PMID- 26863760 TI - [On the roles of NF-kappaB-inducing kinase in thymic T cell differentiation]. PMID- 26863761 TI - [Formation and regulation of electronegative molecules as an endogenous antigen]. PMID- 26863763 TI - [Cellular misfolded proteins transported to the cell surface by MHC class II molecules are targeted by autoantibodies]. PMID- 26863762 TI - [EMC is essential for biosynthesis of rhodopsin and other multipass membrane proteins in Drosophila photoreceptors]. PMID- 26863764 TI - [Quantitative analysis of lipids constructing plasma membrane microdomains by LC MS]. PMID- 26863765 TI - [DYNAMICS AND MECHANISMS OF INTERACTION OF HETERO-HEXAMERIC TIP49a/b COMPLEXES WITH DS-DNA]. AB - Evolutionary conserved TIP49a and TIP49b ATPases belong to the AAA+ superfamily of DNA-dependent ATPases that are involved in many cellular processes such as chromatin remodeling, regulation of transcription and cell division during mitosis, the maintenance of genome stability, snoRNP biogenesis, and participate in the formation of active form of telomerase. These proteins are involved in the complex networks of protein-protein interactions and, in spite of high structural similarity, in some cases, can perform opposite functions. Despite of the variety of their different activities, the exact mechanisms of action of TIP49a and TIP49b are still poorly understood. In this paper, by means of molecular docking approaches we first modeled the structures of hetero-hexameric TIP49 complexes with short ds-DNA fragments (20 base pairs with different GC content) within the central channel of hexameric ring. Using molecular dynamics simulations in the periodic water box (MD) we investigated conformational dynamics and mechanisms of DNA unwinding activity of these proteins. We shown that: a) the interaction between the positively charged protein loops and DNA within the central channel of protein ring leads to the partial unwinding of the DNA helix; b) DNA unwinding occurs only in the region within the protein ring, while the terminal parts of DNA outside the protein complex remain in its initial b-form conformation; c) the presence of ATP in the active sites of protein complex affects both the dynamics and the structure of DNA, leading to the breakage of some complementary bonds in AT-rich DNA sequences. PMID- 26863766 TI - [EXPRESSION OF THE LIGHT CHAINS OF IMMUNOGLOBULINS IN NORMAL B-CELLS AND SOME B CELL LYMPHOMAS]. AB - The quantitative method of determining the level of expression of immunoglobulin light chains on uncompensated data was suggested and used to examine disorders in light chain expression in various B-cell tumors. The average level of expression of the lambda isotype was 4 times higher than the level of expression of kappa isotype. The level of surface and cytoplasmic expression of LC IG varied within wide limits for different people, but there was a high degree of correlation between the levels of expression of kappa and lambda isotypes LC IG as well as between expression of the surface and cytoplasmic forms of each in isotype the same individual. In the majority of B-cell non-Hodgkin's lymphomas correlation between the expression of LC IG on the surface and in the cytoplasm of the cells was diminished. Expression of LC IG in CLL was significantly reduced on the surface of the cells and to a lesser extent--in the cytoplasm. In the case of marginal zone cell lymphoma, LC IG expression level was reduced on the surface of circulating cells and to a lesser extent--in the cytoplasm. In the case of mantle cell lymphoma and DLBCL, expression level of LC IG on the cell surface and in the cytoplasm was the same as in normal B-cells. However, in some cases DLBCL, no LC IG was expressed both on the surface and in the cytoplasm. PMID- 26863767 TI - [UROKINASE SYSTEM INVOLVES IN VASCULAR CELLS MIGRATION AND REGULATES THE GROWTH AND BRANCHING OF CAPILLARIES]. AB - Urokinase system representing urokinase-type plasminogen activator (urokinase, uPA) and urokinase re- ceptor (uPAR) plays an important regulatory role in the vascular wall and has the ability to run a proteolytic cascade, degradation of extracellular matrix and activate intracellular signaling in vascular cells. In this work, we have firstly shown a fundamental mechanism of urokinase system dependent regulation of the trajectory of growth and branching of blood vessels what may be of particular importance in the growth of blood vessels in early embryogenesis and in adults during the repair/regeneration of tissues. PMID- 26863768 TI - [OXIDATIVE STRESS-PROMOTED RESPONSES IN HUMAN ENDOMETRIAL STEM CELLS AND LUNG EMBRYONIC FIBROBLASTS]. AB - Human mesenchymal stem cells are an attractive cell source for tissue engineering. During transplantation they may be subjected to oxidative stress due to unfavorable cellular microenvironment, which is characterized by increased levels of reactive oxygen species. Recently, we have demonstrated that oxidative stress responses of human mesenchymal stem cells derived from endometrium (hMESCs) depend upon the oxidizer concentration. Besides, the duration of the H2O2-treatment duration. The effects of the high H2O2 doses on hMESCs and human lung embryonic fibroblasts were compared. In both cell types, H2O2-treatment for 60 min was shown to promote the multiphase cell cycle arrest, as well as to the dose-dependent cell death that occurred equally from all phases of cell cycle. However, the cell death dynamics in hMESCs and fibroblasts were different. Interestingly, in both cell types, shortening of H2O2-treatment duration from 60 to 10 min induced growth retardation, G1-phase accumulation and the cell size increase. Together, these findings allow us to suggest an induction of the premature senescence as a result of the short cell exposure to the high H2O2 doses. Thus, regarding both human endometrial stem cells and human embryonic fibroblasts, shortening of oxidative stress duration induced by high H2O2 doses enables to avoid the cell death and to produce the features of the premature senescence. PMID- 26863769 TI - [THE MODEL OF NEUROVASCULAR UNIT IN VITRO CONSISTING OF THREE CELLS TYPES]. AB - There are many ways to model blood brain barrier and neurovascular unit in vitro. All existing models have their disadvantages, advantages and some peculiarities of preparation and usage. We obtained the three-cells neurovascular unit model in vitro using progenitor cells isolated from the rat embryos brain (Wistar, 14-16 d). After withdrawal of the progenitor cells the neurospheres were cultured with subsequent differentiation into astrocytes and neurons. Endothelial cells were isolated from embryonic brain too. During the differentiation of progenitor cells the astrocytes monolayer formation occurs after 7-9 d, neurons monolayer--after 10-14 d, endothelial cells monolayer--after 7 d. Our protocol for simultaneous isolation and cultivation of neurons, astrocytes and endothelial cells reduces the time needed to obtain neurovascular unit model in vitro, consisting of three cells types and reduce the number of animals used. It is also important to note the cerebral origin of all cell types, which is also an advantage of our model in vitro. PMID- 26863770 TI - [ENTRY OF FACULTATIVE PATHOGEN SERRATIA GRIMESII INTO HELA CELLS. ELECTRON MICROSCOPIC ANALYSIS]. AB - Facultative pathogens Serratia grimesii are able to invade eukaryotic cells where they have been found in vacuoles and free in the cytoplasm (Efremova et al., 2001; Bozhokina et al., 2011). However, efficiency of this invasion is low, and the mechanisms of the invasion related to the initial steps of the process are not known. In the present study, we have increased the invasion efficiency by incubation of HeLa cells with N-acetylcysteine (NAC) preceding the infection. In the NAC-pretreated cells, two modes of S. grimesii to enter HeLa cells were observed. In the most cases, the penetration of S. grimesii into the cell was consistent with the "zipper mechanism", involving specific interaction of bacterial invasin with a host cell surface receptor. However, in some cases, bacteria were trapped by membrane ruffling probably produced by injected bacterial proteins that trigger the bacterial uptake process, as described in the "trigger mechanism". Further elucidation of bacterial and cellular factors involved in the bacteria-host cell interaction should clarify whether two different mechanisms or a predominant one operate during S. grimesii invasion. PMID- 26863771 TI - [PLASMALEMMAL ION TRANSPORT IN POLLEN TUBES IS REGULATED BY HYDROGEN PEROXIDE]. AB - Pollen tube growth is a key step in the life cycle of seed plants, which defines the success of sexual reproduction. One of the most important contributions to this process is made by ion transport through plasmalemma, which is tightly coordinated in time and space. Different classes of signaling molecules are involved in the regulation of transmembrane ion transport including reactive oxygen species as it has been recently demonstrated. Here, using subprotoplasts isolated from pollen tubes, we have demonstrated a connection between hydrogen peroxide, on one side, and two groups of targets on the plasma membrane, on the other side: nifedipine-sensitive Ca(2+)-permeable channels and transport systems controlling membrane potential. H2O2 interaction with these targets causes the increase in cytoplasmic Ca2+ concentration and plasmalemma hyperpolarization. One of the consequences of target modification was acceleration of cell wall regeneration. PMID- 26863772 TI - [EFFECT OF FUCOIDANS ISOLATED FROM SEAWEEDS LAMINARIA DIGITATA AND FUCUS VESICULOSUS ON CELL LINES HELA G-63, ECV 304 AND PC 12]. AB - The aim of the research was to investigate cytotoxicity of fucoidans on mammals cells. Three different samples of fucoidans were isolated from mechanically grounded brown algae Laminaria digitata and Fucus ve- siculosus. The sample F2 that differed from the others by higher sulfatation level and suppression of HeLa G-63 line culture growth was taken for further study in cell lines HeLa G-63, ECV 304 and PC 12. We have shown that fucoidan preparation F2 inhibits proliferation and induces cell death in a dose- and time-dependent manner for all investigated cell lines. Neuroendocrine tumor rat cell line PC 12 appeared to be the most sensitive to fucoidan treatment whereas endothelial human cells ECV 304 were the least sensitive. PMID- 26863774 TI - [A DEVICE FOR THE VACUUM TREATMENT OF HISTOLOGICAL MATERIAL]. AB - A device to carry out all types of vacuum infiltration in a wide temperature range. The device is easy to use and allows you to simultaneously conduct the infiltration of a large number of tissue samples. The main element of the device is a temperature-controlled cuvette, the temperature of which is set in the range of 23-65 degrees C. The design of the cell allows pumping air from the cell to the 50-100 mm Hg. In practice, histological methods are used to remove the vacuum infiltration of air from the tissue fixation (plant tissue), to accelerate the penetration of fasteners into the tissue. To carry out such a procedure, syringes, water pump and other hand-held devicesare used. Only vacuum infiltration allows a fill lyophilized tissue in paraffin. Efficiency of the described device is checked during the experiments at various fixing plant tissue and nervous tissue filling lyophilized in paraffin. PMID- 26863773 TI - [MORPHOLOGICAL FEATURES OF NEUTROPHILS AND EOSINOPHILS GRANULES IN SAPPHIRE MINKS]. AB - It has been established that sapphire minks have abnormality of subcellular structure of blood and bone marrow neutrophils and eosinophils. The abnormality consists in forming of abnormal "giant" granules. The si- ze and the number of abnormal granules significantly change during maturation of leucocytes in bone marrow. We have found differences between abnormal granules forming in neutrophils and eosinophils that depend on the maturing stage and the cells life cycle duration as well as morphofunctional features of these granulocytes. PMID- 26863775 TI - [Chronic Radiation Syndrome Among the Population of the Techa River Basin]. AB - Presented in the article is the analysis of the cases of the chronic radiation syndrome (CRS) diagnosed among members of the population exposed for multiple years to radiation due to radioactive contamination of the Techa River. The results of the more than 60-year period of observations have allowed us to assess not only the clinical manifestations of CRS during the period of its formation, but also the efficiency of the restoration processes going on in the human body after chronic radiation exposure, as well as its remote effects. The article discusses the problems of CRS diagnostics and especially its course in the cases of a combined (internal and external) radiation exposure when the red bone marrow becomes a critical organ. The analysis of CRS cases in dynamics for the exposed population characterized by a significant heterogeneity in terms of age, the initial health status and other factors modifying the person's radiosensitivity, allows us to regard the initial stage of CRS as a stereotypic dysregulating pathology. PMID- 26863776 TI - [Medical and Dosimetric Register of the Siberian Group of Chemical Enterprises Personnel--the Basis for the Evaluation of Chronic, Radiation Exposure Effects]. AB - The characteristic of medical and dosimetric register database of Siberian Group of Chemical Enterprises personnel is represented. This characteristic includes the description of the database structure, main sources of information, quantitative composition of the cohort under study, methods of evaluation of the external and internal irradiation doses, modern data on cancer incidence and reasons of death. The database is the basis for estimating the risk of the cancer and non-cancer effects after a long-term radiation exposure and dependence of "dose-response" at different levels: from population and group to cell and molecular. Now the database of register contains the information about more than 66,500 employees at the Siberian Group of Chemical Enterprises, about 22,000 of whom were exposed to external irradiation and more than 7500 employees--to internal irradiation. The register is the information resource of a large biological material bank. Using this bank, the research of chronic radiation exposure genetic effects and markers of individual radio sensitivity is performed. PMID- 26863777 TI - [Retrospective Cytogenetic Dose Evaluation. II. Computer Data Processing in Persons Irradiated in Different Radiation Accidents]. AB - The method for retrospective dose assessment based on the analysis of cell distribution by the number of dicentrics and unstable aberrations using a special computer program was earlier developed based on the data about the persons irradiated as a result of the accident at the Chernobyl nuclear power plant. This method was applied for the same purpose for data processing of repeated cytogenetic studies of the patients exposed to gamma-, gamma-beta- or gamma neutron radiation in various situations. As a whole, this group was followed up in more distant periods (17-50 years) after exposure than Chernobyl patients (up to 25 years). The use for retrospective dose assessment of the multiple regression equations obtained for the Chernobyl cohort showed that the equation, which includes computer recovered estimate of the dose and the time elapsed after irradiation, was generally unsatisfactory (r = 0.069 at p = 0.599). Similar equations with recovered estimate of the dose and frequency of abnormal chromosomes in a distant period or with all three parameters as variables gave better results (r = 0.686 at p = 0.000000001 and r = 0.542 at p = 0.000008, respectively). PMID- 26863778 TI - [The Changes of Properties of Blood Peripheral Lymphocytes of Donors and Patients with Prostate Gland Cancer: Reaction of Lymphocytes on Irradiation in vitro]. AB - The oxidative status (ROS), markers activation expression (CD69), proliferation activity (Ki67), proapoptotic antigen (CD95) have been investigated on healthy donors and patients with prostatic gland cancer in human blood lymphocytes. The lymphocyte reaction in vitro on gamma-irradiation at different doses (0.05-1.0 Gy) has been determined too. It was shown that in these two types of individuals the ROS content does not differ and the reaction on irradiation is not different either. Essential is the difference between the marker expression in lymphocytes of healthy donors and patients with tumour: in individuals with cancer the content of lymphocytes with CD69+ phenotype (in non active situation) and CD95+ increases, the expression of marker Ki67 decreases. The lymphocyte response to irradiation in healthy and tumour lymphocytes is distinguished. Irradiation at doses 0.05-10.0 Gy on tumour patients lymphocytes markers does not influence expression. In healthy donors' lymphocytes the expression of markers is changed considerably, the reaction depends on the marker type: expression of CD69 marker decreases (tendency); expression of Ki67 decreases too; it is unusual that the expression of CD95 changes--it decreases after irradiation at the doses of 0.05 1.0 Gy, then increases with dose. So this work shows the changes in tumour patients' blood lymphocytes in comparison with healthy donors' lymphocytes. The possible mechanisms of the observed phenomenon are discussed. PMID- 26863779 TI - [Release of Extracellular DNA after Administration of Radioprotective Combination of alpha-Tocopherol and Ascorbic Acid]. AB - Radioprotective and apoptotic activities of alpha-tocopherol acetate (vitamin E) and ascorbic acid (vitamin C) have been studied in 180 Wistar male rats. Rats were administered a single oral dose with vitamin E, vitamin C or their combination at prophylactic doses before or after the single whole body exposure to irradiation at the doses of 2 or 8 Gy. The radioprotective effect was evaluated by the frequency of chromosomal aberrations at metaphase plates of the bone marrow cells, apoptotic--by the level of circulating low-molecular-weight DNA (ImwDNA) in the blood plasma of irradiated rats. Administration of the combination of vitamins E and C before and after the irradiation at the dose of 2 Gy reduced the number of the cells with chromosomal aberrations thus providing the radioprotective effect, but separately administration of these vitamins did not show the significant radioprotective activity. Administration of the combination of vitamins E and C before irradiation with 8 Gy increased the lmwDNA in blood thus providing the apoptotic effect. So, synergy of radioprotective activities has been revealed in vitamins E and C action at prophylactic doses. Radioprotective effect of the combination of vitamins E and C can be associated with the apoptotic activity and can be explained by elimination of the least viable irradiated cells from the cell population. PMID- 26863780 TI - [Experimental Evaluation of Radioprotective Efficacy of Synthetic Genistein on Criteria of Glutathione System and Lipid Peroxidation in Erythrocytes of Peripheral Blood in Irradiated Rats]. AB - The study was aimed to evaluate experimentally the radioprotective effectiveness of synthetic genistein in terms of the glutathione system and lipid peroxidation in erythrocytes of irradiated rats. The animals were exposed to single acute X ray irradiation at a dose of 6 Gy. Genistein was administered intraperitoneally at 200 mg/kg 1 hour before radiation exposure. The irradiation caused the initiation of lipid peroxidation in the background depletion of reduced glutathione. Decrease by 25% in the number of malondialdehyde in the rats treated with genistein was registered 5 min after irradiation compared with the control. It is established thatl day after irradiation the level of reduced glutathione in the rats treated with genistein was 26% higher. However, intraperitoneal administration of genistein did not cause statistically significant changes in the activity of glutathione reductase, glutathione-S-transferase, or glucose-6 phosphate dehydrogenase during the whole period of observation. The results suggest that the radioprotective effect of synthetic genistein is implemented, along with other mechanisms, by stimulating the glutathione system and reducing the severity of lipid peroxidation. PMID- 26863781 TI - [Blood DNA Radiosensitivity May Be Predictive Marker for Efficacy of Radiation Therapy in Glioma Tumorbearing Individuals]. AB - Animal and clinical studies were conducted to evaluate the association between the blood DNA radiosensitivity, assessed by determining the original S-index ex vivo, and the response of gliomas to irradiation in vivo. Possible modifications of the latter after administration of iron-containing water (ICW) in rats were also explored. The study was performed on the rats with subcutaneously implanted experimental glioma-35. The tumors were locally X-irradiated with a single 15 Gy dose as a radiation therapy (RT). ICW (60-63 mg . Fe 2+/l) was administered as a drinking water for 3 days before treatment. The animals underwent blood sampling for analysis of the DNA concentration and leukocyte count. The DNA index was estimated 24 h after RT. The S-index was evaluated within 4 h before RT. The mean initial S-index in the blood samples of glioma-bearing rats was 0.73 +/- 0.05. Addition of ICW ex vivo resulted in a significantly increased S-index in a half of the samples. In general, the irradiated rats, which had been given pretreatment with ICW and demonstrated an ex vivo increase of the S-index to > 1.0, showed the most marked inhibition of tumor progression and the smallest tumor volume 25 days after irradiation. They also exhibited the lowest rate of growth and the longest survival. Determination of the biochemical S-index and evaluation of its changes ex vivo caused by ICW may be predictive of the response of experimental glioma to irradiation with radiomodification. The S-index may serve as a predictive indicator in clinic of the efficient evaluation of RT in patients with glioma. PMID- 26863782 TI - [Early and Delayed Effects of Radio Frequency Electromagnetic Fields on the Reproductive Function and Functional Status of the Offspring of Experimental Animals]. AB - The aim of our experimental research was to study the impact of radio frequency electromagnetic fields (RF EMF) on the reproductive function of male and female mice of CBA in 2 models of exposure, as well as on the morphofunctional state of progeny of irradiated animals. It was found that RF EMF under conditions of repeated short-term exposures (within 5 days for 10 minutes at PES 1.2 mW/cm2) affects the course of pregnancy in female mice, the number of litters, fertility and preservation of offspring, morphometric characteristics of the offspring of experimental animals at different models of irradiation (exposure of animals to RF EMF prior to mating and during pregnancy). PMID- 26863783 TI - [About Dose-Effect Relationship in the Environment Radiation Protection]. AB - One of the most important stages in the development of a methodology for the environment radiation protection is the assessment and justification of critical radiation exposure levels for ecosystem components. In this study application of the approach for critical dose level estimation is demonstrated on the example of the data about ionizing radiation effect on reproduction and survival of agricultural plants after acute and chronic exposures. Influence of the type of dose-effect relationship on the estimated values of the critical doses and dose rates is studied using three models (linear, logarithmic and logistic). The findings obtained do not provide any robust recommendations in favor of one of the three tested functions. The models of dose-effect relationship (threshold or non-threshold) and types of radiation-induced effects (stochastic and deterministic) are discussed from the viewpoint of developing a system for radiation protection of human and non-human biota. PMID- 26863784 TI - [Specific Features of Scots Pine Seeds Formation in the Remote Period after the Chernobyl NPP Accident]. AB - The results of long-term (2007-2011) observations on the quality of seed progeny in Scots pine populations inhabiting the sites within the Bryansk region contaminated as a result of the Chernobyl NPP accident are presented. Formed under the chronic exposure seeds are characterized by a high interannual variability, which is largely determined by weather conditions. PMID- 26863785 TI - [The 62nd Session of the United Nations Scientific Committee on the Effects of Atomic Radiation]. PMID- 26863786 TI - [Russian Scientific Conference with International Participation "Medical and Biological Problems of Toxicology and Radiobiology" (4-6 June 2015, St. Petersburg)]. PMID- 26863787 TI - [On the 60th Birth Anniversary of Sergey Viktorovich Fesenko]. PMID- 26863788 TI - [EPIDEMIOLOGICAL, CLINICAL AND MICROBIOLOGICAL FINDINGS IN WOMEN WITH AEROBIC VAGINITIS]. AB - Aerobic vaginitis (AV) is an alterarion of the normal lactobacillic flora accompanied by signs of inflammation, presence of mainly aerobic microorganisms from intestinal commensals or other aerobic pathogens. Clinical symptoms may vary by type and intensity and are marked by a high tendency for recurrence and chronification. Inflammation and ulcerations in AV could increase the risk of contracting HIV or other sexually transmitted infections. The aim is to study some epidemiological, clinical and microbiological features of the aerobic vaginitis in patients of the specialized Obstetric and Gynecological Clinic in Plovdiv, Bulgaria. In a retrospective research 4687 vaginal smears have been gathered in Microbiological laboratory at "St. George" Hospital - Plovdiv. We used clinical, microbiological and statistical methods. Information processing is performed by variation, alternative, correlation and graphical analysis using specialized package SPSS v13.0. The overall prevalence rate of AV in the studied population is 11.77%. The levels of prevalence of AV in pregnant and non-pregnant women are respectively 13.08% and 4.34%. The highest frequency of AV is in the age group 21-30 years (32.3%). The results show a marked association between Escherichia coli and the cases of AV (p < 0.001). AV is a common cause of vaginal symptoms in patients of specialized ambulatory outpatient. One in ten women with vaginal complaints suffers from AV Streptococcus agalactiae and Escherichia coli are most often isolated aerobic microorganisms. PMID- 26863789 TI - [COLPOSCOPY ASSISTED LASER MICROSURGERY FOR CERVICAL PATHOLOGY]. AB - AIM: A short presentation of the method--laser microsurgery and analysis of the achieved results. MATERIALS AND METHODS: 631 laser procedures were done for 3 years (2008- 2011) at Tokuda hospital outpatient department. These procedures were divided as follows: 607 laser vaporizations and 24 laser conisations. Indications for vaporizations were: CINI-114 patients, CIN II--26 patients, CIN III (without invasion of the cervical os) -26 patients and 422 patients were done laser vaporization for different reasons-papiloma, leucoplakia, atypical vessels and so on.... Indications for laser conisations were: CIN I- 2 patients, CIN II- 2 patients, CIN III- 12 patients (all dysplasies entered the cervical os). After laser conisation, we take a sample of the cutting line in cervical channel, which in fact substitutes the curettage of the last one during standard cold knife conisation. Technically the laser procedures were done by CO2 laser LUMENIS, directed by, mounted on binocular colposcop Karl Zeiss and standard gas evacuation system, assembled with vaginal speculum. All patient were followed up for the period of 1 year-colposcopic exam and cytology (PAP smear). All procedures were recorded and the data base that is included in these records are: diagnosis, colposcopic picture and type of laser procedure. RESULTS: The follow up of 422 patients that underwent laser vaporizations for minor lesions show no complications and recidiv. Out of 185 patients vaporazied for CIN I- CIN III, only in one was found cervical dysplasia entering the CC during the follow up, which made it necessary to go for laser conisation (no further problems detected after it). 2 out of 24 laser conisations went under LHT because of dysplasia in the cutting edge (these patients were with finished reproduction plans) and one patient went for laser re-conisation(has no children)for the same reason. COMPLICATIONS: In 2 patients there was a heavy bleeding, which started within 6 hours after the procedure. Laser coagulation was done, vaginal tamponade was placed for 24 hours and there was no bleeding after their removal. CONCLUSIONS: The results that we achieved with laser microsurgery, as also the results from other European centers allows us to recommend the laser vaporization/conisation as a save and sure method for the treatment of cervical dysplasias. PMID- 26863790 TI - [GLYCYRRHIZINIC ACID--AN ALTERNATIVE METHOD FOR TREATMENT OF CONDYLOMATA ACUMINATA]. AB - Condylomata acuminata are benign proliferations of skin and mucosa caused by the human papilloma virus infection (hereinafter referredto as HPV). It is one of the most common sexually transmitted diseases in the world, whose incidence rate has increased in the last three decades. Current treatment involves the physical destruction of the infected cells. The fact that there are many different types of treatment goes to show that none of them are uniformly effective or directly antiviral. PMID- 26863791 TI - [Pelvic exenteration--our experience]. AB - Pelvic exenteration is an operative method for one-moment removal of pelvic organs, including reproductive tract, bladder and rectosidgmoid. It most common indicated in gynecologic oncology for treatment of locally advanced cancer or recidive with central location. Pelvic exenteration can be used for healing of patients with genital cancer. Frequency of serious complications can reach 50%, that emphasizes the need of careful discuss of risks and benefits with the patients who are indicated for that kind of operation. For the period 2004-2012 common 46 exenterations are performed at FSHOG "St. Sofia", form which 9 are total (TE), 14 anterior (AE), 7 posterior (PE), 16 modified posterior exenterations (MPE). Average operative time is 459 min (237-620 min), depending on the type of operation. Average blood loss is 1200 ml (800-2500 ml). Report of the complications shows that eight patients have had 1-st degree complication. PMID- 26863793 TI - [THE GESTATIONAL DIABETES MELLITUS AS A SPECIFIC PREGNANCY STATE]. AB - Pregnancy is a condition which result in a significant changes in the course of the metabolic processes in woman's body. The impairments in the carbohydrate metabolism, in particular Gestational Diabetes mellitus are the most frequent observed during pregnancy. Extremely important for the clinician is to knows the risk factors, which can predispose to the appearance of these disorders, and in time to explores the patients. This allows to avoid both early and late complications for the mother and her future child. PMID- 26863792 TI - [ASSOSSIATION BETWEEN UNEMPLOYMENT, HEAVY PHYSICAL WORK AND PREMATURITY: RESULTS OF CASE-CONTROL STUDY IN PLEVEN]. AB - INTRODUCTION: Many studies confirmed the lower risk of prematurity among working women and established a link between heavy physical work and the prematurity. The aim of the study is to establish the association between unemployment and the heavy physical work of the mother during pregnancy and the birth of a premature baby. MATERIAL AND METHODS: In 2011 case-control study of two groups of premature (58) and mature (192) children born in 2007 in the University Hospital "George Stransky"-Pleven was conducted. For the aim of the study documentary method and sociological interview were used. The survey data were processed with statistical software packages. The significance of the results, findings and conclusions determined at p < 0.05. Odds ratio (OR) was used for assessment the strength of the association. RESULTS: In this study we found: more than four times higher risk of giving birth to a premature baby for unemployed mothers (OR = 4.48; 95% CI = 2.56-7.83; P = 0.01); more than two times higher risk of premature child birth among mothers performing heavy physical work during pregnancy (OR = 2.40; 95% CI = 1.03-6.19; P = 0.050) and the protective effect of having a job during pregnancy in association to the birth of a premature baby (OR = 0.26; 95% CI = 0.15-0.45; P = 0.001). CONCLUSION: We confirm our hypothesis that the unemployment and the heavy physical work during pregnancy increase the risk for birth of a premature baby. PMID- 26863794 TI - [OBESITY AND ENDOMETRIAL CARCINOGENESIS]. AB - Endometrial cancer is one of the main cancers occurring in industrialized countries. According to the National Cancer Registry in Bulgaria, cancer of the uterine body occupies 8.6% from all cancers in women and ranks second in frequency. It is found that over weight and obesity are a major risk factor for the development of endometrial cancer and the mortality associated with it. Adipose tissue is seen as endocrine organ, synthesizing so called adipocytokine - leptin, adiponectin, vistafin, that play a key role in the carcinogenesis of endometrial cancer and can be used as new markers for establishing the potential risk of this disease. The link between obesity, insulin resistance and endometrial cancer that has been proven, determines it as a socially significant disease. All this makes it necessary to clarify and specify the role of obesity in endometrial carcinogenesis and the development of strategies for the prevention and early diagnosis. PMID- 26863795 TI - [BRONCHOPULMONARY DYSPLASIA--WHAT DO WE KNOW TODAY?]. AB - The survival of great number of extremely premature newborn babies is associated with increased risk of damage of the newborn lung and development of chronic lung disease/Broncopulmonary dysplasia. The lower the gestational age and weight, the greater the frequency of BPD. The disease leads to impairment of the normal alveolization and vascularization of the premature lung. There are new theories for the pathogenesis of BPD and new staging of the disease. These changes lead to new therapeutic strategies. PMID- 26863796 TI - [CASE REPORT OF FETAL ASCITES CAUSED BY PRENATAL PERFORATION OF BOWEL]. AB - The detection of isolated ascites is a rare ultrasound finding. A precise examination should be undertaken in all cases fetal ascites. This include following a systematic protocol for diagnosis. The prognosis of the newborn in case of prenatal diagnosed ascites, depends on the etiology of the ascites. This is a case report of 40 years old pregnant women, at 34 weeks of gestation. During routine ultrasound examination at 33 weeks of gestation fetal ascites, has been diagnosed. The aim of our team was to examine the etiology of the ascites. We performed systematic diagnostic test and series of ultrasound examination, which helped us to diagnose fetal ascites, caused by bowel perforation. The good timing of delivery and postnatal surgical treatment were associated with good neonatal outcome. In cases of prenatal diagnosed ascites, the desirable good neonatal outcome requires multidisciplinary approach and team work of obstetric consultant, fetal medicine consultants, neonatologists and pediatric surgeons. However the parents should be counselled that not all of the associated anomalies could be diagnosed prenatally. PMID- 26863797 TI - [ACUTE ABDOMEN CAUSED BY COMPLICATED FIBROID IN PREGNANCY. CASE REPORT]. AB - With the advancing maternal age the rate of fibroids in pregnancy is also growing. A small part of fibroids in pregnancy are complicated and in about 2.6% necessitate urgent surgical treatment. We present a clinical case of subserose fibroid at 20 gestational weeks complicated with acute abdomen treated urgently with normal continuation of pregnancy. PMID- 26863798 TI - [TREATMENT OF EXTREMELY PREMATURE NEWBORN INFANT WITH INO. CLINICAL CASE]. AB - Prolonged inhaled nitric oxide (iNO) from birth in preterm neonates with BPD improves endogenous surfactant function as well as lung growth, angiogenesis, and alveologenesis. As a result there is a reduction in the frequency of the "new" form of BPD in neonates under 28 weeks of gestation and birth weight under 1000 gr. Delivery of inhaled nitric oxide is a new method of prevention of chronic lung disease. According to a large number of randomized trials iNO in premature neonates reduces pulmonary morbidity and leads to a reduction of the mortality in this population of patients. This new therapy does not have serious side effects. We represent a clinical case of extremely premature newborn infant with BPD treated with iNO. PMID- 26863799 TI - [OVARIAN ANASTOMOSING HEMANGIOMA WITH STROMAL LUTEINIZATION: A CASE REPORT]. AB - In 2009, Montgomery and Epstein coined the term "anastomosing hemangioma" for a newly described variant of capillary hemangioma with an unusual sinusoidal pattern, histologically mimicking angiosarcoma. The lesion was considered unique for genitourinary system with predilection to kidney but we found in the literature only 4 cases of this entity in ovaries. A 70-year-old woman presented with ultrasound visualized myometrial nodules and cystic formation of the right ovary, intraoperatively diagnosed as serous cystadenoma. Hysterectomy with bilateral adnexectomy was performed. The section of the ovary revealed a fortuitous finding in the cortex: circumscribed lesion, 7 mm in diameter, with mahogany brown, spongy appearance. Microscopic examination of H&E-stained slides manifested well-demarcated but un-encapsulated vascular proliferation, composed of tightly packed capillary-sized blood vessels with an anastomosing sinusoidal like architecture and tortuous "feeding" and "draining" vessels of medium caliber. Endothelial lining featured only mild cytologic atypia and lack of mitotic figures. The lesion was surrounded by luteinized ovarian stroma. Immunohistochemical examination with CD34 highlighted endothelial cells; SMA- supporting stromal cells. The anastomosing hemangioma of the ovary with stromal luteinisation was diagnosed as accidental finding. The authors discuss morphological characteristics of anastomosing hemangioma and the unusual for menopausal women but quite often combination between this lesion in the ovary and stromal luteinisation. PMID- 26863800 TI - [Protocol to induce abortion using Mifepristone and Misoprostol]. PMID- 26863801 TI - [L-carnitine: properties and perspectives for use in sports practice]. AB - The analysis of published data relating to the use in sports practice metabolic non-doping agent--L-carnitine. The review discusses some aspects of the mechanism of its action on the human body. The information is given about the role of carnitine in the energy processes, mechanisms of carnitine deficiency. On the basis of the literature is given scientific rationale for applying this metabolite in athletes, particularly with cardiovascular and immune disorders. PMID- 26863802 TI - [Effect of extrusion on the retention of amino acids and the nutritional value of the protein]. AB - The data of the literature on the impact factors of the extrusion cooking on physical and chemical properties of food proteins, biological value and digestibility have been discussed. Extrusion cooking is a high temperature short time process, characterizing by a minimal loss of nutrients. and biologically active substances compared to other methods of heat treatment of food. Studies of the properties of protein-containing products, protein isolates and concentrates in the extrusion are examined in different ways: the inactivation of antinutritional factors; improvement in digestibility and availability; changes in the content and chemical modification of amino acids; Maillard reactions involving amino acids; mutual enrichment of protein mixtures during the composite food extrusion; formation of functional technological properties of the extruded protein products. PMID- 26863803 TI - [Effects of rutin on protective capacity in rats]. AB - The purpose of the study was to determine effects of rutin dietary administration on the activity of xenobiotic-metabolizing enzymes and antioxidant status. The study has been carried out on 3 groups of male Wistar rats (n = 8 in each), with initial body weight 100-120 g. Animals of the control group (1st group) received standard semi-synthetic diet, the experimental groups--the same diet with rutin in the amount of 40 mg/kg b.w. (2nd group) or 400 mg/kg b.w. (3rd group). The duration of the experiment was 2 weeks. In rat liver the activity of quinone reductase (QR), heme oxygenase-1 (HO-1), paraoxonase-1 (PON-1), glutathione-S transferase (GST), ethoxyresorufin-O-dealkylase (EROD) activity of CYP1A1, methoxyresorufin-O-dealkylase (MROD) activity of CYP1A2, tes- tosterone 6beta hydroxylase (6beta-TG) activity of CYP3A, total antioxidant activity (AOA) and malondialdehyde (MDA) content have been investigated. The expression of genes CYP1A1, CYP1A2 and CYP3A has been measured by reverse transcription-polymerase chain reaction (RT-PCR). The stability of lysosome membranes was estimated by the change of unsedimentable activity of lysosomal enzymes--arylsulfatase, beta galactosidase and beta-glucuronidase. Rutin administration led to dose-dependent increase in the activity of antioxidant enzymes. In rats of the 3rd group received high-rutin diet the activity of QR, HO-1, PON-1 and GST increased by 68, 29, 17 and 22%, respectively, compared to the control (1st group); MDA level and AOA have not changed. Activity of EROD and MROD in liver microsomes of rats treated with rutin at a dose of 40 mg/kg b.w. (2nd group) increased by 33 and 58%, respectively, with a moderate increase in mRNA level of CYP1A1 and CYP1A2. Increasing the dose of rutin up to 400 mg/kg b.w. (3rd group) resulted in the decrease of the degree of EROD and MROD activation by 18 and 15%, respectively, compared to the 2nd group. Rutin had no significant effect on the activity of 6beta-TG and on the expression of CYP3A1 gene. Rutin dietary administration led to dose-dependent reduction of the unsedimentable activity of lysosomal enzymes, indicating the strengthening of the stability of lysosomal membranes. Thus, the obtained results showed that in healthy, intact rats high doses of rutin in the diet moderately but statistically significantly activate enzyme systems responsible for the protective and adaptive capacity of the organism. PMID- 26863804 TI - [Actual sanitary, epidemiological and hygienic aspects of a dietitian's activities in stationary medical institutions]. AB - The article shows the relevance of the main areas of dietitians' training to sanitary and epidemiological and hygienic issues of organization of clinical nutrition in stationary medical institutions (MIs) at training and refresher courses on dietetics. The attention is focused on the new legislative, policy and regulatory instruments, sanitary and epidemiological and hygienic requirements, providing high quality, safety and efficacy of nutritional therapy in MIs. The role of dietitian in the organization of clinical nutrition is highlighted. There were set out rights and responsibilities of a dietitian as a representative of MI under inspections by Rospotrebnadzor bodies; the demands, put forward by these bodies to the tested object, and actions, taken by them. PMID- 26863805 TI - [Lead toxicity in its joint administration with the aluminium oxide nanoparticles to rats]. AB - In this paper we studied the effect of aluminum oxide (Al2O3) nanoparticles (NPs) on the accumulation and biomarkers of toxic action of lead (Pb) when co administered to rats in subacute experiment. 36 Wistar rats with initial body weight 120-140 g were divided into 4 groups. Animal of group 1 (control group) were given distilled water by gavage. Rats in group 2 received Pb acetate solution in a dose of 20 mg/kg body weight (based on Pb), animal in the 3rd and 4th groups additionally to this received suspension of Al2O3 NPs in doses of 1 and 100 mg/kg body weight, respectively. The experiment lasted 22 days. Body and organ weight, standard haematologic parameters, protein, creatinine, uric acid level, aminotransferase activity (ALT and AST) in serum, urinary 5-aminolevulinic acid (5-ALA) concentration were measured. Apoptosis of hepatocytes was studied by flow cytometry. Pb content was determined by atomic absorption spectrometry. It has been shown that the administration of Al2O3 NPs together with Pb resulted in a significant dose-dependent increase in the relative weight of the kidneys (0.88 +/- 0.03% and 0.94 +/- 0.06% vs. 0.74 +/- 0.02% and 0.85 +/- 0.01% in control and group 1). The excretion of 5-ALA in the urine of animals treated with lead acetate significantly (p < 0.001) increased compared to the animals of group 1 (0.80 +/- 0.08/umol/l); while any dependence of this parameter on the dose of Al2O3 NPs was absent (p > 0.05) (group 2: 4.54 +/- 0.56 umol/l; group 3: 7.34 +/- 1.35 umol/l; group 4: 5.71 +/- 1.74 umol/l). The hemoglobin content was significantly reduced in animals of groups 2-4 (134.0 +/- 2.9; 133.6 +/- 1.8 and 129.9 +/- 2.9 g/l) compared to the animals of the control group (144.6 +/- 1.5 g/l), the dependence of this parameter on the dose of Al2O3 NPs was also absent. A marked and significant increase of the level of glucose has been noticed on the background of the Al2O3 and NPs (7.46 +/- 0.49 u 8.24 +/- 0.80 vs. 6.28 +/- 0.34 mmol/l in group 2), and its level went beyond physiological norms in the 4th group and ANOVA indicated the influence of Al2O3 NPs administration. The toxic effects of lead on hematological parameters of blood on the background of the Al2O3 and NPs weren't weakened, and in the case of hematocrit even enhanced, as evidenced by one-way analysis of variance (p < 0.05). When administered together with the Al2O3 Pd accumulated in increased amounts in the liver [up to 1.96 +/- 0.25 (group 3) and 2.16 +/- 0.23 (group 4) vs. 1.17 +/- 0.19 (group 2) mg/kg] (p < 0.05). Thus, Al2O3 NPs possibly presented as a contaminant in food can enhance the bioavailability of lead and some indices of its toxic action. PMID- 26863806 TI - [Gender and age characteristics and the trends in prevalence of obesity in the adult population in Russia during the 1994-2012 period]. AB - The analysis of the prevalence of overweight and obesity in adult age and sex groups of the Russian population in the dynamics of observation from 1994 to 2012 was based on anthropometric measurements of weight and height in Russian Longitudinal Monitoring Survey. The mean values of body mass index (BMI) and the frequency of obesity (BMI > 30.0) of the entire population have been increased during the observation period. The analyzing the data by gender revealed a significant increase in the frequency of obesity mainly among men, especially in the period 2005-2012, whereas among women increased incidence of obesity was negligible. The most rapid increase in the frequency of overweight and obesity in men noted in the age period of 20-30 years, and further increase in frequency of overweight and obesity with age were negligible. The rate of overweight and obesity in women had almost linear increase in the age period of 20-60 years. Comparative analysis of the prevalence of obesity showed that the obtained values for the 2000-2012 period were close to those characteristic of the developed world in recent decades. The growth of obesity rate in the general adult population in 2000-2005 and the 2005-2012 was 0.4% per year. At the same time, men showed a significant acceleration of the growth rate of obesity in the period 2005 to 2012 (0.61% per year) compared with the period 2000-2005 (0.44% per year). Increase in the frequency of obesity was observed in all regions in 2000 to 2012. The data should be considered as a rationale for research into the causes of gender differences in the prevalence of overweight and obesity in the first place to find differences in the peculiarities of dietary intake between men and women at different ages of life, leading to the development of overweight and obesity. PMID- 26863807 TI - [Monitoring the nutritional status of the residents of St. Petersburg]. AB - The purpose of the study was to analyze the diet of the population of St. Petersburg from different social and age groups and justify organizational methodological ways to improve it. 1200 inhabitants 18 years old and over (674 women, 526 men) were interviewed using questionnaires. One-third of St. Petersburg population did not adhere to the recommended 3-4 meals per day, taking meal 2 times per day or less (21.7%) or 5 times per day or more (11.3%). The young (18-29 years old) and socially active residents 1.5-2fold more likely than pensioners (13.8%) fed 2 times per day. Women 2.2 fold more frequently than men fed 5 times per day. Young people (20%) and socially active persons (24.4%) prefer not to have breakfast or take it 2-3 times per week compared with 9.6% pensioners. Supper as the main mealtimes called 27.8% women, that is 1.4 fold more likely than men. Thus, a great part of the population in the young and socially active adulthood violates proper diet, and women more often as compared to men. This can lead to disruption of the metabolic processes, increasing the risk of nutrition-related diseases, a decrease of efficiency and reduced life expectancy. This raises the feasibility of establishing of healthy eating offices based on health centers or clinics in St. Petersburg. PMID- 26863808 TI - [The content of selen in blood plasma in patients with acute Q-wave myocardial infarction]. AB - The level of blood plasma selenium was analyzed by microfluorimetric method in in patients and out-patients with acute coronary syndrome with ST-elevation resulting in acute Q-wave myocardial infarction. 72 patients, 40-75 years old, with acute Q-wave myocardial infarction were followed during a month. The initial decreased concentration of blood plasma selenium was recorded in most patients in the acute period of the myocardial infarction: deficiency of the microelement (< 90 mcg/l) was found in 30 subjects, the critical ranges (< 70 mcg/l) were stated in 33 patients. Just 2 patients had optimal concentration and 7 patients had a suboptimal one (90-114 mcg/l). Blood plasma level of the microelement increased in 2 weeks after myocardial infarction (in subacute stage) but it was still within deficient or critical levels. No difference was detected in selen concentration depending on gender, age, location on myocardial infarction, accompanying diseases, presence of some risk factors (smoking, alcohol abuse, hereditary predisposition to coronary artery disease). At the same time we revealed a significant Spearman rank correlation in patients with Q-wave myocardial infarction between basal level of blood serum selenium on the one hand, and electrocardiography indices (reflecting the rate of myocardial lesion and necrosis), echocardiography. data (which characterize myocardium reparation processes and remodeling), CPK (a prognostic marker of the myocardial necrosis), HDL-cholesterol (lipid profile index), blood potassium level and BMI on the other. PMID- 26863809 TI - [Sufficiency with water-soluble vitamins and state of bone in pregnant women]. AB - Vitamin status and bone strength have been estimated in 91 pregnant women (29.3 +/- 4.6 years old) from Moscow by non-invasive methods. Sufficiency with vitamins C, B2, B6 has been evaluated by morning urinary excretion of ascorbic acid, riboflavin and 4-piridoxic acid determined by visual titration and fluorimetric methods. The rate of bone resorption has been measured by the ratio of urinary calcium and creatinine, determined by complexometric titration and spectrophotometrically. The study of the bone strength has been conducted using an ultrasonic densitometer (the speed of the ultrasonic waves along the cortical layer). The lack of vitamin C was found in 20.4% .of the women surveyed, vitamin B2--in 27.4%. Vitamin B6 deficiency was detected most frequently (90%). Excretion of vitamins B2 and B6 in women in the third trimester of pregnancy was lower as compared with the women in the first and second trimester. In 53.3% of the women surveyed an increase in urinary excretion of calcium per creatinine has been observed. Excretion of group B vitamins (especially vitamin B6, 1.75 fold, p < 0.05) in women taking vitamin supplements was higher compared to non-taking vitamins that indicates the better sufficiency of the organism with these vitamins. Among women who took vitamin complexes, inadequate supply with water soluble vitamins C, B2 and B6 was detected less frequently (the difference was significant for vitamin B2) than among women who did not intake vitamin complexes (in 11.9, 27.7 and 42.4% vs 16.1, 54.8 and 48.8 %). The rate of bone resorption (Ca/creatinine) in women taking vitamins was smaller (0.19 +/- 0.09 vs 0.24 +/- 0.14, p > 0.05). Ca/creatinine ratio was within normal range in 40% of women who intake vitamins, while in women not taking vitamins--only in 22.2%; this value exceeded the upper limit of norm in the rest. The strength of bone was broken in women in the second and third trimester of pregnancy, having worse supply of vitamins. The percentage of agreement of the results of osteopenia diagnosis assessment (ultrasound densitometry and urinary Ca/creatinine) was 42.2%. Thus, the conclusion has been confirmed that the evaluation of the status of bone is possible only basing on the results of determination of several parameters. PMID- 26863810 TI - [Efficiency of application of the enriched bakery products in children nutrition]. AB - The results of the research devoted to an assessment of efficiency of application of the enriched bakery products in nutrition of school students have been presented. Composition and technology of the enriched bakery products have been developed. The influence of enrichers on the basis of proteins of whey, plasma of blood, hemoglobin, calcium and iodinated components and food fibers on the nutritive and energy value of bakery products has been defined. The consumption of 100 g of the enriched bakery products provides a significant amount of protein -12.5-23% of the recommended daily intake (RDI), to satisfy daily need of school students in calcium up to 13.4%, in iron--up to 20%, iodine--12.5% and food fibers--17.3%. When comparing blood hemoglobin content in school students after inclusion in a diet of the enriched bakery products, the lack of significant changes of this indicator in children with normal hemoglo- bin content has been determined that is the confirmation of safety of use of the products enriched with hem iron. At the same time, normalization of hemoglobin level in children (9.7%) with the initial threshold and lowered hemoglobin indicators is noted. The reliable increase in the content of hemoglobin in this group of children from 112 +/- 3 to 131 +/- 6 g/l was established (p <= 0.05). Positive dynamics of the content of iodine in urine at school students with initial deficiency of iodine under administration of the bread enriched with iodine has been defined. Ioduria indicators authentically increased from 88 +/- 10 to 116 +/- 9 mkg/l (p <= 0.05). Before diet correction in 53 from 59 children surveyed in the Stavropol region, a mild lack of iodine has been revealed (iodine levels less than 100 mkg/l urine), while after bread intake--only in 7 (11.9%) students. PMID- 26863811 TI - [Dynamics of elements distribution in blood, depending on age, by example of Moscow Region residents]. AB - Elemental status of a person determines the qualitative and quantitative content of chemical elements in the human body. This marker allows us to estimate the level of imbalance of chemical elements and therefore health risks. The method for simultaneous quantitative and qualitative analysis of 67 elements in biomaterials has been proposed. The detailed elemental analysis of whole blood samples of 1711 healthy people (age range 0-100 years) of Moscow Region has been performed. A number of patterns of age-related changes of the element status conditionally healthy people has been estimated. Na content in the samples increased with the age of the person. Presumably, this result reflects the studied populations nutrition disorders associated with immoderate consumption of table salt. The maximum content of Ca was observed in blood samples of people age range 0-20 years (66-69 mg/kg), the Ca content in the blood samples of people age range 26-85 years was significantly lower (59-62 mg/kg). The maximum decrease of Ca was detected in blood samples of people age range of 85-100 years (57-59 mg/kg). Thisreductionin the concentration of Ca, apparently due to age-related changes of Ca balance, correlates with decrease of bone mineral density and bone mass. Iron content decreased in the blood samples of people age range 10-100 years from 480 to 390 mg/kg. Selenium content in blood of people age range 0-25 years linearly increased, remained stable high in the blood of people age range 25-55 years (0,13-0,136 mg/kg) and then gradually decreased. A graph of As content dependence from a person's age is a mirror image of the graph of Se content dependence from a person's age, which is evidence of the antagonistic effects of these elements. Graphic changes in the content of rare earth elements Eu and Ho reflect the unidirectional trend of these elements accumulation. The maximum content of these elements was observed in blood samples of people age range of 25-65 years. Perhaps a reduction of Eu and Ho in the age range 65-100 years age reflects a downward trend in bone mineral density and decrease in bone mass, which correlates with the Ca content in the blood depending on the age of people. The data obtained showed a significant increase of U and V in the blood of people age range of 85-100 years. The compounds of vanadium and uranium normally relatively easily filtered by the kidneys and excreted in the urine. This result seems to demonstrate age-related deterioration in the functioning of the excretory system. A list of recommendations for nutrition correction of elemental imbalance of the observed population has been proposed. PMID- 26863812 TI - [Assessment of efficiency of use of the developed supplement containing selenium on laboratory animals]. AB - The article presents the results of a study of the effectiveness of wheat flour containing selenium in organic form. The organic form of trace element was achieved by transformation of selenium in selenium-methionine (Se-Met) at germination of wheat grains, moistened with a solution of sodium selenite. To determine the effectiveness of selenium- containing supplements experimental investigations were carried out on Long white rats with initial body weight 50 +/ 2 g. The duration of the experiment was 30 days. The research model included four groups of animals: control group--animals were fed a complete vivarium diet; group 1--a model of selenium deficiency, which was achieved by feeding selenium deficient food (grain growh in the Chita region of the Trans-Baikal Territory Zabaikalsky Krai); group 2--animals were administered selenium supplement in the form of enriched flour (0.025 ug Se per 50 g body weight of the animal) on the background of selenium-deficient diet; group 3--animals were treated with a high dose of selenium in the form of a solution of sodium selenite intragastrically through a tube (0.15 ug Se per 50 g body weight). Selenium-containing additive on the background of selenium-deficient diet had a positive impact on the appearance and behavior of animals, the body weight gain per head after 10 days in group 2 amounted to 47.9 g that was 4 fold larger than in rats of group 1. The study of selenium content showed that in the blood, liver, lungs and heart of rats treated with the additive on the background of selenium-deficient diet (group 2), selenium level did not differ from those in the control group and was within physiological norms. The experiment showed that selenium deficiency and rich in selenium rich diet has a significantly different effect on the studied parameters of oxidative-antioxidative status. The activity of blood glutathione peroxidase in animals of group 2 (did not differ from that in group 3) was almost 2 fold higher than in blood of control animals and was seven fold higher than that in blood of animals kept on selenium deficient diet (35.57 +/- 3.36 umol/g per 1 min) A similar dependence was established when studying the activity of glutathione reductase. It has been revealed thatthe oxidative-antioxidative status of animals from experimental groups 1 and 3 was lower than from control group and group 2. Thus, blood antioxidant activity in animals receiving diet with selenium deficiency and high dose of this trace element, was less than in the control group by 43.1 and 25.4%, respectively. Liver MDA level in animals kept on a diet with selenium deficiency exceeded the value of this indicator in the group 2 more than 1.5 fold (110.5 +/- 10.70 vs. 72.5 +/- 4.30 nmol/mg). When using selenium-containing supplement, this parameter decreased to the control level. In blood plasma of the animals of group 2 total antioxidant activity increased by about five times as compared with the indicators of animals kept on selenium-deficient diet, and was 25% higher than in control. Thus, the introduction of a selenium supplements in the deficient diet contributes to the development of endogenous antioxidants that suppress lipid oxidation. High biological effectiveness of supplements containing organic form of selenium has been proved. PMID- 26863813 TI - [Andrey Valerievich Vasil'ev]. PMID- 26863814 TI - [Minkail Magomed Gadzhievich Gapparov]. PMID- 26863815 TI - [Fracture strength of elastic and conventional fibre-reinforced composite intraradicular posts--an in vitro pilot study]. AB - OBJECTIVES: The purpose of this in vitro investigation was to evaluate the reinforcing effect of different fibre-reinforced composite (FRC) posts and insertion techniques in premolar teeth when using minimal invasive post space preparation. MATERIALS AND METHODS: Thirty two extracted and endodontically treated premolar teeth were used and divided into four groups (n = 8) depending on the post used (Group 1-4). 1: one single conventional post, 2: one main conventional and one collateral post, 3: one flexible post, 4: one main flexible and one collateral post. After cementation and core build-up the specimens were submitted to static fracture toughness test. Fracture thresholds and fracture patterns were recorded and evaluated. RESULTS: The multi-post techniques (group 2 and 4) showed statistically higher fracture resistance compared to group one. Regarding fracture patterns there was no statistically significant difference between the tested groups. CONCLUSION: The application of multiple posts seems to be beneficial regarding fracture resistance independent from the used FRC post. Fracture pattern was not influenced by the elasticity of the post. PMID- 26863816 TI - [The clinical application of zirconium-dioxide-ceramics. Case report]. AB - Due to its outstanding physical, mechanical and esthetic properties, zirconium dioxide is one of the most popular non-metal denture, capable of surpassing PFM in most cases. The recent advances of CAD/CAM technology makes it a good alternitve. Here we show the usefulness of zirconium-dioxide in everyday dental practice through three case reports. PMID- 26863817 TI - [Branchiogen cyst at unusual age and in rare localization. A case report]. AB - Branchiogen anomalies represent a heterogeneous group of developmental abnormalities, they arise from incomplete obliteration of branchial clefts and pouches during embriogenesis. Clinically they can present as a cyst, fistula or sinus. Second cleft lesions account for 95% of the branchial anomalies. Second branchial cleft cysts are usually located in the neck, along the anterior border of the stenocleidomastoid muscle, but they can be anywhere along the course of the second branchial fistula from the tonsillar fossa to the supraclavicular region. Their presence in the nasopharynx is extremely rare. Ultrasound, computed tomography (CT) or magnetic resonance imaging is recommended for diagnosis. Definitive treatment is surgical excision, these lesions do not regress spontaneously and often result recurrent infections. A 7 month old infant applied to a pediatrician with gastrointestinal viral infection. During examination a cystic mass was discovered in the right lateral nasopharyngeal wall, the lesion extended to the oropharynx. Marsupialisation was performed via transoral approach. In case of cystic lesion in the lateral epipharynx, branchial cleft cyst should be considered in the differential diagnosis. PMID- 26863818 TI - [Complete dental care of patients suffering from localized aggressive periodontitis. Case report]. AB - A 34 years old male patient was referred to our clinic for restorative dental treatment. During detailed consultation and dental examination a relatively rare form of periodontal disease had been diagnosed. Intraoral examination included recording of dental and periodontal status. Based on patient's dental history, measurements of probing pocket depths (PPD), clinical attachment level (CAL), and also the X-ray findings, Localized Aggressive Periodontitis (LAP) unknown by the patient was diagnosed. After patient's consent the comprehensive treatment plan covered the dental prevention, periodontal non-surgical and surgical therapy and rehabilitation. The treatment started with oral hygienic instruction, motivation then supra- and subgingival scaling and rootplaning. Later extraction and elective root canal treatment were performed, followed by open flap periodontal surgery combined with hemisection of two molars. After a full mouth conservative restorative therapy, function and esthetics were restored by fix dental prostheses. This case is a good example to underline the importance of periodontal examination during the dental screening and dental status recording for each patients showing up at dental clinics. Otherwise in many cases this asympthomatic disease can remain undetected. PMID- 26863819 TI - [Burning oral sensation: when is really BMS?]. AB - The aims and purposes of this systematic review of the international literature are to discuss and clarify some considerations on Burning Mouth Syndrome (BMS). Over the last 40 years, many researchers have addressed this disease clinically or experimentally. Thus, the etiology and pathogenesis of BMS remain unclear. We analyzed the etiopathogenesis of Burning Mouth Syndrome and of the burning oral sensation and currently, we could not find a consensus on the diagnosis and classification of BMS. Further studies are required to better understand the pathogenesis of BMS, and a "Gold Standard" classification is required because not every burning sensation in the mouth is BMS. PMID- 26863820 TI - Are We as Fat as We Can Get? PMID- 26863821 TI - Tobacco Use Trends among Mississippi Youth following the 1997 Settlement of Mississippi's Medicaid Lawsuit and Subsequent Tobacco Prevention Initiatives. AB - BACKGROUND: Mississippi has implemented several programs and policies to reduce youth tobacco. This study examines trends in youth tobacco use and compares current prevalence rates for cigarettes, cigars, smokeless tobacco, and e cigarettes. DESIGN/METHODS: The Youth Tobacco Survey is a self-administered survey of a multi-stage sample of public high school students. RESULTS: Cigarette and cigar smoking decreased from 1998 to 2014. However, current use of smokeless tobacco did not change and e-cigarette use has increased. Currently, there are no significant differences in the prevalence of cigarette, cigar, smokeless tobacco, or electronic cigarette use. CONCLUSION: The state has successfully decreased cigarette and cigar smoking. However, smokeless tobacco use has not changed and e cigarettes are becoming increasingly popular. Currently, Mississippi youth are at equal risk for cigarette, cigar, smokeless tobacco, or electronic cigarette use. Tobacco prevention efforts, clinician counseling, and policies should address each of these products rather than focus primarily on cigarettes. PMID- 26863822 TI - Is Vitamin D Deficiency Contributing to Mississippi's Persistent Black-White Disparity in Preterm Birth? PMID- 26863823 TI - My Immigration Story. PMID- 26863824 TI - MSMA PHYSICIAN Leadership ACADEMY Jonathan Jones, MD. PMID- 26863825 TI - Praise the Lord and Take Away their Ammunition! PMID- 26863826 TI - The Physician Abuse of Meaningful Use. PMID- 26863827 TI - Psychostimulants: Concerns over Long-Term Adverse Side Effects. AB - The personal rewards are substantial for the healthcare provider who can make teachers and parents happy. There are evolving, alternative methods of dealing with ADHD, but PS are relatively cheap and quick when they work (roughly 70% of the time) and readily accessible. We have no social or educational structures currently to deal with the extreme ADHD cases. In cases of less dramatic, attention problems, poor grades, where PS boost attention, physicians are unlikely to abandon their patients willingly, unless compelled to sacrifice short term goals over the unanswered questions about what is best in the long run. How can we know if it's the child and not the educational system that needs diagnosis and treatment? Psychiatric literature consistently suggests the prevalence of attention deficit in children is roughly 5% of the child population. Do 5% of our children need to take PS? This is where risks versus benefits enters the decision making process, and this is where this article aims to intentionally plant a healthy dose of scientific scrutiny. Ultimately, the doctor in charge makes a decision ... sometimes based on intangibles that cannot be legislated or defined by even the best scientific studies. It is not clear or scientifically established that the use of PS, especially in young, developing minds of children, is safe or meaningfully beneficial in the long run. There is much information in human and animal studies to question the wishful thinking that using mind altering drugs in children is the right thing to do. There are risks, and there are benefits. In this case, the risks are less obvious, cloaked in the inadequacy of our current state of knowledge, potentially threatening the quality of the lives we seek to enhance. PMID- 26863828 TI - Top Ten Facts You Need to Know About Clostridium difficile. PMID- 26863829 TI - A Rash Decision. PMID- 26863831 TI - E-CIGARETTES: In the News. PMID- 26863830 TI - FLUORIDE MYTHS DEBUNKED. PMID- 26863832 TI - Are we seeing an end to slow healthcare spending? PMID- 26863833 TI - Hospital cost-containment strategies that earn the respect of rating agencies. AB - To confirm that hospitals have the necessary structures and strategies in place to reduce costs and secure future market share, credit rating agencies analyze a variety of quantitative and qualitative criteria, including: Salaries and benefits, bad debt, age of plant and depreciation, and other line items that may point to inefficiencies in a hospital's expense structure. Cost-benefit analyses, strategic plans, and leadership qualities that show the long-term value of expense cuts, capital investments, and mergers and acquisitions. Cost-effective and clinically appropriate shifts in a hospital's outpatient-to-inpatient ratio. Liquidity and market share. PMID- 26863834 TI - Health care on demand: four telehealth priorities for 2016. AB - Consumers who are accustomed to on-demand, virtual services are looking for more convenient ways to access health care. Giving patients the opportunity to connect with physicians remotely can promote higher patient satisfaction and engagement. Telehealth options may have a high start-up cost, but that cost is likely well justified by the potential to enhance quality, outcomes, and customer attraction and satisfaction/retention over the long-term. PMID- 26863835 TI - Paving the way for Medicare reform. AB - Major changes set forth in the Medicare Access and CHIP Reauthorization Act are coming in 2019, but the time to prepare is now. The legislation includes three major changes: Pay-for-performance metrics. A two-track payment system. Consistent rate increases. PMID- 26863836 TI - Fast track to 340B. AB - Hospitals that are newly qualified for the 340B Drug Pricing Program may have an opportunity for fast-track approval to participate in the program. Three steps are required to seize this opportunity: Use data analytics to assess current and future percentages of Medicaid utilization and eligibility for federal SSI cash benefits. Determine the feasibility of early cost report filing. Prepare appropriate documentation and undertake the initial enrollment process. PMID- 26863837 TI - Integrating physical and behavioral health: a major step toward population health management. AB - Healthcare provider organizations have a choice of five basic approaches to integrating behavioral health services with primary care services, on a continuum from minimally integrated to fully integrated: Cultivation of improved communication and collaboration between the two disciplines. Establishment of primary care as the primary behavioral health caregiver. Co-location of primary care and behavioral health services. Integration of behavioral health with primary care only for chronic disease management. Total integration of primary care and behavioral health. PMID- 26863838 TI - Betting big on bundles. PMID- 26863839 TI - Harnessing the power of big data and data analysis to improve healthcare entities. PMID- 26863840 TI - Medicare claims data provide a perspective on trends in HAC rates. PMID- 26863841 TI - Send Me Your Doctor Stories. PMID- 26863842 TI - The Summer Food Service Program and the Ongoing Hunger Crisis in Mississippi. AB - Food insecurity is simply defined as uncertain access to adequate food. Nearly 50 million Americans, 16 million of whom are children, are food insecure. Mississippi has 21% food insecure citizens, and has the most food insecure county in the nation. Our state's school system's National Breakfast and Lunch Programs help combat food insecurity, but a gap still exists. This gap widens during the summer. In this paper, we describe the Mississippi Summer Food Service Program. While the program has had success in our state, it still faces challenges. Organized action by physicians in Mississippi and the Mississippi State Medical Association could significantly increase participation in these programs that are vital to our state. PMID- 26863844 TI - Top Ten Facts You Need to Know: About Abdominal Aortic Aneurysms. PMID- 26863843 TI - The Weak Kid. PMID- 26863845 TI - An Interview with Daniel P. Edney, MD 148th MSMA President, 2015-2016. PMID- 26863846 TI - Mississippi Children and Pragmatic Politics. PMID- 26863847 TI - Segregation Then, Poverty Now: Disparities Forever? PMID- 26863848 TI - SOUTH MISSISSIPPI CHARITY HOSPITAL, LAUREL, 1920. PMID- 26863849 TI - LIMITING OCCUPATIONAL MEDICAL EVALUATIONS UNDER THE AMERICANS WITH DISABILITIES ACT AND THE GENETIC INFORMATION NONDISCRIMINATION ACT. AB - Although medical care delivery by one's personal physician is the paradigmatic American healthcare arrangement, in the workplace setting, many Americans undergo medical evaluations to assess their fitness for duty or degree of impairment. This Article explores the complex and evolving legal status of occupational medical evaluations. Beginning with the legal and ethical frameworks of occupational medical practice, the Article then examines the effects of increasingly detailed legal regulation under the Americans with Disabilities Act and the Genetic Information Nondiscrimination Act on employees, employers, and physicians. PMID- 26863850 TI - RECONCEPTUALIZING CONSENT FOR DIRECT-TO-CONSUMER HEALTH SERVICES. AB - The market for direct-to-consumer (DTC) health services continues to grow rapidly with former patients converting to customers for the opportunity to purchase varied diagnostic tests without the involvement of their clinician. For the first time a DTC genetic testing company is advertising health-related reports "that meet [Food and Drug Administration] standards for being clinically and scientifically valid." Ethicists and regulatory agencies alike have recognized the need for a more informed transaction in the DTC context, but how should we classify a commercial transaction for something normally protected by a duty of care? How can we assure informed agreements in an industry with terms and conditions as varied as the services performed? The doctrine of "informed consent" began as an ethical construct building on the promise of beneficence in the clinical relationship and elevating the principle of autonomy--but in the DTC context should we hold providers to legal standards of informed consent and associated medical malpractice liability, or contractual obligations where consumers would seek remedy for breach? This Article analyzes the fine balance that must be struck in an industry where companies are selling services for entertainment or non-medical purposes that possess the capacity to produce serious and disquieting medical information. It begins by reviewing current standards of consent in the clinical setting from both a legal and ethical perspective and then lays forth current standards for DTC consent using two currently controversial case studies: that of keepsake fetal ultrasound and genetic testing. DTC keepsake ultrasound and genetic testing providers attempt to de-medicalize the devices used for these procedures from their intended medical uses to non-medical uses. But while keepsake ultrasound is marketed as "intended for entertainment purposes only," it can provide medical information as an incidental finding. 23andMe currently purports to be the only DTC genetics service that "includes" reports that meet FDA qualifications, despite disclaimers of intent to "provide medical advice." The attempted de-medicalization of these devices, therefore, has not been fully transformative, and DTC providers should have more robust ethical and legal duties than the average goods and services seller. This Article delineates these responsibilities, beginning with ethical duties surrounding marketing, entering into, and providing DTC services. It then turns to the legal paradigms necessary to enable, or at least allow for, DTC providers to meet these ethical obligations. While it argues that contractual, as opposed to fiduciary, requirements are most appropriate and that waivers of liability will likely be upheld, it also advocates for a heightened expectation of disclosure during contracting. PMID- 26863851 TI - "SINCE I MUST PLEASE THOSE BELOW": HUMAN SKELETAL REMAINS RESEARCH AND THE LAW. AB - The ethics of non-invasive scientific research on human skeletal remains are poorly articulated and lack a single, definitive analogue in western law. Laws governing invasive research on human fleshed remains, as well as bio-ethical principles established for research on living subjects, provide effective models for the establishment of ethical guidelines for non-invasive research on human skeletal remains. Specifically, non-invasive analysis of human remains is permissible provided that the analysis and collection of resulting data (1) are accomplished with respect for the dignity of the individual, (2) do not violate the last-known desire of the deceased, (3) do not adversely impact the right of the next of kin to perform a ceremonious and decent disposal of the remains, and (4) do not unduly or maliciously violate the privacy interests of the next of kin. PMID- 26863852 TI - THE HEALTH OF EBAY: THE IMPACT OF EBAY ON THE FUTURE OF TRIPS-LIKE PHARMACEUTICAL COMPULSORY LICENSES IN THE UNITED STATES. PMID- 26863853 TI - ANTI-AMEBIC ACTIVITY OF DIOSGENIN ON NAEGLERIA FOWLERI TROPHOZOITES. AB - The aim of this study was to investigate the activity of diosgenin against Naegleria fowleri trophozoites at the cellular and molecular levels. Diosgenin (100 MUg/ml; 241.2 MUM) had a 100% inhibitory effect on N. fowleri trophozoites (5 x 10(5) cell/ml). Scanning electron micrograph revealed diosgenin decreased the number of sucker-like apparatuses and food cup formation among N. fowleri trophozoites at 3 and 6 hours post-exposure, respectively. Diosgenin down regulated the nf cysteine protease gene expression of N. fowleri trophozoites at 6 and 12 hours post-exposure. The toxicity to mammalian cells caused by diosgenin at therapeutic dose was less than amphotericin B, the current drug used to treat N. fowleri infections. Our findings suggest diosgenin has activity against the surface membrane and the nf cysteine pro tease of N. fowleri trophozoites. However, the other mechanisms of action of diosgenin against N. fowleri trophozoites require further exploration. PMID- 26863854 TI - HUMAN GIARDIASIS IN MALAYSIA: CORRELATION BETWEEN THE PRESENCE OF CLINICAL MANIFESTATION AND GIARDIA INTESTINALIS ASSEMBLAGE. AB - Clinical manifestations of giardiasis vary from asymptomatic infection to chronic diarrhea. A total of 611 stool samples from Aboriginal participants residing in Jelebu, Gerik and Temerloh States, Malaysia, ages 2 to 74 years were screened for Giardia intestinalis using microscopic examination and sequence analysis of a fragment of nested-PCR amplified triosephosphate isomerase (tpi) gene. Demographic data was collected through a structured questionnaire. tpi was successfully amplified from 98/110 samples microscopically positive for G. intestinalis, with 62 and 36 belonging to assemblage A and B, respectively. There is a significant correlation between assemblage A and symptomatic infection only in participants of < 15 years of age. In the other age group, host factors may have more effects on the presence of clinical signs and symptoms than G. intestinalis assemblage types. PMID- 26863855 TI - PREVALENCE OF DIENTAMOEBA FRAGILIS AMONG AN ORANG ASLI POPULATION IN RURAL MALAYSIA. AB - Dientamoeba fragilis is a trichomonad parasite that can infect the gastrointestinal tract of humans causing gastrointestinal disease. Little is known about its epidemiology. We evaluated the prevalence of D. fragilis by conducting a cross sectional study of an Orang Asli population in rural Malaysia. We examined stool samples from 150 participants for D. fragilis using Wheatley's trichrome stain and collected demographic data from each participant using a structured questionnaire. Five participants (3.3%) had D. fragilis in their stool; four of these were aged < 15 years; 3 were male and 2 were female. All participants with positive stool sample for D. fragilis were symptomatic; 3 had diarrhea and 2 had other gastrointestinal symptoms. D. fragilis is present in the study population. Further studies are needed to determine the virulence, pathogenicity and mode of transmission of D. fragilis in the study population. PMID- 26863856 TI - ABSENCE OF AEDES AEGYPTI (L.) ON AN ECOLOGICAL ISLAND: COMPETITIVE EXCLUSION? AB - Ovitrap surveillance was conducted in 2012 and 2006 in Malay and Aboriginal Villages on Carey Island. In each village, standard ovitraps were placed indoors and outdoors at randomly selected houses/locations. All L3 larvae recovered were identified up to species level. Results demonstrated that only larvae of Aedes albopictus were found in all the positive ovitraps placed indoors and outdoors. In 2012, a high ovitrap index (OI) of 66.7% indoor and 84.0% outdoor in the Malay Village; and 62.5% indoor and 88.0% outdoor in Aboriginal Village with an apparent absence of Aedes aegypti. In 2006, a 100% OI was recorded in all ovitraps set indoors and outdoors in both villages. PMID- 26863858 TI - MALACOLOGICAL INVESTIGATION OF THE FULLY OPERATIONAL NAM THEUN 2 HYDROELECTRIC DAM PROJECT IN KHAMMOUANE PROVINCE, CENTRAL LAO PDR. AB - We conducted a malacological investigation in four districts of the Nam Theun 2 (NT2) hydroelectric dam project area, Khammouane Province, central Lao PDR (Nakai, Gnommalath, Mahaxai and Xe Bang Fai), after the first and second years of full operation in March 2010 and November 2011 to determine health risks for humans. A total 10,863 snail specimens (10 families/23 species) from 57 sampling stations and 12,902 snail specimens (eight families/21 species) from 66 sampling stations were collected in 2010 and 2011, respectively. Neotricula aperta (gamma race), the intermediate host for Schistosoma mekongi, was found in large numbers (5,853 specimens) in 2010 in Nam Gnom (downstream) at Station 25 (Mueang Gnommalath: Gnommalath District) and in fewer numbers (170 specimens) at Station 26 (Ban Thathod: Gnommalath District). In 2011, significantly fewer numbers (434 specimens) of N. aperta were found at Station 25. No snails were found to be infected with S. mekongi; however, 3.6% and 0.45% of Bithynia (D.). s. goniomphalos specimens collected were found to be infected with Opisthorchis viverrini (human liver fluke) during 2010 and 2011, respectively. Pomacea canaliculata, the rice crop pest, the intermediate host of Angiostrongylus (Parastrongylus) cantonensis, was found in the greatest numbers during 2010 and 2011; the prevalence increased significantly from 1.3% in 2010 to 53.3% in 2011. We also found seasonal variation in snail populations in terms of abundance and diversity. The snail fauna and risk for transmission of parasitic diseases need to be monitored continuously to evaluate the long-term impact of the dam project. PMID- 26863857 TI - SPECIES DIVERSITY AND SEASONALITY OF PHLEBOTOMINE SAND FLIES (DIPTERA: PSYCHODIDAE) IN SATUN PROVINCE, THAILAND. AB - Leishmaniasis is prevalent mainly in the southern provinces of Thailand where sand flies are considered to be an important vector. Sand flies were collected using Centers for Disease Control (CDC) light traps in Satun Province from June 2013 to July 2014. A total of 1,982 sand flies (1,228 females and 754 males) were collected. Only female sand flies were identified to the species level and were tested for Leishmania infection using polymerase chain reaction (PCR). Morphological identification revealed 2 genera and 9 species: Phlebotomus stantoni, P. argentipes, Sergentomyia gemmea, S. indica, S. barraudi, S. iyengari, S. bailyi, S. perturbans, and S. silvatica. S. gemmea (57.2%) was the most abundant species. The diversity of sand flies was highest in Thung Wa District. The sand flies were most abundant late in the hot season and early in the rainy season (April to June). The highest number of sand flies was collected in June. Significant correlations between the number of female sand flies and rainfall and between S. gemmea and rainfall were found. Of the female sand flies tested, none were positive for Leishmania spp. PMID- 26863859 TI - EFFECT OF HIV PREVENTION AND TREATMENT PROGRAM ON HIV AND HCV TRANSMISSION AND HIV MORTALITY AT AN INDONESIAN NARCOTIC PRISON. AB - Validated data regarding HIV-transmission in prisons in developing countries is scarce. We examined sexual and injecting drug use behavior and HIV and HCV transmission in an Indonesian narcotic prison during the implementation of an HIV prevention and treatment program during 2004-2007 when the Banceuy Narcotic Prison in Indonesia conducted an HIV transmission prevention program to provide 1) HIV education, 2) voluntary HIV testing and counseling, 3) condom supply, 4) prevention of rape and sexual violence, 5) antiretroviral treatment for HIV positive prisoners and 6) methadone maintenance treatment. During a first survey that was conducted between 2007 and 2009, new prisoners entered Banceuy Narcotics Prison were voluntary tested for HIV and HCV-infection after written informed consent was obtained. Information regarding sexual and injecting risk behavior and physical status were also recorded at admission to the prison. Participants who tested negative for both HIV and HCV during the first survey were included in a second survey conducted during 2008-2011. During both surveys, data on mortality among HIV-seropositive patients were also recorded. All HIV seropositive participants receive treatment for HIV. HIV/ AIDS-related deaths decreased: 43% in 2006, 18% in 2007, 9% in 2008 and 0% in 2009. No HIV and HCV seroconversion inside Banceuy Narcotic Prison were found after a median of 23 months imprisonment (maximum follow-up: 38 months). Total of 484.8 person-years observation was done. Participants reported HIV transmission risk-behavior in Banceuy Prison during the second survey was low. After implementation of HIV prevention and treatment program, no new HIV or HCV cases were detected and HIV related mortality decreased. PMID- 26863860 TI - DRUG-RESISTANT TUBERCULOSIS AMONG URBAN THAI CHILDREN: A 10-YEAR REVIEW. AB - Drug-resistant tuberculosis (DR-TB) has become an increasing public health concern. We conducted this retrospective chart review to determine the risk factors, susceptibility patterns, and clinical outcomes of children with DR-TB treated at the Queen Sirikit National Institute of Child Health, Bangkok, Thailand. Susceptibility results were available for 78 of the 91 patients (85.7%) with positive cultures for M. tuberculosis. Sensitivity of tuberculin skin testing for overall culture-confirmed tuberculosis with a cut-off point of 10 mm for human immunodeficiency virus (HIV)-uninfected cases was 76.9%. Using a 5-mm induration cut-off-point for tuberculin skin testing for HIV-infected cases, sensitivity was only 14.3%. Resistance to at least one anti-tubercular drug was found in 22 cases (28.2%), with streptomycin resistance being the most common (21.7%), followed by isoniazid (11.5%), rifampicin (5.1%), and ethambutol (5.1%). Multi-drug resistance (MDR) was observed in 3 cases (3.8%). A history of previous TB treatment and bone and joint involvement were associated with a significantly higher percentage of DR-TB: 18.2% vs 1.8% (p = 0.0078) and 22.7 vs 1.8% (p = 0.0018), respectively. Case fatality rates were 1.7% and 4.5% for drug susceptible and DR-TB, respectively. Due to the high rate of resistance, streptomycin is not recommended as first time treatment of childhood tuberculosis in Thailand. PMID- 26863861 TI - DETECTION AND MOLECULAR CHARACTERIZATION OF ENTEROAGGREGATIVE ESCHERICHIA COLI FROM DIARRHEAL PATIENTS IN TERTIARY HOSPITALS, SOUTHERN THAILAND. AB - Enteroaggregative Escherichia coli (EAEC) is a member of diarrheagenic E. coli, which plays an important role in human infections in developing countries. Investigations of EAEC in diarrheal patients at Hat-Yai and Pattani Hospitals, southern Thailand identified 5 EAEC strains, which were classified into serogroups, O44 and O127a. All 5 EAEC contained the global transcriptional regulator gene, aggR, and possessed fimbrial subunit genes, aggA and aafA, and EAEC-related toxin genes, astA and pet. PCR-based phylogenetic group assay revealed that the EAEC belonged to groups B1 and D. Low levels of clump formation were observed for all EAEC strains. Scanning electron microscopy showed an absence of fimbrial structure. DNA profiles generated by BOX- and ERIC2-PCR exhibited correspondingly identical patterns among all 5 EAEC strains, suggesting that they evolved from the same bacterial clone. Thus, there exists a low but still significant prevalence of EAEC-related diarrheal illnesses in the southern region of Thailand. PMID- 26863862 TI - EVALUATION OF RED BLOOD CELL INDICES RELATED DISORDERS AMONG ELIGIBLE BLOOD DONORS AT THE UNIVERSITI PUTRA MALAYSIA (UPM). AB - Pre-donation screening declarations and hemoglobin (Hb) testing are measures used to determine the quality of donated blood. The copper sulphate (CuSo4) method used to screen for blood abnormalities can give inaccurate results if strict quality control is not applied. Blood donors who are carriers of thalassemia and those with mild iron deficiency anemia (IDA) are usually asymptomatic and frequently missed at blood donation. The aim of this study was to evaluate the red blood cell (RBC) indices related disorders among blood donors who were deemed qualified to donate blood after screening with CuSo4 method. One hundred fifty eight volunteer blood donors at the Universiti Putra Malaysia (UPM), who had passed the CuSo4 screening method, were recruited for this study. Their bloods specimens were examined with a complete blood count. Subjects with a low mean corpuscular hemoglobin (MCH) level were examined further by checking a serum ferritin level, Hb quantification, and molecular analysis to examine for common RBC disorders. Fourteen point six percent of subjects had a low Hb level, two (1.3%) had IDA and four (2.5%) had thalassemia or some other hemoglobinopathy. Using a MCH level < 27 pg as a cut-off point, 58 subjects (36.7%) had suspected IDA, thalassemia or some other hemoglobinopathy. Eight point nine percent of subjects with a normal Hb level had thalassemia, and 3.8% had IDA. Malaysia has a high prevalence of thalassemia and other hemoglobinopathies. Pre-donation accurate screening is crucial to protect the quality of blood transfusion products. Public education regarding RBC disorders especially among blood donors is important. PMID- 26863863 TI - POSTTRAUMATIC STRESS DISORDER AMONG INDONESIAN CHILDREN 5 YEARS AFTER THE TSUNAMI. AB - Children are at risk for developing posttraumatic stress disorder (PTSD) due to experiencing or living in a disaster area. The factors that increase the likelihood of a child developing PTSD need further clarification. We studied the factors associated with PTSD among children who experienced the tsunami in Sumatra, Indonesia. We conducted a cross sectional study in 2 subdistricts of Sumatra 5 years after experiencing a tsunami. Children aged 7-13 years were enrolled using stratified cluster sampling. A tsunami-modified version of The PsySTART Rapid Triage System was used to question children about their tsunami specific traumatic experiences. Trauma symptoms were evaluated using the Trauma Symptom Checklist For Children (TSCC). The diagnosis of PTSD was made using the Child PTSD Symptom Scale (CPSS) and DSM-IV criteria. The data were analyzed with chi-square tests and multivariate logistic regression analysis with 95% confidence intervals (CI). A total of 262 children were enrolled in this study. The prevalence of PTSD in these children was 20.6%. On multivariate analysis, having experienced a delay in evacuation (PR = 4.5; 95% CI: 2.794-13.80; p < 0.001) and being unable to escape (PR = 13.07; 95% CI: 5.884-64; p < 0.001) were significantly associated with PTSD 5 years after the tsunami. Children who experienced a traumatic event in which they were unable to escape or when there is a delay in evacuation are at risk of developing PTSD and need appropriate treatment. PMID- 26863864 TI - RISK FACTORS AND INCIDENCE OF FALLS AMONG FIFTH- AND SIXTH-GRADE CHILDREN IN SEOUL, SOUTH KOREA. AB - This study aimed to determine the incidence of falls among children in South Korea, and the risk factors associated with these falls in order to develop preventive strategies. We studied 1,044 elementary school students in the fifth and sixth grades from Seoul, South Korea and evaluated the incidence of falls based on four surveys conducted in June, September, and December 2010 and February 2011. The surveys included the number of falls, the types of medical care received, and the potential factors associated with those falls. Risk factors related to the falls were examined using a generalized estimating equation method. Statistical analysis was performed using SAS, version 9.2. The overall incidence of falls was 376 per 1,000 person-years; and a total of 44 children were hospitalized. Having a previous history of fall [odds ratio (OR) = 1.33; 95% confidence interval (CI): 1.08-1.64] and attention deficit hyperactivity disorder (ADHD) (OR = 3.63; 95% CI: 2.97-4.44) were risk factors associated with falls. Comparative analyses of the odds of having a single fall versus recurrent falls showed that ADHD (p < 0.001) and overweight/obesity (p = 0.004) were significantly associated with risk of recurrent falls. These results suggest novel safety programs should be developed taking these risk factors into consideration in order to reduce the incidence of falls among children in South Korea. PMID- 26863865 TI - BREAKFAST CONSUMPTION BEHAVIORS OF ELEMENTARY SCHOOL CHILDREN IN BANGKOK METROPOLITAN REGION. AB - Family factors influence children's eating behavior. However, there is little research on family correlates of children's breakfast behavior. This study investigated the breakfast consumption behaviors of school-aged children by surveying their parents. One thousand twelve parents of Grade 1-6 students in Bangkok Metropolitan region completed the questionnaire comprising the following topics: general information about parents, general information about school children, parents' knowledge of breakfast consumption, and breakfast consumption behavior in school children. The results indicated that parents did play a role in breakfast preparation. The earlier parents woke up, the higher the chance of children to have breakfast. Most parents (83%) had good knowledge about breakfast goodness. Just over three-quarters (79%) of students had a breakfast daily; with only 1% that never had breakfast daily. Frequency of breakfast consumption tended to decreases, as children growing up. The key barrier of breakfast consumption were lack of time, woke up late, and had no breakfast prepared at home. Without breakfast, the parents reported that their children expressed hunger, moodiness, and the inability to concentrate in class. PMID- 26863866 TI - USING THE DELPHI TECHNIQUE TO DEVELOP EFFECTIVENESS INDICATORS FOR SOCIAL MARKETING COMMUNICATION TO REDUCE HEALTH-RISK BEHAVIORS AMONG YOUTH. AB - This study aimed to develop effectiveness indicators for social marketing communication to reduce health-risk behaviors among Thai youth by using the Delphi technique. The Delphi technique is a research approach used to gain consensus through a series of two or more rounds of questionnaire surveys where information and results are fed back to panel members between each round and it has been extensively used to generate many indicators relevant to health behaviors. The Delphi technique was conducted in 3 rounds by consulting a panel of 15 experts in the field of social marketing communication for public health campaigns in Thailand. We found forty-nine effectiveness indicators in eight core components reached consensus. These components were: 1) attitude about health risk behavior reduction, 2) subjective norms, 3) perceived behavioral control, 4) intention to reduce health-risk behaviors, 5) practices for reducing health-risk behaviors, 6) knowledge about the dangers and impact of health-risk behaviors, 7) campaign brand equity, and 8) communication networks. These effectiveness indicators could be applied by health promotion organizations for evaluating the effectiveness of social marketing communication to effectively reduce health-risk behaviors among youth. PMID- 26863867 TI - Progressive postresection program (pPRP) after pancreatic resection: study protocol for a randomized controlled trial. AB - BACKGROUND: At the time of initial diagnosis, only 15-20% of patients with pancreatic cancer present with a resectable disease. Patients with pancreatic cancer face a poor prognosis. Progression-free survival and overall survival rates are very limited, so it is important to develop concepts to improve the quality of life for their remaining lives. METHODS/DESIGN: The proposed trial is a randomized controlled intervention study. After pancreatic resection, the intervention group (cohort A, n = 30 patients) will take part in an intensified physiotherapy program consisting of endurance and muscle force exercises. The control group (cohort B, n = 30 patients) will take part in standard physiotherapy. Both groups will receive dietary counseling and, if necessary, substitution for endocrine/exocrine pancreatic insufficiency. Quality of life will be evaluated using the Short Form-8 Health Survey and the European Organization for Research and Treatment of Cancer QLQ-C30/QLQ-PAN26 questionnaires. DISCUSSION: The aim of this study is to investigate whether intensive physiotherapy improves the quality of life of patients after pancreatic resection. If the results for the intervention group are positive, a multicenter study should be performed with appropriate statistical power. The progressive postresection program includes a structured follow-up after pancreatic resection. In this study, all patients will undergo abdominal computed tomography for follow up 6 and 12 months postoperatively. TRIAL REGISTRATION: German Clinical Trials Register DRKS00006786. Date of registration 1 October 2014. PMID- 26863868 TI - Leveraging workflow control patterns in the domain of clinical practice guidelines. AB - BACKGROUND: Clinical practice guidelines (CPGs) include recommendations describing appropriate care for the management of patients with a specific clinical condition. A number of representation languages have been developed to support executable CPGs, with associated authoring/editing tools. Even with tool assistance, authoring of CPG models is a labor-intensive task. We aim at facilitating the early stages of CPG modeling task. In this context, we propose to support the authoring of CPG models based on a set of suitable procedural patterns described in an implementation-independent notation that can be then semi-automatically transformed into one of the alternative executable CPG languages. METHODS: We have started with the workflow control patterns which have been identified in the fields of workflow systems and business process management. We have analyzed the suitability of these patterns by means of a qualitative analysis of CPG texts. Following our analysis we have implemented a selection of workflow patterns in the Asbru and PROforma CPG languages. As implementation-independent notation for the description of patterns we have chosen BPMN 2.0. Finally, we have developed XSLT transformations to convert the BPMN 2.0 version of the patterns into the Asbru and PROforma languages. RESULTS: We showed that although a significant number of workflow control patterns are suitable to describe CPG procedural knowledge, not all of them are applicable in the context of CPGs due to their focus on single-patient care. Moreover, CPGs may require additional patterns not included in the set of workflow control patterns. We also showed that nearly all the CPG-suitable patterns can be conveniently implemented in the Asbru and PROforma languages. Finally, we demonstrated that individual patterns can be semi-automatically transformed from a process specification in BPMN 2.0 to executable implementations in these languages. CONCLUSIONS: We propose a pattern and transformation-based approach for the development of CPG models. Such an approach can form the basis of a valid framework for the authoring of CPG models. The identification of adequate patterns and the implementation of transformations to convert patterns from a process specification into different executable implementations are the first necessary steps for our approach. PMID- 26863870 TI - Explanations and information-giving: clinician strategies used in talking to parents of preterm infants. AB - BACKGROUND: The study is part of a larger research programme on neonatal brain imaging in the trial element of which parents were randomised to receive prognostic information based upon either magnetic resonance imaging (MRI) or ultrasound findings (ePrime study). The aim of this study was to investigate the strategies used by clinicians in communicating with parents following imaging at term age of the brain of preterm infants born before 33 weeks gestation, focusing on explanations and information-giving about prognosis METHOD: Audio recordings of discussions between parents and clinicians were made following MRI and ultrasound assessment. Parents were given the scan result and the baby's predicted prognosis. A framework was developed based on preliminary analysis of the recordings and findings of other studies of information-giving in healthcare. Communication of scan results by the clinicians was further explored in qualitative analysis with 36 recordings using NVivo 10 and the specifically developed framework. Emerging themes and associated sub-themes were identified. RESULTS: The ways in which clinicians gave information and helped parents to understand were identified. Within the over-arching theme of clinician strategies a wide range of approaches were used to facilitate parental understanding. These included orienting, checking on previously acquired information, using analogies, explaining terminology, pacing the information, confirming understanding, inviting clarification, answering parents' questions and recapping at intervals. Ultimately four key themes were identified: 'Framing the information-giving', 'What we are looking at', 'Presenting the numbers and explaining the risk' and 'Appreciating the position of parents'. CONCLUSIONS: The interviews represent a multifaceted situation in which there is a tension between the need to explain and inform and the inherent complexity of neurological development, potential problems following preterm birth and the technology used to investigate and monitor these. PMID- 26863872 TI - Implementation of distress screening in an oncology setting. AB - The recommendations of numerous groups, such as the Institute of Medicine and the National Comprehensive Cancer Network, have resulted in the first regulatory standard on distress screening in oncology implemented in 2015 by the American College of Surgeons Commission on Cancer. This practice-changing standard promises to result in better quality cancer care, but presents unique challenges to many centers struggling to provide high-quality practical assessment and management of distress. The current paper reviews the history behind the CoC standard, identifies the most prevalent symptoms underlying distress, and discusses the importance of distress screening. We also review some commonly used instruments for assessing distress, and address barriers to implementation of screening and management. PMID- 26863869 TI - On the role of ethylene, auxin and a GOLVEN-like peptide hormone in the regulation of peach ripening. AB - BACKGROUND: In melting flesh peaches, auxin is necessary for system-2 ethylene synthesis and a cross-talk between ethylene and auxin occurs during the ripening process. To elucidate this interaction at the transition from maturation to ripening and the accompanying switch from system-1 to system-2 ethylene biosynthesis, fruits of melting flesh and stony hard genotypes, the latter unable to produce system-2 ethylene because of insufficient amount of auxin at ripening, were treated with auxin, ethylene and with 1-methylcyclopropene (1-MCP), known to block ethylene receptors. The effects of the treatments on the different genotypes were monitored by hormone quantifications and transcription profiling. RESULTS: In melting flesh fruit, 1-MCP responses differed according to the ripening stage. Unexpectedly, 1-MCP induced genes also up-regulated by ripening, ethylene and auxin, as CTG134, similar to GOLVEN (GLV) peptides, and repressed genes also down-regulated by ripening, ethylene and auxin, as CTG85, a calcineurin B-like protein. The nature and transcriptional response of CTG134 led to discover a rise in free auxin in 1-MCP treated fruit. This increase was supported by the induced transcription of CTG475, an IAA-amino acid hydrolase. A melting flesh and a stony hard genotype, differing for their ability to synthetize auxin and ethylene amounts at ripening, were used to study the fine temporal regulation and auxin responsiveness of genes involved in the process. Transcriptional waves showed a tight interdependence between auxin and ethylene actions with the former possibly enhanced by the GLV CTG134. The expression of genes involved in the regulation of ripening, among which are several transcription factors, was similar in the two genotypes or could be rescued by auxin application in the stony hard. Only GLV CTG134 expression could not be rescued by exogenous auxin. CONCLUSIONS: 1-MCP treatment of peach fruit is ineffective in delaying ripening because it stimulates an increase in free auxin. As a consequence, a burst in ethylene production speeding up ripening occurs. Based on a network of gene transcriptional regulations, a model in which appropriate level of CTG134 peptide hormone might be necessary to allow the correct balance between auxin and ethylene for peach ripening to occur is proposed. PMID- 26863871 TI - The clock drawing test as a screening tool in mild cognitive impairment and very mild dementia: a new brief method of scoring and normative data in the elderly. AB - many studies sustained that the clock drawing test (CDT) was not able to accurately detect people with CDR = 0.5. Other researchers have promoted the use of scoring approaches with multiple scales that rate quantitative and qualitative features of the production. Nevertheless, these scoring systems are complex and time-consuming. We propose a new brief CDT' scoring system in order to find a good measure for mild cognitive decline which is at the same time easy to administer. we enrolled 719 subjects: n. 181 with mild Alzheimer's disease (AD); n. 200 with amnesic mild cognitive impairment (MCI) and n. 338 healthy elderly subjects (C). our CDT-three-cluster scoring system demonstrated a good sensitivity and an excellent specificity to discriminate MCI subjects from normal elderly (76 and 84 %, respectively) and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer disease (CDR: 1) from normal elderly (91 and 90 %, respectively). We found that CDT' score = 1.30 discriminate people with MCI, whereas a score = 4.38 discriminate AD patients. The three cluster-scoring-system demonstrated a good diagnostic accuracy, taking into account those error-items more predictive of cognitive decline: omission of numbers or hands, writing numbers or hands in a wrong position and writing numbers or hands in a different code. Our CDT' scoring system is very short and easy method which can be used also by non-specialist. PMID- 26863873 TI - Cancer clinical trial enrollment of diverse and underserved patients within an urban safety net hospital. AB - BACKGROUND: Enrollment rates onto cancer clinical trials are low and reflect a small subset of the population of which even fewer participants come from populations of racial or ethnic diversity or low socioeconomic status. There is a need to increase enrollment onto cancer clinical trials with a focus on recruitment of a diverse, underrepresented patient population. OBJECTIVE: To use the electronic medical record (EMR) to understand the eligibility and enrollment rates for all available cancer trials in the ambulatory care setting at an urban safety net hospital to identify specific strategies for enhanced accrual onto cancer clinical trials of diverse and underserved patients. METHODS: A clinical trial screening note was created for the EMR by the clinical trials office at an urban safety net hospital. 847 cancer clinical trial screening notes were extracted from the EMR between January 1, 2010 and December 31, 2010. During that time, 99 cancer trials were registered for accrual, including clinical treatment, survey, data repository, imaging, and symptom management trials. Data on eligibility, enrollment status, and relationship to sociodemographic status were compared. LIMITATIONS: This is a single-institution and retrospective study. CONCLUSIONS: The findings demonstrate that a formal process of tracking cancer clinical trial screens using an EMR can document baseline rates of institution specific accrual patterns and identify targeted strategies for increasing cancer clinical trial enrollment among a vulnerable patient population. Offering nontreatment trials may be an important and strategic method of engaging this vulnerable population in clinical research. PMID- 26863874 TI - Racial disparities in breast cancer diagnosis in Central Georgia in the United States. AB - BACKGROUND: Mortality rates in breast cancer are worse for African Americans than for whites. OBJECTIVE: To investigate the presence of racial disparities in clinical staging in women diagnosed with breast cancer and understand whether such disparities exist in Central Georgia in the United States. METHODS: We retrospectively reviewed records from the Tumor Registry of the Medical Center Navicent Health in Macon, Georgia, of women who had been diagnosed with breast cancer during 2011-2013. The chi-square test was used to assess statistically significant differences between whites and African Americans. We also assessed the patients' health insurance status and age at diagnosis. RESULTS: A total of 578 participants were identified. Statistically significant differences existed in the clinical stage between the races (?? = .0003). Whites were more often clinical stage I at diagnosis, whereas African Americans had a greater percentage of stages II, III, or IV. African Americans were more than twice as likely to be diagnosed at clinical stage IV than were their white counterparts. Statistical differences also existed with age at diagnosis (?? = .0066) and insurance coverage (?? = .0004). A greater percentage of white patients were aged 65 years or older at diagnosis, whereas a greater percentage of African American patients were aged 49 years or younger. A greater percentage of African Americans had Medicaid insurance, whereas a greater percentage of whites had private health insurance. LIMITATIONS: As a single-center study, it is difficult to generalize these results elsewhere. Furthermore, this study focused on association and not on causation. It is difficult to pinpoint why such disparities exist. CONCLUSIONS: The etiology of racial disparities between African American and white women with breast cancer seems to be multifaceted. Screening mammography remains an important tool for identifying breast cancer. Low socioeconomic and educational status as well as a lack of a primary care physician may play a role in these disparities. Other factors that may have a role include biological factors and possible mistrust of the health care system. PMID- 26863875 TI - Sexual health assessment and counseling: oncology nurses' perceptions, practices, and perceived barriers. AB - BACKGROUND: Cancer-related sexual dysfunction has a negative impact on patient quality of life. OBJECTIVE: To describe oncology nurses' perceptions, practices, and perceived barriers regarding sexual health assessment and counseling. METHODS: In 2005, a 31-item questionnaire was mailed to 56 oncology nurses employed at 6 regional cancer care centers in northern, central, and western Wisconsin. Questions captured demographic information about the nurses and information about attitudes, perceptions, and practice patterns regarding patient sexual health counseling, and the barriers to discussing sexuality with patients. RESULTS: Nearly 70% of mailed surveys were returned completed. Most of the respondents believed that sexual health concerns were important and that it was appropriate for nurses to discuss patient sexual concerns, but less than one third of the nurses said they had offered to discuss sexual concerns with patients in the previous 12 months. Few respondents reported feeling adequately knowledgeable about talking to patients about concerns about sexual health, and more than 90% thought that additional training in sexual health counseling would increase their confidence in addressing sexual health issues. LIMITATIONS: Study findings are limited by validity of the survey instrument and issues related to self-report. Sensitivity of the topic may have resulted in selection bias. CONCLUSIONS: Sexual health among patients with cancer was recognized as important, but was discussed infrequently. Additional training may improve the ability of oncology nurses to provide sexual health counseling to patients. PMID- 26863876 TI - The cag-pathogenicity island encoded CncR1 sRNA oppositely modulates Helicobacter pylori motility and adhesion to host cells. AB - Small regulatory RNAs (sRNAs) are emerging as key post-transcriptional regulators in many bacteria. In the human pathobiont Helicobacter pylori a plethora of trans and cis-encoded sRNAs have been pinpointed by a global transcriptome study. However, only two have been studied in depth at the functional level. Here we report the characterization of CncR1, an abundant and conserved sRNA encoded by the virulence-associated cag pathogenicity island (cag-PAI) of H. pylori. Growth phase dependent transcription of CncR1 is directed by the PcagP promoter, which resulted to be a target of the essential transcriptional regulator HsrA (HP1043). We demonstrate that the 213 nt transcript arising from this promoter ends at an intrinsic terminator, few bases upstream of the annotated cagP open reading frame, establishing CncR1 as the predominant gene product encoded by the cagP (cag15) locus. Interestingly, the deletion of the locus resulted in the deregulation en masse of sigma(54)-dependent genes, linking CncR1 to flagellar functions. Accordingly, the enhanced motility recorded for cncR1 deletion mutants was complemented by ectopic reintroduction of the allele in trans. In silico prediction identified fliK, encoding a flagellar checkpoint protein, as likely regulatory target of CncR1. The interaction of CncR1 with the fliK mRNA was thus further investigated in vitro, demonstrating the formation of strand-specific interactions between the two RNA molecules. Accordingly, the full-length translational fusions of fliK with a lux reporter gene were induced in a cncR1 deletion mutant in vivo. These data suggest the involvement of CncR1 in the post transcriptional modulation of H. pylori motility functions through down regulation of a critical flagellar checkpoint factor. Concurrently, the cncR1 mutant revealed a decrease of transcript levels for several H. pylori adhesins, resulting in a phenotypically significant impairment of bacterial adhesion to a host gastric cell line. The data presented support a model in which the cag-PAI encoded CncR1 sRNA is able to oppositely modulate bacterial motility and adhesion to host cells. PMID- 26863877 TI - Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations. AB - Studies indicate that exercise might delay human biological aging, but the effects of long-term exercise on T cell function are not well known. We tested the hypothesis that moderate or intense exercise lifestyle may attenuate the effects of aging on the telomere length and the survival and composition of T cell subpopulations. Elderly (65-85 years) with intense training lifestyle (IT, n = 15), moderate training lifestyle (MT, n = 16), and who never trained (NT, n = 15) were studied. Although the three groups presented the age-associated contraction of the TCD4(+)/TCD8(+) naive compartments and expansion of the memory compartments, both training modalities were associated with lower proportion of terminally differentiated (CD45RA(+)CCR7(neg)) TCD4(+) and TCD8(+) cells, although among the latter cells, the reduction reached statistical significance only with IT. MT was associated with higher proportion of central memory TCD4(+) cells, while IT was associated with higher proportion of effector memory TCD8(+) cells. However, both training lifestyles were unable to modify the proportion of senescent (CD28(neg)) TCD8(+) cells. Telomeres were longer in T cells in both training groups; with IT, telomere length increased mainly in TCD8(+) cells, whereas with MT, a modest increase in telomere length was observed in both TCD8(+) and TCD4(+) cells. Reduced commitment to apoptosis of resting T cells, as assessed by caspase-3 and Bcl-2 expression, was seen predominantly with IT. Measurement of pro-inflammatory cytokines in serum and peripheral blood mononuclear cell (PBMC)'s supernatants did not show chronic low-grade inflammation in any of the groups. In conclusion, MT and IT lifestyles attenuated some of the effects of aging on the immune system. PMID- 26863879 TI - Design and Synthesis of Some Novel Estrogen Receptor Modulators as Anti-Breast Cancer Agents: In Vitro & In Vivo Screening, Docking Analysis. AB - A series of novel coumarin-chalcone hybrids have been synthesized in good yields and evaluated for their in vitro & in vivo anticancer activity. Cytotoxicity study was done against MCF-7 and Zr-75-1 human cancer cell lines. All compounds exhibited significant antiproliferative properties on both cell lines. The most active ER modulators found in in vitro screening are subjected for in vivo screened using methyl nitrosourea (MNU) induced mammary carcinoma in female spraque dawley rats. The Glide XP docking was performed for designed scaffold to optimize its structural requirement for ER-alpha inhibition. PMID- 26863878 TI - Cerebrospinal fluid lactate is associated with multiple sclerosis disease progression. AB - BACKGROUND: Altered cerebrospinal fluid (CSF) levels of lactate have been described in neurodegenerative diseases and related to mitochondrial dysfunction and neuronal degeneration. We investigated the relationship between CSF lactate levels, disease severity, and biomarkers associated with neuroaxonal damage in patients with multiple sclerosis (MS). METHODS: One-hundred eighteen subjects with relapsing-remitting multiple sclerosis (RRMS) were included, along with one hundred fifty seven matched controls. CSF levels of lactate, tau protein, and neurofilament light were detected at the time of diagnosis. Patients were followed-up for a mean of 5 years. Progression index (PI), multiple sclerosis severity scale (MSSS), and Bayesian risk estimate for multiple sclerosis (BREMS) were assessed as clinical measures of disease severity and progression. Differences between groups and correlation between CSF lactate, disease severity and CSF biomarkers of neuronal damage were explored. RESULTS: CSF lactate was higher in RRMS patients compared to controls. A negative correlation was found between lactate levels and disease duration. Patients with higher CSF lactate concentration had significantly higher PI, MSSS, and BREMS scores at long-term follow-up. Furthermore, CSF lactate correlated positively and significantly with CSF levels of both tau protein and neurofilament light protein. CONCLUSIONS: Measurement of CSF lactate may be helpful, in conjunction with other biomarkers of tissue damage, as an early predictor of disease severity in RRMS patients. A better understanding of the alterations of mitochondrial metabolic pathways associated to RRMS severity may pave the way to new therapeutic targets to contrast axonal damage and disease severity. PMID- 26863880 TI - Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T. AB - Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated. PMID- 26863881 TI - 5' Adenosine Monophosphate-Activated Protein Kinase Modulators as Anticancer Agents. AB - In spite of tremendous advancement in the field of cancer therapy, it is still one of the leading causes of death worldwide. One of the newest targets in the field of cancer therapeutics is 5'Adenosine Mono Phosphate activated protein kinase (AMPK). In vitro and in vivo evidences suggest anti-cancer activity of AMPK. AMPK activation may promote catabolism while preventing the anabolic processes of cell. Thus it may modulate cellular protein and lipid metabolism and affect the growth and division of cell. Here we review the mechanisms of action of AMPK modulators as future anti-cancer agents. PMID- 26863882 TI - Cucurbitacin B Enhances the Anticancer Effect of Imatinib Mesylate Through Inhibition of MMP-2 Expression in MCF-7 and SW480 Tumor Cell Lines. AB - The combination of medicinal plant extracts with known chemotherapeutics offers significant potential for the development of novel therapies in cancer disease. Cucurbitacin B (CuB) is one of the most potent and widely used members of cucurbitacin family and it is known to have important effects on several diseases including cancer. To determine whether CuB can enhance chemosensitivity to imatinib mesylate (IM), in the present study, the combined effects of CuB with IM on MCF-7 and SW480 cells were investigated. The cells were treated with CuB alone or in combination with IM and the results showed that the combination treatment synergistically inhibited cell proliferation and induced apoptosis. Furthermore, the combined effect of CuB and IM on matrix metalloproteinase-2 (MMP-2) gene expression, a member of MMP family which is responsible for the degradation of extracellular matrix was also evaluated. CuB increased the inhibitory effect of IM on MMP-2 expression synergistically in a dose dependent manner. The results suggest that CuB in combination with IM may serve as a potentially useful therapeutic strategy for patients with breast and colorectal cancer. PMID- 26863883 TI - Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer? AB - Marine ecosystem represents a wide and untapped reservoir of biologically active metabolites. Most of the sponges, seaweeds, crustaceans, fish species and their associated microorganisms have evolved chemical means in order to defend themselves against predation and to survive in the complex marine environment. Such chemical and biological adaptation produced many bioactive substances with beneficial effects on human health, including potential anticancer agents. With further exploration of sea and ocean environment, several marine bioactives have been identified with promising anticancer activity. More than one hundred novel bioactive compounds with antitumor activity and their synthetic derivative substances displayed in vitro cytotoxic property on neoplastic cell lines and are currently gaining great attention for further evaluations and in vivo applications. This review highlights novel marine molecules and compounds which have been able to inhibit different cancer species in the recent years and aims to describe research on new natural antineoplastic agents obtained from sea world. PMID- 26863884 TI - Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer. AB - Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. beta-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. beta-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of beta-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation. PMID- 26863885 TI - Caffeine improves muscular performance in elite Brazilian Jiu-jitsu athletes. AB - Scientific information about the effects of caffeine intake on combat sport performance is scarce and controversial. The aim of this study was to investigate the effectiveness of caffeine to improve Brazilian Jiu-jitsu (BJJ)-specific muscular performance. Fourteen male and elite BJJ athletes (29.2 +/- 3.3 years; 71.3 +/- 9.1 kg) participated in a randomized double-blind, placebo-controlled and crossover experiment. In two different sessions, BJJ athletes ingested 3 mg kg(-1) of caffeine or a placebo. After 60 min, they performed a handgrip maximal force test, a countermovement jump, a maximal static lift test and bench-press tests consisting of one-repetition maximum, power-load, and repetitions to failure. In comparison to the placebo, the ingestion of the caffeine increased: hand grip force in both hands (50.9 +/- 2.9 vs. 53.3 +/- 3.1 kg; respectively p < .05), countermovement jump height (40.6 +/- 2.6 vs. 41.7 +/- 3.1 cm; p = .02), and time recorded in the maximal static lift test (54.4 +/- 13.4 vs. 59.2 +/- 11.9 s; p < .01).The caffeine also increased the one-repetition maximum (90.5 +/- 7.7 vs. 93.3 +/- 7.5 kg; p = .02), maximal power obtained during the power-load test (750.5 +/- 154.7 vs. 826.9 +/- 163.7 W; p < .01) and mean power during the bench-press exercise test to failure (280.2 +/- 52.5 vs. 312.2 +/- 78.3 W; p = .04). In conclusion, the pre-exercise ingestion of 3 mg kg(-1) of caffeine increased dynamic and isometric muscular force, power, and endurance strength in elite BJJ athletes. Thus, caffeine might be an effective ergogenic aid to improve physical performance in BJJ. PMID- 26863886 TI - Hypothyroidism and hyperthyroidism and breast cancer risk: a nationwide cohort study. AB - OBJECTIVE: The association between thyroid disease and breast cancer risk remains unclear. We, therefore examined the association between hypothyroidism, hyperthyroidism and breast cancer risk. DESIGN: This was a population-based cohort study. METHODS: Using nationwide registries, we identified all women in Denmark with a first-time hospital diagnosis of hypothyroidism or hyperthyroidism, 1978-2013. We estimated the excess risk of breast cancer among patients with hypothyroidism or hyperthyroidism compared with the expected risk in the general population, using standardized incidence ratios (SIRs) as a measure of risk ratio. Breast cancer diagnoses in the first 12 months following diagnosis of thyroid disease were excluded from the calculations to avoid diagnostic work-up bias. RESULTS: We included 61, 873 women diagnosed with hypothyroidism and 80, 343 women diagnosed with hyperthyroidism. Median follow-up time was 4.9 years (interquartile range (IQR): 1.8-9.5 years) for hypothyroidism and 7.4 years (IQR: 3.1-13.5 years) for hyperthyroidism. Hyperthyroidism was associated with a slightly increased breast cancer risk compared with the general population (SIR: 1.11, 95% CI: 1.07-1.16), which persisted beyond 5 years of follow-up (SIR: 1.13, 95% CI: 1.08-1.19). In comparison, hypothyroidism was associated with a slightly lower risk of breast cancer (SIR: 0.94, 95% CI: 0.88 1.00). Stratification by cancer stage at diagnosis, estrogen receptor status, age, comorbidity, history of alcohol-related disease and clinical diagnoses of obesity produced little change in cancer risk. CONCLUSIONS: We found an increased risk of breast cancer in women with hyperthyroidism and a slightly decreased risk in women with hypothyroidism indicating an association between thyroid function level and breast cancer risk. PMID- 26863887 TI - Occupational exposure to mould and microbial metabolites during onion sorting- insights into an overlooked workplace. AB - Manual sorting of onions is known to be associated with a bioaerosol exposure. The study aimed to gain an initial indication as to what extent manual sorting of onions is also associated with mycotoxin exposure. Twelve representative samples of outer onion skins from different onion origins were sampled and analyzed with a multimycotoxin method comprising 40 mycotoxins using a single extraction step followed by liquid chromatography with electrospray ionization and triple quadrupole mass spectrometry. Six of the 12 samples were positive for mycotoxins. In those samples, deoxynivalenol, fumonisin B1, and B2 were observed in quantitatively detectable amounts of 3940 ng/g for fumonisin B1 and in the range of 126-587 ng/g for deoxynivalenol and 55-554 ng/g for fumonisin B2. Although the results point to a lower risk due to mycotoxins, the risk should not be completely neglected and has to be considered in the risk assessment. PMID- 26863888 TI - Impact of pharmacists as immunizers on influenza vaccination coverage in Nova Scotia, Canada. AB - Immunization coverage in Canada has continued to fall below national goals. The addition of pharmacists as immunizers may increase immunization coverage. This study aimed to compare estimated influenza vaccine coverage before and after pharmacists began administering publicly funded influenza immunizations in Nova Scotia, Canada. Vaccination coverage rates and recipient demographics for the influenza vaccination seasons 2010-2011 to 2012-2013 were compared with the 2013 2014 season, the first year pharmacists provided immunizations. In 2013-2014, the vaccination coverage rate for those >=5 years of age increased 6%, from 36% in 2012-2013 to 42% (p<0.001). Pharmacists administered over 78,000 influenza vaccinations, nearly 9% of the province's population over the age of five. Influenza vaccine coverage rates for those >=65 increased by 9.8% (p<0.001) in 2013-2014 compared to 2012-2013. Influenza vaccination coverage in Nova Scotia increased in 2013-2014 compared to previous years with a universal influenza program. Various factors may have contributed to the increased coverage, including the addition of pharmacists as immunizers and media coverage of influenza related fatalities. Future research will be necessary to fully determine the impact of pharmacists as immunizers. PMID- 26863889 TI - Use of Polyvinyl Alcohol as a Solubility Enhancing Polymer for Poorly Water Soluble Drug Delivery (Part 2). AB - The KinetiSol(r) Dispersing (KSD) technology has enabled the investigation into the use of polyvinyl alcohol (PVAL) as a concentration enhancing polymer for amorphous solid dispersions. Our previous study revealed that the 88% hydrolyzed grade of PVAL was optimal for itraconazole (ITZ) amorphous compositions with regard to solid-state properties, non-sink dissolution performance, and bioavailability enhancement. The current study investigates the influence of molecular weight for the 88% hydrolyzed grades of PVAL on the properties of KSD processed ITZ:PVAL amorphous dispersions. Specifically, molecular weights in the processable range of 4 to 18 mPa . s were evaluated and the 4-88 grade provided the highest AUC dissolution profile. Amorphous dispersions at 10, 20, 30, 40, and 50% ITZ drug loads in PVAL 4-88 were also compared by dissolution performance. Analytical tools of diffusion-ordered spectroscopy and Fourier transform infrared spectroscopy were employed to understand the interaction between drug and polymer. Finally, results from a 30-month stability test of a 30% drug loaded ITZ:PVAL 4-88 composition shows that stable amorphous dispersions can be achieved. Thus, this newly enabled polymer carrier can be considered a viable option for pharmaceutical formulation development for solubility enhancement. PMID- 26863890 TI - Investigation of Possible Maillard Reaction Between Acyclovir and Dextrose upon Dilution Prior to Parenteral Administration. AB - In this study the stability of parenteral acyclovir (ACV) when diluted in dextrose (DEX) as large volume intravenous fluid preparation (LVIF) was evaluated and the possible Maillard reaction adducts were monitored in the recommended infusion time. Different physicochemical methods were used to evaluate the Maillard reaction of dextrose with ACV to track the reaction in real infusion condition. Other large volume intravenous fluids were checked regarding the diluted drug stability profile. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and mass data proved the reaction of glucose with dextrose. A Maillard-specific high performance liquid chromatography (HPLC) method was used to track the reaction in real infusion condition in vitro. The nucleophilic reaction occurred in diluted parenteral preparations of acyclovir in 5% dextrose solutions. The best diluent solution was also selected as sodium chloride and introduced based on drug stability and also its adsorption onto different infusion sets (PVC or non PVC) to provide an acceptable administration protocol in clinical practices. Although, the Maillard reaction was proved and successfully tracked in diluted solutions, and the level of drug loss when diluted in dextrose was reported to be between 0.27 up to 1.03% of the initial content. There was no drug adsorption to common infusion sets. The best diluent for parenteral acyclovir is sodium chloride large volume intravenous fluid. PMID- 26863891 TI - 19F Nuclear Magnetic Resonance Spectrometric Determination of the Partition Coefficients of Flutamide and Nilutamide (Antiprostate Cancer Drugs) in a Lipid Nano-Emulsion and Prediction of Its Encapsulation Efficiency for the Drugs. AB - To design a useful lipid drug carrier having a high encapsulation efficiency (EE%) for the antiprostate cancer drugs flutamide (FT) and nilutamide (NT), a lipid nano-emulsion (LNE) was prepared with soybean oil (SO), phosphatidylcholine (PC), and sodium palmitate, and the partition coefficients (K ps) of the drugs for the LNE were determined by 19F nuclear magnetic resonance (NMR) spectrometry. The 19F NMR signal of the trifluoromethyl group of both drugs showed a downfield shift from an internal standard (trifluoroethanol) and broadening according to the increase in the lipid concentration due to their interaction with LNE particles. The difference in the chemical shift (Deltadelta) of each drug caused by the addition of LNE was measured under different amounts of LNE, and the K p values were calculated from the Deltadelta values. The results showed that FT has higher lipophilicity than NT. The total lipid concentration (SO + PC) required to encapsulate each drug into LNE with an EE% of more than 95% was calculated from the K p values as 93.3 and 189.9 mmol/L for FT and NT, respectively. For an LNE prepared with the total lipid concentration of 215 mmol/L, the predicted EE% values were 98 and 96% for FT and NT, respectively, while the experimental EE% values determined by a centrifugation method were approximately 99% for both drugs. Thus, the 19F NMR spectrometric method is a useful technique to obtain the K p values of fluorinated drugs and thereby predict the theoretical lipid concentrations and prepare LNEs with high EE% values. PMID- 26863892 TI - Inferior alveolar nerve hemangioma. AB - A 14-year-old male presented with lower lip numbness and a slowly enlarging mandibular mass. Computed tomography demonstrated an expansile lesion centered in the marrow space of the left mandibular body, extending along the course of the inferior alveolar nerve (IAN), and expanding the mental foramen. Preoperative diagnosis was consistent with an IAN schwannoma. Surgical planning was performed using PROPLAN CMF software. The lesion was approached via a sagittal split osteotomy and excised en bloc with the IAN. Final pathology demonstrated a capillary hemangioma originating from the inferior alveolar nerve. Based on a detailed PubMed search, this is the first capillary hemangioma of the inferior alveolar nerve reported in the literature. Laryngoscope, 126:2168-2170, 2016. PMID- 26863893 TI - Efficacy of three different pulpotomy agents in primary molars: a randomized control trial. AB - AIM: To compare the clinical and radiographic efficacy of BiodentineTM , ProRoot(r) White Mineral Trioxide Aggregate (WMTA) and TempophoreTM as pulpotomy medicaments in the treatment of carious primary molars. METHODOLOGY: A parallel design, randomized controlled trial was developed. Patients above 3 years of age with carious primary teeth with vital pulps without spontaneous pain or history of swelling were included. Fifty-eight patients (82 teeth) with a mean age of 4.79 +/- 1.23 years were included. The teeth were randomized, blinded and allocated to one of the three groups (BiodentineTM , ProRoot(r) WMTA or TempophoreTM ) for pulpotomy treatment. All teeth were followed up clinically and radiographically (after 6, 12 and 18 months) by two blinded calibrated investigators. A generalized estimating equation (GEE), Wald chi-square test and an intention-to-treat analysis (ITT) with 'last carried forward' approach were performed using Statistical Package for Social Sciences v 21.0 (IBM Corp., Armonk, NK, USA). RESULTS: Forty-six patients and 69 teeth were available for follow-up after 18 months. Clinical success (radiographic success in parenthesis) was 95.24% (94.4%), 100% (90.9%) and 95.65% (82.4%) in the BiodentineTM , ProRoot(r) WMTA and TempophoreTM groups, respectively, but the difference was not significant. Pulp canal obliteration was significantly different amongst the experimental groups as the BiodentineTM group exhibited significantly more pulp canal obliteration when compared to the ProRoot(r) WMTA group at 6 months (P = 0.008) and 18 months (P = 0.003). CONCLUSIONS: After 18-month follow-up, there was no significant difference between BiodentineTM in comparison with ProRoot(r) WMTA or TempophoreTM . PMID- 26863895 TI - Nonenhanced magnetic resonance angiography (MRA) of the calf arteries at 3 Tesla: intraindividual comparison of 3D flow-dependent subtractive MRA and 2D flow independent non-subtractive MRA. AB - PURPOSE: To prospectively compare 3D flow-dependent subtractive MRA vs. 2D flow independent non-subtractive MRA for assessment of the calf arteries at 3 Tesla. METHODS: Forty-two patients with peripheral arterial occlusive disease underwent nonenhanced MRA of calf arteries at 3 Tesla with 3D flow-dependent subtractive MRA (fast spin echo sequence; 3D-FSE-MRA) and 2D flow-independent non-subtractive MRA (balanced steady-state-free-precession sequence; 2D-bSSFP-MRA). Moreover, all patients underwent contrast-enhanced MRA (CE-MRA) as standard-of-reference. Two readers performed a per-segment evaluation for image quality (4 = excellent to 0 = non-diagnostic) and severity of stenosis. RESULTS: Image quality scores of 2D bSSFP-MRA were significantly higher compared to 3D-FSE-MRA (medians across readers: 4 vs. 3; p < 0.0001) with lower rates of non-diagnostic vessel segments on 2D-bSSFP-MRA (reader 1: <1 % vs. 15 %; reader 2: 1 % vs. 29 %; p < 0.05). Diagnostic performance of 2D-bSSFP-MRA and 3D-FSE-MRA across readers showed sensitivities of 89 % (214/240) vs. 70 % (168/240), p = 0.0153; specificities: 91 % (840/926) vs. 63 % (585/926), p < 0.0001; and diagnostic accuracies of 90 % (1054/1166) vs. 65 % (753/1166), p < 0.0001. CONCLUSION: 2D flow-independent non subtractive MRA (2D-bSSFP-MRA) is a robust nonenhanced MRA technique for assessment of the calf arteries at 3 Tesla with significantly higher image quality and diagnostic accuracy compared to 3D flow-dependent subtractive MRA (3D FSE-MRA). KEY POINTS: * 2D flow-independent non-subtractive MRA (2D-bSSFP-MRA) is a robust NE-MRA technique at 3T * 2D-bSSFP-MRA outperforms 3D flow-dependent subtractive MRA (3D-FSE-MRA) as NE-MRA of calf arteries * 2D-bSSFP-MRA is a promising alternative to CE-MRA for calf PAOD evaluation. PMID- 26863894 TI - Athletes at High Altitude. AB - CONTEXT: Athletes at different skill levels perform strenuous physical activity at high altitude for a variety of reasons. Multiple team and endurance events are held at high altitude and may place athletes at increased risk for developing acute high altitude illness (AHAI). Training at high altitude has been a routine part of preparation for some of the high level athletes for a long time. There is a general belief that altitude training improves athletic performance for competitive and recreational athletes. EVIDENCE ACQUISITION: A review of relevant publications between 1980 and 2015 was completed using PubMed and Google Scholar. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: AHAI is a relatively uncommon and potentially serious condition among travelers to altitudes above 2500 m. The broad term AHAI includes several syndromes such as acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Athletes may be at higher risk for developing AHAI due to faster ascent and more vigorous exertion compared with nonathletes. Evidence regarding the effects of altitude training on athletic performance is weak. The natural live high, train low altitude training strategy may provide the best protocol for enhancing endurance performance in elite and subelite athletes. High altitude sports are generally safe for recreational athletes, but they should be aware of their individual risks. CONCLUSION: Individualized and appropriate acclimatization is an essential component of injury and illness prevention. PMID- 26863897 TI - Quantitative coronary CT angiography: absolute lumen sizing rather than %stenosis predicts hemodynamically relevant stenosis. AB - OBJECTIVE: To identify the most accurate quantitative coronary stenosis parameter by CTA for prediction of functional significant coronary stenosis resulting in coronary revascularization. METHODS: 160 consecutive patients were prospectively examined with CTA. Proximal coronary stenosis was quantified by minimal lumen area (MLA) and minimal lumen diameter (MLD), %area and %diameter stenosis. Lesion length (LL) was measured. The reference standard was invasive coronary angiography (ICA) (>70 % stenosis, FFR <0.8). RESULTS: 210 coronary segments were included (59 % positive). MLA of <=1.8 mm2 was identified as the optimal cut-off (c = 0.97, p < 0.001; 95 % CI 0.94-0.99) (sensitivity 90.9 %, specificity 89.3 %) for prediction of functional-relevant stenosis (for MLA >2.1 mm2 sensitivity was 100 %). The optimal cut-off for MLD was 1.2 mm (c = 0.92; p < 0.001; 95 % CI 0.88 95) (sensitivity 90.9, specificity 85.2) while %area and %diameter stenosis were less accurate (c = 0.89; 95 % CI 0.84-93, c = 0.87; 95 % CI 0.82-92, respectively, with thresholds at 73 % and 61 % stenosis). Accuracy for LL was c = 0.74 (95 % CI 0.67-81), and for LL/MLA and LL/MLD ratio c = 0.90 and c = 0.84. CONCLUSIONS: MLA <=1.8 mm2 and MLD <=1.2 mm are the most accurate cut-offs for prediction of haemodynamically significant stenosis by ICA, with a higher accuracy than relative % stenosis. KEY POINTS: * Quantitative coronary CT angiography is accurate for prediction of functional relevant stenosis. * Absolute lumen area and diameter rather than %stenosis predict functional relevance. * Lumen area <1.8 mm 2 and diameter <1.2 mm are the most accurate cut offs. * Quantitative parameters are helpful for decision-making in terms of patient management. PMID- 26863898 TI - An in vitro study on disinfection of titanium surfaces. AB - OBJECTIVE: The aim of this in vitro study was to evaluate the efficacy of different methods used for the decontamination of titanium surfaces previously infected with a Staphylococcus aureus biofilm. MATERIALS AND METHODS: S. aureus biofilms were grown on three different titanium surfaces (n = 114); polished, sandblasted large-grit acid-etched (SLA) and SLActive. The experimental groups were divided into six different disinfection modalities as follows: (i) rinsing with phosphate-buffered saline, (ii) rinsing with chlorhexidine digluconate 0.2% (CHX), (iii) application of photodynamic therapy (PDT), (iv) use of cotton pellet, (v) use of titanium brush (TiB) and (vi) the use of TiB and PDT. The decontamination effect of each modality was evaluated by microbial culture analysis and by scanning electron microscopy imaging. Two-way analysis of variance (ANOVA) and Bonferroni's post hoc comparisons were used to compare mean differences between colony-forming units per millilitre (CFU/ml) values, surfaces and treatments (P < 0.025). RESULTS: This study demonstrated that the combination protocol (TiB and PDT) was the most effective in reducing S. aureus (P < 0.025) on polished (2.0 * 103 CFU/Disc) and SLA surface (6.9 * 103 CFU/Disc). On the SLActive surface, the combination treatment was not significantly different to the TiB group (1.0 * 105 CFU/Disc) or the PDT group (2.0 * 105 CFU/Disc). CONCLUSION: The combined technique of TiB and PDT was shown to be an efficient method in reducing the number of S. aureus in both polished and rough titanium surfaces. These findings prompt further investigations in titanium decontamination techniques with a combination of TiB and PDT within a natural microcosm bacterial environment. PMID- 26863896 TI - Intravoxel incoherent motion MR imaging for breast lesions: comparison and correlation with pharmacokinetic evaluation from dynamic contrast-enhanced MR imaging. AB - OBJECTIVES: To compare diagnostic performance for breast lesions by quantitative parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and to explore whether correlations exist between these parameters. METHODS: IVIM and DCE MRI were performed on a 1.5-T MRI scanner in patients with suspicious breast lesions. Thirty-six breast cancers and 23 benign lesions were included in the study. Quantitative parameters from IVIM (D, f and D*) and DCE MRI (Ktrans, Kep, Ve and Vp) were calculated and compared between malignant and benign lesions. Spearman correlation test was used to evaluate correlations between them. RESULTS: D, f, D* from IVIM and Ktrans, Kep, Vp from DCE MRI were statistically different between breast cancers and benign lesions (p < 0.05, respectively) and D demonstrated the largest area under the receiver-operating characteristic curve (AUC = 0.917) and had the highest specificity (83 %). The f value was moderately statistically correlated with Vp (r = 0.692) and had a poor correlation with Ktrans (r = 0.456). CONCLUSIONS: IVIM MRI is useful in the differentiation of breast lesions. Significant correlations were found between perfusion-related parameters from IVIM and DCE MRI. IVIM may be a useful adjunctive tool to standard MRI in diagnosing breast cancer. KEY POINTS: * IVIM provided diffusion as well as perfusion information * IVIM could help differential diagnosis of breast lesions * Correlations were found between perfusion-related parameters from IVIM and DCE MRI. PMID- 26863899 TI - Can "true bifurcation lesion" actually be regarded as an independent risk factor of acute side branch occlusion after main vessel stenting?: A retrospective analysis of 1,200 consecutive bifurcation lesions in a single center. AB - OBJECTIVES: True bifurcation lesion (TBL) is conventionally considered as a risk factor for acute side branch (SB) occlusion when using a single-stent strategy to treat bifurcation lesions. The impact of TBLs on acute SB occlusion after main vessel (MV) stenting was investigated. METHODS: A total of 1,170 consecutive patients with 1,200 bifurcation lesions undergoing one-stent or provisional two stent techniques were studied. The TBLs were divided into two groups depending on their Medina classification. Multivariate logistic regression analysis was performed to identify independent predictors of acute SB occlusion. According to the median diameter of stenosis (DS) in the MV and the SB after pre-dilatation, the TBL group was divided into three subgroups: subgroup I (DS of both the MV and the SB =its respective median), and subgroup III (DS of both the MV and the SB >=their respective medians). The incidences of SB occlusion in these three subgroups were compared. RESULTS: Multivariate logistic regression analysis showed that TBL occurrence was not independently predictive of SB occlusion. Based on subgroup analysis, the incidence of SB occlusion in subgroup I (7.4%) was significantly lower than that in subgroup II (13.0%) and subgroup III (22.0%) (P = 0.025). However, there was no significant difference in the incidence of SB occlusion between TBL subgroup I (7.4%) and the non-TBL group (5.1%) (P = 0.53). CONCLUSIONS: TBL occurrence cannot be regarded as an independent predictor of acute SB occlusion after MV stenting. PMID- 26863900 TI - Dosing regimens, FVIII levels and estimated haemostatic protection with special focus on rFVIIIFc. AB - AIM: To use Pharmacokinetic (PK) simulations to illustrate potential differences in clinical outcomes between prophylaxis with conventional recombinant factor VIII (rFVIII) and rFVIIIFc, an extended half-life rFVIII covalently fused to the Fc domain of human IgG1. METHODS: Population PK estimates from 180 (rFVIIIFc) and 46 (rFVIII) severe haemophilia A patients were used to simulate FVIII activity over time at various rFVIIIFc dosing regimens compared to rFVIII 30 IU kg(-1) three times weekly in a typical adult patient. RESULTS: rFVIII dosed 3x30 IU kg( 1) weekly gave trough levels of 2.7, 2.8 and 0.7 IU dL(-1) , and time spent below 1, 3 and 5 IU dL(-1) of 0.2/1.2/2.3 days week(-1) . rFVIIIFc 2 x 45 IU kg(-1) gave higher troughs (4.4 and 1.7 IU dL(-1) ) and shorter time spent below 1, 3 and 5 IU dL(-1) (0/0.6/1.3 days week(-1) ), with same total factor consumption. rFVIIIFc 2 x 30 IU kg(-1) gave similar troughs (3.0 and 1.2 IU kg(-1) ) and time spent below 1, 3 and 5 IU dL(-1) (0/1.0/2.1 days week(-1) ), despite total factor consumption being reduced by one-third. The same dose and interval of rFVIIIFc (3 x 30 IU kg(-1) ) gave substantially higher troughs (7.8, 8.5 and 3.3 IU dL(-1) ) and markedly shorter time spent below 1, 3 and 5 IU dL(-1) (0/0/0.4 days week(-1) ). CONCLUSION: The lower clearance of rFVIIIFc compared to conventional rFVIII gives rFVIIIFc the potential of improved bleed prevention and reduced injection frequency at similar factor consumption. Although additional clinical data are required to confirm the conclusions, the simulations clearly show the potential of rFVIIIFc of increased flexibility to tailor treatment to the individual patient, and to advance the standard of care in haemophilia. PMID- 26863902 TI - Molecular biology and genetics of embryonic eyelid development. AB - The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-alpha, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/beta-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways. PMID- 26863901 TI - Membrane tubule formation by banana-shaped proteins with or without transient network structure. AB - In living cells, membrane morphology is regulated by various proteins. Many membrane reshaping proteins contain a Bin/Amphiphysin/Rvs (BAR) domain, which consists of a banana-shaped rod. The BAR domain bends the biomembrane along the rod axis and the features of this anisotropic bending have recently been studied. Here, we report on the role of the BAR protein rods in inducing membrane tubulation, using large-scale coarse-grained simulations. We reveal that a small spontaneous side curvature perpendicular to the rod can drastically alter the tubulation dynamics at high protein density, whereas no significant difference is obtained at low density. A percolated network is intermediately formed depending on the side curvature. This network suppresses tubule protrusion, leading to the slow formation of fewer tubules. Thus, the side curvature, which is generated by protein-protein and membrane-protein interactions, plays a significant role in tubulation dynamics. We also find that positive surface tensions and the vesicle membrane curvature can stabilize this network structure by suppressing the tubulation. PMID- 26863903 TI - Fabrication and design of metal nano-accordion structures using atomic layer deposition and interference lithography. AB - Metal nanostructures have attractive electrical and thermal properties as well as structural stability, and are important for applications in flexible conductors. In this study, we have developed a method to fabricate and control novel complex platinum nanostructures with accordion-like profile using atomic layer deposition on lithographically patterned polymer templates. The template removal process results in unique structural transformation of the nanostructure profile, which has been studied and modeled. Using different template duty cycles and aspect ratios, we have demonstrated a wide variety of cross-sectional profiles from wavy geometry to pipe array patterns. These complex thin metal nanostructures can find applications in flexible/stretchable electronics, photonics and nanofluidics. PMID- 26863904 TI - Sonography of the chest using linear-array versus sector transducers: Correlation with auscultation, chest radiography, and computed tomography. AB - PURPOSE: The primary purpose of our study was to compare the efficacies of two sonographic (US) probes, a high-frequency linear-array probe and a lower frequency phased-array sector probe in the diagnosis of basic thoracic pathologies. The secondary purpose was to compare the diagnostic performance of thoracic US with auscultation and chest radiography (CXR) using thoracic CT as a gold standard. METHODS: In total, 55 consecutive patients scheduled for thoracic CT were enrolled in this prospective study. Four pathologic entities were evaluated: pneumothorax, pleural effusion, consolidation, and interstitial syndrome. A portable US scanner was used with a 5-10-MHz linear-array probe and a 1-5-MHz phased-array sector probe. The first probe used was chosen randomly. US, CXR, and auscultation results were compared with the CT results. RESULTS: The linear-array probe had the highest performance in the identification of pneumothorax (83% sensitivity, 100% specificity, and 99% diagnostic accuracy) and pleural effusion (100% sensitivity, 97% specificity, and 98% diagnostic accuracy); the sector probe had the highest performance in the identification of consolidation (89% sensitivity, 100% specificity, and 95% diagnostic accuracy) and interstitial syndrome (94% sensitivity, 93% specificity, and 94% diagnostic accuracy). For all pathologies, the performance of US was superior to those of CXR and auscultation. CONCLUSIONS: The linear probe is superior to the sector probe for identifying pleural pathologies, whereas the sector probe is superior to the linear probe for identifying parenchymal pathologies. Thoracic US has better diagnostic performance than CXR and auscultation for the diagnosis of common pathologic conditions of the chest. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:383-389, 2016. PMID- 26863905 TI - Characterization of dermatopathology fellowship applicants: a 5-year single institution experience. AB - BACKGROUND: Although much data have been documented on the characteristics of medical school applicants for dermatology and pathology residency programs in the United States and select medical and surgical fellowship applicants through the National Residency Matching Program, little is known about the dermatopathology applicant demographics. METHODS: We examined a 5-year pool of dermatopathology fellowship applicants from a single institution (University of Arkansas for Medical Sciences) and compiled background profile data of the applicants to characterize an 'average dermatopathology fellow' applicant. RESULTS: A total of 229 applicants over a 5-year period were included in the assessment. The majority were of pathology background with medical school and residency training based in the southern United States. One-third of the applicants had original research publications, case reports or had given an oral or poster presentation in the field of dermatopathology. CONCLUSIONS: Knowledge regarding the average applicant statistics for a dermatopathology fellowship will allow prospective applicants to evaluate their own applications for strengths and weaknesses. This will also provide institutions information regarding anticipated statistics for a competitive applicant pool. PMID- 26863906 TI - Infantile Hemangiomas in Twins: A Prospective Cohort Study. AB - BACKGROUND: Twins have a higher-than-expected risk of infantile hemangiomas (IHs), but the exact reasons for this association are not clear. Comparing concordant and discordant twin pairs might help elucidate these factors and yield more information about IH risk factors. METHODS: A prospective cohort study of twin pairs from 12 pediatric dermatology centers in the United States, Canada, Argentina, and Spain was conducted. Information regarding maternal pregnancy history, family history of vascular birthmarks, zygosity (if known), and pregnancy-related information was collected. Information regarding twins (N = 202 sets) included birthweight, gestational age (GA), presence or absence of IHs, numbers and subtypes of IHs, presence of other birthmarks, and other medical morbidities. RESULTS: Two hundred two sets of twins were enrolled. Concordance for IH was present in 37% of twin pairs. Concordance for IH was inversely related to gestational age (GA), present in 42% of GA of 32 weeks or less, 36% of GA of 33 to 36 weeks, and 32% of GA of 37 weeks or more. Twins of GA of 34 weeks or less were more than two and a half times as likely to be concordant as those of GA of 35 weeks or more (odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.42-4.99; p < 0.01). In discordant twins, lower birthweight conferred a high risk of IH; of the 64 sets of twins with 10% or greater difference in weight, the smaller twin had IH in 62.5% (n = 40) of cases, versus 37.5% (n = 24) of cases in which the higher-birthweight twin was affected. Zygosity was reported in 188 twin sets (93%). Of these, 78% were dizygotic and 22% monozygotic. There was no statistically significant difference in rates of concordance between monozygotic twins (43%, 18/42) and dizygotic twins (36%, 52/146) (p = 0.50). In multivariate analysis comparing monozygotic and dizygotic twins, adjusting for effects of birthweight and sex, the likelihood of concordance for monozygotic was not appreciably higher than that for dizygotic twins (OR = 1.14, 95% CI = 0.52-2.49). Female sex also influenced concordance, confirming the effects of female sex on IH risk. The female-to-male ratio was 1.7:1 in the entire cohort and 1.9:1 in those with IH. Of the 61 concordant twin sets with known sex of both twins, 41% were female/female, 43% were female/male, and 16% were male/male. CONCLUSIONS: These findings suggest that the origin of IHs is multifactorial and that predisposing factors such as birthweight, sex, and GA may interact with one another such that a threshold is reached for clinical expression. PMID- 26863909 TI - Diet enriched with the Amazon fruit acai (Euterpe oleracea) prevents electrophysiological deficits and oxidative stress induced by methyl-mercury in the rat retina. AB - BACKGROUND: The protective effect of a diet supplemented by the Amazonian fruit Euterpe oleracea (EO) against methylmercury (MeHg) toxicity in rat retina was studied using electroretinography (ERG) and biochemical evaluation of oxidative stress. METHOD: Wistar rats were submitted to conventional diet or EO-enriched diet for 28 days. After that, each group received saline solution or 5 mg/kg/day of MeHg for 7 days. Full-field single flash, flash and flicker ERGs were evaluated in the following groups: control, EO, MeHg, and EO+MeHg. The amplitudes of the a-wave, b-wave, photopic negative response from rod and/or cone were measured by ERGs as well as the amplitudes and phases of the fundamental component of the sine-wave flicker ERG. Lipid peroxidation was determined by thiobarbituric acid reactive species. RESULTS: All ERG components had decreased amplitudes in the MeHg group when compared with controls. EO-enriched food had no effect on the non-intoxicated animals. The intoxicated animals and those that received the supplemented diet presented significant amplitude reductions of the cone b-wave and of the fundamental flicker component when compared with non intoxicated control. The protective effect of the diet on scotopic conditions was only observed for bright flashes eliciting a mixed rod and cone response. There was a significant increase of lipid peroxidation in the retina from animals exposed to MeHg and EO-supplemented diet was able to prevent MeHg-induced oxidative stress in retinal tissue. CONCLUSION: These findings open up perspectives for the use of diets supplemented with EO as a protective strategy against visual damage induced by MeHg. PMID- 26863910 TI - Assembling Quasi-enantiomeric Octahedral Complexes of Different Metals via Quasi racemate Crystallization. AB - Aiming at a general methodology for binary co-assembly of complexes of different metals through quasiracemate crystallization, the hexadentate ligand 1 comprised of the chiral bipyrrolidine core and two bipyridine peripheral arms is introduced. Ligand 1 was found to bind in a fully diastereoselective and uniform mode around Zn(II), Fe(II) and Cd(II) giving coordinatively inert octahedral "chiral-at-metal" complexes with the Delta4Lambda2/Lambda4 Delta2 wrapping mode. Equimolar mixtures of quasienantiomeric pairs of these complexes exhibited a clear tendency to pack as quasiracemates as was revealed from the crystallographic structures of [(R,R)-1-Zn](PF6)2/[(S,S)-1-Fe](PF6)2 and [(R,R)-1 Zn](PF6)2/[(S,S)-1-Cd](PF6)2, in an isomorphous fashion to that of the racemic compound [rac-1-Zn](PF6)2 in space group C2/c. PMID- 26863911 TI - Tofla virus: A newly identified Nairovirus of the Crimean-Congo hemorrhagic fever group isolated from ticks in Japan. AB - Ixodid ticks transmit several important viral pathogens. We isolated a new virus (Tofla virus: TFLV) from Heamaphysalis flava and Heamaphysalis formsensis in Japan. The full-genome sequences revealed that TFLV belonged to the genus Nairovirus, family Bunyaviridae. Phylogenetic analyses and neutralization tests suggested that TFLV is closely related to the Hazara virus and that it is classified into the Crimean-Congo hemorrhagic fever group. TFLV caused lethal infection in IFNAR KO mice. The TFLV-infected mice exhibited a gastrointestinal disorder, and positron emission tomography-computed tomography images showed a significant uptake of (18)F-fluorodeoxyglucose in the intestinal tract. TFLV was able to infect and propagate in cultured cells of African green monkey-derived Vero E6 cells and human-derived SK-N-SH, T98-G and HEK-293 cells. Although TFLV infections in humans and animals are currently unknown, our findings may provide clues to understand the potential infectivity and to develop of pre-emptive countermeasures against this new tick-borne Nairovirus. PMID- 26863912 TI - Updating Biodiversity Studies in Loricate Protists: The Case of the Tintinnids (Alveolata, Ciliophora, Spirotrichea). AB - Species determination is crucial in biodiversity research. In tintinnids, identification is based almost exclusively on the lorica, despite its frequent intraspecific variability and interspecific similarity. We suggest updated procedures for identification and, depending on the aim of the study, further steps to obtain morphological, molecular, and ecological data. Our goal is to help improving the collection of information (e.g. species re-/descriptions and DNA barcodes) that is essential for generating a natural tintinnid classification and a reliable reference for environmental surveys. These suggestions are broadly useful for protistologists because they exemplify data integration, quality/effort compromise, and the need for scientific collaborations. PMID- 26863913 TI - Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer. AB - In the United States, nearly 44,000 people are diagnosed with oral or pharyngeal cancer annually. The life expectancy for those who are diagnosed have a survival rate of 57% after five years. Among them, oral cancer can be classified as benign or malignant tumors and is diagnosed at several stages in the development: premalignant conditions, premalignant lesions, and malignant cancer. The early signs of oral cancer often go unnoticed by the individual and are often discovered during routine dental examinations. Early detection and treatment may help to increase patient survival rates. The most widely used treatments for oral cancer include surgery, radiation, and chemotherapy-alone or in combination. Preclinical and clinical evidence for the use of green tea, raspberry, asparagus, and cannabis extracts is discussed in this review. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission. Early detection and lifestyle changes, including the use of dietary supplements in at-risk populations, are critical steps in preventing and successfully treating oral cancer. The main evidence for supplement use is currently in cancer prevention rather than treatment. Further research, determination, and mechanism of action for bioactive compounds such as epigallocatechin, epicatechin-3 gallate, and Bowman-Birk inhibitor concentrate, through in vitro, in vivo, and clinical trials need to be completed to support the use of natural products and their effectiveness in preventative care and supporting therapeutic approaches. PMID- 26863914 TI - Incus footplate assembly: Indication and surgical outcome. AB - OBJECTIVES/HYPOTHESIS: To review surgical findings and hearing outcomes of incus footplate assembly (IFA) for the patients with conductive hearing loss due to missing stapes superstructure with a mobile stapes footplate. STUDY DESIGN: Retrospective case review and survey. METHODS: Pre- and postoperative audiometric data and intraoperative findings were reviewed. Postoperative air-bone gap (ABG) and ABG closure (postoperative air-conduction threshold-preoperative bone conduction threshold) were analyzed. RESULTS: The causes of missing stapes superstructure and conductive hearing loss were congenital ossicular anomaly (n = 5), chronic otitis media (n = 2), and congenital cholesteatoma (n = 1). The prosthesis was designed to fit between the medial side of the incus and stapes footplate and had a mean length of 3.6 +/- 0.5 mm. The mean pre- and postoperative ABG were 38.3 +/- 4.8 and 13.3 +/- 10.0 dB, respectively. The postoperative ABG at frequencies of 0.25, 0.5, 1.0, 2.0, 3.0, and 4.0 kHz were 20.0 +/- 15.4, 16.9 +/- 11.9, 16.3 +/- 10.3, 10.6 +/- 7.3, 12.9 +/- 14.0, and 23.1 +/- 16.2 dB, respectively. The mean ABG closure was 9.5 dB (range, -1.3~35.8 dB). Seven cases obtained the best results (mean ABG closure <=10 dB). In the remaining patient, the mean ABG closure was 9.5 dB until 6 months after surgery, but was 35.8 dB 1 year after surgery. CONCLUSIONS: IFA seems to be a reasonable surgical option in patients with missing the stapes superstructure, but with a mobile footplate in which the long process of incus is preserved. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2569-2573, 2016. PMID- 26863916 TI - Futile CPR is tantamount to assault. PMID- 26863915 TI - Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern. AB - Neoplasms with a myopericytomatous pattern represent a morphological spectrum of lesions encompassing myopericytoma of the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma and putative neoplasms reported as malignant myopericytoma. Lack of reproducible phenotypic and genetic features of malignant myopericytic neoplasms have prevented the establishment of myopericytic sarcoma as an acceptable diagnostic category. Following detection of a LMNA-NTRK1 gene fusion in an index case of paediatric haemangiopericytoma-like sarcoma by combined whole-genome and RNA sequencing, we identified three additional sarcomas harbouring NTRK1 gene fusions, termed 'spindle cell sarcoma, NOS with myo/haemangiopericytic growth pattern'. The patients were two children aged 11 months and 2 years and two adults aged 51 and 80 years. While the tumours of the adults were strikingly myopericytoma-like, but with clear-cut atypical features, the paediatric cases were more akin to infantile myofibromatosis/haemangiopericytoma. All cases contained numerous thick-walled dysplastic-like vessels with segmental or diffuse nodular myxohyaline myo-intimal proliferations of smooth muscle actin-positive cells, occasionally associated with thrombosis. Immunohistochemistry showed variable expression of smooth muscle actin and CD34, but other mesenchymal markers, including STAT6, were negative. This study showed a novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. Given the recent introduction of a novel therapeutic approach targeting NTRK fusion-positive neoplasms, recognition of this rare but likely under-reported sarcoma variant is strongly encouraged. PMID- 26863917 TI - Multimodality Imaging Strategies for the Assessment of Aortic Stenosis: Viewpoint of the Heart Valve Clinic International Database (HAVEC) Group. AB - Aortic stenosis is the most frequent valvular heart disease. In aortic stenosis, therapeutic decision essentially depends on symptomatic status, stenosis severity, and status of left ventricular systolic function. Surgical aortic valve replacement or transcatheter aortic valve implantation is the sole effective therapy in symptomatic patients with severe aortic stenosis, whereas the management of asymptomatic patients remains controversial and is mainly based on individual risk stratification. Imaging is fundamental for the initial diagnostic work-up, follow-up, and selection of the optimal timing and type of intervention. The present review provides specific recommendations for utilization of multimodality imaging to optimize risk stratification and therapeutic decision making processes in aortic stenosis. PMID- 26863918 TI - Redesigning Care for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: The "Shock Team". PMID- 26863919 TI - Pharmacological treatment of HIV-associated pulmonary hypertension. AB - Pulmonary arterial hypertension (PAH) is a rare but severe disease that results from chronic obstruction of small pulmonary arteries, leading to right ventricular failure and, ultimately, death. One established risk factor for the development of PAH is HIV infection. The presence of PAH is an independent risk factor for mortality in HIV-infected patients. This article will focus on HIV associated PAH (HIV-PAH) with special considerations to the available treatments. With the approval of the soluble guanylate cyclase stimulator riociguat, a new drug class has become available in addition to the already existing prostanoids, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. Guidelines for the treatment of idiopathic PAH and guidelines for antiretroviral therapy should be followed for the treatment of HIV-PAH. PMID- 26863920 TI - Progression of nonmotor symptoms in subgroups of patients with non-dopamine deficient Parkinsonism. AB - BACKGROUND: Ten to fifteen percent of Parkinson's disease (PD) patients recruited to clinical trials have scans without evidence of dopaminergic deficit, whose presence represents a heterogeneous patient population. METHODS: A cohort of 41 patients with parkinsonism and scans without evidence of dopaminergic deficit at baseline, were subdivided into groups according to their final clinical diagnoses and nigrostriatal dopamine function assessed after 2 years of study. At follow up, 23 patients had clinically probable PD or unclassified parkinsonism with normal nigrostriatal dopamine imaging ("true" scans without evidence of dopaminergic deficit), nine were diagnosed with another tremulous condition, five had psychogenic parkinsonism, and four had phenoconverted to PD with reduced nigrostriatal dopamine function. We analyzed nonmotor symptoms at baseline and follow-up in subgroups of patients with scans without evidence of dopaminergic deficit in comparison with a random sample of 62 PD patients and 195 healthy controls (HCs). All patients were enrolled in the Parkinson's Progressive Marker's Initiative. RESULTS: Patients who had true scans without evidence of dopaminergic deficit had more severe rapid eye movement sleep disorder, depression, anxiety, and autonomic dysfunction than HCs in addition to more frequent depressive symptoms and worse cardiovascular dysfunction than patients with PD (P = 0.038, P = 0.047, respectively). Patients with true scans without evidence of dopaminergic deficit had normal olfaction that was significantly better than that of patients with PD (P < 0.001). Subgroup analysis of the cohort with scans without evidence of dopaminergic deficit revealed that all patients shared similar nonmotor features irrespective of their final clinical diagnoses. Follow-up of subject groups showed stable nonmotor symptoms over 2 years of study. CONCLUSIONS: At an early symptomatic stage, patients with scans without evidence of dopaminergic deficit and long-standing parkinsonism exhibit nonmotor features that differ from those of patients with PD on mood and cardiovascular and olfactory function, but remain similar to patients with scans without evidence of dopaminergic deficit with alternative final diagnoses. PMID- 26863921 TI - Structural characterization of the N-linked pentasaccharide decorating glycoproteins of the halophilic archaeon Haloferax volcanii. AB - N-Glycosylation is a post-translational modification performed in all three domains of life. In the halophilic archaea Haloferax volcanii, glycoproteins such as the S-layer glycoprotein are modified by an N-linked pentasaccharide assembled by a series of Agl (archaeal glycosylation) proteins. In the present study, mass spectrometry (MS) and nuclear magnetic resonance spectroscopy were used to define the structure of this glycan attached to at least four of the seven putative S layer glycoprotein N-glycosylation sites, namely Asn-13, Asn-83, Asn-274 and Asn 279. Such approaches detected a trisaccharide corresponding to glucuronic acid (GlcA)-beta1,4-GlcA-beta1,4-glucose-beta1-Asn, a tetrasaccharide corresponding to methyl-O-4-GlcA-beta-1,4-galacturonic acid-alpha1,4-GlcA-beta1,4-glucose-beta1 Asn, and a pentasaccharide corresponding to hexose-1,2-[methyl-O-4-]GlcA-beta-1,4 galacturonic acid-alpha1,4-GlcA-beta1,4-glucose-beta1-Asn, with previous MS and radiolabeling experiments showing the hexose at the non-reducing end of the pentasaccharide to be mannose. The present analysis thus corrects the earlier assignment of the penultimate sugar as a methyl ester of a hexuronic acid, instead revealing this sugar to be a methylated GlcA. The assignments made here are in good agreement with what was already known of the Hfx. volcanii N glycosylation pathway from previous genetic and biochemical efforts while providing new insight into the process. PMID- 26863924 TI - Focal Adhesion Kinase Signaling Mediated the Enhancement of Osteogenesis of Human Mesenchymal Stem Cells Induced by Extracorporeal Shockwave. AB - Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm(2)) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins. PMID- 26863923 TI - Drugging Membrane Protein Interactions. AB - The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind cells to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally "undruggable" regions of membrane proteins, enabling modulation of protein-protein, protein-lipid, and protein-nucleic acid interactions. In this review, we survey the state of the art of high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets. PMID- 26863925 TI - Cranio-facial remodeling in domestic dogs is associated with changes in larynx position. AB - The hyo-laryngeal complex is a multi-segmented structure integrating the oral and pharyngeal cavities and thus a variety of critical functions related to airway control, feeding, and vocal communication. Currently, we lack a complete understanding of how the hyoid complex, and the functions it mediates, can also be affected by changes in surrounding cranio-facial dimensions. Here, we explore these relationships in a breed of domestic dog, the Portuguese Water Dog, which is characterized by strong cranio-facial variation. We used radiographic images of the upper body and head of 55 adult males and 51 adult females to obtain detailed measures of cranio-facial variation and hyoid anatomy. Principal components analysis revealed multiple orthogonal dimensions of cranio-facial variation, some of which were associated with significant differences in larynx position: the larynx occupied a more descended position in individuals with shorter, broader faces than in those with longer, narrower faces. We then tested the possibility that caudal displacement of the larynx in brachycephalic individuals might reflect a degree of tongue crowding resulting from facial shortening and reduction of oral and pharyngeal spaces. A cadaver sample was used to obtain detailed measurements of constituent bones of the hyoid skeleton and of the tongue body, and their relationships to cranio-facial size and shape and overall body size supported the tongue-crowding hypothesis. Considering the presence of descended larynges in numerous mammalian taxa, our findings establish an important precedent for the possibility that laryngeal descent can be initiated, and even sustained, in part in response to remodeling of the face and cranium for selective pressures unrelated to vocal production. These integrated changes could also have been involved in hominin evolution, where the different laryngeal positions in modern humans compared with nonhuman primates have been traditionally linked to the evolution of speech but which are likely to be multifactorial. PMID- 26863927 TI - Investigational ErbB-2 tyrosine kinase inhibitors for the treatment of breast cancer. AB - INTRODUCTION: ErbB2 overexpression and/or gene amplification is present in 20% of all breast cancers and characterizes an aggressive form of this disease. Despite the availability of several active drugs that have yielded substantial survival improvements, most patients with ErbB2-positive metastatic disease will develop tumor progression, either because of primary or acquired resistance. Therefore, research has focused on drugs that can more efficiently interfere with ErbB2 and with other members of the epidermal growth factor receptor family. AREAS COVERED: This review focuses on those investigational drugs that inhibit ErbB2 tyrosine kinase activity (TKIs) for treating breast cancer. EXPERT OPINION: ErbB-targeting TKIs show encouraging activity in patients with ErbB-positive tumors that are resistant to conventional ErbB-therapies (mostly trastuzumab), confirming pre clinical observations. Efficient interference with the ErbB-network signaling implies also a potential use in ErbB2-normal tumors, where the phenotype is sustained by ErbB-aberrant signaling. Finally, early data suggests that ErbB targeting TKIs could be active in treating patients with activating ErbB2 mutations. Ongoing and future research efforts should elucidate what is, according to the peculiarities of these compounds, their positioning in the treatment of women with breast cancer. PMID- 26863926 TI - Health behaviours and fear of cancer recurrence in 10 969 colorectal cancer (CRC) patients. AB - BACKGROUND: This study aimed to examine whether fear of cancer recurrence (FCR) was related to two important health behaviours (physical activity and smoking) in a large sample of colorectal cancer patients. METHODS: Ten thousand nine hundred sixty nine patients, diagnosed in 2010-11, and in remission in 2013, completed the 'Living with and Beyond Colorectal Cancer' survey. The survey included purpose-designed questions on fear of recurrence ('I have fear about my cancer coming back'), demographics, treatment and health variables. Physical activity (PA) was recorded as number of days per week doing at least 30 min of brisk activity, and smoking status was reported. RESULTS: Fifty per cent of respondents reported fear of their cancer returning. More women than men ((Odds Ratio; (OR) 1.58; 95% confidence interval (CI) 1.46, 1.71)) more younger than older patients (OR 2.53; CI 2.33, 2.74) and slightly more patients from deprived areas (OR 1.14, 1.05, 1.23) reported FCR. Independently of demographics and treatment, compared with those meeting the PA guidelines, those who were doing only 'some' (OR 1.22; CI 1.11, 1.35) or 'no' PA (OR 1.28; CI 1.15, 1.42) reported higher FCR. Compared with non-smokers, more current smokers reported fear (OR 1.34, CI 1.10, 1.58) and slightly more ex-smokers (OR 1.11; CI 1.04, 1.21). CONCLUSIONS: This cross sectional study provided novel data showing that colorectal cancer survivors with poorer health behaviours (those with lower activity levels and those who smoked) were more likely to experience FCR. Future research should replicate findings using detailed measures of fear, objective measures of health behaviours and identify directions of associations. (c) 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd. PMID- 26863928 TI - Synthetic Control of the Excited-State Dynamics and Circularly Polarized Luminescence of Fluorescent "Push-Pull" Tetrathia[9]helicenes. AB - A series of fluorescent "push-pull" tetrathia[9]helicenes based on quinoxaline (acceptor) fused with tetrathia[9]helicene (donor) derivatives was synthesized for control of the excited-state dynamics and circularly polarized luminescence (CPL) properties. In this work, introduction of a quinoxaline onto the tetrathia[9]helicene skeleton induced the "push-pull" character, which was enhanced by further introduction of an electron-releasing Me2 N group or an electron-withdrawing NC group onto the quinoxaline unit (denoted as Me2 N-QTTH and NC-QTTH, respectively). These trends were successfully discussed in terms of by electrochemical measurements and density functional theory (DFT) calculations. As a consequence, significant enhancements in the fluorescence quantum yields (PhiFL ) were achieved. In particular, the maximum PhiFL of Me2 N-QTTH was 0.43 in benzene (NC-QTTH: PhiFL =0.30), which is more than 20 times larger than that of a pristine tetrathia[9]helicene (denoted as TTH; PhiFL =0.02). These enhancements were also explained by kinetic discussion of the excited-state dynamics such as fluorescence and intersystem crossing (ISC) pathways. Such significant enhancements of the PhiFL values thus enabled us to show the excellent CPL properties. The value of anisotropy factor gCPL (normalized difference in emission of right-handed and left-handed circularly polarized light) was estimated to be 3.0 * 10(-3) for NC-QTTH. PMID- 26863922 TI - The Lymphatic System in Disease Processes and Cancer Progression. AB - Advances in our understanding of the structure and function of the lymphatic system have made it possible to identify its role in a variety of disease processes. Because it is involved not only in fluid homeostasis but also in immune cell trafficking, the lymphatic system can mediate and ultimately alter immune responses. Our rapidly increasing knowledge of the molecular control of the lymphatic system will inevitably lead to new and effective therapies for patients with lymphatic dysfunction. In this review, we discuss the molecular and physiological control of lymphatic vessel function and explore how the lymphatic system contributes to many disease processes, including cancer and lymphedema. PMID- 26863930 TI - Right-Left Differences in Knee Extension Stiffness for the Normal Rat Knee: In Vitro Measurements Using a New Testing Apparatus. AB - Knee stiffness following joint injury or immobilization is a common clinical problem, and the rat has been used as a model for studies related to joint stiffness and limitation of motion. Knee stiffness measurements have been reported for the anesthetized rat, but it is difficult to separate the contributions of muscular and ligamentous restraints to the recorded values. in vitro testing of isolated rat knees devoid of musculature allows measurement of joint structural properties alone. In order to measure the effects of therapeutic or surgical interventions designed to alter joint stiffness, the opposite extremity is often used as a control. However, right-left stiffness differences for the normal rat knee have not been reported in the literature. If stiffness changes observed for a treatment group are within the normal right-left variation, validity of the results could be questioned. The objectives of this study were to utilize a new testing apparatus to measure right-left stiffness differences during knee extension in a population of normal rat knees and to document repeatability of the stiffness measurements on successive testing days. Moment versus rotation curves were recorded for 15 right-left pairs of normal rat knees on three consecutive days, with overnight specimen storage in a refrigerator. Each knee was subjected to ten loading-unloading cycles, with the last loading curve used for analysis. Angular rotation (AR), defined here as the change in flexion-extension angle from a specified applied joint moment, is commonly used as a measure of overall joint stiffness. For these tests, ARs were measured from the recorded test curves with a maximum applied extension moment of 100 g cm. Mean rotations for testing days 2 and 3 were 0.81-1.25 deg lower (p < 0.001) than for day 1, but were not significantly different from each other. For each testing day, mean rotations for right knees were 1.12-1.30 deg greater (p < 0.001) than left knees. These right-left stiffness differences should be considered when interpreting the results of knee treatment studies designed to alter knee stiffness when using the opposite extremity as a control. PMID- 26863929 TI - Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates. AB - Since the iron-age and throughout the industrial age, humans have been exposed to iron oxides. Here, we review the evidence from epidemiology, toxicology, and lung bioavailability as to whether iron oxides are likely to act as human lung carcinogens. Current evidence suggests that observed lung tumors in rats result from a generic particle overload effect and local inflammation that is rat specific under the dosing conditions of intratracheal instillation. This mode of action therefore, is not relevant to human exposure. However, there are emerging differences seen in vitro, in cell uptake and cell bioavailability between "bulk" iron oxides and "nano" iron oxides. "Bulk" particulates, as defined here, are those where greater than 70% are >100 nm in diameter. Similarly, "nano" iron oxides are defined in this context as particulates where the majority, usually >95% for pure engineered forms of primary particulates (not agglomerates), fall in the range 1-100 nm in diameter. From the weight of scientific evidence, "bulk" iron oxides are not genotoxic/mutagenic. Recent evidence for "nano" iron oxide is conflicting regarding genotoxic potential, albeit genotoxicity was not observed in an in vivo acute oral dose study, and "nano" iron oxides are considered safe and are being investigated for biomedical uses; there is no specific in vivo genotoxicity study on "nano" iron oxides via inhalation. Some evidence is available that suggests, hypothetically due to the larger surface area of "nano" iron oxide particulates, that toxicity could be exerted via the generation of reactive oxygen species (ROS) in the cell. However, the potential for ROS generation as a basis for explaining rodent tumorigenicity is only apparent if free iron from intracellular "nano" scale iron oxide becomes bioavailable at significant levels inside the cell. This would not be expected from "bulk" iron oxide particulates. Furthermore, human epidemiological evidence from a number of studies suggests that iron oxide is not a human carcinogen, and therefore, based upon the complete weight of evidence, we conclude that "bulk" iron oxides are not human carcinogens. PMID- 26863931 TI - Gene expression analyses of vitellogenin, choriogenin and estrogen receptor subtypes in the livers of male medaka (Oryzias latipes) exposed to equine estrogens. AB - In the present study, we investigated transcriptional profiles of estrogen responsive genes, such as vitellogenins (Vtg1 and Vtg2), choriogenins (ChgL and ChgH) and estrogen receptor subtypes (ERalpha, ERbeta1, and ERbeta2), in the liver of male medaka fish (Oryzias latipes) that were exposed to six equine estrogens (1-300 ng l(-1) ) for 3 days. Our quantitative reverse transcription polymerase chain reaction (RT-PCR) analyses revealed that the expression levels of hepatic Vtg, Chg and ERalpha genes in male medaka responded to various types and concentrations of equine estrogens. The estrogenic potentials of the tested chemicals were in the order of equilin > 17beta-estradiol > equilenin > 17beta dihydroequilin > 17beta-dihydroequilenin > 17alpha-dihydroequilin > 17alpha dihydroequilenin, showing the higher estrogenic potential of equilin than that of 17beta-estradiol. Our results also showed that the estrogenicities of 17beta dihydroequilin and 17beta-dihydroequilenin were more potent than that of 17alpha dihydroequilin and 17alpha-dihydroequilenin. Furthermore, in gene expression analyses of hepatic ER subtypes, observations were made to note that 17beta estradiol and equilin induced ERalpha transcription in male medaka, and the ERalpha transcription level had significantly positive correlations with the expression of Vtg and Chg genes. In contrast, in the same 17beta-estradiol and equilin treatment groups, it was shown that the transcription levels of hepatic ERbeta1 and/or ERbeta2 had significantly negative correlations with the expression of Vtg and Chg genes. These results suggested some potential involvement of the ER subtypes in the regulation of Vtg and Chg gene expressions in the liver. This is the first report describing the comprehensive analyses of in vivo estrogenicity of the equine estrogens in male medaka. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26863932 TI - Serum paraoxonase level and paraoxonase polymorphism in patients with acromegaly. AB - BACKGROUND: Acromegalic patients have increased cardiometabolic risk factors due to an elevation of growth hormone (GH) levels. Human serum paraoxonase (PON), a high-density lipoprotein (HDL)-related enzyme, is one of the major bioscavengers and decreases the oxidation of low-density lipoprotein (LDL), a key regulator in the pathogenesis of atherosclerosis. In this study, we investigated a potential relationship between serum PON levels or PON polymorphisms and acromegaly. METHODS: A total of 48 acromegalic patients and 44 healthy controls were included in this study. Serum GH levels, insulin-like growth factor-1 levels and lipid profiles were measured. Serum PON levels, as well as PON 1 L55M and Q192R gene polymorphisms, were examined. RESULTS: No significant differences were found in terms of age, gender, presence of diabetes, serum LDL cholesterol (LDL-C), HDL-C, or triglyceride levels between the case and control groups (P > 0.05). A statistically significant difference was found in serum PON levels between the cases and controls (P = 0.007). The median serum PON level was 101 +/- 63.36 U/l in the case group and 63 +/- 60.50 U/l in the control group. There was a significant correlation between serum PON levels and IGF-1 levels (P = 0.004, r = 0.319); however, no significant differences were found in PON1 L55M and PON Q192R polymorphisms between the patients and controls (P = 0.607 and P = 0.308, respectively). In addition, no significant differences were found in serum PON levels in acromegalic patients who were and were not in remission (P = 0.385), nor between those with PON1 L55M and Q192R polymorphisms (P = 0.161 and P = 0.336, respectively). CONCLUSIONS: Elevated serum PON levels were detected in acromegalic patients, independently of their remission status. This suggests protective effects for cardiometabolic risk parameters. PMID- 26863933 TI - Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice. AB - Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-alpha, IL 1beta, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity. PMID- 26863934 TI - Toward Scalable Fabrication of Hierarchical Silica Capsules with Integrated Micro , Meso-, and Macropores. AB - Hierarchical porous structures are ubiquitous in biological organisms and inorganic systems. Although such structures have been replicated, designed, and fabricated, they are often inferior to naturally occurring analogues. Apart from the complexity and multiple functionalities developed by the biological systems, the controllable and scalable production of hierarchically porous structures and building blocks remains a technological challenge. Herein, a facile and scalable approach is developed to fabricate hierarchical hollow spheres with integrated micro-, meso-, and macropores ranging from 1 nm to 100 MUm (spanning five orders of magnitude). (Macro)molecules, micro-rods (which play a key role for the creation of robust capsules), and emulsion droplets have been successfully employed as multiple length scale templates, allowing the creation of hierarchical porous macrospheres. Thanks to their specific mechanical strength, these hierarchical porous spheres could be incorporated and assembled as higher level building blocks in various novel materials. PMID- 26863935 TI - The Total Synthesis of (+/-)-Naupliolide: A Tetracyclic Sesquiterpene Lactone. AB - The first total synthesis of (+/-)-naupliolide has been achieved. The synthetic method includes a Simmons-Smith cyclopropanation of an allyl alcohol, diastereoselective cleavage of a benzylidene acetal group, radical cyclization of an aldehyde with a cyclopropane ring, and construction of an eight-membered ring by ring-closing metathesis. PMID- 26863936 TI - Transcontinental dispersal, ecological opportunity and origins of an adaptive radiation in the Neotropical catfish genus Hypostomus (Siluriformes: Loricariidae). AB - Ecological opportunity is often proposed as a driver of accelerated diversification, but evidence has been largely derived from either contemporary island radiations or the fossil record. Here, we investigate the potential influence of ecological opportunity on a transcontinental radiation of South American freshwater fishes. We generate a species-dense, time-calibrated molecular phylogeny for the suckermouth armored catfish subfamily Hypostominae, with a focus on the species-rich and geographically widespread genus Hypostomus. We use the resulting chronogram to estimate ancestral geographical ranges, infer historical rates of cladogenesis and diversification in habitat and body size and shape, and test the hypothesis that invasions of previously unoccupied river drainages accelerated evolution and contributed to adaptive radiation. Both the subfamily Hypostominae and the included genus Hypostomus originated in the Amazon/Orinoco ecoregion. Hypostomus subsequently dispersed throughout tropical South America east of the Andes Mountains. Consequent to invasion of the peripheral, low-diversity Parana River basin in southeastern Brazil approximately 12.5 Mya, Parana lineages of Hypostomus, experienced increased rates of cladogenesis and ecological and morphological diversification. Contemporary lineages of Parana Hypostomus are less species rich but more phenotypically diverse than their congeners elsewhere. Accelerated speciation and morphological diversification rates within Parana basin Hypostomus are consistent with adaptive radiation. The geographical remoteness of the Parana River basin, its recent history of marine incursion, and its continuing exclusion of many species that are widespread in other tropical South American rivers suggest that ecological opportunity played an important role in facilitating the observed accelerations in diversification. PMID- 26863937 TI - The ring residue proline 8 is crucial for the thermal stability of the lasso peptide caulosegnin II. AB - Lasso peptides are fascinating natural products with a unique structural fold that can exhibit tremendous thermal stability. Here, we investigate factors responsible for the thermal stability of caulosegnin II. By employing X-ray crystallography, mutational analysis and molecular dynamics simulations, the ring residue proline 8 was proven to be crucial for thermal stability. PMID- 26863938 TI - Washout rate in rat brain irradiated by a (11)C beam after acetazolamide loading using a small single-ring OpenPET prototype. AB - In dose verification techniques of particle therapies based on in-beam positron emission tomography (PET), the causes of washout of positron emitters by physiological effects should be clarified to correct washout for accurate verification. As well, the quantitative washout rate has a potential usefulness as a diagnostic index which should be explored. Therefore, we measured washout rates of rat brain after vasodilator acetazolamide loading to investigate the possible effects of blood flow on washout. Six rat brains were irradiated by a radioisotope (11)C beam and time activity curves on the whole brains were obtained with a small single-ring OpenPET prototype. Then, washout rates were calculated with the Mizuno model, where two washout rates (k 2m and k 2s ) were assumed, and a two-compartment model including efflux from tissue to blood (k 2) and influx (k 3) and efflux (k 4) between the two tissue compartments. Before the irradiations, we used laser-Doppler flowmetry to confirm that acetazolamide increased cerebral blood flow (CBF) of a rat. We compared means of k 2m , k 2s and k 2, k 3 and k 4 without acetazolamide loading (Rest) and with acetazolamide loading (ACZ). For all k values, ACZ values were lower than Rest values. In other words, though CBF increased, washout rates were decreased. This may be attributed to the implanted (11)C reacting to form (11)CO2. Because acetazolamide increased the concentration of CO2 in brain, suppressed diffusion of (11)CO2 and decomposition of (11)CO2 into ions were prevented. PMID- 26863939 TI - A novel solid state photocatalyst for living radical polymerization under UV irradiation. AB - This study presents the development of a novel solid state photocatalyst for the photoinduced controlled radical polymerization of methacrylates under mild UV irradiation (lambdamax ~ 365 nm) in the absence of conventional photoinitiators, metal-catalysts or dye sensitizers. The photocatalyst design was based on our previous finding that organic amines can act in a synergistic photochemical reaction with thiocarbonylthio compounds to afford well controlled polymethacrylates under UV irradiation. Therefore, in the current contribution an amine-rich polymer was covalently grafted onto a solid substrate, thus creating a heterogeneous catalyst that would allow for facile removal, recovery and recyclability when employed for such photopolymerization reactions. Importantly, the polymethacrylates synthesized using the solid state photocatalyst (ssPC) show similarly excellent chemical and structural integrity as those catalysed by free amines. Moreover, the ssPC could be readily recovered and re-used, with multiple cycles of polymerization showing minimal effect on the integrity of the catalyst. Finally, the ssPC was employed in various photo-"click" reactions, permitting high yielding conjugations under photochemical control. PMID- 26863940 TI - The plant hopper Issus coleoptratus can detoxify phloem sap saponins including the degradation of the terpene core. AB - Issus coleoptratus is a small plant hopper which mainly feeds on the phloem sap from ivy. Although all parts of ivy are poisonous as the plant contains saponins, especially hederasaponins, I. coleoptratus can cope with the poison. In contrast to other animals like the stick insect Carausius morosus which accumulates saponins in its body, I. coleoptratus can degrade and disintegrate not only the saponins but even the genines, i.e. the triterpene core of the substances. This is perhaps made possible by a specialised midgut and/or the salivary glands. When the glands and the gut are dissected and added to saponins in solution, the saponins, including the genines, are degraded ex vivo. PMID- 26863942 TI - Analysis of Dog Adoption Success and Failure Using Surveys With Vignettes. AB - Adoption success of dogs who serve as companion animals was analyzed via surveys with vignettes. The researchers administered surveys with vignettes to animal shelter employees, veterinarians, and other animal-care professionals in Eastern North Carolina. Logistic and linear regression analyses were used to identify variables that were perceived to influence adoption success. Dog size, personality, behavior, and level of obedience training were found to be significant perceived influencers of adoption success. Prospective caregiver characteristics such as gender and level of activity were shown to be perceived as significant. Guidance on the practical use of the logistic regression model is provided, and limitations of the study are described. PMID- 26863941 TI - Prickle isoforms control the direction of tissue polarity by microtubule independent and dependent mechanisms. AB - Planar cell polarity signaling directs the polarization of cells within the plane of many epithelia. While these tissues exhibit asymmetric localization of a set of core module proteins, in Drosophila, more than one mechanism links the direction of core module polarization to the tissue axes. One signaling system establishes a polarity bias in the parallel, apical microtubules upon which vesicles containing core proteins traffic. Swapping expression of the differentially expressed Prickle isoforms, Prickle and Spiny-legs, reverses the direction of core module polarization. Studies in the proximal wing and the anterior abdomen indicated that this results from their differential control of microtubule polarity. Prickle and Spiny-legs also control the direction of polarization in the distal wing (D-wing) and the posterior abdomen (P-abd). We report here that this occurs without affecting microtubule polarity in these tissues. The direction of polarity in the D-wing is therefore likely determined by a novel mechanism independent of microtubule polarity. In the P-abd, Prickle and Spiny-legs interpret at least two directional cues through a microtubule polarity-independent mechanism. PMID- 26863943 TI - Benefits of sharing. PMID- 26863944 TI - A good precedent. PMID- 26863945 TI - Outside the bubble. PMID- 26863946 TI - Change the system to halt harassment. PMID- 26863958 TI - Tasmanian bushfires threaten iconic ancient forests. PMID- 26863959 TI - How should science funders deal with sexual harassers? PMID- 26863960 TI - High stakes as Japanese space observatory prepares for launch. PMID- 26863961 TI - Biotech giant publishes failures to confirm high-profile science. PMID- 26863962 TI - US panel greenlights creation of male 'three-person' embryos. PMID- 26863963 TI - Proving Zika link to birth defects poses huge challenge. PMID- 26863964 TI - Corrections. PMID- 26863965 TI - The chips are down for Moore's law. PMID- 26863966 TI - Does it take too long to publish research? PMID- 26863967 TI - Emissions reduction: Scrutinize CO2 removal methods. PMID- 26863972 TI - Climate change: Metrics needed to track adaptation. PMID- 26863968 TI - Global warming: Shareholders must vote for climate-change mitigation. PMID- 26863973 TI - Social sciences: IPBES disciplinary gaps still gaping. PMID- 26863974 TI - European Union: More to fisheries than catch limits. PMID- 26863975 TI - Surgical techniques: When brain bullets met crowdfunding. PMID- 26863976 TI - Plasma physics: Compact coupling for a two-stage accelerator. PMID- 26863977 TI - Ebola: Sequencing on the ground. PMID- 26863978 TI - Crystallography: Resolution beyond the diffraction limit. PMID- 26863979 TI - Astrophysics: Exoplanets hidden in the gaps. PMID- 26863981 TI - New geological and palaeontological age constraint for the gorilla-human lineage split. AB - The palaeobiological record of 12 million to 7 million years ago (Ma) is crucial to the elucidation of African ape and human origins, but few fossil assemblages of this period have been reported from sub-Saharan Africa. Since the 1970s, the Chorora Formation, Ethiopia, has been widely considered to contain ~10.5 million year (Myr) old mammalian fossils. More recently, Chororapithecus abyssinicus, a probable primitive member of the gorilla clade, was discovered from the formation. Here we report new field observations and geochemical, magnetostratigraphic and radioisotopic results that securely place the Chorora Formation sediments to between ~9 and ~7 Ma. The C. abyssinicus fossils are ~8.0 Myr old, forming a revised age constraint of the human-gorilla split. Other Chorora fossils range in age from ~8.5 to 7 Ma and comprise the first sub-Saharan mammalian assemblage that spans this period. These fossils suggest indigenous African evolution of multiple mammalian lineages/groups between 10 and 7 Ma, including a possible ancestral-descendent relationship between the ~9.8 Myr old Nakalipithecus nakayamai and C. abyssinicus. The new chronology and fossils suggest that faunal provinciality between eastern Africa and Eurasia had intensified by ~9 Ma, with decreased faunal interchange thereafter. The Chorora evidence supports the hypothesis of in situ African evolution of the Gorilla-Pan human clade, and is concordant with the deeper divergence estimates of humans and great apes based on lower mutation rates of ~0.5 * 10(-9) per site per year (refs 13 - 15). PMID- 26863980 TI - Macromolecular diffractive imaging using imperfect crystals. AB - The three-dimensional structures of macromolecules and their complexes are mainly elucidated by X-ray protein crystallography. A major limitation of this method is access to high-quality crystals, which is necessary to ensure X-ray diffraction extends to sufficiently large scattering angles and hence yields information of sufficiently high resolution with which to solve the crystal structure. The observation that crystals with reduced unit-cell volumes and tighter macromolecular packing often produce higher-resolution Bragg peaks suggests that crystallographic resolution for some macromolecules may be limited not by their heterogeneity, but by a deviation of strict positional ordering of the crystalline lattice. Such displacements of molecules from the ideal lattice give rise to a continuous diffraction pattern that is equal to the incoherent sum of diffraction from rigid individual molecular complexes aligned along several discrete crystallographic orientations and that, consequently, contains more information than Bragg peaks alone. Although such continuous diffraction patterns have long been observed--and are of interest as a source of information about the dynamics of proteins--they have not been used for structure determination. Here we show for crystals of the integral membrane protein complex photosystem II that lattice disorder increases the information content and the resolution of the diffraction pattern well beyond the 4.5-angstrom limit of measurable Bragg peaks, which allows us to phase the pattern directly. Using the molecular envelope conventionally determined at 4.5 angstroms as a constraint, we obtain a static image of the photosystem II dimer at a resolution of 3.5 angstroms. This result shows that continuous diffraction can be used to overcome what have long been supposed to be the resolution limits of macromolecular crystallography, using a method that exploits commonly encountered imperfect crystals and enables model free phasing. PMID- 26863982 TI - Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche. AB - Haematopoietic stem cells (HSCs) are arguably the most extensively characterized tissue stem cells. Since the identification of HSCs by prospective isolation, complex multi-parameter flow cytometric isolation of phenotypic subsets has facilitated studies on many aspects of HSC biology, including self-renewal, differentiation, ageing, niche, and diversity. Here we demonstrate by unbiased multi-step screening, identification of a single gene, homeobox B5 (Hoxb5, also known as Hox-2.1), with expression in the bone marrow that is limited to long term (LT)-HSCs in mice. Using a mouse single-colour tri-mCherry reporter driven by endogenous Hoxb5 regulation, we show that only the Hoxb5(+) HSCs exhibit long term reconstitution capacity after transplantation in primary transplant recipients and, notably, in secondary recipients. Only 7-35% of various previously defined immunophenotypic HSCs are LT-HSCs. Finally, by in situ imaging of mouse bone marrow, we show that >94% of LT-HSCs (Hoxb5(+)) are directly attached to VE-cadherin(+) cells, implicating the perivascular space as a near homogenous location of LT-HSCs. PMID- 26863983 TI - Structure- and function-based design of Plasmodium-selective proteasome inhibitors. AB - The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome, resulting in toxicity that precludes their use as therapeutic agents. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, here we use a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We design inhibitors based on amino-acid preferences specific to the parasite proteasome, and find that they preferentially inhibit the beta2-subunit. We determine the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy and single-particle analysis, to a resolution of 3.6 A. These data reveal the unusually open P. falciparum beta2 active site and provide valuable information about active-site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin family anti-malarials, we observe growth inhibition synergism with low doses of this beta2-selective inhibitor in artemisinin-sensitive and resistant parasites. Finally, we demonstrate that a parasite-selective inhibitor could be used to attenuate parasite growth in vivo without appreciable toxicity to the host. Thus, the Plasmodium proteasome is a chemically tractable target that could be exploited by next-generation anti-malarial agents. PMID- 26863986 TI - Interrater Reliability of mHealth App Rating Measures: Analysis of Top Depression and Smoking Cessation Apps. AB - BACKGROUND: There are over 165,000 mHealth apps currently available to patients, but few have undergone an external quality review. Furthermore, no standardized review method exists, and little has been done to examine the consistency of the evaluation systems themselves. OBJECTIVE: We sought to determine which measures for evaluating the quality of mHealth apps have the greatest interrater reliability. METHODS: We identified 22 measures for evaluating the quality of apps from the literature. A panel of 6 reviewers reviewed the top 10 depression apps and 10 smoking cessation apps from the Apple iTunes App Store on these measures. Krippendorff's alpha was calculated for each of the measures and reported by app category and in aggregate. RESULTS: The measure for interactiveness and feedback was found to have the greatest overall interrater reliability (alpha=.69). Presence of password protection (alpha=.65), whether the app was uploaded by a health care agency (alpha=.63), the number of consumer ratings (alpha=.59), and several other measures had moderate interrater reliability (alphas>.5). There was the least agreement over whether apps had errors or performance issues (alpha=.15), stated advertising policies (alpha=.16), and were easy to use (alpha=.18). There were substantial differences in the interrater reliabilities of a number of measures when they were applied to depression versus smoking apps. CONCLUSIONS: We found wide variation in the interrater reliability of measures used to evaluate apps, and some measures are more robust across categories of apps than others. The measures with the highest degree of interrater reliability tended to be those that involved the least rater discretion. Clinical quality measures such as effectiveness, ease of use, and performance had relatively poor interrater reliability. Subsequent research is needed to determine consistent means for evaluating the performance of apps. Patients and clinicians should consider conducting their own assessments of apps, in conjunction with evaluating information from reviews. PMID- 26863985 TI - Microbial extracellular electron transfer and its relevance to iron corrosion. AB - Extracellular electron transfer (EET) is a microbial metabolism that enables efficient electron transfer between microbial cells and extracellular solid materials. Microorganisms harbouring EET abilities have received considerable attention for their various biotechnological applications, including bioleaching and bioelectrochemical systems. On the other hand, recent research revealed that microbial EET potentially induces corrosion of iron structures. It has been well known that corrosion of iron occurring under anoxic conditions is mostly caused by microbial activities, which is termed as microbiologically influenced corrosion (MIC). Among diverse MIC mechanisms, microbial EET activity that enhances corrosion via direct uptake of electrons from metallic iron, specifically termed as electrical MIC (EMIC), has been regarded as one of the major causative factors. The EMIC-inducing microorganisms initially identified were certain sulfate-reducing bacteria and methanogenic archaea isolated from marine environments. Subsequently, abilities to induce EMIC were also demonstrated in diverse anaerobic microorganisms in freshwater environments and oil fields, including acetogenic bacteria and nitrate-reducing bacteria. Abilities of EET and EMIC are now regarded as microbial traits more widespread among diverse microbial clades than was thought previously. In this review, basic understandings of microbial EET and recent progresses in the EMIC research are introduced. PMID- 26863987 TI - Urinary incontinence symptoms and impact on quality of life in patients seeking outpatient physical therapy services. AB - OBJECTIVE: The objective of this study was to examine the frequency and types of urinary incontinence (UI) in patients seeking outpatient physical therapy for neuro-musculoskeletal conditions. DESIGN: Retrospective cross-sectional analysis. PATIENTS: A convenience sample of patients that positively responded to a UI screening question was included in this study. METHODS: Data were collected for age, sex, and primary treatment condition classified into one of the following (i.e., urinary dysfunction, fecal dysfunction, pelvic pain, spine, neurological disorders, or extremity disorders); UI type (i.e., mixed, urge, stress, or insensible); UI symptom severity; and quality of life (QoL) impact. MAIN OUTCOME MEASURES: Frequency of UI type, symptom severity, health-related quality of life (HRQoL) impact, and pad use were compared between treatment groups. RESULTS: The mean age of the sample (n = 599) was 49.8 years (SD = 18.5) and 94.7% were female. The urinary dysfunction group comprised 44.2% of the total sample, followed by the spine group with 25.7% and pelvic pain with 17.2%. The urinary dysfunction group scored significantly higher on UI symptom severity and impact on QoL compared to the pelvic pain and spine groups, but not compared to the extremity disorders, fecal dysfunction, or neurological disorder group. CONCLUSION: These preliminary data indicate that UI is a condition afflicting many individuals who present to outpatient physical therapy beyond those seeking care for UI. We recommend using a simple screening measure for UI and its impact on HRQoL as part of a routine initial evaluation in outpatient physical therapy settings. PMID- 26863988 TI - Myosin di-phosphorylation and peripheral actin bundle formation as initial events during endothelial barrier disruption. AB - The phosphorylation of the 20-kD myosin light chain (MLC) and actin filament formation play a key role in endothelial barrier disruption. MLC is either mono- or di-phosphorylated (pMLC and ppMLC) at T18 or S19. The present study investigated whether there are any distinct roles of pMLC and ppMLC in barrier disruption induced by thrombin. Thrombin induced a modest bi-phasic increase in pMLC and a robust mono-phasic increase in ppMLC. pMLC localized in the perinuclear cytoplasm during the initial phase, while ppMLC localized in the cell periphery, where actin bundles were formed. Later, the actin bundles were rearranged into stress fibers, where pMLC co-localized. Rho-kinase inhibitors inhibited thrombin-induced barrier disruption and peripheral localization of ppMLC and actin bundles. The double, but not single, mutation of phosphorylation sites abolished the formation of peripheral actin bundles and the barrier disruption, indicating that mono-phosphorylation of MLC at either T18 or S19 is functionally sufficient for barrier disruption. Namely, the peripheral localization, but not the degree of phosphorylation, is suggested to be essential for the functional effect of ppMLC. These results suggest that MLC phosphorylation and actin bundle formation in cell periphery are initial events during barrier disruption. PMID- 26863992 TI - Temporary Charge Carrier Separation Dominates the Photoluminescence Decay Dynamics of Colloidal CdSe Nanoplatelets. AB - Luminescent colloidal CdSe nanoplatelets with atomically defined thicknesses have recently been developed, and their potential for various applications has been shown. To understand their special properties, experiments have until now focused on the relatively short time scales of at most a few nanoseconds. Here, we measure the photoluminescence decay dynamics of colloidal nanoplatelets on time scales up to tens of microseconds. The excited state dynamics are found to be dominated by the slow (~MUs) dynamics of temporary exciton storage in a charge separated state, previously overlooked. We study the processes of charge carrier separation and exciton recovery in pure CdSe nanoplatelets as well as in core crown and core-shell CdSe/CdS nanoplatelets with high ensemble quantum yields of 50%, and discuss the implications. Our work highlights the importance of reversible charge carrier trapping and experiments over a wide range of time scales for the understanding of colloidal nanoemitters in general and nanoplatelets in particular. PMID- 26863993 TI - Sponge cell reaggregation: Cellular structure and morphogenetic potencies of multicellular aggregates. AB - Sponges (phylum Porifera) are one of the most ancient extant multicellular animals and can provide valuable insights into origin and early evolution of Metazoa. High plasticity of cell differentiations and anatomical structure is characteristic feature of sponges. Present study deals with sponge cell reaggregation after dissociation as the most outstanding case of sponge plasticity. Dynamic of cell reaggregation and structure of multicellular aggregates of three demosponge species (Halichondria panicea (Pallas, 1766), Haliclona aquaeductus (Sshmidt, 1862), and Halisarca dujardinii Johnston, 1842) were studied. Sponge tissue dissociation was performed mechanically. Resulting cell suspensions were cultured at 8-10 degrees C for at least 5 days. Structure of multicellular aggregates was studied by light, transmission and scanning electron microscopy. Studied species share common stages of cell reaggregation primary multicellular aggregates, early-stage primmorphs and primmorphs, but the rate of reaggregation varies considerably among species. Only cells of H. dujardinii are able to reconstruct functional and viable sponge after primmorphs formation. Sponge reconstruction in this species occurs due to active cell locomotion. Development of H. aquaeductus and H. panicea cells ceases at the stages of early primmorphs and primmorphs, respectively. Development of aggregates of these species is most likely arrested due to immobility of the majority of cells inside them. However, the inability of certain sponge species to reconstruct functional and viable individuals during cell reaggregation may be not a permanent species-specific characteristic, but depends on various factors, including the stage of the life cycle and experimental conditions. PMID- 26863994 TI - C15039. Activation Methods of Carbonaceous Materials Obtained from Agricultural Waste. A Review. AB - Activated carbons belong to the most widely used adsorbent materials. The utility of these materials mainly depends on their chemical surface and porous structure. The method of activation and the nature of the used precursor greatly influence the pore structure and surface functional groups of the activated carbon. Therefore, the main objective of current investigations is to develop or modify the activation method in an optimal manner using appropriate precursors. This review compiles the results of various studies on the synthesis of activated carbons from agricultural waste. Various activation methods, such as physical, chemical, physicochemical, and microwave activation, are discussed. The effects of carbonization and activation parameters, such as temperature, activating agent, and residence time, towards the properties of the activated carbon are reviewed. This article is protected by copyright. All rights reserved. PMID- 26863991 TI - L-arginine promotes gut hormone release and reduces food intake in rodents. AB - AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity. PMID- 26863995 TI - Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs. AB - Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 ug/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS. PMID- 26863996 TI - Prevalence and associated factors of sarcopenia in elderly subjects with amnestic mild cognitive impairment or Alzheimer disease. AB - BACKGROUND: To date, very little is known about the nature of sarcopenia in subjects with cognitive impairment. The aims of this study were firstly to clarify the prevalence of sarcopenia at various stages of cognitive impairment, and secondly to examine factors related to sarcopenia in men and women with cognitive impairment. METHOD: The subjects were 418 outpatients (normal cognition; NC: 35, amnestic mild cognitive impairment; aMCI: 40, Alzheimer disease; AD: 343) who attended the Memory Clinic at the National Center for Geriatrics and Gerontology of Japan during the period from October 2010 to July 2014. Cognitive status, vitality, depressive mood, body mass index, hand grip strength, timed up and go test, skeletal muscle mass and serum levels of 25 hydroxyvitamin D, albumin and creatinine were assessed. Sarcopenia was defined as the presence of both poor muscle function (low physical performance or low muscle strength) and low muscle mass. We performed the univariate and multivariate logistic regression analyses to explore factors associated with sarcopenia. RESULTS: The overall prevalence of sarcopenia was 21.1% (NC = 8.6%, aMCI = 12.5%, AD = 23.3%). In both sexes, factors associated with sarcopenia were age (P < .01), body mass index (P < .001) and vitality (P < .05). In women, serum level of 25-hydroxyvitamin D was associated with sarcopenia (P < .05). CONCLUSION: Low vitality could be a dementia-specific risk factor for sarcopenia. Prevention of sarcopenia in patients with cognitive impairment should be approached from physical and psychologic points of view. PMID- 26863997 TI - Factors Associated With Health-Related Quality of Life in Children With Duchenne Muscular Dystrophy. AB - This study investigated clinical and family characteristics associated with health-related quality of life in children with Duchenne muscular dystrophy. Families of 176 boys with Duchenne muscular dystrophy were identified and mailed questionnaires via the Canadian Neuromuscular Disease Registry. Multiple linear regressions analyses were used to examine the relationship between clinical and family characteristics and child-self and parent-proxy reported health-related quality of life. Greater fatigue and use of wheelchairs were consistently associated with worse health-related quality of life independent of other factors. Higher household income and parent having a postsecondary degree were associated with better health-related quality of life in some of the measures. A greater clinical focus on and efforts to reduce fatigue could lead to improvement of health-related quality of life in the Duchenne muscular dystrophy population. This study also sets the ground for longitudinal studies where changes in health related quality of life can be monitored over time. PMID- 26863998 TI - A Pilot Study of Obesogenic Eating Behaviors in Children With Migraine. AB - We studied associations between migraine severity and obesogenic eating behaviors in children with a prospective cross-sectional, clinic-based study. Migraine severity was quantified using the PedMIDAS tool and attack frequency. Eating behaviors were assessed using the Dutch Eating Behaviour Questionnaire and the Child Eating Behaviour Questionnaire. Food intake was assessed using a Food Intake Questionnaire. Statistical tests of association between eating behavior, food intake, and adiposity with migraine severity were performed. Sixty children (mean age = 10.9 years, standard deviation = 3.1; 26 males) were recruited. There was a positive correlation between the Child Eating Behaviour Questionnaire desire to drink subscale and PedMIDAS scores (r = 0.41, P = .01). Attack frequency was associated with higher intake of high fat or sugar content food and drink (r = 0.27, P = .04). No association between migraine severity and adiposity was found. Suggestion that migraine severity in children is associated with certain obesogenic eating behaviors requires further large study investigation. PMID- 26863999 TI - Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis. AB - Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. PMID- 26864000 TI - Alp7/TACC-Alp14/TOG generates long-lived, fast-growing MTs by an unconventional mechanism. AB - Alp14 is a TOG-family microtubule polymerase from S. pombe that tracks plus ends and accelerates their growth. To interrogate its mechanism, we reconstituted dynamically unstable single isoform S. pombe microtubules with full length Alp14/TOG and Alp7, the TACC-family binding partner of Alp14. We find that Alp14 can drive microtubule plus end growth at GTP-tubulin concentrations at least 10 fold below the usual critical concentration, at the expense of increased catastrophe. This reveals Alp14 to be a highly unusual enzyme that biases the equilibrium for the reaction that it catalyses. Alp7/TACC enhances the effectiveness of Alp14, by increasing its occupancy. Consistent with this, we show in live cells that Alp7 deletion produces very similar MT dynamics defects to Alp14 deletion. The ability of Alp7/14 to accelerate and bias GTP-tubulin exchange at microtubule plus ends allows it to generate long-lived, fast-growing microtubules at very low cellular free tubulin concentrations. PMID- 26864001 TI - Changes in ectocervical surface area in women throughout pregnancy compared to non-pregnant and postpartum states. AB - OBJECTIVE: The objective of this study is to estimate changes in the surface area of the ectocervix (CA) in women during pregnancy and compare this to postpartum and non-pregnant states. METHODS: CA was evaluated in 210 normal nulliparous women divided into groups from early to late gestation, 40 postpartum women, and 25 non-pregnant women. CA in cm(2) was estimated from analysis of images taken with an endoscope of the cervical face and an mm scale. An mm scale was also used to determine fornix length and fornix area computed. RESULTS: The face, fornix, and total areas of the CA of non-pregnant and postpartum groups are significantly smaller (p < 0.001) than these areas in groups during pregnancy. Generally, the CA of the face, fornix, and total area are also less in early pregnancy compared with late gestation (p < 0.01 to <0.001). Total CA correlates with gestational age (r = 0.196, p < 0.004). CONCLUSIONS: (1) During pregnancy, CA slowly and progressively increases to >75% area compared with CA of non-pregnant patients and then reverts back to low CA postpartum. (2) Increases in CA during pregnancy occur in both the face and fornix areas. (3) Increases in CA reflect enlargement in cervical volume and remodeling during pregnancy. PMID- 26864002 TI - A randomised controlled trial of intrathecal blockade versus peripheral nerve blockade for day-case knee arthroscopy. AB - We allocated 100 patients scheduled for day-case knee arthroscopy to unilateral spinal anaesthesia with 40 mg intrathecal hyperbaric prilocaine or to ultrasound guided femoral-sciatic nerve blockade with 25 ml mepivacaine 2%, 50 participants each. The median (IQR [range]) time to walk was 285 (240-330 [160-515]) min after intrathecal anaesthesia vs 328 (280-362 [150-435]) min after peripheral nerve blockade, p = 0.007. The median (IQR [range]) time to home discharge was 310 (260 350 [160-520]) min after intrathecal anaesthesia vs 335 (290-395 [190-440]) min after peripheral nerve blockade, p = 0.016. There was no difference in time from anaesthetic preparation to readiness for surgery. PMID- 26864003 TI - Deferred cord clamping at caesarean section--yet another use for videolaryngoscopy. PMID- 26864004 TI - The isolated forearm technique in non-paralysed patients. PMID- 26864005 TI - The isolated forearm technique in non-paralysed patients - a reply. PMID- 26864006 TI - Obstetric tracheal intubation guidelines and cricoid pressure. PMID- 26864007 TI - Obstetric tracheal intubation guidelines and cricoid pressure--a reply. PMID- 26864008 TI - Anaesthetic rooms and patient anxiety. PMID- 26864009 TI - More on the risks of inconsistent drug packaging and ampoule labelling. PMID- 26864010 TI - Prefilled insulin syringes. PMID- 26864011 TI - The effect of blowing a whistle on the cross-sectional area of the internal jugular vein. PMID- 26864013 TI - Correction. PMID- 26864012 TI - SORT maneuver for nasogastric tube insertion. PMID- 26864014 TI - Correction. PMID- 26864015 TI - Nonphotochemical Chlorophyll Fluorescence Quenching: Mechanism and Effectiveness in Protecting Plants from Photodamage. AB - We review the mechanism underlying nonphotochemical chlorophyll fluorescence quenching (NPQ) and its role in protecting plants against photoinhibition. This review includes an introduction to this phenomenon, a brief history of major milestones in our understanding of NPQ, definitions, and a discussion of quantitative measurements of NPQ We discuss the current knowledge and unknown aspects in the NPQ scenario, including the following: DeltapH, the proton gradient (trigger); light-harvesting complex II (LHCII), PSII light harvesting antenna (site); and changes in the antenna induced by DeltapH (change), which lead to the creation of the quencher We conclude that the minimum requirements for NPQ in vivo are DeltapH, LHCII complexes, and the PsbS protein. We highlight the most important unknown in the NPQ scenario, the mechanism by which PsbS acts upon the LHCII antenna. Finally, we describe a novel, emerging technology for assessing the photoprotective "power" of NPQ and the important findings obtained through this technology. PMID- 26864016 TI - Homodimerization of Ehd1 Is Required to Induce Flowering in Rice. AB - In plants, flowering time is elaborately controlled by various environment factors. Ultimately, florigens such as FLOWERING LOCUS T (FT) or FT-like molecules induce flowering. In rice (Oryza sativa), Early heading date 1 (Ehd1) is a major inducer of florigen gene expression. Although Ehd1 is highly homologous to the type-B response regulator (RR) family in the cytokinin signaling pathway, its precise molecular mechanism is not well understood. In this study, we showed that the C-terminal portion of the protein containing the GARP DNA-binding (G) domain can promote flowering when overexpressed. We also observed that the N-terminal portion of Ehd1, carrying the receiver (R) domain, delays flowering by inhibiting endogenous Ehd1 activity. Ehd1 protein forms a homomer via a 16-amino acid region in the inter domain between R and G. From the site-directed mutagenesis analyses, we demonstrated that phosphorylation of the Asp-63 residue within the R domain induces the homomerization of Ehd1, which is crucial for Ehd1 activity. A type-A RR, OsRR1, physically interacts with Ehd1 to form a heterodimer. In addition, OsRR1-overexpressing plants show a late flowering phenotype. Based on these observations, we conclude that OsRR1 inhibits Ehd1 activity by binding to form an inactive complex. PMID- 26864018 TI - Designing disordered materials using DNA-coated colloids of bacteriophage fd and gold. AB - DNA has emerged as an exciting binding agent for programmable colloidal self assembly. Its popularity derives from its unique properties: it provides highly specific short-ranged interactions and at the same time it acts as a steric stabilizer against non-specific van der Waals and Coulomb interactions. Because complementary DNA strands are linked only via hydrogen bonds, DNA-mediated binding is thermally reversible: it provides an effective attraction that can be switched off by raising the temperature only by a few degrees. In this article we introduce a new binary system made of DNA-functionalized filamentous fd viruses of ~880 nm length with an aspect ratio of ~100, and 50 nm gold nanoparticles (gold NPs) coated with the complementary DNA strands. When quenching mixtures below the melt temperature Tm, at which the attraction is switched on, we observe aggregation. Conversely, above Tm the system melts into a homogenous particulate 'gas'. We present the aggregation behavior of three different gold NP to virus ratios and compare them to a gel made solely of gold NPs. In particular, we have investigated the aggregate structures as a function of cooling rate and determine how they evolve as function of time for given quench depths, employing fluorescence microscopy. Structural information was extracted in the form of an effective structure factor and chord length distributions. Rapid cooling rates lead to open aggregates, while slower controlled cooling rates closer to equilibrium DNA hybridization lead to more fine-stranded gels. Despite the different structures we find that for both cooling rates the quench into the two phase region leads to initial spinodal decomposition, which becomes arrested. Surprisingly, although the fine-stranded gel is disordered, the overall structure and the corresponding length scale distributions in the system are remarkably reproducible. Such highly porous systems can be developed into new functional materials. PMID- 26864017 TI - Oligonucleotide-Mediated Genome Editing Provides Precision and Function to Engineered Nucleases and Antibiotics in Plants. AB - Here, we report a form of oligonucleotide-directed mutagenesis for precision genome editing in plants that uses single-stranded oligonucleotides (ssODNs) to precisely and efficiently generate genome edits at DNA strand lesions made by DNA double strand break reagents. Employing a transgene model in Arabidopsis (Arabidopsis thaliana), we obtained a high frequency of precise targeted genome edits when ssODNs were introduced into protoplasts that were pretreated with the glycopeptide antibiotic phleomycin, a nonspecific DNA double strand breaker. Simultaneous delivery of ssODN and a site-specific DNA double strand breaker, either transcription activator-like effector nucleases (TALENs) or clustered, regularly interspaced, short palindromic repeats (CRISPR/Cas9), resulted in a much greater targeted genome-editing frequency compared with treatment with DNA double strand-breaking reagents alone. Using this site-specific approach, we applied the combination of ssODN and CRISPR/Cas9 to develop an herbicide tolerance trait in flax (Linum usitatissimum) by precisely editing the 5' ENOLPYRUVYLSHIKIMATE-3-PHOSPHATE SYNTHASE (EPSPS) genes. EPSPS edits occurred at sufficient frequency that we could regenerate whole plants from edited protoplasts without employing selection. These plants were subsequently determined to be tolerant to the herbicide glyphosate in greenhouse spray tests. Progeny (C1) of these plants showed the expected Mendelian segregation of EPSPS edits. Our findings show the enormous potential of using a genome-editing platform for precise, reliable trait development in crop plants. PMID- 26864019 TI - Variations in schools' commitment to health and implementation of health improvement activities: a cross-sectional study of secondary schools in Wales. AB - BACKGROUND: Interventions to improve young people's health are most commonly delivered via schools. While young people attending the lowest socioeconomic status (SES) schools report poorer health profiles, no previous studies have examined whether there is an 'inverse care law' in school health improvement activity (i.e., whether schools in more affluent areas deliver more health improvement). Nor have other factors that may explain variations, such as leadership of health improvement activities, been examined at a population level. This paper examines variability in delivery of health improvement actions among secondary schools in Wales, and whether variability is linked to organisational commitment to health, socioeconomic status and school size. METHODS: Of the 82 schools participating in the 2013/14 Health Behaviour in School-aged Children (HBSC) survey in Wales, 67 completed a questionnaire on school health improvement delivery structures and health improvement actions within their school. Correlational analyses explore associations of delivery of health improvement activity among schools in Wales with organisational commitment to health, socioeconomic context and school size. RESULTS: There is substantial variability among schools in organisational commitment to health, with pupil emotional health identified as a priority by 52 % of schools, and physical health by 43 %. Approximately half (49 %) report written action plans for pupil health. Based on composite measures, the quantity of school health improvement activity was greater in less affluent schools and schools reporting greater commitment to health. There was a consistent though non-significant trend toward more health improvement activity in larger schools. In multivariate analysis deprivation (OR = 1.06; 95 % CI = 1.01 to 1.12) and organisational commitment to health were significant independent predictors of the quantity of health improvement (OR = 1.60; 95 % CI = 1.15 to 2.22). CONCLUSIONS: There is no evidence of an 'inverse care law' in school health, with some evidence of more comprehensive, multi-level health improvement activity in more deprived schools. This large-scale, quantitative analysis supports previous smaller scale, qualitative studies/process evaluations that suggest that senior management team commitment to delivering health improvement, and formulating and reviewing progress against written action plans, are important for facilitating the delivery of comprehensive interventions. PMID- 26864020 TI - Revisiting chromatin binding of the Arabidopsis UV-B photoreceptor UVR8. AB - BACKGROUND: Plants perceive UV-B through the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor and UVR8 activation leads to changes in gene expression such as those associated with UV-B acclimation and stress tolerance. Albeit functionally unrelated, UVR8 shows some homology with RCC1 (Regulator of Chromatin Condensation 1) proteins from non-plant organisms at the sequence level. These proteins act as guanine nucleotide exchange factors for Ran GTPases and bind chromatin via histones. Subsequent to the revelation of this sequence homology, evidence was presented showing that UVR8 activity involves interaction with chromatin at the loci of some target genes through histone binding. This suggested a UVR8 mode-of-action intimately and directly linked with gene transcription. However, several aspects of UVR8 chromatin association remained undefined, namely the impact of UV-B on the process and how UVR8 chromatin association related to the transcription factor ELONGATED HYPOCOTYL 5 (HY5), which is important for UV-B signalling and has overlapping chromatin targets. Therefore, we have investigated UVR8 chromatin association in further detail. RESULTS: Unlike the claims of previous studies, our chromatin immunoprecipitation (ChIP) experiments do not confirm UVR8 chromatin association. In contrast to human RCC1, recombinant UVR8 also does not bind nucleosomes in vitro. Moreover, fusion of a VP16 activation domain to UVR8 did not alter expression of proposed UVR8 target genes in transient gene expression assays. Finally, comparison of the Drosophila DmRCC1 and the Arabidopsis UVR8 crystal structures revealed that critical histone- and DNA-interaction residues apparent in DmRCC1 are not conserved in UVR8. CONCLUSION: This has led us to conclude that the cellular activity of UVR8 likely does not involve its specific binding to chromatin at target genes. PMID- 26864021 TI - The influence of inhaled multi-walled carbon nanotubes on the autonomic nervous system. AB - BACKGROUND: Heart rate and cardiovascular function are regulated by the autonomic nervous system. Heart rate variability (HRV) as a marker reflects the activity of autonomic nervous system. The prognostic significance of HRV in cardiovascular disease has been reported in clinical and epidemiological studies. The present study focused on the influence of inhaled multi-walled carbon nanotubes (MWCNTs) on autonomic nervous system by HRV analysis. METHODS: Male Sprague-Dawley rats were pre-implanted with a telemetry device and kept in the individual cages for recovery. At week four after device implantation, rats were exposed to MWCNTs for 5 h at a concentration of 5 mg/m(3). The real-time EKGs were recorded by a telemetry system at pre-exposure, during exposure, 1 day and 7 days post exposure. HRV was measured by root mean square of successive differences (RMSSD); the standard deviation of inter-beat (RR) interval (SDNN); the percentage of successive RR interval differences greater than 5 ms (pNN5) and 10 ms (pNN10); low frequency (LF) and high frequency (HF). RESULTS: Exposure to MWCNTs increased the percentage of differences between adjacent R-R intervals over 10 ms (pNN10) (p < 0.01), RMSSD (p < 0.01), LF (p < 0.05) and HF (p < 0.01). CONCLUSIONS: Inhalation of MWCNTs significantly alters the balance between sympathetic and parasympathetic nervous system. Whether such transient alterations in autonomic nervous performance would alter cardiovascular function and raise the risk of cardiovascular events in people with pre-existing cardiovascular conditions warrants further study. PMID- 26864022 TI - Reduction in resource use with the misoprostol vaginal insert vs the dinoprostone vaginal insert for labour induction: a model-based analysis from a United Kingdom healthcare perspective. AB - BACKGROUND: In view of the increasing pressure on the UK's maternity units, new methods of labour induction are required to alleviate the burden on the National Health Service, while maintaining the quality of care for women during delivery. A model was developed to evaluate the resource use associated with misoprostol vaginal inserts (MVIs) and dinoprostone vaginal inserts (DVIs) for the induction of labour at term. METHODS: The one-year Markov model estimated clinical outcomes in a hypothetical cohort of 1397 pregnant women (parous and nulliparous) induced with either MVI or DVI at Southmead Hospital, Bristol, UK. Efficacy and safety data were based on published and unpublished results from a phase III, double blind, multicentre, randomised controlled trial. Resource use was modelled using data from labour induction during antenatal admission to patient discharge from Southmead Hospital. The model's sensitivity to key parameters was explored in deterministic multi-way and scenario-based analyses. RESULTS: Over one year, the model results indicated MVI use could lead to a reduction of 10,201 h (28.9%) in the time to vaginal delivery, and an increase of 121% and 52% in the proportion of women achieving vaginal delivery at 12 and 24 h, respectively, compared with DVI use. Inducing women with the MVI could lead to a 25.2% reduction in the number of midwife shifts spent managing labour induction and 451 fewer hospital bed days. These resource utilisation reductions may equate to a potential 27.4% increase in birthing capacity at Southmead Hospital, when using the MVI instead of the DVI. CONCLUSIONS: Resource use, in addition to clinical considerations, should be considered when making decisions about labour induction methods. Our model analysis suggests the MVI is an effective method for labour induction, and could lead to a considerable reduction in resource use compared with the DVI, thereby alleviating the increasing burden of labour induction in UK hospitals. PMID- 26864024 TI - Intestinal spirochaetes (Brachyspira species) in pheasants in Great Britain. PMID- 26864023 TI - Sand flies (Diptera, Psychodidae, Phlebotominae), vectors of Leishmania protozoa, at an Atlantic Forest Conservation Unit in the municipality of Nisia Floresta, Rio Grande do Norte state, Brazil. AB - BACKGROUND: Sand flies are insect vectors of protozoa from the genus Leishmania, causative parasites of visceral and American tegumentary leishmaniases. The present study discusses the bioecological aspects of sand fly species, transmitters of Leishmania protozoa, in different ecotopes of an Atlantic Forest Conservation Unit located in the metropolitan region of Natal, Rio Grande do Norte state, Brazil. METHODS: Two monthly captures were made in 1 year, using CDC light traps, in two anthropized and two preserved environments. RESULTS: A total of 2936 sand flies belonging to the following ten species were captured: Evandromyia walkeri, Evandromyia evandroi, Psychodopygus wellcomei, Sciopemyia sordellii, Psathyromyia brasiliensis, Lutzomyia longipalpis, Evandromyia lenti, Psathyromyia shannoni, Nyssomyia whitmani and Nyssomyia intermedia. The most common species was E. walkeri (77.6%), followed by E. evandroi (17.5%). Forest was the site with the greatest abundance (32.4%), followed by bamboo grove (26.3%). CONCLUSIONS: Sand flies were generally more abundant in the rainy season and L. longipalpis, a vector species of Leishmania infantum, was adapted to anthropized environments. It was confirmed that P. wellcomei, a vector of Leishmania braziliensis in Amazonia, is a species associated with more preserved environments, and occurs only in the rainy season. PMID- 26864025 TI - Veterinary treatment strategies for clinical mastitis in dairy cows in Sweden. AB - To evaluate if Swedish veterinary guidelines on use of antimicrobials in cases of clinical mastitis in dairy cows have been adopted by veterinary practitioners, their treatment strategies were evaluated in a cross-sectional study using a web based questionnaire. Another aim was to study if the strategies differed among veterinarians due to year and country of exam, sex, region, numbers of mastitis cases per month, and postgraduate training in herd health using multivariable logistic regression models. In total, 267 of 741 (36 per cent) veterinarians contacted answered the questionnaire satisfactorily. Most considered bacteriological diagnostics important, but many veterinarians made treatment decisions without collecting information on antimicrobial susceptibility. Moreover, few veterinarians used measuring tape to assess bodyweight before dosing parenteral antimicrobials. Year of exam and postgraduate training were the veterinary demographic factors associated with most treatment routines. The questions associated with most demographic factors were if antimicrobial treatment is affected by knowledge on earlier udder pathogens in the herd, and how often NSAID and follow-up of treatment using milk somatic cell count are used. Overall, the veterinarians followed the Swedish guidelines rather well, but discrepancies in need for improvement were found. PMID- 26864027 TI - Comparison of commercial type 1 and type 2 PRRSV vaccines against heterologous dual challenge. AB - This study was to compare the effect of vaccination of pigs with either type 1 or type 2 porcine reproductive and respiratory syndrome virus (PRRSV) against heterologous dual challenge of both genotypes. Pigs were administered type 1 (UNISTRAIN PRRS) or type 2 (Fostera PRRS) PRRSV vaccine at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Vaccination of pigs with type 1 PRRSV was able to reduce the levels of type 1 but not type 2 PRRSV viraemia, whereas vaccination of pigs with type 2 PRRSV was able to reduce the levels of type 1 and type 2 PRRSV viraemia against a dual challenge. Vaccination of pigs with type 2 PRRSV significantly reduced lung lesions after dual challenge compared with vaccination of pigs with type 1 PRRSV. Vaccination of pigs with type 2 PRRSV induced higher numbers of type 1 and type 2 PRRSV specific interferon-gamma secreting cells compared with vaccination of pigs with type 1 PRRSV after dual challenge. The results of this study demonstrated that vaccination of pigs with type 2 PRRSV is efficacious in protecting growing pigs from respiratory disease after heterologous dual type 1 and type 2 PRRSV challenge compared with vaccination of pigs with type 1 PRRSV. PMID- 26864026 TI - Absence of circulation of Pestivirus between wild and domestic ruminants in southern Spain. AB - Ruminant pestiviruses (family Flaviviridae) affect both wild and domestic ruminants worldwide, causing reproductive disorders and severe economic losses. Wild (n=1442) and domestic (n=373) ruminants from southern Spain were tested for the presence of antibodies to pestiviruses. Seropositivity was detected by both ELISA and virus neutralisation test in 1/892 (0.1 per cent) red deer, 29/125 (23.2 per cent) cattle and 17/157 (10.8 per cent) sheep. Pestivirus-specific antibodies to bovine viral diarrhoea virus (BVDV) and border disease virus (BDV) genotypes 1, 4 and 5 were detected. Significantly higher antibody titres to BDV-4 compared with BVDV-NADL were found in one cattle farm. Results indicate that wild ruminants may act as spillover hosts from domestic ruminants, and therefore they do not represent a risk for domestic ruminants in southern Spain. The wide distribution of pestiviruses among sheep and cattle suggests that transmission between these species may occur. PMID- 26864028 TI - Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus. AB - Synergistic effects between the same class of antibiotics are rarely reported. In the current study, two amphenicols, namely florfenicol and thiamphenicol, exhibited both in vitro and in vivo synergism against clinical isolates ofStaphylococcus aureusfrom chickens, cattle and pigs. Checkerboard assays on 21S. aureusisolates showed that in 80 per cent of methicillin-susceptibleS. aureus(MSSA) and 82 per cent of methicillin-resistantS. aureus(MRSA) isolates tested, the minimal inhibitory concentration (MIC) of florfenicol could be reduced by 75 per cent (1/4 MIC) or more (up to 1/16 MIC) when combined with 1/2 MIC of thiamphenicol to exhibit antimicrobial activity comparable to the respective drugs at original strength (1*MIC). A synergistic effect (fractional inhibitory concentration index <=0.5 or >=2-log10decrease in colony-forming unit/ml in time-kill study) was evident against 30 per cent of MSSA and 45 per cent of MRSA strains tested. A study in mice revealed that the florfenicol/thiamphenicol combination at reduced dosages provided sufficient protection againstS. aureuschallenge. The possible mechanism warrants further study but likely includes the facilitated uptake of thiamphenicol via florfenicol action, and this facilitation was not limited to amphenicol class. The present study may offer new strategy for combination therapy and provide potential alternatives for effective treatment againstS. aureusinfections. PMID- 26864029 TI - Oral Immunization of Mice with Live Pneumocystis murina Protects against Pneumocystis Pneumonia. AB - Pneumocystis pneumonia is a major cause of morbidity and mortality in immunocompromised patients, particularly those infected with HIV. In this study, we evaluated the potential of oral immunization with live Pneumocystis to elicit protection against respiratory infection with Pneumocystis murina. C57BL/6 mice vaccinated with live P. murina using a prime-boost vaccination strategy were protected from a subsequent lung challenge with P. murina at 2, 7, 14, and 28 d postinfection even after CD4(+) T cell depletion. Specifically, vaccinated immunocompetent mice had significantly faster clearance than unvaccinated immunocompetent mice and unvaccinated CD4-depleted mice remained persistently infected with P. murina. Vaccination also increased numbers of CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD11b(+) macrophages in the lungs following respiratory infection. In addition, levels of lung, serum, and fecal P. murina specific IgG and IgA were increased in vaccinated animals. Furthermore, administration of serum from vaccinated mice significantly reduced Pneumocystis lung burden in infected animals compared with control serum. We also found that the diversity of the intestinal microbial community was altered by oral immunization with P. murina. To our knowledge, our data demonstrate for the first time that an oral vaccination strategy prevents Pneumocystis infection. PMID- 26864030 TI - Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations. AB - CD4(+) T cells that express the transcription factor FOXP3 (FOXP3(+) T cells) are commonly regarded as immunosuppressive regulatory T cells (Tregs). FOXP3(+) T cells are reported to be increased in tumor-bearing patients or animals and are considered to suppress antitumor immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation and that some non-Treg FOXP3(+) T cells, especially memory-phenotype FOXP3(low) cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3(+) T cells is fundamental for revealing the significance of FOXP3(+) T cells in tumor immunity, but the arbitrariness and complexity of manual gating have complicated the issue. In this article, we report a computational method to automatically identify and classify FOXP3(+) T cells into subsets using clustering algorithms. By analyzing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3(+) subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3(+) subpopulations. Interestingly, the computationally identified FOXP3(+) subpopulation included not only classical FOXP3(high) Tregs, but also memory-phenotype FOXP3(low) cells by manual gating. Furthermore, the proposed method successfully analyzed an independent data set, showing that the same FOXP3(+) subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3(+) T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3(+) T cells and Tregs. PMID- 26864031 TI - Mucosal Humoral Immune Response to SIVmac239?nef Vaccination and Vaginal Challenge. AB - Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV 1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium. We now examine the mucosal production of the Ab component of this system after vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized similar to follicles in secondary lymphoid organs, and we provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating Ab production, affinity maturation, and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine. PMID- 26864032 TI - Annexin A2 Limits Neutrophil Transendothelial Migration by Organizing the Spatial Distribution of ICAM-1. AB - ICAM-1 is required for firm adhesion of leukocytes to the endothelium. However, how the spatial organization of endothelial ICAM-1 regulates leukocyte adhesion is not well understood. In this study, we identified the calcium-effector protein annexin A2 as a novel binding partner for ICAM-1. ICAM-1 clustering promotes the ICAM-1-annexin A2 interaction and induces translocation of ICAM-1 into caveolin-1 rich membrane domains. Depletion of endothelial annexin A2 using RNA interference enhances ICAM-1 membrane mobility and prevents the translocation of ICAM-1 into caveolin-1-rich membrane domains. Surprisingly, this results in increased neutrophil adhesion and transendothelial migration under flow conditions and reduced crawling time, velocity, and lateral migration distance of neutrophils on the endothelium. In conclusion, our data show that annexin A2 limits neutrophil transendothelial migration by organizing the spatial distribution of ICAM-1. PMID- 26864033 TI - A Novel Vaccination Strategy Mediating the Induction of Lung-Resident Memory CD8 T Cells Confers Heterosubtypic Immunity against Future Pandemic Influenza Virus. AB - The currently used vaccine strategy to combat influenza A virus (IAV) aims to provide highly specific immunity to circulating seasonal IAV strains. However, the outbreak of 2009 influenza pandemic highlights the danger in this strategy. In this study, we tested the hypothesis that universal vaccination that offers broader but weaker protection would result in cross protective T cell responses after primary IAV infection, which would subsequently provide protective immunity against future pandemic strains. Specifically, we used tandem repeat extracellular domain of M2 (M2e) epitopes on virus-like particles (M2e5x VLP) that induced heterosubtypic immunity by eliciting Abs to a conserved M2e epitope. M2e5x VLP was found to be superior to strain-specific current split vaccine in conferring heterosubtypic cross protection and in equipping the host with cross protective lung-resident nucleoprotein-specific memory CD8(+) T cell responses to a subsequent secondary infection with a new pandemic potential strain. Immune correlates for subsequent heterosubtypic immunity by M2e5x VLP vaccination were found to be virus-specific CD8(+) T cells secreting IFN-gamma and expressing lung resident memory phenotypic markers CD69(+) and CD103(+) as well as M2e Abs. Hence, vaccination with M2e5x VLP may be developable as a new strategy to combat future pandemic outbreaks. PMID- 26864035 TI - Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor. AB - The generation of Abs that recognize the native conformation of G protein-coupled receptors can be a challenging task because, like most multimembrane-spanning proteins, they are extremely difficult to purify as native protein. By combining genetic immunization, phage display, and biopanning, we identified two functional monovalent Abs (nanobodies) targeting ChemR23. The two nanobodies (CA4910 and CA5183) were highly specific for the human receptor and bind ChemR23 with moderate affinity. Binding studies also showed that they share a common binding site that overlaps with that of chemerin, the natural ligand of ChemR23. Consistent with these results, we found that the nanobodies were able to antagonize chemerin-induced intracellular calcium increase. The inhibition was partial when chemerin was used as agonist and complete when the chemerin(149-157) nonapeptide was used as agonist. Engineering of a bivalent CA4910 nanobody resulted in a relatively modest increase in affinity but a marked enhancement of efficacy as an antagonist of chemerin induced intracellular calcium mobilization and a much higher potency against the chemerin(149-157) nonapeptide-induced response. We also demonstrated that the fluorescently labeled nanobodies detect ChemR23 on the surface of human primary cell populations as efficiently as a reference mouse mAb and that the bivalent CA4910 nanobody behaves as an efficient antagonist of chemerin-induced chemotaxis of human primary cells. Thus, these nanobodies constitute new tools to study the role of the chemerin/ChemR23 system in physiological and pathological conditions. PMID- 26864036 TI - Effect of Overproduction of Mitochondrial Uncoupling Protein 2 on Cos7 Cells: Induction of Senescent-like Morphology and Oncotic Cell Death. AB - BACKGROUND: The maintenance of mitochondrial membrane potential is essential for cell growth and survival. Mitochondrial uncoupling protein 2 plays the most important roles in uncoupling oxidative phosphorylation and decreasing mitochondrial O2- production by regulating the mitochondrial membrane potential. We propose that mouse UCP2 has two glycine-rich motifs, motif 1: EGIRGLWKG (170 178) and a known Walker A-like motif 2: EGPRAFYKG (264-272). These motifs seem to be important for the function of UCP2. OBJECTIVE: We investigated the biological effects of overproduced-UCP2 and its physiological consequence in Cos7 cells. METHOD: We introduced several amino acid changes in the motif 1. The expression vectors of the green fluorescent protein (GFP)-fused UCP2 and mutant UCP2 were constructed and expressed in Cos7 cells. RESULT: The UCP2-GFP-expressed cells significantly down-regulated the mitochondrial membrane potentials and induced the enlarged cell shapes. Next we generated the stably UCP2-GFP-expressed Cos7 cells by selection with the antibiotic Genecitin (G418). Within the first few weeks following G418-selection, the stably UCP2-GFP-expressed cells could not divide well and gradually manifested the irregular and enlarged senescent-like cell morphology. The UCP2/K177E- or UCP2/G174L-expressed cells did not induce the enlarged cell shapes. Hence, UCP2/K177E and UCP2/G174L produced the functional incompetence of the glycine-rich motif 1. The senescent-like cells significantly decreased the mitochondrial membrane potentials and finally died nearly one month. CONCLUSION: Overproduction of UCP2 irreversibly reduces the mitochondrial membrane potentials and induces the senescent-like morphology and finally oncotic cell death in Cos7 cells. These changes seem to occur from the irreversible metabolic changes following total loss of cellular ATP. PMID- 26864034 TI - Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity. AB - Heterologous immunity is recognized as a significant barrier to transplant tolerance. Whereas it has been established that pathogen-elicited memory T cells can have high or low affinity for cross-reactive allogeneic peptide-MHC, the role of TCR affinity during heterologous immunity has not been explored. We established a model with which to investigate the impact of TCR-priming affinity on memory T cell populations following a graft rechallenge. In contrast to high affinity priming, low-affinity priming elicited fully differentiated memory T cells with a CD45RB(hi) status. High CD45RB status enabled robust secondary responses in vivo, as demonstrated by faster graft rejection kinetics and greater proliferative responses. CD45RB blockade prolonged graft survival in low affinity primed mice, but not in high affinity-primed mice. Mechanistically, low affinity primed memory CD8(+) T cells produced more IL-2 and significantly upregulated IL 2Ralpha expression during rechallenge. We found that CD45RB(hi) status was also a stable marker of priming affinity within polyclonal CD8(+) T cell populations. Following high-affinity rechallenge, low affinity-primed CD45RB(hi) cells became CD45RB(lo), demonstrating that CD45RB status acts as an affinity-based differentiation switch on CD8(+) T cells. Thus, these data establish a novel mechanism by which CD45 isoforms tune low affinity-primed memory CD8(+) T cells to become potent secondary effectors following heterologous rechallenge. These findings have direct implications for allogeneic heterologous immunity by demonstrating that despite a lower precursor frequency, low-affinity priming is sufficient to generate memory cells that mediate potent secondary responses against a cross-reactive graft challenge. PMID- 26864038 TI - The Origins of Aging: Evidence that Aging is an Adaptive Phenotype. AB - BACKGROUND: Aging can be defined as the time-related decline in biological functions which ultimately results in organismal death. Beyond the stage of reproductive maturity as fertility declines, cell and tissue functions come under reduced selection pressure since organismal survival is considered no longer an evolutionary priority. Repair mechanisms become less robust and the resulting stochastic accumulation of tissue and genomic damage is believed to underlie the aging process. The objective of this review is to challenge this construct and to present evidence that aging represents a species-specific adaptive developmental program. METHODS: Through a review of published data, the cellular aging programs of both single cell and multicellular organisms are described. Since all organisms live in communities (ecosystems) of diverse species, the role of multi level selection is discussed within this context and a proposal is advanced that aging represents an adaptive phenotype. RESULTS: Single cell organisms evolved an aging phenotype in which the primary feature was replicative arrest prior to cell death. The evolution of multicellularity represented the emergence of a new level of biological organization. Multicellularity required cell-cell cooperation as well as a division of labor. In simple multicellular organisms aging was rooted in an age-related decline in stem cell function (renewal and differentiation). In complex multicellular organisms cellular aging/ death programs (senescence, autophagy, apoptosis) were used as a form of cell "altruistic" suicide carried out for the benefit of the whole organism (morphogenesis, tissue repair and maintenance). Organisms do not live in isolation. Species occupy ecological niches and communities of diverse species comprise an ecosystem. Ecosystems are highly regulated and structured biological organizations. The effective functioning and productivity of an ecosystem is determined by its biological diversity and relative species densities. Multilevel selection acts to balance optimal functioning of both the whole ecosystem and its compositional species/organisms. CONCLUSIONS: Organismal aging and death programs are adaptive; these programs provide a mechanism for regulating species population densities within the constraints imposed by the ecosystem organization. A unique feature of humans has been the development of a second inheritance system, culture. Through cultural practices, humans have expanded our ecological niche to be global in size. Our technology enriched urban ecosystem is very different from natural ecosystems. Our future evolution, including aging and lifespan, will be determined by our unique urban ecosystem through geneculture co-evolution. PMID- 26864037 TI - Subclinical Vitamin B12 Deficiency and Heart Rate Variability Across Life Cycle. AB - OBJECTIVES: The present study aimed to evaluate association between plasma vitamin B12 and heart rate variability in clusters of population of various ages across life cycle. METHODS: 47 healthy children from an ongoing pregnancy and birth cohort, 32 young adults and 47 healthy elderly subjects were recruited following inclusion and exclusion criteria. All subjects underwent plasma vitamin B12, anthropometry and heart rate variability (HRV). RESULTS: The prevalence of vitamin B12 deficiency (<148 pmol/l) across age groups were 51.1 % for children, 56.2 % for young adults and 61.7 % for the elderly group respectively. There was large variability in vitamin B12 status across the age groups. Frequency distribution of low frequency (LF) absolute units HRV in the elderly was skewed, whereas in children and young adult group there was wide distribution of LF HRV. Association between Log LF absolute units HRV and plasma vitamin B12 across groups were tested using curve fit models. In children a linear curve estimation best fitted and explained 9.3 % of the association (n=47, .=0.003, P=0.03, R2=0.09). There was no association between log LF absolute units HRV and plasma vitamin B12 in the young adult group. In the elderly group a power curve fit model best fitted and explained 8.9 % of the association. Inspection of the power curve fit model demonstrated a curvilinear pattern; there was a linear association in the elderly with vitamin B12 levels less than 200 pmol/l. However, elderly with vitamin B12 values >200 pmol/l demonstrated saturation (plateauing) of log LF HRV. CONCLUSION: The study demonstrated varied pattern of responses between vitamin B12 status and LF power of HRV across age groups. Thus, it is important to consider these associations before planning supplementation of vitamin B12. PMID- 26864039 TI - Cardiac fiber tracking using adaptive particle filtering based on tensor rotation invariant in MRI. AB - Diffusion magnetic resonance imaging (dMRI) is a non-invasive method currently available for cardiac fiber tracking. However, accurate and efficient cardiac fiber tracking is still a challenge. This paper presents a probabilistic cardiac fiber tracking method based on particle filtering. In this framework, an adaptive sampling technique is presented to describe the posterior distribution of fiber orientations by adjusting the number and status of particles according to the fractional anisotropy of diffusion. An observation model is then proposed to update the weight of particles by rotating diffusion tensor from the primary eigenvector to a given fiber orientation while keeping the shape of the tensor invariant. The results on human cardiac dMRI show that the proposed method is robust to noise and outperforms conventional streamline and particle filtering techniques. PMID- 26864041 TI - The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients. AB - Several studies have shown an association between exposure to statins and favorable clinical outcomes for various types of infections. We aimed to assess the impact of statin use on mortality, disease severity and complications among hospitalized patients with Clostridium difficile infection (CDI). Data were analyzed from a retrospectively collected database of 499 patients diagnosed with CDI during 2009-2014. We compared infection outcomes between 178 statin (36 %) users and 321 (64 %) non-users. On multivariate analysis, we found that statin use did not have a significant impact on 30-day mortality (OR = 1.54; 95 % CI, 0.85-2.79; p = 0.15) or any significant effect on CDI severity and complication. Concomitant statin use has no significant impact on short-term mortality or effect on CDI severity and complications among hospitalized patients with CDI. However, patients in the statin group were older and had higher Charlson score compared with the non-statin group. Whether these factors affected a possible impact of statins on the disease course remains to be investigated. KEY MESSAGES: * Clostridium difficile is the most common cause of infectious nosocomial diarrhea among hospitalized adult patients in the developed countries. * There is an increasing morbidity and mortality of CDI patients due to the emergence of new strains of high virulence. * Recent studies demonstrated that prior statin use has protective and ameliorating effects on morbidity and mortality among CDI patients. * Our study showed that concomitant statin use has no significant impact on short-term mortality, CDI severity and its complications. PMID- 26864040 TI - Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women. AB - This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and >=4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy. PMID- 26864042 TI - Antibiotics usage in infants during the first 18 months of life in Benin: a population-based cohort study. AB - Data centered on antibiotics usage and their determinants in African pediatric populations are limited. In order to define the determinants of antibiotics prescriptions (ABPr), we analyzed the data of a birth cohort in Benin. From 2007 to 2009, 538 infants were followed from birth to 18 months in three different health centers. The following determinants were assessed: infants' clinical findings at consultations, mothers' and children's characteristics at birth, and health parameters recorded at scheduled follow-up of general health parameters. Multilevel logistic models were performed for analysis. Among the 4394 consultations, fever represented 53.7 % of consultations, 64.1 % of which were non-malarial fevers. Antibiotics were prescribed during 44.2 % of the consultations and the proportion of ABPr differed significantly among health centers (p < 10(-3)). Nearly 40 % of ABPr were related to children without fever. During the first semester of life, the percentage of ABPr was twice lower than after (27.4 vs. 54.7, p < 10(-3)). Respiratory and enteric symptoms were positively associated with ABPr (p < 10(-3)). Malaria was significantly associated with a lower ABPr after the first semester [odds ratio (OR) = 0.55, 95 % confidence interval (CI) = 0.44-0.67, p < 10(-3)]. No maternal and child at birth characteristics were associated with ABPr. ABPr was positively associated with a low breastfeeding score (p < 10(-3)). Studies on the rational use of antibiotics in this population should give priority to children more than 6 months of age, without malaria, and with respiratory and/or enteric symptoms. Our data also advocate for studies specifically designed to assess and improve healthcare providers' compliance to guidelines on antibiotics usage. PMID- 26864043 TI - High positive predictive value of Gram stain on catheter-drawn blood samples for the diagnosis of catheter-related bloodstream infection in intensive care neonates. AB - Catheter-related bloodstream infections (CRBSIs) remain a leading cause of healthcare-associated infections in preterm infants. Rapid and accurate methods for the diagnosis of CRBSIs are needed in order to implement timely and appropriate treatment. A retrospective study was conducted during a 7-year period (2005-2012) in the neonatal intensive care unit of the University Hospital Erasme to assess the value of Gram stain on catheter-drawn blood samples (CDBS) to predict CRBSIs. Both peripheral samples and CDBS were obtained from neonates with clinically suspected CRBSI. Gram stain, automated culture and quantitative cultures on blood agar plates were performed for each sample. The paired quantitative blood culture was used as the standard to define CRBSI. Out of 397 episodes of suspected CRBSIs, 35 were confirmed by a positive ratio of quantitative culture (>5) or a colony count of CDBS culture >100 colony-forming units (CFU)/mL. All but two of the 30 patients who had a CDBS with a positive Gram stain were confirmed as having a CRBSI. Seven patients who had a CDBS with a negative Gram stain were diagnosed as CRBSI. The sensitivity, specificity, positive predictive value and negative predictive value of Gram stain on CDBS were 80, 99.4, 93.3 and 98.1 %, respectively. Gram staining on CDBS is a viable method for rapidly (<1 h) detecting CRBSI without catheter withdrawal. PMID- 26864044 TI - Comparative study of all Salmonella enterica serovar Enteritidis strains isolated from food and food animals in Greece from 2008 to 2010 with clinical isolates. AB - The aim of the present work was to study the epidemiology of Salmonella enterica serovar Enteritidis (S. Enteritidis) in Greece, comparing all the food and food animal isolates during a 3-year period with clinical isolates. Submission of the generated data to the PulseNet Europe database was carried out in order to study the population structure of this particular serovar and indicate possible connections with European strains. One hundred and sixty-eight (168) S. Enteritidis strains of human, animal, and food origin, isolated during the period 2008-2010 in Greece, were studied. Strains were characterized by phenotypic (antibiotic resistance) and molecular [pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST)] methods. PFGE revealed 39 XbaI, 48 BlnI, and 80 XbaI-BlnI distinct pulsotypes, suggesting several clones circulating through the food chain and multiple sources of transmission. Submission to the PulseNet Europe database indicated that PFGE profile SENTXB.0001, the most common PFGE profile in Europe, was also predominant in Greece (33.3 %). MLST showed that all the strains studied shared the same sequence type (ST11), representing the most common ST in Europe. High rates of resistance to nalidixic acid were observed among human and poultry isolates (~25 %), indicating the potential fluoroquinolone treatment failure. Our data suggest that strains originating from multiple reservoirs circulated in Greece through the food chain during the study period. Predominant profiles in Greece were common to PulseNet Europe profiles, indicating similarities between the S. Enteritidis populations in Greece and Europe. PMID- 26864045 TI - Bilateral practice improves dominant leg performance in long jump. AB - Benefits of bilateral practice both for the non-dominant and for the dominant body side have been shown in several studies. Thereby, most of the studies included movement tasks of the upper extremity or investigated sports games in which the ability of acting bilaterally is an essential basis for success and, thus, a bilateral practice is reasonable anyway. Individual unilaterally performed sports including movement tasks of the lower extremity are rarely investigated. Therefore, the aim of our study was to test if contralateral transfer due to bilateral practice can be found in an unilaterally performed sport including the lower extremity. We trained and tested 61 adolescent athletes in long jump to compare the jumping performance of the dominant leg after a 12 week practice period between two groups: a bilateral practice group that practiced specific long jump exercises with both the dominant and non-dominant leg and an unilateral practice group that practiced specific long jump exercises only with the dominant leg. Results showed a superior effect of bilateral practice compared to unilateral practice regarding the jumping performance of the dominant leg. The performance increase at post-test and retention-test for the dominant limb was significantly higher for the bilateral practice group (pre-to post: 5.2%, pre-to-retention: 7.4%) compared to the unilateral practice group (pre-to-post: 3.4%, pre-to-retention: 4.5%). Thus, bilateral practice should be established in the early practice programmes of track and field athletes to improve the performance of the dominant take-off leg. PMID- 26864046 TI - A novel homozygous MYO7A mutation involved in a Venezuelan population with high frequency of USHER1B. AB - BACKGROUND: Macanao's population in Venezuela has perhaps the greatest incidence of USH1B known in Latin America (79 cases per 100,000 population); however, until now no mutation in the MYO7A gene had been reported for this population. MATERIALS AND METHODS: This study aimed to evaluate the entire coding region of the MYO7A gene by direct sequencing of PCR products obtained from patients clinically diagnosed with USH1B. RESULTS: A novel mutation named c.6079_6081del was detected on exon 45 of the MYO7A gene, causing the loss of a single histidine amino acid at codon 2027 (p.H2027del) located within the second FERM domain of the human protein myosin VIIA. Three patients with clinical diagnosis of USH1B were detected positive in homozygosis for the c.6079_6081del mutation; whereas six people from the same affected family were heterozygotes and three other family members were negative. CONCLUSION: We suggest that this new mutation named c.6079_6081del (p.H2027del) is the main cause of deaf-blindness found in this family clinically diagnosed as USH1B. Additional studies should be performed on this population to determine whether the c.6079_6081del mutation is the main cause of USH1B for the rest of the population. PMID- 26864047 TI - Clinical and pathophysiological issues associated with type 1 autoimmune pancreatitis. AB - In 1995, Yoshida and colleagues proposed the concept of 'autoimmune pancreatitis' (AIP). Recently, it is accepted that the existence of two subtypes of AIP-type 1, which involves immunoglobulin G4 (IgG4) as the pancreatic manifestation of IgG4 related disease (IgG4-RD), and type 2, which is characterized by granulocytic epithelial lesions. Type 2 AIP is thought to be rare in Japan. In 2011, the International Consensus Diagnostic Criteria (ICDC) for autoimmune pancreatitis was proposed. In Japan, the clinical diagnostic criteria of AIP 2011 was proposed by the Japan Pancreas Society (JPS) and the Research Committee of Intractable Diseases of the Pancreas. The JPS 2011 is based on ICDC and a simplified checklist of items to diagnose type 1 AIP. Although recent progress in type 1 AIP has resolved clinical features, diagnosis, treatment, and pathogenesis, many clinical and basic issues still remain unclear. Here, we provide an overview of the recent clinical and basic issues associated with type 1 AIP. PMID- 26864048 TI - Setup accuracy for prone and supine whole breast irradiation. AB - PURPOSE: To evaluate cone-beam computed tomography (CBCT) based setup accuracy and margins for prone and supine whole breast irradiation (WBI). METHODS: Setup accuracy was evaluated on 3559 CBCT scans of 242 patients treated with WBI and uncertainty margins were calculated using the van Herk formula. Uni- and multivariate analysis on individual margins was performed for age, body mass index (BMI) and cup size. RESULTS: The population-based margin in vertical (VE), lateral (LA) and longitudinal (LO) directions was 10.4/9.4/9.4 mm for the 103 supine and 10.5/22.4/13.7 mm for the 139 prone treated patients, being significantly (p < 0.01) different for the LA and LO directions. Multivariate analysis identified a significant (p < 0.05) correlation between BMI and the LO margin in supine position and the VE/LA margin in prone position. CONCLUSION: In this series, setup accuracy is significantly worse in prone compared to supine position for the LA and LO directions. However, without proper image-guidance, uncertainty margins of about 1 cm are also necessary for supine WBI. For patients with a higher BMI, larger margins are required. PMID- 26864049 TI - Towards clinical implementation of ultrafast combined kV-MV CBCT for IGRT of lung cancer : Evaluation of registration accuracy based on phantom study. AB - PURPOSE: Combined kV-MV cone-beam CT (CBCT) is a promising approach to accelerate imaging for patients with lung tumors treated with deep inspiration breath-hold. During a single breath-hold (15 s), a 3D kV-MV CBCT can be acquired, thus minimizing motion artifacts and increasing patient comfort. Prior to clinical implementation, positioning accuracy was evaluated and compared to clinically established imaging techniques. METHODS AND MATERIALS: An inhomogeneous thorax phantom with four tumor-mimicking inlays was imaged in 10 predefined positions and registered to a planning CT. Novel kV-MV CBCT imaging (90 degrees arc) was compared to clinically established kV-chest CBCT (360 degrees ) as well as nonclinical kV-CBCT and low-dose MV-CBCT (each 180 degrees ). Manual registration, automatic registration provided by the manufacturer and an additional in-house developed manufacturer-independent framework based on the MATLAB registration toolkit were applied. RESULTS: Systematic setup error was reduced to 0.05 mm by high-precision phantom positioning with optical tracking. Stochastic mean displacement errors were 0.5 +/- 0.3 mm in right-left, 0.4 +/- 0.4 mm in anteroposterior and 0.0 +/- 0.4 mm in craniocaudal directions for kV-MV CBCT with manual registration (maximum errors of no more than 1.4 mm). Clinical kV-chest CBCT resulted in mean errors of 0.2 mm (other modalities: 0.4-0.8 mm). Similar results were achieved with both automatic registration methods. CONCLUSION: The comparison study of repositioning accuracy between novel kV-MV CBCT and clinically established volume imaging demonstrated that registration accuracy is maintained below 1 mm. Since imaging time is reduced to one breath hold, kV-MV CBCT is ideal for image guidance, e.g., in lung stereotactic ablative radiotherapy. PMID- 26864051 TI - Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats. AB - Kidney injury is a deleterious side effect accompanied by therapeutic uses of cisplatin as an antineoplastic agent. However, no therapeutic option is available against this complication. This study was designed to evaluate the protective role of a glycoprotein extract obtained from Eisenia foetida against cisplatin induced nephrotoxicity. Rats were treated with cisplatin (7.5 mg/kg, intraperitoneally, i.p.) and Eisenia foetida extract (300 and 500 mg/kg, i.p. and/or oral). Serum creatinine (Cr) and blood urea nitrogen (BUN) were significantly elevated in cisplatin-treated rats. A significant amount of lipid peroxidation was detected in drug-treated animals. Furthermore, kidney histopathological findings revealed acute tubular necrosis and hyaline cast formation caused by cisplatin. Eisenia foetida extract administration (300 and 500 mg/kg, i.p.) significantly reduced serum BUN and creatinine and lipid peroxidation in kidney tissue. Moreover, cisplatin-induced histopathological lesions were alleviated by Eisenia foetida extract. This investigation concluded that Eisenia foetida extract ameliorated cisplatin-induced nephrotoxicity. This protection might be mediated by preventing cisplatin-induced oxidative stress. PMID- 26864050 TI - DC generation from peripheral blood mononuclear cells in patients with chronic myeloid leukemia: Influence of interferons on DC yield and functional properties. AB - In Chronic Myeloid Leukemia (CML), standard treatment consists of modern tyrosine kinase inhibitors (TKI). Nevertheless, there is evidence that immune responses against leukemia-associated antigens (LAA) may play an important role in disease control. Dendritic cell (DC)- based immunotherapy is able to induce T cell responses against LAA and might therefore pose an interesting therapeutic option in CML, especially in the setting of minimal residual disease (MRD). GMP production of DC for clinical vaccination remains a time- and cost- intensive procedure and standardized DC generation is warranted. We asked whether maturation-induction with IFN-gamma and IFN-alpha has an influence on functional properties of DC derived from peripheral blood mononuclear cells (PBMC) in CML patients. Monocyte-derived DC from healthy donors and from patients with CML were analyzed after maturation-induction with our TNF-alpha-containing standard cytokine cocktail with or without addition of IFN-alpha and/or IFN-gamma. Our results confirm that the addition of IFN-gamma leads to enhanced IL-12 secretion in healthy donors. In contrast, in CML patients, IFN-gamma was not able to increase IL-12 secretion, possibly due to a higher degree of cell adherence and lower cell yield during the cell culture. Our data suggest, that- in contrast to healthy donors-, additional interferons are not beneficial for maturation induction during large-scale DC production in patients with CML. PMID- 26864052 TI - Evaluative ratings and attention across the life span: emotional arousal and gender. AB - This study was designed to investigate the evolution of emotional processing over the whole adult life span as a function of stimulus arousal and participants' gender. To this end, self-reported affective evaluation and attentional capture prompted by pleasant and unpleasant pictures varying in arousal were measured in a large sample of participants (n = 211) balanced by gender and equally spread across seven decades from 20 to 90 years. Results showed age differences only for affective evaluation of pleasant stimuli, with opposite patterns depending on stimulus arousal. As age increased, low-arousing pleasant cues (e.g. images of babies) were experienced as more pleasant and arousing by both males and females, whereas high-arousing stimuli (e.g. erotic images) were experienced as less pleasant only by females. In contrast, emotional pictures (both pleasant and unpleasant) were effective at capturing attention in a similar way across participants, regardless of age and gender. Taken together, these findings suggest that specific emotional cues prompt different subjective responses across different age groups, while basic mechanisms involved in attentional engagement towards both pleasant and unpleasant stimuli are preserved in healthy ageing. PMID- 26864053 TI - HIV risk behavior and internalizing/externalizing psychopathology among adolescents in court-ordered treatment. AB - BACKGROUND: The confluence of drug use behaviors, sexual risk, and psychopathology may complicate human immunodeficiency virus (HIV) prevention intervention for adolescents engaging in substance use and criminal behavior. However, few studies have examined these risk associations. OBJECTIVE: This study identified HIV risk behavior subgroups among adolescents in court-ordered substance abuse treatment and examined linkages with dimensions of internalizing and externalizing psychopathology. METHODS: Internalizing and externalizing behaviors were assessed with the Millon Adolescent Clinical Inventory (MACI). Latent class analysis was used to identify subgroups on the basis of involvement in substance use proximal to sex, number of partners, and consistency of condom use. RESULTS: Participants (n = 301) were identified as demonstrating high, medium, or low levels of sexual risk behavior. Greater externalizing psychopathology distinguished the high risk class from the medium risk class and from the low risk class. CONCLUSION: Detained youth with particularly serious oppositional-defiant behavioral characteristics, substance use, and sex risk behavior likely require intensive interventions that address the multiple systemic factors that contribute to the development and maintenance of this pattern. PMID- 26864055 TI - Novel investigational vascular endothelial growth factor (VEGF) receptor antagonists for psoriasis. AB - INTRODUCTION: Affecting 1 million people in the UK, psoriasis is a commonly diagnosed inflammatory disease arising from autoimmune processes that are triggered by environmental factors in genetically susceptible individuals. The pathophysiology of psoriasis has been widely studied and there is evidence that angiogenesis is a key component. AREAS COVERED: In this review the role of vascular endothelial growth factor-A (VEGF), as a key angiogenic mediator in psoriasis pathogenesis is discussed. VEGF is found in higher levels in plaques, normal skin and plasma of patients with psoriasis. The level of VEGF also fluctuates in accordance with disease activity and in response to conventional treatments. There are several VEGF inhibitors currently licenced for use; primarily in the fields of oncology and there are case reports of patients being treated with these therapies for metastatic cancer who have demonstrated significant improvement in their psoriasis. VEGF inhibitory agents have suggested promising utility for the treatment of psoriasis following animal studies. EXPERT OPINION: VEGF may represent a novel treatment target in psoriasis. However, VEGF inhibitors can cause significant side effects such as hypertension and left ventricular dysfunction. The risks of treatment must be carefully evaluated before VEGF inhibitors are trialled or advocated for psoriasis. PMID- 26864054 TI - Imaging genomics in cancer research: limitations and promises. AB - Recently, radiogenomics or imaging genomics has emerged as a novel high throughput method of associating imaging features with genomic data. Radiogenomics has the potential to provide comprehensive intratumour, intertumour and peritumour information non-invasively. This review article summarizes the current state of radiogenomic research in tumour characterization, discusses some of its limitations and promises and projects its future directions. Semi radiogenomic studies that relate specific gene expressions to imaging features will also be briefly reviewed. PMID- 26864057 TI - Does core stability exercise improve lumbopelvic stability (through endurance tests) more than general exercise in chronic low back pain? A quasi-randomized controlled trial. AB - INTRODUCTION: The aim was to compare core stability and general exercises (GEs) in chronic low back pain (LBP) patients based on lumbopelvic stability (LPS) assessment through three endurance core stability tests. There is a controversy about preference of core stability exercise (CSE) over other types of exercise for chronic LBP. Studies which have compared these exercises used other outcomes than those related to LPS. As it is claimed that CSE enhances back stability, endurance tests for LPS were used. MATERIALS AND METHODS: A 16-session CSE program and a GE program with the same duration were conducted for two groups of participants. Frequency of interventions for both groups was three times a week. Forty-three people (aged 18-60 years) with chronic non-specific LBP were alternately allocated to core stability (n = 22) or GE group (n = 21) when admitted. The primary outcomes were three endurance core stability tests including: (1) trunk flexor; (2) trunk extensor; and (3) side bridge tests. Secondary outcomes were disability and pain. Measurements were taken at baseline and the end of the intervention. RESULTS: After the intervention, test times increased and disability and pain decreased within groups. There was no significant difference between two groups in increasing test times (p = 0.23 to p = 0.36) or decreasing disability (p = 0.16) and pain (p = 0.73). CONCLUSIONS: CSE is not more effective than GE for improving endurance core stability tests and reducing disability and pain in chronic non-specific LBP patients. PMID- 26864056 TI - Piloting a new approach in primary care to identify, assess and support carers of people with terminal illnesses: a feasibility study. AB - BACKGROUND: General practices in the United Kingdom are encouraged to have a protocol for the identification of carers and a mechanism for social care referral. However, a minority of carers are identified and those caring for someone with a terminal illness often cope until the situation becomes overwhelming. Earlier identification could enable more timely support. The aim of this project was to model and pilot a systematic approach to identify, assess and support carers of people with supportive and palliative care needs in primary care. METHOD: The intervention was modelled on the Medical Research Council complex intervention framework with a preliminary theoretical phase, which has been reported elsewhere. In this study, which lasted 12 months, four general practices were recruited. Each practice identified a 'carer liaison' person to take the lead in identifying carers, followed by assessment and support using a toolkit modelled from the earlier phase. Qualitative evaluation interviews were conducted with carers who had received the intervention and the carer liaisons and general practitioners in the pilot practices. A stakeholder event was held to disseminate and deliberate the findings. RESULTS: The practices' populations ranged from 5840 to 10832 patients and across the four practices, 83 carers were identified. Thirty six carers were identified from practice registers (disease - 16; palliative care - 9; carer - 11; advanced care plan - 12), whilst 28 were identified opportunistically by practice staff at appointments or at home. Seven carers self-identified. Overall, 81 carers received the carer pack and 25 returned the Carer Support Needs Assessment Tool (CSNAT) form. Eleven carers received a follow up call from the practice to discuss support and 12 were also referred/signposted for support. Qualitative interviews suggest carers valued connection with their practices but the paperwork in the toolkit was onerous. CONCLUSION: This approach to identifying and supporting carers was acceptable, but success was dependent on engagement within the whole practice. Carers did not tend to self-identify, nor ask for help. Practices need to proactively identify carers using existing opportunities, resources and computer systems, and also adopt a public health approach to raise carer awareness and perceived support within their communities. PMID- 26864059 TI - [Hairy roots culture as a source of valuable biopharmaceuticals]. AB - Plants have been exploited as a source of medicinal substances for years. Nowadays, achievements of modern science, including molecular biotechnology, allow their huge potential to be utilized. They have become a promising platform for the production of valuable compounds such as biopharmaceuticals. Among the various plant systems used for this purpose, hairy root cultures are also applied for the production of recombinant proteins and secondary metabolites. For this purpose plant cells of selected species are genetically transformed using different strains of Agrobacterium rhizogenes carrying the desired genes. The next steps of this process include stable and efficient expression of these genes. Hairy root cultures exhibit a number of features which make them attractive compared to various pro- and eukaryotic cell systems including other plant models. Their main advantages are: relatively low production costs, ease of scale-up, production of compounds typical for eukaryotic cells with post translational modifications, biological safety, and in many cases there is no need for complex purification techniques of the final product. Several compounds that are successfully obtained using this production strategy are valuable pharmaceuticals. This group includes selected cytokines, vaccine antigens and antibodies. PMID- 26864058 TI - Biodistribution and toxicity of radio-labeled few layer graphene in mice after intratracheal instillation. AB - BACKGROUND: The potential human health risks from graphene inhalation exposure have attracted substantial scientific interest as a result of the numerous exciting potential commercial applications of graphene. However, the long-term distribution of graphene in organisms after inhalation is unknown, largely as a result of challenges associated with accurate graphene quantification. METHODS: Carbon-14 labeled FLG was used to quantify the in vivo distribution of FLG in mice after oral gavage or intratracheal instillation for up to 3 or 28 days after exposure, respectively. RESULTS: Intratracheally instilled FLG was mainly retained in the lung with 47% remaining after 4 weeks. Exposure to non-labeled FLG resulted in dose-dependent acute lung injury and pulmonary edema, but these effects were alleviated with time despite the continued presence of FLG in the lungs. One percent and 0.18% of the intratracheally instilled FLG was present in the liver and spleen, respectively, after 14 days by passing through the air blood barrier, a finding supported by the results of oral gavage experiments which did not show detectable absorption through the gastrointestinal tract. In addition, 46.2% of the intratracheally instilled FLG was excreted through the feces 28 d after exposure. CONCLUSIONS: Quantitative measurements revealed the elimination mechanism for FLG and its biodistribution for two exposure pathways. Graphene persistence in the lung only caused transient pulmonary effects. The in vivo distribution, elimination, and toxicity results provided here measured using a robust quantitative method support the human health risk assessment of graphene. PMID- 26864060 TI - Disease duration and age influence CARD15 expression in Crohn's disease. AB - One of the susceptibility genes in Crohn's disease (CD) is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) with E.Z.N.A. Total RNA Kit (Omega Bio-tek) then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR) and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFalpha agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn>s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression. PMID- 26864061 TI - [MAVS protein and its interactions with hepatitis A, B and C viruses]. AB - Mitochondrial antiviral signaling protein (MAVS) transmits activation signal of type I interferon (IFN) gene transcription in the molecular intracellular pathway, which depends on the protein encoded by retinoic acid inducible gene I (RIG-I) or melanoma differentiation-associated protein-5 (MDA-5). MAVS, as a signal molecule, performs an essential function in the development of an antiviral immune response. The molecule of MAVS consists of two domains: the N terminal domain and the C-terminal domain. The N-terminal end of MAVS contains the caspase activation and recruitment domain (CARD). CARD is responsible for MAVS interaction with RIG-I and MDA-5, which act as cytosolic sensors detecting foreign viral genetic material in the host cell. After binding to viral RNA, RIG I or MDA-5 activates MAVS and transmits the signal of IFN type I gene expression. The C-terminal transmembrane domain (TM) of MAVS anchors the protein to the outer mitochondrial membrane. In this paper interactions between MAVS and hepatitis virus type A (HAV), type B (HBV) and type C (HCV) are presented. Mechanisms of indirect activation of MAVS by viral DNA and RNA, as well as the strategies of HAV, HBV and HCV for blocking of the intracellular signaling pathway at the level of MAVS, are described. PMID- 26864062 TI - [Immune checkpoint-targeted cancer immunotherapies]. AB - Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system. Their blockade would overcome immune tolerance in the tumor microenvironment and amplify antitumor immunity. What's more, immune checkpoint blockade may turn out even more profitable, as some of immune checkpoints and their ligands are expressed on tumor surface and on tumor infiltrating lymphocytes, contributing to the immunosuppressive cancer microenvironment. Phase III clinical trials have confirmed efficacy of an anti-CTLA-4 antibody ipilimumab, thereby leading to its acceptance for the treatment of advanced melanoma. Thanks to promising results of the phase I clinical trials, a breakthrough therapy designation and an early approval for the treatment have been granted to anti-PD-1 antibodies - nivolumab (for the treatment of advanced melanoma and advanced non-small cell lung cancer) and pembrolizumab (for the treatment of advanced melanoma) and, in the treatment of advanced bladder cancer, an anti-PD-L1 antibody - MPDL3280A as well. Other immune checkpoints, such as LAG 3, TIM-3, BTLA, B7-H3 and B7-H4, are also under early evaluation. PMID- 26864063 TI - [The latest recommendations on the use of new oral anticoagulants in routine practice]. AB - The use of non-vitamin K antagonist oral anticoagulants (NOACs) has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC) including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice. PMID- 26864064 TI - Inflammation markers are associated with metabolic syndrome and ventricular arrhythmia in patients with coronary artery disease. AB - BACKGROUND: Inflammation plays a major role in the development and progression of atherosclerosis and coronary artery disease (CAD). Inflammation markers, including white blood cell (WBC) count, C-reactive protein (CRP) and interleukin 6 (IL-6), are widely used for cardiovascular risk prediction. The aim of the study was to establish factors associated with WBC, CRP and IL-6 in patients with CAD. Two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism were analyzed (C34T AMPD1, G22A ADA). METHODS: Plasma concentrations of IL-6 were measured using high-sensitivity ELISA kits, and the nephelometric method was used for high-sensitivity CRP (hs-CRP) measurement in 167 CAD patients. RESULTS: Presence of metabolic syndrome (MS) and its components, presence of heart failure, severity of CAD symptoms, severe past ventricular arrhythmia (sustained ventricular tachycardia [sVT] or ventricular fibrillation [VF]), lower left ventricle ejection fraction, higher left ventricle mass index, higher end-diastolic volume and higher number of smoking pack-years were significantly associated with higher WBC, CRP and IL-6. Strong associations with arrhythmia were observed for IL-6 (median 3.90 vs 1.89 pg/mL, p<0.00001) and CRP concentration (6.32 vs 1.47 mg/L, p=0.00009), while MS was associated most strongly with IL-6. CRP and IL-6 were independent markers discriminating patients with sVT or VF. There were no associations between AMPD1 or ADA genotypes and inflammation markers. CONCLUSIONS: WBC, CRP and IL-6 are strongly associated with components of the metabolic syndrome. Their strong association with life threatening ventricular arrhythmia emphasizes the proarrhythmic role of inflammation in the increased cardiovascular risk of CAD patients. PMID- 26864065 TI - [The importance of ADAM family proteins in malignant tumors]. AB - Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor alpha (TNFalpha) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients. PMID- 26864066 TI - Effect of methylprednisolone, hyaluronic acid and pioglitazone on histological remodeling of temporomandibular joint cartilage in rabbits affected by drug induced osteoarthritis. AB - BACKGROUND: The aims of this study were to assess the anti-degenerative effects of pioglitazone and to compare these effects with those of methylprednisolone and hyaluronic acid on drug-induced osteoarthritis in rabbits' temporomandibular joint cartilage. MATERIAL AND METHODS: The experiment was conducted on 40 Californian white rabbits. Degenerative changes were induced by intra-articular injections of papain. Subsequently, all of the animals were randomly assigned to one of four groups: 1) a control group that received no medications; 2) a group treated with 4 intra-articular injections of 2 mg (0.2 ml) of hyaluronic acid at weekly intervals; 3) a group treated with 4 intra-articular injections of 2 mg (0.1 ml) of methylprednisolone at weekly intervals; 4) a group administered pioglitazone orally in daily doses of 2 mg/kg of body weight. Four weeks after the beginning of drug administration, the rabbits were sacrificed. Sagittal sections of the intra-articular cartilage (discs) and mandibular condyles were stained with hematoxylin and eosin by the PAS technique and with van Gieson's solution. Histologic examinations, as well as cartilage thickness and number of cell layers measurements, were performed. RESULTS: Histologic assessment in cases of arthritis-associated pathologies revealed that changes occurred most frequently in the control group and least frequently in the pioglitazone group. There were no differences in the histological structures of the intra-articular discs. Cartilage thickness measurements demonstrated the thinnest cartilage in group 2 and the thickest in group 3. Analysis of cell layer numbers showed the most numerous layers in the pioglitazone group and the least in the control group. CONCLUSION: Pioglitazone and hyaluronic acid showed anti-degenerative properties compared to methylprednisolone in an animal model. PMID- 26864067 TI - 786T/c endothelial nitric oxide synthase gene polymorphism and coronary collateral circulation. AB - INTRODUCTION: In this study, we investigated the association between -786T/C polymorphism of the endothelial nitric oxide (NOS3) gene in which thymidine is replaced by a cytosine at nucleotide -786 (rs 2070744) and coronary collateral circulation (CCC) in patients with stable coronary artery disease. MATERIALS AND METHODS: 286 patients having a critical stenosis (> 95%) in at least one major epicardial coronary vessel were included in the study. CCC was defined according to the Rentrop classification (R). Patients with R0-1 CCC were included in the poor CCC group and subjects with R2-3 CCC were assigned to the good CCC group. The polymerase chain reaction method was used for genotyping. 152 patients with poor CCC and 134 patients with good CCC were examined. RESULTS: The frequency of cytosine-cytosine (CC) and thymidine-cytosine (TC) genotypes and allele C were higher in the poor CCC group, but the difference did not reach statistical significance. In the dominant model, the frequency of CC+TC vs. thymidine thymidine (TT) genotypes was significantly higher in the poor CCC group (67.1% vs. 54.5%, respectively; chi2=4.78; p=0.02). In multivariate regression analysis, the dominant model for -786T/C polymorphism of the NOS3 gene remained as an independent correlate of poor CCC. DISCUSSION: -786T/C polymorphism of the NOS3 gene (rs 2070744) may be associated with poor angiogenesis and the development of CCC in stable coronary artery disease. PMID- 26864068 TI - Clinical Experience With n-Butyl-2-Cyanoacrylate in Performing Lateral Neck Dissection for Metastatic Thyroid Cancer. AB - Background Chyle leakage following lateral neck dissection (LND) is rare, but can induce metabolic disturbances, delay wound healing, and prolong hospitalization. n-Butyl-2-cyanoacrylate (NBCA) has been used to achieve hemostasis and seal tissues in several surgical settings. We here assessed whether application of NBCA to the thoracic duct area is effective in sealing chyle leakage. Methods The medical records of 163 patients who underwent total thyroidectomy with unilateral LND between March 2011 and September 2012 were reviewed. NBCA was applied to 84 patients and not applied to 79. Drainage volume, duration of hospital stay, and incidence of complications were compared between the 2 groups. Results The 2 groups were not different with regard to age, body weight, gender, primary tumor histology, and number of lateral neck nodes harvested. Mean hospital stay was significantly shorter (4.3 +/- 1.8 vs 5.7 +/- 3.0 days, P < .001), median total drainage volume was significantly smaller (270 mL; range: 97-931 mL vs 328 mL; range: 113-2636 mL; P < .001), and rate of chyle leakage was significantly lower (0% vs 6.3%, P = .025) in the NBCA than in the non-NBCA group. Conclusion NBCA application to the dissected area of the thoracic duct posterior to its angle of junction with the internal jugular and subclavian veins could be safe and effective in reducing surgical complications related to chyle leakage after LND. PMID- 26864069 TI - Painless, gradually enlarging, subcutaneous lesion of the eyelid. PMID- 26864070 TI - Effect of temperature and relative humidity on the development times and survival of Synopsyllus fonquerniei and Xenopsylla cheopis, the flea vectors of plague in Madagascar. AB - BACKGROUND: Plague, a zoonosis caused by Yersinia pestis, is found in Asia, the Americas but mainly in Africa, with the island of Madagascar reporting almost one third of human cases worldwide. In the highlands of Madagascar, plague is transmitted predominantly by two flea species which coexist on the island, but differ in their distribution. The endemic flea, Synopsyllus fonquerniei, dominates flea communities on rats caught outdoors, while the cosmopolitan flea, Xenopsylla cheopis, is found mostly on rats caught in houses. Additionally S. fonquerniei seems restricted to areas above 800 m. Climatic constraints on the development of the two main vectors of plague could explain the differences in their distribution and the seasonal changes in their abundance. Here we present the first study on effects of temperature and relative humidity on the immature stages of both vector species. METHODS: We examined the two species' temperature and humidity requirements under experimental conditions at five different temperatures and two relative humidities. By employing multivariate and survival analysis we established the impact of temperature and relative humidity on development times and survival for both species. Using degree-day analysis we then predicted the average developmental threshold for larvae to reach pupation and for pupae to complete development under each treatment. This analysis was undertaken separately for the two relative humidities and for the two species. RESULTS: Development times and time to death differed significantly, with the endemic S. fonquerniei taking on average 1.79 times longer to complete development and having a shorter time to death than X. cheopis under adverse conditions with high temperature and low humidity. Temperature had a significant effect on the development times of flea larvae and pupae. While humidity did not affect the development times of either species, it did influence the time of death of S. fonquerniei. Using degree-day analysis we estimated an average developmental threshold of 9 degrees C for S. fonquerniei, and 12.5 degrees C for X. cheopis. CONCLUSIONS: While many vector-borne diseases are limited to warm, low-lying regions, plague in Madagascar is unusual in being most prevalent in the cool, highland regions of the country. Our results point towards the possibility that this is because the endemic flea vector, S. fonquerniei, is better adapted to cool temperatures than the exotic flea vector, X. cheopis. Future warming caused by climate change might reduce the area suitable for S. fonquerniei and may thus reduce the incidence of plague in Madagascar. PMID- 26864071 TI - Work-related musculoskeletal disorders and ergonomic risk factors in special education teachers and teacher's aides. AB - BACKGROUND: Work-related musculoskeletal disorders (WMSDs) have become increasingly common among health-related professionals. Special education personnel who serve students with disabilities often experience physical strains; however, WMSDs have been overlooked in this population. The objectives of this study were to investigate the work-related ergonomics-associated factors in this population and to evaluate their correlation with the WMSDs prevalence. METHODS: A questionnaire with three domains, namely demographics, prevalence of work related musculoskeletal disorders, and ergonomic factors, designed by our research team was delivered to educators who work in special education schools. RESULTS: Approximately 86 % of the 388 special education school teachers and teacher's aides in this study experienced musculoskeletal disorders. The lower back, shoulder, and wrist were the three most affected regions. A logistic regression analysis revealed that the participants' background factors, namely >5.5 years of experience (odds ratio [OR] = 4.090, 95 % CI: 1.350-12.390), students with multiple disorders (OR = 2.412, 95 % CI: 1.100-5.287), and other work-related ergonomic factors (assistance in diaper changing and others duties), were strongly associated with the prevalence of WMSD. Nap habit (OR = 0.442, 95 % CI: 0.230-0.851) and having teaching partners in the same class (OR = 0.486, 95 % CI: 0.250-0.945) resulted in low possibility of acquiring WMSDs. The use of supportive devices was associated with a low WMSD prevalence. CONCLUSIONS: The present study revealed an association between WMSDs and specific job features among teachers and teacher's aides in special education schools. Future efforts should emphasize examining safe student-handling ergonomics, formulating policies regarding student-teacher ratio, incorporating mandatory break times at the workplaces, and promoting personal health for preventing work-related injuries. PMID- 26864072 TI - Integrative modeling of multi-omics data to identify cancer drivers and infer patient-specific gene activity. AB - BACKGROUND: High throughput technologies have been used to profile genes in multiple different dimensions, such as genetic variation, copy number, gene and protein expression, epigenetics, metabolomics. Computational analyses often treat these different data types as independent, leading to an explosion in the number of features making studies under-powered and more importantly do not provide a comprehensive view of the gene's state. We sought to infer gene activity by integrating different dimensions using biological knowledge of oncogenes and tumor suppressors. RESULTS: This paper proposes an integrative model of oncogene and tumor suppressor activity in cells which is used to identify cancer drivers and compute patient-specific gene activity scores. We have developed a Fuzzy Logic Modeling (FLM) framework to incorporate biological knowledge with multi omics data such as somatic mutation, gene expression and copy number measurements. The advantage of using a fuzzy logic approach is to abstract meaningful biological rules from low-level numerical data. Biological knowledge is often qualitative, thus combining it with quantitative numerical measurements may leverage new biological insights about a gene's state. We show that the oncogenic and altered tumor suppressing state of a gene can be better characterized by integrating different molecular measurements with biological knowledge than by each data type alone. We validate the gene activity score using data from the Cancer Cell Line Encyclopedia and drug sensitivity data for five compounds: BYL719 (PIK3CA inhibitor), PLX4720 (BRAF inhibitor), AZD6244 (MEK inhibitor), Erlotinib (EGFR inhibitor), and Nutlin-3 (MDM2 inhibitor). The integrative score improves prediction of drug sensitivity for the known drug targets of these compounds compared to each data type alone. The gene activity scores are also used to cluster colorectal cancer cell lines. Two subtypes of CRCs were found and potential cancer drivers and therapeutic targets for each of the subtypes were identified. CONCLUSIONS: We propose a fuzzy logic based approach to infer gene activity in cancer by integrating numerical data with descriptive biological knowledge. We compute general patient-specific gene-level scores useful to determine the oncogenic or tumor suppressor status of cancer gene drivers and to cluster or classify patients. PMID- 26864073 TI - Sleeping in on pancreatic cancer pain: Schwann cell secreted IL-6 pushes snooze on the pain alarm. PMID- 26864074 TI - Exploring psychiatry through images and objects. PMID- 26864076 TI - Alpha-synuclein: relating metals to structure, function and inhibition. AB - Alpha-synuclein has long been studied due to its involvement in the progression of Parkinson's disease (PD), a common neurodegenerative disorder, although a consensus on the exact function of this protein is elusive. This protein shows remarkable structural plasticity and this property is important for both correct cellular function and pathological progression of PD. Formation of intracellular oligomeric species within the substantia nigra correlates with disease progression and it has been proposed that formation of a partially folded intermediate is key to the initiation of the fibrillisation process. Many factors can influence changes in the structure of alpha-synuclein such as disease mutations and interaction with metals and neurotransmitters. High concentrations of both dopamine and metals are present in the substantia nigra making this an ideal location for both the structural alteration of alpha-synuclein and the production of toxic oxygen species. The recent proposal that alpha-synuclein is a ferrireductase is important as it can possibly catalyse the formation of such reactive species and as a result exacerbate neurodegeneration. PMID- 26864075 TI - Aptamers in analytics. AB - Nucleic acid aptamers are promising alternatives to antibodies in analytics. They are generally obtained through an iterative SELEX protocol that enriches a population of synthetic oligonucleotides to a subset that can recognize the chosen target molecule specifically and avidly. A wide range of targets is recognized by aptamers. Once identified and optimized for performance, aptamers can be reproducibly synthesized and offer other key features, like small size, low cost, sensitivity, specificity, rapid response, stability, and reusability. This makes them excellent options for sensory units in a variety of analytical platforms including those with electrochemical, optical, and mass sensitive transduction detection. Many novel sensing strategies have been developed by rational design to take advantage of the tendency of aptamers to undergo conformational changes upon target/analyte binding and employing the principles of base complementarity that can drive the nucleic acid structure. Despite their many advantages over antibodies, surprisingly few aptamers have yet been integrated into commercially available analytical devices. In this review, we discuss how to select and engineer aptamers for their identified application(s), some of the challenges faced in developing aptamers for analytics and many examples of their reported successful performance as sensors in a variety of analytical platforms. PMID- 26864077 TI - Sequential processing of mannose-containing glycans by two alpha-mannosidases from Solitalea canadensis. AB - Two putative alpha-mannosidase genes isolated from the rather unexplored soil bacterium Solitalea canadensis were cloned and biochemically characterised. Both recombinant enzymes were highly selective in releasing alpha-linked mannose but no other sugars. The alpha-mannosidases were designated Sca2/3Man2693 and Sca6Man4191, and showed the following biochemical properties: the temperature optimum for both enzymes was 37 degrees C, and their pH optima lay at 5.0 and 5.5, respectively. The activity of Sca2/3Man2693 was found to be dependent on Ca(2+) ions, whereas Cu(2+) and Zn(2+) ions almost completely inhibited both alpha-mannosidases. Specificity screens with various substrates revealed that Sca2/3Man2693 could release both alpha1-2- and alpha1-3-linked mannose, whereas Sca6Man4191 only released alpha1-6-linked mannose. The combined enzymatic action of both recombinant alpha-mannosidases allowed the sequential degradation of high mannose-type N-glycans. The facile expression and purification procedures in combination with strict substrate specificities make alpha-mannosidases from S. canadensis promising candidates for bioanalytical applications. PMID- 26864079 TI - Squamous Cell Cancer of Unknown Primary and Primary Breast Cancer in an HIV Infected Woman: The Importance of Cancer Screening for People Living with HIV/AIDS. AB - People living with HIV/AIDS (PLWHA) are surviving longer, with an increased risk of cancer. Cancer screening strategies in PLWHA are lacking. We describe the case of a woman with a history of AIDS, who had a nondetectable viral load on treatment. She is an activist, promoting HIV care, but had not undergone routine screening for breast, cervical, or colonic neoplasia. She presented with a left groin mass, which on biopsy proved to be a p16 immuno-histochemical positive squamous cell carcinoma. Anal and cervicovaginal examinations did not show invasive cancer, although high-resolution anoscopy identified high-grade anal dysplasia. A mammogram followed by magnetic resonance imaging showed invasive ductal carcinoma. Her breast cancer was treated with lumpectomy, adjuvant brachytherapy and chemotherapy. The left groin tumor was treated with chemo radiation. Herein, we also review medical literature concerning anal, cervical, breast, colorectal, and lung cancer screening for PLWHA, which is important for our aging population of PLWHA. PMID- 26864080 TI - Dynamics of intramolecular spin exchange interaction of a nitronyl nitroxide diradical in solution and on surfaces. AB - In this paper we report the study of the dynamics of a thermally modulated intramolecular spin exchange interaction of a novel diradical nitronyl nitroxide substituted disulfide in solution and when it is grafted on a gold surface. The structure of this diradical was designed to have flexible chains leading to intramolecular collisions and hence spin exchange interaction, and with an appropriate binding group to be grafted on the gold surface to study its behavior on the surface. In solution, this diradical shows a strong spin exchange interaction between both radicals which is modulated by temperature, but also gold nanoparticles (AuNPs) functionalized with this diradical permit investigation of such a phenomenon in surface-grafted radicals. The spin-labelled AuNP synthesis was optimized to obtain high coverage of spin labels to lead to high spin exchange interaction. The obtained AuNPs were studied by Electron Paramagnetic Resonance (EPR), UV-Vis, and IR spectroscopies, HR-TEM microscopy, Cyclic Voltammetry (CV), Energy Dispersive X-ray analysis (EDX) and Thermogravimetric Analysis (TGA). This inorganic-organic hybrid material also showed dipolar interactions between its radicals which were confirmed by the appearance in the EPR spectra of an |Deltams| = 2 transition at half-field. This signal gives direct evidence of the presence of a high-spin state and permitted us to study the nature of the magnetic coupling between the spins which was found to be antiferromagnetic. Self-Assembled Monolayers (SAMs) of these radicals on the Au (111) substrate were also prepared and studied by contact angle, X-Ray Photoelectron Spectroscopy (XPS), Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), Cyclic Voltammetry and EPR. The magnetic as well as the electrochemical properties of the hybrid surfaces were studied and compared with the properties of this diradical in solution. Analogies between the properties of AuNPs with high coverage of radicals and those of SAM were observed. PMID- 26864078 TI - The expanding role of metformin in cancer: an update on antitumor mechanisms and clinical development. AB - Metformin has been used for nearly a century to treat type 2 diabetes mellitus. Epidemiologic studies first identified the association between metformin and reduced risk of several cancers. The anticancer mechanisms of metformin involve both indirect or insulin-dependent pathways and direct or insulin-independent pathways. Preclinical studies have demonstrated metformin's broad anticancer activity across a spectrum of malignancies. Prospective clinical trials involving metformin in the chemoprevention and treatment of cancer now number in the hundreds. We provide an update on the anticancer mechanisms of metformin and review the results thus far available from prospective clinical trials investigating metformin's efficacy in cancer. PMID- 26864081 TI - Structural analysis of HyFlex EDM instruments. AB - AIM: To compare the phase transformation behaviour, the microstructure, the nano hardness and the surface chemistry of electro-discharge machined HyFlex EDM instruments with conventionally manufactured HyFlex CM. METHODOLOGY: New and laboratory used HyFlex EDM were examined by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Nano-hardness and modulus of elasticity were also investigated using a maximum load of 20 mN with a minimum of 40 significant indentations for each sample. Raman spectroscopy and field emission scanning electron microscope (FE-SEM) were used to assess the surface chemistry of HyFlex EDM. HyFlex CM were subjected to the same investigations and used as a comparison. Nano-indentation data were statistically analysed using the Student's t-test. RESULTS: XRD analysis on HyFlex EDM revealed the presence of martensite and rhombohedral R-phase, while a mixture of martensite and austenite structure was identified in HyFlex CM. DSC analysis also disclosed higher austenite finish (Af) temperatures for electro-discharge machining (EDM) instruments. Significant differences in nano-hardness and modulus of elasticity were found between EDM and CM files (P < 0.05). FE-SEM and EDS analyses confirmed that both new EDM and CM files were covered by an oxide layer. Micro-Raman spectroscopy assessed the presence of rutile-TiO2 . CONCLUSIONS: HyFlex EDM revealed peculiar structural properties, such as increased phase transformation temperatures and hardness. Present results corroborated previous findings and shed light on the enhanced mechanical behaviour of these instruments. PMID- 26864082 TI - A scalable synthesis of N-doped Si nanoparticles for high-performance Li-ion batteries. AB - N-doped Si nanoparticles were prepared synchronously by nitridation of Mg2Si. The existence of nitrogen doping can be demonstrated by the XPS spectrum and EELS energy-filtered images. When the N-doped Si nanoparticles were used as an anode for Li-ion batteries, a high reversible capacity of 2595 mA h g(-1) at 0.36 A g( 1) after 40 cycles, and 805 mA h g(-1) at 3.6 A g(-1) after 800 cycles could be obtained. PMID- 26864083 TI - Pneumatically actuated microvalve circuits for programmable automation of chemical and biochemical analysis. AB - Programmable microfluidic platforms (PMPs) are enabling significant advances in the utility of microfluidics for chemical and biochemical analysis. Traditional microfluidic devices are analogous to application-specific devices--a new device is needed to implement each new chemical or biochemical assay. PMPs are analogous to digital electronic processors--all that is needed to implement a new assay is a change in the order of operations conducted by the device. In this review, we introduce PMPs based on normally-closed microvalves. We discuss recent applications of PMPs in diverse fields including genetic analysis, antibody-based biomarker analysis, and chemical analysis in planetary exploration. Prospects, challenges, and future concepts for this emerging technology will also be presented. PMID- 26864084 TI - An Ultra-wideband and Polarization-independent Metasurface for RCS Reduction. AB - In this paper, an ultra-wideband and polarization-independent metasurface for radar cross section (RCS) reduction is proposed. The unit cell of the metasurface operates in a linear cross-polarization scheme in a broad band. The phase and amplitude of cross-polarized reflection can be separately controlled by its geometry and rotation angle. Based on the diffuse reflection theory, a 3-bit coding metasurface is designed to reduce the RCS in an ultra-wide band. The wideband property of the metasurface benefits from the wideband cross polarization conversion and flexible phase modulation. In addition, the polarization-independent feature of the metasurface is achieved by tailoring the rotation angle of each element. Both the simulated and measured results demonstrate that the proposed metasurface can reduce the RCS significantly in an ultra-wide frequency band for both normal and oblique incidences, which makes it promising in the applications such as electromagnetic cloaking. PMID- 26864085 TI - The ALSFRS as an outcome measure in therapeutic trials and its relationship to symptom onset. AB - The reduction in ALS Functional Rating Score (ALSFRS) from reported symptom onset to diagnosis is used to estimate rate of disease progression. ALSFRS decline may be non-linear or distorted by drop-outs in therapeutic trials, reducing the reliability of change in slope as an outcome measure. The PRO-ACT database uniquely allows such measures to be explored using historical data from negative therapeutic trials. The decline of functional scores was analysed in 18 pooled trials, comparing rates of decline based on symptom onset with rates calculated between interval assessments. Strategies to mitigate the effects of trial drop out were considered. Results showed that progression rate calculated by symptom onset underestimated the subsequent rate of disability accumulation, although it predicted survival more accurately than four-month interval estimates of deltaALSFRS or deltaFVC. Individual ALSFRS and FVC progression within a typical trial duration were linear. No simple solution to correct for trial drop-out was identified, but imputation using deltaALSFRS appeared least disruptive. In conclusion, there is a trade-off between the drive to recruit trial participants soon after symptom onset, and reduced reliability of the ALSFRS-derived progression rate at enrolment. The need for objective markers of disease activity as an alternative to survival-based end-points is clear and pressing. PMID- 26864086 TI - A dilation-driven vortex flow in sheared granular materials explains a rheometric anomaly. AB - Granular flows occur widely in nature and industry, yet a continuum description that captures their important features is yet not at hand. Recent experiments on granular materials sheared in a cylindrical Couette device revealed a puzzling anomaly, wherein all components of the stress rise nearly exponentially with depth. Here we show, using particle dynamics simulations and imaging experiments, that the stress anomaly arises from a remarkable vortex flow. For the entire range of fill heights explored, we observe a single toroidal vortex that spans the entire Couette cell and whose sense is opposite to the uppermost Taylor vortex in a fluid. We show that the vortex is driven by a combination of shear induced dilation, a phenomenon that has no analogue in fluids, and gravity flow. Dilatancy is an important feature of granular mechanics, but not adequately incorporated in existing models. PMID- 26864087 TI - Quantitatively resolving multivalent interactions on a macroscopic scale using force spectroscopy. AB - Multivalent interactions remain difficult to be characterized and consequently controlled, particularly on a macroscopic scale. Using force-induced remnant magnetization spectroscopy (FIRMS), we have resolved the single-, double-, and triple-biotin-streptavidin interactions, multivalent DNA interactions and CXCL12 CXCR4 interactions on millimetre-scale surfaces. Our results establish FIRMS as a viable method for systematic resolution and controlled formation of multivalent interactions. PMID- 26864088 TI - On the assessment of spatial resolution of PET systems with iterative image reconstruction. AB - Spatial resolution is an important metric for performance characterization in PET systems. Measuring spatial resolution is straightforward with a linear reconstruction algorithm, such as filtered backprojection, and can be performed by reconstructing a point source scan and calculating the full-width-at-half maximum (FWHM) along the principal directions. With the widespread adoption of iterative reconstruction methods, it is desirable to quantify the spatial resolution using an iterative reconstruction algorithm. However, the task can be difficult because the reconstruction algorithms are nonlinear and the non negativity constraint can artificially enhance the apparent spatial resolution if a point source image is reconstructed without any background. Thus, it was recommended that a background should be added to the point source data before reconstruction for resolution measurement. However, there has been no detailed study on the effect of the point source contrast on the measured spatial resolution. Here we use point source scans from a preclinical PET scanner to investigate the relationship between measured spatial resolution and the point source contrast. We also evaluate whether the reconstruction of an isolated point source is predictive of the ability of the system to resolve two adjacent point sources. Our results indicate that when the point source contrast is below a certain threshold, the measured FWHM remains stable. Once the contrast is above the threshold, the measured FWHM monotonically decreases with increasing point source contrast. In addition, the measured FWHM also monotonically decreases with iteration number for maximum likelihood estimate. Therefore, when measuring system resolution with an iterative reconstruction algorithm, we recommend using a low-contrast point source and a fixed number of iterations. PMID- 26864089 TI - Identification and Functional Prediction of Large Intergenic Noncoding RNAs (lincRNAs) in Rainbow Trout (Oncorhynchus mykiss). AB - Long noncoding RNAs (lncRNAs) have been recognized in recent years as key regulators of diverse cellular processes. Genome-wide large-scale projects have uncovered thousands of lncRNAs in many model organisms. Large intergenic noncoding RNAs (lincRNAs) are lncRNAs that are transcribed from intergenic regions of genomes. To date, no lincRNAs in non-model teleost fish have been reported. In this report, we present the first reference catalog of 9674 rainbow trout lincRNAs based on analysis of RNA-Seq data from 15 tissues. Systematic analysis revealed that lincRNAs in rainbow trout share many characteristics with those in other mammalian species. They are shorter and lower in exon number and expression level compared with protein-coding genes. They show tissue-specific expression pattern and are typically co-expressed with their neighboring genes. Co-expression network analysis suggested that many lincRNAs are associated with immune response, muscle differentiation, and neural development. The study provides an opportunity for future experimental and computational studies to uncover the functions of lincRNAs in rainbow trout. PMID- 26864090 TI - Specificity vs versatility: A fine balance for novel targeted molecular imaging radiotracers. PMID- 26864091 TI - Caffeine does not significantly reduce the sensitivity of vasodilator stress MPI: Rebuttal. PMID- 26864092 TI - Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy: 20-Year Follow-Up of West of Scotland Coronary Prevention Study. AB - BACKGROUND: Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. METHODS AND RESULTS: The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80 0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. CONCLUSION: Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. PMID- 26864093 TI - Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease. AB - BACKGROUND: Plastic bronchitis is a potentially fatal disorder occurring in children with single-ventricle physiology, and other diseases, as well, such as asthma. In this study, we report findings of abnormal pulmonary lymphatic flow, demonstrated by MRI lymphatic imaging, in patients with plastic bronchitis and percutaneous lymphatic intervention as a treatment for these patients. METHODS AND RESULTS: This is a retrospective case series of 18 patients with surgically corrected congenital heart disease and plastic bronchitis who presented for lymphatic imaging and intervention. Lymphatic imaging included heavy T2-weighted MRI and dynamic contrast-enhanced magnetic resonance lymphangiogram. All patients underwent bilateral intranodal lymphangiogram, and most patients underwent percutaneous lymphatic intervention. In 16 of 18 patients, MRI or lymphangiogram or both demonstrated retrograde lymphatic flow from the thoracic duct toward lung parenchyma. Intranodal lymphangiogram and thoracic duct catheterization was successful in all patients. Seventeen of 18 patients underwent either lymphatic embolization procedures or thoracic duct stenting with covered stents to exclude retrograde flow into the lungs. One of the 2 patients who did not have retrograde lymphatic flow did not undergo a lymphatic interventional procedure. A total of 15 of 17(88%) patients who underwent an intervention had significant symptomatic improvement at a median follow-up of 315 days (range, 45-770 days). The most common complication observed was nonspecific transient abdominal pain and transient hypotension. CONCLUSIONS: In this study, we demonstrated abnormal pulmonary lymphatic perfusion in most patients with plastic bronchitis. Interruption of the lymphatic flow resulted in significant improvement of symptoms in these patients and, in some cases, at least temporary resolution of cast formation. PMID- 26864094 TI - Hierarchical emergence of sequence sensitivity in the songbird auditory forebrain. AB - Bengalese finches (Lonchura striata var. domestica) generate more complex sequences in their songs than zebra finches. Because of this, we chose this species to explore the signal processing of sound sequence in the primary auditory forebrain area, field L, and in a secondary area, the caudomedial nidopallium (NCM). We simultaneously recorded activity from multiple single units in urethane-anesthetized birds. We successfully replicated the results of a previous study in awake zebra finches examining stimulus-specific habituation of NCM neurons to conspecific songs. Then, we used an oddball paradigm and compared the neural response to deviant sounds that were presented infrequently, with the response to standard sounds, which were presented frequently. In a single sound oddball task, two different song elements were assigned for the deviant and standard sounds. The response bias to deviant elements was larger in NCM than in field L. In a triplet sequence oddball task, two triplet sequences containing elements ABC and ACB were assigned as the deviant and standard. Only neurons in NCM that displayed broad-shaped spike waveforms had sensitivity to the difference in element order. Our results suggest the hierarchical processing of complex sound sequences in the songbird auditory forebrain. PMID- 26864095 TI - Emollient efficacy and acceptability in the treatment of eczematous dry skin: A double-blind, randomised comparison of two UK-marketed products. AB - OBJECTIVE: The aim of this study was to compare the moisturising efficacy and acceptability of physical characteristics of two commonly prescribed emollients licenced in the UK, Doublebase Dayleve gel (DELP) and Diprobase cream (DIPC). METHODS: The study was a double-blind, concurrent bi-lateral comparison in female eczema subjects with dry skin. RESULTS: In Part 1, comparing the area under the curve (AUC) change from baseline corneometer readings over 24 h following single applications of the emollients to the volar forearms of 34 subjects, the AUC for DELP was more than three times that seen for DIPC (p < 0.0001). In Part 2, comparing the same outcome measured over 5 days of twice daily applications to the lower legs in 36 subjects, the AUC for DELP was approximately five times that for DIPC (p < 0.0001). 69% of subjects "Like Slightly" or "Like Strongly" DELP compared to 33% for DIPC (p = 0.025). 72% indicated they would use DELP again compared to 33% for DIPC (p = 0.033). 75% of subjects preferred DELP, 17% preferred DIPC and 8% expressed no preference (p = 0.0004). PMID- 26864097 TI - Notification that new names of prokaryotes, new combinations and new taxonomic opinions have appeared in volume 65, part 10, of the IJSEM. AB - This listing of names of prokaryotes published in a previous issue of the IJSEM is provided as a service to bacteriology to assist in the recognition of new names and new combinations. This procedure was proposed by the Judicial Commission [Minute 11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are listed according to the Rules of priority (i.e. page number and order of valid publication of names in the original articles).ijsem000745-t01. PMID- 26864096 TI - Takotsubo Cardiomyopathy: What we have Learned in the Last 25 Years? (A Comparative Literature Review). AB - We performed a comparative literature review, to elucidate the major features of the Takotsubo (stress) cardiomyopathy (TCM) collected in last 25 years. TCM is characterized by left- or biventricular apical ballooning with a clinical presentation, electrocardiographic abnormalities, and biomarker profils similar to those seen in acute myocardial infarction. Epidemiological studies have shown that TCM is more common in postmenopausal women; however exact figures are not available. The underlying aetiology is still largely undetermined. Elevated catecholamine levels, lack of estrogen, disturbed myocardial fatty acid metabolism and plaque rupture with spontaneous thrombolysis are potentially discussed mechanisms responsible for inducing a prolonged stunned myocardium. Strong emotional or physical stress is the most frequently described trigger in the literature. Therapy recommendations include appropriate antiplatelet treatment, beta-blockers and ACE inhibitors. The abnormal kinetics usually resolve or improve within a month and carry a favorable prognosis in most cases. However, all the suspected complications of an acute myocardial infarction, including cardiogenic shock or lethal arrhythmias, may still occur. PMID- 26864098 TI - The promotional effect of surface defects on the catalytic performance of supported nickel-based catalysts. AB - Controlling the metal-support interactions, as well as the nature of support materials, is of vital importance for enhancing the catalytic performance of supported metal catalysts. In the present work, supported nickel nanocatalysts with abundant surface defects (e.g. oxygen vacancies, Ti(3+) species) were directly synthesized via a facile single-source Ni-Ti layered double hydroxide precursor route, and their catalytic performance in the liquid phase selective hydrogenation of chloronitrobenzenes to chloroanilines was investigated. A series of characterization techniques including XRD, TEM, STEM, PL, XPS, H2-TPR and H2 chemisorption clearly demonstrated that the resultant Ni nanoparticles were uniformly dispersed on the surface of the Ni-Ti mixed metal oxide support formed in situ, thereby leading to strong metal-support interactions and the formation of a large amount of surface oxygen vacancies and Ti(3+) species. Compared with that prepared using a conventional impregnation method, the as-formed Ni-based nanocatalysts exhibited significantly enhanced catalytic performance with a high chloroaniline yield of 99.0% under mild reaction conditions (i.e. a low hydrogen pressure of 0.2 MPa). Such an unprecedented catalytic efficiency was mainly attributed to the promotional effect of surface defects. Furthermore, the present Ni-based nanocatalysts could be reused five times without serious aggregation of active species and remarkable activity loss, indicative of high stability. PMID- 26864099 TI - Optical Dark Rogue Wave. AB - Photonics enables to develop simple lab experiments that mimic water rogue wave generation phenomena, as well as relativistic gravitational effects such as event horizons, gravitational lensing and Hawking radiation. The basis for analog gravity experiments is light propagation through an effective moving medium obtained via the nonlinear response of the material. So far, analogue gravity kinematics was reproduced in scalar optical wave propagation test models. Multimode and spatiotemporal nonlinear interactions exhibit a rich spectrum of excitations, which may substantially expand the range of rogue wave phenomena, and lead to novel space-time analogies, for example with multi-particle interactions. By injecting two colliding and modulated pumps with orthogonal states of polarization in a randomly birefringent telecommunication optical fiber, we provide the first experimental demonstration of an optical dark rogue wave. We also introduce the concept of multi-component analog gravity, whereby localized spatiotemporal horizons are associated with the dark rogue wave solution of the two-component nonlinear Schrodinger system. PMID- 26864100 TI - Antibodies as leading tools to unlock the therapeutic potential in human disease. PMID- 26864102 TI - Fostering of advanced mutualism with gut microbiota by Immunoglobulin A. AB - Immunoglobulin A (IgA), the most abundantly secreted antibody isotype in mammals, not only provides direct immune protection to neonates via maternal milk but also helps program the infant immune system by regulating the microbiota. IgA continues to maintain dynamic interactions with the gut microbiota throughout life and this influences immune system homeostasis as well as other physiological processes. The secretory IgA produced independently of T-cell selection are commonly referred to as natural or innate antibodies. Our studies have shown that innate-IgA, while effective at excluding microorganisms from the gut, does not promote mutualism with the microbiota in the same way as adaptive-IgA that is selected in T cell-dependent germinal center reactions. Adaptive-IgA fosters more advanced mutualism with the microbiota than innate-IgA by selecting and diversifying beneficial microbial communities. In this review, we suggest that the diversified microbiota resulting from adaptive-IgA pressure was pivotal in promoting ecological adaptability and speciation potential of mammals. PMID- 26864101 TI - Regulation of germinal center B-cell differentiation. AB - Germinal centers (GC) are the main sites where antigen-activated B-cell clones expand and undergo immunoglobulin gene hypermutation and selection. Iterations of this process will lead to affinity maturation, replicating Darwinian evolution on the cellular level. GC B-cell selection can lead to four different outcomes: further expansion and evolution, apoptosis (non-selection), or output from the GC with differentiation into memory B cells or plasma cells. T-helper cells in GC have been shown to have a central role in regulating B-cell selection by sensing the density of major histocompatibility complex (MHC):peptide antigen complexes. Antigen is provided on follicular dendritic cells in the form of immune complex. Antibody on these immune complexes regulates antigen accessibility by shielding antigen from B-cell receptor access. Replacement of antibody on immune complexes by antibody generated from GC-derived plasma cell output will gradually reduce the availability of antigen. This antibody feedback can lead to a situation where a slow rise in selection stringency caused by a changing environment leads to directional evolution toward higher affinity antibody. PMID- 26864104 TI - Discovery and bio-optimization of human antibody therapeutics using the XenoMouse(r) transgenic mouse platform. AB - Since the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform--the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer--was developed using XenoMouse((r)) technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse((r)) platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large-scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio-optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards. PMID- 26864103 TI - Manipulation of the glycan-specific natural antibody repertoire for immunotherapy. AB - Natural immunoglobulin derived from innate-like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan-specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate-like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan-reactive B cell pool. Glycan-reactive natural antibodies (NAbs) have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan-reactive NAb repertoire is therefore paramount. A more thorough understanding of NAb repertoire development holds promise for the design of both biological diagnostics and therapies. In this article, we review the development and functions of NAbs and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in NAb repertoire development. We also discuss the implications of increased clonal plasticity of the innate-like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system. PMID- 26864105 TI - Stable long-term cultures of self-renewing B cells and their applications. AB - Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen-presenting cells for the discovery of tumor neoantigens. PMID- 26864106 TI - Targeting plasma cells: are we any closer to a panacea for diseases of antibody secreting cells? AB - Antibody-secreting cells (ASCs) are critical for a functional and effective adaptive immune system. In a number of illnesses, however, these same cells contribute to the underlying disease state leading to significant morbidity and mortality. While therapeutic targeting of antibody-secreting cells has progressed significantly over the last two decades, many of these conditions remain major health problems. In this review, we will discuss current and potential therapeutic targeting of ASCs in the context of the known biology of these cells. PMID- 26864107 TI - Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. AB - CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti-tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38-targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody-mediated autoimmune diseases. PMID- 26864109 TI - Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation. AB - Monoclonal antibodies have become a general modality in therapeutic development, and a variety of monoclonal antibodies targeting soluble antigens have been developed. However, even with infinite binding affinity to an antigen, a conventional antibody can bind to the antigen only once and results in an increase in total plasma antigen concentration in vivo. This antibody-mediated antigen accumulation generally occurs because the clearance from circulation of an antibody-antigen complex is much slower than that of a free antigen. This limitation has recently been overcome by sweeping antibodies, which are capable of actively eliminating soluble antigens from circulation. A sweeping antibody incorporates two antibody engineering technologies: one is variable region engineering to enable the antibody to bind to an antigen in plasma and dissociate from the antigen in endosome (after which the antigen undergoes lysosomal degradation), and the other is constant region engineering to increase the cellular uptake of the antibody-antigen complex into endosome. By enhancing the elimination of soluble antigens from circulation, sweeping antibodies can therapeutically target soluble antigens that conventional antibodies cannot. This review discusses the features, engineering technologies, advantages, and applications of sweeping antibodies that target soluble antigens. PMID- 26864108 TI - Engineered IgG1-Fc--one fragment to bind them all. AB - The crystallizable fragment (Fc) of the immunoglobulin class G (IgG) is a very attractive scaffold for the design of novel therapeutics due to its quality of uniting all essential antibody functions. This article reviews the functionalization of this homodimeric glycoprotein by diversification of structural loops of CH3 domains for the design of Fcabs, i.e. antigen-binding Fc proteins. It reports the design of libraries for the selection of nanomolar binders with wildtype-like in vivo half-life and correlation of Fc receptor binding and ADCC. The in vitro and preclinical biological activity of selected Fcabs is compared with that of clinically approved antibodies. Recently, the great potential of the scaffold for the development of therapeutics for clinical use has been shown when the HER2-binding Fcab FS102 entered clinical phase I. Furthermore, methods for the engineering of biophysical properties of Fcabs applicable to proteins in general are presented as well as the different approaches in the design of heterodimeric Fc-based scaffolds used in the generation of bispecific monoclonal antibodies. Finally, this work critically analyzes and compares the various efforts in the design of highly diverse and functional libraries that have been made in the engineering of IgG1-Fc and structurally similar scaffolds. PMID- 26864110 TI - Immunogenicity of therapeutic recombinant immunotoxins. AB - Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38-kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less-immunogenic RITs by identifying and removing T- and B-cell epitopes to hide the RIT from the immune system. PMID- 26864111 TI - Engineered hapten-binding antibody derivatives for modulation of pharmacokinetic properties of small molecules and targeted payload delivery. AB - Hapten-binding antibodies have for more than 50 years played a pivotal role in immunology, paving the way to antibody generation (as haptens are very important and robust immunogens), to antibody characterization (as the first structures generated more than 40 years ago were those of hapten binders), and enabled and expanded antibody engineering technologies. The latter field of engineered antibodies evolved over many years and many steps resulting in recombinant humanized or human-derived antibody derivatives in multiple formats. Today, hapten-binding antibodies are applied not only as reagents and tools (where they still play an important part) but evolved also to engineered targeting and pretargeting vehicles for disease diagnosis and therapy. Here we describe recent applications of hapten-binding antibodies and of engineered mono- and bispecific hapten-binding antibody derivatives. We have designed and applied these molecules for the modulation of the pharmacokinetic properties of small compounds or peptides. They are also integrated as additional binding entities into bispecific antibody formats. Here they serve as non-covalent or covalent coupling modules to haptenylated compounds, to enable targeted payload delivery to disease tissues or cells. PMID- 26864112 TI - Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site. AB - The activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance in vivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents. PMID- 26864113 TI - Harnessing T cells to fight cancer with BiTE(r) antibody constructs--past developments and future directions. AB - Bispecific T-cell engager (BiTE((r))) antibody constructs represent a novel immunotherapy that bridges cytotoxic T cells to tumor cells, thereby inducing target cell-dependent polyclonal T-cell activation and proliferation, and leading to apoptosis of bound tumor cells. Anti-CD19 BiTE((r)) blinatumomab has demonstrated clinical activity in Philadelphia chromosome (Ph)-negative relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) eventually resulting in conditional approval by the U.S. Food and Drug Administration in 2014. This drug is currently further developed in pediatric and Ph(+) r/r, as well as in minimal residual disease-positive ALL, and might also offer clinical benefit for patients with non-Hodgkin's lymphoma, especially for those with aggressive forms like diffuse large B-cell lymphoma. Another BiTE((r)) antibody construct in hemato oncology designated AMG 330 targets CD33 on acute myeloid leukemia blast cells. After showing promising ex vivo activity, this drug candidate has recently entered phase 1 clinical development, and has further indicated potential for combination with checkpoint inhibitors. In solid tumor indications, three BiTE((r)) antibody constructs have been tested in phase 1 studies so far: anti EpCAM BiTE((r)) AMG 110, anti-CEA BiTE((r)) MEDI-565/AMG 211, and anti-PSMA BiTE((r)) BAY2010112/AMG 212. Pertinent questions comprise how to maximize BiTE((r)) penetration and T-cell infiltration of the tumor while simultaneously minimizing any adverse events, which is currently explored by a continuous intravenous infusion approach. Thus, BiTE((r)) antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need. PMID- 26864114 TI - Developing genetic tools to exploit Chaetomium thermophilum for biochemical analyses of eukaryotic macromolecular assemblies. AB - We describe a method to genetically manipulate Chaetomium thermophilum, a eukaryotic thermophile, along with various biochemical applications. The transformation method depends on a thermostable endogenous selection marker operating at high temperatures combined with chromosomal integration of target genes. Our technique allows exploiting eukaryotic thermophiles as source for purifying thermostable native macromolecular complexes with an emphasis on the nuclear pore complex, holding great potential for applications in basic science and biotechnology. PMID- 26864115 TI - Sexual and reproductive health of young people with disability in Ethiopia: a study on knowledge, attitude and practice: a cross-sectional study. AB - BACKGROUND: As is common in developing countries, in Ethiopia young people with disabilities (YPWD) are more likely than the general population to be illiterate, unemployed and impoverished. They often lack equal access to information and education for reasons ranging from barriers regarding physical access to services to varied special learning needs. Very little is known about knowledge, attitude and practice (KAP) of YPWD regarding sexual and reproductive health (SRH) related issues. We, therefore, aimed to assess the KAP of 426 YPWD in Addis Ababa, Ethiopia. METHODS: A cross-sectional survey was conducted in 2012. Data were collected by trained interviewers using a structured questionnaire covering socio demographic information, as well as information on KAP regarding SRH. RESULTS: Only 64.6% of YPWD were aware of SRH services. Radio and TV were mentioned as the main sources of information by 62.2% of the participants. 77.9% had never had a discussion about SRH topics with their parents. Even though 96.7% of the respondents had heard about HIV, 88% had poor knowledge about ways of preventing HIV. Perception of the risk of getting infected with HIV was found to be generally low in YPWD; only 21.6% believed that they were at risk of acquiring HIV. CONCLUSIONS: Our study, in general, demonstrated that there is a lack of comprehensive knowledge, appropriate practice and favorable attitude of YPWD regarding different SRH-related issues. Our findings thus clearly indicate the need for strategies and programs to raise SRH-related awareness and to help YPWD to develop the appropriate skills and attitudes needed for a healthy reproductive life. PMID- 26864117 TI - Population and phylogenomic decomposition via genotyping-by-sequencing in Australian Pelargonium. AB - Species delimitation has seen a paradigm shift as increasing accessibility of genomic-scale data enables separation of lineages with convergent morphological traits and the merging of recently diverged ecotypes that have distinguishing characteristics. We inferred the process of lineage formation among Australian species in the widespread and highly variable genus Pelargonium by combining phylogenomic and population genomic analyses along with breeding system studies and character analysis. Phylogenomic analysis and population genetic clustering supported seven of the eight currently described species but provided little evidence for differences in genetic structure within the most widely distributed group that containing P. australe. In contrast, morphometric analysis detected three deep lineages within Australian Pelargonium; with P. australe consisting of five previously unrecognized entities occupying separate geographic ranges. The genomic approach enabled elucidation of parallel evolution in some traits formerly used to delineate species, as well as identification of ecotypic morphological differentiation within recognized species. Highly variable morphology and trait convergence each contribute to the discordance between phylogenomic relationships and morphological taxonomy. Data suggest that genetic divergence among species within the Australian Pelargonium may result from allopatric speciation while morphological differentiation within and among species may be more strongly driven by environmental differences. PMID- 26864116 TI - Illuminating necrosis: From mechanistic exploration to preclinical application using fluorescence molecular imaging with indocyanine green. AB - Tissue necrosis commonly accompanies the development of a wide range of serious diseases. Therefore, highly sensitive detection and precise boundary delineation of necrotic tissue via effective imaging techniques are crucial for clinical treatments; however, no imaging modalities have achieved satisfactory results to date. Although fluorescence molecular imaging (FMI) shows potential in this regard, no effective necrosis-avid fluorescent probe has been developed for clinical applications. Here, we demonstrate that indocyanine green (ICG) can achieve high avidity of necrotic tissue owing to its interaction with lipoprotein (LP) and phospholipids. The mechanism was explored at the cellular and molecular levels through a series of in vitro studies. Detection of necrotic tissue and real-time image-guided surgery were successfully achieved in different organs of different animal models with the help of FMI using in house-designed imaging devices. The results indicated that necrotic tissue with a 0.6 mm diameter could be effectively detected with precise boundary definition. We believe that the new discovery and the associated imaging techniques will improve personalized and precise surgery in the near future. PMID- 26864120 TI - Triggering Gel Formation and Luminescence through Donor-Acceptor Interactions in a C3 -Symmetric Tris(pyrene) System. AB - Straightforward modulation of the gelation, absorption and luminescent properties of a tris(pyrene) organogelator containing a C3 -symmetric benzene-1,3,5 tricarboxamide central unit functionalized by three 3,3'-diamino-2,2'-bipyridine fragments is achieved through donor-acceptor interactions in the presence of tetracyanoquinodimethane. PMID- 26864118 TI - Patient satisfaction with a teleradiology service in general practice. AB - BACKGROUND: Accessibility to secondary health services is not always easy for patients who live at a great distance of hospital. In these circumstances, transferring diagnostic tools and treatment options to primary care could prove beneficial for patients. To do so, the quality of medical care and the costs and benefits of the approach need to be assessed. However, the patient perspective is equally important, offering important insights. METHODS: In a cross-sectional study we investigate the satisfaction of patients toward a new teleradiology facility offered a general practice on Ameland, an island in the Netherlands. A questionnaire was created based on the Dutch version of the Patient Satisfaction Questionnaire III and completed by all patients after receiving an x-ray in primary care between June 1, 2007 and June 1, 2009. Those who received more than one x-ray in that period were included only once. The technical and interpersonal skills of doctors were rated out the sum score of the questionnaire namely 25 and 30, respectively. Analysis of variance (ANOVA) was used to analyze the differences between the means of the satisfaction subscales and the patient characteristics. RESULTS: The response proportion was after reminder 65% (381/587 patients). Satisfaction with the technical skills of the doctor providing the teleradiology service was 22.4 +/- 3.7, while satisfaction with the interpersonal skills of the doctor during the diagnostic phase was 26.8 +/- 3.8. Island residents, the elderly, and those with no history of trauma were more satisfied with the technical and interpersonal aspects of the consultation than non residents, younger patients, and those with a history of trauma. CONCLUSION: Patients in the island community of Ameland experienced high levels of satisfaction with the teleradiology service offered in primary care. PMID- 26864121 TI - Potential role of systemic thrombolysis in acute submassive intermediate risk pulmonary embolism: review and future perspectives. AB - Submassive (intermediate risk) pulmonary embolism (PE) continues to be a significantly morbid disease process that remains unrecognized, inadequately risk stratified and suboptimally treated. Appropriate early clinical and imaging-based risk stratification represents the cornerstone for adequate therapeutic decision making, particularly for the selection of candidates who may benefit the most from systemic thrombolysis. The relevance of estimating clinical prognostic scores, in combination with imaging data, for accurate assessment of right ventricular function and laboratory biomarkers, indicative of myocardial injury for identification of normotensive patients at intermediate risk for an adverse short-term outcome are emphasized in this review. Recent clinical trials have demonstrated improvement in hemodynamics and mortality with the use of systemic thrombolysis among intermediate risk patients; however, it came at the cost of a significantly increased risk of major bleeding. Catheter-based therapies have garnered considerable clinical interest in recent years; of particular note is the ultrasound accelerated catheter-directed thrombolysis which has emerged as a novel and attractive alternative therapeutic modality with an increasing number of single center studies and ongoing randomized trials. Our review focuses on the major trials and studies involved in submassive PE in the recent literature including the role of thrombolytic therapy. We include major trials with reasonable sample size and extensive review of the potential side effects, such as major bleeding. PMID- 26864122 TI - Alkaline-Earth-Catalysed Cross-Dehydrocoupling of Amines and Hydrosilanes: Reactivity Trends, Scope and Mechanism. AB - Alkaline-earth (Ae=Ca, Sr, Ba) complexes are shown to catalyse the chemoselective cross-dehydrocoupling (CDC) of amines and hydrosilanes. Key trends were delineated in the benchmark couplings of Ph3 SiH with pyrrolidine or tBuNH2 . Ae{E(SiMe3)2}2 ?(THF)x (E=N, CH; x=2-3) are more efficient than {N^N}Ae{E(SiMe3)2}?(THF)n (E=N, CH; n=1-2) complexes (where {N^N}(-) ={ArN(o C6H4)C(H)=NAr}(-) with Ar=2,6-iPr2 -C6H3) bearing an iminoanilide ligand, and alkyl precatalysts are better than amido analogues. Turnover frequencies (TOFs) increase in the order Ca30 products) includes diamines and di(hydrosilane)s. Kinetic analysis of the Ba-promoted CDC of pyrrolidine and Ph3SiH shows that 1) the kinetic law is rate=k[Ba](1) [amine](0) [hydrosilane](1), 2) electron-withdrawing p-substituents on the arylhydrosilane improve the reaction rate and 3) a maximal kinetic isotopic effect (kSiH/kSiD =4.7) is seen for Ph3SiX (X=H, D). DFT calculations identified the prevailing mechanism; instead of an inaccessible sigma-bond-breaking metathesis pathway, the CDC appears to follow a stepwise reaction path with N-Si bond-forming nucleophilic attack of the catalytically competent Ba pyrrolide onto the incoming silane, followed by rate limiting hydrogen-atom transfer to barium. The participation of a Ba silyl species is prevented energetically. The reactivity trend Ca=50 years with prior CV disease; (2) aged >=60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 +/- 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints. PMID- 26864125 TI - An online tool for obesity intervention and public health. AB - BACKGROUND: Though the United States of America (U.S.A.) obesity rate shows signs of leveling off, rates remain high. Poor nutrition contributes to the development of obesity, and physical inactivity is an important cause of numerous diseases and directly linked to obesity. Efforts to improve diet, increase physical activity and pursue other behavioral changes seem imperative. However, the effective management of intervention strategies for large number of participants are challenging because services in primary, secondary, and tertiary cares are often under-resourced, relatively uncoordinated with other parts of the health system. It is thus necessary to have accompanying intervention strategies that can be carried out at population level. In this paper, we describe an online intervention tool designed for the Obesity Prevention Tailored for Health II project to help achieve such goals. RESULTS: The first part of the online tool locates healthy food stores and recreational programs within a specified distance of a participant's home or a place of interest. The food environments include fruit & vegetable stores, farmers' markets and grocery stores, and the companying popup window shows the street address and contact information of each store. The parks and recreational programs are displayed on names of park or recreational program, types of program available, and city each amenity belongs to. The tool also provides spatial coverage of vegetation greenness, air pollution and of historical traffic accidents involving active travel. The second part of the tool provides optimized travel options for reaching various amenities. By incorporating bicycling, walking and public transit into the trip planner, this online tool helps increase active transport and reduce dependence on automobiles. It promotes transportation that encourages safety awareness, physical activity, health, recreation, and resource conservation. CONCLUSIONS: We developed the first Google-based online intervention tool that assists obese and overweight participants in finding food and recreational amenities around locations of interest and identifying optimized routes that fit their personal preferences. This tool can also serve general public and policy makers for education, disease prevention and health promotion. PMID- 26864126 TI - Tempest in a teapot: A systematic review of HPV vaccination and risk compensation research. AB - There has been some concern among parents and in the media that vaccinating children against human papillomavirus could be seen as giving children permission to engage in risky sexual behaviors (also known as sexual disinhibition). Several studies have found this concern to be unfounded but there have been no attempts to synthesize the relevant studies in order to assess if there is evidence of sexual disinhibition. The aim of this study was to synthesize recent literature examining sexual behaviors and biological outcomes (e.g., sexually transmitted infections) post-HPV vaccination. We reviewed literature from January 1, 2008 June 30, 2015 using PubMed, CINAHL, and Embase with the following search terms: [(sex behavior OR sex behavior OR sexual) AND (human papillomavirus OR HPV) AND (vaccines OR vaccine OR vaccination)] followed by a cited reference search. We included studies that examined biological outcomes and reported behaviors post vaccination in both males and females. Studies were reviewed by title and abstract and relevant studies were examined as full-text articles. We identified 2,503 articles and 20 were eventually included in the review. None of the studies of sexual behaviors and/or biological outcomes found evidence of riskier behaviors or higher rates of STIs after HPV vaccination. Instead, the studies found that vaccinated compared to unvaccinated individuals were less likely to report vaginal intercourse without a condom (OR = 0.5; 95%CI = 0.4-0.6) and non use of contraception (OR = 0.27; 95%CI = 0.15-0.48) and unvaccinated participants had higher rates of Chlamydia (OR = 2.3; 95%CI = 1.06-5.00). These results should be reassuring to parents and health care providers. PMID- 26864127 TI - Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women. AB - There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year old women (n 33) in Helsinki (60 degrees N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 ug D2 or D3/d; D2 supplement and regular bread=25 ug D2/d; D3 supplement and regular bread=25 ug D3/d; and placebo pill and D2-biofortified bread=25 ug D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S 25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65.1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0.707) or S 25(OH)D3 (P=0.490), but increased S-25(OH)D2 compared with placebo (P<0.001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0.001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0.030 and P=0.001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0.001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool. PMID- 26864128 TI - Experimental models for contamination of titanium surfaces and disinfection protocols. AB - AIM: The aim of this pilot study was to describe an in vitro model of peri implantitis microcosm for contamination of titanium surfaces and an in vivo model for evaluating different disinfection strategies of titanium surfaces. MATERIALS AND METHODS: Biofilms were grown in vitro for 30 days on sandblasted large-grit acid-etched (SLA) Ti discs (n = 69) in a constant depth film fermentor (CDFF) associated with peri-implantitis conditions. Four Swedish loop rabbits were randomly allocated in three test groups (T1 , T2 , T3 ) and one control group (C). In group C, two sterile SLA Ti discs were implanted/fixed in each tibia. In the test groups (to evaluate the potential of different surface disinfection techniques), one sterile and three previously disinfected SLA Ti discs were placed following different disinfection protocols: group T1 : the discs were treated with a titanium brush - TiB; group T2 : the discs were treated with the combination of TiB and photodynamic therapy; and group T3 : the discs were treated with TiB and 1%NaOCl plus 0.2%CHX. Tensile strength test and qualitative histological analysis were performed on all 16 discs after 4 weeks of healing. RESULTS: Thirty days following CDFF emulating peri-implantitis microcosm, all SLA Ti discs had a mean total viable aerobes and facultative anaerobes count of 8.06 log10 CFU/biofilm and anaerobes 8.32 log10 CFU/biofilm. Before implantation/fixation on the tibia, differences of log10 CFU/biofilm counts between control and test groups after post hoc adjustment were highly significant (P < 0.001). In the in vivo analysis, group C exhibited the highest tensile strength (67.60 N [25.64-127.02]) and the histological sections revealed the presence of dense mature bone in direct contact with the disc surface. The analysis at the test groups showed that T2 presented with the highest tensile strength in comparison with the other two test groups. CONCLUSIONS: The in vitro model used in this study provides a valuable and reproducible tool for evaluating the in vitro dynamics of the peri-implantitis microcosm biofilm and for contaminating in a reproducible manner titanium surfaces. At the same time, the in vivo model used in this study provides a standardised mode of evaluating disinfection modalities of previously infected titanium surfaces. PMID- 26864129 TI - In vivo monitoring of local pH values in a live rat brain based on the design of a specific electroactive molecule for H(+). AB - pH plays an important role in the biochemical, ion-regulatory, or electrical machinery of nerve and glial cells, and is considered to be related to a number of degenerative diseases. Herein, we first develop a two-channel electrochemical ratiometric biosensor for local pH determination in a live rat brain, and report the accurate pH values in the different regions of live brains upon global cerebral ischemia. PMID- 26864130 TI - DNACPR: Venn's perverse view. PMID- 26864131 TI - A randomized, double-blind, placebo-controlled, Phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. AB - OBJECTIVE: This analysis of the Japanese subpopulation of the PALETTE Phase III, randomized, placebo-controlled study investigated efficacy and safety of pazopanib in patients with metastatic soft tissue sarcoma after failure of standard chemotherapy. METHODS: Patients were randomly assigned in a 2:1 ratio to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross over. Primary endpoint was progression-free survival. Secondary endpoints included overall survival and overall response rate. Efficacy analysis was by intent-to-treat. Safety was also investigated. RESULTS: Forty-seven patients received either pazopanib (n = 31) or placebo (n = 16). Median progression-free survival was 7.0 weeks (95% confidence interval: 4.0-11.7) for placebo and 24.7 weeks (95% confidence interval: 8.6-28.1) for pazopanib (hazard ratio = 0.41 [95% confidence interval: 0.19-0.90]; P = 0.002). Median overall survival was 14.9 months (95% confidence interval: 6.8-not calculable) for placebo and 15.4 months (95% confidence interval: 7.9-28.8) for pazopanib (hazard ratio = 0.87 [95% confidence interval: 0.41-1.83]; P = 0.687). More patients receiving pazopanib experienced best response of stable disease versus placebo. Adverse events were similar to the global population; those leading to dose reduction were more common and mean daily dose was lower in the Japanese population versus the global population (45 vs. 32% and 624.4 vs. 700.4 mg, respectively). CONCLUSIONS: The efficacy and safety of pazopanib observed in the Japanese subpopulation of PALETTE were similar to those in the global population. Pazopanib is a new treatment option for Japanese patients with metastatic non-adipocytic soft tissue sarcoma after chemotherapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT00753688; GSK study ID: VEG110727; http://www.gsk-clinicalstudyregister.com/study/VEG110727#ps. PMID- 26864132 TI - Repeat biopsy of primary disease negatively affects the outcome of patients with nasopharyngeal cancer treated with definitive intensity-modified radiotherapy: a cohort analysis of 795 patients. AB - OBJECTIVE: To determine whether pretreatment repeat biopsy of nasopharynx is associated with an impaired outcome in nasopharyngeal carcinoma patients in an intensity-modified radiotherapy era. METHODS: We performed a retrospective data review of the association between pretreatment nasopharyngeal biopsy and outcomes for all nasopharyngeal carcinoma patients treated at our center between January 2007 and December 2011. Of the 720 patients enrolled, 693 (96.3%) were diagnosed after initial biopsy and 27 (3.7%) after repeat biopsy. Five-year cancer-specific survival, disease-free survival and distant metastasis-free survival for the two groups were compared using univariate and multivariate analyses to evaluate the effects of repeat biopsy on the outcome. RESULTS: Five-year estimated cancer specific survival (75.9 vs. 88.5%, P= 0.045) and disease-free survival (63.3 vs. 77.1%, P= 0.041) were significantly poorer in the repeat biopsy group than the initial biopsy group. After adjustment for other prognostic factors (age, gender, T and N stage), pretreatment biopsy remained independently associated with poorer both 5-year cancer-specific survival and disease-free survival. The hazard ratios for cancer-specific survival and disease-free survival in the repeat biopsy group were 2.73 (95% confidence interval 1.09-6.82) and 2.22 (95% confidence interval 1.12-4.37) compared with the initial biopsy group (reference), respectively. The repeat biopsy group also had a higher risk of distant failure compared with the initial biopsy group (hazard ratio 2.82, 95% confidence interval 1.22-6.51, P= 0.015). CONCLUSION: Pretreatment repeat biopsy of nasopharynx has a detrimental effect on survivals of nasopharyngeal carcinoma patients, which may be partly due to an increased frequency of distant metastasis. PMID- 26864133 TI - Pediatric rheumatology consultant workforce in Australia and New Zealand: the current state of play and challenges for the future. AB - AIM: There have been no formal assessments of current levels of the pediatric rheumatology workforce in Australia and New Zealand. Despite this it is felt that we fall well behind international guidelines placing children and adolescents with rheumatic diseases at risk of suboptimal care. Overcoming this shortfall in specialist pediatric rheumatology care requires documentation and recognition of the shortfall and a commitment from the health system to support improvements to supplement the current specialist workforce. The purpose of this survey was to assess the current state of play of the pediatric rheumatology workforce in Australia and New Zealand. METHODS: The Australian Paediatric Rheumatology Group (APRG) conducted a survey, which examined the current pediatric rheumatology workforce in Australia and New Zealand. The survey was sent via email link to a survey hosted by ZoomerangTM to 49 physicians known to treat patients with pediatric rheumatic diseases and they were asked to forward the survey to any others who they knew saw children with rheumatic disease. RESULTS: Currently there is a shortfall in the pediatric rheumatology workforce of 68% based on minimum requirements and a shortfall of 225% based on an ideal scenario. CONCLUSION: Currently in Australia and New Zealand we fail to provide the level of care to children with pediatric rheumatic diseases comparable to other developed health economies worldwide. The current deficiency requires an increase in resource allocation to clinical service and speciality training to overcome this disparity and ensure children in Australia and New Zealand receive internationally recognized standards of care. PMID- 26864134 TI - Insights into the naturally acquired immune response to Plasmodium vivax malaria. AB - Plasmodium vivax is the most geographically widespread of the malaria parasites causing human disease, yet it is comparatively understudied compared with Plasmodium falciparum. In this article we review what is known about naturally acquired immunity to P. vivax, and importantly, how this differs to that acquired against P. falciparum. Immunity to clinical P. vivax infection is acquired more quickly than to P. falciparum, and evidence suggests humans in endemic areas also have a greater capacity to mount a successful immunological memory response to this pathogen. Both of these factors give promise to the idea of a successful P. vivax vaccine. We review what is known about both the cellular and humoral immune response, including the role of cytokines, antibodies, immunoregulation, immune memory and immune dysfunction. Furthermore, we discuss where the future lies in terms of advancing our understanding of naturally acquired immunity to P. vivax, through the use of well-designed longitudinal epidemiological studies and modern tools available to immunologists. PMID- 26864135 TI - Immune activation and induction of memory: lessons learned from controlled human malaria infection with Plasmodium falciparum. AB - Controlled human malaria infections (CHMIs) are a powerful tool to assess the efficacy of drugs and/or vaccine candidates, but also to study anti-malarial immune responses at well-defined time points after infection. In this review, we discuss the insights that CHMI trials have provided into early immune activation and regulation during acute infection, and the capacity to induce and maintain immunological memory. Importantly, these studies show that a single infection is sufficient to induce long-lasting parasite-specific T- and B-cell memory responses, and suggest that blood-stage induced regulatory responses can limit inflammation both in ongoing and potentially future infections. As future perspective of investigation in CHMIs, we discuss the role of innate cell subsets, the interplay between innate and adaptive immune activation and the potential modulation of these responses after natural pre-exposure. PMID- 26864136 TI - Immunomics: a 21st century approach to vaccine development for complex pathogens. AB - Immunomics is a relatively new field of research which integrates the disciplines of immunology, genomics, proteomics, transcriptomics and bioinformatics to characterize the host-pathogen interface. Herein, we discuss how rapid advances in molecular immunology, sophisticated tools and molecular databases are facilitating in-depth exploration of the immunome. In our opinion, an immunomics based approach presides over traditional antigen and vaccine discovery methods that have proved ineffective for highly complex pathogens such as the causative agents of malaria, tuberculosis and schistosomiasis that have evolved genetic and immunological host-parasite adaptations over time. By using an integrative multidisciplinary approach, immunomics offers enormous potential to advance 21st century antigen discovery and rational vaccine design against complex pathogens such as the Plasmodium parasite. PMID- 26864137 TI - Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress. AB - Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down regulation of liver CoA pools in sCSDS mice. PMID- 26864138 TI - Role of Sirolimus in Advanced Kaposiform Hemangioendothelioma. AB - Kaposiform hemangioendothelioma (KHE) is an infiltrative vascular tumor that classically presents in infancy. Management typically focuses on treating Kasabach-Merritt phenomenon (KMP), a disorder of severe and at times life threatening platelet trapping. However, the morbidity of KHE extends beyond KMP. The infiltrative nature of the tumor can lead to long-term disability and often makes complete surgical resection impossible. We report the case of a 10-year-old boy with a KHE of his right distal thigh who was unable to walk without assistance due to fibrotic change and right knee contracture. He had no laboratory evidence of KMP at the time of representation. Rapamycin was started in hopes of reducing the tumor burden. Within 2 months of therapy, fibrotic areas softened, his contracture nearly resolved, and there was marked improvement in his mobility. Rapamycin has been previously reported to be effective in managing cases of KHE complicated by KMP. Our report emphasizes the role for rapamycin in the treatment of KHE in the absence of KMP through the inhibition of vasculogenesis and fibrotic pathways. PMID- 26864140 TI - Transcranial direct current stimulation associated with gait training in Parkinson's disease: A pilot randomized clinical trial. AB - OBJECTIVE: The aim of this study is to investigate the effects of transcranial direct current stimulation (tDCS) combined with cueing gait training (CGT) on functional mobility in patients with Parkinson's disease (PD). METHODS: A pilot double-blind controlled, randomized clinical trial was conducted with 22 patients with PD assigned to the experimental (anodal tDCS plus CGT) and control group (sham tDCS plus CGT). The primary outcome (functional mobility) was assessed by 10-m walk test, cadence, stride length, and Timed Up and Go test. Motor impairment, bradykinesia, balance, and quality of life were analyzed as secondary outcomes. Minimal clinically important differences (MCIDs) were observed when assessing outcome data. RESULTS: Both groups demonstrated similar gains in all outcome measures, except for the stride length. The number of participants who showed MCID was similar between groups. CONCLUSION: The CGT provided many benefits to functional mobility, motor impairment, bradykinesia, balance, and quality of life. However, these effect magnitudes were not influenced by stimulation, but tDCS seems to prolong the effects of cueing therapy on functional mobility. PMID- 26864139 TI - Sex differences in risk and heritability estimates on primary knee osteoarthritis leading to total knee arthroplasty: a nationwide population based follow up study in Danish twins. AB - BACKGROUND: Symptomatic knee osteoarthritis is a highly age and sex associated complex disease. Little is known about the causes behind this age and sex associated increase, or if genetic and environmental factors impacts differently by gender. Our study examined the risk and heritability of primary knee osteoarthritis leading to total knee arthroplasty and whether these differences were attributable to sex and age differences in heritability. METHODS: All twins of known zygosity from The Danish Twin Register alive in 1997 were examined in a nationwide population based follow-up study collecting information on all twins recorded in The Danish Knee Arthroplasty from 1997 to follow-up in 2010. Our main outcomes were the cumulative incidence, probandwise concordance rates, heritability, within pair correlations in monozygotic and dizygotic twin pairs and the genetic and environmental influence estimated in models taking into account that individuals may not have had a total knee arthroplasty at follow up. RESULTS: 92,748 twins were eligible for analyses and 576 twins had a record of primary knee osteoarthritis in The Danish Knee Arthroplasty Register at follow-up comprising 358 female and 218 male twin cases. The risk increased particular after the age of 50 years displaying significant sex differences in the elderly. In the sex stratified analyses a discrete genetic component was found in females, but in males no genetic component could be detected. In both genders common and unique environmental factors were highly significant. In the sex-adjusted analysis an additive genetic component of 18 % (0; 62), a shared environmental component of 61 % (25; 97) and an individual environmental component of 21 % (6; 36) accounted for the variation in liability to primary total knee arthroplasty. CONCLUSION: The risk of primary total knee arthroplasty increases significantly after the age of 50 years, in particular in females, displaying significant sex differences in the elderly. After sex-adjustment 82 % of the variation in liability to primary total knee arthroplasty was attributable to common and unique environmental factors; the remaining 18 % of this variation was attributable to additive genetic factors indicating a pivotal impact of environmental factors on this disease. PMID- 26864141 TI - A retrospective observational study for the outcomes of women presenting to a colposcopy clinic with a high-grade Pap smear - Implications for a 'see and treat' approach to management. AB - BACKGROUND: The current Australian National Health and Medical Research Council guidelines discourage the use of 'see and treat' colposcopic management due to concerns regarding over-treatment. However, this approach has been shown to have benefits in several studies, including cost savings, elimination of loss to follow up and decreased patient anxiety. AIMS: To provide Australian data on treatment outcomes for women presenting with a high-grade Pap smear to a large metropolitan colposcopy unit and to determine whether a 'see and treat' approach would meet specified standards. MATERIALS AND METHODS: Retrospective review of women referred to the Royal Prince Alfred Hospital colposcopy unit with a high grade smear. Patient data, colposcopy findings, treatment and pathology results were collated and analysed to determine treatment outcomes using the current 'biopsy and treat' approach. The feasibility of 'see and treat' was assessed by determining which women with high-grade colposcopy findings had high-grade disease confirmed on biopsy or excisional specimens. RESULTS: One hundred and thirty-seven women underwent either excisional or ablative treatment. Of those undergoing excisional procedures, 81.3% had high-grade dysplasia or invasive cancer, 11.6% had CIN1 and 7.1% had no dysplasia on histopathology. One hundred and twenty-one with high-grade colposcopy findings had histopathology results available. Using a 'see and treat' approach, 92.6% would have had confirmed dysplasia of any grade, while 91.7% had confirmed high-grade dysplasia. CONCLUSIONS: 'See and treat' colposcopy is feasible in the Australian setting when applied to selected patients with high-grade cytology and high-grade colposcopic findings. PMID- 26864142 TI - Confluent fibrosis and fibroblast foci in fibrotic non-specific interstitial pneumonia. AB - AIMS: The separation of fibrotic non-specific interstitial pneumonia (FNSIP) and usual interstitial pneumonia (UIP) is important for patient treatment and prognosis, but is sometimes a difficult diagnostic problem. Most authors believe that fibroblast foci are rare in NSIP, and that the finding of multiple fibroblast foci suggests a diagnosis of UIP. Similarly, architectural distortion is viewed as favouring a diagnosis of UIP. This study aims to assess these criteria for their diagnostic utility. METHODS AND RESULTS: We report eight patients with a high-resolution computed tomography diagnosis of FNSIP, and a picture of fibrotic NSIP on biopsy, but in whom, in all cases, fibrosis focally widened the walls to the point of confluence, producing architectural distortion in the form of variably sized, sometimes quite large, blocks of fibrosis, but not honeycombing. Fibroblast foci varied from four to nine per section, and point counting morphometry showed that the areas containing large blocks of confluent fibrosis were geographically strongly associated with fibroblast foci, whereas fibroblast foci were rare away from the confluent fibrosis. Follow-up imaging studies (mean interval 19.5 months; range 2-42 months) in six patients revealed stable or improved disease in four and worsening disease in two. No case had or developed radiological honeycombing, and there were no other imaging findings to suggest a diagnosis of UIP. CONCLUSIONS: Otherwise typical FNSIP cases can show architectural distortion caused by confluence or marked expansion of fibrotic alveolar walls. These areas tend to be associated with fibroblast foci. These findings do not imply a poor prognosis, and should not be confused with UIP. PMID- 26864144 TI - C15043. Chemical Constituents of Plants from the Genus Phlegmariurus. AB - Phlegmariurus is a genus of ca. 200 species in the family Huperziaceae, mainly distributing in tropical and subtropical Asia, with 23 species being endemic to South China [1]. The whole plants of several species of Phlegmariurus genus have been used in traditional Chinese medicine. For example, P. phlegmaria (L.) Holub was used for the treatment of rheumatic pain, arthritis, traumatic injury, sore throat, edema and urticaria [2]. Since huperzine A, a potent, reversible and selective acetylcholinesterase inhibitor and a promising drug for the treatment of symptoms of Alzheimer's disease was discovered from Huperzia serrata (Thunb. Ex Murray) Trev. (Huperziaceae), numerous efforts on the isolation of new potent alkaloids from H. serrata and related plants have been carried out by many research groups, which led to the isolation of a series of plant constituents, especially lycopodium alkaloids with diverse structures of many unusual skeletons of interest from biogenetic and biological points of view and challenging targets for total synthesis [3-8]. This article is protected by copyright. All rights reserved. PMID- 26864143 TI - Mapping forests in monsoon Asia with ALOS PALSAR 50-m mosaic images and MODIS imagery in 2010. AB - Extensive forest changes have occurred in monsoon Asia, substantially affecting climate, carbon cycle and biodiversity. Accurate forest cover maps at fine spatial resolutions are required to qualify and quantify these effects. In this study, an algorithm was developed to map forests in 2010, with the use of structure and biomass information from the Advanced Land Observation System (ALOS) Phased Array L-band Synthetic Aperture Radar (PALSAR) mosaic dataset and the phenological information from MODerate Resolution Imaging Spectroradiometer (MOD13Q1 and MOD09A1) products. Our forest map (PALSARMOD50 m F/NF) was assessed through randomly selected ground truth samples from high spatial resolution images and had an overall accuracy of 95%. Total area of forests in monsoon Asia in 2010 was estimated to be ~6.3 * 10(6 )km(2). The distribution of evergreen and deciduous forests agreed reasonably well with the median Normalized Difference Vegetation Index (NDVI) in winter. PALSARMOD50 m F/NF map showed good spatial and areal agreements with selected forest maps generated by the Japan Aerospace Exploration Agency (JAXA F/NF), European Space Agency (ESA F/NF), Boston University (MCD12Q1 F/NF), Food and Agricultural Organization (FAO FRA), and University of Maryland (Landsat forests), but relatively large differences and uncertainties in tropical forests and evergreen and deciduous forests. PMID- 26864145 TI - Technical mentorship during robot-assisted surgery: a cognitive analysis. AB - OBJECTIVE: To investigate cognitive and mental workload assessments, which may play a critical role in defining successful mentorship. MATERIALS AND METHODS: The 'Mind Maps' project aimed at evaluating cognitive function with regard to surgeon's expertise and trainee's skills. The study included electroencephalogram (EEG) recordings of a mentor observing trainee surgeons in 20 procedures involving extended lymph node dissection (eLND) or urethrovesical anastomosis (UVA), with simultaneous assessment of trainees using the National Aeronautics and Space Administration Task Load index (NASA-TLX) questionnaire. We also compared the brain activity of the mentor during this study with his own brain activity while actually performing the same surgical steps from previous procedures populated in the 'Mind Maps' project. RESULTS: During eLND and UVA, when the mentor thought the trainee's mental demand and effort were low based on his NASA-TLX questionnaire (not satisfied with his performance), his EEG-based mental workload increased (reflecting more concern and attention). The mentor was mentally engaged and concerned while he was engrossed in observing the surgery. This was further supported by the finding that there was no significant difference in the mental demands and workload between observing and operating for the expert surgeon. CONCLUSIONS: This study objectively evaluated the cognitive engagement of a surgical mentor teaching technical skills during surgery. The study provides a deeper understanding of how surgical teaching actually works and opens new horizons for assessment and teaching of surgery. Further research is needed to study the feasibility of this novel concept in assessment and guidance of surgical performance. PMID- 26864146 TI - Bone-anchored hearing aid and skin graft removal with subsequent cochlear implantation. AB - We describe a novel technique of scalp flap rearrangement for cochlear implant (CI) candidates who have previously undergone ipsilateral bone-anchored hearing aid (BAHA) placement. One patient with single-sided deafness (SSD) underwent removal of a BAHA with subsequent scalp rearrangement for coverage of the implant site. After adequate healing of the scalp rotational flap, he underwent uncomplicated cochlear implantation without soft tissue complications. With increasing utilization of CIs in SSD, there will be more patients undergoing cochlear implantation who have previously had a BAHA. We present a novel method for accomplishing this goal while minimizing the risk of soft tissue complications. Laryngoscope, 126:2601-2604, 2016. PMID- 26864147 TI - In Situ Mitigation of Subsurface and Peripheral Focused Ion Beam Damage via Simultaneous Pulsed Laser Heating. AB - Focused helium and neon ion (He(+)/Ne(+)) beam processing has recently been used to push resolution limits of direct-write nanoscale synthesis. The ubiquitous insertion of focused He(+)/Ne(+) beams as the next-generation nanofabrication tool-of-choice is currently limited by deleterious subsurface and peripheral damage induced by the energetic ions in the underlying substrate. The in situ mitigation of subsurface damage induced by He(+)/Ne(+) ion exposures in silicon via a synchronized infrared pulsed laser-assisted process is demonstrated. The pulsed laser assist provides highly localized in situ photothermal energy which reduces the implantation and defect concentration by greater than 90%. The laser assisted exposure process is also shown to reduce peripheral defects in He(+) patterned graphene, which makes this process an attractive candidate for direct write patterning of 2D materials. These results offer a necessary solution for the applicability of high-resolution direct-write nanoscale material processing via focused ion beams. PMID- 26864148 TI - Modelling energy efficiency of an integrated anaerobic digestion and photodegradation of distillery effluent using response surface methodology. AB - Anaerobic digestion (AD) is efficient in organic load removal and bioenergy recovery when applied in treating distillery effluent; however, it is ineffective in colour reduction. In contrast, ultraviolet (UV) photodegradation post treatment for the AD-treated distillery effluent is effective in colour reduction but has high energy requirement. The effects of operating parameters on bioenergy production and energy demand of photodegradation were modelled using response surface methodology (RSM) with a view of developing a sustainable process in which the biological step could supply energy to the energy-intensive photodegradation step. The organic loading rate (OLRAD) and hydraulic retention time (HRTAD) of the initial biological step were the variables investigated. It was found that the initial biological step removed about 90% of COD and only about 50% colour while photodegradation post-treatment removed 98% of the remaining colour. Maximum bioenergy production of 180.5 kWh/m(3) was achieved. Energy demand of the UV lamp was lowest at low OLRAD irrespective of HRTAD, with values ranging between 87 and 496 kWh/m(3). The bioenergy produced formed 93% of the UV lamp energy demand when the system was operated at OLRAD of 3 kg COD/m(3) d and HRT of 20 days. The presumed carbon dioxide emission reduction when electricity from bioenergy was used to power the UV lamp was 28.8 kg CO2 e/m(3), which could reduce carbon emission by 31% compared to when electricity from the grid was used, leading to environmental conservation. PMID- 26864149 TI - Rosmarinic acid inhibits some metabolic enzymes including glutathione S transferase, lactoperoxidase, acetylcholinesterase, butyrylcholinesterase and carbonic anhydrase isoenzymes. AB - Rosmarinic acid (RA) is a natural polyphenol contained in many aromatic plants with promising biological activities. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates. Acetylcholinesterase (AChE, E.C. 3.1.1.7) is intimately associated with the normal neurotransmission by catalysing the hydrolysis of acetylcholine to acetate and choline and acts in combination with butyrylcholinesterase (BChE) to remove acetylcholine from the synaptic cleft. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms, whereas glutathione S transferases (GSTs) are dimeric proteins present both in prokaryotic and in eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effects of rosmarinic acid on tumour-associated carbonic anhydrase IX and XII isoenzymes, AChE, BChE, LPO and GST enzymes were evaluated. Rosmarinic acid inhibited these enzymes with Kis in the range between micromolar to picomolar. The best inhibitory effect of rosmarinic acid was observed against both AChE and BChE. PMID- 26864150 TI - Description of the Halophile Euplotes qatarensis nov. spec. (Ciliophora, Spirotrichea, Euplotida) Isolated from the Hypersaline Khor Al-Adaid Lagoon in Qatar. AB - The morphology, ontogenesis, and phylogenetic relationships of a halophile euplotid ciliates, Euplotes qatarensis nov. spec., isolated from the Khor Al Adaid Lagoon in Qatar were investigated based on live observation as well as protargol- and silver nitrate-impregnated methods. The new species is characterised by a combination of features: the halophile habitat, a cell size of 50-65 * 33-40 MUm, seven dorsal ridges, 10 commonly sized frontoventral cirri, two widely spaced marginal cirri, 10 dorsolateral kineties, and a double silverline pattern. The morphogenesis is similar to that of its congeners: (i) the oral primordium develops hypoapokinetally and the parental oral apparatus is retained; (ii) the frontoventral-transverse field of five streaks gives rise to the frontal, ventral, and transverse cirri, but not to the cirri I/1 and the marginal cirri; (iii) the dorsal somatic ciliature develops by intrakinetal proliferation of basal bodies in two anlagen per kinety that are just anterior and posterior to the future division furrow; (iv) the caudal cirri are formed by the two rightmost dorsolateral kineties. The SSU rDNA sequence of E. qatarensis branches with full support in the Euplotopsis elegans-Euplotes nobilii Euplotopsis raikovi clade. The closest related publicly available SSU rDNA sequence is the one of E. nobilii, with which E. qatarensis has 93.4% sequence similarity. Euplotes parawoodruffi Song & Bradbury, 1997 is transferred to the genus Euplotoides based on the absence of frontoventral cirrus VI/3. PMID- 26864151 TI - Mechanistic investigation of the on-surface enzymatic digestion (oSED) protein adsorption detection method using targeted mass spectrometry. AB - This study describes our efforts to study some of the mechanistic aspects of the earlier established on-surface enzymatic digestion (oSED) method. In a multitude of application areas, it has become important to be able to fully characterize and understand selective protein adsorption to biomaterial surfaces for various applications, including biomedicine (implants), nanotechnology (microchip surfaces and sensors) and materials sciences. Herein, the investigation of the mechanistic aspects was based on microdialysis catheter tubes that were flushed with controlled protein solutions mimicking the extracellular fluid of the brain. The protein adsorption properties were monitored using high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) with a targeted method. The temporally resolved results show that most proteins stay adsorbed onto the surface during the entire digestion process and are only cut away piece by piece, whereas smaller proteins and peptides seem to desorb rather easily from the surface. This information will simplify the interpretation of data generated using the oSED method and can also be used for the characterization of the physicochemical properties controlling the adsorption of individual proteins to specific surfaces. PMID- 26864154 TI - Delayed Presentation of Aortic Injury by a Thoracic Pedicle Screw. AB - Delayed presentation of a thoracic aortic injury is an extremely rare complication after spine surgery. We report a case of delayed presentation of a thoracic aortic injury with a vertebral pedicle screw after posterior spinal surgery without periaortic hematoma, hemorrhage or pseudoaneurysm formation and review the relevant literature. PMID- 26864152 TI - Years of life that could be saved from prevention of hepatocellular carcinoma. AB - BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986 1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour >= 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost. PMID- 26864153 TI - A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment experienced Korean patients chronically infected with genotype 2 hepatitis C virus. AB - In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection. PMID- 26864155 TI - Solubility parameter-based screening methods for early-stage formulation development of itraconazole amorphous solid dispersions. AB - OBJECTIVES: This article uses conventional and newly extended solubility parameter (delta) methods to identify polymeric materials capable of forming amorphous dispersions with itraconazole (itz). METHODS: Combinations of itz and Soluplus, Eudragit E PO (EPO), Kollidon 17PF (17PF) or Kollidon VA64 (VA64) were prepared as amorphous solid dispersions using quench cooling and hot melt extrusion. Storage stability was evaluated under a range of conditions using differential scanning calorimetry and powder X-ray diffraction. KEY FINDINGS: The rank order of itz miscibility with polymers using both conventional and novel delta-based approaches was 17PF > VA64 > Soluplus > EPO, and the application of the Flory-Huggins lattice model to itz-excipient binary systems corroborated the findings. The solid-state characterisation analyses of the formulations manufactured by melt extrusion correlated well with pre-formulation screening. Long-term storage studies showed that the physical stability of 17PF/vitamin E TPGS-itz was poor compared with Soluplus and VA64 formulations, and for EPO/itz systems variation in stability may be observed depending on the preparation method. CONCLUSION: Results have demonstrated that although delta-based screening may be useful in predicting the initial state of amorphous solid dispersions, assessment of the physical behaviour of the formulations at relevant temperatures may be more appropriate for the successful development of commercially acceptable amorphous drug products. PMID- 26864156 TI - Reduction in radiation doses from paediatric CT scans in Great Britain. AB - OBJECTIVE: Although CT scans provide great medical benefits, concerns have been raised about the magnitude of possible associated cancer risk, particularly in children who are more sensitive to radiation than adults. Unnecessary high doses during CT examinations can also be delivered to children, if the scan parameters are not adjusted for patient age and size. We conducted the first survey to directly assess the trends in CT scan parameters and doses for paediatric CT scans performed in Great Britain between 1978 and 2008. METHODS: We retrieved 1073 CT film sets from 36 hospitals. The patients were 0-19 years old, and CT scans were conducted between 1978 and 2008. We extracted scan parameters from each film including tube current-time product [milliampere seconds (mAs)], tube potential [peak kilovoltage (kVp)] and manufacturer and model of the CT scanner. We estimated the mean mAs for head and trunk (chest and abdomen/pelvis) scans, according to patient age (0-4, 5-9, 10-14 and 15-19 years) and scan year (<1990, 1990-1994, 1995-1999 and >=2000), and then derived the volumetric CT dose index and estimated organ doses. RESULTS: For head CT scans, mean mAs decreased by about 47% on average from before 1990 to after 2000, with the decrease starting around 1990. The mean mAs for head CTs did not vary with age before 1990, whereas slightly lower mAs values were used for younger patients after 1990. Similar declines in mAs were observed for trunk CTs: a 46% decline on an average from before 1990 to after 2000. Although mean mAs for trunk CTs did not vary with age before 1990, the value varied markedly by age, from 63 mAs for age 0-4 years compared with 315 mAs for those aged >15 years after 2000. No material changes in kVp were found. Estimated brain-absorbed dose from head CT scans decreased from 62 mGy before 1990 to approximately 30 mGy after 2000. For chest CT scans, the lung dose to children aged 0-4 years decreased from 28 mGy before 1990 to 4 mGy after 2000. CONCLUSION: We found that mAs for head and trunk CTs was approximately halved starting around 1990, and age-specific mAs was generally used for paediatric scans after this date. These changes will have substantially reduced the radiation exposure to children from CT scans in Great Britain. ADVANCES IN KNOWLEDGE: The study shows that mAs and major organ doses for paediatric CT scans in Great Britain began to decrease around 1990. PMID- 26864157 TI - The Relationship Between Intolerance of Uncertainty, Sensory Sensitivities, and Anxiety in Autistic and Typically Developing Children. AB - Guided by a recent theory that proposes fundamental differences in how autistic individuals deal with uncertainty, we investigated the extent to which the cognitive construct 'intolerance of uncertainty' and anxiety were related to parental reports of sensory sensitivities in 64 autistic and 85 typically developing children aged 6-14 years. Intolerance of uncertainty and anxiety explained approximately half the variance in autistic children's sensory sensitivities, but only around a fifth of the variance in typical children's sensory sensitivities. In children with autism only, intolerance of uncertainty remained a significant predictor of children's sensory sensitivities once the effects of anxiety were adjusted for. Our results suggest intolerance of uncertainty is a relevant construct to sensory sensitivities in children with and without autism. PMID- 26864158 TI - An Evaluation of a Parent Implemented In Situ Pedestrian Safety Skills Intervention for Individuals with Autism. AB - This study evaluated an in situ pedestrian safety skills intervention for three individuals with autism , as implemented by their parents. Specifically, this study examined the utility of behavioral skills training (BST) in helping parents implement most-to-least prompting procedures in training their children to use pedestrian safety skills in community settings. A multiple baseline design across participants was used to assess parent implementation of in situ pedestrian safety skills training as well as the correct use of safety skills independently by the participating individuals with autism. Results indicated that parents implemented in situ, most-to-least prompting procedures with high levels of accuracy across street locations during intervention and fading of BST. All child participants significantly improved their pedestrian safety skills during intervention across all natural street settings. For all three participants, the acquired skills were maintained above baseline levels at 1-month follow-up. PMID- 26864159 TI - Evidence of Reduced Global Processing in Autism Spectrum Disorder. AB - Frith's original notion of 'weak central coherence' suggested that increased local processing in autism spectrum disorder (ASD) resulted from reduced global processing. More recent accounts have emphasised superior local perception and suggested intact global integration. However, tasks often place local and global processing in direct trade-off, making it difficult to determine whether group differences reflect reduced global processing, increased local processing, or both. We present two measures of global integration in which poor performance could not reflect increased local processing. ASD participants were slower to identify fragmented figures and less sensitive to global geometric impossibility than IQ-matched controls. These findings suggest that reduced global integration comprises one important facet of weak central coherence in ASD. PMID- 26864160 TI - Infant Development in Fragile X Syndrome: Cross-Syndrome Comparisons. AB - This study examined the developmental profile of male infants with fragile X syndrome (FXS) and its divergence from typical development and development of infants at high risk for autism associated with familial recurrence (ASIBs). Participants included 174 boys ranging in age from 5 to 28 months. Cross sectional profiles on the Mullen Scales of Early Learning indicated infants with FXS could be differentiated from typically developing infants and ASIBs by 6 months of age. Infants with FXS displayed a trend of lower developmental skills with increasing age that was unique from the typically developing and ASIB groups. Findings suggest infants with FXS present with more significant, pervasive and early emerging delays than previously reported with potentially etiologically distinct developmental profiles. PMID- 26864162 TI - Six-month outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in treating single de novo lesions in human coronary artery. AB - OBJECTIVE: We aimed to investigate short-term outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in human coronary artery. BACKGROUND: Bioresorbable scaffolds are considered to be the fourth milestone in percutaneous coronary intervention. METHODS: Thirty patients with symptomatic ischemic coronary disease were enrolled and treated with the XINSORB scaffolds that were 3.0 * 12, 15, and 18 mm in size. The primary angiographic endpoint was late luminal loss (LLL), whereas the primary clinical endpoint was major adverse cardiac events (MACEs) at the 6 month follow-up. In a subset of 19 patients, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed at follow-up. RESULTS: The success rates of the procedure and the device were both 100%. Twenty-seven patients received angiographic follow-up. All patients were clinically assessed. Neither MACEs nor stent thrombus-related events were recorded. The percentage of diameter stenosis at follow-up was similar to that at postprocedure. In-scaffold and periscaffold LLL were 0.17 +/- 0.12 and 0.13 +/- 0.24 mm, respectively. No in-stent restenosis was detected. IVUS showed that the mean areas of the lumen, scaffold, and neointima at follow up were 6.27 +/- 0.69, 6.48 +/- 0.70, and 0.20 +/- 0.09 mm(2) , while in-device stenosis was 3.1 +/- 1.3%. OCT showed that 97.9% of the struts presented a preserved box, while 2.1% had an open box after 6 months. A total of 95.9% of the struts were covered by neointima. CONCLUSIONS: This first-in-human study demonstrates the effectiveness and safety of the XINSORB scaffold in treating single de novo coronary lesions. PMID- 26864163 TI - Is the use of maternal healthcare among prospective mothers higher in households that have experienced maternal death? Evidence from India. AB - Essential maternity care services include providing antenatal, delivery and postnatal care in a continuum to avert excess maternal deaths. This study assesses whether there is any significant difference in the utilization of maternal healthcare services between women from households that experienced any maternal death and women from households that did not experience any maternal death. Data from India's District Level Households and Facility Survey, 2007-08 were used. A sample of 321 women (unweighted) aged 15-49 years residing in households that had experienced maternal death, and 217 737 women (unweighted) of the same age group living in households that did not experience any maternal death were found eligible for the analysis. Results indicate that women belonging to households that experienced maternal deaths were less likely to opt for full antenatal care [odds ratio (OR): 0.56; 95% confidence interval (CI): 0.35-0.88] and postnatal care (OR: 0.82; 95% CI: 0.61-0.91) compared with women from households that did not experience any maternal death. Conversely, women belonging to households experiencing maternal deaths were more likely to utilize skilled birth attendants (OR: 1.31; 95% CI: 1.03-1.73) for their last delivery. This study hopes to draw the attention of program and policy makers to improve the reach of antenatal and postnatal care services, which are considered to be a supply side barrier compared with institutional delivery even by households that have reported maternal death. PMID- 26864164 TI - Friendship Award: J. S. Siegel and P. J. Stang / International Science and Technology Cooperation Award: P. J. Stang / Gay-Lussac Humboldt Prize: M. Antonietti and S. Schlemmer. PMID- 26864161 TI - Serum microRNAs as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. AB - The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0.70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR 222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC. PMID- 26864166 TI - Nazarov cyclization of divinyl ketones bearing an ester group at the beta position: a remarkable effect of alpha-substitution and alkene geometry on regioselectivity. AB - The Nazarov cyclization of divinyl ketones with an ester at the beta-position was examined with particular reference to where the cyclic double bond forms. We observed unprecedented regioselectivity, dictated by the subtle substitution patterns at the alpha-position and alkene geometry of alpha,beta and mostly, this selectivity is regardless of substitutions at alpha'- and beta'-positions. The major implications of these observations are an aromatic group at the alpha position with E-olefin geometry provides a cyclopentenone in which the double bond is not in conjugation with an ester, whereas Z-olefin provides a cyclopentenone in which the double bond is in conjugation with an ester; and divinyl ketones bearing an ester group at the beta-position and an alkyl group at the alpha-position with E-olefin geometry provide a cyclopentenone in which the double bond is in conjugation with the ester. PMID- 26864165 TI - Efficacy of a Required Preoperative Weight Loss Program for Patients Undergoing Bariatric Surgery. AB - The efficacy of mandatory medically supervised preoperative weight loss (MPWL) prior to bariatric surgery continues to be a controversial topic. The purpose of this observational study was to assess the efficacy of a MPWL program in a single institution, which mandated at least 10% excess body weight loss before surgery, by comparing outcomes of patients undergoing primary bariatric surgery with and without a compulsory preoperative weight loss regimen. We analyzed our database of 757 patients who underwent primary bariatric surgery between March 2008 and January 2015. Patients were placed into two cohorts based on their participation in a MPWL program requiring at least 10% excess weight loss (EWL) prior to surgery. Patients were evaluated at 3, 6, 12, and 24 months after surgery for weight loss, comorbidity resolution, and the occurrences of hospital readmissions. A total of 717 patients met the inclusion criteria of whom 465 underwent surgery without a preoperative weight loss requirement and 252 participated in the MPWL program. One year after surgery, 67.1% of non participants and 62.5% of MPWL participants showed a resolution of at least one of five associated comorbidities (p = 0.45). Non-participants showed an average of 58.6% EWL, while MPWL participants showed 59.1% EWL at 1 year postoperatively (p = 0.84). Readmission rates, excluding those which were ulcer-related, at 30 days (3.4 vs. 6.40%, p = 0.11) and 90 days (9.9 vs. 7.5%, p = 0.29) postoperatively were not significantly different between the non-participants and MPWL patients, respectively. A mandatory preoperative weight loss program prior to bariatric surgery did not result in significantly greater %EWL or comorbidity resolution 1 year after surgery compared to patients not required to lose weight preoperatively. Additionally, the program did not result in significantly lower 30- or 90-day readmission rates for these patients. The value of a MPWL program must be weighed against the potential loss of bariatric surgery candidates. Patients who fail to lose 10% excess weight preoperatively are thus ineligible for a procedure from which they would otherwise benefit. Our data suggest these patients will have similar positive outcomes. PMID- 26864167 TI - Impact of gender on decisions to participate in faecal immunochemical test-based colorectal cancer screening: a qualitative study. AB - OBJECTIVE: Faecal immunochemical tests (FITs) are increasingly being used in population-based colorectal cancer-screening programmes. Uptake of FIT is lower in men than women; however, the reasons for this are not well understood. We aimed to explore gender differences in influences on decisions to participate in FIT screening. METHODS: This is a qualitative study using in-depth face-to-face interviews of four groups of screening invitees (male and female screening users and male and female screening non-users), purposively sampled from the database of a population-based FIT screening programme. Recruitment continued until saturation was reached. Interviews were audio recorded and transcribed verbatim. Thematic analysis using the framework approach was employed with the theoretical domains framework guiding analysis. RESULTS: Forty-seven screening invitees were interviewed. Six theoretical domains influenced screening uptake: 'environmental context and resources', 'beliefs about capabilities', 'beliefs about consequences', 'emotions', 'social influences' and 'knowledge'. Male non-users were often fatalistic, less knowledgeable and misinformed about cancer and FIT screening compared with other groups. Female non-users expressed negative attitudes, beliefs and emotions towards FIT screening, cancer, social influences and the medical profession and were over-confident about their health. CONCLUSIONS: Negative attitudes and emotions to screening dominated non-user decision-making but differed by gender. Opportunities to improve uptake in men and women exist. Greater national discussions on the benefits of FIT screening, and development of screening materials tackling negative attitudes and beliefs while recognising male/female differences, may improve screening uptake. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864168 TI - Augmentation of the Inotropic Effects of Dopamine Following Linezolid Administration in an Infant. AB - Although generally safe and effective, one of the unique properties of linezolid is its weak inhibitory effect on monoamine oxidase. As such, it may interact with other medications that act through the adrenergic or serotonergic systems, including selective-serotonin reuptake inhibitors and vasoactive agents. We present a 3-month-old infant who was being treated with dopamine to maintain mean arterial pressure during mechanical ventilation following viral-induced respiratory failure. Hypertension and tachycardia developed during the administration of linezolid on two separate occasions. The physiology of catecholamine metabolism is reviewed including the role of the monoamine oxidase system. The potential interaction between linezolid and vasoactive agents such as dopamine is discussed. PMID- 26864169 TI - Neural probe combining microelectrodes and a droplet-based microdialysis collection system for high temporal resolution sampling. AB - We propose a novel neural probe which combines microfluidic channels with recording and stimulation electrodes. The developed microfabrication approach enables the concentration of every active element such as electrodes and the sampling inlet in close proximity on the same surface. As a first approach, full functional validation is presented in this work (in vivo testing will be presented in the next study). Electrical characterization by impedance spectroscopy is performed in order to assess the electrode properties. An advanced experimental setup enabling the validation of the fluidic functions of the neural probe is also presented. It allowed the achievement of a high temporal resolution (170 ms) during sampling as a result of the integration of a T junction droplet generator inside the probe. The droplets reached a volume of 0.84 nL and are separated by a non-aqueous phase (perfluoromethyldecalin, PFD). This probe represents an innovative tool for neuroscientists as it can be implanted in precise brain structures while combining electrical stimulation with sampling at a high temporal resolution. PMID- 26864170 TI - Co-functionalized organic/inorganic hybrid ZnO nanorods as electron transporting layers for inverted organic solar cells. AB - In an unprecedented attempt, we present an interesting approach of coupling solution processed ZnO planar nanorods (NRs) by an organic small molecule (SM) with a strong electron withdrawing cyano moiety and the carboxylic group as binding sites by a facile co-functionalization approach. Direct functionalization by SMs (SM-ZnO NRs) leads to higher aggregation owing to the weaker solubility of SMs in solutions of ZnO NRs dispersed in chlorobenzene (CB). A prior addition of organic 2-(2-methoxyethoxy)acetic acid (MEA) over ZnO NRs not only inhibits aggregation of SMs over ZnO NRs, but also provides enough sites for the SM to strongly couple with the ZnO NRs to yield transparent SM-MEA-ZnO NRs hybrids that exhibited excellent capability as electron transporting layers (ETLs) in inverted organic solar cells (iOSCs) of P3HT:PC60BM bulk-heterojunction (BHJ) photoactive layers. A strongly coupled SM-MEA-ZnO NR hybrid reduces the series resistance by enhancing the interfacial area and tunes the energy level alignment at the interface between the (indium-doped tin oxide, ITO) cathode and BHJ photoactive layers. A significant enhancement in power conversion efficiency (PCE) was achieved for iOSCs comprising ETLs of SM-MEA-ZnO NRs (3.64%) advancing from 0.9% for pristine ZnO NRs, while the iOSCs of aggregated SM-ZnO NRs ETL exhibited a much lower PCE of 2.6%, thus demonstrating the potential of the co functionalization approach. The superiority of the co-functionalized SM-MEA-ZnO NRs ETL is also evident from the highest PCE of 7.38% obtained for the iOSCs comprising BHJ of PTB7-Th:PC60BM compared with extremely poor 0.05% for non functionalized ZnO NRs. PMID- 26864171 TI - Evaluation of the Aptima((r)) HIV-1 Quant Dx assay for HIV-1 RNA viral load detection and quantitation in plasma of HIV-1-infected individuals: A comparison with Abbott RealTime HIV-1 assay. AB - The Hologic Aptima((r)) HIV-1 Quant Dx assay (Aptima HIV) is a real-time transcription-mediated amplification method CE-approved for use in diagnosis and monitoring of HIV-1 infection. The analytical performance of this new assay was compared to the FDA-approved Abbott RealTime HIV-1 (RealTime). The evaluation was performed using 220 clinical plasma samples, the WHO 3rd HIV-1 International Standard, and the QCMD HIV-1 RNA EQA. Concordance on qualitative results, correlation between quantitative results, accuracy, and reproducibility of viral load data were analyzed. The ability to measure HIV-1 subtypes was assessed on the second WHO International Reference Preparation Panel for HIV-1 Subtypes. With clinical samples, inter-assay agreement for qualitative results was high (91.8%) with Cohen's kappa statistic equal to 0.836. For samples with quantitative results in both assays (n = 93), Lin's concordance correlation coefficient was 0.980 (P < 0.0001) and mean differences of measurement, conducted according to Bland-Altman method, was low (0.115 log10 copies/ml). The Aptima HIV quantified the WHO 3rd HIV-1 International Standard diluted from 2000 to 31 cp/ml (5,700-88 IU/ml) at expected values with excellent linearity (R(2) > 0.970) and showed higher sensitivity compared to RealTime being able to detect HIV-1 RNA in 10 out of 10 replicates containing down to 7 cp/ml (20 IU/ml). Reproducibility was very high, even at low HIV-1 RNA values. The Aptima HIV was able to detect and accurately quantify all the main HIV-1 subtypes in both reference panels and clinical samples. Besides excellent performance, Aptima HIV shows full automation, ease of use, and improved workflow compared to RealTime. J. Med. Virol. 88:1535-1544, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864172 TI - Localization and Classification of Paddy Field Pests using a Saliency Map and Deep Convolutional Neural Network. AB - We present a pipeline for the visual localization and classification of agricultural pest insects by computing a saliency map and applying deep convolutional neural network (DCNN) learning. First, we used a global contrast region-based approach to compute a saliency map for localizing pest insect objects. Bounding squares containing targets were then extracted, resized to a fixed size, and used to construct a large standard database called Pest ID. This database was then utilized for self-learning of local image features which were, in turn, used for classification by DCNN. DCNN learning optimized the critical parameters, including size, number and convolutional stride of local receptive fields, dropout ratio and the final loss function. To demonstrate the practical utility of using DCNN, we explored different architectures by shrinking depth and width, and found effective sizes that can act as alternatives for practical applications. On the test set of paddy field images, our architectures achieved a mean Accuracy Precision (mAP) of 0.951, a significant improvement over previous methods. PMID- 26864173 TI - The transformation of polyoxometalates in the formation of intercluster compound [Ag41(alpha-SiW(10)O37)((t)BuC=C)27(CH3CN)3][beta-SiW(12)O40]. AB - We report a unique intercluster compound comprising a Ag41 cage encapsulating a divacant [alpha-SiW(10)O37](10-) anion and a complete [beta-SiW(12)O40](4-) anion as a counteranion. Two electro-redox centers associated with the inner and outer POM anions show interesting electrochemical behaviours, because the stable Ag41 cage acts as an electron transfer mediator. PMID- 26864174 TI - Redesigning Care for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock-Reply. PMID- 26864175 TI - Zika Virus Infection in a Massachusetts Resident After Travel to Costa Rica: A Case Report. PMID- 26864176 TI - Building children's nursing for Africa. PMID- 26864177 TI - Training nurses to reduce child mortality. PMID- 26864178 TI - Children's rights education: An imperative for health professionals. AB - The South African government has put in place a range of laws, policies and programmes that are designed to give effect to children's rights and support children's survival, health and optimal development. These rights do not just exist on paper. They have the potential to transform professional practice and improve the quality of care across a range of health care services. A child rights' approach requires nurses to act in the best interest of children, respect their evolving capacities, think more holistically about a child's well-being and work with others to address the broader social determinants of health--such as access to food, water and sanitation. This article draws on lessons learned from a short course in children's rights and child law for health professionals offered by the Children's Institute, University of Cape Town from 2011-2014. It encourages nurses to reflect critically on their current practice and to take action to improve a child's well-being. It also advocates for the inclusion of children's rights to be at the heart of education and training, professional codes of conduct and standards of care. PMID- 26864179 TI - Improving the quality of nursing documentation: An action research project. AB - BACKGROUND: Documentation is an important function of professional nursing practise. In spite of numerous improvement efforts globally, inadequate documentation continues to be reported as nurse authors investigate barriers and challenges. OBJECTIVES: The project aimed to improve nurses' documentation of their patient assessments at the CURE Children's Hospital of Uganda in order to enhance the quality of nursing practise. METHOD: An action research methodology, using repeated cycles of planning, intervention, reflection and modification, was used to establish best practise approaches in this context for improving nurses' efficacy in documenting assessments in the patient record. The researchers gathered data from chart audits, literature reviews and key informant interviews. Through analysis and critical reflection, these data informed three cycles of systems and practise modifications to improve the quality of documentation. RESULTS: The initial cycle revealed that staff training alone was insufficient to achieve the project goal. To achieve improved documentation, broader changes were necessary, including building a critical mass of competent staff, redesigned orientation and continuing education, documentation form redesign, changes in nurse skill mix, and continuous leadership support. CONCLUSION: Improving nursing documentation involved complex challenges in this setting and demanded multiple approaches. Evidence-based practise was the foundation of changes in systems required to produce visible improvement in practise. The involved role of leadership in these efforts was very important. PMID- 26864180 TI - Journal club: Integrating research awareness into postgraduate nurse training. AB - BACKGROUND: Evidence-based nursing requires nurses to maintain an awareness of recently published research findings to integrate into their clinical practice. In the South African setting keeping up with recent literature has additional challenges, including the diversity of nurses' home language, geographically foreign origins of published work, and limited economic resources. Students enrolled in a postgraduate programme came from various paediatric settings and displayed limited awareness of nursing literature as an evidence base for practice. OBJECTIVES: The study aimed to design and introduce a journal club as an educational strategy into the postgraduate programmes in children's nursing at the University of Cape Town (UCT), and then to refine the way it is used to best serve programme outcomes and facilitate student learning whilst still being an enjoyable activity. METHOD: An action research methodology using successive cycles of 'assess-plan-act-observe' was used to design, implement and refine the structure of a journal club within the postgraduate diploma programme over four academic years. Six educators actively tracked and reflected on journal club sessions, and then analysed findings during and after each annual cycle to plan improvement and increasing programme alignment. RESULTS: Considerable refinement of the intervention included changing how it was structured, the preparation required by both students and educators, the article selection process and the intervention's alignment with other learning activities in the programme. CONCLUSION: Journal club facilitated an increase in student awareness and reading of nursing literature, offering the opportunity to consider application of published research to current nursing practice. Another benefit was enabling students to become familiar with the specialised and technical language of research, children's nursing and the critical care of children and neonates, by speaking about these in peer settings. PMID- 26864181 TI - Knowledge, attitudes and practices of neonatal staff concerning neonatal pain management. AB - BACKGROUND: Neonatal pain management has received increasing attention over the past four decades. Research into the effects of neonatal pain emphasises the professional, ethical and moral obligations of staff to manage pain for positive patient outcomes. However, evaluation studies continuously report evidence of inadequate neonate pain management and a gap between theory and practice. OBJECTIVE: This study reviewed current practice in neonatal pain management to describe the knowledge, attitudes and practices of nurses and doctors regarding pain management for neonates in two academic hospitals. METHOD: A non experimental, prospective quantitative survey, the modified Infant Pain Questionnaire, was used to collect data from 150 nurses and doctors working in the neonatal wards of two academic hospitals in central Gauteng. RESULTS: The response rate was 35.33% (n=53), most respondents being professional nurses (88.68%; n=47) working in neonatal intensive care units (80.77%; n=42); 24 (45.28%) had less than 5 years' and 29 respondents 6 or more years' working experience in neonatal care. A review of pain management in the study setting indicated a preference for pharmacological interventions to relieve moderate to severe pain. An association (p<0.05) was found between pain ratings on 5 procedures and frequency of administration of pharmacological pain management. Two-thirds of respondents (64%) reported that there were no pain management guidelines in the neonatal wards in which they worked. CONCLUSION: The interventions to manage moderate neonatal pain are in line with international guidelines. However, neonatal pain management may not occur systematically based on prior assessment of neonatal pain, choice of most appropriate intervention and evaluation. This study recommends implementation of a guideline to standardise practice and ensure consistent and adequate pain management in neonates. PMID- 26864184 TI - Hexadecapolar colloids. AB - Outermost occupied electron shells of chemical elements can have symmetries resembling that of monopoles, dipoles, quadrupoles and octupoles corresponding to filled s-, p-, d- and f-orbitals. Theoretically, elements with hexadecapolar outer shells could also exist, but none of the known elements have filled g orbitals. On the other hand, the research paradigm of 'colloidal atoms' displays complexity of particle behaviour exceeding that of atomic counterparts, which is driven by DNA functionalization, geometric shape and topology and weak external stimuli. Here we describe elastic hexadecapoles formed by polymer microspheres dispersed in a liquid crystal, a nematic fluid of orientationally ordered molecular rods. Because of conically degenerate boundary conditions, the solid microspheres locally perturb the alignment of the nematic host, inducing hexadecapolar distortions that drive anisotropic colloidal interactions. We uncover physical underpinnings of formation of colloidal elastic hexadecapoles and describe the ensuing bonding inaccessible to elastic dipoles, quadrupoles and other nematic colloids studied previously. PMID- 26864185 TI - Cardiac varix of the left ventricle causing outflow tract obstruction. PMID- 26864183 TI - Motion correction in MRI of the brain. AB - Subject motion in MRI is a relevant problem in the daily clinical routine as well as in scientific studies. Since the beginning of clinical use of MRI, many research groups have developed methods to suppress or correct motion artefacts. This review focuses on rigid body motion correction of head and brain MRI and its application in diagnosis and research. It explains the sources and types of motion and related artefacts, classifies and describes existing techniques for motion detection, compensation and correction and lists established and experimental approaches. Retrospective motion correction modifies the MR image data during the reconstruction, while prospective motion correction performs an adaptive update of the data acquisition. Differences, benefits and drawbacks of different motion correction methods are discussed. PMID- 26864187 TI - Peripheral pulmonary artery stenoses in the setting of Moyamoya. PMID- 26864186 TI - EACVI/EHRA Expert Consensus Document on the role of multi-modality imaging for the evaluation of patients with atrial fibrillation. AB - Atrial fibrillation (AF) is the commonest cardiac rhythm disorder. Evaluation of patients with AF requires an electrocardiogram, but imaging techniques should be considered for defining management and driving treatment. The present document is an expert consensus from the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association. The clinical value of echocardiography, cardiac magnetic resonance (CMR), computed tomography (CT), and nuclear imaging in AF patients are challenged. Left atrial (LA) volume and strain in echocardiography as well as assessment of LA fibrosis in CMR are discussed. The value of CT, especially in planning interventions, is highlighted. Fourteen consensus statements have been reached. These may serve as a guide for both imagers and electrophysiologists for best selecting the imaging technique and for best interpreting its results in AF patients. PMID- 26864188 TI - Anomalous papillary muscle insertion in hypertrophic cardiomyopathy. PMID- 26864189 TI - Combined thrombin and autologous blood for repair of lumbar durotomy. AB - Lumbar durotomy can be intended or unintended and can result in persistent cerebrospinal fluid (CSF) leak. Several methods are used to manage this complication including bed rest and CSF diversion. In this study, we theorize that the use of thrombin-soaked gel foam together with autologous blood laid on the sutured dural tear can prevent persistent CSF leak. A retrospective review of the records of patients who underwent lumbar surgery and had an unintended dural tear with CSF leak, comparing the outcome of patients who were submitted to thrombin-soaked gel foam together with autologous blood (group A) to patients treated by subfacial drain, tight bandage, and bed rest (group B). A total of 1371 patients had lumbar surgery, of whom 131 had dural tear. Group A included 62 patients, while group B included 69 patients. 8.1 % of group A patients had CSF leak as compared to 17.4 % of group B patients at postoperative day 14. The incidence of postoperative CSF leak and duration of postoperative hospital stay were statistically lower in group A than in group B (p < 0.05). Combining thrombin and autologous blood for repair of lumbar durotomy is an effective and a relatively cheap way to decrease CSF leak in the early postoperative period as well as decreasing postoperative hospital stay. It also resulted in decreased complications rate in the late postoperative period. PMID- 26864191 TI - Interleukin-1 receptor antagonist (anakinra) for Schnitzler syndrome. AB - Schnitzler syndrome is a rare autoinflammatory disease, which is defined by the presence of two major criteria: chronic urticaria and monoclonal immunoglobulin M (IgM) or immunoglobulin G gammopathy, in combination with at least two additional minor criteria: recurrent fever, leukocytosis and/or elevated C-reactive protein (CRP), objective signs of abnormal bone remodelling and a neutrophilic infiltrate in skin biopsy. We report on a 68-year-old female patient with a 10-year medical history of chronic urticaria, recurrent fever, severe arthralgia and increased CRP. Over the years, multiple diagnostic investigations were performed without conclusive findings, and therapeutic attempts with anti-histamines and several immunosuppressive agents had failed. The decision to initiate monotherapy with interleukin-1 (IL-1) receptor antagonist was based on immunohistochemical detection of the abundance of IL-1beta positive cells in the patient's skin biopsy. After starting treatment with anakinra, disappearance of symptoms could be observed within 24 h. Discontinuation of the treatment resulted in a rapid relapse of the symptoms. Finally, already after the initiation of therapy with anakinra, the suspected diagnosis of Schnitzler syndrome could be confirmed by detection of IgM-gammopathy that was initially absent. PMID- 26864190 TI - [Human papillomavirus and squamous cell cancer of the head and neck region : Prognostic, therapeutic and prophylactic implications]. AB - Human papilloma viruses (HPV) are responsible for approximately half of all oropharyngeal squamous cell carcinomas (OPSCC) and incidence rates of HPV associated OPSCC continue to increase substantially. The defined viral carcinogenesis permits development of specific diagnostic, therapeutic, and prophylactic approaches. Laboratory identification of HPV-associated OPSCC may be achieved by p16(INK4a) immunohistochemistry combined with HPV DNA detection by polymerase chain reaction (PCR) using tumor tissue. Patients with HPV-associated OPSCC have a relatively good prognosis; therefore, the HPV status plays an important role in patient guidance. Due to the relatively favorable prognosis, ongoing studies are evaluating whether less rigorous therapy for HPV-positive patients results in equally good cure rates. The criteria for patient selection are, however, still uncertain. Particularly markers for detection of HPV-positive patients with a high risk of treatment failure are lacking. Besides tumor stage and comorbidities, distinct genomic, epigenetic, and immunologic alterations are prognostically relevant for HPV-associated OPSCC, and might be of predictive value. Furthermore, the characteristic molecular alterations suggest the possibility of novel vigilant and specific therapy approaches. These may be inhibitors of the phosphatidylinositol 3-kinase (PI3K) pathway, which is frequently activated in HPV-associated OPSCC, and immunotherapeutic methods, e. g., therapeutic vaccination. Although prophylactic HPV vaccinations may also prevent development of HPV-associated OPSCC, foreseeable effects on OPSCC incidence will be low, given the low vaccination rates in Germany. This highlights the fact that interdisciplinary research networks should enhance the necessary activities related to HPV-associated OPSCC. PMID- 26864192 TI - Pre-procedural ultrasonography and marking for neuraxial anesthesia: an observational study. PMID- 26864193 TI - Intraperitoneal ketorolac for post-cholecystectomy pain: a double-blind randomized-controlled trial. AB - PURPOSE: Ketorolac is a parenterally active nonsteroidal anti-inflammatory drug with localized anti-inflammatory properties. We examine the postoperative analgesic efficacy of locally administered intraperitoneal (IP) ketorolac compared with intravenous (IV) ketorolac during laparoscopic cholecystectomy. METHODS: With institutional ethics approval, 120 patients undergoing elective laparoscopic cholecystectomy were randomized to receive intraoperative 1) IP ketorolac 30 mg + intravenous saline (IP group), 2) intraperitoneal saline + IV ketorolac 30 mg (IV group), or 3) intraperitoneal saline + intravenous saline (Control group) under standardized anesthesia. The primary and secondary outcomes were postoperative fentanyl requirements in the postanesthesia care unit and the time to first analgesic request, respectively. Other outcomes examined included abdominal pain (at rest and with coughing), shoulder pain, nausea, vomiting, and any other postoperative complications. RESULTS: On average, patients receiving IP ketorolac required less (mean difference, 29 MUg; 95% confidence interval [CI], 2 to 56; P = 0.04) fentanyl than patients in the Control group but a similar (mean difference, 16 MUg; 95% CI, 12 to 43; P = 0.27) amount compared to patients in the IV group. There was an increase in the median (interquartile range [IQR]) time to first request in the IP group (43[30-52] min) compared with the Control group (35 [27-49]min; P = 0.04) but no difference between the IP group compared with the IV group (47 [40-75] min; P = 0.22). Shoulder pain and resting pain were reduced with IP and IV ketorolac compared with Control, but there was no difference between the IP and IV groups. No differences were observed in any other outcomes, side effects, or complications attributable to opioids or ketorolac at any time points. CONCLUSION: This study did not demonstrate any advantage for the off-label topical intraperitoneal administration of ketorolac in this surgical population. Intraperitoneal and IV ketorolac showed comparable analgesic efficacy following laparoscopic cholecystectomy. PMID- 26864194 TI - Monitoring recovery from rocuronium-induced neuromuscular block using acceleromyography at the trapezius versus the adductor pollicis muscle: an observational trial. AB - PURPOSE: Positioning for surgery can restrict access to the patient's hand, thereby limiting assessment of the response at the adductor pollicis muscle to ulnar nerve stimulation. We evaluated a novel site to assess neuromuscular block by stimulating the accessory nerve and measuring the acceleromyographic response at the trapezius muscle. METHODS: In this prospective non-blinded observational study, we assessed neuromuscular transmission in anesthetized adult female patients undergoing elective laparoscopic gynecological surgery. We performed the assessment by simultaneous recording acceleromyographic responses with the TOF Watch((r)) SX monitor at both the right adductor pollicis and left trapezius muscles. The neuromuscular block was achieved using rocuronium 0.3 mg.kg(-1), and the repeatability, time course, and limits of agreement (Bland-Altman) of responses were compared at the two recording sites. The primary endpoint was the 90% train-of-four (TOF) recovery time with other endpoints included the onset time of the block, maximum T1 depression, time to 25% T1 recovery, and recovery time course of the T1 response and TOF ratio. RESULTS: Thirty-six patients were enrolled with responses obtained from 27 subjects. The variability of baseline responses recorded at the trapezius muscle was larger than that recorded at the adductor pollicis muscle, as determined by their mean (SD) repeatability coefficients [twitch height T1, 6.1 (1.9)% and 4.2 (1.6)%, respectively; P = 0.001; TOF ratio, 6.2 (2.1)% and 4.3 (1.7)%, respectively; P = 0.001]. The recorded responses showed relatively narrow limits of agreement. The onset time of the block was 0.3 min earlier at the trapezius muscle than at the adductor pollicis muscle [2.3 (0.8) min and 2.6 (0.7) min, respectively; P = 0.007], with limits of agreement ranging from 1.6 min earlier to 1.0 min later. The time to 25% T1 recovery was 1.8 min earlier at the trapezius muscle than at the adductor pollicis muscle [18.2 (5.7) min and 20.0 (5.2) min, respectively; P = 0.039], with limits of agreement ranging from 11.1 min earlier to 7.5 min later. Additionally, the time to achieve 90% TOF ratio was 4.4 min earlier at the trapezius muscle than at the adductor pollicis muscle [32.6 (7.9) min and 37 (9.1) min, respectively; P = 0.004], with limits of agreement ranging from 18.4 min earlier to 9.7 min later. CONCLUSIONS: We conclude that recording evoked acceleromyographic responses at the trapezius muscle is an acceptable alternative when monitoring from the adductor pollicis muscle is compromised. Nevertheless, we caution that recording a 90% TOF response at the trapezius muscle may overestimate functional recovery from the neuromuscular blockade. This trial was registered at ClinicalTrials.gov identifier, NCT01849198. PMID- 26864195 TI - The E3 Ubiquitin Ligase CRL4 Regulates Proliferation and Progression Through Meiosis in Chinese Mitten Crab Eriocheir sinensis. AB - The Cullin-RING E3s are multisubunit ubiquitin ligases composed of a scaffold protein known as Cullin, a RING finger protein that regulates diverse cellular pathways; however, their contribution to male gonad development, especially the spermatogenesis of the Chinese mitten crab (Eriocheir sinensis), is not well understood. We identified five evolutionarily conserved Cullins from the transcriptome and genome ofE. sinensis that are potentially involved in regulating male gonad development. The aim of the current study was to determine the mechanisms of Cullin4's effects on spermatogenesis. We observed that Cullin4, p53, and proliferating cell nuclear antigen had a specific expression and localization in primary spermatocytes. We also investigated the accumulation of Cullin substrates by treatment with inhibitor of NEDD8-activating enzyme MLN4924 in vitro. Cell cycle inhibitors p27 and p21 accumulated significantly after 24 and 36 h, respectively. We speculated that p53-mediated spontaneous germ cell apoptosis acts as a quality control mechanism to eliminate defective germ cells and that the Cullin4 complex maintains p53, p21, and p27 homeostasis in primary spermatocytes to regulate spermatogenesis ofE. sinensis Given its widespread evolutionary conservation, Cullin4 may regulate germ line development similarly in other organisms. PMID- 26864196 TI - A Dual Role for Melatonin in Medaka Ovulation: Ensuring Prostaglandin Synthesis and Actin Cytoskeleton Rearrangement in Follicular Cells. AB - Understanding the direct effects of melatonin on vertebrate ovulation remains a challenge. The present study provides the first characterization of the role of melatonin in ovulation using the teleost medaka. The melatonin receptor antagonist luzindole inhibited in vitro follicle ovulation. In the preovulatory follicles, arylalkylamine N-acetyltransferase 1a and hydroxyindole-O methyltransferase 2, the enzymes responsible for melatonin synthesis, were expressed in the granulosa cells throughout the 24 h spawning cycle. The granulosa cells of the follicle also expressed the melatonin receptor 1a-a. An in vitro characterization study using medaka OLHNI-2 cells revealed that melatonin and luzindole act as an agonist and an antagonist, respectively, of the melatonin receptor. The intracellular cAMP levels in these cells were reduced after melatonin treatment. The expression of cytosolic phospholipase A2 group 4a (Pla2g4a), the enzyme producing arachidonic acid (cyclooxygenase-2 substrate), was inhibited in the granulosa cells in luzindole-treated follicles. Follicular prostaglandin E2 levels and in vitro follicle ovulation were suppressed in follicles isolated at 12 h prior to ovulation and incubated with the Pla2g4a inhibitor AACOCF3. The G-actin:F-actin ratios in follicular cells increased with approaching ovulation, but this increase was suppressed after luzindole treatment. The phosphorylation of moesin, an ezrin-radixin-moesin protein, was inhibited in the follicular cells in luzindole-treated follicles. These results indicate a dual role for melatonin in medaka ovulation: melatonin ensures prostaglandin E2 synthesis throughout the spawning cycle and induces actin cytoskeleton rearrangement in the follicular cells at ovulation. PMID- 26864197 TI - Changes in MicroRNA Expression During Maturation of the Bovine Corpus Luteum: Regulation of Luteal Cell Proliferation and Function by MicroRNA-34a. AB - The corpus luteum (CL) develops from the remnants of the ovulatory follicle and produces progesterone, required for maintenance of pregnancy in mammals. The differentiation of granulosal and thecal cells into luteal cells is accompanied by hypertrophy and hyperplasia of cells. As the CL matures, growth ceases and in ruminants, the tissue acquires the ability to undergo regression in response to prostaglandin F2alpha. The regulators of this transition are poorly understood. MicroRNA, which are posttranscriptional regulators of tissue development and function, are expressed in the CL. However, the pattern of their expression and their function during the transition from developing to functional CL is not known. The objectives of this study were to profile the expression of miRNA in developing versus mature bovine CL and determine effects of miRNA on bovine luteal cell survival and function. Knockdown of Drosha in midcycle (MC) luteal cells decreased progesterone and increased luteal cell apoptosis in the presence or absence of proinflammatory cytokines. Microarray analysis demonstrated that a greater number of miRNA were expressed in MC compared to D4 CL. Ingenuity pathway analysis (IPA) predicted that D4-specific miRNA regulate pathways related to carbohydrate metabolism, while MC-specific miRNA regulate pathways related to cell cycle and apoptosis signaling. Both predictions are consistent with a switch in the CL from a growing phase to a maintenance phase. One of the MC specific miRNA, miR-34a, was selected for further analysis. Increased concentrations of miR-34a in MC luteal cells resulted in decreased luteal cell proliferation, increased progesterone production, and inhibition of Notch1 and YY1 translation, but had no effect on luteal cell apoptosis. In conclusion, these data support a role for miRNA in general, and miR-34a in particular, in luteal formation and function. PMID- 26864198 TI - Trace Elements in Ovaries: Measurement and Physiology. AB - Traditionally, research in the field of trace element biology and human and animal health has largely depended on epidemiological methods to demonstrate involvement in biological processes. These studies were typically followed by trace element supplementation trials or attempts at identification of the biochemical pathways involved. With the discovery of biological molecules that contain the trace elements, such as matrix metalloproteinases containing zinc (Zn), cytochrome P450 enzymes containing iron (Fe), and selenoproteins containing selenium (Se), much of the current research focuses on these molecules, and, hence, only indirectly on trace elements themselves. This review focuses largely on two synchrotron-based x-ray techniques: X-ray absorption spectroscopy and x ray fluorescence imaging that can be used to identify the in situ speciation and distribution of trace elements in tissues, using our recent studies of bovine ovaries, where the distribution of Fe, Se, Zn, and bromine were determined. It also discusses the value of other techniques, such as inductively coupled plasma mass spectrometry, used to garner information about the concentrations and elemental state of the trace elements. These applications to measure trace elemental distributions in bovine ovaries at high resolutions provide new insights into possible roles for trace elements in the ovary. PMID- 26864199 TI - The effect of hypohydration on endothelial function in young healthy adults. AB - PURPOSE: Hypohydration has been suggested as a predisposing factor for several pathologies including cardiovascular diseases (CVD). While CVD are the leading cause of death worldwide, no study has investigated whether acute hypohydration affects endothelial function and cardiovascular function. METHODS: Ten young, healthy males participated in this crossover study (age: 24.3 +/- 2.3 year; weight: 80.8 +/- 5.3 kg; BMI: 24.3 +/- 0.4 kg m-2). Each subject completed two measurements of endothelial function by flow-mediated dilation (FMD) in euhydrated and hypohydrated state separated by 24 h. Following baseline assessment of hydration status and FMD, the subjects completed 100 min of low intensity intermittent walking exercise to achieve hypohydration of -2 % of individual body mass. For the rest of the day, a standardized, low water content diet was provided. The following morning, hydration markers and endothelial function were recorded. RESULTS: Hypohydration by -1.9 +/- 0.1 % of body mass resulted in decreased plasma volume by -3.5 +/- 1.8 % and increased plasma osmolality by 9 +/- 2 mmol kg-1 (P < 0.001). FMD as a response to hypohydration decreased by -26.8 +/- 3.9 % (P < 0.05). CONCLUSION: The data suggested that a small degree of hypohydration induced by moderate exercise and fluid restriction significantly impaired endothelial function. PMID- 26864201 TI - Helicity is the only integral invariant of volume-preserving transformations. AB - We prove that any regular integral invariant of volume-preserving transformations is equivalent to the helicity. Specifically, given a functional I defined on exact divergence-free vector fields of class C(1) on a compact 3-manifold that is associated with a well-behaved integral kernel, we prove that I is invariant under arbitrary volume-preserving diffeomorphisms if and only if it is a function of the helicity. PMID- 26864200 TI - Dynamic secretion during meiotic reentry integrates the function of the oocyte and cumulus cells. AB - The differentiation of the female gamete into a developmentally competent oocyte relies on the protected environment of the ovarian follicle. The oocyte plays a key role in establishing this microenvironment by releasing paracrine factors that control the functions of surrounding somatic cells. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are secreted during follicle growth and play pivotal roles in this local regulation. The current view is that the function of these secreted factors declines in the periovulatory period when the oocyte reenters the meiotic cell cycle. Here, we provide evidence that oocyte reentry into meiosis is instead associated with a shift in the pattern of secretion with a new set of bioactive molecules synthesized before ovulation. Using interleukin 7 (IL7) as a prototypic secreted factor, we show that its secretion is dependent on activation of mRNA translation in synchrony with the cell cycle and that its translation is under the control of somatic cells. IL7 is part of a local feedback loop with the soma because it regulates cumulus cell replication. Similar conclusions are reached when IL7 secretion is measured in human follicular fluid during in vitro fertilization cycles. IL7 concentration in the follicular fluid correlates with the oocyte ability to reach the MII stage of maturation. These findings are consistent with the hypothesis that a new set of local factors is secreted by the oocyte during ovulation. These dynamic secretions are likely critical for promoting the final stages of maturation and oocyte developmental competence. PMID- 26864204 TI - Understanding conductivity in molecular switches: a real space approach in octaphyrins. AB - In recent years, expanded porphyrins have emerged as a promising class of pi conjugated molecules that display unique electronic, optical and conformational properties. Several expanded porphyrins can switch between planar and twisted conformations, which have different photophysical properties. Such a change of topology involves a Huckel-Mobius aromaticity switch in a single molecule and it can be induced by solvent, pH and metallation. These features make expanded porphyrins suitable for the development of a novel type of molecular switches for molecular electronic devices. Octaphyrins consisting of eight pyrrole rings, exhibit twisted-Huckel, Mobius and Huckel pi-conjugation topologies depending on the oxidation and protonation state, with distinct electronic structures and aromaticity. Our working hypothesis is that a significant change in the conductance of expanded porphyrins will be observed after the topology switching. Despite the potential of Huckel-Mobius systems as conductance switches, the relationship between the conductance and the molecular topology is not yet understood. We have explored the performance of local descriptors of conductivity in simple molecules, as well as the relationship with conductance. Since these indexes provide a qualitative measure of delocalization and conductance in the probe molecules, we have carried out a local analysis of electrical conductance changes as a function of the pi-conjugation in two examples. In one of them, the locality of the electronic changes ensures the ability of these indexes to describe the conductance as local. Moreover, it enables to identify which conformational switch would be more efficient from an electronic device perspective. However, we also show that it is not always possible to reduce conductance changes to one bond, and in those molecules where a deep rearrangement occurs far from the structural perturbation, local measures show a limited efficiency. This is a first step for the description of the connection between the molecular structure and conductance in molecular switches. PMID- 26864205 TI - Health Habits of Employees in a Large Medical Center: Time Trends and Impact of a Worksite Wellness Facility. AB - Worksite health interventions are not novel but their effect remains subject of debate. We examined employer-based wellness program to determine health habits trends, and compare prevalence estimates to national data. We conducted serial surveys (1996 and 2007-10) to employees of a large medical center that included questions measuring outcomes, including obesity, regular exercise, cardiovascular activity, and smoking status. Logistic regression models were estimated to compare data by membership across years, considering p-values <= 0.01 as statistically significant. 3,206 employees responded (Response rates 59-68%). Obesity prevalence increased over time in members and nonmembers of the wellness facility, consistent with national trends. Members had a lower prevalence of cigarette smoking compared to nonmembers (overall year-adjusted odds ratio 0.66, P < 0.001). Further, employees had a lower prevalence of cigarette smoking (9.7 vs. 17.3% in 2010, P < 0.001) compared with national data. Wellness facility membership was associated with increased regular exercise and cardiovascular exercise (P < 0.001) compared to nonmembers. In summary, working in a medical center was associated with a decreased prevalence of cigarette smoking, but not with lower prevalence of obesity. Worksite wellness facility membership was associated with increased exercise and decreased cigarette smoking. Employer based interventions may be effective in improving some health behaviors. PMID- 26864206 TI - New Insights on the Impact of Statin Therapy in the Susceptibility to Hypovitaminosis D Through Serum Lipidome Profiling. AB - Hypovitaminosis D is a worldwide clinical problem, affecting populations in numerous ways. Several factors seem to affect vitamin D metabolism, including the suggestion that therapy with the lipid lowering HMG-CoA inhibitors might modulate vitamin D levels. However, the relationship between statins intake and serum levels of vitamin D is still controversial. The present work aimed to add new insights on the association between statins therapy, and more specifically the generation of statins, and the lipid profile in a population of 106 subjects treated with these HMG-CoA inhibitors. Data showed that despite a higher prevalence of hipovitaminosis D in subjects treated with statins, there is no association between statin generation, total and LDL cholesterol and vitamin D levels. Moreover, second generation statins, the most common treatment of hypercholesterolemia in the studied population, promoted the remodelling of serum fatty acids that was characterized by the increase of arachidonic acid (AA) relative levels without affecting eicosapentaenoic acid (EPA) levels. Among statin treated subjects, vitamin D levels did not affect serum fatty acid profile. The statin-related increased ratio AA/EPA suggests a pro- inflammatory status, whose long-term impact should be better clarified in the future. PMID- 26864202 TI - Genomic characterization of sarcomatoid transformation in clear cell renal cell carcinoma. AB - The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 * 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 * 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. PMID- 26864203 TI - Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM. AB - The orchestrated action of genes controls complex biological phenotypes, yet the systematic discovery of gene and drug combinations that modulate these phenotypes in human cells is labor intensive and challenging to scale. Here, we created a platform for the massively parallel screening of barcoded combinatorial gene perturbations in human cells and translated these hits into effective drug combinations. This technology leverages the simplicity of the CRISPR-Cas9 system for multiplexed targeting of specific genomic loci and the versatility of combinatorial genetics en masse (CombiGEM) to rapidly assemble barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing. We applied CombiGEM-CRISPR to create a library of 23,409 barcoded dual guide-RNA (gRNA) combinations and then perform a high-throughput pooled screen to identify gene pairs that inhibited ovarian cancer cell growth when they were targeted. We validated the growth-inhibiting effects of specific gene sets, including epigenetic regulators KDM4C/BRD4 and KDM6B/BRD4, via individual assays with CRISPR-Cas-based knockouts and RNA-interference-based knockdowns. We also tested small-molecule drug pairs directed against our pairwise hits and showed that they exerted synergistic antiproliferative effects against ovarian cancer cells. We envision that the CombiGEM-CRISPR platform will be applicable to a broad range of biological settings and will accelerate the systematic identification of genetic combinations and their translation into novel drug combinations that modulate complex human disease phenotypes. PMID- 26864207 TI - A randomized, 5-arm dose finding study with a mite allergoid SCIT in allergic rhinoconjunctivitis patients. AB - BACKGROUND: The safety and tolerability of a mite allergoid subcutaneous allergen immunotherapy (SCIT) product was previously established. The aim of this study (EudraCT number: 2011-000393-61) was to find the optimally safe and effective allergoid dose by evaluating several dosages in patients with house dust mite (HDM)-induced allergic rhinoconjunctivitis (ARC) using a titrated nasal provocation test (TNPT). METHODS: In total, 290 adult ARC patients (148 females; 142 males) with established HDM allergy and with a positive TNPT were randomized to receive placebo or mite allergoid SCIT 6667, 20 000, 50 000 or 100 000 AUeq/ml for 12 months. Patients were updosed weekly, followed by monthly maintenance dosing. The primary study endpoint comprised the clinical response to TNPT after 12 months of treatment. Secondary endpoints included response to TNPT after 6 months, PNIF measurements, symptom and medication scores during the last 8 weeks of treatment, serum immunoglobulins and safety assessments. RESULTS: After 12 months, a dose-response was observed showing statistically significant improvements in the TNPT with SCIT concentrations of >=20 000 AUeq/ml, while no significantly different outcomes were reached after 6 months. Specific serum IgG and IgG4 levels were dose dependently increased. In the highest dose group, more treatment-emergent adverse events were observed compared with the lower dose groups. CONCLUSION: In this mite allergoid SCIT dose finding study in HDM-induced ARC, concentrations of >=20 000 AUeq/ml showed both immunological effects and clinical efficacy in the TNPT compared with placebo. The risk-benefit ratio favours 20 000 AUeq/ml and 50 000 AUeq/ml strengths for further clinical development. PMID- 26864208 TI - Digital Sorting of Pure Cell Populations Enables Unambiguous Genetic Analysis of Heterogeneous Formalin-Fixed Paraffin-Embedded Tumors by Next Generation Sequencing. AB - Precision medicine in oncology requires an accurate characterization of a tumor molecular profile for patient stratification. Though targeted deep sequencing is an effective tool to detect the presence of somatic sequence variants, a significant number of patient specimens do not meet the requirements needed for routine clinical application. Analysis is hindered by contamination of normal cells and inherent tumor heterogeneity, compounded with challenges of dealing with minute amounts of tissue and DNA damages common in formalin-fixed paraffin embedded (FFPE) specimens. Here we present an innovative workflow using DEPArrayTM system, a microchip-based digital sorter to achieve 100%-pure, homogenous subpopulations of cells from FFPE samples. Cells are distinguished by fluorescently labeled antibodies and DNA content. The ability to address tumor heterogeneity enables unambiguous determination of true-positive sequence variants, loss-of-heterozygosity as well as copy number variants. The proposed strategy overcomes the inherent trade-offs made between sensitivity and specificity in detecting genetic variants from a mixed population, thus rescuing for analysis even the smaller clinical samples with low tumor cellularity. PMID- 26864209 TI - A chloroplast-localized protein LESION AND LAMINA BENDING affects defence and growth responses in rice. AB - Understanding how plants allocate their resources to growth or defence is of long term importance to the development of new and improved varieties of different crops. Using molecular genetics, plant physiology, hormone analysis and Next Generation Sequencing (NGS)-based transcript profiling, we have isolated and characterized the rice (Oryza sativa) LESION AND LAMINA BENDING (LLB) gene that encodes a chloroplast-targeted putative leucine carboxyl methyltransferase. Loss of LLB function results in reduced growth and yield, hypersensitive response (HR) like lesions, accumulation of the antimicrobial compounds momilactones and phytocassanes, and constitutive expression of pathogenesis-related genes. Consistent with these defence-associated responses, llb shows enhanced resistance to rice blast (Magnaporthe oryzae) and bacterial blight (Xanthomonas oryzae pv. oryzae). The lesion and resistance phenotypes are likely to be caused by the over accumulation of jasmonates (JAs) in the llb mutant including the JA precursor 12 oxo-phytodienoic acid. Additionally, llb shows an increased lamina inclination and enhanced early seedling growth due to elevated brassinosteroid (BR) synthesis and/or signalling. These findings show that LLB functions in the chloroplast to either directly or indirectly repress both JA- and BR-mediated responses, revealing a possible mechanism for controlling how plants allocate resources for defence and growth. PMID- 26864212 TI - Unveiling the "Three-Finger Pharmacophore" Required for p53-MDM2 Inhibition by Saturation-Transfer Difference (STD) NMR Initial Growth-Rates Approach. AB - Inhibitors of the p53-MDM2 protein-protein interaction are emerging as a new and validated approach to treating cancer. Herein, we describe the synthesis and inhibitory evaluation of a series of isoquinolin-1-one analogues, and highlight the utility of an initial growth-rates saturation-transfer difference (STD) NMR approach supported by protein-ligand docking to investigate p53-MDM2 inhibition. The approach is illustrated by the study of compound 1, providing key insights into the binding mode of this kind of MDM2 ligands and, more importantly, readily unveiling the previously proposed three-finger pharmacophore requirement for p53 MDM2 inhibition. PMID- 26864210 TI - A Phase I Clinical, Pharmacokinetic, and Pharmacodynamic Study of Weekly or Every Three Week Ixabepilone and Daily Sunitinib in Patients with Advanced Solid Tumors. AB - PURPOSE: To evaluate the safety, MTD, pharmacokinetics/pharmacodynamics, and early clinical activity of ixabepilone given either weekly or every 3 weeks in combination with daily sunitinib in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Eligible patients received either weekly (schedule A) or every 3 weeks (schedule B) ixabepilone at escalating doses (schedule A: 7.5, 15, or 20 mg/m(2); schedule B: 20, 30, or 40 mg/m(2)), and oral sunitinib (37.5 mg daily), starting on day 8 of cycle 1. Dose-limiting toxicities (DLT) were assessed during cycle 1. RESULTS: The ixabepilone and sunitinib combination was fairly well tolerated. DLTs were observed in 3 subjects (1 in schedule 3A and 2 in schedule 3B). The most common grade 3-4 hematologic and nonhematologic adverse events were leukopenia and fatigue, respectively. Four patients (3 in schedule A) achieved a partial response, while 13 patients had stable disease. Nine of 17 heavily pretreated colorectal cancer patients had clinical benefit. Coadministration of sunitinib with ixabepilone on a weekly (but not every 3 week) schedule was associated with a significant increase in the half-life and a significant decrease in the clearance of ixabepilone. Correlative studies demonstrated a significant association between higher baseline plasma angiogenic activity (PAA) and clinical benefit in schedule A patients. Weekly, but not every 3 weeks, ixabepilone led to a significant decrease in PAA postbaseline. CONCLUSIONS: Coadministration of ixabepilone with sunitinib has acceptable toxicity and encouraging clinical activity in heavily pretreated patients, particularly in patients with metastatic colorectal cancer. Clin Cancer Res; 22(13); 3209-17. (c)2016 AACR. PMID- 26864211 TI - CD44+ Cells in Head and Neck Squamous Cell Carcinoma Suppress T-Cell-Mediated Immunity by Selective Constitutive and Inducible Expression of PD-L1. AB - PURPOSE: Human tumors consist of heterogeneous populations of cells with distinct marker expression and functional properties. In squamous cell carcinoma of the head and neck (SCCHN), CD44 is a well-characterized marker of a resilient subpopulation of cells associated with increased tumorigenesis, radioresistance, and chemoresistance. Evidence indicates that these cells have an immunosuppressive phenotype; however, mechanisms have been elusive. EXPERIMENTAL DESIGN: Using primary human SCCHN tumor samples and patient-derived xenografts, we examined the phenotypes of subsets of tumor cells and investigated mechanisms regulating their immunogenicity. RESULTS: CD44(+) cells in primary human SCCHN were found to have an epithelial-to-mesenchymal (EMT) phenotype and were less immunogenic than CD44(-) cells when cultured with autologous CD8(+) tumor infiltrating T cells. Selective expression of the programmed death-ligand 1 (PD L1) was observed on CD44(+) cells compared with CD44(-) cells and was associated with constitutive phosphorylation of STAT3 on CD44(+) cells. Importantly, inhibition of STAT3 decreased expression of PD-L1 on CD44(+) cells. IFNgamma treatment preferentially induced even further PD-L1 expression on CD44(+) cells and was associated with enhanced IFNgamma receptor expression and phosphorylation of STAT1. Finally, the decreased immunogenicity of CD44(+) cells was partially reversed by antibody blockade of the programmed death 1 (PD-1) receptor, indicating that the differences in PD-L1 expression between CD44(+) and CD44(-) cells are biologically and clinically relevant. CONCLUSIONS: Our findings provide a mechanism by which long-lived CD44(+) tumor-initiating cells can selectively evade host immune responses and provide rationale for targeting the PD-1 pathway in the adjuvant therapy setting of SCCHN. Clin Cancer Res; 22(14); 3571-81. (c)2016 AACR. PMID- 26864215 TI - The effects of advanced age on primary total knee arthroplasty: a meta-analysis and systematic review. AB - BACKGROUND: Total knee arthroplasty is an effective treatment when nonsurgical treatments fail, but it is associated with risk of complications which may be increased in advanced age. The purpose of this study was to quantify age-related differences in perioperative morbidity and mortality after total knee arthroplasty through systematic review of existing literature. METHODS: PubMed, the Cochrane database of systematic reviews, Scopus, and clinicaltrials.gov, were queried for relevant studies that compared primary total knee arthroplasty outcomes of mortality, myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE) and functional status, of geriatric patients (>75 years old) with a younger control group (<65 years old). Pertinent journals and reference lists were hand searched. Eligibility criteria included all articles except case reports, meta-analyses, and systematic reviews. Two authors independently extracted data from each paper. Article quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Twenty-two studies were included. Geriatric patients had higher rates of mortality, MI, DVT, and length of stay in older compared to younger patients, however the absolute magnitude of these increases were small. The increase in mortality may have reflected decreased life expectancy in the geriatric populations as opposed to mortality specifically due perioperative risk. There were no differences in PE incidence and improvement in pain and functional status was equal in older and younger patients. Existing studies were limited by non-randomized patient selection, as well as variation in definitions and methodology. CONCLUSIONS: Existing data supports offering primary total knee arthroplasty to select geriatric patients, although the risk of complications may be increased. Much of the data was of poor quality. Future prospective studies are needed to better identify risks and benefits of total knee arthroplasty so that patients and surgeons can make informed decisions. PMID- 26864216 TI - Characterization of a newly isolated strain Pseudomonas sp. C27 for sulfide oxidation: Reaction kinetics and stoichiometry. AB - Sulfide biooxidation by the novel sulfide-oxidizing bacteria Pseudomonas sp. C27, which could perform autotrophic and heterotrophic denitrification in mixotrophic medium, was studied in batch and continuous systems. Pseudomonas sp. C27 was able to oxidize sulfide at concentrations as high as 17.66 mM. Sulfide biooxidation occurred in two distinct stages, one resulting in the formation of sulfur with nitrate reduction to nitrite, followed by thiosulfate formation with nitrite reduction to N2. The composition of end-products was greatly impacted by the ratio of sulfide to nitrate initial concentrations. At a ratio of 0.23, thiosulfate represented 100% of the reaction products, while only 30% with a ratio of 1.17. In the continuous bioreactor, complete removal of sulfide was observed at sulfide concentration as high as 9.38 mM. Overall sulfide removal efficiency decreased continuously upon further increases in influent sulfide concentrations. Based on the experimental data kinetic parameter values were determined. The value of maximum specific growth rate, half saturation constant, decay coefficient, maintenance coefficient and yield were to be 0.11 h(-1), 0.68 mM sulfide, 0.11 h(-1), 0.21 mg sulfide/mg biomass h and 0.43 mg biomass/mg sulfide, respectively, which were close to or comparable with those reported in literature by other researches. PMID- 26864218 TI - Synthesis and Applications of Silyl 2-Methylprop-2-ene-1-sulfinates in Preparative Silylation and GC-Derivatization Reactions of Polyols and Carbohydrates. AB - Trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, and triisopropylsilyl 2 methylprop-2-ene-1-sulfinates were prepared through (CuOTf)2?C6H6-catalyzed sila ene reactions of the corresponding methallylsilanes with SO2 at 50 degrees C. Sterically hindered, epimerizable, and base-sensitive alcohols gave the corresponding silyl ethers in high yields and purities at room temperature and under neutral conditions. As the byproducts of the silylation reaction (SO2 +isobutylene) are volatile, the workup was simplified to solvent evaporation. The developed method can be employed for the chemo- and regioselective semiprotection of polyols and glycosides and for the silylation of unstable aldols. The high reactivity of the developed reagents is shown by the synthesis of sterically hindered per-O-tert-butyldimethylsilyl-alpha-D-glucopyranose, the X-ray crystallographic analysis of which is the first for a per-O-silylated hexopyranose. The per-O-silylation of polyols, hydroxy carboxylic acids, and carbohydrates with trimethylsilyl 2-methylprop-2-ene-1-sulfinate was coupled with the GC analysis of nonvolatile polyhydroxy compounds both qualitatively and quantitatively. PMID- 26864219 TI - Which diagnostic findings in disorders with excessive daytime sleepiness are really helpful? A retrospective study. AB - Due to extensive clinical and electrophysiological overlaps, the correct diagnosis of disorders with excessive daytime sleepiness is often challenging. The aim of this study was to provide diagnostic measures that help discriminating such disorders, and to identify parameters, which don't. In this single-center study, we retrospectively identified consecutive treatment-naive patients who suffered from excessive daytime sleepiness, and analyzed clinical and electrophysiological measures in those patients in whom a doubtless final diagnosis could be made. Of 588 patients, 287 reported subjective excessive daytime sleepiness. Obstructive sleep apnea is the only disorder that could be identified by polysomnography alone. The diagnosis of insufficient sleep syndrome relies on actigraphy as patients underestimate their sleep need and the disorder shares several clinical and electrophysiological properties with both narcolepsy type 1 and idiopathic hypersomnia. Sleep stage sequencing on MSLT appears helpful to discriminate between insufficient sleep syndrome and narcolepsy. Sleep inertia is a strong indicator for idiopathic hypersomnia. There are no distinctive electrophysiological findings for the diagnosis of restless legs syndrome. Altogether, EDS disorders are common in neurological sleep laboratories, but usually cannot be diagnosed based on PSG and MSLT findings alone. The diagnostic value of actigraphy recordings can hardly be overestimated. PMID- 26864221 TI - [Editorial]. PMID- 26864222 TI - [Violent crime by youth and adolescents]. PMID- 26864223 TI - [Suicide and suicide tendencies in adolescent detainees]. AB - Following accidents, suicide is the second leading cause of death in adolescence. This stage of life has the most suicide attempts of all age groups. In addition to mentally ill juveniles, adolescent delinquents represent a high-risk group for suicidal behavior and completed suicide. In particular, the population of detainees, an extreme form of juvenile delinquency, have a 16- to 18-fold higher risk of suicidal behavior and suicide compared to the general population. Because the composition of juvenile detainees differs greatly from that of detained adults, age-specific scientific approaches and prevention programs are needed. This task cannot be addressed by juvenile detention staff alone, but rather demands close cooperation between adolescent psychiatrists, psychologists, prison medical staff, legal experts and prison officers to use the opportunity for suicide prevention in juvenile detention facilities. PMID- 26864220 TI - Genome-guided Investigation of Antibiotic Substances produced by Allosalinactinospora lopnorensis CA15-2(T) from Lop Nor region, China. AB - Microbial secondary metabolites are valuable resources for novel drug discovery. In particular, actinomycetes expressed a range of antibiotics against a spectrum of bacteria. In genus level, strain Allosalinactinospora lopnorensis CA15-2(T) is the first new actinomycete isolated from the Lop Nor region, China. Antimicrobial assays revealed that the strain could inhibit the growth of certain types of bacteria, including Acinetobacter baumannii and Staphylococcus aureus, highlighting its clinical significance. Here we report the 5,894,259 base pairs genome of the strain, containing 5,662 predicted genes, and 832 of them cannot be detected by sequence similarity-based methods, suggesting the new species may carry a novel gene pool. Furthermore, our genome-mining investigation reveals that A. lopnorensis CA15-2(T) contains 17 gene clusters coding for known or novel secondary metabolites. Meanwhile, at least six secondary metabolites were disclosed from ethyl acetate (EA) extract of the fermentation broth of the strain by high-resolution UPLC-MS. Compared with reported clusters of other species, many new genes were found in clusters, and the physical chromosomal location and order of genes in the clusters are distinct. This study presents evidence in support of A. lopnorensis CA15-2(T) as a potent natural products source for drug discovery. PMID- 26864224 TI - [Power to the children? - Machiavellianism in children and adolescents]. AB - The desire for power and social dominance plays a significant role in the development of social aggression. Although the construct of Machiavellianism reflects these aspects well, it has hardly been recognized in Germany. In this review article the construct of Machiavellianism will be presented. Previous research on the relationship between Machiavellianism and particularly aggressive behavior in children and adolescents are critically discussed and implications for future studies are derived. PMID- 26864225 TI - ["Tit for Tat?" The development of prosocial behavior and its relationship to externalizing and internalizing problems]. AB - Supporting other human beings is a fundamental aspect of human societies. Such so called prosocial behavior is expressed in helping others, cooperating and sharing with them. This article gives an overview both of the development of prosocial behavior across childhood and of the relationship between prosociality and externalizing and internalizing problems. Especially externalizing problems are negatively associated with prosocial behavior, whereas the relationships with prosocial behavior are more heterogeneous for internalizing problems. Studies investigating developmental trajectories demonstrate that prosocial behavior and externalizing problems are not opposite ends of a continuum. Rather, they are two independent dimensions that may also co-occur in development. The same applies to internalizing problems, which can co-occur with pronounced prosociality as well as with low prosociality. PMID- 26864226 TI - [Placement of children and adolescents following seclusion and restraint actions a study on family-court approvals of minors in youth welfare, child and adolescent psychiatry and jail according to Para. 1631 German Civil Code]. AB - According to German law (Para. 1631b German Civil Code), the placement of children and adolescents following seclusion and restraint actions must be approved by a family court. We analyzed the family court data of a court district in Berlin (Tempelhof-Kreuzberg) concerning cases of "placement of minors" between 2008 and 2011. A total of 474 such procedures were discovered. After data clearing and correction of cases (e. g., because of emergency interventions of the youth welfare system taking children into custody according to Para. 42, German Civil Code VIII), 376 cases remained. Of these 376 procedures in the years 2008 to 2011, 127 cases concerned children and adolescents according to Para. 1631b German Civil Code, and 249 procedures were settled either by dismissal, withdrawal or by repealing the initial decision to place the child with restrain or seclusion by means of an interim order or by filing an appeal against the final decision. Of the 127 procedures, 68 concerned girls, who were on average slightly younger than boys (14.5 years vs. 15.1 years). In two thirds of the procedures, the children and adolescents were German citizens. The majority of youths involved were living at home at the time of the procedure, but in 15 % of the case the youths were homeless. Most of the adolescents were treated with restraint in child and adolescent psychiatry. The most frequently quoted reasons for seclusion were substance abuse, suicide risk and running away from home/being homeless. PMID- 26864227 TI - [Psychiatric disorders in children and adolescents in family law proceedings. Empirical analyses from psychological expert assessment]. AB - Objective: This study examined the frequency and distribution of mental health problems in children and adolescents who had previously been psychologically evaluated in family law proceedings. Method: The data stem from psychological evaluations (N=298) conducted between 2008 and 2012 at an evaluation institute in Bremen, Germany. The reports included were analyzed for indications of mental health problems by means of a content analysis. The total sample consisted of 496 children and adolescents. Results: At least one mental health problem (according to ICD-F) was found in 39.5% of the children and adolescents. The comorbidity rate was 38.7%. Developmental deficits appeared in 12.3%, emotional or conduct problems in 22.8% of the sample. Furthermore, 11.5% were reported as having been victims of violence. Frequency distributions of mental health problems with respect to the juridical issues in question are given. Conclusions: These results provide a first empirical overview of mental health problems in psychologically evaluated children and adolescents. Our findings highlight the need for future studies to further examine mental health problems of children and adolescents in family court proceedings with respect to the juridical issues in question. PMID- 26864228 TI - [Psychosocial disadvantages in incarcerated girls and boys]. AB - OBJECTIVE: Longitudinal studies found that criminal behavior in juveniles often concurs with neighborhood disadvantage and family dysfunction, especially in girls. In this study we assessed the psychosocial background in incarcerated juveniles and analyzed the data for each gender separately. METHOD: The Multidimensional Clinical Screening Inventory for delinquent juveniles (MCSI) was used to assess school history, psychiatric history, family background, abuse and neglect and motive for crime. The sample consisted of 294 juveniles (46 females and 248 males). RESULTS: Innerfamilial abuse/neglect was reported by 91% (girls) and 79% (boys). 76% (girls) and 88% (boys) reported school-problems. 57% (girls) and 29% (boys) reported to have recieved psychiatric pretreatment. In girls we found significantly higher prevalence rates for parental divorce, incarceration of mother, abuse/neglect and psychiatric pretreatment. Significantly more girls reported a co-occurrence of school-problems and experiences of separation and loss and abuse (65.2% vs. 46.4%, chi2=5.51, df=1, p<.05). CONCLUSION: Incarcerated juveniles, especially females, are and have been exposed to multiple psychosocial burdens. Therefore it is necessary to implement prevention programs for psychosocially stressed families. Forensic intervention in and after detention has to include a family centered approach. PMID- 26864229 TI - [Reports. Joint statement by the Societies of Child and Adolescent Psychiatry and the professional associations DGKJP, BAG KJPP, BKJPP]. PMID- 26864234 TI - The future of iPS cells in advancing regenerative medicine. AB - Induced pluripotent stem (iPS) cells have great potential in regenerative medicine, including cell replacement therapies and disease modelling in vitro. However, with this potential comes several challenges, including clinical safety, reprogramming and differentiation efficiency, and compromised functionality of differentiated cell types after transplantation. Many of these issues arise from imprecise control of cell fate. With large-scale sequencing and genome-editing technologies we can now precisely manipulate the genome, which has expanded our knowledge of functional cell types and cell identity. These technologies may improve our efforts in generating iPS-derived therapeutic cells and in development of therapies for human diseases. PMID- 26864235 TI - Continuous positive airway pressure (CPAP) to treat respiratory distress in newborns in low- and middle-income countries. AB - Severe respiratory distress is a serious complication common to the three major causes of neonatal mortality and morbidity (prematurity, intra-partum-related hypoxia and infections). In low- and middle-income countries (LMICs), 20% of babies presenting with severe respiratory distress die.Continuous positive airway pressure (CPAP), is an effective intervention for respiratory distress in newborns and widely used in high-income countries. Following the development of simple, safe and relatively inexpensive CPAP devices, there is potential for large-scale implementation in the developing world.In this article, we describe existing CPAP systems and present a review of the current literature examining the effectiveness of CPAP compared to standard care (oxygen) in newborns with respiratory distress. We also discuss the evidence gap which needs to be addressed prior to its integration into health systems in LMICs. PMID- 26864237 TI - Horizontal mucosal thickness at implant sites as it correlates with the integrity and thickness of the buccal bone plate. AB - OBJECTIVES: To histologically assess the association between the horizontal mucosal thickness (MT) at implant sites with the integrity and thickness of the buccal bone plate in a canine model. MATERIALS AND METHODS: Two-piece titanium implants were placed at chronic-type lateral ridge defects. The resulting vestibular dehiscence-type defects (vertical dimensions of 2-8 mm) were left untreated. After a submerged healing period of 2 and 8 weeks (n = 6 fox hounds each), dissected blocks were processed for histomorphometrical analyses [e.g. MT, bone thickness (BT) and residual defect length]. RESULTS: Linear regression revealed significant associations between vestibular MT and BT values after 2 (R2 = 0.22, B = -0.37, P < 0.0001) and 8 weeks (R2 = 0.37, B = -0.45, P < 0.001) of healing. CONCLUSION: The present analysis has pointed to an inverse relationship between horizontal MT and BT values at the vestibular aspect of submerged titanium implants. MT was most pronounced in the absence of a buccal bone plate. PMID- 26864238 TI - Histologic Examination of an Assemblage of Psittacosaurus (Dinosauria: Ceratopsia) Juveniles From the Yixian Formation (Liaoning, China). AB - Psittacosaurus is one of the most abundant dinosaurs known, which allows for extensive study of its growth and form. Previous studies have evaluated growth trajectories of Psittacosaurus using bone histology. However, we present the first study of Psittacosaurus comparative juvenile histology and describe the histology of Psittacosaurus within its first year of life based on multiple sections taken from an exquisite monospecific assemblage of juveniles from the Yixian Formation in Liaoning, China. Specimens studied had femur lengths ranging from 30 to 36 mm. The five juveniles examined all have similar histologic patterns in the midshaft and epiphyseal regions showing that there is limited plasticity in bone development in juvenile Psittacosaurus and that all of the specimens in the assemblage were likely the same age. The microstructure patterns are compatible with the hypothesis that Psittacosaurus was precocial and that these juveniles were neonates. Based on comparisons with other juvenile ornithischians, juvenile Psittacosaurus had a growth rate similar to Orodromeus, slower than that of Maiasaura, Dysalotosaurus, or hadrosaurs consistent with small body size. Our results support previous studies that demonstrated that the orientation of vascular canals is likely not solely reflective of growth rate, but is also affected by underlying biomechanical, structural processes. The number of studies done on theropod and sauropodomorph histology dwarfs those of ornithischians. More studies of ornithischian histology are necessary in order to better establish phylogenetic trends in microstructure and to learn more about growth in this important clade. PMID- 26864236 TI - Skin collagen fluorophore LW-1 versus skin fluorescence as markers for the long term progression of subclinical macrovascular disease in type 1 diabetes. AB - BACKGROUND: Skin collagen Long Wavelength Fluorescence (LWF) is widely used as a surrogate marker for accumulation of advanced glycation end-products. Here we determined the relationship of LWF with glycemia, skin fluorescence, and the progression of complications during EDIC in 216 participants from the DCCT. METHODS: LW-1 and collagen-linked fluorescence (CLF) were measured by either High Performance Liquid Chromatography (HPLC) with fluorescence detection (LW-1) or total fluorescence of collagenase digests (CLF) in insoluble skin collagen extracted from skin biopsies obtained at the end of the DCCT (1993). Skin intrinsic fluorescence (SIF) was noninvasively measured on volar forearm skin at EDIC year 16 by the SCOUT DS instrument. RESULTS: LW-1 levels significantly increased with age and diabetes duration (P < 0.0001) and significantly decreased by intensive vs. conventional glycemic therapy in both the primary (P < 0.0001) and secondary (P < 0.037) DCCT cohorts. Levels were associated with 13-16 year progression risk of retinopathy (>3 sustained microaneurysms, P = 0.0004) and albumin excretion rate (P = 0.0038), the latter despite adjustment for HbA1c. Comparative analysis for all three fluorescent measures for future risk of subclinical macrovascular disease revealed the following significant (P < 0.05) associations after adjusting for age, diabetes duration and HbA1c: coronary artery calcium with SIF and CLF; intima-media thickness with SIF and LW-1; and left ventricular mass with LW-1 and CLF. CONCLUSIONS: LW-1 is a novel risk marker that is robustly and independently associated with the future progression of microvascular disease, intima-media thickness and left ventricular mass in type 1 diabetes. Trial registration NCT00360815 and NCT00360893 at clinicaltrials.gov. PMID- 26864239 TI - Message on a bottle: are alcohol warning labels about cancer appropriate? AB - BACKGROUND: Although most Australians are unaware of the risk, there is strong evidence for a direct link between alcohol consumption and many types of cancer. Warning labels on alcohol products have been proposed as a cost-effective strategy to inform the community of this health risk. We aimed to identify how Australians might respond to such an approach. METHODS: We conducted a national online survey canvassing responses to four separate cancer warning messages on labels. The graphically presented messages were informed by qualitative data from a series of focus groups among self-identified 'light-to-moderate' drinkers. For each label, participants were asked their level of agreement with impact statements about raising awareness, prompting conversation, influencing drinking behaviour and educating others about cancer risk. We analysed responses according to demographic and other factors, including self-reported drinking behaviour (using the 3-item Alcohol Use Disorder Test - AUDIT-C - scores). RESULTS: Approximately 1600 participants completed the survey, which was open to all Australian adults over a period of 1 month in 2014. Overall, the labels were well received, with the majority (>70 %) agreeing all labels could raise awareness and prompt conversations about the cancer risk associated with alcohol. Around 50 % or less agreed that the labels could influence drinking behaviour, but larger proportions agreed that the labels would prompt them to discuss the issue with family and friends. Although sex, AUDIT-C score and age were significantly associated with agreement on bivariate analysis, multivariate analyses demonstrated that being inclined to act upon warning label recommendations in general was the most important predictor of agreement with all of the impact statements. Having a low AUDIT-C score also predicted agreement that the labels might prompt behaviour change in friends. CONCLUSIONS: The findings suggest that providing detailed warnings about cancer risk on alcohol products is a viable means of increasing public awareness of the health risks associated with alcohol consumption. Further research is needed to explore the ability of such warnings to influence behavioural intentions and actual drinking behaviour. PMID- 26864240 TI - A case report on allopurinol induced crystalline maculopathy. PMID- 26864241 TI - Decreased exposure of atorvastatin in diabetic rats partly due to induction of hepatic Cyp3a and Oatp2. AB - 1. Atorvastatin is frequently prescribed for lowering blood cholesterol and for prevention of events associated with cardiovascular disease. The aim of this study was to investigate the pharmacokinetics of atorvastatin in diabetic rats. 2. Diabetes was induced in rats by combination of high-fat diet and low-dose streptozotocin (35 mg/kg). Plasma concentrations of atorvastatin following oral (10 mg/kg) and intravenous (2 mg/kg) administrations to rats were measured by LC MS. Metabolism and uptake of atorvastatin in primary hepatocytes of experimental rats were assessed. Protein expressions and activities of hepatic Cyp3a and Oatp2 were further investigated. 3. Clearances of atorvastatin in diabetic rats following oral and intravenous administrations were remarkably increased, leading to marked decreases in area-under-the-plasma concentration-time curve (AUC). The estimated oral and systematic clearances of atorvastatin in diabetic rats were 4.5-fold and 2.0-fold of control rats, respectively. Metabolism and uptake of atorvastatin in primary hepatocytes isolated from diabetic rats were significantly increased, which were consistent with the up-regulated protein expressions and activities of hepatic Cyp3a and Oatp2. 4. All these results demonstrated that the plasma exposure of atorvastatin was significantly decreased in diabetic rats, which was partly due to the up-regulated activities and expressions of both hepatic Cyp3a and Oatp2. PMID- 26864242 TI - Resuscitation is futile in terminally ill patients. PMID- 26864243 TI - AN ODORANT-BINDING PROTEIN INVOLVED IN PERCEPTION OF HOST PLANT ODORANTS IN LOCUST Locusta migratoria. AB - Locusts, Locusta migratoria (Orthoptera: Acrididae), are extremely destructive agricultural pests, but very little is known of their molecular aspects of perception to host plant odorants including related odorant-binding proteins (OBPs), though several OBPs have been identified in locust. To elucidate the function of LmigOBP1, the first OBP identified from locust, RNA interference was employed in this study to silence LmigOBP1, which was achieved by injection of dsRNA targeting LmigOBP1 into the hemolymph of male nymphs. Compared with LmigOBP1 normal nymphs, LmigOBP1 knockdown nymphs significantly decreased food (maize leaf, Zea mays) consumption and electro-antennography responses to five maize leaf volatiles, ((Z)-3-hexenol, linalool, nonanal, decanal, and (Z)-3 hexenyl acetate). These suggest that LmigOBP1 is involved in perception of host plant odorants. PMID- 26864244 TI - An information-theoretic approach for the evaluation of surrogate endpoints based on causal inference. AB - In this work a new metric of surrogacy, the so-called individual causal association (ICA), is introduced using information-theoretic concepts and a causal inference model for a binary surrogate and true endpoint. The ICA has a simple and appealing interpretation in terms of uncertainty reduction and, in some scenarios, it seems to provide a more coherent assessment of the validity of a surrogate than existing measures. The identifiability issues are tackled using a two-step procedure. In the first step, the region of the parametric space of the distribution of the potential outcomes, compatible with the data at hand, is geometrically characterized. Further, in a second step, a Monte Carlo approach is proposed to study the behavior of the ICA on the previous region. The method is illustrated using data from the Collaborative Initial Glaucoma Treatment Study. A newly developed and user-friendly R package Surrogate is provided to carry out the evaluation exercise. PMID- 26864245 TI - Determination of Labeled Fatty Acids Content in Milk Products, Infant Formula, and Adult/Pediatric Nutritional Formula by Capillary Gas Chromatography: Collaborative Study, Final Action 2012.13. AB - A collaborative study was conducted on AOAC First Action Method 2012.13 "Determination of Labeled Fatty Acids Content in Milk Products and Infant Formula by Capillary Gas Chromatography," which is based on an initial International Organization for Standardization (ISO)-International Dairy Federation (IDF) New Work Item that has been moved forward to ISO 16958:2015|IDF 231:2015 in November 2015. It was decided to merge the two activities after the agreement signed between ISO and AOAC in June 2012 to develop common standards and to avoid duplicate work. The collaborative study was performed after having provided highly satisfactory single-laboratory validation results [Golay, P.A., & Dong, Y. (2015) J. AOAC Int. 98, 1679-1696] that exceeded the performance criteria defined in AOAC Standard Method Performance Requirement (SMPR((r))) 2012.011 (September 29, 2012) on 12 products selected by the AOAC Stakeholder Panel on Infant Formula (SPIFAN). After a qualification period of 1 month, 18 laboratories participated in the fatty acids analysis of 12 different samples in duplicate. Six samples were selected to meet AOAC SPIFAN requirements (i.e., infant formula and adult nutritionals in powder and liquid formats), and the other Six samples were selected to meet ISO-IDF requirements (i.e., dairy products such as milk powder, liquid milk, cream, butter, infant formula with milk, and cheese). The fatty acids were analyzed directly in all samples without preliminary fat extraction, except in one sample (cheese). Powdered samples were analyzed after dissolution (i.e., reconstitution) in water, whereas liquid samples (or extracted fat) were analyzed directly. After addition of the internal standards solution [C11:0 fatty acid methyl ester (FAME) and C13:0 triacylglycerols (TAG)] to the samples, fatty acids attached to lipids were transformed into FAMEs by direct transesterification using methanolic sodium methoxide. FAMEs were separated using highly polar capillary GLC and were identified by comparison with the retention times of pure analytical standards. Quantification of fatty acids was done relative to C11:0 FAME as internal standard and to instrument response factors (determined separately using calibration standards mixture). The performance of the method (i.e., transesterification) was monitored in all samples using the second internal standard, C13:0 TAG. RSDR values were summarized separately for labeled fatty acids in SPIFAN materials and ISO-IDF materials due to different expression of results. This method was applied to representative dairy, infant formula, and adult/pediatric nutritional products and demonstrated global acceptable reproducibility precision for all fatty acids analyzed (i.e., 46 individuals and/or groups) for these categories of products. PMID- 26864246 TI - Response to: 'A dose-response relationship between severity of disc degeneration and intervertebral disc height in the lumbosacral spine'-authors' reply. PMID- 26864247 TI - Improved analyses of single cases: Dynamic multilevel analysis. AB - This project identifies some difficulties when analyzing single-case data and showcases a new method, dynamic multilevel analysis (DMA). We re-analyze a published, meta-analysis of single-case interventions for participants with autism. Analytic difficulties include missing data, nested data, baseline trends, time periods, recency effects, many hypotheses' false positives, interactions among explanatory variables, indirect effects (including false negatives), and sampling errors. Furthermore, non-overlapping analyses can yield contested results, overvalue data near overlap boundaries, lose statistical power, and lack estimates of explained variance or unexplained residuals. To address these difficulties, DMA integrates several methods, including multilevel and time series analyses. DMA re-analysis not only showed robust intervention effects, but also time-, outcome-, and intervention component-specific effects. Moreover, DMA informs the suitability of time hypotheses or meta-analysis, and DMA's components can be used separately, notably its time-series analyses for small samples (e.g., one participant). Hence, DMA can help researchers analyze single-case data more accurately. PMID- 26864248 TI - Usual interstitial pneumonia in asbestos-exposed cohorts - concurrent idiopathic pulmonary fibrosis or atypical asbestosis? AB - AIMS: To determine whether usual interstitial pneumonia (UIP) pattern fibrosis is seen in asbestosis. METHODS AND RESULTS: The occurrence of UIP pattern fibrosis was studied in four asbestos cohorts systematically referred following postmortem to the UK Pneumoconiosis Unit, Cardiff. The combined exposed workforce comprised >25 000 persons. Over the 17-year period, 233 subjects were identified; 210 had degrees of interstitial fibrosis with a fibrotic non-specific interstitial pneumonia pattern and subpleural accentuation, and three showed UIP pattern fibrosis. All three of these cases showed grade 4 fibrosis (honeycombing) with no asbestos fibre dose-response correlation. A Poisson distribution of probability analysis indicated that the observed cases of UIP in this workforce could be wholly accounted for by the prevalence of idiopathic pulmonary fibrosis (IPF) in the population. CONCLUSIONS: UIP pattern fibrosis is rarely observed in asbestos exposed subjects, and shows no dose-response correlation with asbestos fibres on mineral analysis; this points to an alternative disease, such as IPF. The results indicate that UIP pattern fibrosis should not be regarded as genuine asbestosis, irrespective of the status of asbestos biomarkers, and this impacts upon the postmortem handling of asbestos-related deaths. PMID- 26864249 TI - An Electroactive, Tunable, and Frequency Selective Surface Utilizing Highly Stretchable Dielectric Elastomer Actuators Based on Functionally Antagonistic Aperture Control. AB - An active, frequency selective surface utilizing a silver-nanowire-coated dielectric elastomer with a butterfly-shaped aperture pattern is realized by properly exploiting the electroactive control of two antagonistic functions (stretching vs compression) on a patterned dielectric elastomer actuator. PMID- 26864251 TI - High cystatin C levels predict undesirable outcome for diabetic foot ulcerations. AB - We investigated the relationship between serum cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). A population-based cohort study involving 1018 patients with type 2 diabetes was conducted. These patients recruited and divided into two groups: nondiabetic foot ulcer group (NDF, n = 865, 85.5%) and diabetic foot ulcer group (DFU, n = 147, 14.5%).After a 1-year follow-up, DFUs were grouped into healing (n = 110, 74.8%) and nonhealing (n = 37, 25.2%) group based on the clinical prognosis. Compared with the healing group, the nonhealing group were older, had long diabetic duration and had significantly increased serum cystatin C concentrations in DFU (p < 0.01). After adjustments for age, diabetes duration, renal function and infection control, multiple logistical regression analysis revealed that cystatin C remained associated increased risk of undesirable DFU outcome (OR = 7.279, 95% CI: 1.299 40.784, p < 0.05). When divided into quartiles according to cystatin C levels, the healing rate of Quartile 4 was significantly lower (57.9%) compared with other groups (p < 0.01). The odd is ratio (OR) analysis showed that the risk of undesirable DFU outcome in Quartile 4 was significantly higher (OR = 4.554, 95% CI: 3.14-5.12, p < 0.05) compared with that in Quartile 1. We concluded that there was a strong and independent association between serum cystatin C and diabetic foot ulceration prognosis, cystatin C > 1.35 mg/L predicts more than sixfold increased risk of incurable foot ulceration. PMID- 26864250 TI - W-box and G-box elements play important roles in early senescence of rice flag leaf. AB - Plant cis-elements play important roles in global regulation of gene expression. Based on microarray data from rice flag leaves during early senescence, we identified W-box and G-box cis-elements as positive regulators of senescence in the important rice variety Minghui 63. Both cis-elements were bound by leaf senescence-specific proteins in vitro and influenced senescence in vivo. Furthermore, combination of the two elements drove enhanced expression during leaf senescence, and copy numbers of the cis-elements significantly affected the levels of expression. The W-box is the cognate cis-element for WRKY proteins, while the G-box is the cognate cis-element for bZIP, bHLH and NAC proteins. Consistent with this, WRKY, bZIP, bHLH and NAC family members were overrepresented among transcription factor genes up-regulated according during senescence. Crosstalk between ABA, CTK, BR, auxin, GA and JA during senescence was uncovered by comparing expression patterns of senescence up-regulated transcription factors. Together, our results indicate that hormone-mediated signaling could converge on leaf senescence at the transcriptional level through W-box and G-box elements. Considering that there are very few documented early senescence-related cis-elements, our results significantly contribute to understanding the regulation of flag leaf senescence and provide prioritized targets for stay-green trait improvement. PMID- 26864252 TI - Snoring intensity and excessive daytime sleepiness in subjects without obstructive sleep apnea. AB - OBJECTIVES/HYPOTHESIS: Snoring and excessive daytime sleepiness (EDS) are major obstructive sleep apnea (OSA) symptoms. Snorers with apnea/hypopnea index < 5 are designated "simple snorers" and do not meet OSA criteria. This study aimed to explore a possible association between snoring intensity and EDS defined as Epworth Sleepiness Scale (ESS) scores >= 11 in non-OSA subjects. STUDY DESIGN: Prospective cohort study. METHODS: From a total of 2,225 subjects who underwent polysomnography (PSG), 307 simple snorers qualified for the study and were assessed for snoring intensity and ESS score. The correlation between PSG-based snoring intensity measurements and ESS score was evaluated. A prediction model for EDS was derived using multivariate logistic regression. RESULTS: Subjects with EDS tended to be male and of heavier body habitus. Although both genders exhibited similar snoring intensities, men had higher ESS scores than women. A strong linear correlation was demonstrated between the maximal snoring intensity and the ESS score. Maximal snoring sound and male gender were shown to be predictors of EDS, with odds ratios of 1.93 (95% confidence interval [CI]:1.63 2.26, P < .001) and 3.70 (95% CI: 1.29-12.5, P = .01), respectively. CONCLUSIONS: In a population of non-OSA subjects referred to a PSG study, snoring intensity was associated with EDS in both men and women. A positive linear correlation was observed between snoring intensities and ESS scores. Additional studies are needed to further consolidate the evidence regarding the implications of simple snoring for public health. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1696-1701, 2016. PMID- 26864253 TI - Lingual Thyroid Ectopia: Diagnostic SPECT/CT Imaging and Radioactive Iodine Treatment. AB - BACKGROUND: Lingual thyroid is a rare abnormality of thyroid development that is usually treated conservatively with levothyroxine replacement. Rarely, it becomes large enough to cause obstructive symptoms in the oral cavity, requiring definitive treatment. PATIENT FINDINGS: This study reports on three patients with lingual thyroid treated with radioactive iodine-131 ((131)I) with successful radioablation of their ectopic thyroid tissues. Measurement of 24-hour radioactive iodine uptake within thyroidal tissues and hybrid single-photon emission computed tomography/computed tomography imaging using either iodine-123 or technetium-99m pertechnetate scans were performed in all patients demonstrating the location and size of lingual thyroid and absence of an orthotopic thyroid gland. SUMMARY: The aim of this study was to describe nonsurgical management of obstructive lingual thyroid tissue with (131)I therapy for lingual thyroid radioablation. Patients were prepared with a low-iodine diet and levothyroxine withdrawal prior to radioablation for optimizing (131)I uptake in ectopic thyroid tissues. Hybrid single-photon emission computed tomography/computed tomography measurement of anatomic size of lingual thyroid tissue and radioactive iodine uptake guided the selection of therapeutic doses, resulting in administration of 10.7, 17.5, and 15.4 mCi of (131)I, respectively. There were no post-therapy complications, and clinical follow-up demonstrated resolution of obstructive oropharyngeal symptoms. CONCLUSIONS: Ectopic lingual thyroid tissue is rarely associated with obstructive oropharyngeal symptoms due to progressive enlargement. Radioiodine therapy with (131)I is an effective treatment modality for ablation of ectopic thyroid tissue as an alternative to surgery. PMID- 26864254 TI - The effect of educational program on stress, anxiety and depression of the mothers of neonates having colostomy. AB - OBJECTIVE: One of the problems that mothers of neonates having colostomy face is their disability in caring colostomy at home. This article is going to demonstrate the impact of educational program for these mothers on their sense of empowerment in caring their neonates. METHODS: This clinical trial was performed in the Neonatal Intensive Care Units (NICUs) to evaluate the level of stress, anxiety and depression of mothers of neonates having colostomy before and after the educational program. In this program, 42 mothers were divided into two groups: experimental group (21 mothers who went under educational plan) and control group (21 mothers who only received the routine care). The levels of stress, anxiety and depression in all mothers were evaluated before and after the educational program with DASS 21 questionnaire. RESULTS: The results showed that educational program in the NICU for experimental groups made them independent and also empowered to care better for their babies. In addition, their depression, anxiety and stress levels were decreased. CONCLUSION: Since the educational program led to a decrease in the levels of stress, anxiety and depression in mothers, this program is recommended to mothers of neonates having colostomy. PMID- 26864255 TI - Regioselective deprotection of the monosaccharide-bearing thiocyanomethyl group at the anomeric position monitored by reversed-phase HPLC method. AB - In the current work, the investigation and development of a chemo-enzymatic approach for the synthesis of neo-glycoproteins have been studied. This strategy is based on the regioselective enzymatic hydrolysis of peracetylated monosaccharide, functionalized at the anomeric position (C1) as 1-thio-(S cyanomethyl) group, a precursor of the 2- iminomethoxyethyl thioglycosides-linker for protein glycosylation, catalyzed by immobilized enzymes to obtain selectively monodeprotected compounds. The use of this activation in C1 is the most frequently used strategy for glycoprotein preparation. The selected biocatalysts are the lipase from Candida rugosa and the acetyl xylan esterase from Bacillus pumilus. A reversed-phase high-performance liquid-chromatographic (HPLC) method for monitoring the regioselective deprotection reaction has been developed. The developed HPLC method was used as a fingerprint to follow the hydrolysis of substrate 1 to substrate 1a and to determine its purity and yield. Moreover, the obtained compound was further purified by flash chromatography. The obtained compound 1a was further characterized using (1) H, (13) C NMR, correlation spectroscopy (COSY) and heteronuclear multiple bond correlation. The resulting product can be used as an intermediate for the preparation of di- and more complex oligosaccharides aimed at protein conjugation. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864256 TI - Tumor metabolism, cancer cell transporters, and microenvironmental resistance. AB - Cancer cells reprogram their metabolic machineries to enter into permanent glycolytic pathways. The full reason for such reprogramming takes place is unclear. However, this metabolic switch is not made in vain for the lactate that is generated and exported outside cells is reused by other cells. This results in the generation of a pH gradient between the low extracellular pH that is acidic (pHe) and the higher cytosolic alkaline or near neutral pH (pHi) environments that are tightly regulated by the overexpression of several pumps and ion channels (e.g. NHE-1, MCT-1, V-ATPase, CA9, and CA12). The generation of this unique pH gradient serves as a determining factor in defining "tumor fitness". Tumor fitness is the capacity of the tumor to invade and metastasize due to its ability to reduce the efficiency of the immune system and confer resistance to chemotherapy. In this article, we highlight the importance of tumor microenvironment in mediating the failure of chemotherapeutic agents. PMID- 26864258 TI - C15049. Taraxerol 4-Methoxybenzoate, an in vitro Inhibitor of Photosynthesis Isolated from Pavonia multiflora A. St-Hil. (Malvaceae). AB - A phytochemical study of Pavonia multiflora A. St.-Hil. (Malvaceae) led to the isolation through chromatographic techniques of ten secondary metabolites: vanillic acid (1), ferulic acid (2), p-hydroxybenzoic acid (3), p-coumaric acid (4), loliolide (5), vomifoliol (6), 4,5-dihydroblumenol A (7), 3-oxo-alpha-ionol (9), blumenol C (10), and taraxerol 4-methoxybenzoate (8), the latter being a novel metabolite. Their structures were identified by 1 H- and 13 C-NMR, using one- and two-dimensional techniques, and X-ray crystallography. In this work, we report the effect of compounds 5 and 8 on several photosynthetic activities in an attempt to search for new compounds as potential herbicide agents that affect photosynthesis. Both compounds inhibited the electron flow from H2 O to methylviologen; therefore, they act as Hill-reaction inhibitors. Using polarographic techniques and studies of the fluorescence of chlorophyll a, the interaction sites of these compounds were located at photosystem II. This article is protected by copyright. All rights reserved. PMID- 26864257 TI - Host adaptation and unexpected symbiont partners enable reef-building corals to tolerate extreme temperatures. AB - Understanding the potential for coral adaptation to warming seas is complicated by interactions between symbiotic partners that define stress responses and the difficulties of tracking selection in natural populations. To overcome these challenges, we characterized the contribution of both animal host and symbiotic algae to thermal tolerance in corals that have already experienced considerable warming on par with end-of-century projections for most coral reefs. Thermal responses in Platygyra daedalea corals from the hot Persian Gulf where summer temperatures reach 36 degrees C were compared with conspecifics from the milder Sea of Oman. Persian Gulf corals had higher rates of survival at elevated temperatures (33 and 36 degrees C) in both the nonsymbiotic larval stage (32-49% higher) and the symbiotic adult life stage (51% higher). Additionally, Persian Gulf hosts had fixed greater potential to mitigate oxidative stress (31-49% higher) and their Symbiodinium partners had better retention of photosynthetic performance under elevated temperature (up to 161% higher). Superior thermal tolerance of Persian Gulf vs. Sea of Oman corals was maintained after 6-month acclimatization to a common ambient environment and was underpinned by genetic divergence in both the coral host and symbiotic algae. In P. daedalea host samples, genomewide SNP variation clustered into two discrete groups corresponding with Persian Gulf and Sea of Oman sites. Symbiodinium within host tissues predominantly belonged to ITS2 rDNA type C3 in the Persian Gulf and type D1a in the Sea of Oman contradicting patterns of Symbiodinium thermal tolerance from other regions. Our findings provide evidence that genetic adaptation of both host and Symbiodinium has enabled corals to cope with extreme temperatures in the Persian Gulf. Thus, the persistence of coral populations under continued warming will likely be determined by evolutionary rates in both, rather than single, symbiotic partners. PMID- 26864259 TI - Multimethod, multistate Bayesian hierarchical modeling approach for use in regional monitoring of wolves. AB - In many cases, the first step in large-carnivore management is to obtain objective, reliable, and cost-effective estimates of population parameters through procedures that are reproducible over time. However, monitoring predators over large areas is difficult, and the data have a high level of uncertainty. We devised a practical multimethod and multistate modeling approach based on Bayesian hierarchical-site-occupancy models that combined multiple survey methods to estimate different population states for use in monitoring large predators at a regional scale. We used wolves (Canis lupus) as our model species and generated reliable estimates of the number of sites with wolf reproduction (presence of pups). We used 2 wolf data sets from Spain (Western Galicia in 2013 and Asturias in 2004) to test the approach. Based on howling surveys, the naive estimation (i.e., estimate based only on observations) of the number of sites with reproduction was 9 and 25 sites in Western Galicia and Asturias, respectively. Our model showed 33.4 (SD 9.6) and 34.4 (3.9) sites with wolf reproduction, respectively. The number of occupied sites with wolf reproduction was 0.67 (SD 0.19) and 0.76 (0.11), respectively. This approach can be used to design more cost-effective monitoring programs (i.e., to define the sampling effort needed per site). Our approach should inspire well-coordinated surveys across multiple administrative borders and populations and lead to improved decision making for management of large carnivores on a landscape level. The use of this Bayesian framework provides a simple way to visualize the degree of uncertainty around population-parameter estimates and thus provides managers and stakeholders an intuitive approach to interpreting monitoring results. Our approach can be widely applied to large spatial scales in wildlife monitoring where detection probabilities differ between population states and where several methods are being used to estimate different population parameters. PMID- 26864261 TI - Pure white-light and colour-tuning of Eu(3+)-Gd(3+)-containing metallopolymer. AB - Direct white-light (CIE coordinate of x = 0.333, y = 0.335, CCT of 5455 K and CRI of 82) with a high luminous efficiency (18.4%) was achieved in the first example of Eu(3+)-Gd(3+)-containing metallopolymer Poly(2-co-NVK-co-4), which also showed tunable purplish-blue to white to yellow-green photoluminescence. PMID- 26864260 TI - Defining a stem cell hierarchy in the intestine: markers, caveats and controversies. AB - The past decade has appreciated rapid advance in identifying the once elusive intestinal stem cell (ISC) populations that fuel the continual renewal of the epithelial layer. This advance was largely driven by identification of novel stem cell marker genes, revealing the existence of quiescent, slowly- and active cycling ISC populations. However, a critical barrier for translating this knowledge to human health and disease remains elucidating the functional interplay between diverse stem cell populations. Currently, the precise hierarchical and regulatory relationships between these ISC populations are under intense scrutiny. The classical theory of a linear hierarchy, where quiescent and slowly-cycling stem cells self-renew but replenish an active-cycling population, is well established in other rapidly renewing tissues such as the haematopoietic system. Efforts to definitively establish a similar stem cell hierarchy within the intestinal epithelium have yielded conflicting results, been difficult to interpret, and suggest non-conventional alternatives to a linear hierarchy. While these new and potentially paradigm-shifting discoveries are intriguing, the field will require development of a number of critical tools, including highly specific stem cell marker genes along with more rigorous experimental methodologies, to delineate the complex cellular relationships within this dynamic organ system. PMID- 26864262 TI - Chemotherapy-Induced Nausea and Vomiting Prophylaxis: Practice Within the Children's Oncology Group. AB - BACKGROUND: The Children's Oncology Group (COG) has endorsed a clinical practice guideline (CPG) for acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis in children with cancer. This project aims to describe current acute CINV prophylaxis practice at COG sites and the gap between this practice and CPG recommendations. PROCEDURE: Two surveys were developed. The first survey, sent to 94 cancer control and supportive care responsible individuals (CCL RIs) at 94 COG institutions, asked if the institution had a standardized approach to practice and focused on antiemetic agent choice. The second survey, sent to 54 pharmacists at COG sites where the CCL RI indicated that there was a standardized approach to CINV prophylaxis practice, focused on antiemetic dosing. Survey results were described and analyzed for consistency with the CPG recommendations. RESULTS: Among the 69 respondents to the first survey, 54 (78%) stated that their institutions have a standardized approach to CINV prophylaxis practice. However, antiemetic choice varied widely among respondents. Results from the 36 respondents to the second survey also demonstrated significant antiemetic dosing practice variability. Frequent sources of deviation from CPG recommendations were as follows: antiemetic choice when corticosteroids are contraindicated, dexamethasone dosing, aprepitant use in children less than 12 years, and aprepitant use in the presence of a known or suspected drug interaction. CONCLUSIONS: There is a great diversity in the CINV prophylaxis provided to children with cancer at COG sites. Concerted strategies are required to improve awareness of the current CINV prophylaxis CPG and to facilitate CPG-consistent CINV prophylaxis. PMID- 26864266 TI - High-mobility group box protein 1 promotes the survival of myeloid-derived suppressor cells by inducing autophagy. AB - Myeloid-derived suppressor cells are immune-suppressive cells that are elevated in most individuals with cancer, where their accumulation and suppressive activity are driven by inflammation. As myeloid-derived suppressor cells inhibit anti-tumor immunity and promote tumor progression, we are determining how their viability is regulated. Previous studies have established that the damage associated molecular pattern molecule high-mobility group box protein 1 drives myeloid-derived suppressor cell accumulation and suppressive potency and is ubiquitously present in the tumor microenvironment. As high-mobility group box protein 1 also facilitates tumor cell survival by inducing autophagy, we sought to determine if high-mobility group box protein 1 regulates myeloid-derived suppressor cell survival through induction of autophagy. Inhibition of autophagy increased the quantity of apoptotic myeloid-derived suppressor cells, demonstrating that autophagy extends the survival and increases the viability of myeloid-derived suppressor cells. Inhibition of high-mobility group box protein 1 similarly increased the level of apoptotic myeloid-derived suppressor cells and reduced myeloid-derived suppressor cell autophagy, demonstrating that in addition to inducing the accumulation of myeloid-derived suppressor cells, high-mobility group box protein 1 sustains myeloid-derived suppressor cell viability. Circulating myeloid-derived suppressor cells have a default autophagic phenotype, and tumor-infiltrating myeloid-derived suppressor cells are more autophagic, consistent with the concept that inflammatory and hypoxic conditions within the microenvironment of solid tumors contribute to tumor progression by enhancing immune-suppressive myeloid-derived suppressor cells. Overall, these results demonstrate that in addition to previously recognized protumor effects, high mobility group box protein 1 contributes to tumor progression by increasing myeloid-derived suppressor cell viability by driving them into a proautophagic state. PMID- 26864268 TI - Decision-making for non-invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy. AB - Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self-determination, independence, and self-sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non-invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi-structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision-making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision-making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision-making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches. PMID- 26864267 TI - IL-36gamma is secreted in microparticles and exosomes by lung macrophages in response to bacteria and bacterial components. AB - Interleukin-36 is a family of novel interleukin-1-like proinflammatory cytokines that are highly expressed in epithelial tissues and several myeloid-derived cell types. Like those of classic interleukin-1 cytokines, the secretion mechanisms of interleukin-36 are not well understood. Interleukin-36gamma secretion in dermal epithelial cells requires adenosine 5'-triphosphate, which suggests a nonclassical mechanism of secretion. In this study, murine pulmonary macrophages and human alveolar macrophages were treated with recombinant pathogen-associated molecular patterns (intact bacteria: Klebsiella pneumoniae or Streptococcus pneumoniae). Cell lysates were analyzed for messenger ribonucleic acid by quantitative real-time polymerase chain reaction, and conditioned medium was analyzed for interleukin-36gamma by enzyme-linked immunosorbent assay, with or without sonication. In addition, conditioned medium was ultracentrifuged at 25,000 g and 100,000 g, to isolate microparticles and exosomes, respectively, and interleukin-36gamma protein was assessed in each fraction by Western blot analysis. Interleukin-36gamma mRNA was induced in both murine and human lung macrophages by a variety of pathogen-associated molecular patterns, as well as heat-killed and live Klebsiella pneumoniae and Streptococcus pneumoniae, and induction occurred in a myeloid differentiation response gene 88-dependent manner. Secretion of interleukin-36gamma protein was enhanced by adenosine 5' triphosphate. Furthermore, extracellular interleukin-36gamma protein detection was markedly enhanced by sonication to disrupt membrane-bound structures. Interleukin-36gamma protein was detected by Western blot in microparticles and exosome fractions isolated by ultracentrifugation. Interleukin-36gamma was induced and secreted from lung macrophages in response to Gram-negative and positive bacterial stimulation. The results suggest that interleukin-36gamma is secreted in a non-Golgi-dependent manner by lung macrophages in response to Gram positive and -negative bacterial challenge. PMID- 26864269 TI - A Latent Class Analysis of Smokeless Tobacco Use in the United States. AB - While there has been an escalating trend in the number of smokeless tobacco uses, mainly snuff, in the United States, it is unclear whether smokeless tobacco users are a homogenous class. The present investigation examines this question and identifies subtypes of smokeless tobacco users in order to better understand the characteristics of these individuals and guide appropriate intervention. Data on smokeless tobacco users (N = 2504) derived from the National Epidemiologic Survey on Alcohol and Related Conditions was employed. A range of antisocial behaviors, from reflecting non-violent deviant acts, irresponsibility, and a disengaged lifestyle, to aggression and violence were used to estimate the number of subtypes of smokeless tobacco users using latent class analysis. Four latent classes emerged: Normative Class (50.2 %), Deviant Class (21.9 %), Disengaging Class (17.2 %), and Antisocial Class (10.5 %). Logistic regression shows that major depression, alcohol use disorder, and marijuana use disorder were associated with Deviant Class (OR's from 2.0 to 10.5). The same array of psychiatric disorders and general anxiety disorder were associated with greater odds of membership in the Disengaging Class (OR's from 2.6 to 7.4). Aforementioned psychiatric disorders and illicit drug use disorder were associated with the Antisocial Class (OR's from 3.8 to 38.1). Findings indicate that smokeless tobacco users are a heterogeneous population that may benefit from differential intervention strategies. PMID- 26864270 TI - Correlates and outcomes related to periprocedural myocardial injury during percutaneous coronary intervention for chronic total occlusion: Results from a prospective, single center PCI registry. AB - BACKGROUND: There is increasing interest in percutaneous coronary intervention (PCI) for chronic total occlusions (CTO). Periprocedural myocardial injury (PMI) post CTO PCI is not uncommon, but true incidence and implications of PMI are not well understood. OBJECTIVES: This study aimed to investigate risk factors for PMI post CTO PCI and its implications for the 1-year clinical outcome of a Chinese population. METHODS: Baseline characteristics, procedure features, and major adverse cardiac events (MACE) at 1 year were assessed in 629 consecutive patients who underwent CTO PCI. PMI was diagnosed as an elevation of creatine kinase MB >=3 times ULN 12-24 hr post procedure. Multivariate analysis was performed to determine the correlates of PMI and MACE at 1-year follow-up. RESULTS: In total, PMI was detected in 115 patients (18.3%). Compared with patients without PMI, those with PMI had a higher percentage of previous coronary artery bypass grafting (CABG), right coronary occlusion and side branch occlusion, and technical success was lower in the PMI group (90.4% vs. 96.7%, P = 0.003). One year MACE-free survival was reduced in the PMI group (87.8% vs. 95.9%, P = 0.001). The final TIMI flow 0-1 (OR 2.23, 95%CI 1.06-4.87, P = 0.02), side branch occlusion (OR 2.67, 95%CI 1.19-7.11, P = 0.009), retrograde PCI (OR 1.35, 95%CI 1.10-2.74, P = 0.04), and history of prior CABG (OR 2.41, 95%CI 1.38-5.91, P = 0.01) were independent risk factors for the occurrence of PMI. CONCLUSIONS: In this unique Chinese cohort, PMI post CTO PCI was associated with several clinical and angiographic factors and exerts an adverse effect on 1-year clinical outcomes. PMID- 26864271 TI - beta-Defensins: Work in Progress. AB - Defensins are a group of antimicrobial peptides (AMPs) found in different living organisms, and are involved in the first line of defense in the innate immune response against pathogens. The increase in the resistance of bacteria to conventional antibiotics and the need for new antibiotics has stimulated interest in the use of AMPs as new therapeutic agents. The inducible nature of human defensin genes suggests that it is possible to increase the endogenous production by utilizing small molecules of various origins to enhance, even selectively, the expression of these peptides. In the light of their role in immunomodulation, angiogenesis, wound healing, inflammation and cancer, as well as their antimicrobial activity, it is possible induce their expression or create analogs with increased specific activity or various degrees of selectivity, or obtain human defensins with genetic engineering to optimize the potency and safety in order to reduce cytotoxicity and potential proinflammatory activity and susceptibility to protease and salt. Restoring the balance between immunostimulating and immunosuppressive molecules may be an important strategy to correct expression defects in specific diseases. PMID- 26864272 TI - Crystal Structure of CYP106A2 in Substrate-Free and Substrate-Bound Form. AB - CYP106A2 from Bacillus megaterium ATCC 13368 is known as a bacterial steroid hydroxylase that is also capable of hydroxylating a variety of terpenoids. To analyze the substrate specificity of this enzyme further, different resin acids of the abietane and pimarane types were tested with regard to binding and conversion. Product formation could be shown for all tested substrates. Spectroscopic studies revealed type I binding spectra for isopimaric acid, but dehydroabietic acid did not induce a high-spin shift of the enzyme. Interestingly, binding of abietic acid resulted in a type II difference spectrum typical for nitrogenous inhibitors. Co-crystallization of CYP106A2 with abietic acid and structure determination revealed bending of the heme cofactor when abietic acid was bound in the active site. Quantum chemical calculations strongly suggest that this heme distortion is the cause of the unusual spectroscopic characteristics. PMID- 26864274 TI - Rapid and efficient synthesis of alpha(1-2)mannobiosides. AB - alpha(1,2)mannobiosides with different substituents at the reducing end have been synthesized by a common strategy using benzoyls as the permanent protecting groups and an acetyl as the orthogonal protecting group at position C2 of the glycosyl acceptor. The new synthetic strategy has been performed remarkably reducing the number of purification steps, the time of synthesis (less than 72 hours) and improving the overall yield at least three times with respect to the best procedure described in the literature at the moment. Additionally, this protecting group strategy is compatible with the presence of azido groups and the use of Cu catalyzed azide alkyne cycloaddition (CuAAC) also called "click chemistry" for conjugating the alpha(1-2)mannobiosides to different scaffolds for the preparation of mannosyl multivalent systems. PMID- 26864275 TI - CoNVaDING: Single Exon Variation Detection in Targeted NGS Data. AB - We have developed a tool for detecting single exon copy-number variations (CNVs) in targeted next-generation sequencing data: CoNVaDING (Copy Number Variation Detection In Next-generation sequencing Gene panels). CoNVaDING includes a stringent quality control (QC) metric, that excludes or flags low-quality exons. Since this QC shows exactly which exons can be reliably analyzed and which exons are in need of an alternative analysis method, CoNVaDING is not only useful for CNV detection in a research setting, but also in clinical diagnostics. During the validation phase, CoNVaDING detected all known CNVs in high-quality targets in 320 samples analyzed, giving 100% sensitivity and 99.998% specificity for 308,574 exons. CoNVaDING outperforms existing tools by exhibiting a higher sensitivity and specificity and by precisely identifying low-quality samples and regions. PMID- 26864276 TI - SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment. AB - Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials. PMID- 26864273 TI - The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy. AB - Bruton's tyrosine kinase (BTK) mediates B cell signaling and is also present in innate immune cells but not T cells. BTK propagates B cell receptor (BCR) responses to antigen-engagement as well as to stimulation via CD40, toll-like receptors (TLRs), Fc receptors (FCRs) and chemokine receptors. Importantly, BTK can modulate signaling, acting as a "rheostat" rather than an "on-off" switch; thus, overexpression leads to autoimmunity while decreased levels improve autoimmune disease outcomes. Autoreactive B cells depend upon BTK for survival to a greater degree than normal B cells, reflected as loss of autoantibodies with maintenance of total antibody levels when BTK is absent. This review describes contributions of BTK to immune tolerance, including studies testing BTK inhibitors for treatment of autoimmune diseases. PMID- 26864278 TI - Synthesis of Capped A(II)B(VI) Nanoparticles for Fluorescent Biomarkers. AB - The conditions for growing CdS nanoparticles suitable for the visualization of biological tissues were theoretically studied and experimentally checked. The optimal ranges for pH values and precursors' concentrations were determined. The applicability of the mercaptoethanol-capped nanoparticles for in vitro luminescence visualization of several cellular forms in histological specimens of human placenta has been proven. PMID- 26864277 TI - Systematic Exploration of Biotransformation Reactions of Amine-Containing Micropollutants in Activated Sludge. AB - The main removal process for polar organic micropollutants during activated sludge treatment is biotransformation, which often leads to the formation of stable transformation products (TPs). Because the analysis of TPs is challenging, the use of pathway prediction systems can help by generating a list of suspected TPs. To complete and refine pathway prediction, comprehensive biotransformation studies for compounds exhibiting pertinent functional groups under environmentally relevant conditions are needed. Because many polar organic micropollutants present in wastewater contain one or several amine functional groups, we systematically explored amine biotransformation by conducting experiments with 19 compounds that contained 25 structurally diverse primary, secondary, and tertiary amine moieties. The identification of 144 TP candidates and the structure elucidation of 101 of these resulted in a comprehensive view on initial amine biotransformation reactions. The reactions with the highest relevance were N-oxidation, N-dealkylation, N-acetylation, and N-succinylation. Whereas many of the observed reactions were similar to those known for the mammalian metabolism of amine-containing xenobiotics, some N-acylation reactions were not previously described. In general, different reactions at the amine functional group occurred in parallel. Finally, recommendations on how these findings can be implemented to improve microbial pathway prediction of amine containing micropollutants are given. PMID- 26864279 TI - Amorphous mixed-metal hydroxide nanostructures for advanced water oxidation catalysts. AB - The design of highly efficient, durable, and earth-abundant catalysts for the oxygen evolution reaction (OER) is crucial in order to promote energy conversion and storage processes. Here, we synthesize amorphous mixed-metal (Ni-Fe) hydroxide nanostructures with a homogeneous distribution of Ni/Fe as well as a tunable Ni/Fe ratio by a simple, facile, green and low-cost electrochemical technique, and we demonstrate that the synthesized amorphous nanomaterials possess ultrahigh activity and super long-term cycle stability in the OER process. The amorphous Ni0.71Fe0.29(OH)x nanostructure affords a current density of 10 mA cm(-2) at an overpotential of a mere 0.296 V and a small Tafel slope of 58 mV dec(-1), while no deactivation is detected in the CV testing even up to 30 000 cycles, which suggests the promising application of these amorphous nanomaterials in electrochemical oxidation. Meanwhile, the distinct catalytic activities among these amorphous Ni-Fe hydroxide nanostructures prompts us to take notice of the composition of the alloy hydroxides/oxides when studying their catalytic properties, which opens an avenue for the rational design and controllable preparation of such amorphous nanomaterials as advanced OER electrocatalysts. PMID- 26864280 TI - The protective effects of intranasal administration of IL-12 given before influenza virus infection and the negative effects of IL-12 treatment given after viral infection. AB - To investigate whether the administration of IL-12 is effective against influenza virus infection, mice were intranasally administered IL-12 for three consecutive days and then infected with a non-lethal dose of the influenza virus. The IL-12 treated mice were more resistant to the virus than control mice with respect to the remission of body weight loss, virus burden, pro-inflammatory cytokine production, and inflammatory cell infiltration in the lungs. The number of NK cells and the level of NK cell cytotoxicity significantly increased in the lungs of the mice treated with IL-12 before infection compared to that observed in control mice, leading to promptly eliminate the viral-infected cells. Unexpectedly, all of mice that received IL-12 treatment after being infected with a non-lethal dose of the virus died as a result of their high virus burden and pro-inflammatory cytokine production in the lungs. One possibility of the mechanisms was considered to be activation of myeloid-derived suppressor cell (MDSC), which has immune suppressive function, in the lungs. Thus, IL-12 treatment has opposite effects depending on whether it is administered before or after infection. These results demonstrate the potential risks of immune modulating therapies such as administration of exogenous cytokine or neutralization of cytokine. J. Med. Virol. 88:1487-1496, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864282 TI - Static and Dynamic Magnetization of Gradient FeNi Alloy Nanowire. AB - FeNi binary nanowires with gradient composition are fabricated by the electrodeposition method. The energy dispersive spec-trometer line-sweep results show that the composition changes gradually along the wire axis. The gradient FeNi nanowires exhibit polycrystalline and crystal twinning at different areas along the nanowire axis, with a textured face-centered cubic structure. The static and dynamic magnetization properties are characterized by a hysteresis loop and ferromagnetic reso-nance with pumping frequencies from 12- 40 GHz. The linear dispersion of the pumping frequency vs: the resonance field has been observed with the applied bias field higher than the saturation field, corresponding to the hysteresis loop. The field-sweep linewidths decrease with increasing pumping frequency, and the frequency-sweep linewidths stay nearly constant at the unsaturated region. The linewidth is a Gilbert type at the saturated state, with damping of 0.035 +/- 0.003. Compared with the damping of the homogeneous composition FeNi nanowire (a = 0.044 +/- 0.005), the gradient FeNi nanowire may have less eddy current damping, which could make it an alternative candidate for spintronics and microstrip antennas. PMID- 26864283 TI - Ir-Cu nanoframes: one-pot synthesis and efficient electrocatalysts for oxygen evolution reaction. AB - Herein, we achieved successful synthesis of uniform Ir-Cu nanoframes with highly open structures by a facile one-pot strategy. The key to obtain alloy nanoframes was the careful control over the reduction and galvanic replacement reactions between different metals. The as-prepared Ir-Cu was proved to be an effective template for constructing trimetallic nanoframes. Furthermore, these highly open nanostructures exhibited excellent electrocatalytic performance toward oxygen evolution reaction in alkaline media. PMID- 26864284 TI - Fabrication and Enhanced Photoelectrochemical Performance of MoS2/S-Doped g-C3N4 Heterojunction Film. AB - We report on a novel MoS2/S-doped g-C3N4 heterojunction film with high visible light photoelectrochemical (PEC) performance. The heterojunction films are prepared by CVD growth of S-doped g-C3N4 film on indium-tin oxide (ITO) glass substrates, with subsequent deposition of a low bandgap, 1.69 eV, visible-light response MoS2 layer by hydrothermal synthesis. Adding thiourea into melamine as the coprecursor not only facilitates the growth of g-C3N4 films but also introduces S dopants into the films, which significantly improves the PEC performance. The fabricated MoS2/S-doped g-C3N4 heterojunction film offers an enhanced anodic photocurrent of as high as ~1.2 * 10(-4) A/cm(2) at an applied potential of +0.5 V vs Ag/AgCl under the visible light irradiation. The enhanced PEC performance of MoS2/S-doped g-C3N4 film is believed due to the improved light absorption and the efficient charge separation of the photogenerated charge at the MoS2/S-doped g-C3N4 interface. The convenient preparation of carbon nitride based heterojunction films in this work can be widely used to design new heterojunction photoelectrodes or photocatalysts with high performance for H2 evolution. PMID- 26864285 TI - Electronic Resources About Infant Growth for Parents and Pediatric Trainees Overestimate Normal Growth. PMID- 26864287 TI - Personalization, self-advocacy and inclusion: An evaluation of parent-initiated supported living schemes for people with intellectual and developmental disabilities in the Netherlands. AB - This study focused on parent-initiated supported living schemes in the South of the Netherlands and the ability of these living schemes to enhance participation, choice, autonomy and self-advocacy for people with intellectual or developmental disabilities through personalized planning, support and care. Based on in-depth interviews with tenants, parents and caregivers, findings included that parent initiated supported housing schemes made steps towards stimulating self-advocacy and autonomy for tenants. However, overprotective and paternalistic attitudes expressed by a significant number of parents, as well as structural constraints affecting the living schemes, created obstacles to tenants' personal development. The study calls for consideration of interdependence as a model for the relationship of parents and adult offspring with disabilities. The benefits and tensions inherent within this relationship must be taken into consideration during inclusive community building. PMID- 26864286 TI - Number of Diverticulitis Episodes Before Resection and Factors Associated With Earlier Interventions. AB - IMPORTANCE: Despite professional recommendations to delay elective colon resection for patients with uncomplicated diverticulitis, early surgery (after <3 preceding episodes) appears to be common. Several factors have been suggested to contribute to early surgery, including increasing numbers of younger patients, a lower threshold to operate laparoscopically, and growing recognition of "smoldering" (or nonrecovering) diverticulitis episodes. However, the relevance of these factors in early surgery has not been well tested, and most prior studies have focused on hospitalizations, missing outpatient events and making it difficult to assess guideline adherence in earlier interventions. OBJECTIVE: To describe patterns of episodes of diverticulitis before surgery and factors associated with earlier interventions using inpatient, outpatient, and antibiotic prescription claims. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a nationwide retrospective cohort study from January 1, 2009, to December 31, 2012. The dates of the analysis were July 2014 to May 2015. Participants were immunocompetent adult patients (age range, 18-64 years) with incident, uncomplicated diverticulitis. EXPOSURE: Elective colectomy for diverticulitis. MAIN OUTCOMES AND MEASURES: Inpatient, outpatient, and antibiotic prescription claims for diverticulitis captured in the MarketScan (Truven Health Analytics) databases. RESULTS: Of 87 461 immunocompetent patients having at least 1 claim for diverticulitis, 6.4% (n = 5604) underwent a resection. The final study cohort comprised 3054 nonimmunocompromised patients who underwent elective resection for uncomplicated diverticulitis, of whom 55.6% (n = 1699) were male. Before elective surgery, they had a mean (SD) of 1.0 (0.9) inpatient claims, 1.5 (1.5) outpatient claims, and 0.5 (1.2) antibiotic prescription claims related to diverticulitis. Resection occurred after fewer than 3 episodes in 94.9% (2897 of 3054) of patients if counting inpatient claims only, in 80.5% (2459 of 3054) if counting inpatient and outpatient claims only, and in 56.3% (1720 of 3054) if counting all types of claims. Based on all types of claims, patients having surgery after fewer than 3 episodes were of similar mean age compared with patients having delayed surgery (both 47.7 years, P = .91), were less likely to undergo laparoscopy (65.1% [1120 of 1720] vs 70.8% [944 of 1334], P = .001), and had more time between the last 2 episodes preceding surgery (157 vs 96 days, P < .001). Patients with health maintenance organization or capitated insurance plans had lower rates of early surgery (50.1% [247 of 493] vs 57.4% [1429 of 2490], P = .01) than those with other insurance plan types. CONCLUSIONS AND RELEVANCE: After considering all types of diverticulitis claims, 56.3% (1720 of 3054) of elective resections for uncomplicated diverticulitis occurred after fewer than 3 episodes. Earlier surgery was not explained by younger age, laparoscopy, time between the last 2 episodes preceding surgery, or financial risk-bearing for patients. In delivering value-added surgical care, factors driving early, elective resection for diverticulitis need to be determined. PMID- 26864289 TI - Realizing both selective adsorption and efficient regeneration using adsorbents with photo-regulated molecular gates. AB - A new generation of smart adsorbents was designed by grafting photo-responsive molecules onto the pore entrances of mesoporous silica. These molecules act as the gates of the mesopores, which are reversibly closed/opened upon light irradiation. Our smart adsorbents thus realize both selective adsorption and efficient desorption, which is highly expected for adsorption but impossible for traditional adsorbents with fixed pore entrances. PMID- 26864288 TI - Label-free proteomic analysis of the hydrophobic membrane protein complement in articular chondrocytes: a technique for identification of membrane biomarkers. AB - CONTEXT: There is insufficient knowledge about the chondrocyte membranome and its molecular composition. OBJECTIVE: To develop a Triton X-114 based separation technique using nanoLC-MS/MS combined with shotgun proteomics to identify chondrocyte membrane proteins. MATERIALS AND METHODS: Articular chondrocytes from equine metacarpophalangeal joints were separated into hydrophobic and hydrophilic fractions; trypsin-digested proteins were analysed by nanoLC-MS/MS. RESULTS: A total of 315 proteins were identified. The phase extraction method yielded a high proportion of membrane proteins (56%) including CD276, S100-A6 and three VDAC isoforms. DISCUSSION: Defining the chondrocyte membranome is likely to reveal new biomarker targets for conventional and biological drug discovery. PMID- 26864292 TI - Discrimination Against People With Dermatologic Diseases. PMID- 26864293 TI - Biopsy--What's in the Name? PMID- 26864294 TI - The Evolution of Laser Technology in Dermatology. PMID- 26864295 TI - Crazy in Love. PMID- 26864296 TI - Endoscopic resection of rectal granular-cell tumor using elastic band ligation. AB - Granular cell tumor (GCT) is a rare neoplasm that develops in the gut's submucosal layer. We report the case of a male with a history of surgically excised colon neoplasm where a rectal polyp was identified during a follow-up endoscopy. The lesion, eventually identified as a GCT, was endoscopically removed by band ligation-assisted mucosectomy. This may be the second report of a colorectal GCT successfully managed using band ligation, and the first one on a rectal GCT excised with this technique. PMID- 26864297 TI - Synchronous second primary cancers in patients with squamous esophageal cancer: clinical features and survival outcome. AB - BACKGROUND/AIMS: Unexpected diagnosis of synchronous second primary cancers (SPC) complicates physicians' decision-making because clinical details of squamous esophageal cancer (EC) patients with SPC have been limited. We evaluated clinical features and treatment outcomes of patients with synchronous SPC detected during the initial staging of squamous EC. METHODS: We identified a total of 317 consecutive patients diagnosed with squamous EC. Relevant clinical and cancer specific information were reviewed retrospectively. RESULTS: EC patients with synchronous SPC were identified in 21 patients (6.6%). There were significant differences in median age (70 years vs. 63 years, p = 0.01), serum albumin level (3.3 g/dL vs. 3.9 g/dL, p < 0.01) and body mass index (20.4 kg/m(2) vs. 22.8 kg/m(2), p = 0.01) between EC patients with and without SPC. Head and neck, lung and gastric cancers accounted for 18.2%, 22.7%, and 18.2% of SPC, respectively. Positron emission tomography-computed tomography (PET-CT) detected four cases (18.2%) of SPC that were missed on CT. Management plans were altered in 13 of 21 patients (61.9%) with detected SPC. Curative esophagectomy was attempted in 28.6% of EC patients with SPC (vs. 59.1% of patients without SPC; p = 0.006). EC patients with SPC had significantly lower 5-year survival than patients without SPC (10.6% vs. 36.7%, p = 0.008). CONCLUSIONS: Synchronous SPC were found in 6.6% of squamous EC patients, and PET-CT contributed substantially to the detection of synchronous SPC. EC patients with SPC had poor survival due to challenges of providing stage-appropriate treatment. PMID- 26864299 TI - Microscopic polyangiitis with crescentic glomerulonephritis initially presenting as acute pancreatitis. PMID- 26864298 TI - The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis. AB - BACKGROUND/AIMS: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. METHODS: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. RESULTS: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 +/- 6.31 vs. 4.16 +/- 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). CONCLUSIONS: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis. PMID- 26864300 TI - Structural complexity of simple Fe2O3 at high pressures and temperatures. AB - Although chemically very simple, Fe2O3 is known to undergo a series of enigmatic structural, electronic and magnetic transformations at high pressures and high temperatures. So far, these transformations have neither been correctly described nor understood because of the lack of structural data. Here we report a systematic investigation of the behaviour of Fe2O3 at pressures over 100 GPa and temperatures above 2,500 K employing single crystal X-ray diffraction and synchrotron Mossbauer source spectroscopy. Crystal chemical analysis of structures presented here and known Fe(II, III) oxides shows their fundamental relationships and that they can be described by the homologous series nFeO.mFe2O3. Decomposition of Fe2O3 and Fe3O4 observed at pressures above 60 GPa and temperatures of 2,000 K leads to crystallization of unusual Fe5O7 and Fe25O32 phases with release of oxygen. Our findings suggest that mixed-valence iron oxides may play a significant role in oxygen cycling between earth reservoirs. PMID- 26864301 TI - Combination of non-ablative fractional photothermolysis and 0.1% tacrolimus ointment is efficacious for treating idiopathic guttate hypomelanosis. AB - BACKGROUND: The efficacy of fractional photothermolysis and topical use of calcineurin inhibitors as treatments of idiopathic guttate hypomelanosis (IGH) have been reported. Data on combination treatments are lacking. OBJECTIVES: To evaluate the efficacy and safety of 1550-nm ytterbium/erbium fiber laser combined with 0.1% tacrolimus ointment as a treatment of IGH. METHODS: In each patient with IGH, two lesions were assigned as a treatment group, whilst two lesions on another side were chosen as control. Four treatments by fractional 1550-nm ytterbium/erbium fiber laser were delivered every four weeks combined with a twice daily topical application of 0.1% tacrolimus ointment. Lesional skin color was measured by colorimeter. Digital and dermoscopic digital photographs were taken and evaluated by three dermatologists. RESULTS: A total of 120 lesions were treated. Combination treatment normalized the relative lightness index of IGH which reached statistical significant compared with the control at week 12, after three sessions of laser treatment (p = 0.026). Physicians' assessment score revealed that 91.67% of the lesions on treatment side showed an improvement. Swelling and redness were the most common side effects which spontaneously resolved. CONCLUSION: Fractional 1550-nm ytterbium/erbium fiber laser combined with topical 0.1% tacrolimus ointment was effective for IGH. PMID- 26864302 TI - Magnetic susceptibility of actinide(iii) cations: an experimental and theoretical study. AB - In a previous paper, the influence of radioactive decay (alpha and beta(-)) on magnetic susceptibility measurements by the Evans method has been demonstrated by the study of two americium isotopes. To characterize more accurately this phenomenon and particularly its influence on the Curie law, a new study has been performed on two uranium isotopes ((238)U and (233)U) and on tritiated water ((3)H2O). The results on the influence of alpha emissions have established a relationship between changes in the temperature dependence and the radioactivity in solution. Regarding the beta(-) emissions, less influence was observed while no temperature dependence linked to this kind of radioactive emission could be identified. Once magnetic susceptibility measurements of actinide(iii) cations were corrected from radioactivity effects, methods of quantum chemistry have been used on free ions and aquo complexes to calculate the electronic structure explaining the magnetic properties of Pu(iii), Am(iii) and Cm(iii). The ligand field effect on the magnetic behavior (the Curie constant and temperature independent susceptibilities) was analyzed by considering different solvation environments. PMID- 26864303 TI - Basics of PD-1 in self-tolerance, infection, and cancer immunity. AB - Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as "checkpoints" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD 1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule. PMID- 26864304 TI - The Tactile Window to Consciousness is Characterized by Frequency-Specific Integration and Segregation of the Primary Somatosensory Cortex. AB - We recently proposed that besides levels of local cortical excitability, also distinct pre-stimulus network states (windows to consciousness) determine whether a near-threshold stimulus will be consciously perceived. In the present magnetoencephalography study, we scrutinised these pre-stimulus network states with a focus on the primary somatosensory cortex. For this purpose participants performed a simple near-threshold tactile detection task. Confirming previous studies, we found reduced alpha and beta power in the somatosensory region contralateral to stimulation prior to correct stimulus detection as compared to undetected stimuli, and stronger event-related responses following successful stimulus detection. As expected, using graph theoretical measures, we also observed modulated pre-stimulus network level integration. Specifically, the right primary somatosensory cortex contralateral to stimulation showed an increased integration in the theta band, and additionally, a decreased integration in the beta band. Overall, these results underline the importance of network states for enabling conscious perception. Moreover, they indicate that also a reduction of irrelevant functional connections contributes to the window to consciousness by tuning pre-stimulus pathways of information flow. PMID- 26864305 TI - MicroRNA-223 controls the expression of histone deacetylase 2: a novel axis in COPD. AB - Reduced activity of histone deacetylase 2 (HDAC2) has been described in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms resulting in decreased expression of this important epigenetic modifier remain unknown. Here, we employed several in vitro experiments to address the role of microRNAs (miRNAs) on the regulation of HDAC2 in endothelial cells. Manipulation of miRNA levels in human pulmonary artery endothelial cells (HPAEC) was achieved by using electroporation with anti-miRNAs and miRNA mimics. Target prediction software identified miR-223 as a potential repressor of HDAC2. In subsequent stimulation experiments using inflammatory cytokines known to be increased in patients with COPD, miR-223 was found to be significantly induced. Functional analysis demonstrated that overexpression of miR-223 decreased HDAC2 expression and activity in HPAEC. Conversely, HDAC2 expression and activity was preserved in anti-miR-223-treated cells. Direct miRNA-target interaction was confirmed by reporter gene assay. In a next step, reduced expression of HDAC2 was found to increase the levels of the chemokine fractalkine (CX3CL1). In vivo studies confirmed elevated expression levels of miR-223 in mice exposed to cigarette smoke and in emphysematous lung tissue from LPS-treated mice. Moreover, a significant inverse correlation of miR-223 and HDAC2 expression was found in two independent cohorts of COPD patients. These data emphasize that miR-223, the most prevalent miRNA in COPD, controls expression and activity of HDAC2 in pulmonary cells, which, in turn, might alter the expression profile of chemokines. This pathway provides a novel pathogenic link between dysregulated miRNA expression and epigenetic activity in COPD. KEY MESSAGES: Histone deacetylase 2 is directly targeted by miR-223. Levels of miR-223 are induced by interleukin-1beta and tumor necrosis factor-alpha. miR-223 controls the expression of fractalkine by targeting histone deacetylase 2. miR-223 levels are increased in COPD mouse models. miR-223 levels inversely correlate with HDAC2 expression in COPD patients. PMID- 26864307 TI - Patient rated outcomes study into the surgical interventions available for the rheumatoid hand and wrist. AB - INTRODUCTION: A multitude of surgical interventions are recognised for the treatment of the rheumatoid hand and wrist, however there seems to be a distinct lack of patient rated outcome measures (PROMs) studies reporting on the efficacy of these procedures. The aim of this study was to assess the PROMs related to hand and wrist surgery in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: A single surgeon series identified 94 patients (133 hands) with RA who had undergone one of eight surgical procedures (Swanson's arthroplasty, finger joint or wrist arthrodesis, carpal tunnel decompression, posterior interosseous nerve denervation, RA nodule excision, synovectomy/tenosynovectomy and tendon repair/release) with a mean follow-up period of 3 years. The primary outcome measures were the same for all patients and comprised the validated modified score for the assessment and quantification of chronic rheumatoid affections of the hand (M-SACRAH) and a separate satisfaction questionnaire. RESULTS: Highly significant improvements in both function and pain scores are reported across the cohort as a whole following hand surgery, with this pattern replicated within all of the operative subgroups. In keeping with these favourable results very high levels of overall satisfaction were reported with 93 % of patients reporting themselves to be very or fairly satisfied with their procedure. CONCLUSIONS: Overall, patient reported outcomes in functional, stiffness and pain domains of the M-SACRAH questionnaire appear very favourable across the range of surgical procedures that can be performed in the rheumatoid hand. We believe this data supports the use of all the procedures explored, and will be helpful in patient guidance. PMID- 26864306 TI - Far-infrared promotes burn wound healing by suppressing NLRP3 inflammasome caused by enhanced autophagy. AB - Understanding the underlying molecular mechanisms in burn wound progression is crucial to providing appropriate diagnoses and designing therapeutic regimens for burn patients. When inflammation becomes unregulated, recurrent, or excessive, it interferes with burn wound healing. Autophagy, which is a homeostatic and catabolic degradation process, was found to protect against ischemic injury, inflammatory diseases, and apoptosis in some cases. In the present study, we investigated whether far-infrared (FIR) could ameliorate burn wound progression and promote wound healing both in vitro and in a rat model of deep second-degree burn. We found that FIR induced autophagy in differentiated THP-1 cells (human monocytic cells differentiated to macrophages). Furthermore, FIR inhibited both the NLRP3 inflammasome and the production of IL-1beta in lipopolysaccharide activated THP-1 macrophages. In addition, FIR induced the ubiquitination of ASC, which is the adaptor protein of the inflammasome, by increasing tumor necrosis factor receptor-associated factor 6 (TRAF6), which is a ubiquitin E3 ligase. Furthermore, the exposure to FIR then promoted the delivery of inflammasome to autophagosomes for degradation. In a rat burn model, FIR ameliorated burn-induced epidermal thickening, inflammatory cell infiltration, and loss of distinct collagen fibers. Moreover, FIR enhanced autophagy and suppressed the activity of the NLRP3 inflammasome in the rat skin tissue of the burn model. Based on these results, we suggest that FIR-regulated autophagy and inflammasomes will be important for the discovery of novel therapeutics to promote the healing of burn wounds. KEY MESSAGES: Far-infrared (FIR) induced autophagy in THP-1 macrophages. FIR suppressed the NLRP3 inflammasome through the activation of autophagy. FIR induced the ubiquitination of ASC by increasing TRAF6. FIR ameliorated burn wound progression and promoted wound healing in a rat burn model. PMID- 26864309 TI - Task-Specific Balance Training Improves the Sensory Organisation of Balance Control in Children with Developmental Coordination Disorder: A Randomised Controlled Trial. AB - Sensory organisation of balance control is compromised in children with developmental coordination disorder (DCD). A randomised controlled trial involving 88 children with DCD was conducted to evaluate the efficacy of a task specific balance training (functional-movement training, FMT) programme in improving balance deficits in a DCD population. The DCD participants were randomly assigned to either a FMT group or a control group. The FMT group received two training sessions/ week for 3 months. Measurements of the participants' sensory organisation (somatosensory, vestibular and visual ratios), balance and motor proficiency (Movement Assessment Battery for Children, MABC scores) and center of pressure sway velocity (Unilateral Stance Test, UST scores) were taken at baseline, immediately after FMT and 3 months after FMT. The FMT group showed greater improvements than the controls in somatosensory ratio at 3 and 6 months (all P < 0.001), but the within-group changes were not significant (P > 0.05). The results of both the MABC and the UST also indicated that the balance performance of the FMT group was significantly better than that of the control group at 3 and 6 months (all P < 0.05). Task-specific balance training was found to marginally improve the somatosensory function and somewhat improve the balance performance of children with DCD. PMID- 26864308 TI - IL-33 mediates reactive eosinophilopoiesis in response to airborne allergen exposure. AB - BACKGROUND: Exposure to aeroallergens induces eosinophilic airway inflammation in patients with asthma and allergic airway diseases. The circulating number of eosinophils in peripheral blood is relatively small, leading us to hypothesize that bone marrow needs to be engaged quickly to meet the demands of the tissues. METHODS: To investigate the communication between the lungs and bone marrow, we used acute allergen exposure and airway inflammation models in mice. Gene deficient mice and cytokine reporter mice as well as in vitro cell culture models were used to dissect the mechanisms. RESULTS: Naive BALB/c mice produced increased numbers of eosinophil precursors and mature eosinophils in the bone marrow when their airways were exposed to a common fungal allergen, Alternaria alternata. Expression of IL-5 and IL-33 increased rapidly in the lungs, but not in the bone marrow. Sera from allergen-exposed mice promoted eosinophilopoiesis in bone marrow cells from naive mice, which was blocked by anti-IL-5 antibody. Mice deficient in the IL-33 receptor ST2 (i.e., Il1rl1(-/-) mice) were unable to increase their serum levels of IL-5 and allergen-induced eosinophilopoiesis in the bone marrow after allergen exposure. Finally, group 2 innate lymphoid cells (ILC2s) in the lungs showed robust expression of IL-5 after Alternaria exposure. CONCLUSIONS: These finding suggests that lung IL-33, through innate activation of ILC2s and their production of IL-5, plays a key role in promoting acute reactive eosinophilopoiesis in the bone marrow when naive animals are exposed to airborne allergens. Therefore, bone marrow eosinophilopoiesis may be affected by atmospheric environmental conditions. PMID- 26864310 TI - Association between personality traits and future choice of specialisation among Swedish doctors: a cross-sectional study. AB - BACKGROUND: Medical students' choice of their future specialty is influenced by several factors, including working conditions and type of patient relations. The aim of this study was to investigate the association between the choice of specialty and personality traits. METHODS: This is a cross-sectional questionnaire-based study of 399 alumni from Karolinska Institutet Medical School who were assumed to undergo specialty training at the time of the survey in 2013. The Big Five Inventory was used to assess the personality traits extraversion, agreeableness, conscientiousness, neuroticism and openness to experience. Medical specialties were categorised as primary care, psychiatry, internal medicine and surgical and hospital service specialties. Adjustments were made for demographic factors and the method of selection for medical school admission. RESULTS: The response rate was 72% (n=289, of which 262 were in training to become specialists). Among these, surgeons scored lower in agreeableness than physicians in primary care, internal medicine and hospital services. Psychiatrists and hospital service physicians showed lower conscientiousness compared with surgeons. CONCLUSIONS: We found distinctive differences in personality traits between medical specialties even after adjusting for other potential explanatory variables. Since there are differences between specialties, for example, surgeons and psychiatrists, this supports previous findings that personality may affect medical students' specialty choice also in a Swedish setting. PMID- 26864311 TI - Passive Targeting of Cyclophosphamide-Loaded Carbonate Apatite Nanoparticles to Liver Impedes Breast Tumor Growth in a Syngeneic Model. AB - Despite being widely used for treating cancer, chemotherapy is accompanied by numerous adverse effects as a result of systemic distribution and nonspecific interactions of the drugs with healthy tissues, eventually leading to therapeutic inefficacy and chemoresistance. Cyclophosphamide (Cyp) as one of the chemotherapeutic pro-drugs is activated in liver and used to treat breast cancer in high dose and in combination with other drugs. In an attempt to reduce the off target effects and enhance the therapeutic efficacy, pH-sensitive carbonate apatite nanoparticles that had predominantly and size-dependently been localized in liver following intravenous administration, were employed to electrostatically immobilize Cyp and purposely deliver it to the liver for activation. Cyp-loaded particles formed by simple 30 min incubation at 37oC of the DMEM (pH 7.4) medium containing CaCl2 and Cyp, enhanced in vitro cytotoxicity at different degrees depending on the cell types. The size of the particles could be tightly controlled by the amount of CaCl2 required to prepare the particles and thus the bio-distribution pattern inside different organs of the body. Unlike the small particles (~ 200 nm), the large size particles (~ 600 nm) which were more efficiently accumulated in liver, significantly reduced the tumor volume following intravenous injection in 4T1-induced murine breast cancer model at a very low dose (0.17 mg/Kg) of the drug initially added for complex formation, thus shedding light on the potential applications of the Cyp-loaded nano formulations in the treatment of breast cancer. PMID- 26864312 TI - Targeting Inflammatory Bowel Diseases by Nanocarriers Loaded with Small and Biopharmaceutical Anti-Inflammatory Drugs. AB - Nanotechnology has emerged as a promising strategy toward inflammatory bowel disease (IBD) treatment. Nano-sized drug delivery systems exhibit an increased accumulation in inflamed tissues due to their nanometer size and present the ability to overcome the challenging inflamed colonic barriers (i.e. thick mucus layer, disrupted epithelium, altered colonic transit time). Moreover, nanocarriers are able to increase the amount of drug present at the colonic site decreasing their associated systemic side effects and increasing their efficacy. This review aims to analyze the nanoparticulate systems that have been evaluated for IBD treatment based on (i) the strategy followed towards an increased colonic accumulation and/or permeation, (ii) the small or biopharmaceutical antiinflammatory drug encapsulated within the nanocarriers and (iii) the polymer(s) used for their preparation, highlighting the profits and the drawbacks of each of the candidates based on reported results. PMID- 26864313 TI - Rapid Preparation of Silsesquioxane-Based Ionic Liquids. AB - Three new hybrid ionic liquids (ILs) based on cage silsesquioxane (SQ) were rapidly prepared in high yields from octa(mercaptopropyl)silsesquioxane and 1 allyl-3-methylimidazolium salts (Br(-), BF4(-), PF6(-)) through the photochemical thiol-ene reaction. These SQ-based ILs exhibited low glass transition temperatures and good thermal stability. The unique amphiphilic nature of these hybrid ILs cause them to self-assemble into perfect vesicles with "yolk-shell" structures, in which cages formed the "yolk" due to their aggregation and outer anions formed the "shell". PMID- 26864314 TI - Satellite gravity gradient grids for geophysics. AB - The Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite aimed at determining the Earth's mean gravity field. GOCE delivered gravity gradients containing directional information, which are complicated to use because of their error characteristics and because they are given in a rotating instrument frame indirectly related to the Earth. We compute gravity gradients in grids at 225 km and 255 km altitude above the reference ellipsoid corresponding to the GOCE nominal and lower orbit phases respectively, and find that the grids may contain additional high-frequency content compared with GOCE-based global models. We discuss the gradient sensitivity for crustal depth slices using a 3D lithospheric model of the North-East Atlantic region, which shows that the depth sensitivity differs from gradient to gradient. In addition, the relative signal power for the individual gradient component changes comparing the 225 km and 255 km grids, implying that using all components at different heights reduces parameter uncertainties in geophysical modelling. Furthermore, since gravity gradients contain complementary information to gravity, we foresee the use of the grids in a wide range of applications from lithospheric modelling to studies on dynamic topography, and glacial isostatic adjustment, to bedrock geometry determination under ice sheets. PMID- 26864315 TI - Corrigendum to "Identification of a pentatricopeptide repeat RNA editing factor in Physcomitrella patens chloroplasts" [FEBS Lett. 588 (2014) 4060-4064]. PMID- 26864316 TI - Corrigendum to "Subunit unbinding mechanics of dimeric wheat germ agglutinin (WGA) studied by atomic force microscopy" [FEBS Lett. 588 (2014) 4472-4477]. PMID- 26864319 TI - Different Susceptibility of B-Type Natriuretic Peptide (BNP) and BNP Precursor (proBNP) to Cleavage by Neprilysin: The N-Terminal Part Does Matter. AB - BACKGROUND: Protease neprilysin is known to be responsible for the degradation of natriuretic peptides. A recent heart failure (HF) drug, LCZ696 (Entresto(TM)), that combines a neprilysin inhibitor and an angiotensin II receptor inhibitor was suggested to augment circulating B-type natriuretic peptide (BNP) concentrations, making the results of BNP measurements diagnostically ambiguous. Because the main form of measured BNP in HF patients is represented by its uncleaved precursor, proBNP, it is important to know the susceptibility of proBNP to cleavage by neprilysin. METHODS: BNP 1-32 and nonglycosylated and glycosylated forms of proBNP 1-108 were incubated with neprilysin for different time periods. BNP immunoreactivity was analyzed using 2 sandwich immunoassays: one utilizing monoclonal antibody (mAb) KY-BNP-II (epitope 14-21) as capture with mAb 50E1 (epitope 26-32) for detection and a single-epitope sandwich BNP (SES-BNP) immunoassay specific to the epitope 11-17. Mass-spectrometry was applied to determine the sites of BNP cleavage. RESULTS: In contrast to BNP, both forms of proBNP were resistant to degradation by neprilysin. The SES-BNP assay was much less susceptible to the BNP cleavage by neprilysin compared with the immunoassay utilizing antibodies specific to the region 14-21, comprising the site Arg17 Ile18, known as the site of BNP cleavage by neprilysin. CONCLUSIONS: These findings suggest that modulation of neprilysin activity by specific inhibitors may not greatly influence the circulating concentrations of immunoreactive BNP, mostly represented in HF by proBNP, which is not susceptible to neprilysin. The different susceptibility of the BNP regions to neprilysin-dependent degradation highlights the importance of the choice of epitopes for reliable BNP immunodetection. PMID- 26864320 TI - One-Pot Synthesis of CoSex -rGO Composite Powders by Spray Pyrolysis and Their Application as Anode Material for Sodium-Ion Batteries. AB - A simple one-pot synthesis of metal selenide/reduced graphene oxide (rGO) composite powders for application as anode materials in sodium-ion batteries was developed. The detailed mechanism of formation of the CoSe(x)-rGO composite powders that were selected as the first target material in the spray pyrolysis process was studied. The crumple-structured CoSe(x)-rGO composite powders prepared by spray pyrolysis at 800 degrees C had a crystal structure consisting mainly of Co0.85 Se with a minor phase of CoSe2. The bare CoSe(x) powders prepared for comparison had a spherical shape and hollow structure. The discharge capacities of the CoSe(x)-rGO composite and bare CoSe(x) powders in the 50th cycle at a constant current density of 0.3 A g(-1) were 420 and 215 mA h g(-1), respectively, and their capacity retentions measured from the second cycle were 80 and 46%, respectively. The high structural stability of the CoSe(x)-rGO composite powders for repeated sodium-ion charge and discharge processes resulted in superior sodium-ion storage properties compared to those of the bare CoSe(x) powders. PMID- 26864318 TI - PERK Integrates Oncogenic Signaling and Cell Survival During Cancer Development. AB - Unfolded protein responses (UPR), consisting of three major transducers PERK, IRE1, and ATF6, occur in the midst of a variety of intracellular and extracellular challenges that perturb protein folding in the endoplasmic reticulum (ER). ER stress occurs and is thought to be a contributing factor to a number of human diseases, including cancer, neurodegenerative disorders, and various metabolic syndromes. In the context of neoplastic growth, oncogenic stress resulting from dysregulation of oncogenes such as c-Myc, Braf(V600E) , and HRAS(G12V) trigger the UPR as an adaptive strategy for cancer cell survival. PERK is an ER resident type I protein kinase harboring both pro-apoptotic and pro survival capabilities. PERK, as a coordinator through its downstream substrates, reprograms cancer gene expression to facilitate survival in response to oncogenes and microenvironmental challenges, such as hypoxia, angiogenesis, and metastasis. Herein, we discuss how PERK kinase engages in tumor initiation, transformation, adaption microenvironmental stress, chemoresistance and potential opportunities, and potential opportunities for PERK targeted therapy. J. Cell. Physiol. 231: 2088-2096, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864321 TI - How providers influence the implementation of provider-initiated HIV testing and counseling in Botswana: a qualitative study. AB - BACKGROUND: Understanding the motivations and perspectives of providers in following guidance and evidence-based policies can contribute to the evidence on how to better implement and deliver care, particularly in resource-constrained settings. This study explored how providers' attitudes and behaviors influenced the implementation of an intervention, provider-initiated HIV testing and counseling, in primary health care settings in Botswana. METHODS: Using a grounded-theory approach, we purposively selected and interviewed 45 providers in 15 facilities in 3 districts and inductively analyzed data for themes and patterns. RESULTS: We found that nurses across facilities and districts were largely resistant to offering and delivering provider-initiated testing and counseling for HIV (PITC) for three reasons: (1) they felt they were overworked and had no time, (2) they felt it was not their job, and (3) they were afraid to counsel patients, particularly fearing a positive HIV test. These factors were largely related to health system constraints that affected the capacity of providers to do their job. An important underlying themes emerged: nurses and lay counselors were unsatisfied with pay and career prospects, which made them unmotivated to work in general. Variations were seen by urban and rural areas: nurses in urban areas felt generally overworked and PITC was seen as contributing to the workload. While nurses in rural areas did not feel overworked, they felt that PITC was not their job and they were unmotivated because of general unhappiness with their rural posts. CONCLUSIONS: The attitudes and behaviors of providers and barriers they faced played a critical role in whether and how PITC was being implemented in Botswana. Provider factors should be considered in the improvement of existing PITC programs and design of new ones. Addressing constraints faced by providers can do more to improve supply of human resources than merely recruiting more providers. PMID- 26864322 TI - Complex clinical and microbiological effects on Legionnaires' disease outcone; A retrospective cohort study. AB - BACKGROUND: Legionnaires' disease (LD) is associated with high mortality rates and poses a diagnostic and therapeutic challenge. Use of the rapid urinary antigen test (UAT) has been linked to improved outcome. We examined the association between the method of diagnosis (UAT or culture) and various clinical and microbiological characteristics and outcome of LD. METHODS: Consecutive patients with pneumonia and confirmation of Legionella infection by a positive UAT and/or a positive culture admitted between the years 2006-2012 to a university hospital were retrospectively studied. Isolated L. pneumophila strains were subject to serogrouping, immunological subtyping and sequence-based typing. Variables associated with 30-day all-cause mortality were analyzed using logistic regression as well as cox regression. RESULTS: Seventy-two patients were eligible for mortality analyses (LD study group), of whom 15.5 % have died. Diagnosis based on positive L. pneumophila UAT as compared to positive culture (OR = 0.18, 95 % CI 0.03-0.98, p = 0.05) and administration of appropriate antibiotic therapy within 2 hospitalization days as compared to delayed therapy (OR = 0.16, 95 % CI 0.03-0.90, p = 0.04) were independently associated with reduced mortality. When controlling for intensive care unit (ICU) admissions, the method of diagnosis became non-significant. Survival analyses showed a significantly increased death risk for patients admitted to ICU compared to others (HR 12.90, 95 % CI 2.78 59.86, p = 0.001) and reduced risk for patients receiving appropriate antibiotic therapy within the first two admissions days compared to delayed therapy (HR 0.13, 95 % CI 0.04-0.05, p = 0.001). Legionella cultures were positive in 35 patients (including 29 patients from the LD study group), of whom 65.7 % were intubated and 37.1 % have died. Sequence type (ST) ST1 accounted for 50.0 % of the typed cases and ST1, OLDA/Oxford was the leading phenon (53.8 %). Mortality rate among patients in the LD study group infected with ST1 was 18.2 % compared to 42.9 % for non-ST1 genotypes (OR = 0.30, 95 % CI 0.05-1.91, p = 0.23). CONCLUSIONS: The study confirms the importance of early administration of appropriate antibiotic therapy and at the same time highlights the complex associations of different diagnostic approaches with LD outcome. Infection with ST1 was not associated with increased mortality. Genotype effects on outcome mandate examination in larger cohorts. PMID- 26864325 TI - The Recognition of STEMI by Paramedics and the Effect of Computer inTerpretation (RESPECT): a randomised crossover feasibility study. AB - BACKGROUND: The appropriate management of patients with ST-segment elevation myocardial infarction (STEMI) depends on accurate interpretation of the 12-lead ECG by paramedics. Computer interpretation messages on ECGs are often provided, but the effect they exert on paramedics' decision-making is not known. The objective of this study was to assess the feasibility of using an online assessment tool, and collect pilot data, for a definitive trial to determine the effect of computer interpretation messages on paramedics' diagnosis of STEMI. METHODS: The Recognition of STEMI by Paramedics and the Effect of Computer inTerpretation (RESPECT) feasibility study was a randomised crossover trial using a bespoke, web-based assessment tool. Participants were randomly allocated 12 of 48 ECGs, with an equal mix of correct and incorrect computer interpretation messages, and STEMI and STEMI-mimics. The nature of the responses required a cross-classified multi-level model. RESULTS: 254 paramedics consented into the study, 205 completing the first phase and 150 completing phase two. The adjusted OR for a correct paramedic interpretation, when the computer interpretation was correct (true positive for STEMI or true negative for STEMI-mimic), was 1.80 (95% CI 0.84 to 4.91) and 0.58 (95% CI 0.41 to 0.81) when the computer interpretation was incorrect (false positive for STEMI or false negative for STEMI-mimic). The intraclass correlation coefficient for correct computer interpretations was 0.33 for participants and 0.17 for ECGs, and for incorrect computer interpretations, 0.06 for participants and 0.01 for ECGs. CONCLUSIONS: Determining the effect of computer interpretation messages using a web-based assessment tool is feasible, but the design needs to take clustered data into account. Pilot data suggest that computer messages influence paramedic interpretation, improving accuracy when correct and worsening accuracy when incorrect. PMID- 26864324 TI - Anti-tumoral, anti-angiogenic and anti-metastatic efficacy of a tetravalent bispecific antibody (TAvi6) targeting VEGF-A and angiopoietin-2. AB - Vascular endothelial growth factor (VEGF)-A blockade has been validated clinically as a treatment for human cancers. Angiopoietin-2 (Ang-2) is a key regulator of blood vessel remodeling and maturation. In tumors, Ang-2 is up regulated and an unfavorable prognostic factor. Recent data demonstrated that Ang 2 inhibition mediates anti-tumoral effects. We generated a tetravalent bispecific antibody (Ang-2-VEGF-TAvi6) targeting VEGF-A with 2 arms based on bevacizumab (Avastin(r)), and targeting Ang-2 with 2 arms based on a novel anti-Ang-2 antibody (LC06). The two Ang-2-targeting single-chain variable fragments are disulfide-stabilized and fused to the C-terminus of the heavy chain of bevacizumab. Treatment with Ang-2-VEGF-A-TAvi6 led to a complete abrogation of angiogenesis in the cornea micropocket assay. Metastatic spread and tumor growth of subcutaneous, orthotopic and anti-VEGF-A resistant tumors were also efficiently inhibited. These data further establish Ang-2-VEGF bispecific antibodies as a promising anti-angiogenic, anti-metastatic and anti-tumor agent for the treatment of cancer. PMID- 26864323 TI - Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells. AB - Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA. PMID- 26864326 TI - Predicting admission at triage: are nurses better than a simple objective score? AB - AIM: We compared two methods of predicting hospital admission from ED triage: probabilities estimated by triage nurses and probabilities calculated by the Glasgow Admission Prediction Score (GAPS). METHODS: In this single-centre prospective study, triage nurses estimated the probability of admission using a 100 mm visual analogue scale (VAS), and GAPS was generated automatically from triage data. We compared calibration using rank sum tests, discrimination using area under receiver operating characteristic curves (AUC) and accuracy with McNemar's test. RESULTS: Of 1829 attendances, 745 (40.7%) were admitted, not significantly different from GAPS' prediction of 750 (41.0%, p=0.678). In contrast, the nurses' mean VAS predicted 865 admissions (47.3%), overestimating by 6.6% (p<0.0001). GAPS discriminated between admission and discharge as well as nurses, its AUC 0.876 compared with 0.875 for VAS (p=0.93). As a binary predictor, its accuracy was 80.6%, again comparable with VAS (79.0%), p=0.18. In the minority of attendances, when nurses felt at least 95% certain of the outcome, VAS' accuracy was excellent, at 92.4%. However, in the remaining majority, GAPS significantly outperformed VAS on calibration (+1.2% vs +9.2%, p<0.0001), discrimination (AUC 0.810 vs 0.759, p=0.001) and accuracy (75.1% vs 68.9%, p=0.0009). When we used GAPS, but 'over-ruled' it when clinical certainty was >=95%, this significantly outperformed either method, with AUC 0.891 (0.877 0.907) and accuracy 82.5% (80.7%-84.2%). CONCLUSIONS: GAPS, a simple clinical score, is a better predictor of admission than triage nurses, unless the nurse is sure about the outcome, in which case their clinical judgement should be respected. PMID- 26864327 TI - Prehospital management and identification of sepsis by emergency medical services: a systematic review. AB - OBJECTIVE: To identify studies describing the accuracy of prehospital sepsis identification and to summarise results of studies of prehospital management of patients with sepsis, severe sepsis or septic shock. METHODS: We conducted a systematic review to retrieve studies that evaluated the prehospital identification or treatment of patients with sepsis by emergency medical services (EMS). Two authors extracted data describing the study characteristics, incidence of sepsis among EMS-transported patients, criteria used to identify sepsis and specific treatments provided to patients with sepsis. When possible, we calculated the sensitivity and specificity of EMS provider diagnosis of sepsis. RESULTS: Our search identified no randomised controlled trials and 16 cohort studies. Eight studies described the identification of sepsis, seven described prehospital management or treatment of sepsis and one described both. The most common approach to the identification of sepsis involved applying systemic inflammatory response syndrome criteria or a combination of vital signs, which had sensitivity ranging from 0.43 to 0.86 when used alone or combined with provider impression. Only four studies collected information required to calculate specificity (0.47-0.87). Meta-analysis was not performed owing to significant heterogeneity and an overall low quality of evidence. A few studies described prehospital sepsis treatment-most commonly intravenous fluid resuscitation. CONCLUSIONS: The evidence suggests that identification of sepsis in the prehospital setting by EMS providers is carried out with varied success, depending on the strategy used; however, high-quality studies are lacking. Relying on provider impression alone had poor sensitivity, but some moderate quality evidence supporting structured screening for sepsis with vital signs criteria demonstrated modest sensitivity and specificity. Additional research to improve diagnostic accuracy and explore improvements in EMS management is needed. PMID- 26864328 TI - SIBLING CONFLICTS IN FULL- AND HALF-SIBLING HOUSEHOLDS IN THE UK. AB - Sibling relations are by nature ambivalent with high levels of both altruistic helping and competition. Higher relatedness is often assumed to reduce the occurrence of conflicts between siblings, but evidence of this has been scarce and mixed. Siblings typically compete over resources and parental attention, and parental constellations vary with sibship types. Since full-siblings compete over the same two biological parents, while half-siblings have only one shared biological parent and often a higher number of parents overall, it is hypothesized that conflicts are more common between full- than half-siblings. This study tested this assumption using the British Millennium Cohort Study (n=7527 children at age 11). Conflicts were measured as children's reports of how much siblings picked on and hurt each other. Households with full-siblings only, maternal half-siblings only, and both full- and maternal half-siblings were compared. The results show that children who were living with only their full siblings were more likely to experience sibling conflicts compared with children living with their maternal half-siblings only. This was the case also after controlling for several potentially confounding variables. The results suggest that differential access to parental resources of available biological and step parents may explain the higher amount of sibling conflict between full- compared with maternal half-siblings. PMID- 26864329 TI - Peri-implant bone adaptations to overloading in rat tibiae: experimental investigations and numerical predictions. AB - OBJECTIVES: (i) To assess the effects of mechanical overloading on implant integration in rat tibiae, and (ii) to numerically predict peri-implant bone adaptation. MATERIALS AND METHODS: Transcutaneous titanium implants were simultaneously placed into both tibiae of rats (n = 40). After 2 weeks of integration, the implants of the right tibiae were stimulated daily for 4 weeks with loads up to 5N (corresponding to peak equivalent strains of 3300 +/- 500 MUepsilon). The effects of stimulation were assessed by ex vivo mechanical tests and quantification of bone mineral density (BMD) in selected regions of interests (ROIs). Specimen-specific finite element models were generated and processed through an iterative algorithm to mimic bone adaptation. RESULTS: Bilateral implantation provoked an unstable integration that worsened when mild (2-4N) external loads were applied. In contrast, a stimulation at 5N tended to "counterbalance" the harmful effects of daily activity and, if applied to well integrated specimens, significantly augmented the implants' resistance to failure (force: +73% P < 0.01, displacement: +50% P < 0.01 and energy: +153% P < 0.01). Specimen-specific numerical predictions were in close agreement with the experimental findings. Both local and overall BMD variations, as well as the implants' lateral stability, were predicted with small errors (0.14 gHA/cm3 and 0.64%, respectively). CONCLUSIONS: The rats' daily activity detrimentally affects implant integration. Conversely, external stimulations of large magnitudes counterbalance this effect and definitively improve integration. These changes can be predicted using the proposed numerical approach. PMID- 26864330 TI - Comparison of the Morphology and Histomorphometry of Spermatogenic Cyst of Three Sharks Species With Diametric Testes. AB - Characterization of the reproductive anatomy of elasmobranchs (sharks, skates, rays, and sawfish) offers unique insights into the evolution of reproductive traits in animals due to their phylogenetic position at the base of the vertebrate tree of life. Yet, despite advances in our understanding of male elasmobranch reproductive physiology and testes histology, very little is known about how testes histomorphometrics varies with male maturation. In this study, we characterize and contrast testes morphology and histomorphology of males at different maturation stages in three shark species with diametric testes development: Prionaceglauca, Rhizoprionodon lalandii, and Mustelus canis. All stages of spermatogenesis were observed in P. glauca and R. lalandii, while for M. canis, only males at early stages of maturation were examined and therefore all the spermatogenesis cells lineage were not present. The number of Sertoli cells increased with cell development by six times in R. lalandii and roughly four times in P. glauca, and were statistically different among stages of spermatogenesis cysts in both species. Statistical differences in cyst diameter and Sertoli cell numbers were observed between P. glauca and R. lalandii. The increase of spermatocyte II cell diameter described for R. Lalandii in this study was not usual to elasmobranch species as compared, for example, to P. glauca. This information proves the importance of studying the testicular development and the process of spermatogenesis is necessary for understanding the reproductive biology of the species, including life cycles and history, variation of reproductive morphology. Anat Rec, 299:759-768, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864331 TI - Risk of end-stage renal disease in systemic lupus erythematosus patients: a nationwide population-based study. AB - OBJECTIVES: The aim of this study was to estimate the risk of end-stage renal disease (ESRD) in systemic lupus erythematosus (SLE) patients. METHODS: A cohort with SLE and non-SLE groups from Taiwan's longitudinal Health Insurance Database year 2000 (LHID2000) was developed. The SLE group was made up of those who were newly diagnosed with SLE in 2000. The non-SLE group with other medical illnesses was made up of those who did not have SLE from 1996 until 2008 and that were also matched 1 : 1 with the SLE group by sex, age and initial diagnosis date (index date); 1196 (1058 women and 138 men) individuals in the SLE group were included in this study. RESULTS: Between 2000 and 2008, 61 (2.55%) individuals (SLE, n = 58 [4.85%]; non-SLE, n = 3 [0.25%]) had incident ESRD requiring renal replacement therapy. The incidence rates of ESRD were 612.8 and 29.3 cases per 100 000 patient-years in the SLE and non-SLE groups, respectively. The incidence of ESRD requiring renal replacement therapy occurred more frequently in male SLE (1157.0; 95% CI 502.4-1811.6) than female SLE cases (545.8; 95% CI 388.1-703.5) per 100 000 person-years (P < 0.001). During the 8-year follow-up, after adjustment for age, sex, hypertension, diabetes and hyperlipidemia, the hazard ratio (HR) for ESRD requiring renal replacement therapy was 18.2 times higher (95% CI: 5.7-58.2, P < 0.001) in the SLE group than in the non-SLE group. CONCLUSIONS: ESRD is more common in SLE than non-SLE patients in this insurance database. Due to the lack of data on initial renal function and the renal parameters, the odds ratios do not represent the risk of ESRD in SLE patients compared to the general population, but only to those with non-SLE chronic illnesses. PMID- 26864332 TI - In vitro and in vivo characterisation of the metabolism and disposition of suvorexant in humans. AB - 1. Suvorexant (MK-4305, Belsomra(r)) is a first-in-class dual orexin receptor antagonist approved in the USA and Japan for the treatment of insomnia. The current studies describe suvorexant's absorption, disposition and potential for CYP-mediated drug interactions in humans. 2. Following single oral administration of [(14)C]suvorexant to healthy human subjects, 90% of the radioactivity was recovered (66% in faeces, 23% in urine), primarily as oxidative metabolites. 3. In plasma, suvorexant and M9 were predominant, accounting for 30 and 37% of the total radioactivity, respectively. Metabolite M17 became more prominent (approaching 10%) following multiple daily doses of unlabelled suvorexant. M9 and M17 are not expected to contribute to the pharmacological activity of suvorexant due to reduced orexin receptor binding affinity and limited brain penetration. 4. CYP3A was determined to be the predominant enzyme mediating suvorexant oxidation. In vitro, suvorexant demonstrated reversible inhibition of CYP3A4 and 2C19 (IC50 ~ 4-5 MUM), and weak time-dependent inhibition of CYP3A4 (KI = 12 MUM, kinact = 0.14 min(-1)). Suvorexant was also a weak inducer of CYP3A4, 1A2 and 2B6. Given the low plasma concentrations at clinical doses, suvorexant was not anticipated to cause significant drug interactions via inhibition and/or induction of major CYPs in vivo. PMID- 26864333 TI - Cost-effectiveness analysis of rapid diagnostic tests for G6PD deficiency in patients with Plasmodium vivax malaria in the Brazilian Amazon. AB - BACKGROUND: The use of primaquine (PQ) for radical treatment of Plasmodium vivax in carriers of G6PD deficiency (G6PDd) constitutes the main factor associated with severe haemolysis in G6PDd. The current study aimed to estimate the incremental cost-effectiveness ratio of using a rapid diagnostic test (RDT) to detect G6PDd in male patients with P. vivax malaria in the Brazilian Amazon, in comparison with the routine indicated by the Programme for Malaria Control, which does not include this evaluation. METHODS: A cost-effectiveness analysis of estimated RDT use was carried out for the Brazilian Amazon for the year 2013, considering the perspective of the Brazilian Public Health System. Using decision trees, estimates were compared for two different RDT strategies for G6PDd in male individuals infected with P. vivax before being prescribed PQ, with the routine indicated in Brazil, which does not include prior diagnosis of G6PDd. The first strategy considered the combined use of RDT BinaxNOW((r)) G6PD (BX-G6PD) in municipalities with more than 100,000 inhabitants and the routine programme (RP) for the other municipalities. Operational limitations related to the required temperature control and venous blood collection currently restrict the use of RDT BX-G6PD in small municipalities. The second strategy considered the use of the RDT CareStartTM G6PD (CS-G6PD) in 100 % of the municipalities. The analysis was carried out for the outcomes: "adequately diagnosed case" and "hospitalization avoided". RESULTS: For the outcome "adequately diagnosed case", comparing the RDT strategies based on RDT with the routine control programme (RP), the CS-G6PD strategy was the most cost-effective, with BX-G6PD extendedly dominating (the ICER of BX-G6PD compared with RP was higher than the ICER of CS-G6PD compared with RP). CS-G6PD dominated the other strategies for the "hospitalization avoided" outcome. CONCLUSION: The CS-G6PD strategy is cost-effective for adequately diagnosing cases and avoiding hospitalization. This information can help in decision-making, both in incorporating prior diagnosis in the use of PQ and to promote greater safety among G6PD deficient individuals in the Brazilian Amazon P. vivax endemic areas. PMID- 26864334 TI - A flexible ratio regression approach for zero-truncated capture-recapture counts. AB - Capture-recapture methods are used to estimate the size of a population of interest which is only partially observed. In such studies, each member of the population carries a count of the number of times it has been identified during the observational period. In real-life applications, only positive counts are recorded, and we get a truncated at zero-observed distribution. We need to use the truncated count distribution to estimate the number of unobserved units. We consider ratios of neighboring count probabilities, estimated by ratios of observed frequencies, regardless of whether we have a zero-truncated or an untruncated distribution. Rocchetti et al. (2011) have shown that, for densities in the Katz family, these ratios can be modeled by a regression approach, and Rocchetti et al. (2014) have specialized the approach to the beta-binomial distribution. Once the regression model has been estimated, the unobserved frequency of zero counts can be simply derived. The guiding principle is that it is often easier to find an appropriate regression model than a proper model for the count distribution. However, a full analysis of the connection between the regression model and the associated count distribution has been missing. In this manuscript, we fill the gap and show that the regression model approach leads, under general conditions, to a valid count distribution; we also consider a wider class of regression models, based on fractional polynomials. The proposed approach is illustrated by analyzing various empirical applications, and by means of a simulation study. PMID- 26864335 TI - Three-dimensional printing of MRI-visible phantoms and MR image-guided therapy simulation. AB - PURPOSE: To demonstrate the use of anatomic MRI-visible three-dimensional (3D) printed phantoms and to assess process accuracy and material MR signal properties. METHODS: A cervical spine model was generated from computed tomography (CT) data and 3D-printed using an MR signal-generating material. Printed phantom accuracy and signal characteristics were assessed using 120 kVp CT and 3 Tesla (T) MR imaging. The MR relaxation rates and diffusion coefficient of the fabricated phantom were measured and 1 H spectra were acquired to provide insight into the nature of the proton signal. Finally, T2 -weighted imaging was performed during cryoablation of the model. RESULTS: The printed model produced a CT signal of 102 +/- 8 Hounsfield unit, and an MR signal roughly 1/3rd that of saline in short echo time/short repetition time GRE MRI (456 +/- 36 versus 1526 +/- 121 arbitrary signal units). Compared with the model designed from the in vivo CT scan, the printed model differed by 0.13 +/- 0.11 mm in CT, and 0.62 +/- 0.28 mm in MR. The printed material had T2 ~32 ms, T2*~7 ms, T1 ~193 ms, and a very small diffusion coefficient less than olive oil. MRI monitoring of the cryoablation demonstrated iceball formation similar to an in vivo procedure. CONCLUSION: Current 3D printing technology can be used to print anatomically accurate phantoms that can be imaged by both CT and MRI. Such models can be used to simulate MRI-guided interventions such as cryosurgeries. Future development of the proposed technique can potentially lead to printed models that depict different tissues and anatomical structures with different MR signal characteristics. Magn Reson Med 77:613-622, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26864336 TI - What is positive youth development and how might it reduce substance use and violence? A systematic review and synthesis of theoretical literature. AB - BACKGROUND: Preventing adolescent substance use and youth violence are public health priorities. Positive youth development interventions are widely deployed often with the aim of preventing both. However, the theorised mechanisms by which PYD is intended to reduce substance use and violence are not clear and existing evaluated interventions are under-theorised. Using innovative methods, we systematically searched for and synthesised published theoretical literature describing what is meant by positive youth development and how it might reduce substance use and violence, as part of a broader systematic review examining process and outcomes of PYD interventions. METHODS: We searched 19 electronic databases, review topic websites, and contacted experts between October 2013 and January 2014. We included studies written in English, published since 1985 that reported a theory of change for positive youth development focused on prevention of smoking, alcohol consumption, drug use or violence in out-of-school settings. Studies were independently coded and quality-assessed by two reviewers. RESULTS: We identified 16 studies that met our inclusion criteria. Our synthesis suggests that positive youth development aims to provide youth with affective relationships and diverse experiences which enable their development of intentional self-regulation and multiple positive assets. These in turn buffer against or compensate for involvement in substance use and violence. Existing literature is not clear on how intentional self-regulation is developed and which specific positive assets buffer against substance use or violence. CONCLUSIONS: Our synthesis provides: an example of a rigorous systematic synthesis of theory literature innovatively applying methods of qualitative synthesis to theoretical literature; a clearer understanding of how PYD might reduce substance use and violence to inform future interventions and empirical evaluations. PMID- 26864337 TI - Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study. AB - CONTEXT: Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors. OBJECTIVE: The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN. MATERIALS AND METHODS: The ethyl acetate and water fractions (1-100 MUg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method. RESULTS AND DISCUSSIONS: The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3',5'-tetrahydroxybibenzyl (2), and 5,7,4'-trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC50 value of 3.15 MUM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC50 value= 14.20 MUM), quercetin-3-O-beta-D-glucopyranoside (6, IC50 value = 19.39 MUM) and quercetin-3-O-beta-D-galactopyranoside (7, IC50 value = 21.80 MUM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3'-processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN. PMID- 26864338 TI - Age-sex-specific ranges of platelet count and all-cause mortality: prospective findings from the MOLI-SANI study. PMID- 26864339 TI - Analysis of Jak2 signaling reveals resistance of mouse embryonic hematopoietic stem cells to myeloproliferative disease mutation. AB - The regulation of hematopoietic stem cell (HSC) emergence during development provides important information about the basic mechanisms of blood stem cell generation, expansion, and migration. We set out to investigate the role that cytokine signaling pathways play in these early processes and show here that the 2 cytokines interleukin 3 and thrombopoietin have the ability to expand hematopoietic stem and progenitor numbers by regulating their survival and proliferation. For this, they differentially use the Janus kinase (Jak2) and phosphatidylinositol 3-kinase (Pi3k) signaling pathways, with Jak2 mainly relaying the proproliferation signaling, whereas Pi3k mediates the survival signal. Furthermore, using Jak2-deficient embryos, we demonstrate that Jak2 is crucially required for the function of the first HSCs, whereas progenitors are less dependent on Jak2. The JAK2V617F mutation, which renders JAK2 constitutively active and has been linked to myeloproliferative neoplasms, was recently shown to compromise adult HSC function, negatively affecting their repopulation and self renewal ability, partly through the accumulation of JAK2V617F-induced DNA damage. We report here that nascent HSCs are resistant to the JAK2V617F mutation and show no decrease in repopulation or self-renewal and no increase in DNA damage, even in the presence of 2 mutant copies. More importantly, this unique property of embryonic HSCs is stably maintained through >=1 round of successive transplantations. In summary, our dissection of cytokine signaling in embryonic HSCs has uncovered unique properties of these cells that are of clinical importance. PMID- 26864340 TI - Polygenic mutations in the cytotoxicity pathway increase susceptibility to develop HLH immunopathology in mice. AB - Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disease. Inherited forms of HLH are caused by biallelic mutations in several effectors of granule-dependent lymphocyte-mediated cytotoxicity. A small proportion of patients with a so-called "secondary" form of HLH, which develops in the aftermath of infection, autoimmunity, or cancer, carry a monoallelic mutation in one or more HLH-associated genes. Although this observation suggests that HLH may have a polygenic mode of inheritance, the latter is very difficult to prove in humans. In order to determine whether the accumulation of partial genetic defects in lymphocyte-mediated cytotoxicity can contribute to the development of HLH, we generated mice that were doubly or triply heterozygous for mutations in HLH-associated genes, those coding for perforin, Rab27a, and syntaxin-11. We found that the accumulation of monoallelic mutations did indeed increase the risk of developing HLH immunopathology after lymphocytic choriomeningitis virus infection. In mechanistic terms, the accumulation of heterozygous mutations in the two degranulation genes Rab27a and syntaxin-11, impaired the dynamics and secretion of cytotoxic granules at the immune synapse of T lymphocytes. In addition, the accumulation of heterozygous mutations within the three genes impaired natural killer lymphocyte cytotoxicity in vivo. The genetic defects can be ranked in terms of the severity of the resulting HLH manifestations. Our results form the basis of a polygenic model of the occurrence of secondary HLH. PMID- 26864342 TI - Highly selective capture of nucleosides with boronic acid functionalized polymer brushes prepared by atom transfer radical polymerization. AB - The nucleoside or modified nucleoside level in biological fluids reflects the pathological or physiological state of the body. Boronate affinity absorbents are widely used to selectively extract nucleosides from complex samples. In this work, a novel functionalized absorbent was synthesized by attaching 4 mercaptophenylboronic acid to gold nanoparticles on modified attapulgite. The surface of the attapulgite was modified by poly(acryloyloxyethyltrimethyl ammonium chloride) by atom transfer radical polymerization, creating many polymer brushes on the surface. The resultant material exhibited superior binding capacity (30.83 mg/g) for adenosine and was able to capture cis-diol nucleosides from 1000-fold interferences. Finally, to demonstrate its potential for biomolecule extraction, this boronate affinity material was used to preconcentrate nucleosides from human urine and plasma. PMID- 26864343 TI - Removal of Pb(II) and Zn(II) from Aqueous Solutions by Raw Crab Shell: A Comparative Study. AB - Removals of Pb(II) and Zn(II) ions from water using crab (Clistocoeloma sinensis) shell particles as biosorbent have been compared in this study. Uptake equilibriums for two ions well described by Langmuir isotherm revealed that crab shell possessed higher uptake capacity for Pb(II) (709 mg/g) than that for Zn(II) (117 mg/g). Kinetics data for the uptake of the two metals were successfully modeled using the pseudo-second-order model, where the initial uptake rate of Pb(II) was much faster than that of Zn(II). Dubinin-Radushkevick modeling and thermodynamic parameters hinted at different uptake mechanisms of Pb(II) and Zn(II) removal by crab shell, attested by FTIR, XRD, FESEM analysis. Pb(II) ion was removed mainly through the chemical reaction, while the uptake of Zn(II) ion onto crab shell was attributed to the chelation and coordination interactions. The polluted river water and laboratory wastewater both satisfied the standards for drinking and irrigation/fishery water, respectively, after being treated with crab shell particles. PMID- 26864344 TI - Severe eye damage in infants with microcephaly is presumed to be due to Zika virus. PMID- 26864341 TI - Normal ABL1 is a tumor suppressor and therapeutic target in human and mouse leukemias expressing oncogenic ABL1 kinases. AB - Leukemias expressing constitutively activated mutants of ABL1 tyrosine kinase (BCR-ABL1, TEL-ABL1, NUP214-ABL1) usually contain at least 1 normal ABL1 allele. Because oncogenic and normal ABL1 kinases may exert opposite effects on cell behavior, we examined the role of normal ABL1 in leukemias induced by oncogenic ABL1 kinases. BCR-ABL1-Abl1(-/-) cells generated highly aggressive chronic myeloid leukemia (CML)-blast phase-like disease in mice compared with less malignant CML-chronic phase-like disease from BCR-ABL1-Abl1(+/+) cells. Additionally, loss of ABL1 stimulated proliferation and expansion of BCR-ABL1 murine leukemia stem cells, arrested myeloid differentiation, inhibited genotoxic stress-induced apoptosis, and facilitated accumulation of chromosomal aberrations. Conversely, allosteric stimulation of ABL1 kinase activity enhanced the antileukemia effect of ABL1 tyrosine kinase inhibitors (imatinib and ponatinib) in human and murine leukemias expressing BCR-ABL1, TEL-ABL1, and NUP214-ABL1. Therefore, we postulate that normal ABL1 kinase behaves like a tumor suppressor and therapeutic target in leukemias expressing oncogenic forms of the kinase. PMID- 26864345 TI - De novo construction of a "Gene-space" for diploid plant genome rich in repetitive sequences by an iterative Process of Extraction and Assembly of NGS reads (iPEA protocol) with limited computing resources. AB - BACKGROUND: The continuing increase in size and quality of the "short reads" raw data is a significant help for the quality of the assembly obtained through various bioinformatics tools. However, building a reference genome sequence for most plant species remains a significant challenge due to the large number of repeated sequences which are problematic for a whole-genome quality de novo assembly. Furthermore, for most SNP identification approaches in plant genetics and breeding, only the "Gene-space" regions including the promoter, exon and intron sequences are considered. RESULTS: We developed the iPea protocol to produce a de novo Gene-space assembly by reconstructing, in an iterative way, the non-coding sequence flanking the Unigene cDNA sequence through addition of next generation DNA-seq data. The approach was elaborated with the large diploid genome of pea (Pisum sativum L.), rich in repetitive sequences. The final Gene space assembly included 35,400 contigs (97 Mb), covering 88 % of the 40,227 contigs (53.1 Mb) of the PsCam_low-copy Unigen set. Its accuracy was validated by the results of the built GenoPea 13.2 K SNP Array. CONCLUSION: The iPEA protocol allows the reconstruction of a Gene-space based from RNA-Seq and DNA-seq data with limited computing resources. PMID- 26864346 TI - Comparison of Doctors' and Breast Cancer Patients' Perceptions of Docetaxel, Epirubicin, and Cyclophosphamide (TEC) Toxicity. AB - In Spain, around 26,000 cases of breast cancer are diagnosed each year, representing nearly 30% of all cancers in women. The aim this study was to compare the perceptions of nonhematologic toxicities after administration of a docetaxel, epirubicin, and cyclophosphamide (TEC) regimen between breast cancer patients and oncologists. Furthermore, the relationship between such adverse events and quality of life (QOL) was evaluated. Cross-sectional study carried out among 92 breast cancer patients who received TEC as neoadjuvant or adjuvant treatment. The main nonhematologic toxicities experienced by breast cancer patients treated with the TEC regimen were asthenia, nausea, dysgeusia, arthralgia, headache, and myalgia. Patients were less likely to be affected by vomiting and peripheral neuropathy. Oncologists seemed to show greater interest in toxicities, such as asthenia, nausea, and diarrhea. Vomiting was the toxicity with the most substantial degree of agreement between oncologist and patient. Toxicities with greater disagreement were dysgeusia, arthralgia, myalgia, asthenia, and headache. Asthenia, dysgeusia, loss of appetite, skin allergies, peripheral edema, abdominal pain, and myalgia were found to significantly affect the QOL. Tolerability and QOL were more favorable in patients treated with pegfilgrastim compared with filgrastim. Oncologists tend to underestimate toxicities experienced by breast cancer patients treated with the TEC regimen. The establishment of a protocol to record these toxicities may reduce that problem. PMID- 26864348 TI - Histamine Receptor Expression in the Gastrointestinal Tract of Dogs. AB - Histamine is an important mediator of many physiological processes including gastrointestinal function that acts via four different histamine receptors (H1R to H4R). Elevated histamine levels and increased HR messenger ribonucleic acid (mRNA) have been shown in humans with gastrointestinal disorders such as irritable bowel syndrome or allergic intestinal diseases. As there is limited knowledge concerning the distribution of histamine receptors (HR) in dogs, one aim of this study was to investigate the expression of histamine 1 receptor (H1R), histamine 2 receptor (H2R) and histamine 4 receptor (H4R) in the canine gastrointestinal tract at protein level using immunohistochemistry. Histamine 1 receptor, H2R and H4R were widely expressed throughout the canine gastrointestinal tract including epithelial, mesenchymal, neuronal and immune cells. In addition, in situ hybridisation was established for detecting canine H4R mRNA. Results showed H4R mRNA to be present in enterocytes, lamina propria immune cells and submucosal plexus in the duodenum and colon of nearly all investigated animals. The results elucidate the importance of HR in the canine gut and represent the basis for investigating their possible impact on canine inflammatory gastrointestinal disorders. PMID- 26864350 TI - Risk analysis for confined space entries: Critical analysis of four tools applied to three risk scenarios. AB - Investigation reports of fatal confined space accidents nearly always point to a problem of identifying or underestimating risks. This paper compares 4 different risk analysis tools developed for confined spaces by applying them to 3 hazardous scenarios. The tools were namely 1. a checklist without risk estimation (Tool A), 2. a checklist with a risk scale (Tool B), 3. a risk calculation without a formal hazard identification stage (Tool C), and 4. a questionnaire followed by a risk matrix (Tool D). Each tool's structure and practical application were studied. Tools A and B gave crude results comparable to those of more analytic tools in less time. Their main limitations were lack of contextual information for the identified hazards and greater dependency on the user's expertise and ability to tackle hazards of different nature. Tools C and D utilized more systematic approaches than tools A and B by supporting risk reduction based on the description of the risk factors. Tool D is distinctive because of 1. its comprehensive structure with respect to the steps suggested in risk management, 2. its dynamic approach to hazard identification, and 3. its use of data resulting from the risk analysis. PMID- 26864347 TI - 5-hydroxymethylcytosine loss is associated with poor prognosis for patients with WHO grade II diffuse astrocytomas. AB - Currently, the reliable prognostic biomarkers for WHO grade II diffuse astrocytomas (DA) are still limited. We investigated the relations between the level of 5-Hydroxymethylcytosine (5hmC), an oxidated production of 5 methylcytosine (5mC) by the ten eleven translocated (TET) enzymes, and clinicopathological features of glioma patients. With an identified anti-5hmC antibody, we performed immunohistochemistry in 287 glioma cases. We detected that 5hmC variably reduced in most gliomas and 5hmC reduction was closely associated with higher pathological grades and shortened survival of glioma patients. In multivariate analysis, 5hmC had no independent prognostic value in the entire patient cohort. However, multivariate analysis within subtypes of gliomas revealed that 5hmC was still a prognostic marker confined to DA. In addition, we detected that IDH1 mutation by DNA sequencing was associated with favorable survival within DA. Lastly, we detected that the combination of 5hmC/KI67 was a useful prognostic marker for restratification of DA. PMID- 26864349 TI - Prognostic value of albumin in patients with head and neck cancer. AB - OBJECTIVES/HYPOTHESIS: Albumin is an indicator of nutritional status and has been investigated as a predictor of cancer survival and perioperative outcomes. This study investigated the prognostic value of preoperative serum albumin in surgical patients with head and neck cancer (HNC). STUDY DESIGN: Retrospective cohort study. METHODS: A chart review was performed of patients who underwent HNC resection over a 6-year period at a single institution. Statistical analyses including Cox proportional hazards models, Pearson's correlation, and logistic regression were used to identify relationships between preoperative serum albumin and postoperative outcomes. Albumin was analyzed as a continuous variable. RESULTS: A total of 604 patients were studied representing all cancer types. There was no association between albumin and pneumonia, flap complications, or length of stay. Albumin was found to have statistically significant inverse associations with overall survival (OS) (hazard ratio [HR] = 0.685, P < .001) and postoperative wound infection (HR = 0.455, P = .001). In multivariate analysis of OS, albumin did not achieve significance as an independent predictor (HR = 0.78, P = .064), whereas hemoglobin, age, and cancer stage remained significant. In a subgroup of 280 patients with upper aerodigestive squamous cell carcinoma (SCCA), albumin maintained significance in multivariate analysis of OS (HR = 0.74, P = .046). When controlling for preoperative radiotherapy, salvage surgery, and cancer stage in multivariate analysis, albumin was a significant predictor of wound infection (OR = 0.55, P = .018). CONCLUSIONS: In patients with HNC, lower preoperative serum albumin is associated with an increased rate of wound infection and poorer OS. The effect on OS is most pronounced in patients with upper aerodigestive SCCA. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:1567-1571, 2016. PMID- 26864351 TI - Induction of labor in twin gestation: lessons from a population based study. AB - INTRODUCTION: The route of delivery and the role of induction of labor in twin gestations are controversial. The aim of this study was to determine the efficacy of induction of labor in twin gestations. METHODS: This retrospective population based cohort study included 4605 twin gestations divided into following groups: 1) spontaneous parturition (n = 2937, 63.78%); 2) induction of labor (n = 653, 14.2%) and 3) elective cesarean delivery (n = 1015, 22.04%). RESULTS: The rate of vaginal delivery in the labor induction group was 81% (529/653). In comparison to the other study groups, induction of labor in twins was independently associated with a 77% reduction in the risk of cesarean delivery (OR 0.23; 95% CI 0.18-0.31) and a 78% reduction in the risk of postpartum death for the second twin (OR 0.22; 95% CI 0.05-0.94). The rate of nulliparity, term delivery and labor dystocia was higher in the induction of labor group (p < 0.001 in all comparisons). CONCLUSIONS: Our results suggest that induction of labor in twin gestation is successful and is independently associated with substantial reduction in the risk of cesarean delivery and postpartum death of the second twin. PMID- 26864352 TI - Aripiprazole once-monthly long-acting injectable for the treatment of schizophrenia. AB - INTRODUCTION: Patient non-adherence increases the risk for relapse and the long term care of schizophrenia. Long-acting injectable (LAI) antipsychotics can decrease this risk by ensuring adherence. An extended formulation, aripiprazole 400 mg once-monthly (AOM 400) LAI (AOM LAI), received regulatory approval in the year 2013 for the treatment of schizophrenia. AOM LAI is the first dopamine D2 partial agonist available in a long-acting formulation for the treatment of schizophrenia. AREAS COVERED: This review covers data on the efficacy and tolerability/safety of AOM LAI. AOM LAI is a lyophilized powder of aripiprazole, with an elimination half-life of 29.9 - 46.5 days, allowing for a 4-week injection interval. Antipsychotic efficacy was documented in a 12-week double blind trial (n = 340) and in two maintenance-of-effect trials: a 38-week trial (n = 662) and a 52-week trial (n = 403). The side effect profile is similar to that of oral aripiprazole. Adverse events (>=5% and at least twice that for placebo) were typically mild or moderate and did not lead to discontinuation: increased weight, akathisia, injection site pain and sedation. The 400 mg dose is tolerated by >90% of patients. Injection does not require additional training of health personnel or post-injection observation. EXPERT OPINION: AOM LAI is an efficacious and well-tolerated antipsychotic treatment for schizophrenia. PMID- 26864353 TI - Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study. AB - A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS-IVa) in rat plasma was established and validated. Plasma samples were pre-treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 * 50 mm, i.d., 3.5 MUm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M - H](-) were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5-1000 ng/mL for CHS-IVa. The recoveries of CHS-IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS-IVa in rats. For oral administration, the plasma concentrations of CHS-IVa increased to a peak value at 0.35 +/- 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS-IVa decreased quickly (t1/2 , 1.59 +/- 0.25 h). The absolute bioavailability of CHS-IVa in rats was 8.63%. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864354 TI - Ethics, research and HIV: lessons learned- a workshop report. AB - Assessing risk for transmission of a blood-borne pathogen requires the use of the hazard and risk model. Infection control is a system that uses a number of individual processes to eliminate or reduce the probability of a hazard occurring. Strategies employed to reduce risk should be rehearsed, used routinely, audited, reviewed, and the results shared. Continuing dental education has improved dental healthcare worker willingness to treat people living with HIV/AIDS (PLWHA) and has decreased negative attitudes and staff fears. Providing care for PLWHA during undergraduate dental school or dental hygiene programme is also associated with a greater willingness to treat. Whether by identifying suspect oral lesions or offering rapid screening tests in the dental setting for HIV, the dental team can play an important role in linkage to confirmatory diagnosis and care with the goal of reducing to zero the number of undiagnosed cases. PMID- 26864355 TI - Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism. AB - BACKGROUND: Elevated plasma concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) are associated with atherosclerosis. However, the determinants of TMAO in humans require additional assessment. OBJECTIVE: We examined cardiometabolic risk factors and pathways associated with TMAO concentrations in humans. DESIGN: A total of 283 individuals (mean +/- SD age: 66.7 +/- 9.0 y) were included in this observational study. Plasma concentrations of trimethylamine, TMAO, choline, lipids, phospholipids, and methyl metabolites were measured. RESULTS: Study participants were divided into 4 groups by median concentrations of TMAO and choline (4.36 and 9.7 MUmol/L, respectively). Compared with the group with TMAO and choline concentrations that were less than the median (n = 82), the group with TMAO and choline concentrations that were at least the median (n = 83) was older and had lower high-density lipoprotein (HDL) cholesterol, phospholipids, and methylation potential, higher creatinine, betaine, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM), and higher percentages of men and subjects with diabetes. The difference in plasma TMAO concentrations between men and women (7.3 +/- 10.0 compared with 5.4 +/- 5.6 MUmol/L, respectively) was NS after adjustment for age and creatinine (P = 0.455). The TMAO:trimethylamine ratio was higher in men (P < 0.001). Diabetes was associated with significantly higher plasma TMAO concentration (8.6 +/- 12.2 compared with 5.4 +/- 5.2 MUmol/L) even after adjustments. Sex and diabetes showed an interactive effect on trimethylamine concentrations (P = 0.010) but not on TMAO concentrations (P = 0.950). Positive determinants of TMAO in a stepwise regression model that applied to the whole group were SAH, trimethylamine, choline, and female sex, whereas plasma phosphatidylcholine was a negative determinant. CONCLUSIONS: High TMAO and choline concentrations are associated with an advanced cardiometabolic risk profile. Diabetes is related to higher plasma TMAO concentrations but also to alterations in interrelated pathways such as lipids, phospholipids, and methylation. Elevated plasma TMAO concentrations likely reflect a specific metabolic pattern characterized by low HDL and phospholipids in addition to hypomethylation. This trial was registered at clinicaltrials.gov as NCT02586181 and NCT02588898. PMID- 26864356 TI - Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. AB - BACKGROUND: Interventions to attenuate the adverse effects of age-related loss of skeletal muscle and function include increased physical activity and nutritional supplementation. OBJECTIVE: This study tested the hypothesis that nutritional supplementation with whey protein (22 g), essential amino acids (10.9 g, including 4 g leucine), and vitamin D [2.5 MUg (100 IU)] concurrent with regular, controlled physical activity would increase fat-free mass, strength, physical function, and quality of life, and reduce the risk of malnutrition in sarcopenic elderly persons. DESIGN: A total of 130 sarcopenic elderly people (53 men and 77 women; mean age: 80.3 y) participated in a 12-wk randomized, double-blind, placebo-controlled supplementation trial. All participants concurrently took part in a controlled physical activity program. We examined body composition with dual energy X-ray absorptiometry, muscle strength with a handgrip dynamometer, and blood biochemical indexes of nutritional and health status, and evaluated global nutritional status, physical function, and quality of life before and after the 12 wk of intervention. RESULTS: Compared with physical activity and placebo, supplementation plus physical activity increased fat-free mass (1.7-kg gain, P < 0.001), relative skeletal muscle mass (P = 0.009), android distribution of fat (P = 0.021), handgrip strength (P = 0.001), standardized summary scores for physical components (P = 0.030), activities of daily living (P = 0.001), mini nutritional assessment (P = 0.003), and insulin-like growth factor I (P = 0.002), and lowered C-reactive protein (P = 0.038). CONCLUSION: Supplementation with whey protein, essential amino acids, and vitamin D, in conjunction with age-appropriate exercise, not only boosts fat-free mass and strength but also enhances other aspects that contribute to well-being in sarcopenic elderly. This trial was registered at clinicaltrials.gov as NCT02402608. PMID- 26864357 TI - Methodologic quality of meta-analyses and systematic reviews on the Mediterranean diet and cardiovascular disease outcomes: a review. AB - BACKGROUND: Several systematic reviews/meta-analyses published within the past 10 y have examined the associations of Mediterranean-style diets (MedSDs) on cardiovascular disease (CVD) risk. However, these reviews have not been evaluated for satisfying contemporary methodologic quality standards. OBJECTIVE: This study evaluated the quality of recent systematic reviews/meta-analyses on MedSD and CVD risk outcomes by using an established methodologic quality scale. The relation between review quality and impact per publication value of the journal in which the article had been published was also evaluated. DESIGN: To assess compliance with current standards, we applied a modified version of the Assessment of Multiple Systematic Reviews (AMSTARMedSD) quality scale to systematic reviews/meta-analyses retrieved from electronic databases that had met our selection criteria: 1) used systematic or meta-analytic procedures to review the literature, 2) examined MedSD trials, and 3) had MedSD interventions independently or combined with other interventions. RESULTS: Reviews completely satisfied from 8% to 75% of the AMSTARMedSD items (mean +/- SD: 31.2% +/- 19.4%), with those published in higher-impact journals having greater quality scores. At a minimum, 60% of the 24 reviews did not disclose full search details or apply appropriate statistical methods to combine study findings. Only 5 of the reviews included participant or study characteristics in their analyses, and none evaluated MedSD diet characteristics. CONCLUSIONS: These data suggest that current meta-analyses/systematic reviews evaluating the effect of MedSD on CVD risk do not fully comply with contemporary methodologic quality standards. As a result, there are more research questions to answer to enhance our understanding of how MedSD affects CVD risk or how these effects may be modified by the participant or MedSD characteristics. To clarify the associations between MedSD and CVD risk, future meta-analyses and systematic reviews should not only follow methodologic quality standards but also include more statistical modeling results when data allow. PMID- 26864358 TI - Best (but oft-forgotten) practices: expressing and interpreting associations and effect sizes in clinical outcome assessments. AB - This article reviews methods used to facilitate the interpretation and evaluation of group-level differences in clinical outcome assessments. These methods complement and supplement tests of statistical significance. Examples, including studies in nutrition, are used to illustrate the application of the interpretation methods for group-level comparisons from experimental or observational studies. In addition, specific pitfalls of evaluating change in meta-analysis studies are described. A set of recommendations is provided. This review is intended as an introduction for the novice and as a refresher for the experienced researcher. PMID- 26864359 TI - Common genetic architecture underlying young children's food fussiness and liking for vegetables and fruit. AB - BACKGROUND: Food fussiness (FF) is common in early childhood and is often associated with the rejection of nutrient-dense foods such as vegetables and fruit. FF and liking for vegetables and fruit are likely all heritable phenotypes; the genetic influence underlying FF may explain the observed genetic influence on liking for vegetables and fruit. Twin analyses make it possible to get a broad-based estimate of the extent of the shared genetic influence that underlies these traits. OBJECTIVE: We quantified the extent of the shared genetic influence that underlies FF and liking for vegetables and fruit in early childhood with the use of a twin design. DESIGN: Data were from the Gemini cohort, which is a population-based sample of twins born in England and Wales in 2007. Parents of 3-y-old twins (n= 1330 pairs) completed questionnaire measures of their children's food preferences (liking for vegetables and fruit) and the FF scale from the Children's Eating Behavior Questionnaire. Multivariate quantitative genetic modeling was used to estimate common genetic influences that underlie FF and liking for vegetables and fruit. RESULTS: Genetic correlations were significant and moderate to large in size between FF and liking for both vegetables (-0.65) and fruit (-0.43), which indicated that a substantial proportion of the genes that influence FF also influence liking. Common genes that underlie FF and liking for vegetables and fruit largely explained the observed phenotypic correlations between them (68-70%). CONCLUSIONS: FF and liking for fruit and vegetables in young children share a large proportion of common genetic factors. The genetic influence on FF may determine why fussy children typically reject fruit and vegetables. PMID- 26864361 TI - Calcium intake and mortality from all causes, cancer, and cardiovascular disease: the Cancer Prevention Study II Nutrition Cohort. AB - BACKGROUND: Calcium intake may be important for bone health, but its effects on other outcomes, including cardiovascular disease (CVD) and cancer, remain unclear. Recent reports of adverse cardiovascular effects of supplemental calcium have raised concerns. OBJECTIVE: We investigated associations of supplemental, dietary, and total calcium intakes with all-cause, CVD-specific, and cancer specific mortality in a large, prospective cohort. DESIGN: A total of 132,823 participants in the Cancer Prevention Study II Nutrition Cohort, who were followed from baseline (1992 or 1993) through 2012 for mortality outcomes, were included in the analysis. Dietary and supplemental calcium information was first collected at baseline and updated in 1999 and 2003. Multivariable-adjusted Cox proportional hazards models with cumulative updating of exposures were used to calculate RRs and 95% CIs for associations between calcium intake and mortality. RESULTS: During a mean follow-up of 17.5 y, 43,186 deaths occurred. For men, supplemental calcium intake was overall not associated with mortality outcomes (P trend > 0.05 for all), but men who were taking >=1000 mg supplemental calcium/d had a higher risk of all-cause mortality (RR: 1.17; 95% CI: 1.03, 1.33), which was primarily attributed to borderline statistically significant higher risk of CVD-specific mortality (RR: 1.22; 95% CI: 0.99, 1.51). For women, supplemental calcium was inversely associated with mortality from all causes [RR (95% CI): 0.90 (0.87, 0.94), 0.84 (0.80, 0.88), and 0.93 (0.87, 0.99) for intakes of 0.1 to <500, 500 to <1000, and >=1000 mg/d, respectively; P-trend < 0.01]. Total calcium intake was inversely associated with mortality in women (P-trend < 0.01) but not in men; dietary calcium was not associated with all-cause mortality in either sex. CONCLUSIONS: In this cohort, associations of calcium intake and mortality varied by sex. For women, total and supplemental calcium intakes are associated with lower mortality, whereas for men, supplemental calcium intake >=1000 mg/d may be associated with higher all-cause and CVD-specific mortality. PMID- 26864360 TI - Vitamin D deficiency in Europe: pandemic? AB - BACKGROUND: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys. OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe. DESIGN: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n= 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. RESULTS: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations. CONCLUSIONS: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population. PMID- 26864362 TI - Higher-protein diets improve indexes of sleep in energy-restricted overweight and obese adults: results from 2 randomized controlled trials. AB - BACKGROUND: Limited and inconsistent research findings exist about the effect of dietary protein intake on indexes of sleep. OBJECTIVE: We assessed the effect of protein intake during dietary energy restriction on indexes of sleep in overweight and obese adults in 2 randomized, controlled feeding studies. DESIGN: For study 1, 14 participants [3 men and 11 women; mean +/- SE age: 56 +/- 3 y; body mass index (BMI; in kg/m(2)): 30.9 +/- 0.6] consumed energy-restricted diets (a 750-kcal/d deficit) with either beef and pork (BP; n = 5) or soy and legume (SL; n = 9) as the main protein sources for 3 consecutive 4-wk periods with 10% (control), 20%, or 30% of total energy from protein (random order). At baseline and the end of each period, the global sleep score (GSS) was assessed with the use of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For study 2, 44 participants (12 men and 32 women; age: 52 +/- 1 y; BMI: 31.4 +/- 0.5) consumed a 3-wk baseline energy-balance diet with 0.8 g protein . kg baseline body mass(-1) . d(-1). Then, study 2 subjects consumed either a normal-protein [NP (control); n = 23] or a high-protein (HP; n = 21) (0.8 compared with 1.5 g . kg(-1) . d(-1), respectively) energy-restricted diet (a 750-kcal/d deficit) for 16 wk. The PSQI was administered during baseline week 3 and intervention weeks 4, 8, 12, and 16. GSSs ranged from 0 to 21 arbitrary units (au), with a higher value representing a worse GSS during the preceding month. RESULTS: In study 1, we showed that a higher protein quantity improved GSSs independent of the protein source. The GSS was higher (P < 0.05) when 10% (6.0 +/- 0.4 au) compared with 20% (5.0 +/- 0.4 au) protein was consumed, with 30% protein (5.4 +/- 0.6 au) intermediate. In study 2, at baseline, the GSS was not different between NP (5.2 +/- 0.5 au) and HP (5.4 +/- 0.5 au) groups. Over time, the GSS was unchanged for the NP group and improved for the HP group (P-group-by-time interaction < 0.05). After intervention (week 16), GSSs for NP and HP groups were 5.9 +/- 0.5 and 4.0 +/- 0.6 au, respectively (P < 0.01). CONCLUSION: The consumption of a greater proportion of energy from protein while dieting may improve sleep in overweight and obese adults. This trial was registered at clinicaltrials.gov as NCT01005563 (study 1) and NCT01692860 (study 2). PMID- 26864363 TI - Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial. AB - BACKGROUND: Chronic inflammation is a central mechanism involved in cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases, 4 leading causes of mortality. Diet is a major source of pro- and anti-inflammatory bioactive compounds. The Dietary Inflammatory Index (DII) was designed to estimate the overall inflammatory potential of the diet. OBJECTIVE: Our aim was to study the prospective association between the DII and mortality, as well as assess whether antioxidant supplementation could modulate this association. DESIGN: The Supplementation en Vitamines et Mineraux Antioxydants study was a randomized, double-blind, placebo-controlled trial in which participants received low-dose antioxidants or a placebo from 1994 to 2002. In this observational prospective analysis, 8089 participants (mean +/- SD age at baseline: 49.0 +/- 6.3 y) were followed between 1994 and 2007 (median: 12.4 y). The DII was calculated from repeated 24-h dietary records; higher scores correspond to more proinflammatory diets. A total of 207 deaths occurred during follow-up, including 123 due to cancer and 41 due to cardiovascular events. Multivariate Cox proportional hazards models were computed. RESULTS: Sex-specific tertiles of the DII were positively associated with cardiovascular + cancer mortality (HR for tertile 3 compared with tertile 1 = 1.53; 95% CI: 1.01, 2.32; P-trend = 0.05) and specific cancer mortality (HR for tertile 3 compared with tertile 1 = 1.83; 95% CI: 1.12, 2.99; P-trend = 0.02). The corresponding P value was 0.07 for all-cause mortality. The DII was statistically significantly associated with increased all cause mortality in the placebo group (HR for tertile 3 compared with tertile 1 = 2.10; 95% CI: 1.15, 3.84; P-trend = 0.02) but not in the antioxidant-supplemented group (P-trend = 0.8; P-interaction = 0.098). CONCLUSION: These results suggest that a proinflammatory diet is associated with increased all-cause and cancer mortality and antioxidants may counteract some of the proinflammatory effects of the diet. This trial was registered at clinicaltrials.gov as NCT00272428. PMID- 26864364 TI - Associations of erythrocyte fatty acid patterns with insulin resistance. AB - BACKGROUND: Synergistic or additive effects or both on cardiometabolic risk may be missed by examining individual fatty acids (FAs). A pattern analysis may be a more useful approach. In addition, it remains unclear whether erythrocyte FA composition relates to insulin resistance among Hispanics/Latinos. OBJECTIVE: We derived erythrocyte FA patterns for a Puerto Rican cohort and examined their association with diet and insulin resistance in cross-sectional and prospective analyses. DESIGN: At baseline, principal components analysis was used to derive factor patterns with the use of 24 erythrocyte FAs from 1157 participants of the Boston Puerto Rican Health Study (aged 45-75 y). Dietary intake was assessed with a validated semiquantitative food-frequency questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated at baseline and at the 2-y follow-up. Relations between FA patterns and HOMA-IR were analyzed in a sample of 922 participants with available data. RESULTS: Five FA patterns were derived, differentiated by 1) relatively high de novo lipogenesis (DNL) FAs and low n-6 (omega-6) FAs, 2) high very-long-chain saturated FAs, 3) high n-3 (omega 3) FAs, 4) high linoleic acid and low arachidonic acid, and 5) high trans FAs. The DNL pattern was positively correlated with sugar and inversely with n-6 and monounsaturated FA intakes. Only the DNL pattern was positively related to baseline HOMA-IR [adjusted geometric means (95% CIs) for quartiles 1 and 4: 1.72 (1.58, 1.87) and 2.20 (2.02, 2.39); P-trend < 0.0001]. Similar associations were observed at 2 y, after adjustment for baseline status [quartiles 1 and 4 means (95% CIs): 1.61 (1.48, 1.76) and 1.84 (1.69, 2.00); P-trend = 0.02]. These results remained consistent after the exclusion of participants with diabetes (n = 485). CONCLUSION: Our findings suggest that upregulated DNL associated with a diet high in sugar and relatively low in unsaturated FAs may adversely affect insulin sensitivity in a Hispanic/Latino cohort. PMID- 26864366 TI - Association of body mass index and survival in pediatric leukemia: a meta analysis. AB - BACKGROUND: Obesity is a worldwide epidemic in children and adolescents. Adult cohort studies have reported an association between higher body mass index (BMI) and increased leukemia-related mortality; whether a similar effect exists in childhood leukemia remains controversial. OBJECTIVE: We conducted a meta-analysis to determine whether a higher BMI at diagnosis of pediatric acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) is associated with worse event free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR). DESIGN: We searched 4 electronic databases from inception through March 2015 without language restriction and included studies in pediatric ALL or AML (0 21 y of age) reporting BMI as a predictor of survival or relapse. Higher BMI, defined as obese (>=95%) or overweight/obese (>=85%), was compared with lower BMI [nonoverweight/obese (<85%)]. Summary risk estimates for EFS, OS, and CIR (ALL only) were calculated with random- or fixed-effects models according to tests for between-study heterogeneity. RESULTS: Of 4690 reports identified, 107 full-text articles were evaluated, with 2 additional articles identified via review of citations; 11 articles were eligible for inclusion in this meta-analysis. In ALL, we observed poorer EFS in children with a higher BMI (RR: 1.35; 95% CI: 1.20, 1.51) than in those at a lower BMI. A higher BMI was associated with significantly increased mortality (RR: 1.31; 95% CI: 1.09, 1.58) and a statistically nonsignificant trend toward greater risk of relapse (RR: 1.17; 95% CI: 0.99, 1.38) compared with a lower BMI. In AML, a higher BMI was significantly associated with poorer EFS and OS (RR: 1.36; 95% CI: 1.16, 1.60 and RR: 1.56; 95% CI: 1.32, 1.86, respectively) than was a lower BMI. CONCLUSION: Higher BMI at diagnosis is associated with poorer survival in children with pediatric ALL or AML. PMID- 26864365 TI - The causal role of breakfast in energy balance and health: a randomized controlled trial in obese adults. AB - BACKGROUND: The causal nature of associations between breakfast and health remain unclear in obese individuals. OBJECTIVE: We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans. DESIGN: The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21-60 y with dual-energy X-ray absorptiometry-derived fat mass indexes of >=13 kg/m(2) for women (n = 15) and >=9 kg/m(2) for men (n = 8). Components of energy balance (resting metabolic rate, physical activity thermogenesis, diet-induced thermogenesis, and energy intake) were measured under free-living conditions with random allocation to daily breakfast (>=700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (e.g., hematology/adipose biopsies). RESULTS: Breakfast resulted in greater physical activity thermogenesis during the morning than when fasting during that period (difference: 188 kcal/d; 95% CI: 40, 335) but without any consistent effect on 24 h physical activity thermogenesis (difference: 272 kcal/d; 95% CI: -254, 798). Energy intake was not significantly greater with breakfast than fasting (difference: 338 kcal/d; 95% CI: -313, 988). Body mass increased across both groups over time but with no treatment effects on body composition or any change in resting metabolic rate (stable within 8 kcal/d). Metabolic/cardiovascular health also did not respond to treatments, except for a reduced insulinemic response to an oral-glucose-tolerance test over time with daily breakfast relative to an increase with daily fasting (P = 0.05). CONCLUSIONS: In obese adults, daily breakfast leads to greater physical activity during the morning, whereas morning fasting results in partial dietary compensation (i.e., greater energy intake) later in the day. There were no differences between groups in weight change and most health outcomes, but insulin sensitivity increased with breakfast relative to fasting. This trial was registered at www.isrctn.org as ISRCTN31521726. PMID- 26864367 TI - Effects of community-based sales of micronutrient powders on morbidity episodes in preschool children in Western Kenya. AB - BACKGROUND: Although the use of micronutrient powders (MNPs) is considered the preferred approach for childhood anemia control, concerns about iron-related morbidity from clinical trials have challenged programmatic scale-up. OBJECTIVE: We aimed to measure the effects of community-based sales of MNPs on diarrhea-, fever-, cough-, and malaria-morbidity episodes in children 6-35 mo of age. DESIGN: We conducted a cluster-randomized trial in rural Western Kenya where 60 villages were randomly assigned to either intervention or control groups. MNPs (containing iron, vitamin A, zinc, and 11 other micronutrients) and other health products (e.g., insecticide-treated bednets, soap, and water disinfectant) were marketed in 30 intervention villages from June 2007 to March 2008. Household visits every 2 wk were used to monitor self-reported MNP use and morbidity (illness episodes in the previous 24 h and hospitalizations in the previous 2 wk) in both groups. Iron, vitamin A, anemia, malaria, and anthropometric measures were assessed at baseline and at 12 mo of follow-up. Data were analyzed by intent to-treat analyses. RESULTS: Of 1062 children enrolled in the study, 1038 children (97.7%) were followed (a total of 14,204 surveillance visits). Mean MNP intake in intervention villages was 0.9 sachets/wk. Children in intervention villages, compared with children in control villages, had ~60% fewer hospitalizations for diarrhea (0.9% compared with 2.4%, respectively; P = 0.03) and 70% fewer hospitalizations for fever (1.8% compared with 5.3%, respectively; P = 0.003) but no significant differences in hospitalizations for respiratory illness (1.1% compared with 2.2%, respectively; P = 0.11) or malaria (3.1% compared with 2.9%, respectively; P = 0.82). There were no differences between groups in the numbers of episodes of diarrhea, cough, or fever. CONCLUSIONS: MNP use in Western Kenya through market-based community sales was not associated with increased infectious morbidity in young children and was associated with decreased hospitalizations for diarrhea and fever. An integrated distribution of MNPs with other health interventions should be explored further in settings with a high child malnutrition and infection burden. This trial was registered at clinicaltrials.gov as NCT01088958. PMID- 26864368 TI - Including whey protein and whey permeate in ready-to-use supplementary food improves recovery rates in children with moderate acute malnutrition: a randomized, double-blind clinical trial. AB - BACKGROUND: The utility of dairy ingredients in the supplementary foods used in the treatment of childhood moderate acute malnutrition (MAM) remains unsettled. OBJECTIVE: We evaluated the effectiveness of a peanut-based ready-to-use supplementary food (RUSF) with soy protein compared with a novel RUSF containing dairy ingredients in the form of whey permeate and whey protein concentrate in the treatment of children with MAM. DESIGN: We conducted a randomized, double blind clinical effectiveness trial involving rural Malawian and Mozambican children 6-59 mo of age with MAM treated with either soy RUSF or a novel whey RUSF treatment of ~75 kcal . kg(-1) . d(-1) for up to 12 wk. RESULTS: The proportion of children that recovered from MAM was significantly higher in the group that received whey RUSF (960 of 1144; 83.9%) than in the group that received soy RUSF (874 of 1086; 80.5%; P < 0.04; risk difference 3.4%, 95% CI: 0.3%, 6.6%). Children who consumed whey RUSF also demonstrated better growth markers, with a higher mean midupper arm circumference (MUAC) at the time of discharge (P < 0.009), greater MUAC gain during the course of treatment (P < 0.003), higher mean weight-for-height z score at discharge (P < 0.008), and greater weight gain (P < 0.05). No significant differences were identified in length gain or time to recovery between the 2 groups. CONCLUSION: This study highlights the importance of milk protein in the treatment of MAM, because the use of a novel whey RUSF resulted in higher recovery rates and improved growth than did soy RUSF, although the whey RUSF supplement provided less total protein and energy than the soy RUSF. This study was registered at clinicaltrials.gov as NCT01790048. PMID- 26864369 TI - Associations of egg and cholesterol intakes with carotid intima-media thickness and risk of incident coronary artery disease according to apolipoprotein E phenotype in men: the Kuopio Ischaemic Heart Disease Risk Factor Study. AB - BACKGROUND: In general populations, the effects of dietary cholesterol on blood cholesterol concentrations are modest. However, the relation is stronger in those with an E4 allele in the apolipoprotein E gene (APOE). There is little information on the association between cholesterol intake and the risk of coronary artery disease (CAD) among those with the ApoE4 phenotype. OBJECTIVE: We investigated the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with carotid intima-media thickness and the risk of incident CAD in middle-aged and older men from eastern Finland. DESIGN: The study included 1032 men aged 42-60 y in 1984-1989 at the baseline examinations of the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Data on common carotid artery intima-media thickness (CCA-IMT) were available for 846 men. Dietary intakes were assessed with 4-d food records. Associations with incident CAD and baseline CCA-IMT were analyzed by using Cox regression and ANCOVA, respectively. RESULTS: The ApoE4 phenotype was found in 32.5% of the men. During the average follow-up of 20.8 y, 230 CAD events occurred. Egg or cholesterol intakes were not associated with the risk of CAD. Each 1 additional egg (55 g)/d was associated with a multivariable-adjusted HR of 1.17 (95% CI: 0.85, 1.61) in the ApoE4 noncarriers and an HR of 0.93 (95% CI: 0.50, 1.72) in the ApoE4 carriers (P-interaction = 0.34). Each 100-mg/d higher cholesterol intake was associated with an HR of 1.04 (95% CI: 0.89, 1.22) in the ApoE4 noncarriers and an HR of 0.95 (95% CI: 0.73, 1.25) in the ApoE4 carriers (P interaction = 0.81). Egg or cholesterol intakes were also not associated with increased CCA-IMT. CONCLUSION: Egg or cholesterol intakes were not associated with increased CAD risk, even in ApoE4 carriers (i.e., in highly susceptible individuals). PMID- 26864370 TI - Dietary energy requirements in relatively healthy maintenance hemodialysis patients estimated from long-term metabolic studies. AB - BACKGROUND: Studies that examined dietary energy requirements (DERs) of patients undergoing maintenance hemodialysis (MHD) have shown mixed results. Many studies reported normal DERs, but some described increased energy needs. DERs in MHD patients have been estimated primarily from indirect calorimetry and from nitrogen balance studies. The present study measured DERs in MHD patients on the basis of their dietary energy intake and changes in body composition. OBJECTIVE: This study assessed DERs in MHD patients who received a constant energy intake while changes in their body composition were measured. DESIGN: Seven male and 6 female sedentary, clinically stable MHD patients received a constant mean (+/-SD) energy intake for 92.2 +/- 7.9 d while residing in a metabolic research ward. Changes in fat and fat-free mass, measured by dual-energy X-ray absorptiometry, were converted to calorie equivalents and added to energy intake to calculate energy requirements. RESULTS: The average DER was 31 +/- 3 kcal . kg(-1) . d(-1) calculated from energy intake and change in fat and fat-free calories, which was 28 +/- 197 kcal/d over the 92 d of the study. DERs of MHD patients correlated strongly with their body weight (r = 0.81, P = 0.002) and less closely with their measured resting energy expenditure expressed as kcal/d (r = 0.69, P = 0.01). Although the average observed DER in MHD patients was similar to published estimated values for normal sedentary individuals of similar age and sex, there was wide variability in DER among individual patients (range: 26-36 kcal . kg(-1) . d(-1)). CONCLUSIONS: Average DERs of sedentary, clinically stable patients receiving MHD are similar to those of sedentary normal individuals. Our data do not support the theory that MHD patients have increased DERs. Due to the high variability in DERs, careful monitoring of the nutritional status of individual MHD patients is essential. This trial was registered at clinicaltrials.gov as NCT02194114. PMID- 26864372 TI - Using citizen science data to identify the sensitivity of species to human land use. AB - Conservation practitioners must contend with an increasing array of threats that affect biodiversity. Citizen scientists can provide timely and expansive information for addressing these threats across large scales, but their data may contain sampling biases. We used randomization procedures to account for possible sampling biases in opportunistically reported citizen science data to identify species' sensitivities to human land use. We analyzed 21,044 records of 143 native reptile and amphibian species reported to the Carolina Herp Atlas from North Carolina and South Carolina between 1 January 1990 and 12 July 2014. Sensitive species significantly associated with natural landscapes were 3.4 times more likely to be legally protected or treated as of conservation concern by state resource agencies than less sensitive species significantly associated with human-dominated landscapes. Many of the species significantly associated with natural landscapes occurred primarily in habitats that had been nearly eradicated or otherwise altered in the Carolinas, including isolated wetlands, longleaf pine savannas, and Appalachian forests. Rare species with few reports were more likely to be associated with natural landscapes and 3.2 times more likely to be legally protected or treated as of conservation concern than species with at least 20 reported occurrences. Our results suggest that opportunistically reported citizen science data can be used to identify sensitive species and that species currently restricted primarily to natural landscapes are likely at greatest risk of decline from future losses of natural habitat. Our approach demonstrates the usefulness of citizen science data in prioritizing conservation and in helping practitioners address species declines and extinctions at large extents. PMID- 26864371 TI - Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children. AB - BACKGROUND: Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. OBJECTIVE: We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. DESIGN: Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for >=30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy , taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. RESULTS: Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. CONCLUSIONS: Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within crossover designs. This trial was registered at clinicaltrials.gov as NCT01411631. PMID- 26864373 TI - C15066. Composition and chemical variability of Ivoirian Polyalthia oliveri leaf oil. AB - The chemical composition of 45 essential oil samples isolated from the leaves of Polyalthia oliveri harvested in three Ivoirian forests was investigated by GC-FID (Retention Indices measured on two columns of different polarities), and by 13 C NMR, following a method developed in our laboratory. In total, 41 components were identified. The content of the main components varied drastically from sample to sample: (E)-beta-caryophyllene (1.2-50.8%), alpha-humulene (0.6-47.7%), isoguaiene (0-27.9%), allo-aromadendrene (0-24.7%), germacrene B (0-18.3%), delta cadinene (0.4-19.3%) and beta-selinene (0.2-18.5%). The analysis of six oil samples selected in function of their chromatographic profiles is reported in detail. The 45 oil compositions were submitted to hierarchical cluster and principal components analysis, which allowed the distinction of three groups within the oil samples. The compositions of the oils from group I (15 samples) and II (12 samples) were dominated by (E)-beta-caryophyllene and alpha-humulene, respectively. Oil samples of group III (18 samples) needed to be partitioned into four sub-groups III.1-III.4 whose compositions were dominated by allo aromadenrene, iso-guaiene, germacrene B and delta-cadinene, respectively. This article is protected by copyright. All rights reserved. PMID- 26864375 TI - Segmental Chromosomal Aberrations in Localized Neuroblastoma Can be Detected in Formalin-Fixed Paraffin-Embedded Tissue Samples and Are Associated With Recurrence. AB - BACKGROUND: Array comparative genomic hybridization (CGH) analyses of frozen tumors have shown strong associations between the pattern of chromosomal aberrations and outcome in patients with advanced-stage neuroblastoma. New platforms for analyzing chromosomal aberrations using formalin-fixed paraffin embedded (FFPE) tissue have recently been developed. We sought to determine whether chromosomal microarray analysis (CMA) using FFPE tumors is feasible and if segmental chromosomal aberrations were prognostic of recurrence in localized neuroblastoma. METHODS: Patients with MYCN nonamplified International Neuroblastoma Staging System stage 1 and 2 disease who recurred were identified. CMA was performed with diagnostic FFPE samples using OncoScanTM FFPE Express 2.0. The prognostic significance of chromosomal pattern was validated in 105 patients with available CGH results. RESULTS: In 26 evaluable patients, 11 recurred locally, nine had metastatic relapse, and six remained progression free >3 years from diagnosis. No chromosomal aberrations were identified in four tumors. Numerical chromosomal aberrations (NCAs) without segmental chromosomal aberration (SCA) were identified in 11 patients: six progressed locally, two had metastatic progression and 3 remained progression-free. Eleven patients had SCAs: four progressed locally, six developed metastatic progression and one remained progression-free. Five or more SCAs were only detected in tumors from patients who developed metastases (P = 0.0004). In the validation cohort, SCAs were associated with inferior event-free survival (EFS) compared to NCA (5-year EFS 68% +/- 8.3% vs. 91% +/- 3.6%, respectively; P = 0.0083). CONCLUSIONS: It is feasible to evaluate chromosomal aberrations using FFPE neuroblastoma tissue. SCA is associated with inferior EFS in localized neuroblastoma patients, and multiple SCAs may be predictive of metastatic relapse. PMID- 26864376 TI - Influence of distal extension of false lumen on adverse aortic events after TEVAR in patients with acute type B aortic dissection. AB - OBJECTIVE: To investigate the clinical outcomes influenced by distal extension of false lumen in acute type B aortic dissection (TBAD) patients following thoracic endovascular aortic repair (TEVAR). METHODS: From April 2002 to January 2013, 264 TBAD patients treated with TEVAR were retrospectively enrolled. The IIIa group exhibited a distal false lumen above the diaphragm (n = 70), and the IIIb group exhibited a distal false lumen under the diaphragm (n = 194). The morphological characteristics and adverse events (30-day and >30 days) were recorded and evaluated. RESULTS: There were no significant differences between the two groups regarding the demographics, comorbidity profiles, or initial feature of computed tomography angiography. The incidence of true lumen compression and branch involvement were significantly increased in the IIIb group compared with the IIIa group (8.6% vs. 25.3%, respectively; 15.7% vs. 36.1%, respectively, both P < 0.05). The 30-day mortality rate was 1.0% (2/194) in the IIIb group, whereas the IIIa group was zero. The incidence of early adverse events, the 5-year cumulative freedom from adverse events, and the 5-year cumulative freedom from all-cause mortality rate were not significantly different between the IIIa and IIIb groups (2.9% vs. 6.7%, 81.4%, and 80.4%, and 95.7% vs. 93.8%, respectively, all P > 0.05). Log-rank tests also indicated there was no significant difference. CONCLUSIONS: There was no significant difference between the IIIa and IIIb groups in the 5-year morality and adverse aortic events following TEVAR. The distal extension of false lumen prior to TEVAR does not influence the long-term morality and adverse aortic events in acute TBAD. PMID- 26864374 TI - Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2-associated Andersen-Tawil Syndrome. AB - KEY POINTS: Xenopus laevis craniofacial development is a good system for the study of Andersen-Tawil Syndrome (ATS)-associated craniofacial anomalies (CFAs) because (1) Kcnj2 is expressed in the nascent face; (2) molecular-genetic and biophysical techniques are available for the study of ion-dependent signalling during craniofacial morphogenesis; (3) as in humans, expression of variant Kcnj2 forms in embryos causes a muscle phenotype; and (4) variant forms of Kcnj2 found in human patients, when injected into frog embryos, cause CFAs in the same cell lineages. Forced expression of WT or variant Kcnj2 changes the normal pattern of Vmem (resting potential) regionalization found in the ectoderm of neurulating embryos, and changes the normal pattern of expression of ten different genetic regulators of craniofacial development, including markers of cranial neural crest and of placodes. Expression of other potassium channels and two different light activated channels, all of which have an effect on Vmem , causes CFAs like those induced by injection of Kcnj2 variants. In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an inactive Cl(-) channel, do not cause CFAs, demonstrating that correct craniofacial development depends on a pattern of bioelectric states, not on ion- or channel-specific signalling. Using optogenetics to control both the location and the timing of ion flux in developing embryos, we show that affecting Vmem of the ectoderm and no other cell layers is sufficient to cause CFAs, but only during early neurula stages. Changes in Vmem induced late in neurulation do not affect craniofacial development. We interpret these data as strong evidence, consistent with our hypothesis, that ATS associated CFAs are caused by the effect of variant Kcnj2 on the Vmem of ectodermal cells of the developing face. We predict that the critical time is early during neurulation, and the critical cells are the ectodermal cranial neural crest and placode lineages. This points to the potential utility of extant, ion flux-modifying drugs as treatments to prevent CFAs associated with channelopathies such as ATS. ABSTRACT: Variants in potassium channel KCNJ2 cause Andersen-Tawil Syndrome (ATS); the induced craniofacial anomalies (CFAs) are entirely unexplained. We show that KCNJ2 is expressed in Xenopus and mouse during the earliest stages of craniofacial development. Misexpression in Xenopus of KCNJ2 carrying ATS-associated mutations causes CFAs in the same structures affected in humans, changes the normal pattern of membrane voltage potential regionalization in the developing face and disrupts expression of important craniofacial patterning genes, revealing the endogenous control of craniofacial patterning by bioelectric cell states. By altering cells' resting potentials using other ion translocators, we show that a change in ectodermal voltage, not tied to a specific protein or ion, is sufficient to cause CFAs. By adapting optogenetics for use in non-neural cells in embryos, we show that developmentally patterned K(+) flux is required for correct regionalization of the resting potentials and for establishment of endogenous early gene expression domains in the anterior ectoderm, and that variants in KCNJ2 disrupt this regionalization, leading to the CFAs seen in ATS patients. PMID- 26864377 TI - Exogenous tannase improves feeding value of a diet containing field beans (Vicia faba) when fed to broilers. AB - A total of 72 male Ross 308 broilers were used in a study to investigate the effect of dietary tannase on apparent metabolisable energy (AME), coefficients of dry matter retention (DMR) and nitrogen retention (NR) and fat digestibility (FD) of a diet containing 300 g/kg field beans (Vicia faba). Growth performance variables and gastrointestinal tract development were also measured. Two treatments were used in this study: control (C) and C + 3400 tannase units (TU) per kg feed. Diets were formulated to be nutritionally adequate with the exception that the AME was lower than recommended (12.65 vs 12.97 MJ/kg, respectively). Inclusion of tannase increased AME by 0.4 MJ/kg DM. Tannase supplementation improved dietary DMR, NR and FD by 2.8%, 3.2% and 6.5%, respectively. Birds given tannase had 4.4% reduction in feed intake and 2.6% improvement in gain to feed ratio (P < 0.05). Compared to control diet, birds given tannase had reduced relative to body weight (%BW) proventriculus and gizzard and pancreas weights, 3.29% vs 3.09% and 0.47% vs 0.44%, respectively. The mechanisms of action of the studied enzyme require further elucidation. PMID- 26864378 TI - Correctors Rescue CFTR Mutations in Nucleotide-Binding Domain 1 (NBD1) by Modulating Proteostasis. AB - We evaluated whether small molecule correctors could rescue four nucleotide binding domain 1 (NBD1) mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (A455E, S492F, DeltaI507, and R560T). We first transfected Cos-7 cells (green monkey kidney cells) with A455E, S492F, DeltaI507, or R560T and created HEK-293 (human embryonic kidney cells) cell lines stably expressing these CFTR mutations. The mutants showed lowered protein expression, instability at physiological temperature, and rapid degradation. After treatment with correctors CFFT-002, CFFT-003, C3, C4, and/or C18, the combination of C18+C4 showed the most correction and resulted in increased CFTR residing in the plasma membrane. We found a profound decrease in binding of CFTR to histone deacetylases (HDAC) 6 and 7 and heat shock proteins (Hsps) 27 and 40. Silencing Hsp27 or 40 rescued the mutants, but no additional amount of CFTR was rescued when both proteins were knocked down simultaneously. Thus, CFTR mutations in NBD1 can be rescued by a combination of correctors, and the treatment alters the interaction between mutated CFTR and the endoplasmic reticulum machinery. PMID- 26864379 TI - The Association Between Postnatal Depression, Acculturation and Mother-Infant Bond Among Eritrean Asylum Seekers in Israel. AB - We examined the association between postnatal depression (PND), acculturation and mother-infant bond among 38 Eritrean asylum seekers in Israel, who were within 6 months of delivery. Participants completed a survey in their native language. A high rate of women (81.6 %) met the clinical threshold for PND on the Edinburgh Postnatal Depression Scale. Higher severity of PND (partial r = -.64, p < .001), higher identification with Israeli culture (partial r = -.45, p = .02), and lower quality of romantic relationship were associated with impaired mother-infant bond (partial r = .58, p = .002). Findings highlight the need to establish services to screen and treat PND among this vulnerable population in the receiving countries. PMID- 26864381 TI - Dry needling for headaches presenting active trigger points. PMID- 26864380 TI - Awareness of Hepatitis C Virus Seropositivity and Chronic Infection in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - Few population-based studies have assessed awareness of hepatitis C virus (HCV) seropositivity and chronic infection. We report awareness of HCV seropositivity and chronic infection and correlates of awareness in a multi-city (Bronx, Miami, Chicago, and San Diego) community-dwelling population sample of United States (US) Hispanics/Latinos recruited during 2008-2011. Included were 260 HCV seropositive participants, among whom 190 had chronic HCV. Among those with chronic HCV, 46 % had been told by a doctor that they had liver disease and 32 % had been told that they had HCV-related liver disease. Among those with chronic HCV who also lacked health insurance (37 % of those with chronic HCV), only 8 % had been told that they had HCV-related liver disease. As compared with the uninsured, those with insurance were over five times more likely to be aware of having HCV-related liver disease (44 %). Sex, age, education, city of residence, and birthplace were not associated with HCV awareness. Less than half of Hispanics/Latinos were aware of their HCV chronic infection. Lack of health insurance may be an important barrier to HCV awareness in this population. PMID- 26864382 TI - Identification of a founder BRCA1 mutation in the Moroccan population. AB - Breast cancer (BC) is the most frequent cancer among women in Morocco. However, the role of the most prevalent BC-predisposing genes, BRCA1 and BRCA2, has been largely unexplored. To help define the role of BRCA1 in BC in Morocco, we characterized the first potential BRCA1 founder mutation in this population. Genetic testing of BRCA1 and BRCA2 in BC high-risk families identified mutation BRCA1 c.5309G>T, p.(Gly1770Val) or G1770V in five independent families from Morocco, suggesting a founder effect. To confirm this hypothesis, haplotype construction was performed using seven intragenic and flanking BRCA1 microsatellite markers. Clinical data were also compiled. Clinical data from carriers of mutation G1770V correspond to data from carriers of BRCA1 pathogenic mutations. Microsatellite analysis showed a common haplotype for the five families in a region comprising 1.54 Mb, confirming G1770V as the first specific founder BRCA1 mutation in the Moroccan population. Our findings contribute to a better understanding of BC genetics in the Moroccan population. Nevertheless, comprehensive studies of mutation G1770V in large series of BC patients from Morocco are needed to assess the real prevalence of this mutation and to improve genetic testing and risk assessment in this population. PMID- 26864383 TI - Discovery of a frameshift mutation in podocalyxin-like (PODXL) gene, coding for a neural adhesion molecule, as causal for autosomal-recessive juvenile Parkinsonism. AB - BACKGROUND: Mutations in known genes for inherited forms of Parkinson's disease (PD) account for <30% of familial PD (FPD) implying that more causal gene(s) remain to be identified. We attempted to discover the putative causal variant in an Indian family with autosomal-recessive juvenile Parkinsonism (ARJP), tested negative for mutations in PARK2, PINK1 and DJ1. METHODS: Whole exomes of two affected siblings were sequenced. Variants prioritised were screened for segregation with disease in the family by targeted sequencing. Gene thus identified was screened for index/additional exonic mutations, if any, in an independent PD cohort by PCR sequencing. Variants observed were functionally validated in differentiated PC12 cells. RESULTS: A novel homozygous frameshift mutation, c.89_90insGTCGCCCC in exon 1 of podocalyxin-like gene (PODXL, 7q32-33), resulting in loss of protein, segregated with disease in the family. Mutant allele was absent in 186 healthy controls screened by PCR sequencing and in control exomes available in the laboratory and public databases. Screening of additional 212 sporadic and 68 FPD cases identified three novel heterozygous missense variants namely c.1285C>A, c.1118G>A and c.881G>A in three unrelated cases. Significant differences in neurite branching and length (p<0.0001) were observed in PC12 cells with wild-type and mutant constructs. CONCLUSIONS: Based on the genetic and functional evidence in this study and literature support on the role of PODXL in neural development, a novel frameshift mutation in PODXL seems to be the likely cause of ARJP in this family. This is the first report suggesting the possible role of a neurodevelopmental pathway in PD aetiology. PMID- 26864384 TI - Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation. AB - The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined (). PMID- 26864386 TI - Comparison of cyclic fatigue resistance between different NiTi instruments with 4% taper. AB - The aim of this study was to make a comparison between the cyclic fatigue (CF) resistance of F360, twisted files (TF), FlexMaster (FM) and RaCE instruments with 4% taper. A total of 40 instruments were evaluated 8 mm from the tip. A stainless steel block with a simulated canal of 1.5 mm diameter, and a 60 degrees angle of curvature was tested using CF testing. One-way ANOVA and posthoc Tukey's test (P < 0.05) were used. The F 360 files showed the highest CF resistance while the TF files had greater CF resistance than the FM and RaCE (P < 0.05). There was no significant difference between the FM and RaCE (P > 0.05). F360 instruments with a double S cross-section had the highest CF resistance among the group. The TF led the NiTi rotary files to be more resistant to fatigue than the FM and RaCE instruments. PMID- 26864385 TI - Nanoscale Metal-Organic Frameworks for Ratiometric Oxygen Sensing in Live Cells. AB - We report the design of a phosphorescence/fluorescence dual-emissive nanoscale metal-organic framework (NMOF), R-UiO, as an intracellular oxygen (O2) sensor. R UiO contains a Pt(II)-porphyrin ligand as an O2-sensitive probe and a Rhodamine-B isothiocyanate ligand as an O2-insensitive reference probe. It exhibits good crystallinity, high stability, and excellent ratiometric luminescence response to O2 partial pressure. In vitro experiments confirmed the applicability of R-UiO as an intracellular O2 biosensor. This work is the first report of a NMOF-based intracellular oxygen sensor and should inspire the design of ratiometric NMOF sensors for other important analytes in biological systems. PMID- 26864387 TI - An updated evolutionary study of Flaviviridae NS3 helicase and NS5 RNA-dependent RNA polymerase reveals novel invariable motifs as potential pharmacological targets. AB - The rate of Flaviviridae family virus infections worldwide has increased dramatically in the last few years. In addition, infections caused by arthropod vector viruses including Hepatitis C, West Nile, Dengue fever, Yellow fever and Japanese encephalitis are emerging throughout the world. Based on a recent taxon update, the Flaviviridae family comprises four main genera; Flavivirus, Hepacivirus, Pestivirus and a recent genus Pegivirus. Although the new scientific classification plays a key role in providing useful information about the relationships between viruses, many new documented viruses remain unclassified. Furthermore, based on the different results of several studies the classification is unclear. In an effort to provide more insights into the classification of viruses, a holistic evolutionary study of the two viral enzymes NS3 helicase and NS5 RNA-dependent RNA polymerase (RdRp) has been conducted in this study. These two viral enzymes are very crucial for the inhibition of viruses due to the fact that they are involved in the survival, proliferation and transmission of viruses. The main goal of this study is the presentation of two novel updated phylogenetic trees of the enzymes NS3 helicase and NS5 RdRp as a reliable phylogeny "map" to correlate the information of the closely related viruses and identify new possible targets for the Flaviviridae family virus inhibition. Despite the earliest trials for drugs against Flaviviridae related viruses, no antiviral drug vaccine has been available to date. Therefore there is an urgent need for research towards the development of efficient antiviral agents. PMID- 26864388 TI - The potential of SNP-based PCR-RFLP capillary electrophoresis analysis to authenticate and detect admixtures of Mediterranean olive oils. AB - Authentication and traceability of extra virgin olive oil is a challenging research task due to the complexity of fraudulent practices. In this context, the monovarietal olive oils of Protected Designation of Origin (PDO) and Protected Geographical Indication (PGI) require new tests and cutting edge analytical technologies to detect mislabeling and misleading origin. Toward this direction, DNA-based technologies could serve as a complementary to the analytical techniques assay. Single nucleotide polymorphisms are ideal molecular markers since they require short PCR analytical targets which are a prerequisite for forensic applications in olive oil sector. In the present study, a small number of polymorphic SNPs were used with an SNP-based PCR-RFLP capillary electrophoresis platform to discriminate six out of 13 monovarietal olive oils of Mediterranean origin from three different countries, Greece, Tunisia, and Lebanon. Moreover, the high sensitivity of capillary electrophoresis in combination with the DNA extraction protocol lowered the limit of detection to 10% in an admixture of Tsounati in a Koroneiki olive oil matrix. PMID- 26864389 TI - Strong plasmon coupling in self-assembled superparamagnetic nanoshell chains. AB - Construction of ordered patterns of plasmonic nanoparticles is greatly important for nanophotonics relevant applications. We have reported a facile and low-cost magnetic field induced self-assembly approach to construct plasmonic superparamagnetic nanoshell (SN) chains up to several hundred micrometers in a few seconds in a large area without templates or other assistance processes. Experimental and theoretical investigations of the near- and far-field optical properties indicate that the super- and sub-radiant modes of the SN chains continuously redshift with the increase of SN number and the Fano resonance emerges in the infinite double- and triple-line SN chains. Strong plasmon coupling effects in the SN chains result in great electric field enhancements at visible and infrared wavelengths, which indicates that these chain structures potentially can be used as a common substrate for both surface enhanced Raman scattering (SERS) and surface-enhanced infrared absorption (SEIRA) application. This fabrication method also offers a general strategy alternative to top-down processing that enables the construction of nanostructures for metamaterials, electromagnetic energy transport, and optical waveguide. PMID- 26864390 TI - Technique of Hill's Gastropexy Combined with Sleeve Gastrectomy for Patients with Morbid Obesity and Gastroesophageal Reflux Disease or Hiatal Hernia. AB - BACKGROUND: Observational studies based on quality-of-life and endoscopy relate sleeve gastrectomy (SG) to gastroesophageal reflux disease (GERD), while some functional studies have demonstrated a decrease in esophageal exposure to gastric acid after SG. Currently, it is recommended to treat hiatal hernia along with the SG. However, as the sleeve gastrectomy involves the resection of the fundus, it is not possible to add a traditional fundoplication to the closure of the hiatus. METHODS: Based on the classic works of Hill et al., and more recent studies by Swanstrom and Aye, our group has incorporated a modified Hill's gastropexy to the sleeve gastrectomy for patients with pathologic GERD and/or huge hiatal hernia submitted to weight loss surgery. RESULTS: A 28-year-old male patient, 43 kg/m(2) BMI, with a small hiatal hernia and pathologic GERD was scheduled for sleeve gastrectomy. After complete fundus and left crus dissection, the phrenoesophageal membrane was opened and the distal esophagus dissected. The hiatus was closed with interrupted sutures. The sleeve was completed over a 42-French bougie. The preaortic fascia was dissected at the root of the crura and three interrupted sutures placed approximating the gastroesophageal junction to the aforementioned fascia. At 6 months from the operation, weight loss has been satisfactory and the patient does not complaint GERD. Barium swallow demonstrates absence of gastroesophageal reflux, pHmetry and manometry have normalized, and endoscopy shows no esophagitis. CONCLUSIONS: Gastropexy to the preaortic fascia is a possible antireflux technique to combine with SG. PMID- 26864391 TI - Fast and accurate Monte Carlo sampling of first-passage times from Wiener diffusion models. AB - We present a new, fast approach for drawing boundary crossing samples from Wiener diffusion models. Diffusion models are widely applied to model choices and reaction times in two-choice decisions. Samples from these models can be used to simulate the choices and reaction times they predict. These samples, in turn, can be utilized to adjust the models' parameters to match observed behavior from humans and other animals. Usually, such samples are drawn by simulating a stochastic differential equation in discrete time steps, which is slow and leads to biases in the reaction time estimates. Our method, instead, facilitates known expressions for first-passage time densities, which results in unbiased, exact samples and a hundred to thousand-fold speed increase in typical situations. In its most basic form it is restricted to diffusion models with symmetric boundaries and non-leaky accumulation, but our approach can be extended to also handle asymmetric boundaries or to approximate leaky accumulation. PMID- 26864392 TI - Rational design and synthesis of a porous, task-specific polycarbazole for efficient CO2 capture. AB - We present a rational design and synthesis of a novel porous pyridine functionalized polycarbazole for efficient CO2 capture based on the density functional theory calculations. The task-specific polymer, generated through a one-step FeCl3-catalyzed oxidative coupling reaction, exhibits a superior CO2 uptake at 1.0 bar and 273 K (5.57 mmol g(-1)). PMID- 26864393 TI - Sequentially Different AB Diblock and ABA Triblock Copolymers as P3HT:PCBM Interfacial Compatibilizers for Bulk-Heterojunction Photovoltaics. AB - The P3HT:PCBM (P3HT = poly(3-hexylthiophene, PCBM = phenyl-C61-butyric acid methyl ester) bulk-heterojunction (BHJ) organic photovoltaic (OPV) cells using the AB diblock and ABA triblock copolymers (A = polystyrene derivative with donor acceptor units (PTCNE) and B = P3HT) as compatibilizers were fabricated. Under the optimized blend ratio of the block copolymer, the power conversion efficiency (PCE) was enhanced. This PCE enhancement was clearly related to the increased short-circuit current (J(sc)) and fill factor (FF). The incident photon to current efficiency (IPCE) measurement suggested that the P3HT crystallinity was improved upon addition of the block copolymers. The increased P3HT crystallinity was consistent with the increased photovoltaic parameters, such as J(sc), FF, and consequently the PCE. The surface energies of these block copolymers suggested their thermodynamically stable location at the interface of P3HT:PCBM, showing the efficient compatibilizing performance, resulting in enlarging and fixing the interfacial area and suppressing the recombination of the generated carriers. Grazing incidence X-ray scattering (GIXS) results confirmed the superior compatibilizing performance of the ABA triblock copolymer when compared to the AB diblock copolymer by the fact that, after blending the ABA triblock copolymer in the P3HT:PCBM system, the enhanced crystallinity of matrix P3HT was observed in the excluded areas of the less-aggregated PCBM domains, changing the P3HT crystalline domain orientation from "edge-on" to "isotropic". This is, to the best of our knowledge, the first sequential effect (AB vs ABA) of the block copolymers on the compatibilizing performances based on BHJ OPV device systems. PMID- 26864394 TI - The one-pot multienzyme (OPME) synthesis of human blood group H antigens and a human milk oligosaccharide (HMOS) with highly active Thermosynechococcus elongates alpha1-2-fucosyltransferase. AB - A novel alpha1-2-fucosyltransferase from Thermosynechococcus elongatus BP-1 (Te2FT) with high fucosyltransferase activity and low donor hydrolysis activity was discovered and characterized. It was used in an efficient one-pot multienzyme (OPME) fucosylation system for the high-yield synthesis of human blood group H antigens containing beta1-3-linked galactosides and an important human milk oligosaccharide (HMOS) lacto-N-fucopentaose I (LNFP I) on preparative and gram scales. LNFP I was shown to be selectively consumed by Bifidobacterium longum subsp. infantis but not Bifidobacterium animalis subsp. lactis and is a potential prebiotic. PMID- 26864399 TI - Moon: Yoshida Hodaka. PMID- 26864396 TI - Insertable cardiac monitors in the diagnosis of syncope and the detection of atrial fibrillation: A systematic review and meta-analysis. AB - BACKGROUND: Insertable or implantable cardiac monitors (ICMs) continuously monitor the heart rhythm and record irregularities over 3 years, enabling the diagnosis of infrequent rhythm abnormalities associated with syncope and stroke. The enhanced recognition capabilities of recent ICM models are able to accurately detect atrial fibrillation (AF) and have led to new applications of ICMs for the detection and monitoring of AF. METHODS AND RESULTS: Based on a systematic literature search, two indications were identified for ICMs for which considerable evidence, including randomized studies, exists: diagnosing the underlying cardiac cause of unexplained recurrent syncope and detecting AF in patients after cryptogenic stroke (CS). Three randomized controlled trials (RCTs) were identified that compared the effectiveness of ICMs in diagnosing patients with unexplained syncope (n = 556) to standard of care. A meta-analysis was conducted in order to generate an overall effect size and confidence interval of the diagnostic yield of ICMs versus conventional monitoring. In the indication CS, one RCT and five observational studies were included in order to assess the performance of ICMs in diagnosing patients with AF (n = 1129). Based on these studies, there is strong evidence that ICMs provide a higher diagnostic yield for detecting arrhythmias in patients with unexplained syncope and for detection of AF in patients after CS compared to conventional monitoring. CONCLUSIONS: Prolonged monitoring with ICMs is an effective tool for diagnosing the underlying cardiac cause of unexplained syncope and for detecting AF in patients with CS. In all RCTs, ICMs have a superior diagnostic yield compared to conventional monitoring. PMID- 26864395 TI - Association of Patient Age at Gastric Bypass Surgery With Long-term All-Cause and Cause-Specific Mortality. AB - IMPORTANCE: Bariatric surgery is effective in reducing all-cause and cause specific long-term mortality. Whether the long-term mortality benefit of surgery applies to all ages at which surgery is performed is not known. OBJECTIVE: To examine whether gastric bypass surgery is equally effective in reducing mortality in groups undergoing surgery at different ages. DESIGN, SETTING, AND PARTICIPANTS: All-cause and cause-specific mortality rates and hazard ratios (HRs) were estimated from a retrospective cohort within 4 categories defined by age at surgery: younger than 35 years, 35 through 44 years, 45 through 54 years, and 55 through 74 years. Mean follow-up was 7.2 years. Patients undergoing gastric bypass surgery seen at a private surgical practice from January 1, 1984, through December 31, 2002, were studied. Data analysis was performed from June 12, 2013, to September 6, 2015. A cohort of 7925 patients undergoing gastric bypass surgery and 7925 group-matched, severely obese individuals who did not undergo surgery were identified through driver license records. Matching criteria included year of surgery to year of driver license application, sex, 5-year age groups, and 3 body mass index categories. INTERVENTION: Roux-en-Y gastric bypass surgery. MAIN OUTCOMES AND MEASURES: All-cause and cause-specific mortality compared between those undergoing and not undergoing gastric bypass surgery using HRs. RESULTS: Among the 7925 patients who underwent gastric bypass surgery, the mean (SD) age at surgery was 39.5 (10.5) years, and the mean (SD) presurgical body mass index was 45.3 (7.4). Compared with 7925 matched individuals not undergoing surgery, adjusted all-cause mortality after gastric bypass surgery was significantly lower for patients 35 through 44 years old (HR, 0.54; 95% CI, 0.38 0.77), 45 through 54 years old (HR, 0.43; 95% CI, 0.30-0.62), and 55 through 74 years old (HR, 0.50; 95% CI, 0.31-0.79; P < .003 for all) but was not lower for those younger than 35 years (HR, 1.22; 95% CI, 0.82-1.81; P = .34). The lack of mortality benefit in those undergoing gastric bypass surgery at ages younger than 35 years primarily derived from a significantly higher number of externally caused deaths (HR, 2.53; 95% CI, 1.27-5.07; P = .009), particularly among women (HR, 3.08; 95% CI, 1.4-6.7; P = .005). Patients undergoing gastric bypass surgery had a significantly lower age-related increase in mortality than severely obese individuals not undergoing surgery (P = .001). CONCLUSIONS AND RELEVANCE: Gastric bypass surgery was associated with improved long-term survival for all patients undergoing surgery at ages older than 35 years, with externally caused deaths only elevated in younger women. Gastric bypass surgery is protective against mortality even for older patients and also reduces the age-related increase in mortality observed in severely obese individuals not undergoing surgery. PMID- 26864406 TI - Machine Learning and the Profession of Medicine. PMID- 26864407 TI - A PIECE OF MY MIND. Can I Eat Yet? PMID- 26864408 TI - Improving Outpatient Antibiotic Prescribing: Another Nudge in the Right Direction. PMID- 26864409 TI - Learning From the Past to Improve VA Health Care. PMID- 26864410 TI - Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing Among Primary Care Practices: A Randomized Clinical Trial. AB - IMPORTANCE: Interventions based on behavioral science might reduce inappropriate antibiotic prescribing. OBJECTIVE: To assess effects of behavioral interventions and rates of inappropriate (not guideline-concordant) antibiotic prescribing during ambulatory visits for acute respiratory tract infections. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized clinical trial conducted among 47 primary care practices in Boston and Los Angeles. Participants were 248 enrolled clinicians randomized to receive 0, 1, 2, or 3 interventions for 18 months. All clinicians received education on antibiotic prescribing guidelines on enrollment. Interventions began between November 1, 2011, and October 1, 2012. Follow-up for the latest-starting sites ended on April 1, 2014. Adult patients with comorbidities and concomitant infections were excluded. INTERVENTIONS: Three behavioral interventions, implemented alone or in combination: suggested alternatives presented electronic order sets suggesting nonantibiotic treatments; accountable justification prompted clinicians to enter free-text justifications for prescribing antibiotics into patients' electronic health records; peer comparison sent emails to clinicians that compared their antibiotic prescribing rates with those of "top performers" (those with the lowest inappropriate prescribing rates). MAIN OUTCOMES AND MEASURES: Antibiotic prescribing rates for visits with antibiotic-inappropriate diagnoses (nonspecific upper respiratory tract infections, acute bronchitis, and influenza) from 18 months preintervention to 18 months afterward, adjusting each intervention's effects for co-occurring interventions and preintervention trends, with random effects for practices and clinicians. RESULTS: There were 14,753 visits (mean patient age, 47 years; 69% women) for antibiotic-inappropriate acute respiratory tract infections during the baseline period and 16,959 visits (mean patient age, 48 years; 67% women) during the intervention period. Mean antibiotic prescribing rates decreased from 24.1% at intervention start to 13.1% at intervention month 18 (absolute difference, 11.0%) for control practices; from 22.1% to 6.1% (absolute difference, -16.0%) for suggested alternatives (difference in differences, -5.0% [95% CI, -7.8% to 0.1%]; P = .66 for differences in trajectories); from 23.2% to 5.2% (absolute difference, -18.1%) for accountable justification (difference in differences, 7.0% [95% CI, -9.1% to -2.9%]; P < .001); and from 19.9% to 3.7% (absolute difference, -16.3%) for peer comparison (difference in differences, -5.2% [95% CI, -6.9% to -1.6%]; P < .001). There were no statistically significant interactions (neither synergy nor interference) between interventions. CONCLUSIONS AND RELEVANCE: Among primary care practices, the use of accountable justification and peer comparison as behavioral interventions resulted in lower rates of inappropriate antibiotic prescribing for acute respiratory tract infections. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01454947. PMID- 26864412 TI - Association of Admission to Veterans Affairs Hospitals vs Non-Veterans Affairs Hospitals With Mortality and Readmission Rates Among Older Men Hospitalized With Acute Myocardial Infarction, Heart Failure, or Pneumonia. AB - IMPORTANCE: Little contemporary information is available about comparative performance between Veterans Affairs (VA) and non-VA hospitals, particularly related to mortality and readmission rates, 2 important outcomes of care. OBJECTIVE: To assess and compare mortality and readmission rates among men in VA and non-VA hospitals. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis involving male Medicare fee-for-service beneficiaries aged 65 years or older hospitalized between 2010 and 2013 in VA and non-VA acute care hospitals for acute myocardial infarction (AMI), heart failure (HF), or pneumonia using the Medicare Standard Analytic Files and Enrollment Database together with VA administrative claims data. To avoid confounding geographic effects with health care system effects, we studied VA and non-VA hospitals within the same metropolitan statistical area (MSA). EXPOSURES: Hospitalization in a VA or non-VA hospital in MSAs that contained at least 1 VA and non-VA hospital. MAIN OUTCOMES AND MEASURES: For each condition, 30-day risk-standardized mortality rates and risk-standardized readmission rates for VA and non-VA hospitals. Mean aggregated within-MSA differences in mortality and readmission rates were also assessed. RESULTS: We studied 104 VA and 1513 non-VA hospitals, with each condition-outcome analysis cohort for VA and non-VA hospitals containing at least 7900 patients (men; >=65 years), in 92 MSAs. Mortality rates were lower in VA hospitals than non-VA hospitals for AMI (13.5% vs 13.7%, P = .02; -0.2 percentage-point difference) and HF (11.4% vs 11.9%, P = .008; -0.5 percentage-point difference), but higher for pneumonia (12.6% vs 12.2%, P = .045; 0.4 percentage-point difference). In contrast, readmission rates were higher in VA hospitals for all 3 conditions (AMI, 17.8% vs 17.2%, 0.6 percentage-point difference; HF, 24.7% vs 23.5%, 1.2 percentage-point difference; pneumonia, 19.4% vs 18.7%, 0.7 percentage point difference, all P < .001). In within-MSA comparisons, VA hospitals had lower mortality rates for AMI (percentage-point difference, -0.22; 95% CI, -0.40 to -0.04) and HF (-0.63; 95% CI, -0.95 to -0.31), and mortality rates for pneumonia were not significantly different (-0.03; 95% CI, -0.46 to 0.40); however, VA hospitals had higher readmission rates for AMI (0.62; 95% CI, 0.48 to 0.75), HF (0.97; 95% CI, 0.59 to 1.34), or pneumonia (0.66; 95% CI, 0.41 to 0.91). CONCLUSIONS AND RELEVANCE: Among older men with AMI, HF, or pneumonia, hospitalization at VA hospitals, compared with hospitalization at non-VA hospitals, was associated with lower 30-day risk-standardized all-cause mortality rates for AMI and HF, and higher 30-day risk-standardized all-cause readmission rates for all 3 conditions, both nationally and within similar geographic areas, although absolute differences between these outcomes at VA and non-VA hospitals were small. PMID- 26864413 TI - Antibiotic Therapy for Adults Hospitalized With Community-Acquired Pneumonia: A Systematic Review. AB - IMPORTANCE: Antibiotic therapy is the cornerstone of medical management for community-acquired pneumonia. OBJECTIVE: To assess the associations between 3 key aspects of antibiotic therapy (optimal time to antibiotic initiation, initial antibiotic selection, and criteria for the transition from intravenous to oral therapy) and short-term mortality in adults hospitalized with community-acquired pneumonia. EVIDENCE REVIEW: Bibliographic databases of MEDLINE, EMBASE, and the Cochrane Collaboration were searched for studies of adults hospitalized with radiographically confirmed community-acquired pneumonia published from January 1, 1995, until November 5, 2015. FINDINGS: Twenty studies (17 observational and 3 randomized trials) met eligibility criteria. Among 8 observational studies identified, the 4 largest (study populations of 2878 to 1,170,022) found that antibiotic initiation within 4 to 8 hours of hospital arrival was associated with relative reductions of 5% to 43% in mortality; the 4 smallest studies (study populations of 451 to 2076) found no associations between the timing of antibiotic initiation and mortality. One cluster randomized trial (n = 1737) demonstrated noninferiority of beta-lactam monotherapy (n = 506) vs beta-lactam plus macrolide combination therapy (n = 566), with an absolute adjusted difference of 2.5% (90% CI, -0.6% to 5.2%) in 90-day mortality favoring beta lactam monotherapy. A second randomized trial (n = 580) failed to demonstrate noninferiority of beta-lactam monotherapy vs beta-lactam plus macrolide combination therapy, with an absolute difference of 7.6% (1-sided 90% CI upper limit, 13.0%) in attainment of clinical stability on hospital day 7 favoring beta lactam plus macrolide combination therapy. Six of 8 observational studies (study populations of 1188 to 24,780) found that beta-lactam plus macrolide combination therapy was associated with relative reductions of 26% to 68% in short-term mortality and all 3 observational studies (study populations of 2068 to 24,780) reported that fluoroquinolone monotherapy was associated with relative reductions of 30% to 43% in mortality compared with beta-lactam monotherapy. One randomized trial (n = 302) reported significantly reduced hospital length of stay (absolute difference, 1.9 days; 95% CI, 0.6 to 3.2 days), but no differences in treatment failure when objective clinical criteria were used to decide when to transition patients from intravenous to oral therapy. CONCLUSIONS AND RELEVANCE: In adults hospitalized with community-acquired pneumonia, antibiotic therapy consisting of beta-lactam plus macrolide combination therapy or fluoroquinolone monotherapy initiated within 4 to 8 hours of hospital arrival was associated with lower adjusted short-term mortality, supported predominantly by low-quality observational studies. One randomized trial supports the use of objective clinical criteria to guide the transition from intravenous to oral antibiotic therapy. PMID- 26864414 TI - Changing the "Working While Sick" Culture: Promoting Fitness for Duty in Health Care. PMID- 26864415 TI - HbA1c in the Evaluation of Diabetes Mellitus. PMID- 26864411 TI - Effect of a Task-Oriented Rehabilitation Program on Upper Extremity Recovery Following Motor Stroke: The ICARE Randomized Clinical Trial. AB - IMPORTANCE: Clinical trials suggest that higher doses of task-oriented training are superior to current clinical practice for patients with stroke with upper extremity motor deficits. OBJECTIVE: To compare the efficacy of a structured, task-oriented motor training program vs usual and customary occupational therapy (UCC) during stroke rehabilitation. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, pragmatic, single-blind randomized trial among 361 participants with moderate motor impairment recruited from 7 US hospitals over 44 months, treated in the outpatient setting from June 2009 to March 2014. INTERVENTIONS: Structured, task oriented upper extremity training (Accelerated Skill Acquisition Program [ASAP]; n = 119); dose-equivalent occupational therapy (DEUCC; n = 120); or monitoring only occupational therapy (UCC; n = 122). The DEUCC group was prescribed 30 one hour sessions over 10 weeks; the UCC group was only monitored, without specification of dose. MAIN OUTCOMES AND MEASURES: The primary outcome was 12 month change in log-transformed Wolf Motor Function Test time score (WMFT, consisting of a mean of 15 timed arm movements and hand dexterity tasks). Secondary outcomes were change in WMFT time score (minimal clinically important difference [MCID] = 19 seconds) and proportion of patients improving >=25 points on the Stroke Impact Scale (SIS) hand function score (MCID = 17.8 points). RESULTS: Among the 361 randomized patients (mean age, 60.7 years; 56% men; 42% African American; mean time since stroke onset, 46 days), 304 (84%) completed the 12-month primary outcome assessment; in intention-to-treat analysis, mean group change scores (log WMFT, baseline to 12 months) were, for the ASAP group, 2.2 to 1.4 (difference, 0.82); DEUCC group, 2.0 to 1.2 (difference, 0.84); and UCC group, 2.1 to 1.4 (difference, 0.75), with no significant between-group differences (ASAP vs DEUCC: 0.14; 95% CI, -0.05 to 0.33; P = .16; ASAP vs UCC: 0.01; 95% CI, -0.22 to 0.21; P = .94; and DEUCC vs UCC: -0.14; 95% CI, -0.32 to 0.05; P = .15). Secondary outcomes for the ASAP group were WMFT change score, 8.8 seconds, and improved SIS, 73%; DEUCC group, WMFT, -8.1 seconds, and SIS, 72%; and UCC group, WMFT, -7.2 seconds, and SIS, 69%, with no significant pairwise between-group differences (ASAP vs DEUCC: WMFT, 1.8 seconds; 95% CI, 0.8 to 4.5 seconds; P = .18; improved SIS, 1%; 95% CI, -12% to 13%; P = .54; ASAP vs UCC: WMFT, -0.6 seconds, 95% CI, -3.8 to 2.6 seconds; P = .72; improved SIS, 4%; 95% CI, -9% to 16%; P = .48; and DEUCC vs UCC: WMFT, -2.1 seconds; 95% CI, 4.5 to 0.3 seconds; P = .08; improved SIS, 3%; 95% CI, -9% to 15%; P = .22). A total of 168 serious adverse events occurred in 109 participants, resulting in 8 patients withdrawing from the study. CONCLUSIONS AND RELEVANCE: Among patients with motor stroke and primarily moderate upper extremity impairment, use of a structured, task-oriented rehabilitation program did not significantly improve motor function or recovery beyond either an equivalent or a lower dose of UCC upper extremity rehabilitation. These findings do not support superiority of this program among patients with motor stroke and primarily moderate upper extremity impairment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00871715. PMID- 26864416 TI - Major Causes of Injury Death and the Life Expectancy Gap Between the United States and Other High-Income Countries. PMID- 26864417 TI - Blood Pressure Control and Recurrence of Intracerebral Hemorrhage. PMID- 26864418 TI - Blood Pressure Control and Recurrence of Intracerebral Hemorrhage--Reply. PMID- 26864419 TI - Value of Personalized Medicine. PMID- 26864420 TI - Value of Personalized Medicine. PMID- 26864421 TI - Value of Personalized Medicine--Reply. PMID- 26864423 TI - Misstated Terminology. PMID- 26864425 TI - The Highlands of Medicine. PMID- 26864426 TI - JAMA PATIENT PAGE. Pneumonia. PMID- 26864427 TI - Keratinizing desquamative squamous metaplasia in the kidney of a patient with complex spinal cord injury. AB - CONTEXT: Keratinizing desquamative squamous metaplasia (KDSM) of the upper urinary tract was previously thought, but never proven, to represent a premalignant condition. However, no clear guidelines exist regarding the long term management and follow up once this rare diagnosis has been made. FINDINGS: Patients with spinal cord injury often develop a range of risk factors for malignancy of the urinary tract. We present the first reported case of KDSM in the kidney of a 44-year-old man with spinal cord injury whose complex urological history includes previous augmentation cystoplasty, recurrent calculi, infections and indwelling catheters. CLINICAL RELEVANCE: Recent literature has suggested a move away from the previous mainstay of treatment with radical surgery towards nephron-sparing endoscopic and radiological surveillance. This case highlights the complexity of preserving renal function in a spinal cord injured patient with KDSM of the kidney. PMID- 26864428 TI - Microbially assisted recording of the Earth's magnetic field in sediment. AB - Sediments continuously record variations of the Earth's magnetic field and thus provide an important archive for studying the geodynamo. The recording process occurs as magnetic grains partially align with the geomagnetic field during and after sediment deposition, generating a depositional remanent magnetization (DRM) or post-DRM (PDRM). (P)DRM acquisition mechanisms have been investigated for over 50 years, yet many aspects remain unclear. A key issue concerns the controversial role of bioturbation, that is, the mechanical disturbance of sediment by benthic organisms, during PDRM acquisition. A recent theory on bioturbation-driven PDRM appears to solve many inconsistencies between laboratory experiments and palaeomagnetic records, yet it lacks experimental proof. Here we fill this gap by documenting the important role of bioturbation-induced rotational diffusion for (P)DRM acquisition, including the control exerted on the recorded inclination and intensity, as determined by the equilibrium between aligning and perturbing torques acting on magnetic particles. PMID- 26864430 TI - Hirschsprung disease with debut in adult age as acute intestinal obstruction: case report. AB - Hirschsprung's disease is characterized by absence of ganglion cells in submucosal and myenteric plexus of distal bowel. Most cases become manifest during the neonatal period, but in rare instances, this disease is initially diagnosed in adult age. It usually presents as severe constipation with colonic dilatation proximal to the aganglionic segment. The treatment is surgical, removing the aganglionic segment and restoring continuity of digestive tract. The disease rarely presents as an acute intestinal obstruction. We report a case not previously diagnosed, which presented as a massive colonic dilatation with a maximum diameter of 44 cm, with imminent risk of drilling that forced to perform an emergency surgery. We include a review of existing literature. PMID- 26864429 TI - Microbial communities affecting albumen photography heritage: a methodological survey. AB - This study is one of the few investigations which analyze albumen prints, perhaps the most important photographic heritage of the late 19(th) and early 20(th) centuries. The chemical composition of photographic samples was assessed using Fourier-transform infrared spectroscopy and X-ray fluorescence. These two non invasive techniques revealed the complex nature of albumen prints, which are composed of a mixture of proteins, cellulose and salts. Microbial sampling was performed using cellulose nitrate membranes which also permitted the trapped microflora to be observed with a scanning electron microscope. Microbial analysis was performed using the combination of culture-dependent (cultivation in different media, including one 3% NaCl) and culture-independent (bacterial and fungal cloning and sequencing) approaches. The isolated microorganisms were screened for their lipolytic, proteolytic, cellulolytic, catalase and peroxidase activities. The combination of the culture-dependent and -independent techniques together with enzymatic assays revealed a substantial microbial diversity with several deteriogen microorganisms from the genera Bacillus, Kocuria, Streptomyces and Geobacillus and the fungal strains Acrostalagmus luteoalbus, Bjerkandera adusta, Pleurotus pulmonarius and Trichothecium roseum. PMID- 26864431 TI - Staying in Shape: the Impact of Cell Shape on Bacterial Survival in Diverse Environments. AB - Bacteria display an abundance of cellular forms and can change shape during their life cycle. Many plausible models regarding the functional significance of cell morphology have emerged. A greater understanding of the genetic programs underpinning morphological variation in diverse bacterial groups, combined with assays of bacteria under conditions that mimic their varied natural environments, from flowing freshwater streams to diverse human body sites, provides new opportunities to probe the functional significance of cell shape. Here we explore shape diversity among bacteria, at the levels of cell geometry, size, and surface appendages (both placement and number), as it relates to survival in diverse environments. Cell shape in most bacteria is determined by the cell wall. A major challenge in this field has been deconvoluting the effects of differences in the chemical properties of the cell wall and the resulting cell shape perturbations on observed fitness changes. Still, such studies have begun to reveal the selective pressures that drive the diverse forms (or cell wall compositions) observed in mammalian pathogens and bacteria more generally, including efficient adherence to biotic and abiotic surfaces, survival under low-nutrient or stressful conditions, evasion of mammalian complement deposition, efficient dispersal through mucous barriers and tissues, and efficient nutrient acquisition. PMID- 26864434 TI - High-resolution isotope measurements resolve rapid ecohydrological dynamics at the soil-plant interface. AB - Plants rely primarily on rainfall infiltrating their root zones - a supply that is inherently variable, and fluctuations are predicted to increase on most of the Earth's surface. Yet, interrelationships between water availability and plant use on short timescales are difficult to quantify and remain poorly understood. To overcome previous methodological limitations, we coupled high-resolution in situ observations of stable isotopes in soil and transpiration water. We applied the approach along with Bayesian mixing modeling to track the fate of (2) H-labeled rain pulses following drought through soil and plants of deciduous tree ecosystems. We resolve how rainwater infiltrates the root zones in a nonequilibrium process and show that tree species differ in their ability to quickly acquire the newly available source. Sessile oak (Quercus petraea) adjusted root uptake to vertical water availability patterns under drought, but readjustment toward the rewetted topsoil was delayed. By contrast, European beech (Fagus sylvatica) readily utilized water from all soil depths independent of water depletion, enabling faster uptake of rainwater. Our results demonstrate that species-specific plasticity and responses to water supply fluctuations on short timescales can now be identified and must be considered to predict vegetation functional dynamics and water cycling under current and future climatic conditions. PMID- 26864433 TI - Mammalian cells lacking either the cotranslational or posttranslocational oligosaccharyltransferase complex display substrate-dependent defects in asparagine linked glycosylation. AB - Asparagine linked glycosylation of proteins is an essential protein modification reaction in most eukaryotic organisms. Metazoan organisms express two oligosaccharyltransferase complexes that are composed of a catalytic subunit (STT3A or STT3B) assembled with a shared set of accessory subunits and one to two complex specific subunits. siRNA mediated knockdowns of STT3A and STT3B in HeLa cells have shown that the two OST complexes have partially non-overlapping roles in N-linked glycosylation. However, incomplete siRNA mediated depletion of STT3A or STT3B reduces the impact of OST complex loss, thereby complicating the interpretation of experimental results. Here, we have used the CRISPR/Cas9 gene editing technology to create viable HEK293 derived cells lines that are deficient for a single catalytic subunit (STT3A or STT3B) or two STT3B-specific accessory subunits (MagT1 and TUSC3). Analysis of protein glycosylation in the STT3A, STT3B and MagT1/TUSC3 null cell lines revealed that these cell lines are superior tools for investigating the in vivo role and substrate preferences of the STT3A and STT3B complexes. PMID- 26864437 TI - Asymmetric, Three-Component, One-Pot Synthesis of Spiropyrazolones and 2,5 Chromenediones from Aldol Condensation/NHC-Catalyzed Annulation Reactions. AB - A novel one-pot, three-component diastereo- and enantioselective synthesis of spiropyrazolones has been developed involving the aldol condensation of an enal to generate alpha,beta-unsaturated pyrazolones, which react with a second equivalent of enal through an N-heterocyclic carbene (NHC)-catalyzed [3+2] annulation. The desired spirocyclopentane pyrazolones are obtained in moderate to good yields and good to excellent stereoselectivities. Alternatively, starting from cyclic 1,3-diketones, 2,5-chromenediones are available through [2+4] annulation. PMID- 26864436 TI - Decoration of intramyocellular lipid droplets with PLIN5 modulates fasting induced insulin resistance and lipotoxicity in humans. AB - AIMS/HYPOTHESIS: In contrast to insulin-resistant individuals, insulin-sensitive athletes possess high intramyocellular lipid content (IMCL), good mitochondrial function and high perilipin 5 (PLIN5) levels, suggesting a role for PLIN5 in benign IMCL storage. We hypothesised a role for PLIN5 in modulating fasting mediated insulin resistance. METHODS: Twelve men were fasted for 60 h, before and after which muscle biopsies were taken and stained for lipid droplets (LDs), PLIN5 and laminin. Confocal microscopy images were analysed for LD size, number, PLIN5 association and subcellular distribution. RESULTS: Fasting elevated IMCL content 2.8-fold and reduced insulin sensitivity (by 55%). Individuals with the most prominent increase in IMCL showed the least reduction in insulin sensitivity (r = 0.657; p = 0.028) and mitochondrial function (r = 0.896; p = 0.006). During fasting, PLIN5 gene expression or PLIN5 protein content in muscle homogenates was unaffected, microscopy analyses revealed that the fraction of PLIN5 associated with LDs (PLIN5+) increased significantly (+26%) upon fasting, suggesting PLIN5 redistribution. The significant increase in LD number (+23%) and size (+23%) upon fasting was entirely accounted for by PLIN5+ LDs, not by LDs devoid of PLIN5. Also the association between IMCL storage capacity and insulin resistance and mitochondrial dysfunction was only apparent for PLIN5+ LDs. CONCLUSIONS/INTERPRETATION: Fasting results in subcellular redistribution of PLIN5 and promotes the capacity to store excess fat in larger and more numerous PLIN5-decorated LDs. This associates with blunting of fasting-induced insulin resistance and mitochondrial dysfunction, suggesting a role for PLIN5 in the modulation of fasting-mediated lipotoxicity. TRIAL REGISTRATION: trialregister.nl NTR 2042. PMID- 26864438 TI - Knowledge and Attitudes About Oral Cancer Among Dental Students After Bologna Plan Implementation. AB - Oral cancer is the most common of head and neck tumours. Dentists have an important role in the most effective prevention measures: controlling aetiological factors and early detection. Dental curriculum has suffered changes in their structures and contents during Bologna process. The aim of this study is to explore oral cancer knowledge and attitudes among dental students of Granada after the implementation of the Bologna plan. A cross-sectional study was carried out in the School of Dentistry of the University of Granada. A questionnaire was delivered to dental students in the fourth and fifth years (of study) to assess knowledge and attitudes about oral cancer area. 79.3 % related that they examined the oral mucosa from their patients regularly. Almost the whole sample (95.9 %) said that they would advise their patients about risk factors for oral cancer when they graduated. Tobacco followed by alcohol was the main oral cancer risk factor identified (94.2 and 72.7 %, respectively). 96.7 % of the sample would like to receive more information about this subject. Fourth year students had taught self-examination for early detection of oral cancer more frequently than fifth year students (42.5 versus 22.9 %, respectively). The results of this study revealed that dental students had good attitudes in the area of oral cancer. On the other hand, it highlights the need for an improvement of the teaching program regarding risk factors for oral cancer and performing routine oral examination. PMID- 26864439 TI - Quality of life in functional rhinoplasty: rhinoplasty outcomes evaluation German version (ROE-D). AB - The aim of this study was to validate a German version of the rhinoplasty outcomes evaluation (ROE) questionnaire. A prospective study was conducted and a German translated ROE (ROE-D) questionnaire administered to 100 patients preoperatively, 6 and 12 months postoperatively. The translation was performed according to internationally accepted guidelines. To validate this instrument, we evaluated its reliability, validity and sensitivity. ROE-D was completed by 54 patients after 6 months and by 69 patients 1 year after functional rhinoplasty. Cronbach's alpha indicated good internal consistency. Reliability was tested with a split-half-reliability, showing significant correlation. Discrimination validity was demonstrated by a comparison with healthy controls. Sensitivity to change showed medium to large effects. ROE-D is a reliable, validated and sensitive German instrument for measuring health-related quality of life in patients after rhinoplasty. The ROE-D focuses mainly on the aesthetic aspects of the rhinoplasty surgery. PMID- 26864441 TI - Male Breast Cancer Has Limited Effect on Survivor's Perceptions of Their Own Masculinity. AB - The purpose of the current study was to describe male breast cancer in Johannesburg, South Africa, and assess whether male breast cancer patients' perception of their own masculinity was affected by having a cancer commonly seen in women. A retrospective file review was carried out at two hospitals, one private and one government, of male breast cancer patients from 2007 to 2012 followed by a telephone survey of patients identified during review. Of approximately 3,000 breast cancer patients seen in the 5 years reviewed, 23 cases of male breast cancer were identified. Most were diagnosed with invasive ductal carcinoma ( n = 19, 83%). Stage at presentation was from stages 0 to 3 (Stage 0 [ n = 2, 9%], Stage 1 [ n = 3, 13%], Stage 2 [ n = 12, 52%], Stage 3 [ n = 6, 26%]) and no patients were metastatic at presentation. The telephonic survey was completed by 18 patients (78%). Nearly all ( n = 17/18) shared their diagnosis with family and close friends. Two thirds of patients delayed presentation and government hospital patients were more likely to present later than private sector hospital patients. Although most male breast cancer patients sampled did not perceive the breast cancer diagnosis as affecting their masculinity, Black men and those treated in government hospitals were less likely to be aware of male breast cancer, and were more likely to have their perception of their own masculinity affected. PMID- 26864440 TI - Reviewing the Assumptions About Men's Mental Health: An Exploration of the Gender Binary. AB - Many researchers take for granted that men's mental health can be explained in the same terms as women's or can be gauged using the same measures. Women tend to have higher rates of internalizing disorders (i.e., depression, anxiety), while men experience more externalizing symptoms (i.e., violence, substance abuse). These patterns are often attributed to gender differences in socialization (including the acquisition of expectations associated with traditional gender roles), help seeking, coping, and socioeconomic status. However, measurement bias (inadequate survey assessment of men's experiences) and clinician bias (practitioner's subconscious tendency to overlook male distress) may lead to underestimates of the prevalence of depression and anxiety among men. Continuing to focus on gender differences in mental health may obscure significant within gender group differences in men's symptomatology. In order to better understand men's lived experiences and their psychological well-being, it is crucial for scholars to focus exclusively on men's mental health. PMID- 26864442 TI - Myristoylation increases the CD8+T-cell response to a GFP prototype antigen delivered by modified vaccinia virus Ankara. AB - Activation of CD8(+)T-cells is an essential part of immune responses elicited by recombinant modified vaccinia virus Ankara (MVA). Strategies to enhance T-cell responses to antigens may be particularly necessary for broadly protective immunization against influenza A virus infections or for candidate vaccines targeting chronic infections and cancer. Here, we tested recombinant MVAs that targeted a model antigen, GFP, to different localizations in infected cells. In vitro characterization demonstrated that GFP accumulated in the nucleus (MVA-nls GFP), associated with cellular membranes (MVA-myr-GFP) or was equally distributed throughout the cell (MVA-GFP). On vaccination, we found significantly higher levels of GFP-specific CD8(+)T-cells in MVA-myr-GFP-vaccinated BALB/c mice than in those immunized with MVA-GFP or MVA-nls-GFP. Thus, myristoyl modification may be a useful strategy to enhance CD8(+)T-cell responses to MVA-delivered target antigens. PMID- 26864443 TI - Oxidative elemental cycling under the low O2 Eoarchean atmosphere. AB - The Great Oxidation Event signals the first large-scale oxygenation of the atmosphere roughly 2.4 Gyr ago. Geochemical signals diagnostic of oxidative weathering, however, extend as far back as 3.3-2.9 Gyr ago. 3.8-3.7 Gyr old rocks from Isua, Greenland stand as a deep time outpost, recording information on Earth's earliest surface chemistry and the low oxygen primordial biosphere. Here we find fractionated Cr isotopes, relative to the igneous silicate Earth reservoir, in metamorphosed banded iron formations (BIFs) from Isua that indicate oxidative Cr cycling 3.8-3.7 Gyr ago. Elevated U/Th ratios in these BIFs relative to the contemporary crust, also signal oxidative mobilization of U. We suggest that reactive oxygen species were present in the Eoarchean surface environment, under a very low oxygen atmosphere, inducing oxidative elemental cycling during the deposition of the Isua BIFs and possibly supporting early aerobic biology. PMID- 26864444 TI - Editorial: Endothelium: A Target for Therapeutic Intervention. PMID- 26864445 TI - Editorial: Vascular Calcification, Cardiovascular Risk and microRNAs. AB - Vascular calcification, both in the coronary and in the peripheral arteries, is associated with increased cardiovascular (CV) risk. However, agents that prevent vascular calcification (e.g. estrogens or calcimimetic agents) might have neutral or detrimental effects on CV events. Moreover, statins and antihypertensive agents do not appear to modify vascular calcification, despite their established benefits on CV disease prevention. On the other hand, recent data suggest that microRNAs play a role in the regulation of vascular calcification. It is therefore possible that modulation of the expression of microRNAs might represent a useful strategy for preventing or delaying the progression of this process. PMID- 26864446 TI - Supramolecular Organization of Dye Molecules in Zeolite L Channels: Synthesis, Properties, and Composite Materials. AB - Sequential insertion of different dyes into the 1D channels of zeolite L (ZL) leads to supramolecular sandwich structures and allows the formation of sophisticated antenna composites for light harvesting, transport, and trapping. The synthesis and properties of dye molecules, host materials, composites, and composites embedded in polymer matrices, including two- and three-color antenna systems, are described. Perylene diimide (PDI) dyes are an important class of chromophores and are of great interest for the synthesis of artificial antenna systems. They are especially well suited to advancing our understanding of the structure-transport relationship in ZL because their core fits tightly through the 12-ring channel opening. The substituents at both ends of the PDIs can be varied to a large extent without influencing their electronic absorption and fluorescence spectra. The intercalation/insertion of 17 PDIs, 2 terrylenes, and 1 quaterrylene into ZL are compared and their interactions with the inner surface of the ZL nanochannels discussed. ZL crystals of about 500 nm in size have been used because they meet the criteria that must be respected for the preparation of antenna composites for light harvesting, transport, and trapping. The photostability of dyes is considerably improved by inserting them into the ZL channels because the guests are protected by being confined. Plugging the channel entrances, so that the guests cannot escape into the environment is a prerequisite for achieving long-term stability of composites embedded in an organic matrix. Successful methods to achieve this goal are described. Finally, the embedding of dye-ZL composites in polymer matrices, while maintaining optical transparency, is reported. These results facilitate the rational design of advanced dye-zeolite composite materials and provide powerful tools for further developing and understanding artificial antenna systems, which are among the most fascinating subjects of current photochemistry and photophysics. PMID- 26864447 TI - Dynamic Histone Acetylation of H3K4me3 Nucleosome Regulates MCL1 Pre-mRNA Splicing. AB - Pre-mRNA splicing is a cotranscriptional process affected by the chromatin architecture along the body of coding genes. Recruited to the pre-mRNA by splicing factors, histone deacetylases (HDACs) and K-acetyltransferases (KATs) catalyze dynamic histone acetylation along the gene. In colon carcinoma HCT 116 cells, HDAC inhibition specifically increased KAT2B occupancy as well as H3 and H4 acetylation of the H3K4 trimethylated (H3K4me3) nucleosome positioned over alternative exon 2 of the MCL1 gene, an event paralleled with the exclusion of exon 2. These results were reproduced in MDA-MB-231, but not in MCF7 breast adenocarcinoma cells. These later cells have much higher levels of demethylase KDM5B than either HCT 116 or MDA-MB-231 cells. We show that H3K4me3 steady-state levels and H3K4me3 occupancy at the end of exon 1 and over exon 2 of the MCL1 gene were lower in MCF7 than in MDA-MB-231 cells. Furthermore, in MCF7 cells, there was minimal effect of HDAC inhibition on H3/H4 acetylation and H3K4me3 levels along the MCL1 gene and no change in pre-mRNA splicing choice. These results show that, upon HDAC inhibition, the H3K4me3 mark plays a critical role in the exclusion of exon 2 from the MCL1 pre-mRNA. J. Cell. Physiol. 231: 2196 2204, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864449 TI - Metabolic disruption identified in the Huntington's disease transgenic sheep model. AB - Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease. PMID- 26864451 TI - Changing trends in the incidence of juvenile nasopharyngeal angiofibroma: seven decades of experience at King George's Medical University, Lucknow, India. AB - BACKGROUND: The occurrence of juvenile nasopharyngeal angiofibroma is reportedly higher in India than in some other parts of the world, and our centre has seen a four-fold increase in its occurrence across seven decades. METHODS: This paper reports a retrospective archival analysis of 701 juvenile nasopharyngeal angiofibroma cases from 1958 to 2013, and considers probable environmental factors in an Indian context that may affect its biology and the global distribution, as reported in the literature. RESULTS: A continuously progressive increase in occurrence was evident, but the rapid rise observed in the current decade was alarming. The world map of juvenile nasopharyngeal angiofibroma incidence does not reflect true global distribution given the paucity of reporting. Our centre has dealt with approximately 400 cases in the last 24 years. CONCLUSION: With the alarming increase in juvenile nasopharyngeal angiofibroma incidence, there is a need for a registry to define its epidemiology. The world literature needs to reflect the status of juvenile nasopharyngeal angiofibroma incidence in the third world as well. Environmental factors known for hormone disruptive actions may influence its occurrence. Such aspects need to be considered to plan specific prevention policies. PMID- 26864450 TI - Transgenic mice recapitulate the phenotypic heterogeneity of genetic prion diseases without developing prion infectivity: Role of intracellular PrP retention in neurotoxicity. AB - Genetic prion diseases are degenerative brain disorders caused by mutations in the gene encoding the prion protein (PrP). Different PrP mutations cause different diseases, including Creutzfeldt-Jakob disease (CJD), Gerstmann Straussler-Scheinker (GSS) syndrome and fatal familial insomnia (FFI). The reason for this variability is not known. It has been suggested that prion strains with unique self-replicating and neurotoxic properties emerge spontaneously in individuals carrying PrP mutations, dictating the phenotypic expression of disease. We generated transgenic mice expressing the FFI mutation, and found that they developed a fatal neurological illness highly reminiscent of FFI, and different from those of similarly generated mice modeling genetic CJD and GSS. Thus transgenic mice recapitulate the phenotypic differences seen in humans. The mutant PrPs expressed in these mice are misfolded but unable to self-replicate. They accumulate in different compartments of the neuronal secretory pathway, impairing the membrane delivery of ion channels essential for neuronal function. Our results indicate that conversion of mutant PrP into an infectious isoform is not required for pathogenesis, and suggest that the phenotypic variability may be due to different effects of mutant PrP on intracellular transport. PMID- 26864452 TI - Structuring successful collaboration: a longitudinal social network analysis of a translational research network. AB - BACKGROUND: In 2012 and 2013, we conducted a social network survey of a new translational research network (TRN) designed to deliver better care to cancer patients. Results of these two surveys showed that silos of researchers and clinicians existed before the TRN was established but that the network had mediated collaborative relationships. This paper reports on a third social network survey of the TRN and focusses on the structure of the collaborative arrangements among members. METHODS: Members of the TRN were invited to complete an on-line, whole network survey in May 2015. The survey asked respondents to identify personal impacts, outputs and wider outcomes attributable to their TRN membership. The final question asked respondents to select the name of TRN members with whom they had collaborated either formally or informally. For each member nominated, they were asked to say whether they had known this person before joining the TRN. RESULTS: Response rate was 70 %. Over 4 years, the TRN has grown in size from 68 to 244 members. Relationships within and across the TRN have become more collaborative and interactive, with 1658 collaborative ties between members and over 40 % of ties with people unknown to participants before they joined the TRN. This points to a well-functioning network which has retained its focus on the original goals of the TRN and has fostered collaboration between researchers, clinicians, managers, consumers and TRN operational staff. This survey shows that the TRN's impact goes beyond outcomes from formal TRN-funded projects. About one third of respondents could list projects not directly funded by the TRN but which are attributed to TRN membership. Examples of practice change brought about through the TRN were given by 77 % of respondents. A substantial risk factor for the future is the high levels of dependency on key or central TRN participants. CONCLUSIONS: The structure of the TRN with its active central actors and brokers has been able to foster collaboration on implementation initiatives that result in practice change. The role of a social professional network in driving this collaboration is shown. PMID- 26864453 TI - A diversity of peri-implant mucosal thickness by site. AB - OBJECTIVES: The objective of this study was to examine peri-implant mucosal thickness at different sites of peri-implant crevice around 70 implants placed in 35 patients. MATERIAL AND METHODS: The peri-implant mucosal thickness was defined as distance of the peri-implant mucosal margin and the coronal edge of bone/implant contact and measured using the cast models and dental radiography. RESULTS: The overall mean peri-implant mucosal thickness was 3.6 +/- 1.4 mm, wherein maxillary anterior implants, maxillary posterior implants and mandibular posterior implants had significantly different dimensions of median thickness of 4.25, 3.75 and 3.0 mm, respectively. Furthermore, the mesial and distal sites of those positioned implants measured unevenness in the thickness especially in the maxillary posterior region with statistical significance. CONCLUSION: The proposed methodology to evaluate peri-implant mucosal thickness measured with a big variation from overall 3.6 mm with a big variation from 1.6 to 7.0 mm in healthy volunteers. And significant difference was found in the depth among the three regions and, statistically, dispersion of individual peri-implant mucosal thickness resulted in lack of consistency. Although dental implants have been well developed, predictable and prevailing prosthetics, onset of peri-implantitis might be inevitable in some cases. Therefore, establishment of a standardized dimensional diagnosis of peri-implant tissues followed by pathologic ascertainment could be taken into account for the prevention or curing of peri implantitis. PMID- 26864454 TI - Prevalence and course of sexual relationship difficulties in recovered and non recovered patients with borderline personality disorder over 16 years of prospective follow-up. AB - Although borderline patients experience a wide range of sexual problems, including promiscuity, there is less evidence documenting their sexual relationship difficulties. This study had two aims. The first was to examine the prevalence of these difficulties (i.e. avoidance of sex and being symptomatic after sex) over 16 years of prospective follow-up among recovered and non recovered patients with borderline personality disorder (BPD). The second was to determine time-to-remission, recurrence and new onset of these sexual relationship difficulties. The sexual relationship difficulties of 290 patients meeting both DIB-R and DSM-III-R criteria for BPD were assessed at baseline using the Abuse History Interview and reassessed every two years over eight waves of prospective follow-up. The prevalence of sexual relationship difficulties declined significantly over time for both groups of patients, while remaining significantly more common among non-recovered patients. By 16-year follow-up, over 95% of each group achieved remission for both types of difficulties. Recurrences of avoidance of sex were significantly more common in non-recovered patients. Non-recovered patients had higher rates of new onsets compared to recovered patients for each type of sexual relationship difficulty. Taken together, the results suggest that sexual relationship difficulties are not chronic for those with BPD regardless of recovery status. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864455 TI - Current Experimental Methods for Characterizing Protein-Protein Interactions. AB - Protein molecules often interact with other partner protein molecules in order to execute their vital functions in living organisms. Characterization of protein protein interactions thus plays a central role in understanding the molecular mechanism of relevant protein molecules, elucidating the cellular processes and pathways relevant to health or disease for drug discovery, and charting large scale interaction networks in systems biology research. A whole spectrum of methods, based on biophysical, biochemical, or genetic principles, have been developed to detect the time, space, and functional relevance of protein-protein interactions at various degrees of affinity and specificity. This article presents an overview of these experimental methods, outlining the principles, strengths and limitations, and recent developments of each type of method. PMID- 26864456 TI - Efficacy of oseltamivir-peramivir combination therapy compared to oseltamivir monotherapy for Influenza A (H7N9) infection: a retrospective study. AB - BACKGROUND: Since the novel H7N9 avian influenza outbreak occurred in China in 2013, neuraminidase inhibitors (NAIs) such as oseltamivir and peramivir have been used as first-line drugs to treat the influenza virus infection. This study aimed to compare the efficacy of oseltamivir-peramivir combination therapy versus oseltamivir monotherapy. METHODS: A retrospective study of 82 H7N9 confirmed patients was conducted by reviewing medical charts at the First Affiliated Hospital of ZheJiang University in China from April 1, 2013 to Feb 28, 2014. The patients' clinical information was collected systematically, and we compared the virology and clinical data between oseltamivir monotherapy group (43 patients) and oseltamivir-peramivir combination group (39 patients). RESULTS: The median duration from NAIs administration to H7N9 virus-negative in oseltamivir monotherapy group and oseltamivir-peramivir combination group was 6.50 and 7.00 days (p >0.05), respectively. The median decline of Day 2 to Day 0 (initiation of NAIs therapy) viral load was 0.00 and 0.69 log10 copies/MUl (p >0.05) respectively in the monotherapy vs. combination therapy groups. The incidence of new Acute Respiratory Distress Syndrome during NAI administration was 63.89 and 77.78 % (p >0.05); while the mortality rates were 25.58 and 43.59 % (p >0.05) in the oseltamivir group vs. oseltamivir-peramivir group. CONCLUSIONS: Our results suggest that in adults with H7N9 virus infection, the use of oseltamivir peramivir combination therapy was not superior to oseltamivir monotherapy. PMID- 26864457 TI - Comorbidities and inpatient mortality for pemphigus in the U.S.A. AB - BACKGROUND: The morbidity and mortality associated with pemphigus and its treatments have not been fully described. Previous studies have found conflicting results about certain comorbidities and were limited by small sample sizes. OBJECTIVES: To determine the morbidity and mortality from pemphigus and its treatments in the U.S.A. METHODS: We examined a cross-sectional cohort of 87 039 711 hospitalized patients in the U.S.A. to determine the inpatient comorbidities and mortality of pemphigus. RESULTS: In multivariate survey logistic regression models adjusting for age, sex and race/ethnicity, pemphigus and its treatments were associated with 39 of 122 comorbidities examined. The disorders most strongly associated with pemphigus were Cushing syndrome [adjusted odds ratio (OR) 17.23, 95% confidence interval (CI) 2.41-122.90], adrenal insufficiency (4.08, 1.71-9.73), myasthenia gravis (6.92, 2.55-18.79), mucositis (17.19, 7.73 38.22), herpes infection (7.98, 3.62-17.62), fungal infections (4.03, 3.60-4.52), insomnia (18.02, 2.46-131.88) and hidradenitis (5.34, 1.33-21.43). Among malignancies, only leukaemia (OR 1.56, 95% CI 1.08-2.24) and non-Hodgkin lymphoma (1.52, 1.15-2.03) were associated with pemphigus, but not any solid organ malignancies. Patients with a secondary diagnosis of pemphigus had higher inpatient mortality (3.20%, 95% CI 2.71-3.69) than those with a primary (1.60%, 1.29-1.91) or no (1.78%, 1.78-1.78) diagnosis of pemphigus (P < 0.001). CONCLUSIONS: Pemphigus is associated with increased inpatient mortality, likely through its association with numerous comorbid health conditions. Patients with pemphigus require improved access to dermatological care and increased screening for the myriad of comorbidities. PMID- 26864458 TI - The Impact of Echocardiographic Epicardial Fat Thickness on Outcomes of Cryoballoon-Based Atrial Fibrillation Ablation. AB - BACKGROUND: Evidence from previous studies indicates increased epicardial fat volume, measured using computerized tomography, is significantly associated with recurrence of atrial fibrillation (AF) after catheter ablation. This association is most frequently linked to pro-inflammatory cytokine release from epicardial fat tissue. However, there is little data regarding the role of echocardiographically measured epicardial fat thickness (EFT) on catheter ablation outcomes. We aimed to investigate the predictive value of echocardiographically measured EFT on AF recurrence after cryoballoon-based catheter ablation. METHODS: A total of 234 patients (51.3% male; mean age, 54.0 +/- 10.9 years; 81.2% paroxysmal AF) with symptomatic AF underwent an initial cryoablation procedure. EFT was measured from the parasternal long-axis view at end-systole. A 3-month postablation blanking period was observed. RESULTS: At a median follow-up of 20 (IQR: 13-24) months, 45 patients (19.2%) had developed AF recurrence. EFT thickness was significantly higher among patients with AF recurrence (7.79 +/- 2.0 vs. 5.79 +/- 1.38, P < 0.001) and was positively correlated with hs-CRP levels (r = 0.381, P < 0.001). Multivariate regression analysis showed EFT (HR: 1.36, 95% CI: 1.10-1.66, P = 0.004), left atrial diameter, and early AF recurrence were independent predictors of AF recurrence. Using a cutoff level of 6.92, preprocedural EFT predicted AF recurrence during follow-up with a sensitivity of 71.1% and specificity of 78.3% (AUC: 0.79; 95% CI: 0.71-0.87, P < 0.001). CONCLUSION: Echocardiographically measured EFT independently predicted the AF recurrence after cryoablation and was also positively correlated with hs-CRP as an indicator for systemic inflammation. Thus, the association of echocardiographically measured EFT with AF recurrence may be linked to systemic inflammation. PMID- 26864459 TI - Mild cold effects on hunger, food intake, satiety and skin temperature in humans. AB - BACKGROUND: Mild cold exposure increases energy expenditure and can influence energy balance, but at the same time it does not increase appetite and energy intake. OBJECTIVE: To quantify dermal insulative cold response, we assessed thermal comfort and skin temperatures changes by infrared thermography. METHODS: We exposed healthy volunteers to either a single episode of environmental mild cold or thermoneutrality. We measured hunger sensation and actual free food intake. After a thermoneutral overnight stay, five males and five females were exposed to either 18 degrees C (mild cold) or 24 degrees C (thermoneutrality) for 2.5 h. Metabolic rate, vital signs, skin temperature, blood biochemistry, cold and hunger scores were measured at baseline and for every 30 min during the temperature intervention. This was followed by an ad libitum meal to obtain the actual desired energy intake after cold exposure. RESULTS: We could replicate the cold-induced increase in REE. But no differences were detected in hunger, food intake, or satiety after mild cold exposure compared with thermoneutrality. After long-term cold exposure, high cold sensation scores were reported, which were negatively correlated with thermogenesis. Skin temperature in the sternal area was tightly correlated with the increase in energy expenditure. CONCLUSIONS: It is concluded that short-term mild cold exposure increases energy expenditure without changes in food intake. Mild cold exposure resulted in significant thermal discomfort, which was negatively correlated with the increase in energy expenditure. Moreover, there is a great between-subject variability in cold response. These data provide further insights on cold exposure as an anti-obesity measure. PMID- 26864460 TI - Evaluation of anti-inflammatory activity and standardisation of hydro-methanol extract of underground tuber of Dioscorea alata. AB - Context The underground edible tuber of Dioscorea alata L. (Dioscoreaceae) is a functional food with high nutritive value and therapeutic potential. The tuber is known to possess anti-inflammatory properties in traditional medicine. Objective The present study explores the anti-inflammatory activity and standardisation of D. alata tuber hydromethanol extract. Materials and methods Hydromethanol extract (70%) of D. alata tuber was chemically characterised using HPLC and GC-MS techniques. Murine lymphocytes were cultured for 48 h with six different concentrations (0-80 MUg/mL) of the extract. The expression of nitric oxide (NO), TNF-alpha, COX-1, COX-2, and PGE2 were evaluated using colorimetric and ELISA methods. Results Dioscorea alata extract inhibited the expression of NO and TNF alpha with an IC50 value of 134.51 +/- 6.75 and 113.30 +/- 7.44 MUg/mL, respectively. The IC50 values for inhibition of total COX, COX-1, COX-2 activities and PGE2 level were 41.96 +/- 3.07, 141.41 +/- 8.99, 32.50 +/- 1.69, and 186.34 +/- 15.36 MUg/mL, respectively. Inhibition of PGE2 level and COX-2 activity was positively correlated (R(2) = 0.9393). Gallic acid (GA), 4-hydroxy benzoic acid (4HBA), syringic acid (SYA), p-coumaric acid (PCA), and myricetin (MY) were identified and quantified using HPLC. GC-MS analysis revealed the presence of 13 different phytocompounds such as hexadecanoic acid, methyl stearate, cinnamyl cinnamate, and squalene. Conclusion The D. alata extract significantly down-regulated the pro-inflammatory signals in a gradual manner compared with control (0 MUg/mL). Different bioactive phytocompounds individually possessing anti-inflammatory activities contributed to the overall bioactivity of the D. alata tuber extract. PMID- 26864461 TI - Malaria in children of Tshimbulu (Western Kasai, Democratic Republic of the Congo): epidemiological data and accuracy of diagnostic assays applied in a limited resource setting. AB - BACKGROUND: The literature data on malaria in Western Kasai, DRC, are limited and inadequate. A recent molecular survey there has detected Plasmodium ovale and Plasmodium malariae as mixed infections with Plasmodium falciparum. In Tshimbulu, Western Kasai, during a humanitarian initiative designed to provide children with free preventive screening and to reduce the local high malaria death rate, accurate species identification was performed, in order to collect unambiguous epidemiological data and to evaluate the reliability of locally applied diagnostics. METHODS: Finger pricks provided fresh blood for microscopic analysis (MA), for rapid diagnostic test (RDT) and for molecular diagnostics (MD). MA and RDT were first performed by the local team and then a re-interpretation of the results (on the same slides and on RDT's taken pictures) was conducted in Italy, where MD were performed. RESULTS: The analysis was conducted on 306 children; RDT found 80.9 % as P. falciparum-positive (37.4 % as two-band positive, P. falciparum single infection). MA identified a further four children as positive to P. falciparum and six co-infections with P. ovale. The second RDT evaluation confirmed a similar infection rate (78.2 %) but interpreted as two-band positive a significantly higher share of tests (56.8 %). MA confirmed 80.0 % of the children as malaria positive and, in addition to P. falciparum, identified P. malariae (13.8 %), P. vivax (3.4 %) and P. ovale (2.4 %), and detected Babesia microti in 19 smears. MD confirmed all of the species found (Babesia microti included), classified as mono-infection with P. falciparum a rate of spots comparable to MA revision, and identified all P. ovale as Plasmodium ovale wallikeri. The RDT used locally proved 93.1 % sensitive and 92.1 % specific for P. falciparum. CONCLUSIONS: The malaria prevalence among the children and the presence of four Plasmodium species, highlighted in this study, identified a sanitary issue which proved to be more alarming than expected, as it was worsened by the unpredictable presence of P. vivax and Babesia microti (never before reported in DRC). Each diagnostic tool showed its point of weakness. Therefore, the most correct approach is by the combined use of different, locally available, diagnostic tools. PMID- 26864462 TI - Separation of three phenolic high-molecular-weight compounds from the crude extract of Terminalia Chebula Retz. by ultrasound-assisted extraction and high speed counter-current chromatography. AB - This study presents an efficient strategy for separation of three phenolic compounds with high molecular weight from the crude extract of Terminalia chebula Retz. by ultrasound-assisted extraction and high-speed counter-current chromatography. The ultrasound-assisted extraction conditions were optimized by response surface methodology and the results showed the target compounds could be well enriched under the optimized extraction conditions. Then the crude extract was directly separated by high-speed counter-current chromatography without any pretreatment using n-hexane/ethyl acetate/methanol/water (1:7:0.5:3, v/v/v/v) as the solvent system. In 180 min, 13 mg of A, 18 mg of B, and 9 mg of C were obtained from 200 mg of crude sample. Their structures were identified as Chebulagic acid (A, 954 Da), Chebulinic acid (B, 956 Da), and Ellagic acid (C) by (1) H NMR spectroscopy. PMID- 26864463 TI - The Timing of Breast Irradiation in Two-Stage Expander/Implant Breast Reconstruction. AB - Certain patients who initiate expander/implant (E/I) reconstruction following mastectomy may require radiation therapy (XRT). XRT may be delivered during the tissue expander (TE) expansion process or after exchange for a permanent implant (PI). We studied a series of women treated with E/I reconstruction and XRT to determine whether there is a difference in complication rates between those who had XRT to the TE versus PI. All two-stage E/I reconstructions at our institution from April 2005 to January 2013 were reviewed to identify patients who underwent XRT after TE placement. Our database was queried for reconstructive details, oncologic treatment, and complications. Statistical analyses were performed to establish significance of complication rate differences. Fifty-two patients underwent XRT after TE placement, 42 of which had XRT to the TE and 11 of which had XRT to the PI. The major complication rates (complications requiring emergent reoperation/readmission) were 27% versus 0% (p = 0.05) for XRT to the TE versus XRT to the PI, but there were no significant differences in minor complication rates (outpatient complications). Specifically, the rates of Grade 3/4 capsular contracture were similar between the two groups, 27% for the XRT to the TE group and 36% for the XRT to the PI group. Radiation of the PI versus radiation of the TE did not result in significant differences in overall surgical complication rates but had fewer major complications and no implant failures. Other factors must also be considered, such as patient preference, risk of cancer reoccurrence, and cosmesis. It is essential for a patient to have a team of a plastic surgeon and radiation, surgical, and medical oncologists working together to achieve each patient's goals. PMID- 26864464 TI - Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy. AB - BACKGROUND: Paradoxical inflammations during anti-TNF-alpha therapy are defined as adverse effects such as psoriasiform skin lesions, uveitis and sarcoidosis like granulomas induced by immune reactions, not by infectious agents. Here, we report a very rare case of the simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy and both of which resolved spontaneously without the cessation of infliximab. CASE PRESENTATION: In September 2000, 23-year old Japanese male was diagnosed with Crohn's disease. Prednisolone in combination with mesalazine was introduced at first and succeeded for almost one year. In June 2002, since his gastrointestinal symptoms relapsed and were refractory, infliximab (IFX) therapy 5 mg/kg was introduced. In February 2011, because he had repeated arthralgia almost every intravenous IFX administration, IFX was increased to 10 mg/kg under the diagnosis of a secondary failure of IFX. In December 2012, he complained of slight dry cough and an itchy eruption on both lower limbs, and he was referred to our hospital due to the appearance of bilateral hilar lymphadenopathy on chest X-ray examination. Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. Serum calcium, angiotensin-converting enzyme and soluble interleukin 2 receptor levels were not elevated, but the titer of antinuclear antibody was considerably elevated. Mycobacterium infection was carefully excluded. Trans bronchial lung biopsy showed non-caseating epithelioid cell granulomas compatible with sarcoidosis. The skin biopsy of the right limb was diagnosed as leukocytoclastic vasculitis. The patient was diagnosed as having a series of paradoxical inflammations during anti-TNF-alpha therapy. Since his paradoxical inflammations were not severe and opportunistic infections were excluded, IFX was cautiously continued for refractory Crohn's disease. Nine months later, not only his intrathoracic lesions but also his cutaneous lesions had spontaneously resolved. CONCLUSION: Physicians caring for patients with anti-TNF-alpha therapy should know that, based on a careful exclusion of infectious agents and thoughtful assessment of the patient's possible risks and benefits, paradoxical inflammations can be resolved without the cessation of anti-TNF-alpha therapy. PMID- 26864465 TI - Allopatric divergence of Stuckenia filiformis (Potamogetonaceae) on the Qinghai Tibet Plateau and its comparative phylogeography with S. pectinata in China. AB - In the aquatic genus Stuckenia, the wide geographic range of S. pectinata and S. filiformis make them suited for examination of topographic and climatic effects on plant evolution. Using nuclear ITS sequence and ten chloroplast sequences, we conducted comparative phylogeographical analyses to investigate their distribution regions and hybrid zones in China, and compare their phylogeographical patterns and demographical histories. These two species were allopatric in China. S. filiformis occurred only on the Qinghai-Tibet Plateau (QTP), whereas S. pectinata occupied a wide range of habitats. These two species formed hybrid zones on the northeastern edge of QTP. Most of the genetic variance of S. filiformis was between the southern and eastern groups on the QTP, showing a significant phylogeographic structure. The geographical isolations caused by the Nyenchen Tanglha Mountains and the Tanggula Mountains promoted intraspecific diversification of alpine plants on the QTP. This study revealed the lack of phylogeographic structure in S. pectinata, due to the continued gene flow among its distribution regions. The ecological niche modeling showed that the distribution ranges of these two herbaceous species did not contract too much during the glacial period. PMID- 26864466 TI - In vivo knockdown of basal forebrain p75 neurotrophin receptor stimulates choline acetyltransferase activity in the mature hippocampus. AB - This study seeks to determine whether knockdown of basal forebrain p75 neurotrophin receptor (p75(NTR) ) expression elicits increased hippocampal choline acetyltransferase (ChAT) activity in mature animals. Antisense (AS) oligonucleotides (oligos) targeting p75(NTR) were infused into the medial septal area of mature rats continuously for 4 weeks. In all rats, the cannula outlet was placed equidistant between the left and the right sides of the vertical diagonal band of Broca. We tested phosphorothioate (PS), morpholino (Mo), and gapmer (mixed PS/RNA) oligos. Gapmer AS infusions of 7.5 and 22 MUg/day decreased septal p75(NTR) mRNA by 34% and 48%, respectively. The same infusions increased hippocampal ChAT activity by 41% and 55%. Increased hippocampal ChAT activity correlated strongly with septal p75(NTR) downregulation in individual rats. Infusions of PS and Mo AS oligos did not downregulate p75(NTR) mRNA or stimulate ChAT activity. These results demonstrate that p75(NTR) can dynamically regulate hippocampal ChAT activity in the mature CNS. They also reveal the different efficacies of three diverse AS oligo chemistries when infused intracerebrally. Among the three types, gapmer oligos worked best. PMID- 26864467 TI - In response to Natural history and management of fanconi anemia patients with head and neck cancer: A 10-year follow-up. PMID- 26864468 TI - Using established forums to improve difficult doctor-patient relationships. PMID- 26864469 TI - Can venous ProBNP levels predict placenta accreta? AB - AIM: Placenta previa (PP) is a potential life-threatening pregnancy complication. Pro-brain natriuretic peptide (ProBNP), creatine kinase (CK), cardiac form of CK (CK-MB) and Troponin I are circulatory biomarkers related to cardiac functions. We aimed to determine whether these biomarkers are related to PP and placenta accreta. METHODS: In this case-control study, fifty-four pregnant women who attended our tertiary care center for perinatology with the diagnosis of PP totalis, and of them, 14 patients with placenta accreta were recruited as the study groups. Forty-six uncomplicated control patients who were matched for age, BMI were also included. Maternal venous ProBNP, CK, CK-MB and Troponin I levels were compared between the three groups. RESULTS: Obstetric history characteristics were comparable among groups, generally. CK and CK-MB levels were similar among three groups. Troponin I levels in the previa and accreta groups were significantly higher than the controls. ProBNP levels in the accreta group were significantly higher than other two groups. The multivariate regression model revealed that ProBNP could predict placental adhesion anomalies. CONCLUSIONS: Troponin I and ProBNP levels in PP cases were higher than controls and ProBNP could predict placenta accreta. PMID- 26864470 TI - A simple, step-by-step dissection protocol for the rapid isolation of mouse dorsal root ganglia. AB - BACKGROUND: The cell bodies of sensory neurons, which transmit information from the external environment to the spinal cord, can be found at all levels of the spinal column in paired structures called dorsal root ganglia (DRG). Rodent DRG neurons have long been studied in the laboratory to improve understanding of sensory nerve development and function, and have been instrumental in determining mechanisms underlying pain and neurodegeneration in disorders of the peripheral nervous system. Here, we describe a simple, step-by-step protocol for the swift isolation of mouse DRG, which can be enzymatically dissociated to produce fully differentiated primary neuronal cultures, or processed for downstream analyses, such as immunohistochemistry or RNA profiling. FINDINGS: After dissecting out the spinal column, from the base of the skull to the level of the femurs, it can be cut down the mid-line and the spinal cord and meninges removed, before extracting the DRG and detaching unwanted axons. This protocol allows the easy and rapid isolation of DRG with minimal practice and dissection experience. The process is both faster and less technically challenging than extracting the ganglia from the in situ column after performing a dorsal laminectomy. CONCLUSIONS: This approach reduces the time required to collect DRG, thereby improving efficiency, permitting less opportunity for tissue deterioration, and, ultimately, increasing the chances of generating healthy primary DRG cultures or high quality, reproducible experiments using DRG tissue. PMID- 26864471 TI - Pesticide residue determination in vegetables from western China applying gas chromatography with mass spectrometry. AB - In this study,an effort has been made to evaluate the pesticide residues in vegetables from western China. Fifty-one pesticides, including organophosphorus, organochlorine, carbamate and pyrethroid, were detected in 369 commonly used vegetables by GC-MS. Concentrations of organophosphorus pesticides were detected ranging from 0.0008 to 18.8200 mg/kg, among which organophosphorus pesticide concentrations exceeded their maximum residue levels (MRLs) in five samples. Carbamate and organochlorine pesticides were determined to have concentrations in the range of 0.0012-0.7928 mg/kg. The residual concentrations of carbamate pesticides in six samples and organochlorine pesticides in four samples exceeded their MRLs. The residual concentrations of five pyrethroid pesticides were within the range of 0.0016-6.0827 mg/kg and the pyrethroid residues in two samples exceeded their MRLs. The results revealed that pesticide residues in 70.73% of the vegetables samples were not detected, while in the rest of vegetables there were one or more pesticide residues and some even exceeded their MRLs, which would threaten the health of consumers. Our work provides significant information for the food safety regulations to control the excessive use of some pesticides on those kinds of vegetables from western China. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864472 TI - The utility of dual-energy X-ray absorptiometry, calcaneal quantitative ultrasound, and fracture risk indices (FRAX(r) and Osteoporosis Risk Assessment Instrument) for the identification of women with distal forearm or hip fractures: A pilot study. AB - PURPOSE: Dual-energy X-ray absorptiometry (DXA) is considered the "gold standard" in predicting osteoporotic fractures. Calcaneal quantitative ultrasound (QUS) variables are also known to predict fractures. Fracture risk assessment tools may also guide us for the detection of individuals at high risk for fractures. The aim of this case-control study was to evaluate the utility of DXA bone mineral density (BMD), calcaneal QUS parameters, FRAX(r) (Fracture Risk Assessment Tool), and Osteoporosis Risk Assessment Instrument (ORAI) for the discrimination of women with distal forearm or hip fractures. MATERIALS AND METHODS: This case control study included 20 women with a distal forearm fracture and 18 women with a hip fracture as cases and 76 age-matched women served as controls. BMD at the spine, proximal femur, and radius was measured using DXA and acoustic parameters of bone were obtained using a calcaneal QUS device. FRAX(r) 10-year probability of fracture and ORAI scores were also calculated in all participants. Receiver operating characteristic (ROC) analysis was used to assess fracture discriminatory power of all the tools. RESULTS: While all DXA BMD, and QUS variables and FRAX(r) fracture probabilities demonstrated significant areas under the ROC curves for the discrimination of hip-fractured women and those without, only 33% radius BMD, broadband ultrasound attenuation (BUA), and FRAX(r) major osteoporotic fracture probability calculated without BMD showed significant discriminatory power for distal forearm fractures. CONCLUSIONS: It can be concluded that QUS variables, particularly BUA, and FRAX(r) major osteoporotic fracture probability without BMD are good candidates for the identification of both hip and distal forearm fractures. PMID- 26864473 TI - Will the UK's new alcohol guidelines change hearts, minds--and livers? PMID- 26864432 TI - The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species. AB - The genus Trichoderma contains fungi with high relevance for humans, with applications in enzyme production for plant cell wall degradation and use in biocontrol. Here, we provide a broad, comprehensive overview of the genomic content of these species for "hot topic" research aspects, including CAZymes, transport, transcription factors, and development, along with a detailed analysis and annotation of less-studied topics, such as signal transduction, genome integrity, chromatin, photobiology, or lipid, sulfur, and nitrogen metabolism in T. reesei, T. atroviride, and T. virens, and we open up new perspectives to those topics discussed previously. In total, we covered more than 2,000 of the predicted 9,000 to 11,000 genes of each Trichoderma species discussed, which is >20% of the respective gene content. Additionally, we considered available transcriptome data for the annotated genes. Highlights of our analyses include overall carbohydrate cleavage preferences due to the different genomic contents and regulation of the respective genes. We found light regulation of many sulfur metabolic genes. Additionally, a new Golgi 1,2-mannosidase likely involved in N linked glycosylation was detected, as were indications for the ability of Trichoderma spp. to generate hybrid galactose-containing N-linked glycans. The genomic inventory of effector proteins revealed numerous compounds unique to Trichoderma, and these warrant further investigation. We found interesting expansions in the Trichoderma genus in several signaling pathways, such as G protein-coupled receptors, RAS GTPases, and casein kinases. A particularly interesting feature absolutely unique to T. atroviride is the duplication of the alternative sulfur amino acid synthesis pathway. PMID- 26864474 TI - Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand. AB - Associative learning is essential for establishing appropriate responses to cause effect relationships and effective behavioral adjustments to environmental changes. However, learned associations also promote maladaptive behavior such as uncontrollable drug seeking in addicts exposed to drug-associated stimuli. Here, we sought to identify behavioral characteristics that distinguish reward seeking produced by environmental stimuli conditioned to highly potent but non-addictive conventional reinforcers from reward seeking induced by stimuli conditioned to addictive drugs. Rats were trained to associate discriminative (i.e. contextual) stimuli (S+ ) with availability of cocaine, ethanol, palatable sweet solutions or water during dehydration. Following extinction, response-reinstating effects of re-exposure to these stimuli were established in terms of magnitude and perseveration. Initially, the S+ produced strong reinstatement irrespective of association with conventional or drug reward. However, with repeated testing, S+ induced reward seeking decreased to extinction levels when motivated by the sweet solutions but perseverated when motivated by cocaine or ethanol. In rats placed on water restriction to induce a motivational constraint, the S+ supported perseverating reinstatement identical to that produced by an S+ conditioned to cocaine. The findings suggest that behavior guided by associations between environmental stimuli and drugs of abuse is characterized by perseverating, apparently highly extinction-resistant reward seeking, whereas behavior controlled by stimuli associated with conventional reward extinguishes rapidly in the absence of primary reinforcement. Reward seeking elicited by stimuli associated with natural reward can, however, become perseverative during physiological deprivation states. Possibly, perseverating drug seeking engages mechanisms overlapping with those that have evolved to promote alleviation of physiological deprivation to secure survival. PMID- 26864475 TI - Evaluating the efficacy of restoration plantings through DNA barcoding of frugivorous bird diets. AB - Frugivores are critical components of restoration programs because they are seed dispersers. Thus, knowledge about bird-plant trophic relationships is essential in the evaluation of the efficacy of restoration processes. Traditionally, the diet of frugivores is characterized by microscopically identifying plant residues in droppings, which is time-consuming, requires botanical knowledge, and cannot be used for fragments lacking detectable morphological characteristics (e.g., fragmented seeds and skins). We examined whether DNA barcoding can be used as a universal tool to rapidly characterize the diet of a frugivorous bird, Eurasian blackcap (Sylvia atricapilla). We used the DNA barcoding results to assess restoration efforts and monitor the diversity of potentially dispersed plants in a protected area in northern Italy. We collected 642 Eurasian Blackcap droppings at the restored site during the autumn migration over 3 years. Intact seeds and fragmented plant material were analyzed at 2 plastidial barcode loci (rbcL and trnH-psbA), and the resulting plant identifications were validated by comparison with a reference molecular data set of local flora. At least 17 plant species, including 7 of the 11 newly transplanted taxa, were found. Our results demonstrate the potential for DNA barcoding to be used to monitor the effectiveness of restoration plantings and to obtain information about fruit consumption and dispersal of invasive or unexpected plant species. Such an approach provides valuable information that could be used to study local plant biodiversity and to survey its evolution over time. PMID- 26864477 TI - C15271. The Chemical Diversity of Lantana camara: Analyses of Essential Oil Samples from Cuba, Nepal, and Yemen. AB - The aerial parts of Lantana camara L. were collected from three different geographical locations: Artemisa (Cuba), Biratnagar (Nepal), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography - mass spectrometry. A cluster analysis of 39 L. camara essential oil compositions revealed eight major chemotypes: beta-caryophyllene, germacrene D, ar-curcumene/zingiberene, gamma-curcumen-15-al/epi-beta-bisabolol, (E) nerolidol, davanone, eugenol/alloaromadendrene, and carvone. The sample from Cuba falls into the group dominated by (E)-nerolidol, the sample from Nepal is a davanone chemotype, and the sample from Yemen belongs to the beta-caryophyllene chemotype. The chemical composition of L. camara oil plays a role in the biological activity; the beta-caryophyllene and (E)-nerolidol chemotypes showed antimicrobial and cytotoxic activities. This article is protected by copyright. All rights reserved. PMID- 26864476 TI - Electrical synapses and the development of inhibitory circuits in the thalamus. AB - KEY POINTS: The thalamus is a structure critical for information processing and transfer to the cortex. Thalamic reticular neurons are inhibitory cells interconnected by electrical synapses, most of which require the gap junction protein connexin36 (Cx36). We investigated whether electrical synapses play a role in the maturation of thalamic networks by studying neurons in mice with and without Cx36. When Cx36 was deleted, inhibitory synapses were more numerous, although both divergent inhibitory connectivity and dendritic complexity were reduced. Surprisingly, we observed non-Cx36-dependent electrical synapses with unusual biophysical properties interconnecting some reticular neurons in mice lacking Cx36. The results of the present study suggest an important role for Cx36 dependent electrical synapses in the development of thalamic circuits. ABSTRACT: Neurons within the mature thalamic reticular nucleus (TRN) powerfully inhibit ventrobasal (VB) thalamic relay neurons via GABAergic synapses. TRN neurons are also coupled to one another by electrical synapses that depend strongly on the gap junction protein connexin36 (Cx36). Electrical synapses in the TRN precede the postnatal development of TRN-to-VB inhibition. We investigated how the deletion of Cx36 affects the maturation of TRN and VB neurons, electrical coupling and GABAergic synapses by studying wild-type (WT) and Cx36 knockout (KO) mice. The incidence and strength of electrical coupling in TRN was sharply reduced, but not abolished, in KO mice. Surprisingly, electrical synapses between Cx36-KO neurons had faster voltage-dependent decay kinetics and conductance asymmetry (rectification) than did electrical synapses between WT neurons. The properties of TRN-mediated inhibition in VB also depended on the Cx36 genotype. Deletion of Cx36 increased the frequency and shifted the amplitude distributions of miniature IPSCs, whereas the paired-pulse ratio of evoked IPSCs was unaffected, suggesting that the absence of Cx36 led to an increase in GABAergic synaptic contacts. VB neurons from Cx36-KO mice also tended to have simpler dendritic trees and fewer divergent inputs from the TRN compared to WT cells. The findings obtained in the present study suggest that proper development of thalamic inhibitory circuitry, neuronal morphology, TRN cell function and electrical coupling requires Cx36. In the absence of Cx36, some TRN neurons express asymmetric electrical coupling mediated by other unidentified connexin subtypes. PMID- 26864478 TI - Biosensitive element in the form of immobilized luminescent photobacteria for detecting ecotoxicants in aqueous flow-through systems. AB - We demonstrated the possibility of long-term and efficient application of a biosensitive element (BE) in the form of Photobacterium phosphoreum photobacteria immobilized in poly(vinyl alcohol) (PVA) cryogel for detecting various ecotoxicants (Zn(2) (+) , Cu(2) (+) , Hg(2) (+) , Pb(2) (+) , 2,4 dichlorophenoxyacetic acid, 2,6-dimethylphenol, pentachlorophenol, coumaphos, malathion, chlorpyrifos and methyl parathion) in flow-through media. The range of detectable concentrations of ecotoxicants was determined at 1 * 10(-8) to 1 * 10( 4) M for heavy metal ions and at 1 * 10(-8) to 1 * 10(-5) M for phenol derivatives and organophosphorus pesticides. Immobilized cells of photobacteria quantitatively reacted with these ecotoxicants; cell sensitivity exhibited no flow rate dependence in the range from 45 to 180 mL/h. At a constant concentration of ecotoxicant in the flow, the bioluminescence quenching profile of immobilized cells demonstrated an integral response. The BE could remain in a flow-through medium for at least 10 days while retaining 95% of luminescent activity in the absence of ecotoxicants. The BE tested in this work was demonstrated to have a long shelf life (> 60 weeks) at -80 degrees C without changes in the baseline level of bioluminescence. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864479 TI - Automated Functional Imaging by 2D Speckle Tracking Echocardiography Reveals High Incidence of Abnormal Longitudinal Strain in a Cohort of Pediatric Oncology Patients. AB - BACKGROUND: Automated functional imaging (AFI) was introduced to two-dimensional speckle-tracking echocardiography to facilitate strain assessment in the clinical settings. In patients treated with cardiotoxic anthracyclines, AFI may be helpful in the detection of early myocardial injury when left ventricular ejection fraction (LVEF) remains normal. METHODS: We retrospectively assessed feasibility of AFI in 143 echocardiograms on 102 subjects aged 0.4-22 years (mean 12.3) obtained over a 12-month period. We computed a Z-score for apical four-chamber longitudinal strain using published normal data to assess for abnormal strain in patients with and without previous exposure to anthracyclines. RESULTS: AFI was feasible in 95.1% of echocardiograms, with low inter- and intraobserver variability. There was a statistically significant association between abnormal longitudinal strain Z-score (SZ < -2.0) and depressed LVEF (<55%, P < 0.001). However, 46% of echocardiograms with normal LVEF had abnormal SZ; half of which had no prior anthracycline exposure. The correlation between SZ and LVEF was strongest in subjects exposed to anthracyclines (r(2) = 0.12, P < 0.01). Increasing age was associated with decreasing SZ. Total cumulative dose, after adjusting for age, was inversely associated with SZ (r(2) = 0.42, P < 0.001). Time from last dose of anthracycline had no significant association with SZ. CONCLUSIONS: AFI is highly feasible in the clinical settings. The observed high prevalence of abnormal longitudinal strain in our cohort emphasizes the importance of obtaining baseline measurements prior to anthracycline treatment. The effects of anthracycline on longitudinal strain may be dose and age dependent, with younger children less likely to show abnormalities. PMID- 26864480 TI - Effect of Renal Reconstruction on Renal Function After Partial Nephrectomy. AB - BACKGROUND AND PURPOSE: Functional losses near 20% are seen in the operated kidney during partial nephrectomy. Resected healthy margins are small and ischemia time limited in the modern era. We hypothesize that reconstruction following tumor resection is modifiable and a significant cause of renal function injury. MATERIALS AND METHODS: A literature review of Medline and Scopus was performed for all available dates focusing on partial nephrectomy, renal function, and renal reconstruction. An additional review was performed evaluating recent advances in biomarkers of acute kidney injury. RESULTS: Serum creatinine is of limited value in measuring renal preservation during partial nephrectomy. Stimulated glomerular filtration rate can estimate renal reserve, but is more difficult to measure. CT-based three-dimensional measurements provide the ability to isolate ipsilateral functional loss. Newer urinary biomarkers of acute kidney injury such as kidney injury molecule-1 and cell cycle markers are emerging and might help to quantify renal function loss in real time. Most prior research has focused on ischemia and enucleation. However, despite minimizing both, significant renal function losses are still seen. Four retrospective controlled studies were found comparing cortical renorrhaphy to omission of cortical renorrhaphy. Three of the four found a statistical benefit to nonrenorrhaphy with the range of volume or functional loss in those three being 3.8% to 11.5% vs 15.6% to 20.4%. Urine leaks and bleeding complications were similar to reported rates for both groups. CONCLUSION: Studies evaluating renal function preservation after partial nephrectomy should control for reconstructive injury in addition to ischemia time and resected healthy margin. Cortical renorrhaphy is associated with renal volume and functional loss on retrospective studies, which might be especially relevant in the setting of chronic kidney disease or solitary kidney. Newer biomarkers of renal injury should be used when studying predictors of renal injury. PMID- 26864481 TI - Biomedical Applications of DNA-Conjugated Gold Nanoparticles. AB - Gold nanoparticles (AuNPs) are useful for diagnostic and biomedical applications, mainly because of their ease in preparation and conjugation, biocompatibility, and size-dependent optical properties. However, bare AuNPs do not possess specificity for targets. AuNPs conjugated with DNA aptamers offer specificity for various analytes, such as proteins and small molecules/ions. Although DNA aptamers themselves have therapeutic and target-recognizing properties, they are susceptible to degradation in vivo. When DNA aptamers are conjugated to AuNPs, their stability and cell uptake efficiency both increase, making aptamer-AuNPs suitable for biomedical applications. Additionally, drugs can be efficiently conjugated with DNA aptamer-AuNPs to further enhance their therapeutic efficiency. This review focuses on the applications of DNA aptamer-based AuNPs in several biomedical areas, including anticoagulation, anticancer, antibacterial, and antiviral applications. PMID- 26864482 TI - Cytogenetic confirmation of a positive NIPT result: evidence-based choice between chorionic villus sampling and amniocentesis depending on chromosome aberration. AB - It has been shown that in non-invasive prenatal testing (NIPT) there is a small chance of a false-positive or false-negative result. This is partly due to the fact that the fetal cell-free DNA present in maternal plasma is derived from the cytotrophoblast of chorionic villi (CV), which is not always representative for the fetal karyotype due to chromosomal mosaicism. Therefore, a positive NIPT result should always be confirmed with invasive testing, preferably amniocentesis, in order to investigate the fetal karyotype. However, since this invasive test can only be safely performed after 15.5 weeks of gestation while NIPT can be done from the 10(th) week of gestation, this potentially means an unacceptable long waiting time for the prospective parents to receive a definitive result. Based on our experience with cytogenetic investigations in CV and the literature, we determined whether CV sampling may be appropriate for confirmation of an abnormal NIPT result. PMID- 26864483 TI - T-cell internal antigen 1 counteracts somatic RNA degradation during early Xenopus embryogenesis. AB - In Xenopus laevis, maternal transcripts that localize to the vegetal cortex of the oocyte are specifically inherited by prospective germ cells during cleavage stages. While a large fraction of maternal transcripts is degraded during the maternal to zygotic transition (MZT), transcripts associated with the germ-line are stable. A sequence in the dead end 1 3'UTR mediates vegetal localization in the oocyte as well as miR mediated clearance in somatic cells and germ cell specific stabilization during the MZT in embryos. We could identify Tia1 to co precipitate with known components of vegetal localization RNPs in X. laevis oocytes. Tia1 interacts and co-localizes with various localization elements from vegetally localizing RNAs. In X. laevis embryos, ectopic expression of Tia1 counteracts somatic degradation of dnd1 localization element reporter RNAs and it can synergize with Dnd1 protein in reporter RNA stabilization. Ectopic Tia1 also protects several endogenous localizing and germ cell specific mRNAs from somatic degradation. Thus, proteins that protect germ-line transcripts from miR mediated decay during the MZT in embryos might bind these RNAs already in the oocyte. PMID- 26864484 TI - Ras-Related Nuclear Protein is required for late developmental stages of retinal cells in zebrafish eyes. AB - Ras-related nuclear protein (Ran) is involved in cell division by regulating nucleocytoplasmic transport and modulating the assembly of tubulin. However, its function in embryonic development is unclear. We used zebrafish to study the roles of Ran in eye development. The ran transcripts were restrictedly expressed in head and eyes after the pharyngula stage. The microphthalmos, in which no ordered layers with differentiated retinal cells were detected, was observed in the ran-deficient embryos. They exhibited faster decline cyclinD1-expressed cells, suggesting that cell cycle regulation in retinae was defective. The apoptotic signals in the retinae of ran-deficient embryos remained low at early (24 hpf) stage. Early eye field specification markers, rx1 and pax6, were only slightly affected, and markers for establishing axon migration, fgf8 and pax2, were normally expressed, suggesting Ran is not required in the early stages of eye development. However, the early optic nerve differentiation marker p57kip2 was not expressed at middle (48 hpf) and late (72 hpf) stages. We also observed a decrease in the retinal neuron proteins HuC and Neurolin. The proneural gene ath5, which first determines the cell fate of the developing ganglion cell layer, was undetectable. Furthermore, we found that Ran was associated with ADP ribosylation factor-like protein 6-interacting protein 1 (Arl6ip1), which plays a role in retinal development, suggesting that Ran associates with Arl6ip1 to regulate retinal development. Therefore, while the effects of Ran are minimal during early specification of the eye field, Ran is required for proliferation and differentiation of retinal cells at later developmental stages. PMID- 26864485 TI - Chicken primordial germ cell motility in response to stem cell factor sensing. AB - Avian primordial germ cells (PGCs) are destined to migrate a long distance from their extra embryonic region via the vascular system to the gonadal ridges where they form the germ cells. Although PGC migration is crucial for a genetic continuation to the next generation, the factors and mechanisms that control their migration remain largely unknown. In the present study the chemotactic effect of stem cell factor (SCF) was examined on chicken blood circulating PGCs (cPGC), employing 3D chemotaxis slides and time-lapsed imaging analyses as an in vitro study model. Upon in vitro exposure to an SCF gradient, 77.1% (54 out of 70) of cPGCs showed a clear response, of which 48.1% (26 out of 54) polarized with the consecutive formation of a persistent membrane protrusion and significant directional migration towards the gradient and the others showed transient membrane protrusions. In contrast, the controls and apparently SCF unresponsive cPGCs and c-kit-negative red blood cells (RBCs) showed only cytoplasmic cycling with random formations of membrane blebbing and no directional migration. Significant (p < 0.05) differences between the SCF-treated and control cPGCs and RBCs were found in the migration parameters of eccentricity, accumulated and Euclidean distances, and migration velocity. The SCF-treated PGCs also revealed a chemotactic response, as judged by their significant displacement of center of mass and Rayleigh test. Complete inhibition of all the SCF-induced responses in PGCs was found following pretreatment of the cPGCs with 10 uM of the c-kit inhibitor, STI57l, prior to SCF exposure. In addition, cPGCs were found to be positive for c-kit expression using a polyclonal goat anti-mouse c-kit primary antibody, suggesting that the cPGCs were capable of SCF sensing and the potential involvement of SCF/c-kit in the chemotactic migration. Therefore, SCF is suggested to function as a chemoattractant in the migration of chicken cPGC. PMID- 26864486 TI - Angiogenesis and hyperbaric oxygen in the chick embryo chorioallantoic membrane. AB - Hyperbaric Oxygen Therapy (HBOT) is increasingly applied in different areas of medical practice. The oxy-hyperbarism effects are not well understood in cancer malignancy. One unique feature of cancer is the presence of hypoxic regions that are insensitive to conventional therapies. It is possible to alter the hypoxic state and produce reactive oxygen species for better treatment outcome by HBOT. In the present study, we determined the effects of HBOT on angiogenesis, a signature of cancer progression, by using the chick chorioallantoic membrane (CAM) in vivo assay. CAMs were exposed to 2.0 ATA (atmospheres absolute) for 30 min of hyperbaric oxygen on the 6(th) and 7(th) days of incubation (ED6, ED7). On the 10-11(th) day of incubation, CAMs were excised from eggs, fixed and analysed using APERIO ImageScope software. HBOT outcomes were evaluated quantifying the volumetric area occupied by blood vessels and calculating the number of blood vessel ramifications. Results indicated that CAMs treated at ED6 and ED7 had a significantly higher CAM vascularization and an increased number of blood vessel ramifications (+82% higher for ED6) compared to untreated CAMs (ED6=63.3±2.5 and ED7=57.7±5.5 vs. CTRL=34.7±2.5). Thus, HBOT induces an angiogenic response in treated CAMs through a classic sprouting mechanism. PMID- 26864487 TI - Visualization of primordial germ cells in the fertilized pelagic eggs of the barfin flounder Verasper moseri. AB - Primordial germ cells (PGCs) appear during early embryogenesis and differentiate into gametes through oogenesis or spermatogenesis. Teleost PGCs can be visualized by injecting RNA transcribed from the fusion product of a fluorescent protein gene attached to the 3' untranslated region (3'UTR) of zebrafish nanos3 (zf nos3). Although this method has been widely applied to teleost PGCs, the visualization of PGCs in pelagic species that have eggs with a hard chorion is more problematic due to the technical difficulty of microinjection into their eggs. In this study, we developed a reliable method for microinjection of fertilized eggs in a pelagic species, the barfin flounder. Using a microneedle with a constriction "brake", we were able to introduce gfp-nos3 3'UTR mRNA into embryos and to determine the origin and migration route of PGCs. We also isolated the barfin flounder nos3 (bf-nos3) gene to compare its 3'UTR sequence with that of zebrafish. The 3'UTR of the bf-nos3 sequence was longer than that of zf-nos3. However, PGCs were also visualized after injection of gfp-bf-nos3 3'UTR mRNA both in zebrafish and barfin flounder. These results suggest that the function of nos3 is conserved between these species regardless of the sequence differences. The method developed here for labeling PGCs with gfp-nos3 mRNA will provide a means to study PGC development in the embryos of a wide range of marine fish species. PMID- 26864489 TI - iTRAQ-based proteomic analysis of adaptive response in the regenerating limb of the Cynops orientalis newt. AB - The newt has the powerful capacity to regenerate lost limbs following amputation, and represents an excellent model organism to study regenerative processes. However, the molecular basis of the adaptive response in the regenerating limb of the Chinese fire-bellied newt Cynops orientalis immediately after amputation remains unclear. To better understand the adaptive response immediately after limb amputation at the protein level, we used isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS methods to analyze changes in the proteome of the regenerating newt limb that occurred 2 h and 8 h after amputation. We identified 152 proteins with more than 1.5-fold change in expression compared to control. GO annotation analysis classified these proteins into several categories such as signaling, Ca(2+) binding and translocation, transcription and translation, immune response, cell death, cytoskeleton, metabolism, etc. Further ingenuity pathway analysis (IPA) showed that several signaling pathways were significantly changed at 2 h and 8 h after amputation, including EIF2 signaling, acute phase response signaling, tight junction signaling and calcium signaling, suggesting these pathways may be closely related to the adaptive response immediately after limb amputation. This work provides novel insights into understanding the molecular processes related to newt limb regeneration immediately after amputation, and a basis for further study of regenerative medicine. PMID- 26864488 TI - Expression of Sox genes in tooth development. AB - Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development. PMID- 26864490 TI - External ear microRNA expression profiles during mouse development. AB - MicroRNAs (miRNAs) comprise a class of approximately 22 nucleotide regulatory non coding RNAs that play several roles in diverse biological processes. Recent reports suggest that embryonic development in mammals is accompanied by dynamic changes in miRNA expression; however, there is no information regarding the role of miRNAs in the development of the external ear. The aim of this study was to determine the stage-specific expression of miRNAs during mouse external ear development in order to identify potentially implicated miRNAs along with their possible targets. miRNA expression profiles from fetal mice pinnae and back skin tissues at 13.5 dpc and 14.5 dpc were obtained using an Affymetrix GeneChip miRNA 3.0 array. Biological triplicates for both tissues, each collected from a litter averaging 16 fetuses, were analyzed. The results were analyzed with Affymetrix's Transcriptome Analysis Console software to identify differentially expressed miRNAs. We observed differential expression of 40 miRNAs including some predicted to target genes implicated in external ear development, such as mmu-miR-10a, an miRNA known to modulate Hoxa1 mRNA levels, and mmu-miR-200c and mmu-miR-205. To our knowledge, this is the first miRNA expression profiling study of external ear development in mammals. These data could set the basis to understand the implications of miRNAs in normal external ear development. PMID- 26864491 TI - CILP1 is dynamically expressed in the developing musculoskeletal system of the trout. AB - An in situ screen for genes expressed in the skeletal muscle of eyed-stage trout embryos led to the identification of a transcript encoding a polypeptide related to CILP1, a secreted glycoprotein present in the extracellular matrix. In situ hybridisation in developing trout embryos revealed that CILP1 expression was initially detected in fast muscle progenitors of the early somite. Later, CILP1 expression was down-regulated medio-laterally in differentiating fast muscle cells, to become finally restricted to the undifferentiated muscle progenitors forming the dermomyotome-like epithelium at the surface of the embryonic myotome. At the completion of somitogenesis, CILP1 expression was concentrated in the myoseptal/tendon cells that develop between adjacent myotomes but was excluded from the skeletogenic cells of the vertebral axis to which the most medial myoseptal/tendon cells attach. Overall, our work shows that muscle cells and myoseptal/tendon cells contribute dynamically and cooperatively to the production of CILP1 during ontogeny of the trout musculoskeletal system. PMID- 26864492 TI - Developmental expression of the N-myc downstream regulated gene (Ndrg) family during Xenopus tropicalis embryogenesis. AB - The N-myc downstream regulated gene (Ndrg) family consists of four main members Ndrg1, 2, 3, and 4. The Ndrg genes are involved in many vital biological events including development. However, comprehensive expression patterns of this gene family during vertebrate embryogenesis remain largely unknown. Here, we analyzed the Ndrg family from the evolutionary perspective and examined the expression patterns of the Ndrg genes during Xenopus tropicalis embryogenesis. Different Ndrg family members of vertebrates are separated into different homology clusters which can be further classified into two groups and each Ndrg family member is well conserved during evolution. The temporal and spatial expression patterns of Ndrg1, 2, 3 and 4 are different during early Xenopus tropicalis development. Ndrg1, 2 and 4 are maternally expressed genes while Ndrg3 is a zygotically expressed gene. The Ndrg genes are differentially expressed in the developing central nervous system, the developing sensory organs, and the developing excretory organs. Moreover, they also show other specific expression domains. Our results indicate that the Ndrg genes exhibit specific expression patterns and may play different roles during vertebrate embryogenesis. PMID- 26864493 TI - The last bastion of collegiality: the peer-review process in the era of open access. PMID- 26864494 TI - Canities subita: sudden blanching of the hair in history and literature. PMID- 26864495 TI - Efficient one-pot synthesis of 1-arylcycloprop-2-ene-1-carboxamides. AB - An expeditious and cost-efficient method for synthesis of 1-arylcycloprop-2-ene-1 carboxamides was developed. This one-pot protocol involving coupling of amines with acyl chlorides, generated upon treatment of cyclopenylcarboxylic acids with oxalyl chloride, is applicable for the preparation of sensitive products with a reactive, unsubstituted strained double bond. PMID- 26864496 TI - Metal-Organic Frameworks Stabilize Solution-Inaccessible Cobalt Catalysts for Highly Efficient Broad-Scope Organic Transformations. AB - New and active earth-abundant metal catalysts are critically needed to replace precious metal-based catalysts for sustainable production of commodity and fine chemicals. We report here the design of highly robust, active, and reusable cobalt-bipyridine- and cobalt-phenanthroline-based metal-organic framework (MOF) catalysts for alkene hydrogenation and hydroboration, aldehyde/ketone hydroboration, and arene C-H borylation. In alkene hydrogenation, the MOF catalysts tolerated a variety of functional groups and displayed unprecedentedly high turnover numbers of ~2.5 * 10(6) and turnover frequencies of ~1.1 * 10(5) h( 1). Structural, computational, and spectroscopic studies show that site isolation of the highly reactive (bpy)Co(THF)2 species in the MOFs prevents intermolecular deactivation and stabilizes solution-inaccessible catalysts for broad-scope organic transformations. Computational, spectroscopic, and kinetic evidence further support a hitherto unknown (bpy(*-))Co(I)(THF)2 ground state that coordinates to alkene and dihydrogen and then undergoing sigma-complex-assisted metathesis to form (bpy)Co(alkyl)(H). Reductive elimination of alkane followed by alkene binding completes the catalytic cycle. MOFs thus provide a novel platform for discovering new base-metal molecular catalysts and exhibit enormous potential in sustainable chemical catalysis. PMID- 26864497 TI - Hyperspectral imaging of nanoparticles in biological samples: Simultaneous visualization and elemental identification. AB - While engineered nanomaterials (ENMs) are increasingly incorporated into industrial processes and consumer products, the potential biological effects and health outcomes of exposure remain unknown. Novel advanced direct visualization techniques that require less time, cost, and resource investment than electron microscopy (EM) are needed for identifying and locating ENMs in biological samples. Hyperspectral imaging (HSI) combines spectrophotometry and imaging, using advanced optics and algorithms to capture a spectrum from 400 to 1000 nm at each pixel in an enhanced dark-field microscopic (EDFM) image. HSI-EDFM can be used to confirm the identity of the materials of interest in a sample and generate an image "mapping" their presence and location in a sample. Hyperspectral mapping is particularly important for biological samples, where ENM morphology is visually indistinct from surrounding tissue structures. While use of HSI (without mapping) is increasing, no studies to date have compared results from hyperspectral mapping with conventional methods. Thus, the objective of this study was to utilize EDFM-HSI to locate, identify, and map metal oxide ENMs in ex vivo histological porcine skin tissues, a toxicological model of cutaneous exposure, and compare findings with those of Raman spectroscopy (RS), energy dispersive X-ray spectroscopy (EDS), and scanning electron microscopy (SEM). Results demonstrate that EDFM-HSI mapping is capable of locating and identifying ENMs in tissue, as confirmed by conventional methods. This study serves as initial confirmation of EDFM-HSI mapping as a novel and higher throughput technique for ENM identification in biological samples, and serves as the basis for further protocol development utilizing EDFM-HSI for semiquantitation of ENMs. PMID- 26864498 TI - Silver nanoparticle film induced photoluminescence enhancement of near-infrared emitting PbS and PbS/CdS core/shell quantum dots: observation of different enhancement mechanisms. AB - The photoluminescence (PL) enhancement of a Ag nanoparticle and near-infrared quantum dots (QD) plasmon/fluorophore system was investigated. Different enhancement mechanisms were obtained by tuning surface plasmon resonance of the Ag film and PL of the QDs. A maximum enhancement factor of 2.8 was achieved. PMID- 26864500 TI - Hierarchical TiO2/C nanocomposite monoliths with a robust scaffolding architecture, mesopore-macropore network and TiO2-C heterostructure for high performance lithium ion batteries. AB - Engineering hierarchical structures of electrode materials is a powerful strategy for optimizing the electrochemical performance of an anode material for lithium ion batteries (LIBs). Herein, we report the fabrication of hierarchical TiO2/C nanocomposite monoliths by mediated mineralization and carbonization using bacterial cellulose (BC) as a scaffolding template as well as a carbon source. TiO2/C has a robust scaffolding architecture, a mesopore-macropore network and TiO2-C heterostructure. TiO2/C-500, obtained by calcination at 500 degrees C in nitrogen, contains an anatase TiO2-C heterostructure with a specific surface area of 66.5 m(2) g(-1). When evaluated as an anode material at 0.5 C, TiO2/C-500 exhibits a high and reversible lithium storage capacity of 188 mA h g(-1), an excellent initial capacity of 283 mA h g(-1), a long cycle life with a 94% coulombic efficiency preserved after 200 cycles, and a very low charge transfer resistance. The superior electrochemical performance of TiO2/C-500 is attributed to the synergistic effect of high electrical conductivity, anatase TiO2-C heterostructure, mesopore-macropore network and robust scaffolding architecture. The current material strategy affords a general approach for the design of complex inorganic nanocomposites with structural stability, and tunable and interconnected hierarchical porosity that may lead to the next generation of electrochemical supercapacitors with high energy efficiency and superior power density. PMID- 26864499 TI - Evaluation of agarose gel electrophoresis for characterization of silver nanoparticles in industrial products. AB - Agarose gel electrophoresis (AGE) has been used extensively for characterization of pure nanomaterials or mixtures of pure nanomaterials. We have evaluated the use of AGE for characterization of Ag nanoparticles (NPs) in an industrial product (described as strong antiseptic). Influence of different stabilizing agents (PEG, SDS, and sodium dodecylbenzenesulfonate), buffers (TBE and Tris Glycine), and functionalizing agents (mercaptosuccinic acid (TMA) and proteins) has been investigated for the characterization of AgNPs in the industrial product using different sizes-AgNPs standards. The use of 1% SDS, 0.1% TMA, and Tris Glycine in gel, electrophoresis buffer and loading buffer led to the different sizes-AgNPs standards moved according to their size/charge ratio (obtaining a linear relationship between apparent mobility and mean diameter). After using SDS and TMA, the behavior of the AgNPs in the industrial product (containing a casein matrix) was completely different, being not possible their size characterization. However we demonstrated that AGE with LA-ICP-MS detection is an alternative method to confirm the protein corona formation between the industrial product and two proteins (BSA and transferrin) maintaining NPs-protein binding (what is not possible using SDS-PAGE). PMID- 26864501 TI - Self-induced synthesis of phase-junction TiO2 with a tailored rutile to anatase ratio below phase transition temperature. AB - The surface phase junction of nanocrystalline TiO2 plays an essential role in governing its photocatalytic activity. Thus, facile and simple methods for preparing phase-junction TiO2 photocatalysts are highly desired. In this work, we show that phase-junction TiO2 is directly synthesized from Ti foil by using a simple calcination method with hydrothermal solution as the precursor below the phase transition temperature. Moreover, the ratio of rutile to anatase in the TiO2 samples could be readily tuned by changing the ratio of weight of Ti foil to HCl, which is used as the hydrothermal precursor, as confirmed by the X-ray diffraction analysis. In the photocatalytic reaction by the TiO2 nanocomposite, a synergistic effect between the two phases within a certain range of the ratio is clearly observed. The results suggest that an appropriate ratio of anatase to rutile in the TiO2 nanocomposite can create more efficient solid-solid interfaces upon calcination, thereby facilitating interparticle charge transfer in the photocatalysis. PMID- 26864502 TI - Improved chemical and mechanical stability of peptoid nanosheets by photo crosslinking the hydrophobic core. AB - Peptoid nanosheets can be broadly functionalized for a variety of applications. However, they are susceptible to degradation when exposed to chemical or mechanical stress. To improve their strength, photolabile monomers were introduced in order to crosslink the nanosheet interior. Photo-crosslinking produced a more robust material that can survive sonication, lyophilization, and other biochemical manipulations. PMID- 26864503 TI - Amorphous Molybdenum Sulfide on Graphene-Carbon Nanotube Hybrids as Highly Active Hydrogen Evolution Reaction Catalysts. AB - In this study, we report on the deposition of amorphous molybdenum sulfide (MoSx, with x ~ 3) on a high specific surface area conductive support of Graphene-Carbon Nanotube hybrids (GCNT) as the Hydrogen Evolution Reaction (HER) catalysts. We found that the high surface area GCNT electrode could support the deposition of MoSx at much higher loadings compared with simple porous carbon paper or flat graphite paper. The morphological study showed that MoSx was successfully deposited on and was in good contact with the GCNT support. Other physical characterization techniques suggested the amorphous nature of the deposited MoSx. With a typical catalyst loading of 3 mg cm(-2), an overpotential of 141 mV was required to obtain a current density of 10 mA cm(-2). A Tafel slope of 41 mV decade(-1) was demonstrated. Both measures placed the MoSx-deposited GCNT electrode among the best performing molybdenum sulfide-based HER catalysts reported to date. The electrode showed a good stability with only a 25 mV increase in overpotential required for a current density of 10 mA cm(-2), after undergoing 500 potential sweeps with vigorous bubbling present. The current density obtained at -0.5 V vs SHE (Standard Hydrogen Electrode potential) decreased less than 10% after the stability test. The deposition of MoSx on high specific surface area conductive electrodes demonstrated to be an efficient method to maximize the catalytic performance toward HER. PMID- 26864504 TI - Physician-Assisted Death for Patients With Mental Disorders-Reasons for Concern. PMID- 26864505 TI - Endovascular treatment of large and wide aortic neck: case report and literature review. AB - Large (24-34 mm) and wide (>=35 mm) aortic necks are a contraindication to endovascular aneurysm repair (EVAR). A 63-year-old man, unfit for conventional surgery, presented a 79 mm abdominal aortic aneurysm with 36.5 mm aortic neck and a 62 mm right common iliac artery aneurysm. He was treated endovascularly with standard commercially available stent-graft using the so-called 'funnel technique'; by placing a thoracic stent-graft inside a bifurcated device to achieve proximal sealing. The completion angiography and the 6 months follow-up with computed tomography showed no stent-graft migration, limb occlusion or endoleak. The literature review reported 179 cases of large aortic neck managed with EVAR, all cases treated with standard devices. Conversely a wide aortic neck was reported in 9; in 2 cases were employed custom-made devices and in 7 standard stent-graft. The use of EVAR with commercially available stent-grafts is feasible and it represents an option especially in non-elective setting. PMID- 26864506 TI - The Stomatological Complications of Diamond-Blackfan Anemia: A Case Report. AB - Diamond-Blackfan Anemia (DBA) is a rare heterogeneous genetic disease characterized by severe anemia, reduction or absence of erythroid progenitors, and pro-apoptoptic hematopoiesis, which culminates in bone marrow failure. The disease generally manifests in infancy, as craniofacial, cardiac, genitourinary, and upper limb congenital anomalies. Therapy with corticoids is the treatment of choice, while blood transfusion is adopted during diagnosis and as a chronic approach if the patient does not respond to corticoids. This case report describes DBA in a patient that presented with lesions on the oral mucosa caused by secondary neutropenia. The stomatologist plays an important role in a transdisciplinary team and must remain attentive to the general health conditions of patients, since some oral lesions may be associated with systemic events. PMID- 26864507 TI - Transient Hypothyroidism after Radioiodine for Graves' Disease: Challenges in Interpreting Thyroid Function Tests. AB - Graves' disease is the most common cause of hyperthyroidism and is often managed with radioactive iodine (RAI) therapy. With current dosing schemes, the vast majority of patients develop permanent post-RAI hypothyroidism and are placed on life-long levothyroxine therapy. This hypothyroidism typically occurs within the first 3 to 6 months after RAI therapy is administered. Indeed, patients are typically told to expect life-long thyroid hormone replacement therapy to be required within this timeframe and many providers expect this post-RAI hypothyroidism to be complete and permanent. There is, however, a small subset of patients in whom a transient post-RAI hypothyroidism develops which, initially, presents exactly as the typical permanent hypothyroidism. In some cases the transient hypothyroidism leads to a period of euthyroidism of variable duration eventually progressing to permanent hypothyroidism. In others, persistent hyperthyroidism requires a second dose of RAI. Failure to appreciate and recognize the possibility of transient post-RAI hypothyroidism can delay optimal and appropriate treatment of the patient. We herein describe five cases of transient post-RAI hypothyroidism which highlight this unusual sequence of events. Increased awareness of this possible outcome after RAI for Graves' disease will help in the timely management of patients. PMID- 26864508 TI - Oral Manifestations of Inflammatory Bowel Diseases: Two Case Reports. AB - Inflammatory bowel diseases (IBD) are known as chronic inflammatory disorders of the digestive tract, represented mainly by Crohn's disease (CD) and ulcerative colitis (UC). Among the main oral manifestations of IBD are cobblestoning of the oral mucosa, labial swellings with vertical fissures, pyostomatitis vegetans, angular cheilitis, perioral erythema, and glossitis. In this sense, understanding these nosological entities by dentists would help reach early and differential diagnosis. Thus, two case reports are presented and discussed based on theoretical references obtained by a literature review. The first case report refers to an adult patient whose IBD diagnosis was established after stomatological assessment. The second case was a patient with CD diagnosed in childhood with characteristic oral lesions. PMID- 26864509 TI - Web Camera Use in the Neonatal Intensive Care Unit: Impact on Nursing Workflow. AB - BACKGROUND: Many neonatal intensive care units (NICU) are using web camera systems to allow virtual visitation of the infant by family members. Generally, families appreciate the web camera and utilize this service. However, no one has looked into the change on nursing workload after implementation of a web camera. OBJECTIVE: This study was designed to explore the perception of nurses and their workflow and identify determinants that may disrupt or facilitate the use of a commercially available camera service. Our primary goal was to see if the camera system interferes with the nursing care. STUDY DESIGN: This was a prospective, questionnaire-based study conducted between March and September 2014. Parents were offered the camera service and signed a consent form before use. Parents who refused the camera were the group designated as "off camera." There were two infant groups; one cared for using the cameras and the other not. The camera service was used continuously during the study period, except during procedures, baby care, and feedings. Demographic information on nursing staff and neonates was collected weekly. Questionnaires were placed at each bedside for nurses to complete on each shift for each infant once weekly. The questionnaires for infants off-camera did not have questions regarding the camera. However, the rest of the questions were similar regarding time spent interacting with family members, face to face, or on the phone. Data on time spent manipulating the camera per shift were also obtained. RESULTS: Surveys for 623 on-camera and 130 off-camera infants were completed by 42 nursing staff. Findings showed that caring for multiple infants while using the web camera increased nurses' workload and stress, which they perceived as having an adverse effect on the ability to provide quality care. Family decisions not to utilize the camera service were mainly cultural, and noted among Mennonite, Amish, and Hmong families. Some families residing close to the hospital also preferred visiting the baby personally rather than using the camera service. CONCLUSION: Parents and nurses perceived web cameras as beneficial in the NICU setting. However, nurses spent significant time manipulating cameras and addressing parental concerns over the phone, causing disruption in their workflow, which had the potential to decrease quality of care for infants. To compensate for these disruptions, we recommend increasing awareness of the potential issues with both cameras and families and providing multiple training sessions to nursing staff before systems are implemented. PMID- 26864510 TI - Discovery and enantiocontrol of axially chiral urazoles via organocatalytic tyrosine click reaction. AB - Axially chiral compounds play an important role in areas such as asymmetric catalysis. The tyrosine click-like reaction is an efficient approach for synthesis of urazoles with potential applications in pharmaceutical and asymmetric catalysis. Here we discover a class of urazole with axial chirality by restricted rotation around an N-Ar bond. By using bifunctional organocatalyst, we successfully develop an organocatalytic asymmetric tyrosine click-like reaction in high yields with excellent enantioselectivity under mild reaction conditions. The excellent remote enantiocontrol of the strategy originates from the efficient discrimination of the two reactive sites in the triazoledione and transferring the stereochemical information of the catalyst into the axial chirality of urazoles at the remote position far from the reactive site. PMID- 26864511 TI - Beyond organic chemistry: aromaticity in atomic clusters. AB - We describe joint experimental and theoretical studies carried out collaboratively in the authors' labs for understanding the structures and chemical bonding of novel atomic clusters, which exhibit aromaticity. The concept of aromaticity was first discovered to be useful in understanding the square planar unit of Al4 in a series of MAl4(-) bimetallic clusters that led to discoveries of aromaticity in many metal cluster systems, including transition metals and similar cluster motifs in solid compounds. The concept of aromaticity has been found to be particularly powerful in understanding the stability and bonding in planar boron clusters, many of which have been shown to be analogous to polycyclic aromatic hydrocarbons in their pi bonding. Stimulated by the multiple aromaticity in planar boron clusters, a design principle has been proposed for stable metal-cerntered aromatic molecular wheels of the general formula, M@Bn(k-). A series of such borometallic aromatic wheel complexes have been produced in supersonic cluster beams and characterized experimentally and theoretically, including Ta@B10(-) and Nb@B10(-), which exhibit the highest coordination number in two dimensions. PMID- 26864512 TI - Analyzing the Release of Copeptin from the Heart in Acute Myocardial Infarction Using a Transcoronary Gradient Model. AB - Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done. PMID- 26864515 TI - An Algorithmic Approach to the Diagnosis and Management of the Thrombotic Microangiopathies. PMID- 26864513 TI - Changes in Type 2 Diabetes Mellitus Patients in German Primary Care Prior to (2006) and After (2010, 2014) Launch of New Drugs. AB - AIMS: The aim was to analyze the changes in a German type 2 diabetes population prior to (2006) and after (2010, 2014) launch of new drugs. METHODS: Patients with T2DM in 2006, 2010, and 2014 were recruited for the study. Demographic data included age, gender, and health insurance type (private/statutory). Drug prescription, mean costs per patient, HbA1c levels, macrovascular complications, and time before first insulin prescription were analyzed. RESULTS: In all, 64 098, 77 219, and 85 004 T2DM patients were included for 2006, 2010, and 2014, respectively. The mean age (65.9-66.9 years), proportion of men (50.8%-53.8%), and proportion of patients with private health insurance (6.6%-7.2%) differed significantly for each of the 3 years. There was a 1.25-fold increase in the total costs per patient, linked with an increase in the costs associated with the use of new drugs and a decrease in those associated with the use of old drugs, respectively. HbA1c levels were slightly better regulated in 2014 than in 2006 and 2010. The share of macrovascular complications decreased significantly over time, dropping from 27.4% in 2006 to 24.6% in 2014. The mean duration before first insulin treatment increased from 1225 days in 2006 to 1406 days in 2014. CONCLUSIONS: The new drugs analyzed in this study had positive effects on HbA1c levels, macrovascular complications, and mean time before first insulin treatment. PMID- 26864516 TI - Deceased Donor Kidney Transplantation in the Eurotransplant Senior Program (ESP): A Single-Center Experience from 2008 to 2013. AB - BACKGROUND: The aim of this study was to evaluate the outcome after transplantation of deceased allografts in donor/recipient pairs aged >=65 years enrolled in the Eurotransplant Senior Program (ESP). MATERIAL AND METHODS: In this retrospective cohort study we evaluated data from 89 patients transplanted under the ESP protocol from 2008 to 2013. Outcome parameters included graft and patient survival, rate of biopsy-proven acute rejections (BPAR), peri- and post operative complications, tumor development, development of donor-specific antibodies (DSA), and the prognostic role of preimplantation biopsies. RESULTS: One-year patient and allograft survival rates were 92.1% and 84.3%, respectively. During follow-up, 23 (26%) patients died; the major cause of death was sepsis, followed by cardiovascular events and malignancies. BPAR episodes were frequent within the first year (~33%) and overall were less common in patients treated with tacrolimus. Post-transplant malignancies were seen in 15 (17%) patients. During follow-up, 16 (18%) patients developed DSA; patients with delayed graft function (DGF) were more likely to develop DSA (p=0.029). A higher preimplantation biopsy score was associated with DGF but did not predict later graft outcome. CONCLUSIONS: The results highlight increased risks in ESP transplant candidates and the importance of careful surveillance of this patient group. PMID- 26864517 TI - Assessment of the latest NGS enrichment capture methods in clinical context. AB - Enrichment capture methods for NGS are widely used, however, they evolve rapidly and it is necessary to periodically measure their strengths and weaknesses before transfer to diagnostic services. We assessed two recently released custom DNA solution-capture enrichment methods for NGS, namely Illumina NRCCE and Agilent SureSelect(QXT), against a reference method NimbleGen SeqCap EZ Choice on a similar gene panel, sharing 678 kb and 110 genes. Two Illumina MiSeq runs of 12 samples each have been performed, for each of the three methods, using the same 24 patients (affected with sensorineural disorders). Technical outcomes have been computed and compared, including depth and evenness of coverage, enrichment in targeted regions, performance in GC-rich regions and ability to generate consistent variant datasets. While we show that the three methods resulted in suitable datasets for standard DNA variant discovery, we describe significant differences between the results for the above parameters. NimbleGen offered the best depth of coverage and evenness, while NRCCE showed the highest on target levels but high duplicate rates. SureSelect(QXT) showed an overall quality close to that of NimbleGen. The new methods exhibit reduced preparation time but behave differently. These findings will guide laboratories in their choice of library enrichment approach. PMID- 26864518 TI - Bacteriophage cell lysis of Shiga toxin-producing Escherichia coli for top-down proteomic identification of Shiga toxins 1 & 2 using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. AB - RATIONAL: Analysis of bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) often relies upon sample preparation methods that result in cell lysis, e.g. bead-beating. However, Shiga toxin-producing Escherichia coli (STEC) can undergo bacteriophage-induced cell lysis triggered by antibiotic exposure that may allow greater selectivity of the proteins extracted. METHODS: We have developed a sample preparation method for selective extraction of bacteriophage-encoded proteins and specifically Shiga toxins 1 and 2 (Stx1 & 2) expressed from STEC strains induced by DNA-damaging antibiotics. STEC strains were cultured overnight on agar supplemented with ciprofloxacin, mitomycin-C or an iron chelator to induce the bacteriophage lytic cycle with concomitant expression and release of Stx1 and/or Stx2. Sample preparation relied exclusively on bacteriophage lysis for release Stx into the extraction solution. RESULTS: Three clinical STEC strains were analyzed by matrix assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF-TOF-MS/MS) and top-down proteomics analysis: E. coli O157:H7 strain EDL933, E. coli O91:H21 strain B2F1 and E. coli O26:H11 strain ECRC #05.2217. The B-subunit of Stx1a of EDL933 was detected and identified even though it was ~100 fold less abundant than the B-subunit of Stx2a that had been identified previously for this strain. Two bacteriophage-encoded proteins were also identified: L0117 and L0136. The B-subunits of Stx2d of strain B2F1 and Stx1a of strain ECRC #05.2217 were also detected and identified. CONCLUSIONS: Bacteriophage lysis appeared to enhance the detection sensitivity of Stx for these STEC strains compared to previous work using mechanical lysis. Detection/identification of other bacteriophage-encoded proteins (beyond Stx) tends to support the hypothesis of Stx release by bacteriophage cell lysis. PMID- 26864519 TI - Polyalanine - a practical polypeptide mass calibration standard for matrix assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry in positive and negative mode. AB - RATIONALE: Mass calibration in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is currently obtained using mixtures of individual peptides. This procedure has several drawbacks, including laborious preparation, limited shelf life and unequal calibration mass spacing. Polyalanine, a simple to prepare polydisperse molar mass standard, alleviates these problems. METHODS: Polyalanine is prepared by the typical protocols for biological sample analytics. RESULTS: Polyalanine is the first polymeric standard providing abundant signals in both, positive and negative polarity mode with the typical matrices DHB and HCCA. CONCLUSIONS: Facile MS as well as MS/MS calibration is thus enabled for the first time in both polarity modes by employing this polydisperse standard. PMID- 26864520 TI - Measurement of oxygen isotope ratios ((18)O/(16)O) of aqueous O2 in small samples by gas chromatography/isotope ratio mass spectrometry. AB - RATIONALE: Oxygen isotope fractionation of molecular O2 is an important process for the study of aerobic metabolism, photosynthesis, and formation of reactive oxygen species. The latter is of particular interest for investigating the mechanism of enzyme-catalyzed reactions, such as the oxygenation of organic pollutants, which is an important detoxification mechanism. METHODS: We developed a simple method to measure the delta(18) O values of dissolved O2 in small samples using automated split injection for gas chromatography coupled to isotope ratio mass spectrometry (GC/IRMS). After creating a N2 headspace, the dissolved O2 partitions from aqueous solution to the headspace, from which it can be injected into the gas chromatograph. RESULTS: In aqueous samples of 10 mL and in diluted air samples, we quantified the delta(18) O values at O2 concentrations of 16 MUM and 86 MUM, respectively. The chromatographic separation of O2 and N2 with a molecular sieve column made it possible to use N2 as the headspace gas for the extraction of dissolved O2 from water. We were therefore able to apply a rigorous delta(18) O blank correction for the quantification of (18) O/(16) O ratios in 20 nmol of injected O2 . CONCLUSIONS: The successful quantification of (18) O kinetic isotope effects associated with enzymatic and chemical reduction of dissolved O2 illustrates how the proposed method can be applied for studying enzymatic O2 activation mechanisms in a variety of (bio)chemical processes. PMID- 26864521 TI - An online method for the analysis of volatile organic compounds in electronic cigarette aerosol based on proton transfer reaction mass spectrometry. AB - RATIONALE: Due to the recent rapid increase in electronic cigarette (e-cigarette) use worldwide, there is a strong scientific but also practical interest in analyzing e-cigarette aerosols. Most studies to date have used standardized but time-consuming offline technologies. Here a proof-of-concept for a fast online quantification setup based on proton transfer reaction mass spectrometry (PTR-MS) is presented. METHODS: The combination of a novel sampling interface with a time of-flight PTR-MS instrument specially designed for three scenarios is introduced: (i) mainstream aerosol analysis (aerosol that the user inhales prior to exhalation), and analysis of exhaled breath following (ii) mouth-hold (no inhalation) and (iii) inhalation of e-cigarette aerosols. A double-stage dilution setup allows the various concentration ranges in these scenarios to be accessed. RESULTS: First, the instrument is calibrated for the three principal constituents of the e-cigarettes' liquids, namely propylene glycol, vegetable glycerol and nicotine. With the double-stage dilution the instrument's dynamic range was easily adapted to cover the concentration ranges obtained in the three scenarios: 20-1100 ppmv for the mainstream aerosol characterisation; 4-300 ppmv for the mouth-hold; and 2 ppbv to 20 ppmv for the inhalation experiment. CONCLUSIONS: It is demonstrated that the novel setup enables fast, high time resolution e cigarette studies with online quantification. This enables the analysis and understanding of any puff-by-puff variations in e-cigarette aerosols. Large-scale studies involving a high number of volunteers will benefit from considerably higher sample throughput and shorter data processing times. PMID- 26864522 TI - Removal of sodium dodecyl sulfate from protein and peptide samples with cross linked [Os(dmebpy)2 Cl](+/2+) -derivatized acrylamide and vinylimidazole copolymer. AB - RATIONALE: Sodium dodecyl sulfate (SDS) is widely used for the solubilization and denaturation of proteins, but it interferes with liquid chromatography/mass spectrometry (LC/MS), suppressing protein signals or forming adduct ions. A quick and effective clean-up technique of SDS is essential for MS analysis of proteins. Ion-exchange spin columns are commonly used for SDS removal in protein samples. METHODS: A bulk sample of insoluble, cross-linked [Os(dimethylbipyridine)2 Cl](+/2+) -derivatized poly(acrylamide)-poly(vinylimidazole) copolymer was synthesized and broken into small particles. The polymer was activated by washing with 1:1 ACN/water 50 mM triethylammonium phosphate 0.05% TFA, 0.1% TFA ACN and then 0.1% TFA water. Under acidic aqueous conditions, SDS adsorbs on the activated surfaces of the Os-complexed copolymer particles, but not the proteins and peptides in the same mixtures. Thus, the copolymer can be used to remove SDS from protein and peptide samples. The copolymer-adsorbed SDS is removed by washing with 0.1% TFA ACN, permitting re-use of the copolymer. RESULTS: Standard myoglobin and some practical protein samples from a biochemistry lab spiked with different concentrations of SDS were successfully cleaned up using this Os copolymer for LC/MS analyses. Up to 0.2% (w/v %) of SDS can be successfully removed from those protein samples. CONCLUSIONS: This Os-complexed copolymer provides a new alternative for quick cleanup of SDS from protein samples, and can serve as a new class of metal complex based anion exchanger for protein purification. PMID- 26864523 TI - Dissociation of trivalent metal ion (Al(3+), Ga(3+), In(3+) and Rh(3+))--peptide complexes under electron capture dissociation conditions. AB - RATIONALE: The electron capture dissociation (ECD) of proteins/peptides is affected by the nature of charge carrier. It has been reported that transition metal ions could tune the ECD pathway of peptides. To further explore the charge carrier effect of metal ions, ECD of peptides adducted with trivalent transition metal ions, including group IIIB (Al(3+), Ga(3+), and In(3+) ) and Rh(3+), were investigated and compared with that of the lanthanide ion (Ln(3+)). METHODS: Bradykinin-derived peptides were used as model peptides to probe the dissociation pathways. The ECD experiments were performed on a Bruker APEX III 4.7T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. RESULTS: Typical c /z-ions with and without metal ions were observed in the ECD of peptides adducted with Group IIIB metal ions as charge carriers. Connection of non-metalated c-ions and metalated z-ions at the position of the serine residue indicated that serine is one of the binding sites of the metal ion on the model peptides. Typical slow heating ions, including metalated a-/b-ions and non-metalated y-ions, were generated in ECD of Rh(3+) -adducted peptides. CONCLUSIONS: Based on the experimental results, it is proposed that (i) for Group IIIB metal ion-peptide complexes, the incoming electron is captured by the proton in the salt-bridge structures of precursor ions; (ii) for Rh(3+) -peptide complexes, the incoming electron is captured by the metal ion due to the formation of charge-solvated precursor ions formed through arginine residue-metal coordination. Our results indicate that the heterogeneity of precursor ions plays an important role for the ECD of metalated peptides. PMID- 26864524 TI - Impact of tissue surface properties on the desorption electrospray ionization imaging of organic acids in grapevine stem. AB - RATIONALE: Desorption electrospray ionization (DESI) imaging is a fast analytical technique used to assess spatially resolved biological processes over unmodified sample surfaces. Although DESI profiling experiments have demonstrated that the properties of the sample surface significantly affect the outcomes of DESI analyses, the potential implications of these phenomena in imaging applications have not yet been explored extensively. METHODS: The distribution of endogenous and exogenous organic acids in pith and out pith region of grapevine stems was investigated by using DESI imaging, ion chromatography and direct infusion methods. Several common normalization strategies to account for the surface effect, including TIC normalization, addition of the internal standard in the spray solvent and deposition of the standard over the sample surface, were critically evaluated. RESULTS: DESI imaging results show that, in our case, the measured distributions of these small organic acids are not consistent with their 'true' localizations within the tissues. Furthermore, our results indicate that the common normalization strategies are not able to completely compensate for the observed surface effect. CONCLUSIONS: Variations in the tissue surface properties across the tissue sample can greatly affect the semi-quantitative detection of organic acids. Attention should be paid when interpreting DESI imaging results and an independent analytical validation step is important in untargeted DESI imaging investigations. PMID- 26864525 TI - Covalent adducts of melphalan with free amino acids and a model peptide studied by liquid chromatography/tandem mass spectrometry. AB - RATIONALE: Melphalan is a frequently used chemotherapeutical agent for the treatment of myeloma, breast cancer, ovarian cancer and sarcoma of soft tissue. A good knowledge of the reactivity of the drug toward the different amino acids, e.g. covalent adduct formation, is crucial for the understanding of its activity and side effects during cancer treatment. METHODS: The reactivity of melphalan and sites of adduct formation were studied by in vitro incubation of melphalan with free amino acids and glutathione as a model peptide. The formed covalent adducts were investigated using ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) using a triple-quadrupole instrument. Accurate mass measurements for the confirmation of characteristic product ions were performed on a quadrupole time-of-flight (QTOF) mass spectrometer. RESULTS: The incubation of melphalan with different classes of amino acids resulted in the formation of adducts on the amino and carboxyl termini, as well as adduct formation in the reactive side chains of Cys, Met, Tyr, His, Lys, Asp and Glu. All these melphalan adducts could be identified by their characteristic collision induced dissociation (CID) product ion patterns. CONCLUSIONS: The present study demonstrates the reactivity of melphalan towards the functional groups of amino acids. The different alkylation site products show distinctive fragmentation patterns, which enable a fast identification of the different melphalan adducts. This study is a first important step towards a better understanding of the adduct formation in more complex molecules, e.g. peptides and proteins. PMID- 26864526 TI - Differentiating samples and experimental protocols by direct comparison of tandem mass spectra. AB - RATIONALE: Peptide tandem mass spectra can be analyzed by a number of means. They can be compared against predicted spectra of peptides derived from genome sequences, compared against previously acquired and identified spectra, or - sometimes - sequenced de novo. We recently introduced another method which compares spectra between liquid chromatography/tandem mass spectrometry (LC/MS/MS) datasets to determine the shared spectral content, and demonstrated how this can be applied in a molecular phylogenetic study using sera from human and non-human primates. We will here explore if such a method have other, serendipitous uses. METHODS: We used the existing compareMS2 algorithm without modification on a diverse set of experiments. RESULTS: First we conducted a small phylogenetic study, using (mammalian) bone samples to study old material, and human pathogens aiming to distinguish clinically important strains. Although not as straightforward as primate sera analysis, the method shows significant promise for all these applications. We also used the algorithm to compare 24 different protocols for extraction of proteins from muscle tissue. The results provided useful information in comparing protocols. Finally, we applied compareMS2 aiming for quality control of two traceable protein reference standards (troponin) used in clinical chemistry assays, by analysing the effect of storage conditions. CONCLUSIONS: The results illustrate a broad applicability of the metric based on shared tandem mass spectra between LC/MS/MS datasets for analysing protein digests in different types of experiments. There is no reason to assume that our instance of this method is optimal in any of these situations, as it makes limited or no use of accurate mass and chromatographic retention time. We propose that with further improvement and refinement, this type of analysis can be applied as a simple but informative first step in many pipelines for bottom-up tandem mass spectrometry data analysis in proteomics and other fields, comparing or analysing large numbers of samples or datasets. PMID- 26864527 TI - A hybrid strategy using global analysis of oxidized fatty acids and bioconversion by Bacillus circulans. AB - RATIONALE: Targeted oxidized fatty acid analysis has been widely used to understand the roles of fatty acids in the development of diseases. However, because of the extensive structural diversity of fatty acids, it is considered that unknown lipid metabolites will remain undetected. Here, to discover and identify unknown lipid metabolites in biological samples, a global analytical system and a method of synthesizing lipid standards were investigated. METHODS: Oxidized fatty acids in mouse lung tissues were extracted using mixed-mode spin columns. Separation was achieved via ultra-high-performance liquid chromatography, mass spectrometric (MS) analysis was conducted in full scan mode using a Q Exactive Plus instrument equipped with an electrospray ionization probe, and structure analysis was carried out by high-resolution data-dependent tandem mass spectrometry (dd-MS(2)). In addition, lipid standards, which are not commercially available, were synthesized by bioconversion using Bacillus circulans. RESULTS: Oxidized fatty acids in mouse lung tissues were analyzed by high-resolution accurate-mass analysis, and multiple unknown molecules were discovered and tentatively identified using high-resolution dd-MS(2). Among these molecules, 21-hydroxydocosahexaenoic acid (21-HDoHE) and 22-HDoHE, which are not commercially available, were synthesized by bioconversion. By comparing the exact masses, retention times, and characteristic fragment ions of the synthesized standards, 21-HDoHE and 22-HDoHE were definitively identified in the mouse lung tissue. CONCLUSIONS: Our strategy of global analysis and bioconversion can be used for the discovery and identification of unknown lipid molecules. PMID- 26864528 TI - Differentiation of cyclic tertiary amine cathinone derivatives by product ion electron ionization mass spectrometry. AB - RATIONALE: A number of synthetic cathinones (aminoketones, 'bath salts') are tertiary amines containing a cyclic amino group, most commonly pyrrolidine. These totally synthetic compounds can be prepared in a number of regioisomeric designer modifications and many of these can yield isomeric major fragment ions in electron ionization mass spectrometry (EI-MS). METHODS: A series of regioisomeric cyclic tertiary amines were prepared and evaluated in EI-MS and MS/MS product ion experiments. The cyclic amines azetidine, pyrrolidine, piperidine and azepane were incorporated into a series of aminoketones related to the cathinone derivative drug of abuse known as MDPV. Deuterium labeling in both the cyclic amine and alkyl side chain allowed for the confirmation of the structure for the major product ions formed from the EI-MS iminium cation base peaks. RESULTS: These iminium cation base peaks show characteristic product ion spectra which allow differentiation of the ring and side-chain portions of the structure. The small alkyl side chains favor ring fragmentation in the formation of the major product ions. The higher side-chain homologues appear to promote product ion formation by side-chain fragmentation. Both side-chain and ring fragmentation yield a mixture of product ions in the piperidine and azepane series. CONCLUSIONS: Product ion fragmentation provides useful data for differentiation of cyclic tertiary amine iminium cations from cathinone derivative drugs of abuse. Regioisomeric iminium cations of equal mass yield characteristic product ions for the alkyl side-chain homologues of azetidine, pyrrolidine, piperidine and azepane cyclic amines. PMID- 26864529 TI - A simple heated-capillary modification improves the analysis of non-covalent complexes by Z-spray electrospray ionization. AB - RATIONALE: The observation of intact non-covalent complexes by electrospray ionization mass spectrometry (ESI-MS) hinges on the ability to minimize in-source activation processes that take place during analyte desolvation. We explored the merits of replacing the sampling cone of a standard Z-spray source with a heated capillary that makes the desolvation process slower and more gradual. We employed well-characterized protein-RNA, RNA-RNA, and DNA-DNA assemblies to compare the alternative configurations. METHODS: Mass analysis evaluated the integrity of the complexes, whereas traveling wave ion mobility experiments assessed the stability of biomolecular structure. Analyses were performed back-to-back on the same samples on a Synapt G2 HDMS equipped with either the standard sampling cone or the heated-capillary apparatus. In each configuration, the source/capillary temperature was varied in controlled fashion, while keeping all other desolvation parameters constant to monitor the in-source dissociation of selected DNA duplexes. Ion mobility data were obtained from the same precursor by using the alternative configurations under the same settings. RESULTS: Monitoring the percentage of associated complex demonstrated that the heated capillary provided softer desolvation that was more conducive to the detection of intact non covalent interactions. This configuration failed to produce complete dissociation of 14 bp and 24 bp duplexes, even when the source/capillary temperature was increased well above their solution melting points. Analyzed by IMS-MS, a selected construct displayed just one conformation with the heated capillary, but two with the standard sampling cone. CONCLUSIONS: The heated capillary minimizes in-source activation processes that can lead to unintended dissociation of complexes and perturbation of biomolecular structure, which rely on the integrity of non-covalent interactions. This effect can be attributed to the attenuation of the supersonic expansion typical of the Z-spray geometry and the greater ability to control the energy imparted to the system. This hardware modification will be expected to benefit the analysis of biomolecular structure performed on this particular instrumental platform. PMID- 26864530 TI - Improved removal of volatile organic compounds for laser-based spectroscopy of water isotopes. AB - RATIONALE: Volatile organic compounds (VOCs) such as methanol and ethanol in water extracted from plants cause spectral interference in isotope ratio infrared spectroscopy (IRIS). This contamination degrades the accuracy of measurements, limiting the use of IRIS. In response, this study presents a new decontamination method of VOCs for enhanced IRIS measurements. METHODS: The isotopic compositions of water from laboratory-made and field-collected plant samples pre- and post treatment were analyzed using IRIS. Traditional treatment methods of activated charcoal and commercial pre-combustion systems (MCM) were compared with our new treatment method that implements solid-phase extraction (SPE). The absolute concentrations of contaminants pre- and post-treatment were determined using (1)H and (13)C nuclear magnetic resonance to assess the effectiveness of the different treatments. RESULTS: SPE removes an average of 86.7% and 78.8% ethanol and methanol, respectively, significantly reducing spectral interference. SPE reduces errors to within instrumental noise for both ethanol and methanol at concentrations found in nature (<3.0% and 0.08%, respectively). Activated charcoal minimally affected alcohol concentrations. MCM significantly worsened ethanol-contaminated water isotope measurements by producing primary alcohol oxidation products such as formic acid, another compound that interferes with IRIS absorption. CONCLUSIONS: SPE is an effective, low-cost method for eliminating errors in ethanol-contaminated samples. For samples where methanol is prevalent, combining SPE and MCM is more effective than the use of SPE alone. Hence, SPE treatment alone or in conjunction with MCM is recommended as an effective pre-analysis purification method for water extracted from plants. PMID- 26864531 TI - The jasmonate-responsive AaMYC2 transcription factor positively regulates artemisinin biosynthesis in Artemisia annua. AB - The plant Artemisia annua is well known due to the production of artemisinin, a sesquiterpene lactone that is widely used in malaria treatment. Phytohormones play important roles in plant secondary metabolism, such as jasmonic acid (JA), which can induce artemisinin biosynthesis in A. annua. Nevertheless, the JA inducing mechanism remains poorly understood. The expression of gene AaMYC2 was rapidly induced by JA and AaMYC2 binds the G-box-like motifs within the promoters of gene CYP71AV1 and DBR2, which are key structural genes in the artemisinin biosynthetic pathway. Overexpression of AaMYC2 in A. annua significantly activated the transcript levels of CYP71AV1 and DBR2, which resulted in an increased artemisinin content. By contrast, artemisinin content was reduced in the RNAi transgenic A. annua plants in which the expression of AaMYC2 was suppressed. Meanwhile, the RNAi transgenic A. annua plants showed lower sensitivity to methyl jasmonate treatment than the wild-type plants. These results demonstrate that AaMYC2 is a positive regulator of artemisinin biosynthesis and is of great value in genetic engineering of A. annua for increased artemisinin production. PMID- 26864533 TI - Spontaneous retroperitoneal hematoma in a patient under anticoagulant agents presenting as upper gastrointestinal bleeding. AB - We present the case of a 44-year-old woman with past history of repeated miscarriage and Budd-Chiari syndrome secondary to primary myelofibrosis. Because of this she was under treatment with oral anticoagulant agents. The patient was admitted in hospital as she presented with gastrointestinal bleeding (melena), asthenia and progressive anemia. In an initial upper endoscopy an extrinsic duodenal compression associated with an ulcer on the posterior face of the first portion of duodenum and upper duodenal knee was observed. In the following days a huge spontaneous retroperitoneal hematoma due to anticoagulation was diagnosed by computed tomography. This was treated with a percutaneous drainage and withdrawal of the antithrombotic drugs. The evolution of the patient was initially satisfactory but she suffered subclavian and jugular vein thrombosis, and reintroduction of anticoagulant agents at the lowest therapeutic doses was required. PMID- 26864532 TI - Regulation of UVR8 photoreceptor dimer/monomer photo-equilibrium in Arabidopsis plants grown under photoperiodic conditions. AB - The UV RESISTANCE LOCUS 8 (UVR8) photoreceptor specifically mediates photomorphogenic responses to UV-B. Photoreception induces dissociation of dimeric UVR8 into monomers to initiate responses. However, the regulation of dimer/monomer status in plants growing under photoperiodic conditions has not been examined. Here we show that UVR8 establishes a dimer/monomer photo equilibrium in plants growing in diurnal photoperiods in both controlled environments and natural daylight. The photo-equilibrium is determined by the relative rates of photoreception and dark-reversion to the dimer. Experiments with mutants in REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 show that these proteins are crucial in regulating the photo-equilibrium because they promote reversion to the dimer. In plants growing in daylight, the UVR8 photo equilibrium is most strongly correlated with low ambient fluence rates of UV-B (up to 1.5 MUmol m(-2) s(-1) ), rather than higher fluence rates or the amount of photosynthetically active radiation. In addition, the rate of reversion of monomer to dimer is reduced at lower temperatures, promoting an increase in the relative level of monomer at approximately 8-10 degrees C. Thus, UVR8 does not behave like a simple UV-B switch under photoperiodic growth conditions but establishes a dimer/monomer photo-equilibrium that is regulated by UV-B and also influenced by temperature. PMID- 26864535 TI - Erratum to: One-Dimensional Haemodynamic Modeling and Wave Dynamics in the Entire Adult Circulation. PMID- 26864534 TI - Post-traumatic stress disorder and alcohol misuse: comorbidity in UK military personnel. AB - AIMS: To determine the prevalence of comorbid probable post-traumatic stress disorder and alcohol misuse in a UK military cohort study and to determine the level of co-occurrence between these disorders; further aims were to investigate the association between alcohol misuse and the different PTSD symptom clusters, and to assess what factors are associated with probable PTSD in participants with alcohol misuse. METHODS: Data from 9984 participants of Phase 2 of the health and well-being survey of serving and ex-serving members of the UK Armed Forces were assessed for probable PTSD and alcohol misuse using the PTSD checklist (PCL-C) and the alcohol use disorders identification test (AUDIT), respectively. RESULTS: 1.8 % [95 % confidence interval (CI) 1.5-2.1] of the sample met the criteria for both PTSD and alcohol misuse. All three symptom clusters of PTSD were significantly associated with alcohol misuse, with similar odds ranging from 2.46 to 2.85. Factors associated with probable PTSD in individuals reporting alcohol misuse were age [ages 30-34 (years): OR 2.51, 95 % CI 1.15-5.49; ages 40-44 years: OR 2.77, 95 % CI 1.18-6.47], officer rank (OR 0.36, 95 % CI 0.16-0.85), being in a combat role in parent unit (OR 1.99, 95 % CI 1.20-3.31) and common mental disorder (CMD) (OR 21.56, 95 % CI 12.00-38.74). CONCLUSIONS: This study provides strong evidence that PTSD and alcohol misuse are often co-occurring. CMD was highly associated with probable PTSD in individuals with alcohol misuse. PMID- 26864536 TI - Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices. AB - A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence. PMID- 26864537 TI - A Universal Delivery System for Percutaneous Heart Valve Implantation. AB - Transcatheter heart valve implantation is an emerging technology and an alternative to surgical valve replacement. Most existing systems consist of valves sewn into balloon-expandable stents with a delivery catheter functioning with the specific valve only. The aim of this study was to develop a universally applicable delivery system (DS) for plane stents, valves sewn into both balloon expandable and self-expandable stents and feasible for use with different access routes. A DS was designed and manufactured in five different diameters. The requirements were derived from the implants, the implantation technique and the cardiovascular geometry of the experimental sheep. The combination of a self expandable Nitinol stent and a jugular access point represented the major challenge as both flexibility and rigidity of the DS were required. To fulfill these contradicting mechanical properties the sheaths were comprised of a soft outer polymer tube with a stainless steel coiled spring inside. Tissue-engineered and pericardial pulmonary valves were implanted. Also polymeric and balloon expandable stents were delivered to various positions in the vascular system. The initial success rate was 70.5%. After refinement of the DS, a success rate of 83.3% was achieved with the remaining failed implantations resulting from inadequate sizes of the prostheses. PMID- 26864538 TI - Biofidelity Evaluation of a Prototype Hybrid III 6 Year-Old ATD Lower Extremity. AB - Incomplete instrumentation and a lack of biofidelity in the extremities of the 6 year-old anthropomorphic test device (ATD) pose challenges when studying regions of the body known to interact with the vehicle interior. This study sought to compare a prototype Hybrid III 6 year-old ATD leg (ATD-LE), with a more biofidelic ankle and tibia load cell, to previously collected child volunteer data and to the current Hybrid III 6 year-old ATD (HIII). Anthropometry, range of motion (ROM), and stiffness measurements were taken, along with a dynamic evaluation of the ATD-LE using knee-bolster airbag (KBA) test scenarios. Anthropometry values were similar in eight of twelve measurements. Total ankle ROM was improved in the ATD-LE with no bumper compared to the HIII. The highest tibia moments and tibia index values were recorded in KBA scenarios when the toes were positioned in contact with the dashboard prior to airbag deployment, forcing the ankle into axial loading and dorsiflexion. While improvements in the biofidelity of the ATD-LE are still necessary, the results of this study are encouraging. Continued advancement of the 6 year-old ATD ankle is necessary to provide a tool to directly study the behavior of the leg during a motor vehicle crash. PMID- 26864539 TI - Petrol exposure and DNA integrity of peripheral lymphocytes. AB - PURPOSE: To determine the effect of petrol exposure on DNA integrity in peripheral blood lymphocytes among petrol attendants and a non-exposed comparison population. METHODS: This cross-sectional study included 101 fuel station employees and 50 office-based non-exposed workers in Durban, South Africa. Participants were interviewed using a validated questionnaire. Genomic DNA was extracted from peripheral lymphocytes for the benzo(a)pyrene diol epoxide (BPDE) DNA adduct assay (ELISA), and DNA damage was determined using the comet assay and reported as percentage tail DNA. RESULTS: The exposed (n = 101) and non-exposed participants (n = 50) varied with regard to age, housing, smoking, and proximity to industry and petrol stations. Among the exposed, the mean duration of employment in the fuel industry was 5.8 years (SD = 4.6), and among those pumping fuel (n = 75), the mean metric tons of petrol pumped in the past 12 months per worker was 199.2 (SD = 88.9). The mean percentage tail DNA varied significantly between exposed and non-exposed groups: 23.8 % (SD = 13.3) and 8.1 % (SD = 1.8) (p < 0.01), respectively. A significant difference existed between the groups for BPDE-DNA adducts: 30.0 ng/ml (SD = 12.7) and 18.1 ng/ml (SD = 18.2) (p < 0.0001), respectively. Regression models, adjusting for cigarette smoking, age, and sex, showed a 16.5 greater percentage tail DNA among the exposed compared to non exposed (95 % CI 11.8-21.1 %), while the exposed group had a 12.9 ng/ml greater increase in BPDE-DNA adducts has compared to the unexposed (95 % CI 7.2-18.7 ng/ml). Cigarette smoking resulted in almost a 3.5 % increase in percentage tail DNA. CONCLUSION: Our study adds to the literature that long-term, low-dose exposure to vehicular fuels is likely to result in altered DNA integrity and genotoxicity among petrol attendants. These results strengthen the case that these workers must be afforded appropriate protection to prevent serious adverse outcomes. PMID- 26864541 TI - A Parametric Computational Study of the Impact of Non-circular Configurations on Bioprosthetic Heart Valve Leaflet Deformations and Stresses: Possible Implications for Transcatheter Heart Valves. AB - Although generally manufactured as circular devices with symmetric leaflets, transcatheter heart valves can become non-circular post-implantation, the impact of which on the long-term durability of the device is unclear. We investigated the effects of five non-circular (EllipMajor, EllipMinor, D-Shape, TriVertex, TriSides) annular configurations on valve leaflet stresses and valve leaflet deformations through finite element analysis. The highest in-plane principal stresses and strains were observed under an elliptical configuration with an aspect ratio of 1.25 where one of the commissures was on the minor axis of the ellipse. In this elliptical configuration (EllipMinor), the maximum principal stress increased 218% and the maximum principal strain increased 80% as compared with those in the circular configuration, and occurred along the free edge of the leaflet whose commissures were not on the minor axis (i.e., the "stretched" leaflet). The D-Shape configuration was similar to this elliptical configuration, with the degree to which the leaflets were stretched or sagging being less than the EllipMinor configuration. The TriVertex and TriSides configurations had similar leaflet deformation patterns in all three leaflets and similar to the Circular configuration. In the D-Shape, TriVertex, and TriSides configurations, the maximum principal stress was located near the commissures similar to the Circular configuration. In the EllipMinor and EllipMajor configurations, the maximum principal stress occurred near the center of the free edge of the "stretched" leaflets. These results further affirm recommendations by the International Standards Organization (ISO) that pre-clinical testing should consider non-circular configurations for transcatheter valve durability testing. PMID- 26864540 TI - Chemotyping the distribution of vitamin D metabolites in human serum. AB - Most studies examining the relationships between vitamin D and disease or health focus on the main 25-hydroxyvitamin D3 (25(OH)D3) metabolite, thus potentially overlooking contributions and dynamic effects of other vitamin D metabolites, the crucial roles of several of which have been previously demonstrated. The ideal assay would determine all relevant high and low-abundant vitamin D species simultaneously. We describe a sensitive quantitative assay for determining the chemotypes of vitamin D metabolites from serum after derivatisation and ultra high performance liquid chromatography-electrospray ionisation-tandem mass spectrometry (UHPLC-ESI-MS/MS). We performed a validation according to the 'FDA Guidance for Industry Bioanalytical Method Validation'. The proof-of-concept of the method was then demonstrated by following the metabolite concentrations in patients with chronic liver diseases (CLD) during the course of a vitamin D supplementation study. The new quantitative profiling assay provided highly sensitive, precise and accurate chemotypes of the vitamin D metabolic process rather than the usually determined 25(OH)D3 concentrations. PMID- 26864542 TI - Stereopositional Outcome in the Packing of Dissimilar Aromatics in Designed beta Hairpins. AB - A popular strategy in the de novo design of stable beta-sheet structures for various biomedical applications is the incorporation of aromatic pairs at the non hydrogen-bonding (NHB) position. However, it is important to explicitly understand how aryl pair packing at the NHB region is coordinated with backbone structural rearrangements, and to delineate the benefits and drawbacks associated with stereopositional choice of dissimilar aromatic pairs. Here, we probe the consequences of flipped Trp/Tyr pairs by using engineered permutants at the NHB position of dodecapeptide beta-hairpins, proximal and distal to the turn. Extensive conformational analysis of these peptides using NMR and CD spectroscopy reveal that a classic Edge-to-Face and Face-to-Edge geometry at the proximal and distal aromatic pairs, respectively, in YW-WY, is the most stabilizing. Such a preferred packing geometry in YW-WY results in a highly twisted beta-sheet backbone, with Trp always providing a 'Face' orientation to its dissimilar aromatic partner Tyr. Flipping the proximal and/or distal aromatic pair distorts the ideal T-shaped geometry, and results in alternate aryl arrangements that can adversely affect strand twist and beta-sheet stability. Our study reveals the existence of a strong stereopositional influence on the packing of dissimilar aromatic pairs. Our findings highlight the importance of modeling physical interaction forces while designing protein and peptide structures for functional applications. PMID- 26864545 TI - Fulfilment of administrative and professional organisational obligations and nurses' customer-oriented behaviours. AB - AIM: The aim of the study was to examine the relationship between the perceived quality of organisational exchange and nurses' customer-oriented behaviours. BACKGROUND: Hospitals face increasing competitive market conditions. Registered nurses interact closely with patients and therefore play an important front office role towards patients. METHODS: A cross-sectional study was conducted. Registered nurses (n = 151) of a Belgian hospital received a questionnaire to assess the fulfilment of administrative and professional organisational obligations and their customer-oriented behaviours. RESULTS: We found a positive relationship between psychological contract fulfilment and nurses' customer oriented behaviours. More precisely administrative and professional psychological contract fulfilment relates significantly to nurses' service delivery and external representation. In case of internal influence only administrative psychological contract fulfilment was significantly related. CONCLUSIONS: Nurses' perceptions of the fulfilment of administrative and professional obligations are important to their customer-oriented behaviours. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers must be aware of the impact of fulfilling both administrative and professional obligations of registered nurses in order to optimise their customer-oriented behaviours. PMID- 26864543 TI - The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies. AB - The safety and tolerability of vortioxetine in adults with major depressive disorder was assessed. Tolerability was based on the nature, incidence and severity of treatment-emergent adverse events (TEAEs) during acute (6/8) week treatment in 11 randomized, double-blind placebo-controlled short-term studies in major depressive disorder: six with an active reference. Symptoms following discontinuation were assessed through the Discontinuation-Emergent Signs and Symptoms checklist in three studies. Long-term (?52 weeks) tolerability was evaluated in five open-label extension studies. Patients (n =5701) were acutely treated with either placebo (n=1817), vortioxetine (5-20mg/day; n=3018), venlafaxine XR (225mg/day; n=113) or duloxetine (60mg/day; n=753). The withdrawal rate due to TEAEs during treatment with vortioxetine (5-20mg/day) was 4.5-7.8%, compared with placebo (3.6%), venlafaxine XR (14.2%) or duloxetine (8.8%). Common TEAEs (incidence ?5% and >2 * placebo) with vortioxetine (5-20mg/day) were nausea (20.9-31.2%) and vomiting (2.9-6.5%). For vortioxetine (5-20mg/day), the incidence of TEAEs associated with insomnia was 2.0-5.1% versus 4.0% for placebo, and with sexual dysfunction 1.6-1.8% versus 1.0% for placebo. Discontinuation symptoms as assessed by the mean Discontinuation-Emergent Signs and Symptoms total score after abrupt discontinuation were comparable to placebo in the first and second week. Vortioxetine had no effect relative to placebo on clinical laboratory parameters, body weight, heart rate or blood pressure. Vortioxetine showed no clinically relevant effect on ECG parameters, including the QTcF interval. In long-term treatment, no new types of TEAEs were seen; the mean weight gain was 0.7-0.8kg. Thus, vortioxetine (5-20mg/day) appears safe and generally well tolerated in the treatment of major depressive disorder. PMID- 26864547 TI - StatNet Electroencephalogram: A Fast and Reliable Option to Diagnose Nonconvulsive Status Epilepticus in Emergency Setting. AB - BACKGROUND: The StatNet electrode set is a system that can be applied by a non electroencephalogram (EEG) technologist after minimal training. The primary objectives of this study are to assess the quality and reliability of the StatNet recordings in comparison to the conventional EEG. METHODS: Over 10 months, 19 patients with suspected nonconvulsive status epilepticus were included from university hospital emergency settings. Each patient received a StatNet EEG by a trained epilepsy fellow and a conventional EEG by registered technologists. We compared the studies in a blinded fashion, for the timeframe from EEG order to the setup time, start of acquisition, amount of artifact, and detection of abnormalities. The nonparametric Mann-Whitney two-sample t test was used for comparisons. The kappa score was used to assess reliability. RESULTS: Mean age of patients was 61+/-16.3 (25-93) years. The inter-observer agreement for detection of abnormal findings was 0.83 for StatNet and 0.75 for conventional EEG. Nonconvulsive status epilepticus was detected in 10% (2/19) in both studies. The delay from the time of EEG requisition to acquisition was shorter in the StatNet (22.4+/-2.5 minutes) than the conventional EEG (217.7+/-44.6 minutes; p<0.0001). The setup time was also shorter in the StatNet (9.9+/-0.8 minutes) compared with the conventional EEG (17.8+/-0.8 minutes; p<0.0001). There was no difference in the percentage of artifact duration between the two studies (p=0.89). CONCLUSION: This study demonstrates that StatNet EEG is a practical and reliable tool in the emergency setting, which reduces the delay of testing compared with conventional EEG, without significant compromise of study quality. PMID- 26864546 TI - Small interfering RNA pathway modulates persistent infection of a plant virus in its insect vector. AB - Plant reoviruses, rhabdoviruses, tospoviruses, and tenuiviruses are transmitted by insect vectors in a persistent-propagative manner. How such persistent infection of plant viruses in insect vectors is established and maintained remains poorly understood. In this study, we used rice gall dwarf virus (RGDV), a plant reovirus, and its main vector leafhopper Recilia dorsalis as a virus-insect system to determine how the small interference (siRNA) pathway modulates persistent infection of a plant virus in its insect vector. We showed that a conserved siRNA antiviral response was triggered by the persistent replication of RGDV in cultured leafhopper cells and in intact insects, by appearance of virus specific siRNAs, primarily 21-nt long, and the increased expression of siRNA pathway core components Dicer-2 and Argonaute-2. Silencing of Dicer-2 using RNA interference strongly suppressed production of virus-specific siRNAs, promoted viral accumulation, and caused cytopathological changes in vitro and in vivo. When the viral accumulation level rose above a certain threshold of viral genome copy (1.32 * 10(14) copies/MUg insect RNA), the infection of the leafhopper by RGDV was lethal rather than persistent. Taken together, our results revealed a new finding that the siRNA pathway in insect vector can modulate persistent infection of plant viruses. PMID- 26864548 TI - ERp57 as a novel cellular factor controlling prion protein biosynthesis: Therapeutic potential of protein disulfide isomerases. AB - Disturbance of endoplasmic reticulum (ER) proteostasis is observed in Prion related disorders (PrDs). The protein disulfide isomerase ERp57 is a stress responsive ER chaperone up-regulated in the brain of Creutzfeldt-Jakob disease patients. However, the actual role of ERp57 in prion protein (PrP) biogenesis and the ER stress response remained poorly defined. We have recently addressed this question using gain- and loss-of-function approaches in vitro and animal models, observing that ERp57 regulates steady-state levels of PrP. Our results revealed that ERp57 modulates the biosynthesis and maturation of PrP but, surprisingly, does not contribute to the global cellular reaction against ER stress in neurons. Here we discuss the relevance of ERp57 as a possible therapeutic target in PrDs and other protein misfolding disorders. PMID- 26864549 TI - Biological Properties of Plant-Derived Alkylresorcinols: Mini-Review. AB - Alkylresorcinols are compounds which belong to the family of phenolic lipids, and are usually found in numerous biological species. In the particular case of higher plants, alkylresorcinols have been found in various counterparts with chains of thirteen to twenty-seven carbon atoms containing several saturations. Due to the demonstrated antimicrobial properties of many naturally occurring members of the alkylresorcinols family, it is possible to conclude that these compounds act as defensive agents in plants. Previous studies led to the isolation and identification of 5-alkylresorcinols that cleave DNA. Additionally, in the literature, there are several other biological effects attributed to some resorcinol derivatives, namely, cytotoxic, anticarcinogenic, antiproliferative, antileishmanial and antioxidant properties. This mini-review intends to outline the biological activities of the most relevant alkylresorcinols isolated from plants and to propose future directions for subsequent studies regarding the effective biological effects of this class of compounds. PMID- 26864550 TI - Cadmium-containing Quantum Dots: Current Perspectives on Their Application as Nanomedicine and Toxicity Concerns. AB - With unique optical properties and versatile surface chemistry, cadmium containing quantum dots (Cd-QDs) have attracted extensive attention for drug delivery in the field of biomedicine. However, Cd-QDs applications are currently restricted in cells and small animals due to their uncertain biological fate and potential toxicity. Consequently, the long-term fate of Cd-QDs and their interaction with biological systems need to be explored for the development of the clinical applications of Cd-QDs as nanomedicines. This review succinctly described recent progress in functionalized Cd-QDs for the design as multifunctional drug delivery system and advanced findings on the interactions of Cd-QDs with biological systems at the level of living systems, cells and biomacromolecules. This knowledge could provide suggestions to improve the delivery performance and biocompatibility of Cd-QDs as well as better understand the potential side effects of Cd-QDs in in vivo applications. In addition, attention was laid on exploring the similarities and discrepancy of their toxicological results at the three levels to comprehensively interpret the potential carcinogenicity of Cd-QDs and deeply understand the associated mechanism. PMID- 26864551 TI - Novel Drugs Targeting the c-Ring of the F1FO-ATP Synthase. AB - Increasing evidence highlights the role of the ATP synthase/hydrolase, also known as F1FO-complex, as key molecular and enzymatic switch between cell life and death, thus increasing the enzyme attractiveness as drug target in pharmacology. Being inhibition of ATP production usually linked to antiproliferative properties, drugs targeting the enzyme complex have been mainly considered to fight pathogen parasites and cancer. In recent years, a number of natural macrolides, produced by bacterial fermentation and structurally related to the classical enzyme inhibitor oligomycin, have been shown to bind to the membrane embedded FO sector and to inhibit the enzyme complex by an oligomycin-like mechanism, namely by interacting with the c-ring. Other than natural macrolide antibiotics, which display variegated inhibition power on different F1FO complexes, synthetic compounds from the diarylquinoline and organotin families also target the c-ring and strongly inhibit the enzyme. Bioinformatic insights address drug design to target FO subunits. Additionally, the possible modulation of the drug inhibition power, by amino acid substitutions or post-translational modifications of c-subunits, adds further interest to the target. The present survey on compounds targeting the c-ring and bi-directionally blocking the transmembrane proton flux which drives ATP synthesis/hydrolysis, discloses new therapeutic options to fight cancer and infections sustained by therapeutically recalcitrant microorganisms. Additionally, c-ring targeting compounds may constitute new tools to eradicate undesired biofilms and to address at the molecular level the therapy of mammalian diseases linked to mitochondrial dysfunctions. In summary, studies on the only partially known molecular interactions within the c-ring of the F1FO-complex may renew hope to counteract mammalian diseases. PMID- 26864552 TI - Synthesis and Biological Activities of Oxadiazole Derivatives: A Review. AB - Recently, there has been wide interest in compounds containing the oxadiazole scaffold because of their unique chemical structure and their broad spectrum of biological properties. This review provides readers with an overview of the main synthetic methodologies for oxadiazoles and of their broad spectrum of pharmacological activities such as, anti-microbial, anti-fungal activity, antiviral, anti-tubercular, anti-inflammatory, anti-convulsant, anti-angiogenic, anti-proliferative, analgesic, anti-oedema and in alzheimer activity, which were reported over the past years. PMID- 26864553 TI - Bioactive Compounds in Some Culinary Aromatic Herbs and Their Effects on Human Health. AB - Culinary herbs are herbaceous (leafy) plants that add flavour and colour to all types of meals. There is a wide variety of herbs that are used for culinary purposes worldwide, which are also recognized for their beneficial health effects, and thus have also been used in folk medicine. Besides their nutritional value herbs are rich in many phytochemical components with bioactive effects, thus improving human health. The aim of the present work was to make a general overview of some of these herbs, including their gastronomic usage, their chemical composition in bioactive components and their reported health effects. This work showed that the health effects are very diverse and differ according to the herb in question. However, some of the most frequently citted biological activities include antioxidant, antimicrobial, and antiviral effects. PMID- 26864555 TI - Natural Products with Antiangiogenic and Antivasculogenic Mimicry Activity. AB - Angiogenesis is indispensible for tumor growth and metastasis. Antiangiogenic therapy is now a validated major strategy in cancer clinic; several small molecule angiogenic inhibitors have been successfully translated into clinic for multiple cancer indications. In the past decade, many natural products with potent antiangiogenic activity were explored and the underlying molecular mechanisms were revealed. One important mechanism is the inhibition of one or several steps in VEGF/VFGFR signaling pathway. Other factors (bFGF, HIF-1alpha, NF-kappaB etc.) capable of regulating angiogenesis, are also down-regulated by some natural products. Moreover, some of the antiangiogenic natural products also significantly inhibit vasculogenic mimicry (VM), another important vessel recruitment avenue in cancer, by regulating the key signaling of VM formation including VE-cadherin, EphA2, and Nodal signaling. In this mini-review, we summarized the natural products with suppressive effect on tumor angiogenesis and VM according to their diverse molecular mechanisms, and discussed the major direction of future research in this field. PMID- 26864556 TI - Cyclic movement frequency is associated with muscle typology in athletes. AB - There is a continuing research interest in the muscle fiber type composition (MFTC) of athletes. Recently, muscle carnosine quantification by proton magnetic resonance spectroscopy (1 H-MRS) was developed as a new non-invasive method to estimate MFTC. This cross-sectional study aims to better understand estimated MFTC in relation to (a) different disciplines within one sport; (b) cyclic sport exercise characteristics; (c) within-athlete variability; and (d) athlete level. A total of 111 elite athletes (74 runners, 7 triathletes, 11 swimmers, 14 cyclists and 5 kayakers) and 188 controls were recruited to measure muscle carnosine in gastrocnemius and deltoid muscle by 1 H-MRS. Within sport disciplines, athletes were divided into subgroups (sprint-, intermediate-, and endurance-type). The controls were used as reference population to allow expression of the athletes' data as Z-scores. Within different sports, endurance type athletes systematically showed the lowest Z-score compared to sprint-type athletes, with intermediate-type athletes always situated in between. Across the different sports disciplines, carnosine content showed the strongest significant correlation with cyclic movement frequency (R = 0.86, P = 0.001). Both within and between different cyclic sports, estimated MFTC was divergent between sprint- and endurance-type athletes. Cyclic movement frequency, rather than exercise duration came out as the most determining factor for the optimal estimated MFTC in elite athletes. PMID- 26864557 TI - Description and prediction of the income status of borderline patients over 10 years of prospective follow-up. AB - BACKGROUND: Research shows that individuals suffering from borderline personality disorder are economically disadvantaged, but longitudinal data is lacking. AIM: This study examined the income of borderline personality disorder (BPD) patients and axis II comparison subjects over 10 years of follow-up and assessed predictors of income among BPD patients. METHOD: Data on income was obtained for 264 BPD patients and 63 axis II comparison subjects at 6-year follow-up and for surviving patients at five follow-up waves. Baseline and time-varying predictors of income were assessed using information from interviews and self-report measures. RESULTS: Regardless of diagnosis, a greater proportion of people shifted into the higher income groups over time. Being in a higher income group was more likely to happen and happened more rapidly for axis II comparison subjects than for BPD patients. Results regarding the BPD patients indicated that childhood emotional, verbal and/or physical abuse were associated with a greater likelihood of being in a lower income group, whereas years of education and a higher IQ were associated with a greater likelihood of being in a higher income group. CONCLUSION: Borderline personality disorder (BPD) patients show enduring lowered economic functioning. Their economic functioning seems to be negatively affected by childhood emotional, verbal and/or physical abuse but positively affected by years of education and IQ. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864558 TI - Design and Synthesis of Highly Active Peroxisome Proliferator-Activated Receptor (PPAR) beta/delta Inverse Agonists with Prolonged Cellular Activity. AB - Based on 3-(((4-(hexylamino)-2-methoxyphenyl)amino)sulfonyl)-2 thiophenecarboxylic acid methyl ester (ST247, compound 2), a recently described peroxisome proliferator-activated receptor (PPAR)beta/delta-selective inverse agonist, we designed and synthesized a series of structurally related ligands. The structural modifications presented herein ultimately resulted in a series of ligands that display increased cellular activity relative to 2. Moreover, with methyl 3-(N-(2-(2-ethoxyethoxy)-4-(hexylamino)phenyl)sulfamoyl)thiophene-2 carboxylate (PT-S264, compound 9 u), biologically relevant plasma concentrations in mice were achieved. The compounds presented in this study will provide useful novel tools for future investigations addressing the role of PPARbeta/delta in physiological and pathophysiological processes. PMID- 26864560 TI - Abstracts of the 21st Congress of the Spanish Society for Surgical Research Madrid, Spain October 2015. PMID- 26864559 TI - Association of oesophageal radiation dose volume metrics, neutropenia and acute radiation oesophagitis in patients receiving chemoradiotherapy for non-small cell lung cancer. AB - INTRODUCTION: The relationship between oesophageal radiation dose volume metrics and dysphagia in patients having chemoradiation (CRT) for non-small cell lung cancer (NSCLC) is well established. There is also some evidence that neutropenia is a factor contributing to the severity of oesophagitis. We retrospectively analysed acute radiation oesophagitis (ARO) rates and severity in patients with NSCLC who received concurrent chemotherapy and high dose radiation therapy (CRT). We investigated if there was an association between grade of ARO, neutropenia and radiation dose volume metrics. MATERIAL AND METHODS: Patients with NSCLC having concurrent CRT who had RT dose and toxicity data available were eligible. Exclusion criteria included previous thoracic RT, treatment interruptions and non standard dose regimens. RT dosimetrics included maximum and mean oesophageal dose, oesophagus dose volume and length data. RESULTS: Fifty four patients were eligible for analysis. 42 (78 %) patients received 60 Gy. Forty four (81 %) patients received carboplatin based chemotherapy. Forty eight (89 %) patients experienced ARO >= grade 1 (95 % CI: 78 % to 95 %). ARO grade was associated with mean dose (rs = 0.27, p = 0.049), V20 (rs = 0.31, p = 0.024) and whole oesophageal circumference receiving 20 Gy (rs = 0.32 p = 0.019). In patients who received these doses, V20 (n = 51, rs = 0.36, p = 0.011), V35 (n = 43, rs = 0.34, p = 0.027) and V60 (n = 25, rs = 0.59, P = 0.002) were associated with RO grade. Eleven of 25 (44 %) patients with ARO >= grade 2 also had >= grade 2 acute neutropenia compared with 5 of 29 (17 %) patients with RO grade 0 or 1 (p = 0.035). CONCLUSION: In addition to oesophageal dose-volume metrics, neutropenia may also be a risk factor for higher grades of ARO. PMID- 26864561 TI - Asymmetric Parachute-Like Tricuspid Valve with Severe Tricuspid Regurgitation in an Adult Patient. PMID- 26864554 TI - Phytochemicals for the Management of Melanoma. AB - Melanoma claims approximately 80% of skin cancer-related deaths. Its life threatening nature is primarily due to a propensity to metastasize. The prognosis for melanoma patients with distal metastasis is bleak, with median survival of six months even with the latest available treatments. The most commonly mutated oncogenes in melanoma are BRAF and NRAS accounting approximately 60% and 20% of cases, respectively. In malignant melanoma, accumulating evidence suggests that multiple signaling pathways are constitutively activated and play an important role in cell proliferation, cell survival, epithelial to mesenchymal transition, metastasis and resistance to therapeutic regimens. Phytochemicals are gaining considerable attention because of their low toxicity, low cost, and public acceptance as dietary supplements. Cell culture and animals studies have elucidated several cellular and molecular mechanisms by which phytochemicals act in the prevention and treatment of metastatic melanoma. Several promising phytochemicals, such as, fisetin, epigallocatechin-3-gallate, resveratrol, curcumin, proanthocyanidins, silymarin, apigenin, capsaicin, genistein, indole-3 carbinol, and luteolin are gaining considerable attention and found in a variety of fresh fruits, vegetables, roots, and herbs. In this review, we will discuss the preventive potential, therapeutic effects, bioavailability and structure activity relationship of these selected phytochemicals for the management of melanoma. PMID- 26864562 TI - Development and virucidal activity of a novel alcohol-based hand disinfectant supplemented with urea and citric acid. AB - BACKGROUND: Hand disinfectants are important for the prevention of virus transmission in the health care system and environment. The development of broad antiviral spectrum hand disinfectants with activity against enveloped and non enveloped viruses is limited due to a small number of permissible active ingredients able to inactivate viruses. METHODS: A new hand disinfectant was developed based upon 69.39 % w/w ethanol and 3.69 % w/w 2-propanol. Different amounts of citric acid and urea were added in order to create a virucidal claim against poliovirus (PV), adenovirus type 5 (AdV) and polyomavirus SV40 (SV40) as non-enveloped test viruses in the presence of fetal calf serum (FCS) as soil load. The exposure time was fixed to 60 s. RESULTS: With the addition of 2.0 % citric acid and 2.0 % urea an activity against the three test viruses was achieved demonstrating a four log10 reduction of viral titers. Furthermore, this formulation was able to inactivate PV, AdV, SV40 and murine norovirus (MNV) in quantitative suspension assays according to German and European Guidelines within 60 s creating a virucidal claim. For inactivation of vaccinia virus and bovine viral diarrhea virus 15 s exposure time were needed to demonstrate a 4 log10 reduction resulting in a claim against enveloped viruses. Additionally, it is the first hand disinfectant passing a carrier test with AdV and MNV. CONCLUSIONS: In conclusion, this new formulation with a low alcohol content, citric acid and urea is capable of inactivating all enveloped and non-enveloped viruses as indicated in current guidelines and thereby contributing as valuable addition to the hand disinfection portfolio. PMID- 26864563 TI - HPLC-DAD phenolic profile, cytotoxic and anti-kinetoplastidae activity of Melissa officinalis. AB - Context Melissa officinalis subsp. inodora Bornm. (Lamiaceae) has been used since ancient times in folk medicine against various diseases, but it has not been investigated against protozoa. Objective To evaluate the activities of M. officinalis against Leishmania braziliensis, Leishmania infantum and Trypanosoma cruzi as well as its cytotoxicity in fibroblast cell line. Materials and methods The fresh leaves were chopped into 1 cm(2) pieces, washed and macerated with 99.9% of ethanol for 72 h at room temperature. Antiparasitic activity of M. officinalis was accessed by direct counting of cells after serial dilution, while the cytotoxicity of M. officinalis was evaluated in fibroblast cell line (NCTC929) by measuring the reduction of resazurin. The test duration was 24 h. High-performance liquid chromatography (HPLC) was used to characterise the extract. Results The extract at concentrations of 250 and 125 MUg/mL inhibited 80.39 and 54.27% of promastigote (LC50 value = 105.78 MUg/mL) form of L. infantum, 80.59 and 68.61% of L. brasiliensis (LC50 value = 110.69 MUg/mL) and against epimastigote (LC50 value = 245.23 MUg/mL) forms of T. cruzi with an inhibition of 54.45 and 22.26%, respectively, was observed. The maximum toxicity was noted at 500 MUg/mL with 95.41% (LC50 value = 141.01 MUg/mL). The HPLC analysis identified caffeic acid and rutin as the major compounds. Discussion The inhibition of the parasites is considered clinically relevant (< 500 MUg/mL). Rutin and caffeic acids may be responsible for the antiprotozoal effect of the extract. Conclusion The ethanol extract of M. officinalis can be considered a potential alternative source of natural products with antileishmania and antitrypanosoma activities. PMID- 26864564 TI - Novel immunoassay and rapid immunoaffinity chromatography method for the detection and selective extraction of naringin in Citrus aurantium. AB - In this work, a novel monoclonal antibody specific for naringin was prepared and characterized. Subsequently, an indirect competitive enzyme-linked immunosorbent assay for naringin was developed, with an effective range from 4.8 to 156 ng/mL naringin. Next, an immunoaffinity column was obtained by coupling anti-naringin monoclonal antibodies to CNBr-activated Sepharose 4B and a rapid immunoaffinity chromatography assay for naringin was developed. The immunoaffinity column was used to separate naringin from Citrus aurantium. The results showed that 1 g of the dry Sepharose 4B can couple 10 mg of immunoglobulin G. And the immunoaffinity column can efficiently and specifically capture approximately 250 MUg of naringin without cross reacting with its structurally similar compounds. Moreover, our results indicate that the application of immunoaffinity chromatography can simplify the pretreatment and the isolation process greatly compared to conventional methods, providing a potential method for extracting the target component from structurally similar compounds in natural products. PMID- 26864566 TI - Longitudinal trends in global obesity research and collaboration: a review using bibliometric metadata. AB - The goal of this study was to understand research trends and collaboration patterns together with scholarly impact within the domain of global obesity research. We developed and analysed bibliographic affiliation data collected from 117,340 research articles indexed in Scopus database on the topic of obesity and published from 1993-2012. We found steady growth and an exponential increase of publication numbers. Research output in global obesity research roughly doubled each 5 years, with almost 80% of the publications and authors from the second decade (2003-2012). The highest publication output was from the USA - 42% of publications had at least one author from the USA. Many US institutions also ranked highly in terms of research output and collaboration. Fifteen of the top 20 institutions in terms of publication output were from the USA; however, several European and Japanese research institutions ranked more highly in terms of average citations per paper. The majority of obesity research and collaboration has been confined to developed countries although developing countries have showed higher growth in recent times, e.g. the publication ratio between 2003-2012 and 1993-2002 for developing regions was much higher than that of developed regions (9:1 vs. 4:1). We also identified around 42 broad disciplines from authors' affiliation data, and these showed strong collaboration between them. Overall, this study provides one of the most comprehensive longitudinal bibliometric analyses of obesity research. This should help in understanding research trends, spatial density, collaboration patterns and the complex multi-disciplinary nature of research in the obesity domain. PMID- 26864565 TI - Equity in children's dental caries before and after cessation of community water fluoridation: differential impact by dental insurance status and geographic material deprivation. AB - BACKGROUND: One of the main arguments made in favor of community water fluoridation is that it is equitable in its impact on dental caries (i.e., helps to offset inequities in dental caries). Although an equitable effect of fluoridation has been demonstrated in cross-sectional studies, it has not been studied in the context of cessation of community water fluoridation (CWF). The objective of this study was to compare the socio-economic patterns of children's dental caries (tooth decay) in Calgary, Canada, in 2009/10 when CWF was in place, and in 2013/14, after it had been discontinued. METHODS: We analyzed data from population-based samples of schoolchildren (grade 2) in 2009/10 and 2013/14. Data on dental caries (decayed, missing, and filled primary and permanent teeth) were gathered via open mouth exams conducted in schools by registered dental hygienists. We examined the association between dental caries and 1) presence/absence of dental insurance and 2) small area index of material deprivation, using Poisson (zero-inflated) and logistic regression, for both time points separately. For small-area material deprivation at each time point, we also computed the concentration index of inequality for each outcome variable. RESULTS: Statistically significant inequities by dental insurance status and by small area material deprivation were more apparent in 2013/14 than in 2009/10. CONCLUSIONS: Results are consistent with increasing inequities in dental caries following cessation of CWF. However, further research is needed to 1) confirm the effects in a study that includes a comparison community, and 2) explore possible alternative reasons for the findings, including changes in treatment and preventive programming. PMID- 26864568 TI - Extension of recovery time from fatigue by repeated rest with short-term sleep during continuous fatigue load: Development of chronic fatigue model. AB - Homeostasis is known to be involved in maintaining the optimal internal environment, helping to achieve the best performance of biological functions. At the same time, a deviation from optimal conditions often attenuates the performance of biological functions, and such restricted performance could be considered as individual fatigue, including physical and mental fatigue. The present study seeks to develop an animal model of chronic or subacute fatigue in which the recovery time is extended through the gradual disruption of homeostasis. We show that repeated short-term rest periods with certain lengths of sleep during continuous fatigue loading extend recovery from spontaneous nighttime activity but not physical performance in comparison with a continuous fatigue-loading procedure. Furthermore, the immobility time in a forced swimming test was extended by repeated short-term rests. These results suggest that repeated short-term rest with certain lengths of sleep during continuous fatigue loading is able to extend the recovery from mental fatigue but not from physical fatigue and that this effect might occur via the disruption of a homeostatic mechanism that is involved in restoring the optimal internal environment. PMID- 26864567 TI - Mitochondrial Dynamics Tracking with Two-Photon Phosphorescent Terpyridyl Iridium(III) Complexes. AB - Mitochondrial dynamics, including fission and fusion, control the morphology and function of mitochondria, and disruption of mitochondrial dynamics leads to Parkinson's disease, Alzheimer's disease, metabolic diseases, and cancers. Currently, many types of commercial mitochondria probes are available, but high excitation energy and low photo-stability render them unsuitable for tracking mitochondrial dynamics in living cells. Therefore, mitochondrial targeting agents that exhibit superior anti-photo-bleaching ability, deep tissue penetration and intrinsically high three-dimensional resolutions are urgently needed. Two-photon excited compounds that use low-energy near-infrared excitation lasers have emerged as non-invasive tools for cell imaging. In this work, terpyridyl cyclometalated Ir(III) complexes (Ir1-Ir3) are demonstrated as one- and two photon phosphorescent probes for real-time imaging and tracking of mitochondrial morphology changes in living cells. PMID- 26864569 TI - In response to Immunohistochemical localization of OCT2 in the cochlea of various species. PMID- 26864570 TI - PTSD REMISSION AFTER PROLONGED EXPOSURE TREATMENT IS ASSOCIATED WITH ANTERIOR CINGULATE CORTEX THINNING AND VOLUME REDUCTION. AB - BACKGROUND: Brain structures underlying posttraumatic stress disorder (PTSD) have been a focus of imaging studies, but associations between treatment outcome and alterations in brain structures remain largely unexamined. We longitudinally examined the relation of structural changes in the rostral anterior cingulate cortex (rACC), a previously identified key region in the PTSD fear network, to outcome of prolonged exposure (PE) treatment. METHOD: The sample included 78 adults (53 women): 41 patients with PTSD and 37 trauma-exposed healthy volunteers (TE-HCs). Patients underwent a 10-week course of PE treatment and completed pre- and posttreatment assessments and magnetic resonance imaging (MRI) structural scans. TE-HCs also underwent assessment and MRI at baseline and 10 weeks later. PE remitters (n = 11), nonremitters (n = 14), and TE-HCs, were compared at baseline on demographic and clinical characteristics and ACC structure. Remitters, nonremitters, and TE-HCs were compared for pre- to posttreatment clinical and structural ACC change, controlling for potential confounding variables. RESULTS: There were no baseline differences in structure between PTSD and TE-HCs or remitters and nonremitters. Following treatment, PTSD remitters exhibited cortical thinning and volume decrease in the left rACC compared with PTSD nonremitters and TE-HCs. CONCLUSIONS: These results, while in need of replication, suggest that PE treatment for PTSD, by extinguishing maladaptive trauma associations, may promote synaptic plasticity and structure change in rACC. Future research should explore possible underlying mechanisms. PMID- 26864571 TI - Corticosteroids in treatment of aspiration-related acute respiratory distress syndrome: results of a retrospective cohort study. AB - BACKGROUND: Acute stroke patients suffering from aspiration may present with acute respiratory distress syndrome (ARDS). There is still a lack of convincing data about the efficacy of corticosteroids in the treatment of aspiration-related ARDS. Therefore, we evaluated the clinical impact of corticosteroids on aspiration-related ARDS. METHODS: Between 2012 and 2014, we conducted a retrospective study among acute stroke patients diagnosed with aspiration-related ARDS. The data analyzed included demographic characteristics, clinical manifestations, laboratory examinations, chest imaging, and hospital discharge status. RESULTS: Seventy-three acute stroke patients were diagnosed with aspiration-related ARDS. The hospital mortality rate was 39.7%. Corticosteroids were administered in 47 patients (64.4%). The mean dosage was 1.14 (standard deviation [SD] 0.47) mg/kg daily of methylprednisolone (or an equivalent) by intravenous infusion for a period of 7.3 (SD 3.8) days. Ground glass opacities in chest computed tomography images were resolved when corticosteroids were administered. The admission National Institute of Health Stroke Scale score (odds ratio [OR] 5.17, 95% confidence interval [CI] 1.27-10.64) and Acute Physiology and Chronic Health Evaluation II score (OR 2.00, 95% CI 1.12-3.56) were associated with an increased risk of hospital mortality, while albumin (OR 0.81, 95% CI 0.64-0.92) and corticosteroids therapy (OR 0.50, 95% CI 0.35-0.70) were associated with a decreased risk. CONCLUSIONS: Low-dose and short-term corticosteroid therapy may have an impact on survival in aspiration-related ARDS. The presence of ground glass opacities on the chest computed tomography, performed to rule out aspiration-related ARDS, could be translated into an increased possibility of positive response to corticosteroid therapy. PMID- 26864572 TI - Higher nurse to patient ratio is linked to reduced risk of inpatient death. PMID- 26864574 TI - When the face says it all: dysmorphology in identifying syndromic causes of epilepsy. AB - Identifying the underlying cause of epilepsy often helps in choosing the appropriate management, suggests the long-term prognosis and clarifies the risk of the same condition in relatives. Epilepsy has many causes and a small but significant proportion of affected people have an identifiable genetic cause. Here, we discuss the role of genetic testing in adults with epilepsy, focusing on dysmorphic features noticeable on physical examination that might provide a strong clue to a specific genetic syndrome. We give illustrative examples of recognisable facial 'gestalt'. An astute clinician can recognise such clues and significantly shorten the process of making the underlying diagnosis in their patient. PMID- 26864575 TI - Ramsay Hunt syndrome. PMID- 26864573 TI - Intraperitoneally infused human mesenchymal stem cells form aggregates with mouse immune cells and attach to peritoneal organs. AB - BACKGROUND: Mesenchymal stem/progenitor cells (MSC) have shown beneficial effects in many models of disease in part by modulating excessive inflammatory and immune responses. Frequently the beneficial effects of MSC persist long after their disappearance from host tissues, suggesting that MSC interact with intermediate cells in the host that relay or amplify their effects. The cells have usually been injected intravenously, but beneficial effects have also been reported with intraperitoneal (IP) injection of MSC. However the fate of IP injection of MSC has not been examined. METHODS: The fate of the human MSC injected IP into immune competent mice was studied. In vivo imaging was used to track green fluorescent protein-labeled MSC in the peritoneal cavity. In addition, their retention in peritoneal tissues was measured by real-time polymerase chain reaction for human GAPDH mRNA. To describe the effects of human MSC on the immune system of the peritoneum, the peritoneal lavage, omentum, lymph nodes and mesenteric tissues were collected. Flow cytometry was used to evaluate the immune cell populations, while cytokine/chemokine production was measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Challenge with lipopolysaccharide at 3 days after the administration of MSC was used to evaluate the preconditioning of the immune system. RESULTS: Within 20 min, single MSC were no longer detected in peritoneal lavage fluid. Instead they were recovered as aggregates of varying size that contained mouse macrophages and a few B220+ lymphocytes. After 1 day, most of the aggregates containing live MSC were attached to sites throughout the peritoneal cavity including the omentum and mesentery. Less than 0.05 % of the live injected cells were detected in the spleen and jejunal lymph nodes. In all locations, MSC colocalized with mouse macrophages and B220+ lymphocytes. Attachment to the omentum and mesentery was accompanied by the recruitment of immune cells and changes in the production of a series of mouse cytokines. A similar increase in mouse cytokines in the peritoneum was seen after IP injections of human fibroblasts. CONCLUSIONS: IP injected human MSC rapidly formed aggregates with mouse macrophages and B220+ lymphocytes and attached to the walls of the peritoneal cavity. The formation of the aggregates probably limits access of the cells to the systemic circulation. PMID- 26864576 TI - The significance and the necessity of routinely performing lung ultrasound in the neonatal intensive care units. AB - Various lung diseases are the most common conditions and the leading cause of hospital admission and death in newborns. Historically, the diagnosis and differential diagnosis of lung diseases primarily relied on conventional chest X ray and computed tomography (CT) scans, however, chest X-ray and CT scans suffer from obvious limitations, while lung ultrasound has many kinds of advantages for the diagnosis and differential diagnosis of lung diseases. The significance and the necessity of lung ultrasound in the diagnosis of neonatal lung diseases will be introduced in this paper. PMID- 26864577 TI - Implicit learning deficits among adults with developmental dyslexia. AB - The aim of the present study was to investigate implicit learning processes among adults with developmental dyslexia (DD) using a visual linguistic artificial grammar learning (AGL) task. Specifically, it was designed to explore whether the intact learning reported in previous studies would also occur under conditions including minimal training and instructions that do not reveal the grammatical nature of the strings. Twenty-nine (14 DD and 15 typical development (TD)) adults were presented with letter sequences in the training phase and were asked to classify the test strings for their grammaticality. The results of the d' measures in the implicit task indicated that learning had occurred for both groups, as the proportion of hits exceeded the proportion of false alarms. However, a significant difference was found between the groups in their learning measures, as TD readers performed significantly better than individuals with DD, supporting the assumption of a deficit in implicit sequential learning processes among individuals with DD. In order to examine whether the deficit found in the first experiment was indeed due to a deficit in implicit processes, a second experiment was designed in which explicit instructions were given during an AGL task. Results of the explicit task strengthen the assumption that the deficit is indeed specific to implicit sequential processes, as no difference between the groups was found when participants were aware of the existence of the grammar underlying the strings. Theoretical and clinical implications are discussed. PMID- 26864578 TI - Correction. PMID- 26864579 TI - Development of skills-based competencies for forensic nurse examiners providing elder abuse care. AB - OBJECTIVE: As a critical step in advancing a comprehensive response to elder abuse built on existing forensic nursing-led hospital-based programmes, we developed a list of skills-based competencies for use in an Elder Abuse Nurse Examiner curriculum. PARTICIPANTS AND SETTING: Programme leaders of 30 hospital based forensic nursing-led sexual assault and domestic violence treatment centres. PRIMARY AND SECONDARY OUTCOME MEASURES: 149 verbatim recommendations for components of an elder abuse response were identified from a systematic scoping review. In 2 online Delphi consensus survey rounds, these components of care were evaluated by an expert panel for their overall importance to the elder abuse intervention under development and for their appropriateness to the scope of practice of an elder abuse nurse examiner. The components retained after evaluation were translated into skills-based competencies using Bloom's Taxonomy of Learning and, using the Nominal Group Technique, were subsequently reviewed and revised by a subset of members of the expert panel in a consensus meeting. RESULTS: Of the 148 recommendations evaluated, 119 were rated as important and achieved consensus or high level of agreement. Of these, 101 were determined to be within the scope of practice of an Elder Abuse Nurse Examiner and were translated into skills-based competencies. Following review and revision by meeting experts, 47 final competencies were organised by content into 5 metacompetencies: documentation, legal and legislative issues; interview with older adult, caregiver and other relevant contacts; assessment; medical and forensic examination; and case summary, discharge plan and follow-up care. CONCLUSIONS: We determined the skills-based competencies of importance to training forensic nurse examiners to respond to elder abuse in the context of a hospital-based intervention. These findings may have implications for violence and abuse treatment programmes with a forensic nursing component that are considering the provision of a dedicated response to the abuse of older women and men. PMID- 26864581 TI - PPARdelta agonist GW0742 ameliorates Abeta1-42-induced hippocampal neurotoxicity in mice. AB - Amyloid-beta deposition is thought to be associated with memory deficits, neuroinflammation, apoptotic responses, and progressive neuronal death manifested in Alzheimer's disease. Peroxisome proliferator-activated receptor delta (PPARdelta) is a transcription factor with potent anti-inflammatory effect. In the current study, the effect of GW0742, a selective PPARdelta agonist, on Abeta1 42-induced neurotoxicity was investigated in the hippocampus of mice. Intra hippocampal infusion of aggregated Abeta1-42 oligomer (410pmol/mouse) remarkably damaged learning and memory in the Morris water maze (MWM) and Y-maze tests, accompanied by decreased expression of PPARdelta in the hippocampus as confirmed by Western blot. Intra-hippocampal infusion of GW0742 (1.06 mM/mouse) significantly improved Abeta1-42-induced memory deficits in mice, reversed Abeta1 42-induced hippocampal PPARdelta down-regulation and repressed Abeta1-42 triggered neuroinflammatory and apoptotic responses, indicated by decreased nuclear NF-kappaB p65, TNF-alpha, IL-1beta as well as a decrease in cleaved caspase-3 and increased ratio of Bcl-2/Bax in the hippocampus. These results suggest that PPARdelta activation ameliorates Abeta1-42-induced hippocampal neurotoxicity, and it might play a crucial role in Alzheimer's disease. PMID- 26864580 TI - The Human Microbiome during Bacterial Vaginosis. AB - Bacterial vaginosis (BV) is the most commonly reported microbiological syndrome among women of childbearing age. BV is characterized by a shift in the vaginal flora from the dominant Lactobacillus to a polymicrobial flora. BV has been associated with a wide array of health issues, including preterm births, pelvic inflammatory disease, increased susceptibility to HIV infection, and other chronic health problems. A number of potential microbial pathogens, singly and in combinations, have been implicated in the disease process. The list of possible agents continues to expand and includes members of a number of genera, including Gardnerella, Atopobium, Prevotella, Peptostreptococcus, Mobiluncus, Sneathia, Leptotrichia, Mycoplasma, and BV-associated bacterium 1 (BVAB1) to BVAB3. Efforts to characterize BV using epidemiological, microscopic, microbiological culture, and sequenced-based methods have all failed to reveal an etiology that can be consistently documented in all women with BV. A careful analysis of the available data suggests that what we term BV is, in fact, a set of common clinical signs and symptoms that can be provoked by a plethora of bacterial species with proinflammatory characteristics, coupled to an immune response driven by variability in host immune function. PMID- 26864584 TI - A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management. AB - This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study. PMID- 26864583 TI - Cardiac Protective Effects of Moringa oleifera Seeds in Spontaneous Hypertensive Rats. AB - BACKGROUND: Hypertension is characterized by a maintained high blood pressure leading to cardiac complications such as left ventricular hypertrophy and fibrosis and an increased risk of heart failure and myocardial infarction. This study investigated the cardiac effects of oral administration of Moringa oleifera (MOI) seed powder in spontaneous hypertensive rats (SHR). METHODS: SHR received food containing MOI seed powder (750mg/d, 8 weeks) or normal food. In vivo measurement of hemodynamic parameters by telemetry and cardiac structure and function analysis by echocardiography were performed. Histological studies were performed to determine fibrosis and protein expression. RESULTS: MOI treatment did not modify blood pressure in SHR but reduced nocturnal heart rate and improved cardiac diastolic function (reduction of isovolumetric relaxation time and deceleration time of the E wave, increase of ejection volume and cardiac output compared to nontreated SHR). Left ventricular anterior wall thickness, interseptal thickness on diastole, and relative wall thickness were reduced after MOI treatment. Furthermore, we found a significant reduction of fibrosis in the left ventricle of MOI-treated SHR. This antihypertrophic and antifibrotic effect of MOI was associated with increased expression of peroxisome proliferator activated receptor (PPAR)-alpha and delta, reduced cardiac triglyceride level, and enhanced plasmatic prostacyclins. CONCLUSIONS: Our data show a beneficial effect of MOI on the cardiac structure and function in SHR associated with an upregulation of PPAR-alpha and delta signaling. This study thus provides scientific rational support for the empirical use of MOI in the traditional Malagasy medicine against cardiac diseases associated with blood pressure overload. PMID- 26864582 TI - Increase of kisspeptin-positive cells in the hypothalamus of a rat model of polycystic ovary syndrome. AB - Kisspeptin, a hypothalamic neuropeptide, is expressed in the arcuate nucleus (ARC) that is considered as the center of the gonadotropin-releasing hormone (GnRH)-pulse generator. We hypothesized that kisspeptin expressed in the ARC is implicated in the disturbance of the hypothalamus-pituitary-ovary axis observed in polycystic ovary syndrome (PCOS). To test this hypothesis, we evaluated the hormonal profiles, luteinizing hormone (LH) pulse, and ARC kisspeptin immunoreactivity in a PCOS rat model using the anti-progestin RU486. We found an alteration of the LH pulse, including a trend towards an increased mean LH concentration and area under the curve, and a significant upregulation of the mean LH pulse amplitude. Additionally, a higher number of kisspeptin-positive cells was observed in the ARC of RU486-treated rats than in the ARC of intact rats. These results suggest the possible involvement of hypothalamic kisspeptin in the hypothalamus-pituitary-ovary axis and therefore, in PCOS pathophysiology. PMID- 26864585 TI - Endoscopic management of a gastric leak after laparoscopic sleeve gastrectomy using the over-the-scope-clip (Ovesco(r)) system. AB - Laparoscopic sleeve gastrectomy is currently used for the management of morbid obesity. Gastric fistula is the primary life-threatening complication, and its resolution continues to be a strong challenge for surgeons. Multiple treatment options are available, ranging from conservative therapy to endoscopic use of clips or stents, and even surgical reoperation involving total gastrectomy or conversion to a different bariatric technique. The applicability of each individual option will depend on the type of fistula and the patient clinical status. A clinical case is reported of a 29-year-old male patient with a body mass index at 49% who following laparoscopic sleeve gastrectomy had a delayed gastric fistula that failed to respond to conservative management but was successfully treated using the over-the-scope clip (Ovesco(r)) system. PMID- 26864586 TI - [Chronic low back pain : Comparison of mobilization and core stability exercises]. AB - BACKGROUND: For the treatment of chronic low back pain (cLBP), both core stability and mobilization exercises were introduced. The aim of this prospective randomized clinical pilot study was to compare the efficacy of mobilization and core stability exercises with regard to objective and subjective outcome measures in patients with cLBP. METHOD: After a per-protocol analysis, the data of 27 patients with cLBP, who were randomly allocated to one of the two groups, were analyzed. The intervention group (GM) performed mobilization exercises using the BALLance-Methode(r), the control group (GS) carried out core stability exercises for 4 weeks, and continued the exercises for an additional 4 weeks at home. Flexibility, strength endurance of the core stabilizing muscles, pain-induced disability, and pain avoidance behavior were the objective and subjective outcomes that were measured before, 4 weeks after, and 8 weeks after the onset of the intervention. The significance of differences within and between groups was analyzed. RESULTS: During the observation period, only in the GS patients could maintain the prone-plank position and the side-plank position improvements over time (p < 0.001), with significant differences compared with the GM (p < 0.05). Within both groups significant improvements in the subjective outcome measures were found (p < 0.05). Therefore, no significant differences existed between the groups. CONCLUSION: With regard to their daily complaints, patients with cLBP can be treated using standardized mobilization exercises in addition to core stability exercises. PMID- 26864587 TI - Quantifying population declines based on presence-only records for red-list assessments. AB - Accurate trend estimates are necessary for understanding which species are declining and which are most in need of conservation action. Imperfect species detection may result in unreliable trend estimates because this may lead to the overestimation of declines. Because many management decisions are based on population trend estimates, such biases could have severe consequences for conservation policy. We used an occupancy-modeling framework to estimate detectability and calculate nationwide population trends for 14 Swiss amphibian species both accounting for and ignoring imperfect detection. Through the application of International Union for Conservation of Nature Red List criteria to the different trend estimates, we assessed whether ignoring imperfect detection could affect conservation policy. Imperfect detection occurred for all species and detection varied substantially among species, which led to the overestimation of population declines when detectability was ignored. Consequently, accounting for imperfect detection lowered the red-list risk category for 5 of the 14 species assessed. We demonstrate that failing to consider species detectability can have serious consequences for species management and that occupancy modeling provides a flexible framework to account for observation bias and improve assessments of conservation status. A problem inherent to most historical records is that they contain presence-only data from which only relative declines can be estimated. A move toward the routine recording of nonobservation and absence data is essential if conservation practitioners are to move beyond this toward accurate population trend estimation. PMID- 26864591 TI - Editorial Comment for Yuan et al. PMID- 26864590 TI - DeltaNp63alpha attenuates tumor aggressiveness by suppressing miR-205/ZEB1 mediated epithelial-mesenchymal transition in cervical squamous cell carcinoma. AB - Cervical cancer is one of the most common female cancers worldwide. Although the therapeutic outcomes of patients with early-stage cervical cancer have been significantly improved in the past decades, tumor metastasis and recurrence remain the major causes of cervical cancer-related deaths. In cervical squamous cell carcinoma (SCC), the aberrant activation of epithelial-mesenchymal transition (EMT), a crucial process in invasion and metastasis of epithelial cancer, could promote lymph nodal metastasis and recurrence, and predicts poor prognosis. In this study, we show that the expression levels of EMT markers, beta catenin and Vimentin, are associated with the p63 isoform DeltaNp63alpha in SCC by using immunohistochemistry staining and analysis. Compared to the control SiHa cells (SiHa-NC), the expression of E-cadherin and beta-catenin are upregulated, while Vimentin and ZEB1 are downregulated in the constructed SiHa cell line with stable DeltaNp63alpha overexpression (SiHa-DeltaNp63alpha). Besides, the migration and invasion abilities are also suppressed in SiHa-DeltaNp63alpha cells with a typical epithelial morphology with cobblestone-like shape, suggesting that DeltaNp63alpha is a vital EMT repressor in SCC cells. In addition, the involvement of miR-205/ZEB1 axis in the inhibition effect of DeltaNp63alpha on EMT program is revealed by a miRNA array and confirmed by the subsequent transfection of the miR-205 mimic and antagomir. Moreover, SCC patients with low DeltaNp63alpha expression and high EMT level show more frequent metastasis and recurrence as well as reduced overall survival. Therefore, EMT program and its vital repressor DeltaNp63alpha could be used as biomarkers for tumor metastasis and recurrence in cervical cancer. PMID- 26864592 TI - Vismodegib and Physeal Closure in a Pediatric Patient. PMID- 26864589 TI - Cancer stem cells, metabolism, and therapeutic significance. AB - Cancer stem cells (CSCs) have attracted much attention of the research community in the recent years. Due to their highly tumorigenic and drug-resistant properties, CSCs represent important targets for developing novel anticancer agents and therapeutic strategies. CSCs were first described in hematopoietic malignancies and subsequently identified in various types of solid tumors including brain, breast, lung, colon, melanoma, and ovarian cancer. CSCs possess special biological properties including long-term self-renewal capacity, multi lineage differentiation, and resistance to conventional chemotherapy and radiotherapy. As such, CSCs are considered as a major source of residual disease after therapy leading to disease occurrence. Thus, it is very important to understand the cellular survival mechanisms specific to CSCs and accordingly develop effective therapeutic approaches to eliminate this subpopulation of cancer cells in order to improve the treatment outcome of cancer patients. Possible therapeutic strategies against CSCs include targeting the self-renewal pathways of CSCs, interrupting the interaction between CSCs and their microenvironment, and exploiting the unique metabolic properties of CSCs. In this review article, we will provide an overview of the biological characteristics of CSCs, with a particular focus on their metabolic properties and potential therapeutic strategies to eliminate CSCs. PMID- 26864593 TI - Dynamical Dimension to the Hofmeister Series: Insights from First-Principles Simulations. AB - A systematic characterization of the competing kosmotropic and chaotropic effects of a series of divalent salts on the aqueous H-bonding structure by means of first-principles molecular dynamics simulations is presented. The structural properties are quantified by means of experimental and computed (1) H NMR chemical shifts, whereby the local environments of cations and anions can be discriminated. Complementary to the well-established structural features, a dynamical aspect is added to the concept of kosmotropes and chaotropes. The H bond dynamics, quantified in terms of the H-bonding autocorrelation functions, shows a good correlation with the structural kosmotropic and chaotropic modifications, which are commonly referred to as the Hofmeister series. The considerably enhanced (reduced) fluctuations of the H-bonding network in the hydration shells around the anions (cations) are a complementary dynamical dimension to the concept of kosmotropic/chaotropic behavior of solvated ions. PMID- 26864595 TI - Offline: Health--the Chinese dream. PMID- 26864594 TI - The use of brief post-surgical low frequency electrical stimulation to enhance nerve regeneration in clinical practice. AB - Despite efforts to enhance peripheral nerve regeneration, there has been little progress in improving clinical outcomes. Recently, a method of brief post surgical low frequency electrical stimulation of surgically repaired nerves has been developed. It was shown to accelerate axon outgrowth across the repair site and it hastened target reinnervation. In this brief review, we describe the mechanistic insights and functional impacts of the post-surgical electrical stimulation that have been gained through animal studies. Brain-derived neurotrophic factor, cyclic AMP and regeneration-associated genes play a vital role in expediting the outgrowth of axons across the injury site. The method of stimulation has also been shown to be effective in patients with severe compressive neuropathy as well as those with digital nerve laceration. Its clinical feasibility and positive impact open the door of further clinical translation in other peripheral nerve injuries. PMID- 26864596 TI - Triggering the approach of an arene or heteroarene towards an aldehyde via Lewis acid-aldehyde communication. AB - The present work reports a combined experimental/computational study of the Lewis acid promoted hydroxyalkylation reaction involving aldehyde and arene/heteroarene and reveals a mechanism in which the rate determining aldehyde to alcohol formation via a four-member cyclic transition state (TS) involves a transfer of hydrogen from arene/heteroarene C-H to aldehyde oxygen with the breaking of the C H bond and formation of C-C and O-H bonds. The effect of different Sn(iv) derivatives on the hydroxyalkylation reaction from different in situ NMR and computational studies reveals that although the exergonic formation of the intermediate and its gained electrophilicity at the carbonyl carbon drive the reaction in SnCl4 compared to other Sn(iv) derivatives, the overall reaction is low yielding because of its stable intermediate. With respect to different aldehydes, LA promoted hydroxylation was found to be more feasible for an electron withdrawing aldehyde compared to electron rich aldehyde because of lower stability, enhanced electrophilicity gained at the aldehyde center, and a lower activation barrier between its intermediate and TS in the former as compared to the latter. The relative stability of the LA-aldehyde adduct decreases in the order SnCl4 > AlCl3 > InCl3 > BF3 > ZnCl2 > TiCl4 > SiCl4, while the activation barrier (DeltaG(#)) between intermediate and transition states increases in the order AlCl3 < SnCl4 < InCl3 < BF3 < TiCl4 < ZnCl2 < SiCl4. On the other hand, the activation barriers in the case of different arenes/heteroarenes are in the order of indole < furan < anisole < thiophene < toluene < benzene < chlorobenzene < cyanobenzene, which suggests a facile reaction in the case of indole and the most difficult reaction in the case of cyanobenzene. The ease of formation of the corresponding diaryl methyl carbocation from the alcohol-LA intermediate is responsible for the determination of the undesired product and is found to be more viable in the case of strong LAs like AlCl3, InCl3 and SnCl4 because they have negative free energy of formation (DeltaG) for alcohol to the corresponding diaryl methyl carbocation. PMID- 26864598 TI - Two novel TSHR gene mutations (p.R528C and c.392+4del4) associated with congenital hypothyroidism. AB - Inactivating mutations of the thyrotropin receptor (TSHR) gene are responsible for non-goitrogenic congenital hypothyroidism (CHNG). This study aimed to investigate mutations in the TSHR gene in 20 children with CHNG. Genomic DNA was extracted from peripheral blood leukocytes and was used for mutation screening by direct sequencing. Analyses of the TSHR gene revealed two novel variants in a 2 year-old boy with thyroid hypoplasia: a missense mutation c.1582C>T (p.R528C) and a splice-site deletion c.392+4del4. Bioinformatics analysis demonstrated that both variants are capable of causing disease. Family members of the patient with two mutations and normal controls were also recruited and investigated. Germline mutations from the proband's family were consistent with an autosomal recessive inheritance pattern. These findings indicate that two novel inactivating mutations (p.R528C and c.392+4del4) in the TSHR gene can cause CHNG. PMID- 26864597 TI - Activity Variation of Phanerochaete chrysosporium under Nanosilver Exposure by Controlling of Different Sulfide Sources. AB - Due to the particular activation and inhibition behavior of silver nanoparticles (AgNPs) on microbes at various concentrations, it's crucial to exploit the special concentration effect in environment. Here, we studied the viability variation of Phanerochaete chrysosporium (P. chrysosporium) under exposure to citrate-coated AgNPs (Citrate-AgNPs) in the presence of different sulfide sources (an inorganic sulfide, NaHS and an organic sulfide, thioacetamide (TAA)). The results indicated that both NaHS and TAA can promote activation of P. chrysosporium by Citrate-AgNPs at a higher concentration, which was initial at toxic level. Treatment with various concentrations of Citrate-AgNPs (0-9 mg/L) demonstrated a maximum activation concentration (MAC) at 3 mg/L. With the increase in sulfide concentration, MAC transferred to higher concentration significantly, indicating the obvious "toxicity to activation" transformation at a higher concentration. Ag(+) testing exhibited that variations in sulfide induced Ag(+) concentration (3-7 MUg/L Ag(+)) accounted for the "toxicity to activation" transformation. In addition, the similar results were observed on antibacterial application using Escherichia coli as the model species. Based on the research results, the application of this transformation in improving antibacterial activity was proposed. Therefore, the antibacterial activity of AgNPs can be controlled, even at concentration, via adjusting for the sulfide concentration. PMID- 26864601 TI - Periodontal Conditions of Abutments and Non-Abutments in Removable Partial Dentures over 7 Years of Use. AB - PURPOSE: To evaluate the periodontal conditions and integrity of abutment and non abutment teeth of patients evaluated 7 years after insertion of the removable partial denture (RPD). MATERIALS AND METHODS: Twenty-two patients (17 women, 5 men) were assessed at the moment of denture insertion and 7 years later. The following items were verified in each assessment: bleeding on probing (BP), probing depth (PD), gingival recession (GR), and mobility (M), comparing direct and indirect abutment teeth, and the teeth not involved in the denture design. Tooth integrity was also evaluated and classified as intact when no caries or fractures were observed. The Kruskal-Wallis test was used to reveal statistical significance between the groups (p = 0.05) as well as the Bonferrroni-corrected Mann-Whitney test for post hoc comparison. The Wilcoxon test was used for evaluation within the group over time. Fisher's exact test was applied to cross data about abutment integrity. RESULTS: Statistically significant differences were found for GR (baseline, p < 0.001; 7 years, p < 0.001) and PD (baseline, p = 0.001; 7 years = 0.004) between the three groups at baseline and after 7 years of follow-up. Mean BP and M values increased from initial assessment to after 7 years of RPD use in every group, but no statistically significant difference was found between the groups. For abutment integrity, a statistically significant difference (p = 0.028) was observed, and the direct abutment exhibited more (33.3%) caries and fractures. CONCLUSION: RPDs generated more periodontal damage to direct abutments, since higher gingival recession probing depth indexes, and presence of caries and fractures were observed in comparison to indirect abutments and non-abutments. PMID- 26864599 TI - Tackling amyloidogenesis in Alzheimer's disease with A2V variants of Amyloid beta. AB - We developed a novel therapeutic strategy for Alzheimer's disease (AD) exploiting the properties of a natural variant of Amyloid-beta (Abeta) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Abeta, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Abeta1 6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Abeta1 6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Abeta toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Abeta1-6A2VTAT(D) inhibits Abeta aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AbetaA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Abeta1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Abeta production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics. PMID- 26864603 TI - Brain atrophy in Pelizaeus-Merzbacher disease. PMID- 26864604 TI - Ammonium-crown ether supramolecular cation-templated assembly of an unprecedented heterobicluster-metal coordination polymer with enhanced NLO properties. AB - An ammonium-crown ether host-guest supramolecular cation-templated synthetic methodology has been developed to construct a structurally unprecedented heterobicluster-metal coordination polymer (HCM-CP 1) based on tetranuclear clusters [WS4Cu3](+) with different connection environments, pentanuclear clusters [WS4Cu4](2+), and Cu(+) building metal ions. HCM-CP 1 exhibits enhanced NLO properties, which may be ascribed to the incorporation of diverse building cluster components. PMID- 26864602 TI - Synergistic infection of two viruses MCMV and SCMV increases the accumulations of both MCMV and MCMV-derived siRNAs in maize. AB - The co-infection of Maize chlorotic mottle virus (MCMV) and Sugarcane mosaic virus (SCMV) can cause maize lethal necrosis. However, the mechanism underlying the synergistic interaction between these two viruses remains elusive. In this study, we found that the co-infection of MCMV and SCMV increased the accumulation of MCMV. Moreover, the profiles of virus-derived siRNAs (vsiRNAs) from MCMV and SCMV in single- and co-infected maize plants were obtained by high-throughput sequencing. Our data showed that synergistic infection of MCMV and SCMV increased remarkably the accumulation of vsiRNAs from MCMV, which were mainly 22 and 21 nucleotides in length. The single-nucleotide resolution maps of vsiRNAs revealed that vsiRNAs were almost continuously but heterogeneously distributed throughout MCMV and SCMV genomic RNAs, respectively. Moreover, we predicted and annotated dozens of host transcript genes targeted by vsiRNAs. Our results also showed that maize DCLs and several AGOs RNAs were differentially accumulated in maize plants with different treatments (mock, single or double inoculations), which were associated with the accumulation of vsiRNAs. Our findings suggested possible roles of vsiRNAs in the synergistic interaction of MCMV and SCMV in maize plants. PMID- 26864605 TI - A review of estuarine fish research in South America: what has been achieved and what is the future for sustainability and conservation? AB - Estuarine fish research in South America began in the early 20th Century, but it is only within the last 40 years that detailed studies have been undertaken. This review firstly summarizes research results from South American estuaries by geographic area, starting with the temperate south-east, then the temperate-sub tropical transition zone in Brazil, then the semi-arid and tropical estuaries of north and north-east Brazil including the Amazon complex, then the north and Caribbean coasts and finally down the Pacific coast of the continent. They include almost all types of estuarine systems, from large open systems (e.g. the temperate Rio de La Plata and tropical Amazon) to extensive coastal lakes (e.g. the temperate Patos Lagoon and tropical Cienega Grande de Santa Marta). They encompass a broad range of climatic and vegetation types, from saltmarsh systems in the south-east and fjords in the south-west to both arid and humid tropical systems, dominated by mangroves in the north. Their tidal regimes range from microtidal (e.g. Mar Chiquita, Argentina) through mesotidal (e.g. Goiana, Brazil) to macrotidal in the Amazon complex where they can exceed 7 m. The review uses where possible the recent standardization of estuarine fish categories and guilds, but the ways that fishes use tropical South American systems may necessitate further refinements of the categories and guilds, particularly in relation to freshwater fishes, notably the Siluriformes, which dominate many north and north-east South American systems. The extent to which South American studies contribute to discussions and paradigms of connectivity and estuarine dependence is summarized, but work on these topics has only just begun. The anthropogenic issue of pollution, particularly in relation to heavy metals and fishes and fisheries in estuaries is more advanced, but the possible effects of climate change have barely been addressed. Studies around conservation and management are briefly reviewed and the extent to which key factors are being addressed is examined. Although there have been major advances in knowledge of estuarine fishes in South America, information is patchy, with most data from relatively few systems in Argentina and Brazil. PMID- 26864606 TI - Palladium-catalyzed paraformaldehyde insertion: a three-component synthesis of benzofurans. AB - An efficient procedure for 2-aroylbenzofuran preparation from 2-bromophenols, phenacyl bromides and paraformaldehyde is described. The cheap and stable paraformaldehyde served as the carbon source via an in situ formylation reaction. PMID- 26864607 TI - Stability of nicotinate and dodecyl sulfate in a Lewis acidic ionic liquid for aluminum electroplating and characterization of their degradation products. AB - Plating bath additives are essential for optimization of the morphology of electroplated layers. The ionic liquid 1-ethyl-3-methylimidazolium (EMIM) chloride plus 1.5 mol equivalents of AlCl3 has great potential for electroplating of aluminum. In this study, the chemical and electrochemical stability of the additives EMIM-nicotinate and sodium dodecyl sulfate and their effect on the stability of EMIM was investigated and analyzed. Nicotinate and its electrochemical decomposition product beta-picoline could be detected and we show with a single HPLC-UV-MS method that EMIM is not affected by the decomposition of this additive. An adapted standard HPLC-UV-MS method together with GC-MS and ion chromatography was used to analyze the decomposition products of SDS and possible realkylation products of EMIM. Several volatile medium and short chain-length alkanes as well as sulfate ions have been found as decomposition products of SDS. Alkenium ions formed as intermediates during the decomposition of SDS realkylate EMIM to produce mono- up to pentasubstituted alkyl-imidazoles. A reaction pathway involving Wagner-Meerwein rearrangements and Friedel-Crafts alkylations has been suggested to account for the formation of the detected products. PMID- 26864608 TI - Alleviation of proton toxicity by nitrate uptake specifically depends on nitrate transporter 1.1 in Arabidopsis. AB - Protons in acid soil are highly rhizotoxic to plants, but the mechanism of tolerance of plants to protons is largely unknown. Nitrate uptake by root cells is accompanied by the uptake of protons. Therefore, nitrate uptake transporters (NRTs) may be involved in plant tolerance to proton toxicity. We investigated the root nitrate uptake response to proton stress in Arabidopsis and its association with proton tolerance using NRT-related mutants and pharmacological methods. Lack of NRT1.1 in knockout nrt1.1 mutants led to impaired proton tolerance in nitrate sufficient growth medium, whereas no difference was seen between wild-type plants and NRT1.2-, NRT2.1-, NRT2.2-, and NRT2.4-null mutants. Another nrt1.1 point mutant, which is defective in nitrate uptake but has a normal nitrate-sensing function, also had impaired proton tolerance compared with the wild-type plant. Furthermore, proton stress induced NRT1.1-mediated nitrate uptake. These results indicate that NRT1.1-conferred proton tolerance depends on nitrate uptake activity. In addition, the rooting medium was alkalified by wild-type plants, but not by knockout nrt1.1 mutants, and in pH-buffered medium, there were no differences in proton tolerance between wild-type plants and knockout nrt1.1 mutants. We conclude that NRT1.1-mediated nitrate uptake plays a crucial role in plant proton tolerance by alkalifying the rhizosphere. PMID- 26864609 TI - A Luminescent Metal-Organic Framework Thermometer with Intrinsic Dual Emission from Organic Lumophores. AB - A new mixed-ligand metal-organic framework (MOF), ZnATZ-BTB, has been constructed as a luminescent ratiometric thermometer by making use of the intrinsic dual emission at cryogenic temperatures. Its twofold interpenetrated network promotes the Dexter energy transfer (DET) between the mixed organic lumophores. The temperature-dependent luminescent behavior arises from the thermal equilibrium between two separated excited states coupled by DET, which is confirmed by Boltzmann distribution fitting. The small excited-state energy gap allows ZnATZ BTB to measure and visualize cryogenic temperatures (30-130 K) with significantly high relative sensitivity (up to 5.29% K(-1) at 30 K). Moreover, it is the first example of a ratiometric MOF thermometer the dual emitting sources of which are widely applicable mixed organic ligands, opening up new opportunities for designing such devices. PMID- 26864610 TI - The clinical dilemma and management of red cell autoantibodies. PMID- 26864611 TI - Optoelectronic Properties of Solution Grown ZnO n-p or p-n Core-Shell Nanowire Arrays. AB - Sb doped ZnO nanowires grown using the low-temperature hydrothermal method have the longest reported p-type stability of over 18 months. Using this growth system, bulk homojunction films of core-shell ZnO nanowires were synthesized with either n or p-type cores and the oppositely doped shell. Extensive transmission electron microscopy (TEM) characterization showed that the nanowires remain single crystalline, and the previously reported signs of doping remain intact. The electronic properties of these films were measured, and ultraviolet photodetection was observed. This growth technique could serve as the basis for other optoelectronic devices based on ZnO such as light emitting diodes and photovoltaics. PMID- 26864612 TI - Extreme genetic diversity in asexual grass thrips populations. AB - The continuous generation of genetic variation has been proposed as one of the main factors explaining the maintenance of sexual reproduction in nature. However, populations of asexual individuals may attain high levels of genetic diversity through within-lineage diversification, replicate transitions to asexuality from sexual ancestors and migration. How these mechanisms affect genetic variation in populations of closely related sexual and asexual taxa can therefore provide insights into the role of genetic diversity for the maintenance of sexual reproduction. Here, we evaluate patterns of intra- and interpopulation genetic diversity in sexual and asexual populations of Aptinothrips rufus grass thrips. Asexual A. rufus populations are found throughout the world, whereas sexual populations appear to be confined to few locations in the Mediterranean region. We found that asexual A. rufus populations are characterized by extremely high levels of genetic diversity, both in comparison with their sexual relatives and in comparison with other asexual species. Migration is extensive among asexual populations over large geographic distances, whereas close sexual populations are strongly isolated from each other. The combination of extensive migration with replicate evolution of asexual lineages, and a past demographic expansion in at least one of them, generated high local clone diversities in A. rufus. These high clone diversities in asexual populations may mimic certain benefits conferred by sex via genetic diversity and could help explain the extreme success of asexual A. rufus populations. PMID- 26864614 TI - Influence of Skeletal and Local Bone Density on Dental Implant Stability in Patients with Osteoporosis. AB - BACKGROUND AND PURPOSE: Osteoporosis is a major skeletal disease affecting millions of people worldwide. Recent studies claim that patients with osteoporosis do not have a higher risk of early implant failure compared to non osteoporotic patients. The aim of this study was to assess the effect of skeletal osteoporosis and local bone density on initial dental implant stability. MATERIALS AND METHODS: Seventy-three patients were recruited and were assigned (based on a Dual-energy X-ray Absorptiometry scan) to either the osteoporosis (Opr), osteopenia (Opn), or control (C) group. Forty nine of the 73 patients received dental implants and had implant stability measured by means of resonance frequency analysis (RFA) at implant placement and at prosthetic abutment placement. On the computerized tomography scans, the cortical thickness and the bone density (Hounsfield Units) at the sites of implant placement were measured. RESULTS: At implant placement, primary stability was on average lower in group Opr (63.3 +/- 10.3 ISQ) than in group Opn (65.3 +/- 7.5 implant stability qutient (ISQ)), and group C (66.7 +/- 8.7 ISQ). At abutment placement, a similar trend was observed: group Opr (66.4 +/- 9.5 ISQ) scored lower than group Opn (70.7 +/- 7.8 ISQ), while the highest average was for group C (72.2 +/- 7.2 ISQ). The difference between groups Opr and C was significant. Implant length and diameter did not have a significant effect on implant stability as measured with RFA. A significant correlation was found between local bone density and implant stability for all regions of interest. CONCLUSIONS: Implant stability seems to be influenced by both local and skeletal bone densities. The lower stability scores in patient with skeletal osteoporosis reinforce the recommendations that safe protocols and longer healing times could be recommended when treating those patients with dental implants. PMID- 26864613 TI - Discriminant musculo-skeletal leg characteristics between sprint and endurance elite Caucasian runners. AB - Excellence in either sprinting or endurance running requires specific musculo skeletal characteristics of the legs. This study aims to investigate the morphology of the leg of sprinters and endurance runners of Caucasian ethnicity. Eight male sprinters and 11 male endurance runners volunteered to participate in this cross-sectional study. They underwent magnetic resonance imaging and after data collection, digital reconstruction was done to calculate muscle volumes and bone lengths. Sprinters have a higher total upper leg volume compared to endurance runners (7340 vs 6265 cm3 ). Specifically, the rectus femoris, vastus lateralis, and hamstrings showed significantly higher muscle volumes in the sprint group. For the lower leg, only a higher muscle volume was found in the gastrocnemius lateralis for the sprinters. No differences were found in muscle volume distribution, center of mass in the different muscles, or relative bone lengths. There was a significant positive correlation between ratio hamstrings/quadriceps volume and best running performance in the sprint group. Sprinters and endurance runners of Caucasian ethnicity showed the greatest distinctions in muscle volumes, rather than in muscle distributions or skeletal measures. Sprinters show higher volumes in mainly the proximal and lateral leg muscles than endurance runners. PMID- 26864616 TI - Mussel-inspired one-pot synthesis of transition metal and nitrogen co-doped carbon (M/N-C) as efficient oxygen catalysts for Zn-air batteries. AB - Transition metal and nitrogen co-doping into carbon is an effective approach to promote the catalytic activities towards the oxygen reduction reaction (ORR) and/or oxygen evolution reaction (OER) in the resultant electrocatalysts, M/N-C. The preparation of such catalysts, however, is often complicated and in low yield. Herein we report a robust approach for easy synthesis of M/N-C hybrids in high yield, which includes a mussel-inspired polymerization reaction at room temperature and a subsequent carbonization process. With the introduction of selected transition metal salts into an aqueous solution of dopamine (DA), the obtained mixture self-polymerizes to form metal-containing polydopamine (M-PDA) composites, e.g. Co-PDA, Ni-PDA and Fe-PDA. Upon carbonization at elevated temperatures, these metal-containing composites were converted into M/N-C, i.e. Co-PDA-C, Ni-PDA-C and Fe-PDA-C, respectively, whose morphologies, chemical compositions, and electrochemical performances were fully studied. Enhanced ORR activities were found in all the obtained hybrids, with Co-PDA-C standing out as the most promising catalyst with excellent stability and catalytic activities towards both ORR and OER. This was further proven in Zn-air batteries (ZnABs) in terms of discharge voltage stability and cycling performance. At a discharge charge current density of 2 mA cm(-2) and 1 h per cycle, the Co-PDA-C based ZnABs were able to steadily cycle up to 500 cycles with only a small increase in the discharge-charge voltage gap which notably outperformed Pt/C; at a discharge current density of 5 mA cm(-2), the battery continuously discharged for more than 540 h with the discharge voltage above 1 V and a voltage drop rate of merely 0.37 mV h(-1). With the simplicity and scalability of the synthetic approach and remarkable battery performances, the Co-PDA-C hybrid catalyst is anticipated to play an important role in practical ZnABs. PMID- 26864615 TI - Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine. AB - BACKGROUND: Biological significance of ELK1, a transcriptional factor whose phosphorylation is necessary for c-fos proto-oncogene activation, in prostate cancer remains far from fully understood. In this study, we aim to investigate the role of ELK1 in tumor growth as well as the efficacy of a selective alpha1A adrenergic blocker, silodosin, in ELK1 activity in prostate cancer cells. METHODS: We first immunohistochemically determined the levels of phospho-ELK1 (p ELK1) expression in radical prostatectomy specimens. We then assessed the effects of ELK1 knockdown via short hairpin RNA and silodosin on cell proliferation, migration, and invasion in prostate cancer lines. RESULTS: The levels of p-ELK1 expression were significantly higher in carcinoma than in benign (P < 0.001) or high-grade prostatic intraepithelial neoplasia (HGPIN) (P = 0.002) as well as in HGPIN than in benign (P < 0.001). Kaplan-Meier and log-rank tests revealed that moderate-strong positivity of p-ELK1 in carcinomas tended to correlate with biochemical recurrence after radical prostatectomy (P = 0.098). In PC3 and DU145 expressing ELK1 (mRNA/protein) but no androgen receptor (AR), ELK1 silencing resulted in considerable decreases in the expression of c-fos as well as in cell migration/invasion and matrix metalloproteinase-2 expression, but not in cell viability. Silodosin treatment reduced the expression/activity of ELK1 in these cells as well as the viability of AR-positive LNCaP and C4-2 cells and the migration of both AR-positive and AR-negative cells, but not the viability of AR negative or ELK1-negative cells. Interestingly, silodosin significantly increased sensitivity to gemcitabine, but not to cisplatin or docetaxel, even in AR negative cells. CONCLUSIONS: ELK1 is likely to be activated in prostate cancer cells and promote tumor progression. Furthermore, silodosin that inactivates ELK1 in prostate cancer cells not only inhibits their growth but also enhances the cytotoxic activity of gemcitabine. Thus, ELK1 inhibition has the potential of being a therapeutic approach for prostate cancer. PMID- 26864617 TI - Epidemiology of Surgical Site Infection in a Community Hospital Network. AB - OBJECTIVE: To describe the epidemiology of complex surgical site infection (SSI) following commonly performed surgical procedures in community hospitals and to characterize trends of SSI prevalence rates over time for MRSA and other common pathogens METHODS: We prospectively collected SSI data at 29 community hospitals in the southeastern United States from 2008 through 2012. We determined the overall prevalence rates of SSI for commonly performed procedures during this 5 year study period. For each year of the study, we then calculated prevalence rates of SSI stratified by causative organism. We created log-binomial regression models to analyze trends of SSI prevalence over time for all pathogens combined and specifically for MRSA. RESULTS: A total of 3,988 complex SSIs occurred following 532,694 procedures (prevalence rate, 0.7 infections per 100 procedures). SSIs occurred most frequently after small bowel surgery, peripheral vascular bypass surgery, and colon surgery. Staphylococcus aureus was the most common pathogen. The prevalence rate of SSI decreased from 0.76 infections per 100 procedures in 2008 to 0.69 infections per 100 procedures in 2012 (prevalence rate ratio [PRR], 0.90; 95% confidence interval [CI], 0.82-1.00). A more substantial decrease in MRSA SSI (PRR, 0.69; 95% CI, 0.54-0.89) was largely responsible for this overall trend. CONCLUSIONS: The prevalence of MRSA SSI decreased from 2008 to 2012 in our network of community hospitals. This decrease in MRSA SSI prevalence led to an overall decrease in SSI prevalence over the study period. PMID- 26864618 TI - Recent Trends in the Prevalence of Marijuana Use and Associated Disorders in the United States. PMID- 26864619 TI - Oxidative stress and antioxidative systems: recipes for successful data collection and interpretation. AB - Oxidative stress and reactive oxygen species (ROS) are common to many fundamental responses of plants. Enormous and ever-growing interest has focused on this research area, leading to an extensive literature that documents the tremendous progress made in recent years. As in other areas of plant biology, advances have been greatly facilitated by developments in genomics-dependent technologies and the application of interdisciplinary techniques that generate information at multiple levels. At the same time, advances in understanding ROS are fundamentally reliant on the use of biochemical and cell biology techniques that are specific to the study of oxidative stress. It is therefore timely to revisit these approaches with the aim of providing a guide to convenient methods and assisting interested researchers in avoiding potential pitfalls. Our critical overview of currently popular methodologies includes a detailed discussion of approaches used to generate oxidative stress, measurements of ROS themselves, determination of major antioxidant metabolites, assays of antioxidative enzymes and marker transcripts for oxidative stress. We consider the applicability of metabolomics, proteomics and transcriptomics approaches and discuss markers such as damage to DNA and RNA. Our discussion of current methodologies is firmly anchored to future technological developments within this popular research field. PMID- 26864620 TI - Hydrochlorothiazide Induced Lichen Planus in the Emergency Department. AB - Lichen planus (LP) is a mucocutaneous inflammatory disease that involves papulosquamous eruption of the skin, scalp, nails, and mucous membranes. This uncommon condition has a higher prevalence in African Americans and females. Women accounts for 50% of cutaneous LP (CLP) and 60% to 75% of oral LP (OLP) cases. Diagnosis is centered around clinical presentation. Patient evaluation requires a comprehensive physical examination to identify any potential sites of involvement. LP is usually described by the "Six P's": planar, purple, polygonal, pruritic, papules, and plaques. Drug-induced LP, or lichenoid drug reactions, is uncommon and usually indiscernible from other forms of LP. Lichenoid drug reactions exhibit parakeratosis, dermal infiltrates of eosinophils, or perivascular lymphocytic infiltrates affecting the reticular dermis. An extended time interval between the initiation of drug to the onset of symptoms usually does not exclude potential diagnosis of a lichenoid drug reaction. We describe a case of hydrochlorothiazide-induced LP without prolonged exposure to sunlight diagnosed in the emergency department (ED). In this case, a pharmacist-conducted medication reconciliation played an integral role in accurately recognizing this adverse drug reaction. Our case report adds to the limited available literature on the topic, most of which originated more than 30 years ago. PMID- 26864621 TI - Salvage Treatment of Mucormycosis Post-Liver Transplant With Posaconazole During Sirolimus Maintenance Immunosuppression. AB - We describe the first successful case of posaconazole salvage therapy for mucormycosis with concomitant sirolimus (SRL) maintenance immunosuppression following liver transplantation, despite black box drug interaction following intolerance to first-line tacrolimus and amphotericin due to nephrotoxicity and neurotoxicity. This case describes a 55-year-old female who developed rhinocerebral mucormycosis 108 days after liver transplantation. After 3 months of posaconazole therapy, the patient remains free of disease at 3 years posttransplant. This case report illustrates successful resolution of mucormycosis without SRL toxicity to resolve nephrotoxicity of long-term amphotericin on top of already nephrotoxic immunosuppression. With higher bioavailability of recently FDA-approved posaconazole delayed release tablets, this azole may be a therapeutic option for transplant patients who need to remain on CYP3A4-metabolized immunosuppressive agents. PMID- 26864622 TI - Liver innate immune cells and insulin resistance: the multiple facets of Kupffer cells. AB - Obesity, which affects 600 million adults worldwide, is a major risk factor for type 2 diabetes (T2D) and insulin resistance. Current therapies for these metabolic disorders include weight management by lifestyle intervention or bariatric surgery and pharmacological treatment with the aim of regulating blood glucose. Probably because of their short-term effectiveness, these therapies have not been able to stop the rapidly rising prevalence of T2D over the past decades, highlighting an urgent need to develop new therapeutic strategies. The role of immune cells, such as macrophages, in insulin resistance has been extensively studied. Major advances have been made to elucidate the role of adipose tissue macrophages in these pathogeneses. Recently, anti-inflammatory drugs have been suggested as an alternative treatment for T2D, and clinical trials of these agents are currently ongoing. In addition, results of previous clinical trials using antibodies against inflammatory cytokines, which showed modest effects, are now being rigorously re-evaluated. However, it is still unclear how liver macrophages [termed Kupffer cells (KCs)], which constitute the major source of macrophages in the body, contribute to the development of insulin resistance. In this review, we will discuss the present understanding of the role of liver immune cells in the development of insulin resistance. We will particularly focus on KCs, which could represent an attractive target for the treatment of metabolic diseases. PMID- 26864623 TI - LKB1 kinase-dependent and -independent defects disrupt polarity and adhesion signaling to drive collagen remodeling during invasion. AB - LKB1 is a serine/threonine kinase and a commonly mutated gene in lung adenocarcinoma. The majority of LKB1 mutations are truncations that disrupt its kinase activity and remove its C-terminal domain (CTD). Because LKB1 inactivation drives cancer metastasis in mice and leads to aberrant cell invasion in vitro, we sought to determine how compromised LKB1 function affects lung cancer cell polarity and invasion. Using three-dimensional models, we show that LKB1 kinase activity is essential for focal adhesion kinase-mediated cell adhesion and subsequent collagen remodeling but not cell polarity. Instead, cell polarity is overseen by the kinase-independent function of its CTD and more specifically its farnesylation. This occurs through a mesenchymal-amoeboid morphological switch that signals through the Rho-GTPase RhoA. These data suggest that a combination of kinase-dependent and -independent defects by LKB1 inactivation creates a uniquely invasive cell with aberrant polarity and adhesion signaling that drives invasion into the microenvironment. PMID- 26864624 TI - RCC1-dependent activation of Ran accelerates cell cycle and DNA repair, inhibiting DNA damage-induced cell senescence. AB - The coordination of cell cycle progression with the repair of DNA damage supports the genomic integrity of dividing cells. The function of many factors involved in DNA damage response (DDR) and the cell cycle depends on their Ran GTPase regulated nuclear-cytoplasmic transport (NCT). The loading of Ran with GTP, which is mediated by RCC1, the guanine nucleotide exchange factor for Ran, is critical for NCT activity. However, the role of RCC1 or Ran?GTP in promoting cell proliferation or DDR is not clear. We show that RCC1 overexpression in normal cells increased cellular Ran?GTP levels and accelerated the cell cycle and DNA damage repair. As a result, normal cells overexpressing RCC1 evaded DNA damage induced cell cycle arrest and senescence, mimicking colorectal carcinoma cells with high endogenous RCC1 levels. The RCC1-induced inhibition of senescence required Ran and exportin 1 and involved the activation of importin beta dependent nuclear import of 53BP1, a large NCT cargo. Our results indicate that changes in the activity of the Ran?GTP-regulated NCT modulate the rate of the cell cycle and the efficiency of DNA repair. Through the essential role of RCC1 in regulation of cellular Ran?GTP levels and NCT, RCC1 expression enables the proliferation of cells that sustain DNA damage. PMID- 26864626 TI - Structure and function of outer dynein arm intermediate and light chain complex. AB - The outer dynein arm (ODA) is a molecular complex that drives the beating motion of cilia/flagella. Chlamydomonas ODA is composed of three heavy chains (HCs), two ICs, and 11 light chains (LCs). Although the three-dimensional (3D) structure of the whole ODA complex has been investigated, the 3D configurations of the ICs and LCs are largely unknown. Here we identified the 3D positions of the two ICs and three LCs using cryo-electron tomography and structural labeling. We found that these ICs and LCs were all localized at the root of the outer-inner dynein (OID) linker, designated the ODA-Beak complex. Of interest, the coiled-coil domain of IC2 extended from the ODA-Beak to the outer surface of ODA. Furthermore, we investigated the molecular mechanisms of how the OID linker transmits signals to the ODA-Beak, by manipulating the interaction within the OID linker using a chemically induced dimerization system. We showed that the cross-linking of the OID linker strongly suppresses flagellar motility in vivo. These results suggest that the ICs and LCs of the ODA form the ODA-Beak, which may be involved in mechanosignaling from the OID linker to the HCs. PMID- 26864625 TI - Confined diffusion of transmembrane proteins and lipids induced by the same actin meshwork lining the plasma membrane. AB - The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed "hop diffusion") for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion. PMID- 26864627 TI - Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion. AB - The apical brush border membrane (BBM) of intestinal epithelial cells forms a highly structured and dynamic environmental interface that serves to regulate cellular physiology and block invasion by intestinal microbes and their products. How the BBM dynamically responds to pathogenic and commensal bacterial signals can define intestinal homeostasis and immune function. We previously found that in model intestinal epithelium, the conversion of apical membrane sphingomyelin to ceramide by exogenous bacterial sphingomyelinase (SMase) protected against the endocytosis and toxicity of cholera toxin. Here we elucidate a mechanism of action by showing that SMase induces a dramatic, reversible, RhoA-dependent alteration of the apical cortical F-actin network. Accumulation of apical membrane ceramide is necessary and sufficient to induce the actin phenotype, and this coincides with altered membrane structure and augmented innate immune function as evidenced by resistance to invasion by Salmonella. PMID- 26864628 TI - Two distinct myosin II populations coordinate ovulatory contraction of the myoepithelial sheath in the Caenorhabditis elegans somatic gonad. AB - The myoepithelial sheath in the somatic gonad of the nematode Caenorhabditis elegans has nonstriated contractile actomyosin networks that produce highly coordinated contractility for ovulation of mature oocytes. Two myosin heavy chains are expressed in the myoepithelial sheath, which are also expressed in the body-wall striated muscle. The troponin/tropomyosin system is also present and essential for ovulation. Therefore, although the myoepithelial sheath has smooth muscle-like contractile apparatuses, it has a striated muscle-like regulatory mechanism through troponin/tropomyosin. Here we report that the myoepithelial sheath has a distinct myosin population containing nonmuscle myosin II isoforms, which is regulated by phosphorylation and essential for ovulation. MLC-4, a nonmuscle myosin regulatory light chain, localizes to small punctate structures and does not colocalize with large, needle-like myosin filaments containing MYO 3, a striated-muscle myosin isoform. RNA interference of MLC-4, as well as of its upstream regulators, LET-502 (Rho-associated coiled-coil forming kinase) and MEL 11 (a myosin-binding subunit of myosin phosphatase), impairs ovulation. Expression of a phosphomimetic MLC-4 mutant mimicking a constitutively active state also impairs ovulation. A striated-muscle myosin (UNC-54) appears to provide partially compensatory contractility. Thus the results indicate that the two spatially distinct myosin II populations coordinately regulate ovulatory contraction of the myoepithelial sheath. PMID- 26864630 TI - Allogeneic Haematopoietic Stem Cell Transplantation for Patients with Cutaneous T cell Lymphoma. PMID- 26864629 TI - Phosphoinositide kinase signaling controls ER-PM cross-talk. AB - Membrane lipid dynamics must be precisely regulated for normal cellular function, and disruptions in lipid homeostasis are linked to the progression of several diseases. However, little is known about the sensory mechanisms for detecting membrane composition and how lipid metabolism is regulated in response to membrane stress. We find that phosphoinositide (PI) kinase signaling controls a conserved PDK-TORC2-Akt signaling cascade as part of a homeostasis network that allows the endoplasmic reticulum (ER) to modulate essential responses, including Ca(2+)-regulated lipid biogenesis, upon plasma membrane (PM) stress. Furthermore, loss of ER-PM junctions impairs this protective response, leading to PM integrity defects upon heat stress. Thus PI kinase-mediated ER-PM cross-talk comprises a regulatory system that ensures cellular integrity under membrane stress conditions. PMID- 26864632 TI - Fundamental aspects in surface self-assembly: theoretical implications of molecular polarity and shape. AB - We investigate fundamental aspects of structure formation in molecular self assembly, by examining the emergence of order upon adsorption of a series of model molecules. It is known that strongly polar diatomic molecules form three dimensional crystals in the absence of a substrate. This tendency can be disrupted upon assembly on a solid surface, and various other types of order may arise. Depending on the relative strength of the interactions, disordered phases, two-dimensional crystals commensurate to the surface, and unmodified crystals were observed upon adsorption of simple dipoles in the present work. Introduction of steric features, in the form of a longer backbone or substituents external to the polar pair, led to even richer phase diagrams. The formation of two dimensional phases with nematic (parallel) or antiparallel alignment was accomplished by altering the polarity of the end groups on needle-like molecules, whereas embedded charged groups made two-dimensional structure unstable for even very long molecules. These molecules preferred to align in long, often desorbed, molecular wires. The wealth of phases observed here parallel the results of experimental systematic or incidental studies of the relationships between molecular interactions and self-assembled patterns, and provide some insight into the molecular handles that self-assembly researchers can wield to guide the process towards a desired structural outcome. PMID- 26864631 TI - Nuclear magnetic resonance analysis of the conformational state of cancer mutant of fibroblast growth factor receptor 1 tyrosine kinase domain. AB - Tyrosine kinases are key enzymes that play critical roles in growth signaling, the abnormal activation of which is associated with various human cancers. Activation of tyrosine kinases is mediated by tyrosine phosphorylation in the activation-loop, which transforms the catalytic domain to the active state conformation. Cancer mutations are supposed to transform the conformation of the catalytic domain into the active-form independent of the phosphorylation state of the activation-loop. Here, we report structural and biophysical analyses of cancer mutations of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1). Based on the nuclear magnetic resonance analyses, phosphorylation of the activation-loop exhibited cooperative structural transition in the activation-loop, C-helix and P-loop regions, whereas cancer mutations induced structural transformation at either one or two of these regions. PMID- 26864633 TI - Increasing the information rates of optical communications via coded modulation: a study of transceiver performance. AB - Optical fibre underpins the global communications infrastructure and has experienced an astonishing evolution over the past four decades, with current commercial systems transmitting data rates in excess of 10 Tb/s over a single fibre core. The continuation of this dramatic growth in throughput has become constrained due to a power dependent nonlinear distortion arising from a phenomenon known as the Kerr effect. The mitigation of fibre nonlinearities is an area of intense research. However, even in the absence of nonlinear distortion, the practical limit on the transmission throughput of a single fibre core is dominated by the finite signal-to-noise ratio (SNR) afforded by current state-of the-art coherent optical transceivers. Therefore, the key to maximising the number of information bits that can be reliably transmitted over a fibre channel hinges on the simultaneous optimisation of the modulation format and code rate, based on the SNR achieved at the receiver. In this work, we use an information theoretic approach based on the mutual information and the generalised mutual information to characterise a state-of-the-art dual polarisation m-ary quadrature amplitude modulation transceiver and subsequently apply this methodology to a 15 carrier super-channel to achieve the highest throughput (1.125 Tb/s) ever recorded using a single coherent receiver. PMID- 26864634 TI - Risk Factors for Silent Lacunar Infarction in Patients with Transient Ischemic Attack. AB - BACKGROUND Lacunar infarctions represent 25% of ischemic strokes. Lacunar stroke and transient ischemic attack (TIA) share a number of symptoms. This study aimed to assess the potential risk factors for lacunar infarction in patients with TIA. MATERIAL AND METHODS This was a retrospective study performed at the Beijing Military General Hospital in patients with TIA admitted between March 2010 and December 2011. Patients were grouped according to lacunar vs. no lacunar infarction. All patients were diagnosed using diffusion-weighted imaging (DWI) on brain magnetic resonance imaging (MRI). Brain angiography (computed tomography and MRI) was used to measure intracranial stenosis. Carotid artery stenosis was measured by ultrasound. RESULTS Patients with TIA and lacunar infarction (n=298) were older than those without lacunar infarction (n=157) (69.4+/-10.0 vs. 58.9+/ 9.0 years, P<0.001) and showed a higher frequency of males (51.7% vs. 41.4%, P=0.037), hypertension (75.3% vs. 45.9%, P<0.001), diabetes (32.6% vs. 21.0%, P=0.010), hyperlipidemia (53.4% vs. 29.3%, P<0.001), carotid stenosis (73.2% vs. 40.1%, P<0.001), and intracranial stenosis (55.6% vs. 31.9%, P<0.001), but a lower frequency of alcohol drinking (8.1% vs. 14.0%, P=0.045). Lacunar infarction mostly involved the anterior circulation (62.8%). Multivariate analysis showed that age (odds ratio (OR)=1.085, 95% confidence interval (95%CI): 1.054-1.117, P<0.001), hypertension (OR=1.738, 95%CI: 1.041-2.903, P=0.035), hyperlipidemia (OR=2.169, 95%CI: 1.307-3.601, P=0.003), and carotid stenosis (OR=1.878, 95%CI: 1.099-3.206, P=0.021) were independently associated with lacunar infarction. CONCLUSIONS Age, hypertension, hyperlipidemia, and carotid stenosis were independently associated with silent lacunar infarction in patients with TIA. PMID- 26864635 TI - Advanced intermediate temperature sodium-nickel chloride batteries with ultra high energy density. AB - Sodium-metal halide batteries have been considered as one of the more attractive technologies for stationary electrical energy storage, however, they are not used for broader applications despite their relatively well-known redox system. One of the roadblocks hindering market penetration is the high-operating temperature. Here we demonstrate that planar sodium-nickel chloride batteries can be operated at an intermediate temperature of 190 degrees C with ultra-high energy density. A specific energy density of 350 Wh kg(-1), higher than that of conventional tubular sodium-nickel chloride batteries (280 degrees C), is obtained for planar sodium-nickel chloride batteries operated at 190 degrees C over a long-term cell test (1,000 cycles), and it attributed to the slower particle growth of the cathode materials at the lower operating temperature. Results reported here demonstrate that planar sodium-nickel chloride batteries operated at an intermediate temperature could greatly benefit this traditional energy storage technology by improving battery energy density, cycle life and reducing material costs. PMID- 26864637 TI - C15065. Chemical Constituents of Plants from the Genus Ixora. AB - Ixora is a genus of ca. 400 species in the family Rubiaceae, mainly distributing in tropical Asia, Africa and Oceania, with 19 species being endemic to South China [1]. The plants of the genus usually have small beautiful flowers, being easily cultured as common roadside and garden trees. The leaves, flowers, stems and roots of several species have been used in traditional medicine to treat various ailments. For example, the leaves and stems of I. coccinea are widely used in traditional Sudanese and Ayurvedic medicinal systems for the treatment of diarrhea, fever, headache, skin diseases, eye trouble, wounds, sores and ulcers [2]. The flowers and leaves of I. javanica are used as a sedative stomachic tonic, intestinal antiseptic and as astringent. Externally the flower parts are used to heal sores and chronic ulcers [3]. This article is protected by copyright. All rights reserved. PMID- 26864636 TI - A Trans-omics Mathematical Analysis Reveals Novel Functions of the Ornithine Metabolic Pathway in Cancer Stem Cells. AB - Bioinformatics and computational modelling are expected to offer innovative approaches in human medical science. In the present study, we performed computational analyses and made predictions using transcriptome and metabolome datasets obtained from fluorescence-based visualisations of chemotherapy resistant cancer stem cells (CSCs) in the human oesophagus. This approach revealed an uncharacterized role for the ornithine metabolic pathway in the survival of chemotherapy-resistant CSCs. The present study fastens this rationale for further characterisation that may lead to the discovery of innovative drugs against robust CSCs. PMID- 26864638 TI - Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review. AB - Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors. PMID- 26864639 TI - An Enantioselective Assembly of Dihydropyranones through an NHC/LiCl-Mediated in situ Activation of alpha,beta-Unsaturated Carboxylic Acids. AB - A straightforward N-heterocyclic carbene (NHC)/LiCl-mediated synthesis of dihydropyranones from alpha,beta-unsaturated carboxylic acids and 1,3-dicarbonyl compounds was realized through the in situ activation strategy. The key advantages of this protocol include ready availability and high stability of starting materials, good yields, and excellent enantioselectivity. PMID- 26864640 TI - MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4. AB - Pancreatic cancer patients are often resistant to chemotherapy treatment, which results in poor prognosis. The objective of this study was to delineate the mechanism by which miR-21 induces drug resistance to 5-fluorouracil (5-FU) in human pancreatic cancer cells (PATU8988 and PANC-1). We report that PATU8988 cells resistant to 5-FU express high levels of miR-21 in comparison to sensitive primary PATU8988 cells. Suppression of miR-21 expression in 5-Fu-resistant PATU8988 cells can alleviate its 5-FU resistance. Meanwhile, lentiviral vector mediated overexpression of miR-21 not only conferred resistance to 5-FU but also promoted proliferation, migration, and invasion of PATU8988 and PANC-1 cells. The proresistance effects of miR-21 were attributed to the attenuated expression of tumor suppressor genes, including PTEN and PDCD4. Overexpression of PTEN and PDCD4 antagonized miR-21-induced resistance to 5-FU and migration activity. Our work demonstrates that miR-21 can confer drug resistance to 5-FU in pancreatic cancer cells by regulating the expression of tumor suppressor genes, as the target genes of miR-21, PTEN and PDCD4 can rescue 5-FU sensitivity and the phenotypic characteristics disrupted by miR-21. PMID- 26864641 TI - Proline and lysine residues provide modulatory switches in amyloid formation: Insights from prion protein. AB - Amyloidogenic proteins have an increased propensity to reorganize into the highly structured, beta sheet rich structures that characterize amyloid. The probability of attaining these highly structured assemblies is influenced by multiple factors, including amino acid composition and environmental conditions. Evolutionary selection for amino acid sequences that prevent amyloid formation could further modulate amyloid-forming propensity. Indeed, we have recently identified specific proline and lysine residues, contained within a highly conserved central region of prion protein (PrP), that impede PrP amyloid formation in vitro. These prolines are mutated in certain forms of the human familial genetic disease, Gerstmann-Straussler-Schneiker (GSS) syndrome. Here, I discuss the influence of these proline and lysine residues on PrP amyloid formation and how such anti-amyloidogenic primary amino acid sequences might be modulated to influence protein amyloidogenicity. PMID- 26864642 TI - Right Ventricular Longitudinal Strain Measures Independently Predict Chronic Heart Failure Mortality. AB - The assessment of right ventricular (RV) function still remains a challenge. Two dimensional (2D) speckle tracking has recently been proposed to evaluate right ventricular function by analyzing myocardial deformation. The aim of this study was to evaluate the role of 2D systolic strain measures of RV in predicting mortality in patients with chronic heart failure (HF). We enrolled 332 outpatients in a stable clinical condition and in conventional therapy. A right ventricular-focused four-chamber view was analyzed by 2D speckle tracking to evaluate the global longitudinal strain of RV (RV-GLS) and the strain of RV free wall (RV-fwLS). During a mean follow-up of 36 +/- 26 months, 64 patients died. Both RV-GLS and RV-fwLS were associated with all-cause mortality in univariate (HR: 1.16; 95% CI: 1.10-1.23; P < 0.001; C-index: 0.72; and HR: 1.10; 95% CI: 1.06-1.15; P < 0.001; C-index: 0.68, respectively) as well as multivariate analysis (HR: 1.13; 95% CI: 1.05-1.21; P:0.001; C-index: 0.85; and HR: 1.07; 95% CI: 1.02-1.12; P:0.004; C-index: 0.84, respectively). In conclusion, our findings demonstrate the role of RV 2D strain measures to independently predict mortality. These data highlight the clinical usefulness of this echocardiographic approach in the daily management of HF outpatients. PMID- 26864643 TI - A Focus on Chromatin Proteomics. PMID- 26864644 TI - LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta induced protein (TGFBIp). AB - More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals. PMID- 26864648 TI - Food groups consumed by infants and toddlers in urban areas of China. AB - BACKGROUND: Food consumption patterns of young children in China are not well known. OBJECTIVE: Characterised food groups consumed by infants and young children in urban China using data from the Maternal Infant Nutrition Growth (MING) study. DESIGN: One 24-h dietary recall was completed for 1,350 infants and young children (436 infants aged 6-11 months and 914 young children aged 12-35 months), who were recruited from maternal and child care centres in eight cities via face-to-face interviews with the primary caregiver. All foods, beverages and supplements reported were assigned to one of 64 food groups categorised into the following: milk and milk products, grains, vegetables, fruits, protein foods and desserts/sweets. The percentage of infants and young children consuming foods from specific food groups was calculated, regardless of the amount consumed. RESULTS: Less than half of infants consumed breast milk (47%), whereas 59% of infants consumed infant formula and 53-75% of young children consumed growing-up (fortified) milk. Rice was the number one grain food consumed after 6 months (up to 88%) and the consumption of infant cereal was low. About 50% of infants did not consume any fruits or vegetables, and 38% of young children did not consume any fruits on the day of the recall. Only 40% of all children consumed dark green leafy vegetables and even fewer consumed deep yellow vegetables. Eggs and pork were the most commonly consumed protein foods. CONCLUSIONS: The data provide important insight for developing detailed food consumption guidelines for this population group. Mothers of infants should be encouraged to continue breastfeeding after the first 6 months. Parents should be advised to offer a wide variety of vegetables and fruits daily, particularly dark green leafy and deep yellow vegetables and colourful fruits. The consumption of fortified infant cereal should be advocated to improve the iron intake of Chinese infants. PMID- 26864650 TI - Recasting a traditional laboratory practical as a "Design-your-own protocol" to teach a universal research skill. AB - Laboratory-based practical classes are a common feature of life science teaching, during which students learn how to perform experiments and generate/interpret data. Practical classes are typically instructional, concentrating on providing topic- and technique-specific skills, however to produce research-capable graduates it is also important to develop generic practical skills. To provide an opportunity for students to develop the skills needed to create bespoke protocols for experimental benchwork, a traditional practical was repurposed. Students were given a list of available resources and an experimental goal, and directed to create a bench protocol to achieve the aim (measuring the iron in hemoglobin). In a series of teaching events students received feedback from staff, and peers prototyped the protocols, before protocols were finally implemented. Graduates highlighted this exercise as one of the most important of their degrees, primarily because of the clear relevance of the skills acquired to professional practice. The exercise exemplifies a range of pedagogic principles, but arguably its most important innovation is that it repurposed a pre-existing practical. This had the benefits of automatically providing scaffolding to direct the students' thought processes, while retaining the advantages of a "discovery learning" exercise, and allowing facile adoption of the approach across the sector. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):377-380, 2016. PMID- 26864649 TI - Circulating anti-mullerian hormone as predictor of ovarian response to clomiphene citrate in women with polycystic ovary syndrome. AB - BACKGROUND: To investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. METHODS: This prospective cohort observational study included 81 anovulatory women with PCOS who underwent 213 cycles of CC ovarian stimulation. Serum AMH concentrations were measured on cycle day 3 before the commencement of CC in the first cycle, which were compared between responders and CC-resistant anovulation (CRA). Logistic regression analysis was applied to study the value of serum AMH for the prediction of ovarian responsiveness to CC stimulation. The receiver-operating characteristic (ROC) curve was used to evaluate the prognostic value of circulating AMH. MAIN OUTCOME MEASURES: Serum AMH levels. RESULTS: Women who ovulated after CC therapy had a significantly lower AMH compared with the CRA (5.34 +/- 1.97 vs.7.81 +/- 3.49, P < 0.001). There was a significant gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation (P < 0.05). In multivariate logistic regression analysis, AMH was an independent predictor of ovulation induction by CC in PCOS patients. ROC curve analysis showed AMH to be a useful predictor of ovulation induction by CC in PCOS patients, having 92 % specificity and 65 % sensitivity when the threshold AMH concentration was 7.77 ng/ml. CONCLUSION: Serum AMH may be clinically useful to predict which PCOS women are more likely to respond to CC treatment and thus to direct the selection of protocols of ovulation induction. PMID- 26864651 TI - Inhibition of Growth and Metastasis of Colon Cancer by Delivering 5-Fluorouracil loaded Pluronic P85 Copolymer Micelles. AB - Hepatic metastasis is the leading cause of mortality of colon cancer, which is still lack of an effective therapy. A new delivery system, pluronic P85 block copolymers, conveying chemotherapeutic agent 5-fluorouracil (5-Fu) for inhibiting growth and metastasis of colon cancer was designed and developed. In this study, we demonstrated that 5-Fu produce strong pesticide effect at lower doses in the present of pluronic P85 compared with control groups. The migration and invasion of HCT116 cells and RKO cells were examined and the results showed that migration and invasion capacities of HCT116 cells and RKO cells were reduced by administering 5-Fu/P85 copolymer micelles in vitro and in vivo which indicating an effectively activity. Interestingly, the content of CD133 + CXCR4+ cells in HCT116 cancer cells and RKO cells treated by 5-Fu/P85 copolymer micelles was decreased. Importantly, the epithelial-mesenchymal transition (EMT) of CD133 + CXCR4+ cells, which was strongly associated with liver metastasis of colon cancer, was also suppressed by giving 5-Fu/P85 copolymer micelles. The results indicated that 5-Fu/P85 copolymer micelles could inhibit the growth and metastasis of colon cancer, which could be attributed to the decrease of the content of CD133 + CXCR4+ cells and suppression of EMT of CD133 + CXCR4+ cells. PMID- 26864653 TI - Radiomics-based differentiation of lung disease models generated by polluted air based on X-ray computed tomography data. AB - BACKGROUND: Lung diseases (resulting from air pollution) require a widely accessible method for risk estimation and early diagnosis to ensure proper and responsive treatment. Radiomics-based fractal dimension analysis of X-ray computed tomography attenuation patterns in chest voxels of mice exposed to different air polluting agents was performed to model early stages of disease and establish differential diagnosis. METHODS: To model different types of air pollution, BALBc/ByJ mouse groups were exposed to cigarette smoke combined with ozone, sulphur dioxide gas and a control group was established. Two weeks after exposure, the frequency distributions of image voxel attenuation data were evaluated. Specific cut-off ranges were defined to group voxels by attenuation. Cut-off ranges were binarized and their spatial pattern was associated with calculated fractal dimension, then abstracted by the fractal dimension -- cut-off range mathematical function. Nonparametric Kruskal-Wallis (KW) and Mann-Whitney post hoc (MWph) tests were used. RESULTS: Each cut-off range versus fractal dimension function plot was found to contain two distinctive Gaussian curves. The ratios of the Gaussian curve parameters are considerably significant and are statistically distinguishable within the three exposure groups. CONCLUSIONS: A new radiomics evaluation method was established based on analysis of the fractal dimension of chest X-ray computed tomography data segments. The specific attenuation patterns calculated utilizing our method may diagnose and monitor certain lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, tuberculosis or lung carcinomas. PMID- 26864652 TI - Risk estimates of mortality attributed to low concentrations of ambient fine particulate matter in the Canadian community health survey cohort. AB - BACKGROUND: Understanding the shape of the relationship between long-term exposure to ambient fine particulate matter (PM2.5) concentrations and health risks is critical for health impact and risk assessment. Studies evaluating the health risks of exposure to low concentrations of PM2.5 are limited. Further, many existing studies lack individual-level information on potentially important behavioural confounding factors. METHODS: A prospective cohort study was conducted among a subset of participants in a cohort that linked respondents of the Canadian Community Health Survey to mortality (n = 299,500) with satellite derived ambient PM2.5 estimates. Participants enrolled between 2000 and 2008 were followed to date of death or December 31, 2011. Cox proportional hazards models were used to estimate hazard ratios (HRs) for mortality attributed to PM2.5 exposure, adjusted for individual-level and contextual covariates, including smoking behaviour and body mass index (BMI). RESULTS: Approximately 26,300 non accidental deaths, of which 32.5 % were due to circulatory disease and 9.1 % were due to respiratory disease, occurred during the follow-up period. Ambient PM2.5 exposures were relatively low (mean = 6.3 MUg/m(3)), yet each 10 MUg/m(3) increase in exposure was associated with increased risks of non-accidental (HR = 1.26; 95 % CI: 1.19-1.34), circulatory disease (HR = 1.19; 95 % CI: 1.07-1.31), and respiratory disease mortality (HR = 1.52; 95 % CI: 1.26-1.84) in fully adjusted models. Higher hazard ratios were observed for respiratory mortality among respondents who never smoked (HR = 1.97; 95 % CI: 1.24-3.13 vs. HR = 1.45; 95 % CI: 1.17-1.79 for ever smokers), and among obese (BMI >= 30) respondents (HR = 1.76; 95 % CI: 1.15-2.69 vs. HR = 1.41; 95 % CI: 1.04-1.91 for normal weight respondents), though differences between groups were not statistically significant. A threshold analysis for non-accidental mortality estimated a threshold concentration of 0 MUg/m(3) (+95 % CI = 4.5 MUg/m(3)). CONCLUSIONS: Increased risks of non-accidental, circulatory, and respiratory mortality were observed even at very low concentrations of ambient PM2.5. HRs were generally greater than most literature values, and adjusting for behavioural covariates served to reduce HR estimates slightly. PMID- 26864656 TI - In reference to Immunohistochemical localization of OCT2 in the cochlea of various species. PMID- 26864655 TI - BEHAVIORAL ACTIVATION AND THERAPEUTIC EXPOSURE FOR POSTTRAUMATIC STRESS DISORDER: A NONINFERIORITY TRIAL OF TREATMENT DELIVERED IN PERSON VERSUS HOME-BASED TELEHEALTH. AB - OBJECTIVE: Combat veterans returning to society with impairing mental health conditions such as PTSD and major depression (MD) report significant barriers to care related to aspects of traditional psychotherapy service delivery (e.g., stigma, travel time, and cost). Hence, alternate treatment delivery methods are needed. Home-based telehealth (HBT) is one such option; however, this delivery mode has not been compared to in person, clinic-based care for PTSD in adequately powered trials. The present study was designed to compare relative noninferiority of evidence-based psychotherapies for PTSD and MD, specifically Behavioral Activation and Therapeutic Exposure (BA-TE), when delivered via HBT versus in person, in clinic delivery. METHOD: A repeated measures (i.e., baseline, posttreatment, 3-, 6-month follow-up) randomized controlled design powered for noninferiority analyses was used to compare PTSD and MD symptom improvement in response to BA-TE delivered via HBT versus in person, in clinic conditions. Participants were 232 veterans diagnosed with full criteria or predefined subthreshold PTSD. RESULTS: PTSD and MD symptom improvement following BA-TE delivered by HBT was comparable to that of BA-TE delivered in person at posttreatment and at 3- and 12-month follow-up. CONCLUSION: Evidence-based psychotherapy for PTSD and depression can be safely and effectively delivered via HBT with clinical outcomes paralleling those of clinic-based care delivered in person. HBT, thereby, addresses barriers to care related to both logistics and stigma. PMID- 26864654 TI - Calmodulin activity regulates group I metabotropic glutamate receptor-mediated signal transduction and synaptic depression. AB - Group I metabotropic glutamate receptors (mGluR), including mGluR1 and mGluR 5 (mGluR1/5), are coupled to Gq and modulate activity-dependent synaptic plasticity. Direct activation of mGluR1/5 causes protein translation-dependent long-term depression (LTD). Although it has been established that intracellular Ca(2+) and the Gq-regulated signaling molecules are required for mGluR1/5 LTD, whether and how Ca(2+) regulates Gq signaling and upregulation of protein expression remain unknown. Through pharmacological inhibition, we tested the function of the Ca(2+) sensor calmodulin (CaM) in intracellular signaling triggered by the activation of mGluR1/5. CaM inhibitor N-[4-aminobutyl]-5-chloro 2-naphthalenesulfonamide hydrochloride (W13) suppressed the mGluR1/5-stimulated activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p70-S6 kinase 1 (S6K1) in hippocampal neurons. W13 also blocked the mGluR1/5 agonist induced synaptic depression in hippocampal slices and in anesthetized mice. Consistent with the function of CaM, inhibiting the downstream targets Ca(2+) /CaM-dependent protein kinases (CaMK) blocked ERK1/2 and S6K1 activation. Furthermore, disruption of the CaM-CaMK-ERK1/2 signaling cascade suppressed the mGluR1/5-stimulated upregulation of Arc expression. Altogether, our data suggest CaM as a new Gq signaling component for coupling Ca(2+) and protein upregulation and regulating mGluR1/5-mediated synaptic modification. PMID- 26864657 TI - Expression of cytokine and apoptosis-related genes in bovine peripheral blood mononuclear cells stimulated with Brucella abortus recombinant proteins. AB - Brucellosis is a clinically and economically important disease. Therefore, eradication programs of the disease have been implemented in several countries. One hurdle in these programs is the detection of infected animals at the early stage. Although the protein antigens as diagnostic antigens have recently received attention, the exact mechanisms at the beginning of immune responses are not yet known. Therefore, genes encoding five B. abortus cellular proteins were cloned and the expressed recombinant proteins were purified. The expression of several cytokine genes (IL-1beta, IL-4, IL-6, IL-12p40, IFN-gamma, TNF-alpha, and iNOS) was analyzed in bovine peripheral blood mononuclear cells (bPBMC) after stimulation with the recombinant proteins. Three apoptosis-related genes, Bax, Bcl-2, and TLR4, were also included in the analysis to find out the adverse effects of the proteins to the cells. Each protein induced different patterns of cytokine expression depending on the stimulation time and antigen dose. Expression of IL-6, IL-12p40, and IFN-gamma was induced with all of the proteins while IL-1beta, IL-4, TNF-alpha, and iNOS gene expression was not. Expression of apoptosis-related genes was not altered except TLR4. These results suggest that the cellular antigens of B. abortus induce both humoral and cellular immunity via the production of IL-6, IL-12p40, and IFN-gamma in bPBMC without exerting any adverse effects on the cells. PMID- 26864658 TI - Research to Publication e-learning. PMID- 26864659 TI - Does Lean healthcare improve patient satisfaction? A mixed-method investigation into primary care. AB - BACKGROUND: Lean healthcare is claimed to contribute to improved patient satisfaction, but there is limited evidence to support this notion. This study investigates how primary-care centres working with Lean define and improve value from the patient's perspective, and how the application of Lean healthcare influences patient satisfaction. METHODS: This paper contains two qualitative case studies and a quantitative study based on results from the Swedish National Patient Survey. Through the case studies, we investigated how primary-care organisations realised the principle of defining and improving value from the patient's perspective. In the quantitative study, we compared results from the patient satisfaction survey for 23 primary-care centres working with Lean with a control group of 23 care centres not working with Lean. We also analysed changes in patient satisfaction over time. RESULTS: Our case studies reveal that Lean healthcare implementations primarily target efficiency and little attention is paid to the patient's perspective. The quantitative study shows no significantly better results in patient satisfaction for primary-care centres working with Lean healthcare compared with those not working with Lean. Further, care centres working with Lean show no significant improvements in patient satisfaction over time. CONCLUSIONS: Lean healthcare implementations seem to have a limited impact on improving patient satisfaction. Care providers need to pay more attention to integrating the patient's perspective in the application of Lean healthcare. Value needs to be defined and value streams need to be improved based on both the knowledge and clinical expertise of care providers, and the preferences and needs of patients. PMID- 26864661 TI - Tolerogenic responses of CD206+, CD83+, FOXP3+, and CTLA-4 to sericin/polyvinyl alcohol/glycerin scaffolds relevant to IL-33 and HSP60 activity. AB - Silk sericin-releasing (sericin/polyvinyl alcohol (PVA)/glycerin) scaffolds have been designed for wound dressing applications using different fabrication techniques that influence scaffold antigenicity. The immunological tolerance of scaffolds depends on the balance of immunogenic and tolerogenic responses modulated by dendritic cells (DCs). An in vivo skin implantation model was used to compare the tolerogenic effect of sericin/PVA/glycerin scaffolds prepared by freeze-drying versus salt-leaching techniques, using an Allevyn(r) scaffold as a control. Immunohistochemical and histopathological studies were performed to evaluate tolerogenic DCs (CD206+), immunogenic DCs (CD83+), regulatory T-cells (FOXP3+ and CTLA-4), a proinflammatory cytokine (interleukin 33: IL-33), a stress marker (heat shock protein 60; HSP60), histopathological changes and related inflammatory cells. It was found that both sericin/PVA/glycerin scaffolds were tolerogenic and induced early activated Treg functions, while the Allevyn(r) scaffold was immunogenic. However, the tolerance of the freeze-dried sericin/PVA/glycerin scaffolds was not as consistent as the salt-leached sericin/PVA/glycerin scaffolds, indicated by the low level of CTLA-4 expression. This was probably due to molecular cross-linking and the morphological and mechanical properties of the freeze-drying technique, which would enhance the immune response. Severe inflammatory responses (including mast cell degranulation and foreign body giant cell accumulation) and histopathological changes (including fat infiltration and fibrosis formation) were mainly found with the Allevyn(r) scaffold, presumably from its architecture and chemical composition, especially polyurethane. The up-regulation of IL-33 and HSP60 with the Allevyn(r) scaffold was correlated with the inflammatory and pathological levels. Our findings suggested that salt-leached sericin/PVA/glycerin scaffolds were tolerogenic, induced a low inflammatory response and were appropriate for wound dressing applications. PMID- 26864660 TI - How to Define the Latent Reservoir: Tools of the Trade. AB - HIV is a devastating worldwide epidemic that has had substantial social and economic impacts throughout the globe. Due to the presence of a small pool of latently infected cells that persists during antiretroviral therapy (ART), HIV is not curable. Because of the high cost of ART and the lack of reliable accessibility across the globe, life-long ART is unfortunately not a feasible solution for the epidemic. Therefore, new strategies need to be developed and implemented to address HIV-1 infection. Several approaches toward this end are currently under investigation (Ebina et al. in Sci Rep 3:2510, 2013; Archin et al. in Nature 487:482-5, 2012; Elliott et al. in PLoS Pathog 10:e1004473, 2014; Rasmussen et al. in Lancet HIV 1:e13-e21, 2014; Tebas et al. in N Engl J Med 370:901-10, 2014; Archin et al. in Nat Rev Microbiol 12:750-64, 2014; Barton et al. in PLoS One 9:e102684, 2014; Sogaard et al. in PLoS Pathog 11:e1005142, 2015). Initial studies have proven promising, but have highlighted the need for sensitive and accurate assays to detect changes in very low concentrations of virus to allow confident interpretation of the success of curative approaches. This review will focus on assays that are currently available and the advantages and limitations of each. PMID- 26864662 TI - On prenatal diagnosis and the decision to continue or terminate a pregnancy in France: a clinical ethics study of unknown moral territories. AB - This article presents a part of the results of an empirical study conducted at a Parisian hospital between 2011 and 2014. It aimed at understanding the women and couples' motivations to terminate or not a pregnancy once a prenatal diagnosis has revealed a genetically related disease in the embryo or fetus. The article first presents the social and legal context of the study, the methodology used and the pathologies that were encountered. Then, it examines the results of the interviews conducted with 5 women alone and 23 couples explaining their reasons for deciding to terminate or not the pregnancy. Finally, it explores the patients' views about the doctor's involvement in the decision-making process. The findings reveal the reasons they formulate when they ponder whether to terminate or not the pregnancy. It highlights the process of their deliberation, their hierarchisation of arguments and concerns. They also show how patients, though often consumed in sorrow, claim to be the legitimate decision-makers, especially women, in a social and legal context in which the rejection of eugenics is viewed as an undisputable principle. PMID- 26864663 TI - Influence of delayed cholecystectomy after acute gallstone pancreatitis on recurrence. Consequences of lack of resources. AB - INTRODUCTION: Acute pancreatitis is often a relapsing condition, particularly when its triggering factor persists. Our goal is to determine the recurrence rate of acute biliary pancreatitis after an initial episode, and the time to relapse, as well as to identify the risk factors for recurrence. MATERIAL AND METHOD: We included all patients admitted for a first acute gallstone pancreatitis event during four years. Primary endpoints included readmission for recurrence and time to relapse. RESULTS: We included 296 patients admitted on a total of 386 occasions. The incidence of acute biliary pancreatitis in our setting is 17.5/100,000 population/year. In all, 19.6% of pancreatitis were severe (22.6% of severe acute pancreatitis for first episodes versus 3.6% for recurring pancreatitis), with an overall mortality of 4.4%. Overall recurrence rate was 15.5%, with a median time to relapse of 82 days. In total, 14.2% of patients relapsed after an acute pancreatitis event without cholecystectomy or endoscopic retrograde cholangio-pancreatography. Severe acute pancreatitis recur in 7.2% of patients, whereas mild cases do so in 16.3%, this being the only risk factor for recurrence thus far identified. CONCLUSIONS: Patients admitted for pancreatitis should undergo cholecystectomy as soon as possible or be guaranteed priority on the waiting list. Otherwise, endoscopic retrograde cholangio-pancreatography with sphincterotomy may be an alternative to surgery for selected patients. PMID- 26864664 TI - Stress urinary incontinence is highly prevalent in recreationally active women attending gyms or exercise classes. AB - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to determine the prevalence of stress urinary incontinence (SUI) in recreationally active women attending gyms or exercise classes. METHODS: Data were collected on the frequency and severity of incontinence and the prevalence of SUI risk factors; screening for PFM dysfunction in a fitness appraisal; symptom modification strategies; knowledge of pelvic floor muscle (PFM) exercises and the Pelvic Floor First (PFF) initiative. Three hundred and sixty-one women aged 18-83 who attended exercise classes or gyms in Western Australia were surveyed. RESULTS: Nearly half (49.3 %) of participants reported SUI, the majority of whom slight or moderate leakage. Ninety-six per cent reported at least one SUI risk factor, with the mean being 2.7 (SD = 1.4). Almost all women surveyed had heard of PFM exercises (97.2 %), but only 15.2 % of participants were screened for PFM dysfunction in a fitness appraisal. Forty-three per cent reported that a fitness instructor cued PFM activation during a workout. Less than 1 in 10 (9.7 %) of the women surveyed had heard about the PFF initiative. CONCLUSION: Urinary incontinence is common in women attending gyms or exercise classes, but is rarely screened for. More education is required to encourage fitness leaders to screen exercise participants and to provide PFM-'friendly" modifications. PMID- 26864666 TI - Evaluation of the local carcinogenic potential of mesh used in the treatment of female stress urinary incontinence. AB - INTRODUCTION AND HYPOTHESIS: To evaluate the carcinogenic potential of implanted synthetic mesh midurethral slings in the treatment of female stress urinary incontinence. METHODS: We identified female patients undergoing implantation of mesh materials for stress urinary incontinence at our institution from 1 January 2002 to 31 December 2012. This was accomplished by querying the medical records for CPT code 57288 ("sling operation for stress incontinence") and a subsequent chart review to identify patients who underwent synthetic mesh sling placement. Medical records were then evaluated for the documentation of bladder, urethral, vaginal, cervical, uterine or ovarian cancers via the International Classification of Disease (ninth edition) coding. A chart review of patients with a cancer diagnosis was performed for verification of the diagnosis and evaluation of the temporal relationship with sling placement. RESULTS: During the study period, 2,474 patients underwent polypropylene midurethral sling placement. The median age was 57 years (IQR 47, 69) and the median follow-up was 60 months (IQR 23.3, 94.9). Overall, 51 patients also had a cancer diagnosis (8 bladder cancers, 7 vaginal malignancies, 8 ovarian carcinomas, 26 endometrial cancers, 2 cervical malignancies); however, only 2 cancers (0.08 %, 2 out of 2,474) developed following sling placement (a vaginal melanoma 3 years after sling placement and an ovarian tumor 1 year after sling placement). No cases of sarcoma formation, bladder, urethral or squamous cell carcinomas were identified. CONCLUSIONS: With a median follow-up of 5 years after synthetic midurethral sling placement, development of pelvic malignancy was rare (0.08 %) and unlikely to be secondary to foreign body reaction from the implanted material. PMID- 26864665 TI - Endopelvic free anchor minisling technique for stress urinary incontinence treatment: 10 years of experience. AB - INTRODUCTION AND HYPOTHESIS: We present our 10-year experience in treating stress urinary incontinence (SUI) using a new minisling technique based on a tension free vaginal tape band designed by our group. The major advantage of this tape is the use of minibelt polypropylene inserted through a single retropubic incision without the use of needles-the Endopelvic Free Anchor (EFA)-based on its location at the midurethra with a U shape. For insertion, each branch is placed using a simple Pean clamp from the vagina with perforation of the endopelvic fascia to achieve a retropubic insertion. METHODS: From May 2001 to May 2011, we surgically treated 166 women with primary first- or second-degree SUI due to urethral hypermobility without genital prolapse. All were evaluated according to our study protocol, which included clinical and urodynamic evaluation before and 12 months after surgery. RESULTS: With a median follow-up of 5 (1-11) years, 152 patients (91.6 %) were fully cured both from urodynamic and subjective points of view. Six patients (3.6 %) had significant improvement, and eight (4.8 %) were identified as technique failure. Complications included one bladder perforation (0.6 %), two cases of postoperative urinary retention (1.24 %), two of retropubic hematoma (1.24 %), and one of de novo urgency (0.6 %). No reinterventions were necessary, and there were no major bleeding complications, no chronic pain or de novo dyspareunia, and no voiding difficulty. CONCLUSIONS: EFA is a viable, safe, and effective technique for treating UI due to urethral hypermobility. PMID- 26864667 TI - Spontaneous coronary artery dissection and its association with heritable connective tissue disorders. AB - OBJECTIVE: Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. METHODS: We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. RESULTS: Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. CONCLUSIONS: Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. PMID- 26864668 TI - Coronary anatomy as related to bicuspid aortic valve morphology. AB - OBJECTIVE: Variable coronary anatomy has been described in patients with bicuspid aortic valves (BAVs). This was never specified to BAV morphology, and prognostic relevance of coronary vessel dominance in this patient group is unclear. The purpose of this study was to evaluate valve morphology in relation to coronary artery anatomy and outcome in patients with isolated BAV and with associated aortic coarctation (CoA). METHODS: Coronary anatomy was evaluated in 186 patients with BAV (141 men (79%), 51+/-14 years) by CT and invasive coronary angiography. Correlation of coronary anatomy was made with BAV morphology and coronary events. RESULTS: Strictly bicuspid valves (without raphe) with left-right cusp fusion (type 1B) had more left dominant coronary systems compared with BAVs with left right cusp fusion with a raphe (type 1A) (48% vs. 26%, p=0.047) and showed more separate ostia (28% vs. 9%, p=0.016). Type 1B BAVs had more coronary artery disease than patients with type 1A BAV (36% vs. 19%, p=0.047). More left dominance was seen in BAV patients with CoA than in patients without (65% vs. 24%, p<0.05). CONCLUSIONS: The incidence of a left dominant coronary artery system and separate ostia was significantly related to BAVs with left-right fusion without a raphe (type 1B). These patients more often had significant coronary artery disease. In patients with BAV and CoA, left dominancy is more common. PMID- 26864670 TI - Inflammatory biomarkers in atrial fibrillation: are they linked to future outcomes? PMID- 26864669 TI - A new electronic screening tool for identifying risk of familial hypercholesterolaemia in general practice. AB - OBJECTIVE: To evaluate the performance of a new electronic screening tool (TARB Ex) in detecting general practice patients at potential risk of familial hypercholesterolaemia (FH). METHODS: Medical records for all active patients seen between 2012 and 2014 (n=3708) at a large general practice in Perth, Western Australia were retrospectively screened for potential FH risk using TARB-Ex. Electronic extracts of medical records for patients identified with potential FH risk (defined as Dutch Lipid Clinic Network Criteria (DLCNC) score >=5) through TARB-Ex were reviewed by a general practitioner (GP) and lipid specialist. High risk patients were recalled for clinical assessment to determine phenotypic FH diagnosis. Performance was evaluated against a manual record review by a GP in the subset of 360 patients with high blood cholesterol (cholesterol >=7 mmol/L or low-density lipoprotein cholesterol >=4.0 mmol/L). RESULTS: Thirty-two patients with DLCNC score >=5 were identified through electronic screening compared with 22 through GP manual review. Sensitivity was 95.5% (95% CI 77.2% to 99.9%), specificity was 96.7% (95% CI 94.3% to 98.3%), negative predictive accuracy was 99.7% (95% CI 98.3% to 100%) and positive predictive accuracy was 65.6% (95% CI 46.9% to 8%). Electronic screening was completed in 10 min compared with 60 h for GP manual review. 10 of 32 patients (31%) were considered high risk and recalled for clinical assessment. Six of seven patients (86%) who attended clinical assessment were diagnosed with phenotypic FH on examination. CONCLUSIONS: TARB-Ex screening is a time-effective and cost-effective method of systematically identifying potential FH risk patients from general practice records for clinical follow-up. PMID- 26864671 TI - Renin-angiotensin system inhibitors in patients with myocardial infarction and secondary mitral regurgitation. AB - OBJECTIVES: Secondary mitral regurgitation (MR) is negatively related to the prognosis of patients with myocardial infarction (MI). Renin-angiotensin system inhibitors (RASI) may favourably affect left ventricular remodelling and reduce afterload and thereby improve prognosis of secondary MR. The aim of this study was to investigate if use of RASI improves prognosis of patients with MI with secondary MR. METHODS: A total of 953 patients with MI were enrolled in this study. Long-term prognosis was compared between patients with MI with no/mild MR (n=657), moderate MR (n=196) and severe MR (n=100). Patients with MI with significant (>=moderate) secondary MR were further divided into those treated with and without RASI. Survival and cardiac-event (all-cause death and congestive heart failure)-free survival were compared. RESULTS: Long-term survival was significantly associated with severity of MR (log-rank, p<0.0001). In patients with significant MR (n=296), RASI was used in 130 patients (44%) and not used in 166 patients (56%). Ejection fraction (47.3+/-12.2 vs 46.6+/-13.4%, p=NS) and E/e' (18.4+/-8.1 vs 16.5+/-7.0, p=NS) were similar between the two groups. Kaplan Meier curves for cardiac-event-free survival demonstrated that use of RASI was associated with better survival (p=0.006) as well as event-free survival (p=0.02). By univariable and multivariable Cox proportional hazard analysis, age (HR 1.046, 95% CI 1.002 to 1.091, p=0.039) and RASI (HR 0.480, 95% CI 0.231 to 0.995), p=0.048) were independent predictors of cardiac events. CONCLUSIONS: Secondary MR affects prognosis in patients with MI. Use of RASI may be associated with better long-term prognosis in patients with MI with significant MR. PMID- 26864672 TI - Neighbourhood socioeconomic status and coronary heart disease in individuals between 40 and 50 years. AB - OBJECTIVE: The incidence of myocardial infarction (MI) has decreased in general but not among younger middle-aged adults. We performed a cohort study of the association between neighbourhood socioeconomic status (SES) at the age of 40 and risk of MI before the age of 50 years. METHODS: All individuals in Sweden were included in the year of their 40th birthday, if it occurred between 1998 and 2010. National registers were used to categorise neighbourhood SES into high, middle and low, and to retrieve information on incident MI and coronary heart disease (CHD). Cox regression models, adjusted for marital status, education level, immigrant status and region of residence, provided an estimate of the HRs and 95% CIs for MI or CHD. RESULTS: Out of 587 933 men and 563 719 women, incident MI occurred in 2877 (0.48%) men and 932 (0.17%) women; and CHD occurred in 4400 (0.74%) men and 1756 (0.31%) women during a mean follow-up of 5.5 years. Using individuals living in middle-SES neighbourhoods as referents, living in high-SES neighbourhoods was associated with lower risk of MI in both sexes (HR (95% CI): men: 0.72 (0.64 to 0.82), women: 0.66 (0.53 to 0.81)); living in low SES neighbourhoods was associated with a higher risk of MI (HR (95% CI): men: 1.31 (1.20 to 1.44), women: 1.28 (1.08 to 1.50)). Similar risk estimates for CHD were found. CONCLUSIONS: The results of our study suggest an increased risk of MI and CHD among residents from low-SES neighbourhoods and a lower risk in those from high-SES neighbourhoods compared with residents in middle-SES neighbourhoods. PMID- 26864673 TI - Therapeutic hypothermia in ST elevation myocardial infarction: a systematic review and meta-analysis of randomised control trials. AB - OBJECTIVE: Our objective is to gain a better understanding of the efficacy and safety of therapeutic hypothermia (TH) in patients with acute ST elevation myocardial infarction (STEMI) through an analysis of randomised controlled trials (RCTs). BACKGROUND: Several RCTs have suggested a positive outcome with the use of TH in the prevention of myocardial injury in the setting of an acute STEMI. However, there are currently no clinical trials that have conclusively shown any significant benefit. METHODS: Electronic databases were used to identify RCTs of TH in the patient population with STEMI. The primary efficacy end point was major adverse cardiovascular event (MACE). Secondary efficacy end points included all cause mortality, infarct size, new myocardial infarction and heart failure/pulmonary oedema (HF/PO). All-bleeding, ventricular arrhythmias and bradycardias were recorded as the safety end points. RESULTS: Six RCTs were included in this meta-analysis, enrolling a total of 819 patients. There was no significant benefit from TH in preventing MACE (OR, 01.04; 95% CI 0.37 to 2.89), all-cause mortality (OR, 1.48; 95% CI 0.68 to 3.19), new myocardial infarction (OR, 0.99; 95% CI 0.20 to 4.94), HF/PO (OR, 0.52; 95% CI 0.15 to 1.77) or infarct size (standard difference of the mean (SDM), -0.1; 95% CI -0.23 to 0.04). However, a significant reduction of infarct size was observed with TH utilisation in anterior wall myocardial infarction (SDM, -0.23; 95% CI -0.45 to -0.02). There was no significant difference seen for the safety end points all-bleeding (OR 1.32; 95% CI 0.77 to 2.24), ventricular arrhythmias (OR, 0.85; 95% CI 0.54 to 1.36) or bradycardias (OR, 1.16; 95% CI 0.74 to 1.83). CONCLUSIONS: Although TH appears to be safe in patients with STEMI, meta-analysis of published RCTs indicates that benefit is limited to reduction of infarct size in patients with anterior wall involvement with no demonstrable effect on all-cause mortality, recurrent myocardial infarction or HF/PO. PMID- 26864676 TI - Use of an Electronic Medical Record to Assess Patient-Reported Morbidity Following Ureteroscopy. AB - BACKGROUND AND PURPOSE: With the extensive documentation afforded by our electronic medical record (EMR), we observed an unusually high number of patient initiated encounters following ureteroscopy (URS). We sought to quantify and categorize patient encounters following URS to determine if we could identify avoidable common problems. MATERIALS AND METHODS: Following IRB approval, we reviewed the records of 298 consecutive patients with stones who underwent 314 URS procedures between July 2013 and November 2014. Patient demographics, stone characteristics and operative details, as well as telephone encounters, secure online patient-initiated (MyChart) messages, and emergency department (ED) visits following URS were extracted from our EMR (Epic, Verona, WI). We performed univariate (UVA) and multivariate (MVA) analysis to identify factors predictive of postoperative patient encounters and compared URS patients to a group of 56 patients undergoing transurethral resection of bladder tumor (TURBT) for number and type of encounters. RESULTS: We identified 443 encounters generated by 201 URS patients, including 334 telephone calls, 71 MyChart messages, and 38 ED visits. Among these encounters, 352 (79%) were medically related (pain comprised 45%) and the remainder involved scheduling issues. By UVA age, bilateral versus unilateral URS, stone location (both kidney and ureter), ureteral access sheath size, and total number of stones predicted a postoperative encounter. By MVA, only younger age and larger UAS size were independent predictors. When compared with TURBT patients, URS patients had a 2.5-fold higher risk of having a pain related postoperative encounter (OR 2.54, 95% CI 1.08-7.04, P=0.03). CONCLUSIONS: Among patients undergoing URS for stones, two-thirds made unprompted contact with a healthcare provider and 80% of contacts involved postoperative pain, a finding that is distinct from another endoscopic procedure that does not involve upper tract manipulation. Patients do not perceive URS as the benign procedure doctors do. PMID- 26864677 TI - Cell-based strategies for vascular regeneration. AB - Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ. PMID- 26864674 TI - Using electronic health records to predict costs and outcomes in stable coronary artery disease. AB - OBJECTIVES: To use electronic health records (EHR) to predict lifetime costs and health outcomes of patients with stable coronary artery disease (stable-CAD) stratified by their risk of future cardiovascular events, and to evaluate the cost-effectiveness of treatments targeted at these populations. METHODS: The analysis was based on 94 966 patients with stable-CAD in England between 2001 and 2010, identified in four prospectively collected, linked EHR sources. Markov modelling was used to estimate lifetime costs and quality-adjusted life years (QALYs) stratified by baseline cardiovascular risk. RESULTS: For the lowest risk tenth of patients with stable-CAD, predicted discounted remaining lifetime healthcare costs and QALYs were L62 210 (95% CI L33 724 to L90 043) and 12.0 (95% CI 11.5 to 12.5) years, respectively. For the highest risk tenth of the population, the equivalent costs and QALYs were L35 549 (95% CI L31 679 to L39 615) and 2.9 (95% CI 2.6 to 3.1) years, respectively. A new treatment with a hazard reduction of 20% for myocardial infarction, stroke and cardiovascular disease death and no side-effects would be cost-effective if priced below L72 per year for the lowest risk patients and L646 per year for the highest risk patients. CONCLUSIONS: Existing EHRs may be used to estimate lifetime healthcare costs and outcomes of patients with stable-CAD. The stable-CAD model developed in this study lends itself to informing decisions about commissioning, pricing and reimbursement. At current prices, to be cost-effective some established as well as future stable-CAD treatments may require stratification by patient risk. PMID- 26864678 TI - AC Conduction and Time-Temperature Superposition Scaling in a Reduced Graphene Oxide-Zinc Sulfide Nanocomposite. AB - We report, herein, the results of an in depth study and concomitant analysis of the AC conduction [sigma'(omega): f=20 Hz to 2 MHz] mechanism in a reduced graphene oxide-zinc sulfide (RGO-ZnS) composite. The magnitude of the real part of the complex impedance decreases with increase in both frequency and temperature, whereas the imaginary part shows an asymptotic maximum that shifts to higher frequencies with increasing temperature. On the other hand, the conductivity isotherm reveals a frequency-independent conductivity at lower frequencies subsequent to a dispersive conductivity at higher frequencies, which follows a power law [sigma'(omega)?omega(s) ] within a temperature range of 297 to 393 K. Temperature-independent frequency exponent 's' indicates the occurrence of phonon-assisted simple quantum tunnelling of electrons between the defects present in RGO. Finally, this sample follows the "time-temperature superposition principle", as confirmed from the universal scaling of conductivity isotherms. These outcomes not only pave the way for increasing our elemental understanding of the transport mechanism in the RGO system, but will also motivate the investigation of the transport mechanism in other order-disorder systems. PMID- 26864679 TI - Femtosecond laser for cavity preparation in enamel and dentin: ablation efficiency related factors. AB - To study the effects of laser fluence (laser energy density), scanning line spacing and ablation depth on the efficiency of a femtosecond laser for three dimensional ablation of enamel and dentin. A diode-pumped, thin-disk femtosecond laser (wavelength 1025 nm, pulse width 400 fs) was used for the ablation of enamel and dentin. The laser spot was guided in a series of overlapping parallel lines on enamel and dentin surfaces to form a three-dimensional cavity. The depth and volume of the ablated cavity was then measured under a 3D measurement microscope to determine the ablation efficiency. Different values of fluence, scanning line spacing and ablation depth were used to assess the effects of each variable on ablation efficiency. Ablation efficiencies for enamel and dentin were maximized at different laser fluences and number of scanning lines and decreased with increases in laser fluence or with increases in scanning line spacing beyond spot diameter or with increases in ablation depth. Laser fluence, scanning line spacing and ablation depth all significantly affected femtosecond laser ablation efficiency. Use of a reasonable control for each of these parameters will improve future clinical application. PMID- 26864680 TI - Persistence in eye movement during visual search. AB - As any cognitive task, visual search involves a number of underlying processes that cannot be directly observed and measured. In this way, the movement of the eyes certainly represents the most explicit and closest connection we can get to the inner mechanisms governing this cognitive activity. Here we show that the process of eye movement during visual search, consisting of sequences of fixations intercalated by saccades, exhibits distinctive persistent behaviors. Initially, by focusing on saccadic directions and intersaccadic angles, we disclose that the probability distributions of these measures show a clear preference of participants towards a reading-like mechanism (geometrical persistence), whose features and potential advantages for searching/foraging are discussed. We then perform a Multifractal Detrended Fluctuation Analysis (MF-DFA) over the time series of jump magnitudes in the eye trajectory and find that it exhibits a typical multifractal behavior arising from the sequential combination of saccades and fixations. By inspecting the time series composed of only fixational movements, our results reveal instead a monofractal behavior with a Hurst exponent , which indicates the presence of long-range power-law positive correlations (statistical persistence). We expect that our methodological approach can be adopted as a way to understand persistence and strategy-planning during visual search. PMID- 26864681 TI - Lipophosphoramidate-based bipolar amphiphiles: their syntheses and transfection properties. AB - Six new cationic bolaamphiphiles (also called bipolar amphiphiles, bolaform amphiphiles, or bolalipids) were readily prepared by a thiol-ene click reaction that engaged a mercapto-alcohol (mercapto-ethanol or mercapto-hexanol) and a cationic based lipophosphoramidate. The cationic lipophosphoramidates contain two lipid chains that end in an alkene group and a selected cationic polar head group (trimethylammonium, dimethyl hydroxyethyl ammonium, or methylimidazolium). These compounds were formulated in water (with or without DOPE as a colipid) to produce supramolecular aggregates. These aggregates, before (i.e. bolasomes) and after (i.e. bolaplexes) mixing with plasmid DNA (pDNA) at various charge ratios, were characterized with regard to their sizes and zeta potentials. In the case of bolasomes, the suspensions were unstable since precipitation occurred after only a few hours at room temperature. On the other hand, bolaplex formulations exhibited clearly a better colloidal stability. Then, the gene delivery properties of the cationic bolasomes were investigated using two human-derived epithelial cell lines (A549 and 16HBE). Compared to the commercially available lipofection reagent (Lipofectamine), most of the cationic bolaamphiphiles were able to efficiently transfect these cells when they were formulated with DOPE in a 1 : 1 molar ratio. We report herein that bolaamphiphiles possessing a trimethylammonium or a dimethyl hydroxyethyl ammonium head group were the most efficient in terms of transfection efficiency while exhibiting no significant cytotoxicity. PMID- 26864682 TI - Long-term follow-up ultrasonography after lobectomy in papillary thyroid microcarcinoma patients: A single-center study. AB - PURPOSE: This study aimed to assess the prevalence of tumor recurrence and to determine the appropriate interval of follow-up ultrasonography (US) in papillary thyroid microcarcinoma (PTMC) patients who underwent lobectomy. METHODS: Between January and December 2006, 137 patients underwent a lobectomy for the treatment of PTMC and at least one postoperative US follow-up examination. The postoperative follow-up US was performed by a single radiologist for all patients. Based on the follow-up US and histopathological results, tumor recurrence and nodal metastasis were determined. RESULTS: In the 137 patients, the following diagnoses were made after lobectomy: intraglandular PTMC (n = 104), focally perithyroidal PTMC invasion within surgical margins (n = 18), nodal metastasis to the ipsilateral level VI node (n = 20), and satellite PTMC (n = 7). The patients showed differences in the number of post-operative follow-up US sessions and in the intervals of those sessions. Of the 137 patients, 135 (98.5%) exhibited no tumor recurrence on the follow-up US, whereas 2 (1.5%) exhibited tumor recurrence in the remnant thyroid gland. In these two patients with tumor recurrence, suspicious thyroid nodules were detected at the 96- and 90-month follow-up US, respectively. CONCLUSIONS: In this study, the PTMC tumor recurrence rate was low, indicating that early post-lobectomy follow-up US in short intervals is not beneficial for detecting PTMC recurrence. PMID- 26864684 TI - Corrigendum to "In vivo single-molecule imaging of bacterial DNA replication, transcription, and repair" [FEBS Lett. 588 (19) (2014) 3585-3594]. PMID- 26864686 TI - Two-bit memory and quantized storage phenomenon in conventional MOS structures with double-stacked Pt-NCs in an HfAlO matrix. AB - A two-bit memory and quantized storage phenomenon are observed at room temperature for a device based on the traditional MOS structure with double stacked Pt-nanocrystals (Pt-NCs). A 2.68 and 1.72 V flat band voltage shift (memory window) has been obtained when applying a +/-7 V programming/erasing voltage to the structures with double-stacked Pt-NCs. The memory windows of 2.40 and 1.44 V can be retained after stress for 10(5) seconds, which correspond to 89.55% and 83.72% stored charges reserved. The quantized charge storage phenomenon characterized by current-voltage (J-V) hysteresis curves was detected at room temperature. The shrinkage of the memory window results from the decreasing tunneling probability, which strongly depends on the number of stacks. The traps, de-traps and quantum confinement effects of Pt-NCs may contribute to the improvement of dielectric characteristics and the two-bit memory behavior. The multi-bit memory and quantized storage behavior observed in the Pt-NCs stacks structure at room temperature might provide a feasible method for realizing the multi-bit storage in non-volatile flash memory devices. PMID- 26864683 TI - The repair Schwann cell and its function in regenerating nerves. AB - Nerve injury triggers the conversion of myelin and non-myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de-differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury-induced Schwann cell reprogramming involves down-regulation of myelin genes combined with activation of a set of repair-supportive features, including up-regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c Jun, which is rapidly up-regulated in Schwann cells after injury. In the absence of c-Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c-Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non-myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed. PMID- 26864687 TI - Gene regulatory network inference using fused LASSO on multiple data sets. AB - Devising computational methods to accurately reconstruct gene regulatory networks given gene expression data is key to systems biology applications. Here we propose a method for reconstructing gene regulatory networks by simultaneous consideration of data sets from different perturbation experiments and corresponding controls. The method imposes three biologically meaningful constraints: (1) expression levels of each gene should be explained by the expression levels of a small number of transcription factor coding genes, (2) networks inferred from different data sets should be similar with respect to the type and number of regulatory interactions, and (3) relationships between genes which exhibit similar differential behavior over the considered perturbations should be favored. We demonstrate that these constraints can be transformed in a fused LASSO formulation for the proposed method. The comparative analysis on transcriptomics time-series data from prokaryotic species, Escherichia coli and Mycobacterium tuberculosis, as well as a eukaryotic species, mouse, demonstrated that the proposed method has the advantages of the most recent approaches for regulatory network inference, while obtaining better performance and assigning higher scores to the true regulatory links. The study indicates that the combination of sparse regression techniques with other biologically meaningful constraints is a promising framework for gene regulatory network reconstructions. PMID- 26864688 TI - Academic Achievement of Deaf and Hard-of-Hearing Students in an ASL/English Bilingual Program. AB - There has been a scarcity of studies exploring the influence of students' American Sign Language (ASL) proficiency on their academic achievement in ASL/English bilingual programs. The aim of this study was to determine the effects of ASL proficiency on reading comprehension skills and academic achievement of 85 deaf or hard-of-hearing signing students. Two subgroups, differing in ASL proficiency, were compared on the Northwest Evaluation Association Measures of Academic Progress and the reading comprehension subtest of the Stanford Achievement Test, 10th edition. Findings suggested that students highly proficient in ASL outperformed their less proficient peers in nationally standardized measures of reading comprehension, English language use, and mathematics. Moreover, a regression model consisting of 5 predictors including variables regarding education, hearing devices, and secondary disabilities as well as ASL proficiency and home language showed that ASL proficiency was the single variable significantly predicting results on all outcome measures. This study calls for a paradigm shift in thinking about deaf education by focusing on characteristics shared among successful deaf signing readers, specifically ASL fluency. PMID- 26864689 TI - Longitudinal Receptive American Sign Language Skills Across a Diverse Deaf Student Body. AB - This article presents results of a longitudinal study of receptive American Sign Language (ASL) skills for a large portion of the student body at a residential school for the deaf across four consecutive years. Scores were analyzed by age, gender, parental hearing status, years attending the residential school, and presence of a disability (i.e., deaf with a disability). Years 1 through 4 included the ASL Receptive Skills Test (ASL-RST); Years 2 through 4 also included the Receptive Test of ASL (RT-ASL). Student performance for both measures positively correlated with age; deaf students with deaf parents scored higher than their same-age peers with hearing parents in some instances but not others; and those with a documented disability tended to score lower than their peers without disabilities. These results provide longitudinal findings across a diverse segment of the deaf/hard of hearing residential school population. PMID- 26864690 TI - Assessing and Mapping the Availability of the Female Condom in the Philadelphia Metropolitan Area. AB - This study assessed and mapped the availability of the female condom in relation to the male condom and HIV prevalence in the Philadelphia metropolitan area, which has a high density of HIV. One percent of the 1228 service providers contacted sold/provided the female condom and 77 % sold/provided the male condom. The lack of availability of the female condom suggests this product will have no public health impact on reducing HIV and that interventions that promote use of the female condom are not sustainable in this high-risk area. Our findings may help policy makers increase female condom availability in this area. PMID- 26864691 TI - A Systematic Review of Health Literacy Interventions for People Living with HIV. AB - Health literacy significantly impacts health-related outcomes among people living with HIV. Our aim was to systematically review current literature on health literacy interventions for people living with HIV. The authors conducted a thorough literature search following the PRISMA statement and the AMSTAR checklist as a guide, and found six studies that met inclusion/exclusion criteria. The majority of these interventions were designed to improve HIV treatment adherence as well as HIV knowledge and treatment-related skills, with one study focusing on e-Health literacy. Several of the studies demonstrated trends toward improvement in medication adherence, but most did not achieve statistical significance primarily due to methodological limitations. Significant improvements in knowledge, behavioral skills, and e-Health literacy were found following interventions (p = 0.001-0.05). Health literacy interventions have the potential to promote HIV-related knowledge, behavioral skills, and self management practices. More research is needed to assess the efficacy of interventions to promote a variety of self-management practices. PMID- 26864693 TI - Downregulation of miR-384-5p attenuates rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through inhibiting endoplasmic reticulum stress. AB - Endoplasmic reticulum (ER) stress has been linked to the pathogenesis of Parkinson's disease (PD). However, the role of microRNAs (miRNAs) in this process involved in PD remains poorly understood. Recent studies indicate that miR-384-5p plays an important role for cell survival in response to different insults, but the role of miR-384-5p in PD-associated neurotoxicity remains unknown. In this study, we investigated the role of miR-384-5p in an in vitro model of PD using dopaminergic SH-SY5Y cells treated with rotenone. We found that miR-384-5p was persistently induced by rotenone in neurons. Also, the inhibition of miR-384-5p significantly suppressed rotenone-induced neurotoxicity, while overexpression of miR-384-5p aggravated rotenone-induced neurotoxicity. Through bioinformatics and dual-luciferase reporter assay, miR-384-5p was found to directly target the 3' untranslated region of glucose-regulated protein 78 (GRP78), the master regulator of ER stress sensors. Quantitative polymerase chain reaction and Western blotting analysis showed that miR-384-5p negatively regulated the expression of GRP78. Inhibition of miR-384-5p remarkably suppressed rotenone-evoked ER stress, which was evident by a reduction in the phosphorylation of activating transcription factor 4 (ATF4) and inositol-requiring enzyme 1 (IRE1alpha). The downstream target genes of ER stress including CCAAT/enhancer-binding protein-homologous protein (CHOP) and X box-binding protein-1 (XBP-1) were also decreased by the miR 384-5p inhibitor. In contrast, overexpression of miR-384-5p enhanced ER stress signaling. In addition, knockdown of GRP78 significantly abrogated the inhibitory effect of miR-384-5p inhibitors on cell apoptosis and ER stress signaling. Moreover, we observed a significant increase of miR-384-5p expression in primary neurons induced by rotenone. Taken together, our results suggest that miR-384-5p mediated ER stress by negatively regulating GRP78 and that miR-384-5p inhibition might be a novel and promising approach for the treatment of PD. PMID- 26864692 TI - Interpersonal Mechanisms Contributing to the Association Between HIV-Related Internalized Stigma and Medication Adherence. AB - Previous research suggests that people living with HIV (PLWH) sometimes internalize HIV-related stigma existing in the community and experience feelings of inferiority and shame due to their HIV status, which can have negative consequences for treatment adherence. PLWH's interpersonal concerns about how their HIV status may affect the security of their existing relationships may help explain how internalized stigma affects adherence behaviors. In a cross-sectional study conducted between March 2013 and January 2015 in Birmingham, AL, 180 PLWH recruited from an outpatient HIV clinic completed previously validated measures of internalized stigma, attachment styles, and concern about being seen while taking HIV medication. Participants also self-reported their HIV medication adherence. Higher levels of HIV-related internalized stigma, attachment-related anxiety (i.e., fear of abandonment by relationship partners), and concerns about being seen by others while taking HIV medication were all associated with worse medication adherence. The effect of HIV-related internalized stigma on medication adherence was mediated by attachment-related anxiety and by concerns about being seen by others while taking HIV medication. Given that medication adherence is vitally important for PLWH to achieve long-term positive health outcomes, understanding interpersonal factors affecting medication adherence is crucial. Interventions aimed at improving HIV treatment adherence should address interpersonal factors as well as intrapersonal factors. PMID- 26864694 TI - Analysis of phosphorylation of the myosin-targeting subunit of myosin light chain phosphatase by Phos-tag SDS-PAGE. AB - Phosphorylation of the myosin-targeting subunit 1 of myosin light chain phosphatase (MYPT1) plays an important role in the regulation of smooth muscle contraction, and several sites of phosphorylation by different protein Ser/Thr kinases have been identified. Furthermore, in some instances, phosphorylation at specific sites affects phosphorylation at neighboring sites, with functional consequences. Characterization of the complex phosphorylation of MYPT1 in tissue samples at rest and in response to contractile and relaxant stimuli is, therefore, challenging. We have exploited Phos-tag SDS-PAGE in combination with Western blotting using antibodies to MYPT1, including phosphospecific antibodies, to separate multiple phosphorylated MYPT1 species and quantify MYPT1 phosphorylation stoichiometry using purified, full-length recombinant MYPT1 phosphorylated by Rho-associated coiled-coil kinase (ROCK) and cAMP-dependent protein kinase (PKA). This approach confirmed that phosphorylation of MYPT1 by ROCK occurs at Thr(697)and Thr(855), PKA phosphorylates these two sites and the neighboring Ser(696)and Ser(854), and prior phosphorylation at Thr(697)and Thr(855)by ROCK precludes phosphorylation at Ser(696)and Ser(854)by PKA. Furthermore, phosphorylation at Thr(697)and Thr(855)by ROCK exposes two other sites of phosphorylation by PKA. Treatment of Triton-skinned rat caudal arterial smooth muscle strips with the membrane-impermeant phosphatase inhibitor microcystin or treatment of intact tissue with the membrane-permeant phosphatase inhibitor calyculin A induced slow, sustained contractions that correlated with phosphorylation of MYPT1 at 7 to >=10 sites. Phos-tag SDS-PAGE thus provides a suitable and convenient method for analysis of the complex, multisite MYPT1 phosphorylation events involved in the regulation of myosin light chain phosphatase activity and smooth muscle contraction. PMID- 26864695 TI - Comparison of the Glasgow Prognostic Score (GPS) and the modified Glasgow Prognostic Score (mGPS) in evaluating the prognosis of patients with operable and inoperable non-small cell lung cancer. AB - PURPOSE: The Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) are shown to be reliable prognostic indexes in patients with operable and inoperable non-small cell lung cancer (NSCLC). Considering the difference between the two indexes lies in whether hypoalbuminemia without an elevated C-reactive protein (CRP) is associated with worse survival, this study aims to evaluate the prognostic performance of hypoalbuminemia in patients without an elevated CRP and to compare the prognostic value of GPS and mGPS in patients with operable and inoperable NSCLC. METHODS: The data of 2988 patients were retrospectively collected from the Shanghai Health Information Network. Univariate and multivariate Cox regression was performed to investigate the prognostic effect of albumin, CRP, GPS and mGPS. Restricted cubic spline was also performed to evaluate the relationship between albumin and hazard ratio. Kaplan-Meier survival curves were estimated and compared using the log-rank test. Additional discriminative ability of GPS and of mGPS was evaluated using the area under the curve and Harrell's concordance index. RESULTS: Hypoalbuminemia was associated with worse survival in both operable and inoperable patients without an elevated CRP. The Kaplan-Meier survival curve of hypoalbuminemic patients without an elevated CRP was more close to the curve of patients with an elevated CRP and a normal albumin than to the curve of patients with neither of these abnormalities. Multivariate analysis, AUC and C-index all indicated that GPS had a higher prognostic value than mGPS. CONCLUSIONS: Hypoalbuminemia was associated with worse survival in patients with or without an elevated CRP. GPS was superior to mGPS in predicting survival in operable and inoperable NSCLC patients. PMID- 26864697 TI - Conservation of the freshwater fauna of Patagonia: an alert to the urgent need for integrative management and sustainable development. PMID- 26864696 TI - Controlled release of a heterogeneous human placental matrix from PLGA microparticles to modulate angiogenesis. AB - A significant hurdle limiting musculoskeletal tissue regeneration is the inability to develop effective vascular networks to support cellular development within engineered constructs. Due to the inherent complexity of angiogenesis, where multiple biochemical pathways induce and control vessel formation, our laboratory has taken an alternate approach using a matrix material containing angiogenic and osteogenic proteins derived from human placental tissues. Single bolus administrations of the human placental matrix (hPM) have been shown to initiate angiogenesis but vascular networks deteriorated over time. Controlled/sustained delivery was therefore hypothesized to stabilize and extend network formation. To test this hypothesis, hPM was encapsulated in degradable poly(lactic-co-glycolic acid) (PLGA) microparticles to extend the release period. Microparticle preparation including loading, size, encapsulation efficiency, and release profile was optimized for hPM. The angiogenic cellular response to the hPM/PLGA-loaded microparticles was assessed in 3D alginate hydrogel matrices seeded with primary human endothelial cells. Results show an average microparticle diameter of 91.82 +/- 2.92 MUm, with an encapsulation efficiency of 75%, and a release profile extending over 30 days. Three-dimensional angiogenic assays with hPM-loaded PLGA microparticles showed initial stimulation of angiogenic tubules after 14 days and further defined network formations after 21 days of culture. Although additional optimization is necessary, these studies confirm the effectiveness of a novel controlled multi-protein release approach to induce and maintain capillary networks within alginate tissue scaffolds. PMID- 26864698 TI - Visualization of cerebrospinal fluid flow in syringomyelia through noninvasive magnetic resonance imaging with a time-spatial labeling inversion pulse (Time SLIP). AB - CONTEXT: We report a case of syringomyelia assessed by magnetic resonance imaging (MRI) with a time-spatial labeling inversion pulse (Time-SLIP), which is a non contrast MRI technique that uses the cerebrospinal fluid (CSF) as an intrinsic tracer, thus removing the need to administer a contrast agent. Time-SLIP permits investigation of flow movement for over 3 seconds without any limitations associated with the cardiac phase, and it is a clinically accessible method for flow analysis. FINDINGS: We investigated an 85-year-old male experiencing progressive gait disturbance, with leg numbness and muscle weakness. Conventional MRI revealed syringomyelia from C7 to T12, with multiple webs of cavities. We then applied the Time-SLIP approach to characterize CSF flow in the syringomyelic cavities. Time-SLIP detected several unique CSF flow patterns that could not be observed by conventional imaging. The basic CSF flow pattern in the subarachnoid space was pulsatile and was harmonious with the heartbeat. Several unique flow patterns, such as bubbles, jumping, and fast flow, were observed within syringomyelic cavities by Time-SLIP imaging. These patterns likely reflect the complex flow paths through the septum and/or webs of cavities. CONCLUSION/CLINICAL RELEVANCE: Time-SLIP permits observation of CSF motion over a long period of time and detects patterns of flow velocity and direction. Thus, this novel approach to CSF flow analysis can be used to gain a more extensive understanding of spinal disease pathology and to optimize surgical access in the treatment of spinal lesions. Additionally, Time-SLIP has broad applicability in the field of spinal research. PMID- 26864700 TI - Thromboelastometry profiles in patients undergoing thrombolytic therapy for acute ischaemic stroke. PMID- 26864699 TI - Electroextraction and electromembrane extraction: Advances in hyphenation to analytical techniques. AB - Electroextraction (EE) and electromembrane extraction (EME) are sample preparation techniques that both require an electric field that is applied over a liquid-liquid system, which enables the migration of charged analytes. Furthermore, both techniques are often used to pre-concentrate analytes prior to analysis. In this review an overview is provided of the body of literature spanning April 2012-November 2015 concerning EE and EME, focused on hyphenation to analytical techniques. First, the theoretical aspects of concentration enhancement in EE and EME are discussed to explain extraction recovery and enrichment factor. Next, overviews are provided of the techniques based on their hyphenation to LC, GC, CE, and direct detection. These overviews cover the compounds and matrices, experimental aspects (i.e. donor volume, acceptor volume, extraction time, extraction voltage, and separation time) and the analytical aspects (i.e. limit of detection, enrichment factor, and extraction recovery). Techniques that were either hyphenated online to analytical techniques or show high potential with respect to online hyphenation are highlighted. Finally, the potential future directions of EE and EME are discussed. PMID- 26864701 TI - Electrospun Nanofibers from a Tricyanofuran-Based Molecular Switch for Colorimetric Recognition of Ammonia Gas. AB - A chromophore based on tricyanofuran (TCF) with a hydrazone (H) recognition moiety was developed. Its molecular-switching performance is reversible and has differential sensitivity towards aqueous ammonia at comparable concentrations. Nanofibers were fabricated from the TCF-H chromophore by electrospinning. The film fabricated from these nanofibers functions as a solid-state optical chemosensor for probing ammonia vapor. Recognition of ammonia vapor occurs by proton transfer from the hydrazone fragment of the chromophore to the ammonia nitrogen atom and is facilitated by the strongly electron withdrawing TCF fragment. The TCF-H chromophore was added to a solution of poly(acrylic acid), which was electrospun to obtain a nanofibrous sensor device. The morphology of the nanofibrous sensor was determined by SEM, which showed that nanofibers with a diameter range of 200-450 nm formed a nonwoven mat. The resultant nanofibrous sensor showed very good sensitivity in ammonia-vapor detection. Furthermore, very good reversibility and short response time were also observed. PMID- 26864703 TI - Multinary I-III-VI2 and I2-II-IV-VI4 Semiconductor Nanostructures for Photocatalytic Applications. AB - Semiconductor nanostructures that can effectively serve as light-responsive photocatalysts have been of considerable interest over the past decade. This is because their use in light-induced photocatalysis can potentially address some of the most serious environmental and energy-related concerns facing the world today. One important application is photocatalytic hydrogen production from water under solar radiation. It is regarded as a clean and sustainable approach to hydrogen fuel generation because it makes use of renewable resources (i.e., sunlight and water), does not involve fossil fuel consumption, and does not result in environmental pollution or greenhouse gas emission. Another notable application is the photocatalytic degradation of nonbiodegradable dyes, which offers an effective way of ridding industrial wastewater of toxic organic pollutants prior to its release into the environment. Metal oxide semiconductors (e.g., TiO2) are the most widely studied class of semiconductor photocatalysts. Their nanostructured forms have been reported to efficiently generate hydrogen from water and effectively degrade organic dyes under ultraviolet-light irradiation. However, the wide band gap characteristic of most metal oxides precludes absorption of light in the visible region, which makes up a considerable portion of the solar radiation spectrum. Meanwhile, nanostructures of cadmium chalcogenide semiconductors (e.g., CdS), with their relatively narrow band gap that can be easily adjusted through size control and alloying, have displayed immense potential as visible-light-responsive photocatalysts, but the intrinsic toxicity of cadmium poses potential risks to human health and the environment. In developing new nanostructured semiconductors for light-driven photocatalysis, it is important to choose a semiconducting material that has a high absorption coefficient over a wide spectral range and is safe for use in real-world settings. Among the most promising candidates are the multinary chalcogenide semiconductors (MCSs), which include the ternary I-III-VI2 semiconductors (e.g., AgGaS2, CuInS2, and CuInSe2) and the quaternary I2-II-IV VI4 semiconductors (e.g., Cu2ZnGeS4, Cu2ZnSnS4, and Ag2ZnSnS4). These inorganic compounds consist of environmentally benign elemental components, exhibit excellent light-harvesting properties, and possess band gap energies that are well-suited for solar photon absorption. Moreover, the band structures of these materials can be conveniently modified through alloying to boost their ability to harvest visible photons. In this Account, we provide a summary of recent research on the use of ternary I-III-VI2 and quaternary I2-II-IV-VI4 semiconductor nanostructures for light-induced photocatalytic applications, with focus on hydrogen production and organic dye degradation. We include a review of the solution-based methods that have been employed to prepare multinary chalcogenide semiconductor nanostructures of varying compositions, sizes, shapes, and crystal structures, which are factors that are known to have significant influence on the photocatalytic activity of semiconductor photocatalysts. The enhancement of photocatalytic performance through creation of hybrid nanoscale architectures is also presented. Lastly, views on the current challenges and future directions are discussed in the concluding section. PMID- 26864704 TI - Dipping in Ambulatory Blood Pressure Monitoring Correlates With Overnight Urinary Excretion of Catecholamines and Sodium. AB - Nondipping blood pressure (BP) is associated with increased morbidity and mortality. This study examines the relationship of "dipping" in 24-hour ambulatory BP monitoring (ABPM) with awake and sleeping urinary norepinephrine (NE) and epinephrine (EPI), and that of urinary NE and EPI with urinary sodium (UNa). Fifty nondippers and 65 dippers were included in the present study. Collected data included age, sex, body mass index, history of hypertension, current antihypertensive treatment, ABPM data, and NE, EPI, and UNa values. Hierarchical multiple regression analysis with the night-to-day ratio (NDR) of systolic BP as a dependent variable showed that the composite term of the NDRs of urinary NE and EPI was a significant predictor for dipping. Results also show a differential role of NE and EPI in circadian UNa excretion in dippers and nondippers. These results indicate that the sympathetic nervous system is involved in the regulation of circadian BP variations and UNa excretion. PMID- 26864705 TI - Interference of functional monomers with polymerization efficiency of adhesives. AB - The degree of conversion (DC) of camphorquinone/amine-based adhesives is affected by acidic functional monomers as a result of inactivation of the amine co initiator through an acid-base reaction. During bonding, functional monomers of self-etch adhesives chemically interact with hydroxyapatite (HAp). Here, we tested in how far the latter interaction of functional monomers with HAp counteracts the expected reduction in DC of camphorquinone/amine-based adhesives. The DC of three experimental adhesive formulations, containing either of the two functional monomers [10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) or 4 methacryloxyethyl trimellitic acid anhydride (4-META)] or no functional monomer (no-FM; control), was measured with and without HAp powder added to the adhesive formulations. Both the variables 'functional monomer' and 'HAp' were found to be significant, with the functional monomer reducing the DC and HAp counteracting this effect. It is concluded that the functional monomers 10-MDP and 4-META interfere with the polymerization efficiency of adhesives. This interference is less prominent in the presence of HAp, which would clinically correspond to when these two functional monomers of the adhesive simultaneously interact with HAp in tooth tissue. PMID- 26864706 TI - Behavioural response to combined insecticide and temperature stress in natural populations of Drosophila melanogaster. AB - Insecticide resistance evolves extremely rapidly, providing an illuminating model for the study of adaptation. With climate change reshaping species distribution, pest and disease vector control needs rethinking to include the effects of environmental variation and insect stress physiology. Here, we assessed how both long-term adaptation of populations to temperature and immediate temperature variation affect the genetic architecture of DDT insecticide response in Drosophila melanogaster. Mortality assays and behavioural assays based on continuous activity monitoring were used to assess the interaction between DDT and temperature on three field-derived populations from climate extremes (Raleigh for warm temperate, Tasmania for cold oceanic and Queensland for hot tropical). The Raleigh population showed the highest mortality to DDT, whereas the Queensland population, epicentre for derived alleles of the resistance gene Cyp6g1, showed the lowest. Interaction between insecticide and temperature strongly affected mortality, particularly for the Tasmanian population. Activity profiles analysed using self-organizing maps show that the insecticide promoted an early response, whereas elevated temperature promoted a later response. These distinctive early or later activity phases revealed similar responses to temperature and DDT dose alone but with more or less genetic variance depending on the population. This change in genetic variance among populations suggests that selection particularly depleted genetic variance for DDT response in the Queensland population. Finally, despite similar (co)variation between traits in benign conditions, the genetic responses across population differed under stressful conditions. This showed how stress-responsive genetic variation only reveals itself in specific conditions and thereby escapes potential trade-offs in benign environments. PMID- 26864707 TI - Neoadjuvant Chemotherapy Using Reduced-Dose Docetaxel Followed by Radical Prostatectomy for Patients With Intermediate and High-Risk Prostate Cancer: A Single-Center Study. AB - BACKGROUND: To assess safety, pathologic response rate, and long-term oncologic outcomes of radical prostatectomy (RP) after neoadjuvant chemotherapy using reduced-dose docetaxel without androgen-deprivation therapy in prostate cancer (PCa) patients of intermediate- and high-risk groups. METHODS: Forty-four patients with PCa (PSA > 10 ng/ml, Gleason score 7 or more, or clinical stage cT2c or more) were included with a median follow-up of 11.4 years after RP. One group (NCT/RP) received neoadjuvant treatment 3-weekly with docetaxel (36 mg/m(2) for up to six cycles, 21 patients), the other (control) group (RP, 23 patients) received RP only. RESULTS: Toxicities were mild with grade 3 events not exceeding 10%. A statistically significant reduction of PSA > 50% post-chemotherapy was observed in 52.4% cases. Cancer-specific survival (CSS) was 90% in the NCT/RP group and 60.9% in the RP group (P = 0.042). The biochemical recurrence-free survival was 68.5% in the NCT/RP and 37.7% in the RP groups; overall survival was 75.5% and 54.6%, respectively (both P > 0.05). CONCLUSIONS: The use of neoadjuvant chemotherapy before RP in a selected regimen and dose represents a safe strategy and results in benefits in CSS. Given the limitations of the study, this concept should be evaluated in large, prospective, controlled studies. Prostate 76: 1345-1352, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864708 TI - Ultrasensitive 1D field-effect phototransistors: CH3NH3PbI3 nanowire sensitized individual carbon nanotubes. AB - Field-effect phototransistors were fabricated based on individual carbon nanotubes (CNTs) sensitized by CH3NH3PbI3 nanowires (MAPbI3NWs). These devices represent light responsivities of R = 7.7 * 10(5) A W(-1) under low-lighting conditions in the nW mm(-2) range, unprecedented among CNT-based photodetectors. At high incident power (~1 mW mm(-2)), light soaking results in a negative photocurrent, turning the device insulating. We interpret the phenomenon as a result of efficient free photoexcited charge generation and charge transfer of photoexcited holes from the perovskite to the carbon nanotube. The charge transfer improves conductance by increasing the number of carriers, but leaves electrons behind. At high illumination intensity their random electrostatic potential quenches mobility in the nanotube. PMID- 26864710 TI - Multidrug-Resistant Organism Colonization in a High-Risk Pediatric Patient Population. PMID- 26864709 TI - Euthanasia and Assisted Suicide of Patients With Psychiatric Disorders in the Netherlands 2011 to 2014. AB - IMPORTANCE: Euthanasia or assisted suicide (EAS) of psychiatric patients is increasing in some jurisdictions such as Belgium and the Netherlands. However, little is known about the practice, and it remains controversial. OBJECTIVES: To describe the characteristics of patients receiving EAS for psychiatric conditions and how the practice is regulated in the Netherlands. DESIGN, SETTING, AND PARTICIPANTS: This investigation reviewed psychiatric EAS case summaries made available online by the Dutch regional euthanasia review committees as of June 1, 2015. Two senior psychiatrists used directed content analysis to review and code the reports. In total, 66 cases from 2011 to 2014 were reviewed. MAIN OUTCOMES AND MEASURES: Clinical and social characteristics of patients, physician review process of the patients' requests, and the euthanasia review committees' assessments of the physicians' actions. RESULTS: Of the 66 cases reviewed, 70% (n = 46) were women. In total, 32% (n = 21) were 70 years or older, 44% (n = 29) were 50 to 70 years old, and 24% (n = 16) were 30 to 50 years old. Most had chronic, severe conditions, with histories of attempted suicides and psychiatric hospitalizations. Most had personality disorders and were described as socially isolated or lonely. Depressive disorders were the primary psychiatric issue in 55% (n = 36) of cases. Other conditions represented were psychotic, posttraumatic stress or anxiety, somatoform, neurocognitive, and eating disorders, as well as prolonged grief and autism. Comorbidities with functional impairments were common. Forty-one percent (n = 27) of physicians performing EAS were psychiatrists. Twenty-seven percent (n = 18) of patients received the procedure from physicians new to them, 14 of whom were physicians from the End-of-Life Clinic, a mobile euthanasia clinic. Consultation with other physicians was extensive, but 11% (n = 7) of cases had no independent psychiatric input, and 24% (n = 16) of cases involved disagreement among consultants. The euthanasia review committees found that one case failed to meet legal due care criteria. CONCLUSIONS AND RELEVANCE: Persons receiving EAS for psychiatric disorders in the Netherlands are mostly women and of diverse ages, with complex and chronic psychiatric, medical, and psychosocial histories. The granting of their EAS requests appears to involve considerable physician judgment, usually involving multiple physicians who do not always agree (sometimes without independent psychiatric input), but the euthanasia review committees generally defer to the judgments of the physicians performing the EAS. PMID- 26864711 TI - Host-parasite interactions and the immunobiology of cestodes. PMID- 26864713 TI - Murder and psychosis: Neuropsychological profiles of homicide offenders with schizophrenia. AB - BACKGROUND: Neurocognitive dysfunction, a core feature of schizophrenia, is thought to contribute to the impulsive violent aggression manifested by some individuals with schizophrenia, but not enough is known about how homicidal individuals with schizophrenia perform on neuropsychological measures. AIMS: The primary aim of our study was to describe the neuropsychological profiles of homicide offenders with schizophrenia. Supplementary analyses compared the criminal, psychiatric and neuropsychological features of schizophrenic homicide offenders with and without God/Satan/demon-themed psychotic symptoms. METHODS: Twenty-five men and women diagnosed with schizophrenia who had killed another person - 21 convicted of first-degree murder and 4 found not guilty by reason of insanity - completed neuropsychological testing during forensic evaluations. RESULTS: The sample was characterised by extensive neurocognitive impairments, involving executive dysfunction (60%), memory dysfunction (68%) and attentional dysfunction (50%), although those with God/Satan/demon-themed psychotic symptoms performed better than those with nonreligious psychotic content. CONCLUSIONS: Our findings indicate that impaired cognition may play an important role in the commission of homicide by individuals with schizophrenia. A subgroup with God/Satan/demon delusions seem sufficiently less impaired that they might be able to engage in metacognitive treatment approaches, aimed at changing their relationship to their psychotic symptoms, thus reducing the perception of power and omnipotence of hallucinated voices and increasing their safety. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864714 TI - Injuries Reported and Recorded for Adults with Intellectual Disabilities Who Live with Paid Support in Scotland: a Comparison with Scottish Adults in the General Population. AB - BACKGROUND: Providers of supported living services to adults with intellectual disabilities (IDs) in the United Kingdom have procedures in place to monitor injuries; this provides opportunity to learn about the injuries being reported and recorded. The aim was to determine the incidence, causes and types of injuries experienced by 593 adults with intellectual disabilities who live with paid support in a 12-month period. METHOD: Injury data, collected via a standard electronic injury monitoring system, were compared with data collected for a matched sample of the general population in the same year. RESULTS: The adults with intellectual disabilities experienced a higher rate of injury. Falls were the commonest cause of injury for both samples, but significantly more so for the adults with intellectual disabilities. CONCLUSIONS: The higher rate of injuries, particularly minor injuries, being reported suggests a culture of injury reporting and recording within these supported living services. Electronic injury monitoring is recommended for organizations providing supported living services for adults with intellectual disabilities. PMID- 26864715 TI - Barrier Function and Natural Moisturizing Factor Levels After Cumula-tive Exposure to Short-chain Aliphatic Alcohols and Detergents: Results of Occlusion modified Tandem Repeated Irritation Test. AB - Alcohol-based disinfectants and detergents are common workplace factors for irritant contact dermatitis (ICD). Though occlusion and water are relevant co exposures, the tandem effects of occlusion and sequential exposure to alcohols and detergents have not been studied. We therefore investigated the combined effects of occlusion with water and repeated exposure to n-propanol and/or sodium lauryl sulphate (SLS) in an occlusion-modified tandem irritation test. The outcomes included visual scoring, measurement of erythema, transepidermal water loss, capacitance and natural moisturizing factor (NMF) levels. Occlusion abrogated the skin barrier function and significantly enhanced the irritant induced barrier damaging effects. The NMF levels of all irritant-exposed fields decreased significantly compared with the non-exposed fields; occlusion enhanced the decrease in NMF. Although SLS exerted more pronounced effects on the measured parameters, the barrier function impairment and NMF decrease after exposure to n propanol in workplace-relevant concentrations, found in the study, confirm the significance of short-chain aliphatic alcohols for occupational ICD. PMID- 26864716 TI - Predictions of the physicochemical properties of amino acid side chain analogs using molecular simulation. AB - A candidate drug compound is released for clinical trails (in vivo activity) only if its physicochemical properties meet desirable bioavailability and partitioning criteria. Amino acid side chain analogs play vital role in the functionalities of protein and peptides and as such are important in drug discovery. We demonstrate here that the predictions of solvation free energies in water, in 1-octanol, and self-solvation free energies computed using force field-based expanded ensemble molecular dynamics simulation provide good accuracy compared to existing empirical and semi-empirical methods. These solvation free energies are then, as shown here, used for the prediction of a wide range of physicochemical properties important in the assessment of bioavailability and partitioning of compounds. In particular, we consider here the vapor pressure, the solubility in both water and 1-octanol, and the air-water, air-octanol, and octanol-water partition coefficients of amino acid side chain analogs computed from the solvation free energies. The calculated solvation free energies using different force fields are compared against each other and with available experimental data. The protocol here can also be used for a newly designed drug and other molecules where force field parameters and charges are obtained from density functional theory. PMID- 26864718 TI - Iron deficiency anemia in newly diagnosed celiac disease in children. AB - BACKGROUND: Celiac disease (CD) in children may occur with a wide spectrum of clinical manifestations: anemia is the most frequent extraintestinal manifestation, iron deficiency anemia (IDA) is the common presentation. In our study we aimed to assess IDA condition in a large cohort of pediatric patients with newly diagnosed CD. METHODS: Our study includes a cohort of 518 children (340 females and 178 males), 6 months-18 years old, joined between January 1990 and January 2013. We have analyzed hematological parameters and iron balance: serum iron, serum ferritin and serum transferrin levels. The diagnosis of IDA was considered on the basis of hemoglobin levels below -2SD, associated with serum iron and ferritin reduction, serum transferrin increase; all compared with the normal reference values for age. RESULTS: Of all patients, 156 patients (30.1%) had anemia, including 103 females (19.8%) and 53 males (10.2%); of these, 112 (21.62%) had IDA (in 18 cases associated with alpha- or beta-thalassemia trait), 22 were thalassemic trait without iron deficiency and the remaining 19 suffered from other forms of anemia. One hundred fifteen patients (22.20%) with low ferritin levels but normal hemoglobin levels were considered as preanemic iron deficient patients. CONCLUSION: Our data confirm that iron depletion and IDA represent a frequent finding at the diagnosis of CD. This significant relation existing between CD and iron deficiency should be considered by pediatricians at the diagnosis of CD in order to treat the patients. PMID- 26864717 TI - A Mendelian randomization study of testosterone and cognition in men. AB - Testosterone replacement for older men is increasingly common, with some observations suggesting a protective effect on cognitive function. We examined the association of endogenous testosterone with cognitive function among older men in a Mendelian randomization study using a separate-sample instrumental variable (SSIV) analysis estimator to minimize confounding and reverse causality. A genetic score predicting testosterone was developed in 289 young Chinese men from Hong Kong, based on selected testosterone-related single nucleotide polymorphisms (rs10046, rs1008805 and rs1256031). The association of genetically predicted testosterone with delayed 10-word recall score and Mini-Mental State Examination (MMSE) score was assessed at baseline and follow-up using generalized estimating equation among 4,212 older Chinese men from the Guangzhou Biobank Cohort Study. Predicted testosterone was not associated with delayed 10-word recall score (-0.02 per nmol/L testosterone, 95% confidence interval (CI) -0.06 0.02) or MMSE score (0.06, 95% CI -0.002-0.12). These estimates were similar after additional adjustment for age, education, smoking, use of alcohol, body mass index and the Framingham score. Our findings do not corroborate observed protective effects of testosterone on cognitive function among older men. PMID- 26864719 TI - Body experiences and psychopathology in idiopathic central precocious and early puberty. AB - BACKGROUND: Idiopathic central precocious (PP) and early puberty (EP) are frequently associated with psychopathological problems. The aim of this study was to evaluate the quality of body experiences and psychological aspects in girls with PP and EP, as well as the impact of these conditions on their families and the subjects' vulnerability. METHODS: Subjects with PP or EP, aged 7-15 years, were evaluated through the administration of a self-report questionnaire (Children's Depression Inventory, CDI), along with a projective test (Human Figure Drawing Test, HFDT). Their parents filled in a questionnaire about their child's behavior (Child Behavior Checklist 4-18, CBCL). RESULTS: Twenty-nine girls with PP or EP were compared to 55 age-matched healthy girls. The 13.8% of subjects with EP or PP presented depressive traits, and the 48.3% reported suicidal thoughts at the CDI (vs. CONTROLS: P<0.05). At the HFDT, a lower psychological maturity and a more negative self-image, that determine a vulnerability to psychopathology and mental suffering, were observed in those subjects with a past EP or PP, who entered in adolescence. CONCLUSION: EP and PP are complex conditions, which combine somatic symptoms with negative psychological sequelae, including an increased risk for depression and a distorted body perception. The use of projective tests for the assessment of body perception might help the clinician come to a deeper understanding of the therapeutic needs of girls with PP or EP. PMID- 26864720 TI - A child presenting with primary gingivostomatitis and eczema herpeticum. PMID- 26864721 TI - Diagnosis of type C esophageal atresia despite the "successful" positioning of a nasogastric tube. PMID- 26864723 TI - Atlas Toolkit: Fast registration of 3D morphological datasets in the absence of landmarks. AB - Image registration is a gateway technology for Developmental Systems Biology, enabling computational analysis of related datasets within a shared coordinate system. Many registration tools rely on landmarks to ensure that datasets are correctly aligned; yet suitable landmarks are not present in many datasets. Atlas Toolkit is a Fiji/ImageJ plugin collection offering elastic group-wise registration of 3D morphological datasets, guided by segmentation of the interesting morphology. We demonstrate the method by combinatorial mapping of cell signalling events in the developing eyes of chick embryos, and use the integrated datasets to predictively enumerate Gene Regulatory Network states. PMID- 26864722 TI - Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae. AB - Accurate perception of taste information is crucial for animal survival. In adult Drosophila, gustatory receptor neurons (GRNs) perceive chemical stimuli of one specific gustatory modality associated with a stereotyped behavioural response, such as aversion or attraction. We show that GRNs of Drosophila larvae employ a surprisingly different mode of gustatory information coding. Using a novel method for calcium imaging in the larval gustatory system, we identify a multimodal GRN that responds to chemicals of different taste modalities with opposing valence, such as sweet sucrose and bitter denatonium, reliant on different sensory receptors. This multimodal neuron is essential for bitter compound avoidance, and its artificial activation is sufficient to mediate aversion. However, the neuron is also essential for the integration of taste blends. Our findings support a model for taste coding in larvae, in which distinct receptor proteins mediate different responses within the same, multimodal GRN. PMID- 26864724 TI - C15078. Essential oil composition of Phagnalon sordidum (L.) from Corsica, chemical variability and antimicrobial activity. AB - The chemical composition of Phagnalon sordidum (L.) essential oil was investigated for the first time using gas chromatography and chromatography-mass spectrometry. Seventy-six compounds, which accounted for 87.9% of the total amount, were identified in a collective essential oil of P. sordidum from Corsica. The main essential oil components were (E)-beta-caryophyllene (14.4%), beta-pinene (11.0%), thymol (9.0%), and hexadecanoic acid (5.3%). The chemical compositions of essential oils from 19 Corsican locations were investigated. The study of the chemical variability using statistical analysis allowed identifying direct correlation between the three populations of P. sordidum widespread in Corsica and the essential oil compositions they produce. The in vitro antimicrobial activity of P. sordidum essential oil was evaluated and exhibited a notable activity on a large panel of clinically significant microorganisms. This article is protected by copyright. All rights reserved. PMID- 26864725 TI - Targeting NOTCH1 in T-ALL: Starving the dragon. PMID- 26864726 TI - Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: an in vivo mechanism study. AB - Context Ethnopharmacological studies have demonstrated that plants of the Combretum genus presented antidiabetic activity, including Combretum lanceolatum Pohl ex Eichler (Combretaceae). Objective This study investigated the hepatic mechanisms of action of C. lanceolatum flowers ethanol extract (ClEtOH) related to its antihyperglycaemic effect in streptozotocin-diabetic rats. Materials and methods Male Wistar rats were divided into normal (N) and diabetic control (DC) rats treated with vehicle (water); diabetic rats treated with 500 mg/kg metformin (DMet) or 500 mg/kg ClEtOH (DT500). After 21 d of treatment, hepatic glucose and urea production were investigated through in situ perfused liver with l glutamine. Changes in the phosphoenolpyruvate carboxykinase (PEPCK) levels and in the activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-signalling intermediates were also investigated. Results Similar to DMet, DT500 rats showed a reduction in the rates of hepatic production of glucose (46%) and urea (22%) in comparison with DC. This reduction was accompanied by a reduction in the PEPCK levels in liver of DT500 (28%) and DMet (43%) when compared with DC. AMPK phosphorylation levels were higher in the liver of DT500 (17%) and DMet (16%) rats. The basal AKT phosphorylation levels were increased in liver of DT500 rats, without differences in the insulin-stimulated AKT phosphorylation and in the insulin receptor levels between DC and DT500 rats. Discussion and conclusion The antidiabetic activity of ClEtOH can be attributed, at least in part, to inhibition of hepatic gluconeogenesis, probably due to the activation of both AMPK and AKT effectors and reduction in the PEPCK levels. PMID- 26864727 TI - Kinetics of postdiagnosis platelet count with overall survival of pancreatic cancer: a counting process approach. AB - The association between long-term variation of postdiagnosis platelets and survival of pancreatic cancer (PC) has never been discussed by using dynamic survival analysis method. In this retrospective study, we analyzed 311 histologically confirmed PC patients identified from a mega population-based electronic inpatients database from 2012 to 2013 in China. Counting process approach was applied to restructure the original survival data, the association between post-diagnosis platelet count and overall survival (OS) of PC was evaluated by multiple failure-time Cox proportional hazards model. After counting process adjustment, multiple failure-time Cox proportional hazards model revealed that, regardless of the treatment modalities PC patients received, postdiagnosis thrombocytopenia was prominently associated with OS, compared with PC patients with normally ranged platelet count, the HRs ranged from 2.04 (95% CI: 1.14-3.67) to 10.82 (95% CI: 2.63-44.54), and this inverse association was robust based on further sensitivity analysis. On the contrary, the association between thrombocytosis and OS of PC tended to be inconclusive. Our findings suggested that postdiagnosis thrombocytopenia was associated with significantly compromised survival among PC patients from this large retrospective cohort. Underlying mechanisms behind this association should be further investigated. PMID- 26864728 TI - Randomized clinical trial of prehabilitation before planned liver resection. AB - BACKGROUND: Patients with low fitness as assessed by cardiopulmonary exercise testing (CPET) have higher mortality and morbidity after surgery. Preoperative exercise intervention, or prehabilitation, has been suggested as a method to improve CPET values and outcomes. This trial sought to assess the capacity of a 4 week supervised exercise programme to improve fitness before liver resection for colorectal liver metastasis. METHODS: This was a randomized clinical trial assessing the effect of a 4-week (12 sessions) high-intensity cycle, interval training programme in patients undergoing elective liver resection for colorectal liver metastases. The primary endpoint was oxygen uptake at the anaerobic threshold. Secondary endpoints included other CPET values and preoperative quality of life (QoL) assessed using the SF-36(r). RESULTS: Thirty-eight patients were randomized (20 to prehabilitation, 18 to standard care), and 35 (25 men and 10 women) completed both preoperative assessments and were analysed. The median age was 62 (i.q.r. 54-69) years, and there were no differences in baseline characteristics between the two groups. Prehabilitation led to improvements in preoperative oxygen uptake at anaerobic threshold (+1.5 (95 per cent c.i. 0.2 to 2.9) ml per kg per min) and peak exercise (+2.0 (0.0 to 4.0) ml per kg per min). The oxygen pulse (oxygen uptake per heart beat) at the anaerobic threshold improved (+0.9 (0.0 to 1.8) ml/beat), and a higher peak work rate (+13 (4 to 22) W) was achieved. This was associated with improved preoperative QoL, with the overall SF-36(r) score increasing by 11 (95 per cent c.i. 1 to 21) (P = 0.028) and the overall SF-36(r) mental health score by 11 (1 to 22) (P = 0.037). CONCLUSION: A 4-week prehabilitation programme can deliver improvements in CPET scores and QoL before liver resection. This may impact on perioperative outcome. REGISTRATION NUMBER: NCT01523353 (https://clinicaltrials.gov). PMID- 26864730 TI - Rapid Swelling of Infarcted Myocardium Soon after Primary Percutaneous Coronary Intervention: A Sign of Critical Reperfusion Hemorrhage. PMID- 26864731 TI - Amine-bis(phenolate) Iron(III)-Catalyzed Formal Hydroamination of Olefins. AB - A practical synthesis of highly functionalized amines by the formal hydroamination reaction of alkenes with nitroarenes catalyzed by an air stable amine-bis(phenolate) iron(III) complex is reported. The reaction uses an easily handled silane, low catalyst loadings, and mild reaction conditions. A wide range of substrates are transformed with synthetically useful yields (21 examples). PMID- 26864729 TI - Bloodstream infections in patients with liver cirrhosis. AB - Bloodstream infections are a serious complication in patients with liver cirrhosis. Dysregulated intestinal bacterial translocation is the predominant pathophysiological mechanism of infections in this setting. For this reason enteric Gram-negative bacteria are commonly encountered as the first etiological cause of infection. However, through the years, the improvement in the management of cirrhosis, the recourse to invasive procedures and the global spread of multidrug resistant pathogens have importantly changed the current epidemiology. Bloodstream infections in cirrhotic patients are characterized by high mortality rate and complications including metastatic infections, infective endocarditis, and endotipsitis (or transjugular intrahepatic portosystemic shunt-related infection). For this reason early identification of patients at risk for mortality and appropriated therapeutic management is mandatory. Liver cirrhosis can significantly change the pharmacokinetic behavior of antimicrobials. In fact hypoproteinaemia, ascitis and third space expansion and impairment of renal function can be translated in an unpredictable drug exposure. PMID- 26864734 TI - Multifunctionalized CMCht/PAMAM Dendrimer Nanoparticles Modulate the Cellular Uptake by Astrocytes and Oligodendrocytes in Primary Cultures of Glial Cells. PMID- 26864732 TI - Perspectives on heterococcolith geochemical proxies based on high-resolution X ray fluorescence mapping. AB - Heterococcoliths are micron-scale calcite platelets produced by coccolithophores. They have been the most abundant and continuous fossil record over the last 215 million years (Myr), offering great potential for geochemical studies, although the heterococcolith fossil record remains underutilised in this domain. We have mapped heterococcoliths' composition using X-ray fluorescence (XRF) with a 100-nm resolution beam to decipher element distributions in heterococcoliths and to investigate the potential development of geochemical proxies for palaeoceanography. The study presents two Middle Jurassic Watznaueria britannica heterococcoliths from Cabo Mondego, Portugal. XRF analysis was performed with a 17 keV incident energy beam at the European Synchrotron Radiation Facility ID22NI beamline to study elements from Sr down to S. Ca, Sr and Mn are distributed following the heterococcolith crystalline arrangement. Cl, Br and S display an homogeneous distribution, whereas K, Fe, Cu, Zn and Rb are concentrated at the edges and in the central area of the heterococcoliths. Distributions of K, Fe, Ti, Fe, Cu, Zn, Rb and to a lesser extent V and Cr are highly influenced by clay contamination and peripheral diagenetic overgrowth. Mn is related to diagenetic Mn-rich CaCO3 overgrowth on top of or between heterococcoliths shields. Cl and Br are likely to be present in heterococcoliths inside interstitial nano-domains. We assume that the cytoplasm [Cl(-) ] and [Br(-) ] are mediated and constant during heterococcolithogenesis. Assuming a linear correlation between cytoplasm [Cl(-) ] and sea water [Cl(-) ], heterococcolith Cl may have potential as a salinity proxy. As S is incorporated into heterococcoliths by sulphated polysaccharides, our study suggests a role for such polysaccharides in heterococcolithogenesis for at least 170 Myr. The low Sr/Ca in the W. britannica specimens studied here may either highlight an unusual cellular physiology of Mesozoic coccolithophores or result from low growth rates in oligotrophic environments. PMID- 26864735 TI - Probing electron-phonon excitations in molecular junctions by quantum interference. AB - Electron-phonon coupling is a fundamental inelastic interaction in condensed matter and in molecules. Here we probe phonon excitations using quantum interference in electron transport occurring in short chains of anthraquinone based molecular junctions. By studying the dependence of molecular junction's conductance as a function of bias voltage and temperature, we show that inelastic scattering of electrons by phonons can be detected as features in conductance resulting from quenching of quantum interference. Our results are in agreement with density functional theory calculations and are well described by a generic two-site model in the framework of non-equilibrium Green's functions formalism. The importance of the observed inelastic contribution to the current opens up new ways for exploring coherent electron transport through molecular devices. PMID- 26864736 TI - The effect of acupuncture on postoperative nausea and vomiting after pediatric tonsillectomy: A meta-analysis and systematic review. AB - OBJECTIVES/HYPOTHESIS: Tonsillectomy is one of the most frequently performed pediatric surgical procedures worldwide. The complications of this procedure include postoperative nausea and vomiting (PONV) and pain; therefore, both the treatment and prevention of PONV are important. Classical antiemetics include drug therapies such as ondansetron, which are undesirable because they often carry a high cost and several side effects. Therefore, in this study we aimed to evaluate the antiemetic effect of acupuncture after pediatric tonsillectomy. METHODS: We searched for eligible articles that reported on the antiemetic effects of acupuncture after tonsillectomy using the three databases, MEDLINE, Embase, and Cochrane, through July 2015. We included full-length original articles with adequate data for evaluating the antiemetic effects on pediatric tonsillectomy in the form of a relative ratio. The Newcastle-Ottawa scale was used to assess the quality of case control and cohort studies, and the Cochrane risk of bias tool was employed for randomized controlled trials (RCTs). RESULTS: The search identified 415 publications. After screening, we selected eight articles for review (4 RCTs, 3 prospective cohorts, and 1 pilot study). A meta analysis of acupuncture in pediatric tonsillectomy revealed that the number of patients with PONV was significantly reduced with acupuncture compared to the control group, with a risk ratio of 0.77 (95% confidence interval: 0.63-0.94, P < 0.05). CONCLUSION: When acupuncture at PC6 (neiguan) was used to prevent PONV after pediatric tonsillectomy, the risk ratio was significantly lower compared to that of conventional drug therapy. Although further randomized controlled trials are needed, acupuncture at PC6 is considered an economic and effective treatment for emesis after pediatric tonsillectomy. Laryngoscope, 126:1761-1767, 2016. PMID- 26864737 TI - Combined ultrasound-targeted microbubble destruction and polyethylenimine mediated plasmid DNA delivery to the rat retina: enhanced efficiency and accelerated expression. AB - BACKGROUND: Gene therapy has potential in the treatment of refractory retinal diseases. It is important to develop an effective delivery system in the retina. The present study aimed to investigate the efficacy and safety of ultrasound (US) targeted microbubble destruction (UTMD)-mediated polyethylenimine (PEI) to the rat retina. METHODS: Gene transfer was examined by injecting PEI/plasmid DNA (pDNA) with or without microbubbles (MBs) into the subretinal space of rats that were then exposed to US. We investigated enhanced green fluorescent protein (eGFP) expression on flat fundus oculi and performed quantitative analysis. Hematoxylin and eosin staining was used to observe tissue damage. RESULTS: UTMD significantly enhanced PEI/pDNA transfection efficiency safely by increasing both the transgene expression per cell and the percentage of transfected cells of the retina. PEI/pDNA combined with UTMD significantly increased the number of DNA gene copies and the mRNA level in the retinal pigment epithelium (RPE) and neural retina, respectively, compared to PEI/pDNA alone. CONCLUSIONS: The present study demonstrates that enhanced and accelerated pDNA expression can be achieved in the retina/RPE cells in vivo by UTMD physical techniques combined with a PEI chemical vector. Our study provides useful information for further in vivo retinal gene therapy work. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864738 TI - Elevated blood lead and cadmium levels associated with chronic infections among non-smokers in a cross-sectional analysis of NHANES data. AB - BACKGROUND: Experimental animal studies, in vitro experiments, and clinical assessments have shown that metal toxicity can impair immune responses. We analyzed data from a United States representative National Health and Nutrition Examination Survey (NHANES) to explore associations between chronic infections and elevated blood concentrations of lead and cadmium among non-smoking NHANES participants. METHODS: NHANES data from 1999 to 2012 were examined and weighted to represent the United States population. Multivariable logistic regression was used to estimate adjusted odds ratios (AOR) and 95 % confidence intervals (CI) for heavy metal associations with seropositivity for Helicobacter pylori, Toxoplasma gondii, and Hepatitis B virus (HBV) infections. RESULTS: Available 2 year survey cycles for infection seroprevalence varied by pathogen, from 1 to 7 cycles. Available sample size, disease seroprevalence, and participant age range also varied by pathogen of interest. After controlling for demographic characteristics and general health condition, an elevated blood lead level above the survey population median was significantly associated with seropositivity for all three pathogens (AORs = 1.2-1.5). In addition, an elevated blood cadmium level above the median was significantly associated with HBV (AOR = 1.5; 95 % CI = 1.2-2.0) and H. pylori (AOR = 1.5; 95 % CI = 1.2-1.7) seropositivity. Age specific analyses for H. pylori and T. gondii indicated stronger associations among children under 13 years of age, particularly for lead exposure and H. pylori seropositivity, and weaker associations among those over 35 years of age. CONCLUSIONS: The results of this cross-sectional human health survey suggest that the immunological effects of lead and cadmium toxicity may be associated with an increased susceptibility to chronic infections. PMID- 26864739 TI - Failure to thrive as presentation in a patient with 22q11.2 microdeletion. AB - BACKGROUND: Abnormalities of chromosome 22q11, including deletions and translocations, have been described in association with different birth defects and malformations occurring in many combinations and degrees of severity. CASE PRESENTATION: We describe the case of an 8 month-old infant with no dysmorphic signs who showed progressive postnatal growth failure and no chronic systemic diseases. We found a 22q11.2 microdeletion, inherited from the mother, suggesting the diagnosis of DiGeorge syndrome. The patient had an isolated growth hormone (GH) deficiency and a significant increase in linear growth during the first and the second year of GH therapy, and a recovery of weight was shown. CONCLUSIONS: Sometimes, in infants with growth failure a genetic analysis is strongly suggested, since chromosomal abnormalities may be present. PMID- 26864740 TI - Interlinkage among cardio-metabolic disease markers in an urban poor setting in Nairobi, Kenya. AB - INTRODUCTION: The main cardio-metabolic diseases - mostly cardiovascular diseases such as stroke and ischemic heart disease - share common clinical markers such as raised blood pressure and blood glucose. The pathways of development of many of these conditions are also interlinked. In this regard, a higher level of co occurrence of the main cardio-metabolic disease markers is expected. Evidence about the patterns of occurrence of cardio-metabolic markers and their interlinkage in the sub-Saharan African setting is inadequate. OBJECTIVE: The goal of the study was to describe the interlinkage among common cardio-metabolic disease markers in an African setting. DESIGN: We used data collected in a cross sectional study from 5,190 study participants as part of cardiovascular disease risk assessment in the urban slums of Nairobi, Kenya. Five commonly used clinical markers of cardio-metabolic conditions were considered in this analysis. These markers were waist circumference, blood pressure, random blood glucose, total blood cholesterol, and triglyceride levels. Patterns of these markers were described using means, standard deviations, and proportions. The associations between the markers were determined using odds ratios. RESULTS: The weighted prevalence of central obesity, hypertension, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia were 12.3%, 7.0%, 2.5%, 10.3%, and 17.3%, respectively. Women had a higher prevalence of central obesity and hypercholesterolemia as compared to men. Blood glucose was strongly associated with central obesity, blood pressure, and triglyceride levels, whereas the association between blood glucose and total blood cholesterol was not statistically significant. CONCLUSIONS: This study shows that most of the common cardio-metabolic markers are interlinked, suggesting a higher probability of comorbidity due to cardio metabolic conditions and thus the need for integrated approaches. PMID- 26864741 TI - Dual contraceptive method use in HIV-serodiscordant Kenyan couples. AB - BACKGROUND: World Health Organization (WHO) guidelines recommend dual contraceptive method use with condoms and another contraceptive to reduce both incidence of HIV/sexually transmitted infection transmission and unintended pregnancies. This qualitative study assessed the barriers to and motivations for dual contraceptive use in Kenyan HIV-serodiscordant couples. METHODS: HIV serodiscordant couples in Nairobi, Kenya, were recruited from two longitudinal cohorts. Qualitative semistructured interviews were conducted using a semistructured questionnaire. Twelve male and 12 female members of serodiscordant couples and 10 women with incident pregnancies during the cohort studies were included. RESULTS: Few couples reported using dual contraceptive methods, with men reporting more condom use than women. No HIV-seropositive men or HIV seronegative women reported using non-condom contraception. Men and women agreed that men play a dominant role in decisions to use both condoms and contraception in HIV-serodiscordant couples. Participants reported that perceptions of side effects, male partner preference, and reproductive desire were critical factors in contraceptive decisions. Both men and women saw dual contraceptive method use as redundant and a sign of possible unfaithfulness. Many participants actively desired pregnancy, but few were able to accurately define monthly fertility windows. CONCLUSIONS: Dual contraceptive method use was low in these HIV serodiscordant couples, with some couples finding it unnecessary while using condoms, and others being more focused on conceiving a child. Biomedical HIV prevention, including male circumcision, pre-exposure prophylaxis or antiretroviral therapy to reduce HIV transmission, may be more acceptable strategies to promote safer sexual relations among HIV-serodiscordant couples and safer conception when desired. PMID- 26864742 TI - The first metatarsophalangeal joint in gout: a systematic review and meta analysis. AB - BACKGROUND: The aim of this review was to qualitatively synthesise studies that have investigated characteristics of the first metatarsophalangeal joint (1(st) MTP) in gout and to undertake a meta-analysis to estimate the average prevalence of acute 1(st) MTP arthritis across studies in people with gout. METHODS: Studies published in English were included if they involved participants who had a diagnosis of gout and presented original findings relating to the following outcome measures associated with the 1(st) MTP: epidemiology; clinical features; structural and functional characteristics; and microscopic and imaging features. RESULTS: Forty-five studies were included in the qualitative synthesis. 1(st) MTP pain was a prominent feature in people with gout. People with 1(st) MTP gout reported walking- and general-disability. Structural and functional characteristics of 1(st) MTP gout included hallux valgus, osteoarthritis, and restricted joint motion. Successful crystal aspiration ranged from 81 to 91 % and positive crystal identification via microscopy ranged from 83 to 93 % in patients with a history of 1(st) MTP gout. Imaging features were common at the 1(st) MTP including the double contour sign, tophi and erosions. Eleven studies involving 2,325 participants were included in the meta-analysis, providing an estimate of the average prevalence of acute 1(st) MTP arthritis across studies of 73 % (95 % prediction interval 40-92 %; range 48-97 %; I(2) = 93 %). CONCLUSIONS: 1(st) MTP acute arthritis is highly prevalent in people with gout and has a substantial impact on patient-reported pain and disability. Gout affects the structure and function of the 1(st) MTP. Microscopic and imaging studies have demonstrated crystal deposition and joint damage at the 1(st) MTP in people with gout. PMID- 26864744 TI - Experimental caprine neosporosis: the influence of gestational stage on the outcome of infection. AB - Here, we assessed outcome of experimental infection by Neospora caninum in goats intravenously inoculated with 10(6) tachyzoites of the Nc-Spain7 isolate at 40 (G1), 90 (G2) and 120 (G3) days of gestation. Infected goats had fever between 5 and 9 days post inoculation (dpi); all were seropositive at the time of abortion/birth. Foetal death occurred in G1 from 10 to 21 dpi (n = 7) and in G2 from 27 to 35 dpi (n = 4). Goats in G2 also had seropositive stillbirth (n = 1) and healthy kids (n = 2). G3 goats (n = 7) had 3 seropositive and 3 seronegative weak kids, and 2 seronegative healthy kids. Parasite DNA detection in placentomes was 100% in G2, 85.7% in G3 and in G1 was detected only in placentomes from the goats with foetal losses from 17 dpi (100%). Parasites were detected in foetal/kid brain (>85.7%) and liver (>= 50%) of G2 and G3, and in G1 after 17 dpi (100%). The highest parasite loads were detected in the placentomes of G1 from 17 dpi and G2, and in foetal tissues of G1 from 17 dpi and G3. Multifocal necrotic lesions were observed in the placentas of the three groups, but they were larger and more frequent in G1 and G2. Similar lesions were observed in foetal tissues, but they were more frequent in G3. These findings suggest that, as observed in cattle and sheep, the clinical consequences of N. caninum in pregnant goats are dependent in part on the time of gestation when animals were infected. PMID- 26864743 TI - Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk. AB - In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV specific responses by intracellular cytokine staining for IFN-gamma, IL-2, and TNF-alpha. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-alpha response to the imidazoquinoline compound CL097 and beta-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-gamma+IL-2-TNF-alpha- CD8 T cells and IFN-gamma+IL-2-TNF-alpha+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals. PMID- 26864745 TI - Treat to Target in Inflammatory Bowel Disease. AB - OPINION STATEMENT: With the expanding armamentarium in IBD the current treatment targets can be reached. By optimally using our drugs we can avoid long-term complications in IBD. For this the therapeutic strategy has to be changed from a clinically driven approach to a target-driven strategy. Currently mucosal healing, normalization of biomarkers, histological healing, and healing on abdominal imaging are proposed targets. Correct phenotyping of the patient before initiation of therapy is mandatory. Once treatment is initiated a continuous re evaluation with consequent adaptation of the treatment when goals are not (yet) reached is needed. Both escalation and de-escalation should be considered. Drug levels can be used as a guidance to reach these targets. PMID- 26864746 TI - Preliminary Evidence of Decreased Disease-Specific Health-Related Quality of Life in Asymptomatic Stone Patients. AB - INTRODUCTION: Kidney stone patients have lower health-related quality of life (HRQOL) than nonstone formers. Among active stone patients (those with stones), those with symptoms have lower HRQOL than those without. However, little is known about whether asymptomatic stones affect patients' HRQOL. METHODS: A sample of asymptomatic stone formers was assembled by identifying patients who reported no symptoms on the disease-specific Wisconsin Stone Quality of Life (WiSQoL) questionnaire (n=351). Of these, 107 were identified (M:F 61:46; 53+/-17 years; BMI 29.5+/-7.6). Patients were mostly recurrent (78%), and 42% thought they had stones at the time of the WiSQoL questionnaire. Patients' WisQoL responses were compared by self-reported stone status (yes/no), actual stone status (yes/no, corroborated from imaging and medical records), age, gender, and duration of stones. RESULTS: Of patients reporting stones at the time of the questionnaire (42% of sample), 37 (82%) were correct about it. Of patients who reported not having stones (49% of sample), 29 (55%) were correct. WiSQoL results were lower (worse HRQOL) among patients with stones versus those without, regardless of whether they knew their actual stone status. CONCLUSIONS: Asymptomatic patients with current stones, whether they are aware of them or not, may have lower HRQOL. These results suggest that (a) some patients may not be fully aware of their stone-related symptoms or are better able to handle them than others, and (b) due to the potential impact on HRQOL, some patients may benefit from definitive knowledge of their stone status as this may inform decision-making for subsequent stone management. PMID- 26864748 TI - Permanent mesh has "limited utility" for vaginal prolapse repair, review finds. PMID- 26864747 TI - Evaluation of the Viabilities and Stabilities of Pathogenic Mold and Yeast Species Using Three Different Preservation Methods Over a 12-Year Period Along with a Review of Published Reports. AB - Serious mycological work requires a reliable source of cultures that are maintained under safe long-term storage. In this study, 1186 clinical fungal isolates consisting of molds (20 species in 11 genera) and yeasts (21 species in seven genera) maintained in water, under mineral oil at room temperature and cryopreserved at -80 degrees C for periods ranging from 1 to 12 years, were evaluated for their viabilities and stabilities. The strains were subcultured onto either Sabouraud dextrose agar or potato dextrose agar to determine the viabilities and purities. The stabilities of the dermatophytes were investigated using urease test medium, the Trichophyton agar test and morphological examination. The stabilities of yeasts were evaluated by microscopic morphology and by determining the antifungal susceptibilities of random samples of yeasts (n = 120). Additionally, 365 strains (dermatophytes, n = 115; yeasts, n = 250) were further characterized by "matrix-assisted laser desorption/ionization time-of flight mass spectrometry." After 12 years of preservation, the survival rates with the three different preservation techniques, i.e., in water, under mineral oil and by freezing, were assessed as 94.7, 82.0 and 97.4 %, respectively. Viability was generally unrelated to the duration of storage. More stable and consistent growth was achieved after storage in water and freezing compared with mineral oil preservation. Our results demonstrate that the procedure for maintaining fungal cultures in water is a simple and inexpensive method, next to cryopreservation, and that both can be reliably used for the long-term preservation of most fungal isolates. PMID- 26864750 TI - Comparative Investigation of the Ionicity of Aprotic and Protic Ionic Liquids in Molecular Solvents by using Conductometry and NMR Spectroscopy. AB - Electrical conductivity (sigma), viscosity (eta), and self-diffusion coefficient (D) measurements of binary mixtures of aprotic and protic imidazolium-based ionic liquids with water, dimethyl sulfoxide, and ethylene glycol were measured from 293.15 to 323.15 K. The temperature dependence study reveals typical Arrhenius behavior. The ionicities of aprotic ionic liquids were observed to be higher than those of protic ionic liquids in these solvents. The aprotic ionic liquid, 1 butyl-3-methylimidazolium tetrafluoroborate, [bmIm][BF4 ], displays 100 % ionicity in both water and ethylene glycol. The protic ionic liquids in both water and ethylene glycol are classed as good ionic candidates, whereas in DMSO they are classed as having a poor ionic nature. The solvation dynamics of the ionic species of the ionic liquids are illustrated on the basis of the (1) H NMR chemical shifts of the ionic liquids. The self-diffusion coefficients D of the cation and anion of [HmIm][CH3 COO] in D2 O and in [D6 ]DMSO are determined by using (1) H nuclei with pulsed field gradient spin-echo NMR spectroscopy. PMID- 26864749 TI - Broadband perfect light trapping in the thinnest monolayer graphene-MoS2 photovoltaic cell: the new application of spectrum-splitting structure. AB - The light absorption of a monolayer graphene-molybdenum disulfide photovoltaic (GM-PV) cell in a wedge-shaped microcavity with a spectrum-splitting structure is investigated theoretically. The GM-PV cell, which is three times thinner than the traditional photovoltaic cell, exhibits up to 98% light absorptance in a wide wavelength range. This rate exceeds the fundamental limit of nanophotonic light trapping in solar cells. The effects of defect layer thickness, GM-PV cell position in the microcavity, incident angle, and lens aberration on the light absorptance of the GM-PV cell are explored. Despite these effects, the GM-PV cell can still achieve at least 90% light absorptance with the current technology. Our proposal provides different methods to design light-trapping structures and apply spectrum-splitting systems. PMID- 26864751 TI - Alternative interpretations for decreasing voltage with increasing charge in ferroelectric capacitors. AB - Recent claim on the direct observation of a negative capacitance (NC) effect from a single layer epitaxial Pb(Zr0.2,Ti0.8)O3 (PZT) thin film was carefully reexamined, and alternative interpretations that can explain the experimental results without invoking the NC effect are provided. Any actual ferroelectric capacitor has an interfacial layer, and experiment always measures the sum of voltages across the interface layer and the ferroelectric layer. The main observation of decreasing ferroelectric capacitor voltage (VF) for increasing ferroelectric capacitor charge (QF), claimed to be the direct evidence for the NC effect, could be alternatively interpreted by either the sudden increase in the positive capacitance of a ferroelectric capacitor or decrease in the voltage across the interfacial layer due to resistance degradation. The experimental time transient VF and QF could be precisely simulated by these alternative models that fundamentally assumes the reverse domain nucleation and growth. Supplementary experiments using an epitaxial BaTiO3 film supported this claim. This, however, does not necessarily mean that the realization of the NC effect within the ferroelectric layer is impractical under appropriate conditions. Rather, the circuit suggested by Khan et al. may not be useful to observe the NC effect directly. PMID- 26864752 TI - Prenatal detection of 5q14.3 duplication including MEF2C and brain phenotype. AB - The 5q14.3 duplication is a rare condition comprising speech and developmental delay, microcephaly, and mild ventriculomegaly. The region 5q14.3 contains several genes but the predominant role for the onset of the neurodevelopmental phenotype has been attributed to MEF2C. We describe the prenatal identification of 5q14.3 duplication, including MEF2C, in a monochorionic twin pregnancy with corpus callosum anomalies, confirmed by autopsy. To the best of our knowledge, this cerebral finding has been observed for the first time in 5q14.3 duplication patients, possibly widening the neurological picture of this scarcely known syndrome. A pathogenetic role of MEF2C overexpression in brain development may be assumed, but further studies are needed. PMID- 26864753 TI - Extending the corrole ring conjugation: preparation of beta,beta'-fused 2,3 [1',2'-b]pyrazinocorroles. AB - A novel method for the preparation of corroles with beta-fused pyrazino rings was developed, exploiting a one-pot reaction of 2,3-diaminocorroles (or 2,3,17,18 tetraaminocorroles) with different diones; a variety of pi-extended corroles were obtained in moderate yields as copper complexes, which can then be demetallated to give the corresponding free base in good yields. PMID- 26864754 TI - Whisker-related afferents in superior colliculus. AB - Rodents use their whiskers to explore the environment, and the superior colliculus is part of the neural circuits that process this sensorimotor information. Cells in the intermediate layers of the superior colliculus integrate trigeminotectal afferents from trigeminal complex and corticotectal afferents from barrel cortex. Using histological methods in mice, we found that trigeminotectal and corticotectal synapses overlap somewhat as they innervate the lower and upper portions of the intermediate granular layer, respectively. Using electrophysiological recordings and optogenetics in anesthetized mice in vivo, we showed that, similar to rats, whisker deflections produce two successive responses that are driven by trigeminotectal and corticotectal afferents. We then employed in vivo and slice experiments to characterize the response properties of these afferents. In vivo, corticotectal responses triggered by electrical stimulation of the barrel cortex evoke activity in the superior colliculus that increases with stimulus intensity and depresses with increasing frequency. In slices from adult mice, optogenetic activation of channelrhodopsin-expressing trigeminotectal and corticotectal fibers revealed that cells in the intermediate layers receive more efficacious trigeminotectal, than corticotectal, synaptic inputs. Moreover, the efficacy of trigeminotectal inputs depresses more strongly with increasing frequency than that of corticotectal inputs. The intermediate layers of superior colliculus appear to be tuned to process strong but infrequent trigeminal inputs and weak but more persistent cortical inputs, which explains features of sensory responsiveness, such as the robust rapid sensory adaptation of whisker responses in the superior colliculus. PMID- 26864755 TI - Sensorimotor recalibration during split-belt walking: task-specific and multisensory? AB - Motor adaptations not only recalibrate movement execution but also can lead to altered movement perception in multiple sensory domains. Vazquez, Statton, Busgang, and Bastian (J Neurophysiol 114: 3255-3267, 2015) recently showed that split-belt walking affects perception of leg speed during walking, but not perceptions of leg position during standing and walking or perception of contact force during stepping. Considering their findings within the broader scope of sensorimotor recalibration in other tasks, we suggest that sensorimotor recalibrations are task specific and can be multisensory. PMID- 26864757 TI - Effects of transcranial direct current stimulation of primary somatosensory cortex on vibrotactile detection and discrimination. AB - Anodal transcranial direct current stimulation (a-tDCS) of primary somatosensory cortex (S1) has been shown to enhance tactile spatial acuity, but there is little information as to the underlying neuronal mechanisms. We examined vibrotactile perception on the distal phalanx of the middle finger before, during, and after contralateral S1 tDCS [a-, cathodal (c)-, and sham (s)-tDCS]. The experiments tested our shift-gain hypothesis, which predicted that a-tDCS would decrease vibrotactile detection and discrimination thresholds (leftward shift of the stimulus-response function with increased gain/slope) relative to s-tDCS, whereas c-tDCS would have the opposite effects (relative to s-tDCS). The results showed that weak a-tDCS (1 mA, 20 min) led to a reduction in both vibrotactile detection and discrimination thresholds to 73-76% of baseline during the application of the stimulation in subjects categorized as responders. These effects persisted after the end of a-tDCS but were absent 30 min later. Most, but not all, subjects showed a decrease in threshold (8/12 for detection; 9/12 for discrimination). Intersubject variability was explained by a ceiling effect in the discrimination task. c-tDCS had no significant effect on either detection or discrimination threshold. Taken together, our results supported our shift-gain hypothesis for a tDCS but not c-tDCS. PMID- 26864756 TI - Ca2+ removal by the plasma membrane Ca2+-ATPase influences the contribution of mitochondria to activity-dependent Ca2+ dynamics in Aplysia neuroendocrine cells. AB - After Ca(2+) influx, mitochondria can sequester Ca(2+) and subsequently release it back into the cytosol. This form of Ca(2+)-induced Ca(2+) release (CICR) prolongs Ca(2+) signaling and can potentially mediate activity-dependent plasticity. As Ca(2+) is required for its subsequent release, Ca(2+) removal systems, like the plasma membrane Ca(2+)-ATPase (PMCA), could impact CICR. Here we examine such a role for the PMCA in the bag cell neurons of Aplysia californica CICR is triggered in these neurons during an afterdischarge and is implicated in sustaining membrane excitability and peptide secretion. Somatic Ca(2+) was measured from fura-PE3-loaded cultured bag cell neurons recorded under whole cell voltage clamp. Voltage-gated Ca(2+) influx was elicited with a 5-Hz, 1 min train, which mimics the fast phase of the afterdischarge. PMCA inhibition with carboxyeosin or extracellular alkalization augmented the effectiveness of Ca(2+) influx in eliciting mitochondrial CICR. A Ca(2+) compartment model recapitulated these findings and indicated that disrupting PMCA-dependent Ca(2+) removal increases CICR by enhancing mitochondrial Ca(2+) loading. Indeed, carboxyeosin augmented train-evoked mitochondrial Ca(2+) uptake. Consistent with their role on Ca(2+) dynamics, cell labeling revealed that the PMCA and mitochondria overlap with Ca(2+) entry sites. Finally, PMCA-dependent Ca(2+) extrusion did not impact endoplasmic reticulum-dependent Ca(2+) removal or release, despite the organelle residing near Ca(2+) entry sites. Our results demonstrate that Ca(2+) removal by the PMCA influences the propensity for stimulus-evoked CICR by adjusting the amount of Ca(2+) available for mitochondrial Ca(2+) uptake. This study highlights a mechanism by which the PMCA could impact activity-dependent plasticity in the bag cell neurons. PMID- 26864758 TI - Response reliability observed with voltage-sensitive dye imaging of cortical layer 2/3: the probability of activation hypothesis. AB - A central assertion in the study of neural processing is that our perception of the environment directly reflects the activity of our sensory neurons. This assertion reinforces the intuition that the strength of a sensory input directly modulates the amount of neural activity observed in response to that sensory feature: an increase in the strength of the input yields a graded increase in the amount of neural activity. However, cortical activity across a range of sensory pathways can be sparse, with individual neurons having remarkably low firing rates, often exhibiting suprathreshold activity on only a fraction of experimental trials. To compensate for this observed apparent unreliability, it is assumed that instead the local population of neurons, although not explicitly measured, does reliably represent the strength of the sensory input. This assumption, however, is largely untested. In this study, using wide-field voltage sensitive dye (VSD) imaging of the somatosensory cortex in the anesthetized rat, we show that whisker deflection velocity, or stimulus strength, is not encoded by the magnitude of the population response at the level of cortex. Instead, modulation of whisker deflection velocity affects the likelihood of the cortical response, impacting the magnitude, rate of change, and spatial extent of the cortical response. An ideal observer analysis of the cortical response points to a probabilistic code based on repeated sampling across cortical columns and/or time, which we refer to as the probability of activation hypothesis. This hypothesis motivates a range of testable predictions for both future electrophysiological and future behavioral studies. PMID- 26864759 TI - Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal). AB - The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms. PMID- 26864761 TI - Associative plasticity in the human motor cortex is enhanced by concurrently targeting separate muscle representations with excitatory and inhibitory protocols. AB - Paired associative stimulation (PAS) induces changes in the excitability of human sensorimotor cortex that outlast the procedure. PAS typically involves repeatedly pairing stimulation of a peripheral nerve that innervates an intrinsic hand muscle with transcranial magnetic stimulation over the representation of that muscle in the primary motor cortex. Depending on the timing of the stimuli (interstimulus interval of 25 or 10 ms), PAS leads to either an increase (PAS25) or a decrease (PAS10) in excitability. Both protocols, however, have been associated with an increase in excitability of nearby muscle representations not specifically targeted by PAS. Based on these spillover effects, we hypothesized that an additive, excitability-enhancing effect of PAS25 applied to one muscle representation may be produced by simultaneously applying PAS25 or PAS10 to a nearby representation. In different experiments prototypical PAS25 targeting the left thumb representation [abductor pollicis brevis (APB)] was combined with either PAS25 or PAS10 applied to the left little finger representation [abductor digiti minimi (ADM)] or, in a control experiment, with PAS10 also targeting the APB. In an additional control experiment PAS10 targeted both representations. The plasticity effects were quantified by measuring the amplitude of motor evoked potentials (MEPs) recorded before and after PAS. As expected, prototypical PAS25 was associated with an increase in MEP amplitude in the APB muscle. This effect was enhanced when PAS also targeted the ADM representation but only when a different interstimulus timing (PAS10) was used. These results suggest that PAS induced plasticity is modified by concurrently targeting separate motor cortical representations with excitatory and inhibitory protocols. PMID- 26864760 TI - Frontal and motor cortex contributions to response inhibition: evidence from electrocorticography. AB - Changes in the environment require rapid modification or inhibition of ongoing behavior. We used the stop-signal paradigm and intracranial recordings to investigate response preparation, inhibition, and monitoring of task-relevant information. Electrocorticographic data were recorded in eight patients with electrodes covering frontal, temporal, and parietal cortex, and time-frequency analysis was used to examine power differences in the beta (13-30 Hz) and high gamma bands (60-180 Hz). Over motor cortex, beta power decreased, and high-gamma power increased during motor preparation for both go trials (Go) and unsuccessful stops (US). For successful stops (SS), beta increased, and high-gamma was reduced, indexing the cancellation of the prepared response. In the middle frontal gyrus (MFG), stop signals elicited a transient high-gamma increase. The MFG response occurred before the estimated stop-signal reaction time but did not distinguish between SS and US trials, likely signaling attention to the salient stop stimulus. A postresponse high-gamma increase in MFG was stronger for US compared with SS and absent in Go, supporting a role in behavior monitoring. These results provide evidence for differential contributions of frontal subregions to response inhibition, including motor preparation and inhibitory control in motor cortex and cognitive control and action evaluation in lateral prefrontal cortex. PMID- 26864762 TI - Visual ecology and potassium conductances of insect photoreceptors. AB - Voltage-activated potassium channels (Kv channels) in the microvillar photoreceptors of arthropods are responsible for repolarization and regulation of photoreceptor signaling bandwidth. On the basis of analyzing Kv channels in dipteran flies, it was suggested that diurnal, rapidly flying insects predominantly express sustained K(+) conductances, whereas crepuscular and nocturnally active animals exhibit strongly inactivating Kv conductances. The latter was suggested to function for minimizing cellular energy consumption. In this study we further explore the evolutionary adaptations of the photoreceptor channelome to visual ecology and behavior by comparing K(+) conductances in 15 phylogenetically diverse insects, using patch-clamp recordings from dissociated ommatidia. We show that rapid diurnal flyers such as the blowfly (Calliphora vicina) and the honeybee (Apis mellifera) express relatively large noninactivating Kv conductances, conforming to the earlier hypothesis in Diptera. Nocturnal and/or slow-moving species do not in general exhibit stronger Kv conductance inactivation in the physiological membrane voltage range, but the photoreceptors in species that are known to rely more on vision behaviorally had higher densities of sustained Kv conductances than photoreceptors of less visually guided species. No statistically significant trends related to visual performance could be identified for the rapidly inactivating Kv conductances. Counterintuitively, strong negative correlations were observed between photoreceptor capacitance and specific membrane conductance for both sustained and inactivating fractions of Kv conductance, suggesting insignificant evolutionary pressure to offset negative effects of high capacitance on membrane filtering with increased conductance. PMID- 26864763 TI - Nicotine inhibits potassium currents in Aplysia bag cell neurons. AB - Acetylcholine and the archetypal cholinergic agonist, nicotine, are typically associated with the opening of ionotropic receptors. In the bag cell neurons, which govern the reproductive behavior of the marine snail, Aplysia californica, there are two cholinergic responses: a relatively large acetylcholine-induced current and a relatively small nicotine-induced current. Both currents are readily apparent at resting membrane potential and result from the opening of distinct ionotropic receptors. We now report a separate current response elicited by applying nicotine to cultured bag cell neurons under whole cell voltage-clamp. This current was ostensibly inward, best resolved at depolarized voltages, presented a noncooperative dose-response with a half-maximal concentration near 1.5 mM, and associated with a decrease in membrane conductance. The unique nicotine-evoked response was not altered by intracellular perfusion with the G protein blocker GDPbetaS or exposure to classical nicotinic antagonists but was occluded by replacing intracellular K(+) with Cs(+) Consistent with an underlying mechanism of direct inhibition of one or more K(+) channels, nicotine was found to rapidly reduce the fast-inactivating A-type K(+) current as well as both components of the delayed-rectifier K(+) current. Finally, nicotine increased bag cell neuron excitability, which manifested as reduction in spike threshold, greater action potential height and width, and markedly more spiking to continuous depolarizing current injection. In contrast to conventional transient activation of nicotinic ionotropic receptors, block of K(+) channels could represent a nonstandard means for nicotine to profoundly alter the electrical properties of neurons over prolonged periods of time. PMID- 26864764 TI - Arm posture-dependent changes in corticospinal excitability are largely spinal in origin. AB - Biceps brachii motor evoked potentials (MEPs) from cortical stimulation are influenced by arm posture. We used subcortical stimulation of corticospinal axons to determine whether this postural effect is spinal in origin. While seated at rest, 12 subjects assumed several static arm postures, which varied in upper-arm (shoulder flexed, shoulder abducted, arm hanging to side) and forearm orientation (pronated, neutral, supinated). Transcranial magnetic stimulation over the contralateral motor cortex elicited MEPs in resting biceps and triceps brachii, and electrical stimulation of corticospinal tract axons at the cervicomedullary junction elicited cervicomedullary motor evoked potentials (CMEPs). MEPs and CMEPs were normalized to the maximal compound muscle action potential (Mmax). Responses in biceps were influenced by upper-arm and forearm orientation. For upper-arm orientation, biceps CMEPs were 68% smaller (P= 0.001), and biceps MEPs 31% smaller (P= 0.012), with the arm hanging to the side compared with when the shoulder was flexed. For forearm orientation, both biceps CMEPs and MEPs were 34% smaller (both P< 0.046) in pronation compared with supination. Responses in triceps were influenced by upper-arm, but not forearm, orientation. Triceps CMEPs were 46% smaller (P= 0.007) with the arm hanging to the side compared with when the shoulder was flexed. Triceps MEPs and biceps and triceps MEP/CMEP ratios were unaffected by arm posture. The novel finding is that arm posture-dependent changes in corticospinal excitability in humans are largely spinal in origin. An interplay of multiple reflex inputs to motoneurons likely explains the results. PMID- 26864765 TI - Classification of odorants across layers in locust olfactory pathway. AB - Olfactory processing takes place across multiple layers of neurons from the transduction of odorants in the periphery, to odor quality processing, learning, and decision making in higher olfactory structures. In insects, projection neurons (PNs) in the antennal lobe send odor information to the Kenyon cells (KCs) of the mushroom bodies and lateral horn neurons (LHNs). To examine the odor information content in different structures of the insect brain, antennal lobe, mushroom bodies and lateral horn, we designed a model of the olfactory network based on electrophysiological recordings made in vivo in the locust. We found that populations of all types (PNs, LHNs, and KCs) had lower odor classification error rates than individual cells of any given type. This improvement was quantitatively different from that observed using uniform populations of identical neurons compared with spatially structured population of neurons tuned to different odor features. This result, therefore, reflects an emergent network property. Odor classification improved with increasing stimulus duration: for similar odorants, KC and LHN ensembles reached optimal discrimination within the first 300-500 ms of the odor response. Performance improvement with time was much greater for a population of cells than for individual neurons. We conclude that, for PNs, LHNs, and KCs, ensemble responses are always much more informative than single-cell responses, despite the accumulation of noise along with odor information. PMID- 26864767 TI - Precaution for volume conduction in rodent cortical electroencephalography using high-density polyimide-based microelectrode arrays on the skull. AB - In humans, significant progress has been made to link spatial changes in electroencephalographic (EEG) spectral density, connectivity strength, and phase amplitude modulation to neurological, physiological, and psychological correlates. In contrast, standard rodent EEG techniques employ only few electrodes, which results in poor spatial resolution. Recently, a technique was developed to overcome this limitation in mice. This technique was based on a polyimide-based microelectrode (PBM) array applied on the mouse skull, maintaining a significant number of electrodes with consistent contact, electrode impedance, and mechanical stability. The present study built on this technique by extending it to rats. Therefore, a similar PBM array, but adapted to rats, was designed and fabricated. In addition, this array was connected to a wireless EEG headstage, allowing recording in untethered, freely moving rats. The advantage of a high-density array relies on the assumption that the signal recorded from the different electrodes is generated from distinct sources, i.e., not volume conducted. Therefore, the utility and validity of the array were evaluated by determining the level of synchrony between channels due to true synchrony or volume conduction during basal vigilance states and following a subanesthetic dose of ketamine. Although the PBM array allowed recording with high signal quality, under both drug and drug-free conditions, high synchronization existed due to volume conduction between the electrodes even in the higher spectral frequency range. Discrimination existed only between frontally and centrally/distally grouped electrode pairs. Therefore, caution should be used in interpreting spatial data obtained from high-density PBM arrays in rodents. PMID- 26864768 TI - Locomotor sequence learning in visually guided walking. AB - Voluntary limb modifications must be integrated with basic walking patterns during visually guided walking. In this study we tested whether voluntary gait modifications can become more automatic with practice. We challenged walking control by presenting visual stepping targets that instructed subjects to modify step length from one trial to the next. Our sequence learning paradigm is derived from the serial reaction-time (SRT) task that has been used in upper limb studies. Both random and ordered sequences of step lengths were used to measure sequence-specific and sequence-nonspecific learning during walking. In addition, we determined how age (i.e., healthy young adults vs. children) and biomechanical factors (i.e., walking speed) affected the rate and magnitude of locomotor sequence learning. The results showed that healthy young adults (age 24 +/- 5 yr,n= 20) could learn a specific sequence of step lengths over 300 training steps. Younger children (age 6-10 yr,n= 8) had lower baseline performance, but their magnitude and rate of sequence learning were the same compared with those of older children (11-16 yr,n= 10) and healthy adults. In addition, learning capacity may be more limited at faster walking speeds. To our knowledge, this is the first study to demonstrate that spatial sequence learning can be integrated with a highly automatic task such as walking. These findings suggest that adults and children use implicit knowledge about the sequence to plan and execute leg movement during visually guided walking. PMID- 26864766 TI - Long-latency reflexes of elbow and shoulder muscles suggest reciprocal excitation of flexors, reciprocal excitation of extensors, and reciprocal inhibition between flexors and extensors. AB - Postural corrections of the upper limb are required in tasks ranging from handling an umbrella in the changing wind to securing a wriggling baby. One complication in this process is the mechanical interaction between the different segments of the arm where torque applied at one joint induces motion at multiple joints. Previous studies have shown the long-latency reflexes of shoulder muscles (50-100 ms after a limb perturbation) account for these mechanical interactions by integrating information about motion of both the shoulder and elbow. It is less clear whether long-latency reflexes of elbow muscles exhibit a similar capability and what is the relation between the responses of shoulder and elbow muscles. The present study utilized joint-based loads tailored to the subjects' arm dynamics to induce well-controlled displacements of their shoulder and elbow. Our results demonstrate that the long-latency reflexes of shoulder and elbow muscles integrate motion from both joints: the shoulder and elbow flexors respond to extension at both joints, whereas the shoulder and elbow extensors respond to flexion at both joints. This general pattern accounts for the inherent flexion extension coupling of the two joints arising from the arm's intersegmental dynamics and is consistent with spindle-based reciprocal excitation of shoulder and elbow flexors, reciprocal excitation of shoulder and elbow extensors, and across-joint inhibition between the flexors and extensors. PMID- 26864769 TI - Neural control of visual search by frontal eye field: chronometry of neural events and race model processes. AB - We investigated the chronometry of neural processes in frontal eye fields of macaques performing double-step saccade visual search in which a conspicuous target changes location in the array on a random fraction of trials. Durations of computational processes producing a saccade to original and final target locations (GO1 and GO2, respectively) are derived from response times (RT) on different types of trials. In these data, GO2 tended to be faster than GO1, demonstrating that inhibition of the initial saccade did not delay production of the compensated saccade. Here, we measured the dynamics of visual, visuomovement, and movement neuron activity in relation to these processes by examining trials when neurons instantiated either process. First, we verified that saccades were initiated when the discharge rate of movement neurons reached a threshold that was invariant across RT and trial type. Second, the time when visual and visuomovement neurons selected the target and when movement neuron activity began to accumulate were not significantly different across trial type. Third, the interval from the beginning of accumulation to threshold of movement-related activity was significantly shorter when instantiating the GO2 relative to the GO1 process. Differences observed between monkeys are discussed. Fourth, random variation of RT was accounted for to some extent by random variation in both the onset and duration of selective activity of each neuron type but mostly by variation of movement neuron accumulation duration. These findings offer new insights into the sources of control of target selection and saccade production in dynamic environments. PMID- 26864771 TI - Electroencephalographic detection of respiratory-related cortical activity in humans: from event-related approaches to continuous connectivity evaluation. AB - The presence of a respiratory-related cortical activity during tidal breathing is abnormal and a hallmark of respiratory difficulties, but its detection requires superior discrimination and temporal resolution. The aim of this study was to validate a computational method using EEG covariance (or connectivity) matrices to detect a change in brain activity related to breathing. In 17 healthy subjects, EEG was recorded during resting unloaded breathing (RB), voluntary sniffs, and breathing against an inspiratory threshold load (ITL). EEG were analyzed by the specially developed covariance-based classifier, event-related potentials, and time-frequency (T-F) distributions. Nine subjects repeated the protocol. The classifier could accurately detect ITL and sniffs compared with the reference period of RB. For ITL, EEG-based detection was superior to airflow based detection (P < 0.05). A coincident improvement in EEG-airflow correlation in ITL compared with RB (P < 0.05) confirmed that EEG detection relates to breathing. Premotor potential incidence was significantly higher before inspiration in sniffs and ITL compared with RB (P < 0.05), but T-F distributions revealed a significant difference between sniffs and RB only (P < 0.05). Intraclass correlation values ranged from poor (-0.2) to excellent (1.0). Thus, as for conventional event-related potential analysis, the covariance-based classifier can accurately predict a change in brain state related to a change in respiratory state, and given its capacity for near "real-time" detection, it is suitable to monitor the respiratory state in respiratory and critically ill patients in the development of a brain-ventilator interface. PMID- 26864770 TI - Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex. AB - The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451-465, 2007), including among pyramidal cell subtypes. In the present work, we used specific pharmacological blockers to test for contributions of Kv1, Kv2, or Kv4 channels to repolarization of single APs in two genetically defined subpopulations of pyramidal cells in layer 5 of mouse somatosensory cortex (etv1 and glt) as well as pyramidal cells from layer 2/3. These three subtypes differ in AP properties (Groh A, Meyer HS, Schmidt EF, Heintz N, Sakmann B, Krieger P. Cereb Cortex 20: 826-836, 2010; Guan D, Armstrong WE, Foehring RC. J Neurophysiol 113: 2014-2032, 2015) as well as laminar position, morphology, and projection targets. We asked what the roles of Kv1, Kv2, and Kv4 channels are in AP repolarization and whether the underlying mechanisms are pyramidal cell subtype dependent. We found that Kv4 channels are critically involved in repolarizing neocortical pyramidal cells. There are also pyramidal cell subtype-specific differences in the role for Kv1 channels. Only Kv4 channels were involved in repolarizing the narrow APs of glt cells. In contrast, in etv1 cells and layer 2/3 cells, the broader APs are partially repolarized by Kv1 channels in addition to Kv4 channels. Consistent with their activation in the subthreshold range, Kv1 channels also regulate AP voltage threshold in all pyramidal cell subtypes. PMID- 26864772 TI - Association between serum nitric oxide metabolites and thyroid hormones in a general population: Tehran Thyroid Study. AB - Nitric oxide participates in the regulation of thyroid function. AIMS: The purpose of this study was to determine whether there is an association between serum nitric oxide metabolites (NOx) and free thyroxine (free T4), anti-thyroid peroxidase (anti-TPO), and thyroid-stimulating hormone (TSH) levels. METHODS: Study subjects were adults, aged >=20 years, who participated in the Tehran Thyroid Study (TTS). In a cross-sectional study, in the third phase of TTS, serum NOx concentrations were measured in 1974 adult participants; pregnant women and subjects who had chronic diarrhea, cancer, weight loss, and hospitalization within the past 3 months were excluded, as were those taking medicines that affect thyroid function; the remaining 1771 subjects were grouped according to tertiles of free T4, anti-TPO, and TSH. Spearman's correlation coefficients and multivariable linear regression analysis were used to determine the relationship between serum NOx levels and free T4, anti-TPO, and TSH. RESULTS: Serum NOx levels were negatively correlated with free T4 in men (r = -0.083; p = 0.029). An inverse association between the third tertile of free T4 and NOx levels was found in both non-adjusted (beta = -0.095, p = 0.031) and multivariable-adjusted (beta = -0.094, p = 0.039) analyses, only in men. After multivariable adjustment, the third tertile of anti-TPO was significantly associated with NOx levels in women (beta = -0.067, p = 0.050). CONCLUSIONS: Based on the result, serum NOx concentration was found to be associated with free T4 in men and anti-TPO in women. PMID- 26864773 TI - Fragile X mental retardation protein controls ion channel expression and activity. AB - Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (Kv 3.1 and Kv 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary beta4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Cav 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. PMID- 26864774 TI - Attenuation of cue-induced reinstatement of nicotine seeking by URB597 through cannabinoid CB1 receptor in rats. AB - RATIONALE: The endocannabinoid system is composed of endocannabinoids (such as anandamide), their target receptors (CB1 and CB2 receptors, CB1Rs and CB2Rs), the enzymes that degrade them (fatty-acid-amide-hydrolase (FAAH) for anandamide), and an endocannabinoid transporter. FAAH inhibition has been recently identified as having a critical involvement in behaviors related to nicotine addiction and has been shown to reduce the effect of nicotine on the mesolimbic dopaminergic system via CB1R and peroxisome proliferator-activated receptor alpha (PPARalpha). Thus, inhibition of FAAH may represent a novel strategy for smoking cessation, but its mechanism of action on relapse to nicotine seeking is still unknown. OBJECTIVE: The study aims to explore the mechanism of action of the inhibitor of FAAH activity, URB597, on relapse to nicotine seeking by evaluating the effect of the CB1R, CB2R, and PPARalpha antagonists on the attenuating effect of URB597 on cue induced reinstatement of nicotine seeking in rats. RESULTS: URB597 reduced cue induced reinstatement of nicotine seeking, an effect that was reversed by the CB1R antagonist rimonabant, but not by the CB2R or PPARalpha antagonists AM630 and MK886, respectively. CONCLUSIONS: These results indicate that URB597 reduces cue-induced reinstatement in rats through a CB1 receptor-dependent mechanism, and not via CB2R or PPARalpha. Since FAAH inhibition represent a novel and promising strategy for tobacco smoking cessation, dissecting how it produces its action may lead to a better understanding of the neurobiological mechanisms underlying nicotine addiction. PMID- 26864776 TI - A survey of 0 + 5 vascular surgery residency candidates: Perceptions of an applicant pool. AB - BACKGROUND: Applications to integrated (0 + 5) vascular surgery residencies have increased, while total applications have stayed relatively constant. This survey sought to document the perceptions of 0 + 5 vascular surgery applicants. METHODS: Academic faculty conducted interviews for 0 + 5 residency match at an academic medical center in preparation for the National Resident Matching Program (NRMP) Main Residency Match. Applicant pool (n = 20) perceptions were determined with surveys. Participation was anonymous and voluntary. RESULTS: Nineteen interviewees (26.3% female: 73.7% male), age (26.8 +/- 2.6 years) responded (95% response rate). Of 19 respondents, 68% became interested in vascular surgery in their third year with 53% becoming aware of 0 + 5 programs in their third year. All respondents identified a vascular surgery attending at their institution as significant mentors. Forty-seven percent identified their mentor during their third year of medical school. All respondents felt that 0 + 5 training would prepare them adequately for the workforce and board certification exams. Almost all (89%) had plans to seek jobs immediately upon completion of residency. CONCLUSION: Applicants remained positive about their planned training and career paths. Attending vascular surgeons were identified as the strongest mentors, yet most students decided only in their third and fourth years to pursue 0 + 5 residencies. Educational debt remains a concern, and there may be consideration for a concerted effort to recruit potential candidates sooner. PMID- 26864777 TI - Novel device, a temporary guidewire fixator. AB - A novel device for distal fixation of a guidewire was tested in regards to deployment and retrieval, deposition in the blood stream and force of fixation in a pig model. Eleven pigs were subjected to full anaesthesia and heparinized to active clotting time 250-350 s. Uninterrupted blood flow during 4 h deposition was assessed by angiography and inspected for thrombus deposition upon retrieval. The force of fixation was investigated up to the level of loss of fixation (displacement force). The device was successfully deployed and retrieved in over 40 cases. In one case, an alternative method for bailout retrieval was used. Deposition for 4 h was performed, and uninterrupted blood flow was verified by angiography. No instances of arterial occlusion or thrombosis were detected. The median dislocation force was 7.6 N. No arterial rupture or dissection was detected following the loss of fixation. As a conclusion, the device was considered safe and functional in this animal test model. PMID- 26864778 TI - The effect of sequence on the ionization of guanine in DNA. AB - The accurate estimation of the ionization energies and understanding the nature of the ionized states of the nucleic acid bases (NABs) are crucial to the understanding of the DNA damage mechanism. The vertical ionization energy (VIE) of guanine is the lowest among the NABs and the ionization energies are strongly affected by the environment, such as solvation and characteristics of nearby NABs. Therefore, we investigate the sequence dependence of the VIEs of guanine in B-DNA. We use the equation of motion coupled cluster method for the estimation of ionization potential with single and double excitations (EOM-IP-CCSD) and density functional theory with dispersion corrected omegaB97x-D for the estimation of VIEs. A significant amount of non-additivity or cooperativity, directly proportional to charge delocalization, is noticed in the change in VIE due to the interaction with the nearby NABs. While the change in VIE due to base pairing originates predominantly from charge-dipole interactions, stacking between base pairs is a more complicated balance of dispersion and charge-dipole interactions as well as stabilization due to the delocalization of the positive charge. The long range interactions are however dominated by 1/r(3) distance dependence which shows the major role played by charge-dipole interactions. The extent of localization of positive holes on guanine is also estimated for various sequences. PMID- 26864779 TI - Novel electronic ferroelectricity in an organic charge-order insulator investigated with terahertz-pump optical-probe spectroscopy. AB - In electronic-type ferroelectrics, where dipole moments produced by the variations of electron configurations are aligned, the polarization is expected to be rapidly controlled by electric fields. Such a feature can be used for high speed electric-switching and memory devices. Electronic-type ferroelectrics include charge degrees of freedom, so that they are sometimes conductive, complicating dielectric measurements. This makes difficult the exploration of electronic-type ferroelectrics and the understanding of their ferroelectric nature. Here, we show unambiguous evidence for electronic ferroelectricity in the charge-order (CO) phase of a prototypical ET-based molecular compound, alpha (ET)2I3 (ET:bis(ethylenedithio)tetrathiafulvalene), using a terahertz pulse as an external electric field. Terahertz-pump second-harmonic-generation(SHG)-probe and optical-reflectivity-probe spectroscopy reveal that the ferroelectric polarization originates from intermolecular charge transfers and is inclined 27 degrees from the horizontal CO stripe. These features are qualitatively reproduced by the density-functional-theory calculation. After sub-picosecond polarization modulation by terahertz fields, prominent oscillations appear in the reflectivity but not in the SHG-probe results, suggesting that the CO is coupled with molecular displacements, while the ferroelectricity is electronic in nature. The results presented here demonstrate that terahertz-pump optical-probe spectroscopy is a powerful tool not only for rapidly controlling polarizations, but also for clarifying the mechanisms of ferroelectricity. PMID- 26864780 TI - Coordinate-based (ALE) meta-analysis of brain activation in patients with fibromyalgia. AB - There are an increasing number of neuroimaging studies that allow a better understanding of symptoms, neural correlates and associated conditions of fibromyalgia. However, the results of these studies are difficult to compare, as they include a heterogeneous group of patients, use different stimulation paradigms, tasks, and the statistical evaluation of neuroimaging data shows high variability. Therefore, this meta-analytic approach aimed at evaluating potential alterations in neuronal brain activity or structure related to pain processing in fibromyalgia syndrome (FMS) patients, using quantitative coordinate-based "activation likelihood estimation" (ALE) meta-analysis. 37 FMS papers met the inclusion criteria for an ALE analysis (1,264 subjects, 274 activation foci). A pooled ALE analysis of different modalities of neuroimaging and additional analyses according functional and structural changes indicated differences between FMS patients and controls in the insula, amygdala, anterior/mid cingulate cortex, superior temporal gyrus, the primary and secondary somatosensory cortex, and lingual gyrus. Our analysis showed consistent results across FMS studies with potential abnormalities especially in pain-related brain areas. Given that similar alterations have already been demonstrated in patients with other chronic pain conditions and the lack of adequate control groups of chronic pain subjects in most FMS studies, it is not clear however, whether these findings are associated with chronic pain in general or are unique features of patients with FMS. Hum Brain Mapp 37:1749-1758, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26864781 TI - Ictal motor sequences: Lateralization and localization values. AB - OBJECTIVE: To determine the lateralization and localization values of ictal motor sequences in the setting of focal epilepsy ending with a secondarily generalized motor seizure. METHODS: Retrospectively, the ictal motor sequences were analyzed in patients with focal epilepsy ending with a secondarily generalized motor seizure by three readers blinded to all clinical and electrographic data. One representative seizure per patient was selected. Prevalence, positive predictive value (PPV), and Fleiss Kappa for the following motor signs were calculated: version, unilateral limb tonic posturing, unilateral limb clonic seizure, figure of-4, M2e, hand dystonia, clonic asymmetric ending, and Todd's paralysis. Sequences of signs with a PPV >= 80% were then analyzed to determine their lateralization and localization values. RESULTS: A total of 47 seizures were studied. The "reliable" motor signs with a robust lateralizing value (PPV > 80%) were version, unilateral tonic posturing, M2e, unilateral clonic seizure, asymmetric clonic ending, and Todd's paralysis. Figure-of-4 and hand dystonia had a relatively low PPV, and therefore were not included in the following sequence analysis, which included only 38 patients with two or more motor signs of high PPV. Multiple combinations of temporal progression of motor signs were seen in these 38 patients, with version being the most common initial motor sign (29 of 38 patients) usually followed by M2e (15 of 29 patients), and/or a focal tonic seizure (7 of 29 patients). Accurate lateralization of the epileptogenic zone (EZ) with a PPV of 100% can be predicted when two or more reliable motor signs point to the same side. However, the various sequences of reliable motor signs did not differentiate between temporal and extratemporal epilepsy. SIGNIFICANCE: The presence of reliable ictal motor signs in focal epilepsy is extremely valuable in lateralizing the EZ, but not in determining the localization of the EZ. This is especially useful when epilepsy surgery is indicated. PMID- 26864782 TI - Spatio-temporal variation in the preservation of ancient faunal remains. AB - Palaeodemographic studies of animals using frequency distributions of radiocarbon dates are increasingly used in studies of Quaternary extinction but are complicated by taphonomic bias, or the loss of material through time. Current taphonomic models are based on the temporal frequency distributions of sediments, but bone is potentially lost at greater rates because not all sedimentary contexts preserve bone. We test the hypotheses that (i) the loss of bone over time is greater than that of sediment and (ii) this rate of loss varies geographically at large scales. We compiled radiocarbon dates on Pleistocene-aged bone from eastern Beringia (EB), the contiguous United States (CUSA) and South America (SA), from which we developed models of taphonomic loss. We find that bone is lost at greater rates than terrestrial sediment in general, but only for CUSA and SA. Bone in EB is lost at approximately the same rate as terrestrial sediments, which demonstrates the excellent preservation environments of arctic regions, presumably due to preservative effects of permafrost. These differences between bone and sediment preservation as well as between arctic and non-arctic regions should be taken into account by any research addressing past faunal population dynamics based on temporal frequency distributions. PMID- 26864783 TI - Using ancient DNA and coalescent-based methods to infer extinction. AB - DNA sequences extracted from preserved remains can add considerable resolution to inference of past population dynamics. For example, coalescent-based methods have been used to correlate declines in some arctic megafauna populations with habitat fragmentation during the last ice age. These methods, however, often fail to detect population declines preceding extinction, most likely owing to a combination of sparse sampling, uninformative genetic markers, and models that cannot account for the increasingly structured nature of populations as habitats decline. As ancient DNA research expands to include full-genome analyses, these data will provide greater resolution of the genomic consequences of environmental change and the genetic signatures of extinction. PMID- 26864784 TI - Functionally relevant responses to human facial expressions of emotion in the domestic horse (Equus caballus). AB - Whether non-human animals can recognize human signals, including emotions, has both scientific and applied importance, and is particularly relevant for domesticated species. This study presents the first evidence of horses' abilities to spontaneously discriminate between positive (happy) and negative (angry) human facial expressions in photographs. Our results showed that the angry faces induced responses indicative of a functional understanding of the stimuli: horses displayed a left-gaze bias (a lateralization generally associated with stimuli perceived as negative) and a quicker increase in heart rate (HR) towards these photographs. Such lateralized responses towards human emotion have previously only been documented in dogs, and effects of facial expressions on HR have not been shown in any heterospecific studies. Alongside the insights that these findings provide into interspecific communication, they raise interesting questions about the generality and adaptiveness of emotional expression and perception across species. PMID- 26864785 TI - Evidence of female sex pheromones and characterization of the cuticular lipids of unfed, adult male versus female blacklegged ticks, Ixodes scapularis. AB - Copulation in Ixodes scapularis involves physical contact between the male and female (on or off the host), male mounting of the female, insertion/maintenance of the male chelicerae in the female genital pore (initiates spermatophore production), and the transfer of the spermatophore by the male into the female genital pore. Bioassays determined that male mounting behavior/chelicerae insertion required direct contact with the female likely requiring non-volatile chemical cues with no evidence of a female volatile sex pheromone to attract males. Unfed virgin adult females and replete mated adult females elicited the highest rates of male chelicerae insertion with part fed virgin adult females exhibiting a much lower response. Whole body surface hexane extracts of unfed virgin adult females and males, separately analyzed by GC-MS, identified a number of novel tick surface associated compounds: fatty alcohols (1-hexadecanol and 1 heptanol), a fatty amide (erucylamid), aromatic hydrocarbons, a short chain alkene (1-heptene), and a carboxylic acid ester (5beta-androstane). These compounds are discussed in terms of their potential role in female-male communication. The two most abundant fatty acid esters found were butyl palmitate and butyl stearate present in ratios that were sex specific. Only 6 n-saturated hydrocarbons were identified in I. scapularis ranging from 10 to 18 carbons. PMID- 26864786 TI - Considering Age Variation When Coining Drugs as High versus Low Hepatic Extraction Ratio. AB - The hepatic extraction ratio (EH) is commonly considered an "inherent attribute" of drug. It determines the main physiological and biological elements of the system (patient attributes) that are most significant in interindividual variability of clearance. The EH consists of three age-dependent parameters: fraction of unbound drug in blood (fu.B), hepatic intrinsic clearance of unbound drug (CLu.int,H), and hepatic blood flow (QH). When the age-effects on these elements are not proportional, a given drug may shift from so-called high extraction status to low extraction. To demonstrate the impact of age-related changes on fu.B, CLu int,H, and QH, the EH of midazolam and two hypothetical drugs with 10-fold higher and 10-fold lower CLu.int,H than midazolam were investigated in pediatrics based on known ontogeny functions. The EH was simulated using Simcyp software, version 14. This was then complemented by a comprehensive literature survey to identify the commonly applied covariates in pediatric population pharmacokinetic (PopPK) studies. Midazolam EH decreased from 0.6 in adults to 0.02 at birth, making its clearance much more susceptible to changes in CLu.int,H and fu.B than in adults and reducing the impact of QH on clearance. The drug with 10-fold higher CLu.int,H was categorized as high extraction from 4 days old onward whereas the drug with 10-fold lower CLu.int,H remained low extraction from birth to adulthood. Approximately 50% of collected PopPK studies (n = 120) did not consider interaction between age and other covariates. Interaction between covariates and age should be considered as part of studies involving younger pediatric patients. The EH cannot be considered an inherent drug property without considering the effect of age. PMID- 26864787 TI - Hydrological cycle effects on the aquatic community in a Neotropical stream of the Andean piedmont during the 2007-2010 ENSO events. AB - The seasonal and interannual changes in the fish, macroinvertebrates and phycoperiphyton assemblages of the Guarino River were examined in relation to the physical and chemical environmental changes associated with the hydrological cycle and the El Nino-Nina/Southern Oscillation (ENSO) between 2007 and 2010. Four samplings (in dry and rainy seasons) were performed per year. Environmental variables (temperature, pH, conductivity, turbidity, oxygen, total nitrogen, orthophosphate, depth and flow rate) were measured. The temporal patterns of the taxonomic compositions for the three assemblages and the functional composition of fish and macroinvertebrate assemblages with respect to environmental variables were examined through canonical discriminant analysis, multidimensional scaling and multiple correlations. The presence and abundance of fishes, macroinvertebrates and algae species were regulated by environmental variables associated with extreme hydrological events, which derived from the natural torrential regimen of the basin and larger-scale phenomena, such as El Nino and La Nina. Fish abundance and richness were significantly correlated with algal density and pH, the macroinvertebrate density was negatively related to the flow rate and the richness was positively correlated with algal density. The algae richness was positively correlated with pH and negatively correlated with the flow rate and nitrogen. The algal density was positively correlated with pH and temperature and negatively correlated with river flow. The phycoperiphyton assemblage exhibited more direct responses in its density and richness to the hydrological changes (r(2) = 0.743 and 0.800, respectively). In functional terms, the El Nino phenomenon was defined by a greater abundance of omnivorous and insectivorous fishes, as well as filter feeders, scrapers and macroinvertebrate predators. During La Nina, a greater abundance of benthic fishes (both detritivorous and insectivorous) and shredder and collector-gatherer macroinvertebrates was observed. Differentiated responses recorded in the community were based on adaptive strategies for the local hydrological regime that enable fast recovery under conditions such as ENSO phenomena. Composition changes according to adaptations to different hydrological scenarios and the predominance of generalists' trophic guilds and species with plasticity in their habits and their ranges of environmental tolerance were found, supporting the habitat templet model. PMID- 26864788 TI - Expansion of a SNaPshot assay to a 55-SNP multiplex: Assay enhancements, validation, and power in forensic science. AB - A previously developed multiplex assay with 44 individual identification SNPs was expanded to a 55plex assay. Fifty-four highly informative SNPs and an amelogenin sex marker were amplified in one PCR reaction and then detected with two SNaPshot reactions using CE. PCR primers for four loci, 28 single-base extension primers, and the reaction conditions were altered to improve the robustness of the method. A detailed approach for allele calling was developed to guide analysis of the electropherogram. One hundred and eighty unrelated individuals and 100 father child-mother trios of the Han population in Hebei, China were analyzed. No mutation was found in the SNP loci. The combined mean match probability and cumulative probability of exclusion were 1.327 * 10(-22) and 0.999932, respectively. Analysis of the 54 SNPs and 26 STRs (included in the AmpFLSTR Identifiler and Investigator HDplex kits) showed no significant linkage disequilibriums. Our research shows that the expanded SNP multiplex assay is an easily performed and valuable method to supplement STR analysis. PMID- 26864789 TI - Use of the FLOTAC technique to diagnosing parasites of the urinary tract of dogs. AB - Among the nematodes that infect the urinary tract of dogs, the Dioctophyma renale and Capillaria plica are those more frequently reported. For a long time, sedimentation was the only method used to detect eggs of these parasites in urine. The aim of this study was to analyze urine samples (n = 54) of dogs, obtained by bladder catheterization or cystocentesis, by using a modified FLOTAC technique. Animals were divided into two groups, i.e., with (n = 20) and without (n = 34) suspicion of urinary disease. The overall positivity herein observed was 3.8 % (2/54), being all animals (10 %; 2/20) from the group with suspicion of urinary disease. In the first positive sample, a single egg of D. renale was detected, whereas in the second sample two trematode-like eggs were observed. This is the first short survey employed to detect eggs of parasites that inhabit the urinary tract of dogs using a modified FLOTAC technique; in addition, for the first time, eggs of D. renale have been detected using this tool. PMID- 26864790 TI - Identification of repellent odorants to the body louse, Pediculus humanus corporis, in clove essential oil. AB - The control of body lice is an important issue for human health and welfare because lice act as vectors of disease such as typhus, relapsing fever, and trench fever. Body lice exhibit avoidance behavior to some essential oils, including clove essential oil. Therefore, odorants containing clove essential oil components may potentially be useful in the development of repellents to body lice. However, such odorants that induce avoidance behavior in body lice have not yet been identified from clove essential oil. Here, we established an analysis method to evaluate the avoidance behavior of body lice to specific odorants. The behavioral analysis of the body lice in response to clove essential oil and its constituents revealed that eugenol, a major component of clove essential oil, has strong repellent effect on body lice, whereas the other components failed to induce obvious avoidance behavior. A comparison of the repellent effects of eugenol with those of other structurally related odorants revealed possible moieties that are important for the avoidance effects to body lice. The repellent effect of eugenol to body lice was enhanced by combining it with the other major component of clove essential oil, beta-caryophyllene. We conclude that a synthetic blend of eugenol and beta-caryophyllene is the most effective repellent to body lice. This finding will be valuable as the potential use of eugenol as body lice repellent. PMID- 26864791 TI - Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides. AB - A method to facilitate the characterization of stapled or cyclic peptides is reported via an arginine-selective derivatization strategy coupled with MS/MS analysis. Arginine residues are converted to ornithine residues through a deguanidination reaction that installs a highly selectively cleavable site in peptides. Upon activation by CID or UVPD, the ornithine residue cyclizes to promote cleavage of the adjacent amide bond. This Arg-specific process offers a unique strategy for site-selective ring opening of stapled and cyclic peptides. Upon activation of each derivatized peptide, site-specific backbone cleavage at the ornithine residue results in two complementary products: the lactam ring containing portion of the peptide and the amine-containing portion. The deguanidination process not only provides a specific marker site that initiates fragmentation of the peptide but also offers a means to unlock the staple and differentiate isobaric stapled peptides. PMID- 26864792 TI - Negative Ion In-Source Decay Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Sequencing Acidic Peptides. AB - Matrix-assisted laser desorption/ionization (MALDI) in-source decay was studied in the negative ion mode on deprotonated peptides to determine its usefulness for obtaining extensive sequence information for acidic peptides. Eight biological acidic peptides, ranging in size from 11 to 33 residues, were studied by negative ion mode ISD (nISD). The matrices 2,5-dihydroxybenzoic acid, 2-aminobenzoic acid, 2-aminobenzamide, 1,5-diaminonaphthalene, 5-amino-1-naphthol, 3-aminoquinoline, and 9-aminoacridine were used with each peptide. Optimal fragmentation was produced with 1,5-diaminonphthalene (DAN), and extensive sequence informative fragmentation was observed for every peptide except hirudin(54-65). Cleavage at the N-Calpha bond of the peptide backbone, producing c' and z' ions, was dominant for all peptides. Cleavage of the N-Calpha bond N-terminal to proline residues was not observed. The formation of c and z ions is also found in electron transfer dissociation (ETD), electron capture dissociation (ECD), and positive ion mode ISD, which are considered to be radical-driven techniques. Oxidized insulin chain A, which has four highly acidic oxidized cysteine residues, had less extensive fragmentation. This peptide also exhibited the only charged localized fragmentation, with more pronounced product ion formation adjacent to the highly acidic residues. In addition, spectra were obtained by positive ion mode ISD for each protonated peptide; more sequence informative fragmentation was observed via nISD for all peptides. Three of the peptides studied had no product ion formation in ISD, but extensive sequence informative fragmentation was found in their nISD spectra. The results of this study indicate that nISD can be used to readily obtain sequence information for acidic peptides. PMID- 26864793 TI - Fundamentals of Trapped Ion Mobility Spectrometry Part II: Fluid Dynamics. AB - Trapped ion mobility spectrometry (TIMS) is a new high resolution (R up to ~300) separation technique that utilizes an electric field to hold ions stationary against a moving gas. Recently, an analytical model for TIMS was derived and, in part, experimentally verified. A central, but not yet fully explored, component of the model involves the fluid dynamics at work. The present study characterizes the fluid dynamics in TIMS using simulations and ion mobility experiments. Results indicate that subsonic laminar flow develops in the analyzer, with pressure-dependent gas velocities between ~120 and 170 m/s measured at the position of ion elution. One of the key philosophical questions addressed is: how can mobility be measured in a dynamic system wherein the gas is expanding and its velocity is changing? We noted previously that the analytically useful work is primarily done on ions as they traverse the electric field gradient plateau in the analyzer. In the present work, we show that the position-dependent change in gas velocity on the plateau is balanced by a change in pressure and temperature, ultimately resulting in near position-independent drag force. That the drag force, and related variables, are nearly constant allows for the use of relatively simple equations to describe TIMS behavior. Nonetheless, we derive a more comprehensive model, which accounts for the spatial dependence of the flow variables. Experimental resolving power trends were found to be in close agreement with the theoretical dependence of the drag force, thus validating another principal component of TIMS theory. PMID- 26864794 TI - Strenuous exercise induces a hyperreactive rebalanced haemostatic state that is more pronounced in men. AB - Physical exercise is recommended for a healthy lifestyle. Strenuous exercise, however, may trigger the haemostatic system, increasing the risk of vascular thrombotic events and the incidence of primary cardiac arrest. Our goal was to study the effects of strenuous exercise on risk factors of cardiovascular disease. Blood was collected from 92 healthy volunteers who participated in the amateur version of the pro-tour Amstel Gold cycling race, before and directly after the race. Thrombin generation showed a shortening of the lag time and time to peak and an increase of the velocity index. Interestingly, the endogenous thrombin potential measured in plasma decreased due to reduced prothrombin conversion. Platelet reactivity increased and this effect was stronger in men than in women. Lower fibrinogen and higher D-dimer levels after exercise indicated higher fibrin formation. On the other hand, fibrinolysis was also elevated as indicated by a shortening of the clot lysis time. Exercise activated the endothelium (von Willebrand factor (VWF) and active VWF levels were elevated) and the immune system (concentrations IL-6, IL-8, MCP-1, RANTES and PDGF increased). Additionally, an increased cardiac troponin T level was measured post exercise. Strenuous exercise induces a temporary hyperreactive state in the body with enhanced pro- and anticoagulant responses. As strenuous exercise has a more pronounced effect on platelet function in male subjects, this gives a possible explanation for the higher incidence of sudden cardiac death during exercise compared to women. This trial is registered at www.clinicaltrials.gov as NCT02048462. PMID- 26864795 TI - Protective role of silent information regulator 1 against hepatic ischemia: effects on oxidative stress injury, inflammatory response, and MAPKs. AB - OBJECTIVE: Previous studies have verified that silent information regulator 1 (SIRT1), a class III histone deacetylase, protects against ischemia reperfusion (IR) injury (IRI) in some organs. In this study, we examined whether SIRT1 could protect against hepatic IRI and explored the potential mechanisms. RESEARCH DESIGN AND METHODS: We examined whether SIRT1 could protect against hepatic IRI in vivo and in vitro using hepatic-specific SIRT1(-/-) mice, SIRT1 siRNA transfected hepatocytes and SIRT1(+/+) hepatocytes. RESULTS: The expression and activity of SIRT1 were significantly reduced during reperfusion compared with that observed in the control group. Hepatic-specific SIRT1(-/-) mice exhibited significant increase of hepatic damage markers and augment of oxidative stress and inflammatory response compared with control mice. In vitro studies demonstrated similar results. Furthermore, SIRT1 upregulation protects against hepatic IRI, through the overexpression of p-JNK, p-p38MAPK, and p-ERK. The protection of SIRT1 can be effectively reversed by the inhibitors of p38MAPK, JNK, and ERK. CONCLUSION: The activation of SIRT1 significantly inhibits the oxidative stress and inflammatory response during hepatic IRI, which can be developed as a novel method to protect against hepatic IRI. PMID- 26864796 TI - Insertion Reactions of Neutral Phosphidozirconocene Complexes as a Convenient Entry into Frustrated Lewis Pair Territory. AB - Neutral phosphidozirconocene complexes [Cp2Zr(PR2)Me] (Cp=cyclopentadienyl; 1a: R=cyclohexyl (Cy); 1b: R=mesityl (Mes); 1c: R=tBu) undergo insertion into the Zr P bond by non-enolisable carbonyl building blocks (O=CR'R''), such as benzophenone, aldehydes, paraformaldehyde or CO2, to give [Cp2Zr(OCR'R''PR2)Me] (3-7). Depending on the steric bulk around P, complexes 3-7 react with B(C6F5)3 to give O-bridged cationic zirconocene dimers that display typical frustrated Lewis pair (FLP)/ambiphilic ligand behaviour. Thus, the reaction of {[Cp2Zr(MU OCHPhPCy2)][MeB(C6F5)3]}2 (10a) with chalcone results in 1,4 addition of the Zr(+)/P FLP, whereas the reaction of {[Cp2Zr(MU-OCHFcPCy2)][MeB(C6F5)3]}2 (11a; Fc=(C5H4)CpFe) with [Pd(eta(3)C3H5)Cl]2 yields the unique Zr-Fe-Pd trimetallic complex 13a, which has been characterised by XRD analysis. PMID- 26864797 TI - Pollinator-mediated assemblage processes in California wildflowers. AB - Community assembly is the result of multiple ecological and evolutionary forces that influence species coexistence. For flowering plants, pollinators are often essential for plant reproduction and establishment, and pollinator-mediated interactions may influence plant community composition. Here, we use null models and community phylogenetic analyses of co-occurrence patterns to determine the role of pollinator-mediated processes in structuring plant communities dominated by congeners. We surveyed three species-rich genera (Limnanthes, Mimulus and Clarkia) with centres of diversity in the Sierra Nevada of California. Each genus contains species that co-flower and share pollinators, and each has a robust phylogeny. Within each genus, we surveyed 44-48 communities at three spatial scales, measured floral and vegetative traits and tested for segregation or aggregation of: (i) species, (ii) floral traits (which are likely to be influenced by pollinators), and (iii) vegetative traits (which are likely affected by other environmental factors). We detected both aggregation and segregation of floral traits that were uncorrelated with vegetative trait patterns; we infer that pollinators have shaped the community assembly although the mechanisms may be varied (competition, facilitation, or filtering). We also found that mating system differences may play an important role in allowing species co-occurrence. Together, it appears that pollinators influence community assemblage in these three clades. PMID- 26864798 TI - Explaining the geographic spread of emerging epidemics: a framework for comparing viral phylogenies and environmental landscape data. AB - BACKGROUND: Phylogenetic analysis is now an important tool in the study of viral outbreaks. It can reconstruct epidemic history when surveillance epidemiology data are sparse, and can indicate transmission linkages among infections that may not otherwise be evident. However, a remaining challenge is to develop an analytical framework that can test hypotheses about the effect of environmental variables on pathogen spatial spread. Recent phylogeographic approaches can reconstruct the history of virus dispersal from sampled viral genomes and infer the locations of ancestral infections. Such methods provide a unique source of spatio-temporal information, and are exploited here. RESULTS: We present and apply a new statistical framework that combines genomic and geographic data to test the impact of environmental variables on the mode and tempo of pathogen dispersal during emerging epidemics. First, the spatial history of an emerging pathogen is estimated using standard phylogeographic methods. The inferred dispersal path for each phylogenetic lineage is then assigned a "weight" using environmental data (e.g. altitude, land cover). Next, tests measure the association between each environmental variable and lineage movement. A randomisation procedure is used to assess statistical confidence and we validate this approach using simulated data. We apply our new framework to a set of gene sequences from an epidemic of rabies virus in North American raccoons. We test the impact of six different environmental variables on this epidemic and demonstrate that elevation is associated with a slower rabies spread in a natural population. CONCLUSION: This study shows that it is possible to integrate genomic and environmental data in order to test hypotheses concerning the mode and tempo of virus dispersal during emerging epidemics. PMID- 26864799 TI - Functional and structural characterization of domain truncated violaxanthin de epoxidase. AB - Photosynthetic organisms need protection against excessive light. By using non photochemical quenching, where the excess light is converted into heat, the organism can survive at higher light intensities. This process is partly initiated by the formation of zeaxanthin, which is achieved by the de-epoxidation of violaxanthin and antheraxanthin to zeaxanthin. This reaction is catalyzed by violaxanthin de-epoxidase (VDE). VDE consists of three domains of which the central lipocalin-like domain has been the most characterized. By truncating the domains surrounding the lipocalin-like domain, we show that VDE activity is possible without the C-terminal domain but not without the N-terminal domain. The N-terminal domain shows no VDE activity by itself but when separately expressed domains are mixed, VDE activity is possible. This shows that these domains can be folded separately and could therefore be studied separately. An increase of the hydrodynamic radius of wild-type VDE was observed when pH was lowered toward the pH required for activity, consistent with a pH-dependent oligomerization. The C terminally truncated VDE did not show such an oligomerization, was relatively more active at higher pH but did not alter the KM for ascorbate. Circular dichroism measurements revealed the presence of alpha-helical structure in both the N- and C-terminal domains. By measuring the initial formation of the product, VDE was found to convert a large number of violaxanthin molecules to antheraxanthin before producing any zeaxanthin, favoring a model where violaxanthin is bound non-symmetrically in VDE. PMID- 26864800 TI - Cross-resistance to prosulfocarb + S-metolachlor and pyroxasulfone selected by either herbicide in Lolium rigidum. AB - BACKGROUND: Weeds can be a greater constraint to crop production than animal pests and pathogens. Pre-emergence herbicides are crucial in many cropping systems to control weeds that have evolved resistance to selective post-emergence herbicides. In this study we assessed the potential to evolve resistance to the pre-emergence herbicides prosulfocarb + S-metolachlor or pyroxasulfone in 50 individual field Lolium rigidum populations collected in a random survey in Western Australia prior to commercialisation of these pre-emergence herbicides. RESULTS: This study shows for the first time that in randomly collected L. rigidum field populations the selection with either prosulfocarb + S-metolachlor or pyroxasulfone can result in concomitant evolution of resistance to both prosulfocarb + S-metolachlor and pyroxasulfone after three generations. CONCLUSIONS: In the major weed L. rigidum, traits conferring resistance to new herbicides can be present before herbicide commercialisation. Proactive and multidisciplinary research (evolutionary ecology, modelling and molecular biology) is required to detect and analyse resistant populations before they can appear in the field. Several studies show that evolved cross-resistance in weeds is complex and often unpredictable. Thus, long-term management of cross-resistant weeds must be achieved through heterogeneity of selection by effective chemical, cultural and physical weed control strategies that can delay herbicide resistance evolution. (c) 2016 Society of Chemical Industry. PMID- 26864801 TI - Advantages of magnifying narrow-band imaging for diagnosing colorectal cancer coexisting with sessile serrated adenoma/polyp. AB - BACKGROUND AND AIM: In the present study, we investigated the advantages of narrow-band imaging (NBI) for efficient diagnosis of sessile serrated adenoma/polyp (SSA/P). The main objective of this study was to analyze the characteristic features of cancer coexisting with serrated lesion by carrying out NBI. METHODS: We evaluated 264 non-malignant serrated lesions by using three modalities (conventional white light colonoscopy, magnifying chromoendoscopy, and magnifying NBI). Of the evaluated cancer cases with serrated lesions, 37 fulfilled the inclusion criteria. RESULTS: In diagnosing non-malignant SSA/P, an expanded crypt opening (ECO) under magnifying NBI is a useful sign. One hundred and twenty-five lesions (87%) of observed ECO were, at the same time, detected to have type II open pit pattern, which is known to be a valuable indicator when using magnifying chromoendoscopy. ECO had high sensitivity of 80% for identifying SSA/P, with 62% specificity and 83% positive predictive value (PPV). In detecting the cancer with SSA/P, irregular vessels under magnifying NBI were frequently observed with 100% sensitivity and 99% specificity, 86% PPV and 100% negative predictive value. CONCLUSIONS: A focus on irregular vessels in serrated lesions might be useful for identification of cancer with SSA/P. This is an advantage of carrying out magnifying NBI in addition to being used simultaneously with other modalities by switching, and observations can be made by using wash-in water alone. We can carry out advanced examinations for selected lesions with irregular vessels. To confirm cancerous demarcation and invasion depth, a combination of all three aforementioned modalities should be done. PMID- 26864803 TI - Effect of a Clostridium difficile Infection Prevention Initiative in Veterans Affairs Acute Care Facilities. AB - Rates of clinically confirmed hospital-onset healthcare facility-associated Clostridium difficile infections from July 1, 2012, through March 31, 2015, in 127 acute care Veterans Affairs facilities were evaluated. Quarterly pooled national standardized infection ratios decreased 15% from baseline by the final quarter of the analysis period (P=.01, linear regression). Infect Control Hosp Epidemiol 2016;37:720-722. PMID- 26864802 TI - Is increased hepatitis C virus case-finding combined with current or 8-week to 12 week direct-acting antiviral therapy cost-effective in UK prisons? A prevention benefit analysis. AB - Prisoners have a high prevalence of hepatitis C virus (HCV), but case-finding may not have been cost-effective because treatment often exceeded average prison stay combined with a lack of continuity of care. We assessed the cost-effectiveness of increased HCV case-finding and treatment in UK prisons using short-course therapies. A dynamic HCV transmission model assesses the cost-effectiveness of doubling HCV case-finding (achieved through introducing opt-out HCV testing in UK pilot prisons) and increasing treatment in UK prisons compared to status quo voluntary risk-based testing (6% prison entrants/year), using currently recommended therapies (8-24 weeks) or interferon (IFN)-free direct-acting antivirals (DAAs; 8-12 weeks, 95% sustained virological response, L3300/week). Costs (British pounds, L) and health utilities (quality-adjusted life years) were used to calculate mean incremental cost-effectiveness ratios (ICERs). We assumed 56% referral and 2.5%/25% of referred people who inject drugs (PWID)/ex-PWID treated within 2 months of diagnosis in prison. PWID and ex-PWID or non-PWID are in prison an average 4 and 8 months, respectively. Doubling prison testing rates with existing treatments produces a mean ICER of L19,850/quality-adjusted life years gained compared to current testing/treatment and is 45% likely to be cost effective under a L20,000 willingness-to-pay threshold. Switching to 8-week to 12 week IFN-free DAAs in prisons could increase cost-effectiveness (ICER L15,090/quality-adjusted life years gained). Excluding prevention benefit decreases cost-effectiveness. If >10% referred PWID are treated in prison (2.5% base case), either treatment could be highly cost-effective (ICER= 2 more early than serum creatinine and urine output, using the respective Kidney Disease | Improving Global Outcomes (KDIGO) criteria for definition and classification of AKI, and compare this to urinary neutrophil gelatinase associated lipocalin (UNGAL). METHODS: This was a translational single-center, prospective cohort study at the 22-bed surgical and 14-bed medical intensive care units (ICU) of Ghent University Hospital. We enrolled 181 severely ill adult patients who did not yet have AKI stage >= 2 based on the KDIGO criteria at time of enrollment. The concentration of creatinine (serum, urine) and CHI3L1 (serum, urine) was measured at least daily, and urine output hourly, in the period from enrollment till ICU discharge with a maximum of 7 ICU-days. The concentration of UNGAL was measured at enrollment. The primary endpoint was the development of AKI stage >= 2 within 12 h after enrollment. RESULTS: After enrollment, 21 (12%) patients developed AKI stage >= 2 within the next 7 days, with 6 (3%) of them reaching this condition within the first 12 h. The enrollment concentration of UCHI3L1 predicted the occurrence of AKI stage >= 2 within the next 12 h with a good AUC-ROC of 0.792 (95% CI: 0.726-0.849). This performance was similar to that of UNGAL (AUC-ROC of 0.748 (95% CI: 0.678-0.810)). Also, the samples collected in the 24-h time frame preceding diagnosis of the 1(st) episode of AKI stage >= 2 had a 2.0 times higher (95% CI: 1.3-3.1) estimated marginal mean of UCHI3L1 than controls. We further found that increasing UCHI3L1 concentrations were associated with increasing AKI severity. CONCLUSIONS: In this pilot study we found that UCHI3L1 was a good biomarker for prediction of AKI stage >= 2 in adult ICU patients. PMID- 26864839 TI - Exploring the Lived Experience of Difficult Sleep and Good Sleep Among Psychiatric Inpatients. AB - The purpose of this qualitative study was to explore psychiatric inpatients' reflections on their experiences with sleep throughout their lives. Fourteen patients in an acute care behavioral health unit agreed to participate in this study. Participants met individually with a researcher to reflect on times in their lives when they experienced good sleep; times when they had difficulty sleeping; and times when difficult sleep was resolved. The major findings of the study indicated that feeling alone with life problems triggered difficult sleep; while feelings of belonging and purpose were associated with good sleep. PMID- 26864840 TI - Being a Parent to a Young Adult with Mental Illness in Transition to Adulthood. AB - Parents of young adults with mental illness may face a continued demand for support, even though their children have reached the age of majority. The aim of this study was to explore relatives' experiences of parenting a young adult with mental illness in transition to adulthood. Individual interviews were conducted and analysed according to Grounded Theory. The results showed that relatives experienced powerlessness and a sense of inescapable duty with limited possibilities to be relieved. With a family nursing approach, relatives can be supported and, when the young adults' needs of care are met, they can be relieved from their burden of responsibility. PMID- 26864841 TI - Depression and Diabetes in a Primarily African American Female Population. AB - Depression is one of the most serious mental health comorbidities associated with diabetes. In this pilot study, we describe the associations identified via a cross-sectional survey among demographic variables, depression, self-efficacy, and glycemic control in a primarily minority population (mean age = 57.9 years; n = 30) with diabetes mellitus. Descriptive, bivariate, and correlation analyses were conducted. A significant inverse relationship was detected between depression and self-efficacy; however the relationship between depression and A1C was not significant. The implications of these findings include the need for interventions that regularly screen for depression and self-efficacy in persons diagnosed with diabetes mellitus, especially in the earlier years of diagnosis. PMID- 26864842 TI - Experiences of Older Men Living Alone: A Qualitative Study. AB - More and more old people live alone, and living alone is reported to be a key risk factor for experiencing loneliness and developing poor health. The purpose of this qualitative study was to explore the experiences of living alone for older men. Systematic text condensation and hermeneutic interpretation were used in analysis of the data. Four themes emerged: lonely at times, missing and longing for a shared life, keeping active, and some kind of freedom. The findings revealed that inner and outer resources come into play and have influence on the processes of managing and solving the situation of living alone. The findings are in accordance with theoretical perspectives on loneliness, aloneness, and solitude. The findings offer nurses in any clinical context valuable information to allow them to address the core emotional and potential mental health issues old men face in coping with the situation of living alone. PMID- 26864843 TI - Culture Change? A Secular Shift. PMID- 26864844 TI - Diagnostic Sedition: Re-Considering the Ascension and Hegemony of Contemporary Psychiatric Diagnosis. PMID- 26864845 TI - Non-Specialist Health Worker Interventions for the Care of Mental, Neurological, and Substance-Abuse Disorders in Low- and Middle-Income Countries. PMID- 26864848 TI - The Perils of Integrating Wellness and Safety and Health and the Possibility of a Worker-Oriented Alternative. AB - Integration of workplace wellness with safety and health has gained momentum on the initiative of the state allied with a segment of large employers and some health and safety professionals. Integration has a dual potential: to fundamentally reshape occupational health in ways that profoundly benefit workers, or to serve neoliberal corporate goals. A focus on the workplace and the ways work and health interact broaden the definition of a work-related injury or illness and emphasize and challenge the employer decisions that create hazards and determine risk. However, the implementation of integration is taking place in a context of corporate dominance and the aggressive pursuit of a neoliberal agenda. Consequently, in practice, integration efforts have emphasized individual worker responsibility for health and fail to actually integrate wellness with safety and health in a meaningful way. Can an alternative be envisioned and pursued that realizes the promise of integration for workers? PMID- 26864852 TI - Understanding the Ureter: Challenges and Opportunities. AB - The ureter is possibly the least studied and most poorly understood organ of the urinary tract. The pathophysiologic basis underlying the use of alpha-blockers to improve ureteral stone passage or to treat ureteral stent symptoms is poorly understood. This, in part, may explain why clinical studies of medical expulsive therapy for ureteral stone passage are fraught with conflicting data. Methods to study human ureter in vivo are few and challenging. The findings of many of the ureteral studies are from observational in vitro studies and were evaluated in other animal species that may not be applicable in human beings. There are few mechanistic studies evaluating the underlying molecular pathophysiologic mechanisms of human ureter. This is critical to our understanding and treatment of stent symptoms, including the development of a patient friendly ureteral stent and for the pharmacologic modulation of ureteral activity. The following is an overview of some of the observational and mechanistic ureteral studies evaluating the pharmacologic and stent effects, including potential areas for further research. PMID- 26864853 TI - Is deep neuromuscular blockade beneficial in laparoscopic surgery? Yes, probably. AB - BACKGROUND: Deep neuromuscular blockade during laparoscopic surgery may provide some clinical benefit. We present the 'Pro-' argument in this paired position paper. METHODS: We reviewed recent evidence from a basic database of references which we agreed on with the 'Con-' side, and present this in narrative form. We have shared our analysis and text with the authors of the 'Con-' side of these paired position papers during the preparation of the manuscripts. RESULTS: There are a few low risk of bias studies indicating that use of deep neuromuscular blockade improve surgical conditions and improve patient outcomes such as post operative pain in laparoscopic surgery. CONCLUSION: Our interpretation of recent findings is that there is reason to believe that there may be some patient benefit of deep neuromuscular blockade in this context, and more detailed study is needed. PMID- 26864851 TI - A randomised controlled trial of a lifestyle behavioural intervention for patients with low back pain, who are overweight or obese: study protocol. AB - BACKGROUND: Low back pain is a highly prevalent condition with a significant global burden. Management of lifestyle factors such as overweight and obesity may improve low back pain patient outcomes. Currently there are no randomised controlled trials that have been conducted to assess the effectiveness of lifestyle behavioural interventions in managing low back pain. The aim of this trial is to determine if a telephone-based lifestyle behavioural intervention is effective in reducing pain intensity in overweight or obese patients with low back pain, compared to usual care. METHODS/DESIGN: A randomised controlled trial will be conducted with patients waiting for an outpatient consultation with an orthopaedic surgeon at a public tertiary referral hospital within New South Wales, Australia for chronic low back pain. Patients will be randomly allocated in a 1:1 ratio to receive a lifestyle behavioural intervention (intervention group) or continue with usual care (control group). After baseline data collection, patients in the intervention group will receive a clinical consultation followed by a 6-month telephone-based lifestyle behavioural intervention (10 individually tailored sessions over a 6-month period) and patients in the control group will continue with usual care. Participants will be followed for 26 weeks and asked to undertake three self-reported questionnaires at baseline (pre-randomisation), week 6 and 26 post randomisation to collect primary and secondary outcome data. The study requires a sample of 80 participants per group to detect a 1.5 point difference in pain intensity (primary outcome) 26 weeks post randomisation. The primary outcome, pain intensity, will be measured using a 0-10 numerical rating scale. DISCUSSION: The study will provide robust evidence regarding the effectiveness of a lifestyle behavioural intervention in reducing pain intensity in overweight or obese patients with low back pain and inform management of these patients. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12615000478516 , Registered 14/05/2015. PMID- 26864854 TI - Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors. AB - Air pollution is implicated in neurodegenerative disease risk and progression and in microglial activation, but the mechanisms are unknown. In this study, microglia remained activated 24 h after ozone (O3) exposure in rats, suggesting a persistent signal from lung to brain. Ex vivo analysis of serum from O3-treated rats revealed an augmented microglial proinflammatory response and beta-amyloid 42 (Abeta42) neurotoxicity independent of traditional circulating cytokines, where macrophage-1 antigen-mediated microglia proinflammatory priming. Aged mice exhibited reduced pulmonary immune profiles and the most pronounced neuroinflammation and microglial activation in response to mixed vehicle emissions. Consistent with this premise, cluster of differentiation 36 (CD36)(-/ ) mice exhibited impaired pulmonary immune responses concurrent with augmented neuroinflammation and microglial activation in response to O3 Further, aging glia were more sensitive to the proinflammatory effects of O3 serum. Together, these findings outline the lung-brain axis, where air pollutant exposures result in circulating, cytokine-independent signals present in serum that elevate the brain proinflammatory milieu, which is linked to the pulmonary response and is further augmented with age.-Mumaw, C. L., Levesque, S., McGraw, C., Robertson, S., Lucas, S., Stafflinger, J. E., Campen, M. J., Hall, P., Norenberg, J. P., Anderson, T., Lund, A. K., McDonald, J. D., Ottens, A. K., Block, M. L. Microglial priming through the lung-brain axis: the role of air pollution-induced circulating factors. PMID- 26864857 TI - Hydrophilic Domains Enhance Nanobubble Stability. AB - Highly stable nanoscale gas states at solid/liquid interfaces, referred to as nanobubbles, have been widely studied for over a decade. In this study, nanobubbles generated on a hydrophobic Teflon amorphous fluoroplastic thin film in the presence and absence of hydrophilic carbon domains are investigated by peak force quantitative nanomechanics. On the hydrophobic surface without hydrophilic domains, a small number of nanobubbles are generated and then rapidly decrease in size. On the hydrophobic surface with hydrophilic domains, the hydrophilic domains have a significant effect on the generation and stability of nanobubbles, with bubbles remaining on the surface for up to three days. PMID- 26864855 TI - The Alpha-defensin Test for Periprosthetic Joint Infections Is Not Affected by Prior Antibiotic Administration. AB - BACKGROUND: Previous studies have demonstrated that the administration of antibiotics to patients before performing diagnostic testing for periprosthetic joint infection (PJI) can interfere with the accuracy of test results. Although a single-institution study has suggested that alpha-defensin maintains its concentration and sensitivity even after antibiotic treatment, this has not yet been demonstrated in a larger multiinstitutional study. QUESTIONS/PURPOSES: (1) For the evaluation of PJI, is prior antibiotic administration associated with decreased alpha-defensin levels? (2) When prior antibiotics are given, is alpha defensin a better screening test for PJI than the traditional tests (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], fluid white blood cells, fluid polymorphonuclear cells [PMNs], and fluid culture)? METHODS: This retrospective study included data from 106 hip and knee arthroplasties with Musculoskeletal Infection Society-defined PJI from four centers. Of the 106 patients in this study, 30 (28%) were treated with antibiotics for PJI before diagnostic workup (ABX group), and 76 (72%) were not treated before the diagnostic workup (NO-ABX group). There were no differences in age, sex, joint, culture-negative rate, or bacteriology between groups. The patients in the ABX group had antibiotics initiated by physicians who commenced care before assessment for PJI by the treating surgeon's service. We compared the alpha defensin levels and sensitivity between the ABX and NO-ABX groups. Additionally, the sensitivity of the alpha-defensin test was compared to that of traditional tests for PJI among patients on antibiotics. RESULTS: The administration of antibiotics before performing the alpha-defensin test for PJI was not associated with a decreased median alpha-defensin level (ABX group, median 4.2 [range, 1.79 12.8 S/CO] versus NO-ABX, median 4.9 [range, 0.5-16.8 S/CO], difference of medians: 0.68 S/CO [95% confidence interval {CI}, -0.98 to 1.26], p = 0.451). Furthermore, the alpha-defensin test had a higher sensitivity (100%; 95% CI, 88.4%-100.0%) in diagnosing PJI among patients on antibiotics when compared with the ESR (69.0% [95% CI, 49.17%-84.72%], p = 0.001), the CRP (79.3% [95% CI, 60.3% 92.0%], p = 0.009), the fluid PMN% (79.3% [95% CI, 60.3%-92.0%), p = 0.009), and fluid culture (70.0% [95% CI, 50.6%-85.3%], p = 0.001). CONCLUSIONS: The alpha defensin test maintains its concentration and sensitivity for PJI even in the setting of antibiotic administration. Furthermore, among patients with PJI on antibiotics, the alpha-defensin tests demonstrated a higher sensitivity in detecting PJI when compared with the ESR, CRP, fluid PMN%, and fluid culture. The high sensitivity of the alpha-defensin test, even in the setting of prior antibiotic treatment, provides excellent utility as a screening test for PJI. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 26864856 TI - A genome-wide search for epigenetically [corrected] regulated genes in zebra finch using MethylCap-seq and RNA-seq. AB - Learning and memory formation are known to require dynamic CpG (de)methylation and gene expression changes. Here, we aimed at establishing a genome-wide DNA methylation map of the zebra finch genome, a model organism in neuroscience, as well as identifying putatively epigenetically regulated genes. RNA- and MethylCap seq experiments were performed on two zebra finch cell lines in presence or absence of 5-aza-2'-deoxycytidine induced demethylation. First, the MethylCap-seq methodology was validated in zebra finch by comparison with RRBS-generated data. To assess the influence of (variable) methylation on gene expression, RNA-seq experiments were performed as well. Comparison of RNA-seq and MethylCap-seq results showed that at least 357 of the 3,457 AZA-upregulated genes are putatively regulated by methylation in the promoter region, for which a pathway analysis showed remarkable enrichment for neurological networks. A subset of genes was validated using Exon Arrays, quantitative RT-PCR and CpG pyrosequencing on bisulfite-treated samples. To our knowledge, this study provides the first genome-wide DNA methylation map of the zebra finch genome as well as a comprehensive set of genes of which transcription is under putative methylation control. PMID- 26864858 TI - Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods. AB - PURPOSE: Evaluation of particle size distribution (PSD) of multimodal dispersion of nanoparticles is a difficult task due to inherent limitations of size measurement methods. The present work reports the evaluation of PSD of a dispersion of poly(isobutylcyanoacrylate) nanoparticles decorated with dextran known as multimodal and developed as nanomedecine. METHODS: The nine methods used were classified as batch particle i.e. Static Light Scattering (SLS) and Dynamic Light Scattering (DLS), single particle i.e. Electron Microscopy (EM), Atomic Force Microscopy (AFM), Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle Tracking Analysis (NTA) and separative particle i.e. Asymmetrical Flow Field-Flow Fractionation coupled with DLS (AsFlFFF) size measurement methods. RESULTS: The multimodal dispersion was identified using AFM, TRPS and NTA and results were consistent with those provided with the method based on a separation step prior to on-line size measurements. None of the light scattering batch methods could reveal the complexity of the PSD of the dispersion. CONCLUSIONS: Difference between PSD obtained from all size measurement methods tested suggested that study of the PSD of multimodal dispersion required to analyze samples by at least one of the single size particle measurement method or a method that uses a separation step prior PSD measurement. PMID- 26864861 TI - Counter-ion distribution around flexible polyelectrolytes having different molecular architecture. AB - We explore the monovalent counter-ion distribution around flexible highly-charged polyelectrolytes with different molecular architectures (linear chains, stars, and unknotted and trefoil rings) using molecular dynamics simulations that include an explicit solvent that interacts with the polyelectrolyte. In particular, we find that the molecular topology influences the fraction of counter-ions transiently associating with the polyelectrolyte on a scale of the order of the chain segments, forming a "condensed" counter-ion interfacial layer. As with the hydrogen bonding of water to proteins and other polymers, the persistence time of these interfacial "bound" counter-ions is relatively short, O(1 ps), and we characterize the fluctuations in the number of the counter-ions populating the interfacial layer. We also find that the counter-ions are distributed in a non-uniform fashion on the polyelectrolyte backbone, forming dynamical clusters whose form and average size is sensitive to molecular architecture. In addition, we find that the residual bound counter-ions, not located in either the interfacial layer or the bulk solution, form a diffuse ionic cloud around the polyelectrolyte due to the uncompensated polyelectrolyte charge along the backbone. Generally charge valence strongly influences the extent of the diffuse counter-ion cloud, but in the case of monovalent counter ions, we find that the size of the diffuse counter-ion cloud nearly coincides with the polyelectrolyte radius of gyration, independent of molecular topology. PMID- 26864859 TI - Simultaneous resonant x-ray diffraction measurement of polarization inversion and lattice strain in polycrystalline ferroelectrics. AB - Structure-property relationships in ferroelectrics extend over several length scales from the individual unit cell to the macroscopic device, and with dynamics spanning a broad temporal domain. Characterizing the multi-scale structural origin of electric field-induced polarization reversal and strain in ferroelectrics is an ongoing challenge that so far has obscured its fundamental behaviour. By utilizing small intensity differences between Friedel pairs due to resonant scattering, we demonstrate a time-resolved X-ray diffraction technique for directly and simultaneously measuring both lattice strain and, for the first time, polarization reversal during in-situ electrical perturbation. This technique is demonstrated for BaTiO3-BiZn0.5Ti0.5O3 (BT-BZT) polycrystalline ferroelectrics, a prototypical lead-free piezoelectric with an ambiguous switching mechanism. This combines the benefits of spectroscopic and diffraction based measurements into a single and robust technique with time resolution down to the ns scale, opening a new door to in-situ structure-property characterization that probes the full extent of the ferroelectric behaviour. PMID- 26864862 TI - XELOX vs. FOLFOX in metastatic colorectal cancer: An updated meta-analysis. AB - This meta-analysis aims to evaluate chemotherapy with XELOX (capecitabine plus oxaliplatin) versus FOLFOX (fluorouracil plus oxaliplatin) as a treatment for metastatic colorectal cancer (mCRC) in terms of efficacy and safety. Only randomized controlled trials (RCTs) comparing XELOX versus FOLFOX were included. A total of 4,363 patients from eight RCTs were available for analysis. Pooled analysis revealed that there were no statistical differences between both arms in OS, and ORR. XELOX arm had a higher incidence of thrombocytopenia, hand-foot syndrome, and diarrhea, whereas neutropenia had a higher incidence in the FOLFOX group. For mCRC, the effect of XELOX is similar to FOLFOX. PMID- 26864863 TI - Antidepressants are addictive and increase the risk of relapse. PMID- 26864865 TI - Elevated interleukin-1beta in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis. AB - PURPOSE OF THE STUDY: To explore the relationship between IL-1beta expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). MATERIALS AND METHODS: qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1beta in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. RESULTS: Although no significant differences in IL-1beta levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1beta mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1beta mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1beta levels with the pathogenesis of HT. CONCLUSION: Our study suggests that IL-1beta may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment. PMID- 26864864 TI - Emerging roles for vascular smooth muscle cell exosomes in calcification and coagulation. AB - Vascular smooth muscle cell (VSMC) phenotypic conversion from a contractile to 'synthetic' state contributes to vascular pathologies including restenosis, atherosclerosis and vascular calcification. We have recently found that the secretion of exosomes is a feature of 'synthetic' VSMCs and that exosomes are novel players in vascular repair processes as well as pathological vascular thrombosis and calcification. Pro-inflammatory cytokines and growth factors as well as mineral imbalance stimulate exosome secretion by VSMCs, most likely by the activation of sphingomyelin phosphodiesterase 3 (SMPD3) and cytoskeletal remodelling. Calcium stress induces dramatic changes in VSMC exosome composition and accumulation of phosphatidylserine (PS), annexin A6 and matrix metalloproteinase-2, which converts exosomes into a nidus for calcification. In addition, by presenting PS, VSMC exosomes can also provide the catalytic surface for the activation of coagulation factors. Recent data showing that VSMC exosomes are loaded with proteins and miRNA regulating cell adhesion and migration highlight VSMC exosomes as potentially important communication messengers in vascular repair. Thus, the identification of signalling pathways regulating VSMC exosome secretion, including activation of SMPD3 and cytoskeletal rearrangements, opens up novel avenues for a deeper understanding of vascular remodelling processes. PMID- 26864867 TI - Development of an analytical method to quantify PBDEs, OH-BDEs, HBCDs, 2,4,6-TBP, EH-TBB, and BEH-TEBP in human serum. AB - Polybrominated diphenyl ethers (PBDEs) flame retardants (FRs) were phased-out in the mid-2000s (penta- and octaBDE) and 2013 (decaBDE); however, their hydroxylated metabolites (OH-BDEs) are still commonly detected in human serum. Today, novel FRs such as Firemaster(r) 550, a mixture that contains two brominated compounds, EH-TBB and BEH-TEBP are used as replacements for PBDEs in some applications, and there is a need to develop a comprehensive analytical method to assess exposure to both legacy PBDEs and novel FRs. This study developed a solid-phase extraction (SPE)-based method to analyze PBDEs, OH-BDEs, 2,4,6-tribromophenol (TBP), hexabromocylcododecane isomers (HBCDs), EH-TBB, and BEH-TEBP in human serum. Briefly, serum proteins were first denatured with formic acid, and then the target analytes were isolated using a SPE column. Finally, the extract was cleaned and fractioned using a silica SPE column. Method performance was assessed by spiking fetal bovine serum with 1-2 ng of the target analytes, and method accuracy was quantified by comparison to a serum Standard Reference Material (SRM). The developed method showed good recovery and accuracy for all target analytes with the exception of the very low and very high molecular weight PBDE congeners. Using this method, 43 serum samples collected from the Healthy Pregnancy, Healthy Baby Study (HPHB) cohort in Durham, NC, USA were analyzed for FRs. A novel finding was the ubiquitous detection of 2,4,6-TBP, at levels greater than the individual PBDE congeners. Furthermore, 2,4,6-TBP was positively correlated with PBDEs, suggesting that they may have a similar source of exposure, or that 2,4,6-TBP may result from metabolism of PBDEs in vivo. PMID- 26864869 TI - Novel Function of Serine Protease HTRA1 in Inhibiting Adipogenic Differentiation of Human Mesenchymal Stem Cells via MAP Kinase-Mediated MMP Upregulation. AB - Adipogenesis is the process by which mesenchymal stem cells (MSCs) develop into lipid-laden adipocytes. Being the dominant cell type within adipose tissue, adipocytes play a central role in regulating circulating fatty acid levels, which is considered to be of critical importance in maintaining insulin sensitivity. High temperature requirement protease A1 (HTRA1) is a newly recognized regulator of MSC differentiation, although its role as a mediator of adipogenesis has not yet been defined. The aim of this work was therefore to evaluate HTRA1's influence on human MSC (hMSC) adipogenesis and to establish a potential mode of action. We report that the addition of exogenous HTRA1 to hMSCs undergoing adipogenesis suppressed their ability to develop into lipid laden adipocytes. These effects were demonstrated as being reliant on both its protease and PDZ domain, and were mediated through the actions of c-Jun N-terminal kinase and matrix metalloproteinases (MMPs). The relevance of such findings with regards to HTRA1's potential influence on adipocyte function in vivo is made evident by the fact that HTRA1 and MMP-13 were readily identifiable within crown-like structures present in visceral adipose tissue samples from insulin resistant obese human subjects. These data therefore implicate HTRA1 as a negative regulator of MSC adipogenesis and are suggestive of its potential involvement in adipose tissue remodeling under pathological conditions. Stem Cells 2016;34:1601-1614. PMID- 26864868 TI - Potential diagnostic value of serum/pleural fluid IL-31 levels for tuberculous pleural effusion. AB - The aim of this study was to explore the diagnostic value of IL-31 levels in the pleural fluid and plasma to differentially diagnose tuberculous and malignant pleural effusion. We enrolled 91 cases, including tuberculous pleural effusion (TPE, n = 50), malignant pleural effusion (MPE, n = 41), other cases including pneumonia with pleural fluid, pulmonary tuberculosis and healthy people as controls. Whole blood was stimulated with the M. tuberculosis-specific antigens and plasma was collected. The multiplex bead-based cytokine immunoassay was employed to measure the levels of various cytokines. IL-31 was found to be the most prominent cytokine (P < 0.0001), and with an optimal cut-off value of 67.5 pg/mL, the sensitivity and specificity for the diagnosis of TPE were 86% and 100%, respectively. Furthermore, the tuberculosis-specific IL-31 levels in the plasma of TPE patients were higher than that of MPE patients (P = 0.0002). At an optimal cut-off value of 23.9 pg/mL, the sensitivity and specificity for the diagnosis of TPE were 92.9% and 85.7%, respectively. Ultimately, the combination of pleural fluid with the plasma tuberculosis-specific IL-31 levels improved the sensitivity and specificity to 94.0% and 95.1%, respectively. Thus, we identified a novel biomarker for the diagnosis of TPE for clinical application. PMID- 26864870 TI - Parental anxiety in childhood epilepsy: A systematic review. AB - The aim was to systematically review studies that have focused on symptoms of anxiety reported by parents of children (0-18 years) with epilepsy. PubMed was used to identify relevant studies. Selected studies were reviewed with respect to prevalence of above threshold scores and comparisons with controls on standardized measures of anxiety. Studies are also reported with respect to factors associated with parental anxiety, impact on child outcomes, and comparisons with studies that have included equivalent measures of symptoms of depression. Fifteen studies that met inclusion criteria were identified. None of the studies were population based. The percentage of parents scoring above cutoffs on standardized measures of anxiety was 9-58%. In comparison with parents of healthy controls, parents of children with epilepsy had higher mean scores in two of three studies where this was measured. Possible correlates of parental anxiety in childhood epilepsy that were considered varied widely across studies. Factors such as seizure frequency and use of antiepileptic drugs (AEDs) have been associated with parental anxiety in some but not all studies. With respect to child outcome, increased parental anxiety has been associated with lower quality of life and lower scores on adaptive behavior domains. Symptoms of anxiety are common among parents of children with epilepsy. There is a need for more systematic, representative studies to identify the prevalence of clinically significant anxiety and track the course of symptoms. Such studies will help to identify more clearly factors associated with parental anxiety and impact of symptoms on child and parent outcomes. Intervention studies are needed to evaluate approaches that target a reduction in symptoms and the potential impact on parental and child functioning. Furthermore, there is a need to evaluate the impact of antiepileptic therapies and interventions that focus on child neurobehavioral comorbidities on parental anxiety. PMID- 26864871 TI - Factorial Validity and Invariance Assessment of a Short Version of the Recalled Childhood Gender Identity/Role Questionnaire. AB - Recalled childhood gender role/identity is a construct that is related to sexual orientation, abuse, and psychological health. The purpose of this study was to assess the factorial validity of a short version of Zucker et al.'s (2006) "Recalled Childhood Gender Identity/Gender Role Questionnaire" using confirmatory factor analysis and to test the stability of the factor structure across groups (measurement invariance). Six items of the questionnaire were completed online by 1929 participants from a variety of gender identity and sexual orientation groups. Models of the six items loading onto one factor had poor fit for the data. Items were removed for having a large proportion of error variance. Among birth-assigned females, a five-item model had good fit for the data, but there was evidence for differences in scale's factor structure across gender identity, age, level of education, and country groups. Among birth-assigned males, the resulting four-item model did not account for all of the relationship between variables, and modeling for this resulted in a model that was almost saturated. This model also had evidence of measurement variance across gender identity and sexual orientation groups. The models had good reliability and factor score determinacy. These findings suggest that results of previous studies that have assessed recalled childhood gender role/identity may have been susceptible to construct bias due to measurement variance across these groups. Future studies should assess measurement invariance between groups they are comparing, and if it is not found the issue can be addressed by removing variant indicators and/or applying a partial invariance model. PMID- 26864872 TI - Interplay between aromaticity and strain in double group transfer reactions to 1,2-benzyne. AB - Density Functional Theory calculations are used to explore the double hydrogen atom transfer from different alkanes to 1,2-benzyne. State-of-the-art calculations including the Activation Strain Model of reactivity, Energy Decomposition Analysis, and Valence Bond methods, reveal the origins of the relatively low activation barriers computed for these processes compared to the analogous reaction involving acetylene. In addition, the interplay between the in plane aromaticity of the corresponding transition states and the variation of the pi-aromaticity associated with the benzyne moiety as well as their influence on the barrier heights of the transformations are analyzed in detail. PMID- 26864873 TI - Responses of fish assemblages of sandy beaches to different anthropogenic and hydrodynamic influences. AB - This study tested whether some attributes of the diversity, communities and populations of surf-zone fish assemblages varied with different hydrodynamic and anthropogenic influences at four Guanabara Bay sandy beaches: Dentro (sheltered with limited human access), Fora (exposed with limited human access), Urca (sheltered with unlimited human access) and Vermelha (exposed with unlimited human access), between autumn 2011 and summer 2012. Twenty-nine species and 1613 individuals were recorded from 76 trawls. The 10 most abundant species accounted for 94.5% of the total number, but only four species (Diplodus argenteus, Harengula clupeola, Sardinella brasiliensis and Sphoeroides greeleyi) were recorded at all four beaches, revealing a high level of species substitution. Fish assemblages differed not only for diversity attributes, but also at community and population levels, with lower values of the Shannon-Wiener index, richness and total fish abundance and biomass at Vermelha beach, and higher densities of Trachinotus carolinus, Atherinella brasiliensis and S. greeleyi related to beaches with high anthropogenic influence. The findings reveal that fish assemblages of Dentro, Fora, Urca and Vermelha beaches differed not only in response to hydrodynamic influences, but also due to the effects of different degrees of human interference (i.e. presence of solid residues, population density and fishing impacts), emphasizing the importance of the sheltered and less anthropogenically affected beaches, as spawning, nursery and growth areas. PMID- 26864874 TI - Confined-Volume Effect on the Thermal Properties of Encapsulated Phase Change Materials for Thermal Energy Storage. AB - We have encapsulated the heat exchange material, n-docosane, into polyurethane capsules of different sizes. Decreasing the size of the capsules leads to changes of the crystallinity of phase-change material as well as melting/crystallization temperature. The novelty of the paper includes 1) protection of the nanostructured energy-enriched materials against environment during storage and controlled release of the encapsulated energy on demand and 2) study of the structure and surface-to-volume properties of the energy-enriched materials dispersed in capsules of different sizes. The stability of energy nanomaterials, influence of capsule diameter on their energy capacity, homogeneity and operation lifetime are investigated. PMID- 26864875 TI - Survival in primary antiphospholipid syndrome. A single-centre cohort study. AB - The vascular mortality of antiphospholipid syndrome (APS) ranges from 1.4 % to 5.5 %, but its predictors are poorly known. It was the study objective to evaluate the impact of baseline lupus anticoagulant assays, IgG anticardiolipin (aCL), plasma fibrinogen (FNG) and von Willebrand factor (VWF), platelets (PLT) and of genetic polymorphisms of methylenetetrahydrofolate reductase C677T, of prothrombin G20210A and of paraoxonase-1 Q192R on survival in primary APS (PAPS). Cohort study on 77 thrombotic PAPS and 33 asymptomatic carriers of aPL (PCaPL) seen from 1989 to 2015 and persistently positive for aPL as per annual review. At baseline all participants were tested twice for the ratios of kaolin clotting time (KCTr), activated partial thromboplastin time (aPTTr), dilute Russell viper venom time (DRVVTr), IgG aCL, FNG, VWF and once for PLT. All thrombotic PAPS were on warfarin with regular INR monitoring. During follow-up 11 PAPS deceased (D PAPS) of recurrent thrombosis mostly arterial, despite adequate anticoagulation yielding an overall vascular mortality of 10 %. D-PAPS had the strongest baseline aPTTr and DRVVTr and the highest mean baseline IgG aCL, FNG, VWF and PLT. Cox proportional hazards model identified baseline DRVVTr and FNG as main predictors of mortality with adjusted hazard ratios of 5.75 (95 % confidence interval [CI]: 1.5, 22.4) and of 1.03 (95 %CI: 1.01, 1.04), respectively. In conclusion, plasma DRVVTr and FNG are strongly associated with the risk of vascular death in PAPS; while FNG lowering agents exist further research should be directed at therapeutic strategies able to dampen aPL production. PMID- 26864876 TI - Rewritable Optical Storage with a Spiropyran Doped Liquid Crystal Polymer Film. AB - Rewritable optical storage has been obtained in a spiropyran doped liquid crystal polymer films. Pictures can be recorded on films upon irradiation with UV light passing through a grayscale mask and they can be rapidly erased using visible light. Films present improved photosensitivity and optical contrast, good resistance to photofatigue, and high spatial resolution. These photochromic films work as a multifunctional, dynamic photosensitive material with a real-time image recording feature. PMID- 26864877 TI - Biological synthesis of Au nanoparticles using liquefied mash of cassava starch and their functionalization for enhanced hydrolysis of xylan by recombinant xylanase. AB - Au nanoparticles (AuNPs) have shown the potential for a variety of applications due to their unique physical and chemical properties. In this study, a facile and affordable method for the synthesis of AuNPs via the liquefied mash of cassava starch has been described and the functionalized AuNPs by L-cysteine improved activity of recombinant xylanase was demonstrated. UV-Vis absorption spectroscopy, transmission electron microscopy, and zeta potential measurements were performed to characterize the AuNPs and monitor their synthesis. The presence of Au was confirmed by energy-dispersive X-ray spectroscopy (EDX) and the X-ray diffraction patterns showed that Au nanocrystals were face-centered cubic. The C=O stretching vibration in the Fourier transform infrared spectrum of AuNPs suggested that the hemiacetal C-OH of sugar molecules performed the reduction of Au3+ to Au0. The presence of C and O in the EDX spectrum and the negative zeta potential of AuNPs suggested that the biomolecules present in liquefied cassava mash were responsible for the stabilization of AuNPs. The surface of AuNPs was easily functionalized by L-cysteine, which improved the stability of AuNPs. Moreover, cysteine-functionalized AuNPs could significantly improve recombinant xylanase efficiency and stability. PMID- 26864878 TI - Serotonin modulates Arabidopsis root growth via changes in reactive oxygen species and jasmonic acid-ethylene signaling. AB - Serotonin (5-hydroxytryptamine) is a bioactive indoleamine with neurotransmitter function in vertebrates, which represents an emerging signaling molecule in plants, playing key roles in the development and defense. In this study, the role of reactive oxygen species (ROS) and jasmonic acid (JA)-ethylene (Et) signaling in root developmental alterations induced by serotonin was investigated. An Arabidopsis thaliana mutant defective at the RADICAL-INDUCED CELL DEATH1 (RCD1) locus was resistant to paraquat-induced ROS accumulation in primary roots and showed decreased inhibition or root growth in response to serotonin. A suite of JA- and Et-related mutants including coronatine insensitive1, jasmonic acid resistant1 (jar1), etr1, ein2 and ein3 showed tolerance to serotonin in the inhibition of primary root growth and ROS redistribution within the root tip when compared with wild-type (WT) seedlings. Competence assays between serotonin and AgNO3 , a well-known blocker of Et action, showed that primary root growth in medium supplemented with serotonin was normalized by AgNO3 , whereas roots of eto3, an Et overproducer mutant, were oversensitive to serotonin. Comparison of ROS levels in WT, etr1, jar1 and rcd1 primary root tips using the ROS-specific probe 2',7'-dichlorofluorescein diacetate and confocal imaging showed that serotonin inhibition of primary root growth likely occurs independently of its conversion into melatonin. Our results provide compelling evidence that serotonin affects ROS distribution in roots, involving RCD1 and components of the JA-Et signaling pathways. PMID- 26864879 TI - Altered behavioral and neural responsiveness to counterfactual gains in the elderly. AB - Counterfactual information processing refers to the consideration of events that did not occur in comparison to those actually experienced, in order to determine optimal actions, and can be formulated as computational learning signals, referred to as fictive prediction errors. Decision making and the neural circuitry for counterfactual processing are altered in healthy elderly adults. This experiment investigated age differences in neural systems for decision making with knowledge of counterfactual outcomes. Two groups of healthy adult participants, young (N = 30; ages 19-30 years) and elderly (N = 19; ages 65-80 years), were scanned with fMRI during 240 trials of a strategic sequential investment task in which a particular strategy of differentially weighting counterfactual gains and losses during valuation is associated with more optimal performance. Elderly participants earned significantly less than young adults, differently weighted counterfactual consequences and exploited task knowledge, and exhibited altered activity in a fronto-striatal circuit while making choices, compared to young adults. The degree to which task knowledge was exploited was positively correlated with modulation of neural activity by expected value in the vmPFC for young adults, but not in the elderly. These findings demonstrate that elderly participants' poor task performance may be related to different counterfactual processing. PMID- 26864880 TI - Combining electrostatic powder with an insecticide: effect on stored-product beetles and on the commodity. AB - BACKROUND: The opportunity to reduce the amount of pirimiphos-methyl applied to grain by formulating it in an electrostatic powder was investigated. The insecticidal efficacy of pirimiphos-methyl in EC formulation or formulated using electrostatic powder (EP) as an inert carrier was investigated against Sitophilus oryzae (L.), Oryzaephilus surinamensis (L.), Rhyzopertha dominica (F.) and Tribolium confusum Jacquelin du Val. Furthermore, the adhesive properties of EP to rice, corn and wheat, together with the effect on bulk density and bread- and pasta-making properties, were investigated. RESULTS: The results showed that pirimiphos-methyl formulated with EP provided better efficacy against adults when compared with EC formulation for O. surinamensis and T. confusum, but there was no difference for R. dominica. Progeny production was consistently lower in grain treated with the EP formulation than in grain treated with the EC. Tests showed that EP adhered to the kernels for longer on hard wheat than on maize or rice. In most commodities, EP did not alter the bulk density. Finally, the addition of EP did not affect flour- and bread-making properties, nor the pasta-making properties. CONCLUSIONS: The results of the present study suggest that an EP could be used to reduce the amount of pirimiphos-methyl applied to grain for effective pest control, with no detrimental effects on grain quality. (c) 2016 Society of Chemical Industry. PMID- 26864881 TI - Parasail: SIMD C library for global, semi-global, and local pairwise sequence alignments. AB - BACKGROUND: Sequence alignment algorithms are a key component of many bioinformatics applications. Though various fast Smith-Waterman local sequence alignment implementations have been developed for x86 CPUs, most are embedded into larger database search tools. In addition, fast implementations of Needleman Wunsch global sequence alignment and its semi-global variants are not as widespread. This article presents the first software library for local, global, and semi-global pairwise intra-sequence alignments and improves the performance of previous intra-sequence implementations. RESULTS: A faster intra-sequence local pairwise alignment implementation is described and benchmarked, including new global and semi-global variants. Using a 375 residue query sequence a speed of 136 billion cell updates per second (GCUPS) was achieved on a dual Intel Xeon E5-2670 24-core processor system, the highest reported for an implementation based on Farrar's 'striped' approach. Rognes's SWIPE optimal database search application is still generally the fastest available at 1.2 to at best 2.4 times faster than Parasail for sequences shorter than 500 amino acids. However, Parasail was faster for longer sequences. For global alignments, Parasail's prefix scan implementation is generally the fastest, faster even than Farrar's 'striped' approach, however the opal library is faster for single-threaded applications. The software library is designed for 64 bit Linux, OS X, or Windows on processors with SSE2, SSE41, or AVX2. Source code is available from https://github.com/jeffdaily/parasail under the Battelle BSD-style license. CONCLUSIONS: Applications that require optimal alignment scores could benefit from the improved performance. For the first time, SIMD global, semi-global, and local alignments are available in a stand-alone C library. PMID- 26864882 TI - Endoscopic diagnosis of colorectal serrated lesions: Current status and future perspectives based on the results of a questionnaire survey. AB - Serrated lesions, especially sessile serrated adenoma/polyps (SSA/P) are considered one of the most important precursors of colorectal cancers. However, it is still difficult to endoscopically differentiate SSA/P from hyperplastic polyps. In the present review, we mainly focus on the current status and future perspectives of endoscopic diagnosis of colorectal serrated lesions based on the results of a questionnaire survey and report from the Endoscopic Forum Japan (EFJ) 2015 held in Tokyo in August 2015. The proposed diagnostic strategy recommended for colorectal serrated lesions is as follows. (i) For detection, use of an updated image-enhanced endoscopy system including autofluorescence imaging (AFI) and narrow-band imaging (NBI) may be promising. (ii) For differential diagnosis (hyperplastic polyp or SSA/P) of diminutive, small and large serrated lesions, NBI with magnification and magnifying chromoendoscopy using both indigocarmine and crystal violet should be applied, respectively. (iii) For differential diagnosis of SSA/P (with or without cytological dysplasia), magnifying chromoendoscopy, endocytoscopy and updated AFI system modalities might be promising. PMID- 26864883 TI - In Situ Potentiometry and Ellipsometry: A Promising Tool to Study Biofouling of Potentiometric Sensors. AB - In situ potentiometry and null ellipsometry was combined and used as a tool to follow the kinetics of biofouling of ion-selective electrodes (ISEs). The study was performed using custom-made solid-contact K(+)-ISEs consisting of a gold surface with immobilized 6-(ferrocenyl)hexanethiol as ion-to-electron transducer that was coated with a potassium-selective plasticized polymer membrane. The electrode potential and the ellipsometric signal (corresponding to the amount of adsorbed protein) were recorded simultaneously during adsorption of bovine serum albumin (BSA) at the surface of the K(+)-ISEs. This in situ method may become useful in developing sensors with minimized biofouling. PMID- 26864884 TI - New modalities to deliver surfactant in premature infants: a systematic review and meta-analysis. AB - CONTEXT: Surfactant is the principle treatment of respiratory distress syndrome, but the ideal method of its administration remains controversial. The intubation, surfactant administration and extubation (InSurE) method is proven to work but is invasive. The objective of this systematic review is to evaluate the efficacy and safety of the modalities of surfactant administration. METHODS: We searched MEDLINE, EMBASE and CENTRAL (inception to December 2015) for randomized trials comparing new modalities with InSurE method. The primary outcome was mortality and development of bronchopulmonary dysplasia (BPD). RESULTS: We screened 1837 citations and identified five unique trials were included; all were of unclear risk of bias. Four trials (400 infants) compared endotracheal catheters with InSurE, and one trial (70 infants) compared laryngeal masks (LMA) with InSurE. There was no significant difference between using endotracheal catheters compared with InSurE regarding infant mortality (risk ratio 1.05, 95% CI 0.57-1.94, 4 trials, 400 patients, p 0.87, I(2) 0%) or BPD (risk ratio 0.73, 95% CI 0.43-1.21, 4 trials, 400 patients, p 0.22, I(2) 0%). Adverse events were under-reported. CONCLUSION: The use of endotracheal catheters may provide comparable results to the InSurE method. There is limited evidence on the comparative efficacy of LMA. PMID- 26864885 TI - Acute Presentation of Tender Papules and Plaques in a Patient With Leukemia. PMID- 26864886 TI - Longitudinal study of premorbid adjustment in 22q11.2 deletion (velocardiofacial) syndrome and association with psychosis. AB - Velocardiofacial syndrome, also known as 22q11.2 deletion syndrome (22q11DS), is associated with an increased risk of major psychiatric disorders, including schizophrenia. The emergence of psychotic symptoms in individuals with schizophrenia in the general population is often preceded by a premorbid period of poor or worsening social and/or academic functioning. Our current study evaluated premorbid adjustment (via the Cannon-Spoor Premorbid Adjustment Scale [PAS]) and psychotic symptoms (via the Structured Interview for Prodromal Symptoms and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) in youth with 22q11DS (N = 96), unaffected siblings (N = 40), and community controls (N = 50). The PAS scores indicated greater maladjustment during all developmental periods in individuals with 22q11DS compared to the controls. Many participants with 22q11DS had chronically poor (n = 33) or deteriorating (n = 6) PAS scores. In 22q11DS, chronically poor PAS trajectories and poor childhood and early adolescence academic domain and total PAS scores significantly increased the risk of prodromal symptoms or overt psychosis. Taking into account the catechol-O methyltransferase (COMT) genotype, the best predictor of (prodromal) psychosis was the early adolescence academic domain score, which yielded higher sensitivity and specificity in the subgroup of youth with 22q11DS and the high-activity (valine) allele. PAS scores may help identify individuals at higher risk for psychosis. PMID- 26864887 TI - Microfluidics-mediated assembly of functional nanoparticles for cancer-related pharmaceutical applications. AB - The controlled synthesis of functional nanoparticles with tunable structures and properties has been extensively investigated for cancer treatment and diagnosis. Among a variety of methods for fabrication of nanoparticles, microfluidics-based synthesis enables enhanced mixing and precise fluidic modulation inside microchannels, thus allowing for the flow-mediated production of nanoparticles in a controllable manner. This review focuses on recent advances of using microfluidic devices for the synthesis of drug-loaded nanoparticles with specific characteristics (such as size, composite, surface modification, structure and rigidity) for enhanced cancer treatment and diagnosis as well as to investigate the bio-nanoparticle interaction. The discussion on microfluidics-based synthesis may shed light on the rational design of functional nanoparticles for cancer related pharmaceutical applications. PMID- 26864888 TI - Psychologically informed practice (PIP) for staff working with offenders with personality disorder: A pragmatic exploratory trial in approved premises. AB - BACKGROUND: Rates of reoffending and recall are high among released male prisoners with personality disorder. There is a need for innovative intervention to reduce offending and increase staff confidence in working with such men. AIM: The aim of this study was to evaluate the effectiveness of a novel intervention consisting of training and consultation termed 'psychologically informed practice', within community-based 'approved premises' for offenders. METHOD: A pragmatic exploratory trial was used to compare two premises in a South London borough licenced under criminal justice legislation to provide supervised accommodation for selected released prisoners. One used the PIP intervention for 12 months while the other (comparison group) functioned in a similar way but without this intervention. Outcome measures included staff attitudes and offender behaviours. RESULTS: Significant improvements were observed only for the intervention group. Compared with baseline measures, significantly higher levels of knowledge and understanding of personality disorder as well as a greater sense of personal accomplishment were observed in staff who have been trained and supported in psychologically informed practice. Significantly lower rates of warnings and recalls to prison were observed only for the intervention group at 6 months following initial staff training. CONCLUSION: Psychologically informed practice appears to be sufficiently advantageous for staff and offenders, and the trial feasible, which is a full-scale multi-centre trial, seems warranted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864889 TI - Age-Associated Pathology in Rhesus Macaques (Macaca mulatta). AB - The rhesus macaque (Macaca mulatta) is one of the most extensively used nonhuman primate models for human diseases. This article presents a literature review focusing on major organ systems and age-associated conditions in humans and primates, combined with information from the Wisconsin National Primate Research Center Electronic Health Record database to highlight and contrast age-associated lesions in geriatric rhesus macaques with younger cohorts. Rhesus macaques are excellent models for age-associated conditions, including diabetes, osteoarthritis, endometriosis, visual accommodation, hypertension, osteoporosis, and amyloidosis. Adenocarcinoma of the large intestine (ileocecocolic junction, cecum, and colon) is the most common spontaneous neoplasm in the rhesus macaque. A combination of cross-sectional and longitudinal studies is required to truly define mechanisms of maturation, aging, and the pathology of age-associated conditions in macaques and thus humans. The rhesus macaque is and will continue to be an appropriate and valuable model for investigation of the mechanisms and treatment of age-associated diseases. PMID- 26864891 TI - Pathology of Mouse Models of Accelerated Aging. AB - Progeroid mouse models display phenotypes in multiple organ systems that suggest premature aging and resemble features of natural aging of both mice and humans. The prospect of a significant increase in the global elderly population within the next decades has led to the emergence of "geroscience," which aims at elucidating the molecular mechanisms involved in aging. Progeroid mouse models are frequently used in geroscience as they provide insight into the molecular mechanisms that are involved in the highly complex process of natural aging. This review provides an overview of the most commonly reported nonneoplastic macroscopic and microscopic pathologic findings in progeroid mouse models (eg, osteoporosis, osteoarthritis, degenerative joint disease, intervertebral disc degeneration, kyphosis, sarcopenia, cutaneous atrophy, wound healing, hair loss, alopecia, lymphoid atrophy, cataract, corneal endothelial dystrophy, retinal degenerative diseases, and vascular remodeling). Furthermore, several shortcomings in pathologic analysis and descriptions of these models are discussed. Progeroid mouse models are valuable models for aging, but thorough knowledge of both the mouse strain background and the progeria-related phenotype is required to guide interpretation and translation of the pathology data. PMID- 26864892 TI - Species-dependent hydrodynamics of flagellum-tethered bacteria in early biofilm development. AB - Monotrichous bacteria on surfaces exhibit complex spinning movements. Such spinning motility is often a part of the surface detachment launch sequence of these cells. To understand the impact of spinning motility on bacterial surface interactions, we develop a hydrodynamic model of a surface-bound bacterium, which reproduces behaviours that we observe in Pseudomonas aeruginosa, Shewanella oneidensis and Vibrio cholerae, and provides a detailed dictionary for connecting observed spinning behaviour to bacteria-surface interactions. Our findings indicate that the fraction of the flagellar filament adhered to the surface, the rotation torque of this appendage, the flexibility of the flagellar hook and the shape of the bacterial cell dictate the likelihood that a microbe will detach and the optimum orientation that it should have during detachment. These findings are important for understanding species-specific reversible attachment, the key transition event between the planktonic and biofilm lifestyle for motile, rod shaped organisms. PMID- 26864894 TI - Correction to 'Single passage in mouse organs enhances the survival and spread of Salmonella enterica'. PMID- 26864893 TI - From the primordial soup to self-driving cars: standards and their role in natural and technological innovation. AB - Standards are specifications to which the elements of a technology must conform. Here, we apply this notion to the biochemical 'technologies' of nature, where objects like DNA and proteins, as well as processes like the regulation of gene activity are highly standardized. We introduce the concept of standards with multiple examples, ranging from the ancient genetic material RNA, to Palaeolithic stone axes, and digital electronics, and we discuss common ways in which standards emerge in nature and technology. We then focus on the question of how standards can facilitate technological and biological innovation. Innovation enhancing standards include those of proteins and digital electronics. They share common features, such as that few standardized building blocks can be combined through standard interfaces to create myriad useful objects or processes. We argue that such features will also characterize the most innovation-enhancing standards of future technologies. PMID- 26864895 TI - Families dealing with the uncertainty of genetic disorders: the case of Neurofibromatosis Type 1. AB - Some scholars contend that genetic medicine is transforming the experience of illness and the social category of the family - bringing future risks into the present, and potentially strengthening familial biological bonds in light of these shared genetic risks. However, research has shown that genetic information is interpreted and acted upon through a rich repertoire of adaptable social, cultural and familial factors which pre-exist and interact with biomedical knowledge. This paper reports research into families living with Neurofibromatosis Type 1 (NF1), a highly uncertain condition the manifestation of which can vary considerably also within the same family and, for this reason, has been defined as a 'condition without parameters'. These characteristics make NF1 a particularly informative condition for the examination of family dynamics around genetic information. The study and the methodology are based on the exploration of family networks and allow us to investigate the interrelation of individual and familial constructions of the uncertainty of NF1. This also allows both theoretical and policy claims to be made about the danger of reductionist thinking about the transformative potential of genetic technologies. PMID- 26864897 TI - Implementation of Web-based Education for Patients with Chronic Skin Disease. PMID- 26864896 TI - Multiplex PCR assay for simultaneous detection of six major bacterial pathogens of rice. AB - AIMS: The aim of this study was to develop a multiplex PCR (mPCR) assay for rapid, sensitive and simultaneous detection of six important rice pathogens: Xanthomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, Pseudomonas fuscovaginae, Burkholderia glumae, Burkholderia gladioli and Acidovorax avenae subsp. avenae. METHODS AND RESULTS: Specific primers were designed through a bioinformatics pipeline. Sensitivity of detection was established using both traditional PCR and quantitative real-time PCR on isolated DNA and on bacterial cells both in vitro and in simulated diseased seeds and the parameters were optimized for an mPCR assay. A total of 150 bacterial strains were tested for specificity. The mPCR assay accurately predicted the presence of pathogens among 44 symptomatic and asymptomatic rice seed, sheath and leaf samples. CONCLUSIONS: This study confirmed that this mPCR assay is a rapid, reliable and simple tool for the simultaneous detection of six important rice bacterial pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first report of a method allowing simultaneous detection of six major rice pathogens. The ability to use crude extracts from plants without bacterial isolation or DNA extraction enhances the value of this mPCR technology for rapid detection and aetiological/epidemiological studies. PMID- 26864898 TI - Revascularisation plus supervised exercise is superior to supervised exercise alone for the treatment of intermittent claudication. PMID- 26864899 TI - The combination of maternal early pregnancy characteristics and current antenatal blood pressure measurement from 28 weeks' gestation improves the prediction of women at risk of developing pre-eclampsia. PMID- 26864900 TI - Drug-eluting stents and drug-eluting balloons are the best strategies to treat coronary in-stent restenosis. PMID- 26864903 TI - Cytotoxic activity and chemical constituents of Anthemis mirheydari. AB - Context The genus Anthemis L. (Asteraceae) comprises about 195 species which are widely used in the pharmaceutical, cosmetic and food industries. Objective Anthemis mirheydari Iranshar, an endemic plant from Iran, was investigated for its cytotoxic properties and chemical constituents. Materials and methods The whole parts of the plant (320 g) were extracted by dichloromethane and methanol for four days, successively. The cytotoxic activity of both dichloromethane and methanol extracts were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide colorimetric methods against three human cancer cell lines including LS180, MCF-7 and MOLT-4. Different concentrations (10-100 MUg/mL) of the plant extracts were tested to obtain IC50 values. The dichloromethane extract of A. mirheydari was subjected to silica gel-column and thin layer chromatography for purification of its chemical constituents and the isolated compounds were further tested against MOLT-4 cells. The structures of the pure compounds were elucidated using different spectral data including nuclear magnetic resonance and electron impact mass spectra. Results The IC50 values of the dichloromethane extract were 30.8 +/- 6.7, 25.2 +/- 6.5 and 8.6 +/- 1.1 MUg/mL (means +/- standard error) for the above-mentioned cell lines, respectively. Two triterpenoids, taraxasterol (1) and pseudotaraxasterol (2), one sterol, beta-sitosterol (3) and one coumarin, 7-methoxycoumarin (4) were isolated from the extract. The IC50 of the mixture of compounds 1 and 2 as well as compounds 3 and 4 were higher (>100 MUM) than that reported for the dichloromethane extract against MOLT-4 cells. Conclusion The dichloromethane extract was the most active one among the tested material. PMID- 26864905 TI - C15083. Chemical Composition and Allelopathic Potential of Essential Oils from Tipuana tipu (Benth.) Kuntze Cultivated in Tunisia. AB - In Tunisia, Tipuana tipu (Benth.) Kuntze is an exotic tree, which was introduced many years ago and planted as ornamental street, garden, and park tree. The present work reported, for the first time, the chemical composition and evaluates the allelopathic effect of the hydrodistilled essential oils of the different parts of this tree, viz., roots, stems, leaves, flowers and pods gathered in the area of Sousse, a coastal region, in the East of Tunisia. In total, 86 compounds representing 89.9-94.9% of the whole oil composition, were identified in these oils by GC-FID and GC/MS analyses. The root essential oil was clearly distinguished for its high content in sesquiterpene hydrocarbons (beta caryophyllene, 1 (44); 24.1% and germacrene D, 2 (53); 20.0%), while those obtained from pods, leaves, stems and flowers were dominated by non-terpene hydrocarbons. The most important ones were n-tetradecane (41, 16.3%, pod oil), 1.7-dimethylnaphthalene (43, 15.6%, leaf oil), and n-octadecane (77, 13.1%, stem oil). The leaf oil was rich in the apocarotene (E)-beta-ionone (4 (54); 33.8%), and the oil obtained from flowers was characterized by hexahydrofarnesyl acetone (5 (81); 19.9%) and methyl hexadecanoate (83, 10.2%). Principal component and hierarchical cluster analyses separated the five essential oils into 3 groups and 2 subgroups, each characterized by the major oil constituents. Contact tests showed that the germination of lettuce seeds was totally inhibited by the root essential oil tested at 1 mg/ml. The inhibitory effect on the shoot and root elongation varied from -1.6 to -32.4%, and from -2.5 to -64.4%, respectively. This article is protected by copyright. All rights reserved. PMID- 26864904 TI - Real-time kinetics of electrogenic Na(+) transport by rhodopsin from the marine flavobacterium Dokdonia sp. PRO95. AB - Discovery of the light-driven sodium-motive pump Na(+)-rhodopsin (NaR) has initiated studies of the molecular mechanism of this novel membrane-linked energy transducer. In this paper, we investigated the photocycle of NaR from the marine flavobacterium Dokdonia sp. PRO95 and identified electrogenic and Na(+)-dependent steps of this cycle. We found that the NaR photocycle is composed of at least four steps: NaR519 + hv -> K585 -> (L450<->M495) -> O585 -> NaR519. The third step is the only step that depends on the Na(+) concentration inside right-side out NaR-containing proteoliposomes, indicating that this step is coupled with Na(+) binding to NaR. For steps 2, 3, and 4, the values of the rate constants are 4*10(4) s(-1), 4.7 * 10(3) M(-1) s(-1), and 150 s(-1), respectively. These steps contributed 15, 15, and 70% of the total membrane electric potential (Deltapsi ~ 200 mV) generated by a single turnover of NaR incorporated into liposomes and attached to phospholipid-impregnated collodion film. On the basis of these observations, a mechanism of light-driven Na(+) pumping by NaR is suggested. PMID- 26864906 TI - Identification of a new HLA-B allele, HLA-B*15:300, in a Chinese individual. AB - HLA-B*15:300 differs from B*15:01:01:01 by one nucleotide exchange at position 540(G > C) with an amino exchange. PMID- 26864902 TI - hCLE/C14orf166, a cellular protein required for viral replication, is incorporated into influenza virus particles. AB - The influenza A virus polymerase associates with a number of cellular transcription-related factors, including the RNA polymerase II (RNAP II). We previously described that the cellular protein hCLE/C14orf166 interacts with and stimulates influenza virus polymerase as well as RNAP II activities. Here we show that, despite the considerable cellular shut-off observed in infected cells, which includes RNAP II degradation, hCLE protein levels increase throughout infection in a virus replication-dependent manner. Human and avian influenza viruses of various subtypes increase hCLE levels, but other RNA or DNA viruses do not. hCLE colocalises and interacts with viral ribonucleoproteins (vRNP) in the nucleus, as well as in the cytoplasm late in infection. Furthermore, biochemical analysis of purified virus particles and immunoelectron microscopy of infected cells show hCLE in virions, in close association with viral vRNP. These findings indicate that hCLE, a cellular protein important for viral replication, is one of the very few examples of transcription factors that are incorporated into particles of an RNA-containing virus. PMID- 26864907 TI - Spatial location of indomethacin associated with unimeric amphiphilic carrier macromolecules as determined by nuclear magnetic resonance spectroscopy. AB - A combination of nuclear magnetic resonance (NMR) techniques including, proton NMR, relaxation analysis, two-dimensional nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy, has been used to demonstrate the spatial location of indomethacin within a unimolecular micelle. Understanding the location of drugs within carrier molecules using such NMR techniques can facilitate rational carrier design. In addition, this information provides insight to encapsulation efficiency of different drugs to determine the most efficient system for a particular bioactive. This study demonstrates that drugs loaded by the unimolecular amphiphile under investigation are not necessarily encapsulated but reside or localize to the periphery or interfacial region of the carrier molecule. The results have further implications as to the features of the unimolecular carrier that contribute to drug loading. In addition, evidence of drug retention associated with the unimolecular surfactant is possible in organic media, as well as in an aqueous environment. Such findings have implications for rational carrier design to correlate the carrier features to the drug of interest and indicate the strong retention capabilities of the unimolecular micelle for delivery applications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26864908 TI - Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. AB - While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long-term senolytic treatment is unknown. To determine whether long-term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease. Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senescent cell markers (TAF(+) cells) in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function (isolated organ chamber baths) in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Genetic clearance of senescent cells in aged normocholesterolemic INK-ATTAC mice phenocopied changes elicited by D+Q. Senolytics tended to reduce aortic calcification (alizarin red) and osteogenic signaling (qRT-PCR, immunohistochemistry) in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis (picrosirius red) was not changed appreciably by chronic senolytic treatment. This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases. PMID- 26864909 TI - Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery. AB - BACKGROUND: Postoperative hypoparathyroidism remains the most common complication following thyroidectomy. The aim of this pilot study was to evaluate the use of intraoperative parathyroid gland angiography in predicting normal parathyroid gland function after thyroid surgery. METHODS: Angiography with the fluorescent dye indocyanine green (ICG) was performed in patients undergoing total thyroidectomy, to visualize vascularization of identified parathyroid glands. RESULTS: Some 36 patients underwent ICG angiography during thyroidectomy. All patients received standard calcium and vitamin D supplementation. At least one well vascularized parathyroid gland was demonstrated by ICG angiography in 30 patients. All 30 patients had parathyroid hormone (PTH) levels in the normal range on postoperative day (POD) 1 and 10, and only one patient exhibited asymptomatic hypocalcaemia on POD 1. Mean(s.d.) PTH and calcium levels in these patients were 3.3(1.4) pmol/l and 2.27(0.10) mmol/l respectively on POD 1, and 4.0(1.6) pmol/l and 2.32(0.08) mmol/l on POD 10. Two of the six patients in whom no well vascularized parathyroid gland could be demonstrated developed transient hypoparathyroidism. None of the 36 patients presented symptomatic hypocalcaemia, and none received treatment for hypoparathyroidism. CONCLUSION: PTH levels on POD 1 were normal in all patients who had at least one well vascularized parathyroid gland demonstrated during surgery by ICG angiography, and none required treatment for hypoparathyroidism. PMID- 26864910 TI - Structure-Triggered High Quantum Yield Luminescence and Switchable Dielectric Properties in Manganese(II) Based Hybrid Compounds. AB - Two new manganese(II) based organic-inorganic hybrid compounds, C11H21Cl3MnN2 (1) and C11H22Cl4MnN2 (2), with prominent photoluminescence and dielectric properties were synthesized by solvent modulation. Compound 1 with novel trigonal bipyramidal geometry exhibits bright red luminescence with a lifetime of 2.47 ms and high quantum yield of 35.8 %. Compound 2 with tetrahedral geometry displays intense long-lived (1.54 ms) green light emission with higher quantum yield of 92.3 %, accompanied by reversible solid-state phase transition at 170 K and a distinct switchable dielectric property. The better performance of 2 results from the structure, including a discrete organic cation moiety and inorganic metal anion framework, which gives the cations large freedom of motion. PMID- 26864911 TI - Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) contamination from textiles. AB - The goals of this study were to determine the concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in textiles and to determine PFOS and PFOA contamination in textile washing water. Quantification analysis was performed by high performance liquid chromatography coupled with tandem mass spectrometry. Analysis of 32 textile samples by methanol extraction revealed that the average concentrations of PFOS and PFOA were 0.18 ug m(-2) (0.02 to 0.61 ug m(-2)) and 2.74 ug m(-2) (0.31 to 14.14 ug m(-2)), respectively. Although the average concentration of PFOS found in textile samples was below European Union (EU) Commission regulations (<1 ug m(-2)), the average concentration of PFOA was 2.74 ug m(-2), and 68.75% of textile samples had PFOA concentrations exceeding 1 ug m(-2). Thus, based on these results, the concentration of PFOA in products should also be regulated. Experiments on PFOS and PFOA leaching into washing water were conducted. The maximum concentrations of PFOS and PFOA were measured after the first washing; the concentrations gradually decreased with each subsequent washing. PFOS and PFOA migrated from textiles and were released into the environment, with disappearance percentages of 29.8% for PFOS and 99% for PFOA. The data presented in this study showed that textiles could be a significant direct and indirect source of PFOS and PFOA exposure for both humans and the environment. PMID- 26864913 TI - Coronary artery disease: Can aminothiols be distinguished from reactive oxygen species? PMID- 26864912 TI - Assessment, treatment, and prognostic implications of CAD in patients undergoing TAVI. AB - Coronary artery disease (CAD) is common in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), but its clinical relevance is controversial. At present, the optimal means of defining CAD in patients undergoing TAVI with respect to its prognostic implications and the assessment of myocardial ischaemia is not known. For this reason, the best treatment options are a matter for debate, and current guidelines do not recommend revascularization. As the indications for TAVI expand, the lack of any rigorous means of guiding coronary revascularization might negatively affect the clinical outcomes of future patients. In this Review, we summarize the methods of assessing CAD in TAVI populations, and the data on the safety and efficacy of percutaneous coronary intervention in patients undergoing TAVI. We discuss the putative effects of aortic stenosis on the functional assessment of CAD using pressure or flow wires or by noninvasive stress testing. We propose that a new, well-validated method of assessing CAD as a cause of myocardial ischaemia--which distinguishes it from myocardial infarction, previous revascularization, or non flow-limiting disease--in patients with severe aortic stenosis is needed to guide revascularization in the current era of TAVI. PMID- 26864914 TI - Heart failure: Ketone bodies as fuel in heart failure. PMID- 26864915 TI - Risk factors: Negative risk markers for CVD. PMID- 26864916 TI - Progranulin suppresses titanium particle induced inflammatory osteolysis by targeting TNFalpha signaling. AB - Aseptic loosening is a major complication of prosthetic joint surgery, characterized by chronic inflammation, pain, and osteolysis surrounding the bone implant interface. Progranulin (PGRN) is known to have anti-inflammatory action by binding to Tumor Necrosis Factor (TNF) receptors and antagonizing TNFalpha. Here we report that titanium particles significantly induced PGRN expression in RAW264.7 cells and also in a mouse air-pouch model of inflammation. PGRN deficiency enhanced, whereas administration of recombinant PGRN effectively inhibited, titanium particle-induced inflammation in an air pouch model. In addition, PGRN also significantly inhibited titanium particle-induced osteoclastogenesis and calvarial osteolysis in vitro, ex vivo and in vivo. Mechanistic studies demonstrated that the inhibition of PGRN on titanium particle induced-inflammation is primarily via neutralizing the titanium particle activated TNFalpha/NF-kappaB signaling pathway and this is evidenced by the suppression of particle-induced IkappaB phosphorylation, NF-kappaB p65 nuclear translocation, and activity of the NF-kappaB-specific reporter gene. Collectively, these findings not only demonstrate that PGRN plays an important role in inhibiting titanium particle-induced inflammation, but also provide a potential therapeutic agent for the prevention of wear debris-induced inflammation and osteolysis. PMID- 26864918 TI - Evolution of postirradiated sudden deafness in nasopharyngeal carcinoma survivors during the past two decades. AB - OBJECTIVE/HYPOTHESIS: The beneficial effect of intensity-modulated radiotherapy (IMRT) on reducing the prevalence of postirradiated sudden deafness (PISD) in nasopharyngeal carcinoma (NPC) survivors has never been mentioned. This study investigated the evolution of PISD in NPC survivors during the past two decades. STUDY DESIGN: Retrospective study. METHODS: Of the 3,206 NPC patients who underwent radiotherapy during the past two decades, 32 patients (34 ears) had PISD. Twenty-nine patients (30 ears) received two-dimensional radiotherapy (2DRT) and were assigned to group A, whereas three patients (4 ears) undergoing IMRT were assigned to group B. An inner ear test battery including audiometry, vestibular-evoked myogenic potential (VEMP) test, and caloric test was performed for comparison between the two groups. RESULTS: Group B (0.2%) showed significantly lower prevalence of PISD than group A (2%). Percentages of abnormal pursuit, saccade, and optokinetic nystagmus test results revealed nonsignificant difference between groups A and B. Likewise, both groups did not differ significantly in the percentages of abnormal pure tone average, cervical VEMP test, and caloric test. However, significant hearing improvement after treatment was identified in group B (P < 0.01) but not in group A (P > 0.05), probably because mean radiation dosage to the cochela of group B (35.0 +/- 0.4 gray units [Gy]) was less than group A (50 +/- 3 Gy). CONCLUSION: Compared to 2DRT, both radiation dosages to the cochlea and radiation damage to tissues surrounding the inner ear are lessened by IMRT. Therefore, NPC survivors who received IMRT have a low prevalence of PISD, with significant hearing improvement after treatment. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2016-2021, 2016. PMID- 26864917 TI - Discovery of Novel Allosteric Eg5 Inhibitors Through Structure-Based Virtual Screening. AB - Mitotic kinesin Eg5 is an attractive anticancer drug target. Discovery of Eg5 inhibitors has been focused on targeting the 'monastrol-binding site'. However, acquired drug resistance has been reported for such inhibitors. Therefore, identifying new Eg5 inhibitors which function through a different mechanism(s) could complement current drug candidates and improve drug efficacy. In this study, we explored a novel allosteric site of Eg5 and identified new Eg5 inhibitors through structure-based virtual screening. Experiments with the saturation-transfer difference NMR demonstrated that the identified Eg5 inhibitor SRI35566 binds directly to Eg5 without involving microtubules. Moreover, SRI35566 and its two analogs significantly induced monopolar spindle formation in colorectal cancer HCT116 cells and suppressed cancer cell viability and colony formation. Together, our findings reveal a new allosteric regulation mechanism of Eg5 and a novel drug targeting site for cancer therapy. PMID- 26864919 TI - Effects of Manipulation on Attributions of Causation, Free Will, and Moral Responsibility. AB - If someone brings about an outcome without intending to, is she causally and morally responsible for it? What if she acts intentionally, but as the result of manipulation by another agent? Previous research has shown that an agent's mental states can affect attributions of causal and moral responsibility to that agent, but little is known about what effect one agent's mental states can have on attributions to another agent. In Experiment 1, we replicate findings that manipulation lowers attributions of responsibility to manipulated agents. Experiments 2-7 isolate which features of manipulation drive this effect, a crucial issue for both philosophical debates about free will and attributions of responsibility in situations involving social influence more generally. Our results suggest that "bypassing" a manipulated agent's mental states generates the greatest reduction in responsibility, and we explain our results in terms of the effects that one agent's mental states can have on the counterfactual relations between another agent and an outcome. PMID- 26864920 TI - Different mechanisms of risperidone result in improved interpersonal trust, social engagement and cooperative behavior in patients with schizophrenia compared to trifluoperazine. AB - AIM: Atypical antipsychotic treatment (e.g. risperidone) has been found to improve social functioning more than standard antipsychotic treatment. However, it is unclear which specific social behaviors are implicated in this improvement. The current study employed an interactive puzzle game to examine how social behaviors contribute to the improvement of social functioning by comparing patients receiving risperidone with those receiving trifluoperazine. METHODS: Scores on the Positive and Negative Syndrome Scale, executive functioning, and social functioning were obtained from 24 patients with schizophrenia receiving either risperidone (n = 12) or trifluoperazine (n = 12), before their social behavior was measured in the interactive Tangrams Game. Immediately after the Tangrams Game, participants filled in two questionnaires measuring their interpersonal trust and rejection toward their game partner. RESULTS: Patients receiving risperidone showed more social engagement, cooperative behavior and interpersonal trust toward their game partners than those receiving trifluoperazine. Additional multivariate analysis of variance revealed that lower affiliative behavior was a function of positive symptoms; interpersonal trust had an impact on social engagement but executive functioning did not explain lower interpersonal trust or social disengagement. CONCLUSION: Improvement of social competence by risperidone might be related to the enhancement of both social behaviors and interpersonal trust as well as better symptom resolution. PMID- 26864922 TI - New Resources--Reviews and Podcasts. PMID- 26864921 TI - Looks and linguistics: Impression formation in online exchange marketplaces. AB - This study advances theories of impression formation by focusing on two factors that generate emotional responses: physical attractiveness and positive word use. Although considerable research on impression formation exists, most studies consider factors in isolation and neglect possible interactions. Our theory introduces competing mechanisms regarding possible interaction effects, and we empirically test them in an online marketplace. Results from the analysis of 729 loan requests from a leading online peer-to-peer lending market suggest that physical attractiveness and positive word use work together to influence the likelihood of acquiring resources and establish an important boundary condition to the general "beauty is good" effect. PMID- 26864923 TI - Growing Into the Nutrition Education Profession. PMID- 26864925 TI - Advancing the Field: Language and Training for Inclusion of LGBT Communities in Nutrition Programming. PMID- 26864926 TI - E-Cigarettes May Lead to Youth Tobacco Use: Evidence Mounts. PMID- 26864924 TI - Validation of Interviewer-Assisted Recall for Measuring Minutes of Moderate to Vigorous Physical Activity in Elementary School Children, Grades 3 and 5. AB - OBJECTIVE: To test the validity of interviewer-administered recall for measuring moderate to vigorous physical activity (MVPA) in third- and fifth-grade children who reported physical activity (PA) only or both PA and diet, using a short (same day recall in the afternoon) or long (previous-day recall in the morning) retention interval. METHODS: Randomly selected children (n = 95) wore an accelerometer 1 day in school. Interviews occurred in the afternoon of the day on which the accelerometer was worn or on the next morning. Assignment to interview content was random. Spearman correlations were calculated between MVPA interview and MVPA accelerometer minutes. RESULTS: The MVPA interview minutes were positively associated with the MVPA accelerometer minutes when the interview focused on PA only (r = .34; P = .02) but not when children recalled PA and diet (r = .12; P = .40). The MVPA interview minutes for the previous day was associated with the MVPA accelerometer minutes (r = .33; P = .02), but not for the same day (r = .17; P = .26). CONCLUSIONS: A recall interview method that focuses solely on PA is a promising approach to assessing children's school-day PA. PMID- 26864927 TI - Deep Sequencing of Acute Myeloid Leukemia Reveals Driver Mutations and New Targets. PMID- 26864929 TI - Bovine Leukemia Virus Possibly Linked to Breast Cancer. PMID- 26864931 TI - American Cancer Society Changes Breast Cancer Screening Guidelines To Reflect Analysis of Benefits and Harms. PMID- 26864932 TI - Patient preferences and access to text messaging for health care reminders in a safety-net setting. AB - INTRODUCTION: Text messaging may be an effective method for providing health care reminders to patients. We aimed to understand patient access to and preferences for receiving health-related reminders via text message among patients receiving care in safety-net hospitals. MATERIALS AND METHODS: We conducted face-to-face surveys with 793 patients seeking care in three hospital emergency departments at a large safety-net institution and determined clinical and demographic predictors of preferences for text messaging for health care reminders. RESULTS: 95% of respondents reported having daily access to text messaging. Text messaging was preferred over e-mail, phone, and letters for communication. 78% of respondents wanted to receive appointment reminders, 56% wanted expiring insurance reminders, and 36% wanted reminders to take their medications. We found no clinical predictors but did find some demographic predictors-including age, ethnicity, insurance status, and income-of wanting text message reminders. DISCUSSION: In our convenience sample of safety-net patients, text messaging is an accessible, acceptable, and patient-preferred modality for receiving health care reminders. Text messaging may be a promising patient-centered approach for providing health care and insurance reminders to patients seeking care at safety-net institutions. PMID- 26864933 TI - Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study. AB - AIM: Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure. MATERIALS & METHODS: Here, we examined the potential of DNA methylation changes in 910 prediagnostic peripheral blood samples as a marker of exposure to tobacco smoke in a large multinational cohort. RESULTS: We identified 748 CpG sites that were differentially methylated between smokers and nonsmokers, among which we identified novel regionally clustered CpGs associated with active smoking. Importantly, we found a marked reversibility of methylation changes after smoking cessation, although specific genes remained differentially methylated up to 22 years after cessation. CONCLUSION: Our study has comprehensively cataloged the smoking-associated DNA methylation alterations and showed that these alterations are reversible after smoking cessation. PMID- 26864934 TI - ANGPTL8/Betatrophin R59W variant is associated with higher glucose level in non diabetic Arabs living in Kuwaits. AB - BACKGROUND: ANGPTL8 (betatrophin) has been recently identified as a regulator of lipid metabolism through its interaction with ANGPTL3. A sequence variant in ANGPTL8 has been shown to associate with lower level of Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL). The objective of this study is to identify sequence variants in ANGPTL8 gene in Arabs and investigate their association with ANGPTL8 plasma level and clinical parameters. METHODS: A cross sectional study was designed to examine the level of ANGPTL8 in 283 non-diabetic Arabs, and to identify its sequence variants using Sanger sequencing and their association with various clinical parameters. RESULTS: Using Sanger sequencing, we sequenced the full ANGPTL8 gene in 283 Arabs identifying two single nucleotide polymorphisms (SNPs) Rs.892066 and Rs.2278426 in the coding region. Our data shows for the first time that Arabs with the heterozygote form of (c.194C > T Rs.2278426) had higher level of Fasting Blood Glucose (FBG) compared to the CC homozygotes. LDL and HDL level in these subjects did not show significant difference between the two subgroups. Circulation level of ANGPTL8 did not vary between the two forms. No significant changes were observed between the various forms of Rs.892066 variant and FBG, LDL or HDL. CONCLUSION: Our data shows for the first time that heterozygote form of ANGPTL8 Rs.2278426 variant was associated with higher FBG level in Arabs highlighting the importance of these variants in controlling the function of betatrophin. PMID- 26864935 TI - Impact of Bevacizumab on parenchymal damage and functional recovery of the liver in patients with colorectal liver metastases. AB - BACKGROUND: Little is known about the safety of the anti-VEGF antibody bevacizumab in patients undergoing resection for colorectal liver metastases (CLM). This meta-analysis evaluates the impact of bevacizumab on parenchymal damage and functional recovery in patients undergoing resection for CLM. METHODS: The Medline, Embase and Cochrane Library were systematically searched for studies on preoperative chemotherapy with and without bevacizumab prior to resection of CLM. Studies that reported histological and/or clinical outcomes were eligible for inclusion. Meta-analyses were performed using a random effects model. RESULTS: A total of 18 studies with a total sample size of 2430 patients (1050 patients with bevacizumab) were found. Meta-analyses showed a significant reduction in sinusoidal obstruction syndrome (SOS) (Odds ratio 0.50 [95% confidence interval 0.37, 0.67]; p < 0.001; I(2) = 0%) and hepatic fibrosis (0.61 [0.4, 0.86]; p = 0.004; I(2) = 7%) after preoperative chemotherapy with bevacizumab. The reduced incidence of posthepatectomy liver failure in patients with bevacizumab treatment just failed to reach statistical significance (0.61 [0.34, 1.07]; p = 0.08 I(2) = 6%). While there was no difference in perioperative morbidity and mortality, the incidence of wound complications was significantly increased in patients who received bevacizumab (1.81 [1.12, 2.91]; p = 0.02 I(2) = 4%). CONCLUSIONS: The combination of bevacizumab with cytotoxic chemotherapy is safe but increases the incidence of wound complications after resection of CLM. The reduction of SOS and hepatic fibrosis warrant further investigation and may explain the inverse association of bevacizumab administration and posthepatectomy liver failure. PMID- 26864936 TI - Tgf-beta, Notch, and HGF weave a tangled web of kidney repair. PMID- 26864938 TI - FGF23 from bench to bedside. AB - There is a strong association between elevated circulating fibroblast growth factor-23 (FGF23) levels and adverse outcomes in patients with chronic kidney disease (CKD) of all stages. Initially discovered as a regulator of phosphate and vitamin D homeostasis, FGF23 has now been implicated in several pathophysiological mechanisms that may negatively impact the cardiovascular and renal systems. FGF23 is purported to have direct (off-target) effects in the myocardium, as well as canonical effects on FGF receptor/alpha-klotho receptor complexes in the kidney to activate the renin-angiotensin-aldosterone system, modulate soluble alpha-klotho levels, and increase sodium retention, to cause left ventricular hypertrophy (LVH). Conversely, FGF23 could be an innocent bystander produced in response to chronic inflammation or other processes associated with CKD that cause LVH and adverse cardiovascular outcomes. Further exploration of these complex mechanisms is needed before modulation of FGF23 can become a legitimate clinical target in CKD. PMID- 26864937 TI - Augmentation of angiotensinogen expression in the proximal tubule by intracellular angiotensin II via AT1a/MAPK/NF-kB signaling pathways. AB - Long-term angiotensin II (ANG II) infusion significantly increases ANG II levels in the kidney through two major mechanisms: AT1 receptor-mediated augmentation of angiotensinogen (AGT) expression and uptake of circulating ANG II by the proximal tubules. However, it is not known whether intracellular ANG II stimulates AGT expression in the proximal tubule. In the present study, we overexpressed an intracellular cyan fluorescent ANG II fusion protein (Ad-sglt2-ECFP/ANG II) selectively in the proximal tubule of rats and mice using the sodium and glucose cotransporter 2 (sglt2) promoter. AGT mRNA and protein expression in the renal cortex and 24-h urinary AGT excretion were determined 4 wk following overexpression of ECFP/ANG II in the proximal tubule. Systolic blood pressure was significantly increased with a small antinatriuretic effect in rats and mice with proximal tubule-selective expression of ECFP/ANG II (P < 0.01). AGT mRNA and protein expression in the cortex were increased by >1.5-fold and 61 +/- 16% (P < 0.05), whereas urinary AGT excretion was increased from 48.7 +/- 5.7 (n = 13) to 102 +/- 13.5 (n = 13) ng/24 h (P < 0.05). However, plasma AGT, renin activity, and ANG II levels remained unaltered by ECFP/ANG II. The increased AGT mRNA and protein expressions in the cortex by ECFP/ANG II were blocked in AT1a-knockout (KO) mice. Studies in cultured mouse proximal tubule cells demonstrated involvement of AT1a receptor/MAP kinases/NF-kB signaling pathways. These results indicate that intracellular ANG II stimulates AGT expression in the proximal tubules, leading to increased AGT formation and secretion into the tubular fluid, which contributes to ANG II-dependent hypertension. PMID- 26864939 TI - Inflammatory reaction to fish oil coated polypropylene mesh used for laparoscopic incisional hernia repair: a case report. AB - BACKGROUND: Polypropylene meshes are widely used in hernia repairs. Hernia meshes have been developed incorporating coatings of active agents. One commercially available mesh has a fish oil coating which is promoted as having anti inflammatory properties. We report a case, a symptomatic foreign body granuloma reaction associated with a fish oil coated polypropylene mesh, which required eventual mesh explantation. CASE PRESENTATION: A 61-year old lady with previous peptic ulcer disease underwent a laparoscopic intraperitoneal placement of mesh for incisional hernia utilising a fish oil coated polypropylene mesh. The patient presented 3 months after the procedure complaining of dyspepsia and pain at the operative site. There was no discharge. The patient was managed conservatively. She presented 10 months post-operatively with progressively worsening symptoms and a hard palpable mass in the epigastrium. Abdominal laparoscopy revealed dense adhesive disease around the mesh with exudates. Adhesiolysis, mesh explantation and a partial gastrectomy was performed. Histopathological examination revealed a foreign body granuloma formation to the mesh. CONCLUSION: In-vivo studies looking at intraperitoneal mesh placement with fish oil coatings including data on surgical outcomes such as fistula and adhesive characteristics are scarce in the literature. Further monitoring and studies are required to investigate the safety and efficacy profile of this mesh type in in-vivo models. PMID- 26864940 TI - Healthcare resource use and costs associated with renal impairment in US patients with bone metastases from solid tumors. AB - Introduction During cancer progression, more than half of patients develop renal insufficiency, including chronic kidney disease. The primary and secondary objectives of this study were to estimate healthcare resource use and costs, respectively, associated with renal impairment in patients with bone metastases from solid tumors in the United States. Methods and materials This was a retrospective, observational cohort study conducted using administrative claims data for individuals with solid tumors and bone metastases. Control patients were matched to renal impairment patients using propensity scores (ratio up to 3:1) based on demographics, clinical characteristics, and baseline costs. Average per patient per-year healthcare resource utilization and costs (total costs and cost components; 2013 dollars) were reported. Results In total, 2616 renal impairment patients were matched to 7211 control patients. Renal impairment patients had greater healthcare resource use compared with controls, including a greater mean number of hospital admissions (4.4 versus 2.1), longer average stay per hospital admission (7.4 versus 6.5 days), as well as greater mean number of physician office visits (22.9 versus 18.8), emergency department visits (3.1 versus 2.0), and hospital-based outpatient visits (18.8 versus 16.0) compared with control patients. Total costs were > $50,000 higher among renal impairment patients ($142,267 versus $88,839; P < 0.001), with hospital costs accounting for $72,557 for renal impairment patients, and $27,858 for control patients ( P < 0.001). Conclusion The healthcare resource use and costs associated with renal impairment in patients with bone metastases from solid tumors is high; efforts to reduce renal impairment in this population, including the potential avoidance of nephrotoxic agents, are warranted. PMID- 26864941 TI - Antibacterial and Antibiofilm Effects of Boron on Different Bacteria. AB - Boron (B) compounds are used in many fields ranging from medicine to industry. In this study, boric acid (BA) and disodium octaborate tetrahydrate (DOT) were evaluated for their antibacterial effects and antibiofilm capacities on selected strains of clinical and type cultures that are of veterinary concern (Staphylococcus aureus ATCC 25923, Aeromonas hydrophila ATCC 19570, Pseudomonas aeruginosa ATCC 27853, Brucella melitensis Rev1 and field isolates of Vibrio anguillarum, Aeromonas hydrophila, Yersinia ruckeri, Pseudomonas aeruginosa, Lactococcus garvieae, and Brucella abortus). Also, the inhibition of biofilm was monitored by scanning electron microscopy. The lowest MIC values of BA and DOT were measured, by broth method using microdilution, from Pseudomonas aeruginosa ATCC 27853, and were 0.385 and 0.644 mg/ml, respectively. Staphylococcus aureus was the most resistant to both BA and DOT. Using the microplate method, we observed that the strongest positivities for biofilm production were presented by Pseudomonas aeruginosa ATCC 27853 and also a clinical isolate of Lactococcus garviea. Lower values in the MIC scores for both B compounds were tested by measuring the inhibitory effect on biofilm production. We found that all the bacterial strains inhibited biofilm formation with the exception of the Pseudomonas aeruginosa strains for BA only and an isolate of Lactococcus garviea for DOT only. Such effects by BA and DOT are worth discussing in order to find novel approaches for different functions in medicine and industry using the bacteria tested. PMID- 26864942 TI - What is an evidence map? A systematic review of published evidence maps and their definitions, methods, and products. AB - BACKGROUND: The need for systematic methods for reviewing evidence is continuously increasing. Evidence mapping is one emerging method. There are no authoritative recommendations for what constitutes an evidence map or what methods should be used, and anecdotal evidence suggests heterogeneity in both. Our objectives are to identify published evidence maps and to compare and contrast the presented definitions of evidence mapping, the domains used to classify data in evidence maps, and the form the evidence map takes. METHODS: We conducted a systematic review of publications that presented results with a process termed "evidence mapping" or included a figure called an "evidence map." We identified publications from searches of ten databases through 8/21/2015, reference mining, and consulting topic experts. We abstracted the research question, the unit of analysis, the search methods and search period covered, and the country of origin. Data were narratively synthesized. RESULTS: Thirty-nine publications met inclusion criteria. Published evidence maps varied in their definition and the form of the evidence map. Of the 31 definitions provided, 67 % described the purpose as identification of gaps and 58 % referenced a stakeholder engagement process or user-friendly product. All evidence maps explicitly used a systematic approach to evidence synthesis. Twenty-six publications referred to a figure or table explicitly called an "evidence map," eight referred to an online database as the evidence map, and five stated they used a mapping methodology but did not present a visual depiction of the evidence. CONCLUSIONS: The principal conclusion of our evaluation of studies that call themselves "evidence maps" is that the implied definition of what constitutes an evidence map is a systematic search of a broad field to identify gaps in knowledge and/or future research needs that presents results in a user-friendly format, often a visual figure or graph, or a searchable database. Foundational work is needed to better standardize the methods and products of an evidence map so that researchers and policymakers will know what to expect of this new type of evidence review. SYSTEMATIC REVIEW REGISTRATION: Although an a priori protocol was developed, no registration was completed; this review did not fit the PROSPERO format. PMID- 26864943 TI - Intramolecular Hydrogen Bonds in Low-Molecular-Weight Polyethylene Glycol. AB - We used static DFT calculations to analyze, in detail, the intramolecular hydrogen bonds formed in low-molecular-weight polyethylene glycol (PEG) with two to five repeat subunits. Both red-shifted O-H???O and blue-shifting C-H???O hydrogen bonds, which control the structural flexibility of PEG, were detected. To estimate the strength of these hydrogen bonds, the quantum theory of atoms in molecules was used. Car-Parrinello molecular dynamics simulations were used to mimic the structural rearrangements and hydrogen-bond breaking/formation in the PEG molecule at 300 K. The time evolution of the H???O bond length and valence angles of the formed hydrogen bonds were fully analyzed. The characteristic hydrogen-bonding patterns of low-molecular-weight PEG were described with an estimation of their lifetime. The theoretical results obtained, in particular the presence of weak C-H???O hydrogen bonds, could serve as an explanation of the PEG structural stability in the experimental investigation. PMID- 26864944 TI - Enhancer RNA-driven looping enhances the transcription of the long noncoding RNA DHRS4-AS1, a controller of the DHRS4 gene cluster. AB - The human DHRS4 gene cluster consists of DHRS4 and two immediately downstream homologous genes, DHRS4L2 and DHRS4L1, generated by evolutionarily gene duplication events. We previously demonstrated that a head-to-head natural antisense transcript (NAT) of DHRS4, denoted DHRS4-AS1, regulates all three genes of the DHRS4 gene cluster. However, it is puzzling that DHRS4L2 and DHRS4L1 did not evolve their own specific NATs to regulate themselves, as it seems both have retained sequences highly homologous to DHRS4-AS1. In a search of the DHRS4-AS1 region for nearby enhancers, we identified an enhancer located 13.8 kb downstream of the DHRS4-AS1 transcriptional start site. We further showed, by using a chromosome conformation capture (3C) assay, that this enhancer is capable of physically interacting with the DHRS4-AS1 promoter through chromosomal looping. The enhancer produced an eRNA, termed AS1eRNA, that enhanced DHRS4-AS1 transcription by mediating the spatial interactions of the enhancer and DHRS4-AS1 promoter in cooperation with RNA polymerase II and p300/CBP. Moreover, the distributions of activating acetyl-H3 and H3K4me3 modifications were found to be greater at the DHRS4-AS1 promoter than at the homologous duplicated regions. We propose that AS1eRNA-driven DNA looping and activating histone modifications promote the expression of DHRS4-AS1 to economically control the DHRS4 gene cluster. PMID- 26864945 TI - Anticancer efficacy of a nitric oxide-modified derivative of bifendate against multidrug-resistant cancer cells. AB - The development of multidrug resistance (MDR) not only actively transports a wide range of cytotoxic drugs across drug transporters but is also a complex interaction between a number of important cellular signalling pathways. Nitric oxide donors appear to be a new class of anticancer therapeutics for satisfying all the above conditions. Previously, we reported furoxan-based nitric oxide releasing compounds that exhibited selective antitumour activity in vitro and in vivo. Herein, we demonstrate that bifendate (DDB)-nitric oxide, a synthetic furoxan-based nitric oxide-releasing derivative of bifendate, effectively inhibits the both sensitive and MDR tumour cell viability at a comparatively low concentration. Interestingly, the potency of DDB-nitric oxide is the independent of inhibition of the functions and expressions of three major ABC transporters. The mechanism of DDB-nitric oxide appears to be in two modes of actions by inducing mitochondrial tyrosine nitration and apoptosis, as well as by down regulating HIF-1alpha expression and protein kinase B (AKT), extracellular signal regulated kinases (ERK), nuclear factor kappaB (NF-kappaB) activation in MDR cells. Moreover, the addition of a typical nitric oxide scavenger significantly attenuated all the effects of DDB-nitric oxide, indicating that the cytotoxicity of DDB-nitric oxide is as a result of higher levels of nitric oxide release in MDR cancer cells. Given that acquired MDR to nitric oxide donors is reportedly difficult to achieve and genetically unstable, compound like DDB-nitric oxide may be a new type of therapeutic agent for the treatment of MDR tumours. PMID- 26864946 TI - Use of whole-genome sequencing to trace, control and characterize the regional expansion of extended-spectrum beta-lactamase producing ST15 Klebsiella pneumoniae. AB - The study describes the transmission of a CTX-M-15-producing ST15 Klebsiella pneumoniae between patients treated in a single center and the subsequent inter institutional spread by patient referral occurring between May 2012 and September 2013. A suspected epidemiological link between clinical K. pneumoniae isolates was supported by patient contact tracing and genomic phylogenetic analysis from May to November 2012. By May 2013, a patient treated in three institutions in two cities was involved in an expanding cluster caused by this high-risk clone (HiRiC) (local expansion, CTX-M-15 producing, and containing hypervirulence factors). A clone-specific multiplex PCR was developed for patient screening by which another patient was identified in September 2013. Genomic phylogenetic analysis including published ST15 genomes revealed a close homology with isolates previously found in the USA. Environmental contamination and lack of consistent patient screening were identified as being responsible for the clone dissemination. The investigation addresses the advantages of whole-genome sequencing in the early detection of HiRiC with a high propensity of nosocomial transmission and prolonged circulation in the regional patient population. Our study suggests the necessity for inter-institutional/regional collaboration for infection/outbreak management of K. pneumoniae HiRiCs. PMID- 26864948 TI - Endovascular Interventional Cardiology: 2015 in Review. AB - Minimally invasive interventional procedures have become an appealing option for patients with endovascular disease historically referred to surgery. This article reviews the major advancements and trials published in 2015. PMID- 26864947 TI - Changes of sperm quality and hormone receptors in the rat testis after exposure to methamphetamine. AB - Methamphetamine (METH) is known to damage neurons and induce psychosis. It can also induce apoptosis in seminiferous tubules and affect sperm quality. The present study was carried out to investigate the effect of a rat model of METH addiction on sperm quality and expression of progesterone receptors (PR) and estrogen receptors (ER) in the testis. Sperm quality parameters including sperm motility, sperm morphology and sperm concentration were examined. Protein and gene expressions PR, ERalpha and ERbeta were studied using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. The percentages of normal sperm motility and normal sperm morphology were significantly decreased in animals receiving METH, especially in escalating dose (ED METH) and escalating dose-binge (ED-binge METH) groups when compared with control. In addition, sperm concentrations in ED METH and ED-binge METH groups were numerically decreased. PR, ERalpha and ERbeta immunoreactive cells were significantly decreased in spermatogonia, spermatogenic cells and especially in Sertoli cells in all METH-treated groups. Furthermore, messenger RNA expression of PR, ERalpha and ERbeta were also significantly decreased in all METH-treated animals. These results indicate that METH can induce abnormal sperm quality. These changes of sperm quality may relate to the reduction of PR, ERalpha and ERbeta expressions in male germ cells and Sertoli cells which are essential for spermatogenesis and development of sperm. PMID- 26864949 TI - Percutaneous Coronary Intervention: 2015 in Review. AB - In order to keep the interventional community up-to-date with the overwhelming amount of new data, we have selected where we believe to be the most important publications in percutaneous coronary intervention from January 1, 2015 to mid November 2015. We hope that this will serve as an important overview of 2015, and ongoing reference for future years. PMID- 26864950 TI - Transcatheter Aortic Valve Replacement: 2015 in Review. AB - Transcatheter aortic valve replacement (TAVR) has emerged as an attractive option for patients with severe symptomatic aortic stenosis (AS) who are either at high risk or extreme risk for surgical aortic valve replacement (SAVR). This article summarizes the major advances in TAVR that were published or reported in 2015. PMID- 26864951 TI - Long Coronary Lesions Treated With Thin Strut Bioresorbable Polymer Drug Eluting Stent: Experience From Multicentre Randomized CENTURY II Study. AB - OBJECTIVES: To assess performance of new, bioresorbable polymer sirolimus-eluting stent (BP-SES), in patients with long coronary lesions (LL) and to compare it to permanent polymer everolimus-eluting stent (PP-EES). BACKGROUND: LL have been associated with worse clinical outcomes in percutaneous coronary interventions (PCI). The impact of lesion length on the outcomes of drug eluting stent (DES) implantations is not as clear. METHODS: In the frame of a randomized, multicentre CENTURY II study, out of 1119 patients enrolled, 182 patients had LL (defined as >=25 mm), and were assigned randomly to treatment with BP-SES (101) or PP-EES (81). Primary endpoint was target lesion failure (TLF, composite of cardiac death, target vessel related myocardial infarction [MI], and target lesion revascularization [TLR]) at 9 months. All data were 100% monitored and adverse events were adjudicated by an independent clinical event committee. RESULTS: The baseline patient and lesion characteristics were similar in the 2 study arms. At 9-months, the rates of cardiac death (2.0% vs 1.2%; P = 0.70), MI (3.0% vs 4.9%; P = 0.49) and clinically driven TLR (2.0% vs 3.7%; P = 0.48) and TLF (6.9% vs 8.6%; P = 0.67) were similar for BP-SES and PP-EES, respectively. There was no stent thrombosis (ST) in BP-SES group up to 9 months, while 1 case (1.2%) of ST was recorded in PP-EES group (P = 0.44). CONCLUSIONS: Patients with LL showed similar clinical outcomes when treated with Ultimaster BP-SES and Xience PP-EES. PMID- 26864953 TI - A Comparison of Intravascular Imaging Modalities for Detection of Stent Struts in Acute Coronary Syndrome. AB - BACKGROUND: We used optical coherence tomography (OCT) and intravascular ultrasound (IVUS) to assess the struts of implanted stents in patients with acute coronary syndrome (ACS). METHODS: A totle of 10,756 stent struts were analyzed with OCT in 42 patients of ACS. Of them, both of IVUS and OCT imaging were performed in 33 patients. Appearance of stent struts was classified as well apposed, buried, malapposed, and nondetectable, and the number of stent struts were counted by OCT and IVUS was compared. RESULTS: Most of stent struts were well apposed (78.1%, 8,407/10,756). However, malapposed struts were 5.6% (607/10,756), and 14.1% (1,514/10,756) of stent struts were buried by thrombus. The nondetectable struts were 2.11% (228/10,756) in ACS. 94.7% (216/228) of nondetectable stent struts were associated with red thrombus, and plaque prolapse was in 5.3% (12/228). The number of stent struts counted by OCT were larger than that of IVUS. The mean number of stent struts at the proximal and distal stent edges were 24 +/- 6.57 in OCT, the stent struts IVUS counted were 20 +/- 4.18 (P < 0.0001). Although the frequency of malapposed struts were similar 4.6% (376/8,248) in OCT versus 4.8% (369/7,674) in IVUS (P = 0.788). Stent struts were often buried by thrombus in ACS 15.2% (1,252/8,248) in OCT versus 9.7% (747/7,674) in IVUS; P = 0.006. The nondetectable struts were fewer in IVUS than OCT 0.2% (16/7,674) in IVUS versus 2.2% (187/8,248) in OCT; P < 0.0001. CONCLUSION: Stent struts are frequently buried and nondetectable due to thrombi burden in ACS patients. Adequate thrombus removal and proper selection of the imaging device is warranted in ACS. PMID- 26864952 TI - Circulating Endothelial Cells and Endothelial Function Predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction. AB - Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major adverse cardiac events (MACE) consisting of all-cause mortality, recurrent nonfatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), von Willebrand factor (vWF) level (P = 0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82, respectively, for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (P = 0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID- 26864954 TI - Structure and flow of dense suspensions of protein fractal aggregates in comparison with microgels. AB - Solutions of the globular whey protein beta-lactoglobulin (beta-lg) were heated at different protein concentrations leading to the formation of polydisperse fractal aggregates with different average sizes. The structure of the solutions was analyzed with light scattering as a function of the protein concentration. The osmotic compressibility and the dynamic correlation length decreased with increasing concentration and became independent of the aggregate size in dense suspensions. The results obtained for different aggregate sizes could be superimposed after normalizing the concentration with the overlap concentration. Dense suspensions of fractal protein aggregates are strongly interpenetrated and can be visualized as an ensemble of fractal 'blobs'. The viscosity of the heated beta-lg solutions increased extremely sharply above 80 g L(-1) and diverged at 98 g L(-1), mainly due to the sharply increasing aggregate size. At a fixed aggregate size, the viscosity increased initially exponentially with increasing concentration and then diverged. The increase was stronger when the aggregates were larger, but the dependence of the viscosity on the aggregate size was weaker than that of the osmotic compressibility and the dynamic correlation length. The concentration dependence of the viscosity of solutions of fractal beta-lg aggregates is much stronger than that of homogeneous beta-lg microgels. The behavior of fractal aggregates formed by whey protein isolates was similar. PMID- 26864955 TI - Authors' reply to Gotzsche and Hamilton. PMID- 26864958 TI - Research Gaps in the Use of Dairy Ingredients in Food Aid Products. AB - BACKGROUND: Nutritional interventions to help prevent stunting, particularly in the first 1000 days from conception to 2 years of a child's life, are a major focus of numerous food aid organizations worldwide. Dairy ingredients can play an important role in enhancing the nutritional value and effectiveness of food products used in food aid. OBJECTIVE: This article addresses gaps in research on malnutrition from both a broad perspective and specific to dairy ingredients. METHODOLOGY: Narrative review. RESULTS AND CONCLUSIONS: From a broad perspective, there is a need for gaining a consensus by the research community and funders of research on best practices for protocol development, outcomes measured, and reporting of study outcomes. Identification of biomarkers and rapid screening methods and consistent application of their use would expedite future research. A better understanding of nutritional requirements for malnourished populations, including the effects of energy deficits and disease on those requirements, is needed. More specific to dairy ingredients, a key research question is: Does dairy protein or the package of nutrients provided by dairy ingredients have a unique impact on growth, and if so, how? Also, data on the optimal levels of dairy ingredients based on the effective cost of treatment are needed, particularly in the treatment and prevention of moderate acute malnutrition and during pregnancy. PMID- 26864957 TI - Optimizing Ready-to-Use Therapeutic Foods for Protein Quality, Cost, and Acceptability. AB - This article describes current research on the development of alternative ready to-use therapeutic foods (RUTFs) in the treatment of severe acute malnutrition. An innovative and versatile linear programming tool has been developed to facilitate the creation of therapeutic formulas that are determined acceptable on multiple levels: costs, ingredient acceptability, availability and stability, nutrient requirements, and personal preferences. The formulas are analyzed for ease of production by Washington University team members and for organoleptic properties acceptability to target populations. In the future, RUTF products that are cost-effective, acceptable, sustainable, and widely available will become a reality. PMID- 26864959 TI - Ready-to-Use Supplementary Foods and Ready-to-Use Therapeutic Foods: Developing Product Standards. AB - The purpose of this commentary is to describe the current regulatory environment for the multitude of ready-to-use supplementary foods and ready-to-use therapeutic foods used in international feeding programs for undernourished and malnourished children. A perspective on the role of standards, their desirable scope, benefits and limitations as well as possible future developments of products in these categories also is provided. PMID- 26864956 TI - The role of Orai-STIM calcium channels in melanocytes and melanoma. AB - Calcium signalling within normal and cancer cells regulates many important cellular functions such as migration, proliferation, differentiation and cytokine secretion. Store operated Ca(2+) entry (SOCE) via the Ca(2+) release activated Ca(2+) (CRAC) channels, which are composed of the plasma membrane based Orai channels and the endoplasmic reticulum stromal interaction molecules (STIMs), is a major Ca(2+) entry route in many cell types. Orai and STIM have been implicated in the growth and metastasis of multiple cancers; however, while their involvement in cancer is presently indisputable, how Orai-STIM-controlled Ca(2+) signals affect malignant transformation, tumour growth and invasion is not fully understood. Here, we review recent studies linking Orai-STIM Ca(2+) channels with cancer, with a particular focus on melanoma. We highlight and examine key molecular players and the signalling pathways regulated by Orai and STIM in normal and malignant cells, we expose discrepancies, and we reflect on the potential of Orai-STIMs as anticancer drug targets. Finally, we discuss the functional implications of future discoveries in the field of Ca(2+) signalling. PMID- 26864961 TI - Microcephaly in Brazil: how to interpret reported numbers? PMID- 26864960 TI - Obesity and hypercholesterolemia in patients with prolactinomas: Could DHEA-S and growth hormone be the missing link? AB - PURPOSE: Increasing evidence exists that hyperprolactinemia alters metabolic profile. The mechanism of this effect is unknown. We aimed to investigate the differences between the metabolic profile of patients with prolactinomas and nonfunctional pituitary adenomas and to evaluate the impact of other pituitary hormones on their metabolic profile. METHODS: Our retrospective study included 86 consecutive patients with prolactinomas and nonfunctional adenomas (29 prolactinomas and 57 adenomas). Body mass index (BMI), blood pressure, serum prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), adrenocorticotropic hormone (ACTH), cortisol, urinary free cortisol, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), testosterone in men, triglycerides, total cholesterol, HDL (high-density lipoprotein) cholesterol, LDL (Low-density lipoprotein) cholesterol, alanine-transaminase, aspartate-transaminase, fasting glucose, and C-reactive protein (CRP) were obtained for all patients. Regression analyses were performed on log-transformed data. RESULTS: After adjustment for age, gender, and tumor size, prolactinomas were associated with higher BMI (OR 5.61, 95%CI 1.70-9.51, p = 0.005), LDL cholesterol (OR 3.60, 95%CI 1.35-5.93, p = 0.015), DHEA-S (OR 1.97, 95%CI 1.23-3.72, p = 0.026), and lower GH levels (OR 0.43, 95%CI 0.03-0.84, p = 0.037). In a linear multivariate regression, the association between DHEA-S, GH, and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin. CONCLUSIONS: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed. PMID- 26864962 TI - A crucial time for public health preparedness: Zika virus and the 2016 Olympics, Umrah, and Hajj. PMID- 26864963 TI - Graphitic carbon nitride "reloaded": emerging applications beyond (photo)catalysis. AB - Despite being one of the oldest materials described in the chemical literature, graphitic carbon nitride (g-C3N4) has just recently experienced a renaissance as a highly active photocatalyst, and the metal-free polymer was shown to be able to generate hydrogen under visible light. The semiconductor nature of g-C3N4 has triggered tremendous endeavors on its structural manipulation for enhanced photo(electro)chemical performance, aiming at an affordable clean energy future. While pursuing the stem of g-C3N4 related catalysis (photocatalysis, electrocatalysis and photoelectrocatalysis), a number of emerging intrinsic properties of g-C3N4 are certainly interesting, but less well covered, and we believe that these novel applications outside of conventional catalysis can be favorably exploited as well. Thanks to the general efforts devoted to the exploration and enrichment of g-C3N4 based chemistry, the boundaries of this area have been possibly pushed far beyond what people could imagine in the beginning. This review strives to cover the achievements of g-C3N4 related materials in these unconventional application fields for depicting the broader future of these metal-free and fully stable semiconductors. This review starts with the general protocols to engineer g-C3N4 micro/nanostructures for practical use, and then discusses the newly disclosed applications in sensing, bioimaging, novel solar energy exploitation including photocatalytic coenzyme regeneration, templating, and carbon nitride based devices. Finally, we attempt an outlook on possible further developments in g-C3N4 based research. PMID- 26864965 TI - A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification. AB - During development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE-1 silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we found that REST knockout cells lost the ability to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective downregulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals. REST regulates cardiac differentiation of ESCs by negatively regulating the Wnt/beta-catenin signaling pathway and positively regulating the cardiogenic TF Gata4. We propose here a new role for REST in cell fate specification besides its well-known repressive role of neuronal differentiation. PMID- 26864964 TI - Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus. AB - Calcineurin heterodimer, comprised of the catalytic (CnaA) and regulatory (CnaB) subunits, localizes at the hyphal tips and septa to direct growth, septation, and disease in the human pathogen Aspergillus fumigatus. Here we discovered a novel motif (FMDVF) required for this critical CnaA septal localization, including residues Phe368, Asp370 and Phe372 overlapping the cyclosporine A-cyclophilin A binding domain, CnaB-binding helix and the FK506-FKBP12-binding pocket. Mutations in adjacent residues Asn367, Trp374, and Ser375 confer FK506 resistance without impacting CnaA septal localization. Modeling A. fumigatus CnaA confirmed that the FMDVF motif forms a bridge between the two known substrate-binding motifs, PxIxIT and LxVP, and concurrent mutations (F368A D370A; F368A F372A) in the FMDVF motif disrupt CnaA-substrate interaction at the septum. PMID- 26864966 TI - Time course, outcome and management of adverse drug reactions associated with metformin from patient's perspective: a prospective, observational cohort study in the Netherlands. AB - PURPOSE: The aim of this study was to gather information about frequency, latency time, outcome and management of frequently occurring adverse drug reactions (ADRs) related to the use of metformin in daily practice. METHODS: A prospective, observational cohort study was performed. A total of 2490 first-time metformin users were recruited through pharmacies in the Netherlands between February 1, 2008, and April 1, 2012. Patients were invited to complete six web-based questionnaires at 2-week, 6-week, 3-month, 6-month, 9-month and 12-month intervals after starting treatment with metformin. Information was gathered about patient characteristics, ADRs and drug use. RESULTS: The occurrence of at least one possible ADR related to the use of metformin was reported by 34.5 % of the patients. A higher proportion of females reported the occurrence of an ADR (39.6 %) compared to the proportion in males (30.9 %). Some patients (11.4 %) stopped using metformin within 1 year after start. More than half of the patients (50.8 %) undertook no action regarding metformin after the occurrence of ADRs. A high number of patients (77.7 %) recovered or were still recovering from ADRs despite continuation of metformin. Most ADRs occurred shortly after the beginning of the treatment, with a median latency time of 1-6 days. The study revealed some ADR specific differences in occurrence rate, latency time, management and outcome. CONCLUSION: This study successfully obtained information about frequency, latency time, outcome and management of frequently occurring ADRs related to the use of metformin in daily practise. PMID- 26864967 TI - Possible isomers in ligand protected Ag11 cluster ions identified by ion mobility mass spectrometry and fragmented by surface induced dissociation. AB - This communication reports the identification of gas phase isomers in monolayer protected silver clusters. Two different isomers of Ag11(SG)7(-) (SG-gulathione thiolate) with different drift times have been detected using combined electrospray ionization (ESI) and ion mobility (IM) mass spectrometry (MS). Surface induced dissociation (SID) of the 3(-) charge state of such clusters shows charge stripping to give the 1(-) charged ion with some sodium attachment, in addition to fragmentation. SID and collision induced dissociation (CID) for Ag11(SG)7(-) suggest different pathways being accessed with each method. SID was introduced for the first time for the study of monolayer-protected clusters. PMID- 26864968 TI - Ultra-high-throughput Production of III-V/Si Wafer for Electronic and Photonic Applications. AB - Si-based integrated circuits have been intensively developed over the past several decades through ultimate device scaling. However, the Si technology has reached the physical limitations of the scaling. These limitations have fuelled the search for alternative active materials (for transistors) and the introduction of optical interconnects (called "Si photonics"). A series of attempts to circumvent the Si technology limits are based on the use of III-V compound semiconductor due to their superior benefits, such as high electron mobility and direct bandgap. To use their physical properties on a Si platform, the formation of high-quality III-V films on the Si (III-V/Si) is the basic technology ; however, implementing this technology using a high-throughput process is not easy. Here, we report new concepts for an ultra-high-throughput heterogeneous integration of high-quality III-V films on the Si using the wafer bonding and epitaxial lift off (ELO) technique. We describe the ultra-fast ELO and also the re-use of the III-V donor wafer after III-V/Si formation. These approaches provide an ultra-high-throughput fabrication of III-V/Si substrates with a high-quality film, which leads to a dramatic cost reduction. As proof-of concept devices, this paper demonstrates GaAs-based high electron mobility transistors (HEMTs), solar cells, and hetero-junction phototransistors on Si substrates. PMID- 26864969 TI - Polymeric check valve with an elevated pedestal for precise cracking pressure in a glaucoma drainage device. AB - This paper presents the design, fabrication, and characterization of a polymeric micro check valve for a glaucoma drainage device (GDD) featuring the precise regulation of intraocular pressure (IOP) and effective aqueous humor turnover (AHT). The pedestal, slightly elevated by selective coating of a parylene C film, induces pre-stress in the thin valve membrane, which enhances the predictability of the cracking pressure of the GDD. The proposed GDD comprises a cannula and a normally closed polymeric micro check valve, which are made of PDMS, a biocompatible polymer, with three layers: top (cover), intermediate (thin valve membrane), and bottom (base plate). A feedback channel, located between the top and intermediate layers, prevents reverse flow by feeding the pressure of the outlet channel back to the thin valve membrane. To achieve a precise cracking pressure and sufficient drainage of humor for humans, the thicknesses of the valve membrane and parylene C film are designed to be 58 MUm and 1 MUm, respectively, which are confirmed using a COMSOL simulation. The experimental results show that the cracking pressure of the fabricated GDD lies within the range of normal IOP (1.33-2.67 kPa). The forward flow rate (drainage rate), 4.3 +/- 0.9 MUL/min at 2.5 kPa, is adequate to accommodate the rate of AHT in a normal human eye (2.4 +/- 0.6 MUL/min). The reverse flow was not observed when a hydrostatic pressure of up to 4 kPa was applied to the outlet and the feedback channel. PMID- 26864970 TI - A concentration gradient generator on a paper-based microfluidic chip coupled with cell culture microarray for high-throughput drug screening. AB - Inspired by the paper platforms for 3-D cell culture, a paper-based microfluidic device containing drug concentration gradient was designed and constructed for investigating cell response to drugs based on high throughput analysis. This drug gradient generator was applied to generate concentration gradients of doxorubicin (DOX) as the model drug. HeLa cells encapsulated in collagen hydrogel were incubated in the device reservoirs to evaluate the cell viability based on the controlled release of DOX spatially. It was demonstrated that drug diffusion through the paper fibers created a gradient of drug concentration, which influenced cell viability. This drug screening platform has a great opportunity to be applied for drug discovery and diagnostic studies with simultaneous and parallel tests of drugs under various gradient concentrations. PMID- 26864971 TI - Patients' expectations and experiences of epilepsy surgery--A population-based long-term qualitative study. AB - OBJECTIVE: The aim of this prospective and population-based longitudinal study was to explore patients' expectations before surgery and their experiences both short and long term after epilepsy surgery. METHODS: A national sample of adult patients answered open-ended questions preoperatively, 2 years after surgery and at a cross-sectional long-term follow-up (mean 13 years, standard deviation [SD] 1.85). The answers were analyzed by qualitative content analysis. RESULTS: Eighty patients participated in the study. Before surgery, patients experienced a belief in a "normal" life; they hoped for reduction of seizures and medication, a richer social life, and more self-confidence. However, they also experienced anxiety of the unknown. They were afraid of the operation, of continued seizures, and of complications. At both postoperative follow-ups patients experienced increased independence. They had symptom reduction, felt relief from worries and fears, and felt that they had a new life. However, some patients experienced that the operation had changed their life to the worse due to both psychological and neurologic adverse effects, regardless of whether they had obtained seizure freedom or improvement. SIGNIFICANCE: Positive experiences of epilepsy surgery dominated, both in the short and long term. However, attention must be paid to negative expectations before and negative experiences after surgery in order to provide individual support and information. This should increase the possibility for patients to have realistic hopes before surgery and to find coping strategies in the new life situation after surgery. PMID- 26864973 TI - Biomechanics in vascular biology and cardiovascular disease. PMID- 26864972 TI - Model parameters for simulation of physiological lipids. AB - Coarse grain simulation of proteins in their physiological membrane environment can offer insight across timescales, but requires a comprehensive force field. Parameters are explored for multicomponent bilayers composed of unsaturated lipids DOPC and DOPE, mixed-chain saturation POPC and POPE, and anionic lipids found in bacteria: POPG and cardiolipin. A nonbond representation obtained from multiscale force matching is adapted for these lipids and combined with an improved bonding description of cholesterol. Equilibrating the area per lipid yields robust bilayer simulations and properties for common lipid mixtures with the exception of pure DOPE, which has a known tendency to form nonlamellar phase. The models maintain consistency with an existing lipid-protein interaction model, making the force field of general utility for studying membrane proteins in physiologically representative bilayers. PMID- 26864975 TI - Environmental disturbances and fishes in the Amazon. PMID- 26864976 TI - Highly Efficient Catalysis of Retro-Claisen Reactions: From a Quinone Derivative to Functionalized Imidazolium Salts. AB - A new and efficient method for the preparation of several imidazolium salts containing an ester group in the C4 position of the aromatic ring through a retro Claisen reaction pathway between a quinone derivative and several alcohols is described. This new organic transformation proceeds in the absence of a catalyst, but it is greatly catalyzed by different Lewis acids, especially with AgOAc at a very low catalyst loading and in very short reaction times. The process takes place by the nucleophilic attack of the carbonyl groups by the alcohol functionality, thus promoting a double C-C bond cleavage and C-H and C-O bond formation. This reaction represents the first example of this type between a quinone derivative and alcohols. PMID- 26864974 TI - Epidemiology of sport-related spinal cord injuries: A systematic review. AB - CONTEXT: Despite the recognition of sports as a significant contributor in the etiology of spinal cord injury (SCI), no studies have systematically explored the epidemiology of SCI caused by sports. OBJECTIVE: This paper aims to give a systematic overview of the epidemiology of sport-related spinal cord injury around the world. METHODS: A systematic review was conducted to identify published literature reporting the epidemiology of SCI caused by sports. The literature search was conducted in MEDLINE/PubMed, CINAHL, EMBASE, PsycINFO and Sportdiscus with date limits 1980 through to July 2015. Data from 54 studies covering 25 countries was extracted and collated. RESULTS: Important findings include identification of 6 countries in which sports accounts for over 13% of SCI (highest to lowest: Russia, Fiji, New Zealand, Iceland, France and Canada); individual sports with high risk for SCI (diving, skiing, rugby, and horseback riding); and the most common level of injury for various sports (almost entirely cervical for hockey, skiing, diving and American football, while over half of horseback riding and snowboarding injuries are thoracic or lumbosacral). CONCLUSION: This paper identifies countries and sports with higher rates of sport related SCIs where implementation of prevention programs and reporting systems to track SCI epidemiology may be helpful, and highlights gaps in our current knowledge for further investigation. The comparison of SCI occurrence for each sport across countries, as well as examination of the specific characteristics of SCI incurred for individual sports will assist in directing efforts for prevention. PMID- 26864977 TI - Hb Agenogi [beta90(F6)Glu->Lys (GAG>AAG) HBB: c.271G>A)] in a Pregnant Thai Woman. AB - Hb Agenogi [beta90(F6)Glu->Lys (GAG>AAG) HBB: c.271G>A)] is a very rare beta globin chain variant. We report for the first time this hemoglobinopathy in a pregnant 20-year-old Thai woman. She was seen by an obstetrician at her 14th week of gestation. She was pale and had an inflammatory lesion of her lower left leg. The hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) and low pressure liquid chromatography (LPLC) showed a peak of abnormal Hb at the C window. On capillary electrophoresis (CE), the abnormal Hb peak was observed at electrophoretic zone 4 that corresponded to the Hb E (HBB: c.79G>A) peak. Direct DNA sequencing revealed a GAG>AAG mutation at codon 90 of the beta-globin gene. Thus, even though Hb Agenogi is very rare, it can be found in Thai people. The knowledge and understanding of this hemoglobinopathy will be used to assist in diagnosis, management and counseling for patients. PMID- 26864978 TI - Redox-Switchable Surface Wrinkling on Polyaniline Film. AB - Here the redox-driven switch between the wrinkled and dewrinkled states on poly aniline (PANI) film is reported. This switch is derived from the reversible transition in different intrinsic redox states of polyaniline (e.g., between emeraldine salt (ES) and leucoemeraldine base (LEB) or between ES and pernigraniline base (PB)) that are involved in the redox reaction, coupled with the corresponding volume expansion/shrinkage. Interestingly, the as-wrinkled ES film becomes deswollen and dewrinkled when reduced to the LEB state or oxidized to the PB state. Conversely, oxidation of the LEB film or reduction of the PB film into the swollen ES film leads to the reoccurrence of surface wrinkling. Furthermore, the reducibility of the dewrinkled LEB film and the oxidizability of the dewrinkled PB film are well utilized respectively to yield various wrinkled PANI-based composite films. PMID- 26864979 TI - BEST TEST with MEDIOCRE RESULTS (at best!): a "call to arms" to correct clinician knowledge deficits in transfusion medicine. PMID- 26864980 TI - Consider the source: the importance of including all transfused products and exposures in red blood cell alloimmunization research. PMID- 26864981 TI - Frequent fliers in the reference laboratory. PMID- 26864982 TI - Transfusion medicine illustrated. A complicated case of plasma exchange. PMID- 26864985 TI - Erratum. PMID- 26864986 TI - Life and treatment goals of patients with advanced, incurable cancer. AB - PURPOSE: Goals of care conversations have been suggested as a strategy for helping patients with advanced cancer manage the uncertainty and distress associated with end-of-life care. However, knowledge deficits about patient goals limit the utility of such conversations. We described the life and treatment goals of patients with incurable cancers, including goal values and expectancies. We examined the associations between paramount goals and patient prognosis, performance status, and psychological adjustment. METHODS: Patients with advanced lung cancer, gastrointestinal cancer, or melanoma (N = 84) completed measures of prognosis for 12-month survival, hope, optimism, depression, and anxiety. Oncologists provided patient performance status and prognosis for 12-month survival. We conducted interviews with a subset of patients (N = 63), eliciting life and treatment goals, values, and expectancies. RESULTS: Patient life goals resembled goals among healthy populations; whereas, treatment goals were perceived as separate and more important. Cure and fight cancer emerged as the most important goals. Patients who valued cure the most had worse performance status (M = 1.46 vs. 0.78) and more depressive symptoms (M = 6.30 vs. 3.50). Patients who valued fight cancer the most had worse self-prognosis (M = 69.23 % vs. 86.11 %), fewer treatment goals (M = 2.08 vs. 3.16), and lower optimism (M = 15.00 vs. 18.32). CONCLUSIONS: Patients with advanced cancer perceive treatment goals as separate from and more important than life goals. They hold optimistic expectancies for achieving their goals and for survival. Valuing cure highly may put patients at risk for experiencing psychological maladjustment. PMID- 26864984 TI - Wnt Signaling Inhibition Deprives Small Intestinal Stem Cells of Clonogenic Capacity. AB - The Wnt pathway plays a crucial role in self-renewal and differentiation of cells in the adult gut. In the present study, we revealed the functional consequences of inhibition of canonical Wnt signaling in the intestinal epithelium. The study was based on generation of a novel transgenic mouse strain enabling inducible expression of an N-terminally truncated variant of nuclear Wnt effector T cell factor 4 (TCF4). The TCF4 variant acting as a dominant negative (dn) version of wild-type (wt) TCF4 protein decreased transcription of beta-catenin-TCF4 responsive genes. Interestingly, suppression of Wnt/beta-catenin signaling affected asymmetric division of intestinal stem cells (ISCs) rather than proliferation. ISCs expressing the transgene underwent several rounds of division but lost their clonogenic potential and migrated out of the crypt. Expression profiling of crypt cells revealed that besides ISC-specific markers, the dnTCF4 production downregulated expression levels of epithelial genes produced in other crypt cells including markers of Paneth cells. Additionally, in Apc conditional knockout mice, dnTCF activation efficiently suppressed growth of Apc-deficient tumors. In summary, the generated mouse strain represents a convenient tool to study cell-autonomous inhibition of beta-catenin-Tcf-mediated transcription. PMID- 26864987 TI - Extending health insurance in Ghana: effects of the National Health Insurance Scheme on maternity care. AB - BACKGROUND: There is considerable interest in exploring the potential of social health insurance in Africa where a number of countries are currently experimenting with different approaches. Since these schemes have been introduced recently and are continuously evolving, it is important to evaluate their effectiveness in the enhancement of health care utilization and reduction of out of-pocket expenses for potential policy suggestions. OBJECTIVE: To investigate how the National Health Insurance Schemes (NHIS) in Ghana affects the utilization of maternal health care services and medical out-of-pocket expenses. METHODS: We used nationally-representative household data from the Ghana Demographic and Health Survey (GDHS). We analyzed the 2014 GDHS focusing on four outcome variables, i.e. antenatal check up, delivery in a health facility, delivery assisted by a trained person and out-of-pocket expenditure. We estimated probit and bivariate probit models to take into account the issue of self selection into the health insurance schemes. RESULTS: The results suggest that, also taking into account the issue of self selection into the health insurance schemes, the NHIS enrollment positively affects the probability of formal antenatal check-ups before delivery, the probability of delivery in an institution and the probability of being assisted during delivery by a trained person. On the contrary, we find that, once the issue of self-selection is taken into account, the NHIS enrollment does not have a significant effect on out-of-pocket expenditure at the extensive margin. CONCLUSION: Since a greater utilization of health-care services has a strong positive effect on the current and future health status of women and their children, the health-care authorities in Ghana should make every effort to extend this coverage. In particular, since the results of the first step of the bivariate probit regressions suggest that the educational attainment of women is a strong determinant of enrollment, and those with low education and unable to read are less likely to enroll, information on the NHIS should be disseminated in ways that reach those with little or no education. Moreover, the availability of government health facilities in a region is associated with higher likelihood of enrollment in the NHIS. Accordingly, extending geographical access is an important strategy for expanding NHIS membership and improving access to health-care. PMID- 26864988 TI - Laccase Inhibition by Arsenite/Arsenate: Determination of Inhibition Mechanism and Preliminary Application to a Self-Powered Biosensor. AB - The reversible inhibition of laccase by arsenite (As(3+)) and arsenate (As(5+)) is reported for the first time. Oxygen-reducing laccase bioelectrodes were found to be inhibited by both arsenic species for direct electron-transfer bioelectrodes (using anthracene functionalities for enzymatic orientation) and for mediated electron-transfer bioelectrodes [using 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) as an electron mediator]. Both arsenic species were determined to behave via a mixed inhibition model (behaving closely to that of uncompetitive inhibitors) when evaluated spectrophotometrically using ABTS as the electron donor. Finally, laccase bioelectrodes were employed within an enzymatic fuel cell, yielding a self powered biosensor for arsenite and arsenate. This conceptual self-powered arsenic biosensor demonstrated limits of detection (LODs) of 13 MUM for arsenite and 132 MUM for arsenate. Further, this device possessed sensitivities of 0.91 +/- 0.07 mV/mM for arsenite and 0.98 +/- 0.02 mV/mM for arsenate. PMID- 26864991 TI - The Ethics of Allocating Uterine Transplants. AB - In September 2014, a healthy male child was born in Sweden following a successful uterine transplantation (UTx). The event brought hope to many women without functional uteruses around the world. Having a child with a transplanted uterus is now possible, and as knowledge of the procedure proliferates and interest in UTx grows, it is important to begin thinking about how a scarce supply of uteruses will be allocated. This article represents a first discussion of the range of factors that must be considered in answering the allocation question. The primary issues addressed are (1) the motivation to seek treatment, (2) allocation by age, (3) child-rearing capacity, and (4) the amount of infertility treatment required. A set of eligibility and ranking criteria are presented. These criteria are not exhaustive but are intended to spark discussion about how uteruses can be allocated in a just manner. PMID- 26864989 TI - Cross-resistance to fluconazole induced by exposure to the agricultural azole tetraconazole: an environmental resistance school? AB - This study aimed to investigate the influence of tetraconazole and malathion, both used in agricultural activities, on resistance to fluconazole, itraconazole and voriconazole in Candida parapsilosis ATCC 22019. The susceptibility to tetraconazole, malathion, fluconazole, itraconazole and voriconazole, through broth microdilution. Then, 12 independent replicates, were separated and exposed to four treatment groups, each one containing three replicates: G1: tetraconazole; G2: malathion; G3: fluconazole (positive control); G4: negative control. Replicates from G1, G2 and G3, were exposed to weekly increasing concentrations of tetraconazole, malathion and fluconazole, respectively, ranging from MIC/2 to 32 * MIC, throughout 7 weeks. The exposure to tetraconazole, but not malathion, decreased susceptibility to clinical azoles, especially fluconazole. The tetraconazole-induced fluconazole resistance is partially mediated by the increased activity of ATP-dependent efflux pumps, considering the increase in antifungal susceptibility after the addition of the efflux pump inhibitor, promethazine, and the increase in rhodamine 6G efflux and CDR gene expression in the G1 replicates. Moreover, MDR expression was only detected in G1 and G3 replicates, suggesting that MDR pumps are also involved in tetraconazole induced fluconazole resistance. It is noteworthy that tetraconazole and fluconazole-treated replicates behaved similarly, therefore, resistance to azoles of clinical use may be a consequence of using azoles in farming activities. PMID- 26864990 TI - Cost of Inpatient Care of Patients With Pemphigus in the United States: Translating Dollars and Cents Into Improved Patient Care. PMID- 26864992 TI - A non-destructive n-doping method for graphene with precise control of electronic properties via atomic layer deposition. AB - Graphene applications require high precision control of the Fermi level and carrier concentration via a nondestructive doping method. Here, we develop an effective n-doping technique using atomic layer deposition (ALD) of ZnO thin films on graphene through a reactive molecular layer. This ALD doping method is nondestructive, simple, and precise. The ZnO thin films on graphene are uniform, conformal, of good quality with a low density of pinholes, and finely tunable in thickness with 1 A resolution. We demonstrate graphene transistor control in terms of the Dirac point, carrier density, and doping state as a function of the ZnO thickness. Moreover, ZnO functions as an effective thin-film barrier against air-borne water and oxygen on the graphene, resulting in extraordinary stability in air for graphene devices. ZnO ALD was also applied to other two-dimensional materials including MoS2 and WSe2, which substantially enhanced electron mobility. PMID- 26864993 TI - Experimental investigation of the biomechanics of urethral tissues and structures. AB - NEW FINDINGS: What is the central question of this study? Prostheses for treatment of urinary incontinence elicit complications associated with an inadequate mechanical action. This investigation aimed to define a procedure addressed to urethral mechanical characterization. Experimental tests are the basis for constitutive formulation, with a view to numerical modelling for investigation of the interaction between the tissues and a prosthesis. What is the main finding and its importance? Horse urethra, selected for its histomorphometric similarity to human urethra, was characterized by integrated histological analysis and mechanical tests on the biological tissue and structure, leading to constitutive formulation. A non-linear, anisotropic and time-dependent response was found, representing a valid basis for development of a numerical model to interpret the functional behaviour of the urethra. Urinary dysfunction can lead to incontinence, with an impact on the quality of life. Severe dysfunction can be overcome surgically by the use of an artificial urinary sphincter. Nonetheless, several complications may result from inappropriate functioning of the prosthesis, in many instances resulting from an unsuitable mechanical action of the device on the urethral tissues. Computational models allow investigation of the mechanical interaction between biological tissues and biomedical devices, representing a potential support for surgical practice and prosthesis design. The development of such computational tools requires experimental data on the mechanics of biological tissues and structures, which are rarely reported in the literature. The aim of this study was to provide a procedure for the mechanical characterization of urethral tissues and structures. The experimental protocol included the morphometric and histological analysis of urethral tissues, the mechanical characterization of the response of tissues to tensile and stress-relaxation tests and evaluation of the behaviour of urethral structures by inflation tests. Results from the preliminary experiments were processed, adopting specific model formulations, and also providing the definition of parameters that characterize the elastic and viscous behaviour of the tissues. Different experimental protocols, leading to a comprehensive set of experimental data, allow for a reciprocal assessment of reliability of the investigation approach. PMID- 26864995 TI - Linguistic profiles of children with CI as compared with children with hearing or specific language impairment. AB - BACKGROUND: The spoken language difficulties of children with moderate or severe to profound hearing loss are mainly related to limited auditory speech perception. However, degraded or filtered auditory input as evidenced in children with cochlear implants (CIs) may result in less efficient or slower language processing as well. To provide insight into the underlying nature of the spoken language difficulties in children with CIs, linguistic profiles of children with CIs are compared with those of hard-of-hearing (HoH) children with conventional hearing aids and children with specific language impairment (SLI). AIMS: To examine differences in linguistic abilities and profiles of children with CIs as compared with HoH children and children with SLI, and whether the spoken language difficulties of children with CIs mainly lie in limited auditory perception or in language processing problems. METHODS & PROCEDURE: Differences in linguistic abilities and differential linguistic profiles of 47 children with CI, 66 HoH children with moderate to severe hearing loss, and 127 children with SLI are compared, divided into two age cohorts. Standardized Dutch tests were administered. Factor analyses and cluster analyses were conducted to find homogeneous linguistic profiles of the children. OUTCOMES & RESULTS: The children with CIs were outperformed by their HoH peers and peers with SLI on most linguistic abilities. Concerning the linguistic profiles, the largest group of children with CIs and HoH children shared similar profiles. The profiles observed for most of the children with SLI were different from those of their peers with hearing loss in both age cohorts. CONCLUSIONS & IMPLICATIONS: Results suggest that the underlying nature of spoken language problems in most children with CIs manifests in limited auditory perception instead of language processing difficulties. However, there appears to be a subgroup of children with CIs whose linguistic profiles resemble those of children with SLI. PMID- 26864996 TI - Shared Care Contributions to Self-Care and Quality of Life in Chronic Cardiac Patients. AB - Shared care is an interpersonal interaction system composed of communication, decision making, and reciprocity; it is used by patients and family caregivers (care dyads) to exchange social support. This study's purpose was to describe the contributions of shared care to outcomes for individuals with cardiac disease. A secondary data analysis was used to answer the following questions. What is the association between elements of shared care and patient outcomes? Do dyad perceptions of shared care differentially contribute to patient outcomes? Participants in this study were 93 individuals with a cardiac disease and 93 family caregivers. Composite index structured equation modeling was the analytic tool. Caregiver communication and reciprocity were related to patient mental quality of life. Patient communication and reciprocity were related to their own mental and physical quality of life and self-care confidence. Findings from this study contribute a better understanding of how care dyads are integral to patient outcomes. PMID- 26864994 TI - 'Coz football is what we all have': masculinities, practice, performance and effervescence in a gender-sensitised weight-loss and healthy living programme for men. AB - In this paper we use a social practice approach to explore men's experience of Football Fans in Training (FFIT), a group-based weight management programme for men that harnesses men's symbolic attachment to professional football clubs to engage them in lifestyle change. FFIT is delivered by community coaches in clubs' stadia and is gender-sensitised in relation to context, content and style of delivery. Using a 'toolkit' of concepts from the work of Bourdieu, Goffman and Durkheim we analysed data from 13 focus group discussions with participants, and fieldwork notes from programme observations to investigate the appeal and success of FFIT, and how it worked to support change. Our analysis builds on our work on the importance of shared symbolic commitment to the football club and being with 'men like me' to understand how the interaction context facilitated 'effervescent' experiences. These experiences encouraged men to make changes to their diet and physical activity, talk about them, practice performing them and implement them in their lives. Thus a social practice approach illuminated the social processes through which lifestyle change was achieved, and we argue that it can deepen and enrich both intervention design and evaluation. PMID- 26864997 TI - Psycho-educational programmes led by experienced nurses may improve the coping abilities of implantable cardioverter defibrillator recipients. PMID- 26864998 TI - Glial Cells are Involved in Itch Processing. AB - Recent discoveries in itch neurophysiology include itch-selective neuronal pathways, the clinically relevant non-histaminergic pathway, and elucidation of the notable similarities and differences between itch and pain. Potential involvement of glial cells in itch processing and the possibility of glial modulation of chronic itch have recently been identified, similarly to the established glial modulation of pain processing. This review outlines the similarities and differences between itch and pain, and how different types of central and peripheral glial cells may be differentially involved in the development of chronic itch akin to their more investigated role in chronic pain. Improvements are needed in the management of chronic itch, and future basic and interventional studies on glial activity modulation would both enhance our understanding of mechanisms underlying the chronification of itch and provide novel opportunities for the prevention or treatment of this debilitating and common condition. PMID- 26865000 TI - Histological and transcriptome analyses of testes from Duroc and Meishan boars. AB - Meishan boars are known for their early sexual maturity. However, they exhibit a significantly smaller testicular size and a reduced proportion of Sertoli cells and daily sperm production compared with Duroc boars. The testes of Duroc and Meishan boars at 20, 75 and 270 days of age were used for histological and transcriptome analyses. Haematoxylin-eosin staining was conducted to observe histological structure of the testes in Duroc and Meishan boars at different ages. Although spermatogenesis occurred prior to 75 days in Meishan boars, the number of spermatogonia and Sertoli cells in Meishan boars were less than in Duroc boars at adulthood. The diameters of the seminiferous tubules of the testes differed significantly during the initiation of development of the seminiferous tubules between the two breeds. We obtained differentially expressed functional genes and analysed seven pathways involved in male sexual maturity and spermatogenesis using RNA-seq. We also detected four main alternative splicing events and many single nucleotide polymorphisms from testes. Eight functionally important genes were validated by qPCR, and Neurotrophin 3 was subjected to quantification and cellular localization analysis. Our study provides the first transcriptome evidence for the differences in sexual function development between Meishan and Duroc boars. PMID- 26865002 TI - Does sympathetic overactivation feature all hypertensives? Differences of sympathovagal balance according to night/day blood pressure ratio in patients with essential hypertension. AB - When evaluating the 'night/day BP ratio', both hypertensives and normotensives can be arbitrarily classified into four groups: extreme dippers (ratio ?0.8), dippers (0.8 0.05) was identified as a less significant factor in the context of e-Health in Bangladesh. The findings also revealed that gender was strongly associated with the adoption and use of e-Health services. CONCLUSIONS: The findings of the present study contribute to the development of strategies and policies to enhance e-Health services in Bangladesh. Furthermore, as a result of the generic approach used in this study, the acceptance model developed can be easily modified to investigate the adoption of e-Health in other developing countries. PMID- 26865038 TI - A new approach to road accident rescue. AB - OBJECTIVE: This article develops and validates a new methodology and tool for rescue assistance in traffic accidents, with the aim of improving its efficiency and safety in the evacuation of people, reducing the number of victims in road accidents. METHOD: Different tests supported by professionals and experts have been designed under different circumstances and with different categories of damaged vehicles coming from real accidents and simulated trapped victims in order to calibrate and refine the proposed methodology and tool. RESULTS: To validate this new approach, a tool called App_Rescue has been developed. This tool is based on the use of a computer system that allows an efficient access to the technical information of the vehicle and sanitary information of the common passengers. The time spent during rescue using the standard protocol and the proposed method was compared. CONCLUSION: This rescue assistance system allows us to make vital information accessible in posttrauma care services, improving the effectiveness of interventions by the emergency services, reducing the rescue time and therefore minimizing the consequences involved and the number of victims. This could often mean saving lives. In the different simulated rescue operations, the rescue time has been reduced an average of 14%. PMID- 26865025 TI - Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution. AB - Neuropeptides are evolutionarily ancient mediators of neuronal signalling in nervous systems. With recent advances in genomics/transcriptomics, an increasingly wide range of species has become accessible for molecular analysis. The deuterostomian invertebrates are of particular interest in this regard because they occupy an 'intermediate' position in animal phylogeny, bridging the gap between the well-studied model protostomian invertebrates (e.g. Drosophila melanogaster, Caenorhabditis elegans) and the vertebrates. Here we have identified 40 neuropeptide precursors in the starfish Asterias rubens, a deuterostomian invertebrate from the phylum Echinodermata. Importantly, these include kisspeptin-type and melanin-concentrating hormone-type precursors, which are the first to be discovered in a non-chordate species. Starfish tachykinin type, somatostatin-type, pigment-dispersing factor-type and corticotropin releasing hormone-type precursors are the first to be discovered in the echinoderm/ambulacrarian clade of the animal kingdom. Other precursors identified include vasopressin/oxytocin-type, gonadotropin-releasing hormone-type, thyrotropin-releasing hormone-type, calcitonin-type, cholecystokinin/gastrin type, orexin-type, luqin-type, pedal peptide/orcokinin-type, glycoprotein hormone type, bursicon-type, relaxin-type and insulin-like growth factor-type precursors. This is the most comprehensive identification of neuropeptide precursor proteins in an echinoderm to date, yielding new insights into the evolution of neuropeptide signalling systems. Furthermore, these data provide a basis for experimental analysis of neuropeptide function in the unique context of the decentralized, pentaradial echinoderm bauplan. PMID- 26865039 TI - Effects of Home-Based Tai Chi and Lower Extremity Training and Self-Practice on Falls and Functional Outcomes in Older Fallers from the Emergency Department-A Randomized Controlled Trial. AB - OBJECTIVES: To compare the effects of guided home-based tai chi chuan (TCC) and lower extremity training (LET) and of levels of self-practice on falls and functional outcomes in older fallers. DESIGN: Randomized controlled trial. SETTING: Taipei, Taiwan. PARTICIPANTS: Individuals aged 60 and older who had fall related emergency department visits at least 6 months before participating in the study and ambulated independently at baseline (N = 456). INTERVENTION: Six months of TCC or LET. MEASUREMENTS: Four types of fall measures (falls, time to first fall, fallers, recurrent fallers) and six functional measures (handgrip strength, balance, mobility, fear of falling, depression, cognitive function). RESULTS: The TCC group was significantly less likely than the LET group to experience any falls during the 6-month intervention (incidence rate ratio (IRR) = 0.30, 95% confidence interval (CI) = 0.15-0.60), and the effects remained significant after 12 months of follow-up (IRR = 0.32, 95% CI = 0.14-0.71). These effects remained significant for injurious falls during the 6-month intervention (IRR = 0.33, 95% CI = 0.16-0.68) and the entire 18-month study (IRR = 0.39, 95% CI = 0.18-0.83). Similar results were obtained when another two fall measures (time to first fall, number of fallers) were used. Moreover, participants who independently practiced TCC or LET seven times per week or more were significantly less likely to experience injurious falls during the 6-month intervention (IRR = 0.41, 95% CI = 0.20-0.83) and the 18-month study (IRR = 0.43, 95% CI = 0.21-0.87) than their counterparts, had a significantly longer time to first injurious fall, and were significantly less likely to have an injurious fall during the 6-month intervention. Cognitive function improved to a greater extent in the TCC group than in the LET group over the 18-month study. CONCLUSION: Home-based TCC may reduce the incidence of falls and injurious falls more than conventional LET in older fallers, and the effects may last for at least 1 year. PMID- 26865040 TI - Erratum. PMID- 26865041 TI - Bizarre parosteal osteochondromatous proliferation in the lingual area of the mandibular body versus osteochondroma at the mandibular condyle. AB - BACKGROUND: Bizarre parosteal osteochondromatous proliferation (BPOP) is benign and usually occurs in the small tubular bones of the hands and feet, but it is extremely rare in the oral and maxillofacial region. METHODS: The present study compares a case of BPOP occurring in the lingual area of the right mandibular body with a representative case of osteochondroma occurring in the left mandibular condyle using immunohistochemical methods. RESULTS: BPOP showed no continuity to the cortical bone of the mandible on X-ray and was histologically composed of immature cartilage and bone tissues, whereas osteochondroma showed overgrowth of hypertrophic chondrocytes accompanied by mature bone with endochondral ossification. Although BPOP showed no features of cellular atypia or malignant transformation, it expressed more osteogenic proteins, including BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF, than osteochondroma. Furthermore, the perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP showed stronger immunoreaction of PCNA, p53, beta-catenin, BCL2, pAKT, survivin, 14-3-3, CEA, EMA, pan-K, and S-100 than the tumor cells of osteochondroma. CONCLUSIONS: Therefore, it was presumed that similar to embryonal osteochondroid tissue, BPOP might be activated by osteogenic and oncogenic signaling and that this increased signaling may explain the rapid growth and high recurrence of BPOP. PMID- 26865044 TI - Structures of Trichloromethyl Thiocyanate, CCl3 SCN, in Gaseous and Crystalline State. AB - Trichloromethyl thiocyanate, CCl3 SCN, was structurally studied in both the gas and crystal phases by means of gas electron diffraction (GED) and single-crystal X-ray diffraction (XRD), respectively. Both experimental studies and quantum chemical calculations indicate a staggered orientation of the CCl3 group relative to the SCN group. This conclusion is supported by the similarity of the C-SCN bond length to that of the anti-structure of CH2 ClSCN (Berrueta Martinez et al. Phys. Chem. Chem. Phys. 2015, 17, 15805-15812). Bond lengths and angles are similar for gas and crystal CCl3 SCN structures; however, the crystal structure presents different intermolecular interactions. These include halogen and chalcogen type interactions, the geometry of which was studied. Characteristic C Y???N angles (Y=Cl or S) close to 180 degrees provide evidence for typical sigma hole interactions along the halogen/chalcogen-carbon bond in N???Cl and N???S, intermolecular units. PMID- 26865042 TI - Lack of association between polymorphisms in the CYP1A2 gene and risk of cancer: evidence from meta-analyses. AB - BACKGROUND: Polymorphisms in the CYP1A2 genes have the potential to affect the individual capacity to convert pre-carcinogens into carcinogens. With these comprehensive meta-analyses, we aimed to provide a quantitative assessment of the association between the published genetic association studies on CYP1A2 single nucleotide polymorphisms (SNPs) and the risk of cancer. METHODS: We searched MEDLINE, ISI Web of Science and SCOPUS bibliographic online databases and databases of genome-wide association studies (GWAS). After data extraction, we calculated Odds Ratios (ORs) and 95% confidence intervals (CIs) for the association between the retrieved CYP1A2 SNPs and cancer. Random effect model was used to calculate the pooled ORs. Begg and Egger tests, one-way sensitivity analysis were performed, when appropriate. We conducted stratified analyses by study design, sample size, ethnicity and tumour site. RESULTS: Seventy case control studies and one GWA study detailing on six different SNPs were included. Among the 71 included studies, 42 were population-based case-control studies, 28 hospital-based case-control studies and one genome-wide association study, including total of 47,413 cancer cases and 58,546 controls. The meta-analysis of 62 studies on rs762551, reported an OR of 1.03 (95% CI, 0.96-1.12) for overall cancer (P for heterogeneity < 0.01; I(2) = 50.4%). When stratifying for tumour site, an OR of 0.84 (95% CI, 0.70-1.01; P for heterogeneity = 0.23, I(2) = 28.5%) was reported for bladder cancer for those homozygous mutant of rs762551. An OR of 0.79 (95% CI, 0.65-0.95; P for heterogeneity = 0.09, I(2) = 58.1%) was obtained for the bladder cancer from the hospital-based studies and on Caucasians. CONCLUSIONS: This large meta-analysis suggests no significant effect of the investigated CYP1A2 SNPs on cancer overall risk under various genetic models. However, when stratifying according to the tumour site, our results showed a borderline not significant OR of 0.84 (95% CI, 0.70-1.01) for bladder cancer for those homozygous mutant of rs762551. Due to the limitations of our meta-analyses, the results should be interpreted with attention and need to be further confirmed by high-quality studies, for all the potential CYP1A2 SNPs. PMID- 26865043 TI - Comparison of the influence of ticagrelor and clopidogrel on inflammatory biomarkers and vascular endothelial function for patients with ST-segment elevation myocardial infarction receiving emergency percutaneous coronary intervention: study protocol for a randomized controlled trial. AB - BACKGROUND: The Platelet Inhibition and Patient Outcomes (PLATO, Eur J Prev Cardiol 22(6):734-42, 2015) trial shows that, in patients who have an acute coronary syndrome, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death, but the reason is still uncertain. Both inflammation and vascular endothelian cell dysfunction play important roles in the pathophysiology of atherosclerotic plaques, but whether ticagrelor has superior anti-inflammatory effect and can improve vascular endothelial cell function to a great extent is unknown. METHODS/DESIGN: Patients with STEMI who are scheduled to undergo emergency percutaneous coronary intervention (PCI) will be randomly assigned to receive a loading dose of ticagrelor 180 mg as the treatment group or clopidogrel 600 mg as the control group. After PCI, the treatment group will be treated with ticagrelor 90 mg twice daily while the control group will be treated with clopidogrel 75 mg once daily. The vascular endothelial function will be tested by circulating endothelial cells, and levels of inflammation will be tested by CD40 ligand (CD40L), high sensitivity C reactive protein (hsCRP) and P-selectin. The estimated enrollment sample size will be 350 patients, including 175 in the treatment group and 175 in the control group. DISCUSSION: This study will compare the influence of ticagrelor and clopidogrel on inflammatory biomarkers and vascular endothelial function firstly for STEMI patients receiving emergency PCI and will provide evidence to identify whether ticagrelor inhibits inflammation and improves vascular endothelial cell function to a greater extent than clopidogrel or not. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov (identifier: NCT02123004) on 20 April 2014. PMID- 26865045 TI - Crystal structure and functional implications of the tandem-type universal stress protein UspE from Escherichia coli. AB - BACKGROUND: The universal stress proteins (USP) family member UspE is a tandem type USP that consists of two Usp domains. The UspE expression levels of the Escherichia coli (E. coli) become elevated in response to oxidative stress and DNA damaging agents, including exposure to mitomycin C, cadmium, and hydrogen peroxide. It has been shown that UspA family members are survival factors during cellular growth arrest. The structures and functions of the UspA family members control the growth of E. coli in animal hosts. While several UspA family members have known structures, the structure of E. coli UspE remains to be elucidated. RESULTS: To understand the biochemical function of UspE, we have determined the crystal structure of E. coli UspE at 3.2 A resolution. The asymmetric unit contains two protomers related by a non-crystallographic symmetry, and each protomer contains two tandem Usp domains. The crystal structure shows that UspE is folded into a fan-shaped structure similar to that of the tandem-type Usp protein PMI1202 from Proteus mirabilis, and it has a hydrophobic cavity that binds its ligand. Structural analysis revealed that E. coli UspE has two metal ion binding sites, and isothermal titration calorimetry suggested the presence of two Cd(2+) binding sites with a Kd value of 38.3-242.7 MUM. Structural analysis suggested that E. coli UspE has two Cd(2+) binding sites (Site I: His117, His 119; Site II: His193, His244). CONCLUSION: The results show that the UspE structure has a hydrophobic pocket. This pocket is strongly bound to an unidentified ligand. Combined with a previous study, the ligand is probably related to an intermediate in lipid A biosynthesis. Subsequently, sequence analysis found that UspE has an ATP binding motif (Gly(269)- X2-Gly(272)-X9 Gly(282)-Asn) in its C-terminal domain, which was confirmed by in vitro ATPase activity monitored using Kinase-Glo(r) Luminescent Kinase Assay. However, the residues constituting this motif were disordered in the crystal structure, reflecting their intrinsic flexibility. ITC experiments revealed that the UspE probably has two Cd(2+) binding sites. The His117, His 119, His193, and His244 residues within the beta-barrel domain are necessary for Cd(2+) binding to UspE protein. As mentioned above, USPs are associated with several functions, such as cadmium binding, ATPase function, and involvement in lipid A biosynthesis by some unknown way. PMID- 26865046 TI - Circulating memory T follicular helper subsets, Tfh2 and Tfh17, participate in the pathogenesis of Guillain-Barre syndrome. AB - Circulating memory T follicular helper subsets, Tfh2 and Tfh17 are found to be aberrantly regulated in many autoimmune diseases. However, their roles in the pathogenesis of GBS are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of Tfh2 and Tfh17 in 36 GBS patients (including 24 AMAN and 12 AIDP patients). We found that the absolute counts of total memory Tfh cells were significantly increased in AMAN, while no significant difference in AIDP compared with HC. Furthermore, the levels of the three subsets of memory Tfh cells, Tfh1, Tfh2 and Tfh17, were differentially altered in AMAN. The absolute counts of Tfh1, Tfh2 and Tfh17 were all increased to a higher level in AMAN. The ratio of (Tfh2+Tfh17)/Tfh1 and the percentages of ICOS(+) cells in Tfh2 and Tfh17 cells were greater in AMAN when compared to AIDP and HC, and the former had a positive correlation with the severity of both AMAN and AIDP. Conversely, the percentages of PD1(+) cells in Tfh2 and Tfh17 cells were lower in AMAN than in HC. Therefore, circulating memory Tfh2 and Tfh17 cells might promote the autoantibody-related immune response and serve as useful markers to evaluate the progression of AMAN. PMID- 26865048 TI - The herpes zoster subunit vaccine. AB - INTRODUCTION: Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN). AREAS COVERED: HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age related or other causes of decreased T cell immunity. A concentrated live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 5-8 years. The new HZ subunit (HZ/su or Shingrix) vaccine combines a key surface VZV glycoprotein (E) with T cell boosting adjuvant (AS01B). It is highly efficacious in protection (97%) against HZ in immunocompetent subjects, with no decline in advancing age and protection maintained for >3 years. Phase I-II trials showed safety and similar immunogenicity in severely immunocompromised patients. Local injection site pain and swelling can be severe in a minority (9.5%) but is transient (2 days). EXPERT OPINION: The HZ/su vaccine appears very promising in immunocompetent patients in the ZoE-50 controlled trial. The unblinding of the current ZoE-50 trial and publication of results from the accompanying ZoE-70 trial will reveal more about its mechanism of action and its efficacy against PHN, particularly in subjects >70 years. Phase III trial results in immunocompromised patients are eagerly awaited. PMID- 26865047 TI - Association of adiponectin gene polymorphisms and additional gene-gene interaction with nonalcoholic fatty liver disease in the Chinese Han population. AB - PURPOSE: To investigate the association between the single nucleotide polymorphisms (SNPs) of the adiponectin gene and nonalcoholic fatty liver disease (NAFLD) as well as the impact of the interaction of multiple SNPs on NAFLD risk, based on a Chinese population study. METHODS: A total of 612 subjects (411 male, 201 female) were selected, including 302 NAFLD patients and 310 controls. Three SNPs were selected for genotyping in the case-control study: rs266729, rs822393, and rs1501299. A logistic regression model was used to examine the interaction between the SNPs and NAFLD. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction among SNPs. RESULTS: Logistic analysis showed a significant association between genotypes of variants in rs266729 and rs822393 and increased NAFLD risk. The carriers of the homozygous mutant of two SNP polymorphisms revealed increased NAFLD risk compared to those with wild-type homozygotes; ORs (95 % CI) were 1.31 (1.14-1.81) (p = 0.001) and 1.18 (1.05-1.71) (p = 0.005), respectively. There was a significant two-locus model (p = 0.0010) involving rs266729 and rs822393, indicating a potential gene-gene interaction between rs266729 and rs822393. Overall, the two-locus models had a cross validation consistency of 10 and testing accuracy of 62.17 %. Subjects with the CG or GG and CT or TT genotype have the highest NAFLD risk compared to subjects with the CC-CC genotype; the OR (95 % CI) was 2.52 (1.31-3.82), p < 0.001, after covariate adjustment. CONCLUSIONS: Our results support an important association of the rs266729 (-11377 G/C) and rs822393 (-4522 C/T) polymorphism with increased risk of NAFLD. The interaction analysis showed a combined effect of rs266729 and rs822393 on NAFLD. PMID- 26865049 TI - Mycobacterium phlei cell wall-nucleic acid complex in the treatment of nonmuscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin. AB - INTRODUCTION: Current guidelines recommend cystectomy in patients with high risk NMIBC who fail to respond to BCG. However due to the significant morbidity and mortality of the procedure, many are not candidates or refuse it. No new treatments for this indication have been approved by the US FDA since 1998. AREAS COVERED: A cell wall-nucleic acid complex (MCNA) from M. phlei has been investigated for possible application in patients with BCG refractory NMIBC. The development of this biological from the original studies is reviewed, together with the clinical trials leading to a submission to the FDA. Its efficacy and safety are presented together with comparative analysis of alternative treatments, most of which are used off-label. In addition, new combinations of standard therapies are described as well as single agents exhibiting activity against these tumors. EXPERT OPINION: MCNA has shown activity against high risk BCG refractory bladder cancer and offers an alternative to current treatments. The clinical experience remains limited and the optimal therapeutic regimen (dose, frequency) have not been firmly established. Patients and clinicians would welcome the introduction of a compound that may delay or prevent the risks and negative impact in quality of life of cystectomy and urinary diversion. PMID- 26865050 TI - Composition and dynamics of the respiratory tract microbiome in intubated patients. AB - BACKGROUND: Lower respiratory tract infection (LRTI) is a major contributor to respiratory failure requiring intubation and mechanical ventilation. LRTI also occurs during mechanical ventilation, increasing the morbidity and mortality of intubated patients. We sought to understand the dynamics of respiratory tract microbiota following intubation and the relationship between microbial community structure and infection. RESULTS: We enrolled a cohort of 15 subjects with respiratory failure requiring intubation and mechanical ventilation from the medical intensive care unit at an academic medical center. Oropharyngeal (OP) and deep endotracheal (ET) secretions were sampled within 24 h of intubation and every 48-72 h thereafter. Bacterial community profiling was carried out by purifying DNA, PCR amplification of 16S ribosomal RNA (rRNA) gene sequences, deep sequencing, and bioinformatic community analysis. We compared enrolled subjects to a cohort of healthy subjects who had lower respiratory tract sampling by bronchoscopy. In contrast to the diverse upper respiratory tract and lower respiratory tract microbiota found in healthy controls, critically ill subjects had lower initial diversity at both sites. Diversity further diminished over time on the ventilator. In several subjects, the bacterial community was dominated by a single taxon over multiple time points. The clinical diagnosis of LRTI ascertained by chart review correlated with low community diversity and dominance of a single taxon. Dominant taxa matched clinical bacterial cultures where cultures were obtained and positive. In several cases, dominant taxa included bacteria not detected by culture, including Ureaplasma parvum and Enterococcus faecalis. CONCLUSIONS: Longitudinal analysis of respiratory tract microbiota in critically ill patients provides insight into the pathogenesis and diagnosis of LRTI. 16S rRNA gene sequencing of endotracheal aspirate samples holds promise for expanded pathogen identification. PMID- 26865053 TI - Erratum to: Potential of carbon nanotubes in algal biotechnology. PMID- 26865051 TI - Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells. AB - The cellular physiology and biology of human cardiac c-kit(+) progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c-kit(+) progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c-kit(+) cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca(2+) (Ca(2+) i ), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4alpha-phorbol 12-13-dicaprinate induced Ca(2+) i oscillations, which can be inhibited by the TRPV4 blocker RN-1734. The alteration of Ca(2+) i by probenecid or 4alpha-phorbol 12-13-dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c-kit(+) progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells. PMID- 26865054 TI - Deformation and internal stress in a red blood cell as it is driven through a slit by an incoming flow. AB - To understand the deformation and internal stress of a red blood cell when it is pushed through a slit by an incoming flow, we conduct a numerical investigation by combining a fluid-cell interaction model based on boundary-integral equations with a multiscale structural model of the cell membrane that takes into account the detailed molecular architecture of this biological system. Our results confirm the existence of cell 'infolding', during which part of the membrane is inwardly bent to form a concave region. The time histories and distributions of area deformation, shear deformation, and contact pressure during and after the translocation are examined. Most interestingly, it is found that in the recovery phase after the translocation significant dissociation pressure may develop between the cytoskeleton and the lipid bilayer. The magnitude of this pressure is closely related to the locations of the dimple elements during the transit. Large dissociation pressure in certain cases suggests the possibility of mechanically induced structural remodeling and structural damage such as vesiculation. With quantitative knowledge about the stability of intra-protein, inter-protein and protein-to-lipid linkages under dynamic loads, it will be possible to achieve numerical prediction of these processes. PMID- 26865052 TI - ITF2357 transactivates Id3 and regulate TGFbeta/BMP7 signaling pathways to attenuate corneal fibrosis. AB - Corneal fibrosis is often seen in patients with ocular trauma and infection that compromises corneal transparency resulting in vision loss. Treatment strategies including NSAIDs, steroids, MMC and corneal transplants have shown tremendous success but with several side effects and cellular toxicity. Histone deacetylase inhibitors (HDACi) have been shown to inhibit corneal fibrosis via TGFbeta signaling pathway. In this study, we investigated safety, efficacy and mechanism of action of a HDACi, ITF2357 in TGFbeta-stimulated in vitro primary human cornea stromal fibroblasts (pHCSFs) and in vivo in a photorefractive keratectomy-treated rabbit model of corneal fibrosis. We found that in vivo ITF2357 decreased collagen I, collagen IV, fibronectin, integrin alphaVbeta3 expression with a reduction in corneal haze. In addition, ITF2357 reduced myofibroblast formation, suppressed phosphorylation of Smad proteins in TGFbeta pathway and inhibited key responsive protein, P4HA1 involved in pro-collagen synthesis. Treatment of pHCSFs with ITF2357 activated BMP7 levels and expressed all the members of inhibitor of differentiation proteins (Id1-Id4), however, it failed to rescue TGFbeta-driven transdifferentiation of fibroblasts to myofibroblasts in the presence of siRNA specific to Id3. We conclude that ITF2357 is a potential anti-fibrotic drug that exerts its action via activation of Id3, a downstream target of TGFbeta/BMP7 signaling pathways. PMID- 26865055 TI - Resection of colorectal liver metastases in the elderly-Is it justified? AB - BACKGROUND AND OBJECTIVES: Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations. METHODS: Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 +/- 4 and 56.5 +/- 9 years). Patient and tumor characteristics, perioperative, and long term outcomes were compared. RESULTS: Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 +/- 109 versus 261 +/- 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P < 0.0001). One elderly patient died following surgery (1.8%). Length of hospital stay was similar between groups. No difference in 3-year survival was demonstrated. CONCLUSIONS: Although associated with a small increase in postoperative morbidity and mortality, liver resection may be performed safely and effectively in carefully selected elderly patients. J. Surg. Oncol. 2016;113:485-488. (c) 2016 Wiley Periodicals, Inc. PMID- 26865056 TI - Organ-specific antibodies in LADA patients for the prediction of insulin dependence. AB - AIM OF THE STUDY: The aim of the present study was to define the frequency of organ-specific and non-organ-specific autoantibodies in a cohort of Latent Autoimmune Diabetes in Adults (LADA) patients and to test whether multiple antibodies positivity could be a predictor of early insulin dependence. MATERIALS AND METHODS: We enrolled 210 LADA and 210 type 2 diabetes mellitus (T2D) patients. In all subjects anti-islet antigen-2 (IA-2Ab), anti-thyroperoxidase (TPOAb), anti-zinc transporter 8 (ZnT8Ab), anti-nuclear (ANA), anti-parietal cell (APCA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), and anti-reticulin (ARA) circulating antibodies were assessed. RESULTS: The frequency of TPOAb, ZnT8Ab, APCA, and IA-2Ab positivity was, respectively, detected in 40.0%, 32.4%, 24.7%, and 9.5% of LADA patients, whereas their frequency was significantly lower in T2D patients (11.4%, 1.9%, 9.5%, and 0.0%, respectively, p < 0.001). The frequency of ANA was the same in both groups whereas the frequency of ASMA, ARA, AMA, and LKM was very low (range 0.0-3.3%). The presence of TPOAb associated with ZnT8Ab, IA-2Ab, or APCA allows one to predict the progression of disease with a high specificity but low sensibility. CONCLUSIONS: LADA patients show an increased frequency of organ- and non-organ specific antibodies. Consequently, a screening is worthwhile in these patients. The simultaneous presence of TPOAb with ZnT8, IA-2Ab, or APCA may help differentiate clinical phenotypes and predict faster insulin dependence in LADA patients. PMID- 26865058 TI - Copper-catalyzed oxidative carbon-heteroatom bond formation: a recent update. AB - This review updates recent advances in Cu-catalyzed (anaerobic) oxidative carbon heteroatom bond formation on sp(3)- and sp(2)-C-H bonds as well as alkenes, classified according to the types of stoichiometric oxidants. PMID- 26865057 TI - Combined use of nitrification inhibitor and struvite crystallization to reduce the NH3 and N2O emissions during composting. AB - Struvite crystallization (SCP) is combined with a nitrification inhibitor (dicyandiamide, DCD) to mitigate the NH3 and N2O emission during composting. The MgO and H3PO4 were added at a rate of 15% (mole/mole) of initial nitrogen, and the DCD was added at rates of 0%, 2.5%, 5.0%, 7.5% and 10% (w/w) of initial nitrogen respectively. Results showed that the combination use of SCP and DCD was phytotoxin free. The SCP could significantly reduce NH3 losses by 45-53%, but not the DCD. The DCD significantly inhibits nitrification when the content was higher than 50mgkg(-1), and that could reduce the N2O emission by 76.1-77.6%. The DCD degraded fast during the thermophilic phase, as the nitrification will be inhibited by the high temperature and high free ammonia content in this stage, the DCD was suggested to be applied in the maturing periods by 2.5% of initial nitrogen. PMID- 26865059 TI - Amyloid properties of the leader peptide of variant B cystatin C: implications for Alzheimer and macular degeneration. AB - Variant B (VB) of cystatin C has a mutation in its signal peptide (A25T), which interferes with its processing leading to reduced secretion and partial retention in the vicinity of the mitochondria. There are genetic evidences of the association of VB with Alzheimer's disease (AD) and age-related macular degeneration (AMD). Here, we investigated aggregation and amyloid propensities of unprocessed VB combining computational and in vitro studies. Aggregation predictors revealed the presence of four aggregation-prone regions, with a strong one at the level of the signal peptide, which indeed formed toxic aggregates and mature amyloid fibrils in solution. In light of these results, we propose for the first time the role of the signal peptide in pathogenesis of AD and AMD. PMID- 26865061 TI - Qualitative research and The BMJ. PMID- 26865060 TI - The Antiaging Gene Klotho Regulates Proliferation and Differentiation of Adipose Derived Stem Cells. AB - Klotho was originally discovered as an aging-suppressor gene. The purpose of this study was to investigate whether secreted Klotho (SKL) affects the proliferation and differentiation of adipose-derived stem cells (ADSCs). RT-PCR and Western blot analysis showed that short-form Klotho was expressed in mouse ADSCs. The Klotho gene mutation KL(-/-) significantly decreased proliferation of ADSCs and expression of pluripotent transcription factors (Nanog, Sox-2, and Oct-4) in mice. The adipogenic differentiation of ADSCs was also decreased in KL(-/-) mice. Incubation with Klotho-deficient medium decreased ADSC proliferation, pluripotent transcription factor levels, and adipogenic differentiation, which is similar to what was found in KL(-/-) mice. These results indicate that Klotho deficiency suppresses ADSC proliferation and differentiation. Interestingly, treatment with recombinant SKL protein rescued the Klotho deficiency-induced impairment in ADSC proliferation and adipogenic differentiation. SKL also regulated ADSCs' differentiation to other cell lineages (osteoblasts, myofibroblasts), indicating that SKL maintains stemness of ADSCs. It is intriguing that overexpression of SKL significantly increased PPAR-gamma expression and lipid formation in ADSCs following adipogenic induction, indicating enhanced adipogenic differentiation. Overexpression of SKL inhibited expression of TGFbeta1 and its downstream signaling mediator Smad2/3. This study demonstrates, for the first time, that SKL is essential to the maintenance of normal proliferation and differentiation in ADSCs. Klotho regulates adipogenic differentiation in ADSCs, likely via inhibition of TGFbeta1 and activation of PPAR-gamma. Stem Cells 2016;34:1615 1625. PMID- 26865064 TI - Increased nuchal translucency and pregnancy outcome: a retrospective study of 1063 consecutive singleton pregnancies in a single referral institution. PMID- 26865063 TI - Comment on "Ventricular non-compaction cardiomyopathy: prenatal diagnosis and pathology". PMID- 26865062 TI - Strain-transcending immune response generated by chimeras of the malaria vaccine candidate merozoite surface protein 2. AB - MSP2 is an intrinsically disordered protein that is abundant on the merozoite surface and essential to the parasite Plasmodium falciparum. Naturally-acquired antibody responses to MSP2 are biased towards dimorphic sequences within the central variable region of MSP2 and have been linked to naturally-acquired protection from malaria. In a phase IIb study, an MSP2-containing vaccine induced an immune response that reduced parasitemias in a strain-specific manner. A subsequent phase I study of a vaccine that contained both dimorphic forms of MSP2 induced antibodies that exhibited functional activity in vitro. We have assessed the contribution of the conserved and variable regions of MSP2 to the generation of a strain-transcending antibody response by generating MSP2 chimeras that included conserved and variable regions of the 3D7 and FC27 alleles. Robust anti MSP2 antibody responses targeting both conserved and variable regions were generated in mice, although the fine specificity and the balance of responses to these regions differed amongst the constructs tested. We observed significant differences in antibody subclass distribution in the responses to these chimeras. Our results suggest that chimeric MSP2 antigens can elicit a broad immune response suitable for protection against different strains of P. falciparum. PMID- 26865066 TI - Progression of gray matter atrophy in seizure-free patients with temporal lobe epilepsy. AB - OBJECTIVES: To investigate the presence and progression of gray matter (GM) reduction in seizure-free patients with temporal lobe epilepsy (TLE). METHODS: We enrolled 39 consecutive TLE patients, seizure-free for at least 2 years--20 with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 19 with normal MRI (TLE-NL), and 74 healthy controls. For longitudinal analysis, we included individuals who had a second MRI with minimum interval of 18 months: 21 patients (10 TLE-HS, 11 TLE-NL) and 11 controls. Three-dimensional (3D) T1 weighted images acquired in 3 Tesla MRI were analyzed with voxel-based morphometry (VBM). The images of patients with right-sided interictal epileptogenic zone (EZ) were right-left flipped, as well as a comparable proportion of controls. Cross-sectional analysis: The patients' images from each group were compared to controls to investigate differences in GM volumes. Longitudinal analysis: The first and second images were compared in each group to look for decreased GM volume. RESULTS: Cross-sectional analysis: Patients with TLE-HS had diffuse GM atrophy, including hippocampus and parahippocampal gyrus, insula, frontal, and occipital lobes ipsilateral to EZ, bilateral thalamus and contralateral orbitofrontal gyrus, and caudate. In contrast, TLE-NL group did not present significant differences compared to controls. Longitudinal analysis: TLE HS presented progressive GM reduction in ipsilateral insula and occipital lobe, contralateral motor area, and bilateral temporal and frontal lobes. TLE-NL had GM progression in ipsilateral hypothalamus and parietal lobe, contralateral cerebellum, and bilateral temporal lobe. Controls did not show changes in GM volume between MRIs. SIGNIFICANCE: Diffuse extrahippocampal GM atrophy is present in seizure-free patients with TLE-HS. In addition, there is progressive GM atrophy in patients with and without HS. These results demonstrate that not only ongoing seizures are involved in the progression of GM atrophy. An underlying pathologic mechanism could be responsible for progressive brain volume loss in TLE patients even in seizure-free periods. PMID- 26865065 TI - Associations of sex steroid hormones with mortality in women with breast cancer. AB - Epidemiological studies have demonstrated associations between circulating levels of sex steroid hormones and risk of breast cancer in postmenopausal women. However, data on associations with breast cancer survival are limited. We measured levels of estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG), in serum collected on average 30 months after diagnosis from 358 postmenopausal women diagnosed with stage I-IIIA breast cancer between 1995 and 1998 who participated in a multiethnic, prospective cohort study. Women were followed through December, 2012. We evaluated associations between log transformed analytes and breast cancer-specific and all-cause mortality fitting multivariable Cox proportional hazards models. Over a median of 14.5 years of follow-up, 102 deaths occurred; 43 of these were due to breast cancer. In models adjusted for ethnicity/study site, age, body mass index, and tumor stage, increased levels of log-transformed SHBG were associated with reduced risk of both breast cancer-specific mortality (hazard ratio, HR 0.48; 95 % confidence interval, CI 0.26-0.89) and all-cause mortality (HR 0.64, 95 % CI 0.43-0.97). There were no associations between levels of estradiol, estrone, or testosterone for either endpoint. In subgroup analyses, after correction for multiple testing, increased estrone was significantly associated with reduced risk for breast cancer-specific mortality among participants with ER-negative tumors (HR 0.16, 95 % CI 0.05-0.63) but not among participants with ER-positive tumors. Increased serum levels of SHBG were associated with decreased risk of breast cancer specific and all-cause mortality in women with breast cancer. These results should be confirmed in larger breast cancer survivor cohorts. PMID- 26865068 TI - Unusual Case of Left Bronchial Compression by Aneurysmal Pulmonary Arteries in a Child With Atrial Septal Defect. AB - We report an uncommon case of large ostium secundum atrial septal defect (ASD) with severe pulmonary arterial hypertension, with associated aneurysmal dilatation of the pulmonary arteries (PAs) leading to compression of the left main bronchus and collapse of the entire left lung in a 15-month-old female child. The patient was managed by surgical closure of the ASD, translocation of the right PA anterior to the aorta with PA aneurysmorrhaphy. Left bronchial compression was relieved with complete lung expansion on the third postoperative day. PMID- 26865067 TI - Integration of Hybrid and Single Ventricle Rehabilitation Techniques to Treat a Neonate After Iatrogenic Mitral Injury. AB - Neonatal critical aortic stenosis is life threatening and requires intervention shortly after birth. Early percutaneous aortic valvuloplasty is generally considered to be an effective way to obtain reliable prograde flow. We describe the integrated use of hybrid, open surgical, and single ventricle rehabilitation techniques to successfully treat a neonate with borderline left-sided cardiac structures, who sustained a complication from balloon aortic valvuloplasty. PMID- 26865069 TI - Totally Anomalous Pulmonary Venous Connection With Obliterated Vertical Vein. AB - A rare variant of totally anomalous pulmonary venous connection with obliterated infradiaphragmatic vertical vein is described. A 20-day-old male child weighing 2.2 kg was admitted with cyanosis and tachypnea. Pulmonary venous return was found to be entirely through a tortuous pulmonary-to-systemic venous collateral channel, as the descending vertical vein ended blindly. PMID- 26865070 TI - Contrasting Patterns of Evolutionary Diversification in the Olfactory Repertoires of Reptile and Bird Genomes. AB - Olfactory receptors (ORs) are membrane proteins that mediate the detection of odorants in the environment, and are the largest vertebrate gene family. Comparative studies of mammalian genomes indicate that OR repertoires vary widely, even between closely related lineages, as a consequence of frequent OR gains and losses. Several studies also suggest that mammalian OR repertoires are influenced by life history traits. Sauropsida is a diverse group of vertebrates group that is the sister group to mammals, and includes birds, testudines, squamates, and crocodilians, and represents a natural system to explore predictions derived from mammalian studies. In this study, we analyzed olfactory receptor (OR) repertoire variation among several representative species and found that the number of intact OR genes in sauropsid genomes analyzed ranged over an order of magnitude, from 108 in the green anole to over 1,000 in turtles. Our results suggest that different sauropsid lineages have highly divergent OR repertoire composition that derive from lineage-specific combinations of gene expansions, losses, and retentions of ancestral OR genes. These differences also suggest that varying degrees of adaption related to life history have shaped the unique OR repertoires observed across sauropsid lineages. PMID- 26865072 TI - A low rate of multiple maternity for pregnant male northern pipefish Syngnathus fuscus. AB - Microsatellite parentage analysis was applied to 22 broods of the northern pipefish Syngnathus fuscus for the first time. The majority of males mated singly, 23% of males mated with two females, and no males mated with more than two females. The arrangement of embryos within the brood pouch of multiply mated males reflects a previously undocumented fill pattern where full-sib groups are segregated within the pouch by both right and left sides as well as anterior and posterior ends. PMID- 26865073 TI - Molecular Epidemiological Characterization and Health Burden of Thalassemias in the Chaoshan Region, People's Republic of China. AB - Thalassemia is one of the most prevalent inherited disease in southern China. However, there have been only a few epidemiological studies of thalassemia in the Chaoshan region of Guangdong Province, People's Republic of China (PRC). A total of 6231 unrelated subjects in two main geographical cities of the Chaoshan region was analyzed for thalassemia. Seven hundred and thirty-six cases of suspected thalassemia carriers with microcytosis [mean corpuscular volume (MCV) <82.0 fL] were found by complete blood cell (CBC) count, and were tested by reverse dot blot gene chip to reveal a total of 331 mutant chromosomes, including 278 alpha thalassemia (alpha-thal) alleles and 53 beta-thalassemia (beta-thal) alleles. The most common alpha-thal mutations were the Southeast Asian (- -(SEA)), followed by the -alpha(3.7) (rightward) and -alpha(4.2) (leftward) deletions. The two most common beta-thal mutations were HBB: c.316-197C>T and HBB: c.126_129delCTTT, accounting for 69.81% of the beta-thal defects in the studied individuals. In addition, a rare mutation, Cap +1 (A>C) (HBB: c.-50A>C) was described for the first time in the Chaoshan region. Our results gave a heterozygote frequency of 5.31% for common alpha- and beta-thal in the Chaoshan region, and also indicated a higher prevalence of thalassemia with a heterozygote frequency of 6.29% in Chaozhou, followed by Shantou (3.37%). This study provided a detailed prevalence and molecular characterization of thalassemia in the Chaoshan region, and will be valuable for developing a strategy for prevention of thalassemia and reducing excessive health care costs in this area. PMID- 26865071 TI - Conservation, Duplication, and Divergence of Five Opsin Genes in Insect Evolution. AB - Opsin proteins covalently bind to small molecular chromophores and each protein chromophore complex is sensitive to particular wavelengths of light. Multiple opsins with different wavelength absorbance peaks are required for color vision. Comparing opsin responses is challenging at low light levels, explaining why color vision is often lost in nocturnal species. Here, we investigated opsin evolution in 27 phylogenetically diverse insect species including several transitions between photic niches (nocturnal, diurnal, and crepuscular). We find widespread conservation of five distinct opsin genes, more than commonly considered. These comprise one c-opsin plus four r-opsins (long wavelength sensitive or LWS, blue sensitive, ultra violet [UV] sensitive and the often overlooked Rh7 gene). Several recent opsin gene duplications are also detected. The diversity of opsin genes is consistent with color vision in diurnal, crepuscular, and nocturnal insects. Tests for positive selection in relation to photic niche reveal evidence for adaptive evolution in UV-sensitive opsins in day flying insects in general, and in LWS opsins of day-flying Lepidoptera specifically. PMID- 26865074 TI - C-reactive protein increases with gestational age during pregnancy among Chinese women. AB - OBJECTIVE: To examine the concentration of C-reactive protein (CRP) in relation to gestational weeks during pregnancy among Chinese women. METHODS: From a randomized control trial of prenatal supplementation with folic acid, iron-folic acid, and multiple micronutrients in China, we examined 834 pregnant women with CRP measured initially between 5 and 20 weeks and at follow-up between 28 and 32 weeks gestation. We calculated and plotted CRP geometric means by gestational weeks. The same analysis was repeated for women who had normal pregnancies (624 women) by excluding women with stillbirth, preterm, small for gestational age, body mass index <18.5 kg/m(2) or >30 kg/m(2) at enrollment, and hypertension or anemia during pregnancy. RESULTS: We observed a significant positive trend between log-transformed CRP and gestational age from 5 to 20 weeks and from 28 to 32 weeks both in the full sample and in the subset of women who had normal pregnancies. CRP geometric mean was 0.81 mg/l at 5-7 weeks of gestation, 2.85 mg/l at 19-20 weeks of gestation, and 3.89 mg/l at 32 weeks of gestation. A similar increasing trend in the CRP median or percentage of elevated CRP were also observed. CONCLUSION: We concluded that CRP increased with gestational age among healthy Chinese women who delivered healthy infants. Am. J. Hum. Biol. 28:574-579, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26865075 TI - Reconstruction of body height from the skeleton: Testing a dozen different methods for consistency of their results. AB - SUMMARY: There are a number of methods of physical anthropology available to reconstruct living stature from skeletal remains. Some methods use dimensions of just a few bones, together with regression equations (mathematical, see Table 1: 1-7), while other methods require the whole skeleton and simply add the heights of specific skeletal components (anatomical, see Table 1: 8-11). This study investigates the consistency that mathematical and anatomical methods can provide in the determination of stature from skeletal remains. A significant difference was found between average heights of the same 20 individuals determined from seven mathematical and four anatomical methods (paired t-test, p < 0.001, df = 19). Mathematical methods provided taller height estimates than anatomical methods; the average difference was 47 mm. A repeated measures ANOVA indicated significant differences in the heights determined by all methods (p < 0.0001). Analysis of variance indicated significant differences in the heights determined by various mathematical methods (p < 0.03), whereas there were no significant differences in the heights amongst various anatomical methods (p < 0.77). When simple proportions of the length of the long bones to stature are used for reconstruction (see Table 1: 12), a bias is shown by mathematical methods to overestimate statures of short individuals and underestimate statures of taller individuals. To reduce this bias of linear regressions, we suggest that alternate methods, such as reduced major axis or organic correlation, should be employed (see Table 1: 13-15). PMID- 26865076 TI - Modeling the isothermal inactivation curves of Listeria innocua CECT 910 in a vegetable beverage under low-temperature treatments and different pH levels. AB - Thermal inactivation kinetics of Listeria innocua CECT 910 inoculated in a vegetable beverage at three pH conditions (4.25, 4.75, and 5.20), four levels of temperature (50, 55, 60, 65C), and different treatment times (0-75 min) were obtained. Survival curves did not follow a log-linear relationship and consequently were fitted to various mathematical models: Weibull, Geeraerd, Cerf with shoulder, and the modified Gompertz equation. Results indicated that the best model for the treatment conditions was the modified Gompertz equation, which provides the best goodness-of-fit and the lowest Akaike information criterion value. Sensitivity analysis indicated that the most influential factors affecting the final microbial load were temperature and time in the case of the higher temperature level (65C) and time in the case of the lower temperature level (50C). PMID- 26865077 TI - Physicochemical, sensory, and nutritional quality of fresh-cut "Rojo Brillante" persimmon affected by maturity stage and antibrowning agents. AB - To prevent enzymatic browning of fresh-cut 'Rojo Brillante' persimmon, different combinations of ascorbic acid (AA) and citric acid (CA) with calcium chloride (CaCl2) were tested in fruit harvested at two maturity stages (MS1 and MS2). Color, firmness, sensory quality, total vitamin C, radical scavenging activity, total phenolic content, and carotenoids were evaluated over nine days of storage at 5 C. Antibrowning dips reduced enzymatic browning if compared with the control samples. Selecting fruits with good firmness and the addition of 10 g/l CaCl2 help prevent loss of firmness of fresh-cut "Rojo Brillante" persimmons treated with acidic solutions as antibrowning agents to control enzymatic browning. The limit of marketability of the persimmon fruit processed at MS1 was significantly reduced by the burst of the disorder known as "flesh browning," and only the samples treated with 10 g/l CA + 10 g/l CaCl2 maintained a limit of marketability close to seven days. At MS2, all the antibrowning solutions allowed a limit of marketability of seven storage days at 5 C. Nutritional quality was not affected by either antibrowning dips or cutting processes, but MS at harvest was. PMID- 26865078 TI - A Thermo- and Mechanoresponsive Cyano-Substituted Oligo(p-phenylene vinylene) Derivative with Five Emissive States. AB - Multiresponsive materials that display predefined photoluminescence color changes upon exposure to different stimuli are attractive candidates for advanced sensing schemes. Herein, we report a cyano-substituted oligo(p-phenylene vinylene) (cyano OPV) derivative that forms five different solvent-free solid-state molecular assemblies, luminescence properties of which change upon thermal and mechanical stimulation. Single-crystal X-ray structural analysis suggested that tolyl groups introduced at the termini of solubilizing side-chains of the cyano-OPV play a pivotal role in its solid-state arrangement. Viewed more broadly, this report shows that the introduction of competing intermolecular interactions into excimer forming chromophores is a promising design strategy for multicolored thermo- and mechanoresponsive luminescent materials. PMID- 26865079 TI - Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. AB - BACKGROUND: Recent studies have revealed that the blood of healthy humans is not as sterile as previously supposed. The objective of this study was to provide a comprehensive description of the microbiome present in different fractions of the blood of healthy individuals. STUDY DESIGN AND METHODS: The study was conducted in 30 healthy blood donors to the French national blood collection center (Etablissement Francais du Sang). We have set up a 16S rDNA quantitative polymerase chain reaction assay as well as a 16S targeted metagenomics sequencing pipeline specifically designed to analyze the blood microbiome, which we have used on whole blood as well as on different blood fractions (buffy coat [BC], red blood cells [RBCs], and plasma). RESULTS: Most of the blood bacterial DNA is located in the BC (93.74%), and RBCs contain more bacterial DNA (6.23%) than the plasma (0.03%). The distribution of 16S DNA is different for each fraction and spreads over a relatively broad range among donors. At the phylum level, blood fractions contain bacterial DNA mostly from the Proteobacteria phylum (more than 80%) but also from Actinobacteria, Firmicutes, and Bacteroidetes. At deeper taxonomic levels, there are striking differences between the bacterial profiles of the different blood fractions. CONCLUSION: We demonstrate that a diversified microbiome exists in healthy blood. This microbiome has most likely an important physiologic role and could be implicated in certain transfusion-transmitted bacterial infections. In this regard, the amount of 16S bacterial DNA or the microbiome profile could be monitored to improve the safety of the blood supply. PMID- 26865080 TI - A novel subset of enteric neurons revealed by ptf1a:GFP in the developing zebrafish enteric nervous system. AB - The enteric nervous system, the largest division of the peripheral nervous system, is derived from vagal neural crest cells that invade and populate the entire length of the gut to form diverse neuronal subtypes. Here, we identify a novel population of neurons within the enteric nervous system of zebrafish larvae that express the transgenic marker ptf1a:GFP within the midgut. Genetic lineage analysis reveals that enteric ptf1a:GFP(+) cells are derived from the neural crest and that most ptf1a:GFP(+) neurons express the neurotransmitter 5HT, demonstrating that they are serotonergic. This transgenic line, Tg(ptf1a:GFP), provides a novel neuronal marker for a subpopulation of neurons within the enteric nervous system, and highlights the possibility that Ptf1a may act as an important transcription factor for enteric neuron development. PMID- 26865081 TI - Susceptibility profile and epidemiological cut-off values of Cryptococcus neoformans species complex from Argentina. AB - Epidemiological cut-off values (ECVs) based on minimal inhibitory concentration (MIC) distribution have been recently proposed for some antifungal drug/Cryptococcus neoformans combinations. However, these ECVs vary according to the species studied, being serotypes and the geographical origin of strains, variables to be considered. The aims were to define the wild-type (WT) population of the C. neoformans species complex (C. neoformans) isolated from patients living in Argentina, and to propose ECVs for six antifungal drugs. A total of 707 unique C. neoformans isolates obtained from HIV patients suffering cryptococcal meningitis were studied. The MIC of amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole and posaconazole was determined according to the EDef 7.2 (EUCAST) reference document. The MIC distribution, MIC50 , MIC90 and ECV for each of these drugs were calculated. The highest ECV, which included >=95% of the WT population modelled, was observed for flucytosine and fluconazole (32 MUg ml( 1) each). For amphotericin B, itraconazole, voriconazole and posaconazole, the ECVs were: 0.5, 0.5, 0.5 and 0.06 MUg ml(-1) respectively. The ECVs determined in this study may aid in identifying the C. neoformans strains circulating in Argentina with decreased susceptibility to the antifungal drugs tested. PMID- 26865082 TI - A Cognitive-Affective Scale for Hurricane Risk Perception. AB - The aim of this study was to develop a reliable and valid measure of hurricane risk perception. The utility of such a measure lies in the need to understand how people make decisions when facing an evacuation order. This study included participants located within a 15-mile buffer of the Gulf and southeast Atlantic U.S. coasts. The study was executed as a three-wave panel with mail surveys in 2010-2012 (T0 baseline N = 629, 56%; T1 retention N = 427, 75%; T2 retention N = 350, 89%). An inventory based on the psychometric model was developed to discriminate cognitive and affective perceptions of hurricane risk, and included open-ended responses to solicit additional concepts in the T0 survey. Analysis of the T0 data modified the inventory and this revised item set was fielded at T1 and then replicated at T2 . The resulting scales were assessed for validity against existing measures for perception of hurricane risk, dispositional optimism, and locus of control. A measure of evacuation expectation was also examined as a dependent variable, which was significantly predicted by the new measures. The resulting scale was found to be reliable, stable, and largely valid against the comparison measures. Despite limitations involving sample size, bias, and the strength of some reliabilities, it was concluded that the measure has potential to inform approaches to hurricane preparedness efforts and advance planning for evacuation messages, and that the measure has good promise to generalize to other contexts in natural hazards as well as other domains of risk. PMID- 26865083 TI - Does continuous wound infiltration enhance baseline intravenous multimodal analgesia after posterior spinal fusion surgery? A randomized, double-blinded, placebo-controlled study. AB - PURPOSE: There has been a growing interest in continuous local anaesthetic wound infiltration as a non-opioid technique for postoperative pain relief. The impact of this modality on baseline analgesia after spinal fusion surgery has however been inconclusive. We tested whether continuous wound infiltration with ropivacaine can enhance postoperative analgesia compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. METHODS: In this randomized, double-blinded, placebo-controlled study, a multiholed 19 gauge catheter was placed at the end of the surgical procedure through the wound to permit the continuous administration (8 ml/h) of ropivacaine 0.2 % (ropivacaine group; n = 19 patients) or saline (control group; n = 20 patients) during the first 48 postoperative hours (H48). Both groups received intraoperative low-dose ketamine, a combination of acetaminophen, non-steroidal anti-inflammatory drug, and nefopam over the same postoperative period, and morphine delivered by a patient-controlled analgesia (PCA) device. RESULTS: Morphine consumption was comparable between the two groups both at H48, 38 mg (26:52) (median, 25th:75th percentile) (control group) versus 43 mg (19:74) (ropivacaine group), and at H24, 18 mg (16:22) versus 22 mg (9:35) respectively. Pain scores at rest and during mobilization, quality of postoperative sleep, and morphine-related side effects were comparable between the two groups at H24 and H48. CONCLUSION: Our findings indicate that no additional analgesia was provided with continuous wound infiltration of ropivacaine compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01743794. PMID- 26865084 TI - Reduced antioxidant capacity and increased subclinical inflammation markers in prepubescent obese children and their relationship with nutritional markers and metabolic parameters. AB - OBJECTIVE: There are associations between some inflammatory and oxidative markers and obesity in adults, but whether prepubescent children of different weights also have such markers has not been studied. We investigated multiple inflammatory markers and levels of erythrocyte oxidant/antioxidant enzymes in prepubescent children of different weights. METHODS: Children aged 2-11 years were divided into three groups: 80 were underweight, 90 were obese but otherwise healthy, and 80 were healthy age- and sex-matched children of normal-weight. We analyzed inflammatory markers and the total oxidant status, total antioxidant status (TAS), and total thiol level were also determined, and the oxidative stress index was calculated as an indicator of the degree of oxidative stress. RESULTS: The obese group exhibited higher levels of fasting glucose, insulin, total cholesterol, triglycerides, the homeostatic model assessment of insulin resistance (HOMA-IR), and the homeostatic model assessment of beta-cell function (HOMA-beta), C-reactive protein (CRP), neutrophils, and neutrophil/lymphocyte ratio (NLR), as well as lower TAS and total thiol levels than the other two groups (all P < 0.001). Moreover, TAS and total thiols were negatively correlated with age in the obese group (r = -0.212, P = 0.001; r = -0.231, P < 0.001, respectively). CRP levels in plasma were positively correlated with the body mass index (BMI), insulin and glucose levels, HOMA-IR, HOMA-beta, WBC and neutrophil counts, and the NLR, and were negatively correlated with TAS and total thiol levels in the overall studied population. DISCUSSION: The coexistence of increased obesity-related subclinical inflammation and decreased antioxidant capacity can be observed even in prepubescence, and may eventually increase the risk of long-term vascular damage. PMID- 26865087 TI - Histologic Evidence of Melanocytes Isolated to the Nail Matrix. PMID- 26865086 TI - 68Gallium-DOTATATE PET in meningioma: A reliable predictor of tumor growth rate? AB - BACKGROUND: DOTATATE-based radionuclides have added new options in the diagnosis and treatment of meningiomas; however, a reliable predictor of tumor growth has still not been established. METHODS: We analyzed 64 meningiomas imaged with (68)Ga-DOTATATE PET. Tumor growth rates were calculated by volumetric analysis of sequential MRI scans. Maximums of standardized uptake values (SUVmax) were correlated with tumor growth and covariates. RESULTS: World Health Organization (WHO) grades I and II meningiomas showed a correlation of SUVmax and tumor growth rate (meningiomas limited to the intracranial compartment: r = 0.757, P < .001, and transosseous growing meningiomas: r = 0.819, P = .024). SUVmax was significantly higher and the slope of the linear regression significantly steeper in transosseous compared with intracranial meningiomas (both P < .001). The association remained significant in multivariate analysis, and the prediction of tumor growth rate was independent of WHO grade. Anaplastic meningiomas showed no significant correlation of SUVmax and tumor growth. CONCLUSIONS: (68)Ga-DOTATATE PET is a reliable predictor of tumor growth in WHO grades I and II meningiomas and provides additional information to conventional cross-sectional imaging modalities. Hence, (68)Ga-DOTATATE PET can assist in selecting the time point for treatment initiation. Furthermore, meningiomas with fast tumor growth and transosseous expansion elicit the highest DOTATATE binding; therefore, they might be especially suited for DOTATATE-based therapy. PMID- 26865088 TI - General life satisfaction predicts dementia in community living older adults: a prospective cohort study. AB - BACKGROUND: Low life satisfaction predicts adverse outcomes, and may predict dementia. The objectives were: (1) to determine if life satisfaction predicts dementia over a five year period in those with normal cognition at baseline; and (2) to determine if different aspects of life satisfaction differentially predict dementia. METHODS: Secondary analysis of an existing population-based cohort study with initial assessment in 1991 and follow-up five years later. Initially, 1,751 adults age 65+ living in the community were sampled from a representative sampling frame. Of these, 1,024 were alive and had complete data at time 2, of whom 96 were diagnosed with dementia. Life satisfaction was measured using the Terrible-Delightful scale, which measures overall life satisfaction on a 7-point scale, as well as various aspects of life satisfaction (e.g. friendships, finances, etc.) Dementia was diagnosed by clinical examination using DSM-IIIR criteria. Logistic regression models were constructed for the outcome of dementia at time 2, and adjusted for age, gender, education, and comorbidities. RESULTS: Overall life satisfaction predicted dementia five years later, at time 2. The unadjusted Odds Ratio (OR; 95% confidence interval) for dementia at time 2 was 0.72 (0.55, 0.95) per point. The adjusted OR for dementia was 0.70 (0.51, 0.96). No individual item on the life satisfaction scale predicted dementia. However, the competing risk of mortality was very high for some items. CONCLUSION: A global single-item measure of life satisfaction predicts dementia over a five year period in older adults without cognitive impairment. PMID- 26865085 TI - The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders? AB - The gut-brain axis is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior. PMID- 26865089 TI - Wnt5a inhibited human trophoblast cell line HTR8/SVneo invasion: implications for early placentation and preeclampsia. AB - OBJECTIVE: Wnt5a and Wnt signaling play potential roles in human placental and fetal development. The objective of this study is to explore the role of Wnt5a in the invasion of the human trophoblast cell line HTR8/SVneo and the probable mechanism of early placentation and preeclampsia in which Wnt5a is involved. METHODS: Human first trimester villous tissues from normal pregnancies and third trimester placentas from pregnancies with or without preeclampsia (PE) were used in the detection of the expression and subcellular location of Wnt5a. The human trophoblast cell line HTR8/SVneo was treated with 0-400 ng/ml recombinant Wnt5a to investigate the role of Wnt5a in human trophoblast invasion. RESULTS: Human first trimester villous is accompanied by the decreased expression of Wnt5a compared with term placenta. Upregulated Wnt5a was detected in PE placenta compared with the normal control. Wnt5a inhibited the migration and invasion of HTR8/SVneo cells with decreased integrin beta1, alpha5 and N-cadherin. Moreover, Wnt5a downregulated beta-catenin in HTR8/SVneo cells. CONCLUSIONS: These findings strongly suggest that Wnt5a inhibits the invasion of HTR8/SVneo cells. Decreased Wnt5a facilitates early placentation, whereas increased Wnt5a contributes to the pathogenesis of PE with insufficient trophoblast invasion. Aberrant Wnt5a may function by impairing Wnt non-canonical/beta-catenin signaling pathway in trophoblasts. PMID- 26865090 TI - Abscisic acid promotes proteasome-mediated degradation of the transcription coactivator NPR1 in Arabidopsis thaliana. AB - Proteasome-mediated turnover of the transcription coactivator NPR1 is pivotal for efficient activation of the broad-spectrum plant immune responses known as localized acquired resistance (LAR) and systemic acquired resistance (SAR) in adjacent and systemic tissues, respectively, and requires the CUL3-based E3 ligase and its adaptor proteins, NPR3 and NPR4, which are receptors for the signaling molecule salicylic acid (SA). It has been shown that SA prevents NPR1 turnover under non-inducing and LAR/SAR-inducing conditions, but how cellular NPR1 homeostasis is maintained remains unclear. Here, we show that the phytohormone abscisic acid (ABA) and SA antagonistically influence cellular NPR1 protein levels. ABA promotes NPR1 degradation via the CUL3(NPR) (3/) (NPR) (4) complex-mediated proteasome pathway, whereas SA may protect NPR1 from ABA promoted degradation through phosphorylation. Furthermore, we demonstrate that the timing and strength of SA and ABA signaling are critical in modulating NPR1 accumulation and target gene expression. Perturbing ABA or SA signaling in adjacent tissues alters the temporal dynamic pattern of NPR1 accumulation and target gene transcription. Finally, we show that sequential SA and ABA treatment leads to dynamic changes in NPR1 protein levels and target gene expression. Our results revealed a tight correlation between sequential SA and ABA signaling and dynamic changes in NPR1 protein levels and NPR1-dependent transcription in plant immune responses. PMID- 26865091 TI - Hydrophilic GO/Fe3O4/Au/PEG nanocomposites for highly selective enrichment of glycopeptides. AB - GO/Fe3O4/Au/PEG nanocomposites were synthesized via bonding gold nanoparticles on magnetic graphene oxide using polyethylenimine as the reducing and immobilizing reagent, followed by thiol-terminal polyethylene glycol immobilization. With the use of this nanocomposite, 255 glycopeptides, mapped to 127 different glycoproteins, were identified from human serum, demonstrating its great potential for glycosylation analysis. PMID- 26865093 TI - Hope is a four-letter word: riding the emotional rollercoaster of illness management. AB - In this autoethnography, I explore the process and emotional experience of trying a new drug to improve my quality of life. In so doing, I synthesise personal history with extant research on chronic illness by analysing ways in which my experiences reflect and reject social norms. I also incorporate perspectives from research on aspirations and attainment, and the mental health consequences of cyclical disappointment. By weaving together lessons from each of these literatures, I articulate an integrative psychosocial understanding of the micro level processes and experiences involved in illness management as well as the ways that experiences of illness management may require integration of varied sociological insights concerning health. In closing, I draw out theoretical implications for understanding the integration and variation of insights from many areas of health research in the lived experiences of people with chronic conditions. A Virtual Abstract of this article can be seen at: https://youtu.be/5aoaWGItDgM. PMID- 26865094 TI - A Systematic Cell-Based Analysis of Localization of Predicted Drosophila Peroxisomal Proteins. AB - Peroxisomes are membrane-bound organelles found in almost all eukaryotic cells. They perform specialized biochemical functions that vary with organism, tissue or cell type. Mutations in human genes required for the assembly of peroxisomes result in a spectrum of diseases called the peroxisome biogenesis disorders. A previous sequence-based comparison of the predicted proteome of Drosophila melanogaster (the fruit fly) to human proteins identified 82 potential homologues of proteins involved in peroxisomal biogenesis, homeostasis or metabolism. However, the subcellular localization of these proteins relative to the peroxisome was not determined. Accordingly, we tested systematically the localization and selected functions of epitope-tagged proteins in Drosophila Schneider 2 cells to determine the subcellular localization of 82 potential Drosophila peroxisomal protein homologues. Excluding the Pex proteins, 34 proteins localized primarily to the peroxisome, 8 showed dual localization to the peroxisome and other structures, and 26 localized exclusively to organelles other than the peroxisome. Drosophila is a well-developed laboratory animal often used for discovery of gene pathways, including those linked to human disease. Our work establishes a basic understanding of peroxisome protein localization in Drosophila. This will facilitate use of Drosophila as a genetically tractable, multicellular model system for studying key aspects of human peroxisome disease. PMID- 26865095 TI - Cutaneous Manifestations of Thymoma-associated Multi-organ Autoimmunity: A Fatal Sign. PMID- 26865097 TI - Selective binding modes and allosteric inhibitory effects of lupane triterpenes on protein tyrosine phosphatase 1B. AB - Protein Tyrosine Phosphatase 1B (PTP1B) has been recognized as a promising therapeutic target for treating obesity, diabetes, and certain cancers for over a decade. Previous drug design has focused on inhibitors targeting the active site of PTP1B. However, this has not been successful because the active site is positively charged and conserved among the protein tyrosine phosphatases. Therefore, it is important to develop PTP1B inhibitors with alternative inhibitory strategies. Using computational studies including molecular docking, molecular dynamics simulations, and binding free energy calculations, we found that lupane triterpenes selectively inhibited PTP1B by targeting its more hydrophobic and less conserved allosteric site. These findings were verified using two enzymatic assays. Furthermore, the cell culture studies showed that lupeol and betulinic acid inhibited the PTP1B activity stimulated by TNFalpha in neurons. Our study indicates that lupane triterpenes are selective PTP1B allosteric inhibitors with significant potential for treating those diseases with elevated PTP1B activity. PMID- 26865099 TI - Physicians' attitudes towards androgen replacement therapy for male and female sexual dysfunction. AB - Androgen deficiency syndrome is a commonly diagnosed condition. The aim of this study was to investigate common clinical practices of specialists in the field of sexual medicine regarding androgen replacement treatment for men and women. Attendees of the 16th Annual Congress of the European Society of Sexual Medicine held in January 2014 in Istanbul, Turkey, were asked to participate in a survey during the congress days. A 24-item self-report, closed-question questionnaire was distributed. Three sections were accessed: sociodemographic data, professional background and personal practice patterns regarding androgen substitution in men and women. A total of 133 physicians (mean age 47 years; range 25-79) completed the survey. Responses were inconsistent regarding the lab tests used for primary evaluation of male androgen deficiency. The majority of participants (62%) recommended testosterone replacement therapy for symptomatic men with testosterone levels <8 nmol l(-1) (231 ng dl(-1)). Similarly, most physicians (88%) recognized a correlation between libido and testosterone levels in women. Only 42% and 53% reported they would prescribe testosterone to women with low libido, premenopausal and postmenopausal, respectively. This survey showed discrepancies among physicians regarding testosterone replacement therapy for men and women. PMID- 26865098 TI - Lessons learned from cancer prevention studies with nutrients and non-nutritive dietary constituents. AB - Epidemiological studies have observed the association between dietary patterns and the risk of certain types of cancer. Extensive studies have been conducted on the cancer preventive activities of constituents from food and beverages. While laboratory research has shown impressive and promising results, such promising cancer preventive activities have not been demonstrated in many human intervention trials. This article analyzes the major differences between these different types of studies and the limitations of these studies. Animal and cell line studies usually use optimal conditions in order to demonstrate the hypothesized effects, sometimes without considering the human relevance. On the other hand, some clinical trials were designed without a good understanding of the biochemical and pharmacological properties of the agents used. Lessons learned from these studies will be illustrated using vitamin E, beta-carotene and selenium as examples for nutrients, and green tea polyphenols as an example for non-nutritive dietary constituents. From the lessons learned, we believe that more interdisciplinary collaboration and integration of laboratory and human studies would effectively advance the field of cancer prevention. PMID- 26865100 TI - Erectile dysfunction in patients with plaque psoriasis: the relation of depression and cardiovascular factors. AB - Psoriasis is a chronic inflammatory skin disease and seems to be associated with erectile dysfunction (ED). ED is a predictor of future cardiovascular disease. It is important to identify ED early and investigate cardiovascular problems in psoriasis patients. The sample consisted of 191 psoriasis patients and 191 healthy men. One hundred and one of 191 (52.9%) patients with psoriasis were indicative of ED, compared with 40.3% in control group, reflecting an age adjusted odds ratio of 1.965 in favor of the psoriasis group. A univariate analysis in the psoriasis group indicated that age, hypertension, hyperlipidemia, diabetes mellitus and depressive symptoms were the risk factors for ED. The multivariate logistic regression model indicated that increasing age, hypertension, hyperlipidemia and depressive symptoms were independent risk factors for ED in psoriasis. The more severe depressive symptoms increased the risk of ED and especially moderate-severe ED. The diagnosis of ED may help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of ED may become a part of routine care in the management of psoriasis patients. PMID- 26865101 TI - Premature ejaculation results from partners' mismatch: development and validation of index of intra-vaginal ejaculation latency time. AB - Mismatch of partners in premature ejaculation (PE) regarding intra-vaginal ejaculation latency time (IELT) is usually neglected. Here we proposed the concept and evaluated the use of index of IELT (IIELT) as an objective diagnostic tool for PE. Data from 103 self-reporting PE patients and 59 normal controls were collected. The expected IELTs of both the male and female partners were provided by each participating couple in two questionnaires. IIELT=stopwatch IELT/(1/2 the male's expected IELT+1/2 the female's expected IELT). The stopwatch IELTs were 1.74+/-1.4 min (PE group) and 14.45+/-11.0 min (control group), P<0.05. The expected IELTs were 15.65+/-8.7 min (men) and 14.16+/-6.9 min (women) in the PE group, and 21.3+/-16.1 min (men) and 20.04+/-13.47 min (women) in the control group, P<0.05. The calculated IIELTs were 0.14+/-0.12 (PE group) and 0.83+/-0.60 (control group), P<0.05. The best cut-off point was 0.658, the Youden index was 0.652, sensitivity was 0.991, specificity was 0.661, positive predictive probability was 83.46% and negative predictive probability was 97.6%. We concluded that IIELT was an integrated measurement of the couples' sexual equilibrium and demonstrated that it provided a simple and objective screening indicator for diagnosing self-reported PE. PMID- 26865102 TI - Sexual quality of life is impaired in patients with chronic hepatitis C. AB - Chronic hepatitis C (CHC) patients often have altered quality of life. Few data are available about sexual impairment (SI) in CHC. From 2011 to 2013, we included consecutive CHC outpatients. Exclusion criteria were: antiviral therapy, co infection, age <18 or >75, transplantation, alcohol consumption, Eastern Cooperative Oncology Group >1. Non-CHC subjects were healthy blood donors. Sexual questionnaires for men and women were adapted from the International Index of Erectile Function and Female Sexual Function Index, respectively, and concerned the past 30 days. Two hundred eighty-one patients were compared with 1086 blood donors. SI was more frequent in CHC patients. Men with CHC had worse desire, confidence, erections, climax and satisfaction (P<0.001). Women with CHC had worse desire, arousal, climax, satisfaction, lubrication and comfort (P<0.001). In multivariate analysis, factors associated with SI in men were CHC (odds ratio (OR)=4.45, 95% confidence interval (CI) 2.46-8.06), age (OR=1.06, 95% CI 1.03 1.09), no intercourse (OR=8.74, 95% CI 4.65-16.04) and unemployment (OR=2.14, 95% CI 1.16-3.95). Factors associated with a worse global sexual life in women were CHC (OR=7.96, 95% CI 4.07-15.58) and no intercourse (OR=21.39, 95% CI 11.03 41.48). The study results were corroborated by propensity score-matching analysis. Sexual life is impaired in men and women with CHC. In clinical practice, sexual quality of life should be evaluated and treated. PMID- 26865103 TI - Risk factors associated with sexual dysfunction in Brazilian postmenopausal women. AB - Sexual function represents an important component of health and life quality. The objective of this study was to assess female sexual function in postmenopausal women and to identify factors associated with sexual dysfunction among this population. From August to December 2013 a cross-sectional study was carried out with 111 postmenopausal, sexually active women aged 45-65 years. A semi structured questionnaire made up of itemized questions was applied to identify demographic variables, socio-economic and clinical issues. Participants were requested to fill out the Female Sexual Function Index (FSFI) and the Menopause Rating Scale. Among the studied group, 70.3% of the women presented sexual dysfunction (FSFI?26.6). The affected domains were desire and arousal (P<0.01). Multiple regression analysis revealed that the main risk factors associated with postmenopausal sexual dysfunction were: marital status (prevalence ratio (PR) 1.67; 95% confidence interval (CI) 1.17-2.39; P<0.01), urogenital dysfunction (PR 1.08; 95% CI 1.03-1.12; P<0.00), bladder surgery (PR 1.35; 95% CI 1.09-1.66; P<0.01) and sexual abuse (PR 1.45; 95% CI 1.21-1.72; P<0.00). Our results show a high female sexual dysfunction among postmenopausal women. Sexual dysfunction was associated with multiple factors such as: socio-demographic factors, biological factors (urogenital dysfunctions, bladder surgery), psychological matters and sexual abuse. PMID- 26865104 TI - Prevalence and risk factors for erectile dysfunction and lower urinary tract symptoms in Russian Federation men: analysis from a national population-based multicenter study. AB - An analysis of prevalence and associated common risk factors of ED and lower urinary tract symptoms (LUTS) was performed in Russian Federation by cross sectional multicenter survey. International Index of Erectile Function (IIEF) score and International Prostate Symptom Score (IPSS) were used for data collection in 1225 men between 20 and 77 years interviewed in six regions of Russian Federation. In addition, each participant's social, demographic, lifestyle, sexual and medical history was taken with special emphasis on risk factors for ED. Upon the basis of IIEF erectile domain score interpretation, ED was found in 530 (48.9%) men, consisting of mild and mild to moderate, moderate and severe ED in 375 (34.6%), 78 (7.2%) and 77 (7.1%) respondents, respectively. According to IPSS assessment, LUTSs were present in 649 (59.9%) responders; inclusive 370 (34.2%), 216 (19.9%) and 63 (5.8%) men with mild, moderate and severe LUTS, respectively. Men with both ED and LUTS shared common co-morbidities and lifestyle risk factors with age-adjusted odds ratio between 1.2 and 5.2. In logistic regression model (R(2)=0.361), the strongest associated with ED factor found was IPSS symptom score, followed by hypertension, IPSS-related quality of life, age, diabetes mellitus, obesity and unmotivated fatigue. PMID- 26865106 TI - Consensus Planning Toward a Community-Based Approach to Promote Physical Activity in Youth with Cerebral Palsy. AB - AIMS: To engage researchers and knowledge-users in six Ontario communities in knowledge translation initiatives to identify community-informed elements to guide the development of an optimal physical activity program for youth with cerebral palsy (CP) and to support research efforts. METHODS: The project included three iterative steps, i.e., an environmental scan of five communities, six regional planning meetings, and a member-checking survey, followed by a Delphi survey to reach consensus on the elements deemed most important. RESULTS: Twenty-four elements were identified to include in programs promoting physical activity in youth with CP, which were organized in five categories: raise awareness of the options and opportunities (n = 4); pique interest and motivate youth to become and stay active (n = 9); ensure community programs are ready for youth with a disability (n = 2); be fit, fit in, and finding the best fit (n = 5); and explore the layers of physical activity and how they interact (n = 4). CONCLUSIONS: The 24 elements established characterize the key concepts that families and community stakeholders value when developing physical activity programs for youth with CP. When incorporated into clinical practice, each of the elements may be used to evaluate key aspects of outcome for individuals with CP. PMID- 26865107 TI - Spirometric reference equations for Swedish adults. AB - New spirometric reference equations for Swedish adults are required. Three different older sets of reference equations clinically used in Sweden have various drawbacks and the recently published 'The Global Lung Function 2012 (GLI) equations' have been shown not to be adequate for Swedish normal, healthy non smokers. We have recently concluded that a piecewise linear model presented by Lubinski and Golczewski accurately describes the distribution of spirometric variables in a large Swedish random population sample. This piecewise linear model also offers the important advantage of implementing easily physiologically interpretable coefficients. The present study aimed at presenting piecewise linear reference equations for Swedish adults based on a random population sample of 6685 individuals aged 25-75 years. Predicted normal values by the piecewise linear reference equations and lower limit normal (LLN) were compared with the three reference equations frequently used clinically in Sweden and the GLI equations. We found predicted normal values according to the present piecewise linear reference equations close to 100% predicted normal as expected, whereas the other equations either overestimated or underestimated normal subjects. Concerning LLN, the present equations, i.e. 1.645 * RSD, showed the least deviation from the expected 5% and, e.g., the GLI equations systematically identified too few subjects below LLN. We conclude that the present piecewise linear reference equations, based on a relatively large general population sample, ought to be considered for clinical use in Sweden. Application of 1.645 * RSD below predicted value gave an acceptably accurate LLN. PMID- 26865108 TI - Control of Conformation and Chirality of Nonplanar pi-Conjugated Diporphyrins Using Substituents and Axial Ligands. AB - Nonplanar conformations of pyrazine-fused Zn(II) diporphyrins could be controlled by the choice of the meso-aryl substituents and an axial ligand on the central metals. Zn(II) diporphyrins bearing sterically demanding meso-aryl groups with ortho-substituents led to a twisted chiral D2 conformation, while an achiral C2h form was preferred in the case of aryl groups without ortho-substituents. Helical chirality induction on Zn(II) diporphyrins in the twisted conformation was achieved by controlling their handedness of the molecular twist through coordination of optically active 1-phenethylamine. PMID- 26865105 TI - Modular Assembly Approach to Engineer Geometrically Precise Cardiovascular Tissue. AB - This modular assembly approach to microfabricate functional cardiovascular tissue composites enables quantitative assessment of the effects of microarchitecture on cellular function. Cardiac and endothelial modules are micromolded separately, designed to direct cardiomyocyte alignment and anisotropic contraction or vascular network formation. Assembled cardiovascular tissue composites contract synchronously, facilitating the use of this tissue-engineering platform to study structure-function relationships in the heart. PMID- 26865109 TI - Inflammation: A20-NEMO interaction prevents autoinflammation. PMID- 26865110 TI - Degradation of the long-resistant pharmaceutical compounds carbamazepine and diatrizoate using mixed microbial culture. AB - The microbial degradation of two recalcitrant pharmaceutical compounds, carbamazepine (CBZ) and diatrizoate (DTZ), was studied in laboratory batch experiments. We used a defined mixed microbial culture comprising four distinct microbial species that were previously known to have high decomposition capacity toward recalcitrant substances. Biological decomposition in liquid phase cultures for either CBZ or DTZ, or in a combination of the two, was conducted for 12 days. DTZ and CBZ were degraded by 43.2% and 60%, respectively from an initial concentration of 100 ug L(-1). When degradation was assessed using a mixture of the two compounds, the initial degradation rates of CBZ and DTZ were lower than those observed in the single-compound study. However, the final cumulative removal efficiency was very similar. The extent of dissolved organic carbon (DOC) removal was correlated with the degradation of the pharmaceuticals. PMID- 26865112 TI - 7-(Benzofuran-2-yl)-7-deazadeoxyguanosine as a fluorescence turn-ON probe for single-strand DNA binding protein. AB - 7-(Benzofuran-2-yl)-7-deazadeoxyguanosine ((BF)dG) was synthesized and incorporated into an oligodeoxynucleotide (ODN). The single-stranded ODN containing (BF)dG shows 91-fold fluorescence enhancement upon binding of single strand DNA binding protein. PMID- 26865113 TI - Identification of Palmitoylated Transitional Endoplasmic Reticulum ATPase by Proteomic Technique and Pan Antipalmitoylation Antibody. AB - Protein palmitoylation plays a significant role in a wide range of biological processes such as cell signal transduction, metabolism, apoptosis, and carcinogenesis. For high-throughput analysis of protein palmitoylation, approaches based on the acyl-biotin exchange or metabolic labeling of azide/alkynyl-palmitate analogs are commonly used. No palmitoylation antibody has been reported. Here, the palmitoylated proteome of human colon cancer cell lines SW480 was analyzed via a TS-6B-based method. In total, 151 putative palmitoylated sites on 92 proteins, including 100 novel sites, were identified. Except for 3 known palmitoylated transmembrane proteins, ATP1A1, ZDHHC5, and PLP2, some important proteins including kinases, ion channels, receptors, and cytoskeletal proteins were also identified, such as CLIC1, PGK1, PPIA, FKBP4, exportin-2, etc. More importantly, the pan antipalmitoylation antibody was developed and verified for the first time. Our homemade pan antipalmitoylation antiserum could differentiate well protein palmitoylation from mouse brain membrane fraction and SW480 cells, which affords a new technique for analyzing protein palmitoylation by detecting the palmitic acid moiety directly. Furthermore, the candidate protein transitional endoplasmic reticulum ATPase (VCP) identified in SW480 cells was validated to be palmitoylated by Western blotting with anti-VCP antibody and the homemade pan antipalmitoylation antibody. PMID- 26865111 TI - Temporal retinal transcriptome and systems biology analysis identifies key pathways and hub genes in Staphylococcus aureus endophthalmitis. AB - Bacterial endophthalmitis remains a devastating inflammatory condition associated with permanent vision loss. Hence, assessing the host response in this disease may provide new targets for intervention. Using a mouse model of Staphylococcus aureus (SA) endophthalmitis and performing retinal transcriptome analysis, we discovered progressive changes in the expression of 1,234 genes. Gene ontology (GO) and pathway analyses revealed the major pathways impacted in endophthalmitis includes: metabolism, inflammatory/immune, antimicrobial, cell trafficking, and lipid biosynthesis. Among the immune/inflammation pathways, JAK/Stat and IL-17A signaling were the most significantly affected. Interactive network-based analyses identified 13 focus hub genes (IL-6, IL-1beta, CXCL2, STAT3, NUPR1, Jun, CSF1, CYR61, CEBPB, IGF-1, EGFR1, SPP1, and TGM2) within these important pathways. The expression of hub genes confirmed by qRT-PCR, ELISA (IL-6, IL 1beta, and CXCL2), and Western blot or immunostaining (CEBP, STAT3, NUPR1, and IGF1) showed strong correlation with transcriptome data. Since TLR2 plays an important role in SA endophthalmitis, counter regulation analysis of TLR2 ligand pretreated retina or the use of retinas from TLR2 knockout mice showed the down regulation of inflammatory regulatory genes. Collectively, our study provides, for the first time, a comprehensive analysis of the transcriptomic response and identifies key pathways regulating retinal innate responses in staphylococcal endophthalmitis. PMID- 26865114 TI - Population-based cohort study of the management and survival of patients with early-stage oesophageal adenocarcinoma in England. AB - BACKGROUND: Until recently, oesophagectomy was the treatment of choice for early oesophageal cancer. Endoscopic treatment has been introduced relatively recently. This observational national database study aimed to describe how endoscopic therapy has been introduced in England and to examine the safety of this approach. METHODS: A population-based cohort study was undertaken of patients diagnosed with oesophageal adenocarcinoma between October 2007 and June 2009 using three linked national databases. Patients with early-stage disease (T1 tumours with no evidence of spread) were identified, along with the primary treatment modality where treatment intent was curative. Short-term outcomes after treatment and 5-year survival were evaluated. RESULTS: Of 5192 patients diagnosed with oesophageal adenocarcinoma, 306 (5.9 per cent) were considered to have early stage disease before any treatment, of whom 239 (79.9 per cent of 299 patients with data on treatment intent) were managed with curative intent. Of 175 patients who had an oesophagectomy, 114 (65.1 (95 per cent c.i. 57.6 to 72.7) per cent) survived for 5 years. Among these, 47 (30.3 per cent of 155 patients with tissue results available) had their disease upstaged after pathological staging; this occurred more often in patients who did not have staging endoscopic ultrasonography before surgery. Of 41 patients who had an endoscopic resection, 27 (66 (95 per cent c.i. 49 to 80) per cent) survived for 5 years. Repeat endoscopic therapy was required by 23 (56 per cent) of these 41 patients. CONCLUSION: Between 2007 and 2009, oesophagectomy remained the initial treatment of choice (73.2 per cent) among patients with early-stage oesophageal cancer treated with curative intent; one in five patients were managed endoscopically, and this treatment was more common in elderly patients. Although the groups had different patient characteristics, 5-year survival rates were similar. PMID- 26865115 TI - Cystic fibrosis bronchial epithelial cells have impaired ability to activate vitamin D. PMID- 26865116 TI - Multifunctional flexible free-standing titanate nanobelt membranes as efficient sorbents for the removal of radioactive (90)Sr(2+) and (137)Cs(+) ions and oils. AB - For the increasing attention focused on saving endangered environments, there is a growing need for developing membrane materials able to perform complex functions such as removing radioactive pollutants and oil spills from water. A major challenge is the scalable fabrication of membranes with good mechanical and thermal stability, superior resistance to radiation, and excellent recyclability. In this study, we constructed a multifunctional flexible free-standing sodium titanate nanobelt (Na-TNB) membrane that was assembled as advanced radiation tainted water treatment and oil uptake. We compared the adsorption behavior of (137)Cs(+) and (90)Sr(2+) on Na-TNB membranes under various environmental conditions. The maximum adsorption coefficient value (Kd) for Sr(2+) reaches 10(7) mL g(-1). The structural collapse of the exchange materials were confirmed by XRD, FTIR and XPS spectroscopy as well as Raman analysis. The adsorption mechanism of Na-TNB membrane is clarified by forming a stable solid with the radioactive cations permanently trapped inside. Besides, the engineered multilayer membrane is exceptionally capable in selectively and rapidly adsorbing oils up to 23 times the adsorbent weight when coated with a thin layer of hydrophobic molecules. This multifunctional membrane has exceptional potential as a suitable material for next generation water treatment and separation technologies. PMID- 26865117 TI - Clinical and genetic features of lysinuric protein intolerance in Japan. AB - BACKGROUND: Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acid caused by mutations in solute carrier family 7 amino acid transporter light chain, y+ L system, member 7 (SLC7A7). This disorder occurs worldwide, especially in Finland and Japan, where founder effect mutations have been reported. Detailed features of the clinical symptoms and mutation types in Japanese LPI, however, remain unclear to date. METHODS: An epidemiological nationwide survey of LPI patients was carried out via mail to all domestic university and general hospitals in Japan. Next, the clinical information for each LPI patient was obtained, in the form of a questionnaire, from the attending physicians who replied to the letters. RESULTS: We received answered questionnaires for 43 LPI patients in 19 hospitals. We selected 35 patients who were genetically diagnosed with LPI. The most common clinical manifestations were with protein aversion, ferritinemia, increased serum lactate dehydrogenase, and hyperammonemia. The most frequent SLC7A7 mutation in Japanese LPI patients is p.R410*, which is a founder effect mutation in northern Japan. In total, nine types of mutation were detected in this survey, six of which (p.R410*, p.S238F, c.1630delC, p.S489P, c.1673delG, and IVS3-IVS5del9.7 kb) have not been reported in other countries. CONCLUSION: The clinical and genetic features of 35 Japanese patients with LPI were characterized, and no correlation between genotype and phenotype was observed. The importance of early diagnosis for better prognosis of LPI is emphasized. PMID- 26865118 TI - A mosaic Lauralean flower from the Early Cretaceous of Myanmar. AB - PREMISE OF THE STUDY: The floral history of early angiosperms is far from complete. The fossil discussed here has the potential to expand our knowledge of timing, reproductive biology, and paleobiogeography in early angiosperms. METHODS: Cutting-edge methodologies in CT scanning in conjunction with tomography software have opened new possibilities for discovering details in amber-preserved fossils that were inaccessible for meaningful study in the past. KEY RESULTS: The fossil is small and complex, cupulate, with numerous stamens and a suite of characters distributed in the modern families of Laurales. The most parsimonious placement of the fossil based on morphology is as a sister taxon of Atherospermataceae + Gomortega (Gomortegaceae). CONCLUSIONS: This fossil taxon, a Laurasian Lauralean from the mid-Cretaceous, is an important example of fossil Laurales with implications for biogeography and timing in the radiation and extinction in this group. PMID- 26865119 TI - New frontiers in the three-dimensional visualization of plant structure and function. PMID- 26865120 TI - Flower-visitor selection on floral integration in three contrasting populations of Lonicera implexa. AB - PREMISE OF THE STUDY: Geographic differences in flower visitor assemblages might lead to among-population differences in the magnitude and pattern of floral integration. However, the role of current pollinator visitation in shaping the magnitude and pattern of floral trait correlations is still controversial. METHODS: We used individual-level data on floral morphology, flower visitation, and fitness to assess if floral integration (at flower and floral-module level) and the covariance structure of floral traits varied among three populations of Lonicera implexa differing in the importance of long-tongue (hawk moths) and short-tongue (bees and small beetles) pollinators; and to assess whether this variation was related to the selection pressures exerted by flower visitors. KEY RESULTS: Short-tongue pollinators preferentially visited plants with floral traits that enhanced flower accessibility; consequently, there was directional selection for accessibility (integration at floral-module level) in the populations where they dominated or codominated. In the population with both short- and long-tongue pollinators, disruptive selection on corolla width and directional selection against whole-flower integration was also found. Dominance by long-tongue pollinators (hawk moths) resulted in disruptive selection on whole flower integration. Overall, the conflicting selection pressures that were found matched among-population differences in covariance structure: populations with short-tongue pollinators showed correlations between corolla-tube width and other floral traits that were absent in the population pollinated primarily by hawk moths. CONCLUSIONS: Conflicting selection on floral integration mediated by floral visitors can occur even in nearby populations of a species with restricted floral morphology. PMID- 26865121 TI - A global perspective on Campanulaceae: Biogeographic, genomic, and floral evolution. AB - PREMISE OF THE STUDY: The Campanulaceae are a diverse clade of flowering plants encompassing more than 2300 species in myriad habitats from tropical rainforests to arctic tundra. A robust, multigene phylogeny, including all major lineages, is presented to provide a broad, evolutionary perspective of this cosmopolitan clade. METHODS: We used a phylogenetic framework, in combination with divergence dating, ancestral range estimation, chromosome modeling, and morphological character reconstruction analyses to infer phylogenetic placement and timing of major biogeographic, genomic, and morphological changes in the history of the group and provide insights into the diversification of this clade across six continents. KEY RESULTS: Ancestral range estimation supports an out-of-Africa diversification following the Cretaceous-Tertiary extinction event. Chromosomal modeling, with corroboration from the distribution of synonymous substitutions among gene duplicates, provides evidence for as many as 20 genome-wide duplication events before large radiations. Morphological reconstructions support the hypothesis that switches in floral symmetry and anther dehiscence were important in the evolution of secondary pollen presentation mechanisms. CONCLUSIONS: This study provides a broad, phylogenetic perspective on the evolution of the Campanulaceae clade. The remarkable habitat diversity and cosmopolitan distribution of this lineage appears to be the result of a complex history of genome duplications and numerous long-distance dispersal events. We failed to find evidence for an ancestral polyploidy event for this clade, and our analyses indicate an ancestral base number of nine for the group. This study will serve as a framework for future studies in diverse areas of research in Campanulaceae. PMID- 26865122 TI - Fruits and wood of Parinari from the early Miocene of Panama and the fossil record of Chrysobalanaceae. AB - PREMISE OF THE STUDY: Chrysobalanaceae are woody plants with over 500 species in 20 genera. They are among the most common trees in tropical forests, but a sparse fossil record has limited our ability to test evolutionary and biogeographic hypotheses, and several previous reports of Chrysobalanaceae megafossils are doubtful. METHODS: We prepared fossil endocarps and wood collected from the lower Miocene beds along the Panama Canal using the cellulose acetate peel technique and examined them using light microscopy. We compared the fossil endocarps with previously published fossils and with fruits from herbarium specimens. We compared the fossil wood with photographs and descriptions of extant species. KEY RESULTS: Parinari endocarps can be distinguished from other genera within Chrysobalanaceae by a suite of features, i.e., thick wall, a secondary septum, seminal cavities lined with dense, woolly trichomes, and two ovate to lingulate basal germination plugs. Fossil endocarps from the Cucaracha, Culebra, and La Boca Formations confirm that Parinari was present in the neotropics by the early Miocene. CONCLUSIONS: The earliest unequivocal evidence of crown-group Chrysobalanaceae is late Oligocene-early Miocene, and the genus Parinari was distinct by at least 19 million years ago. Parinari and other Chrysobalanaceae likely reached the neotropics via long-distance dispersal rather than vicariance. The presence of Parinari in the Cucaracha flora supports the interpretation of a riparian, moist tropical forest environment. Parinari was probably a canopy dominant tree in the Cucaracha forest and took advantage of the local megafauna for seed dispersal. PMID- 26865123 TI - Root development and structure in seedlings of Ginkgo biloba. AB - PREMISE OF THE STUDY: The popular, highly recognizable, well-known gymnosperm, Ginkgo biloba, was studied to document selected developmental features, which are little known in its primary root system from root tips to cotyledonary node following seed germination. METHODS: Using seedlings grown in soil, vermiculite, or a mixture, we examined sections at various distances from the root cap to capture a developmental sequence of anatomical structures by using standard brightfield, epifluorescence, and confocal microscopic techniques. KEY RESULTS: The vascular cylinder is usually a diarch stele, although modified diarchy and triarchy are found. Between exarch protoxylem poles, metaxylem usually develops into a complete disc, except near the transition region, which has irregularly arranged tracheary cells. The disc of primary xylem undergoes secondary growth on its metaxylem flanks with many tracheids added radially within a few weeks. Production of fibers in secondary phloem also accompanies secondary growth. In the cortex, endodermis produces Casparian bands early in development and continues into the upper transition region. Phi cells with phi-thickenings (bands of lignified walls) of a layer of inner cortex are often evident before endodermis, and then adjoining, additional layers of cortex develop phi cells; phi cells do not occur in the upper transition region or stem. An exodermis is produced early in root development and is continuous into the transition region and cotyledonary node. CONCLUSIONS: Seedling root axes of Ginkgo biloba are more complex than the literature suggests, and our findings contribute to our knowledge of root structure of this ancient gymnosperm. PMID- 26865124 TI - Lilies at the limit: Variation in plant-pollinator interactions across an elevational range. AB - PREMISE OF THE STUDY: Many studies assume climatic factors are paramount in determining species' distributions, however, biotic interactions may also play a role. For example, pollinators may limit species' ranges if floral abundance or floral attractiveness is reduced at range margins, thus causing lower pollinator visitation and reduced reproductive output. METHODS: To test if pollinators influence the altitudinal distribution of Erythronium montanum (Liliaceae) at Mount Rainier National Park, we asked whether (1) seed production in this species relies on pollinators, (2) seed production and pollen limitation is greatest at range limits, and (3) pollinator visitation rates (either overall or by individual taxonomic groups) reflect patterns of seed production and pollen limitation. RESULTS: From this three-year study, we established that this plant does rely on pollinators for fruit set and we found that pollen limitation trended toward being higher at the upper range limit in some years, but not consistently year to year. Insect visitation rates did not mirror spatial patterns of pollen limitation, but annually variable pollinator composition suggested differential importance of some pollinator taxonomic groups (specifically, bumblebees may be better pollinators than syrphid flies). CONCLUSIONS: Overall, these results suggest that while pollinators are critical for the reproductive success of this high mountain wildflower, plant-pollinator interactions do not obviously drive the distribution of this species. Nonetheless, high spatio-temporal variability in range-wide plant-pollinator dynamics may complicate responses to climate change. PMID- 26865125 TI - Does total intravenous anesthesia provide significant blood loss reduction compared to inhalational anesthesia during endoscopic sinus surgery? PMID- 26865126 TI - Legionella thermalis sp. nov., isolated from hot spring water in Tokyo, Japan. AB - Strain L-47(T) of a novel bacterial species belonging to the genus Legionella was isolated from a sample of hot spring water from Tokyo, Japan. The 16S rRNA gene sequences (1477 bp) of this strain (accession number AB899895) had less than 95.0% identity with other Legionella species. The dominant fatty acids of strain L-47(T) were a15:0 (29.6%) and the major ubiquinone was Q-12 (71.1%). It had a guanine-plus-cytosine content of 41.5 mol%. The taxonomic description of Legionella thermalis sp. nov. is proposed to be type strain L-47(T) (JCM 30970(T) = KCTC 42799(T)). PMID- 26865128 TI - Improving procedural performance through warm-up and mental imagery. PMID- 26865129 TI - Limitations of body mass index as an obesity measure of perioperative risk. PMID- 26865127 TI - Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is a fatal disease with rising incidence in the world. For advanced HCC, sorafenib, a multikinase inhibitor, is the only systemic therapy with proven survival benefits. Sorafenib is a pan-VEGF receptor inhibitor, and thus many studies have focused its antivascular effects. But VEGF also acts as an immunosuppressive molecule. VEGF can inhibit maturation of dendritic cells, promote immune suppressive cell infiltration and enhance immune checkpoint molecules expression. On the other hand, potent VEGF inhibition may increase tumor hypoxia, which could hinder antitumor immunity or immunotherapy. Thus, achieving synergy when combining anti-VEGF therapy with immunotherapy may require proper polarization of the tumor microenvironment by dose titration or combination with other immunomodulating agents. PMID- 26865130 TI - Emergence delirium or pain after anaesthesia--how to distinguish between the two in young children: a retrospective analysis of observational studies. AB - BACKGROUND: Early postoperative negative behaviour in preschool children after general anaesthesia is a common problem. The distinction between emergence delirium (ED) and pain is difficult, but management differs between the two. The aim of the current analysis was to identify individual observational variables that can be used to diagnose ED and allow distinction from postoperative pain. METHODS: This retrospective analysis of data from three previous prospective observational studies included children undergoing general anaesthesia for elective adeno-tonsillectomy, sub-umbilical surgery, and MRI scanning. Two trained observers simultaneously applied the Face, Legs, Activity, Cry, Consolability Scale; the Children's Hospital Eastern Ontario Pain Scale; the Children's and Infants' Postoperative Pain Scale or the Paediatric Anaesthesia Emergence Delirium (PAED) scale. Data from each domain of the scales were available at awakening and at five, 10, and 15 min after anaesthesia. Each patient was analysed over time, and subsequently, each evaluation was considered as a single event. The descriptive behaviour items overlapping in the assessed scales were identified as dichotomous variable ('true/false') and then were applied for each evaluation. RESULTS: Children (n=512) were assessed for a total of 2048 evaluations. Most children (69%) displayed at least one episode of ED and/or pain. Almost 15% of children demonstrated both ED and pain. Children with ED showed 'no eye contact' and 'no awareness of surroundings'. Children with pain displayed 'abnormal facial expression', 'crying', and 'inconsolability'. CONCLUSIONS: 'No eye contact' and 'no awareness of surroundings' identifies ED. 'Abnormal facial expression', 'crying', and 'inconsolability' indicate acute pain in children in the early postoperative period. PMID- 26865132 TI - A new method for determining the insertion depth of tracheal tubes in children: a pilot study. AB - BACKGROUND: Choosing the correct insertion depth of tracheal tubes is crucial for successful airway management in paediatrics. Currently used formulas are based on patient characteristics such as age, body weight and height. The aim of the study is to devise and evaluate more suitable body surface area based diagrams for predicting the correct tracheal insertion depth. METHODS: Calculated insertion depth according to currently used formulas, primary insertion depth and insertion depth corrected by chest radiography ('gold standard') were collected from 237 children. Age, body weight, height and body surface area were noted. Body surface area based diagrams were devised and prospectively evaluated in another set of 123 paediatric patients. RESULTS: Tracheal tube position according to currently used formulas had to be corrected in 37% of all intubations. New body surface area based diagrams were created. In 20.3%, depth of the tracheal tube had to be corrected according to the new body surface area based diagrams. CONCLUSIONS: The body surface area based diagrams may be a reliable tool for predicting the correct tracheal insertion depth in children. PMID- 26865131 TI - Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage. AB - BACKGROUND: Dexmedetomidine, a sedative agent, provides neuroprotection when administered during or before brain ischaemia. This study was designed to determine whether dexmedetomidine post-treatment induces neuroprotection against subarachnoid haemorrhage (SAH) and the mechanisms for this effect. METHODS: Subarachnoid haemorrhage was induced by endovascular perforation to the junction of the right middle and anterior cerebral arteries in adult rats. Dexmedetomidine was applied immediately or 2 h after onset of SAH. Neurological outcome was evaluated 2 days after SAH. Right frontal cortex area 1 was harvested 24 h after SAH for western blotting. RESULTS: Subarachnoid haemorrhage reduced neurological scores and increased brain oedema and blood-brain barrier permeability. These effects were attenuated by dexmedetomidine post-treatment. Neuroprotection by dexmedetomidine was abolished by PD98095, an inhibitor of extracellular signal regulated kinase (ERK) activation. Phospho-ERK, the activated form of ERK, was increased by dexmedetomidine; this activation was inhibited by PD98095. CONCLUSIONS: Dexmedetomidine post-treatment provides neuroprotection against SAH. This effect appears to be mediated by ERK. PMID- 26865133 TI - Comparison of tissue distribution, phrenic nerve involvement, and epidural spread in standard- vs low-volume ultrasound-guided interscalene plexus block using contrast magnetic resonance imaging: a randomized, controlled trial. AB - BACKGROUND: Ultrasound guidance allows for the use of much lower volumes of local anaesthetics for nerve blocks, which may be associated with less aberrant spread and fewer complications. This randomized, controlled study used contrast magnetic resonance imaging to view the differential-volume local anaesthetic distribution, and compared analgesic efficacy and respiratory impairment. METHODS: Thirty patients undergoing shoulder surgery were randomized to receive ultrasound-guided interscalene block by a single, blinded operator with injection of ropivacaine 0.75% (either 20 or 5 ml) plus the contrast dye gadopentetate dimeglumine, followed by magnetic resonance imaging. The primary outcome was epidural spread. Secondary outcomes were central non-epidural spread, contralateral epidural spread, spread to the phrenic nerve, spirometry, ultrasound investigation of the diaphragm, block duration, pain scores during the first 24 h, time to first analgesic consumption, and total analgesic consumption. RESULTS: All blocks provided fast onset and adequate intra- and postoperative analgesia, with no significant differences in pain scores at any time point. Epidural spread occurred in two subjects of each group (13.3%); however, spread to the intervertebral foramen and phrenic nerve and extensive i.m. local anaesthetic deposition were significantly more frequent in the 20 ml group. Diaphragmatic paralysis occurred twice as frequently (n=8 vs 4), and changes from baseline peak respiratory flow rate were larger [Delta=-2.66 (1.99 sd) vs -1.69 (2.0 sd) l min( 1)] in the 20 ml group. CONCLUSIONS: This study demonstrates that interscalene block is associated with epidural spread irrespective of injection volume; however, less central (foraminal) and aberrant spread after low-volume injection may be associated with a more favourable risk profile. CLINICAL TRIAL REGISTRATION: This study was registered with the European Medicines Agency (Eudra CT number 2013-004219-36) and with the US National Institutes' of Health registry and results base, clinicaltrials.gov (identifier NCT02175069). PMID- 26865134 TI - Suitability of a preserved human cadaver model for the simulation of facemask ventilation, direct laryngoscopy and tracheal intubation: a laboratory investigation. AB - BACKGROUND: Using fresh or formalin-embalmed cadavers has not been generally accepted for the purposes of teaching airway management. We investigated whether cadavers 'preserved according Thiel's embalming method' (PATEM) are suitable for the simulation of facemask ventilation and tracheal intubation by direct laryngoscopy. METHODS: This observational cluster sampling, controlled simulation study, included eight PATEM cadavers and eight manikins in two clusters. Twenty experienced anaesthetists were randomly assigned to execute 80 facemask ventilations and 80 tracheal intubations in both groups. The ease of facemask ventilation was the primary endpoint. The secondary endpoint was the composite outcomes of laryngoscopy and tracheal intubation. RESULTS: The success rate at the first attempt at mask ventilation was 74% (59/80 attempts) on cadavers and 41% (33/80 attempts) on manikins (P<0.0001). Twenty one subjects received an oral airway in both groups and succeeded in facemask ventilation 20 times on cadavers and four times on manikins (P=0.004). Two-handed technique mask ventilation was required 24 times on manikins and once on cadavers (P=0.0016). In one attempt on a manikin the mask ventilation was impossible. Poor laryngeal view (Cormack Lehane grade 3) occurred 14 times among cadavers (17.5%) and once in manikins (1.25%) (P=0.007), whereas difficulties in tracheal intubation were encountered 16 times in cadavers (20%) vs 17 times in manikins (21.25%) (P=0.84). In a subjective evaluation the participants preferred the cadaver model over the manikins (P<0.0001). CONCLUSIONS: PATEM cadavers were better suited for facemask ventilation and provided a more realistic environment for laryngoscopy and tracheal intubation than the studied manikins. PMID- 26865135 TI - Evidence for nociceptin/orphanin FQ (NOP) but not u (MOP), delta (DOP) or kappa (KOP) opioid receptor mRNA in whole human blood. AB - BACKGROUND: While it is well known that opioids depress the immune system, the site(s) of action for this depression is highly controversial. Immune modulation could occur directly at the immune cell or centrally via the hypothalamic pituitary-adrenal axis. In a number of studies using individual enriched immune cell populations we have failed to detect classical u (MOP), delta (DOP) and kappa (KOP) receptors. The non-classical nociceptin/orphanin FQ (N/OFQ) receptor (NOP) is expressed on all cells examined thus far. Our hypothesis was that immune cells do not express classical opioid receptors and that using whole blood would definitively answer this question. METHODS: Whole blood (containing all immune cell types) was incubated with opioids (morphine and fentanyl) commonly encountered in anaesthesia and with agents mimicking sepsis [lipopolysaccharide (LPS) and peptidoglycan G (PepG)]. Opioid receptor mRNA expression was assessed by endpoint polymerase chain reaction (PCR) with gel visualisation and quantitative PCR. RESULTS: Classical MOP, DOP, and KOP receptors were not detected in any of the samples tested either at rest or when challenged with opioids, LPS or PepG. Commercial primers for DOP did not perform well in quantitative PCR, so the absence of expression was confirmed using a traditional gel-based approach. NOP receptors were detected in all samples; expression was unaffected by opioids and reduced by LPS/PepG combinations. CONCLUSIONS: Classical opioid receptors are not expressed on circulating immune cells. PMID- 26865136 TI - Limits of agreement may have large confidence intervals. PMID- 26865137 TI - Schneider regimen vs a volatile inhalation anaesthetic (desflurane) for laparoscopic adrenalectomy and additional considerations for delivery of anaesthesia. PMID- 26865138 TI - Reply from the authors. Schneider regimen vs a volatile inhalation anaesthetic (desflurane) for laparoscopic adrenalectomy and additional considerations for delivery of anaesthesia. PMID- 26865139 TI - Is one acceleromyographically measured train-of-four ratio sufficient after sugammadex to identify residual curarization in postoperative, awake patients? PMID- 26865140 TI - Sugammadex and residual neuromuscular block: what is acceptable normal practice? PMID- 26865141 TI - Hidden universality of residual neuromuscular block. PMID- 26865142 TI - Managing malaria in the intensive care unit. PMID- 26865143 TI - Salt at fault? PMID- 26865144 TI - Intraoperative ventilation: improving physiology, or preventing harm? PMID- 26865145 TI - Reply from the authors. Individualized ventilatory strategy: ameliorate lung injury while preserving physiology. PMID- 26865152 TI - Anesthesia Exposure and Risk of Dementia and Alzheimer's Disease: A Prospective Study. AB - OBJECTIVES: To evaluate the associations between anesthesia and dementia or Alzheimer's disease (AD) risk using prospectively collected data. DESIGN: Cohort study. PARTICIPANTS: Community-dwelling members of the Adult Changes in Thought cohort aged 65 and older and free of dementia at baseline (N = 3,988). MEASUREMENTS: Participants self-reported all prior surgical procedures with general or neuraxial (spinal or epidural) anesthesia at baseline and reported new procedures every 2 years. People undergoing high-risk surgery with general anesthesia, other surgery with general anesthesia, and other surgery with neuraxial anesthesia exposures were compared with those with no surgery and no anesthesia. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia and AD associated with time varying lifetime and recent (past 5 years) anesthesia exposures. RESULTS: At baseline, 254 (6%) people reported never having anesthesia; 248 (6%) had had one or more high-risk surgeries with general anesthesia, 3,363 (84%) had had one or more other surgeries with general anesthesia, and 123 (3%) had had one or more surgeries with neuraxial anesthesia. High-risk surgery with general anesthesia was not associated with greater risk of dementia (HR = 0.86, 95% CI = 0.58-1.28) or AD (HR = 0.95, 95% CI = 0.61-1.49) than no history of anesthesia. People with any history of other surgery with general anesthesia had a lower risk of dementia (HR = 0.63, 95% CI = 0.46-0.85) and AD (HR = 0.65, 95% CI = 0.46-0.93) than people with no history of anesthesia. There was no association between recent anesthesia exposure and dementia or AD. CONCLUSION: Anesthesia exposure was not associated with of dementia or AD in older adults. PMID- 26865153 TI - Glycosylated haemoglobin assessment in diabetic patients with acute coronary syndromes. AB - BACKGROUND: Guidelines for the management of acute coronary syndromes (ACS) advocate for maintaining adequate long-term glycaemic control in diabetic patients. Glycosylated haemoglobin (HbA1c) measurement is commonly used to monitor long-term glycaemic control in diabetes. AIMS: To evaluate the frequency and clinical predictors of in-hospital HbA1c measurement in diabetic patients presenting with ACS and the relationship between HbA1c assessment and mortality following discharge. METHODS: This registry-based cohort study included 1743 diabetic patients from 33 representative hospitals across Australia with a final diagnosis of ACS. Independent predictors of HbA1c assessment were evaluated using a multivariable logistic generalised estimating equations analysis. The association between HbA1c assessment and mortality following discharge was evaluated using Cox proportional hazard analysis. RESULTS: Seven hundred and fourteen (41%) patients had HbA1c assessment during admission. Frequency of assessment varied markedly between hospitals (7.7-87.6%). HbA1c assessment was significantly more frequent in hospitals with catheterisation laboratories. Frequency of assessment was not associated with location of hospital (rural vs urban) or hospital capacity. Independent clinical predictors of HbA1c assessment across participating hospitals were younger age, ST-Elevation Myocardial Infarction, cardiac catheterisation and coronary artery bypass surgery during admission. HbA1c assessment was associated with higher rates of coronary catheterisation, revascularisation and receipt of evidence-based medicines but not with mortality during 6 months following discharge (hazard ratio, 0.48; 95% confidence interval, 0.19-1.18). CONCLUSION: Frequency of HbA1c assessment varies markedly between hospitals, and most diabetic patients admitted for ACS in Australia do not receive assessment of pre-admission glycaemic control. HbA1c assessment was associated with better evidence driven medical care. PMID- 26865154 TI - A comparison between the MoCA and the MMSE visuoexecutive sub-tests in detecting abnormalities in TIA/stroke patients. AB - BACKGROUND: Executive dysfunction predicts stroke risk, dementia, and mortality. The Montreal cognitive assessment detects more visuoexecutive dysfunction than the mini-mental state examination but it is unclear which of the individual Montreal cognitive assessment visuoexecutive items contribute to the better performance of the Montreal cognitive assessment. We therefore determined the relative performance of the Montreal cognitive assessment visuoexecutive sub tests versus the mini-mental state examination pentagon copying in patients with stroke and transient ischemic attack. METHODS: Mini-mental state examination and Montreal cognitive assessment were administered to a prospective, population based cohort of stroke, and transient ischemic attack patients from the Oxford Vascular Study at six month or five-year follow-up between November 2007 and June 2009. We compared the proportion of participants with incorrect Montreal cognitive assessment visuoexecutive tasks and sub-tasks but correct mini-mental state examination pentagon copying versus the proportion with incorrect MMSE pentagon copying but correct visuoexecutive Montreal cognitive assessment sub test and individual sub-test items. RESULTS: Among 412 patients assessed with the mini-mental state examination and Montreal cognitive assessment, the Montreal cognitive assessment detected more visuoexecutive dysfunction than the mini mental state examination (OR 11.4, 95% CI 8.2-15.8, p < 0.001). The likelihood of incorrect mini-mental state examination pentagon copying increased as the numbers of correct MoCA visuoexecutive responses decreased: 2/106 (1.9%) and 9/10 (90.0%) incorrect mini-mental state examination pentagon copying for 5/5 and 0/5 correct Montreal cognitive assessment visuoexecutive tasks, respectively (p for trend 0.005). Each Montreal cognitive assessment visuoexecutive sub-task, including trails (39.6%), cube copying (49.5%), and clock drawing (59.0%), detected more patients with visuoexecutive dysfunction than the mini-mental state examination pentagon copying (20.6%, p < 0.001). CONCLUSION: All three of the Montreal cognitive assessment visuoexecutive sub-tests detected more abnormalities than the mini-mental state examination pentagon copying and thus contributed to the over 10-fold superiority of Montreal cognitive assessment over the mini-mental state examination for detection of visuoexecutive dysfunction. PMID- 26865155 TI - Pre-hospital delays in ischemic stroke patients in a Malaysian tertiary hospital. PMID- 26865156 TI - Introducing @microbleeds: A pilot Twitter space for cerebral microbleeds research. PMID- 26865157 TI - Epidemiology of ischemic strokes in elderly. PMID- 26865158 TI - Research ethics committees in the regulation of clinical research: comparison of Finland to England, Canada, and the United States. AB - BACKGROUND: The aim of this paper is to compare common features and variation in the work of research ethics committees (RECs) in Finland to three other countries - England, Canada, the United States of America (USA) - in the late 2000s. METHODS: Several approaches and data sources were used, including semi- or unstructured interviews of experts, documents, previous reports, presentations in meetings and observations. A theoretical framework was created and data from various sources synthesized. RESULTS: In Finland, RECs were regulated by a medical research law, whereas in the other countries many related laws and rules guided RECs; drug trials had specific additional rules. In England and the USA, there was a REC control body. In all countries, members were voluntary and included lay-persons, and payment arrangements varied. Patient protection was the main ethics criteria, but other criteria (research advancement, availability of results, payments, detailed fulfilment of legislation) varied. In all countries, RECs had been given administrative duties. Variations by country included the mandate, practical arrangements, handling of multi-site research, explicitness of proportionate handlings, judging scientific quality, time-limits for decisions, following of projects, role in institute protection, handling conflicts of interests, handling of projects without informed consent, and quality assurance research. The division of work between REC members and secretariats varied in checking of formalities. In England, quality assurance of REC work was thorough, fairly thorough in the USA, and not performed in Finland. CONCLUSIONS: The work of RECs in the four countries varied notably. Various deficiencies in the system require action, for which international comparison can provide useful insights. PMID- 26865159 TI - Phenotypic and Neuropathological Characterization of Fetal Pyruvate Dehydrogenase Deficiency. AB - To distinguish pyruvate dehydrogenase deficiency (PDH) from other antenatal neurometabolic disorders thereby improving prenatal diagnosis, we describe imaging findings, clinical phenotype, and brain lesions in fetuses from 3 families with molecular characterization of this condition. Neuropathological analysis was performed in 4 autopsy cases from 3 unrelated families with subsequent biochemical and molecular confirmation of PDH complex deficiency. In 2 families there were mutations in the PDHA1 gene; in the third family there was a mutation in the PDHB gene. All fetuses displayed characteristic craniofacial dysmorphism of varying severity, absence of visceral lesions, and associated encephaloclastic and developmental supra- and infratentorial lesions. Neurodevelopmental abnormalities included microcephaly, migration abnormalities (pachygyria, polymicrogyria, periventricular nodular heterotopias), and cerebellar and brainstem hypoplasia with hypoplastic dentate nuclei and pyramidal tracts. Associated clastic lesions included asymmetric leukomalacia, reactive gliosis, large pseudocysts of germinolysis, and basal ganglia calcifications. The diagnosis of PDH deficiency should be suspected antenatally with the presence of clastic and neurodevelopmental lesions and a relatively characteristic craniofacial dysmorphism. Postmortem examination is essential for excluding other closely related entities, thereby allowing for biochemical and molecular confirmation. PMID- 26865160 TI - High-mobility capacitively-induced two-dimensional electrons in a lateral superlattice potential. AB - In the presence of a lateral periodic potential modulation, two-dimensional electrons may exhibit interesting phenomena, such as a graphene-like energy momentum dispersion, Bloch oscillations, or the Hofstadter butterfly band structure. To create a sufficiently strong potential modulation using conventional semiconductor heterostructures, aggressive device processing is often required, unfortunately resulting in strong disorder that masks the sought after effects. Here, we report a novel fabrication process flow for imposing a strong lateral potential modulation onto a capacitively induced two-dimensional electron system, while preserving the host material quality. Using this process flow, the electron density in a patterned Si/SiGe heterostructure can be tuned over a wide range, from 4.4 * 10(10) cm(-2) to 1.8 * 10(11) cm(-2), with a peak mobility of 6.4 * 10(5) cm(2)/V.s. The wide density tunability and high electron mobility allow us to observe sequential emergence of commensurability oscillations as the density, the mobility, and in turn the mean free path, increase. Magnetic-field-periodic quantum oscillations associated with various closed orbits also emerge sequentially with increasing density. We show that, from the density dependence of the quantum oscillations, one can directly extract the steepness of the imposed superlattice potential. This result is then compared to a conventional lateral superlattice model potential. PMID- 26865161 TI - Capecitabine in the routine first-line treatment of elderly patients with advanced colorectal cancer--results from a non-interventional observation study. AB - BACKGROUND: The purpose of this observational study was to evaluate feasibility, efficacy results and toxicity observations of capecitabine in routine first line treatment of patients with metastatic colorectal cancer, with particular regard of elderly patients (>75 years of age). METHODS: Patients with colorectal cancer receiving capecitabine as part of their first-line treatment were recorded until detection of disease progression or up to a maximum of 12 cycles on standardized evaluation forms. Additional information on long-term outcomes, progression-free survival, and overall survival were retrieved at two follow-up time points. Obtained data were analyzed with regard to age up to 75 and >75 years of age. There were no specific requirements for patient selection and conduct of therapy, corresponding to the non-interventional nature of the study. RESULTS: In total, 1249 evaluable patients were enrolled in Germany. The median age of the study population was 74 years (range: 21-99). Capecitabine-based combination was administered in 56% of patients in the overall population. The median treatment duration was about 5 months. Severe toxicities occurred rarely without any difference regarding age groups. The most common hematological toxicity was anemia. Gastrointestinal side effects and hand-food-syndrome (HFS) were the most frequent non-hematologic toxicities. Overall response rate (ORR) was significantly higher in the patient group <=75 years compared to patients >75 years of age (38 vs. 32%, p=0.019). Median progression free survival (PFS 9.7 vs. 8.2 months, p=0.00021) and overall survival (OS 31.0 vs. 22.6 months, p<0.0001) was decreased in elderly patients. CONCLUSION: Efficacy and tolerability of capecitabine treatment either as single drug or in various combination regimens, as proven in randomized studies, could be confirmed in a clinical routine setting. Patients older than 75 years may derive a relevant benefit by first line capecitabine-based treatment with good tolerability. PMID- 26865162 TI - Acceptance and commitment therapy for adults with advanced cancer (CanACT): study protocol for a feasibility randomised controlled trial. AB - BACKGROUND: One-third of people with cancer experience psychological distress and may suppress distressing thoughts, emotions, and concerns, leading to further problems. Conventional psychological treatments reduce distress by problem solving, but in advanced cancer, when ill health is progressive and death may be approaching, physical and psychological difficulties are complex and have no simple solutions. Acceptance and Commitment Therapy encourages acknowledgement and acceptance of mental experiences, increasing people's ability to work with problems that cannot be solved. Previous pilot work in advanced cancer confirms that distress can be associated with an avoidance of experiencing uncomfortable thoughts and emotions. METHODS/DESIGN: This feasibility randomised controlled trial of Acceptance Commitment Therapy aims to establish parameters for a larger trial. Fifty-four participants with advanced cancer will be randomly allocated to up to eight sessions (each 1 hour) of Acceptance Commitment Therapy or a talking control. Participants will be recruited from those attending outpatient services and hospice day care at three specialist palliative care units in North and East London, United Kingdom. The primary outcome is a measure of functioning in four areas of life (physical, social/family, emotional, and general activity) using the Functional Assessment of Cancer Therapies--General questionnaire at 3 months after randomisation. Secondary outcomes are (i) acceptance using the Acceptance and Action Questionnaire; (ii) psychological distress using the Kessler Psychological Distress Scale; (iii) physical functioning using a timed walk and sit-to-stand test; and (iv) quality of life measures including the Euroqol-5 Dimensions and ICECAP Supportive Care measures. Qualitative data will be collected at 3 months to explore the participants' experiences of the trial and therapy. Data will be collected on the costs of care. DISCUSSION: Data generated on the recruitment, retention, and experience of the interventions and the usefulness of the outcome measures will inform the adaptations required and whether changes in function are consistent with existing data when planning for a sufficiently powered randomised controlled trial. TRIAL REGISTRATION: ISRCTN13841211 (registered 22 July 2015). PMID- 26865163 TI - Hepatitis C virus NS3-4A inhibits the peroxisomal MAVS-dependent antiviral signalling response. AB - Hepatitis C virus (HCV) is the cause of one of the most prevalent viral infections worldwide. Upon infection, the HCV genome activates the RIG-I-MAVS signalling pathway leading to the production of direct antiviral effectors which prevent important steps in viral propagation. MAVS localizes at peroxisomes and mitochondria and coordinate the activation of an effective antiviral response: peroxisomal MAVS is responsible for a rapid but short-termed antiviral response, while the mitochondrial MAVS is associated with the activation of a stable response with delayed kinetics. The HCV NS3-4A protease was shown to specifically cleave the mitochondrial MAVS, inhibiting the downstream response. In this study, we have analysed whether HCV NS3-4A is also able to cleave the peroxisomal MAVS and whether this would have any effect on the cellular antiviral response. We show that NS3-4A is indeed able to specifically cleave this protein and release it into the cytosol, a mechanism that seems to occur at a similar kinetic rate as the cleavage of the mitochondrial MAVS. Under these conditions, RIG-I-like receptor (RLR) signalling from peroxisomes is blocked and antiviral gene expression is inhibited. Our results also show that NS3-4A is able to localize at peroxisomes in the absence of MAVS. However, mutation studies have shown that this localization pattern is preferred in the presence of a fully cleavable MAVS. These findings present evidence of a viral evasion strategy that disrupts RLR signalling on peroxisomes and provide an excellent example of how a single viral evasion strategy can block innate immune signalling from different organelles. PMID- 26865166 TI - Does the development of chronic kidney disease and acute kidney injury affect the prognosis after living donor liver transplantation? AB - BACKGROUND AND AIMS: Chronic kidney disease (CKD) and acute kidney injury (AKI) have been discussed as complications following living donor liver transplantation (LDLT). The aim of this study was to clarify the relationships among CKD, AKI, and the prognosis after LDLT. METHODS: This study included 118 patients who underwent LDLT in our department. A low eGFR (<60 mL/min/1.73 m(2) ) was regarded to indicate CKD. AKI 1 and AKI 2 were characterized by an increase in the serum creatinine level of 0.5 and 1.0 mg/dL, respectively, within one wk after LDLT. We investigated the risk factors for and the relevance of CKD and AKI on the prognosis. RESULTS: AKI 1 was associated with sepsis and intra-operative bleeding (p = 0.0032, p = 0.001). AKI 2 was associated with sepsis and hepatitis C infection (p < 0.001, p = 0.027). A pre-operative eGFR of 60-89 and diabetes were the risk factors for the development of CKD in POY 2 (p = 0.018, p = 0.002). AKI 2, sepsis, and diabetes were the risk factors for the patient death within one yr after LDLT (p = 0.010, p = 0.002, p = 0.022). AKI 2 and sepsis were the risk factors for death within two yr after LDLT (p = 0.005, p = 0.018). CONCLUSIONS: Recognizing the risk factors and careful management for preventing both AKI and CKD may improve the prognosis of patients following LDLT. PMID- 26865164 TI - tRNA-Derived Small Non-Coding RNAs in Response to Ischemia Inhibit Angiogenesis. AB - Ischemic injuries will lead to necrotic tissue damage, and post-ischemia angiogenesis plays critical roles in blood flow restoration and tissue recovery. Recently, several types of small RNAs have been reported to be involved in this process. In this study, we first generated a rat brain ischemic model to investigate the involvement of new types of small RNAs in ischemia. We utilized deep sequencing and bioinformatics analyses to demonstrate that the level of small RNA fragments derived from tRNAs strikingly increased in the ischemic rat brain. Among these sequences, tRNA(Val)- and tRNA(Gly)-derived small RNAs account for the most abundant segments. The up-regulation of tRNA(Val)- and tRNA(Gly) derived fragments was verified through northern blot and quantitative PCR analyses. The levels of these two fragments also increased in a mouse hindlimb ischemia model and cellular hypoxia model. Importantly, up-regulation of the tRNA(Val)- and tRNA(Gly)-derived fragments in endothelial cells inhibited cell proliferation, migration and tube formation. Furthermore, we showed that these small RNAs are generated by angiogenin cleavage. Our results indicate that tRNA derived fragments are involved in tissue ischemia, and we demonstrate for the first time that tRNA(Val)- and tRNA(Gly)-derived fragments inhibit angiogenesis by modulating the function of endothelial cells. PMID- 26865167 TI - Continuous Renal Replacement Therapy in NICU - Indian Experience. PMID- 26865168 TI - Application of Flow Cytometry in the Evaluation of Primary Immunodeficiencies. AB - Primary immunodeficiency disorders (PIDDs) are a heterogeneous group of inherited disorders of the immune system. Currently more than 250 different PIDDs with a known genetic defect have been recognized. The diagnosis of many of these disorders is supported strongly by a wide variety of flow cytometry applications. Flow cytometry offers a rapid and sensitive tool for diagnosis and classification of PIDDs. It is applicable in the initial workup and subsequent management of several primary immunodeficiency diseases. As our understanding of the pathogenesis and management of these diseases increases, the majority of these tests can be easily established in the diagnostic laboratory. Thus, the focus of this article is on the application of flow cytometry in the diagnosis and/or evaluation of PIDDs. PMID- 26865169 TI - Nutritional Status of Rural Bengali Adolescent Boys of Tripura: Author's Reply. PMID- 26865170 TI - Disseminated Intravascular Coagulation in Ulcerative Colitis. PMID- 26865171 TI - Nutritional Status of Rural Bengali Adolescent Boys of Tripura: Correspondence. PMID- 26865172 TI - Chronic Granulomatous Disease. AB - Chronic granulomatous disease (CGD) is the most common symptomatic phagocytic defect. It is caused by mutations in genes encoding protein subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD is characterized by a defective intracellular killing of phagocytosed organisms due to a defective oxidative burst in the neutrophils and macrophages. It is inherited in either X-linked recessive or autosomal recessive pattern. Staphylococcus aureus and Aspergillus species are the most common organisms reported. Infections with Burkholderia, Serratia, and Nocardia warrant a screen for CGD. Suppurative lymphadenitis, cutaneous abscesses, pneumonia and diarrhea constitute the most common problems in children with CGD. A small percentage of children develop autoimmune manifestations (e.g., rheumatoid arthritis, systemic lupus erythematosus, colitis, autoimmune hepatitis) and warrant immunosuppression. X-linked carriers of CGD are at an increased risk of developing autoimmune diseases. Nitroblue-tetrazolium dye reduction test and dihydro-rhodamine assay by flow cytometry are the screening tests for this disorder. While most children do well on long term antibiotic and antifungal prophylaxis, those with severe forms warrant hematopoietic stem cell transplant. The role of regular interferon-gamma injections is debatable. Evidence for white cell transfusions is sparse, and gene therapy is under trial.This current review highlights various aspects and studies in CGD. X-linked form of CGD has been noted to carry a poorer prognosis compared to autosomal recessive variants. However, recent evidence suggests that outcome in CGD is determined by the amount of residual NADPH oxidase activity irrespective of mode of inheritance. PMID- 26865173 TI - Psychometric properties of the Positive Mental Health Scale (PMH-scale). AB - BACKGROUND: In recent years, it has been increasingly recognized that the absence of mental disorder is not the same as the presence of positive mental health (PMH). With the PMH-scale we propose a short, unidimensional scale for the assessment of positive mental health. The scale consists of 9 Likert-type items. METHODS: The psychometric properties of the PMH-scale were tested in a series of six studies using samples from student (n = 5406), patient (n = 1547) and general (n = 3204) populations. Factorial structure and measurement equivalence were tested with the measurement invariance testing. The factor models were analysed with the maximum likelihood procedure. Internal consistency was examined using Cronbach's alpha, test-retest reliability, convergent and divergent validity was examined by Pearson correlation. Sensitivity to (therapeutic) change was examined with the t-test. RESULTS: Results confirmed unidimensionality, scalar invariance across samples and over time, high internal consistency, good retest-reliability, good convergent and discriminant validity as well as sensitivity to therapeutic change. CONCLUSIONS: These findings suggest that the PMH-Scale indeed measures a single concept and allows us to compare scores over groups and over time. The PMH scale thus is a brief and easy to interpret instrument for measuring PMH across a large variety of relevant groups. PMID- 26865174 TI - Racial disparities in esophageal cancer survival after surgery. AB - OBJECTIVES: Esophageal cancer (EC) black patients have higher mortality rates than Whites. The lower rate of surgery in Blacks may explain the survival difference. We explored the Surveillance Epidemiology and End Results database to determine the impact of surgery on mortality in Blacks and Whites EC. METHODS: All cases of pathologically proven local and locoregional adenocarcinoma and squamous cell carcinoma of the esophagus from 1973 to 2011 were identified (13,678 White, 2,894 Black patients). Cervical esophageal cancer was excluded. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race. RESULTS: Blacks had higher 1-year mortality, adjusted for age, sex, stage, year of diagnosis, histology, and therapy [adjusted hazard ratio (HRadj ): 1.24 (95% CI 1.16-1.32)]. Undergoing surgery was an independent predictor of improved survival overall (HRadj 0.30, 95% CI 0.27-0.33). Black patients treated surgically experienced significantly lower survival than Whites, but the difference was not observed in those who did not undergo surgery. CONCLUSIONS: Although surgery appears to reduce mortality overall, early survival is worse for Blacks. Investigation into racial disparities in health care access and delivery, and to skilled esophageal surgeons is warranted to improve survival for all patients, particularly Blacks. J. Surg. Oncol. 2016;113:659-664. (c) 2016 Wiley Periodicals, Inc. PMID- 26865175 TI - Controlled wettability based on reversible micro-cracking on a shape memory polymer surface. AB - Wettability modification on a polymer surface is of immense importance for flexible electronics and biomedical applications. Herein, controlled wettability of a styrene-based shape memory polymer has been realized by introducing micro cracks on the polymer surface for the first time. The cracks were purposely prepared by thin metal film constrained deformation on the polymer. After the removal of the metallic film, wettability was dramatically enhanced by showing a remarkable reduction in the contact angle with water droplets from 85 degrees to 25 degrees . Subsequent systematic characterization techniques like XPS and SEM revealed that such observation could be attributed to the increased density of hydrophilic groups and the roughened surface. In addition, by controlling the temperature for annealing the treated polymer, the surface could be switched reversely to water-repellent. Therefore, this paper offers a smart tactic to manipulate the surface wettability of a shape memory polymer freely. The features of the controlled wettability surface such as high tenability, high stability and easy fabrication are promising for microfluidic switching and molecule/cell capture-release. PMID- 26865176 TI - Alkaloids from Oxytropis ochrocephala and antiproliferative activity of sophoridine derivatives against cancer cell lines. AB - Ten alkaloids (1-10), with sophoridine (1) as the most abundant component, were obtained from the whole plants of Oxytropis ochrocephala Bunge. Furthermore, eight new sophoridine derivatives (11-16, 20, 21), with modification on the C-14 position of 1 were synthesized. All compounds (1-16, 20, 21) were evaluated for antiproliferative activity against five human tumor cell lines. Among them, the newly synthesized derivative 20 exhibited the best inhibitory activity against the tested cell lines. Its activity was increased by more than fourfold as compared with parent compound 1. PMID- 26865178 TI - Eculizumab for the treatment of atypical hemolytic uremic syndrome recurrence after kidney transplantation associated with complement factor H mutations: a case report with a 5-year follow-up. PMID- 26865177 TI - FGF-23 levels are associated with vascular calcification, but not with atherosclerosis, in hemodialysis patients. AB - PURPOSE: High fibroblast growth factor-23 (FGF-23) levels are associated with mortality and cardiovascular events in patients with chronic kidney disease. The aim of this cross-sectional study was to investigate the relationship between plasma FGF-23 levels and coronary artery calcification and carotid artery intima media thickness (CA-IMT) in hemodialysis (HD) patients. METHODS: In this cross sectional study, plasma intact FGF-23 levels were measured in 229 patients who underwent coronary artery calcification scores (CACs) determined by multi-slice computerized tomography and CA-IMT assessed by using high-resolution color Doppler ultrasonography. RESULTS: Median FGF-23 was 53.5 pg/ml (IQR 30.8-249.5). Median CACs was 98 (IQR 0-531), and the frequency of patients with severe calcification (CACs > 400) was 28.8%; 27.5% of cases had no calcification. Mean CA-IMT was 0.78 +/- 0.20 mm, and the presence of carotid plaques was 51% with a mean length 2.1 mm. FGF-23 level was positively correlated with serum calcium (r = 0.337, p < 0.001), phosphate (r = 0.397, p < 0.001) and CACs (r = 0.218, p = 0.001). Neither CA-IMT nor the presence of carotid artery plaques correlated with FGF-23 levels. In adjusted ordinal regression analysis, FGF-23 level was an independent predictor for severe CACs together with age, gender, presence of diabetes, time on dialysis and CA-IMT (model r(2) = 0.44, p < 0.001). As a novel finding, the mean CACs was markedly higher in patients with FGF-23 level above median regardless of phosphate levels (p = 0.03). CONCLUSIONS: In HD patients, plasma FGF-23 level is superior to phosphate in the prediction of coronary artery calcification. However, FGF-23 is not associated with carotid artery atherosclerosis in HD patients. PMID- 26865180 TI - Sex effect on insulin secretion and mitochondrial function in pancreatic beta cells of elderly Wistar rats. AB - AIMS/HYPOTHESIS: Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes in the elderly people. Previous studies have reported the sex differences in risk for type 2 diabetes, especially in the elderly people, whereas reasons for these sex differences remain poorly understood. This study aims to evaluate the effect of sex on glucose-stimulated insulin secretion and mitochondrial function in pancreatic beta cells of Wistar rats. METHODS: 3-month-old and 18-month-old Wistar rats of both sexes were used. Insulin secretion of islets was analyzed by glucose-stimulated insulin secretion and islet perifusion assays; ATP content and oxygen consumption rate of islets were determined to evaluate the mitochondrial function. RESULTS: Insulin secretion of islets under high glucose conditions declined significantly with age in both sexes. Glucose-stimulated insulin secretion of elderly female groups was markedly higher than that of male groups under high glucose conditions. Importantly, islets from elderly female groups showed higher mitochondrial function compared with male counterparts, evidenced by higher ATP content and oxygen consumption rate under high glucose conditions. It was also noted that mitochondrial biogenesis of islets from elderly female rats was significant higher compared with male rats. There were notable increases in expression of genes involved in mitochondrial biogenesis in islets from elderly female rats compared with male rats. CONCLUSION: This study demonstrates a sex dimorphism in the age-associated impairment of pancreatic beta cell function in elderly rats, while the potential mechanism may be related to the sexual differences in mitochondrial biogenesis and function. PMID- 26865181 TI - Supramolecular aggregation of Ni(salen) with (C6F5)2Hg and [o-C6F4Hg]3. AB - As part of our ongoing interest in the supramolecular chemistry of fluorinated organomercurials, we have investigated the interaction of bis(pentafluorophenyl)mercury ((C6F5)2Hg), and trimeric (perfluoro-o phenylene)mercury ([o-C6F4Hg]3), with nickel(II) N,N' bis(salicylidene)ethylenediamine) (Ni(salen)). While solution studies monitored by UV-VIS spectroscopy suggest that Ni(salen) interacts with the trinuclear mercury complex in solution, the 1 : 1 adduct (Ni(salen)-(C6F5)2Hg) and the 1 : 1 adducts Ni(salen)-[o-C6F4Hg]3 and [Ni(salen)-[o-C6F4Hg]3-THF-H2O] can be obtained by slow evaporation of solutions containing the two building blocks. While arene fluoroarene and hydrogen bonding interactions, as well as interactions between mercury and the salen ligand are the predominant forces responsible for the formation of these adducts, Ni(salen)-[o-C6F4Hg]3 and [Ni(salen)-[o-C6F4Hg]3-THF H2O] also display short Ni-Hg separations consistent with the presence of metallophilic interactions. Quantum theory of atoms in molecules (QTAIM) analyses of the Ni-Hg interactions in these adducts finds that these interactions are dominated by electrostatic and dispersion forces, despite featuring non negligible covalent contributions. PMID- 26865179 TI - Artesunate attenuates unilateral ureteral obstruction-induced renal fibrosis by regulating the expressions of bone morphogenetic protein-7 and uterine sensitization-associated gene-1 in rats. AB - PURPOSE: Kidney fibrosis is the most common final stage of progressive renal disease. Bone morphogenetic protein-7 (BMP-7) has been shown to be important in both preservation of kidney function and resistance to injury. Recently, it has been realized that uterine sensitization-associated gene-1 (USAG-1) functions as a kidney-specific BMP antagonist. Because of the reported anti-fibrotic effects of artesunate (Art), this study was designed to investigate the effects of Art on renal fibrosis in unilateral ureteral obstruction (UUO) rats and to explore the underlying mechanisms. METHODS: Thirty male Sprague-Dawley rats were randomly divided into five groups: Sham group, UUO group, low-dose Art-treated (Art-L), middle-dose Art-treated (Art-M), and high-dose Art-treated (Art-H) groups. The UUO rat model was established by ligating the left ureter. Fourteen days later, interstitial collagen deposition, expression of USAG-1, BMP-7, E-cadherin, alpha smooth muscle actin (alpha-SMA), fibronectin (FN), collagen I, as well as the inflammatory infiltration levels in the kidneys were assessed. RESULTS: Art treatment significantly attenuated the deposition of interstitial collagens in the UUO rats' kidneys and exhibited the ability to improve renal function, followed by the up-regulated expression of BMP-7 and E-cadherin and the down regulated expression of USAG-1 and alpha-SMA. In addition, increased macrophages infiltration in the kidneys of the UUO rats were also attenuated by the administration of Art. CONCLUSIONS: These results indicate that Art is able to improve the renal function decline and renal fibrosis induced by UUO, which may be associated with the up-regulation of BMP-7 and down-regulation of USAG-1. Accordingly, Art may become a potential preventive or therapeutic agent for chronic kidney diseases. PMID- 26865183 TI - The Pharmacology of Indomethacin. AB - BACKGROUND: Over 50 years ago, indomethacin emerged as an extremely potent non steroidal anti-inflammatory drug (NSAID) during a massive effort to find effective anti-inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as "indomethacin-responsive" headache disorders. Potential pharmacokinetic and bio-mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation. METHODS/RESULTS: The present article summarizes pharmacologic properties of indomethacin, including pharmacokinetics with particular attention to its distribution into the central nervous system, adverse effects, drug interactions, and mechanisms of action. Data are emphasized where differences in biomechanisms are found between indomethacin and other NSAIDs. The use of indomethacin in pregnant and lactating women is reviewed. CONCLUSIONS: NSAIDs easily enter the brain, but their high protein binding limits absolute amount of entry. All work similarly as either nonselective or selective cyclooxygenase inhibitors, but indomethacin may have more potent vasoconstrictive activity and unique direct neuronal or nitric oxide-dependent inhibitory pathway activity. PMID- 26865182 TI - Calcium and Magnesium Ions Are Membrane-Active against Stationary-Phase Staphylococcus aureus with High Specificity. AB - Staphylococcus aureus (S. aureus) is notorious for its ability to acquire antibiotic-resistance, and antibiotic-resistant S. aureus has become a wide spread cause of high mortality rate. Novel antimicrobials capable of eradicating S. aureus cells including antibiotic-resistant ones are thus highly desired. Membrane-active bactericides and species-specific antimicrobials are two promising sources of novel anti-infective agents for fighting against bacterial antibiotic-resistance. We herein show that Ca(2+) and Mg(2+), two alkaline-earth metal ions physiologically essential for diverse living organisms, both disrupt model S. aureus membranes and kill stationary-phase S. aureus cells, indicative of membrane-activity. In contrast to S. aureus, Escherichia coli and Bacillus subtilis exhibit unaffected survival after similar treatment with these two cations, indicative of species-specific activity against S. aureus. Moreover, neither Ca(2+) nor Mg(2+) lyses mouse red blood cells, indicative of hemo compatibility. This works suggests that Ca(2+) and Mg(2+) may have implications in targeted eradication of S. aureus pathogen including the antibiotic-resistant ones. PMID- 26865184 TI - Lgr5 Marks Neural Crest Derived Multipotent Oral Stromal Stem Cells. AB - It has been suggested that multipotent stem cells with neural crest (NC) origin persist into adulthood in oral mucosa. However their exact localization and role in normal homeostasis is unknown. In this study, we discovered that Lgr5 is expressed in NC cells during embryonic development, which give rise to the dormant stem cells in the adult tongue and oral mucosa. Those Lgr5 positive oral stromal stem cells display properties of NC stem cells including clonal growth and multipotent differentiation. RNA sequencing revealed that adult Lgr5+ oral stromal stem cells express high number of neural crest related markers like Sox9, Twist1, Snai1, Myc, Ets1, Crabp1, Epha2, and Itgb1. Using lineage-tracing experiments, we show that these cells persist more than a year in the ventral tongue and some areas of the oral mucosa and give rise to stromal progeny. In vivo transplantation demonstrated that these cells reconstitute the stroma. Our studies show for the first time that Lgr5 is expressed in the NC cells at embryonic day 9.5 (E9.5) and is maintained during embryonic development and postnataly in the stroma of the ventral tongue, and some areas of the oral mucosa and that Lgr5+ cells participate in the maintenance of the stroma. PMID- 26865185 TI - Three-dimensional ultrasonographic depiction of fetal brain blood vessels. AB - OBJECTIVE: The objective of this study is to evaluate the fetal cerebral vasculature by three-dimensional (3D) ultrasonography and Doppler technologies in normal fetuses and to describe a systematic method for analysis of volume data sets. METHODS: 3D volumes of the fetal brain were acquired prospectively in 25 patients between 12.3 and 36.3 weeks' gestation. Volumes were acquired with high definition Doppler flow. The feasibility of identifying the fetal cerebral blood vessels and venous sinuses was analyzed. RESULTS: A step-by-step systematic approach to identify the cerebral vasculature from ultrasonographic volume data sets was developed. The volumes were rotated into a standard anatomic orientation in the multiplanar display, and then, by systematic navigation, the vessels were demonstrated. Arteries of the circle of Willis, basilar artery, pericallosal artery, and internal carotid arteries were demonstrated in more than half of the fetuses. Tiny vessels such as those that supply the cerebellum and those that branch from the pericallosal artery were demonstrated in less than 50% of the volumes. CONCLUSIONS: The essential fetal cerebral vessels can be visualized by 3D volume analysis. Systematic analysis enables identification of the fetal brain arteries, veins, and sinuses and provides knowledge about anatomical variations and the diversity of human anatomy. (c) 2016 John Wiley & Sons, Ltd. PMID- 26865187 TI - Patients in trials of antidepressants are not typical of those in everyday practice. PMID- 26865186 TI - Profile of retigabine-induced neuronal apoptosis in the developing rat brain. AB - OBJECTIVE: Acute neonatal exposure to some, but not all, anticonvulsant drugs induces a profound increase in neuronal apoptosis in rats. Phenobarbital and phenytoin induce apoptosis at a therapeutically relevant dose range, lamotrigine and carbamazepine do so only at supratherapeutic doses or in polytherapy, and valproate does so even at subtherapeutic doses. Levetiracetam is devoid of pro apoptotic effects. Retigabine, a new-generation drug, acts uniquely by enhancing the M-type potassium current. Because its safety profile in developing animals is unstudied, we sought to determine if retigabine would induce apoptosis. METHODS: Postnatal day (P) 7 rat pups were treated with retigabine (5-30 mg/kg), vehicle (saline), or comparator drugs (phenobarbital, lamotrigine, levetiracetam, or carbamazepine). Cell death was assessed using amino-cupric-silver staining. A separate group of animals was treated repeatedly (three times over 24 h) with retigabine (15 mg/kg) or vehicle. To establish a pharmacokinetic profile for retigabine, we measured plasma and brain levels after drug treatment. RESULTS: Consistent with prior studies from our group and others, we found phenobarbital induced cell death throughout thalamus, nucleus accumbens, and several neocortical areas. By contrast, levetiracetam, lamotrigine, and carbamazepine were found to have no appreciable apoptotic effect on the aforementioned structures. Acute (single) exposure to retigabine, even at doses of 30 mg/kg, was also without effect on apoptosis. However, repeated (three times) exposure to retigabine triggered apoptosis in a subset of brain areas. The half-life of retigabine in plasma was 2.5 h, with appreciable concentrations reached in the brain within 1 h of administration. SIGNIFICANCE: These data demonstrate that retigabine, like many other anticonvulsant drugs, is capable of triggering neuronal apoptosis in the developing rat brain. Unlike other drugs, repeated dosing of retigabine was necessary to induce this effect. This may be due to its shorter half-life as compared to other drugs, such as phenobarbital. PMID- 26865188 TI - Total hip arthroplasty via the anterior approach: tips and tricks for primary and revision surgery. AB - PURPOSE: Described for the first time in the 1950s, the direct anterior approach to the hip has been gaining in popularity over the last decade following the trend of minimally invasive surgery. This paper provides an overview of the approach and its indications and various uses and focuses on its utility in the revision setting. A detailed overview of the technique including tips and tricks as well as an explanation of common errors are included. METHOD: Graphic and clinical study of the approach, indications and feasibility. RESULTS: The reported benefits of the direct anterior technique include enhanced post operative recovery and respect for all the innervation and vascularization territories. It has been shown to be safe and effective in revision settings, to decrease the occurrence of heterotopic ossification, to enhance the accuracy of acetabular cup positioning, and to improve post-operative rehabilitation while having comparable outcomes in terms of loosening or component failure. Additionally, thromboembolic events have been shown to be decreased compared to other approaches. The most common reported complications in the revision setting is intra-operative fracture. The decision of a surgeon to transition to this approach, however, comes with a learning curve and potentially detrimental complications if done improperly. DISCUSSION: In addition to its appeal in the primary setting, the approach could possibly be a solution to decrease the morbidity associated with revision surgery through its use of a fresh tissue plane not previously traumatized with the primary approach. PMID- 26865189 TI - Binding interactions of the peripheral stalk subunit isoforms from human V ATPase. AB - The mammalian peripheral stalk subunits of the vacuolar-type H(+)-ATPases (V ATPases) possess several isoforms (C1, C2, E1, E2, G1, G2, G3, a1, a2, a3, and a4), which may play significant role in regulating ATPase assembly and disassembly in different tissues. To better understand the structure and function of V-ATPase, we expressed and purified several isoforms of the human V-ATPase peripheral stalk: E1G1, E1G2, E1G3, E2G1, E2G2, E2G3, C1, C2, H, a1NT, and a2NT. Here, we investigated and characterized the isoforms of the peripheral stalk region of human V-ATPase with respect to their affinity and kinetics in different combination. We found that different isoforms interacted in a similar manner with the isoforms of other subunits. The differences in binding affinities among isoforms were minor from our in vitro studies. However, such minor differences from the binding interaction among isoforms might provide valuable information for the future structural-functional studies of this holoenzyme. PMID- 26865190 TI - Molecular Analysis of the Polymeric Glutenins with Gliadin-Like Characteristics That Were Produced by Acid Dispersion of Wheat Gluten. AB - We had earlier shown that the dispersion of wheat gluten in acetic acid solution conferred gliadin-like characteristics to the polymeric glutenins. To elucidate the molecular behavior of its polymeric glutenins, the characteristics of gluten powder prepared from dispersions with various types of acid were investigated in this study. Mixograph measurements showed that the acid-treated gluten powders, regardless of the type of acid, had dough properties markedly weakened in both resistance and elasticity properties, as though gliadin was supplemented. The polymeric glutenins extracted with 70% ethanol increased greatly in all acid treated gluten powders. Size exclusion HPLC and SDS-PAGE indicated that the behavior of polymeric glutenins due to acid treatment was attributed to their subunit composition rich in high molecular weight glutenin subunit (HMW-GS) and not their molecular size. The gluten prepared with the addition of NaCl in acid dispersion had properties similar to those of the control gluten. The results suggest that ionic repulsion induced by acid dispersion made the polymeric glutenins rich in HMW-GS disaggregate, and therefore, act like gliadins. PMID- 26865191 TI - Verification of gamma-Amino-Butyric Acid (GABA) Signaling System Components in Periodontal Ligament Cells In Vivo and In Vitro. AB - CNS key neurotransmitter gamma-amino-butyric acid (GABA) and its signaling components are likewise detectable in non-neuronal tissues displaying inter alia immunomodulatory functions. This study aimed at identifying potential glutamate decarboxylase (GAD)65 and GABA receptor expression in periodontal ligament (PDL) cells in vivo and in vitro, with particular regard to inflammation and mechanical loading. Gene expression was analyzed in human PDL cells at rest or in response to IL-1beta (5 ng/ml) or TNFalpha (5 ng/ml) challenge via qRT-PCR. Western blot determined constitutive receptor expression, and confocal laser scanning fluorescence microscopy visualized expression changes induced by inflammation. ELISA quantified GAD65 release. Immunocytochemistry was performed for GABA component detection in vitro on mechanically loaded PDL cells, and in vivo on rat upper jaw biopsies with mechanically induced root resorptions. Statistical significance was set at p < 0.05. GABAB1, GABAB2, GABAA1, and GABAA3 were ubiquitously expressed both on gene and protein level. GABAA2 and GAD65 were undetectable in resting cells, but induced by inflammation. GABAB1 exhibited the highest basal gene expression (6.97 % +/- 0.16). IL-1beta markedly increased GABAB2 on a transcriptional (57.28-fold +/- 12.40) and protein level seen via fluorescence microscopy. TNFalpha-stimulated PDL cells released GAD65 (3.68 pg/ml +/- 0.17 after 24 h, 5.77 pg/ml +/- 0.65 after 48 h). Immunocytochemistry revealed GAD65 expression in mechanically loaded PDL cells. In vivo, GABA components were varyingly expressed in an inflammatory periodontal environment. PDL cells differentially express GABA signaling components and secrete GAD65. Inflammation and mechanical loading regulate these neurotransmitter molecules, which are also detectable in vivo and are potentially involved in periodontal pathophysiology. PMID- 26865192 TI - Multicenter impact analysis of a model for predicting recurrent early-onset preeclampsia: A before-after study. AB - OBJECTIVE: This study aims to determine the impact of using a prediction model for recurrent preeclampsia to customize antenatal care in subsequent pregnancies. METHODS: We compared care consumption, pregnancy outcomes, and self-reported health state of two risk-based subgroups, and compared these to a reference group receiving standard care. RESULTS: We included a total of 311 women from 12 hospitals. Compared to standard care, recurrence-risk guided care did not lead to different outcomes or self-perceived health. CONCLUSION: Our study exemplifies that recurrence-risk-based stratification of antenatal care in former preeclampsia patients is feasible; it does not lead to worse pregnancy outcomes. PMID- 26865193 TI - Improving Treatment of Uncomplicated Diverticulitis: The Old Appendicitis. PMID- 26865194 TI - A Breathing Zirconium Metal-Organic Framework with Reversible Loss of Crystallinity by Correlated Nanodomain Formation. AB - The isoreticular analogue of the metal-organic framework UiO-66(Zr), synthesized with the flexible trans-1,4-cyclohexanedicarboxylic acid as linker, shows a peculiar breathing behavior by reversibly losing long-range crystalline order upon evacuation. The underlying flexibility is attributed to a concerted conformational contraction of up to two thirds of the linkers, which breaks the local lattice symmetry. X-ray scattering data are described well by a nanodomain model in which differently oriented tetragonal-type distortions propagate over about 7-10 unit cells. PMID- 26865195 TI - Effect of Renal and Hepatic Impairment on the Pharmacokinetics of Cabozantinib. AB - Cabozantinib is a tyrosine kinase inhibitor approved for the treatment of patients with progressive, metastatic medullary thyroid cancer. Two clinical pharmacology studies were conducted to characterize single-dose pharmacokinetics (PK) of cabozantinib in renally or hepatically impaired subjects. Study 1 enrolled 10 subjects, each with mild or moderate impairment of renal function; 12 healthy subjects were matched to the moderate group for age, sex, and body mass index (BMI). Study 2 enrolled 8 males each with mild or moderate hepatic impairment; 10 healthy males were matched to the moderate group for age, BMI, and ethnicity. All subjects received one 60 mg cabozantinib oral capsule dose followed by PK sampling over 21 days. Plasma concentration and protein binding were determined by liquid chromatography tandem mass spectrometry and equilibrium dialysis, respectively. PK parameters were computed using noncompartmental methods. Geometric least squared mean (LSM) ratios for plasma cabozantinib AUC0 infinity for impaired to normal organ function cohorts were (1) approximately 30% and 6% higher in subjects with mild and moderate renal impairment, respectively, and (2) approximately 81% and 63% higher in subjects with mild and moderate hepatic impairment, respectively. The percentage of unbound drug was slightly higher in both moderately impaired cohorts. No deaths or discontinuations due to adverse events occurred in either study. Cabozantinib should be used with caution in subjects with mild or moderate renal impairment. Subjects with mild or moderate hepatic impairment administered cabozantinib should be monitored closely for potential treatment-emergent drug toxicity that may necessitate a dose hold or reduction. PMID- 26865197 TI - Urate-Lowering Drugs and Prevention of Cardiovascular Disease: The Emerging Role of Xanthine Oxidase Inhibition. PMID- 26865199 TI - Allopurinol and Cardiovascular Outcomes in Adults With Hypertension. AB - Allopurinol lowers blood pressure in adolescents and has other vasoprotective effects. Whether similar benefits occur in older individuals remains unclear. We hypothesized that allopurinol is associated with improved cardiovascular outcomes in older adults with hypertension. Data from the United Kingdom Clinical Research Practice Datalink were used. Multivariate Cox-proportional hazard models were applied to estimate hazard ratios for stroke and cardiac events (defined as myocardial infarction or acute coronary syndrome) associated with allopurinol use over a 10-year period in adults aged >65 years with hypertension. A propensity matched design was used to reduce potential for confounding. Allopurinol exposure was a time-dependent variable and was defined as any exposure and then as high (>=300 mg daily) or low-dose exposure. A total of 2032 allopurinol-exposed patients and 2032 matched nonexposed patients were studied. Allopurinol use was associated with a significantly lower risk of both stroke (hazard ratio, 0.50; 95% confidence interval, 0.32-0.80) and cardiac events (hazard ratio, 0.61; 95% confidence interval, 0.43-0.87) than nonexposed control patients. In exposed patients, high-dose treatment with allopurinol (n=1052) was associated with a significantly lower risk of both stroke (hazard ratio, 0.58; 95% confidence interval, 0.36-0.94) and cardiac events (hazard ratio, 0.65; 95% confidence interval, 0.46-0.93) than low-dose treatment (n=980). Allopurinol use is associated with lower rates of stroke and cardiac events in older adults with hypertension, particularly at higher doses. Prospective clinical trials are needed to evaluate whether allopurinol improves cardiovascular outcomes in adults with hypertension. PMID- 26865198 TI - Medication Adherence and the Risk of Cardiovascular Mortality and Hospitalization Among Patients With Newly Prescribed Antihypertensive Medications. AB - The importance of adherence to antihypertensive treatments for the prevention of cardiovascular disease has not been well elucidated. This study evaluated the effect of antihypertensive medication adherence on specific cardiovascular disease mortality (ischemic heart disease [IHD], cerebral hemorrhage, and cerebral infarction). Our study used data from a 3% sample cohort that was randomly extracted from enrollees of Korean National Health Insurance. Study subjects were aged >=20 years, were diagnosed with hypertension, and started newly prescribed antihypertensive medication in 2003 to 2004. Adherence to antihypertensive medication was estimated as the cumulative medication adherence. Subjects were divided into good (cumulative medication adherence, >=80%), intermediate (cumulative medication adherence, 50%-80%), and poor (cumulative medication adherence, <50%) adherence groups. We used time-dependent Cox proportional hazards models to evaluate the association between medication adherence and health outcomes. Among 33 728 eligible subjects, 670 (1.99%) died of coronary heart disease or stroke during follow-up. Patients with poor medication adherence had worse mortality from IHD (hazard ratio, 1.64; 95% confidence interval, 1.16-2.31; P for trend=0.005), cerebral hemorrhage (hazard ratio, 2.19; 95% confidence interval, 1.28-3.77; P for trend=0.004), and cerebral infarction (hazard ratio, 1.92; 95% confidence interval, 1.25-2.96; P for trend=0.003) than those with good adherence. The estimated hazard ratios of hospitalization for cardiovascular disease were consistent with the mortality end point. Poor medication adherence was associated with higher mortality and a greater risk of hospitalization for specific cardiovascular diseases, emphasizing the importance of a monitoring system and strategies to improve medication adherence in clinical practice. PMID- 26865201 TI - Renal Resistive Index Predicts Postoperative Blood Pressure Outcome in Primary Aldosteronism. AB - The renal resistive index (RI) calculated by Doppler ultrasonography has been reported to be correlated with renal structural changes and outcomes in patients with essential hypertension or renal disease. However, little is known about this index in primary aldosteronism. In this prospective study, we examined the utility of this index to predict blood pressure (BP) outcome after adrenalectomy in patients with primary aldosteronism. We studied 94 patients with histopathologically proven aldosteronoma who underwent surgery. Parameters on renal function, including renal flow indices, were examined and followed up for 12 months postoperatively. The renal RI of the main, hilum, and interlobar arteries was significantly higher in patients with aldosteronoma compared with 100 control patients. BP, estimated glomerular filtration rate, and urinary albumin excretion significantly decreased after adrenalectomy. The resistive indices of all compartment arteries were significantly reduced 1 month after adrenalectomy and remained stable for 12 months. Patients whose interlobar RI was in the highest tertile at baseline had higher systolic BP after adrenalectomy than those whose RI was in the lowest tertile. Logistic regression analysis demonstrated that the RI of the interlobar and hilum arteries could be an independent predictive marker for intractable hypertension (systolic BP >=140 mm Hg, increased BP, taking >=3 antihypertensive agents, or increased number of agents) even after adrenalectomy. Therefore, in patients with aldosteronoma, the renal RI indicates partially reversible renal hemodynamics and renal structural damages that would influence postoperative BP outcome. PMID- 26865202 TI - Correction. PMID- 26865203 TI - An observational study of direct oral anticoagulant awareness indicating inadequate recognition with potential for patient harm. AB - Essentials Ignorance of direct oral anticoagulants' effects on coagulation tests may be a safety issue. An electronic questionnaire was sent to prescribers in NHS Grampian with 143 respondents. We found widespread evidence of inappropriate interpretation of the clinical scenarios given. The study suggests potential for patient harm due to lack of knowledge and education is required. SUMMARY: Background Lack of awareness of the nature of the direct oral anticoagulants (DOACs) combined with the poor correlation between routine coagulation test prolongation and the activity of these drugs represents a potential for patient harm. Objectives To establish the level of awareness of the different DOACs, and to assess whether prescribers were able to recognize the state of anticoagulation in a hypothetical patient. Methods and results An electronic questionnaire was sent by email to prescribers in our health board. Among 143 respondents, we found significant differences in awareness of the currently licensed drugs. Of the respondents, 88%, 80% and 50%, respectively, recognized rivaroxaban, dabigatran, and apixaban. When provided with a routine clinical situation, only 13.5%, 17.5% and 16.8%, respectively, recognized that the hypothetical patient was anticoagulated, and only 55-58% recognized that it was unsafe to proceed with an invasive procedure. Conclusion These results indicate a significant risk for patient harm related to lack of knowledge about this new group of frequently used drugs, and indicate that additional education and training on this subject are required. PMID- 26865205 TI - Cumulative Response to Sequences of Terror Attacks Varying in Frequency and Trajectory. AB - There is a paucity of research examining public response to the cumulative effects of multiple related extreme events over time. We investigated the separate and combined effects of frequency and trajectory of terrorist attacks. A scenario simulation of a series of gas station bombings in Southern California was developed to evaluate respondents' affect, risk perception, and intended avoidance behavior using a 3 (frequency; low vs. medium vs. high) by 3 (trajectory; increasing vs. constant vs. decreasing) factorial design. For each of the nine conditions, three videos were created to simulate news broadcasts documenting the attacks over a three-week period. A total of 275 respondents were included in the analysis. Results from analysis of covariances (ANCOVAs) indicate that trajectory of the sequential attacks (increasing or decreasing in frequency) predicts negative affect, risk perception, and avoidance behavior. In contrast, frequency predicts neither negative affect, positive affect, risk perception, nor intended avoidance behavior. Results from structural equation modeling (SEM) further indicate that the effect of negative affect on behavioral intention is mediated by risk perception and the effect of trajectory on risk perception is partially mediated by negative affect. In addition, both ANCOVAs and SEM model results suggest that (1) females experience less positive affect and perceive more risk than males, (2) respondents with higher income perceive more risk, and (3) younger respondents are more likely to modify their behavior to avoid the risk of future attacks. PMID- 26865200 TI - Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial. AB - Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness. PMID- 26865204 TI - Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria? AB - The definition of pulmonary fungal infections (PFI) according to the EORTC-MSG criteria may lack diagnostic sensitivity due to the possible presentation of PFI with different radiological pictures. We evaluated the hypothesis to apply less restrictive radiological criteria to define PFI in patients with acute myeloid leukaemia (AML) submitted to chemotherapy. Overall, 73 consecutive episodes of pulmonary infiltrates associated to positive serum galactomannan test or fungal isolation or galactomannan detection from respiratory specimens were considered. CT scans acquired at the onset of symptoms (time-0) and within 4 weeks (time-1) were analysed to identify specific (group A) or aspecific radiological signs (group B). Pulmonary infiltrates fulfilled the EORTC-MSG criteria in 49 patients (group A), whereas in 24 patients (group B) they did not reach the criteria due to aspecific CT findings at time-0. Eleven of 21 (52.4%) patients of the group B evaluable for the evolution of the radiological findings fulfilled EORTC-MSG criteria at time-1. All the analysed clinical and mycological characteristics, response to antifungal therapy and survival were comparable in the two groups. Our study seems to confirm the possibility to extend the radiological suspicion of PFI to less restrictive chest CT findings when supported by microbiological criteria in high-risk haematological patients. PMID- 26865206 TI - Melanoma Gene Expression Markers for Surveillance of Epidermolysis Bullosa Nevi Malignant Transformation. PMID- 26865207 TI - Time trends in socio-economic inequalities in stunting prevalence: analyses of repeated national surveys - CORRIGENDUM. PMID- 26865209 TI - Assessment of pelvic organ prolapse: a review. PMID- 26865210 TI - A broadening temperature sensitivity range with a core-shell YbEr@YbNd double ratiometric optical nanothermometer. AB - The chemical architecture of lanthanide doped core-shell up-converting nanoparticles can be engineered to purposely design the properties of luminescent nanomaterials, which are typically inaccessible to their homogeneous counterparts. Such an approach allowed to shift the up-conversion excitation wavelength from ~980 to the more relevant ~808 nm or enable Tb or Eu up conversion emission, which was previously impossible to obtain or inefficient. Here, we address the issue of limited temperature sensitivity range of optical lanthanide based nano-thermometers. By covering Yb-Er co-doped core nanoparticles with the Yb-Nd co-doped shell, we have intentionally combined temperature dependent Er up-conversion together with temperature dependent Nd -> Yb energy transfer, and thus have expanded the temperature response range DeltaT of a single nanoparticle based optical nano-thermometer under single ~808 nm wavelength photo-excitation from around DeltaT = 150 K to over DeltaT = 300 K (150-450 K). Such engineered nanocrystals are suitable for remote optical temperature measurements in technology and biotechnology at the sub-micron scale. PMID- 26865208 TI - Our first decade of experience in deep brain stimulation of the brainstem: elucidating the mechanism of action of stimulation of the ventrolateral pontine tegmentum. AB - The region of the pedunculopontine tegmental nucleus (PPTg) has been proposed as a novel target for deep brain stimulation (DBS) to treat levodopa resistant symptoms in motor disorders. Recently, the anatomical organization of the brainstem has been revised and four new distinct structures have been represented in the ventrolateral pontine tegmentum area in which the PPTg was previously identified. Given this anatomical reassessment, and considering the increasing of our experience, in this paper we revisit the value of DBS applied to that area. The reappraisal of clinical outcomes in the light of this revisitation may also help to understand the consequences of DBS applied to structures located in the ventrolateral pontine tegmentum, apart from the PPTg. The implantation of 39 leads in 32 patients suffering from Parkinson's disease (PD, 27 patients) and progressive supranuclear palsy (PSP, four patients) allowed us to reach two major conclusions. The first is that the results of the advancement of our technique in brainstem DBS matches the revision of brainstem anatomy. The second is that anatomical and functional aspects of our findings may help to explain how DBS acts when applied in the brainstem and to identify the differences when it is applied either in the brainstem or in the subthalamic nucleus. Finally, in this paper we discuss how the loss of neurons in brainstem nuclei occurring in both PD and PSP, the results of intraoperative recording of somatosensory evoked potentials, and the improvement of postural control during DBS point toward the potential role of ascending sensory pathways and/or other structures in mediating the effects of DBS applied in the ventrolateral pontine tegmentum region. PMID- 26865212 TI - PHASES and the natural history of unruptured aneurysms: science or pseudoscience? PMID- 26865211 TI - Increased level of tumour necrosis factor-alpha (TNF-alpha) on the skin of Japanese obese males: measured by quantitative skin blotting. AB - OBJECTIVE: A state of chronic inflammation, characterized by an increased level of tumour necrosis factor-alpha (TNF-alpha), is often found in the obese population. The negative effects of elevated TNF-alpha are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF-alpha in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF-alpha on the skin and to find the relationship between obesity and the level of TNF-alpha detected on the skin. METHODS: We used a novel, non-invasive method called quantitative skin blotting. Fifty-nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF-alpha detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis. RESULTS: Significant positive correlations were found between the levels of TNF alpha detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating. CONCLUSION: We found that high levels of TNF-alpha were detected on the skin of Japanese obese males, which implied the higher TNF-alpha in the skin. The elevation of skin TNF-alpha may be one factor related to skin fragility that is often found in obese individuals. PMID- 26865213 TI - Science and scepticism: Drug information, young men and counterpublic health. AB - It is perhaps no surprise that young people can be sceptical of the drug-related information they receive in school-based health education, health promotion and the media. Significant societal anxiety surrounds young people's drug consumption, so it is tempting to approach this scepticism as a problem to be solved. In this article, we look closely at a group of young Australian men (n = 25), all of whom hold deeply sceptical views about the drug information they received in schools, social marketing campaigns and public speech generally. We do not approach their scepticism as a problem to be solved in itself, however. Instead, we analyse its origins and how it relates to the way knowledge is constructed in drug education, health promotion and media accounts of drug use. To conceptualise this scepticism, we draw on Irwin and Michael's analysis of the changing relationship between science and society, Warner's theorisation of publics and counterpublics, and Race's related notion of 'counterpublic health'. The article organises the data into three key themes: scepticism about the accuracy of the claims made about drug risks and dangers, scepticism about representations of drug users, and scepticism about the motivations behind the health messages and drug policy in general. We then draw these different aspects of scepticism together to argue that the young men can be seen to constitute a health 'counterpublic', and we consider the implications of this approach, arguing for what has been described as a more diplomatic engagement between science and publics. PMID- 26865214 TI - The body mechanical: Building a caring community, crafting a functioning body. AB - When Hansen's disease became treatable in Taiwan in the mid-20th century, a group of Hansen's disease patients lost their sick role despite still having lingering symptoms that continued to evolve. While sociologists have explored in-depth situations in which the social role of the sick is ambiguous, few studies have investigated body experiences under liminality that requires sick people to find a new sick role. Living with lingering symptoms in a post-Hansen's disease world, the Hansen's disease patients I have studied face the conundrum of having to find an alternative sick role. Ethnographic fieldwork demonstrates how patients develop a specific set of body techniques that shape and are shaped by their membership in a patient community. Exploring the reinforcing projects of re embodiment and sociality around Hansen's disease, I argue that patients are able both to legitimate each other's feelings of sickness and to use those feelings to manage their illness and, as such, to collectively acquire an alternative sick role. Adding to existing discussions of active patients, this article identifies the body mechanical as a way of practicing active patienthood organized around fixing, trials, mending and functionality. PMID- 26865215 TI - Lipoxin A4 exerts protective effects against experimental acute liver failure by inhibiting the NF-kappaB pathway. AB - Although rare, acute liver failure (ALF) is associated with high levels of mortality, warranting the development of novel therapies. Nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) play roles in ALF. Lipoxin A4 (LXA4) has been shown to alleviate inflammation in non-hepatic tissues. In the present study, we explored whether LXA4 exerted hepatoprotective effects in a rat model of ALF. A rat model of ALF was generated by intraperitoneal injections of D-galactosamine (300 mg/kg) and lipopolysaccharide (50 ug/kg). Animals were randomly assigned to: control group (no ALF); model group (ALF); and the groups treated with a low dose (0.5 ug/kg), medium dose (1 ug/kg), and high dose (2 ug/kg) of LXA4 (all with ALF); and pyrrolidine dithiocarbamate (PDTC)-treated group (ALF and 100 mg/kg PDTC, an inhibitor of NF-kappaB). Liver histology was measured using H&E staining, serum levels by ELISA, and liver mRNA expression was measured by RT-PCR for the detection of the pro-inflammatory cytokines TNF-alpha and IL-6. Liver cell apoptosis (as measured using the TUNEL method and examining caspase-3 activity), and Kupffer cell NF-kappaB activity [using an electrophoretic mobility shift assay (EMSA)] were examined. Serum levels of transaminases, TNF-alpha and interleukin-6 (IL-6) were substantially higher in the model group compared to controls. In the model group, significant increases in TNF-alpha and IL-6 mRNA expression, TUNEL-positive cells, and caspase-3 activity in the liver tissue were noted. LXA4 improved liver pathology and significantly decreased the indicators of inflammatory response and apoptosis in a dose-dependent manner. High-dose LXA4 provided better protection than PDTC. LXA4 administration significantly decreased NF-kappaB expression in hepatocytes and Kupffer cells. These results indicated that LXA4 inhibited NF-kappaB activation, reduced the secretion of pro inflammatory cytokines, and inhibited apoptosis of liver cells, thereby exerting protective effects against ALF. PMID- 26865216 TI - Identification of candidate genes involved in Witches' broom disease resistance in a segregating mapping population of Theobroma cacao L. in Brazil. AB - BACKGROUND: Witches' broom disease (WBD) caused by the fungus Moniliophthora perniciosa is responsible for considerable economic losses for cacao producers. One of the ways to combat WBD is to plant resistant cultivars. Resistance may be governed by a few genetic factors, mainly found in wild germplasm. RESULTS: We developed a dense genetic linkage map with a length of 852.8 cM that contains 3,526 SNPs and is based on the MP01 mapping population, which counts 459 trees from a cross between the resistant 'TSH 1188' and the tolerant 'CCN 51' at the Mars Center for Cocoa Science in Barro Preto, Bahia, Brazil. Seven quantitative trait loci (QTL) that are associated with WBD were identified on five different chromosomes using a multi-trait QTL analysis for outbreeders. Phasing of the haplotypes at the major QTL region on chromosome IX on a diversity panel of genotypes clearly indicates that the major resistance locus comes from a well known source of WBD resistance, the clone 'SCAVINA 6'. Various potential candidate genes identified within all QTL may be involved in different steps leading to disease resistance. Preliminary expression data indicate that at least three of these candidate genes may play a role during the first 12 h after infection, with clear differences between 'CCN 51' and 'TSH 1188'. CONCLUSIONS: We combined the information from a large mapping population with very distinct parents that segregate for WBD, a dense set of mapped markers, rigorous phenotyping capabilities and the availability of a sequenced genome to identify several genomic regions that are involved in WBD resistance. We also identified a novel source of resistance that most likely comes from the 'CCN 51' parent. Thanks to the large population size of the MP01 population, we were able to pick up QTL and markers with relatively small effects that can contribute to the creation and selection of more tolerant/resistant plant material. PMID- 26865218 TI - Quercetin mitigates valinomycin-induced cellular stress via stress-induced metabolism and cell uptake. AB - SCOPE: Intestinal cells are constantly exposed to luminal toxins. In this study, we investigated the effect of cellular stress caused by valinomycin, which is structurally and functionally similar to the bacterial toxin cereulide, on quercetin metabolism and cellular localization in undifferentiated cells. METHODS AND RESULTS: Coadministration of quercetin and valinomycin (50 MUM quercetin/0.05 MUM valinomycin) reduced intracellular reactive oxygen species content and increased cell viability (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) of Caco-2 cells compared to valinomycin-only (0.05 MUM) treatment. Quercertin was effectively metabolized into methyl, glucuronide, and sulfate conjugates, which were mostly secreted into to the culture medium. Three different O-methylated quercetin isomers were detected. Two were exported from the cells and one remained intracellularly. Further, valinomycin caused an increase in the intracellular accumulation of O-methylated quercetin metabolites compared to cells treated only with quercetin. In valinomycin-untreated cells, quercetin and O-methylated quercetin metabolite were localized in the cell membrane, whereas valinomycin treatment resulted in their uptake by the cells. CONCLUSION: This is the first report on the change in metabolism, localization, and accumulation of O-methylated quercetin metabolites in undifferentiated Caco-2 cells as a response during stress caused by valinomycin. These results indicate a potential cellular stress response mechanism in undifferentiated Caco-2 cells, which adds novel insights into the mechanisms of flavonoid cellular bioactivity. PMID- 26865217 TI - Genomic study of the Ket: a Paleo-Eskimo-related ethnic group with significant ancient North Eurasian ancestry. AB - The Kets, an ethnic group in the Yenisei River basin, Russia, are considered the last nomadic hunter-gatherers of Siberia, and Ket language has no transparent affiliation with any language family. We investigated connections between the Kets and Siberian and North American populations, with emphasis on the Mal'ta and Paleo-Eskimo ancient genomes, using original data from 46 unrelated samples of Kets and 42 samples of their neighboring ethnic groups (Uralic-speaking Nganasans, Enets, and Selkups). We genotyped over 130,000 autosomal SNPs, identified mitochondrial and Y-chromosomal haplogroups, and performed high coverage genome sequencing of two Ket individuals. We established that Nganasans, Kets, Selkups, and Yukaghirs form a cluster of populations most closely related to Paleo-Eskimos in Siberia (not considering indigenous populations of Chukotka and Kamchatka). Kets are closely related to modern Selkups and to some Bronze and Iron Age populations of the Altai region, with all these groups sharing a high degree of Mal'ta ancestry. Implications of these findings for the linguistic hypothesis uniting Ket and Na-Dene languages into a language macrofamily are discussed. PMID- 26865220 TI - Current Rehabilitation Practices for Children with Cerebral Palsy: Focus and Gaps. AB - AIMS: To describe the focus of therapy practices in occupational and physical therapy for school-aged children with cerebral palsy, and better understand whether it is congruent with recommended practices. METHODS: A Canada-wide Web based survey was completed by 62 occupational and 61 physical therapists to identify problems, assessments, and treatment interventions for two case-based scenarios. Data were coded using the International Classification of Functioning, Disability and Health (ICF) definitions for "body functions and structure," "activity and participation," and "environment." RESULTS: Physical therapists, in comparison to occupational therapists, were more likely to select interventions classed in the "body functions and structure" category (34-42% and 18-20%, respectively). Both professions focused on "activity and participation" (34-61%) when identifying problems, assessing, and intervening; attention, however, was mainly directed towards task-oriented activities such as activities of daily living and mobility. Participation in leisure or community-based activities received less attention (2-15%). The environment received limited attention for problems and assessments (4-25%), though it was an important focus of intervention (19-37%). CONCLUSIONS: While body functions and structure are well addressed, other ICF elements, specifically participation, are poorly integrated into practice. The emerging focus on the environment in therapy intervention, by modifying the context rather than changing aspects of the child, is consistent with current approaches and evidence. Knowledge translation implementation initiatives are recommended to bridge identified gaps. PMID- 26865219 TI - Rural-to-urban migration and risk of hypertension: longitudinal results of the PERU MIGRANT study. AB - Urbanization can be detrimental to health in populations due to changes in dietary and physical activity patterns. The aim of this study was to determine the effect of migration on the incidence of hypertension. Participants of the PERU MIGRANT study, that is, rural, urban and rural-to-urban migrants, were re evaluated after 5 years after baseline assessment. The outcome was incidence of hypertension; and the exposures were study group and other well-known risk factors. Incidence rates, relative risks (RRs) and population attributable fractions (PAFs) were calculated. At baseline, 201 (20.4%), 589 (59.5%) and 199 (20.1%) participants were rural, rural-to-urban migrant and urban subjects, respectively. Overall mean age was 47.9 (s.d.+/-12.0) years, and 522 (52.9%) were female. Hypertension prevalence at baseline was 16.0% (95% confidence interval (CI) 13.7-18.3), being more common in urban group; whereas pre-hypertension was more prevalent in rural participants (P<0.001). Follow-up rate at 5 years was 94%, 895 participants were re-assessed and 33 (3.3%) deaths were recorded. Overall incidence of hypertension was 1.73 (95%CI 1.36-2.20) per 100 person years. In multivariable model and compared with the urban group, rural group had a greater risk of developing hypertension (RR 3.58; 95%CI 1.42-9.06). PAFs showed high waist circumference as the leading risk factor for the hypertension development in rural (19.1%), migrant (27.9%) and urban (45.8%) participants. Subjects from rural areas are at higher risk of developing hypertension relative to rural-urban migrant or urban groups. Central obesity was the leading risk factor for hypertension incidence in the three population groups. PMID- 26865222 TI - Severe hyperkalemia presenting with wide-complex tachycardia in a puppy with acute kidney injury secondary to leptospirosis. AB - OBJECTIVE: To describe a case of hyperkalemia coinciding with wide-complex tachycardia (WCT) in a dog with acute kidney injury secondary to leptospirosis infection. CASE SUMMARY: An 11-week-old Golden Retriever-Standard Poodle cross puppy was referred for acute kidney injury and hepatopathy. WCT coinciding with marked hyperkalemia was identified on presentation. Tachycardia persisted until resolution of hyperkalemia. NEW OR UNIQUE INFORMATION PROVIDED: To our knowledge, this is the first report of severe hyperkalemia presenting with WCT in a dog. Hyperkalemia should be considered a differential for WCT in dogs. PMID- 26865221 TI - Gold Nanoparticles Doped with (199) Au Atoms and Their Use for Targeted Cancer Imaging by SPECT. AB - Gold nanoparticles have been labeled with various radionuclides and extensively explored for single photon emission computed tomography (SPECT) in the context of cancer diagnosis. The stability of most radiolabels, however, still needs to be improved for accurate detection of cancer biomarkers and thereby monitoring of tumor progression and metastasis. Here, the first synthesis of Au nanoparticles doped with (199)Au atoms for targeted SPECT tumor imaging in a mouse triple negative breast cancer (TNBC) model is reported. By directly incorporating (199)Au atoms into the crystal lattice of each Au nanoparticle, the stability of the radiolabel can be ensured. The synthetic procedure also allows for a precise control over both the radiochemistry and particle size. When conjugated with D Ala1-peptide T-amide, the Au nanoparticles doped with (199)Au atoms can serve as a C-C chemokine receptor 5 (CCR5)-targeted nanoprobe for the sensitive and specific detection of both TNBC and its metastasis in a mouse tumor model. PMID- 26865223 TI - Solution and Solid-State Analysis of Binding of 13-Substituted Berberine Analogues to Human Telomeric G-quadruplexes. AB - The interaction between 13-phenylalkyl and 13-diphenylalkyl berberine derivatives (NAX) and human telomeric DNA G4 structures has been investigated by both spectroscopic and crystallographic methods. NAX042 and NAX053 are the best compounds improving the performance of the natural precursor berberine. This finding is in agreement with the X-ray diffraction result for the NAX053-Tel12 adduct, showing the ligand which interacts via pi-stacking, sandwiched at the interface of two symmetry-related quadruplex units, with its benzhydryl group contributing to the overall stability of the adduct by means of additional pi stacking interactions with the DNA residues. The berberine derivatives were also investigated for their cytotoxic activity towards a panel of human cancer cell lines. Compounds NAX042 and NAX053 affect the viability of cancer cell lines in a dose-dependent manner. PMID- 26865224 TI - CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation. PMID- 26865225 TI - Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer. PMID- 26865226 TI - Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo. PMID- 26865227 TI - BAX inhibitor-1 enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger: the alteration of mitochondrial function. PMID- 26865229 TI - Exploring structural phase transitions of ion crystals. AB - Phase transitions have been a research focus in many-body physics over past decades. Cold ions, under strong Coulomb repulsion, provide a repealing paradigm of exploring phase transitions in stable confinement by electromagnetic field. We demonstrate various conformations of up to sixteen laser-cooled (40)Ca(+) ion crystals in a home-built surface-electrode trap, where besides the usually mentioned structural phase transition from the linear to the zigzag, two additional phase transitions to more complicated two-dimensional configurations are identified. The experimental observation agrees well with the numerical simulation. Heating due to micromotion of the ions is analysed by comparison of the numerical simulation with the experimental observation. Our investigation implies very rich and complicated many-body behaviour in the trapped-ion systems and provides effective mechanism for further exploring quantum phase transitions and quantum information processing with ultracold trapped ions. PMID- 26865228 TI - Urinary inorganic arsenic concentrations and semen quality of male partners of subfertile couples in Tokyo. AB - Inorganic arsenic (iAs) has been known as a testicular toxicant in experimental rodents. Possible association between iAs exposure and semen quality (semen volume, sperm concentration, and sperm motility) was explored in male partners of couples (n = 42) who visited a gynecology clinic in Tokyo for infertility consultation. Semen parameters were measured according to WHO guideline at the clinic, and urinary iAs and methylarsonic acid (MMA), and dimethylarsinic acid concentrations were determined by liquid chromatography-hydride generation-ICP mass spectrometry. Biological attributes, dietary habits, and exposure levels to other chemicals with known effects on semen parameters were taken into consideration as covariates. Multiple regression analyses and logistic regression analyses did not find iAs exposure as significant contributor to semen parameters. Lower exposure level of subjects (estimated to be 0.5 MUg kg(-1) day( 1)) was considered a reason of the absence of adverse effects on semen parameters, which were seen in rodents dosed with 4-7.5 mg kg(-1). PMID- 26865230 TI - Demodex castoris sp. nov. (Acari: Demodecidae) parasitizing Castor fiber (Rodentia), and other parasitic arthropods associated with Castor spp. AB - A new species of demodecid mite, Demodex castoris sp. nov. (Acari: Prostigmata: Demodecidae), is described based on adult stages from the skin of the nasal region of the Eurasian beaver Castor fiber Linnaeus, 1758, collected in Poland. This is the first detection of a representative demodecid mite in rodents of the suborder Castorimorpha and also represents the first detection of a skin mite in Eurasian beavers. The new species is a small skin mite (average 173 um in length) characterized by sexual dimorphism related to body proportions. D. castoris sp. nov. was observed in 4 out of 6 beavers examined (66.6%), with a mean intensity of 10.8 and an intensity range of 2-23 ind. host(-1). This paper also contains a checklist of parasitic arthropods known from Castor spp. PMID- 26865231 TI - Infection and transmission heterogeneity of a multi-host pathogen (Batrachochytrium dendrobatidis) within an amphibian community. AB - The majority of parasites infect multiple hosts. As the outcome of the infection is different in each of them, most studies of wildlife disease focus on the few species that suffer the most severe consequences. However, the role that each host plays in the persistence and transmission of infection can be crucial to understanding the spread of a parasite and the risk it poses to the community. Current theory predicts that certain host species can modulate the infection in other species by amplifying or diluting both infection prevalence and infection intensity, both of which have implications for disease risk within those communities. The fungus Batrachochytrium dendrobatidis (Bd), the causal agent of the disease chytridiomycosis, has caused global amphibian population declines and extinctions. However, not all infected species are affected equally, and thus Bd is a good example of a multi-host pathogen that must ultimately be studied with a community approach. To test whether the common midwife toad Alytes obstetricans is a reservoir and possible amplifier of infection of other species, we used experimental approaches in captive and wild populations to determine the effect of common midwife toad larvae on infection of other amphibian species found in the Penalara Massif, Spain. We observed that the most widely and heavily infected species, the common midwife toad, may be amplifying the infection loads in other species, all of which have different degrees of susceptibility to Bd infection. Our results have important implications for performing mitigation actions focused on potential 'amplifier' hosts and for better understanding the mechanisms of Bd transmission. PMID- 26865232 TI - Infectious pancreatic necrosis virus (IPNV) strain with genetic properties associated with low pathogenicity at Finnish fish farms. AB - Infectious pancreatic necrosis (IPN) is a contagious viral disease of fish that causes economic losses in aquaculture worldwide. In Finland, IPN virus (IPNV) has been isolated since 1987 from adult fish showing no signs of clinical disease at fish farms located in the coastal areas of the Baltic Sea. The inland area of Finland, however, remained free of IPN until 2012, when fish on several rainbow trout farms were diagnosed IPNV-positive. The fish mortalities detected at the farms were low, but clinical signs and histopathological changes typical for IPNV infection were seen in juvenile salmonids. IPNV was isolated at high water temperatures up to 22 degrees C. In 2013 and 2014, IPNV detections continued at inland farms, indicating that infections have spread. The aim of this study was to describe the epidemiology of the outbreak and to characterise the Finnish inland IPNV isolates using histopathological, immunohistochemical and genetic approaches. In order to determine the epidemiological origin of the inland IPNV infections, the partial viral capsid protein (VP2) gene sequences of the inland IPNV isolates were compared with the sequences of the isolates from the coastal farms. Based on the genetic analysis, the inland isolates belong to IPNV Genogroup 2 (Serotype A3/Ab), and the origin of the isolates appears to be one or several coastal fish farms. PMID- 26865233 TI - Evaluation of marine bacteriocinogenic enterococci strains with inhibitory activity against fish-pathogenic Gram-negative bacteria. AB - Use of lactic acid bacteria (LAB) as probiotics may provide an alternative to the use of antibiotics in aquaculture. LAB strains isolated from wild fish viscera and skin were evaluated for bacteriocin production and safety aspects (lack of antibiotic resistance, production of virulence factors). 16S rRNA gene sequences revealed the presence of Enterococcus faecium (13 isolates) and Lactococcus lactis (3 isolates) from fish samples. Pulsed-field gel electrophoresis analyses of the 13 enterococci isolates showed that they were all clustered, with greater than 95% similarity. However, RAPD analysis revealed significant molecular diversity between enterococci strains. Six enterococci strains were chosen and evaluated for their antibacterial activities. These strains produced a bacteriocin-like substance and exhibited a broad spectrum of inhibition against pathogenic bacteria isolated from diseased fish, including Streptococcus parauberis, Vagococcus spp., and Carnobacterium maltaromaticum, and in particular against the Gram-negative bacteria Flavobacterium frigidarium, Vibrio pectenicida, V. penaeicida, and Photobacterium damselae. The inhibition activity towards bacterial indicator strains was at a maximum when bacteria were grown at 37 degrees C. However, bacteriocin production was observed at 15 degrees C after 12 h of incubation. Only structural genes of enterocins A and B were detected by PCR in the 6 enterococci strains, suggesting the production of these enterocins. In addition, these strains did not harbor any virulence factors or any significant antibiotic resistance, and they tolerated bile. Our results suggest that enterococci are an important part of the bacterial flora of fish and that some strains have the potential to be used as probiotics. PMID- 26865234 TI - Prevalence of the pathogen Aphanomyces astaci in freshwater crayfish populations in Croatia. AB - The Oomycete Aphanomyces astaci is an obligate crayfish parasite that co-evolved with American crayfish species, and they therefore generally live in a balanced relationship. On the contrary, European native crayfish are highly susceptible to A. astaci, and infestation with it causes development of the lethal disease termed crayfish plague. Until now, 5 A. astaci strains have been described from the freshwater crayfish present in Europe. In this study we aimed to investigate the occurrence of the pathogen A. astaci in Croatian native and non-native crayfish populations, as well as to genotype established strains using microsatellite markers and obtain information on the pathogen's epidemiology. Our results showed that the pathogen is widespread in both native and non-native crayfish populations. Agent level, when positive, in non-native crayfish was generally low; in native species it was higher. Genotyping from microsatellites proved the presence of the B (Ps) strain in non-native species (Pacifastacus leniusculus), while the A (As) strain was detected from viable native species (Astacus astacus and Austropotamobius torrentium) that are distributed in areas lacking non-native crayfish. The genotype from A. torrentium differed from a typical A (As) by 1 allele. Strain B (Ps) was identified in native Astacus leptodactylus from the population that co-occurs with P. leniuscuslus. Interestingly, in 1 A. leptodactylus population both A (As) and B (Ps) strains were present. PMID- 26865235 TI - Bonamia ostreae in the New Zealand oyster Ostrea chilensis: a new host and geographic record for this haplosporidian parasite. AB - Previous reports of the haplosporidian parasite Bonamia ostreae have been restricted to the Northern Hemisphere, including Europe, and both eastern and western North America. This species is reported for the first time in New Zealand infecting the flat oyster Ostrea chilensis. Histological examination of 149 adult oysters identified 119 (79.9%) infected with Bonamia microcells. Bonamia generic PCR of several oysters followed by DNA sequencing of a 300 bp portion of the 18S rDNA gene produced a 100% match with that of B. ostreae. All DNA-sequenced products also produced a B. ostreae PCR-restriction fragment length polymorphism (PCR-RFLP) profile. Bonamia species-specific PCRs further detected single infections of B. exitiosa (2.7%), B. ostreae (40.3%), and concurrent infections (53.7%) with these 2 Bonamia species identifying overall a Bonamia prevalence of 96.6%. Detailed histological inspection revealed 2 microcell types. An infection identified by PCR as B. ostreae histologically presented small microcells (mean +/- SE diameter = 1.28 +/- 0.16 um, range = 0.9-2 um, n = 60) commonly with eccentric nuclei. A B. exitiosa infection exhibited larger microcells (mean +/- SE diameter = 2.12 +/- 0.27 um, range = 1.5-4 um, n = 60) with more concentric nuclei. Concurrent infections of both Bonamia species, as identified by PCR, exhibited both types of microcells. DNA barcoding of the B. ostreae-infected oyster host confirmed the identification as O. chilensis. A suite of other parasites that accompany O. chilensis are reported here for the first time in mixed infection with B. ostreae including apicomplexan X (76.5%), Microsporidium rapuae (0.7%) and Bucephalus longicornutus (30.2%). PMID- 26865236 TI - Identification and characterization of ostreid herpesvirus 1 associated with massive mortalities of Scapharca broughtonii broodstocks in China. AB - In the early summer of 2012 and 2013, mass mortalities of blood ark shell (Scapharca [Anadara] broughtonii), broodstocks were reported in several hatcheries on the coast of northern China. Clinical signs including slow response, gaping valves and pale visceral mass were observed in diseased individuals. In response to these reported mortalities, 238 samples were collected from hatcheries at 6 sites. Microscopic changes including lysed connective tissue, dilation of the digestive tubules, eosinophilic inclusion bodies, nuclear chromatin margination and pyknosis were found in affected animals. Transmission electron microscopy (TEM) revealed herpes-like viral particles within the connective tissue of the mantle. Quantative PCR (qPCR) and nested PCR (nPCR) analysis using primers specific for ostreid herpesvirus 1 (OsHV 1) indicated significant higher prevalence of OsHV-1 DNA in cases associated with mass mortalities than those without mass mortalities (p = 0.0012 for qPCR, p < 0.0001 for nPCR). qPCR also indicated that samples associated with mass mortalities carried high viral DNA loads, while the loads in apparently healthy samples were significantly lower (t = 3.15, df = 92, p = 0.002). Sequence analysis of the C2/C6 region of nPCR products revealed 5 newly described variants, which were closely related to each other. Phylogenetic analysis of the 5 virus variants and 48 virus variants reported in previous studies identified 2 main phylogenetic groups, and the 5 virus variants identified here were allocated to a separate subclade. To our knowledge, this is the first report of mass mortalities of bivalve broodstocks associated with OsHV-1 infection. PMID- 26865237 TI - Microbial transcriptome profiling of black band disease in a Faviid coral during a seasonal disease peak. AB - The etiology of black band disease (BBD), a persistent, globally distributed coral disease characterized by a dark microbial mat, is still unclear. A metatranscriptomics approach was used to unravel the roles of the major mat constituents in the disease process. By comparing the transcriptomes of the mat constituents with those of the surface microbiota of diseased and healthy corals, we showed a shift in bacterial composition and function in BBD-affected corals. mRNA reads of Cyanobacteria, Bacteroidetes and Firmicutes phyla were prominent in the BBD mat. Cyanobacterial adenosylhomocysteinase, involved in cyanotoxin production, was the most transcribed gene in the band consortium. Pathogenic and non-pathogenic forms of Vibrio spp., mainly transcribing the thiamine ABC transporter, were abundant and highly active in both the band and surface tissues. Desulfovibrio desulfuricans was the primary producer of sulfide in the band. Members of the Bacilli class expressed high levels of rhodanese, an enzyme responsible for cyanide and sulfide detoxification. These results offer a first look at the varied functions of the microbiota in the disease mat and surrounding coral surface and enabled us to develop an improved functional model for this disease. PMID- 26865238 TI - Breast milk nutrient content and infancy growth. AB - AIM: Benefits of human breast milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient content. We tested the hypothesis that differential HM total calorie content (TCC) or macronutrient contents may be associated with infancy growth. METHODS: HM hindmilk samples were collected at ages 4-8 weeks from 614 mothers participating in a representative birth cohort, with repeated infancy anthropometry. HM triglyceride (fat), lipid analytes and lactose (carbohydrate) were measured by (1) H-NMR, and protein content by the Dumas method. TCC and %macronutrients were determined. RESULTS: In 614 HM samples, fat content was as follows: [median(IQR)]: 2.6 (1.7-3.6) g/100 mL, carbohydrate: 8.6 (8.2-8.8) g/100 mL, protein: 1.2 (1.1-1.2) g/100 mL; TCC: 61.8 (53.7-71.3) kcal/100 mL. HM of mothers exclusively breast feeding vs. mixed feeding was more calorific with higher %fat, lower %carbohydrate and lower %protein. Higher HM TCC was associated with lower 12-months body mass index (BMI)/adiposity, and lower 3-12 months gains in weight/BMI. HM %fat was inversely related to 3-12 months gains in weight, BMI and adiposity, whereas %carbohydrate was positively related to these measures. HM %protein was positively related to 12-months BMI. CONCLUSION: HM analysis showed wide variation in %macronutrients. Although data on milk intakes were unavailable, our findings suggest functional relevance of HM milk composition to infant growth. PMID- 26865239 TI - Highly bendable bilayer-type photo-actuators comprising of reduced graphene oxide dispersed in hydrogels. AB - To avoid the problem of reduced graphene oxide (rGO) restacking in aqueous solution, the preparation of light-responsive poly(N-isopropylacrylamide) incorporating rGO (PNIPAm/rGO) was achieved by the chemical reduction of GO dispersed in the hydrogel matrix. Due to the enhanced photothermal efficiency of the rGO, the prepared PNIPAm/rGO underwent large volume reductions in response to irradiation by visible light of modest intensity. With respect to potential applications, bilayer-type photo-actuators comprising a PNIPAm/rGO active layer and poly(acrylamide) passive layer were fabricated; these achieved a full bending motion upon visible-light exposure. Adjusting the swelling ratio of each layer in the initial state yielded bidirectional photo-actuators that showed the active motion of turning inside out. Furthermore, we demonstrated that the fabricated actuation system would exhibit controlled bending motion in response to solar radiation. PMID- 26865240 TI - Obstructive sleep apnoea syndrome increases source-confusion errors: A pilot study. AB - We explored external source monitoring (i.e., discrimination between memories of two externally derived sources) in patients with obstructive sleep apnoea syndrome (OSAS). Our specific aim was to ascertain whether, relative to controls, patients exhibit more source-confusion errors when there are similarities between two external memory sources. We recruited 22 patients with OSAS and 22 controls matched for sex, age, and education. The experimental procedure we used came in three phases. First, participants viewed a target film. Second, they were shown a mixed set of photographs, some taken from the film (target photographs), others not (photographs taken from other films not viewed by participants; lures). Lures differed either conceptually or perceptually from the target film. Third, the following day, participants were shown a set of photographs and urged to determine whether the photographs were taken from the target film or whether they were images they had seen for the first time in Phase 2. Patients correctly attributed the same number of target photographs to the target film as controls. By contrast, they incorrectly attributed more lures to the target film than controls did, especially when the lures were semantically similar to the film (perceptual lures). Both perceptual and conceptual source-confusion errors were significantly correlated with oxygen desaturation during sleep. Results suggest that the higher number of source-confusion errors observed in patients with OSAS was linked to an impaired ability to recollect specific perceptual details of the study items and that hypoxia is the main contributing factor to this deficit. PMID- 26865241 TI - Efficacy of rituximab therapy against intractable steroid-resistant nephrotic syndrome. AB - BACKGROUND: Some cases of childhood steroid-resistant nephrotic syndrome (SRNS) are intractable. We examined the cases of three patients with SRNS resistant to various treatment, but who achieved complete remission after being treated with rituximab (RTX) followed by methylprednisolone pulse (MP) therapy. METHODS: A retrospective chart review of all new-onset SRNS in the period from January 1997 to December 2013 was performed. Three of the 13 patients who received conventional treatment continued to have NS for >6 months, despite also being treated with immunosuppressants and receiving frequent albumin treatment. In addition, two of the patients received plasma exchange therapy, but it was ineffective. Therefore, RTX was used once a week for 4 weeks, followed by several courses of MP therapy. RESULTS: Two of the three intractable SRNS patients achieved complete remission after treatment with RTX followed by MP therapy, and the remaining patient achieved incomplete remission after the first round of this treatment. That patient subsequently achieved complete remission after the second round of the treatment. RTX did not cause any serious side-effects, and all three patients had normal renal function at the final observation. CONCLUSIONS: Complete remission was achieved in all 13 SRNS patients. RTX followed by MP therapy might be effective against SRNS refractory to conventional treatments and requiring frequent albumin treatment. Prospective clinical study examining the effectiveness and safety of this approach is required. PMID- 26865242 TI - Dizziness and death: An imbalance in mortality. AB - OBJECTIVES/HYPOTHESIS: To determine if dizziness is an independent risk factor for mortality among adults in the United States. STUDY DESIGN: Cross-sectional analysis using the National Health Interview Survey (NHIS). METHODS: Adult respondents in the 2008 NHIS were evaluated. Demographic information (gender, race, ethnicity, education level), prevalence of dizziness, mortality rates, and leading causes of death (cardiovascular disease, cancer, diabetes, cerebrovascular disease) were collected and analyzed. The association between dizziness and subsequent mortality was determined adjusting for demographic and other disease factors. RESULTS: Among 213.6 +/- 3.5 million adult Americans, 23.8 +/- 0.7 million reported dizziness in the past 12 months (11.1% +/- 0.3%; mean age, 45.9 +/- 0.2 years; 51.7% +/- 0.5% female). The mortality rate among the group without dizziness in the preceding 12 months was 2.6% +/- 0.1%, compared to the dizzy group at 9.0% +/- 0.7%. After adjusting for gender and age, there was a statistically significant association between dizziness and mortality (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.8-2.8). After adjusting for all covariates including age, ethnicity, race, gender, diabetes, cardiovascular, cerebrovascular disease, cancer, and grade level, dizziness remained an independent predictor of increased mortality (adjusted OR: 1.7, 95% CI: 1.36 2.18). CONCLUSIONS: Approximately 11% of adult Americans reported dizziness or balance problems in the preceding 12 months. Adults with dizziness have a greater mortality rate than nondizzy adults. Even after adjusting for covariates, there was a significant association between dizziness and mortality. Screening for dizziness as a risk factor for mortality may be warranted. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2134-2136, 2016. PMID- 26865245 TI - The epidemiology of in-hospital cardiac arrests in Australia and New Zealand. AB - BACKGROUND: The epidemiology of in-hospital cardiac arrests (IHCA) in Australia and New Zealand (ANZ) has not been systematically assessed. AIM: To conduct a systematic review of the frequency, characteristics and outcomes of adult IHCA in ANZ. METHODS: Medline search for studies published in 1964-2014 using MeSH terms 'arrest AND hospital AND Australia', 'arrest AND hospital AND New Zealand', 'inpatient AND arrest AND Australia' and 'inpatient AND arrest AND New Zealand'. RESULTS: We screened 934 studies, analysed 50 and included 30. Frequency of IHCA ranged from 1.31 to 6.11 per 1000 admissions in 4 population studies and 0.58 to 4.59 per 1000 in 16 cohort studies. The frequency was 4.11 versus 1.32 per 1000 admissions in hospitals with rapid response system (RRS) compared with those without (odds ratio: 0.32; 95% confidence interval 0.28-0.37; P < 0.001). On aggregate, the initial cardiac rhythm was ventricular tachycardia/fibrillation in 31.4% (range 19.0-48.8%) in 10 studies reporting such data. On aggregate, IHCA were witnessed in 80.2% cases (three studies) and monitored patients in 53.4% cases (four studies). Details of life support were poorly documented. On aggregate, return of spontaneous circulation occurred in 46.0% of patients. Overall, 74.6% (range 59.4-77.5%) died in-hospital but survival was higher among monitored or younger patients, in those with a shockable rhythm, or during working hours. CONCLUSION: IHCA are uncommon in ANZ and three quarters die in hospital. However, their frequency varies markedly across institutions and may be affected by the presence of RRS. Where reported, the long-term outcomes survivors appear to have acceptable neurological outcomes. PMID- 26865244 TI - Cortical bone histomorphology of known-age skeletons from the Kirsten collection, Stellenbosch university, South Africa. AB - OBJECTIVES: Normal human bone tissue changes predictably as adults get older, but substantial variability in pattern and pace remains unexplained. Information is needed regarding the characteristics of histological variables across diverse human populations. METHODS: Undecalcified thin sections from mid-thoracic ribs of 213 skeletons (138 M, 75 F, 17-82 years, mean age 48 years), are used to explore the efficacy of an established age-at-death estimation method and methodological approach (Cho et al.: J Forensic Sci 47 (2002) 12-18) and expand on it. The ribs are an age-balanced sample taken from skeletonized cadavers collected from 1967 to 1999 in South Africa, each with recorded sex, age, cause of death and government-defined population group (129 "Colored," 49 "Black," 35 "White"). RESULTS: The Ethnicity Unknown equation performs better than those developed for European-Americans and African-Americans, in terms of accuracy and bias. A new equation based solely on the study sample does not improve accuracy. Osteon population densities (OPD) show predicted values, yet secondary osteon areas (On.Ar) are smaller than expected for non-Black subgroups. Relative cortical area (Ct.Ar/Tt.Ar) is low among non-Whites. CONCLUSIONS: Results from this highly diverse sample show that population-specific equations do not increase estimate precision. While within the published range of error for the method (+/-24.44 years), results demonstrate a systematic under-aging of young adults and over aging of older adults. The regression approach is inappropriate. The field needs fresh approaches to statistical treatment and to factors behind cortical bone remodeling. PMID- 26865246 TI - Self-sacrifice Template Formation of Hollow Hetero-Ni7S6/Co3S4 Nanoboxes with Intriguing Pseudo-capacitance for High-performance Electrochemical Capacitors. AB - Herein, we report a simple yet efficient self-sacrifice template protocol to smartly fabricate hollow hetero-Ni7S6/Co3S4 nanoboxes (Ni-Co-S NBs). Uniform nickel cobalt carbonate nanocubes are first synthesized as the precursor via solvothermal strategy, and subsequently chemically sulfidized into hollow heter Ni-Co-S NBs through anion-exchange process. When evaluated as electrode for electrochemical capacitors (ECs), the resultant hetero-Ni-Co-S NBs visually exhibit attractive pesudo-capacitance in KOH just after continuously cyclic voltammetry (CV) scanning for 100 cycles. New insights into the underlying energy storage mechanism of the hollow hetero-Ni-Co-S electrode, based on physicochemical characterizations and electrochemical evaluation, are first put forward that the electrochemically induced phase transformation gradually occurrs during CV sweep from the hetero-Ni-Co-S to bi-component-active NiOOH and CoOOH, which are the intrinsic charge-storage phases for the appealing Faradaic capacitance (~677 F g(-1) at 4 A g(-1)) of hollow Ni-Co-S NBs at high rates after cycling. When further coupled with negative activated carbon (AC), the AC//hetero Ni-Co-S asymmetric device with extended electrochemical window of 1.5 V demonstrates high specific energy density of ~31 Wh kg(-1). Of significance, we strongly envision that hollow design concept and new findings here hold great promise for enriching synthetic methodologies, and electrochemistry of complex metal sulfides for next-generation ECs. PMID- 26865247 TI - Bioresorbable drug-eluting scaffolds for treatment of vascular disease. AB - INTRODUCTION: Theoretical advantages of fully bioresorbable scaffold (BRS) stem from transient vessel support without rigid caging. Therefore, it could reduce long-term adverse events associated with the presence of foreign materials. AREAS COVERED: This article will provide an overview of: drug-eluting BRS for various applications in the treatment of vascular disease; The mechanisms of active agent release from such scaffolds; currently available drug-eluting BRS and their future applications are also discussed. EXPERT OPINION: The current BRS have been developed in order to achieve optimal vascular patency while providing long-term safety. The clinical efficacy and safety of BRS in coronary treatment have been reported as equal to that of the current metallic drug eluting stents in simple lesions. The application of BRS can potentially be expanded to other vascular beds. The research in bioengineering for the appropriate materials should not only focus on biocompatibility but also should be tailored according to the sites of implantation, which may require different strength and supporting period. The ultimate goal in this field is to develop a biocompatible device that provides equivalent and complementary therapy to other devices, and is able to disappear when the mechanical support and drug delivery are no longer required. PMID- 26865248 TI - HDAC9 exacerbates endothelial injury in cerebral ischaemia/reperfusion injury. AB - Histone deacetylase (HDAC) 9, a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions, which is usually expressed at high levels in the brain and skeletal muscle. Although studies have highlighted the importance of HDAC-mediated epigenetic processes in the development of ischaemic stroke and very recent genome-wide association studies have identified a variant in HDAC9 associated with large-vessel ischemic stroke, the molecular events by which HDAC9 induces cerebral injury keep unclear. In this study, we found that HDAC9 was up-regulated in the ischaemic cerebral hemisphere after cerebral ischaemia/reperfusion (I/R) injury in rats and in vivo gene silencing of HDAC9 by recombinated lentivirus infection in the brain reduced cerebral injury in experimental stroke. We further demonstrated that HDAC9 contributed to oxygen-glucose deprivation-induced brain microvessel endothelial cell dysfunction as demonstrated by the increased inflammatory responses, cellular apoptosis and endothelial cell permeability dysfunction accompanied by reduced expression of tight-junction proteins. We further found that HDAC9 suppressed autophagy, which was associated with endothelial dysfunction. This study for the first time provides direct evidence that HDAC9 contributes to endothelial cell injury and demonstrates that HDAC9 is one of critical components of a signal transduction pathway that links cerebral injury to epigenetic modification in the brain. PMID- 26865250 TI - Moral judgment modulates neural responses to the perception of other's pain: an ERP study. AB - Morality and empathy are both crucial in building human society. Yet the relationship between them has been merely explored. The present study revealed how the morality influenced empathy for pain by comparing the ERPs elicited by pictures showing the targets' in pain primed by different moral information about the targets. We found that when the target was a moral one or a neutral one, the painful pictures elicited significantly larger amplitude in N2 than the non painful pictures, but when the target was an immoral one, the difference between the amplitudes of N2 component elicited by painful and non-painful pictures became insignificant. We proposed that this effect was induced by the decreased affective arousal when observing an immoral person in pain. The reduced neural response towards the immoral one's pain can keep us alert when we face the potentially dangerous people thereby increasing our chance of survival. SLORTEA results showed the source of this difference in N2 localized in the ventral medial prefrontal cortex (vmPFC) and the rostral anterior cingulate cortex (rACC) areas. PMID- 26865249 TI - miRNA Deregulation in Cancer Cells and the Tumor Microenvironment. AB - miRNAs are a key component of the noncoding RNA family. The underlying mechanisms involved in the interplay between the tumor microenvironment and cancer cells involve highly dynamic factors such as hypoxia and cell types such as cancer associated fibroblasts and macrophages. Although miRNA levels are known to be altered in cancer cells, recent evidence suggests a critical role for the tumor microenvironment in regulating miRNA biogenesis, methylation, and transcriptional changes. Here, we discuss the complex protumorigenic symbiotic role between tumor cells, the tumor microenvironment, and miRNA deregulation. SIGNIFICANCE: miRNAs play a central role in cell signaling and homeostasis. In this article, we provide insights into the regulatory mechanisms involved in the deregulation of miRNAs in cancer cells and the tumor microenvironment and discuss therapeutic intervention strategies to overcome this deregulation. PMID- 26865251 TI - A multiple case study of intersectoral public health networks: experiences and benefits of using research. AB - BACKGROUND: Network partnerships between public health and third sector organisations are being used to address the complexities of population level social determinants of health and health equity. An understanding of how these networks use research and knowledge is crucial to effective network design and outcome evaluation. There is, however, a gap in the literature regarding how public health networks use research and knowledge. The purpose of this paper is to report on the qualitative findings from a larger study that explored (1) the experiences of public health networks with using research and knowledge, and (2) the perceived benefits of using research and knowledge. METHODS: A multiple case study approach framed this study. Focus group data were collected from participants through a purposive sample of four public health networks. Data were analyzed using Framework Analysis and Nvivo software supported data management. Each network had the opportunity to participate in data interpretation. RESULTS: All networks used published research studies and other types of knowledge to accomplish their work, although in each network research and knowledge played different but complementary roles. Neither research nor other types of knowledge were privileged, and an approach that blended varied knowledge types was typically used. Network experiences with research and knowledge produced individual and collective benefits. A novel finding was that research and knowledge were both important in shaping network function. CONCLUSIONS: This study shifts the focus in the current literature from public health departments to the community setting where public health collaborates with a broader spectrum of actors to ameliorate health inequities. Both formal research and informal knowledge were found to be important for collaborative public health networks. Examining the benefits of research and knowledge use within public health networks may help us to better understand the relationships among process (the collaborative use of research and knowledge), structure (networks) and outcomes (benefits). PMID- 26865252 TI - Best allogeneic transplantation approach for AML patients in first CR: is delayed unrelated donor bone marrow transplantation better than immediate unrelated cord blood transplantation? PMID- 26865253 TI - Chemotherapy with BCNU in recurrent glioma: Analysis of clinical outcome and side effects in chemotherapy-naive patients. AB - BACKGROUND: To date, standardized strategies for the treatment of recurrent glioma are lacking. Chemotherapy with the alkylating agent BCNU (1,3-bis (2 chloroethyl)-1-nitroso-urea) is a therapeutic option even though its efficacy and safety, particularly the risk of pulmonary fibrosis, remains controversial. To address these issues, we performed a retrospective analysis on clinical outcome and side effects of BCNU-based chemotherapy in recurrent glioma. METHODS: Survival data of 34 mostly chemotherapy-naive glioblastoma patients treated with BCNU at 1st relapse were compared to 29 untreated control patients, employing a multiple Cox regression model which considered known prognostic factors including MGMT promoter hypermethylation. Additionally, medical records of 163 patients treated with BCNU for recurrent glioma WHO grade II to IV were retrospectively evaluated for BCNU-related side effects classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0. RESULTS: In recurrent glioblastoma, multiple regression survival analysis revealed a significant benefit of BCNU-based chemotherapy on survival after relapse (p = 0.02; HR = 0.48; 95% CI = 0.26-0.89) independent of known clinical and molecular prognostic factors. Exploratory analyses suggested that survival benefit was most pronounced in MGMT-hypermethylated, BCNU-treated patients. Moreover, BCNU was well tolerated by 46% of the 163 patients analyzed for side effects; otherwise, predominantly mild side effects occurred (CTCAE I/II; 45%). Severe side effects CTCAE III/IV were observed in 9% of patients including severe hematotoxicity, thromboembolism, intracranial hemorrhage and injection site reaction requiring surgical intervention. One patient presented with a clinically apparent pulmonary fibrosis CTCAE IV requiring temporary mechanical ventilation. CONCLUSION: In this study, BCNU was rarely associated with severe side effects, particularly pulmonary toxicity, and, in case of recurrent glioblastoma, even conferred a favorable outcome. Therefore BCNU appears to be an appropriate alternative to other nitrosoureas although the efficacy against newer drugs needs further evaluation. PMID- 26865255 TI - Influence of pre-harvest calcium, potassium and triazole application on the proteome of apple at harvest. AB - BACKGROUND: Braeburn browning disorder is a storage disease characterised by flesh browning and lens-shaped cavities. The incidence of this postharvest disorder is known to be affected by pre-harvest application of fertilisers and triazole-based fungicides. Recent work has shown that calcium and potassium reduced the incidence of Braeburn browning disorder, while triazoles had the opposite effect. This study addresses the hypothesis of an early proteomic imprint in the apple fruit at harvest induced by the pre-harvest factors applied. If so, this could be used for an early screening of apple fruit at harvest for their postharvest susceptibility to flesh browning. RESULTS: Calcium and triazole had significant effects, while potassium did not. One hundred and thirty protein families were identified, of which 29 were significantly altered after calcium and 63 after triazole treatment. Up-regulation of important antioxidant enzymes was correlated with calcium fertilisation, while triazole induced alterations in the levels of respiration and ethylene biosynthesis related proteins. CONCLUSION: Pre-harvest fertiliser and fungicide application had considerable effects on the apple proteome at harvest. These changes, together with the applied storage conditions will determine whether or not BBD develops. (c) 2016 Society of Chemical Industry. PMID- 26865256 TI - Catalytically driven assembly of trisegmented metallic nanorods and polystyrene tracer particles. AB - Trisegmented Au-Ru-Au and Ru-Au-Ru nanorods catalyze the decomposition of hydrogen peroxide, pumping fluid along their axis as "pullers" and "pushers" respectively. Numerical simulations and experiments with passive tracer particles show that catalytically generated hydrodynamic and electrostatic forces both contribute to pairwise and collective particle assembly. PMID- 26865254 TI - Task sharing for the care of severe mental disorders in a low-income country (TaSCS): study protocol for a randomised, controlled, non-inferiority trial. AB - BACKGROUND: Task sharing mental health care through integration into primary health care (PHC) is advocated as a means of narrowing the treatment gap for mental disorders in low-income countries. However, the effectiveness, acceptability, feasibility and sustainability of this service model for people with a severe mental disorder (SMD) have not been evaluated in a low-income country. METHODS/DESIGN: A randomised, controlled, non-inferiority trial will be carried out in a predominantly rural area of Ethiopia. A sample of 324 people with SMD (diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder or major depressive disorder) with an ongoing need for mental health care will be recruited from 1) participants in a population-based cohort study and 2) people attending a psychiatric nurse-led out-patient clinic. The intervention is a task sharing model of locally delivered mental health care for people with SMD integrated into PHC delivered over 18 months. Participants in the active control arm will receive the established and effective model of specialist mental health care delivered by psychiatric nurses at an out-patient clinic within a centrally located general hospital. The hypothesis is that people with SMD who receive mental health care integrated into PHC will have a non-inferior clinical outcome, defined as a mean symptom score on the Brief Psychiatric Rating Scale, expanded version, of no more than six points higher, compared to participants who receive the psychiatric nurse-led service, after 12 months. The primary outcome is change in symptom severity. Secondary outcomes are functional status, relapse, service use costs, service satisfaction, drop-out and medication adherence, nutritional status, physical health care, quality of care, medication side effects, stigma, adverse events and cost-effectiveness. Sustainability and cost-effectiveness will be further evaluated at 18 months. Randomisation will be stratified by health centre catchment area using random permuted blocks. The outcome assessors and investigators will be masked to allocation status. DISCUSSION: Evidence about the effectiveness of task sharing mental health care for people with SMD in a rural, low-income African country will inform the World Health Organisation's mental health Gap Action Programme to scale-up mental health care globally. TRIAL REGISTRATION: NCT02308956 (ClinicalTrials.gov). Date of registration: 3 December 2014. PMID- 26865257 TI - Herbal medicine use behaviour in Australian adults who experience anxiety: a descriptive study. AB - BACKGROUND: Anxiety disorders are the most prevalent mental health condition in Australia. In addition, there are many people who experience problematic anxiety symptoms who do not receive an anxiety disorder diagnosis but require treatment. As herbal medicine use is popular in Australia, and little is known about how adults experiencing anxiety are using these medicines, this study aimed to identify how Australian adults who experience anxiety are using herbal medicines. METHODS: An online cross-sectional descriptive study was conducted using purposive convenience sampling to recruit Australian adults who have experienced anxiety symptoms and have used herbal medicines (N = 400). Descriptive statistics, chi-square test of contingency, analysis of variance, and simple logistic regression was used to analyse the data. RESULTS: Eighty two percent of participants experienced anxiety symptoms in the previous 12 months, with 47% reporting having previously been diagnosed with an anxiety disorder. In addition, 72.8% had used herbal medicines specifically for anxiety symptoms in their lifetime, while 55.3% had used prescribed pharmaceuticals, with 27.5% having used herbal medicines concurrently with prescribed pharmaceuticals. The Internet and family and friends were the most frequently used sources of information about herbal medicines. Forty eight percent of participants did not disclose their herbal medicine use to their doctor. CONCLUSIONS: Herbal medicines are being used by adults with anxiety and are commonly self-prescribed for anxiety symptoms. Health practitioners who are experts in herbal medicine prescribing are consulted infrequently. In addition, herbal medicine use is often not disclosed to health practitioners. These behaviours are concerning as people may not be receiving the most suitable treatments, and their use of herbal medicines may even be dangerous. It is critical we develop a better understanding of why people are using these medicines, and how we can develop improved health literacy to help with treatment decision making to ensure people receive optimal care. PMID- 26865258 TI - Dyadic Dynamics in a Randomized Weight Loss Intervention. AB - BACKGROUND: Despite health and economic burdens associated with overweight and obesity, long-term weight loss intervention efforts have been largely unsuccessful. Observations that weight status tends to cluster in social groups, and findings showing "ripple" effects of weight change within social clusters, raise questions about the impact of social relationships on weight loss. PURPOSE: Through a reanalysis of data from a randomized weight loss intervention, this study compared dyadic dynamics in intervention participants and in-home partners. METHODS: Over the course of 18 months, data was collected from 201 pairs enrolled in either behavioral weight loss treatment (BWL) or treatment including partners and providing items to facilitate healthy choices at home (BWL + H). Using a dyadic growth curve model, covariance between baseline BMI, BMI change trajectories, and starting BMI and BMI trajectory for both the self and the other were examined. RESULTS: There were strong indicators of dependence in the data. Baseline BMI was positively correlated for both treatment groups. In the BWL + H condition, BMI change trajectories were positively correlated. In the BWL condition, this reversed: Change trajectories were negatively correlated. Additionally, partner BMI and primary participant BMI change were positively correlated, indicating that a heavier partner at baseline related to less weight loss. CONCLUSIONS: Social relationships exert a significant influence on weight loss outcomes. Depending on the intervention group, these influences may help (BWL + H) or hinder (BWL). It may be that home intervention changed social support and interaction in important ways and that these effects could be effectively harnessed to implement more effective interventions (NCT00200330). PMID- 26865259 TI - Pre-Operative Cognitive Functioning and Inflammatory and Neuroendocrine Responses to Cardiac Surgery. AB - BACKGROUND: Cognitive functioning is linked to cardiac mortality and morbidity, but the mechanisms underlying this relationship are unclear. PURPOSE: To examine the relationship between pre-operative cognitive functioning and post-operative inflammatory and neuroendocrine responses in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: One-hundred ninety-three outpatients were screened to assess their cognitive function using the Montreal Cognitive Assessment (MoCA) on average 30 days prior to CABG surgery and provided blood samples for the measurement of interleukin (IL)-6 and C-reactive protein (CRP) and saliva samples for the measurement of diurnal cortisol. Participants were followed-up 4-8 days following surgery for the repeat measurement of IL-6 and CRP and 60 days after surgery for the measurement of diurnal salivary cortisol. RESULTS: Patients with low cognitive function (MoCA < 26) prior to surgery reached higher IL-6 concentrations in the days after surgery (beta = -0.212, p = 0.021) and had greater cortisol output across the day 2 months after surgery (beta = -0.179, p = 0.044). CONCLUSIONS: Low cognitive functioning is associated with a more negative pattern of biological response to surgery, indicative of poorer physical recovery. These pathways may contribute to the links between cognitive function and cardiovascular pathology. PMID- 26865262 TI - Photolytic properties of cobalamins: a theoretical perspective. AB - This Perspective Article highlights recent theoretical developments, and summarizes the current understanding of the photolytic properties of cobalamins from a computational point of view. The primary focus is on two alkyl cobalamins, methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), as well as two non-alkyl cobalamins, cyanocobalamin (CNCbl) and hydroxocobalamin (HOCbl). Photolysis of alkyl cobalamins involves low-lying singlet excited states where photodissociation of the Co-C bond leads to formation of singlet-born alkyl/cob(ii)alamin radical pairs (RPs). Potential energy surfaces (PESs) associated with cobalamin low-lying excited states as functions of both axial bonds, provide the most reliable tool for initial analysis of their photochemical and photophysical properties. Due to the complexity, and size limitations associated with the cobalamins, the primary method for calculating ground state properties is density functional theory (DFT), while time-dependent DFT (TD-DFT) is used for electronically excited states. For alkyl cobalamins, energy pathways on the lowest singlet surface, connecting metal-to-ligand charge transfer (MLCT) and ligand field (LF) minima, can be associated with photo-homolysis of the Co-C bond observed experimentally. Additionally, energy pathways between minima and seams associated with crossing of S1/S0 surfaces, are the most efficient for internal conversion (IC) to the ground state. Depending on the specific cobalamin, such IC may involve simultaneous elongation of both axial bonds (CNCbl), or detachment of axial base followed by corrin ring distortion (MeCbl). The possibility of intersystem crossing, and the formation of triplet RPs is also discussed based on Landau-Zener theory. PMID- 26865261 TI - Toxicities and early outcomes in a phase 1 trial of photodynamic therapy for premalignant and early stage head and neck tumors. AB - OBJECTIVES: Management of early superficial lesions in the head and neck remains complex. We performed a phase 1 trial for high-grade premalignant and early superficial lesions of the head and neck using photodynamic therapy (PDT) with Levulan (ALA). MATERIALS AND METHODS: Thirty-five subjects with high grade dysplasia, carcinoma in situ, or microinvasive (?1.5mm depth) squamous cell carcinoma were enrolled. Cohorts of 3-6 patients were given escalating intraoperative light doses of 50-200J/cm(2) 4-6h after oral administration of 60mg/kg ALA. Light at 629-635nm was delivered in a continuous (unfractionated) or fractionated (two-part) schema. RESULTS: PDT was delivered to 30/35 subjects, with 29 evaluable. There was one death possibly due to the treatment. The regimen was otherwise tolerable, with a 52% rate of grade 3 mucositis which healed within several weeks. Other toxicities were generally grade 1 or 2, including odynophagia (one grade 4), voice alteration (one grade 3), and photosensitivity reactions. One patient developed grade 5 sepsis. With a median follow-up of 42months, 10 patients (34%) developed local recurrence; 4 of these received 50J/cm(2) and two each received 100, 150, and 200J/cm(2). Ten (34%) patients developed recurrence adjacent to the treated field. There was a 69% complete response rate at 3months. CONCLUSIONS: ALA-PDT is well tolerated. Maximum Tolerated Dose appears to be higher than the highest dose used in this study. Longer followup is required to analyze effect of light dose on local recurrence. High marginal recurrence rates suggest use of larger treatment fields. PMID- 26865264 TI - Editorial: Gun Violence--Risk, Consequences, and Prevention. PMID- 26865263 TI - New insights into the mechanism of substrates trafficking in Glyoxylate/Hydroxypyruvate reductases. AB - Glyoxylate accumulation within cells is highly toxic. In humans, it is associated with hyperoxaluria type 2 (PH2) leading to renal failure. The glyoxylate content within cells is regulated by the NADPH/NADH dependent glyoxylate/hydroxypyruvate reductases (GRHPR). These are highly conserved enzymes with a dual activity as they are able to reduce glyoxylate to glycolate and to convert hydroxypyruvate into D-glycerate. Despite the determination of high-resolution X-ray structures, the substrate recognition mode of this class of enzymes remains unclear. We determined the structure at 2.0 A resolution of a thermostable GRHPR from Archaea as a ternary complex in the presence of D-glycerate and NADPH. This shows a binding mode conserved between human and archeal enzymes. We also determined the first structure of GRHPR in presence of glyoxylate at 1.40 A resolution. This revealed the pivotal role of Leu53 and Trp138 in substrate trafficking. These residues act as gatekeepers at the entrance of a tunnel connecting the active site to protein surface. Taken together, these results allowed us to propose a general model for GRHPR mode of action. PMID- 26865266 TI - Ancient Disease, Modern Epidemiology: A Century of Progress in Understanding and Fighting Tuberculosis. AB - A century's worth of efforts to better understand the epidemiology of tuberculosis (TB) and to develop new vaccines, drugs, preventive interventions, and case-finding approaches have provided important insights and helped to advance the field of epidemiology as a whole. Wade Hampton Frost developed methods for cohort analysis that formed the early basis for adjustment of confounding variables. The streptomycin trial in the United Kingdom in the 1940s introduced random allocation for participants to either the treatment or control group, ensuring blinded treatment assignment and comparable treatment groups, which is now a key element in randomized clinical trials. Research into the bacille Calmette-Guerin vaccine demonstrated the importance of comparative analyses, potential difficulties in generalizability to populations not under study, and the role of meta-analysis for discrepant data-approaches now strongly recommended prior to implementing any novel public health intervention. George Comstock's work on preventive therapy for TB demonstrated the use of epidemiologic methods to evaluate interventions on a population level. Finally, studies from the Consortium to Respond Effectively to the AIDS/TB Epidemic focused on the evaluation of real-world effectiveness and of targeting of high risk subpopulations. In this article, we discuss how TB research in each of these domains has helped to advance epidemiologic thinking and methodology over the past 100 years. PMID- 26865265 TI - Sex-Based Differences in Rates, Causes, and Predictors of Death Among Injection Drug Users in Vancouver, Canada. AB - In the present study, we sought to identify rates, causes, and predictors of death among male and female injection drug users (IDUs) in Vancouver, British Columbia, Canada, during a period of expanded public health interventions. Data from prospective cohorts of IDUs in Vancouver were linked to the provincial database of vital statistics to ascertain rates and causes of death between 1996 and 2011. Mortality rates were analyzed using Poisson regression and indirect standardization. Predictors of mortality were identified using multivariable Cox regression models stratified by sex. Among the 2,317 participants, 794 (34.3%) of whom were women, there were 483 deaths during follow-up, with a rate of 32.1 (95% confidence interval (CI): 29.3, 35.0) deaths per 1,000 person-years. Standardized mortality ratios were 7.28 (95% CI: 6.50, 8.14) for men and 15.56 (95% CI: 13.31, 18.07) for women. During the study period, mortality rates related to infection with human immunodeficiency virus (HIV) declined among men but remained stable among women. In multivariable analyses, HIV seropositivity was independently associated with mortality in both sexes (all P < 0.05). The excess mortality burden among IDUs in our cohorts was primarily attributable to HIV infection; compared with men, women remained at higher risk of HIV-related mortality, indicating a need for sex-specific interventions to reduce mortality among female IDUs in this setting. PMID- 26865267 TI - High Content Imaging of Early Morphological Signatures Predicts Long Term Mineralization Capacity of Human Mesenchymal Stem Cells upon Osteogenic Induction. AB - Human bone marrow-derived multipotent mesenchymal stromal cells, often referred to as mesenchymal stem cells (MSCs), represent an attractive cell source for many regenerative medicine applications due to their potential for multi-lineage differentiation, immunomodulation, and paracrine factor secretion. A major complication for current MSC-based therapies is the lack of well-defined characterization methods that can robustly predict how they will perform in a particular in vitro or in vivo setting. Significant advances have been made with identifying molecular markers of MSC quality and potency using multivariate genomic and proteomic approaches, and more recently with advanced techniques incorporating high content imaging to assess high-dimensional single cell morphological data. We sought to expand upon current methods of high dimensional morphological analysis by investigating whether short term cell and nuclear morphological profiles of MSCs from multiple donors (at multiple passages) correlated with long term mineralization upon osteogenic induction. Using the combined power of automated high content imaging followed by automated image analysis, we demonstrated that MSC morphology after 3 days was highly correlated with 35 day mineralization and comparable to other methods of MSC osteogenesis assessment (such as alkaline phosphatase activity). We then expanded on this initial morphological characterization and identified morphological features that were highly predictive of mineralization capacities (>90% accuracy) of MSCs from additional donors and different manufacturing techniques using linear discriminant analysis. Together, this work thoroughly demonstrates the predictive power of MSC morphology for mineralization capacity and motivates further studies into MSC morphology as a predictive marker for additional in vitro and in vivo responses. PMID- 26865269 TI - A novel Flt3-deficient HIS mouse model with selective enhancement of human DC development. AB - Humanized mice harboring human immune systems (HIS) represent a platform to study immune responses against pathogens and to screen vaccine candidates and novel immunotherapeutics. Innate and adaptive immune responses are suboptimal in HIS mice, possibly due to poor reconstitution of human antigen-presenting cells, including dendritic cells (DCs). DC homeostasis is regulated by cytokine availability, and Flt3-ligand (Flt3L) is one factor that conditions this process. Mouse myelopoiesis is essentially normal in most current HIS models. As such, developing mouse myeloid cells may limit human DC reconstitution by reducing available Flt3L and by cellular competition for specific "niches." To address these issues, we created a novel HIS model that compromises host myeloid cell development via deficiency in the receptor tyrosine kinase Flk2/Flt3. In Balb/c Rag2(-/-) Il2rg(-/-) Flt3(-/-) (BRGF) recipients, human conventional DCs and plasmacytoid DCs develop from hCD34(+) precursors and can be specifically boosted with exogenous Flt3L. Human DCs that develop in this context normally respond to TLR stimulation, and improved human DC homeostasis is associated with increased numbers of human NK and T cells. This new HIS-DC model should provide a means to dissect human DC differentiation and represents a novel platform to screen immune adjuvants and DC targeting therapies. PMID- 26865268 TI - LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells. AB - Diabetic neuropathy (DNP) is a frequent chronic complication of diabetes mellitus with potentially life-threatening outcomes. High glucose and elevated free fatty acids (FFAs) have been recently recognized as major causes of nervous system damage in diabetes. Our previous study has indicated extracellular stimuli, such as high glucose and/or FFA stress, may activate the p38 mitogen-activated protein kinase (MAPK) signaling pathway and induce a p38 MAPK-dependent sensitization of the P2X7 receptor and release of inflammatory factors in PC12 cells, while the mechanisms underlying remain to be elucidated. Long noncoding RNAs (lncRNAs) play important roles in diverse biological processes, including activation of a series of pathway signalings. Here, we showed combined high D-glucose and FFAs (HGHF) induced an increment of lncRNA-NONRATT021972 (NONCODE ID, nc021972) in PC12 cells. Nc021972 small interference RNA (siRNA) alleviated HGHF-induced activation of p38 MAPK, expression of the P2X7 receptor, and [Ca(2+)]i increment upon P2X7 receptor activation. Further experiments showed that there existed a crosstalk between nc021972 and the p38 MAPK signaling pathway. Inhibition of p38 MAPK signaling decreased nc021972-induced expression of the P2X7 receptor and [Ca(2+)]i increment upon P2X7 receptor activation. Also, nc021972 siRNA inhibited HGHF-induced PC12 release of TNF-alpha and IL-6 and rescued decreased cell viability mediated by the P2X7 receptor. Therefore, inhibition of nc021972 may serve as a novel therapeutic strategy for diabetes complicated with nervous inflammatory diseases. PMID- 26865270 TI - Tumor cell-derived secretory factor downregulates Semaphorin-3a in osteoblasts by activating mammalian target of rapamycin pathway. AB - We found that conditioned medium derived from Lewis Lung Carcinoma cells down regulated Semaphorin3a (Sema3a) mRNA expression and increased the activity of mammalian target of rapamycin complex 1 (mTORC1) in osteoblast-like MC3T3-E1 cells. Furthermore, mTORC1 inhibition with rapamycin counteracted the effect of conditioned media on Sema3a mRNA expression. These results suggest that tumor cells decrease Sema3a mRNA expression in osteoblast in an mTORC1-dependent manner. PMID- 26865272 TI - Distribution of toxic chemicals in particles of various sizes from mainstream cigarette smoke. AB - To accurately estimate the risk of inhaling cigarette smoke containing toxic chemicals, it is important that the distribution of these chemicals is accurately measured in cigarette smoke aerosol particles of various sizes. In this study, a single-channel smoking machine was directly coupled to an electrical low-pressure impactor. The particles of mainstream cigarette smoke were collected using 12 polyester films, and the particulate matter (PM) was characterized. Nicotine, tobacco-specific N-nitrosamines (TSNAs, including NNN, NAT, NAB, and NNK), polycyclic aromatic hydrocarbons (PAHs, including benzo(a)pyrene (BaP), benzo(a)anthracene, and chrysene), and heavy metals (including Cr, As, Cd, and Pb) present in the particles of different sizes were analyzed by GC, HPLC-MS/MS, GC/MS, or ICP-MS, respectively. The results demonstrated that the nicotine, TSNAs, PAHs, and heavy metals in mainstream cigarette smoke were dispersed over a particle size ranging from 0.1 MUm to 2.0 MUm, and the concentration of these toxic chemicals initially increased and then decreased the particle size grew. The distribution of nicotine was uniform for the PM in the size ranges of less than 0.1 MUm, 0.1-1.0 MUm, and 1.0-2.0 MUm, TSNAs and heavy metals in particles of less 0.1 MUm were more abundant, and PAHs in fine particles were also more abundant. PMID- 26865273 TI - Analysis of a Rapid Evolutionary Radiation Using Ultraconserved Elements: Evidence for a Bias in Some Multispecies Coalescent Methods. AB - Rapid evolutionary radiations are expected to require large amounts of sequence data to resolve. To resolve these types of relationships many systematists believe that it will be necessary to collect data by next-generation sequencing (NGS) and use multispecies coalescent ("species tree") methods. Ultraconserved element (UCE) sequence capture is becoming a popular method to leverage the high throughput of NGS to address problems in vertebrate phylogenetics. Here we examine the performance of UCE data for gallopheasants (true pheasants and allies), a clade that underwent a rapid radiation 10-15 Ma. Relationships among gallopheasant genera have been difficult to establish. We used this rapid radiation to assess the performance of species tree methods, using ~600 kilobases of DNA sequence data from ~1500 UCEs. We also integrated information from traditional markers (nuclear intron data from 15 loci and three mitochondrial gene regions). Species tree methods exhibited troubling behavior. Two methods [Maximum Pseudolikelihood for Estimating Species Trees (MP-EST) and Accurate Species TRee ALgorithm (ASTRAL)] appeared to perform optimally when the set of input gene trees was limited to the most variable UCEs, though ASTRAL appeared to be more robust than MP-EST to input trees generated using less variable UCEs. In contrast, the rooted triplet consensus method implemented in Triplec performed better when the largest set of input gene trees was used. We also found that all three species tree methods exhibited a surprising degree of dependence on the program used to estimate input gene trees, suggesting that the details of likelihood calculations (e.g., numerical optimization) are important for loci with limited phylogenetic information. As an alternative to summary species tree methods we explored the performance of SuperMatrix Rooted Triple - Maximum Likelihood (SMRT-ML), a concatenation method that is consistent even when gene trees exhibit topological differences due to the multispecies coalescent. We found that SMRT-ML performed well for UCE data. Our results suggest that UCE data have excellent prospects for the resolution of difficult evolutionary radiations, though specific attention may need to be given to the details of the methods used to estimate species trees. PMID- 26865271 TI - Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11alpha by Src kinase regulates the trafficking of amyloid precursor protein. AB - Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate beta amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease. PMID- 26865274 TI - Inferring Bounded Evolution in Phenotypic Characters from Phylogenetic Comparative Data. AB - Our understanding of phenotypic evolution over macroevolutionary timescales largely relies on the use of stochastic models for the evolution of continuous traits over phylogenies. The two most widely used models, Brownian motion and the Ornstein-Uhlenbeck (OU) process, differ in that the latter includes constraints on the variance that a trait can attain in a clade. The OU model explicitly models adaptive evolution toward a trait optimum and has thus been widely used to demonstrate the existence of stabilizing selection on a trait. Here we introduce a new model for the evolution of continuous characters on phylogenies: Brownian motion between two reflective bounds, or Bounded Brownian Motion (BBM). This process also models evolutionary constraints, but of a very different kind. We provide analytical expressions for the likelihood of BBM and present a method to calculate the likelihood numerically, as well as the associated R code. Numerical simulations show that BBM achieves good performance: parameter estimation is generally accurate but more importantly BBM can be very easily discriminated from both BM and OU. We then analyze climatic niche evolution in diprotodonts and find that BBM best fits this empirical data set, suggesting that the climatic niches of diprotodonts are bounded by the climate available in Australia and the neighboring islands but probably evolved with little additional constraints. We conclude that BBM is a valuable addition to the macroevolutionary toolbox, which should enable researchers to elucidate whether the phenotypic traits they study are evolving under hard constraints between bounds. PMID- 26865275 TI - Bats (Chiroptera: Noctilionoidea) Challenge a Recent Origin of Extant Neotropical Diversity. AB - The mechanisms underlying the high extant biodiversity in the Neotropics have been controversial since the 19th century. Support for the influence of period specific changes on diversification often rests on detecting more speciation events during a particular period. The timing of speciation events may reflect the influence of incomplete taxon sampling, protracted speciation, and null processes of lineage accumulation. Here we assess the influence of these factors on the timing of speciation with new multilocus data for New World noctilionoid bats (Chiroptera: Noctilionoidea). Biogeographic analyses revealed the importance of the Neotropics in noctilionoid diversification, and the critical role of dispersal. We detected no shift in speciation rate associated with the Quaternary or pre-Quaternary periods, and instead found an increase in speciation linked to the evolution of the subfamily Stenodermatinae (~18 Ma). Simulations modeling constant speciation and extinction rates for the phylogeny systematically showed more speciation events in the Quaternary. Since recording more divergence events in the Quaternary can result from lineage accumulation, the age of extant sister species cannot be interpreted as supporting higher speciation rates during this period. Instead, analyzing the factors that influence speciation requires modeling lineage-specific traits and environmental, spatial, and ecological drivers of speciation. PMID- 26865278 TI - Shared clonal cytogenetic abnormalities in aberrant mast cells and leukemic myeloid blasts detected by single nucleotide polymorphism microarray-based whole genome scanning. AB - Systemic mastocytosis (SM) is characterized by a clonal proliferation of aberrant mast cells within extracutaneous sites. In a subset of SM cases, a second associated hematologic non-mast cell disease (AHNMD) is also present, usually of myeloid origin. Polymerase chain reaction and targeted fluorescence in situ hybridization studies have provided evidence that, in at least some cases, the aberrant mast cells are related clonally to the neoplastic cells of the AHNMD. In this work, a single nucleotide polymorphism microarray (SNP-A) was used to characterize the cytogenetics of the aberrant mast cells from a patient with acute myeloid leukemia and concomitant mast cell leukemia associated with a KIT D816A mutation. The results demonstrate the presence of shared cytogenetic abnormalities between the mast cells and myeloid blasts, as well as additional abnormalities within mast cells (copy-neutral loss of heterozygosity) not detectable by routine karyotypic analysis. To our knowledge, this work represents the first application of SNP-A whole-genome scanning to the detection of shared cytogenetic abnormalities between the two components of a case of SM-AHNMD. The findings provide additional evidence of a frequent clonal link between aberrant mast cells and cells of myeloid AHNMDs, and also highlight the importance of direct sequencing for identifying uncommon activating KIT mutations. PMID- 26865277 TI - Integrated genomic profiling identifies microRNA-92a regulation of IQGAP2 in locally advanced rectal cancer. AB - Locally advanced rectal cancer (LARC) is treated with chemoradiation prior to surgical excision, leaving residual tumors altered or completely absent. Integrating layers of genomic profiling might identify regulatory pathways relevant to rectal tumorigenesis and inform therapeutic decisions and further research. We utilized formalin-fixed, paraffin-embedded pre-treatment LARC biopsies (n=138) and compared copy number, mRNA, and miRNA expression with matched normal rectal mucosa. An integrative model was used to predict regulatory interactions to explain gene expression changes. These predictions were evaluated in vitro using multiple colorectal cancer cell lines. The Cancer Genome Atlas (TCGA) was also used as an external cohort to validate our genomic profiling and predictions. We found differentially expressed mRNAs and miRNAs that characterize LARC. Our integrative model predicted the upregulation of miR-92a, miR-182, and miR-221 expression to be associated with downregulation of their target genes after adjusting for the effect of copy number alterations. Cell line studies using miR-92a mimics and inhibitors demonstrate that miR-92a expression regulates IQGAP2 expression. We show that endogenous miR-92a expression is inversely associated with endogenous KLF4 expression in multiple cell lines, and that this relationship is also present in rectal cancers of TCGA. Our integrative model predicted regulators of gene expression change in LARC using pre-treatment FFPE tissues. Our methodology implicated multiple regulatory interactions, some of which are corroborated by independent lines of study, while others indicate new opportunities for investigation. PMID- 26865279 TI - Better approach needed to detect and treat military personnel with adverse effects from mefloquine. PMID- 26865280 TI - Expanding Our Understanding of Age-Related Mortality After Gastric Bypass Surgery. PMID- 26865281 TI - Oxytocin as a protective agent in cisplatin-induced ototoxicity. AB - PURPOSE: Cisplatin is a potent chemotherapeutic drug with serious side effects such as ototoxicity which is characterized by irreversible, bilateral, progressive sensorineural hearing loss. Oxytocin, which is a well-known hormone secreting during pregnancy, has antioxidant and antiinflammatory effect. Our study aims to test and compare the effect of intratympanic (IT) and intraperitoneal (IP) oxytocin on cisplatin ototoxicity with DPOAE. METHODS: A total of 24 Wistar albino rats were randomly divided into four groups: Group 1 received 0.1-0.3 ml IT saline + IP saline solutions for 4 days (n = 6), Group 2 received cumulative dose of 20 mg/kg IP cisplatin divided into two equal doses in first and second days of experiment + 0.1-0.3 ml IT saline for 4 days, Group 3 received same dose of cisplatin as Group 2 + 0.1-0.3 ml IT oxytocin for 4 days, and Group 4 received same dose of cisplatin as Groups 2 and 3 + IP oxytocin with dose of 1 mg/kg. DPOAE was performed prior to procedure and at the end of the experiment on day 5. RESULTS: Group 2 showed severe ototoxic effect of cisplatin according to DPOAE result (p < 0.05). When compared with Group 2, DPOAE amplitude reductions were smaller in Group 3 (3.2, 3.8, 4.5, 6.3 and 7.6 kHz) (p < 0.05) and Group 4 which is statistically significant in 5.4, 6.3 and 7.6 kHz (p < 0.05). When Group 3 and Group 4 were compared, reductions were smaller in 2.7 and 3.2 kHz in Group 3 (p < 0.05). CONCLUSION: In this study, we showed the protective effect of IT and IP oxytocin on cisplatin ototoxicity. We suggest oxytocin in cisplatin ototoxicity, especially via IT route even with high-dose cisplatin. PMID- 26865282 TI - Building an Inclusive Culture in the Chemistry Department at Imperial College. AB - One of the main aims of any department is to appoint the very best chemists and to support them to reach their full potential. Success in this aim cannot look like a male to female ratio of professors of 20:1. In this Guest Editorial, T. Welton, Dean of the Faculty of Natural Sciences at Imperial College London, describes the processes introduced that led to the Chemistry Department at Imperial achieving a gold Athena SWAN award. PMID- 26865284 TI - Coronary or thoracic artery calcium score in provoked and unprovoked pulmonary embolism: a case-control study. AB - Essentials Patients with unprovoked pulmonary embolism (PE) are at increased risk of arterial thromboembolism. Coronary and thoracic aorta calcium were evaluated in patients with and without (unprovoked) PE. No association was found between (unprovoked) PE and coronary or aortic calcification. Assessment of both calcium scores on computed tomography pulmonary angiography was highly reproducible. SUMMARY: Objective To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presence and extent of coronary artery calcium (CAC) and thoracic aorta calcium (TAC). Methods CAC and TAC derived from computed tomography pulmonary angiography of 100 patients with PE were compared to that of 100 patients in whom PE was ruled out. Results Intraobserver and interobserver agreements for both TAC and CAC were excellent (intraclass correlation > 0.95 for both). In patients with PE vs. patients without PE, no significant differences were found in the presence of CAC or TAC (CAC 64% vs. 67%, odds ratio [OR] 1.0, 95% confidence interval [CI] 0.67-1.6; TAC 46% vs. 59%, OR 1.2, 95% CI 0.80-2.1). Mean CAC and TAC scores were significantly lower in patients with PE than in patients without PE (CAC 3.4 vs. 4.9, absolute difference 1.5, 95% CI 0.2-2.8; TAC 1.1 vs. 1.8, absolute difference 0.9, 95% CI 0.2-1.2). No significant differences were found in the presence of CAC or TAC or in mean CAC and TAC scores between patients with unprovoked PE vs. patients with provoked PE, or between patients with unprovoked PE vs. no PE. Conclusion No significant differences were found between the extent of CAC and TAC in patients with unprovoked PE compared to those with provoked PE or without PE. The observed difference in the extend of CAC and TAC between patients with and without PE was dependent on prevalent cardiovascular risk factors. PMID- 26865285 TI - Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-transplant CDT monitoring for alcohol relapse assessment - a retrospective study. AB - Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post-LT long-term observation is challenging, and biomarkers as carbohydrate-deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow-up was 73 months (0-213). One- and five-year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post-transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single-center analysis showed good post-transplant long term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post-LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse. PMID- 26865283 TI - Safety Concerns Surrounding Quinolone Use in Children. AB - Fluoroquinolones are highly effective antibiotics with many desirable pharmacokinetic and pharmacodynamic properties including high bioavailability, large volume of distribution, and a broad spectrum of antimicrobial activity. Despite their attractive profile as anti-infective agents, their use in children is limited, primarily due to safety concerns. In this review we highlight the pharmacological properties of fluoroquinolones and describe their current use in pediatrics. In addition, we provide a comprehensive assessment of the safety data associated with fluoroquinolone use in children. Although permanent or destructive arthropathy remains a significant concern, currently available data demonstrate that arthralgia and arthropathy are relatively uncommon in children and resolve following cessation of fluoroquinolone exposure without resulting in long-term sequelae. The concern for safety and risk of adverse events associated with pediatric fluoroquinolone use is likely driving the limited prescribing of this drug class in pediatrics. However, in adults, fluoroquinolones are the most commonly prescribed broad-spectrum antibiotics, resulting in the development of drug-resistant bacteria that can be challenging to treat effectively. The consequence of misuse and overuse of fluoroquinolones leading to drug resistance is a greater, but frequently overlooked, safety concern that applies to both children and adults and one that should be considered at the point of prescribing. PMID- 26865286 TI - Effect of alpha-Hederin on IL-2 and IL-17 mRNA and miRNA-133a Levels in Lungs of Ovalbumin-Sensitized Male Rats. AB - alpha-hederin, a saponin that is a major constituent of English Ivy (Hedera helix) is effective in the treatment of asthma. In the present study, the effect of alpha-hederin on lung tissue pathology and the levels of the inflammatory mediators; IL-2 mRNA, IL-17 mRNA, and MicroRNAs (miRNA)-133a was evaluated in a rat ovalbumin (OVA)-sensitized model of asthma. Rats were divided randomly into control (C), OVA-sensitized (S), OVA-sensitized pretreated with the antioxidant, thymoquinone (3 mg/kg, S + TQ) or OVA-sensitized pretreated with alpha-hederin (0.02 mg/kg, S + AH) groups. Levels of IL-2 and IL-17 mRNA were higher in the OVA sensitized group than controls while the level of miRNA-133a gene expression was lower. IL-2 mRNA and miRNA-133a gene expression in the S + TQ group was higher than in the control and OVA-sensitized groups while the level of IL-17 mRNA in the S + TQ group was lower than in the OVA-sensitized group. Pretreatment with alpha-hederin decreased IL-17 mRNA levels and increased miRNA-133a gene expression compared with OVA-sensitized animals. All pathological changes in pretreated groups were lower than the OVA-sensitized group. These results showed a beneficial effect of alpha-hederin in OVA-sensitized rats, suggesting that alpha-hederin affects the IL-2 and IL-17 secretion pathways, altering miRNA-133a expression. PMID- 26865287 TI - Companion Versus Comparison: Examining Seeking Social Companionship or Social Comparison as Characteristics That Differentiate Happy and Unhappy People. AB - Which friend do you want to spend time with-a happy friend who performs better than you or an unhappy friend who performs worse than you? The present research demonstrates that in such conflicting situations, when the desires for companionship and comparison are pitted against each other, one's level of happiness plays an important role in one's choice. Using hypothetical scenarios, we found that compared with unhappy people, happy people expected that spending time with a happy, superior friend would be more pleasant than spending time with an unhappy, inferior friend (Studies 1B through 2) and were more willing to socialize with a happy, superior friend than with an unhappy, inferior friend (Studies 1B through 2). Moreover, this pattern was not explained by self-esteem (Study 2) or the similarity-attraction hypothesis (Study 3). The present findings suggest that happy people place more value on companionship than on comparison. PMID- 26865288 TI - The Costs of Suppressing Negative Emotions and Amplifying Positive Emotions During Parental Caregiving. AB - How do parents feel when they regulate their emotional expressions in ways that are incongruent with their genuine feelings? In an experimental study, parents reported experiencing lower authenticity, emotional well-being, relationship quality, and responsiveness to their children's needs when they recalled caregiving experiences in which they suppressed negative emotions and amplified positive emotions, relative to a control condition. In a 10-day daily experience study, parents tended to use both regulation strategies simultaneously. In addition, assessing their unique effects indicated that positive emotion amplification, but not negative emotion suppression, had an indirect effect on parental outcomes via authenticity, with negative emotion suppression no longer being costly. This indirect effect was dampened when accounting for care difficulty. In both studies, effects were independent of a child's mood. The current results suggest that parents' attempts to suppress negative and amplify positive emotions during child care can detract from their well-being and high quality parent-child bonds. PMID- 26865289 TI - Third-Party Cooperation: How Reducing Material Involvement Enhances Contributions to the Public Good. AB - Decisions to cooperate are often delegated to a third party. We examined whether cooperation differs when decisions are made for a third party compared with ourselves and specified which motives are important for third-party cooperation. Participants played multiple rounds of a public goods game (PGG). In Study 1, we varied personal involvement from high to low; participants played for themselves (Self), for themselves and a third party (Shared), and solely for a third party (Third Party). Participants contributed most when personal involvement was lowest (i.e., Third Party) and least when personal involvement was high (i.e., Self). Study 2 explored if social motives underlie third-party cooperation by comparing cooperation with social (human) and non-social (computer) group members. Reducing personal involvement in the PGG (i.e., Third Party) increased cooperation in social contexts compared with non-social contexts, indicating enhanced collective interest. Increased cooperation for a third party may result from taking the other's perspective, thereby increasing social norm preferences. PMID- 26865290 TI - Changing US Attributes After CS-US Pairings Changes CS-Attribute-Assessments: Evidence for CS-US Associations in Attribute Conditioning. AB - Attribute Conditioning (AC) refers to people's changed assessments of stimuli's (CSs) attributes due to repeated pairing with stimuli (USs) possessing these attributes; for example, when an athletic person (US) is paired with a neutral person (CS), the neutral person is judged to be more athletic after the pairing. We hypothesize that this AC effect is due to CSs' associations with USs rather than direct associations with attributes. Three experiments test this hypothesis by changing US attributes after CS-US pairings. Experiments 1 and 2 conditioned athleticism by pairing neutral men (CSs) with athletic and non-athletic USs. Post conditioning, USs' athleticism was reversed, which systematically influenced participants' assessment of CS athleticism. Experiment 3 conditioned athleticism and changed USs' musicality after CS-US pairings. This post-conditioning change affected musicality assessments of CSs but did not influence athleticism assessments. The results indicate that AC effects are based on an associative CS US-attribute structure. PMID- 26865291 TI - Narcissists of a Feather Flock Together: Narcissism and the Similarity of Friends. AB - Who is willing to expose himself or herself to narcissists on a long-term basis? Studies that address the interactions of narcissists focus mainly on their interactions with strangers. Hence, the aim of the present study was to investigate the extent to which two best friends' similarity in narcissism would influence their similarities in other personality profiles. A total of 290 best friends' dyads filled out measurements of the whole Dark Triad as well as the Big Five. For each personality domain, profile similarity and its dependence on the similarity in the Dark Triad were determined. Results showed that the friends' similarity in narcissism significantly predicted similarity in all Big Five domains. For the general Big Five similarity as well as extraversion, the effect of narcissism similarity was stronger for male than female or mixed friends. Similarity in psychopathy and Machiavellianism significantly predicted all domains except for openness and extraversion, respectively. PMID- 26865292 TI - The Scope of Our Affective Influences: When and How Naturally Occurring Positive, Negative, and Neutral Affects Alter Judgment. AB - To determine how naturally arising affect alters judgment, we examined whether (a) affective states exert a specific, rather than a general, influence on valenced-specific judgments; (b) neutral affect is associated with increased neutral judgments, independent of positive, negative, and ambivalent affects, and whether neutral judgments are associated with behavioral disengagement; and (c) the informational value of naturally arising states may be difficult to alter via salience and relevance manipulations. The results support several conclusions: (a) Affective states exerted a judgment-specific effect-positive affect was most strongly associated with positive judgments, negative affect with negative judgments, and neutral affect with neutral judgments. (b) Neutral affect influenced judgments, taking into account positive, negative, and ambivalent affects; and neutral judgments predicted behavioral disengagement. (c) With the exception of negative affect, naturally arising affective states typically influenced judgments regardless of their salience and relevance. PMID- 26865293 TI - Costs of Care for Hospitalization for Pemphigus in the United States. AB - IMPORTANCE: Pemphigus is an autoimmune blistering disorder associated with significant morbidity and mortality. However, little is known about the inpatient burden of pemphigus. OBJECTIVE: To determine the incidence of and risk factors for hospitalization with pemphigus and cost of care. DESIGN, SETTING, AND PARTICIPANTS: The 2002-2012 Nationwide Inpatient Sample provided by the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality was analyzed. A total of 87 039 711 children and adults (mean [SD] age, 57.7 [0.98] years for those with a primary diagnosis of pemphigus; 70.6 [0.32] years for those with a secondary diagnosis of pemphigus; and 47.9 [0.19] years for those without a diagnosis of pemphigus) were studied. Data analysis was performed from June 1 to August 30, 2015. MAIN OUTCOMES AND MEASURES: Hospitalization rates, length of stay, and cost of care. RESULTS: There were 1185 and 5221 patients admitted with a primary or secondary diagnosis of pemphigus, respectively; when factoring in weights that generalize the sample to the entire hospitalized US cohort, these admissions represented weighted frequencies of 5647 and 24 880, respectively. In multivariable logistic regression models with stepwise selection, increasing age (adjusted odds ratios [95% CIs]: 18-39 years: 5.53 [4.28-7.14], P < .001; 40-59 years: 10.98 [8.46-14.24], P < .001; 60-79 years: 7.54 [5.75-9.89], P < .001; >=80 years: 7.57 [5.71-10.04], P < .001), female sex (1.10 [1.01-1.20], P = .047), nonwhite race/ethnicity (black: 1.94 [1.75-2.14], P < .001; Hispanic: 4.10 [3.74-4.48], P < .001; Asian: 3.16 [2.68 3.73], P < .001; Native American: 2.11 [1.45-3.08], P < .001), lower household income (quartile 2: 1.19 [1.07-1.32], P < .001), being insured with Medicare (1.56 [1.41-1.74], P < .001) or Medicaid (1.55 [1.39-1.73], P < .001), number of chronic conditions (2-5: 2.36 [2.10-2.65], P < .001; >=6: 1.47 [1.29-1.69], P < .001), hospital location in a metropolitan area (not metropolitan or micropolitan: 0.60 [0.49-0.72], P < .001), and summer season (1.12 [1.02-1.23], P = .02) were all associated with hospitalization for pemphigus. The total inflation-adjusted cost of care for patients with a primary inpatient diagnosis of pemphigus was $74 466 305, with a mean (SD) annual cost of $14 520.93 ($913.22). The inflation-adjusted cost of care for patients with a primary diagnosis of pemphigus increased significantly from 2002 to 2012 (analysis of variance, P < .001). In particular, length of stay was higher in racial/ethnic minorities compared with whites (survey linear regression, log beta [95% CI]: black: 0.076 [0.075-0.076]; Hispanic: 0.021 [0.021-0.022]; Asian: 0.037 [0.036 0.039]; Native American: 0.010 [0.0076-0.013]), lower quartile household income (quartile 1: 0.024 [0.023-0.024]; quartile 2: 0.0029 [0.0022-0.0035]), and those without private insurance (Medicare: 0.12 [0.12-0.12]; Medicaid: 0.082 [0.081 0.083]; no charge: 0.051 [0.047-0.055]). CONCLUSIONS AND RELEVANCE: There is a significant inpatient burden for pemphigus in the United States. Moreover, there appear to be racial/ethnic and health care disparities with respect to pemphigus, such that poor, nonwhite, and/or uninsured or underinsured patients have higher odds of hospitalization. PMID- 26865294 TI - Breakfast frequency among adolescents: associations with measures of family functioning. AB - OBJECTIVE: To investigate (i) associations between adolescents' frequency of breakfast and family functioning (close relations to parents, quality of family communication and family support) and (ii) if any observed associations between breakfast frequency and family functioning vary by sociodemographic factors. DESIGN: School-based cross-sectional study. Students completed a web-based questionnaire. Associations were estimated by multilevel multivariate logistic regression. SETTING: Danish arm of the Health Behaviour in School-aged Children study, 2014. SUBJECTS: Adolescents aged 13 and 15 years (n 3054) from a random sample of forty-one schools. RESULTS: Nearly one-quarter of the adolescents had low breakfast frequency. Low breakfast frequency was associated with low family functioning measured by three dimensions. The OR (95 % CI) of low breakfast frequency was 1.81 (1.40, 2.33) for adolescents who reported no close relations to parents, 2.28 (1.61, 3.22) for adolescents who reported low level of quality of family communication and 2.09 (1.39, 3.15) for adolescents who reported low level of family support. Joint effect analyses suggested that the odds of low breakfast frequency among adolescents with low family functioning compared with high family functioning were highest among adolescents being girls, immigrants and living in other than a traditional family structure. CONCLUSIONS: Low breakfast frequency was associated with low family functioning measured by close relations to parents, quality of family communication and family support. Further, analyses suggested that the associations were more pronounced among girls, immigrants and adolescents from other family structure than traditional. The study highlights the importance of the family setting in promoting regular breakfast frequency among adolescents. PMID- 26865295 TI - Ecological traps: current evidence and future directions. AB - Ecological traps, which occur when animals mistakenly prefer habitats where their fitness is lower than in other available habitats following rapid environmental change, have important conservation and management implications. Empirical research has focused largely on assessing the behavioural effects of traps, by studying a small number of geographically close habitat patches. Traps, however, have also been defined in terms of their population-level effects (i.e. as preferred habitats of sufficiently low quality to cause population declines), and this is the scale most relevant for management. We systematically review the ecological traps literature to (i) describe the geographical and taxonomic distribution of efforts to study traps, (ii) examine how different traps vary in the strength of their effects on preference and fitness, (iii) evaluate the robustness of methods being used to identify traps, and (iv) determine whether the information required to assess the population-level consequences of traps has been considered. We use our results to discuss key knowledge gaps, propose improved methods to study traps, and highlight fruitful avenues for future research. PMID- 26865296 TI - Interspecific shared collective decision-making in two forensically important species. AB - To date, the study of collective behaviour has mainly focused on intraspecific situations: the collective decision-making of mixed-species groups involving interspecific aggregation-segregation has received little attention. Here, we show that, in both conspecific and heterospecific groups, the larvae of two species (Lucilia sericata and Calliphora vomitoria, calliphorid carrion-feeding flies) were able to make a collective choice. In all groups, the choice was made within a few minutes and persisted throughout the period of the experiment. The monitoring of a focal individual within a group showed that these aggregations were governed by attractive and retentive effects of the group. Furthermore, the similarity observed between the conspecific and heterospecific groups suggested the existence of shared aggregation signals. The group size was found to have a stronger influence than the species of necrophagous larvae. These results should be viewed in relation to the well-known correlation between group size and heat generation. This study provides the first experimental examination of the dynamics of collective decision-making in mixed-species groups of invertebrates, contributing to our understanding of the cooperation-competition phenomenon in animal social groups. PMID- 26865297 TI - Transcontinental latitudinal variation in song performance and complexity in house wrens (Troglodytes aedon). AB - There is growing interest in latitudinal effects on animal behaviour and life history. One recent focus is on birdsong, which is hypothesized to be more elaborated or complex in the north temperate zone compared with the tropics. Current evidence is mixed and based on cross-species comparisons, or single species with restricted distributions. We circumvent these limitations using a transcontinental sample of 358 songs from house wrens (Troglodytes aedon) at 281 locations spanning more than 100 degrees of latitude (52 degrees N-55 degrees S) across the Americas. We found a significant latitudinal gradient in several basic elements of song performance and complexity between north temperate and tropical populations. Furthermore, we document convergence in song patterns between populations at higher latitudes in the Northern and Southern Hemispheres. Effects were strongest for the number of elements in a song, and the rate of element production, both increasing towards the poles, with similar but weaker effects for other song dimensions (e.g. number of unique elements, trills and trill rate). We consider possible causes related to variable habitats and morphology, concluding that the shorter breeding seasons at higher latitudes in both hemispheres may favour greater song elaboration to mediate territory competition and mate choice. PMID- 26865298 TI - Prey size diversity hinders biomass trophic transfer and predator size diversity promotes it in planktonic communities. AB - Body size exerts multiple effects on plankton food-web interactions. However, the influence of size structure on trophic transfer remains poorly quantified in the field. Here, we examine how the size diversity of prey (nano-microplankton) and predators (mesozooplankton) influence trophic transfer efficiency (using biomass ratio as a proxy) in natural marine ecosystems. Our results support previous studies on single trophic levels: transfer efficiency decreases with increasing prey size diversity and is enhanced with greater predator size diversity. We further show that communities with low nano-microplankton size diversity and high mesozooplankton size diversity tend to occur in warmer environments with low nutrient concentrations, thus promoting trophic transfer to higher trophic levels in those conditions. Moreover, we reveal an interactive effect of predator and prey size diversities: the positive effect of predator size diversity becomes influential when prey size diversity is high. Mechanistically, the negative effect of prey size diversity on trophic transfer may be explained by unicellular size-based metabolic constraints as well as trade-offs between growth and predation avoidance with size, whereas increasing predator size diversity may enhance diet niche partitioning and thus promote trophic transfer. These findings provide insights into size-based theories of ecosystem functioning, with implications for ecosystem predictive models. PMID- 26865299 TI - Bacterial predator-prey dynamics in microscale patchy landscapes. AB - Soil is a microenvironment with a fragmented (patchy) spatial structure in which many bacterial species interact. Here, we explore the interaction between the predatory bacterium Bdellovibrio bacteriovorus and its prey Escherichia coli in microfabricated landscapes. We ask how fragmentation influences the prey dynamics at the microscale and compare two landscape geometries: a patchy landscape and a continuous landscape. By following the dynamics of prey populations with high spatial and temporal resolution for many generations, we found that the variation in predation rates was twice as large in the patchy landscape and the dynamics was correlated over shorter length scales. We also found that while the prey population in the continuous landscape was almost entirely driven to extinction, a significant part of the prey population in the fragmented landscape persisted over time. We observed significant surface-associated growth, especially in the fragmented landscape and we surmise that this sub-population is more resistant to predation. Our results thus show that microscale fragmentation can significantly influence bacterial interactions. PMID- 26865300 TI - A computational approach to studying ageing at the individual level. AB - The ageing process is actively regulated throughout an organism's life, but studying the rate of ageing in individuals is difficult with conventional methods. Consequently, ageing studies typically make biological inference based on population mortality rates, which often do not accurately reflect the probabilities of death at the individual level. To study the relationship between individual and population mortality rates, we integrated in vivo switch experiments with in silico stochastic simulations to elucidate how carefully designed experiments allow key aspects of individual ageing to be deduced from group mortality measurements. As our case study, we used the recent report demonstrating that pheromones of the opposite sex decrease lifespan in Drosophila melanogaster by reversibly increasing population mortality rates. We showed that the population mortality reversal following pheromone removal was almost surely occurring in individuals, albeit more slowly than suggested by population measures. Furthermore, heterogeneity among individuals due to the inherent stochasticity of behavioural interactions skewed population mortality rates in middle-age away from the individual-level trajectories of which they are comprised. This article exemplifies how computational models function as important predictive tools for designing wet-laboratory experiments to use population mortality rates to understand how genetic and environmental manipulations affect ageing in the individual. PMID- 26865301 TI - What caused extinction of the Pleistocene megafauna of Sahul? AB - During the Pleistocene, Australia and New Guinea supported a rich assemblage of large vertebrates. Why these animals disappeared has been debated for more than a century and remains controversial. Previous synthetic reviews of this problem have typically focused heavily on particular types of evidence, such as the dating of extinction and human arrival, and have frequently ignored uncertainties and biases that can lead to misinterpretation of this evidence. Here, we review diverse evidence bearing on this issue and conclude that, although many knowledge gaps remain, multiple independent lines of evidence point to direct human impact as the most likely cause of extinction. PMID- 26865302 TI - Dimethylsulfoniopropionate, superoxide dismutase and glutathione as stress response indicators in three corals under short-term hyposalinity stress. AB - Corals are among the most active producers of dimethylsulfoniopropionate (DMSP), a key molecule in marine sulfur cycling, yet the specific physiological role of DMSP in corals remains elusive. Here, we examine the oxidative stress response of three coral species (Acropora millepora, Stylophora pistillata and Pocillopora damicornis) and explore the antioxidant role of DMSP and its breakdown products under short-term hyposalinity stress. Symbiont photosynthetic activity declined with hyposalinity exposure in all three reef-building corals. This corresponded with the upregulation of superoxide dismutase and glutathione in the animal host of all three species. For the symbiont component, there were differences in antioxidant regulation, demonstrating differential responses to oxidative stress between the Symbiodinium subclades. Of the three coral species investigated, only A. millepora provided any evidence of the role of DMSP in the oxidative stress response. Our study reveals variability in antioxidant regulation in corals and highlights the influence life-history traits, and the subcladal differences can have on coral physiology. Our data expand on the emerging understanding of the role of DMSP in coral stress regulation and emphasizes the importance of exploring both the host and symbiont responses for defining the threshold of the coral holobiont to hyposalinity stress. PMID- 26865303 TI - Niche-tracking migrants and niche-switching residents: evolution of climatic niches in New World warblers (Parulidae). AB - Differences in life-history traits between tropical and temperate lineages are often attributed to differences in their climatic niche dynamics. For example, the more frequent appearance of migratory behaviour in temperate-breeding species than in species originally breeding in the tropics is believed to have resulted partly from tropical climatic stability and niche conservatism constraining tropical species from shifting their ranges. However, little is known about the patterns and processes underlying climatic niche evolution in migrant and resident animals. We evaluated the evolution of overlap in climatic niches between seasons and its relationship to migratory behaviour in the Parulidae, a family of New World passerine birds. We used ordination methods to measure seasonal niche overlap and niche breadth of 54 resident and 49 migrant species and used phylogenetic comparative methods to assess patterns of climatic niche evolution. We found that despite travelling thousands of kilometres, migrants tracked climatic conditions across the year to a greater extent than tropical residents. Migrant species had wider niches than resident species, although residents as a group occupied a wider climatic space and niches of migrants and residents overlapped extensively. Neither breeding latitude nor migratory distance explained variation among species in climatic niche overlap between seasons. Our findings support the notion that tropical species have narrower niches than temperate-breeders, but does not necessarily constrain their ability to shift or expand their geographical ranges and become migratory. Overall, the tropics may have been historically less likely to experience the suite of components that generate strong selection pressures for the evolution of migratory behaviour. PMID- 26865304 TI - Synergistic interactions of ecosystem services: florivorous pest control boosts crop yield increase through insect pollination. AB - Insect pollination and pest control are pivotal functions sustaining global food production. However, they have mostly been studied in isolation and how they interactively shape crop yield remains largely unexplored. Using controlled field experiments, we found strong synergistic effects of insect pollination and simulated pest control on yield quantity and quality. Their joint effect increased yield by 23%, with synergistic effects contributing 10%, while their single contributions were 7% and 6%, respectively. The potential economic benefit for a farmer from the synergistic effects (12%) was 1.8 times greater than their individual contributions (7% each). We show that the principal underlying mechanism was a pronounced pest-induced reduction in flower lifetime, resulting in a strong reduction in the number of pollinator visits a flower receives during its lifetime. Our findings highlight the importance of non-additive interactions among ecosystem services (ES) when valuating, mapping or predicting them and reveal fundamental implications for ecosystem management and policy aimed at maximizing ES for sustainable agriculture. PMID- 26865305 TI - Pharmacological evidence is consistent with a prominent role of spatial memory in complex navigation. AB - The ability to learn about the spatial environment plays an important role in navigation, migration, dispersal, and foraging. However, our understanding of both the role of cognition in the development of navigation strategies and the mechanisms underlying these strategies is limited. We tested the hypothesis that complex navigation is facilitated by spatial memory in a population of Chrysemys picta that navigate with extreme precision (+/-3.5 m) using specific routes that must be learned prior to age three. We used scopolamine, a muscarinic acetylcholine receptor antagonist, to manipulate the cognitive spatial abilities of free-living turtles during naturally occurring overland movements. Experienced adults treated with scopolamine diverted markedly from their precise navigation routes. Naive juveniles lacking experience (and memory) were not affected by scopolamine, and thereby served as controls for perceptual or non-spatial cognitive processes associated with navigation. Further, neither adult nor juvenile movement was affected by methylscopolamine, a form of scopolamine that does not cross the blood-brain barrier, a control for the peripheral effects of scopolamine. Together, these results are consistent with a role of spatial cognition in complex navigation and highlight a cellular mechanism that might underlie spatial cognition. Overall, our findings expand our understanding of the development of complex cognitive abilities of vertebrates and the neurological mechanisms of navigation. PMID- 26865306 TI - Interactions among ecosystem stressors and their importance in conservation. AB - Interactions between multiple ecosystem stressors are expected to jeopardize biological processes, functions and biodiversity. The scientific community has declared stressor interactions-notably synergies-a key issue for conservation and management. Here, we review ecological literature over the past four decades to evaluate trends in the reporting of ecological interactions (synergies, antagonisms and additive effects) and highlight the implications and importance to conservation. Despite increasing popularity, and ever-finer terminologies, we find that synergies are (still) not the most prevalent type of interaction, and that conservation practitioners need to appreciate and manage for all interaction outcomes, including antagonistic and additive effects. However, it will not be possible to identify the effect of every interaction on every organism's physiology and every ecosystem function because the number of stressors, and their potential interactions, are growing rapidly. Predicting the type of interactions may be possible in the near-future, using meta-analyses, conservation-oriented experiments and adaptive monitoring. Pending a general framework for predicting interactions, conservation management should enact interventions that are robust to uncertainty in interaction type and that continue to bolster biological resilience in a stressful world. PMID- 26865307 TI - Touch sensation by pectoral fins of the catfish Pimelodus pictus. AB - Mechanosensation is fundamental to many tetrapod limb functions, yet it remains largely uninvestigated in the paired fins of fishes, limb homologues. Here we examine whether membranous fins may function as passive structures for touch sensation. We investigate the pectoral fins of the pictus catfish (Pimelodus pictus), a species that lives in close association with the benthic substrate and whose fins are positioned near its ventral margin. Kinematic analysis shows that the pectoral fins are held partially protracted during routine forward swimming and do not appear to generate propulsive force. Immunohistochemistry reveals that the fins are highly innervated, and we observe putative mechanoreceptors at nerve fibre endings. To test for the ability to sense mechanical perturbations, activity of fin ray nerve fibres was recorded in response to touch and bend stimulation. Both pressure and light surface brushing generated afferent nerve activity. Fin ray nerves also respond to bending of the rays. These data demonstrate for the first time that membranous fins can function as passive mechanosensors. We suggest that touch-sensitive fins may be widespread in fishes that maintain a close association with the bottom substrate. PMID- 26865309 TI - Flexible, transparent and exceptionally high power output nanogenerators based on ultrathin ZnO nanoflakes. AB - Novel nanogenerator structures composed of ZnO nanoflakes of less than 10 nm thickness were fabricated using a novel method involving a facile synthetic route and a rational design. The fabricated nanogenerators exhibited a short-circuit current density of 67 MUA cm(-2), a peak-to-peak open-circuit voltage of 110 V, and an overall output power density exceeding 1.2 mW cm(-2), and to the best of our knowledge, these are the best values that have been reported so far in the literature on ZnO-based nanogenerators. We demonstrated that our nanogenerator design could instantaneously power 20 commercial green light-emitting diodes without any additional energy storage processes. Both the facile synthetic route for the ZnO nanoflakes and the straightforward device fabrication process present great scaling potential in order to power mobile and personal electronics that can be used in smart wearable systems, transparent and flexible devices, implantable telemetric energy receivers, electronic emergency equipment, and other self-powered nano/micro devices. PMID- 26865308 TI - The effect of disease on the evolution of females and the genetic basis of sex in populations with cytoplasmic male sterility. AB - The evolution of separate males and females is an important evolutionary transition that has occurred multiple times in flowering plants. While empirical studies have stressed the potential importance of natural enemies and organismal interactions in the evolution of separate sexes, there has been no treatment of natural enemies in the theoretical literature. We investigated the effects of disease on the evolution of females in gynodioecious populations composed of females and hermaphrodites, where sex is determined by the interaction of cytoplasmic male sterility (CMS) and nuclear restorer genes. When females are significantly more resistant than hermaphrodites, disease drives an increase in the frequency of females and sex determination becomes nuclear, creating the pre conditions for the evolution of separate males and females. However, when females are only moderately more resistant, disease drives changes in the frequency of CMS and restorer alleles, but has little effect on the frequency of females. We discuss our results in the context of the evolution of mating systems and cyto nuclear epistasis. PMID- 26865310 TI - Physical and mechanical properties of Tunisian women hair. AB - BACKGROUND: Mechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. The aim of this study was to analyse the physical and mechanical properties of Tunisian women's hair. METHODS: Surface characteristics were determined with scanning electron microscopy (SEM). Mechanical properties were studied using the Miniature Tensile Tester Model 675 (MTT675), and the Fibre Dimensional Analysis Unit Model 765 (FDAS765) of Dia-Stron, UK, was used to measure the cross-sectional area. RESULTS: The cross-sectional area, stress at break, strain at break, elastic modulus and total work were 4643.21 +/- 817 MUm(2) , 201 +/- 11.26 MPa, 47.3 +/- 3.6%, 3.1 +/- 0.16 GPa, and 9 +/- 2.2 mJ, respectively. The effects of the factors 'hair curliness' and 'age' on the physical and mechanical properties were studied. The cross-sectional area and the break load are influenced by the factors 'age' and 'curl type', whereas Young's modulus shows a significant dependency only on the age. CONCLUSION: Tunisian women hair presented good mechanical properties as shown by a greater breaking stress and higher breaking strain. Both curl type and age are important factors to consider when evaluating the behaviour of hair. PMID- 26865311 TI - A simplified approach for molecular classification of glioblastomas (GBMs): experience from a tertiary care center in India. AB - This study aims to establish a simplified molecular classification of glioblastomas (GBMs) based on molecular genetic alterations. GBM cases (n-114) were evaluated for IDH-1 and TP53 mutation by Sanger sequencing, PDGFRA and EGFR amplification by FISH, NF1 and YKL40 expression by qRT-PCR. Subsequently they were classified into four subgroups: classical like (CL), proneural like (PN), mesenchymal like (MES) and neural like (NEU). CL subtype was most frequent (39 %), followed by PN (32 %) and MES (20 %) subtypes. PN subtype had significantly younger age at presentation and longest survival (median PFS-82.5 weeks; 1 and 2 years OS-90.6 and 71.3 %). Other three subgroups had equally poor prognosis and hence, clubbed together as non-proneural (Non-PN) (median PFS-39 weeks; 1 and 2 years OS-66 and 0 %). Hence, we recommended this relatively easy method of subclassifying GBMs into PN and Non-PN which are statistically different in prognosis (both OS and PFS on uni and multivariate analysis). Although evaluation of six molecular alterations for identifying these two subgroups is still cumbersome, we propose segregation of PN subtype alone based on assessment of IDH1, TP53 and PDGFRA status, which is relatively easy and may be amenable to routine practice. PMID- 26865312 TI - Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone Backbone Interaction Motifs. AB - Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions. PMID- 26865314 TI - AMPK and SREBP-1c mediate the anti-adipogenic effect of beta hydroxyisovalerylshikonin. AB - beta-hydroxyisovalerylshikonin (beta-HIVS), which is a natural naphthoquinone compound, is one of the main chemicals isolated from a therapeutic plant, Lithospermum erythrorhizon. In the present study, we demonstrated that beta-HIVS inhibited the adipogenesis of 3T3-L1 cells through AMP-activated protein kinase (AMPK)-mediated modulation of sterol regulatory element binding protein (SREBP) 1c. The anti-adipogenic effect of beta-HIVS was accompanied by the increased phosphorylation of AMPK and precursor SREBP-1c. In beta-HIVS-treated 3T3-L1 cells, AMPK was activated and phosphorylated precursor SREBP-1c, preventing the cleavage of precursor SREBP-1c to mature SREBP-1c. Expression of the fat-forming enzymes, acetyl-CoA carboxylase (ACC)1, fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD)1, which are transcribed by mature SREBP-1c, were downregulated, resulting in reduced intracellular fat accumulation. The anti adipogenic effect of beta-HIVS was significantly attenuated by AMPK knockdown. Knockdown of AMPK using siRNA decreased the phosphorylation of precursor SREBP-1c and increased the levels of mature SREBP. The levels of the fat-forming enzymes, ACC1, FAS and SCD1, as well as intracellular fat accumulation were also significantly increased by AMPK knockdown. These results suggest that beta-HIVS activated AMPK, which was followed by the downregulation of mature SREBP-1c and fat-forming enzymes, leading to the inhibition of adipogenesis. PMID- 26865315 TI - Redox mediated synthesis of hierarchical Bi2O3/MnO2 nanoflowers: a non-enzymatic hydrogen peroxide electrochemical sensor. AB - Uniform hierarchical Bi2O3/MnO2 nanoflowers (BM NFs) are fabricated via a reaction strategy by combining redox reaction and hydrothermal treatment. This wet chemical method reports for the first time a one pot synthesis of Bi2O3/MnO2 nanoflowers via a thermodynamically allowed galvanic reaction between Bi(0) and KMnO4 in aqueous solution under modified hydrothermal (MHT) conditions. The Bi2O3/MnO2 NF composites are then applied as a catalyst for electrochemical hydrogen peroxide detection. Exceedingly high H2O2 detection sensitivity (0.914 MUA MUM(-1) cm(-2)) lies in a wide linear range of 0.2-290 MUM and the detection limit goes down to 0.05 MUM (S/N = 3) for non-enzymatic detection of H2O2 in solution. This prototype sensor demonstrates an admirable analytical performance considering its long-term stability, good reproducibility and acceptable selectivity against common interfering species. The employment of the stable nanocomposite for real sample analysis makes it a deliverable for H2O2 sensing. PMID- 26865313 TI - The Differential Levels of Inflammatory Cytokines and BDNF among Bipolar Spectrum Disorders. AB - OBJECTIVE: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective. METHODS: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-alpha, C reactive protein, transforming growth factor-beta1, and interleukin-8) and brain derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups. RESULTS: Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-alpha, transforming growth factor-beta1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar I disorder patients had significantly higher IL-8 levels than did bipolar II disorder and other specified bipolar disorder with short duration hypomania patients in multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar II disorder and other specified bipolar disorder with short duration hypomania patients were nonsignificant. CONCLUSION: The immunological disturbance along the bipolar spectrum was most severe in bipolar I disorder patients. Other specified bipolar disorder with short duration hypomania patients and bipolar II disorder patients did not differ in these biological markers. PMID- 26865316 TI - Learning (from) the errors of a systems biology model. AB - Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge. PMID- 26865317 TI - Bioinspired Interfacial Materials with Enhanced Drop Mobility: From Fundamentals to Multifunctional Applications. AB - The development of bioinspired interfacial materials with enhanced drop mobility that mimic the innate functionalities of nature will have a significant impact on the energy, environment and global healthcare. Despite extensive progress, state of the art interfacial materials have not reached the level of maturity sufficient for industrial applications in terms of scalability, stability, and reliability. These are complicated by their operating environments and lack of facile approaches to control the local structural texture and chemical composition at multiple length scales. The recent advances in the fundamental understanding are reviewed, as well as practical applications of bioinspired interfacial materials, with an emphasis on the drop bouncing and coalescence induced jumping behaviors. Perspectives on how to catalyze new discoveries and to foster technological adoption to move this exciting area forward are also suggested. PMID- 26865318 TI - Associations between informal care, disease, and risk factors: A Spanish country wide population-based study. AB - This population-based study using 2011-2012 Spanish National Health Survey data aimed to measure the impact of disease, health-related habits, and risk factors associated with informal caregiving. We included and matched self-reported informal caregivers [ICs] with controls (1:4) from the same survey. For each outcome, we analyzed associations between ICs and controls using linear regression or logistic regression models. ICs had 3.4 per cent more depression (OR: 1.33, 95 per cent confidence intervals [CI]:1.06, 1.68). ICs had lower social support (95 per cent CI: 1.64, 3.28), they did more housework alone (OR:3.6, 95 per cent CI:2.65, 4.89), and had greater stress (95 per cent CI:0.13, 0.83). Women ICs caring alone had more anxiety than other groups. We found no statistical association between caregivers and worse health-related habits or increased risk factors (less physical activity, smoking, drinking, and cholesterol). Our results provide evidence that health-care professionals and organizations should recognize the importance of caring for those who care. PMID- 26865319 TI - An overview about the medical use of antifungals in Portugal in the last years. AB - Despite the introduction of new antifungal agents, the frequency of invasive and mucocutaneous fungal infections as well as resistance to antifungal drugs continues to increase. Over 300 million persons are infected annually with fungi. Resistance to antimicrobials is one of today's major health threats. Can the possible causes of fungal antimicrobial resistance be understood and prevented to minimize risks to public health. We provide an overview of antifungal drug use in European countries, particularly Portugal. We reviewed prescriptions for and over the-counter sales (OTC) of azoles in Portuguese pharmacies and in alternative shops. We conclude that in Portugal, azole antifungal sales, as well as medical prescribed azoles are very high. The Portuguese population consumes more antifungal drugs per capita than others in Europe. PMID- 26865320 TI - Misconceptions about Ebola virus disease among lay people in Guinea: Lessons for community education. AB - To characterize the perception of Ebola virus disease (EVD) in Guinea, we administered, from November 2014 to February 2015, a questionnaire to a convenience sample of 200 lay people in Conakry and a group of 8 physicians. We found widespread misconceptions among lay people, including that praying to God can protect against EVD, that traditional healers are more competent than physicians in treating EVD, that people get infected through physical proximity without contact, that the Ebola epidemic is the result of Western bioterrorism experiments, that Western medical staff disseminated the virus, and that the purpose of quarantine measures is to hasten the death of Ebola patients. Major educational interventions, sensitive to local cultural beliefs, are needed to overcome the misconceptions about Ebola in Guinea. PMID- 26865321 TI - High-Dose Sedation and Analgesia During Extracorporeal Membrane Oxygenation: A Focus on the Adjunctive Use of Ketamine. AB - Use of ketamine in patients requiring extracorporeal membrane oxygenation (ECMO) has rarely been reported, and the optimal dosing strategy remains unclear. A patient admitted with hypoxic respiratory failure required ECMO in addition to continuous infusion of low-dose ketamine following titration of opioid and sedative medications to high doses. After initiation of ketamine, infusion rates of opioids and/or sedatives were maintained or decreased. Recorded Richmond Agitation-Sedation Scale (RASS) scores were -4 to -5 and documented pain scores were 0. No adverse effects were reported while receiving low-dose ketamine. This case illustrates that use of low-dose ketamine infusion may be a useful adjunctive agent in patients receiving ECMO and high-dose opioid and sedative medications. PMID- 26865322 TI - Image-Reversal Soft Lithography: Fabrication of Ultrasensitive Biomolecular Detectors. AB - Image-reversal soft lithography enables the straightforward fabrication of high performance biosensors without requiringhigh-resolution photolitography. PMID- 26865324 TI - Using Evidence-Based Design to Improve Pharmacy Department Efficiency. AB - Using a case study of a pharmacy department rebuild in the South West of England, this article examines the use of evidence-based design to improve the efficiency and staff well-being with a new design. This article compares three designs, the current design, an anecdotal design, and an evidence-based design, to identify how evidence-based design can improve efficiency and staff well-being by reducing walking time and distance. Data were collected from the existing building and used to measure the efficiency of the department in its current state. These data were then mapped onto an anecdotal design, produced by architects from interviews and workshops with the end users, and an evidence-based design, produced by highlighting functions with high adjacencies. This changed the view on the working processes within the department, shifting away from a focus on the existing robotic dispensing system. Using evidence-based design was found to decrease the walking time and distance for staff by 24%, as opposed to the anecdotal design, which increased these parameters by 9%, and is predicted to save the department 248 min across 2 days in staff time spent walking. PMID- 26865323 TI - Transcriptomic, proteomic and metabolic changes in Arabidopsis thaliana leaves after the onset of illumination. AB - BACKGROUND: Light plays an important role in plant growth and development. In this study, the impact of light on physiology of 20-d-old Arabidopsis leaves was examined through transcriptomic, proteomic and metabolomic analysis. Since the energy-generating electron transport chains in chloroplasts and mitochondria are encoded by both nuclear and organellar genomes, sequencing total RNA after removal of ribosomal RNAs provides essential information on transcription of organellar genomes. The changes in the levels of ADP, ATP, NADP(+), NADPH and 41 metabolites upon illumination were also quantified. RESULTS: Upon illumination, while the transcription of the genes encoded by the plastid genome did not change significantly, the transcription of nuclear genes encoding different functional complexes in the photosystem are differentially regulated whereas members of the same complex are co-regulated with each other. The abundance of mRNAs and proteins encoded by all three genomes are, however, not always positively correlated. One such example is the negative correlation between mRNA and protein abundances of the photosystem components, which reflects the importance of post transcriptional regulation in plant physiology. CONCLUSION: This study provides systems-wide datasets which allow plant researchers to examine the changes in leaf transcriptomes, proteomes and key metabolites upon illumination and to determine whether there are any correlations between changes in transcript and protein abundances of a particular gene or pathway upon illumination. The integration of data of the organelles and the photosystems, Calvin-Benson cycle, carbohydrate metabolism, glycolysis, the tricarboxylic acid cycle and respiratory chain, thereby provides a more complete picture to the changes in plant physiology upon illumination than has been attained to date. PMID- 26865325 TI - Effect of Instrument Lubricants on the Surface Degree of Conversion and Crosslinking Density of Nanocomposites. AB - PURPOSE: The surface degree of conversion and crosslink density of composites should not be affected by the use of instrument lubricants in order to provide long-lasting tooth restorations. This study aimed to analyze the effect of instrument lubricants on the degree of conversion and crosslink density of nanocomposites. MATERIALS AND METHODS: Samples (N = 10) were fabricated according to the composites (Filtek Z350 XT, 3M ESPE, St. Paul, MN, USA; and IPS Empress Direct, Ivoclar Vivadent AG, Schaan, Liechtenstein and lubricants used (Adper Single Bond 2 and Scotchbond Multi-Purpose bonding agent adhesive systems, 3M ESPE; 70% ethanol, absolute ethanol, and no lubricant). Single composite increments were inserted into a Teflon mold using the same dental instrument. The composite surface was then modeled using a brush wiped with each adhesive system and a spatula wiped with each ethanol. The control group was fabricated with no additional modeling. The surface degree of conversion and crosslink density were measured by Fourier transform infrared spectroscopy and the hardness decrease test, respectively. Data were analyzed using two-way analysis of variance and the Tukey's test (p < 0.05). RESULTS: Filtek Z350 XT showed statistically similar degree of conversion regardless of the lubricant used, whereas the use of adhesive systems and 70% ethanol decreased the degree of conversion for IPS Empress Direct. Only Scotchbond Multi-Purpose bonding agent decreased crosslink density for Filtek Z350 XT, whereas both adhesive systems decreased crosslink density for IPS Empress Direct. CONCLUSION: Filtek Z350 XT appeared to be less sensitive to the effects of lubricants, and absolute ethanol did not affect the degree of conversion and crosslink density of the nanocomposites tested. CLINICAL SIGNIFICANCE: Although the use of lubricants may be recommended to minimize the stickiness of dental instruments and composite resin, dentists should choose materials that do not have a negative effect on the surface properties of composites. Only the use of absolute ethanol safely maintains the surface integrity of nanocomposites in comparison with adhesive system and 70% ethanol. PMID- 26865326 TI - Phylogenetic Characterization Genome Segment 2 of Bluetongue Virus Strains Belonging to Serotypes 5, 7 and 24 Isolated for the First Time in China During 2012 to 2014. AB - Bluetongue is endemic in China, and Bluetongue virus (BTV) strains belonging to eight different serotypes (BTV-1, BTV-2, BTV-3, BTV-4, BTV-9, BTV-12, BTV-15 and BTV-16) had been isolated between 1996 and 1997. However, there has been a long pause in investigating the epidemiology of BTV infection since then. During 2012 2014, eight BTV strains belonging to serotypes 5, 7 and 24 were isolated for the first time in Yunnan and Guangdong provinces from the blood of sentinel animals. Phylogenetic analyses of genome segment 2 of these Chinese BTV strains grouped them into nucleotypes E, F and A, respectively, along with the reference strains of the same serotype. For each serotype, Chinese strains cluster together closely to form a China's sublineage. In addition, these strains were most closely related to strains from Africa, indicating that they may share a recent common ancestry with African strains. To our knowledge, this is the first time that BTV 5, BTV-7 and BTV-24 strains have been isolated in South-East Asia. These data will be beneficial for understanding the BTV epidemiology and improving diagnostic assays and control measures against bluetongue in China and its neighbouring countries in the Asia-Pacific region. PMID- 26865328 TI - Characterization of arsenite tolerant Halomonas sp. Alang-4, originated from heavy metal polluted shore of Gulf of Cambay. AB - Arsenite [As(III)]-oxidizing bacteria were isolated from heavy metal contaminated shore of Gulf of Cambay at Alang, India. The most efficient bacterial strain Alang-4 could tolerate up to 15 mM arsenite [As(III)] and 200 mM of arsenate [As(V)]. Its 16S rRNA gene sequence was 99% identical to the 16S rRNA genes of genus Halomonas (Accession no. HQ659187). Arsenite oxidase enzyme localized on membrane helped in conversion of As(III) to As(V). Arsenite transporter genes (arsB, acr3(1) and acr3(2)) assisted in extrusion of arsenite from Halomonas sp. Alang-4. Generation of ROS in response to arsenite stress was alleviated by higher activities of catalase, ascorbate peroxidase, superoxide dismutase and glutathione S-transferase enzymes. Down-regulation in the specific activities of nearly all dehydrogenases of carbon assimilatory pathway viz., glucose-6 phosphate, pyruvate, alpha-ketoglutarate, isocitrate and malate dehydrogenases, was observed in presence of As(III), whereas, the specific activities of phosphoenol pyruvate carboxylase, pyruvate carboxylase and isocitrate lyase enzymes were found to increase two times in As(III) treated cells. The results suggest that in addition to efficient ars operon, alternative pathways of carbon utilization exist in the marine bacterium Halomonas sp. Alang-4 to overcome the toxic effects of arsenite on its dehydrogenase enzymes. PMID- 26865327 TI - Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population. AB - The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships. PMID- 26865331 TI - The use of a gas chromatography-sensor system combined with advanced statistical methods, towards the diagnosis of urological malignancies. AB - Prostate cancer is one of the most common cancers. Serum prostate-specific antigen (PSA) is used to aid the selection of men undergoing biopsies. Its use remains controversial. We propose a GC-sensor algorithm system for classifying urine samples from patients with urological symptoms. This pilot study includes 155 men presenting to urology clinics, 58 were diagnosed with prostate cancer, 24 with bladder cancer and 73 with haematuria and or poor stream, without cancer. Principal component analysis (PCA) was applied to assess the discrimination achieved, while linear discriminant analysis (LDA) and support vector machine (SVM) were used as statistical models for sample classification. Leave-one-out cross-validation (LOOCV), repeated 10-fold cross-validation (10FoldCV), repeated double cross-validation (DoubleCV) and Monte Carlo permutations were applied to assess performance. Significant separation was found between prostate cancer and control samples, bladder cancer and controls and between bladder and prostate cancer samples. For prostate cancer diagnosis, the GC/SVM system classified samples with 95% sensitivity and 96% specificity after LOOCV. For bladder cancer diagnosis, the SVM reported 96% sensitivity and 100% specificity after LOOCV, while the DoubleCV reported 87% sensitivity and 99% specificity, with SVM showing 78% and 98% sensitivity between prostate and bladder cancer samples. Evaluation of the results of the Monte Carlo permutation of class labels obtained chance like accuracy values around 50% suggesting the observed results for bladder cancer and prostate cancer detection are not due to over fitting. The results of the pilot study presented here indicate that the GC system is able to successfully identify patterns that allow classification of urine samples from patients with urological cancers. An accurate diagnosis based on urine samples would reduce the number of negative prostate biopsies performed, and the frequency of surveillance cystoscopy for bladder cancer patients. Larger cohort studies are planned to investigate the potential of this system. Future work may lead to non-invasive breath analyses for diagnosing urological conditions. PMID- 26865329 TI - Functional role of positively selected amino acid substitutions in mammalian rhodopsin evolution. AB - Visual rhodopsins are membrane proteins that function as light photoreceptors in the vertebrate retina. Specific amino acids have been positively selected in visual pigments during mammal evolution, which, as products of adaptive selection, would be at the base of important functional innovations. We have analyzed the top candidates for positive selection at the specific amino acids and the corresponding reverse changes (F13M, Q225R and A346S) in order to unravel the structural and functional consequences of these important sites in rhodopsin evolution. We have constructed, expressed and immunopurified the corresponding mutated pigments and analyzed their molecular phenotypes. We find that position 13 is very important for the folding of the receptor and also for proper protein glycosylation. Position 225 appears to be important for the function of the protein affecting the G-protein activation process, and position 346 would also regulate functionality of the receptor by enhancing G-protein activation and presumably affecting protein phosphorylation by rhodopsin kinase. Our results represent a link between the evolutionary analysis, which pinpoints the specific amino acid positions in the adaptive process, and the structural and functional analysis, closer to the phenotype, making biochemical sense of specific selected genetic sequences in rhodopsin evolution. PMID- 26865333 TI - Visible light-induced intramolecular dearomative cyclization of alpha-bromo-N benzyl-alkylamides: efficient construction of 2-azaspiro[4.5]decanes. AB - An efficient intramolecular dearomative cyclization via visible light-induced photoredox catalysis allows for a highly regioselective dearomative cyclization of alpha-bromo-N-benzyl-alkylamides to construct 2-azaspiro[4.5]decanes in the presence of an iridium catalyst. PMID- 26865332 TI - A comparison of 4-Fr with 5-Fr endoscopic nasopancreatic drainage catheters: A randomized, controlled trial. AB - BACKGROUND AND AIM: Although endoscopic nasopancreatic drainage (ENPD) is useful for collecting samples for pancreatic juice cytology and for treating leakage of pancreatic juice and occlusive pancreatitis, placement of the ENPD catheter is associated with complications such as post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We investigated whether an ENPD catheter with a smaller diameter could reduce the incidence of complications. METHODS: Patients requiring placement of an ENPD catheter (n = 254) were enrolled and randomly assigned to one of two catheter-size groups: the 4-Fr group or the 5 Fr group. The incidence of PEP, cholangitis, and spontaneous catheter displacement and the suitability of pancreatic juice cytology samples were compared between groups. In addition, univariate and multivariate analyses were conducted on factors associated with PEP. RESULTS: The incidence of PEP was significantly lower in the 4-Fr group compared with the 5-Fr group (4.1% vs 12.4%, respectively; P = 0.021). The rate of cholangitis and spontaneous catheter displacement and the suitability of pancreatic juice cytology samples did not differ between groups. Multivariate analysis revealed that the risk of PEP was 3.7 times higher when using a 5-Fr catheter than when using a 4-Fr catheter (P = 0.019). In addition, the risk of PEP was 4.1 times higher in patients with an intraductal papillary mucinous neoplasm than in those without (P = 0.0049) and 4.6 times higher in patients aged <65 than in those aged >=65 (P = 0.0033). CONCLUSIONS: A 4-Fr catheter is as useful as a 5-Fr catheter and is associated with a significantly lower incidence of PEP. PMID- 26865335 TI - Microscopic versus endoscopic transsphenoidal surgery for pituitary adenoma: analysis of surgical safety in 221 consecutive patients. PMID- 26865336 TI - Antimicrobial activity of lactobacillus strains against uropathogens. AB - BACKGROUND: The use of lactobacillus probiotics has been proposed as an alternative to prophylactic antibiotics for preventing urinary tract infection (UTI) in the era of antibiotic resistance. In this study, the antimicrobial activity of lactobacillus strains against uropathogens, was evaluated and compared with that of antibiotics. METHODS: To evaluate inhibitory activities of lactobacilli against uropathogens, six lactobacillus strains (L. gasseri, L. rhamnosus, L. acidophilus, L. plantarum, L. paracasei, L. acidophilus) and four representative uropathogens of infantile UTI (extended-spectrum beta-lactamase [ESBL](-) Escherichia coli, ESBL(+) E. coli, Proteus vulgaris, Enterococcus fecalis) were selected. Lactobacillus strain in vitro inhibition of each uropathogen was evaluated on MRS agar well diffusion assay and compared with that of commercial antibiotic discs. RESULTS: Average inhibitory zone for each of the six lactobacillus strains against the four uropathogens showed slightly different but consistent inhibition (inhibitory zone diameter, 10.5-20.0 mm). This was different to that of the antibiotic discs, which had a wider range of inhibition (inhibitory zone diameter, <6.0-27.5 mm) depending on the uropathogen resistance pattern. The inhibitory zone of the six lactobacillus strains was between that of sensitive and resistant antibiotics (P < 0.05). CONCLUSIONS: Lactobacillus strains had similar moderate antimicrobial activities against uropathogens. Further research is needed to ascertain the strains with the best probiotic potential. PMID- 26865334 TI - Iron stimulates plasma-activated medium-induced A549 cell injury. AB - Non-thermal atmospheric pressure plasma is applicable to living cells and has emerged as a novel technology for cancer therapy. Plasma has recently been shown to affect cells not only by direct irradiation, but also by indirect treatments with previously prepared plasma-activated medium (PAM). Iron is an indispensable element but is also potentially toxic because it generates the hydroxyl radical (*OH) in the presence of hydrogen peroxide (H2O2) via the Fenton reaction. The aim of the present study was to demonstrate the contribution of iron to PAM induced A549 adenocarcinoma cell apoptosis. We detected the generation of *OH and elevation of intracellular ferrous ions in PAM-treated cells and found that they were inhibited by iron chelator. The elevations observed in ferrous ions may have been due to their release from the intracellular iron store, ferritin. Hydroxyl radical-induced DNA injury was followed by the activation of poly(ADP-ribose) polymerase-1, depletion of NAD(+) and ATP, and elevations in intracellular Ca(2+). The sensitivities of normal cells such as smooth muscle cells and keratinocytes to PAM were less than that of A549 cells. These results demonstrated that H2O2 in PAM and/or *OH generated in the presence of iron ions disturbed the mitochondrial-nuclear network in cancer cells. PMID- 26865337 TI - Pediatric oncologists' coping strategies for dealing with patient death. AB - This research examined pediatric oncologists coping strategies when their patients died of cancer. Twenty-one pediatric oncologists at 2 Canadian pediatric academic hospitals were interviewed about their coping strategies when patients died or were in the process of dying. The grounded theory method of data collection and data analysis were used. Line-by-line coding was used to establish codes and themes and constant comparison was used to establish relations among emerging codes and themes. Pediatric oncologists used engagement coping strategies with primary and secondary responses including emotional regulation (social support and religion), problem solving (supporting families at end of life), cognitive restructuring (making a difference and research), and distraction (breaks, physical activity, hobbies and entertainment, spending time with own children). They also used disengagement coping strategies that included voluntary avoidance (compartmentalization and withdrawing from families at end of life). Given the chronic nature of patient death in pediatric oncology and the emotionally difficult nature of this work, medical institutions such as hospitals have a responsibility to assist pediatric oncologists in coping with this challenging aspect of their work. Future research is needed to evaluate how best to implement these changes on the institutional level to help oncologists cope with patient death and the effect of using these strategies on their quality of life. PMID- 26865338 TI - The effects of anterior palatoplasty on floppy eyelid syndrome patients with obstructive sleep apnea. AB - OBJECTIVES/HYPOTHESIS: To investigate the effects of anterior palatoplasty on the presence and stage of floppy eyelid syndrome (FES) among patients diagnosed with mild or moderate obstructive sleep apnea (OSA) according to the apnea-hypopnea index (AHI). STUDY DESIGN: Prospective controlled trial. METHODS: Those patients whose AHI scores were between 5 and 30 according to full-night polysomnography were included in the study. The patients in whom anterior palatoplasty was performed were included in the study group, whereas those refusing surgery comprised the control group. All patients were evaluated for the presence of FES. The sleep studies were repeated after the third postoperative month, and the results were statistically compared. RESULTS: Sixty-two patients were included in the study. Thirty-five patients who were treated with anterior palatoplasty comprised the study group, and 27 patients were included in the control group. In the surgically treated group, 60% (n = 21) had FES, whereas 55.5% (n = 15) of the control group had FES (P = .798). In the surgically treated group, the FES ratio decreased to 25.7% (n = 9) after the third postoperative month (P = .007). In surgically successful cases, the preoperative-postoperative oxygen desaturation index and preoperative-postoperative lowest oxygen saturation values were 11.755% +/- 9.037% and 6.77% +/- 5.362% (P = .04), and 86.1% +/- 3.89% and 87.8% +/- 2.85%, respectively (P = .124). These values were 12.166% +/- 5.767% and 14.780% +/- 9.924% (P = .385), and 86.13% +/- 4.18% and 85.26% +/- 4.26%, respectively (P = .579), in patients who underwent unsuccessful surgery. CONCLUSIONS: FES presence and stages were decreased following successful anterior palatoplasty surgery. This effect may have resulted from the correction of tissue hypoxia, which is common in the pathophysiology of both OSA and FES. LEVEL OF EVIDENCE: 2b Laryngoscope, 126:2171-2175, 2016. PMID- 26865339 TI - The Plant Polyester Cutin: Biosynthesis, Structure, and Biological Roles. AB - Cutin, a polyester composed mostly of oxygenated fatty acids, serves as the framework of the plant cuticle. The same types of cutin monomers occur across most plant lineages, although some evolutionary trends are evident. Additionally, cutins from some species have monomer profiles that are characteristic of the related polymer suberin. Compositional differences likely have profound structural consequences, but little is known about cutin's molecular organization and architectural heterogeneity. Its biological importance is suggested by the wide variety of associated mutants and gene-silencing lines that show a disruption of cuticular integrity, giving rise to numerous physiological and developmental abnormalities. Mapping and characterization of these mutants, along with suppression of gene paralogs through RNA interference, have revealed much of the biosynthetic pathway and several regulatory factors; however, the mechanisms of cutin polymerization and its interactions with other cuticle and cell wall components are only now beginning to be resolved. PMID- 26865340 TI - The Costs of Photorespiration to Food Production Now and in the Future. AB - Photorespiration is essential for C3 plants but operates at the massive expense of fixed carbon dioxide and energy. Photorespiration is initiated when the initial enzyme of photosynthesis, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), reacts with oxygen instead of carbon dioxide and produces a toxic compound that is then recycled by photorespiration. Photorespiration can be modeled at the canopy and regional scales to determine its cost under current and future atmospheres. A regional-scale model reveals that photorespiration currently decreases US soybean and wheat yields by 36% and 20%, respectively, and a 5% decrease in the losses due to photorespiration would be worth approximately $500 million annually in the United States. Furthermore, photorespiration will continue to impact yield under future climates despite increases in carbon dioxide, with models suggesting a 12-55% improvement in gross photosynthesis in the absence of photorespiration, even under climate change scenarios predicting the largest increases in atmospheric carbon dioxide concentration. Although photorespiration is tied to other important metabolic functions, the benefit of improving its efficiency appears to outweigh any potential secondary disadvantages. PMID- 26865342 TI - Long-term exposure to triphenylphosphate alters hormone balance and HPG, HPI, and HPT gene expression in zebrafish (Danio rerio). AB - With the global decline in the use of polybrominated diphenyl ethers, the demand for alternative flame retardants, such as triphenylphosphate (TPP), has increased substantially. Triphenylphosphate is now detected in various environments including aquatic ecosystems worldwide. However, studies on the toxicological consequences of chronic TPP exposure on aquatic organisms are scarce. The zebrafish model was used to investigate the effects of long-term TPP exposure on the endocrine system. Zebrafish embryos were exposed to 5 ug/L, 50 ug/L, or 500 ug/L TPP for 120 d, and hormonal and transcriptional responses were measured along the hypothalamic-pituitary-gonad (HPG) axis, the hypothalamic-pituitary interrenal (HPI) axis, and the hypothalamic-pituitary-thyroid (HPT) axis. Exposure to TPP significantly increased plasma 17beta-estradiol, but decreased 11 ketotestosterone in both sexes. Gene expression data support these changes. In the HPI axis, plasma cortisol and proopiomelanocortin (pomc) and mineralocorticoid receptor transcripts increased in females, but in males cortisol decreased whereas pomc increased (p < 0.05). Thyroxine and triiodothyronine increased, and thyrotrophin-releasing hormone receptor 2 (trhr2) and trh expression were affected only in females (p < 0.05). In summary, long term exposure to TPP enhanced estrogenicity in both males and females, potentially through influencing the HPG axis, but modulated the HPI, and HPT axes differently by sex, suggesting that both genomic and nongenomic responses might be involved. Environ Toxicol Chem 2016;35:2288-2296. (c) 2016 SETAC. PMID- 26865347 TI - Assessing the protection of the nanomaterial workforce. AB - Responsible development of any technology, including nanotechnology, requires protecting workers, the first people to be exposed to the products of the technology. In the case of nanotechnology, this is difficult to achieve because in spite of early evidence raising health and safety concerns, there are uncertainties about hazards and risks. The global response to these concerns has been the issuance by authoritative agencies of precautionary guidance to strictly control exposures to engineered nanomaterials (ENMs). This commentary summarizes discussions at the "Symposium on the Health Protection of Nanomaterial Workers" held in Rome (25 and 26 February 2015). There scientists and practitioners from 11 countries took stock of what is known about hazards and risks resulting from exposure to ENMs, confirmed that uncertainties still exist, and deliberated on what it would take to conduct a global assessment of how well workers are being protected from potentially harmful exposures. PMID- 26865348 TI - Nutritional consequences of folivory in a small-bodied lemur (Lepilemur leucopus): Effects of season and reproduction on nutrient balancing. AB - OBJECTIVES: Small-bodied folivores are rare because processing leaves often requires extensive gut adaptations and lengthy retention times for fiber fermentation. However, the <1 kg nocturnal white-footed sportive lemurs (Lepilemur leucopus) persist on a leaf-based diet. We investigated how extrinsic (i.e., seasonality in temperature and food availability) and intrinsic factors (i.e., reproductive state) influence nutrient intake and explored how nutrient and energy needs are met in this species. MATERIALS AND METHODS: We conducted full night focal follows across all seasons and analyzed nutrients in all items eaten by adults of both sexes to investigate nutrient intake and nutritional priorities in L. leucopus. We estimated digestible protein content, as this is a biologically more meaningful measure than crude protein. RESULTS: Protein intake was constant across seasons, while non-protein energy and dry matter intake increased from the hot wet to the cold dry season. Males and females did not differ in their nutrient or apparent energy intake irrespective of female reproductive state. DISCUSSION: We conclude that these animals prioritize protein over non-protein energy intake as dietary protein is in limited supply, and that thermoregulation poses higher energetic costs than reproduction in this species. While protein intake did not differ across female reproductive states, the relative protein content of the diet was highest during the lactation period, indicating that the balance of non-protein to protein intake may be more important than absolute intake. Dry matter intake was high compared to other folivorous primates, indicating that L. leucopus follows an intake rather than an efficiency strategy to meet its energy requirements. Am J Phys Anthropol 160:197 207, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26865341 TI - The Conservation and Function of RNA Secondary Structure in Plants. AB - RNA transcripts fold into secondary structures via intricate patterns of base pairing. These secondary structures impart catalytic, ligand binding, and scaffolding functions to a wide array of RNAs, forming a critical node of biological regulation. Among their many functions, RNA structural elements modulate epigenetic marks, alter mRNA stability and translation, regulate alternative splicing, transduce signals, and scaffold large macromolecular complexes. Thus, the study of RNA secondary structure is critical to understanding the function and regulation of RNA transcripts. Here, we review the origins, form, and function of RNA secondary structure, focusing on plants. We then provide an overview of methods for probing secondary structure, from physical methods such as X-ray crystallography and nuclear magnetic resonance (NMR) imaging to chemical and nuclease probing methods. Combining these latter methods with high-throughput sequencing has enabled them to scale across whole transcriptomes, yielding tremendous new insights into the form and function of RNA secondary structure. PMID- 26865349 TI - A retrospective comparison of infliximab versus adalimumab as induction and maintenance therapy for Crohn disease. AB - BACKGROUND: In Australia, infliximab (IFX) and adalimumab (ADA) are available for the treatment of moderate-severe Crohn disease (CD) refractory to conventional therapies, with minimal local data comparing their efficacy. AIM: The aim of this study was to compare clinical and biochemical outcomes at 3 and 12 months between patients receiving induction and maintenance therapy with IFX versus ADA. METHODS: Retrospective single-centre audit of all patients commenced on IFX or ADA as their first anti-tumour necrosis factor agent between July 2007 and May 2012. Clinical and biochemical parameters were compared pre-commencement, 3 and 12 months post-commencement. RESULTS: A total of 81 patients was included in the study; 63 IFX-treated and 18 ADA-treated. Significant Crohn disease activity index (CDAI) reductions were noted within both groups at 3 months (P < 0.001) and 12 months (P < 0.001). Similarly, significant reductions were noted in steroid doses within groups at 3 months (P < 0.05) and 12 months (P < 0.05), with notable reductions in C-reactive protein (CRP) at 3 months within groups (P < 0.05). Adverse events occurred in 14.3% of IFX and 11.1% of ADA patients. Comparing IFX with ADA, no difference was shown between groups in CDAI reductions at 3 months (P = 0.94) and 12 months (P = 0.95), steroid dosing at 3 months (P = 0.23) and 12 months (P = 0.81), and CRP reduction at 3 months (P = 0.33) and 12 months (P = 0.62). Fistula-related admissions were significantly reduced in IFX patients (100% reduction post-IFX vs 66.7% post-ADA) (P = 0.01). CONCLUSION: Clinical and biochemical outcomes were similar in patients treated with IFX or ADA as induction and maintenance therapy for CD. However, significant reductions were noted in admissions relating to fistulising disease in IFX patients. PMID- 26865350 TI - Randomized, Multicenter, Double-Blind Study of the Safety and Efficacy of 1%D-3 Hydroxybutyrate eye drops for Dry Eye Disease. AB - In a previous study, we demonstrated that topical D-beta-hydroxybutyrate ameliorates corneal epithelial erosion and superficial punctate keratopathy in a rat model of dry eye disease. In the current investigation, we performed a prospective, randomized, multicentre, double-blind, placebo-controlled study to assess the safety and efficacy of 1% D-3-hydroxybutyrate eye drops in patients with dry eye disease. A total of 65 patients were randomly assigned to either the placebo group or the 1% D-3-hydroxybutyrate group, and the treatments were administered 6 times a day for 4 weeks. We then evaluated corneal fluorescein staining, corneal and conjunctival rose Bengal staining, tear film break-up time (BUT), Schirmer score, and subjective symptoms. At both 2 and 4 weeks, the corneal rose Bengal score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group. Among patients with an initial Schirmer score of <=5 mm, the corneal fluorescein staining score was significantly better in the 1% D-3-hydroxybutyrate group than in the placebo group at two weeks. Mild ocular symptoms occurred in both groups, and these spontaneously resolved. The present study suggested that 1% D-3-hydroxybutyrate eye drops are safe and effective in treating ocular surface disorders in patients with tear-deficient dry eye disease. PMID- 26865352 TI - A safety evaluation of imatinib mesylate in the treatment of gastrointestinal stromal tumor. AB - INTRODUCTION: For the last 15 years, imatinib mesylate has been the first line treatment of choice for advanced (metastatic) GIST. AREAS COVERED: This review describes key efficacy data on imatinib for the treatment of GIST, and focuses on safety and tolerability of imatinib, with emphasis on common adverse events management and long term toxicity profile. EXPERT OPINION: Imatinib has been the standard of care for metastatic GIST and probably will continue to be so for the next few years. Still, despite dramatic responses initially, imatinib drug resistance continues to be the major factor for treatment discontinuation. The toxicity profile of imatinib has been well characterized, and although the majority of patients experience an adverse event during treatment with imatinib, these side effects are usually mild and manageable, with the majority of patients continuing treatment uninterruptedly. Early concerns regarding imatinib related cardiotoxicity in GIST have not been confirmed in large prospective randomized trials, with reports indicating a low incidence of approximately 0.2%-0.4%. Future strategies for treatment of imatinib resistant GIST will probably include novel tyrosine kinase inhibitors, combination therapies or immunotherapy. PMID- 26865351 TI - Titanium Dioxide Photocatalytic Polymerization of Acrylamide for Gel Electrophoresis (TIPPAGE) of Proteins and Structural Identification by Mass Spectrometry. AB - Polyacrylamide gel electrophoresis (PAGE) coupled with mass spectrometry has been well established for separating, identifying and quantifying protein mixtures from cell lines, tissues or other biological samples. The copolymerization process of acrylamide and bis-acrylamide is the key to mastering this powerful technique. In general, this is a vinyl addition reaction initiated by free radical-generating reagents such as ammonium persulfate (APS) and tetramethylethylenediamine (TEMED) under basic pH and degassing experimental condition. We report herein a photocatalytic polymerization approach that is based on photo-generated hydroxyl radicals with nanoparticles of titanium dioxide. It was shown that the polymerization process is greatly accelerated in acidic condition when ultraviolet light shots on the gel solution containing TiO2 nanoparticles without degassing. This feature makes it very useful in preparing Triton X-100 acid urea (TAU) gel that has been developed for separating basic proteins such as histones and variants in acidic experimental condition. Additionally, the presence of titanium dioxide in the gel not only improves mechanistic property of gels but also changes the migration pattern of different proteins that have different affinities to titanium dioxide. PMID- 26865353 TI - Pathologic mandibular fracture after biting crab shells following ramal bone graft. AB - The mandibular ramus is considered an appropriate choice for reconstruction of maxillofacial defects because of sufficient amounts of material and fewer donor site complications. Although bone harvesting from the mandibular ramus has many advantages, in rare cases it can result in pathologic fracture of the mandible. Here, we present a case of 59-year-old man who suffered a pathologic mandible fracture related to biting hard foods, such as crab shells, after a sinus bone lifting with ramal bone graft procedure performed 2 weeks prior. He underwent closed reduction by intermaxillary fixation with an arch bar over the course of 4 weeks. Three months later, the patients had a stable occlusion with normal mouth opening and sensation. To prevent this complication, the osteotomy should be performed in such a way that it is not too vertical during ramal bone harvesting. Furthermore, we wish to emphasize the importance of patients being instructed to avoid chewing hard foods for at least 4 weeks after ramal bone harvesting. PMID- 26865354 TI - Enhancement of umami taste of hydrolyzed protein from wheat gluten by beta cyclodextrin. AB - BACKGROUND: Wheat gluten was hydrolyzed by Flavourzyme and Neutrase at pH 7.0 and 50 degrees C for 8 h with beta-cyclodextrin (beta-CD) employed in the reaction. The hydrolysates were enzyme deactivated, cooled and centrifuged at 1500 * g for 15 min. RESULTS: Sensory and chemical characterization of wheat gluten hydrolysates WGH-1 (reaction conducted without beta-CD), WGH-2 (reaction conducted with beta-CD) and WGH-3 (beta-CD added to WGH-1) was performed. WGH-2 revealed enhanced umami taste and higher hydrolyzing degree, total free amino acid amount, protein yield and umami taste amino acid (Glu + Asp) amount. High performance liquid chromatography showed that the proportion of molecular weight 180-500 Da in WGH-2 was 11.5% higher than that in WGH-1. Further research indicated that beta-CD had multiple effects on the hydrolysis. It could not only increase the solubility of wheat gluten but also form inclusion complexes with resultants. This can both promote the hydrolysis and protect oligopeptides from degradation. CONCLUSION: beta-CD was found to have the ability to increase the umami taste of enzyme-hydrolyzed vegetable protein from wheat gluten. The reasons analyzed were that beta-CD could take part in the hydrolysis process by improving the solubility of wheat gluten and form inclusion complexes with resultants. (c) 2016 Society of Chemical Industry. PMID- 26865355 TI - Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist. AB - Intertumor heterogeneity, defined as the spectrum of morphological differences found in similar tumors in different patients, is a well-known event for pathologists. However, recent molecular studies have pointed to intratumor heterogeneity as one of the most important issues in human neoplasia in the next years. Clear cell renal cell carcinoma is an example of an intrinsically heterogeneous neoplasm, and some of the most salient advances in the knowledge of intratumor heterogeneity have been developed on it. This review intends to analyze this phenomenon in this tumor from the practicing pathologist's point of view. A careful study of the surgical specimen and an exhaustive tumor sampling are mandatory to keep relevant information. Currently accepted protocols designed for renal tumor sampling may be insufficient. As a result, a different approach to tumor sampling is advisable to ascertain that intratumor heterogeneity, if present, will be well represented in the selected material. PMID- 26865357 TI - Barriers to Eating Traditional Foods Vary by Age Group in Ecuador With Biodiversity Loss as a Key Issue. AB - OBJECTIVE: To document the perceptions of indigenous peoples for the sustainable management of natural resources against malnutrition. DESIGN: Initially 4 and then 12 interviews were conducted with 4 different age groups. SETTING: Eight rural villages in Guasaganda, central Ecuador, were studied in 2011-2012. PARTICIPANTS: A total of 75 people (22 children, 18 adolescents, 20 adults, and 15 elders). MAIN OUTCOME MEASURES: Benefits, severity, susceptibility, barriers, cues to action, and self-efficacy of eating traditional foods. ANALYSIS: Qualitative content analysis was completed using NVivo software. Initial analysis was inductive, followed by a content analysis directed by the Health Belief Model. Coding was completed independently by 2 researchers and kappa statistics (kappa >= 0.65) were used to evaluate agreement. RESULTS: Healthy perceptions toward traditional foods existed and differed by age. Local young people ate traditional foods for their health benefits and good taste; adults cultivated traditional foods that had an economic benefit. Traditional knowledge used for consumption and cultivation of traditional foods was present but needs to be disseminated. CONCLUSIONS AND IMPLICATIONS: Nutrition education in schools is needed that supports traditional knowledge in younger groups and prevents dietary changes toward unhealthy eating. Increased production of traditional food is needed to address current economic realities. PMID- 26865356 TI - Children's school-breakfast reports and school-lunch reports (in 24-h dietary recalls): conventional and reporting-error-sensitive measures show inconsistent accuracy results for retention interval and breakfast location. AB - Validation-study data were analysed to investigate retention interval (RI) and prompt effects on the accuracy of fourth-grade children's reports of school breakfast and school-lunch (in 24-h recalls), and the accuracy of school breakfast reports by breakfast location (classroom; cafeteria). Randomly selected fourth-grade children at ten schools in four districts were observed eating school-provided breakfast and lunch, and were interviewed under one of eight conditions created by crossing two RIs ('short'--prior-24-hour recall obtained in the afternoon and 'long'--previous-day recall obtained in the morning) with four prompts ('forward'--distant to recent, 'meal name'--breakfast, etc., 'open'--no instructions, and 'reverse'--recent to distant). Each condition had sixty children (half were girls). Of 480 children, 355 and 409 reported meals satisfying criteria for reports of school-breakfast and school-lunch, respectively. For breakfast and lunch separately, a conventional measure--report rate--and reporting-error-sensitive measures--correspondence rate and inflation ratio--were calculated for energy per meal-reporting child. Correspondence rate and inflation ratio--but not report rate--showed better accuracy for school breakfast and school-lunch reports with the short RI than with the long RI; this pattern was not found for some prompts for each sex. Correspondence rate and inflation ratio showed better school-breakfast report accuracy for the classroom than for cafeteria location for each prompt, but report rate showed the opposite. For each RI, correspondence rate and inflation ratio showed better accuracy for lunch than for breakfast, but report rate showed the opposite. When choosing RI and prompts for recalls, researchers and practitioners should select a short RI to maximise accuracy. Recommendations for prompt selections are less clear. As report rates distort validation-study accuracy conclusions, reporting-error sensitive measures are recommended. PMID- 26865359 TI - Ultrafast double-quantum NMR spectroscopy with optimized sensitivity for the analysis of mixtures. AB - Ultrafast (UF) 2D NMR enables the acquisition of 2D spectra within a single-scan. This methodology has become a powerful analytical tool, used in a large array of applications. However, UF NMR spectroscopy still suffers from the need to compromise between sensitivity, spectral width and resolution. With the commonly used UF-COSY pulse sequence, resolution issues are compounded by the presence of strong auto-correlation signals, particularly in the case of samples with high dynamic ranges. The recently proposed concept of UF Double Quantum Spectroscopy (DQS) allows a better peak separation as it provides a lower spectral peak density. This paper presents the detailed investigation of this new NMR tool in an analytical chemistry context. Theoretical calculations and numerical simulations are used to characterize the modulation of peak intensities as a function of pulse-sequence parameters, and thus enable a significant enhancement of the sensitivity. The analytical comparison of UF-COSY and UF-DQS shows similar performances, however the ultrafast implementation of the DQS approach is found to have some sensitivity advantages over its conventional counterpart. The analytical performance of the pulse sequence is illustrated by the quantification of taurine in complex mixtures (homemade and commercial energy drinks). The results demonstrate the high potential of this experiment, which forms a valuable alternative to UF-COSY spectra when the latter are characterized by strong overlaps and high dynamic ranges. PMID- 26865358 TI - Perceived Social Support From Friends and Parents for Eating Behavior and Diet Quality Among Low-Income, Urban, Minority Youth. AB - OBJECTIVE: Evidence of associations between social support and dietary intake among adolescents is mixed. This study examines relationships between social support for healthy and unhealthy eating from friends and parents, and associations with diet quality. DESIGN: Cross-sectional analysis of survey data. SETTING: Baltimore, MD. PARTICIPANTS: 296 youth aged 9-15 years, 53% female, 91% African American, participating in the B'More Healthy Communities for Kids study. MAIN OUTCOME MEASURE(S): Primary dependent variable: diet quality measured using Healthy Eating Index 2010 (HEI) overall score, calculated from the Block Kids Food Frequency Questionnaire. INDEPENDENT VARIABLES: Social support from parents and friends for healthy eating (4 questions analyzed as a scale) and unhealthy eating (3 questions analyzed individually), age, gender, race, and household income, reported via questionnaire. ANALYSIS: Adjusted multiple linear regressions (alpha, P < .05). RESULTS: Friend and parent support for healthy eating did not have statistically significant relationships with overall HEI scores. Youth who reported their parents offering high-fat foods or sweets more frequently had lower overall HEI scores (beta = -1.65; SE = 0.52; 95% confidence interval, -2.66 to -0.63). CONCLUSIONS AND IMPLICATIONS: These results are novel and demonstrate the need for additional studies examining support for unhealthy eating. These preliminary findings may be relevant to researchers as they develop family-based nutrition interventions. PMID- 26865360 TI - Current advances in ligand design for inorganic positron emission tomography tracers 68Ga, 64Cu, 89Zr and 44Sc. AB - A key part of the development of metal based Positron Emission Tomography probes is the chelation of the radiometal. In this review the recent developments in the chelation of four positron emitting radiometals, 68Ga, 64Cu, 89Zr and 44Sc, are explored. The factors that effect the chelation of each radio metal and the ideal ligand system will be discussed with regards to high in vivo stability, complexation conditions, conjugation to targeting motifs and complexation kinetics. A series of cyclic, cross-bridged and acyclic ligands will be discussed, such as CP256 which forms stable complexes with 68Ga under mild conditions and PCB-TE2A which has been shown to form a highly stable complex with 64Cu. 89Zr and 44Sc have seen significant development in recent years with a number of chelates being applied to each metal - eight coordinate di-macrocyclic terephthalamide ligands were found to rapidly produce more stable complexes with 89Zr than the widely used DFO. PMID- 26865362 TI - The spiral of distrust: (Non-)cooperation in a repeated trust game is predicted by anger and individual differences in negative reciprocity orientation. AB - This study investigated state anger and individual differences in negative reciprocity orientation as predictors of individuals' willingness to cooperate with strangers. In order to observe real behaviour, we used a trust game that was played over six periods. In the trust game, a first player (sender) determines how much of a certain endowment she/he wants to share with a second player (trustee), who then can give something back. We varied whether participants received feedback [feedback (yes, no)] about the trustee's behavioural decision (amount sent back). Supporting our hypotheses, the results suggest that feedback compared with no feedback about the trustee's behaviour increased anger. Specifically, information about low back transfers triggered anger and non cooperation in return. Importantly, participants with a strong negative reciprocity orientation reported higher levels of anger and were less willing to cooperate with the trustee compared with those with low negative reciprocity orientation. Moreover, even when anger was low, individuals with a strong negative reciprocity orientation were less willing to cooperate compared with those with a low negative reciprocity orientation. Thus, negative reciprocity orientation seems to arouse a spiral of distrust. Theoretical and practical implications of these findings are discussed. PMID- 26865363 TI - Open data 5 years on: a case series of 12 freedom of information requests for regulatory data to the European Medicines Agency. AB - BACKGROUND: Clinical trial (and other) data from the European Medicines Agency (EMA) offers the best available opportunity to address the extensive reporting bias in pharmaceutical trial literature. Data are requested via freedom of information requests, but 5 years on, little is known about how the system is working. METHODS: Case series of 12 requests for regulatory data (clinical study reports and other regulatory data) relating to 29 different compounds. We logged start and end dates for correspondence with and data releases from the EMA, the need for additional correspondence and appeal of initial negative decisions, and inspected data releases for redaction. We measured: time from initial request to first substantive response from the EMA, to final decision from the EMA (in case of appeal), to initial receipt of documents, and to completion of request; number of data transmission batches generated; number of pages received for each request; average number of pages per batch over time (for releases in multiple batches); judgment as to whether the request was satisfied. RESULTS: We found great variability in time to receive an initial decision from the EMA (1 to 13 weeks). Additional correspondence with the EMA was necessary in 10 of 12 requests. Four of 12 were initially refused but 3 of 4 were allowed on appeal after 3 to 33 additional weeks. One request was denied despite appeal. Time to final decision was 1 to 43 weeks. We received data for 11 of 12 requests in 98 batches. While two requests remain outstanding as at June 2015 the remaining nine requests took a median 43 weeks to completion (range: 17 to 186 weeks). Despite redaction in 10 of 11 releases (mainly of researcher and participant identifying information), 8 requested were wholly satisfied. CONCLUSIONS: The EMA is the only regulator in the world that is routinely releasing original clinical trial data, but release can take considerable time to occur and often only after a lengthy correspondence. Given its importance for research and significance for transparency we suggest ways in which the process could be made more efficient. PMID- 26865361 TI - Stem/progenitor cells in endogenous repairing responses: new toolbox for the treatment of acute lung injury. AB - The repair of organs and tissues has stepped into a prospective era of regenerative medicine. However, basic research and clinical practice in the lung regeneration remains crawling. Owing to the complicated three dimensional structures and above 40 types of pulmonary cells, the regeneration of lung tissues becomes a great challenge. Compelling evidence has showed that distinct populations of intrapulmonary and extrapulmonary stem/progenitor cells can regenerate epithelia as well as endothelia in various parts of the respiratory tract. Recently, the discovery of human lung stem cells and their relevant studies has opened the door of hope again, which might put us on the path to repair our injured body parts, lungs on demand. Herein, we emphasized the role of endogenous and exogenous stem/progenitor cells in lungs as well as artificial tissue repair for the injured lungs, which constitute a marvelous toolbox for the treatment of acute lung injury. Finally, we further discussed the potential problems in the pulmonary remodeling and regeneration. PMID- 26865364 TI - Protective effect of Sheng-Mai Yin, a traditional Chinese preparation, against doxorubicin-induced cardiac toxicity in rats. AB - BACKGROUND: Sheng-Mai Yin (SMY), a modern Chinese formula based on Traditional Chinese Medicine theory, has been used to treat cardiovascular diseases in Eastern Asia. Our study focuses on the cardioprotection of SMY against doxorubicin (DOX)-induced cardiac toxicity in vivo. METHODS: Rats were injected with DOX (2.5 mg/kg) in six injections over a 2-week period. SMY was administrated intragastrically at the dose of 8.35, 16.7 and 33.4 g/kg, or 16.7 g/kg only twice a day concurrently with DOX for the 2-weeks. A series of assays were performed to detect the effects of SMY on: (i) heart weight index (HWI) and left ventricular mass index (LVMI); (ii) cardiac function; (iii) heart tissue morphology; (iv) the contents of carboxy terminal propeptide of procollagen typeI (PICP), amino terminal propeptide of procollagen type III (PSHNP), transforming growth factor-beta1 (TGF-beta1), B-type natriuretic peptide (BNP), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (INF-gamma) and interleukin 6 (IL-6) by ELISA; (v) the mRNA levels of TGF-beta1 and toll-like receptor-2 (TLR2); and (vi) protein level of TGF-beta1. RESULTS: Rats treated with SMY displayed the reductions of BNP and CK-MB increased by DOX in a dose-dependent manner. Moderate dose of SMY exhibited the correction for the increased HWI, LVMI, and the injured cardiac function, as well as the collagen accumulation. In addition, cardioprotection of SMY against DOX-induced cardiac toxicity was demonstrated by the reduction of myocardial fibrosis, characterized by the suppression of PICP, PSHNP and TGF-beta1, as well as the anti-inflammation and the regulation for cardiac immune microenvironment, characterized by the inhibition of TLR2, MCP-1, INF-gamma and IL-6. CONCLUSIONS: SMY may protect heart function through the restriction of myocardial fibrosis induced by DOX, which suggests the potentially therapeutic effect of SMY on DOX-induced cardiomyopathy. PMID- 26865366 TI - Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons. AB - Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68-91% from week 2 after AAV2-bFGF treatment and by 82-210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion. PMID- 26865367 TI - A Novel Test for Detecting SNP-SNP Interactions in Case-Only Trio Studies. AB - Epistasis plays a significant role in the genetic architecture of many complex phenotypes in model organisms. To date, there have been very few interactions replicated in human studies due in part to the multiple-hypothesis burden implicit in genome-wide tests of epistasis. Therefore, it is of paramount importance to develop the most powerful tests possible for detecting interactions. In this work we develop a new SNP-SNP interaction test for use in case-only trio studies called the trio correlation (TC) test. The TC test computes the expected joint distribution of marker pairs in offspring conditional on parental genotypes. This distribution is then incorporated into a standard 1 d.f. correlation test of interaction. We show via extensive simulations under a variety of disease models that our test substantially outperforms existing tests of interaction in case-only trio studies. We also demonstrate a bias in a previous case-only trio interaction test and identify its origin. Finally, we show that a previously proposed permutation scheme in trio studies mitigates the known biases of case-only tests in the presence of population stratification. We conclude that the TC test shows improved power to identify interactions in existing, as well as emerging, trio association studies. The method is publicly available at www.github.com/BrunildaBalliu/TrioEpi. PMID- 26865369 TI - Embryonic Stem Cells Cultured in Microfluidic Chambers Take Control of Their Fate by Producing Endogenous Signals Including LIF. AB - It is important to understand the role played by endogenous signals in shaping stem cell fate decisions to develop better culture systems and to improve understanding of development processes. In this study, we describe the behavior of mouse embryonic stem cells (mESCs) inside microfluidic chambers (microchambers) operated under conditions of minimal perfusion. mESCs inside microchambers formed colonies and expressed markers of pluripotency in the absence of feeders or pluripotency-inducing signals such as leukemia inhibitory factor (LIF), while mESCs in standard cultureware differentiated rapidly. In a series of experiments, we demonstrate that remarkable differences in stem cell phenotype are due to endogenous production of LIF and other growth factors brought upon by cultivation in confines of a microchamber in the absence of perfusion (dilution). At the protein level, mESCs produced ~140 times more LIF inside microchambers than under standard culture conditions. In addition, we demonstrate that pluripotent phenotype of stem cells could be degraded by increasing the height (volume) of the microchamber. Furthermore, we show that inhibition of LIF in microchambers, via the JAK/STAT3 pathway, leads to preferential differentiation into mesoderm that is driven by bone morphogenetic protein (BMP)-4. Collectively, we demonstrate for the first time that it is possible to design a cell culture system where stem cell fate is controlled solely by the endogenous signals. Our study may help shift the paradigm of stem cell cultivation away from relying on expensive exogenous molecules such as growth factors and toward designing culture chambers for harnessing endogenous signals. Stem Cells 2016;34:1501-1512. PMID- 26865368 TI - Kel1p Mediates Yeast Cell Fusion Through a Fus2p- and Cdc42p-Dependent Mechanism. AB - Cell fusion is ubiquitous among eukaryotes. Although little is known about the molecular mechanism, several proteins required for cell fusion in the yeast Saccharomyces cerevisiae have been identified. Fus2p, a key regulator of cell fusion, localizes to the shmoo tip in a highly regulated manner. C-terminal truncations of Fus2p cause mislocalization and fusion defects, which are suppressed by overexpression of Kel1p, a kelch-domain protein of unknown function previously implicated in cell fusion. We hypothesize that Fus2p mislocalization is caused by auto-inhibition, which is alleviated by Kel1p overexpression. Previous work showed that Fus2p localization is mediated by both Fus1p- and actin dependent pathways. We show that the C-terminal mutations mainly affect the actin dependent pathway. Suppression of the Fus2p localization defect by Kel1p is dependent upon Fus1p, showing that suppression does not bypass the normal pathway. Kel1p and a homolog, Kel2p, are required for efficient Fus2p localization, acting through the actin-dependent pathway. Although Kel1p overexpression can weakly suppress the mating defect of a FUS2 deletion, the magnitude of suppression is allele specific. Therefore, Kel1p augments, but does not bypass, Fus2p function. Fus2p mediates cell fusion by binding activated Cdc42p Although Kel1p overexpression suppresses a Cdc42p mutant that is defective for Fus2p binding, cell fusion remains dependent upon Fus2p These data suggest that Fus2p, Cdc42p, and Kel1p form a ternary complex, which is stabilized by Kel1p Supporting this hypothesis, Kel1p interacts with two domains of Fus2p, partially dependent on Cdc42p We conclude that Kel1p enhances the activity of Fus2p/Cdc42p in cell fusion. PMID- 26865370 TI - Designing Standardized and Optimized Surveys to Assess Invertebrate Biodiversity in Tropical Irrigated Rice Using Structured Inventory and Species Richness Models. AB - Insect pest management depends on simple, rapid, and reliable sampling methods that should also be standardized and optimized. We tested structured inventory, community characterization, and sampling optimization approaches on the invertebrate fauna of Philippine irrigated rice, undisrupted by pesticides, using seven field methods and species richness models. Canopy and floodwater invertebrates were intensively and repetitively sampled from 600 quadrats (~0.1 m(2) planar area) over dry and wet cropping seasons in one field at the International Rice Research Institute in the Philippines. In the canopy, pooled counts from D-Vac and plant dissections (PD) on the same rice hills ("absolute methodology") were compared with three other methods (i.e., FARMCOP, Blower-Vac, sweep-net), while, in the floodwater, the area collector ("absolute methodology") was compared with three other methods (i.e., FARMCOP, Blower-Vac, strainer-net). Overall, 25 and 50% of the observed richness of canopy and floodwater taxa, respectively, were caught by all four methods. Estimated inventory completeness for the canopy and floodwater averaged 82 and 98%, respectively, after all methods were pooled. To maximize observed richness, optimization results for the canopy recommended allocating the highest sampling effort to D-Vac and PD, followed by the Blower-Vac, whereas the area collector should be assigned the highest sampling effort in the floodwater, followed by the strainer-net or Blower Vac. Our results suggest that structured inventory and species richness models are useful tools for setting optimization criteria and stopping rules for sampling crop-invertebrate assemblages based on inventory completeness and for enabling more informative biodiversity comparisons. PMID- 26865374 TI - Monte Carlo Simulations of Glu-242 in Cytochrome c Oxidase. AB - Monte Carlo (MC) simulations of conformational changes and protonation of Glu 242, a key residue that shuttles protons in cytochrome c oxidase (CcO), are reported. Previous studies suggest that this residue may play a role of the valve of the enzyme proton pump. Here we examine how sensitive the results of simulations are to the computational method used. We applied both molecular mechanic (MM) and hybrid quantum mechanic:molecular mechanic (QM:MM) methods and find that the results are qualitatively different. The results indicate that the mechanism for proton gating in CcO is still an open issue. PMID- 26865365 TI - The human HSP70 family of chaperones: where do we stand? AB - The 70-kDa heat shock protein (HSP70) family of molecular chaperones represents one of the most ubiquitous classes of chaperones and is highly conserved in all organisms. Members of the HSP70 family control all aspects of cellular proteostasis such as nascent protein chain folding, protein import into organelles, recovering of proteins from aggregation, and assembly of multi protein complexes. These chaperones augment organismal survival and longevity in the face of proteotoxic stress by enhancing cell viability and facilitating protein damage repair. Extracellular HSP70s have a number of cytoprotective and immunomodulatory functions, the latter either in the context of facilitating the cross-presentation of immunogenic peptides via major histocompatibility complex (MHC) antigens or in the context of acting as "chaperokines" or stimulators of innate immune responses. Studies have linked the expression of HSP70s to several types of carcinoma, with Hsp70 expression being associated with therapeutic resistance, metastasis, and poor clinical outcome. In malignantly transformed cells, HSP70s protect cells from the proteotoxic stress associated with abnormally rapid proliferation, suppress cellular senescence, and confer resistance to stress-induced apoptosis including protection against cytostatic drugs and radiation therapy. All of the cellular activities of HSP70s depend on their adenosine-5'-triphosphate (ATP)-regulated ability to interact with exposed hydrophobic surfaces of proteins. ATP hydrolysis and adenosine diphosphate (ADP)/ATP exchange are key events for substrate binding and Hsp70 release during folding of nascent polypeptides. Several proteins that bind to distinct subdomains of Hsp70 and consequently modulate the activity of the chaperone have been identified as HSP70 co-chaperones. This review focuses on the regulation, function, and relevance of the molecular Hsp70 chaperone machinery to disease and its potential as a therapeutic target. PMID- 26865376 TI - Overexpression of ACC gene from oleaginous yeast Lipomyces starkeyi enhanced the lipid accumulation in Saccharomyces cerevisiae with increased levels of glycerol 3-phosphate substrates. AB - The conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase (ACC) is the rate-limiting step in fatty acid biosynthesis. In this study, a gene coding for ACC was isolated and characterized from an oleaginous yeast, Lipomyces starkeyi. Real-time quantitative PCR (qPCR) analysis of L. starkeyi acetyl-CoA carboxylase gene (LsACC1) showed that the expression levels were upregulated with the fast accumulation of lipids. The LsACC1 was co-overexpressed with the glycerol 3-phosphate dehydrogenase gene (GPD1), which regulates lipids biosynthesis by supplying another substrates glycerol 3-phosphate for storage lipid assembly, in the non-oleaginous yeast Saccharomyces cerevisiae. Further, the S. cerevisiae acetyl-CoA carboxylase (ScACC1) was transferred with GPD1 and its function was analyzed in comparison with LsACC1. The results showed that overexpressed LsACC1 and GPD1 resulted in a 63% increase in S. cerevisiae. This study gives new data in understanding of the molecular mechanisms underlying the regulation of fatty acids and lipid biosynthesis in yeasts. PMID- 26865377 TI - The effect of fluctuating maskers on speech understanding of high-performing cochlear implant users. AB - OBJECTIVE: The present study evaluated whether the poorer baseline performance of cochlear implant (CI) users or the technical and/or physiological properties of CI stimulation are responsible for the absence of masking release. DESIGN: This study measured speech reception thresholds (SRTs) in continuous and modulated noise as a function of signal to noise ratio (SNR). STUDY SAMPLE: A total of 24 subjects participated: 12 normal-hearing (NH) listeners and 12 subjects provided with recent MED-EL CI systems. RESULTS: The mean SRT of CI users in continuous noise was -3.0 +/- 1.5 dB SNR (mean +/- SEM), while the normal-hearing group reached -5.9 +/- 0.8 dB SNR. In modulated noise, the difference across groups increased considerably. For CI users, the mean SRT worsened to -1.4 +/- 2.3 dB SNR, while it improved for normal-hearing listeners to -18.9 +/- 3.8 dB SNR. CONCLUSIONS: The detrimental effect of fluctuating maskers on SRTs in CI users shown by prior studies was confirmed by the current study. Concluding, the absence of masking release is mainly caused by the technical and/or physiological properties of CI stimulation, not just the poorer baseline performance of many CI users compared to normal-hearing subjects. Speech understanding in modulated noise was more robust in CI users who had a relatively large electrical dynamic range. PMID- 26865379 TI - Secrets of Endometrial Receptivity: Some Are Hidden in Uterine Secretome. AB - PROBLEM: Endometrium, the innermost mucosal layer of the uterus, serves as a lodge for the embryo in eutherian mammals. The endometrium is constituted of various cell types, and each cell type executes specific functions to facilitate embryo implantation and development. It is well established that the endometrium, despite being non-permissive to the embryo for the major period of a menstrual cycle, is irreplaceable in the scheme of events essential for procreation. However, the embryo, before initiating physical contact with the endometrium, encounters the uterine cavity that remains bathed in uterine fluid. Uterine fluid is an admixture of endometrial secretions, plasma transudates, and oviductal fluid. Uterine fluid components are believed to play important roles in immunosuppression and embryo development during peri-implantation period. Uterine fluid is also involved in defense against pathogens, sperm migration, and lubrication of endometrium. The advent of high-throughput functional genomics tools has created enormous opportunities to investigate the uterine fluid for its protein repertoire and modulation during the receptive phase of an endometrial cycle in animals and humans. Towards this, few investigations have been conducted in recent years. The data obtained using non-targetted functional genomics approaches need to be assimilated with the existing information on specific components of uterine fluid. METHOD: This review compiles existing information on the composition of uterine fluid and its significance in endometrial functions and dysfunctions. RESULT: Collectively, investigations based on targetted and non targetted approaches have revealed the presence of several cytokines, growth factors, ions, carbohydrates, and steroids, in human uterine fluid. CONCLUSION: Detailed investigations of human uterine fluid, especially directed towards the elucidation of functional relevance of different proteins in uterine fluid, will help identify novel markers of endometrial receptivity and also gain significant insights into the mechanisms underlying unexplained infertility, recurrent pregnancy losses, and other endometrial pathologies. PMID- 26865380 TI - Improving Surgical Research by Involving Stakeholders. PMID- 26865378 TI - Noninvasive Monitoring of the Mitochondrial Function in Mesenchymal Stromal Cells. AB - PURPOSE: Mitochondria are a gatekeeper of cell survival and mitochondrial function can be used to monitor cell stress. Here we validate a pathway-specific reporter gene to noninvasively image the mitochondrial function of stem cells. PROCEDURES: We constructed a mitochondrial sensor with the firefly luciferase (Fluc) reporter gene driven by the NQO1 enzyme promoter. The sensor was introduced in stem cells and validated in vitro and in vivo, in a mouse model of myocardial ischemia/reperfusion (IR). RESULTS: The sensor activity showed an inverse relationship with mitochondrial function (R (2) = -0.975, p = 0.025) and showed specificity and sensitivity for mitochondrial dysfunction. In vivo, NQO1 Fluc activity was significantly higher in IR animals vs. controls, indicative of mitochondrial dysfunction, and was corroborated by ex vivo luminometry. CONCLUSIONS: Reporter gene imaging allows assessment of the biology of transplanted mesenchymal stromal cells (MSCs), providing important information that can be used to improve the phenotype and survival of transplanted stem cells. PMID- 26865381 TI - Chemically Stable Covalent Organic Framework (COF)-Polybenzimidazole Hybrid Membranes: Enhanced Gas Separation through Pore Modulation. AB - Highly flexible, TpPa-1@PBI-BuI and TpBD@PBI-BuI hybrid membranes based on chemically stable covalent organic frameworks (COFs) could be obtained with the polymer. The loading obtained was substantially higher (50 %) than generally observed with MOFs. These hybrid membranes show an exciting enhancement in permeability (about sevenfold) with appreciable separation factors for CO2/N2 and CO2/CH4. Further, we found that with COF pore modulation, the gas permeability can be systematically enhanced. PMID- 26865383 TI - Distribution of the two-sample t-test statistic following blinded sample size re estimation. AB - We consider the blinded sample size re-estimation based on the simple one-sample variance estimator at an interim analysis. We characterize the exact distribution of the standard two-sample t-test statistic at the final analysis. We describe a simulation algorithm for the evaluation of the probability of rejecting the null hypothesis at given treatment effect. We compare the blinded sample size re estimation method with two unblinded methods with respect to the empirical type I error, the empirical power, and the empirical distribution of the standard deviation estimator and final sample size. We characterize the type I error inflation across the range of standardized non-inferiority margin for non inferiority trials, and derive the adjusted significance level to ensure type I error control for given sample size of the internal pilot study. We show that the adjusted significance level increases as the sample size of the internal pilot study increases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26865382 TI - Race-Specific Pharmacodynamic Model of Propofol-Induced Loss of Consciousness. AB - We present a race-specific model of propofol-induced loss of consciousness that is based on pharmacodynamic data collected and adapted from the peer-reviewed literature. In the proposed race-specific model that includes EC05 and EC95 concentrations, the median (EC50) (and where available 95%CI) propofol concentrations at the effect site compartment for propofol-induced loss of consciousness for whites, Chinese, blacks, and Indians are 2.8 (2.7-2.9), 2.2 (2.2-2.3), 2.0, and 1.9 MUg/mL, respectively. PMID- 26865384 TI - Ultrapure Blue Thermally Activated Delayed Fluorescence Molecules: Efficient HOMO LUMO Separation by the Multiple Resonance Effect. AB - Ultrapure blue-fluorescent molecules based on thermally activated delayed fluorescence are developed. Organic light-emitting diode (OLED) devices employing the new emitters exhibit a deep blue emission at 467 nm with a full-width at half maximum of 28 nm, CIE coordinates of (0.12, 0.13), and an internal quantum efficiency of ~100%, which represent record-setting performance for blue OLED devices. PMID- 26865375 TI - Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease. AB - Dopamine-releasing neurons within the Substantia nigra (SN DA) are particularly vulnerable to degeneration compared to other dopaminergic neurons. The age dependent, progressive loss of these neurons is a pathological hallmark of Parkinson's disease (PD), as the resulting loss of striatal dopamine causes its major movement-related symptoms. SN DA neurons release dopamine from their axonal terminals within the dorsal striatum, and also from their cell bodies and dendrites within the midbrain in a calcium- and activity-dependent manner. Their intrinsically generated and metabolically challenging activity is created and modulated by the orchestrated function of different ion channels and dopamine D2 autoreceptors. Here, we review increasing evidence that the mechanisms that control activity patterns and calcium homeostasis of SN DA neurons are not only crucial for their dopamine release within a physiological range but also modulate their mitochondrial and lysosomal activity, their metabolic stress levels, and their vulnerability to degeneration in PD. Indeed, impaired calcium homeostasis, lysosomal and mitochondrial dysfunction, and metabolic stress in SN DA neurons represent central converging trigger factors for idiopathic and familial PD. We summarize double-edged roles of ion channels, activity patterns, calcium homeostasis, and related feedback/feed-forward signaling mechanisms in SN DA neurons for maintaining and modulating their physiological function, but also for contributing to their vulnerability in PD-paradigms. We focus on the emerging roles of maintained neuronal activity and calcium homeostasis within a physiological bandwidth, and its modulation by PD-triggers, as well as on bidirectional functions of voltage-gated L-type calcium channels and metabolically gated ATP-sensitive potassium (K-ATP) channels, and their probable interplay in health and PD. We propose that SN DA neurons possess several feedback and feed-forward mechanisms to protect and adapt their activity-pattern and calcium-homeostasis within a physiological bandwidth, and that PD-trigger factors can narrow this bandwidth. We summarize roles of ion channels in this view, and findings documenting that both, reduced as well as elevated activity and associated calcium-levels can trigger SN DA degeneration. This article is part of a special issue on Parkinson disease. PMID- 26865385 TI - An avian-only Filippov model incorporating culling of both susceptible and infected birds in combating avian influenza. AB - Depopulation of birds has always been an effective method not only to control the transmission of avian influenza in bird populations but also to eliminate influenza viruses. We introduce a Filippov avian-only model with culling of susceptible and/or infected birds. For each susceptible threshold level [Formula: see text], we derive the phase portrait for the dynamical system as we vary the infected threshold level [Formula: see text], focusing on the existence of endemic states; the endemic states are represented by real equilibria, pseudoequilibria and pseudo-attractors. We show generically that all solutions of this model will approach one of the endemic states. Our results suggest that the spread of avian influenza in bird populations is tolerable if the trajectories converge to the equilibrium point that lies in the region below the threshold level [Formula: see text] or if they converge to one of the pseudoequilibria or a pseudo-attractor on the surface of discontinuity. However, we have to cull birds whenever the solution of this model converges to an equilibrium point that lies in the region above the threshold level [Formula: see text] in order to control the outbreak. Hence a good threshold policy is required to combat bird flu successfully and to prevent overkilling birds. PMID- 26865386 TI - Core Competencies in Geriatric Dentistry Fellowship Programs: a Delphi Study. AB - PURPOSE/OBJECTIVES: The healthcare workforce is challenged with preparing for the increasing number of older persons and complexities of their healthcare needs. Fellowship trained geriatric dentists are charged with the task of addressing the dental needs of this vastly growing cohort.The purpose of this study is to formulate a set of competencies for Geriatric Dental Fellowship Training Programs. METHODS: The Delphi technique-a series of three rounds of anonymous questionnaires to obtain the opinions of experts without bringing them together. RESULTS: In Round 1, we proposed 45 competencies based on findings in previous literature. In Round 2, there were 19 respondents whose edits narrowed our list to 39 competencies proposed by the participants. In Round 3, based on group consensus we formulated a final list of 42 competencies. CONCLUSION: Utilizing the Delphi process, a panel of geriatric dental experts identified a set of core competencies for curriculums in dental fellowship programs. PMID- 26865387 TI - Downregulation of IDH2 exacerbates H2O2-mediated cell death and hypertrophy. AB - OBJECTIVES: Reactive oxygen species-mediated cell death contributes to the pathophysiology of cardiovascular disease and myocardial dysfunction. We recently showed that mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) functions as an antioxidant and anti-apoptotic protein by supplying NADPH to antioxidant systems. METHODS: In the present study, we demonstrated that H2O2 induced apoptosis and hypertrophy of H9c2 cardiomyoblasts was markedly exacerbated by small interfering RNA (siRNA) specific for IDH2. RESULTS: Attenuated IDH2 expression resulted in the modulation of cellular and mitochondrial redox status, mitochondrial function, and cellular oxidative damage. MitoTEMPO, a mitochondria-targeted antioxidant, efficiently suppressed increased caspase-3 activity, increased cell size, and depletion of cellular GSH levels in IDH2 siRNA-transfected cells that were treated with H2O2. DISCUSSION: These results indicated that the disruption of cellular redox balance might be responsible for the enhanced H2O2-induced apoptosis and hypertrophy of cultured cardiomyocytes by the attenuated IDH2 expression. PMID- 26865389 TI - California doctor convicted of murder in overdose deaths is sentenced to 30 years. PMID- 26865388 TI - Intrafamily and Interfamilial Phenotype Variation and Immature Immunity in Patients With Netherton Syndrome and Finnish SPINK5 Founder Mutation. AB - IMPORTANCE: Netherton syndrome (NS) is a rare and severe genodermatosis caused by SPINK5 mutations leading to the loss of lymphoepithelial Kazal-type-related inhibitor (LEKTI). Netherton syndrome is characterized by neonatal scaling erythroderma, a bamboolike hair defect, a substantial skin barrier defect, and a profound atopic diathesis. Netherton syndrome has been proposed to be a primary immunodeficiency syndrome because of the high frequency of infections. The precise mechanisms underlying the disease are not fully understood. OBJECTIVE: To study the association of the SPINK5 mutation with the NS phenotype and the extent of immunologic deficiencies in NS. DESIGN, SETTING, AND PARTICIPANTS: Relevant tissue samples and follow-up data from 11 patients with NS from 7 families, including 3 multiplex families, were collected, constituting all known patients with NS in Finland. Another patient with NS from a neighboring country was included. Data were collected from August 10, 2011, to February 20, 2015. SPINK5 mutations were sequenced, and thorough clinical evaluation and histopathologic and immunohistochemical evaluations of skin samples were performed. The function of natural killer cells, lymphocyte phenotype, and serum immunoglobulin subclass levels were evaluated. Data analysis was conducted from October 19, 2011, to February 20, 2015. MAIN OUTCOMES AND MEASURES: The nature of SPINK5 mutations and their correlation with phenotypes in Finnish patients with NS, intrafamilial phenotype variations, and the type of immunologic defects in NS were evaluated. RESULTS: Among the 11 Finnish patients with NS (8 male [73%]; 3 female [27%]; mean [SD] age, 30.1 [9.1] years), a Finnish founder mutation c.652C>T (p.Arg218*) in SPINK5 was identified in 10 patients from 6 families who all originated from the same region. Eight patients were homozygotes for this mutation and 2 siblings were compound heterozygotes with a splice site mutation c.1220 + 1G>C (IVS13 + 1 G>C). Phenotypes were comparable, but some intrafamilial and interfamilial variations were noted. Compound heterozygous patients had a milder phenotype and showed residual LEKTI expression. A previously unreported c.1772delT (p.Leu591Glnfs124*) mutation was found in 1 patient with a phenotype similar to the patients homozygous for the founder mutation. The patient from the neighboring country had a distinct phenotype and different mutations. Immunologically, natural killer cells had an immature phenotype and impaired cytotoxicity and degranulation, levels of memory B cells were reduced, and serum IgG4 levels were elevated. Intravenous immunoglobulin treatment has been beneficial in 1 patient with NS. CONCLUSIONS AND RELEVANCE: This report discloses a prevalent SPINK5 founder mutation in Finland and illustrates NS phenotype variability. Our results also point to a possible role of immature immunity in the frequent infections seen in NS. PMID- 26865390 TI - Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3-1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects. AB - BACKGROUND: BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported. SUBJECTS AND METHODS: In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (i.v.) infusion of BTH1677 at 0.5, 1, 2, 4, or 6 mg/kg or placebo, respectively. In the Phase 1b multi-dosing study, subjects were randomized (3:1 per cohort) to 7 daily i.v. infusions of BTH1677 at 1, 2, or 4 mg/kg or placebo, respectively. Safety and PK non compartmental analyses were performed. RESULTS: Thirty-six subjects (N = 24 Phase 1a; N = 12 Phase 1b) were randomized to treatment. No deaths or serious adverse events occurred in either study. Mild or moderate adverse events (AEs) occurred in 67% of BTH1677-treated subjects in both studies. Treatment-related AEs (occurring in >=10% of subjects) included dyspnea, flushing, headache, nausea, paraesthesia, and rash in Phase 1a and conjunctivitis and headache in Phase 1b. BTH1677 serum concentration was linear with dose. Clearance, serum elimination half-life (t1/2) and volume of distribution (Vss) were BTH1677 dose-independent. In Phase 1b, area under the curve, t1/2, and Vss values were larger at steady state on days 6-30 versus day 0. CONCLUSIONS: BTH1677 was well tolerated after single doses up to 6 mg/kg and after 7 daily doses up to 4 mg/kg. PMID- 26865391 TI - Comparison of different anthropometric measures in the adult population in Serbia as indicators of obesity: data from the National Health Survey 2013. AB - OBJECTIVE: The present study aimed to compare different indicators of obesity in the Serbian adult population. DESIGN: Cross-sectional study. A stratified, two stage, national-representative random sampling approach was used for the selection of the survey sample. Data sources were questionnaires created according to the European Health Interview Survey questionnaire. Measurements of weight, height and waist circumference (WC) were performed using standard procedures. Anthropometric measures included BMI, WC and waist-to-height ratio (WHtR). SETTING: Data for the study were obtained from the 2013 National Health Survey, performed in line with the EUROSTAT recommendations for performance of the European Health Interview Survey. SUBJECTS: Adults aged >=20 years. RESULTS: According to BMI, out of the whole studied population (12 460 adults of both sexes) 2.4 % were underweight, 36.4 % overweight and 22.4 % obese. Using WC and WHtR as measures of adiposity showed that 22.5 % and 42.8 % of participants were overweight and 39.8 % and 25.3 % were obese, respectively. Men and women differed significantly in all variables observed. Overweight was more frequent in men and obesity in women regardless of adiposity measure used. CONCLUSIONS: In spite of strong correlations between BMI, WC and WHtR, substantial discrepancies between these three measures in the assessment of overweight and obesity were found, especially in some age groups. Which of these anthropometric measures should be used, or whether two or all three of them should be applied, depends on their associations with cardiovascular or some other disease of interest. PMID- 26865393 TI - Tuning the surface electronic structure of a Pt3Ti(111) electro catalyst. AB - Increasing the efficiency and stability of bimetallic electro catalysts is particularly important for future clean energy technologies. However, the relationship between the surface termination of these alloys and their catalytic activity is poorly understood. Therefore, we report on fundamental UHV-SPM, LEED, and DFT calculations of the Pt3Ti(111) single crystal surface. Using voltage dependent imaging the surface termination of Pt3Ti(111) was studied with atomic resolution. Combining these images with simulated STM maps based on ab initio DFT calculations allowed us to identify the three upper layers of the Pt3Ti(111) single crystal and their influence upon the surface electronic structure. Our results show that small changes in the composition of the second and third atomic layer are of significant influence upon the surface electronic structure of the Pt3Ti electro catalyst. Furthermore, we provide relevant insights into the dependence of the surface termination on the preparation conditions. PMID- 26865392 TI - Health resource utilisation associated with skeletal-related events in patients with bone metastases secondary to solid tumours: regional comparisons in an observational study. AB - Skeletal-related events (SREs) including spinal cord compression, pathologic fracture, and radiation or surgery to bone, occur frequently due to bone metastases in advanced cancer. This analysis of a multicentre, observational study was designed to describe cross-regional differences in health resource utilisation (HRU) of SREs in Western Europe and the US. Patients with bone metastases due to breast, lung or prostate cancer, or multiple myeloma who had experienced a SRE within the past 97 days were enrolled. Investigators recorded HRU associated with SREs, including hospitalisation and length of stay (LOS), outpatient visits, procedures and bisphosphonate use. This subanalysis includes 668 patients with solid tumours (US, n = 190 with 354 SREs; EU, n = 478 with 893 SREs). The rate of SREs associated with hospitalisation(s) was higher in the EU vs. the US (30% vs. 15%, P < 0.001) and LOS was longer in the EU [mean (SD) days/SRE: 19.87 (17.31) vs. 10.61 (9.39)]. However, the US was associated with higher rate of SREs with outpatient visits than the EU (88% vs. 74%, P < 0.0001) and more procedures [mean (SD)/SRE: 11.26 (7.94) vs. 6.91 (6.48)]. Bisphosphonates were less often used in the EU (65% vs. 76% of US, P = 0.0033). In patients experiencing SREs due to bone metastases, HRU patterns reflect regional diversity with a substantial burden in both regions. PMID- 26865394 TI - Nitric oxide-induced autophagy and the activation of activated protein kinase pathway protect against apoptosis in human dental pulp cells. AB - AIM: To investigate the role of nitric oxide (NO)-induced autophagy in human dental pulp cells (HDPCs) and the involvement of AMP-activated protein kinase (AMPK) pathway. METHODOLOGY: The MTT assay was used to determine the cytotoxic effect of the NO donor sodium nitroprusside (SNP) in HDPCs. Apoptosis was detected by means of the terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and apoptosis- or autophagy-related signal molecules were observed by Western blot analysis. Acidic autophagolysosomal vacuoles were stained with acridine orange to detect autophagy in the presence of 3 methyladenine (3MA) used to inhibit autophagy. To explore the mechanism underlying autophagy and its protective role against apoptosis, compound C, the chemical AMPK inhibitor, was used. Statistical analysis was performed using Student's t-test or analysis of variance (anova) followed by the Student-Newman Keuls test (P < 0.05). RESULTS: SNP decreased viability of the HDPCs in a dose- and time-dependent manner. Exposing the HDPCs to SNP increased the levels of p62 and LC3-II, the typical markers of autophagy, and increased the number of acidic autophagolysosomal vacuoles, indicating the appearance of autophagy as detected by acridine orange staining (P < 0.05). Pre-treatment with 3MA decreased cell viability but increased cleaved poly(ADP-ribose) polymerase (PARP) and caspase-3, apoptosis indicators, in the SNP-treated HDPCs (P < 0.05). SNP activated AMPK/ULK signalling, whilst the inhibition of AMPK by compound C enhanced apoptotic cell death induced by SNP in the HDPCs (P < 0.05). CONCLUSION: NO induced autophagy with AMPK activation, which plays a role in the survival of HDPCs against NO induced apoptosis. PMID- 26865395 TI - The Involvement of the Anterolateral Ligament in Rotational Control of the Knee. AB - BACKGROUND: Rotational control of the knee is crucial for knee stability. The anterolateral ligament (ALL) has been identified as a potentially important structure involved in rotational control of the knee. PURPOSE/HYPOTHESIS: The purpose of this study was to determine, utilizing a navigation system, the involvement of the anterior cruciate ligament (ACL), the iliotibial band (ITB), and the ALL in tibial internal rotational control of the knee. The hypothesis was that the ALL would be involved in rotational control of the knee at varying degrees of knee flexion. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve fresh-frozen cadaveric knees were tested in internal rotation at 20 degrees and 90 degrees of flexion and then subsequently tested using a simulated pivot-shift test consisting of coupled axial rotation at 30 degrees of flexion. Serial sectioning of the ACL, ALL, and ITB was performed. On the contralateral knee, sectioning was performed in the reverse order. Measurements were collected using a surgical navigation system before and after each sectioning. RESULTS: After ACL sectioning, an incision of the ALL induced a significant increase in internal rotation (+19.2% [P = .0002] at 20 degrees ; +21.8% [P = .0029] at 90 degrees ) and in coupled axial rotation (+43.0%; P = .0035) compared with the intact knee as well as a significant increase in internal rotation at 90 degrees (+13.4%; P = .009) and in coupled axial rotation (+30.8%; P = .0124) compared with the ACL-deficient knee. After ITB sectioning, an additional ALL section caused a significant increase in internal rotation (+39.0% [P = .002] at 20 degrees ; +63.0% [P = .0147] at 90 degrees ) and in coupled axial rotation (+59.7%; P = .0003) compared with the intact knee as well as a significant increase in internal rotation at 90 degrees (+14.8%; P = .0067) in comparison to the ITB-deficient knee. CONCLUSION: The ALL is involved in rotational control of the knee at varying degrees of knee flexion and during a simulated pivot shift. Concomitant to an ACL or ITB transection, sectioning the ALL further increased rotational laxity. CLINICAL RELEVANCE: This laboratory study demonstrated that the ALL provides rotational control of the knee in combination with the ACL and/or ITB. PMID- 26865396 TI - Reversibility of Supraspinatus Muscle Atrophy in Tendon-Bone Healing After Arthroscopic Rotator Cuff Repair. AB - BACKGROUND: To date, there are few reports of the definite reversibility of rotator cuff muscle atrophy after repair. PURPOSE: To evaluate the reversibility of rotator cuff muscle atrophy after successful arthroscopic repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Included in this study were 47 patients (mean age, 61.2 +/- 7.3 years; range, 49-73 years) who underwent arthroscopic rotator cuff repair as well as magnetic resonance imaging (MRI) preoperatively and at 6-month and last follow-up. Patients who had confirmed rotator cuff healing (grades 1-3 according to the Sugaya classification) on both series of postoperative MRI were enrolled in the study. The mean time from the onset of symptoms to surgery was 24.7 +/- 25.6 months (range, 3-120 months). The minimum follow-up was 2 years, and the mean follow-up duration was 41.8 +/- 14.4 months. Serial changes in the supraspinatus muscle area on the most matching MRI scans (sagittal-oblique view) were evaluated. The area was measured by 2 independent observers. RESULTS: Both independent observers reported no significant difference in the area of the supraspinatus muscle between the preoperative time point and 6-month follow-up (observer 1: P = .135; observer 2: P = .189). However, there was a significant difference between the 6-month and last follow-up (mean, 41.8 months; observers 1 and 2: P < .001). The serial changes in the area preoperatively and at 6-month and last follow-up were 419.41 +/- 122.97 mm(2), 431.76 +/- 104.27 mm(2), and 466.73 +/- 121.42 mm(2), respectively (observer 1), and 421.01 +/- 116.61 mm(2), 432.56 +/- 100.78 mm(2), and 469.84 +/- 113.80 mm(2), respectively (observer 2). The intraclass correlation coefficient between the 2 observers was 0.988. At final follow-up, the area increase on the medial and lateral aspects of the sagittal-oblique view compared with preoperatively was 13.9% (P < .001) and 11.3% (P < .001), respectively. Fatty infiltration did not change from preoperatively to 6-month follow-up (P > .999) or from 6-month to final follow-up (P = .077). CONCLUSION: After successful arthroscopic rotator cuff repair, there was a slight (11.3% 13.9%) increase in muscle volume from preoperatively to final follow-up, as seen on serial MRI. Fatty infiltration according to the Goutallier grade was not reversed (P = .077). Some reversibility of supraspinatus muscle atrophy may exist in tendon-bone healing after arthroscopic rotator cuff repair; further follow-up is needed to better elucidate this result. PMID- 26865397 TI - Arthroscopic Implant-Free Bone Grafting for Shoulder Instability With Glenoid Bone Loss: Clinical and Radiological Outcome at a Minimum 2-Year Follow-up. AB - BACKGROUND: Posttraumatic anteroinferior shoulder dislocations with concomitant glenoid bone loss show high recurrence rates. The open J-bone graft technique for implant-less anatomic restoration of bony glenoid structure has previously been described, whereas results of arthroscopic techniques are currently not available. PURPOSE: To evaluate clinical and radiological outcome after arthroscopic anatomic reconstruction of the glenoid for recurrent anteroinferior glenohumeral instability. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fifteen shoulders of 14 patients with recurrent anteroinferior shoulder instability were prospectively followed after glenoid reconstruction with a modified arthroscopic, implant-free J-bone graft. Preoperatively, the instability severity index score was documented. Patients were followed for a minimum of 2 years using the Rowe score and the Constant score. Subjective outcome was assessed using a visual analog scale (VAS) for pain and the subjective shoulder value for sports (SSVS); satisfaction with procedure outcome was also rated. Range of motion was recorded. Incidence of recurrent instability, defined as dislocation, subluxation, or persistent apprehensiveness, was documented. Pre- and postoperative (1 day and 3, 12, and 24 months) computed tomographic images were used to evaluate glenoid bone loss, reconstruction of the glenoid, and graft remodeling. RESULTS: All preoperative scores (Rowe score: 57.6 +/- 14.4; Constant score: 70.9 +/- 8.9; VAS: 4.4 +/- 2.6; SSVS: 31.4% +/- 19.5%) were significantly (P <= .02) improved at final follow-up (Rowe score: 98.6 +/- 1.5; Constant score: 96.3 +/- 3.9; VAS: 0.2 +/- 0.6; SSVS: 95.6% +/- 3.8%). The preoperative glenoid area (82.1% +/- 4.5%) was significantly increased immediately after surgery to 99.2% +/- 6.6% (P < .001). After a physiological remodeling process, the glenoid area remained significantly increased at the latest follow-up (89.5 +/- 3.2%, P < .001). J-bone grafting successfully restored glenoid concavity by significantly increasing concavity extent and depth from preoperative (19.8 +/- 2.1 and 0.9 +/- 0.6 mm, respectively) to postoperative (24.0 +/- 2.1 and 2.1 +/- 0.8 mm, respectively) (P < .001). There were no recurrent instabilities. One traumatic graft fracture occurred during the follow-up period. CONCLUSION: The arthroscopic J-bone graft technique permits minimally invasive reconstruction of anteroinferior glenoid defects and provided excellent early clinical outcome without recurrent instability in posttraumatic shoulder dislocations. A physiological remodeling process leads to restoration of a more natural glenoid anatomy. PMID- 26865399 TI - Addition of low concentrations of an ionic liquid to a base oil reduces friction over multiple length scales: a combined nano- and macrotribology investigation. AB - The efficacy of ionic liquids (ILs) as lubricant additives to a model base oil has been probed at the nanoscale and macroscale as a function of IL concentration using the same materials. Silica surfaces lubricated with mixtures of the IL trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate and hexadecane are probed using atomic force microscopy (AFM) (nanoscale) and ball-on disc tribometer (macroscale). At both length scales the pure IL is a much more effective lubricant than hexadecane. At the nanoscale, 2.0 mol% IL (and above) in hexadecane lubricates the silica as well as the pure IL due to the formation of a robust IL boundary layer that separates the sliding surfaces. At the macroscale the lubrication is highly load dependent; at low loads all the mixtures lubricate as effectively as the pure IL, whereas at higher loads rather high concentrations are required to provide IL like lubrication. Wear is also pronounced at high loads, for all cases except the pure IL, and a tribofilm is formed. Together, the nano- and macroscales results reveal that the IL is an effective lubricant additive - it reduces friction - in both the boundary regime at the nanoscale and mixed regime at the macroscale. PMID- 26865400 TI - Pyrone Diels-Alder Routes to Indolines and Hydroindolines: Syntheses of Gracilamine, Mesembrine, and Delta(7) -Mesembrenone. AB - Although the Diels-Alder reaction has long been utilized for the preparation of numerous heterocycles, opportunities to extend its power remain. Herein, we detail a simple, modular, and robust approach that combines various amines regioselectively with 4,6-dichloropyrone to create substrates which, under appropriate conditions, can directly deliver varied indolines and hydroindolines through [4+2] cycloadditions with substitution patterns difficult to access otherwise. As an initial demonstration of the power of the strategy, several different natural products have been obtained either formally or by direct total synthesis, with efforts toward one of these-the complex amaryllidaceae alkaloid gracilamine-affording the shortest route to date in terms of linear step count. PMID- 26865398 TI - Physiological Dysregulation, Frailty, and Risk of Mortality Among Older Adults. AB - This study examines whether frailty is associated with mortality independently of physiological dysregulation (PD) and, if so, which is the more accurate predictor of survival. Data come from the Social Environment and Biomarkers of Aging Study. We use Cox proportional hazard models to test the associations between PD, frailty, and 4- to 5-year survival. We use Harrell's concordance index to compare predictive accuracy of the models. Both PD and frailty are significantly, positively, and independently correlated with mortality: Worse PD scores and being frail are associated with a higher risk of dying. The overall PD score is a more accurate predictor of survival than frailty, although model prediction improves when both measures are included. PD and frailty independently predict mortality, suggesting that the two measures may be capturing different aspects of the same construct and that both may be important for identifying individuals at risk for adverse health outcomes. PMID- 26865401 TI - Ginsenoside Rg1 exerts a protective effect against Abeta25-35-induced toxicity in primary cultured rat cortical neurons through the NF-kappaB/NO pathway. AB - Ginsenoside Rg1 (Rg1) is a multipotent triterpene saponin extracted from ginseng, and has been proven to act as a nootropic agent against various types of neurological damage. The present study was designed to investigate the neuroprotective effect and the underlying mechanisms of Rg1 on apoptosis induced by beta-amyloid peptide 25-35 (Abeta25-35) in primary cultured cortical neurons. The primary neurons were preincubated with 20 uM Rg1 for 24 h and exposed to 10 uM Abeta25-35 for 72 h. In the present study, we found that Rg1 prevented nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) nuclear translocation and IkappaB-alpha phosphorylation in primary cultured cortical neurons after Abeta25-35 exposure by scavenging excess reactive oxygen species (ROS); ROS was measured using DCFDA and examined using a fluorescence microscope. In addition, Rg1 successfully suppressed Abeta25-35-inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in a NF-kappaB dependent manner; the suppression of NO was clearly illustrated by the NO production assay. Pretreatment of the cells with Rg1 elevated the proportion of Bcl-2/Bax, lessened the release of cytochrome c from mitochondria into cytoplasm and then blocked mitochondrial apoptotic cascades after Abeta25-35 insult by lowering NO generation. Taken together, our data demonstrate that Rg1 rescues primary cultured cortical neurons from Abeta25-35-induced cell apoptosis through the downregulation of the NF-kappaB/NO signaling pathway. PMID- 26865402 TI - The role of H2O in the electron transfer-activation of substrates using SmI2: insights from DFT. AB - The first detailed theoretical study on the synthetically important electron transfer (ET) reductant SmI2-H2O has been conducted in the context of the activation of important alkyliodide, ketone, lactone and ester substrates, processes of importance in cross-coupling. Our studies give major insights into the nature of the reagent and suggest that; (i) H2O has a high affinity for Sm(ii) and displaces iodine from the metal center; (ii) SmI2-H2O has 6-7 molecules of H2O directly bound to the metal center; (iii) binding of H2O to Sm(II) promotes coordination of the substrate to Sm(II) and subsequent ET; (iv) resultant ketyl radicals are stabilized by hydrogen-bonding to H2O. The findings add greatly to the understanding of SmI2-H2O and the role of H2O in ET processes, and will facilitate the design of new processes initiated by reductive ET. PMID- 26865403 TI - Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty. AB - RNG105 (also known as Caprin1) is a major RNA-binding protein in neuronal RNA granules, and is responsible for mRNA transport to dendrites and neuronal network formation. A recent study reported that a heterozygous mutation in the Rng105 gene was found in an autism spectrum disorder (ASD) patient, but it remains unclear whether there is a causal relation between RNG105 deficiency and ASD. Here, we subjected Rng105(+/-) mice to a comprehensive behavioral test battery, and revealed the influence of RNG105 deficiency on mouse behavior. Rng105(+/-) mice exhibited a reduced sociality in a home cage and a weak preference for social novelty. Consistently, the Rng105(+/-) mice also showed a weak preference for novel objects and novel place patterns. Furthermore, although the Rng105(+/-) mice exhibited normal memory acquisition, they tended to have relative difficulty in reversal learning in the spatial reference tasks. These findings suggest that the RNG105 heterozygous knockout leads to a reduction in sociality, response to novelty and flexibility in learning, which are implicated in ASD-like behavior. PMID- 26865404 TI - Effect of 2'-O-methyl/thiophosphonoacetate-modified antisense oligonucleotides on huntingtin expression in patient-derived cells. AB - Optimizing oligonucleotides as therapeutics will require exploring how chemistry can be used to enhance their effects inside cells. To achieve this goal it will be necessary to fully explore chemical space around the native DNA/RNA framework to define the potential of diverse chemical modifications. In this report we examine the potential of thiophosphonoacetate (thioPACE)-modified 2'-O-methyl oligoribonucleotides as inhibitors of human huntingtin (HTT) expression. Inhibition occurred, but was less than with analogous locked nucleic acid (LNA) substituted oligomers lacking the thioPACE modification. These data suggest that thioPACE oligonucleotides have the potential to control gene expression inside cells. However, advantages relative to other modifications were not demonstrated. Additional modifications are likely to be necessary to fully explore any potential advantages of thioPACE substitutions. PMID- 26865405 TI - In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6 phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA. AB - Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26 targeting vector containing a G6PC donor transgene, both delivered with adeno associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (P < 0.04). Furthermore, transgene integration has been confirmed by sequencing in the majority of the mice treated with both vectors. Targeted alleles were 4.6-fold more common in livers of mice with GSD Ia, as compared with normal littermates, at 8 months following vector administration (P < 0.02). This suggests a selective advantage for vector-transduced hepatocytes following ZFN-mediated integration of the G6Pase vector. A short-term experiment also showed that 3-month-old mice receiving the ZFN had significantly-improved biochemical correction, in comparison with mice that received the donor vector alone. These data suggest that the use of ZFNs to drive integration of G6Pase at a safe harbor locus might improve vector persistence and efficacy, and lower mortality in GSD Ia. PMID- 26865406 TI - Multiple sclerosis in families: risk factors beyond known genetic polymorphisms. AB - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by genome wide association studies and independent replication studies. A weighted genetic risk score (wGRS) was recently established using the identified MS risk loci in order to predict MS outcome including clinical and paraclinical features. Here, we present the results on a family with several affected siblings including a monozygotic triplet. The individuals were genotyped for 57 non-MHC risk loci as well as the HLA DRB1*1501 tagging SNP rs3135388 with subsequent calculation of the wGRS. Additionally, SNP array based analyses for aberrant chromosomal regions were performed for all individuals. PMID- 26865407 TI - Intranasal Pharmacokinetic Data for Triptans Such as Sumatriptan and Zolmitriptan Can Render Area Under the Curve (AUC) Predictions for the Oral Route: Strategy Development and Application. AB - Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a Cmax vs. AUC relationship was established by linear regression models for sumatriptan and zolmitriptan. The predictions of the AUC values were performed using published mean/median Cmax data and appropriate regression lines. The quotient of observed and predicted values rendered fold-difference calculation. The mean absolute error (MAE), mean positive error (MPE), mean negative error (MNE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two triptans. Also, data from the mean concentration profiles at time points of 1 hour (sumatriptan) and 3 hours (zolmitriptan) were used for the AUC prediction. The Cmax vs. AUC models displayed excellent correlation for both sumatriptan (r = .9997; P < .001) and zolmitriptan (r = .9999; P < .001). Irrespective of the two triptans, the majority of the predicted AUCs (83%-85%) were within 0.76-1.25-fold difference using the regression model. The prediction of AUC values for sumatriptan or zolmitriptan using the concentration data that reflected the Tmax occurrence were in the proximity of the reported values. In summary, the Cmax vs. AUC models exhibited strong correlations for sumatriptan and zolmitriptan. The usefulness of the prediction of the AUC values was established by a rigorous statistical approach. PMID- 26865408 TI - Erratum to: Effects of Strength Training Using Unstable Surfaces on Strength, Power and Balance Performance Across the Lifespan: A Systematic Review and Meta analysis. PMID- 26865409 TI - An update on sputum MicroRNAs in lung cancer diagnosis. AB - Lung cancer is one of the leading cause of cancer mortality in the world. It is well known that genetic damages could result in lung tumor genesis. Despite years of research, the survival rate of the patients has not been markedly improved. According to lack of high sensitivity and specificity in diagnostic tests, just about 15-20% of lung cancer cases are discovered prior to progression of the disease. In last decade, sputum biomarkers have been developed for early detection/diagnosis of lung cancer. MicroRNAs are a class of small endogenous noncoding RNAs, which act as post-transcriptional regulators. Some specific miRNAs can have multifunctions in lung development and their aberrant expression could induce lung tumor genesis. The differences in miRNAs between the normal and cancerous lung lead to emerging of a novel type of biomarkers, which can be helpful in screening of high risk individuals, diagnosis of lung cancer as well as its therapy. PMID- 26865411 TI - Environmental Presence of Mycobacterium tuberculosis Complex in Aggregation Points at the Wildlife/Livestock Interface. AB - The members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB). Infection is transmitted within and between livestock and wildlife populations, thus hampering TB control. Indirect transmission might be facilitated if MTC bacteria persist in the environment long enough to represent a risk of exposure to different species sharing the same habitat. We have, for the first time, addressed the relationship between environmental MTC persistence and the use of water resources in two TB endemic areas in southern Spain with the objective of identifying the presence of environmental MTC and its driving factors at ungulates' water aggregation points. Camera-trap monitoring and MTC diagnosis (using a new MTC complex-specific PCR technique) were carried out at watering sites. Overall, 55.8% of the water points tested positive for MTC in mud samples on the shore, while 8.9% of them were positive in the case of water samples. A higher percentage of MTC-positive samples was found at those waterholes where cachectic animals were identified using camera-trap monitoring, and at the smallest waterholes. Our results help to understand the role of indirect routes of cross-species TB transmission and highlight the importance of certain environmental features in maintaining infection in multihost systems. This will help to better target actions and implement control strategies for TB at the wildlife/livestock interface. PMID- 26865412 TI - Immunomodulatory drugs inhibit TLR4-induced type-1 interferon production independently of Cereblon via suppression of the TRIF/IRF3 pathway. AB - Thalidomide and its derivatives, collectively referred to as immunomodulatory drugs (IMiDs), are effective inhibitors of inflammation and are known to inhibit TLR-induced TNFalpha production. The identification of Cereblon as the receptor for these compounds has led to a rapid advancement in our understanding of IMiD properties; however, there remain no studies addressing the role of Cereblon in mediating the suppressive effect of IMiDs on TLR responses. Here, we developed Cereblon-deficient mice using the CRISPR-Cas9 system. TLR-induced cytokine responses were unaffected by Cereblon deficiency in vivo Moreover, IMiD treatment inhibited cytokine production even in the absence of Cereblon. The IMiD-induced suppression of cytokine production therefore occurs independently of Cereblon in mice. Further investigation revealed that IMiDs are potent inhibitors of TLR induced type-1 interferon production via suppression of the TRIF/IRF3 pathway. These data suggest that IMiDs may prove effective in the treatment of disorders characterized by the ectopic production of type-1 interferon. Significantly, these properties are mediated separately from thalidomide's teratogenic receptor, Cereblon. Thus, certain therapeutic properties of Thalidomide can be separated from its harmful side effects. PMID- 26865413 TI - Detecting and modelling delayed density-dependence in abundance time series of a small mammal (Didelphis aurita). AB - We study the population size time series of a Neotropical small mammal with the intent of detecting and modelling population regulation processes generated by density-dependent factors and their possible delayed effects. The application of analysis tools based on principles of statistical generality are nowadays a common practice for describing these phenomena, but, in general, they are more capable of generating clear diagnosis rather than granting valuable modelling. For this reason, in our approach, we detect the principal temporal structures on the bases of different correlation measures, and from these results we build an ad-hoc minimalist autoregressive model that incorporates the main drivers of the dynamics. Surprisingly our model is capable of reproducing very well the time patterns of the empirical series and, for the first time, clearly outlines the importance of the time of attaining sexual maturity as a central temporal scale for the dynamics of this species. In fact, an important advantage of this analysis scheme is that all the model parameters are directly biologically interpretable and potentially measurable, allowing a consistency check between model outputs and independent measurements. PMID- 26865414 TI - Prion infection impairs lysosomal degradation capacity by interfering with rab7 membrane attachment in neuronal cells. AB - Prions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly beta-sheeted aggregated isoform (PrP(Sc)) of the cellular prion protein (PrP(c)). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrP(c) into PrP(Sc). Within neurons, PrP(Sc) accumulates at the plasma membrane and in vesicles of the endocytic pathway. To better understand the mechanisms underlying neuronal dysfunction and death it is critical to know the impact of PrP(Sc) accumulation on cellular pathways. We have investigated the effects of prion infection on endo-lysosomal transport. Our study demonstrates that prion infection interferes with rab7 membrane association. Consequently, lysosomal maturation and degradation are impaired. Our findings indicate a mechanism induced by prion infection that supports stable prion replication. We suggest modulation of endo-lysosomal vesicle trafficking and enhancement of lysosomal maturation as novel targets for the treatment of prion diseases. PMID- 26865415 TI - Pharmacodynamic Actions of a Long-Acting PTH Analog (LA-PTH) in Thyroparathyroidectomized (TPTX) Rats and Normal Monkeys. AB - Hypoparathyroidism is a disease of chronic hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone (PTH). PTH and analogs of the hormone are of interest as potential therapies. Accordingly, we examined the pharmacological properties of a long-acting PTH analog, [Ala(1,3,12,18,22) , Gln(10) ,Arg(11) ,Trp(14) ,Lys(26) ]-PTH(1-14)/PTHrP(15-36) (LA-PTH) in thyroparathyroidectomized (TPTX) rats, a model of HP, as well as in normal monkeys. In TPTX rats, a single intravenous administration of LA-PTH at a dose of 0.9 nmol/kg increased serum calcium (sCa) and decreased serum phosphate (sPi) to near-normal levels for longer than 48 hours, whereas PTH(1-34) and PTH(1-84), each injected at a dose 80 fold higher than that used for LA-PTH, increased sCa and decreased sPi only modestly and transiently (<6 hours). LA-PTH also exhibited enhanced and prolonged efficacy versus PTH(1-34) and PTH(1-84) for elevating sCa when administered subcutaneously (s.c.) into monkeys. Daily s.c. administration of LA-PTH (1.8 nmol/kg) into TPTX rats for 28 days elevated sCa to near normal levels without causing hypercalciuria or increasing bone resorption markers, a desirable goal in the treatment of hypoparathyroidism. The results are supportive of further study of long-acting PTH analogs as potential therapies for patients with hypoparathyroidism. (c) 2016 American Society for Bone and Mineral Research. PMID- 26865416 TI - Climbing With a Head-Mounted Display: Dual-Task Costs. AB - OBJECTIVE: We explored the dual-task costs of climbers performing a visual communication task using a head-mounted display (HMD) while simultaneously climbing along a vertical surface. BACKGROUND: Climbing is affected by secondary auditory cognitive tasks, and climbing impairs later recall of secondary task information; the effects of visually presented tasks are less clear. Given that HMDs are projected to be adopted into emergency response work, questions are raised about the effects of HMD use during climbing or other physical tasks. METHOD: Climbers performed five conditions-a climbing-only condition, two dual task climbing conditions (words presented on the HMD with and without auditory warnings while climbing), and two seated control conditions (words presented on the HMD with and without auditory warnings)-in a repeated-measures design. Motion data were also collected to examine participant motion around word presentation. RESULTS: We found a decrease in both climbing performance and word recall under dual-task conditions, paralleling results found in previous research using auditory tasks. Participants slowed around word presentations on the HMD. Additional comparisons to previous research indicate that physical tasks may be more detrimental to word recall than are seated tasks and that visual stimuli might hinder climbing performance more than do audible stimuli. CONCLUSION: Complex physical activity, like climbing, is disruptive to memory rehearsal and later recall, and cognitive tasks disrupt physical performance. APPLICATION: Avoiding cognitive HMD tasks requiring later recall during complex physical activity is advisable. However, these systems may be developed to provide intelligent assistance, or memory augmentation, in these settings. PMID- 26865418 TI - Limited long-term outcome of single-session soft palate interstitial radiofrequency surgery for habitual snoring in tertiary care academic referral centre: Our experience on 77 patients. PMID- 26865417 TI - Protective efficacy of the chimeric Staphylococcus aureus vaccine candidate IC in sepsis and pneumonia models. AB - Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151 277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17 skewed cellular immune responses based on cytokine profiles and CD4(+) T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-gamma) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia. PMID- 26865420 TI - Magnetic resonance imaging reveals the complementary effects of decongestant and Breathe Right Nasal Strips on internal nasal anatomy. AB - OBJECTIVES/HYPOTHESIS: This magnetic resonance imaging (MRI) study of 26 subjects with nasal congestion was performed to assess in the complete nasal passage both the anatomical effect of the marketed Breathe Right Nasal Strip (BRNS) relative to placebo and the potential adjunctive effect of using a decongestant in combination with the BRNS. STUDY DESIGN: Randomized, crossover study. METHODS: The study consisted of two parts, the first involving application of either the BRNS or the placebo strip in a randomized, crossover design with evaluator blinding, and repeated MRI scanning; and the second a sequential process of decongestant administration, MRI scanning, application of the BRNS, and repeated MRI. The same anatomical MRI protocol was used throughout. Nasal patency was assessed in the whole nasal passage and eight subregions (by inferior-superior, anterior-posterior division). Numerical response scores representing subjective nasal congestion were also obtained. RESULTS: Results demonstrate significant anatomical enlargement with the BRNS relative to placebo (P < .001), as well as an additive effect of using a decongestant in combination with the BRNS; both supported by a strong and significant negative correlation with the subjective nasal response measures of nasal congestion (r = -0.98, P = .002). Furthermore, analysis of the nasal subregions indicates that this adjunctive effect arises from a partially localized action of the complementary products: the BRNS acting primarily anteriorly in the nose and the decongestant mainly posteriorly. CONCLUSIONS: The BRNS alone significantly increases nasal patency and alleviates perceived nasal congestion, and additional relief of symptoms can be obtained with simultaneous use of a decongestant. LEVEL OF EVIDENCE: 1b. Laryngoscope, 126:2205-2211, 2016. PMID- 26865419 TI - Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma. AB - Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor beta (PDGFR-beta) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-beta, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor promoting effect of CAFs/MSCs. KM12SM human colon cancer cells alone or KM12SM cells with MSCs were transplanted into the cecal wall of nude mice. Co implantation of KM12SM cells with MSCs into the cecal wall of nude mice produced tumors with abundant stromal component and promoted tumor growth and lymph node metastasis. Single treatment with regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction. This tumor inhibitory effect of regorafenib was more obvious in tumors developed by co implanting KM12SM cells with MSCs. Our data suggested that targeting of the tumor microenvironment with regorafenib affected tumor cell-MSC interaction, which in turn inhibited the growth and metastasis of colon cancer. PMID- 26865421 TI - Birth Outcomes, Intervention Frequency, and the Disappearing Midwife-Potential Hazards of Central Fetal Monitoring: A Single Center Review. AB - INTRODUCTION: Many birth units use central fetal monitoring (CFM) under the assumption that greater surveillance improves perinatal outcomes. The unexpected loss of the CFM system at a tertiary unit provided a unique opportunity to evaluate outcomes and staff attitudes toward CFM. METHODS: This retrospective cohort study compared patient data from 2,855 electronically monitored women delivering over a 12-month period, where CFM was available for the first 6 months but unavailable for the following 6 months. Primary outcomes relating to neonatal morbidity and secondary outcomes relating to intrapartum interventions were examined. Additionally, birth unit staff members were surveyed about aspects of care related to CFM. RESULTS: There were no significant differences in perinatal outcomes between the cohorts. While unadjusted analysis suggested a lower spontaneous vaginal birth rate (55.4% vs 60.3%) and a higher cesarean delivery rate (25.1% vs 22.0%, p = 0.026), together with higher epidural (53.0% vs 49.2%, p = 0.04) and fetal blood sampling (11.8% vs 9.4%, p = 0.03) rates in the presence of CFM, these differences were lost when adjusted for prostaglandin ripening. Over half of the staff (56.0% of midwives, 54.0% of obstetricians) reported spending more time with the laboring woman in the period without CFM. CONCLUSIONS: This single institution's experience indicates that in birth units staffed for one-to-one care in labor, central fetal monitoring does not appear to be associated with either a benefit on perinatal outcomes or an increase in cesarean delivery and other interventions. However, it is associated with a reduction in the time a midwife spends with the laboring woman. PMID- 26865422 TI - Studies of Hematopoietic Cell Differentiation with a Ratiometric and Reversible Sensor of Mitochondrial Reactive Oxygen Species. AB - AIMS: Chronic elevations in cellular redox state are known to result in the onset of various pathological conditions, but transient increases in reactive oxygen species (ROS)/reactive nitrogen species (RNS) are necessary for signal transduction and various physiological functions. There is a distinct lack of reversible fluorescent tools that can aid in studying and unraveling the roles of ROS/RNS in physiology and pathology by monitoring the variations in cellular ROS levels over time. In this work, we report the development of ratiometric fluorescent sensors that reversibly respond to changes in mitochondrial redox state. RESULTS: Photophysical studies of the developed flavin-rhodamine redox sensors, flavin-rhodamine redox sensor 1 (FRR1) and flavin-rhodamine redox sensor 2 (FRR2), confirmed the reversible response of the probes upon reduction and re oxidation over more than five cycles. The ratiometric output of FRR1 and FRR2 remained unaltered in the presence of other possible cellular interferants (metals and pH). Microscopy studies indicated clear mitochondrial localization of both probes, and FRR2 was shown to report the time-dependent increase of mitochondrial ROS levels after lipopolysaccharide stimulation in macrophages. Moreover, it was used to study the variations in mitochondrial redox state in mouse hematopoietic cells at different stages of embryonic development and maturation. INNOVATION: This study provides the first ratiometric and reversible probes for ROS, targeted to the mitochondria, which reveal variations in mitochondrial ROS levels at different stages of embryonic and adult blood cell production. CONCLUSIONS: Our results suggest that with their ratiometric and reversible outputs, FRR1 and FRR2 are valuable tools for the future study of oxidative stress and its implications in physiology and pathology. Antioxid. Redox Signal. 24, 667-679. PMID- 26865423 TI - Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later. AB - Depression is linked to increased amygdala activation to neutral and negatively valenced facial expressions. Amygdala activation may be predictive of changes in depressive symptoms over time. However, most studies in this area have focused on small, predominantly female and homogenous clinical samples. Studies are needed to examine how amygdala reactivity relates to the course of depressive symptoms dimensionally, prospectively and in populations diverse in gender, race and socioeconomic status. A total of 156 men from predominately low-income backgrounds completed an fMRI task where they viewed emotional facial expressions. Left and right amygdala reactivity to neutral, but not angry or fearful, facial expressions relative to a non-face baseline at age 20 predicted greater depressive symptoms 2 years later, controlling for age 20 depressive symptoms. Heightened bilateral amygdala reactivity to neutral facial expressions predicted increases in depressive symptoms 2 years later in a large community sample. Neutral facial expressions are affectively ambiguous and a tendency to interpret these stimuli negatively may reflect to cognitive biases that lead to increases in depressive symptoms over time. Individual differences in amygdala reactivity to neutral facial expressions appear to identify those at most risk for a more problematic course of depressive symptoms across time. PMID- 26865424 TI - Neural correlates of prosocial peer influence on public goods game donations during adolescence. AB - A unique feature of adolescent social re-orientation is heightened sensitivity to peer influence when taking risks. However, positive peer influence effects are not yet well understood. The present fMRI study tested a novel hypothesis, by examining neural correlates of prosocial peer influence on donation decisions in adolescence. Participants (age 12-16 years; N = 61) made decisions in anonymous groups about the allocation of tokens between themselves and the group in a public goods game. Two spectator groups of same-age peers-in fact youth actors were allegedly online during some of the decisions. The task had a within subjects design with three conditions: (1) EVALUATION: spectators evaluated decisions with likes for large donations to the group, (2) Spectator: spectators were present but no evaluative feedback was displayed and (3) Alone: no spectators nor feedback. Results showed that prosocial behavior increased in the presence of peers, and even more when participants received evaluative feedback from peers. Peer presence resulted in enhanced activity in several social brain regions including medial prefrontal cortex, temporal parietal junction (TPJ), precuneus and superior temporal sulcus. TPJ activity correlated with donations, which suggests similar networks for prosocial behavior and sensitivity to peers. These findings highlight the importance of peers in fostering prosocial development throughout adolescence. PMID- 26865426 TI - A novel C8orf37 splice mutation and genotype-phenotype correlation for cone-rod dystrophy. AB - BACKGROUND: To identify the disease-causing mutation in a consanguineous family of Morrocan origin with syndromic autosomal recessive (ar) cone-rod dystrophy (CRD) in two patients and describe genotype-phenotype correlations. MATERIALS AND METHODS: Genome-wide homozygosity mapping and direct sequencing of C8orf37, located in a homozygous interval, was performed in the family. mRNA analysis revealed the effect of the newly identified splice-site mutation. For a comparative analysis phenotypic and genetic data of C8orf37 mutations were extracted from published cases. RESULTS: The new splice-site mutation c.155+2T>C identified in the family results in a skipping of 82 bp. The CRD phenotypes of our patients were consistent with previous reports. Non-ocular findings in our patients and two previously described patients were postaxial polydactyly present at birth. Both families with additional postaxial polydactyly had splice site mutations affecting intron 1 of C8orf37, one at the slice donor and one at the splice acceptor site. CONCLUSIONS: This report extends the genotypic spectrum of C8orf37-associated retinal dystrophies and demonstrates for the first time a genotype-phenotype correlation between an arCRD-polydactyly-association and truncating germline mutations affecting the N-terminal region of the protein. Furthermore, our findings underline the ciliary function of C8orf37 protein. PMID- 26865425 TI - Anxiety and social deficits have distinct relationships with amygdala function in autism spectrum disorder. AB - Current neural models of autism spectrum disorder (ASD) and anxiety disorders suggest hyperactivation of amygdala in anxiety, but hypoactivation of amygdala in ASD. The objectives of this study were to (i) test the hypothesis that amygdala activity measured by functional magnetic resonance imaging (fMRI) represents a hybrid signal of opposing social functions and anxiety symptoms, and (ii) determine whether longstanding findings of decreased amygdala activation in ASD apply only to those individuals with ASD and low levels of anxiety. During fMRI scanning, 81 youth with ASD and 67 non-ASD control participants completed a face recognition paradigm that elicits robust amygdala activation. Only individuals with ASD and low anxiety levels (a subsample of 28 participants) showed decreased amygdala activation relative to controls. In the ASD group, anxiety symptoms were positively correlated with amygdala activity across the full ASD group, whereas core ASD symptoms (including social deficits) were negatively correlated. Results indicate that hypoactivation of amygdala in ASD, a suggestive finding first reported nearly 20 years ago, can be masked by comorbid anxiety-thus bringing enhanced clarity to this line of work. Amygdala activity represents a hybrid signal of emotion and social processes that cannot be reduced to either alone. PMID- 26865429 TI - Risky sexual behaviors among sexually active first-year students matriculating at a historically Black college: Is a positive self-image an instigator? AB - A sample of 498 sexually active first-year students matriculating at a historically Black college in North Carolina was used to determine correlates of risky sexual behaviors. In an Ordinary Least Squares regression, the self-esteem element "I take a positive attitude toward myself" (B = 1.12, p = .05), non condom use because of partner issues (B = .53, p = .05) and being drunk or high (B = 1.20, p = .001), oral sex (B = 1.74, p = .001), anal sex (B = .61, p = .04), and bisexuality (B = .85, p = .03) all increased the number of these behaviors. Higher scores on the condom usage scale (B = -.38, p = .002) were found to decrease the number of risky sexual behaviors. Illicit drug use was an underpinning of the surprisingly positive relationship between positive self image and risky sexual behaviors. It was concluded that school-based social workers, mental health care professionals, and community-based prevention providers can play a critical role in the training of peer facilitators, development, and supervision of peer-driven risk-reduction programs to address the complex interplay among self-esteem, sex, and substances. PMID- 26865430 TI - Effect of Adopters' Lifestyles and Animal-Care Knowledge on Their Expectations Prior to Companion-Animal Guardianship. AB - Human expectations can greatly affect the human-companion animal relationship, sometimes putting nonhuman animals at risk for relinquishment. At 20 animal shelters in Southern Ontario, Canada, potential adopters (N = 234) completed a questionnaire regarding their lifestyle, companion animal-care knowledge, and preadoption expectations of their adopted companion animals. Linear mixed models were used to assess the associations of adopters' lifestyles and companion animal care knowledge with their expectations for animal behavior, the human-companion animal relationship, and the effort required in companion-animal guardianship. Dog adopters had higher expectations than cat adopters for their companion animal's behavior (p < .001), the human-companion animal relationship (p < .001), and the effort required in companion-animal guardianship (p < .001). Adopters' human relationship statuses were also associated with expectations for the human companion animal relationship (p = .002). As adopters' companion animal-care knowledge increased, so did their expectations for the effort required in companion-animal guardianship (p < .001). An understanding of adopters' expectations prior to adoption will help animal shelters better match, educate, and prepare adopters for their lives with companion animals. PMID- 26865431 TI - Seasonal forecasting of lightning and thunderstorm activity in tropical and temperate regions of the world. AB - Thunderstorms are convective systems characterised by the occurrence of lightning. Lightning and thunderstorm activity has been increasingly studied in recent years in relation to the El Nino/Southern Oscillation (ENSO) and various other large-scale modes of atmospheric and oceanic variability. Large-scale modes of variability can sometimes be predictable several months in advance, suggesting potential for seasonal forecasting of lightning and thunderstorm activity in various regions throughout the world. To investigate this possibility, seasonal lightning activity in the world's tropical and temperate regions is examined here in relation to numerous different large-scale modes of variability. Of the seven modes of variability examined, ENSO has the strongest relationship with lightning activity during each individual season, with relatively little relationship for the other modes of variability. A measure of ENSO variability (the NINO3.4 index) is significantly correlated to local lightning activity at 53% of locations for one or more seasons throughout the year. Variations in atmospheric parameters commonly associated with thunderstorm activity are found to provide a plausible physical explanation for the variations in lightning activity associated with ENSO. It is demonstrated that there is potential for accurately predicting lightning and thunderstorm activity several months in advance in various regions throughout the world. PMID- 26865433 TI - User perception on various designs of tongue scrapers: an observational survey. AB - AIM: The aim of this study was to identify the participants' preference and perception of effectiveness with respect to nine commercially available tongue scrapers. As secondary aim, perception of discomfort and suspected sharpness were assessed. In addition, the first impression of the design of the various tongue scrapers was evaluated. MATERIALS AND METHODS: This was an observational survey without blinding to the products. At first impression, participants were given nine tongue scrapers and were asked to immediately use all, and to point out which of the scrapers they preferred most. Subsequently, a 14-day familiarization period followed. At the follow-up appointment, all participants received a questionnaire which used a visual analogue scale (VAS) to evaluate their perception of the various scrapers used. Questions regarding the perceived efficacy, discomfort and pain were posed. Data were analysed statistically by anova. T-tests were used for 'post hoc' analysis and Bonferroni corrections were used for multiple comparisons. RESULTS: In total, 50 participants completed the assessment. The primary parameter 'efficacy' showed scores that ranged from 4.09 to 6.43 (P < 0.001) for the nine tongue scrapers. The secondary parameters 'sharpness' (range from 3.31 to 6.26) and 'discomfort' (range from 5.67 to 8.33) showed significant differences as well (P < 0.001). A significant negative correlation (R = -0.850; P = 0.004) between the perceived sharpness and discomfort was observed. CONCLUSION: The perception of effectiveness varied among the various tongue-cleaning device designs. No single feature stood out as being specifically related to perception of effectiveness. Sharpness and comfort were negatively correlated. Comfort and effectiveness were positively correlated. The results from this study indicated that participants found TS6 and TS8 to be the most comfortable and the most effective. However, TS8 scored higher for inducing a higher gag reflex. PMID- 26865432 TI - Integration of lipidomics and transcriptomics unravels aberrant lipid metabolism and defines cholesteryl oleate as potential biomarker of prostate cancer. AB - In-depth delineation of lipid metabolism in prostate cancer (PCa) is significant to open new insights into prostate tumorigenesis and progression, and provide potential biomarkers with greater accuracy for improved diagnosis. Here, we performed lipidomics and transcriptomics in paired prostate cancer tumor (PCT) and adjacent nontumor (ANT) tissues, followed by external validation of biomarker candidates. We identified major dysregulated pathways involving lipogenesis, lipid uptake and phospholipids remodeling, correlated with widespread lipid accumulation and lipid compositional reprogramming in PCa. Specifically, cholesteryl esters (CEs) were most prominently accumulated in PCa, and significantly associated with cancer progression and metastasis. We showed that overexpressed scavenger receptor class B type I (SR-BI) may contribute to CEs accumulation. In discovery set, CEs robustly differentiated PCa from nontumor (area under curve (AUC) of receiver operating characteristics (ROC), 0.90-0.94). In validation set, CEs potently distinguished PCa and non-malignance (AUC, 0.84 0.91), and discriminated PCa and benign prostatic hyperplasia (BPH) (AUC, 0.90 0.96), superior to serum prostate-specific antigen (PSA) (AUC = 0.83). Cholesteryl oleate showed highest AUCs in distinguishing PCa from non-malignance or BPH (AUC = 0.91 and 0.96). Collectively, our results unravel the major lipid metabolic aberrations in PCa and imply the potential role of CEs, particularly, cholesteryl oleate, as molecular biomarker for PCa detection. PMID- 26865434 TI - Infrared videoangiographic assessment of cochlear nerve vasculature during middle fossa surgery. PMID- 26865435 TI - The adenomatoid odontogenic tumour: an update of selected issues. AB - The aim of this update was to present the recent notable progress within remaining questions relating to the adenomatoid odontogenic tumour (AOT). Selected issues that were studied included the following: (i) AOT history and terminology, (ii) the so-called peripheral AOT, (iii) AOT and the gubernaculum dentis and (iv) the so-called adenomatoid odontogenic cyst (AOC). The earliest irrefutable European case of AOT was described in 1915 by Harbitz as 'cystic adamantoma'. Recently, Ide et al. have traced two Japanese cases with irrefutable proof described by Nakayama in 1903. The so-called peripheral (gingival) variant of AOT seems to cover a dual pathogenesis, both an 'erupted intraosseous' and an 'extraosseous' (gingival) one. In 1992, we theorized that the generally unnoticed gubernaculum dentis (cord and canal) seems to be involved in the development of AOT. Ide et al. have concluded that the dental lamina in the gubernacular cord seems to be an embryonic source of the vast majority of AOTs. The suggestion by Marx and Stern to change the nomenclature of AOT to adenomatoid odontogenic cyst (AOC) is critically discussed. The present authors agree on the background of the work of several groups of researchers and WHO/IARC classifications that the biology of the follicular variant of AOT is already fully explained and does not make room for any change in diagnostic terms. Further, there is no reason to change terminology in this case where improvements or conditions to better clinical management are not an issue. PMID- 26865436 TI - Cherry picking into the digital age! PMID- 26865437 TI - In bifurcation PCI, as in everyday life, the consequences of kissing may not always be the same. PMID- 26865438 TI - Expanding options for retrograde recanalisation of right coronary artery chronic total occlusions. PMID- 26865439 TI - Prolonged dual antiplatelet therapy: a potential mitigator of the adverse effects of local haemodynamic shear stress in high-risk coronary regions? PMID- 26865440 TI - Novel retrograde approach for percutaneous treatment of chronic total occlusions of the right coronary artery using ipsilateral collateral connections: a European centre experience. AB - AIMS: A systematic description of the percutaneous treatment of chronic total occlusions (CTOs) of the right coronary artery (RCA) using ipsilateral collateral connections (CCs) for the retrograde approach has never been carried out. Our aim was to investigate this issue systematically. METHODS AND RESULTS: Based on the experiences of a European high-volume CTO centre: 1) a generalised scheme of the varying anatomic courses of ipsilateral CCs bridging CTOs of the RCA was developed; 2) important stepwise technical advice for the ipsilateral retrograde approach was formulated; and 3) a supportive clinical case series was assessed. Of a total of 158 patients with CTOs of the RCA, 30% (n=47) revealed ipsilateral CCs of the RCA. Five different types (A-E) of ipsilateral CCs were assessed. The retrograde ipsilateral approach was attempted in nine patients, and was completed successfully in 89% (8/9 patients). Median left ventricular ejection fraction was 56% (interquartile range [IQR]: 50-60%) and mean J-CTO score was 2.9 (standard error of mean [SEM]: +/-0.3). Median procedural duration time was 150 min (IQR 117-160 min), with a median applied amount of contrast of 360 ml (IQR 270-400 ml). No relevant complications, such as acute renal failure or severe bleedings, occurred. CONCLUSIONS: The percutaneous treatment of CTOs of the RCA using ipsilateral CCs for the retrograde approach might provide a novel treatment alternative for patients with CTOs of the RCA in specific clinical situations. PMID- 26865442 TI - Prediction of the true fractional flow reserve of left main coronary artery stenosis with concomitant downstream stenoses: in vitro and in vivo experiments. AB - AIMS: The functional impact of downstream coronary stenoses on left main coronary artery (LMCA) stenosis has not been fully elucidated. This study therefore aimed to use in vitro and in vivo experiments to assess two novel equations that predict the true fractional flow reserve (FFR) of a left main coronary artery (LMCA) stenosis with concomitant downstream stenoses. METHODS AND RESULTS: Two novel equations were derived. One equation predicts the true fractional flow reserve (FFR) of an LMCA stenosis with a downstream stenosis (Equation A), and the other predicts the true FFR of an LMCA stenosis with downstream stenoses in both the left anterior descending and left circumflex arteries (Equation B). The equations were validated in both in vitro and in vivo models of the coronary circulation. The agreements between the apparent FFR (FFRapp), the predicted FFR (FFRpred) and the true FFR (FFRtrue) were assessed by Passing-Bablok regression analysis. Passing-Bablok regression analysis revealed that there were fixed proportional errors between FFRapp-m and FFRtrue-m, though a very small fixed error and no proportional errors between FFRpred-m and FFRtrue-m. The absolute differences between FFRpred and FFRtrue were significantly lower as compared to those between FFRapp and FFRtrue in all experiments. CONCLUSIONS: Two novel equations which predict the true FFR of LMCA stenosis were demonstrated to be correct. The study also revealed that the functional impact of downstream stenoses on the LMCA stenosis became stronger when the downstream stenoses became more severe. PMID- 26865441 TI - Efficacy of kissing balloon inflation after provisional stenting in bifurcation lesions guided by intravascular ultrasound: short and midterm results of the J REVERSE registry. AB - AIMS: Our aim was to investigate the efficacy of the kissing balloon technique (KBT) in the provisional stenting of bifurcation lesions guided by intravascular ultrasound. METHODS AND RESULTS: In the J-REVERSE registry, 300 non-left main bifurcation lesions in 299 patients were divided into two groups, KBT (n=163) and non-KBT (n=137). Patient and lesion characteristics were similar except for a higher prevalence of diabetic patients in the non-KBT group. The major adverse cardiac events (MACE) incidence at nine-month follow-up, including target lesion revascularisation, myocardial infarction, stent thrombosis, and death, was 6.3% in the KBT group versus 9.1% in the non-KBT group (p=0.47). Regardless of more SB dissection (10.5% vs. 1.5%, p=0.001), the KBT group obtained a greater luminal volume in the proximal main vessel (MV) (7.8+/-2.3 vs. 7.0+/-2.0 mm3/mm, p=0.006), maintained larger minimal lumen diameter at follow-up (2.73+/-0.43 vs. 2.63+/-0.39 mm, p=0.04), and demonstrated less binary side branch (SB) restenosis (9.7% vs. 21.0%, p=0.0004), which was beneficial for both true and non-true bifurcation lesions. Multivariate analysis showed the efficacy of KBT on SB restenosis (OR 0.28, 95% CI: 0.12-0.62, p=0.002). CONCLUSIONS: Although the KBT increased SB dissection, it provided greater luminal gain in the proximal MV and SB with a similar MACE rate to non-KBT treatment up to nine-month follow-up. PMID- 26865443 TI - Long-term outcome of FFR-guided PCI for stable coronary artery disease in daily clinical practice: a propensity score-matched landmark analysis. AB - AIMS: Our aim was to investigate the strength of fractional flow reserve (FFR) guided percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) in daily practice. METHODS AND RESULTS: For this study, 3,512 patients with stable CAD and at least one 50-89% coronary stenosis were identified; those patients thought to require PCI (n=1,716) were selected. Of these, 962 (56%) were treated based on angiography (XA) alone, whereas 754 patients (44%) had an FFR-guided treatment. In the latter group, 321 patients (43%) were reallocated to another treatment, predominantly medical treatment. After propensity score matching, the number of indicated lesions was 957 in the XA-guided group and 947 in the FFR-guided group. FFR guidance resulted in PCI deferral in 462 lesions (48.8%). In a seven-day landmark analysis, the rate of periprocedural myocardial infarction (MI) was less than half in the FFR-guided group (p>0.05). For the eight-day to four-year follow-up period, FFR guidance resulted in a significantly lower rate of the combined endpoint of death/MI (hazard ratio [HR] 0.63) and MI-driven target lesion revascularisation (HR 0.35). CONCLUSIONS: This large, retrospective study shows that performing FFR has a significant impact on therapeutic strategy and demonstrates the favourable long term outcome of FFR-guided PCI in an "all-comers" population of patients with stable CAD in daily clinical practice. PMID- 26865444 TI - STENTYS Self-Apposing sirolimus-eluting stent in ST-segment elevation myocardial infarction: results from the randomised APPOSITION IV trial. AB - AIMS: We sought to investigate the impact of the self-apposing, sirolimus-eluting STENTYS stent on midterm and long-term stent apposition and strut coverage compared with a zotarolimus-eluting balloon-expandable stent in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS: In the APPOSITION IV trial, 152 STEMI patients were randomised (3:2) to the self-apposing, sirolimus-eluting STENTYS stent or a commercially available zotarolimus-eluting balloon-expandable stent at 12 sites in five countries with angiographic follow-up and optical coherence tomography at four or nine months. At four months, a lower percentage of malapposed stent struts was observed in the STENTYS group (N=21; Nstruts=501) compared with controls (N=26; Nstruts=326; 0.07% vs. 1.16%; p=0.002) with significantly more covered struts, using a 20 um cut-off (94.32% vs. 89.09%; p=0.003). At nine months, the primary endpoint (percentage malapposed stent struts) was similar in both groups (STENTYS, N=40; Nstruts=566; control, N=21; Nstruts=292), showing complete apposition (p=0.55) and near total (>96%) coverage (p=0.58). CONCLUSIONS: In STEMI patients undergoing PPCI, the self-apposing, sirolimus-eluting STENTYS stent was equivalent to a conventional drug-eluting balloon-expandable stent with respect to late stent strut apposition and coverage at nine months. However, stent strut apposition and coverage at four months were significantly better in the STENTYS group. PMID- 26865445 TI - Impact of bivalirudin on post-procedural epicardial blood flow, risk of stent thrombosis and mortality after percutaneous coronary intervention. AB - AIMS: We aimed to assess the association of bivalirudin with post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow, acute (<=24 hours) and 30-day stent thrombosis (ST), and one-year mortality. METHODS AND RESULTS: The study included 11,623 patients undergoing percutaneous coronary intervention (PCI). The primary outcomes were post-procedural TIMI flow grade <=2 and definite acute ST. In groups treated with bivalirudin (n=3,135), abciximab plus unfractionated heparin (UFH; n=3,539) and UFH alone (n=4,949), post-procedural TIMI was <=2 in 5.2%, 3.2% and 3.2% of patients, respectively (adjusted odds ratio [OR]=1.96 [95% confidence interval] 1.47-2.56 for bivalirudin versus abciximab plus UFH and OR=1.56 [1.20-2.04] for bivalirudin versus UFH). Definite acute ST occurred in two patients (0.06%) treated with bivalirudin, two patients (0.06%) treated with abciximab plus UFH, and seven patients (0.14%) treated with UFH (p=0.47). Bivalirudin was not associated with increased risk of 30-day ST (hazard ratio [HR]=1.20 [0.59-2.43] versus abciximab plus UHF, and HR=0.93 [0.48-1.82] versus UFH) or one-year mortality (HR=0.95 [0.70-1.28] versus abciximab plus UHF, and HR=1.05 [0.78-1.41] versus UFH). CONCLUSIONS: Bivalirudin was associated with higher risk of suboptimal post-PCI TIMI flow but not with increased risk of acute or 30-day definite ST or one-year mortality compared with abciximab plus UFH or UFH alone. PMID- 26865446 TI - Patency of coronary side branches covered by an everolimus-eluting bioresorbable vascular scaffold: clinical outcomes and computed tomography scan follow-up. AB - AIMS: The behaviour of side branches (SBs) covered by a bioresorbable vascular scaffold (BVS) is not well known. This study analysed the rate of side branch occlusion (SBO) immediately after BVS implantation, its clinical impact, predictors of SBO and the fate of such SBs at follow-up. METHODS AND RESULTS: We assessed 140 patients with 346 jeopardised SBs divided into three groups: small (<1 mm, n=181), intermediate (1-2 mm, n=102) and large (>2 mm, n=63). SBO was defined as a TIMI flow 0 or 1. Computed tomography was scheduled at six months for patients with jailed SBs >1 mm. Immediate occlusion occurred in 31 (9%) SBs: 22 (12%) small, 8 (8%) intermediate and one (1.6%) large, while post-procedural SBO was 5.5%. In-hospital events included one thrombosis (0.7%) and eight non-Q wave myocardial infarctions (6%). After 17+/-3 months, one patient died (0.7%) and six patients needed repeat revascularisation (4%). Re-evaluation showed no late SBO at 7+/-3 months. Predictors of SBO were: small SBs (OR 2.06, 95% CI: 1.08-4.63; p<0.05) and stenosis >50% at the origin (OR 17.22, 95% CI: 7.79-38.10; p<0.01). CONCLUSIONS: The incidence of SBO and its clinical impact were low when SBs >1 mm were covered. These favourable results were maintained at midterm. PMID- 26865447 TI - In vitro evaluation of valve-in-valve combinations using a SAPIEN XT valve implanted within PERIMOUNT and Magna Ease pericardial bioprostheses. AB - AIMS: Implantation of a transcatheter heart valve to treat valve failure is an attractive option which is being used more frequently. Despite large clinical experience there is a paucity of in vitro data to support this treatment. Our aim was to provide in vitro performance data on the SAPIEN XT transcatheter heart valve implanted within two types of pericardial surgical heart valve. METHODS AND RESULTS: A SAPIEN XT was implanted within multiple sizes, i.e., 21, 23, 25 of Magna Ease and explanted calcified PERIMOUNT valves. Each combination underwent in vitro testing according to the ISO 5840 guidance. Combinations were evaluated for embolisation and acute and long-term haemodynamic performance. All combinations met the ISO 5840 minimum requirements for effective orifice area (EOA) and regurgitant fraction at the initiation of the study, after 20 million and 200 million cycles. EOA was above 1.4 cm2 for all valve combinations with Magna Ease and above 1.22 cm2 with PERIMOUNT combinations. Regurgitant fraction was <=7% for SAPIEN XT-Magna Ease combinations and was <=10% for SAPIEN XT PERIMOUNT combinations, which also met the ISO requirements. No embolisation was observed. The largest migration was 1.2 mm. CONCLUSIONS: In vitro tests demonstrate excellent haemodynamic performance and durability in the six VIV combinations which are commonly seen in clinical practice. PMID- 26865448 TI - A creative transcatheter approach to correct complex recurring mitral regurgitation after previous surgical repair. AB - AIMS: Leaflet perforations are usually not treated by interventional therapy. In our case we describe a clinical scenario after previous surgical repair of mitral regurgitation combining several treatment strategies for correction. METHODS AND RESULTS: Under general anaesthesia, and using echocardiographic as well as fluoroscopic guidance, a transseptal approach was carried out and two MitraClips were implanted at the level of A2/P2. At completion echocardiography, a new large regurgitation jet was observed in the centre of the anterior mitral leaflet. We decided to proceed with the implantation of an 8 mm AMPLATZER ASD septal occluder device (AMPLATZER Septal Occluder; St. Jude Medical, St. Paul, MN, USA) to seal the defect. This was accomplished and final echo showed remaining trivial regurgitation from the coaptation area, while the perforation was completely sealed. The patient was discharged in a clinically improved condition. Pre discharge transthoracic echocardiography showed the two MitraClips as well as the Amplatzer device in a stable correct position with trivial residual mitral regurgitation. CONCLUSIONS: The harmonisation of two diametral techniques for the treatment of recurring mitral regurgitation was effective in correcting the underlying problem. This approach may serve as an addition to the armamentarium of physicians treating patients with structural heart valve defects. PMID- 26865449 TI - Current decision making and short-term outcome in patients with degenerative aortic stenosis: the Pooled-RotterdAm-Milano-Toulouse In Collaboration Aortic Stenosis survey. AB - AIMS: The aim of this study was to provide a real-world snapshot of contemporary Heart Team decision making on patients with aortic stenosis (AS) and the consequent short-term clinical outcome. METHODS AND RESULTS: This was an international multicentre prospective registry encompassing 390 patients with symptomatic severe AS who were prospectively enrolled. Clinical endpoints and the decisive arguments to opt for surgical or transcatheter aortic valve replacement, or medical therapy were recorded separately. The mean age was 76.4+/-11.6 years, 55% were male and the STS score was 2.9% (IQR 1.6-6.9). The local Heart Teams considered 43%, 25% and 23% to be at low, intermediate and high operative risk with a calculated STS score of 2.18+/-1.72, 5.08+/-2.76 and 13.15+/-9.43, respectively. Overall, 7% were deemed inoperable. Ninety-four percent of patients at low operative risk were sent for SAVR whereas 64% and 92% of intermediate and high-risk patients underwent TAVI. Only 6% of patients did not receive any kind of aortic valve replacement. Overall, 30-day all-cause mortality was 2.8%. TAVI was associated with more major vascular complications, need for permanent pacemakers and post-procedural aortic regurgitation. SAVR had more life threatening bleedings and new-onset atrial fibrillation. CONCLUSIONS: The PRAGMATIC AS survey offers a snapshot of the contemporary management of patients with symptomatic severe AS. Multidisciplinary Heart Teams select an optimal strategy based on age, frailty and comorbidities. Nearly half of all patients are sent for TAVI. Only a small minority of patients will not receive valve replacement therapy. PMID- 26865450 TI - Real-world multicentre experience with the Direct Flow Medical repositionable and retrievable transcatheter aortic valve implantation system for the treatment of high-risk patients with severe aortic stenosis. AB - AIMS: Our aim was to assess the performance of the Direct Flow Medical (DFM) repositionable and retrievable transcatheter aortic valve implantation (TAVI) system in high-risk patients with severe aortic stenosis. METHODS AND RESULTS: One hundred and five consecutive high-risk patients with severe aortic stenosis undergoing TAVI with the DFM prosthesis were enrolled in six high-volume TAVI centres in Germany, Italy, The Netherlands, Belgium, and Luxembourg. The "inner curve" technique was systematically used in all patients. The primary endpoint was all-cause mortality at 30 days of clinical follow-up. Secondary endpoints for the same time frame were: (i) VARC-2-defined patient safety; and (ii) VARC-2 defined device success. The primary endpoint of all-cause mortality at 30 days was met in 1.9% (two patients). The VARC-2-defined device success rate was 98.1%. The combined patient safety endpoint was met in 88.6%. Residual moderate aortic regurgitation was observed in 1.9% (two patients). Permanent pacemaker implantation due to post-procedural persistent advanced atrioventricular block was performed in 9.5% (10 patients). CONCLUSIONS: In a multicentre, real-world clinical setting of high-risk patients with severe aortic stenosis, a repositionable and retrievable TAVI system was effective and safe in the short term follow-up. PMID- 26865451 TI - Edwards SAPIEN 3 implanted in a failing aortic bioprosthesis: first report. PMID- 26865452 TI - Tools and Techniques - Statistical. Estimating cumulative incidences in the presence of right-censoring and competing risks: an introduction with illustrations from the COACH study. PMID- 26865453 TI - How should I treat a chronic total occlusion of a saphenous vein graft? Successful retrograde revascularisation. PMID- 26865454 TI - A Critical Role of miR-144 in Diffuse Large B-cell Lymphoma Proliferation and Invasion. AB - MicroRNAs are endogenous noncoding RNAs that play important roles in a wide variety of biologic processes such as apoptosis, development, aging, and tumorigenesis. The B-cell lymphoma 6 (BCL6) transcriptional repressor has emerged as a critical therapeutic target in diffuse large B-cell lymphomas (DLBCL), but the mechanisms regulating BCL6 are still unclear. In the current study, we screened the microRNA expression profiles in DLBCL specimens and cell lines by qRT-PCR and found that the expression of miR-144 was significantly downregulated in DLBCL tissues and cell lines and negatively correlated with BCL6 expression. We further demonstrated that BCL6 was the direct target gene of miR-144, and miR 144 suppressed the expression of BCL6 via binding the 3'untranslated region of BCL6 mRNA. Biologically, forced expression of miR-144 significantly attenuated cell proliferation and invasion of OCI-Ly3 cells in vitro, and the tumor suppressor effect of miR-144 was also confirmed using a xenograft mouse model in vivo Taken together, our results reveal that miR-144 regulates BCL6 in DLBCL and provide a rationale for developing strategies that target miR-144 as a therapeutic intervention for DLBCL. PMID- 26865455 TI - Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer. AB - The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event. PMID- 26865457 TI - Magnetofluorescent micelles incorporating Dy(III)-DOTA as potential bimodal agents for optical and high field magnetic resonance imaging. AB - Dysprosium(iii) was coordinated to four 1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraacetic acid (DOTA) bisamide derivatives functionalized with amphiphilic p dodecylaniline and p-tetradecylaniline in a differing cis- and trans-orientation. The complexes were assembled into mono-disperse micelles having size distribution maxima ranging from 10 to 15 nm and the magnetic and optical properties of the micelles were examined in detail. The micelles show characteristic Dy(iii) emission with quantum yields reaching 0.8%. The transverse relaxivity r2 per Dy(iii) ion at 500 MHz and 310 K reaches maximum values of ca. 20 s(-1) mM(-1) which is a large increase when compared to a value of 0.8 s(-1) mM(-1) observed for Dy(III)-DTPA. The micelles were stable in water when incubated at 37 degrees C for 1 week and showed no relaxivity decrease when measured in the presence of 4% (w/v) human serum albumin. The efficient T2 relaxation, especially at strong magnetic fields, is sustained by the high magnetic moment of the dysprosium(iii) ion, the coordination of water molecules and long rotational correlation times. PMID- 26865458 TI - Personality expression in Chinese language use. AB - To date, little research has investigated personality expressions in languages other than English. Given that the Chinese language has the largest number of native speakers in the world, it is vitally important to examine the associations between personality and Chinese language use. In this research, we analysed Chinese microblogs and identified word categories and factorial structures associated with personality traits. We also compared our results with previous findings in English and showed that linguistic expression of personality has both universal- and language-specific aspects. Expression of personality via content words is more likely to be consistent across languages than expression via function words. This makes an important step towards uncovering universal patterns of personality expression in language. PMID- 26865456 TI - NK Cell-Mediated Antitumor Effects of a Folate-Conjugated Immunoglobulin Are Enhanced by Cytokines. AB - Optimally effective antitumor therapies would not only activate immune effector cells but also engage them at the tumor. Folate conjugated to immunoglobulin (F IgG) could direct innate immune cells with Fc receptors to folate receptor expressing cancer cells. F-IgG bound to human KB and HeLa cells, as well as murine L1210JF, a folate receptor (FR)-overexpressing cancer cell line, as determined by flow cytometry. Recognition of F-IgG by natural killer (NK) cell Fc receptors led to phosphorylation of the ERK transcription factor and increased NK cell expression of CD69. Lysis of KB tumor cells by NK cells increased by about 5 fold after treatment with F-IgG, an effect synergistically enhanced by treatment with IL2, IL12, IL15, or IL21 (P< 0.001). F-IgG also enhanced the lysis of chronic lymphocytic leukemia cells by autologous NK cells. NK cells significantly increased production of IFNgamma, MIP-1alpha, and RANTES in response to F-IgG coated KB target cells in the presence of the NK cell-activating cytokine IL12, and these coculture supernatants induced significant T-cell chemotaxis (P< 0.001). F-IgG-coated targets also stimulated FcR-mediated monocyte effector functions. Studies in a murine leukemia model confirmed the intratumoral localization and antitumor activity of F-IgG, as well as enhancement of its effects by IL12 (P =0.05). The antitumor effect of this combination was dependent on NK cells and led to decreased tumor cell proliferation in vivo Thus, F-IgG can induce an immune response against FR-positive tumor cells that is mediated by NK cells and can be augmented by cytokine therapy. PMID- 26865459 TI - Scavenger receptor B1, the HDL receptor, is expressed abundantly in liver sinusoidal endothelial cells. AB - Cholesterol from peripheral tissue, carried by HDL, is metabolized in the liver after uptake by the HDL receptor, SR-B1. Hepatocytes have long been considered the only liver cells expressing SR-B1; however, in this study we describe two disparate immunofluorescence (IF) experiments that suggest otherwise. Using high resolution confocal microscopy employing ultrathin (120 nm) sections of mouse liver, improving z-axis resolution, we identified the liver sinusoidal endothelial cells (LSEC), marked by FcgammaRIIb, as the cell within the liver expressing abundant SR-B1. In contrast, the hepatocyte, identified with beta catenin, expressed considerably weaker levels, although optical resolution of SR B1 was inadequate. Thus, we moved to a different IF strategy, first separating dissociated liver cells by gradient centrifugation into two portions, hepatocytes (parenchymal cells) and LSEC (non-parenchymal cells). Characterizing both portions for the cellular expression of SR-B1 by flow cytometry, we found that LSEC expressed considerable amounts of SR-B1 while in hepatocytes SR-B1 expression was barely perceptible. Assessing mRNA of SR-B1 by real time PCR we found messenger expression in LSEC to be about 5 times higher than in hepatocytes. PMID- 26865460 TI - Serially Transplanted Nonpericytic CD146(-) Adipose Stromal/Stem Cells in Silk Bioscaffolds Regenerate Adipose Tissue In Vivo. AB - Progenitors derived from the stromal vascular fraction (SVF) of white adipose tissue (WAT) possess the ability to form clonal populations and differentiate along multiple lineage pathways. However, the literature continues to vacillate between defining adipocyte progenitors as "stromal" or "stem" cells. Recent studies have demonstrated that a nonpericytic subpopulation of adipose stromal cells, which possess the phenotype, CD45(-) /CD31(-) /CD146(-) /CD34(+) , are mesenchymal, and suggest this may be an endogenous progenitor subpopulation within adipose tissue. We hypothesized that an adipose progenitor could be sorted based on the expression of CD146, CD34, and/or CD29 and when implanted in vivo these cells can persist, proliferate, and regenerate a functional fat pad over serial transplants. SVF cells and culture expanded adipose stromal/stem cells (ASC) ubiquitously expressing the green fluorescent protein transgene (GFP-Tg) were fractionated by flow cytometry. Both freshly isolated SVF and culture expanded ASC were seeded in three-dimensional silk scaffolds, implanted subcutaneously in wild-type hosts, and serially transplanted. Six-week WAT constructs were removed and evaluated for the presence of GFP-Tg adipocytes and stem cells. Flow cytometry, quantitative polymerase chain reaction, and confocal microscopy demonstrated GFP-Tg cell persistence, proliferation, and expansion, respectively. Glycerol secretion and glucose uptake assays revealed GFP-Tg adipose was metabolically functional. Constructs seeded with GFP-Tg SVF cells or GFP-Tg ASC exhibited higher SVF yields from digested tissue, and higher construct weights, compared to nonseeded controls. Constructs derived from CD146(-) CD34(+) -enriched GFP-Tg ASC populations exhibited higher hemoglobin saturation, and higher frequency of GFP-Tg cells than unsorted or CD29(+) GFP-Tg ASC counterparts. These data demonstrated successful serial transplantation of nonpericytic adipose-derived progenitors that can reconstitute adipose tissue as a solid organ. These findings have the potential to provide new insights regarding the stem cell identity of adipose progenitor cells. PMID- 26865463 TI - What Is the Best Method to Fit Time-Resolved Data? A Comparison of the Residual Minimization and the Maximum Likelihood Techniques As Applied to Experimental Time-Correlated, Single-Photon Counting Data. AB - The need for measuring fluorescence lifetimes of species in subdiffraction limited volumes in, for example, stimulated emission depletion (STED) microscopy, entails the dual challenge of probing a small number of fluorophores and fitting the concomitant sparse data set to the appropriate excited-state decay function. This need has stimulated a further investigation into the relative merits of two fitting techniques commonly referred to as "residual minimization" (RM) and "maximum likelihood" (ML). Fluorescence decays of the well-characterized standard, rose bengal in methanol at room temperature (530 +/- 10 ps), were acquired in a set of five experiments in which the total number of "photon counts" was approximately 20, 200, 1000, 3000, and 6000 and there were about 2 200 counts at the maxima of the respective decays. Each set of experiments was repeated 50 times to generate the appropriate statistics. Each of the 250 data sets was analyzed by ML and two different RM methods (differing in the weighting of residuals) using in-house routines and compared with a frequently used commercial RM routine. Convolution with a real instrument response function was always included in the fitting. While RM using Pearson's weighting of residuals can recover the correct mean result with a total number of counts of 1000 or more, ML distinguishes itself by yielding, in all cases, the same mean lifetime within 2% of the accepted value. For 200 total counts and greater, ML always provides a standard deviation of <10% of the mean lifetime, and even at 20 total counts there is only 20% error in the mean lifetime. The robustness of ML advocates its use for sparse data sets such as those acquired in some subdiffraction-limited microscopies, such as STED, and, more importantly, provides greater motivation for exploiting the time-resolved capacities of this technique to acquire and analyze fluorescence lifetime data. PMID- 26865462 TI - Combined toxicity of heavy metal mixtures in liver cells. AB - With rapid industrialization, China is now facing great challenges in heavy metal contamination in the environment. Human exposure to heavy metals through air, water and food commonly involves a mixture consisting of multiple heavy metals. In this study, eight common heavy metals (Pb, Cd, Hg, Cu, Zn, Mn, Cr, Ni) that cause environmental contamination were selected to investigate the combined toxicity of different heavy metal mixtures in HL7702 cells. Toxicity (24 h LC50 ) of each individual metal on the cells ranked Hg > Cr = Cd > Cu > Zn > Ni > Mn > Pb; toxicity of the different mixtures ranked: M5 > M3PbHgCd > M5+Mn > M5+Cu > M2CdNi > M4A > M8-Mn > M8 > M5+Zn > M4B > M8-Cr > M8-Zn > M8-Cu > M8-Pb > M8-Cd > M8-Hg > M8-Ni > M3PbHgNi > M3CuZnMn. The cytotoxicity data of individual metals were successfully used to build the additive models of two- to eight-component metal mixtures. The comparison between additive model and combination model or partly additive model was useful to evaluate the combined effects in mixture. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures. These results suggest that the combined effects should be considered in the risk assessment of heavy metal co-exposure, and more comprehensive investigations on the combined effects of different heavy metal mixtures are needed in the future. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26865461 TI - Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling. AB - G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like peptides, hormones, lipids, and neurotransmitters activate second messengers and induce several biological responses by binding to these seven transmembrane receptors, which are coupled to heterotrimeric G proteins. Recently, additional molecular mechanisms have been involved in GPCR-mediated signaling, leading to an intricate network of transduction pathways. In this regard, it should be mentioned that diverse GPCR family members contribute to the adaptive cell responses to low oxygen tension, which is a distinguishing feature of several illnesses like neoplastic and cardiovascular diseases. For instance, the G protein estrogen receptor, namely G protein estrogen receptor (GPER)/GPR30, has been shown to contribute to relevant biological effects induced by hypoxia via the hypoxia-inducible factor (HIF) 1alpha in diverse cell contexts, including cancer. Likewise, GPER has been found to modulate the biological outcome of hypoxic/ischemic stress in both cardiovascular and central nervous systems. Here, we describe the role exerted by GPCR-mediated signaling in low oxygen conditions, discussing, in particular, the involvement of GPER by a hypoxic microenvironment. PMID- 26865464 TI - Regulatory mechanisms, expression levels and proliferation effects of the FUS DDIT3 fusion oncogene in liposarcoma. AB - Fusion oncogenes are among the most common types of oncogene in human cancers. The gene rearrangements result in new combinations of regulatory elements and functional protein domains. Here we studied a subgroup of sarcomas and leukaemias characterized by the FET (FUS, EWSR1, TAF15) family of fusion oncogenes, including FUS-DDIT3 in myxoid liposarcoma (MLS). We investigated the regulatory mechanisms, expression levels and effects of FUS-DDIT3 in detail. FUS-DDIT3 showed a lower expression than normal FUS at both the mRNA and protein levels, and single-cell analysis revealed a lack of correlation between FUS-DDIT3 and FUS expression. FUS-DDIT3 transcription was regulated by the FUS promotor, while its mRNA stability depended on the DDIT3 sequence. FUS-DDIT3 protein stability was regulated by protein interactions through the FUS part, rather than the leucine zipper containing DDIT3 part. In addition, in vitro as well as in vivo FUS-DDIT3 protein expression data displayed highly variable expression levels between individual MLS cells. Combined mRNA and protein analyses at the single-cell level showed that FUS-DDIT3 protein expression was inversely correlated to the expression of cell proliferation-associated genes. We concluded that FUS-DDIT3 is uniquely regulated at the transcriptional as well as the post-translational level and that its expression level is important for MLS tumour development. The FET fusion oncogenes are potentially powerful drug targets and detailed knowledge about their regulation and functions may help in the development of novel treatments. PMID- 26865467 TI - Effect of Asthma Call-back Survey methodology changes on work-related asthma estimates, 19 states, 2007-2012. AB - OBJECTIVE: Asthma Call-back Survey methodology has been changed recently, as a new sampling design, weights calculation (2011-2012), and revised work-related asthma (WRA) section (2012) were implemented. To assess the effect of these changes on the WRA and possible WRA estimates among ever-employed adults with current asthma, we analyzed 2007-2012 data for 37 505 ever-employed adults (>=18 years) collected from 19 US states (representing an estimated 10 million adults each year). METHODS: Using data from landline telephone (LLP) households, we calculated estimates applying poststratification weights (2007-2010) and "raking" weights (2011-2012). Also, using data from LLP/cellular telephone (CP) households combined, we calculated estimates applying "raking" weights (2012). RESULTS: Based on LLP household data, the WRA estimates ranged from 7.8% to 9.7% during 2007-2010, was 9.1% in 2011 and 15.4% in 2012. Possible WRA estimates ranged from 35.1% to 38.1% during 2007-2010, was 38.1% in 2011 and 39.8% in 2012. Using the 2012 LLP/CP household data, the WRA and possible WRA estimates were 15.4% and 38.9%, respectively. CONCLUSIONS: Implementation of "raking" weights did not substantially change the WRA or possible WRA estimates among ever-employed adults with current asthma. The WRA and possible WRA estimates based on LLP and LLP/CP samples in 2012 were comparable, as CP users are younger and less likely to have WRA. The substantial upward shift in the 2012 WRA estimates likely was associated with the revision to the WRA section. PMID- 26865469 TI - List of new names and new combinations previously effectively, but not validly, published. PMID- 26865468 TI - Accurate Extraction of Nanometer Distances in Multimers by Pulse EPR. AB - Pulse electron paramagnetic resonance (EPR) is gaining increasing importance in structural biology. The PELDOR (pulsed electron-electron double resonance) method allows extracting distance information on the nanometer scale. Here, we demonstrate the efficient extraction of distances from multimeric systems such as membrane-embedded ion channels where data analysis is commonly hindered by multi spin effects. PMID- 26865471 TI - The Impact of Medicare Part D on Emergency Department Visits. AB - The Medicare Part D program introduced prescription drug coverage for seniors in 2006. We examine the impact of this program on the use of emergency department (ED) care. Using a difference-in-differences model, we find declines in the number of ED visits for non-emergency care but not for emergency care, suggesting that Part D may have led to better management of health and reduced unnecessary use of EDs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26865470 TI - Mechanism of Developmental Effects in Rats Caused by an N-Phenylimide Herbicide: Transient Fetal Anemia and Sequelae during Mid-to-Late Gestation. AB - BACKGROUND: Rat developmental toxicity including embryolethality and teratogenicity (mainly ventricular septal defects [VSDs] and wavy ribs) was produced by an N-phenylimide herbicide that inhibits protoporphyrinogen oxidase (PPO) common to chlorophyll and heme biosynthesis. Major characteristics of the developmental toxicity included species difference between rats and rabbits, compound-specific difference among structurally similar herbicides, and sensitive period. Protoporphyrin accumulation in treated fetuses closely correlated with the major characteristics. Iron deposits in erythroblastic mitochondria and degeneration of erythroblasts were observed in treated rat fetuses. In this study we investigated fetal anemia and subsequent developmental effects in rats, and inhibition of PPO in rats, rabbits, and humans by the herbicides in vitro. METHODS: Fetuses were treated on gestational day (GD) 12 and removed on GDs 13 through 20. All litters were examined externally. One half of litters were examined for blood and skeletal development, and the other half for interventricular foramen closure. Effects on PPO were determined in mitochondria from embryos and adult livers. RESULTS: Fetal anemia in rats was evident on GDs 13 through 16. Subsequently, enlarged heart, delayed closure of the foramen, reduced serum protein, and retarded rib ossification were observed. In vitro PPO inhibition exhibited species- and compound-specific differences corresponding to the developmental toxicity. CONCLUSION: We propose that developmental toxicity results from PPO inhibition in primitive erythroblasts, causing transient fetal anemia followed by death. Compensatory enlargement of the fetal heart results in failure of interventricular foramen closure and VSD. Reduced serum protein leads to delayed ossification and wavy ribs. PMID- 26865472 TI - Dose-Dependent Flux of Buprenorphine Following Transdermal Administration in Healthy Subjects. AB - Buprenorphine transdermal delivery system (BTDS) applied once every 7 days is indicated for the management of pain that is severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. The 7-day flux of buprenorphine from BTDS to systemic circulation was investigated in a phase 1, 2-period crossover study with 3 randomized groups of healthy subjects receiving BTDS containing buprenorphine 5, 10, or 20 mg for 7 days preceded or followed by intravenous buprenorphine infusion (25 MUg/h for 24 hours). Residual and absolute bioavailability methods were used to estimate 7-day flux of buprenorphine. Following BTDS administration, mean area under the curve of buprenorphine increased proportionally (12.6, 24.3, and 51.1 ng/[mL . h]), maximum mean plasma concentration rose with increasing dose (176, 191, and 471 pg/mL), and absolute bioavailability was 14% to 16%. Mean residual amount of buprenorphine in the BTDS after 7-day application was 4.50, 8.57, and 17.1 mg. Flux of buprenorphine was approximately 5, 10, and 20 MUg/h for BTDS containing 5, 10, and 20 mg buprenorphine, respectively. BTDS was safe and well tolerated following a single 7-day application in healthy subjects. The results of this study demonstrated dose-dependent flux of buprenorphine delivered via transdermal system. PMID- 26865473 TI - Stable -ESiMe3 Complexes of Cu(I) and Ag(I) (E=S, Se) with NHCs: Synthons in Ternary Nanocluster Assembly. AB - As a part of efforts to prepare new "metallachalcogenolate" precursors and develop their chemistry for the formation of ternary mixed-metal chalcogenide nanoclusters, two sets of thermally stable, N-heterocyclic carbene metal chalcogenolate complexes of the general formula [(IPr)Ag-ESiMe3] (IPr=1,3-bis(2,6 diisopropylphenyl)imidazolin-2-ylidene; E=S, 1; Se, 2) and [(iPr2-bimy)Cu ESiMe3]2 (iPr2-bimy=1,3-diisopropylbenzimidazolin-2-ylidene; E=S, 4; Se, 5) are reported. These are prepared from the reaction between the corresponding carbene metal acetate, [(IPr)AgOAc] and [(iPr-bimy)CuOAc] respectively, and E(SiMe3 )2 at low temperature. The reaction of [(IPr)Ag-ESiMe3] 1 with mercury(II) acetate affords the heterometallic complex [{(IPr)AgS}2Hg] 3 containing two (IPr)Ag-S(-) fragments bonded to a central Hg(II), representing a mixed mercury-silver sulfide complex. The reaction of [(iPr2-bimy)Cu-SSiMe3]2, which contains a smaller N heterocyclic-carbene, with mercuric(II) acetate affords the high nuclearity cluster, [(iPr2-bimy)6Cu10S8Hg3]6. The new N-heterocyclic carbene metal chalcogenolate complexes 1, 2, 4, 5 and the ternary mixed-metal chalcogenolate complex 3 and cluster 6 have been characterized by multinuclear NMR spectroscopy ((1)H and (13)C), elemental analysis and single-crystal X-ray diffraction. PMID- 26865474 TI - Redesigning Care for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: The "Shock Team". PMID- 26865475 TI - Plantar subcutaneous sarcoidosis - a rare form of skin sarcoidosis: unusual plantar aponeurosis location of sarcoidosis as primary manifestation of asymptomatic systemic disease. PMID- 26865476 TI - Zika Virus Infection and the Eye. PMID- 26865477 TI - Intermittent PQ prolongation between two premature ventricular complexes: what is the mechanism? PMID- 26865478 TI - Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure. AB - AIMS: Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. METHODS AND RESULTS: Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction <=40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. CONCLUSION: Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship. PMID- 26865479 TI - Reduced sulfentrazone phytotoxicity through increased adsorption and anionic species in biochar-amended soils. AB - Burning straw in the field is a common agricultural practice. The effects of adding biochar derived from rice straw to soils on the phytotoxicity of sulfentrazone to Oryza sativa L. were observed. Overall, when 1 % biochar was added to three different soils, the phytotoxicity of sulfentrazone to O. sativa L. decreased, and the concentration that inhibits growth by 50 % (IC50) increased by 1.4 to 7.6 times. To illuminate the influencing mechanisms, the changes in sulfentrazone adsorption to the soil, the soil pH, and the bioavailable sulfentrazone extracted from the soil solution using hollow fiber-based liquid phase microextraction were studied. The Freundlich constant (K f ) of sulfentrazone to the soil increased 1.5 to 25 times relative to the K f in the three unamended soils, and the soil pH increased by 0.36 to 1.36 units resulted in a fraction of dissociated sulfentrazone increased by 10.2-17.4 %. In addition, the average concentrations of sulfentrazone in the three unamended soil solutions were 1.3-6.1 times relative to those in the three biochar-amended soil solutions. These results suggest that the sulfentrazone adsorption and soil pH increased when soils were amended with biochar, which decreased the bioavailable concentrations and reduced its phytotoxicity to O. sativa L. PMID- 26865480 TI - The effect of U speciation in cultivation solution on the uptake of U by variant Sedum alfredii. AB - In the present study, five plant species were screened for uranium uptake using a hydroponic experimental set-up. The effect of the U concentration, pH, as well as the presence of carbonates, phosphates, and organic acids (lactic acid, malic acid, citric acid) on the uptake of U by variant S. alfredii (V S. alfredii) and wild S. alfredii (W S. alfredii) were investigated. Results showed that V S. alfredii exhibited higher U content in the roots than the other four plants and with the increase of U concentration in the solution, the U uptake by V S. alfredii and W S. alfredii increased. The results also showed that different U speciation in different cultivation solution took an important role on the uptake of U in variant Sedum alfredii: at pH 6.5, U hydrolysis species (UO2)3(OH)5 (+)is predominant and the U concentrations in V S. alfredii roots reached a maximum value (3.7 * 10(4) mg/kg). U complexation with carbonates, phosphates, and some organic acids in the solution resulted in a decrease in the U content in the roots except for lactic acid. Our researches highlight the correlations between U speciation and the uptake on V S. Alfredii, which will be helpful for improved removal of U from the groundwater using phytoremediation method. PMID- 26865481 TI - Coupling of bio-PRB and enclosed in-well aeration system for remediation of nitrobenzene and aniline in groundwater. AB - A laboratory-scale bio-permeable reactive barrier (bio-PRB) was constructed and combined with enclosed in-well aeration system to treat nitrobenzene (NB) and aniline (AN) in groundwater. Batch-style experiments were first conducted to evaluate the effectiveness of NB and AN degradation, using suspension (free cells) of degrading consortium and immobilized consortium by a mixture of perlite and peat. The NB and AN were completely degraded in <3 days using immobilized consortium, while 3-5 days were required using free cells. The O2 supply efficiency of an enclosed in-well aeration system was assessed in a box filled with perlite and peat. Dissolved O2 (DO) concentrations increased to 8-12 mg L( 1) in 12 h for sampling ports within 12 cm of the aeration well. A diffusion coefficient as 33.5 cm(2) s(-1) was obtained. The DO concentration was >4 mg L( 1) when the aeration system was applied into the bio-PRB system. The NB and AN were effectively removed when the aeration system was functional in the bio-PRB. The removal efficiency decreased when the aeration system malfunctioned for 20 days, thus indicating that DO was an important factor for the degradation of NB and AN. The regain of NB and AN removal after the malfunction indicates the robustness of degradation consortium. No original organics and new formed by products were observed in the effluent. The results indicate that NB and AN in groundwater can be completely mineralized in a bio-PRB equipped with enclosed in well aeration system and filled with perlite and peat attached with degrading consortium. PMID- 26865482 TI - Antibiotic concentration and antibiotic-resistant bacteria in two shallow urban lakes after stormwater event. AB - Stormwater runoff is generally characterized as non-point source pollution. In the present study, antibiotic concentration and antibiotic susceptibilities of cultivable heterotrophic bacteria were investigated in two small shallow urban lakes before and after strong storm event. Several antibiotics, lactose fermenting bacteria and cultivable heterotrophic bacteria concentrations increased in surface water and/or surface sediment of two small urban lakes (Lake Xuanwu and Wulongtan) after strong storm event. In general, the frequencies of bacteria showing resistance to nine antibiotics increased after storm event. Based on the 16S rRNA genes of 50 randomly selected isolates from each water sample of two lakes, Aeromonas and Bacillus were dominant genera in samples from two lakes, while genera Proteus and Lysinibacillus were the third abundant genera in Lake Xuanwu and Wulongtu, respectively. Presences of nine antibiotic resistance genes (ARGs) in the 100 isolates were detected and most of these isolates harbored at least two ARGs with different functions. The detection frequency of ARGs in Gram-negative isolates was higher than that in Gram-positive isolates. The most prevalent integron in 100 isolates was int(II) (n = 28), followed by int(I) (n = 17) and int(III) (n = 17). Our results indicate that strong storm events potentially contribute to the transfer of ARGs and antibiotic resistant bacteria from land-sewer system to the urban Lakes. PMID- 26865483 TI - Distribution and diversity of biosurfactant-producing bacteria in a wastewater treatment plant. AB - The distribution and diversity of culturable biosurfactant-producing bacteria were investigated in a wastewater treatment plant (WWTP) using the Shannon and Simpson's indices. Twenty wastewater samples were analysed, and from 667 isolates obtained, 32 were classified as biosurfactant producers as they reduced the surface tension of the culture medium (71.1 mN/m), with the lowest value of 32.1 mN/m observed. Certain isolates also formed stable emulsions with diesel, kerosene and mineral oils. The 16S ribosomal RNA (rRNA) analysis classified the biosurfactant producers into the Aeromonadaceae, Bacillaceae, Enterobacteriaceae, Gordoniaceae and the Pseudomonadaceae families. In addition, numerous isolates carried the surfactin 4'-phosphopantetheinyl transferase (sfp), rhamnosyltransferase subunit B (rhlB) and bacillomycin C (bamC) genes involved in the biosynthesis of surfactin, rhamnolipid and bacillomycin, respectively. While, biosurfactant-producing bacteria were found at all sampling points in the WWTP, the Simpson's diversity (1 - D) and the Shannon-Weaver (H) indices revealed an increase in bacterial diversity in the influent samples (0.8356 and 2.08), followed by the effluent (0.8 and 1.6094) and then the biological trickling filter (0.7901 and 1.6770) samples. Numerous biosurfactant-producing bacteria belonging to diverse genera are thus present throughout a WWTP. PMID- 26865484 TI - Optimized treatment conditions for textile wastewater reuse using photocatalytic processes under UV and visible light sources. AB - In this study, photo-Fenton systems using visible light sources with iron and ferrioxalate were tested for the DOC degradation and decolorization of textile wastewater. Textile wastewaters originated after the dyeing stage of dark-colored tissue in the textile industry, and the optimization of treatment processes was studied to produce water suitable for reuse. Dissolved organic carbon, absorbance, turbidity, anionic concentrations, carboxylic acids, and preliminary cost analysis were performed for the proposed treatments. Conventional photo Fenton process achieved near 99 % DOC degradation rates and complete absorbance removal, and no carboxylic acids were found as products of degradation. Ferrioxalate photo-Fenton system achieved 82 % of DOC degradation and showed complete absorbance removal, and oxalic acid has been detected through HPLC analysis in the treated sample. In contrast, photo-peroxidation with UV light was proved effective only for absorbance removal, with DOC degradation efficiency near 50 %. Treated wastewater was compared with reclaimed water and had a similar quality, indicating that these processes can be effectively applied for textile wastewater reuse. The results of the preliminary cost analysis indicated costs of 0.91 to 1.07 US$ m-3 for the conventional and ferrioxalate photo-Fenton systems, respectively. Graphical Abstract ?. PMID- 26865485 TI - Physiological basis of differential zinc and copper tolerance of Verbascum populations from metal-contaminated and uncontaminated areas. AB - Metal contamination represents a strong selective pressure favoring tolerant genotypes and leading to differentiation between plant populations. We investigated the adaptive capacity of early-colonizer species of Verbascum recently exposed to Zn- and Cu-contaminated soils (10-20 years). Two Verbascum thapsus L. populations from uncontaminated sites (NMET1, NMET2), one V. thapsus from a zinc-contaminated site (MET1), and a Verbascum lychnitis population from an open-cast copper mine (MET2) were exposed to elevated Zn or Cu in hydroponic culture under glasshouse conditions. MET populations showed considerably higher tolerance to both Zn and Cu than NMET populations as assessed by measurements of growth and net photosynthesis, yet they accumulated higher tissue Zn concentrations in the shoot. Abscisic acid (ABA) concentration increased with Zn and Cu treatment in the NMET populations, which was correlated to stomatal closure, decrease of net photosynthesis, and nutritional imbalance, indicative of interference with xylem loading and divalent-cation homeostasis. At the cellular level, the sensitivity of NMET2 to Zn and Cu was reflected in significant metal induced ROS accumulation and ion leakage from roots as well as strong induction of peroxidase activity (POD, EC 1.11.1.7), while Zn had no significant effect on ABA concentration and POD activity in MET1. Interestingly, MET2 had constitutively higher root ABA concentration and POD activity. We propose that ABA distribution between shoots and roots could represent an adaptive mechanism for maintaining low ABA levels and unaffected stomatal conductance. The results show that metal tolerance can occur in Verbascum populations after relatively short time of exposure to metal-contaminated soil, indicating their potential use for phytostabilization. PMID- 26865486 TI - Effects of the addition of iron and aluminum salt on phosphorus adsorption in wetland sediment. AB - Adsorption and removal of phosphorus (P) in wetland sediment from aqueous solutions were investigated by using four kinds of iron (Fe) and aluminum (Al) salt (FeCl3, AlCl3, poly FeCl3, and poly AlCl3). Under optimal temperature of 25 degrees C, P concentration of 50 mg/L, and mole concentration ratio of 4:1 (Fe(3+)/PO4 (3-) or Al(3+)/PO4 (3-)), the P sorption capacities of wetland sediments by FeCl3, poly FeCl3, AlCl3, and poly AlCl3treatments were 296.03, 371.41, 276.3, and 357.85 MUg/g, respectively, and were enhanced by 83.36, 158.74, 63.63, and 145.18 MUg/g, respectively. The P sorption capacities based on different additives were in the order of poly FeCl3 > poly AlCl3 > FeCl3 > AlCl3. The EPC0 values, K values, and maximum adsorption capacities indicated that poly FeCl3 was good reagent to restore P pollution in aqueous solution by wetland sediment in the consideration of both P treatment efficiency and potential environmental impact. These findings, obviously, are useful basis to develop new effective methods for P removal in waters. PMID- 26865487 TI - Cd immobilization in a contaminated rice paddy by inorganic stabilizers of calcium hydroxide and silicon slag and by organic stabilizer of biochar. AB - A field experiment was conducted in a Cd-contaminated rice paddy field to evaluate the effect of inorganic and organic metal stabilizers on Cd mobility and rice uptake. A dose of inorganic stabilizer of calcium hydroxide (CH), silicon slag (SS), and wheat straw biochar (BC) was amended respectively to topsoil before rice transplanting. Rice production was managed with the same water regime and fertilization practices consistently between treatments including a control without amendment. Samples of topsoil and rice plant were collected at rice harvest to analyze the Cd mobility and uptake by rice. Without affecting rice grain yield, the stabilizers significantly decreased CaCl2-extractable Cd in a range of 44 to 75 % compared to the control, corresponding to soil pH changes under the different treatments. Accordingly, Cd concentrations both in rice tissue and in rice grain were very significantly decreased under these treatments. The decrease in rice Cd uptake was correlated to the decrease in extractable Cd, which was again correlated to soil pH change under the different treatments, indicating a prevalent role of liming effect by the amendments. While applied at a large amount in a single year, organic stabilizer of BC decreased Cd extractability by up to 43 % and Cd rice uptake by up to 61 %, being the most effective on Cd immobilization. However, the long-term effect on soil health and potential tradeoff effects with different stabilizers deserve further field monitoring studies. PMID- 26865489 TI - Hydrothermal electrocatalytic oxidation for the treatment of herbicides wastewater. AB - A hydrothermal electrocatalytic oxidation (HTECO) method is adopted to treat the biorefractory and toxic 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides wastewater on nano-Pt/Ti electrode in the existence of H2O2. Comparisons for the removal of 2,4-D and total organic carbon (TOC) have been carried out between HTECO with individual electrochemical oxidation (EO) and hydrothermal catalytic oxidation (HTCO), showing that high mineralization efficiency was obtained in HTECO process. The possible factors resulting in the high removal efficiency in HTECO process have been studied by investigating the properties of the electrode and solution in hydrothermal condition, the amount of active radicals, the decay kinetic, and evolution of main intermediates of 2,4-D. Thus, an enhanced mechanism for HTECO method for the treatment of herbicides wastewater has been obtained. PMID- 26865488 TI - Microcystin-tolerant Rhizobium protects plants and improves nitrogen assimilation in Vicia faba irrigated with microcystin-containing waters. AB - Irrigation of crops with microcystins (MCs)-containing waters-due to cyanobacterial blooms-affects plant productivity and could be a way for these potent toxins entering the food chain. This study was performed to establish whether MC-tolerant rhizobia could benefit growth, nodulation, and nitrogen metabolism of faba bean plants irrigated with MC-containing waters. For that, three different rhizobial strains-with different sensitivity toward MCs-were used: RhOF96 (most MC-sensitive strain), RhOF125 (most MC-tolerant strain), or Vicz1.1 (reference strain). As a control, plants grown without rhizobia and fertilized by NH4NO3 were included in the study. MC exposure decreased roots (30 37 %) and shoots (up to 15 %) dry weights in un-inoculated plants, whereas inoculation with rhizobia protects plants toward the toxic effects of MCs. Nodulation and nitrogen content were significantly impaired by MCs, with the exception of plants inoculated with the most tolerant strain RhOF125. In order to deep into the effect of inoculation on nitrogen metabolism, the nitrogen assimilatory enzymes (glutamine synthetase (GS) and glutamate synthase (GOGAT)) were investigated: Fertilized plants showed decreased levels (15-30 %) of these enzymes, both in shoots and roots. By contrast, inoculated plants retained the levels of these enzymes in shoots and roots, as well as the levels of NADH-GOGAT activity in nodules. We conclude that the microcystin-tolerant Rhizobium protects faba bean plants and improves nitrogen assimilation when grown in the presence of MCs. PMID- 26865490 TI - Phytoremediation of crude oil-contaminated soil employing Crotalaria pallida Aiton. AB - The purpose of the study was to evaluate the phytoremediation potentiality of a herb named Crotalaria pallida which are abundantly grown on crude oil contaminated soil of oil field situated at upper Assam, India, so that this plant could be used to remediate hydrocarbon from contaminated soil. To evaluate the potentiality of the plant, a pot culture experiment was conducted taking 3 kg of rice field soil mixed with crude oil at a concentration of 10,000 (10 g/kg), 20,000 (20 g/kg), 30,000 (30 g/kg), 40,000 (40 g/kg), 50,000 (50 g/kg), 60,000 (60 g/kg), 70,000 (70 g/kg), 80,000 (80 g/kg), 90,000 (90 g/kg), and 100,000 (100 g/kg) ppm. Ten numbers of healthy seeds of C. pallida were sown in three pots of each concentration for germination, and after 15 days of germination, single healthy seedling in each pot was kept for the study. A control setup was also maintained without adding crude oil. The duration of the experiment was fixed for 6 months. The results showed that uptake of hydrocarbon by the plants was increased with increasing the concentration of crude oil in the soil up to 60,000 ppm. After that, uptake of hydrocarbon by the plants was found to be lower with increasing doses of crude oil concentration. Uptake of hydrocarbon by the shoot was found to be maximum, i.e., 35,018 ppm in 60,000 ppm concentration. Dissipation of total petroleum hydrocarbon (TPH) from the soil was also gradually increased with increasing concentration of crude oil in the soil up to 60,000 ppm. Maximum dissipation, i.e., 78.66 %, occurred in 60,000 ppm concentration of crude oil-mixed soil. The plant could not survive in 100,000 ppm concentration of crude oil-mixed soil. The results also demonstrated that there was a reduction in plant shoot and root biomass with an increase of crude oil concentration. Furthermore, results revealed that the shoot biomass was higher than root biomass in all the treatments. PMID- 26865491 TI - Volcano-related materials in concretes: a comprehensive review. AB - Massive volcano-related materials (VRMs) erupted from volcanoes bring the impacts to natural environment and humanity health worldwide, which include generally volcanic ash (VA), volcanic pumice (VP), volcanic tuff (VT), etc. Considering the pozzolanic activities and mechanical characters of these materials, civil engineers propose to use them in low carbon/cement and environment-friendly concrete industries as supplementary cementitious materials (SCMs) or artificial/natural aggregates. The utilization of VRMs in concretes has attracted increasing and pressing attentions from research community. Through a literature review, this paper presents comprehensively the properties of VRMs and VRM concretes (VRMCs), including the physical and chemical properties of raw VRMs and VRMCs, and the fresh, microstructural and mechanical properties of VRMCs. Besides, considering environmental impacts and the development of long-term properties, the durability and stability properties of VRMCs also are summarized in this paper. The former focuses on the resistance properties of VRMCs when subjected to aggressive environmental impacts such as chloride, sulfate, seawater, and freezing-thawing. The latter mainly includes the fatigue, creep, heat-insulating, and expansion properties of VRMCs. This study will be helpful to promote the sustainability in concrete industries, protect natural environment, and reduce the impacts of volcano disaster. Based on this review, some main conclusions are discussed and important recommendations regarding future research on the application of VRMs in concrete industries are provided. PMID- 26865492 TI - Characterization of chromophoric dissolved organic matter and relationships among PARAFAC components and water quality parameters in Heilongjiang, China. AB - Chromophoric dissolved organic matter (CDOM) is an important optically active substance that can transports nutrients and pollutants from terrestrial to aquatic systems. Additionally, it is used as a measure of water quality. To investigate the source and composition of CDOM, we used chemical and fluorescent analyses to characterize CDOM in Heilongjiang. The composition of CDOM can be investigated by excitation-emission matrix (EEM) fluorescence and parallel factor analysis (PARAFAC). PARAFAC identified four individual components that were attributed to microbial humic-like (C1) and terrestrial humic-like (C2-4) in water samples collected from the Heilongjiang River. The relationships between the maximum fluorescence intensities of the four PARAFAC components and the water quality parameters indicate that the dynamic of the four components is related to nutrients in the Heilongjiang River. The relationships between the fluorescence component C3 and the biochemical oxygen demand (BOD5) indicates that component C3 makes a great contribution to BOD5 and it can be used as a carbon source for microbes in the Heilongjiang River. Furthermore, the relationships between component C3, the particulate organic carbon (POC), and the chemical oxygen demand (CODMn) show that component C3 and POC make great contributions to BOD5 and CODMn. The use of these indexes along with PARAFAC results would be of help to characterize the co-variation between the CDOM and water quality parameters in the Heilongjiang River. PMID- 26865493 TI - Pollution by Urticaceae pollen-influence of selected air pollutants and meteorological parameters. AB - The goal of this study was to analyze the influence of pollutants (concentrations of NO2, SO2, and soot in the air) and meteorological parameters (air temperature, humidity, wind speed, air pressure, cloud index) on Urticaceae pollen type emission measured in the region of Subotica, Serbia. The concentrations of the air pollutants, Urticaceae pollen, and meteorological parameters were measured over a 5-year period (2009-2013), followed by a statistical analysis of the values obtained. For most of the years examined, the concentration of NO2 correlates significantly with the concentration of Urticaceae pollen type. It was also established that air temperature, humidity, wind speed, atmospheric pressure, and cloud index have an influence on Urticaceae pollen type emission, while SO2 and soot do not contribute. PMID- 26865494 TI - Health reform in Finland: current proposals and unresolved challenges. AB - The Finnish health care system is widely respected for its pilot role in creating primary-care-led health systems. In the early 1990s, however, a severe economic downturn in Finland reduced public funding and weakened the Finnish system's deeply decentralized model of health care administration. Recent Bank of Finland projections forecasting several decades of slow economic growth, combined with the impact of an aging population, appear to make major reform of the existing public system inevitable. Over the last several years, political attention has focused mostly on administrative consolidation inside the public sector, particularly integration of health and social services. Current proposals call for a reformed health sector governance structure based on a new meso-level configuration of public administration. In addition, Finland's national government has proposed replacing the current multi-channel public funding structure (which includes health insurance subsidies for occupational health services) with a single-channel public funding structure. This commentary examines several key issues involved in reforming the delivery structure of the Finnish health care system. It also explores possible alternative strategies to reform current funding arrangements. The article concludes with a brief discussion of implications from this Finnish experience for the wider health reform debate. PMID- 26865495 TI - Increased Protein Stability and Decreased Protein Turnover in the Caenorhabditis elegans Ins/IGF-1 daf-2 Mutant. AB - In Caenorhabditis elegans, cellular proteostasis is likely essential for longevity. Autophagy has been shown to be essential for lifespan extension of daf 2 insulin/IGF mutants. Therefore, it can be hypothesized that daf-2 mutants achieve this phenotype by increasing protein turnover. However, such a mechanism would exert a substantial energy cost. By using classical 35S pulse-chase labeling, we observed that protein synthesis and degradation rates are decreased in young adults of the daf-2 insulin/IGF mutants. Although reduction of protein turnover may be energetically favorable, it may lead to accumulation and aggregation of damaged proteins. As this has been shown not to be the case in daf 2 mutants, another mechanism must exist to maintain proteostasis in this strain. We observed that proteins isolated from daf-2 mutants are more soluble in acidic conditions due to increased levels of trehalose. This suggests that trehalose may decrease the potential for protein aggregation and increases proteostasis in the daf-2 mutants. We postulate that daf-2 mutants save energy by decreasing protein turnover rates and instead stabilize their proteome by trehalose. PMID- 26865497 TI - Life experiences of caregivers of women with gynaecological cancer: a mixed methods systematic review. AB - Family caregivers play a key role in meeting care needs of cancer patients. The aim of this review was to systematically examine life experiences of family caregivers of women with gynaecological cancer. A mixed-methods systematic review based on a retrospective review of the research on the topic was conducted. The review was limited to articles in English published between 1985 and 2014. The literature search was performed in CINAHL, Scopus, PubMed and ScienceDirect. A total of 16 full-text articles published in national and international journals were reviewed: 10 quantitative studies, 5 qualitative studies and 1 both qualitative and quantitative study. Of all caregivers with gynaecological cancer, 59% were partners, 27% were sons or daughters and 14% were brothers or sisters, mothers and friends. The qualitative research on caregivers' experiences revealed three themes: 'emotional devastation', 'change' and 'coping'. The family caregivers of women with gynaecological cancer had difficulty in areas examined, but the studies investigating caregivers' needs were limited to certain subjects and they were not solution-oriented. It is recommended that qualitative and quantitative studies including the solutions regarding family caregivers of women with gynaecological cancer should be integrated. PMID- 26865498 TI - Suppressed blinking behavior of CdSe/CdS QDs by polymer coating. AB - Semiconductor quantum dots (QDs) are very important fluorescent nanocrystals with excellent optical properties. However, QDs, at the single-particle level, show severe fluorescence intermittency (or blinking) on a wide time scale from milliseconds to minutes, which limits certain optical and biological applications. Generally, blinking behavior of QDs strongly depends on their surface state and surrounding environment. Therefore, current blinking suppression approaches are mostly focused on the introduction of an inorganic shell and organic small molecule compounds. In this study, we described a "bottom up" approach for the synthesis of CdSe/CdS/polymer core/shell/shell QDs via the in situ one-pot polymerization approach in order to control the blinking behavior of QDs. Three monomers (dithiothreitol (DTT), phenylenediamine (PDA), and hexamethylenediamine (HDA)) were respectively used to polymerize with hexachlorocyclotriphosphazene (HCCP), and then the polyphosphazene polymers were obtained with cyclotriphosphazene as the basic macromolecular backbone. By regulating the molar ratios of the activated comonomers, we can control the blinking behavior of CdSe/CdS/polymer QDs. Under the optimal conditions, the percentage of "non-blinking" CdSe/CdS/polymer QDs (the "on time" fraction > 99% of the overall observation time) was up to 78%. The suppression mechanism was attributed to the efficient passivation of QD surface traps by the sulfhydryl or phenyl groups in the polyphosphazene polymers. PMID- 26865496 TI - Antihypertensive Use and the Effect of a Physical Activity Intervention in the Prevention of Major Mobility Disability Among Older Adults: The LIFE Study. AB - BACKGROUND: This subgroup analysis of the Lifestyle Intervention and Independence for Elders trial evaluates the impact of a long-term physical activity (PA) intervention on rates of major mobility disability (MMD) among older adults according to their antihypertensive medication use. METHODS: Lifestyle Intervention and Independence for Elders study participants were randomized to center-based PA or health education for a median of 2.7 years. Participants were sedentary men and women aged 70-89 years with objectively measured physical limitations. This analysis evaluated rates of MMD and persistent MMD among 1,633 participants, according to antihypertensive medication use. Participants were designated as either (i) an angiotensin-converting enzyme (ACE) inhibitor user (ACEi+), (ii) a user of other antihypertensives not including ACEi (ACEi-), or (iii) nonusers of antihypertensive medications (AHT-). Interactions were explored between antihypertensive use and randomized arm. RESULTS: Interaction terms for MMD (p = .214) and persistent MMD (p = .180) did not reach statistical significance. For MMD, PA displayed marginal effects among ACEi+ (hazard ratio [HR] = 0.76; 95% confidence interval [CI] = 0.57, 1.02) and ACEi- (HR = 0.76; 95% CI = 0.60, 0.97) but not AHT- (HR = 1.19; 95% CI = 0.75, 1.87). For persistent MMD, the effect of PA was greatest among ACEi+ (HR = 0.57; 95% CI = 0.39, 0.84) when compared to ACEi- (HR = 0.76; 95% CI = 0.55, 1.06) or AHT- (HR = 1.18; 95% CI = 0.59, 2.36). CONCLUSIONS: The effects of long-term PA on the incidence of MMD and persistent MMD were similar among three subgroups of older adults stratified by their antihypertensive medication use. However, though statistical interactions did not reach significance, several findings may warrant future study in other cohorts given the post hoc nature of this study. PMID- 26865499 TI - Micro-computed tomography analysis of post space preparation in root canals filled with carrier-based thermoplasticized gutta-percha. AB - AIM: To determine whether post space preparation deviated from the root canal preparation in canals filled with Thermafil, GuttaCore or warm vertically compacted gutta-percha. METHODOLOGY: Forty-two extracted human permanent maxillary lateral incisors were decoronated, and their root canals instrumented using a standardized protocol. Samples were divided into three groups and filled with Thermafil (Dentsply Tulsa Dental Specialties, Johnson City, TN, USA), GuttaCore (Dentsply Tulsa Dental Specialties) or warm vertically compacted gutta percha, before post space preparation was performed with a GT Post drill (Dentsply Tulsa Dental Specialties). Teeth were scanned using micro-computed tomography after root filling and again after post space preparation. Scans were examined for number of samples with post space deviation, linear deviation of post space preparation and minimum root thickness before and after post space preparation. Parametric data were analysed with one-way analysis of variance (anova) or one-tailed paired Student's t-tests, whilst nonparametric data were analysed with Fisher's exact test. RESULTS: Deviation occurred in eight of forty two teeth (19%), seven of fourteen from the Thermafil group (50%), one of fourteen from the GuttaCore group (7%), and none from the gutta-percha group. Deviation occurred significantly more often in the Thermafil group than in each of the other two groups (P < 0.05). Linear deviation of post space preparation was greater in the Thermafil group than in both of the other groups and was significantly greater than that of the gutta-percha group (P < 0.05). Minimum root thickness before post space preparation was significantly greater than it was after post space preparation for all groups (P < 0.01). CONCLUSIONS: The differences between the Thermafil, GuttaCore and gutta-percha groups in the number of samples with post space deviation and in linear deviation of post space preparation were associated with the presence or absence of a carrier as well as the different carrier materials. PMID- 26865500 TI - Spin-orbit coupling effects on electronic structures in stanene nanoribbons. AB - The electronic structures and magnetic properties of stanene nanoribbons (SnNRs) were studied using first-principle calculations, considering the spin-orbit coupling (SOC) effects and edge passivation. The results show that all considered armchair SnNRs are nonmagnetic semiconductors with gap values as a periodic oscillation function of ribbon width. The zigzag SnNRs present the antiferromagnetic ground states with opposite spin order between the two edges, and the gaps decrease as the ribbon widths increase. The influences of dangling bonds are obvious on the ferromagnetic moments of zigzag SnNRs. The SOC effects can open the band gap values of stanene sheets and zigzag SnNRs, but reduce the band gap of armchair SnNRs, which indicates that stanene nanostructures may be applied in the fields of spinelectronics and quantum spin Hall. PMID- 26865501 TI - Two GPs face charges of manslaughter over death of boy in 2012. PMID- 26865502 TI - New Twists and Turns for Actinide Chemistry: Organometallic Infinite Coordination Polymers of Thorium Diazide. AB - Two organometallic 1D infinite coordination polymers and two organometallic monometallic complexes of thorium diazide have been synthesized and characterized. Steric control of these self-assembled arrays, which are dense in thorium and nitrogen, has also been demonstrated: infinite chains can be circumvented by using steric bulk either at the metallocene or with a donor ligand in the wedge. PMID- 26865504 TI - Transition metal (Rh and Fe) complexes and main-group (Se and B) adducts with N,N'-diphosphanyl NHC ligands: a study of stereoelectronic properties. AB - Attempts to evaluate experimentally the donor characteristics of the N,N'-bis(di tert-butylphosphanyl)-imidazole-2-ylidene (PC(NHC)P) hybrid ligand are described. Thus, reactions of PC(NHC)P with [Rh(MU-Cl)(COD)]2 and [Rh(MU-Cl)(CO)2]2 led to the formation of the mononuclear and dinuclear complexes, [Rh(PC(NHC)P,kappaP,kappaC(NHC))2]Cl (PC(NHC)P-RhCl) and [Rh(CO)(PC(NHC),kappaP,kappaC(NHC),kappaN)]2 (PC(NHC)-RhCO), respectively, the latter resulting after in situ cleavage of one (t-Bu)2P-Nimid bond of PC(NHC)P. With ligands acting as a P,C-chelate, a straightforward evaluation of the Tolman electronic parameter (TEP) of the C(NHC) donor is problematical; the viability of dangling P- and bound C(NHC)-donors (i.e.kappaC(NHC)) has been observed in the trinuclear Fe(ii) chain complex [Fe3Cl2(MU-Cl)4(THF)2(PC(NHC)P,kappaC(NHC))2] (PC(NHC)P-Fe), obtained by the reaction of PC(NHC)P with [Fe4Cl8(THF)6] and, recently, established on Cr(II), Co(II) and Au(I) centres. Evaluation of the pi accepting properties of the PC(NHC)P (and the related Dipp-PC(NHC)) was based on the (77)Se NMR chemical shifts of the corresponding NHC-Se adducts, PC(NHC)P-Se (and Dipp-PC(NHC)-Se), which were prepared from the free PC(NHC)P (and Dipp PC(NHC)) and Se. The pi-acidity of PC(NHC)P is found to be higher than that of Dipp-PC(NHC) but lower than that of SIPr. The donor ability of the C(NHC) in PC(NHC)P was explored by its reaction with the Lewis acids tris(pentafluorophenyl)borane (B(C6F5)3) and tris(pentafluorophenyl)boroxine ([(C6F5)BO]3), which resulted in stable donor-acceptor adducts with no FLP reactivity. The steric properties of PC(NHC)P and Dipp-PC(NHC) are conformation dependent, with the percent buried volume (%Vbur) of PC(NHC)P in the structurally characterised conformer calculated at 67.6, the largest value currently reported for NHC ligands. PMID- 26865503 TI - Effects of ketanserin on experimental colitis in mice and macrophage function. AB - Ketanserin is a selective 5-hydroxytryptamine (serotonin)-2A receptor (5-HT2AR) antagonist. Studies have suggested that ketanserin exerts anti-inflammatory effects independent of the baroreflex; however, the mechanisms involved remain unclear. Thus, in the present study, we aimed to evaluate the effects of ketanserin in colitis and the possible underlying mechanisms. The expression of 5 HT2AR was assessed in the colon tissues of patients with inflammatory bowel disease (IBD) and in mice with dextran sodium sulfate (DSS)-induced colitis. The therapeutic potential of ketanserin was investigated in the mice with colitis. In the colon tissue samples from the patients with IBD, a high expression level of 5 HT2AR was observed. Treatment with ketanserin attenuated the progression of experimental colitis in the mice, as indicated by body weight assessment, colon length, histological scores and cytokine release. The colonic macrophages from the ketanserin-treated mice with colitis exhibited a decreased production of inflammatory cytokines, with M2 polarization and impaired migration. The knockdown of 5-HT2AR using siRNA partly abolished the inhibitory effects of ketanserin on the release of pro-inflammatory cytokines in bone marrow derived macrophages (BMDMs), thus demonstrating that the inhibitory effects of ketanserin on the production of inflammatory cytokines are partly dependent on 5-HT2AR. Ketanserin also inhibited the activation of nuclear factor-kappaB (NF-kappaB) in BMDMs. In conclusion, the findings of the present study demonstrate that ketanserin alleviates colitis. Its anti-inflammatory effects may be due to the promotion of the anti-inflammatory function of macrophages through 5-HT2AR/NF kappaB. PMID- 26865507 TI - 1D/2D Carbon Nanomaterial-Polymer Dielectric Composites with High Permittivity for Power Energy Storage Applications. AB - With the development of flexible electronic devices and large-scale energy storage technologies, functional polymer-matrix nanocomposites with high permittivity (high-k) are attracting more attention due to their ease of processing, flexibility, and low cost. The percolation effect is often used to explain the high-k characteristic of polymer composites when the conducting functional fillers are dispersed into polymers, which gives the polymer composite excellent flexibility due to the very low loading of fillers. Carbon nanotubes (CNTs) and graphene nanosheets (GNs), as one-dimensional (1D) and two-dimensional (2D) carbon nanomaterials respectively, have great potential for realizing flexible high-k dielectric nanocomposites. They are becoming more attractive for many fields, owing to their unique and excellent advantages. The progress in dielectric fields by using 1D/2D carbon nanomaterials as functional fillers in polymer composites is introduced, and the methods and mechanisms for improving dielectric properties, breakdown strength and energy storage density of their dielectric nanocomposites are examined. Achieving a uniform dispersion state of carbon nanomaterials and preventing the development of conductive networks in their polymer composites are the two main issues that still need to be solved in dielectric fields for power energy storage. Recent findings, current problems, and future perspectives are summarized. PMID- 26865506 TI - Pectic polysaccharides are attacked by hydroxyl radicals in ripening fruit: evidence from a fluorescent fingerprinting method. AB - BACKGROUND AND AIMS: Many fruits soften during ripening, which is important commercially and in rendering the fruit attractive to seed-dispersing animals. Cell-wall polysaccharide hydrolases may contribute to softening, but sometimes appear to be absent. An alternative hypothesis is that hydroxyl radicals ((*)OH) non-enzymically cleave wall polysaccharides. We evaluated this hypothesis by using a new fluorescent labelling procedure to 'fingerprint' (*)OH-attacked polysaccharides. METHODS: We tagged fruit polysaccharides with 2-(isopropylamino) acridone (pAMAC) groups to detect (a) any mid-chain glycosulose residues formed in vivo during (*)OH action and (b) the conventional reducing termini. The pAMAC labelled pectins were digested with Driselase, and the products resolved by high voltage electrophoresis and high-pressure liquid chromatography. KEY RESULTS: Strawberry, pear, mango, banana, apple, avocado, Arbutus unedo, plum and nectarine pectins all yielded several pAMAC-labelled products. GalA-pAMAC (monomeric galacturonate, labelled with pAMAC at carbon-1) was produced in all species, usually increasing during fruit softening. The six true fruits also gave pAMAC.UA-GalA disaccharides (where pAMAC.UA is an unspecified uronate, labelled at a position other than carbon-1), with yields increasing during softening. Among false fruits, apple and strawberry gave little pAMAC.UA-GalA; pear produced it transiently. CONCLUSIONS: GalA-pAMAC arises from pectic reducing termini, formed by any of three proposed chain-cleaving agents ((*)OH, endopolygalacturonase and pectate lyase), any of which could cause its ripening related increase. In contrast, pAMAC.UA-GalA conjugates are diagnostic of mid chain oxidation of pectins by (*)OH. The evidence shows that (*)OH radicals do indeed attack fruit cell wall polysaccharides non-enzymically during softening in vivo. This applies much more prominently to drupes and berries (true fruits) than to false fruits (swollen receptacles). (*)OH radical attack on polysaccharides is thus predominantly a feature of ovary-wall tissue. PMID- 26865505 TI - Intrinsic and membrane-facilitated alpha-synuclein oligomerization revealed by label-free detection through solid-state nanopores. AB - alpha-Synuclein (alpha-Syn) is an abundant cytosolic protein involved in the release of neurotransmitters in presynaptic terminal and its aberrant aggregation is found to be associated with Parkinson's disease. Recent study suggests that the oligomers formed at the initial oligomerization stage may be the root cause of cytotoxicity. While characterizing this stage is challenging due to the inherent difficulties in studying heterogeneous and transient systems by conventional biochemical technology. Here we use solid-state nanopores to study the time-dependent kinetics of alpha-Syn oligomerization through a label-free and single molecule approach. A tween 20 coating method is developed to inhibit non specific adsorption between alpha-Syn and nanopore surface to ensure successful and continuous detection of alpha-Syn translocation. We identify four types of oligomers formed in oligomerization stage and find an underlying consumption mechanism that the formation of large oligomers consumes small oligomers. Furthermore, the effect of lipid membrane on oligomerization of alpha-Syn is also investigated and the results show that 1,2-dioleoyl-sn-glycero-3-[phospho-L serine] (DOPS) small unilamellar vesicles (SUVs) dramatically enhances the aggregation rate of alpha-Syn while do not alter the aggregation pathway. PMID- 26865508 TI - Lung function gain in preterm infants with and without bronchopulmonary dysplasia. AB - OBJECTIVES: The aim of our study was to determine whether the development of lung function, during the first 2 years of life, is different in preterm infants who suffered or did not suffer from Bronchopulmonary dysplasia (BPD). We also assessed the role of nutritional status and growth in that development. METHODS: Lung function tests were performed in 71 preterm infants at two time points: 6 months of corrected age and 1 year after. FVC, FEV0.5, FEF75 , and FEF25-75 were obtained from maximal expiratory volume curves by means of the raised volume rapid thoraco-abdominal compression technique. RESULTS: When comparing lung function measurements, we found that FVC (P = 0.033) FEV0.5 (P = 0.044), FEF75 (P = 0.014), and FEF25-75 (P = 0.036) were significantly lower in BPD infants. We did not find any catch-up of lung function during the study time, in neither the whole group of children nor within the BPD or non-BPD groups. The increase in lung function was directly proportional to the increase in weight and length. The multivariate analysis showed that the increase in z-score of FVC (P = 0.043), FEV0.5 (P = 0.015), and FEF75 (P = 0.042), was related with the height velocity during the study period. CONCLUSIONS: Infants who suffered from BPD have lower lung function (FVC, FEV0.5 , FEF75 , and FEF25-75 ), than those non-BPD, at two different time points 1 year apart. During the study period, there was no lung function catch-up in either BPD or non-BPD infants. The increase in length is closely associated to the increase in lung function. Pediatr Pulmonol. 2016; 51:936-942. (c) 2016 Wiley Periodicals, Inc. PMID- 26865509 TI - Dihydroartemisinin prevents liver fibrosis in bile duct ligated rats by inducing hepatic stellate cell apoptosis through modulating the PI3K/Akt pathway. AB - As a frequent event following chronic insult, liver fibrosis triggers wound healing reactions, with extracellular matrix components accumulated in the liver. During liver fibrogenesis, activation of hepatic stellate cells (HSCs) is the pivotal event. Fibrosis regression can feasibly be treated through pharmacological induction of HSC apoptosis. Herein we showed that dihydroartemisinin (DHA) improved liver histological architecture, decreased hepatic enzyme levels, and inhibited HSCs activation in the fibrotic rat liver. DHA also induced apoptosis of HSCs in such liver, as demonstrated by reduced distribution of alpha-SMA-positive cells and the presence of high number of cleaved-caspase-3-positive cells in vivo, as well as by down-regulation of Bcl-2 and up-regulation of Bax. In addition, in vitro experiments showed that DHA significantly inhibited HSC proliferation and led to dramatic morphological alterations in HSCs. we found that DHA disrupted mitochondrial functions and led to activation of caspase cascades in HSCs. Mechanistic investigations revealed that DHA induced HSC apoptosis through disrupting the phosphoinositide 3-kinase (PI3K)/Akt pathway and that PI3K specific inhibitor LY294002 mimicked the pro apoptotic effect of DHA. DHA is a promising candidate for the prevention and treatment of liver fibrosis. PMID- 26865510 TI - Pre-pregnancy maternal obesity and the risk of preterm preeclampsia in the American primigravida. AB - OBJECTIVE: To estimate the risk of preterm preeclampsia in primiparous women by pre-pregnancy obesity class. METHODS: A retrospective cohort study of primiparous women with singleton gestations was performed for deliveries from January 2003 to April 2014. Cases were stratified by delivery occurring either at >= 37 weeks or < 37 weeks. Pre-pregnancy maternal obesity was defined as a body mass index (BMI) >= 30 kg/m(2) . World Health Organization criteria were used to define BMI class of obesity. Multinomial logistic regression modeling estimated the association between term and preterm preeclampsia and pre-pregnancy obesity. RESULTS: Of 28,361 women with complete pre-pregnancy BMI data, 2,588 women (9.1%) had a diagnosis of preeclampsia. Women who developed preeclampsia prior to 37 weeks (n = 784) were more likely to be women with obesity compared to women who developed preeclampsia after 37 weeks (33.1% vs. 25.3%, P = 0.0001). Compared to normal weight women without preeclampsia, the risk of preterm preeclampsia increased proportionally with pre-pregnancy obesity class, with women with a BMI >= 40 kg/m(2) having the greatest risk (RR 5.23, 95% CI: 3.86-7.09, P <0.001). CONCLUSIONS: The risk of preterm preeclampsia increased significantly as the severity of maternal pre-pregnancy obesity increased. Reduction in maternal pre pregnancy BMI may be protective in mitigating such risk. PMID- 26865511 TI - Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. AB - OBJECTIVE: To examine safety, tolerability, pharmacokinetics, and preliminary clinical efficacy of intrathecal nusinersen (previously ISIS-SMNRx), an antisense oligonucleotide designed to alter splicing of SMN2 mRNA, in patients with childhood spinal muscular atrophy (SMA). METHODS: Nusinersen was delivered by intrathecal injection to medically stable patients with type 2 and type 3 SMA aged 2-14 years in an open-label phase 1 study and its long-term extension. Four ascending single-dose levels (1, 3, 6, and 9 mg) were examined in cohorts of 6-10 participants. Participants were monitored for safety and tolerability, and CSF and plasma pharmacokinetics were measured. Exploratory efficacy endpoints included the Hammersmith Functional Motor Scale Expanded (HFMSE) and Pediatric Quality of Life Inventory. RESULTS: A total of 28 participants enrolled in the study (n = 6 in first 3 dose cohorts; n = 10 in the 9-mg cohort). Intrathecal nusinersen was well-tolerated with no safety/tolerability concerns identified. Plasma and CSF drug levels were dose-dependent, consistent with preclinical data. Extended pharmacokinetics indicated a prolonged CSF drug half-life of 4-6 months after initial clearance. A significant increase in HFMSE scores was observed at the 9-mg dose at 3 months postdose (3.1 points; p = 0.016), which was further increased 9-14 months postdose (5.8 points; p = 0.008) during the extension study. CONCLUSIONS: Results from this study support continued development of nusinersen for treatment of SMA. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SMA, intrathecal nusinersen is not associated with safety or tolerability concerns. PMID- 26865512 TI - Urinary LRRK2 phosphorylation predicts parkinsonian phenotypes in G2019S LRRK2 carriers. AB - OBJECTIVE: To test whether phosphorylated Ser-1292 LRRK2 levels in urine exosomes predicts LRRK2 mutation carriers (LRRK2+) and noncarriers (LRRK2-) with Parkinson disease (PD+) and without Parkinson disease (PD-). METHODS: LRRK2 protein was purified from urinary exosomes collected from participants in 2 independent cohorts. The first cohort included 14 men (LRRK2+/PD+, n = 7; LRRK2-/PD+, n = 4; LRRK2-/PD-, n = 3). The second cohort included 62 men (LRRK2-/PD-, n = 16; LRRK2+/PD-, n = 16; LRRK2+/PD+, n = 14; LRRK2-/PD+, n = 16). The ratio of Ser(P) 1292 LRRK2 to total LRRK2 was compared between LRRK2+/PD+ and LRRK2- in the first cohort and between LRRK2 G2019S carriers with and without PD in the second cohort. RESULTS: LRRK2+/PD+ had higher ratios of Ser(P)-1292 LRRK2 to total LRRK2 than LRRK2-/PD- (4.8-fold, p < 0.001) and LRRK2-/PD+ (4.6-fold, p < 0.001). Among mutation carriers, those with PD had higher Ser(P)-1292 LRRK2 to total LRRK2 than those without PD (2.2-fold, p < 0.001). Ser(P)-1292 LRRK2 levels predicted symptomatic from asymptomatic carriers with an area under the receiver operating characteristic curve of 0.844. CONCLUSION: Elevated ratio of phosphorylated Ser 1292 LRRK2 to total LRRK2 in urine exosomes predicted LRRK2 mutation status and PD risk among LRRK2 mutation carriers. Future studies may explore whether interventions that reduce this ratio may also reduce PD risk. PMID- 26865513 TI - STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy. AB - OBJECTIVE: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients. METHODS: We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients. RESULTS: We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features. CONCLUSION: De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy. PMID- 26865515 TI - Biomarkers for the progression of Parkinson disease. PMID- 26865514 TI - Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. AB - OBJECTIVE: To determine the short-term and long-term effects of dichlorphenamide (DCP) on attack frequency and quality of life in hyperkalemic (HYP) and hypokalemic (HOP) periodic paralysis. METHODS: Two multicenter randomized, double blind, placebo-controlled trials lasted 9 weeks (Class I evidence), followed by a 1-year extension phase in which all participants received DCP. Forty-four HOP and 21 HYP participants participated. The primary outcome variable was the average number of attacks per week over the final 8 weeks of the double-blind phase. RESULTS: The median attack rate was lower in HOP participants on DCP than in participants on placebo (0.3 vs 2.4, p = 0.02). The 9-week mean change in the Physical Component Summary score of the Short Form-36 was also better in HOP participants receiving DCP (treatment effect = 7.29 points, 95% confidence interval 2.26 to 12.32, p = 0.006). The median attack rate was also lower in HYP participants on DCP (0.9 vs 4.8) than in participants on placebo, but the difference in median attack rate was not significant (p = 0.10). There were no significant effects of DCP on muscle strength or muscle mass in either trial. The most common adverse events in both trials were paresthesia (47% DCP vs 14% placebo, both trials combined) and confusion (19% DCP vs 7% placebo, both trials combined). CONCLUSIONS: DCP is effective in reducing the attack frequency, is safe, and improves quality of life in HOP periodic paralysis. CLASSIFICATION OF EVIDENCE: These studies provide Class I evidence that DCP significantly reduces attack frequency in HOP but lacked the precision to support either efficacy or lack of efficacy of DCP in HYP. PMID- 26865520 TI - Urinary LRRK2 phosphorylation: Penetrating the thicket of Parkinson disease? PMID- 26865519 TI - Midlife exercise blood pressure, heart rate, and fitness relate to brain volume 2 decades later. AB - OBJECTIVE: To determine whether poor cardiovascular (CV) fitness and exaggerated exercise blood pressure (BP) and heart rate (HR) were associated with worse brain morphology in later life. METHODS: Framingham Offspring participants (n = 1,094, 53.9% female) free from dementia and CV disease (CVD) underwent an exercise treadmill test at a mean age of 40 +/- 9 years. A second treadmill test and MRI scans of the brain were administered 2 decades later at mean age of 58 +/- 8 years. RESULTS: Poor CV fitness and greater diastolic BP and HR response to exercise at baseline were associated with a smaller total cerebral brain volume (TCBV) almost 2 decades later (all p < 0.05) in multivariable adjusted models; the effect of 1 SD lower fitness was equivalent to approximately 1 additional year of brain aging in individuals free of CVD. In participants with prehypertension or hypertension at baseline, exercise systolic BP was also associated with smaller TCBV (p < 0.05). CONCLUSION: Our results suggest that lower CV fitness and exaggerated exercise BP and HR responses in middle-aged adults are associated with smaller brain volume nearly 2 decades later. Promotion of midlife CV fitness may be an important step towards ensuring healthy brain aging. PMID- 26865518 TI - Age at onset and Parkinson disease phenotype. AB - OBJECTIVE: To explore clinical phenotype and characteristics of Parkinson disease (PD) at different ages at onset in recently diagnosed patients with untreated PD. METHODS: We have analyzed baseline data from the Parkinson's Progression Markers Initiative database. Four hundred twenty-two patients with a diagnosis of PD confirmed by DaTSCAN imaging were divided into 4 groups according to age at onset (onset younger than 50 years, 50-59 years, 60-69 years, and 70 years or older) and investigated for differences in side, type and localization of symptoms, occurrence/severity of motor and nonmotor features, nigrostriatal function, and CSF biomarkers. RESULTS: Older age at onset was associated with a more severe motor and nonmotor phenotype, a greater dopaminergic dysfunction on DaTSCAN, and reduction of CSF alpha-synuclein and total tau. The most common presentation was the combination of 2 or 3 motor symptoms (bradykinesia, resting tremor, and rigidity) with rigidity being more common in the young-onset group. In about 80% of the patients with localized onset, the arm was the most affected part of the body, with no difference across subgroups. CONCLUSIONS: Although the presentation of PD symptoms is similar across age subgroups, the severity of motor and nonmotor features, the impairment of striatal binding, and the levels of CSF biomarkers increase with age at onset. The variability of imaging and nonimaging biomarkers in patients with PD at different ages could hamper the results of future clinical trials. PMID- 26865521 TI - Spinal muscular atrophy: A preliminary result toward new therapy. PMID- 26865522 TI - A newly approved drug for a rare group of diseases: Dichlorphenamide for periodic paralysis. PMID- 26865517 TI - Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study. AB - OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563). METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg. RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score <=2.5; probability of 12-week disability progression <=0.48). CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well tolerated and efficacy of teriflunomide is maintained long-term. PMID- 26865516 TI - Standardized EEG interpretation accurately predicts prognosis after cardiac arrest. AB - OBJECTIVE: To identify reliable predictors of outcome in comatose patients after cardiac arrest using a single routine EEG and standardized interpretation according to the terminology proposed by the American Clinical Neurophysiology Society. METHODS: In this cohort study, 4 EEG specialists, blinded to outcome, evaluated prospectively recorded EEGs in the Target Temperature Management trial (TTM trial) that randomized patients to 33 degrees C vs 36 degrees C. Routine EEG was performed in patients still comatose after rewarming. EEGs were classified into highly malignant (suppression, suppression with periodic discharges, burst suppression), malignant (periodic or rhythmic patterns, pathological or nonreactive background), and benign EEG (absence of malignant features). Poor outcome was defined as best Cerebral Performance Category score 3-5 until 180 days. RESULTS: Eight TTM sites randomized 202 patients. EEGs were recorded in 103 patients at a median 77 hours after cardiac arrest; 37% had a highly malignant EEG and all had a poor outcome (specificity 100%, sensitivity 50%). Any malignant EEG feature had a low specificity to predict poor prognosis (48%) but if 2 malignant EEG features were present specificity increased to 96% (p < 0.001). Specificity and sensitivity were not significantly affected by targeted temperature or sedation. A benign EEG was found in 1% of the patients with a poor outcome. CONCLUSIONS: Highly malignant EEG after rewarming reliably predicted poor outcome in half of patients without false predictions. An isolated finding of a single malignant feature did not predict poor outcome whereas a benign EEG was highly predictive of a good outcome. PMID- 26865525 TI - EEG and cardiac arrest: Divining prognosis at the bedside. PMID- 26865524 TI - Holmes tremor: Clinical description, lesion localization, and treatment in a series of 29 cases. AB - OBJECTIVE: To describe the clinical features, etiology, findings from neuroimaging, and treatment results in a series of 29 patients with Holmes tremor (HT). METHODS: A retrospective study was performed based on review of medical records and videos of patients with HT diagnosis. RESULTS: A total of 16 women and 13 men were included. The mean age at the moment of CNS insult was 33.9 +/- 20.1 years (range 8-76 years). The most common causes were vascular (48.3%), ischemic, or hemorrhagic. Traumatic brain injury only represented 17.24%; other causes represented 34.5%. The median latency from lesion to tremor onset was 2 months (range 7 days-228 months). The most common symptoms/signs associated with HT were hemiparesis (62%), ataxia (51.7%), hypoesthesia (27.58%), dystonia (24.1%), cranial nerve involvement (24.1%), and dysarthria (24.1%). Other symptoms/signs were vertical gaze disorders (6.8%), bradykinesia/rigidity (6.8%), myoclonus (3.4%), and seizures (3.4%). Most of the patients had lesions involving more than one area. MRI showed lesions in thalamus or midbrain or cerebellum in 82.7% of the patients. Levodopa treatment was effective in 13 out of 24 treated patients (54.16%) and in 3 patients unilateral thalamotomy provided excellent results. CONCLUSIONS: The most common causes of HT in our series were vascular lesions. The most common lesion topography was mesencephalic, thalamic, or both. Treatment with levodopa and thalamic stereotactic lesional surgery seems to be effective. PMID- 26865523 TI - Recommendations for observational studies of comorbidity in multiple sclerosis. AB - OBJECTIVE: To reach consensus about the most relevant comorbidities to study in multiple sclerosis (MS) with respect to incidence, prevalence, and effect on outcomes; review datasets that may support studies of comorbidity in MS; and identify MS outcomes that should be prioritized in such studies. METHODS: We held an international workshop to meet these objectives, informed by a systematic review of the incidence and prevalence of comorbidity in MS, and an international survey regarding research priorities for comorbidity. RESULTS: We recommend establishing age- and sex-specific incidence and prevalence estimates for 5 comorbidities (depression, anxiety, hypertension, hyperlipidemia, and diabetes); evaluating the effect of 7 comorbidities (depression, anxiety, hypertension, diabetes, hyperlipidemia, chronic lung disease, and autoimmune diseases) on disability, quality of life, brain atrophy and other imaging parameters, health care utilization, employment, and mortality, including age, sex, race/ethnicity, socioeconomic status, and disease duration as potential confounders; harmonizing study designs across jurisdictions; and conducting such studies worldwide. Ultimately, clinical trials of treating comorbidity in MS are needed. CONCLUSION: Our recommendations will help address knowledge gaps regarding the incidence, prevalence, and effect of comorbidity on outcomes in MS. PMID- 26865527 TI - Concurrent Hypoparathyroidism Is Associated With Impaired Physical Function and Quality of Life in Hypothyroidism. AB - Total thyroidectomy causes postsurgical hypothyroidism (HypoT). Besides HypoT, as a complication patients may also develop hypoparathyroidism (HypoPT). The aim of this study was to assess quality of life (QoL), muscle function, and postural stability in patients with postsurgical hypothyroidism and hypoparathyroidism (HypoT+PT) as compared to patients with postsurgical HypoT and healthy controls. Age- and gender-matched patients on treatment for HypoT+PT and HypoT were recruited from our outpatient clinic. Matched healthy controls were recruited from the general background population. Compared with controls, HypoT was associated with a significantly lower mental summary score, whereas patients with HypoT+PT had a significantly lower physical summary score (Short Form 36 Health Survey questionnaire version 2). Moreover, the physical component score was significantly lower in patients with HypoT+PT compared with HypoT. WHO-5 well being index was significantly lower in both groups of patients compared with controls, but did not differ between groups of patients. Compared with controls, muscle strength and maximal force production was significantly reduced in HypoT+PT, but not in HypoT. In HypoT+PT, the time spent on the Timed Up & Go test and the Repeated Chair Stands test were significantly longer than in the HypoT group and the control group. Postsurgical HypoT+PT is associated with a more severe impairment of QoL, in particular regarding physical functioning, than HypoT. HypoT+PT patients are also hampered by impaired muscle function. Studies on how to improve well-being and muscle function in HypoT+PT patients are warranted. (c) 2016 American Society for Bone and Mineral Research. PMID- 26865526 TI - Rapid Urine LAM Testing Improves Diagnosis of Expectorated Smear-Negative Pulmonary Tuberculosis in an HIV-endemic Region. AB - We sought to determine if urine lipoarabinomannan (LAM) would improve diagnosis of pulmonary TB. We enrolled consecutive adults presenting with >=2 TB-related symptoms, obtained one induced sputum sample for smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing (Determine(TM) TB LAM, Alere). We used culture-confirmed pulmonary TB as the gold standard, and compared accuracy with area under receiver operating characteristic curves (AUROC). Among 90 participants, 82 of 88 tested (93%) were HIV-infected with a median CD4 168/mm(3) (IQR 89-256/mm(3)). Diagnostic sensitivities of urine LAM and sputum AFB were 42.1% (95% CI 29.1-55.9%) and 21.1% (95% CI 11.4-33.9%), and increased to 52.6% (95% CI 39.0-66.0%) when combined. Sensitivity of LAM increased significantly among participants with a lower Karnofsky Performance score, anemia, hypoalbuminemia, and higher C-reactive protein. Combining LAM with AFB had an AUROC = 0.68 (95% CI 0.59-0.77), significantly better than AFB alone (AUROC=0.58; 95% CI 0.51-0.64). The combination of LAM and AFB was significantly better than AFB alone among patients with Karnofsky Performance score <=90, hemoglobin <=10 g/dL, albumin <=25 g/L, C-reactive protein >=25 mg/L, or CD4 <200/mm(3). Urine LAM testing may be most beneficial among patients with functional impairment, elevated inflammatory markers, or greater immunosuppression. PMID- 26865529 TI - Blind sac closure: a safe and effective management option for the chronically discharging ear. PMID- 26865528 TI - Evolution of short inverted repeat in cupressophytes, transfer of accD to nucleus in Sciadopitys verticillata and phylogenetic position of Sciadopityaceae. AB - Sciadopitys verticillata is an evergreen conifer and an economically valuable tree used in construction, which is the only member of the family Sciadopityaceae. Acquisition of the S. verticillata chloroplast (cp) genome will be useful for understanding the evolutionary mechanism of conifers and phylogenetic relationships among gymnosperm. In this study, we have first reported the complete chloroplast genome of S. verticillata. The total genome is 138,284 bp in length, consisting of 118 unique genes. The S. verticillata cp genome has lost one copy of the canonical inverted repeats and shown distinctive genomic structure comparing with other cupressophytes. Fifty-three simple sequence repeat loci and 18 forward tandem repeats were identified in the S. verticillata cp genome. According to the rearrangement of cupressophyte cp genome, we proposed one mechanism for the formation of inverted repeat: tandem repeat occured first, then rearrangement divided the tandem repeat into inverted repeats located at different regions. Phylogenetic estimates inferred from 59 gene sequences and cpDNA organizations have both shown that S. verticillata was sister to the clade consisting of Cupressaceae, Taxaceae, and Cephalotaxaceae. Moreover, accD gene was found to be lost in the S. verticillata cp genome, and a nucleus copy was identified from two transcriptome data. PMID- 26865531 TI - Reduction of hip joint reaction force via medio-lateral foot center of pressure manipulation in bilateral hip osteoarthritis patients. AB - Loading/excessive loading of the hip joint has been linked to onset and progression of hip osteoarthritis. Footwear-generated biomechanical manipulation in the frontal plane has been previously shown in a cohort of healthy subjects to cause a specific gait adaption when the foot center of pressure trajectory was shifted medially, which thereby significantly reduced hip joint reaction force. The objective of the present study was to validate these results in a cohort of female bilateral hip osteoarthritis patients. Sixteen patients underwent gait analysis while using a footworn biomechanical device, allowing controlled foot center of pressure manipulation, in three para-sagittal configurations: medial, lateral, and neutral. Hip osteoarthritis patients exhibited similar results to those observed in healthy subjects in that a medial center of pressure led to an increase in inter-maleolar distance while step width (i.e., distance between right and left foot center of pressure) remained constant. This adaptation, which we speculate subjects adopt to maintain base of support, was associated with significantly greater hip abduction, significantly decreased hip adduction moment, and significantly reduced joint reaction force compared to the neutral and lateral configurations. Recommendations for treatment of hip osteoarthritis emphasize reduction of loads on the pathological joint(s) during daily activities and especially in gait. Our results show that a medially deviated center of pressure causes a reduction in hip joint reaction force. The present study does not prove, but rather suggests, clinical significance, and further investigation is required to assess clinical implications. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1762-1771, 2016. PMID- 26865530 TI - Wound-healing factors can prime head and neck cancer cells to increase their tumor-forming capacity. AB - OBJECTIVES/HYPOTHESIS: We investigated whether exposing a wound-healing-sensitive cell line to human wound fluid (HWF) could prime the cells to increase their tumor-forming ability in nude mice and, if so, whether this ability can be inhibited by pharmacological substances. STUDY DESIGN: Experimental animal model. METHODS: Take rate was measured in BALB/c nude mice after pretreatment of the cells with HWF using human serum and fetal bovine serum as controls. Inhibition of signal transducer and activator of transcription 3 (STAT3) with S3I-201 tocilizumab, and of interleukin 6 receptor (IL6R) with tocilizumab was performed. RESULTS: Preincubation with HWF resulted in a significant increase in take rate compared to controls. The increase in take rate could be decreased by both STAT3 and IL6R inhibition. CONCLUSIONS: The results indicate that head and neck squamous cell cancer cells might be stimulated to increase their tumor-forming ability both close to a surgical wound and at more distant locations, as a consequence of the wound-healing response. The work also suggests new treatment modalities aimed at decreasing these stimulatory effects. LEVEL OF EVIDENCE: NA Laryngoscope, 126:E213-E217, 2016. PMID- 26865532 TI - Mammalian Autophagy: How Does It Work? AB - Autophagy is a conserved intracellular pathway that delivers cytoplasmic contents to lysosomes for degradation via double-membrane autophagosomes. Autophagy substrates include organelles such as mitochondria, aggregate-prone proteins that cause neurodegeneration and various pathogens. Thus, this pathway appears to be relevant to the pathogenesis of diverse diseases, and its modulation may have therapeutic value. Here, we focus on the cell and molecular biology of mammalian autophagy and review the key proteins that regulate the process by discussing their roles and how these may be modulated by posttranslational modifications. We consider the membrane-trafficking events that impact autophagy and the questions relating to the sources of autophagosome membrane(s). Finally, we discuss data from structural studies and some of the insights these have provided. PMID- 26865533 TI - Necroptosis and Inflammation. AB - Necroptosis is a regulated form of necrosis, with the dying cell rupturing and releasing intracellular components that can trigger an innate immune response. Toll-like receptor 3 and 4 agonists, tumor necrosis factor, certain viral infections, or the T cell receptor can trigger necroptosis if the activity of the protease caspase-8 is compromised. Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. Either RIPK3 deficiency or RIPK1 inhibition confers resistance in various animal disease models, suggesting that inflammation caused by necroptosis contributes to tissue damage and that inhibitors of these kinases could have therapeutic potential. Recent studies have revealed unexpected complexity in the regulation of cell death programs by RIPK1 and RIPK3 with the possibility that necroptosis is but one mechanism by which these kinases promote inflammation. PMID- 26865535 TI - Comparison of alogliptin and glipizide for composite endpoint of glycated haemoglobin reduction, no hypoglycaemia and no weight gain in type 2 diabetes mellitus. AB - This was a post hoc analysis of a 2-year, double-blind study of 2639 patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin monotherapy, which assessed achievement of a composite endpoint of sustained glycated haemoglobin (HbA1c) reduction (<=7.0% at week 104 or >=0.5% decrease from baseline) with no weight gain and no hypoglycaemic events with alogliptin 12.5 and 25 mg daily or glipizide (<=20 mg daily), each added to metformin. With an HbA1c target of <=7.0%, 24.2 and 26.9% of patients treated with alogliptin 12.5 and 25 mg, respectively, achieved the composite endpoint versus 10.7% of patients treated with glipizide (both p < 0.001). With a criterion of >=0.5% decrease in HbA1c, the composite endpoint was reached in 22.5, 25.2 and 10.4% of patients treated with alogliptin 12.5 mg, alogliptin 25 mg and glipizide, respectively. Odds ratios for achieving the composite endpoint favoured alogliptin in the primary analysis set and in all subgroups of patients. Patients with T2DM failing metformin monotherapy were more likely to achieve sustained glycaemic control with no hypoglycaemia or weight gain at 2 years with alogliptin than with glipizide. PMID- 26865536 TI - Differences between diploma and baccalaureate dental hygiene education in British Columbia: a qualitative perspective. AB - : The British Columbia Ministry of Health in Canada approved a new registration category for dental hygienists in 2012. This category included four abilities that registrants were required to demonstrate at a 4th-year baccalaureate degree level. OBJECTIVE: To identify the differences, if any, between diploma and bachelor's degree education with regard to the 4 legislated abilities focused on the process of care for clients with complex needs and/or disabling conditions including client safety, referrals and interprofessional collaboration. METHODS: Registrants who had entered practice with a diploma and then gained a baccalaureate degree were invited to participate in an online survey including closed- and open-ended questions. The study was a mixed-method design where the qualitative data were nested concurrently in the open-ended questions; the data were analysed through thematic analysis using grounded theory methods. RESULTS AND DISCUSSION: Respondents (n = 123; 51%) indicated their client care had improved with baccalaureate education due to increased knowledge, increased understanding and increased abilities to make judgements with a particular emphasis on evidence-based decisions. These more advanced abilities provided them with increased confidence for taking action particularly in interprofessional contexts and increased the quality of their decision-making thus leading to better care for clients. CONCLUSION: Respondents described their dental hygiene services as generally being of a higher standard and specifically in the 4 legislated abilities as a direct result of baccalaureate education. PMID- 26865538 TI - Physiological responses during exposure to carbon dioxide and bioeffluents at levels typically occurring indoors. AB - Twenty-five subjects were exposed to different levels of carbon dioxide (CO2 ) and bioeffluents. The ventilation rate was set high enough to create a reference condition of 500 ppm CO2 with subjects present; additional CO2 was then added to supply air to reach levels of 1000 or 3000 ppm, or the ventilation rate was reduced to allow metabolically generated CO2 to reach the same two levels (bioeffluents increased as well). Heart rate, blood pressure, end-tidal CO2 (ETCO2 ), oxygen saturation of blood (SPO2 ), respiration rate, nasal peak flow, and forced expiration were monitored, and the levels of salivary alpha-amylase and cortisol were analyzed. The subjects performed a number of mental tasks during exposures and assessed their levels of comfort and the intensity of their acute health symptoms. During exposure to CO2 at 3000 ppm, when CO2 was added or ventilation was restricted, ETCO2 increased more and heart rate decreased less than the changes that occurred in the reference condition. Exposure to bioeffluents, when metabolically generated CO2 was at 3000 ppm, significantly increased diastolic blood pressure and salivary alpha-amylase level compared with pre-exposure levels, and reduced the performance of a cue-utilization test: These effects may suggest higher arousal/stress. A model is proposed describing how mental performance is affected by exposure to bioeffluents. PMID- 26865537 TI - Patterns of regional and distant metastasis in esthesioneuroblastoma. AB - OBJECTIVES/HYPOTHESIS: To define the incidence and risk factors of metastatic disease and the effectiveness of salvage therapy in esthesioneuroblastoma (ENB). STUDY DESIGN: Retrospective analysis of 57 patients presenting from 1979 through 2009. METHODS: Cumulative incidence of neck failure, distant failure, and survival were assessed using the Kaplan-Meier method. RESULTS: Overall survival for all patients was 85% at 5 years and 75% at 10 years. Overall survival was negatively impacted by intracranial tumor extension (P < 0.001), positive resection margins (P = 0.05), and neck metastases (P = 0.017). Neck lymph nodes were not routinely electively irradiated during this time period. Nodal metastases developed in 17% of patients at a median time of 60 months. Kadish stage was not associated with a risk of nodal metastasis (P = 0.78). After treatment for nodal recurrence, locoregional control was achieved in 78% of patients. Of patients developing nodal recurrence, more than half developed distant metastases. The cumulative incidence of distant metastasis was 39% at a median time of 40 months. Patients who presented with Kadish stage C or D had a significantly increased risk of distant failure (P < 0.001). In patients developing nodal (P = 0.017) or distant metastasis (P = 0.001), the probability of survival was significantly decreased. CONCLUSION: Regional and distant metastases in patients with esthesioneuroblastoma occur in a delayed fashion and negatively impact survival. Neck nodal recurrence may be a harbinger of distant metastases. At the Memorial Sloan Kettering Cancer Center, New York, New York, we now treat the majority of ENB patients with elective nodal irradiation. However, the chief obstacle to long-term cure is distant metastases. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1556-1561, 2016. PMID- 26865539 TI - Effect of perceived organizational support on suicidal ideation of young employees: The mediator role of self-esteem. AB - This study aimed to explore the relationships among perceived organizational support, self-esteem, and suicidal ideation of young employees. A total of 447 unmarried employees completed the survey of perceived organizational support, Rosenberg self-esteem scale, and suicide ideation scale. The results revealed that perceived organizational support, self-esteem, and suicidal ideation were significantly correlated with each other. Stepwise regression analysis and path analysis both indicated that self-esteem partially mediated the effect of perceived organizational support on suicidal ideation. PMID- 26865540 TI - When seconds count: A study of communication variables in the opening segment of emergency calls. AB - The opening sequence of an emergency call influences the efficiency of the ambulance dispatch time. The greeting sequences in 105 calls to a South African emergency service were analysed. Initial results suggested the advantage of a specific two-part opening sequence. An on-site experiment aimed at improving call efficiency was conducted during one shift (1100 calls). Results indicated reduced conversational repairs and a significant reduction of 4 seconds in mean call length. Implications for systems and training are derived. PMID- 26865541 TI - Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs. AB - Our study aimed to target adenoviral gene therapy to the uteroplacental circulation of pregnant guinea pigs in order to develop a novel therapy for fetal growth restriction. Four methods of delivery of an adenovirus encoding beta galactosidase (Ad.LacZ) were evaluated: intravascular injection using phosphate buffered saline (PBS) into (1) uterine artery (UtA) or (2) internal iliac artery or external administration in (3) PBS or (4) pluronic F-127 gel (Sigma Aldrich). Postmortem examination was performed 4 to 7 days after gene transfer. Tissue transduction was assessed by X-gal histochemistry and enzyme-linked immunosorbent assay. External vascular application of the adenovirus vector in combination with pluronic gel had 91.7% success rate in terms of administration (85% maternal survival) and gave the best results for maternal/fetal survival and local transduction efficiency without any spread to maternal or fetal tissues. This study suggests an optimal method of gene delivery to the UtAs of a small rodent for preclinical studies. PMID- 26865542 TI - Enhancing Adenoviral-Mediated Gene Transfer and Expression to Endometrial Cells. AB - OBJECTIVE: Our aim was to screen a panel of modified adenoviral gene transfer vectors to identify those which can sustain high gene expression in human endometrial cells. METHODS: Normal endometrial stromal cell cultures were established from endometrial lining of hysterectomy specimens performed for benign gynecologic indications. Human endometrial stromal cells were transfected by modified adenoviruses expressing luciferase reporter gene. Luciferase activity mediated by each virus was expressed as a percentage of adenovirus serotype 5 (Ad5-CMV-luc) activity. The 2-tailed Student t test was used to compare data. RESULTS: At a multiplicity of infection (MOI) of 10 pfu/cell, of the transductionally modified adenoviruses, adenovirus-RGD (Ad-RGD-luc) mediated highest level of endometrial cell transduction with transgene expression around 4 times higher when compared to Ad5 (P < .001). Of the transcriptionally targeted adenoviruses, adenovirus under secretory leukocyte protease inhibitor promoter (Ad-SLPI-luc) and adenovirus under heparanase promoter (Ad-heparanase-luc) mediated luciferase activation were 5.8- and 4.3-folds higher than Ad5-CMV-luc, respectively (P = .02 and .03, respectively). At MOI of 50 pfu/cell, Ad-RGD-luc and AD-SLPI-luc mediated significantly higher gene transfer efficiency compared to Ad5-CMV-luc (P values < .001, for each virus). Ad-heparanase-luc achieved higher gene activity, but difference was not significant (P = .1). Ad-SLPI-luc, at low viral dose (10 pfu/ cell), mediated gene expression effect comparable to Ad5-CMV-luc at a high dose (50 pfu/cell), with no significant difference. CONCLUSIONS: We conclude that when compared to the wild-type adenovirus, Ad-RGD luc, Ad-SLPI-luc, and Ad-heparanase-luc mediate higher reporter gene activity in endometrial cells and can work as effective gene transfer vectors in gene therapy applications to the endometrium. PMID- 26865544 TI - The Presence of Endometrioma Does Not Impair Time-Lapse Morphokinetic Parameters and Quality of Embryos: A Study On Sibling Oocytes. AB - OBJECTIVE: To see whether the oocytes retrieved from an ovary with an endometrioma would develop into embryos with aberrant timings of cleavage as assessed using time-lapse monitoring (TLM) and poorer morphologic quality compared with sibling oocytes from the contralateral ovary with no endometrioma in the same patient after intracytoplasmic sperm injection. METHODS: This was an observational prospective study at an in vitro fertilization (IVF) center of a private hospital. It included analysis and comparison of 128 embryos (69 embryos developed from the ovary with endometrioma and 59 embryos from the contralateral ovary without endometrioma serving as controls from a total of 20 women with infertility). Morphology of the embryo was assessed twice (days 3 and 5), again by capturing images with the TLM system. Morphokinetic parameters of embryos and clinical pregnancy rates were recorded separately from ovaries with and without endometrioma and were the primary outcomes of the study. Secondary outcomes included number of retrieved oocytes, number of metaphase II (MII) oocytes, fertilization rates, and conventional morphological classification of embryos. RESULTS: There were no differences in terms of the following time-lapse morphokinetic parameters of embryos. The mean numbers of oocytes and MII oocytes collected from the ovary with the endometrioma were similar to those collected from the contralateral ovary without endometrioma. Fertilization rates and the percentage of embryos with top morphologic quality were also similar. CONCLUSIONS: According to the morphokinetic parameters, this study further strengthens the notion that removal of endometriomas before IVF is not a necessity in terms of better oocyte quality and development. PMID- 26865543 TI - Aberrant HOXA10 Methylation in Patients With Common Gynecologic Disorders: Implications for Reproductive Outcomes. AB - HomeoboxA10 (HOXA10) is a transcription factor that is crucial for the development and patterning of the uterus during embryogenesis. In the adult endometrium, HOXA10 expression is regulated by steroid hormones and embryonic signals. Expression of sufficient HOXA10 messenger RNA is essential to endometrial receptivity and embryo implantation. Aberrant methylation is believed to alter the expression of HOXA10. Methylation of this gene may be associated with decreased fertility, implantation defects, and/or reproductive wastage seen in certain disease states that affect the female reproductive tract. This study describes the differences in methylation patterns of HOXA10 gene in uterine myomas, endometriosis, uterine septum, Asherman syndrome, or uterine polyps of women undergoing hysteroscopic surgery. In the endometrium of uteri with polyps, submucosal myomas, and intramural myomas, there were CpG sites within the HOXA10 gene that were highly methylated compared to controls. The HOXA10 gene in women with endometriosis was hypomethylated compared to controls. DNA methylation may be a common molecular mechanism that results in reproductive dysfunction seen in gynecologic disease. PMID- 26865546 TI - An Environmentally Sensitive Fluorescent Dye as a Multidimensional Probe of Amyloid Formation. AB - We have explored amyloid formation using poly(amino acid) model systems in which differences in peptide secondary structure and hydrophobicity can be introduced in a controlled manner. We show that an environmentally sensitive fluorescent dye, dapoxyl, is able to identify beta-sheet structure and hydrophobic surfaces, structural features likely to be related to toxicity, as a result of changes in its excitation and emission profiles and its relative quantum yield. These results show that dapoxyl is a multidimensional probe of the time dependence of amyloid aggregation, which provides information about the presence and nature of metastable aggregation intermediates that is inaccessible to the conventional probes that rely on changes in quantum yield alone. PMID- 26865549 TI - miR-21 promotes fibrosis in an acute cardiac allograft transplantation model. AB - AIMS: Cardiac transplantation is the only curative therapy for end-stage heart failure. Fibrosis is one of the major causes for impaired function of cardiac allografts. MicroRNAs, a class of small non-coding RNAs, play a critical role in the development of cardiovascular disease, but the role of microRNAs in cardiac allograft failure is not well understood. METHODS AND RESULTS: To uncover a role of microRNAs during cardiac graft fibrosis, we generated global microRNA profiles in allogeneic (BALB/c in C57BL/6N) and isogeneic (C57BL/6N in C57BL/6N) murine hearts after transplantation. miR-21 together with cardiac fibrosis was increased in cardiac allografts compared with isografts. Likewise, patients with cardiac rejection after heart transplantation showed increased cardiac miR-21 levels. miR 21 was induced upon treatment with IL-6 in a monocyte cell line. Overexpression of miR-21 in this monocyte cell line activated a fibrotic gene programme and promoted monocyte-to-fibrocyte transition together with activation of chemokine (C-C) motif ligand 2 (monocyte chemoattractant protein 1) via the phosphatase and tensin homologue/activator protein 1 regulatory axis. In vivo, both genetic and pharmacological inhibition of miR-21 successfully reduced fibrosis and fibrocyte accumulation in cardiac allografts. CONCLUSION: Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts. PMID- 26865545 TI - Concise Review: Mechanisms Behind Apoptotic Cell-Based Therapies Against Transplant Rejection and Graft versus Host Disease. AB - The main limitations to the success of transplantation are the antigraft response developed by the recipient immune system, and the adverse side effects of chronic immunosuppression. Graft-versus-host disease (GVHD) triggered by donor-derived T lymphocytes against the recipient tissues is another serious obstacle in the field of hematopoietic stem cell transplantation. Several laboratories have tested the possibility of promoting antigen (Ag)-specific tolerance for therapy of graft rejection, GVHD, and autoimmune disorders, by developing methodologies that mimic the mechanisms by which the immune system maintains peripheral tolerance in the steady state. It has been long recognized that the silent clearance of cells undergoing apoptosis exerts potent immune-regulatory effects and provides apoptotic cell-derived Ags to those Ag-presenting cells (APCs) that internalize them, in particular macrophages and dendritic cells. Therefore, in situ-targeting of recipient APCs by systemic administration of leukocytes in early apoptosis and bearing donor Ags represents a relatively simple approach to control the antidonor response against allografts. Here, we review the mechanisms by which apoptotic cells are silently cleared by phagocytes, and how such phenomenon leads to down-regulation of the innate and adaptive immunity. We discuss the evolution of apoptotic cell-based therapies from murine models of organ/tissue transplantation and GVHD, to clinical trials. We make emphasis on potential limitations and areas of concern of apoptotic cell-based therapies, and on how other immune-suppressive therapies used in the clinics or tested experimentally likely also function through the silent clearance of apoptotic cells by the immune system. Stem Cells 2016;34:1142-1150. PMID- 26865550 TI - Three-Year Pre-Post Analysis of EBP Integration in a Magnet-Designated Community Hospital. AB - BACKGROUND: Adoption of evidence-based practices (EBP) by registered nurses (RNs) and nurse leaders continues to be a challenge. Although multiple strategies and substantial resources are being invested to advance nursing practice based on evidence, little is known about the long-term impact of these interventions. AIMS: This study was undertaken to assess nurse leaders' and clinical RNs' beliefs to use EBP, perceptions about organizational readiness for EBP, and frequency of implementing EBP following implementation of multifaceted interventions to achieve and maintain Magnet designation. METHODS: This retrospective descriptive study compared data from two previously administered online surveys (2008 and 2012) at a mid-Atlantic Magnet-designated community hospital. RESULTS: Clinical RNs' self-reported attitudes toward EBP were more positive (2008: M = 53.85, standard error of the mean [SEM] = 0.65; 2012: M = 57.07,SEM = 0.58), as well as their perceptions of organizational readiness (2008: M = 50.72, SEM = 1.20; 2012: M = 81.09, SEM = 0.98), between the two survey years. Contrarily, although nurse leader scores were significantly higher for beliefs (2008: M = 61.15, SEM = 1.23; 2012: M = 60.60., SEM = 0.96), readiness (2008: M = 61.28, SEM = 2.16; 2012: M = 85.18, SEM = 1.64), and implementation (2008: M = 21.35, SEM = 1.72; 2012: M = 19.08, SEM = 1.43) little change was observed in the nurse leader scores between the two survey years compared with clinical RNs. DISCUSSION: Results from this study suggest that the multifaceted interventions have had a positive impact on clinical RNs' beliefs and readiness for EBP, but not for nurse leaders. Albeit low, self-reported implementation of EBP by RNs and nurse leaders has been sustained, but has not improved. LINKING EVIDENCE TO ACTION: Leaders must see their role as not only facilitators of EBP but also as active participants practicing EBP. Actively engaging leaders in EBP by serving on interprofessional EBP teams and role modeling these behaviors to staff is critical to EBP implementation. Realistic expectations of RNs for EBP implementation and clear and accessible resources may enhance RNs' willingness to implement. Going forward, it may be necessary to differentiate the expectations of RNs in EBP implementation by clarifying expectations in the process of identification and analysis of evidence from use of EBP in clinical practice. PMID- 26865552 TI - Notification of changes in taxonomic opinion previously published outside the IJSEM. PMID- 26865553 TI - Dermal myxopapillary ependymal rest in an adult. PMID- 26865559 TI - Unsafe and understudied: the US gun problem. PMID- 26865554 TI - Ocular Findings in Infants With Microcephaly Associated With Presumed Zika Virus Congenital Infection in Salvador, Brazil. AB - Importance: The Zika virus (ZIKV) has rapidly reached epidemic proportions, especially in northeastern Brazil, and has rapidly spread to other parts of the Americas. A recent increase in the prevalence of microcephaly in newborn infants and vision-threatening findings in these infants is likely associated with the rapid spread of ZIKV. Objective: To evaluate the ocular findings in infants with microcephaly associated with presumed intrauterine ZIKV infection in Salvador, Bahia, Brazil. Design, Setting, and Participants: Case series at a tertiary hospital. Twenty-nine infants with microcephaly (defined by a cephalic circumference of <=32 cm) with a presumed diagnosis of congenital ZIKV were recruited through an active search and referrals from other hospitals and health unities. The study was conducted between December 1 and December 21, 2015. Interventions: All infants and mothers underwent systemic and ophthalmic examinations from December 1 through December 21, 2015, in the Roberto Santos General Hospital, Salvador, Brazil. Anterior segment and retinal, choroidal, and optic nerve abnormalities were documented using a wide-field digital imaging system. The differential diagnosis included toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, syphilis, and human immunodeficiency virus, which were ruled out through serologic and clinical examinations. Main Outcomes and Measures: Ocular abnormalities associated with ZIKV. Results: Twenty three of 29 mothers (79.3%) reported suspected ZIKV infection signs and symptoms during pregnancy, 18 in the first trimester, 4 in the second trimester, and 1 in the third trimester. Of the 29 infants (58 eyes) examined (18 [62.1%] female), ocular abnormalities were present in 17 eyes (29.3%) of 10 children (34.5%). Bilateral findings were found in 7 of 10 patients presenting with ocular lesions, the most common of which were focal pigment mottling of the retina and chorioretinal atrophy in 11 of the 17 eyes with abnormalities (64.7%), followed by optic nerve abnormalities in 8 eyes (47.1%), bilateral iris coloboma in 1 patient (2 eyes [11.8%]), and lens subluxation in 1 eye (5.9%). Conclusions and Relevance: Congenital infection due to presumed ZIKV exposure is associated with vision-threatening findings, which include bilateral macular and perimacular lesions as well as optic nerve abnormalities in most cases. PMID- 26865560 TI - Performance of High Flow Rate Personal Respirable Samplers When Challenged with Mineral Aerosols of Different Particle Size Distributions. AB - It is thought that the performance of respirable samplers may vary when exposed to dust aerosols with different particle sizes and wind speeds. This study investigated the performance of the GK 4.16 (RASCAL), GK 2.69, PPI 8, and FSP 10, high flow rate personal samplers when exposed to aerosols of mineral dust in a wind tunnel at two different wind speeds (1 and 2 m s(-1)) and orientations (towards and side-on to the source of emission). The mass median aerodynamic diameter of four aerosolized test dusts ranged from 8 to 25 um with geometric standard deviations from 1.6 to 2 um. The performance of each sampler type was compared with that of the SIMPEDS (Higgins-Dewell design) sampler. There was slight evidence to suggest that the performance of the FSP 10 is affected by the direction of the inlet relative to the air flow, although this was not significant when most respirable dust concentrations were compared, possibly due to the variability of paired dust concentration results. The GK 2.69, RASCAL, and PPI 8 samplers had similar performances, although the results when side-on to the emission source were generally slightly lower than the SIMPEDS. Despite slight differences between respirable dust concentrations the respirable crystalline silica values were not significantly different from the SIMPEDS. The GK family of cyclones obtained most precise results and more closely matched the SIMPEDS. A comparison with dust concentration results from previous calm air chamber studies (where wind speeds were < 0.4 m s(-1)) found that the relative performance between samplers was similar to those observed in this work indicating consistent performance relative to the SIMPEDS in both calm and moving air. PMID- 26865561 TI - Multiscale Self-Assembly of Silicon Quantum Dots into an Anisotropic Three Dimensional Random Network. AB - Multiscale self-assembly is ubiquitous in nature but its deliberate use to synthesize multifunctional three-dimensional materials remains rare, partly due to the notoriously difficult problem of controlling topology from atomic to macroscopic scales to obtain intended material properties. Here, we propose a simple, modular, noncolloidal methodology that is based on exploiting universality in stochastic growth dynamics and driving the growth process under far-from-equilibrium conditions toward a preplanned structure. As proof of principle, we demonstrate a confined-but-connected solid structure, comprising an anisotropic random network of silicon quantum-dots that hierarchically self assembles from the atomic to the microscopic scales. First, quantum-dots form to subsequently interconnect without inflating their diameters to form a random network, and this network then grows in a preferential direction to form undulated and branching nanowire-like structures. This specific topology simultaneously achieves two scale-dependent features, which were previously thought to be mutually exclusive: good electrical conduction on the microscale and a bandgap tunable over a range of energies on the nanoscale. PMID- 26865563 TI - Erratum for the Research Article: "Complex effects of inhibiting hepatic apolipoprotein B100 synthesis in humans" by G. Reyes-Soffer, B. Moon, A. Hernandez-Ono, M. Dionizovick-Dimanovski, J. Jimenez, J. Obunike, T. Thomas, C. Ngai, N. Fontanez, D. S. Donovan, W. Karmally, S. Holleran, R. Ramakrishnan, R. S. Mittleman, H. N. Ginsberg. PMID- 26865562 TI - Monitoring Early-Stage Nanoparticle Assembly in Microdroplets by Optical Spectroscopy and SERS. AB - Microfluidic microdroplets have increasingly found application in biomolecular sensing as well as nanomaterials growth. More recently the synthesis of plasmonic nanostructures in microdroplets has led to surface-enhanced Raman spectroscopy (SERS)-based sensing applications. However, the study of nanoassembly in microdroplets has previously been hindered by the lack of on-chip characterization tools, particularly at early timescales. Enabled by a refractive index matching microdroplet formulation, dark-field spectroscopy is exploited to directly track the formation of nanometer-spaced gold nanoparticle assemblies in microdroplets. Measurements in flow provide millisecond time resolution through the assembly process, allowing identification of a regime where dimer formation dominates the dark-field scattering and SERS. Furthermore, it is shown that small numbers of nanoparticles can be isolated in microdroplets, paving the way for simple high-yield assembly, isolation, and sorting of few nanoparticle structures. PMID- 26865564 TI - Are Accurins the cure for Aurora kinase inhibitors? AB - A nanoparticle formulation of an Aurora B inhibitor increases antitumor efficacy and reduces toxicity, which may be a precedent for the use of this technology with other small molecules (Ashton et al., this issue). PMID- 26865551 TI - The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs. AB - The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-threat agents, and photoactivatable platinum(IV) complexes. Nanoparticles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations, including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers, will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also will reflect our optimism that the next generation of approved platinum cancer drugs is about to arrive. PMID- 26865565 TI - Aurora kinase inhibitor nanoparticles target tumors with favorable therapeutic index in vivo. AB - Efforts to apply nanotechnology in cancer have focused almost exclusively on the delivery of cytotoxic drugs to improve therapeutic index. There has been little consideration of molecularly targeted agents, in particular kinase inhibitors, which can also present considerable therapeutic index limitations. We describe the development of Accurin polymeric nanoparticles that encapsulate the clinical candidate AZD2811, an Aurora B kinase inhibitor, using an ion pairing approach. Accurins increase biodistribution to tumor sites and provide extended release of encapsulated drug payloads. AZD2811 nanoparticles containing pharmaceutically acceptable organic acids as ion pairing agents displayed continuous drug release for more than 1 week in vitro and a corresponding extended pharmacodynamic reduction of tumor phosphorylated histone H3 levels in vivo for up to 96 hours after a single administration. A specific AZD2811 nanoparticle formulation profile showed accumulation and retention in tumors with minimal impact on bone marrow pathology, and resulted in lower toxicity and increased efficacy in multiple tumor models at half the dose intensity of AZD1152, a water-soluble prodrug of AZD2811. These studies demonstrate that AZD2811 can be formulated in nanoparticles using ion pairing agents to give improved efficacy and tolerability in preclinical models with less frequent dosing. Accurins specifically, and nanotechnology in general, can increase the therapeutic index of molecularly targeted agents, including kinase inhibitors targeting cell cycle and oncogenic signal transduction pathways, which have to date proved toxic in humans. PMID- 26865568 TI - Self-reported suicide attempts and exposure to different types of violence and neglect during childhood: Findings from a young adult population survey in Latvia. AB - AIMS: Suicide rates in Latvia are among the highest in the EU. Among 18-25 year old young adults, it is the second leading cause of death. This study investigates the prevalence of self-reported suicide attempts in young adults and examines its association with neglect or violence of a physical, emotional or sexual nature. METHODS: A questionnaire was administered to 1259 young adults 18 25 years of age, selected by targeted quota sampling from secondary and vocational schools. RESULTS: The prevalence of self-reported suicide attempts was 6.1%. Physical and emotional adverse experiences showed clear associations with attempted suicide. Although prevalence of reported physical neglect was higher than for physical violence (27.0% versus 16.3%, respectively) the latter posed a higher risk for attempted suicide (OR = 4.0; 95% CI, 2.4-6.6). Conversely, emotional violence had a higher prevalence than emotional neglect (31.5% vs. 23.6%, respectively), but neglect showed a stronger association with attempted suicide (OR = 4.4; 95% CI, 2.6-7.3). CONCLUSIONS THE HIGH OR FOR ATTEMPTED SUICIDE ASSOCIATED WITH EMOTIONAL NEGLECT, TOGETHER WITH FINDINGS THAT EMOTIONAL VIOLENCE HAD THE HIGHEST PREVALENCE, AND THAT EMOTIONAL NEGLECT AND EMOTIONAL VIOLENCE SHOWED THE HIGHEST POPULATION ATTRIBUTABLE RISK FRACTION POPAR% OF 468 AND 404, RESPECTIVELY, SUGGESTED THAT EMOTIONAL FACTORS MERIT SPECIAL ATTENTION IN FURTHER INVESTIGATIONS OF ATTEMPTED SUICIDE AMONG YOUNG ADULTS IN LATVIA THE TARGETED QUOTA SAMPLING METHOD FROM FIVE CITIES REPRESENTING ALL REGIONS OF LATVIA AND 438% OF ITS POPULATION, ENSURE NATIONAL RELEVANCE OF OUR FINDINGS FOR POLICY AND PROGRAM DEVELOPMENT BY LEGISLATIVE, EDUCATIONAL AND PUBLIC HEALTH INSTITUTIONS. PMID- 26865567 TI - The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling. AB - Polymorphisms in FKBP51 are associated with stress-related psychiatric disorders and influence the severity of pain symptoms experienced after trauma. We report that FKBP51 (FK506 binding protein 51) is crucial for the full development and maintenance of long-term pain states. Indeed, FKBP51 knockout mice, as well as mice in which silencing of FKBP51 is restricted to the spinal cord, showed reduced hypersensitivity in several persistent pain models in rodents. FKBP51 deletion did not compromise the detection of acute painful stimuli, a critical protective mechanism. Moreover, the intrathecal administration of the specific FKBP51 inhibitor SAFit2 reduced the severity of an established pain state, confirming the crucial role of spinal FKBP51 in nociceptive processing. Finally, glucocorticoid signaling, which is known to modulate persistent pain states in rodents, was impaired in FKBP51 knockout mice. This finding suggested that FKBP51 regulates chronic pain by modulation of glucocorticoid signaling. Thus, FKBP51 is a central mediator of chronic pain, likely in humans as well as rodents, and is a new pharmacologically tractable target for the treatment of long-term pain states. PMID- 26865569 TI - 'We are all a little mad in one or other particular'. The presentation of madness in the novels of Muriel Spark. AB - This paper examines the presentation of madness in the novels of the great Scottish writer, Muriel Spark (1918-2006). In her work, there is a large cast of mad characters as well as a succession of psychiatrists and psychoanalysts. Spark suggests several explanations as to the origins of madness. We see mental disturbance conceived in terms of the supernatural, the religious and the Gothic. She also depicts insanity as a form of personality defect, eccentricity or mental enfeeblement. She drew on Romantic notions of the madman as a seer and speaker of truth. In her portrayal of psychiatrists, both the pill-prescribers and the psychoanalysts, Spark is frequently sceptical of the two: medication can erase positive qualities in an individual, and analysts can spout meaningless gibberish. PMID- 26865566 TI - Filaggrin inhibits generation of CD1a neolipid antigens by house dust mite derived phospholipase. AB - Atopic dermatitis is a common pruritic skin disease in which barrier dysfunction and cutaneous inflammation contribute to pathogenesis. Mechanisms underlying the associated inflammation are not fully understood, and although Langerhans cells expressing the nonclassical major histocompatibility complex (MHC) family member CD1a are known to be enriched within lesions, their role in clinical disease pathogenesis has not been studied. We observed that house dust mite (HDM) allergen generates neolipid antigens presented by CD1a to T cells in the blood and skin lesions of affected individuals. HDM-responsive CD1a-reactive T cells increased in frequency after birth in individuals with atopic dermatitis and showed rapid effector function, consistent with antigen-driven maturation. In HDM challenged human skin, we observed phospholipase A2 (PLA2) activity in vivo. CD1a reactive T cell activation was dependent on HDM-derived PLA2, and such cells infiltrated the skin after allergen challenge. Moreover, we observed that the skin barrier protein filaggrin, insufficiency of which is associated with atopic skin disease, inhibited PLA2 activity and decreased CD1a-reactive PLA2-generated neolipid-specific T cell activity from skin and blood. The most widely used classification schemes of hypersensitivity suggest that nonpeptide stimulants of T cells act as haptens that modify peptides or proteins; however, our results show that HDM proteins may also generate neolipid antigens that directly activate T cells. These data define PLA2 inhibition as a function of filaggrin, supporting PLA2 inhibition as a therapeutic approach. PMID- 26865570 TI - Reply to Mannacio et al. PMID- 26865571 TI - Individualized strategy for clopidogrel suspension in patients undergoing coronary surgery: is it the best choice? PMID- 26865573 TI - The Mind Matters: Psychology as an Overlooked Variable Within Physiology Studies. PMID- 26865574 TI - Discovery of Nitric Oxide and Translation to Clinical Application. PMID- 26865575 TI - Sex as a Biological Variable: Now What?! PMID- 26865572 TI - An open letter to The BMJ editors on qualitative research. PMID- 26865577 TI - If worst comes to horrible - sealing an iatrogenic coronary perforation with a polytetrafluoroethylene-covered stent in a patient with aspirin intolerance. AB - This report outlines the long-term outcome after successful sealing of a coronary perforation with a covered stent in a patient with aspirin allergy. PMID- 26865576 TI - Physiology in Perspective: Pursuing the Enchanted Loom of Motor Control. PMID- 26865578 TI - The anti-inflammatory effects of baicalin through suppression of NLRP3 inflammasome pathway in LPS-challenged piglet mononuclear phagocytes. AB - In this study, the anti-inflammatory effects and mechanisms of baicalin on LPS induced NLRP3 inflammatory pathway were investigated in piglet mononuclear phagocytes (control, LPS stimulation, LPS stimulation + 12.5 ug/ml baicalin, LPS stimulation + 25 ug/ml baicalin, LPS stimulation + 50 ug/ml baicalin and LPS stimulation + 100 ug/ml baicalin). The levels of reactive oxygen species (ROS), the secretion levels of IL-1beta, IL-18 and TNF-alpha, mRNA expression levels of IL-1beta, IL-18, TNF-alpha and NLRP3, as well as the protein levels of cleaved caspase-1 p20 were significantly increased after LPS-challengein vitro However, LPS stimulation did not influence apoptosis-associated speck-like protein and caspase-1 mRNA levels, which are also components of the NLRP3 inflammasome. Baicalin at 50 ug/ml and 100 ug/ml could inhibit the production of ROS, TNF alpha, IL-1beta and IL-18, and down-regulate mRNA expression of IL-1beta, IL-18, TNF-alpha and NLRP3, as well as expression of cleaved caspase-1 p20. These results showed that the anti-inflammatory effects of baicalin occurred via the regulation of the release of ROS and mRNA expression of NLRP3. The anti inflammatory activity of baicalin could be related to the suppression of NLRP3 inflammasome pathway under LPS stimulation. PMID- 26865579 TI - Medication to reduce breast cancer risk: why is uptake low? PMID- 26865580 TI - PARP inhibitor receives FDA breakthrough therapy designation in castration resistant prostate cancer: beyond germline BRCA mutations. PMID- 26865581 TI - Detection of Explosives Using Differential Laser-Induced Perturbation Spectroscopy with a Raman-based Probe. AB - Explosives detection is carried out with a novel spectral analysis technique referred to as differential laser-induced perturbation spectroscopy (DLIPS) on thin films of TNT, RDX, HMX, and PETN. The utility of Raman spectroscopy for detection of explosives is enhanced by inducing deep ultraviolet laser perturbation on molecular structures in combination with a differential Raman sensing scheme. Principal components analysis (PCA) is used to quantify the DLIPS method as benchmarked against a traditional Raman scattering probe, and the related photo-induced effects on the molecular structure of the targeted explosives are discussed in detail. Finally, unique detection is observed with TNT samples deposited on commonly available background substrates of nylon and polyester. Overall, the data support DLIPS as a noninvasive method that is promising for screening explosives in real-world environments and backgrounds. PMID- 26865582 TI - Laser-Induced Breakdown Spectroscopy (LIBS) for the Measurement of Spatial Structures and Fuel Distribution in Flames. AB - Laser-induced breakdown spectroscopy (LIBS) is used for the mapping of local structures (i.e., reactants and products zones) and for the determination of fuel distribution by means of the local equivalence ratio phi in laminar, premixed air hydrocarbon flames. The determination of laser threshold energy to induce breakdown in the different zones of flames is employed for the identification and demarcation of the local structures of a premixed laminar flame, while complementary results about fuel concentration were obtained from measurements of the cyanogen (CN) band Beta(2)Sigma(+)--Chi(2)Sigma(+), (Deltaupsilon = 0) at 388.3 nm and the ratio of the atomic lines of hydrogen (Halpha) and oxygen (O(I)), Halpha/O. The combination of these LIBS-based methods provides a relatively simple to use, rapid, and accurate tool for online and in situ combustion diagnostics, providing valuable information about the fuel distribution and the spatial variations of the local structures of a flame. PMID- 26865583 TI - EJE PRIZE 2015: How does insulin resistance arise, and how does it cause disease? Human genetic lessons. AB - Insulin orchestrates physiological responses to ingested nutrients; however, although it elicits widely ramifying metabolic and trophic responses from diverse tissues, 'insulin resistance (IR)', a pandemic metabolic derangement commonly associated with obesity, is usually defined solely by blunting of insulin's hypoglycaemic effect. Recent study of monogenic forms of IR has established that biochemical subphenotypes of IR exist, clustering into those caused by primary disorders of adipose tissue and those caused by primary defects in proximal insulin signalling. IR is often first recognised by virtue of its associated disorders including type 2 diabetes, dyslipidaemia (DL), fatty liver and polycystic ovary syndrome (PCOS). Although these clinically observed associations are confirmed by cross-sectional and longitudinal population-based studies, causal relationships among these phenomena have been more difficult to establish. Single gene IR is important to recognise in order to optimise clinical management and also permits testing of causal relationships among components of the IR syndrome using the principle of Mendelian randomisation. Thus, where a precisely defined genetic defect is identified that directly produces one component of the syndrome, then phenomena that are causally linked to that component should be seen. Where this is not the case, then a simple causal link is refuted. This article summarises known forms of monogenic severe IR and considers the lessons to be learned about the pathogenic mechanisms both upstream from common IR and those downstream linking it to disorders such as DL, fatty liver, PCOS and cancer. PMID- 26865584 TI - Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency. AB - OBJECTIVE: To comprehensively characterize androgens and androgen precursors in classic 21-hydroxylase deficiency (21OHD) and to gain insights into the mechanisms of their formation. DESIGN: Serum samples were obtained from 38 patients (19 men) with classic 21OHD, aged 3-59, and 38 sex- and age-matched controls; 3 patients with 11beta-hydroxylase deficiency; 4 patients with adrenal insufficiency; and 16 patients (8 men) undergoing adrenal vein sampling. Paraffin embedded normal (n = 5) and 21OHD adrenal tissues (n = 3) were used for immunohistochemical studies. METHODS: We measured 11 steroids in all sera by liquid chromatography-tandem mass spectrometry. Immunofluroescence localized 3beta-hydroxysteroid dehydrogenase type 2 (HSD3B2) and cytochrome b5 (CYB5A) within the normal and 21OHD adrenals. RESULTS: Four 11-oxygenated 19-carbon (11oxC19) steroids were significantly higher in male and female 21OHD patients than in controls: 11beta-hydroxyandrostenedione, 11-ketoandrostenedione 11beta hydroxytestosterone, and 11-ketotestosterone (3-4-fold, P < 0.0001). For 21OHD patients, testosterone and 11-ketotestosterone were positively correlated in females, but inversely correlated in males. All 11oxC19 steroids were higher in the adrenal vein than in the inferior vena cava samples from men and women and rose with cosyntropin stimulation. Only trace amounts of 11oxC19 steroids were found in the sera of patients with 11beta-hydroxylase deficiency and adrenal insufficiency, confirming their adrenal origin. HSD3B2 and CYB5A immunoreactivities were sharply segregated in the normal adrenal glands, whereas areas of overlapping expression were identified in the 21OHD adrenals. CONCLUSIONS: All four 11oxC19 steroids are elevated in both men and women with classic 21OHD. Our data suggest that 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess. PMID- 26865585 TI - Diffuse parathyroid hormone expression in parathyroid tumors argues against important functional tumor subclones. AB - OBJECTIVE: Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium-PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23. DESIGN: A total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR. RESULTS: Low tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25 hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH. CONCLUSIONS: No areas with apparently higher PTH expression were identified, perhaps suggesting that hyper functioning parathyroid tumor subclones should be rare. Circulating 25 hydroxyvitamin D levels may influence tumor PTH expression in vivo. If PTH immunoreactivity reflects the tumor calcium-PTH set point, our data imply that the main determinant of disease severity should be tumor weight. PMID- 26865586 TI - Relation of Plasma Fibrinogen Level With the Presence, Severity, and Complexity of Coronary Artery Disease. AB - BACKGROUND: Relation of plasma fibrinogen levels with extent, severity, and complexity of coronary artery disease (CAD) in patients with stable angina pectoris (SAP) has not been adequately investigated. The aim of this study was to evaluate whether plasma fibrinogen level is associated with coronary complexity, severity, and extent assessed by SYNTAX (Synergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery) score (SS). METHODS: We enrolled 134 consecutive patients with SAP who underwent coronary angiography. Baseline serum fibrinogen levels were measured, and SS was calculated from the study population. The patients were classified into 3 groups by tertiles of SS (SS, control group = 0; intermediate group < 22; and high group >= 22). RESULTS: Plasma fibrinogen levels demonstrated a stepwise increase from control group to high SS group. There was a strong correlation between fibrinogen and the SS ( r = .535, P < .001). Area under the receivers operating characteristic curve of fibrinogen was 0.72 (95% confidence interval [CI] 0.61-0.82; < .001) for predicting a high SS. Fibrinogen value higher than 411 mg/dL has a sensitivity of 75% and a specificity of 64% in prediction of high SS. In multivariate analyses, plasma fibrinogen was observed to be an independent predictor for high SS in patients with stable CAD (odds ratio [OR] 1.01; 95% CI, 1.01-1.02; P < .001). CONCLUSION: Plasma fibrinogen is a readily measurable systemic inflammatory marker and is independently associated coronary severity and complexity in patients with CAD. PMID- 26865587 TI - Obesity and Breast Cancer: Molecular Interconnections and Potential Clinical Applications. AB - Obesity is an important risk factor for breast cancer (BC) in postmenopausal women; interlinked molecular mechanisms might be involved in the pathogenesis. Increased levels of estrogens due to aromatization of the adipose tissue, inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and prostaglandin E2, insulin resistance and hyperactivation of insulin-like growth factors pathways, adipokines, and oxidative stress are all abnormally regulated in obese women and contribute to cancerogenesis. These molecular factors interfere with intracellular signaling in the mitogen-activated protein kinase and phosphatydilinositol-3-phosphate/mammalian target of rapamycin (mTOR) pathways, which regulate the progression of the cell cycle, apoptosis, and protein synthesis. In this context, structural defects of typical genes related to both BC and obesity, such as leptin, leptin receptor, serum paraoxonase/arylesterase 1, the fat mass and obesity-associated gene and melanocortin receptor 4, have been associated with a high or low risk of BC development. The early detection of these gene alterations might be useful as risk predictors in obese women, and targeting these pathways involved in the BC pathogenesis in obese women is a potential therapeutic tool. In particular, mTOR pathway deregulation concurs in both obesity and BC, and inhibition of this might disrupt the molecular interlinks in a similar manner to that of metformin, which exerts definite anticancer activity and is currently used as an antidiabetic drug with a weight-reducing property. The identification of both genetic and pharmacological implications on the prevention and management of BC is the ultimate aim of these studies. IMPLICATIONS FOR PRACTICE: Obese women are at risk of breast cancer, but clinicians lack concrete tools for the prevention or early diagnosis of this risk. The present study, starting from the biology and the molecular defects characterizing both obesity and breast cancer, analyzed the potential molecules and genetic defects whose early identification could delineate a risk profile. Three steps are proposed that are potentially achievable in the clinical assessment of obese women, namely the evaluation of altered levels of serum molecules, the identification of genetic polymorphisms, and the study of the transcriptomic profile of premalignant lesions. Finally, the therapeutic implications of this molecular assessment were evaluated. PMID- 26865588 TI - Occupational Therapy for Adults With Cancer: Why It Matters. AB - Adults with cancer may be at risk for limitations in functional status and quality of life (QOL). Occupational therapy is a supportive service with the specific mission to help people functionally engage in life as safely and independently as possible with the primary goal of improving QOL. Unfortunately, for people with cancer, occupational therapy remains underused. The overall purpose of this review is to provide an understanding of what occupational therapy is and its relevance to patients with cancer, highlight the reasons to refer, and, last, provide general advice on how to access services. PMID- 26865589 TI - Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes for Early Breast Cancer According to Disease Subtypes: Sensitivity Analysis of Randomized Trials in Adjuvant and Neoadjuvant Setting. AB - BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is still an issue for clinical research. Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes. METHODS: Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10% incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype. RESULTS: Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p < .0001) according to LPBC was found. The presence of LPBC was associated with a 29.5% increase in pCR rate compared with non-LPBC (p < .0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7% (95% confidence interval [CI], 4.9%-26.2%) and 33.3% (95% CI, 23.6%-42.7%), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p < .0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p < .0001), with no statistically significant difference for estrogen receptor-positive/HER2 negative disease. CONCLUSION: Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2-positive disease. PMID- 26865590 TI - Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients. AB - BACKGROUND: Patient blood management (PBM) programs are associated with reduced transfusion usage, reduced hospital costs, and improved patient outcomes. The application of PBM principles in patients with malignant disease might achieve similar results. However, this population presents unique challenges. The aim of the present study was to investigate the impact of a PBM program on blood usage and patient outcomes in cancer patients, particularly in the setting of restricted use of erythropoiesis-stimulating agents (ESAs). MATERIALS AND METHODS: A retrospective observational study was performed of patients admitted with a primary diagnosis of malignancy treated at Eastern Maine Medical Center as inpatients or outpatients, or both, from January 2008 through July 2013. RESULTS: The proportion of inpatients and outpatients receiving ESAs decreased from 2.9% in 2008 to 1.1% in 2013 (p < .001). During the same period, an increase occurred in the mean dose of intravenous (IV) iron from 447 mg (95% confidence interval [CI], 337-556) to 588 mg (95% CI, 458-718). The mean red blood cell (RBC) units transfused per inpatient and outpatient episode decreased from 0.067 to 0.038 unit (p < .001). In inpatients, significant increases occurred in the proportion of single-unit RBC transfusions (p < .001) and patients infused with IV iron (p = .02), and significant decreases in the mean pretransfusion hemoglobin (p = .02) and RBC transfusion rate (p = .04). In-hospital mortality and length of stay did not change significantly during this period. CONCLUSION: Despite the decreased use of ESA therapy, the implementation of a PBM program and outpatient anemia management protocol in cancer patients at our medical center was associated with significant reductions in RBC usage. PMID- 26865591 TI - The Clinical and Economic Impacts of Skeletal-Related Events Among Medicare Enrollees With Prostate Cancer Metastatic to Bone. AB - BACKGROUND: Approximately 40% of men diagnosed with metastatic prostate cancer experience one or more skeletal-related events (SREs), defined as a pathological fracture, spinal cord compression, or surgery or radiotherapy to the bone. Accurate assessment of their effect on survival, health care resource utilization (HCRU), and cost may elucidate the value of interventions to prevent SREs. MATERIALS AND METHODS: Men older than age 65 years with prostate cancer and bone metastasis diagnosed between 2004 and 2009 were identified from linked Surveillance Epidemiology and End Results-Medicare records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk for death associated with SREs were calculated by using Cox regression. HCRU and costs (in 2013 U.S. dollars) were evaluated in a propensity score-matched cohort by using Poisson regression and Kaplan-Meier sample average estimators, respectively. RESULTS: Among 3,297 men with prostate cancer metastatic to bone, 40% experienced >=1 SRE (median follow-up, 19 months). Compared with men who remained SRE-free, men with >=1 SRE had a twofold higher risk for death (HR, 2.29; 95% CI, 2.09-2.51). Pathological fracture was associated with the highest risk for death (HR, 2.77; 95% CI, 2.38 3.23). Among men with >=1 SRE, emergency department visits were twice as frequent (95% CI, 1.77-2.28) and hospitalizations were nearly four times as frequent (95% CI, 3.20-4.40). The attributable cost of >=1 SRE was $21,191 (>=1 SRE: $72,454 [95% CI, $67,362-$76,958]; SRE-free: $51,263 [95% CI, $45,439-$56,100]). CONCLUSION: Among men with prostate cancer metastatic to bone, experiencing >=1 SRE is associated with poorer survival, increased HCRU, and increased costs. These negative effects emphasize the importance of SRE prevention in this population. PMID- 26865592 TI - Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects. AB - Shigella causes high morbidity and mortality worldwide, but there is no licensed vaccine for shigellosis yet. We evaluated the safety and immunogenicity of a formalin-inactivated whole-cell Shigella flexneri2a vaccine, Sf2aWC, given orally to adult volunteers. In a double-blind, placebo-controlled trial, 82 subjects were randomized to receive three doses of vaccine in dose escalation (2.6 +/- 0.8 * 10(8), * 10(9), * 10(10), and * 10(11)vaccine particles/ml). Vaccine safety was actively monitored, and antigen-specific systemic and mucosal immune responses were determined in serum, antibody in lymphocyte supernatant (ALS), and fecal samples. Cytokines were measured in the serum. Sf2aWC was well tolerated and generally safe at all four dose levels. The vaccine resulted in a dose-dependent immune response. At the highest dose, the vaccine induced robust responses to lipopolysaccharide (LPS) in both serum and ALS samples. The highest magnitude and frequency of responses occurred after the first dose in almost all samples but was delayed for IgG in serum. Fifty percent of the vaccinees had a >4-fold increase in anti-LPS fecal antibody titers. Responses to invasion plasmid antigens (Ipa) were low. The levels of interleukin-17 (IL-17), IL-2, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10 were increased, and IL-8 was decreased immediately after first dose, but these changes were very transient. This phase I trial demonstrated that the Sf2aWC vaccine, a relatively simple vaccine concept, was safe and immunogenic. The vaccine elicited immune responses which were comparable to those induced by a live, attenuated Shigella vaccine that was protective in prior human challenge studies. PMID- 26865593 TI - Coexistent Malnutrition Is Associated with Perturbations in Systemic and Antigen Specific Cytokine Responses in Latent Tuberculosis Infection. AB - Malnutrition, as defined by low body mass index (BMI), is a major risk factor for the development of active tuberculosis (TB), although the biological basis underlying this susceptibility remains poorly characterized. To verify whether malnutrition affects the systemic and antigen-specific cytokine levels in individuals with latent TB (LTB), we examined circulating and TB antigen stimulated levels of cytokines in individuals with LTB and low BMI (LBMI) and compared them with those in individuals with LTB and normal BMI (NBMI). Coexistent LBMI with LTB was characterized by diminished circulating levels of type 1 (gamma interferon [IFN-gamma] and tumor necrosis factor alpha [TNF alpha]), type 2 (interleukin-4 [IL-4]), type 17 (IL-22), and other proinflammatory (IL-1alpha, IL-1beta, and IL-6) cytokines but elevated levels of other type 2 (IL-5 and IL-13) and regulatory (IL-10 and transforming growth factor beta [TGF-beta]) cytokines. In addition, LBMI with LTB was associated with diminished TB antigen-induced IFN-gamma, TNF-alpha, IL-6, IL-1alpha, and IL-1beta levels. Finally, there was a significant positive correlation between BMI values and TNF-alpha and IL-1beta levels and a significant negative correlation between BMI values and IL-2, IL-10, and TGF-beta levels in individuals with LTB. Therefore, our data reveal that latent TB with a coexistent low BMI is characterized by diminished protective cytokine responses and heightened regulatory cytokine responses, providing a potential biological mechanism for the increased risk of developing active TB. PMID- 26865594 TI - Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans. AB - Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-gamma) and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-gamma, IL-2, IL-4, IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1 Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7,r(2)= 0.86,P< 0.0001, log10 transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. NCT00119067.). PMID- 26865595 TI - Cellular Immune Responses in Humans Induced by Two Serogroup B Meningococcal Outer Membrane Vesicle Vaccines Given Separately and in Combination. AB - MenBvac and MeNZB are safe and efficacious outer membrane vesicle (OMV) vaccines against serogroup B meningococcal disease. Antibody responses have previously been investigated in a clinical trial with these two OMV vaccines given separately (25 MUg/dose) or in combination (12.5 and 12.5 MUg/dose) in three doses administered at 6-week intervals. Here, we report the results from analyzing cellular immune responses against MenBvac and MeNZB OMVs in terms of antigen-specific CD4(+)T cell proliferation and secretion of cytokines. The proliferative CD4(+)T cell responses to the combined vaccine were of the same magnitude as the homologous responses observed for each individual vaccine. The results also showed cross-reactivity in the sense that both vaccine groups receiving separate vaccines responded to both homologous and heterologous OMV antigen when assayed for antigen-specific cellular proliferation. In addition, a multiplex bead array assay was used to analyze the presence of Th1 and Th2 cytokines in cell culture supernatants. The results showed that gamma interferon, interleukin-4 (IL-4), and IL-10 responses could be detected as a result of vaccination with both the MenBvac and the MeNZB vaccines given separately, as well as when given in combination. With respect to cross-reactivity, the cytokine results paralleled the observations made for proliferation. In conclusion, the results demonstrate that cross-reactive cellular immune responses involving both Th1 and Th2 cytokines can be induced to the same extent by different tailor-made OMV vaccines given either separately or in combination with half the dose of each vaccine. PMID- 26865596 TI - Potent In Vitro and In Vivo Activity of Plantibody Specific for Porphyromonas gingivalis FimA. AB - Fimbrial protein fimbrillin (FimA), a major structural subunit of Porphyromonas gingivalis, has been suggested as a vaccine candidate to control P. gingivalis induced periodontal disease. Previously, cDNAs encoding IgG monoclonal antibodies (MAbs) against purified FimA from P. gingivalis 2561 have been cloned, and the MAbs have been produced in rice cell suspension. Here we examined the biological activities of the plant-produced MAb specific for FimA (anti-FimA plantibody) of P. gingivalis in vitro and in vivo. The anti-FimA plantibody recognized oligomeric/polymeric forms of native FimA in immunoblot analysis and showed high affinity for native FimA (KD = 0.11 nM). Binding of P. gingivalis (10(8) cells) to 2 mg of saliva-coated hydroxyapatite beads was reduced by 53.8% in the presence of 1 MUg/ml plantibody. Anti-FimA plantibody (10 MUg/ml) reduced invasion of periodontal ligament cells by P. gingivalis (multiplicity of infection, 100) by 68.3%. Intracellular killing of P. gingivalis opsonized with the anti-FimA plantibody by mouse macrophages was significantly increased (77.1%) compared to killing of bacterial cells with irrelevant IgG (36.7%). In a mouse subcutaneous chamber model, the number of recoverable P. gingivalis cells from the chamber fluid was significantly reduced when the numbers of bacterial cells opsonized with anti-FimA plantibody were compared with the numbers of bacterial cells with irrelevant IgG, 66.7% and 37.1%, respectively. These in vitro and in vivo effects of anti-FimA plantibody were comparable to those of the parental MAb. Further studies with P. gingivalis strains with different types of fimbriae are needed to investigate the usefulness of anti-FimA plantibody for passive immunization to control P. gingivalis-induced periodontal disease. PMID- 26865598 TI - Response to: 'Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women' by Gao et al. PMID- 26865597 TI - Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis. AB - Invasive nontyphoidal Salmonella (iNTS) disease is a neglected disease with high mortality in children and HIV-positive individuals in sub-Saharan Africa, caused primarily by Africa-specific strains of Salmonella enterica serovars Typhimurium and Enteritidis. A vaccine using GMMA (generalized modules for membrane antigens) fromS.Typhimurium andS.Enteritidis containing lipid A modifications to reduce potential in vivo reactogenicity is under development. GMMA with penta-acylated lipid A showed the greatest reduction in the level of cytokine release from human peripheral blood monocytes from that for GMMA with wild-type lipid A. Deletion of the lipid A modification genes msbB and pagP was required to achieve pure penta acylation. Interestingly, DeltamsbBDelta pagP GMMA from S. Enteritidis had a slightly higher stimulatory potential than those from S. Typhimurium, a finding consistent with the higher lipopolysaccharide (LPS) content and Toll-like receptor 2 (TLR2) stimulatory potential of the former. Also, TLR5 ligand flagellin was found in Salmonella GMMA. No relevant contribution to the stimulatory potential of GMMA was detected even when the flagellin protein FliC from S. Typhimurium was added at a concentration as high as 10% of total protein, suggesting that flagellin impurities are not a major factor for GMMA-mediated immune stimulation. Overall, the stimulatory potential of S. Typhimurium and S. Enteritidis DeltamsbB DeltapagP GMMA was close to that of Shigella sonnei GMMA, which are currently in phase I clinical trials. PMID- 26865599 TI - Predictive validity of the ASAS classification criteria for axial and peripheral spondyloarthritis after follow-up in the ASAS cohort: a final analysis. AB - OBJECTIVE: To establish the predictive validity of the Assessment of SpondyloArthritis international Society (ASAS) spondyloarthritis (SpA) classification criteria. METHODS: 22 centres (N=909 patients) from the initial 29 ASAS centres (N=975) participated in the ASAS-cohort follow-up study. Patients had either chronic (>3 months) back pain of unknown origin and age of onset below 45 years (N=658) or peripheral arthritis and/or enthesitis and/or dactylitis (N=251). At follow-up, information was obtained at a clinic visit or by telephone. The positive predictive value (PPV) of the baseline classification by the ASAS criteria was calculated using rheumatologist's diagnosis at follow-up as external standard. RESULTS: In total, 564 patients were assessed at follow-up (345 visits; 219 telephone) with a mean follow-up of 4.4 years (range: 1.9; 6.8) and 70.2% received a SpA diagnosis by the rheumatologist. 335 patients fulfilled the axial SpA (axSpA) or peripheral SpA (pSpA) criteria at baseline and of these, 309 were diagnosed SpA after follow-up (PPV SpA criteria: 92.2%). The PPV of the axSpA and pSpA criteria was 93.3% and 89.5%, respectively. The PPV for the 'clinical arm only' was 88.0% and for the 'clinical arm'+/-'imaging arm' 96.0%, for the 'imaging arm only' 86.2% and for the 'imaging arm'+/-'clinical arm' 94.7%. A series of sensitivity analyses yielded similar results (range: 85.1 98.2%). CONCLUSIONS: The PPV of the axSpA and pSpA criteria to forecast an expert's diagnosis of 'SpA' after more than 4 years is excellent. The 'imaging arm' and 'clinical arm' of the axSpA criteria have similar predictive validity and are truly complementary. PMID- 26865600 TI - Antibodies to native and citrullinated RA33 (hnRNP A2/B1) challenge citrullination as the inciting principle underlying loss of tolerance in rheumatoid arthritis. AB - BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) are the hallmark of rheumatoid arthritis (RA). Protein citrullination is believed to drive autoantigen selection in RA. Nonetheless, several autoantigens in RA are targeted as native (unmodified) proteins. Here, the study of hnRNP A2/B1 (RA33) provides a framework to understand the humoral response to native and citrullinated autoantigens in RA. METHODS: RA synovial fluid (SF) cells were analysed by immunoblotting and mass spectrometry. RA33 was cloned from RASF cells and splice variants expressed as recombinant proteins. Antibodies against native and citrullinated RA33 were characterised by ELISA, immunoblotting and immunoprecipitation. RESULTS: RA33 is citrullinated in the rheumatoid joint and targeted either as a citrullinated or native protein in distinct patient subsets with RA. A novel splice variant (hnRNP B1b) previously associated with disease initiation in experimental arthritis was identified in the RA joint and acts as the major target of the anti-RA33 response. Antibodies exclusively targeting citrullinated RA33 were positively associated with disease duration and erosive disease. In contrast, anti-(native) RA33 antibodies were detected almost exclusively in early RA and identified patients with low radiographic erosion scores. Finally, a unique subset of double-reactive patients demonstrated intermediate severity, but rapid disease progression, suggesting a transitional disease phase in the evolution of an anti-native protein antibody to ACPA response in RA. CONCLUSIONS: These data suggest that native and citrullinated proteins targeted by autoantibodies in RA may be part of a single antibody system and challenge the paradigm of citrullination as the unifying principle underlying loss of tolerance in RA. PMID- 26865601 TI - Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis. AB - OBJECTIVES: To assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients achieving Disease Activity Score (DAS)-defined remission or low disease activity. METHODS: Patients with early, active RA were randomised to ABA plus methotrexate (ABA/MTX) 125 mg/week, ABA 125 mg/week or MTX for 12 months. All RA treatments were withdrawn after 12 months in patients with DAS28 (C reactive protein (CRP)) <3.2. Adjusted mean changes from baseline in MRI-based synovitis, osteitis and erosion were calculated for the intention-to-treat population. RESULTS: 351 patients were randomised and treated: ABA/MTX (n=119), ABA (n=116) or MTX (n=116). Synovitis and osteitis improved, and progression of erosion was statistically less with ABA/MTX versus MTX at month 12 (-2.35 vs -0.68, -2.58 vs 0.68, 0.19 vs 1.53, respectively; p<0.01 for each) and month 18 (-1.34 vs -0.49 2.03 vs 0.34, 0.13 vs 2.0, respectively; p<0.01 for erosion); ABA benefits were numerically intermediate to those for ABA/MTX and MTX. CONCLUSIONS: Structural benefits with ABA/MTX or ABA may be maintained 6 months after withdrawal of all treatments in patients who have achieved remission or low disease activity. TRIAL REGISTRATION NUMBER: NCT01142726; Results. PMID- 26865602 TI - Effect of Prayer on Intensity of Migraine Headache: A Randomized Clinical Trial. AB - BACKGROUND AND AIM: Migraine is a common form of headache that affects patients quality of life negatively. In addition to pharmacologic treatment, there are a variety of nonpharmacologic treatments for migraine headache. In present study, we examined the effect of prayer on intensity of migraine pain. METHODS: In a prospective, randomized, controlled trial from October 2013 to June 2014, this study has been conducted in Kerman, Iran. We randomly assigned 92 patients in 2 groups to receive either 40 mg of propranolol twice a day for 2 month (group "A") or 40 mg of propranolol twice a day for 2 months with prayer (group "B"). At the beginning of study and 3 months after intervention, patients' pain was measured using the visual analogue scale. RESULTS: At the beginning of study and before intervention, the mean score of pain in patients in groups A and B were 5.7 +/- 1.6 and 6.5 +/- 1.9, respectively. According to results of independent t test, mean score of pain intensity at the beginning of study were similar between patients in 2 groups (P > .05). Three month after intervention, mean score of pain intensity decreased in patients in both groups. At this time, the mean scores of pain intensity were 5.4 +/- 1.1 and 4.2 +/- 2.3 in patients in groups A and B, respectively. This difference between groups was statistically significant (P < .001). CONCLUSIONS: The present study revealed that prayer can be used as a nonpharmacologic pain coping strategy in addition to pharmacologic intervention for this group of patients. PMID- 26865603 TI - End-of-life care in oxygen-dependent ILD compared with lung cancer: a national population-based study. AB - RATIONALE: Advanced fibrosing interstitial lung disease (ILD) is often progressive and associated with a high burden of symptoms and poor prognosis. Little is known about the symptom prevalence and access to palliative care services at end of life (EOL). OBJECTIVES: Compare prevalence of symptoms and palliative treatments between patients dying with oxygen-dependent ILD and patients dying of lung cancer. METHODS: Nationwide registry-based cohort study of patients with oxygen-dependent ILD and patients with lung cancer who died between 1 January 2011 and 14 October 2013. Prevalence of symptoms and treatments during the last seven days of life were compared using data in Swedish Registry of Palliative Care. MEASUREMENTS AND MAIN RESULTS: 285 patients with ILD and 10 822 with lung cancer were included. In ILD, death was more likely to be 'unexpected' (15% vs 4%), less likely to occur in a palliative care setting (17% vs 40%) and EOL discussions with the patients (41% vs 59%) were less common than in lung cancer. Patients with ILD suffered more from breathlessness (75% vs 42%) while patients with lung cancer had more pain (51% vs 73%) (p<0.005 for all comparisons). Patients with ILD had more unrelieved breathlessness, pain and anxiety. The survival time from initiation of oxygen therapy in ILD was a median 8.4 months (IQR 3.4-19.2 months). CONCLUSIONS: Patients with ILD receive poorer access to specialist EOL care services and experience more breathlessness than patients with lung cancer. This study highlights the need of better EOL care in oxygen-dependent ILD. PMID- 26865604 TI - Does Correlated Firing Underlie Attention Deployment in Frontal Cortex? PMID- 26865605 TI - Studying Mesodiencephalic Dopaminergic Neuron Development In Vivo to Improve Stem Cell Therapy in Parkinson's Disease. PMID- 26865606 TI - Distinct Mechanisms for Distractor Suppression and Target Facilitation. AB - It is well established that preparatory attention improves processing of task relevant stimuli. Although it is often more important to ignore task-irrelevant stimuli, comparatively little is known about preparatory attentional mechanisms for inhibiting expected distractions. Here, we establish that distractor inhibition is not under the same top-down control as target facilitation. Using a variant of the Posner paradigm, participants were cued to either the location of a target stimulus, the location of a distractor, or were provided no predictive information. In Experiment 1, we found that participants were able to use target relevant cues to facilitate target processing in both blocked and flexible conditions, but distractor cueing was only effective in the blocked version of the task. In Experiment 2, we replicate these findings in a larger sample and leveraged the additional statistical power to perform individual differences analyses to tease apart potential underlying mechanisms. We found no evidence for a correlation between these two types of benefit, suggesting that flexible target cueing and distractor suppression depend on distinct cognitive mechanisms. In Experiment 3, we use EEG to show that preparatory distractor suppression is associated with a diminished P1, but we found no evidence to suggest that this effect was mediated by top-down control of oscillatory activity in the alpha band (8-12 Hz). We conclude that flexible top-down mechanisms of cognitive control are specialized for target-related attention, whereas distractor suppression only emerges when the predictive information can be derived directly from experience. This is consistent with a predictive coding model of expectation suppression. SIGNIFICANCE STATEMENT: If you were told to ignore a white bear, you might find it quite difficult. Holding something in working memory is thought to automatically facilitate feature processing, even if doing so is detrimental to the current task. Despite this paradox, it is often assumed that distractor suppression is controlled via similar top-down mechanisms of attention that prepare brain areas for target enhancement. In particular, low-frequency oscillations in visual cortex appear especially well suited for gating task irrelevant information. We describe the results of a series of studies exploring distractor suppression and challenge this popular notion. We draw on behavioral and EEG evidence to show that selective distractor suppression operates via an alternative mechanism, such as expectation suppression within a predictive coding framework. PMID- 26865607 TI - Age-Related Changes in Frontal Network Structural and Functional Connectivity in Relation to Bimanual Movement Control. AB - Changes in both brain structure and neurophysiological function regulating homotopic as well as heterotopic interhemispheric interactions (IHIs) are assumed to be responsible for the bimanual performance deficits in older adults. However, how the structural and functional networks regulating bimanual performance decline in older adults, as well as the interplay between brain structure and function remain largely unclear. Using a dual-site transcranial magnetic stimulation paradigm, we examined the age-related changes in the interhemispheric effects from the dorsolateral prefrontal cortex and dorsal premotor cortex onto the contralateral primary motor cortex (M1) during the preparation of a complex bimanual coordination task in human. Structural properties of these interactions were assessed with diffusion-based fiber tractography. Compared with young adults, older adults showed performance declines in the more difficult bimanual conditions, less optimal brain white matter (WM) microstructure, and a decreased ability to regulate the interaction between dorsolateral prefrontal cortex and M1. Importantly, we found that WM microstructure, neurophysiological function, and bimanual performance were interrelated in older adults, whereas only the task related changes in IHI predicted bimanual performance in young adults. These results reflect unique interactions between structure and function in the aging brain, such that declines in WM microstructural organization likely lead to dysfunctional regulation of IHI, ultimately accounting for bimanual performance deficits. SIGNIFICANCE STATEMENT: The structural and functional changes in the aging brain are associated with a decline in movement control, compromising functional independence. We used MRI and noninvasive brain stimulation techniques to investigate white matter microstructural organization and neurophysiological function in the aging brain, in relation to bimanual movement control. We found that less optimal brain microstructural organization and task-related modulations in neurophysiological function resulted in poor bimanual performance in older adults. By interrelating brain structure, neurophysiological function, and behavior, the current study provides a comprehensive picture of biological alterations in the aging brain that underlie declines in bimanual performance. PMID- 26865608 TI - QRFP and Its Receptors Regulate Locomotor Activity and Sleep in Zebrafish. AB - The hypothalamus plays an important role in regulating sleep, but few hypothalamic sleep-promoting signaling pathways have been identified. Here we demonstrate a role for the neuropeptide QRFP (also known as P518 and 26RFa) and its receptors in regulating sleep in zebrafish, a diurnal vertebrate. We show that QRFP is expressed in ~10 hypothalamic neurons in zebrafish larvae, which project to the hypothalamus, hindbrain, and spinal cord, including regions that express the two zebrafish QRFP receptor paralogs. We find that the overexpression of QRFP inhibits locomotor activity during the day, whereas mutation of qrfp or its receptors results in increased locomotor activity and decreased sleep during the day. Despite the restriction of these phenotypes to the day, the circadian clock does not regulate qrfp expression, and entrained circadian rhythms are not required for QRFP-induced rest. Instead, we find that QRFP overexpression decreases locomotor activity largely in a light-specific manner. Our results suggest that QRFP signaling plays an important role in promoting sleep and may underlie some aspects of hypothalamic sleep control. SIGNIFICANCE STATEMENT: The hypothalamus is thought to play a key role in regulating sleep in vertebrate animals, but few sleep-promoting signaling pathways that function in the hypothalamus have been identified. Here we use the zebrafish, a diurnal vertebrate, to functionally and anatomically characterize the neuropeptide QRFP. We show that QRFP is exclusively expressed in a small number of neurons in the larval zebrafish hypothalamus that project widely in the brain. We also show that QRFP overexpression reduces locomotor activity, whereas animals that lack QRFP signaling are more active and sleep less. These results suggest that QRFP signaling participates in the hypothalamic regulation of sleep. PMID- 26865609 TI - Interdigitated Color- and Disparity-Selective Columns within Human Visual Cortical Areas V2 and V3. AB - In nonhuman primates (NHPs), secondary visual cortex (V2) is composed of repeating columnar stripes, which are evident in histological variations of cytochrome oxidase (CO) levels. Distinctive "thin" and "thick" stripes of dark CO staining reportedly respond selectively to stimulus variations in color and binocular disparity, respectively. Here, we first tested whether similar color selective or disparity-selective stripes exist in human V2. If so, available evidence predicts that such stripes should (1) radiate "outward" from the V1-V2 border, (2) interdigitate, (3) differ from each other in both thickness and length, (4) be spaced ~3.5-4 mm apart (center-to-center), and, perhaps, (5) have segregated functional connections. Second, we tested whether analogous segregated columns exist in a "next-higher" tier area, V3. To answer these questions, we used high-resolution fMRI (1 * 1 * 1 mm(3)) at high field (7 T), presenting color selective or disparity-selective stimuli, plus extensive signal averaging across multiple scan sessions and cortical surface-based analysis. All hypotheses were confirmed. V2 stripes and V3 columns were reliably localized in all subjects. The two stripe/column types were largely interdigitated (e.g., nonoverlapping) in both V2 and V3. Color-selective stripes differed from disparity-selective stripes in both width (thickness) and length. Analysis of resting-state functional connections (eyes closed) showed a stronger correlation between functionally alike (compared with functionally unlike) stripes/columns in V2 and V3. These results revealed a fine-scale segregation of color-selective or disparity selective streams within human areas V2 and V3. Together with prior evidence from NHPs, this suggests that two parallel processing streams extend from visual subcortical regions through V1, V2, and V3. SIGNIFICANCE STATEMENT: In current textbooks and reviews, diagrams of cortical visual processing highlight two distinct neural-processing streams within the first and second cortical areas in monkeys. Two major streams consist of segregated cortical columns that are selectively activated by either color or ocular interactions. Because such cortical columns are so small, they were not revealed previously by conventional imaging techniques in humans. Here we demonstrate that such segregated columnar systems exist in humans. We find that, in humans, color versus binocular disparity columns extend one full area further, into the third visual area. Our approach can be extended to reveal and study additional types of columns in human cortex, perhaps including columns underlying more cognitive functions. PMID- 26865610 TI - Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. AB - Globoid cell leukodystrophy (GLD, Krabbe disease) is due to autosomal recessive mutations in the lysosomal enzyme galactosylceramidase (GALC). Many GLD patients develop infantile-onset of progressive neurologic deterioration and death by 2 years of age, whereas others have a later-onset, milder disease. Cord blood transplant slows disease progression much more effectively when performed presymptomatically, highlighting the importance of early diagnosis. Current diagnosis is based on reduced GALC activity, DNA sequence, and clinical examination. However, presymptomatic diagnosis is hampered by imperfect genotype GALC activity-phenotype correlations. In addition, three polymorphisms in the GALC gene are variably associated with disease mutations and have unknown effects on GALC activity and disease outcome. Here, we study mutations that cause infantile or later-onset GLD, and show that GALC activity is significantly lower in infantile versus later-onset mutants when measured in the lysosomal fraction, but not in whole-cell lysates. In parallel, infantile-onset mutant GALCs showed reduced trafficking to lysosomes and processing than later-onset mutant GALCs. Finally, the cis-polymorphisms also affected trafficking to the lysosome and processing of GALC. These differences potentially explain why the activity of different mutations appears similar in whole-cell extracts from lymphocytes, and suggest that measure of GALC activity in lysosomes may better predict the onset and severity of disease for a given GLD genotype. SIGNIFICANCE STATEMENT: Globoid cell leukodystrophy (GLD, Krabbe disease) is diagnosed by measuring galactosylceramidase (GALC) activity and DNA analysis. However, genotype and phenotype often do not correlate due to considerable clinical variability, even for the same mutation, for unknown reasons. We find that altered trafficking to the lysosome and processing of GALC correlates with GLD severity and is modulated by cis-polymorphisms. Current diagnosis of GLD is based on GALC activity of total cell lysates from blood, which does not discriminate whether the activity comes from the lysosome or other subcellular organelles. Measurement of GALC activity in lysosomes may predict which infants are at high risk for the infantile phenotype while distinguishing other children who will develop later-onset phenotypes without onset of symptoms for years. PMID- 26865611 TI - Aerobic Glycolysis in the Frontal Cortex Correlates with Memory Performance in Wild-Type Mice But Not the APP/PS1 Mouse Model of Cerebral Amyloidosis. AB - Aerobic glycolysis and lactate production in the brain plays a key role in memory, yet the role of this metabolism in the cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined the relationship between cerebral lactate levels and memory performance in an APP/PS1 mouse model of AD, which progressively accumulates amyloid-beta. In vivo (1)H magnetic resonance spectroscopy revealed an age-dependent decline in lactate levels within the frontal cortex of control mice, whereas lactate levels remained unaltered in APP/PS1 mice from 3 to 12 months of age. Analysis of hippocampal interstitial fluid by in vivo microdialysis revealed a significant elevation in lactate levels in APP/PS1 mice relative to control mice at 12 months of age. An age-dependent decline in the levels of key aerobic glycolysis enzymes and a concomitant increase in lactate transporter expression was detected in control mice. Increased expression of lactate-producing enzymes correlated with improved memory in control mice. Interestingly, in APP/PS1 mice the opposite effect was detected. In these mice, increased expression of lactate producing enzymes correlated with poorer memory performance. Immunofluorescent staining revealed localization of the aerobic glycolysis enzymes pyruvate dehydrogenase kinase and lactate dehydrogenase A within cortical and hippocampal neurons in control mice, as well as within astrocytes surrounding amyloid plaques in APP/PS1 mice. These observations collectively indicate that production of lactate, via aerobic glycolysis, is beneficial for memory function during normal aging. However, elevated lactate levels in APP/PS1 mice indicate perturbed lactate processing, a factor that may contribute to cognitive decline in AD. SIGNIFICANCE STATEMENT: Lactate has recently emerged as a key metabolite necessary for memory consolidation. Lactate is the end product of aerobic glycolysis, a unique form of metabolism that occurs within certain regions of the brain. Here we detected an age-dependent decline in the expression of aerobic glycolysis enzymes and a concomitant decrease in lactate levels within the frontal cortex of wild-type mice. Improved memory performance in wild-type mice correlated with elevated expression of aerobic glycolysis enzymes. Surprisingly, lactate levels remained elevated with age and increased aerobic glycolysis enzyme expression correlated with poorer memory performance in APP/PS1 mice. These findings suggest that while lactate production is beneficial for memory in the healthy aging brain, it might be detrimental in an Alzheimer's disease context. PMID- 26865612 TI - Opposing Roles of Cholinergic and GABAergic Activity in the Insular Cortex and Nucleus Basalis Magnocellularis during Novel Recognition and Familiar Taste Memory Retrieval. AB - Acetylcholine (ACh) is thought to facilitate cortical plasticity during memory formation and its release is regulated by the nucleus basalis magnocellularis (NBM). Questions remain regarding which neuronal circuits and neurotransmitters trigger activation or suppression of cortical cholinergic activity. During novel, but not familiar, taste consumption, there is a significant increase in ACh release in the insular cortex (IC), a highly relevant structure for taste learning. Here, we evaluate how GABA inhibition modulates cholinergic transmission and its involvement during taste novelty processing and familiar taste memory retrieval. Using saccharin as a taste stimulus in a taste preference paradigm, we examined the effects of injecting the GABAA receptor agonist muscimol or the GABAA receptor antagonist bicuculline into the IC or NBM during learning or retrieval of an appetitive taste memory on taste preference in male Sprague Dawley rats. GABAA receptor agonism and antagonism had opposite effects on cortical ACh levels in novel taste presentation versus familiar taste recognition and ACh levels were associated with the propensity to acquire or retrieve a taste memory. These results indicate that the pattern of cortical cholinergic and GABAergic neuroactivity during novel taste exposure is the opposite of that which occurs during familiar taste recognition and these differing neurotransmitter system states may enable different behavioral consequences. Divergences in ACh and GABA levels may produce differential alterations in excitatory and inhibitory neural processes within the cortex during acquisition and retrieval. SIGNIFICANCE STATEMENT: During learning and recall, several brain structures act together. This work demonstrates interactions between cortical cholinergic and GABAergic systems during taste learning and memory retrieval. We found that the neuroactivity pattern during novel taste exposure is opposite that which occurs during familiar taste recognition. GABAA receptors must be inactive during novel tasting to enable new memory formation, but must be active and inhibiting acetylcholine release in the cortex to allow memory retrieval. These findings indicate that GABA inhibition modulates cholinergic transmission and that cholinergic-GABAergic system interactions are important during the transition from novel to familiar memory. PMID- 26865613 TI - Cell-Surface and Secreted Isoforms of CSF-1 Exert Opposing Roles in Macrophage Mediated Neural Damage in Cx32-Deficient Mice. AB - Previous studies in myelin-mutant mouse models of the inherited and incurable nerve disorder, Charcot-Marie-Tooth (CMT) neuropathy, have demonstrated that low grade secondary inflammation implicating phagocytosing macrophages amplifies demyelination, Schwann cell dedifferentiation and perturbation of axons. The cytokine colony stimulating factor-1 (CSF-1) acts as an important regulator of these macrophage-related disease mechanisms, as genetic and pharmacologic approaches to block the CSF-1/CSF-1R signaling result in a significant alleviation of pathological alterations in mutant peripheral nerves. In mouse models of CMT1A and CMT1X, as well as in human biopsies, CSF-1 is predominantly expressed by endoneurial fibroblasts, which are closely associated with macrophages, suggesting local stimulatory mechanisms. Here we investigated the impact of cell-surface and secreted isoforms of CSF-1 on macrophage-related disease in connexin32-deficient (Cx32def) mice, a mouse model of CMT1X. Our present observations suggest that the secreted proteoglycan isoform (spCSF-1) is predominantly expressed by fibroblasts, whereas the membrane-spanning cell surface isoform (csCSF-1) is expressed by macrophages. Using crossbreeding approaches to selectively restore or overexpress distinct isoforms in CSF-1 deficient (osteopetrotic) Cx32def mice, we demonstrate that both isoforms equally regulate macrophage numbers dose-dependently. However, spCSF-1 mediates macrophage activation and macrophage-related neural damage, whereas csCSF-1 inhibits macrophage activation and attenuates neuropathy. These results further corroborate the important role of secondary inflammation in mouse models of CMT1 and might identify specific targets for therapeutic approaches to modulate innate immune reactions. SIGNIFICANCE STATEMENT: Mouse models of Charcot-Marie-Tooth neuropathy have indicated that low-grade secondary inflammation involving phagocytosing macrophages amplifies demyelination, Schwann cell dedifferentiation, and perturbation of axons. The recruitment and pathogenic activation of detrimental macrophages is regulated by CSF-1, a cytokine that is mostly expressed by fibroblasts in the diseased nerve and exists in three isoforms. We show that the cell-surface and secreted isoforms of CSF-1 have opposing effects on macrophage activation and disease progression in a mouse model of CMT1X. These insights into opposing functions of disease-modulating cytokine isoforms might enable the development of specific therapeutic approaches. PMID- 26865615 TI - Shawn, the Drosophila Homolog of SLC25A39/40, Is a Mitochondrial Carrier That Promotes Neuronal Survival. AB - Mitochondria play an important role in the regulation of neurotransmission, and mitochondrial impairment is a key event in neurodegeneration. Cells rely on mitochondrial carrier proteins of the SLC25 family to shuttle ions, cofactors, and metabolites necessary for enzymatic reactions. Mutations in these carriers often result in rare but severe pathologies in the brain, and some of the genes, including SLC25A39 and SLC25A40, reside in susceptibility loci of severe forms of epilepsy. However, the role of most of these carriers has not been investigated in neurons in vivo. We identified shawn, the Drosophila homolog of SLC25A39 and SLC25A40, in a genetic screen to identify genes involved in neuronal function. Shawn localizes to mitochondria, and missense mutations result in an accumulation of reactive oxygen species, mitochondrial dysfunction, and neurodegeneration. Shawn regulates metal homeostasis, and we found in shawn mutants increased levels of manganese, calcium, and mitochondrial free iron. Mitochondrial mutants often cannot maintain synaptic transmission under demanding conditions, but shawn mutants do, and they also do not display endocytic defects. In contrast, shawn mutants harbor a significant increase in neurotransmitter release. Our work provides the first functional annotation of these essential mitochondrial carriers in the nervous system, and the results suggest that metal imbalances and mitochondrial dysfunction may contribute to defects in synaptic transmission and neuronal survival. SIGNIFICANCE STATEMENT: We describe for the first time the role of the mitochondrial carrier Shawn/SLC25A39/SLC25A40 in the nervous system. In humans, these genes reside in susceptibility loci for epilepsy, and, in flies, we observe neuronal defects related to mitochondrial dysfunction and metal homeostasis defects. Interestingly, shawn mutants also harbor increased neurotransmitter release and neurodegeneration. Our data suggest a connection between maintaining a correct metal balance and mitochondrial function to regulate neuronal survival and neurotransmitter release. PMID- 26865614 TI - Temporal Asymmetry in Dark-Bright Processing Initiates Propagating Activity across Primary Visual Cortex. AB - Differences between visual pathways representing darks and lights have been shown to affect spatial resolution and detection timing. Both psychophysical and physiological studies suggest an underlying retinal origin with amplification in primary visual cortex (V1). Here we show that temporal asymmetries in the processing of darks and lights create motion in terms of propagating activity across V1. Exploiting the high spatiotemporal resolution of voltage-sensitive dye imaging, we captured population responses to abrupt local changes of luminance in cat V1. For stimulation we used two neighboring small squares presented on either bright or dark backgrounds. When a single square changed from dark to bright or vice versa, we found coherent population activity emerging at the respective retinal input locations. However, faster rising and decay times were obtained for the bright to dark than the dark to bright changes. When the two squares changed luminance simultaneously in opposite polarities, we detected a propagating wave front of activity that originated at the cortical location representing the darkened square and rapidly expanded toward the region representing the brightened location. Thus, simultaneous input led to sequential activation across cortical retinotopy. Importantly, this effect was independent of the squares' contrast with the background. We suggest imbalance in dark-bright processing as a driving force in the generation of wave-like activity. Such propagation may convey motion signals and influence perception of shape whenever abrupt shifts in visual objects or gaze cause counterchange of luminance at high-contrast borders. SIGNIFICANCE STATEMENT: An elementary process in vision is the detection of darks and lights through the retina via ON and OFF channels. Psychophysical and physiological studies suggest that differences between these channels affect spatial resolution and detection thresholds. Here we show that temporal asymmetries in the processing of darks and lights create motion signals across visual cortex. Using two neighboring squares, which simultaneously counterchanged luminance, we discovered propagating activity that was strictly drawn out from cortical regions representing the darkened location. Thus, a synchronous stimulus event translated into sequential wave-like brain activation. Such propagation may convey motion signals accessible in higher brain areas, whenever abrupt shifts in visual objects or gaze cause counterchange of luminance at high-contrast borders. PMID- 26865616 TI - Abeta40 Reduces P-Glycoprotein at the Blood-Brain Barrier through the Ubiquitin Proteasome Pathway. AB - Failure to clear amyloid-beta (Abeta) from the brain is in part responsible for Abeta brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Abeta across the blood-brain barrier is the efflux transporter P glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood-brain barrier in AD, which has been shown to be associated with Abeta brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We exposed isolated rat brain capillaries to 100 nm Abeta40, Abeta40, aggregated Abeta40, and Abeta42. We observed that only Abeta40 triggered reduction of P-gp protein expression and transport activity levels; this occurred in a dose- and time-dependent manner. To identify the steps involved in Abeta-mediated P-gp reduction, we inhibited protein ubiquitination, protein trafficking, and the ubiquitin-proteasome system, and monitored P-gp protein expression, transport activity, and P-gp-ubiquitin levels. Thus, exposing brain capillaries to Abeta40 triggers ubiquitination, internalization, and proteasomal degradation of P-gp. These findings may provide potential therapeutic targets within the blood-brain barrier to limit P-gp degradation in AD and improve Abeta brain clearance. SIGNIFICANCE STATEMENT: The mechanism reducing blood-brain barrier P-glycoprotein (P-gp) in Alzheimer's disease is poorly understood. In the present study, we focused on defining this mechanism. We demonstrate that Abeta40 drives P-gp ubiquitination, internalization, and proteasome-dependent degradation, reducing P gp protein expression and transport activity in isolated brain capillaries. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit P-gp degradation in Alzheimer's disease and improve Abeta brain clearance. PMID- 26865618 TI - Frontostriatal White Matter Integrity Predicts Development of Delay of Gratification: A Longitudinal Study. AB - The ability to delay gratification increases considerably across development. Here, we test the hypothesis that this impulse control capacity is driven by increased maturation of frontostriatal circuitry using a fiber-tracking approach combined with longitudinal imaging. In total, 192 healthy volunteers between 8 and 26 years underwent diffusion tensor imaging scanning and completed a delay discounting task twice, separated by a 2-year interval. We investigated dynamic associations between frontostriatal white matter (WM) integrity and delay of gratification skills. Moreover, we examined the predictive value of frontostriatal WM integrity for future delay of gratification skills. Results showed that delay discounting increases with age in a quadratic fashion, with greatest patience during late adolescence. Data also indicated nonlinear development of frontostriatal WM, with relative fast development during childhood and early adulthood and--on average--little change during mid-adolescence. Furthermore, the positive association between age and delay discounting was further increased in individuals with higher WM integrity of the frontostriatal tracts. Predictive analysis showed that frontostriatal WM development explained unique variance in current and future delay of gratification skills. This study adds to a descriptive relation between WM integrity and delay of gratification by showing that maturation of frontostriatal connectivity predicts changes in delay of gratification skills. These findings have implications for studies examining deviances in impulse control by showing that the developmental path between striatum and prefrontal cortex may be an important predictor for when development goes astray. SIGNIFICANCE STATEMENT: During the transition from childhood to adulthood, individuals generally show increased patience and become better in delaying gratification. The exact neural correlates of delay of gratification, however, remain poorly understood. By measuring both frontostriatal white matter (WM) integrity and delay of gratification skills at two time points, we were able to provide links for our understanding of the neural mechanisms underlying this type of impulse regulation capacity. We demonstrate that the ability to delay gratification improves between childhood and young adulthood and this improvement is predicted by the integrity of frontostriatal WM connections. This study adds to a descriptive relation between WM quality and delay of gratification by showing that maturation of frontostriatal connectivity predicts improvements in delay of gratification skills. PMID- 26865617 TI - Amiloride-Insensitive Salt Taste Is Mediated by Two Populations of Type III Taste Cells with Distinct Transduction Mechanisms. AB - Responses in the amiloride-insensitive (AI) pathway, one of the two pathways mediating salty taste in mammals, are modulated by the size of the anion of a salt. This "anion effect" has been hypothesized to result from inhibitory transepithelial potentials (TPs) generated across the lingual epithelium as cations permeate through tight junctions and leave their larger and less permeable anions behind (Ye et al., 1991). We tested directly the necessity of TPs for the anion effect by measuring responses to NaCl and Na-gluconate (small and large anion sodium salts, respectively) in isolated taste cells from mouse circumvallate papillae. Using calcium imaging, we identified AI salt-responsive type III taste cells and demonstrated that they compose a subpopulation of acid responsive taste cells. Even in the absence of TPs, many (66%) AI salt-responsive type III taste cells still exhibited the anion effect, demonstrating that some component of the transduction machinery for salty taste in type III cells is sensitive to anion size. We hypothesized that osmotic responses could explain why a minority of type III cells (34%) had AI salt responses but lacked anion sensitivity. All AI type III cells had osmotic responses to cellobiose, which were significantly modulated by extracellular sodium concentration, suggesting the presence of a sodium-conducting osmotically sensitive ion channel. However, these responses were significantly larger in AI type III cells that did not exhibit the anion effect. These findings indicate that multiple mechanisms could underlie AI salt responses in type III taste cells, one of which may contribute to the anion effect. SIGNIFICANCE STATEMENT: Understanding the mechanisms underlying salty taste will help inform strategies to combat the health problems associated with NaCl overconsumption by humans. Of the two pathways underlying salty taste in mammals, the amiloride-insensitive (AI) pathway is the least understood. Using calcium imaging of isolated mouse taste cells, we identify two separate populations of AI salt-responsive type III taste cells distinguished by their sensitivity to anion size and show that these cells compose subpopulations of acid-responsive taste cells. We also find evidence that a sodium-conducting osmotically sensitive mechanism contributes to salt responses in type III taste cells. Our data not only provide new insights into the transduction mechanisms of AI salt taste but also have important implications for general theories of taste encoding. PMID- 26865619 TI - beta-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly. AB - The accumulation of beta-amyloid (Abeta) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Abeta deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Abeta deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed (18)F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Abeta+) or negative (Abeta-). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Abeta-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Abeta+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Abeta deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression. SIGNIFICANCE STATEMENT: The accumulation of beta-amyloid (Abeta) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Abeta deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Abeta-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Abeta-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Abeta deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Abeta pathology. PMID- 26865620 TI - Inactivation of the Dorsal Premotor Area Disrupts Internally Generated, But Not Visually Guided, Sequential Movements. AB - As skill on a sequence of movements is acquired through practice, each movement in the sequence becomes seamlessly associated with another. To study the neural basis of acquired skills, we trained two monkeys (Cebus apella) to perform two sequential reaching tasks. In one task, sequential movements were instructed by visual cues, whereas in the other task, movements were generated from memory after extended practice. Then, we examined neural activity in the dorsal premotor area (PMd) and the effects of its local inactivation during performance of each task. Comparable numbers of neurons in the PMd were active during the two tasks. However, inactivation of the PMd had a marked effect only on the performance of sequential movements that were guided by memory. These results emphasize the importance of the PMd in the internal generation of sequential movements, perhaps through maintaining arbitrary motor-motor associations. SIGNIFICANCE STATEMENT: The dorsal premotor cortex (PMd) has long been thought to be a critical node in the cortical networks responsible for visually guided reaching. Here we show that PMd neurons are active during both visually guided and internally generated sequential movements. In addition, we found that local inactivation of the PMd has a marked effect only on the performance of sequential movements that were internally generated. These observations suggest that, although the PMd may participate in the generation of visually guided sequences, it is more important for the generation of internally guided sequences. PMID- 26865622 TI - Multifaceted Contributions by Different Regions of the Orbitofrontal and Medial Prefrontal Cortex to Probabilistic Reversal Learning. AB - Different subregions of the prefrontal cortex (PFC) contribute to the ability to respond flexibly to changes in reward contingencies, with the medial versus orbitofrontal cortex (OFC) subregions contributing differentially to processes such as set-shifting and reversal learning. To date, the manner in which these regions may facilitate reversal learning in situations involving reward uncertainty remains relatively unexplored. We investigated the involvement of five distinct regions of the rat OFC (lateral and medial) and medial PFC (prelimbic, infralimbic, and anterior cingulate) on probabilistic reversal learning wherein "correct" versus "incorrect" responses were rewarded on 80% and 20% of trials, respectively. Contingencies were reversed repeatedly within a session. In well trained rats, inactivation of the medial or lateral OFC induced dissociable impairments in performance (indexed by fewer reversals completed) when outcomes were probabilistic, but not when they were assured. Medial OFC inactivation impaired probabilistic learning during the first discrimination, increased perseverative responding and reduced sensitivity to positive and negative feedback, suggestive of a deficit in incorporating information about previous action outcomes to guide subsequent behavior. Lateral OFC inactivation preferentially impaired performance during reversal phases. In contrast, prelimbic inactivation caused an apparent improvement in performance by increasing the number of reversals completed. This was associated with enhanced sensitivity to recently rewarded actions and reduced sensitivity to negative feedback. Infralimbic inactivation had no effect, whereas the anterior cingulate appeared to play a permissive role in this form of reversal learning. These results clarify the dissociable contributions of different regions of the frontal lobes to probabilistic learning. SIGNIFICANCE STATEMENT: The ability to adjust behavior in response to changes involving uncertain or probabilistic reward contingencies is an essential survival skill that is impaired in a variety of psychiatric disorders. It is well established that different forms of cognitive flexibility are mediated by anatomically distinct regions of the frontal lobes when reinforcement contingencies are assured, however, less is known about the contribution of these regions to probabilistic reinforcement learning. Here we show that different regions of the orbitofrontal and medial prefrontal cortex make distinct contributions to probabilistic reversal learning. These findings provide novel information about the complex interplay between frontal lobe regions in mediating these processes and accordingly provide insight into possible pathophysiology that underlies impairments in cognitive flexibility observed in mental illnesses. PMID- 26865621 TI - Mind the Gap: Two Dissociable Mechanisms of Temporal Processing in the Auditory System. AB - High temporal acuity of auditory processing underlies perception of speech and other rapidly varying sounds. A common measure of auditory temporal acuity in humans is the threshold for detection of brief gaps in noise. Gap-detection deficits, observed in developmental disorders, are considered evidence for "sluggish" auditory processing. Here we show, in a mouse model of gap-detection deficits, that auditory brain sensitivity to brief gaps in noise can be impaired even without a general loss of central auditory temporal acuity. Extracellular recordings in three different subdivisions of the auditory thalamus in anesthetized mice revealed a stimulus-specific, subdivision-specific deficit in thalamic sensitivity to brief gaps in noise in experimental animals relative to controls. Neural responses to brief gaps in noise were reduced, but responses to other rapidly changing stimuli unaffected, in lemniscal and nonlemniscal (but not polysensory) subdivisions of the medial geniculate body. Through experiments and modeling, we demonstrate that the observed deficits in thalamic sensitivity to brief gaps in noise arise from reduced neural population activity following noise offsets, but not onsets. These results reveal dissociable sound-onset-sensitive and sound-offset-sensitive channels underlying auditory temporal processing, and suggest that gap-detection deficits can arise from specific impairment of the sound-offset-sensitive channel. SIGNIFICANCE STATEMENT: The experimental and modeling results reported here suggest a new hypothesis regarding the mechanisms of temporal processing in the auditory system. Using a mouse model of auditory temporal processing deficits, we demonstrate the existence of specific abnormalities in auditory thalamic activity following sound offsets, but not sound onsets. These results reveal dissociable sound-onset-sensitive and sound offset-sensitive mechanisms underlying auditory processing of temporally varying sounds. Furthermore, the findings suggest that auditory temporal processing deficits, such as impairments in gap-in-noise detection, could arise from reduced brain sensitivity to sound offsets alone. PMID- 26865623 TI - miR-124 Regulates the Phase of Drosophila Circadian Locomotor Behavior. AB - Animals use circadian rhythms to anticipate daily environmental changes. Circadian clocks have a profound effect on behavior. In Drosophila, for example, brain pacemaker neurons dictate that flies are mostly active at dawn and dusk. miRNAs are small, regulatory RNAs (~22 nt) that play important roles in posttranscriptional regulation. Here, we identify miR-124 as an important regulator of Drosophila circadian locomotor rhythms. Under constant darkness, flies lacking miR-124 (miR-124(KO)) have a dramatically advanced circadian behavior phase. However, whereas a phase defect is usually caused by a change in the period of the circadian pacemaker, this is not the case in miR-124(KO) flies. Moreover, the phase of the circadian pacemaker in the clock neurons that control rhythmic locomotion is not altered either. Therefore, miR-124 modulates the output of circadian clock neurons rather than controlling their molecular pacemaker. Circadian phase is also advanced under temperature cycles, but a light/dark cycle partially corrects the defects in miR-124(KO) flies. Indeed, miR 124(KO) shows a normal evening phase under the latter conditions, but morning behavioral activity is suppressed. In summary, miR-124 controls diurnal activity and determines the phase of circadian locomotor behavior without affecting circadian pacemaker function. It thus provides a potent entry point to elucidate the mechanisms by which the phase of circadian behavior is determined. SIGNIFICANCE STATEMENT: In animals, molecular circadian clocks control the timing of behavioral activities to optimize them with the day/night cycle. This is critical for their fitness and survival. The mechanisms by which the phase of circadian behaviors is determined downstream of the molecular pacemakers are not yet well understood. Recent studies indicate that miRNAs are important regulators of circadian outputs. We found that miR-124 shapes diurnal behavioral activity and has a striking impact on the phase of circadian locomotor behavior. Surprisingly, the period and phase of the neural circadian pacemakers driving locomotor rhythms are unaffected. Therefore, miR-124 is a critical modulator of the circadian output pathways that control circadian behavioral rhythms. PMID- 26865625 TI - Astrocytic GAP43 Induced by the TLR4/NF-kappaB/STAT3 Axis Attenuates Astrogliosis Mediated Microglial Activation and Neurotoxicity. AB - Growth-associated protein 43 (GAP43), a protein kinase C (PKC)-activated phosphoprotein, is often implicated in axonal plasticity and regeneration. In this study, we found that GAP43 can be induced by the endotoxin lipopolysaccharide (LPS) in rat brain astrocytes both in vivo and in vitro. The LPS-induced astrocytic GAP43 expression was mediated by Toll-like receptor 4 and nuclear factor-kappaB (NF-kappaB)- and interleukin-6/signal transducer and activator of transcription 3 (STAT3)-dependent transcriptional activation. The overexpression of the PKC phosphorylation-mimicking GAP43(S41D) (constitutive active GAP43) in astrocytes mimicked LPS-induced process arborization and elongation, while application of a NF-kappaB inhibitory peptide TAT-NBD or GAP43(S41A) (dominant-negative GAP43) or knockdown of GAP43 all inhibited astrogliosis responses. Moreover, GAP43 knockdown aggravated astrogliosis-induced microglial activation and expression of proinflammatory cytokines. We also show that astrogliosis-conditioned medium from GAP43 knock-down astrocytes inhibited GAP43 phosphorylation and axonal growth, and increased neuronal damage in cultured rat cortical neurons. These proneurotoxic effects of astrocytic GAP43 knockdown were accompanied by attenuated glutamate uptake and expression of the glutamate transporter excitatory amino acid transporter 2 (EAAT2) in LPS-treated astrocytes. The regulation of EAAT2 expression involves actin polymerization dependent activation of the transcriptional coactivator megakaryoblastic leukemia 1 (MKL1), which targets the serum response elements in the promoter of rat Slc1a2 gene encoding EAAT2. In sum, the present study suggests that astrocytic GAP43 mediates glial plasticity during astrogliosis, and provides beneficial effects for neuronal plasticity and survival and attenuation of microglial activation. SIGNIFICANCE STATEMENT: Astrogliosis is a complex state in which injury stimulated astrocytes exert both protective and harmful effects on neuronal survival and plasticity. In this study, we demonstrated for the first time that growth-associated protein 43 (GAP43), a well known growth cone protein that promotes axonal regeneration, can be induced in rat brain astrocytes by the proinflammatory endotoxin lipopolysaccharide via both nuclear factor-kappaB and signal transducer and activator of transcription 3-mediated transcriptional activation. Importantly, LPS-induced GAP43 mediates plastic changes of astrocytes while attenuating astrogliosis-induced microglial activation and neurotoxicity. Hence, astrocytic GAP43 upregulation may serve to indicate beneficial astrogliosis after CNS injury. PMID- 26865626 TI - Evidence That the Laminar Fate of LGE/CGE-Derived Neocortical Interneurons Is Dependent on Their Progenitor Domains. AB - Neocortical interneurons show tremendous diversity in terms of their neurochemical marker expressions, morphology, electrophysiological properties, and laminar fate. Allocation of interneurons to their appropriate regions and layers in the neocortex is thought to play important roles for the emergence of higher functions of the neocortex. Neocortical interneurons mainly originate from the medial ganglionic eminence (MGE) and the caudal ganglionic eminence (CGE). The diversity and the laminar fate of MGE-derived interneurons depend on the location of their birth and birthdate, respectively. However, this relationship does not hold for CGE-derived interneurons. Here, using the method of in utero electroporation, which causes arbitrary occurrence of labeled progenitor domains, we tracked all descendants of the lateral ganglionic eminence (LGE)/CGE progenitors in mice. We provide evidence that neocortical interneurons with distinct laminar fate originate from distinct progenitor domains within the LGE/CGE. We find layer I interneurons are predominantly labeled in a set of animals, whereas other upper layer neurons are predominantly labeled in another set. We also find distinct subcortical structures labeled between the two sets. Further, interneurons labeled in layer I show distinct neurochemical properties from those in other layers. Together, these results suggest that the laminar fate of LGE/CGE-derived interneurons depends on their spatial origin. SIGNIFICANCE STATEMENT: Diverse types of neocortical interneurons have distinct laminar fate, neurochemical marker expression, morphology, and electrophysiological properties. Although the specifications and laminar fate of medial ganglionic eminence derived neocortical interneurons depend on their location of embryonic origin and birthdate, no similar causality of lateral/caudal ganglionic eminence (LGE/CGE) derived neocortical interneurons is known. Here, we performed in utero electroporation on mouse LGE/CGE and found two groups of animals, one with preferential labeling of layer I and the other with preferential labeling of other layers. Interneurons labeled in these two groups show distinct neurochemical properties and morphologies and are associated with labeling of distinct subcortical structures. These findings suggest that the laminar fate of LGE/CGE-derived neocortical interneurons depends on their spatial origin. PMID- 26865624 TI - Human Superior Temporal Gyrus Organization of Spectrotemporal Modulation Tuning Derived from Speech Stimuli. AB - The human superior temporal gyrus (STG) is critical for speech perception, yet the organization of spectrotemporal processing of speech within the STG is not well understood. Here, to characterize the spatial organization of spectrotemporal processing of speech across human STG, we use high-density cortical surface field potential recordings while participants listened to natural continuous speech. While synthetic broad-band stimuli did not yield sustained activation of the STG, spectrotemporal receptive fields could be reconstructed from vigorous responses to speech stimuli. We find that the human STG displays a robust anterior-posterior spatial distribution of spectrotemporal tuning in which the posterior STG is tuned for temporally fast varying speech sounds that have relatively constant energy across the frequency axis (low spectral modulation) while the anterior STG is tuned for temporally slow varying speech sounds that have a high degree of spectral variation across the frequency axis (high spectral modulation). This work illustrates organization of spectrotemporal processing in the human STG, and illuminates processing of ethologically relevant speech signals in a region of the brain specialized for speech perception. SIGNIFICANCE STATEMENT: Considerable evidence has implicated the human superior temporal gyrus (STG) in speech processing. However, the gross organization of spectrotemporal processing of speech within the STG is not well characterized. Here we use natural speech stimuli and advanced receptive field characterization methods to show that spectrotemporal features within speech are well organized along the posterior-to-anterior axis of the human STG. These findings demonstrate robust functional organization based on spectrotemporal modulation content, and illustrate that much of the encoded information in the STG represents the physical acoustic properties of speech stimuli. PMID- 26865627 TI - Cholinergic Neurons in the Basal Forebrain Promote Wakefulness by Actions on Neighboring Non-Cholinergic Neurons: An Opto-Dialysis Study. AB - Understanding the control of sleep-wake states by the basal forebrain (BF) poses a challenge due to the intermingled presence of cholinergic, GABAergic, and glutamatergic neurons. All three BF neuronal subtypes project to the cortex and are implicated in cortical arousal and sleep-wake control. Thus, nonspecific stimulation or inhibition studies do not reveal the roles of these different neuronal types. Recent studies using optogenetics have shown that "selective" stimulation of BF cholinergic neurons increases transitions between NREM sleep and wakefulness, implicating cholinergic projections to cortex in wake promotion. However, the interpretation of these optogenetic experiments is complicated by interactions that may occur within the BF. For instance, a recent in vitro study from our group found that cholinergic neurons strongly excite neighboring GABAergic neurons, including the subset of cortically projecting neurons, which contain the calcium-binding protein, parvalbumin (PV) (Yang et al., 2014). Thus, the wake-promoting effect of "selective" optogenetic stimulation of BF cholinergic neurons could be mediated by local excitation of GABA/PV or other non cholinergic BF neurons. In this study, using a newly designed opto-dialysis probe to couple selective optical stimulation with simultaneous in vivo microdialysis, we demonstrated that optical stimulation of cholinergic neurons locally increased acetylcholine levels and increased wakefulness in mice. Surprisingly, the enhanced wakefulness caused by cholinergic stimulation was abolished by simultaneous reverse microdialysis of cholinergic receptor antagonists into BF. Thus, our data suggest that the wake-promoting effect of cholinergic stimulation requires local release of acetylcholine in the basal forebrain and activation of cortically projecting, non-cholinergic neurons, including the GABAergic/PV neurons. SIGNIFICANCE STATEMENT: Optogenetics is a revolutionary tool to assess the roles of particular groups of neurons in behavioral functions, such as control of sleep and wakefulness. However, the interpretation of optogenetic experiments requires knowledge of the effects of stimulation on local neurotransmitter levels and effects on neighboring neurons. Here, using a novel "opto-dialysis" probe to couple optogenetics and in vivo microdialysis, we report that optical stimulation of basal forebrain (BF) cholinergic neurons in mice increases local acetylcholine levels and wakefulness. Reverse microdialysis of cholinergic antagonists within BF prevents the wake-promoting effect. This important result challenges the prevailing dictum that BF cholinergic projections to cortex directly control wakefulness and illustrates the utility of "opto dialysis" for dissecting the complex brain circuitry underlying behavior. PMID- 26865628 TI - Increased Synchrony and Bursting of Dorsal Cochlear Nucleus Fusiform Cells Correlate with Tinnitus. AB - Tinnitus, the perception of phantom sounds, is thought to arise from increased neural synchrony, which facilitates perceptual binding and creates salient sensory features in the absence of physical stimuli. In the auditory cortex, increased spontaneous cross-unit synchrony and single-unit bursting are de facto physiological correlates of tinnitus. However, it is unknown whether neurons in the dorsal cochlear nucleus (DCN), the putative tinnitus-induction site, exhibit increased synchrony. Using a temporary-threshold shift model and gap-prepulse inhibition of the acoustic startle to assess tinnitus, we recorded spontaneous activity from fusiform cells, the principle neurons of the DCN, in normal hearing, tinnitus, and non-tinnitus guinea pigs. Synchrony and bursting, as well as spontaneous firing rate (SFR), correlated with behavioral evidence of tinnitus, and increased synchrony and bursting were associated with SFR elevation. The presence of increased synchrony and bursting in DCN fusiform cells suggests that a neural code for phantom sounds emerges in this brainstem location and likely contributes to the formation of the tinnitus percept. SIGNIFICANCE STATEMENT: Tinnitus, a phantom auditory percept, is encoded by pathological changes in the neural synchrony code of perceptual processing. Increased cross unit synchrony and bursting have been linked to tinnitus in several higher auditory stations but not in fusiform cells of the dorsal cochlear nucleus (DCN), key brainstem neurons in tinnitus generation. Here, we demonstrate increased synchrony and bursting of fusiform cell spontaneous firing, which correlate with frequency-specific behavioral measures of tinnitus. Thus, the neural representation of tinnitus emerges early in auditory processing and likely drives its pathophysiology in higher structures. PMID- 26865629 TI - Human Neuropeptide S Receptor Is Activated via a Galphaq Protein-biased Signaling Cascade by a Human Neuropeptide S Analog Lacking the C-terminal 10 Residues. AB - Human neuropeptide S (NPS) and its cognate receptor regulate important biological functions in the brain and have emerged as a future therapeutic target for treatment of a variety of neurological and psychiatric diseases. The human NPS (hNPS) receptor has been shown to dually couple to Galphas- and Galphaq-dependent signaling pathways. The human NPS analog hNPS-(1-10), lacking 10 residues from the C terminus, has been shown to stimulate Ca(2+)mobilization in a manner comparable with full-length hNPSin vitrobut seems to fail to induce biological activityin vivo Here, results derived from a number of cell-based functional assays, including intracellular cAMP-response element (CRE)-driven luciferase activity, Ca(2+)mobilization, and ERK1/2 phosphorylation, show that hNPS-(1-10) preferentially activates Galphaq-dependent Ca(2+)mobilization while exhibiting less activity in triggering Galphas-dependent CRE-driven luciferase activity. We further demonstrate that both Galphaq- and Galphas-coupled signaling pathways contribute to full-length hNPS-mediated activation of ERK1/2, whereas hNPS-(1-10) promoted ERK1/2 activation is completely inhibited by the Galphaqinhibitor UBO QIC but not by the PKA inhibitor H89. Moreover, the results of Ala-scanning mutagenesis of hNPS-(1-13) indicated that residues Lys(11)and Lys(12)are structurally crucial for the hNPS receptor to couple to Galphas-dependent signaling. In conclusion, our findings demonstrate that hNPS-(1-10) is a biased agonist favoring Galphaq-dependent signaling. It may represent a valuable chemical probe for further investigation of the therapeutic potential of human NPS receptor-directed signalingin vivo. PMID- 26865630 TI - Distinct Activation Mechanisms of NF-kappaB Regulator Inhibitor of NF-kappaB Kinase (IKK) by Isoforms of the Cell Death Regulator Cellular FLICE-like Inhibitory Protein (cFLIP). AB - The viral FLICE-like inhibitory protein (FLIP) protein from Kaposi sarcoma associated herpesvirus activates the NF-kappaB pathway by forming a stable complex with a central region (amino acids 150-272) of the inhibitor of NF-kappaB kinase (IKK) gamma subunits, thereby activating IKK. Cellular FLIP (cFLIP) forms are also known to activate the NF-kappaB pathway via IKK activation. Here we demonstrate that cFLIPL, cFLIPS, and their proteolytic product p22-FLIP all require the C-terminal region of NEMO/IKKgamma (amino acids 272-419) and its ubiquitin binding function for activation of the IKK kinase (or kinase complex), but none form a stable complex with IKKgamma. Our results further reveal that cFLIPLrequires the linear ubiquitin chain assembly complex and the kinase TAK1 for activation of the IKK kinase. Similarly, cFLIPSand p22-FLIP also require TAK1 but do not require LUBAC. In contrast, these isoforms are both components of complexes that incorporate Fas-associated death domain and RIP1, which appear essential for kinase activation. This conservation of IKK activation among the cFLIP family using different mechanisms suggests that the mechanism plays a critical role in their function. PMID- 26865631 TI - A Highly Conserved Salt Bridge Stabilizes the Kinked Conformation of beta2,3 Sheet Essential for Channel Function of P2X4 Receptors. AB - Significant progress has been made in understanding the roles of crucial residues/motifs in the channel function of P2X receptors during the pre-structure era. The recent structural determination of P2X receptors allows us to reevaluate the role of those residues/motifs. Residues Arg-309 and Asp-85 (rat P2X4 numbering) are highly conserved throughout the P2X family and were involved in loss-of-function polymorphism in human P2X receptors. Previous studies proposed that they participated in direct ATP binding. However, the crystal structure of P2X demonstrated that those two residues form an intersubunit salt bridge located far away from the ATP-binding site. Therefore, it is necessary to reevaluate the role of this salt bridge in P2X receptors. Here, we suggest the crucial role of this structural element both in protein stability and in channel gating rather than direct ATP interaction and channel assembly. Combining mutagenesis, charge swap, and disulfide cross-linking, we revealed the stringent requirement of this salt bridge in normal P2X4 channel function. This salt bridge may contribute to stabilizing the bending conformation of the beta2,3-sheet that is structurally coupled with this salt bridge and the alpha2-helix. Strongly kinked beta2,3 is essential for domain-domain interactions between head domain, dorsal fin domain, right flipper domain, and loop beta7,8 in P2X4 receptors. Disulfide cross-linking with directions opposing or along the bending angle of the beta2,3-sheet toward the alpha2-helix led to loss-of-function and gain-of-function of P2X4 receptors, respectively. Further insertion of amino acids with bulky side chains into the linker between the beta2,3-sheet or the conformational change of the alpha2 helix, interfering with the kinked conformation of beta2,3, led to loss-of function of P2X4 receptors. All these findings provided new insights in understanding the contribution of the salt bridge between Asp-85 and Arg-309 and its structurally coupled beta2,3-sheet to the function of P2X receptors. PMID- 26865632 TI - Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress. AB - Redox fluctuations within cells can be detrimental to cell function. To gain insight into how cells normally buffer against redox changes to maintain cell function, we have focused on elucidating the signaling pathways that serve to sense and respond to oxidative redox stress within the endoplasmic reticulum (ER) using yeast as a model system. Previously, we have shown that a cysteine in the molecular chaperone BiP, a Hsp70 molecular chaperone within the ER, is susceptible to oxidation by peroxide during ER-derived oxidative stress, forming a sulfenic acid (-SOH) moiety. Here, we demonstrate that this same conserved BiP cysteine is susceptible also to glutathione modification (-SSG). Glutathionylated BiP is detected both as a consequence of enhanced levels of cellular peroxide and also as a by-product of increased levels of oxidized glutathione (GSSG). Similar to sulfenylation, we observe glutathionylation decouples BiP ATPase and peptide binding activities, turning BiP from an ATP-dependent foldase into an ATP independent holdase. We show glutathionylation enhances cell proliferation during oxidative stress, which we suggest relates to modified BiP's increased ability to limit polypeptide aggregation. We propose the susceptibility of BiP to modification with glutathione may serve also to prevent irreversible oxidation of BiP by peroxide. PMID- 26865633 TI - Regulation of Ligand and Shear Stress-induced Insulin-like Growth Factor 1 (IGF1) Signaling by the Integrin Pathway. AB - Mechanical loading of the skeleton, as achieved during daily movement and exercise, preserves bone mass and stimulates bone formation, whereas skeletal unloading from prolonged immobilization leads to bone loss. A functional interplay between the insulin-like growth factor 1 receptor (IGF1R), a major player in skeletal development, and integrins, mechanosensors, is thought to regulate the anabolic response of osteogenic cells to mechanical load. The mechanistic basis for this cross-talk is unclear. Here we report that integrin signaling regulates activation of IGF1R and downstream targets in response to both IGF1 and a mechanical stimulus. In addition, integrins potentiate responsiveness of IGF1R to IGF1 and mechanical forces. We demonstrate that integrin-associated kinases, Rous sarcoma oncogene (SRC) and focal adhesion kinase (FAK), display distinct actions on IGF1 signaling; FAK regulates IGF1R activation and its downstream effectors, AKT and ERK, whereas SRC controls signaling downstream of IGF1R. These findings linked to our observation that IGF1 assembles the formation of a heterocomplex between IGF1R and integrin beta3 subunit indicate that the regulation of IGF1 signaling by integrins proceeds by direct receptor-receptor interaction as a possible means to translate biomechanical forces into osteoanabolic signals. PMID- 26865634 TI - A Protein-derived Oxygen Is the Source of the Amide Oxygen of Nitrile Hydratases. AB - Nitrile hydratase metalloenzymes are unique and important biocatalysts that are used industrially to produce high value amides from their corresponding nitriles. After more than three decades since their discovery, the mechanism of this class of enzymes is becoming clear with evidence from multiple recent studies that the cysteine-derived sulfenato ligand of the active site metal serves as the nucleophile that initially attacks the nitrile. Herein we describe the first direct evidence from solution phase catalysis that the source of the product carboxamido oxygen is the protein. Using(18)O-labeled water under single turnover conditions and native high resolution protein mass spectrometry, we show that the incorporation of labeled oxygen into both product and protein is turnover dependent and that only a single oxygen is exchanged into the protein even under multiple turnover conditions, lending significant support to proposals that the post-translationally modified sulfenato group serves as the nucleophile to initiate hydration of nitriles. PMID- 26865635 TI - Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD) induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression. AB - Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor regulating the expression of genes involved in xenobiotic response. Recent studies have suggested that AhR plays essential roles not only in xenobiotic detoxification but also energy metabolism. Thus, in this study, we studied the roles of AhR in lipid metabolism. Under high fat diet (HFD) challenge, liver specific AhR knock-out (AhR LKO) mice exhibited severe steatosis, inflammation, and injury in the liver. Gene expression analysis and biochemical study revealed thatde novolipogenesis activity was significantly increased in AhR LKO mice. In contrast, induction of suppressor of cytokine signal 3 (Socs3) expression by HFD was attenuated in the livers of AhR LKO mice. Rescue of theSocs3gene in the liver of AhR LKO mice cancelled the HFD-induced hepatic lipotoxicities. Promoter analysis established Socs3 as novel transcriptional target of AhR. These results indicated that AhR plays a protective role against HFD-induced hepatic steatosis and the subsequent lipotoxicity effects, such as inflammation, and that the mechanism of protection involves the direct transcriptional regulation ofSocs3expression by AhR. PMID- 26865638 TI - Porsche Design's Shisha 2 hits the Lebanese market. PMID- 26865637 TI - Hexokinase 2 Is an Intracellular Glucose Sensor of Yeast Cells That Maintains the Structure and Activity of Mig1 Protein Repressor Complex. AB - Hexokinase 2 (Hxk2) fromSaccharomyces cerevisiaeis a bi-functional enzyme, being both a catalyst in the cytosol and an important regulator of the glucose repression signal in the nucleus. Despite considerable recent progress, little is known about the regulatory mechanism that controls nuclear Hxk2 association with theSUC2promoter chromatin and how this association is necessary forSUC2gene repression. Our data indicate that in theSUC2promoter context, Hxk2 functions through a variety of structurally unrelated factors, mainly the DNA-binding Mig1 and Mig2 repressors and the regulatory Snf1 and Reg1 factors. Hxk2 sustains the repressor complex architecture maintaining transcriptional repression at theSUC2gene. Using chromatin immunoprecipitation assays, we discovered that the Hxk2 in its open configuration, at low glucose conditions, leaves the repressor complex that induces its dissociation and promotesSUC2gene expression. In high glucose conditions, Hxk2 adopts a close conformation that promotes Hxk2 binding to the Mig1 protein and the reassembly of theSUC2repressor complex. Additional findings highlight the possibility that Hxk2 constitutes an intracellular glucose sensor that operates by changing its conformation in response to cytoplasmic glucose levels that regulate its interaction with Mig1 and thus its recruitment to the repressor complex of theSUC2promoter. Thus, our data indicate that Hxk2 is more intimately involved in gene regulation than previously thought. PMID- 26865639 TI - A model for chronic, intrahypothalamic thyroid hormone administration in rats. AB - In addition to the direct effects of thyroid hormone (TH) on peripheral organs, recent work showed metabolic effects of TH on the liver and brown adipose tissue via neural pathways originating in the hypothalamic paraventricular and ventromedial nucleus (PVN and VMH). So far, these experiments focused on short term administration of TH. The aim of this study is to develop a technique for chronic and nucleus-specific intrahypothalamic administration of the biologically active TH tri-iodothyronine (T3). We used beeswax pellets loaded with an amount of T3 based on in vitro experiments showing stable T3 release (~5 nmol l(-1)) for 32 days. Upon stereotactic bilateral implantation, T3 concentrations were increased 90-fold in the PVN region and 50-fold in the VMH region after placing T3-containing pellets in the rat PVN or VMH for 28 days respectively. Increased local T3 concentrations were reflected by selectively increased mRNA expression of the T3-responsive genes Dio3 and Hr in the PVN or in the VMH. After placement of T3-containing pellets in the PVN, Tshb mRNA was significantly decreased in the pituitary, without altered Trh mRNA in the PVN region. Plasma T3 and T4 concentrations decreased without altered plasma TSH. We observed no changes in pituitary Tshb mRNA, plasma TSH, or plasma TH in rats after placement of T3 containing pellets in the VMH. We developed a method to selectively and chronically deliver T3 to specific hypothalamic nuclei. This will enable future studies on the chronic effects of intrahypothalamic T3 on energy metabolism via the PVN or VMH. PMID- 26865640 TI - Angiogenesis in melanoma: an update with a focus on current targeted therapies. AB - Angiogenesis plays a crucial role in melanoma metastasis and progression. In recent years, numerous studies have investigated the prognostic and clinical significance of this phenomenon, and the development of molecular techniques has enabled us to achieve a better understanding of angiogenesis in melanoma. Herein, we review the current state of knowledge regarding angiogenesis in melanoma, including the pathophysiological, histological and immunohistochemical aspects of this phenomenon. We also review the molecular pathways involved in angiogenesis and the interplay between different components that might be manipulated in the future development of efficient targeted therapies. Recently developed targeted antiangiogenic therapies in clinical trials and included in the treatment of advanced-stage melanoma are also reviewed. PMID- 26865636 TI - Structural Insights into the Carbohydrate Binding Ability of an alpha-(1->2) Branching Sucrase from Glycoside Hydrolase Family 70. AB - The alpha-(1->2) branching sucrase DeltaN123-GBD-CD2 is a transglucosylase belonging to glycoside hydrolase family 70 (GH70) that catalyzes the transfer ofd glucosyl units from sucroseto dextrans or gluco-oligosaccharides via the formation of alpha-(1->2) glucosidic linkages. The first structures of DeltaN123 GBD-CD2 in complex withd-glucose, isomaltosyl, or isomaltotriosyl residues were solved. The glucose complex revealed three glucose-binding sites in the catalytic gorge and six additional binding sites at the surface of domains B, IV, and V. Soaking with isomaltotriose or gluco-oligosaccharides led to structures in which isomaltosyl or isomaltotriosyl residues were found in glucan binding pockets located in domain V. One aromatic residue is systematically identified at the bottom of these pockets in stacking interaction with one glucosyl moiety. The carbohydrate is also maintained by a network of hydrogen bonds and van der Waals interactions. The sequence of these binding pockets is conserved and repeatedly present in domain V of several GH70 glucansucrases known to bind alpha-glucans. These findings provide the first structural evidence of the molecular interaction occurring between isomalto-oligosaccharides and domain V of the GH70 enzymes. PMID- 26865641 TI - Brains-Computers-Machines: Neural Engineering in Science Classrooms. PMID- 26865642 TI - Examining Gender Differences in Written Assessment Tasks in Biology: A Case Study of Evolutionary Explanations. AB - Understanding sources of performance bias in science assessment provides important insights into whether science curricula and/or assessments are valid representations of student abilities. Research investigating assessment bias due to factors such as instrument structure, participant characteristics, and item types are well documented across a variety of disciplines. However, the relationships among these factors are unclear for tasks evaluating understanding through performance on scientific practices, such as explanation. Using item response theory (Rasch analysis), we evaluated differences in performance by gender on a constructed-response (CR) assessment about natural selection (ACORNS). Three isomorphic item strands of the instrument were administered to a sample of undergraduate biology majors and nonmajors (Group 1: n = 662 [female = 51.6%]; G2: n = 184 [female = 55.9%]; G3: n = 642 [female = 55.1%]). Overall, our results identify relationships between item features and performance by gender; however, the effect is small in the majority of cases, suggesting that males and females tend to incorporate similar concepts into their CR explanations. These results highlight the importance of examining gender effects on performance in written assessment tasks in biology. PMID- 26865643 TI - Increasing the Use of Student-Centered Pedagogies from Moderate to High Improves Student Learning and Attitudes about Biology. AB - Student-centered strategies are being incorporated into undergraduate classrooms in response to a call for reform. We tested whether teaching in an extensively student-centered manner (many active-learning pedagogies, consistent formative assessment, cooperative groups; the Extensive section) was more effective than teaching in a moderately student-centered manner (fewer active-learning pedagogies, less formative assessment, without groups; the Moderate section) in a large-enrollment course. One instructor taught both sections of Biology 101 during the same quarter, covering the same material. Students in the Extensive section had significantly higher mean scores on course exams. They also scored significantly higher on a content postassessment when accounting for preassessment score and student demographics. Item response theory analysis supported these results. Students in the Extensive section had greater changes in postinstruction abilities compared with students in the Moderate section. Finally, students in the Extensive section exhibited a statistically greater expert shift in their views about biology and learning biology. We suggest our results are explained by the greater number of active-learning pedagogies experienced by students in cooperative groups, the consistent use of formative assessment, and the frequent use of explicit metacognition in the Extensive section. PMID- 26865644 TI - Prenatal Choline Supplementation Diminishes Early-Life Iron Deficiency-Induced Reprogramming of Molecular Networks Associated with Behavioral Abnormalities in the Adult Rat Hippocampus. AB - BACKGROUND: Early-life iron deficiency is a common nutrient deficiency worldwide. Maternal iron deficiency increases the risk of schizophrenia and autism in the offspring. Postnatal iron deficiency in young children results in cognitive and socioemotional abnormalities in adulthood despite iron treatment. The rat model of diet-induced fetal-neonatal iron deficiency recapitulates the observed neurobehavioral deficits. OBJECTIVES: We sought to establish molecular underpinnings for the persistent psychopathologic effects of early-life iron deficiency by determining whether it permanently reprograms the hippocampal transcriptome. We also assessed the effects of maternal dietary choline supplementation on the offspring's hippocampal transcriptome to identify pathways through which choline mitigates the emergence of long-term cognitive deficits. METHODS: Male rat pups were made iron deficient (ID) by providing pregnant and nursing dams an ID diet (4 g Fe/kg) from gestational day (G) 2 through postnatal day (PND) 7 and an iron-sufficient (IS) diet (200 g Fe/kg) thereafter. Control pups were provided IS diet throughout. Choline (5 g/kg) was given to half the pregnant dams in each group from G11 to G18. PND65 hippocampal transcriptomes were assayed by next generation sequencing (NGS) and analyzed with the use of knowledge-based Ingenuity Pathway Analysis. Real-time polymerase chain reaction was performed to validate a subset of altered genes. RESULTS: Formerly ID rats had altered hippocampal expression of 619 from >10,000 gene loci sequenced by NGS, many of which map onto molecular networks implicated in psychological disorders, including anxiety, autism, and schizophrenia. There were significant interactions between iron status and prenatal choline treatment in influencing gene expression. Choline supplementation reduced the effects of iron deficiency, including those on gene networks associated with autism and schizophrenia. CONCLUSIONS: Fetal-neonatal iron deficiency reprograms molecular networks associated with the pathogenesis of neurologic and psychological disorders in adult rats. The positive response to prenatal choline represents a potential adjunctive therapeutic supplement to the high-risk group. PMID- 26865645 TI - L-Glutamine Enhances Tight Junction Integrity by Activating CaMK Kinase 2-AMP Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells. AB - BACKGROUND: The tight junctions (TJs) are essential for maintenance of the intestinal mucosal barrier integrity. Results of our recent work show that dietary l-glutamine (Gln) supplementation enhances the protein abundance of TJ proteins in the small intestine of piglets. However, the underlying mechanisms remain largely unknown. OBJECTIVE: This study was conducted to test the hypothesis that Gln regulates TJ integrity through calcium/calmodulin-dependent kinase 2 (CaMKK2)-AMP-activated protein kinase (AMPK) signaling which, in turn, contributes to improved intestinal mucosal barrier function. METHODS: Jejunal enterocytes isolated from a newborn pig were cultured in the presence of 0-2.0 mmol Gln/L for indicated time points. Cell proliferation, monolayer transepithelial electrical resistance (TEER), paracellular permeability, expression and distribution of TJ proteins, and phosphorylated AMPK were determined. RESULTS: Compared with 0 mmol Gln/L, 2.0 mmol Gln/L enhanced (P < 0.05) cell growth (by 31.9% at 48 h and 11.1% at 60 h). Cells treated with 2 mmol Gln/L increased TEER by 32.2% at 60 h, and decreased (P < 0.05) TJ permeability by 20.3-40.0% at 36-60 h. In addition, 2.0 mmol Gln/L increased (P < 0.05) the abundance of transmembrane proteins, such as occludin, claudin-4, junction adhesion molecule (JAM)-A, and the plaque proteins zonula occludens (ZO)-1, ZO-2, and ZO-3 by 1.8-6 times. In contrast, 0.5 mmol Gln/L had a moderate effect on TJ protein abundance (20.2-70.5%; P < 0.05) of occludin, claudin-3, claudin-4, JAM A, and ZO-1. 2.0 mmol Gln/L treatment led to a greater distribution of claudin-1, claudin-4, and ZO-1 at plasma membranes compared with 0 mmol Gln/L. This effect of Gln was mediated by the activation of CaMKK2-AMPK signaling, because either depletion of calcium from the medium or the presence of an inhibitor of CaMKK2 abrogated the effect of Gln on epithelial integrity. CONCLUSION: Our findings indicate that activation of CaMKK2-AMPK signaling by Gln is associated with improved intestinal mucosal barrier function through enhancing the abundance of TJ proteins and altering their intracellular localization in intestinal porcine epithelial cells. PMID- 26865647 TI - L-Citrulline Supplementation Enhances Fetal Growth and Protein Synthesis in Rats with Intrauterine Growth Restriction. AB - BACKGROUND: Intrauterine growth restriction (IUGR) results from either maternal undernutrition or impaired placental blood flow, exposing offspring to increased perinatal mortality and a higher risk of metabolic syndrome and cardiovascular disease during adulthood. l-Citrulline is a precursor of l-arginine and nitric oxide (NO), which regulates placental blood flow. Moreover, l-citrulline stimulates protein synthesis in other models of undernutrition. OBJECTIVE: The aim of the study was to determine whether l-citrulline supplementation would enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction. METHODS: Pregnant rats were fed either a control (20% protein) or a low-protein (LP; 4% protein) diet. LP dams were randomly allocated to drink tap water either as such or supplemented with l-citrulline (2 g . kg(-1) . d(-1)), an isonitrogenous amount of l-arginine, or nonessential l-amino acids (NEAAs). On day 21 of gestation, dams received a 2-h infusion of l-[1-(13)C]-valine until fetuses were extracted by cesarean delivery. Isotope enrichments were measured in free amino acids and fetal muscle, liver, and placenta protein by GC-mass spectrometry. RESULTS: Fetal weight was ~29% lower in the LP group (3.82 +/- 0.06 g) than in the control group (5.41 +/- 0.10 g) (P < 0.001). Regardless of supplementation, fetal weight remained below that of control fetuses. Yet, compared with the LP group, l-citrulline and l-arginine equally increased fetal weight to 4.15 +/- 0.08 g (P < 0.05) and 4.13 +/- 0.1 g (P < 0.05 compared with LP), respectively, whereas NEAA did not (4.05 +/- 0.05 g; P = 0.07). Fetal muscle protein fractional synthesis rate was 35% lower in the LP fetuses (41% +/- 11%/d) than in the control (61% +/- 13%/d) fetuses (P < 0.001) and was normalized by l citrulline (56% +/- 4%/d; P < 0.05 compared with LP, NS compared with control) and not by other supplements. Urinary nitrite and nitrate excretion was lower in the LP group (6.4 +/- 0.8 MUmol/d) than in the control group (17.9 +/- 1.1 MUmol/d; P < 0.001) and increased in response to l-citrulline or l-arginine (12.1 +/- 2.2 and 10.6 +/- 0.9 MUmol/d; P < 0.05), whereas they did not in the LP + NEAA group. CONCLUSION: l-Citrulline increases fetal growth in a model of IUGR, and the effect may be mediated by enhanced fetal muscle protein synthesis and/or increased NO production. PMID- 26865648 TI - Effect of Ultraviolet Light-Exposed Mushrooms on Vitamin D Status: Liquid Chromatography-Tandem Mass Spectrometry Reanalysis of Biobanked Sera from a Randomized Controlled Trial and a Systematic Review plus Meta-Analysis. AB - BACKGROUND: Randomized controlled trial (RCT) data on the response of serum total 25-hydroxyvitamin D [25(OH)D] in healthy participants consuming UV light-exposed edible mushrooms are limited and mixed. OBJECTIVE: The objective was to undertake a systematic review and meta-analysis of responses of serum 25(OH)D [and serum 25 hydroxyergocalciferol, 25(OH)D2, and serum 25-hydroxycholecalciferol, 25(OH)D3, if available] to consumption of UV-exposed mushrooms by healthy participants. Biobanked sera from one RCT (originally analyzed by immunoassay) were reanalyzed by LC-MS/MS to generate serum 25(OH)D2 and serum 25(OH)D3 data. METHODS: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched for RCTs of UV-exposed mushrooms and data on serum 25(OH)D. Studies were screened for eligibility, and relevant data were extracted. Serum 25(OH)D data were re-analyzed by ANOVA and paired t tests. RESULTS: Our structured search yielded 6 RCTs meeting our inclusion criteria. Meta-analysis of all 6 RCTs showed serum 25(OH)D was not significantly increased (P = 0.12) by UV-exposed mushrooms, but there was high heterogeneity (I(2) = 87%). Including only the 3 European-based RCTs [mean baseline 25(OH)D, 38.6 nmol/L], serum 25(OH)D was increased significantly by UV exposed mushrooms [weighted mean difference (WMD): 15.2 nmol/L; 95% CI: 1.5, 28.8 nmol/L, P = 0.03, I(2) = 88%], whereas there was no significant effect in the 3 US-based RCTs [P = 0.83; mean baseline 25(OH)D: 81.5 nmol/L]. Analysis of serum 25(OH)D2 and serum 25(OH)D3 (n = 5 RCTs) revealed a statistically significant increase (WMD: 20.6 nmol/L; 95% CI: 8.0, 33.3 nmol/L, P = 0.001, I(2 =) 99%) and decrease (WMD: -13.3 nmol/L; 95% CI: -15.8, -10.7 nmol/L, P < 0.00001, I(2) = 0%) after supplementation with UV-exposed mushrooms. CONCLUSIONS: Consumption of UV exposed mushrooms may increase serum 25(OH)D when baseline vitamin D status is low via an increase in 25(OH)D2 (24.2 nmol/L) and despite a concomitant but relatively smaller reduction in 25(OH)D3 (-12.6 nmol/L). When baseline vitamin D status is high, the mean increase in 25(OH)D2 (18.3 nmol/L) and a relatively similar reduction in 25(OH)D3 (-13.6 nmol/L) may explain the lack of effect on serum 25(OH)D. PMID- 26865649 TI - Protein Concentration in Milk Formula, Growth, and Later Risk of Obesity: A Systematic Review. AB - BACKGROUND: Protein intake may influence important health outcomes in later life. OBJECTIVE: The objective of this study was to investigate current evidence on the effects of infant formulas and follow-on formulas with different protein concentrations on infants' and children's growth, body composition, and later risk of overweight and obesity. METHODS: In this systematic review, we searched electronic databases (including MEDLINE, Embase, and the Cochrane Library) up until November 2014 for randomized controlled trials (RCTs). Eligible studies had to include children aged 0-3 y who represented the general population and were fed cow milk-based infant formulas with variations in protein concentration. Control groups received lower-protein cow milk-based formulas (as defined by the authors). The primary outcomes were growth, overweight, obesity, and adiposity. Various time points for outcomes assessment were accepted for inclusion. If possible, a meta-analysis was performed. RESULTS: Twelve RCTs met our inclusion criteria. Different formula protein concentrations did not affect linear growth other than a transient effect on mean length at 3 mo observed in a meta-analysis of 4 studies (mean difference, - 0.27 cm; 95% CI: -0.52, -0.02). Lower mean weight and weight z scores obtained from the infants fed lower-protein formulas were observed only from 6 to 12 mo of age. Data from one large RCT showed that consumption of a lower-protein infant formula may reduce body mass index at 12 mo of age and later (12 mo, 24 mo, and 6y) and the risk of obesity at 6 y. Effects on body composition remained unclear. CONCLUSIONS: The current evidence is insufficient for assessing the effects of reducing the protein concentration in infant formulas on long-term outcomes, but, if confirmed, this could be a promising intervention for reducing the risk of overweight and obesity in children. In view of the limited available evidence, more studies replicating effects on long-term health outcomes are needed. PMID- 26865646 TI - Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARgamma Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study. AB - BACKGROUND: Although the peroxisome proliferator-activated receptor gamma (PPARgamma) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARgamma pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein beta (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARgamma gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARgamma pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation. PMID- 26865650 TI - Breakfast-Skipping and Selecting Low-Nutritional-Quality Foods for Breakfast Are Common among Low-Income Urban Children, Regardless of Food Security Status. AB - BACKGROUND: Universal access to the School Breakfast Program (SBP) is intended to help low-income and food-insecure students overcome barriers to eating breakfast. However, SBP participation is often still low despite universal access. Further information is needed with regard to these children's breakfast behaviors, and in particular breakfast behaviors among youth from food-insecure families, to inform effective breakfast interventions. OBJECTIVES: The objective of this study was to examine breakfast behaviors among a large sample of urban students with universal access to the SBP and to identify differences in breakfast behaviors among children from food-secure compared with food-insecure households. METHODS: A cross-sectional study of 821 fourth- through sixth-grade students and their parents from 16 schools was conducted. Students reported the foods/drinks selected and location of obtaining food/drink on the morning of data collection, parents reported household food security status using the 6-item Food Security Survey Module, and the school district provided SBP participation data during the fall semester of 2013. Multivariable linear regression models accounting for school-level clustering were used to examine differences in breakfast behaviors across 3 levels of household food security: food secure, low food secure, and very low food secure. RESULTS: Students participated in the SBP 31.2% of possible days, with 13% never participating in the SBP. One-fifth (19.4%) of students purchased something from a corner store for breakfast, and 16.9% skipped breakfast. Forty-six percent of students were food insecure; few differences in breakfast behaviors were observed across levels of food security. CONCLUSIONS: Despite universal access to the SBP, participation in the SBP is low. Breakfast skipping and selection of foods of low nutritional quality in the morning are common, regardless of household food security status. Additional novel implementation of the SBP and addressing students' breakfast preferences may be necessary to further reduce barriers to students obtaining a free, healthful breakfast. This trial was registered at clinicaltrials.gov as NCT01924130. PMID- 26865651 TI - The Circulating Concentration and 24-h Urine Excretion of Magnesium Dose- and Time-Dependently Respond to Oral Magnesium Supplementation in a Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND: Accurate determination of Mg status is important for improving nutritional assessment and clinical risk stratification. OBJECTIVE: We aimed to quantify the overall responsiveness of Mg biomarkers to oral Mg supplementation among adults without severe diseases and their dose- and time responses using available data from randomized controlled trials (RCTs). METHODS: We identified 48 Mg supplementation trials (n = 2131) through searches of MEDLINE and the Cochrane Library up to November 2014. Random-effects meta-analysis was used to estimate weighted mean differences of biomarker concentrations between intervention and placebo groups. Restricted cubic splines were used to determine the dose- and time responses of Mg biomarkers to supplementation. RESULTS: Among the 35 biomarkers assessed, serum, plasma, and urine Mg were most commonly measured. Elemental Mg supplementation doses ranged from 197 to 994 mg/d. Trials ranged from 3 wk to 5 y (median: 12 wk). Mg supplementation significantly elevated circulating Mg by 0.04 mmol/L (95% CI: 0.02, 0.06) and 24-h urine Mg excretion by 1.52 mmol/24 h (95% CI: 1.20, 1.83) as compared to placebo. Circulating Mg concentrations and 24-h urine Mg excretion responded to Mg supplementation in a dose- and time-dependent manner, gradually reaching a steady state at doses of 300 mg/d and 400 mg/d, or after ~20 wk and 40 wk, respectively (all P-nonlinearity <= 0.001). The higher the circulating Mg concentration at baseline, the lower the responsiveness of circulating Mg to supplementation, and the higher the urinary excretion (all P-linearity < 0.05). In addition, RBC Mg, fecal Mg, and urine calcium were significantly more elevated by Mg supplementation than by placebo (all P-values < 0.05), but there is insufficient evidence to determine their responses to increasing Mg doses. CONCLUSIONS: This meta-analysis of RCTs demonstrated significant dose- and time responses of circulating Mg concentration and 24-h urine Mg excretion to oral Mg supplementation. PMID- 26865652 TI - Dietary Broccoli Lessens Development of Fatty Liver and Liver Cancer in Mice Given Diethylnitrosamine and Fed a Western or Control Diet. AB - BACKGROUND: The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli. OBJECTIVE: We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet-enhanced liver cancer. METHODS: Adult 5 wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old. RESULTS: Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68(+) macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides. CONCLUSION: Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice. PMID- 26865653 TI - Behavioral and Neural Markers of Flexible Attention over Working Memory in Aging. AB - Working memory (WM) declines as we age and, because of its fundamental role in higher order cognition, this can have highly deleterious effects in daily life. We investigated whether older individuals benefit from flexible orienting of attention within WM to mitigate cognitive decline. We measured magnetoencephalography (MEG) in older adults performing a WM precision task with cues during the maintenance period that retroactively predicted the location of the relevant items for performance (retro-cues). WM performance of older adults significantly benefitted from retro-cues. Whereas WM maintenance declined with age, retro-cues conferred strong attentional benefits. A model-based analysis revealed an increase in the probability of recalling the target, a lowered probability of retrieving incorrect items or guessing, and an improvement in memory precision. MEG recordings showed that retro-cues induced a transient lateralization of alpha (8-14 Hz) and beta (15-30 Hz) oscillatory power. Interestingly, shorter durations of alpha/beta lateralization following retro cues predicted larger cueing benefits, reinforcing recent ideas about the dynamic nature of access to WM representations. Our results suggest that older adults retain flexible control over WM, but individual differences in control correspond to differences in neural dynamics, possibly reflecting the degree of preservation of control in healthy aging. PMID- 26865655 TI - A Validated Stability Indicating RP-HPLC Method for the Determination of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir and Cobicistat in Pharmaceutical Dosage Form. AB - A new simple, rapid stability indicating assay method has been developed and validated for the determination of emtricitabine, tenofovir disoproxil fumarate, elvitegravir and cobicistat using reverse-phase high-performance liquid chromatography in their pharmaceutical dosage form. The chromatographic separation was performed on an ODS column (250 * 4.6 mm, 5 um) using mobile phase A (potassium dihydrogen orthophosphate, pH adjusted to 2.5) and mobile phase B (acetonitrile) in the ratio of 55:45% v/v at a flow rate of 1 mL/min. The analytes were detected at 250 nm. The method was found to be linear in the concentration range of 2-12 ug/mL for EMT, 3-18 ug/mL for TNDF, 1.5-9 ug/mL for ELV and COB, with the coefficient value (R(2)) of >0.9990. The accuracy was measured via recovery studies and found to be acceptable, and the percentage recoveries were found in the range of 99.93-100.08 +/- 0.5%. Forced degradation studies were also conducted, and the drugs were subjected to various stress conditions such as acid hydrolysis, base hydrolysis, oxidative, photolytic and thermal degradation. The proposed method was successfully validated and applied for the quantitative estimation of these drugs in both bulk and tablet dosage forms. PMID- 26865654 TI - Welding, a risk factor of lung cancer: the ICARE study. AB - OBJECTIVES: We investigated the relationship between lung cancer and occupational exposure to welding activity in ICARE, a population-based case-control study. METHODS: Analyses were restricted to men (2276 cases, 2780 controls). Welding exposure was assessed through detailed questionnaires, including lifelong occupational history. ORs were computed using unconditional logistic regression, adjusted for lifelong cigarette smoking and occupational exposure to asbestos. RESULTS: Among the regular welders, welding was associated with a risk of lung cancer (OR=1.7, 95% CI 1.1 to 2.5), which increased with the duration (OR=2.0, 95% CI 1.0 to 3.9 when duration >10 years), and was maximum 10-20 years since last welding. The risk was more pronounced in case of gas welding (OR=2.0, 95% CI 1.2 to 3.3), when the workpiece was covered by paint, grease, or other substances (OR=2.0, 95% CI 1.2 to 3.4) and when it was cleaned with chemical substances before welding. No statistically significant increase in lung cancer risk was observed among occasional welders. CONCLUSIONS: Although these results should be confirmed, we showed that type of welding and mode of workpiece preparation are important determinants of the lung cancer risk in regular welders. PMID- 26865656 TI - Determination of Five Major 8-Prenylflavones in Leaves of Epimedium by Solid Phase Extraction Coupled with Capillary Electrophoresis. AB - A simple, accurate and reproducible method which is based on the capillary electrophoresis, coupled with solid-phase extraction, has been developed for simultaneous determination of multiple 8-prenylflavones from Chinese Herba Epimedii. In this study, the author has mainly illustrated the experimental process and research results of five major components including epimedin C, icariin, diphylloside A, epimedoside A and icarisoside A that have been extracted and identified from Herba Epimedii for the first time. Experimental conditions have been optimized to achieve the best separation efficiency for the following factors: the buffer pH, buffer concentration and applied voltage. The experiment can be conducted through two separable stages: the first stage is to obtain the crude extracts through the solid-phase extraction; and the second stage is to further separate five major components by using the capillary electrophoresis. The separation of the five components and the analysis of the experiment are relatively fast and can be completed within 20 min. The concentration ranges of the construction of standard curves of five major 8-prenylflavones are 32.0 395.0, 23.4-292.0, 42.1-526.0, 18.8-233.5 and 29.7-371.0 ug mL(-1) respectively, which have showed acceptable linearity with a correlation coefficient, r >= 0.999. The coefficient varies within 2.0% for both intra- and inter-days tests. The recoveries of five components range from 92.3 to 104.1%. The relative standard deviations of recoveries of five components range from 1.2 and 2.8%. This new method will facilitate the extraction and expedite the determination of medical components from Herba Epimedii. PMID- 26865657 TI - Multimodal Assessment of Body Pain in Orofacial Pain Patients. AB - OBJECTIVE: . Patients with complaints of orofacial pain (OFP) often have other body pain, yet many do not report these to their providers. Uncontrolled pain at any location may impact the successful management of an OFP complaint. The objective of this study was to determine the number of pain regions throughout the body, and the underreporting of pain, in patients who presented to a tertiary military OFP clinic. DESIGN: A retrospective chart review was conducted on 423 consecutive new patients. Patients were given three assessment opportunities to report their pain on a whole-body pain map: 1) prior to evaluation (Pt1), 2) following an explanatory statement by their provider on the relationship between pain and prognosis (Pt2), and 3) during directed pain inquiry of specific body regions (Pro). The pain map was divided into nine anatomical regions that were assessed for the presence of pain after Pt1, Pt2, and Pro. RESULTS: Initially, 60.5% of patients did not report all pain locations (Pt1). Following the explanatory statement (Pt2), 30.5% still did not report all pain. Following the completion of all assessment methods, the most commonly reported number of pain regions was five (17.0%), and 91.5% of patients reported multiple pain regions. CONCLUSIONS: Most patients had multiple pain complaints outside the chief complaint, yet the majority did not report these until multiple forms of assessment were utilized. These data encourage the use of a pain map, a verbal pain explanation, and directed pain questioning to more accurately capture pain location and facilitate multidisciplinary care. PMID- 26865658 TI - Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies. AB - BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability. METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmo Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4*10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6*10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG*BMI interaction effect (Pinteraction=6.0*10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5*10(-7)). In the meta analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG*BMI*sex) was observed (Pinteraction=0.03), where the WGRSTG*BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci. CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females. PMID- 26865659 TI - In vivo quantification of gentamicin released from an implant coating. AB - Drug-releasing implants are gaining increasing interest. The present study reports a detailed physicochemical analysis of a polymeric coating based on poly(D,L-lactide) and the incorporated gentamicin combined with an in vitro and in vivo study of the gentamicin release. Differential scanning calorimeter, Fourier transform infrared spectroscopy, gel permeation chromatography and high performance liquid chromatography showed no effect of the gamma sterilisation on the coating components or an interaction of the polymer and the gentamicin. Microbiological analysis revealed an inhibition of bacterial growth on the implant surface. For the in vivo study, gentamicin-coated wires were implanted into the tibiae of rats and harvested at different time points up to day 42. To monitor the release in vivo, gentamicin was quantified in serum, bone, endosteum, kidney, and on the explanted wires. Gentamicin was detectable over a time period of 42 days in the endosteum, up to seven days in the kidney, up to 4 h in the bone and at the end of the experiment on one of eight wires. The locally released gentamicin caused no histological changes of the kidney. Microbiologically active concentrations of released gentamicin were found in the endosteum up to 4 h after implantation. The combination of different methods supports the individual results, where quantification is complemented by visualisation or antimicrobial activity. This work demonstrates that the coating procedure results in no substantial alteration of the incorporated drug and that the in vitro burst release occurs also in vivo. PMID- 26865660 TI - Performance and Limitations of Phosphate Quantification: Guidelines for Plant Biologists. AB - Phosphate (Pi) is a macronutrient that is essential for plant life. Several regulatory components involved in Pi homeostasis have been identified, revealing a very high complexity at the cellular and subcellular levels. Determining the Pi content in plants is crucial to understanding this regulation, and short real time(33)Pi uptake imaging experiments have shown Pi movement to be highly dynamic. Furthermore, gene modulation by Pi is finely controlled by localization of this ion at the tissue as well as the cellular and subcellular levels. Deciphering these regulations requires access to and quantification of the Pi pool in the various plant compartments. This review presents the different techniques available to measure, visualize and trace Pi in plants, with a discussion of the future prospects. PMID- 26865661 TI - Combining -Omics to Unravel the Impact of Copper Nutrition on Alfalfa (Medicago sativa) Stem Metabolism. AB - Copper can be found in the environment at concentrations ranging from a shortage up to the threshold of toxicity for plants, with optimal growth conditions situated in between. The plant stem plays a central role in transferring and distributing minerals, water and other solutes throughout the plant. In this study, alfalfa is exposed to different levels of copper availability, from deficiency to slight excess, and the impact on the metabolism of the stem is assessed by a non-targeted proteomics study and by the expression analysis of key genes controlling plant stem development. Under copper deficiency, the plant stem accumulates specific copper chaperones, the expression of genes involved in stem development is decreased and the concentrations of zinc and molybdenum are increased in comparison with the optimum copper level. At the optimal copper level, the expression of cell wall-related genes increases and proteins playing a role in cell wall deposition and in methionine metabolism accumulate, whereas copper excess imposes a reduction in the concentration of iron in the stem and a reduced abundance of ferritins. Secondary ion mass spectrometry (SIMS) analysis suggests a role for the apoplasm as a copper storage site in the case of copper toxicity. PMID- 26865662 TI - Transient increase of fractional anisotropy in reversible vasogenic edema. AB - Brain vasogenic edema, involving disruption of the blood-brain barrier, is a common pathological condition in several neurological diseases, with a heterogeneous prognosis. It is sometimes reversible, as in posterior reversible encephalopathy syndrome, but often irreversible and our current clinical tools are insufficient to reveal its reversibility. Here, we show that increased fractional anisotropy in magnetic resonance imaging is associated with the reversibility of vasogenic edema. Spontaneously, hypertensive rats-stroke prone demonstrated posterior reversible encephalopathy syndrome-like acute encephalopathy in response to high-dose cyclosporine A treatment; the deteriorating neurological symptoms and worsening scores in behavioral tests, which were seen in acute phase, dissappered after recovery by cessation of cyclosporine A. In the acute phase of encephalopathy, the fractional anisotropy and apparent diffusion coefficient increased in areas with IgG leakage. This increase of fractional anisotropy occurred in the absence of demyelination: fluid leakage into the myelinated space increased the axial, but not the radial, diffusivity, resulting in the increased fractional anisotropy. This increased fractional anisotropy returned to pre-encephalopathy values in the recovery phase. Our results highlight the importance of the fractional anisotropy increase as a marker for the reversibility of brain edema, which can delineate the brain areas for which recovery is possible. PMID- 26865664 TI - Colorimetric Evaluation of the Viability of the Microalga Dunaliella Salina as a Test Tool for Nanomaterial Toxicity. AB - A diagnostic test system was developed to determine the toxicity of nanomaterials to the saltwater microalga Dunaliella salina through evaluation of cell death and changes in the culture growth rate at various toxicant concentrations, providing LC50 and other toxicological metrics. The viability of cells was shown to decrease with decreasing chlorophyll absorption of red light by damaged cells. This correlation was confirmed by independent fluorescence microscopic measurements of live and dead cells in the population. Two standard colorless pollutants, hydrogen peroxide and formaldehyde, were used to validate the colorimetric method. The method's performance is exemplified with three Ag containing preparations (Ag nitrate, Ag proteinate, and 20-nm Ag nanoparticles) and with cetyltrimethylammonium bromide (CTAB) mixed with colloidal 15-nm Au and 20-nm Ag nanoparticles. The toxicity of the Ag-containing preparations to D. salina decreased in the order Ag nitrate >= Ag proteinate ? colloidal Ag. The toxicity of colloidal Au-CTAB mixtures was found to depend mostly on the content of free CTAB. The toxicity of colloidal Ag increased substantially in the presence of CTAB. The results suggest that our D. salina-based colorimetric test system can be used for simple and rapid preliminary screening of the toxicity of different nanomaterials. PMID- 26865663 TI - Tungsten Promotes Sex-Specific Adipogenesis in the Bone by Altering Differentiation of Bone Marrow-Resident Mesenchymal Stromal Cells. AB - Tungsten is a naturally occurring metal that increasingly is being incorporated into industrial goods and medical devices, and is recognized as an emerging contaminant. Tungsten preferentially and rapidly accumulates in murine bone in a concentration-dependent manner; however the effect of tungsten deposition on bone biology is unknown. Other metals alter bone homeostasis by targeting bone marrow derived mesenchymal stromal cell (MSC) differentiation, thus, we investigated the effects of tungsten on MSCsin vitroandin vivoIn vitro, tungsten shifted the balance of MSC differentiation by enhancing rosiglitazone-induced adipogenesis, which correlated with an increase in adipocyte content in the bone of tungsten exposed, young, male mice. Conversely, tungsten inhibited osteogenesis of MSCsin vitro; however, we found no evidence that tungsten inhibited osteogenesisin vivo Interestingly, two factors known to influence adipogenesis are sex and age of mice. Both female and older mice have enhanced adipogenesis. We extended our study and exposed young female and adult (9-month) male and female mice to tungsten for 4 weeks. Although tungsten accumulated to a similar extent in young female mice, it did not promote adipogenesis. Interestingly, tungsten did not accumulate in the bone of older mice; it was undetectable in adult male mice, and just above the limit of detect in adult female mice. Surprisingly, tungsten enhanced adipogenesis in adult female mice. In summary, we found that tungsten alters bone homeostasis by altering differentiation of MSCs, which could have significant implications for bone quality, but is highly dependent upon sex and age. PMID- 26865665 TI - NAD+ Supplementation Attenuates Methylmercury Dopaminergic and Mitochondrial Toxicity in Caenorhabditis Elegans. AB - Methylmercury (MeHg) is a neurotoxic contaminant of our fish supply that has been linked to dopaminergic (DAergic) dysfunction that characterizes Parkinson's disease. We have previously shown that MeHg causes both morphological and behavioral changes in the Caenorhabditis elegans DAergic neurons that are associated with oxidative stress. We were therefore interested in whether the redox sensitive cofactor nicotinamide adenine dinucleotide (NAD(+)) may be affected by MeHg and whether supplementation of NAD( + )may prevent MeHg-induced toxicities. Worms treated with MeHg showed depletion in cellular NAD( + )levels, which was prevented by NAD( + )supplementation prior to MeHg treatment. NAD( + )supplementation also prevented DAergic neurodegeneration and deficits in DAergic dependent behavior upon MeHg exposure. In a mutant worm line that cannot synthesize NAD( + )from nicotinamide, MeHg lethality and DAergic behavioral deficits were more sensitive to MeHg than wildtype worms, demonstrating the importance of NAD( + )in MeHg toxicity. In wildtype worms, NAD( + )supplementation provided protection from MeHg-induced oxidative stress and mitochondrial dysfunction. These data show the importance of NAD( + )levels in the response to MeHg exposure. NAD( + )supplementation may be beneficial for MeHg induced toxicities and preventing cellular damage involved in Parkinson's disease. PMID- 26865666 TI - Subacute Cardiovascular Toxicity of the Marine Phycotoxin Azaspiracid-1 in Rats. AB - Azaspiracids (AZAs) are marine toxins produced by Azadinium spinosum that get accumulated in filter feeding shellfish through the food-web. The first intoxication was described in The Netherlands in 1990, and since then several episodes have been reported worldwide. Azaspiracid-1, AZA-2, and AZA-3 presence in shellfish is regulated by food safety authorities of several countries to protect human health. Azaspiracids have been related to widespread organ damage, tumorogenic properties and acute heart rhythm alterations in vivo but the mechanism of action remains unknown. Azaspiracid toxicity kinetics in vivo and in vitro suggests accumulative effects. We studied subacute cardiotoxicity in vivo after repeated exposure to AZA-1 by evaluation of the ECG, arterial blood pressure, plasmatic heart damage biomarkers, and myocardium structure and ultrastructure. Our results showed that four administrations of AZA-1 along 15 days caused functional signs of heart failure and structural heart alterations in rats at doses ranging from 1 to 55 ug/kg. Azaspiracid-1 altered arterial blood pressure, tissue inhibitors of metalloproteinase-1 plasma levels, heart collagen deposition, and ultrastructure of the myocardium. Overall, these data indicate that repeated exposure to low amounts of AZA-1 causes cardiotoxicity, at doses that do not induce signs of other organic system toxicity. Remarkably, human exposure to AZAs considering current regulatory limits of these toxins may be dangerously close to clearly cardiotoxic doses in rats. These findings should be considered when human risk is estimated particularly in high cardiovascular risk subpopulations. PMID- 26865667 TI - Dose- and Time-Dependent Transcriptional Response of Ishikawa Cells Exposed to Genistein. AB - To further define the utility of the Ishikawa cells as a reliable in vitro model to determine the potential estrogenic activity of chemicals of interest, transcriptional changes induced by genistein (GES) in Ishikawa cells at various doses (10 pM, 1 nM, 100 nM, and 10 MUM) and time points (8, 24, and 48 h) were identified using a comprehensive microarray approach. Trend analysis indicated that the expression of 5342 unique genes was modified by GES in a dose- and time dependent manner (P <= 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest dose of GES evaluated (10 MUM). The GES' estrogenic activity was identified by comparing the Ishikawa cells' response to GES versus 17 alpha-ethynyl estradiol (EE, at equipotent doses, ie, 10 MUM vs 1 MUM, respectively) and was defined by changes in the expression of 284 unique genes elicited by GES and EE in the same direction, although the magnitude of the change for some genes was different. Further, comparing the response of the Ishikawa cells exposed to high doses of GES and EE versus the response of the juvenile rat uterus exposed to EE, we identified 66 unique genes which were up- or down regulated in a similar manner in vivo as well as in vitro Genistein elicits changes in multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response and offer an in vitro model to assess this mode of action. PMID- 26865668 TI - Estimating Margin of Exposure to Thyroid Peroxidase Inhibitors Using High Throughput in vitro Data, High-Throughput Exposure Modeling, and Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling. AB - Some pharmaceuticals and environmental chemicals bind the thyroid peroxidase (TPO) enzyme and disrupt thyroid hormone production. The potential for TPO inhibition is a function of both the binding affinity and concentration of the chemical within the thyroid gland. The former can be determined through in vitro assays, and the latter is influenced by pharmacokinetic properties, along with environmental exposure levels. In this study, a physiologically based pharmacokinetic (PBPK) model was integrated with a pharmacodynamic (PD) model to establish internal doses capable of inhibiting TPO in relation to external exposure levels predicted through exposure modeling. The PBPK/PD model was evaluated using published serum or thyroid gland chemical concentrations or circulating thyroxine (T4) and triiodothyronine (T3) hormone levels measured in rats and humans. After evaluation, the model was used to estimate human equivalent intake doses resulting in reduction of T4 and T3 levels by 10% (ED10) for 6 chemicals of varying TPO-inhibiting potencies. These chemicals were methimazole, 6-propylthiouracil, resorcinol, benzophenone-2, 2 mercaptobenzothiazole, and triclosan. Margin of exposure values were estimated for these chemicals using the ED10 and predicted population exposure levels for females of child-bearing age. The modeling approach presented here revealed that examining hazard or exposure alone when prioritizing chemicals for risk assessment may be insufficient, and that consideration of pharmacokinetic properties is warranted. This approach also provides a mechanism for integrating in vitro data, pharmacokinetic properties, and exposure levels predicted through high-throughput means when interpreting adverse outcome pathways based on biological responses. PMID- 26865669 TI - Moving Toward Integrating Gene Expression Profiling Into High-Throughput Testing: A Gene Expression Biomarker Accurately Predicts Estrogen Receptor alpha Modulation in a Microarray Compendium. AB - Microarray profiling of chemical-induced effects is being increasingly used in medium- and high-throughput formats. Computational methods are described here to identify molecular targets from whole-genome microarray data using as an example the estrogen receptor alpha (ERalpha), often modulated by potential endocrine disrupting chemicals. ERalpha biomarker genes were identified by their consistent expression after exposure to 7 structurally diverse ERalpha agonists and 3 ERalpha antagonists in ERalpha-positive MCF-7 cells. Most of the biomarker genes were shown to be directly regulated by ERalpha as determined by ESR1 gene knockdown using siRNA as well as through chromatin immunoprecipitation coupled with DNA sequencing analysis of ERalpha-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm by comparison to annotated gene expression datasets from experiments using MCF-7 cells, including those evaluating the transcriptional effects of hormones and chemicals. Using 141 comparisons from chemical- and hormone-treated cells, the biomarker gave a balanced accuracy for prediction of ERalpha activation or suppression of 94% and 93%, respectively. The biomarker was able to correctly classify 18 out of 21 (86%) ER reference chemicals including "very weak" agonists. Importantly, the biomarker predictions accurately replicated predictions based on 18 in vitro high-throughput screening assays that queried different steps in ERalpha signaling. For 114 chemicals, the balanced accuracies were 95% and 98% for activation or suppression, respectively. These results demonstrate that the ERalpha gene expression biomarker can accurately identify ERalpha modulators in large collections of microarray data derived from MCF-7 cells. PMID- 26865670 TI - MCPIP1 Regulates Alveolar Macrophage Apoptosis and Pulmonary Fibroblast Activation After in vitro Exposure to Silica. AB - BACKGROUND: Silicosis is a fatal and fibrotic pulmonary disease caused by the inhalation of silica. After arriving at the alveoli, silica is ingested by alveolar macrophages (AMOs), in which monocyte chemotactic protein-induced protein 1 (MCPIP1) plays an essential role in controlling macrophage-mediated inflammatory responses. However, the mechanism of action of MCPIP1 in silicosis is poorly understood. METHODS: Primary rat AMOs were isolated and treated with SiO2 (50 ug/cm(2)). MCPIP1 and AMO activation/apoptosis markers were detected by immunoblotting. MCPIP1 was down-regulated using siRNA in AMOs. The effects of AMOs on fibroblast activation and migration were evaluated using a gel contraction assay, a scratch assay, and a nested collagen matrix migration model. RESULTS: After exposure to SiO2, MCPIP1 was significantly increased in rat AMOs. Activation and apoptosis markers in AMOs were up-regulated after exposure to SiO2 Following siRNA-mediated silencing of MCPIP1 mRNA, the markers of AMO activation and apoptosis were significantly decreased. Rat pulmonary fibroblasts (PFBs) cultured in conditional medium from AMOs treated with MCPIP1 siRNA and SiO2 showed significantly less activation and migration compared with those cultured in conditional medium from AMOs treated with control siRNA and SiO2 CONCLUSION: Our data suggest a vital role for MCPIP1 in AMO apoptosis and PFB activation/migration induced by SiO2. PMID- 26865678 TI - The Application of Noninvasive Headspace Analysis to Media Fill Inspection. AB - The results of a proof-of-principle study demonstrating a new analytical technique for detecting microbial growth directly in pharmaceutical containers are described. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to nondestructively determine gas concentrations in the headspace of a media-filled pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. Once aerobic microorganisms begin to divide after the lag phase and enter the exponential growth phase, there will be significant consumption of oxygen and concomitant production of carbon dioxide in the sealed container. Laser-based headspace analysis can accurately measure these changes in the headspace gas composition. The carbon dioxide and oxygen measurement data for the representative microorganisms Staphylococcus aureus, Bacillus subtilis, Candida albicans, and Aspergillus brasiliensis were modeled using the Baranyi-Roberts equation. The mathematical modeling allowed quantitative comparisons to be made between the data from the different microorganisms as well as to the known growth curves based on microbial count. Because laser-based headspace analysis is noninvasive and can be automated to analyze the headspace of pharmaceutical containers at inspection speeds of several hundred containers per minute on-line, some potential new applications are enabled. These include replacing the current manual human visual inspection with an automated analytical inspection machine to determine microbial contamination of media fill and pharmaceutical drug product vials. LAY ABSTRACT: A novel analytical technique has been demonstrated for detecting microbial growth in media-filled pharmaceutical containers. This analytical technique, laser-based headspace analysis, uses tunable diode laser absorption spectroscopy to determine gas concentrations in the headspace of a pharmaceutical container. For detecting microbial growth, the levels of headspace oxygen and carbon dioxide are measured. The study shows that once aerobic microorganisms begin to grow after the lag phase and enter the exponential growth phase there will be a significant consumption of oxygen in the sealed container as well as a corresponding production of carbon dioxide. Headspace analysis can accurately measure and monitor these changes in the headspace gas composition and could therefore be used to detect contaminated pharmaceutical containers. Because the technique can be automated to analyze hundreds of containers a minute on line, there are opportunities for implementing a headspace inspection machine to perform automated inspection of media fills used to validate aseptic filling operations. PMID- 26865679 TI - New Processes for Freeze-Drying in Dual-Chamber Systems. AB - Dual-chamber systems can offer self-administration and home care use for lyophilized biologics. Only a few products have been launched in dual-chamber systems so far-presumably due to dual-chamber systems' complex and costly drug product manufacturing process. Within this paper, two improved processes (both based on tray filling technology) for freeze-drying pharmaceuticals in dual chamber systems are described. Challenges with regards to heat transfer were tackled by (1) performing the freeze-drying step in a needle-down orientation in combination with an aluminum block, or (2) freeze-drying the drug product "externally" in a metal cartridge with subsequent filling of the lyophilized cake into the dual-chamber system. Metal-mediated heat transfer was shown to be efficient in both cases and batch (unit-to-unit) homogeneity with regards to sublimation rate was increased. It was difficult to influence ice crystal size using different methods when in use with an aluminum block due to its heat capacity. Using such a metal carrier implies a large heat capacity leading to relatively small ice crystals. Compared to the established process, drying times were reduced by half using the new processes. The drying time was, however, longer for syringes compared to vials due to the syringe design (long and slim). The differences in drying times were less pronounced for aggressive drying cycles. The proposed processes may help to considerably decrease investment costs into dual-chamber system fill-finish equipment. LAY ABSTRACT: Dual-chamber syringes offer self-administration and home care use for freeze-dried pharmaceuticals. Only a few products have been launched in dual-chamber syringes so far-presumably due to their complex and costly drug product manufacturing process. In this paper two improved processes for freeze-drying pharmaceuticals in dual-chamber syringes are described. The major challenge of freeze-drying is to transfer heat through a vacuum. The proposed processes cope with this challenge by (1) freeze-drying the drug product in the syringe in an orientation in which the product is closest to the heat source, or (2) freeze-drying the drug product outside the syringe in a metal tube. The latter requires filling the freeze-dried product subsequently into the dual-chamber syringe. Both processes were very efficient and promised to achieve similar freeze-drying conditions for all dual-chamber syringes within one production run. The proposed processes may help to considerably decrease investment costs into dual-chamber syringe fill finish equipment. PMID- 26865671 TI - In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood. AB - Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD, 1 MUg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 beta-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone induced urinary tract dysfunction later in life. PMID- 26865680 TI - Roflumilast Increases Bacterial Load and Dissemination in a Model of Pseudomononas Aeruginosa Airway Infection. AB - Exacerbations present a major clinical problem in many patients suffering from chronic obstructive pulmonary disease (COPD). Roflumilast, an inhibitor of phosphodiesterase 4, has shown beneficial effects in several clinical trials and is currently widely used to prevent exacerbations in severe COPD. Roflumilast has anti-inflammatory properties that may interfere with potentially important host defense functions, including cytotoxic properties of neutrophils at sites of inflammation. Since chronic bacterial infection is prevalent in severe COPD, Pseudomonas aeruginosa being a major pathogen, we hypothesized that this drug could impair host defense against P. aeruginosa. In this study, mice were pretreated with vehicle alone or roflumilast at doses of 5 mg/kg or 10 mg/kg, followed by instillation of P. aeruginosa in the airways. Bacterial load and dissemination, as well as inflammatory markers and immune cells, present in the airways were monitored. Roflumilast increased mortality, bacterial load, and dissemination in mice infected with P. aeruginosa. In addition, roflumilast treated mice had significantly lower numbers of neutrophils in the bronchi, but not in the lung tissue airways, compared with untreated mice. Several proinflammatory cytokines decreased in roflumilast-treated mice but in neither the neutrophil-recruiting chemokine KC nor IL-6. These findings show that roflumilast treatment impairs host defense against P. aeruginosa in the airways, which may indicate that patients suffering from chronic bacterial infection of the airways could benefit from withholding of treatment with roflumilast. PMID- 26865681 TI - Evaluation of Luminex xTAG Gastrointestinal Pathogen Panel Assay for Detection of Multiple Diarrheal Pathogens in Fecal Samples in Vietnam. AB - Diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. The diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. Multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. We evaluated the Luminex xTAG gastrointestinal pathogen panel (GPP) assay for the detection of common enteric bacterial and viral pathogens in Vietnam. Microbiological culture and real-time PCR were used as gold standards. The tests were performed on 479 stool samples collected from people admitted to the hospital for diarrheal disease throughout Vietnam. Sensitivity and specificity were calculated for the xTAG GPP for the seven principal diarrheal etiologies. The sensitivity and specificity for the xTAG GPP were >88% for Shigellaspp.,Campylobacterspp., rotavirus, norovirus genotype 1/2 (GI/GII), and adenovirus compared to those of microbiological culture and/or real-time PCR. However, the specificity was low (~60%) for Salmonella species. Additionally, a number of important pathogens that are not identified in routine hospital procedures in this setting, such as Cryptosporidiumspp. and Clostridium difficile, were detected with the GPP. The use of the Luminex xTAG GPP for the detection of enteric pathogens in settings, like Vietnam, would dramatically improve the diagnostic accuracy and capacity of hospital laboratories, allowing for timely and appropriate therapy decisions and a wider understanding of the epidemiology of pathogens associated with severe diarrheal disease in low-resource settings. PMID- 26865682 TI - Performance of the New Aptima HCV Quant Dx Assay in Comparison to the Cobas TaqMan HCV2 Test for Use with the High Pure System in Detection and Quantification of Hepatitis C Virus RNA in Plasma or Serum. AB - Quantitating the level of hepatitis C virus (HCV) RNA is the standard of care for monitoring HCV-infected patients during treatment. The performances of commercially available assays differ for precision, limit of detection, and limit of quantitation (LOQ). Here, we compare the performance of the Hologic Aptima HCV Quant Dx assay (Aptima) to that of the Roche Cobas TaqMan HCV test, version 2.0, using the High Pure system (HPS/CTM), considered a reference assay since it has been used in trials defining clinical decision points in patient care. The assays' performance characteristics were assessed using HCV RNA reference panels and plasma/serum from chronically HCV-infected patients. The agreement between the assays for the 3 reference panels was good, with a difference in quantitation values of <0.5 log. High concordance was demonstrated between the assays for 245 clinical samples (kappa = 0.80; 95% confidence interval [CI], 0.720 to 0.881); however, Aptima detected and/or quantitated 20 samples that HPS/CTM did not detect, while Aptima did not detect 1 sample that was quantitated by HPS/CTM. For the 165 samples quantitated by both assays, the values were highly correlated (R= 0.98;P< 0.0001). The linearity of quantitation from concentrations of 1.4 to 6 log was excellent for both assays for all HCV genotypes (GT) tested (GT 1a, 1b, 2b, and 3a) (R(2)> 0.99). The assays had similar levels of total and intra-assay variability across all genotypes at concentrations from 1,000 to 25 IU/ml. Aptima had a greater analytical sensitivity, quantitating more than 50% of replicates at 25-IU/ml target. Aptima showed performance characteristics comparable to those of HPS/CTM and increased sensitivity, making it suitable for use as a clinical diagnostic tool on the fully automated Panther platform. PMID- 26865684 TI - Inactivating Zaire Ebolavirus in Whole-Blood Thin Smears Used for Malaria Diagnosis. AB - Malaria is an important mimic or coinfection in potential Ebolavirus disease patients. Here, we evaluated the efficacy of the 100% methanol-inactivating Zaire Ebolavirus Makona variant for malaria thin-smear preparation. We determined that 100% methanol completely inactivated the virus after 15 min. PMID- 26865683 TI - Multiplex Antibody Detection for Noninvasive Genus-Level Diagnosis of Prosthetic Joint Infection. AB - We developed and evaluated a multiplex antibody detection-based immunoassay for the diagnosis of prosthetic joint infections (PJIs). Sixteen protein antigens from three Staphylococcusspecies (Staphylococcus aureus,Staphylococcus epidermidis, and Staphylococcus lugdunensis) (8 antigens),Streptococcus agalactiae(4 antigens), and Propionibacterium acnes(4 antigens) were selected by comparative immune proteomics using serum samples from PJI cases versus controls. A bead-based multiplex immunoassay that measured serum IgG against purified, recombinant forms of each of the 16 antigens was developed. We conducted a prospective study to evaluate the performance of the assay. A PJI was defined by the presence of a sinus tract and/or positive intraoperative sample cultures (at least one sample yielding a virulent organism or at least two samples yielding the same organism). A total of 455 consecutive patients undergoing revision or resection arthroplasty (hip, 66.3%; knee, 29.7%; shoulder, 4%) at two French reference centers for the management of PJI were included: 176 patients (38.7%) were infected and 279 (61.3%) were not. About 60% of the infections involved at least one of the species targeted by the assay. The sensitivity/specificity values were 72.3%/80.7% for targeted staphylococci, 75%/92.6% forS. agalactiae, and 38.5%/84.8% forP. acnes The assay was more sensitive for infections occurring >3 months after arthroplasty and for patients with an elevated C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR). However, it detected 64.3% and 58.3% of targeted staphylococcal infections associated with normal CRP and ESR values, respectively. This new multiplex immunoassay approach is a novel noninvasive tool to evaluate patients suspected of having PJIs and provides information complementary to that from inflammatory marker values. PMID- 26865685 TI - Analytical and Clinical Evaluation of the Epistem Genedrive Assay for Detection of Mycobacterium tuberculosis. AB - The Epistem Genedrive assay rapidly detects the Mycobacterium tuberculosis omplex from sputum and is currently available for clinical use. However, the analytical and clinical performance of this test has not been fully evaluated. The analytical limit of detection (LOD) of the Genedrive PCR amplification was tested with genomic DNA; the performance of the complete (sample processing plus amplification) system was tested by spiking M. tuberculosismc(2)6030 cells into distilled water andM. tuberculosis-negative sputum. Specificity was tested using common respiratory pathogens and nontuberculosis mycobacteria. A clinical evaluation enrolled adults with suspected pulmonary tuberculosis, obtained three sputum samples from each participant, and compared the accuracy of the Gene drive to that of the Xpert MTB/RIF assay using M. tuberculosiscultures as the reference standard. The Genedrive assay had an LOD of 1 pg/MUl (100 genomic DNA copies/reaction). The LODs of the system were 2.5 * 10(4)CFU/ml and 2.5 * 10(5)CFU/ml for cells spiked into water and sputum, respectively. False positiverpoBprobe signals were observed in 3/32 (9.4%) of the negative controls and also in few samples containing Mycobacterium abscessus,Mycobacterium gordonae, o rMycobacterium thermoresistibile In the clinical study, among 336 analyzed participants, the overall sensitivities for the tuberculosis case detection of Gene drive, Xpert, and smear microscopy were 45.4% (95% confidence interval [CI], 35.2% to 55.8%), 91.8% (95% CI, 84.4% to 96.4%), and 77.3% (95% CI, 67.7% to 85.2%), respectively. The sensitivities of Gene drive and Xpert for the detection of smear-microscopy-negative tuberculosis were 0% (95% CI, 0% to 15.4%) and 68.2% (95% CI, 45.1% to 86.1%), respectively. The Genedrive assay did not meet performance standards recommended by the World Health Organization for a smear microscopy replacement tuberculosis test. Epistem is working on modifications to improve the assay. PMID- 26865686 TI - Comparative Detection and Quantification of Arcobacter butzleri in Stools from Diarrheic and Nondiarrheic People in Southwestern Alberta, Canada. AB - Arcobacter butzleri has been linked to enteric disease in humans, but its pathogenicity and epidemiology remain poorly understood. The lack of suitable detection methods is a major limitation. Using comparative genome analysis, we developed PCR primers for direct detection and quantification ofA. butzleri DNA in microbiologically complex matrices. These primers, along with existing molecular and culture-based methods, were used to detectA. butzleri and enteric pathogens in stools of diarrheic and nondiarrheic people (n= 1,596) living in southwestern Alberta, Canada, from May to November 2008. In addition, quantitative PCR was used to compare A. butzleridensities in diarrheic and nondiarrheic stools.Arcobacter butzleriwas detected more often by PCR (59.6%) than by isolation methods (0.8%). Comparison by PCR-based detection found no difference in the prevalence ofA. butzleri between diarrheic (56.7%) and nondiarrheic (45.5%) individuals. Rates of detection in diarrheic stools peaked in June (71.1%) and October (68.7%), but there was no statistically significant correlation between the presence ofA. butzleri and patient age, sex, or place of habitation. Densities ofA. butzleriDNA in diarrheic stools (1.6 +/- 0.59 log10 copies mg(-1)) were higher (P= 0.007) than in nondiarrheic stools (1.3 +/- 0.63 log10copies mg(-1)). Of the 892 diarrheic samples that were positive for A. butzleri, 74.1% were not positive for other bacterial and/or viral pathogens. The current study supports previous work suggesting that A. butzleri pathogenicity is strain specific and/or dependent on other factors, such as the level of host resistance. PMID- 26865687 TI - Emergence of a Multidrug-Resistant Shiga Toxin-Producing Enterotoxigenic Escherichia coli Lineage in Diseased Swine in Japan. AB - EnterotoxigenicEscherichia coli(ETEC) and Shiga toxin-producingE. coli(STEC) are important causes of diarrhea and edema disease in swine. The majority of swine pathogenicE. colistrains belong to a limited range of O serogroups, including O8, O138, O139, O141, O147, O149, and O157, which are the most frequently reported strains worldwide. However, the circumstances of ETEC and STEC infections in Japan remain unknown; there have been few reports on the prevalence or characterization of swine-pathogenicE. coli In the present study, we determined the O serogroups of 967E. coliisolates collected between 1991 and 2014 from diseased swine in Japan, and we found that O139, O149, O116, and OSB9 (O serogroup ofShigella boydiitype 9) were the predominant serogroups. We further analyzed these four O serogroups using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing, and virulence factor profiling. Most of the O139 and O149 strains formed serogroup-specific PFGE clusters (clusters I and II, respectively), whereas the O116 and OSB9 strains were grouped together in the same cluster (cluster III). All of the cluster III strains belonged to a single sequence type (ST88) and carried genes encoding both enterotoxin and Shiga toxin. This PFGE cluster III/ST88 lineage exhibited a high level of multidrug resistance (to a median of 10 antimicrobials). Notably, these bacteria were resistant to fluoroquinolones. Thus, this lineage should be considered a significant risk to animal production due to the toxigenicity and antimicrobial resistance of these bacteria. PMID- 26865688 TI - Evaluation of GenoFlow DR-MTB Array Test for Detection of Rifampin and Isoniazid Resistance in Mycobacterium tuberculosis. AB - The aim of this study was to evaluate the GenoFlow DR-MTB array test (DiagCor Bioscience, Hong Kong) on 70 cultured isolates and 50 sputum specimens. The GenoFlow array test showed good sensitivity and specificity compared to the phenotypic Bactec 460TB. This array accurately detected mutations inrpoB,katG, andinhAassociated with resistance to rifampin and isoniazid. PMID- 26865689 TI - Mycobacterium and Aerobic Actinomycete Culture: Are Two Medium Types and Extended Incubation Times Necessary? AB - Mycobacterial cultures are historically performed using a liquid medium and a solid agar medium with an incubation period of up to 60 days. We performed a retrospective analysis of 21,494 mycobacterial and aerobic actinomycetes cultures performed over 10 months to determine whether two medium types remain necessary and to investigate whether culture incubation length can be shortened. Specimens were cultured using Bactec MGIT liquid medium and Middlebrook 7H11/S7H11 solid medium with incubation periods of 42 and 60 days, respectively. Time-to positivity and the identity of isolates recovered from each medium were evaluated. A total of 1,205/21,494 cultures (6%) were positive on at least one medium. Of the 1,353 isolates recovered, 1,110 (82%) were nontuberculous mycobacteria, 145 (11%) were aerobic actinomycetes, and 98 (7%) wereMycobacterium tuberculosiscomplex. Assessing medium types, 1,121 isolates were recovered from solid medium cultures, 922 isolates were recovered from liquid medium cultures, and 690 isolates were recovered on both media. Liquid cultures were positive an average of 10 days before solid cultures when the two medium types were positive (P< 0.0001). Isolates detected on solid medium after 6 weeks of incubation included 65 (5%) nontuberculous mycobacteria, 4 (0.3%) aerobic actinomycetes, and 2 (0.2%) isolates from theM. tuberculosiscomplex. Medical chart review suggested that most of these later-growing isolates were insignificant, as the diagnosis was already known, or they were considered colonizers/contaminants. This study reaffirms the need for both liquid medium and solid medium for mycobacterial and aerobic actinomycetes culture and demonstrates that solid medium incubation times may be reduced to 6 weeks without significantly impacting sensitivity. PMID- 26865690 TI - The Past, Present, and (Possible) Future of Serologic Testing for Lyme Disease. AB - Lyme disease prevails as the most commonly transmitted tick-borne infection in the United States, and serologic evaluation for antibodies to Borrelia burgdorferi remains the recommended modality for diagnosis. This review presents a brief historical perspective on the evolution of serologic assays for Lyme disease and provides a summary of the performance characteristics for the currently recommended two-tiered testing algorithm (TTTA). Additionally, a recently proposed alternative to the traditional TTTA is discussed, and novel methodologies, including immuno-PCR and metabolic profiling for Lyme disease, are outlined. PMID- 26865691 TI - Comparative Evaluation of the Novel bioNexia Legionella Test with the BinaxNOW Legionella Card Assay and the Sofia Legionella FIA Assay for Detection of Legionella pneumophila (Serogroup 1) Antigen in Urine Samples. AB - A new immunochromatographic test (bioNexiaLegionella; bioMerieux) for the detection ofLegionella pneumophilaurinary antigen was evaluated in 255 urine samples. The results were compared with those obtained by the BinaxNOW and SofiaLegionellatests. The novel test compared well with those currently in use. PMID- 26865692 TI - Development of a Highly Specific IgM Enzyme-Linked Immunosorbent Assay for Bartonella henselae Using Refined N-Lauroyl-Sarcosine-Insoluble Proteins for Serodiagnosis of Cat Scratch Disease. AB - The conventional anti-Bartonella henselaeIgM enzyme-linked immunosorbent assay (IgM-ELISA) methods for diagnosing cat scratch disease (CSD) remain poor in both sensitivity and specificity. We sought to develop an IgM-ELISA with improved accuracy in the serodiagnosis of CSD by exploring the antigens that are most suitable for an ELISA. We prepared 5 different protein antigens: antigen I (sonicatedB. henselaewhole-cell antigen), antigen II (N-lauroyl-sarcosine insoluble antigen), antigen III (processed sarcosine-soluble antigen), and antigen IV and antigen V (sarcosine-insoluble and sarcosine-soluble antigens refined by DEAE-Sepharose Fast Flow ion-exchange chromatography). The IgM antibodies in the sera of 47 patients with clinically suspected CSD (24 definite, 23 suspected) and of 85 healthy individuals were examined by ELISAs using the 5 antigens, and the results were compared with those of an IgM indirect fluorescent antibody assay (IgM-IFA). In a reference panel, which consisted of 5 positive and 5 negative sera, antigen I and antigen III failed to distinguish between the two statuses, whereas the other three antigens succeeded in distinguishing between them. When the cutoff value was set at the 98th percentile of the ELISA index for healthy individuals, the sensitivity of IgM-IFA for the 24 cases of definite CSD was 54%, whereas the sensitivities of the IgM-ELISAs with antigen II, IV, and V were 75%, 83%, and 75%, respectively. The sensitivities of these three IgM-ELISAs for all 47 of the clinically suspected cases were 49%, 64%, and 51%, respectively. In contrast, the sensitivity of IgM-IFA was 28%. These results indicate that the refined sarcosine-insoluble proteins (antigen IV), which possessed the highest specificity among the 5 antigens, are the most appropriate for developing an IgM-ELISA for the highly specific serodiagnosis of CSD. PMID- 26865694 TI - Identification of Low-Level Vancomycin Resistance in Staphylococcus aureus in the Era of Informatics. AB - Vancomycin-intermediateStaphylococcus aureus(VISA) and heteroresistant VISA (hVISA) are pathogens for which accurate antimicrobial susceptibility testing (AST) would rule out standard treatment with vancomycin. Unfortunately, AST for vancomycin is relatively slow and standard methods are unable to reliably detect VISA and hVISA. An article in this issue (C. A. Mather, B. J. Werth, S. Sivagnanam, D. J. SenGupta, and S. M. Butler-Wu, J Clin Microbiol 54:883-890, 2016, doi:http://dx.doi.org/10.1128/JCM.02428-15) describes a rapid whole-cell matrix-assisted laser desorption ionization-time of flight proxy susceptibility method that highlights current innovations and challenges with rapid AST, VISA/hVISA identification, and clinical bioinformatics. PMID- 26865693 TI - Antemortem Detection of Chronic Wasting Disease Prions in Nasal Brush Collections and Rectal Biopsy Specimens from White-Tailed Deer by Real-Time Quaking-Induced Conversion. AB - Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since spread to cervids in 23 states, two Canadian provinces, and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction of farmed or free-ranging deer and elk or surveillance studies of private or protected herds, where depopulation is contraindicated. This study sought to evaluate the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay by using recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brush samples collected antemortem from farmed white-tailed deer (n= 409). Antemortem findings were then compared to results from ante- and postmortem samples (RAMALT, brainstem, and medial retropharyngeal lymph nodes) evaluated by using the current gold standardin vitroassay, immunohistochemistry (IHC) analysis. We hypothesized that the sensitivity of RT-QuIC would be comparable to IHC analysis in antemortem tissues and would correlate with both the genotype and the stage of clinical disease. Our results showed that RAMALT testing by RT-QuIC assay had the highest sensitivity (69.8%) compared to that of postmortem testing, with a specificity of >93.9%. These data suggest that RT QuIC, like IHC analysis, is an effective assay for detection of PrP(CWD)in rectal biopsy specimens and other antemortem samples and, with further research to identify more sensitive tissues, bodily fluids, or experimental conditions, has potential for large-scale and rapid automated testing for CWD diagnosis. PMID- 26865695 TI - Are adolescent orphans more likely to be HIV-positive? A pooled data analyses across 19 countries in sub-Saharan Africa. AB - BACKGROUND: Despite extensive resources and numerous programmes directed towards orphans in sub-Saharan Africa, evidence of their disadvantage is surprisingly limited. While initial research suggests that orphans are at greater risk of being HIV-positive, the evidence is limited in geographic scope. METHODS: To rigorously test disparities in HIV prevalence related to orphanhood and parental HIV status in sub-Saharan Africa, we used Demographic and Health Survey data from 19 countries in sub-Saharan Africa. We conducted pooled multilevel logistic regression on adolescents aged 15-17 years with HIV test results (N=22 837 girls and 20 452 boys). RESULTS: Regardless of their gender, orphans who lost their mother, lost both parents or had an HIV-infected mother were two to three times more likely to test positive for HIV infection (ORs 1.87-3.17). The loss of a father was also associated with HIV infection risk for females, but of slightly lower magnitude (OR 1.63). CONCLUSIONS: To better inform interventions, future research is needed to quantify the relative contribution of perinatally-acquired and sexually-acquired infections, and to investigate the specific mechanisms that may account for disparities in the latter. In the meantime, programmes serving HIV-infect adults as well as those serving orphaned and vulnerable children should invest in family-based HIV testing in order to identify adolescents in need of treatment. PMID- 26865696 TI - A HAND2 Loss-of-Function Mutation Causes Familial Ventricular Septal Defect and Pulmonary Stenosis. AB - Congenital heart disease (CHD) is the most common developmental abnormality, and is the leading noninfectious cause of mortality in neonates. Increasing evidence demonstrates that genetic defects play an important role in the pathogenesis of CHD. However, CHD exhibits substantial heterogeneity, and the genetic determinants for CHD remain unknown in the overwhelming majority of cases. In the current study, the coding exons and flanking introns of the HAND2 gene, which encodes a basic helix-loop-helix transcription factor essential for normal cardiovascular development, were sequenced in 192 unrelated patients with CHD, and a novel heterozygous mutation, p.S65I, was identified in a patient with congenital ventricular septal defect (VSD). Genetic analysis of the index patient's pedigree revealed that the mutation was present in all seven affected family members available, but absent in the 13 unaffected family members examined. Besides, in addition to VSD, five of the proband's close relatives also had pulmonary stenosis (PS), and the proband's son also had double outlet right ventricle (DORV). The missense mutation, which altered an evolutionarily conserved amino acid, was absent in 300 unrelated, ethnically matched healthy individuals. Biological analyses using a dual-luciferase reporter assay system showed that the mutant HAND2 was associated with significantly diminished transcriptional activity. Furthermore, the mutation abolished the synergistic activation between HAND2 and GATA4, as well as NKX2.5-two other cardiac core transcriptional factors that have been causally linked to CHD. These findings indicate that HAND2 loss-of-function mutation contributes to human CHD, perhaps via its interaction with GATA4 and NKX2.5. PMID- 26865698 TI - Fluorescence In Situ Hybridization (FISH)-Based Karyotyping Reveals Rapid Evolution of Centromeric and Subtelomeric Repeats in Common Bean (Phaseolus vulgaris) and Relatives. AB - Fluorescence in situ hybridization (FISH)-based karyotyping is a powerful cytogenetics tool to study chromosome organization, behavior, and chromosome evolution. Here, we developed a FISH-based karyotyping system using a probe mixture comprised of centromeric and subtelomeric satellite repeats, 5S rDNA, and chromosome-specific BAC clones in common bean, which enables one to unambiguously distinguish all 11 chromosome pairs. Furthermore, we applied the karyotyping system to several wild relatives and landraces of common bean from two distinct gene pools, as well as other related Phaseolus species, to investigate repeat evolution in the genus Phaseolus Comparison of karyotype maps within common bean indicates that chromosomal distribution of the centromeric and subtelomeric satellite repeats is stable, whereas the copy number of the repeats was variable, indicating rapid amplification/reduction of the repeats in specific genomic regions. In Phaseolus species that diverged approximately 2-4 million yr ago, copy numbers of centromeric repeats were largely reduced or diverged, and chromosomal distributions have changed, suggesting rapid evolution of centromeric repeats. We also detected variation in the distribution pattern of subtelomeric repeats in Phaseolus species. The FISH-based karyotyping system revealed that satellite repeats are actively and rapidly evolving, forming genomic features unique to individual common bean accessions and Phaseolus species. PMID- 26865697 TI - High Throughput Analyses of Budding Yeast ARSs Reveal New DNA Elements Capable of Conferring Centromere-Independent Plasmid Propagation. AB - The ability of plasmids to propagate in Saccharomyces cerevisiae has been instrumental in defining eukaryotic chromosomal control elements. Stable propagation demands both plasmid replication, which requires a chromosomal replication origin (i.e., an ARS), and plasmid distribution to dividing cells, which requires either a chromosomal centromere for segregation or a plasmid partitioning element. While our knowledge of yeast ARSs and centromeres is relatively advanced, we know less about chromosomal regions that can function as plasmid partitioning elements. The Rap1 protein-binding site (RAP1) present in transcriptional silencers and telomeres of budding yeast is a known plasmid partitioning element that functions to anchor a plasmid to the inner nuclear membrane (INM), which in turn facilitates plasmid distribution to daughter cells. This Rap1-dependent INM-anchoring also has an important chromosomal role in higher-order chromosomal structures that enhance transcriptional silencing and telomere stability. Thus, plasmid partitioning can reflect fundamental features of chromosome structure and biology, yet a systematic screen for plasmid partitioning elements has not been reported. Here, we couple deep sequencing with competitive growth experiments of a plasmid library containing thousands of short ARS fragments to identify new plasmid partitioning elements. Competitive growth experiments were performed with libraries that differed only in terms of the presence or absence of a centromere. Comparisons of the behavior of ARS fragments in the two experiments allowed us to identify sequences that were likely to drive plasmid partitioning. In addition to the silencer RAP1 site, we identified 74 new putative plasmid-partitioning motifs predicted to act as binding sites for DNA binding proteins enriched for roles in negative regulation of gene expression and G2/M-phase associated biology. These data expand our knowledge of chromosomal elements that may function in plasmid partitioning and suggest underlying biological roles shared by such elements. PMID- 26865699 TI - A Genetic Map for the Only Self-Fertilizing Vertebrate. AB - The mangrove killifish Kryptolebias marmoratus, and its close relative Kryptolebias hermaphroditus, are the only vertebrate species known to reproduce by self-fertilization due to functional ovotestis development. To improve our understanding of their genomes, we constructed a genetic map. First, a single F1 fish was made by artificial fertilization between K. marmoratus and K. hermaphroditus strains. F2 progeny were then obtained by self-fertilization of the F1 fish. We used RAD-seq to query genomic DNAs from the two parental strains, the F1 individual and 49 F2 progeny. Results identified 9904 polymorphic RAD-tags (DNA markers) that mapped to 24 linkage groups, corresponding to the haploid chromosome number of these species. The total length of the map was 1248 cM, indicating that about one recombination occurred for each of the 24 homologous chromosome pairs in each meiosis. Markers were not evenly distributed along the chromosomes: in all chromosomes, many markers (> 8% of the total markers for each chromosome) mapped to chromosome tips. Centromeres suppress recombination, and this uneven distribution is probably due to the species' acrocentric chromosomes. Mapped marker sequences were compared to genomic sequences of medaka and platyfish, the next most closely related species with sequenced genomes that are anchored to genetic maps. Results showed that each mangrove killifish chromosome corresponds to a single chromosome of both platyfish and medaka, suggesting strong conservation of chromosomes over 100 million years of evolution. Our genetic map provides a framework for the K. marmoratus/K. hermaphroditus genome sequence and an important resource for understanding the biology of hermaphroditism. PMID- 26865700 TI - Efficient Software for Multi-marker, Region-Based Analysis of GWAS Data. AB - Genome-wide association studies (GWAS) have associated many single variants with complex disease, yet the better part of heritable complex disease risk remains unexplained. Analytical tools designed to work under specific population genetic models are needed. Rare variants are increasingly shown to be important in human complex disease, but most existing GWAS data do not cover rare variants. Explicit population genetic models predict that genes contributing to complex traits and experiencing recurrent, unconditionally deleterious, mutation will harbor multiple rare, causative mutations of subtle effect. It is difficult to identify genes harboring rare variants of large effect that contribute to complex disease risk via the single marker association tests typically used in GWAS. Gene/region based association tests may have the power detect associations by combining information from multiple markers, but have yielded limited success in practice. This is partially because many methods have not been widely applied. Here, we empirically demonstrate the utility of a procedure based on the rank truncated product (RTP) method, filtered to reduce the effects of linkage disequilibrium. We apply the procedure to the Wellcome Trust Case Control Consortium (WTCCC) data set, and uncover previously unidentified associations, some of which have been replicated in much larger studies. We show that, in the absence of significant rare variant coverage, RTP based methods still have the power to detect associated genes. We recommend that RTP-based methods be applied to all existing GWAS data to maximize the usefulness of those data. For this, we provide efficient software implementing our procedure. PMID- 26865702 TI - Mid-facial deformity secondary to a traumatic haemorrhage in a maxillary cyst. AB - Serious symptoms caused by intra-cystic bleeding are very rare. We describe a case of a maxillary cyst presenting with mid-facial deformity in a Japanese woman. She underwent bilateral Caldwell-Luc procedure 21 years earlier and suffered left cheek trauma 4 years earlier. She presented soon after the trauma complaining of left mid-facial deformity, and computed tomography showed a trilocular cystic lesion in the left maxilla. We performed facial osteotomy concurrent with cyst enucleation with lateral rhinotomy. Serosanguineous fluid filled the cyst cavity just below the face; however, additional cyst cavities contained straw-coloured fluid. She showed no signs of recurrence at the end of a 20-month follow-up, and her postoperative appearance was excellent. Histopathological examination showed that all cyst walls were lined by ciliated columnar epithelium, which was consistent with surgical ciliated cyst. We consider that the increased intra-cystic pressure caused by traumatic haemorrhage induced expansion of the pre-existing surgical ciliated cyst. PMID- 26865701 TI - The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ Cells from Heat Shock in Caenorhabditis elegans. AB - In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germline-the immortal cell lineage required for sexual reproduction-protection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the Caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation; protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures. PMID- 26865704 TI - Congenital prepubic sinus. PMID- 26865703 TI - 2016 Classification Criteria for Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation Collaborative Initiative. AB - To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (kappa=0.76). We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies. PMID- 26865705 TI - Excellent outcome of minimal residual disease-defined low-risk patients is sustained with more than 10 years follow-up: results of UK paediatric acute lymphoblastic leukaemia trials 1997-2003. AB - BACKGROUND: Minimal residual disease (MRD) is defined as the presence of sub microscopic levels of leukaemia. Measurement of MRD from bone marrow at the end of induction chemotherapy (day 28) for childhood acute lymphoblastic leukaemia (ALL) can highlight a large group of patients (>40%) with an excellent (>90%) short-term event-free survival (EFS). However, follow-up in recent published trials is relatively short, raising concerns about using this result to infer the safety of further therapy reduction in the future. METHODS: We examined MRD data on 225 patients treated on one of three UKALL trials between 1997 and 2003 to assess the long-term (>10 years follow-up) outcome of those patients who had low risk MRD (<0.01%) at day 28. RESULTS: Our pilot data define a cohort of 53% of children with MRD <0.01% at day 28 who have an EFS of 91% and long-term overall survival of 97%. Of 120 patients with day-28 MRD <0.01% and extended follow-up, there was one death due to treatment-related toxicity, one infectious death while in complete remission, and four relapse deaths. CONCLUSIONS: The excellent outcome for childhood ALL in patients with MRD <0.01% after induction chemotherapy is sustained for more than 10 years from diagnosis. This supports the potential exploration of further reduction of therapy in this group, in an attempt to reduce treatment-related mortality and late effects. PMID- 26865706 TI - Lymphatic Dissemination of Simian Immunodeficiency Virus after Penile Inoculation. AB - The human immunodeficiency virus (HIV) is primarily transmitted by heterosexual contact, and approximately equal numbers of men and women worldwide are infected with the virus. Understanding the biology of HIV acquisition and dissemination in men exposed to the virus by insertive penile intercourse is likely to help with the rational design of vaccines that can limit or prevent HIV transmission. To characterize the target cells and dissemination pathways involved in establishing systemic simian immunodeficiency virus (SIV) infection, we necropsied male rhesus macaques at 1, 3, 7, and 14 days after penile SIV inoculation and quantified the levels of unspliced SIV RNA and spliced SIV RNA in tissue lysates and the number of SIV RNA-positive cells in tissue sections. We found that penile (glans, foreskin, coronal sulcus) T cells and, to a lesser extent, macrophages and dendritic cells are primary targets of infection and that SIV rapidly reaches the regional lymph nodes. At 7 days after inoculation, SIV had disseminated to the blood, systemic lymph nodes, and mucosal lymphoid tissues. Further, at 7 days postinoculation (p.i.), spliced SIV RNA levels were the highest in the genital lymph nodes, indicating that this is the site where the infection is initially amplified. By 14 days p.i., spliced SIV RNA levels were high in all tissues, but they were the highest in the gastrointestinal tract, indicating that the primary site of virus replication had shifted from the genital lymph nodes to the gut. The stepwise pattern of virus replication and dissemination described here suggests that vaccine-elicited immune responses in the genital lymph nodes could help prevent infection after penile SIV challenge. IMPORTANCE: To be the most effective, vaccines should produce antiviral immune responses in the anatomic sites of virus replication. Thus, understanding the path taken by HIV from the mucosal surfaces, which are the site of virus exposure, to the deeper tissues where the virus replicates will provide insight into where AIDS vaccines should produce immunity to be the most effective. In this study, we determined that, by day 7 after penile inoculation, SIV has moved first to the inguinal lymph nodes and replicates to high levels. Although the virus is widely disseminated to other tissues by day 7, replication is largely limited to the inguinal lymph nodes. The step-by-step movement of SIV from penile mucosal surfaces to the draining lymph nodes may allow an HIV vaccine that produces immunity in these lymph nodes to block HIV from establishing an infection in an exposed person. PMID- 26865708 TI - Distinct Entry Mechanisms for Nonenveloped and Quasi-Enveloped Hepatitis E Viruses. AB - The hepatitis E virus (HEV) sheds into feces as nonenveloped virions but circulates in the blood in a membrane-associated, quasi-enveloped form (eHEV). Since the eHEV virions lack viral proteins on the surface, we investigated the entry mechanism for eHEV. We found that compared to nonenveloped HEV virions, eHEV attachment to the cell was much less efficient, requiring a longer inoculation time to reach its maximal infectivity. A survey of cellular internalization pathways identified clathrin-mediated endocytosis as the main route for eHEV entry. Unlike nonenveloped HEV virions, eHEV entry requires Rab5 and Rab7, small GTPases involved in endosomal trafficking, and blocking endosomal acidification abrogated eHEV infectivity. However, low pH alone was not sufficient for eHEV uncoating, suggesting that additional steps are required for entry. Supporting this concept, eHEV infectivity was substantially reduced in cells depleted of Niemann-Pick disease type C1, a lysosomal protein required for cholesterol extraction from lipid, or in cells treated with an inhibitor of lysosomal acid lipase. These data support a model in which the quasi-envelope is degraded within the lysosome prior to virus uncoating, a potentially novel mechanism for virus entry. IMPORTANCE: The recent discovery of quasi-enveloped viruses has shifted the paradigm of virus-host interactions. The impact of quasi envelopment in the virus life cycle and pathogenesis is largely unknown. HEV is a highly relevant model to study these questions. HEV circulates as quasi-enveloped virions in the blood that are hidden from neutralizing antibodies. eHEV particles most likely are responsible for the cell-to-cell spread of the virus. Given the increasing concerns about persistent HEV infection and its potential for transmission via the blood supply, understanding how eHEV infects cells is important for understanding its pathogenesis and developing therapies. Our data provide evidence that eHEV uses a potentially novel mechanism for cellular entry. Several steps critical to eHEV entry were identified and may provide a basis for developing treatments for hepatitis E. Because quasi-enveloped viruses resemble exosomes, these data also may provide insights into the exosome-mediated intercellular communications. PMID- 26865707 TI - Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses. AB - Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options. PMID- 26865709 TI - Impact of Heparan Sulfate Binding on Transduction of Retina by Recombinant Adeno Associated Virus Vectors. AB - Adeno-associated viruses (AAVs) currently are being developed to efficiently transduce the retina following noninvasive, intravitreal (Ivt) injection. However, a major barrier encountered by intravitreally delivered AAVs is the inner limiting membrane (ILM), a basement membrane rich in heparan sulfate (HS) proteoglycan. The goal of this study was to determine the impact of HS binding on retinal transduction by Ivt-delivered AAVs. The heparin affinities of AAV2-based tyrosine-to-phenylalanine (Y-F) and threonine-to-valine (T-V) capsid mutants, designed to avoid proteasomal degradation during cellular trafficking, were established. In addition, the impact of grafting HS binding residues onto AAV1, AAV5, and AAV8(Y733F) as well as ablation of HS binding by AAV2-based vectors on retinal transduction was investigated. Finally, the potential relationship between thermal stability of AAV2-based capsids and Ivt-mediated transduction was explored. The results show that the Y-F and T-V AAV2 capsid mutants bind heparin but with slightly reduced affinity relative to that of AAV2. The grafting of HS binding increased Ivt transduction by AAV1 but not by AAV5 or AAV8(Y733F). The substitution of any canonical HS binding residues ablated Ivt-mediated transduction by AAV2-based vectors. However, these same HS variant vectors displayed efficient retinal transduction when delivered subretinally. Notably, a variant devoid of canonical HS binding residues, AAV2(4pMut)DeltaHS, was remarkably efficient at transducing photoreceptors. The disparate AAV phenotypes indicate that HS binding, while critical for AAV2-based vectors, is not the sole determinant for transduction via the Ivt route. Finally, Y-F and T-V mutations alter capsid stability, with a potential relationship existing between stability and improvements in retinal transduction by Ivt injection. IMPORTANCE: AAV has emerged as the vector of choice for gene delivery to the retina, with attention focused on developing vectors that can mediate transduction following noninvasive, intravitreal injection. HS binding has been postulated to play a role in intravitreally mediated transduction of retina. Our evaluation of the HS binding of AAV2-based variants and other AAV serotype vectors and the correlation of this property with transduction points to HS affinity as a factor controlling retinal transduction following Ivt delivery. However, HS binding is not the only requirement for improved Ivt-mediated transduction. We show that AAV2-based vectors lacking heparin binding transduce retina by subretinal injection and display a remarkable ability to transduce photoreceptors, indicating that other receptors are involved in this phenotype. PMID- 26865711 TI - Hepatitis B Virus Infection of a Mouse Hepatic Cell Line Reconstituted with Human Sodium Taurocholate Cotransporting Polypeptide. AB - Hepatitis B virus (HBV) enters hepatocytes via its receptor, human sodium taurocholate cotransporting polypeptide (hNTCP). So far, HBV infection has been achieved only in human hepatic cells reconstituted with hNTCP and not in cells of mouse origin. Here, the first mouse liver cell line (AML12) which gains susceptibility to HBV upon hNTCP expression is described. Thus, HBV infection of receptor-expressing mouse hepatocytes does not principally require a human cofactor but can be triggered by endogenous murine determinants. PMID- 26865710 TI - SUN2 Overexpression Deforms Nuclear Shape and Inhibits HIV. AB - In a previous screen of putative interferon-stimulated genes, SUN2 was shown to inhibit HIV-1 infection in an uncharacterized manner. SUN2 is an inner nuclear membrane protein belonging to the linker of nucleoskeleton and cytoskeleton complex. We have analyzed here the role of SUN2 in HIV infection. We report that in contrast to what was initially thought, SUN2 is not induced by type I interferon, and that SUN2 silencing does not modulate HIV infection. However, SUN2 overexpression in cell lines and in primary monocyte-derived dendritic cells inhibits the replication of HIV but not murine leukemia virus or chikungunya virus. We identified HIV-1 and HIV-2 strains that are unaffected by SUN2, suggesting that the effect is specific to particular viral components or cofactors. Intriguingly, SUN2 overexpression induces a multilobular flower-like nuclear shape that does not impact cell viability and is similar to that of cells isolated from patients with HTLV-I-associated adult T-cell leukemia or with progeria. Nuclear shape changes and HIV inhibition both mapped to the nucleoplasmic domain of SUN2 that interacts with the nuclear lamina. This block to HIV replication occurs between reverse transcription and nuclear entry, and passaging experiments selected for a single-amino-acid change in capsid (CA) that leads to resistance to overexpressed SUN2. Furthermore, using chemical inhibition or silencing of cyclophilin A (CypA), as well as CA mutant viruses, we implicated CypA in the SUN2-imposed block to HIV infection. Our results demonstrate that SUN2 overexpression perturbs both nuclear shape and early events of HIV infection. IMPORTANCE: Cells encode proteins that interfere with viral replication, a number of which have been identified in overexpression screens. SUN2 is a nuclear membrane protein that was shown to inhibit HIV infection in such a screen, but how it blocked HIV infection was not known. We show that SUN2 overexpression blocks the infection of certain strains of HIV before nuclear entry. Mutation of the viral capsid protein yielded SUN2-resistant HIV. Additionally, the inhibition of HIV infection by SUN2 involves cyclophilin A, a protein that binds the HIV capsid and directs subsequent steps of infection. We also found that SUN2 overexpression substantially changes the shape of the cell's nucleus, resulting in many flower-like nuclei. Both HIV inhibition and deformation of nuclear shape required the domain of SUN2 that interacts with the nuclear lamina. Our results demonstrate that SUN2 interferes with HIV infection and highlight novel links between nuclear shape and viral infection. PMID- 26865712 TI - Two Novel DNAs That Enhance Symptoms and Overcome CMD2 Resistance to Cassava Mosaic Disease. AB - Cassava mosaic begomoviruses (CMBs) cause cassava mosaic disease (CMD) across Africa and the Indian subcontinent. Like all members of the geminivirus family, CMBs have small, circular single-stranded DNA genomes. We report here the discovery of two novel DNA sequences, designated SEGS-1 and SEGS-2 (forsequencesenhancinggeminivirussymptoms), that enhance symptoms and break resistance to CMD. The SEGS are characterized by GC-rich regions and the absence of long open reading frames. Both SEGS enhanced CMD symptoms in cassava (Manihot esculentaCrantz) when coinoculated withAfrican cassava mosaic virus(ACMV),East African cassava mosaic Cameroon virus(EACMCV), orEast African cassava mosaic virus-Uganda(EACMV-UG). SEGS-1 also overcame resistance of a cassava landrace carrying the CMD2 resistance locus when coinoculated with EACMV-UG. Episomal forms of both SEGS were detected in CMB-infected cassava but not in healthy cassava. SEGS-2 episomes were also found in virions and whiteflies. SEGS-1 has no homology to geminiviruses or their associated satellites, but the cassava genome contains a sequence that is 99% identical to full-length SEGS-1. The cassava genome also includes three sequences with 84 to 89% identity to SEGS-2 that together encompass all of SEGS-2 except for a 52-bp region, which includes the episomal junction and a 26-bp sequence related to alphasatellite replication origins. These results suggest that SEGS-1 is derived from the cassava genome and facilitates CMB infection as an integrated copy and/or an episome, while SEGS-2 was originally from the cassava genome but now is encapsidated into virions and transmitted as an episome by whiteflies. IMPORTANCE: Cassava is a major crop in the developing world, with its production in Africa being second only to maize. CMD is one of the most important diseases of cassava and a serious constraint to production across Africa. CMD2 is a major CMD resistance locus that has been deployed in many cassava cultivars through large-scale breeding programs. In recent years, severe, atypical CMD symptoms have been observed occasionally on resistant cultivars, some of which carry the CMD2 locus, in African fields. In this report, we identified and characterized two DNA sequences, SEGS-1 and SEGS 2, which produce similar symptoms when coinoculated with cassava mosaic begomoviruses onto a susceptible cultivar or a CMD2-resistant landrace. The ability of SEGS-1 to overcome CMD2 resistance and the transmission of SEGS-2 by whiteflies has major implications for the long-term durability of CMD2 resistance and underscore the need for alternative sources of resistance in cassava. PMID- 26865713 TI - Transient CD4+ T Cell Depletion Results in Delayed Development of Functional Vaccine-Elicited Antibody Responses. AB - We have recently demonstrated that CD4(+)T cell help is required at the time of adenovirus (Ad) vector immunization for the development of functional CD8(+)T cell responses, but the temporal requirement for CD4(+)T cell help for the induction of antibody responses remains unclear. Here we demonstrate that induction of antibody responses in C57BL/6 mice can occur at a time displaced from the time of Ad vector immunization by depletion of CD4(+)T cells. Transient depletion of CD4(+)T cells at the time of immunization delays the development of antigen-specific antibody responses but does not permanently impair their development or induce tolerance against the transgene. Upon CD4(+)T cell recovery, transgene-specific serum IgG antibody titers develop and reach a concentration equivalent to that in undepleted control animals. These delayed antibody responses exhibit no functional defects with regard to isotype, functional avidity, expansion after boosting immunization, or the capacity to neutralize a simian immunodeficiency virus (SIV) Env-expressing pseudovirus. The development of this delayed transgene-specific antibody response is temporally linked to the expansion of de novo antigen-specific CD4(+)T cell responses, which develop after transient depletion of CD4(+)T cells. These data demonstrate that functional vaccine-elicited antibody responses can be induced even if CD4(+)T cell help is provided at a time markedly separated from the time of vaccination. IMPORTANCE: CD4(+)T cells have a critical role in providing positive help signals to B cells, which promote robust antibody responses. The paradigm is that helper signals must be provided immediately upon antigen exposure, and their absence results in tolerance against the antigen. Here we demonstrate that, in contrast to the current model that the absence of CD4(+)T cell help at priming results in long-term antibody nonresponsiveness, antibody responses can be induced by adenovirus vector immunization or alum-adjuvanted protein immunization even if CD4(+)T cell help is not provided until >1 month after immunization. These data demonstrate that the time when CD4(+)T cell help signals must be provided is more dynamic and flexible than previously appreciated. These data suggest that augmentation of CD4(+)T cell helper function even after the time of vaccination can enhance vaccine-elicited antibody responses and thereby potentially enhance the immunogenicity of vaccines in immunocompromised individuals. PMID- 26865714 TI - Role of TSPAN9 in Alphavirus Entry and Early Endosomes. AB - Alphaviruses are small enveloped RNA viruses that infect cells via clathrin mediated endocytosis and low-pH-triggered fusion in the early endosome. Using a small interfering RNA (siRNA) screen in human cells, we previously identified TSPAN9 as a host factor that promotes infection by the alphaviruses Sindbis virus (SINV), Semliki Forest virus (SFV), and chikungunya virus (CHIKV). Depletion of TSPAN9 specifically decreases SFV membrane fusion in endosomes. TSPAN9 is a member of the tetraspanin family of multipass membrane proteins, but its cellular function is currently unknown. Here we used U-2 OS cells stably overexpressing TSPAN9 to show that TSPAN9 is localized at the plasma membrane and in early and late endosomes. Internalized SFV particles colocalized with TSPAN9 in vesicles early during infection. Depletion of TSPAN9 led to reductions in the amounts of the late endosomal proteins LAMP1 and CD63 and an increase in the amount of LAMP2. However, TSPAN9 depletion did not alter the delivery of SFV to early endosomes or change their pH or protease activity. Comparative studies showed that TSPAN9 depletion strongly inhibited infection by several viruses that fuse in early endosomes (SFV, SINV, CHIKV, and vesicular stomatitis virus [VSV]), while viruses that fuse in the late endosome (recombinant VSV-Lassa and VSV Junin), including an SFV point mutant with a lower pH threshold for fusion (SFV E2 T12I), were relatively resistant. Our data suggest that TSPAN9 modulates the early endosome compartment to make it more permissive for membrane fusion of early-penetrating viruses. IMPORTANCE: Alphaviruses are spread by mosquitoes and can cause serious human diseases such as arthritis and encephalitis. Recent outbreaks of CHIKV infection are responsible for millions of cases of acute illness and long-term complications. There are no vaccines or antiviral treatments for these important human pathogens. Alphaviruses infect host cells by utilizing the endocytic machinery of the cell and fusing their membrane with that of the endosome. Although the mechanism of virus-membrane fusion is well studied, we still know relatively little about the host cell proteins that are involved in alphavirus entry. Here we characterized the role of the host membrane protein TSPAN9 in alphavirus infection. TSPAN9 was localized to early endosomes containing internalized alphavirus, and depletion of TSPAN9 inhibited virus fusion with the early endosome membrane. In contrast, infection of viruses that enter through the late endosome was relatively resistant to TSPAN9 depletion, suggesting an important role for TSPAN9 in the early endosome. PMID- 26865715 TI - Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice. AB - Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies ofMus musculus Receptor usage and envelope (env) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions ofenvproduced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome.envvariations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline rich region ofenv Outside theenvregion, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributedMussubspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents. IMPORTANCE: Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution. PMID- 26865716 TI - MicroRNA-Detargeted Mengovirus for Oncolytic Virotherapy. AB - Mengovirus, a member of thePicornaviridaefamily, has a broad cell tropism and can cause encephalitis and myocarditis in multiple mammalian species. Attenuation has been achieved by shortening the polycytidine tract in the 5' noncoding region (NCR). A poly(C)-truncated strain of mengovirus, vMC24, resulted in significant tumor regression in immunocompetent BALB/c mice bearing syngeneic MPC-11 plasmacytomas, but the associated toxicities were unacceptable. To enhance its safety profile, microRNA target sequences complementary to miR-124 or miR-125 (enriched in nervous tissue), miR-133 and miR-208 (enriched in cardiac tissue), or miR-142 (control; enriched in hematopoietic tissues) were inserted into the vMC24NCRs. The microRNA-detargeted viruses showed reduced replication and cell killing specifically in cells expressing the cognate microRNAs, but certain insertions additionally were associated with nonspecific suppression of viral fitnessin vivo. In vivotoxicity testing confirmed that miR-124 targets within the 5' NCR suppressed virus replication in the central nervous system while miR-133 and miR-208 targets in the 3' NCR suppressed viral replication in cardiac tissue. A dual-detargeted virus named vMC24-NC, with miR-124 targets in the 5' NCR and miR-133 plus miR-208 targets in the 3' NCR, showed the suppression of replication in both nervous and cardiac tissues but retained full oncolytic potency when administered by intratumoral (10(6)50% tissue culture infectious doses [TCID50]) or intravenous (10(7)to 10(8)TCID50) injection into BALB/c mice bearing MPC-11 plasmacytomas. Overall survival of vMC24-NC-treated tumor-bearing mice was significantly improved compared to that of nontreated mice. MicroRNA-detargeted mengoviruses offer a promising oncolytic virotherapy platform that merits further development for clinical translation. IMPORTANCE: The clinical potential of oncolytic virotherapy for cancer treatment has been well demonstrated, justifying the continued development of novel oncolytic viruses with enhanced potency. Here, we introduce mengovirus as a novel oncolytic agent. Mengovirus is appealing as an oncolytic virotherapy platform because of its small size, simple genome structure, rapid replication cycle, and broad cell/species tropism. However, mengovirus can cause encephalomyelitis and myocarditis. It can be partially attenuated by shortening the poly(C) tract in the 5' NCR but remains capable of damaging cardiac and nervous tissue. Here, we further enhanced the safety profile of a poly(C)-truncated mengovirus by incorporating muscle- and neuron-specific microRNA target sequences into the viral genome. This dual-detargeted virus has reduced pathogenesis but retained potent oncolytic activity. Our data show that microRNA targeting can be used to further increase the safety of an attenuated mengovirus, providing a basis for its development as an oncolytic platform. PMID- 26865717 TI - Inhibition of the FACT Complex Reduces Transcription from the Human Cytomegalovirus Major Immediate Early Promoter in Models of Lytic and Latent Replication. AB - The successful colonization of the majority of the population by human cytomegalovirus is a direct result of the virus's ability to establish and, more specifically, reactivate from latency. The underlying cellular factors involved in viral reactivation remain unknown. Here, we show that the host complexfacilitateschromatintranscription (FACT) binds to the major immediate early promoter (MIEP) and that inhibition of this complex reduces MIEP transactivation, thus inhibiting viral reactivation. PMID- 26865718 TI - Digging through the Obstruction: Insight into the Epithelial Cell Response to Respiratory Virus Infection in Patients with Cystic Fibrosis. AB - Respiratory virus infections are common but generally self-limiting infections in healthy individuals. Although early clinical studies reported low detection rates, the development of molecular diagnostic techniques by PCR has led to an increased recognition that respiratory virus infections are associated with morbidity and acute exacerbations of chronic lung diseases, such as cystic fibrosis (CF). The airway epithelium is the first barrier encountered by respiratory viruses following inhalation and the primary site of respiratory viral replication. Here, we describe how the airway epithelial response to respiratory viral infections contributes to disease progression in patients with CF and other chronic lung diseases, including the role respiratory viral infections play in bacterial acquisition in the CF patient lung. PMID- 26865720 TI - The Autographa californica Multiple Nucleopolyhedrovirus ac54 Gene Is Crucial for Localization of the Major Capsid Protein VP39 at the Site of Nucleocapsid Assembly. AB - Baculovirus DNAs are synthesized and inserted into preformed capsids to form nucleocapsids at a site in the infected cell nucleus, termed the virogenic stroma. Nucleocapsid assembly ofAutographa californicamultiple nucleopolyhedrovirus (AcMNPV) requires the major capsid protein VP39 and nine minor capsid proteins, including VP1054. However, how VP1054 participates in nucleocapsid assembly remains elusive. In this study, the VP1054-encoding gene (ac54) was deleted to generate theac54-knockout AcMNPV (vAc54KO). In vAc54KO transfected cells, nucleocapsid assembly was disrupted, leading to the formation of abnormally elongated capsid structures. Interestingly, unlike cells transfected with AcMNPV mutants lacking other minor capsid proteins, in which capsid structures were distributed within the virogenic stroma,ac54ablation resulted in a distinctive location of capsid structures and VP39 at the periphery of the nucleus. The altered distribution pattern of capsid structures was also observed in cells transfected with AcMNPV lacking BV/ODV-C42 or in cytochalasind treated AcMNPV-infected cells. BV/ODV-C42, along with PP78/83, has been shown to promote nuclear filamentous actin (F-actin) formation, which is another requisite for nucleocapsid assembly. Immunofluorescence using phalloidin indicated that the formation and distribution of nuclear F-actin were not affected byac54deletion. However, immunoelectron microscopy revealed that BV/ODV-C42, PP78/83, and 38K failed to integrate into capsid structures in the absence of VP1054, and immunoprecipitation further demonstrated that in transient expression assays, VP1054 interacted with BV/ODV-C42 and VP80 but not VP39. Our findings suggest that VP1054 plays an important role in the transport of capsid proteins to the nucleocapsid assembly site prior to the process of nucleocapsid assembly. IMPORTANCE: Baculoviruses are large DNA viruses whose replication occurs within the host nucleus. The localization of capsids into the capsid assembly site requires virus-induced nuclear F-actin; the inhibition of nuclear F-actin formation results in the retention of capsid structures at the periphery of the nucleus. In this paper, we note that the minor capsid protein VP1054 is essential for the localization of capsid structures, the major capsid protein VP39, and the minor capsid protein 38K into the capsid assembly site. Moreover, VP1054 is crucial for correct targeting of the nuclear F-actin factors BV/ODV-C42 and PP78/83 for capsid maturation. However, the formation and distribution of nuclear F-actin are not affected by the lack of VP1054. We further reveal that VP1054 interacts with BV/ODV-C42 and a capsid transport-related protein, VP80. Taken together, our findings suggest that VP1054 plays a unique role in the pathway(s) for transport of capsid proteins. PMID- 26865719 TI - Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens. AB - In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8(+)and CD4(+)T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE: Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols. PMID- 26865721 TI - The RNA- and TRIM25-Binding Domains of Influenza Virus NS1 Protein Are Essential for Suppression of NLRP3 Inflammasome-Mediated Interleukin-1beta Secretion. AB - Inflammasomes are cytosolic multimolecular protein complexes that stimulate the activation of caspase-1 and the release of mature forms of interleukin-1beta (IL 1beta) and IL-18. We previously demonstrated that the influenza A virus M2 protein stimulates IL-1beta secretion following activation of the nucleotide binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The nonstructural protein 1 (NS1) of influenza virus inhibits caspase-1 activation and IL-1beta secretion. However, the precise mechanism by which NS1 inhibits IL-1beta secretion remains unknown. Here, we showed that J774A.1 macrophages stably expressing the NS1 protein inhibited IL 1beta secretion after infection with recombinant influenza virus lacking the NS1 gene. Coimmunoprecipitation assay revealed that the NS1 protein interacts with NLRP3. Importantly, the NS1 protein inhibited the NLRP3/ASC-induced single-speck formation required for full activation of inflammasomes. The NS1 protein of other influenza virus strains, including a recent pandemic strain, also inhibited inflammasome-mediated IL-1beta secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) were required for suppression of NLRP3 inflammasome-mediated IL-1beta secretion. These results shed light on a mechanism by which the NS1 protein of influenza virus suppresses NLRP3 inflammasome-mediated IL-1beta secretion. IMPORTANCE: Innate immune sensing of influenza virus via pattern recognition receptors not only plays a key role in generating type I interferons but also triggers inflammatory responses. We previously demonstrated that the influenza A virus M2 protein activates the NLRP3 inflammasome, leading to the secretion of interleukin-1beta (IL-1beta) and IL-18 following the activation of caspase-1. Although the nonstructural protein 1 (NS1) of influenza virus inhibits IL-1beta secretion, the precise mechanism by which it achieves this remains to be defined. Here, we demonstrate that the NS1 protein interacts with NLRP3 to suppress NLRP3 inflammasome activation. J774A.1 macrophages stably expressing the NS1 protein suppressed NLRP3-mediated IL-1beta secretion. The NS1 RNA-binding domain (basic residues 38 and 41) and TRIM25-binding domain (acidic residues 96 and 97) are important for suppression of NLRP3 inflammasome-mediated IL-1beta secretion. These results will facilitate the development of new anti-inflammatory drugs. PMID- 26865722 TI - The Low-pH Resistance of Neuraminidase Is Essential for the Replication of Influenza A Virus in Duck Intestine following Infection via the Oral Route. AB - Influenza A viruses are known to primarily replicate in duck intestine following infection via the oral route, but the specific role of neuraminidase (NA) for the intestinal tropism of influenza A viruses has been unclear. A reassortant virus (Dk78/Eng62N2) did not propagate in ducks infected via the oral route. To generate variant viruses that grow well in ducks via the oral route, we isolated viruses that effectively replicate in intestinal mucosal cells by passaging Dk78/Eng62N2 in duck via rectal-route infection. This procedure led to the isolation of a variant virus from the duck intestine. This virus was propagated using embryonated chicken eggs and inoculated into a duck via the oral route, which led to the isolation of Dk-rec6 from the duck intestine. Experimental infections with mutant viruses generated by using reverse genetics indicated that the paired mutation of residues 356 and 431 in NA was necessary for the viral replication in duck intestine. The NA assay revealed that the activity of Dk78/Eng62N2 almost disappeared after pH 3 treatment, whereas that of Dk-rec6 was maintained. Furthermore, to identify the amino acid residues associated with the low-pH resistance, we measured the activities of mutant NA proteins transiently expressed in 293 cells after pH 3 treatment. All mutant NA proteins that possessed proline at position 431 showed higher activities than NA proteins that possessed glutamine at this position. These findings indicate that the low-pH resistance of NA plays an important role in the ability of influenza A virus to replicate in duck intestine. IMPORTANCE: Neuraminidase (NA) activity facilitates the release of viruses from cells and, as such, is important for the replicative efficiency of influenza A virus. Ducks are believed to serve as the principal natural reservoir for influenza A virus; however, the key properties of NA for viral infection in duck are not well understood. In this study, we identify amino acid residues in NA that contribute to viral replication in ducks via the natural route of infection and demonstrate that maintenance of NA activity under low-pH conditions is associated with the biological properties of the virus. These findings provide insights into the mechanisms of replication of influenza A virus in ducks. PMID- 26865723 TI - Effects of an In-Frame Deletion of the 6k Gene Locus from the Genome of Ross River Virus. AB - The alphaviral6kgene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the6kproteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel6kin-frame deletion mutant. Comprehensive microscopic analysis revealed that the6kproteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the6kproteins 6K and TF [RRV-(Delta6K)] were more vulnerable to changes in pH, and the corresponding virus had increased sensitivity to a higher temperature. While the6kdeletion did not reduce RRV particle production in BHK-21 cells, it affected virion release from the host cell. Subsequentin vivostudies demonstrated that RRV-(Delta6K) caused a milder disease than wild-type virus, with viral titers being reduced in infected mice. Immunization of mice with RRV (Delta6K) resulted in a reduced viral load and accelerated viral elimination upon secondary infection with wild-type RRV or another alphavirus, chikungunya virus (CHIKV). Our results show that the6kproteins may contribute to alphaviral disease manifestations and suggest that manipulation of the6kgene may be a potential strategy to facilitate viral vaccine development. IMPORTANCE: Arthritogenic alphaviruses, such as chikungunya virus (CHIKV) and Ross River virus (RRV), cause epidemics of debilitating rheumatic disease in areas where they are endemic and can emerge in new regions worldwide. RRV is of considerable medical significance in Australia, where it is the leading cause of arboviral disease. The mechanisms by which alphaviruses persist and cause disease in the host are ill defined. This paper describes the phenotypic properties of an RRV6kdeletion mutant. The absence of the6kgene reduced virion release from infected cells and also reduced the severity of disease and viral titers in infected mice. Immunization with the mutant virus protected mice against viremia not only upon exposure to RRV but also upon challenge with CHIKV. These findings could lead to the development of safer and more immunogenic alphavirus vectors for vaccine delivery. PMID- 26865724 TI - Hepatitis C Virus-Induced Degradation of Cell Death-Inducing DFFA-Like Effector B Leads to Hepatic Lipid Dysregulation. AB - Individuals chronically infected with hepatitis C virus (HCV) commonly exhibit hepatic intracellular lipid accumulation, termed steatosis. HCV infection perturbs host lipid metabolism through both cellular and virus-induced mechanisms, with the viral core protein playing an important role in steatosis development. We have recently identified a liver protein, the cell death-inducing DFFA-like effector B (CIDEB), as an HCV entry host dependence factor that is downregulated by HCV infection in a cell culture model. In this study, we investigated the biological significance and molecular mechanism of this downregulation. HCV infection in a mouse model downregulated CIDEB in the liver tissue, and knockout of the CIDEB gene in a hepatoma cell line results in multiple aspects of lipid dysregulation that can contribute to hepatic steatosis, including reduced triglyceride secretion, lower lipidation of very-low-density lipoproteins, and increased lipid droplet (LD) stability. The potential link between CIDEB downregulation and steatosis is further supported by the requirement of the HCV core and its LD localization for CIDEB downregulation, which utilize a proteolytic cleavage event that is independent of the cellular proteasomal degradation of CIDEB. IMPORTANCE: Our data demonstrate that HCV infection of human hepatocytesin vitroandin vivoresults in CIDEB downregulation via a proteolytic cleavage event. Reduction of CIDEB protein levels by HCV or gene editing, in turn, leads to multiple aspects of lipid dysregulation, including LD stabilization. Consequently, CIDEB downregulation may contribute to HCV-induced hepatic steatosis. PMID- 26865725 TI - Porcine Sapelovirus Uses alpha2,3-Linked Sialic Acid on GD1a Ganglioside as a Receptor. AB - The receptor(s) for porcine sapelovirus (PSV), which causes diarrhea, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs, remains largely unknown. Given the precedent for other picornaviruses which use terminal sialic acids (SAs) as receptors, we examined the role of SAs in PSV binding and infection. Using a variety of approaches, including treating cells with a carbohydrate-destroying chemical (NaIO4), mono- or oligosaccharides (N acetylneuraminic acid, galactose, and 6'-sialyllactose), linkage-specific sialidases (neuraminidase and sialidase S), lectins (Maakia amurensislectin andSambucus nigralectin), proteases (trypsin and chymotrypsin), and glucosylceramide synthase inhibitors (dl-threo-1-phenyl-2-decanoylamino-3 morpholino-1-propanol and phospholipase C), we demonstrated that PSV could recognize alpha2,3-linked SA on glycolipids as a receptor. On the other hand, PSVs had no binding affinity for synthetic histo-blood group antigens (HBGAs), suggesting that PSVs could not use HBGAs as receptors. Depletion of cell surface glycolipids followed by reconstitution studies indicated that GD1a ganglioside, but not other gangliosides, could restore PSV binding and infection, further confirming alpha2,3-linked SA on GD1a as a PSV receptor. Our results could provide significant information on the understanding of the life cycle of sapelovirus and other picornaviruses. For the broader community in the area of pathogens and pathogenesis, these findings and insights could contribute to the development of affordable, useful, and efficient drugs for anti-sapelovirus therapy. IMPORTANCE: The porcine sapelovirus (PSV) is known to cause enteritis, pneumonia, polioencephalomyelitis, and reproductive disorders in pigs. However, the receptor(s) that the PSV utilizes to enter host cells remains largely unknown. Using a variety of approaches, we showed that alpha2,3-linked terminal sialic acid (SA) on the cell surface GD1a ganglioside could be used for PSV binding and infection as a receptor. On the other hand, histo-blood group antigens also present in the cell surface carbohydrates could not be utilized as PSV receptors for binding and infection. These findings should contribute to the understanding of the sapelovirus life cycle and to the development of affordable, useful and efficient drugs for anti-sapelovirus therapy. PMID- 26865731 TI - A partial loss-of-function mutation in an Arabidopsis RNA polymerase III subunit leads to pleiotropic defects. AB - Plants employ five DNA-dependent RNA polymerases (Pols) in transcription. One of these polymerases, Pol III, has previously been reported to transcribe 5S rRNA, tRNAs, and a number of small RNAs. However, in-depth functional analysis is complicated by the fact that knockout mutations in Pol subunits are typically lethal. Here, we report the characterization of the first known viable Pol III subunit mutant,nrpc7-1 This mutant was originally isolated from a forward genetic screen designed to identify enhancers of the autoimmune mutantsnc1, which contains a gain-of-function mutation in a nucleotide-binding leucine-rich repeat (NLR) immune receptor-encoding gene. Thenrpc7-1mutation occurs in an intron-exon splice site and results in intron retention in someNRPC7transcripts. There is a global disruption in RNA equilibrium innrpc7-1, exemplified by the altered expression of a number of RNA molecules, some of which are not reported to be transcribed by Pol III. There are developmental defects associated with the mutation, as homozygous mutant plants are dwarf, have stunted roots and siliques, and possess serrated leaves. These defects are possibly due to altered small RNA stability or activity. Additionally, thenrpc7-1mutation confers anNLR-specific alternative splicing defect that correlates with enhanced disease resistance, highlighting the importance of alternative splicing in regulating NLR activity. Altogether, these results reveal novel roles for Pol III in maintaining RNA homeostasis, adjusting the expression of a diverse suite of genes, and indirectly modulating gene splicing. Future analyses using thenrpc7-1mutant will be instrumental in examining other unknown Pol III functions. PMID- 26865732 TI - Genome-Wide Association Study in Arabidopsis thaliana of Natural Variation in Seed Oil Melting Point: A Widespread Adaptive Trait in Plants. AB - Seed oil melting point is an adaptive, quantitative trait determined by the relative proportions of the fatty acids that compose the oil. Micro- and macro evolutionary evidence suggests selection has changed the melting point of seed oils to covary with germination temperatures because of a trade-off between total energy stores and the rate of energy acquisition during germination under competition. The seed oil compositions of 391 natural accessions of Arabidopsis thaliana, grown under common-garden conditions, were used to assess whether seed oil melting point within a species varied with germination temperature. In support of the adaptive explanation, long-term monthly spring and fall field temperatures of the accession collection sites significantly predicted their seed oil melting points. In addition, a genome-wide association study (GWAS) was performed to determine which genes were most likely responsible for the natural variation in seed oil melting point. The GWAS found a single highly significant association within the coding region of FAD2, which encodes a fatty acid desaturase central to the oil biosynthesis pathway. In a separate analysis of 15 a priori oil synthesis candidate genes, 2 (FAD2 and FATB) were located near significant SNPs associated with seed oil melting point. These results comport with others' molecular work showing that lines with alterations in these genes affect seed oil melting point as expected. Our results suggest natural selection has acted on a small number of loci to alter a quantitative trait in response to local environmental conditions. PMID- 26865733 TI - Regional Genetic Structure and Environmental Variables Influence our Conservation Approach for Feather Heads (Ptilotus macrocephalus). AB - Continued alterations to the Australian environment compromise the long-term viability of many plant species. We investigate the population genetics of Ptilotus macrocephalus, a perennial herb that occurs in 2 nationally endangered communities on the Victorian Volcanic Plain Bioregion (VVP), Australia, to answer key questions regarding regional differentiation and to guide conservation strategies. We evaluate genetic structure and diversity within and among 17 P. macrocephalus populations from 3 regions of southeastern Australia using 17 microsatellite markers developed de novo. Genetic structure was present in P. macrocephalus between the 3 regions but not at the population level. Environmental factors, namely temperature and precipitation, significantly explained differentiation between the North region and the other 2 regions indicating isolation by environment. Within regions, genetic structure currently shows a high level of gene flow and genetic variation. Our results suggest that within-region gene flow does not reflect current habitat fragmentation in southeastern Australia whereas temperature and precipitation are likely to be responsible for the differentiation detected among regions. Climate change may severely impact P. macrocephalus on the VVP and test its evolutionary resilience. We suggest taking a proactive conservation approach to improve long-term viability by sourcing material for restoration to assist gene flow to the VVP region to promote an increased adaptive capacity. PMID- 26865734 TI - Broadly tunable, low timing jitter, high repetition rate optoelectronic comb generator. AB - We investigate the low timing jitter properties of a tunable single-pass optoelectronic frequency comb generator. The scheme is flexible in that both the repetition rate and center frequency can be continuously tuned. When operated with 10 GHz comb spacing, the integrated residual pulse-to-pulse timing jitter is 11.35 fs (1 Hz to 10 MHz) with no feedback stabilization. The corresponding phase noise at 1 Hz offset from the photodetected 10 GHz carrier is -100 dBc/Hz. PMID- 26865735 TI - Local error estimates for adaptive simulation of the Reaction-Diffusion Master Equation via operator splitting. AB - The efficiency of exact simulation methods for the reaction-diffusion master equation (RDME) is severely limited by the large number of diffusion events if the mesh is fine or if diffusion constants are large. Furthermore, inherent properties of exact kinetic-Monte Carlo simulation methods limit the efficiency of parallel implementations. Several approximate and hybrid methods have appeared that enable more efficient simulation of the RDME. A common feature to most of them is that they rely on splitting the system into its reaction and diffusion parts and updating them sequentially over a discrete timestep. This use of operator splitting enables more efficient simulation but it comes at the price of a temporal discretization error that depends on the size of the timestep. So far, existing methods have not attempted to estimate or control this error in a systematic manner. This makes the solvers hard to use for practitioners since they must guess an appropriate timestep. It also makes the solvers potentially less efficient than if the timesteps are adapted to control the error. Here, we derive estimates of the local error and propose a strategy to adaptively select the timestep when the RDME is simulated via a first order operator splitting. While the strategy is general and applicable to a wide range of approximate and hybrid methods, we exemplify it here by extending a previously published approximate method, the Diffusive Finite-State Projection (DFSP) method, to incorporate temporal adaptivity. PMID- 26865736 TI - Local reaction kinetics by imaging. AB - In the present contribution we present an overview of our recent studies using the "kinetics by imaging" approach for CO oxidation on heterogeneous model systems. The method is based on the correlation of the PEEM image intensity with catalytic activity: scaled down to the MUm-sized surface regions, such correlation allows simultaneous local kinetic measurements on differently oriented individual domains of a polycrystalline metal-foil, including the construction of local kinetic phase diagrams. This allows spatially- and component-resolved kinetic studies and, e.g., a direct comparison of inherent catalytic properties of Pt(hkl)- and Pd(hkl)-domains or supported MUm-sized Pd powder agglomerates, studies of the local catalytic ignition and the role of defects and grain boundaries in the local reaction kinetics. PMID- 26865737 TI - Nobel prize, Traditional Chinese Medicine and Lessons for Ayurveda? PMID- 26865738 TI - Therapeutic potential of Polyalthia cerasoides stem bark extracts against oxidative stress and nociception. AB - BACKGROUND: Polyalthia cerasoides is a medicinal plant known for its ethnopharmacological importance. Despite this, investigation related to its therapeutic benefit is still unexplored. AIM: To evaluate the stem bark extracts of Polyalthia cerasoides for pharmacological activities relating to inflammation, nociception and oxidative stress using in vivo and in vitro models. MATERIALS AND METHODS: Pet ether, ethyl acetate and chloroform fractions of the stem bark were evaluated for anti-inflammatory activity by carrageenan-induced hind paw edema in rats. Anti-nociceptive activity in mice was assessed using thermally and chemically induced analgesic models. The free radical quenching potential of the extracts was initially analyzed using the in vitro DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assays. Then modulatory effect of the extracts on in vivo antioxidant system was evaluated by carbon tetrachloride induced hepatotoxicity and subsequent measurements of antioxidant enzymes such as Superoxide dismutase, Catalase and Peroxidase from the liver homogenate. RESULTS: Among the tested fractions, ethyl acetate extract had substantially inhibited the inflammation by 68.5% that was induced by subcutaneous carrageenan injection whereas pet ether and chloroform extract showed only minimal inhibitory effect. Investigation of the anti-nociceptive activity revealed that the ethyl acetate fractions had significantly repressed the algesia in both the analgesic experimental models. In vitro and in vivo individual antioxidant assays demonstrated that the ethyl acetate fraction has strong free radical quenching potential which also restores the endogenous hepatic enzymes. CONCLUSION: The ethyl acetate fraction enriched with flavinoids and steroids from Polyalthia cerasoides stem bark has potent bioactivity to combat inflammation, ROS and pain. This needs further characterization for potential therapeutic applications. PMID- 26865739 TI - Cardioprotective role of methanolic extract of bark of Terminalia arjuna against in-vitro model of myocardial ischemic-reperfusion injury. AB - BACKGROUND: The present study was designed to investigate the cardio protective role of chronic oral administration of methanolic extract of Terminalia arjuna bark in in-vitro myocardial ischemic reperfusion injury and the induction of HSP72. MATERIALS AND METHODS: Rats, divided into three groups, and were administered with the methanolic extract of the bark powder of Terminalia arjuna (TAME) by oral gavage (6.75 and 9.75 mg/kg: 6 days/week for 12 weeks). Control and TAME extract treated rat hearts were subjected to in-vitro global ischemic reperfusion injury (5 min perfusion, 9 min noflow and 12 min reperfusion). RESULTS: Oxidative stress in MIRI was evidenced by, raised levels of myocardial TBARS and depletion of endogenous myocardial antioxidants GSH, SOD and catalase. Western blot analysis showed a single band corresponding to 72 kDa in homogenates of hearts from rat treated with both the doses. In the methanolic extract of the bark powder of Terminalia arjuna treatment groups, both the doses had better recovery of myocardial function, with significant reduction in TBARS, and rise in SOD, GSH, catalase were observed. CONCLUSION: The results of the present study suggest that the methanolic extract of the bark powder of Terminalia arjuna in rat induces myocardial HSP72 and augments myocardial endogenous antioxidants, without causing any cellular injury and offers better cardioprotection against oxidative stress associated with myocardial IR injury. PMID- 26865740 TI - Role of quassinoids as potential antimalarial agents: An in silico approach. AB - BACKGROUND: Malaria is an infection caused by mosquitoes in human beings which can be dangerous if untreated. A well known plant product, quassinoids are known to have antimalarial activity. These bioactive phytochemicals belong to the triterpene family. Quassinoids are used in the present study to act against malarial dihydrofolate reductase (Pf-DHFR), a potential antimalarial target. Nevertheless, visama jvara (~malaria) has been treated with the bark of Cinchona since a long time. AIM: The aim of the present experiment is to perform the protein-ligand docking for Pf- DHFR and Quassinoids and study their binding affinities. SETTING AND DESIGN: The software used for the present study is the discovery studio (Accelrys 2.1), Protein Data Bank (PDB), and Chemsketch. MATERIALS AND METHODS: The protein for the present study was imported from protein data bank with the PDB Id, 4dpd and was prepared for docking. The ligands used for the study are the quassinoids. They were drawn using chemsketch and the 3D structures were generated. The docking was done subsequently. STATISTICAL ANALYSIS USED: Molecular modeling technique was used for the protein-ligand docking analysis. RESULTS: The docking results showed that the Quassinoids Model_1 showed the highest dock score of 40.728. CONCLUSION: The present study proves the promising potential of quassinoids as novel drugs against malaria. The dock results conclude that the quassinoids can be adopted as an alternative drug against malaria. PMID- 26865741 TI - Evaluation of the estrogenic activity of Indian medicinal plants in immature rats. AB - INTRODUCTION: The objective of the study was to evaluate the estrogenic activity of four Indian medicinal plants Saraca indica (Si), Symplocos racemosa (Sr), Cyperus rotundus (Cr), Terminalia arjuna (Ta), a marketed preparation of Si (Asokarista) and a combination of Si + Sr using an experimental model of estrogenicity. MATERIALS AND METHODS: After approval of the institutional animal ethics committee, 22 day old female rats (n = 54) were randomly allocated to 9 groups - Group 1 and Group 2: Vehicle controls, Group 3: Ethinyl estradiol, Group 4: Si (270 mg/kg), Group 5: Sr (270 mg/kg), Group 6: Cr (540 mg/kg), Group 7: Ta (270 mg/kg), Group 8: Ashokarishta (4 ml/kg), Group 9: Si + Sr (135 mg/kg). Variables studied were: Body weight, uterine weight, relative uterine weight, presence of vaginal opening, histomorphology of the uterus and total uterine glycogen content. Parametric data were analyzed using one-way ANOVA and the categorical data were analyzed using Chi-square test. RESULTS: All animals in the ethinyl estradiol group showed a significant change in all the variables. None of the individual test drugs, neither the marketed preparation produced change in any of the variables. The plant drug combination also did not produce a change in any of the variables studied except in histomorphology wherein it caused a slight increase in the height of the luminal epithelium of the uterus (P < 0.05 vs. Group 1). CONCLUSION: The plant drugs Si, Sr, Cr, Ta and Asokarista did not demonstrate estrogenic activity in the immature rat model. The plant drug combination Si + Sr showed questionable estrogenic activity which needs to be evaluated in further studies. PMID- 26865742 TI - Shelf-life evaluation of Kamsaharitaki avaleha and its granules: A preliminary study. AB - BACKGROUND: Saviryata-avadhi (shelf life) of different Ayurvedic dosage forms is described in Sarngadharasamhita. Though the concepts have a strong background, we seek to re-evaluate the age old concepts by following current norms. An attempt has been made in the present study to evaluate shelf-life of Kamsaharitaki avaleha and its granules. MATERIALS AND METHODS: Raw materials were procured from Pharmacy, Gujarat Ayurved University, Jamnagar and utilized after proper authentication in pharmacognosy lab. The avaleha and its granules were prepared in the departmental laboratory following classical guidelines and subjected to accelerated stability studies. RESULTS: Both the products were found to be free from microbial contamination. Heavy metals were within the prescribed limit. Changes in physico-chemical profiles at different intervals are insignificant. On extrapolation of the observations, the shelf life of avaleha was found to be18 months and 27 months to the granules. CONCLUSION: Stability of granules was found to be comparatively higher than the avaleha. This observation may be exclusive to Kamsaharitaki avaleha. Studies on other avalehas and their granules need to be carried out to confirm this preliminary observation. PMID- 26865743 TI - Comparative Anti-hyperlipidaemic activity of Navina (fresh) and Purana (old) Guggulu. AB - OBJECTIVE: Guggulu (Commiphora wightii [Arn.] Bhandari) is a well-known anti hyperlipidaemic drug. Guggulsterones are active components of this drug which are responsible for this effect. The activity of Guggulu may depend upon its nature, fresh samples are recommended for their brhmana (body mass increasing) effect; while lekhana (scarificant) effect is attributed to the old one. The comparative Anti-hyperlipidaemic activity of fresh and old samples has not been reported till date. MATERIALS AND METHODS: Freshly collected and one year old samples of Guggulu were processed in gomutra. Patients who satisfied inclusion criteria of Hyperlipidaemia were randomly distributed into two groups and the drug was administrated in a dose of 1 g with luke warm water twice a day for eight weeks. RESULTS: Significant improvement was found in the symptoms of Medoroga and Lipid profile with treatment in both the groups. Fresh sample of Guggulu proved to have a better effect in lowering serum cholesterol (5.76%), triglyceride (17.17%), and very low density lipoprotein VLDL (18.36%) levels while old sample of Guggulu provided mild effect in lowering serum triglyceride (13.64%), VLDL (11.07%) and non-significant increase in serum HDL-cholesterol (0.94%). Old sample of Guggulu also provided significant decreases in body weight (7.69%) and BMI (7.82%). CONCLUSIONS: Old Guggulu showed better effect on body weight, BMI and cardinal symptoms along with significant lipid lowering effect whereas fresh Guggulu showed better result on lipid profile. PMID- 26865744 TI - Antiepileptic and antipsychotic activities of standardized Silajatu (Shilajit) in experimental animals. AB - BACKGROUND: Silajatu (Shilajit; SJ) is claimed in traditional Indian medical practice to be useful in the treatment of nervous disorders, epilepsy and as antistress. AIM: To investigate whether SJ possesses antiepileptic and antipsychotic activities in rodents. MATERIALS AND METHODS: Isonicotinyl hydrazine (INH), pentylenetetrazole (PTZ), apomorphine, phenytoin, diazepam, haloperidol and other chemicals of analytical grade were procured from standard companies. The antiepileptic activity of SJ was assessed using maximal electro shock (MES)-induced seizures in rats, INH and PTZ-induced seizures in mice. The antipsychotic effect of SJ was evaluated using apomorphine-induced climbing and stereotyped behaviours respectively, in mice and rats. SETTINGS AND DESIGNS: SJ (25 and 50 mg/kg, p.o.) was given orally once daily for 15 days in all the rodent models. On the test day, SJ was administered 1 h prior to electric shock or chemical inducers (INH/PTZ/apomorphine) in experimental animals; the animals were then observed for different phases of seizures and psychotic behaviours. In addition, gamma-aminobutyric acid (GABA) content in the brain of rats and mice was estimated in seizure models. STATISTICAL ANALYSIS: The data were expressed as mean +/- standard error of mean. Statistical comparisons were performed by one way ANOVA followed by Tukey's post-test using Graph Pad Prism version 5.0, USA. A P < 0.05 was considered significant. RESULTS AND CONCLUSIONS: SJ pretreatment significantly inhibited the seizures induced by MES, INH and PTZ in a dose dependent manner. Further, SJ augmented brain GABA levels to normal, decreased by INH and PTZ in mice brain. SJ pretreatment also significantly inhibited the climbing and stereotyped behaviours induced by apomorphine. The present data seems to confirm the antiepileptic activity of SJ which may be because of enhancing the GABAergic system. The antipsychotic activity observed may be due to anti-dopaminergic and/or GABA-mimetic actions. PMID- 26865745 TI - Wound healing potential of Pancavalkala formulations in a postfistulectomy wound. AB - Sushruta mentioned sixty measures for management of wounds. Panchavalkal is the combination of five herbs having properties like Shodhana (cleaning) and Ropana (healing) of wounds. Individual drugs and in combination have Kashaya rasa (astringent) dominant and useful in the management of Vrana (wounds) as well as Shotha (inflammations). A 35 years old male patient consulted in Shalya OPD with complaints like discharge per anum, induration and intermittent pain at perianal region since last five years. On inspection external opening was observed at anterior portion 1 O' clock position which was four centimeter away from anal verge. That case was diagnosed as Bhagandara (fistula-in-ano) and was treated with partial fistulectomy and application of Guggulu based Ksharasutra in the remaining tract. The big fistulectomy wound was treated with local application of Panchavalkal ointment daily and simultaneous change of Ksharasutra. The wound was assessed daily for pain, swelling, discharge, size, and shape. The wound healed completely within two and half month with normal scar having good tissue strength. This case demonstrated that post fistulectomy wound can be treated with Panchavalkal ointment. PMID- 26865746 TI - Thai traditional massage: Issues causing possible adverse effects. AB - Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID- 26865747 TI - Efficacy of local application of an Unani formulation in acne vulgaris. AB - BACKGROUND AND OBJECTIVES: Buthur-i-Labaniyya (Acne vulgaris) is affecting up to 80% of adolescents and many adults at different stages of life. It is one of the commonest skin disorders which appears on cheeks and nose as white eruptions that seems like solidified milk drops. These eruptions are treated by drugs having properties of tajfif wa tahlil (desiccant and resolving), as mentioned by Ibne Sina. Daood Antaki in his book Tazkira Oolulalbab recommends the local application of a paste of Shoniz (nigella sativa), Naushadar (ammonium chloride) and Bura Armani mixed with Sirka (vinegar) for effective treatment of Acne vulgaris. METHODS: The study was observational self comparison before and after treatment, conducted in the OPD of the hospital which is part of the National Institute of Unani Medicine, Bangalore. The duration of study was one year. 40 Female patients with combination of comedones, papules, pustules and nodules were recruited for this purpose. The test drug, Shoniz, Bura Armani, Naushadar powder, mixed with sirka were applied locally for one month with taqlil-i-ghidha tadabir (low calorie index diet). All subjects were assessed on the basis of changes in subjective and objective parameters. RESULTS: The response of test drugs was statistically highly significant (P < 0.01) by using ANOVA repeated measure test, there was also relief in subjective parameters. Subjects reported a reduction of 82.6%, 80.9%, 66.6% in tenderness, itching and irritation respectively. INTERPRETATION AND CONCLUSION: The present study reveals that the test drug formulation is safe and effective in treating Acne vulgaris if used along with low calorie index diet. No side effects of drugs were reported, therefore the trial formulation can be recommended to manage Acne vulgaris of mild to severe degree as a therapy. PMID- 26865748 TI - Drivers of the composition and diversity of carabid functional traits in UK coniferous plantations. AB - Functional diversity (FD) is increasingly used as a metric to evaluate the impact of forest management strategies on ecosystem functioning. Management interventions that aim to maximise FD require knowledge of multiple environmental drivers of FD, which have not been studied to date in temperate coniferous production forests. We quantified the relative importance of abiotic (forest management) and biotic (ground vegetation community) drivers of carabid FD and trait distribution in 44 coniferous plantation forest stands across the UK. Carabid FD declined with canopy cover and carabid body length correlated negatively with the percentage of open semi-natural area surrounding a plot. We conclude that forest management could enhance carabid FD through initiatives that emulate natural disturbance regimes through gap creation. We found that neither functional nor taxonomic metrics of vegetation diversity correlated with carabid FD, suggesting that restoration of plant communities, a major goal of forest restoration efforts, will not necessarily enhance carabid FD in coniferous plantations. PMID- 26865749 TI - Neonatal mass screening for 21-hydroxylase deficiency. AB - Congenital adrenal hyperplasia(CAH)due to 21-hydroxylase deficiency (21-OHD) is an inherited autosomal recessive disorder. Its incidence is 1 in 10,000 to 20,000 worldwide. This disease shows phenotypic differences, and it is divided into three forms i.e., the salt wasting (SW), simple virilizing (SV), and nonclassic (NC) forms. The most severe form of SW manifests in the first months of life with life-threatening adrenal insufficiency, leading to death. To prevent death by adrenal insufficiency in neonates with the SW form and wrong gender assignment of 46,XX female patients with SW and SV, neonatal mass screening of 21-OHD is performed in several countries including Japan. However, the positive predictive value (PPV) remains low, especially in preterm infants. To reduce the false positive rate and increase the PPV, liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) as a second-tier test may be useful. In this review, the current knowledge on neonatal mass screening of 21-OHD is summarized. PMID- 26865750 TI - Current concepts in perinatal mineral metabolism. AB - The serum levels of calcium (Ca) and phosphate are maintained higher in the fetus than in the pregnant mother, especially in late gestation, to meet the demands of fetal bone development. In order to maintain this fetal stage-specific mineral homeostasis, the placenta plays a critical role through active transcellular mineral transport. Although the molecular mechanism of transplacental Ca transport has been well studied, little is known about the transport mechanism of phosphate and magnesium. Maternal mineral homeostasis is also altered during pregnancy to supply minerals to the fetus. In the lactating mother, osteocytic osteolysis is suggested to be involved in the supply of minerals to the baby. The levels of some calcitropic and phosphotropic (Ca- and phosphate-regulating, respectively) hormones in the fetus are also different from those in the adult. The PTH level in the fetus is lower than that in the mother and nonpregnant adult. It is suggested, however, that low fetal PTH plays an important role in fetal mineral metabolism. The concentration of PTHrP in the fetus is much higher than that of PTH and plays a critical role in perinatal Ca homeostasis. Uncovering the molecular mechanisms for fetal stage-specific mineral metabolism will lead to better management of perinatal patients with mineral abnormalities. PMID- 26865751 TI - A novel mutation of the THRB gene in a Japanese family with resistance to thyroid hormone. PMID- 26865752 TI - Expanding horizons in medical physics: Standardization to visualization and quantitative assessment based personalized treatments. PMID- 26865753 TI - Inter-departmental dosimetry audits - development of methods and lessons learned. AB - External dosimetry audits give confidence in the safe and accurate delivery of radiotherapy. In the United Kingdom, such audits have been performed for almost 30 years. From the start, they included clinically relevant conditions, as well as reference machine output. Recently, national audits have tested new or complex techniques, but these methods are then used in regional audits by a peer-to-peer approach. This local approach builds up the radiotherapy community, facilitates communication, and brings synergy to medical physics. PMID- 26865754 TI - Dosimetric comparison of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, and helical tomotherapy for lung stereotactic body radiotherapy. AB - To compare the treatment plans generated with three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiotherapy (IMRT), and helical tomotherapy (HT) for stereotactic body radiotherapy of lung, twenty patients with medically inoperable (early nonsmall cell lung cancer) were retrospectively reviewed for dosimetric evaluation of treatment delivery techniques (3DCRT, IMRT, and HT). A dose of 6 Gy per fraction in 8 fractions was prescribed to deliver 95% of the prescription dose to 95% volume of planning target volume (PTV). Plan quality was assessed using conformity index (CI) and homogeneity index (HI). Doses to critical organs were assessed. Mean CI with 3DCRT, IMRT, and HT was 1.19 (standard deviation [SD] 0.13), 1.18 (SD 0.11), and 1.08 (SD 0.04), respectively. Mean HI with 3DCRT, IMRT, and HT was 1.14 (SD 0.05), 1.08 (SD 0.02), and 1.07 (SD 0.04), respectively. Mean R50% values for 3DCRT, IMRT, and HT was 8.5 (SD 0.35), 7.04 (SD 0.45), and 5.43 (SD 0.29), respectively. D2cm was found superior with IMRT and HT. Significant sparing of critical organs can be achieved with highly conformal techniques (IMRT and HT) without compromising the PTV conformity and homogeneity. PMID- 26865755 TI - Evaluation of external beam hardening filters on image quality of computed tomography and single photon emission computed tomography/computed tomography. AB - This study was undertaken to evaluate the effect of external metal filters on the image quality of computed tomography (CT) and single photon emission computed tomography (SPECT)/CT images. Images of Jaszack phantom filled with water and containing iodine contrast filled syringes were acquired using CT (120 kV, 2.5 mA) component of SPECT/CT system, ensuring fixation of filter on X-ray collimator. Different thickness of filters of Al and Cu (1 mm, 2 mm, 3 mm, and 4 mm) and filter combinations Cu 1 mm, Cu 2 mm, Cu 3 mm each in combination with Al (1 mm, 2 mm, 3 mm, and 4 mm), respectively, were used. All image sets were visually analyzed for streak artifacts and contrast to noise ratio (CNR) was derived. Similar acquisition was done using Philips CT quality control (QC) phantom and CNR were calculated for its lexan, perspex, and teflon inserts. Attenuation corrected SPECT/CT images of Jaszack phantom filled with 444-555 MBq (12-15 mCi) of (99m)Tc were obtained by applying attenuation correction map generated by hardened X-ray beam for different filter combination, on SPECT data. Uniformity, root mean square (rms) and contrast were calculated in all image sets. Less streak artifacts at iodine water interface were observed in images acquired using external filters as compared to those without a filter. CNR for syringes, spheres, and inserts of Philips CT QC phantom was almost similar to Al 2 mm, Al 3 mm, and without the use of filters. CNR decreased with increasing copper thickness and other filter combinations. Uniformity and rms were lower, and value of contrast was higher for SPECT/CT images when CT was acquired with Al 2 mm and 3 mm filter than for images acquired without a filter. The study suggests that for Infinia Hawkeye 4, SPECT/CT system, Al 2 mm, and 3 mm are the optimum filters for improving image quality of SPECT/CT images of Jaszack or Philips CT QC phantom keeping other parameters of CT constant. PMID- 26865756 TI - The dosimetric impact of different photon beam energy on RapidArc radiotherapy planning for cervix carcinoma. AB - The main purpose of this study is to know the effect of three different photon energies viz., 6, 10, and 15 mega voltage (MV) on RapidArc (RA) planning for deep seated cervix tumor and to develop clinically acceptable RA plans with suitable photon energy. RA plans were generated for 6, 10, and 15 MV photon energies for twenty patients reported with cervix carcinoma. RA plans were evaluated in terms of planning target volume (PTV) coverage, dose to organs at risk (OARs), conformity index (CI), homogeneity index (HI), gradient measure, external volume index of dose distribution produced, total number of monitor units (MUs), nontumor integral dose (ID), and low dose volume of normal tissue. A two-sample paired t-test was performed to compare the dosimetric parameters of RA plans. Irrespective of photon energy used for RA planning, plans were dosimetrically similar in terms of PTV coverage, OARs sparing, CI and HI. The numbers of MUs were 13.4 +/- 1.4% and 18.2 +/- 1.5% higher and IDs were 2.7 +/- 0.8% and 3.7 +/- 0.9% higher in 6 MV plans in comparison to that in the 10 and 15 MV plans, respectively. V1Gy, V2Gy, V3Gy, and V4Gy were higher in 6 MV plans in comparison to that in 10 and 15 MV plans. Based on this study, 6 MV photon beam is a good choice for RA planning in case of cervix carcinoma, as it does not deliver additional exposure to patients caused by photoneutrons produced in high energy beams. PMID- 26865757 TI - Dose and linear energy transfer distributions of primary and secondary particles in carbon ion radiation therapy: A Monte Carlo simulation study in water. AB - The factors influencing carbon ion therapy can be predicted from accurate knowledge about the production of secondary particles from the interaction of carbon ions in water/tissue-like materials, and subsequently the interaction of the secondary particles in the same materials. The secondary particles may have linear energy transfer (LET) values that potentially increase the relative biological effectiveness of the beam. Our primary objective in this study was to classify and quantify the secondary particles produced, their dose averaged LETs, and their dose contributions in the absorbing material. A 1 mm diameter carbon ion pencil beam with energies per nucleon of 155, 262, and 369 MeV was used in a geometry and tracking 4 Monte Carlo simulation to interact in a 27 L water phantom containing 3000 rectangular detector voxels. The dose-averaged LET and the dose contributions of primary and secondary particles were calculated from the simulation. The results of the simulations show that the secondary particles that contributed a major dose component had LETs <100 keV/um. The secondary particles with LETs >600 keV/um contributed only <0.3% of the dose. PMID- 26865758 TI - Use of image guided radiation therapy techniques and imaging dose measurement at Indian hospitals: A survey. AB - A national survey was conducted to obtain information about the use of image guided radiotherapy (IGRT) techniques and IGRT dose measurement methods being followed at Indian radiotherapy centers. A questionnaire containing parameters relevant to use of IGRT was prepared to collect the information pertaining to (i) availability and type of IGRT delivery system, (ii) frequency of image acquisition protocol and utilization of these images for different purpose, and (iii) imaging dose measurement. The questionnaire was circulated to 75 hospitals in the country having IGRT facility, and responses of 51 centers were received. Survey results showed that among surveyed hospitals, 86% centers have IGRT facility, 78% centers have kilo voltage three-dimensional volumetric imaging. 75% of hospitals in our study do not perform computed tomography dose index measurements and 89% of centers do not perform patient dose measurements. Moreover, only 29% physicists believe IGRT dose is additional radiation burden to patient. This study has brought into focus the need to design a national protocol for IGRT dose measurement and development of indigenous tools to perform IGRT dose measurements. PMID- 26865759 TI - Impact of dose rate on accuracy of intensity modulated radiation therapy plan delivery using the pretreatment portal dosimetry quality assurance and setting up the workflow at hospital levels. AB - The aim of this study was to examine the impact of dose rate on accuracy of intensity modulated radiation therapy (IMRT) plan delivery by comparing the gamma agreement between the calculated and measured portal doses by pretreatment quality assurance (QA) using electronic portal imaging device dosimetry and creating a workflow for the pretreatment IMRT QA at hospital levels. As the improvement in gamma agreement leads to increase in the quality of IMRT treatment delivery, gamma evaluation was carried out for the calculated and the measured portal images for the criteria of 3% dose difference and 3 mm distance-to agreement (DTA). Three gamma parameters: Maximum gamma, average gamma, and percentage of the field area with a gamma value>1.0 were analyzed. Three gamma index parameters were evaluated for 40 IMRT plans (315 IMRT fields) which were calculated for 400 monitor units (MU)/min dose rate and maximum multileaf collimator (MLC) speed of 2.5 cm/s. Gamma parameters for all 315 fields are within acceptable limits set at our center. Further, to improve the gamma results, we set an action level for this study using the mean and standard deviation (SD) values from the 315 fields studied. Forty out of 315 IMRT fields showed low gamma agreement (gamma parameters>2 SD as per action level of the study). The parameters were recalculated and reanalyzed for the dose rates of 300, 400 and 500 MU/min. Lowering the dose rate helped in getting an enhanced gamma agreement between the calculated and measured portal doses of complicated fields. This may be attributed to the less complex motion of MLC over time and the MU of the field/segment. An IMRT QA work flow was prepared which will help in improving the quality of IMRT delivery. PMID- 26865760 TI - Setup error analysis in helical tomotherapy based image-guided radiation therapy treatments. AB - The adequacy of setup margins for various sites in patients treated with helical tomotherapy was investigated. A total of 102 patients were investigated. The breakdown of the patients were as follows: Twenty-five patients each in brain, head and neck (H and N), and pelvis, while 12 patients in lung and 15 in craniospinal irradiation (CSI). Patients were immobilized on the institutional protocol. Altogether 2686 megavoltage computed tomography images were analyzed with 672, 747, 622, 333, and 312 fractions, respectively, from brain, H and N, pelvis, lung, and CSI. Overall systematic and random errors were calculated in three translational and three rotational directions. Setup margins were evaluated using van Herk formula. The calculated margins were compared with the margins in the clinical use for various directions and sites. We found that the clinical isotropic margin of 3 mm was adequate for brain patients. However, in the longitudinal direction it was found to be out of margin by 0.7 mm. In H and N, the calculated margins were well within the isotropic margin of 5 mm which is in clinical use. In pelvis, the calculated margin was within the limits, 8.3 mm versus 10 mm only in longitudinal direction, however, in vertical and lateral directions the calculated margins were out of clinical margins 11 mm versus 10 mm, and 8.7 mm versus 7.0, mm respectively. In lung, all the calculated margins were well within the margins used clinically. In CSI, the variation was found in the middle spine in the longitudinal direction. The clinical margins used in our hospital are adequate enough for sites H and N, lung, and brain, however, for CSI and pelvis the margins were found to be out of clinical margins. PMID- 26865762 TI - In response to Swamidas and Kirisits. PMID- 26865761 TI - Derivative based sensitivity analysis of gamma index. AB - Originally developed as a tool for patient-specific quality assurance in advanced treatment delivery methods to compare between measured and calculated dose distributions, the gamma index (gamma) concept was later extended to compare between any two dose distributions. It takes into effect both the dose difference (DD) and distance-to-agreement (DTA) measurements in the comparison. Its strength lies in its capability to give a quantitative value for the analysis, unlike other methods. For every point on the reference curve, if there is at least one point in the evaluated curve that satisfies the pass criteria (e.g., deltaDD = 1%, deltaDTA = 1 mm), the point is included in the quantitative score as "pass." Gamma analysis does not account for the gradient of the evaluated curve - it looks at only the minimum gamma value, and if it is <1, then the point passes, no matter what the gradient of evaluated curve is. In this work, an attempt has been made to present a derivative-based method for the identification of dose gradient. A mathematically derived reference profile (RP) representing the penumbral region of 6 MV 10 cm * 10 cm field was generated from an error function. A general test profile (GTP) was created from this RP by introducing 1 mm distance error and 1% dose error at each point. This was considered as the first of the two evaluated curves. By its nature, this curve is a smooth curve and would satisfy the pass criteria for all points in it. The second evaluated profile was generated as a sawtooth test profile (STTP) which again would satisfy the pass criteria for every point on the RP. However, being a sawtooth curve, it is not a smooth one and would be obviously poor when compared with the smooth profile. Considering the smooth GTP as an acceptable profile when it passed the gamma pass criteria (1% DD and 1 mm DTA) against the RP, the first and second order derivatives of the DDs (deltaD', deltaD") between these two curves were derived and used as the boundary values for evaluating the STTP against the RP. Even though the STTP passed the simple gamma pass criteria, it was found failing at many locations when the derivatives were used as the boundary values. The proposed derivative-based method can identify a noisy curve and can prove to be a useful tool for improving the sensitivity of the gamma index. PMID- 26865763 TI - Reply to the comment of S. VanDyk and K. Narayan on the editorial "IMRT, IGRT and other high technology become standard in external beam radiotherapy: But is image guided brachytherapy for cervical cancer too expensive?" J Med Phys 2015;40:1-4. PMID- 26865764 TI - Dynamic and static asana practices. PMID- 26865765 TI - Understanding Vrikshasana using body mounted sensors: A statistical approach. AB - AIM: A scheme for understanding how the human body organizes postural movements while performing Vrikshasana is developed in the format of this paper. SETTINGS AND DESIGN: The structural characteristics of the body and the geometry of the muscular actions are incorporated into a graphical representation of the human movement mechanics in the frontal plane. A series of neural organizational hypotheses enables us to understand the mechanics behind the hip and ankle strategy: (1) Body sway in the mediolateral direction; and (2) influence of hip and ankle to correct instabilities caused in body while performing Vrikshasana. MATERIALS AND METHODS: A methodological study on 10 participants was performed by mounting four inertial measurement units on the surface of the trapezius, thoracolumbar fascia, vastus lateralis, and gastrocnemius muscles. The kinematic accelerations of three mutually exclusive trials were recorded for a period of 30 s. RESULTS: The results of every trial were processed using two different approaches namely statistical signal processing (variance and cross-correlation). Conclusions obtained from both these studies were in favor of the initial hypothesis. CONCLUSIONS: This study enabled us to understand the role of hip abductors and adductors, and ankle extensions and flexions in correcting the posture while performing Vrikshasana. PMID- 26865766 TI - Effect of uninostril yoga breathing on brain hemodynamics: A functional near infrared spectroscopy study. AB - OBJECTIVES: To measure the effect of the right and left nostril yoga breathing on frontal hemodynamic responses in 32 right handed healthy male subjects within the age range of 18-35 years (23.75 +/- 4.14 years). MATERIALS AND METHODS: Each subject practiced right nostril yoga breathing (RNYB), left nostril yoga breathing (LNYB) or breath awareness (BA) (as control) for 10 min at the same time of the day for three consecutive days, respectively. The sequence of intervention was assigned randomly. The frontal hemodynamic response in terms of changes in the oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), and total hemoglobin (totalHb or blood volume) concentration was tapped for 5 min before (pre) and 10 min during the breathing practices using a 16 channel functional near-infrared system (FNIR100-ACK-W, BIOPAC Systems, Inc., U.S.A.). Average of the eight channels on each side (right and left frontals) was obtained for the two sessions (pre and during). Data was analyzed using SPSS version 10.0 through paired and independent samples t-test. RESULTS: Within group comparison showed that during RNYB, oxyHb levels increased significantly in the left prefrontal cortex (PFC) as compared to the baseline (P = 0.026). LNYB showed a trend towards significance for reduction in oxyHb in the right hemisphere (P = 0.057). Whereas BA caused significant reduction in deoxyHb (P = 0.023) in the left hemisphere. Between groups comparison revealed that oxyHb and blood volume in the left PFC increased significantly during RNYB as compared to BA (oxyHb: P =0.012; TotalHb: P =0.017) and LNYB (oxyHb: P =0.024; totalHb: P =0.034). CONCLUSION: RNYB increased oxygenation and blood volume in the left PFC as compared to BA and LNYB. This supports the relationship between nasal cycle and ultradian rhythm of cerebral dominance and suggests a possible application of uninostril yoga breathing in the management of psychopathological states which show lateralized cerebral dysfunctions. PMID- 26865767 TI - Improvements in well-being and vagal tone following a yogic breathing-based life skills workshop in young adults: Two open-trial pilot studies. AB - BACKGROUND: While efficacy of Sudarshan Kriya Yoga (SKY) has been demonstrated in a number of prior studies, little is known about the effects of SKY taught as part of the Your Enlightened Side (YES+) workshop designed for college students and other young adults. AIMS: This study aimed to assess the effects of YES+, a yogic breathing-based life skills workshop, on multiple measures of well-being and physiological stress response. MATERIALS AND METHODS: Two nonrandomized open trial pilot studies were conducted with a total of 74 young adults (age 25.4 +/- 6.6 years; 55% female). Study 1 collected a variety of self-report questionnaires at baseline, postworkshop, and 1-month follow-up. Study 2 collected self-report questionnaires in addition to electrocardiography with a stationary cycling challenge at baseline and 1-month follow-up. RESULTS: Study 1: Improvements in self-reported depression (P's <= 0.010), perceived stress (P's <= 0.002), life satisfaction (P's <= 0.002), social connectedness (P's <= 0.004), and gratitude (P's <= 0.090) were observed at postworkshop and 1-month after workshop relative to baseline. Study 2: Improvements in self-reported emotion regulation were observed at 1-month follow-up relative to baseline (P = 0.019). Positive and Negative Affect Schedule-Expanded Form positive affect increased (P = 0.021), while fatigue and sadness decreased (P's <= 0.005). During the stationary cycling challenge, rate to recovery of electrocardiography inter-beat interval also increased from baseline to 1-month follow-up (P = 0.077). CONCLUSIONS: These findings suggest that a life skills workshop integrating yogic breathing techniques may provide self-empowering tools for enhancing well-being in young adults. Future research is indicated to further explore these effects, particularly in regards to vagal tone and other aspects of stress physiology. PMID- 26865768 TI - Impact of 10-weeks of yoga practice on flexibility and balance of college athletes. AB - BACKGROUND: With clearer evidence of its benefits, coaches, and athletes may better see that yoga has a role in optimizing performance. AIMS: To determine the impact of yoga on male college athletes (N = 26). METHODS: Over a 10-week period, a yoga group (YG) of athletes (n = 14) took part in biweekly yoga sessions; while a nonyoga group (NYG) of athletes (n = 12) took part in no additional yoga activity. Performance measures were obtained immediately before and after this period. Measurements of flexibility and balance, included: Sit-reach (SR), shoulder flexibility (SF), and stork stand (SS); dynamic measurements consisted of joint angles (JA) measured during the performance of three distinct yoga positions (downward dog [DD]; right foot lunge [RFL]; chair [C]). RESULTS: Significant gains were observed in the YG for flexibility (SR, P = 0.01; SF, P = 0.03), and balance (SS, P = 0.05). No significant differences were observed in the NYG for flexibility and balance. Significantly, greater JA were observed in the YG for: RFL (dorsiflexion, l-ankle; P = 0.04), DD (extension, r-knee, P = 0.04; r-hip; P = 0.01; flexion, r-shoulder; P = 0.01) and C (flexion, r-knee; P = 0.01). Significant JA differences were observed in the NYG for: DD (flexion, r knee, P = 0.01: r-hip, P = 0.05; r-shoulder, P = 0.03) and C (flexion r-knee, P = 0.01; extension, r-shoulder; P = 0.05). A between group comparison revealed the significant differences for: RFL (l-ankle; P = 0.01), DD (r-knee, P = 0.01; r hip; P = 0.01), and C (r-shoulder, P = 0.02). CONCLUSIONS: Results suggest that a regular yoga practice may increase the flexibility and balance as well as whole body measures of male college athletes and therefore, may enhance athletic performances that require these characteristics. PMID- 26865769 TI - Effect of integrated Yoga module on positive and negative emotions in Home Guards in Bengaluru: A wait list randomized control trial. AB - BACKGROUND: The beneficial aspect of positive emotions on the process of learning and the harmful affect of negative emotions on coping with stress and health are well-documented through studies. The Home Guards (HGs) are working in a very stressful situation during election, managing traffic and other crowded places. It is quite essential in present day circumstances that they have to manage their emotions and cope up with different stressful situations. OBJECTIVE: To study the efficacy of integrated Yoga module (IYM) on emotions (positive and negative affect [PA and NA]) of HGs. METHODS: A total of 148 HGs both males and females who qualified the inclusion and exclusion criteria were randomly divided into Yoga group (YG) and control groups (CG). The YG had supervised practice sessions (by trained experts) for 1 h daily, 6 days a week for 8 weeks along with their regular routine work whereas CG performing their routine work. Positive affect negative affect scale (PANAS) was assessed before and after 8 weeks using a modified version of PANAS. RESULTS: PA in YG had significantly increased (P < 0.05) whereas it had decreased significantly (P < 0.05) in CG. Other positive effect in YG had significantly increased (P < 0.001), whereas it had decreased significantly (P < 0.001) in CG. NA in YG had significantly decreased (P < 0.001), whereas it had significantly increased (P < 0.001) in CG. Other NA in YG had significantly decreased (P < 0.001), whereas it had significantly increased (P < 0.01) in CG. CONCLUSIONS: The results suggested that IYM can be useful for HGs to improve the PA and to decrease NA score. Moreover, IYM is cost-effective and helps HGs for coping up with emotions in stressful situations. PMID- 26865770 TI - Effects of Yogasanas on osteoporosis in postmenopausal women. AB - BACKGROUND: Osteoporosis is commonly encountered by postmenopausal women. There is an increased need for a low cost and efficient treatment alternative to address this population. AIMS: To study the effects of integrated yoga on bone mineral density (BMD) in postmenopausal women with osteoporosis. SETTINGS AND DESIGNS: Experimental pre-post study conducted in a community setting. MATERIALS AND METHODS: 30 females in the age group of 45-62 years suffering from postmenopausal osteoporosis with a dual-energy X-ray absorptiometry (DEXA) score of <=-2.5 underwent a 6 months fully supervised yoga session. All the participants completed the study. Pretraining and posttraining BMD was calculated. OUTCOME MEASURE: DEXA score at the lumbar spine. STATISTICAL ANALYSIS: The study was statistically analyzed using paired t-test to see the significance of pretraining and posttraining effects of a yoga session. RESULTS: Improvement in T-score of DEXA scan of -2.55 +/- 0.25 at posttraining as compared to a pretraining score of -2.69 +/- 0.17. CONCLUSIONS: Integrated yoga is a safe mode of physical activity which includes weight bearing as well as not weight bearing asanas, Pranayama, and suryanamaskar, all of which helps induce improvement in BMD in postmenopausal osteoporotic females. PMID- 26865771 TI - Development of normative data of electro photonic imaging technique for healthy population in India: A normative study. AB - BACKGROUND: Electro photonic imaging (EPI) technique is growing as a novel technique of health assessment and is being utilized in the fields of alternative medicine, conventional practices, psycho-physiology, psychology, and consciousness studies. The existing EPI norms are based mostly on European (EU) population. In order to enhance the practice and research through EPI in India, there is a need for developing norms for the healthy Indian population. OBJECTIVE: The objective of the study was to establish the normative data of EPI for the healthy Indian population, to aid in the accuracy of EPI measurements and interpretations. MATERIALS AND METHODS: A total of 1297 volunteers were assessed once, who represented different parts of India during December 2013 to December 2014. Among them, 880 volunteers were reported to be healthy (age mean +/- standard deviation [SD], 33.55 +/- 10.92), with 584 males (age mean +/- SD, 33.54 +/- 10.86) and 296 females (age mean +/- SD, 33.56 +/- 11.00). In this study activation coefficient (stress level), integral area (IA) (general health), and integral entropy (disorderliness in energy) parameters were analyzed. RESULTS: As the data were not normally distributed, quartile based statistics was used for setting the norms. The 25(th) and 75(th) percentiles were calculated and they were further verified using a bootstrap procedure. Uniquely, the results showed a clear difference in IA parameters under both with filter (physiological) and without filter (psycho-physiological) conditions between the Indian and the EU population. Though other parameters were found almost similar to the EU population, inter quartile ranges were narrower in the Indian population as compared to the EU values. Similar trends were observed in the subgroup analyzes: That is, male versus female genders and age ranges 18-40 versus 40-60. CONCLUSION: As compared to EU population, Indian population had different range of Integral Area values and narrower range for values of other variables. EPI Studies in India should also adjust for factors such as age and gender. PMID- 26865772 TI - Effect of Integrated Yoga (IY) on psychological states and CD4 counts of HIV-1 infected patients: A randomized controlled pilot study. AB - BACKGROUND: Human immunodeficiency virus (HIV) infected individuals frequently suffer from anxiety and depression. Depression has been associated with rapid decline in CD4 counts and worsened treatment outcomes in HIV-infected patients. Yoga has been used to reduce psychopathology and improve immunity. AIM: To study the effect of 1-month integrated yoga (IY) intervention on anxiety, depression, and CD4 counts in patients suffering from HIV-1 infection. METHODS: Forty four HIV-1 infected individuals from two HIV rehabilitation centers of Manipur State of India were randomized into two groups: Yoga (n = 22; 12 males) and control (n = 22; 14 males). Yoga group received IY intervention, which included physical postures (asanas), breathing practices (pranayama), relaxation techniques, and meditation. IY sessions were given 60 min/day, 6 days a week for 1 month. Control group followed daily routine during this period. All patients were on anti retroviral therapy (ART) and dosages were kept stable during the study. There was no significant difference in age, gender, education, CD4 counts, and ART status between the two groups. Hospital anxiety and depression scale was used to assess anxiety and depression, CD4 counts were measured by flow cytometry before and after intervention. Analysis of variance - repeated measures was applied to analyze the data using SPSS version 10. RESULTS: Within group comparison showed a significant reduction in depression scores (F [1, 21] =4.19, P < 0.05) and non significant reduction in anxiety scores along with non significant increment in CD4 counts in the yoga group. In the control group, there was a non-significant increase in anxiety and depression scores and reduction in CD4 counts. Between group comparison revealed a significant reduction in depression scores (F [1, 21] =5.64, P < 0.05) and significant increase in CD4 counts (F [1, 21] =5.35, P < 0.05) in the yoga group as compared to the control. CONCLUSION: One month practice of IY may reduce depression and improve immunity in HIV-1 infected adults. PMID- 26865773 TI - Impact of short-term practice of yoga on heart rate variability. AB - BACKGROUND: Yoga is a science that facilitates homeostasis, an ancient way of life intended to improve the quality of life of an individual. Practice of yoga is proposed to alter the autonomic nervous system and affect the cardiovascular functioning. This study was intended to assess the influence of short-term practice of yoga for a month on heart rate variability (HRV). MATERIALS AND METHODS: Totally, 40 healthy male volunteers in the age group of 30-60 years willing to practice yoga for a month were included in the study. HRV was assessed using HRV device (RMS Vagus, India). Preinterventional assessment of HRV was done in these subjects. Practice of yoga that included a set of physical postures (asanas), breathing techniques (pranayama), and meditation (dhyana) were performed for an hour daily for 1 month under the guidance of a certified yoga instructor. Postinterventional assessment of HRV was done. The values were expressed in median and their interquartile range, and statistical analysis was done to compare the changes using Wilcoxon Signed Rank Test. RESULTS: Thirty-two of 40 subjects recruited for yoga practice completed the study protocol. Analysis of HRV revealed that in time domain parameters, SDNN increased from 33.60 (31.41 44.82) to 42.11 (34.43-57.51), RMSSD increased from 22.00 (16.00-33.80) to 25.6 (17.0-34.8), and PNN50 increased from 2.45 (0.80-15.38) to 7.35 (1.40-18.57) after intervention. In the frequency domain parameters, the low-frequency (LF) power spectrum reduced from 39.30 (25.1-46.25) to 30.40 (22.75-40.62) and LF/high frequency ratio was reduced from 2.62 (1.91-4.07) to 2.28 (1.4-3.07) after 1 month practice of yoga. P < 0.05 was considered statistically significant. CONCLUSION: Autonomic balance tilts toward parasympathetic predominance after 1 month practice of yoga. PMID- 26865774 TI - Yoga and mental health: A dialogue between ancient wisdom and modern psychology. AB - BACKGROUND: Many yoga texts make reference to the importance of mental health and the use of specific techniques in the treatment of mental disorders. Different concepts utilized in modern psychology may not come with contemporary ideas, instead, they seem to share a common root with ancient wisdom. AIMS: The goal of this perspective article is to correlate modern techniques used in psychology and psychiatry with yogic practices, in the treatment of mental disorders. MATERIALS AND METHODS: The current article presented a dialogue between the yogic approach for the treatment of mental disorder and concepts used in modern psychology, such as meta-cognition, disidentification, deconditioning and interoceptive exposure. CONCLUSIONS: Contemplative research found out that modern interventions in psychology might not come from modern concepts after all, but share great similarity with ancient yogic knowledge, giving us the opportunity to integrate the psychological wisdom of both East and West. PMID- 26865775 TI - Effect of Sudarshan Kriya (meditation) on gamma, alpha, and theta rhythm during working memory task. AB - AIMS: The present study focuses on analyzing the effects of Sudarshan Kriya yoga (SKY) on brain signals during a working memory (WM) task. To envision the significant effects of SKY on WM capacity (WMC), we chose a control group for contriving a cogent comparison that could be corroborated using statistical tests. SUBJECTS AND METHODS: A total of 25 subjects were taken in the study, of which 10 were allotted to a control group and 15 to an experimental group. Electroencephalograph was taken during a WM task, which was an automated operation span test before and after SKY with 90 days intervals. No SKY was given to the control group. STATISTICAL ANALYSIS USED: t-test and one-way ANOVA were applied. RESULTS: SKY promoted the efficient use of energy and power spectral density (PSD) for different brain rhythms in the desired locations as depicted by the gamma (F8 channel), alpha, and theta 2 (F7 and FC5) bands. It was found that gamma PSD reduced for both phases of memory in the experimental group. Alpha energy increased during the retrieval phase in the experimental group after SKY. Theta 1 rhythm was not affected by SKY, but theta 2 had shown left hemispheric activation. Theta rhythm was associated with memory consolidation. CONCLUSIONS: SKY had shown minimized energy losses while performing the task. SKY can improve WMC by changing the brain rhythms such that energy is utilized efficiently in performing the task. PMID- 26865776 TI - Examining the energy cost and intensity level of prenatal yoga. AB - CONTEXT: A popular form of pregnancy physical activity (PA) is prenatal yoga. However, little is known about the intensity and energy cost of this practice. AIMS: To examine the energy cost and intensity level of prenatal yoga. METHODS: Pregnant women in a prenatal yoga class (n = 19) wore a Sense Wear Armband during eleven 60 min classes each, and self-reported demographic variables, height and weight, prepregnancy weight, and PA behaviors and beliefs. Sense Wear Armband data included kilocalories, metabolic equivalent (MET) values, and time spent in various intensities. Descriptive statistics and frequencies were utilized to describe energy expenditure and intensity. RESULTS: Energy expenditure averaged 109 +/- 8 kcals, and the average MET value was 1.5 +/- 0.02. On average, 93% and 7% of classes were sedentary and moderate intensity PA, respectively. CONCLUSIONS: Time spent in a prenatal yoga class was considered to be primarily a sedentary activity. Future research should utilize larger samples, practice type, and skill level to increase generalizability. PMID- 26865777 TI - Effects of multisensory yoga on behavior in a male child with Apert and Asperger syndrome. AB - This case focused on a 7-year-old boy with Apert and Asperger's syndrome who attended 8, 45 min multisensory yoga sessions, twice a week, during 4-week camp. Results from the pre- and post-tests on Treatment and Research Institute for Autism Social Skills Assessment showed improvements in the total score changes from 19 to 7 for disruptive behaviors. Sparks Target Behavior Checklist scores changed from eight to one showing progression in ability to stay on task. Yoga Pose Rating Scale displayed the transformation in total scores from 80 = emerging to 115 = consistency in pose performance. The field notes revealed the positive development in expressive emotions, social engagement, and decline in looking around. Outside class parent and school behavioral specialist reported the improved ability to self-regulate stress using lion's breath and super brain. These findings indicate an improvement in behaviors that influenced the physical performance, emotional expression, and social interaction after yoga training for this child. PMID- 26865778 TI - Yoga in 42 African American women's memoirs reveal hidden tradition of health. PMID- 26865779 TI - University-based online yoga education: A pilot study of students' experience. PMID- 26865781 TI - Witnessing consciousness. PMID- 26865780 TI - Unsubstantiated conclusions from improper statistical design and analysis of a randomized controlled trial. PMID- 26865782 TI - Complications in Cosmetic Surgery: A Time to Reflect and Review and not Sweep Them Under the Carpet. PMID- 26865783 TI - Complications Associated With Medial Thigh Lift: A Comprehensive Literature Review. AB - Medial contouring of the thigh is frequently requested to improve appearance and function of medial thigh deformities, following massive weight loss or aging process. This surgical procedure can be associated with a significant rate of complications. Our aim was to consider the complications and outcomes according to the performed technique, through a wide and comprehensive review of the literature. A search on PubMed/Medline was performed using "medial thighplasty", "medial thigh lifting" and "technique" as key words. As inclusion criteria, we selected the clinical studies describing techniques of medial thighplasty. We excluded the papers in which complications related to medial thighplasty were not specified. We also excluded literature-review articles. We found 16 studies from 1988 to 2015. Overall, 447 patients were treated. Different techniques were applied. Complications were observed in 191/447 patients (42.72%). The most frequent complications were wound dehiscence(18.34%) and seroma (8.05%). No major complications, such as thromboembolism and sepsis, were observed. Minor complications occurred in a high percent of patients, regardless of the performed surgical procedure. Patients should be informed about the possible occurrence of wound dehiscence and seroma, as common complications associated with this surgical procedure. PMID- 26865785 TI - A Study of Hair Follicular Transplantation as a Treatment Option for Vitiligo. AB - BACKGROUND: Repigmentation of vitiligo is closely related to hair follicles. Hence, replenishing melanocytes in vitiliginous patches utilizing undifferentiated stem cells of the hair follicles using follicular unit transplantation (FUT) is a possible treatment option. OBJECTIVES OF THE STUDY: To study the efficacy of FUT in cases of segmental/stabilized vitiligo as a treatment option for leukotrichia. MATERIALS AND METHODS: Fifty patients with 63 lesions of stable vitiligo over nonglabrous areas were treated with follicular unit grafts. Reduction in the size of vitiligo patches as well as improvement in the associated leukotrichia were evaluated using subjective and objective assessments. RESULTS: Of the 63 patches, good to excellent response was seen in 39 (61.9%), fair in 16 (25.4%), and poor in eight (12.7%) lesions. No repigmentation was seen in two (4.8%) lesions. The mean improvement seen was 61.17%. Excellent color match was observed in 44 lesions (69.8%). Repigmentation of the depigmented hairs occurred in 11 out of 46 patients with associated leukotrichia. CONCLUSION: FUT is a safe and effective method for treating localized and segmental vitiligo, especially on hairy parts of the skin. Though labor intensive, it was found to be associated with a quick patient recovery time, very low morbidity, and good color match. PMID- 26865784 TI - Managing Complications of Fillers: Rare and Not-So-Rare. AB - Fillers belong to the most frequently used beautifying products. They are generally well tolerated, but any one of them may occasionally produce adverse side effects. Adverse effects usually last as long as the filler is in the skin, which means that short-lived fillers have short-term side effects and permanent fillers may induce life-long adverse effects. The main goal is to prevent them, however, this is not always possible. Utmost care has to be given to the prevention of infections and the injection technique has to be perfect. Treatment of adverse effects is often with hyaluronidase or steroid injections and in some cases together with 5-fluorouracil plus allopurinol orally. Histological examination of biopsy specimens often helps to identify the responsible filler allowing a specific treatment to be adapted. PMID- 26865786 TI - Aesthetic reconstruction of the upper antihelix in external ear with banner pull through flap. AB - INTRODUCTION: We can use pre auricular and post auricular skin as a pull through flap for upper antihelix defects reconstruction. PATIENTS AND METHODS: This was a prospective case-series study, which was done in the Department of Plastic and Reconstructive Surgery Ward. In this study, 15 patients (3 women, 12 men), ranging from 45 to 72 years old (mean, 58 years) underwent operation with pull through banner flap for reconstruction of upper antihelix (7 cases) and triangular fossa with superior and inferior crura (5cases) caused by BCC or SCC excision. Reconstruction of upper antihelix defects up to 20 * 30 mm with post auricle pull through flap and reconstruction of triangular fossa up to 20 * 20 mm with pre auricle pull through flap were done. RESULTS: Our study showed that pull through flap with superior pedicle from post auricular and preauricular area was an effective method for reconstruction of upper ear antihelix defects. CONCLUSION: We advocate that the pull through flap with superior pedicle from post auricle and pre auricle is an excellent choice for reconstruction of upper antihelix ear reconstruction in both crura and triangular fossa. PMID- 26865787 TI - Treatment of Postinflammatory Pigmentation Due to Acne with Q-Switched Neodymium Doped Yttrium Aluminum Garnet In 78 Indian Cases. AB - BACKGROUND: Postinflammatory hyperpigmentation (PIH) is a common sequela seen in the Indian population following affliction by acne. It is psychologically extremely disturbing for the patients and can severely affect the quality of life. Very few therapeutic modalities have proved to be really efficacious in this condition. AIMS: The aim was to review our experience with 1,064-nm Q switched neodymium-doped yttrium aluminum garnet (QSNY) laser in the treatment of PIH. MATERIALS AND METHODS: Seventy-eight patients with postacne hyperpigmentation were included in the study. They were treated with six sessions at two weekly intervals using a 1,064-nm QSNY laser. Patient and physician scores were assessed at 1 month and 3 months after the last treatment. Clinical photographs also were reviewed to determine the efficacy. Adverse effects were noted. RESULTS: Seventy percent of the patients reported significant improvement in hyperpigmentation as compared to the baseline. The majority of the adverse events were limited to mild, brief erythema. CONCLUSION: The 1,064-nm QSNY laser is an effective modality for the treatment of PIH caused by acne. PMID- 26865788 TI - Novel treatment of Hori's nevus: A combination of fractional nonablative 2,940-nm Er:YAG and low-fluence 1,064-nm Q-switched Nd:YAG laser. AB - OBJECTIVE: To demonstrate a combination laser therapy to treat Hori's nevus. DESIGN: A prospective study. SETTING: A Singapore-based clinic. PARTICIPANTS: Five female patients, aged 30-46 years, with bilateral malar Hori's nevus. MEASUREMENTS: Photographs were taken before treatment and 1 month after laser treatment was completed. These were graded by three independent physicians. The patients were also asked to grade their treatment response subjectively. They were followed up for a total of 3 months after laser treatment to monitor recurrence. MATERIALS AND METHODS: The fractional nonablative 2,940-nm Er:YAG laser with a fluence of 0.7 J/cm(2), spot size 12 mm, and frequency 15 Hz was used to perform a full-face single-pass treatment. Subsequently, a second pass and third pass over Hori's nevi were done bilaterally till the clinical endpoint of skin whitening. The 1,064-nm Q-switched (QS) Nd:YAG at a fluence of 2.0 J/cm(2), frequency 2 Hz, and 4-mm spot size was used to deliver multiple passes over Hori's nevus till erythema with mild petechiae appeared. We repeated the treatment once a week for 3 more consecutive weeks. RESULTS: All five patients had above 80% improvement in their pigmentation and two (skin type III) achieved complete 100% clearance. Based on the patients' subjective assessments, all five of them expressed satisfaction and felt that their pigmentation had improved. There were no complications noted. CONCLUSION: The fractional nonablative 2940 nm Er:YAG laser and Q-switched 1064nm laser Nd:YAG combination is an effective and safe treatment for Hori's nevus. PMID- 26865789 TI - Novel Low Fluence Combination Laser Treatment of Solar Lentigines in Type III Asian Skin. AB - OBJECTIVE: To demonstrate a novel low fluence combination laser technique [Erbium doped yttrium aluminum garnet (Erb:YAG) and neodymium-doped yttrium aluminum garnet (Nd:YAG)] to effectively treat solar lentigines in type III Asian skin in a single session. DESIGN: A prospective study. SETTING: A Singapore-based clinic. PARTICIPANTS: Five patients (all females) were enrolled into the study. The ages ranged 35-60 years; all patients had Fitzpatrick skin type III. MEASUREMENTS: Photographs were taken at baseline and at 1-month follow-up. These were reviewed by two independent physicians who were blinded to the study. Changes in pigment severity were assessed by a 5-point scale (1: Aggravation of pigment, 2: No change, 3: 25-50% improvement, 4: 51-75% improvement, and 5: 76-100% improvement). RESULTS: All patients received a single treatment session. At 1 month follow-up, a reduction in pigment was observed in all patients. Both physicians' reports were independently agreeable. All patients scored 5, having >90% improvement in pigment severity. No hypopigmentation, postinflammatory hyperpigmentation (PIH), or recurrence was seen. CONCLUSION: Low fluence combination laser is effective and safe for clearance of solar lentigines in type III Asian skin. PMID- 26865790 TI - Lasers for Lentigines, from Q-Switched to Erbium-Doped Yttrium Aluminium Garnet Micropeel, is There a Need to Reinvent the Wheel? PMID- 26865791 TI - Why Do Females Use Botulinum Toxin Injections? AB - BACKGROUND: Botulinum toxin (BT) use for enhancing the facial features has become a commonly accepted form of aesthetic intervention. This study conducted a self report survey of female BT users in order to explore the motivating factors in its use (cost-benefit analysis). SETTINGS AND DESIGN: This is a cross-sectional exploratory pilot study. MATERIALS AND METHODS: Self-report questionnaires were administered to 41 consecutive clients attending an independent medical practice for BT injections for cosmetic purposes. All the participants were females and represented a range of age groups from the 20s to above 60s. Items in the nonstandardized questionnaire elicited questions relating to the reasons for and against BT use. STATISTICAL ANALYSIS USED: Descriptive analysis was used rather than inferential statistics, and involved ranking the responses according to the most likely reasons for using BT and disadvantages of its use. RESULTS: In general, the primary motivating factor for BT use was to improve self-esteem, and the greatest disadvantage involved financial costs associated with the procedure. CONCLUSIONS: The main findings of this study suggest that females who use BT for aesthetic purposes are motivated by personal psychological gains (intrapersonal attributes) rather than social gains (interpersonal factors). In other words, they do not believe that having BT will equate to being treated any better by other people but would rather provide them with confidence and satisfaction regarding their self-image. PMID- 26865792 TI - Complications of skin biopsy. AB - Skin biopsy is the most commonly performed procedure by the dermatologist. Though it is a safe and easy procedure yet complications may arise. Post operative complications like wound infection and bleeding may occur. It is essential to keep the potential complications of skin biopsy in mind and be meticulous in the technique, for better patient outcomes. PMID- 26865793 TI - Chondroid Syringoma of the Philtral Dimple. AB - A chondroid syringoma (CS) is an exceedingly rare mixed tumor of the skin. These tumors are relatively common in the head and neck area. Occurrence of these tumors in the philtrum is rare, with only two documented cases in English literature to the best of our knowledge. This paper presents a case of CS of the philtral dimple with aesthetically excellent philtrum reconstruction. PMID- 26865794 TI - Successful Treatment of Recalcitrant Bowen's Disease of the Lower Back Using a Bimodal Approach. PMID- 26865795 TI - An Uncommon Complication of Hair Transplant: A Crack in the "Slit". PMID- 26865796 TI - Erratum: Successful Treatment of Tattoo-Induced Pseudolymphoma with Sequential Ablative Fractional Resurfacing Followed by Q-Switched Nd: YAG 532 nm Laser. AB - [This corrects the article on p. 226 in vol. 6, PMID: 24470721.]. PMID- 26865797 TI - Customized Orbital Decompression Surgery Combined with Eyelid Surgery or Strabismus Surgery in Mild to Moderate Thyroid-associated Ophthalmopathy. AB - PURPOSE: To evaluate the efficacy and safety of customized orbital decompression surgery combined with eyelid surgery or strabismus surgery for mild to moderate thyroid-associated ophthalmopathy (TAO). METHODS: Twenty-seven consecutive subjects who were treated surgically for proptosis with disfigurement or diplopia after medical therapy from September 2009 to July 2012 were included in the analysis. Customized orbital decompression surgery with correction of eyelid retraction and extraocular movement disorders was simultaneously performed. The patients had a minimum preoperative period of 3 months of stable range of ocular motility and eyelid position. All patients had inactive TAO and were euthyroid at the time of operation. Preoperative and postoperative examinations, including vision, margin reflex distance, Hertel exophthalmometry, ocular motility, visual fields, Goldmann perimetry, and subject assessment of the procedure, were performed in all patients. Data were analyzed using paired t-test (PASW Statistics ver. 18.0). RESULTS: Forty-nine decompressions were performed on 27 subjects (16 females, 11 males; mean age, 36.6 +/- 11.6 years). Twenty-two patients underwent bilateral operations; five required only unilateral orbital decompression. An average proptosis of 15.6 +/- 2.2 mm (p = 0.00) was achieved, with a mean preoperative Hertel measurement of 17.6 +/- 2.2 mm. Ocular motility was corrected through recession of the extraocular muscle in three cases, and no new-onset diplopia or aggravated diplopia was noted. The binocular single vision field increased in all patients. Eyelid retraction correction surgery was simultaneously performed in the same surgical session in 10 of 49 cases, and strabismus and eyelid retraction surgery were performed in the same surgical session in two cases. Margin reflex distance decreased from a preoperative average of 4.3 +/- 0.8 to 3.8 +/- 0.5 mm postoperatively. CONCLUSIONS: The customized orbital decompression procedure decreased proptosis and improved diplopia, in a range comparable to those achieved through more stepwise techniques, and had favorable cosmetic results when combined with eyelid surgery or strabismus surgery for mild to moderate TAO. PMID- 26865798 TI - Periorbital Lipogranuloma after Facial Autologous Fat Injection and Its Treatment Outcomes. AB - PURPOSE: To investigate periorbital lipogranuloma cases that developed after autologous fat injection and to determine various treatment outcomes from these cases. METHODS: This retrospective study involved 27 patients who presented with periocular mass (final diagnosis of lipogranuloma) and had history of facial autologous fat injection. The collected data included information on patient sex, age, clinical presentation, number and site of fat injections, interval between injections, duration from injection to symptom onset, fat harvesting site, use of cryopreservation, and treatment outcome. RESULTS: The most common presenting symptom was palpable mass (92.6%), followed by blepharoptosis and eyelid edema. The mean time from injection to symptom onset was 13.6 +/- 29.2 months (range, 2 to 153 months). Patients were managed by intralesional triamcinolone injection (six patients) and surgical excision (three patients); 18 patients were followed without treatment. Among the six patients who underwent intralesional triamcinolone injection, five showed complete resolution, and one showed partial resolution. Among the 18 patients who were followed without management, three showed spontaneous resolution over a 5-month follow-up period. CONCLUSIONS: Lipogranuloma can develop in the eyelid after autologous fat injection into the face. Both surgical excision and intralesional triamcinolone injection yield relatively good outcomes. Simple observation can be a good option because spontaneous resolution can occur in a subset of patients. PMID- 26865799 TI - Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration. AB - PURPOSE: To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. METHODS: This was a retrospective study. Twenty-one treatment-naive patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. RESULTS: Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. CONCLUSIONS: FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular endothelial growth factor therapy regardless of CNV lesion type. PMID- 26865800 TI - Effect of Posterior Subtenon Triamcinolone Acetonide Injection on Diabetic Macular Edema Refractory to Intravitreal Bevacizumab Injection. AB - PURPOSE: To evaluate the effects of posterior subtenon triamcinolone acetonide injection on refractory diabetic macular edema (DME) after intravitreal bevacizumab (IVB) injection failure. METHODS: Patients with DME and central subfield thickness (CST) >300 um who did not respond to IVB injections were retrospectively included. Specifically, we enrolled patients who were diagnosed with refractory DME and who experienced an increase in CST after 1 to 2 IVB injections or no decrease after >=3 consecutive IVB injections. One clinician injected 20 mg of triamcinolone acetonide into the posterior subtenon space. All patients received ophthalmic examinations at baseline and at 2, 4, and 6 months post-baseline. Examinations included Snellen visual acuity, intraocular pressure, and spectral-domain optical coherence tomography. RESULTS: Forty eyes of 34 patients were included. The average baseline CST was 476 um. The average CST decreased to 368 um at 2 months, 374 um at 4 months, and 427 um at 6 months (p < 0.001 for all results, Wilcoxon signed-rank test). The average intraocular pressure increased from 15.50 to 16.92 mmHg at 2 months but decreased to 16.30 mmHg at 4 months and 15.65 mmHg at 6 months. Logarithm of the minimum angle of resolution visual acuity improved from 0.56 to 0.50 at 2 months (p = 0.023), 0.50 at 4 months (p = 0.083), and 0.48 at 6 months (p = 0.133, Wilcoxon signed-rank test). No complications were detected. CONCLUSIONS: Posterior subtenon triamcinolone acetonide is an effective and safe treatment for reducing CST in DME refractory to IVB. PMID- 26865801 TI - Macular Choroidal Thickness and Volume Measured by Swept-source Optical Coherence Tomography in Healthy Korean Children. AB - PURPOSE: To evaluate the thickness and volume of the choroid in healthy Korean children using swept-source optical coherence tomography. METHODS: We examined 80 eyes of 40 healthy children and teenagers (<18 years) using swept-source optical coherence tomography with a tunable long-wavelength laser source. A volumetric macular scan protocol using the Early Treatment Diabetic Retinopathy Study grid was used to construct a choroidal thickness map. We also examined 44 eyes of 35 healthy adult volunteers (>=18 years) and compared adult measurements with the findings in children. RESULTS: The mean age of the children and teenagers was 9.47 +/- 3.80 (4 to 17) vs. 55.04 +/- 12.63 years (36 to 70 years) in the adult group (p < 0.001, Student's t-test). Regarding the Early Treatment Diabetic Retinopathy Study subfields, the inner temporal subfield was the thickest (247.96 um). The inner and outer nasal choroid were thinner (p = 0.004, p = 0.002, respectively) than the surrounding areas. The mean choroidal volumes of the inner and outer nasal areas were smaller (p = 0.004, p = 0.003, respectively) than those of all the other areas in each circle. Among the nine subfields, all areas in the children, except the outer nasal subfield, were thicker than those in adults (p < 0.05). Regression analysis showed that age, axial length, and refractive error correlated with subfoveal choroidal thickness (p < 0.05). CONCLUSIONS: Overall macular choroidal thickness and volume in children and teenagers were significantly greater than in adults. The nasal choroid was significantly thinner than the surrounding areas. The pediatric subfoveal choroid is prone to thinning with increasing age, axial length, and refractive error. These differences should be considered when choroidal thickness is evaluated in children with chorioretinal diseases. PMID- 26865802 TI - Comparison of the Progression of High- and Low-tension Glaucoma as Determined by Two Different Criteria. AB - PURPOSE: To investigate and compare the progression of medically treated primary open angle glaucoma according to the baseline intraocular pressure (IOP). METHODS: This study included a total of 345 eyes from 345 patients (mean follow up period, 4.5 years). Eyes were classified into either conventional normal tension glaucoma (cNTG, <=21 mmHg) or conventional high-tension glaucoma (cHTG, >21 mmHg) groups according to the conventional cut-off value of the IOP. Additionally, the median IOP (15 mmHg) was used to create two other groups (median NTG [mNTG] <=15 mmHg and median HTG [mHTG] >15 mmHg). Using these values, 306, 39, 153, and 192 eyes were assigned to the cNTG, cHTG, mNTG, and mHTG groups, respectively. Glaucoma progression was determined either by optic disc/retinal nerve fiber layer photographs or serial visual field data. RESULTS: Mean reduction of IOP after medical treatment and of central corneal thickness was lower in the cNTG group, while the prevalence of disc hemorrhage and baseline visual field mean deviation did not differ between the cNTG and cHTG groups. A mean reduction in the IOP was observed after medical treatment, and central corneal thickness was lower in the mNTG group; disc hemorrhage was more frequent in the mNTG than in the mHTG group. Among the 345 analyzed eyes, 100 (29%) showed progression during the follow-up period. In the cHTG group, a higher baseline IOP (hazard ratio, 1.147; p = 0.024) was associated with glaucoma progression. Disc hemorrhage (hazard ratio, 15.533; p < 0.001) was also strongly associated with progression in the mNTG group. CONCLUSIONS: Baseline IOP was a significant risk factor for glaucoma progression in cHTG patients (10% of our total participants), while disc hemorrhage showed the strongest association with progression in the mNTG group, indicating that a cut-off value other than the conventional 21 mmHg is required to define true low-tension glaucoma in populations where NTG predominates among all glaucoma patients. PMID- 26865803 TI - Comparison of Postoperative Exodrift after First Unilateral and Second Contralateral Lateral Rectus Recession in Recurrent Exotropia. AB - PURPOSE: To compare postoperative exodrift of the first unilateral lateral rectus (ULR) muscle recession with the exodrift of the second contralateral ULR muscle recession in patients with recurrent small-angle exotropia (XT). METHODS: We evaluated the results of a second ULR muscle recession in 19 patients with recurrent XT with deviation angles under 25 prism diopter (PD), following a first procedure of ULR muscle recession for small-angle XT. Recession of the lateral rectus muscle ranged from 8 to 9 mm. The postoperative motor alignment and degree of exodrift were investigated after the first ULR muscle recession and the second ULR muscle recession in the same patients. RESULTS: Observed differences in postoperative ocular alignment between the first ULR muscle recession and the second ULR muscle recession were statistically significant at follow-up periods of six months (7.84 +/- 4.43 vs. 3.89 +/- 3.47 PD), one year (9.58 +/- 4.97 vs. 5.21 +/- 4.94 PD), and at a final follow-up (21.11 +/- 2.98 vs. 7.52 +/- 4.06 PD) after surgery (p = 0.006, 0.013, and 0.000). Postoperative exodrift was statistically different between the first and second ULR muscle recessions at three to six months (2.89 +/-3.75 vs. 0.63 +/- 3.45 PD) and one year to final follow-up (11.52 +/- 5.50 vs. 2.32 +/- 3.53 PD) (p = 0.034 and 0.000). All of the first ULR muscle recession patients showed XT with deviation angles of more than 15 PD at the final follow-up. Regardless, the surgical success rate (<8 PD) after the second ULR recession was 63.16% (12 patients) among the total amount of patients with recurrent XT. CONCLUSIONS: This study shows that changes in exodrift after a second ULR muscle recession are less than changes after the first URL muscle recession among patients with recurrent XT. A second ULR muscle recession may be a useful surgery for small-angle XT patients with deviation angles of 25 PD or less after a first ULR muscle recession. PMID- 26865804 TI - Higher Order Aberration and Astigmatism in Children with Hyperopic Amblyopia. AB - PURPOSE: To investigate the changes in corneal higher-order aberration (HOA) during amblyopia treatment and the correlation between HOA and astigmatism in hyperopic amblyopia children. METHODS: In this retrospective study, a total of 72 eyes from 72 patients ranging in age from 38 to 161 months were included. Patients were divided into two groups based on the degree of astigmatism. Corneal HOA was measured using a KR-1W aberrometer at the initial visit and at 3-, 6-, and 12-month follow-ups. Correlation analysis was performed to assess the association between HOA and astigmatism. RESULTS: A total of 72 patients were enrolled in this study, 37 of which were classified as belonging to the higher astigmatism group, while 35 were assigned to the lower astigmatism group. There was a statistically significant difference in success rate between the higher and lower astigmatism groups. In both groups, all corneal HOAs were significantly reduced during amblyopia treatment. When comparing the two groups, a significant difference in coma HOA at the 12-month follow-up was detected (p = 0.043). In the Pearson correlation test, coma HOA at the 12-month follow-up demonstrated a statistically significant correlation with astigmatism and a stronger correlation with astigmatism in the higher astigmatism group than in the lower astigmatism group (coefficient values, 0.383 and 0.284 as well as p = 0.021 and p = 0.038, respectively). CONCLUSIONS: HOA, particularly coma HOA, correlated with astigmatism and could exert effects in cases involving hyperopic amblyopia. PMID- 26865805 TI - The Stabilization of Postoperative Exo-drift in Intermittent Exotropia after Surgical Treatment. AB - PURPOSE: To investigate the long-term clinical course of intermittent exotropia after surgical treatment to determine whether and when postoperative exo-drift stabilizes, and the required postsurgery follow-up duration in cases of intermittent exotropia. METHODS: We retrospectively reviewed the medical records of patients diagnosed with intermittent exotropia who underwent surgical treatment between January 1992 and January 2006 at Yeungnam University Hospital and postoperatively performed regular follow-up examinations for up to 7 years. We also analyzed the difference in exo-drift stabilization, according to surgical procedure. RESULTS: A total of 101 patients were enrolled in the study. Thirty one patients underwent lateral rectus recession and medial rectus resection (R&R) and 70 patients underwent bilateral lateral rectus recession (BLR). The postoperative angles of deviation increased significantly during the initial 36 months, but no subsequent significant changes were observed for up to 84 months. Follow-ups for 7 years revealed that more than 50% of the total amount of exo drift was observed within the first postoperative year. In addition, the angles of deviation at 1 year correlated with those at 7 years postoperatively (Pearson correlation coefficient r = 0.517, p < 0.001). No significant exo-drift was observed after 36 months in patients who underwent BLR, whereas after 18 months in patients who underwent R&R. CONCLUSIONS: The minimum postoperative follow-up required after surgical treatment to ensure stable results is 36 months. In particular, careful follow-up is necessary during the first postoperative year to detect rapid exo-drift. Patients who underwent BLR required a longer follow-up than those who underwent R&R to ensure stable postoperative alignment. PMID- 26865807 TI - Brown-McLean Syndrome in a Patient with Hallermann-Streiff Syndrome. PMID- 26865806 TI - Effect of Nitric Oxide on the Expression of Matrix Metalloproteinase and Its Association with Migration of Cultured Trabecular Meshwork Cells. AB - PURPOSE: To determine the effect of exogenous nitric oxide (NO) on the migration of trabecular meshwork (TM) cells and its association with expression of matrix metalloproteinases (MMPs). METHODS: Primary human TM cells treated with 1 or 10 uM S-nitroso-N-acetyl-penicillamine (SNAP) and examined for changes in adherence. TM cells were seeded onto transwell culture inserts, and changes in their migratory activity were quantified. Reverse transcription polymerase chain reaction was performed to determine the relative changes in mRNA expression of MMPs and tissue inhibitor of metalloproteinases (TIMPs). RESULTS: Treatment with SNAP did not significantly suppress TM cell adhesion or migration (p > 0.05). Treatment of TM cells with 10 uM SNAP decreased expression of MMP-2 and increased expression of membrane type MMP-1 and TIMP-2. Treatment with interleukin-1alpha triggered MMP-3 expression but did not exert significant effects on MMP-3 activation in response to SNAP. CONCLUSIONS: These data suggest that NO revealed no significant effect on the migration of TM cells because NO decreased MMP-2 and increased TIMP-2 expression. Although expression of certain MMPs and TIMPs change in response to NO donors, NO may modulate trabecular outflow by changing the cellular production of extracellular matrix without having a significant effect on the migration of TM cells. PMID- 26865808 TI - Comment on: Choroidal Blood Flow Change in Eyes with High Myopia. PMID- 26865809 TI - Optic Fracture of the Preloaded Intraocular Lens during Insertion. PMID- 26865810 TI - Bietti Crystalline Retinopathy Confirmed by Mutation of CYP4V2 Gene in a Korean Patient. PMID- 26865811 TI - "We are Arabs:" The Embodiment of Virginity Through Arab and Arab American Women's Lived Experiences. AB - Virginity is part of our existence in the world as embodied sexual subjects. While many meanings are associated with virginity, in most of the Arab world virginity relates to the presence of a hymen and extends to encompass the honor of the Arab community, and virginity loss commonly relate to first vaginal intercourse. This study explored the meanings of virginity from the perspectives of Arab and Arab American women. A qualitative phenomenological approach, informed by the philosophy of Maurice Merleau-Ponty, was used to conduct in-depth interviews with ten women. We identified one over-arching theme Virginity as Identity, and two major themes Embodiment of Virginity and "We are Arabs." To reach an embodied virginity, participants went through a disembodied virginity process, reflecting society's perceptions and values of virginity related to anatomical presence of a hymen and society's honor. "We are Arabs" describes the ways women identified with the Arab ethnic identity as a shared overall identification, but differed from one lived experience to another, and influenced how participants embodied virginity. Our participants provided a better understanding of the diverse meanings of virginity that move beyond the binary of virginity and virginity loss, and into a spectrum of embodied meanings. Findings suggest the need for future research around sexuality in Arab Americans with attention to socio-political contexts in order to understand the nature and context of sexual initiation and its impact on sexual behaviors and well-being. PMID- 26865813 TI - New record and redescription of Calanopia thompsoni A. Scott, 1909 (Copepoda, Calanoida, Pontellidae) from the Red Sea, with notes on the taxonomic status of C. parathompsoni Gaudy, 1969 and a key to species. AB - During a plankton sampling programme around Al-Wajh area, Saudi Arabian coast of the northern Red Sea, a copepod Calanopia thompsoni A. Scott, 1909 (Calanoida: Pontellidae) was reported for the first time in the Red Sea. Both sexes are fully redescribed and compared to previous descriptions as well as the closely related species, Calanopia parathompsoni. The zoogeographical distribution of the species confirms that it is of Indo-Pacific origin. A dichotomous key for the identification of males and females of the species of Calanopia is included. PMID- 26865812 TI - On the uncertainty beneath the name Oithona similis Claus, 1866 (Copepoda, Cyclopoida). AB - The marine cyclopoid Oithona similis sensu lato Claus, 1866, is considered to be one of the most abundant and ubiquitous copepods in the world. However, its minimal original diagnosis and the unclear connection with its (subjective) senior synonym Oithona helgolandica Claus, 1863, may have caused frequent misidentification of the species. Consequently, it seems possible that several closely related but distinct forms are being named Oithona similis or Oithona helgolandica without explicit and accurate discrimination. Here the current situation concerning the correct assignment of the two species is revised, the morphological characters commonly used to identify and distinguish each species are summarized, and the nomenclatural implications of indiscriminately using these names in current taxonomic and ecological practice is considered. It is not intended to upset a long-accepted name in its accustomed meaning but certainly the opposite. "In pursuit of the maximum stability compatible with taxonomic freedom" (International Commission of Zoological Nomenclature), we consider that reassessment of the diagnostic characters of Oithona similis sensu stricto cannot be postponed much longer. While a consensus on taxonomy and nomenclatural matters can be attained, we strongly recommend specifically reporting the authority upon which the identification of either Oithona similis s.l. or Oithona helgolandica s.l. has been accomplished. PMID- 26865814 TI - New records of Protura (Entognatha, Arthropoda) from Romania, with an identification key to the Romanian species. AB - The Romanian Protura were studied based on 175 specimens collected from Romania, along with bibliographic data. The main publication on the Romanian proturans was written by M.A. Ionescu (1951), who described 13 species mainly from soil and forest litter from 15 collecting points. The current paper represents the first study at a national level. Faunal data on Protura were obtained from 22 sites, mostly from forests of the Romanian Carpathians and also from a peri-urban area of Bucharest, which had not been studied before. As a result, the Romanian Protura fauna now consists of 27 known taxa in 6 genera and 4 families. Of the 27 taxa, 15 species are new records for Romanian fauna. An identification key to the Romanian Protura species is provided. PMID- 26865815 TI - Nylanderia deceptrix sp. n., a new species of obligately socially parasitic formicine ant (Hymenoptera, Formicidae). AB - Obligately socially parasitic ants are social parasites that typically lack the sterile worker caste, and depend on the host species for survival and brood care. The genus Nylanderia has over 130 described species and subspecies, none of which, until this study, were known social parasites. Here we describe the first social parasite known in the genus, Nylanderia deceptrix. Aspects of the biology of the host species, Nylanderia parvula (Mayr 1870), and Nylanderia deceptrix are examined. The data from both the host and the parasite species are combined to better understand the host-parasite relationship. PMID- 26865816 TI - A taxonomy review of Oreoderus Burmeister, 1842 from China with a geometric morphometric evaluation (Coleoptera, Scarabaeidae, Valgini). AB - The species of the genus Oreoderus are morphologically similar, and can be challenging to distinguish without dissecting the male genitalia. In this study, the Oreoderus species from China are reviewed. Three new species of Oreoderus are described: Oreoderus dasystibialis Li & Yang, sp. n., Oreoderus brevitarsus Li & Yang, sp. n. and Oreoderus oblongus Li & Yang, sp. n. A key of the male Oreoderus and a distribution map are provided. Oreoderus coomani Paulian, 1961 was found as a new record in China. The first description of the female of Oreoderus arrowi Ricchiardi, 2001 is provided. Oreoderus humeralis Gestro, 1891, Oreoderus quadricarinatus Arrow, 1944, Oreoderus crassipes Arrow, 1944, and Oreoderus momeitensis Arrow, 1910 are excluded from the Chinese fauna. Furthermore, we utilize geometric morphometric approaches (GM) to analyze the shape variation of four characters (pronotum, elytra, protibia and aedeagus) in Oreoderus. The morphological variations of Oreoderus and the taxonomic value of each character are discussed. The combined analysis of geometric morphometrics and comparative morphology support recognition of the three new species. PMID- 26865817 TI - Revision of the subgenus Orthoscymnus Canepari of Scymnus Kugelann (Coleoptera, Coccinellidae), with descriptions of four new species. AB - The subgenus Orthoscymnus Canepari, 1997 of Scymnus Kugelann, 1794 is herein revised. Seven species of the Orthoscymnus fauna are recognized, of which four species, Scymnus (Orthoscymnus) jilongicus sp. n., Scymnus (Orthoscymnus) paradoxus sp. n., Scymnus (Orthoscymnus) crispatus sp. n. and Scymnus (Orthoscymnus) duomaculatus sp. n., are described as new to science. Scymnus (Orthoscymnus) rhododendri Canepari is recorded from China for the first time. Scymnus (Pullus) robustibasalis Yu is transferred to the subgenus Orthoscymnus (comb. n.). All species are diagnosed, described and illustrated, and distributions are provided for each species. A key to the species is included. PMID- 26865818 TI - Further contributions to the longhorn beetle (Coleoptera, Cerambycidae) fauna of New Brunswick and Nova Scotia, Canada. AB - Sixteen species of Cerambycidae are newly recorded for New Brunswick, Canada; Arhopalus obsoletus (Randall), Atimia confusa confusa (Say), Callidium frigidum Casey, Phymatodes amoenus (Say), Phymatodes testaceus (Linnaeus), Neoclytus mucronatus mucronatus (Fabricius), Xylotrechus aceris Fisher, Xylotrechus sagittatus sagittatus (Germar), Tylonotus bimaculatus Haldeman, Lepturges angulatus (LeConte), Lepturges symmetricus (Haldeman), Urgleptes querci (Fitch), Oplosia nubila (LeConte), Eupogonius subarmatus (LeConte), Monochamus carolinensis (Olivier), and Pogonocherus parvulus LeConte. Urgleptes signatus (LeConte) and Urgleptes querci are newly recorded from Nova Scotia. All but two specimens were collected in 12-funnel Lindgren traps. Xylotrechus aceris, Tylonotus bimaculatus, Lepturges angulatus, Lepturges symmetricus, Urgleptes signatus (NS), and Pogonocherus parvulus were detected exclusively in traps deployed in the forest canopy, and most individuals of Oplosia nubila and Monochamus carolinensis were captured in canopy traps. Arhopalus obsoletus, Atimia confusa confusa, Callidium frigidum, Phymatodes testaceus, and Xylotrechus sagittatus sagittatus were captured almost exclusively in traps near (1 m above) the forest floor. These results highlight the importance of sampling both the understory and upper canopy when using traps for surveying diversity of Cerambycidae. PMID- 26865819 TI - Two new species of spotted Hypancistrus from the Rio Negro drainage (Loricariidae, Hypostominae). AB - Two new species, Hypancistrus phantasma and Hypancistrus margaritatus, are described based on material from the Rio Negro drainage. Both species are distinguished from congeners by unique color patterns. Hypancistrus phantasma is described from the Rio Uaupes and differs from congeners by having a tan body with small dark spots (vs. dark with light spots or with saddles or stripes). Hypancistrus margaritatus is described from the Takutu River and differs from congeners by having densely-packed light spots on a dark brown background, with spots about the size of the nasal aperture (vs. sparse light spots either smaller or larger than the nasal aperture, or brown to black spots, saddles, or stripes). PMID- 26865820 TI - Dataset of Passerine bird communities in a Mediterranean high mountain (Sierra Nevada, Spain). AB - In this data paper, a dataset of passerine bird communities is described in Sierra Nevada, a Mediterranean high mountain located in southern Spain. The dataset includes occurrence data from bird surveys conducted in four representative ecosystem types of Sierra Nevada from 2008 to 2015. For each visit, bird species numbers as well as distance to the transect line were recorded. A total of 27847 occurrence records were compiled with accompanying measurements on distance to the transect and animal counts. All records are of species in the order Passeriformes. Records of 16 different families and 44 genera were collected. Some of the taxa in the dataset are included in the European Red List. This dataset belongs to the Sierra Nevada Global-Change Observatory (OBSNEV), a long-term research project designed to compile socio ecological information on the major ecosystem types in order to identify the impacts of global change in this area. PMID- 26865821 TI - Polymerase Chain Reaction: A Better Method for Diagnosing Chronic Schistosoma mansoni Infections. AB - For more effective diagnosis of the acute and chronic stages of Schistosoma mansoni infection in humans, the polymerase chain reaction (PCR) technique was compared with the Kato-Katz method. A total of 150 stool samples were collected from inpatient and outpatient clinics at the Department of Tropical Medicine, Minia University Hospital, Egypt. Three groups of patients, 50 with acute intestinal schistosomiasis, 70 with chronic intestinal schistosomiasis and 30 normal healthy controls were studied. Stool samples were analyzed by PCR and the Kato-Katz method. The mean number of eggs per gram of feces was 4.6 when estimated by the Kato-Katz method in positive stool samples from acute schistosomiasis cases but only 1.7 in chronic cases. In acute intestinal schistosomiasis, 15 and 45 out of 50 cases were positive by Kato-Katz and PCR, respectively. In the chronic intestinal schistosomiasis cases, 6 and 68 out of 70 cases were positive by the Kato-Katz and PCR methods, respectively. We conclude that PCR appears to be an effective diagnostic technique for S. mansoni infection, especially where a low worm burden exists, such as in chronic cases. PMID- 26865822 TI - Cyclospora Infection among School Children in Kathmandu, Nepal: Prevalence and Associated Risk Factors. AB - BACKGROUND: The intestinal coccidian protozoa Cyclospora cayetanensis has emerged as an important cause of parasitic diarrhea among children living in developing countries. This study aimed to determine the prevalence of Cyclospora among the school children of Kathmandu with reference to various associated risk factors. METHODOLOGY: A total of five hundred and seven stool samples from students between the age of 3-14 years, studying in 13 different schools in Kathmandu were collected during the study period (May-November, 2014) and processed at the Public Health Research Laboratory, Institute of Medicine, Kathmandu, Nepal. A modified acid fast staining technique (Kinyoun's method) was used to detect oocyst of Cyclospora from the formal-ether concentrated stool samples. RESULTS: Cyclospora was detected in 3.94% (20/507) of the stool samples examined. The prevalence was found to be highest among the students in the 3-5 year age group i.e. 10.15% (13/128), peaking during the rainy season (June-August). The detection rate was found to be significantly higher (p < 0.05) among children presenting with diarrheal symptoms, household keeping livestock and consumers of raw vegetables/fruits, showing a prevalence of 10.57% (11/104), 10.11% (9/89) and 7.25% (14/193) respectively. CONCLUSION: Consumption of untreated drinking water, fresh produce (raw fruits/vegetables) without proper washing and the presence of livestock at home were found to be predisposing factors for higher susceptibility of infection due to Cyclospora. This finding confirms the existence of a public health issue with potentially serious consequences whereby children can be infected through exposure to oocysts in contaminated food and water and get ill as a result. PMID- 26865823 TI - Questing Amblyomma mixtum and Haemaphysalis juxtakochi (Acari: Ixodidae) Infected with Candidatus "Rickettsia amblyommii" from the Natural Environment in Panama Canal Basin, Panama. AB - This work emphasizes the detection of Candidatus "Rickettsia amblyommii" in questing Haemaphysalis juxtakochi and Amblyomma mixtum. From February 2009 to December 2012, questing ticks were collected from the vegetation and leaf-litter of four protected forests and two grassy areas around the Panama Canal basin. DNA was extracted from Amblyomma mixtum, Amblyomma naponense, Amblyomma oblongoguttatum, Amblyomma pecarium, Amblyomma tapirellum, Haemaphysalis juxtakochi, and unidentified immature Amblyomma. Specific primers of citrate synthase gene gltA were used to detect and identify the rickettsiae. Amplicons with the expected band size were purified and sequenced. DNA of C. "R. amblyommii" was found in A. mixtum, H. juxtakochi and Amblyomma immatures. To our knowledge, these finding represent the first report of C. "R. amblyommii" in free living ticks in the wilderness of Central America. PMID- 26865824 TI - Occupational Stress among Textile Workers in the Democratic Republic of Congo. AB - CONTEXT: In the Democratic Republic of Congo (DRC), scientific studies on occupational health are scarce. The present study aims at estimating the level of occupational stress, as well as associated factors, in a textile company. METHODS: We performed a cross-sectional survey among textile workers in DRC. Data (N = 192 subjects) were collected through a self-questionnaire validated for the assessment of stress (Karasek and Siegrist's scale); supplemented by a medical examination. Frequencies and odds ratios (ORs) were estimated for descriptive analyses. Adjusted ORs were calculated through a logistic regression model to investigate associations between socio-demographic and organisational variables and stress. RESULTS: Our study highlighted a high level of stress among individuals: 28% of them were suffering from stress, according to Karasek, and 22%, when applying Siegrist's model. A 14%-isostrain was calculated when considering all workers. A statistically significant association was observed between stress and age, seniority and perceived non-adaptation to work, considering both approaches. Furthermore, when job strain was determined according to Karasek, it was related to the worker status, the poor perception of organisation and alcohol consumption, while stress estimated by applying Siegrist's model showed an association with education level and the occurrence of cardiac symptoms. CONCLUSION: The present study provides of stress among individuals through both models. Several socio-professional factors are associated with stress, which determines populations at risk. The results revealed that both stress models offer complementary information, thus increasing the probability to model workers' health more exactly and to make recommendations on prevention and management. PMID- 26865825 TI - NS1' Protein Expression in the JaOArS982 Strain of Japanese Encephalitis Virus Does Not Enhance Virulence in Mice. AB - Using a mouse model, we previously demonstrated that subcutaneous infection with the JaTH160 strain of Japanese encephalitis virus (JEV) causes significantly higher virulence and stronger virus propagation in the brain compared with that of the JaOArS982 strain. We also showed that the JaTH160 strain, but not JaOArS982, expresses the NS1' protein and that NS1' enhances JEV production in avian cells and embryonated chicken eggs. In this study, we examined whether NS1' expression affects virulence in mice infected with the JaOArS982 and JaTH160 strains using the corresponding recombinant viruses S982-IC and JaTH-IC. Expression of the NS1' protein in S982-IC diminished the mortality in mice, whereas S982-IC viruses without NS1' caused 40-60% mortality. However, the viral loads in the brains of these mice were not significantly different despite the dvariation in NS1' expression. JaTH-IC viruses depleted of the NS1' protein exhibited high mortality levels, similar to those of the virus expressing NS1'. Previous studies showed that the NS1' protein plays a role in the enhanced virulence of the JEV SA14 strain in mice. However, our current data suggest that NS1' protein expression in S982-IC reduces, rather than enhances, the mortality in mice. Thus, the effect of NS1' on pathogenicity in vivo may vary among virus strains. Our data also suggest that the reduced mortality resulting from NS1' expression in S982-IC is not simply due to viral replication in the brains. Further investigation is needed to uncover the mechanism by which NS1' affects pathogenicity in JEV-infected animals. PMID- 26865826 TI - "Ten Minimum Requirement": A Management Tool to Improve Quality of Healthcare Services in Lao People Democratic Republic (Lao PDR). AB - In Lao People's Democratic Republic (PDR), the mortality rate among children under 5 years of age is high (131 per 1000 live births in 2003), partly as a consequence of poor basic services provided by district hospitals. A simplified management tool, "Ten MR (Minimum Requirement)", was developed in Lao PDR. The tool assured the quality of health services including the processes of planning, implementing, self-monitoring, supervision, reporting and evaluation. The tool focused on ten basic services, integrating stakeholders from district hospitals and governing agencies. Each district hospital develops feasible annual activities, assigning responsibility to people based on a consensus between hospital staff and local governing agencies. Hospitals can self-monitor their activities on a monthly basis. Supervisory visits to district hospitals by local governing agencies improved activities and communication between staff. Visualization of progress promoted the sharing of achievements between staff and highlighted activities in need of more work. In 2004, district hospitals in Vientiane and Oudomxay provinces initiated the application of the tool. These district hospitals included primary care hospitals for outpatients, emergency care and in-patients, with a capacity of 10-20 beds, providing care for a population of between 30,000 and 80,000 people. The Ministry of Health recognized the effectiveness of Ten MR and implemented the expansion of the tool to all district hospitals in Lao PDR from 2011. Ten MR benefits district hospitals and governing agencies. Ten MR focuses on the daily routine work, enhancing team work and communication among all stakeholders. PMID- 26865827 TI - Lessons from the Field Count more than Ever: The New Era of Global Health. AB - For many years, Japan has been silent on the achievements of Japan's Overseas Development Assistance program including the health improvement of foreign countries. Japan's contribution to global health communities through G8 process including Hashimoto Initiative is steadfast. On the other hand, in the field activity level, experts involved in ODA have not disclosed their achievements. However, the article by Wada et al., which describes the contents of TEN MR (Minimum Requirement), shed light on Japan's silent ODA community by disclosing Japan's achievements in global health by drawing lessons that may be applicable to other countries. Our future challenge in the global health will be how to synthesize actions that reflect the lessons learnt from the field and which show scientific evidence using established methods. PMID- 26865828 TI - Point-of-Admission Serum Electrolyte Profile of Children less than Five Years Old with Dehydration due to Acute Diarrhoea. AB - BACKGROUND/OBJECTIVE: Fluid, electrolytes and acid base disturbances are responsible for most deaths due to acute diarrhoea. The aim of this study is to describe the point-of-admission serum electrolyte profile of children with dehydration due to acute diarrhoea. METHODS: In this cross-sectional study, the serum electrolyte levels of 185 children with dehydration due to acute diarrhoea were assessed at the point of admission at the Diarrhoea Treatment and Training Unit of the University of Benin Teaching Hospital. The age of the study population ranged from 29 days to 59 months. RESULTS: Out of a total of 185 subjects, 30 (16.2%), 114 (61.6%), and 41 (22.2%) had severe, moderate and mild dehydration, respectively. In addition, hyponatraemic dehydration was the most common type of dehydration, accounting for 60.5% of cases. Metabolic acidosis and hypokalaemia occurred in 59.5% and 44.3% of cases, respectively. Only the serum bicarbonate level was significantly affected by degree of dehydration (p = 0.001). Age of more than 12 months and presence of vomiting were significantly associated with hyponatraemia (p = 0.005 & p = 0.02), while age of less than or equal 12 months and absence of vomiting were associated with metabolic acidosis (p = 0.04 & p = 0.03). CONCLUSION: The degree of dehydration appears to be a good predictor of the occurrence of metabolic acidosis while age is a risk factor for hyponatraemia and metabolic acidosis. PMID- 26865829 TI - Identification of Essential Containers for Aedes Larval Breeding to Control Dengue in Dhaka, Bangladesh. AB - Dengue fever (DF), one of the most important emerging arboviral diseases, is transmitted through the bite of container breeding mosquitoes Aedes aegypti and Aedes albopictus. A household entomological survey was conducted in Dhaka from August through October 2000 to inspect water-holding containers in indoor, outdoor, and rooftop locations for Aedes larvae. The objective of this study was to determine mosquito productivity of each container type and to identify some risk factors of households infested with Aedes larvae. Of 9,222 households inspected, 1,306 (14.2%) were positive for Aedes larvae. Of 38,777 wet containers examined, 2,272 (5.8%) were infested with Aedes larvae. Containers used to hold water, such as earthen jars, tanks, and drums were the most common containers for larval breeding. Tires in outdoor and rooftop locations of the households were also important for larval breeding. Although present in abundance, buckets were of less importance. Factors such as independent household, presence of a water storage system in the house, and fully/partly shaded outdoors were found to be significantly associated with household infestation of Aedes larvae. Identification and subsequent elimination of the most productive containers in a given area may potentially reduce mosquito density to below a level at which dengue transmission may be halted. PMID- 26865830 TI - The Cytoplasmic Region of Plasmodium falciparum SURFIN4.2 Is Required for Transport from Maurer's Clefts to the Red Blood Cell Surface. AB - BACKGROUND: Plasmodium, the causative agent of malaria, exports many proteins to the surface of the infected red blood cell (iRBC) in order to modify it toward a structure more suitable for parasite development and survival. One such exported protein, SURFIN4.2, from the parasite of human malignant malaria, P. falciparum, was identified in the trypsin-cleaved protein fraction from the iRBC surface, and is thereby inferred to be exposed on the iRBC surface. SURFIN4.2 also localize to Maurer's clefts-parasite-derived membranous structures established in the RBC cytoplasm and tethered to the RBC membrane-and their role in trafficking suggests that they are a pathway for SURFIN4.2 transport to the iRBC surface. It has not been determined the participation of protein domains and motifs within SURFIN4.2 in transport from Maurer's clefts to the iRBC surface; and herein we examined if the SURFIN4.2 intracellular region containing tryptophan-rich (WR) domain is required for its exposure on the iRBC surface. RESULTS: We generated two transgenic parasite lines which express modified SURFIN4.2, with or without a part of the intracellular region. Both recombinant SURFIN4.2 proteins were exported to Maurer's clefts. However, only SURFIN4.2 possessing the intracellular region was efficiently cleaved by surface treatment of iRBC with proteinase K. CONCLUSIONS: These results indicate that SURFIN4.2 is exposed on the iRBC surface and that the intracellular region containing WR domain plays a role on the transport from Maurer's clefts to the iRBC membrane. PMID- 26865831 TI - Disaggregated N2O emission factors in China based on cropping parameters create a robust approach to the IPCC Tier 2 methodology. AB - China accounts for a third of global nitrogen fertilizer consumption. Under an International Panel on Climate Change (IPCC) Tier 2 assessment, emission factors (EFs) are developed for the major crop types using country-specific data. IPCC advises a separate calculation for the direct nitrous oxide (N2O) emissions of rice cultivation from that of cropland and the consideration of the water regime used for irrigation. In this paper we combine these requirements in two independent analyses, using different data quality acceptance thresholds, to determine the influential parameters on emissions with which to disaggregate and create N2O EFs. Across China, the N2O EF for lowland horticulture was slightly higher (between 0.74% and 1.26% of fertilizer applied) than that for upland crops (values ranging between 0.40% and 1.54%), and significantly higher than for rice (values ranging between 0.29% and 0.66% on temporarily drained soils, and between 0.15% and 0.37% on un-drained soils). Higher EFs for rice were associated with longer periods of drained soil and the use of compound fertilizer; lower emissions were associated with the use of urea or acid soils. Higher EFs for upland crops were associated with clay soil, compound fertilizer or maize crops; lower EFs were associated with sandy soil and the use of urea. Variation in emissions for lowland vegetable crops was closely associated with crop type. The two independent analyses in this study produced consistent disaggregated N2O EFs for rice and mixed crops, showing that the use of influential cropping parameters can produce robust EFs for China. PMID- 26865833 TI - Creative interactions with data: using visual and metaphorical devices in repeated focus groups. AB - This article presents some of the emergent methods developed to fit a study of quality in inclusive research with people with learning disabilities. It addresses (i) the ways in which the methodology was a response to the need for constructive, transformative dialogue through use of repeated focus groups in a design interspersing dialogic and reflective spaces; and (ii) how stimulus materials for the focus groups involved imaginative and creative interactions with data. Particular innovations in the blending of narrative and thematic analyses and data generation and analysis processes are explored, specifically the creative use of metaphor as stimulus and the playful adaptation of I-poems from the Listening Guide approach as writing and performance. In reflecting on these methodological turns we also reflect on creativity as an interpretive lens. The paper is an invitation for further methodological dialogue and development. PMID- 26865832 TI - Modelling of amorphous cellulose depolymerisation by cellulases, parametric studies and optimisation. AB - Improved understanding of heterogeneous cellulose hydrolysis by cellulases is the basis for optimising enzymatic catalysis-based cellulosic biorefineries. A detailed mechanistic model is developed to describe the dynamic adsorption/desorption and synergistic chain-end scissions of cellulases (endoglucanase, exoglucanase, and beta-glucosidase) upon amorphous cellulose. The model can predict evolutions of the chain lengths of insoluble cellulose polymers and production of soluble sugars during hydrolysis. Simultaneously, a modelling framework for uncertainty analysis is built based on a quasi-Monte-Carlo method and global sensitivity analysis, which can systematically identify key parameters, help refine the model and improve its identifiability. The model, initially comprising 27 parameters, is found to be over-parameterized with structural and practical identification problems under usual operating conditions (low enzyme loadings). The parameter estimation problem is therefore mathematically ill posed. The framework allows us, on the one hand, to identify a subset of 13 crucial parameters, of which more accurate confidence intervals are estimated using a given experimental dataset, and, on the other hand, to overcome the identification problems. The model's predictive capability is checked against an independent set of experimental data. Finally, the optimal composition of cellulases cocktail is obtained by model-based optimisation both for enzymatic hydrolysis and for the process of simultaneous saccharification and fermentation. PMID- 26865834 TI - Quantitative assessment of placental morphology may identify specific causes of stillbirth. AB - BACKGROUND: Stillbirth is frequently the result of pathological processes involving the placenta. Understanding the significance of specific lesions is hindered by qualitative subjective evaluation. We hypothesised that quantitative assessment of placental morphology would identify alterations between different causes of stillbirth and that placental phenotype would be independent of post mortem effects and differ between live births and stillbirths with the same condition. METHODS: Placental tissue was obtained from stillbirths with an established cause of death, those of unknown cause and live births. Image analysis was used to quantify different facets of placental structure including: syncytial nuclear aggregates (SNAs), proliferative cells, blood vessels, leukocytes and trophoblast area. These analyses were then applied to placental tissue from live births and stillbirths associated with fetal growth restriction (FGR), and to placental lobules before and after perfusion of the maternal side of the placental circulation to model post-mortem effects. RESULTS: Different causes of stillbirth, particularly FGR, cord accident and hypertension had altered placental morphology compared to healthy live births. FGR stillbirths had increased SNAs and trophoblast area and reduced proliferation and villous vascularity; 2 out of 10 stillbirths of unknown cause had similar placental morphology to FGR. Stillbirths with FGR had reduced vascularity, proliferation and trophoblast area compared to FGR live births. Ex vivo perfusion did not reproduce the morphological findings of stillbirth. CONCLUSION: These preliminary data suggest that addition of quantitative assessment of placental morphology may distinguish between different causes of stillbirth; these changes do not appear to be due to post-mortem effects. Applying quantitative assessment in addition to qualitative assessment might reduce the proportion of unexplained stillbirths. PMID- 26865835 TI - Mutation pattern is an influential factor on functional mutation rates in cancer. AB - BACKGROUND: Mutation rates are consistently varied in cancer genome and play an important role in tumorigenesis, however, little has been known about their function potential and impact on the distribution of functional mutations. In this study, we investigated genomic features which affect mutation pattern and the function importance of mutation pattern in cancer. METHODS: Somatic mutations of clear-cell renal cell carcinoma, liver cancer, lung cancer and melanoma and single nucleotide polymorphisms (SNPs) were intersected with 54 distinct genomic features. Somatic mutation and SNP densities were then computed for each feature type. We constructed 2856 1-Mb windows, in which each row (1-Mb window) contains somatic mutation, SNP densities and 54 feature vectors. Correlation analyses were conducted between somatic mutation, SNP densities and each feature vector. We also built two random forest models, namely somatic mutation model (CSM) and SNP model to predict somatic mutation and SNP densities on a 1-Kb scale. The relation of CSM and SNP scores was further analyzed with the distributions of deleterious coding variants predicted by SIFT and Mutation Assessor, non-coding functional variants evaluated with FunSeq 2 and GWAVA and disease-causing variants from HGMD and ClinVar databases. RESULTS: We observed a wide range of genomic features which affect local mutation rates, such as replication time, transcription levels, histone marks and regulatory elements. Repressive histone marks, replication time and promoter contributed most to the CSM models, while, recombination rate and chromatin organizations were most important for the SNP model. We showed low mutated regions preferentially have higher densities of deleterious coding mutations, higher average scores of non-coding variants, higher fraction of functional regions and higher enrichment of disease-causing variants as compared to high mutated regions. CONCLUSIONS: Somatic mutation densities vary largely across cancer genome, mutation frequency is a major indication of function and influence on the distribution of functional mutations in cancer. PMID- 26865836 TI - Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line. AB - BACKGROUND: Breast cancer is the most prevalent malignancies among the women that have a high mortality. Previous studies demonstrated that hypericin, a bioactive component of Hypericum perforatum have a cytotoxic effect on the malignant cell lines. However, an anti-carcinogenic activity of hypericin on MCF-7 is uncertain. To investigate the cytotoxic effect of hypericin on MCF-7 cells, a human breast adenocarcinoma cell-line, that resistance to chemotherapy. METHODS: The MCF-7 and fibroblast (as normal cell line) were treated with various concentrations of hypericin, and Cisplatin as a positive control for 24 and 48 h. Cytotoxicity activity was measured and confirmed by MTT assay and Trypan blue staining, respectively. In addition, Apoptosis were determined by Annexin V/Propidium Iodide assay. Immunocytochemistry (ICC) analysis for bcl2 and p53 proteins performed to further investigate different expression of these genes in different samples. RESULTS: Both cisplatin and the hypericin exhibited a dose-dependent cytotoxic effect in the MCF-7 cell line. Although the LD50 of the hypericin was significantly lower when compared to cispaltin (5 vs. 20 MUg/ml), it continued to decrease the growth rate of the MCF-7 cells when tested at higher concentration than LD50. In contrast, cisplatine, at higher concentration than LD50, completely inhibited the growth of the MCF-7 in 48 h. Regarding Annexin V/Propidium results, treatment of MCF-7 cells with LD50 concentration of cisplatin and hypericin showed 60 and 52 % apoptosis in 24 h, respectively. ICC analysis for bcl2 and p53 also confirmed our results; in treated samples for the dose of LD50 in 24 and 48 h of cisplatin and hypercin, more cells expressed p53 (guardian of cells in front of tumor formation/progression) and less expressed bcl2 (which has anti apoptotic activity) compared to untreated samples. CONCLUSIONS: Considering that hypericin showed to be cytotoxic, it seems to be a chemopreventive agent and a good candidate for antineoplastic drug development. PMID- 26865838 TI - Editor's Introduction to This Issue. PMID- 26865837 TI - Effects of Demographics and OTC Analgesics on Ovarian Cancer Symptoms. AB - Several independent studies have shown that ovarian cancer is not a silent disease and that many women have symptoms before diagnosis. These symptoms include abdominal/pelvic pain, feeling full quickly, and bloating. However, little information is known about what personal characteristics, medical conditions, or habits influence these symptoms or how they are reported. This report evaluates and describes factors that may be associated with how a patient reports these symptoms. We show that a small number of characteristics, include race, number of gynecologic conditions, and reason for clinic visit, may influence what symptoms are reported and the specific pattern of reporting. PMID- 26865839 TI - Small Non-coding Transfer RNA-Derived RNA Fragments (tRFs): Their Biogenesis, Function and Implication in Human Diseases. AB - tRNA-derived RNA fragments (tRFs) are an emerging class of non-coding RNAs (ncRNAs). A growing number of reports have shown that tRFs are not random degradation products but are functional ncRNAs made of specific tRNA cleavage. They play regulatory roles in several biological contexts such as cancer, innate immunity, stress responses, and neurological disorders. In this review, we summarize the biogenesis and functions of tRFs. PMID- 26865840 TI - Role of Chromosome Changes in Crocodylus Evolution and Diversity. AB - The karyotypes of most species of crocodilians were studied using conventional and molecular cytogenetics. These provided an important contribution of chromosomal rearrangements for the evolutionary processes of Crocodylia and Sauropsida (birds and reptiles). The karyotypic features of crocodilians contain small diploid chromosome numbers (30~42), with little interspecific variation of the chromosome arm number (fundamental number) among crocodiles (56~60). This suggested that centric fusion and/or fission events occurred in the lineage, leading to crocodilian evolution and diversity. The chromosome numbers of Alligator, Caiman, Melanosuchus, Paleosuchus, Gavialis, Tomistoma, Mecistops, and Osteolaemus were stable within each genus, whereas those of Crocodylus (crocodylians) varied within the taxa. This agreed with molecular phylogeny that suggested a highly recent radiation of Crocodylus species. Karyotype analysis also suggests the direction of molecular phylogenetic placement among Crocodylus species and their migration from the Indo-Pacific to Africa and The New World. Crocodylus species originated from an ancestor in the Indo-Pacific around 9~16 million years ago (MYA) in the mid-Miocene, with a rapid radiation and dispersion into Africa 8~12 MYA. This was followed by a trans-Atlantic dispersion to the New World between 4~8 MYA in the Pliocene. The chromosomes provided a better understanding of crocodilian evolution and diversity, which will be useful for further study of the genome evolution in Crocodylia. PMID- 26865841 TI - Introns: The Functional Benefits of Introns in Genomes. AB - The intron has been a big biological mystery since it was first discovered in several aspects. First, all of the completely sequenced eukaryotes harbor introns in the genomic structure, whereas no prokaryotes identified so far carry introns. Second, the amount of total introns varies in different species. Third, the length and number of introns vary in different genes, even within the same species genome. Fourth, all introns are copied into RNAs by transcription and DNAs by replication processes, but intron sequences do not participate in protein coding sequences. The existence of introns in the genome should be a burden to some cells, because cells have to consume a great deal of energy to copy and excise them exactly at the correct positions with the help of complicated spliceosomal machineries. The existence throughout the long evolutionary history is explained, only if selective advantages of carrying introns are assumed to be given to cells to overcome the negative effect of introns. In that regard, we summarize previous research about the functional roles or benefits of introns. Additionally, several other studies strongly suggesting that introns should not be junk will be introduced. PMID- 26865842 TI - Analysis of Whole Transcriptome Sequencing Data: Workflow and Software. AB - RNA is a polymeric molecule implicated in various biological processes, such as the coding, decoding, regulation, and expression of genes. Numerous studies have examined RNA features using whole transcriptome sequencing (RNA-seq) approaches. RNA-seq is a powerful technique for characterizing and quantifying the transcriptome and accelerates the development of bioinformatics software. In this review, we introduce routine RNA-seq workflow together with related software, focusing particularly on transcriptome reconstruction and expression quantification. PMID- 26865844 TI - Expressional Subpopulation of Cancers Determined by G64, a Co-regulated Module. AB - Studies of cancer heterogeneity have received considerable attention recently, because the presence or absence of resistant sub-clones may determine whether or not certain therapeutic treatments are effective. Previously, we have reported G64, a co-regulated gene module composed of 64 different genes, can differentiate tumor intra- or inter-subpopulations in lung adenocarcinomas (LADCs). Here, we investigated whether the G64 module genes were also expressed distinctively in different subpopulations of other cancers. RNA sequencing-based transcriptome data derived from 22 cancers, except LADC, were downloaded from The Cancer Genome Atlas (TCGA). Interestingly, the 22 cancers also expressed the G64 genes in a correlated manner, as observed previously in an LADC study. Considering that gene expression levels were continuous among different tumor samples, tumor subpopulations were investigated using extreme expressional ranges of G64-i.e., tumor subpopulation with the lowest 15% of G64 expression, tumor subpopulation with the highest 15% of G64 expression, and tumor subpopulation with intermediate expression. In each of the 22 cancers, we examined whether patient survival was different among the three different subgroups and found that G64 could differentiate tumor subpopulations in six other cancers, including sarcoma, kidney, brain, liver, and esophageal cancers. PMID- 26865843 TI - Association of HLA Genotype and Fulminant Type 1 Diabetes in Koreans. AB - Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The HLA-DRB1*04:05-HLA-DQB1*04:01 haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at HLA-DRbeta1 position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI ,1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings. PMID- 26865845 TI - Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds. AB - Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5), Landrace (n = 13), and Duroc (n = 6). An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc.These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs) related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718) in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively. PMID- 26865846 TI - Heritability Estimated Using 50K SNPs Indicates Missing Heritability Problem in Holstein Breeding. AB - Previous studies in Holstein have shown 35% to 51.8% heritability in milk production traits, such as milk yield, fat, and protein, using pedigree data. Other studies in complex human traits could be captured by common single nucleotide polymorphisms (SNPs), and their genetic variations, attributed to chromosomes, are in proportion to their length. Using genome-wide estimation and partitioning approaches, we analyzed three quantitative Holstein traits relevant to milk production in Korean Holstein data harvested from 462 individuals genotyped for 54,609 SNPs. For all three traits (milk yield, fat, and protein), we estimated a nominally significant (p = 0.1) proportion of variance explained by all SNPs on the Illumina BovineSNP50 Beadchip (h (2) G ). These common SNPs explained approximately most of the narrow-sense heritability. Longer genomic regions tended to provide more phenotypic variation information, with a correlation of 0.46~0.53 between the estimate of variance explained by individual chromosomes and their physical length. These results suggested that polygenicity was ubiquitous for Holstein milk production traits. These results will expand our knowledge on recent animal breeding, such as genomic selection in Holstein. PMID- 26865847 TI - Building the Frequency Profile of the Core Promoter Element Patterns in the Three ChromHMM Promoter States at 200bp Intervals: A Statistical Perspective. AB - Recently, the Encyclopedia of DNA Elements (ENCODE) Analysis Working Group converted data from ChIP-seq analyses from the Broad Histone track into 15 corresponding chromatic maps that label sequences with different kinds of histone modifications in promoter regions. Here, we publish a frequency profile of the three ChromHMM promoter states, at 200-bp intervals, with particular reference to the existence of sequence patterns of promoter elements, GC-richness, and transcription starting sites. Through detailed and diligent analysis of promoter regions, researchers will be able to uncover new and significant information about transcription initiation and gene function. PMID- 26865848 TI - ERRATUM: Acknowledgments Correction. Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer. AB - [This corrects the article on p. 70 in vol. 13, PMID: 26523130.]. PMID- 26865849 TI - Brugada-type ECG associated with pectus excavatum. PMID- 26865850 TI - Right ventricular outflow tract stenting - effective palliation for Fallot's tetralogy. PMID- 26865851 TI - "Bendy" stents help negotiate hairpin intracardiac curves. AB - Simple transposition of the great arteries (TGA) occurs in 0.2 per 1000 live births. The condition is surgically repaired in the neonatal period by the arterial switch procedure (ASO) sometimes preceded by an atrial septostomy. The ASO involves transecting the great arteries and relocating them to the appropriate ventriculo-arterial (VA) connection with attachment of the disconnected coronary arteries to the aorta. In the process, the attachment of the pulmonary artery to the right ventricle involves the Le Compte manoeuvre and to achieve this the pulmonary arteries must be fully mobilised and sometimes the main pulmonary artery may require patch augmentation as well. Nevertheless, pulmonary artery stenosis (PAS) is one of the potential problems with the ASO. However, with improved surgical techniques, this has dropped from around 15% in the 1980s to less than 3%. Apart from surgical revision when PAS occurs, there are interventional options which include angioplasty and/or stent insertion. The latter is preferred in small children and works well in around 60% but may require repeat procedures. In older patients or when angioplasty fails, stent insertion can be considered. These procedures may involve negotiating tight bends in order to reach the site of stenosis. The passage of non-premounted stents may be problematic in such situations, especially with longer stents and tighter bends as they tend to slip off balloon. We describe several techniques that may facilitate such interventions, and these were utilised in an adolescent patient who had had ASO for TGA in the neonatal period. These included manually giving the mounted stent a slight bend in order to help the balloon-stent assembly negotiate hairpin bends. PMID- 26865852 TI - Free left ventricular wall rupter in a newborn. PMID- 26865853 TI - Depicting the analyses of the first National Maltese Childhood BMI study. AB - INTRODUCTION: Obesity is a chronic disease that often commences in childhood. Several publications have shown that a quarter to a third of Maltese children are overweight or obese. Malta will be the first country to measure height and weight (and hence Body Mass Index) for all school children in order to quantify the extent of the problem. METHODS: This study would include 46,000 children in 150 schools. This would be the first time that any country measured its entire childhood cohort, as opposed to sampling. Hence, it was decided to attempt to facilitate data collection and analysis with the use of bespoke spreadsheets. RESULTS: This paper will demonstrate how standard Microsoft Excel was used to accomplish this, greatly speeding up the data analysis process. CONCLUSION: Software should be prepared in advance in anticipation of large amounts of data that need to be analysed and summarised. Particular care must be taken in order to prepare the requisite graphs and tables in advance so as to process the data once and present it in a suitable format for consumption and evaluation. PMID- 26865854 TI - Combination of long-acting HIV fusion inhibitor albuvirtide and LPV/r showed potent efficacy in HIV-1 patients. AB - BACKGROUND: Long acting antiretroviral drugs represent a promising approach for chronic treatment of HIV infection. Here, we study the efficacy and safety of albuvirtide (ABT), an HIV-1 fusion inhibitor with a half life of 11-12 days in human. METHODS: ABT was evaluated in a 7-week, open-label and randomized trial, combining with LPV/r. Twenty HIV-1-infected adults were assigned to two dose groups, receiving ABT (160 or 320 mg) given weekly and LPV/r given twice daily. RESULTS: At week 7, the decline of HIV-1 RNA from baseline was 1.9 (1.3-2.3) log10 and 2.2 (1.6-2.7) log10 copies/ml, and suppression of HIV-1 RNA to below 50 copies/ml was achieved in 11.1 % (1/9) and 55.6 % (5/9) patients, for the 160 and 320 mg dose group respectively. CONCLUSION: A clear dose-efficacy correlation of ABT was demonstrated. ABT combining with LPV/r is a promising two-drug regimen to be tested in larger patient population. PMID- 26865855 TI - Geographic variation in life-history traits: growth season affects age structure, egg size and clutch size in Andrew's toad (Bufo andrewsi). AB - BACKGROUND: Environmental variation associated with season length is likely to promote differentiation in life-history traits, but has been little studied in natural populations of ectotherms. We investigated patterns of variation in egg size, clutch size, age at sexual maturity, maximum age, mean age, growth rate and adult body size in relation to growth season length among 17 populations of Andrew's toad (Bufo andrewsi) at different latitudes and altitudes in the Hengduan Mountains, western China. RESULTS: We found that egg size, age at sexual maturity, and mean age increased with decreasing length of the growth season, whereas clutch size showed a converse cline. Body size did not increase with decreasing length of the growth season, but was tightly linked to lifetime activity (i.e. the estimated number of active days during lifetime). Males and females differed in their patterns of geographic variation in growth rates, which may be the result of forces shaping the trade-off between growth and reproduction in different environments. CONCLUSIONS: Our findings suggest that growth season plays an important role in shaping variation in life-history traits in B. andrewsi across geographical gradients. PMID- 26865858 TI - Respirator masks protect health but impact performance: a review. AB - Respiratory protective masks are used whenever it is too costly or impractical to remove airborne contamination from the atmosphere. Respirators are used in a wide range of occupations, form the military to medicine. Respirators have been found to interfere with many physiological and psychological aspects of task performance at levels from resting to maximum exertion. Many of these limitations have been investigated in order to determine quantitatively how much performance decrement can be expected from different levels of respirator properties. The entire system, including respirator and wearer interactions, must be considered when evaluating wearer performances. This information can help respirator designers to determine trade-offs or managers to plan to compensate for reduced productivity of wearers. PMID- 26865856 TI - Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons. AB - BACKGROUND: Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication ("shedding") at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV 8 seropositive persons. METHODS: We quantified HHV-8 oral shedding using PCR among HHV-8 seropositive persons who collected at least 14 days of oral swabs in 22 studies on 3 continents. We excluded persons taking antivirals during sampling or any prior use of antiretrovirals in those who were HIV-infected. RESULTS: 248 participants were enrolled from the US, Peru, Cameroon, Uganda, and Kenya; 61 % were men, 58 % were HIV seropositive, and 16 % had KS. Overall, 3,123 of 10,557 samples (29.6 %) had HHV-8 detected. Quantity of virus shed was highly correlated with shedding rate, (rho = 0.72, p < 0.0001). HHV-8 was detected in >=1 sample in 55 % of participants with a median of 7 % of days in the US and Kenya, 0 % in Uganda and Peru, and 18 % in Cameroon. Median episode duration was three days, and episodes with high median quantity lasted longer (42 vs 3 days, p < 0.0001). In persons with multiple observations over time, 66 % of shedding rate variance was attributable to differences between individuals. CONCLUSIONS: In HHV-8 infected individuals from diverse settings, oral mucosal shedding rate, quantity, and duration were correlated; individual shedding was highly variable. Studies are needed to determine factors accounting for between-person variation and the relationship of HHV-8 shedding to development of associated diseases. PMID- 26865857 TI - Psychometric properties and reliability of the Assessment Screen to Identify Survivors Toolkit for Gender Based Violence (ASIST-GBV): results from humanitarian settings in Ethiopia and Colombia. AB - BACKGROUND: Refugees and internally displaced persons who are affected by armed conflict are at increased vulnerability to some forms of sexual violence or other types of gender-based violence. A validated, brief and easy-to-administer screening tool will help service providers identify GBV survivors and refer them to appropriate GBV services. To date, no such GBV screening tool exists. We developed the 7-item ASIST-GBV screening tool from qualitative research that included individual interviews and focus groups with GBV refugee and IDP survivors. This study presents the psychometric properties of the ASIST-GBV with female refugees living in Ethiopia and IDPs in Colombia. METHODS: Several strategies were used to validate ASIST-GBV, including a 3 month implementation to validate the brief screening tool with women/girls seeking health services, aged >=15 years in Ethiopia (N = 487) and female IDPs aged >= 18 years in Colombia (N = 511). RESULTS: High proportions of women screened positive for past-year GBV according to the ASIST-GBV: 50.6 % in Ethiopia and 63.4 % in Colombia. The factor analysis identified a single dimension, meaning that all items loaded on the single factor. Cronbach's alpha = 0.77. A 2-parameter logistic IRT model was used for estimating the precision and discriminating power of each item. Item difficulty varied across the continuum of GBV experiences in the following order (lowest to highest): threats of violence (0.690), physical violence (1.28), forced sex (2.49), coercive sex for survival (2.25), forced marriage (3.51), and forced pregnancy (6.33). Discrimination results showed that forced pregnancy was the item with the strongest ability to discriminate between different levels of GBV. Physical violence and forced sex also have higher levels of discrimination with threats of violence discriminating among women at the low end of the GBV continuum and coercive sex for survival among women at the mid-range of the continuum. CONCLUSION: The findings demonstrate that the ASIST-GBV has strong psychometric properties and good reliability. The tool can be used to screen and identify female GBV survivors confidentially and efficiently among IDPs in Colombia and refugees in Ethiopia. Early identification of GBV survivors can enable safety planning, early referral for treatment, and psychosocial support to prevent long-term harmful consequence of GBV. PMID- 26865859 TI - Somatic incompatibility and genetic structure of fungal crops in sympatric Atta colombica and Acromyrmex echinatior leaf-cutting ants. AB - Obligate mutualistic symbioses rely on mechanisms that secure host-symbiont commitments to maximize host benefits and prevent symbiont cheating. Previous studies showed that somatic incompatibilities correlate with neutral-marker-based genetic distances between fungal symbionts of Panamanian Acromyrmex leaf-cutting ants, but the extent to which this relationship applies more generally remained unclear. Here we showed that genetic distances accurately predicted somatic incompatibility for Acromyrmex echinatior symbionts irrespective of whether neutral microsatellites or AFLP markers were used, but that such correlations were weaker or absent in sympatric Atta colombica colonies. Further analysis showed that the symbiont clades maintained by A. echinatior and A. colombica were likely to represent separate gene pools, so that neutral markers were unlikely to be similarly correlated with incompatibility loci that have experienced different selection regimes. We suggest that evolutionarily derived claustral colony founding by Atta queens may have removed selection for strong incompatibility in Atta fungi, as this condition makes the likelihood of symbiont swaps much lower than in Acromyrmex, where incipient nests stay open because queens have to forage until the first workers emerge. PMID- 26865860 TI - Periprosthetic joint infections in modular endoprostheses of the lower extremities: a retrospective observational study in 101 patients. AB - BACKGROUND: Modular mega-endoprosthesis systems are used to bridge very large bone defects and have become a widespread method in orthopaedic surgery for the treatment of tumours and revision arthroplasty. However, the indications for the use of modular mega-endoprostheses must be carefully considered. Implanting modular endoprostheses requires major, complication-prone surgery in which the limited salvage procedures should always be borne in mind. The management of periprosthetic infection is particularly difficult and beset with problems. Given this, the present study was designed to gauge the significance of periprosthetic infections in connection with modular mega-implants in the lower extremities among our own patients. METHODS: Patients who had been fitted with modular endoprosthesis on a lower extremity at our department between September 1994 and December 2011 were examined retrospectively. A total of 101 patients with 114 modular prostheses were identified. Comprising 30 men (29.7 %) and 71 women (70.3 %), their average age at the time of surgery was 67 years (18-92 years). RESULTS: The average follow-up period was 27 months (5 months and 2 weeks to 14 years and 11 months) and the drop-out rate was about 8.8 %. Altogether, there were 19 (17.7 %) endoprosthesis infections: 3 early infections and 16 late or delayed infections. The pathogen spectrum was dominated by coagulase-negative staphylococci (36 %) and Staphylococcus aureus (16 %), including 26 % multi resistant pathogens. Reinfection occurred in 37 % of cases of infection. Tumours were followed by significantly fewer infections than the other indications. Infections were twice as likely to occur after previous surgery. CONCLUSION: In our findings modular endoprostheses (18 %) are much more susceptible to infection than primary endoprostheses (0.5-2,5 %). Infection is the most common complication alongside the dislocation of proximal femur endoprostheses. Consistent, radical surgery is essential - although even with an adequate treatment strategy, the recurrence rate is very high. Unfortunately, the functional results are frequently unsatisfactory, with amputation often being the last resort. Therefore, the indication for implantation must be carefully considered and discussed in great detail, especially in the case of multimorbid patients with previous joint infections. PMID- 26865861 TI - Primary and recurrent diffuse astrocytomas: genomic profile comparison reveals acquisition of biologically relevant aberrations. AB - BACKGROUND: Diffuse astrocytomas are characterized by their highly variable biological behavior. The possibility that tumors develop novel aberrations, with relevant biological properties, is often neglected. In this study, we present two cases of diffuse astrocytoma in which additional cytogenetic and epigenetic markers with potential influence on cell proliferation or differentiation were detected at relapse. FINDINGS: The biopsies taken from the primary and recurrent tumors of two patients were analyzed with molecular methods to detect copy number variations (CNVs), gene mutations and epigenetic changes. Both cases were characterized by the R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. Features typical of astrocytomas, such as copy-neutral loss of heterozygosity at 17p and the deletion of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, were also detected in both cases. These markers were present in the primary and recurrent lesions. Other aberrations, predominantly deletions or amplifications of chromosomal segments and the hypermethylation of gene promoters, were detected in the recurrent lesions. CONCLUSIONS: The IDH1 mutation was the primary event, as previously reported. According to our observations, the methylation of promoters constituted later events, which may have further disrupted cell proliferation and/or differentiation, together with additional CNVs. PMID- 26865863 TI - Bridging experiment and theory: a template for unifying NMR data and electronic structure calculations. AB - BACKGROUND: The testing of theoretical models with experimental data is an integral part of the scientific method, and a logical place to search for new ways of stimulating scientific productivity. Often experiment/theory comparisons may be viewed as a workflow comprised of well-defined, rote operations distributed over several distinct computers, as exemplified by the way in which predictions from electronic structure theories are evaluated with results from spectroscopic experiments. For workflows such as this, which may be laborious and time consuming to perform manually, software that could orchestrate the operations and transfer results between computers in a seamless and automated fashion would offer major efficiency gains. Such tools also promise to alter how researchers interact with data outside their field of specialization by, e.g., making raw experimental results more accessible to theorists, and the outputs of theoretical calculations more readily comprehended by experimentalists. RESULTS: An implementation of an automated workflow has been developed for the integrated analysis of data from nuclear magnetic resonance (NMR) experiments and electronic structure calculations. Kepler (Altintas et al. 2004) open source software was used to coordinate the processing and transfer of data at each step of the workflow. This workflow incorporated several open source software components, including electronic structure code to compute NMR parameters, a program to simulate NMR signals, NMR data processing programs, and others. The Kepler software was found to be sufficiently flexible to address several minor implementation challenges without recourse to other software solutions. The automated workflow was demonstrated with data from a [Formula: see text] NMR study of uranyl salts described previously (Cho et al. in J Chem Phys 132:084501, 2010). CONCLUSIONS: The functional implementation of an automated process linking NMR data with electronic structure predictions demonstrates that modern software tools such as Kepler can be used to construct programs that comprehensively manage complex, multi-step scientific workflows spanning several different computers. Automation of the workflow can greatly accelerate the pace of discovery, and allows researchers to focus on the fundamental scientific questions rather than mastery of specialized software and data processing techniques. Future developments that would expand the scope and power of this approach include tools to standardize data and associated metadata formats, and the creation of interactive user interfaces to allow real-time exploration of the effects of program inputs on calculated outputs. PMID- 26865862 TI - Chicken embryonic stem cells and primordial germ cells display different heterochromatic histone marks than their mammalian counterparts. AB - BACKGROUND: Chromatin epigenetics participate in control of gene expression during metazoan development. DNA methylation and post-translational modifications (PTMs) of histones have been extensively characterised in cell types present in, or derived from, mouse embryos. In embryonic stem cells (ESCs) derived from blastocysts, factors involved in deposition of epigenetic marks regulate properties related to self-renewal and pluripotency. In the germ lineage, changes in histone PTMs and DNA demethylation occur during formation of the primordial germ cells (PGCs) to reset the epigenome of the future gametes. Trimethylation of histone H3 on lysine 27 (H3K27me3) by Polycomb group proteins is involved in several epigenome-remodelling steps, but it remains unclear whether these epigenetic features are conserved in non-mammalian vertebrates. To investigate this question, we compared the abundance and nuclear distribution of the main histone PTMs, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in chicken ESCs, PGCs and blastodermal cells (BCs) with differentiated chicken ESCs and embryonic fibroblasts. In addition, we analysed the expression of chromatin modifier genes to better understand the establishment and dynamics of chromatin epigenetic profiles. RESULTS: The nuclear distributions of most PTMs and 5hmC in chicken stem cells were similar to what has been described for mammalian cells. However, unlike mouse pericentric heterochromatin (PCH), chicken ESC PCH contained high levels of trimethylated histone H3 on lysine 27 (H3K27me3). In differentiated chicken cells, PCH was less enriched in H3K27me3 relative to chromatin overall. In PGCs, the H3K27me3 global level was greatly reduced, whereas the H3K9me3 level was elevated. Most chromatin modifier genes known in mammals were expressed in chicken ESCs, PGCs and BCs. Genes presumably involved in de novo DNA methylation were very highly expressed. DNMT3B and HELLS/SMARCA6 were highly expressed in chicken ESCs, PGCs and BCs compared to differentiated chicken ESCs and embryonic fibroblasts, and DNMT3A was strongly expressed in ESCs, differentiated ESCs and BCs. CONCLUSIONS: Chicken ESCs and PGCs differ from their mammalian counterparts with respect to H3K27 methylation. High enrichment of H3K27me3 at PCH is specific to pluripotent cells in chicken. Our results demonstrate that the dynamics in chromatin constitution described during mouse development is not universal to all vertebrate species. PMID- 26865864 TI - Erratum to: ribosomal protein and biogenesis factors affect multiple steps during movement of the Saccharomyces cerevisiae Ty1 retrotransposon. AB - [This corrects the article DOI: 10.1186/s13100-015-0053-5.]. PMID- 26865865 TI - EURAPA moves to open access: Research trends and challenges in physical activity in old age. PMID- 26865866 TI - The application of strength and power related field tests in older adults: criteria, current status and a future perspective. AB - Leg muscle strength (LMS) and leg muscle power (LMP) are determinants of aspects of functional status and important parameters for measuring intervention effects in older adults. Field tests are often used for the evaluation of LMS and LMP in older persons. However, criteria important for the application of strength and power related field tests in older adults have not been systematically taken into account and are not yet fully listed and described in a single publication. Therefore, this paper describes criteria important for the application of strength and power related field tests in older adults. In addition, strength and power related field tests commonly used in older adults are evaluated by using the described criteria. Based on this evaluation, this paper provides a perspective on the further development of field tests. Criteria important for strength and power related field tests are: adequate accuracy, precision, concurrent validity, clinical validity, practical feasibility and pure strength or power outcomes. Commonly used strength and power related field tests do not meet all the aforementioned criteria. Therefore, further development of field tests is necessary. Mobile sensing systems are potentially useful for the evaluation of LMS and LMP in older adults. Mobile sensing systems do not have the limitations of commonly used field tests and provide important additional advantages. In particular, mobile sensing systems offer the opportunity of continuous monitoring during free-movement in the home-environment, thereby reducing the need of standardized assessments by health-care professionals. Future studies should examine the clinical validity of mobile sensing systems and evaluate the application of sensor technology in exercise-based interventions. PMID- 26865867 TI - A qualitative investigation of exercising with MS and the impact on the spousal relationship. AB - BACKGROUND: Multiple Sclerosis is an autoimmune disease that affects more than 2.3 million people around the world. Symptoms are numerous and varied, often having a profound effect on activities of daily living. While for many years individuals with MS were told to avoid exercise for fear of worsening their symptoms, recent research has emphasized the multi-faceted benefits associated with regular physical activity. Given the strain that MS can put on family and interpersonal relationships, the intention of this study was to investigate the exercise experiences of individuals with MS and the extent to which these experiences affect, or are affected by, their spousal relationship. METHODS: In depth qualitative interviews were conducted with 10 individuals, five with MS, along with each of their spouses, in order to gain a comprehensive understanding of living and exercising with the disease. An inductive approach was used to analyze the interview data. RESULTS: The results displayed the important physical, psychological, and social benefits of involvement in an exercise program. Spouses help to counteract barriers and facilitate exercise, and are well aware of the integral role they play in their partner's health and well being. Spouses also valued the increased independence they gained, in the form of reduced care-giving responsibilities and enhanced social opportunities, as a result of the improved physical function of their partner. These findings contrast the severe strain on spousal relationships that is often reported in studies on people living with MS. CONCLUSIONS: Rather than an inexorable downward decline in physical ability that is common with MS, participants spoke of a positive reversal in physical function, which has had far-reaching implications for multiple aspects of their lives, including their psychological outlook, their sense of independence, overcoming isolation, and their relationship with their spouse, all of which are identified in the literature as notable aspects of life affected by the disease. PMID- 26865868 TI - Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom). AB - BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD +/- 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time. PMID- 26865869 TI - Preliminary inconclusive results of a randomised double blinded cross-over pilot trial in long-term-care dwelling elderly assessing the feasibility of stochastic resonance whole-body vibration. AB - BACKGROUND: This randomised double-blinded controlled cross-over pilot study examined feasibility and preliminary effects of stochastic resonance whole-body vibration training applied in long term care elderly. FINDINGS: Nine long term care elderly were recruited and randomized to group A (6 Hz, Noise 4 SR-WBV/ Sham) or B (Sham / 1 Hz, Noise 1 SR-WBV). Feasibility outcomes included recruitment rate, attrition, adherence and safety. Physical performance outcomes focused on the Expanded Timed Get Up-and-Go (ETGUG) test, the Short Physical Performance Battery (SPPB), and lower extremity muscle strength. Of 24 subjects initially approached 9 started and 5 completed the study resulting in 37.5 recruitment, 44.4 attrition and 81.7 % adherence rates. No adverse events were reported. There is more evidence of improved performance levels in the SR-WBV treatment group with significant differences in average change for isometric rate of force development (p = 0.016 left leg; p = 0.028 right leg). No statistical significance was reached for other parameters. CONCLUSIONS: The findings of this study indicate that the used training protocol for long term care elderly is feasible, however, requires more closely monitoring of participants; e.g. needs protocol modifications that target improved compliance with the intervention in this setting. SR-WBV shows beneficial effects on physical performance for those adhering to the intervention. TRIAL REGISTRATION: U.S. National Institutes of Health NCT01543243. PMID- 26865871 TI - The time course of changes induced by resistance training and detraining on muscular and physical function in older adults. AB - BACKGROUND: It is generally recognised that the physical functioning of older adults is enhanced with resistance exercise. The aim of this study was to investigate the time course of changes in upper and lower body muscle strength and physical function in older individuals following a 16 week resistance training (RT) programme and a similar duration detraining (DET) period. METHODS: Forty-one inactive individuals (55 to 75 years) were randomly allocated in a RT group (n = 22; three sessions per week) and a control (CON) group (n = 19). Muscle strength was assessed with 10RM leg and bench press tests, while the Timed Up-and-Go (TUG) test was used to measure functional mobility. The Bruce treadmill test determined the participants' submaximal endurance capacity. Data were analysed using mixed model repeated measures ANOVA and P < 0.05 was considered statistically significant. RESULTS: Main treatment effects were found for muscle strength (P < 0.001) and functional mobility (P < 0.05). Upper and lower body strength generally showed a statistically significant improvement after every 4 weeks in RT (the increase after 16 weeks being 7.3 +/- 4.9 kg and 86.6 +/- 44.4 kg, respectively; P < 0.001) while TUG performance (-0.2 +/- 0.4 s; P < 0.05) and submaximal endurance capacity (0.7 +/- 0.9 min; P < 0.001) only improved after 16 weeks. Although muscle strength decreased after DET, it was still better than at baseline. No significant improvements in any performance variable were observed in CON directly after the intervention period (0-16 weeks) (P > 0.05). CONCLUSION: A 16-week RT programme has positive effects on both muscular and physical function in older adults, although the time course of these adaptations is different. While the gains in muscle strength and submaximal endurance capacity were not totally lost after DET, functional mobility was completely reversed. Older adults can be reassured that if the need arises to discontinue RT for a certain period they will still retain a large amount of their acquired muscle strength, as well as a degree of physical function such as submaximal endurance capacity. The association between leg strength and submaximal endurance capacity strengthens the notion that RT should be incorporated in training and rehabilitation programmes of ageing and frail older adults. PMID- 26865870 TI - Possible neurocognitive benefits of exercise in persons with heart failure. AB - More than 6 million Americans have heart failure (HF) and more than 500,000 are diagnosed each year. In addition to its many adverse medical consequences, HF is also a significant risk factor for neurological disorders like Alzheimer's disease and associated with cognitive impairment long prior to the onset of these conditions. Converging bodies of literature suggest cognitive dysfunction in HF may be at least partially modifiable. One key mechanism for cognitive improvement is improved cerebral blood flow, which may be possible with exercise in patients with HF. This brief review provides a model for the likely neurocognitive benefits of exercise in HF and encourages further work in this area. PMID- 26865872 TI - Health benefits of cycle ergometer training for older adults over 70: a review. AB - As the number of older adults continues to increase worldwide, more attention is being paid to geriatric health care needs, and successful ageing is becoming an important topic in the medical literature. A preventive approach to the care of older adults is thus a priority in our aging societies. The purpose of this study was to update evidence for the health benefits of cycle ergometer training for older adults over 70. We searched online electronic databases up to September 2014 for original observational and intervention studies on the relationship between cycle ergometer training and health among older patients over 70. Twenty five studies examined interventions aimed specifically at promoting cycling for older adults over 70. These studies reported a positive effect on the prevention of cardiovascular disease, and a significant improvement in metabolic responses. Improving functional status, muscle strength and cognitive performance are also well established. Overall, this review demonstrates a positive effect of cycle ergometer training with functional benefits and positive health outcomes for older adults over 70. Based on this evidence, clinicians can now encourage older adults to profit from the health benefits of cycle ergometer training to be able to pursue their daily activities independently. PMID- 26865873 TI - A comparison of linear and nonlinear stability parameters in different clinical forms of multiple sclerosis. AB - BACKGROUND: Multiple sclerosis (MS) is one of the neurological diseases that affect the ability of subjects to stand and walk. The stability of MS subjects has been evaluated in various studies, mostly based on linear approach. Based on this approach it is controversial weather stability of MS subjects differ from normal or not. Therefore, the aim of this study was to evaluate stability in three groups of MS subjects (spastic, ataxic and ataxic-spastic) using both linear and non-linear approaches. METHOD: Seventeen healthy and 36 subjects with MS participated in this study. The MS group presenting with spastic, ataxic and ataxic-spastic (each group consisted of 12 subjects) participated in the study. The stability of the subjects was evaluated using Kistler force plate. The difference between stability of the subjects was evaluated using the Multi Analysis of Variance and significant value was set at P < 0.05. RESULT: There was a significant difference in the mean value of Approximate Entropy (ApEn) in anterior-posterior direction between normal (0.66 +/- 0.13) and ataxic (0.85 +/- 0.12) and ataxic-spastic (0.90 +/- 0.12) subjects (P < 0.05) and no difference between normal and spastic groups (0.76 +/- 0.13). The results of both linear and nonlinear approaches confirmed that both ataxic and ataxic-spastic subjects had more instability than normal subjects. Although, the mean values of stability parameters increased in spastic compared to normal, the difference was not statistically significant. CONCLUSION: Subjects with ataxic and ataxic-spastic MS disorder had difficulty in controlling their stability during quiet standing. The results of this study also confirmed that spasticity of muscles surrounding the hip and knee joints did not influence standing stability in patients with spastic MS. PMID- 26865874 TI - ICT-based system to predict and prevent falls (iStoppFalls): results from an international multicenter randomized controlled trial. AB - BACKGROUND: Falls and fall-related injuries are a serious public health issue. Exercise programs can effectively reduce fall risk in older people. The iStoppFalls project developed an Information and Communication Technology-based system to deliver an unsupervised exercise program in older people's homes. The primary aims of the iStoppFalls randomized controlled trial were to assess the feasibility (exercise adherence, acceptability and safety) of the intervention program and its effectiveness on common fall risk factors. METHODS: A total of 153 community-dwelling people aged 65+ years took part in this international, multicentre, randomized controlled trial. Intervention group participants conducted the exercise program for 16 weeks, with a recommended duration of 120 min/week for balance exergames and 60 min/week for strength exercises. All intervention and control participants received educational material including advice on a healthy lifestyle and fall prevention. Assessments included physical and cognitive tests, and questionnaires for health, fear of falling, number of falls, quality of life and psychosocial outcomes. RESULTS: The median total exercise duration was 11.7 h (IQR = 22.0) over the 16-week intervention period. There were no adverse events. Physiological fall risk (Physiological Profile Assessment, PPA) reduced significantly more in the intervention group compared to the control group (F1,127 = 4.54, p = 0.035). There was a significant three-way interaction for fall risk assessed by the PPA between the high-adherence (>90 min/week; n = 18, 25.4 %), low-adherence (<90 min/week; n = 53, 74.6 %) and control group (F2,125 = 3.12, n = 75, p = 0.044). Post hoc analysis revealed a significantly larger effect in favour of the high-adherence group compared to the control group for fall risk (p = 0.031), postural sway (p = 0.046), stepping reaction time (p = 0.041), executive functioning (p = 0.044), and quality of life (p for trend = 0.052). CONCLUSIONS: The iStoppFalls exercise program reduced physiological fall risk in the study sample. Additional subgroup analyses revealed that intervention participants with better adherence also improved in postural sway, stepping reaction, and executive function. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Trial ID: ACTRN12614000096651 International Standard Randomised Controlled Trial Number: ISRCTN15932647. PMID- 26865875 TI - The effect of sensor-based exercise at home on functional performance associated with fall risk in older people - a comparison of two exergame interventions. AB - BACKGROUND: There is good evidence that balance challenging exercises can reduce falls in older people. However, older people often find it difficult to incorporate such programs in their daily life. Videogame technology has been proposed to promote enjoyable, balance-challenging exercise. As part of a larger analysis, we compared feasibility and efficacy of two exergame interventions: step-mat-training (SMT) and Microsoft-Kinect(r) (KIN) exergames. METHODS: 148 community-dwelling people, aged 65+ years participated in two exergame studies in Sydney, Australia (KIN: n = 57, SMT: n = 91). Both interventions were delivered as unsupervised exercise programs in participants' homes for 16 weeks. Assessment measures included overall physiological fall risk, muscle strength, finger-press reaction time, proprioception, vision, balance and executive functioning. RESULTS: For participants allocated to the intervention arms, the median time played each week was 17 min (IQR 32) for KIN and 48 min (IQR 94) for SMT. Compared to the control group, SMT participants improved their fall risk score (p = 0.036), proprioception (p = 0.015), reaction time (p = 0.003), sit-to-stand performance (p = 0.011) and executive functioning (p = 0.001), while KIN participants improved their muscle strength (p = 0.032) and vision (p = 0.010), and showed a trend towards improved fall risk scores (p = 0.057). CONCLUSIONS: The findings suggest that it is feasible for older people to conduct an unsupervised exercise program at home using exergames. Both interventions reduced fall risk and SMT additionally improved specific cognitive functions. However, further refinement of the systems is required to improve adherence and maximise the benefits of exergames to deliver fall prevention programs in older people's homes. TRIAL REGISTRATIONS: ACTRN12613000671763 (Step Mat Training RCT) ACTRN12614000096651 (MS Kinect RCT). PMID- 26865876 TI - Effects of whole-body vibration on proxies of muscle strength in old adults: a systematic review and meta-analysis on the role of physical capacity level. AB - BACKGROUND: Dynapenia (age-associated loss of muscle strength not caused by neurologic or muscular diseases) and functional limitations (e.g. climbing stairs, chair rising) are important problems in elderly persons. Whole body vibration, used as an adjunct to classical resistance training or even as a stand alone alternative, might help to reduce these problems. Its value might be highest in elderly persons with very low function, where whole body vibration can be used as a skilling up training until more conventional exercise types are possible. This systematic review and meta-analysis summarized the current evidence for whole-body vibration interventions on isometric maximum voluntary contraction, dynamic strength, power, rate of force development and functional strength in elderly categorised in different subgroups based on function levels. METHODS: An extensive literature search was carried out in February 2014 and repeated in February 2015 at PubMed, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database and CINAHL electronic databases. The International Clinical Trials Registry Platform from the World Health Organization was also searched. Randomized controlled trials measuring isometric maximum voluntary contraction, dynamic strength, power, rate of force development and functional strength in studies using WBV intervention in 65 years or older elderly individuals were included. The methodological quality of included studies was assessed using the Cochrane Collaboration's tool for assessing Risk of Bias. Studies were classified based on the level of physical capacitiy of the participants as "Go-Go", "Slow-Go" or "No-Go". Data were pooled using a random effects model. RESULTS: Thirty-eigth articles of moderate methodological quality were included. The vibration modes for sinusoidal vertical whole-body vibration was between 25 and 40 Hz, the amplitude varied from 2 to 4 mm. Sinusoidal side alternating -whole-body vibration revealed frequencies from 2.5 to 35 Hz with amplitudes ranging from 0.05 to 12 mm. Stochastic resonance whole-body vibration used frequencies between 3 and 6 Hz. Effect sizes in Go-Go were moderate after vertical sinusoidal Whole-body vibration compared to non-training control groups for isometric maximum voluntary contraction with effect size 0.48 (95 % CI 0.33 to 0.63) and for Dynamic Strength with effect size 0.47 (95 % CI 0.06 to 0.88). Side-alternating sinusoidal whole body vibration showed moderate effect sizes with 0.69 (95 % CI 0.32 to 1.06) for isometric maximum voluntary contraction, 0.50 (95 % CI 0.07 to 0.92) for power, 0.40 (95 % CI 0.16 to 0.64) for Rate of Force Development and 0.42 (95 % CI 0.13 to 0.71) for Functional Strength compared to non-exercise control. The analysis for Slow-Go showed for stochastic resonance whole-body vibration and Functional Strength an effect size of 0.97 (95 % CI -0.07 to 2.00) compared to non-exercise control in one study. No-Go showed for stochastic resonance whole-body vibration a moderate effect size with 0.50 (95 % CI -0.32 to 1.33) for Functional Strength compared to non-exercise control. CONCLUSIONS: Whole-body vibration shows beneficial effects, mainly in the No-Go group elderly compared to non-training control and conventional strength training groups. The results suggest that WBV can be used as a skilling-up exercise in participants not able to perform standard exercises. Further studies with the various types of WBV in various sub-populations of elderly persons are needed to determine the most effective vibration modes. TRIAL REGISTRATION: REGISTRATION NUMBER: CRD42013006489. PMID- 26865877 TI - The design of a purpose-built exergame for fall prediction and prevention for older people. AB - BACKGROUND: Falls in older people represent a major age-related health challenge facing our society. Novel methods for delivery of falls prevention programs are required to increase effectiveness and adherence to these programs while containing costs. The primary aim of the Information and Communications Technology-based System to Predict and Prevent Falls (iStoppFalls) project was to develop innovative home-based technologies for continuous monitoring and exercise based prevention of falls in community-dwelling older people. The aim of this paper is to describe the components of the iStoppFalls system. METHODS: The system comprised of 1) a TV, 2) a PC, 3) the Microsoft Kinect, 4) a wearable sensor and 5) an assessment and training software as the main components. RESULTS: The iStoppFalls system implements existing technologies to deliver a tailored home-based exercise and education program aimed at reducing fall risk in older people. A risk assessment tool was designed to identify fall risk factors. The content and progression rules of the iStoppFalls exergames were developed from evidence-based fall prevention interventions targeting muscle strength and balance in older people. CONCLUSIONS: The iStoppFalls fall prevention program, used in conjunction with the multifactorial fall risk assessment tool, aims to provide a comprehensive and individualised, yet novel fall risk assessment and prevention program that is feasible for widespread use to prevent falls and fall related injuries. This work provides a new approach to engage older people in home-based exercise programs to complement or provide a potentially motivational alternative to traditional exercise to reduce the risk of falling. PMID- 26865878 TI - Aerobic training as a means to enhance inhibition: what's yet to be studied? AB - Some of the neurodegenerative processes in healthy aging, including changes in structural and biochemical properties of the brain, are argued to affect cortical inhibitory functions. Age-related deficits in the ability to control cerebral inhibition may explain wide range of motor and cognitive deficits that healthy older adults experience in daily life such as impaired coordination skills and declines in attention, concentration, and learning abilities. Importantly, evidence from many studies suggests that impaired inhibitory control in advancing age can be delayed or even alleviated by aerobic exercise training. Findings from a recent study by Duchesne and colleagues (2015) may provide insights into this process. First, observations from Duchesne et al. indicated that aerobic exercise training program improved cognitive inhibitory functioning in both patients with Parkinson's disease (PD) and matched older controls. Second, Duchesne et al. showed that cognitive inhibition and motor skills were highly correlated both pre and post-exercise in PD but not in controls. Based on the aforementioned findings we highlight possible mechanisms that may play a role in the interactions between cognitive and motor inhibitory functions in healthy elderly that could benefit from aerobic exercise training: specifically, the brain neurotransmission systems and the frontal-basal ganglia network. In conclusion, we raise two fundamental questions which are yet to be addressed: (1) the extent to which different brain neurotransmitter systems are affected by aerobic exercise training; (2) the extent to which neurotransmitter levels prior to the onset of intervention may facilitate (or impede) training-induced neuroplasticity in the aging brain. PMID- 26865879 TI - Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study. AB - BACKGROUND: The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control of a specific gene. The aim of the present study was to examine the effect of the interaction between physical activity and BDNF Val66Met (rs6265), a genetic polymorphism, on episodic memory. METHODS: Two hundred and five volunteers aged 55 and older with a Mini Mental State Examination score >= 24 participated in this study. Four groups of participants were established according to their physical activity level and polymorphism BDNF profile (Active Val homozygous, Inactive Val homozygous, Active Met carriers, Inactive Met carriers). Episodic memory was evaluated based on the delayed recall of the Logical Memory test of the MEM III battery. RESULTS: As expected, the physical activity level interacted with BDNF polymorphism to affect episodic memory performance (p < .05). The active Val homozygous participants significantly outperformed the active Met carriers and inactive Val homozygous participants. CONCLUSION: This study clearly demonstrates an interaction between physical activity and BDNF Val66Met polymorphism that affects episodic memory in the elderly and confirms that physical activity contributes to the neurotrophic mechanism implicated in cognitive health. The interaction shows that only participants with Val/Val polymorphism benefited from physical activity. PMID- 26865880 TI - Physical activity and neurocognitive functioning in aging - a condensed updated review. AB - This condensed review gives an overview about two methodological approaches to study the impact of physical activity on cognition in elderly, namely cross sectional studies and randomized controlled intervention studies with pre- and post-measures. Moreover, this review includes studies investigating different types of physical activity and their relation to cognitive functions in older age. Behavioral data are considered but the main focus lies on neuroscientific methods like event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI). PMID- 26865881 TI - Kinect-based choice reaching and stepping reaction time tests for clinical and in home assessment of fall risk in older people: a prospective study. AB - BACKGROUND: Quick protective reactions such as reaching or stepping are important to avoid a fall or minimize injuries. We developed Kinect-based choice reaching and stepping reaction time tests (Kinect-based CRTs) and evaluated their ability to differentiate between older fallers and non-fallers and the feasibility of administering them at home. METHODS: A total of 94 community-dwelling older people were assessed on the Kinect-based CRTs in the laboratory and were followed up for falls for 6 months. Additionally, a subgroup (n = 20) conducted the Kinect based CRTs at home. Signal processing algorithms were developed to extract features for reaction, movement and the total time from the Kinect skeleton data. RESULTS: Nineteen participants (20.2 %) reported a fall in the 6 months following the assessment. The reaction time (fallers: 797 +/- 136 ms, non-fallers: 714 +/- 89 ms), movement time (fallers: 392 +/- 50 ms, non-fallers: 358 +/- 51 ms) and total time (fallers: 1189 +/- 170 ms, non-fallers: 1072 +/- 109 ms) of the reaching reaction time test differentiated well between the fallers and non fallers. The stepping reaction time test did not significantly discriminate between the two groups in the prospective study. The correlations between the laboratory and in-home assessments were 0.689 for the reaching reaction time and 0.860 for stepping reaction time. CONCLUSION: The study findings indicate that the Kinect-based CRT tests are feasible to administer in clinical and in-home settings, and thus represents an important step towards the development of sensor based fall risk self-assessments. With further validation, the assessments may prove useful as a fall risk screen and home-based assessment measures for monitoring changes over time and effects of fall prevention interventions. PMID- 26865882 TI - Maximizing Data Quality using Mode Switching in Mixed-Device Survey Design: Nonresponse Bias and Models of Demographic Behavior. AB - Conducting survey interviews on the internet has become an attractive method for lowering data collection costs and increasing the frequency of interviewing, especially in longitudinal studies. However, the advantages of the web mode for studies with frequent re-interviews can be offset by the serious disadvantage of low response rates and the potential for nonresponse bias to mislead investigators. Important life events, such as changes in employment status, relationship changes, or moving can cause attrition from longitudinal studies, producing the possibility of attrition bias. The potential extent of such bias in longitudinal web surveys is not well understood. We use data from the Relationship Dynamics and Social Life (RDSL) study to examine the potential for a mixed-device approach with active mode switching to reduce attrition bias. The RDSL design allows panel members to switch modes by integrating telephone interviewing into a longitudinal web survey with the objective of collecting weekly reports. We found that in this design allowing panel members to switch modes kept more participants in the study compared to a web only approach. The characteristics of persons who ever switched modes are different than those who did not - including not only demographic characteristics, but also baseline characteristics related to pregnancy and time-varying characteristics that were collected after the baseline interview. This was true in multivariate models that control for multiple of these dimensions simultaneously. We conclude that mode options and mode switching is important for the success of longitudinal web surveys to maximize participation and minimize attrition. PMID- 26865884 TI - Prevalence of Work-Related Asthma in Primary Health Care: Study Rationale and Design. AB - BACKGROUND: Occupational Asthma (OA) is the most frequent origin of occupational respiratory diseases in industrialized countries and accounts for between 5% and 25% of asthmatic patients. The correct and early diagnosis of OA is of great preventive and socio-economic importance. However, few studies exist on OA's prevalence in Catalonia and in Spain and those affected are mainly treated by the public health services and not by the occupational health services, which are private. OBJECTIVE: To determine the prevalence of OA in patients diagnosed with asthma in the Primary Healthcare system and to evaluate the socio-economic impact of OA in the Primary Healthcare system. METHODS/DESIGN: We will carry out an observational, transversal and multi-center study in the Primary Healthcare Service in the Barcelona region (Catalonia, Spain), with 385 asthmatic workers aged between 16 and 64 who are currently working or have been working in the past. We will confirm the asthma diagnosis in each patient, and those meeting the inclusion criteria will be asked to answer a questionnaire that aims to link asthma to the patient's past employment history. The resulting diagnosis will be of either occupational asthma, work-aggravated asthma or common asthma. We will also collect socio-demographic information about the patients, about their smoking status, their exposure outside of the workplace, their work situation at the onset of the symptoms, their employment history, their symptoms of asthma, their present and past medical asthma treatment, and, in order to estimate the economic impact in the Primary Healthcare system, where they have been attended to and treated. Prevalence will link OA or work-aggravated asthma to the total of patients participating in the study with a asthma diagnosis. DISCUSSION: The results will show the prevalence of OA and work-aggravated asthma, and shall provide valuable information to set out and apply the necessary personal and technical measures, either in the public or in the occupational health services. No studies evaluating the costs generated by the OA in the Primary Healthcare system have been carried out. PMID- 26865885 TI - Anaesthesia for minimally invasive surgery. AB - Minimally invasive surgery (MIS) is rising in popularity. It offers well-known benefits to the patient. However, restricted access to the surgical site and gas insufflation into the body cavities may result in severe complications. From the anaesthetic point of view MIS poses unique challenges associated with creation of pneumoperitoneum, carbon dioxide absorption, specific positioning and monitoring a patient to whom the anaesthetist has often restricted access, in a poorly lit environment. Moreover, with refinement of surgical procedures and growing experience the anaesthetist is presented with patients from high-risk groups (obese, elderly, with advanced cardiac and respiratory disease) who once were deemed unsuitable for the laparoscopic technique. Anaesthetic management is aimed at getting the patient safely through the procedure, minimizing the specific risks arising from laparoscopy and the patient's coexisting medical problems, ensuring quick recovery and a relatively pain-free postoperative course with early return to normal function. PMID- 26865886 TI - Results of endoscopic and surgical fistula treatment in oesophagointestinal anastomosis after gastrectomy. AB - INTRODUCTION: Intestinal fistulas occur in 4-8% of cases of upper gastrointestinal tract surgery. Until now, surgery has been the standard of treating fistulas in oesophagointestinal anastomosis. The use of stents and haemoclips still causes much controversy, but more and more publications present good results with this type of treatment. AIM: To present results of endoscopic and surgical treatment of fistulas in oesophagointestinal anastomosis after gastrectomy. MATERIAL AND METHODS: A fistula in the oesophagointestinal anastomosis was observed in 23 (4.8%) patients within an 18-year period. The indications for endoscopic treatment were small fistulas (< 50 ml/day), and large (> 50 ml/day) fistulas in subjects with no symptoms of peritonitis or abscess were treated with implantation a of covered stent. Surgical treatment was performed with a large fistula leading to peritonitis and complicated gangrene of margins and/or the presence of abscess. RESULTS: Four subjects were treated endoscopically with the use of haemoclips, resulting in 50% technical and clinical success. We implanted stents in 12 patients. Technical success was achieved in all the patients, yet permanent closure of the fistula was reported for 8 (66%) subjects. The percentage of patients operated on for fistula was 33%. We recorded 4 deaths in this group. CONCLUSIONS: The use of haemoclips in treatment of small fistulas, and self-expandable, covered stents in treatment of medium and large fistulas, is an effective method that shortens the hospitalisation period and accelerates introduction of oral nutrition while reducing the number of fatal complications. PMID- 26865887 TI - Impact of post-laparoscopic sleeve gastrectomy weight loss on C-reactive protein, lipid profile and CA-125 in morbidly obese women. AB - INTRODUCTION: Obesity increases production of adipose tissue-derived proteins, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Also there are elevated levels of C-reactive protein (CRP) and IL-6, CD8, and CD4, indicating chronic subclinical inflammation. Since obesity represents a serious risk factor in several metabolic diseases, identifying the status of carbohydrate antigen-125 (CA-125) would further link obesity and tumors. AIM: To examine the effect of weight loss by laparoscopic sleeve gastrectomy (LSG) on plasma CRP, lipid profiles and CA-125 level in morbidly obese patients. MATERIAL AND METHODS: This prospective study was conducted in the Surgery Department, Fayoum University Hospital, between August 2013 and September 2015. To assess the effect of excess weight loss following this operation CRP, lipid profile and CA-125 were measured before and 12 months after the LSG operation for weight loss. The study included 30 cases of morbidly obese patients: 30 (100%) females aged 23-55 years who were considered clinically obese with a mean body mass index of 42.71 +/-4.3 (38-46) kg/m(2) and mean age of 40.3 +/-8.5 (23-55) years. The National Institute of Health (NIH) inclusion criteria for bariatric surgery were used. RESULTS: A mean weight loss of 29.30% decreased plasma CRP, triglycerides, total cholesterol and low-density lipoprotein cholesterol (HDL cholesterol), CA-125 level and increased high-density lipoprotein cholesterol (HDL cholesterol) The percentage weight loss was significantly associated with changes in plasma CRP, triglycerides, total cholesterol, total HDL cholesterol and CA-125. CONCLUSIONS: Weight loss by LSG improves inflammation, dyslipidemia and CA-125 level. PMID- 26865888 TI - Transpapillary drainage of walled-off pancreatic necrosis - a single center experience. AB - INTRODUCTION: Walled-off pancreatic necrosis (WOPN) often coexists with disruption of the main pancreatic duct that manifests as a leak of contrast medium into the necrotic collection during endoscopic retrograde pancreatography. AIM: To assess the efficacy and safety of treatment of patients with symptomatic WOPN and disruption of the main pancreatic duct, who underwent endoscopic transpapillary drainage as the only access to the necrosis cavity. MATERIAL AND METHODS: In 22 patients with symptomatic WOPN, active endoscopic transpapillary drainage was performed. During endoscopic retrograde pancreatography (ERP), partial disruption of the main pancreatic duct was observed in 14 patients and complete disruption in 8 patients. After the active drainage was finished, a transpapillary pancreatic stent was inserted into the main pancreatic duct, which was later exchanged after 6, 12 and 24 months or when no extravasation of contrast from the pancreatic duct was observed. The results of treatment and complications were compared retrospectively. RESULTS: The mean duration of active drainage was 22 (range: 7-94) days. Complications of endotherapy occurred in 3/22 patients. The mean time of the main pancreatic duct stenting was 304 (range: 85 519) days. Success of endoscopic treatment of WOPN and pancreatic duct disruption was achieved in 20/22 patients. During a 1-year follow-up, recurrence of the collection was noted in 4/20 patients. Long-term success was achieved in 16/22 patients. CONCLUSIONS: In patients with WOPN who cannot undergo transmural drainage when there is a communication between the necrotic collection and the main pancreatic duct, transpapillary access may be an effective and safe method of treatment. PMID- 26865889 TI - Hybrid technique for postoperative ventral hernias - own experience. AB - INTRODUCTION: There are many techniques which may be involved in abdominal hernia repair, from classical to tension-free. Treatment of complicated hernias has undergone evolution. Many surgeons consider the laparoscopic method as a method of choice for incisional hernia repair. Sometimes miniinvasive repair of complicated hernia is not so easy to perform. We are convinced that selected patients may benefit from combined open and laparoscopic techniques. AIM: To present the operating technique and early results of treatment of 15 patients operated on using the 3 hybrid technique. MATERIAL AND METHODS: Fifteen patients suffering from recurrent incisional hernias underwent the hybrid technique for their repair between June 2012 and April 2015. The hybrid technique was performed using synthetic meshes in 14 cases and a biological implant in 1 case. RESULTS: The early postoperative period was uncomplicated in all cases. Within a maximum follow-up period of 32 months, two deep wound infections were observed. CONCLUSIONS: The hybrid technique may be used in patients with recurrent incisional hernias. PMID- 26865890 TI - In search of the ideal patient for the intragastric balloon - short- and long term results in 70 obese patients. AB - INTRODUCTION: Treating concomitant diseases in obese patients generates costs which are twice as high as the costs of the therapies in individuals with a normal weight. The conservative management of obesity involving lifestyle and dietary modifications and medical treatment shows only short-term efficacy and carries a 90% risk of recurrence. The intragastric balloon causes a permanent feeling of satiety, thus reducing the amount of food consumed by the patient. AIM: To assess the early and long-term effect of intragastric balloon treatment in obese patients. MATERIAL AND METHODS: In 2012, we performed 75 intragastric balloon procedures in obese patients. A total of 70 patients were enrolled in the study. The balloon was removed at 6 months. The patients were interviewed 2 years after removal. RESULTS: Upon balloon removal, mean total weight loss (TWL) was 15.9 kg, and excess weight loss (EWL) was 41 +/-19.6% (p < 0.001). Only one patient was classified as a non-respondent. Satisfactory results (> 10% TWL) were achieved in all other patients. The mean body mass index (BMI) reduction was 5.8 kg/m(2) (15.5%) (p < 0.001). Two years later 45 patients still maintained reduced weight, 7 returned to baseline body weight, whereas 18 subjects experienced a full yo-yo effect (mean gain of 2.7 kg). During 2 years following the balloon removal, mean total weight increased by 10.9 kg, and mean BMI increased by 3.9 kg/m(2) (12.5%). A satisfactory effect (> 10% TWL) was achieved in only 19 patients. CONCLUSIONS: Obesity management with the intragastric balloon is a safe treatment method, which effectively induces weight loss. Poor tolerance and lack of response occurring in some individuals should be taken into consideration. The best results are achieved in women with class 1 obesity. PMID- 26865892 TI - Three-dimensional intraoperative imaging with O-arm to establish a working trajectory in percutaneous endoscopic lumbar discectomy. AB - INTRODUCTION: Successful percutaneous endoscopic lumbar discectomy (PELD) requires an appropriate working trajectory. Due to the complexity of spinal anatomy, this is difficult to verify with conventional 2-dimensional fluoroscopy. AIM: Here we assessed the feasibility and utility of the O-arm for establishing the working trajectory for PELD. MATERIAL AND METHODS: We retrospectively reviewed the records of 89 patients with lumbar disc herniation who underwent PELD using the O-arm. The working trajectory was evaluated with standard fluoroscopic images or 3-dimensional, volumetric computed tomography scan. Based on the detail provided by the multiplanar view, we confirmed the ideal working trajectory and adjusted the surgical approach accordingly. RESULTS: At the 12 month follow-up, based on MacNab's criteria, 85.9% of patients showed an excellent or good outcome. There were no major complications. CONCLUSIONS: The O arm provides detailed multiplanar intraoperative high-quality imaging for PELD, and enables the surgeon to ascertain the surgical anatomy, determine the optimal working trajectory, and improve the accuracy of surgery. PMID- 26865891 TI - Minimally invasive direct coronary artery bypass for left anterior descending artery revascularization - analysis of 300 cases. AB - INTRODUCTION: Minimally invasive direct coronary artery bypass (MIDCAB) grafting is performed via small, left anterolateral thoracotomy. The left internal mammary artery was grafted to the left anterior descending (LAD) artery in 300 consecutive patients. AIM: In-hospital results were evaluated and compared with the conventional, off-pump coronary artery bypass graft procedure. MATERIAL AND METHODS: One hundred and sixty-three (54.33%) of 300 patients underwent staged hybrid coronary revascularization, 93 (31%) were treated for a single LAD lesion, and 44 (14.67%) were treated for multi-vessel disease with reasonably incomplete revascularization. Major in-hospital cardiac adverse events and postoperative data were compared between groups. RESULTS: Preoperative data were similar between groups. However, the difference in left ventricular ejection fraction (p < 0.001) was significant. No conversions to sternotomy occurred during the primary MIDCAB procedures. Shorter operation time (p < 0.001), shorter postoperative mechanical ventilation time (p < 0.001), shorter intensive care unit stay (p < 0.001), and less red blood cell transfusion (p < 0.001) were noted in the MIDCAB group. Postoperative coronary angiography conducted in the MIDCAB group within one week after the operation showed that 2 of 163 patients developed graft occlusion. These patients underwent conventional CABG and recovered well. No significant differences were observed in postoperative MI, delayed wound healing or 30-day in-hospital mortality between the two groups. CONCLUSIONS: The use of a chest wall lifting system and modified stabilizer makes the MIDCAB procedure safer and easier. The MIDCAB procedure is demonstrated to be a feasible and minimally invasive alternative for patients with coronary artery disease involving LAD lesions. PMID- 26865893 TI - Removal of uterine fibroids by mini-laparotomy technique in women who wish to preserve their uterus and fertility. AB - INTRODUCTION: The minilaparotomy is considered to be a safe and effective alternative to laparoscopy and abdominal laparotomy in myomectomy cases. AIM: To perform a retrospective analysis of pre-surgical assessment, surgical course and post-operational parameters in women wishing to preserve their uterus and fertility who underwent myomectomy by minilaparotomy in the Department of Gynecology and Gynecological Oncology at the Polish Mother's Memorial Hospital - Research Institute in Lodz in the years 2008-2014. MATERIAL AND METHODS: A total of 76 patients were qualified for minilaparotomy due to a benign gynecological pathology. Only 21 patients with uterine fibroids who wanted to preserve their uterus and fertility were appropriate for this study. Patients' records were analyzed in terms of: epidemiological history, surgical course, postoperative stay and pathological data. All studied patients were asked in 2014 about conception and pregnancy after minilaparotomy. RESULTS: The median age was 35.7 years. The median patient body mass index (BMI) was 24 kg/m(2). The average decrease of hemoglobin was 1.5 g/dl. The size of the myoma was between 1.5 and 15 cm. There were no serious post-surgical complications. The size of the myoma did not correlate significantly with operation time, BMI or blood loss. There was no statistically significant dependence between operation time and average hematocrit and hemoglobin decrease. In our group 7 patients who had undergone myomectomy tried to achieve conception. Four of them succeeded in pregnancy and gave birth to healthy infants. CONCLUSIONS: Myomectomy performed via minilaparotomy is a safe procedure for patients willing to preserve their uterus and fertility, and it combines some advantages of both laparotomy and laparoscopy. PMID- 26865894 TI - C-reactive protein and procalcitonin predict anastomotic leaks following colorectal cancer resections - a prospective study. AB - INTRODUCTION: Early safe discharge is paramount for the success of ERAS following colorectal cancer resections. Anastomotic leakage (AL) has high morbidity, particularly if the patient has been discharged to the community. AIM: To evaluate whether C-reactive protein (CRP) and procalcitonin (PCT) can predict AL before early discharge. MATERIAL AND METHODS: Fifty-five consecutive patients undergoing open and robotic colorectal cancer resections were included. C reactive protein and PCT were measured pre-operatively, 8 h after incision, and on the first and third postoperative day. Thirty-day readmissions, re-operations and mortality were recorded. RESULTS: Twenty-nine patients underwent robotic and the remainder open (n = 26) resections. Five patients had AL. The mean CRP and PCT increased on postoperative day 1 (POD 1) and POD 3 in all patients. On POD 3, mean CRP was 114 mg/l in non-AL patients and 321 mg/l in AL patients (p = 0.0001). Mean PCT on POD 3 was 0.56 ng/ml in the non-AL group and 10.4 ng/ml in AL patients (p = 0.017). On analysis of ROC and AUC curves, the cut-off for CRP on POD 3 was 245.64 mg/l, with 100% sensitivity and 98% specificity for AL. The cut-off for PCT on POD 3 was 3.83 ng/ml, with 75% sensitivity and 100% specificity for AL. CONCLUSIONS: C-reactive protein and PCT measurement on POD 3 following colorectal cancer resection can positively identify patients at low risk of anastomotic leakage. PMID- 26865895 TI - Successful laparoscopic management of a rare complication after embryo transfer: ovarian pregnancy. A case report and up-to-date literature review. AB - Ovarian pregnancy (OP) after embryo transfer is very rare. Due to the rarity and the asymptomatic nature, there are still difficulties in diagnosis and treatment. The traditional operative treatment for OP has been oophorectomy. However, the desire to maintain reproductive capability and improvements in laparoscopy have more recently led to conservative laparoscopic techniques. This rare complication could be diagnosed early and managed by a conservative laparoscopic approach. Here we present a survey of the literature and a case of successful laparoscopic management of ovarian pregnancy after intracytoplasmic sperm injection and embryo transfer. The current case is the first case in the literature in which ovarian pregnancy occurred after a single embryo transfer. We also summarize the literature about management of ovarian pregnancy after embryo transfer. PMID- 26865896 TI - Removal of gallstone from mesorectum after laparoscopic cholecystectomy - new indication for transanal endoscopic microsurgery technique. AB - Transanal endoscopic microsurgery (TEM) is a minimally invasive technique for local excision of benign and malignant neoplasms in the rectum. Indications for this technique are constantly changing and extending. The aim of this study is to describe a case of a unique and innovative application of this surgical technique. A 72-year-old patient was admitted to the Clinical Department of General and Colorectal Surgery for elective resection of a tumor located in the perianal area using the TEM surgical technique. In August 2005 the patient underwent laparoscopic cholecystectomy due to symptomatic cholecystitis. From March 2011 the patient complained about ongoing sharp pain in the perianal and presacral area. Computed tomography revealed two oval areas approximately 30 mm in size to the right of the sigmoido-rectal region communicating with the colon lumen. Subsequently diverticulitis was diagnosed. The TEM technique was uniquely used to successfully remove the gallstone from the 72-year-old patient's presacral area. PMID- 26865897 TI - Laparoscopic approach in the treatment of large epiphrenic esophageal diverticulum. AB - Epiphrenic diverticulum of the lower third of the esophagus is a relatively rare disorder. We present the case of a large, 7.5 cm diameter esophageal epiphrenic diverticulum treated by the laparoscopic approach. Surgery was indicated by the severity of the patient's symptoms and size of the diverticulum. A laparoscopic transhiatal diverticulectomy with a myotomy and Dor fundoplication was carried out. The overall operative time was 180 min. The patient tolerated the surgery well and was discharged from hospital 4 days after the surgery. From the 10(th) postoperative day the patient resumed a regular diet. Four weeks after the operation the patient had no complaints, symptoms of dysphagia or vomiting. The laparoscopic approach in the treatment of a large, 7.5 cm epiphrenic diverticulum of the esophagus is feasible, safe and well tolerated by the patient. PMID- 26865898 TI - Is it appropriate to perform anterior segment reconstruction in amblyopic eye following penetrating trauma in childhood? AB - We present a case of diagnostic and surgical management in an amblyopic eye following penetrating trauma in childhood. The 75-year-old female patient experienced the trauma at the age of 4. The eye was amblyopic, but after thorough investigations (ultrasonography, ultrabiomicroscopy, visual evoked potentials) the eye underwent anterior segment reconstruction. Visual evoked potentials allowed us to assess optic nerve function, while ultrabiomicroscopy allowed us to plan the surgical procedure. Although we observed quite a small visual acuity improvement, the subjective improvement reported by the patient was fairly significant (NEI VFQ-25 questionnaire). The cosmetic effect of the black pupil was also important. PMID- 26865899 TI - Spontaneous cerebrospinal fluid leak at the clivus. AB - We present a case report of a 60-year-old woman with a spontaneous cerebrospinal fluid leak at the clivus, obesity and no history of trauma. Follow-up imaging scans confirmed enlargement of the defect within the posterior clival framework to the size of 16 * 9 * 4 mm with a suspected meningocerebral hernia. The surgeons used the "two nostrils - four hands" endoscopic operating technique. The patient reported a history of cerebrospinal fluid leaks lasting for 3 years, with increasingly shorter leak-free periods and an increasing incidence of inflammatory complications. The patient recovered without complications, and she was discharged 14 days after the surgery. Good local outcome and improved patient condition were achieved postoperatively. PMID- 26865901 TI - In-situ photopolymerization of monodisperse and discoid oxidized methacrylated alginate microgels in a microfluidic channel. AB - We present a simple microfluidic technique to in-situ photopolymerize (by 365 nm ultraviolet) monodisperse oxidized methacrylated alginate (OMA) microgels using a photoinitiator (VA-086). By this technique, we generated monodisperse spherical OMA beads and discoid non-spherical beads with better shape consistency than ionic crosslinking methods do. We found that a high monomer concentration (8 w/v %), a high photoinitiator concentration (1.5 w/v %), and absence of oxygen are critical factors to cure OMA microgels. This photopolymerizing method is an alternative to current methods to form alginate microgels and is a simpler approach to generate non-spherical alginate microgels. PMID- 26865900 TI - Food Insecurity and Obesity Among American Indians and Alaska Natives and Whites in California. AB - Food insecurity is linked to obesity among some, but not all, racial and ethnic populations. We examined the prevalence of food insecurity and the association between food insecurity and obesity among American Indians (AIs) and Alaska Natives (ANs) and a comparison group of whites. Using the 2009 California Health Interview Survey, we analyzed responses from 592 AIs/ANs and 7371 white adults with household incomes at or below 200% of the federal poverty level. Food insecurity was measured using a standard 6-item scale. Sociodemographics, exercise, and obesity were all obtained using self-reported survey data. Logistic regression was used to estimate associations. The prevalence of food insecurity was similar among AIs/ANs and whites (38.7% vs 39.3%). Food insecurity was not associated with obesity in either group in analyses adjusted for sociodemographics and exercise. The ability to afford high-quality foods is extremely limited for low-income Californians regardless of race. Health policy discussions must include increased attention on healthy food access among the poor, including AIs/ANs, for whom little data exist. PMID- 26865902 TI - Lab-on-a-chip workshop activities for secondary school students. AB - The ability to engage and inspire younger generations in novel areas of science is important for bringing new researchers into a burgeoning field, such as lab-on a-chip. We recently held a lab-on-a-chip workshop for secondary school students, for which we developed a number of hands-on activities that explained various aspects of microfluidic technology, including fabrication (milling and moulding of microfluidic devices, and wax printing of microfluidic paper-based analytical devices, so-called MUPADs), flow regimes (gradient formation via diffusive mixing), and applications (tissue analysis and MUPADs). Questionnaires completed by the students indicated that they found the workshop both interesting and informative, with all activities proving successful, while providing feedback that could be incorporated into later iterations of the event. PMID- 26865905 TI - An integrated acoustic and dielectrophoretic particle manipulation in a microfluidic device for particle wash and separation fabricated by mechanical machining. AB - In this study, acoustophoresis and dielectrophoresis are utilized in an integrated manner to combine the two different operations on a single polydimethylsiloxane (PDMS) chip in sequential manner, namely, particle wash (buffer exchange) and particle separation. In the washing step, particles are washed with buffer solution with low conductivity for dielectrophoretic based separation to avoid the adverse effects of Joule heating. Acoustic waves generated by piezoelectric material are utilized for washing, which creates standing waves along the whole width of the channel. Coupled electro-mechanical acoustic 3D multi-physics analysis showed that the position and orientation of the piezoelectric actuators are critical for successful operation. A unique mold is designed for the precise alignment of the piezoelectric materials and 3D side wall electrodes for a highly reproducible fabrication. To achieve the throughput matching of acoustophoresis and dielectrophoresis in the integration, 3D side wall electrodes are used. The integrated device is fabricated by PDMS molding. The mold of the integrated device is fabricated using high-precision mechanical machining. With a unique mold design, the placements of the two piezoelectric materials and the 3D sidewall electrodes are accomplished during the molding process. It is shown that the proposed device can handle the wash and dielectrophoretic separation successfully. PMID- 26865904 TI - Screening applications in drug discovery based on microfluidic technology. AB - Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID- 26865906 TI - A bead-based fluorescence immunosensing technique enabled by the integration of Forster resonance energy transfer and optoelectrokinetic concentration. AB - Bead-based immunosensing has been growing as a promising technology in the point of-care diagnostics due to great flexibility. For dilute samples, functionalized particles can be used to collect dispersed analytes and act as carriers for particle manipulation. To realize rapid and visual immunosensing, Forster resonance energy transfer (FRET) was used herein to ensure only the diabetic biomarker, lipocalin 1, to be detected. The measurement was made in an aqueous droplet sandwiched between two parallel plate electrodes. With an electric field and a focused laser beam applying on the microchip simultaneously, the immunocomplexes in the droplet were further concentrated to enhance the FRET fluorescent signal. The optoelectrokinetic technique, termed rapid electrokinetic patterning (REP), has been proven to be excellent in dynamic and programmable particle manipulation. Therefore, the detection can be complete within several tens of seconds. The lower detection limit of the REP-enabled bead-based diagnosis reached nearly 5 nM. The combinative use of FRET and the optoelectrokinetic technique for the bead-based immunosensing enables a rapid measure to diagnose early stage diseases and dilute analytes. PMID- 26865903 TI - In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications. AB - Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes. PMID- 26865907 TI - Ex vivo characterization of age-associated impedance changes of single vascular endothelial cells using micro electrical impedance spectroscopy with a cell trap. AB - We aimed to characterize aging of single vascular endothelial cells, which are indicators of senescence, using micro electrical impedance spectroscopy (MUEIS) for the first time. The proposed MUEIS was equipped with two barriers under the membrane actuator near the sensing electrodes, increasing its cell-trapping capability and minimizing the interference between the target cell and subsequent cells. The cell-trapping capability in MUEIS with barriers was considerably improved (90%) with a capture time of 5 s or less, compared to MUEIS without barriers (30%). Cells were extracted from transgenic zebrafish to minimize an initial discrepancy originating from genetic differences. In order to estimate useful parameters, cytoplasm resistance and membrane capacitance were estimated by fitting an electrical equivalent circuit to the data of ex vivo sensor output. The estimated cytoplasm resistance and membrane capacitance in the younger vascular endothelial cells were 20.16 +/- 0.79 kOmega and 17.46 +/- 0.76 pF, respectively, whereas those in the older cells were 17.81 +/- 0.98 kOmega and 20.08 +/- 1.38 pF, respectively. Discrimination of each group with different aging showed statistical significance in terms of cytoplasm resistance (p < 0.001) and membrane capacitance (p < 0.001). Considering both of the sensor and cellular level, the optimal frequency was determined as 1 MHz at which the electrical impedance of each group was clearly discriminated (p < 0.001). PMID- 26865908 TI - A microfluidic electrochemical biosensor based on multiwall carbon nanotube/ferrocene for genomic DNA detection of Mycobacterium tuberculosis in clinical isolates. AB - Herein we present a microfluidic-multiplexed platform that integrates electrochemical sensors based on carbon nanotubes associated with ferrocene as redox marker (carbon nanotube (CNT)/ferrocene) for direct detection of pathogenic viral DNA from Hepatitis C and genomic DNA from Mycobacterium tuberculosis in clinical isolates. By operating the fluidic device under high flow (150 MUl/min), the formation of a very thin depletion layer at the sensor surface (deltaS = 230 nm) enhances the capture rate up to one DNA strand per second. By comparison, this capture rate is only 0.02 molecule/s in a static regime without flow. This fluidic protocol allows thus enhancing the limit of detection of the electrochemical biosensor from picomolar in bulk solution to femtomolar with a large dynamic range from 0.1 fM to 1 pM. Kinetics analysis also demonstrates an enhancement of the rate constant of electron transfer (kS) of the electrochemical process from 1 s(-1) up to 6 s(-1) thanks to the geometry of the miniaturized fluidic electrochemical cell. This microfluidic device working under high flow allows selective direct detection of a Mycobacterium tuberculosis (H37Rv) rpoB allele from clinical isolate extracted DNA. We envision that a microfluidic approach under high flow associated with a multiwall CNT/ferrocene sensor could find useful applications as the point-of-care for multi-target diagnostics of biomarkers in real samples. PMID- 26865909 TI - Genome sequence of Shinella sp. strain DD12, isolated from homogenized guts of starved Daphnia magna. AB - Shinella sp. strain DD12, a novel phosphite assimilating bacterium, has been isolated from homogenized guts of 4 days starved zooplankton Daphnia magna. Here we report the draft genome of this bacterium, which comprises 7,677,812 bp and 7505 predicted protein-coding genes. PMID- 26865910 TI - Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway. AB - BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti cancer properties. The detailed mechanisms by which oligonol may act as an anti aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways. PMID- 26865912 TI - Protective effect of dietary chitosan on cadmium accumulation in rats. AB - BACKGROUND/OBJECTIVES: Cadmium is a toxic metal that is an occupational and environmental concern especially because of its human carcinogenicity; it induces serious adverse effects in various organs and tissues. Even low levels of exposure to cadmium could be harmful owing to its extremely long half-life in the body. Cadmium intoxication may be prevented by the consumption of dietary components that potentially reduce its accumulation in the body. Dietary chitosan is a polysaccharide derived from animal sources; it has been known for its ability to bind to divalent cations including cadmium, in addition to other beneficial effects including hypocholesterolemic and anticancer effects. Therefore, we aimed to investigate the role of dietary chitosan in reducing cadmium accumulation using an in vivo system. MATERIALS/METHODS: Cadmium was administered orally at 2 mg (three times per week) to three groups of Sprague Dawley rats: control, low-dose, and high-dose (0, 3, and 5%, respectively) chitosan diet groups for eight weeks. Cadmium accumulation, as well as tissue functional and histological changes, was determined. RESULTS: Compared to the control group, rats fed the chitosan diet showed significantly lower levels of cadmium in blood and tissues including the kidneys, liver, and femur. Biochemical analysis of liver function including the determination of aspartate aminotransferase and total bilirubin levels showed that dietary chitosan reduced hepatic tissue damage caused by cadmium intoxication and prevented the associated bone disorder. CONCLUSIONS: These results suggest that dietary chitosan has the potential to reduce cadmium accumulation in the body as well as protect liver function and bone health against cadmium intoxication. PMID- 26865911 TI - D-Xylose as a sugar complement regulates blood glucose levels by suppressing phosphoenolpyruvate carboxylase (PEPCK) in streptozotocin-nicotinamide-induced diabetic rats and by enhancing glucose uptake in vitro. AB - BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. D-Xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti diabetic effects of D-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with D-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with D-xylose. These groups were maintained for two weeks. The effects of D-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic beta-cells were analyzed. RESULTS: In vivo, D xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. D-Xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of D-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with D-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, D-xylose exerted anti diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, D-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by beta-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D. PMID- 26865913 TI - Vitamin A supplementation modifies the antioxidant system in rats. AB - BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats. PMID- 26865914 TI - Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation. AB - BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl <= FBG <= 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on NFkappaB associated inflammatory response (phosphorylated inhibitory kappa B-alpha, interleukin 1beta, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor beta-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: The results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications. PMID- 26865915 TI - Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet induced obese mice. AB - BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-1beta and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells. PMID- 26865916 TI - The extended Theory of Planned Behavior in explaining exclusive breastfeeding intention and behavior among women in Kelantan, Malaysia. AB - BACKGROUND/OBJECTIVES: The purpose of this study is to utilize an extended Theory of Planned Behavior in identifying predictors of exclusive breastfeeding intention and behavior among women in Kelantan, Malaysia. SUBJECTS/METHODS: A prospective cohort study was conducted, recruiting pregnant womenthrough two stage cluster sampling. Their exclusive breastfeeding intention, attitude, perceived norm, perceived behavioral control and past behavior were obtained at baseline through interviewer-guided questionnaire. At one month after delivery, another interview was conducted to determine the two additional variables in the extended theory, which were their postpartum support and breastfeeding difficulty. The behavior, which was the actual duration of exclusive breastfeeding, was obtained from the second follow-up at six months. Pearson correlation and two hierarchical regression analyses were conducted. RESULTS: A total of 200 women completed the study follow-up. Their median intended exclusive breastfeeding duration was 4.0 (IQR 5) months, and the median actual duration was 1.0 (IQR 4) month. The Theory of Planned Behavior explained 51.0% of the variance in intention, with perceived behavioral control and attitude were the significant predictors. It also explained 10.0% of the variance in behavior, but the addition of postpartum support and breastfeeding difficulty increased the amount of explained variance in behavior by 6.0%. The significant predictors of exclusive breastfeeding behavior were intention, postpartum support and breastfeeding difficulty. CONCLUSION: The extended Theory of Planned Behaviorhad a good predictive ability in explaining exclusive breastfeedingintention and behavior. The women's intention to practice exclusive breastfeeding may be improved by improving their perceived behavioral control and attitude. Providing correct postpartum support and skills to handle breastfeeding difficulties after delivery will improve their exclusive breastfeeding behavior. PMID- 26865917 TI - Modelling protection behaviour towards micronutrient deficiencies: Case of iodine biofortified vegetable legumes as health intervention for school-going children. AB - BACKGROUND/OBJECTIVES: Despite successes recorded in combating iodine deficiency, more than 2 billion people are still at risk of iodine deficiency disorders. Rural landlocked and mountainous areas of developing countries are the hardest hit, hence the need to explore and advance novel strategies such as biofortification. SUBJECTS/METHODS: We evaluated adoption, purchase, and consumption of iodine biofortified vegetable legumes (IBVL) using the theory of protection motivations (PMT) integrated with an economic valuation technique. A total of 1,200 participants from three land-locked locations in East Africa were recruited via multi-stage cluster sampling, and data were collected using two, slightly distinct, questionnaires incorporating PMT constructs. The survey also elicited preferences for iodine biofortified foods when offered at a premium or discount. Determinants of protection motivations and preferences for iodine biofortified foods were assessed using path analysis modelling and two-limit Tobit regression, respectively. RESULTS: Knowledge of iodine, iodine-health link, salt iodization, and biofortification was very low, albeit lower at the household level. Iodine and biofortification were not recognized as nutrient and novel approaches, respectively. On the other hand, severity, fear, occupation, knowledge, iodine status, household composition, and self-efficacy predicted the intention to consume biofortified foods at the household level; only vulnerability, self-efficacy, and location were the most crucial elements at the school level. In addition, results demonstrated a positive willingness-to-pay a premium or acceptance of a lesser discount for biofortification. Furthermore, preference towards iodine biofortified foods was a function of protection motivations, severity, vulnerability, fear, response efficacy, response cost, knowledge, iodine status, gender, age. and household head. CONCLUSIONS: Results lend support for prevention of iodine deficiency in unprotected populations through biofortification; however 'threat' appraisal and socio-economic predictors are decisive in designing nutrition interventions and stimulating uptake of biofortification. In principle, the contribution is threefold: 1) Successful application of the integrated model to guide policy formulation; 2) Offer guidance to stakeholders to identify and tap niche markets; 3) stimulation of rural economic growth around school feeding programmes. PMID- 26865918 TI - Association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome in Korean women with type 2 diabetes mellitus. AB - BACKGROUND/OBJECTIVES: This study was aimed at examining the association between dietary flavanones intake and lipid profiles according to the presence of metabolic syndrome (MetS) in Korean women with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: A cross-sectional analysis was performed among 502 female T2DM patients (non-MetS group; n = 129, MetS group; n = 373) who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) and the data was analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. The intake of flavanones was estimated on the basis of the flavonoid database. RESULTS: In the multiple linear regression analysis after adjustment for confounding factors, daily flavanones intake was negatively associated with CVD risk factors such as total cholesterol, LDL cholesterol, and apoB and apoB/apoA1 ratio only in the MetS group but not in the non-MetS group. Multiple logistic regression analysis revealed that the odds ratio for a higher apoB/apoA1 ratio above the median (>= 0.74) was significantly low in the 4(th) quartile compared to that in the 1(st) quartile of dietary flavanones intake [OR: 0.477, 95% CI: 0.255-0.894, P for trend = 0.0377] in the MetS group. CONCLUSIONS: Dietary flavanones intake was inversely associated with the apoB/apoA1 ratio, suggesting a potential protective effect of flavanones against CVD in T2DM women with MetS. PMID- 26865919 TI - Combined effect of folate and adiposity on homocysteine in children at three years of age. AB - BACKGROUND/OBJECTIVES: Cardiovascular diseases is a major cause of death and is responsible for 23.8% of deaths in Korea. Clinical symptoms manifest in adulthood, but susceptibility begins in utero. Elevated homocysteine levels and adiposity might be linked to a greater risk in children as well as adults. We hypothesized that those who have simultaneous risk for folate and adiposity would be affected with elevated homocysteine levels at 3 years of age. SUBJECTS/METHODS: From the ongoing birth cohort at Ewha Womans University Mok Dong Hospital, we compared adiposity parameters, serum homocysteine, and folate levels in 238 children (118 boys and 120 girls) at three years of age. The relationship between birth outcome, current weight and body mass index (BMI), postnatal growth, and homocysteine level were assessed using correlation and general linear model. Additionally, we assessed the combined effect between blood folate status and adiposity on current homocysteine levels. RESULTS: Birth characteristics were not correlated with homocysteine. Current weight, BMI, upper arm circumference, skinfold thickness, waist circumference, and hip circumference were positively correlated with homocysteine at three years of age (P < 0.05). Folate level was negatively correlated with homocysteine at three years of age (P < 0.0001). A relative high anthropometric measure which is compatible with adiposity and low folate level was associated with high homocysteine levels. CONCLUSION: We found a combined effect of adiposity and folate levels with homocysteine levels at three years of age. This implicates the beneficial role of folate supplementation in the high-risk population at an early age. PMID- 26865920 TI - Dietary factors associated with high serum ferritin levels in postmenopausal women with the Fifth Korea National Health and Nutrition Examination Survey (KNHANES V), 2010-2012. AB - BACKGROUND/OBJECTIVES: Serum ferritin levels are significantly increased after menopause and greatly affect women's health. The aim of this study was to investigate the dietary and non-dietary factors associated with high ferritin levels in postmenopausal women. SUBJECTS/METHODS: Among adult women in 2010-2012, qualified postmenopausal women (n = 3880) were separated into quartiles of serum ferritin. The variable differences among the quartiles of ferritin were determined using either procsurvey chi-square test (chi(2)-test) among categorical variables, or GLM (Generalized Linear Model) among continuous variables. The odds ratio for high ferritin in relation to dietary factors was also determined using procsurvery logistic analysis. RESULTS: Age, obesity, drinking habit, and blood glucose levels were found to be significant indicators of high serum ferritin level after adjusting for all confounding factors. Among the food groups, grain, milk, vegetable, and seaweed intakes were significantly associated with high ferritin levels, but after adjusting for all confounding factors, only grains and vegetables remained significant factors. Among the nutrient groups, calcium, vitamin A, and vitamin C intake were significant factors, but after adjustment, none of the nutrient groups analyzed were associated with a high risk of ferritin. CONCLUSION: Age, obesity, drinking habit, and glucose levels, as well as inadequate intakes of grains and vegetables, were found to be significantly associated with high serum ferritin levels in postmenopausal Korean women. PMID- 26865921 TI - Vegetable intake is associated with lower Frammingham risk scores in Korean men: Korea National Health and Nutrition Survey 2007-2009. AB - BACKGROUND/OBJECTIVES: Observational studies suggest that an association between vegetable consumption and coronary heart disease (CHD). However, the results are inconsistent. This study aimed to investigate the daily intake of vegetables on a national level and its effect on the risk of CHD risk, as determined by the Framingham Risk Score (FRS). SUBJECTS/METHODS: This study was conducted a cross sectional design of 2,510 male adults 40-64y of age who participated in the 2007 2009 Korean National Health and Nutrition Examination Survey. Daily intake of vegetable was assessed by 24-h recall, and the consumption frequency of vegetables was determined using a food frequency questionnaire. The odd ratio of CHD risk according to daily intake and frequency of vegetables was analyzed. RESULTS: Total vegetable intake was inversely and significantly associated with the risk of CHD (Model 1: 4th vs. 1st quartile, OR = 0.74, 95% CI = 0.58-0.96, P for trend = 0.0015), and the significant relationship with CHD risk remained even after adjusting for potential confounders (Model 3: 4th vs. 1st quartile, adjusted OR [aOR] = 0.69, 95% CI = 0.49-0.95, P for trend = 0.0492). Subjects in the higher quartiles of non-salted vegetable intake had 31% lower odds of the risk of CHD compared to those in the lowest quartile after adjusting for various potential confounders in model 3 (aOR = 0.69; 95% CI = 0.49-0.97, P for trend = 0.0478). No significant associations between the frequency of vegetable intake (total, green, white and red vegetable) and the risk of CHD were found. CONCLUSIONS: The major results of this study indicate that higher vegetable intake may help prevent CHD in Korean men. PMID- 26865922 TI - Development and evaluation of continuing education course in renal nutrition. AB - BACKGROUND/OBJECTIVE: Competent renal dietitians are crucial for better patient compliance and clinical outcomes, specifically in critical settings. The aim of this study was to develop and evaluate an evidence-based course in renal dietetics for dietitians working in health care systems where dietetic specialization is absent. SUBJECTS/METHODS: Fifteen licensed dietitians working with hemodialysis patients in Lebanon were randomly recruited to participate in the course. The latter was developed by the study's primary investigator, according to evidence-based practice guidelines, and focused on all aspects of renal nutrition. Total course duration was 28 hours spread over a 2 month period. Dietitians' knowledge in renal nutrition was tested pre- and post-training through a 23-item questionnaire; the total score was expressed in percentage (< 60% score indicated insufficient knowledge). Paired-samples t test was used for statistical analysis. RESULTS: Overall knowledge of the dietitians significantly improved post-training and reached satisfactory levels (pre: 38.75 +/- 17.20%, post: 62.08 +/- 21.85%). Sub-analysis of the change in the knowledge showed significant and satisfactory improvement only in 3 topics: 1) correct body weight use in calculations, 2) energy estimation method and 3) phosphorus management. Knowledge in the fluid management significantly improved but did not achieve a satisfactory level. CONCLUSION: The course significantly improved dietitians' knowledge in renal nutrition. If adopted as part of the continuing education of dietitians in countries that lack dietetic specializations, it may serve the first step towards improving health care practice. PMID- 26865923 TI - Consumer perceptions on sustainable practices implemented in foodservice organizations in Korea. AB - BACKGROUND/OBJECTIVES: Sustainable practices in foodservice organizations including commercial and noncommercial ones are critical to ensure the protection of the environment for the future. With the rapid growth of the foodservice industry, wiser usage of input sources such as food, utilities, and single use packaging should be reconsidered for future generations. Therefore, this study aims to investigate the customer's perceptions on sustainable practices and to identify the relationship among sustainable practices, social contribution and purchase intention. SUBJECTS/METHODS: The study was conducted using content analyses by reviewing articles on sustainable food service practices published domestically and abroad. Thereafter, data were collected with a face-to-face survey using a questionnaire and analyzed with factor analyses and multiple regressions. RESULTS: Sustainable practices classified with factor analysis consisted of 6 dimensions of green food material procurement, sustainable food preparation, green packaging, preservation of energy, waste management, and public relations on green activity, with a total of 25 green activities in foodservice operations. Consumers were not very familiar with the green activities implemented in the foodservice unit, with the lowest awareness of "green food material procurement (2.46 out of 5 points)", and the highest awareness of "green packaging (3.74)" and "waste management (3.28). The factors influencing the perception of social contribution by foodservice organizations among 6 sustainable practice dimensions were found to be public relations on green activity (beta = 0.154), waste management (beta = 0.204) and sustainable food preparation (beta = 0.183). Green packaging (beta = 0.107) and the social contribution of the foodservice organization (beta = 0.761) had strong relationships with the image of the organization. The purchase intentions of customers was affected only by the foodservice image (beta = 0.775). CONCLUSIONS: The results of this study suggest that sustainable practices by foodservice organization present a good image to customers and increase the awareness of valuable contributions that benefit the customer as well as the community. PMID- 26865924 TI - Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight. AB - BACKGROUND/OBJECTIVES: This is the first study to identify common genetic factors associated with the basal metabolic rate (BMR) and body mass index (BMI) in obese Korean women including overweight. This will be a basic study for future research of obese gene-BMR interaction. SUBJECTS/METHODS: The experimental design was 2 by 2 with variables of BMR and BMI. A genome-wide association study (GWAS) of single nucleotide polymorphisms (SNPs) was conducted in the overweight and obesity (BMI > 23 kg/m(2)) compared to the normality, and in women with low BMR (< 1426.3 kcal/day) compared to high BMR. A total of 140 SNPs reached formal genome-wide statistical significance in this study (P < 1 * 10(-4)). Surveys to estimate energy intake using 24-h recall method for three days and questionnaires for family history, a medical examination, and physical activities were conducted. RESULTS: We found that two NRG3 gene SNPs in the 10q23.1 chromosomal region were highly associated with BMR (rs10786764; P = 8.0 * 10(-7), rs1040675; 2.3 * 10( 6)) and BMI (rs10786764; P = 2.5 * 10(-5), rs10786764; 6.57 * 10(-5)). The other genes related to BMI (HSD52, TMA16, MARCH1, NRG1, NRXN3, and STK4) yielded P <10 * 10(-4). Five new loci associated with BMR and BMI, including NRG3, OR8U8, BCL2L2-PABPN1, PABPN1, and SLC22A17 were identified in obese Korean women (P < 1 * 10(-4)). In the questionnaire investigation, significant differences were found in the number of starvation periods per week, family history of stomach cancer, coffee intake, and trial of weight control in each group. CONCLUSION: We discovered several common BMR- and BMI-related genes using GWAS. Although most of these newly established loci were not previously associated with obesity, they may provide new insights into body weight regulation. Our findings of five common genes associated with BMR and BMI in Koreans will serve as a reference for replication and validation of future studies on the metabolic rate. PMID- 26865926 TI - Comparative pharmacokinetic evaluation and bioequivalence study of three different formulations of Imatinib Mesylate in CML patients. AB - BACKGROUND: Imatinib is known as the drug of choice for treatment of chronic myeloid leukemia (CML). For adults the recommended daily dosage of 400 mg requires simultaneous intake of up to four capsules or tablets each 100 mg. A new 400 mg film coated tablet developed due to the need to swallow multiple capsules or tablets per dose and that was a negative impact on treatment adherence. SUBJECTS AND METHODS: A group of 36 patients were randomly assigned to receive Imatinib as 4*100 mg capsules, 4*100 mg tablets and 1*400 mg tablet. Blood sampling was performed for up to 48 h after first dosing. After that, subjects were monitored to assess drug related adverse events. Pharmacokinetic parameters were assessed using concentration-time curves for plasma Imatinib and its metabolite. RESULTS: Mean area under the curve (AUC (0-infinity)) values were 27011, 25811 and 25699 ng/ml for 4*100 mg capsules, 4*100 mg tablets and 1*400 mg tablets, respectively. Cmax values were 1548, 1605 and 1622 ng/ml and t1/2 values were 15.7, 15.8 and 15.6 h. The Test/Reference ratios for AUC (0-infinity), AUC (0-48), and Cmax were 0.99, 0.99 and 1.02 for 4*100 mg tablets versus 4*100 mg capsules and 0.96, 0.96 and 0.99 for 1*400 mg tablet versus 4*100 mg capsules. The 95% confidence intervals were fully contained within the accepted interval. The mild and moderate adverse events considered to be drug related were reported. These events showed no clustering by type of dosage form and were of little to no clinical significance. CONCLUSION: Film coated (400 mg) tablet dosage formulations of Imatinib is bioequivalent to the commercial available 100 mg hard gelatin capsule, and is as safe and well tolerated. PMID- 26865925 TI - Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly. AB - Lack of structure is often an essential functional feature of protein domains. The coordination of macromolecular assemblies in DNA repair pathways is yet another task disordered protein regions are highly implicated in. Here I review the available experimental and computational data and within this context discuss the functional role of structure and disorder in one of the essential scaffolding proteins in the nucleotide excision repair (NER) pathway, namely Xeroderma pigmentosum complementation group A (XPA). From the analysis of the current knowledge, in addition to protein-protein docking and secondary structure prediction results presented for the first time herein, a mechanistic framework emerges, where XPA builds the NER pre-incision complex in a modular fashion, as "beads on a string", where the protein-protein interaction "beads", or modules, are interconnected by disordered link regions. This architecture is ideal to avoid the expected steric hindrance constraints of the DNA expanded bubble. Finally, the role of the XPA structural disorder in binding affinity modulation and in the sequential binding of NER core factors in the pre-incision complex is also discussed. PMID- 26865927 TI - Effects of short-term pretreatment with atorvastatin on mobilization of hematopoietic progenitor cells: A double-blind, randomized, controlled trial. AB - BACKGROUND: Despite recent advances in mobilization techniques, a considerable portion of patients fail to mobilize sufficient number of cells for successful autologous stem cell transplantation. There are several studies available that have demonstrated enhanced mobilization of endothelial progenitor cells with atorvastatin. Therefore, this prospective trial was conducted to evaluate the mobilizing effect of atorvastatin on hematopoietic progenitor cells. SUBJECTS AND METHODS: Forty-four autologous HSCT candidates were randomized in a double-blind controlled trial to receive atorvastatin 40 mg daily or placebo plus standard G CSF regimen. Treatment was initiated at the time of hospitalization and continued until the day of cell harvest. Independent-samples T-Test, Repeated Measures ANOVA and Mann-Whitney U test were performed to compare means. Categorical variables were analyzed using Chi-square and Fisher's exact test. RESULTS: Mean number of hematopoietic progenitor cells per microL of peripheral blood at the time of cell harvest did not differ significantly between the two groups. There was no statistically significant difference in secondary outcomes like time of platelet or PMN engraftment, occurrence of bleeding or infectious episode, duration of hospitalization and etc. CONCLUSION: The results of this study did not support beneficial effects of atorvastatin on mobilization of hematopoietic progenitor cells from bone marrow. PMID- 26865928 TI - Concentration Study of High Sensitive C - reactive Protein and some Serum Trace Elements in Patients with Benign and Malignant Breast Tumor. AB - Background : Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. SUBJECTS AND METHODS: A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05. RESULTS: Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000). Conclusion : Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease. PMID- 26865929 TI - Identification of CYP2C9 and VKORC1 polymorphisms in Iranian patients who are under warfarin therapy. AB - BACKGROUND: Although catalytic properties of different genetic polymorphisms of VKORC1 and CYP2C9 products have been identified, there is limited study available regarding warfarin dose requirement in Iranian patient population. This study investigates the impact of these polymorphisms on 115 patients, referred to Payvand Clinical and Specialty Laboratory for determining the appropriate dose of warfarin. RESULTS of the study may be applicable to individuals who are under warfarin therapy to avoid warfarin resistance or intolerance. SUBJECTS AND METHODS: PT-INR test was utilized as a screening method. Genotyping were performed for VKORC1 and CYP2C9 using PCR method. Statistical analyses including unpaired t-test or ANOVA and regression were done using SPSS. RESULTS: VKORC1 GA was the most common genotype of VKORC1 allele among the study samples, with a rate of 57.4%. In CYP2C9 variant, 20% and 14.8% of subjects carried CYP2C9*1/*2 and CYP2C9*1/*3 genotyping, respectively. By contrast, the WT *1/*1 genotype was more abundant and dominant. The high frequency of VKORC1 (_1639) GA genotype (57.4%), was significant versus for the rest of the cohort (42.6%). In addition, a significant relationship was found between CYP2C9*1 and drug dose (P>0.021). CONCLUSION: In this study, samples were characterized by higher frequencies of CYP2C9*1 and VKORC1 G/A, determined as higher warfarin taking doses. The results showed a significant relationship of the VCORC1 and CYP2C9 polymorphisms with warfarin sensitivity and severe side effects. Estimating right doses of warfarin to prescribe can help to reduce the risk of over- or under-anticoagulation and subsequently, the risk of thromboembolism or bleeding. PMID- 26865930 TI - Bone marrow infiltration in Langerhan's cell histiocytosis - An unusual but important determinant for staging and treatment. AB - BACKGROUND: Langerhans' cell histiocytosis (LCH) is a reactive proliferative disease of unknown pathogenesis characterized by proliferation of Langerhans cells. Involvement of bone marrow (BM), liver and lung are related to high risk factors and poor survival. The aim of this report is to highlight the clinical and haematological findings of 5 cases of LCH with BM infiltration which may help to predict involvement of BM. CASE SERIES: Five cases of Langerhan's cell histiocytosis with bone marrow infiltration were retrieved from archives of Department of Hematology, PGIMER and Chandigarh for review and further analysis. Male to female ratio was 3:2 with mean age of 9.4 months. Two out of 5 patients had obvious skull swelling; however, radiography of the skull revealed lytic lesion of skull in 4 cases and 2 had skin rashes. Hepatomegaly was present in 4 cases and 2 of whom also had lymphadenopathy and splenomegaly. All patients had anaemia at the time of presentation. Bone marrow aspiration and trephine biopsy in all 5 cases revealed infiltration by large histiocytes with abundant cytoplasm and coffee bean shaped nucleus. Nodules of these Langerhans cells with admixture of eosinophils were seen on trephine biopsy. Immunohistochemistry showed positivity for CD1a stain. CONCLUSION: BM evaluation is important in LCH patients to categorize disease which further determines the type of therapy to be given. Clinical details may help to predict the BM involvement; however, demonstration of CD1a positive cells in marrow is most important tool to diagnose marrow infiltration by LCH. PMID- 26865931 TI - A Large Cohort Study of Genotype and Phenotype Correlations of Beta- Thalassemia in Iranian Population. AB - BACKGROUND: Thalassemia syndromes are the most prevalent single gene disorders in Iran. This study aimed to evaluate the effect of different types of beta-globin gene mutations, co-inheritance of alpha-globin gene mutations and/or Xmn1 SNP on disease phenotype in a large cohort of Iranian patients. SUBJECTS AND METHODS: In total, 433 patients were clinically classified into beta-thalassemia major (TM) or intermedia (TI). Multiplex PCR, ARMS-PCR, RFLP-PCR and DNA sequencing were performed to identify both alpha- and beta-globin gene mutations and Xmn1 polymorphism as well. All data were compared and analyzed by SPSS software in TM and TI groups, consequently. RESULTS: A total of 39 different beta-globin mutations were identified. Among them, the most common were IVS IInt1 (40.33%) followed by IVS Int5 (9.56%), C30 (7.22%) and Fr8-9(7%). All patients were subjected to evaluate common alpha-globin gene deletions. The patients inherited concomitant mutations of alpha- and beta-globin, showed no clinical modifications compared with those who had only beta-globin mutation. The TI patients showed a significant increase in frequency of both heterozygous and homozygous form of the Xmn1 polymorphism. It was also found that beta(0)/beta(0) genotype patients, inherited the Xmn1 polymorphism required lesser blood transfusion. CONCLUSION: No significant differences were observed, on the severity of disease, between patient's inherited defective alpha- and beta-globin genes and ones with just beta-globin gene mutation. Taking the results of this research into account, Xmn1 polymorphism can be considered as an important genetic factor modulating the severity of disease. PMID- 26865932 TI - The Role of HDACs as Leukemia Therapy Targets using HDI. AB - Histone deacetylases (HDACs) are the enzymes causing deacetylation of histone and non-histone substrates. Histone deacetylase inhibitors (HDIs) are a family of drugs eliminating the effect of HDACs in malignant cells via inhibition of HDACs. Due to extensive effects upon gene expression through interference with fusion genes and transcription factors, HDACs cause proliferation and migration of malignant cells, inhibiting apoptosis in these cells via tumor suppressor genes. Over expression evaluation of HDACs in leukemias may be a new approach for diagnosis of leukemia, which can present new targets for leukemia therapy. HDIs inhibit HDACs, increase acetylation in histones, cause up- or down regulation in some genes and result in differentiation, cell cycle arrest and apoptosis induction in malignant cells via cytotoxic effects. Progress in identification of new HDIs capable of tracking several targets in the cell can result in novel achievements in treatment and increase survival in patients. In this review, we examine the role of HDACs as therapeutic targets in various types of leukemia as well as the role of HDIs in inhibition of HDACs for treatment of these malignancies. PMID- 26865934 TI - Correction: GDP versus ESHAP Regimen in Relapsed and/or Refractory Hodgkin lymphoma: A Comparison Study. PMID- 26865933 TI - Treatment related acute promyelocytic leukemia (t-APML) in breast cancer survivor treated with anthracycline based chemotherapy: rare case report. AB - Treatment related acute myeloid leukemia (t-AML) is well documented phenomenon after chemotherapy. In this subgroup of patients acute promyelocytic leukemia (APML) due to delayed complication of using anthracycline is very rare occurrence. Very few cases are reported in world literature. We are reporting a rare case of occurrence of t-APML in cured breast cancer patient treated with doxorubicin. 43 year old female presented with triple negative early breast cancer treated initially with Right modified radical mastectomy. Pathological staging was pT2N0M0. She was treated with 6 cycle of adjuvant AC (Doxorubicin, Cyclophosphamide). After latent period of 23 months she developed symptoms of fever, weakness and generalized body ache. On further investigation she was found to have acute promyelocytic leukemia (APML). We had successfully treated t-APML with conventional 7+3 induction and subsequent consolidation with ATRA (All Trans Retinoic Acid) and arsenic trioxide. Patient was given maintenance treatment for 18 months after confirming negative PML RARA by RT PCR and declared cured. Patient is under regular surveillance in our centre. PMID- 26865935 TI - Detection, Virulence Gene Assessment and Antibiotic Resistance Pattern of O157 Enterohemorrhagic Escherichia coli in Tabriz, Iran. AB - BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen and infection with this organism causes illnesses such as bloody diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome. OBJECTIVES: Considering the lack of any information about the prevalence rate and the antibiotic resistance pattern of O157:H7 serotype in Tabriz, finding answers to the above mentioned subjects was among the goals of this study. MATERIALS AND METHODS: Two hundred E. coli strains from diarrheal or non-diarrheal stools of outpatients and hospitalized cases in Tabriz Imam Reza hospital were isolated between September and December 2014 using MacConkey agar and standard biochemical tests and then cultured on sorbitol MacConkey agar. The sorbitol-negative isolates were confirmed as the O157 serotype using O157 antisera. A multiplex polymerase chain reaction (PCR) method was used for the detection of stx-1, stx 2, eae, and mdh genes and the antibiotic resistance pattern of these isolates was determined using Kirby-Bauer method and clinical and laboratory standards institute (CLSI) standards. RESULTS: Of the isolates 11 (5.5%) were sorbitol negative, which were later analyzed by multiplex PCR and the results revealed that 2 (18.18%) isolates contained the stx-1 gene, 10 (90.91%) contained the stx 2 gene, and 5 (45.45%) contained the eae gene. The stx-2 and eae genes were the most commonly encountered virulence factors. All or most of the isolates were susceptible to ceftazidime (100%), gentamicin (100%), ciprofloxacin (100%), nalidixic acid (90.9%), trimetoprim sulfamethoxazole (90.9%), chloramphenicol (90.9%), ampicillin (81.8%), and cephalothin (72.7%). On the contrary, moderate susceptibility of the isolates to doxycycline (54.5%) was observed. CONCLUSIONS: Due to the low frequency of STEC O157 and the high susceptibility rates of the isolates to the tested antibiotics in this study, STEC O157 has not become a major problem in Tabriz yet, but comprehensive microbiological surveillance programs that provide early warning and limit the scale of possible outbreaks would be essential. PMID- 26865936 TI - Isolation and Characterization of a Myoviridae MJ1 Bacteriophage Against Multi Drug Resistant Escherichia coli 3. AB - BACKGROUND: Antibiotic resistance in Escherichia coli, a member of the Enterobacteriaceae, is of particular concern because it is the most common (Gram negative) pathogen causing nosocomial and community infections. Researchers are now considering the use of phages for the control of various antibiotic-resistant bacterial infections. OBJECTIVES: The purpose of this study was to isolate and characterize a novel pathogenic/lytic phage that targets multi-drug resistant (MDR) E. coli 3, and to investigate its effectiveness at lysing this bacterium. MATERIALS AND METHODS: A clinical strain of E. coli 3 was identified based on its 16S rRNA sequencing and its antibiotic resistance profile was determined by the disc diffusion method. A bacteriophage was isolated from wastewater and its various characteristics, such as host range, heat tolerance, pH stability, one step growth, total protein content, and genome size, were determined. The antibacterial property of the phage was determined against log-phase bacterial planktonic cells at 37 degrees C. RESULTS: The bacteriophage, designated MJ1, was isolated by testing against a clinical MDR E. coli 3 strain. The MJ1 phage showed a wide range of heat and pH stability. The phage morphology, determined by transmission electron microscopy, revealed a structure comprised of a head (108 +/- 0.2 nm long by 128 +/- 0.5 nm wide) and a contractile tail (123 +/- 0.5 nm long by 15 - 26 nm wide). These features placed the MJ1 phage in the family Myoviridae and the order Caudovirales. Eleven structural proteins (17 to 200 kDa) for this phage were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A double stranded DNA, approximately 32 kb, in size was detected for this phage on agarose gels. The phage efficacy against E. coli 3 planktonic cells was also investigated. The MJ1 phage demonstrated a very good capability to reduce the numbers of E. coli 3 planktonic cells, as determined by a change in the bacterial growth (an optical density decrease at 600 nm from 0.40 to 0.12). CONCLUSIONS: MJ1 phage has much potential for use in phage therapy and other applications. PMID- 26865937 TI - Investigation of OprD Porin Protein Levels in Carbapenem-Resistant Pseudomonas aeruginosa Isolates. AB - BACKGROUND: The Pseudomonas aeruginosa porin OprD is a substrate-specific porin that facilitates the diffusion of basic amino acids, small peptides, and carbapenems into the cell. OprD-mediated resistance occurs as a result of decreased transcriptional expression of oprD and/or loss of function mutations that disrupt protein activity. OBJECTIVES: In this study, we examined the level of oprD expression in P. aeruginosa clinical isolates to determine the contribution of OprD porins in carbapenem resistance. MATERIALS AND METHODS: Included strains were divided into two groups, comprised of multidrug-resistant (MDR) and isolated carbapenem-resistant (ICR) strains. The transcription product level of oprD was identified using real-time polymerase chain reaction (qPCR). RESULTS: Of the 18 clinical isolates, a decrease in the oprD level was found to be significant in 13 isolates. Nine of eighteen isolates with a significant decrease were determined in the first group and comprised MDR isolates that showed a statistically significant difference compared with the ICR group (P = 0.001). In the ICR group, oprD levels were found to be significantly low in 4 isolates. Six different patterns were determined by comparing band profiles in AP PCR. CONCLUSIONS: Although the data support the idea that the basic mechanism of imipenem resistance could be via the loss of oprD, they do not fully explain the role of oprD and indicate that other mechanisms may play an important role. Additionally, the significant decrease in the oprD levels in MDR strains suggests that oprD also plays a role in the emergence of both carbapenem and non carbapenem resistance. PMID- 26865938 TI - Design, Construction and Cloning of Truncated ORF2 and tPAsp-PADRE-Truncated ORF2 Gene Cassette From Hepatitis E Virus in the pVAX1 Expression Vector. AB - BACKGROUND: Hepatitis E Virus (HEV) is the causative agent of enterically transmitted acute hepatitis and has high mortality rate of up to 30% among pregnant women. Therefore, development of a novel vaccine is a desirable goal. OBJECTIVES: The aim of this study was to construct tPAsp-PADRE-truncated open reading frame 2 (ORF2) and truncated ORF2 DNA plasmid, which can assist future studies with the preparation of an effective vaccine against Hepatitis E Virus. MATERIALS AND METHODS: A synthetic codon-optimized gene cassette encoding tPAsp PADRE-truncated ORF2 protein was designed, constructed and analyzed by some bioinformatics software. Furthermore, a codon-optimized truncated ORF2 gene was amplified by the polymerase chain reaction (PCR), with a specific primer from the previous construct. The constructs were sub-cloned in the pVAX1 expression vector and finally expressed in eukaryotic cells. RESULTS: Sequence analysis and bioinformatics studies of the codon-optimized gene cassette revealed that codon adaptation index (CAI), GC content, and frequency of optimal codon usage (Fop) value were improved, and performance of the secretory signal was confirmed. Cloning and sub-cloning of the tPAsp-PADRE-truncated ORF2 gene cassette and truncated ORF2 gene were confirmed by colony PCR, restriction enzymes digestion and DNA sequencing of the recombinant plasmids pVAX-tPAsp-PADRE-truncated ORF2 (aa 112-660) and pVAX-truncated ORF2 (aa 112-660). The expression of truncated ORF2 protein in eukaryotic cells was approved by an Immunofluorescence assay (IFA) and the reverse transcriptase polymerase chain reaction (RT-PCR) method. CONCLUSIONS: The results of this study demonstrated that the tPAsp-PADRE truncated ORF2 gene cassette and the truncated ORF2 gene in recombinant plasmids are successfully expressed in eukaryotic cells. The immunogenicity of the two recombinant plasmids with different formulations will be evaluated as a novel DNA vaccine in future investigations. PMID- 26865939 TI - The Effect of Campylobacter concisus on Expression of IL-18, TNF-alpha and p53 in Barrett's Cell Lines. AB - BACKGROUND: Barrett's oesophagus is a pre-malignant condition at gastroesophageal junction in which normal squamous epithelium is replaced by columnar shape epithelium, which predisposes oesophageal adenocarcinoma. It is known that Barrett's oesophagus evolves as a consequence of chronic gastro-oesophageal reflux disease. Although progression of Barrett's oesophagus to adenocarcinoma is still unclear, increasing incidence of oesophageal cancer and mortality worldwide make its study necessary. Several investigations have been made on the aetiology of oesophageal cancer. Most of them assessed genetical or environmental factors. However, potential role of bacteria in the development of oesophageal adenocarcinoma as a new environmental factor has not been addressed. Previous study on Barrett's disease detected presence of Campylobacter concisus as a new emerging pathogen on Barrett's and oesophageal cancer samples compared with healthy individuals. This indicates that this organism might involve in the progression of Barrett's to oesophageal adenocarcinoma. OBJECTIVES: This study aimed to determine the effects of C. concisus on expression of three biomarkers including interleukin-18 (IL-18), tumour necrosis factor-alpha (TNF-alpha) and tumour suppressor gene (p53) in three Barrett's cell lines. MATERIALS AND METHODS: Quantitative real-time PCR assays were developed to measure expression of pro-inflammatory mediators (IL-18 and TNF-alpha) and gene expression of p53 in Barrett's cell lines in co-culture with C. concisus. RESULTS: The mentioned organism was able to modulate considerably expression of p53, TNF-alpha and IL-18 in a time-dependent manner. CONCLUSIONS: The results showed that microorganism influences expression of carcinogenesis biomarker and cytokines in cell line models and possibility promotes oesophageal adenocarcinoma. PMID- 26865940 TI - Detection and Typing of Human Papilloma Viruses by Nested Multiplex Polymerase Chain Reaction Assay in Cervical Cancer. AB - BACKGROUND: Cervical cancer is the leading cause of death from cancer in under developed countries. Human papilloma virus (HPV) 16 and 18 are the most prevalent types associated with carcinogenesis in the cervix. Conventional Polymerase Chain Reaction (PCR), type-specific and consensus primer-based PCR followed by sequencing, Restriction Fragment Length Polymorphism (RFLP) or hybridization by specific probes are common methods for HPV detection and typing. In addition, some researchers have developed a multiplex PCR for simultaneous detection and typing of different HPVs. OBJECTIVES: The aim of the present study was to investigate the prevalence of HPV infection and its types in cervical Squamous Cell Carcinoma (SCC) using the Nested Multiplex PCR (NMPCR) assay. PATIENTS AND METHODS: Sixty-six samples with histologically confirmed SCC were evaluated. Total DNA was isolated by phenol-chloroform extraction and ethanol precipitation. Nested multiplex PCR was performed with first-round PCR by GP-E6/E7 consensus primers for amplification of the genomic DNA of all known mucosal HPV genotypes and second-round PCR by type-specific multiplex PCR primer cocktails. RESULTS: Human papilloma virus infection was detected in 78.8% of samples, with the highest prevalence of HPV 16 (60.6%) while concurrent infections with two types was detected in 10.6%. CONCLUSIONS: The NMPCR assay is more convenient and easy for analysis of results, which is important for fast diagnosis and patient management, in a type-specific manner. PMID- 26865941 TI - Evaluation of mRNA Expression Levels of cyp51A and mdr1, Candidate Genes for Voriconazole Resistance in Aspergillus flavus. AB - BACKGROUND: Voriconazole Resistance (VRC-R) in Aspergillus flavus isolates impacts the management of aspergillosis, since azoles are the first choice for prophylaxis and therapy. However, to the best of our knowledge, the mechanisms underlying voriconazole resistance are poorly understood. OBJECTIVES: The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique. MATERIALS AND METHODS: Five A. flavus isolates with resistance to VRC were examined by a RT-PCR approach. RESULTS: Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction. CONCLUSIONS: Our experimental and in silico findings may provide new insight in the complex molecular pathways of drug resistance and also could assist design an efficient therapeutic strategy for aspergillosis treatment. PMID- 26865942 TI - Evaluation of Immune Response Against Inactivated Avian Influenza (H9N2) Vaccine, by Using Chitosan Nanoparticles. AB - BACKGROUND: Influenza A is a virus that affects a wide range of animals and also human beings. Avian influenza virus (AIV) subtype H9N2 has the potential to create influenza pandemic and vaccination is a common solution for this problem. The vaccine, used for rapid intervention, should be safe to use and highly effective, after a single administration. Chitosan nanoparticles (CNP) have already been recommended as a new adjuvant for inactivated AIV H9N2 vaccine immunization. OBJECTIVES: This study aimed at the evaluation and better understanding of optimum concentration of CNP preparations and also, assessment of loading capacity of AIV into CNP, as an adjuvant in specific pathogen-free (SPF) chickens. MATERIALS AND METHODS: For measurement of vaccine-antibody response, different types of CNP were injected intramuscularly, in a single dose, to 21-day-old specific pathogen-free chickens. Chickens were monitored for the efficacy of the nanoparticles and, also, their immune response, during a follow up of 7 weeks, by using hemagglutination-inhibition (HI) test. The CNP were prepared according to modified ionic gelation method and inactivated antigen was loaded in four hemagglutinin units (HAU) concentrations. Loading capacity of nanoparticles was determined by hemagglutination (HA) method. Inactivated A/H9N2 AIV was mixed with chitosan of low molecular weight. RESULTS: The CNP did not cause any mortality or side effects, when chickens were administered the prepared vaccine. The results strongly showed that this novel vaccine significantly enhances the immunogenicity of inactivated AIV, comparing with ISA70 (SEPPIC, Puteaux, France) adjuvant that is used routinely in the Razi Serum and Vaccine Research and Production Institute, Karaj, Iran, to reduce ISA70's side effects. CONCLUSIONS: The AIV loaded into CNP vaccines induce appropriate antibody titers, after a single immunization, while requiring a low dose of antigen. The CNP also represent an interesting new platform for antigen delivery and a promising adjuvant candidate for H9N2 inactivated influenza vaccine. PMID- 26865943 TI - Impact of Human Enterovirus 71 Genotypes in Meningoencephalitis in Iran. AB - BACKGROUND: Since the importance of poliovirus has diminished, as a result of its elimination in the majority of countries, non-polioviruses are emerging as causative agents of severe central nervous system (CNS) involvement. Outbreaks of enterovirus 71 (EV71)-associated CNS infections have recently been reported in Asia, Australia, and Europe. OBJECTIVES: This is the first study on genotyping of EV71 in children with meningoencephalitis to be carried out in Iran, and it was conducted in order to obtain an improved understanding of the disease burden of this virus, particularly with regard to CNS involvement. PATIENTS AND METHODS: Viral RNA was extracted from 170 cerebrospinal fluid samples obtained from children aged under 8 years with a primary diagnosis of aseptic meningitis. Specific EV71 PCR was conducted to identify the genotype of the detected EV71 viruses. RESULTS: Human enteroviruses (HEVs) were detected in 89 patients (52.3%). EV71 infection was detected in 19 (21.3%) of the 89 EV71-positive patients, and the C genotype was identified in 15 isolates. CONCLUSIONS: The C genotype should be considered as the prevalent EV71 circulating genotype in Iran, particularly in cases of aseptic meningitis. PMID- 26865944 TI - Antimicrobial Activity of Lactobacillus spp. Isolated From Fecal Flora of Healthy Breast-Fed Infants Against Diarrheagenic Escherichia coli. AB - BACKGROUND: Among the enteric pathogens, diarrheagenic Escherichia coli are important causes of diarrhea in children in both developing and industrialized countries. Some Lactobacillus species are commonly used as probiotics, with effects especially against acute diarrhea in childhood. OBJECTIVES: The aim of this study was to explore antimicrobial activity of Lactobacillus strains isolated from fecal flora of healthy breast-fed infants against five diarrheagenic E. coli pathotypes such as enteroaggregative E. coli (EAEC), enterohaemorrhagic E. coli (EHEC) enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). MATERIALS AND METHODS: Fecal samples were collected from seven healthy breast-fed infants between 1 to 18 months of age in Tehran city, Iran. Identification of Lactobacillus isolates was performed by biochemical and 16S rRNA gene sequencing methods. An agar well diffusion assay was used for detection of antimicrobial activity of Lactobacillus isolates against five diarrheagenic E. coli pathotypes. RESULTS: A total of 20 Lactobacillus isolates were identified from stool samples. Lactobacillus fermentum was the most frequently isolated strain, followed by L. plantarum and L. rhamnosus. Seven Lactobacillus strains including L. fermentum (four isolates), L. paracasei (one isolate), L. plantarum (one isolate) and L. rhamnosus (one isolate) had a mild inhibitory activity against diarrheagenic E. coli. The mechanism of inhibitory activity of Lactobacillus strains appeared to be due to the production of organic acids or hydrogen peroxide. CONCLUSIONS: Our findings show that Lactobacillus strains with human origin had a mild inhibitory activity against the diarrheagenic E. coli, and these strains may be useful as probiotic candidates in prevention of intestinal infections caused by diarrheagenic E. coli. PMID- 26865945 TI - Reporting phenotypes in mouse models when considering body size as a potential confounder. AB - Genotype-phenotype studies aim to identify causative relationships between genes and phenotypes. The International Mouse Phenotyping Consortium is a high throughput phenotyping program whose goal is to collect phenotype data for a knockout mouse strain of every protein coding gene. The scale of the project requires an automatic analysis pipeline to detect abnormal phenotypes, and disseminate the resulting gene-phenotype annotation data into public resources. A body weight phenotype is a common result of knockout studies. As body weight correlates with many other biological traits, this challenges the interpretation of related gene-phenotype associations. Co-correlation can lead to gene-phenotype associations that are potentially misleading. Here we use statistical modelling to account for body weight as a potential confounder to assess the impact. We find that there is a considerable impact on previously established gene-phenotype associations due to an increase in sensitivity as well as the confounding effect. We investigated the existing ontologies to represent this phenotypic information and we explored ways to ontologically represent the results of the influence of confounders on gene-phenotype associations. With the scale of data being disseminated within the high throughput programs and the range of downstream studies that utilise these data, it is critical to consider how we improve the quality of the disseminated data and provide a robust ontological representation. PMID- 26865946 TI - Interoperability between phenotypes in research and healthcare terminologies- Investigating partial mappings between HPO and SNOMED CT. AB - BACKGROUND: Identifying partial mappings between two terminologies is of special importance when one terminology is finer-grained than the other, as is the case for the Human Phenotype Ontology (HPO), mainly used for research purposes, and SNOMED CT, mainly used in healthcare. OBJECTIVES: To investigate and contrast lexical and logical approaches to deriving partial mappings between HPO and SNOMED CT. METHODS: 1) Lexical approach-We identify modifiers in HPO terms and attempt to map demodified terms to SNOMED CT through UMLS; 2) Logical approach-We leverage subsumption relations in HPO to infer partial mappings to SNOMED CT; 3) Comparison-We analyze the specific contribution of each approach and evaluate the quality of the partial mappings through manual review. RESULTS: There are 7358 HPO concepts with no complete mapping to SNOMED CT. We identified partial mappings lexically for 33% of them and logically for 82%. We identified partial mappings both lexically and logically for 27%. The clinical relevance of the partial mappings (for a cohort selection use case) is 49% for lexical mappings and 67% for logical mappings. CONCLUSIONS: Through complete and partial mappings, 92% of the 10,454 HPO concepts can be mapped to SNOMED CT (30% complete and 62% partial). Equivalence mappings between HPO and SNOMED CT allow for interoperability between data described using these two systems. However, due to differences in focus and granularity, equivalence is only possible for 30% of HPO classes. In the remaining cases, partial mappings provide a next-best approach for traversing between the two systems. Both lexical and logical mapping techniques produce mappings that cannot be generated by the other technique, suggesting that the two techniques are complementary to each other. Finally, this work demonstrates interesting properties (both lexical and logical) of HPO and SNOMED CT and illustrates some limitations of mapping through UMLS. PMID- 26865947 TI - Towards exergaming commons: composing the exergame ontology for publishing open game data. AB - BACKGROUND: It has been shown that exergames have multiple benefits for physical, mental and cognitive health. Only recently, however, researchers have started considering them as health monitoring tools, through collection and analysis of game metrics data. In light of this and initiatives like the Quantified Self, there is an emerging need to open the data produced by health games and their associated metrics in order for them to be evaluated by the research community in an attempt to quantify their potential health, cognitive and physiological benefits. METHODS: We have developed an ontology that describes exergames using the Web Ontology Language (OWL); it is available at http://purl.org/net/exergame/ns#. After an investigation of key components of exergames, relevant ontologies were incorporated, while necessary classes and properties were defined to model these components. A JavaScript framework was also developed in order to apply the ontology to online exergames. Finally, a SPARQL Endpoint is provided to enable open data access to potential clients through the web. RESULTS: Exergame components include details for players, game sessions, as well as, data produced during these game-playing sessions. The description of the game includes elements such as goals, game controllers and presentation hardware used; what is more, concepts from already existing ontologies are reused/repurposed. Game sessions include information related to the player, the date and venue where the game was played, as well as, the results/scores that were produced/achieved. These games are subsequently played by 14 users in multiple game sessions and the results derived from these sessions are published in a triplestore as open data. CONCLUSIONS: We model concepts related to exergames by providing a standardized structure for reference and comparison. This is the first work that publishes data from actual exergame sessions on the web, facilitating the integration and analysis of the data, while allowing open data access through the web in an effort to enable the concept of Open Trials for Active and Healthy Ageing. PMID- 26865948 TI - IspH-RPS1 and IspH-UbiA: "Rosetta Stone" Proteins. AB - The protein IspH, (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMPPP) reductase, is an essential 4Fe-4S cluster-containing protein in the methylerythritol phosphate pathway for isoprenoid biosynthesis. Using a sequence similarity network we found that there are >400 IspH proteins that are about twice as large as most of the IspHs studied to date since their IspH domains are fused to either the ribosomal protein S1 (RPS1), or to a UbiA (4-hydroxybenzoate octaprenyltransferase)-like protein. Many of the IspH-RPS1 proteins are present in anaerobes found in the human gut and some, such as Clostridium botulinum, C. tetani and Fusobacterium nucleatum, are pathogens. The IspH-UbiAs are all found in sulfate-reducing anaerobes. The IspH domains in IspH-RPS1 are fused to 4 and in a few cases 6 tandem repeats in RPS1 that, in most organisms, bind to mRNA or form part of the bacterial ribosome. Mutants in which the four RPS1 domains were sequentially eliminated had similar IspH activity as wild-type protein, indicating they are not essential for IspH catalysis. Overall, the results are of interest since they represent the first isolation of a catalytically active IspH RPS1, as well as the identification of IspH-UbiA hybrids, two "Rosetta stone" proteins that are likely to be functionally related-IspH producing the isoprenoids required for a UbiA-like prenyl transferase; the IspH-RPS1 hybrids, perhaps, being involved in the stringent response or as Fe/O2 sensors. PMID- 26865949 TI - Key influence of sex on urine volume and osmolality. AB - BACKGROUND: Demographics influence kidney stone risk and the type of stone that is more likely to form. Common kidney stone risk factors include having a low urine volume and a high urine concentration. The goal of the current study was to evaluate the effect of demographics on urinary concentration and osmole excretion. METHODS: Twenty-four-hour urine samples were collected from non Hispanic white sibships in Rochester, MN. Height, weight, blood pressure, serum creatinine, and cystatin C were measured. Diet was assessed using the Viocare food frequency questionnaire. Effects of demographics and dietary elements on urine osmolality and volume were evaluated in bivariate and multivariable models, as well as models that included dietary interactions with age, sex, and weight. RESULTS: Samples were available from 709 individuals (mean age 66 +/- 9 years, 59 % female). Across the age spectrum, males had higher urine osmolality (~140 mOsm/kg, p < 0.0001) and total osmole excretion (~270 mOsm, p < 0.0001) compared to females. For any given urine volume, males had a consistently higher urine osmolality (~140 mOsm/kg, p < 0.0001). In multivariable models, urine osmolality declined with age and water intake and remained higher in males than females. Urine osmolality positively associated with weight and animal protein intake. Higher urine volume associated with larger water intake. An interaction revealed that greater body weight was associated with larger changes in urine osmolality as oxalate intake increased (p = 0.04). CONCLUSION: Data from this study support the hypothesis that there are sex differences in thirst and vasopressin action. This trend in urine concentration is also consistent with known epidemiologic patterns of urinary stone disease risk. PMID- 26865950 TI - Erratum to: The burden of smoking in Israel-attributable mortality and costs (2014). AB - [This corrects the article DOI: 10.1186/2045-4015-3-28.]. PMID- 26865951 TI - Different pitcher shapes and trapping syndromes explain resource partitioning in Nepenthes species. AB - Nepenthes pitcher plants display interspecific diversity in pitcher form and diets. This species-rich genus might be a conspicuous candidate for an adaptive radiation. However, the pitcher traits of different species have never been quantified in a comparative study, nor have their possible adaptations to the resources they exploit been tested. In this study, we compare the pitcher features and prey composition of the seven Nepenthes taxa that grow in the heath forest of Brunei (Borneo) and investigate whether these species display different trapping syndromes that target different prey. The Nepenthes species are shown to display species-specific combinations of pitcher shapes, volumes, rewards, attraction and capture traits, and different degrees of ontogenetic pitcher dimorphism. The prey spectra also differ among plant species and between ontogenetic morphotypes in their combinations of ants, flying insects, termites, and noninsect guilds. According to a discriminant analysis, the Nepenthes species collected at the same site differ significantly in prey abundance and composition at the level of order, showing niche segregation but with varying degrees of niche overlap according to pairwise species comparisons. Weakly carnivorous species are first characterized by an absence of attractive traits. Generalist carnivorous species have a sweet odor, a wide pitcher aperture, and an acidic pitcher fluid. Guild specializations are explained by different combinations of morpho-functional traits. Ant captures increase with extrafloral nectar, fluid acidity, and slippery waxy walls. Termite captures increase with narrowness of pitchers, presence of a rim of edible trichomes, and symbiotic association with ants. The abundance of flying insects is primarily correlated with pitcher conicity, pitcher aperture diameter, and odor presence. Such species-specific syndromes favoring resource partitioning may result from local character displacement by competition and/or previous adaptations to geographically distinct environments. PMID- 26865952 TI - Scale dependence of sex ratio in wild plant populations: implications for social selection. AB - Social context refers to the composition of an individual's social interactants, including potential mates. In spatially structured populations, social context can vary among individuals within populations, generating the opportunity for social selection to drive differences in fitness functions among individuals at a fine spatial scale. In sexually polymorphic plants, the local sex ratio varies at a fine scale and thus has the potential to generate this opportunity. We measured the spatial distribution of two wild populations of the gynodioecious plant Silene vulgaris and show that there is fine-scale heterogeneity in the local distribution of the sexes within these populations. We demonstrate that the largest variance in sex ratio is among nearest neighbors. This variance is greatly reduced as the spatial scale of social interactions increases. These patterns suggest the sex of neighbors has the potential to generate fine-scale differences in selection differentials among individuals. One of the most important determinants of social interactions in plants is the behavior of pollinators. These results suggest that the potential for selection arising from sex ratio will be greatest when pollen is shared among nearest neighbors. Future studies incorporating the movement of pollinators may reveal whether and how this fine-scale variance in sex ratio affects the fitness of individuals in these populations. PMID- 26865953 TI - Leaf traits in Chilean matorral: sclerophylly within, among, and beyond matorral, and its environmental determinants. AB - Studies of leaf traits often focus on tradeoffs between growth and resource conservation, but little is known about variation in the mechanical traits that influence resource conservation. This study investigates how leaf mechanical traits vary across matorral vegetation in central Chile, how they correlate with environmental factors, and how these trends compare at a broader geographic scale. Leaf toughness, strength, stiffness, and associated traits were measured in five matorral types in central Chile, and relationships with soil N and P and climate variables were assessed. Trends with soil and climate were then analyzed across shrubland and woodland in Chile, Western Australia, and New Caledonia. Chilean species varied in leaf mechanics and associated traits, both within and among matorral types, with more species in sclerophyll matorral having strong, tough, and stiff leaves than in arid and littoral matorral. Overall, leaves with high leaf dry mass per area were stiffer, tougher, stronger, thicker, denser, with more fiber, lignin, phenolics and fiber per unit protein and less protein: tannin activity and N and P per mass, forming a broad sclerophylly syndrome. Mechanical traits of matorral species were not correlated with soil N or P, or predictably with climate variables, except flexural stiffness (EI W) which correlated positively with annual reference evapotranspiration (ET 0). However, soil P made strong independent contributions to variation in leaf mechanics across shrublands and woodlands of Chile, Western Australia, and New Caledonia, either separately (strength) or together with ET 0 (toughness) explaining 46-90% of variation. Hence ET 0 was predictive of EI W in Chilean matorral, whereas soil P was highly predictive of variation in leaf strength, and combined with ET 0 was highly predictive of toughness, at a broader geographic scale. The biological basis of these relationships, however, may be complex. PMID- 26865954 TI - Timing and location of reproduction in African waterfowl: an overview of >100 years of nest records. AB - The timing and location of reproduction are fundamental elements of reproductive success for all organisms. Understanding why animals choose to reproduce at particular times and in particular places is also important for our understanding of other aspects of organismal ecology, such as their habitat requirements, movement strategies, and biogeography. Although breeding patterns in waterfowl are relatively well documented, most studies are from northern temperate regions and the influences of location and time of year on breeding in Afrotropical ducks (Anatidae) are poorly understood. We outline six alternative (but not mutually exclusive) hypotheses that might explain where and when Afrotropical ducks choose to breed. To explore these hypotheses, we assembled and analyzed a new database of c. 22,000 breeding records for 16 Afrotropical ducks and one introduced Palearctic species (the Mallard Anas platyrhynchos). The full database is available on line as an appendix to this article. We identified five distinct breeding strategies as well as two outliers. Peak breeding for 9 of 16 indigenous duck species occurs during the dry season. We found no evidence for spatial synchrony or spatial autocorrelation in breeding, suggesting a high level of flexibility in waterfowl responses to prevailing conditions in any given year. More intensive analyses of alternative hypotheses are needed, but our initial analysis suggests that the timing of breeding for the majority of Afrotropical ducks is driven by a combination of resource availability and predation risk. PMID- 26865955 TI - Within species support for the expensive tissue hypothesis: a negative association between brain size and visceral fat storage in females of the Pacific seaweed pipefish. AB - The brain is one of the most energetically expensive organs in the vertebrate body. Consequently, the high cost of brain development and maintenance is predicted to constrain adaptive brain size evolution (the expensive tissue hypothesis, ETH). Here, we test the ETH in a teleost fish with predominant female mating competition (reversed sex roles) and male pregnancy, the pacific seaweed pipefish Syngnathus schlegeli. The relative size of the brain and other energetically expensive organs (kidney, liver, heart, gut, visceral fat, and ovary/testis) was compared among three groups: pregnant males, nonpregnant males and egg producing females. Brood size in pregnant males was unrelated to brain size or the size of any other organ, whereas positive relationships were found between ovary size, kidney size, and liver size in females. Moreover, we found that the size of energetically expensive organs (brain, heart, gut, kidney, and liver) as well as the amount of visceral fat did not differ between pregnant and nonpregnant males. However, we found marked differences in relative size of the expensive organs between sexes. Females had larger liver and kidney than males, whereas males stored more visceral fat than females. Furthermore, in females we found a negative correlation between brain size and the amount of visceral fat, whereas in males, a positive trend between brain size and both liver and heart size was found. These results suggest that, while the majority of variation in the size of various expensive organs in this species likely reflects that individuals in good condition can afford to allocate resources to several organs, the cost of the expensive brain was visible in the visceral fat content of females, possibly due to the high costs associated with female egg production. PMID- 26865956 TI - Comparative phylogeography and evolutionary history of schizothoracine fishes in the Changtang Plateau and their implications for the lake level and Pleistocene climate fluctuations. AB - The water level oscillation of endorheic lakes and extent change of glaciers associated with the Asian monsoon are known as prominent representatives of climatic and environmental events in the Tibetan Plateau during the Quaternary. However, details process in spatial and temporal changes are still debated. We use the schizothoracines as a palaeoclimatic proxy to test two hypotheses concerning the evolution of Quaternary glaciations and lakes of the Changtang Plateau: (1) the Tibetan glaciations generally tended to decrease since the middle Pleistocene; (2) the lakes expansion was driven by summer monsoon rainfall. Based on a wide range-wide sampling throughout in the Changtang Plateau and its adjacent drainages, we constructed phylogeny and demographic histories of schizothoracines in the Changtang Plateau. Our results showed that the populations of the exorheic rivers and lakes in southern Tibet possessed higher genetic variability, earlier coalescent and expansion times than those of the endorheic lakes in the Changtang Plateau. Population expansions are highly consistent with phases of strong summer monsoon and high lake level during interglacial stages. The maximum growth rate intervals showed three pulses from 64.7 to 54.8, 39.6 to 31.0, and 14.9 to 2.4 kya respectively. The significant positive correlations were found between regional precipitation and genetic diversity, as well as coalescence time of populations in the endorheic lakes. We suggested that the demographic history of the schizothoracines reflects the spatial and temporal changes in climate and lake level, in particular, in regional precipitation gradients associated with changes of the South Asian monsoon, and supports the climatic hypothesis of a general diminishing tend in Tibetan glaciations in the Tibetan Plateau since the middle Pleistocene. PMID- 26865957 TI - Grazing exclusion reduced soil respiration but increased its temperature sensitivity in a Meadow Grassland on the Tibetan Plateau. AB - Understanding anthropogenic influences on soil respiration (R s) is critical for accurate predictions of soil carbon fluxes, but it is not known how R s responds to grazing exclusion (GE). Here, we conducted a manipulative experiment in a meadow grassland on the Tibetan Plateau to investigate the effects of GE on R s. The exclusion of livestock significantly increased soil moisture and above-ground biomass, but it decreased soil temperature, microbial biomass carbon (MBC), and R s. Regression analysis indicated that the effects of GE on R s were mainly due to changes in soil temperature, soil moisture, and MBC. Compared with the grazed blocks, GE significantly decreased soil carbon release by 23.6% over the growing season and 21.4% annually, but it increased the temperature sensitivity (Q10) of R s by 6.5% and 14.2% for the growing season and annually respectively. Therefore, GE may reduce the release of soil carbon from the Tibetan Plateau, but under future climate warming scenarios, the increases in Q10 induced by GE could lead to increased carbon emissions. PMID- 26865958 TI - Patterns of hybridization among cutthroat trout and rainbow trout in northern Rocky Mountain streams. AB - Introgressive hybridization between native and introduced species is a growing conservation concern. For native cutthroat trout and introduced rainbow trout in western North America, this process is thought to lead to the formation of hybrid swarms and the loss of monophyletic evolutionary lineages. Previous studies of this phenomenon, however, indicated that hybrid swarms were rare except when native and introduced forms of cutthroat trout co-occurred. We used a panel of 86 diagnostic, single nucleotide polymorphisms to evaluate the genetic composition of 3865 fish captured in 188 locations on 129 streams distributed across western Montana and northern Idaho. Although introgression was common and only 37% of the sites were occupied solely by parental westslope cutthroat trout, levels of hybridization were generally low. Of the 188 sites sampled, 73% contained <=5% rainbow trout alleles and 58% had <=1% rainbow trout alleles. Overall, 72% of specimens were nonadmixed westslope cutthroat trout, and an additional 3.5% were nonadmixed rainbow trout. Samples from seven sites met our criteria for hybrid swarms, that is, an absence of nonadmixed individuals and a random distribution of alleles within the sample; most (6/7) were associated with introgression by Yellowstone cutthroat trout. In streams with multiple sites, upstream locations exhibited less introgression than downstream locations. We conclude that although the widespread introduction of nonnative trout within the historical range of westslope cutthroat trout has increased the incidence of introgression, sites containing nonadmixed populations of this taxon are common and broadly distributed. PMID- 26865959 TI - A tough egg to crack: recreational boats as vectors for invasive goby eggs and transdisciplinary management approaches. AB - Non-native invasive species are a major threat to biodiversity, especially in freshwater ecosystems. Freshwater ecosystems are naturally rather isolated from one another. Nonetheless, invasive species often spread rapidly across water sheds. This spread is to a large extent realized by human activities that provide vectors. For example, recreational boats can carry invasive species propagules as "aquatic hitch-hikers" within and across water sheds. We used invasive gobies in Switzerland as a case study to test the plausibility that recreational boats can serve as vectors for invasive fish and that fish eggs can serve as propagules. We found that the peak season of boat movements across Switzerland and the goby spawning season overlap temporally. It is thus plausible that goby eggs attached to boats, anchors, or gear may be transported across watersheds. In experimental trials, we found that goby eggs show resistance to physical removal (90 mN attachment strength of individual eggs) and stay attached if exposed to rapid water flow (2.8 m.s(-1)for 1 h). When exposing the eggs to air, we found that hatching success remained high (>95%) even after eggs had been out of water for up to 24 h. It is thus plausible that eggs survive pick up, within-water and overland transport by boats. We complemented the experimental plausibility tests with a survey on how decision makers from inside and outside academia rate the feasibility of managing recreational boats as vectors. We found consensus that an installation of a preventive boat vector management is considered an effective and urgent measure. This study advances our understanding of the potential of recreational boats to serve as vectors for invasive vertebrate species and demonstrates that preventive management of recreational boats is considered feasible by relevant decision makers inside and outside academia. PMID- 26865961 TI - The use of an unsupervised learning approach for characterizing latent behaviors in accelerometer data. AB - The recent increase in data accuracy from high resolution accelerometers offers substantial potential for improved understanding and prediction of animal movements. However, current approaches used for analysing these multivariable datasets typically require existing knowledge of the behaviors of the animals to inform the behavioral classification process. These methods are thus not well suited for the many cases where limited knowledge of the different behaviors performed exist. Here, we introduce the use of an unsupervised learning algorithm. To illustrate the method's capability we analyse data collected using a combination of GPS and Accelerometers on two seabird species: razorbills (Alca torda) and common guillemots (Uria aalge). We applied the unsupervised learning algorithm Expectation Maximization to characterize latent behavioral states both above and below water at both individual and group level. The application of this flexible approach yielded significant new insights into the foraging strategies of the two study species, both above and below the surface of the water. In addition to general behavioral modes such as flying, floating, as well as descending and ascending phases within the water column, this approach allowed an exploration of previously unstudied and important behaviors such as searching and prey chasing/capture events. We propose that this unsupervised learning approach provides an ideal tool for the systematic analysis of such complex multivariable movement data that are increasingly being obtained with accelerometer tags across species. In particular, we recommend its application in cases where we have limited current knowledge of the behaviors performed and existing supervised learning approaches may have limited utility. PMID- 26865962 TI - Will climate change impact the potential distribution of a native vine (Merremia peltata) which is behaving invasively in the Pacific region? AB - Merremia peltata is a species with uncertain status in the island nations of the Pacific region. It has been designated introduced and invasive in some countries whereas it is considered native in others. Recent increase in its abundance across some island landscapes have led to calls for its designation as an invasive species of environmental concern with biological control being suggested as a control strategy. Climate change will add to the complications of managing this species since changes in climate will influence its range limits. In this study, we develop a process-oriented niche model of M. peltata using CLIMEX to investigate the impacts of climate change on its potential distribution. Information on the climatic requirements of M. peltata and its current geographic distribution were used to calibrate the model. The results indicate that under current climate, 273,132 km(2) of the land area in the region is climatically unsuitable or marginal for M. peltata whereas 664,524 km(2) is suitable to highly suitable. Under current climate, areas of climatic suitability for M. peltata were identified on the archipelagos of Fiji, Papua New Guinea, Solomon Islands and Vanuatu. By the end of the century, some archipelagos like Fiji, Hawaii, New Caledonia and Vanuatu will probably become more suitable while PNG and Solomon Islands become less suitable for M. peltata. The results can be used to inform biosecurity planning, management and conservation strategies on islands. PMID- 26865960 TI - Local parasite lineage sharing in temperate grassland birds provides clues about potential origins of Galapagos avian Plasmodium. AB - Oceanic archipelagos are vulnerable to natural introduction of parasites via migratory birds. Our aim was to characterize the geographic origins of two Plasmodium parasite lineages detected in the Galapagos Islands and in North American breeding bobolinks (Dolichonyx oryzivorus) that regularly stop in Galapagos during migration to their South American overwintering sites. We used samples from a grassland breeding bird assemblage in Nebraska, United States, and parasite DNA sequences from the Galapagos Islands, Ecuador, to compare to global data in a DNA sequence registry. Homologous DNA sequences from parasites detected in bobolinks and more sedentary birds (e.g., brown-headed cowbirds Molothrus ater, and other co-occurring bird species resident on the North American breeding grounds) were compared to those recovered in previous studies from global sites. One parasite lineage that matched between Galapagos birds and the migratory bobolink, Plasmodium lineage B, was the most common lineage detected in the global MalAvi database, matching 49 sequences from unique host/site combinations, 41 of which were of South American origin. We did not detect lineage B in brown headed cowbirds. The other Galapagos-bobolink match, Plasmodium lineage C, was identical to two other sequences from birds sampled in California. We detected a close variant of lineage C in brown-headed cowbirds. Taken together, this pattern suggests that bobolinks became infected with lineage B on the South American end of their migratory range, and with lineage C on the North American breeding grounds. Overall, we detected more parasite lineages in bobolinks than in cowbirds. Galapagos Plasmodium had similar host breadth compared to the non Galapagos haemosporidian lineages detected in bobolinks, brown-headed cowbirds, and other grassland species. This study highlights the utility of global haemosporidian data in the context of migratory bird-parasite connectivity. It is possible that migratory bobolinks bring parasites to the Galapagos and that these parasites originate from different biogeographic regions representing both their breeding and overwintering sites. PMID- 26865963 TI - Fixation probability of rare nonmutator and evolution of mutation rates. AB - Although mutations drive the evolutionary process, the rates at which the mutations occur are themselves subject to evolutionary forces. Our purpose here is to understand the role of selection and random genetic drift in the evolution of mutation rates, and we address this question in asexual populations at mutation-selection equilibrium neglecting selective sweeps. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large asexual population of mutators and find that a nonmutator is more likely to fix when the deleterious mutation rate of the mutator population is high. Compensatory mutations in the mutator population are found to decrease the fixation probability of a nonmutator when the selection coefficient is large. But, surprisingly, the fixation probability changes nonmonotonically with increasing compensatory mutation rate when the selection is mild. Using these results for the fixation probability and a drift-barrier argument, we find a novel relationship between the mutation rates and the population size. We also discuss the time to fix the nonmutator in an adapted population of asexual mutators, and compare our results with experiments. PMID- 26865964 TI - Effects of polyploidy and reproductive mode on life history trait expression. AB - Ploidy elevation is increasingly recognized as a common and important source of genomic variation. Even so, the consequences and biological significance of polyploidy remain unclear, especially in animals. Here, our goal was to identify potential life history costs and benefits of polyploidy by conducting a large multiyear common garden experiment in Potamopyrgus antipodarum, a New Zealand freshwater snail that is a model system for the study of ploidy variation, sexual reproduction, host-parasite coevolution, and invasion ecology. Sexual diploid and asexual triploid and tetraploid P. antipodarum frequently coexist, allowing for powerful direct comparisons across ploidy levels and reproductive modes. Asexual reproduction and polyploidy are very often associated in animals, allowing us to also use these comparisons to address the maintenance of sex, itself one of the most important unresolved questions in evolutionary biology. Our study revealed that sexual diploid P. antipodarum grow and mature substantially more slowly than their asexual polyploid counterparts. We detected a strong negative correlation between the rate of growth and age at reproductive maturity, suggesting that the relatively early maturation of asexual polyploid P. antipodarum is driven by relatively rapid growth. The absence of evidence for life history differences between triploid and tetraploid asexuals indicates that ploidy elevation is unlikely to underlie the differences in trait values that we detected between sexual and asexual snails. Finally, we found that sexual P. antipodarum did not experience discernable phenotypic variance-related benefits of sex and were more likely to die before achieving reproductive maturity than the asexuals. Taken together, these results suggest that under benign conditions, polyploidy does not impose obvious life history costs in P. antipodarum and that sexual P. antipodarum persist despite substantial life history disadvantages relative to their asexual counterparts. PMID- 26865965 TI - Phenotypic plasticity in growth and fecundity induced by strong population fluctuations affects reproductive traits of female fish. AB - Fish are known for their high phenotypic plasticity in life-history traits in relation to environmental variability, and this is particularly pronounced among salmonids in the Northern Hemisphere. Resource limitation leads to trade-offs in phenotypic plasticity between life-history traits related to the reproduction, growth, and survival of individual fish, which have consequences for the age and size distributions of populations, as well as their dynamics and productivity. We studied the effect of plasticity in growth and fecundity of vendace females on their reproductive traits using a series of long-term incubation experiments. The wild parental fish originated from four separate populations with markedly different densities, and hence naturally induced differences in their growth and fecundity. The energy allocation to somatic tissues and eggs prior to spawning served as a proxy for total resource availability to individual females, and its effects on offspring survival and growth were analyzed. Vendace females allocated a rather constant proportion of available energy to eggs (per body mass) despite different growth patterns depending on the total resources in the different lakes; investment into eggs thus dictated the share remaining for growth. The energy allocation to eggs per mass was higher in young than in old spawners and the egg size and the relative fecundity differed between them: Young females produced more and smaller eggs and larvae than old spawners. In contrast to earlier observations of salmonids, a shortage of maternal food resources did not increase offspring size and survival. Vendace females in sparse populations with ample resources and high growth produced larger eggs and larvae. Vendace accommodate strong population fluctuations by their high plasticity in growth and fecundity, which affect their offspring size and consequently their recruitment and productivity, and account for their persistence and resilience in the face of high fishing mortality. PMID- 26865966 TI - Phantoms of the forest: legacy risk effects of a regionally extinct large carnivore. AB - The increased abundance of large carnivores in Europe is a conservation success, but the impact on the behavior and population dynamics of prey species is generally unknown. In Europe, the recolonization of large carnivores often occurs in areas where humans have greatly modified the landscape through forestry or agriculture. Currently, we poorly understand the effects of recolonizing large carnivores on extant prey species in anthropogenic landscapes. Here, we investigated if ungulate prey species showed innate responses to the scent of a regionally exterminated but native large carnivore, and whether the responses were affected by human-induced habitat openness. We experimentally introduced brown bear Ursus arctos scent to artificial feeding sites and used camera traps to document the responses of three sympatric ungulate species. In addition to controls without scent, reindeer scent Rangifer tarandus was used as a noncarnivore, novel control scent. Fallow deer Dama dama strongly avoided areas with bear scent. In the presence of bear scent, all ungulate species generally used open sites more than closed sites, whereas the opposite was observed at sites with reindeer scent or without scent. The opening of forest habitat by human practices, such as forestry and agriculture, creates a larger gradient in habitat openness than available in relatively unaffected closed forest systems, which may create opportunities for prey to alter their habitat selection and reduce predation risk in human-modified systems that do not exist in more natural forest systems. Increased knowledge about antipredator responses in areas subjected to anthropogenic change is important because these responses may affect prey population dynamics, lower trophic levels, and attitudes toward large carnivores. These aspects may be of particular relevance in the light of the increasing wildlife populations across much of Europe. PMID- 26865967 TI - Photographic identification of individuals of a free-ranging, small terrestrial vertebrate. AB - Recognition of individuals within an animal population is central to a range of estimates about population structure and dynamics. However, traditional methods of distinguishing individuals, by some form of physical marking, often rely on capture and handling which may affect aspects of normal behavior. Photographic identification has been used as a less-invasive alternative, but limitations in both manual and computer-automated recognition of individuals are particularly problematic for smaller taxa (<500 g). In this study, we explored the use of photographic identification for individuals of a free-ranging, small terrestrial reptile using (a) independent observers, and (b) automated matching with the Interactive Individual Identification System (I(3)S Pattern) computer algorithm. We tested the technique on individuals of an Australian skink in the Egernia group, Slater's skink Liopholis slateri, whose natural history and varied scale markings make it a potentially suitable candidate for photo-identification. From 'photographic captures' of skink head profiles, we designed a multi-choice key based on alternate character states and tested the abilities of observers - with or without experience in wildlife survey - to identify individuals using categorized test photos. We also used the I(3)S Pattern algorithm to match the same set of test photos against a database of 30 individuals. Experienced observers identified a significantly higher proportion of photos correctly (74%) than those with no experience (63%) while the I(3)S software correctly matched 67% as the first ranked match and 83% of images in the top five ranks. This study is one of the first to investigate photo identification with a free-ranging small vertebrate. The method demonstrated here has the potential to be applied to the developing field of camera-traps for wildlife survey and thus a wide range of survey and monitoring applications. PMID- 26865968 TI - Conservation genetics in Chinese sheep: diversity of fourteen indigenous sheep (Ovis aries) using microsatellite markers. AB - The domestic sheep (Ovis aries) has been an economically and culturally important farm animal species since its domestication around the world. A wide array of sheep breeds with abundant phenotypic diversity exists including domestication and selection as well as the indigenous breeds may harbor specific features as a result of adaptation to their environment. The objective of this study was to investigate the population structure of indigenous sheep in a large geographic location of the Chinese mainland. Six microsatellites were genotyped for 611 individuals from 14 populations. The mean number of alleles (+/-SD) ranged from 7.00 +/- 3.69 in Gangba sheep to 10.50 +/- 4.23 in Tibetan sheep. The observed heterozygote frequency (+/-SD) within a population ranged from 0.58 +/- 0.03 in Gangba sheep to 0.71 +/- 0.03 in Zazakh sheep and Minxian black fur sheep. In addition, there was a low pairwise difference among the Minxian black fur sheep, Mongolian sheep, Gansu alpine merino, and Lanzhou fat-tailed sheep. Bayesian analysis with the program STRUCTURE showed support for 3 clusters, revealing a vague genetic clustering pattern with geographic location. The results of the current study inferred high genetic diversity within these native sheep in the Chinese mainland. PMID- 26865969 TI - Stress-induced changes in abundance differ among obligate and facultative endosymbionts of the soybean aphid. AB - Bacterial endosymbionts can drive evolutionary novelty by conferring adaptive benefits under adverse environmental conditions. Among aphid species there is growing evidence that symbionts influence tolerance to various forms of stress. However, the extent to which stress inflicted on the aphid host has cascading effects on symbiont community dynamics remains poorly understood. Here we simultaneously quantified the effect of host-plant induced and xenobiotic stress on soybean aphid (Aphis glycines) fitness and relative abundance of its three bacterial symbionts. Exposure to soybean defensive stress (Rag1 gene) and a neurotoxic insecticide (thiamethoxam) substantially reduced aphid composite fitness (survival * reproduction) by 74 +/- 10% and 92 +/- 2%, respectively, which in turn induced distinctive changes in the endosymbiont microbiota. When challenged by host-plant defenses a 1.4-fold reduction in abundance of the obligate symbiont Buchnera was observed across four aphid clonal lines. Among facultative symbionts of Rag1-stressed aphids, Wolbachia abundance increased twofold and Arsenophonus decreased 1.5-fold. A similar pattern was observed under xenobiotic stress, with Buchnera and Arsenophonus titers decreasing (1.3-fold) and Wolbachia increasing (1.5-fold). Furthermore, variation in aphid virulence to Rag1 was positively correlated with changes in Arsenophonus titers, but not Wolbachia or Buchnera. A single Arsenophonus multi-locus genotype was found among aphid clonal lines, indicating strain diversity is not primarily responsible for correlated host-symbiont stress levels. Overall, our results demonstrate the nature of aphid symbioses can significantly affect the outcome of interactions under stress and suggests general changes in the microbiome can occur across multiple stress types. PMID- 26865970 TI - Condition dependence of male and female reproductive success: insights from a simultaneous hermaphrodite. AB - Sexually selected traits are predicted to show condition dependence by capturing the genetic quality of its bearer. In separate-sexed organisms, this will ultimately translate into condition dependence of reproductive success of the sex that experiences sexual selection, which is typically the male. Such condition dependence of reproductive success is predicted to be higher in males than females under conditions promoting intense sexual selection. For simultaneous hermaphrodites, however, sex allocation theory predicts that individuals in poor condition channel relatively more resources into the male sex function at the expense of the female function. Thus, male reproductive success is expected to be less condition dependent than female reproductive success. We subjected individuals of the simultaneously hermaphroditic snail Physa acuta to two feeding treatments to test for condition dependence of male and female reproductive success under varying levels of male-male competition. Condition dependence was found for female, but not for male, reproductive success, meaning that selection on condition is relatively stronger through the female sex function. This effect was consistent over both male-male competition treatments. Decomposition of male and female reproductive performance revealed that individuals in poor condition copulated more in their male role, indicating an increased male allocation to mate acquisition. These findings suggest that sex-specific condition dependence of reproductive success is at least partially driven by condition-dependent sex allocation. We discuss the implications of condition-dependent sex allocation for the evolution of sexually selected traits in simultaneous hermaphrodites. PMID- 26865972 TI - Evolution of tail fork depth in genus Hirundo. AB - A classic example of a sexually selected trait, the deep fork tail of the barn swallow Hirundo rustica is now claimed to have evolved and be maintained mainly via aerodynamic advantage rather than sexually selected advantage. However, this aerodynamic advantage hypothesis does not clarify which flight habits select for/against deep fork tails, causing diversity of tail fork depth in hirundines. Here, by focusing on the genus Hirundo, we investigated whether the large variation in tail fork depth could be explained by the differential flight habits. Using a phylogenetic comparative approach, we found that migrant species had deeper fork tails, but less colorful plumage, than the other species, indicating that migration favors a specific trait, deep fork tails. At the same time, tail fork depth but not plumage coloration decreased with increasing bill size - a proxy of prey size, suggesting that foraging on larger prey items favors shallower fork tails. Variation of tail fork depth in the genus Hirundo may be explained by differential flight habits, even without assuming sexual selection. PMID- 26865971 TI - Tree species richness decreases while species evenness increases with disturbance frequency in a natural boreal forest landscape. AB - Understanding species diversity and disturbance relationships is important for biodiversity conservation in disturbance-driven boreal forests. Species richness and evenness may respond differently with stand development following fire. Furthermore, few studies have simultaneously accounted for the influences of climate and local site conditions on species diversity. Using forest inventory data, we examined the relationships between species richness, Shannon's index, evenness, and time since last stand-replacing fire (TSF) in a large landscape of disturbance-driven boreal forest. TSF has negative effect on species richness and Shannon's index, and a positive effect on species evenness. Path analysis revealed that the environmental variables affect richness and Shannon's index only through their effects on TSF while affecting evenness directly as well as through their effects on TSF. Synthesis and applications. Our results demonstrate that species richness and Shannon's index decrease while species evenness increases with TSF in a boreal forest landscape. Furthermore, we show that disturbance frequency, local site conditions, and climate simultaneously influence tree species diversity through complex direct and indirect effects in the studied boreal forest. PMID- 26865973 TI - Influence of arbuscular mycorrhizal colonization on whole-plant respiration and thermal acclimation of tropical tree seedlings. AB - Symbiotic arbuscular mycorrhizal fungi (AMF) are ubiquitous in tropical forests. AMF play a role in the forest carbon cycle because they can increase nutrient acquisition and biomass of host plants, but also incur a carbon cost to the plant. Through their interactions with their host plants they have the potential to affect how plants respond to environmental perturbation such as global warming. Our objective was to experimentally determine how plant respiration rates and responses to warmer environment are affected by AMF colonization in seedlings of five tropical tree species at the whole plant level. We evaluated the interaction between AMF colonization and temperature on plant respiration against four possible outcomes; acclimation does or does not occur regardless of AMF, or AMF can increase or decrease respiratory acclimation. Seedlings were inoculated with AMF spores or sterilized inoculum and grown at ambient or elevated nighttime temperature. We measured whole plant and belowground respiration rates, as well as plant growth and biomass allocation. There was an overall increase in whole plant, root, and shoot respiration rate with AMF colonization, whereas temperature acclimation varied among species, showing support for three of the four possible responses. The influence of AMF colonization on growth and allocation also varied among plant species. This study shows that the effect of AMF colonization on acclimation differs among plant species. Given the cosmopolitan nature of AMF and the importance of plant acclimation for predicting climate feedbacks a better understanding of the patterns and mechanisms of acclimation is essential for improving predictions of how climate warming may influence vegetation feedbacks. PMID- 26865974 TI - Whole genome sequence analysis of BT-474 using complete Genomics' standard and long fragment read technologies. AB - BACKGROUND: The cell line BT-474 is a popular cell line for studying the biology of cancer and developing novel drugs. However, there is no complete, published genome sequence for this highly utilized scientific resource. In this study we sought to provide a comprehensive and useful data set for the scientific community by generating a whole genome sequence for BT-474. FINDINGS: Five MUg of genomic DNA, isolated from an early passage of the BT-474 cell line, was used to generate a whole genome sequence (114X coverage) using Complete Genomics' standard sequencing process. To provide additional variant phasing and structural variation data we also processed and analyzed two separate libraries of 5 and 6 individual cells to depths of 99X and 87X, respectively, using Complete Genomics' Long Fragment Read (LFR) technology. CONCLUSIONS: BT-474 is a highly aneuploid cell line with an extremely complex genome sequence. This ~300X total coverage genome sequence provides a more complete understanding of this highly utilized cell line at the genomic level. PMID- 26865975 TI - Antimicrobial susceptibility and molecular epidemiology of extended-spectrum beta lactamase-producing Enterobacteriaceae from intensive care units at Hamad Medical Corporation, Qatar. AB - BACKGROUND: The emergence of extended-spectrum beta-lactamase (ESBL)-producing isolates has important clinical and therapeutic implications. High prevalence of ESBL-producing Enterobacteriaceae has been reported in the literature for clinical samples from a variety of infection sites. The present study was undertaken to evaluate the prevalence of ESBL-producing Enterobacteriaceae, and to perform molecular characterization and antimicrobial susceptibility testing of clinical isolates from patients admitted to the intensive care units at Hamad Medical Corporation, Doha, Qatar, from November 2012 to October 2013. METHODS: A total of 629 Enterobacteriaceae isolates were included in the study. Identification and susceptibility testing was performed using Phoenix (Becton Dickinson) and the ESBL producers were confirmed by double-disk potentiation as recommended by the Clinical and Laboratory Standards Institute. Molecular analysis of the ESBL producers was performed by polymerase chain reaction. RESULTS: In total, 109 isolates (17.3 %) were confirmed as ESBL producers and all were sensitive to meropenem in routine susceptibility assays. Most of the ESBL producers (99.1 %) were resistant to amoxicillin/clavulanic acid and ceftriaxone and 93.6 % were resistant to cefepime. Among the ESBL-producing genes, bla CTX-M (66.1 %) was the most prevalent, followed by bla SHV (53.2 %) and bla TEM (40.4 %). CONCLUSIONS: These findings show the high prevalence of ESBL-producing Enterobacteriaceae within the intensive care units at Hamad Medical Corporation, Qatar, and emphasize the need for judicious use of antibiotics and the implementation of strict infection control measures. PMID- 26865976 TI - Observed outcomes on the use of oxidized and regenerated cellulose polymer for breast conserving surgery - A case series. AB - BACKGROUND: Oxidized regenerated cellulose polymer (ORCP) may be used for reshaping and filling lack of volume in breast-conserving surgery (BCS). The study aimed to observe both the aesthetic and diagnostic outcomes in patients with different age, BMI, breast volume, and breast tissue composition over 36 months after BCS with ORCP. PATIENTS AND METHODS: 18 patients with early breast cancer and with proliferative benign lesions underwent BCS with ORCP that was layered in three-dimensional wafer, and placed into the Chassaignac space between the mammary gland and the fascia of pectoralis major with no fixation. After surgery, patients started a clinical and instrumental 36-month follow-up with mammography, ultrasonography, magnetic resonance imaging (MRI) and cytological examination with fine needle aspiration when seroma occurred. RESULTS: Below the median age of 66 years old no complications were observed even in case both of overweight, and large breasts with low density. Over the median age seromas occurred with either small or large skin retraction, with the exception of 1 patient having quite dense breasts and low BMI, which had no complications. In elderly patients, 1 case with quite dense breasts and high BMI showed severe seroma and skin retraction, while 1 case with low BMI and less dense breasts highlighted milder complications. CONCLUSION: During 36 months after BCS with ORCP, a significant correlation between positive diagnostic and aesthetic outcomes and low age, dense breasts, and low BMI of patient was observed. Despite of the few number of cases, either low BMI, or high breast density improved the aesthetic outcomes and reduced the entity of complications even in the elderly patients. PMID- 26865977 TI - Corneal oedema after phacoemulsification in the early postoperative period: A qualitative comparative case-control study between diabetics and non-diabetics. AB - BACKGROUND: The occurrence and severity of corneal oedema after phacoemulsification is dependent on the integrity of corneal endothelial cells. The function of these cells is affected by diabetes mellitus and consequently the behaviour of the cornea in diabetic patients is of special interest. AIM: To compare the frequency of corneal oedema in two age-matched groups of diabetics and non diabetic patients that underwent cataract surgery in the Ophthalmology Department of Xanthi General Hospital in Greece. METHODS: A retrospective case control study was conducted in a retrospective fashion. Patients in the control and study groups were assessed regarding the severity of corneal oedema at three postoperative visits: days 1, 3-7, 10-14 after the operation. Ultrasound energy consumed during phacoemulsification was also a parameter of interest and possible correlations with the pre-existent cataract severity and the subsequent incidence of corneal oedema were investigated. RESULTS: The difference in the incidence of severe corneal oedema between the study and control group was statistically significant: (4.5% non diabetics vs 14.3% diabetics). The consumed ultrasound energy did not define final clinical outcome. CONCLUSIONS: The existence of diabetes mellitus type 2 appears to be a significant risk factor for the development of persistent corneal oedema. The results of our study led to the modification of the algorithm for postoperative follow-up of patients of this remote area of Greece. PMID- 26865978 TI - Bochdalek hernia: A rare case report of adult age. AB - INTRODUCTION: Bochdalek hernia is the most common type of congenital diaphragmatic hernia and constitutes 85% of cases. Bochdalek hernia (BH) in adults is extremely rare. We present a BH case in an adult patient and discuss the literature. PRESENTATION: 22-year-old female patient with abdominal pain, occasional cramps, dysphagic problems, constipation, shortness of breath and choking for about 2 years applied to our clinic. DIAGNOSIS: A defect about 5 cm in the left hemidiaphragm posterior area and herniation of intra-abdominal fat plan in the left hemithorax was seen in intravenous and oral whole abdominal CT. TREATMENT: Patient was operated laparoscopically. Transverse colon and a large portion of the omentum entering into hemidiaphragm were pulled in to intraperitoneal area carefully. Approximately 10 * 8 cm intraabdominal mesh was fixed to the defect area with the help of laparoscopic tacker. CONCLUSION: Adult BH is very rare and when confronted laparoscopic treatment with mesh fixation can be performed safely. PMID- 26865979 TI - Acceptability and preference of three inhalation devices assessed by the Handling Questionnaire in asthma and COPD patients. AB - BACKGROUND: The patients' criteria of preference for inhalation devices can affect the extent of their adherence to treatment and outcomes. Aim of this study was to assess and compare the patients' preference and acceptability (PPA) for Breezhaler and Genuair (both Dry Powder Inhalers), and for Respimat (a Soft Mist Inhaler) in asthma and COPD out-patients by means of the Handling Questionnaire. METHODS: The Handling Questionnaire is a validated instrument which allows the investigation of different domains of PPA; it also takes into account the patients' age and gender, together with their previous experience with the inhalation devices and their previous education approach to them. Differences in terms of preference, acceptance and usability were assessed by linear and logistic regressions in order to evaluate factors influencing the proper actuation. RESULTS AND DISCUSSION: Data from 333 patients were collected: Genuair and Respimat were the most liked and perceived as the easiest to use at glance by patients, but also as the least problematic according to the patients' and nurse's judgments. Mean number of attempts for achieving the first effective actuation was the highest with Breezhaler (2.6 vs 1.6; p <0.0001). Linear regressions showed that longer the explanation, higher was the number of attempts to the first proper actuation (0.58 additional attempts every 10 s increase in the first explanation, p <0.0001). Devices requiring less manoeuvres for the actuation were used properly after less attempts (0.38 increase in the number of attempts every additional manoeuvres, p <0.0001). Respimat proved to be the most indicated in COPD patients since it was the most liked and its successful rate at first attempt was the highest. Logistic regressions confirmed these data. Previous experience with DPIs and/or MDIs did not affect the patient preference and acceptability, independently whether suffering from asthma or COPD. CONCLUSIONS: Substantial differences are existing in patient's preference and acceptability for inhalation devices, mainly related to the handling and the understanding of the different devices. PMID- 26865980 TI - Process evaluation of the MOSAIC trial: treatment experience of two psychological therapies for out-patient treatment of Anorexia Nervosa. AB - BACKGROUND: This study is part of a series of process evaluations within the MOSAIC Trial (Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions). This randomised controlled trial (RCT) compared two psychological treatments, the Maudsley Model for Treatment of Adults with Anorexia Nervosa (MANTRA) and Specialist Supportive Clinical Management (SSCM) for adult outpatients with Anorexia Nervosa. The present process study integrates quantitative (treatment acceptability and credibility) and qualitative (written) feedback to evaluate patients' treatment experiences. METHOD: All 142 MOSAIC participants were asked to (a) rate treatment acceptability and credibility on visual analogue scales (VAS) at six and 12 months post-randomisation, and (b) provide written feedback regarding their views on their treatment at 12 months. Transcripts were first analysed thematically and then rated according to the global valence of feedback (positive, mixed/negative). RESULTS: 114/142 (80.3 %) MOSAIC participants provided VAS data and 82 (57.7 %) provided written feedback. At 12 months, MANTRA patients gave significantly higher acceptability and credibility ratings compared to SSCM patients. A significantly higher proportion of MANTRA patients provided written feedback. MANTRA patients also tended to write in more detail and to give globally more positive feedback when compared to individuals receiving SSCM. Qualitative themes suggest that patients experienced the two treatments differently in terms of characteristics and outcomes. CONCLUSIONS: This study highlights the benefits of incorporating qualitative and quantitative data into RCT process evaluations. MANTRA patients were more willing to express their views on treatment and generally felt more positively about this than those receiving SSCM. PMID- 26865981 TI - Use of a modified early warning score system to reduce the rate of in-hospital cardiac arrest. AB - BACKGROUND: Physiological abnormalities are often observed in patients prior to cardiac arrest. A modified early warning score (MEWS) system was introduced, which aims to detect early abnormalities by grading vital signs, and the present study investigated its usefulness. METHODS: Based on previous reports, the Chubu Tokushukai Hospital-customized MEWS was developed in Okinawa, Japan. The MEWS was calculated among all inpatients, and the rates of in-hospital cardiac arrests (IHCAs) were compared according to the score. The warning zone (WZ) was set as 7 or more because of the high possibility of acute deterioration. The MEWS system was introduced to provide immediate interventions for patients who reached the WZ in accordance with the callout algorithm. The numbers of IHCAs were compared between the 18 months before and after introduction of the MEWS system. RESULTS: The numbers of patients who experienced IHCA with each score were as follows: score of 6, 1 of 556 patients (0.18 %); score of 7, 4 of 289 (1.40 %); score of 8, 2 of 114 (1.75 %); and score of 9 or more, 2 of 56 (3.57 %). There was no significant difference in the mean age or sex between before and after the introduction of the MEWS system. The rate of IHCAs per 1000 admissions decreased significantly from 5.21 (79/15,170) to 2.05 (43/17,961) (p < 0.01). CONCLUSIONS: The Chubu Tokushukai Hospital-customized MEWS was applied to all inpatients, and the rate of IHCA decreased owing to the introduction of the system, as the system enables early interventions for patients who have the possibility of acute deterioration. PMID- 26865983 TI - Identification of emergent bla CMY-2 -carrying Proteus mirabilis lineages by whole-genome sequencing. AB - Whole-genome sequencing of 24 Proteus mirabilis isolates revealed the clonal expansion of two cefoxitin-resistant strains among patients with community-onset infection. These strains harboured bla CMY-2 within a chromosomally located integrative and conjugative element and exhibited multidrug resistance phenotypes. A predominant strain, identified in 18 patients, also harboured the PGI-1 genomic island and associated resistance genes, accounting for its broader antibiotic resistance profile. The identification of these novel multidrug resistant strains among community-onset infections suggests that they are endemic to this region and represent emergent P. mirabilis lineages of clinical significance. PMID- 26865982 TI - Hypersplenism in liver disease and SLE revisited: current evidence supports an active rather than passive process. AB - BACKGROUND: Active and passive theories have been advanced to explain splenomegaly and cytopenias in liver disease. Dameshek proposed active downregulation of hematopoiesis. Doan proposed passive trapping of blood components in a spleen enlarged by portal hypertension. Recent findings do not support a passive process. DISCUSSION: Cytopenias and splenomegaly in both liver disease and systemic lupus erythematosus (SLE) poorly correlate with portal hypertension, and likely reflect an active process allocating stem cell resources in response to injury. Organ injury is repaired partly by bone-marrow-derived stem cells. Signaling would thus be needed to allocate resources between repair and routine marrow activities, hematologic and bone production. Granulocyte colony stimulating factor (G-CSF) may play a central role: mobilizing stem cells, increasing spleen size and downregulating bone production. Serum G-CSF rises with liver injury, and is elevated in chronic liver disease and SLE. Signaling, not sequestration, likely accounts for splenomegaly and osteopenia in liver disease and SLE. The downregulation of a non-repair use of stem cells, bone production, suggests that repair efforts are prioritized. Other non-repair uses might be downregulated, namely hematologic production, as Dameshek proposed. SUMMARY: Recognition that an active process may exist to allocate stem-cell resources would provide new approaches to diagnosis and treatment of cytopenias in liver disease, SLE and potentially other illnesses. PMID- 26865984 TI - Assessment of drug content uniformity of atropine sulfate triturate by liquid chromatography-tandem mass spectrometry, X-ray powder diffraction, and Raman chemical imaging. AB - BACKGROUND: Atropine sulfate is an anticholinergic agent for treatment of hypertrophic pyloric stenosis and is orally administrated as a triturate with lactose hydrate. Because of the low safety margin of atropine sulfate, triturate uniformity is a key safety factor. In this study, we assessed the uniformity of atropine sulfate in 1000-fold triturates prepared by wet mixing and dry mixing methods and discussed the cause of the difference in uniformity between two preparation methods. METHODS: A 1000-fold triturate of atropine sulfate with lactose hydrate was prepared by two different methods: wet mixing and dry mixing. The wet mixing was performed according to Kurashiki Central Hospital protocol and the dry mixing was a simple physical mixing by a rocking mixer. The uniformity of atropine sulfate content in aliquots of a 1000-fold triturate with lactate hydrate was assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification. Solid-state analyses of the triturates by Raman chemical imaging and X-ray powder diffraction (XRPD) were performed to investigate the difference in uniformity. RESULTS: The LC-MS/MS quantification showed that the uniformity of atropine sulfate in the 1000-fold triturate was excellent for wet mixing but was significantly variable for dry mixing. On the basis of the Raman chemical imaging and XRPD analyses, it was indicated that an amorphous thin film of atropine sulfate coated the surfaces of the lactose hydrate particles during wet mixing and contributed to the uniformity of the triturate. In contrast, clusters of the crystalline atropine sulfate were found in the dry mixing samples. CONCLUSION: The results showed that better atropine sulfate triturate uniformity was achieved using the wet mixing method rather than the dry method and the cause of the uniformity difference between two mixing methods was indicated by the multilateral assessment. PMID- 26865985 TI - Electrophoretically prepared hybrid materials for biopolymer hydrogel and layered ceramic nanoparticles. AB - BACKGROUND: In order to obtain biomaterials with controllable physicochemical properties, hybrid biomaterials composed of biocompatible biopolymers and ceramic nanoparticles have attracted interests. In this study, we prepared biopolymer/ceramic hybrids consisting of various natural biopolymers and layered double hydroxide (LDH) ceramic nanoparticles via an electrophoretic method. We studied the structures and controlled-release properties of these materials. RESULTS AND DISCUSSION: X-ray diffraction (XRD) patterns and X-ray absorption spectra (XAS) showed that LDH nanoparticles were formed in a biopolymer hydrogel through electrophoretic reaction. Scanning electron microscopic (SEM) images showed that the ceramic nanoparticles were homogeneously distributed throughout the hydrogel matrix. An antioxidant agent (i.e., ferulic acid) was loaded onto agarose/LDH and gelatin/LDH hybrids, and the time-dependent release of ferulic acid was investigated via high-performance liquid chromatography (HPLC) for kinetic model fitting. CONCLUSIONS: Biopolymer/LDH hybrid materials that were prepared by electrophoretic method created a homogeneous composite of two components and possessed controllable drug release properties according to the type of biopolymer. PMID- 26865986 TI - Evidence for Placental HPV Infection in Both HIV Positive and Negative Women. AB - Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV- groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV- (p = 0.0241). HPV16 L1 expression, detected by immunochemistry, was significantly higher in HIV+ than HIV- samples (p = 0.0231). HPV16 DNA was detected in the nuclei of trophoblast cells by in situ hybridization. Overall, these results suggest that HPVs infect the placenta and that HIV significantly influences these infections. PMID- 26865987 TI - Historical Parallels, Ebola Virus Disease and Cholera: Understanding Community Distrust and Social Violence with Epidemics. AB - In the three West African countries most affected by the recent Ebola virus disease (EVD) outbreak, resistance to public health measures contributed to the startling speed and persistence of this epidemic in the region. But how do we explain this resistance, and how have people in these communities understood their actions? By comparing these recent events to historical precedents during Cholera outbreaks in Europe in the 19th century we show that these events have not been new to history or unique to Africa. Community resistance must be analysed in context and go beyond simple single-variable determinants. Knowledge and respect of the cultures and beliefs of the afflicted is essential for dealing with threatening disease outbreaks and their potential social violence. PMID- 26865989 TI - Evacuation During Hurricane Sandy: Data from a Rapid Community Assessment. AB - INTRODUCTION: In anticipation of Hurricane Sandy in 2012 New York City officials issued mandatory evacuation orders for evacuation Zone A. However, only a small proportion of residents complied. Failure to comply with evacuation warnings can result in severe consequences including injury and death. To better ascertain why individuals failed to heed pre--emptive evacuation warnings for Hurricane Sandy we assessed factors that may have affected evacuation among residents in neighborhoods severely affected by the storm. METHODS: Data from a mental health needs assessment survey conducted among adult residents in South Brooklyn, the Rockaways, and Staten Island from December 13--18, 2012 was assessed. Several disasters related questions were evaluated, and prevalence estimates of evacuation and evacuation timing by potential factors that may influence evacuation were estimated. Measures of association were assessed using chi- square and t--test. RESULTS: Our sample consisted of 420 residents of which, only 49% evacuated at any time for Sandy. Evacuation was higher among those who witnessed trauma to others related to the World Trade Center attacks (66% vs. 40%, p=0.024). Those who reported extensive household damage after Sandy, had a higher rate of evacuation than those with minimal damage (83% vs. 30%, p<0.001). Among those who evacuated, evacuation before the storm was lower among residents living on higher floors (56% vs. 22%, p=0.022). DISCUSSION: Given that warnings to evacuate were issued before Sandy made landfall, evacuation among residents in South Brooklyn, the Rockaways and Staten Island, while higher than the overall Zone A evacuation rate, was less than optimal. Continued research on evacuation behaviors is needed, particularly on how timing affects evacuation. A better understanding may help to reduce barriers, and improve evacuation compliance. PMID- 26865988 TI - Immediate Needs and Concerns among Pregnant Women During and after Typhoon Haiyan (Yolanda). AB - INTRODUCTION: Pregnant and postpartum women are especially vulnerable to natural disasters. These women suffer from increased risk of physical and mental issues including pregnant related problems. Typhoon Haiyan (Yolanda), which hit the Philippines affected a large number of people and caused devastating damages. During and after the typhoon, pregnant women were forced to live in particularly difficult circumstances. The purpose of this study was to determine concerns and problems regarding public health needs and coping mechanisms among pregnant women during and shortly after the typhoon. METHODS: This study employed a cross sectional design utilizing focus group discussions (FGDs). Participants were 53 women (mean age: 26.6 years old; 42 had children) from four affected communities who were pregnant at the time of the typhoon. FGDs were conducted 4 months after the typhoon, from March 19 to 28, 2014, using semi-structured interviews. Data were analyzed using the qualitative content analysis. RESULT: Three themes were identified regarding problems and concerns during and after the typhoon: 1) having no ideas what is going to happen during the evacuation, 2) lacking essentials to survive, and 3) being unsure of how to deal with health concerns. Two themes were identified as means of solving issues: 1) finding food for survival and 2) avoiding diseases to save my family. As the pregnant women already had several typhoon experiences without any major problems, they underestimated the catastrophic nature of this typhoon. During the typhoon, the women could not ensure their safety and did not have a strong sense of crisis management. They suffered from hunger, food shortage, and poor sanitation. Moreover, though the women had fear and anxiety regarding their pregnancy, they had no way to resolve these concerns. Pregnant women and their families also suffered from common health problems for which they would usually seek medical services. Under such conditions, the pregnant woman cooperated with others for survival and used their knowledge of disease prevention. DISCUSSION: Pregnant women experienced difficulties with evacuation, a lack of minimum survival needs, and attending to their own health issues. Pregnant women were also concerned about needs and health issues of their families, particular, when they had small children. Collecting accurate information regarding the disaster and conducting self-sustainable preparation prior to the disaster among pregnant women will help them to protect their pregnancy status, thereby improving their families' chance of survival during and after disasters. PMID- 26865990 TI - Methods for an International Randomized Clinical Trial to Investigate the Effect of Gsk249320 on Motor Cortex Neurophysiology using Transcranial Magnetic Stimulation in Survivors of Stroke. AB - INTRODUCTION: Transcranial Magnetic Stimulation (TMS) is a neurophysiological tool capable of assessing the motor nervous system and its change over time. In multi-site clinical trials, this technique has some advantages over other neuroimaging methods owing to its relatively low cost, low personnel and equipment infrastructure requirements, and greater ease in consistently applying technology to collect and analyze data. Limited published details exist regarding methods to deliver TMS and analyze data in a standardized and consistent manner as part of an international, multicenter, clinical trial. PURPOSE: The objective of this paper is to describe standardized methods of applying TMS motor cortex assessments in an international clinical trial of a pharmacological intervention for stroke patients, which was conducted at 15 centers in three countries. MATERIALS AND METHODS: A standardization process was developed to ensure TMS protocol adherence and data quality, and each clinical site was required to successfully complete standardization procedures prior to collecting patient data. Key elements of standardization included internet-based training, pilot subject data collection, common TMS equipment across sites, and corrective feedback provided by a standardization administrator. Subsequently, TMS assessments of motor hot spot location, motor threshold, and recruitment curve were conducted in stroke patients on post-stroke Days 5, 30, and 112. Ongoing standardization was maintained by regular review of patient data and communication between the clinical site and standardization administrator. CONCLUSION: Although TMS methodological approaches vary, a protocol with standardized procedures was successfully developed and implemented. Using this protocol, centers were formally certified to perform TMS-based neurophysiological measures in this clinical trial of stroke patients. The methodology described is potentially valuable to investigators who might construct future multi-site clinical trials using TMS. PMID- 26865991 TI - Evaluation of novel starch-deficient mutants of Chlorella sorokiniana for hyper accumulation of lipids. AB - When green algae are exposed to physiological stresses such as nutrient deprivation, growth is arrested and the cells channel fixed carbon instead into storage compounds, accumulating first starch granules and then lipid bodies containing triacylglycerides. In recent years there has been significant interest in the commercial exploitation of algal lipids as a sustainable source of biodiesel. Since starch and lipid biosynthesis involves the same C3 precursor pool, it has been proposed that mutations blocking starch accumulation should result in increased lipid yields, and indeed several studies have supported this. The fast-growing, thermotolerant alga Chlorella sorokiniana represents an attractive strain for industrial cultivation. We have therefore generated and characterized starch-deficient mutants of C. sorokiniana and determined whether lipid levels are increased in these strains under stress conditions. One mutant (ST68) is shown to lack isoamylase, whilst two others (ST3 and ST12) are defective in starch phosphorylase. However, we find no significant change in the accumulation or profile of fatty acids in these mutants compared to the wild type, suggesting that a failure to accumulate starch per se is not sufficient for the hyper-accumulation of lipid, and that more subtle regulatory steps underlie the partitioning of carbon to the two storage products. PMID- 26865992 TI - Optimization of an in vitro human blood-brain barrier model: Application to blood monocyte transmigration assays. AB - The blood-brain barrier (BBB) is a selectively permeable barrier that separates the circulating blood from the extracellular fluid of the brain and is an essential component in brain homeostasis. In vitro BBB models are valuable supporting tools that can precede and complement animal and human studies of the development and progression of the central nervous system diseases. At present, mono-, co-, and tri-culture models that use porcine, murine, or human cells have been developed. We have optimized a two-dimensional model of the human BBB using primary human brain microvascular endothelial cells and normal human astrocytes. We have validated the effectiveness of our model with transmigration assays of human blood monocytes toward CCL19, a natural ligand of the chemokine receptor CCR7. This model offers the following advantages:*It is simple, convenient, and requires small quantities of material, reagents, and primary cells.*It can be used to monitor cell migration through the BBB.*It can be used to assess brain capillary permeability in the presence of xenobiotic, pro-inflammatory, or other substances. PMID- 26865993 TI - An unusual presentation of filariasis in a nonendemic country. AB - INTRODUCTION: Filariasis is an endemic disease with worldwide distribution in tropical and subtropical regions. It is uncommon in Qatar. The conventional diagnostic procedure is the demonstration of microfilaria in blood smears. Even with its high incidence, it is unusual to detect microfilaria in fine needle aspiration cytology (FNAC) smears. Although the 'filarial dance sign' is rarely documented, it remains a classical ultrasonographic sign in lymphatic filariasis. CASE PRESENTATION: We present a case of a 38-year-old male patient with fever, chills, shortness of breath and a tender warm swelling on his right thigh. Ultrasound of the thigh lesion showed the classical filarial dance sign. Subsequently FNAC from the lesion documented microfilaria in spite of absent peripheral blood eosinophilia and microfilaria. The patient underwent an incision and drainage of the thigh lesion and was treated with ivermectin and diethylcarbamazine. He was subsequently admitted to the medical ward and discharged home after two weeks in a stable condition. CONCLUSION: This case report illustrates the importance of diagnostic tools like ultrasound and FNAC along with a high index of clinical suspicion while evaluating patients presenting with unusual signs and symptoms. We would like to highlight the rarity of filarial presentation in a nonendemic country like Qatar. This case is unique since microfilaria was demonstrated in the pus aspirated from the thigh abscess and showed the filarial dance sign by ultrasound along with involvement of the pleura and pericardium. PMID- 26865994 TI - Varicella-zoster virus associated encephalitis in a patient undergoing haemodialysis. AB - We describe an elderly gentleman with end stage renal disease on haemodialysis who presented with ophthalmic zoster infection and was discharged on oral acyclovir. He presented again a few days later with confusion and expressive dysphasia. Differential diagnosis was mainly between varicella-zoster virus (VZV) associated encephalitis versus acyclovir toxicity. Cerebrospinal fluid analysis confirmed the diagnosis of VZV associated encephalitis and the patient was treated with intravenous acyclovir and steroids with full recovery back to pre admission neurological status. PMID- 26865995 TI - HDAC and HDAC Inhibitor: From Cancer to Cardiovascular Diseases. AB - Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction, and even transcription. HDACs are also post-transcriptional modifiers that regulate the protein acetylation implicated in several pathophysiologic states. HDAC inhibitors have been highlighted as a novel category of anti-cancer drugs. To date, four HDAC inhibitors, Vorinostat, Romidepsin, Panobinostat, and Belinostat, have been approved by the United States Food and Drug Administration. Principally, these HDAC inhibitors are used for hematologic cancers in clinic with less severe side effects. Clinical trials are continuously expanding to address other types of cancer and also nonmalignant diseases. HDAC inhibition also results in beneficial outcomes in various types of neurodegenerative diseases, inflammation disorders, and cardiovascular diseases. In this review, we will briefly discuss 1) the roles of HDACs in the acquisition of a cancer's phenotype and the general outcome of the HDAC inhibitors in cancer, 2) the functional relevance of HDACs in cardiovascular diseases and the possible therapeutic implications of HDAC inhibitors in cardiovascular disease. PMID- 26865996 TI - Signaling Pathways in Osteoclast Differentiation. AB - Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-kappaB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate osteoclast differentiation through regulation of delicate signaling systems. Here, we summarize the critical or essential signaling pathways for osteoclast differentiation including M-CSF-c-Fms signaling, RANKL-RANK signaling, and costimulatory signaling for RANK. PMID- 26865999 TI - Modulation of Melanogenesis by Heme Oxygenase-1 via p53 in Normal Human Melanocytes. AB - As a key regulator of melanogenesis, p53 controls microphthalmia-associated transcription factor (MITF) and tyrosinase expression. The anti-oxidant enzyme heme oxygenase-1 (HO-1) is induced by various forms of cellular stress and diverse oxidative stimuli. However, few studies have examined the role of HO-1 in melanogenesis. Therefore, the aim of this study was to determine the role of HO-1 in melanogenesis and the mechanism underlying this relationship. Cultures of normal human melanocytes were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) or the HO-1 inhibitor zinc protoporphyrin (ZnPP). We then measured the melanin content of the cells. Additional analyses consisted of Western blotting and RT-PCR. The results showed that the cellular melanin content was increased by CoPP and decreased by ZnPP. The Western blot and RT-PCR analyses showed that CoPP increased p53, MITF and tyrosinase levels, and ZnPP reduced all of them. The knockdown of p53 by siRNA transfection was followed by large decreases in the expression levels of p53, MITF and tyrosinase at 3 h of transfection. The presence of CoPP or ZnPP had no significant increased or decreased effects on MITF and tyrosinase levels from 15 h in the siRNA transfectants. Our results suggest that HO-1 modulates melanogenesis in human melanocytes via a p53 dependent pathway. PMID- 26865997 TI - The Neurobiology of Bipolar Disorder: An Integrated Approach. AB - Bipolar disorder is a heterogeneous condition with myriad clinical manifestations and many comorbidities leading to severe disabilities in the biopsychosocial realm. The objective of this review article was to underline recent advances in knowledge regarding the neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutic targets in the treatment of bipolar disorder. To accomplish these goals, an electronic search was undertaken of the PubMed database in August 2015 of literature published during the last 10 years on the pathophysiology of bipolar disorder. A wide-ranging evaluation of the existing work was done with search terms such as "mood disorders and biology," "bipolar disorder and HPA axis," "bipolar disorder and cytokines," "mood disorders and circadian rhythm," "bipolar disorder and oxidative stress," etc. This endeavor showed that bipolar disorder is a diverse condition sharing neurobiological mechanisms with major depressive disorder and psychotic spectrum disorders. There is convincing evidence of crosstalk between different biological systems that act in a deleterious manner causing expression of the disease in genetically predisposed individuals. Inflammatory mediators act in concert with oxidative stress to dysregulate hormonal, metabolic, and circadian homeostasis in precipitating and perpetuating the illness. Stress, whether biologically or psychologically mediated, is responsible for the initiation and progression of the diathesis. Bipolar spectrum disorders have a strong genetic component; severe life stresses acting through various paths cause the illness phenotype. PMID- 26865998 TI - No-Reflow Phoenomenon by Intracoronary Thrombus in Acute Myocardial Infarction. AB - Recently, percutaneous coronary intervention has been the treatment of choice in most acute myocardial infarction cases. Although the results of percutaneous coronary interventions have ben good, the no-reflow phenomenon and distal embolization of intracoronary thrombus are still major problems even after successful interventions. In this article, we will briefly review the deleterious effects of no-reflow and distal embolization of intracoronary thrombus during percutaneous coronary interventions. The current trials focused on the prevention and treatment of the no-reflow phenomenon and intracoronary thrombus. PMID- 26866000 TI - The Effects of Air Pollution on Ischemic Stroke Admission Rate. AB - The present study aimed to determine the relationship between the level of air pollutants and the rate of ischemic stroke (IS) admissions to hospitals. In this retrospective cross-sectional study, stroke admissions (January-March 2012 and 2013) to an emergency department and air pollution and meteorological data were gathered. The relationship between air pollutant levels and hospital admission rates were evaluated using the generalize additive model. In all 379 patients with IS were referred to the hospital (52.5% male; mean age 68.2+/-13.3 years). Both transient (p<0.001) and long-term (p<0.001) rises in CO level increases the risk of IS. Increased weekly (p<0.001) and monthly (p<0.001) average O3 levels amplifies this risk, while a transient increase in NO2 (p<0.001) and SO2 (p<0.001) levels has the same effect. Long-term changes in PM10 (p<0.001) and PM2.5 (p<0.001) also increase the risk of IS. The findings showed that the level of air pollutants directly correlates with the number of stroke admissions to the emergency department. PMID- 26866001 TI - Association of APOE Genotype with Bone Mineral Density in Men and Women: The Dong gu and Namwon Studies. AB - Many studies have investigated relationships between APOE genotype and bone mineral density (BMD). However, the results of these studies have been inconsistent. Few studies have been carried out in Asian populations. We studied the relationship of the APOE gene polymorphism and BMD in two large population based studies. The datasets included the Dong-gu Study (3575 men and 5335 women) and the Namwon Study (2310 men, 3512 women). Lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. APOE genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The APOE genotypes were classified into APOE E2 (E2/E2 and E2/E3), APOE E3 (E3/E3), and APOE E4 (E3/E4 and E4/E4). The genotype distribution of the study population was in Hardy-Weinberg equilibrium. There were no significant differences among APOE genotype groups in lumbar and femoral neck BMD in either cohort. Our data do not support the hypothesis that the APOE genotype is associated with BMD. PMID- 26866002 TI - Clinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single Center Study from 2000 to 2013. AB - We examined the clinical and laboratory characteristics of children newly diagnosed with diabetes mellitus (DM) in a single-center study. We retrospectively reviewed the data of 155 children with DM between January 2000 and December 2013. Of 155 diabetic children, 87 (56.1%) were diagnosed with type 1 DM (T1DM) and 68 (43.9%) with type 2 DM (T2DM). Mean ages at diagnosis were 8.95+/-3.89 years (T1DM) and 13.76+/-2.23 years (T2DM), respectively (p<0.001). There were significant differences in HbA1c, C-peptide, and glutamic acid decarboxylase antibody levels between the T1DM and T2DM groups. Annual numbers of children with DM have increased, and since 2011 the number of children with T2DM has surpassed the number with T1DM. The most common clinical symptom in T1DM was polyuria, and 26.4% of children with T1DM presented initially with diabetic ketoacidosis. In contrast, 60.3% of T2DM children showed glucosuria in a school urine screening, and only 19.1% presented with polydipsia. The rate of positivity for at least more than one islet autoantibody was 77.1% in T1DM and 26.3% in T2DM. Serum C-peptide levels in T2DM were increased up to 12 months after onset and remained >3.59 ng/mL for 36 months. However, serum C-peptide levels in T1DM were slightly increased up to 6 months after onset and gradually decreased to 0.32 ng/mL for 36 months. The prevalence of children with DM has increased over the last 14 years, and the proportion of T2DM patients has rapidly increased since 2009. Because childhood DM is associated with several metabolic and cardiovascular complications, children should be screened for early detection of DM, especially asymptomatic T2DM in children and adolescents. PMID- 26866003 TI - The Diagnostic Value of Pelvic Ultrasound in Girls with Central Precocious Puberty. AB - The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for differentiating central precocious puberty (CPP) from exaggerated thelarche (ET). Because of this test's limitations, previous studies have clarified the clinical and laboratory factors that predict CPP. The present study investigated the early diagnostic significance of pelvic ultrasound in girls with CPP. The GnRH stimulation test and pelvic ultrasound were performed between March 2007 and February 2015 in 192 girls (aged <8 years) with signs of early puberty and advanced bone age. Ninety-three of 192 patients (48.4%) were diagnosed as having CPP and the others (51.6%) as having ET. The CPP group had higher uterine volumes (4.31+/-2.79 mL) than did the ET group (3.05+/-1.97 mL, p=0.03). No significant differences were found in other ultrasonographic parameters. By use of receiver operating characteristic curve analysis, the most predictive parameter for CPP was a uterine volume of least 3.30 mL, with an area under the curve of 0.659 (95% confidence interval: 0.576-0.736). The CPP group had significantly higher uterine volumes than did the ET group, but there were no reliable cutoff values in pelvic ultrasound for differentiating between CPP and ET. Pelvic ultrasound should be combined with clinical and laboratory tests to maximize its diagnostic value for CPP. PMID- 26866004 TI - Vitamin D Levels After Kidney Transplantation and the Risk of Cytomegalovirus Infection. AB - BACKGROUND: Some studies reported an association between low levels of vitamin D and the risk of infections, especially viral infections. Kidney transplant patients are at risk of opportunistic infections; however, no study has been conducted on the association between vitamin D levels and the risk of CMV infection. OBJECTIVES: The aim of this study was to compare the level of vitamin D in two groups of patients with and without CMV infection within four months after the transplantation. Moreover, we aimed to find a relation between vitamin D level, before and after transplantation in each group. PATIENTS AND METHODS: This prospective cohort study was conducted in Baqiyatallah hospital in Tehran in 2013. A total of 82 kidney transplant patients were enrolled and vitamin D levels were measured in them before transplantation. The kidney transplant patients had been followed up for four months and monitored for the presence of cytomegalovirus antigen (CMV Ag) in their blood. In patients with positive CMV Ag, vitamin D level was measured again when they became positive but in other patients it was measured at the end of follow-up; at the end, characteristics of patients and vitamin D levels were compared between the two groups. RESULTS: Of all, 40 patients were CMV Ag positive and 42 patients were negative. In most patients transplanted organs were taken from cadaver (66%) and the most common type of dialysis was hemodialysis (92%). Most participants did not undergo antithymocyte globulin therapy (69%) and pulse corticosteroid therapy (83%). Vitamin D level before transplantation was 17.2 +/- 11.6 ng/mL. In patients with positive results or at the end of follow-up in patients without CMV Ag, vitamin D level was 16.3 +/- 11.4 ng/mL. Only 11% of kidney transplant patients, within four months after transplantation, had a normal level of vitamin D (> 30 ng/mL). There was no significant difference between the two groups for patients' characteristics (P > 0.05). Vitamin D levels, before transplantation and at the time of detecting CMV Ag or at the end of follow-up period in patients without CMV, were not significantly different between the two groups (P > 0.05). However, vitamin D levels decreased in patients with CMV, while it increased in CMV Ag negative patients, which was statistically significant (P = 0.037). CONCLUSIONS: Only 11% of kidney transplant patients, even with a successful transplantation of the kidney and with an acceptable performance of the transplanted kidney, had an adequate level of vitamin D. Although, we did not find any significant association between vitamin D levels and CMV infection during a 4-month follow-up after kidney transplantation. It was observed that, compared with the time before transplantation, vitamin D levels decreased in patients with CMV, while it increased in CMV negative patients. PMID- 26866005 TI - Vaginismus in Iran: A Single Center Report of 7 Years Experience. AB - BACKGROUND: Vaginismus is a sexual disorder that can cause painful intercourse. Although several studies have shown a relationship between higher education and socio-economic level of women with vaginismus, the relationship between demographic characteristics and other variables remains unclear. OBJECTIVES: The present study was conducted to determine the demographic characteristics of women with vaginismus, coming to family health clinic, between 2007 and 2013. PATIENTS AND METHODS: This study is a cross-sectional study that was conducted on 115 clinical records, from early 2007 until the end of 2013, that have received a diagnosis of vaginismus. In these clinical records, the data on female and male age, education and employment, duration of marriage, type of marriage (traditional, virtual, etc.), being a virgin, erectile dysfunction of husband, information of families, sexual satisfaction, marital satisfaction, residential, non-medical types of medical treatment and hymenectomy were derived. RESULTS: The results showed that the average age of women was 29 +/- 5 years and the average age of the spouses was 33 +/- 6 years. Undergraduate education most prominent among women (52%) and spouses (42%). In terms of employment status, most women were housewives (54%) and the majority of male were employees (54%). The most frequent form of marriage was traditional (80%). The maximum elapsed time of marriage was between 1 - 3 years (43%). In most women, the first attempt for intercourse was from the second day of marriage to the end of the first week (73%). Hymenectomy was done by 9% of women. Totally, 45% of the men, the wives of whom were suffering from vaginismus, experienced erectile dysfunction. In 37% of couples, their sexual life was satisfactory. The most referred specialist for treatment was the urologist (17%). In 27% of women with vaginismus, numerous references to a variety of medical specialists and psychologists were also recorded. Of the total, 7% of couples experienced traditional and non-academic treatments. CONCLUSIONS: As vaginismus can affect the stability of marriage, it is necessary to assess sexual dysfunction from all directions, including demographic characteristics and variables that affect the incidence of vaginismus. Therefore, based on the data obtained, we can diagnose and properly treat sexual dysfunction, in time, and teach couples how to deal with it. PMID- 26866007 TI - Effects of Ropivacaine on Postoperative Pain and Peak Expiratory Flow Rate in Patients Undergoing Percutaneous Nephrolithotomy. AB - BACKGROUND: Postoperative analgesic effects of ropivacaine have been demonstrated in various surgical procedures; however, its beneficial effect on postoperative pain relief and ability to breathe out air in urological surgeries, particularly in local interventions such as percutaneous nephrolithotomy (PCNL), has remained uncertain. OBJECTIVES: The aim of this study was to assess the efficacy of ropivacaine on postoperative pain severity and peak expiratory flow (PEF) in patients undergoing PCNL procedure. PATIENTS AND METHODS: This randomized double blinded clinical trial was performed on 55 consecutive adult patients aged 15 to 60 years who underwent Tubeless PCNL surgery. The patients were randomly assigned to instill 30 mL of ropivacaine 0.2% or 30 mL of isotonic saline with the same protocol. The parameters of visual analogue scale (VAS) (for assessment of pain severity) and PEF (for assessment of ability to breathe out air) were measured 4 and 6 hours after completing the procedure. Moreover, the amounts of opioids or analgesics administered within 6 hours after the operation were recorded. RESULTS: We found no difference in the mean pain severity score between the case and control groups 4 hours (P = 0.332) and 6 hours (P = 0.830) after the operation. The mean PEF at baseline was similar in case and control groups (P = 0.738). Moreover, no difference was revealed in PEF index 4 hours (P = 0.398) and 6 hours (P = 0.335) after PCNL between the groups. The mean VAS scores 4 hours after the operation slightly decreased 2 hours later (P < 0.001) in the both groups. Moreover, in the both groups, a sudden decrease in PEF index was observed within 4 hours after the operation and increased with a mild gradient for the next 2 hours. No difference was found in the amount of postoperative analgesic used in the both groups. CONCLUSIONS: Instillation of ropivacaine 0.2% (30 mL) within tubeless PCNL surgery does not have a significant effect on postoperative pain relief and improvement of PEF within 6 hours after the operation. PMID- 26866006 TI - Hemophagocytic Syndrome, an Uncommon Complication of Microscopic Polyangitis: A Case Report From Senegal. AB - INTRODUCTION: We reported a case of hemophagocytic syndrome complicating microscopic polyangitis presented by crescentic glomerulonephritis. CASE PRESENTATION: A 22-year-old female patient originated from Dakar, Senegal presented with nephrotic syndrome and rapidly progressive glomerulonephritis. On physical examination, we noticed hyperchromic diffuse punctilious purpura skin lesions predominant on the trunk, the neck and the upper thigh. Immunology investigations revealed strongly positive anti SSA/Ro and anti-SSB. Anti neutrophil cytoplasmic antibodies had positive results with a peri-nuclear type fluorescence, specific to myeloperoxidase. In optic microscopy, renal biopsy showed a crescentic glomerulonephritis with circumferential cellular and fibrous proliferation affecting 85% of glomeruli. The diagnosis of microscopic polyangitis with renal and skin involvement was retained. The patient received methylprednisolone and cyclophosphamide 700 mg/m(2) every 15 days for the first 3 pulses and every 21 days thereafter. After the 5(th) month, she developed obnubilation, fever and central pancytopenia. Bone marrow aspiration was performed, which showed medullary invasion by macrophages with signs of hemophagocytosis. Diagnosis of hemophagocytic syndrome complicating a microscopic polyangitis was retained and methylprednisolone pulses started. The patient was under hemodialysis after follow-up of about 9 months with stable clinical state. CONCLUSIONS: The occurrence of SAM in pauci-autoimmune vasculitis is rarely described, particularly in Africa. Our case is an illustration of the reality of this association. PMID- 26866008 TI - Ameliorative Effect of Recombinant Human Erythropoietin and Ischemic Preconditioning on Renal Ischemia Reperfusion Injury in Rats. AB - BACKGROUND: Ischemia-reperfusion (IR) injury is one of the most common causes of renal dysfunction. There is increasing evidence about the role of the reactive oxygen species (ROS) in these injuries and endogenous antioxidants seem to have an important role in decreasing the renal tissue injury. OBJECTIVES: The aim of this study was to compare the effect of recombinant human erythropoietin (EPO) and ischemic preconditioning (IPC) on renal IR injury. MATERIALS AND METHODS: Twenty four male Wistar rats were allocated into four experimental groups: sham operated, IR, EPO + IR, and IPC + IR. Rats were underwent 50 minutes bilateral ischemia followed by 24 hours reperfusion. Erythropoietin (5000 IU/kg, i.p) was administered 30 minutes before onset of ischemia. Ischemic preconditioning was performed by three cycles of 3 minutes ischemia followed by 3 minutes reperfusion. Plasma concentrations of urea and creatinine were measured. Kidney samples were taken for reactive oxidative species (ROS) measurement including superoxide dismutase (SOD) activity, glutathione (GSH) contents, and malondialdehyde (MDA) levels. RESULTS: Compared to the sham group, IR led to renal dysfunction as evidenced by significantly higher plasma urea and creatinine. Treatment with EPO or IPC decreased urea, creatinine, and renal MDA levels and increased SOD activity and GSH contents in the kidney. CONCLUSIONS: Pretreatment with EPO and application of IPC significantly ameliorated the renal injury induced by bilateral renal IR. However, both treatments attenuated renal dysfunction and oxidative stress in kidney tissues. There were no significant differences between pretreatment with EPO or application of IPC. PMID- 26866009 TI - Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation. AB - BACKGROUND: Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA) alleles and cytomegalovirus infection (CMV), in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. OBJECTIVES: This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. PATIENTS AND METHODS: This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients' blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. RESULTS: Of all participants, 104 patients (52%) were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient's characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001). Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024); on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020). There was no significant relationship between CMV infection and other HLA alleles. Results of multivariate logistic regression analysis showed that deceased donor renal transplantation (OR = 3.018, 95%CI: 1.662 - 5.480, P < 0.001), presence of HLA-B44 (OR = 4.764, 95%CI: 1.259 - 18.032, P = 0.022) and lack of HLA-B8 (OR = 3.246, 95%CI: 1.030 - 10.230, P = 0.044) were the independent risk factors for developing CMV infection, after kidney transplantation. CONCLUSIONS: The findings of this study showed that deceased donor renal transplantation and the presence of HLA-B44 can make the kidney recipient susceptible to CMV infection after kidney transplantation; on the other hand, the presence of HLA-B8 can have a protective effect. PMID- 26866010 TI - Restless Legs Syndrome: Associated Risk Factors in Hemodialysis Patients. AB - BACKGROUND: Restless legs syndrome (RLS) may be associated with increased morbidity and mortality among end-stage renal disease (ESRD) patients; however, it is a disorder that is neglected in dialysis centers. OBJECTIVES: The goal of this study was to investigate the clinical factors associated with RLS among ESRD patients. PATIENTS AND METHODS: This cross-sectional study was conducted on ESRD patients undergoing maintenance hemodialysis (HD) in three HD centers in Ahvaz city in Southwest Iran. Blood samples were obtained prior to a dialysis session to check the routine laboratory test results and assess the adequacy of dialysis. The presence of RLS was assessed by using the international RLS study group (IRLSSG) diagnostic criteria. The IRLSSG rating scale was also used to evaluate the severity of the RLS symptoms. RESULTS: Of the 139 HD patients enrolled in this study, 60 were female (43.2%) and 79 were male (56.8%), with a mean age of 51.82 +/- 13.31 years. The prevalence of RLS was 15.8% (22 patients), with 50% of them (11 patients) having severe or very severe symptoms. There was a significant relationship between RLS and longer durations of dialysis (P < 0.001). The mean level of serum ferritin was lower in patients without RLS, but it was not significant (P = 0.065). No significant differences were found according to age, gender, dialysis shifts, and hemoglobin (Hb) level among patients with and without RLS. CONCLUSIONS: We conclude that a significant percentage of ESRD patients undergoing maintenance HD have severe or very severe RLS symptoms. The presence of RLS is associated to longer durations of dialysis. PMID- 26866011 TI - Evaluation of Protein-Energy Wasting and Inflammation on Patients Undergoing Continuous Ambulatory Peritoneal Dialysis and its Correlations. AB - BACKGROUND: Protein-energy wasting (PEW) and heightened inflammation are prevalent in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and is a strong risk factor for morbidity and mortality in these patients. Evaluation of PEW, prevalence of inflammation as well as interrelationship between various nutritional indices and inflammation has not been studied in much detail in patients undergoing CAPD. OBJECTIVES: This study was conducted to evaluate the interrelationship between PEW and inflammation in patients undergoing CAPD. PATIENTS AND METHODS: Sixty-three patients undergoing CAPD (M = 28, F = 35) were assessed with regard to their nutritional status and inflammation after a minimum of 3 months CAPD initiation. Nutritional status was assessed by dietary diary, anthropometry, subjective global assessment, and multifrequency bioelectrical impedance analysis (BIA). In addition, their serum albumin, prealbumin, transferrin, and cholesterol level were measured. Also, inflammation in these patients was assessed by High-Sensitivity C-Reactive Protein (hs-CRP > 3 mg/L) and Interleukin-6 (IL-6 > 2 ug/mL). Later on, diagnosis of malnutrition was made based on different methods. Correlation between inflammation and various nutritional assessment indices were analyzed statistically. RESULTS: Mean (SD) age of the patients was 57.6 (11.6) years. The average (SD) calorie and protein intake per day were 25.5 (4.6) kcal and 0.81 (0.2) mg, respectively. The mean and standard deviation of anthropometry variables of body mass index (BMI), mid-arm circumference (MAC), tricipital skin fold thickness (TST), mid-arm muscle circumference (MAMC), and corrected mid-arm muscle area (cMAMA) were 23.7 +/- 5 kg/m(2), 26.3 +/- 4.5 cm, 1.624 +/- 0.4 cm, 25.6 +/- 4.5 cm, and 45.7 +/- 19.7 cm(2), respectively. The mean values of serum protein, albumin, prealbumin, transferrin, cholesterol, triglyceride, hs-CRP, and IL-6 were 5.9 g/dL, 3.0 g/dL, 21.11 mg/dL, 130.6 mg/dL, 155.9 mg/dL, 136.1 mg/dL, 8.8 +/- 7.6 mg/L, and 8.4 +/- 12.2 ug/dL, respectively. Based on subjective global assessment (SGA); 11.63 (17.4%), 34.63 (54%), and 18.65 (28.6%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. According to serum albumin level; 13.63 (21%), 39.63 (62%), and 11.63 (17%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. Finally, based on BMI; 33.63 (52%), 23.63 (37%), and 7.63 (11%) patients undergoing CAPD had normal, moderate, and severe malnutrition status, respectively. About 76.1% and 9.5% of patients undergoing CAPD were malnourished based on lean tissue index (LTI) and fat tissue index (FTI), respectively. Based on hs-CRP and IL-6 findings, 70% (44/63) and 71.8% (45/63) of patients undergoing CAPD had high inflammation, respectively. High sensitive C-reactive protein correlated negatively (significantly) with serum albumin, prealbumin, and transferrin. Interleukin -6 correlated negatively (significantly) with MAC; MAMA; serum albumin, cholesterol, and transferrin. There was significant positive correlation between hs-CRP and IL-6. There is statistically significant difference in total protein intake (g/d), protein intake (g/kg/d), serum protein (g/dL), albumin (g/dL), transferrin (mg/dL), and cholesterol (mg/dL) between patients with and without inflammation. CONCLUSIONS: Protein-energy wasting (80% - 85%) by various methods and inflammation (70%) was very prevalent among patients undergoing CAPD. Inflammatory markers show significant negative correlation with anthropometry and serological markers. Inflammatory markers are suggested to be included in the regular assessment of patients undergoing CAPD, for the better management of protein-energy wasting. PMID- 26866012 TI - Takotsubo Cardiomyopathy With Significant Coronary Stenosis and Atrioventricular Conduction Block: A Rare Case Report With 3 Year Follow-Up. AB - INTRODUCTION: Takotsubo cardiomyopathy (TCMP) is a rare acute cardiomyopathy characterized by acute chest pain syndrome, similar to myocardial infarction, except that no significant stenosis is observed on coronary angiography in patients with this condition; these findings aid the diagnosis of TCMP. CASE PRESENTATION: We discuss an unusual case of TCMP in a 45-year-old woman with complete heart block and significant coronary artery stenosis. Maximal exercise test and perfusion scan after 1 month from the acute event did not show any ischemia; therefore, revascularization was not recommended. Her follow-up with normal echocardiographic data 3 years after the first event showed no recurrence. CONCLUSIONS: The present case and a few previous cases have showed that severe coronary artery disease may be occur in patients with TCMP and that TCMP may be associated with a high-degree atrioventricular block. The association between atrioventricular conduction block and TCMP as well as significant coronary stenosis is rarely reported; therefore, coronary angiography should be performed in all patients with clinical TCMP and the previous definition should be reconsidered. The occurrence of arrhythmia and later recovery is expected in these patients (due to a catecholamine surge). PMID- 26866013 TI - Shortness of Breath and Lower Limb Edema in a 54-Year-Old Woman, Is There Any Cure? AB - INTRODUCTION: Pulmonary hypertension is common among patients with hyperthyroidism, and Graves' disease constitutes the most common cause of thyrotoxicosis. CASE PRESENTATION: We report the case of a female patient admitted to the cardiology department with shortness of breath and pretibial myxedema. The diagnostic work-up revealed combined pre- and post-capillary pulmonary hypertension due to Graves' disease superimposed on left ventricular diastolic dysfunction. Restoration of thyroid function led to normalization of the pulmonary pressure and symptom resolution. CONCLUSIONS: Thyroid disease is a cause of reversible pulmonary hypertension and thus should be appropriately considered in the diagnostic algorithm in patients with dyspnea, clinical signs of hyperthyroidism and elevated pulmonary pressure. PMID- 26866014 TI - Characterization of an Oncolytic Adenovirus Vector Constructed to Target the cMet Receptor. AB - The cMet receptor is a homodimer with tyrosine kinase activity. Upon stimulation with its ligand, hepatocyte growth factor (HGF), the receptor mediates wide physiologic actions. The HGF-cMet signaling pathway is dysregulated in many cancers, which makes cMet an important target for novel therapeutic interventions. Oncolytic adenoviruses (Ads) have been used for the past three decades as a promising therapeutic approach for a wide array of neoplastic diseases. To date, achieving cancer-specific replication of oncolytic Ads has been accomplished by either viral genome deletions or by incorporating tumor selective promoters. To achieve novel specificity of oncolytic Ad infection of cancer cells that overexpress cMet, we inserted the HGF NK2 sequence, corresponding to a competitive antagonist of HGF binding to the cMet receptor, into the Ad serotype 5 (Ad5) fiber gene. The resulting vector, Ad5-pIX-RFP FF/NK2, was rescued, amplified in HEK293 cells, and characterized. Binding specificity and viral infectivity were tested in various cancer cell lines that express varying levels of cMet and hCAR (the Ad5 receptor). We found that Ad5-pIX RFP-FF/NK2 demonstrated binding specificity to the cMet receptor. In addition, there was enhanced viral infectivity and virus replication compared with a non targeted Ad vector. Although NK2 weakly induces cMet receptor activation, our results showed no receptor phosphorylation in the context of an oncolytic Ad virus. In summary, these results suggest that an oncolytic Ad retargeted to the cMet receptor is a promising vector for developing a novel cancer therapeutic agent. PMID- 26866015 TI - Methodological Aspects of the Phase II Study AFF006 Evaluating Amyloid-beta Targeting Vaccine AFFITOPE(r) AD02 in Early Alzheimer's Disease - Prospective Use of Novel Composite Scales. AB - BACKGROUND: Optimized scales and composite outcomes have been proposed as a way to more accurately measure Alzheimer's disease related decline. AFFITOPE(r) AD02, is an amyloid-beta (Abeta)-targeting vaccine to elicit anti-Abeta antibodies. IMM AD04, commonly known as Alum, originally designated as a control agent, appeared to have disease-modifying activity in a multicenter, parallel group phase II study in early AD patients. OBJECTIVES: To develop adapted outcomes for cognition, function and a composite scale with improved sensitivity to decline and treatment effects in early AD (mild plus prodromal AD) based on historical data and to assess these adapted outcomes in this phase II study. DESIGN: Data from public datasets was analyzed using a partial least squares model in order to identify an optimally weighted cognitive outcome, Adapted ADAS-cog, and an optimally weighted ADL outcome, Adapted ADCS-ADL which were prospectively defined as co-primary endpoints for the study and were also combined into a composite scale. Data from 162 patients in the placebo groups of ADCS studies and 156 mild patients in the ADNI I study were pooled for this analysis. The Adapted ADAS-cog scale considered 13 ADAS-cog items as well as several Neuropsychological test items and CogState items, the Adapted ADCS-ADL considered all ADCS-ADL items. After the pre-specified analyses were complete, additional adapted and composite scales were investigated in a post-hoc manner. Evaluation of the adapted and composite scales was performed on Phase II trial data for AFFITOPE(r) AD02 (AFF006, Clinical Trial Identifier: NCT01117818) and historic data in early AD. Least square means, standard deviations, and least squares mean to standard deviation ratios were compared among adapted and composite scales and traditional scales for the 5 treatment groups in the phase II study and overall for the historic data. Treatment effect sizes and p-values were also compared for the phase II study. RESULTS: Cognitive items that were selected for the adapted cognitive scale (aADAS-cog) and had the highest weights were Word Recall, Word Recognition, and Orientation. Delayed Word Recall and Digit Cancellation were among the items excluded due to lack of improved sensitivity to decline. Highly weighted ADL items included in the adapted functional scale (aADCS-ADL) were using the telephone, traveling, preparing a meal/snack, selecting clothing, shopping and using appliances. Excluded items were primarily basic ADLs such as eating, walking, toileting and bathing. Comparisons between traditional scales and primary outcome adapted scales show improved sensitivity to group differences with the adapted scales in the phase II trial. Most of the improvement in the sensitivity of the aADAS-cog and the aADCS-ADL is due to a larger treatment difference observed rather than the improved sensitivity to decline in the comparison groups. CONCLUSION: To our knowledge, this is the first study to prospectively use optimized scales as primary endpoints and to demonstrate the superior power of optimized scales and composites in early disease. Although it is possible that the treatment difference between randomized groups is due to a factor other than the treatment itself, for instance baseline imbalance, the improved power to detect these differences still argues in favor of the adapted scales. The issue of oversensitivity to detect treatment effects is controlled by selection of the alpha level for significance, and in our case will happen less than 5% of the time. Clinical relevance of the treatment difference should be assessed separately from statistical significance, and in this phase II study, is supported by significant or similar sizes of effect on function, behaviour and quality of life outcomes, which are important to patients and caregivers. PMID- 26866016 TI - The Clinical and Experimental Vaccine Research has been selected for coverage in Emerging Sources Citation Index of Web of Science. PMID- 26866017 TI - The prevention of pneumococcal infections. PMID- 26866018 TI - Recent update in HIV vaccine development. AB - Despite the tremendous efforts to develop a successful human immunodeficiency virus (HIV) vaccine, the quest for a safe and effective HIV vaccine seems to be remarkably long and winding. Disappointing results from previous clinical trials of VaxGen's AIDSVAXgp120 vaccine and MRKAd5 HIV-1 Gag/Pol/Nef vaccine emphasize that understanding the correlates of immune protection in HIV infection is the key to solve the puzzle. The modest vaccine efficacy from RV144 trial and the successive results obtained from the correlate of risk analysis have reinvigorated the HIV vaccine research field leading to various novel strategies. This paper will review the brief history and recent advances in HIV vaccine development. PMID- 26866019 TI - Recent vaccine technology in industrial animals. AB - Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with the PED virus spike gene. Recombinant vaccines can be produced by substitution of the target gene in the VEE vector. Both of these new vaccine technologies made it possible to control the infectious disease efficiently in a relatively short time. PMID- 26866020 TI - Cloning, expression and purification flagellar sheath adhesion of Helicobacter pylori in Escherichia coli host as a vaccination target. AB - PURPOSE: Helicobacter pylori is a widely distributed gram-negative bacterium that infects the human stomach and duodenum. HpaA is a H. pylori-specific lipoprotein that has been shown to be an effective protective antigen against H. pylori infection. HpaA of H. pylori as a vaccine antigen is fully competent for stimulation of immune responses. The aim of this project is cloning, expression, and purification flagellar sheath adhesion of H. pylori in Escherichia coli host by fast protein liquid chromatography (FPLC) as a vaccination target. MATERIALS AND METHODS: The hpaA gene was inserted into pET28a (+) as cloning and expression vectors respectively. The recombinant plasmid (pET-hpaA) was subjected to sequencing other than polymerase chain reaction (PCR) and digestion analysis. Protein expression was induced by adding 1 mM isopropyl-beta-D-thiogalactoside to cultures of E. coli strain BL21 transformed with pET-hpaA. Protein expression assessed with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) analysis. Protein purification of flagellar sheath adhesion was by FPLC. RESULTS: The restriction endonuclease digestion, PCR amplification analysis showed that the hpaA gene of 730 bp was amplified from H. pylori DNA and sequencing analysis of the pET-hpaA confirmed the cloning accuracy and in frame insertion of hpaA fragment. SDS-PAGE analysis showed the expression of an approximately 29,000 Da protein. CONCLUSION: Sequencing results along with SDS PAGE analysis confirms the expression of recombinant hpaA in the heterologous E. coli BL21. Conclusion A prokaryotic expression system for hpaA gene was successfully constructed. These results indicate that production of a specific recombinant protein is an alternative and potentially more expeditious strategy for development of H. pylori vaccine. PMID- 26866021 TI - Comparison of the antigenic relationship between Japanese encephalitis virus genotypes 1 and 3. AB - PURPOSE: The Japanese encephalitis virus (JEV) genotype circulating in Korea has changed from G3 to G1. Therefore, the purpose of this study was to compare the antigenic relationship between the two genotypes by using antibody tests. MATERIALS AND METHODS: Blood samples from 42 sows and 216 horses were collected, and their seroprevalence was monitored using the hemagglutination inhibition and virus neutralization tests. Antisera against JEV G1 and G3 were isolated and prepared from guinea pigs. The cross-reactivity of these two viruses was then compared using the neutralizing antibody test. RESULTS: We found that there was a difference in the seropositive ratios of JEV G1 and G3. However, the difference was dependent on the antibody test used. There was also an observed difference in the antigenicity between the two genotypes, as ascertained using the neutralizing antibody test. CONCLUSION: There is an evident difference in JEV antigenicity between the genotypes G1 and G3. Therefore, we propose monitoring of the seroprevalence of JEV, and reevaluating the antigenicity of the current vaccine by using the relevant tests. PMID- 26866022 TI - Assessment of immunological markers and booster effects of Ag85B peptides, Ag85B, and BCG in blood of BCG vaccinated children: a preliminary report. AB - PURPOSE: In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette-Guerin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. MATERIALS AND METHODS: Fifty children from 1 month to 18 years of age were randomized for the study. Blood samples were collected from 27 participants with/without BCG vaccination. Immunological markers (anti-BCG, interferon gamma [IFN-gamma], and adenosine deaminase activity) were assessed in both serum and PBMCs of children. Children with low levels of protective immunological markers were further recruited and their PBMCs were boosted with BCG, Ag85B, and Ag85B peptides. RESULTS: Children in age group of 4-6 years were associated with significantly (p<0.05) higher BCG-specific IgG and IFN-gamma levels compared to those in age group greater than 10 years. Vaccinated children had greater repertoire of immunological memory which on in vitro stimulation with BCG showed increase in BCG-specific response compared to unvaccinated controls. Assessment of booster effects of BCG, Ag85B, and Ag85B peptides in PBMCs of children revealed greater potential of peptides to boost BCG induced immunity compared to BCG and Ag85B. CONCLUSION: To conclude, children within age 4-6 years are associated with high immunological markers which eventually diminish with age thereby suggesting need for booster dose in later years. Mycobacterium tuberculosis peptides along with BCG may be used as attractive candidates to boost such waning BCG induced immunity in children. PMID- 26866023 TI - In silico analysis of an envelope domain III-based multivalent fusion protein as a potential dengue vaccine candidate. AB - PURPOSE: Dengue virus infection is now a global problem. Currently, there is no licensed vaccine or proven antiviral treatment against this virus. All four serotypes (1-4) of dengue virus can infect human. An effective dengue vaccine should be tetravalent to induce protective immune responses against all four serotypes. Most of dengue vaccine candidates are monovalent, or in the form of physically mixed multivalent formulations. Recently envelope protein domain III of virus is considered as a vaccine candidate, which plays critical roles in the most important viral activities. Development of a tetravalent protein subunit vaccine is very important for equal induction of immune system and prevention of unbalanced immunity. Here, we have presented and used a rational approach to design a tetravalent dengue vaccine candidate. MATERIALS AND METHODS: We designed a multi domain antigen by fusing four consensus domain III sequences together with appropriate hydrophobic linkers and used several types of bioinformatics software and neural networks to predict structural and immunological properties of the designed tetravalent antigen. RESULTS: We designed a tetravalent protein (EDIIIF) based on domain III of dengue virus envelope protein. According to the results of the bioinformatics analysis, the constructed models for EDIIIF protein were structurally stable and potentially immunogenic. CONCLUSION: The designed tetravalent protein can be considered as a potential dengue vaccine candidate. The presented approach can be used for rational design and in silico evaluation of chimeric dengue vaccine candidates. PMID- 26866024 TI - A potent multivalent vaccine for modulation of immune system in atherosclerosis: an in silico approach. AB - PURPOSE: Atherosclerosis is classically defined as an immune-mediated disease characterized by accumulation of low-density lipoprotein cholesterol over intima in medium sized and large arteries. Recent studies have demonstrated that both innate and adaptive immune responses are involved in atherosclerosis. In addition, experimental and human models have recognized many autoantigens in pathophysiology of this disease. Oxidized low-density lipoproteins, beta2 glycoprotein I (beta-2-GPI), and heat shock protein 60 (HSP60) are the best studied of them which can represent promising approach to design worthwhile vaccines for modulation of atherosclerosis. MATERIALS AND METHODS: In silico approaches are the best tools for design and evaluation of the vaccines before initiating the experimental study. In this study, we identified immunogenic epitopes of HSP60, ApoB-100, and beta-2-GPI as major antigens to construct a chimeric protein through bioinformatics tools. Additionally, we have evaluated physico-chemical properties, structures, stability, MHC binding properties, humoral and cellular immune responses, and allergenicity of this chimeric protein by means of bioinformatics tools and servers. RESULTS: Validation results indicated that 89.1% residues locate in favorite or additional allowed region of Ramachandran plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, the epitopes in the chimeric protein had strong potential to induce both the B-cell and T-cell mediated immune responses. CONCLUSION: Our results supported that this chimeric vaccine could be effectively utilized as a multivalent vaccine for prevention and modulation of atherosclerosis. PMID- 26866025 TI - Immunogenicity and efficacy of Rabivac vaccine for animal rabies control in Morocco. AB - PURPOSE: To fight animal rabies, Moroccan veterinary authorities organize annual dog mass vaccination campaigns using Rabivac vaccine, an inactivated adjuvanted cell culture veterinary rabies vaccine. Two experiments were undertaken to assess the efficacy and immunogenicity of Rabivac. MATERIALS AND METHODS: The first experiment involved 13 caged dogs (8 vaccinated and 5 negative controls). Dogs were bled at day 0 (D0) and at days D7, D14, D21, D28, D35, D49, D56, D64, D70, D77, D84, D91, D98, D105, D112, and D119 post-vaccination. At D121, a virulent challenge was performed. After 70 days monitoring period, seven out of eight vaccinated dogs survived the challenge (one dog succumbed to a mesenteric torsion accident) and four out of five controls succumbed. All vaccinated dogs seroconverted and the control dogs remained negative. The second experiment consisted in a field study involving 919 owned dogs randomly selected in eight Moroccan districts located in different parts of the country. The dogs were identified and vaccinated by the parenteral route and bled on the vaccination day (D0) and on D30. RESULTS: Ninety-two percent of dogs developed a positive rabies virus neutralizing antibody response to vaccination and 24% were positive at D0, suggesting that dogs were previously vaccinated. The increase in rabies antibody titers was highly significant in all districts. No significant difference seemed occurring between the geographical status (rural, semiurban, or urban) of the districts on the results obtained. CONCLUSION: Rabivac is efficacious both in experimental and field conditions. This supports its use in dog mass vaccination campaigns. PMID- 26866026 TI - Augmented immune responses in pigs immunized with an inactivated porcine reproductive and respiratory syndrome virus containing the deglycosylated glycoprotein 5 under field conditions. AB - PURPOSE: Porcine reproductive and respiratory syndrome virus (PRRSV) leads to major economic losses in the swine industry. Vaccination is the most effective method to control the disease by PRRSV. MATERIALS AND METHODS: In this study, the efficacy of a glycoprotein (GP) 5-modified inactivated vaccine was investigated in pigs. The study was performed in three farms: farm A, which was porcine reproductive and respiratory syndrome (PRRS)-negative, farm B (PRRS-active), which showed clinical signs of PRRS but had not used vaccines, and farm C (PRRS stable), which had a history of endemic PRRS over the past years, but showed no more clinical signs after periodic administration of modified live virus vaccine. RESULTS: The inactivated vaccine induced great enhancement in serum neutralizing antibody titer, which was sufficient to protect pigs from further infections of PRRSV in a farm where pre-existing virus was circulating. CONCLUSION: These results indicated that vaccination with the inactivated vaccine composed of viruses possessing deglycosylated GP5 would provide enhanced protection to pigs from farms suffering from endemic PRRSV. PMID- 26866027 TI - In silico analysis of Brucella abortus Omp2b and in vitro expression of SOmp2b. AB - PURPOSE: At present, there is no vaccine available for the prevention of human brucellosis. Brucella outer membrane protein 2b (Omp2b) is a 36 kD porin existed in common Brucella pathogens and it is considered as priority antigen for designing a new subunit vaccine. MATERIALS AND METHODS: In the current study, we aimed to predict and analyze the secondary and tertiary structures of the Brucella abortus Omp2b protein, and to predict T-cell and B-cell epitopes with the help of bioinformatics tools. Subsequently, cloning and expression of the short form of Omp2b (SOmp2b) was performed using pET28a expression vector and Escherichia coli BL21 host, respectively. The recombinant SOmp2b (rSOmp2b) was purified with Ni-NTA column. RESULTS: The recombinant protein was successfully expressed in E. coli host and purified under denaturation conditions. The yield of the purified rSOmp2b was estimated by Bradford method and found to be 220 ug/mL of the culture. CONCLUSION: Our results indicate that Omp2b protein has a potential to induce both B-cell- and T-cell-mediated immune responses and it can be evaluated as a new subunit vaccine candidate against brucellosis. PMID- 26866028 TI - Novel foot-and-mouth disease virus in Korea, July-August 2014. AB - Despite nation-wide immunization with O, A, and Asia 1 type vaccines in Republic of Korea, foot-and-mouth disease type O occurred again in July 2014 after three years and three months. This virus was a Mya-98 strain of the Southeast Asian topotype and was most similar to the identified type that circulated in East Asia in 2014. This was new virus with the deletion of 23 amino acids in 3A/3B1 region and low pathogenic property. PMID- 26866029 TI - Clinical characteristics and outcome of cancer diagnosed during pregnancy. AB - OBJECTIVE: The aim of this study is to describe the clinical characteristics and outcome of cancer diagnosed during pregnancy. METHODS: This is a retrospective cohort study of women who were diagnosed with cancer during pregnancy at a tertiary academic hospital between 1995 and 2013. Maternal characteristics, gestational age at diagnosis, and type, stage, symptoms and signs of cancer for each patient were retrieved from the medical records. The cancer treatment, pregnancy management and the subsequent perinatal and maternal outcomes for each cancer were assessed. RESULTS: A total of 87 women were diagnosed with cancer during pregnancy (172.6 cases per 100,000 deliveries). The most common cancer was breast cancer (n=20), followed by gastrointestinal (n=17), hematologic (n=13), thyroid (n=11), central nervous system (n=7), cervical (n=7), ovarian (n=5), lung (n=3), and other cancers (n=4). Eighteen (20.7%) patients terminated their pregnancies. In the 69 (79.3%) patients who maintained their pregnancies, one patient miscarried and 34 patients delivered preterm. Of the preterm babies, 24 (70.6%) were admitted to the neonatal intensive care unit and 3 (8.8%) of those expired. The maternal mortality rate was 31.0%, with highest rate seen with lung cancers (66.7%), followed by gastrointestinal (50.0%), central nervous system (50.0%), hematologic (30.8%), breast (25.0%), ovarian (20.0%) cervical (14.3%), and thyroid cancers (0%). CONCLUSION: The clinical characteristics and outcome of cancer during pregnancy were highly variable depending on the type of cancer. However, timely diagnosis and appropriate management of cancer during pregnancy may improve both maternal and neonatal outcome. PMID- 26866030 TI - Gestational age at delivery and neonatal outcome in uncomplicated twin pregnancies: what is the optimal gestational age for delivery according to chorionicity? AB - OBJECTIVE: To investigate the neonatal outcome according to the gestational age at delivery and to determine the optimal timing for delivery in uncomplicated monochorionic and dichorionic twin pregnancies. METHODS: This is a retrospective cohort study of women with uncomplicated twin pregnancies delivered at or beyond 35 weeks of gestation from 1995 to 2013. The primary outcome was neonatal composite morbidity, which was defined as when either one or both twins have one or more of the followings: fetal death after 35 weeks gestation, admission to neonatal intensive care unit, mechanical ventilator requirement, respiratory distress syndrome and neonatal death. To determine the optimal gestational age for delivery according to chorionicity, we compared the neonatal composite morbidity rate between women who delivered and women who remained undelivered at each gestational week in both monochorionic and dichorionic twin pregnancies. RESULTS: A total of 697 twin pregnancies were included (171 monochorionic and 526 dichorionic twins). The neonatal composite morbidity rate significantly decreased with advancing gestational age at delivery and its nadir was observed at 38 and >=39 weeks of gestation in monochorionic and dichorionic twins, respectively. However, the composite morbidity rate did not differ between women who delivered and women who remained undelivered >=36 and >=37 weeks in monochorionic and dichorionic twins, respectively. CONCLUSION: Our data suggest that the optimal gestational age for delivery was at >=36 and >=37 weeks in uncomplicated monochorionic and dichorionic twin pregnancies, respectively. PMID- 26866031 TI - Post-cerclage ultrasonographic cervical length can predict preterm delivery in elective cervical cerclage patients. AB - OBJECTIVE: To evaluate the usefulness of transvaginal ultrasound measurements of cervical length before and after elective prophylactic cervical cerclage in predicting preterm delivery before 32 weeks of gestation. METHODS: Women who underwent an elective cerclage operation at 14 to 19 weeks of gestation and who delivered between January 2004 and December 2009 were enrolled in this study (n=52). Ultrasonography was performed to measure cervical length before and after cerclage. The primary outcome was defined as preterm delivery before 32 weeks of gestation. A receiver operating characteristic curve was used to determine the most discriminating cut-off values of ultrasonographic cervical parameters predictive of preterm delivery before 32 weeks of gestation. RESULTS: Among the 52 patients studied, ten delivered before 32 weeks of gestation. Among the ultrasonographic cervical parameters compared, only the cervical length after cerclage was significantly different (shorter) in patients who delivered before 32 weeks of gestation (P=0.037) compared to that of those who delivered after 32 weeks of gestation in univariate and multivariate analyses (odds ratio, 0.402; 95% confidence interval, 0.174 to 0.925; P=0.021). The receiver operating characteristic curve showed that a cervical length of 25 mm or less after cerclage was predictive of preterm delivery before 32 weeks of gestation (area under curve, 0.71; 95% confidence interval, 0.56 to 0.87; P=0.029) with a sensitivity of 91.0% and a specificity of 30.0%. CONCLUSION: Patients with a cervical length less than 25 mm after elective cerclage may be at higher risk of preterm delivery before 32 weeks of gestation. PMID- 26866032 TI - Fertility-preserving treatment in complex atypical hyperplasia and early endometrial cancer in young women with oral progestin: Is it effective? AB - OBJECTIVE: The aim of this study is to assess the effectiveness of oral progestin treatment in women diagnosed with complex atypical hyperplasia (CAH) or grade 1 endometrial cancer (G1EC), who desire to preserve their fertility, as alternative treatment to a hysterectomy. METHODS: We reviewed the medical records of women younger than 45 years old that had been diagnosed with CAH or G1EC, who expressed a desire to preserve their fertility using alternative treatment at our institution. Women without evidence of myometrial invasion on pelvic magnetic resonance imaging scans were included. The study period was between 2004 and 2014. Endometrial biopsies were taken at follow-up appointments. RESULTS: We identified 31 young women with CAH or G1EC. The median age was 33 years old (range, 20 to 41), and the median period of time undertaking the treatment was 5 months (range, 1 to 12). Twenty-three patients (74.2%) achieved complete remission (CR; median time to CR was 3 months; range, 1 to 22), 16 patients (88.9%) with CAH and 7 (53.8%) with G1EC achieved CR. 6 patients (26.1%) who had achieved CR, had recurrence of the disease (median time from CR to recurrence was 12.5 months; range, 4 to 18). Eight patients (25.8%) finally underwent a hysterectomy. CONCLUSION: Oral progestin therapy is an alternative treatment for women with CAH or G1EC who desire fertility preservation. However, more prospective studies are needed for standard progestin regimen. Also, there still remains a risk of disease progression and recurrence. Therefore, close follow-up is important during treatment and after CR. In addition, a hysterectomy is recommended as a definitive treatment after completion of childbearing. PMID- 26866033 TI - Effects of different add-back regimens on hypoestrogenic problems by postoperative gonadotropin-releasing hormone agonist treatment in endometriosis. AB - OBJECTIVE: To compare the efficacy of different add-back regimens on hypoestrogenic symptoms during postoperative gonadotropin-releasing hormone (GnRH) agonist treatment in endometriosis patients. METHODS: This prospective cohort study included reproductive-aged women who underwent conservative laparoscopic surgery for ovarian endometriosis and received add-back therapy during a 6-month course of GnRH agonist therapy after surgery. Participants received one of four different add-back regimens: 1 mg of estradiol valerate, 2.5 mg of tibolone, or a combination of 1 mg of estradiol and 2 mg of drospirenone or 0.5 mg of norethisterone acetate. Changes in quality of life, hypoestrogenic symptoms, and bone mineral density were compared according to add-back regimens. RESULTS: A total of 57 participants completed a 6-month course of GnRH agonist and add-back therapy. All components of quality of life did not differ across groups. However, within the same treatment group, social relationship factors decreased significantly with estradiol valerate and tibolone alone, and environmental factors decreased significantly with estradiol valerate alone. Menopausal Rating Scale score did not change significantly, but the incidence of hot flushes significantly decreased with a combination of estradiol and norethisterone acetate. Bone mineral densities at the lumbar spine declined significantly after treatment in all groups except with a combination of estradiol and norethisterone acetate. CONCLUSION: This preliminary study suggests that an add-back regimen containing estradiol valerate and norethisterone acetate may have better efficacy in terms of quality of life, hypoestrogenism-associated symptoms, and bone mineral density. PMID- 26866034 TI - Total laparoscopic hysterectomy via suture and ligation technique. AB - OBJECTIVE: The term 'total laparoscopic hysterectomy (TLH) with classical suture method' refers to a surgical procedure performed using only sutures and ligations with intracorporeal or extracorporeal ties, without using any laser or electronic cauterization devices during laparoscopic surgery as in total abdominal hysterectomy. However, the method is not as widely used as electric coagulation equipment for TLH because further advances in technology and surgical technique are required and operative time can take longer. In the current study, we evaluated the benefits of the classical suture method for TLH. METHODS: This study retrospectively reviewed patients who received TLH using the classical suture method from August 2005 to April 2014. The patients' baseline characteristics were analyzed, including age, parity, cause of operation, medical and surgical history. Surgical outcomes analyzed included the weight of the uterus, operative time, complications, changes in hemoglobin level, blood transfusion requirements, and postoperative hospital stay. RESULTS: Of 746 patients who underwent TLH with the classical suture method, mean operation time was 96.9 minutes. Mean average decline in hemoglobin was 1.6 g/dL and transfusion rate was 6.2%. Urinary tract injuries were reported in 8 patients. Urinary tract injuries comprised 6 cases of bladder injury and 3 cases of ureter injury. There were no cases of vaginal stump infection, hematoma, bowel injury or abdominal wound complication. All cases involving complications occurred before 2010. CONCLUSION: The classical suture method for TLH presents tolerable levels of complications and blood loss. Advanced surgical skill is expected to decrease operation time and complications. PMID- 26866035 TI - Vasomotor symptoms and the homeostatic model assessment of insulin-resistance in Korean postmenopausal women. AB - The aim of this cross-sectional study was to evaluate the association between vasomotor symptoms (VMS) and insulin resistance, which can be postulated by the homeostatic model assessment (HOMA) index. This study involved 1,547 Korean postmenopausal women (age, 45 to 65 years) attending a routine health check-up at a single institution in Korea from January 2010 to December 2012. A menopause rating scale questionnaire was used to assess the severity of VMS. The mean age of participants was 55.22+/-4.8 years and 885 (57.2%) reported VMS in some degree. The mean HOMA index was 1.79+/-0.96, and the HOMA index increased with an increase in severity of VMS (none, mild, moderate and severe) in logistic regression analysis (beta=0.068, t=2.665, P =0.008). Insulin resistance needs to be considered to understand the linkage between VMS and cardiometabolic disorders. PMID- 26866036 TI - Successful pregnancy and delivery of a patient with congenital adrenal hyperplasia. AB - Congenital adrenal hyperplasia (CAH) during pregnancy is a rare condition. Only a few cases have been reported in the literature. CAH patients has lower pregnancy rate compared to normal women. A 27-year-old nulliparous woman, a diagnosed case of 21-hydroxylase deficient simple virilising form of classic CAH visited. She got pregnant spontaneously without any trial of assisted reproductive technology. At the age of 12, she underwent clitoral resection and vaginoplasty. She took dexamethasone or prednisolone after operation. She delivered healthy singleton female baby by cesarean section. Four years later, she delivered healthy singleton female baby by repeat cesarean section. Two female babies have shown normal external genitalia. Here, we report a case of successful pregnancy and delivery in a patient with CAH. PMID- 26866037 TI - Fetal goiter conservatively monitored during the prenatal period associated with maternal and neonatal euthyroid status. AB - Congenital goiter is considered a rare occurrence, and may be related to hypothyroidism, hyperthyroidism, or euthyroidism. In this report, we describe a case of fetal goiter identified in the 34th gestational week in a 41-year-old secundigravida with normal thyroid functions. A conservative approach was followed; the fetal goiter was monitored via ultrasound, which suggested this was a case of hyperthyroidism. After the birth, tests indicated that the newborn was euthyroidic. Consequently, a more detailed study using non-invasive procedures was deemed necessary to discover the precise cause of the fetal goiter during the gestational period. PMID- 26866038 TI - Impaction of an intrathoracic kidney acted as a shield against herniation of the abdominal viscera in a case of right congenital diaphragmatic hernia. AB - We describe a case of an intrathoracic kidney combined with right congenital diaphragmatic hernia (CDH) that was diagnosed at 32 weeks of gestation. Although it has been well established that a right CDH shows a poorer outcome than a left CDH, our present case showed a good outcome because there was no herniation of other abdominal viscera, except for the right kidney. Our findings in this case indicate that impaction of the intrathoracic kidney may act as a 'shield' against further herniation of other abdominal viscera into the thoracic cavity. PMID- 26866039 TI - Successful vaginal birth after prior cesarean section in a patient with pyoderma gangrenosum. AB - Pyoderma gangrenosum is an extremely rare chronic cutaneous disease causing severe ulceration. It can be developed after minor trauma or surgical procedure. The typical features mimic acute infection site, however the treatment methods are opposing since pyoderma gangrenosum is improved with the use of corticosteroids, not antibiotic therapy. We here report a patient who had been diagnosed for acute infection after cesarean delivery in 2011 and treated with a number of antibiotics, but failed to recover. The patient had suffered from pain of the disease and also renal failure caused by antibiotics. Ultimately she had been diagnosed as pyoderma gangrenosum and managed successfully with steroids. For her next pregnancy in 2013, we tried vaginal delivery after prior cesarean section and it was uneventful during and after delivery. PMID- 26866040 TI - Intra-amniotic thyroxine to treat fetal goiter. AB - A 35-year-old pregnant woman visited our department and had been treated with 100 ug of daily oral levothyroxine for hypothyroidism. An ultrasonography screening was performed at 25 weeks gestation and revealed a fetal goiter and an increased amniotic fluid volume. Fetal hypothyroidism was confirmed by cordocentesis and amniotic hormone levels at 26 weeks gestation. We treated the mother with 200 ug of daily oral levothyroxine to optimize the transplacental transfer. A total of four intra-amniotic injections of levothyroxine were administered, resulting in progressive reduction in the fetal thyroid volume of goiter as measured by 3D ultrasonography and increased amniotic fluid volume. Following birth, neonatal serum thyroid stimulating hormone level was within the normal range, but free T4 was reduced. Based on this case, we suggest that monitoring amniotic fluid thyroid hormone concentration and intra-amniotic levothyroxine injection can be used to reduce the thyroid volume of goiters and to prevent polyhydramnios. PMID- 26866041 TI - Total vaginectomy for refractory vaginal intraepithelial neoplasia III of the vaginal vault. AB - Vaginal intraepithelial neoplasia III, is a relatively rare disease. Consequently standard treatments for this disease were not established until recently. Although several convenient methods, such as laser ablation, 5-fluorouracil topical injection, and radiation therapy, have been applied for treating these lesions, surgical treatments, including vaginectomy, have not yet been attempted, as they would likely be accompanied by technical difficulties and various complications. Herein, we report a case of refractory vaginal intraepithelial neoplasia III in the vaginal vault that was successfully treated with a total vaginectomy. PMID- 26866042 TI - Torsion of a parasitic myoma that developed after abdominal myomectomy. AB - Iatrogenic parasitic myomas are rare. The condition is defined by the presence of multiple smooth-muscle tumorous nodules in the peritoneal cavity. This may be attributable to seeding of myoma particles during uterine surgery. The clinical course is usually indolent. The disease is often asymptomatic and is usually discovered only incidentally. A 38-year-old woman who had undergone abdominal myomectomy 7 months prior presented with acute abdominal pain and a huge pelvic mass. We performed exploratory laparotomy. A parasitic mass 17 cm in diameter with a twisted omental pedicle was identified. En bloc excision of the mass and omentum was performed, followed by total abdominal hysterectomy. Histopathological examination of multiple sections revealed features compatible with an infarcted leiomyoma. Thus, we present a very rare case of an iatrogenic, rapidly growing parasitic myoma complicated by omental torsion (which caused the acute abdominal pain). We also offer a literature review. PMID- 26866045 TI - Pilot Study and Review: Physiological Differences in BDNF, a Potential Biomarker in Males and Females with Autistic Disorder. AB - AIMS: There is a need for more biologic research in autistic disorder (AD) to determine if biomarkers exist that would be useful for correlating to symptom severity and/or clinical improvement during treatment. Given the fact that AD is 4 times more common in males than females, gender differences in physiological biomarkers may be present. One potential biomarker that has begun to be studied is brain-derived neurotropic factor (BDNF), a peptide involved in the regulation of neuronal cell survival, differentiation, and plasticity, and possessing an ability to influence neurotransmitter systems by modulating gene expression. This pilot study examined whether serum BDNF differed according to gender in children with AD and whether differences were associated with a behavioral phenotype or severity of illness. STUDY DESIGN: Data for this investigation were collected during the participants' baseline visit of an intervention study. Participants were males (n=29) and females (n=7), aged 5 to 12 years diagnosed with AD. Baseline serum BDNF concentration was determined for comparison to clinical ratings using an autism severity measure and the Pervasive Developmental Disorder Behavior Inventory (PDD-BI). RESULTS: BDNF serum concentrations were higher in females (p<0.049). The baseline BDNF value corresponded significantly to hyperactivity in females (p<0.0002) but not in males. BDNF did not correlate with severity of disease in either gender. CONCLUSION: Although this is a small study, a better understanding of the central role of BDNF may provide insight into the pathophysiology of the disease and elucidate why gender differences exist in prevalence and behavioral phenotype of AD. PMID- 26866046 TI - Urban microbial ecology of a freshwater estuary of Lake Michigan. AB - Freshwater estuaries throughout the Great Lakes region receive stormwater runoff and riverine inputs from heavily urbanized population centers. While human and animal feces contained in this runoff are often the focus of source tracking investigations, non-fecal bacterial loads from soil, aerosols, urban infrastructure, and other sources are also transported to estuaries and lakes. We quantified and characterized this non-fecal urban microbial component using bacterial 16S rRNA gene sequences from sewage, stormwater, rivers, harbor/estuary, and the lake surrounding Milwaukee, WI, USA. Bacterial communities from each of these environments had a distinctive composition, but some community members were shared among environments. We used a statistical biomarker discovery tool to identify the components of the microbial community that were most strongly associated with stormwater and sewage to describe an "urban microbial signature," and measured the presence and relative abundance of these organisms in the rivers, estuary, and lake. This urban signature increased in magnitude in the estuary and harbor with increasing rainfall levels, and was more apparent in lake samples with closest proximity to the Milwaukee estuary. The dominant bacterial taxa in the urban signature were Acinetobacter, Aeromonas, and Pseudomonas, which are organisms associated with pipe infrastructure and soil and not typically found in pelagic freshwater environments. These taxa were highly abundant in stormwater and sewage, but sewage also contained a high abundance of Arcobacter and Trichococcus that appeared in lower abundance in stormwater outfalls and in trace amounts in aquatic environments. Urban signature organisms comprised 1.7% of estuary and harbor communities under baseflow conditions, 3.5% after rain, and >10% after a combined sewer overflow. With predicted increases in urbanization across the Great Lakes, further alteration of freshwater communities is likely to occur with potential long term impacts on the function of estuarine and nearshore ecosystems. PMID- 26866047 TI - Separation of the global and local components in functional near-infrared spectroscopy signals using principal component spatial filtering. AB - Global systemic effects not specific to a task can be prominent in functional near-infrared spectroscopy (fNIRS) signals and the separation of task-specific fNIRS signals and global nonspecific effects is challenging due to waveform correlations. We describe a principal component spatial filter algorithm for separation of the global and local effects. The effectiveness of the approach is demonstrated using fNIRS signals acquired during a right finger-thumb tapping task where the response patterns are well established. Both the temporal waveforms and the spatial pattern consistencies between oxyhemoglobin and deoxyhemoglobin signals are significantly improved, consistent with the basic physiological basis of fNIRS signals and the expected pattern of activity associated with the task. PMID- 26866048 TI - Full receiver operating characteristic curve estimation using two alternative forced choice studies. AB - Task-based medical image quality is typically measured by the degree to which a human observer can perform a diagnostic task in a psychophysical human observer study. During a typical study, an observer is asked to provide a numerical score quantifying his confidence as to whether an image contains a diagnostic marker or not. Such scores are then used to measure the observers' diagnostic accuracy, summarized by the receiver operating characteristic (ROC) curve and the area under ROC curve. These types of human studies are difficult to arrange, costly, and time consuming. In addition, human observers involved in this type of study should be experts on the image genre to avoid inconsistent scoring through the lengthy study. In two-alternative forced choice (2AFC) studies, known to be faster, two images are compared simultaneously and a single indicator is given. Unfortunately, the 2AFC approach cannot lead to a full ROC curve or a set of image scores. The aim of this work is to propose a methodology in which multiple rounds of the 2AFC studies are used to re-estimate an image confidence score (a.k.a. rating, ranking) and generate the full ROC curve. In the proposed approach, we treat image confidence score as an unknown rating that needs to be estimated and 2AFC as a two-player match game. To achieve this, we use the ELO rating system, which is used for calculating the relative skill levels of players in competitor-versus-competitor games such as chess. The proposed methodology is not limited to ELO, and other rating methods such as TrueSkillTM, Chessmetrics, or Glicko can be also used. The presented results, using simulated data, indicate that a full ROC curve can be recovered using several rounds of 2AFC studies and that the best pairing strategy starts with the first round of pairing abnormal versus normal images (as in the classical 2AFC approach) followed by a number of rounds using random pairing. In addition, the proposed method was tested in a pilot human observer study. These pilot results indicate that three to five rounds of 2AFC studies require less human observer time than a full scoring study and that the re-estimated ROC curves and associated area under ROC curve values have high statistical agreement with the full scoring study. PMID- 26866044 TI - Formyl-methionine as a degradation signal at the N-termini of bacterial proteins. AB - In bacteria, all nascent proteins bear the pretranslationally formed N-terminal formyl-methionine (fMet) residue. The fMet residue is cotranslationally deformylated by a ribosome-associated deformylase. The formylation of N-terminal Met in bacterial proteins is not strictly essential for either translation or cell viability. Moreover, protein synthesis by the cytosolic ribosomes of eukaryotes does not involve the formylation of N-terminal Met. What, then, is the main biological function of this metabolically costly, transient, and not strictly essential modification of N-terminal Met, and why has Met formylation not been eliminated during bacterial evolution? One possibility is that the similarity of the formyl and acetyl groups, their identical locations in N terminally formylated (Nt-formylated) and Nt-acetylated proteins, and the recently discovered proteolytic function of Nt-acetylation in eukaryotes might also signify a proteolytic role of Nt-formylation in bacteria. We addressed this hypothesis about fMet-based degradation signals, termed fMet/N-degrons, using specific E. coli mutants, pulse-chase degradation assays, and protein reporters whose deformylation was altered, through site-directed mutagenesis, to be either rapid or relatively slow. Our findings strongly suggest that the formylated N terminal fMet can act as a degradation signal, largely a cotranslational one. One likely function of fMet/N-degrons is the control of protein quality. In bacteria, the rate of polypeptide chain elongation is nearly an order of magnitude higher than in eukaryotes. We suggest that the faster emergence of nascent proteins from bacterial ribosomes is one mechanistic and evolutionary reason for the pretranslational design of bacterial fMet/N-degrons, in contrast to the cotranslational design of analogous Ac/N-degrons in eukaryotes. PMID- 26866049 TI - Active monitoring of formaldehyde diffusion into histological tissues with digital acoustic interferometry. AB - The preservation of certain labile cancer biomarkers with formaldehyde-based fixatives can be considerably affected by preanalytical factors such as quality of fixation. Currently, there are no technologies capable of quantifying a fixative's concentration or the formation of cross-links in tissue specimens. This work examined the ability to detect formalin diffusion into a histological specimen in real time. As formaldehyde passively diffused into tissue, an ultrasound time-of-flight (TOF) shift of several nanoseconds was generated due to the distinct sound velocities of formalin and exchangeable fluid within the tissue. This signal was resolved with a developed digital acoustic interferometry algorithm, which compared the phase differential between signals and computed the absolute TOF with subnanosecond precision. The TOF was measured repeatedly across the tissue sample for several hours until diffusive equilibrium was realized. The change in TOF from 6-mm thick ex vivo human tonsil fit a single-exponential decay ([Formula: see text]) with rate constants that varied drastically spatially between 2 and 10 h ([Formula: see text]) due to substantial heterogeneity. This technology may prove essential to personalized cancer diagnostics by documenting and tracking biospecimen preanalytical fixation, guaranteeing their suitability for diagnostic assays, and speeding the workflow in clinical histopathology laboratories. PMID- 26866050 TI - Forward-scatter and side-scatter dataset for epithelial cells from touch samples analyzed by flow cytometry. AB - 'Touch' or trace biological samples submitted to caseworking labs as evidence often contain biological material from multiple individuals which can result in mixed DNA profiles. These mixture profiles are difficult to interpret and may cause analytical bottlenecks for forensic laboratories. The data in this brief reports the variation in the relative abundance of intact epithelial cells deposited by four different donors across nine days. Touch samples were generated each day by rubbing a polypropylene tube with both hands for five minutes. Forward-scatter area (FSC-A) and side-scatter area (SSC-A) data was acquired with the BD FACSCantoTM II Analyzer. The relative abundance of different sub populations within the FSC-A and SSC-A plots was calculated against the total number of events analyzed in each sample. Mean and standard deviation values were calculated for each donor. PMID- 26866051 TI - Data on Na,K-ATPase in primary cultures of renal proximal tubule cells treated with catecholamines. AB - This data article is concerned with chronic regulation of Na,K-ATPase by catecholamines. After a chronic treatment, inhibition of Na,K-ATPase activity was observed in cultures with dopamine, while a stimulation was observed in cultures treated with norepinephrine. Following a chronic incubation with guanabenz, an alpha adrenergic agonist, an increase in Na,K-ATPase alpha and beta subunit mRNAs was observed. This data supports the research article entitled, "Renal proximal tubule Na, K-ATPase is controlled by CREB regulated transcriptional coactivators as well as salt inducible kinase 1" (Taub et al. 2015) [1]. PMID- 26866052 TI - Expression, purification, crystallization and X-ray data collection for RAS and its mutants. AB - This article expands on crystal structure data for human H-RAS with mutations at position Y137, briefly described in a paper on the effects of phosphorylation of Y137 by ABL kinases (Tyrosine phosphorylation of RAS by ABL allosterically enhances effector binding, published in the FASEB Journal [1]). The crystal structures of the Y137E mutant (phosphorylation mimic) and of the Y137F mutant (without the hydroxyl group where phosphorylation occurs) were deposited in the Protein Data Bank with PDB codes 4XVQ (H-RAS(Y137E)) and 4XVR (H-RAS(Y137F)). This article includes details for expression and purification of RAS and its mutants with no affinity tags, in vitro exchange of guanine nucleotides, protein crystallization, X-ray data collection and structure refinement. PMID- 26866053 TI - Neonatal mitochondrial abnormalities due to PINK1 deficiency: Proteomics reveals early changes relevant to Parkinson's disease. AB - Parkinson's disease (PD), the second most common neurodegenerative disorder, affects roughly 7-10 million people worldwide. A wide array of research has suggested that PD has a mitochondrial component and that mitochondrial dysfunction occurs well in advance of the clinical manifestation of the disease. Previous work by our lab has categorized the mitochondrial disorder associated with Parkinson's disease in a PINK1 knockout rat model. This model develops Parkinson's disease in a spontaneous, predictable manner. Our findings demonstrated PINK1-deficient rats at 4 months of age had mitochondrial proteomic and functional abnormalities before the onset of Parkinsonian symptoms (6 months) such as the movement disorder, loss of midbrain dopaminergic neurons, or the progressive degeneration present at 9 months. With this in mind, our group investigated the PINK1 knockout genetic rat model at postnatal day 10 to determine if the observed alterations at 4 months were present at an earlier time point. Using a proteomic analysis of brain mitochondria, we identified significant mitochondrial proteomic alterations in the absence of mitochondrial functional changes suggesting the observed alterations are part of the mitochondrial pathways leading to PD. Specifically, we identified differentially expressed proteins in the PINK1 knockout rat involved in glycolysis, the tricarboxylic acid cycle, and fatty acid metabolism demonstrating abnormalities occur well in advance of the manifestation of clinical symptoms. Additionally, 13 of the differentially expressed proteins have been previously identified in older PINK1 knockout animals as differentially regulated suggesting these proteins may be viable markers of the PD pathology, and further, the abnormally regulated pathways could be targeted for therapeutic interventions. All raw data can be found in Supplementary Table 1. PMID- 26866055 TI - Realistic Numerical and Analytical Modeling of Light Scattering in Brain Tissue for Optogenetic Applications(1,2,3). AB - In recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka-Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings. Here, we introduce and study two modified approaches for modeling the distributions of light emanating from a multimode fiber and scattering through tissue, using both realistic numerical Monte Carlo simulations and an analytical approach based on the beam-spread function approach. We demonstrate a good agreement of the new methods' predictions both with recently published data, and with new measurements in mouse brain cortical slices, where our results yield a new cortical scattering length estimate of ~47 um at lambda = 473 nm, significantly shorter than ordinarily assumed in optogenetic applications. PMID- 26866054 TI - Chemokine (C-C Motif) Receptor 2 Mediates Dendritic Cell Recruitment to the Human Colon but Is Not Responsible for Differences Observed in Dendritic Cell Subsets, Phenotype, and Function Between the Proximal and Distal Colon. AB - BACKGROUND & AIMS: Most knowledge about gastrointestinal (GI)-tract dendritic cells (DC) relies on murine studies where CD103+ DC specialize in generating immune tolerance with the functionality of CD11b+/- subsets being unclear. Information about human GI-DC is scarce, especially regarding regional specifications. Here, we characterized human DC properties throughout the human colon. METHODS: Paired proximal (right/ascending) and distal (left/descending) human colonic biopsies from 95 healthy subjects were taken; DC were assessed by flow cytometry and microbiota composition assessed by 16S rRNA gene sequencing. RESULTS: Colonic DC identified were myeloid (mDC, CD11c+CD123-) and further divided based on CD103 and SIRPalpha (human analog of murine CD11b) expression. CD103-SIRPalpha+ DC were the major population and with CD103+SIRPalpha+ DC were CD1c+ILT3+CCR2+ (although CCR2 was not expressed on all CD103+SIRPalpha+ DC). CD103+SIRPalpha- DC constituted a minor subset that were CD141+ILT3-CCR2-. Proximal colon samples had higher total DC counts and fewer CD103+SIRPalpha+ cells. Proximal colon DC were more mature than distal DC with higher stimulatory capacity for CD4+CD45RA+ T-cells. However, DC and DC-invoked T-cell expression of mucosal homing markers (beta7, CCR9) was lower for proximal DC. CCR2 was expressed on circulating CD1c+, but not CD141+ mDC, and mediated DC recruitment by colonic culture supernatants in transwell assays. Proximal colon DC produced higher levels of cytokines. Mucosal microbiota profiling showed a lower microbiota load in the proximal colon, but with no differences in microbiota composition between compartments. CONCLUSIONS: Proximal colonic DC subsets differ from those in distal colon and are more mature. Targeted immunotherapy using DC in T-cell mediated GI tract inflammation may therefore need to reflect this immune compartmentalization. PMID- 26866056 TI - Cortical Transformation of Spatial Processing for Solving the Cocktail Party Problem: A Computational Model(1,2,3). AB - In multisource, "cocktail party" sound environments, human and animal auditory systems can use spatial cues to effectively separate and follow one source of sound over competing sources. While mechanisms to extract spatial cues such as interaural time differences (ITDs) are well understood in precortical areas, how such information is reused and transformed in higher cortical regions to represent segregated sound sources is not clear. We present a computational model describing a hypothesized neural network that spans spatial cue detection areas and the cortex. This network is based on recent physiological findings that cortical neurons selectively encode target stimuli in the presence of competing maskers based on source locations (Maddox et al., 2012). We demonstrate that key features of cortical responses can be generated by the model network, which exploits spatial interactions between inputs via lateral inhibition, enabling the spatial separation of target and interfering sources while allowing monitoring of a broader acoustic space when there is no competition. We present the model network along with testable experimental paradigms as a starting point for understanding the transformation and organization of spatial information from midbrain to cortex. This network is then extended to suggest engineering solutions that may be useful for hearing-assistive devices in solving the cocktail party problem. PMID- 26866059 TI - Participation in HIV cure-related research: a scoping review of the proxy literature and implications for future research. AB - OBJECTIVE: To identify the main types of HIV cure-related strategies and examine possible risks (and benefits) associated with participating in HIV cure-related research studies. METHODS: We undertook a scoping review to first map out the landscape of HIV cure-related research and then examined the risks and potential benefits associated with participating in HIV cure research. Given the early stage of many HIV cure-related studies, we used proxy literatures from non-cure HIV research and cancer research in order to anticipate possible motivators and deterrents of participation in HIV cure-related studies. RESULTS: We discussed four main categories of HIV cure-related research: (1) early antiretroviral treatment (ART); (2) latency-reversing agents (LRAs); (3) therapeutic vaccinations and immune-based therapies (IBT); and (4) stem-cell transplantation and gene therapy. At this juncture, these categories of HIV cure-related research have substantial individual risks and negligible individual and clinical benefits. Non-cure HIV research (including HIV prevention and treatment) and cancer research have empirical similarities (and differences) to HIV cure research and may provide an opportunity to anticipate ethical and logistical challenges associated with HIV cure-related research participation and decision making. Learning from the cancer field, a strong foundation of patient participant and clinician-researcher trust will need to be established to facilitate recruitment of participants into HIV cure-related studies. CONCLUSION: Further empirical social science and ethics research will be necessary to inform clinical HIV cure-related research. The study of participation in HIV cure related research can gain insights from proxy fields by incorporating study elements to clearly explain motivators and deterrents to participation and to inform the implementation of HIV cure-related studies. Study-specific contexts from the reviewed literature further demonstrate the importance of various types of research to assess factors affecting participation in HIV cure-related research, including adequate formative and ethics research. PMID- 26866057 TI - Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice(1,2,3). AB - Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca(2+) influx and desensitizes alpha4beta2*-type nicotinic receptors, reduced amphetamine seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following abstinence and a subsequent drug challenge. PMID- 26866060 TI - Treatment strategies for Middle East respiratory syndrome coronavirus. AB - Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations. PMID- 26866058 TI - Nociceptor Sensitization Depends on Age and Pain Chronicity(1,2,3). AB - Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite the greater burden of chronic pain on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months old) and aged (>18 months old) mice exhibited prominent pain behaviors during both acute (2 day) and chronic (8 week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (AM) fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following two important findings: (1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury; and (2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive. PMID- 26866061 TI - A PET/CT Directed, 3D Ultrasound-Guided Biopsy System for Prostate Cancer. AB - Prostate cancer affects 1 in 6 men in the USA. Systematic transrectal ultrasound (TRUS)-guided biopsy is the standard method for a definitive diagnosis of prostate cancer. However, this "blind" biopsy approach can miss at least 20% of prostate cancers. In this study, we are developing a PET/CT directed, 3D ultrasound image-guided biopsy system for improved detection of prostate cancer. In order to plan biopsy in three dimensions, we developed an automatic segmentation method based wavelet transform for 3D TRUS images of the prostate. The segmentation was tested in five patients with a DICE overlap ratio of more than 91%. In order to incorporate PET/CT images into ultrasound-guided biopsy, we developed a nonrigid registration algorithm for TRUS and PET/CT images. The registration method has been tested in a prostate phantom with a target registration error (TRE) of less than 0.4 mm. The segmentation and registration methods are two key components of the multimodality molecular image-guided biopsy system. PMID- 26866062 TI - [Comment on "1-year outcomes after transfemoral transcatheter or surgical aortic valve replacement. Results from the Italian OBSERVANT study"]. AB - BACKGROUND: There is a paucity of prospective and controlled data on the comparative effectiveness of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in a real-world setting. OBJECTIVES: This analysis aims to describe 1-year clinical outcomes of a large series of propensity-matched patients who underwent SAVR and transfemoral TAVR. METHODS: The OBSERVANT (Observational Study of Effectiveness of SAVR-TAVI Procedures for Severe Aortic Stenosis Treatment) trial is an observational prospective multicenter cohort study that enrolled patients with aortic stenosis (AS) who underwent SAVR or TAVR. The propensity score method was applied to select 2 groups with similar baseline characteristics. All outcomes were adjudicated through a linkage with administrative databases. The primary endpoints of this analysis were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at 1 year. RESULTS: The unadjusted enrolled population (N = 7,618) included 5,707 SAVR patients and 1,911 TAVR patients. The matched population had a total of 1,300 patients (650 per group). The propensity score method generated a low-intermediate risk population (mean logistic EuroSCORE 1:10.2 +/-9.2%+/ 7.1%, SAVR vs. transfemoral TAVR; p = 0.104). At 1 year, the rate of death from any cause was 13.6% in the surgical group and 13.8% in the transcatheter group (hazard ratio [HR]: 0,99%; 95% confidence interval [CI]: 0.72 to 1.35; p = 0.936). Similarly, there were no significant differences in the rates of MACCE, which were 17.6% in the surgical group and 18.2% in the transcatheter group (HR: 1.03; 95% CI: 0.78 to 1.36; p = 0.83). The cumulative incidence of cerebrovascular events, and rehospitalization due to cardiac reasons and acute heart failure was similar in both groups at 1 year. CONCLUSIONS: The results suggest that SAVR and transfemoral TAVR have comparable mortality, MACCE, and rates of rehospitalization due to cardiac reasons at 1 year. The data need to be confirmed in longer term and dedicated ongoing randomized trials. PMID- 26866063 TI - Treatment of Cervicogenic Headache: New Insights on the Treatment of Pain in the Neck. PMID- 26866064 TI - Acute Myelopathy in a 68-Year-Old Male. PMID- 26866065 TI - Preface. PMID- 26866066 TI - Lexical support for phonetic perception during nonnative spoken word recognition. AB - Second language comprehension is generally not as efficient and effective as native language comprehension. In the present study, we tested the hypothesis that lower-level processes such as lexical support for phonetic perception are a contributing factor to these differences. For native listeners, it has been shown that the perception of ambiguous acoustic-phonetic segments is driven by lexical factors (Samuel Psychological Science, 12, 348-351, 2001). Here, we tested whether nonnative listeners can use lexical context in the same way. Native Hebrew speakers living in Israel were tested with American English stimuli. When subtle acoustic cues in the stimuli worked against the lexical context, these nonnative speakers showed no evidence of lexical guidance of phonetic perception. This result conflicts with the performance of native speakers, who demonstrate lexical effects on phonetic perception even with conflicting acoustic cues. When stimuli without any conflicting cues were used, the native Hebrew subjects produced results similar to those of native English speakers, showing lexical support for phonetic perception in their second language. In contrast, native Arabic speakers, who were less proficient in English than the native Hebrew speakers, showed no ability to use lexical activation to support phonetic perception, even without any conflicting cues. These results reinforce previous demonstrations of lexical support of phonetic perception and demonstrate how proficiency modulates the use of lexical information in driving phonetic perception. PMID- 26866067 TI - Newborn Screening for Severe Combined Immunodeficiency: Changing the Landscape of Pediatric Primary Immunodeficiencies. PMID- 26866068 TI - Retraction notice to "Submicrometer particles and their effects on the association between air temperature and mortality in Brisbane, Australia". PMID- 26866069 TI - Reflections: Neurology and the Humanities. Mistaken identity. PMID- 26866070 TI - Author response. PMID- 26866071 TI - The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: too big to fail? PMID- 26866072 TI - Author response. PMID- 26866073 TI - Guest Editorial: Enabling Technologies for Parkinson's Disease Management. PMID- 26866074 TI - A Tribute to Joan (Jan) Mary Anderson 12 May 1932 - 28 August 2015. PMID- 26866075 TI - 'Ten Commandments' of 2015 ESC Guidelines for diagnosis and management of pericardial diseases. PMID- 26866076 TI - The Russian National Congress of Cardiology 2015. PMID- 26866078 TI - Professor Christoph Bode. PMID- 26866077 TI - Germany's largest heart centre. PMID- 26866079 TI - Professor Franz-Josef Neumann. PMID- 26866080 TI - NUTRITION STATUS AND ASSOCIATED MORBIDITY RISK FACTORS AMONG ORPHANAGE AND NON ORPHANAGE CHILDREN IN SELECTED PUBLIC PRIMARY SCHOOLS WITHIN DAGORETTI, NAIROBI, KENYA. AB - BACKGROUND: Most of the nutritional surveys that have been carried out in Kenya have concentrated on children aged five years and below who are under the care of their parent(s). The HIV/AIDS, conflict, natural disasters, endemic diseases such as malaria and tuberculosis and rising poverty has claimed the health and lives of millions of productive adults, leaving their children orphaned and vulnerable. This has led to mushrooming of orphanages to take care of these orphans and vulnerable children in Kenya. OBJECTIVE: Compare the nutrition status and associated risk factors of primary school children living in orphanages and those not living in orphanages in selected public primary schools in Dagoretti Division, Nairobi. DESIGN: Descriptive cross sectional survey. SETTING: Four public primary schools in Dagoretti Division. Data were collected from school registers and directly questioning the students, parents/guardians or caretakers. SUBJECTS: Four hundred and sixteen, four to eleven year olds randomly selected orphanage and non-orphanage children who attended the same primary school. RESULTS: The orphanage children had a significantly higher rate of stunting and underweight (p < 0.05) than the non-orphanage children. The orphanage children had also a significantly higher rate of morbidity (p < 0.05) than the non orphanage children. The orphanage children were more than three times more likely to take inadequate calories compared to the non-orphanage children. CONCLUSIONS: The main factors associated with the higher rate of malnutrition among orphanage children were high morbidity rate, inadequate amounts and diversity of foods served, low rates of vaccination and basic hygiene. PMID- 26866081 TI - IMMUNISATION TRAINING NEEDS IN MALAWI. AB - OBJECTIVES: The Malawi Ministry of Health (MOH) and its immunisation partners conducted a training needs assessment in May 2013 to assess the current status of immunisation training programmemes in health training institutions, to identify unmet training needs, and to recommend possible solutions for training of health workers on a regular basis. DESIGN: A cross-sectional, descriptive study. SETTING: Health training institutions in Malawi, a developing country that does not regularly update its curricula to include new vaccines and management tools, nor train healthcare workers on a regular basis. SUBJECTS: Researchers interviewed Malawi's central immunisation manager, three zonal immunisation officers, six district officers, 12 health facility immunisation coordinators, and eight principals of training institutions. RESULTS: All health training institutions in Malawi include immunisation in their preservice training curricula. However, the curriculum is not regularly updated; thus, the graduates are not well equipped to provide quality services. In addition, the duration of the training curriculum is inadequate, and in-service training sessions for managers and service providers are conducted only on an ad hoc basis. CONCLUSION: All levels of Malawi's health system have not met sufficient training needs for providing immunisations, and the health training institutions teach their students with outdated materials. It is recommended that the training institutions update their training curricula regularly and the service providers are trained on a regular basis. PMID- 26866082 TI - EFFECTIVENESS AND SAFETY OF 2-HOURLY 20 MCG ORAL MISOPROSTOL SOLUTION COMPARED TO STANDARD INTRAVENOUS OXYTOCIN IN LABOUR INDUCTION DUE TO PRE-LABOUR RUPTURE OF MEMBRANES AT TERM: A RANDOMISED CLINICAL TRIAL AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Pre-labour rupture of membranes (PROM) at term is a common event whose management varies from centre to centre. The practice at the Kenyatta National Hospital (KNH) for patients with PROM at term is to initiate delivery of the patient soon on admission with intravenous oxytocin, if there are no contraindications to vaginal delivery. However, in PROM at term, if the cervix is not ripe, vaginal administration of prostaglandin pessaries for cervical ripening is not possible when there is active draining of liquor, thus use of intravenous oxytocin may take a very long time or fail all together. Oral misoprostol at low doses has been found to be a safe and effective agent for labour induction in numerous studies carried out in the developed world, where there are better resources for monitoring of labour. None of the studies has been carried out in Kenya, a limited resource country. Therefore, there is a need to determine the effectiveness and safety of oral misoprostol solution at the KNH, a limited resource set up. OBJECTIVE: To determine the effectiveness and safety of 2-hourly 20 mcg oral misoprostol solution compared to the standard intravenous oxytocin in labour induction in mothers with pre-labour rupture of membranes at term at the Kenyatta National Hospital. DESIGN: An unblinded randomised clinical trial. SETTING: Kenyatta National Hospital Labour Ward Unit. PARTICIPANTS: Eighty three pregnant women with pre-labour rupture of membranes at term without an indication for Caeserian section were consented and randomised for labour induction with either oral misoprostol at a dose of 20mcg 2-hourly up to a maximum of 4-doses, or with intravenous oxytocin according to the WHO protocol. MAIN OUTCOME MEASURES: Induction to delivery interval; maternal complications and early neonatal outcomes. RESULTS: The overall induction success rates in the misoprostol arm was 81% versus 83% in the oxytocin arm (P = 0.447). The mean induction to vaginal delivery interval in the misoprostol arm was 8.4 hours as compared to 9.45 hours in the oxytocin arm (P = 0.116). The induction to active labour interval was similar in the two study arms. The mean induction to active labour in the misoprostol arm was 4.02 hours as versus 4.51 hours in the oxytocin arm (P = 0.223 ). Two women who had failed induction with misoprostol were augmented with oxytocin and delivered vaginally. The Caesarean section rates were 19% in the misoprostol arm and 17% in the oxytocin arm (P = 0.447), which was not statistically significant. The maternal outcomes were similar in the two study arms. Four women had tachysystole in the misoprostol arm, compared to three in the oxytocin arm (P = 0.253). In the misoprostol arm two women had hypertonus compared to three in the oxytocin arm (P = 0.322).There was one case of hyperstimulation in the misoprostol arm and two in in the oxytocin arm. There were no differences in the foetal/neonatal outcomes. No baby had an Apgar score of less than seven at one or five minutes. No baby was admitted to the New Born Unit in either of the two arms. There was no case of a still birth in either of the study arms. There was no significant difference in the passage of meconium between the two arms, 39% in the misoprostol arm and 35.7% in the oxytocin arm (P = 0.755). The passage of meconium did not impact on the neonatal outcomes. CONCLUSION: Oral misoprostol solution 20mcg 2-hourly is as safe and effective as the standard intravenous oxytocin for labour induction in women presenting with prelabour rupture of membranes at term at the Kenyatta National Hospital. PMID- 26866083 TI - MUSCULOSKELETAL PRESENTATION OF MULTIPLE MYELOMA AT GENERAL HOSPITAL DOUALA, CAMEROON. AB - Background: very little is known about musculoskeletal features of multiple myeloma (MM) in Africa. OBJECTIVES: To describe the musculoskeletal features of multiple myeloma at presentation in a tertiary health care centre in sub-Saharan Africa. DESIGN: A Cross sectional observational study. SETTING: The Douala General Hospital, Cameroon from 2007 to 2013. SUBJECTS: A patient was said to have MM according the current international consensus criteria for diagnosis and staging of MM. Patients with monoclonal gammopathy of undetermined significance, solitary plamocytoma and other haematologic malignancies were excluded. RESULTS: A total of 62 patients were diagnosed with multiple myeloma, 63% were female. Mean age was 57 +/- 12,1 (19-81) years. Musculoskeletal presentation included spine bone pains (75.6%); vertebral fracture with spinal cord compression in 46.8 %. Other clinical features at presentation included anaemia (70.93%), and nephropathy (17.74%). The average percentage of bone marrow plasmacytosis at diagnosis was 33% and Immunoglobulin G was found in 86% of patients. Sixty three per cent of patients were diagnosed at stage III of the disease. CONCLUSION: Presence of bone pain and anaemia should alert the clinician to investigate along the lines of multiple myeloma. Majority of the patients have osteolytic lesions and pathologic fractures at the time of diagnosis. PMID- 26866084 TI - RHEUMATOID ARTHRITIS ASSOCIATED WITH PULMONARY FIBROSIS IN NIGERIANS: TWO CASE REPORTS. AB - Rheumatoid arthritis may sometimes present with extra-articular involvement, pulmonary involvement is not common. Rheumatoid arthritis has been reported among Nigerians and extra-articular manifestations are rarely seen. One of the patients was misdiagnosed and mismanaged as a patient with pulmonary tuberculosis. The study is to demonstrate that rheumatoid arthritis is not as rare as previously reported in Nigeria and its pulmonary involvement can mimic tuberculosis or other granulomatous lung disorder. Clinical and serological acumen are necessary to distinguish between the two. Two diagnosed patients with rheumatoid arthritis and pulmonary involvement seen at Olabisi Onabanjo University Teaching Hospital (OOUTH), are hereby presented. PMID- 26866085 TI - PATTERNS OF POISONING AMONG PATIENTS AGED 0-13 YEARS AT A PAEDIATRIC HOSPITAL IN NAIROBI. AB - OBJECTIVES: To determine the pattern of poisoning amongst patients admitted at a paediatric hospital in Nairobi and compare it with that of other hospitals around the world DESIGN: A retrospective hospital based multivariate study. SETTING: Gertrude's Garden Children's Hospital, Nairobi, Kenya. SUBJECTS: Medical records of all children admitted with a diagnosis of poisoning between January 2003 and December 2007. RESULTS: The age range of the study population was birth to 13 years. The mean age was 3.57 years with a standard deviation of +/- 1.57 with a peak incidence in the one to three years old age group (56.7%). Males comprised 61.7% of the cases. The most common cause of poisoning was ingestion of a drug ( 46.7%). Petroleum products caused 30.0%, detergents 8.3% and organophosphates 6.7%. Ninety six point seven percent of poisonings were unintentional and 93.3% of injuries took place at home. There were no mortalities. CONCLUSION: The majority of these incidents were preventable. Measures need to be instituted to reduce the number of incidents of poisoning in children. This can take the form of health and safety education particularly in relation to storage of common household poisons. PMID- 26866086 TI - PREVALENCE AND ASSOCIATED CHARACTERISTICS OF CYTOMEGALOVIRUS (CMV) IMMUNOGLOBULIN ANTIBODIES AMONG BLOOD DONORS AT A UNIVERSITY TEACHING HOSPITAL IN NIGERIA. AB - BACKGROUND: The screening for cytomegalovirus (CMV) specific antibodies is not routine in our setting, thus the transfusion of blood portends high risk for susceptible individuals. OBJECTIVE: To determine the prevalence of IgG and IgM specific antibodies and associated characteristics in blood donors seen at a referral teaching hospital in Nigeria. DESIGN: Prospective, cross-sectional and descriptive study. SETTING: Blood Bank and Serology Unit of the Department of Haematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife, Nigeria. SUBJECTS: One hundred and eighty four blood donors negative for human immunodeficiency virus, hepatitis B and C viruses and syphilis were assessed for their levels of CMV specific IgG and IgM antibodies (AccuDiagTM ELISA, DIAGNOSTIC AUTOMATION INC, USA) using the enzyme linked immunosorbent assay technique (ELISA). RESULTS: Ninety six percent of the donors were males while those with secondary education and below (61.3%), unmarried (70%), artisans and unemployed including students (82.5%) were in the majority. The prevalence of CMV IgG and IgM antibodies were 97.4% and 52.6%, while CMV IgG antibody range from 94.7% to 100% in all types of donation. All female donors (3.8%) were positive for IgG and IgM antibodies. The level of education of the donors predicts IgM antibody positivity, those with secondary education or less are more likely than others to be positive (p < 0.05; X2 = 15.98). Linear logistic regression showed that male donors and those in the artisan group are more likely to be positive for IgM antibody (p < 0.05). CONCLUSION: The prevalence of CMV antibodies is very high (IgG = 97.4%; IgM = 52.6%) in our setting. Donors with low educational status and artisans are more likely to be IgM positive. Therefore, a more stringent donor selection, adoption of leukodepleted blood and blood products for uninfected patients especially the immuno-compromised and adoption of a national policy on CMV infected blood is advocated. PMID- 26866087 TI - BARRIERS TO UPTAKE OF BREAST CANCER SCREENING IN KENYA. AB - OBJECTIVES: To conduct clinical breast cancer screening in three sites in Western Kenya and explore community barriers to screening uptake. DESIGN: Cross-sectional study. SETTING: Western Kenya specifically, Mosoriot, Turbo, and Kapsokwony. SUBJECTS: Community members (18 years and older) who did not attend the screening events. OUTCOME MEASURE: The outcome measure was having heard about the breast cancer screening events. Both structured and open-ended questions were used for data collection. Item frequency, correlations, and content analyses were performed. RESULTS: A total of 733 community members were surveyed (63% women, median age 33 years, IQR = 26-43). More than half (55%) of respondents had heard about the screening but did not attend. The majority of those who had heard about this particular screening had knowledge of screening availability in general (45% vs. 25%, p < 0.001). Only 8.0% of those who heard and 6.0% of those who had not heard of the screening event had previously undergone clinical breast exam (p = 0.20). Reasons for not attending the screening event were personal factors, including busy schedule (41.0%), perceived low personal risk (12.7%), lack of transport (4.2%), as well as health facility factors such as poor publicity (14.4%) and long queues (8.7%). CONCLUSION: Barriers to breast cancer screening uptake were associated with inadequate publicity, perceived long waits at event and busy lives among community women. PMID- 26866088 TI - FEMALE GENITAL TRACT CANCERS IN SAGAMU, SOUTHWEST, NIGERIA. AB - OBJECTIVE: To describe pattern of female genital tract cancers seen at Olabisi Onabanjo University Teaching Hospital (OOUTH), Sagamu, Nigeria. DESIGN: This is a retrospective review of all cases of female genital tract cancers managed at the Gynaecology department of OOUTH, Sagamu, Nigeria. SETTING: OOUTH is a tertiary health institution of the State's university and it takes referrals from within and outside the State. SUBJECTS: Case records of all female genital tract cancers managed between January 2004 and December 2013 were retrieved and analysed using SPSS version 16.0. RESULTS: There were 2059 women treated forvarious gynaecologic conditions, 179 (8.7%) were cases of female genital tract cancers and 161 records were available for analysis. Cervical cancer constituted the commonest (51.6%), followed by ovarian (35.4%), endometrial (9.9%), and choriocarcinoma (1.9%). There were no cases of vaginal and fallopian tube cancers. The lowest mean age was found in choriocarcinoma (36.60 +/- 4.50 years) and highest in vulvar cancer (70.00 +/- 2.82 years). The mean ages for cervical, endometrial and ovarian cancers were (51.98 +/- 12.39), (65.38 +/- 7.24), and (54.42 +/- 10.51) years respectively. Similarly the least mean parity was found in choriocarcinoma (2.33 +/- 1.52), and the highest in vulvar cancer (6.00 +/- 1.44). The mean parity for cervical, endometrial, and ovarian were (4.10 +/- 1.49),(3.06 +/- 1.48), and (3.72 +/- 1.68) respectively. These differences are statistically significant, age; F = 7.61, p < 0.0001, and parity; F = 3.27, p= 0.013. CONCLUSION: Incidence of cervical, endometrial, and ovarian cancers remain high and presentations are at late stages. There is a need to improve on cervical cancer screening, and for the attending physicians to improve on their indices of suspicions as regards endometrial and ovarian cancers. PMID- 26866089 TI - FACTORS INFLUENCING VOLUNTARY MEDICAL MALE CIRCUMCISION AMONG MEN AGED 18-50 YEARS IN KIBERA DIVISION. AB - BACKGROUND: Voluntary Medical Male Circumcision (VMMC) is the surgical removal of all or part of the foreskin from the penis. It is done for medical reasons as it has been shown to reduce the risk of female to male transmission of HIV by up to 60%. It has also been associated with lower transmission of sexually transmitted infections. Voluntary Medical Male Circumcision services have been scaled up in countries with high prevalence, generalised heterosexual HIV epidemics and low rates of male circumcision. Kibera is inhabited by a multi-ethnic community with a sizeable number of un-circumcising ethnic groups. OBJECTIVES: To determine the uptake of voluntary medical male circumcision among men in Kibera Division and to identify factors associated with circumcision preference. DESIGN: Descriptive cross-sectional study. SETTING: Kibera Division of Nairobi County. SUBJECTS: Simple random sampling was used to enrol 387 participants. A 42-item questionnaire was administered to the participants for determining the uptake of VMMC. It had three sub-sections: demographic characteristics, general knowledge about VMMC and AIDS and acceptability of VMMC, which collected data on the main outcome measures. Data captured was entered into EpiInfo and converted to Stata13 for validation and analysis. Bivariate statistics were generated for all the variables in accordance to the study questions. Categorical variables were analysed using chi-square tests, while the qualitative variables were analysed using the t-test. Multivariate logistic regression analysis was performed to identify factors associated with the acceptability of male circumcision. RESULTS: The study analysed data for a sample of 341 individuals whose mean age was 31 years (95% = 31 +/- 9.1) and 62% were married. A total of 54% of the respondents had completed secondary and tertiary level of education. The level of understanding about VMMC was above average. Fifty nine percent of the respondents (95% CI = 0.54-0.64) knew about VMMC. Of these, 31% had obtained information about VMMC from TV and radio. The most frequently mentioned reason for undergoing VMMC was prevention of HIV and sexually transmitted infections. The level of uptake of VMMC was high at 75%. The study established that the prefered age group for circumcision was during adolescence. Using multivariate logistic regression, the factors associated with uptake of VMMC were education level, medical and hygiene reasons for VMMC. Barriers for uptake were cost, pain and long recovery period after the operation. CONCLUSION: The uptake and acceptability of male circumcision is high among the general population in Kibera. Participant understanding of HIV and VMMC was also high. There is need for heightened awareness creation in educational institutes. This will specifically target young men before or shortly after their sexual debut when they may still be free of HIV and HSV-2 infections. Circumcision by medical providers should be increased in traditionally circumcising regions to reduce incidence of adverse events. PMID- 26866090 TI - DISASTER PREPAREDNESS IN SECONDARY SCHOOLS IN RUIRU DIVISION, KIAMBU COUNTY, KENYA. AB - OBJECTIVE: To establish common disasters, preparedness and management in secondary school in Ruiru Division, Kiambu County, Kenya. DESIGN: Descriptive cross-sectional study. SUBJECTS: Out of the target population a hundred and twenty (120) respondents were selected from the students, teachers and the support staff. Eighteen key informants snowballed gave information that augmented the study findings. RESULTS: The respondents did not know how to use the first aid kit elements (= 835.263, p = 0.000, df = 1). Lack of knowledge on use of first aid elements was significantly high among the respondents which also reflected lack of skills to manage minor incidences (= 835.1, P = 0.000, df = 1). The respondents confessed the lack of preparedness for disasters in their schools (= 840.8, P = 0.0, df = 2). CONCLUSIONS: The study was set to find out the Preparedness for disasters in ruirusecondary with an aim of filling any gap that maybe found by implementing strategies to improve preparedness for ruriru people which should be the way to go everywhere and those in authority to avail the required resources for disaster management. PMID- 26866091 TI - A STUDY OF SOME MORPHOGENETIC TRAITS AMONG THE ESAN ETHNIC GROUP OF NIGERIA. AB - BACKGROUND: Genetic variability is a common feature of many organisms. The existence of genetic variation in man is caused by many factors along with selection, migration, gene flow and genetic drift. Human genetics are known as hereditary traits, these hereditary traits include the dominant and recessive traits in humans. Most of the genes are transmitted in the Mendelian pattern and a few are transmitted through the non-Mendelian pattern. OBJECTIVE: To show variation pattern in earlobe attachment, hair line distribution and presence or absence of cheek dimples and to determine prevalence of these traits among the Esan ethnic group of Southern Nigeria. DESIGN: Descriptive study. SETTING: The target populations for this study are the Esan ethnic group of Southern Nigeria. Esan land is bordered to the south by Benin City, to the east by Agbor City, to the north by Etsako and to the west by River Niger. SUBJECT: A simple random sampling technique was used to select 400 volunteered subjects (176 males, 224 females). They were between the ages of 17-60. Their parents and grandparents were from Esan backgrounds. Data on cheek dimple (present or absent), widow's peak or straight hairline and earlobe attachment was gathered. RESULT: Results showed 12.5% of Males and 21.3% of females had cheek dimples while 31.5% of males and 34.7% of female had no dimple. 29.0% Males and 40.0% females had unattached earlobe while 15.0% Males and 16.0% females had their earlobes attached. Results for widow's peak showed 14.7% males and 16.5% females had widow's peak while 29.3% males and females 39.5% didn't have a peak. The chi-squared analysis of variance showed that there is a no significant difference between gender for earlobe attachment, hair line variation and cheek dimple (p > 0.05). CONCLUSION: The study concluded that these traits varies in the population but do not vary with gender. PMID- 26866092 TI - ATYPICAL TUBERCULOSIS PRESENTING WITH PRIMARY INFERTILITY AND ENDOMETRIAL CALCIFICATION. AB - Tuberculosis (TB) is caused by mycobacterium tuberculosis. It remains a public health concern especially in developing country. Pulmonary infection is the main presentation. However, genitourinary TB is common especially with the increase in Human Immunodeficiency virus (HIV) infection. Genitourinary TB is one of the most common causes of extrapulmonary tuberculosis which affects 12% patients with pulmonary tuberculosis. It is common in women less than 40 years of age and rarely occurs in post-menopausal. Therefore it is more likely to affect women in reproductive years leading to infertility. Fallopian tube involvement in genital TB is at least 95-100% of cases and is mainly from haematological spread and this leads to infertility. This is a case of a woman who presented a diagnosis of primary infertility and tuberculous endometritis with endometrial calcification. PMID- 26866093 TI - AN UNUSUAL CASE OF RECTAL FOREIGN BODY: CASE REPORT. AB - Foreign bodies within the rectum are an infrequent occurrence with a wide variety of objects either inserted or swallowed. Many techniques of removal have been described to remove these objects in case series mainly in developed countries. We report a case of unusually large rectal foreign body we managed by sigmoidotomy with primary closure. PMID- 26866094 TI - PARENTS' AND HEALTHCARE PROVIDERS PERSPECTIVES ABOUT HOSPITALISED CHILDREN BEING VISITED BY OTHER CHILDREN IN NAIROBI, KENYA. AB - BACKGROUND: Throughout history, visitation of the hospitalised child has always been restricted. The subject of whether hospitalised children should be visited by other children has been accorded minimal attention. OBJECTIVE: To determine the current status of visitation of the hospitalised children and the parents and healthcare providers'views on hospitalised children being visited by other children. DESIGN: A descriptive study carried out using quantitative and qualitative methods in two phases SETTING: All paediatric wards at Kenyatta National Hospital and Gertrudes Children's Hospital. SUBJECTS: Nurses, paediatricians and parents of hospitalised children. RESULTS: A total of 161 parents participated in phase I of the study whereas 11 nurses not specialised in paediatric nursing, 13 paediatric nurses, 12 nurse managers, fur paediatricians and13 parents participated in phase II of the study. The study established that visiting of the hospitalised child by family members especially children aged below twelve years is severely restricted particularly in the public hospital. Despite this, however, majority of the healthcare providers and the parents acknowledged the importance of the hospitalised children being visited by other children. This is because it promotes healing, gives the sick child psychological satisfaction and relieves anxiety in the hospitalised child, the accompanying parent and the other children. The risk of exposing the visiting children to infection was cited as the main reason for the restrictions. CONCLUSION: Both the healthcare providers and the hospitalised children's parents appreciate the importance of the hospitalised child being visited by other children. There is a need to review healthcare policies to make provision for hospitalised children to be visited by other children. PMID- 26866095 TI - FLUCONAZOLE AND BORIC ACID FOR TREATMENT OF VAGINAL CANDIDIASIS--NEW WORDS ABOUT OLD ISSUE. AB - OBJECTIVE: To compare boric acid as an effective treatment for VVC compared to fluconazole. We also studied the efficiency of these drugs in preventing recurrence of VVC. DESIGN: A cross sectional, randomized, double-blind study. SETTINGS: Gynaecology clinic of Imam Reza hospital, Tehran - Iran SUBJECTS: Women with signs and symptoms related to Vulvo Vaginal Candidiasis. RESULTS: Seventy five patients out of total 150 patients with signs and symptoms related to Vulvo Vaginal Candidiasis were treatedwith boric acidpowder everynight for a week and the remaining 75 patients received Fluconazole. The cure rate in first group was 46.7% but the cure rate in second group was 37.3%. The difference was not statistically significant (P>0.3). Difference between the efficacy of the two drugs was not significant either (P=0.47). The recurrence rate among patients in first group was 35% while it was 32% in second group. Their difference was not statistically significant (P=0.54). CONCLUSION: According to our findings, treatment of vaginal candidiasis with boric acid is as effective as fluconazole. The availability of boric acid and its relatively low cost suggests it as a safe and effective drug for treatment of candidiasis. PMID- 26866096 TI - RISK OF RED BLOOD CELL ALLOIMMUNISATION IN RWANDA: ASSESSMENT OF PRETRANSFUSION CROSSMATCH TECHNIQUES USED IN DISTRICT HOSPITALS. AB - BACKGROUND: Screening of alloantibodies in patients is not yet done in district hospitals of Rwanda. The practice is to transfuse ABO/D compatible blood following an immediate spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM). OBJECTIVES: To assess the risk of red blood cell (RBC) alloimmunisation associated with the use of IS-XM compared to the IAT-XM in patients receiving blood transfusions in district hospitals in Rwanda. DESIGN: A cross-sectional comparative descriptive study. SETTING: Four Rwandan district hospitals. Kirehe and Nyanza hospitals used IS-XM while Muhima and Ruhengeri hospitals used IAT-XM. SUBJECTS: Blood samples were obtained from 187 patients (101 with IS-XM and 86 with IAT-XM) transfused in January, February, October, and November of 2012. RESULTS: The median age of blood recipients was 31 years (7 - 80) and 36% of them were male. Sixteen specific antibodies were identified in 12 patients: anti-RH1/D (2),anti-RH2/C (2), anti-RH3/E (2), anti-RH4/c (1), anti RH5/e (2),anti-LE1/Lea (2),anti-JK1/Jka (1), anti-JK2/Jkb (1), anti-KEL1/K (1), anti-MNS1/M (1), and autoantibody (1).The global prevalence of redblood cell (RBC) alloimmunisationwas 6.4% (12/187). Thatprevalence was significantly higher in the IS-XM group (10.4%) than in the IAT-XM group (2.3%) with an odds ratio of 4.8; [95% CI=1.2-19.8]; and a p-value of 0.031. CONCLUSION: The prevalence of red blood cell (RBC) alloimmunisation in 187 patients receiving blood transfusions was 6.4% and was higher in recipients from hospitals using IS-XM, with Rhesus (RH) system antibodies widely predominant (56.2%).We recommend that IAT-XM be used in all district hospitals in Rwanda to minimise this risk. PMID- 26866097 TI - GLOBAL DISPARITY IN CHILDHOOD DENTAL CARIES: IS THERE A REMEDY? AB - OBJECTIVE: To determine risk factors associated with childhood caries, their association withthe widening childhood caries gap between developed and less developed nations and proposition on how the gap could be bridged. DATA SOURCE: Pubmed database was used to retrieve appropriate research literature. STUDY SELECTION: All publications in the English language reporting on prevalence, management strategies and policy matters relating to childhood dental caries for the period 2000 to 2011. DATA SYNTHESIS: The data collected were analysed and the results related to the objective of the study. CONCLUSION: Socio-economic factors, educational factors and human resource factors were found have been associated with childhood caries gap between the developed and less developed nations. The caries gap could be bridged through smart policies by less developed nations, involving multiple strategies geared towards preventive oral health care. PMID- 26866098 TI - RELAPSING FEVER, A DISAPPEARING CAUSE OF FEVER AND MATERNAL DEATH IN SENGEREMA, TANZANIA, EAST AFRICA. AB - OBJECTIVE: To study the incidence of tick borne relapsing fever (TBRF) during the last 50 years, once like malaria an endemic disease in Sengerema, Tanzania. DESIGN: By analyzing the annual reports, focusing on the number of admissions, maternal deaths, blood smears of patients with fever for Borrelia. SETTING: Sengerema district, Tanzania. SUBJECT: Admissions in Sengerema Hospital due to TBRF. MAIN OUTCOME MEASURES: From 1960 to 2010, we analyzed the incidence of TBRF. RESULT: Forty annual admissions in the sixties/seventies, 200 in the eighties (range from 37 in 1964 to 455 in 1988), dropping to 30 in the nineties. For the last nine years no Borrelia spirochetes were found in blood smears at the laboratory anymore and no admissions for TBRF were registered. The number of maternal deaths due to relapsing fever decreased simultaneously; the last one recordedwas in 2002. CONCLUSION: During the last century, we have witnessed the disappearing of tick borne relapsing fever in Sengerema. Increase of gold mining, improved local economy, housing and standards of living after the nineties resulted in an almost complete eradication of the incidence of TBRF. PMID- 26866099 TI - CALCINOSIS CUTIS - A SERIES OF 59 CONSECUTIVE CASES CONFINED AMONG WOMEN. AB - BACKGROUND: Calcinosis cutis is the cutaneous deposition of calcium salts. Tumoral Calcinosis is a condition consisting of massive subcutaneous deposits of calcium salts often overlying large joints in otherwise healthy patients. OBJECTIVE: To describe the characteristics of a series of patients with Tumoral Calcinosis in the Gurage Zone of Central Ethiopia. METHODOLOGY: Data was collected from 59 patients who presented with clinical diagnosis of calcinosis cutis around hip region between January 2005 and January 2009. RESULTS: All cases were females, with a mean (standard deviation) age at diagnosis of 50.7(10.8). The duration of illness ranged from one to eighteen years. The cases were distributed in the different villages of Gurage Zone without any sign of clustering of cases. The lesions were localized around hip region on both sides. The patients did not have any related co-morbidity or any history of similar illness among close family members. None of the patients gave history of evident trauma to the site of the lesions. Significant proportion of the patients (53.4%) confirmed to carry water container and/or other goods on their side. Serum Phosphate and Calcium levels in selected patients were with in normal limit. Histo-pathological examinations of five cases revealed Calcium deposits in collagenous connective tissue. CONCLUSION: The lesion was found to be relatively common in the study area and specifically confined to females. The probable factor associated with the cases is carrying objects on their side (hip area). Further research with in-depth clinical and laboratory evaluation is of paramount importance. PMID- 26866100 TI - PREVALENCE AND INTENSITY OF SINGLE AND MIXED SCHISTOSOMA MANSONI AND SCHISTOSOMA HAEMATOBIUM INFECTIONS IN PRIMARY SCHOOL CHILDREN IN RACHUONYO NORTH DISTRICT, HOMABAY COUNTY, WESTERN KENYA. AB - OBJECTIVE: To determine the prevalence andintensity of single and mixed schistosomiasis infection among primary school children in Rachuonyo North District, Homabay County in western Kenya. DESIGN: A descriptive cross sectional study. SETTING: A parasitological survey involving six primary schools in Rachuonyo North District, Homabay County. SUBJECTS: Four hundred and seventy four(474) school children, seven to 15 years old. Each child provided a urine and stool sample for diagnosis of schistosome and soil-transmitted helminth infections. Urine samples were processed using the filtration technique and the sample examined by microscopy for Schistosoma haematobium ova. Stool samples were processed by the Kato-Katz technique and the sample examined by microscopy for ova of S. mansoni and soil-transmitted helminths. RESULTS: Prevelance of S.haematobium was 37.6%, S.mansoni (12.2%), hookworm (14.6%), Ascaris lumbricoides (6.3%), Trichuris trichiura (5.3%) among the children in the participating schools. Overall, 78.6% of the children infected with S.haematobium had light infection (<50 eggs per 10 ml of urine) and the rest (21.4%) had heavy infection (50 eggs per 10 ml of urine). On the hand, 75.9% of those with S.mansoni had light infection (one to 99 eggs per gram of stool (EPG), and the rest (24.1%) had moderate infection intensities (100-399 (EPG). CONCLUSION: This is the first report in which both S.haematobium and S.mansoni are found together in the same geographic locality in high prevalence in the Lake Victoria region of western Kenya, with S. haematobium being the most predominant in some places. Rachuonyo North District becomes a new focus of mixed human schistosome infections in Kenya. The significant burden of schistosomiasis in this area highlights the need to include regular treatment for schistosomiasis in the national school based deworming programme especially now that the infection occurs in areas more than five kilometres away from the lake. PMID- 26866101 TI - ACUTE LEUKEMIAS IMMUNOPHENOTYPES AT AGAKHAN UNIVERSITY HOSPITAL, NAIROBI. AB - OBJECTIVE: The aim was to determine relative frequencies of acute leukemia immunophenotypes using commonly expressed markers and to describe the clinicopathological characteristics. Design: This was a prospective cross sectional study. SETTING: The study was based at Aga khan clinical laboratory department. SUBJECTS: One hundred and thirty two (132) consecutive blood and bone marrow specimens from patients suspected to have acute leukemia were analysed for cytomorphological characteristics and immunophenotyping. The clinical pathological characteristics were also recorded. Immunological category was assigned using the EGIL criteria. RESULTS: There were 88 AML and 42 ALL patients analysed for immunophenotypes. Only tw cases of biphenotypic leukemia were found. The commonest overall AML morphological sub-type was AML-M2, 26 (29.5%). Majority of ALL cases were B-cell immunological sub-type (96.6%). Early pre-B phenotype constituted 62.07% and Common B-cell ALL 37.93%. There were only 4 cases of T cell ALL. Majority of patients presented with anaemia with a median hemoglobin of 7.5g/dl (range 2-15g/dl). The median platelet count was 55 (range 4-462 x 10(9)/L). CONCLUSION: Immunophenotyping of acute leukemia is beneficial in accurate diagnosis of patients with these malignancies in this setup. T-cell ALL, AML-M6 and M7 are less frequent than what has been reported in most studies in Africa. PMID- 26866102 TI - AWARENESS AND PRACTICE ON BIOMEDICAL WASTE MANAGEMENT AMONG HEALTH CARE PERSONNEL IN KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: The proper handling and disposal of Bio-medical waste (BMW) is very imperative. There are well defined set rules for handling BMW worldwide. Unfortunately, laxity and lack of adequate training and awareness in execution of these rules leads to staid health and environment apprehension. OBJECTIVE: To assessthe awareness and practice regarding biomedical waste management among health care personnel in Kenyatta National Hospital (KNH) DESIGN: A cross sectional study design. SETTING: Kenyatta National Hospital SUBJECTS: Doctors, Nurses and support staff who have worked in the institution for more than six months and consented were evaluated. RESULTS: The total level of awareness on biomedical waste management among health care personnel was found to be 60%. The doctors scored 51% which was the lowest score the nurses scored 65% which was the highest score while the support staff scored 55%. As for the practices, the results showed that most of the healthcare personnel were aware of the biomedical waste management practices in the hospital with the lowest scores emerging from doctors and this shows no association between knowledge on biomedical waste management and education. When asked how they would describe the control of waste management in the institution 59% said good and 40% said fair while 1% said poor. CONCLUSION: The present study therefore outlines the gap between biomedical waste management rules and inadequate state of execution and awareness in practice. It is recommended that enhancement be done to the already existing Hospital Infection Control Committee to supervise all the aspects of biomedical waste management. Periodical training programmes for biomedical waste handling and disposal to the staff with focus on doctors is highlighted. PMID- 26866103 TI - EFFECTS OF STANDARD AND/OR GLUTAMINE DIPEPTIDE AND/OR OMEGA-3 FATTY ASCID SUPPLEMENTED PARENTERAL NUTRITION ON NEUTROPHIL FUNCTIONS, INTERLEUKIN-8 LEVEL AND LENGTH OF STAY--A DOUBLE BLIND,CONTROLLED, RANDOMISED STUDY. AB - BACKGROUND AND AIMS: Protein calorie malnutrition for cancer patients is related with altered cellular and humoral immunity. Standard TPN and glutamine and lipid emulsion with omega 3 fatty acids were given to colorectal cancer patients and the effects of these to neutrophil functions and IL-8 levels are compared. METHODS: Consecutive 36 patients with colorectal cancer diagnosed with endoscopic biopsy and with malnutrition determined by subjective global assessment were enrolled to study. The patients are randomly divided into four groups. Standard TPN to control group, TPN with glutamine solution to S-D group, TPN with omega 3 fatty acid solution to S-O group and TPN with omega 3 fatty acids solution and glutamine to S-D-O group were given for seven days after the operation. At the preoperative, postoperative first day and 7th day, neutrophil phagocytosis index, neutrophil adhesivity index and IL-8 levels were determined. RESULTS: In all groups compared to control group neutrophil phagocytosis index were increased significantly (p<0.05). The most increasing was in group 3. There wasn't significant difference between groups about postoperative first day neutrophil adhesiveness index (p>0.05). At the 7th day the neutrophil adhesivity index for study groups were increased compared with control group, but there was no significant differences between groups. There was no significant difference between groups for IL-8 levels. CONCLUSIONS: As a result of the study, altered cellular immunity in colorectal cancer patients with malnutrition can be corrected with omega 3 fatty acid emulsions and glutamine added to TPN so the ratio of morbidity and mortality can be decreased. PMID- 26866104 TI - LEFT VENTRICULAR INFLOW OBSTRUCTION BY GIANT ATRIAL SEPTAL ANEURYSM IN A NEONATE WITH HYPOPLASTIC RIGHT HEART SYNDROME: CASE REPORT. AB - Atrial septal aneurysm remains a rare congenital cardiac malformation. In the neonatal age group it can occur as an isolated cardiac malformation or in association with complex hypoplastic cardiac malformations of the right and left heart. In the adult population most aneurysms have been described in association with stroke. Baby H.N delivered on 10/05/2008 by C/S, was cyanosed at birth with systemic desaturation. Chest X-ray showed oligaemic lung fields while two dimensional echocardiograms showed tricuspid atresia with hypoplastic right ventricle, large secundum atrial septal defect, and highly mobile gigantic aneurysms of the atrial septum obstructing the inflow of the mitral valve and entering the left ventricle in diastole. Surgical intervention was not possible and child died on second day. PMID- 26866105 TI - MOLECULAR CHARACTERISATION AND ANTIMICROBIAL RESISTANCE PATTERNS OF ESCHERICHIA COLI ISOLATES FROM GOATS SLAUGHTERED IN PARTS OF KENYA. AB - OBJECTIVE: To determine the antibiotic resistance patterns of pathogenic Escherichia coli on goat meat carcass at Huruma and Kiserian abattoirs in Kenya. DESIGN: Laboratory based study. SETTING: Huruma and Kiserian abattoirs in Kenya, SUBJECTS: 400 slaughtered goats inspected by veterinary health officers and approved for human consumption. METHODS: A Total of 400 slaughtered goats which were inspected by veterinary health officers and approved for human consumption were sampled from Huruma and Kiserian abattoir. Goat carcass swabs were collected by passing each swab tissue on four parts of the carcass mainly neck, right and left forelimbs, right and left hind limbs, and brisket. RESULTS: A total of 54 E. coli isolates were isolated and confirmed to be pathogenic. The percentage of isolates resistant to various microbial agents was recorded as follows: ampicillin (26 %), amoxycillin-clavulanic acid (17%), tetracycline (15%), chroramphenicol (4%), and ceftrixone (2% each). All Escherichia coli isolates were susceptible to gentamicin sulphamethaxazole-trimethomprin, kanamycin, cetriazididine (CAZ, 30pg), ciproxacin, nalidixic acid and chloramphenicol. Isolates were resistant to one or more of the antibiotics tested. Among the drugs tested, resistance was more frequently observed against ampicillin, amoxycillin clavulanic acid, tetracycline, ceftrixone and chroramphenicol antibiotics. Among the isolates 26(48%) were positive for the stx1 gene, 19(35%) had the eae gene, 10(19%) possessed est gene,while 8(15%) harboured elt gene. Overall five isolates (10%) possessed aspu gene and two (4%) had aggR gene. No isolate possessed ipah gene. CONCLUSION: This study demonstrated that there is a significant level of antimicrobial resistance in pathogenic E. coli isolated from goat meat from Huruma and Kiserian abattoir. This indicates that goat meat from abattoirs could pose a risk of transmission of pathogenic antibiotic resistant strains to human. Poor hygienic standards and indiscriminate use of antimicrobials are the two main reasons for the presence of resistant pathogens in goat carcasses. RECOMMENDATIONS: Implemention of appropriate hygiene measures to control contamination of meat with pathogenic E. coli. PMID- 26866106 TI - FETAL OUTCOMES AMONG GRAND MULTIPAROUS AND MULTIPAROUS WOMEN IN MULAGO HOSPITAL, UGANDA. AB - OBJECTIVE: To compare fetal outcomes among grand multiparous (para 5-9) and multiparous (para 2-4) delivering in Mulago hospital, Uganda. DESIGN: Prospective cohort study. SETTING: Mulago hospital, Uganda. SUBJECTS: One hundred and fifty six grand multiparous and multiparous women were recruited on admission in labourward and followedup through labour and immediate postpartum period. Fetal outcomes among the two groups were collected and analyzed. RESULTS: The admissions to SCU were similar in the two groups i.e. 11(7%) GMP vs. 11(7%) MP, the number of fresh still births was higher among the grandmultiparas 13(8.3%) GMP vs. 7(4.5%) MP though this was not statistically significant. The fetal weight did not significantly differ in the two groups. CONCLUSION: There was no difference in fetal outcomes among GMPs when compared to MPs. PMID- 26866107 TI - ATTITUDES AND ACCEPTANCE OF NIGERIANS TOWARDS VASECTOMY--A COMPARISON OF MARRIED MEN AND WOMEN IN LAGOS. AB - BACKGROUND: Nigeria with a growth rate of 28%, accounts for over two thirds of the West African population. It also has one of the highest maternal mortality rates in the world with contraceptive prevalence among married couples less than 10%. Despite its safety and efficacy vasectomy appears to be unpopular in our environment. OBJECTIVE: To assess the perception and acceptance of married men and women towards vasectomy and the influence of the spouse on the man's decision to accept or reject vasectomy. DESIGN: A cross sectional questionnaire based study. SETTING: With an estimated population of 20 million, Lagos is the most cosmopolitan and urbanised city in Nigeria and accounts for 65% of all commercial activities in the country. Virtually all the tribes in Nigeria are represented in the city. SUBJECTS: Literate pregnant women recruited from the antenatal clinics and literate new fathers. All subjects were recruited from three health facilities in the Lagos metropolis. RESULTS: Twenty seven point five and twenty one percent of the men and women respectively had a good Knowledge of vasectomy while 49.1% and 19% of all men and women respectively with good knowledge would accept vasectomy (or agree for their spouses to have the procedure). Overall acceptance rates for men and women were 26 and 13.5% respectively while 92% of men who can opt for vasectomy will only do so if their spouses agree. Knowledge about vasectomy was the strongest single factor influencing the acceptance of vasectomy (p= 0.013) with stronger correlation among men than women (p=0.005 vrs p=.0.023). CONCLUSION: Knowledge and acceptance of vasectomy is significantly better in males than female Nigerians living in Lagos. PMID- 26866108 TI - REASSESSMENT OF HELMINTH INFECTIONS IN GULU MUNICIPALITY NOTHERN UGANDA AFTER THE TWENTY YEARS OF INSURGENCY: USING THREE DIAGONOSTIC METHODS TO COMPARE THEIR SENSITIVITY. AB - BACKGROUND: During the period of insurgency there were several internally displace people camps all over the Northern Uganda. People who lived within ten kilometers from Gulu Municipality were forced to evacuate their villages and re locate and build huts for themselves in areas identified for them by the government. There were several of such camps within the municipality creating influx of people from the villages to the municipality for security. Now with the situation restored to normal, there is need to re-assess and update information on the prevalence of helminth infections in Gulu municipality where many of the internally displaced people (IDP) settled. OBJECTIVE: To find out if S. mansoni and soil transmitted nematode infections are so prevalent and very common in children aged betweenfive to 20 years. In Gulu municipality and that additional preventive and curative measure need to be considered. Further is there a strong need to reconsider more sensitive diagnostic methods at the hospitals or does the standard approach of direct smear examination recognise at least most heavy infected children with any of the parasites. Setting. The study was carried out in Gulu municipality. DESIGN: Purposive and random sampling methods were used. Study Population: Mainly Primary school children aged between five to 20 years randomly selected from four primary schools purposively selected around Gulu municipality were recruited for the study. For control 20 staff of each school randomly selected were also studied. RESULTS: Of the 582 samples tested, 117(20.1%) were found positive for Schistosoma mansoni. Fifteen (2.6%) other samples were found positive for other helminths like Ascaris lumbricoides, Trichuris trichiura H.nana Hookworm. The comparison between the methods showed that the results obtained by the three methods were similar for field research. There is a low intensity of infection with soil transmitted helminths found in the primary schools around Gulu municipality. CONCLUSION: We concluded that the prevalence and intensity of infection with soil transmitted helminths was low among the children aged between 5 to 20 years in the four primary school studied (2.6%) but there was medium infection with S.mansoi (20.1%). The sensitivity in detecting the helminthes eggs in the stool specimen were similar. Though the original Kato/Katz method recorded lowest egg count than the Polderman and Odongo Aginya methods. This could be due to the fact that the slides were read immediately. PMID- 26866109 TI - RICKETS IN RURAL KENYAN PRESCHOOL CHILDREN: CASE REPORT. AB - Clinical rickets has not been reported previously in Embu district, Kenya. Baseline clinical assessments performed for a nutrition intervention study in preschool children (n=324) identified 28 cases of rickets (8.6% of study sample). Clinical characteristics included: delays of sitting, walking, and teething; bone and chest deformities; widened wrists and ankles; and bowed lower extremities. Risk factors identified were short duration of breastfeeding with feeding of cereal-based supplements with little or no milk, low calcium intake, limited sunlight exposure. Vitamin D and calcium deficiencies likely contributed to these cases. Treatment with Vitamin D3 and milk resulted in clinical improvement. PMID- 26866110 TI - THE INCIDENCE AND RISK FACTORS FOR INTRA-OPERATIVE HYPOTHERMIA AMONG PAEDIATRIC PATIENTS UNDERGOING GENERAL ANAESTHESIA AT THE KENYATTA NATIONAL HOSPITAL. AB - OBJECTIVE: To determine the incidence and risk factors for intra-operative hypothermia in paediatric patients undergoing general anaesthesia at the Kenyatta National Hospital. DESIGN: A prospective observational study. SETTING: The Kenyatta National Hospital main operating theatres and affiliated satellite operating theatres. SUBJECTS: A total of 100 paediatric patients (range; three days to 12 years, mean; 4.1 +/- 3.3 years) were enrolled in the study. RESULTS: Thirty out of 100 patients developed hypothermia defined as a core temperature < 36 degrees C recorded at least once during provision of general anaesthesia. Ninety percent of those developing hypothermia were male compared to 63% who remained normothermic (p = 0.006). Proportionally, more than twice as many hypothermic patients had a caudal block (43% versus 20%, p = 0.016) and received 121 ml more of fluid (p = 0.002) compared to the normothermic group. The patients who became hypothermic tended to be colder at induction of anaesthesia (36.6 +/- 0.5 degrees C versus 37.0 +/- 0.5 degrees C, p = < 0.0001) but there was no significant difference in the waiting time, time of induction, environmental temperatures or theatre temperatures compared to those not developing hypothermia. There was no significant difference in the BMI between the two groups (14.0 +/- 2.9 kg/ m2 versus 15.2 +/- 3.5 kg/m2, p = 0.101). CONCLUSION: The incidence of intra-operative core hypothermia in paediatric patients undergoing general anaesthesia at the Kenyatta National Hospital is 30%. Gender (male), lower body temperature at induction, use of caudal block and the volume of intravenous fluids infused were significant independent predictors of core hypothermia. The most significant predictor was body temperature at the time of induction of general anaesthesia. PMID- 26866111 TI - ANATOMICAL SITES OF COLORECTAL CANCER IN A SEMI-URBAN NIGERIAN HOSPITAL: IS THERE A TRUE RIGHTWARD SHIFT. AB - BACKGROUND: Recent report on colorectal tumours in Nigeria and Africa sub-region from big urban cities have shown that the incidence of colorectal cancer is rising and with a proportionate right-ward shift. OBJECTIVE: To assess the sub site distribution and surgical treatmentpatterns of colorectal cancer in a semi urban tertiary Nigerian hospital. DESIGN: A retrospective descriptive study. SETTING: Tertiary health institution in a semi-urban (rural) community. SUBJECTS: All consecutive in-patients, admitted and managed for acute intestinal obstruction due to colorectal cancer. MAIN OUTCOME: The right colon was the site of predilection (60.6%) while the left colon was only (6.06%). Young adults were mostly affected. RESULT: A total of thirty three (33) cases of colorectal cancer (CRC) were seen during the study period. There were 20 (60.6%) males and 13 (39.4%) females. The male:female ratio was 1.5:1. The age range was between 22-87 years (mean 57.09 years). The peak age of occurrence was the 6th decade. All patients'were symptomatic at presentation. The caccum (36.365) was the predominant site affected; followed by the rectum (24.24%) and the hepatic flexure (21.21%). Of the colonic tumours, 60.6% were on the right colon while only 6.06% were on the left colon. Tumours of the descending and sigmoid colon were conspicuously absent. Fifteen patients (45.5%) had curative resection and 33.3% had palliative surgery. Twenty one point two percent mortality was recorded, while 21.2% refused surgery and opted for alternative care. CONCLUSION: Colorectal cancers are seen among rural dwellers in Nigeria. Presentations are often late. The right colon is the dominant site affected; this calls for a change in strategy for formulating a preventive policy for the country. PMID- 26866112 TI - DETERMINANTS OF MATERNAL MORTALITY AMONG WOMEN OF REPRODUCTIVE AGE ATTENDING KISII GENERAL HOSPITAL, KISII CENTRAL DISTRICT, KENYA (JANUARY 2009-JUNE 2010). AB - OBJECTIVE: To describe the causes and determinants of maternal mortality among women of reproductive age seeking healthcare services at Kisii General Hospital. DESIGN: Descriptive retrospective study. SETTING: Kisii General Hospital which is a Level-5 Referral Hospital. SUBJECTS: Seventy-two women who had died as a result of pregnancy and childbirth related conditions who had sought obstetric services at Kisii General Hospital. RESULTS: Majority 51(70.8%) of deceased did not go to hospital promptly, due to; lack of transport 22 (30.6%), lack of money 17 (23.6%), and hospital distance 8 (11.1%). About 43 (60%) of those who died were between 15-25 years of age. Hospital experiences included; delay in service provision by staff 14 (19.4%), unavailability of blood for transfusion 6 (8.3%), and lack of money for drugs 12 (16.7%). Complications which led to maternal mortality were mainly; postpartum sepsis, bleeding, hypertension and cardiovascular conditions. CONCLUSION: Lack of lack of transport, inability to pay, delayed care seeking and lack of emergency obstetrics were the major challenges. Postpartum sepses, bleeding and pre-eclampsia were the leading complications that led to death. PMID- 26866113 TI - HE BURDEN AND CHALLENGES OF NEONATAL TETANUS IN KILIFI DISTRICT, KENYA--2004-7. AB - OBJECTIVES: To describe the incidence of neonatal tetanus (NNT) and to describe the trends between 2004 and 2007; to show the geographical distribution of NNT in Kilifi district and to describe routine immunisation coverage, catch-up campaigns and mop-ups. DESIGN: Retrospective study SETTING: Kilifi district, Coastal Kenya SUBJECTS: Children diagnosed with Neonatal Tetanus (NNT) attending Health facilities in the District. RESULTS: The incidence of NNT in Kilifi increased from 0.6 in 2004 to 1.0 per 1000 live births in 2007. Over 50% of Kilifi district was a high risk area for NNT. It was a public health problem (> 1 per 1000 live births) in 19/36 locations. Immunisation (TT2+) increased from 4% in 2004 to 17% in 2007 for women of childbearing age and from 22% to 98% for pregnant women in the same period. All cases of NNT were delivered at home. 83% of NNT cases had potentially infectious materials applied to their cords. CONCLUSIONS: Neonatal tetanus was an increasing problem in Kilifi district in the period 2004-2007. Immunisation coverage was low for women of childbearing age. TT immunisation data capture was a mix-up (pregnant women andwomen of childbearing age) at various health facilities and was a challenge to accurate estimates of TT2+ immunisation coverage. PMID- 26866114 TI - PREVALENCE OF HEAD LICE INFESTATION IN PRIMARY SCHOOL CHILDREN IN PORT HARCOURT. AB - BACKGROUND: Head lice infestation affects mainly school-aged children and prevalence varies from region to region. Head lice infestation is of public health concern and screening is integrated into the School Health Programme. OBJECTIVE: To determine the prevalence of head lice infestation in primary school aged children in Port Harcourt, Nigeria. DESIGN: Cross-sectional descriptive study. SUBJECTS: A stratified multi-staged sampling technique was used to recruit pupils between six and 12 years of age, from thirteen primary schools located in three School Districts in the area. The heads of the pupils were inspected for head lice and nits with the aid of a battery operated Robi lice comb, magnifying glass and a torch as light source. RESULTS: A total of 1350 pupils were studied, 743 (55%) females and 607 (45%) males giving a female to male ratio of 1.2:1. Ten (0.7%) of the pupils had head lice infestation while five (0.4%) had evidence of past head lice infestation. The number of infested pupils among the younger age group (six to nine years) was seven (0.8%) and is higher, though not statistically significant, than that in the older age group (ten to twelve years) which was three (0.6%) (p = 0.453). No male was found to be infested while ten (1.3%) females were infested and the observed gender difference was statistically significant (p = 0.002). CONCLUSION: Head lice infestation still exists in Primary School children in Nigeria, therefore, screening for head lice infestation should still remain a part of the School Health Programme. PMID- 26866115 TI - IMPLEMENTATION OF A SCHOOL-BASED HIV PREVENTION CURRICULUM FOLLOWING NATIONAL DISSEMINATION IN NYANZA PROVINCE, KENYA. AB - BACKGROUND: Primary School Action for Better Health (PSABH) became the national HIV prevention curriculum of Kenya in 2005. OBJECTIVE: To examined implementation of PSABH and student risk behaviour s. SETTING: Muhuru, a rural division of Nyanza Province. SUBJECTS: One thousand one hundred and forty six students aged 9 21 years from six primary schools in Muhuru. OUTCOME MEASURES: Anonymous surveys were administered to assess students'exposure to PSABH curriculum components, sexual activity, condom use, and self-efficacy related to engaging in lower risk behaviours. RESULTS: The six schools implementing PSABH were not implementing the full curriculum. Fifty-five percent of males and 44% of females reported a history of sexual activity. For females, condom self-efficacy was related to lower risk behaviour, while HIV education during pastoral instruction was associated with higher risk. Boys who reported higher self-efficacy and learning about abstinence strategies engaged in lower risk behaviour , while exposure to HIV education in assemblies and communication with relatives about HIV was associated with higher risk. CONCLUSION: Previous studies documented benefits of PSABH. However, it is unclear how effective the curriculum is after national scale-up. In this community, PSABH was implemented at a low level, with some curriculum components associated with higher risk behaviour, calling into question how PSABH is being delivered. Future studies should examine effective strategies for ongoing support, monitoring, and evaluation. Successfully disseminating evidence-based prevention strategies could reduce HIV incidence and the burden on healthcare providers struggling to care for people living with HIV/AIDS. PMID- 26866116 TI - MALARIA PREVALENCE IN UNDER FIVE CHILDREN UTILISING INSECTICIDE TREATED NETS THROUGH VOUCHER SCHEME PROGRAMME IN MTWARA MUNICIPALITY. AB - OBJECTIVE: To determine the malaria prevalence in under five year old children, comparing those utilising with those not utilising insecticide treated nets in Mtwara Municipality. DESIGN: Descriptive cross-sectional study. SETTING: Five streets that were randomly selected in Mtwara Municipality. SUBJECTS: Three hundred and ninety eight (398) under five year old children. RESULTS: In the 398 under five year old children in this study, 18 (4.5%) and 20 (5.0%) tested positive by RDT and microscopy, respectively. Of the 385 who always used Insecticide Treated Nets (ITNs), 16 (4.2%) had malaria, compared to four among the 13 who rarely/or never used nets (30.8%). Thus there is a relationship between the use of the treated nets and prevalence of malaria (chi2 P-value 0.002). Inspite of the decline in malaria prevalence anaemia remain a big problem as among those 378 who tested negative for malaria, 81% had haemoglobin level below normal (8 and 11 g/dl). CONCLUSION: Malaria infection has been prevented by the ITNs in under five years children as the prevalence of malaria is only 4.2% among net users compared to 30.8% non net users. The ITNs are useful since the overall five percent prevalence of malaria is less than expected in Mtwara region which had the prevalence of 33.6 percent in 2007 and less to the overall national prevalence of seven percent in under fives in urban areas in 2009. Plasmodium falciparum species is still a notorious cause of the disease among under fives compared to other types, thus the preventive measures should scientifically target this species at large. PMID- 26866117 TI - GENDER AND AGE RELATED VARIATION IN CORNEA POWER. AB - OBJECTIVE: To determine the mean cornea power for this population and how it varies with gender and age. DESIGN: A retrospective study. SETTING: The eye clinic of the Niger Delta University Teaching Hospital. SUBJECTS: All patients referred to the Optometric unit by the duty optometrist using a Carl Zeiss 599 Auto-refractokeratometer and the findings recorded in a register designed for that purpose. These patients had previously undergone full ocular examination by the referring Ophthalmologist. STATISTICAL ANALYSIS: Data collected were analysed using the statistical package of social scientist (SPSS) version 16. RESULTS: Two hundred and one patients (402 eyes) were analysed in this study. They consisted of 100 males and 101 females (M/F = 1:1.01). Their ages ranged from 8 to 84 years with a mean of 42.74 years (SD +/- 14.62). The mean cornea power in the entire population was found to be 43.24 D (95% Cl 43.01-43.41). The horizontal cornea meridian has a higher diopteric power than the vertical meridian (43.38 D versus 43.13). The mean cornea power in females is greater than the mean cornea power in males (43.62 D versus 42.80 D). Cornea power was found to vary with age (P = 0.003), and the relationship was found to be linear on regression analysis. CONCLUSION: The diopteric power of the female cornea is higher than that of their male counterpart. There is evidence that suggests a reduction of the diopteric power of the cornea with aging, but further studies are needed to confirm this observation. PMID- 26866118 TI - CAREGIVERS' KNOWLEDGE AND HOME MANAGEMENT OF FEVER IN CHILDREN. AB - BACKGROUND: Fever is one of the most common complaints presented to the Paediatric Emergency Unit (PEU). It is a sign that there is an underlying pathologic process, the most common being infection. Many childhood illnesses are accompanied by fever, many of which are treated at home prior to presentation to hospital. Most febrile episodes are benign. Caregivers are the primary contacts to children with fever. Adequate caregivers' knowledge and proper management of fever at home leads to better management of febrile illnesses and reduces complications. OBJECTIVE: To determine the caregivers' knowledge and practices regarding fever in children. DESIGN: A cross-sectional study. SETTING: Peadiatric Emergency Unit at Kenyatta National Hospital (KNH) SUBJECTS: Two hundred and fifty caregivers of children under 12 years presenting with fever in August to October 2011 to the PEU. RESULTS: Three quarters of the caregivers' defined fever correctly. Their knowledge on the normal body was at 47.6%. Infection was cited as the leading cause of fever (95.2%). Brain damage (77.6%) and dehydration (65.6%) were viewed as the most common complication. Fever was treated at home by 97.2% of caregivers, most of them used medication. CONCLUSIONS: Fever was defined correctly by 75.2% of the study participants and a majority of them used touch to detect fever. Fever was managed at home with medications. Public Health Education should be implemented in order to enlighten caregivers on fever and advocate for the use of a clinical thermometer to monitor fever at home. PMID- 26866119 TI - PRIMARY MALIGNANT AMELANOTIC MELANOMA ARISING FROM A VITILIGO PATCH OF AN AFRICAN TANZANIAN: CASE REPORT. AB - Skin cancer is rare in people of African origin while vitiligo occurs worldwide. The occurrence of primary malignant melanoma and vitiligo together is very rare. We present a rare case of primary malignant amelanotic melanoma arising from a depigmented patch of a patient with vitiligo. It was completely excised and followed for one year. No recurrence or metastases was noted during the follow up period. PMID- 26866121 TI - Nurses and midwives stand by Rosie Batty. PMID- 26866120 TI - Detention is damaging for children. PMID- 26866122 TI - Dementia programs fall short. PMID- 26866123 TI - AHPRA watching thousands of health professionals to protect public. PMID- 26866124 TI - NSW Inquiry backs need for registered nurses in aged care. PMID- 26866125 TI - Call to boost quality palliative care in the bush. PMID- 26866126 TI - Strategy to increase number of Indigenous nurses in NT. PMID- 26866127 TI - Engaging rural and remote health leaders of tomorrow. PMID- 26866128 TI - New wound management course for healthcare professionals. PMID- 26866129 TI - CATSINaM breaks the ice on alarming drug. PMID- 26866130 TI - A FORCE to be reckoned with. A YEAR IN REVIEW. PMID- 26866131 TI - A fairer Medicare for all. PMID- 26866132 TI - Doffing and donning debate. PMID- 26866133 TI - [Comment on "1-year outcomes after transfemoral transcatheter or surgical aortic valve replacement. Results from the Italian OBSERVANT study"]. AB - BACKGROUND: There is a paucity of prospective and controlled data on the comparative effectiveness of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in a real-world setting. OBJECTIVES: This analysis aims to describe 1-year clinical outcomes of a large series of propensity-matched patients who underwent SAVR and transfemoral TAVR. METHODS: The OBSERVANT (Observational Study of Effectiveness of SAVR-TAVI Procedures for Severe Aortic Stenosis Treatment) trial is an observational prospective multicenter cohort study that enrolled patients with aortic stenosis (AS) who underwent SAVR or TAVR. The propensity score method was applied to select 2 groups with similar baseline characteristics. All outcomes were adjudicated through a linkage with administrative databases. The primary endpoints of this analysis were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at 1 year. RESULTS: The unadjusted enrolled population (N = 7,618) included 5,707 SAVR patients and 1,911 TAVR patients. The matched population had a total of 1,300 patients (650 per group). The propensity score method generated a low-intermediate risk population (mean logistic EuroSCORE 1:10.2 +/-9.2%+/ 7.1%, SAVR vs. transfemoral TAVR; p = 0.104). At 1 year, the rate of death from any cause was 13.6% in the surgical group and 13.8% in the transcatheter group (hazard ratio [HR]: 0,99%; 95% confidence interval [CI]: 0.72 to 1.35; p = 0.936). Similarly, there were no significant differences in the rates of MACCE, which were 17.6% in the surgical group and 18.2% in the transcatheter group (HR: 1.03; 95% CI: 0.78 to 1.36; p = 0.83). The cumulative incidence of cerebrovascular events, and rehospitalization due to cardiac reasons and acute heart failure was similar in both groups at 1 year. CONCLUSIONS: The results suggest that SAVR and transfemoral TAVR have comparable mortality, MACCE, and rates of rehospitalization due to cardiac reasons at 1 year. The data need to be confirmed in longer term and dedicated ongoing randomized trials. PMID- 26866135 TI - Acute Myelopathy in a 68-Year-Old Male. PMID- 26866136 TI - Preface. PMID- 26866140 TI - Reflections: Neurology and the Humanities. Mistaken identity. PMID- 26866138 TI - Newborn Screening for Severe Combined Immunodeficiency: Changing the Landscape of Pediatric Primary Immunodeficiencies. PMID- 26866141 TI - Author response. PMID- 26866143 TI - Author response. PMID- 26866145 TI - A Tribute to Joan (Jan) Mary Anderson 12 May 1932 - 28 August 2015. PMID- 26866144 TI - Guest Editorial: Enabling Technologies for Parkinson's Disease Management. PMID- 26866269 TI - The relative association between individual difference variables and general psychotherapy outcome expectation in socially anxious individuals. AB - OBJECTIVE: Although patients' psychotherapy outcome expectation relates to their treatment outcome, little is known about correlates of this expectation. Moreover, the limited research has largely assessed convenience variables as correlates, with little replication and few examinations of the relative strength of associations between the correlates and outcome expectation. This clinical analogue study examined the relation between socially anxious undergraduates' (N = 178) characteristics and their general psychotherapy outcome expectation. We investigated characteristics supported as correlates in prior studies. METHODS: Data derived from a baseline assessment prior to a larger experiment. Participants' mean level of social anxiety was within 1 standard deviation of the mean of clinical, treatment-seeking samples, and 65.2% of the sample either had therapy experience or were actively considering it. RESULTS: Participants' general outcome expectation was significantly associated with positive beliefs about and intention to seek therapy. Multivariate regression models showed a positive association between psychological mindedness (B = .59, p < .001) and outcome expectation. Subgroup analyses indicated that for participants with prior therapy experience, greater satisfaction with that treatment (B = 5.26, p < .001) was associated with higher outcome expectation. CONCLUSION: Results are discussed with regard to their implications for treatment-seeking intentions and treatment planning. PMID- 26866270 TI - Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis. AB - The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a key component of tumor necrosis factor (TNF)-induced necroptosis and plays a crucial role in necroptosis execution. However, the mechanisms that control MLKL activity are not completely understood. Here, we identify the molecular chaperone Hsp90 as a novel MLKL-interacting protein. We show that Hsp90 associates with MLKL and is required for MLKL stability. Moreover, we find that Hsp90 also regulates the stability of the upstream RIP3 kinase. Interference with Hsp90 function with the 17AAG inhibitor destabilizes MLKL and RIP3, resulting in their degradation by the proteasome pathway. Furthermore, we find that Hsp90 is required for TNF stimulated necrosome assembly. Disruption of Hsp90 function prevents necrosome formation and strongly reduces MLKL phosphorylation and inhibits TNF-induced necroptosis. Consistent with a positive role of Hsp90 in necroptosis, coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Our findings demonstrate that an efficient necrotic response requires a functional Hsp90. PMID- 26866271 TI - Affinity purification-mass spectrometry analysis of bcl-2 interactome identified SLIRP as a novel interacting protein. AB - Members of the bcl-2 protein family share regions of sequence similarity, the bcl 2 homology (BH) domains. Bcl-2, the most studied member of this family, has four BH domains, BH1-4, and has a critical role in resistance to antineoplastic drugs by regulating the mitochondrial apoptotic pathway. Moreover, it is also involved in other relevant cellular processes such as tumor progression, angiogenesis and autophagy. Deciphering the network of bcl-2-interacting factors should provide a critical advance in understanding the different functions of bcl-2. Here, we characterized bcl-2 interactome by mass spectrometry in human lung adenocarcinoma cells. In silico functional analysis associated most part of the identified proteins to mitochondrial functions. Among them we identified SRA stem-loop interacting RNA-binding protein, SLIRP, a mitochondrial protein with a relevant role in regulating mitochondrial messenger RNA (mRNA) homeostasis. We validated bcl-2/SLIRP interaction by immunoprecipitation and immunofluorescence experiments in cancer cell lines from different histotypes. We showed that, although SLIRP is not involved in mediating bcl-2 ability to protect from apoptosis and oxidative damage, bcl-2 binds and stabilizes SLIRP protein and regulates mitochondrial mRNA levels. Moreover, we demonstrated that the BH4 domain of bcl-2 has a role in maintaining this binding. PMID- 26866272 TI - Loss of Fas apoptosis inhibitory molecule leads to spontaneous obesity and hepatosteatosis. AB - Altered hepatic lipogenesis is associated with metabolic diseases such as obesity and hepatosteatosis. Insulin resistance and compensatory hyperinsulinaemia are key drivers of these metabolic imbalances. Fas apoptosis inhibitory molecule (FAIM), a ubiquitously expressed antiapoptotic protein, functions as a mediator of Akt signalling. Since Akt acts at a nodal point in insulin signalling, we hypothesize that FAIM may be involved in energy metabolism. In the current study, C57BL/6 wild-type (WT) and FAIM-knockout (FAIM-KO) male mice were fed with normal chow diet and body weight changes were monitored. Energy expenditure, substrate utilization and physical activities were analysed using a metabolic cage. Liver, pancreas and adipose tissue were subjected to histological examination. Serum glucose and insulin levels and lipid profiles were determined by biochemical assays. Changes in components of the insulin signalling pathway in FAIM-KO mice were examined by immunoblots. We found that FAIM-KO mice developed spontaneous non-hyperphagic obesity accompanied by hepatosteatosis, adipocyte hypertrophy, dyslipidaemia, hyperglycaemia and hyperinsulinaemia. In FAIM-KO liver, lipogenesis was elevated as indicated by increased fatty acid synthesis and SREBP 1 and SREBP-2 activation. Notably, protein expression of insulin receptor beta was markedly reduced in insulin target organs of FAIM-KO mice. Akt phosphorylation was also lower in FAIM-KO liver and adipose tissue as compared with WT controls. In addition, phosphorylation of insulin receptor substrate-1 and Akt2 in response to insulin treatment in isolated FAIM-KO hepatocytes was also markedly attenuated. Altogether, our data indicate that FAIM is a novel regulator of insulin signalling and plays an essential role in energy homoeostasis. These findings may shed light on the pathogenesis of obesity and hepatosteatosis. PMID- 26866275 TI - Glucose-Derived Porous Carbon-Coated Silicon Nanowires as Efficient Electrodes for Aqueous Micro-Supercapacitors. AB - In this study, we report on carbon coating of vertically aligned silicon nanowire (SiNWs) arrays via a simple hydrothermal process using glucose as carbon precursor. Using this process, a thin carbon layer is uniformly deposited on the SiNWs. Under optimized conditions, the coated SiNWs electrode showed better electrochemical energy storage capacity as well as exceptional stability in aqueous system as compared to uncoated SiNWs. The as-measured capacitance reached 25.64 mF/cm(2) with a good stability up to 25000 charging/discharging cycles in 1 M Na2SO4 aqueous solution. PMID- 26866273 TI - Cellular localization of NRF2 determines the self-renewal and osteogenic differentiation potential of human MSCs via the P53-SIRT1 axis. AB - NRF2 (nuclear factor erythroid-derived 2-like 2) plays an important role in defense against oxidative stress at the cellular level. Recently, the roles of NRF2 in embryonic and adult stem cells have been reported, but its role in maintaining self-renewal and differentiation potential remains unknown. We studied the mechanisms of NRF2 action in mesenchymal stem cells (MSCs) derived from human bone marrow. We found that the cellular localization of NRF2 changed during prolonged cell passage and osteogenic differentiation. Blocking the nuclear import of NRF2 using ochratoxin A (OTA) induced the loss of the self renewal and osteogenic potential of early-passage (EP) MSCs. Conversely, reinforcing the nuclear import of NRF2 using tert-butylhydroquinone (t-BHQ) improved the self-renewal capacity and maintained the differentiation potential in the osteogenic lineage of EP MSCs. Real-time quantitative PCR and western blot analysis showed that NRF2 positively regulates sirtuin 1 (SIRT1) at the mRNA and protein levels via the negative regulation of p53. The self-renewal and osteogenic potential suppressed in OTA-treated or NRF2-targeting small hairpin RNA (shRNA)-infected EP MSCs were rescued by introducing small interfering RNA (siRNA) targeting p53. t-BHQ treatment in late-passage (LP) MSCs, which lost their self-renewal and osteogenic potential, reversed these effects. In LP MSCs treated with t-BHQ for ~7 days, the phosphorylation and nuclear localization of NRF2 improved and SIRT1 protein level increased, whereas p53 protein levels decreased. Therefore, our results suggest that NRF2 plays an important role in regulating p53 and SIRT1 to maintain MSC stemness. This study is the first to establish a functional link between NRF2 and SIRT1 expression in the maintenance of MSC self-renewal and differentiation potential. PMID- 26866276 TI - Highlighting material structure with transmission electron diffraction correlation coefficient maps. AB - Correlation coefficient maps are constructed by computing the differences between neighboring diffraction patterns collected in a transmission electron microscope in scanning mode. The maps are shown to highlight material structural features like grain boundaries, second phase particles or dislocations. The inclination of the inner crystal interfaces are directly deduced from the resulting contrast. PMID- 26866274 TI - Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model. AB - The treatment of breast cancer-induced osteolysis remains a challenge in clinical settings. Here, we explored the effect and mechanism of combined treatment with zoledronic acid (ZA) and plumbagin (PL), a widely investigated component derived from Plumbago zeylanica, against breast cancer-induced osteoclastogenesis. We found that the combined treatment with PL and ZA suppressed cell viability of precursor osteoclasts and synergistically inhibited MDA-MB-231-induced osteoclast formation (combination index=0.28) with the abrogation of recombinant mouse receptor activator of nuclear factor-kappaB ligand (RANKL)-induced activation of NF-kappaB/MAPK (nuclear factor-kappaB/mitogen-activated protein kinase) pathways. Molecular docking suggested a putative binding area within c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk) protease active sites through the structural mimicking of adenosine phosphate (ANP) by the spatial combination of PL with ZA. A homogeneous time-resolved fluorescence assay further illustrated the direct competitiveness of the dual drugs against ANP docking to phosphorylated JNK/Erk, contributing to the inhibited downstream expression of c Jun/c-Fos/NFATc-1 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1). Then, in vivo testing demonstrated that the combined administration of PL and ZA attenuated breast cancer growth in the bone microenvironment. Additionally, these molecules prevented the destruction of proximal tibia, with significant reduction of tartrate-resistant acid phosphatase (TRAcP)-positive osteoclast cells and potentiation of apoptotic cancer cells, to a greater extent when combined than when the drugs were applied independently. Altogether, the combination treatment with PL and ZA could significantly and synergistically suppress osteoclastogenesis and inhibit tumorigenesis both in vitro and in vivo by simulating the spatial structure of ANP to inhibit competitively phosphorylation of c-Jun N-terminal kinase/extracellular signal-regulated kinase (JNK/Erk). PMID- 26866277 TI - Editorial: Endurance Exercise: An Important Therapeutic Adjuvant in the Overall Treatment of Myositis? PMID- 26866280 TI - Influence of Perfluorooctanoic Acid on the Transport and Deposition Behaviors of Bacteria in Quartz Sand. AB - The significance of perfluorooctanoic acid (PFOA) on the transport and deposition behaviors of bacteria (Gram-negative Escherichia coli and Gram-positive Bacillus subtilis) in quartz sand is examined in both NaCl and CaCl2 solutions at pH 5.6 by comparing both breakthrough curves and retained profiles with PFOA in solutions versus those without PFOA. All test conditions are found to be highly unfavorable for cell deposition regardless of the presence of PFOA; however, 7% 46% cell deposition is observed depending on the conditions. The cell deposition may be attributed to micro- or nanoscale roughness and/or to chemical heterogeneity of the sand surface. The results show that, under all examined conditions, PFOA in suspensions increases cell transport and decreases cell deposition in porous media regardless of cell type, presence or absence of extracellular polymeric substances, ionic strength, and ion valence. We find that the additional repulsion between bacteria and quartz sand caused by both acid base interaction and steric repulsion as well as the competition for deposition sites on quartz sand surfaces by PFOA are responsible for the enhanced transport and decreased deposition of bacteria with PFOA in solutions. PMID- 26866281 TI - On the feasibility of life-saving locomotive bumpers. AB - Motivated by the thousands of pedestrians killed each year in train impacts, this paper investigates the life-saving capability of four high-level locomotive bumper concepts. The head motions produced by the four concepts are modeled as one or two square acceleration pulses and are analyzed using the Head Injury Criterion (HIC). Surprisingly, the analyses show that all four concepts can achieve HIC values of less than 200 for an impact with a locomotive traveling at 100 km/h. Two of the concepts eject the pedestrian trackside with at a velocity of roughly 40 km/h and the risk of ground-impact injury is discussed in the context of related automobile accident data. The computed bumper lengths are a fraction of the overall length of a locomotive and are thus feasible for practical implementation. One concept involves an oblique impact and the potential for rotational head injury is analyzed. This basic feasibility research motivates future investigations into the detailed design of bumper shapes, multi body pedestrian simulations, and finite-element injury models. PMID- 26866282 TI - Simulative investigation on head injuries of electric self-balancing scooter riders subject to ground impact. AB - The safety performance of an electric self-balancing scooter (ESS) has recently become a main concern in preventing its further wide application as a major candidate for green transportation. Scooter riders may suffer severe brain injuries in possible vehicle crash accidents not only from contact with a windshield or bonnet but also from secondary contact with the ground. In this paper, virtual vehicle-ESS crash scenarios combined with finite element (FE) car models and multi-body scooter/human models are set up. Post-impact kinematic gestures of scooter riders under various contact conditions, such as different vehicle impact speeds, ESS moving speeds, impact angles or positions, and different human sizes, are classified and analyzed. Furthermore, head-ground impact processes are reconstructed using validated FE head models, and important parameters of contusion and laceration (e.g., coup or contrecoup pressures and Von Mises stress and the maximum shear stress) are extracted and analyzed to assess the severity of regional contusion from head-ground contact. Results show that the brain injury risk increases with vehicle speeds and ESS moving speeds and may provide fundamental knowledge to popularize the use of a helmet and the vehicle-fitted safety systems, and lay a strong foundation for the reconstruction of ESS-involved accidents. There is scope to improve safety for the use of ESS in public roads according to the analysis and conclusions. PMID- 26866284 TI - Investigating the Impact of Polymer Functional Groups on the Stability and Activity of Lysozyme-Polymer Conjugates. AB - Polymers are often conjugated to proteins to improve stability; however, the impact of polymer chain length and functional groups on protein structure and function is not well understood. Here we use RAFT polymerization to grow polymers of different lengths and functionality from a short acrylamide oligomer with a RAFT end group conjugated to lysozyme. We show by X-ray crystallography that enzyme structure is minimally impacted by modification with the RAFT end group. Significant activity toward the negatively charged Micrococcus lysodeicticus cell wall was maintained when lysozyme was modified with cationic polymers. Thermal and chemical stability of the conjugates was characterized using differential scanning fluorimetry and tryptophan fluorescence. All conjugates had a lower melting temperature; however, conjugates containing ionic or substrate mimicking polymers were more resistant to denaturation by guanidine hydrochloride. Our results demonstrate that tailoring polymer functionality can improve conjugate activity and minimize enzymatic inactivation by denaturants. PMID- 26866285 TI - Curriculum-based measurement of oral reading: A preliminary investigation of confidence interval overlap to detect reliable growth. AB - Curriculum-based measurement of oral reading (CBM-R) progress monitoring data is used to measure student response to instruction. Federal legislation permits educators to use CBM-R progress monitoring data as a basis for determining the presence of specific learning disabilities. However, decision making frameworks originally developed for CBM-R progress monitoring data were not intended for such high stakes assessments. Numerous documented issues with trend line estimation undermine the validity of using slope estimates to infer progress. One proposed recommendation is to use confidence interval overlap as a means of judging reliable growth. This project explored the degree to which confidence interval overlap was related to true growth magnitude using simulation methodology. True and observed CBM-R scores were generated across 7 durations of data collection (range 6-18 weeks), 3 levels of dataset quality or residual variance (5, 10, and 15 words read correct per minute) and 2 types of data collection schedules. Descriptive and inferential analyses were conducted to explore interactions between overlap status, progress monitoring scenarios, and true growth magnitude. A small but statistically significant interaction was observed between overlap status, duration, and dataset quality, b = -0.004, t(20992) =-7.96, p < .001. In general, confidence interval overlap does not appear to meaningfully account for variance in true growth across many progress monitoring conditions. Implications for research and practice are discussed. Limitations and directions for future research are addressed. (PsycINFO Database Record PMID- 26866283 TI - Resting-state low-frequency fluctuations reflect individual differences in spoken language learning. AB - A major challenge in language learning studies is to identify objective, pre training predictors of success. Variation in the low-frequency fluctuations (LFFs) of spontaneous brain activity measured by resting-state functional magnetic resonance imaging (RS-fMRI) has been found to reflect individual differences in cognitive measures. In the present study, we aimed to investigate the extent to which initial spontaneous brain activity is related to individual differences in spoken language learning. We acquired RS-fMRI data and subsequently trained participants on a sound-to-word learning paradigm in which they learned to use foreign pitch patterns (from Mandarin Chinese) to signal word meaning. We performed amplitude of spontaneous low-frequency fluctuation (ALFF) analysis, graph theory-based analysis, and independent component analysis (ICA) to identify functional components of the LFFs in the resting-state. First, we examined the ALFF as a regional measure and showed that regional ALFFs in the left superior temporal gyrus were positively correlated with learning performance, whereas ALFFs in the default mode network (DMN) regions were negatively correlated with learning performance. Furthermore, the graph theory based analysis indicated that the degree and local efficiency of the left superior temporal gyrus were positively correlated with learning performance. Finally, the default mode network and several task-positive resting-state networks (RSNs) were identified via the ICA. The "competition" (i.e., negative correlation) between the DMN and the dorsal attention network was negatively correlated with learning performance. Our results demonstrate that a) spontaneous brain activity can predict future language learning outcome without prior hypotheses (e.g., selection of regions of interest--ROIs) and b) both regional dynamics and network-level interactions in the resting brain can account for individual differences in future spoken language learning success. PMID- 26866286 TI - Excision Margins for Melanoma In Situ on the Head and Neck. AB - BACKGROUND: Complete surgical excision of melanoma in situ (MIS) is curative. A 5 mm margin is often taken as the standard primary excision margin despite increasing evidence that this is frequently inadequate for tumor clearance. OBJECTIVE: To calculate the proportion of patients requiring >5 mm margin for clearance and to investigate any patient/lesion characteristics necessitating larger margins. MATERIALS AND METHODS: Three hundred forty-three primary MIS cases on the head and neck treated in the authors' department by Mohs micrographic surgery (MMS) over a 65-month period were retrospectively analyzed. Records were made of patient and lesion characteristics, and the total surgical margin for clearance calculated. RESULTS: Sixty-five percent were cleared by a 5 mm margin; for a 97% clearance rate, 15 mm was necessary. The increased clearance with additional margin was significant (p < .0001). Patient age, lesion site, and preoperative size did not predict margin. CONCLUSION: These results verify that MIS on the head and neck can spread significantly beyond the clinical margin and demonstrate the importance of confirming clearance histologically before closure procedures. Mohs micrographic surgery has the advantage of total margin evaluation and where available it may be reasonable to start with a 5-mm margin. Where MMS is not a treatment option, the authors would advocate larger excision margins of >=10 mm. PMID- 26866287 TI - Conservative Treatment of Osteoradionecrosis of the Cranium After Treatment of Cutaneous Malignancy With Mohs Surgery and Postoperative Radiation. PMID- 26866288 TI - Surgical Treatment of Chronic Hidradenitis Suppurativa: CO2 Laser Stripping Second Intention Technique. PMID- 26866289 TI - The Treatment of Trigeminal Trophic Syndrome With a Thermoplastic Dressing. PMID- 26866291 TI - Integrated care for Down syndrome. AB - Down syndrome (DS), caused by an extra copy of chromosome 21 (trisomy 21), is the most intensively studied human aneuploidy condition. It is the leading cause of intellectual disability and birth defects. Although most prenatally diagnosed DS fetuses are aborted in Taiwan, there are still some infants with DS who are diagnosed after birth. In addition to intellectual disability, people with DS face systemic problems that include short stature, dysmorphism, congenital heart disease, congenital anomalies of gastrointestinal and genitourinary tracts, abnormal endocrine function, leukemia and leukemoid reactions. To provide better care for people with DS in Taiwan, we began the DS multi-disciplinary clinic that has opened once per month since November 2013. The multi-disciplinary clinic consists of several subspecialists who provide care for DS people. To date, approximately 200 patients have used the clinic. The average number of patients who use the clinic per month is 27+/-6 with a mean patient age of 16+/-12 years old (range 0.3-53 years). The average number of patients per specialist on each clinic day is 5.2+/-4.9 (range 0.5-20.9 patients). We focus on early detection and prevention of medical and developmental issues associated with DS. This coordinated approach allows DS patients and family to have more comprehensive care. PMID- 26866292 TI - Letter to the Editor. PMID- 26866290 TI - Junctional Adhesion Molecule-A Is Highly Expressed on Human Hematopoietic Repopulating Cells and Associates with the Key Hematopoietic Chemokine Receptor CXCR4. AB - Hematopoietic stem/progenitor cells (HSPCs) reside in specialized bone marrow microenvironmental niches, with vascular elements (endothelial/mesenchymal stromal cells) and CXCR4-CXCL12 interactions playing particularly important roles for HSPC entry, retention, and maintenance. The functional effects of CXCL12 are dependent on its local concentration and rely on complex HSPC-niche interactions. Two Junctional Adhesion Molecule family proteins, Junctional Adhesion Molecule-B (JAM)-B and JAM-C, are reported to mediate HSPC-stromal cell interactions, which in turn regulate CXCL12 production by mesenchymal stromal cells (MSCs). Here, we demonstrate that another JAM family member, JAM-A, is most highly expressed on human hematopoietic stem cells with in vivo repopulating activity (p < .01 for JAM-A(high) compared to JAM-A(Int or Low) cord blood CD34(+) cells). JAM-A blockade, silencing, and overexpression show that JAM-A contributes significantly (p < .05) to the adhesion of human HSPCs to IL-1beta activated human bone marrow sinusoidal endothelium. Further studies highlight a novel association of JAM-A with CXCR4, with these molecules moving to the leading edge of the cell upon presentation with CXCL12 (p < .05 compared to no CXCL12). Therefore, we hypothesize that JAM family members differentially regulate CXCR4 function and CXCL12 secretion in the bone marrow niche. Stem Cells 2016;34:1664-1678. PMID- 26866293 TI - Generalizability of Patients With Rheumatoid Arthritis in Biologic Agent Clinical Trials. AB - OBJECTIVE: Randomized controlled trials (RCTs) have consistently demonstrated the efficacy of biologic agents in treating patients with rheumatoid arthritis (RA) who satisfy strict eligibility criteria, yet studies report that a majority of RA patients in the US have had biologic treatment exposure. We identified the proportion of RA patients in clinical practice satisfying entry criteria for biologic agent RCTs. METHODS: Eligibility criteria of 30 RCTs of 10 Food and Drug Administration-approved biologic agents to treat RA were reviewed, summarized, and applied to 2 observational clinical cohorts: the Veterans Affairs Rheumatoid Arthritis registry (VARA; n = 1,523) and the Rheumatology and Arthritis Investigational Network Database (RAIN-DB; n = 1,548). Patients at a single clinical encounter were assessed for overall trial eligibility as well as eligibility across 3 domains: demographics, disease activity, and medication exposure. RESULTS: The mean percentage of patients that satisfied eligibility criteria was 3.7% (interquartile range [IQR] 1.5-3.1) in VARA and 7.1% (IQR 4.4 7.7) in RAIN-DB. Ineligibility was most often due to low disease activity, specifically low joint counts. The mean Disease Activity Score in 28 joints at enrollment was 6.59 (range 6.1-7.1) across RCTs versus 3.87 (0.07-8.69) in VARA and 3.65 (0.49-7.21) in RAIN-DB. RCTs for non-tumor necrosis factor (TNF) inhibitor biologic agents were more restrictive than RCTs for TNF inhibitors. There was no trend in eligibility by RCT study publication or drug approval date. CONCLUSION: The vast majority of RA patients from our clinical cohorts did not satisfy criteria for participation in biologic agent RCTs. These findings underscore the need for caution in extrapolating trial results to day-to-day management of RA patients and may provide insight into the differential responses to biologic agents reported in prior observational studies. PMID- 26866294 TI - Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure. AB - Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (lambdamax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation. Our results show that photosensitized RB generates (1)O2 via Type-II photodynamic pathway and induced DNA damage under sunlight/UV-R exposure. 2'dGuO degradation, micronuclei formation, and single- and double-strand breakage were the outcome of photogenotoxicity caused by RB. Quenching studies with NaN3 advocate the involvement of (1)O2 in RB photogenotoxicity. RB induced linoleic acid photoperoxidation, which was parallel to (1)O2-mediated DNA damage. Oxidative stress in A375 cell line (human melanoma cell line) was detected through DCF-DA assay. Photosensitized RB decreased maximum cellular viability under sunlight followed by UV-B and UV-A exposures. Apoptosis was detected as a pattern of cell death through the increased of caspase-3 activity, decreased mitochondrial membrane potential, and PS translocation through inner to outer plasma membrane. Increased cytosolic levels of Bax also advocate the apoptotic cell death. We propose a p53-mediated apoptosis via increased expression of Bax gene and protein. Thus, the exact mechanism behind RB phototoxicity was the involvement of (1)O2, which induced oxidative stress-mediated DNA and membrane damage, finally apoptotic cell death under natural sunlight exposure. The study suggests that after the use of RB, sunlight exposure may avoid to prevent from its harmful effects. PMID- 26866295 TI - A Longitudinal Study to Evaluate Pregnancy-Induced Endogenous Analgesia and Pain Modulation. AB - BACKGROUND AND OBJECTIVES: The phenomenon of pregnancy-induced analgesia has been demonstrated in animal models but less consistently in human studies. This study aimed to assess endogenous pain modulation, evaluating inhibitory and excitatory pain pathways, over the course of pregnancy and postpartum. METHODS: Healthy pregnant women were approached for participation in this prospective multicenter cohort study. Conditioned pain modulation (CPM), mechanical temporal summation (mTS), and temperature that induced pain 6 out of 10 (pain-6) were assessed toward the end of each trimester of pregnancy (8-12, 18-22, and 36 weeks) and at 6 to 12 weeks postpartum. To assess how pregnancy affects CPM, mTS, and pain-6, a mixed-effects analysis of variance was performed. RESULTS: Thirty-three pregnant women were enrolled. Pregnancy did not significantly impact CPM (F3,39 = 0.30, P = 0.83, partial eta = 0.02), and there was no significant difference between CPM scores in the third trimester compared with postpartum. The mTS scores and pain-6 ratings were also not significantly changed by pregnancy (F3,42 = 1.20, P = 0.32, partial eta = 0.08; and F3,42 = 1.90, P = 0.14, partial eta = 0.12, respectively). CONCLUSIONS: This is the first study to assess CPM and mTS changes in pregnancy and postpartum. Endogenous pain modulation evaluating both inhibitory and excitatory pain pathways did not significantly change during pregnancy or postpartum. Future studies are required to determine the magnitude and clinical significance of pregnancy-induced analgesia. PMID- 26866296 TI - Comparative-Effectiveness of Simulation-Based Deliberate Practice Versus Self Guided Practice on Resident Anesthesiologists' Acquisition of Ultrasound-Guided Regional Anesthesia Skills. AB - BACKGROUND AND OBJECTIVES: Simulation-based education strategies to teach regional anesthesia have been described, but their efficacy largely has been assumed. We designed this study to determine whether residents trained using the simulation-based strategy of deliberate practice show greater improvement of ultrasound-guided regional anesthesia (UGRA) skills than residents trained using self-guided practice in simulation. METHODS: Anesthesiology residents new to UGRA were randomized to participate in either simulation-based deliberate practice (intervention) or self-guided practice (control). Participants were recorded and assessed while performing simulated peripheral nerve blocks at baseline, immediately after the experimental condition, and 3 months after enrollment. Subject performance was scored from video by 2 blinded reviewers using a composite tool. The amount of time each participant spent in deliberate or self guided practice was recorded. RESULTS: Twenty-eight participants completed the study. Both groups showed within-group improvement from baseline scores immediately after the curriculum and 3 months following study enrollment. There was no difference between groups in changed composite scores immediately after the curriculum (P = 0.461) and 3 months following study enrollment (P = 0.927) from baseline. The average time in minutes that subjects spent in simulation practice was 6.8 minutes for the control group compared with 48.5 minutes for the intervention group (P < 0.001). CONCLUSIONS: In this comparative effectiveness study, there was no difference in acquisition and retention of skills in UGRA for novice residents taught by either simulation-based deliberate practice or self guided practice. Both methods increased skill from baseline; however, self-guided practice required less time and faculty resources. PMID- 26866297 TI - Real-Time Detection of Periforaminal Vessels in the Cervical Spine: An Ultrasound Survey. AB - BACKGROUND AND OBJECTIVES: Compared with the thoracic and lumbar spine, transforaminal epidural injections and medial branch blocks in the cervical spine are associated with a higher incidence of neurological complications. Accidental breach of small periforaminal arteries has been implicated in many instances. In this observational study, using ultrasonography, we surveyed the incidence of periforaminal bloods vessels in the cervical spine. METHODS: Patients undergoing ultrasound-guided cervical medial branch blocks were scanned using color power and pulsed wave Doppler. Five levels from C2/C3 to C6/C7 were studied. Incidental blood vessels located between the anterior tubercles of the transverses process and the posterior borders of the articular pillars were included for analysis. We recorded the diameter and position of arteries relative to contiguous bony landmarks as well the number of veins. RESULTS: In 102 patients, we performed a total 201 scans (1005 cervical levels). Of the 363 incidental vessels identified, 238 were arteries (mean diameter, 1.25 +/- 0.45 mm). The latter were most commonly found at the posterior foraminal aspects of C5, C6, and C7 (13%, 11%, and 16% of scans, respectively); the transverse processes of C5 and C6 (10% and 16% of scans, respectively); and the articular pillars of C6 and C7 (19% and 16% of scans, respectively). CONCLUSIONS: Small periforaminal arteries are prevalent along the lateral aspect of the cervical spine, adjacent to areas commonly targeted by nerve block procedures. Further trials are required to determine if ultrasound guidance can reduce the incidence of complications related to accidental vascular breach. PMID- 26866298 TI - Sudden Intrathecal Drug Delivery Device Motor Stalls: A Case Series. AB - BACKGROUND AND OBJECTIVES: Intrathecal (IT) drug delivery systems (IDDSs) have been valuable in managing refractory chronic cancer and noncancer pain for more than 3 decades. These devices, time tested and overall reliable, have lately been noted at this institution to cease infusing unexpectedly. If not immediately recognized and rectified, this abrupt malfunction may lead to significant patient harm. METHODS: A series of 13 patients from 1 academic center whose Medtronic SynchroMed II pumps malfunctioned from 2013 to 2015 is described. Data from the patient population with regard to variables that may increase the rate of IDDS malfunction are analyzed. The risk factors for IDDS malfunction, Medtronic-issued recalls, and current literature on IT device failure are reviewed. RESULTS: The total prevalence of device motor stall among the population of this institution is 9.03%. The incidence rate of IDDS failure is calculated at 0.04 device failures per patient per year. Increased length of time from implant was the only statistically significant (P = 0.00009) risk factor for device failure identified in this population. Dysfunction in the motor gear train was found after destructive analysis of several devices in this series. CONCLUSIONS: Higher rates of device failure are associated with the use of off-label IT drugs. However, device failure may still occur while infusing only approved medications. Implanted patients should be properly informed and educated to differentiate and recognize the critical error alarm of their device as well as the signs and symptoms of IT medication overdose and withdrawal. PMID- 26866299 TI - Update on Ultrasound for Truncal Blocks: A Review of the Evidence. AB - We summarized the evidence for ultrasound (US) guidance for truncal blocks in 2010 by performing a systematic literature review and rating the strength of evidence for each block using a system developed by the United States Agency for Health Care Policy and Research. Since then, numerous studies of US guidance for truncal blocks have been published. In addition, 3 novel US-guided blocks have been described since our last review. To provide updated recommendations, we performed another systematic search of the literature to identify studies pertaining to US guidance for the following blocks: paravertebral, intercostal, transversus abdominis plane, rectus sheath, ilioinguinal/iliohypogastric, as well as the Pecs, quadratus lumborum, and transversalis fascia blocks. We rated the methodologic quality of each of the identified studies and then graded the strength of evidence supporting the use of US for each block based on the number and quality of available studies for that block. WHAT'S NEW: Since our last review, numerous studies have been published, especially for the paravertebral and transversus abdominis plane blocks, and 3 novel US-guided blocks (Pecs, quadratus lumborum, and transversalis fascia blocks) have been described. Although some of these studies support the use of US for performing these blocks, others do not. Additional studies have used US to improve our understanding of the anatomy pertinent to these blocks and evaluated the effect on patient outcomes and risk of complications. PMID- 26866300 TI - Liposomal adjuvants for human vaccines. AB - INTRODUCTION: Liposomes are well-known as drug carriers, and are now critical components of two of six types of adjuvants present in licensed vaccines. The liposomal vaccine adjuvant field has long been dynamic and innovative, and research in this area is further examined as new commercial products appear in parallel with new vaccines. In an arena where successful products exist the potential for new types of vaccines with liposomal adjuvants, and alternative liposomal adjuvants that could emerge for new types of vaccines, are discussed. AREAS COVERED: Major areas include: virosomes, constructed from phospholipids and proteins from influenza virus particles; liposomes containing natural and synthetic neutral or anionic phospholipids, cholesterol, natural or synthetic monophosphoryl lipid A, and QS21 saponin; non-phospholipid cationic liposomes; and combinations and mixtures of liposomes and immunostimulating ingredients as adjuvants for experimental vaccines. EXPERT OPINION: Liposomes containing monophosphoryl lipid A and QS21 have considerable momentum that will result soon in emergence of prophylactic vaccines to malaria and shingles, and possible novel cancer vaccines. The licensed virosome vaccines to influenza and hepatitis A will be replaced with virosome vaccines to other infectious diseases. Alternative liposomal formulations are likely to emerge for difficult diseases such as tuberculosis or HIV-1 infection. PMID- 26866301 TI - Complex chromosomal rearrangement involving five chromosomes: deciphering genomic imbalances in an apparently balanced chromosomal translocation. PMID- 26866302 TI - A bright and colorful future for DNA cell cycle analysis. PMID- 26866303 TI - Determination of Concentration of Amphiphilic Polymer Molecules on the Surface of Encapsulated Semiconductor Nanocrystals. AB - We present a method for the determination of the average number of polymer molecules on the surface of A(II)B(VI) luminescent core-shell nanocrystals (CdSe/ZnS, ZnSe/ZnS quantum dots, and CdS/ZnS nanorods) encapsulated with amphiphilic polymer. Poly(maleic anhydride-alt-1-tetradecene) (PMAT) was quantitatively labeled with amino-derivative of fluorescein and the average amount of PMAT molecules per single nanocrystal was determined using optical absorption of the dye in the visible spectral range. The average amount of PMAT molecules grows linearly with the surface area of all studied nanocrystals. However, the surface density of the monomer units increases nonlinearly with the surface area, because of the increased competition between PMAT molecules for Zn hexanethiol surface binding sites. The average value of zeta potential (zeta = 35 mV) was found to be independent of the size, shape, and chemical composition of nanocrystals at fixed buffer parameters (carbonate-bicarbonate buffer, pH 9.5 and 5 mM ionic strength). This finding is expected to be useful for the determination of the surface density of remaining carboxyl groups in PMAT encapsulated nanocrystals. PMID- 26866304 TI - Diagnosis of placental abruption: a legal issue for physicians. PMID- 26866305 TI - Association Between Human Hair Loss and the Expression Levels of Nucleolin, Nucleophosmin, and UBTF Genes. AB - AIMS: Nucleolar organizer regions, also known as argyrophilic nucleolar organizer regions, are associated with ribosomal genes. The main function of the nucleolus is the rapid production of ribosomal subunits, a process that must be highly regulated to provide the appropriate levels for cellular proliferation and cell growth. There are no studies in the literature addressing the expression and function of nucleolar component proteins, including nucleophosmin, nucleolin and the upstream binding transcription factor (UBTF), in human follicular hair cells. METHODS: Nineteen healthy males who had normal and sufficient hair follicles on the back of the head, but exhibited hair loss on the frontal/vertex portions of the head and 14 healthy males without hair loss were included in the current study. Gene expression levels were measured by relative quantitative real time polymerase chain reaction. RESULTS: In the individuals suffering from alopecia, the total expression levels of nucleolin, nucleophosmin, and UBTF were lower in normal sites than in hair loss sites. Strong expression level correlations were detected between: nucleophosmin and nucleolin; nucleophosmin and UBTF, and nucleolin and UBTF for both groups. CONCLUSIONS: There was an association between human hair loss and the expression levels of nucleolin, nucleophosmin, and UBTF genes. PMID- 26866306 TI - Effects of transcytolemmal water exchange on the assessment of myocardial extracellular volume with cardiovascular MRI. AB - Quantitative analysis of the myocardial interstitial space is gaining increased interest as a biomarker in the MRI and clinical cardiovascular communities. To investigate the effect of water exchange on the calculation of myocardial extracellular volume (ECV), we employed two tissue models: the standard ECV two point model (SM) and the shutter speed model (SSM). Twenty individuals (18 men and two women; age 61.9 +/- 10.3 years) underwent MRI at 1.5 T with pre-contrast and post-contrast dynamic T1 quantification. Means, standard deviations and ranges for SM and SSM model parameters were calculated. Infarct and viable myocardial model parameters as well as apparent ECV values calculated with the SM and SSM were statistically compared. Viable ECV(SM) remained temporally constant (27.3-28.0%: P = 0.5) and infarcted myocardial ECV(SM) changed significantly (49.3-58.8%; P < 0.001), reaching a steady-state value after 15 min. The intracellular lifetime of water was three times greater in infarcted myocardium when compared with viable myocardium (taui: 66.6 +/- 115 versus 208.7 +/- 72.7 ms) and accompanied a twofold increase in ECV (ECV(SSM) : 30.3 +/- 11.1 versus 71.0 +/- 13.1%; P < 0.001). There was a consistent significant difference in ECV values of infarcted myocardium at different timepoints between the SM and SSM, but not viable myocardium, presumably due to slower water exchange. In summary, we found a significant change in apparent ECV and water exchange in infarcted myocardium when compared with viable myocardium. This was visualized by changes in dynamic contrast enhanced curve shapes and quantified using the SSM as not only an increase in apparent ECV but also a decrease in water exchange. PMID- 26866307 TI - Mass Spectrometry Uncovers Molecular Reactivities of Coordination and Organometallic Gold(III) Drug Candidates in Competitive Experiments That Correlate with Their Biological Effects. AB - The reactivity of three cytotoxic organometallic gold(III) complexes with cyclometalated C,N,N and C,N ligands (either six- or five-membered metallacycles), as well as that of two representative gold(III) complexes with N donor ligands, with biological nucleophiles has been studied by ESI-MS on ion trap and time-of-flight instruments. Specifically, the gold compounds were reacted with mixtures of nucleophiles containing l-histidine (imine), l methionine (thioether), l-cysteine (thiol), l-glutamic acid (carboxylic acid), methylseleno-l-cysteine (selenoether), and in situ generated seleno-l-cysteine (selenol) to judge the preference of the gold compounds for binding to selenium containing amino acid residues. Moreover, the gold compounds' reactivity was studied with proteins and nucleic acid building blocks. These experiments revealed profound differences between the coordination and organometallic families and even within the family of organometallics, which allowed insights to be gained into the compounds mechanisms of action. In particular, interactions with seleno-l-cysteine appear to reflect well the compounds' inhibition properties of the seleno-enzyme thioredoxin reductase and to a certain extent their antiproliferative effects in vitro. Therefore, mass spectrometry is successfully applied for linking the molecular reactivity and target preferences of metal-based drug candidates to their biological effects. Finally, this experimental setup is applicable to any other metallodrug that undergoes ligand substitution reactions and/or redox changes as part of its mechanism of action. PMID- 26866308 TI - Expanding metabolite coverage of real-time breath analysis by coupling a universal secondary electrospray ionization source and high resolution mass spectrometry--a pilot study on tobacco smokers. AB - Online breath analysis is an attractive approach to track exhaled compounds without sample preparation. Current commercially available real-time breath analysis platforms require the purchase of a full mass spectrometer. Here we present an ion source compatible with virtually any preexisting atmospheric pressure ionization mass spectrometer that allows real-time analysis of breath. We illustrate the capabilities of such technological development by upgrading an orbitrap mass spectrometer. As a result, we detected compounds in exhaled breath between 70 and 900 Da, with a mass accuracy of typically <1 ppm; resolutions between m/Deltam 22,000 and 70,000 and fragmentation capabilities. The setup was tested in a pilot study, comparing the breath of smokers (n = 9) and non smokers (n = 10). Exogenous compounds associated to smoking, as well as endogenous metabolites suggesting increased oxidative stress in smokers, were detected and in some cases identified unambiguously. Most of these compounds correlated significantly with smoking frequency and allowed accurate discrimination of smokers and non-smokers. PMID- 26866309 TI - Iodine-Mediated Intramolecular Dehydrogenative Coupling: Synthesis of N Alkylindolo[3,2-c]- and -[2,3-c]quinoline Iodides. AB - An I2/TBHP-mediated intramolecular dehydrogenative coupling reaction is developed for the synthesis of a library of medicinally important 5,11-dialkylindolo[3,2 c]quinoline salts and 5,7-dimethylindolo[2,3-c]quinoline salts. The annulation reaction is followed by aromatization to yield tetracycles in good yield. This protocol is also demonstrated for the synthesis of the naturally occurring isocryptolepine in salt form. PMID- 26866310 TI - The Use of Low-Dose Oral Glucocorticoids Was Minimized in the 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: Comment on the Article by Singh et al. PMID- 26866311 TI - Transitions. PMID- 26866312 TI - Lateral Ulnar Collateral Ligament Reconstruction: An Analysis of Ulnar Tunnel Locations. AB - We conducted a study to determine precise ulnar tunnel location during lateral ulnar collateral ligament reconstruction to maximize bony bridge and graft construct perpendicularity. Three-dimensional computer models of 15 adult elbows were constructed. These elbow models were manipulated for simulated 4-mm tunnel drilling. The proximal ulna tunnels were placed at the radial head-neck junction and sequentially 0, 5, and 10 mm posterior to the supinator crest. The bony bridges created by these tunnels were measured. Location of the humeral isometric point was determined and marked as the humeral tunnel location. Graft configuration was simulated. Using all the simulated ulna tunnels, we measured the proximal and distal limbs of the graft. In addition, we measured the degree of perpendicularity of the graft limbs. The ulnar tunnel bony bridge was significantly longer with more posterior placement of the proximal tunnel relative to the supinator crest. An increase in degree of perpendicularity of graft to ulnar tunnels was noted with posterior shifts in proximal tunnel location. Posterior placement of the proximal ulna tunnel allows for a larger bony bridge and a more geometrically favorable reconstruction. PMID- 26866313 TI - Navigating the Alphabet Soup of Labroligamentous Pathology of the Shoulder. AB - Because of the widespread use of eponyms and acronyms to describe labroligamentous findings in the shoulder, interpreting shoulder magnetic resonance imaging reports can be challenging. A summary of the appearance of these lesions on shoulder magnetic resonance images can help the orthopedic surgeon to understand these entities as imaging findings and to determine the appropriate treatment for patients with shoulder injuries. PMID- 26866314 TI - Minimum 5-Year Results With Duracon Press-Fit Metal-Backed Patellae. AB - Negative outcomes of earlier metal-backed patella designs have overshadowed reports of positive outcomes achieved with careful attention paid to component design, patellar tracking, and surgical technique. Much as reported elsewhere, we found earlier component failures were caused by poor locking mechanisms, thin polyethylene, poor tracking, and minimal femur contact. Over the past decade, however, our outcomes with Duracon metal-backed patellae have been encouraging. We think these positive outcomes, seen over a minimum 5-year follow-up, are largely attributable to the thicker polyethylene and improved articular conformity of this component relative to earlier designs. PMID- 26866315 TI - Nonoperative Treatment of Rotator Cuff Tears. PMID- 26866316 TI - Subpectoral Biceps Tenodesis. AB - Biceps tenodesis is a common procedure performed for tendinopathy of the long head of the biceps brachii (LHB). Indications include partial-thickness LHB tear, tendon subluxation with or without subscapularis tear, and failed conservative management of bicipital tenosynovitis. Biceps tenodesis may also be performed for superior labrum anterior to posterior tears. Evaluation of biceps stability is important in the treatment of LHB pathology. We advocate a technique of subpectoral biceps tenodesis. Interference screw fixation has demonstrated biomechanical superiority in laboratory models. If there are any concomitant operations, such as rotator cuff repair, the postoperative rehabilitation protocol may need to be adjusted. Overall, subpectoral biceps tenodesis with interference screw fixation has had excellent clinical outcomes and low complication rates. PMID- 26866317 TI - Implant Designs in Revision Total Knee Arthroplasty. PMID- 26866318 TI - Outcomes and Aseptic Survivorship of Revision Total Knee Arthroplasty. PMID- 26866319 TI - Distal Ulna Fracture With Delayed Ulnar Nerve Palsy in a Baseball Player. AB - We present a case report of a college baseball player who sustained a blunt trauma, distal-third ulna fracture from a thrown ball with delayed presentation of ulnar nerve palsy. Even after his ulna fracture had healed, the nerve injury made it difficult for the athlete to control a baseball while throwing, resulting in a delayed return to full baseball activity for 3 to 4 months. He had almost complete nerve recovery by 6 months after his injury and complete nerve recovery by 1 year after his injury. PMID- 26866320 TI - Adipose Flap Versus Fascial Sling for Anterior Subcutaneous Transposition of the Ulnar Nerve. AB - Perineural scarring is a major cause of recurrent symptoms after anterior subcutaneous transposition secured with a fascial sling. Use of a vascularized adipose flap to secure the anteriorly transposed ulnar nerve can help reduce nerve adherence and may enhance nerve recovery. In the study reported here, we retrospectively reviewed the long-term outcomes of ulnar nerve anterior subcutaneous transposition secured with either an adipose flap (16 patients) or a fascial sling (17 patients). The 33 patients underwent physical examinations and completed the DASH (Disabilities of the Arm, Shoulder, and Hand) questionnaire, visual analog scales (VASs), and the Modified Bishop Rating Scale (MBRS). There were no significant differences in DASH (P = .673), VAS pain (P = .413), or VAS weakness (P = .362) scores between the adipose flap and fascial sling groups. Physical examinations revealed no significant differences in flexion-extension arc (P = .668) or supination-pronation arc (P = .226) between the operated and nonoperated extremities. Lateral pinch strength and grip strength were comparable. On the MBRS, excellent and good outcomes were reported by 62.5% and 37.5% of the adipose flap patients, respectively, and 59% and 41% of the fascial sling patients. The contribution of perineural scarring to postoperative recurrent ulnar neuropathy is well documented. We think the pedicled adipofascial flap benefits the peripheral nerve by providing a scar tissue barrier and an optimal milieu for vascular regeneration. For all patients in the present study, symptoms improved, though the adipose flap and fascial sling groups were not significantly different in their objective outcomes. Subjective results were slightly better for the adipose flap patients but not significantly so. These findings indicate that, compared with the current standard of care, adipose flaps are more efficacious in securing the anteriorly transposed nerve. PMID- 26866321 TI - Improving Spanning-Knee External Fixator Stiffness: A Biomechanical Study. AB - The purpose of this study was to test and compare external fixator construct stiffness using pin-to-bar clamps or multipin clamps across 2 external fixation systems. Constructs were tested with 8-mm and 11-mm-diameter bar systems and pin to-bar or multipin clamps. Three construct designs were tested: construct 1 with a single crossbar and pin-to-bar clamps, construct 2 with 2 crossbars and pin-to bar clamps, and construct 3 with 2 crossbars and multipin clamps. The stiffness of each construct (N = 24) was tested using anterior-posterior bending. Two crossbars and pin-to-bar clamps resulted in the highest mean stiffness. Constructs with a single crossbar and pin-to-bar clamps had a similar average stiffness compared with constructs with 2 crossbars and multipin clamps. Pin-to bar clamps with 2 crossbars result in stronger spanning-knee external fixators than constructs using multipin clamps. PMID- 26866322 TI - Novel Intraoperative Technique to Visualize the Lower Cervical Spine: A Case Series. AB - Visualization of the lower cervical spine with a lateral radiograph poses a challenge secondary to encroachment of the shoulders. Applying traction to the arms or taping the shoulders down provides adequate visualization in most patients, but imaging the mid- to lower cervical levels presents a significant challenge in patients with stout necks. We present a variation of the lateral radiograph that is 30o oblique from horizontal and 30o cephalad from neutral and used in a series of patients with stout necks that require anterior instrumentation of the lower cervical spine. We reviewed intraoperative images of 2 patients who underwent anterior cervical spine surgery at our institution, and assessed type of procedure, body mass index, and outcome scores. Our variation provided improved visualization relative to a lateral view and was used intraoperatively to confirm correct-level hardware placement in both patients. PMID- 26866323 TI - Ureter and Nerve Root Compression Secondary to Expansile Fibrous Dysplasia of the Transverse Process. AB - Considering their proximity to abdominal viscera, transverse process lesions may pose a diagnostic challenge. We present a case of fibrous dysplasia of the transverse process, causing urinary retention, frequent urinary tract infections, and thigh numbness. This is the first reported case of a transverse process fibrous dysplasia lesion, causing simultaneous urinary retention and neurologic symptoms. Clinicians may consider lesions of the lumbar transverse processes in patients presenting to orthopedic surgeons with urinary symptoms, especially when combined with neurologic symptoms. In these lesions, fibrous dysplasia should be within the differential diagnosis. We discuss the diagnosis and present a brief review of fibrous dysplasia. PMID- 26866324 TI - Differences in Innovative Behavior Among Hospital-Based Registered Nurses. AB - BACKGROUND: The 2010 Institute of Medicine report, 'The Future of Nursing: Leading Change, Advancing Health', advocated for nurses to innovate in their practice, research, and education. However, little is known about the innovative behavior of registered nurses or whether there are differences in innovative behavior among registered nurses. OBJECTIVE: The purpose of this article is to describe the innovative behavior of hospital-based registered nurses and understand the differences in innovative behavior when registered nurses are categorized into various demographic groups. METHODS: A survey of 251 hospital based registered nurses from 9 hospitals in California was administered to assess demographic characteristics and innovative behavior, measured through Scott and Bruce's Individual Innovative Behavior Scale. RESULTS: Hospital-based registered nurses, on average, reported moderate levels of innovative behavior. There were statistically significant differences in innovative behavior when registered nurses were categorized according to specialty certification, role, level of education, hospital size, and hospital innovativeness. CONCLUSIONS: To support innovative behavior, organizations should provide opportunities for specialty certification and increasing levels of education. PMID- 26866325 TI - Measuring Nurse Caring Behaviors in the Hospitalized Older Adult. AB - OBJECTIVE: The aim of this study was to investigate the relationship between nurse caring behavior scores and the use of the "Get to Know Me" poster in hospitalized older adults. BACKGROUND: Hospitalization can be an isolating experience for the patient and his/her family. Within the high-tech healthcare arena, the focus of the "patient/person" can be lost. The art of caring and basic communication between the nurse and person is essential to nursing. METHODS: This was a 2-group quasi-experimental pretest-posttest design using the intervention of the Get to Know Me poster and measurement of nurse caring behaviors with the Caring Assessment of Care Givers (CACG) instrument. RESULTS: Nurse caring behavior scores of the nurses in the experimental group who utilized the Get to Know Me poster were significantly higher on the total CACG scores as well on the subscale dimensions of maintaining belief, being with, and doing for than those of the nurses forming the control group. CONCLUSIONS: The results of this research indicated that interventions that focus the attention on the person and emphasize patient-focused care can enhance nurse caring behaviors and strengthen the patient-nurse relationship. PMID- 26866327 TI - Does prism adaptation affect visual search in spatial neglect patients: A systematic review. AB - Prism adaptation (PA) is a widely used intervention for (visuo-)spatial neglect. PA-induced improvements can be assessed by visual search tasks. It remains unclear which outcome measures are the most sensitive for the effects of PA in neglect. In this review, we aimed to evaluate PA effects on visual search measures. A systematic literature search was completed regarding PA intervention studies focusing on patients with neglect using visual search tasks. Information about study content and effectiveness was extracted. Out of 403 identified studies, 30 met the inclusion criteria. The quality of the studies was evaluated: Rankings were moderate-to-high for 7, and low for 23 studies. As feature search was only performed by five studies, low-to-moderate ranking, we were limited in drawing firm conclusions about the PA effect on feature search. All moderate-to high-ranking studies investigated cancellation by measuring only omissions or hits. These studies found an overall improvement after PA. Measuring perseverations and total task duration provides more specific information about visual search. The two (low ranking) studies that measured this found an improvement after PA on perseverations and duration (while accuracy improved for one study and remained the same for the other). This review suggests there is an overall effect of PA on visual search, although complex visual search tasks and specific visual search measures are lacking. Suggestions for search measures that give insight in subcomponents of visual search are provided for future studies, such as perseverations, search path intersections, search consistency and using a speed-accuracy trade-off. PMID- 26866326 TI - Does an Insulin Double-Checking Procedure Improve Patient Safety? AB - OBJECTIVE: The aim of this study was to examine the effectiveness of a subcutaneous insulin double-checking preparation intervention on insulin administration errors. BACKGROUND: Insulin accounts for 3.5% of medication related errors. The Joint Commission and Institute for Safe Medication Practices recommend a 2-nurse double-checking procedure when preparing insulin. METHODS: This study used a randomized, controlled, nonblinded, intent-to-treat methodology. RESULTS: In total, 266 patients were enrolled, and over 4 weeks of data collection, there were 5238 opportunities for insulin administration. Overall, 3151 insulin administration opportunities had no errors; the double checking group had more no-error periods than usual care. Of error types, wrong time was predominant, but less prevalent in the double-checking group. Omission errors were uncommon and occurred less in the double-checking group. CONCLUSIONS: The subcutaneous insulin double-checking preparation procedure led to less insulin administration errors; however, timing errors were most prevalent and are not resolved with double-checking interventions. PMID- 26866329 TI - Infrabrow Skin Excision Associated With Upper Blepharoplasty to Address Significant Dermatochalasis With Lateral Hooding in Select Asian Patients. AB - PURPOSE: In Asian patients, lateral hooding in the aging upper eyelid is prominent and frequently seen. Removal of the redundant skin of this region during classic blepharoplasty tends to produce a resultant prolonged scar. Furthermore, as the height of the eyelid skin excision increases, suturing of the thick upper skin to the thin pretarsal skin can result in upper lid fullness. This study documents the combination of infrabrow skin excision and upper blepharoplasty to address lateral hooding in select patients of Asian ancestry. METHODS: This study is a retrospective chart review of patients who underwent infrabrow skin excision associated with upper blepharoplasty. The inclusion criteria were moderate and severe upper eyelid dermatochalasis in patients with high eyebrows and lateral hooding; residual lateral hooding following previous blepharoplasty. RESULTS: Thirty-two eyelids of 16 female patients of Japanese ancestry underwent infrabrow skin excision associated with upper blepharoplasty. The mean age of patients was 68.87 +/- 7.88 years (57-82 years). Mean follow up was 37.25 +/- 18.96 months (9-72 months). Patients were evaluated at 1, 3, 6, and 9 months at least. The Strasser system for evaluation of surgical results was applied at 3 months. All patients had scores indicating good results and were satisfied with the cosmetic outcome and improvement of visual field after surgery. No complications related to wound dehiscence, lagophthalmos, hypertrophic scars, or sensory changes were observed. CONCLUSION: The combination of infrabrow skin excision and upper blepharoplasty was effective to address moderate and severe dermatochalasis with lateral hooding in select patients of Japanese ancestry. PMID- 26866328 TI - Recent advances in globin research using genome-wide association studies and gene editing. AB - A long-sought goal in the hemoglobin field has been an improved understanding of the mechanisms that regulate the switch from fetal (HbF) to adult (HbA) hemoglobin during development. With such knowledge, the hope is that strategies for directed reactivation of HbF in adults could be devised as an approach to therapy for the beta-hemoglobinopathies thalassemia and sickle cell disease. Recent genome-wide association studies (GWAS) led to identification of three loci (BCL11A, HBS1L-MYB, and the beta-globin cluster itself) in which natural genetic variation is correlated with different HbF levels in populations. Here, the central role of BCL11A in control of HbF is reviewed from the perspective of how findings may be translated to gene therapy in the not-too-distant future. This summary traces the evolution of recent studies from the initial recognition of BCL11A through GWAS to identification of critical sequences in an enhancer required for its erythroid-specific expression, thereby highlighting an Achilles heel for genome editing. PMID- 26866330 TI - Comparison of Two Polypropylene Frontalis Suspension Techniques in 92 Patients With Oculopharyngeal Muscular Dystrophy. AB - PURPOSE: To compare the functional outcome of the polypropylene trapezoid frontalis suspension with the polypropylene modified Crawford frontalis suspension in a large cohort of patients with oculopharyngeal muscular dystrophy. METHODS: Retrospective, nonrandomized comparative case series. Patients with oculopharyngeal muscular dystrophy who underwent bilateral polypropylene frontalis suspension were selected for chart review. Main outcome measures were margin reflex distance, duration of surgery, and ptosis recurrence. RESULTS: Ninety-two patients qualified for chart review; 39 patients underwent the trapezoid sling and 53 patients the modified Crawford sling. There was no difference in preoperative margin reflex distance or levator function between the 2 surgical groups. Postoperative improvement in margin reflex distance was 2.95 +/- 1.56 mm in the trapezoid group compared with 2.85 +/- 1.65 mm in the modified Crawford group (p = 0.67). Duration of surgery was 40.49 +/- 13.33 minutes in the trapezoid group compared with 53.77 +/- 16.04 minutes in the modified Crawford group (p < 0.001). Five percent of eyes in the trapezoid group had ptosis recurrence compared with 13% of eyes in the modified Crawford group (p = 0.07). CONCLUSION: Both polypropylene frontalis suspension techniques generated an equivalent increase in margin reflex distance. However, the trapezoid frontalis suspension required less operative time and trended toward a lower rate of ptosis recurrence. PMID- 26866331 TI - IgG4-Related Disease of the Punctum and Canaliculus. AB - A 60-year-old man with no past medical history presented with a 14-month history of a painless medial left lower eyelid mass causing mechanical ectropion and discharge from the inferior punctum. Excisional biopsy was performed via a transconjunctival canaliculotomy and histopathology revealed a dense plasma cell infiltrate with IgG4+ plasma cells >100/high power field and an IgG4/IgG ratio of 65%. Serum IgG4 was found to be elevated at 224 mg/dl (reference range: 4-86 mg/dl). Systemic work up with PET CT was negative. The patient's signs and symptoms all resolved without medical treatment and he remains disease free 24 months following surgery. A single case of IgG4 disease of the nasolacrimal duct has been reported, but to the authors' knowledge, disease involving the proximal nasolacrimal outflow system has yet to be described. The authors herein report a case of IgG4-related disease involving the punctum and canaliculus. PMID- 26866332 TI - Orbital Volume Augmentation for Enophthalmos Following Ventriculoperitoneal Shunting: A Case Study in "Silent Brain Syndrome". AB - A 21-year-old female with a history of infantile hydrocephalus and ventriculoperitoneal shunting presented with bilateral persistent tearing. Examination revealed marked bilateral enophthalmos, poor lower eyelid apposition to the ocular surface, and patent nasolacrimal systems. Radiographic imaging demonstrated expanded orbital volumes with high arching orbital roofs, sequestered air under the eyelids, short, straight optic nerves, and expanded paranasal sinuses. Surgical intervention included insertion of mesh and block implants within the subperiosteal space of the orbital roof, resulting in correction of enophthalmos, improved lower eyelid apposition and resolution of tearing. However, new onset myopic astigmatism and bilateral ptosis were noted postoperatively and treated successfully with corrective spectacles and ptosis repair. Current literature has demonstrated the benefit of orbital roof implants through a upper eyelid crease incision. The authors present a case that supports the utility of this approach and addresses its potential complications, including postoperative-induced astigmatism/myopia and ptosis. PMID- 26866333 TI - Iodine-131 Therapy and Nasolacrimal Duct Obstructions: What We Know and What We Need to Know. AB - PURPOSE: The aims of the current review are to summarize the etiopathogenesis, symptomatology, management, complications, and outcomes of iodine-131-induced nasolacrimal duct obstructions, to propose a screening protocol and elucidate the potential avenues of future research. METHODS: The authors performed an electronic database (PubMed, MEDLINE, EMBASE, and Cochrane Library) search of all articles published in English on nasolacrimal duct obstructions following radioiodine therapy. These articles were reviewed along with their relevant cross references. Data reviewed included demographics, presentations, investigations, management, complications, and outcomes. In addition, based on relevant unanswered questions and current lacunae in literature, potential avenues for further research have been elucidated. RESULTS: The frequency of nasolacrimal duct obstruction is reported to range from 2.2% to 18% following I-131 therapy. They are mostly bilateral and noted in patients who receive more than 150 mCi radioiodine. Exact etiopathogenesis is unknown but radiotoxicity to lacrimal sac and nasolacrimal duct is believed to be mediated through a sodium-iodine symporter protein. Although uncommon, it is important to increase awareness among treating physicians and patients receiving radioiodine therapy about the potential side effect of nasolacrimal duct obstruction. Imaging modalities are useful adjuncts in the diagnosis. Dacryocystorhinostomy is the most common modality of management with good outcomes. CONCLUSIONS: Nasolacrimal duct obstruction following radioiodine treatment is a distinct clinical entity. Increased awareness would facilitate timely diagnosis, management, and an enhanced quality of life for the patients. PMID- 26866334 TI - Compliance With Protective Lens Wear in Anophthalmic Patients. AB - PURPOSE: To evaluate the frequency of protective lens wear by anophthalmic patients and identify factors that influence compliance. METHODS: An IRB approved descriptive retrospective chart review of patients undergoing surgery with the senior author (PLC) with an anophthalmic orbit and one remaining sighted eye. Results were tabulated and analyzed using age, indication for procedure, duration of visual symptoms, safety glasses wear, number of postoperative visits, and evidence of new trauma to the remaining eye. All patients underwent counseling on the importance of protective lens wear preoperatively and each subsequent visit. RESULTS: Etiologies for loss of the eye in the 132 study patients included trauma (33.3%), blind painful eye (33.3%), congenital disorders (14.4%), adult-onset malignancy (14.4%), and retinoblastoma (4.5%). At the final visit, protective lenses were worn in the following patterns: full-time (55.3%), frequently (11.4%), occasional (6%), and never (28.8%). The regular use of protective eyewear at last visit was more common in patients wearing glasses at presentation (79.7%), than in those who did not (32.9%; p <= 0.001). Increased number of office encounters correlated with more frequent use of protective eyewear (p <= 0.01). Patient age (p = 0.95), indication for surgery (p = 0.97), and duration of visual loss (p = 0.85) were not predictive of safety glasses wear. Three patients had evidence of subsequent ocular trauma to the remaining eye, with 2 having resultant decrease in acuity; none of these 3 patients wore safety glasses full time. CONCLUSIONS: A significant number of anopthalmic patients were not wearing protective lenses at presentation. Overall compliance was poor; but repeated education on the importance of safety glasses appears to improve compliance. Educating referring providers and primary care physicians about the importance of early and repeated counseling is vital to increasing compliance. PMID- 26866335 TI - Assessment of Cutaneous Melanoma by Use of Very- High-Frequency Ultrasound and Real-Time Elastography. AB - OBJECTIVE: The primary objective of this study was to evaluate the usefulness of very-high-frequency ultrasound as tool for assessment of skin melanoma by investigation of the correlation between the ultrasound measurement of the thickness of a melanoma and the histopathologically measured Breslow index. The secondary objective was to assess the potential role of real-time elastography in the preoperative evaluation of skin melanoma. SUBJECTS AND METHODS: The study included 42 cutaneous melanoma lesions in 39 adult subjects examined in the division of ultrasound of a department of radiology between September 2011 and January 2015. Gray-scale sonographic features at 40 MHz (thickness, echogenicity, contour) and real-time strain elastographic (qualitative and semiquantitative, strain ratio) characteristics were evaluated and compared with the pathologic results. RESULTS: The melanoma lesions had a homogeneous hypoechoic appearance with a regular contour and stiff or medium consistency. The mean difference between Breslow index and ultrasound thickness was -0.05 mm (95% CI, -0.24 to 0.13 mm), sustaining the absence of significant differences between these two measurements. A strong relation was identified between real-time elastographic appearance and strain ratio for the relations between lesion and hypodermis and between lesion and neighboring dermis (p < 0.002) or hypodermis. CONCLUSION: Our study showed that very-high-frequency ultrasound and real-time elastography can be useful examinations for comprehensive preoperative evaluation of cutaneous melanoma. PMID- 26866336 TI - Direct Comparison of Unenhanced and Contrast-Enhanced CT for Opportunistic Proximal Femur Bone Mineral Density Measurement: Implications for Osteoporosis Screening. AB - OBJECTIVE: For patients undergoing contrast-enhanced CT examinations that include the proximal femur, an opportunity exists for concurrent screening bone mineral density (BMD) measurement. We investigated the effect of IV contrast enhancement on CT-derived x-ray absorptiometry areal BMD measurement. MATERIALS AND METHODS: Our cohort included 410 adults (mean age, 65.3 +/- 10.0 years; range, 49-95 years) who underwent split-bolus CT urography at 120 kVp. Areal femoral neck BMD in g/cm(2) was measured on both unenhanced and contrast-enhanced CT series with asynchronous phantom calibration. Constant offset and multiplicative factor corrections for the contrast-enhanced series were derived from the Bland-Altman plot linear regression slopes. RESULTS: Mean unenhanced and contrast-enhanced areal femoral neck BMD values were 0.681 +/- 0.118 and 0.713 +/- 0.123 g/cm(2), respectively. The SD of the distribution of residuals for the constant offset and multiplicative model corrections were 0.0232 and 0.0231, respectively. The constant offset correction associated with contrast enhancement was 0.032 +/- 0.023 g/cm(2), which corresponds to 0.29 +/- 0.21 T-score units using the CT derived x-ray absorptiometry young normal areal femoral neck BMD reference SD of 0.111 g/cm(2). CONCLUSION: For the purposes of opportunistic osteoporosis screening, contrast-enhanced abdominopelvic CT studies are equivalent to unenhanced CT and can therefore be used for femoral neck BMD assessment. This measure could greatly enhance osteoporosis screening. PMID- 26866338 TI - Patient Recall Imaging in the Ambulatory Setting. AB - OBJECTIVE: Recalling a patient to repeat a radiology examination is an adverse and, in certain cases, preventable event. Our objectives were to assess the rate of patient recalls for all imaging performed in the outpatient setting at our institution and to characterize the underlying reasons for the recalls. MATERIALS AND METHODS: We performed a retrospective review of all repeat imaging requests for an inadequate initial imaging study between January 2012 and March 2015. RESULTS: We identified 100 recall requests (mean, 2.6 requests per month), for an overall recall rate of approximately 1 in 8046 ambulatory studies and 1 in 1684 MRI studies. Nearly all recalls (98%) involved adults. A total of 95% of the recalls were for MRI studies. The most common reason for a patient recall request was an incomplete examination, making up 24% of all requests. The other causes were inadequate coverage of the area of interest (22%), protocoling errors (20%), poor imaging quality (15%), additional imaging to clarify a finding (11%), insufficient contrast visualization (7%), and incorrect patient information (1%). CONCLUSION: We found that patient recalls for imaging in the outpatient setting at our institution are not common. When recalls did occur, they were most often related to the acquisition of MR images. Improved technologist education on MRI protocoling and enhanced communication between ordering clinicians and radiologists to clarify the purpose of imaging might reduce the need for repeat ambulatory imaging. PMID- 26866337 TI - Incidence of Contrast-Induced Nephropathy After Renal Graft Catheter Arteriography Using Iodine-Based Contrast Medium. AB - OBJECTIVE: The objective of our study was to assess the incidence of contrast induced nephropathy (CIN), dialysis, and graft loss after direct intraarterial infusion of iodine-based contrast medium (CM) in renal allograft recipients. MATERIALS AND METHODS: One hundred patients underwent renal graft catheter arteriography between 2006 and 2014. CIN was defined as an increase in serum creatinine value of 0.5 mg/dL or more above the creatinine value before arteriography. CIN could be assessed in 37 patients with creatinine levels obtained before arteriography and 24-72 hours after arteriography. Dialysis requirement and renal allograft loss at 30 days after the procedure were recorded in all 100 patients. RESULTS: In the 37 patients who could be assessed for CIN, three patients (8%) met the criteria for CIN. In a subgroup analysis, there was an increased incidence of CIN in patients undergoing angiography alone (25%) compared with those in the angioplasty and stenting group (0%) (p = 0.028). At 30 days after the procedure, none (0/100) of the patients required dialysis or had graft failure. CONCLUSION: In a cohort of patients with a single renal allograft undergoing renal graft catheter arteriography using iodine-based CM, the overall incidence of CIN was low and no major adverse outcomes were noted at 30 days after the procedure. However, in a subgroup analysis, the patients who underwent arteriography alone-that is, without angioplasty or stenting-had a statistically significant higher rate of CIN. PMID- 26866339 TI - Safety and Outcomes of Percutaneous Biopsy of 61 Hepatic Adenomas. AB - OBJECTIVE: Given the recent classification of hepatic adenoma (HA) into subtypes and recognition of imperfect specificity of MRI to differentiate HA from focal nodular hyperplasia (FNH), there is a resurgent interest in the role of biopsy to diagnose HA. The purpose of this study was to determine the safety and outcomes of biopsy of HAs. MATERIALS AND METHODS: A retrospective review of the electronic medical records of all patients who underwent hepatic mass biopsy revealing HA from 2000 through 2013 was performed. The biopsy procedure parameters were evaluated. Complications were graded using the Common Terminology Criteria for Adverse Events. Pathology-specific outcomes related to the diagnosis of HA were assessed. RESULTS: Sixty patients (52 women and eight men) were identified with a mean age of 42 +/- 13 (SD) years and a mean follow-up of 2.3 +/- 3.0 years after biopsy. One patient had two HAs biopsied during the same procedure, resulting in a total of 61 biopsy-proven HAs. Of the 60 patients, one patient (2%) had a single major complication, which involved bleeding that resulted in a blood transfusion, and six patients (10%) had a minor complication. A total of six (10%) discordant biopsy results were found: Four biopsy-proven HAs (7%) revealed FNH on surgical resection or repeat biopsy, one HA (2%) showed well differentiated hepatocellular carcinoma (HCC) at subsequent biopsy, and one HA (2%) showed findings suggestive of HCC on follow-up imaging. CONCLUSION: Complications after biopsy of HAs are uncommon. Although uncommon, discordant pathology results between biopsy and surgical resection may occur. PMID- 26866340 TI - Systematic Evaluation of Radiation Dose Reduction in CT Studies of Body Packers: Accuracy Down to Submillisievert Levels. AB - OBJECTIVE: The objective of this study was to systematically evaluate the accuracy of abdominal CT performed at different radiation dose levels for the detection of body packs in human cadavers, in comparison with the accuracy of abdominal radiography. MATERIALS AND METHODS: In this study, differing numbers of body packs (range, 0-20) were placed in the alimentary tract of human cadavers and then underwent imaging with abdominal radiography and with CT performed at different radiation dose levels (ranging from the standard abdominal CT dose to the technical minimum dose). Depiction of body packs on abdominal radiographs and on each CT scan was assessed by two independent blinded radiologists, and the accuracy of detection of body packs was calculated. The radiation dose associated with abdominal radiography was measured, and the effective radiation dose associated with CT was estimated. RESULTS: The mean (+/- SD) effective radiation dose for abdominal radiography was 1.4 +/- 0.3 mSv, whereas the mean effective dose of CT ranged from 0.1 to 9.6 mSv. Interobserver agreement for body pack detection was moderate (kappa = 0.51) for abdominal radiography and good (kappa = 0.72-0.85) for CT. In a per-body pack analysis, abdominal radiography depicted 42% of the body packs with a sensitivity of 71% and a specificity of 100%. When performed at radiation dose levels of 0.6 mSv or greater, CT correctly detected all body packs. In per-person analysis, the sensitivity and specificity of CT for the correct detection of at least one body pack per cadaver was 100% for all radiation dose levels. CONCLUSION: CT performed at a dose of 0.6 mSv can be used for the detection of body packs. With a sensitivity and specificity of 100%, CT is superior to abdominal radiography in terms of reliability, associated radiation dose, and accuracy of detection. PMID- 26866341 TI - Detecting Regional Myocardial Abnormalities in Patients With Wolff-Parkinson White Syndrome With the Use of ECG-Gated Cardiac MDCT. AB - OBJECTIVE: Myocardial dyskinesia caused by the accessory pathway and related reversible heart failure have been well documented in echocardiographic studies of pediatric patients with Wolff-Parkinson-White (WPW) syndrome. However, the long-term effects of dyskinesia on the myocardium of adult patients have not been studied in depth. The goal of the present study was to evaluate regional myocardial abnormalities on cardiac CT examinations of adult patients with WPW syndrome. MATERIALS AND METHODS: Of 74 patients with WPW syndrome who underwent cardiac CT from January 2006 through December 2013, 58 patients (mean [+/- SD] age, 52.2 +/- 12.7 years), 36 (62.1%) of whom were men, were included in the study after the presence of combined cardiac disease was excluded. Two observers blindly evaluated myocardial thickness and attenuation on cardiac CT scans. On the basis of CT findings, patients were classified as having either normal or abnormal findings. We compared the two groups for other clinical findings, including observations from ECG, echocardiography, and electrophysiologic study. RESULTS: Of the 58 patients studied, 16 patients (27.6%) were found to have myocardial abnormalities (i.e., abnormal wall thinning with or without low attenuation). All abnormal findings corresponded with the location of the accessory pathway. Patients with abnormal findings had statistically significantly decreased left ventricular function, compared with patients with normal findings (p < 0.001). The frequency of regional wall motion abnormality was statistically significantly higher in patients with abnormal findings (p = 0.043). However, echocardiography documented structurally normal hearts in all patients. CONCLUSION: A relatively high frequency (27.6%) of regional myocardial abnormalities was observed on the cardiac CT examinations of adult patients with WPW syndrome. These abnormal findings might reflect the long-term effects of dyskinesia, suggesting irreversible myocardial injury that ultimately causes left ventricular dysfunction. PMID- 26866342 TI - Gastric Wall Fatty Infiltration in Patients Without Overt Gastrointestinal Disease. AB - OBJECTIVE: The purpose of this study was to evaluate the frequency of gastric wall fatty infiltration in patients without overt gastrointestinal disease. MATERIALS AND METHODS: A retrospective study included patients who underwent unenhanced MDCT for renal colic. Two radiologists reviewed all of the images and evaluated for the presence of gastric wall fatty infiltration. The following patient characteristics were also recorded: sex, age, body mass index, total and visceral fat area, and presence of colic or ileal fat halo sign, or hepatic steatosis. A t test and Fisher test were used to compare the results between patients with and patients without gastric wall fatty infiltration. RESULTS: Gastric wall fatty infiltration was present in 25 of 120 (21%) patients in the study. Mean age, weight, body mass index, visceral and total fat areas, proportion of hepatic steatosis, number of men, and frequency of the presence of colic and ileal fat halo signs were significantly higher among patients with gastric wall fatty infiltration than in those without infiltration. CONCLUSION: Gastric wall fatty infiltration was significantly more frequent in men older than 45 years and patients with a body mass index greater than 25. It may represent a normal finding, but its relation to other pathologic conditions related to obesity remains to be explored. PMID- 26866343 TI - Corticosteroid implants for chronic non-infectious uveitis. AB - BACKGROUND: Uveitis is a term used to describe a heterogeneous group of intraocular inflammatory diseases of the anterior, intermediate, and posterior uveal tract (iris, ciliary body, choroid). Uveitis is the fifth most common cause of vision loss in high-income countries, accounting for 5% to 20% of legal blindness, with the highest incidence of disease in the working-age population.Corticosteroids are the mainstay of acute treatment for all anatomical subtypes of non-infectious uveitis and can be administered orally, topically with drops or ointments, by periocular (around the eye) or intravitreal (inside the eye) injection, or by surgical implantation. OBJECTIVES: To determine the efficacy and safety of steroid implants in people with chronic non-infectious posterior uveitis, intermediate uveitis, and panuveitis. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled trials.com) (last searched 15 April 2013), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for studies. We last searched the electronic databases on 6 November 2015.We also searched reference lists of included study reports, citation databases, and abstracts and clinical study presentations from professional meetings. SELECTION CRITERIA: We included randomized controlled trials comparing either fluocinolone acetonide (FA) or dexamethasone intravitreal implants with standard-of-care therapy with at least six months of follow-up after treatment. We included studies that enrolled participants of all ages who had chronic non-infectious posterior uveitis, intermediate uveitis, or panuveitis with vision that was better than hand-motion. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed studies for inclusion. Two review authors independently extracted data and assessed the risk of bias for each study. MAIN RESULTS: We included data from two studies (619 eyes of 401 participants) that compared FA implants with standard-of-care therapy. Both studies used similar standard-of-care therapy that included administration of prednisolone and, if needed, immunosuppressive agents. The studies included participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States. We assessed both studies at high risk of performance and detection bias.Only one study reported our primary outcome, recurrence of uveitis at any point during the study through 24 months. The evidence, judged as moderate quality, showed that a FA implant probably prevents recurrence of uveitis compared with standard-of-care therapy (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.14 to 0.59; 132 eyes). Both studies reported safety outcomes, and moderate-quality evidence showed increased risks of needing cataract surgery (RR 2.98, 95% CI 2.33 to 3.79; 371 eyes) and surgery to lower intraocular pressure (RR 7.48, 95% CI 3.94 to 14.19; 599 eyes) in the implant group compared with standard-of-care therapy through two years of follow-up. No studies compared dexamethasone implants with standard-of-care therapy. AUTHORS' CONCLUSIONS: After considering both benefits and harms reported from two studies in which corticosteroids implants were compared with standard-of-care therapy, we are unable to conclude that the implants are superior to traditional systemic therapy for the treatment of non-infectious uveitis. These studies exhibited heterogeneity in design and outcomes that measured efficacy. Pooled findings regarding safety outcomes suggest increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy. PMID- 26866344 TI - Occupational HIV Transmission Among Male Adult Film Performers - Multiple States, 2014. AB - In 2014, the California Department of Public Health was notified by a local health department of a diagnosis of acute human immunodeficiency virus (HIV) infection* and rectal gonorrhea in a male adult film industry performer, aged 25 years (patient A). Patient A had a 6-day history of rash, fever, and sore throat suggestive of acute retroviral syndrome at the time of examination. He was informed of his positive HIV and gonorrhea test results 6 days after his examination. Patient A had a negative HIV-1 RNA qualitative nucleic acid amplification test (NAAT)(?) 10 days before symptom onset. This investigation found that during the 22 days between the negative NAAT and being informed of his positive HIV test results, two different production companies directed patient A to have condomless sex with a total of 12 male performers. Patient A also provided contact information for five male non-work-related sexual partners during the month before and after his symptom onset. Patient A had additional partners during this time period for which no locating information was provided. Neither patient A nor any of his interviewed sexual partners reported taking HIV preexposure prophylaxis (PrEP). Contact tracing and phylogenetic analysis of HIV sequences amplified from pretreatment plasma revealed that a non-work-related partner likely infected patient A, and that patient A likely subsequently infected both a coworker during the second film production and a non-work-related partner during the interval between his negative test and receipt of his positive HIV results. Adult film performers and production companies, medical providers, and all persons at risk for HIV should be aware that testing alone is not sufficient to prevent HIV transmission. Condom use provides additional protection from HIV and sexually transmitted infections (STIs). Performers and all persons at risk for HIV infection in their professional and personal lives should discuss the use of PrEP with their medical providers. PMID- 26866346 TI - Dissociating spatial and spatiotemporal aspects of navigation ability in chronic stroke patients. AB - OBJECTIVE: The notion of distinguishable processing mechanisms for spatial and spatiotemporal information has largely been neglected in the context of navigation. Only a recent neuropsychological case study has provided initial evidence for the idea that these elements can be differentiated at a functional level. The aim of the current study was therefore to critically verify this double dissociation by adopting a systematic, large-scale approach. METHOD: Sixty five chronic stroke patients and 60 matched healthy controls watched a route through a realistic virtual environment. They were assessed on their knowledge of this route in 4 different tasks after the learning phase. Performance on the scene recognition and route continuation tasks was taken as an indication of knowledge of the spatial route aspects. By contrast, spatiotemporal knowledge of the route was assessed in the route order and route progression tasks. RESULTS: Based on single case statistics, 6 patients showed an exceptionally large difference in their performance on the spatial and spatiotemporal tasks. Moreover, 2 patients satisfied formal criteria for a classical dissociation. CONCLUSIONS: Our findings showed that spatial and spatiotemporal performance was closely associated in most patients. Nonetheless, the study also provided partial support for the notion of separate space- and time-based processing mechanisms in the context of navigation. This distinction is of particular relevance to the investigation into the cognitive structure underlying navigation behavior. (PsycINFO Database Record PMID- 26866347 TI - Differential processing of hierarchical visual stimuli in young and older healthy adults: An event-related potentials (ERP) study. AB - OBJECTIVE: In tasks involving hierarchical stimuli, young subjects typically show faster RTs and higher accuracy rates in discriminating target stimuli at the global level than at the local level. This pattern of performance is called the global precedence effect (GPE). As individuals age, this patterns shifts to a local precedence effect (LPE). The purpose of this study was to determine whether the decline in GPE in older adults may be due to impairment of grouping processes. METHOD: The authors recorded event-related potentials (ERP) while young and elderly subjects performed a global/local task in response to hierarchical stimuli, and they focused on the P300 component as an index of grouping processes. RESULTS: Compared to young subjects, elderly individuals showed a lower rate of correct discrimination in global processing conditions, but a higher rate of correct responses in local processing conditions, confirming a shift from a GPE to a LPE during aging. Interestingly, the P300 amplitude increased selectively during global processing in young adults but was not modulated by processing level in older participants. By contrast, the modulation of the early component N2 as a function of precedence level remained preserved in older subjects. CONCLUSION: The results suggest that the precedence level may depend on early processes that are unaffected during aging. This may explain the preservation of local precedence effect in elderly individuals. However, global processing may depend on extra attentional processing occurring at later stages. The alteration of later processing may explain the decline in global precedence during aging. (PsycINFO Database Record PMID- 26866345 TI - Evaluating the consequences of impaired monitoring of learned behavior in attention-deficit/hyperactivity disorder using a Bayesian hierarchical model of choice response time. AB - OBJECTIVE: Performance monitoring deficits have been proposed as a cognitive marker involved in the development of attention-deficit/hyperactivity disorder (ADHD), but it is unclear whether these deficits cause impairment when established action sequences conflict with environmental demands. The current study applies a novel data-analytic technique to a well-established sequence learning paradigm to investigate reactions to disruption of learned behavior in ADHD. METHOD: Children (ages 8-12) with and without ADHD completed a serial reaction time task in which they implicitly learned an 8-item sequence of keypresses over 5 training blocks. The training sequence was replaced with a novel sequence in a transfer block, and returned in 2 subsequent recovery blocks. Response time (RT) data were fit by a Bayesian hierarchical version of the linear ballistic accumulator model, which permitted the dissociation of learning processes from performance monitoring effects on RT. RESULTS: Sequence-specific learning on the task was reflected in the systematic reduction of the amount of evidence required to initiate a response, and was unimpaired in ADHD. When the novel sequence onset, typically developing children displayed a shift in their attentional state while children with ADHD did not, leading to worse subsequent performance compared to controls. CONCLUSIONS: Children with ADHD are not impaired in learning novel action sequences, but display difficulty monitoring their implementation and engaging top-down control when they become inadequate. These results support theories of ADHD that highlight the interactions between monitoring processes and changing cognitive demands as the cause of self regulation and information-processing problems in the disorder. (PsycINFO Database Record PMID- 26866348 TI - Decomposing card-sorting performance: Effects of working memory load and age related changes. AB - OBJECTIVE: The Wisconsin Card Sorting Test (WCST) is often regarded as a prototypical neuropsychological test of set-shifting ability. However, it has been proposed that WCST performance involves cognitive processes other than set shifting, such as set maintenance and rule inference. Distinguishing between these processes is necessary for the meaningful interpretation of WCST performance deficits in neuropsychological populations. In the present studies, we aimed to concurrently measure processes of set shifting, set maintenance and rule inference in a computerized version of the WCST, and to dissociate these processes based on their dependence on working memory capacity. METHOD AND RESULTS: In Study 1, we manipulated the number of card-sorting rules to vary the demands placed on working memory-dependent processes of rule inference. As predicted, integration errors as a novel measure of rule-inference efficiency were selectively affected by increasing the number of rules from 3 to 4. In Study 2, we examined age-related changes in set shifting, set maintenance, and rule inference. We found a specific association between age and integration errors, indicating that rule inference, but not set shifting or set maintenance, is affected in older individuals. CONCLUSIONS: Rule inference on WCST-like card sorting tasks appeared to be selectively impaired when the amount of information to be integrated in working memory increases or when working memory capacity is reduced (as in older individuals). Our findings indicate that measuring integration errors as an index of a distinct rule-inference process can improve the understanding and interpretability of WCST performance. (PsycINFO Database Record PMID- 26866349 TI - [Healthcare in One's Own Home or Outside: A Comparison of the Health Status of Family Caregivers]. AB - The GEDA-Survey 2012 is a representative, nationwide survey conducted by means of computer-assisted telephone interviews (CATI) between March 2012 and March 2013 by the Robert Koch Institute with 19 294 completed interviews. A total of 1 219 persons tending to the needs of a care-dependent person responded to questions about sex, age and health status. Using the statistics software "SPSS", the GEDA data were evaluated descriptively and finally visualized with "Microsoft Office". The survey results reveal that 47,2% of family caregivers from this cohort are between 45 and 64 years old. This cohort had more female caregivers (62,8%) than males (37,2%). Comparing the frequency of information on health status in 3 age groups, our survey indicated that persons tending to an individual outside their own homes assessed their health status to be better than those caring for individuals in their own homes. PMID- 26866350 TI - Elevated interleukin-8 in bile of patients with primary sclerosing cholangitis. AB - BACKGROUND & AIMS: To better understand the pathogenesis of primary sclerosing cholangitis, anti- and pro-inflammatory factors were studied in bile. METHODS: Ductal bile of PSC patients (n = 36) and controls (n = 20) was collected by endoscopic retrograde cholangiography. Gallbladder bile was collected at liver transplantation. Bile samples were analysed for cytokines, FGF19 and biliary lipids. Hepatobiliary tissues of PSC and non-PSC patients (n = 8-11 per patient group) were collected at transplantation and were analysed for IL8 and FGF19 mRNA expression and IL8 localization. The effect of IL8 on proliferation of primary human cholangiocytes and expression of pro-fibrotic genes was studied. RESULTS: In PSC patients, median IL8 in ductal bile was 6.6 ng/ml vs. 0.24 ng/ml in controls. Median IL8 in gallbladder bile was 7.6 ng/ml in PSC vs. 2.2 and 0.3 ng/ml in two control groups. IL8 mRNA in PSC gallbladder was increased and bile ducts stained positive for IL8. In vitro, IL8 induced proliferation of primary human cholangiocytes and increased the expression of pro-fibrotic genes. CONCLUSION: Elevation of IL8 in bile of PSC patients, collected at different stages of disease, indicates an ongoing inflammatory stimulus that drives IL8 production. This challenges the idea that advanced PSC is a burned-out disease, and calls for reconsideration of anti-inflammatory therapy in PSC. PMID- 26866352 TI - Lithium-titanate-nanotube-supported WO3 for enhancing transmittance contrast in electrochromics. AB - Lithium titanate nanotubes (Li-TNTs) have been successfully synthesized. The inner and outer diameters of the nanotubes are 5 nm and 8 nm with an interlayer spacing of 0.83 nm. The nanotubes were in accordance with the Li1.81H0.19Ti2O5 . xH2O phase. The chemical component was Li0.9H1.1Ti2O5 . H2O as determined by ICP AES. The Li-TNT-supported WO3 nanoparticle (WO3/Li-TNTs) thin film was prepared onto ITO glass via spin-coating and then fabricated with an electrochromic device. The Li ion diffusion coefficient in the WO3/Li-TNT film was 6.1 * 10(-10) cm(2) s(-1), which is eight times higher than that for the pure WO3 film. The transmittance contrast of the pure WO3-based ECD was 53.3% at 600 nm. However, this increased to 74.1% for the WO3/Li-TNT-based ECD. Meanwhile, the color switching times of the WO3/Li-TNT-based ECD were apparently shorter than the ones for the WO3-based ECD. PMID- 26866351 TI - Pathways Between Discrimination and Quality of Life in Patients with Type 2 Diabetes. AB - BACKGROUND: Discrimination is a social determinant that has been linked to poor physical and mental health outcomes. This study aimed to examine the pathway whereby discrimination influences quality of life in patients with type 2 diabetes. SUBJECTS AND METHODS: Six hundred fifteen patients were recruited from two adult primary care clinics in the southeastern United States. Measures included perceived discrimination, perceived stress, social support, and social cohesion and were based on a theoretical model for the pathways by which perceived discrimination influences mental and physical health. Quality of life was measured using the SF-12 questionnaire. RESULTS: The final model [chi(2)(106) = 157.35, P = 0.009, R(2) = 0.99, root mean square error of approximation = 0.03, comparative fit index = 0.99] indicates direct effects of higher perceived stress (r = -1.02, P < 0.05) and lower social support (r = 0.36, P < 0.001) significantly related to decreased mental health component score (MCS) of quality of life. Discrimination and social cohesion were not significantly directly related to MCS. However, higher discrimination (r = 0.47, P < 0.001), higher social cohesion (r = 0.14, P < 0.05), and lower social support (r = -0.43, P < 0.001) were significantly directly related to increased stress. No significant paths were found for the physical component score of quality of life. CONCLUSIONS: Perceived discrimination was significantly associated with stress and served as a pathway to influence the mental health component of quality of life (MCS). Social support had a direct and an indirect effect on MCS through a negative association with stress. These results suggest that future interventions should be developed to decrease stress and increase social support surrounding discrimination to improve the MCS of quality of life in patients with diabetes. PMID- 26866353 TI - Gene Expression Profiling Supports the Neural Crest Origin of Adult Rodent Carotid Body Stem Cells and Identifies CD10 as a Marker for Mesectoderm-Committed Progenitors. AB - Neural stem cells (NSCs) are promising tools for understanding nervous system plasticity and repair, but their use is hampered by the lack of markers suitable for their prospective isolation and characterization. The carotid body (CB) contains a population of peripheral NSCs, which support organ growth during acclimatization to hypoxia. We have set up CB neurosphere (NS) cultures enriched in differentiated neuronal (glomus) cells versus undifferentiated progenitors to investigate molecular hallmarks of cell classes within the CB stem cell (CBSC) niche. Microarray gene expression analysis in NS is compatible with CBSCs being neural crest derived-multipotent progenitor cells able to sustain CB growth upon exposure to hypoxia. Moreover, we have identified CD10 as a marker suitable for isolation of a population of CB mesectoderm-committed progenitor cells. CD10 + cells are resting in normoxia, and during hypoxia they are activated to proliferate and to eventually complete maturation into mesectodermal cells, thus participating in the angiogenesis necessary for CB growth. Our results shed light into the molecular and cellular mechanisms involved in CBSC fate choice, favoring a potential use of these cells for cell therapy. Stem Cells 2016;34:1637-1650. PMID- 26866354 TI - Myxoid Leiomyosarcoma of the Uterus: A Clinicopathologic Analysis of 30 Cases and Review of the Literature With Reappraisal of Its Distinction From Other Uterine Myxoid Mesenchymal Neoplasms. AB - Myxoid leiomyosarcoma (mLMS) of the uterus is a rare neoplasm; thus, knowledge of its clinical behavior and morphology remains limited. We therefore reviewed 30 cases initially diagnosed as uterine mLMS to better characterize its clinicopathologic features. Diagnosis was confirmed in 25 subjects (average age 51.5 y), of whom 80% were stage 1 at presentation. The average tumor size was 10.8 cm. An infiltrative tumor border was observed microscopically in 24 cases (96%); the border in 1 case could not be assessed. Fourteen cases (56%) had >10 mitoses per 10 high-power fields, 8 (32%) had between 2 and 10, and 3 cases (12%) had <2 mitoses. Geographic tumor necrosis and moderate to severe nuclear pleomorphism were seen concurrently in 12 cases (48%). All tumors expressed smooth muscle markers. Estrogen receptor was expressed in 29.4% of cases. Eighteen of 21 cases (85.7%) were negative for ALK by immunohistochemistry. Follow-up information was available in 18 subjects: 8 died of disease, 6 were alive with local and/or distant recurrence, and 4 were alive with no evidence of disease. Individuals who died of disease tended to have tumors with >10 mitoses per 10 high-power fields. Among cases with >=5-year follow-up, overall survival was 11.1%, significantly worse compared with reported survival rates for conventional LMS. The initial diagnosis of mLMS was revised in 5 cases. Four had a distinctive loose myxoid appearance, nuclei with vesicular chromatin, and ALK positivity by immunohistochemistry, suggesting, suggesting inflammatory myofibroblastic tumor. This diagnosis was confirmed by in situ hybridization in 2 cases. One additional myxoid tumor lacked smooth muscle or myofibroblastic features and could not be classified further. mLMS is an aggressive neoplasm characterized by infiltrative tumor borders and variability of other features (mitotic count, atypia, and necrosis). The differential diagnosis includes myxoid leiomyoma and inflammatory myofibroblastic tumor. Attention to distinguishing morphologic features and immunohistochemistry will aid in the interpretation. An illustrated algorithm with criteria for diagnosis is proposed. PMID- 26866355 TI - Basaloid Squamous Cell Carcinoma of the Anus Revisited. AB - Basaloid squamous cell carcinoma (SCC) of the anus, previously called cloacogenic carcinoma, is a subtype of SCC. There are very few data on the morphologic variation within basaloid SCC of the anus, which may contribute to misdiagnosis. We retrospectively evaluated cases originally diagnosed as basaloid SCC for histologic characterization. We retrieved and reviewed cases of basaloid SCC from 1994 to 2013. Ten (27%) cases were reclassified after review, including basal cell carcinoma (n=6), melanoma (n=2), and neuroendocrine carcinoma (n=2). The final group of basaloid SCC (n=27) showed a female predominance (median age=60 y; range, 42 to 92 y). Morphologically, basaloid SCC could be categorized into 4 groups: transitional carcinoma like (n=10), basaloid with peripheral palisade (n=13), adenoid cystic carcinoma like (n=3), and mucinous microcystic (n=1). In 19 cases the histologic patterns were pure and were mixed in the remainder. CK5/6, p16, and high-risk HPV were positive in all cases (n=27). SOX2 was positive in 18/22 cases. Clinical follow-up was available on 60% of cases; 9 patients (53%) developed local recurrence or metastasis, and 5 (29%) died of disease. Basaloid SCC of the anus is characterized by 4 major histologic patterns and is consistently HPV driven. PMID- 26866356 TI - Protective Effect of Dihydromyricetin Against Lipopolysaccharide-Induced Acute Kidney Injury in a Rat Model. AB - BACKGROUND The present study investigated the effect of dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced acute kidney injury in a rat model. MATERIAL AND METHODS Kidney injury was induced in male Sprague-Dawley rats by injection of LPS through the tail vein. The rats were treated with 5 ug/kg body weight DHM within 12 h of the LPS administration. The urine of the rats was collected over a period of 48 h for determination of calcium and creatinine concentrations. Blood urea nitrogen in the serum was analyzed using a BC-2800 Vet Animal Auto Biochemistry Analyzer. On day 3 after treatment, the rats were sacrificed to extract the kidneys. RESULTS Treatment of the endotoxemia rats with DHM caused a significant (P<0.05) decrease in the level of kidney injury molecule-1 and blood urea nitrogen. DHM treatment significantly (P<0.05) decreased the level of calcium in the kidney tissues compared to those of the untreated endotoxemia rats. The level of malonaldehyde (MDA) in the kidney tissues was significantly reduced in the endotoxemia rats by DHM treatment. The results from immunohistochemistry reveled a significant decrease in the expression of osteopontin (OPN) and CD44 levels. The endotoxemia rats showed significantly higher levels of TUNEL-positive stained nuclei compared to the normal controls. However, treatment of the endotoxemia rats with DHM resulted in a significant decrease in the population of TUNEL positive cells. CONCLUSIONS DHM may be a promising candidate for the treatment of acute kidney injury. PMID- 26866357 TI - Erosive Monoarthritis of the Wrist Secondary to Coccidioides Immitis Infection. PMID- 26866358 TI - Using a wrap skirt to improve the pelvic examination experience. AB - INTRODUCTION: The study aims were to analyze the experience of women and their physicians of nakedness when moving between changing room and examination chair and during pelvic examination itself, and to assess the protective benefit of a wrap skirt in alleviating the associated discomfort and vulnerability. MATERIAL AND METHODS: We offered 1000 women a wrap skirt for pelvic examination and asked them to complete a post-procedure questionnaire. Physicians were invited to complete a similar but separate questionnaire. Data were analyzed using chi squared contingency tables. RESULTS: A total of 425 women (43%, age 15-78 years) completed the questionnaire; 51% felt uncomfortable and embarrassed during the examination, Muslim women significantly more so (p < 0.001). Most women (n = 255; 58%) rated the wrap skirt a significant improvement; 69% requested it for future examinations, significantly more so if the physician was male rather than female (66% vs. 54%, p = 0.003). Even the one-third of women experiencing no discomfort reported improvement. Most examiners (n = 45; 56%) found the wrap skirt beneficial; 31 (38%) were unconvinced. CONCLUSIONS: Pelvic examination as practiced in many countries, on women naked from the waist down throughout, causes unnecessary embarrassment. A simple protective measure, such as a wrap skirt, significantly alleviates the discomfort and sense of vulnerability associated with nakedness. PMID- 26866359 TI - Activated mesoporous carbon nanofibers fabricated using water etching-assisted templating for high-performance electrochemical capacitors. AB - Activated mesoporous carbon nanofibers (AMCNFs) are synthesized by a sequential process of electrospinning, water etching-assisted templating, and acid treatment. Their morphologies, crystal structures, melting behavior, chemical bonding states, surface properties, and electrochemical performance are investigated for three different polyacrylonitrile (PAN) to polyvinylpyrrolidone (PVP) weight ratios - PAN : PVP = 8 : 2, 7 : 3, and 6 : 4. Compared to other samples, the AMCNFs with an optimum weight ratio of 6 : 4 show the highest specific surface area of 692 m(2) g(-1), a high volume percentage of mesopores of 43.9%, and an increased amount of carboxyl groups (10.5%). This results in a high specific capacitance of 207 F g(-1), a high-rate capability with a capacitance retention of 93%, a high energy density of 24.8-23.1 W h kg(-1), and an excellent cycling durability of up to 3000 cycles. The electrochemical performance improvement can be explained by the combined effect of the high surface area relative to the increased electrical double-layers, the high volume fraction of mesopores relative to shorter diffusion routes and low resistance pathways for ions, and the increased amount of carboxyl groups on the CNF surface relative to enhanced wettability. PMID- 26866360 TI - Cholinergic mechanisms of the context preexposure facilitation effect in adolescent rats. AB - The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which context learning, context-shock association, and expression of context conditioning occur in 3 separate phases-preexposure, training, and testing. During the preexposure phase, the CPFE is disrupted by hippocampal NMDA receptor blockade in juvenile rats (Schiffino et al., 2011), and a similar deficit is seen with a subcutaneous injection of the muscarinic receptor antagonist, scopolamine, in adult mice (Brown, Kennard, Sherer, Comalli, & Woodruff-Pak, 2011). As a foundation for further developmental research, the present study examined the role of cholinergic function in the CPFE in adolescent rats during each phase of the CPFE protocol. In Experiment 1, an i.p injection of either 0.5 or 1.0 mg/kg dose of scopolamine administered prior to all 3 phases of the CPFE protocol impaired the CPFE. Experiment 2 further showed that a 0.5 mg/kg injection prior to just 1 of the 3 phases of the CPFE also disrupted contextual fear conditioning. We further showed that the CPFE is impaired by localized scopolamine infusions into dorsal hippocampus on the preexposure day (Experiment 3a), training day (Experiment 3b), and test day (Experiment 3c). These findings demonstrate a role of cholinergic signaling in hippocampus during each of the 3 phases of the CPFE in adolescent rats. Implications for the development and neural basis of the CPFE are discussed. (PsycINFO Database Record PMID- 26866361 TI - The bidirectional relation between emotional reactivity and sleep: From disruption to recovery. AB - Sleep disturbances are highly prevalent and greatly affect consecutive emotional reactivity, while sleep quality itself can be strongly affected by reactions to previous emotional events. In this review, we shed light on this bidirectional relation through examples of pathology: insomnia and bipolar disorder. We show that both experimental sleep deprivation and insomnia are related to increased emotional reactivity and increased amygdala activation upon emotional stimuli presentation, and that particularly Rapid Eye Movement (REM) sleep is important for emotional processing and reorganization of emotion-specific brain activity. Increased emotional reactivity affects REM sleep quality and sleep spindles, while REM sleep is particularly affected in insomnia, possibly related to condition-specific hyperarousal levels. Normal sleep onset deactivation of brain regions important for emotional processing (amygdala, anterior cingulate cortex (ACC)) is further affected in insomnia. In bipolar disorder, sleep disturbances are common in both symptomatic and nonsymptomatic phases. Both amygdala and ACC volume and function are affected in bipolar disorder, with the ACC showing phase dependent resting state activity differences. Deficient Gamma-aminobutyric acid (GABA) GABA-ergic activity of this region might play a role in sleep disturbances and their influence on emotional reactivity, given the inhibitory role of GABA on brain activity during sleep and its deficiency in both bipolar disorder and insomnia. Promising findings of normalizing brain activity in both insomnia and bipolar disorder upon treatment may inspire a focus on treatment studies investigating the normalization of sleep, emotional reactivity, and their corresponding brain activity patterns. (PsycINFO Database Record PMID- 26866362 TI - Genomic Organization of Human Transcription Initiation Complexes. AB - A repertoire of transcription initiation factors engage the core promoter of mRNA genes to recruit RNA polymerase (Pol) II to initiate transcription, yet their precise spatial organization remains unclear. Using ChIP-exo, here we detail the interactions and genomic organization of initiation factors TBP, TFIIB, and Pol II at mRNA genes and within CpG islands. We find that when Pol II moves into a transcriptionally paused state, TBP/TFIIB remain at the promoter. We show that TBP and TFIIB bound to the core promoter at two separate, resolvable locations that coincided with sites of divergent transcription initiation. We also examine the precise binding of TBP at Pol III transcribed tRNA genes. We find that TBP crosslinked to tRNA genes in a similar manner as at Pol II transcribed genes. This comprehensive and high resolution genome-wide detection of the initiation machinery produces a consolidated view of transcription initiation events humans at Pol II coding and Pol III transcribed tRNA genes. PMID- 26866363 TI - Stage-Specific Changes in the Water, Na+, Cl- and K+ Contents of Organelles during Apoptosis, Demonstrated by a Targeted Cryo Correlative Analytical Approach. AB - Many studies have demonstrated changes in the levels of several ions during apoptosis, but a few recent studies have reported conflicting results concerning the changes in water content in apoptotic cells. We used a correlative light and cryo-scanning transmission electron microscopy method to quantify water and ion/element contents simultaneously at a nanoscale resolution in the various compartments of cells, from the onset to the end of apoptosis. We used stably transfected HeLa cells producing H2B-GFP to identify the stages of apoptosis in cells and for a targeted elemental analysis within condensed chromatin, nucleoplasm, mitochondria and the cytosol. We found that the compartments of apoptotic cells contained, on average, 10% more water than control cells. During mitochondrial outer membrane permeabilization, we observed a strong increase in the Na+ and Cl- contents of the mitochondria and a strong decrease in mitochondrial K+ content. During the first step in apoptotic volume decrease (AVD), Na+ and Cl- levels decreased in all cell compartments, but remained higher than those in control cells. Conversely, during the second step of AVD, Na+ and Cl- levels increased considerably in the nucleus and mitochondria. During these two steps of AVD, K+ content decreased steadily in all cell compartments. We also determined in vivo ion status during caspase-3 activity and chromatin condensation. Finally, we found that actinomycin D-tolerant cells had water and K+ contents similar to those of cells entering apoptosis but lower Na+ and Cl- contents than both cells entering apoptosis and control cells. PMID- 26866364 TI - Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial. AB - OBJECTIVE: The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity. METHODS: In this trial, 70 female patients with breast cancer who were candidates to receive doxorubicin were enrolled, from which 30 were selected randomly to receive carvedilol 6.25 mg daily during chemotherapy, with the rest receiving placebo as the control group. Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate. RESULTS: Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention, while there was a significant reduction in these parameters in the control group (all p values <0.001). Also, the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls (basal septal strain, p = 0.005, basal lateral strain, p = 0.001, basal inferior strain, p < 0.001, and basal anterior strain, p < 0.001); the same was true for the strain-rate parameters (the p values for basal septal, basal lateral, basal inferior and basal anterior strain rate were 0.037, 0.037, 0.002 and <0.001, respectively). CONCLUSION: This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity. Whether this prophylaxis should be considered as the preferred method needs further investigation. PMID- 26866365 TI - Expression of cagA, virB/D Complex and/or vacA Genes in Helicobacter pylori Strains Originating from Patients with Gastric Diseases. AB - In order to better understand pathogenicity of Helicobacter pylori, particularly in the context of its carcinogenic activity, we analysed expression of virulence genes: cagA, virB/D complex (virB4, virB7, virB8, virB9, virB10, virB11, virD4) and vacA in strains of the pathogen originating from persons with gastric diseases. The studies were conducted on 42 strains of H. pylori isolated from patients with histological diagnosis of non-atrophic gastritis-NAG (group 1, including subgroup 1 containing cagA+ isolates and subgroup 2 containing cagA- strains), multifocal atrophic gastritis-MAG (group 2) and gastric adenocarcinoma GC (group 3). Expression of H. pylori genes was studied using microarray technology. In group 1, in all strains of H. pylori cagA+ (subgroup 1) high expression of the gene as well as of virB/D was disclosed, accompanied by moderate expression of vacA. In strains of subgroup 2 a moderate expression of vacA was detected. All strains in groups 2 and 3 carried cagA gene but they differed in its expression: a high expression was detected in isolates of group 2 and its hyperexpression in strains of group 3 (hypervirulent strains). In both groups high expression of virB/D and vacA was disclosed. Our results indicate that chronic active gastritis may be induced by both cagA+ strains of H. pylori, manifesting high expression of virB/D complex but moderate activity of vacA, and cagA- strains with moderate expression of vacA gene. On the other hand, in progression of gastric pathology and carcinogenesis linked to H. pylori a significant role was played by hypervirulent strains, manifesting a very high expression of cagA and high activity of virB/D and vacA genes. PMID- 26866367 TI - Machine learning and data mining in complex genomic data--a review on the lessons learned in Genetic Analysis Workshop 19. AB - In the analysis of current genomic data, application of machine learning and data mining techniques has become more attractive given the rising complexity of the projects. As part of the Genetic Analysis Workshop 19, approaches from this domain were explored, mostly motivated from two starting points. First, assuming an underlying structure in the genomic data, data mining might identify this and thus improve downstream association analyses. Second, computational methods for machine learning need to be developed further to efficiently deal with the current wealth of data.In the course of discussing results and experiences from the machine learning and data mining approaches, six common messages were extracted. These depict the current state of these approaches in the application to complex genomic data. Although some challenges remain for future studies, important forward steps were taken in the integration of different data types and the evaluation of the evidence. Mining the data for underlying genetic or phenotypic structure and using this information in subsequent analyses proved to be extremely helpful and is likely to become of even greater use with more complex data sets. PMID- 26866366 TI - Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects. AB - Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells. PMID- 26866368 TI - Optimal Timing of Delivery among Low-Risk Women with Prior Caesarean Section: A Secondary Analysis of the WHO Multicountry Survey on Maternal and Newborn Health. AB - OBJECTIVE: To investigate optimal timing of elective repeat caesarean section among low-risk pregnant women with prior caesarean section in a multicountry sample from largely low- and middle-income countries. DESIGN: Secondary analysis of a cross-sectional study. SETTING: Twenty-nine countries from the World Health Organization Multicountry Survey on Maternal and Newborn Health. POPULATION: 29,647 women with prior caesarean section and no pregnancy complications in their current pregnancy who delivered a term singleton (live birth and stillbirth) at gestational age 37-41 weeks by pre-labour caesarean section, intra-partum caesarean section, or vaginal birth following spontaneous onset of labour. METHODS: We compared the rate of short-term adverse maternal and newborn outcomes following pre-labour caesarean section at a given gestational age, to those following ongoing pregnancies beyond that gestational age. MAIN OUTCOME MEASURES: Severe maternal outcomes, neonatal morbidity, and intra-hospital early neonatal mortality. RESULTS: Odds of neonatal morbidity and intra-hospital early neonatal mortality were 0.48 (95% confidence interval [CI] 0.39-0.60) and 0.31 (95% CI 0.16-0.58) times lower for ongoing pregnancies compared to pre-labour caesarean section at 37 weeks. We did not find any significant change in the risk of severe maternal outcomes between pre-labour caesarean section at a given gestational age and ongoing pregnancies beyond that gestational age. CONCLUSIONS: Elective repeat caesarean section at 37 weeks had higher risk of neonatal morbidity and mortality compared to ongoing pregnancy, however risks at later gestational ages did not differ between groups. PMID- 26866369 TI - Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring. AB - Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function. Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random, exhibiting, for example, above-chance bidirectionality and an overrepresentation of certain triangular motifs. Additional evidence suggests a significant distance dependency to connectivity over a local scale of a few hundred microns, and particular patterns of synaptic turnover dynamics, including a heavy-tailed distribution of synaptic efficacies, a power law distribution of synaptic lifetimes, and a tendency for stronger synapses to be more stable over time. Understanding how many of these non-random features simultaneously arise would provide valuable insights into the development and function of the cortex. While previous work has modeled some of the individual features of local cortical wiring, there is no model that begins to comprehensively account for all of them. We present a spiking network model of a rodent Layer 5 cortical slice which, via the interactions of a few simple biologically motivated intrinsic, synaptic, and structural plasticity mechanisms, qualitatively reproduces these non-random effects when combined with simple topological constraints. Our model suggests that mechanisms of self-organization arising from a small number of plasticity rules provide a parsimonious explanation for numerous experimentally observed non random features of recurrent cortical wiring. Interestingly, similar mechanisms have been shown to endow recurrent networks with powerful learning abilities, suggesting that these mechanism are central to understanding both structure and function of cortical synaptic wiring. PMID- 26866370 TI - Correction: Live Imaging of Innate Immune Cell Sensing of Transformed Cells in Zebrafish Larvae: Parallels between Tumor Initiation and Wound Inflammation. PMID- 26866371 TI - Integrating Cervical Cancer Screening with HIV Care in Cameroon: Comparative Risk Analysis of Cervical Disease in HIV-Infected Women Receiving Antiretroviral Therapy to Women in the General Population. AB - BACKGROUND: While the effect of highly active antiretroviral therapy (HAART) on natural history of cervical lesions remains controversial, resource limited countries need to understand the relevance of their own data to their settings. We compared the risk of cervical disease in HAART-experienced women with that in women in the general population of Cameroon. METHODS: A retrospective cross sectional survey of women aged 35 years and above, attending a voluntary screening campaign for cervical cancer at the Nkongsamba Regional Hospital in Cameroon between February and May 2014. Squamous intraepithelial lesions (SIL) were determined by Pap smear. Multiple logistic regression was used to compare the odds of SIL in women on HAART to women from the community with unknown HIV status. RESULTS: Included were 302 women of whom 131(43.4%) were HIV-infected and receiving HAART on the site while 171 (56.6%) were women from the community. Cervical disease was observed in 51(16.9%) persons of whom 15 (11.5%) cases in the HAART group and 36 (21.1%) cases in the general group (p = 0.027). After controlling for age and other covariates, women in the HAART group had a 67% reduction in the odds of cervical lesions compared with the community group [adjusted odd ratio (aOR) = 0.33, 95%CI: 0.15-0.73, p = 0.006). CONCLUSION: HIV infected women receiving HAART have a lower risk of cancer than women in the general population. This finding may not be attributed to HAART alone but to all the health benefits derived from receiving a comprehensive HIV care. PMID- 26866372 TI - Mesenchymal Stromal Cells Prevent Renal Fibrosis in a Rat Model of Unilateral Ureteral Obstruction by Suppressing the Renin-Angiotensin System via HuR. AB - We studied Mesenchymal Stromal Cells (MSC) effects in experimental Unilateral Ureteral Obstruction (UUO), a fibrogenic renal disease. Rats were divided in 5 groups: sham, UUO, MSC treated-UUO, ACEi treated-UUO, MSC+ACEi treated- UUO. Data were collected at 1, 7, 21 days. UUO induced monocyte renal infiltration, tubular cell apoptosis, tubular atrophy, interstitial fibrosis and overexpression of TGFbeta, Renin mRNA (RENmRNA), increase of Renin, Angiotensin II (AII) and aldosterone serum levels. Both lisinopril (ACEi) and MSC treatment prevented monocyte infiltration, reduced tubular cell apoptosis, renal fibrosis and TGFbeta expression. Combined therapy provided a further suppression of monocyte infiltration and tubular injury. Lisinopril alone caused a rebound activation of Renin-Angiotensin System (RAS), while MSC suppressed RENmRNA and Renin synthesis and induced a decrease of AII and aldosterone serum levels. Furthermore, in in vitro and in-vivo experiments, MSC inhibit Human antigen R (HuR) trascription, an enhancer of RENmRNA stability by IL10 release. In conclusion, we demonstrate that in UUO MSC prevent fibrosis, by decreasing HuR-dependent RENmRNA stability. Our findings give a clue to understand the molecular mechanism through which MSC may prevent fibrosis in a wide and heterogeneous number of diseases that share RAS activation as common upstream pathogenic mechanism. PMID- 26866373 TI - Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways. AB - Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1beta), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1beta. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation. PMID- 26866374 TI - Staphylococcus aureus Nasal Carriage among Beefpacking Workers in a Midwestern United States Slaughterhouse. AB - Occupational contact with livestock is an established risk factor for exposure to livestock-associated methicillin-resistant Staphylococcus aureus (MRSA), particularly among industrial swine workers. While S. aureus is known to infect cattle, livestock-associated S. aureus carriage among workers in the beef production chain has received limited attention. Beefpacking workers, who slaughter, butcher and process cattle, have intensified exposure to potentially infectious animal materials and may be at risk of livestock-associated S. aureus exposure. We conducted a cross-sectional study of beefpacking workers (n = 137) at an industrial slaughterhouse in the Midwestern United States to evaluate prevalence and characteristics of S. aureus nasal colonization, specifically the absence of the scn gene to identify putative association with livestock, antibiotic susceptibility, presence of Panton-Valentin leukocidin (PVL) genes lukS-PV and lukF-PV, and spa type. Overall prevalence of S. aureus nasal carriage was 27.0%. No workers carried livestock-associated MRSA. Methicillin-sensitive S. aureus isolates (MSSA) recovered from five workers (3.6%) lacked the scn gene and were considered putative livestock-associated S. aureus (pLA-SA). Among pLA-SA isolates, spa types t338, t748, t1476 and t2379 were identified. To our knowledge, these spa types have not previously been identified as associated with livestock. Prevalence of human-adapted MRSA carriage in workers was 3.6%. MRSA isolates were identified as spa types t002, t008 and t024, and four of five MRSA isolates were PVL-positive. To date, this is the first study to indicate that industrial beefpacking workers in the United States may be exposed to livestock associated S. aureus, notably MSSA, and to spa types not previously identified in livestock and livestock workers. Occupational exposure to livestock-associated S. aureus in the beef production chain requires further epidemiologic investigation. PMID- 26866376 TI - A stimulus-location effect in contingency-governed, but not rule-based, discrimination learning. AB - We tested pigeons' acquisition of a conditional discrimination task between colored grating stimuli that included choosing 1 of 2 response keys, which either appeared as white keys to the left and right of the discriminative stimulus, or were replicas of the stimulus. Pigeons failed to acquire the discrimination when the response keys were white disks but succeeded when directly responding to a replica of the stimulus. These results highlight how conditioning processes shape learning in pigeons: The results can be accounted for by supposing that, when pigeons were allowed to respond directly toward the stimulus, learning was guided by classical conditioning, but that responding to white keys demanded instrumental learning, which impaired task acquisition for pigeons. In contrast, humans completing the same paradigm showed no differential learning success depending on whether figure or position indicated the correct key. However, only participants who could state the underlying discrimination rule acquired the task, which implies that human performance in this situation relied on the deduction and application of task rules instead of associative processes. PMID- 26866377 TI - Seeing through Walls at the Nanoscale: Microwave Microscopy of Enclosed Objects and Processes in Liquids. AB - Noninvasive in situ nanoscale imaging in liquid environments is a current imperative in the analysis of delicate biomedical objects and electrochemical processes at reactive liquid-solid interfaces. Microwaves of a few gigahertz frequencies offer photons with energies of ~10 MUeV, which can affect neither electronic states nor chemical bonds in condensed matter. Here, we describe an implementation of scanning near-field microwave microscopy for imaging in liquids using ultrathin molecular impermeable membranes separating scanning probes from samples enclosed in environmental cells. We imaged a model electroplating reaction as well as individual live cells. Through a side-by-side comparison of the microwave imaging with scanning electron microscopy, we demonstrate the advantage of microwaves for artifact-free imaging. PMID- 26866375 TI - AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation. AB - Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016), arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3) is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10) biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients. PMID- 26866378 TI - Assessment of Bowel Wall Enhancement for the Diagnosis of Intestinal Ischemia in Patients with Small Bowel Obstruction: Value of Adding Unenhanced CT to Contrast enhanced CT. AB - Purpose To determine whether adding unenhanced computed tomography (CT) to contrast material-enhanced CT improves the diagnostic performance of decreased bowel wall enhancement as a sign of ischemia complicating mechanical small bowel obstruction (SBO). Materials and Methods This retrospective study was approved by the institutional review board, which waived the requirement for informed consent. Two gastrointestinal radiologists independently performed retrospective assessments of 164 unenhanced and contrast-enhanced CT studies from 158 consecutive patients (mean age, 71.2 years) with mechanical SBO. The reference standard was the intraoperative and/or histologic diagnosis (in 80 cases) or results from clinical follow-up in patients who did not undergo surgery (84 cases). Decreased bowel wall enhancement was evaluated with contrast-enhanced images then and both unenhanced and contrast-enhanced images 1 month later. Diagnostic performance of decreased bowel wall enhancement and confidence in the diagnosis were compared between the two readings by using McNemar and Wilcoxon signed rank tests. Interobserver agreement was assessed by using kappa statistics and compared with bootstrapping. Results Ischemia was diagnosed in 41 of 164 (25%) episodes of SBO. For both observers, adding unenhanced images improved decreased bowel wall enhancement sensitivity (observer 1: 46.3% [19 of 41] vs 65.8% [27 of 41], P = .02; observer 2: 56.1% [23 of 41] vs 63.4% [26 of 41], P = .45), Youden index (from 0.41 to 0.58 for observer 1 and from 0.42 to 0.61 for observer 2), and confidence score (P < .001 for both). Specificity significantly increased for observer 2 (84.5% [104 of 123] vs 94.3% [116 of 123], P = .002), and interobserver agreement significantly increased, from moderate (kappa = 0.48) to excellent (kappa = 0.89; P < .0001). Conclusion Adding unenhanced CT to contrast-enhanced CT improved the sensitivity, diagnostic confidence, and interobserver agreement of the diagnosis of ischemia, a complication of mechanical SBO, on the basis of decreased bowel wall enhancement. ((c)) RSNA, 2016. PMID- 26866381 TI - A Single-Nucleotide Polymorphism of miR-196a2T>C rs11614913 Is Associated with Hepatocellular Carcinoma in the Chinese Population. AB - OBJECTIVE: We investigated the miR-196a2T>C rs11614913 variant in the initiation and progression of hepatocellular carcinoma (HCC). METHODS: A case-control research model was conducted and the genotypes of 109 HCC patients and 105 healthy controls were identified by direct sequencing. The correlation between the rs11614913 genotypes and the susceptibility to HCC was evaluated using an unconditional logistic regression model. RESULTS: We found that 20/109 (18.3%) patients were TT homozygote, whereas 64/109 (58.8%) patients had the CT genotype, and 25/109 (22.9%) patients had the CC genotype. In control samples, the frequency of the TT homozygote was 33.3%, that of CT was 49.5%, and that of CC was 17.1%. After adjusting for age and gender by logistic regression analysis, we found significant differences in susceptibility to HCC by genotype (TT vs. CT+CC: OR = 2.52, 95%CI = 1.18-4.19; p < 0.05). The CT and CC genotypes were more common in HCC patients compared to controls. Moreover, the CT+CC genotypes were associated with a poor HCC prognosis. CONCLUSIONS: In this study, we found that the CT+CC genotypes of rs11614913 were significantly associated with an increased risk and poor prognosis for HCC in the Chinese population. PMID- 26866382 TI - Polymer-lipid hybrid systems: merging the benefits of polymeric and lipid-based nanocarriers to improve oral drug delivery. AB - INTRODUCTION: A number of biobarriers limit efficient oral drug absorption; both polymer-based and lipid-based nanocarriers have demonstrated properties and delivery mechanisms to overcome these biobarriers in preclinical settings. Moreover, in order to address the multifaceted oral drug delivery challenges, polymer-lipid hybrid systems are now being designed to merge the beneficial features of both polymeric and lipid-based nanocarriers. AREAS COVERED: Recent advances in the development of polymer-lipid hybrids with a specific focus on their viability in oral delivery are reviewed. Three classes of polymer-lipid hybrids have been identified, i.e. lipid-core polymer-shell systems, polymer-core lipid-shell systems, and matrix-type polymer-lipid hybrids. We focus on their application to overcome the various biological barriers to oral drug absorption, as exemplified by selected preclinical studies. EXPERT OPINION: Numerous studies have demonstrated the superiority of polymer-lipid hybrid systems to their non hybrid counterparts in providing improved drug encapsulation, modulated drug release, and improved cellular uptake. These features have encouraged their applications in the delivery of chemotherapeutics, proteins, peptides, and vaccines. With further research expected to optimize the manufacturing and scaling up processes and in-depth pre-clinical pharmacological and toxicological assessments, these multifaceted drug delivery systems will have significant clinical impact on the oral delivery of pharmaceuticals and biopharmaceuticals. PMID- 26866383 TI - Antidiabetic activity of Helicteres angustifolia root. AB - Context The root of Helicteres angustifolia L. (Sterculiaceae) has been used as folk herbal drug to treat cancer, bacterial infections, inflammatory, and flu in China. However, there is no report on its antidiabetic activity. Objective This study evaluates the antidiabetic activity of ethanol extract from H. angustifolia root. Materials and methods The promoting effect of H. angustifolia root ethanol extract (25, 50, and 100 MUg/mL) on glucose uptake was evaluated using HepG2 cell, differentiated C2C12 myotubes, and differentiated 3T3-L1 adipocytes. The antidiabetic activity of the extract was assessed in vivo using STZ-induced diabetic rats by orally administration of the extract (200 and 400 mg/kg b.w.) once per day for 28 d. Blood glucose, TG, TC, TP, HDL-C, UA, BUN, AST, ALT, insulin, and HOMA-IR were analyzed. Results The results showed that the extract increased glucose uptake in C2C12 myotubes and 3T3-L1 adipocytes with an IC50 value of 79.95 and 135.96 MUg/mL, respectively. And about 12%, 19%, and 10% (p < 0.05) in HepG2 cells when compared with the control at the concentration of 25, 50, and 100 MUg/mL, respectively. After 28 days' treatment with the extract, significant reduction was observed in blood glucose, HOMA-IR, TC, TG, UA, BUN, AST, and ALT levels, while the levels of TP and HDL cholesterol increased. Discussion and conclusion These results suggest that H. angustifolia root ethanol extract possess potent antidiabetic activity, which is the first report on antidiabetic activity of this plant. PMID- 26866384 TI - Environmentally Friendly Mechanochemical Syntheses and Conversions of Highly Luminescent Cu(I) Dinuclear Complexes. AB - Luminescent dinuclear Cu(I) complexes, [Cu2X2(dpypp)2] [Cu-X; X = Cl, Br, I; dpypp = 2,2'-(phenylphosphinediyl)dipyridine], were successfully synthesized by a solvent-assisted mechanochemical method. A trace amount of the assisting solvent plays a key role in the mechanochemical synthesis; only two solvents possessing the nitrile group, CH3CN and PhCN, were effective for promoting the formation of dinuclear Cu-X. X-ray analysis revealed that the dinuclear structure with no Cu...Cu interactions, bridged by two dpypp ligands, was commonly formed in all Cu X species. These complexes exhibited bright green emission in the solid state at room temperature (Phi = 0.23, 0.50, and 0.74; lambdaem = 528, 518, and 530 nm for Cu-Cl, Cu-Br, and Cu-I, respectively). Emission decay measurement and TD-DFT calculation suggested that the luminescence of Cu-X could be assigned to phosphorescence from the triplet metal-to-ligand charge-transfer ((3)MLCT) excited state, effectively mixed with the halide-to-ligand charge-transfer ((3)XLCT) excited state, at 77 K. The source of emission changed to thermally activated delayed fluorescence (TADF) with the same electronic transition nature at room temperature. In addition, the CH3CN-bound analogue, [Cu2(CH3CN)2(dpypp)2](BF4)2, was successfully mechanochemically converted to Cu-X by grinding with solid KX in the presence of a trace amount of assisting water. PMID- 26866385 TI - Dense Poly(ethylene glycol) Brushes Reduce Adsorption and Stabilize the Unfolded Conformation of Fibronectin. AB - Polymer brushes, in which polymers are end-tethered densely to a grafting surface, are commonly proposed for use as stealth coatings for various biomaterials. However, although their use has received considerable attention, a mechanistic understanding of the impact of brush properties on protein adsorption and unfolding remains elusive. We investigated the effect of the grafting density of poly(ethylene glycol) (PEG) brushes on the interactions of the brush with fibronectin (FN) using high-throughput single-molecule tracking methods, which directly measure protein adsorption and unfolding within the brush. We observed that, as grafting density increased, the rate of FN adsorption decreased; however, surface-adsorbed FN unfolded more readily, and unfolded molecules were retained on the surface for longer residence times relative to those of folded molecules. These results, which are critical for the rational design of PEG brushes, suggest that there is a critical balance between protein adsorption and conformation that underlies the utility of such brushes in physiological environments. PMID- 26866386 TI - The Dynamic Landscape of the Full-Length HIV-1 Transactivator of Transcription. AB - The type 1 human immunodeficiency virus (HIV-1) transactivator of transcription (Tat) is a small RNA-binding protein essential for viral gene expression and replication. It has also been shown to bind to a large number of human proteins and to modulate many different cellular activities. We have used nuclear magnetic resonance (NMR) spectroscopy and hydrogen exchange chemistry to measure backbone dynamics over the millisecond to picosecond time scales. Sequential backbone assignment was facilitated by several isotope labeling schemes, including uniform labeling, site-specific labeling, and unlabeling. (15)N NMR relaxation parameters were measured and analyzed by reduced spectral density mapping and the Lipari Szabo Model-Free approach to characterize the backbone dynamics on the picosecond to nanosecond time scale. The results indicate that the protein exists in an extended disordered conformational ensemble. NMR relaxation dispersion profiles show that on the millisecond time scale no conformational exchange is detected for any of the residues, supporting the model of a disordered backbone. NMR chemical shift differences from random coil values suggest that some segments of the protein have a modest propensity to fold; comparison to X-ray diffraction structures of Tat complexes indicates that some segments of the protein function through an induced-fit mechanism whereas other segments likely operate by conformational selection. Surprisingly, measured hydrogen exchange rates are higher than predicted for a disordered polymer, but this is explained as being caused by the high net charge on the protein that enhances base-catalyzed hydrogen exchange. The dynamics results provide a deeper understanding of the protein conformational ensemble and form a foundation for future studies of the conformational changes that accompany the formation of the superelongation complex that activates viral transcription. PMID- 26866388 TI - Inverted Quantum-Dot Light-Emitting Diodes Fabricated by All-Solution Processing. AB - All-solution processed, multilayer, and inverted quantum-dot light-emitting diodes (QD-LEDs) are developed in this work. To protect the QDs from dissolving by the solvents of upper layers, the solvents of poly(9-vinlycarbazole) (PVK) hole transporting layer are first investigated. The QD layer has been less affected by o-dichlorobenzene solvent than other typical solvents like chloroform and chlorobenzene. Second, to deposit a hydrophilic poly(ethylenedioxythiophene)/polystyrenesulfonate ( PEDOT: PSS) hole injection layer on top of hydrophobic PVK, the surface energy of the PEDOT: PSS is reduced by using isopropanol as the additive. With optimized conditions, the demonstrated QD-LEDs exhibit a maximum luminance of 16290 cd/m(2) and a peak current efficiency of 4.1 cd/A, which is the highest among the reported values. These results may offer a practicable platform for further research, leading to the achievement of all-solution processed, multilayer, and efficient inverted QD LEDs. PMID- 26866387 TI - Meeting the Needs for Released Nanomaterials Required for Further Testing-The SUN Approach. AB - The analysis of the potential risks of engineered nanomaterials (ENM) has so far been almost exclusively focused on the pristine, as-produced particles. However, when considering a life-cycle perspective, it is clear that ENM released from genuine products during manufacturing, use, and disposal is far more relevant. Research on the release of materials from nanoproducts is growing and the next necessary step is to investigate the behavior and effects of these released materials in the environment and on humans. Therefore, sufficient amounts of released materials need to be available for further testing. In addition, ENM free reference materials are needed since many processes not only release ENM but also nanosized fragments from the ENM-containing matrix that may interfere with further tests. The SUN consortium (Project on "Sustainable Nanotechnologies", EU seventh Framework funding) uses methods to characterize and quantify nanomaterials released from composite samples that are exposed to environmental stressors. Here we describe an approach to provide materials in hundreds of gram quantities mimicking actual released materials from coatings and polymer nanocomposites by producing what is called "fragmented products" (FP). These FP can further be exposed to environmental conditions (e.g., humidity, light) to produce "weathered fragmented products" (WFP) or can be subjected to a further size fractionation to isolate "sieved fragmented products" (SFP) that are representative for inhalation studies. In this perspective we describe the approach, and the used methods to obtain released materials in amounts large enough to be suitable for further fate and (eco)toxicity testing. We present a case study (nanoparticulate organic pigment in polypropylene) to show exemplarily the procedures used to produce the FP. We present some characterization data of the FP and discuss critically the further potential and the usefulness of the approach we developed. PMID- 26866389 TI - Isomerization Pathways of ONCNO: Unstable or Metastable? AB - Fulminates containing the CNO(-) ion have been widely utilized as high-energy density materials (HEDMs) for more than 120 years. Yet no purely covalently bound CNO molecule, i.e., nitrile oxide, is known to behave as an HEDM. In this study, we performed a thorough investigation of the potential energy surface of nitrile oxide ONCNO and related isomers, applying various sophisticated methods including G4, CBS-QB3, W1BD, CCSD(T)/CBS, and CASPT2/CBS. The Gibbs free energy calculations showed that the decomposition of ONCNO to the considerably endothermic products CNO + NO is favored compared to that into the highly exothermic products CO2 + N2. Thus, ONCNO fails to be the long expected nitrile oxide HEDM. However, with the rate-determining barrier of 23.3 kcal mol(-1) at the W1BD level, ONCNO should be experimentally accessible. PMID- 26866391 TI - Oxidation of Tetraphenylhexaazaanthracene: Accessing a Scissor Dimer of a 16pi Biscyanine. AB - Tetraphenylhexaazaanthracene (TPHA), a fluorescent zwitterionic biscyanine with a closed-shell singlet ground state, on treatment with manganese dioxide or phenyliodine bis(trifluoroacetate) (PIFA), undergoes oxidative dimerization to give a near-zero dipole scissor 5,5'-dimer DI-TPHA. Both acene components of the new dimer DI-TPHA maintain their biscyanine closed-shell singlet ground state motifs, as judged by analysis of both single crystal X-ray crystallographic and density functional theory computational studies; however, unlike TPHA, DI-TPHA is only very weakly fluorescent. PMID- 26866390 TI - Serial Femtosecond Crystallography and Ultrafast Absorption Spectroscopy of the Photoswitchable Fluorescent Protein IrisFP. AB - Reversibly photoswitchable fluorescent proteins find growing applications in cell biology, yet mechanistic details, in particular on the ultrafast photochemical time scale, remain unknown. We employed time-resolved pump-probe absorption spectroscopy on the reversibly photoswitchable fluorescent protein IrisFP in solution to study photoswitching from the nonfluorescent (off) to the fluorescent (on) state. Evidence is provided for the existence of several intermediate states on the pico- and microsecond time scales that are attributed to chromophore isomerization and proton transfer, respectively. Kinetic modeling favors a sequential mechanism with the existence of two excited state intermediates with lifetimes of 2 and 15 ps, the second of which controls the photoswitching quantum yield. In order to support that IrisFP is suited for time-resolved experiments aiming at a structural characterization of these ps intermediates, we used serial femtosecond crystallography at an X-ray free electron laser and solved the structure of IrisFP in its on state. Sample consumption was minimized by embedding crystals in mineral grease, in which they remain photoswitchable. Our spectroscopic and structural results pave the way for time-resolved serial femtosecond crystallography aiming at characterizing the structure of ultrafast intermediates in reversibly photoswitchable fluorescent proteins. PMID- 26866393 TI - Novel Tools, Biomarkers, and Disease Entities in Esophageal Disorders. PMID- 26866392 TI - The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments. AB - OBJECTIVES: Bowel preparations (BPs) taken before colonoscopy may introduce a confounding effect on the results of gastrointestinal microbiota studies. This study aimed to determine the effect of bowel preparation on the mucosa-associated and luminal colonic microbiota in healthy subjects (HC) and inflammatory bowel disease (IBD) patients. METHODS: Biopsy samples (n=36) and fecal samples (n=30) were collected from 10 HC and 8 IBD subjects pre- and post-BP. 16S rRNA gene was pyrosequenced using 454 Titanium protocols. We compared the differences between the pre- and post-BP samples (i.e., comparisons-across-bowel-prep); we examined the effect of BP on the expected separation of the mucosal vs. the luminal compartments (i.e., comparisons-across-compartments). Last, we compared the baseline differences between the HC vs. IBD groups (a secondary analysis), and examined whether the differences between the HC vs. IBD changed after BP. RESULTS: In comparisons-across-bowel-prep, the Shannon's index (SI) decreased only in the biopsy samples of IBD subjects post-BP (P=0.025) and phylogenetic diversity-whole tree (PD-WT) metric decreased in biopsy samples of HC subjects post-BP (P=0.021). In secondary comparisons, the subtle differences between the fecal samples of the HC vs. IBD groups, in terms of evenness and the SI, were not apparent post-BP. In terms of beta-diversity, in comparisons-across-bowel-prep, the proportion of shared operational taxonomic units (OTUs) in pre- and post-BP samples was low (~30%) and unweighted Unifrac distances between pre- and post-BP specimens ranged from 0.52 to 0.66. HC biopsies were affected more than IBD biopsies with BP (P=0.004). In comparisons-across-compartments, the proportion of shared OTUs between biopsy and fecal samples increased and Unifrac distances decreased post-BP in IBD subjects, reducing the differences between the mucosal and luminal compartments of the gut microbiota. Interindividual differences in Unifrac distances were preserved even with BP effects, although the effects were greater on weighted Unifrac distances. Bacteroidetes and its subtypes increased post-BP in both the luminal and mucosal compartments. CONCLUSIONS: Bowel preparations affect the composition and diversity of the fecal and luminal microbiota in the short term, introducing potential bias into experiments examining the gut microbiota. The magnitude of the effect of BP is not greater than that of interindividual variation. Both the luminal and mucosal compartments of the gut microbiota get affected, and samples from controls and IBD subjects may get affected differently. Studies of the colonic microbiota should take into account the direction and the magnitude of the change introduced by BP during the design stage of the experiments, and consider sample sizes so that potential bias is minimized. PMID- 26866394 TI - A self-assembly aptasensor based on thick-shell quantum dots for sensing of ochratoxin A. AB - A novel self-assembling aptasensor was fabricated by precisely attaching three phosphorothioate-modified capture aptamers onto a single thick-shell quantum dot in a controllable manner for monitoring of ochratoxin A (OTA), a poisonous contaminant widespread in foodstuffs. Herein, CdSe/CdS QDs coated in ten layer CdS shells were synthesized using a continual precursor injection method. Analysis of the prepared CdSe/CdS QDs showed a zinc-blende structure, high photoluminescence quantum yields (>80%), and a photoemission peak with a narrow full-width at half-maximum (about 29 nm), all qualities that render them as a superior choice for optical applications. By adjusting the number of phosphorothioate bases in the anchor domain, the tunable-valency aptasensor was able to self-assemble. In the sensing strategy, the thick-shell quantum dot was provided as an acceptor while OTA itself was used as a donor. In the presence of OTA, the capture aptamers drive the aptasensor function into a measurable signal through a fluorescence resonance energy transfer (FRET) system. The newly developed aptasensor had a detection limit as low as 0.5 ng mL(-1), with a linear concentration in the range of 1 to 30 ng mL(-1), and therefore meets the requirements for rapid, effective, and anti-interference sensors for real-world applications. Moreover, the high quality thick-shell QDs provide an ideal alternative for highly sensitive imaging and intensive illumination in the fields of biotechnology and bioengineering. PMID- 26866395 TI - Senior Tech: The Next Generation: Health Informatics Solutions for Older Adults Living in the Community. PMID- 26866400 TI - How to Put Individuals at the Heart of Health Care: AGS Advances Definition of Person-Centered Care. PMID- 26866398 TI - Optimizing Medication Use Through Deprescribing: Tactics for This Approach. AB - As older adults age, it is imperative to constantly reevaluate medications. Deprescribing, the process of identifying and discontinuing drugs that could potentially harm rather than benefit a patient, should therefore be considered in all older adults on an individual basis. Nurses are a critical part of the team in addressing this issue. The current article discusses deprescribing, tactics to this approach, and important areas for future development. PMID- 26866401 TI - Ir(III)-catalyzed C-H alkynylation of arenes under chelation assistance. AB - An efficient and mild Ir(III)-catalyzed, chelation assisted C-H alkynylation of arenes has been developed using hypervalent iodine alkynes as alkynylating reagents. A broad scope of N-phenyl-2-aminopyridines and 2-phenoxypyridines has been established as effective substrates for this C-H functionalization and the desired alkynylated products were isolated in moderate to high yields. PMID- 26866402 TI - Interaction of europium and curium with alpha-amylase. AB - The complexation of Eu(iii) and Cm(iii) with the protein alpha-amylase (Amy), a major enzyme in saliva and pancreatic juice, was investigated over wide ranges of pH and concentration at both ambient and physiological temperatures. Macroscopic sorption experiments demonstrated a strong and fast binding of Eu(iii) to Amy between pH 5 and 8. The protein provides three independent, non-cooperative binding sites for Eu(iii). The overall association constant of these three binding sites on the protein was calculated to be log K = 6.4 +/- 0.1 at ambient temperature. With potentiometric titration, the averaged deprotonation constant of the carboxyl groups (the aspartic and glutamic acid residues) of Amy was determined to be pKa = 5.23 +/- 0.14 at 25 degrees C and 5.11 +/- 0.24 at 37 degrees C. Time-resolved laser-induced fluorescence spectroscopy (TRLFS) revealed two different species for both Eu(iii) and Cm(iii) with Amy. In the case of the Eu(iii) species, the stability constants were determined to be log beta11 = 4.7 +/- 0.2 and log beta13 = 12.0 +/- 0.4 for Eu : Amy = 1 : 1 and 1 : 3 complexes, respectively, whereas the values for the respective Cm(iii) species were log beta11 = 4.8 +/- 0.1 and log beta13 = 12.1 +/- 0.1. Furthermore, the obtained stability constants were extrapolated to infinite dilution to make our data compatible with the existing thermodynamic database. PMID- 26866403 TI - Metabolomics analysis of exhaled breath condensate for discrimination between lung cancer patients and risk factor individuals. AB - The search for new clinical tests aimed at diagnosing chronic respiratory diseases is a current research line motivated by the lack of efficient screening tools and the severity of some of these pathologies. Alternative biological samples can open the door to new screening tools. A promising biofluid that is rarely used for diagnostic purposes is exhaled breath condensate (EBC), the composition of which has been inadequately studied. In this research, untargeted analysis of EBC using gas chromatography time-of-flight mass spectrometry has been applied to a cohort of patients with lung cancer (n = 48), risk factor individuals (active smokers and ex-smokers, n = 130) and control healthy individuals (non-smokers without respiratory diseases, n = 61). An identical protocol was applied to the two EBC fractions provided by the sampling device (upper and central airways and distal airway) from each individual, which allowed the compositional differences between the two EBC fractions to be detected. Tentative compounds that contribute to discrimination between the three groups were identified, and a relevant role for lipids such as monoacylglycerols and squalene was found. These results could support the ability of metabolomics to go inside the study of lung cancer. PMID- 26866404 TI - Promoting a Culture of Safety. PMID- 26866405 TI - Evaluation of 2-Stage Injection Technique in Children. AB - Effective pain control during local anesthetic injection is the cornerstone of behavior guidance in pediatric dentistry. The aim of this study was to evaluate the practical efficacy of a 2-stage injection technique in reducing injection pain in children. This was a split-mouth, randomized controlled crossover trial. One hundred cooperative children aged 7 to 13 years in need of bilateral local anesthetic injections (inferior alveolar nerve block, posterior superior alveolar nerve block, or maxillary and mandibular buccal infiltrations) for restorative, endodontic, and extraction treatments were recruited for the study. Children were randomly allocated to receive either the 2-stage injection technique or conventional technique at the first appointment. The other technique was used at the successive visit after 1 week. Subjective and objective evaluation of pain was done using the Wong-Baker FACES Pain Rating Scale (FPS) and Sound Eye Motor (SEM) scale, respectively. The comparison of pain scores was done by Wilcoxon sign-rank test. Both FPS and SEM scores were significantly lower when the 2-stage injection technique of local anesthetic nerve block/infiltration was used compared with the conventional technique. The 2-stage injection technique is a simple and effective means of reducing injection pain in children. PMID- 26866406 TI - Dentists' and Parents' Attitude Toward Nitrous Oxide Use in Kuwait. AB - The aim of this study was to investigate the attitude of dentists in Kuwait toward the use of nitrous oxide sedation as a behavior management technique (BMT) for pediatric patients and assess their training in nitrous oxide sedation. In addition, we assessed parents' knowledge of and attitude toward the use of nitrous oxide as a BMT for their children. The objective was to determine if nitrous oxide sedation is being provided and utilized as a means to enhance dental care for pediatric patients. A cross-sectional survey was randomly distributed to both groups of interest: parents accompanying their children to the dentist and licensed dentists in Kuwait. Participants had to meet certain inclusion criteria to be included in the survey and had to complete the entire questionnaire to be part of the analysis. A total of 381 parents completed the questionnaires. The majority of parents responded that they were unaware of nitrous oxide sedation and were not aware of it as a BMT (79%). Two thirds of the parent would accept nitrous oxide sedation if recommended by a dentist treating their children. Two hundred and one dentists completed the survey and met the inclusion criteria. The majority (74.5%) of dentists were willing to use nitrous oxide as a BMT. However, only 6% were utilizing nitrous oxide sedation and providing it to their child patient if indicated. The main reasons for this huge gap are lack of facilities/equipment and lack of training as indicated by the dentists. This study showed that parents are accepting nitrous oxide sedation as a BMT for their children. It also showed the willingness of the dentists to provide such BMT to their patients. The lack of training and lack of equipment are the main barriers to providing such service to the patients. More training courses and more facilities should be provided to eliminate such barriers. PMID- 26866407 TI - Lidocaine Concentration in Oral Tissue by the Addition of Epinephrine. AB - The vasoconstrictive effect due to the addition of epinephrine to local anesthetic has been clearly shown by measuring blood-flow volume or blood anesthetic concentration in oral mucosal tissue. However, there are no reports on the measurement of anesthetic concentration using samples directly taken from the jawbone and oral mucosal tissue. Consequently, in this study, the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine was considered by quantitatively measuring lidocaine concentration within the tissue. Japanese white male rabbits (n = 96) were used as test animals. General anesthesia was induced by sevoflurane and oxygen, and then cannulation to the femoral artery was performed while arterial pressure was constantly recorded. Infiltration anesthesia was achieved by 0.5 mL of 2% lidocaine containing 1 : 80,000 epinephrine in the upper jawbone (E(+)) and 0.5 mL of 2% of epinephrine additive-free lidocaine (E(0)) under the periosteum. At specified time increments (10, 20, 30, 40, 50, and 60 minutes), samples from the jawbone, oral mucosa, and blood were collected, and lidocaine concentration was directly measured by high-performance liquid chromatography. No significant differences in the change in blood pressure were observed either in E(+) or E(0). In both E(+) and E(0) groups, the serum lidocaine concentration peaked 10 minutes after local anesthesia and decreased thereafter. At all time increments, serum lidocaine concentration in E(+) was significantly lower than that in E(0). There were no significant differences in measured lidocaine concentration between jawbone and mucosa within either the E(+) or the E(0) groups at all time points, although the E(0) group had significantly lower jawbone and mucosa concentrations than the E(+) group at all time points when comparing the 2 groups to each other. Addition of epinephrine to the local anesthetic inhibited systemic absorption of local anesthetic into the blood such that a high concentration could be maintained in the tissue. Epinephrine-induced vasoconstrictive effect was observed not only in the oral mucosa but also in the jawbone. PMID- 26866408 TI - Tetany During Intravenous Conscious Sedation in Dentistry Resulting From Hyperventilation-Induced Hypocapnia. AB - Hyperventilation can be a manifestation of anxiety that involves abnormally fast breathing (tachypnea) and an elevated minute ventilation that exceeds metabolic demand. This report describes a case of hyperventilation-induced hypocapnia resulting in tetany in a 16-year-old girl undergoing orthodontic extractions under intravenous conscious sedation. Pulse oximetry is the gold standard respiratory-related index in conscious sedation. Although the parameter has great utility in determining oxygen desaturation, it provides no additional information on respiratory function, including, for example, respiratory rate. In this case, we found capnography to be a very useful aid to monitor respiration in this patient and also to treat the hypocapnia. PMID- 26866409 TI - Anesthetic Management of a Patient With Takayasu Arteritis. AB - Takayasu arteritis is a rare chronic progressive panendarteritis involving the aorta and its main branches. Anesthesia in patients with this disease can be complicated by severe uncontrolled hypertension, end-organ dysfunction, and stenosis of major blood vessels. In this case, general anesthesia was induced with sevoflurane and remifentanil without complications. To prevent intraoperative complications, we conducted intubation with a rigid video laryngoscope with careful consideration of the concentrations of analgesics and sedatives used. This case demonstrates the importance of anesthetic techniques for maintaining adequate tissue perfusion without hemodynamic changes in the anesthetic management of patients with Takayasu arteritis. PMID- 26866410 TI - Cardiovascular Collapse Associated With Irreversible Cardiomyopathy, Chronic Renal Failure, and Hypertension During Routine Dental Care. AB - Patients with multiple comorbid conditions visit the dental office every day, and although rare, complications from their conditions may occur during treatment. A case is presented of a 65-year-old African American woman with a history of severe cardiovascular disease, renal disease, and a reported local anesthetic allergy who experienced complete cardiovascular collapse during routine dental treatment from which she was successfully resuscitated. Treating clinicians should recognize the emerging symptoms and be proficient with a basic and advanced cardiac life support protocol to care for their patients safely and effectively until they can be transported to more advanced care facilities. PMID- 26866411 TI - Potent Inhalational Anesthetics for Dentistry. AB - Nitrous oxide and the volatile inhalational anesthetics have defined anxiety and pain control in both dentistry and medicine for over a century. From curious experimentation to spectacular public demonstrations, the initial work of 2 dentists, Horace Wells and William T. G. Morton, persists to this day in modern surgery and anesthesia. This article reviews the history, similarities, differences, and clinical applications of the most popular inhalational agents used in contemporary dental surgical settings. PMID- 26866412 TI - Does social support buffer the effects of occupational stress on sleep quality among paramedics? A daily diary study. AB - Given evidence suggesting a detrimental effect of occupational stress on sleep, it is important to identify protective factors that may ameliorate this effect. We followed 87 paramedics upon waking and after work over 1 week using a daily diary methodology. Multilevel modeling was used to examine whether the detrimental effects of daily occupational stress on sleep quality were buffered by perceived social support availability. Paramedics who reported more support availability tended to report better quality sleep over the week. Additionally, perceived support availability buffered postworkday sleep from average occupational stress and days of especially high occupational stress. Perceived support availability also buffered off-workday sleep from the cumulative amount of occupational stress experienced over the previous workweek. Those with low levels of support displayed poor sleep quality in the face of high occupational stress; those high in support did not show significant effects of occupational stress on sleep. (PsycINFO Database Record PMID- 26866413 TI - Progress Toward Strengthening National Blood Transfusion Services - 14 Countries, 2011-2014. AB - Blood transfusion is a life-saving medical intervention; however, challenges to the recruitment of voluntary, unpaid or otherwise nonremunerated whole blood donors and insufficient funding of national blood services and programs have created obstacles to collecting adequate supplies of safe blood in developing countries (1). Since 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has provided approximately $437 million in bilateral financial support to strengthen national blood transfusion services in 14 countries in sub-Saharan Africa and the Caribbean* that have high prevalence rates of human immunodeficiency virus (HIV) infections. CDC analyzed routinely collected surveillance data on annual blood collections and HIV prevalence among donated blood units for 2011-2014. This report updates previous CDC reports (2,3) on progress made by these 14 PEPFAR-supported countries in blood safety, summarizes challenges facing countries as they strive to meet World Health Organization (WHO) targets, and documents progress toward achieving the WHO target of 100% voluntary, nonremunerated blood donors by 2020 (4). During 2011-2014, overall blood collections among the 14 countries increased by 19%; countries with 100% voluntary, nonremunerated blood donations remained stable at eight, and, despite high national HIV prevalence rates, 12 of 14 countries reported an overall decrease in donated blood units that tested positive for HIV. Achieving safe and adequate national blood supplies remains a public health priority for WHO and countries worldwide. Continued success in improving blood safety and achieving WHO targets for blood quality and adequacy will depend on national government commitments to national blood transfusion services or blood programs through increased public financing and diversified funding mechanisms for transfusion related activities. PMID- 26866414 TI - Fertility and Pregnancy in Primary Adrenal Insufficiency in Germany. AB - Autoimmune adrenalitis (AA) and congenital adrenal hyperplasia (CAH) are the most common reasons for acquired and monogenetic primary adrenal insufficiency. Both concern women in their fertile years. The aim of the work was to examine fertility rates, pregnancy outcome, and children's characteristics in AA and CAH patients in 2 German endocrine centers. One hundred and fifty-eight women were contacted. Thirty-nine patients with CAH due to 21-hydroxlase deficiency and 54 AA patients agreed and were included. Information about course and outcome of pregnancies was obtained by questionnaire and telephone interview. Fertility rates were calculated and compared to expected values from the German general population. Twelve CAH patients (30.8%) had 25 pregnancies, which resulted in 16 children. In AA patients, 93 pregnancies in 42 women (75%) were reported resulting in 73 childbirths. Fertility rates were normal in nonclassic CAH and in AA-only patients, but significantly reduced in classic CAH and autoimmune polyendocrine syndrome type 2 (APS-2). Rates of miscarriages were high in all CAH (36%) and APS-2 (22%) patients. The majority of children in both groups were born at term, but rates of cesarean section were elevated in classic CAH and in AA patients<5 years before or after diagnosis. Children born to CAH patients weighed significantly less than expected and 33.3% of them were born small for gestational age. Fertility seems not to be reduced in general, but specific in classic CAH and APS 2 patients. Nevertheless all CAH and AA patients seem to be at risk of miscarriages and cesarean section. PMID- 26866415 TI - Modified silver nanowire transparent electrodes with exceptional stability against oxidation. AB - We report an easy method to prepare thin, flexible and transparent electrodes that show enhanced inertness toward oxidation using modified silver nanowires (Ag NWs). Stabilization is achieved through the adsorption of triphenylphosphine (PPh3) onto the Ag NW hybrid dispersions prior to their 2D organization as transparent electrodes on polyethylene terephtalate (PET) films. After 110 days in air (20 degrees C) under atmospheric conditions, the transmittance of the PET/Ag NW/PPh3 based films is nearly unchanged, while the transmittance of the PET/Ag NW-based films decreases by about 5%. The sheet resistance increases for both materials as time elapses, but the rate of increase is more than four times slower for films stabilized by PPh3. The improved transmittance and conductivity results in a significantly enhanced stability for the figure of merit sigma dc/sigma op. This phenomenon is highlighted in highly oxidative nitric acid vapor. The tested stabilized films in such conditions exhibit a decrease to sigma dc/sigma op of only 38% after 75 min, whereas conventional materials exhibit a relative loss of 71%. In addition, by contrast to other classes of stabilizers, such as polymer or graphene-based encapsulants, PPh3 does not alter the transparency or conductivity of the modified films. While the present films are made by membrane filtration, the stabilization method could be implemented directly in other liquid processes, including industrially scalable ones. PMID- 26866416 TI - Editorial: Survive to Fight: Effector Treg Cells in Systemic Lupus Erythematosus. PMID- 26866417 TI - Prevalence and Determinants of Fatigue Following Total Knee Replacement: A Longitudinal Cohort Study. AB - OBJECTIVE: To evaluate the prevalence and determinants of clinically important fatigue before and up to 12 months after total knee replacement (TKR) surgery. METHODS: This study was a secondary analysis of a prospective cohort study conducted among 422 patients (ages 45-74 years) undergoing primary TKR for osteoarthritis (OA) who participated in the Maximum Recovery After Knee Replacement randomized clinical trial. Assessments were carried out before, and at 6 weeks, 6 months, and 12 months after surgery. Self-reported fatigue was assessed on a 10-cm visual analog scale. Patients also completed a number of questionnaires evaluating knee pain, activity limitations, psychological well being, comorbidity, and physical activity. Linear regression analyses were conducted to explore 6- and 12-month cross-sectional and longitudinal associations with self-reported fatigue. RESULTS: Clinically important fatigue (>=6.7 of 10) was reported by 145 patients (34%) before surgery, decreasing to 14%, 12%, and 8% at 6 weeks, 6 months, and 12 months after surgery, respectively. In multivariate analyses, muscle strength was strongly associated with fatigue at 6 months, and knee pain, activity limitations, number of comorbidities, and lack of energy were strongly associated with fatigue at both 6 and 12 months after TKR surgery. Female sex, number of comorbidities, depression, and fatigue were all early predictors of fatigue 12 months after TKR. CONCLUSION: Among patients undergoing TKR for OA, clinically important fatigue is considerably prevalent both before and for at least 6 months after surgery. Identifying and addressing early predictors of ongoing fatigue has the potential to improve the quality of life following TKR surgery. PMID- 26866418 TI - New use for an old reagent: Cell cycle analysis of DNA content using flow cytometry in formamide treated cells. AB - Formamide has long been one of the most widely used reagents in the study of nucleic acids. However, the use of formamide for treating cells to be analyzed by flow cytometry is a recent development and is restricted to measuring telomere lengths by flow-FISH. In this field, we have published several papers in order to observe the effects of formamide treatment on cells at room temperature. We therefore discovered that, with suitable modifications, a short and simple incubation in this ionizing solvent facilitates cell cycle analysis by flow cytometry, equivalent or superior to that obtained with treatments in alcohol, acetone or detergent in hypotonic solution. Even using a bulky and problematic stain (low quantum efficiency and G-C base preference), such as 7 aminoactinomycin D (7-AAD) which, on the other hand, has the advantage of being excited at 488 nm and does not bind to the RNA, it is possible to obtain excellent coefficients of variation and (G2-M) mode/(G0-G1) mode ratios. These parameters, especially if stained cells are washed before acquisition, arrive at optimal values. It is noteworthy that the ability to wash the cells stained for DNA content analysis without affecting the stoichiometry of the staining has not been described elsewhere in the literature. With formamide treatment the doublets are practically absent, sample recovery is efficient, as well as the preservation of physical parameters, and the stained cells can be stored for at least 10 days at room temperature before acquisition. (c) 2016 International Society for Advancement of Cytometry. PMID- 26866419 TI - Concise Review: Primary Cilia: Control Centers for Stem Cell Lineage Specification and Potential Targets for Cell-Based Therapies. AB - Directing stem cell lineage commitment prevails as the holy grail of translational stem cell research, particularly to those interested in the application of mesenchymal stem cells and adipose-derived stem cells in tissue engineering. However, elucidating the mechanisms underlying their phenotypic specification persists as an active area of research. In recent studies, the primary cilium structure has been intimately associated with defining cell phenotype, maintaining stemness, as well as functioning in a chemo, electro, and mechanosensory capacity in progenitor and committed cell types. Many hypothesize that the primary cilium may indeed be another important player in defining and controlling cell phenotype, concomitant with lineage-dictated cytoskeletal dynamics. Many of the studies on the primary cilium have emerged from disparate areas of biological research, and crosstalk amongst these areas of research is just beginning. To date, there has not been a thorough review of how primary cilia fit into the current paradigm of stem cell differentiation and this review aims to summarize the current cilia work in this context. The goal of this review is to highlight the cilium's function and integrate this knowledge into the working knowledge of stem cell biologists and tissue engineers developing regenerative medicine technologies. Stem Cells 2016;34:1445-1454. PMID- 26866420 TI - Paradigm Shift in the Surveillance and Management of Dysplasia in Inflammatory Bowel Disease (West). AB - Patients with long-standing inflammatory bowel disease (IBD) colitis have a 2.4 fold higher risk of developing colorectal cancer (CRC) than the general population, for both ulcerative colitis (UC) and Crohn's disease (CD) colitis. Surveillance colonoscopy is recommended to detect early CRC and dysplasia. Most dysplasia discovered in patients with IBD is actually visible. Recently published SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations) consensus statements provide unifying recommendations for the optimal surveillance and management of dysplasia in IBD. SCENIC followed the prescribed processes for guideline development from the Institute of Medicine (USA), including systematic reviews, full synthesis of evidence and deliberations by panelists, and incorporation of the GRADE methodology. The new surveillance paradigm involves high-quality visual inspection of the mucosa, using chromoendoscopy and high-definition colonoscopy, with endoscopic recognition of colorectal dysplasia. Lesions are described according to a new classification, which replaces the term 'dysplasia associated lesion or mass (DALM)' and its derivatives. Targeted biopsies are subsequently done on areas suspicious for dysplasia, and resections are carried out for discrete, resectable lesions. PMID- 26866421 TI - Interventions to optimise prescribing for older people in care homes. AB - BACKGROUND: There is a substantial body of evidence that prescribing for care home residents is suboptimal and requires improvement. Consequently, there is a need to identify effective interventions to optimise prescribing and resident outcomes in this context. This is an update of a previously published review (Alldred 2013). OBJECTIVES: The objective of the review was to determine the effect of interventions to optimise overall prescribing for older people living in care homes. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (including the Cochrane Effective Practice and Organisation of Care (EPOC) Specialised Register), MEDLINE, EMBASE and CINAHL to May 2015. We also searched clinical trial registries for relevant studies. SELECTION CRITERIA: We included randomised controlled trials evaluating interventions aimed at optimising prescribing for older people (aged 65 years or older) living in institutionalised care facilities. Studies were included if they measured one or more of the following primary outcomes: adverse drug events; hospital admissions; mortality; or secondary outcomes, quality of life (using validated instrument); medication-related problems; medication appropriateness (using validated instrument); medicine costs. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. We presented a narrative summary of results. MAIN RESULTS: The 12 included studies involved 10,953 residents in 355 (range 1 to 85) care homes in ten countries. Nine studies were cluster-randomised controlled trials and three studies were patient-randomised controlled trials. The interventions evaluated were diverse and often multifaceted. Medication review was a component of ten studies. Four studies involved multidisciplinary case-conferencing, five studies involved an educational element for health and care professionals and one study evaluated the use of clinical decision support technology. We did not combine the results in a meta-analysis due to heterogeneity across studies. Interventions to optimise prescribing may lead to fewer days in hospital (one study out of eight; low certainty evidence), a slower decline in health-related quality of life (one study out of two; low certainty evidence), the identification and resolution of medication-related problems (seven studies; low certainty evidence), and may lead to improved medication appropriateness (five studies out of five studies; low certainty evidence). We are uncertain whether the intervention improves/reduces medicine costs (five studies; very low certainty evidence) and it may make little or no difference on adverse drug events (two studies; low certainty evidence) or mortality (six studies; low certainty evidence). The risk of bias across studies was heterogeneous. AUTHORS' CONCLUSIONS: We could not draw robust conclusions from the evidence due to variability in design, interventions, outcomes and results. The interventions implemented in the studies in this review led to the identification and resolution of medication-related problems and improvements in medication appropriateness, however evidence of a consistent effect on resident related outcomes was not found. There is a need for high-quality cluster randomised controlled trials testing clinical decision support systems and multidisciplinary interventions that measure well-defined, important resident related outcomes. PMID- 26866422 TI - New insights into rotating frame relaxation at high field. AB - Measurements of spin-lock relaxation rates in the rotating frame (R1rho ) at high magnetic fields afford the ability to probe not only relatively slow molecular motions, but also other dynamic processes, such as chemical exchange and diffusion. In particular, measurements of the variation (or dispersion) of R1rho with locking field allow the derivation of quantitative parameters that describe these processes. Measurements in deuterated solutions demonstrate the manner and degree to which exchange dominates relaxation at high fields (4.7 T, 7 T) in simple solutions, whereas temperature and pH are shown to be very influential factors affecting the rates of proton exchange. Simulations and experiments show that multiple exchanging pools of protons in realistic tissues can be assumed to behave independently of each other. R1rho measurements can be combined to derive an exchange rate contrast (ERC) that produces images whose intensities emphasize protons with specific exchange rates rather than chemical shifts. In addition, water diffusion in the presence of intrinsic susceptibility gradients may produce significant effects on R1rho dispersions at high fields. The exchange and diffusion effects act independently of each other, as confirmed by simulation and experimentally in studies of red blood cells at different levels of oxygenation. Collectively, R1rho measurements provide an ability to quantify exchange processes, to provide images that depict protons with specific exchange rates and to describe the microstructure of tissues containing magnetic inhomogeneities. As such, they complement traditional T1 or T2 measurements and provide additional insights from measurements of R1rho at a single locking field. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26866423 TI - The 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Should Include New Standards for Hepatitis B Screening: Comment on the Article by Singh et al. PMID- 26866424 TI - Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices. AB - OBJECTIVE: To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis. METHODS: A total of 110 SSc patients (102 females and 8 males, mean +/- SD age 50.5 +/- 11.9 years), 110 age- and sex-matched RA patients, and 51 HS without CV disease were examined with ultrasonography (US). Carotid intima-media thickness (cIMT) >0.90 mm and/or carotid plaques were used as the gold standard for subclinical atherosclerosis (US+). Systematic Coronary Risk Evaluation (SCORE), QRisk II, and 2013 American College of Cardiology (ACC)/American Heart Association (AHA) CV risk indices were calculated. RESULTS: Twenty-one (19.1%) SSc patients, 24 (21.8%) RA patients, and 3 (5.9%) HS had subclinical atherosclerosis (SSc versus RA: P = 0.62, SSc versus HS: P = 0.029). cIMT in SSc was higher compared to HS (0.68 +/- 0.15 mm versus 0.61 +/- 0.10 mm; P = 0.008) but similar to RA patients (0.66 +/- 0.14 mm; P = 0.82). Subclinical atherosclerosis in SSc was associated with age (odds ratio [OR] 1.07, P = 0.013), elevated erythrocyte sedimentation rate (OR 3.4, P = 0.045), and pulmonary arterial hypertension (OR 4.27, P = 0.012). Concerning CV risk indices, of the 21 US+ SSc patients only 0, 3 (14.2%), and 6 (28.6%) were classified as high CV risk according to SCORE, QRisk II, and ACC/AHA risk indices, respectively. CONCLUSION: Subclinical atherosclerosis in SSc patients is more frequent than in HS, but is as frequent as in RA patients in which accelerated atherosclerosis is clearly defined. CV risk indices for the general population are considerably insufficient to detect SSc patients with atherosclerosis. PMID- 26866425 TI - Thalassemia: a look to the future. AB - To assess the future of a clinical science one must first assess the rate of accrual of understanding in the past century. From the time of Cooley's description (1925) to 1964, the year of the first Symposium, progress was glacial because the molecular biology revolution in medicine was in its infancy and therapy other than transfusion was impossible. But between 1964 and 2015, progress has been huge on every front. Our patients ushered in the molecular biology revolution in medicine. They have benefited from far better understanding of molecular pathophysiology, substantial improvements in transfusion and chelation, more effective stem cell transplantation, the beginnings of gene therapy, and now major advances in our capacity to reinduce fetal hemoglobin. We have only lagged in the application of prevention technology in the less developed world that suffers the most from thalassemia and sickle cell disease. We must redouble our efforts to spare patients from these cruel diseases. PMID- 26866426 TI - Global public awareness of venous thromboembolism: reply. PMID- 26866428 TI - Stopping Tumor Necrosis Factor Inhibitor Treatment in Patients With Established Rheumatoid Arthritis in Remission or With Stable Low Disease Activity: A Pragmatic Multicenter, Open-Label Randomized Controlled Trial. AB - OBJECTIVE: Tumor necrosis factor inhibitor (TNFi) biologic agents are an effective treatment for rheumatoid arthritis (RA). It is unclear whether patients whose disease is in remission or who have stable low disease activity need to continue use of TNFi or can stop this treatment. This study was undertaken to assess whether patients with established RA who are in remission or have stable low disease activity can effectively and safely stop their TNFi therapy. METHODS: The study was designed as a pragmatic multicenter, open-label randomized controlled trial. Inclusion criteria were a diagnosis of RA according to the American College of Rheumatology 1987 classification criteria, as well as use of a TNFi for at least 1 year along with a stable dose of disease-modifying antirheumatic drugs and a Disease Activity Score in 28 joints (DAS28) of <3.2 over the 6 months preceding trial inclusion. Patients were randomized in a 2:1 ratio to either stop or continue treatment with their current TNFi. Flare was defined as a DAS28 of >=3.2 during the 12-month follow-up period and an increase in score of >=0.6 compared to the baseline DAS28. RESULTS: In total, 531 patients were allocated to the stop group and 286 to the TNFi continuation group. At 12 months, more patients had experienced a flare in the stop group (272 [51.2%] of 531) than in the continuation group (52 [18.2%] of 286; P < 0.001). The hazard ratio for occurrence of a flare after stopping TNFi was 3.50 (95% confidence interval [95% CI] 2.60-4.72). The mean DAS28 in the stop group was significantly higher during the follow-up period compared to that in the continuation group (P < 0.001). Of the 195 patients who restarted TNFi treatment after experiencing a flare and within 26 weeks after stopping, 165 (84.6%) had regained a DAS28 of <3.2 by 6 months later, and the median time to a regained DAS28 of <3.2 was 12 weeks (95% Cl 10.7-13.3). There were more hospitalizations in the stop group than in the continuation group (6.4% versus 2.4%). CONCLUSION: Stopping TNFi treatment results in substantially more flares than does continuation of TNFi in patients with established RA in remission or with stable low disease activity. PMID- 26866429 TI - Flaxseed flour, compared to flaxseed oil, contributes to femoral structure in male rats subjected to early weaning. AB - The aim of this study was to analyze whether flaxseed flour or flaxseed oil treatment contributes to femoral structure in male rats subjected to early weaning. Pups were weaned for separation from mothers at 14 days (early weaning, EW) or 21 days (control, C). After 21 days, the control (C60) was fed with the control diet. The EW group was divided based on control (EWC60), flaxseed flour (EWFF60) and flaxseed oil (EWFO60) diets until 60 days. Femoral dimension, bone mineral density (BMD), bone mineral content (BMC), area and biomechanical properties were determined. EWFO60 showed lower (P < 0.05) femur mass. EWC60 and EWFO60 showed lower (P < 0.05) distance between epiphyses, diaphysis width and BMD. BMC was lower (P < 0.05) in EWC60 (vs. C60 and EWFF60). EWC60 and EWFO60 showed lower (P < 0.05) maximum force (vs. C60). Breaking strength was lower (P < 0.05) in EWFO60 (vs. C60). EWFF60 showed higher (P < 0.05) rigidity. Flaxseed flour abbreviated the femoral fragility secondary to early weaning. PMID- 26866427 TI - Molecular Analysis of Neutrophil Differentiation from Human Induced Pluripotent Stem Cells Delineates the Kinetics of Key Regulators of Hematopoiesis. AB - In vitro generation of mature neutrophils from human induced pluripotent stem cells (iPSCs) requires hematopoietic progenitor development followed by myeloid differentiation. The purpose of our studies was to extensively characterize this process, focusing on the critical window of development between hemogenic endothelium, hematopoietic stem/progenitor cells (HSPCs), and myeloid commitment, to identify associated regulators and markers that might enable the stem cell field to improve the efficiency and efficacy of iPSC hematopoiesis. We utilized a four-stage differentiation protocol involving: embryoid body (EB) formation (stage-1); EB culture with hematopoietic cytokines (stage-2); HSPC expansion (stage-3); and neutrophil maturation (stage-4). CD34(+) CD45(-) putative hemogenic endothelial cells were observed in stage-3 cultures, and expressed VEGFR-2/Flk-1/KDR and VE-cadherin endothelial markers, GATA-2, AML1/RUNX1, and SCL/TAL1 transcription factors, and endothelial/HSPC-associated microRNAs miR-24, miR-125a-3p, miR-126/126*, and miR-155. Upon further culture, CD34(+) CD45(-) cells generated CD34(+) CD45(+) HSPCs that produced hematopoietic CFUs. Mid-stage 3 CD34(+) CD45(+) HSPCs exhibited increased expression of GATA-2, AML1/RUNX1, SCL/TAL1, C/EBPalpha, and PU.1 transcription factors, but exhibited decreased expression of HSPC-associated microRNAs, and failed to engraft in immune deficient mice. Mid-stage-3 CD34(-) CD45(+) cells maintained PU.1 expression and exhibited increased expression of hematopoiesis-associated miR-142-3p/5p and a trend towards increased miR-223 expression, indicating myeloid commitment. By late Stage-4, increased CD15, CD16b, and C/EBPE expression were observed, with 25%-65% of cells exhibiting morphology and functions of mature neutrophils. These studies demonstrate that hematopoiesis and neutrophil differentiation from human iPSCs recapitulates many features of embryonic hematopoiesis and neutrophil production in marrow, but reveals unexpected molecular signatures that may serve as a guide for enhancing iPSC hematopoiesis. Stem Cells 2016;34:1513-1526. PMID- 26866431 TI - Allergen component analysis as a tool in the diagnosis of occupational allergy. AB - PURPOSE OF REVIEW: Rapid developments have been seen in molecular allergy diagnosis, based on the detection and quantification of specific IgE to single allergens. This review summarizes and discusses studies on allergen component analysis as a tool in the diagnosis of occupational allergy. RECENT FINDINGS: More than 400 agents are identified as sensitizers of occupational asthma, but only very few are characterized on the molecular level and available for routine diagnosis. Baker's asthma is one of the most frequently occurring forms of occupational asthma caused by workplace-related inhalation of cereal flour mainly wheat. Wheat sensitization profiles of bakers show great interindividual variability and no wheat allergen could be classified as the major allergen. Component-resolved diagnosis is a useful tool for diagnosing natural rubber latex (NRL) allergy. In cases with unexpected high-latex IgE but without clinical symptoms application of crossreactive carbohydrate determinants are helpful to clarify the cause of IgE binding. SUMMARY: Latex is an excellent model for component-resolved diagnosis and demonstrates well how to improve the diagnosis by using single allergens. For diagnosis of baker's asthma, a whole wheat extract is still the best option for specific IgE determination, but single wheat allergens might help to discriminate between wheat-induced food allergy, grass pollen allergy, and baker's asthma. New diagnostic tools and platforms are promising, but further knowledge of molecules relevant for occupational asthma (as in wood dust allergens, enzymes, laboratory animal allergens, etc.) and for occupational hypersensitivity pneumonitis is necessary to improve and standardize the diagnostic tools. PMID- 26866430 TI - Lexical processing and organization in bilingual first language acquisition: Guiding future research. AB - A rich body of work in adult bilinguals documents an interconnected lexical network across languages, such that early word retrieval is language independent. This literature has yielded a number of influential models of bilingual semantic memory. However, extant models provide limited predictions about the emergence of lexical organization in bilingual first language acquisition (BFLA). Empirical evidence from monolingual infants suggests that lexical networks emerge early in development as children integrate phonological and semantic information. These findings tell us little about the interaction between 2 languages in early bilingual memory. To date, an understanding of when and how languages interact in early bilingual development is lacking. In this literature review, we present research documenting lexical-semantic development across monolingual and bilingual infants. This is followed by a discussion of current models of bilingual language representation and organization and their ability to account for the available empirical evidence. Together, these theoretical and empirical accounts inform and highlight unexplored areas of research and guide future work on early bilingual memory. (PsycINFO Database Record PMID- 26866432 TI - Development of a Theory-Based Intervention to Increase Clinical Measurement of Reactive Balance in Adults at Risk of Falls. AB - BACKGROUND: Effective balance reactions are essential for avoiding falls, but are not regularly measured by physical therapists. Physical therapists report wanting to improve reactive balance assessment, and theory-based approaches are recommended as the foundation for the development of interventions. This article describes how a behavior change theory for health care providers, the theoretical domains framework (TDF), was used to develop an intervention to increase reactive balance measurement among physical therapists who work in rehabilitation settings and treat adults who are at risk of falls. CASE DESCRIPTION: We employed published recommendations for using the TDF-guided intervention development. We identified what health care provider behavior is in need of change, relevant barriers and facilitators, strategies to address them, and how we would measure behavior change. In this case, identifying strategies required selecting both a reactive balance measure and behavior change techniques. Previous research had determined that physical therapists need to increase reactive balance measurement, and identified barriers and facilitators that corresponded to 8 TDF domains. A published review informed the selection of the Balance Evaluation Systems Test (Reactive Postural Responses Section) as addressing the barriers and facilitators, and existing research informed the selection of 9 established behavior change techniques corresponding to each identified TDF domain. OUTCOMES: The TDF framework were incorporated into a 12-month intervention with interactive group sessions, local champions, and health record modifications. Intervention effect can be evaluated using health record abstraction, questionnaires, and qualitative semistructured interviews. SUMMARY: Although future research will evaluate the intervention in a controlled study, the process of theory-based intervention development can be applied to other rehabilitation research contexts, maximizing the impact of this work.Video Abstract is available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A123). PMID- 26866433 TI - Impact of a prophylactic combination of dexamethasone-ondansetron on postoperative nausea and vomiting in obese adult patients undergoing laparoscopic sleeve gastrectomy during closed-loop propofol-remifentanil anaesthesia: A randomised double-blind placebo-controlled study. AB - BACKGROUND: In obese patients, the incidence of postoperative nausea and vomiting (PONV) following sleeve gastrectomy under titration of total intravenous anaesthesia (TIVA) and the relevance of risk factors to indicate prophylaxis is unknown. OBJECTIVES: The hypothesis was that after automated TIVA, prophylaxis reduces PONV following laparoscopic sleeve gastrectomy. Our objective was to determine the incidence of PONV and evaluate the efficacy of dexamethasone and ondansetron as prophylaxis when automated intravenous anaesthesia is employed. DESIGN: A randomised, placebo-controlled, single-centre, double-blinded study. SETTING: Secondary care centre in New Caledonia from June 2013 to January 2014. PATIENTS: A total of 122 patients were randomised and 117 (92 women) were included in the analysis (58 in the prophylaxis group and 59 in the placebo group). Eligibility criteria included at least two of the known risk factors for PONV: female sex, nonsmoking status, prior history of PONV or motion sickness and expected postoperative opioid analgesia. Exclusion criteria included disorders limiting the use of the bispectral index. INTERVENTIONS: All patients received propofol and remifentanil controlled by the same automated system during induction and maintenance of general anaesthesia. The controller modifies the calculated effect-site concentrations according to bispectral index values. Patients received either intravenous dexamethasone 4 mg after tracheal intubation and ondansetron 4 mg during skin closure, or placebo. MAIN OUTCOME MEASURES: The primary endpoint was the cumulative incidences of 24-h PONV and severe PONV (vomiting or nausea with a score of >=4 on an 11-point verbal rating scale). Data are presented as percentage (95% confidence interval). RESULTS: PONV in the first 24 h occurred in 45 (34 to 60)% of patients who received prophylaxis and 54 (41 to 67)% in the placebo group (P = 0.35). The numbers of patients who suffered severe PONV [19 (10 to 32)% in the prophylaxis group vs. 20 (11 to 33)%, P = 1, in the placebo group] and who required rescue antiemetic drugs [55 (41 to 68) vs. 63 (49 to 75)%, P = 0.46] were similar between the groups. CONCLUSION: The combination of dexamethasone and ondansetron was not effective in preventing PONV or severe PONV in obese patients undergoing laparoscopic sleeve gastrectomy after TIVA. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01876290. PMID- 26866434 TI - CHORIORETINAL BIOPSY FOR THE DIAGNOSIS OF ENDOGENOUS ENDOPHTHALMITIS DUE TO ESCHERICHIA COLI. AB - PURPOSE: To describe the novel use of a chorioretinal biopsy technique to confirm the microbiological diagnosis of endogenous Escherichia coli (E. coli) endophthalmitis, when other investigations have been proven nondiagnostic. METHODS: Case report of an 82-year-old white man with endogenous endophthalmitis without a clearly identifiable source of infection. RESULTS: After systemic cultures and multiple aqueous and vitreous samples were unable to identify a causative organism, chorioretinal biopsy of a subretinal abscess was used to confirm the microbiological diagnosis. This ensured appropriate ophthalmic and systemic treatment of infection. CONCLUSION: Endogenous E. coli endophthalmitis is a rare and aggressive condition usually seen in patients with insulin dependent diabetes with concurrent urinary tract infection. This case demonstrates chorioretinal biopsy to be a viable and effective method of establishing a firm microbiological diagnosis in cases of culture-negative endophthalmitis. PMID- 26866435 TI - A Retrospective Review of the Presentation and Treatment of Stingray Stings Reported to a Poison Control System. AB - We studied stingray stings reported to our poison system to identify associated complications and treatments. We undertook a 14-year retrospective observational analysis of stingray stings reported to our poison system. Extracted data included caller age and gender, outcome, management site, symptoms, treatments, and geographical location of the sting. We examined suspected infection rate, hot water treatment efficacy, and possible presence of foreign bodies in the wound. Suspected infection rate was defined as "possible infection" or "likely infection." Hot water treatment efficacy was defined as cases that encoded hot water as a treatment and noted pain relief within 1 hour of treatment in the free text record, before documentation of other analgesic administration. A total of 576 envenomations were reported. The majority were men (76%), with an average age of 24 years (range, 6-78 years). Symptoms were reported in 485 cases. A total of 9% recorded a foreign body or debris at the wound site. Symptoms included pain (79%), puncture wound (65%), and edema (25%). Infections were reported in 9% of cases. Hot/warm water immersion appeared effective for pain relief in 69% of cases where outcome was documented. The most common geographical location of stingray envenomations was Southern California. Stingray stings are common in California. Hot/warm water seemed to be effective in pain management in our series, whereas foreign bodies or retained spines and infections were other identified complications. PMID- 26866436 TI - Expression of Matrix Metalloproteinases-2/-9 is Associated With Microvessel Density in Pancreatic Cancer. AB - This study aimed to investigate the association of matrix-metalloproteinase (MMP) 2 and MMP-9 with microvessel density (MVD) in pancreatic cancer. The tumor tissues and para-tumor tissues of 30 patients with pancreatic cancer were pathologically examined. The normal pancreatic tissues of another 17 patients served as controls. The expression of MMP-2 and MMP-9 was examined using immunohistochemistry and scored. The association of MMP-2 and MMP-9 with the MVD values and pathological features were analyzed. The positive expression rates of MMP-2 and MMP-9 in the tumor tissues were significantly higher than those in the para-tumor tissues (P < 0.01). In normal pancreatic tissues, both MMP-2 and MMP-9 expressions were negative. The MVD values increased significantly along with higher tumor node metastasis stages (P = 0.04). The MVD values were positively correlated with MMP-2 scores (r = 0.563, P < 0.05) and MMP-9 scores (r = 0.451, P < 0.05). The expression of MMP-2 and MMP-9 is associated with angiogenesis in pancreatic cancer. MMPs might be used as prognostic factors and therapy targets for patients with pancreatic cancer. PMID- 26866437 TI - Prognostic Importance of Controlling Nutritional Status in Patients Undergoing Curative Thoracoscopic Esophagectomy for Esophageal Cancer. AB - It is now clear that cancer survival is determined not only by tumor pathology but also by host-related factors, in particular, nutritional status and systemic inflammation. It is desirable that the essential properties of any scale designed or intended to be used for the prediction of survival are simple, convenient, and objective. In this study, we retrospectively reviewed the database of patients who underwent curative surgery for esophageal cancer in our department to evaluate controlling nutritional status (CONUT) and neutrophil-lymphocyte ratio (NLR) as predictors of cancer-specific survival (CSS) after esophagectomy. We retrospectively reviewed the database of 148 consecutive patients who underwent potentially curative surgery for histologically verified esophageal squamous cell carcinoma at our institute between January 2002 and December 2014. CONUT and NLR were calculated. On multivariate analysis, pTNM stage (P < 0.0001) and CONUT (P = 0.0291) were independently associated with worse prognosis. Multivariate analysis evaluated the prognostic factors in 2 different patient groups: patients younger than 70 years (nonelderly) and those aged 70 years or more (elderly). Multivariate analysis demonstrated that pTNM stage (P = 0.0083) and CONUT (P = 0.0138) were the independent risk factors for a worse prognosis among the nonelderly group, whereas univariate analysis demonstrated that pTNM stage (P = 0.0002) was the only independent risk factor for a worse prognosis among the elderly group. CONUT was a significant predictor of CSS in patients with esophageal cancer in this study. However, pTNM stage remained a significantly more powerful predictor of CSS. Therefore, the results of this study suggested that CONUT and pTNM stage are the significant and complementary factors predicting survival in patients with esophageal cancer. But, this study failed to confirm the NLR as a significant predictor of CSS after resection for esophageal cancer. PMID- 26866438 TI - High-Power Prismatic Devices for Oblique Peripheral Prisms. AB - PURPOSE: Horizontal peripheral prisms for hemianopia provide field expansion above and below the horizontal meridian; however, there is a vertical gap leaving the central area (important for driving) without expansion. In the oblique design, tilting the bases of both prism segments toward the horizontal meridian moves the field expansion area vertically and centrally (closing the central gap) while the prisms remain in the peripheral location. However, tilting the prisms results also in a reduction of the lateral field expansion. Higher prism powers are needed to counter this effect. METHODS: We developed, implemented, and tested a series of designs aimed at increasing the prism power to reduce the central gap while maintaining wide lateral expansion. The designs included inserting the peripheral prisms into carrier lenses that included yoked prism in the opposite direction, combination of two Fresnel segments attached at the base and angled to each other (bi-part prisms), and creating Fresnel prism-like segments from nonparallel periscopic mirror pairs (reflective prisms). RESULTS: A modest increase in lateral power was achieved with yoked-prism carriers. Bi-part combination of 36Delta Fresnel segments provided high power with some reduction in image quality. Fresnel reflective prism segments have potential for high power with superior optical quality but may be limited in field extent or by interruptions of the expanded field. Extended apical scotomas, even with unilateral fitting, may limit the utility of very high power prisms. The high power bi-part and reflective prisms enable a wider effective eye scanning range (more than 15 degrees) into the blind hemifield. CONCLUSIONS: Conventional prisms of powers higher than the available 57Delta are limited by the binocular impact of a wider apical scotoma and a reduced effective eye scanning range to the blind side. The various designs that we developed may overcome these limitations and find use in various other field expansion applications. PMID- 26866440 TI - Heading to the right: The effect of aperture width on navigation asymmetries for miniature remote-controlled vehicles. AB - Our ability to attend to the environment is asymmetrical and affects activities like navigation. This study investigated whether rightward deviations exist for miniaturized vehicles. Experiment 1 asked participants (n = 26) to navigate a remote-controlled car through apertures that were 200, 300 or 400 mm wide. Analyses revealed a nonsignificant trend for the rightward deviation to increase with aperture width. None of the deviations was significantly to the right. Experiment 2 (n = 16) elevated the car to eye level to control for upper/lower visual-field effects. The results were unchanged. Experiment 3 (n = 16) altered the car's mechanical drive to control veering effects, and the results were unchanged. Data from Experiments 1-3 were combined to increase statistical power and showed that the rightward deviation increased for wider apertures. Experiment 4 (n = 17) investigated deviations for wider apertures (1,100 mm) and found a rightward deviation. Finally, Experiment 5 (n = 24) used a different type of remote-controlled vehicle. A rightward deviation, which increased with width, was observed. In addition, the degree of rightward deviation was related to the perceived middle of the aperture. It appears that systematic rightward deviations occur for miniaturized vehicles, which increase with aperture width. The implications of these results for attentional explanations of rightward deviation are discussed. (PsycINFO Database Record PMID- 26866439 TI - The Prevalence of Latent Tuberculosis Infection in the United States. AB - RATIONALE: Individuals with latent tuberculosis infection (LTBI) represent a reservoir of infection, many of whom will progress to tuberculosis (TB) disease. A central pillar of TB control in the United States is reducing this reservoir through targeted testing and treatment. OBJECTIVES: To estimate the prevalence of LTBI in the United States using the tuberculin skin test (TST) and an IFN-gamma release assay. METHODS: We used nationally representative data from the 2011-2012 National Health and Nutrition Examination Survey (n = 6,083 aged >=6 yr). LTBI was measured by both the TST and QuantiFERON-TB Gold In-Tube test (QFT-GIT). Weighted population, prevalence, and multiple logistic regression were used. MEASUREMENTS AND MAIN RESULTS: The estimated prevalence of LTBI in 2011-2012 was 4.4% as measured by the TST and 4.8% by QFT-GIT, corresponding to 12,398,000 and 13,628,000 individuals, respectively. Prevalence declined slightly since 2000 among the U.S. born but remained constant among the foreign born. Earlier birth cohorts consistently had higher prevalence than more recent ones. Higher risk groups included the foreign born, close contact with a case of TB disease, and certain racial/ethnic groups. CONCLUSIONS: After years of decline, the prevalence of LTBI remained relatively constant between 2000 and 2011. A large reservoir of 12.4 million still exists, with foreign-born persons representing an increasingly larger proportion of this reservoir (73%). Estimates and risk factors for LTBI were generally similar between the TST and QFT-GIT. The updated estimates of LTBI and associated risk groups can help improve targeted testing and treatment in the United States. PMID- 26866441 TI - Prejudice toward individuals with obesity: Evidence for a pro-effort bias. AB - Three studies examined the role of causal beliefs in weight stigma in order to better understand people's evaluations of individuals with obesity. Participants viewed weight-related information about a target individual and evaluated that target on various dimensions. Study 1 showed that offset effort information (i.e., information about effort to lose weight) had a greater impact on participants' evaluations of individuals with obesity than did other causal information, such as onset control and offset ability. Study 2 extended this finding by demonstrating that the duration of effort invested to lose weight is also important in determining participants' evaluations of individuals with obesity. Study 3 replicated the effect of effort (albeit in terms of effort to maintain a healthy lifestyle) on evaluations of individuals without obesity. Furthermore, in all 3 studies, disgust mediated the association between perceived effort and desire for social distance from the target. These findings highlight a key role for effort and disgust in weight stigma, and suggest that the negative evaluations of individuals with obesity might in part reflect a pro-effort bias. The present research has important implications for strategies to reduce weight stigma, and may even inform strategies to reduce social stigma beyond obesity, such as drug addiction. (PsycINFO Database Record PMID- 26866442 TI - Vertical 2D/3D Semiconductor Heterostructures Based on Epitaxial Molybdenum Disulfide and Gallium Nitride. AB - When designing semiconductor heterostructures, it is expected that epitaxial alignment will facilitate low-defect interfaces and efficient vertical transport. Here, we report lattice-matched epitaxial growth of molybdenum disulfide (MoS2) directly on gallium nitride (GaN), resulting in high-quality, unstrained, single layer MoS2 with strict registry to the GaN lattice. These results present a promising path toward the implementation of high-performance electronic devices based on 2D/3D vertical heterostructures, where each of the 3D and 2D semiconductors is both a template for subsequent epitaxial growth and an active component of the device. The MoS2 monolayer triangles average 1 MUm along each side, with monolayer blankets (merged triangles) exhibiting properties similar to that of single-crystal MoS2 sheets. Photoluminescence, Raman, atomic force microscopy, and X-ray photoelectron spectroscopy analyses identified monolayer MoS2 with a prominent 20-fold enhancement of photoluminescence in the center regions of larger triangles. The MoS2/GaN structures are shown to electrically conduct in the out-of-plane direction, confirming the potential of directly synthesized 2D/3D semiconductor heterostructures for vertical current flow. Finally, we estimate a MoS2/GaN contact resistivity to be less than 4 Omega.cm(2) and current spreading in the MoS2 monolayer of approximately 1 MUm in diameter. PMID- 26866445 TI - Spectral Heart Rate Variability analysis using the heart timing signal for the screening of the Sleep Apnea-Hypopnea Syndrome. AB - Some approaches have been published in the past using Heart Rate Variability (HRV) spectral features for the screening of Sleep Apnea-Hypopnea Syndrome (SAHS) patients. However there is a big variability among these methods regarding the selection of the source signal and the specific spectral components relevant to the analysis. In this study we investigate the use of the Heart Timing (HT) as the source signal in comparison to the classical approaches of Heart Rate (HR) and Heart Period (HP). This signal has the theoretical advantage of being optimal under the Integral Pulse Frequency Modulation (IPFM) model assumption. Only spectral bands defined as standard for the study of HRV are considered, and for each method the so-called LF/HF and VLFn features are derived. A comparative statistical analysis between the different resulting methods is performed, and subject classification is investigated by means of ROC analysis and a Naive-Bayes classifier. The standard Apnea-ECG database is used for validation purposes. Our results show statistical differences between SAHS patients and controls for all the derived features. In the subject classification task the best performance in the testing set was obtained using the LF/HF ratio derived from the HR signal (Area under ROC curve=0.88). Only slight differences are obtained due to the effect of changing the source signal. The impact of using the HT signal in this domain is therefore limited, and has not shown relevant differences with respect to the use of the classical approaches of HR or HP. PMID- 26866446 TI - Gate-Sensing Coherent Charge Oscillations in a Silicon Field-Effect Transistor. AB - Quantum mechanical effects induced by the miniaturization of complementary metal oxide-semiconductor (CMOS) technology hamper the performance and scalability prospects of field-effect transistors. However, those quantum effects, such as tunneling and coherence, can be harnessed to use existing CMOS technology for quantum information processing. Here, we report the observation of coherent charge oscillations in a double quantum dot formed in a silicon nanowire transistor detected via its dispersive interaction with a radio frequency resonant circuit coupled via the gate. Differential capacitance changes at the interdot charge transitions allow us to monitor the state of the system in the strong-driving regime where we observe the emergence of Landau-Zener-Stuckelberg Majorana interference on the phase response of the resonator. A theoretical analysis of the dispersive signal demonstrates that quantum and tunneling capacitance changes must be included to describe the qubit-resonator interaction. Furthermore, a Fourier analysis of the interference pattern reveals a charge coherence time, T2 ~ 100 ps. Our results demonstrate charge coherent control and readout in a simple silicon transistor and open up the possibility to implement charge and spin qubits in existing CMOS technology. PMID- 26866447 TI - Advances in stent-mediated gene delivery. PMID- 26866448 TI - A Novel Splicing Mutation Identified in a Chinese Family with X-linked Alport Syndrome Using Targeted Next-Generation Sequencing. AB - AIMS: Alport syndrome (AS) is a genetically heterogeneous disorder, characterized by hematuria, progressive renal failure, sensorineural hearing loss, and ocular abnormalities caused by mutations in the COL4A3, COL4A4, and COL4A5 genes. The aim of this study was to identify underlying mutations in individuals from a Chinese family with X-linked AS. METHODS: We performed targeted next-generation sequencing (NGS) to identify mutations associated with AS. The results were processed and visualized using an Integrated Genomics Viewer software. The most likely disease-causing variants were identified and confirmed by Sanger sequencing of reverse transcription-polymerase chain reaction products. RESULTS: Visual inspection using Integrative Genomics Viewer software found that COL4A5 exon 10 was not covered by the disease panel, while coverage of exons 4, 17, 20, 21, 37, and 45 was incomplete. Sanger sequencing of these regions identified a novel splice-site mutation in intron 9 (c.547-3C>A) of the COL4A5 gene. Subsequent cDNA analysis revealed that c.547-3C>A led to skipping of exon 10, which resulted in an in-frame deletion of 21 amino acids from the alpha5 chain of type IV collagen. CONCLUSION: We determined the molecular basis of AS in a Chinese family by targeted NGS and cDNA analysis. This is the first report of the novel c.547-3C>A splicing mutation in the collagen domain of COL4A5 gene. PMID- 26866449 TI - Interspecific differences in the antioxidant capacity of two Laridae species exposed to metals. AB - The main aim of the present study was to assess the concentration of metals (Pb, Cd, Hg, Cu and Zn) in blood, and elucidate their potential effects on oxidative stress biomarkers in red blood cells of Audouin's gull (Ichthyaetus audouinii) and Slender-billed gull (Chroicocephalus genei) chicks in Southeastern Spain. For this purpose, total glutathione (GSH) content, antioxidant enzymes activities (glutathione peroxidase, GPx; superoxide dismutase, SOD; catalase, CAT and glutathione-S-transferase, GST), and lipid peroxidation (TBARS) were analyzed. In general, metal exposure in both species can be considered low, except for Hg in Audouin's gull. Our findings show higher antioxidant levels in Audouin's gull than in Slender-billed gull; probably due to a combination of different basal antioxidant capacity between species, and to an up-regulation of the antioxidant system in Audouin's gull as a response to the higher Hg, Cu and Zn concentrations. This could reduce the production of TBARS keeping them at lower levels than those found in Slender-billed gull. In spite of this, the significantly higher Hg levels found in Audouin's gull (13.6ug/dl wet weight) in comparison to Slender-billed gull (2.7ug/dl), likely related to their different diet and the former consuming discarded fish, were able to produce lipid peroxidation in this species. The positive effect of Hg on SOD activity in Slender-billed gull, and of Pb on GSH levels in Audouin's gull, could reflect the necessity of the organism to upregulate these antioxidants to balance the increased oxidative stress caused by metals. The degree of metal exposure seems to be essential in the response of the antioxidant system, which may suffer up or down-regulations depending on metal concentrations. This study supports the interactive effects of metals on oxidative stress biomarkers, the complexity of the antioxidant system and the close cooperation between antioxidants, which requires the study of several metals and biomarkers to evaluate oxidative stress and damage in wild birds. PMID- 26866450 TI - Kidney function in sugarcane cutters in Nicaragua--A longitudinal study of workers at risk of Mesoamerican nephropathy. AB - BACKGROUND: Chronic kidney disease is common among sugarcane workers in Central America. The main risk factor seems to be repeated high-intensity work in hot environments. Several cross-sectional studies have been performed but few longitudinal studies. OBJECTIVES: The aim of the study was to examine whether kidney function changes over a few months of work during the harvest period. METHODS: A group of male sugarcane cutters in Nicaragua (N=29, aged 17-38 years) was examined with renal biomarkers before and after shift on the first day at the start of harvest, on the sixth day during acclimatization, and then in mid harvest 9 weeks later. A reference group (N=25, mainly office workers) was examined with the same biomarkers at start of harvest, and then at end of harvest 5 months later. RESULTS: The pre-shift renal function decreased significantly during 9 weeks of work in the cane cutters. Mean serum creatinine increased (20%), mean estimated glomerular filtration rate decreased (9%, 10mL/min), serum urea N (BUN) increased (41%), and mean urinary neutrophil gelatinase-associated lipocalin (NGAL) increased (four times). The cane cutters also developed cross shift increases in these biomarkers, in particular serum creatinine and BUN, and in urinary uric acid. The longitudinal decrease in eGFR tended to be associated with the cross-shift increase in serum creatinine. CONCLUSIONS: There was a remarkable decrease of glomerular kidney function, after only 9 weeks of harvest. The cross-shift increase in serum creatinine may be caused by dehydration (pre renal dysfunction), and when repeated on a daily basis this may cause permanently reduced GFR. PMID- 26866451 TI - Corrosion and tribocorrosion behavior of Ti-B4C composite intended for orthopaedic implants. AB - Poor wear resistance of titanium is a major concern since relative movements due to the cyclic loads in body environment cause wear between the bone and the implant material leading to detachment of the wear debris and release of metal ions due to the simultaneous action of corrosion and wear, defined as tribocorrosion. In order to increase the tribocorrosion resistance, Grade 2 Ti matrix 24vol% B4C particle reinforced composites were processed by hot pressing. Corrosion behaviour was investigated by electrochemical impedance spectroscopy and potentiodynamic polarization in 9g/L NaCl solution at body temperature. Tribocorrosion tests were performed under open circuit potential, as well as under potentiodynamic polarization using a reciprocating ball-on-plate tribometer. Results suggested that the addition of B4C particles provided lower tendency to corrosion and lower corrosion kinetics under sliding, along with significantly reduced wear loss, mainly due to the load carrying effect given by the reinforcement particles. PMID- 26866452 TI - A preliminary technical study on sodium dodecyl sulfate-induced changes of the nano-structural and macro-mechanical properties in human iliotibial tract specimens. AB - INTRODUCTION: Acellular scaffolds are frequently used for the surgical repair of ligaments and tendons. Even though data on the macro-mechanical properties related to the acellularization process exist, corresponding data on the nano structural properties are still lacking. Such data would help identify target proteins of the formed extracellular matrix that are chemically altered by the acellularization. In this study we examined the altered structure by comparing molecular properties of collagens from native and acellular iliotibial tract samples to the macroscopic stress-strain behavior of tract samples. MATERIAL AND METHODS: Matched pairs of five human iliotibial tract samples were obtained from five donors (mean age 28.2+/-4.7 years). One of each pair was acellularized using 1vol% sodium dodecyl sulfate (SDS) for 7 days. (13)C magic angle spinning nuclear magnetic resonance spectroscopy ((13)C CP MAS NMR) was utilized to compare the collagen overall secondary structure and internal dynamics of collagen-typical amino acid proteins. The resulting data was compared to age-matched stress-strain data of tract samples obtained in an uniaxial tensile setup and histologically. RESULTS: Typical and nearly identical collagen (13)C CP MAS NMR spectra were found in the tract samples before and after acellularization with SDS. The characteristic collagen backbone remained intact in the native and acellular samples. Collagen molecular composition was largely unaltered in both conditions. Furthermore, a similar dynamic behavior was found for the amino acids Hyp gamma, Pro alpha/Hyp alpha, Ala alpha, Gly alpha and Ala beta. These minute alterations in the collagens' molecular properties related to acellularization with SDS were in line with the similarly minute changes in the macro-mechanical tensile behavior, such as the elastic modulus and ultimate stress. Histology showed intact type I collagens, minute amounts of elastins before and after acellularization and evidence for acellularization-induced reductions of proteoglycans. DISCUSSION: Nano-structural properties of collagens are minutely affected by SDS treatment for acellularization, indicated by the molecular composition and dynamics. The lacking acellularization-related changes in the molecular structure properties of collagens in iliotibial tract samples are in line with the small alterations in their macro-mechanical tensile behavior. Though the given setup approaches soft tissue mechanics from both scaling extremes of mechanical testing, further structural analyzes are needed in a larger sample size to substantiate these findings. PMID- 26866453 TI - Adhesive strength of bioactive oxide layers fabricated on TNTZ alloy by three different alkali-solution treatments. AB - Bioactive oxide layers were fabricated on Ti-29Nb-13Ta-4.6Zr alloy (TNTZ) by three different alkali solution treatments: hydrothermal (H), electrochemical (E), and hydrothermal-electrochemical (HE). The adhesive strength of the oxide layer to the TNTZ substrate was measured to determine whether this process achieves sufficient adhesive strength for implant materials. Samples subjected to the HE process, in which a current of 15mA/cm(2) was applied at 90 degrees C for 1h (HE90-1h), exhibited a comparatively higher adhesive strength of approximately 18MPa while still maintaining a sufficiently high bioactivity. Based on these results, an oxide layer fabricated on TNTZ by HE90-1h is considered appropriate for practical biomaterial application, though thicker oxide layers with many cracks can lead to a reduced adhesive strength. PMID- 26866454 TI - Chinese medicines with sedative-hypnotic effects and their active components. AB - The main pharmacological effects of sedative agents are sedation, hypnosis, antianxiety, and antidepression. Traditional Chinese medicine (TCM) has a long history of clinical experience in treating insomnia. This review focuses mainly on the role of active ingredients from TCM in the treatment of insomnia. Single herbs and their active ingredients from TCM with hypnotic effects are summarized through reviewing the relevant literature published in the past 20 y. The active ingredients are divided into alkaloids, terpenoids, and volatile oils, flavonoids, lignanoids and coumarins, saponins, and others. Current studies on TCM in treating insomnia are described from the aspects of active ingredients, sources, experimental models and methods, results, and mechanisms. In addition, Chinese compound prescriptions developed from a variety of single herbs with sedative-hypnotic effects are introduced. The acting pathways of TCM are covered from the perspectives of regulating central neurotransmitters, influencing sleep related cytokines, and improving the structure of the central nervous system. PMID- 26866455 TI - Chiral pool synthesis and biological evaluation of C-furanosidic and acyclic LpxC inhibitors. AB - Inhibitors of the bacterial deacetylase LpxC have emerged as a promising new class of Gram-negative selective antibacterials. In order to find novel LpxC inhibitors, in chiral-pool syntheses starting from d-mannose, C-furanosides with altered configuration in positions 2 and/or 5 of the tetrahydrofuran ring were prepared in stereochemically pure form. Additionally, the substitution pattern in positions 3 and 4 of the tetrahydrofuran ring as well as the structure of the lipophilic side chain in position 2 were varied. Finally, all stereoisomers of the respective open chain diols were obtained via glycol cleavages of properly protected C-glycosides. The biological evaluation of the synthesized hydroxamic acids revealed that in case of the C-glycosides, 2,5-trans-configuration generally leads to superior inhibitory and antibacterial activities. The relief of the conformational strain leading to the respective open chain derivatives generally caused an increase in the inhibitory and antibacterial activities of the benzyloxyacetohydroxamic acids. With Ki-values of 0.35 MUm and 0.23 MUm, the (S,S)-configured open-chain derivatives 8b and 8c were found to be the most potent LpxC inhibitors of these series of compounds. PMID- 26866456 TI - Design, synthesis and biological evaluation of novel L-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors. AB - Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43). Moreover, we evaluated these novel compounds for their anti-influenza activities against A/WSN/33 virus in MDCK cells. Among all evaluated compounds, the 2,3-O,O-dibenzyl-6-deoxy-l ascorbic acid-betulinic acid conjugate (30) showed the most significant anti influenza activity with an EC50 of 8.7 MUM, and no cytotoxic effects on MDCK cells were observed. Time-of-addition assay indicated that compound 30 acted at an early stage of the influenza life cycle. Further analyses revealed that influenza virus-induced hemagglutination of chicken red blood cells was inhibited by treatment of compound 30, and the interaction between the influenza hemagglutinin (HA) and compound 30 was determined by surface plasmon resonance (SPR) with a dissociation constant of KD = 3.76 MUM. Finally, silico docking studies indicated that compound 30 and its derivative 31 were able to occupy the binding pocket of HA for sialic acid receptor. Collectively, these results suggested that l-ascorbic acid-conjugated pentacyclic triterpenes were promising anti-influenza entry inhibitors, and HA protein associated with viral entry was a promising drug target. PMID- 26866457 TI - Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships. AB - Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., beta-carotene-linoleic acid; DPPH(*), ABTS(*+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 +/- 1.06 MUM), superoxide (28.18 +/- 1.35% inhibition at 100 MUM) and CUPRAC (A0.5: 35.89 +/- 0.09 MUM) assays. Compound 5 (IC50: 11.02 +/- 0.02 MUM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 +/- 0.18 MUM) in beta-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 +/- 1.65 and 111.60 +/- 1.28 MUM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time. PMID- 26866458 TI - Synthesis and Characterization of Cleavable Core-Cross-Linked Micelles Based on Amphiphilic Block Copolypeptoids as Smart Drug Carriers. AB - Amphiphilic block copolypeptoids consisting of a hydrophilic poly(N-ethyl glycine) segment and a hydrophobic poly[(N-propargyl glycine)-r-(N-decyl glycine)] random copolymer segment [PNEG-b-P(NPgG-r-NDG), EPgD] have been synthesized by sequential primary amine-initiated ring-opening polymerization (ROP) of the corresponding N-alkyl N-carboxyanhydride monomers. The block copolypeptoids form micelles in water and the micellar core can be cross-linked with a disulfide-containing diazide cross-linker by copper-mediated alkyne-azide cycloaddition (CuAAC) in aqueous solution. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical micelles with uniform size for both the core-cross-linked micelles (CCLMs) and non-cross-linked micelles (NCLMs) precursors for selective block copolypeptoid polymers. The CCLMs exhibited increased dimensional stability relative to the NCLMs in DMF, a nonselective solvent for the core and corona segments. Micellar dissociation of CCLMs can be induced upon addition of a reducing agent (e.g., dithiothreitol) in dilute aqueous solutions, as verified by a combination of fluorescence spectroscopy, size exclusion chromatography (SEC), and (1)H NMR spectroscopic measurement. Doxorubicin (DOX), an anticancer drug, can be loaded into the hydrophobic core of CCLMs with a maximal 23% drug loading capacity (DLC) and 37% drug loading efficiency (DLE). In vitro DOX release from the CCLMs can be triggered by DTT (10 mM), in contrast to significantly reduced DOX release in the absence of DTT, attesting to the reductively responsive characteristic of the CCLMs. While the CCLMs exhibited minimal cytotoxicity toward HepG2 cancer cells, DOX-loaded CCLMs inhibited the proliferation of the HepG2 cancer cells in a concentration and time dependent manner, suggesting the controlled release of DOX from the DOX-loaded CCLMS in the cellular environment. PMID- 26866460 TI - The Interplay Between Bioenergy Grass Production and Water Resources in the United States of America. AB - We apply a land surface model to evaluate the interplay between potential bioenergy grass (Miscanthus, Cave-in-Rock, and Alamo) production, water quantity, and nitrogen leaching (NL) in the Central and Eastern U.S. Water use intensity tends to be lower where grass yields are modeled to be high, for example in the Midwest for Miscanthus and Cave-in-Rock and the upper southeastern U.S. for Alamo. However, most of these regions are already occupied by crops and forests and substitution of these biome types for ethanol production implies trade-offs. In general, growing Miscanthus consumes more water, Alamo consumes less water, and Cave-in-Rock consumes approximately the same amount of water as existing vegetation. Bioenergy grasses can maintain high productivity over time, even in water limited regions, because their roots can grow deeper and extract the water from the deep, moist soil layers. However, this may not hold where there are frequent and intense drought events, particularly in regions with shallow soil depths. One advantage of bioenergy grasses is that they mitigate nitrogen leaching relative to row crops and herbaceous plants when grown without applying N fertilizer; and bioenergy grasses, especially Miscanthus, generally require less N fertilizer application than row crops and herbaceous plants. PMID- 26866459 TI - Structural Insights into the Activation of Human Relaxin Family Peptide Receptor 1 by Small-Molecule Agonists. AB - The GPCR relaxin family peptide receptor 1 (RXFP1) mediates the action of relaxin peptide hormone, including its tissue remodeling and antifibrotic effects. The peptide has a short half-life in plasma, limiting its therapeutic utility. However, small-molecule agonists of human RXFP1 can overcome this limitation and may provide a useful therapeutic approach, especially for chronic diseases such as heart failure and fibrosis. The first small-molecule agonists of RXFP1 were recently identified from a high-throughput screening, using a homogeneous cell based cAMP assay. Optimization of the hit compounds resulted in a series of highly potent and RXFP1 selective agonists with low cytotoxicity, and excellent in vitro ADME and pharmacokinetic properties. Here, we undertook extensive site directed mutagenesis studies in combination with computational modeling analysis to probe the molecular basis of the small-molecule binding to RXFP1. The results showed that the agonists bind to an allosteric site of RXFP1 in a manner that closely interacts with the seventh transmembrane domain (TM7) and the third extracellular loop (ECL3). Several residues were determined to play an important role in the agonist binding and receptor activation, including a hydrophobic region at TM7 consisting of W664, F668, and L670. The G659/T660 motif within ECL3 is crucial to the observed species selectivity of the agonists for RXFP1. The receptor binding and activation effects by the small molecule ML290 were compared with the cognate ligand, relaxin, providing valuable insights on the structural basis and molecular mechanism of receptor activation and selectivity for RXFP1. PMID- 26866461 TI - Sorazolons, Carbazole Alkaloids from Sorangium cellulosum Strain Soce375. AB - Sorazolons A (1) to E2 (9) were isolated from Sorangium cellulosum strain Soce375. Their molecular structures were elucidated using extensive HRESIMS and NMR analysis. The absolute configuration of sorazolon A (1) was determined by comparison of the experimental CD spectrum with quantum chemical calculated spectra for both enantiomers. Sorazolons D2 (7), E (8), and E2 (9) exhibit a moderate cytotoxic activity against mouse fibroblast cell line L929 with IC50 values between 5.0 MUM and 0.09 mM. PMID- 26866462 TI - Intrinsically Labeled Fluorescent Oligonucleotide Probes on Quantum Dots for Transduction of Nucleic Acid Hybridization. AB - Quantum dots (QDs) have been widely used in chemical and biosensing due to their unique photoelectrical properties and are well suited as donors in fluorescence resonance energy transfer (FRET). Selective hybridization interactions of oligonucleotides on QDs have been determined by FRET. Typically, the QD-FRET constructs have made use of labeled targets or have implemented labeled sandwich format assays to introduce dyes in proximity to the QDs for the FRET process. The intention of this new work is to explore a method to incorporate the acceptor dye into the probe molecule. Thiazole orange (TO) derivatives are fluorescent intercalating dyes that have been used for detection of double-stranded nucleic acids. One such dye system has been reported in which single-stranded oligonucleotide probes were doubly labeled with adjacent thiazole orange derivatives. In the absence of the fully complementary (FC) oligonucleotide target, the dyes form an H-aggregate, which results in quenching of fluorescence emission due to excitonic interactions between the dyes. The hybridization of the FC target to the probe provides for dissociation of the aggregate as the dyes intercalate into the double stranded duplex, resulting in increased fluorescence. This work reports investigation of the dependence of the ratiometric signal on the type of linkage used to conjugate the dyes to the probe, the location of the dye along the length of the probe, and the distance between adjacent dye molecules. The limit of detection for 34mer and 90mer targets was found to be identical and was 10 nM (2 pmol), similar to analogous QD-FRET using labeled oligonucleotide target. The detection system could discriminate a one base pair mismatch (1BPM) target and was functional without substantial compromise of the signal in 75% serum. The 1BPM was found to reduce background signal, indicating that the structure of the mismatch affected the environment of the intercalating dyes. PMID- 26866464 TI - Reaction Mechanism and Product Branching Ratios of the CH + C3H6 Reaction: A Theoretical Study. AB - The mechanism of CH(X(2)Pi) reaction with propene has been studied with ab initio CCSD(T)-F12/CBS//B3LYP/6-311G(d,p) calculations of the C4H7 potential energy surface and RRKM/master equation calculations of unimolecular rate constants for the various isomerization and dissociation steps available to the C4H7 radicals. Product branching ratios were calculated and were found to strongly depend on the initial chemically activated C4H7 complex formed in a barrierless entrance channel. If the reaction is initiated via either CH addition to the double bond in propene or CH insertions into the terminal sp(2) C-H or single C-C bonds, then 1,3-butadiene + H are predicted to be the dominant products, ethene + C2H3 radical are minor but non-negligible products, and a small amount of 1,2 butadiene + H is also produced. The reaction then proceeds through a key CH3CHCH(*)CH2 intermediate, which loses an H atom to form either 1,3- or 1,2 butadiene or isomerizes to (*)CH2CH2CHCH2 and then dissociates to ethene + C2H3 radical. If CH inserts into a C-H bond in the CH3 group the (*)CH2CH2CHCH2 complex is formed directly and then the major reaction products are predicted to be ethene + C2H3 radical and 1,3-butadiene + H. Finally, if CH inserts into the middle sp(2) C-H bond, a branched CH3C((*)CH2)CH2 complex is produced, which predominantly decomposes to allene + CH3 radical. A comparison of the calculated reaction mechanism with available experimental data indicates that the CH addition entrance channel is favorable, in which case the computed branching ratios are in agreement with the experimental result of Loison and Bergeat, who measured the H elimination branching ratio of 78 +/- 10%. However, the computed branching ratios quantitatively disagree with the experimental data by Trevitt et al., who observed a nearly 100% yield of the C4H6 + H products and also larger yields of 1,2-butadiene and 1-butyne than the calculations predict. The deviation of the theoretical results from experiment can be rationalized in terms of dynamical factors, which should favor direct dissociation of the CH3CHCH(*)CH2 precursor by H loss, especially to 1,2-butadiene, over its isomerization to (*)CH2CH2CHCH2 followed by the production of ethene + C2H3 radical, while 1 butyne might be formed through secondary H assisted isomerization of 1,2 butadiene. Overall, the calculations corroborate that the CH + C3H6 reaction could be a major source of 1,3-butadiene at low temperature and low pressure conditions in the interstellar medium and planetary atmospheres. PMID- 26866463 TI - Optimization and Analysis of Thermoelectric Properties of Unfilled Co(1-x y)Ni(x)Fe(y)Sb3 Synthesized via a Rapid Hydrothermal Procedure. AB - A series of nanostructured co-doped Co(1-x-y)Ni(x)Fe(y)Sb3 were fabricated using a rapid hydrothermal method at 170 degrees C for a duration of 12 h, followed by evacuated-and-encapsulated heating at 580 degrees C for a short period of 5 h. The resulting samples were characterized using powder X-ray diffraction, field emission scanning electron microscopy, bulk density, electronic and thermal transport measurements. The power factor of Co(1-x-y)Ni(x)Fe(y)Sb3 is significantly enhanced in the high-temperature region due to significant enhancement of the electrical conductivity and absolute value of thermopower. The latter arises from the onset of bipolar effect being shifted to higher temperatures as compared with the non-doped CoSb3. The room temperature thermal conductivity falls in the range between 1.22 and 1.67 W m(-1) K(-1) for Co(1-x y)Ni(x)Fe(y)Sb3. The thermal conductivity of both the (x,y) = (0.14,10) and (0.14,12) samples is measured up to 600 K and found to decrease with increasing temperature. The thermal conductivity of the (0.14,10) sample goes down to ~1.02 W m(-1) K(-1). As a result, zT = 0.68 is attained at 600 K. The lattice thermal conductivity is analyzed to gain insight into the contribution of various scattering processes that suppress the heat transfer through the phonons in Co(1 x-y)Ni(x)Fe(y)Sb3. The effect of the simultaneous presence of Co, Ni, and Fe elements on the electronic structure and transport properties of Co(1-x y)Ni(x)Fe(y)Sb3 is described using the quantum mechanical tunneling theory of electron transmission among the potential barriers. PMID- 26866465 TI - Glutamic Acid Selective Chemical Cleavage of Peptide Bonds. AB - Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis. PMID- 26866466 TI - Current Challenges and Prospective Research for Upscaling Hybrid Perovskite Photovoltaics. AB - Organic-inorganic hybrid perovskite photovoltaics (PSCs) are poised to push toward technology translation, but significant challenges complicating commercialization remain. Though J-V hysteresis and ecotoxicity are uniquely imposing issues at scale, CH3NH3PbI3 degradation is by far the sharpest limitation to the technology's potential market contribution. Herein, we offer a perspective on the practical market potential of PSCs, the nature of fundamental PSC challenges at scale, and an outline of prospective solutions for achieving module scale PSC production tailored to intrinsic advantages of CH3NH3PbI3. Although integrating PSCs into the energy grid is complicated by CH3NH3PbI3 degradation, the ability of PSCs to contribute to consumer electronics and other niche markets like those organic photovoltaics have sought footing in rests primarily upon the technology's price point. Thus, slot die, roll-to-roll processing has the greatest potential to enable PSC scale-up, and herein, we present a perspective on the research necessary to realize fully printable PSCs at scale. PMID- 26866467 TI - The killer immunoglobulin-like receptor KIR3DL1 in combination with HLA-Bw4 is protective against multiple sclerosis in African Americans. AB - We investigated the role of the KIR loci and their HLA class I ligands in a large cohort of African American multiple sclerosis (MS) patients (N=907) and controls (N=1456). No significant differences in carrier frequencies for any KIR locus or haplotype were observed between cases and controls. However, examination of KIR in the context of their cognate HLA ligands revealed a strong protective effect for KIR3DL1 in combination with HLA-A and -B alleles bearing the Bw4 motif (P=10( 8); odds ratio (OR)=0.60, confidence interval (CI)=0.50-0.71) and the Bw4 ligand alone (P<10(-6); OR=0.63, CI=0.53-0.75). The observed effect cannot be explained by either a specific HLA-B allele or by linkage disequilibrium with HLA-DRB1 or HLA-A. The protective effect was observed only in individuals who were not positive for the MS risk allele HLA-DRB1*15:01 (P<10(-6); OR=0.61, CI=0.51-0.74). Our study, the first investigation of KIR and MS in African Americans, confirms and refines previous findings in a European cohort. PMID- 26866468 TI - Two blinking mechanisms in highly confined AgInS2 and AgInS2/ZnS quantum dots evaluated by single particle spectroscopy. AB - Ternary AgInS2 quantum dots (QDs) have been found as promising cadmium-free, red shifted, and tunable luminescent bio-probes with efficient Stokes and anti-Stokes excitations and luminescence lifetimes (ca. 100 ns) convenient for time resolved techniques like fluorescence life-time imaging. Although the spectral properties of the AgInS2 QDs are encouraging, the complex recombination kinetics in the QDs being still far from understood, limits their full utility. In this paper we report on a model describing the recombination pathways responsible for large deviations from the first-order decay law observed commonly in the ternary chalcogenides. The presented results were evaluated by means of individual AgInS2 QD spectroscopy aided by first principles calculations including the electronic structure and structural reconstruction of the QDs. Special attention was devoted to study the impact of the surface charge state on the excited state relaxation and effect of its passivation by Zn(2+) ion alloying. Two different blinking mechanisms related to defect-assisted charge imbalance in the QD responsible for fast non-radiative relaxation of the excited states as well as surface recharging of the QD were found as the major causes of deviations from the first-order decay law. Careful optimization of the AgInS2 QDs would help to fabricate new red shifted and tunable fluorescent bio-probes characterized by low-toxicity, high quantum yield, long luminescence lifetime, and time stability, leading to many novel in vitro and in vivo applications based on fluorescence lifetime imaging (FLIM) and time-gated detection. PMID- 26866470 TI - Breathomics--exhaled volatile organic compound analysis to detect hepatic encephalopathy: a pilot study. AB - The current diagnostic challenge with diagnosing hepatic encephalopathy (HE) is identifying those with minimal HE as opposed to the more clinically apparent covert/overt HE. Rifaximin, is an effective therapy but earlier identification and treatment of HE could prevent liver disease progression and hospitalization. Our pilot study aimed to analyse breath samples of patients with different HE grades, and controls, using a portable electronic (e) nose. 42 patients were enrolled; 22 with HE and 20 controls. Bedside breath samples were captured and analysed using an uvFAIMS machine (portable e-nose). West Haven criteria applied and MELD scores calculated. We classify HE patients from controls with a sensitivity and specificity of 0.88 (0.73-0.95) and 0.68 (0.51-0.81) respectively, AUROC 0.84 (0.75-0.93). Minimal HE was distinguishable from covert/overt HE with sensitivity of 0.79 and specificity of 0.5, AUROC 0.71 (0.57 0.84). This pilot study has highlighted the potential of breathomics to identify VOCs signatures in HE patients for diagnostic purposes. Importantly this was performed utilizing a non-invasive, portable bedside device and holds potential for future early HE diagnosis. PMID- 26866469 TI - C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages. AB - There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis. PMID- 26866471 TI - Elevated Blood Lead Levels Are Associated with Reduced Risk of Malaria in Beninese Infants. AB - INTRODUCTION: Elevated blood lead levels (BLL) and malaria carry an important burden of disease in West Africa. Both diseases might cause anemia and they might entail long-term consequences for the development and the health status of the child. Albeit the significant impact of malaria on lead levels described in Nigeria, no evaluation of the effect of elevated BLL on malaria risk has been investigated so far. MATERIALS AND METHODS: Between 2010 and 2012, blood lead levels of 203 Beninese infants from Allada, a semi-rural area 50km North from Cotonou, were assessed at 12 months of age. To assess lead levels, blood samples were analyzed by mass spectrometry. In parallel, clinical, microbiological and hematological data were collected. More precisely, hemoglobin, serum ferritin, CRP, vitamin B12, folate levels, and Plasmodium falciparum parasitemia were assessed and stool samples were also analyzed. RESULTS: At 12 months, the mean BLL of infants was 7.41 MUg/dL (CI: 65.2; 83), and 128 infants (63%) had elevated blood lead levels, defined by the CDC as BLL>5 MUg/dL. Lead poisoning, defined as BLL>10 MUg/dL, was found in 39 infants (19%). Twenty-five infants (12.5%) had a positive blood smear at 12 months and 144 infants were anemic (71%, hemoglobin<110 g/L). Elevated blood lead levels were significantly associated with reduced risk of a positive blood smear (AOR = 0.38, P-value = 0.048) and P. falciparum parasite density (beta-estimate = -1.42, P-value = 0.03) in logistic and negative binomial regression multivariate models, respectively, adjusted on clinical and environmental indicators. CONCLUSION: Our study shows for the first time that BLL are negatively associated with malarial risk considering other risk factors. Malaria is one of the main causes of morbidity and mortality in infants under 5 years worldwide, and lead poisoning is the 6th most important contributor to the global burden of diseases measured in disability adjusted life years (DALYs) according to the Institute of Health Metrics. In conclusion, due to the high prevalence of elevated BLL, health interventions should look forward to minimize the exposure to lead to better protect the population in West Africa. PMID- 26866472 TI - 30-Day Mortality in Acute Pulmonary Embolism: Prognostic Value of Clinical Scores and Anamnestic Features. AB - PURPOSE: Identification of high-risk patients with pulmonary embolism is vital. The aim of the present study was to examine clinical scores, their single items, and anamnestic features in their ability to predict 30-day mortality. MATERIALS AND METHODS: A retrospective, single-center study from 06/2005 to 01/2010 was performed. Inclusion criteria were presence of pulmonary embolism, availability of patient records and 30-day follow-up. The following clinical scores were calculated: Acute Physiology and Chronic Health Evaluation II, original and simplified pulmonary embolism severity index, Glasgow Coma Scale, and euroSCORE II. RESULTS: In the study group of 365 patients 39 patients (10.7%) died within 30 days due to pulmonary embolism. From all examined scores and parameters the best predictor of 30-day mortality were the Glasgow Coma scale (<= 10) and parameters of the circulatory system including presence of mechanical ventilation, arterial pH (< 7.335), and systolic blood pressure (< 99 mm Hg). CONCLUSIONS: Easy to ascertain circulatory parameters have the same or higher prognostic value than the clinical scores that were applied in this study. From all clinical scores studied the Glasgow Coma Scale was the most time- and cost efficient one. PMID- 26866474 TI - Recent Land Use Change to Agriculture in the U.S. Lake States: Impacts on Cellulosic Biomass Potential and Natural Lands. AB - Perennial cellulosic feedstocks may have potential to reduce life-cycle greenhouse gas (GHG) emissions by offsetting fossil fuels. However, this potential depends on meeting a number of important criteria involving land cover change, including avoiding displacement of agricultural production, not reducing uncultivated natural lands that provide biodiversity habitat and other valued ecosystem services, and avoiding the carbon debt (the amount of time needed to repay the initial carbon loss) that accompanies displacing natural lands. It is unclear whether recent agricultural expansion in the United States competes with lands potentially suited for bioenergy feedstocks. Here, we evaluate how recent land cover change (2008-2013) has affected the availability of lands potentially suited for bioenergy feedstock production in the U.S. Lake States (Minnesota, Wisconsin, Michigan) and its impact on other natural ecosystems. The region is potentially well suited for a diversity of bioenergy production systems, both grasses and woody biomass, due to the widespread forest economy in the north and agricultural economy in the south. Based on remotely-sensed data, our results show that between 2008 and 2013, 836,000 ha of non-agricultural open lands were already converted to agricultural uses in the Lake States, a loss of nearly 37%. The greatest relative changes occurred in the southern half that includes some of the most diverse cultivable lands in the country. We use transition diagrams to reveal gross changes that can be obscured if only net change is considered. Our results indicate that expansion of row crops (corn, soybean) was responsible for the majority of open land loss. Even if recently lost open lands were brought into perennial feedstock production, there would a substantial carbon debt. This reduction in open land availability for biomass production is closing the window of opportunity to establish a sustainable cellulosic feedstock economy in the Lake States as mandated by current Federal policy, incurring a substantial GHG debt, and displacing a range of other natural ecosystems and their services. PMID- 26866473 TI - Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease. AB - AIMS: Oxidative stress is central to the pathogenesis of Parkinson's disease (PD), but the mechanisms involved in the control of this stress in dopaminergic cells are not fully understood. There is increasing evidence that selenoproteins play a central role in the control of redox homeostasis and cell defense, but the precise contribution of members of this family of proteins during the course of neurodegenerative diseases is still elusive. RESULTS: We demonstrated first that selenoprotein T (SelT) whose gene disruption is lethal during embryogenesis, exerts a potent oxidoreductase activity. In the SH-SY5Y cell model of dopaminergic neurons, both silencing and overexpression of SelT affected oxidative stress and cell survival. Treatment with PD-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone triggered SelT expression in the nigrostriatal pathway of wild-type mice, but provoked rapid and severe parkinsonian-like motor defects in conditional brain SelT-deficient mice. This motor impairment was associated with marked oxidative stress and neurodegeneration and decreased tyrosine hydroxylase activity and dopamine levels in the nigrostriatal system. Finally, in PD patients, we report that SelT is tremendously increased in the caudate putamen tissue. INNOVATION: These results reveal the activity of a novel selenoprotein enzyme that protects dopaminergic neurons against oxidative stress and prevents early and severe movement impairment in animal models of PD. CONCLUSIONS: Our findings indicate that selenoproteins such as SelT play a crucial role in the protection of dopaminergic neurons against oxidative stress and cell death, providing insight into the molecular underpinnings of this stress in PD. PMID- 26866476 TI - Posttraumatic growth and perceived health: The role of posttraumatic stress symptoms. AB - The contested discourse regarding the nature of posttraumatic growth (PTG) includes 2 main competitive claims. The first argues that PTG reflects authentic positive transformation while the second posits that PTG reflects illusory defenses that could be maladaptive in the long run. The present study assesses these competing claims by investigating secondary PTG in relation to the somatic domain. Specifically, this study investigates: (a) the association between PTG, and perceived health (PH), as measured by 3 indices of somatic complaints, self rated health (SRH) and a number of health problems; (b) the association between PTG, posttraumatic stress symptoms (PTSS) and PH over time; and (c) the mediating role of PTSS between PTG and PH, among wives of former prisoners of war (ex-POWs) and wives of control veterans. Assessments were conducted 30 (T1) and 38 (T2) years after the Yom Kippur War. Results showed that wives of ex-POWs endorsed higher PTSS, higher PTG and poorer PH, compared to control wives. Higher PTG was associated with higher PTSS and poorer PH. PTG at T1 predicted an increase in PTSS between T1 and T2, which in turn was correlated with poorer PH. PTSS at T2 as well as changes in PTSS from T1 to T2 mediated the association between T1 PTG and T2 PH measures. The present findings imply that PTG might have negative implications on PH through the amplification of PTSS, among secondary trauma victims. It seems that although spouses of trauma victims describe benefits resulting from vicarious trauma exposures, their body indicates differently. (PsycINFO Database Record PMID- 26866475 TI - Magnetic Resonance Imaging after Completion of Neoadjuvant Chemotherapy Can Accurately Discriminate between No Residual Carcinoma and Residual Ductal Carcinoma In Situ in Patients with Triple-Negative Breast Cancer. AB - BACKGROUND: The accurate evaluation of favorable response to neoadjuvant chemotherapy (NCT) is critical to determine the extent of surgery. We investigated independent clinicopathological and radiological predictors to discriminate no residual carcinoma (ypT0) from residual ductal carcinoma in situ (ypTis) in breast cancer patients who received NCT. PATIENTS AND METHODS: Parameters of 117 patients attaining pathological complete response (CR) in the breast after NCT between January 2010 and December 2013 were retrospectively evaluated by univariate and multivariate analyses. All patients underwent mammography, ultrasound, and magnetic resonance imaging (MRI) before and after NCT. RESULTS: There were 67 (57.3%) patients with ypT0. These patients were associated with hormone receptor-negative status, human epidermal growth factor receptor-2 (HER2)-negative tumors, and a higher likelihood of breast-conservation surgery. Baseline mammographic and MRI presentation of the main lesion, absence of associated microcalcifications, shape, posterior features, and absence of calcifications on ultrasound were significantly associated with ypT0. CR in mammography, ultrasound, or MRI after NCT was also related to ypT0. By multivariate analysis, independent predictors of ypT0 were the triple-negative subtype [Odds ratio (OR), 4.23; 95% confidence interval (CI), 1.11-16.09] and CR in MRI after NCT (OR, 5.23; 95% CI, 1.53-17.85). Stratified analysis by breast cancer subtype demonstrated that MRI well predicted ypT0 in all subtypes except the HER2-positive subtype. In particular, of 40 triple-negative subtypes, 22 showed CR in MRI and 21 (95.5%) were ypT0 after NCT. CONCLUSION: Among imaging modalities, breast MRI can potentially distinguish between ypT0 and ypTis after NCT, especially in patients with triple-negative breast cancer. This information can help clinicians evaluate tumor response to NCT and plan surgery for breast cancer patients of all subtypes except for those with HER2-enriched tumors after NCT. PMID- 26866477 TI - Ethnic differences in problem perception: Immigrant mothers in a parenting intervention to reduce disruptive child behavior. AB - Ethnic minority families in Europe are underrepresented in mental health care-a profound problem for clinicians and policymakers. One reason for their underrepresentation seems that, on average, ethnic minority families tend to perceive externalizing and internalizing child behavior as less problematic. There is concern that this difference in problem perception might limit intervention effectiveness. We tested the extent to which ethnic differences in problem perception exist when ethnic minority families engage in mental health service and whether lower levels of problem perception diminish parenting intervention effects to reduce disruptive child behavior. Our sample included 136 mothers of 3- to 8-year-olds (35% female) from the 3 largest ethnic groups in the Netherlands (43% Dutch; 35% Moroccan; 22% Turkish). Mothers reported on their child's externalizing and internalizing behavior and their perception of this behavior as problematic. They were then randomly assigned to the Incredible Years parenting intervention or a wait list control condition. We contrasted maternal reports of problem perception to teacher reports of the same children. Moroccan and Turkish mothers, compared with Dutch mothers, perceived similar levels of child behavior problems as less problematic, and as causing less impairment and burden. Teacher problem perception did not vary across children from different ethnic groups. Importantly, maternal problem perception did not affect parenting intervention effectiveness to reduce disruptive child behavior. Our findings suggest that ethnic differences in problem perception exist once families engage in treatment, but that lower levels of problem perception do not diminish treatment effects. (PsycINFO Database Record PMID- 26866478 TI - Origin and Evolution of Rickettsial Plasmids. AB - BACKGROUND: Rickettsia species are strictly intracellular bacteria that have undergone a reductive genomic evolution. Despite their allopatric lifestyle, almost half of the 26 currently validated Rickettsia species have plasmids. In order to study the origin, evolutionary history and putative roles of rickettsial plasmids, we investigated the evolutionary processes that have shaped 20 plasmids belonging to 11 species, using comparative genomics and phylogenetic analysis between rickettsial, microbial and non-microbial genomes. RESULTS: Plasmids were differentially present among Rickettsia species. The 11 species had 1 to 4 plasmid (s) with a size ranging from 12 kb to 83 kb. We reconstructed pRICO, the last common ancestor of the current rickettsial plasmids. pRICO was vertically inherited mainly from Rickettsia/Orientia chromosomes and diverged vertically into a single or multiple plasmid(s) in each species. These plasmids also underwent a reductive evolution by progressive gene loss, similar to that observed in rickettsial chromosomes, possibly leading to cryptic plasmids or complete plasmid loss. Moreover, rickettsial plasmids exhibited ORFans, recent gene duplications and evidence of horizontal gene transfer events with rickettsial and non-rickettsial genomes mainly from the alpha/gamma proteobacteria lineages. Genes related to maintenance and plasticity of plasmids, and to adaptation and resistance to stress mostly evolved under vertical and/or horizontal processes. Those involved in nucleotide/carbohydrate transport and metabolism were under the influence of vertical evolution only, whereas genes involved in cell wall/membrane/envelope biogenesis, cycle control, amino acid/lipid/coenzyme and secondary metabolites biosynthesis, transport and metabolism underwent mainly horizontal transfer events. CONCLUSION: Rickettsial plasmids had a complex evolution, starting with a vertical inheritance followed by a reductive evolution associated with increased complexity via horizontal gene transfer as well as gene duplication and genesis. The plasmids are plastic and mosaic structures that may play biological roles similar to or distinct from their co-residing chromosomes in an obligate intracellular lifestyle. PMID- 26866480 TI - Considering Future Potential Regarding Structural Diversity in Selection of Forest Reserves. AB - A rich structural diversity in forests promotes biodiversity. Forests are dynamic and therefore it is crucial to consider future structural potential when selecting reserves, to make robust conservation decisions. We analyzed forests in boreal Sweden based on 17,599 National Forest Inventory (NFI) plots with the main aim to understand how effectiveness of reserves depends on the time dimension in the selection process, specifically by considering future structural diversity. In the study both the economic value and future values of 15 structural variables were simulated during a 100 year period. To get a net present structural value (NPSV), a single value covering both current and future values, we used four discounting alternatives: (1) only considering present values, (2) giving equal importance to values in each of the 100 years within the planning horizon, (3) applying an annual discount rate considering the risk that values could be lost, and (4) only considering the values in year 100. The four alternatives were evaluated in a reserve selection model under budget-constrained and area constrained selections. When selecting young forests higher structural richness could be reached at a quarter of the cost over almost twice the area in a budget constrained selection compared to an area-constrained selection. Our results point to the importance of considering future structural diversity in the selection of forest reserves and not as is done currently to base the selection on existing values. Targeting future values increases structural diversity and implies a relatively lower cost. Further, our results show that a re-orientation from old to young forests would imply savings while offering a more extensive reserve network with high structural qualities in the future. However, caution must be raised against a drastic reorientation of the current old-forest strategy since remnants of ancient forests will need to be prioritized due to their role for disturbance-sensitive species. PMID- 26866479 TI - Inferring Growth Control Mechanisms in Growing Multi-cellular Spheroids of NSCLC Cells from Spatial-Temporal Image Data. AB - We develop a quantitative single cell-based mathematical model for multi-cellular tumor spheroids (MCTS) of SK-MES-1 cells, a non-small cell lung cancer (NSCLC) cell line, growing under various nutrient conditions: we confront the simulations performed with this model with data on the growth kinetics and spatial labeling patterns for cell proliferation, extracellular matrix (ECM), cell distribution and cell death. We start with a simple model capturing part of the experimental observations. We then show, by performing a sensitivity analysis at each development stage of the model that its complexity needs to be stepwise increased to account for further experimental growth conditions. We thus ultimately arrive at a model that mimics the MCTS growth under multiple conditions to a great extent. Interestingly, the final model, is a minimal model capable of explaining all data simultaneously in the sense, that the number of mechanisms it contains is sufficient to explain the data and missing out any of its mechanisms did not permit fit between all data and the model within physiological parameter ranges. Nevertheless, compared to earlier models it is quite complex i.e., it includes a wide range of mechanisms discussed in biological literature. In this model, the cells lacking oxygen switch from aerobe to anaerobe glycolysis and produce lactate. Too high concentrations of lactate or too low concentrations of ATP promote cell death. Only if the extracellular matrix density overcomes a certain threshold, cells are able to enter the cell cycle. Dying cells produce a diffusive growth inhibitor. Missing out the spatial information would not permit to infer the mechanisms at work. Our findings suggest that this iterative data integration together with intermediate model sensitivity analysis at each model development stage, provide a promising strategy to infer predictive yet minimal (in the above sense) quantitative models of tumor growth, as prospectively of other tissue organization processes. Importantly, calibrating the model with two nutriment-rich growth conditions, the outcome for two nutriment-poor growth conditions could be predicted. As the final model is however quite complex, incorporating many mechanisms, space, time, and stochastic processes, parameter identification is a challenge. This calls for more efficient strategies of imaging and image analysis, as well as of parameter identification in stochastic agent-based simulations. PMID- 26866481 TI - Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders. AB - Respiratory viruses are a cause of upper respiratory tract infections (URTI), but can be associated with severe lower respiratory tract infections (LRTI) in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV) and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17%) were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111) underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic). LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1)pdm09, A(H3N2), influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75%) of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01) and was most pronounced in patients with RSV infection (n = 16) with a median duration of viral shedding for 80 days (range 35-334 days). Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for efficient infection control in immunocompromised patients. PMID- 26866482 TI - Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. METHODS: One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (?Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. RESULTS: Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and ?Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and ?Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. CONCLUSIONS: The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD. PMID- 26866483 TI - Genotypic Diversity of Staphylococcus aureus alpha-Hemolysin Gene (hla) and Its Association with Clonal Background: Implications for Vaccine Development. AB - The alpha-hemolysin, encoded by the hla gene, is a major virulence factor in S. aureus infections. Changes in key amino acid residues of alpha-hemolysin can result in reduction, or even loss, of toxicity. The aim of this study was to investigate the diversity of the hla gene sequence and the relationship of hla variants to the clonal background of S. aureus isolates. A total of 47 clinical isolates from China were used in this study, supplemented with in silico analysis of 318 well-characterized whole genome sequences from globally distributed isolates. A total of 28 hla genotypes were found, including three unique to isolates from China, 20 found only in the global genomes and five found in both. The hla genotype generally correlated with the clonal background, particularly the multilocus sequence type, but was not related to geographic origin, host source or methicillin-resistance phenotype. In addition, the hla gene showed greater diversity than the seven loci utilized in the MLST scheme for S. aureus. Our investigation has provided genetic data which may be useful for future studies of toxicity, immunogenicity and vaccine development. PMID- 26866484 TI - Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India. AB - OBJECTIVES: The present study was undertaken to investigate the mutations that are present in mexR gene of multidrug resistant (MDR) isolates of Pseudomonas aeruginosa collected from a tertiary referral hospital of north east India. METHODS: 76 MDR clinical isolates of P. aeruginosa were obtained from the patients who were admitted to or attended the clinics of Silchar medical college and hospital. They were screened phenotypically for the presence of efflux pump activity by an inhibitor based method. Acquired resistance mechanisms were detected by multiplex PCR. Real time PCR was performed to study the expression of mexA gene of MexAB-OprM efflux pump in isolates with increase efflux pump activity. mexR gene of the isolates with overexpressed MexAB-OprM efflux pump was amplified, sequenced and analysed. RESULTS: Out of 76 MDR isolates, 24 were found to exhibit efflux pump activity phenotypically against ciprofloxacin and meropenem. Acquired resistance mechanisms were absent in 11 of them and among those isolates, 8 of them overexpressed MexAB-OprM. All the 8 isolates possessed mutation in mexR gene. 11 transversions, 4 transitions, 2 deletion mutations and 2 insertion mutations were found in all the isolates. However, the most significant observation was the formation of a termination codon at 35th position which resulted in the termination of the polypeptide and leads to overexpression of the MexAB-OprM efflux pump. CONCLUSIONS: This study highlighted emergence of a novel mutation which is probably associated with multi drug resistance. Therefore, further investigations and actions are needed to prevent or at least hold back the expansion and emergence of newer mutations in nosocomial pathogens which may compromise future treatment options. PMID- 26866485 TI - Interim Guidelines for Prevention of Sexual Transmission of Zika Virus - United States, 2016. AB - Zika virus is a mosquito-borne flavivirus primarily transmitted by Aedes aegypti mosquitoes (1,2). Infection with Zika virus is asymptomatic in an estimated 80% of cases (2,3), and when Zika virus does cause illness, symptoms are generally mild and self-limited. Recent evidence suggests a possible association between maternal Zika virus infection and adverse fetal outcomes, such as congenital microcephaly (4,5), as well as a possible association with Guillain-Barre syndrome. Currently, no vaccine or medication exists to prevent or treat Zika virus infection. Persons residing in or traveling to areas of active Zika virus transmission should take steps to prevent Zika virus infection through prevention of mosquito bites (http://www.cdc.gov/zika/prevention/). PMID- 26866486 TI - G = E: What GWAS Can Tell Us about the Environment. AB - As our understanding of genetics has improved, genome-wide association studies (GWAS) have identified numerous variants associated with lifestyle behaviours and health outcomes. However, what is sometimes overlooked is the possibility that genetic variants identified in GWAS of disease might reflect the effect of modifiable risk factors as well as direct genetic effects. We discuss this possibility with illustrative examples from tobacco and alcohol research, in which genetic variants that predict behavioural phenotypes have been seen in GWAS of diseases known to be causally related to these behaviours. This consideration has implications for the interpretation of GWAS findings. PMID- 26866488 TI - Bahman Jabbari, MD. PMID- 26866489 TI - Botulinum Toxin Treatment in Neurology. PMID- 26866487 TI - Progress in methods for rare variant association. AB - Empirical studies and evolutionary theory support a role for rare variants in the etiology of complex traits. Given this motivation and increasing affordability of whole-exome and whole-genome sequencing, methods for rare variant association have been an active area of research for the past decade. Here, we provide a survey of the current literature and developments from the Genetics Analysis Workshop 19 (GAW19) Collapsing Rare Variants working group. In particular, we present the generalized linear regression framework and associated score statistic for the 2 major types of methods: burden and variance components methods. We further show that by simply modifying weights within these frameworks we arrive at many of the popular existing methods, for example, the cohort allelic sums test and sequence kernel association test. Meta-analysis techniques are also described. Next, we describe the 6 contributions from the GAW19 Collapsing Rare Variants working group. These included development of new methods, such as a retrospective likelihood for family data, a method using genomic structure to compare cases and controls, a haplotype-based meta-analysis, and a permutation-based method for combining different statistical tests. In addition, one contribution compared a mega-analysis of family-based and population-based data to meta-analysis. Finally, the power of existing family based methods for binary traits was compared. We conclude with suggestions for open research questions. PMID- 26866490 TI - Botulinum Toxin to Treat Neurogenic Bladder. AB - Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data. PMID- 26866491 TI - The Botulinum Toxin as a Therapeutic Agent: Molecular Structure and Mechanism of Action in Motor and Sensory Systems. AB - Botulinum neurotoxin (BoNT) produced by Clostridium botulinum is the most potent molecule known to mankind. Higher potency of BoNT is attributed to several factors, including structural and functional uniqueness, target specificity, and longevity. Although BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity. Weakening of muscles due to peripheral action of BoNT produces a therapeutic effect. Depending on the target tissue, BoNT can block the cholinergic neuromuscular or cholinergic autonomic innervation of exocrine glands and smooth muscles. In recent observations of the analgesic properties of BoNT, the toxin modifies the sensory feedback loop to the central nervous system. Differential effects of BoNT in excitatory and inhibitory neurons provide a unique therapeutic tool. In this review the authors briefly summarize the structure and mechanism of actions of BoNT on motor and sensory neurons to explain its therapeutic effects and future potential. PMID- 26866492 TI - Botulinum Toxin Treatment of Autonomic Disorders: Focal Hyperhidrosis and Sialorrhea. AB - Primary focal hyperhidrosis is a common autonomic disorder that significantly impacts quality of life. It is characterized by excessive sweating confined to circumscribed areas, such as the axillae, palms, soles, and face. Less frequent types of focal hyperhidrosis secondary to underlying causes include gustatory sweating in Frey's syndrome and compensatory sweating in Ross' syndrome and after sympathectomy. Approval of onabotulinumtoxinA for severe primary axillary hyperhidrosis in 2004 has revolutionized the treatment of this indication. Meanwhile further type A botulinum neurotoxins like abobotulinumtoxinA and incobotulinumtoxinA, as well as the type B botulinum neurotoxin rimabotulinumtoxinB are successfully used off-label for axillary and various other types of focal hyperhidrosis. For unexplained reasons, the duration of effect differs considerably at different sites. Beside hyperhidrosis, botulinum neurotoxin is also highly valued for the treatment of sialorrhea affecting patients with Parkinson's disease, cerebral palsy, amyotrophic lateral sclerosis, motor neuron disease, and other neurologic conditions. With correct dosing and application, side effects are manageable and transient. PMID- 26866493 TI - Botulinum Toxin: Preparations for Clinical Use, Immunogenicity, Side Effects, and Safety Profile. AB - Botulinum toxin (BoNT) formulations are being used for a variety of medical applications. The use of BoNT preparations is continuously expanding with new formulations and indications. Of the seven antigenically distinct BoNTs, only two serotypes, type A and type B are commonly available for therapeutic use. The four available BoNT products are not equivalent and the knowledge of their formulations is crucial for product selection, avoidance of medication errors, therapeutic efficacy and safety. Generally, BoNT injection is a safe procedure when administered by an experienced injector. Side effects are always transient, and in the majority of cases they are mild and tolerable. PMID- 26866494 TI - Voiding Dysfunction in Multiple Sclerosis. AB - Voiding dysfunction is a common and debilitating consequence of multiple sclerosis (MS). The prevalence and severity of voiding dysfunction increases with the increasing severity of MS, but even the mildest forms of the disease are associated with urinary symptoms in 30% of patients. Every component of the central nervous system is involved in regulating voiding; as a result, MS can lead to a wide variety of urinary symptoms and urologic complications. The effect of MS on voiding can be classified according to the resulting function of the bladder and the urethral sphincter during storage and emptying of urine. Therapy is targeted to the specific bladder and sphincter abnormalities that occur. The primary goals of therapy are prevention of injury to the upper urinary tract (kidneys), reduction in urinary tract infections, and maintenance of urinary continence. These goals can be achieved by interventions ranging from behavioral modification to major reconstructive surgery. PMID- 26866495 TI - Update on the Use of Botulinum Toxin Therapy for Focal and Task-Specific Dystonias. AB - Focal dystonia is defined by anatomical distribution and represents a distinct entity from generalized dystonia. Task-specific dystonia occurs in the context of specific patterns of movement. Botulinum neurotoxin (BoNT) injections are the treatment of choice in most cases. Several formulations are available; the approved indications, dosing, and some administration details, differ between them. The major forms of focal and task-specific dystonia are reviewed, along with the evidence for BoNT therapy, the expected benefit and side effects, and practical points guiding the injections. PMID- 26866496 TI - Botulinum Toxin Treatment of Cervical Dystonia. AB - The use of botulinum toxin for the treatment of cervical dystonia (CD) was first reported in 1985. Since then, four commercially available formulations have been approved by the U.S. Food and Drug Administration for use in CD, including three botulinum toxin A formulations and one botulinum toxin B formulation. Recent clinical trials have generally demonstrated good efficacy and tolerability. Commonly reported side effects include dysphagia, muscle weakness, and dry mouth. Secondary nonresponse may develop, but the relationship of detected antibodies to clinical responsiveness remains unclear. Further research is needed into the treatment of complex subtypes of CD and the potential use of alternate botulinum toxin serotypes or subtypes with less immunogenic profiles. PMID- 26866497 TI - Botulinum Toxin for the Treatment of Tremor and Tics. AB - The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the U.S. Food and Drug Administration for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and nonneurologic disorders. Despite a paucity of randomized controlled trials, BoNT has been found to be beneficial in treating a variety of tremors and tics when used by clinicians skilled in the administration of the drug for these hyperkinetic movement disorders. Botulinum toxin injections can provide meaningful improvement in patients with localized tremors and tics; in some cases, they may be an alternative to other treatments with more undesirable adverse effects. PMID- 26866498 TI - Botulinum Toxin Treatment of Spasticity in Adults and Children. AB - Spasticity is a frequent symptom in stroke, multiple sclerosis, cerebral or spinal trauma, and cerebral palsy that affects and disables a large number of adults and children. In this review, we discuss the pathophysiology and nonpharmacologic and pharmacologic treatments of spasticity with emphasis on the role of botulinum neurotoxins (BoNTs). The world literature is reviewed on double blind and placebo-controlled clinical trials reporting safety and efficacy of BoNT treatment in adult spasticity and spasticity of children with cerebral palsy. The evidence for efficacy is presented from recommendations of the Assessment and Therapeutics subcommittee of the American Academy of Neurology. A technical section describes the techniques and recommended doses of BoNTs in spasticity. PMID- 26866499 TI - Botulinum Toxin Treatment of Neuropathic Pain. AB - Neuropathic pain (NP), a common form of human pain, often poorly responds to analgesic medications. In this review the authors discuss the pathophysiology and conventional treatment of neuropathic pain and provide evidenced-based statements on the efficacy of botulinum neurotoxins (BoNTs) in this form of pain. The level of efficacy for BoNT treatment in each category of NP is defined according to the published guidelines of the American Academy of Neurology. The data indicate that BoNT treatment (most of the literature is with onabotulinumtoxinA) is effective (level A evidence) in postherpetic neuralgia and trigeminal neuralgia. It is probably effective (level B) in posttraumatic neuralgia and painful diabetic neuropathy. The data on complex regional pain syndrome, carpal tunnel syndrome, occipital neuralgia, and phantom limb pain are preliminary and await conduction of randomized, blinded clinical trials. Much remains to be learned about the most effective dosage and technique of injection, optimum dilutions, and differences among BoNTs in the treatment of neuropathic pain. PMID- 26866500 TI - Botulinum Toxin Treatment of Blepharospasm, Orofacial/Oromandibular Dystonia, and Hemifacial Spasm. AB - Blepharospasm is a focal dystonia characterized by involuntary, repetitive eye closure. Orofacial and oromandibular dystonia describe involuntary dystonic movements of orofacial and oromandibular musculature. Hemifacial spasm is characterized by repetitive synchronous contraction of facial nerve innervated muscles on one side of the face. In this article, the clinical presentation, epidemiology, and approaches to treatment are reviewed. Technical aspects of using botulinum toxin for treatment and reported outcomes are discussed. PMID- 26866501 TI - The Use of Botulinum Toxin in the Management of Headache Disorders. AB - Headache disorders can be further classified as episodic (< 15 headache days per month) or chronic (>= 15 headache days per month for more than 3 months). Chronic migraine (CM) requires that headaches occur on 15 or more days a month for more than 3 months. These headaches must be migraines on at least 8 days per month. There are seven botulinum toxin (BoNT) serotypes (A1, A2, A3, B, C1, D, E, F, and G). All serotypes inhibit acetylcholine release, although their intracellular target proteins, physiochemical characteristics, and potencies are different. Its mechanism of action in pain is being investigated. Botulinum toxin type A (BoNT A) has been the most widely studied serotype for therapeutic purposes. A major clinical advantage of type A toxin arises from its prolonged duration of action due to the longevity of its protease (90 days in rats and probably much longer in human neurons). Clinical studies suggest that BoNT is a safe treatment and is efficacious for the prevention of some forms of migraine, such as CM, and perhaps high-frequency episodic migraine. PMID- 26866502 TI - Overcoming Strain-Induced Rearrangement Reactions: A Mild Dehydrative Aromatization Protocol for Synthesis of Highly Distorted p-Phenylenes. AB - A series of p-terphenyl-based macrocycles, containing highly distorted p phenylene units, have been synthesized. Biaryl bonds of the nonplanar p-terphenyl nuclei were constructed in the absence of Pd-catalyzed or Ni-mediated cross coupling reactions, using 1,4-diketones as surrogates to strained arene units. A streamlined synthetic protocol for the synthesis of 1,4-diketo macrocycles has been developed, using only 2.5 mol % of the Hoveyda-Grubbs second-generation catalyst in both metathesis and transfer hydrogenation reactions. Under protic acid-mediated dehydrative aromatization conditions, the central and most strained benzene ring of the p-terphenyl systems was susceptible to rearrangement reactions. To overcome this, a dehydrative aromatization protocol using the Burgess reagent was developed. Under these conditions, no strain-induced rearrangement reactions occur, delivering p-phenylene units with up to 28.4 kcal/mol strain energy and deformation angles that sum up to 40 degrees . PMID- 26866503 TI - Population-Based Evidence that Survival in Amyotrophic Lateral Sclerosis is Related to Weight Loss at Diagnosis. AB - BACKGROUND/AIMS: In a population-based setting, we aimed to (i) describe weight loss (WL) of amyotrophic lateral sclerosis (ALS) patients at the time of diagnosis and (ii) evaluate the association between WL and survival. METHODS: All patients recruited in the FRALim register (2000-2013) were considered to be included in this study. Time-to-death analyses were performed using a multivariable Cox model. Model discrimination and calibration were assessed. RESULTS: Among 322 patients in the register, 261 (81%) were included. At the time of diagnosis, 50.6% of patients reported a WL of more than 5%: 14.6% with WL between 5 and 10% and 36.0% with a WL of more than 10%. WL was independently associated with survival (p = 0.002). Patients with a WL of 10% or more experienced a 45% increase in the risk of death (95% CI 6-99) with respect to patients with a WL lower than 5% or no WL. The introduction of WL significantly improved the model's discrimination achieving a survival C statistic of 79.5% (95% CI 75.6-83.5, p = 0.006) at 12 months. CONCLUSION: More than 50% of ALS patients experience a WL of more than 5% at the time of diagnosis. This finding highlights the need for randomized trials to evaluate the effect of nutritional interventions to improve ALS survival. PMID- 26866504 TI - Platelet-to-Lymphocyte Ratio Improves the Predictive Power of GRACE Risk Score for Long-Term Cardiovascular Events in Patients with Acute Coronary Syndrome. AB - OBJECTIVES: This study aims to evaluate the relationship between platelet-to lymphocyte ratio (PLR) and GRACE risk score and to examine whether PLR on admission can improve the predictive value of GRACE risk score for cardiovascular disease (CVD) events in patients with acute coronary syndrome (ACS). METHODS: PLR was calculated from the platelet and lymphocyte counts from the complete blood count of 2,230 ACS patients upon admission. The GRACE risk score was also calculated. RESULTS: Spearman's rank correlation demonstrated that GRACE risk score was positively correlated with PLR (r = 0.190, p < 0.001). After a median follow-up period of 58 months, multivariate Cox analysis showed that both GRACE risk score [hazard ratio (HR) 1.092, 95% confidence interval (CI) 1.067-1.117, p < 0.001] and PLR (HR 1.100, 95% CI 1.088-1.112, p < 0.001) could independently predict CVD events. Receiver-operating characteristic curve (ROC) analysis proved that using PLR together with GRACE risk score improved the score from 0.70 (95% CI 0.67-0.73, p < 0.001) when used alone to 0.81 (95% CI 0.79-0.83, p < 0.001) for CVD events and from 0.73 (95% CI 0.70-0.77, p < 0.001) when used alone to 0.80 (95% CI 0.77-0.83, p < 0.001) for all-cause mortality. CONCLUSIONS: This study proves, for the first time, a positive association between GRACE risk score and PLR, and that a combination of PLR and GRACE risk score is more effective in predicting CVD events in ACS patients. PMID- 26866505 TI - Multifrequency spectrum analysis using fully digital G Mode-Kelvin probe force microscopy. AB - Since its inception over two decades ago, Kelvin probe force microscopy (KPFM) has become the standard technique for characterizing electrostatic, electrochemical and electronic properties at the nanoscale. In this work, we present a purely digital, software-based approach to KPFM utilizing big data acquisition and analysis methods. General mode (G-Mode) KPFM works by capturing the entire photodetector data stream, typically at the sampling rate limit, followed by subsequent de-noising, analysis and compression of the cantilever response. We demonstrate that the G-Mode approach allows simultaneous multi harmonic detection, combined with on-the-fly transfer function correction required for quantitative CPD mapping. The KPFM approach outlined in this work significantly simplifies the technique by avoiding cumbersome instrumentation optimization steps (i.e. lock in parameters, feedback gains etc), while also retaining the flexibility to be implemented on any atomic force microscopy platform. We demonstrate the added advantages of G-Mode KPFM by allowing simultaneous mapping of CPD and capacitance gradient (C') channels as well as increased flexibility in data exploration across frequency, time, space, and noise domains. G-Mode KPFM is particularly suitable for characterizing voltage sensitive materials or for operation in conductive electrolytes, and will be useful for probing electrodynamics in photovoltaics, liquids and ionic conductors. PMID- 26866506 TI - Brief Report: Intensification to Triple Therapy After Treatment With Nonbiologic Disease-Modifying Antirheumatic Drugs for Rheumatoid Arthritis in the United States From 2009 to 2014. AB - OBJECTIVE: Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (DMARDs) have similar efficacy in patients with rheumatoid arthritis (RA). This study was undertaken to investigate intensification to triple therapy after initial nonbiologic prescription among patients with RA. METHODS: The use of triple therapy among patients with RA in 2009-2014 was evaluated using US insurance claims data. Patients with a health care visit for RA and an initial nonbiologic DMARD prescription were included. Frequencies of intensification to triple therapy or a biologic DMARD and rates of intensification per 6-month time period were calculated. Using Cox regression, we evaluated whether sociodemographic, temporal, geographic, clinical, and health care utilization factors were associated with intensification to triple therapy. Among those patients whose therapy was intensified, we investigated factors associated with triple therapy use by logistic regression. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) for intensification to triple therapy in relation to various clinical and demographic factors were calculated. RESULTS: There were 24,576 patients with a mean +/- SD age of 50.3 +/- 12.3 years, and 78% were female. During the study period, treatment was intensified to biologic DMARDs in 2,739 patients (11.1%) compared to 181 patients (0.7%) whose treatment was intensified to triple therapy. There was no significant change in triple therapy use across calendar years. Patients whose treatment was intensified to triple therapy were more likely to receive glucocorticoids (HR 1.91 [95% CI 1.41 2.60]) compared to patients who did not use glucocorticoids and were more likely to use nonsteroidal antiinflammatory drugs (NSAIDs) (HR 1.48, 95% CI 1.10-1.99 versus no NSAID use). Among those patients whose treatment was intensified to triple therapy or biologic DMARDs, factors significantly associated with triple therapy use included older age, US region (with the highest odds for triple therapy use in the West and lowest odds for triple therapy use in the Northeast), glucocorticoid use, and lower number of outpatient visits within 180 days of initial nonbiologic DMARD prescription. CONCLUSION: Despite reports published during the study period suggesting equivalent efficacy of triple therapy and biologic DMARDs for RA, the use of triple therapy was infrequent and did not increase over time in this large nationwide study. PMID- 26866507 TI - Reply. PMID- 26866508 TI - Flaked sorghum biscuits increase postprandial GLP-1 and GIP levels and extend subjective satiety in healthy subjects. AB - SCOPE: Sorghum grain components may play a role in mechanisms that protect against development of obesity-related chronic diseases. We conducted a randomized, cross-over trial (40 healthy subjects) using whole grain sorghum flaked biscuits to investigate mechanisms related to satiety. METHODS AND RESULTS: Subjects were tested on four occasions after a 12-h fast. At baseline, they consumed 50 grams of one of four treatment meals: white, red, or brown sorghum biscuits or a wheat control. Subjective satiety was measured at 8 time points over four hours. In a subset of 20 subjects, plasma glucose, insulin, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and ghrelin were measured. Subjects reported significantly lower subjective satiety ratings after consuming wheat compared to sorghum biscuits. Incremental area under the plasma concentration-time curve of postprandial GLP-1, GIP and in males, PYY, were significantly higher (p = 0.018, p = 0.031, p = 0.036, respectively) for sorghum breakfasts compared to wheat. Energy intake at a subsequent meal did not differ between treatments. CONCLUSIONS: Sorghum whole grain is a promising novel ingredient in foods targeting satiety as an adjunct for weight control. Evidence is now required from randomized controlled trials that aim to examine specific effects on health outcomes from a sorghum-enriched intervention diet. PMID- 26866509 TI - Molecular Cloning and Expression Determination of p38 MAPK from the Liver and Kidney of Silver Carp. AB - The sequence of p38MAPK in silver carp (Hm-p38a) was cloned and sequenced. Additionally, the acute toxicity of crude microcystins (MCs) on silver carp and induction expression of Hm-p38a by MCs exposure were also determined in this study. The results reveal that the length of Hm-p38a is 2418 bp and it contains a 1086 bp open reading frame. Hm-p38a could encode 361 amino acids. Sequence analysis indicates that Hm-p38a contains the conserved structures of Thr-Gly-Tyr motif and substrate binding site Ala-Thr-Arg-Trp, and it is highly conserved in fish. Phylogenetic analysis reveals that Hm-p38a is more closely related to fish than mammals and it belongs to p38alpha subfamily. Moreover, Hm-p38a in silver carp is constitutively expressed in all examined tissues. In addition, our results indicate that MCs exposure significantly promotes the transcription of Hm p38a in fish liver or kidney, suggesting that mitogen-activated protein kinase should also be the signal pathway of MCs hepatotoxicity in fish. PMID- 26866510 TI - Helicobacter pylori-negative and non-steroidal anti-inflammatory drugs-negative idiopathic peptic ulcers show refractoriness and high recurrence incidence: Multicenter follow-up study of peptic ulcers in Japan. AB - BACKGROUND AND AIM: Helicobacter pylori-negative and non-steroidal anti inflammatory drugs (NSAIDs)-negative idiopathic peptic ulcers (IPU) have attracted attention in Japan and other developed countries. The aim of the present study was to clarify the healing rate of IPU and the risk of recurrence. METHODS: We conducted a retrospective follow-up study of patients with peptic ulcer disease (PUD) who were diagnosed in our previous multicenter-prospective study. Three hundred and eighty-two patients from four institutions in the Tohoku district were enrolled. Enrolled subjects were divided into four groups according to H. pylori infection and intake of NSAIDs. In these patients, we checked treatment course, healing rate during 3 months, and recurrence rate. RESULTS: Healing rates in the: (i) simple H. pylori group; (ii) H. pylori (+)/ NSAIDs (+) group, (iii) simple NSAIDs group; and (iv) IPU group, were 95.0%, 94.9%, 73.3%, and 77.4%, respectively. The healing rate of the IPU group was significantly lower than that of both the simple H. pylori group and the H. pylori (+)/ NSAIDs (+) group (P < 0.01). The recurrence rate of 13.9% in the IPU group was much higher than the 2.1% in the simple H. pylori group (P < 0.01). Additionally, the cumulative recurrence rates by the Kaplan-Meier method in the IPU group were significantly higher than those of the simple H. pylori group (P = 0.015). CONCLUSION: We demonstrated that the clinical course of peptic ulcers is considerably different depending on the cause. IPU could be refractory to treatment and prone to recur compared with simple H. pylori ulcers. PMID- 26866511 TI - Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis. AB - The purpose of this study was to extend established methods for fractional ventilation mapping using (19) F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. (19) F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O2 . Fractional ventilation maps were obtained using a wash-out approach, by switching the breathing mixture to pure O2 , and acquiring images following each successive wash-out breath. The mean fractional ventilation (r) was 0.29 +/- 0.05 for control rats, 0.23 +/- 0.10 for LPS-instilled rats and 0.19 +/- 0.03 for bleomycin-instilled rats. Bleomycin-instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS-instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was -0.005 +/- 0.008 cm(-1) for control rats, 0.013 +/- 0.005 cm(-1) for LPS-instilled rats and 0.009 +/- 0.018 cm(-1) for bleomycin-instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS- and bleomycin-instilled rats showed the opposite trend. Histology confirmed that LPS-instilled rats had a significantly elevated alveolar wall thickness, while bleomycin-instilled rats showed signs of substantial fibrosis. Overall, (19)F MRI may be able to detect the effects of pulmonary inflammation and fibrosis using a simple and inexpensive imaging approach that can potentially be translated to humans. PMID- 26866512 TI - End-of-life care pathways for improving outcomes in caring for the dying. AB - BACKGROUND: This is an updated version of a Cochrane review published in Issue 11, 2013 in the Cochrane Library. In many clinical areas, integrated care pathways are utilised as structured multidisciplinary care plans that detail essential steps in caring for patients with specific clinical problems. In particular, care pathways for the dying have been developed as a model to improve care of patients who are in the last days of life. The care pathways were designed with an aim of ensuring that the most appropriate management occurs at the most appropriate time, and that it is provided by the most appropriate health professional. Since the last update, there have been sustained concerns about the safety of implementing end-of-life care pathways, particularly in the United Kingdom (UK). Therefore, there is a significant need for clinicians and policy makers to be informed about the effects of end-of-life care pathways via a systematic review. OBJECTIVES: To assess the effects of end-of-life care pathways, compared with usual care (no pathway) or with care guided by another end-of-life care pathway across all healthcare settings (e.g. hospitals, residential aged care facilities, community).In particular, we aimed to assess the effects on symptom severity and quality of life of people who are dying, or those related to the care, such as families, carers and health professionals, or a combination of these. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane Library; 2015, Issue 6), MEDLINE, EMBASE, PsycINFO, CINAHL, review articles, trial registries and reference lists of relevant articles. We conducted the original search in September 2009, and the second updated search in July 2015. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-randomised trials or high quality controlled before-and after studies comparing use versus non-use of an end-of-life care pathway in caring for the dying. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the results of the searches against the predetermined criteria for inclusion, assessed risk of bias, and extracted data. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We screened 3028 titles, and included one Italian cluster RCT with 16 general medicine wards (inpatient units in hospitals) and 232 carers of cancer patients in this updated review. We judged the study to be at a high risk of bias overall, mainly due to a lack of blinding and rates of attrition. Only 34% of the participants (range 14% to 75% on individual wards) were cared for in accordance with the care pathway as planned. However, these issues were to be expected due to the nature of the intervention and condition. The study population was all cancer patients in their last days of life. Participants were allocated to care using the Liverpool Care Pathway (LCP-I, Italian version of a continuous quality improvement programme of end-of-life care) or to standard care. The primary outcomes of this review were physical symptom severity, psychological symptom severity, quality of life, and any adverse effects. Physical symptom severity was assessed as overall control of pain, breathlessness, and nausea and vomiting. There was very low quality evidence of a difference in overall control of breathlessness that favoured the Liverpool Care Pathway group compared to usual care: the study reported an odds ratio (OR) of 2.0 with 95% confidence intervals (CIs) 1.1 to 3.8. Very low quality evidence of no difference was found for pain (OR 1.3, 95% CI 0.7 to 2.6, P = 0.461) and nausea and vomiting (OR 1.5, 95% CI 0.7 to 3.2, P = 0.252). None of the other primary outcomes were assessed by the study. Limited data on advance care planning were collected by the study authors, making results for this secondary outcome unreliable. None of our other secondary outcomes were assessed by the study. AUTHORS' CONCLUSIONS: There is limited available evidence concerning the clinical, physical, psychological or emotional effectiveness of end-of-life care pathways. PMID- 26866513 TI - A Molecular Analysis of the Shared Epitope Hypothesis: Binding of Arthritogenic Peptides to DRB1*04 Alleles. AB - OBJECTIVE: The shared epitope hypothesis posits that amino acids QR/KRAA in positions 70-74 of the DRBeta1 chain are responsible for rheumatoid arthritis susceptibility. However, even DRB1*04 alleles containing the shared epitope vary greatly with respect to degrees of susceptibility. This study was undertaken to conduct a molecular examination of the shared epitope hypothesis by measuring binding of arthritogenic peptides to susceptibility and resistance alleles. METHODS: We measured binding of native and citrullinated forms of vimentin(66-78) and alpha-enolase(11-25) and noncitrullinated type II collagen(258-272) to 88 class II alleles on Luminex beads (which includes alleles of many varying degrees of susceptibility and resistance). We expressed DRBeta1*04:01, *04:02, and *08:01 in T2 cells and mutated DRBeta1*04:01 at positions 67, 70, 71, 74, and 86 to corresponding residues in DRB1*04:02, *04:03, *04:04, *04:05, and *08:01. Finally, we measured responses of 4 DRBeta1*04:01 restricted collagen(258-272) T cell hybridomas against wild-type DRBeta1*04:01, *04:02, and all mutated alleles. RESULTS: The most susceptible allele, DRBeta1*04:01, preferentially bound citrullinated vimentin(66-78) and citrullinated alpha-enolase(11-25) over the native forms. DRBeta1*04:02 exhibited no preference for citrullinated peptides, and *08:01 preferred native peptides. Similarly, DRB1*04:01 bound collagen(258 272) , but *04:02 and *08:01 did not. Mutating DRBeta1*04:01 at positions 70, 71, 74, and 86 to the corresponding residues in DRBeta1*04:02 or *08:01 dramatically reduced the specificity for citrullinated peptides and collagen(258-272) binding. CONCLUSION: These observations demonstrate that while amino acids at positions 70, 71, and 74 within the shared epitope in DRBeta1 mediate binding and T cell responses of arthritogenic peptides, position 86 outside the shared epitope also plays a critical role. PMID- 26866514 TI - How Critical is Tele-Medicine to the Rheumatology Workforce? PMID- 26866515 TI - Current management strategies and long-term clinical outcomes of upper extremity venous thrombosis. AB - Essentials Few data exist on outcome of upper extremity deep and superficial vein thrombosis (UEDVT and UESVT). We followed 102 and 55 patients with UEDVT or UESVT, respectively, for a median of 3.5 years. Risk of recurrent venous thromboembolism was low in both diseases, and the mortality high. Postthrombotic symptoms were infrequent and cancer patients had a higher risk of recurrent VTE. SUMMARY: Background There is scant information on the optimal management and clinical outcome of deep and superficial vein thrombosis of the upper extremity (UEDVT and UESVT). Objectives To explore treatment strategies and the incidence of recurrent venous thromboembolism (VTE), mortality, postthrombotic symptoms, and bleeding in patients with UEDVT and UESVT and to assess the prognosis of cancer patients with UEDVT. Patients/methods Follow-up of patients with UEDVT or UESVT, who were enrolled previously in a diagnostic management study. Results We followed 102 and 55 patients with UEDVT and UESVT, respectively, both for a median of 3.5 years. Anticoagulant treatment was started in 100 patients with UEDVT (98%) and in 40 (73%) with UESVT. Nine patients with UEDVT (9%) developed recurrent VTE, 26 (26%) died, 6 (8%) of 72 patients had moderate postthrombotic symptoms, and 5 (5%) experienced major bleeding. One patient with UESVT had a recurrent VTE, 18 (33%) died, none had moderate postthrombotic symptoms, and none had major bleeding. Of the cancer patients with UEDVT, 18% had recurrent VTE vs. 7.5% in non-cancer patients (adjusted hazard ratio 2.2, 95%CI 0.6-8.2). The survival rate was 50% in cancer patients with UEDVT vs. 60% in those without (adjusted HR 0.8, 95%CI 0.4-1.4). Conclusions The risk of recurrent VTE was low in patients with UEDVT, and negligible for UESVT. Mortality was high for both diseases. Postthrombotic symptoms were infrequent and mild. Anticoagulant therapy of UEDVT carried a substantial risk of major bleeding. Cancer patients had a significant risk of recurrent VTE. PMID- 26866516 TI - Brief Report: Predicting Functional Disability: One-Year Results From the Scottish Early Rheumatoid Arthritis Inception Cohort. AB - OBJECTIVE: To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision making. METHODS: The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of >=1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool. RESULTS: Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31). CONCLUSION: In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability. PMID- 26866517 TI - Plant Homeo Domain Finger Protein 8 Regulates Mesodermal and Cardiac Differentiation of Embryonic Stem Cells Through Mediating the Histone Demethylation of pmaip1. AB - Histone demethylases have emerged as key regulators of biological processes. The H3K9me2 demethylase plant homeo domain finger protein 8(PHF8), for example, is involved in neuronal differentiation, but its potential function in the differentiation of embryonic stem cells (ESCs) to cardiomyocytes is poorly understood. Here, we explored the role of PHF8 during mesodermal and cardiac lineage commitment of mouse ESCs (mESCs). Using a phf8 knockout (ph8(-/Y) ) model, we found that deletion of phf8 in ESCs did not affect self-renewal, proliferation or early ectodermal/endodermal differentiation, but it did promote the mesodermal lineage commitment with the enhanced cardiomyocyte differentiation. The effects were accompanied by a reduction in apoptosis through a caspase 3-independent pathway during early ESC differentiation, without significant differences between differentiating wide-type (ph8(+/Y) ) and ph8( /Y) ESCs in cell cycle progression or proliferation. Functionally, PHF8 promoted the loss of a repressive mark H3K9me2 from the transcription start site of a proapoptotic gene pmaip1 and activated its transcription. Furthermore, knockdown of pmaip1 mimicked the phenotype of ph8(-/Y) by showing the decreased apoptosis during early differentiation of ESCs and promoted mesodermal and cardiac commitment, while overexpression of pmaip1 or phf8 rescued the phenotype of ph8( /Y) ESCs by increasing the apoptosis and weakening the mesodermal and cardiac differentiation. These results reveal that the histone demethylase PHF8 regulates mesodermal lineage and cell fate decisions in differentiating mESCs through epigenetic control of the gene critical to programmed cell death pathways. Stem Cells 2016;34:1527-1540. PMID- 26866518 TI - Secukinumab improves patient-reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo-controlled clinical trials. AB - BACKGROUND: Secukinumab is a human interleukin-17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The objective of this analysis was to measure the treatment response on psoriasis-related itching, pain, and scaling via the Psoriasis Symptom Diary (PSD)((c)). METHODS: ERASURE (n = 738) and FIXTURE (n = 1306) were double-blind, multicenter phase 3 studies in adults randomized to secukinumab (300, 150 mg, n = 1144) or placebo (n = 574) (administered at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks) or a biologic active control (FIXTURE only). Patient-reported itching, pain, and scaling were assessed during the first 12 weeks of treatment using the PSD. The results reported here are limited to subjects in the secukinumab and placebo treatment groups who completed the PSD. The proportions of subjects achieving prespecified responses (improvement:reduction of at least 2.2 points for itching, 2.2 points for pain, or 2.3 points for scaling) were compared for secukinumab versus placebo. RESULTS: Overall, 39% of subjects completed the PSD at baseline and Week 12 (n = 453 secukinumab; 225 placebo). Subjects treated with secukinumab achieved significantly greater improvements in itching, pain, and scaling at Week 12 versus placebo (all P < 0.0001) and had significantly greater proportions of itching, pain, and scaling responders at Week 12 versus placebo (all P < 0.05). CONCLUSION: Secukinumab significantly improves patient-reported itching, pain, and scaling in adults with moderate to severe psoriasis compared with placebo. PMID- 26866519 TI - Development of an Asian American parental racial-ethnic socialization scale. AB - OBJECTIVE: To develop a measure of parental racial-ethnic socialization that is appropriate for Asian American families. METHOD: To test the reliability and validity of this new measure, we surveyed 575 Asian American emerging adults (49% female, 79% U.S. born). RESULTS: Using exploratory and confirmatory factor analyses, the results show 7 reliable subscales: maintenance of heritage culture, becoming American, awareness of discrimination, avoidance of other groups, minimization of race, promotion of equality, and cultural pluralism. Tests of factorial invariance show that overall, the subscales demonstrate, at minimum, partial metric invariance across gender, age, nativity, educational attainment, parent educational attainment, geographic region of residence, and Asian-heritage region. Thus, the relations among the subscales with other variables can be compared across these different subgroups. The subscales also correlated with ethnic identity, ethnic centrality, perceptions of discrimination, and pluralistic orientation, demonstrating construct validity. CONCLUSION: In an increasingly complex and diverse social world, our scale will be useful for gaining a better understanding of how Asian American parents socialize their children regarding issues of race, discrimination, culture, and diversity. (PsycINFO Database Record PMID- 26866520 TI - The culture of mentoring: Ethnocultural empathy and ethnic identity in mentoring for minority girls. AB - OBJECTIVES: Many mentoring programs place minority group mentees with majority group mentors. These programs aim to promote beneficial outcomes for their diverse participants. The present study explores mentors of color and White mentors' ethnocultural empathy and ethnic identities in association with their minority group mentees' ethnic identities. METHOD: Our study examined 95 mentoring pairs of middle school girls of color and college student women from both majority and minority group cultural backgrounds. RESULTS: A series of linear regressions revealed an association between mentors' ethnocultural empathy and EI exploration/commitment and minority group mentees' ethnic identity exploration, regardless of the mentors' majority group status. CONCLUSIONS: The results of this preliminary study suggest that mentors' cultural identity and empathy may be linked with mentees' willingness to explore their own ethnic identities. We discuss the implications for mentoring programs that seek to build participants' ethnic identities and ethnocultural empathy. (PsycINFO Database Record PMID- 26866521 TI - Glucose control in acute brain injury: does it matter? AB - PURPOSE OF REVIEW: Alterations of blood glucose levels are secondary insults with detrimental consequences for the injured brain. Here, we review various aspects of brain glucose metabolism and analyze the evidence on glycemic control during acute brain injury. RECENT FINDINGS: An essential component in the overall management of acute brain injury, especially during the acute phase, is maintaining adequate and appropriate control of serum glucose. This is one of the few physiological parameters that is modifiable. Hypoglycemia should be rigorously avoided. However, intensive insulin therapy is associated with unacceptable rates of hypoglycemia and metabolic crisis, and does not necessarily provide benefit. Hyperglycemia is harmful to the injured brain as it compromises microcirculatory blood flow, increases blood-brain barrier permeability, and promotes inflammation. In addition, it triggers osmotic diuresis, hypovolemia, and immunosuppression. SUMMARY: Glucose is the primary energy substrate for the brain. During injury, the brain increases its needs and is vulnerable to glucose deficit. In these situations, alternative fuel can be lactate, which has potential implications for future research. In this review, various pathophysiological aspects of glucose metabolism during acute brain injury, as well as the risks, causes, and consequences of glucose deficiency or excess, will be discussed. PMID- 26866522 TI - Postpartum Weight Retention and Subsequent Pregnancy Outcomes. AB - The effects of postpartum weight retention on gestational weight gain in successive pregnancies require elucidation. The purpose of the study was (1) to examine the association between postpartum weight retention and subsequent adherence to the Institute of Medicine gestational weight gain guidelines and (2) to determine whether the association varies by body mass index status and affects birth outcomes. Florida vital records for 2005-2010 were analyzed using chi tests and multivariable Poisson regression, adjusted for interpregnancy interval, tobacco use, maternal age, and race/ethnicity. Obese women who gained inadequate weight were more likely to retain weight between pregnancies than obese women who met or exceeded the recommended weight gain. Risks for preterm birth increased among women with inadequate weight and decreased among women with excessive weight gain. Gaining excessive weight was protective for small-for-gestational age infants in all body mass index categories but increased the risks for large for-gestational age infants. Underweight and normal weight women who gained in excess were 40% more likely to develop hypertension than normal weight women who gained within the recommended amount. Obese women who retain or gain weight postpartum are at increased risk for inadequate weight gain in a successive pregnancy. Achieving Institute of Medicine-recommended gestational weight gain is essential for preventing adverse maternal and infant outcomes. PMID- 26866523 TI - Hepatitis B and C prevalence in Portugal: disparity between the general population and high-risk groups. AB - BACKGROUND AND AIMS: The prevalence of anti-HCV and HBsAg in Portugal has been shown to be elevated in high-risk groups, such as intravenous drug-users and incarcerated individuals. However, in the general population, prevalence remains largely unknown. The aims of this study were to estimate the prevalence of anti HCV and HBsAg in the general Portuguese population and identify associated risk factors. MATERIALS AND METHODS: We carried out a nationwide, population-based cross-sectional study of adults resident in mainland Portugal. Serology for HBsAg, anti-HBc, anti-HBs, and anti-HCV was performed. Anti-HCV-positive individuals were tested for HCV RNA by PCR. RESULTS: Of 1685 participants, 50.6% were men, mean age 50.2+/-18.3 years. In terms of hepatitis C, the prevalence of anti-HCV was 0.54% [95% confidence interval (CI): 0.2-0.9] and 0.12% (95% CI: 0.0 0.3) were viremic, with peak prevalence among individuals 35-64 years of age (0.8%), men (0.8%), and individuals from Lisbon and Tagus Valley region (1.9%).In terms of hepatitis B, the estimated prevalence of HBsAg was 1.45% (95% CI: 0.9 2.0). A higher prevalence was found in individuals who were 35-64 years old (2.2%), in men (2.5%), and in the Northern region (2.6%).The presence of positive serological markers of hepatitis C virus and hepatitis B virus infection did not correlate with elevated aminotransferases, race, place of birth, and alcohol consumption. CONCLUSION: These results suggest a low endemicity for both hepatitis B and hepatitis C in the general population, in contrast to a very high prevalence in risk groups, thus suggesting that targeted screening to high-risk groups may be more cost-effective than general population screening. PMID- 26866524 TI - Management of gastric varices: a French national survey. AB - BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices. METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire. RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: beta-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; P<0.001) and TIPS (78.5 vs. 3.5%; P<0.001). Early TIPS was proposed by 53.6% (72.1 vs. 39.2%; P<0.001). Glue obliteration was performed under general anesthesia (86.1%) using Glubran (43.1%) or Histoacryl (52.9%), and lipiodol (78.8%) with varying degrees of dilution (1 : 10 to 3 : 4). The injected volume per varix varied widely (1-20 ml). Glue obliteration, band ligation, or both were used by, respectively, 64.2, 18.2, and 17.5% of practitioners. Almost all hepatogastroenterologists (98%) performed secondary prophylaxis: beta-blockers 74.7% (75.0 vs. 74.4%, university vs. general hospitals; P=0.93), glue obliteration 66.0% (76.9 vs. 57.6%; P=0.013), and TIPS 30.0% (39.1 vs. 23.3%; P=0.037). CONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies. PMID- 26866525 TI - PHOTORECEPTOR OUTER SEGMENT LENGTH AND OUTER FOVEAL THICKNESS AS FACTORS ASSOCIATED WITH VISUAL OUTCOME AFTER VITRECTOMY FOR VITREOMACULAR TRACTION SYNDROME. AB - PURPOSE: To investigate the predictive factors for postoperative best-corrected visual acuity (BCVA) in patients with vitreomacular traction syndrome treated with vitrectomy. METHODS: The records of 21 patients with 21 eyes that underwent vitrectomy for vitreomacular traction syndrome and followed for at least 12 months were retrospectively reviewed. The BCVA and spectral domain optical coherence tomography findings were investigated preoperatively and at 1, 3, 6, and 12 months postoperatively. Axial length was measured preoperatively. The correlations between 12-month postoperative BCVA and preoperative parameters, including BCVA, age, axial length, central foveal thickness, outer foveal thickness, and photoreceptor outer segment length, were evaluated. RESULTS: Twelve-month postoperative BCVA was significantly negatively correlated with preoperative outer foveal thickness and photoreceptor outer segment length (outer foveal thickness: P = 0.029, r = -0.501; photoreceptor outer segment length: P = 0.022, r = -0.523, respectively) but not correlated with age, axial length, preoperative BCVA, and preoperative central foveal thickness (age: P = 0.346, r = 0.216; axial length: P = 0.333, r = 0.242; BCVA: P = 0.202, r = 0.290; central foveal thickness: P = 0.065, r = -0.410, respectively). CONCLUSION: Preoperative outer foveal thickness and photoreceptor outer segment length could be good predictive factors of postoperative BCVA in patients with vitreomacular traction syndrome. PMID- 26866526 TI - INDUCTION OF MACULAR DETACHMENT FOR THE TREATMENT OF PERSISTENT OR RECURRENT IDIOPATHIC MACULAR HOLES. AB - PURPOSE: To analyze the efficacy of induced macular detachment for the treatment of persistent or recurrent idiopathic macular holes after treatment with one or more standard pars plana vitrectomies (PPVs) with internal limiting membrane peeling. METHODS: This study is a retrospective consecutive case series of 10 patients who underwent a PPV with subretinal balanced salt solution injection from 2011 to 2014 to treat persistent or recurrent idiopathic macular holes. All patients had previously undergone PPV with internal limiting membrane peeling. Visual acuity, ocular examination findings, and optical coherence tomographic images were reviewed preoperatively and postoperatively to assess the anatomical and visual outcomes of this procedure. RESULTS: Nine of the 10 patients who underwent the procedure had closure of their macular holes postoperatively (90%) and remained closed 6 months postoperatively. Most patients reported a subjective visual improvement. A mean objective visual improvement of 16 letters (Early Treatment Diabetic Retinopathy Study, 0.324 logMAR) was seen between preoperative and 6-month postoperative assessments of all patients (pre = 1.490, post = 1.166; P = 0.022). Subgroup analysis of patients with successful closure revealed 20 letters of improvement (0.398 logMAR) in visual acuity (pre = 1.491, post = 1.093; P = 0.004). There were no intraoperative or postoperative complications. CONCLUSION: In eyes with persistent or recurrent idiopathic macular holes after standard PPV with internal limiting membrane peeling, repeat PPV with subretinal balanced salt solution injection to create a macular detachment may be a viable surgical treatment option. Our results show improved anatomical and visual outcomes postoperatively that compare favorably to other case series describing various surgical treatments for these challenging cases. PMID- 26866527 TI - SHORT-TERM EFFECT OF INTRAVITREAL RANIBIZUMAB THERAPY ON MACULAR EDEMA AFTER BRANCH RETINAL VEIN OCCLUSION. AB - PURPOSE: To assess the short-term effect of intravitreal ranibizumab (IVR) on macular edema after branch retinal vein occlusion. METHODS: Twenty-three eyes with macular edema after branch retinal vein occlusion were enrolled in a prospective observational study. After administering one IVR injection (0.5 mg) for the first time, the authors measured the foveal thickness (FT) before and 2 hours, 1 and 3 days, 1 week, and 1 month later and the best-corrected visual acuity at all times except 2 hours, and determined the changes from baseline (DeltaFT and DeltaVA). RESULTS: The mean FT decreased significantly (P < 0.0001) from 522 +/- 131 MUm to 458 +/- 96 MUm after 2 hours. The mean logarithm of the minimum angle of resolution (logMAR) visual acuity improved significantly (P < 0.05) after 1 day from 0.69 +/- 0.40 to 0.55 +/- 0.34 (20/98-20/70, Snellen equivalent). The DeltaFT after 2 hours was significantly positively correlated with the DeltaFT after 1 week (r = 0.76, P < 0.001) and 1 month (r = 0.67, P < 0.001). The DeltaVA after 1 day was correlated positively with the DeltaVA after 1 week (r = 0.80, P < 0.001) and 1 month (r = 0.59, P < 0.01). CONCLUSION: Structural and functional effects of IVR for branch retinal vein occlusion occurred within 1 day. The short-term effects of IVR may predict the outcome of the therapy at 1 week and 1 month after IVR in macular edema secondary to branch retinal vein occlusion. PMID- 26866528 TI - NEAR VISION OUTCOME IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION TREATED WITH AFLIBERCEPT. AB - PURPOSE: The aim of this study was to investigate the outcome in near vision and the best-corrected visual acuity in patients with wet, age-related macular degeneration treated with aflibercept in a fixed bimonthly regimen in an ordinary clinical setting. METHODS: The study was a retrospective, nonrandomized consecutive case series including 85 patients with wet, age-related macular degeneration followed for 18 months. During the first year all the patients received aflibercept injections in a fixed regimen at the following time points: Month 0, 1, 2, 4, 6, 8, 10, and 12. From Month 12 to Month 18, patients were treated with a treat and extend algorithm. RESULTS: The median near visual acuity improved from 12 points (95% confidence interval [CI] 10.5-13.4) at baseline to 5 points both at Month 12 (95% CI 3.8-6.2) and at Month 18 (95% CI 3.6-6.4) (P < 0.0001). At the 18-month visit, 58% (42/73) of the patients had a near visual acuity of at least 5 points compared with 7% (6/85) (P < 0.0001) at baseline. Best-corrected visual acuity improved from 60.9 letters (Snellen 20/63) (95% CI 58.4-63.4) at baseline to 68.1 letters (20/40) (95% CI 65.3-70.9) (P < 0.001) at Month 12 and 69.6 letters (20/40) (95% CI 66.7-72.5) (P < 0.001) at Month 18. CONCLUSION: Significant improvements were found in near vision and best-corrected visual acuity. The improvement in near vision was comparably greater than the change in best-corrected visual acuity. Monitoring near vision can contribute additional information when managing the patient with wet, age-related macular degeneration. PMID- 26866529 TI - POSSIBLE MOLECULAR BASIS OF BEVACIZUMAB THERAPY FOR MACULAR EDEMA IN BRANCH RETINAL VEIN OCCLUSION. AB - PURPOSE: To investigate changes in the aqueous humor levels of 11 factors/cytokines (including vascular endothelial growth factor [VEGF] receptors, growth factors, and inflammatory factors) after intravitreal injection of bevacizumab (IVB), as well as the relationship between changes of these factors and improvement of macular edema in patients with branch retinal vein occlusion and macular edema. METHODS: In 29 patients with branch retinal vein occlusion who received IVB twice for macular edema at monthly intervals, aqueous humor samples were obtained during IVB. Levels of VEGF, soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor, soluble intercellular adhesion molecule-1, monocyte chemotactic protein 1, platelet-derived growth factor-AA, and interleukin (IL)-6, IL-8, IL-12 (p70), and IL-13 were measured by the suspension array method. Foveal thickness was examined by optical coherence tomography before and 1 month after IVB, and the improvement of macular edema was evaluated by calculating the percent change of foveal thickness. RESULTS: Aqueous humor levels of sVEGFR-1, VEGF, monocyte chemotactic protein 1, and IL-6 showed a significant decrease at 1 month after IVB compared with baseline (P = 0.013, P < 0.001, P = 0.047, and P = 0.019, respectively). There was a significant negative correlation between the change of sVEGFR-1 or platelet-derived growth factor-AA after IVB and the improvement of macular edema (P = 0.004 and P = 0.036, respectively). CONCLUSION: These findings suggest that improvement of macular edema by IVB is related to inhibition of sVEGFR-1 and platelet-derived growth factor-AA, but not VEGF, in patients with branch retinal vein occlusion. Soluble VEGF receptor-1 and platelet-derived growth factor-AA might be useful indicators of the response of macular edema. PMID- 26866530 TI - Albumin Supplementation as a Therapeutic Strategy in Cardiac Surgery: Useful Tool or Expensive Hobby? PMID- 26866531 TI - Person-centred care: an overview of reviews. AB - BACKGROUND: Existing evidence suggests that a person-centred approach can improve coordination and access to health care and services. OBJECTIVES: This overview sought to: (1) identify and define components of person-centred care; (2) explore nursing and health-care provider behaviours that are person-centred; and (3) identify systems level supports required to enable person-centred care. METHODS: An overview of reviews was conducted to locate synthesized literature published between June 2005 and April 2014. Two independent reviewers screened, extracted data and quality appraised the sources. Results were synthesized narratively. RESULTS: A total of 46 articles were deemed relevant to this overview. This paper synthesizes the results of 43 of the 46 articles. A universal definition of person-centred care was not found, however; common components, associated health care provider behaviours and the organizational supports required for person centred care are discussed. CONCLUSIONS: Key findings from this review outline that health-care providers and organizations need to promote person-centred care by engaging persons in partnerships, shared decision-making, and meaningful participation in health system improvement. PMID- 26866532 TI - The Effect of Cigarette Smoking on Lung Function in Young Adults with Asthma. AB - RATIONALE: Life-course persistent asthma and tobacco smoking are risk factors for irreversible airflow obstruction. It is often assumed that smoking and asthma have additive or multiplicative effects on the risk for airflow obstruction, but this has not been demonstrated in prospective studies of children with persistent asthma. OBJECTIVES: To investigate the effects of smoking and asthma on the development of airflow obstruction in a population-based birth cohort followed to age 38 years. METHODS: Reports of childhood asthma from ages 9, 11, and 13 and self-reports of adult asthma at ages 32 and 38 years were used to define childhood-onset persistent asthma (n = 91), late-onset asthma (n = 93), asthma in remission (n = 85), and nonasthmatic (n = 572) phenotypes. Cumulative tobacco smoking histories and spirometry were obtained at ages 18, 21, 26, 32, and 38 years. Analyses were by generalized estimating equations adjusting for childhood spirometry, body mass index, age, and sex. MEASUREMENTS AND MAIN RESULTS: Smoking history and childhood-onset persistent asthma were both associated with lower FEV1/FVC ratios. Associations between smoking and FEV1/FVC ratios were different between asthma phenotypes (interaction P < 0.001). Smoking was associated with lower prebronchodilator and post-bronchodilator FEV1/FVC ratios among subjects without asthma and those with late-onset or remittent asthma, but smoking was not associated with lower FEV1/FVC ratios among those with childhood-onset persistent asthma. CONCLUSIONS: Childhood-onset persistent asthma is associated with airflow obstruction by mid-adult life, but this does not seem to be made worse by tobacco smoking. We found no evidence that smoking and childhood-persistent asthma have additive or multiplicative effects on airflow obstruction. PMID- 26866533 TI - Social stress facilitates risk in youths. AB - This research examined the influence of social stress on risk processes in youths. Study 1 (N = 89) randomly assigned male youths to perform either a stressful social-evaluative or nonstressful control task followed by a risk perception measure. Compared to controls, social stress participants perceived less risk in their environment. Study 2 (N = 188) extended findings by testing effects of social stress on risk perception in males and females, and across 3 age groups: teenagers (15-19), young adults (25-40), and older adults (60-75). Replicating Study 1, teenagers experiencing social stress perceived less risk than age-matched controls. However, adults assigned to experience social stress reported greater risk perception compared to their age-matched controls. Effects of social stress also extended to risk-taking behavior. Stressed teenagers engaged in more risk-taking behavior relative to controls, and showed increased reward and lowered cost sensitivity during decision-making. These findings offer basic and translational value regarding factors that influence how youths evaluate risk. PMID- 26866536 TI - Role of Resonances in the Transmission of Surface Plasmon Polaritons between Nanostructures. AB - Understanding how surface plasmon polaritons (SPPs) propagate in metal nanostructures is important for the development of plasmonic devices. In this paper, we study the transmission of SPPs between single-crystal gold nanobars on a glass substrate using transient absorption microscopy. The coupled structures were produced by creating gaps in single nanobars by focused ion beam milling. SPPs were launched by focusing the pump laser at the end of the nanobar, and the transmission across the gaps was imaged by scanning the probe laser over the nanostructure. The results show larger losses at small gap sizes. Finite element method calculations were used to investigate this effect. The calculations show two main modes for nanobars on a glass surface: a leaky mode localized at the air gold interface, and a bound mode localized at the glass-gold interface. At specific gap sizes (approximately 50 nm for our system), these SPP modes can excite localized surface plasmon modes associated with the gap, which dissipate energy. This increases the energy losses at small gap sizes. Experiments and simulations were also performed for the nanobars in microscope immersion oil, which creates a more homogeneous optical environment, and consistent results were observed. PMID- 26866537 TI - Therapeutic advances and risk factor management: our best chance to tackle dementia? PMID- 26866538 TI - Ebola and the WHO: a journey from toothless tiger to global dragon? PMID- 26866539 TI - Multidisciplinary approach to reducing pharmaceutical misuse. PMID- 26866541 TI - Non-reimbursement for preventable health care-acquired conditions. PMID- 26866542 TI - The value of consultant-led ward rounds for patient safety. PMID- 26866543 TI - Lessons from Wales--how to embed sustainability and prevention in health care. PMID- 26866544 TI - Uptake of novel oral anticoagulants in Australia. PMID- 26866545 TI - Pitfalls in photographing radiological images from computer screens. PMID- 26866546 TI - A rare cause of intrathoracic mass. PMID- 26866547 TI - Novel insights, challenges and practical implications of DOHaD-omics research. AB - Research investigating the developmental origins of health and disease (DOHaD) has never had the technology to investigate physiology in such a data-rich capacity and at such a microlevel as it does now. A symposium at the inaugural meeting of the DOHaD Society of Australia and New Zealand outlined the advantages and challenges of using "-omics" technologies in DOHaD research. DOHaD studies with -omics approaches to generate large, rich datasets were discussed. We discuss implications for policy and practice and make recommendations to facilitate successful translation of results of future DOHaD-omics studies. PMID- 26866548 TI - Factors contributing to frequent attendance to the emergency department of a remote Northern Territory hospital. AB - OBJECTIVES: To determine the clinical and environmental variables associated with frequent presentations by adult patients to a remote Australian hospital emergency department (ED) for reasons other than chronic health conditions. DESIGN: Unmatched case-control study of all adult patients attending Katherine Hospital ED between 1 January and 31 December 2012. PARTICIPANTS: Cases were defined as frequent attenders (FAs) without a chronic health condition who presented to the ED six or more times during the 12-month period. A single presentation was randomly selected for data collection. Controls were patients who presented on only one occasion. OUTCOME MEASURES: Basic demographic data were collected, including clinical outcomes, Indigenous status, living arrangements, and whether alcohol and violence contributed to the presentation. Environmental variables were extracted from the Bureau of Meteorology database and mapped to each presentation. RESULTS: FAs were much more likely to be homeless (odds ratio [OR], 16.4; P < 0.001) and to be Aboriginal (OR, 2.16; P < 0.001); alcohol as a contributing factor was also more likely (OR, 2.77; P = 0.001). FAs were more likely to present in hotter, wetter weather, although the association was statistically weak. Clinical presentations by cases and controls were similar; the annual death rates for both groups were high (3.6% and 1.5%, respectively). CONCLUSIONS: There was a strong association between FA and Aboriginal status, homelessness and the involvement of alcohol, but alcohol was more likely to contribute to presentation by non-Aboriginal FAs who had stable living conditions. FAs and non-FAs had similar needs for emergency medical care, with strikingly higher death rates than the national average in both groups. As a result of this study, Katherine Hospital has initiated a Frequent Attender Pathway that automatically triggers a dedicated ED service for those at greatest clinical risk. Homelessness is a serious problem in the Northern Territory, and is associated with poor health outcomes. PMID- 26866549 TI - Socio-demographic and structural barriers to being tested for chlamydia in general practice. AB - OBJECTIVES: To investigate socio-demographic and structural factors associated with not providing a specimen for chlamydia testing following a request by a general practitioner. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of chlamydia testing data for men and women aged 16-29 years attending general practice clinics participating in a cluster randomised controlled trial evaluating the effectiveness of a chlamydia testing intervention. The study period was the 2013 calendar year. OUTCOME: The proportion of chlamydia test requests for which the patient did not provide a specimen for testing. RESULTS: During the study period, there were 13 225 chlamydia test requests, for which a chlamydia test was not performed in 2545 instances (19.2%; 95% CI, 16.5-22.3%). Multivariate analysis indicated that the odds for not undertaking a requested test were higher for men (adjusted odds ratio [aOR], 1.4; 95% CI, 1.3-1.6), those aged 16-19 years (aOR, 1.3; 95% CI, 1.1-1.4), those living in areas of greater socio-economic disadvantage (aOR, 1.2; 95% CI, 1.1-1.4 for each additional quintile of Index of Relative Socio-economic Disadvantage), and those attending clinics without on-site pathology collection (aOR, 1.4; 95% CI, 1.0-1.9). CONCLUSION: One in five young people did not submit a specimen for chlamydia testing despite their GP requesting it. This highlights the need for clinics to establish systems which ensure that men and those aged 16-19 years undertake chlamydia tests requested by a GP. PMID- 26866550 TI - Acute heart failure admissions in New South Wales and the Australian Capital Territory: the NSW HF Snapshot Study. AB - OBJECTIVE: The primary aim of the NSW Heart Failure (HF) Snapshot was to obtain a representative cross-sectional view of patients with acute HF and their management in New South Wales and Australian Capital Territory hospitals. DESIGN AND SETTING: A prospective audit of consecutive patients admitted to 24 participating hospitals in NSW and the ACT with a diagnosis of acute HF was conducted from 8 July 2013 to 8 August 2013. RESULTS: A total of 811 participants were recruited (mean age, 77 +/- 13 years; 58% were men; 42% had a left ventricular ejection fraction >= 50%). The median Charlson Comorbidity Index score was 3, with ischaemic heart disease (56%), renal disease (55%), diabetes (38%) and chronic lung disease (32%) the most frequent comorbidities; 71% of patients were assessed as frail. Intercurrent infection (22%), non-adherence to prescribed medication (5%) or to dietary or fluid restrictions (16%), and atrial fibrillation/flutter (15%) were the most commonly identified precipitants of HF. Initial treatment included intravenous diuretics (81%), oxygen therapy (87%), and bimodal positive airways pressure or continuous positive airways pressure ventilation (17%). During the index admission, 6% of patients died. The median length of stay in hospital was 6 days, but ranged between 3 and 12 days at different hospitals. Just over half the patients (59%) were referred to a multidisciplinary HF service. Discharge medications included angiotensin converting enzyme inhibitors/angiotensin receptor blockers (59%), beta-blockers (66%) and loop diuretics (88%). CONCLUSIONS: Patients admitted to hospital with acute HF in NSW and the ACT were generally elderly and frail, with multiple comorbidities. Evidence-based therapies were underused, and there was substantial interhospital variation in the length of stay. We anticipate that the results of the HF Snapshot will inform the development of strategies for improving the uptake of evidence-based therapies, and hence outcomes, for HF patients. PMID- 26866551 TI - Emergency department presentations with mammalian bite injuries: risk factors for admission and surgery. AB - OBJECTIVES: The incidence of animal bite injuries in Australia is high. There is currently no established method for reliably predicting whether a patient with a bite injury will require admission to hospital or surgery. DESIGN: A retrospective audit of mammalian bite injuries at seven major hospitals in Melbourne, Victoria, over a 2-year period. The associations between each predictor and outcome of interest were analysed with univariate and multiple regression analyses. SETTING: Seven major hospitals in Melbourne, Victoria: the Alfred Hospital, Austin Hospital, Frankston Hospital, Monash Medical Centre, Royal Melbourne Hospital, St Vincent's Hospital and Western Hospital. PARTICIPANTS: Patients presenting to emergency departments with mammalian bite injuries. MAIN OUTCOME MEASURES: Hospital admission, intravenous antibiotic therapy, surgery, reoperation, readmission. RESULTS: We identified 717 mammalian bite injuries. The mean age of the patients was 36.5 years (median, 34 years; range, 0-88 years), with an equal number of males and females. The overall rate of hospital admission was 50.8%, and the mean length of stay was 2.7 days. Intravenous antibiotics were administered in 46% of cases; surgery was undertaken in 43.1% of cases. The re-operation rate was 4.5%, the re-admission rate was 3%. CONCLUSIONS: Our study provides a detailed epidemiological analysis of animal bite injuries at seven major hospitals in Victoria. Risk factors for hospitalisation and surgery may assist in identifying patients who require admission and surgical intervention. PMID- 26866553 TI - The early bird and the worm: a case of cercarial dermatitis. PMID- 26866552 TI - Statins and tendinopathy: a systematic review. AB - OBJECTIVES: To systematically review the evidence on whether statin therapy, commonly used in clinical practice to treat hypercholesterolaemia for primary and secondary prevention of cardiovascular disease, contributes to tendinopathy; and to examine causality according to the Bradford Hill criteria. STUDY DESIGN: A systematic review of studies examining the relationship between statin therapy and tendinopathy. Included studies were rated based on their methodological quality. A best evidence synthesis was used to summarise the results, and Bradford Hill criteria were used to assess causation. DATA SOURCES: Ovid MEDLINE, CINAHL Plus, PubMed and Embase databases. STUDY SELECTION: We included adult human studies published in the English language between January 1966 and October 2015. Study designs eligible for inclusion were randomised controlled trials and cross-sectional, cohort or case-control studies. DATA SYNTHESIS: Four studies (three cohort studies and one case-control study) were included, with a mean methodological quality score of 67%. Three studies were deemed high quality. Tendon rupture was the primary outcome in three studies, and rotator cuff disease in the other. All studies found no positive association between statin therapy and tendon rupture for the total study population. There was evidence that simvastatin reduces the risk of tendinopathy. CONCLUSION: To date, there is a paucity of evidence to implicate statin therapy as a well established risk factor or causal mechanism for tendon rupture in the general population. There is strong evidence that simvastatin reduces the risk of tendinopathy. PMID- 26866554 TI - Shiitake dermatitis: the tale of an under-recognised, undercooked fungus. PMID- 26866555 TI - Massive subdural haematoma and dementia: a "yin and yang" paradigm. PMID- 26866556 TI - John Stuart Newlinds, OAM, MB BS, FRCOG, FRANZCOG, DGO. PMID- 26866559 TI - Vladimir Albert Lovric, MB BS, FRCPA, DipClinPath, GradDipPH, FRCPath, FRACP. PMID- 26866560 TI - Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation. AB - Levamisole has been identified as a cocaine adulterant in the United States since 2002. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, measurement of levamisole in human samples of cocaine users has become increasingly important. To our best knowledge, only five deaths are reported (one twice) as a result of complications secondary to levamisole-tainted cocaine and none of these cases reports the post-mortem levamisole concentration. In this article, we present the post-mortem levamisole concentrations in fluids and tissues in two young cocaine users, dead after levamisole-adulterated cocaine intake. With the dearth of levamisole reported concentrations in literature, this particular report is of interest to the forensic toxicological and pathological communities. This article aims to be a supplementary alert to aware the risk that may occur using levamisole-adulterated cocaine and an incentive to publication of toxicity reports and new researches involving the combination of levamisole and cocaine. PMID- 26866562 TI - A novel biosensor based on competitive SERS immunoassay and magnetic separation for accurate and sensitive detection of chloramphenicol. AB - The accurate and sensitive detection of chloramphenicol (CAP) is particularly imperative to public health and safety. Here, we present a novel sensor for residual CAP detection based on competitive surface-enhanced Raman scattering (SERS) immunoassay and magnetic separation. In this nanosensor, functionalized Au nanoparticles (AuNPs) were labeled with the Raman reporter molecule (e.g. 4,4' dipyridyl). With the addition of free CAP, a competitive immune reaction was initiated between free CAP and above AuNPs for conjugating with CAP antibody modified magnetic nanoparticles (MNPs). Instead of the solid substrate, the antibody conjugated-magnetic beads were used as supporting materials and separation tools in the present sensor. With the aid of a magnet, the mixture was removed from the supernatant for concentration effects. This caused obvious change of SERS signal intensity obtained from supernatant. The SERS signals were collected from the supernatant directly, which made the SERS measurements more stable, repeatable and reliable. The proposed SERS-based magnetic immunosensor allows us to detect CAP in a fast, selective and sensitive (1.0 pg/mL) manner over a wide concentration range ( 1-1 * 10(4)pg/mL). In addition, these results demonstrate that this immunosensor holds great potential for the detection of antibiotics in real aquatic environment, which is crucial to our life. PMID- 26866561 TI - A novel polydopamine-based chemiluminescence resonance energy transfer method for microRNA detection coupling duplex-specific nuclease-aided target recycling strategy. AB - MicroRNAs (miRNAs), functioning as oncogenes or tumor suppressors, play significant regulatory roles in regulating gene expression and become as biomarkers for disease diagnostics and therapeutics. In this work, we have coupled a polydopamine (PDA) nanosphere-assisted chemiluminescence resonance energy transfer (CRET) platform and a duplex-specific nuclease (DSN)-assisted signal amplification strategy to develop a novel method for specific miRNA detection. With the assistance of hemin, luminol, and H2O2, the horseradish peroxidase (HRP)-mimicking G-rich sequence in the sensing probe produces chemiluminescence, which is quickly quenched by the CRET effect between PDA as energy acceptor and excited luminol as energy donor. The target miRNA triggers DSN to partially degrade the sensing probe in the DNA-miRNA heteroduplex to repeatedly release G-quadruplex formed by G-rich sequence from PDA for the production of chemiluminescence. The method allows quantitative detection of target miRNA in the range of 80 pM-50 nM with a detection limit of 49.6 pM. The method also shows excellent specificity to discriminate single-base differences, and can accurately quantify miRNA in biological samples, with good agreement with the result from a commercial miRNA detection kit. The procedure requires no organic dyes or labels, and is a simple and cost-effective method for miRNA detection for early clinical diagnosis. PMID- 26866563 TI - Triple cascade reactions: An ultrasensitive and specific single tube strategy enabling isothermal analysis of microRNA at sub-attomole level. AB - Sensitive and specific analysis of microRNAs (miRNAs) in a single tube without the need of thermal cycler instrument would greatly facilitate the investigation of miRNA-associated regulatory circuits and diseases. Homogeneous isothermal amplification assays are attractive in conducting single tube assays that can minimize contamination-prone steps and simplifies assay procedures. However, the relative low amplification efficiency and high detection background remain as bottlenecks restricting their more versatile applications. In this work, we have developed a novel isothermal exponential enzymatic amplification (IEEA) strategy for miRNAs analysis. By rational triple cascade amplification cycles of target recycling, nicking-replication reaction, and DNAzyme catalysis, the strategy exhibited high signal amplification efficiency (10(4)-10(9) folds of amplification in 1h) with very low detection background and excellent specificity. As a result, the miR-27a target model was rapidly determined with a limit of detection down to 0.79 aM (S/N=3), corresponding to 94 copies of the miRNA molecule in a 200 MUL sample solution. The levels of miR-27a in atherosclerotic sprague-dawley rats were accurately quantified. The strategy is anticipated to have an important impact on the development of simple and rapid molecular diagnostic applications for any short oligonucleotides. PMID- 26866564 TI - ELISA-PLA: A novel hybrid platform for the rapid, highly sensitive and specific quantification of proteins and post-translational modifications. AB - Detection of low-abundance proteins and their post-translational modifications (PTMs) remains a great challenge. A conventional enzyme-linked immunosorbent assay (ELISA) is not sensitive enough to detect low-abundance PTMs and suffers from nonspecific detection. Herein, a rapid, highly sensitive and specific platform integrating ELISA with a proximity ligation assay (PLA), termed ELISA PLA, was developed. Using ELISA-PLA, the specificity was improved by the simultaneous and proximate recognition of targets through multiple probes, and the sensitivity was significantly improved by rolling circle amplification (RCA). For GFP, the limit of detection (LOD) was decreased by two orders of magnitude compared to that of ELISA. Using site-specific phospho-antibody and pan-specific phospho-antibody, ELISA-PLA was successfully applied to quantify the phosphorylation dynamics of ERK1/2 and the overall tyrosine phosphorylation level of ERK1/2, respectively. ELISA-PLA was also used to quantify the O-GlcNAcylation of AKT, c-Fos, CREB and STAT3, which is faster and more sensitive than the conventional immunoprecipitation and western blotting (IP-WB) method. As a result, the sample consumption of ELISA-PLA was reduced 40-fold compared to IP WB. Therefore, ELISA-PLA could be a promising platform for the rapid, sensitive and specific detection of proteins and PTMs. PMID- 26866565 TI - Intrinsic Two-Dimensional Organic Topological Insulators in Metal Dicyanoanthracene Lattices. AB - We predict theoretical existence of intrinsic two-dimensional organic topological insulator (OTI) states in Cu-dicyanoanthracene (DCA) lattice, a system that has also been grown experimentally on Cu substrate, based on first-principle density functional theory calculations. The pz-orbital Kagome bands having a Dirac point lying exactly at the Fermi level are found in the freestanding Cu-DCA lattice. The tight-binding model analysis, the calculated Chern numbers, and the semi infinite Dirac edge states within the spin-orbit coupling gaps all confirm its intrinsic topological properties. The intrinsic TI states are found to originate from a proper number of electrons filling of the hybridized bands from Cu atomic and DCA molecular orbitals based on which similar lattices containing noble metal atoms (Au and Cu) and those molecules with two CN groups (DCA and cyanogens) are all predicted to be intrinsic OTIs. PMID- 26866566 TI - Red wine activates plasma membrane redox system in human erythrocytes. AB - In the present study, we report that polyphenols present in red wine obtained by a controlled microvinification process are able to protect human erythrocytes from oxidative stress and to activate Plasma Membrane Redox System (PMRS). Human plasma obtained from healthy subjects was incubated in the presence of whole red wine at a concentration corresponding to 9.13-73 MUg/ml gallic acid equivalents to verify the capacity to protect against hypochlorous acid (HOCl)-induced plasma oxidation and to minimize chloramine formation. Red wine reduced hemolysis and chloramine formation induced by HOCl of 40 and 35%, respectively. PMRS present on human erythrocytes transfers electrons from intracellular molecules to extracellular electron acceptors. We demonstrated that whole red wine activated PMRS activity in human erythrocytes isolated from donors in a dose-dependent manner with a maximum at about 70-100 MUg/ml gallic acid equivalents. We also showed that red wine increased glutathione (GSH) levels and erythrocytic antioxidant capacity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) quenching assay. Furthermore, we reported that GSH played a crucial role in regulating PMRS activity in erythrocytes. In fact, the effect of iodoacetamide, an alkylating agent that induces depletion of intracellular GSH, was completely counteracted by red wine. Bioactive compounds present in red wine, such as gallic acid, resveratrol, catechin, and quercetin were unable to activate PMRS when tested at the concentrations normally present in aged red wines. On the contrary, the increase of PMRS activity was associated with the anthocyanin fraction, suggesting the capacity of this class of compounds to positively modulate PMRS enzymatic activity. PMID- 26866567 TI - The Relationship Between Endothelial Nitric Oxide Synthase Gene (NOS3) Polymorphisms, NOS3 Expression, and Varicocele. AB - BACKGROUND: Varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. Varicocele is the most common cause of secondary male infertility. Nitric oxide (NO), which has a role on varicocele pathophysiology, is synthesized by endothelial nitric oxide synthase gene (NOS3). OBJECTIVE: In our study, we aimed to explain the relationship between varicocele, three common NOS3 polymorphisms (T-786C, G894T, 4b/a), and NOS3 mRNA expression levels. METHODS: We investigated NOS3 T-786C, G894T, and 4b/a polymorphisms in 102 patients with varicocele and 100 healthy controls. Twenty-four patients and 17 controls were chosen for expression studies based on polymorphism subgroupings. Subgroup 1 includes patients who have no minor allele polymorphisms, and subgroups 2, 3, and 4 have T-786C, G894T, and 4b/a polymorphisms, respectively. RESULTS: The 4b/a polymorphism demonstrated significantly elevated levels in both allele and genotype analysis in the control group compared to the patient group. The G894T polymorphism was statistically elevated for genotypic frequencies in the patient group compared to the control group, but this finding did not extend to allelic frequencies. There were no statistically significant differences in either the allelic or genotypic frequencies between patients and control groups for the T-786C polymorphism. When patient and control expression levels were compared without considering the subgroups, the NOS3 expression level was found to be statistically higher in the patient group. There were no statistically significant differences in the patient and control group expression levels when stratified by subgroup, nor was there any effect of the polymorphisms under study on expression levels. CONCLUSIONS: The 4b/a polymorphism may have a protective effect for varicocelem and G894T polymorphism may contribute to varicocele occurrence by lowering the level of NO. The higher NOS3 expression levels in the patient group may be a kind of dilator compensatory mechanism to protect vascular anatomy in varicocele. PMID- 26866568 TI - Polymorphisms in the type I deiodinase gene and frontal function in recurrent depressive disorder. AB - PURPOSE: Significant impairment of some psychological functions, including cognitive functioning, has been characteristically found in depressed patients. Memory disturbances may be related to the levels of thyroid hormones (TH) that are under the influence of different mechanisms and molecules, including deiodinase type 1(D1) - an important determinant of circulating triiodothyronine (T3). We investigated the relationship between two functionally known polymorphisms within the DIO1 gene, i.e. DIO1a-C/T and DIO1b-A/G, and cognitive functioning in patients diagnosed with recurrent depressive disorder (rDD). In the planned analysis we mainly concentrated on the frontal function: working memory, executive functions and verbal fluency. MATERIALS AND METHODS: Genetic variants were genotyped in 128 patients using a method based on polymerase chain reaction (PCR). Cognitive functions were assessed by the Trail Making Test, the Stroop Test and the Verbal Fluency Test (VFT). RESULTS: No significant associations were found between DIO1 polymorphisms and cognitive functioning in rDD. Only the CT and TT genotypes of the DIO1a variant were significantly related to verbal fluency. There were no significant differences between the distribution of the genotypes and demographic/medical variables. CONCLUSIONS: Based on the study, the examined polymorphisms are not an important risk or protective factor for cognitive impairment in depressive patients. Functional variants within the DIO1 gene that affect triiodothyronine (T3) levels seem not to be associated with cognitive functions. Nevertheless, considering the fact that the DIO1 gene is related to the course and management of depression, further studies on a larger sample size might be suggested. PMID- 26866569 TI - The big five of the monocot genomes. AB - Monocots represent a monophyletic clade of the angiosperms that - based on fossil and molecular records - originated at around the Early Cretaceous from aquatic and wetland ancestors. Among their members are important crops including maize, wheat, rice, sorghum and barley, accounting for the major source for the daily calorie uptake by humans. Reflecting this importance, the partly large and complex genomes of these plants were major targets for ambitious and innovative sequencing projects, which will be discussed in this review article. PMID- 26866570 TI - HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6. AB - CONTEXT: The discrepancies in terms of human leukocyte antigen (HLA)-DRB1-DQA1 DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of the current study is to determine and compare HLA-conferred risks between LADA and T1D. DESIGN: A case-control study was conducted in a representative Chinese data set containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes and for arginine at residue 52 in the DQ-alpha chain or aspartic acid at residue 57 in the DQ-beta chain were analyzed. RESULTS: DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03-DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (odds ratio 2.02 vs 2.20 and 1.61 vs 2.30, respectively). The strongly associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA but confers only half of the T1D risk (odds ratio 2.65 vs 4.84). Interestingly, the most susceptible T1D haplotypes, DRB1*0901 DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201, and DRB1*0301-DQA1*03-DQB1*0303, are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9, and DR9/DR9 are highly associated with T1D susceptibility, whereas only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ-alpha arginine at residue 52-positive, DQ-beta aspartic acid at residue 57-negative, and their combination formed in cis or trans confer susceptibility to T1D but not to LADA. CONCLUSION: Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well. PMID- 26866571 TI - Clinical Relationship Between IgG4-Positive Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma. AB - CONTEXT: Hashimoto's thyroiditis (HT) can be divided into IgG4-positive and IgG4 negative HT. The potential association between IgG4-positive HT and papillary thyroid carcinoma (PTC) remains poorly understood. OBJECTIVE: The aim was to investigate the relationship between IgG4-positive HT and PTC and to compare the prognostic parameters of PTC patients with and without IgG4-positive HT. DESIGN: This was a retrospective study. PATIENTS AND SETTING: A total of 66 HT patients (18 HT-alone, 48 HT with PTC) with serum samples stored before the operation were collected. Another 18 PTC-alone patients were collected as controls. MAIN OUTCOMES: Expression of IgG4, IgG, and TGF-beta1 in thyroid tissues and serum levels of IgG4, TgAb IgG, TgAb IgG4, TPOAb IgG, and TPOAb IgG4 were measured. RESULTS: Seventeen HT patients with PTC (35.4%) were IgG4-positive HT, whereas only one patient (5.6%) was found to be IgG4-positive in the HT-alone group. In contrast, there were only a few IgG4-positive plasma cells in the PTC-alone group. The association of IgG4-positive HT and PTC was statistically significant (P < .05). Moreover, serum levels of TgAb IgG4 and the ratios of TgAb IgG4 to TgAb IgG were significantly higher in the HT with PTC and the PTC-alone groups than in the HT-alone group (P < .05). Furthermore, in the HT with PTC group, the average tumor diameter of 17 IgG4-positive HT with PTC patients was 1.7 +/- 0.8 cm, whereas of 31 IgG4-negative HT patients with PTC, the diameter was 1.2 +/- 0.6 cm (P = .01). A considerably higher percentage of lymph node metastasis (41.2% vs 12.9%; P = .026) was found in PTC patients with IgG4-positive HT as compared with those with IgG4-negative HT. CONCLUSION: PTC may be facilitated by preexisting autoimmune inflammation of IgG4-positive HT. IgG4-positive HT with PTC cases may have worse clinical outcomes. The high levels of TgAb IgG4 might present a risk factor for PTC. PMID- 26866572 TI - Using in situ bacterial communities to monitor contaminants in river sediments. AB - Bacterial communities in sediments of human-impacted rivers are exposed to multiple anthropogenic contaminants and eventually lead to biodiversity lost and ecological functions disable. Nanfei River of Anhui province has been contaminated by pollutants from industrial and/or agricultural sources. This study was conducted to investigate the structure of in situ sediment bacterial communities in Nanfei River and to examine the correlation between the different taxonomic components and contaminant concentrations. The bacterial communities were dominated by Proteobacteria, Bacteroidetes and Chloroflexi. Both the profiles of environmental predictors and the composition of microbial communities differed among agriculture, industrial and confluence regions. There were significant associations between bacterial community phylogenies and the measured contaminants in the sediments. Nutrients (TN and TP) and two metals (Cd and Zn) were negatively correlated with the essential "core" of the bacterial interaction network (Betaproteobacteria and Deltaproteobacteria). Metals (Fe, Ni and Zn) and nutrients (TN and TP) had higher impact on bacterial community compositions than PAHs, OPs and PRTs according to the correlation and network analyses. Furthermore, several sensitive candidate genera were identified as potential bioindicators to monitor key contaminants by species contaminant correlation analysis. Overall, in situ bacterial communities could provide a useful tool for monitoring and assessing ecological stressors in freshwater sediments. PMID- 26866573 TI - Structural Basis for the Interaction between Pyk2-FAT Domain and Leupaxin LD Repeats. AB - Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor tyrosine kinase and belongs to the focal adhesion kinase (FAK) family. Like FAK, the C-terminal focal adhesion-targeting (FAT) domain of Pyk2 binds to paxillin, a scaffold protein in focal adhesions; however, the interaction between the FAT domain of Pyk2 and paxillin is dynamic and unstable. Leupaxin is another member in the paxillin family and was suggested to be the native binding partner of Pyk2; Pyk2 gene expression is strongly correlated with that of leupaxin in many tissues including primary breast cancer. Here, we report that leupaxin interacts with Pyk2-FAT. Leupaxin has four leucine-aspartate (LD) motifs. The first and third LD motifs of leupaxin preferably target the two LD-binding sites on the Pyk2-FAT domain, respectively. Moreover, the full-length leupaxin binds to Pyk2-FAT as a stable one-to-one complex. Together, we propose that there is an underlying selectivity between leupaxin and paxillin for Pyk2, which may influence the differing behavior of the two proteins at focal adhesion sites. PMID- 26866574 TI - Gold Nanorods as Colorful Chromogenic Substrates for Semiquantitative Detection of Nucleic Acids, Proteins, and Small Molecules with the Naked Eye. AB - Herein, we report for the first time a colorful chromogenic substrate, which displays vivid color responses in the presence of different concentration of analytes. Our investigation reveals that the selective shortening of gold nanorods (AuNRs) could generate a series of distinct colors that covers nearly the whole visible range from 400 to 760 nm. These vivid colors can be easily distinguished by the naked eye; as a result, the accuracy of visual inspection could be greatly improved. Next, we demonstrate the utility of AuNRs as multicolor chromogenic substrate to develop a number of colorimetric immunoassay methods, e.g., multicolor enzyme-linked immunosorbent assay (ELISA), multicolor competitive ELISA, and multicolor magnetic immunoassay (MIA). These methods allow us to visually quantify the concentration of a broad range of target molecules with the naked eye, and the obtained results are highly consistent with those state-of-the-art techniques that are tested by the sophisticated apparatus. These multicolor portable and cost-effective immunoassay approaches could be potentially useful for a number of applications, for example, in-home personal healthcare, on-site environmental monitoring, and food inspection in the field. PMID- 26866575 TI - Changes in Neurotransmitter Profiles during Early Zebrafish (Danio rerio) Development and after Pesticide Exposure. AB - During early development, neurotransmitters are important stimulants for the development of the central nervous system. Although the development of different neuronal cell types during early zebrafish (Danio rerio) development is well studied, little is known of the levels of neurotransmitters, their precursors and metabolites during development, and how these levels are affected by exposure to environmental contaminants. A method based on hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry has been applied for the first time to zebrafish embryos and larvae to study five neurotransmitter systems in parallel, including the dopaminergic-andrenergic, glutaminergic-GABAnergic, serotoninergic, histaminergic, and cholinergic systems. Our method enables the quantification of neurotransmitters and their precursors and metabolites in whole zebrafish from the period of zygote to free-swimming larvae 6 days postfertilization (dpf). We observed a developmental stage-dependent pattern with clear differences between the first 2 days of development and the following days. Whereas the neurotransmitter levels steadily increased, the precursors showed a peak at 3 dpf. After exposure to several pesticides, significant differences in concentrations of neurotransmitters and precursors were observed. Our study revealed new insights about neurotransmitter systems during early zebrafish development and showed the usefulness of our approach for environmental neurotoxicity studies. PMID- 26866576 TI - Copper-Catalyzed Alkylation of Nitroalkanes with alpha-Bromonitriles: Synthesis of beta-Cyanonitroalkanes. AB - Copper catalysis now enables the efficient C-alkylation of nitroalkanes with alpha-bromonitriles. Using a simple and inexpensive catalyst, this process provides access to beta-cyanonitroalkanes. The method is highly tolerant of various functional groups and substitution patterns. These functionally dense products serve as orthogonally masked 1,3-diamines, which can be revealed selectively for access to differentially substituted diamines. These products can also be exploited for the formation of complex cyanoalkenes and 5 aminoisoxazoles. PMID- 26866577 TI - Soluble, microporous, Troger's Base copolyimides with tunable membrane performance for gas separation. AB - A facile two-step synthesis beginning with commercial monomers to prepare copolyimides by Troger's Base (TB) formation provides membranes for the first time with tunable gas transport relative to hydrogen separations, CO2 plasticization resistance, and good mechanical and thermal properties. PMID- 26866578 TI - Patients with colorectal cancer associated with Lynch syndrome and MLH1 promoter hypermethylation have similar prognoses. AB - PURPOSE: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is caused by Lynch syndrome (LS) in 3% and sporadic inactivation of MLH1 by hypermethylation (MLH1-hm) in 12% of cases. It is not clear whether outcomes between LS-associated and MLH1-hm CRC differ. The objective of this study was to explore differences in clinical factors and outcomes in these two groups. METHODS: Patients with dMMR CRC identified by immunohistochemistry staining and treated at a single institution from 1998 to 2012 were included. MLH1-hm was established with BRAF mutational analysis or hypermethylation testing. Patients' charts were accessed for information on pathology, germ-line MMR mutation testing, and clinical course. RESULTS: A total of 143 patients had CRC associated with LS (37 patients, 26%) or MLH1-hm (106 patients, 74%). Patients with LS were younger, more often male, presented more often with stage III disease, and had more metachronous disease than patients with MLH1-hm tumors. There was no difference in cancer specific survival (CSS) between the groups; overall survival was longer in patients with LS, but this difference was minimal after adjusting for age and stage at diagnosis. CONCLUSION: CSS did not differ in LS-associated CRC compared with MLH1-hm CRC, suggesting that they carry a similar prognosis.Genet Med 18 9, 863-868. PMID- 26866581 TI - Carbon coated SnO2 nanoparticles anchored on CNT as a superior anode material for lithium-ion batteries. AB - Hierarchically structured carbon coated SnO2 nanoparticles well-anchored on the surface of a CNT (C-SnO2/CNT) material were synthesized by a facile hydrothermal process and subsequent carbonization. The as-obtained C-SnO2/CNT hybrid, when applied as an anode material for lithium ion batteries (LIBs), showed a high reversible capacity up to 1572 mA h g(-1) at 200 mA g(-1) with a superior rate capability (685 mA h g(-1) at 4000 mA g(-1)). Even after 100 charge/discharge cycles at 1000 mA g(-1), a specific capacity of 1100 mA h g(-1) can still be maintained. Such impressive electrochemical performance can be mainly attributed to the hierarchical sandwiched structure and strong synergistic effects of the ultrafine SnO2 nanoparticles and the carbon coating, and thus presents this material a promising anode material for LIBs. PMID- 26866580 TI - The Geisinger MyCode community health initiative: an electronic health record linked biobank for precision medicine research. AB - PURPOSE: Geisinger Health System (GHS) provides an ideal platform for Precision Medicine. Key elements are the integrated health system, stable patient population, and electronic health record (EHR) infrastructure. In 2007, Geisinger launched MyCode, a system-wide biobanking program to link samples and EHR data for broad research use. METHODS: Patient-centered input into MyCode was obtained using participant focus groups. Participation in MyCode is based on opt-in informed consent and allows recontact, which facilitates collection of data not in the EHR and, since 2013, the return of clinically actionable results to participants. MyCode leverages Geisinger's technology and clinical infrastructure for participant tracking and sample collection. RESULTS: MyCode has a consent rate of >85%, with more than 90,000 participants currently and with ongoing enrollment of ~4,000 per month. MyCode samples have been used to generate molecular data, including high-density genotype and exome sequence data. Genotype and EHR-derived phenotype data replicate previously reported genetic associations. CONCLUSION: The MyCode project has created resources that enable a new model for translational research that is faster, more flexible, and more cost effective than traditional clinical research approaches. The new model is scalable and will increase in value as these resources grow and are adopted across multiple research platforms.Genet Med 18 9, 906-913. PMID- 26866579 TI - Oncologists' and cancer patients' views on whole-exome sequencing and incidental findings: results from the CanSeq study. AB - PURPOSE: Although targeted sequencing improves outcomes for many cancer patients, it remains uncertain how somatic and germ-line whole-exome sequencing (WES) will integrate into care. METHODS: We conducted surveys and interviews within a study of WES integration at an academic center to determine oncologists' attitudes about WES and to identify lung and colorectal cancer patients' preferences for learning WES findings. RESULTS: One-hundred sixty-seven patients (85% white, 58% female, mean age 60) and 27 oncologists (22% female) participated. Although oncologists had extensive experience ordering somatic tests (median 100/year), they had little experience ordering germ-line tests. Oncologists intended to disclose most WES results to patients but anticipated numerous challenges in using WES. Patients had moderately low levels of genetic knowledge (mean 4 correct out of 7). Most patients chose to learn results that could help select a clinical trial, pharmacogenetic and positive prognostic results, and results suggesting inherited predisposition to cancer and treatable noncancer conditions (all >=95%). Fewer chose to receive negative prognostic results (84%) and results suggesting predisposition to untreatable noncancer conditions (85%). CONCLUSION: The majority of patients want most cancer-related and incidental WES results. Patients' low levels of genetic knowledge and oncologists' inexperience with large-scale sequencing present challenges to implementing paired WES in practice.Genet Med 18 10, 1011-1019. PMID- 26866582 TI - Enhanced photovoltaic performance of dye-sensitized solar cells using a new photoelectrode material: upconversion YbF3-Ho/TiO2 nanoheterostructures. AB - New up-conversion YbF3-Ho/TiO2 (UC/TiO2) nanoheterostructures are designed and explored as an efficient photoelectrode material to yield dye-sensitized solar cells (DSSCs) with enhanced performance. In this study, we analyze the photogenerated charge transfer properties of the UC/TiO2 nanoheterostructures via surface photovoltage (SPV) and transient photovoltage (TPV) techniques, and the interfacial dynamics of charge transfer and recombination processes in DSSCs using electrochemical impedance spectroscopy (EIS) and open circuit photovoltage decay (OCVD) techniques. It is found that these UC/TiO2 nanoheterostructures combine the upconversion function of YbF3-Ho and the semiconductive merits from TiO2. More importantly, the hetero-junction interface in the UC/TiO2 nanoheterostructures not only induces direct electron-injection from YbF3-Ho to TiO2 by utilizing near-infrared light, but also further improves the existing merits of TiO2 through facilitating the interfacial photoinduced charge separation, suppressing the photoinduced charge recombination and prolonging the lifetimes of excited electrons, which can give further improvement of the photovoltaic performances. When integrating the UC/TiO2 nanoheterostructures into DSSCs, an overall energy conversion efficiency of 8.0% is achieved. There is a 23% enhancement in the overall conversion efficiency and a 19% improvement in the photocurrent, compared to the pristine devices. PMID- 26866583 TI - Portuguese Haemophilia Registry. Set of variables for a computerized solution. AB - National Patient Registries (NPR) have an important role in the management of haemophilia and other inherited bleeding disorders, representing powerful instruments to support healthcare and research. Computer software to assist the NPR is crucial, as it facilitates the introduction of the data from a national universe that will be centralized and merged into a unique location, thus ensuring a greater reliability and accuracy of the collected data, avoiding duplication of patients. In Portugal, despite the efforts and recognition of the need of a NPR, just recently the protocol for the establishment of the computer software to support the Portuguese National Registry of Haemophilia and other Congenital Coagulopathies (PorR H&CC) was approved. This paper aims to present this newly developed computerized solution, as well as to report the main variables and information that will be available. The development of this application, which includes a set of socio-demographic, clinical and treatment data, was based on the principles of WFH, and the database that supports the NPR, with anonymized data, is operated and maintained in accordance with the Data Protection Law. Currently, the first data are available on the application. Our focus now is to ensure more registries and continuous data entry in order to have complete information on the characterization of the haemophilia patient population in Portugal. PMID- 26866584 TI - C2-Symmetric ferrocenyl bisthiazoles: synthesis, photophysical, electrochemical and DFT studies. AB - A series of donor-acceptor ferrocenyl substituted bisthiazoles 3-8 were designed and synthesized by the Pd-catalyzed Suzuki, Heck, and Sonogashira cross-coupling reactions. Their photophysical, electrochemical and computational studies reveal strong donor-acceptor interactions. The photonic and electrochemical studies show that the ferrocenyl bisthiazoles with vinyl linkage ferrocenyl-bisthiazole 4, show better electronic communication compared to rest of the ferrocenyl bisthiazoles. The time dependent density functional theory (TD-DFT) calculation at B3LYP on the ferrocenyl substituted bisthiazoles 3-5 was performed, in which the ferrocenyl-bisthiazole 4 shows strong donor-acceptor interactions compared to the Fc-bisthiazoles 3 and 5. The thermal stability of the ferrocenyl substituted bisthiazoles 3-8 is reported, in which Fc-bisthiazole 8 shows high thermal stability. The single crystal structures of ferrocenyl-bisthiazoles 3 and 5 are reported. PMID- 26866585 TI - 2016 ISBER Annual Meeting and Exhibits in Berlin-"Breaking Down Walls: Unifying Biobanking Communities to Secure Our Sustainability". PMID- 26866586 TI - Distinctive processing in young and older adults: Metacognitive judgments and the isolation paradigm. AB - The isolation paradigm is often used for studying the effects of distinctiveness on memory. Within this paradigm the isolated item can appear early or late in the list. Most prior studies using the isolation paradigm with older adults placed the isolated items late in the study list, however, Smith (2011) used an early isolation list and found that older adults showed an early isolation effect when the dimension of isolation was more readily detected (numbers vs. letters) but did not show an isolation effect when the dimension of difference was more subtle (category membership). The current experiments replicate these findings and demonstrate judgments of learning are elevated for the isolated item in the former case, but not in the latter case, for young and older adults. PMID- 26866587 TI - Aging and associative recognition: A view from the DRYAD model of age-related memory deficits. AB - How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart. PMID- 26866588 TI - DRYAD and ADH: Further comments on explaining age-related differences in memory. AB - Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory. PMID- 26866589 TI - Eye movements and the perceptual span during first- and second-language sentence reading in bilingual older adults. AB - This study addressed a central yet previously unexplored issue in the psychological science of aging, namely, whether the advantages of healthy aging (e.g., greater lifelong experience with language) or disadvantages (e.g., decreases in cognitive and sensory processing) drive L1 and L2 reading performance in bilingual older adults. To this end, we used a gaze-contingent moving window paradigm to examine both global aspects of reading fluency (e.g., reading rates, number of regressions) and the perceptual span (i.e., allocation of visual attention into the parafovea) in bilingual older adults during L1 and L2 sentence reading, as a function of individual differences in current L2 experience. Across the L1 and L2, older adults exhibited reduced reading fluency (e.g., slower reading rates, more regressions), but a similar perceptual span compared with matched younger adults. Also similar to matched younger adults, older adults' reading fluency was lower for L2 reading than for L1 reading as a function of current L2 experience. Specifically, greater current L2 experience increased L2 reading fluency, but decreased L1 reading fluency (for global reading measures only). Taken together, the dissociation between intact perceptual span and impaired global reading measures suggests that older adults may prioritize parafoveal processing despite age-related encoding difficulties. Consistent with this interpretation, post hoc analyses revealed that older adults with higher versus lower executive control were more likely to adopt this strategy. PMID- 26866590 TI - "A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer's Disease Biomarkers": Correction to Levy et al. (2016). AB - Reports an error in "A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer's Disease Biomarkers" by Becca R. Levy, Luigi Ferrucci, Alan B. Zonderman, Martin D. Slade, Juan Troncoso and Susan M. Resnick (Psychology and Aging, Advanced Online Publication, Dec 7, 2015, np). In the article, the correct analyses were reported for bootstrapping; however, the sizes of the bootstrapping samples for Studies 1 and 2 were reversed. (The following abstract of the original article appeared in record 2015-54839-001.) Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. PMID- 26866592 TI - Wolf Lethal Control and Livestock Depredations: Counter-Evidence from Respecified Models. AB - We replicated the study conducted by Wielgus and Peebles (2014) on the effect of wolf mortality on livestock depredations in Montana, Wyoming and Idaho states in the US. Their best models were found to be misspecified due to the omission of the time index and incorrect functional form. When we respecified the models, this replication failed to confirm the magnitude, direction and often the very existence of the original results. Wielgus and Peebles (2014) reported that the increase in the number of wolves culled the previous year would increase the expected number of livestock killed this year by 4 to 6%. But our results showed that the culling of one wolf the previous year would decrease the expected number of cattle killed this year by 1.9%, and the expected number of sheep killed by 3.4%. However, for every wolf killed there is a corresponding 2.2% increase in the expected number of sheep killed in the same year. The increase in sheep depredation appears to be a short term phenomenon. PMID- 26866591 TI - Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle. AB - CUG-BP, Elav-like family member 1 (CELF1) is a highly conserved RNA binding protein that regulates pre-mRNA alternative splicing, polyadenylation, mRNA stability, and translation. In the heart, CELF1 is expressed in the myocardium, where its levels are tightly regulated during development. CELF1 levels peak in the heart during embryogenesis, and aberrant up-regulation of CELF1 in the adult heart has been implicated in cardiac pathogenesis in myotonic dystrophy type 1, as well as in diabetic cardiomyopathy. Either inhibition of CELF activity or over expression of CELF1 in heart muscle causes cardiomyopathy in transgenic mice. Nonetheless, many of the cardiac targets of CELF1 regulation remain unknown. In this study, to identify cardiac targets of CELF1 we performed cross-linking immunoprecipitation (CLIP) for CELF1 from embryonic day 8 chicken hearts. We identified a previously unannotated exon in MYH7B as a novel target of CELF1 mediated regulation. We demonstrated that knockdown of CELF1 in primary chicken embryonic cardiomyocytes leads to increased inclusion of this exon and decreased MYH7B levels. We also investigated global changes in the transcriptome of primary embryonic cardiomyocytes following CELF1 knockdown in a published RNA-seq dataset. Pathway and network analyses identified strong associations between CELF1 and regulation of cell cycle and translation. Important regulatory proteins, including both RNA binding proteins and a cardiac transcription factor, were affected by loss of CELF1. Together, these data suggest that CELF1 is a key regulator of cardiomyocyte gene expression. PMID- 26866593 TI - Comparison of Cervical Spine Anatomy in Calves, Pigs and Humans. AB - BACKGROUND CONTEXT: Animals are commonly used to model the human spine for in vitro and in vivo experiments. Many studies have investigated similarities and differences between animals and humans in the lumbar and thoracic vertebrae. However, a quantitative anatomic comparison of calf, pig, and human cervical spines has not been reported. PURPOSE: To compare fundamental structural similarities and differences in vertebral bodies from the cervical spines of commonly used experimental animal models and humans. STUDY DESIGN: Anatomical morphometric analysis was performed on cervical vertebra specimens harvested from humans and two common large animals (i.e., calves and pigs). METHODS: Multiple morphometric parameters were directly measured from cervical spine specimens of twelve pigs, twelve calves and twelve human adult cadavers. The following anatomical parameters were measured: vertebral body width (VBW), vertebral body depth (VBD), vertebral body height (VBH), spinal canal width (SCW), spinal canal depth (SCD), pedicle width (PW), pedicle depth (PD), pedicle inclination (PI), dens width (DW), dens depth (DD), total vertebral width (TVW), and total vertebral depth (TVD). RESULTS: The atlantoaxial (C1-2) joint in pigs is similar to that in humans and could serve as a human substitute. The pig cervical spine is highly similar to the human cervical spine, except for two large transverse processes in the anterior regions ofC4-C6. The width and depth of the calf odontoid process were larger than those in humans. VBW and VBD of calf cervical vertebrae were larger than those in humans, but the spinal canal was smaller. Calf C7 was relatively similar to human C7, thus, it may be a good substitute. CONCLUSION: Pig cervical vertebrae were more suitable human substitutions than calf cervical vertebrae, especially with respect to C1, C2, and C7. The biomechanical properties of nerve vascular anatomy and various segment functions in pig and calf cervical vertebrae must be considered when selecting an animal model for research on the spine. PMID- 26866594 TI - Serum Taurine and Stroke Risk in Women: A Prospective, Nested Case-Control Study. AB - BACKGROUND: Taurine (2-aminoethanesulfonic acid), a conditionally essential sulfur-containing amino acid, is mainly obtained from diet in humans. Experimental studies have shown that taurine's main biological actions include bile salt conjugation, blood pressure regulation, anti-oxidation, and anti inflammation. METHODS: We conducted a prospective case-control study nested in the New York University Women's Health Study, a cohort study involving 14,274 women enrolled since 1985. Taurine was measured in pre-diagnostic serum samples of 241 stroke cases and 479 matched controls. RESULTS: There was no statistically significant association between serum taurine and stroke risk in the overall study population. The adjusted ORs for stroke were 1.0 (reference), 0.87 (95% CI, 0.59-1.28), and 1.03 (95% CI, 0.69-1.54) in increasing tertiles of taurine (64.3 126.6, 126.7-152.9, and 153.0-308.5 nmol/mL, respectively). A significant inverse association between serum taurine and stroke risk was observed among never smokers, with an adjusted OR of 0.66 (95% CI, 0.37-1.18) and 0.50 (95% CI, 0.26 0.94) for the second and third tertile, respectively (p for trend = 0.01), but not among past or current smokers (p for interaction < 0.01). CONCLUSIONS: We observed no overall association between serum taurine and stroke risk, although a protective effect was observed in never smokers, which requires further investigation. Taurine, Stroke, Epidemiology, Prospective, Case-control study, NYUWHS. PMID- 26866596 TI - Nanotopography-Induced Structural Anisotropy and Sarcomere Development in Human Cardiomyocytes Derived from Induced Pluripotent Stem Cells. AB - Understanding the phenotypic development of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a prerequisite to advancing regenerative cardiac therapy, disease modeling, and drug screening applications. Lack of consistent hiPSC-CM in vitro data can be largely attributed to the inability of conventional culture methods to mimic the structural, biochemical, and mechanical aspects of the myocardial niche accurately. Here, we present a nanogrid culture array comprised of nanogrooved topographies, with groove widths ranging from 350 to 2000 nm, to study the effect of different nanoscale structures on the structural development of hiPSC-CMs in vitro. Nanotopographies were designed to have a biomimetic interface, based on observations of the oriented myocardial extracellular matrix (ECM) fibers found in vivo. Nanotopographic substrates were integrated with a self-assembling chimeric peptide containing the Arg-Gly-Asp (RGD) cell adhesion motif. Using this platform, cell adhesion to peptide-coated substrates was found to be comparable to that of conventional fibronectin-coated surfaces. Cardiomyocyte organization and structural development were found to be dependent on the nanotopographical feature size in a biphasic manner, with improved development achieved on grooves in the 700-1000 nm range. These findings highlight the capability of surface-functionalized, bioinspired substrates to influence cardiomyocyte development, and the capacity for such platforms to serve as a versatile assay for investigating the role of topographical guidance cues on cell behavior. Such substrates could potentially create more physiologically relevant in vitro cardiac tissues for future drug screening and disease modeling studies. PMID- 26866597 TI - Short-Range Temporal Interactions in Sleep; Hippocampal Spike Avalanches Support a Large Milieu of Sequential Activity Including Replay. AB - Hippocampal neural systems consolidate multiple complex behaviors into memory. However, the temporal structure of neural firing supporting complex memory consolidation is unknown. Replay of hippocampal place cells during sleep supports the view that a simple repetitive behavior modifies sleep firing dynamics, but does not explain how multiple episodes could be integrated into associative networks for recollection during future cognition. Here we decode sequential firing structure within spike avalanches of all pyramidal cells recorded in sleeping rats after running in a circular track. We find that short sequences that combine into multiple long sequences capture the majority of the sequential structure during sleep, including replay of hippocampal place cells. The ensemble, however, is not optimized for maximally producing the behavior-enriched episode. Thus behavioral programming of sequential correlations occurs at the level of short-range interactions, not whole behavioral sequences and these short sequences are assembled into a large and complex milieu that could support complex memory consolidation. PMID- 26866598 TI - Non-monotonic Temporal-Weighting Indicates a Dynamically Modulated Evidence Integration Mechanism. AB - Perceptual decisions are thought to be mediated by a mechanism of sequential sampling and integration of noisy evidence whose temporal weighting profile affects the decision quality. To examine temporal weighting, participants were presented with two brightness-fluctuating disks for 1, 2 or 3 seconds and were requested to choose the overall brighter disk at the end of each trial. By employing a signal-perturbation method, which deploys across trials a set of systematically controlled temporal dispersions of the same overall signal, we were able to quantify the participants' temporal weighting profile. Results indicate that, for intervals of 1 or 2 sec, participants exhibit a primacy-bias. However, for longer stimuli (3-sec) the temporal weighting profile is non monotonic, with concurrent primacy and recency, which is inconsistent with the predictions of previously suggested computational models of perceptual decision making (drift-diffusion and Ornstein-Uhlenbeck processes). We propose a novel, dynamic variant of the leaky-competing accumulator model as a potential account for this finding, and we discuss potential neural mechanisms. PMID- 26866600 TI - Complementary Therapies and Medicines and Reproductive Medicine. AB - Complementary therapies and medicines are a broad and diverse range of treatments, and are frequently used by women and their partners during the preconception period to assist with infertility, and to address pregnancy-related conditions. Despite frequent use, the evidence examining the efficacy, effectiveness, and safety for many modalities is lacking, with variable study quality. In this article, we provide an overview of research evidence with the aim of examining the evidence to inform clinical practice. During the preconception period, there is mixed evidence for acupuncture to improve ovulation, or increase pregnancy rates. Acupuncture may improve sperm quality, but there is insufficient evidence to determine whether this results in improved pregnancy and live birth rates. Acupuncture can be described as a low-risk intervention. Chinese and Western herbal medicines may increase pregnancy rates; however, study quality is low. The evaluation of efficacy, effectiveness, and safety during the first trimester of pregnancy has most commonly reported on herbs, supplements, and practices such as acupuncture. There is high-quality evidence reporting the benefits of herbal medicines and acupuncture to treat nausea in pregnancy. The benefit from ginger to manage symptoms of nausea in early pregnancy is incorporated in national clinical guidelines, and vitamin B6 is recommended as a first-line treatment for nausea and vomiting in pregnancy. The safety of ginger and vitamin B6 is considered to be well established, and is based on epidemiological studies. Acupuncture has been shown to reduce back pain and improve function for women in early pregnancy. There is little evidence to support the use of cranberries in pregnancy for prevention of urinary tract infections, and chiropractic treatment for back pain. Overall the numbers of studies are small and of low quality, although the modalities appear to be low risk of harm. PMID- 26866599 TI - No Fabry Disease in Patients Presenting with Isolated Small Fiber Neuropathy. AB - OBJECTIVE: Screening for Fabry disease in patients with small fiber neuropathy has been suggested, especially since Fabry disease is potentially treatable. However, the diagnostic yield of testing for Fabry disease in isolated small fiber neuropathy patients has never been systematically investigated. Our aim is to determine the presence of Fabry disease in patients with small fiber neuropathy. METHODS: Patients referred to our institute, who met the criteria for isolated small fiber neuropathy were tested for Fabry disease by measurement of alpha-Galactosidase A activity in blood, lysosomal globotriaosylsphingosine in urine and analysis on possible GLA gene mutations. RESULTS: 725 patients diagnosed with small fiber neuropathy were screened for Fabry disease. No skin abnormalities were seen except for redness of the hands or feet in 30.9% of the patients. Alfa-Galactosidase A activity was tested in all 725 patients and showed diminished activity in eight patients. Lysosomal globotriaosylsphingosine was examined in 509 patients and was normal in all tested individuals. Screening of GLA for mutations was performed for 440 patients, including those with diminished alpha-Galactosidase A activity. Thirteen patients showed a GLA gene variant. One likely pathogenic variant was found in a female patient. The diagnosis Fabry disease could not be confirmed over time in this patient. Eventually none of the patients were diagnosed with Fabry disease. CONCLUSIONS: In patients with isolated small fiber neuropathy, and no other signs compatible with Fabry disease, the diagnostic yield of testing for Fabry disease is extremely low. Testing for Fabry disease should be considered only in cases with additional characteristics, such as childhood onset, cardiovascular disease, renal failure, or typical skin lesions. PMID- 26866601 TI - Diagnostic Criteria and Treatment for Gestational Diabetes Mellitus. AB - The prevalence of gestational diabetes mellitus (GDM) is high, and the risks of maternal and perinatal complications with clear hyperglycemia are well recognized. The worldwide obesity epidemic and the consequent excess of hyperglycemia have resulted in a rising prevalence of GDM. Changing definitions and more intensive screening may also be contributing to an increased prevalence. Despite the recognized risks, much controversy surrounds the screening, diagnosis, and treatment of GDM. The more stringent diagnostic criteria, advocated in new guidelines, are based on observational studies and are not guided by interventional studies. Here, we review the evidence behind updated diagnostic criteria, stricter treatment targets, and current controversies and conclude that international consensus regarding diagnosis and treatment will only be achieved with further evidence from interventional studies. PMID- 26866602 TI - Evaluation and Verification of Channel Transmission Characteristics of Human Body for Optimizing Data Transmission Rate in Electrostatic-Coupling Intra Body Communication System: A Comparative Analysis. AB - BACKGROUND: Intra-body communication is a new wireless scheme for transmitting signals through the human body. Understanding the transmission characteristics of the human body is therefore becoming increasingly important. Electrostatic coupling intra-body communication system in a ground-free situation that integrate electronic products that are discretely located on individuals, such as mobile phones, PDAs, wearable computers, and biomedical sensors, are of particular interest. MATERIALS AND METHODS: The human body is modeled as a simplified Resistor-Capacitor network. A virtual ground between the transmitter and receiver in the system is represented by a resister-capacitor network. Value of its resistance and capacitance are determined from a system perspective. The system is characterized by using a mathematical unit step function in digital baseband transmission scheme with and without Manchester code. As a result, the signal-to-noise and to-intersymbol-interference ratios are improved by manipulating the load resistor. The data transmission rate of the system is optimized. A battery-powered transmitter and receiver are developed to validate the proposal. RESULTS: A ground-free system fade signal energy especially for a low-frequency signal limited system transmission rate. The system transmission rate is maximized by simply manipulating the load resistor. Experimental results demonstrate that for a load resistance of 10k-50k Omega, the high-pass 3 dB frequency of the band-pass channel is 400kHz-2MHz in the worst-case scenario. The system allows a Manchester-coded baseband signal to be transmitted at speeds of up to 20M bit per second with signal-to-noise and signal-to-intersymbol interference ratio of more than 10 dB. CONCLUSION: The human body can function as a high speed transmission medium with a data transmission rate of 20Mbps in an electrostatic-coupling intra-body communication system. Therefore, a wideband signal can be transmitted directly through the human body with a good signal-to noise quality of 10 dB if the high-pass 3 dB frequency is suitably selected. PMID- 26866603 TI - Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans. AB - OBJECTIVE: Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia. RESEARCH DESIGN AND METHODS: We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist. RESULTS: In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels. CONCLUSIONS: In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency. PMID- 26866604 TI - Oxazolines as Dual-Function Traceless Chromophores and Chiral Auxiliaries: Enantioselective Photoassisted Synthesis of Polyheterocyclic Ketones. AB - 2-(o-Amidophenyl)oxa- and -thiazolines undergo excited-state intramolecular proton transfer (ESIPT), generating aza-o-xylylenes capable of intramolecular [4+2] and [4+4] cycloadditions with tethered unsaturated pendants. Facile hydrolysis of the primary photoproducts, spiro-oxazolidines and thiazolidines, under mild conditions unmasks a phenone functionality. Variations in linkers allow for access to diverse core scaffolds in the primary photoproducts, rendering the approach compatible with the philosophy of diversity-oriented synthesis. Chiral oxazolines, readily available from the corresponding amino alcohols, yield enantioenriched keto-polyheterocycles of complex topologies with enantiomeric excess values up to 90%. PMID- 26866605 TI - Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0. AB - EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting. PMID- 26866606 TI - Cryptanalysis and Improvement of a Biometric-Based Multi-Server Authentication and Key Agreement Scheme. AB - With the security requirements of networks, biometrics authenticated schemes which are applied in the multi-server environment come to be more crucial and widely deployed. In this paper, we propose a novel biometric-based multi-server authentication and key agreement scheme which is based on the cryptanalysis of Mishra et al.'s scheme. The informal and formal security analysis of our scheme are given, which demonstrate that our scheme satisfies the desirable security requirements. The presented scheme provides a variety of significant functionalities, in which some features are not considered in the most of existing authentication schemes, such as, user revocation or re-registration and biometric information protection. Compared with several related schemes, our scheme has more secure properties and lower computation cost. It is obviously more appropriate for practical applications in the remote distributed networks. PMID- 26866608 TI - Joint analysis of multiple phenotypes: summary of results and discussions from the Genetic Analysis Workshop 19. AB - For Genetic Analysis Workshop 19, 2 extensive data sets were provided, including whole genome and whole exome sequence data, gene expression data, and longitudinal blood pressure outcomes, together with nongenetic covariates. These data sets gave researchers the chance to investigate different aspects of more complex relationships within the data, and the contributions in our working group focused on statistical methods for the joint analysis of multiple phenotypes, which is part of the research field of data integration. The analysis of data from different sources poses challenges to researchers but provides the opportunity to model the real-life situation more realistically.Our 4 contributions all used the provided real data to identify genetic predictors for blood pressure. In the contributions, novel multivariate rare variant tests, copula models, structural equation models and a sparse matrix representation variable selection approach were applied. Each of these statistical models can be used to investigate specific hypothesized relationships, which are described together with their biological assumptions.The results showed that all methods are ready for application on a genome-wide scale and can be used or extended to include multiple omics data sets. The results provide potentially interesting genetic targets for future investigation and replication. Furthermore, all contributions demonstrated that the analysis of complex data sets could benefit from modeling correlated phenotypes jointly as well as by adding further bioinformatics information. PMID- 26866607 TI - The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics. AB - The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes. PMID- 26866610 TI - Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits. AB - BACKGROUND: Caffeine is a commonly used drug for apnea of prematurity. It may, however, also have a beneficial effect on bronchopulmonary dysplasia (BPD), which is the most common complication of extreme preterm birth. OBJECTIVES: To study the inflammatory, structural and functional effects of caffeine in an animal model of BPD. METHODS: Preterm New Zealand-Dendermonde rabbits (gestational day 28; term 31) were randomized to three groups: normoxia-placebo (N-P), hyperoxia placebo (H-P) and hyperoxia-caffeine (H-C). Lung function was assessed on postnatal day 5, along with airway morphometry, vascular morphometry and a score observing airway inflammation. RESULTS: Caffeine improved lung function by increasing lung volume [mean displaced volume N-P: 40.1 +/- 6 ml/kg, H-P: 27.8 +/ 8 ml/kg and H-C: 34.4 +/- 7 ml/kg (p < 0.05); total lung capacity: N-P: 1.17 +/- 0.1 ml, H-P: 0.67 +/- 0.1 ml and H-C: 1.1 +/- 0.1 ml (p < 0.05)], decreasing tissue damping [N-P: 2.7 +/- 0.3 cm H2O/ml, H-P: 4.6 +/- 0.6 cm H2O/ml and H-C: 3.2 +/- 0.4 cm H2O/ml (p < 0.05)], elastance [N-P: 9.3 +/- 2.4 cm H2O/ml, H-P: 19.2 +/- 7.4 cm H2O/ml and H-C: 10.7 +/- 2 cm H2O/ml (p < 0.05)] and compliance [N-P: 0.06 +/- 0.01 cm H2O/ml, H-P: 0.054 +/- 0.01 cm H2O/ml and H-C: 0.07 +/- 0.013 cm H2O/ml (p < 0.05)]. Caffeine also improved histology by decreasing alveolar size [linear intercepts; N-P: 83.6 +/- 1.7, H-P: 82.9 +/- 1.6 and H-C: 67.3 +/- 1.4 (p < 0.05)], increasing radial alveolar count (N-P: 6.6 +/- 0.5, H P: 5.7 +/- 0.6 and H-C: 7.05 +/- 0.5) and decreasing the acute inflammation score [N-P: 0.3 +/- 0.1, H-P: 0.5 +/- 0.1 and H-C: 0.4 +/- 0.1 (p < 0.05)]. CONCLUSION: In preterm rabbits, caffeine reduces the functional, architectural and inflammatory pulmonary changes induced by hyperoxia in the lung. PMID- 26866611 TI - Identification of energy dissipation mechanisms in CNT-reinforced nanocomposites. AB - In this paper we present our recent findings on the mechanisms of energy dissipation in polymer-based nanocomposites obtained through experimental investigations. The matrix of the nanocomposite was polystyrene (PS) which was reinforced with carbon nanotubes (CNTs). To study the mechanical strain energy dissipation of nanocomposites, we measured the ratio of loss to storage modulus for different CNT concentrations and alignments. CNT alignment was achieved via hot-drawing of PS-CNT. In addition, CNT agglomeration was studied via a combination of SEM imaging and Raman scanning. We found that at sufficiently low strains, energy dissipation in composites with high CNT alignment is not a function of applied strain, as no interfacial slip occurs between the CNTs and PS. However, below the interfacial slip strain threshold, damping scales monotonically with CNT content, which indicates the prevalence of CNT-CNT friction dissipation mechanisms within agglomerates. At higher strains, interfacial slip also contributes to energy dissipation. However, the increase in damping with strain, especially when CNT agglomerates are present, does not scale linearly with the effective interface area between CNTs and PS, suggesting a significant contribution of friction between CNTs within agglomerates to energy dissipation at large strains. In addition, for the first time, a comparison between the energy dissipation in randomly oriented and aligned CNT composites was made. It is inferred that matrix plasticity and tearing caused by misorientation of CNTs with the loading direction is a major cause of energy dissipation. The results of our research can be used to design composites with high energy dissipation capability, especially for applications where dynamic loading may compromise structural stability and functionality, such as rotary wing structures and antennas. PMID- 26866609 TI - Desensitization and Incomplete Recovery of Hepatic Target Genes After Chronic Thyroid Hormone Treatment and Withdrawal in Male Adult Mice. AB - Clinical symptoms may vary and not necessarily reflect serum thyroid hormone (TH) levels during acute and chronic hyperthyroidism as well as recovery from hyperthyroidism. We thus examined changes in hepatic gene expression and serum TH/TSH levels in adult male mice treated either with a single T3 (20 MUg per 100 g body weight) injection (acute T3) or daily injections for 14 days (chronic T3) followed by 10 days of withdrawal. Gene expression arrays from livers harvested at these time points showed that among positively-regulated target genes, 320 were stimulated acutely and 429 chronically by T3. Surprisingly, only 69 of 680 genes (10.1%) were induced during both periods, suggesting desensitization of the majority of acutely stimulated target genes. About 90% of positively regulated target genes returned to baseline expression levels after 10 days of withdrawal; however, 67 of 680 (9.9%) did not return to baseline despite normalization of serum TH/TSH levels. Similar findings also were observed for negatively regulated target genes. Chromatin immunoprecipitation analysis of representative positively regulated target genes suggested that acetylation of H3K9/K14 was associated with acute stimulation, whereas trimethylation of H3K4 was associated with chronic stimulation. In an in vivo model of chronic intrahepatic hyperthyroidism since birth, adult male monocarboxylate transporter-8 knockout mice also demonstrated desensitization of most acutely stimulated target genes that were examined. In summary, we have identified transcriptional desensitization and incomplete recovery of gene expression during chronic hyperthyroidism and recovery. Our findings may be a potential reason for discordance between clinical symptoms and serum TH levels observed in these conditions. PMID- 26866612 TI - Factors Associated with Reevaluation of the Stepwise Excavation Procedure: An 8 Year Retrospective Study. AB - Although the stepwise excavation procedure (SWP) has been shown to be an effective caries treatment technique, studies reporting its application outside of controlled clinical trials are limited. We performed a retrospective study from patient record data to assess the proportion of patients who had an SWP reevaluated within 18 months at The University of Iowa College of Dentistry (UICOD) between 2004 and 2012, and evaluated the association between different variables and this outcome. A total of 1,985 SWPs were performed in 1,326 patients, with 518 patients having had reevaluation within 18 months. Bivariate analysis and logistic regression modeling revealed strong associations between explanatory variables such as provider type, tooth type, patient age, number of recalls and the calendar year in which the SWP was done and reevaluation status. There was also evidence of association with dental insurance status. Other characteristics such as gender, distance traveled to the UICOD, number of surfaces treated and tooth arch did not show any significant association. In general, patients were more likely to have reevaluation when seen by faculty members or residents, the procedure was performed in molars/pre-molars, they were older, they had more recalls and were seen earlier in the study period. These results suggest that decisions to use SWP should consider patient demographics and treatment characteristics such as provider level, tooth type, patient age and number of recalls. The impact of treatment year may reflect program heterogeneity or temporal changes in external societal factors. PMID- 26866613 TI - Recommendations in the American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Related to the Use of Biologic Agents in Patients With a History of Cancer Need Reconsideration: Comment on the Article by Singh et al. PMID- 26866618 TI - GaAlAs laser-induced pulp mineralization involves dentin matrix protein 1 and osteopontin expression. AB - OBJECTIVES: GaAlAs lasers induce pulp mineralization by promoting reparative dentinogenesis. This study analyzed the expression of dentin matrix protein 1 (DMP1) and osteopontin in GaAlAs laser-irradiated rat molars, to examine the hypothesis that these proteins play a role in the laser-induced reparative dentinogenic process. MATERIALS AND METHODS: The mesial surfaces of the upper first molars of 8-week-old Wistar rats were irradiated with a pulsed GaAlAs laser. After 1-14 days, mRNA expression of DMP1 and osteopontin in the coronal pulp was analyzed using real-time PCR. DMP1, osteopontin, and heat shock protein 25 (HSP25) were immunolocalized at 1-21 days. RESULTS: The pulp exhibited a degenerative zone in its mesial portion on days 1-3, and progressive formation of reparative dentin lined with HSP25-immunoreactive odontoblast-like cells, from day 7 onwards. DMP1 and osteopontin mRNA expression were significantly upregulated on days 1-7 and 3-7, respectively. From day 7 onwards, DMP1 and osteopontin immunoreactivity colocalized along the boundary between the primary and reparative dentin. CONCLUSION: GaAlAs laser irradiation of rat molars induced upregulated DMP1 and osteopontin mRNA expression in the coronal pulp, followed by the formation of reparative dentin and the colocalization of DMP1 and osteopontin immunoreactivity at the site at which this tissue first appeared. PMID- 26866621 TI - Spatioselective Electrochemical and Photoelectrochemical Functionalization of Silicon Microwires with Axial p/n Junctions. AB - The spatioselective functionalization of silicon microwires with axial p/n junctions is achieved using the electronic properties of the junction. (Photo)electrochemical deposition of metals is demonstrated at the bottom and top of the wires in the dark and light, respectively. The junction depletion layer remains unmodified, which allows its visualization and comparison with theoretical calculations. PMID- 26866627 TI - Bone marrow segmentation based on a combined consideration of transverse relaxation processes and Dixon oscillations. AB - The aim of this study was to demonstrate that gradient-echo sampling of single spin echoes can be used to isolate the signal from trabecular bone marrow, with high-quality segmentation and surface reconstructions resulting from the application of simple post-processing strategies. Theoretical expressions of the time-domain single-spin-echo signal were used to simulate signals from bone marrow, non-bone fatty deposits and muscle. These simulations were compared with and used to interpret signals obtained by the application of the gradient-echo sampling of a spin-echo sequence to image the knee and surrounding tissues at 1.5 T. Trabecular bone marrow has a much higher reversible transverse relaxation rate than surrounding non-bone fatty deposits and other musculoskeletal tissues. This observation, combined with a choice of gradient-echo spacing that accentuates Dixon-type oscillations from chemical-shift interference effects, enabled the isolation of bone marrow signal from surrounding tissues through the use of simple image subtraction and thresholding. Three-dimensional renderings of the marrow surface were then readily generated with this approach - renderings that may prove useful for bone morphology assessment, e.g. for the measurement of femoral anteversion. In conclusion, understanding the behavior of signals from bone marrow and surrounding tissue as a function of time through a spin echo facilitates the segmentation and reconstruction of bone marrow surfaces using straightforward post-processing strategies that are typically available on modern radiology workstations. PMID- 26866626 TI - Aging Promotes Sirtuin 3-Dependent Cartilage Superoxide Dismutase 2 Acetylation and Osteoarthritis. AB - OBJECTIVE: To quantify functional age-related changes in the cartilage antioxidant network in order to discover novel mediators of cartilage oxidative stress and osteoarthritis (OA) pathophysiology. METHODS: We evaluated histopathologic changes of knee OA in 10-, 20-, and 30-month-old male F344BN rats and analyzed cartilage oxidation according to the ratio of reduced to oxidized glutathione. Antioxidant gene expression and protein abundance were analyzed by quantitative reverse transcription-polymerase chain reaction and selected reaction-monitoring mass spectrometry, respectively. Superoxide dismutase 2 (SOD2) activity and acetylation were analyzed by colorimetric enzyme assays and Western blotting, respectively. We examined human OA cartilage to evaluate the clinical relevance of SOD2 acetylation, and we tested age-related changes in the mitochondrial deacetylase sirtuin 3 (SIRT-3) in rats and mice. RESULTS: Cartilage oxidation and OA severity in F344BN rats increased with age and were associated with an increase in SOD2 expression and protein abundance. However, SOD2-specific activity decreased with age due to elevated posttranslational lysine acetylation. Consistent with these findings, SIRT-3 levels decreased substantially with age, and treatment with SIRT-3 increased SOD2 activity in an age-dependent manner. SOD2 was also acetylated in human OA cartilage, and activity was increased with SIRT-3 treatment. Moreover, in C57BL/6J mice, cartilage SIRT-3 expression decreased with age, and whole-body deletion of SIRT-3 accelerated the development of knee OA. CONCLUSION: Our results show that SIRT-3 mediates age-related changes in cartilage redox regulation and protects against early-stage OA. These findings suggest that mitochondrial acetylation promotes OA and that restoration of SIRT-3 in aging cartilage may improve cartilage resistance to oxidative stress by rescuing acetylation-dependent inhibition of SOD2 activity. PMID- 26866628 TI - Association of plasma chloride values with acute kidney injury in the critically ill - a prospective observational study. AB - BACKGROUND: Chloride-rich fluids have been found to associate with an increased risk for acute kidney injury (AKI) among intensive care unit (ICU) patients. Studies evaluating the association of plasma chloride (Cl) with the development of AKI are few. We hypothesized that higher plasma Cl is associated with an increased risk for the development of AKI. METHODS: In this sub-study of the prospective FINNAKI study, we analyzed Cl values measured during ICU stay in two ICUs at a tertiary center including 445 patients. We calculated time-weighted mean values within the first 24 h in ICU for plasma Cl (ClTWM 24 ). We analyzed the association of ClTWM 24 primarily with the development of AKI, and secondarily with 90-day mortality. RESULTS: Based on the first measured Cl value, 350 of 445 patients [78.7 (95 CI, 74.8-82.5)] had hyperchloremia (P-Cl > 106 mmol/l) and 48 [10.8 (95 CI, 7.9-13.7)] severe hyperchloremia (P-Cl > 114 mmol/l). Altogether 217 of 445 [48.8% (95% CI 44.2-53.4%)] patients developed AKI. Of these 217, AKI was diagnosed in 62 (28.6%) after 24 h from ICU admission and were included in the analysis regarding development of AKI. ClTWM 24 was associated with an increased risk for the development of AKI (OR1.099; 1.003 1.205) after multivariable adjustments. According to ClTWM 24 , no difference in 90-day mortality between severely hyperchloremic patients and others existed. CONCLUSIONS: More than three of four critically ill patients had hyperchloremia and 1 of 10 had its severe form. Higher time-weighted mean chloride was independently associated with an increased risk for AKI. PMID- 26866630 TI - Prevention of Incident Knee Osteoarthritis by Moderate Weight Loss in Overweight and Obese Females. AB - OBJECTIVE: This study evaluated the effect of moderate weight loss on the incidence of knee osteoarthritis (OA) in middle-aged overweight and obese women, without clinical and radiologic knee OA at baseline. METHODS: A total of 353 women (87%) with followup data available were selected from the Prevention of Knee Osteoarthritis in Overweight Females study, which evaluated the preventive effect of a diet and exercise intervention and of oral glucosamine sulfate on the incidence of knee OA. This was an exploratory proof-of-concept analysis, which compared the incidence of knee OA between women who reached the clinically relevant weight loss target of 5 kg or 5% of body weight after 30 months and those who did not reach this target. RESULTS: The weight loss group showed a significantly lower incidence of knee OA according to the primary outcome measure, which was composed of the American College of Rheumatology criteria (clinical and radiographic), Kellgren/Lawrence grade >=2, and joint space narrowing >=1.0 mm (15% versus 20%; odds ratio 0.5, 95% confidence interval 0.3 0.9). Moreover, the weight loss also positively affected several health measures, such as blood glucose level, body fat percentage, and blood pressure. CONCLUSION: A reduction of >=5 kg or 5% of body weight over a 30-month period reduces the risk for the onset of radiographic knee OA in middle-aged overweight and obese women. Because of the slow progression of the disease, a longer followup period will be necessary before the number of prevented cases of knee OA by moderate weight loss becomes clinically more relevant. PMID- 26866629 TI - Using family members to augment genetic case-control studies of a life threatening disease. AB - Survival bias is difficult to detect and adjust for in case-control genetic association studies but can invalidate findings when only surviving cases are studied and survival is associated with the genetic variants under study. Here, we propose a design where one genotypes genetically informative family members (such as offspring, parents, and spouses) of deceased cases and incorporates that surrogate genetic information into a retrospective maximum likelihood analysis. We show that inclusion of genotype data from first-degree relatives permits unbiased estimation of genotype association parameters. We derive closed-form maximum likelihood estimates for association parameters under the widely used log additive and dominant association models. Our proposed design not only permits a valid analysis but also enhances statistical power by augmenting the sample with indirectly studied individuals. Gene variants associated with poor prognosis can also be identified under this design. We provide simulation results to assess performance of the methods. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26866631 TI - Factors to consider when applying transcranial magnetic stimulation of dorsolateral prefrontal cortex when resting motor threshold is asymmetric: A case study. AB - Transcranial magnetic stimulation (TMS) is an increasingly popular tool in treating psychiatric conditions. The dorsal lateral prefrontal cortex (DLPFC) is typically targeted for stimulation, with magnetic field intensity being calibrated by establishing resting motor threshold (RMT) at hand region of primary motor cortex (M1 hand). This presumes that scalp-to-cortex distance (SCD) and cortical thickness is similar at both sites. We present data from a patient who had very asymmetrical RMTs (47 and 78). We investigated SCDs in this patient at the M1 hand and DLPFC, and the M1 hand cortical thickness. We also investigated TMS electric field distribution. The M1 hand SCD and cortical thickness of the M1 hand was larger on the side with higher RMT. Electric field finite element modelling demonstrated the focal point did not effectively reach the M1 hand with higher RMT as the postcentral gyrus was shunting it. Hence, successful DLPFC treatment was based upon the side with lower RMT. This study highlights the importance of tailoring DLPFC treatment intensity not only based on RMT at the M1 hand, and upon the degree to which SCD distance differs between sites, but also based upon size, shape, and density of M1 hand, as well as electric field distribution. PMID- 26866632 TI - Clairvoyance. PMID- 26866633 TI - Two Phenotypes Are Identified by Cluster Analysis in Early Inflammatory Back Pain Suggestive of Spondyloarthritis: Results From the DESIR Cohort. AB - OBJECTIVE: To determine whether disease manifestations at baseline would combine according to distinguishable ordered phenotypes in patients with early inflammatory back pain (IBP) suggestive of spondyloarthritis (SpA). METHODS: Baseline clinical and demographic characteristics as well as imaging features and biologic data on patients included in the French multicenter Devenir des Spondyloarthropathies Indiffererenciees Recentes cohort were analyzed by multiple correspondence analysis and cluster analysis to identify subgroups of patients based on shared characteristics. RESULTS: Cluster analysis allowed us to classify the 679 patients with no missing data into 2 major groups-one with a predominance of isolated axial manifestations and the other with associated peripheral symptoms. The application of the same analysis to selected subsets of the cohort, such as HLA-B27-positive and -negative patients and patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axial SpA, resulted again in an optimal division of the samples into 2 recurrent clusters of patients similar to those observed in the whole cohort. CONCLUSION: Cluster analysis of SpA manifestations among patients with early IBP highly suggestive of SpA allowed us to clearly identify at baseline 2 different clinical phenotypes-one with predominant axial manifestations and the other with predominant peripheral manifestations. Ongoing follow-up will allow us to determine whether these clusters correspond to different patterns of disease severity. PMID- 26866636 TI - Leukodystrophies and genetic leukoencephalopathies in childhood: a national epidemiological study. AB - AIM: To report on the epidemiology of the brain white matter disorders of children identified via a national prospective study. METHOD: Since 1997 a study of UK children with progressive intellectual and neurological deterioration (PIND) has used the British Paediatric Surveillance Unit system to identify children with progressive neurodegenerative disease. This paper reports on children in the study with brain white matter disorders. RESULTS: Between May 1997 and November 2014 the PIND study identified 349 children with diagnosed leukodystrophies, giving an estimated UK lifetime risk of 31/million live births. There were 18 specific diseases in the group and relatively large numbers of affected children came from consanguineous Pakistani families. In addition there were 454 children with genetic leukoencephalopathies - in this group there were 38 diseases. 5.8% of children with scan evidence of brain white matter disorders did not receive a specific diagnosis. INTERPRETATION: These unique prospectively obtained national data avoid the selection bias inherent in reports from single centres. White matter disorders of the central nervous system comprise more than half of UK paediatric neurodegenerative diseases meeting the PIND criteria. This paper reports the lifetime risk/million live births for the commonest leukodystrophies, providing a basis for comparison with future studies. PMID- 26866635 TI - Wnt/beta-Catenin Signaling Determines the Vasculogenic Fate of Postnatal Mesenchymal Stem Cells. AB - Vasculogenesis is the process of de novo blood vessel formation observed primarily during embryonic development. Emerging evidence suggest that postnatal mesenchymal stem cells are capable of recapitulating vasculogenesis when these cells are engaged in tissue regeneration. However, the mechanisms underlining the vasculogenic differentiation of mesenchymal stem cells remain unclear. Here, we used stem cells from human permanent teeth (dental pulp stem cells [DPSC]) or deciduous teeth (stem cells from human exfoliated deciduous teeth [SHED]) as models of postnatal primary human mesenchymal stem cells to understand mechanisms regulating their vasculogenic fate. GFP-tagged mesenchymal stem cells seeded in human tooth slice/scaffolds and transplanted into immunodeficient mice differentiate into human blood vessels that anastomize with the mouse vasculature. In vitro, vascular endothelial growth factor (VEGF) induced the vasculogenic differentiation of DPSC and SHED via potent activation of Wnt/beta catenin signaling. Further, activation of Wnt signaling is sufficient to induce the vasculogenic differentiation of postnatal mesenchymal stem cells, while Wnt inhibition blocked this process. Notably, beta-catenin-silenced DPSC no longer differentiate into endothelial cells in vitro, and showed impaired vasculogenesis in vivo. Collectively, these data demonstrate that VEGF signaling through the canonical Wnt/beta-catenin pathway defines the vasculogenic fate of postnatal mesenchymal stem cells. Stem Cells 2016;34:1576-1587. PMID- 26866639 TI - Androgens in polycystic ovary syndrome: lessons from experimental models. AB - PURPOSE OF REVIEW: There is substantial evidence to support a role for androgens acting via the androgen receptor in the development of the pathological disorder, polycystic ovary syndrome (PCOS). PCOS is the most common endocrine condition in women, but its etiology remains unknown. This review focuses on how animal experimental models of PCOS are providing strong evidence to support hyperandrogenism as an important mediator in the development of PCOS characteristics. RECENT FINDINGS: A variety of animal models for PCOS have now been established by increasing androgen exposure, supporting a role for androgens in the pathogenesis of PCOS. However, some androgens can be aromatized into estrogens leading to confusion on which PCOS traits are primary mediated via androgenic (mediated via the androgen receptor) or estrogenic (mediated via the estrogen receptor) mechanisms. Recent findings from studies comparing the induction of PCOS by aromatizable and nonaromatizable androgens, as well as androgen receptor knockout mouse models have enhanced our understanding of the mechanisms underlying PCOS, and verify that androgen receptor-mediated actions play a key role in the development of PCOS. SUMMARY: Animal models have provided strong evidence to support that androgen receptor-mediated actions are key mediators in the development of PCOS traits. PMID- 26866638 TI - Dependency and self-criticism in treatments for depression. AB - Dependency and self-criticism are vulnerability factors for depression. How these personality factors change with treatment for depression and how they relate to symptom change across different types of treatment require further research. In addition, cultural differences that interact with the dependency/self-criticism depression relation remain underinvestigated. We randomly assigned 149 adults with major depression to receive active medication (MED; n = 50), supportive expressive therapy (SET; n = 49), or placebo pill (PBO; n = 50). Participants completed the Depressive Experiences Questionnaire (DEQ; Blatt, D'Afflitti, & Quinlan, 1976) before and after treatment and completed the Hamilton Rating Scale for Depression (Hamilton, 1967) throughout the course of treatment. Self criticism as measured on the DEQ decreased with treatment similarly across conditions. DEQ Dependency decreased in MED but remained unchanged in SET and PBO. Higher initial dependency, but not higher initial self-criticism, predicted poor treatment response across conditions. Greater reduction in self-criticism was associated with greater reduction in depressive symptoms, but the effect was weaker for racial minorities (vs. White). Increase in connectedness, an adaptive form of dependency, was associated with symptom improvement in SET but not MED. Hence, different pathways of change seem to be implicated in the treatment of depression depending on culture and type of intervention. Implications for future research are discussed. (PsycINFO Database Record PMID- 26866637 TI - Discriminatory experiences associated with posttraumatic stress disorder symptoms among transgender adults. AB - Discrimination has been shown to disproportionately burden transgender people; however, there has been a lack of clinical attention to the mental health sequelae of discrimination, including posttraumatic stress disorder (PTSD) symptoms. Additionally, few studies contextualize discrimination alongside other traumatic stressors in predicting PTSD symptomatology. The current study sought to fill these gaps. A community-based sample of 412 transgender adults (mean age 33, SD = 13; 63% female-to-male spectrum; 19% people of color; 88% sampled online) completed a cross-sectional self-report survey of everyday discrimination experiences and PTSD symptoms. Multivariable linear regression models examined the association between self-reported everyday discrimination experiences, number of attributed domains of discrimination, and PTSD symptoms, adjusting for prior trauma, sociodemographics, and psychosocial comorbidity. The mean number of discrimination attributions endorsed was 4.8 (SD = 2.4) and the 5 most frequently reported reasons for discrimination were: gender identity and/or expression (83%), masculine and feminine appearance (79%), sexual orientation (68%), sex (57%), and age (44%). Higher everyday discrimination scores (beta = 0.25; 95% CL [0.21, 0.30]) and greater number of attributed reasons for discrimination experiences (beta = 0.05; 95% CL [0.01, 0.10]) were independently associated with PTSD symptoms, even after adjusting for prior trauma experiences. Everyday discrimination experiences from multiple sources necessitate clinical consideration in treatment for PTSD symptoms in transgender people. (PsycINFO Database Record PMID- 26866640 TI - Treatment of Unstable Slipped Capital Epiphysis Via the Modified Dunn Procedure. AB - BACKGROUND: The modified Dunn procedure has been shown to be safe and effective in treating unstable slipped capital femoral epiphysis (SCFE). We present a consecutive series of unstable SCFE managed by a single surgeon with a focus on timing of surgical intervention, postoperative complications, and radiographic results. METHODS: Thirty-one consecutive unstable SCFEs were treated. Demographics, presentation time to time of operation, surgical times, and complications were recorded. Bilateral hip radiographs at latest follow-up were utilized to record slip angle, alpha angle, greater trochanteric height, and femoral neck length. RESULTS: Thirty-one consecutive hips in 30 patients were reviewed: 15 males (50%) and 15 females (50%), average age 12.37 years (range, 8.75 to 14.8 y), 20 left hips (65%) and 11 right hips (35%). Mean follow-up was 27.9 months (range, 1 to 82 mo). Time from presentation to intervention averaged 13.9 hours (range, 2.17 to 23.4 h). Two patients (6%) developed avascular necrosis at average 19 weeks postoperative. Three patients (10%) developed mild heterotopic ossification requiring no treatment. Two patients (6%) required removal of symptomatic hardware. One patient had hardware failure and in no patients was nonunion, delayed union, or postoperative hip subluxation/dislocation seen. Three patients (10%) presented with bilateral, stable SCFE requiring contralateral in situ pinning. Five patients (16%) had sequential SCFE requiring treatment with 1 patient having an acute, unstable SCFE 10 months after the previous realignment. Mean postoperative slip angle measured 2.5 degrees (range, +19 to -9.4 degrees) (SD, 7.2), alpha angle 47.43 degrees (range, 34 to 64 degrees) (SD, 7.49), greater trochanteric height averaged 3.5 mm below the center of femoral head (-17.5 to +25 mm), and mean femoral neck length difference measured -7.75 mm (range, -1.8 to -18.6 mm). CONCLUSIONS: A single surgeon series of unstable SCFEs treated by a modified Dunn procedure showed a 6% incidence of avascular necrosis and low complication rates at latest follow-up. Radiographs showed restoration of the slip angle, alpha angle, femoral neck length, and greater trochanteric height. This series reveals the safety and effectiveness of the modified Dunn procedure for unstable SCFE. LEVEL OF EVIDENCE: Level III-retrospective review. PMID- 26866641 TI - A New Radiographic Classification System for Developmental Hip Dysplasia is Reliable and Predictive of Successful Closed Reduction and Late Pelvic Osteotomy. AB - BACKGROUND: The Tonnis radiographic classification of developmental dysplasia of the hip (DDH) has been used as a prognostic indicator for patients with walking age DDH. The International Hip Dysplasia Institute (IHDI) classification, a new radiographic classification system, has been proposed to be more reliable by its creators. We sought to validate its reliability using independent observers, to compare it to the Tonnis method, and to assess its prognostic significance in a large cohort of patients. METHODS: A consecutive series of walking-age DDH patients were examined radiographically and classified by the Tonnis and IHDI schemes by 3 independent observers. Interobserver agreement was determined using the Kappa method. Clinical data were collected on patients with regard to success of closed reduction, need for later pelvic osteotomy, and presence of subsequent radiographic avascular necrosis (AVN). The prognostic value of the Tonnis and IHDI classifications to predict these clinical outcomes was determined. RESULTS: A total of 287 hips were available for analysis of the classification schemes. In total, 235 hips underwent attempted closed reduction and were eligible for analysis of successful closed reduction, and 131 hips had >4-year follow-up and were utilized for analysis of late pelvic osteotomy and AVN. Both classifications showed excellent interobserver reliability and in general, there was nonstatistically significant better reliability for the IHDI versus the Tonnis classification. In multivariate analysis, both IHDI and Tonnis classifications were found to be predictive of successful closed reduction and need for late pelvic osteotomy. Both methods showed trends toward being predictive of AVN rate, without statistical significance. CONCLUSIONS: The IHDI classification is subjectively more facile to use and has excellent interrelater agreement for classifying the radiographic severity of DDH. It is also reliable in predicting success of closed reduction and need for late pelvic osteotomy. SIGNIFICANCE: practitioners and researchers should consider the IHDI classification as a useful classification scheme and prognosticator when considering treatment options for late-presenting DDH. SIGNIFICANCE: Practitioners and researchers should consider the IHDI classification as a useful classification scheme and prognosticator when considering treatment options for late-presenting DDH. LEVEL OF EVIDENCE: Level III. PMID- 26866642 TI - Surgical Site Infections following Spine Surgery for Non-idiopathic Scoliosis. AB - BACKGROUND: Surgical site infections (SSIs) following spine surgery in children and adolescents with nonidiopathic scoliosis are associated with increased morbidity and health care costs. Potentially modifiable risk factors for SSIs merit additional study in this population. METHODS: A single-center, retrospective cohort study was performed from August 2008 through December 2013 in children and adolescents undergoing surgery for nonidiopathic scoliosis to determine the trends in SSI rate and causative microorganisms. A standardized perioperative antimicrobial prophylaxis regimen was developed from September October 2008. Potential risk factors for SSIs were assessed by multivariable analysis using Poisson regression models. Fusion procedures and growing construct procedures were analyzed separately. RESULTS: In all, 268 patients underwent 536 surgical procedures of whom 192 underwent 228 fusion procedures, 89 underwent 308 growing construct procedures, and 13 underwent both procedures during the study period. Twenty-one SSIs (3.9% of surgical procedures and 7.8% of patients) occurred within 90 days of surgery, 17 SSIs occurred after fusion procedures (4.5% of procedures and 8.9% of patients), and 4 SSIs occurred after growing construct procedures (1.3% of procedures and 4.5% of patients). There were 9 polymicrobial SSIs (42.9%). Of the 31 bacterial pathogens isolated, 48% were Gram negative organisms. Among patients undergoing fusion procedures, SSIs were associated with underdosing of preoperative cefazolin [relative risk (RR)=4.99; 95% confidence interval (CI), 1.89-17.43; P=0.012] and tobramycin (RR=5.86; 95% CI, 1.90-18.06; P=0.002), underdosing of intraoperative (RR=5.65; 95% CI, 2.13 14.97; P=0.001) and postoperative (RR=3.86; 95% CI, 1.20-12.40; P=0.023) tobramycin, and any preoperative or intraoperative underdosing (RR=4.89; 95% CI, 1.70-14.12; P=0.003), after adjustment for duration of surgery. No factors were associated with SSIs in those undergoing growing construct procedures. During the study period, the SSIs rate declined (P<0.0001). CONCLUSIONS: Underdosing of tobramycin and preoperative cefazolin were associated with an increased SSI risk among patients undergoing fusion procedures. Future multicenter studies should further investigate the generalizability of these findings. LEVEL OF EVIDENCE: Level II-retrospective study. PMID- 26866643 TI - Adolescent Idiopathic Scoliosis Thoracic Volume Modeling: The Effect of Surgical Correction. AB - BACKGROUND: Scoliosis has been shown to have detrimental effects on pulmonary function, traditionally measured by pulmonary function tests, which is theorized to be correlated to the distortion of the spine and thorax. The changes in thoracic volume with surgical correction have not been well quantified. This study seeks to define the effect of surgical correction on thoracic volume in patients with adolescent idiopathic scoliosis. METHODS: Images were obtained from adolescents with idiopathic scoliosis enrolled in a multicenter database (Prospective Pediatric Scoliosis Study). A convenience sample of patients with Lenke type 1 curves with a complete data set meeting specific parameters was used. Blender v2.63a software was used to construct a 3-dimensional (3D) computational model of the spine from 2-dimensional calibrated radiographs. To accomplish this, the 3D thorax model was deformed to match the calibrated radiographs. The thorax volume was then calculated in cubic centimeters using Mimics v15 software. RESULTS: The results using this computational modeling technique demonstrated that surgical correction resulted in decreased curve measurement as determined by Cobb method, and increased postoperative thoracic volume as expected. Thoracic volume significantly increased by a mean of 567 mm (P<0.001). The percent change in thoracic volume after surgical correction averaged 40% (range, 3% to 87%). The smaller the baseline volume, the greater the change in volume postoperatively (r=-0.86).Evaluation of postoperative data demonstrated that spinal curve measurement as determined by Cobb method was significantly reduced from a mean of 69 degrees (range, 50 to 96 degrees) preoperatively to 27 degrees (range, 13 to 33 degrees) postoperatively (P<0.001). CONCLUSIONS: This pilot study demonstrates methodologic plausibility for measuring 3D changes in thoracic volumes using 2-dimensional imaging. This is an assessment of the novel modeling technique, to be used in larger future studies to assess clinical significance. LEVEL OF EVIDENCE: Level 3-retrospective comparison of prospectively collected data. PMID- 26866644 TI - Calcaneofibular Ligament Transfer for Recurrent Peroneal Tendon Subluxation in Pediatric and Young Adult Patients. AB - BACKGROUND: Peroneal tendon subluxation is an uncommon cause of lateral ankle pain and instability but can be disabling for some young patients. Surgical management may be required to restore function for patients who fail nonoperative management. The purpose of this study was to determine the functional outcomes after surgical management of peroneal tendon subluxation in pediatric and adolescent patients. METHODS: A retrospective review of patients presenting to our institution over a 10-year period yielded 18 cases of recurrent subluxation refractory to nonoperative management in 14 children or young adults (mean age 15.0 y). All patients failed nonoperative management and were treated operatively with isolated calcaneofibular ligament transfer to construct a new soft tissue restraint for the peroneal tendons. Patients were evaluated clinically and sent validated questionnaires, including the Foot and Ankle Ability Measure (FAAM) and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale. RESULTS: All 18 ankles of 14 patients had minimum 2-year follow-up. Ten of 18 ankles (55.6%) returned the outcome surveys at an average of 5.7 years after the index procedure (range, 2. 0 to 9.7 y). The average FAAM activities of daily living score was 93.5 (+/-2.9) and the sports subscale was 77.8 (+/-6.1). The mean AOFAS subjective scaled score was 84.3 (+/-4.5). All patients returned to sports and recreational activity. Complications included 1 case of recurrent subluxation (1/18, 5.5%) treated with revision to a Chrisman-Snook procedure and 4 ankles (4/18, 22.2%) with stiffness or arthrofibrosis treated with a secondary procedure of peroneal tendon release or lysis of adhesions. CONCLUSIONS: Surgical management with rerouting of the peroneal tendons under the calcaneofibular ligament appears to be safe and effective for young patients with chronic peroneal tendon subluxation. It provides a low rate of recurrent subluxation, excellent stability, and good long-term functional outcomes. However, the potential for postoperative stiffness appears to be a limitation to the procedure and necessitates aggressive physical therapy to maintain ankle motion. LEVEL OF EVIDENCE: Level IV- retrospective case series. PMID- 26866645 TI - Does a Weekly Didactic Conference Improve Resident Performance on the Pediatric Domain of the Orthopaedic In-Training Examination? AB - BACKGROUND: Performance on the Orthopaedic In-training Examination (OITE) has been correlated with performance on the written portion of the American Board of Orthopaedic Surgery examination. Herein we sought to discover whether adding a regular pediatric didactic lecture improved residents' performance on the OITE's pediatric domain. METHODS: In 2012, a didactic lecture series was started in the University of Pittsburgh Medical Center (UPMC) Hamot Orthopaedic Residency Program (Hamot). This includes all topics in pediatric orthopaedic surgery and has teaching faculty present, and occurs weekly with all residents attending. A neighboring program [UMPC Pittsburgh (Pitt)] shares in these conferences, but only during their pediatric rotation. We sought to determine the effectiveness of the conference by comparing the historic scores from each program on the pediatric domain of the OITE examination to scores after the institution of the conference, and by comparing the 2 programs' scores. RESULTS: Both programs demonstrated improvement in OITE scores. In 2008, the mean examination score was 19.6+/-4.3 (11.0 to 30.0), and the mean percentile was 57.7+/-12.6 (32.0 to 88.0); in 2014, the mean examination score was 23.5+/-4.2 (14.0 to 33.0) and the mean percentile was 67.1+/-12.1 (40.0 to 94.0). OITE scores and percentiles improved with post graduate year (P<0.0001). Compared with the preconference years, Hamot residents answered 3.99 more questions correctly (P<0.0001) and Pitt residents answered 2.93 more questions correctly (P<0.0001). Before the conference, site was not a predictor of OITE score (P=0.06) or percentile (P=0.08); there was no significant difference found between the mean scores per program. However, in the postconference years, site did predict OITE scores. Controlling for year in training, Hamot residents scored higher on the OITE (2.3 points higher, P=0.003) and had higher percentiles (0.07 higher, P=0.004) than Pitt residents during the postconference years. CONCLUSIONS: This study suggests that adding a didactic pediatric lecture improved residents' scores on the OITE and indirectly suggests that more frequent attendance is associated with better scores. LEVEL OF EVIDENCE: Level III-retrospective case-control study. PMID- 26866646 TI - Do Sublaminar Polyester Bands Affect the Outcomes of Postoperative Infections After Adolescent Idiopathic Scoliosis Surgery? AB - BACKGROUND: The incidence of surgical site infections (SSI) after adolescent idiopathic scoliosis (AIS) surgery ranges from 0.5% to 7%. There is currently a regain of interest in hybrid constructs, combining lumbar pedicle screws and thoracic sublaminar bands, but some authors have raised concerns about the risk of SSI and the difficulty of bacterial eradication. The goal of this study was therefore to assess the outcomes of SSI after AIS surgery using sublaminar bands. METHODS: A total of 524 consecutive patients operated for AIS using sublaminar bands between June 2006 and June 2014 were included. SSI cases were identified and analyzed retrospectively. Radiologic and functional outcomes were evaluated at follow-up using EOS imaging and SRS 30 scores, and compared with a control group. RESULTS: The overall SSI rate was 5.3%, with a majority of monomicrobial (86%) infections occurring in the first 6 weeks postoperative (93%). The most frequent pathogens were skin germs (Staphylococcus aureus and Propionibacterium acnes) with a community profile. Patients were treated successfully with surgical debridement without implants removal, associated with 6 weeks of antibiotherapy. However, 25% of patients required >1 surgical debridement. Instrumentation removal was decided in the 2 cases with late SSI, and performed uneventfully. Radiologic and functional outcomes at follow-up were not affected by the occurrence of SSI. CONCLUSIONS: Sublaminar bands are not associated with a higher risk of infection. However, the SSI rate in the current study stands in the upper range of the literature, and other preventive strategies should be considered. In case of early infection, bands removal is not necessary to obtain pathogen eradication, but the sublaminar implants can be pulled out safely in case of late SSI. The occurrence of SSI does not alter the outcomes at follow-up. LEVEL OF EVIDENCE: Level III. PMID- 26866647 TI - Functional Outcome of Humeral Rodding in Children With Osteogenesis Imperfecta. AB - BACKGROUND: The impact of humeral rodding on functional ability in children with osteogenesis imperfecta (OI) has not previously been reported. This article investigates this issue. METHODS: A retrospective chart review was conducted on 35 children with OI who underwent humeral rodding at our institution between 1995 and 2013. Fassier-Duval rods were inserted in 19 cases, K-wires in 13 cases, and Rush rods in 3 cases. Functional ability was assessed preoperatively and every year postoperatively using the self-care and mobility domains of the Pediatric Evaluation of Disability Inventory (PEDI). RESULTS: The mean PEDI self-care score increased by 5.7 (P=0.028) and the mean PEDI mobility score increased by 3.6 (P=0.008) at 1-year postsurgery. Improved function was maintained in the majority of cases at a mean of 7.0 years postcorrection. CONCLUSIONS: Humeral rodding in children with OI leads to significant improvement in functional ability. LEVEL OF EVIDENCE: Level IV. PMID- 26866648 TI - Impairment of the Endothelial Glycocalyx in Cardiogenic Shock and Its Prognostic Relevance: Erratum. AB - The article beginning on page 450 of the May 2015 issue should have contained a note indicating that first authorship was shared: Christian Jung and Georg Fuernau contributed equally to this work. The publisher regrets the omission. PMID- 26866649 TI - The National Mammography Database: Preliminary Data. AB - OBJECTIVE: The purposes of our study were to analyze screening mammography data submitted to the National Mammography Database (NMD) since its inception to confirm data collection feasibility, to draw parallels to data from the Breast Cancer Surveillance Consortium (BCSC), and to examine trends over time. We also retrospectively evaluated practice-level variation in terms of practice type, practice setting, census region, and annual volume. MATERIALS AND METHODS: Data from 90 mammography facilities in the NMD registry were analyzed. The registry receives mammography data collected as part of standard clinical practice, including self-reported demographic information, clinical findings, screening mammography interpretation, and biopsy results. Outcome metrics calculated were cancer detection rate, recall rate, and positive predictive values for biopsy recommended (PPV2) and biopsy performed (PPV3). RESULTS: The NMD successfully collected and analyzed data for 3,181,437 screening mammograms performed between January 2008 and December 2012. Mean values for outcomes were cancer detection rate of 3.43 per 1000 (95% CI, 3.2-3.7), recall rate of 10% (95% CI, 9.3-10.7%), PPV2 of 18.5% (95% CI, 16.7-20.2%), and PPV3 of 29.2% (95% CI, 26.2-32.3%). No statistically significant difference was seen in performance measurements on the basis of practice type, practice setting, census region, or annual volume. NMD performance measurements parallel those reported by the BCSC. CONCLUSION: The NMD has become the fastest growing mammography registry in the United States, providing nationwide performance metrics and permitting comparison with published benchmarks. Our study shows the feasibility of using the NMD to audit mammography facilities and to provide current, ongoing benchmark data. PMID- 26866650 TI - Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice. AB - OBJECTIVE: Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by a mutation in DMD encoding dystrophin. Oxidative stress accounts for dystrophic muscle pathologies in DMD. We examined the effects of molecular hydrogen in mdx mice, a model animal for DMD. METHODS: The pregnant mother started to take supersaturated hydrogen water (>5 ppm) ad libitum from E15.5 up to weaning of the offspring. The mdx mice took supersaturated hydrogen water from weaning until age 10 or 24 weeks when they were sacrificed. RESULTS: Hydrogen water prevented abnormal body mass gain that is commonly observed in mdx mice. Hydrogen improved the spontaneous running distance that was estimated by a counter-equipped running-wheel, and extended the duration on the rota-rod. Plasma creatine kinase activities were decreased by hydrogen at ages 10 and 24 weeks. Hydrogen also decreased the number of central nuclei of muscle fibers at ages 10 and 24 weeks, and immunostaining for nitrotyrosine in gastrocnemius muscle at age 24 weeks. Additionally, hydrogen tended to increase protein expressions of antioxidant glutathione peroxidase 1, as well as anti-apoptotic Bcl-2, in skeletal muscle at age 10 weeks. DISCUSSION: Although molecular mechanisms of the diverse effects of hydrogen remain to be elucidated, hydrogen potentially improves muscular dystrophy in DMD patients. PMID- 26866654 TI - Long-term priming of visual search prevails against the passage of time and counteracting instructions. AB - Studies on intertrial priming have shown that in visual search experiments, the preceding trial automatically affects search performance: facilitating it when the target features repeat and giving rise to switch costs when they change-so called (short-term) intertrial priming. These effects also occur at longer time scales: When 1 of 2 possible target colors is more frequent during an experiment block, this results in a prolonged and persistent facilitation for the color that was biased, long after the frequency bias is gone-so-called long-term priming. In this study, we explore the robustness of such long-term priming. In Experiment 1, participants were fully informed of the bias and instructed to prioritize the other unbiased color. Despite these instructions, long-term priming of the biased color persisted in this block, suggesting that guidance by long-term priming is an implicit effect. In Experiment 2, long-term priming was built up in 1 experimental session and was then assessed in a second session a week later. Long term priming persisted across this week, emphasizing that long-term priming is truly a phenomenon of long-term memory. The results support the view that priming results from the automatic and implicit retrieval of memory traces of past trials. (PsycINFO Database Record PMID- 26866655 TI - A general valence asymmetry in similarity: Good is more alike than bad. AB - The density hypothesis (Unkelbach, Fiedler, Bayer, Stegmuller, & Danner, 2008) claims a general higher similarity of positive information to other positive information compared with the similarity of negative information to other negative information. This similarity asymmetry might explain valence asymmetries on all levels of cognitive processing. The available empirical evidence for this general valence asymmetry in similarity suffers from a lack of direct tests, low representativeness, and possible confounding variables (e.g., differential valence intensity, frequency, familiarity, or concreteness of positive and negative stimuli). To address these problems, Study 1 first validated the spatial arrangement method (SpAM) as a similarity measure. Using SpAM, Studies 2-6 found the proposed valence asymmetry in large, representative samples of self- and other-generated words (Studies 2a/2b), for words of consensual and idiosyncratic valence (Study 3), for words from 1 and many independent information sources (Study 4), for real-life experiences (Study 5), and for large data sets of verbal (i.e., ~14,000 words reported by Warriner, Kuperman, & Brysbaert, 2013) and visual information (i.e., ~1,000 pictures reported in the IAPS; Lang, Bradley, & Cuthbert, 2005; Study 6). Together, these data support a general valence asymmetry in similarity, namely that good is more alike than bad. (PsycINFO Database Record PMID- 26866656 TI - Do we know what we're simulating? Information loss on transferring unconscious perceptual simulation to conscious imagery. AB - Perceptual simulations are unconscious and automatic, whereas perceptual imagery is conscious and deliberate, but it is unclear how easily one can transfer perceptual information from unconscious to conscious awareness. We investigated whether it is possible to be aware of what one is mentally representing; that is, whether it is possible to consciously examine the contents of a perceptual simulation without information being lost. Studies 1 and 2 found that people cannot accurately evaluate the perceptual content of a representation unless attention is explicitly drawn to each modality individually. In particular, when asked to consider sensory experience as a whole, modality-specific auditory, gustatory, and haptic information is neglected, and olfactory and visual information distorted. Moreover, information loss is greatest for perceptually complex, multimodal simulations. Study 3 examined if such information loss leads to behavioral consequences by examining performance during lexical decision, a task whose semantic effects emerge from automatic access to the full potential of unconscious perceptual simulation. Results showed that modality-specific perceptual strength consistently outperformed modality-general sensory experience ratings in predicting latency and accuracy, which confirms that the effects of Studies 1 and 2 are indeed due to information being lost in the transfer to conscious awareness. These findings suggest that people indeed have difficulty in transferring perceptual information from unconscious simulation to conscious imagery. People cannot be aware of the full contents of a perceptual simulation because the act of bringing it to awareness leads to systematic loss of information. (PsycINFO Database Record PMID- 26866658 TI - Searching for the best cause: Roles of mechanism beliefs, autocorrelation, and exploitation. AB - When testing which of multiple causes (e.g., medicines) works best, the testing sequence has important implications for the validity of the final judgment. Trying each cause for a period of time before switching to the other is important if the causes have tolerance, sensitization, delay, or carryover (TSDC) effects. In contrast, if the outcome variable is autocorrelated and gradually fluctuates over time rather than being random across time, it can be useful to quickly alternate between the 2 causes, otherwise the causes could be confounded with a secular trend in the outcome. Five experiments tested whether individuals modify their causal testing strategies based on beliefs about TSDC effects and autocorrelation in the outcome. Participants adaptively tested each cause for longer periods of time before switching when testing causal interventions for which TSDC effects were plausible relative to cases when TSDC effects were not plausible. When the autocorrelation in the baseline trend was manipulated, participants exhibited only a small (if any) tendency toward increasing the amount of alternation; however, they adapted to the autocorrelation by focusing on changes in outcomes rather than raw outcome scores, both when making choices about which cause to test as well as when making the final judgment of which cause worked best. Understanding how people test causal relations in diverse environments is an important first step for being able to predict when individuals will successfully choose effective causes in real-world settings. (PsycINFO Database Record PMID- 26866659 TI - Dissociating appraisals of accuracy and recollection in autobiographical remembering. AB - Recent studies of metamemory appraisals implicated in autobiographical remembering have established distinct roles for judgments of occurrence, recollection, and accuracy for past events. In studies involving everyday remembering, measures of recollection and accuracy correlate highly (>.85). Thus although their measures are structurally distinct, such high correspondence might suggest conceptual redundancy. This article examines whether recollection and accuracy dissociate when studying different types of autobiographical event representations. In Study 1, 278 participants described a believed memory, a nonbelieved memory, and a believed-not-remembered event and rated each on occurrence, recollection, accuracy, and related covariates. In Study 2, 876 individuals described and rated 1 of these events, as well as an event about which they were uncertain about their memory. Confirmatory structural equation modeling indicated that the measurement dissociation between occurrence, recollection and accuracy held across all types of events examined. Relative to believed memories, the relationship between recollection and belief in accuracy was meaningfully lower for the other event types. These findings support the claim that recollection and accuracy arise from distinct underlying mechanisms. (PsycINFO Database Record PMID- 26866657 TI - Prediction in the processing of repair disfluencies: Evidence from the visual world paradigm. AB - Two visual-world eye-tracking experiments investigated the role of prediction in the processing of repair disfluencies (e.g., "The chef reached for some salt uh I mean some ketchup . . ."). Experiment 1 showed that listeners were more likely to fixate a critical distractor item (e.g., pepper) during the processing of repair disfluencies compared with the processing of coordination structures (e.g., ". . . some salt and also some ketchup . . ."). Experiment 2 replicated the findings of Experiment 1 for disfluency versus coordination constructions and also showed that the pattern of fixations to the critical distractor for disfluency constructions was similar to the fixation patterns for sentences employing contrastive focus (e.g., ". . . not some salt but rather some ketchup . . ."). The results suggest that similar mechanisms underlie the processing of repair disfluencies and contrastive focus, with listeners generating sets of entities that stand in semantic contrast to the reparandum in the case of disfluencies or the negated entity in the case of contrastive focus. (PsycINFO Database Record PMID- 26866660 TI - Are you sure the library is that way? Metacognitive monitoring of spatial judgments. AB - Many studies have examined how people recall the locations of objects in spatial layouts. However, little is known about how people monitor the accuracy of judgments based on those memories. The goal of the present experiments was to examine the effect of reference frame characteristics on metacognitive accuracy for spatial judgments. Reference frame characteristics include the alignment of one's viewpoint with the structure of the environment (allocentric alignment), direction of the target with respect to one's current viewpoint (egocentric direction), and the type of perspective used to solve the task (egocentric vs. allocentric). Participants were tested on their knowledge of a well-known location in which they had experience navigating. They were asked to orient themselves toward a particular heading and point to target landmarks from this heading. They then rated their confidence in their pointing judgments. Confidence judgments were sensitive to the effects of allocentric alignment and egocentric direction on performance. However, they underestimate the magnitude of these effects. Follow-up regression analyses indicate that confidence in individual landmarks was a stronger predictor of confidence than reference frame characteristics. Overall, the results suggest that people use reference frame features and landmark confidence when monitoring performance in directional judgments. (PsycINFO Database Record PMID- 26866661 TI - Subnanometer Two-Dimensional Graphene Oxide Channels for Ultrafast Gas Sieving. AB - Two-dimensional (2D) materials with atomic thickness and extraordinary physicochemical properties exhibit unique mass transport behaviors, enabling them as emerging nanobuilding blocks for separation membranes. Engineering 2D materials into membrane with subnanometer apertures for precise molecular sieving remains a great challenge. Here, we report rational-designing external forces to precisely manipulate nanoarchitecture of graphene oxide (GO)-assembled 2D channels with interlayer height of ~0.4 nm for fast transporting and selective sieving gases. The external forces are synergistic to direct the GO nanosheets stacking so as to realize delicate size-tailoring of in-plane slit-like pores and plane-to-plane interlayer-galleries. The 2D channels endow GO membrane with excellent molecular-sieving characteristics that offer 2-3 orders of magnitude higher H2 permeability and 3-fold enhancement in H2/CO2 selectivity compared with commercial membranes. Formation mechanism of 2D channels is proposed on the basis of the driving forces, nanostructures, and transport behaviors. PMID- 26866662 TI - Altered interleukin-18 levels are associated with cognitive impairment in chronic schizophrenia. AB - The pathophysiology of cognitive deficits in schizophrenia may involve the neuroinflammation mediated by cytokines. This study examined the IL-18 levels, the cognitive function, and their association in schizophrenia. We recruited 70 chronic patients and 75 normal controls and examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and IL-18 levels. Positive and Negative Syndrome Scale (PANSS) was assessed in chronic patients. IL-18 levels were increased in chronic patients as compared to normal controls (p < 0.01). RBANS total score and the subscales of immediate memory and delayed memory were lower in patients than controls (all p < 0.001). In patients, IL-18 levels were positively associated with RBANS total score and the subscales of immediate and delayed memory (all p < 0.05). Multiple regression analysis further confirmed that IL-18 was an independent contributor to RBANS total score and the aforementioned two indexes (all p < 0.05). Our data demonstrate that immune responses may play an important role in cognitive deficits in schizophrenia and the abnormal levels of IL-18 reflecting the disturbed balance of proinflammatory and anti-inflammatory mechanisms may be relevant to cognitive deficits of this disorder. PMID- 26866663 TI - Infections in patients with acute myeloid leukemia treated with low-intensity therapeutic regimens: Risk factors and efficacy of antibiotic prophylaxis. AB - Survival of acute myeloid leukemia (AML) patients, who are unfit for high-dose chemotherapy, has significantly improved with the advent of low-intensity therapeutic regimens (LITR, comprising decitabine, azacitidine, and low-dose cytarabine). However, infectious complications are common during LITR treatment and might hamper the beneficial effect of these drugs. In this study, we aimed to evaluate the incidence of and predisposing risk factors for infections during LITR treatment of AML, as well as the value of antibiotic prophylaxis within this setting. Therefore, we retrospectively analyzed 40 AML patients, treated with 215 cycles of LITR and analyzed putative risk factors by multivariate logistic regression. Infections occurred in 53/215 (25%) of LITR cycles, resulting in death in six patients. Of the parameters assessed at the start of each LITR cycle, transfusion dependence (p=0.008) and increased LDH (p=0.027) independently predicted the occurrence of infection. Most importantly, however, antibiotic prophylaxis was independently associated with a decreased rate of infectious complications (p=0.030). It was regularly performed in neutropenic patients and even managed to eliminate low neutrophil counts as risk factor in multivariate models. These data argue for the efficacy of antibiotic prophylaxis during LITR therapy of AML and suggest its further evaluation within a prospective clinical trial. PMID- 26866664 TI - Above and beyond state-of-the-art approaches to investigate sequence data: summary of methods and results from the population-based association group at the Genetic Analysis Workshop 19. AB - This paper summarizes the contributions from the Population-Based Association group at the Genetic Analysis Workshop 19. It provides an overview of the new statistical approaches tried out by group members in order to take best advantage of population-based sequence data.Although contributions were highly heterogeneous regarding the applied quality control criteria and the number of investigated variants, several technical issues were identified, leading to practical recommendations. Preliminary analyses revealed that Hurdle-negative binomial regression is a promising approach to investigate the distribution of allele counts instead of called genotypes from sequence data. Convergence problems, however, limited the use of this approach, creating a technical challenge shared by environment-stratified models used to investigate rare variant-environment interactions, as well as by rare variant haplotype analyses using well-established public software. Estimates of relatedness and population structure strongly depended on the allele frequency of selected variants for inference. Another practical recommendation was that dissenting probability values from standard and small-sample tests of a particular hypothesis may reflect a lack of validity of large-sample approximations. Novel statistical approaches that integrate evolutionary information showed some advantage to detect weak genetic signals, and Bayesian adjustment for confounding was able to efficiently estimate causal genetic effects. Haplotype association methods may constitute a valuable complement of collapsing approaches for sequence data. This paper reports on the experience of members of the Population-Based Association group with several novel, promising approaches to preprocessing and analyzing sequence data, and to following up identified association signals. PMID- 26866665 TI - MCM: one ring to rule them all. AB - Precise replication of the eukaryotic genome is achieved primarily through strict regulation of the enzyme responsible for DNA unwinding, the replicative helicase. The motor of this helicase is a hexameric AAA+ ATPase called MCM. The loading of MCM onto DNA and its subsequent activation and disassembly are each restricted to separate cell cycle phases; this ensures that a functional replisome is only built once at any replication origin. In recent years, biochemical and structural studies have shown that distinct conformational changes in MCM, each requiring post-translational modifications and/or the activity of other replication proteins, define the various stages of the chromosome replication cycle. Here, we review recent progress in this area. PMID- 26866666 TI - Amorphous Red Phosphorus Embedded in Highly Ordered Mesoporous Carbon with Superior Lithium and Sodium Storage Capacity. AB - Red phosphorus (P) have been considered as one of the most promising anode material for both lithium-ion batteries (LIBs) and (NIBs), because of its high theoretical capacity. However, natural insulating property and the large volume expansion of red P during cycling lead to poor cyclability and low rate performance, which prevents its practical application. Here, we significantly improves both lithium storage and sodium storage performance of red P by confining nanosized amorphous red P into the mesoporous carbon matrix (P@CMK-3) using a vaporization-condensation-conversion process. The P@CMK-3 shows a high reversible specific capacity of ~ 2250 mA h g(-1) based on the mass of red P at 0.25 C (~ 971 mA h g(-1) based on the composite), excellent rate performance of 1598 and 624 mA h g(-1) based on the mass of red P at 6.1 and 12 C, respectively (562 and 228 mA h g(-1) based on the mass of the composite at 6.1 and 12 C, respectively) and significantly enhanced cycle life of 1150 mA h g(-1) based on the mass of red P at 5 C (500 mA h g(-1) based on the mass of the composite) after 1000 cycles for LIBs. For Na ions, it also displays a reversible capacity of 1020 mA h g(-1) based on the mass of red P (370 mA h g(-1) based on the mass of the composite) after 210 cycles at 5C. The significantly improved electrochemical performance could be attributed to the unique structure that combines a variety of advantages: easy access of electrolyte to the open channel structure, short transport path of ions through carbon toward the red P, and high ionic and electronic conductivity. PMID- 26866667 TI - KDR gene polymorphisms and idiopathic recurrent spontaneous abortion. AB - OBJECTIVE: Process of angiogenesis is essential for successful gestation. Disruption in this pathway leads to various undesirable consequences in pregnancy such as recurrent spontaneous abortion (RSA). One of the most important genes involved in angiogenesis is kinase-insert domain-containing receptor (KDR). This study aimed to investigate the associations between two single-nucleotide polymorphisms (SNPs) of KDR gene, 1719A > T and 1192G > A, with idiopathic RSA in south-east Iran. METHODS: A total of 230 women, including 110 women with a history of at least two consecutive spontaneous miscarriages and 120 healthy women were recruited in this study. Genomic DNA was extracted from peripheral blood samples of participants using the Salting out method. The KDR 1719A > T and 1192G > A polymorphisms were genotyped by the standard amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. RESULTS: For the case group, frequencies of 2.73%, 30% and 67.27% were observed for AA, AT and TT genotypes in1719A > T SNP, respectively, and the genotype frequencies for controls were equal to AA = 3.33%, AT = 32.5% and TT = 64.17%. Distribution of genotypes in 1192G > A SNP in the case group was 79.1%, 19.1% and 1.8% for GG, AG and AA, respectively, whereas the corresponding values for the controls were GG = 80%, AG = 20% and AA = 0. No significant difference was found between the case and control groups based on the frequency of KDR gene polymorphisms with the susceptibility to RSA. CONCLUSIONS: There is no association between these two SNPs of KDR gene and the susceptibility to RSA in women from south-east Iran. PMID- 26866669 TI - Adsorption of Crystal violet on raw and acid-treated montmorillonite, K10, in aqueous suspension. AB - Crystal violet is used as a dye in cotton and silk textiles, paints and printing ink. The dye is hazardous and exposure to it may cause permanent injury to the cornea and conjunctiva including permanent blindness, and in severe cases, may lead to respiratory and kidney failure. The present work describes removal of Crystal violet from aqueous solution by adsorption on raw and acid-treated montmorillonite, K10. The clay mineral was treated with 0.25 and 0.50 M sulfuric acid and the resulting materials were characterized by XRD, zeta potential, SEM, FTIR, cation exchange capacity, BET surface area and pore volume measurements. The influences of pH, interaction time, adsorbent amount, and temperature on adsorption were monitored and explained on the basis of physico-chemical characteristics of the materials. Basic pH generally favors adsorption but considerable removal was possible even under neutral conditions. Adsorption was very rapid and equilibrium could be attained in 180 min. The kinetics conformed to second order model. Langmuir monolayer adsorption capacity of raw montmorillonite K10 was 370.37 mg g(-1) whereas 0.25 M and 0.50 M acid treated montmorillonite K10 had capacities of 384.62 and 400.0 mg g(-1) respectively at 303 K. Adsorption was exothermic and decreased in the temperature range of 293 323 K. Thermodynamically, the process was spontaneous with Gibbs energy decreasing with rise in temperature. The results suggest that montmorillonite K10 and its acid treated forms would be suitable for removing Crystal violet from aqueous solution. PMID- 26866668 TI - Analysis of Toll-Like Receptor 2 Polymorphism (rs5743704) in Saudi Patients with Primary Open-Angle Glaucoma. AB - AIMS: To investigate whether the single-nucleotide polymorphism (SNP) rs5743704 in the toll-like receptor 2 gene is associated with primary open-angle glaucoma (POAG) or any of its clinical indices in a Saudi cohort. METHOD: Ninety-five unrelated POAG cases and 95 controls of Saudi origin were genotyped utilizing a TaqMan((r)) assay. The association between genotypes and various clinical indices important for POAG were investigated. RESULTS: The genotypic and allelic frequencies among cases were not significantly different when compared to controls. The minor allele frequency was 0.021 in cases and 0.011 in controls. No significant association was seen with intraocular pressure and cup/disc ratio. However, carriers of the C/A genotype had higher number of anti-glaucoma medications compared to controls (p = 0.04). CONCLUSION: SNP rs5773704 is not associated with POAG in a Saudi population. Despite sample size limitation, the association of the minor allele A with higher number of anti-glaucoma medications suggests a possible indirect role for this SNP in predicting disease severity. PMID- 26866670 TI - Evaluation of the influence of methane and copper concentration and methane mass transport on the community structure and biodegradation kinetics of methanotrophic cultures. AB - The environmental conditions during culture enrichment, which ultimately determine its maximum specific biodegradation rate (qmax) and affinity for the target pollutant (Ks), play a key role in the performance of bioreactors devoted to the treatment of methane emissions. This study assessed the influence of Cu(2+) and CH4 concentration and the effective CH4 supply rate during culture enrichment on the structure and biodegradation kinetics of methanotrophic communities. The results obtained demonstrated that an increase in Cu(2+) concentration from 0.05 to 25 MUM increased the qmax and Ks of the communities enriched by a factor of ~ 3, even if the Cu(2+) concentration did not seem to have an effect on the enzymatic "copper switch" and only pMMO was detected. In addition, high Cu(2+) concentrations supported lower diversity coefficients (Hs ~ 1.5* lower) and apparently promoted the growth of more adapted methanotrophs such as Methylomonas. Despite no clear effect of CH4 concentration on the population structure or on the biodegradation kinetics of the communities enriched was recorded at the two low CH4 concentrations studied (1 and 8%), a higher agitation rate increased the qmax by a factor of ~ 2.3 and Ks by a factor of ~ 3.1. PMID- 26866672 TI - Correction to Spatial Variation of Aerosol Chemical Composition and Organic Components Identified by Positive Matrix Factorization in the Barcelona Region. PMID- 26866671 TI - A Case of Juxtaglomerular Cell Tumor, or Reninoma, of the Kidney Treated by Retroperitoneoscopy-Assisted Nephron-Sparing Partial Nephrectomy Through a Small Pararectal Incision. AB - A 15-year-old girl was found to be hypertensive (230-270/140-170 mm Hg) without any subjective symptoms. Magnetic resonance imaging confirmed the presence of a well-defined 22 mm hypodense lesion in the lower pole of the left kidney, located close to the renal hilum. Plasma rennin activity was elevated (75 ng/mL/h), and reninoma was diagnosed. Retroperitoneoscopy-assisted nephron-sparing surgery was planned. The retroperitoneum was accessed through a 4 cm left pararectal upper abdominal incision. Following blunt dissection, the abdominal wall was elevated with a lifting bar and lifting retractor, inserted below the 12th rib in the anterior axillary line to create sufficient working space in the retroperitoneal cavity without the need for pneumoperitoneum. Three 5 mm trocars were introduced above the superior iliac crest for the camera and the assistant. Gerota's fascia was opened and the kidney exposed. The surgeon dissected the left kidney through the minilaparotomy incision under both direct vision and using the magnified view on the monitor, which was particularly effective for the lateral and posterior sides of the kidney. The posterior peritoneum was incised intentionally next to the diaphragm to allow further mobilization of the kidney. Diathermy was used to remove the tumor and a layer of surrounding normal parenchymal tissue at least 0.5 cm thick. The histopathologic diagnosis was reninoma. Ischemia time was 14 minutes. Postoperatively, both plasma rennin activity and blood pressure were normal (1.9 ng/mL/h and 90-110/70-80 mm Hg, respectively). After follow-up of 12 months, there is no evidence of recurrence. PMID- 26866674 TI - Water Use and Management in the Bakken Shale Oil Play in North Dakota. AB - Oil and natural gas development in the Bakken shale play of North Dakota has grown substantially since 2008. This study provides a comprehensive overview and analysis of water quantity and management impacts from this development by (1) estimating water demand for hydraulic fracturing in the Bakken from 2008 to 2012; (2) compiling volume estimates for maintenance water, or brine dilution water; (3) calculating water intensities normalized by the amount of oil produced, or estimated ultimate recovery (EUR); (4) estimating domestic water demand associated with the large oil services population; (5) analyzing the change in wastewater volumes from 2005 to 2012; and (6) examining existing water sources used to meet demand. Water use for hydraulic fracturing in the North Dakota Bakken grew 5-fold from 770 million gallons in 2008 to 4.3 billion gallons in 2012. First-year wastewater volumes grew in parallel, from an annual average of 1,135,000 gallons per well in 2008 to 2,905,000 gallons in 2012, exceeding the mean volume of water used in hydraulic fracturing and surpassing typical 4-year wastewater totals for the Barnett, Denver, and Marcellus basins. Surprisingly, domestic water demand from the temporary oilfield services population in the region may be comparable to the regional water demand from hydraulic fracturing activities. Existing groundwater resources are inadequate to meet the demand for hydraulic fracturing, but there appear to be adequate surface water resources, provided that access is available. PMID- 26866673 TI - Cisplatin in the modern era: The backbone of first-line chemotherapy for non small cell lung cancer. AB - The treatment of advanced non-small cell lung cancer (NSCLC) may be changing, but the cisplatin-based doublet remains the foundation of treatment for the majority of patients with advanced NSCLC. In this respect, changes in practice to various aspects of cisplatin use, such as administration schedules and the choice of methods and frequency of monitoring for toxicities, have contributed to an incremental improvement in patient management and experience. Chemoresistance, however, limits the clinical utility of this drug in patients with advanced NSCLC. Better understanding of the molecular mechanisms of cisplatin resistance, identification of predictive markers and the development of newer, more effective and less toxic platinum agents is required. In addition to maximising potential benefits from advances in molecular biology and associated therapeutics, modification of existing cisplatin-based treatments can still lead to improvements in patient outcomes and experiences. PMID- 26866675 TI - PET Imaging of Carbonic Anhydrase IX Expression of HT-29 Tumor Xenograft Mice with (68)Ga-Labeled Benzenesulfonamides. AB - Carbonic anhydrase IX (CA-IX) is a HIF-1-inducible enzyme that is overexpressed in many cancer subtypes to promote survival and invasion in hypoxic niches. Pharmacologic inhibition of CA-IX is achievable through sulfonamide-based inhibitors and has been shown to reduce primary growth of cancers and distant metastasis in preclinical models. We explored a multivalent approach for targeting CA-IX in vivo, noninvasively, with positron emission tomography. Three (68)Ga-polyaminocarboxylate chelator complex-conjugated tracers containing one, two, or three 4-(2-aminoethyl)benzenesulfonamide moieties were synthesized and evaluated for protein binding and imaging properties. Binding affinity to CA-I, II, -IX, and -XII were determined using a stopped-flow CA catalyzed CO2 hydration assay. Biodistribution and PET/CT imaging were performed using immunocompromised mice bearing CA-IX expressing HT-29 colorectal tumors. Compounds demonstrated good binding affinity to CA-IX (Ki: 7.7-25.4 nM). (68)Ga-labeled sulfonamides were obtained in 64-91% decay-corrected average radiochemical yields with 50-536 GBq/MUmol specific activity and >97% average radiochemical purity. All three tracers allowed for the visualization of tumor xenografts at 1 h postinjection, with the monomer displaying the highest contrast. Tumor uptake of the monomer was blockable in the presence of acetazolamide, confirming target specificity. The monomer was excreted predominantly through the kidneys, while the dimer and trimer were cleared by both renal and hepatobiliary pathways. According to biodistribution analysis, tumor uptake (%ID/g) of the monomeric, dimeric, and trimeric tracers were 0.81 +/- 0.15, 1.93 +/- 0.26, and 2.30 +/- 0.53 at 1 h postinjection. This corresponded to tumor-to-muscle ratios of 5.02 +/- 0.22, 4.07 +/- 0.87, and 4.18 +/- 0.84, respectively. Our data suggest that (68)Ga polyaminocarboxylate chelator-conjugated sulfonamides can be used to noninvasively image CA-IX. These CA-IX targeting PET tracers may be used to identify patients who can benefit from treatments targeting this protein or serve as surrogate imaging agents for tumor hypoxia. PMID- 26866676 TI - Hydroxyphenylation of Histone Lysines: Post-translational Modification by Quinone Imines. AB - Monocyclic aromatic amines are widespread environmental contaminants with multiple sources such as combustion products, pharmaceuticals, and pesticides. Their phenolic metabolites are converted intracellularly to electrophilic quinone imines upon autoxidation and can embed in the cellular matrix through a transimination reaction that leaves a redox-active residue as a substituent of lysine side-chain amino groups. To demonstrate the occurrence of this process within the cellular nucleus, Chinese hamster ovary AA8 cells were treated with the para-phenol of 3,5-dimethylamine, after which the histone proteins were isolated, derivatized, and subjected to tryptic digestion. The resulting peptides were analyzed by tandem mass spectrometry to determine which lysines were modified. Nine residues in histones H2A, H2B, and H4 were identified; these were located in histone tails, close to where DNA makes contact with the nuclear core particle, elsewhere on the protein surface, and deep within the core. Kinetics of disappearance of the modified lysines in cultured cells was determined using isotope-dilution mass spectrometry. AA8 cells were also transfected with the genetically encoded hydrogen peroxide biosensor HyPer in constructs that lead to expression of HyPer in different cellular compartments. Challenging the resulting cells with the dimethylaminophenol resulted in sustained fluorescence emission in each of the compartments, demonstrating ongoing production of H2O2. The kinetics of modified lysine loss determined by mass spectrometry was consistent with persistence of HyPer fluorescence emission. We conclude that the para-phenol of 3,5-dimethylamine can become stably integrated into the histone proteins, which are minimally repaired, if at all, and function as a persistent source of intracellular H2O2. PMID- 26866677 TI - Extinction retention and the menstrual cycle: Different associations for women with posttraumatic stress disorder. AB - The propensity to acquire and retain conditioned fear responses may contribute to the risk of developing and maintaining posttraumatic stress disorder (PTSD) following a traumatic event. There is growing evidence that the gonadal hormones estrogen and progesterone are associated with how well women retain extinction of previously conditioned fear responses. Thus, sex steroid effects may contribute to the increased prevalence of PTSD in women. For the current study, 32 nonmedicated female trauma survivors with and without PTSD completed a differential fear conditioning task both during the early follicular phase of the menstrual cycle when estradiol and progesterone levels are low, and during the midluteal phase when estradiol and progesterone levels are high. Skin conductance served as the measure of conditioned fear. Women with PTSD, compared to those without, showed impaired retention of extinction learning in the midluteal phase of the menstrual cycle. Therefore, the impact of menstrual phase on extinction retention may differ between women with and without PTSD. These findings raise potential considerations regarding the coordination of psychopharmacologic and trauma exposure-based treatments for PTSD with specific phases of the menstrual cycle. PMID- 26866678 TI - A high-performance, flexible and robust metal nanotrough-embedded transparent conducting film for wearable touch screen panels. AB - We report a high-performance, flexible and robust metal nanotrough-embedded transparent conducting hybrid film (metal nanotrough-GFRHybrimer). Using an electro-spun polymer nanofiber web as a template and vacuum-deposited gold as a conductor, a junction resistance-free continuous metal nanotrough network is formed. Subsequently, the metal nanotrough is embedded on the surface of a glass fabric reinforced composite substrate (GFRHybrimer). The monolithic composite structure of our transparent conducting film allows simultaneously high thermal stability (24 h at 250 degrees C in air), a smooth surface topography (Rrms < 1 nm) and excellent opto-electrical properties. A flexible touch screen panel (TSP) is fabricated using the transparent conducting films. The flexible TSP device stably operates on the back of a human hand and on a wristband. PMID- 26866679 TI - Characterization of the size and position of electron-hole puddles at a graphene p-n junction. AB - The effect of an electron-hole puddle on the electrical transport when governed by snake states in a bipolar graphene structure is investigated. Using numerical simulations we show that information on the size and position of the electron hole puddle can be obtained using the dependence of the conductance on magnetic field and electron density of the gated region. The presence of the scatterer disrupts snake state transport which alters the conduction pattern. We obtain a simple analytical formula that connects the position of the electron-hole puddle with features observed in the conductance. The size of the electron-hole puddle is estimated from the magnetic field and gate potential that maximizes the effect of the puddle on the electrical transport. PMID- 26866682 TI - Erratum: Vol. 64, No. 52. PMID- 26866680 TI - Increased asymmetric dimethylarginine levels in severe transient tachypnea of the newborn. AB - OBJECTIVE: Nitric oxide (NO) is synthesized by NO synthase (NOS), and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS. We aimed to investigate l-arginine and ADMA levels in transient tachypnea of the newborn (TTN) and their relationship with systolic pulmonary artery pressure (PAP) and disease severity. STUDY DESIGN: Infants born at ?35 weeks gestational age with clinical signs and chest X-ray findings consistent with TTN were enrolled; controls were recruited at the same time. l-arginine and ADMA levels were measured at 12 to 24 h (first samples) and at 48 to 72 h (second samples). Systolic PAP was evaluated on the second day. Patients were divided according to the duration of tachypnea and designated as group A (duration ?72 h) and group B (duration >72 h). RESULTS: In the first samples, the ADMA levels were significantly higher in patients with TTN compared with controls (P<0.001). In the second samples, the ADMA levels were significantly higher in group B compared with that in group A (P=0.019). In group A patients, the second ADMA levels were significantly lower compared with that in the first samples (P<0.001), whereas the second ADMA levels remained unchanged compared with the first samples in group B. Systolic PAP values were significantly higher in group B compared with that in group A patients (P=0.033). CONCLUSION: Increased ADMA concentration may reduce NO synthesis, leading to increased PAP and thus longer duration of tachypnea. PMID- 26866681 TI - Chest pain: coronary CT in the ER. AB - Cardiac CT has developed into a robust clinical tool during the past 15 years. Of the fields in which the potential of cardiac CT has raised more interest is chest pain in acute settings. In fact, the possibility to exclude with high reliability obstructive coronary artery disease (CAD) in patients at low-to-intermediate risk is of great interest both from the clinical standpoint and from the management standpoint. Several other modalities, with or without imaging, have been used during the past decades in the settings of new onset chest pain or in acute chest pain for both diagnostic and prognostic assessment of CAD. Each one has advantages and disadvantages. Most imaging modalities also focus on inducible ischaemia to guide referral to invasive coronary angiography. The advent of cardiac CT has introduced a new practice diagnostic paradigm, being the most accurate non-invasive method for identification and exclusion of CAD. Furthermore, the detection of subclinical CAD and plaque imaging offer the opportunity to improve risk stratification. Moreover, recent advances of the latest generation CT scanners allow combining both anatomical and functional imaging by stress myocardial perfusion. The role of cardiac CT in acute settings is already important and will become progressively more important in the coming years. PMID- 26866683 TI - Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid. AB - Although the toxicity of melamine to the kidneys and testes is well known, few studies have investigated the effects of melamine on female reproductive organs. Therefore, this study explores the effects of oral administration melamine or melamine and cyanuric acid for 28 days on the ovaries of female rats. Rats that were exposed to the mixture exhibited reduced ovarian and uterine weights, a shorter estrous cycle, and reduced serum estrogen and progesterone levels compared to rats that were exposed to melamine and control rats. Furthermore, morphological analysis revealed pathological changes in the ovaries of rats exposed to melamine or the mixture, such as more atretic follicles and necrosis of oocytes and granulosa cells. TUNEL staining revealed that the exposed groups had a higher proportion of TUNEL-positive granulosa cells than the control group, and the mRNA expressions of SOD1, GPX1, GPX2, P450scc, 17beta-HSD I, and 17beta HSD II were reduced in the exposure groups compared with the control group. These results indicated that exposure to melamine alone or to the melamine-cyanuric acid mixture could damage the ovaries in rats. PMID- 26866686 TI - A Virological Perspective on Cancer. PMID- 26866688 TI - [Not Available]. PMID- 26866684 TI - Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism. AB - BACKGROUND: We examine the clinical significance and biomarkers of tissue plasminogen activator (tPA)-catalyzed clot lysis time (CLT) in patients with intermediate-risk pulmonary embolism (PE). METHODS: Platelet-poor, citrated plasma was obtained from patients with PE. Healthy age- and sex-matched patients served as disease-negative controls. Fibrinogen, alpha2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), plasminogen activator Inhibitor 1 (PAI-1), thrombin time and D-dimer were quantified. Clotting was induced using CaCl2, tissue factor, and phospholipid. Lysis was induced using 60 ng/mL tPA. Time to 50% clot lysis (CLT) was assessed by both thromboelastography (TEG) and turbidimetry (A405). RESULTS: Compared with disease-negative controls, patients with PE exhibited significantly longer mean CLT on TEG (+2,580 seconds, 95% CI 1,380 to 3,720 sec). Patients with PE and a short CLT who were treated with tenecteplase had increased risk of bleeding, whereas those with long CLT had significantly worse exercise tolerance and psychometric testing for quality of life at 3 months. A multivariate stepwise removal regression model selected PAI-1 and TAFI as predictive biomarkers of CLT. CONCLUSION: The CLT from TEG predicted increased risk of bleeding and clinical failure with tenecteplase treatment for intermediate-risk PE. Plasmatic PAI-1 and TAFI were independent predictors of CLT. PMID- 26866685 TI - Factors Associated with Non-Participation and Non-Adherence in Directly Observed Mass Drug Administration for Malaria in The Gambia. AB - INTRODUCTION: The potential benefits of Mass Drug Administration (MDA) for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors that may affect participation and adherence to MDA programs. METHODOLOGY: This social science study was ancillary to a one-round directly observed MDA campaign with dihydroartemisinin-piperaquine, carried out in 12 villages in rural Gambia between June and August 2014. The social science study employed a mixed-methods approach combining qualitative methods (participant observation and in-depth interviewing) and quantitative methods (structured follow-up interviews among non participating and non-adhering community members). RESULTS: Of 3942 people registered in the study villages, 67.9% adhered to the three consecutive daily doses. For the remaining villagers, 12.6% did not attend the screening, 3.5% was not eligible and 16% did not adhere to the treatment schedule. The main barriers for non-participation and adherence were long and short-term mobility of individuals and specific subgroups, perceived adverse drug reactions and rumors, inconveniences related to the logistics of MDA (e.g. waiting times) and the perceived lack of information about MDA. CONCLUSION: While, there was no fundamental resistance from the target communities, adherence was 67.9%. This shows the necessity of understanding local perceptions and barriers to increase its effectiveness. Moreover, certain of the constraining factors were socio spatially clustered which might prove problematic since focal areas of residual malaria transmission may remain allowing malaria to spread to adjacent areas where transmission had been temporarily interrupted. PMID- 26866687 TI - Using the Web to Collect Data on Sensitive Behaviours: A Study Looking at Mode Effects on the British National Survey of Sexual Attitudes and Lifestyles. AB - BACKGROUND: Interviewer-administered surveys are an important method of collecting population-level epidemiological data, but suffer from declining response rates and increasing costs. Web surveys offer more rapid data collection and lower costs. There are concerns, however, about data quality from web surveys. Previous research has largely focused on selection biases, and few have explored measurement differences. This paper aims to assess the extent to which mode affects the responses given by the same respondents at two points in time, providing information on potential measurement error if web surveys are used in the future. METHODS: 527 participants from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3), which uses computer assisted personal interview (CAPI) and self-interview (CASI) modes, subsequently responded to identically-worded questions in a web survey. McNemar tests assessed whether within-person differences in responses were at random or indicated a mode effect, i.e. higher reporting of more sensitive responses in one mode. An analysis of pooled responses by generalized estimating equations addressed the impact of gender and question type on change. RESULTS: Only 10% of responses changed between surveys. However mode effects were found for about a third of variables, with higher reporting of sensitive responses more commonly found on the web compared with Natsal-3. CONCLUSIONS: The web appears a promising mode for surveys of sensitive behaviours, most likely as part of a mixed-mode design. Our findings suggest that mode effects may vary by question type and content, and by the particular mix of modes used. Mixed-mode surveys need careful development to understand mode effects and how to account for them. PMID- 26866689 TI - [Treatment of Chronic Functional Constipation during Pregnancy and Lactation]. AB - Natural fibres (bulk-forming agents), docusate sodium (stool-softener), mineral oils (lubricant laxatives), macrogol (polyethylene glycol, PEG), sugars and sugar alcohols (osmotic laxatives) and anthraquinones and diphenolic laxatives (stimulant laxatives) seem to be safe medicaments regarding teratogenicity and lactation. The US Food and Drug Administration (FDA) risk categories for these substances taken during pregnancy and lactation are often the result of the lack of studies than of evidence-based information. So risk categories do not help in the decision-making for the right laxative. Alternative solutions such as proposals of the American College of Gastroenterology's Committee on FDA related matters, (ACG-FDA) and the Motherisk Programme try to improve decision-making. For newer compounds such as chloride-channel-activators and procinetics no data regarding safe use in pregnancy and during breast-feeding are available as yet. We suggest the use of macrogol and lactulose as the first-line therapy in treating chronic constipation during pregnancy. Macrogol shows some advantages, such as faster onset of bowel action and fewer flatulences. If this treatment does not work or starts but then stops working, we recommend in the second and third trimenon a second-line treatment with diphenolic laxatives such as bisacodyl and and sodium picosulfate. During pregnancy the decision on the application of these laxatives is largely determined by the side-effects of tenesmus associated with preterm births. During lactation we recommend macrogol (preferable to lactulose due to the lack of data), lactulose, bisacodyl and sodium picosulfate, according to the nature of the conditions. PMID- 26866690 TI - [Anxiety of Pregnant Women with Prior Miscarriage Before and After Prenatal Diagnosis]. AB - PURPOSE: Aim of the investigation is to assess the anxiety in pregnant women with prior miscarriage and without prior miscarriage before and after prenatal testing for congenital anomalies. MATERIAL AND METHODS: Are sampling is carried of 50 pregnant women with prior miscarriage and 224 pregnant women without prior miscarriage between the 11th and 22th week of gestation who are presenting themselves for the first time for specific prenatal diagnostics. I study state and trait anxiety levels (Spielberger) before and state anxiety after prenatal diagnosis. Data processing and evaluation were carried out with the SPSS Version 18.0. RESULTS: Prior to the prenatal examination, women with prior miscarriage report more state anxiety symptoms then women without miscarriage (t-test, p value 0.035), but not more trait anxiety (t-test, p-value 0.794). After prenatal examination no differ in state anxiety scale between pregnant women with prior miscarriage and pregnant women without prior miscarriage (t-test, p-value 0.909). CONCLUSION: The study suggests that miscarriages may lead to higher levels of state anxiety before prenatal diagnosis. Gynaecologists and prenatal experts should be pay attention and response the fear actively during prenatal examination and after prenatal examination. Anxiety may have negative consequences for obstetric outcomes, parenting and infant behaviours. PMID- 26866691 TI - [Staphylococcal Scalded Skin Syndrome in a Very Low Birth Weight Premature Infant]. AB - INTRODUCTION: Staphylococcal scalded skin syndrome (SSSS) was often endemic in the past but is nowadays rare. The hematogeneous spread of exfoliative toxins A (ETA) or B (ETB) produced by specific Staphylococcus aureus strains causes a scald-like eruption with disseminated bullous lesions. CASE REPORT: A perioral impetigo lesion occurred on day 14 of life in a preterm male infant (1,065 g, 30 weeks of gestational age). Empiric antibiotic therapy with cefotaxime and vancomycin was given for 6 days and led to complete resolution. A Staphylococcus aureus strain was isolated. After a symptom-free interval a relapse was noted on day 26 of life. Despite restarting the antibiotic therapy immediately the initial lesion expanded, and disseminated flaccid blisters on an erythematous base appeared within a few hours. On histological examination the cleavage was in the level of the granular layer. There was no mucosal involvement, and the Nikolsky I sign was positive. The antibiotic therapy was changed to a combination of cefotaxime, flucloxacillin and clindamycin which rapidly stopped progression of the exfoliation. Supportive therapy included adequate analgesia, parenteral rehydration, and application of local antiseptics. The preterm infant completely recovered. In the primary lesion an ETA-producing Staphylococcus aureus strain was isolated. Nasal microtrauma by a nasogastric tube was assumed to have caused the fulminant disease. At the same time, no other Staphylococcus aureus infections were seen in our Department of Neonatology. DISCUSSION: According to the literature, the incidence of SSSS is higher in premature infants and newborns than in older children. Possible causes include lower antibody levels against exfoliative toxins and renal immaturity. Rapid diagnosis and immediate appropriate antibiotic therapy are essential to prevent secondary infection, dehydration with electrolyte disturbance, death, and endemic spread. PMID- 26866693 TI - Synergistic Combination of Electrolysis and Electroporation for Tissue Ablation. AB - Electrolysis, electrochemotherapy with reversible electroporation, nanosecond pulsed electric fields and irreversible electroporation are valuable non-thermal electricity based tissue ablation technologies. This paper reports results from the first large animal study of a new non-thermal tissue ablation technology that employs "Synergistic electrolysis and electroporation" (SEE). The goal of this pre-clinical study is to expand on earlier studies with small animals and use the pig liver to establish SEE treatment parameters of clinical utility. We examined two SEE methods. One of the methods employs multiple electrochemotherapy-type reversible electroporation magnitude pulses, designed in such a way that the charge delivered during the electroporation pulses generates the electrolytic products. The second SEE method combines the delivery of a small number of electrochemotherapy magnitude electroporation pulses with a low voltage electrolysis generating DC current in three different ways. We show that both methods can produce lesion with dimensions of clinical utility, without the need to inject drugs as in electrochemotherapy, faster than with conventional electrolysis and with lower electric fields than irreversible electroporation and nanosecond pulsed ablation. PMID- 26866692 TI - Using an Insect Mushroom Body Circuit to Encode Route Memory in Complex Natural Environments. AB - Ants, like many other animals, use visual memory to follow extended routes through complex environments, but it is unknown how their small brains implement this capability. The mushroom body neuropils have been identified as a crucial memory circuit in the insect brain, but their function has mostly been explored for simple olfactory association tasks. We show that a spiking neural model of this circuit originally developed to describe fruitfly (Drosophila melanogaster) olfactory association, can also account for the ability of desert ants (Cataglyphis velox) to rapidly learn visual routes through complex natural environments. We further demonstrate that abstracting the key computational principles of this circuit, which include one-shot learning of sparse codes, enables the theoretical storage capacity of the ant mushroom body to be estimated at hundreds of independent images. PMID- 26866694 TI - Two Independent Functions of Collier/Early B Cell Factor in the Control of Drosophila Blood Cell Homeostasis. AB - Blood cell production in the Drosophila hematopoietic organ, the lymph gland, is controlled by intrinsic factors and extrinsic signals. Initial analysis of Collier/Early B Cell Factor function in the lymph gland revealed the role of the Posterior Signaling Center (PSC) in mounting a dedicated cellular immune response to wasp parasitism. Further, premature blood cell differentiation when PSC specification or signaling was impaired, led to assigning the PSC a role equivalent to the vertebrate hematopoietic niche. We report here that Collier is expressed in a core population of lymph gland progenitors and cell autonomously maintains this population. The PSC contributes to lymph gland homeostasis by regulating blood cell differentiation, rather than by maintaining core progenitors. In addition to PSC signaling, switching off Collier expression in progenitors is required for efficient immune response to parasitism. Our data show that two independent sites of Collier/Early B Cell Factor expression, hematopoietic progenitors and the PSC, achieve control of hematopoiesis. PMID- 26866695 TI - Characterization of Regulatory T-Cell Markers in CD4+ T Cells of the Upper Airway Mucosa. AB - CD4+ T regulatory cells (Tregs) comprise a heterogeneous population of cells the regulate immune responses and prevent autoimmunity. Most reports on human Tregs are derived from studies of peripheral blood, although Tregs mainly exert their functions in the periphery. Here we performed a detailed analysis of Tregs in the human upper airway mucosa under non-inflammatory conditions, and found that 10% of all CD4+ T cells expressed the transcription factor FOXP3 and the memory marker CD45RO, as well as high levels of CTLA-4. The majority of FOXP3+CD4+ T cells co-expressed the transcription factor Helios and produced very little cytokines, compatible with being thymus-derived Tregs. FOXP3+Helios-CD4+ T cells were more heterogeneous. A mean of 24% produced the immunomodulatory cytokine IL 10, whereas a large fraction also produced IL-2, IFN-MU or IL-17. A significant population (6%) of FOXP3-negative T cells also produced IL-10, usually in combination with IFN-MU. Together, we found that CD4+ T cells in the upper airways differed functionally from their counterparts in peripheral blood, including higher expression of IL-10. Moreover, our findings suggest that several subsets of CD4+ T cells with functionally distinct regulatory properties reside in the upper airway mucosa which should be taken into account when targeting Tregs for therapy. PMID- 26866696 TI - Trends in Malaria in Odisha, India-An Analysis of the 2003-2013 Time-Series Data from the National Vector Borne Disease Control Program. AB - BACKGROUND: Although Odisha is the largest contributor to the malaria burden in India, no systematic study has examined its malaria trends. Hence, the spatio temporal trends in malaria in Odisha were assessed against the backdrop of the various anti-malaria strategies implemented in the state. METHODS: Using the district-wise malaria incidence and blood examination data (2003-2013) from the National Vector Borne Disease Control Program, blood examination-adjusted time trends in malaria incidence were estimated and predicted for 2003-2013 and 2014 2016, respectively. An interrupted time series analysis using segmented regression was conducted to compare the disease trends between the pre (2003 2007) and post-intensification (2009-2013) periods. Key-informant interviews of state stakeholders were used to collect the information on the various anti malaria strategies adopted in the state. RESULTS: The state annual malaria incidence declined from 10.82/1000 to 5.28/1000 during 2003-2013 (adjusted annual decline: -0.54/1000, 95% CI: -0.78 to -0.30). However, the annual blood examination rate remained almost unchanged from 11.25% to 11.77%. The keyinformants revealed that intensification of anti-malaria activities in 2008 led to a more rapid decline in malaria incidence during 2009-2013 as compared to that in 2003-2007 [adjusted decline: -0.83 (-1.30 to -0.37) and -0.27 (-0.41 to 0.13), respectively]. There was a significant difference in the two temporal slopes, i.e., -0.054 (-0.10 to -0.002, p = 0.04) per 1000 population per month, between these two periods, indicating almost a 200% greater decline in the post intensification period. Although, the seven southern high-burden districts registered the highest decline, they continued to remain in that zone, thereby, making the achievement of malaria elimination (incidence <1/1000) unlikely by 2017. CONCLUSION: The anti-malaria strategies in Odisha, especially their intensification since 2008, have helped improve its malaria situation in recent years. These successful measures need to be sustained and perhaps intensified further for eliminating malaria from Odisha. PMID- 26866697 TI - Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs). AB - Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although pi-pi stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self exfoliation and antibacterial property against both Gram-positive and Gram negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits. PMID- 26866699 TI - Leprosy Diagnostic Test Development As a Prerequisite Towards Elimination: Requirements from the User's Perspective. PMID- 26866701 TI - Phase transformation controlled tetragonality of MnNi-based nanocrystals. AB - The phase transformation controlled tetragonality of MnNi nanostructures has attracted wide interest for their shape memory effect. In this study, MnNi nanocrystals were selected to epitaxially grow an FeCo shell, where the antiferromagnetic L1(0) phase transformation of the MnNi core triggers the tetragonal distortion in the magnetically soft FeCo shell. The tetragonality change of L1(0) MnNi under thermal annealing enables the control of the tetragonality of the FeCo phase, ultimately increasing magnetocrystalline anisotropy and coercivity. This study opens up a new route to fabricate functional nanostructures with unique magnetic properties. PMID- 26866698 TI - A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model. AB - Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development. PMID- 26866702 TI - CLINICAL AND COST-EFFECTIVENESS OF INSULIN DELIVERY WITH V-GO((r)) DISPOSABLE INSULIN DELIVERY DEVICE VERSUS MULTIPLE DAILY INJECTIONS IN PATIENTS WITH TYPE 2 DIABETES INADEQUATELY CONTROLLED ON BASAL INSULIN. AB - OBJECTIVE: To compare two methods of delivering intensified insulin therapy (IIT) in patients with type 2 diabetes inadequately controlled on basal insulin +/- concomitant antihyperglycemic agents in a real-world clinical setting. METHODS: Data for this retrospective study were obtained using electronic medical records from a large multicenter diabetes system. Records were queried to identify patients transitioned to V-Go((r)) disposable insulin delivery device (V-Go) or multiple daily injections (MDI) using an insulin pen to add prandial insulin when A1C was >7% on basal insulin therapy. The primary endpoint was the difference in A1C change using follow-up A1C results. RESULTS: A total of 116 patients were evaluated (56 V-Go, 60 MDI). Both groups experienced significant glycemic improvement from similar mean baselines. By 27 weeks, A1C least squares mean change from baseline was -1.98% (-21.6 mmol/mol) with V-Go and -1.34% (-14.6 mmol/mol) with MDI, for a treatment difference of -0.64% (-7.0 mmol/mol; P = .020). Patients using V-Go administered less mean +/- SD insulin compared to patients using MDI, 56 +/- 17 units/day versus 78 +/- 40 units/day (P<.001), respectively. Diabetes-related direct pharmacy costs were lower with V-Go, and the cost inferential from baseline per 1% reduction in A1C was significantly less with V-Go ($118.84 +/- $158.55 per patient/month compared to $217.16 +/- $251.66 per patient/month with MDI; P = .013). CONCLUSION: Progression to IIT resulted in significant glycemic improvement. Insulin delivery with V-Go was associated with a greater reduction in A1C, required less insulin, and proved more cost-effective than administering IIT with MDI. ABBREVIATIONS: A1C = glycated hemoglobin ANCOVA = analysis of covariance CI = confidence interval CSII = continuous subcutaneous insulin infusion FPG = fasting plasma glucose IIT = intensified insulin therapy LSM = least squares mean MDI = multiple daily injections T2DM = type 2 diabetes mellitus TDD = total daily dose. PMID- 26866700 TI - Family-based approaches: design, imputation, analysis, and beyond. AB - Participants in the family-based analysis group at Genetic Analysis Workshop 19 addressed diverse topics, all of which used the family data. Topics addressed included questions of study design and data quality control (QC), genotype imputation to augment available sequence data, and linkage and/or association analyses. Results show that pedigree-based tests that are sensitive to genotype error may be useful for QC. Imputation quality improved with inclusion of small amounts of pedigree information used to phase the data in evaluation of 5 commonly used approaches for imputation in samples of (typically) unrelated subjects. It improved still further when pedigree-based imputation using larger pedigrees was also added. An important distinction was made between methods that do versus do not make use of Mendelian transmission in pedigrees, because this serves as a key difference between underlying models and assumptions. Methods that model relatedness generally had higher power in association testing than did analyses that carry out testing in the presence of a transmission model, but this may reflect details of implementation and/or ability of more general methods to jointly include data from larger pedigrees. In either case, for single nucleotide polymorphism-set approaches, weights that incorporate information on functional effects may be more useful than those that are based only on allele frequencies. The overall results demonstrate that family data continue to provide important information in the search for trait loci. PMID- 26866704 TI - TACKLING A BIG PROBLEM WITH LITTLE EVIDENCE: IMPROVING RESEARCH INTO POSTTRANSPLANTATION DIABETES. PMID- 26866705 TI - TRABECULAR BONE SCORE IN PATIENTS WITH NORMOCALCEMIC HYPERPARATHYROIDISM. AB - OBJECTIVE: The effects of normocalcemic hyperparathyroidism (NHPT) on bone remain unclear. The objective of this study was to evaluate differences in the trabecular bone score (TBS) of NHPT patients and asymptomatic hypercalcemic hyperparathyroidism (HHPT) patients. METHODS: We performed a prospective study that enrolled consecutive patients with asymptomatic hyperparathyroidism (NHPT and HHPT) with a follow-up >=1 year at the University Hospital of Valladolid, Spain. Metabolic phosphocalcium plasma and urine parameters were evaluated in >=2 determinations during follow-up to classify patients as NHPT patients or asymptomatic HHPT patients. A control group was enrolled during the same period. TBS and bone mineral density (BMD) were evaluated. RESULTS: Thirty-nine patients with asymptomatic HPT (24 with NHPT and 15 with HHPT) and 24 controls were recruited. NHPT patients and HHPT patients had a similar mean age, vitamin D level, TBS, and areal BMD (all sites). Compared to controls, symptomatic HPT patients had significantly higher parathyroid hormone (PTH) and calcium levels and significantly lower TBS and areal BMD at all sites (all P<.05). A significant negative relationship between TBS and PTH was found in asymptomatic HPT patients (r = -0.320, P = .043), which remained significant after adjustment for age, sex, and body mass index. CONCLUSION: There was no difference in the TBS between NHPT and HHPT patients. However, there was a reduction in the TBS of patients with asymptomatic HPT that was related to PTH levels but had no repercussion on bone mass. Higher levels of PTH seem to be responsible for this alteration in microarchitecture texture. ABBREVIATIONS: aBMD = areal bone mineral density BMD = bone mineral density BMI = body mass index DXA = dual-energy X-ray absorptiometry HHPT = hypercalcemic hyperparathyroidism HPT = hyperparathyroidism HR-MRI = high resolution magnetic resonance HR-pQcT = high-resolution peripheral quantitative computed tomography NHPT = normocalcemic hyper-parathyroidism PTH = parathyroid hormone TBS = trabecular bone score 25vitD = 25-hydroxyvitamin D. PMID- 26866706 TI - THE ROLE OF GLUCAGON IN THE PATHOPHYSIOLOGY AND MANAGEMENT OF DIABETES. AB - OBJECTIVE: There is general recognition that insulin and glucagon are the main hormones involved in the pathophysiology of diabetes, but the role of glucagon in diabetes is complex and in some circumstances controversial. The increasing appreciation of the role of glucagon in currently used hypoglycemic agents and the ongoing development of glucagon-targeted therapies underscores glucagon's important contribution in optimizing diabetes management. The current review provides a background on glucagon physiology and pathophysiology and an update for investigators, endocrinologists, and other healthcare providers on glucagon modulating therapies. METHODS: A literature review was conducted utilizing published literature in PubMed and AccessMedicine including the years 1922-2015 using the following key words: glucagon, bihormonal, diabetes mellitus, glucagon antagonists, glucagon-targeted therapies. RESULTS: Glucagon is a counterregulatory hormone that promotes hepatic glucose production, thus preventing hypoglycemia in normal physiology. In patients with diabetes mellitus, glucagon secretion may be unregulated, which contributes to problems with glucose homeostasis. Several of the most effective therapies for diabetes have been found to suppress glucagon secretion or action, which may contribute to their success. Additionally, glucagon-specific targeted therapies, such as glucagon receptor antagonists, are being studied at a basic and clinical level. CONCLUSION: Glucagon plays an important role in contributing to hyperglycemia in patients with diabetes. Utilizing hypoglycemic agents that decrease glucagon secretion or inhibit glucagon action can help improve glycemic control, making these agents a valuable resource in diabetes therapy. PMID- 26866707 TI - THE IMPACT OF AGE IN THE MANAGEMENT OF HYPOTHYROIDISM: RESULTS OF A NATIONWIDE SURVEY. AB - OBJECTIVE: Evidence exists that thyroid-stimulating hormone (TSH) increases with age and lowering the TSH goal in older patients on thyroid hormone may cause over treatment. Risks of overtreatment include cardiac and skeletal events. We assessed practice patterns regarding TSH goals and explored factors influencing physicians' decision making when managing hypothyroidism. METHODS: Members of the American College of Physicians, the American Academy of Family Practice, and the Endocrine Society were surveyed to determine goal TSH when treating hypothyroidism. RESULTS: Fifty-three percent of physicians reported factoring patient age into their decision making when managing hypothyroidism. Patient age was prioritized third (53%), following patient symptoms (69.2%) and cardiac arrhythmias (65.7%). In multivariable analysis, endocrinologists (P = .002), internists (P = .049), physicians in academic settings (P = .003), and high volume physicians (P = .021) were more likely to consider patient age when determining goal TSH. When presented with scenarios differing in patient gender and age, 90% of physicians targeted a TSH <=3.0 mIU/L in 30-year-old patients. Fifty-three percent of respondents targeted a TSH <=3.0 mIU/L in octogenarians, but 90% targeted a TSH >1.5 mIU/L in this group. Regardless of gender, physician reported TSH goal ranges (0.1 to 0.5, 0.6 to 1.5, 1.6 to 3.0, and 3.1 to 5.0 mIU/L) increased in a direct relationship to patient age (P<.001). CONCLUSION: Just over half of physicians consider patient age when determining TSH goal. When presented with scenarios differing in patient age and gender, physicians targeted a higher TSH goal in octogenarians. This may indicate an attempt to avoid overtreatment in this group. Consensus is needed among physicians regarding the role of patient age in hypothyroidism management. ABBREVIATIONS: TSH = thyroid stimulating hormone. PMID- 26866708 TI - AXIAL BMD IN DIABETIC AND NONDIABETIC SOUTHEAST ASIANS WITH HIP FRACTURES: DO RACE AND BODY MASS INDEX MATTER? AB - OBJECTIVE: Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI. METHODS: We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures. RESULTS: The presence of T2DM was associated with higher BMD (g/cm(2)) at the femoral neck (0.527 +/- 0.103 vs. 0.491 +/- 0.102, P<.01) and lumbar spine [LS] (0.798 +/- 0.147 vs. 0.723 +/- 0.156, P<.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI <18.5 kg/m(2)) diabetics compared to similar weight nondiabetics (0.733 +/- 0.126 vs. 0.649 +/- 0.131 g/cm(2), P = .014). CONCLUSION: T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI. ABBREVIATIONS: BMD = bone mineral density BMI = body mass index CV = coefficient of variation DXA = dual-energy X-ray absorptiometry HbA1c = glycated hemoglobin IGF-1 = insulin growth factor-1 LS = lumbar spine 25(OH)D = 25 hydroxyvitamin D T2DM = type 2 diabetes mellitus. PMID- 26866709 TI - Emerging roles of lncRNAs in senescence. AB - Cellular senescence is a complex stress response that leads to an irreversible state of cell growth arrest. Senescence may be induced by various stimuli such as telomere shortening, DNA damage or oncogenic insult, among others. Senescent cells are metabolically highly active, producing a wealth of cytokines and chemokines that, depending on the context, may have a beneficial or deleterious effect on the organism. Senescence is considered a tightly regulated stress response that is largely governed by the p53/p21 and p16/Rb pathways. Many molecules have been identified as regulators of these two networks, such as transcription factors, chromatin modifiers and non-coding RNAs. The expression level of several long non-coding RNAs is affected during different types of senescence; however, which of these are important for the biological function remains poorly understood. Here we review our current knowledge of the mechanistic roles of lncRNAs affecting the main senescence pathways, and discuss the importance of identifying new regulators. PMID- 26866710 TI - The Use of Low-Dose Oral Glucocorticoids Was Minimized in the 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis: Comment on the Article by Singh et al. PMID- 26866712 TI - Alu retroelement-associated autoimmunity in Sjogren's syndrome. PMID- 26866714 TI - DNA-Based Sensor Particles Enable Measuring Light Intensity in Single Cells. AB - "Lab on a particle" architecture is employed in designing a light nanosensor. Light-sensitive protecting groups are installed on DNA, which is encapsulated in silica particles, qualifying as a self-sufficient light sensor. The nanosensors allow measuring light intensity and duration in very small volumes, such as single cells, and store the irradiation information until readout. PMID- 26866713 TI - Antagonistic Effects of Insulin and TGF-beta3 during Chondrogenic Differentiation of Human BMSCs under a Minimal Amount of Factors. AB - Growth factors are crucial regulators of cell differentiation towards tissue and organ development. Insulin and transforming growth factor-beta (TGF-beta) have been used as the major factors for chondrogenesis in vitro, by activating the AKT and Smad signaling pathways. Previous reports demonstrated that AKT and Smad3 have a direct interaction that results in the inhibition of TGF-beta-mediated cellular responses. However, the result of this interaction between AKT and Smad3 during the chondrogenesis of human bone marrow-derived stem/progenitor cells (hBMSCs) is unknown. In this study, we performed functional analyses by inducing hBMSCs into chondrogenesis with insulin, TGF-beta3 or in combination, and found that TGF-beta3, when applied concomitantly with insulin, significantly decreases an insulin-induced increase in mRNA levels of the master regulator of chondrogenesis, SOX9, as well as the regulators of the 2 major chondrocyte markers, ACAN and COL2A1. Similarly, the insulin/TGF-beta3-treated group presented a significant decrease in the deposition of cartilage matrix as detected by safranin O staining of histological sections of hBMSC micromass cultures when compared to the group stimulated with insulin alone. Intracellular analysis revealed that insulin-induced activation of AKT suppressed Smad3 activation in a dose-dependent manner. Accordingly, insulin/TGF-beta3 significantly decreased the TGF-beta3-induced increase in mRNA levels of the direct downstream factor of TGF-beta/Smad3, CCN2/CGTF, compared to the group stimulated with TGF-beta3 alone. On the other hand, insulin/TGF-beta3 stimulation did not suppress insulin-induced expression of the downstream targets TSC2 and DDIT4/REDD1. In summary, insulin and TGF-beta3 have antagonistic effects when applied concomitantly, with a minimal number of factors. The application of an insulin/TGF-beta3 combination without further supplementation should be used with caution in the chondrogenic differentiation of hBMSCs. PMID- 26866711 TI - Continuous End-Tidal Carbon Dioxide Monitoring during Resuscitation of Asphyxiated Term Lambs. AB - BACKGROUND: The Neonatal Resuscitation Program (NRP) recommends close monitoring of oxygenation during the resuscitation of newborns using a pulse oximeter. However, there are no guidelines for monitoring carbon dioxide (CO2) to assess ventilation. Considering that cerebral blood flow (CBF) correlates directly with PaCO2, continuous capnography monitoring of end-tidal CO2 (ETCO2) may limit fluctuations in PaCO2 and, therefore, CBF during resuscitation of asphyxiated infants. OBJECTIVE: To evaluate whether continuous monitoring of ETCO2 with capnography during resuscitation of asphyxiated term lambs with meconium aspiration will prevent fluctuations in PaCO2 and carotid arterial blood flow (CABF). METHODS: Fifty-four asphyxiated term lambs with meconium aspiration syndrome were mechanically ventilated from birth to 60 min of age. Ventilatory parameters were adjusted based on clinical observation (chest excursion) and frequent arterial blood gas analysis in 24 lambs (control group) and 30 lambs (capnography group) received additional continuous ETCO2 monitoring. Left CABF was monitored. We aimed to maintain PaCO2 between 35 and 50 mm Hg and ETCO2 between 30 and 45 mm Hg. RESULTS: There was a significant correlation between ETCO2 and PaCO2 (R = 0.7, p < 0.001), between PaCO2 and carotid flow (R = 0.52, p < 0.001) and between ETCO2 and carotid flow (R = 0.5, p < 0.001). PaCO2 and CABF during the first 60 min of age showed significantly higher fluctuation in the control group compared to the capnography group. CONCLUSION: Continuous monitoring of ETCO2 using capnography with mechanical ventilation during and after resuscitation in asphyxiated term lambs with meconium aspiration limits fluctuations in PaCO2 and CABF and may potentially limit brain injury. PMID- 26866715 TI - HLA-DPB1 as a Risk Factor for Relapse in Antineutrophil Cytoplasmic Antibody Associated Vasculitis: A Cohort Study. AB - OBJECTIVE: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) form a group of small-vessel vasculitides with systemic involvement. Although the etiology of AAVs remains largely unknown, both genetic and environmental factors have been implicated. Recently, certain alleles in the HLA DPB1 region on chromosome 6 were shown to be associated with proteinase 3 (PR3) ANCA-positive AAV but not with myeloperoxidase (MPO)-ANCA-positive AAV. The aim of this study was to investigate whether different alleles in the HLA-DPB1 region have clinical and/or prognostic implications in AAV. METHODS: One hundred seventy four patients with a diagnosis of AAV were recruited at the Maastricht University Medical Centre between 2000 and 2009. Seventeen different HLA-DPB1 alleles were determined using the restriction fragment length polymorphism technique. A validation cohort of 170 AAV patients from the Vasculitis Centre of Luebeck/Bad Bramstedt was included. RESULTS: In the initial cohort, the distribution of HLA DPB1 alleles was significantly different between PR3-ANCA-positive compared with MPO-ANCA-positive AAV patients, ANCA-negative AAV patients, and healthy controls. Importantly, HLA-DPB1*04:01 was present in 90% of PR3-ANCA-positive AAV patients compared with 63% of MPO-ANCA-positive AAV patients, 58% of ANCA-negative patients, and 63% of healthy controls. Patients homozygous for HLA-DPB1*04:01 had relapses more often compared with heterozygous patients and noncarrier patients. This association persisted after correction for ANCA subtype and diagnosis. In the validation cohort, patients homozygous for HLA-DPB1*04:01 and those heterozygous for HLA-DPB1*04:01 had relapses more often compared with noncarrier patients. When both patient cohorts were merged (n = 344), homozygous patients relapsed most often, followed by heterozygous patients and noncarrier patients. CONCLUSION: Carriage of HLA-DPB1*04:01 in patients with AAV is significantly associated with an increased risk of relapse compared with HLA-DPB1*04:01 negative patients, irrespective of ANCA status or clinical AAV entity. PMID- 26866716 TI - Microphase Separation within Disk Shaped Aggregates of Triblock Bottlebrushes. AB - Well-defined AbBA triblock bottlebrush with poly(N,N-dimethyl acrylamide) (PAm) as A block and polyacrylate, densely grafted with poly(tert-butyl acrylate)-block polystyrene (PBA-b-PS), as brush bB block is prepared by controlled radical polymerization and click chemistry. The triblock copolymer with a composition of PAm200 -b-b(PBA14 -b-PS47 )167 -b-PAm200 is obtained and is further transformed into PAm200 -b-b(PAA14 -b-PS47 )167 -b-PAm200 by hydrolysis of the PBA segment into poly(acrylic acid) (PAA). In a mixture of N,N-dimethylformamide (DMF) and methanol, a poor solvent of bB block, PAm200 -b-b(PAA14 -b-PS47 )167 -b-PAm200 self-assembled into disk-like platelets, which have an internal lamellar structure by further microphase-separation of PAA-b-PS branches in 2D. Moreover, Ag nanoparticles are aligned by PAA segments along the disk to form a pattern. PMID- 26866717 TI - Tranexamic acid for preventing postpartum blood loss at cesarean delivery: is evidence sufficient? PMID- 26866718 TI - Management of patients with Graves' orbitopathy: initial assessment, management outside specialized centres and referral pathways. PMID- 26866719 TI - Association of Serum Uric Acid and Disease Duration With Frequent Gout Attacks: A Case-Control Study. AB - OBJECTIVE: To ascertain whether readily available disease and demographic factors associate with frequent acute attacks of gout, and to find out whether they can identify patients especially at risk of recurrent gout attacks. METHODS: Data from 3 previous studies at Academic Rheumatology, University of Nottingham, UK, were used. Patients taking urate lowering treatment (ULT) were excluded, as it influences gout flare frequency. Logistic regression was used to examine the association between age, sex, body mass index (BMI), disease duration, cardiovascular comorbidities, tophi, serum uric acid (SUA), and >2 acute attacks of gout in the previous 12 months. Receiver operating curves were plotted to examine their ability in identifying patients with recurrent gout attacks. RESULTS: A total of 468 gout patients (88.5% men, mean +/- SD age 62.2 +/- 11.3 years, BMI 29.8 +/- 5.0 kg/m(2) ) were included. Disease duration and SUA associated independently with >2 acute attacks of gout in the previous 12 months (adjusted odds ratio 1.36 [95% confidence interval (95% CI) 1.08-1.72] and 1.27 [95% CI 1.10-1.46], respectively). However, these factors performed poorly in identifying patients with frequent gout attacks, with an area under the curve (AUC) of 0.61, and there was an insignificant increase in AUC on adding other variables (AUC 0.64). CONCLUSION: Higher SUA and longer disease duration associate independently with frequent gout attacks, presumably because of greater crystal load. This association supports early consideration of ULT for gout patients with higher SUA. However, as readily available disease and demographic factors perform poorly in identifying patients with frequent gout attacks, further research is required to ascertain the reasons underlying interpersonal variations in frequency of gout attacks. PMID- 26866721 TI - Correction: CoPt/CeO2 catalysts for the growth of narrow diameter semiconducting single-walled carbon nanotubes. AB - Correction for 'CoPt/CeO2 catalysts for the growth of narrow diameter semiconducting single-walled carbon nanotubes' by Lei Tang et al., Nanoscale, 2015, DOI: 10.1039/c5nr05616k. PMID- 26866720 TI - Effect of weak permanent magnetic field on lipid composition and content in perilla leaves. AB - Composition and content of lipids were studied in leaves of red perilla plants (Perilla nankinensis [Lour.] Decne.) grown in weak permanent horizontal magnetic field (PMF) of 500 uT flux density under controlled illumination, temperature, and humidity in the phytothron chamber. Control plants were grown under similar conditions, but without PMF exposure. Exposure of perilla plants for a month to PMF retarded plant flowering as compared to control. PMF treatment increased total lipid content, including polar lipids, among them glycolipids and phospholipids. PMF did not affect content of neutral lipids. It is concluded that PMF stimulated synthesis of membrane lipids of chloroplasts, mitochondria, and cytoplasm in perilla leaves. A possible role of PMF as a factor imitating the additional light source retarding flowering of a short-day perilla plants is discussed. PMID- 26866722 TI - Tatton-Brown-Rahman syndrome due to 2p23 microdeletion. AB - Tatton-Brown-Rahman syndrome is a new overgrowth syndrome due to DNMT3A (DNA cytosine 5 methyltransferase 3A) mutations. Mutation carriers show a distinctive facial appearance, intellectual disability, and increased height. We report a patient with overgrowth who showed submicroscopic deletion of chromosome 2p23 including DNMT3A. The deletion was detected by array-CGH. He showed moderate ID and distinctive facial gestalt. His clinical features were consistent with those of Tatton-Brown-Rahman syndrome. We suggest that 2p23 microdeletion including DNMT3A may cause similar symptoms in patients with DNMT3A mutations and should be considered in patients with overgrowth. PMID- 26866723 TI - Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3 Dioxygenase Activity and an Imbalanced Kynurenine Pathway in Interferon-Positive Primary Sjogren's Syndrome. AB - OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan to kynurenine, is driven in part by type I and type II interferons (IFNs). Naive T cells are polarized into FoxP3+ Treg cells upon exposure to either IDO+ cells or kynurenine. Recent studies have suggested that the kynurenine pathway reflects a crucial interface between the immune and nervous system. The aims of the present study were to evaluate whether Treg cell levels are elevated, in conjunction with increased IDO activity, in patients with primary Sjogren's syndrome (SS) who are positive for the IFN gene expression signature, and to investigate the downstream kynurenine pathway in these patients. METHODS: Serum from 71 healthy controls, 58 IFN-negative patients with primary SS, and 66 IFN-positive patients with primary SS was analyzed using high performance liquid chromatography to measure the levels of tryptophan and kynurenine. Expression levels of messenger RNA (mRNA) for IDO and downstream enzymes in the kynurenine pathway were assessed in CD14+ monocytes using real time quantitative polymerase chain reaction. CD4+CD45RO+ T helper memory cell populations were analyzed by flow cytometry. RESULTS: Significantly increased levels of IDO activity (assessed as the kynurenine:tryptophan ratio) (P = 0.0054) and percentages of CD25(high) FoxP3+ Treg cells (P = 0.039) were observed in the serum from IFN-positive patients with primary SS, and these parameters were significantly correlated with one another (r = 0.511, P = 0.002). In circulating monocytes from IFN-positive patients with primary SS, the expression of IDO1 mRNA was up-regulated (P < 0.0001), and this was correlated with the IFN gene expression score (r = 0.816, P < 0.0001). Interestingly, the proapoptotic and neurotoxic downstream enzyme kynurenine 3-monooxygenase was up-regulated (P = 0.0057), whereas kynurenine aminotransferase I (KATI) (P = 0.0003), KATIII (P = 0.016), and KATIV (P = 0.04) were down-regulated in IFN-positive patients with primary SS compared to healthy controls. CONCLUSION: These findings demonstrate enhanced IDO activity in conjunction with increased percentages of CD25(high) FoxP3+ Treg cells in primary SS patients who carry the IFN signature. In addition, IFN-positive patients with primary SS exhibit an imbalanced kynurenine pathway, with evidence of a shift toward potentially more proapoptotic and neurotoxic metabolites. Intervening in these IFN- and IDO-induced immune system imbalances may offer a new array of possibilities for therapeutic interventions in patients with primary SS. PMID- 26866725 TI - beta-Globin-Expressing Definitive Erythroid Progenitor Cells Generated from Embryonic and Induced Pluripotent Stem Cell-Derived Sacs. AB - Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent a potential alternative source for red blood cell transfusion. However, when using traditional methods with embryoid bodies, ES cell-derived erythroid cells predominantly express embryonic type E-globin, with lesser fetal type gamma globin and very little adult type beta-globin. Furthermore, no beta-globin expression is detected in iPS cell-derived erythroid cells. ES cell-derived sacs (ES sacs) have been recently used to generate functional platelets. Due to its unique structure, we hypothesized that ES sacs serve as hemangioblast-like progenitors capable to generate definitive erythroid cells that express beta globin. With our ES sac-derived erythroid differentiation protocol, we obtained ~120 erythroid cells per single ES cell. Both primitive (E-globin expressing) and definitive (gamma- and beta-globin expressing) erythroid cells were generated from not only ES cells but also iPS cells. Primitive erythropoiesis is gradually switched to definitive erythropoiesis during prolonged ES sac maturation, concurrent with the emergence of hematopoietic progenitor cells. Primitive and definitive erythroid progenitor cells were selected on the basis of glycophorin A or CD34 expression from cells within the ES sacs before erythroid differentiation. This selection and differentiation strategy represents an important step toward the development of in vitro erythroid cell production systems from pluripotent stem cells. Further optimization to improve expansion should be required for clinical application. Stem Cells 2016;34:1541-1552. PMID- 26866727 TI - "Are you looking at me?" How children's gaze judgments improve with age. AB - Adults' judgments of another person's gaze reflect both sensory (e.g., perceptual) and nonsensory (e.g., decisional) processes. We examined how children's performance on a gaze categorization task develops over time by varying uncertainty in the stimulus presented to 6- to 11- year-olds (n = 57). We found that younger children responded "direct" over a wider range of gaze deviations. We also found that increasing uncertainty led to an increase in direct responses, across all age groups. A simple model to account for these data revealed that although younger children had a noisier sensory representation of the stimulus, most developmental changes in gaze were because of a change in children's response criteria (category boundaries). These results suggest that although the core mechanisms for gaze processing are already in place by the age of 6, their development continues across the whole of childhood. (PsycINFO Database Record PMID- 26866726 TI - Girls' and boys' problem talk: Implications for emotional closeness in friendships. AB - This research highlights the critical role of gender in the context of problem talk and social support in adolescents' friendships. Early- and middle adolescents' (N = 314 friend dyads; Ms = 13.01 and 16.03 years) conversations about problems were studied using observation and a short-term longitudinal design. Mean-level gender differences emerged in that girls participated in problem talk more than boys and responded in a more positive and engaged manner to friends' statements about problems (e.g., by saying something supportive, asking a question) than did boys. Interestingly, boys used humor during problem talk more than girls. Despite mean-level differences, there were not gender differences in the functional significance of participating in problem talk and positive engaged responses in that these behaviors predicted increased friendship closeness for both boys and girls. In contrast, humor during problem talk predicted increased closeness only for boys, highlighting an understudied pathway to closeness in boys' friendships. PMID- 26866728 TI - The development of visual search in infancy: Attention to faces versus salience. AB - Four experiments examined how faces compete with physically salient stimuli for the control of attention in 4-, 6-, and 8-month-old infants (N = 117 total). Three computational models were used to quantify physical salience. We presented infants with visual search arrays containing a face and familiar object(s), such as shoes and flowers. Six- and 8-month-old infants looked first and longest at faces; their looking was not strongly influenced by physical salience. In contrast, 4-month-old infants showed a visual preference for the face only when the arrays contained 2 items and the competitor was relatively low in salience. When the arrays contained many items or the only competitor was relatively high in salience, 4-month-old infants' looks were more often directed at the most salient item. Thus, over ages of 4 to 8 months, physical salience has a decreasing influence and faces have an increasing influence on where and how long infants look. PMID- 26866729 TI - Influenza-Related Hospitalizations and Poverty Levels - United States, 2010-2012. AB - Annual influenza vaccine is recommended for all persons aged >=6 months in the United States, with recognition that some persons are at risk for more severe disease (1). However, there might be previously unrecognized demographic groups that also experience higher rates of serious influenza-related disease that could benefit from enhanced vaccination efforts. Socioeconomic status (SES) measures that are area-based can be used to define demographic groups when individual SES data are not available (2). Previous surveillance data analyses in limited geographic areas indicated that influenza-related hospitalization incidence was higher for persons residing in census tracts that included a higher percentage of persons living below the federal poverty level (3-5). To determine whether this association occurs elsewhere, influenza hospitalization data collected in 14 FluSurv-NET sites covering 27 million persons during the 2010-11 and 2011-12 influenza seasons were analyzed. The age-adjusted incidence of influenza-related hospitalizations per 100,000 person-years in high poverty (>=20% of persons living below the federal poverty level) census tracts was 21.5 (95% confidence interval [CI]: 20.7-22.4), nearly twice the incidence in low poverty (<5% of persons living below the federal poverty level) census tracts (10.9, 95% CI: 10.3 11.4). This relationship was observed in each surveillance site, among children and adults, and across racial/ethnic groups. These findings suggest that persons living in poorer census tracts should be targeted for enhanced influenza vaccination outreach and clinicians serving these persons should be made aware of current recommendations for use of antiviral agents to treat influenza (6). PMID- 26866730 TI - Exosomes promote bone marrow angiogenesis in hematologic neoplasia: the role of hypoxia. AB - PURPOSE OF REVIEW: To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions. RECENT FINDINGS: Cross-talk between bone marrow tumor cells and surrounding cells, including endothelial cells, is important for tumor growth in hematologic neoplasia. In addition to conventional signaling pathways, exosomes, which are small endosome-derived vesicles containing miRNAs, can help to modulate the microenvironment without directly contacting nontumorous cells. The human myeloid leukemia cell line K562 secretes exosomes containing a large amount of miR-92a that enhances angiogenesis under normoxic and hypoxic conditions. With chronic hypoxia, exosomes secreted by multiple myeloma cells also enhance angiogenesis by targeting factor-inhibiting hypoxia-inducible factor 1 via miR-135b. SUMMARY: Intercellular communication between tumor cells and a heterogeneous population of bone marrow stromal cells is mediated by exosomes containing various functional proteins, mRNA, and miRNA. Hypoxia is a major regulator of exosomal content and affects angiogenesis in various types of hematologic neoplasia. Functional analysis of exosomes and exosome-mediated cell cell interactions not only clarifies molecular pathogenesis but also suggests new treatment strategies for hematologic neoplasia through targeting exosomes. PMID- 26866731 TI - Teaching Handoff Communication to Nursing Students: A Teaching Intervention and Lessons Learned. AB - When new-graduate nurses enter practice, they are expected to provide clear, effective handoff reports during care transitions. However, few nursing programs offer systematic instruction or opportunities to practice this important form of communication. This article describes a teaching intervention designed to prepare students with handoff skills they will need in practice. Data gathered to evaluate its effectiveness indicated that skill repetition improved student performance and perceived self-efficacy of handoff reporting. Lessons learned and recommendations for incorporating this instruction into nursing curricula are discussed. PMID- 26866732 TI - Supports and Barriers to Successful Progression in a DNP Program: Students' and Graduates' Perspectives. AB - This study examined the supports, barriers, and strategies to successful progression in a DNP program using a nationwide online survey of DNP students and graduates. Subjects (n = 172) had a mean age of 46.2 years; 83% worked full time. Major barriers were competing demands of work, family, and school. Perseverance was a key element in overcoming barriers; most students reported being overwhelmed, and 37% considered quitting. Mechanisms for programs to consider in addressing this stress are discussed. PMID- 26866733 TI - Impact of Attendance on Academic Performance in Prenursing Students. AB - A descriptive-correlational design was used to explore the relationship between attendance and course grade in a prenursing course. Findings revealed that attendance was positively associated with final course grades (r443 = 0.54, P < .001). Traditional students attended a significantly higher percentage of classes than their nontraditional counterparts. These findings support the long-held belief by nursing faculty that attendance positively impacts course outcomes. PMID- 26866735 TI - Interventions to increase the use of electronic health information by healthcare practitioners to improve clinical practice and patient outcomes. PMID- 26866734 TI - Influence of Nursing Faculty Discussion Presence on Student Learning and Satisfaction in Online Courses. AB - This study determined the relationships between faculty participation in online discussions with student satisfaction and perceived learning in online RN-BSN and MSN courses. Analysis of faculty participation in online courses (n = 280) demonstrated a relationship between faculty participation and student satisfaction and perceived learning. The results of this study offer guidance on the minimal faculty participation necessary in online discussions in nursing courses. PMID- 26866736 TI - Neurologic Outcomes of Complex Adult Spinal Deformity Surgery: Results of the Prospective, Multicenter Scoli-RISK-1 Study. AB - STUDY DESIGN: Prospective, multicenter, international observational study. OBJECTIVE: To evaluate motor neurologic outcomes in patients undergoing surgery for complex adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: The neurologic outcomes after surgical correction for ASD have been reported with significant variability and have not been measured as a primary endpoint in any prospective, multicenter, observational study. METHODS: The primary outcome measure was the change in American Spinal Injury Association (ASIA) Lower Extremity Motor Scores (LEMS) obtained preoperatively, and at hospital discharge, 6 weeks and 6 months postoperatively. RESULTS: A total of 273 patients with complex ASD underwent surgery at 15 sites worldwide. One patient was excluded for lack of preoperative LEMS. The remaining 272 patients were divided into two groups: normal preoperative LEMS (=50) (Preop NML, N = 204, 75%) and abnormal preoperative LEMS (<50) (Preop ABNML, N = 68, 25%). At hospital discharge, 22.18% of patients showed a decline in LEMS compared with 12.78% who showed an improvement. At 6 weeks, there was a significant change compared with discharge: 17.91% patients showed a decline in LEMS and 16.42% showed an improvement. At 6 months, 10.82% patients showed a decline in preoperative LEMS, 20.52% improvement, and 68.66% maintenance. This was a significant change compared with 6 weeks and at discharge. CONCLUSION: Although complex ASD surgery can restore neurologic function in patients with a preoperative neurologic deficit, a significant portion of patients with ASD experienced postoperative decline in LEMS. Measures that can anticipate and reduce the risk of postoperative neurologic complications are warranted. LEVEL OF EVIDENCE: 3. PMID- 26866737 TI - Case-Matched Comparison of Spinal Fusion Versus Growing Rods for Progressive Idiopathic Scoliosis in Skeletally Immature Patients. AB - STUDY DESIGN: Multicenter study of retrospectively and prospectively collected data. OBJECTIVES: To compare outcomes of spinal fusion (SF) versus growing rod (GR) surgery using a case-matched series. SUMMARY OF BACKGROUND DATA: Scoliosis surgeons face two distinct treatment options for progressive idiopathic scoliosis in skeletally immature patients: definitive SF or growth-friendly surgery such as GR. No previous studies have directly compared outcomes between these two techniques. METHODS: A multicenter database identified 11 GR patients who met the following criteria: (1) idiopathic etiology; (2) 9 years to 11 years old at initial surgery; (3) major thoracic curve; (4) had "final" SF. A second multicenter database was used to identify SF patient matches. A one-to-one patient match was performed based on age, major curve size, and curve apex. RESULTS: Preoperative age was 10.1 years for GR and 10.8 years for SF (P = 0.003). GR had a mean 2.8 lengthenings before final fusion. Follow-up time after spinal fusion (3.8 vs. 4.5 years; P = 0.51) and age at latest follow-up (16.4 vs. 15.3 years; P = 0.28) were similar between GR and SF groups. Initial curve correction was significantly greater for SF compared with GR after initial GR surgery (71% vs. 38%; P < 0.001). SF patients had better overall curve correction at latest follow-up (63% vs. 44%; P = 0.08). Overall increase in T1-S1 was 23% for GR and 19% for SF (P = 0.42). Overall increase in T1-T12 was 19% for GR and 17% for SF (P = 0.76). Complications requiring unplanned surgery occurred in one GR patient and two SF patients. Number of surgeries was significantly higher in GR (54) compared with SF (13). CONCLUSION: SF patients had greater curve correction and marginally less spinal and thoracic height gain compared with GR patients. GR patients underwent significantly more surgical procedures. These findings suggest GR treatment does not benefit older patients with juvenile idiopathic scoliosis. LEVEL OF EVIDENCE: 4. PMID- 26866738 TI - Repeated 3.0 Tesla Magnetic Resonance Imaging After Clinically Successful Lumbar Disc Surgery. AB - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To describe the naturally occurring magnetic resonance imaging (MRI) findings after successful microsurgical removal of lumbar disc herniation with repeated MRI examinations. SUMMARY OF BACKGROUND DATA: The interpretation of MRI after spinal surgery may be particularly challenging and image findings do not always correlate to clinical findings. Early postoperative MRI has limited value in the evaluation of patients after surgery for lumbar disc herniation. METHODS: Prospective study of 30 successfully operated patients, which underwent 3.0 T MRI within 24 h after surgery for lumbar disc herniation and repeated at 6 weeks and 3 months postoperatively. Postoperative image findings (nerve root enhancement, nerve root thickening, displacement or compression of the nerve root, and residual mass size and signal) were assessed quantitatively. Inter-rater reliability was tested. RESULTS: Inter-rater reliability between neuroradiologists was moderate for assessed MRI variables. In the immediate postoperative phase, compression or dislocation of the nerve root at the operated level was common. A residual mass at the operated level was seen in 80%, 47%, and 33% after 24 h, 6 weeks, and 3 months, respectively. Postoperative dislocation or compression of the nerve root from residual masses was seen in 67%, 24%, and 14% after 24 h, 6 weeks, and 3 months, respectively. A residual mass with a higher signal than muscle on T2 weighted images was seen in 80%, 30%, and 17% after 24 h, 6 weeks, and 3 months, respectively. CONCLUSION: A residual mass with compression or dislocation of the nerve root at the operated level, that disappears over 3 months, is a common MRI finding in patients successfully operated for symptomatic lumbar disc herniation. An expectant approach instead of early reoperations may perhaps be preferred in patients with residual pain and root compression due to residual masses with high T2-signal since these often seem to resolve spontaneously. LEVEL OF EVIDENCE: 3. PMID- 26866739 TI - Prevalence of Idiopathic Scoliosis in Chinese Schoolchildren: A Large, Population Based Study. AB - STUDY DESIGN: This is a population-based, cross-sectional study of school scoliosis screening program in mainland China. OBJECTIVE: The aim of this study was to assess current prevalence and distribution of idiopathic scoliosis (IS) in schoolchildren and to compare with the results of previous studies. SUMMARY OF BACKGROUND DATA: The feasibility and predictive values of scoliosis screening programs for school-age children remains controversial and many of these programs have recently been discontinued in different countries. Due to different race and medical model in China, it is not feasible to introduce these data without further study. Therefore, a reliable retrospective cohort study with a large sample size to ensure proper evaluation of school scoliosis screening is needed. METHODS: Schoolchildren were initially screened by visual inspection of clinical signs, the forward-bending test, and the measurement of the angle of trunk rotation (ATR). Students suspected were rescreened, and then were referred for radiography or dismissed. The diagnosis and treatment were based on the Cobb angle. The personal information, demographic information, and results of tests performed were recorded and analyzed. RESULTS: A total of 99,695 children were screened, with a female-to-male ratio of 1:1.03. Around 6.56% of children screened were referred for radiography, and 5125 of them had confirmed diagnosis. The overall scoliosis prevalence rate was 5.14%. According to age and gender, 14- to 15-year-old girls had the highest prevalence rates (13.81%). And, the prevalence of IS in need of treatment was 0.64%. A prevalence rate of 13.1% was observed in girls with BMI less than 18 kg/m2. CONCLUSION: The prevalence rate of IS was 5.14% in our study. Screening of 13- to 14- and 14- to 15-year-old girls identified a significant number who could benefit from preventive treatment. Low BMI may be a risk factor for IS. We present this study as a guide for studying the prevalence of IS and modifying our further research. LEVEL OF EVIDENCE: 3. PMID- 26866740 TI - The Impact of Advanced Age on Peri-Operative Outcomes in the Surgical Treatment of Cervical Spondylotic Myelopathy: A Nationwide Study Between 2001 and 2010. AB - STUDY DESIGN: Retrospective multicenter database review. OBJECTIVE: The aim of this study was to evaluate national postoperative outcomes and hospital characteristics trends from 2001 to 2010 for advanced age CSM patients. SUMMARY OF BACKGROUND DATA: Recent studies show increases in US cervical spine surgeries and CSM diagnoses. However, few have compared national outcomes for elderly and younger CSM patients. METHODS: A Nationwide Inpatient Sample (NIS) analysis from 2001 to 2010, including CSM patients 25+ who underwent anterior and/or posterior cervical fusion or laminoplasty. Fractures, 9+ levels fused, or any cancers were excluded. Measures included demographics, outcomes, and hospital-related data for 25 to 64 versus 65+ and 65 to 75 versus 76+ age groups. Univariate and logistic regression modeling evaluated procedure-related complications risk in 65+ and 76+ age groups (OR[95% CI]). RESULTS: Discharges for 35,319 patients in the age range of 25 to 64 years and 19,097 at the age 65+ years were identified. Average comorbidity indices for patients at 65+ years were higher compared to the 25 to 64 years age group (0.79 vs. 0.0.44, P < 0.0001), as was the total complications rate (11.39% vs. 5.93%, P < 0.0001) and charges ($57,449.94 vs. $49,951.11, P < 0.0001). Hospital course for aged 65+ patients was longer (4.76 vs. 3.26 days, P < 0.0001). Mortality risk was higher in the 65+ cohort (3.38[2.93-3.91]), adjusted for covariates. 65+ patients had increased risk of all complications except device-related, for which they had decreased risk (0.61[0.56-0.67]). Patients 76+ years displayed increased hospital charges ($59,197.60 vs. $56,601.44, P < 0.001) and courses (5.77 vs. 4.28 days, P < 0.001) compared to those in the age group 65 to 75 years. These same patients presented with increased Deyo scores (0.83 vs. 0.77, P < 0.001), had increased total complications rate (13.87% vs. 10.20%, P < 0.001), and displayed increased risk for postoperative shock (6.34 [11.16-3.60], P < 0.001), digestive system (1.92 [2.40-1.54], P < 0.001), and wound dehiscence (1.71 [2.56-1.15], P < 0.001). CONCLUSION: Patients aged 65+ years undergoing CSM surgical management have a higher mortality risk, more procedure-related complications, higher comorbidity burden, longer hospital course, and higher charges. This study provides clinically useful data for surgeons to educate patients and to improve outcomes. PMID- 26866741 TI - Patient-Based Surgical Outcomes of Posterior Lumbar Interbody Fusion: Patient Satisfaction Analysis. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The purpose of this study was to investigate: (1) patient-based surgical outcomes of posterior lumbar interbody fusion (PLIF); (2) correlations between patient-based surgical outcomes and surgeon-based surgical outcomes; (3) factors associated with patient satisfaction. SUMMARY OF BACKGROUND DATA: There have been no reports of patient based surgical outcomes of PLIF for lumbar spondylolisthesis. METHODS: Patients who underwent PLIF for L4 degenerative spondylolisthesis between 2006 and 2009 were reviewed (n = 121). Surgical outcomes were assessed 5 years after primary surgery using a questionnaire, a numerical rating scale (NRS) of pain, the 36 Item Short Form Health Survey (SF-36), the Japanese Orthopedic Association score (JOA score), and the recovery rate. The original questionnaire consisted of 5 categories, with scoring out of 100 points for surgery, satisfaction, improvement, recommendation to others, and willingness to undergo repeat surgery. Patient-based outcomes were divided into 3 groups according to the questionnaire responses as positive, intermediate, and negative and were compared with the JOA scores. RESULTS: A total of 103 patients responded, for a response rate of 85%. The average patient-evaluated score for surgery was 82 points. The positive response rate in each category was 78% for satisfaction, 88% for improvement, 74% for recommendation, and 71% for repeat. The average pre- and postoperative JOA scores were 11.2 and 23.2, respectively. The average recovery rate was 68.5%. There were significant correlations between patient-based surgical outcomes and the JOA score. Furthermore, there were significant correlations between patient based surgical outcomes and the NRS and physical component scores of the SF-36. Postoperative permanent motor loss was a major factor related to a negative response. CONCLUSION: The patient-evaluated score for surgery was 82 points. More than 70% of patients gave positive responses in all sections of the questionnaire. There were significant correlations between patient-based and surgeon-based surgical outcomes. LEVEL OF EVIDENCE: 2. PMID- 26866742 TI - Predictive Value of Six Prognostic Scoring Systems for Spinal Bone Metastases: An Analysis Based on 1379 Patients. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to assess and compare the predictive accuracy of six models designed to estimate survival of patients suffering from spinal bone metastases Just (SBMs). SUMMARY OF BACKGROUND DATA: On the basis of the estimated survival of patients with SBM, extent of treatment can be adjusted. To aid clinicians in the difficult task of assessing probability of survival, prognostic scoring systems have been developed by Tomita, Tokuhashi, Van der Linden, Bauer, Rades, and Bollen. METHODS: All patients who were treated for SBM between 2000 and 2010 were included in this international, multicenter, retrospective study (n = 1379). Medical records were reviewed for all items needed to use the scoring systems. Survival time was calculated as the difference between start of treatment for SBM and date of death. Survival curves were estimated using the Kaplan-Meier method and accuracy was assessed with the c-statistic. Survival rates of the worst prognostic groups were evaluated at 4 months. RESULTS: Median follow-up was 6.7 years [95% confidence interval (95% CI) 5.6-7.7] with a minimum of 2.3 years and a maximum of 12.3 years. The overall median survival was 5.1 months (95% CI 4.6-5.6). The most common primary tumors were breast (n = 388, 28%), lung (n = 318, 23%), and prostate cancer (n = 259, 19%). The Tokuhashi, Bauer, Tomita, and Van der Linden models performed similar with a c-statistic of 0.64 to 0.66 and a 4-month accuracy of 62% to 65%. The Rades model (c-statistic 0.44) and Bollen model (c statistic 0.70) had a 4-month accuracy of 69% and 75%, respectively. CONCLUSION: The Bollen model performs better than the other models. However, improvements are still warranted to increase the accuracy. LEVEL OF EVIDENCE: 3. PMID- 26866743 TI - Letters. PMID- 26866744 TI - Letters. PMID- 26866745 TI - To the Editor. PMID- 26866746 TI - Imaging Features of Biphenotypic Primary Liver Carcinoma (Hepatocholangiocarcinoma) and the Potential to Mimic Hepatocellular Carcinoma: LI-RADS Analysis of CT and MRI Features in 61 Cases. AB - OBJECTIVE: The purpose of this study was to determine the frequency with which biphenotypic primary liver carcinoma (also called hepatocholangiocarcinoma) may be misclassified as hepatocellular carcinoma (HCC) when only Liver Imaging Reporting and Data System (LI-RADS) major features are used and after consideration of ancillary features. MATERIALS AND METHODS: A review of all pathologically proven biphenotypic primary liver carcinomas diagnosed at one institution from 2006 to 2014 was performed. Two subspecialized abdominal imagers independently reviewed cases using LI-RADS version 2014 and assigned major features, ancillary features, and additional findings. The number of lesions meeting imaging criteria for HCC was determined after assessment of major features alone and after the addition of ancillary features. RESULTS: Sixty-one patients (30 men, 31 women; mean age, 62 years; range, 22-89 years) with biphenotypic primary liver carcinomas who underwent pretreatment multiphasic contrast-enhanced MRI (48 patients) or CT (13 patients) were included. According to LI-RADS major features alone, 33 (54.1%) lesions met criteria for HCC and therefore might have been misclassified. Thirteen had arterial phase hyperenhancement, washout, and a capsule. Twenty had arterial phase hyperenhancement with either washout (15 lesions) or a capsule (five lesions). After evaluation of ancillary features, 29 of these potential mimics exhibited at least one ancillary feature favoring non-HCC malignancy, possibly leading to appropriate reclassification. Of the four carcinomas that met criteria for HCC by major features and did not have ancillary features favoring non-HCC malignancy, two (3.3% of all tumors) fell within the Milan criteria. CONCLUSION: Most biphenotypic primary liver carcinomas have features of non-HCC malignancy and can be correctly categorized as such. Addition of ancillary features to major features may improve diagnostic accuracy over systems in which only major features are used. PMID- 26866747 TI - Association of KCNQ1 polymorphisms with gliclazide efficacy in Chinese type 2 diabetic patients. AB - OBJECTIVES: To investigate the effects of KCNQ1 polymorphisms on the efficacy of gliclazide in type 2 diabetic patients. MATERIALS AND METHODS: A total of 443 newly diagnosed type 2 diabetic patients were included in this study. After enrollment, patients went on an 8-week gliclazide monotherapy. Fasting plasma glucose (FPG) was measured before and after the treatment. Life-style information was collected by weekly follow-up. Genotyping of the two single-nucleotide polymorphisms was performed using the single base primer extension method. T test, one-way analysis of variance, and Pearson chi-test were used to evaluate the effects of rs2237892 and rs2237897 on the FPG reduction and treatment success rate. RESULTS: After 8 weeks of gliclazide therapy, the FPG decreased significantly from 10.9+/-2.8 to 7.4+/-2.2 mmol/l (P<0.001). Compared with the CC genotype, patients with CT or TT genotypes of rs2237897 achieved greater reduction in FPG (3.9+/-2.6 vs. 3.2+/-2.4 mmol/l, P=0.003; 33.9+/-19.0 vs. 27.7+/ 17.4%, P<0.001) and a higher rate of treatment success (74.1 vs. 65.2%, P=0.042 for criterion 1; 61.1 vs. 44.5%, P<0.001 for criterion 2, respectively), whereas no significant difference was found in the FPG reduction and treatment success rate among different genotypes of rs2237892. CONCLUSION: Our results indicated that a common variant of KCNQ1, rs2237897, was associated with the efficacy of gliclazide after 8-week monotherapy in Chinese newly diagnosed type 2 diabetic patients. The FPG reduction and treatment success rate were significantly higher in carriers of CT and TT genotypes. PMID- 26866749 TI - Interview with Michelle Arkin, PhD. PMID- 26866750 TI - Drug Discovery Approaches Utilizing Three-Dimensional Cell Culture. AB - Historically, two-dimensional (2D) cell culture has been the preferred method of producing disease models in vitro. Recently, there has been a move away from 2D culture in favor of generating three-dimensional (3D) multicellular structures, which are thought to be more representative of the in vivo environment. This transition has brought with it an influx of technologies capable of producing these structures in various ways. However, it is becoming evident that many of these technologies do not perform well in automated in vitro drug discovery units. We believe that this is a result of their incompatibility with high throughput screening (HTS). In this study, we review a number of technologies, which are currently available for producing in vitro 3D disease models. We assess their amenability with high-content screening and HTS and highlight our own work in attempting to address many of the practical problems that are hampering the successful deployment of 3D cell systems in mainstream research. PMID- 26866752 TI - Intracellularly Acid-Switchable Multifunctional Micelles for Combinational Photo/Chemotherapy of the Drug-Resistant Tumor. AB - The intrinsic or acquired drug resistance is the main challenge for cancer chemotherapy today. So far, many nanosized drug delivery systems (NDDS) have been exploited to combat cancer drug resistance. However, the therapy efficacy of current NDDS is severely impaired by the limited tumor penetration of the nanoparticles due to the existence of physiological and pathological barriers in the solid tumor. In this study, we report on the design and fabrication of intracellularly acid-switchable multifunctional micelles for combinational photo- and chemotherapy of the drug-resistant tumor. The micelles were composed of a pH responsive diblock copolymer, a photosensitizer, and a polymeric prodrug of doxorubicin. The micelle displayed silenced fluorescence and photoactivity during the blood circulation and switched to an active state in weakly acid conditions (i.e., pH <= 6.2) in the endocytic vesicles to dramatically induce a 7.5-fold increase of the fluorescence signal for fluorescence imaging. Upon near-infrared (NIR) laser irradiation, the micelle induced notable reactive oxygen species generation to trigger cytosol release of the chemotherapeutics and perform photodynamic therapy (PDT). Moreover, the micelle efficiently converted the NIR light to local heat for enhancing tumor penetration of the anticancer drug, tumor specific photothermal therapy, and photoacoustic (PA) imaging. Furthermore, the micelles could generate amplified magnetic resonance (MR) signal in an acidic microenvironment to perform MR imaging. Collectively, this study presents a robust nanoplatform for multimodal imaging and combinational therapy of the drug resistant tumor, which might provide an insight for developing polymer-based NDDS for cancer therapy. PMID- 26866753 TI - Head-Elevated Patient Positioning Decreases Complications of Emergent Tracheal Intubation in the Ward and Intensive Care Unit. AB - BACKGROUND: Based on the data from elective surgical patients, positioning patients in a back-up head-elevated position for preoxygenation and tracheal intubation can improve patient safety. However, data specific to the emergent setting are lacking. We hypothesized that back-up head-elevated positioning would be associated with a decrease in complications related to tracheal intubation in the emergency room environment. METHODS: This retrospective study was approved by the University of Washington Human Subjects Division (Seattle, WA). Eligible patients included all adults undergoing emergent tracheal intubation outside of the operating room by the anesthesiology-based airway service at 2 university affiliated teaching hospitals. All intubations were through direct laryngoscopy for an indication other than full cardiopulmonary arrest. Patient characteristics and details of the intubation procedure were derived from the medical record. The primary study endpoint was the occurrence of a composite of any intubation related complication: difficult intubation, hypoxemia, esophageal intubation, or pulmonary aspiration. Multivariable logistic regression was used to estimate the odds of the primary endpoint in the supine versus back-up head-elevated positions with adjustment for a priori-defined potential confounders (body mass index and a difficult intubation prediction score [Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non Anesthesiologist score]). RESULTS: Five hundred twenty-eight patients were analyzed. Overall, at least 1 intubation-related complication occurred in 76 of 336 (22.6%) patients managed in the supine position compared with 18 of 192 (9.3%) patients managed in the back-up head-elevated position. After adjusting for body mass index and the Mallampati, obstructive sleep Apnea, Cervical mobility, mouth Opening, Coma, severe Hypoxemia, and intubation by a non Anesthesiologist score, the odds of encountering the primary endpoint during an emergency tracheal intubation in a back-up head-elevated position was 0.47 (95% confidence interval, 0.26-0.83; P = 0.01). CONCLUSIONS: Placing patients in a back-up head-elevated position, compared with supine position, during emergency tracheal intubation was associated with a reduced odds of airway-related complications. PMID- 26866754 TI - Build-up of toxic metals on the impervious surfaces of a commercial seaport. AB - In the context of increasing threats to the sensitive marine ecosystem by toxic metals, this study investigated the metal build-up on impervious surfaces specific to commercial seaports. The knowledge generated from this study will contribute to managing toxic metal pollution of the marine ecosystem. The study found that inter-modal operations and main access roadway had the highest loads followed by container storage and vehicle marshalling sites, while the quay line and short term storage areas had the lowest. Additionally, it was found that Cr, Al, Pb, Cu and Zn were predominantly attached to solids, while significant amount of Cu, Pb and Zn were found as nutrient complexes. As such, treatment options based on solids retention can be effective for some metal species, while ineffective for other species. Furthermore, Cu and Zn are more likely to become bioavailable in seawater due to their strong association with nutrients. Mathematical models to replicate the metal build-up process were also developed using experimental design approach and partial least squares regression. The models for Cr and Pb were found to be reliable, while those for Al, Zn and Cu were relatively less reliable, but could be employed for preliminary investigations. PMID- 26866755 TI - Genotoxicity assessment of particulate matter emitted from heavy-duty diesel powered vehicles using the in vivo Vicia faba L. micronucleus test. AB - Diesel exhaust particulate matter (PM) can have an impact on the environment due to its chemical constitution. A large number of substances such as organic compounds, sulfates, nitrogen derivatives and metals are adsorbed to the particles and desorption of these contaminants could promote genotoxic effects. The objective of this study was to assess the in vivo genotoxicity profile of diesel exhaust PM from heavy-duty engines. Extracts were obtained through leaching with pure water and chemical extraction using three organic solvents (dichloromethane, hexane, and acetone). The in vivo Vicia faba micronucleus test (ISO 29200 protocol) was used to assess the environmental impact of the samples collected from diesel exhaust PM. The solid diesel PM (soot) dissolved in water, and the different extracts, showed positive results for micronucleus formation. After the addition of EDTA, the aqueous extracts did not show a genotoxic effect. The absence of metals in the organic solvent extract indicated that organic compounds also had a genotoxic effect, which was not observed for a similar sample cleaned in a C18 column. Thus, considering the ecological importance of higher plants in relation to ecosystems (in contrast to Salmonella spp., which are commonly used in mutagenicity studies), the Vicia micronucleus test was demonstrated to be appropriate for complementing prokaryotic or in vitro tests on diesel exhaust particulate matter included in risk assessments. PMID- 26866756 TI - Chronic toxicity and physiological changes induced in the honey bee by the exposure to fipronil and Bacillus thuringiensis spores alone or combined. AB - In the agricultural environment, honey bees may be exposed to combinations of pesticides. Until now, the effects of these combinations on honey bee health have been poorly investigated. In this study, we assessed the impacts of biological and chemical insecticides, combining low dietary concentrations of Bacillus thuringiensis (Bt) spores (100 and 1000ug/L) with the chemical insecticide fipronil (1ug/L). In order to assess the possible effects of Cry toxins, the Bt kurstaki strain (Btk) was compared with a Bt strain devoid of toxin-encoding plasmids (Bt Cry(-)). The oral exposure to fipronil and Bt spores from both strains for 10 days did not elicit significant effects on the feeding behavior and survival after 25 days. Local and systemic physiological effects were investigated by measuring the activities of enzymes involved in the intermediary and detoxication metabolisms at two sampling dates (day 10 and day 20). Attention was focused on head and midgut glutathione-S-transferase (GST), midgut alkaline phosphatase (ALP), abdomen glyceraldehyde-3-phosphate dehydrogenase (GAPD) and glucose-6-phosphate dehydrogenase (G6PD). We found that Bt Cry(-) and Btk spores induced physiological modifications by differentially modulating enzyme activities. Fipronil influenced the enzyme activities differently at days 10 and 20 and, when combined with Bt spores, elicited modulations of some spore-induced physiological responses. These results show that an apparent absence of toxicity may hide physiological disruptions that could be potentially damaging for the bees, especially in the case of combined exposures to other environmental stressors. PMID- 26866757 TI - Physiological responses of Microcystis aeruginosa against the algicidal bacterium Pseudomonas aeruginosa. AB - Proliferation of cyanobacteria in aquatic ecosystems has caused water security problems throughout the world. Our preliminary study has showed that Pseudomonas aeruginosa can inhibit the growth of cyanobacterium, Microcystis aeruginosa. In order to explore the inhibitory mechanism of P. aeruginosa on the cell growth and synthesis of intracellular substances of M. aeruginosa, concentrations of Chlorophyll-a, intracellular protein, carbohydrate, enzyme activities and ion metabolism of M. aeruginosa, were investigated. The results indicated that 83.84% algicidal efficiency of P. aeruginosa was achieved after treatment for 7 days. The strain inhibited the reproduction of M. aeruginosa by impeding the synthesis of intracellular protein and carbohydrate of cyanobacterium, and only a very small part of intracellular protein and carbohydrate was detected after exposure to P. aeruginosa for 5 days. P. aeruginosa caused the alteration of intracellular antioxidant enzyme activity of M. aeruginosa, such as catalase, peroxidase. The accumulation of malondialdehyde aggravated membrane injury after treatment for 3 days. P. aeruginosa also affected the ion metabolism of cyanobacteria. The release of Na(+) and Cl(-) was significantly enhanced while the uptake of K(+), Ca(2+), Mg(2+), NO3(-) and SO4(2)(-) decreased. Surface morphology and intracellular structure of cyanobacteria and bacterial cells changed dramatically over time as evidenced by electron microscope (SEM) and transmission electron microscope (TEM) analysis. These results revealed that the algicidal activity of P. aeruginosa was primarily due to the fermentation liquid of P. aeruginosa that impeded the synthesis of intracellular protein and carbohydrate, and damaged the cell membrane through membrane lipid peroxidation. PMID- 26866758 TI - Kinetic characteristics and modeling of microalgae Chlorella vulgaris growth and CO2 biofixation considering the coupled effects of light intensity and dissolved inorganic carbon. AB - Understanding and optimizing the microalgae growth process is an essential prerequisite for effective CO2 capture using microalgae in photobioreactors. In this study, the kinetic characteristics of microalgae Chlorella vulgaris growth in response to light intensity and dissolved inorganic carbon (DIC) concentration were investigated. The greatest values of maximum biomass concentration (Xmax) and maximum specific growth rate (MUmax) were obtained as 2.303 g L(-1) and 0.078 h(-1), respectively, at a light intensity of 120 MUmol m(-2) s(-1) and DIC concentration of 17 mM. Based on the results, mathematical models describing the coupled effects of light intensity and DIC concentration on microalgae growth and CO2 biofixation are proposed. The models are able to predict the temporal evolution of C. vulgaris growth and CO2 biofixation rates from lag to stationary phases. Verification experiments confirmed that the model predictions agreed well with the experimental results. PMID- 26866759 TI - Microalgae from domestic wastewater facility's high rate algal pond: Lipids extraction, characterization and biodiesel production. AB - In this study, the harvesting of a biomass from a high rate algal pond (HRAP) of a real-scale domestic wastewater treatment facility and its potential as a biomaterial for the production of biodiesel were investigated. Increasing the medium pH to 12 induced high flocculation efficiency of up to 96% of the biomass through both sweep flocculation and charge neutralization. Lipids extracted by ultrasounds from this biomass contained around 70% of fatty acids, with palmitic and stearic acids being the most abundant. The extract obtained by supercritical CO2 contained 86% of fatty acids. Both conventional solvents extracts contained only around 10% of unsaturated fats, whereas supercritical CO2 extract contained more than 40% of unsaturated fatty acids. This same biomass was also subject to direct extractive-transesterification in a microwave reactor to produce fatty acid methyl esters, also known as, raw biodiesel. PMID- 26866760 TI - Co-digestion of food and garden waste with mixed sludge from wastewater treatment in continuously stirred tank reactors. AB - Co-digestions of urban organic waste were conducted to investigate the effect of the mixing ratio between sludge, food waste, grass clippings and green waste at different hydraulic retention times (HRTs). Compared to the digestion of 100% sludge, the methane yield increased by 48% and 35%, when co-digesting sludge with food waste, grass clippings and garden waste with a corresponding %VS of 10:67.5:15.75:6.75 (R1) and 10:45:31.5:13.5 (R2), respectively. The methane yield remained constant at around 425 and 385 NmL CH4/g VS in R1 and R2, respectively, when the reactors were operated at HRTs of 15, 20 and 30 days. However, the methane yield dropped significantly to 356 (R1) and 315 (R2) NmL CH4/g VS when reducing the HRT to 10 days, indicating that the process was stressed. Since the methane production rate improved significantly with decreasing HRT, the trade-off between yield and productivity was obtained at 15 days HRT. PMID- 26866761 TI - Cultivation of Neochloris oleoabundans in bubble column photobioreactor with or without localized deoxygenation. AB - This study evaluated long-term non-sterile cultivation of freshwater green alga Neochloris oleoabundans in a 15-liter bubble column photobioreactor (BCPBR) and the effects of a membrane-based localized oxygen remover (LOR) on deoxygenation, cell growth, and lipid production of N. oleoabundans. Batch and continuous cultivations were carried out under non-sterile conditions for 53 days with no detectable protozoa or other biological contaminants, indicating successful long term contamination-free cultivation. The results show that the BCPBR equipped with LOR (BCPBR-LOR) has enhanced deoxygenation efficiency and were able to maintain dissolved oxygen at a level of around 120% air saturation, which was 32% lower than that of the conventional BCPBR, which had no LOR. While similar biomass concentration and productivity were obtained in both systems, significantly higher lipid cell content and lipid productivity of microalgae were obtained in the latter, which was attributed to the low dO2 in culture due to enhanced deoxygenation efficiency of BCPBR-LOR. PMID- 26866762 TI - Cu2O Nanowire Photocathodes for Efficient and Durable Solar Water Splitting. AB - Due to its abundance, scalability, and nontoxicity, Cu2O has attracted extensive attention toward solar energy conversion, and it is the best performing metal oxide material. Until now, the high efficiency devices are all planar in structure, and their photocurrent densities still fall well below the theoretical value of 14.5 mA cm(-2) due to the incompatible light absorption and charge carrier diffusion lengths. Nanowire structures have been considered as a rational and promising approach to solve this issue, but due to various challenges, performance improvements through the use of nanowires have rarely been achieved. In this work, we develop a new synthetic method to grow Cu2O nanowire arrays on conductive fluorine-doped tin oxide substrates with well-controlled phase and excellent electronic and photonic properties. Also, we introduce an innovative blocking layer strategy to enable high performance. Further, through material engineering by combining a conformal nanoscale p-n junction, durable protective overlayer, and uniform catalyst decoration, we have successfully fabricated Cu2O nanowire array photocathodes for hydrogen generation from solar water splitting delivering unprecedentedly high photocurrent densities of 10 mA cm(-2) and stable operation beyond 50 h, establishing a new benchmark for metal oxide based photoelectrodes. PMID- 26866763 TI - Physical efficiency and activity energy expenditure in term pregnancy females measured during cardiopulmonary exercise tests with a supine cycle ergometer. AB - OBJECTIVES: To evaluate physical efficiency and activity energy expenditure (AEE) in term pregnancy females during cardiopulmonary exercise tests with a supine cycle ergometer. MATERIAL AND METHODS: The study comprised 22 healthy full-term pregnancy women with uncomplicated pregnancies hospitalized in the Department of Gynecology and Obstetrics, Specialist Teaching Hospital in Tychy, Poland. All subjects underwent cardiopulmonary exercise tests (CPET) on a supine cycle ergometer. The 12-min, three-stage, progressive, symptom-limited submaximal test protocol (up to 80% HRmax) was used. Pulsometry was used to record HR on a beat to-beat analysis and to calculate AEE. Respiratory responses were measured by ergospirometer and a computer system on a breath-by-breath basis at rest, during exercise and at restitution. RESULTS: In the studied population, VO2max was established at the level of 2.19 +/- 0.33 L/min in ergospirometry and 2.04 +/- 025 L/min in pulsometry. Physical efficiency calculated for sub-maximal exercise by use of the Davis equation was 30.52 +/- 0.12%. AEE, based on VO2 in various phases of the CPET, was 0.47, 0.71 and 0.88 L/min for phases 25, 50 and 75 W. Based on ergospirometer readouts, AEE was 10.60, 16.11 and 20.94 kJ/min for phases 25, 50 and 75 W. Overall mean AEE (determined by pulsometry) was 10.59 kJ/min. CPET testing did not have any negative effect upon the health or life of the neonates involved in the study. CONCLUSIONS: Submaximal CPET up to 80% HRmax with a supine cycle ergometer is a safe and precise method for assessing work efficiency in term pregnancy women. PMID- 26866764 TI - Readers of narratives take the protagonist's geographical perspective. Evidence from an event-related potential study. AB - This ERP study explores how the reader's brain is sensitive to the protagonist's perspective in the fictitious environment of narratives. Participants initially received narratives describing a protagonist living in a given geographical place. Later on they were given short paragraphs describing another character as "coming" or "going" to a place either close to or distant from the protagonist. Paragraphs referring to distant places elicited larger negative waves than those with places close to the protagonist. Moreover, narratives with the verb to come incoherent with the protagonist's perspective (e.g., "she came to the distant place") elicited larger negative-going waves in the 320-400ms time window than coherent paragraphs (e.g., "she came to the close place"). These results indicate that readers of narratives were able to take the protagonist's geographical perspective, showing discourse-level coherence effects when they read motion sentences with the marked deictic verb to come. PMID- 26866765 TI - Gene expression in large pedigrees: analytic approaches. AB - BACKGROUND: We currently have the ability to quantify transcript abundance of messenger RNA (mRNA), genome-wide, using microarray technologies. Analyzing genotype, phenotype and expression data from 20 pedigrees, the members of our Genetic Analysis Workshop (GAW) 19 gene expression group published 9 papers, tackling some timely and important problems and questions. To study the complexity and interrelationships of genetics and gene expression, we used established statistical tools, developed newer statistical tools, and developed and applied extensions to these tools. METHODS: To study gene expression correlations in the pedigree members (without incorporating genotype or trait data into the analysis), 2 papers used principal components analysis, weighted gene coexpression network analysis, meta-analyses, gene enrichment analyses, and linear mixed models. To explore the relationship between genetics and gene expression, 2 papers studied expression quantitative trait locus allelic heterogeneity through conditional association analyses, and epistasis through interaction analyses. A third paper assessed the feasibility of applying allele specific binding to filter potential regulatory single-nucleotide polymorphisms (SNPs). Analytic approaches included linear mixed models based on measured genotypes in pedigrees, permutation tests, and covariance kernels. To incorporate both genotype and phenotype data with gene expression, 4 groups employed linear mixed models, nonparametric weighted U statistics, structural equation modeling, Bayesian unified frameworks, and multiple regression. RESULTS AND DISCUSSION: Regarding the analysis of pedigree data, we found that gene expression is familial, indicating that at least 1 factor for pedigree membership or multiple factors for the degree of relationship should be included in analyses, and we developed a method to adjust for familiality prior to conducting weighted co expression gene network analysis. For SNP association and conditional analyses, we found FaST-LMM (Factored Spectrally Transformed Linear Mixed Model) and SOLAR MGA (Sequential Oligogenic Linkage Analysis Routines -Major Gene Analysis) have similar type 1 and type 2 errors and can be used almost interchangeably. To improve the power and precision of association tests, prior knowledge of DNase-I hypersensitivity sites or other relevant biological annotations can be incorporated into the analyses. On a biological level, eQTL (expression quantitative trait loci) are genetically complex, exhibiting both allelic heterogeneity and epistasis. Including both genotype and phenotype data together with measurements of gene expression was found to be generally advantageous in terms of generating improved levels of significance and in providing more interpretable biological models. CONCLUSIONS: Pedigrees can be used to conduct analyses of and enhance gene expression studies. PMID- 26866766 TI - Cognitively Engaging Chronic Physical Activity, But Not Aerobic Exercise, Affects Executive Functions in Primary School Children: A Group-Randomized Controlled Trial. AB - Although the positive effects of different kinds of physical activity (PA) on cognitive functioning have already been demonstrated in a variety of studies, the role of cognitive engagement in promoting children's executive functions is still unclear. The aim of the current study was therefore to investigate the effects of two qualitatively different chronic PA interventions on executive functions in primary school children. Children (N = 181) aged between 10 and 12 years were assigned to either a 6-week physical education program with a high level of physical exertion and high cognitive engagement (team games), a physical education program with high physical exertion but low cognitive engagement (aerobic exercise), or to a physical education program with both low physical exertion and low cognitive engagement (control condition). Executive functions (updating, inhibition, shifting) and aerobic fitness (multistage 20-m shuttle run test) were measured before and after the respective condition. Results revealed that both interventions (team games and aerobic exercise) have a positive impact on children's aerobic fitness (4-5% increase in estimated VO2max). Importantly, an improvement in shifting performance was found only in the team games and not in the aerobic exercise or control condition. Thus, the inclusion of cognitive engagement in PA seems to be the most promising type of chronic intervention to enhance executive functions in children, providing further evidence for the importance of the qualitative aspects of PA. PMID- 26866767 TI - Transtheoretical Principles and Processes for Adopting Physical Activity: A Longitudinal 24-Month Comparison of Maintainers, Relapsers, and Nonchangers. AB - This study examined longitudinal differences in use of transtheoretical model (TTM) behavior change constructs in maintainers (who reached and maintained exercise guidelines), relapsers (who reached guidelines, then regressed), and nonchangers (who did not reach guidelines). Data from two population-based TTM tailored randomized trial intervention groups targeting exercise behavior (N = 1050) were pooled, and analyses assessed differences in TTM constructs between the three groups at baseline, 12 months, and 24 months. Findings indicated that relapsers tended to use TTM variables similarly to maintainers with the exception of self-efficacy, consciousness raising, and most behavioral processes of change, at 24 months. Nonchangers, however, used all TTM variables less than maintainers at nearly every time point. Findings suggest that relapsers remain more active than nonchangers in terms of use of change processes. Poor response to interventions (nonchangers) may be predicted by low baseline engagement in change processes. Although relapsers reverted to physical inactivity, their overall greater use of TTM constructs suggests that their efforts to change remain better than those of the stable nonchanger group. Future research can focus on treatment engagement strategies to help the stable nonchangers initiate change and to help relapsers to maintain treatment gains. PMID- 26866768 TI - Differences in Attentional Focus Associated With Recovery From Sports Injury: Does Injury Induce an Internal Focus? AB - Although it is commonly believed that focusing too much attention on the injured body area impairs recovery in sports, this has not been directly assessed. The present study investigated attentional focus following sports injury. Experienced baseball position players recovering from knee surgery (Expt 1) and baseball pitchers recovering from elbow surgery (Expt 2) performed simulated batting and pitching respectively. They also performed three different secondary tasks: leg angle judgments, arm angle judgments, and judgments about the ball leaving their bat/hand. Injured athletes were compared with expert and novice control groups. Performance on the secondary tasks indicated that the injured batters had an internal focus of attention localized on the area of the injury resulting in significantly poorer batting performance as compared with the expert controls. Injured pitchers had a diffuse, internal attentional focus similar to that of novices resulting in poorer pitching performance as compared with the expert controls. PMID- 26866769 TI - Do Male And Female Cyclists' Cortical Activity Differ Before and During Cycling Exercise? AB - Although men and women are suggested to vary in resistance to fatigue, possible sex difference in its central component have rarely been investigated via electroencephalography (EEG). Therefore, we examined differences in cortical activity between male and female cyclists (n = 26) during cycling exercise. Participants performed an incremental test to derive the anaerobic threshold from the lactate power curve. In addition, cyclists' cortical activity was recorded with EEG before and during cycling exercise. Whereas women showed higher frontal alpha and beta activity at rest, no sex-specific differences of relative EEG spectral power occurred during cycling at higher intensity. Women and men's brains respond similarly during submaximal cycling, as both sexes show an inverted U-shaped curve of alpha power. Therefore, sex differences observable at rest vanish after the onset of exercise. PMID- 26866770 TI - Sensorimotor Rhythm Neurofeedback Enhances Golf Putting Performance. AB - Sensorimotor rhythm (SMR) activity has been related to automaticity during skilled action execution. However, few studies have bridged the causal link between SMR activity and sports performance. This study investigated the effect of SMR neurofeedback training (SMR NFT) on golf putting performance. We hypothesized that preelite golfers would exhibit enhanced putting performance after SMR NFT. Sixteen preelite golfers were recruited and randomly assigned into either an SMR or a control group. Participants were asked to perform putting while electroencephalogram (EEG) was recorded, both before and after intervention. Our results showed that the SMR group performed more accurately when putting and exhibited greater SMR power than the control group after 8 intervention sessions. This study concludes that SMR NFT is effective for increasing SMR during action preparation and for enhancing golf putting performance. Moreover, greater SMR activity might be an EEG signature of improved attention processing, which induces superior putting performance. PMID- 26866771 TI - rs6295 [C]-Allele Protects Against Depressive Mood in Elderly Endurance Athletes. AB - A single nucleotide variant within the promoter of the 5-hydroxytryptamine1A (5HT1A) receptor, rs6295, is part of a binding site for the transcription factor. We aimed to ascertain whether the rs6295 mediates the effect of exercise on depressive mood in elderly endurance athletes. We prospectively enrolled 55 elderly athletes (marathon runners/bicyclists) and 58 controls. In a controlled, univariate model, an interaction between the [C]-allele and physical activity indicated that only among athletes, the variant resulting in an imperfect NUDR binding site was associated with a lower depression score. Hence, athletes presented with a significantly lower relative risk of achieving a suspicious depression score among carriers of at least one [C]-allele. Our results suggest that the positive effect of physical exercise on depressive mood might be mediated by the 5HT1A receptor and the extent of this protective effect seems to be enhanced by the [C]-allele of the rs6295 variant. PMID- 26866772 TI - Predictors of Moral Disengagement in Sport. AB - Researchers have made productive use of Bandura's (1991) construct of moral disengagement (MD) to help explain why sport participants deviate from ethical ideals. In this study of intercollegiate athletes from diverse sports (N = 713), we examined MD in relation to other character-related variables: empathy, moral identity, moral attentiveness, and contesting orientations. We also examined whether moral attentiveness conforms to the pattern of "bracketed morality" found in moral reasoning (Shields & Bredemeier, 1995) and moral behavior (Kavussanu, Boardley, Sagar, & Ring, 2013). Results indicated that MD correlated positively with perceptual moral attentiveness and war contesting orientation; MD correlated negatively with empathy, moral identity, reflective moral attentiveness, and partnership contesting orientation. Results of hierarchical regression demonstrated that gender, contesting orientations, moral identity, and one form of moral attentiveness were significant predictors of MD. Finally, sport participants were found to be less morally attentive in sport than in everyday life. PMID- 26866773 TI - To Weigh or Not to Weigh? Relation to Disordered Eating Attitudes and Behaviors Among Female Collegiate Athletes. AB - Female athletes have been identified as a subpopulation at heightened risk for disordered eating attitudes and behaviors, particularly due to weight pressures in their environment. Using a sample of 414 NCAA Division-I female collegiate athletes, we examined the relations of required team weigh-ins or self-weighing on disordered eating attitudes and behaviors. Through a series of multivariate analyses, we determined that team weighs were unrelated significantly to all outcome measures. Self-weighing, however, differentiated the athletes' scores on internalization, body satisfaction, dietary restraint, negative affect, and bulimic symptomatology; athletes who self-weighed three or more times a week (sometimes 1-2 times per week) reported significantly higher levels of pathology across all measures. Mandatory team-conducted weigh-ins appear to not be a salient pressure for female gymnasts and swimmer/divers, although the frequency of their self-weighing may represent a level of self-monitoring that is associated with greater endorsement of disordered eating attitudes and behaviors. PMID- 26866774 TI - Response-Order Effects in Survey Methods: A Randomized Controlled Crossover Study in the Context of Sport Injury Prevention. AB - Consistency tendency is characterized by the propensity for participants responding to subsequent items in a survey consistent with their responses to previous items. This method effect might contaminate the results of sport psychology surveys using cross-sectional design. We present a randomized controlled crossover study examining the effect of consistency tendency on the motivational pathway (i.e., autonomy support -> autonomous motivation -> intention) of self-determination theory in the context of sport injury prevention. Athletes from Sweden (N = 341) responded to the survey printed in either low interitem distance (IID; consistency tendency likely) or high IID (consistency tendency suppressed) on two separate occasions, with a one-week interim period. Participants were randomly allocated into two groups, and they received the survey of different IID at each occasion. Bayesian structural equation modeling showed that low IID condition had stronger parameter estimates than high IID condition, but the differences were not statistically significant. PMID- 26866776 TI - Frequency and clinical correlates of postural and striatal deformities in Parkinson's disease. AB - OBJECTIVE: To assess the frequency of postural and striatal deformities in patients with Parkinson's disease. PATIENTS AND METHODS: A total of 416 consecutive patients with Parkinson's disease were evaluated for musculoskeletal deformities using a standardized criteria. Data including disease history, motor complications and antiparkinsonic treatment were collected. RESULTS: The overall frequency of musculoskeletal deformities was 19.7%. Striatal deformities were the most frequent deformities (9.9%). Scoliosis was the deformity most frequently found. No cases with Pisa syndrome or antecollis were found. Striatal deformities were associated with a younger age at onset, more frequent use of levodopa, as well as higher levodopa equivalent daily dose. Postural deformities were associated with higher motor scores. CONCLUSION: Postural and striatal deformities are common in Parkinson's disease. Striatal deformities appear to be more related to dopaminergic treatment, while postural deformities are associated with the motor state. PMID- 26866777 TI - Stroke and cardiac cell death: Two peas in a pod. AB - A close pathological link between stroke brain and heart failure may exist. Here, we discuss relevant laboratory and clinical reports demonstrating neural and cardiac myocyte cell death following ischemic stroke. Although various overlapping risk factors exist between cerebrovascular incidents and cardiac incidents, stroke therapy has largely neglected the cardiac pathological consequences. Recent preclinical stroke studies have implicated an indirect cell death pathway, involving toxic molecules, that originates from the stroke brain and produces cardiac cell death. In concert, previous laboratory reports have revealed a reverse cell death cascade, in that cardiac arrest leads to ischemic cell death in the brain. A deeper understanding of the crosstalk of cell death pathways between stroke and cardiac failure will facilitate the development of novel treatments designed to arrest the global pathology of both diseases thereby improving the clinical outcomes of patients diagnosed with stroke and heart failure. PMID- 26866779 TI - First-Principles Study of Antisite Defect Configurations in ZnGa2O4:Cr Persistent Phosphors. AB - Zinc gallate doped with chromium is a recently developed near-infrared emitting persistent phosphor, which is now extensively studied for in vivo bioimaging and security applications. The precise mechanism of this persistent luminescence relies on defects, in particular, on antisite defects and antisite pairs. A theoretical model combining the solid host, the dopant, and/or antisite defects is constructed to elucidate the mutual interactions in these complex materials. Energies of formation as well as dopant, and defect energies are calculated through density-functional theory simulations of large periodic supercells. The calculations support the chromium substitution on the slightly distorted octahedrally coordinated gallium site, and additional energy levels are introduced in the band gap of the host. Antisite pairs are found to be energetically favored over isolated antisites due to significant charge compensation as shown by calculated Hirshfeld-I charges. Significant structural distortions are found around all antisite defects. The local Cr surrounding is mainly distorted due to a ZnGa antisite. The stability analysis reveals that the distance between both antisites dominates the overall stability picture of the material containing the Cr dopant and an antisite pair. The findings are further rationalized using calculated densities of states and Hirshfeld-I charges. PMID- 26866778 TI - Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options. AB - The increasing prevalence of infections due to multidrug-resistant (MDR) gram negative bacteria constitutes a serious threat to global public health due to the limited treatment options available and the historically slow pace of development of new antimicrobial agents. Infections due to MDR strains are associated with increased morbidity and mortality and prolonged hospitalization, which translates to a significant burden on healthcare systems. In particular, MDR strains of Enterobacteriaceae (especially Klebsiella pneumoniae and Escherichia coli), Pseudomonas aeruginosa, and Acinetobacter baumannii have emerged as particularly serious concerns. In the United States, MDR strains of these organisms have been reported from hospitals throughout the country and are not limited to a small subset of hospitals. Factors that have contributed to the persistence and spread of MDR gram-negative bacteria include the following: overuse of existing antimicrobial agents, which has led to the development of adaptive resistance mechanisms by bacteria; a lack of good antimicrobial stewardship such that use of multiple broad-spectrum agents has helped perpetuate the cycle of increasing resistance; and a lack of good infection control practices. The rising prevalence of infections due to MDR gram-negative bacteria presents a significant dilemma in selecting empiric antimicrobial therapy in seriously ill hospitalized patients. A prudent initial strategy is to initiate treatment with a broad-spectrum regimen pending the availability of microbiological results allowing for targeted or narrowing of therapy. Empiric therapy with newer agents that exhibit good activity against MDR gram-negative bacterial strains such as tigecycline, ceftolozane-tazobactam, ceftazidime-avibactam, and others in the development pipeline offer promising alternatives to existing agents. PMID- 26866780 TI - The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release. AB - The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, MU >= 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful. PMID- 26866781 TI - Cognitive regulation of smoking behavior within a cigarette: Automatic and nonautomatic processes. AB - There has been limited research on cognitive processes governing smoking behavior in individuals who are tobacco dependent. In a replication (Baxter & Hinson, 2001) and extension, this study examined the theory (Tiffany, 1990) that drug use may be controlled by automatic processes that develop over repeated use. Heavy and occasional cigarette smokers completed a button-press reaction time (RT) task while concurrently smoking a cigarette, pretending to smoke a lit cigarette, or not smoking. Slowed RT during the button-press task indexed the cognitive disruption associated with nonautomatic control of behavior. Occasional smokers' RTs were slowed when smoking or pretending to smoke compared with when not smoking. Heavy smokers' RTs were slowed when pretending to smoke versus not smoking; however, their RTs were similarly fast when smoking compared with not smoking. The results indicated that smoking behavior was more highly regulated by controlled, nonautomatic processes among occasional smokers and by automatic processes among heavy smokers. Patterns of RT across the interpuff interval indicated that occasional smokers were significantly slowed in anticipation of and immediately after puffing onset, whereas heavy smokers were only slowed significantly after puffing onset. These findings suggest that the entirety of the smoking sequence becomes automatized, with the behaviors leading up to puffing becoming more strongly regulated by automatic processes with experience. These results have relevance to theories on the cognitive regulation of cigarette smoking and support the importance of interventions that focus on routinized behaviors that individuals engage in during and leading up to drug use. (PsycINFO Database Record PMID- 26866782 TI - Meta-analysis of the association between methamphetamine use and high-risk sexual behavior among heterosexuals. AB - A large body of research has found that nonheterosexual methamphetamine users engage in substantially higher levels of risky sex compared to nonusers. Considerably fewer studies have examined methamphetamine use and high-risk sex among heterosexuals. The present study is a meta-analysis of the empirical literature on methamphetamine use and high-risk sexual behavior among heterosexual individuals. Four risky sex outcomes were examined: unprotected vaginal intercourse, unprotected anal sex, inconsistent condom use, and sex with multiple partners. Analysis of 24 studies (26 independent samples) including 286,781 individuals found that the pooled mean weighted odds ratios ranged from 1.37 (unprotected vaginal intercourse) to 1.72 (inconsistent condom use), indicating that the odds of engaging in risky sex for heterosexual methamphetamine users is, on average, between 37% and 72% greater than for nonmethamphetamine users. Date of publication, percentage of White Caucasian respondents, and sample size were significant moderators of effect size magnitude. Moreover, symmetry plots revealed little direct evidence for publication bias. It is recommended that future research explore additional categorical and continuous variables as potential moderators of effect size strength. (PsycINFO Database Record PMID- 26866783 TI - Development of the Yale Food Addiction Scale Version 2.0. AB - Parallels in biological, psychological, and behavioral systems have led to the hypothesis that an addictive process may contribute to problematic eating. The Yale Food Addiction Scale (YFAS) was developed to provide a validated measure of addictive-like eating behavior based upon the diagnostic criteria for substance dependence. Recently, the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) was released, which included significant changes to the substance-related and addictive disorders (SRAD) section. In the current study, the YFAS 2.0 was developed to maintain consistency with the current diagnostic understanding of addiction and to improve the psychometric properties of the original YFAS. In a sample of 550 participants, 14.6% met criteria for food addiction. The YFAS 2.0 demonstrated good internal consistency, as well as convergent, discriminant, and incremental validity. Elevated scores on the YFAS 2.0 were associated with higher rates of obesity and more severe pathological eating (e.g., binge eating). The YFAS 2.0 also appeared to capture a related, but unique construct relative to traditional eating disorders. In a separate sample of 209 participants, the YFAS and YFAS 2.0 were directly compared. Both versions of the YFAS were similarly associated with elevated body mass index, binge eating, and weight cycling. However, exceeding the food addiction threshold was more strongly associated with obesity for the YFAS 2.0 than the original YFAS. Thus, the YFAS 2.0 appears to by a psychometrically sound measure that reflects the current diagnostic understanding of addiction to further investigate the potential role of an addictive process in problematic eating behavior. PMID- 26866785 TI - The origin of luminescence from di[4-(4-diphenylaminophenyl)phenyl]sulfone (DAPSF), a blue light emitter: an X-ray excited optical luminescence (XEOL) and X ray absorption near edge structure (XANES) study. AB - The electronic structure and optical properties of di[4-(4 diphenylaminophenyl)phenyl]sulfone (denoted as DAPSF), a highly efficient fluorophor, have been investigated using X-ray excited optical luminescence (XEOL) and X-ray absorption near edge structure (XANES) spectroscopy at excitation energies across the C, N, O K-edges and the sulfur K-edge. The results indicate that the blue luminescence is mainly related to the sulfur functional group. PMID- 26866784 TI - Formation of Kokumi-Enhancing gamma-Glutamyl Dipeptides in Parmesan Cheese by Means of gamma-Glutamyltransferase Activity and Stable Isotope Double-Labeling Studies. AB - Recently, gamma-glutamyl dipeptides (gamma-GPs) were found to be responsible for the attractive kokumi flavor of Parmesan cheese (PC). Quantitation of gamma-GPs and their parent amino acids in 13-, 24-, and 30-month ripened PC samples by LC MS/MS and stable isotope dilution analysis (SIDA), in-cheese (13)C-labeling studies, followed by analysis of the gamma-glutamyl transferase (GGT) activity revealed gamma-GPs to be generated most efficiently after 24 months of ripening by a GGT-catalyzed transfer of the gamma-glutamyl moiety of L-glutamine onto various acceptor amino acids released upon casein proteolysis. Following the identification of milk as a potential GGT source in PC, the functionality of the milk's GGT to generate the target gamma-GPs was validated by stable isotope double-labeling (SIDL) experiments. Therefore, raw and heat-treated milk samples were incubated with L-glutamine-[U-(13)C] and acceptor amino acids (X) and the hetero- (gamma-Glu-[(13)C5]-X) and homotranspeptidation products (gamma-Glu-Gln [(13)C10]) were quantitated by LC-MS/MS-SIDA using gamma-Glu-Ala-[(13)C3] as the internal standard. High GGT activity to generate the gamma-GPs and preference for L-phenylalanine and L-methionine as acceptor amino acids were found in raw milk and milk samples heat-treated for 10 min up to a maximum of 65 degrees C. In comparison, GGT activity and SIDL studies performed with inoculated Lactobacillus strains, including Lactobacillus harbinensis and Lactobacillus casei identified in PC by means of 16S rRNA gene sequencing, did not show any significant GGT activity and unequivocally demonstrated unpasteurized cow's milk, rather than microorganisms, as a key factor in gamma-glutamyl dipeptide generation in Parmesan cheese. PMID- 26866786 TI - Highly branched PtCu bimetallic alloy nanodendrites with superior electrocatalytic activities for oxygen reduction reactions. AB - Morphology control is a promising strategy to improve the catalytic performance of Pt-based catalysts. In this work, we reported a facile synthesis of PtCu bimetallic alloy nanodendrites using Brij 58 as a template. The highly branched structures and porous features offer relatively large surface areas, which is beneficial to the enhancement of the catalytic activity for oxygen reduction reactions in fuel cells. In addition, the elimination of carbon supports showed an important effect on the stability of the catalysts. By tuning the ratio of Pt and Cu precursors, PtCu nanodendrites were almost four times more active on the basis of an equivalent Pt mass for oxygen reduction reactions than the commercial Pt/C catalyst. PMID- 26866787 TI - Mixing Water, Transducing Energy, and Shaping Membranes: Autonomously Self Regulating Giant Vesicles. AB - Giant lipid vesicles are topologically closed compartments bounded by semipermeable flexible shells, which isolate femto- to picoliter quantities of the aqueous core from the surrounding bulk. Although water equilibrates readily across vesicular walls (10(-2)-10(-3) cm(3) cm(-2) s(-1)), the passive permeation of solutes is strongly hindered. Furthermore, because of their large volume compressibility (~10(9)-10(10) N m(-2)) and area expansion (10(2)-10(3) mN m(-1)) moduli, coupled with low bending rigidities (10(-19) N m), vesicular shells bend readily but resist volume compression and tolerate only a limited area expansion (~5%). Consequently, vesicles experiencing solute concentration gradients dissipate the available chemical energy through the osmotic movement of water, producing dramatic shape transformations driven by surface-area-volume changes and sustained by the incompressibility of water and the flexible membrane interface. Upon immersion in a hypertonic bath, an increased surface-area-volume ratio promotes large-scale morphological remodeling, reducing symmetry and stabilizing unusual shapes determined, at equilibrium, by the minimal bending energy configurations. By contrast, when subjected to a hypotonic bath, walls of giant vesicles lose their thermal undulation, accumulate mechanical tension, and, beyond a threshold swelling, exhibit remarkable oscillatory swell-burst cycles, with the latter characterized by damped, periodic oscillations in vesicle size, membrane tension, and phase behavior. This cyclical pattern of the osmotic influx of water, pressure, membrane tension, pore formation, and solute efflux suggests quasi-homeostatic self-regulatory behavior allowing vesicular compartments produced from simple molecular components, namely, water, osmolytes, and lipids, to sense and regulate their microenvironment in a negative feedback loop. PMID- 26866788 TI - Transparent capacitors with hybrid ZnO:Al and Ag nanowires as electrodes. AB - Transparent conducting films with a composite structure of AlZnO-Ag nanowires (AgNWs) have been prepared by atomic layer deposition. The sheet resistance was reduced from 120 to 9 Omega when the AgNW networks were involved. Transparent capacitors with Al2O3-TiO2-Al2O3 dielectrics were fabricated on the composite electrodes and demonstrated a capacitance density of 10.1 fF MUm(-2), which was significantly higher than that of capacitors with AlZnO electrodes (8.8 fF MUm( 1)). The capacitance density remained almost unchanged in a broad frequency range from 3 kHz to 1 MHz. Moreover, a low leakage current density of 2.4 * 10(-7) A cm(-2) at 1 V was achieved. Transparent and flexible capacitors were also fabricated using the composite electrodes, and demonstrated an improved bendability. The transparent capacitors showed an average optical transmittance over 70% in the visible range, and thus open the door to practical applications in transparent integrated circuits. PMID- 26866789 TI - Solid-phase synthesis of molecularly imprinted nanoparticles. AB - Molecularly imprinted polymers (MIPs) are synthetic materials, generally based on acrylic or methacrylic monomers, that are polymerized in the presence of a specific target molecule called the 'template' and capable of rebinding selectively to this target molecule. They have the potential to be low-cost and robust alternatives to biomolecules such as antibodies and receptors. When prepared by traditional synthetic methods (i.e., with free template in solution), their usefulness has been limited by high binding site heterogeneity, the presence of residual template and the fact that the production methods are complex and difficult to standardize. To overcome some of these limitations, we developed a method for the synthesis of MIP nanoparticles (nanoMIPs) using an innovative solid-phase approach, which relies on the covalent immobilization of the template molecules onto the surface of a solid support (glass beads). The obtained nanoMIPs are virtually free of template and demonstrate high affinity for the target molecule (e.g., melamine and trypsin in our published work). Because of an affinity separation step performed on the solid phase after polymerization, poor binders and unproductive polymer are removed, so the final product has more uniform binding characteristics. The overall protocol, starting from the immobilization of the template onto the solid phase and including the purification and characterization of the nanoparticles, takes up to 1 week. PMID- 26866793 TI - Gas-phase rapid reduction of graphene oxide through photoionization of gold nanoparticles. AB - This work introduces for the first time the rapid reduction of graphene oxide via the photoionization of gold nanoparticles in a continuous gas-phase process. Ejected electrons from gold nanoparticles facilitated the rapid photoinduced reduction of GO nanoflakes without the use of wet chemical processes. PMID- 26866792 TI - Procedures for the reconstruction, primary culture and experimental use of rainbow trout gill epithelia. AB - This protocol describes how to reconstruct and culture the freshwater rainbow trout gill epithelium on flat permeable membrane supports within cell culture inserts. The protocol describes gill cell isolation, cultured gill epithelium formation, maintenance, monitoring and preparation for use in experimental procedures. To produce a heterogeneous gill epithelium, as seen in vivo, seeding of isolated gill cells twice over a 2-d period is required. As a consequence, this is termed the double-seeded insert technique. Approximately 5-12 d after cell isolation and seeding, preparations develop electrically tight gill epithelia that can withstand freshwater on the apical cell surface. The system can be used to study freshwater gill physiology, and it is a humane alternative for toxicity testing, bioaccumulation studies and environmental water quality monitoring. PMID- 26866790 TI - Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. AB - This protocol describes a method to obtain spatially resolved proteomic maps of specific compartments within living mammalian cells. An engineered peroxidase, APEX2, is genetically targeted to a cellular region of interest. Upon the addition of hydrogen peroxide for 1 min to cells preloaded with a biotin-phenol substrate, APEX2 generates biotin-phenoxyl radicals that covalently tag proximal endogenous proteins. Cells are then lysed, and biotinylated proteins are enriched with streptavidin beads and identified by mass spectrometry. We describe the generation of an appropriate APEX2 fusion construct, proteomic sample preparation, and mass spectrometric data acquisition and analysis. A two-state stable isotope labeling by amino acids in cell culture (SILAC) protocol is used for proteomic mapping of membrane-enclosed cellular compartments from which APEX2 generated biotin-phenoxyl radicals cannot escape. For mapping of open cellular regions, we instead use a 'ratiometric' three-state SILAC protocol for high spatial specificity. Isotopic labeling of proteins takes 5-7 cell doublings. Generation of the biotinylated proteomic sample takes 1 d, acquiring the mass spectrometric data takes 2-5 d and analysis of the data to obtain the final proteomic list takes 1 week. PMID- 26866791 TI - Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method. AB - RNA digestions catalyzed by many ribonucleases generate RNA fragments that contain a 2',3'-cyclic phosphate (cP) at their 3' termini. However, standard RNA seq methods are unable to accurately capture cP-containing RNAs because the cP inhibits the adapter ligation reaction. We recently developed a method named cP RNA-seq that is able to selectively amplify and sequence cP-containing RNAs. Here we describe the cP-RNA-seq protocol in which the 3' termini of all RNAs, except those containing a cP, are cleaved through a periodate treatment after phosphatase treatment; hence, subsequent adapter ligation and cDNA amplification steps are exclusively applied to cP-containing RNAs. cP-RNA-seq takes ~6 d, excluding the time required for sequencing and bioinformatics analyses, which are not covered in detail in this protocol. Biochemical validation of the existence of cP in the identified RNAs takes ~3 d. Even though the cP-RNA-seq method was developed to identify angiogenin-generating 5'-tRNA halves as a proof of principle, the method should be applicable to global identification of cP containing RNA repertoires in various transcriptomes. PMID- 26866794 TI - Age-related invariance of abilities measured with the Wechsler Adult Intelligence Scale-IV. AB - Assessment of measurement invariance across populations is essential for meaningful comparison of test scores, and is especially relevant where repeated measurements are required for educational assessment or clinical diagnosis. Establishing measurement invariance legitimizes the assumption that test scores reflect the same psychological trait in different populations or across different occasions. Examination of Wechsler Adult Intelligence Scale-Fourth Edition (WAIS IV) U.S. standardization samples revealed that a first-order 5-factor measurement model was best fitting across 9 age groups from 16 years to 69 years. Strong metric invariance was found for 3 of 5 factors and partial intercept invariance for the remaining 2. Pairwise comparisons of adjacent age groups supported the inference that cognitive-trait group differences are manifested by group differences in the test scores. In educational and clinical settings these findings provide theoretical and empirical support to interpret changes in the index or subtest scores as reflecting changes in the corresponding cognitive abilities. Further, where clinically relevant, the subtest score composites can be used to compare changes in respective cognitive abilities. The model was supported in the Canadian standardization data with pooled age groups but the sample sizes were not adequate for detailed examination of separate age groups in the Canadian sample. (PsycINFO Database Record PMID- 26866795 TI - Are fearless dominance traits superfluous in operationalizing psychopathy? Incremental validity and sex differences. AB - Researchers are vigorously debating whether psychopathic personality includes seemingly adaptive traits, especially social and physical boldness. In a large sample (N = 1,565) of adult offenders, we examined the incremental validity of 2 operationalizations of boldness (Fearless Dominance traits in the Psychopathy Personality Inventory [Lilienfeld & Andrews, 1996]; Boldness traits in the triarchic model of psychopathy [Patrick, Fowles, & Krueger, 2009]), above and beyond other characteristics of psychopathy, in statistically predicting scores on 4 psychopathy-related measures, including the Psychopathy Checklist-Revised (PCL-R). The incremental validity added by boldness traits in predicting the PCL R's representation of psychopathy was especially pronounced for interpersonal traits (e.g., superficial charm, deceitfulness). Our analyses, however, revealed unexpected sex differences in the relevance of these traits to psychopathy, with boldness traits exhibiting reduced importance for psychopathy in women. We discuss the implications of these findings for measurement models of psychopathy. (PsycINFO Database Record PMID- 26866797 TI - Electrodeposited Co-doped NiSe2 nanoparticles film: a good electrocatalyst for efficient water splitting. AB - In this communication, we report that a Co-doped NiSe2 nanoparticles film electrodeposited on a conductive Ti plate (Co0.13Ni0.87Se2/Ti) behaves as a robust electrocatalyst for both HER and OER in strongly basic media, with good activity over a NiSe2/Ti counterpart. This Co0.13Ni0.87Se2/Ti catalytic electrode delivers 10 mA cm(-2) at an overpotential of 64 mV for HER and 100 mA cm(-2) at an overpotential of 320 mV for OER in 1.0 M KOH. A voltage of only 1.62 V is required to drive 10 mA cm(-2) for the two-electrode alkaline water electrolyzer using Co0.13Ni0.87Se2/Ti as an anode and cathode. PMID- 26866799 TI - CO Oxidation Prefers the Eley-Rideal or Langmuir-Hinshelwood Pathway: Monolayer vs Thin Film of SiC. AB - Using the first-principles approach, we investigated the electronic and chemical properties of wurtzite silicon carbide (2H-SiC) monolayer and thin film structures and substantiated their catalytic activity toward CO oxidation. 2H-SiC monolayer, being planar, is quite stable and has moderate binding with O2, while CO interacts physically; thus, the Eley-Rideal (ER) mechanism prevails over the Langmuir-Hinshelwood (LH) mechanism with an easily cleared activation barrier. Contrarily, 2H-SiC thin film, which exhibits a nonplanar structure, allows moderate binding of both CO and O2 on its surface, thus favoring the LH mechanism over the ER one. Comprehending these results leads to a better understanding of the reaction mechanisms involving structural contrast. Weak overlapping between the 2p(z)(C) and 3p(z)(Si) orbitals of the SiC monolayer system has been found to be the primary reason to revert the active site toward sp(3) hybridization, during interaction with the molecules. In addition, the influences of graphite and Ag(111) substrates on the CO oxidation mechanism were also studied, and it is observed that the ER mechanism is preserved on SiC/G system, while CO oxidation on the SiC/Ag(111) system follows the LH mechanism. The calculated Sabatier activities of the SiC catalysts show that the catalysts are very efficient in catalyzing CO oxidation. PMID- 26866796 TI - Development of an itemwise efficiency scoring method: Concurrent, convergent, discriminant, and neuroimaging-based predictive validity assessed in a large community sample. AB - Traditional "paper-and-pencil" testing is imprecise in measuring speed and hence limited in assessing performance efficiency, but computerized testing permits precision in measuring itemwise response time. We present a method of scoring performance efficiency (combining information from accuracy and speed) at the item level. Using a community sample of 9,498 youths age 8-21, we calculated item level efficiency scores on 4 neurocognitive tests, and compared the concurrent, convergent, discriminant, and predictive validity of these scores with simple averaging of standardized speed and accuracy-summed scores. Concurrent validity was measured by the scores' abilities to distinguish men from women and their correlations with age; convergent and discriminant validity were measured by correlations with other scores inside and outside of their neurocognitive domains; predictive validity was measured by correlations with brain volume in regions associated with the specific neurocognitive abilities. Results provide support for the ability of itemwise efficiency scoring to detect signals as strong as those detected by standard efficiency scoring methods. We find no evidence of superior validity of the itemwise scores over traditional scores, but point out several advantages of the former. The itemwise efficiency scoring method shows promise as an alternative to standard efficiency scoring methods, with overall moderate support from tests of 4 different types of validity. This method allows the use of existing item analysis methods and provides the convenient ability to adjust the overall emphasis of accuracy versus speed in the efficiency score, thus adjusting the scoring to the real-world demands the test is aiming to fulfill. (PsycINFO Database Record PMID- 26866801 TI - Collaboration Expertise in Medicine - No Evidence for Cross-Domain Application from a Memory Retrieval Study. AB - BACKGROUND: Is there evidence for expertise on collaboration and, if so, is there evidence for cross-domain application? Recall of stimuli was used to measure so called internal collaboration scripts of novices and experts in two studies. Internal collaboration scripts refer to an individual's knowledge about how to interact with others in a social situation. METHOD- STUDY 1: Ten collaboration experts and ten novices of the content domain social science were presented with four pictures of people involved in collaborative activities. The recall texts were coded, distinguishing between superficial and collaboration script information. RESULTS- STUDY 1: Experts recalled significantly more collaboration script information (M = 25.20; SD = 5.88) than did novices (M = 13.80; SD = 4.47). Differences in superficial information were not found. STUDY 2: Study 2 tested whether the differences found in Study 1 could be replicated. Furthermore, the cross-domain application of internal collaboration scripts was explored. METHOD- STUDY 2: Twenty collaboration experts and 20 novices of the content domain medicine were presented with four pictures and four videos of their content domain and a video and picture of another content domain. All stimuli showed collaborative activities typical for the respective content domains. RESULTS- STUDY 2: As in Study 1, experts recalled significantly more collaboration script information of their content domain (M = 71.65; SD = 33.23) than did novices (M = 54.25; SD = 15.01). For the novices, no differences were found for the superficial information nor for the retrieval of collaboration script information recalled after the other content domain stimuli. DISCUSSION: There is evidence for expertise on collaboration in memory tasks. The results show that experts hold substantially more collaboration script information than did novices. Furthermore, the differences between collaboration novices and collaboration experts occurred only in their own content domain, indicating that internal collaboration scripts are not easily stored and retrieved in memory tasks other than in the own content domain. PMID- 26866800 TI - Experimental Approach Reveals the Role of alx1 in the Evolution of the Echinoderm Larval Skeleton. AB - Over the course of evolution, the acquisition of novel structures has ultimately led to wide variation in morphology among extant multicellular organisms. Thus, the origins of genetic systems for new morphological structures are a subject of great interest in evolutionary biology. The larval skeleton is a novel structure acquired in some echinoderm lineages via the activation of the adult skeletogenic machinery. Previously, VEGF signaling was suggested to have played an important role in the acquisition of the larval skeleton. In the present study, we compared expression patterns of Alx genes among echinoderm classes to further explore the factors involved in the acquisition of a larval skeleton. We found that the alx1 gene, originally described as crucial for sea urchin skeletogenesis, may have also played an essential role in the evolution of the larval skeleton. Unlike those echinoderms that have a larval skeleton, we found that alx1 of starfish was barely expressed in early larvae that have no skeleton. When alx1 overexpression was induced via injection of alx1 mRNA into starfish eggs, the expression patterns of certain genes, including those possibly involved in skeletogenesis, were altered. This suggested that a portion of the skeletogenic program was induced solely by alx1. However, we observed no obvious external phenotype or skeleton. We concluded that alx1 was necessary but not sufficient for the acquisition of the larval skeleton, which, in fact, requires several genetic events. Based on these results, we discuss how the larval expression of alx1 contributed to the acquisition of the larval skeleton in the putative ancestral lineage of echinoderms. PMID- 26866802 TI - Next-Generation Sequencing of Aquatic Oligochaetes: Comparison of Experimental Communities. AB - Aquatic oligochaetes are a common group of freshwater benthic invertebrates known to be very sensitive to environmental changes and currently used as bioindicators in some countries. However, more extensive application of oligochaetes for assessing the ecological quality of sediments in watercourses and lakes would require overcoming the difficulties related to morphology-based identification of oligochaetes species. This study tested the Next-Generation Sequencing (NGS) of a standard cytochrome c oxydase I (COI) barcode as a tool for the rapid assessment of oligochaete diversity in environmental samples, based on mixed specimen samples. To know the composition of each sample we Sanger sequenced every specimen present in these samples. Our study showed that a large majority of OTUs (Operational Taxonomic Unit) could be detected by NGS analyses. We also observed congruence between the NGS and specimen abundance data for several but not all OTUs. Because the differences in sequence abundance data were consistent across samples, we exploited these variations to empirically design correction factors. We showed that such factors increased the congruence between the values of oligochaetes-based indices inferred from the NGS and the Sanger-sequenced specimen data. The validation of these correction factors by further experimental studies will be needed for the adaptation and use of NGS technology in biomonitoring studies based on oligochaete communities. PMID- 26866803 TI - Epigenetic Roulette in Blood Stream Plasmodium: Gambling on Sex. PMID- 26866804 TI - Skin grafting and tissue replacement for treating foot ulcers in people with diabetes. AB - BACKGROUND: Foot ulceration is a major problem in people with diabetes and is the leading cause of hospitalisation and limb amputations. Skin grafts and tissue replacements can be used to reconstruct skin defects for people with diabetic foot ulcers in addition to providing them with standard care. Skin substitutes can consist of bioengineered or artificial skin, autografts (taken from the patient), allografts (taken from another person) or xenografts (taken from animals). OBJECTIVES: To determine the benefits and harms of skin grafting and tissue replacement for treating foot ulcers in people with diabetes. SEARCH METHODS: In April 2015 we searched: The Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We also searched clinical trial registries to identify ongoing studies. We did not apply restrictions to language, date of publication or study setting. SELECTION CRITERIA: Randomised clinical trials (RCTs) of skin grafts or tissue replacements for treating foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the quality of the included studies. MAIN RESULTS: We included seventeen studies with a total of 1655 randomised participants in this review. Risk of bias was variable among studies. Blinding of participants, personnel and outcome assessment was not possible in most trials because of obvious differences between the treatments. The lack of a blinded outcome assessor may have caused detection bias when ulcer healing was assessed. However, possible detection bias is hard to prevent due to the nature of the skin replacement products we assessed, and the fact that they are easily recognisable. Strikingly, nearly all studies (15/17) reported industry involvement; at least one of the authors was connected to a commercial organisation or the study was funded by a commercial organisation. In addition, the funnel plot for assessing risk of bias appeared to be asymmetrical; suggesting that small studies with 'negative' results are less likely to be published.Thirteen of the studies included in this review compared a skin graft or tissue replacement with standard care. Four studies compared two grafts or tissue replacements with each other. When we pooled the results of all the individual studies, the skin grafts and tissue replacement products that were used in the trials increased the healing rate of foot ulcers in patients with diabetes compared to standard care (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.30 to 1.85, low quality of evidence). However, the strength of effect was variable depending on the specific product that was used (e.g. EpiFix(r) RR 11.08, 95% CI 1.69 to 72.82 and OrCel(r) RR 1.75, 95% CI 0.61 to 5.05). Based on the four included studies that directly compared two products, no specific type of skin graft or tissue replacement showed a superior effect on ulcer healing over another type of skin graft or tissue replacement.Sixteen of the included studies reported on adverse events in various ways. No study reported a statistically significant difference in the occurrence of adverse events between the intervention and the control group.Only two of the included studies reported on total incidence of lower limb amputations. We found fewer amputations in the experimental group compared with the standard care group when we pooled the results of these two studies, although the absolute risk reduction for amputation was small (RR 0.43, 95% CI 0.23 to 0.81; risk difference (RD) -0.06, 95% CI -0.10 to -0.01, very low quality of evidence). AUTHORS' CONCLUSIONS: Based on the studies included in this review, the overall therapeutic effect of skin grafts and tissue replacements used in conjunction with standard care shows an increase in the healing rate of foot ulcers and slightly fewer amputations in people with diabetes compared with standard care alone. However, the data available to us was insufficient for us to draw conclusions on the effectiveness of different types of skin grafts or tissue replacement therapies. In addition, evidence of long term effectiveness is lacking and cost-effectiveness is uncertain. PMID- 26866805 TI - Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes. AB - BACKGROUND: Spontaneous reports from patients able to report vascular sequelae in real time, and recognition that serum non transferrin bound iron may reach or exceed 10MUmol/L in the blood stream after iron tablets or infusions, led us to hypothesize that conventional iron treatments may provoke acute vascular injury. This prompted us to examine whether a phenotype could be observed in normal human endothelial cells treated with low dose iron. METHODOLOGY: Confluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrate or fresh media for RNA sequencing and validation studies. RNA transcript profiles were evaluated using directional RNA sequencing with no pre specification of target sequences. Alignments were counted for exons and junctions of the gene strand only, blinded to treatment types. PRINCIPAL FINDINGS: Rapid changes in RNA transcript profiles were observed in endothelial cells treated with 10MUmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology (GO) performed on all differentially expressed genes revealed significant differences in biological process terms between iron and media-treated EC, whereas 10 sets of an equivalent number of randomly selected genes from the respective EC gene datasets showed no significant differences in any GO terms. After 1 hour, differentially expressed genes clustered to vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016, 0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulus most significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10MUM iron treatment elicited DNA damage within 1 hour. This was accompanied by a brisk DNA damage response pulse, as ascertained by the development of DNA damage response (DDR) foci, and p53 stabilization. SIGNIFICANCE: These data suggest that low dose iron treatments are sufficient to modify the vascular endothelium, and induce a DNA damage response. PMID- 26866806 TI - On the Origins and Control of Community Types in the Human Microbiome. AB - Microbiome-based stratification of healthy individuals into compositional categories, referred to as "enterotypes" or "community types", holds promise for drastically improving personalized medicine. Despite this potential, the existence of community types and the degree of their distinctness have been highly debated. Here we adopted a dynamic systems approach and found that heterogeneity in the interspecific interactions or the presence of strongly interacting species is sufficient to explain community types, independent of the topology of the underlying ecological network. By controlling the presence or absence of these strongly interacting species we can steer the microbial ecosystem to any desired community type. This open-loop control strategy still holds even when the community types are not distinct but appear as dense regions within a continuous gradient. This finding can be used to develop viable therapeutic strategies for shifting the microbial composition to a healthy configuration. PMID- 26866808 TI - Enhanced Bifunctional Oxygen Catalysis in Strained LaNiO3 Perovskites. AB - Strain is known to greatly influence low-temperature oxygen electrocatalysis on noble metal films, leading to significant enhancements in bifunctional activity essential for fuel cells and metal-air batteries. However, its catalytic impact on transition-metal oxide thin films, such as perovskites, is not widely understood. Here, we epitaxially strain the conducting perovskite LaNiO3 to systematically determine its influence on both the oxygen reduction and oxygen evolution reaction. Uniquely, we found that compressive strain could significantly enhance both reactions, yielding a bifunctional catalyst that surpasses the performance of noble metals such as Pt. We attribute the improved bifunctionality to strain-induced splitting of the eg orbitals, which can customize orbital asymmetry at the surface. Analogous to strain-induced shifts in the d-band center of noble metals relative to the Fermi level, such splitting can dramatically affect catalytic activity in this perovskite and other potentially more active oxides. PMID- 26866807 TI - Effect of Subliminal Lexical Priming on the Subjective Perception of Images: A Machine Learning Approach. AB - The purpose of the study is to examine the effect of subliminal priming in terms of the perception of images influenced by words with positive, negative, and neutral emotional content, through electroencephalograms (EEGs). Participants were instructed to rate how much they like the stimuli images, on a 7-point Likert scale, after being subliminally exposed to masked lexical prime words that exhibit positive, negative, and neutral connotations with respect to the images. Simultaneously, the EEGs were recorded. Statistical tests such as repeated measures ANOVAs and two-tailed paired-samples t-tests were performed to measure significant differences in the likability ratings among the three prime affect types; the results showed a strong shift in the likeness judgment for the images in the positively primed condition compared to the other two. The acquired EEGs were examined to assess the difference in brain activity associated with the three different conditions. The consistent results obtained confirmed the overall priming effect on participants' explicit ratings. In addition, machine learning algorithms such as support vector machines (SVMs), and AdaBoost classifiers were applied to infer the prime affect type from the ERPs. The highest classification rates of 95.0% and 70.0% obtained respectively for average-trial binary classifier and average-trial multi-class further emphasize that the ERPs encode information about the different kinds of primes. PMID- 26866809 TI - Microtubule and Actin Interplay Drive Intracellular c-Src Trafficking. AB - The proto-oncogene c-Src is involved in a variety of signaling processes. Therefore, c-Src spatiotemporal localization is critical for interaction with downstream targets. However, the mechanisms regulating this localization have remained elusive. Previous studies have shown that c-Src trafficking is a microtubule-dependent process that facilitates c-Src turnover in neuronal growth cones. As such, microtubule depolymerization lead to the inhibition of c-Src recycling. Alternatively, c-Src trafficking was also shown to be regulated by RhoB-dependent actin polymerization. Our results show that c-Src vesicles primarily exhibit microtubule-dependent trafficking; however, microtubule depolymerization does not inhibit vesicle movement. Instead, vesicular movement becomes both faster and less directional. This movement was associated with actin polymerization directly at c-Src vesicle membranes. Interestingly, it has been shown previously that c-Src delivery is an actin polymerization-dependent process that relies on small GTPase RhoB at c-Src vesicles. In agreement with this finding, microtubule depolymerization induced significant activation of RhoB, together with actin comet tail formation. These effects occurred downstream of GTP-exchange factor, GEF-H1, which was released from depolymerizing MTs. Accordingly, GEF-H1 activity was necessary for actin comet tail formation at the Src vesicles. Our results indicate that regulation of c-Src trafficking requires both microtubules and actin polymerization, and that GEF-H1 coordinates c-Src trafficking, acting as a molecular switch between these two mechanisms. PMID- 26866810 TI - Ovarian Function, Not Age, Predicts the Benefit from Ovarian Suppression or Ablation for Premenopausal Women with Breast Cancer. AB - The role of adjuvant ovarian suppression or ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer remains controversial. The purpose of our study was to examine which patients might benefit from the addition of OS/OA to tamoxifen. We analyzed the data of 2065 premenopausal patients with hormone receptor-positive invasive ductal carcinomas who were treated at Sun Yat-Sen University Cancer Center from 2000 to 2008. The five-year disease-free survival rate (DFSR) and overall survival rate (OSR) were compared by menstrual status and treatment. Compared with patients older than forty years of age, patients younger than forty years old had significant lower DFSRs and OSRs. The addition of OS/OA to tamoxifen increased the DFSR and OSR of patients with normal menstrual cycles after chemotherapy, regardless of their age at diagnosis. Patients with normal menstrual cycles after chemotherapy are the main beneficiaries of an adjuvant OS/OA. PMID- 26866811 TI - Effects of Physiological Internal Noise on Model Predictions of Concurrent Vowel Identification for Normal-Hearing Listeners. AB - Previous studies have shown that concurrent vowel identification improves with increasing temporal onset asynchrony of the vowels, even if the vowels have the same fundamental frequency. The current study investigated the possible underlying neural processing involved in concurrent vowel perception. The individual vowel stimuli from a previously published study were used as inputs for a phenomenological auditory-nerve (AN) model. Spectrotemporal representations of simulated neural excitation patterns were constructed (i.e., neurograms) and then matched quantitatively with the neurograms of the single vowels using the Neurogram Similarity Index Measure (NSIM). A novel computational decision model was used to predict concurrent vowel identification. To facilitate optimum matches between the model predictions and the behavioral human data, internal noise was added at either neurogram generation or neurogram matching using the NSIM procedure. The best fit to the behavioral data was achieved with a signal-to noise ratio (SNR) of 8 dB for internal noise added at the neurogram but with a much smaller amount of internal noise (SNR of 60 dB) for internal noise added at the level of the NSIM computations. The results suggest that accurate modeling of concurrent vowel data from listeners with normal hearing may partly depend on internal noise and where internal noise is hypothesized to occur during the concurrent vowel identification process. PMID- 26866813 TI - Commentary on: "Game Maturity Model for Health Care". PMID- 26866812 TI - Synergistic Malaria Parasite Killing by Two Types of Plasmodial Surface Anion Channel Inhibitors. AB - Malaria parasites increase their host erythrocyte's permeability to a broad range of ions and organic solutes. The plasmodial surface anion channel (PSAC) mediates this uptake and is an established drug target. Development of therapies targeting this channel is limited by several problems including interactions between known inhibitors and permeating solutes that lead to incomplete channel block. Here, we designed and executed a high-throughput screen to identify a novel class of PSAC inhibitors that overcome this solute-inhibitor interaction. These new inhibitors differ from existing blockers and have distinct effects on channel-mediated transport, supporting a model of two separate routes for solute permeation though PSAC. Combinations of inhibitors specific for the two routes had strong synergistic action against in vitro parasite propagation, whereas combinations acting on a single route produced only additive effects. The magnitude of synergism depended on external nutrient concentrations, consistent with an essential role of the channel in parasite nutrient acquisition. The identified inhibitors will enable a better understanding of the channel's structure-function and may be starting points for novel combination therapies that produce synergistic parasite killing. PMID- 26866814 TI - Identification of an HV 1 voltage-gated proton channel in insects. AB - The voltage-gated proton channel 1 (HV 1) is an important component of the cellular proton extrusion machinery and is essential for charge compensation during the respiratory burst of phagocytes. HV 1 has been identified in a wide range of eukaryotes throughout the animal kingdom, with the exception of insects. Therefore, it has been proposed that insects do not possess an HV 1 channel. In the present study, we report the existence of an HV 1-type proton channel in insects. We searched insect transcriptome shotgun assembly (TSA) sequence databases and found putative HV 1 orthologues in various polyneopteran insects. To confirm that these putative HV 1 orthologues were functional channels, we studied the HV 1 channel of Nicoletia phytophila (NpHV 1), an insect of the Zygentoma order, in more detail. NpHV 1 comprises 239 amino acids and is 33% identical to the human voltage-gated proton channel 1. Patch clamp measurements in a heterologous expression system showed proton selectivity, as well as pH- and voltage-dependent gating. Interestingly, NpHV 1 shows slightly enhanced pH dependent gating compared to the human channel. Mutations in the first transmembrane segment at position 66 (Asp66), the presumed selectivity filter, lead to a loss of proton-selective conduction, confirming the importance of this aspartate residue in voltage-gated proton channels. DATABASE: Nucleotide sequence data have been deposited in the GenBank database under accession number KT780722. PMID- 26866816 TI - The 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Should Include New Standards for Hepatitis B Screening: Comment on the Article by Singh et al. PMID- 26866817 TI - Efficacy of probiotics in non-alcoholic fatty liver disease in adult and children: A meta-analysis of randomized controlled trials. AB - AIM: To evaluate the efficacy of probiotics in the treatment of adult and childhood non-alcoholic fatty liver disease (NAFLD). METHODS: Randomized controlled trials on the efficacy of probiotics in the treatment of adult and childhood NAFLD published before July 2015 were searched in multiple databases, including Cochrane Library, PubMed/MEDLINE, EBSCO, OVID, SCI, CNKI, and VIP. Article identification and data extraction were carried out by two reviewers based on the inclusion and exclusion criteria. RevMan 5.3 software was used for the meta-analysis. RESULTS: Nine randomized controlled trials with a total of 535 cases of NAFLD were included. Statistical differences in homeostasis model assessment, total cholesterol, high density lipoprotein, triglyceride, and tumor necrosis factor-alpha were detected between the probiotics and control groups with variations in different patient populations. No significant differences in body mass index (BMI), glucose, or insulin were detected between the two groups. Statistical differences in low density lipoprotein, alanine aminotransferase, aspartate transaminase, and BMI were detected between the two childhood groups (P <= 0.05). CONCLUSION: Probiotics provided improvements in the outcomes of homeostasis model assessment, total cholesterol, high density lipoprotein, and tumor necrosis factor-alpha in any NAFLD patients and triglyceride in Italian and Spanish patients, but no improvement in the outcomes of BMI, glucose, or insulin in adult NAFLD patients. The currently available data are not sufficient to compare the effects of probiotics between adult and childhood NAFLD patients. PMID- 26866818 TI - Sleep, Evolution and Brains. PMID- 26866815 TI - Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda. AB - BACKGROUND: Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Since the 1990s, Africa has accounted for the majority of reported human cases. In Uganda, plague cases occur in the West Nile region, near the border with Democratic Republic of Congo. Despite the ongoing risk of contracting plague in this region, little is known about Y. pestis genotypes causing human disease. METHODOLOGY/PRINCIPAL FINDINGS: During January 2004 December 2012, 1,092 suspect human plague cases were recorded in the West Nile region of Uganda. Sixty-one cases were culture-confirmed. Recovered Y. pestis isolates were analyzed using three typing methods, single nucleotide polymorphisms (SNPs), pulsed field gel electrophoresis (PFGE), and multiple variable number of tandem repeat analysis (MLVA) and subpopulations analyzed in the context of associated geographic, temporal, and clinical data for source patients. All three methods separated the 61 isolates into two distinct 1.ANT lineages, which persisted throughout the 9 year period and were associated with differences in elevation and geographic distribution. CONCLUSIONS/SIGNIFICANCE: We demonstrate that human cases of plague in the West Nile region of Uganda are caused by two distinct 1.ANT genetic subpopulations. Notably, all three typing methods used, SNPs, PFGE, and MLVA, identified the two genetic subpopulations, despite recognizing different mutation types in the Y. pestis genome. The geographic and elevation differences between the two subpopulations is suggestive of their maintenance in highly localized enzootic cycles, potentially with differing vector-host community composition. This improved understanding of Y. pestis subpopulations in the West Nile region will be useful for identifying ecologic and environmental factors associated with elevated plague risk. PMID- 26866819 TI - Hepatocellular Carcinoma Extrahepatic Metastasis in Relation to Tumor Size and Alkaline Phosphatase Levels. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is known to metastasize. However, there are few reports on patients with metastasis at the time of HCC diagnosis. AIMS: To evaluate the incidence and characteristics of extrahepatic metastasis patients presenting at baseline with noncurable, advanced HCC. RESULTS: The total HCC cohort was initially dichotomized into 2 subcohorts, with (n = 214) and without (n = 719) extrahepatic metastasis ('metastasis'), and patient baseline characteristics were compared. The main findings for patients with metastasis (22.9% of total cohort) compared with other, nonmetastatic patients were: more advanced tumors, as judged by larger tumor diameters, more tumor multifocality and percent with portal vein thrombosis, higher blood alpha-fetoprotein and des x03B3;-carboxy prothrombin levels and alkaline phosphatase (ALKP), but not bilirubin levels, and a lower incidence of cirrhosis. There was a strong correlation between increases in tumor size and percent of patients with metastasis. A subset of patients with larger tumors was identified with low blood ALKP levels and better survival. Survival in the total metastasis cohort was lower than in the non-metastasis cohort, as expected, but only in patients with smaller tumors. In patients with larger tumors, survival with or without metastasis was similar and poor. CONCLUSIONS: There was a lower incidence of cirrhosis in HCC patients with metastasis, and they had larger and more aggressive primary tumors. Patients with smaller, but not larger, tumors and metastasis had worse prognosis than patients without metastasis. A distinct subset of metastatic patients was identified that had better prognosis and low ALKP levels. PMID- 26866821 TI - Methylammonium Bismuth Iodide as a Lead-Free, Stable Hybrid Organic-Inorganic Solar Absorber. AB - Methylammonium lead halide (MAPbX3 ) perovskites exhibit exceptional carrier transport properties. But their commercial deployment as solar absorbers is currently limited by their intrinsic instability in the presence of humidity and their lead content. Guided by our theoretical predictions, we explored the potential of methylammonium bismuth iodide (MBI) as a solar absorber through detailed materials characterization. We synthesized phase-pure MBI by solution and vapor processing. In contrast to MAPbX3, MBI is air stable, forming a surface layer that does not increase the recombination rate. We found that MBI luminesces at room temperature, with the vapor-processed films exhibiting superior photoluminescence (PL) decay times that are promising for photovoltaic applications. The thermodynamic, electronic, and structural features of MBI that are amenable to these properties are also present in other hybrid ternary bismuth halide compounds. Through MBI, we demonstrate a lead-free and stable alternative to MAPbX3 that has a similar electronic structure and nanosecond lifetimes. PMID- 26866822 TI - Ocular Fluid Analysis in Children Reveals Interleukin-29/Interferon-lambda1 as a Biomarker for Juvenile Idiopathic Arthritis-Associated Uveitis. AB - OBJECTIVE: Childhood uveitis is a vision-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA-associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight-threatening eye disease. METHODS: AqH (n = 73) and paired serum (n = 66) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay. Twenty-one children with JIA-associated uveitis were compared to 15 children with chronic anterior uveitis without arthritis, 29 children with noninfectious idiopathic uveitis, and 8 children with noninflammatory conditions (controls). For visualization of the joint effect of multiple mediators, we used the radial coordinate visualization (Radviz) method. Optimal biomarker level cutoffs were also determined. RESULTS: The levels of interleukin-29 (IL-29)/interferon-lambda1 (IFNlambda1) were decreased (P < 0.001) and the levels of latency-associated peptide and osteoprotegerin were increased (P = 0.002 and P = 0.001, respectively) in samples of AqH, but not serum, from patients with JIA-associated uveitis. Multivariate analysis correcting for disease activity and treatment revealed that intraocular levels of IL-29/IFNlambda1 were specifically decreased in patients with JIA-associated uveitis as compared to those with idiopathic uveitis. Indeed, JIA-associated uveitis patients and idiopathic uveitis patients showed distinct profiles of intraocular soluble mediators. IL-29/IFNlambda1 showed a high area under the curve value (0.954), with 23.5 pg/ml as the optimal cutoff value. CONCLUSION: We identified IL-29/IFNlambda1 as an intraocular biomarker for JIA-associated uveitis, which suggests that aberrant IFNlambda signaling might be important in JIA-associated uveitis and distinct from other forms of childhood uveitis. PMID- 26866824 TI - Does IARS2 Deficiency Cause an Intrinsic Disorder of Bone Development (Skeletal Dysplasia) or Are the Reported Skeletal Changes Secondary to Growth Hormone Deficiency and Neuromuscular Involvement? PMID- 26866825 TI - Parent-offspring behavior of Jambu fruit doves (Ptilinopus jambu). AB - Fruit doves (Ptilinopus) constitute a genus of small to medium-sized, brightly colored arboreal birds, whose diets consist entirely of fruit. Little is known about the behavior of fruit doves because most species inhabit dense forests and are difficult to observe in the wild. This study describes the parental behavior of Jambu fruit dove pairs (Ptilinopus jambu) in a captive breeding program at the Saint Louis Zoo. Continuous video recordings were made of three pairs which raised a total of eight squabs over 2 years; daily rates of parental and squab behaviors were quantified. Overall, females were present at the nest, brooded their squabs, pecked, and attempted feedings more often than males. Parents also cared for their squabs at different times throughout the day. Males fed and brooded squabs during the middle of the day, while females fed throughout the day and brooded in the morning, evening, and overnight. Feeding rates were lower than those described for seed-eating doves (Columbinae), with hours between consecutive feedings, and squabs rarely begged before feeding events. Most squab behaviors involved initiating or terminating brooding and self-preening. These behaviors increased as squabs approached fledging, and coincided with a shift from full to partial brooding, and a decrease in parental allopreening. Older squabs also initiated feeding less frequently. Together, these data provide the first description of parental behavior in a Ptilinopus fruit dove. The results of this study may help improve captive breeding efforts, which are likely to become increasingly important for future conservation and reintroduction programs. PMID- 26866826 TI - A new perspective on universal preconception care in China. AB - Many risk factors associated with adverse pregnancy outcomes can be identified and modified preconceptionally. Despite a broad consensus that preconception care should be provided to all couples of reproductive age, it has not been integrated in routine healthcare. There are several barriers to its implementation, and even in the most resourceful countries, it is only provided to some select high-risk groups, rather than being an organized healthcare service provision to all. Recently, China seems to be leading the way by implementing preconception care nationwide in all rural areas. Its National Free Preconception Health Examination Project is a unique model of comprehensive preconception care. Advantages of this ambitious project are now becoming evident and benefiting the most vulnerable sections of Chinese society. This commentary provides an overview of National Free Preconception Health Examination Project and highlights the concepts that could be further developed and adapted into a model of preconception care. PMID- 26866827 TI - Increasing Public Health Burden of Arthritis and Other Rheumatic Conditions and Comorbidity: Results From a Statewide Health Surveillance System, 2007-2012. AB - OBJECTIVE: To describe the burden and changing trends of arthritis and other rheumatic conditions (AORCs) on health care and public health by estimating annual rates of emergency department (ED) visits, hospitalizations, and mortality, in addition to medical charges related to AORCs and their comorbidities in Nebraska from 2007 to 2012. METHODS: Nebraska state ED discharge, hospital discharge, and death certificate data from 2007 to 2012 were used to estimate disease burden. AORCs were defined using the standard International Classification of Diseases specified by the National Arthritis Data Workgroup. AORC conditions were defined by the presence of a diagnostic code anywhere on the corresponding record. To identify potential disparities in AORC burden, health care utilization was examined separately across 4 urban/rural categories. RESULTS: Rates of annual ED visits (34% increase), hospitalizations (22% increase) and mean charges (an approximate 30% to 70% increase) from visits involving AORCs increased significantly from 2007 to 2012. Annual rates of ED visits and hospitalizations involving AORCs were lower in urban metropolitan areas compared to other urban/rural designations. AORC-related mortality was highest in small rural communities. Disease profiles revealed that ED visits and hospitalizations involving gout and other crystal arthropathies increased disproportionately compared to other AORCs. CONCLUSION: The public health burden of AORCs increased significantly over the 6-year period studied, posing a growing challenge for patients, families, and the public health system, and AORCs appear to disproportionately impact nonmetropolitan and other rural communities. PMID- 26866828 TI - Facial Scars following Toxic Epidermal Necrolysis: Role of Adnexal Involvement? AB - Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction leading to extensive sloughing of the skin. Late cutaneous complications such as pigmentation disorders are frequently reported. In this report, we present particular facial cutaneous sequelae with histological analysis after TEN. Two young patients who had survived TEN presented permanent multiple hypopigmented papules on the face affecting their quality of life. Histological analysis revealed areas of scarring, dystrophic microcalcifications and sebaceous hyperplasia. Late cutaneous sequelae are well documented; however, the physiopathological mechanisms leading to different clinical presentations remain unknown. We suggest that the destruction of the hair follicle by necrolysis leads to secondary dermal microcalcifications, scarring and sebaceous hyperplasia. Further studies are needed for a better understanding of these findings. PMID- 26866829 TI - Observations from national Italian fixed radiofrequency monitoring network. AB - We analyzed a database of more than 50 million data points from the national Italian fixed radiofrequency (RF) field monitoring network that was operational between June 2002 and November 2006. We applied a modified Regression on Order Statistics approach to reanalyze the database and to deal with the large proportion of entries (39.8%) below detection sensitivity of the probe systems. We found no more than an 18% variation in annual wideband levels during the 2002 2006 period. Mean value for mobile communications band was 0.047 MUW/cm(2) for the period 2005-2006. Findings of this analysis are consistent with similar previous studies and we conclude that mean environmental RF levels from cellular mobile communications systems are typically less than 0.1 MUW/cm(2) . PMID- 26866830 TI - Novel myopathy in a newborn with Shwachman-Diamond syndrome and review of neonatal presentation. AB - Shwachman-Diamond-Bodian syndrome (SDS) is a pleiotropic disorder in which the main features are bone marrow dysfunction and pancreatic insufficiency. Skeletal changes can occur, and in rare cases manifest as severe congenital thoracic dystrophy. We report a newborn boy with asphyxia, narrow thorax, and severe hypotonia initially suggesting a neuromuscular disease. The muscle biopsy showed myopathic changes with prominent variability in muscle fiber size and abnormal expression of developmental isoforms of myosin. The myofibrils showed focal loss and disorganization of myofilaments, and thickening of the Z-discs including some abortive nemaline rods. The boy became permanently dependent on assisted ventilation. Pancreatic insufficiency was subsequently diagnosed, explaining the malabsorption and failure to thrive. Except transitory thrombocytopenia and leukopenia, no major hematological abnormalities were noted. He had bilateral nephrocalcinosis with preserved renal function. Transitory liver dysfunction with elevated transaminase levels and parenchymal changes on ultrasound were registered. The clinical diagnosis was confirmed by detection of compound heterozygous mutations in SBDS using whole-exome sequencing: a recurrent intronic mutation causing aberrant splicing (c.258+2T>C) and a novel missense variant in a highly conserved codon (c.41A>G, p.Asn14Ser), considered to be damaging for the protein structure by in silico prediction programs. The carrier status of the parents has been confirmed. This case illustrates the challenges in differential diagnosis of pronounced neonatal hypotonia with asphyxia and highlights the muscular involvement in SDS. To our knowledge, this is the first report of myopathy evidenced in a patient with clinically and molecularly confirmed SDS. PMID- 26866833 TI - Searching for Classical Brown Fat in Humans: Development of a Novel Human Fetal Brown Stem Cell Model. AB - The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited extension in adult humans of brown depots, which are dramatically reduced after birth, solid cell models to study human brown adipogenesis and its regulatory factors in pathophysiology are urgently needed. Here, we generated a novel human model of brown adipose stem cells, hfB-ASC, derived for the first time from fetal interscapular brown fat depots. Besides the characterization of their stem and classical brown adipose properties, we demonstrated that these cells retain a specific intrinsic differentiation program to functional brown adipocytes, even spontaneously generating organoid structures with brown features. Moreover, for the first time, we investigated the thermogenic and electrophysiological activity of the in vitro-derived fetal brown adipocytes compared to their undifferentiated precursors hfB-ASC, in basal and norepinephrine-induced conditions. In conclusion, from interscapular brown fat of the human fetus we developed and functionally characterized a novel physiological brown adipose stem cell model early programmed to brown differentiation, which may represent a unique opportunity for further studies on brown adipogenesis processes in humans as well as the most suitable target to study novel therapeutic approaches for stimulating brown activity in metabolic pathologies. Stem Cells 2016;34:1679-1691. PMID- 26866834 TI - Corrigendum to "Zinc finger MYND-type containing 8 promotes tumour angiogenesis via induction of vascular endothelial growth factor-A expression" [FEBS Lett. 588 (2014) 3409-3416]. PMID- 26866831 TI - Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients: Results From Studies of the Etiology of Rheumatoid Arthritis. AB - OBJECTIVE: To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first-degree relatives (FDRs) of RA patients. METHODS: We evaluated RA risk factors and inflammatory joint signs in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included 5 HLA-DRB1 shared epitope alleles and 45 RA-associated single-nucleotide polymorphisms; loci were combined using genetic risk scores weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA-related autoantibodies were assessed at baseline. Physical examination was performed at baseline and 2-year follow-up, by observers who were blinded with regard to autoantibody status, to assess inflammatory joint signs as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with inflammatory joint signs. RESULTS: We analyzed 966 non-Hispanic white FDRs at baseline and 262 at 2-year follow-up after excluding those with inflammatory joint signs at baseline. The mean +/- SD age was 47.2 +/- 15.5 years, 71% were female, and 55% were shared epitope positive. Smoking >10 pack-years was associated with inflammatory joint signs at baseline (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26-2.82]) and at 2 years (OR 2.66 [95% CI 1.01-7.03]), compared to never smokers. There was a significant interaction between smoking and age with regard to risk of inflammatory joint signs (P = 0.02). FDRs younger than 50 years with >10 pack-years had the highest risk of inflammatory joint signs (OR 4.39 [95% CI 2.22-8.66], compared to never smokers younger than 50 years). CONCLUSION: In a high-risk cohort of FDRs, smoking and age were associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Further prospective investigations of the factors affecting the transitions between preclinical RA phases are warranted. PMID- 26866836 TI - Single mothers by choice: Mother-child relationships and children's psychological adjustment. AB - Fifty-one solo mother families were compared with 52 two-parent families all with a 4-9-year-old child conceived by donor insemination. Standardized interview, observational and questionnaire measures of maternal wellbeing, mother-child relationships and child adjustment were administered to mothers, children and teachers. There were no differences in parenting quality between family types apart from lower mother-child conflict in solo mother families. Neither were there differences in child adjustment. Perceived financial difficulties, child's gender, and parenting stress were associated with children's adjustment problems in both family types. The findings suggest that solo motherhood, in itself, does not result in psychological problems for children. (PsycINFO Database Record PMID- 26866837 TI - Marital violence and coparenting quality after separation. AB - Research has identified multiple predictors of coparenting quality, but few studies have investigated how intimate partner violence (IPV) affects divorcing couples' coparenting relationships. We addressed this question in a sample of 154 mothers with different marital IPV experiences. Mothers were recruited within 4 months of a divorce filing and completed two interviews 3 months apart. At Time 1, mothers reported on violence and coercive control during marriage, and postseparation behavioral (e.g., parental communication), emotional (e.g., anger), and intrusion (e.g., harassment) dynamics; at Time 2, they reported on coparenting quality (i.e., levels of support and conflict). In the overall sample, divorce and violence variables independently predicted coparenting quality. Mothers were then classified into three groups: no violence (NV; n = 74), situational couple violence (SCV; n = 46), or coercive controlling violence (CCV; n = 34). Of the 3, coparenting quality was lowest in the CCV group. While the SCV group was similar to the NV group on most divorce-related variables, the CCV group reported more hostility at separation and placed less importance on father-child relationships. Finally, patterns of association between study variables and coparenting quality showed some parallels between the SCV and NV groups. For CCV, postseparation harassment and fear were negatively associated with coparenting quality. Findings contribute to understanding predictors of coparenting quality and support the need for individualized assessments of divorce cases with attention to IPV dynamics. PMID- 26866838 TI - Child adjustment and parent functioning: Considering the role of child-driven effects. AB - Based on 13,694 mother-child dyads from the Early Childhood Longitudinal Kindergarten Study (ECLS-K; Rock & Pollack, 2002; Tourangeau, Nord, Le, Sorongon, & Najarian, 2009), this study is an examination of the bidirectional relations between parental and child functioning from kindergarten through 3rd grade. Results from the cross-lagged models demonstrated that child-driven effects co occurred with parental effects, and that these effects were comparable in size. At the same time, however, results from the latent profile analysis (LPA) revealed idiosyncratic patterns of parent and child functioning. Compared with children in the least optimal functioning profiles, those in the average and above-average profiles elicited greater improvement in parents' functioning over time. Although children characterized by poor academic performance at kindergarten appeared to precede parents characterized by harsh parenting at 3rd grade, there was a threshold in the evolving strength of the overall child-driven effects. Taken together, the results from this study underscore the importance of considering reciprocal processes in the parent-child dynamic while also underscoring individual differences in these processes across the early- to middle-childhood years. PMID- 26866839 TI - Corporal punishment and externalizing behaviors in toddlers: The moderating role of positive and harsh parenting. AB - This study investigated whether corporal punishment when the child was 2 years old predicted child externalizing behaviors a year later, and whether or not this association was moderated by parents' observed behavior toward their child. Data came from 218 couples and their firstborn child. The frequency of fathers' corporal punishment when the child was 2 years old predicted child externalizing behaviors a year later, while controlling for initial levels of child externalizing behaviors. Also, observed positive and harsh parenting moderated the relationship between corporal punishment and child externalizing behaviors. These results highlight the importance of continuing to examine the effects of a commonly used form of discipline (i.e., corporal punishment) and the parental climate in which it is used. (PsycINFO Database Record PMID- 26866840 TI - Update: Interim Guidelines for Health Care Providers Caring for Pregnant Women and Women of Reproductive Age with Possible Zika Virus Exposure - United States, 2016. AB - CDC has updated its interim guidelines for U.S. health care providers caring for pregnant women during a Zika virus outbreak (1). Updated guidelines include a new recommendation to offer serologic testing to asymptomatic pregnant women (women who do not report clinical illness consistent with Zika virus disease) who have traveled to areas with ongoing Zika virus transmission. Testing can be offered 2 12 weeks after pregnant women return from travel. This update also expands guidance to women who reside in areas with ongoing Zika virus transmission, and includes recommendations for screening, testing, and management of pregnant women and recommendations for counseling women of reproductive age (15-44 years). Pregnant women who reside in areas with ongoing Zika virus transmission have an ongoing risk for infection throughout their pregnancy. For pregnant women with clinical illness consistent with Zika virus disease,* testing is recommended during the first week of illness. For asymptomatic pregnant women residing in areas with ongoing Zika virus transmission, testing is recommended at the initiation of prenatal care with follow-up testing mid-second trimester. Local health officials should determine when to implement testing of asymptomatic pregnant women based on information about levels of Zika virus transmission and laboratory capacity. Health care providers should discuss reproductive life plans, including pregnancy intention and timing, with women of reproductive age in the context of the potential risks associated with Zika virus infection. PMID- 26866841 TI - Prenatal surgery for myelomeningocele. AB - PURPOSE OF REVIEW: This review summarizes outcomes of fetal surgery for myelomeningocele (MMC) as they compare to postnatal MMC repair and provides insights into areas of investigation to improve fetal MMC repair. RECENT FINDINGS: Recent studies confirm the findings of the Management of Myelomeningocele Study and support the decreased need for postnatal ventricular shunts, improved hindbrain herniation, and improved neurofunctional outcome following open fetal repair compared to postnatal repair at the risk of increased maternal complications and preterm birth. Larger studies of minimally invasive fetal repair demonstrate that, although technically feasible, this approach is associated with longer operative times, increased membrane complications, an earlier gestational age at birth, persistent cerebrospinal fluid leakage, and incidences of persistent postnatal hindbrain herniation resulting in death or requiring surgical decompression. SUMMARY: Open prenatal MMC repair is a new standard of care option with improved postnatal outcomes in a highly specific patient population when performed at select multidisciplinary fetal surgery centers. More investigations are required to optimize minimally invasive approaches prior to reliable clinical application. PMID- 26866842 TI - Noninvasive prenatal testing beyond genomic analysis: what the future holds. AB - PURPOSE OF REVIEW: The discovery of cell-free fetal DNA in maternal blood enabled the development of DNA-based noninvasive prenatal testing. Noninvasive prenatal testing for chromosomal aneuploidy detection was first applied for clinical use a few years ago, resulting in a paradigm shift in prenatal testing. Apart from the use of cell-free fetal nucleic acids for the detection of fetal genetic or chromosomal diseases, we predict that the analysis of cell-free placental RNA and DNA methylation signatures would allow the noninvasive monitoring of placental function. These developments would potentially allow the screening and identification of a range of pregnancy-associated diseases, providing a holistic approach to prenatal management. RECENT FINDINGS: This article covers the advancement of techniques in measuring cell-free fetal RNA and fetal-specific methylation patterns in maternal blood. Recently, genome-wide fetal transcriptome and methylome can be obtained from maternal plasma, which allow the identification of novel biomarkers and the elucidation of the pathogenesis of maternal and fetal diseases. In fact, some studies demonstrated the feasibility of applying the RNA and DNA methylation analysis techniques for prenatal disease assessment. SUMMARY: This study reviews the evidence that demonstrates the potential utilities of cell-free fetal transcriptomic and methylomic analysis for the future assessment of pregnancy-associated disorders. PMID- 26866843 TI - Stakeholder attitudes and needs regarding cell-free fetal DNA testing. AB - PURPOSE OF REVIEW: To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling. RECENT FINDINGS: Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapidly. It is essential that stakeholder views are considered in order to identify and address any ethical and social issues. We provide an overview of stakeholder viewpoints and then focus on the key issues of informed decision making, test uptake, service delivery and information sources. SUMMARY: Stakeholders are positive about the introduction of cell-free fetal DNA testing into clinical practice. They describe both practical and psychological benefits arising from tests that are safe and can potentially be performed earlier in pregnancy. Key concerns, which include the potential for these tests to have a negative impact on informed decision making and increased societal pressure to have testing, can be addressed through careful parent-directed counseling. As applications for these tests expand it is increasingly important to develop innovative approaches to facilitate good understanding for parents who are offered noninvasive prenatal testing. PMID- 26866844 TI - Fetomaternal hemorrhage complicated pregnancy: risks, identification, and management. AB - PURPOSE OF REVIEW: This article aims not only to review recent literature about the clinical features of massive fetomaternal hemorrhage (FMH) and identification of risk factors, but also to alert obstetricians and pediatricians to this underdiagnosed and underestimated severe obstetrical issue. In addition, a simplified flow chart for the antenatal management of suspected FMH is proposed. RECENT FINDINGS: Improvements in obstetrical and neonatal care have decreased perinatal morbidity and mortality and the rate of stillbirth. Unfortunately, because of the nonspecific signs on presentation, adverse outcome associated with massive FMH has not followed this trend and still has devastating consequences. As even the definition varies among publications and there is lack of universal screening, the real nature still remains obscure. Improvements in the diagnosis of fetal anemia, laboratory and intrauterine transfusion techniques, and the implementation of prenatal and postnatal neuroprotection give some hope for the better outcome in the most severe cases. Unfortunately, obstetricians' awareness of the massive FMH remains still at an unacceptably low level. SUMMARY: There is an urgent need for the internationally accepted definition, standardized pregnancy management protocol, and structured follow-up of neonates from such pregnancies. We suggest the international registry of massive FMH cases. PMID- 26866845 TI - Autophagy is involved in the pathogenesis of experimental autoimmune neuritis in rats. AB - Recent studies have shown that autophagy is involved in peripheral nervous system disease. However, the role of autophagy in the pathogenesis of experimental autoimmune neuritis (EAN) remains unclear. Therefore, EAN was induced by a subcutaneous injection into both hind footpads of synthetic neuritogenic P2(57 81) peptide in male Lewis rats. The clinical evaluation was completed using a 10 point scale method. The histological alteration of sciatic nerves was analyzed by hematoxylin and eosin and luxol fast blue staining. The ultrastructure of sciatic nerves was analyzed by transmission electron microscopy. Expressions of beclin-1 and microtubule-associated protein light chain-3 (LC3) and p62/SQSTM1 were determined by western blot. 3-Methyladenine, the inhibitor of autophagy, was used in this research. Results showed that the clinical scores were significantly increased from day 6 to day 16 after immunization compared with the control group. Compared with the control group, the number of inflammatory cells and the histological score of sciatic nerves were significantly increased, expressions of beclin-1 and LC3-II and the ratio of LC3-II/LC3-I in the sciatic nerve were significantly increased, and the expression of p62 was significantly decreased in the EAN model group. Considerable double-membrane autophagosomes in axons and myelin sheaths of sciatic nerves were observed and the number of autophagosomes in axons and myelin sheaths of sciatic nerves in the EAN model group was obviously increased compared with the control group. 3-Methyladenine ameliorated the neurologic severity of EAN. Our results suggest that autophagy activity in nerve tissue of EAN rats is increased, which may be associated with the pathogenesis of EAN. PMID- 26866846 TI - Determination of the Prevalence, Height, and Location of the Maxillary Sinus Septa Using Cone Beam Computed Tomography. AB - INTRODUCTION: Presence of the maxillary sinus septum would increase the risk of sinus membrane perforation during sinus floor elevation surgery. Three dimensional radiographic techniques are recommended for the evaluation of the maxillary sinuses. MATERIALS AND METHODS: This cross-sectional study evaluated 946 maxillary sinuses using the cone beam computed tomography. Presence of septa, number, location, height, and orientation were evaluated and recorded in data forms. RESULTS: Of all patients, 44.8% had at least 1 septum; 36.8% had 1 septum in their right maxillary sinus, 27.4% in their left, and 35.8% in both sides. No statistically significant difference was found between males and females or the right and left maxillary sinuses in terms of the prevalence of septa. In 35.1% of patients, the septum was in the middle of the sinus. Mediolateral septa had the highest frequency (59.2%). The highest mean septum height in the medial zone was 6.3 +/- 3.1 mm in the right sinus and 7.1 +/- 3.1 mm in the left sinus. CONCLUSION: Approximately 45% of patients had at least 1 septum, and this finding emphasizes the need for the assessment of the maxillary sinuses to prevent complications. PMID- 26866847 TI - Subantral Augmentation With Mineralized Cortical Bone Allograft Material: Clinical, Histological, and Histomorphometric Analyses and Graft Volume Assessments. AB - PURPOSE: The aim of this study was to clinically and histologically evaluate the effect of using mineralized cortical bone allograft in sinus lift augmentation and to 3-dimensionally quantify volumetric changes in maxillary sinuses augmented over a 2-year period. MATERIALS AND METHODS: Eleven patients affected with less than 3 mm of residual ridge were enrolled in the study. After sinus grafting with a mineralized bone allograft, the site was covered with a collagen wound dressing. During implant placement 4 months later, a biopsy was obtained for histological and histomorphometry evaluations. Bone volume changes were also evaluated. RESULTS: Biopsies showed mature cancellous bone with a predominantly lamellar structure. The well-vascularized intertrabecular spaces were filled with connective tissue and bone marrow. Histomorphometry evaluations revealed a mean 43.76 +/- 1.47% of bone marrow, 40.16 +/- 1.35% of mineralized bone and 16.59 +/- 0.55% of woven bone. The mean of residual particles was 0.47 +/- 0.01%. Volumetric measurements showed a mean volume of grafted material 16.24 +/- 1.55 cm at T0, 14.48 +/- 1.48 cm at T1, and 13.06 +/- 1.39 cm at T2. The mean volume retraction was 10.83% of the initial total volume at (T0-T1) and 9.8% at (T1-T2). CONCLUSIONS: The clinical and histological results indicated that mineralized cortical bone allograft promoted de novo bone formation and can be used for sinus lift procedure. PMID- 26866848 TI - Diffusion-Tensor Imaging of Thigh Muscles in Duchenne Muscular Dystrophy: Correlation of Apparent Diffusion Coefficient and Fractional Anisotropy Values With Fatty Infiltration. AB - OBJECTIVE: The purpose of this study is to investigate the correlation of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with fatty infiltration in the thigh muscles of patients with Duchenne muscular dystrophy (DMD) using diffusion-tensor imaging (DTI). SUBJECTS AND METHODS: Twenty-one boys with DMD were recruited. The grade of fatty infiltration and the ADC and FA values of four thigh muscles (rectus femoris, semitendinosus, sartorius, and gracilis) were measured, and the FA and ADC values were compared with the grade of fatty infiltration. Twenty age-matched healthy boys were enrolled as the control group. The differences in the ADC and FA values of the thigh muscles between patients with DMD and the control group were compared. RESULTS: The patients with DMD showed lower FA values and higher ADC values in all measured muscles when compared with the control group. The FA and ADC values were correlated with the grade of fatty infiltration. For the rectus femoris muscle, r = -0.753 and p = 0.007 for FA, and r = 0.685 and p = 0.001 for ADC. For the semitendinosus muscle, r = -0.621 and p = 0.041 for FA, and r = 0.705 and p = 0.021 for ADC. For the sartorius muscle, r = -0.662 and p = 0.027 for FA, and r = 0.701 and p = 0.017 for ADC. For the gracilis muscle, r = -0.618 and p = 0.043 for FA, and r = 0.695 and p = 0.022 for ADC. CONCLUSION: Damage to the thigh muscles in patients with DMD can be detected by ADC and FA values using DTI. DTI can be used to assess the severity of the disease. PMID- 26866849 TI - Effect of Therapeutic Hypothermia on Survival and Neurologic Outcome in the Elderly. AB - Old age is considered a negative prognostic factor after out-of-hospital cardiac arrest (OHCA). The purpose of this study was to assess the benefit of therapeutic hypothermia (TH) on survival and neurologic outcome in the elderly. This is a retrospective study of patients treated for OHCA from April 2011 to August 2013 in a regional cardiac system. Patients with return of spontaneous circulation (ROSC) are directed to designated cardiac receiving centers with established TH protocols. The decision to initiate TH is determined by the treating physician. All patients 65 years or older were identified. Patients were excluded if awake and responsive in the emergency department, died before hospital admission, or had preexisting coma. The adjusted odds ratio for survival with good neurologic outcome (defined as cerebral performance category [CPC] 1 or 2) was calculated for patients who received TH compared to a reference group without TH. There were 1612 patients, of whom 552 (34%) received TH. Median age was 78 (inter-quartile range [IQR] 71-85); 56% was male. 493 (31%) patients survived to hospital discharge, 266 (17%) with CPC of 1 or 2. Of 1292 patients considered for TH, 192 (25%) of 552 patients who received TH survived to hospital discharge and 97 (18%) with good neurologic outcome compared to 150 (20%) and 57 (8%), respectively, without TH. The adjusted odds ratio for survival with good neurologic outcome for TH was 2.0 (95% CI 1.3-3.3). TH is associated with improved neurologic outcome in the elderly population. PMID- 26866853 TI - A Case-control Study of Diphtheria in the High Incidence City of Hyderabad, India. AB - BACKGROUND: India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. METHODS: We performed a 1:1 case-control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls RESULTS: : There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58-8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18-13.45) remained significantly associated with diphtheria on multivariate analysis. CONCLUSION: To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered. PMID- 26866854 TI - Paenibacillus alvei Sepsis in a Neonate. PMID- 26866855 TI - Pediatric Human Granulocytic Anaplasmosis is Rare in Europe. PMID- 26866856 TI - Serial Changes of Serum Cytokine in a Pediatric Patient with Severe Fever with Thrombocytopenia Syndrome. PMID- 26866857 TI - Denouement. PMID- 26866858 TI - Vapor Condensed and Supercooled Glassy Nanoclusters. AB - We use molecular simulation to study the structural and dynamic properties of glassy nanoclusters formed both through the direct condensation of the vapor below the glass transition temperature, without the presence of a substrate, and via the slow supercooling of unsupported liquid nanodroplets. An analysis of local structure using Voronoi polyhedra shows that the energetic stability of the clusters is characterized by a large, increasing fraction of bicapped square antiprism motifs. We also show that nanoclusters with similar inherent structure energies are structurally similar, independent of their history, which suggests the supercooled clusters access the same low energy regions of the potential energy landscape as the vapor condensed clusters despite their different methods of formation. By measuring the intermediate scattering function at different radii from the cluster center, we find that the relaxation dynamics of the clusters are inhomogeneous, with the core becoming glassy above the glass transition temperature while the surface remains mobile at low temperatures. This helps the clusters sample the highly stable, low energy structures on the potential energy surface. Our work suggests the nanocluster systems are structurally more stable than the ultrastable glassy thin films, formed through vapor deposition onto a cold substrate, but the nanoclusters do not exhibit the superheating effects characteristic of the ultrastable glass states. PMID- 26866859 TI - The effects of combined sewer overflow events on riverine sources of drinking water. AB - This study was set out to investigate the impacts of Combined Sewer Overflows (CSOs) on the microbiological water quality of a river used as a source of drinking water treatment plants. Escherichia coli concentrations were monitored at various stations of a river segment located in the Greater Montreal Area including two Drinking Water Intakes (DWIs) in different weather conditions (dry weather and wet weather (precipitation and snowmelt period)). Long-term monitoring data (2002-2011) at DWIs revealed good microbiological water quality with E. coli median concentrations of 20 and 30 CFU/100 mL for DWI-1 and DWI-2 respectively. However, E. coli concentration peaks reached up to 510 and 1000 CFU/100 mL for both DWIs respectively. Statistical Process Control (SPC) analysis allowed the identification of E. coli concentration peaks in almost a decade of routine monitoring data at DWIs. Almost 80% of these concentrations were linked to CSO discharges caused by precipitation exceeding 10 mm or spring snowmelt. Dry weather monitoring confirmed good microbiological water quality. Wet weather monitoring showed an increase of approximately 1.5 log of E. coli concentrations at DWIs. Cumulative impacts of CSO discharges were quantified at the river center with an increase of approximately 0.5 log of E. coli concentrations. Caffeine (CAF) was tested as a potential chemical indicator of CSO discharges in the river and CAF concentrations fell within the range of previous measurements performed for surface waters in the same area (~20 ng/L). However, no significant differences were observed between CAF concentrations in dry and wet weather, as the dilution potential of the river was too high. CSO event based monitoring demonstrated that current bi-monthly or weekly compliance monitoring at DWIs underestimate E. coli concentrations entering DWIs and thus, should not be used to quantify the risk at DWIs. High frequency event-based monitoring is a desirable approach to establish the importance and duration of E. coli peak concentrations entering DWIs. PMID- 26866860 TI - The FDA Pivots Toward Patient-Centeredness: Patient Engagement Advisory Committee. PMID- 26866861 TI - Ankle Brachial Index and Foot Ulcer Etiology. PMID- 26866866 TI - Pieces of the HOPD Payment Puzzle: NCCI Edits, OPPS Payment Status Indicators, and LCDs. PMID- 26866867 TI - Negative-Pressure Therapy to Reduce the Risk of Wound Infection Following Diverting Loop Ileostomy Reversal: An Initial Study. AB - OBJECTIVE: To evaluate if the application of a negative-pressure therapy system (Prevena Incision Management System, Kinetics Concepts Inc, [KCI] an Acelity Company, San Antonio, Texas) on ileostomy-closure surgical wounds would reduce surgical site infections (SSIs) in comparison with conventional closure and dressing. DESIGN: Prospective interventional pilot study. SETTING: La Paz University Hospital, tertiary care academic hospital in Madrid, Spain. PATIENTS: The Prevena device was applied on the wounds of 17 consecutive patients undergoing ileostomy reversal. Control subjects were 43 patients undergoing the same procedure, in which conventional dressings were used for the wound. INTERVENTION: The device was applied on the wound immediately after surgery (under sterile conditions) and maintained for 5 to 7 days. Patients were evaluated daily, and on the seventh postoperative day, the device was removed and wounds carefully inspected. Another evaluation was performed a month after the surgical intervention in the outpatient clinic. MAIN OUTCOME MEASURE: The primary end point of the study was the detection of SSI (defined according to the Centers for Disease Control and Prevention definitions). Other intervention-related complications were also registered. MAIN RESULTS: There were no significant differences in demographic variables between groups. In the control group, 9 patients (21%) presented SSI, with statistical significance (P < .038) when compared with the intervention group (0%). There were no complications associated with the application of the Prevena device. Other complications (for example, ileus or obstruction) occurred in 30% of patients. CONCLUSIONS: The negative pressure Prevena System was safe and easy to use and may prevent SSIs in dirty wounds, such as those from ileostomy closure. PMID- 26866868 TI - Tissue-Engineered Skin Substitute Enhances Wound Healing after Radiation Therapy. AB - OBJECTIVE: When given in conjunction with surgery for treating cancer, radiation therapy may result in impaired wound healing, which, in turn, could cause skin ulcers. In this study, bilayer and monolayer autologous skin substitutes were used to treat an irradiated wound. MATERIALS AND METHODS: A single dose of 30 Gy of linear electron beam radiation was applied to the hind limb of nude mice before creating the skin lesion (area of 78.6 mm). Monolayer tissue-engineered skin substitutes (MTESSs) were prepared by entrapping cultured keratinocytes in fibrin matrix, and bilayer tissue-engineered skin substitutes (BTESSs) were prepared by entrapping keratinocytes and fibroblasts in separate layers. Bilayer tissue-engineered skin substitute and MTESS were implanted to the wound area. Gross appearance and wound area were analyzed to evaluate wound healing efficiency. Skin regeneration and morphological appearance were observed via histological and electron microscopy. Protein expressions of transforming growth factor beta1 (TGF-beta1), platelet-derived growth factor BB (PDGF-BB), and vascular endothelial growth factor (VEGF) in skin regeneration were evaluated by immunohistochemistry (IHC). RESULTS: Macroscopic observation revealed that at day 13, treatments with BTESS completely healed the irradiated wound, whereas wound sizes of 1.1 +/- 0.05 and 6.8 +/- 0.14 mm were measured in the MTESS-treated and untreated control groups, respectively. Hematoxylin-eosin (H&E) analysis showed formation of compact and organized epidermal and dermal layers in the BTESS treated group, as compared with MTESS-treated and untreated control groups. Ultrastructural analysis indicates maturation of skin in BTESS-treated wound evidenced by formation of intermediate filament bundles in the dermal layer and low intercellular space in the epidermal layer. Expressions of TGF-beta1, PDGF BB, and VEGF were also higher in BTESS-treated wounds, compared with MTESS treated wounds. CONCLUSIONS: These results indicate that BTESS is the preferred treatment for irradiated wound ulcers. PMID- 26866869 TI - Assessment of Chicken-Egg Membrane as a Dressing for Wound Healing. AB - OBJECTIVES: To examine the efficacy of the folk remedy of chicken-egg membrane dressing on wound healing. DESIGN: Full-thickness excisional wounds were created on 14 male Sprague-Dawley rats in 2 separate trials. Each animal received 2 wounds on the upper back. One wound was untreated, and the other was dressed with chicken-egg membrane to assess its impact on wound healing. Half of the rats received egg membrane treatment on the inferior wound, whereas the other half received egg membrane treatment on the superior wound. Membrane replacement, wound debridement, and imaging were done on days 5, 8, and 10 and then imaging continued on days 12, 14, 16, 18, and 20 of the experiment. Healing rate was measured based on the wound area over the 20 days of the experiment. RESULTS: The wounds dressed with chicken-egg membrane had a significantly (P < .01) faster rate of healing compared with the control at the early stages of healing between days 0 and 5. This group healed 21% faster during this early phase, compared with the control group. Overall, however, wound healing rates were indistinguishable from days 5 to 20. CONCLUSION: Chicken-egg membrane dressing significantly improves healing of cutaneous wounds in the early stages of wound healing. PMID- 26866870 TI - Development of a Nutrition Screening Tool for an Outpatient Wound Center. AB - OBJECTIVE: To construct a quickly and easily administered nutrition screening tool using variables believed to be predictive of malnutrition risk in the wound patient population. DESIGN: A prospective pilot study assessed patients on a list of suspected variables, as well as the Scored Patient-Generated Subjective Global Assessment (PG-SGA), chosen as the criterion standard. Variables were analyzed to select the most appropriate items for inclusion on a new nutrition screening tool using preliminary bivariate correlations and chi tests of association. Items significantly associated with malnutrition were dichotomized, and binary logistic regression analyses were performed to arrive at a final model. A sum score was computed, and receiver operating characteristic analysis was used to determine designation of risk. SETTING: An outpatient wound center in Northeast Ohio. PARTICIPANTS: The pilot study included a convenience sample of 105 outpatients with at least 1 active wound. MAIN OUTCOME MEASURES: Malnutrition as assessed by the Scored PG-SGA. MAIN RESULTS: The final nutrition screening tool, the MEAL Scale, is composed of 4 dichotomous elements: multiple wounds (number of wounds), eats less than 3 meals per day, appetite decrease (eats less than usual), and level of activity. These variables predicted 83.7% of the malnutrition cases assessed by the Scored PG-SGA. The receiver operating characteristic analysis showed an acceptable area under the curve (0.8581), and a cutoff score of 2 or greater was selected to indicate risk (median sensitivity = 91.4%, median specificity = 60.9%). CONCLUSIONS: Although further studies of validity and reliability are necessary to establish the tool before widespread use, the MEAL Scale is a needed step toward nutrition screening in a wound patient population. PMID- 26866871 TI - The Strategic View of Modified Stage 2 Meaningful Use: Part 3. PMID- 26866873 TI - Comparative study of CXC chemokines modulation in brown trout (Salmo trutta) following infection with a bacterial or viral pathogen. AB - Chemokine modulation in response to pathogens still needs to be fully characterised in fish, in view of the recently described novel chemokines present. This paper reports the first comparative study of CXC chemokine genes transcription in salmonids (brown trout), with a particular focus on the fish specific CXC chemokines (CXCL_F). Adopting new primer sets, optimised to specifically target mRNA, a RT-qPCR gene screening was carried out. Constitutive gene expression was assessed first in six tissues from SPF brown trout. Transcription modulation was next investigated in kidney and spleen during septicaemic infection induced by a RNA virus (Viral Haemorrhagic Septicaemia virus, genotype Ia) or by a Gram negative bacterium (Yersinia ruckeri, ser. O1/biot. 2). From each target organ specific pathogen burden, measured detecting VHSV-glycoprotein or Y. ruckeri 16S rRNA, and IFN-gamma gene expression were analysed for their correlation to chemokine transcription. Both pathogens modulated CXC chemokine gene transcript levels, with marked up-regulation seen in some cases, and with both temporal and tissue specific effects apparent. For example, Y. ruckeri strongly induced chemokine transcription in spleen within 24h, whilst VHS generally induced the largest increases at 3d.p.i. in both tissues. This study gives clues to the role of the novel CXC chemokines, in comparison to the other known CXC chemokines in salmonids. PMID- 26866874 TI - Exploratory study of once-daily transcranial direct current stimulation (tDCS) as a treatment for auditory hallucinations in schizophrenia. AB - BACKGROUND: Auditory hallucinations are resistant to pharmacotherapy in about 25% of adults with schizophrenia. Treatment with noninvasive brain stimulation would provide a welcomed additional tool for the clinical management of auditory hallucinations. A recent study found a significant reduction in auditory hallucinations in people with schizophrenia after five days of twice-daily transcranial direct current stimulation (tDCS) that simultaneously targeted left dorsolateral prefrontal cortex and left temporo-parietal cortex. HYPOTHESIS: We hypothesized that once-daily tDCS with stimulation electrodes over left frontal and temporo-parietal areas reduces auditory hallucinations in patients with schizophrenia. METHODS: We performed a randomized, double-blind, sham-controlled study that evaluated five days of daily tDCS of the same cortical targets in 26 outpatients with schizophrenia and schizoaffective disorder with auditory hallucinations. RESULTS: We found a significant reduction in auditory hallucinations measured by the Auditory Hallucination Rating Scale (F2,50=12.22, P<0.0001) that was not specific to the treatment group (F2,48=0.43, P=0.65). No significant change of overall schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale was observed. CONCLUSIONS: The lack of efficacy of tDCS for treatment of auditory hallucinations and the pronounced response in the sham-treated group in this study contrasts with the previous finding and demonstrates the need for further optimization and evaluation of noninvasive brain stimulation strategies. In particular, higher cumulative doses and higher treatment frequencies of tDCS together with strategies to reduce placebo responses should be investigated. Additionally, consideration of more targeted stimulation to engage specific deficits in temporal organization of brain activity in patients with auditory hallucinations may be warranted. PMID- 26866875 TI - Interstitial stromal progenitors during kidney development: here, there and everywhere. AB - In recent years, the renal interstitium has been identified as the site of multiple cell types, giving rise to multiple contiguous cellular networks with multiple fundamental structural and functional roles. Few studies have been carried out on the morphological and functional properties of the stromal/interstitial renal cells during the intrauterine life. This work was aimed at reviewing the peculiar features of renal interstitial stem/progenitor cells involved in kidney development. The origin of the renal interstitial progenitor cells remains unknown. During kidney development, besides the Six2 + cells of the cap mesenchyme, a self-renewing progenitor population, characterized by the expression of Foxd1, represents the first actor of the non-nephrogenic lineage. Foxd1 + interstitial progenitors originate the cortical and the renal medullary interstitial progenitors. Here, the most important stromal/interstitial compartments present in the developing human kidney will be analyzed: capsular stromal cells, cortical interstitial cells, medullary interstitial cells, the interstitium inside the renal stem cell niche, Hilar interstitial cells and Ureteric interstitial cells. Data reported here indicate that the different interstitial compartments of the developing kidney are formed by different cell types that characterize the different renal areas. Further studies are needed to better characterize the different pools of renal interstitial progenitors and their role in human nephrogenesis. PMID- 26866876 TI - Reliability and Validity of the Therapy Intensity Level Scale: Analysis of Clinimetric Properties of a Novel Approach to Assess Management of Intracranial Pressure in Traumatic Brain Injury. AB - We aimed to assess the reliability and validity of the Therapy Intensity Level scale (TIL) for intracranial pressure (ICP) management. We reviewed the medical records of 31 patients with traumatic brain injury (TBI) in two European intensive care units (ICUs). The ICP TIL was derived over a 4-day period for 4-h (TIL4) and 24-h epochs (TIL24). TIL scores were compared with historical schemes for TIL measurement, with each other, and with clinical variables. TIL24 scores in ICU patients with TBI were compared with two control groups: patients with extracranial trauma necessitating intensive care (Trauma_ICU; n = 20) and patients with TBI not needing ICU care (TBI_WARD; n = 19), to further determine the discriminative validity of the TIL for ICP-related ICU interventions. Interrater and intraobserver agreement were excellent for TIL4 and TIL24 (Cohen kappa: 0.98-0.99; intraclass correlation coefficient: 0.99-1; p < 0.0005). The mean + standard deviation (SD) TIL24 in the ICU TBI cohort was significantly higher than the Trauma_ICU patients and the TBI_WARD patients (8.2 +/- 3.2 vs. 2.2 +/- 0.9 and 0.1 +/- 0.1, respectively; p < 0.005 for both comparisons). Correlations between the TIL scale scores and historical TIL scores, between TIL24 and the Glasgow Coma Scale, and between a range of TIL metrics and summary measures of ICP over the 4-day period, were all highly significant (p < 0.01). The results were consistent with the expected direction. A linear mixed effect analysis, accounting for within-subjects repeated measures, showed strong correlation between TIL4 and 4-h ICP (p < 0.0000005). The TIL scale is a reliable measurement instrument with a high degree of validity for assessing the therapeutic intensity level of ICP management in patients with TBI. PMID- 26866877 TI - One-step synthesis of high-density peptide-conjugated gold nanoparticles with antimicrobial efficacy in a systemic infection model. AB - The increase in antibiotic drug resistance and the low number of new antibacterial drugs approved in the last few decades requires the development of new antimicrobial strategies. Antimicrobial peptides (AMPs) are very promising molecules to fight microbial infection since they kill quickly bacteria and, in some cases, target bacterial membrane. Although some AMPs may be stable against proteolytic degradation by chemical modification, in general, low AMP activity and stability in the presence of serum and proteolytic enzymes as well as their cytotoxicity have impaired their clinical translation. Here, we describe a one step methodology to generate AMP-conjugated gold nanoparticles (Au NPs), with a high concentration of AMPs (CM-SH) (~240 AMPs per NP), controlled size (14 nm) and low polydispersity. AMP-conjugated Au NPs demonstrated higher antimicrobial activity and stability in serum and in the presence of non-physiological concentrations of proteolytic enzymes than soluble AMP, as well as low cytotoxicity against human cells. Moreover, the NPs demonstrated high antimicrobial activity after in vivo administration in a chronic wound and in an animal model of systemic infection. PMID- 26866878 TI - Two-Dimensional Disorder in Black Phosphorus and Monochalcogenide Monolayers. AB - Ridged, orthorhombic two-dimensional atomic crystals with a bulk Pnma structure such as black phosphorus and monochalcogenide monolayers are an exciting and novel material platform for a host of applications. Key to their crystallinity, monolayers of these materials have a 4-fold degenerate structural ground state, and a single energy scale EC (representing the elastic energy required to switch the longer lattice vector along the x- or y-direction) determines how disordered these monolayers are at finite temperature. Disorder arises when nearest neighboring atoms become gently reassigned as the system is thermally excited beyond a critical temperature Tc that is proportional to EC/kB. EC is tunable by chemical composition and it leads to a classification of these materials into two categories: (i) Those for which EC >= kBTm, and (ii) those having kBTm > EC >= 0, where Tm is a given material's melting temperature. Black phosphorus and SiS monolayers belong to category (i): these materials do not display an intermediate order-disorder transition and melt directly. All other monochalcogenide monolayers with EC > 0 belonging to class (ii) will undergo a two-dimensional transition prior to melting. EC/kB is slightly larger than room temperature for GeS and GeSe, and smaller than 300 K for SnS and SnSe monolayers, so that these materials transition near room temperature. The onset of this generic atomistic phenomena is captured by a planar Potts model up to the order-disorder transition. The order-disorder phase transition in two dimensions described here is at the origin of the Cmcm phase being discussed within the context of bulk layered SnSe. PMID- 26866879 TI - Expression of MIF and CD74 in leukemic cell lines: correlation to DR expression destiny. AB - Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein, which apart from its role as a chaperone dedicated to MHCII molecules, is known to be a high affinity receptor for macrophage migration inhibitory factor (MIF). The present study aimed to define the roles of CD74 and MIF in the immune surveillance escape process. Towards this direction, the cell lines HL-60, Raji, K562 and primary pre B leukemic cells were examined for expression and secretion of MIF. Flow cytometry analysis detected high levels of MIF and intracellular/membrane CD74 expression in all leukemic cells tested, while MIF secretion was shown to be inversely proportional to intracellular HLA-DR (DR) expression. In the MHCII negative cells, IFN-gamma increased MIF expression and induced its secretion in HL-60 and K562 cells, respectively. In K562 cells, CD74 (Iip33Iip35) was shown to co-precipitate with HLA-DObeta (DObeta), inhibiting thus MIF or DR binding. Induced expression of DOalpha in K562 (DOalpha-DObeta+) cells in different transfection combinations decreased MIF expression and secretion, while increasing surface DR expression. Thus, MIF could indeed be part of the antigen presentation process. PMID- 26866880 TI - Clinical evaluation of microRNA-145 expression in renal cell carcinoma: a promising molecular marker for discriminating and staging the clear cell histological subtype. AB - The vast majority of malignancies detected in renal parenchyma are diagnosed as renal cell carcinoma (RCC), whose subtype discrimination and determination of prognosis may contribute to the selection of the adequate therapy. Recently, a new class of small non-coding RNAs, known as microRNAs, has proven to be among the most promising biomarkers for providing this information. Herein, we sought to add up to this knowledge by evaluating the expression levels of microRNA-145 (miR-145) in RCC. For that purpose, total RNA from 58 cancerous and 44 adjacent non-cancerous renal tissues was firstly extracted and then polyadenylated and reverse transcribed to cDNA. MiR-145 levels were finally analyzed by developing and applying a highly sensitive real-time PCR protocol, while their clinical significance was determined via comprehensive statistical analysis. Our data showed that miR-145 was significantly downregulated in cancerous samples and could discriminate between clear cell and non-clear cell subtypes. Moreover, miR 145 expression was found to be correlated with primary tumor staging of cancerous samples, something also noticed in the clear cell RCC subset, in which miR-145 levels were negatively correlated with tumor size as well. Overall, these results indicate that miR-145 might constitute a promising molecular marker for RCC classification and staging. PMID- 26866881 TI - An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours. AB - INTRODUCTION: Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize. There is frequent association with females of reproductive age, a history of abdominal surgery or trauma and a family history of fibromatoses. Intra-abdominal DTs are infrequently sporadic and more commonly associated with inherited disorders such as familial adenomatous polyposis (FAP), attenuated FAP and Gardener's syndrome. PRESENTATION OF CASE: The authors report a rare case of small bowel obstruction and perforation secondary to sporadic, synchronous intra abdominal DTs in a 54-year old man with atypical symptoms and no risk factors or family history. DISCUSSION: Intra-abdominal DTs have a worse prognosis as they can cause intestinal bleeding, obstruction and perforation. Due to the rarity of these tumours there are no clear guidelines on their management and this is instead based on small case series from specialist centres. In the non-acute setting patients with sporadic intra-abdominal DTs should be managed in a specialist sarcoma unit by a multidisciplinary team. In the presence of FAP or other polyposis syndromes patients with DTs should be managed at a specialist colorectal unit. Emergent presentations require emergency surgery in suitable candidates. CONCLUSION: In non-emergency presentations of DTs, it is essential to exclude FAP, AFAP and other hereditary polyposis syndromes since this affects treatment and subsequent follow-up. PMID- 26866882 TI - A rare case of lacrimal adenoid cystic carcinoma with large hepatic and multiple pulmonary metastases with successful surgical treatment. AB - INTRODUCTION: Adenoid cystic carcinoma (ACC) of the lacrimal gland is rare but with high recurrence rates and late metastases. They occasionally metastasise via haematogenous spread to lungs, brain and bone. Liver is a rare site of metastasis and is usually present with disseminated disease. PRESENTATION OF CASE: A 42 year old lady, a known case of adenoid cystic carcinoma of the lacrimal gland who had been operated 4 years ago for the same followed by chemotherapy and radiotherapy. She was detected with large hepatic and bilateral multiple pulmonary metastases. A right hepatectomy was done. After six months when her general condition improved we did a staged pulmonary metastatectomy. Histology confirmed the diagnosis. She is presently doing well with no recurrence since 18 months. DISCUSSION: Usually asymptomatic, the commonest symptom is pain. It is a locally invasive disease with a poor prognosis if detected late. Surgery is the only proven therapy. Isolated hepatic metastases being managed surgically has been reported. However, extensive, staged, surgical resection of hepatic and pulmonary metastases has not been reported. CONCLUSION: Lacrimal ACC is an aggressive tumour with known late metastases with the liver being affected seldomly. Our case highlights that even disseminated metastases to the liver and the lungs from lacrimal ACC can be managed surgically with a good outcome. To our knowledge, no such report with distant metastases to the liver and the lung along with their successful surgical management has been reported. PMID- 26866885 TI - The study of electrical conductivity and diffusion behavior of water-based and ferro/ferricyanide-electrolyte-based alumina nanofluids. AB - Nanofluids are liquids containing suspensions of solid nanoparticles and have attracted considerable attention because they undergo substantial mass transfer and have many potential applications in energy technologies. Most studies on nanofluids have used low-ionic-strength solutions, such as water and ethanol. However, very few studies have used high-ionic-strength solutions because the aggregation and sedimentation of nanoparticles cause a stability problem. In this study, a stable water-based alumina nanofluid was prepared using stirred bead milling and exhibits a high electrical conductivity of 2420 MUS/cm at 23 degrees C and excellent stability after five severe freezing-melting cycles. We then developed a process for mixing the water-based nanofluid with a high-ionic strength potassium ferro/ferricyanide electrolyte and sodium dodecyl sulfate by using stirred bead milling and ultrasonication, thus forming a stable electrolyte based nanofluid. According to the rotating disk electrode study, the electrolyte based alumina nanofluid exhibits an unusual increase in the limiting current at high angular velocities, resulting from a combination of local percolation behavior and shear-induced diffusion. The electrolyte-based alumina nanofluid was demonstrated in a possible thermogalvanic application, since it is considered to be an alternative electrolyte for thermal energy harvesters because of the increased electrical conductivity and confined value of thermal conductivity. PMID- 26866884 TI - Photosensitizer-loaded gold nanorods for near infrared photodynamic and photothermal cancer therapy. AB - Despite the advancement of photodynamic therapy and photothermal therapy, the ability to form compact nanocomplex for combined photodynamic and photothermal cancer therapy under a single near infrared irradiation remains limited. In this work, we prepared an integrated sub-100 nm nanosystem for simultaneous near infrared photodynamic and photothermal cancer therapy. The nanosystem was formed by adsorption of silicon 2,3-naphthalocyanine dihydroxide onto gold nanorod followed by covalent stabilization with alkylthiol linked polyethylene glycol. The effects of alkylthiol chain length on drug loading, release and cell killing efficacy were examined using 6-mercaptohexanoic acid, 11-mercaptoundecanoic acid and 16-mercaptohexadecanoic acid. We found that the loading efficiency of silicon 2,3-naphthalocyanine dihydroxide increased and the release rate decreased with the increase of the alkylthiol chain length. We demonstrated that the combined near infrared photodynamic and photothermal therapy using the silicon 2,3 naphthalocyanine dihydroxide-loaded gold nanorods exhibit superior efficacy in cancer cell destruction as compared to photodynamic therapy and photothermal therapy alone. The nanocomplex stabilized with 16-mercaptohexadecanoic acid linked polyethylene glycol provided highest cell killing efficiency as compared to those stabilized with the other two stabilizers under low drug dose. This new nanosystem has potential to completely eradicate tumors via noninvasive phototherapy, preventing tumor reoccurrence and metastasis. PMID- 26866883 TI - Estrogen, SNP-Dependent Chemokine Expression and Selective Estrogen Receptor Modulator Regulation. AB - We previously reported, on the basis of a genome-wide association study for aromatase inhibitor-induced musculoskeletal symptoms, that single-nucleotide polymorphisms (SNPs) near the T-cell leukemia/lymphoma 1A (TCL1A) gene were associated with aromatase inhibitor-induced musculoskeletal pain and with estradiol (E2)-induced TCL1A expression. Furthermore, variation in TCL1A expression influenced the downstream expression of proinflammatory cytokines and cytokine receptors. Specifically, the top hit genome-wide association study SNP, rs11849538, created a functional estrogen response element (ERE) that displayed estrogen receptor (ER) binding and increased E2 induction of TCL1A expression only for the variant SNP genotype. In the present study, we pursued mechanisms underlying the E2-SNP-dependent regulation of TCL1A expression and, in parallel, our subsequent observations that SNPs at a distance from EREs can regulate ERalpha binding and that ER antagonists can reverse phenotypes associated with those SNPs. Specifically, we performed a series of functional genomic studies using a large panel of lymphoblastoid cell lines with dense genomic data that demonstrated that TCL1A SNPs at a distance from EREs can modulate ERalpha binding and expression of TCL1A as well as the expression of downstream immune mediators. Furthermore, 4-hydroxytamoxifen or fulvestrant could reverse these SNP-genotype effects. Similar results were found for SNPs in the IL17A cytokine and CCR6 chemokine receptor genes. These observations greatly expand our previous results and support the existence of a novel molecular mechanism that contributes to the complex interplay between estrogens and immune systems. They also raise the possibility of the pharmacological manipulation of the expression of proinflammatory cytokines and chemokines in a SNP genotype-dependent fashion. PMID- 26866886 TI - Synthesis of nitrogen doped faceted titanium dioxide in pure brookite phase with enhanced visible light photoactivity. AB - Brookite titanium dioxide (TiO2) is rarely studied, as compared with anatase and rutile phases TiO2, due to its comparatively lower photoactivity. It has been recently reported that brookite TiO2 with active facets exhibits excellent performance, however, synthesis of such faceted brookite TiO2 is difficult because of its low thermodynamic phase stability and low structural symmetric. Furthermore, like faceted anatase and rutile TiO2, faceted brookite TiO2 is not responsive to visible light due to its wide bandgap. In this study, a novel dopant, hydrazine, was introduced in the development of nitrogen doping. By applying this dopant, nitrogen doped brookite nanorods with active {120}, {111} and {011-} facets were successfully synthesized. The resultant materials exhibited remarkably enhanced visible-light photoactivity in photodegradation. PMID- 26866887 TI - Surface tailored PS/TiO2 composite nanofiber membrane for copper removal from water. AB - Polystyrene (PS)/TiO2 composite nanofiber membranes have been fabricated by electrospinning process for Cu(2+) ions removal from water. The surface properties of the polystyrene nanofibers were modulated by introducing TiO2 nanoparticles. The contact angle of the PS nanofiber membrane was found to be decreased with increasing concentration of TiO2, depicted enhanced hydrophilicity. These membranes were highly effective in adsorbing Cu(2+) ions from water. The adsorption capacity of these membranes was found to be 522 mg/g, which is significantly higher than the results reported by other researchers. This was attributed to enhanced hydrophilicity of the PS/TiO2 composite nanofiber membranes and effective adsorption property of TiO2 nanoparticles. PMID- 26866888 TI - Probing interactions of neurotransmitters with twin tailed anionic surfactant: A detailed physicochemical study. AB - Keeping in view the role of neurotransmitters (NTs) in central nervous system diseases and in controlling various physiological processes, present study is aimed to study the binding of neurotransmitters (NTs) such as norepinephrine hydrochloride (NE) and serotonin hydrochloride (5-HT) with twin tailed surfactant sodium bis(2-ethylhexyl)sulfosuccinate (AOT). Spectroscopic and electrochemical measurements combined with microcalorimetric measurements were used to characterize the interactions between AOT and NTs. Meteoric modifications to emission profile and absorption spectra of NTs upon addition of AOT are indicative of the binding of NTs with AOT. Distinct interactional states such as formation of ion-pairs, induced and regular micelles with adsorbed NTs molecules have been observed in different concentration regimes of AOT. The formation of ion-pairs from oppositely charged NTs and AOT is confirmed by the reduced absorbance, quenched fluorescence intensity and decrease in peak current (ipa) as well as shifts in peak potential (Epa) values. The stoichiometry and formation of the NTs-AOT complexes has been judged and the extent of interactions is quantitatively discussed in terms of binding constant (K) and free energy of binding (DeltaG degrees ). The enthalpy (DeltaH degrees mic) and free energy of micellization (DeltaG degrees mic) for AOT in presence and absence of NTs are determined from the enthalpy curves. PMID- 26866889 TI - Surfactant-free hydrothermal synthesis of hierarchically structured spherical CuBi2O4 as negative electrodes for Li-ion hybrid capacitors. AB - Hierarchically structured spherical CuBi2O4 particles were prepared using a facile hydrothermal method without using a surfactant over various hydrothermal reaction periods. The prepared CuBi2O4 samples were examined via X-ray diffraction (XRD), which confirmed the formation of a tetragonal crystal structure. The morphological features were analyzed using field emission scanning electron microscopy (FESEM), which elucidated the construction of the hierarchical microspherical CuBi2O4 particles. The plausible growth mechanism of the hierarchical structure was explained in terms of a time-dependent synthesis process and its crystal structure. The uniform hierarchical CuBi2O4 microspheres were used to fabricate a Li-ion hybrid capacitor (Li-HC) along with activated carbon (AC), the generated device delivers a stable specific capacitance of 26.5 F g(-1) over 1500 cycles at a high current density of 1000 mA g(-1) and a capacity retention of ~86%. The AC/CB2 Li-ion hybrid cell exhibits high energy density and power density values of 24 W h kg(-1) and 300 W kg(-1), respectively. PMID- 26866890 TI - ns or fs pulsed laser ablation of a bulk InSb target in liquids for nanoparticles synthesis. AB - Laser ablation of bulk target materials in liquids has been established as an alternative method for the synthesis of nanoparticles colloidal solutions mainly due to the fact that the synthesized nanoparticles have bare, ligand-free surfaces since no chemical precursors are used for their synthesis. InSb is a narrow band gap semiconductor which has the highest carrier mobility of any known semiconductor and nanoparticles of this material are useful in optoelectronic device fabrication. In this paper a bulk InSb target was ablated in deionized (DI) water or ethanol using a nanosecond (20 ns) or a femtosecond (90 fs) pulsed laser source, for nanoparticles synthesis. In all four cases the largest percentage of the nanoparticles are of InSb in the zincblende crystal structure with fcc lattice. Oxides of either In or Sb are also formed in the nanoparticles ensembles in the case of ns or fs ablation, respectively. Formation of an oxide of either element from the two elements of the binary bulk alloy is explained based on the difference in the ablation mechanism of the material in the case of ns or fs pulsed laser irradiation in which the slow or fast deposition of energy into the material results to mainly melting or vaporization, respectively under the present conditions of ablation, in combination with the lower melting point but higher vaporization enthalpy of In as compared to Sb. InSb in the metastable phase with orthorhombic lattice is also formed in the nanoparticles ensembles in the case of fs ablation in DI water (as well as oxide of InSb) which indicates that the synthesized nanoparticles exhibit polymorphism controlled by the type of the laser source used for their synthesis. The nanoparticles exhibit absorption which is observed to be extended in the infrared region of the spectrum. PMID- 26866891 TI - Longitudinal analytical approaches to genetic data. AB - BACKGROUND: Longitudinal phenotypic data provides a rich potential resource for genetic studies which may allow for greater understanding of variants and their covariates over time. Herein, we review 3 longitudinal analytical approaches from the Genetic Analysis Workshop 19 (GAW19). These contributions investigated both genome-wide association (GWA) and whole genome sequence (WGS) data from odd numbered chromosomes on up to 4 time points for blood pressure-related phenotypes. The statistical models used included generalized estimating equations (GEEs), latent class growth modeling (LCGM), linear mixed-effect (LME), and variance components (VC). The goal of these analyses was to test statistical approaches that use repeat measurements to increase genetic signal for variant identification. RESULTS: Two analytical methods were applied to the GAW19: GWA using real phenotypic data, and one approach to WGS using 200 simulated replicates. The first GWA approach applied a GEE-based model to identify gene based associations with 4 derived hypertension phenotypes. This GEE model identified 1 significant locus, GRM7, which passed multiple test corrections for 2 hypertension-derived traits. The second GWA approach employed the LME to estimate genetic associations with systolic blood pressure (SBP) change trajectories identified using LCGM. This LCGM method identified 5 SBP trajectories and association analyses identified a genome-wide significant locus, near ATOX1 (p = 1.0E(-8)). Finally, a third VC-based model using WGS and simulated SBP phenotypes that constrained the beta coefficient for a genetic variant across each time point was calculated and compared to an unconstrained approach. This constrained VC approach demonstrated increased power for WGS variants of moderate effect, but when larger genetic effects were present, averaging across time points was as effective. CONCLUSION: In this paper, we summarize 3 GAW19 contributions applying novel statistical methods and testing previously proposed techniques under alternative conditions for longitudinal genetic association. We conclude that these approaches when appropriately applied have the potential to: (a) increase statistical power; (b) decrease trait heterogeneity and standard error; PMID- 26866892 TI - Supersaturated polymeric micelles for oral cyclosporine A delivery: The role of Soluplus-sodium dodecyl sulfate complex. AB - Our previous study demonstrated that the retention of drug in the hydrophobic core of Soluplus micelle greatly impeded drug absorption from gastrointestinal tract. Using supersaturated polymeric micelles can improve drug release, however, insufficient maintaining of supersaturation of drug is still unfavorable for drug absorption. Here, we report adding small amount of small molecule, sodium dodecyl sulfate (SDS), to Soluplus solution can form a Soluplus-SDS complex. This complex not only showed a higher solubilization capability for the model drug cyclosporine A (CsA), but also maintained a longer period of and higher supersaturation than was achieved with Soluplus alone. The Soluplus-SDS interactions were characterized by analyzing surface tension, small-angle X-ray scattering (SAXS), fluorescence spectra, and nuclear magnetic resonance spectroscopy. The results demonstrated that the formation of Soluplus-SDS complex via SDS adsorption on hydrophobic segments of Soluplus, which have more hydrophobic domain than that of Soluplus micelle, contributed significantly to the solubilization and stabilization of supersaturated CsA. Using this amphiphilic copolymer-small molecule surfactant system, the cellular uptake and rat in vivo absorption of CsA were more effectively achieved than pure Soluplus. The area under the plasma concentration-time curve (AUC) and the maximal plasma concentration (Cmax) achieved by CsA-loaded Soluplus-SDS complex were 1.58- and 1.8-times higher than the corresponding values for CsA-loaded pure Soluplus, respectively. This study highlighted the benefits of Soluplus-SDS complex for optimizing the solubilization and oral absorption of a drug with low aqueous solubility. PMID- 26866894 TI - Near the Ferric Pseudobrookite Composition (Fe2TiO5). AB - Because of a very low thermodynamic stability, obtaining a pure monophasic compound of ferric pseudobrookite is quite difficult to achieve. Indeed, the low reticular energy of this phase leads easily to its decomposition and the occurrence of the secondary phases: hematite (Fe2O3) and/or rutile (TiO2). Samples with global composition Fe2-xTi1+xO5 (x = 0, 0.05, and 0.10) have been synthesized by the Pechini route and, thereafter, thermally treated at different temperatures. The concentrations of Fe2O3 and TiO2 secondary phases were accurately determined and correlated with the target compositions and the synthesis parameters, especially the thermal treatment temperature. As revealed by Mossbauer spectroscopy, all iron ions are at the III+ oxidation state. Thus, the formation of hematite or rutile as a secondary phase may be related to the occurrence of cationic vacancies within the pseudobrookite structure, with the amount of vacancies depending on the annealing temperature. In light of the presented results, it appears unreasonable to propose a "fixed" binary phase diagram for such a complex system. Furthermore, the occurrence of cationic vacancies induces a coloration change (darkening), preventing any industrial use of this reddish-brown pseudobrookite as a ceramic pigment. PMID- 26866893 TI - Nanoparticles prolong N-palmitoylethanolamide anti-inflammatory and analgesic effects in vivo. AB - N-Palmitoylethanolamide showed great therapeutic potential in the treatment of inflammation and pain but its unfavourable pharmacokinetics properties will hinder its use in the clinical practice. A nanotechnology-based formulation was developed to enhance the probability of N-palmitoylethanolamide therapeutic success, especially in skin disease management. Lipid nanoparticles were produced and characterized to evaluate their mean size, zeta-potential, thermal behaviour, and morphology. The ability of N-palmitoylethanolamide to diffuse across the epidermis as well as anti-inflammatory and analgesic effects were investigated. Particles had a mean size of about 150 nm and a zeta-potential of -40 mV. DSC data confirmed the solid state of the matrix and the embedding of N palmitoylethanolamide while electron microscopy have evidenced a peculiar internal structure (i.e., low-electrondense spherical objects within the matrix) that can be reliably ascribed to the presence of oil nanocompartments. Lipid nanoparticles increased N-palmitoylethanolamide percutaneous diffusion and prolonged the anti-inflammatory and analgesic effects in vivo. Lipid nanoparticles seem a good nanotechnology-based strategy to bring N palmitoylethanolamide to clinics. PMID- 26866895 TI - Role of Molecular Interactions for Synergistic Precipitation Inhibition of Poorly Soluble Drug in Supersaturated Drug-Polymer-Polymer Ternary Solution. AB - We are reporting a synergistic effect of combined Eudragit E100 and PVP K90 in precipitation inhibition of indomethacin (IND) in solutions at low polymer concentration, a phenomenon that has significant implications on the usefulness of developing novel ternary solid dispersion of poorly soluble drugs. The IND supersaturation was created by cosolvent technique, and the precipitation studies were performed in the absence and the presence of individual and combined PVP K90 and Eudragit E100. The studies were also done with PEG 8000 as a noninteracting control polymer. A continuous UV recording of the IND absorption was used to observe changes in the drug concentration over time. The polymorphic form and morphology of precipitated IND were characterized by Raman spectroscopy and scanning electron microscopy. The change in the chemical shift in solution (1)H NMR was used as novel approach to probe IND-polymer interactions. Molecular modeling was used for calculating binding energy between IND-polymer as another indication of IND-polymer interaction. Spontaneous IND precipitation was observed in the absence of polymers. Eudragit E100 showed significant inhibitory effect on nuclei formation due to stronger interaction as reflected in higher binding energy and greater change in chemical shift by NMR. PVP K90 led to significant crystal growth inhibition due to adsorption on growing IND crystals as confirmed by modified crystal habit of precipitate in the presence of PVP K90. Combination of polymers resulted in a synergistic precipitation inhibition and extended supersaturation. The NMR confirmed interaction between IND-Eudragit E100 and IND PVP K90 in solution. The combination of polymers showed similar peak shift albeit using lower polymer concentration indicating stronger interactions. The results established the significant synergistic precipitation inhibition effect upon combining Eudragit E100 and PVP K90 due to drug-polymer interaction. PMID- 26866897 TI - Metal-Free Asymmetric Synthesis of Indanes through Chiral Hypervalent Iodine(III) Mediated Ring Contraction. AB - The iodine(III)-mediated asymmetric oxidative rearrangement of 1,2 dihydronaphthalenes was investigated to prepare optically active 1-substituted indanes. The chiral hypervalent iodine species is generated in situ from a chiral aryl iodide, prepared in 94% yield in one step. This metal-free protocol was applied to different cyclic alkenes, substituted with oxygen, with nitrogen, or at position 1 with aryl or methyl. Indanes can be isolated as an acetal or alcohol in up to 78% ee. PMID- 26866896 TI - Structure and Hydration of Highly-Branched, Monodisperse Phytoglycogen Nanoparticles. AB - Phytoglycogen is a naturally occurring polysaccharide nanoparticle made up of extensively branched glucose monomers. It has a number of unusual and advantageous properties, such as high water retention, low viscosity, and high stability in water, which make this biomaterial a promising candidate for a wide variety of applications. In this study, we have characterized the structure and hydration of aqueous dispersions of phytoglycogen nanoparticles using neutron scattering. Small angle neutron scattering results suggest that the phytoglycogen nanoparticles behave similar to hard sphere colloids and are hydrated by a large number of water molecules (each nanoparticle contains between 250% and 285% of its mass in water). This suggests that phytoglycogen is an ideal sample in which to study the dynamics of hydration water. To this end, we used quasielastic neutron scattering (QENS) to provide an independent and consistent measure of the hydration number, and to estimate the retardation factor (or degree of water slow down) for hydration water translational motions. These data demonstrate a length scale dependence in the measured retardation factors that clarifies the origin of discrepancies between retardation factor values reported for hydration water using different experimental techniques. The present approach can be generalized to other systems containing nanoconfined water. PMID- 26866898 TI - Magneto-thermally activated spin-state transition in La0.95Ca0.05CoO3: magnetically-tunable dipolar glass and giant magneto-electricity. AB - The magneto-dielectric spectroscopy of La0.95Ca0.05CoO3 covering the crossover of spin states reveals the strong coupling of its spin and dipolar degrees of freedom. The signature of the spin-state transition at 30 K clearly manifests in the magnetization data at a 1 Tesla optimal field. Our Co L3,2-edge X-ray absorption spectrum on the doped specimen is consistent with its suppressed low to-intermediate spin-state transition temperature at ~30 K compared to ~150 K, documented for pure LaCoO3. The dispersive activation step in the dielectric constant with the associated relaxation peak in imaginary permittivity characterize the allied influence of coexistent spin-states on the dielectric character. Dipolar relaxation in the low-spin regime below the transition temperature is partly segmental (Vogel-Fulcher-Tamman (VFT) kinetics) and features magnetic-field tunability, whereas in the low/intermediate-spin disordered state above ~30 K, it is uncorrelated (Arrhenic kinetics) and almost impervious to the magnetic field H. Kinetics-switchover defines the dipolar-glass transition temperature Tg(H) (=27 K|0T), below which their magneto-thermally activated cooperative relaxations freeze out by the VFT temperature T0(H) (=15 K|0T). An applied magnetic field facilitates thermal activation in toggling the low spins up into the intermediate states. Consequently, the downsized dipolar glass segments in the low-spin state and the independent dipoles in the intermediate state exhibit accelerated dynamics. A critical 5 Tesla field collapses the entire relaxation kinetics into a single Arrhenic behaviour, signaling that the dipolar glass is completely devitrified under all higher fields. The magneto-electricity (ME) spanning sizeable thermo-spectral range registers diverse signatures here in kinetic, spectral, and field behaviors, in contrast to the static/perturbative ME observed close to the spin-ordering in typical multiferroics. Intrinsic magneto-dielectricity (50%) along with vanishing magneto-loss is obtained at (27 K/50 kHz)9T. The sub-linear deviant and field hysteretic split seen in above 4 Tesla suggests the emergence of robust dipoles organized into nano-clusters, induced by the internally-generated high magneto electric field. An elaborate omega-T multi-dispersions diagram maps the rich variety of phase/response patterns, revealing highly-interacting magnetic and electric moments in the system. PMID- 26866899 TI - Peptide Bond Isomerization in High-Temperature Simulations. AB - Force fields for molecular simulation are generally optimized to model macromolecules such as proteins at ambient temperature and pressure. Nevertheless, elevated temperatures are frequently used to enhance conformational sampling, either during system setup or as a component of an advanced sampling technique such as temperature replica exchange. Because macromolecular force fields are now put upon to simulate temperatures and time scales that greatly exceed their original design specifications, it is appropriate to re-evaluate whether these force fields are up to the task. Here, we quantify the rates of peptide bond isomerization in high-temperature simulations of three octameric peptides and a small fast-folding protein. We show that peptide octamers with and without proline residues undergo cis/trans isomerization every 1-5 ns at 800 K with three classical atomistic force fields (AMBER99SB-ILDN, CHARMM22/CMAP, and OPLS-AA/L). On the low microsecond time scale, these force fields permit isomerization of nonprolyl peptide bonds at temperatures >=500 K, and the CHARMM22/CMAP force field permits isomerization of prolyl peptide bonds >=400 K. Moreover, the OPLS-AA/L force field allows chiral inversion about the Calpha atom at 800 K. Finally, we show that temperature replica exchange permits cis peptide bonds developed at 540 K to subsequently migrate back to the 300 K ensemble, where cis peptide bonds are present in 2 +/- 1% of the population of Trp-cage TC5b, including up to 4% of its folded state. Further work is required to assess the accuracy of cis/trans isomerization in the current generation of protein force fields. PMID- 26866900 TI - Oxidation of Membrane Curvature-Regulating Phosphatidylethanolamine Lipid Results in Formation of Bilayer and Cubic Structures. AB - Oxidation is associated with conditions related to chronic inflammations and aging. Cubic structures have been observed in the smooth endoplasmic reticulum and mitochondrial membranes of cells under oxidative stress (e.g., tumor cells and virus-infected cells). It has been previously suspected that oxidation can result in the rearrangement of lipids from a fluid lamellar phase to a cubic structure in organelles containing membranes enriched with amphiphiles that have nonzero intrinsic curvature, such as phosphatidylethanolamine (PE) and cardiolipin. This study focuses on the oxidation of 1,2-dioleoyl-sn-glycero-3 phosphoethanolamine (DOPE), a lipid that natively forms an inverted hexagonal phase at physiological conditions. The oxidized samples contain an approximately 3:2 molar ratio of nonoxidized to oxidized DOPE. Optical microscopy images collected during the hydration of this mixture from a dried film suggest that the system evolves into a coexistence of a stable fluid lamellar phase and transient square lattice structures with unit cell sizes of 500-600 nm. Small-angle X-ray scattering of the same lipid mixture yielded a body-centered Im3m cubic phase with the lattice parameter of 14.04 nm. On average, the effective packing parameter of the oxidized DOPE species was estimated to be 0.657 +/- 0.069 (standard deviation). This suggests that the oxidation of PE leads to a group of species with inverted molecular intrinsic curvature. Oxidation can create amphiphilic subpopulations that potently impact the integrity of the membrane, since negative Gaussian curvature intrinsic to cubic phases can enable membrane destabilization processes. PMID- 26866901 TI - Borderline personality disorder and self-conscious affect: Too much shame but not enough guilt? AB - Shame has emerged as a particularly relevant emotion to the maintenance and exacerbation of borderline personality disorder (BPD) features; however, little attention has been paid to the potentially differing effects of other forms of self-conscious affect. While guilt has been demonstrated to have adaptive functions in the social psychology literature, it has not been previously explored whether a lack of socially adaptive guilt might also contribute to BPD related dysfunction. The present study examined the relationship between BPD features and self-conscious emotions in a sample of undergraduate students (n = 839). Increased shame and decreased guilt independently accounted for significant variance in the association between BPD features and anger, hostility, and externalization of blame. Only increased shame significantly mediated the association between BPD features and anger rumination, and only decreased guilt significantly mediated the relationship between BPD features and aggression. These findings suggest BPD and its associated problems with anger and externalizing may be characterized not only by high levels of shame, but also by lower levels of guilt. Clinical implications include the need to differentiate between self-conscious emotions and teach adaptive responses to warranted guilt. (PsycINFO Database Record PMID- 26866902 TI - Expanding the plasmonic response of bimetallic nanoparticles by laser seeding. AB - This work explores a cost-effective route to enhance the tuning range of the optical response of metal nanostructures on substrates beyond the ranges that are achievable through the nanostructure dimensions, composition or dewetting processes. The new route (laser seeding) uses single nanosecond laser pulses to induce dewetting in regions of a metal layer deposited on a glass substrate followed by the deposition of a second metal layer, both layers being deposited by pulsed laser deposition. In order to show the possibilities of this new route, we have chosen that the two metals were different, namely Ag and Au. The comparison of the optical response of these regions to those that were laser irradiated after deposition of the second metal layer shows that while nanoalloyed nanoparticles (NPs) are formed in the latter case, the NPs produced in the former case have a heterogeneous structure. The interface between the two metals is either sharp or a narrow region where they have mixed depending on the laser fluence used. While the nanoalloyed NPs exhibit a single, narrow surface plasmon resonance (SPR), the heterogeneous NPs show broader SPRs that peak in the near infrared and depending on conditions exhibit even two clear SPRs. The laser seeding approach in the conditions used in this work allows for the expansion of the tuning range of the color to the blue-green region, i.e. beyond the region that can be achieved through nanoalloyed NPs (yellow-red region). In addition, the results presented foresee the laser seeding route as a means to produce round and almost isolated NPs in an enhanced range of diameters. PMID- 26866904 TI - Comparison of ECG-based physiological markers for hypoxia in a preterm ovine model. AB - BACKGROUND: Current methods for assessing perinatal hypoxic conditions did not improve infant outcomes. Various waveform-based and interval-based ECG markers have been suggested, but not directly compared. We compare performance of ECG markers in a standardized ovine model for fetal hypoxia. METHODS: Sixty-nine fetal sheep of 0.7 gestation had ECG recorded 4 h before, during, and 4 h after a 25-min period of umbilical cord occlusion (UCO), leading to severe hypoxia. Various ECG markers were calculated, among which were heart rate (HR), HR corrected ventricular depolarization/repolarization interval (QTc), and ST segment analysis (STAN) episodic and baseline rise markers, analogue to clinical STAN device alarms. Performance of interval- and waveform-based ECG markers was assessed by correlating predicted and actual hypoxic/normoxic state. RESULTS: Of the markers studied, HR and QTc demonstrated high sensitivity (>=86%), specificity (>=96%), and positive predictive value (PPV) (>=86%) and detected hypoxia in >=90% of fetuses at 4 min after UCO. In contrast, STAN episodic and baseline rise markers displayed low sensitivity (<=20%) and could not detect severe fetal hypoxia in 65 and 28% of the animals, respectively. CONCLUSION: Interval-based HR and QTc markers could assess the presence of severe hypoxia. Waveform-based STAN episodic and baseline rise markers were ineffective as markers for hypoxia. PMID- 26866905 TI - The interrelationship of recruitment maneuver at birth, antenatal steroids, and exogenous surfactant on compliance and oxygenation in preterm lambs. AB - BACKGROUND: To describe the interrelationship between antenatal steroids, exogenous surfactant, and two approaches to lung recruitment at birth on oxygenation and respiratory system compliance (Cdyn) in preterm lambs. METHODS: Lambs (n = 63; gestational age 127 +/- 1 d) received either surfactant at 10-min life (Surfactant), antenatal corticosteroids (Steroid), or neither (Control). Within each epoch lambs were randomly assigned to a 30-s 40 cmH2O sustained inflation (SI) or an initial stepwise positive end-expiratory pressure (PEEP) open lung ventilation (OLV) maneuver at birth. All lambs then received the same management for 60-min with alveolar-arterial oxygen difference (AaDO2) and Cdyn measured at regular time points. RESULTS: Overall, the OLV strategy improved Cdyn and AaDO2 (all epochs except Surfactant) compared to SI (all P < 0.05; two-way ANOVA). Irrespective of strategy, Cdyn was better in the Steroid group in the first 10 min (all P < 0.05). Thereafter, Cdyn was similar to Steroid epoch in the OLV + Surfactant, but not SI + Surfactant group. OLV influenced the effect of steroid and surfactant (P = 0.005) on AaDO2 more than SI (P = 0.235). CONCLUSIONS: The antenatal state of the lung influences the type and impact of a recruitment maneuver at birth. The effectiveness of surfactant maybe enhanced using PEEP-based time-dependent recruitment strategies rather than approaches solely aimed at initial lung liquid clearance. PMID- 26866903 TI - Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy. AB - Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease. PMID- 26866909 TI - Thieno[3,4-b]pyrazine as an Electron Deficient pi-Bridge in D-A-pi-A DSCs. AB - Thieno[3,4-b]pyrazine (TPz) is examined as an electron deficient pi-bridge enabling near-infrared (NIR) spectral access in dye-sensitized solar cells (DSCs). Seven dissymmetric dyes for DSCs were synthesized (NL2-NL8) with TPz as the pi-bridge utilizing palladium catalyzed C-H activation methodology. C-H bond cross-coupling was uniquely effective among the cross-couplings and electrophilic aromatic substitution reactions analyzed in monofunctionalizing the TPz building block. The TPz-based NL2-NL8 dyes examine the effects of various donors, pi spacers, and acceptors within the donor-pi bridge-acceptor (D-pi-A) dye design. Proaromatic TPz stabilizes the excited-state oxidation potential (E(s+/s*)) of the dyes by maintaining aromaticity upon excitation of the dye molecule. This leads to concise conjugated systems capable of accessing the NIR region. Through judicious structural modifications, dye band gaps were reduced to 1.48 eV, and power conversion efficiencies (PCEs) reached 7.1% in this first generation TPz dye series. PMID- 26866907 TI - Iron is prioritized to red blood cells over the brain in phlebotomized anemic newborn lambs. AB - BACKGROUND: Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron's role in neurodevelopment. METHODS: Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5 mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy. RESULTS: Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = -0.70; P < 0.01) and as a function of reticulocyte count (r = -0.63; P < 0.05). CONCLUSION: Phlebotomy-induced negative iron balance limits iron availability to the developing brain. PMID- 26866910 TI - WITHDRAWN: Inhaled bronchodilators for cystic fibrosis. PMID- 26866906 TI - Childhood obesity-related endothelial dysfunction: an update on pathophysiological mechanisms and diagnostic advancements. AB - Childhood obesity jeopardizes a healthy future for our society's children as it is associated with increased cardiovascular morbidity and mortality later on in life. Endothelial dysfunction, the first step in the development of atherosclerosis, is already present in obese children and may well represent a targetable risk factor. Technological advancements in recent years have facilitated noninvasive measurements of endothelial homeostasis in children. Thereby this topic ultimately starts to get the attention it deserves. In this paper, we aim to summarize the latest insights on endothelial dysfunction in childhood obesity. We discuss methodological advancements in peripheral endothelial function measurement and newly identified diagnostic markers of vascular homeostasis. Finally, future challenges and perspectives are set forth on how to efficiently tackle the catastrophic rise in cardiovascular morbidity and mortality that will be inflicted on obese children if they are not treated optimally. PMID- 26866908 TI - Comparing apples with apples: it is time for standardized reporting of neonatal nutrition and growth studies. AB - The ultimate goal of neonatal nutrition care is optimal growth, neurodevelopment, and long-term health for preterm babies. International consensus is that increased energy and protein intakes in the neonatal period improve growth and neurodevelopment, but after more than 100 y of research the optimum intakes of energy and protein remain unknown. We suggest an important factor contributing to the lack of progress is the lack of a standardized approach to reporting nutritional intake data and growth in the neonatal literature. We reviewed randomized controlled trials and observational studies documented in MEDLINE and the Web of Science from 2008 to 2015 that compared approximately 3 vs. 4 g.kg( 1).d(-1) protein for preterm babies in the first month after birth. Consistency might be expected in the calculation of nutritional intake and assessment of growth outcomes in this relatively narrow scope of neonatal nutrition research. Twenty-two studies were reviewed. There was substantial variation in methods used to estimate and calculate nutritional intakes and in the approaches used in reporting these intakes and measures of infant growth. Such variability makes comparisons amongst studies difficult and meta-analysis unreliable. We propose the StRONNG Checklist-Standardized Reporting Of Neonatal Nutrition and Growth to address these issues. PMID- 26866911 TI - Muscle Activity Adaptations to Spinal Tissue Creep in the Presence of Muscle Fatigue. AB - AIM: The aim of this study was to identify adaptations in muscle activity distribution to spinal tissue creep in presence of muscle fatigue. METHODS: Twenty-three healthy participants performed a fatigue task before and after 30 minutes of passive spinal tissue deformation in flexion. Right and left erector spinae activity was recorded using large-arrays surface electromyography (EMG). To characterize muscle activity distribution, dispersion was used. During the fatigue task, EMG amplitude root mean square (RMS), median frequency and dispersion in x- and y-axis were compared before and after spinal creep. RESULTS: Important fatigue-related changes in EMG median frequency were observed during muscle fatigue. Median frequency values showed a significant main creep effect, with lower median frequency values on the left side under the creep condition (p<=0.0001). A significant main creep effect on RMS values was also observed as RMS values were higher after creep deformation on the right side (p = 0.014); a similar tendency, although not significant, was observed on the left side (p = 0.06). A significant creep effects for x-axis dispersion values was observed, with higher dispersion values following the deformation protocol on the left side (p<=0.001). Regarding y-axis dispersion values, a significant creep x fatigue interaction effect was observed on the left side (p = 0.016); a similar tendency, although not significant, was observed on the right side (p = 0.08). CONCLUSION: Combined muscle fatigue and creep deformation of spinal tissues led to changes in muscle activity amplitude, frequency domain and distribution. PMID- 26866913 TI - Towards a Metropolitan Fundamental Diagram Using Travel Survey Data. AB - Using travel diary data from 2000-2001 and 2010-2012 this research examines fundamental traffic relationships at the metropolitan level. The results of this paper can help to explain the causes of some traffic phenomena. Network average speed by time of day can be explained by trip length and cumulative number of vehicles on the road. A clockwise hysteresis loop is found in the Metropolitan Fundamental Diagram in the morning period and a reverse process happens in the afternoon. PMID- 26866912 TI - Risk Factors for Enterovirus A71 Seropositivity in Rural Indigenous Populations in West Malaysia. AB - Enterovirus A71 (EV-A71), which is transmitted by the fecal-oral route, causes hand, foot and mouth disease and, rarely, severe neurological complications. In Malaysia, the indigenous rural community (Orang Asli) has a high prevalence of parasitic diseases due to poor sanitation, water supply and hygiene practices. This cross-sectional study compared the seroepidemiology of EV-A71 among rural Orang Asli and urban Kuala Lumpur populations in West Malaysia, and determined the risk factors associated with EV-A71 seropositivity in rural Orang Asli. Seropositive rates were determined by neutralization assay. EV-A71 seropositivity was strongly associated with increasing age in both populations. Rural Orang Asli children <=12 years had significantly higher EV-A71 seropositivity rates than urban Kuala Lumpur children (95.5% vs 57.6%, P < 0.001), and also higher rates in the age groups of 1-3, 4-6 and 7-12 years. Multivariate analysis confirmed that age <=12 years (adjusted OR 8.1, 95% CI 3.2-20.7, P < 0.001) and using untreated water (adjusted OR 6.2, 95% CI 2.3-16.6, P < 0.001) were independently associated with EV-A71 seropositivity in the Orang Asli population. Supply of clean drinking water may reduce the risk of EV-A71 infection. With significantly higher EV-A71 seropositive rates, younger rural children should be a priority target for future vaccination programs in Malaysia. PMID- 26866914 TI - The March towards a Vaccine for Congenital CMV: Rationale and Models. PMID- 26866915 TI - Tunneling Interlayer for Efficient Transport of Charges in Metal Oxide Electrodes. AB - Due to the limited electronic conductivity, the application of many metal oxides that may have attractive (photo)-electrochemical properties has been limited. Regarding these issues, incorporating low-dimensional conducting scaffolds into the electrodes or supporting the metal oxides onto the conducting networks are common approaches. However, some key electronic processes like interfacial charge transfer are far from being consciously concerned. Here we use a carbon-TiO2 contact as a model system to demonstrate the electronic processes occurring at the metal-semiconductor interface. To minimize the energy dissipation for fast transfer of electrons from semiconductor to carbon scaffolds, facilitating electron tunneling while avoiding high energy-consuming thermionic emission is desired, according to our theoretical simulation of the voltammetric behaviors. To validate this, we manage to sandwich ultrathin TiO2 interlayers with heavy electronic doping between the carbon conductors and dopant-free TiO2. The radially graded distribution of the electronic doping along the cross-sectional direction of carbon conductor realized by immobilizing the dopant species on the carbon surface can minimize the energy consumption for contacts to both the carbon and the dopant-free TiO2. Our strategy provides an important requirement for metal oxide electrode design. PMID- 26866916 TI - Generation and Characterisation of a Pax8-CreERT2 Transgenic Line and a Slc22a6 CreERT2 Knock-In Line for Inducible and Specific Genetic Manipulation of Renal Tubular Epithelial Cells. AB - Genetically relevant mouse models need to recapitulate the hallmarks of human disease by permitting spatiotemporal gene targeting. This is especially important for replicating the biology of complex diseases like cancer, where genetic events occur in a sporadic fashion within developed somatic tissues. Though a number of renal tubule targeting mouse lines have been developed their utility for the study of renal disease is limited by lack of inducibility and specificity. In this study we describe the generation and characterisation of two novel mouse lines directing CreERT2 expression to renal tubular epithelia. The Pax8-CreERT2 transgenic line uses the mouse Pax8 promoter to direct expression of CreERT2 to all renal tubular compartments (proximal and distal tubules as well as collecting ducts) whilst the Slc22a6-CreERT2 knock-in line utilises the endogenous mouse Slc22a6 locus to specifically target the epithelium of proximal renal tubules. Both lines show high organ and tissue specificity with no extrarenal activity detected. To establish the utility of these lines for the study of renal cancer biology, Pax8-CreERT2 and Slc22a6-CreERT2 mice were crossed to conditional Vhl knockout mice to induce long-term renal tubule specific Vhl deletion. These models exhibited renal specific activation of the hypoxia inducible factor pathway (a VHL target). Our results establish Pax8-CreERT2 and Slc22a6-CreERT2 mice as valuable tools for the investigation and modelling of complex renal biology and disease. PMID- 26866917 TI - Radial Frequency Analysis of Contour Shapes in the Visual Cortex. AB - Cumulative psychophysical evidence suggests that the shape of closed contours is analysed by means of their radial frequency components (RFC). However, neurophysiological evidence for RFC-based representations is still missing. We investigated the representation of radial frequency in the human visual cortex with functional magnetic resonance imaging. We parametrically varied the radial frequency, amplitude and local curvature of contour shapes. The stimuli evoked clear responses across visual areas in the univariate analysis, but the response magnitude did not depend on radial frequency or local curvature. Searchlight based, multivariate representational similarity analysis revealed RFC specific response patterns in areas V2d, V3d, V3AB, and IPS0. Interestingly, RFC-specific representations were not found in hV4 or LO, traditionally associated with visual shape analysis. The modulation amplitude of the shapes did not affect the responses in any visual area. Local curvature, SF-spectrum and contrast energy related representations were found across visual areas but without similar specificity for visual area that was found for RFC. The results suggest that the radial frequency of a closed contour is one of the cortical shape analysis dimensions, represented in the early and mid-level visual areas. PMID- 26866918 TI - Robust CPD Algorithm for Non-Rigid Point Set Registration Based on Structure Information. AB - Recently, the Coherent Point Drift (CPD) algorithm has become a very popular and efficient method for point set registration. However, this method does not take into consideration the neighborhood structure information of points to find the correspondence and requires a manual assignment of the outlier ratio. Therefore, CPD is not robust for large degrees of degradation. In this paper, an improved method is proposed to overcome the two limitations of CPD. A structure descriptor, such as shape context, is used to perform the auxiliary calculation of the correspondence, and the proportion of each GMM component is adjusted by the similarity. The outlier ratio is formulated in the EM framework so that it can be automatically calculated and optimized iteratively. The experimental results on both synthetic data and real data demonstrate that the proposed method described here is more robust to deformation, noise, occlusion, and outliers than CPD and other state-of-the-art algorithms. PMID- 26866919 TI - Intrapericardial Delivery of Cardiosphere-Derived Cells: An Immunological Study in a Clinically Relevant Large Animal Model. AB - INTRODUCTION: The intrapericardial delivery has been defined as an efficient method for pharmacological agent delivery. Here we hypothesize that intrapericardial administration of cardiosphere-derived cells (CDCs) may have an immunomodulatory effect providing an optimal microenvironment for promoting cardiac repair. To our knowledge, this is the first report studying the effects of CDCs for myocardial repair using the intrapericardial delivery route. MATERIAL AND METHODS: CDCs lines were isolated, expanded and characterized by flow cytometry and PCR. Their differentiation ability was determined using specific culture media and differential staining. 300,000 CDCs/kg were injected into the pericardial space of a swine myocardial infarcted model. Magnetic resonance imaging, biochemical analysis of pericardial fluid and plasma, cytokine measurements and flow cytometry analysis were performed. RESULTS: Our results showed that, phenotype and differentiation behavior of porcine CDCs were equivalent to previously described CDCs. Moreover, the intrapericardial administration of CDCs fulfilled the safety aspects as non-adverse effects were reported. Finally, the phenotypes of resident lymphocytes and TH1 cytokines in the pericardial fluid were significantly altered after CDCs administration. CONCLUSIONS: The pericardial fluid could be considered as a safe and optimal vehicle for CDCs administration. The observed changes in the studied immunological parameters could exert a modulation in the inflammatory environment of infarcted hearts, indirectly benefiting the endogenous cardiac repair. PMID- 26866921 TI - Gyroscopic corrections improve wearable sensor data prior to measuring dynamic sway in the gait of people with Multiple Sclerosis. AB - Accelerometers are incorporated into many consumer devices providing new ways to monitor gait, mobility, and fall risk. However, many health benefits have not been realised because of issues with data quality that results from gravitational 'cross-talk' when the wearable device is tilted. Here we present an adaptive filter designed to improve the quality of accelerometer data prior to measuring dynamic pelvic sway patterns during a six minute walk test in people with and without Multiple Sclerosis (MS). Optical motion capture was used as the gold standard. Improved wearable device accuracy (<=4.4% NRMSE) was achieved using gyroscopic corrections and scaling filter thresholds by step frequency. The people with MS presented significantly greater pelvis sway range to compensate for their lower limb weaknesses and joint contractures. The visualisation of asymmetric pelvic sway in people with MS illustrates the potential to better understand their mobility impairments for reducing fall risk. PMID- 26866922 TI - The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function. AB - This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H2 S) in physiology of the upper and lower urinary tract. NO and H2 S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H2 S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter. PMID- 26866920 TI - The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study. AB - BACKGROUND: Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. METHODS: We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5-24.99), overweight (25-29.9), mild obesity (30-34.9) and moderate/severe obesity (>= 35); we measured abdominal obesity using a waist circumference of >=102 and >= 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. RESULTS: The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95% confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. CONCLUSIONS: Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR QoL. PMID- 26866923 TI - Development of an Indirect ELISA for Serological Diagnosis of Bovine herpesvirus 5. AB - Bovine herpesviruses 1 and 5 (BoHV-1 and BoHV-5) are economically important pathogens, associated with a variety of clinical syndromes, including respiratory and genital disease, reproductive failure and meningoencephalitis. The standard serological assay to diagnose BoHV-1 and BoHV-5 infections is the virus neutralization test (VNT), a time consuming procedure that requires manipulation of infectious virus. In the present study a highly sensitive and specific single dilution indirect ELISA was developed using recombinant glycoprotein D from BoHV 5 as antigen (rgD5ELISA). Bovine serum samples (n = 450) were screened by VNT against BoHV-5a and by rgD5ELISA. Compared with the VNT, the rgD5ELISA demonstrated accuracy of 99.8%, with 100% sensitivity, 96.7% specificity and coefficient of agreement between the tests of 0.954. The rgD5ELISA described here shows excellent agreement with the VNT and is shown to be a simple, convenient, specific and highly sensitive virus-free assay for detection of serum antibodies to BoHV-5. PMID- 26866924 TI - Novel Role of Src in Priming Pyk2 Phosphorylation. AB - Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family of non-receptor tyrosine kinases and plays an important role in diverse cellular events downstream of the integrin-family of receptors, including cell migration, proliferation and survival. Here, we have identified a novel role for Src kinase in priming Pyk2 phosphorylation and subsequent activation upon cell attachment on the integrin-ligand fibronectin. By using complementary methods, we show that Src activity is indispensable for the initial Pyk2 phosphorylation on the Y402 site observed in response to cell attachment. In contrast, the initial fibronectin-induced autophosphorylation of FAK in the homologous Y397 site occurs in a Src-independent manner. We demonstrate that the SH2-domain of Src is required for Src binding to Pyk2 and for Pyk2 phosphorylation at sites Y402 and Y579. Moreover, Y402 phosphorylation is a prerequisite for the subsequent Y579 phosphorylation. While this initial phosphorylation of Pyk2 by Src is independent of Pyk2 kinase activity, subsequent autophosphorylation of Pyk2 in trans is required for full Pyk2 phosphorylation and activation. Collectively, our studies reveal a novel function of Src in priming Pyk2 (but not FAK) phosphorylation and subsequent activation downstream of integrins, and shed light on the signaling events that regulate the function of Pyk2. PMID- 26866925 TI - Heme oxygenase 1 controls early innate immune response of macrophages to Salmonella Typhimurium infection. AB - Macrophages are central for the immune control of intracellular microbes. Heme oxygenase 1 (HO-1, hmox) is the first and rate limiting enzyme in the breakdown of heme originating from degraded senescent erythrocytes and heme-proteins, yielding equal amounts of iron, carbon monoxide and biliverdin. HO-1 is strongly up-regulated in macrophages in response to inflammatory signals, including bacterial endotoxin. In view of the essential role of iron for the growth and proliferation of intracellular bacteria along with known effects of the metal on innate immune function, we examined whether HO-1 plays a role in the control of infection with the intracellular bacterium Salmonella Typhimurium. We studied the course of infection in stably-transfected murine macrophages (RAW264.7) bearing a tetracycline-inducible plasmid producing hmox shRNA and in primary HO-1 knockout macrophages. While uptake of bacteria into macrophages was not affected, a significantly reduced survival of intracellular Salmonella was observed upon hmox knockdown or pharmacological hmox inhibition, which was independent of Nramp1 functionality. This could be traced to limitation of iron availability for intramacrophage bacteria along with enhanced stimulation of innate immune effector pathways, including the formation of reactive oxygen and nitrogen species and increased TNF-alpha expression. Mechanistically, these latter effects result from intracellular iron limitation with subsequent activation of NF-kappaB and further inos, tnfa and p47phox transcription along with reduced formation of the anti-inflammatory and radical scavenging molecules, CO and biliverdin as a consequence of HO-1 silencing. Taken together our data provide novel evidence that the infection-driven induction of HO-1 exerts detrimental effects in the early control of Salmonella infection, whereas hmox inhibition can favourably modulate anti-bacterial immune effector pathways of macrophages and promote bacterial elimination. PMID- 26866926 TI - Micro-scale Spatial Clustering of Cholera Risk Factors in Urban Bangladesh. AB - Close interpersonal contact likely drives spatial clustering of cases of cholera and diarrhea, but spatial clustering of risk factors may also drive this pattern. Few studies have focused specifically on how exposures for disease cluster at small spatial scales. Improving our understanding of the micro-scale clustering of risk factors for cholera may help to target interventions and power studies with cluster designs. We selected sets of spatially matched households (matched sets) near cholera case households between April and October 2013 in a cholera endemic urban neighborhood of Tongi Township in Bangladesh. We collected data on exposures to suspected cholera risk factors at the household and individual level. We used intra-class correlation coefficients (ICCs) to characterize clustering of exposures within matched-sets and households, and assessed if clustering depended on the geographical extent of the matched-sets. Clustering over larger spatial scales was explored by assessing the relationship between matched-sets. We also explored whether different exposures tended to appear together in individuals, households, and matched-sets. Household level exposures, including: drinking municipal supplied water (ICC = 0.97, 95%CI = 0.96, 0.98), type of latrine (ICC = 0.88, 95%CI = 0.71, 1.00), and intermittent access to drinking water (ICC = 0.96, 95%CI = 0.87, 1.00) exhibited strong clustering within matched-sets. As the geographic extent of matched-sets increased, the concordance of exposures within matched-sets decreased. Concordance between matched-sets of exposures related to water supply was elevated at distances of up to approximately 400 meters. Household level hygiene practices were correlated with infrastructure shown to increase cholera risk. Co-occurrence of different individual level exposures appeared to mostly reflect the differing domestic roles of study participants. Strong spatial clustering of exposures at a small spatial scale in a cholera endemic population suggests a possible role for highly targeted interventions. Studies with cluster designs in areas with strong spatial clustering of exposures should increase sample size to account for the correlation of these exposures. PMID- 26866927 TI - Multiwalled Carbon Nanotubes Inhibit Tumor Progression in a Mouse Model. AB - Understanding the molecular mechanisms underlying the biosynthetic interactions between particular nanomaterials with specific cells or proteins opens new alternatives in nanomedicine and nanotoxicology. Multiwalled carbon nanotubes (MWCNTs) have long been explored as drug delivery systems and nanomedicines against cancer. There are high expectations for their use in therapy and diagnosis. These filaments can translocate inside cultured cells and intermingle with the protein nanofilaments of the cytoskeleton, interfering with the biomechanics of cell division mimicking the effect of traditional microtubule binding anti-cancer drugs such as paclitaxel. Here, it is shown how MWCNTs can trigger significant anti-tumoral effects in vivo, in solid malignant melanomas produced by allograft transplantation. Interestingly, the MWCNT anti-tumoral effects are maintained even in solid melanomas generated from paclitaxel resistant cells. These findings provide great expectation in the development of groundbreaking adjuvant synthetic microtubule-stabilizing chemotherapies to overcome drug resistance in cancer. PMID- 26866928 TI - Endovascular Management of Acute Ischemic Strokes with Tandem Occlusions. AB - BACKGROUND: Ischemic strokes with tandem occlusions are associated with a poor prognosis. Recent studies demonstrating the effectiveness of endovascular treatment for large vessel occlusions have shown less impressive results in patients with tandem occlusions than in those with isolated intracranial occlusions. Also, the indications and effects of carotid stenting remain unclear. METHODS: From a prospectively gathered registry, we analyzed data of 70 consecutive patients who underwent mechanical endovascular treatment for acute stroke with tandem occlusions from November 2011 to August 2014. Clinical (including demographics, National Institutes of Health Stroke Scale (NIHSS), and stroke etiology), imaging (including diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score), and endovascular treatment data were assessed and reviewed in consensus by 2 observers. Good clinical outcome was defined as a modified Rankin Scale of <=2 at 3-month follow-up. RESULTS: At 3 month follow-up, 50.8% had a poor clinical outcome, including death in 13.4%. Lower NIHSS (initial, at day 1, and at discharge) and successful recanalization (thrombolysis in cerebral infarction 2b-3) were associated with a good clinical outcome (p < 0.05). There were no statistically significant differences between patients with a good or poor clinical outcome in terms of intravenous (IV) tissue plasminogen activator use, delay between symptom onset and recanalization, and endovascular technique including the carotid stenting. CONCLUSIONS: Despite the recent randomized control trials demonstrating the effectiveness of thrombectomy, there is still a research gap about tandem occlusions. This subtype of stroke, which usually responds poorly to IV thrombolysis, is also difficult to treat by endovascular means. Guidelines for the endovascular management of tandem occlusions are needed. PMID- 26866929 TI - A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium-based MRI contrast agents. AB - Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)-based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R1) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)-induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance(r), MultiHance(r) and Magnevist(r). Urine was collected for 24 h after the oral ingestion of the Gd-containing CA at day 3-4 (severe damage stage) and day 8-9 (recovery stage) after treatment with DSS. The Gd content in urine measured by (1)H relaxometry was confirmed by inductively coupled plasma-mass spectrometry (ICP-MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5-3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice. PMID- 26866930 TI - Effect of Angiotensin-(1-7) on Aortic Response, TNF-alpha, IL-1beta and Receptor for Advanced Glycation Endproduct in Rat's Adjuvant-Induced Arthritis. AB - Altered vascular reactivity due to endothelial dysfunction, consequent to vascular damage, is observed in rheumatoid arthritis. We investigated the effect of angiotensin (Ang)-(1-7) on vasculature changes in arthritis induced by complete Freund's adjuvant in male Wistar rats. Arthritis decreased soluble receptor for advanced glycation end products (sRAGE) whereas elevated aortic RAGE expression, increased interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), systolic blood pressure and the contractility induced by phenylephrine and KCl. Moreover, arthritis decreased the relaxing effect of acetylcholine. Neither arthritis nor Ang-(1-7) altered sodium nitroprusside relaxation. Ang-(1-7) reversed the effect of arthritis on TNF-alpha, sRAGE and RAGE expression without any effect on the IL-1beta. Ang-(1-7) decreased phenylephrine and KCl contractility, especially in the endothelial-denuded aorta, whereas increased acetylcholine relaxation in the endothelial-intact aorta. Ang (1-7) could find its place in the treatment protocol of arthritis and vascular diseases. PMID- 26866931 TI - Expression of AQP1 Was Associated with Apoptosis and Survival of Patients in Gastric Adenocarcinoma. AB - RATIONALE AND OBJECTIVE: Recently, interest in the role of aquaporin 1 (AQP1) in human gastrointestinal carcinogenesis has developed. However, to date no studies have examined relationships between AQP1 expression and specific characteristics of gastric adenocarcinoma. METHODS: We investigated 109 specimens of primary gastric adenocarcinoma and their corresponding normal gastric mucosa using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine AQP1 expression. We then evaluated disease free survival (DFS) and overall survival (OS) in these patients in association with AQP1 expression. RESULTS: Both immunohistochemical and RT-PCR analyses identified increased AQP1 expression in tumors from patients with gastric adenocarcinoma (p < 0.001). The 3 year DFS and OS rates were higher in the AQP1-negative group than in the positive group (DFS: 77.2 vs. 52.8%, p < 0.001; OS: 85.1 vs. 70.7%, p < 0.001). The 5-year DFS and OS rates exhibited a similar trend (p < 0.001). Subgroup analysis of patients with early gastric adenocarcinoma (stages I and II) revealed a total 5 year OS of 90.0%, with 5-year OS being higher in the AQP1-negative group than in the positive group (95.2 vs. 84.2%). Furthermore, incidence of tumor recurrence following surgical treatment was significantly higher in the AQP1-positive group (4/19, 21.1%) compared with the negative group (0/21, 0%). CONCLUSIONS: Our study demonstrates that AQP1 plays an important role in gastric adenocarcinoma and may therefore represent a novel therapeutic target and prognostic marker in this disease. PMID- 26866934 TI - Does Renin-Angiotensin System Blockade Protect Lupus Nephritis Patients From Atherosclerotic Cardiovascular Events? A Case-Control Study. AB - OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used as an adjuvant treatment in lupus nephritis (LN) patients with proteinuria. The primary aim of this study was to discover whether ACE inhibitors/ARBs have an atheroprotective effect similar to other, at risk, populations. METHODS: A total of 144 patients (cases; mean +/- SD age at onset 34 +/- 12.1 years, followup 14.9 +/- 8.6 years) with LN who were treated with ACE inhibitors/ARBs for at least 5 years were enrolled. The control group comprised 301 LN patients (mean +/- SD age at onset 34.1 +/- 13.2 years, followup 13.4 +/- 7.9 years) with no such treatment. All patients were followed for the occurrence of atherosclerotic cardiovascular events (CVEs), consisting of transient ischemic attack and stroke, angina, myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), and congestive heart failure. Patients with preexisting CVEs were excluded. RESULTS: There were no significant differences in the cumulative occurrence of CVEs (9.7% for treated versus 8.6% for nontreated patients; P = 0.708); however, hard events (stroke, myocardial infarction, CABG, and PTCA) were less frequent in treated patients (4.17% versus 5.32%). Cases were more frequently hypertensive (100% versus 52.8%; P < 0.001) and diabetic (10.4% versus 4.7%; P = 0.021), whereas controls more frequently had hypercholesterolemia (27.9% versus 18.1%; P = 0.024) and elevated triglycerides (14% versus 4.9%; P = 0.004); other variables did not differ significantly. Regression analysis failed to confirm ACE inhibitor/ARB nonuse as an important predictor of future CVEs. CONCLUSION: Our data do not support the hypothesis that ACE inhibitors/ARBs may be protective against atherosclerotic CVEs in LN patients. PMID- 26866933 TI - Transanal submucosal polyacrylamide gel injection treatment of anal incontinence: a randomized controlled trial. AB - INTRODUCTION: The efficacious and safe use of transurethral injections of polyacrylamide hydrogel (Bulkamid((r))) in women with stress urinary incontinence suggests that it may be suitable also for treatment of anal incontinence. We aimed to determine the effectiveness and safety of polyacrylamide hydrogel when used as a transanal submucosal bulking agent in women with anal incontinence. MATERIALS AND METHODS: Thirty women with a diagnosis of anal incontinence and a Cleveland Clinic Incontinence Score (CCIS) >10 were randomized to three different techniques of transanal submucosal injections using polyacrylamide hydrogel. Follow up was performed at 2, 6 and 12 months using CCIS and the Fecal Incontinence Quality of Life scale (FIQL). RESULTS: In all, 29 of the 30 women completed the follow up. Approximately half of the women requested a re-injection at the 6-month visit. The overall CCIS improved significantly from baseline (14.7. SD 2.5) to 1 year (12.4. SD 3.1) (p = 0.003). There was a significant improvement with regard to the occurrence of loose fecal incontinence (p = 0.014) but not for solid fecal incontinence (p = 0.28). At 1 year the FIQL domains of coping-behavior, depression, and embarrassment showed significant improvements (p = 0.012, p = 0.007 and p = 0.007, respectively). We recorded no adverse events related either to the injection technique or the biomaterial. There were no significant differences between the treatment groups in either CCIS or FIQL scores. CONCLUSION: Transanal submucosal injection of polyacrylamide hydrogel resulted in a modest although significant overall improvement in anal incontinence symptom scores with corresponding improvements in several domains of quality of life, regardless of injection volume. PMID- 26866932 TI - Cross-talk between circadian clocks, sleep-wake cycles, and metabolic networks: Dispelling the darkness. AB - Integration of knowledge concerning circadian rhythms, metabolic networks, and sleep-wake cycles is imperative for unraveling the mysteries of biological cycles and their underlying mechanisms. During the last decade, enormous progress in circadian biology research has provided a plethora of new insights into the molecular architecture of circadian clocks. However, the recent identification of autonomous redox oscillations in cells has expanded our view of the clockwork beyond conventional transcription/translation feedback loop models, which have been dominant since the first circadian period mutants were identified in fruit fly. Consequently, non-transcriptional timekeeping mechanisms have been proposed, and the antioxidant peroxiredoxin proteins have been identified as conserved markers for 24-hour rhythms. Here, we review recent advances in our understanding of interdependencies amongst circadian rhythms, sleep homeostasis, redox cycles, and other cellular metabolic networks. We speculate that systems-level investigations implementing integrated multi-omics approaches could provide novel mechanistic insights into the connectivity between daily cycles and metabolic systems. PMID- 26866935 TI - Immediate Administration of Intraarticular Triamcinolone Acetonide After Joint Injury Modulates Molecular Outcomes Associated With Early Synovitis. AB - OBJECTIVE: To test whether intraarticular corticosteroid injection mitigates injury-induced synovitis and collagen degradation after anterior cruciate ligament transection (ACLT) and to characterize the synovial response using a functional genomics approach in a preclinical model of posttraumatic osteoarthritis. METHODS: Yorkshire pigs underwent unilateral ACLT without subsequent corticosteroid injection (the ACLT group; n = 6) or ACLT with immediate injection of 20 mg triamcinolone acetonide (the steroid group; n = 6). A control group of pigs (the intact group; n = 6) did not undergo surgery. Total synovial membrane cellularity and synovial fluid concentration of C1,2C neoepitope-bearing collagen fragments 14 days after injury were primary end points and were compared between the ACLT, steroid, and intact groups. Cells were differentiated by histologic phenotype and counted, while RNA sequencing was used to quantify transcriptome-wide gene expression and monocyte, macrophage, and lymphocyte markers. RESULTS: In the intact group, total cellularity was 13% (95% confidence interval [95% CI] 9-16) and the C1,2C concentration was 0.24 MUg/ml (95% CI 0.08-0.39). In the ACLT group, significant increases were observed in total cellularity (to 21% [95% CI 16-27]) and C1,2C concentration (to 0.49 MUg/ml [95% CI 0.39-0.59]). Compared to values in the ACLT group, total cellularity in the steroid group was nonsignificantly decreased to 17% (95% CI 15-18) (P = 0.26) and C1,2C concentration in the steroid group was significantly decreased to 0.29 MUg/ml (95% CI 0.23-0.35) (P = 0.04). A total of 255 protein-coding transcripts were differentially expressed between the ACLT group and the intact group. These genes mainly enriched pathways related to cellular immune response, proteolysis, and angiogenesis. Mononuclear leukocytes were the dominant cell type in cell dense areas. MARCO, SOCS3, CCR1, IL4R, and MMP2 expression was significantly associated with C1,2C levels. CONCLUSION: Early intraarticular immunosuppression mitigated injury-induced increases in collagen fragments, an outcome better predicted by specific marker expression than by histologic measures of synovitis. PMID- 26866936 TI - Interlocked supramolecular glycoconjugated polymers for receptor-targeting theranostics. AB - We report an interlocked supramolecular ensemble formed between a conjugated polymer (CP) and a fluorescent glycoprobe for receptor-targeting cancer cell theranostics. PMID- 26866937 TI - Protective Role of Adipose-Derived Stem Cells in Staphylococcus aureus-Induced Lung Injury is Mediated by RegIIIgamma Secretion. AB - Effective and specific therapeutic approaches are still needed for treating acute lung injury caused by severe pneumonia. Adipose-derived stem cells (ADSCs) are well-characterized adult stem cells that have antibacterial and anti-inflammatory effects. In this study, we evaluated the therapeutic effect of ADSCs on Staphylococcus aureus-induced acute lung injury in mice. Our results showed that intratracheal injection of ADSCs could attenuate the severity of lung inflammation, and reduce the bacterial load as well as mortality among infected mice. Our experiments also revealed that the secretion of regenerating islet derived IIIgamma (RegIIIgamma) is responsible for the protective effect of ADSCs. Moreover, the expression of RegIIIgamma requires TLR2, MyD88, and JAK2/STAT3 activation. In conclusion, ADSCs exhibit a direct antimicrobial activity that is mediated primarily by the TLR2-MyD88-JAK2/STAT3-dependent secretion of RegIIIgamma. Stem Cells 2016;34:1947-1956. PMID- 26866938 TI - Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells. AB - Redox regulation in cancer stem cells (CSCs) is viewed as a good target for cancer therapy because redox status plays an important role in cancer stem-cell maintenance. Here, we investigated the role of Peroxiredoxin II (Prx II), an antioxidant enzyme, in association with maintenance of liver CSCs. Our study demonstrates that Prx II overexpressed in liver cancer cells has high potential for self-renewal activity. Prx II expression significantly corelated with expression of epithelial-cell adhesion molecules (EpCAM) and cytokerain 19 in liver cancer tissues of hepatocellular carcinoma (HCC) patients. Downregulation of Prx II in Huh7 cells with treatment of siRNA reduced expression of EpCAM and CD133 as well as Sox2 in accordance with increased ROS and apoptosis, which were reversed in Huh7-hPrx II cells. Huh7-hPrx II cells exhibited strong sphere formation activity compared with mock cells. Vascular endothelial growth factor (VEGF) exposure enhanced sphere formation, cell-surface expression of EpCAM and CD133, and pSTAT3 along with activation of VEGF receptor 2 in Huh7-hPrx II cells. The result also emerged in Huh7-H-ras(G12V) and SK-HEP-1-H-ras(G12V) cells with high-level expression of Prx II. Prx II was involved in regulation of VEGF driving cancer stem cells through VEGFR-2/STAT3 signaling to upregulate Bmi1 and Sox2. In addition, knockdown of Prx II in Huh7-H-ras(G12V) cells showed significant reduction in cell migration in vitro and in tumorigenic potential in vivo. Taken together, all the results demonstrated that Prx II plays a key role in the CSC self-renewal of HCC cells through redox regulation. Stem Cells 2016;34:1188-1197. PMID- 26866939 TI - Large Deformation Mechanisms, Plasticity, and Failure of an Individual Collagen Fibril With Different Mineral Content. AB - Mineralized collagen fibrils are composed of tropocollagen molecules and mineral crystals derived from hydroxyapatite to form a composite material that combines optimal properties of both constituents and exhibits incredible strength and toughness. Their complex hierarchical structure allows collagen fibrils to sustain large deformation without breaking. In this study, we report a mesoscale model of a single mineralized collagen fibril using a bottom-up approach. By conserving the three-dimensional structure and the entanglement of the molecules, we were able to construct finite-size fibril models that allowed us to explore the deformation mechanisms which govern their mechanical behavior under large deformation. We investigated the tensile behavior of a single collagen fibril with various intrafibrillar mineral content and found that a mineralized collagen fibril can present up to five different deformation mechanisms to dissipate energy. These mechanisms include molecular uncoiling, molecular stretching, mineral/collagen sliding, molecular slippage, and crystal dissociation. By multiplying its sources of energy dissipation and deformation mechanisms, a collagen fibril can reach impressive strength and toughness. Adding mineral into the collagen fibril can increase its strength up to 10 times and its toughness up to 35 times. Combining crosslinks with mineral makes the fibril stiffer but more brittle. We also found that a mineralized fibril reaches its maximum toughness to density and strength to density ratios for a mineral density of around 30%. This result, in good agreement with experimental observations, attests that bone tissue is optimized mechanically to remain lightweight but maintain strength and toughness. PMID- 26866940 TI - Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis. AB - OBJECTIVE: In patients with osteoarthritis (OA), bone marrow lesions (BMLs) are intimately linked to disease progression. We hypothesized that aberrant multipotential stromal cell (also known as mesenchymal stem cell [MSC]) responses within bone tissue contributes to BML pathophysiology. The aim of this study was to investigate BML and non-BML native subchondral bone MSCs for numeric, topographic, in vitro functional, and gene expression differences. METHODS: Ex vivo 3T magnetic resonance imaging (MRI) of the femoral heads of 20 patients with hip OA was performed. MRI-determined BML and non-BML regions were excised and enzymatically treated to extract cells and quantify MSCs using flow cytometry and colony-forming unit-fibroblast (CFU-F) assay. Immunohistochemical analysis was performed to determine in vivo CD271+ MSC distribution. Culture-expanded CD271+ cells were analyzed for tripotentiality and gene expression. RESULTS: BML regions were associated with greater trabecular bone area and cartilage damage compared with non-BML regions. The proportion of CD45-CD271+ MSCs was higher in BML regions compared with non-BML regions (median difference 5.6-fold; P < 0.001); the CFU-F assay showed a similar trend (median difference 4.3-fold; P = 0.013). Immunohistochemistry revealed CD271+ cell accumulation in bone adjacent to cartilage defects and areas of osteochondral angiogenesis. BML MSCs had lower proliferation and mineralization capacities in vitro and altered expression of TNFSF11/RANKL and CXCR4/stromal cell-derived factor 1 receptor. OA MSCs showed up regulated transcripts for CXCR1 and CCR6 compared with MSCs derived from healthy or osteoporotic bone. CONCLUSION: This study is the first to show numeric and topographic alterations in native MSCs in the diseased bone of patients with hip OA. Given the associated functional perturbation of MSCs, these data suggest that subchondral bone MSC manipulation may be an OA treatment target. PMID- 26866942 TI - Notes from the Field: Circulating Vaccine-Derived Poliovirus Outbreaks - Five Countries, 2014-2015. AB - In 2015, wild poliovirus (WPV) transmission was identified in only Afghanistan and Pakistan (1). The widespread use of live, attenuated oral poliovirus vaccine (OPV) has been key in polio eradication efforts. However, OPV use, particularly in areas with low vaccination coverage, is associated with the low risk for emergence of vaccine-derived polioviruses (VDPV), which can cause paralysis (2). VDPVs vary genetically from vaccine viruses and can cause outbreaks in areas with low vaccination coverage. Circulating VDPVs (cVDPVs) are VDPVs in confirmed outbreaks. Single VDPVs for which the origin cannot be determined are classified as ambiguous (aVDPVs), which can also cause paralysis. Among the three types of WPV, type 2 has been declared to be eradicated. More than 90% of cVDPV cases have been caused by type 2 cVDPVs (cVDPV2). Therefore, in April 2016, all OPV-using countries of the world are discontinuing use of type 2 Sabin vaccine by simultaneously switching from trivalent OPV (types 1, 2, and 3) to bivalent OPV (types 1 and 3) for routine and supplementary immunization. The World Health Organization recently broadened the definition of cVDPVs to include any VDPV with genetic evidence of prolonged transmission (i.e., >1.5 years) and indicated that any single VDPV2 event (a case of paralysis caused by a VDPV or isolation of a VDPV from an environmental specimen) should elicit a detailed outbreak investigation and local immunization response. A confirmed cVDPV2 detection should elicit a full poliovirus outbreak response that includes multiple supplemental immunization activities (SIAs); an aVDPV designation should be made only after investigation and response (3). Since 2005, there have been 1-8 cVDPV outbreaks and 3-12 aVDPV events per year. There are currently five active cVDPV outbreaks in Guinea, Laos, Madagascar, Myanmar, and Ukraine, and four other active VDPV events. PMID- 26866941 TI - A comprehensive meta-analysis of ZNF804A SNPs in the risk of schizophrenia among Asian populations. AB - Common variants in ZNF804A increased the risk of schizophrenia (and bipolar disorder), with low effect sizes in Europeans, which is in line with the polygenic nature of the illnesses, and implies that genetic analyses in small samples may not be sufficient to detect stable results. This notion is supported by the inconsistent replications of ZNF804A variations among individual small Asian samples, indicating the absence of definitive conclusions in this population. We collected psychiatric phenotypic and genetic data from Asian genome-wide association (GWA) and individual replication studies, which include up to 13,452 cases, 17,826 healthy controls, and 680 families, that is, the largest-scale study on ZNF804A in Asian populations to date. The European GWAS risk single nucleotide polymorphism (SNP) rs1344706 was nominally associated with schizophrenia in these Asian samples (one-tailed P = 4.26 * 10(-2) , odds ratio [OR] = 1.048), and the association was further strengthened when bipolar disorder data was also included (one-tailed P = 1.85 * 10(-2) , OR = 1.057). Besides, a non-synonymous SNP rs1366842 in the exon 4 of ZNF804A was also associated with schizophrenia (P = 9.96 * 10(-3) , OR = 1.095). We additionally analyzed other 163 SNPs covering ZNF804A region, but none of them showed any evidence of association. Though the two SNPs did not remain significant if we applied multiple corrections, our analysis should be interpreted as a primary replication study with in prior hypothesis, and rs1344706 and rs1366842 might confer a small but detectable risk of schizophrenia (and bipolar disorder) in Asians. Moreover, the current data suggest the necessity of replication analyses in a large enough scale samples. PMID- 26866943 TI - So You Are Published, but Are You Read? PMID- 26866946 TI - Erratum, Vol. 13, January 14 Release. AB - This corrects the article DOI: 10.5888/pcd12.150491. PMID- 26866945 TI - Examining the interaction of parental involvement and parenting style in predicting adherence in youth with type 1 diabetes. AB - INTRODUCTION: This study examined whether aspects of parenting style (specifically, warmth, autonomy support, and coercion) moderated the association between parental involvement and adherence in youth with type 1 diabetes. METHODS: Children ages 8 to 16 years with type 1 diabetes and a parent completed assessments of parental involvement, parenting style, and adherence. RESULTS: Parent autonomy support and coercion were associated with adherence but warmth was not. Child report of more parental involvement was associated with better adherence. Warmth, autonomy support, and coercion were not moderators. DISCUSSION: The findings underscore the importance of parental involvement, operationalized as responsibility for diabetes tasks, and parenting style, specifically coercion and autonomy support, for adherence in pediatric chronic illness management. Longitudinal research is needed to better understand how and why dimensions of involvement (e.g., responsibility, monitoring, support) vary over time and whether they impact outcomes differentially. PMID- 26866947 TI - Food Security Status and Barriers to Fruit and Vegetable Consumption in Two Economically Deprived Communities of Oakland, California, 2013-2014. AB - INTRODUCTION: Food security status may moderate how people perceive barriers to fruit and vegetable consumption. This study aimed to 1) describe the association between fruit and vegetable consumption and microbarriers and mezzobarriers to consumption, and 2) test whether these associations differ by food security status. METHODS: We surveyed adults (n = 531) living in 2 economically deprived communities in Oakland, California, in 2013 and 2014. Multivariate linear regression assessed associations between microbarriers (taste, cost, busyness) and mezzobarriers (produce selection, quality, and purchase ease) and fruit and vegetable consumption, derived from a 26-item dietary screener. Interactions were tested by food security status. RESULTS: Respondents consumed a mean 2.4 (standard deviation, 1.5) servings of fruits and vegetables daily; 39% of the sample was food insecure. Being too busy to prepare healthy foods was associated with reduced fruit and vegetable consumption (beta(busyness) = -0.40; 95% confidence interval [CI], -0.52 to -0.28) among all respondents. Food security moderated the relationship between fruit and vegetable consumption and taste, cost, and perceived ease of purchase of healthy foods. Among the food secure, disliking healthy food taste (beta(taste) = -0.38; 95% CI, -0.60 to -0.15) and cost (beta(cost) = -0.29; 95% CI, -0.44 to -0.15) concerns were associated with lower consumptions of fruits and vegetables. Mezzobarriers were not significantly associated with consumption in either group. CONCLUSION: Perceived time constraints influenced fruit and vegetable consumption. Taste and cost influenced fruit and vegetable consumption among the food secure and may need to be considered when interpreting analyses that describe dietary intake and designing diet-related interventions. PMID- 26866948 TI - Dyslipidemia and Food Security in Low-Income US Adolescents: National Health and Nutrition Examination Survey, 2003-2010. AB - INTRODUCTION: Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents. METHODS: We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. We used logistic regression to examine the relationship between household food security status and the odds of having abnormalities with fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, and apolipoprotein B (Apo B). Models included age, sex, race/ethnicity, smoking status, partnered status in the household, and maternal education, with additional adjustment for adiposity. RESULTS: Household food security status was not associated with elevated TC or LDL-C. Adolescents with marginal food security were more likely than food-secure peers to have elevated TGs (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.14-3.05), TG/HDL-C ratio (OR = 1.74; 95% CI, 1.11-2.82), and Apo B (OR = 1.98; 95% CI, 1.17-3.36). Female adolescents with marginal food security had greater odds than male adolescents of having low HDL-C (OR = 2.69; 95% CI, 1.14-6.37). No elevated odds of dyslipidemia were found for adolescents with low or very low food security. Adjustment for adiposity did not attenuate estimates. CONCLUSION: In this nationally representative sample, low-income adolescents living in households with marginal food security had increased odds of having a pattern consistent with atherogenic dyslipidemia, which represents a cardiometabolic burden above their risk from adiposity alone. PMID- 26866950 TI - Edge morphology evolution of graphene domains during chemical vapor deposition cooling revealed through hydrogen etching. AB - During cooling, considerable changes such as wrinkle formation and edge passivation occur in graphene synthesized on the Cu substrate. Wrinkle formation is caused by the difference in the thermal expansion coefficients of graphene and its substrate. This work emphasizes the cooling-induced edge passivation. The graphene-edge passivation can limit the regrowth of graphene at the domain edge. Our work shows that silicon-containing particles tend to accumulate at the graphene edge, and the formation of these particles is related to cooling. Furthermore, a clear curvature can be observed at the graphene edge on the Cu substrate, indicating the sinking of the graphene edge into the Cu substrate. Both the sinking of the graphene edge and the accumulation of silicon-containing particles are responsible for edge passivation. In addition, two kinds of graphene edge morphologies are observed after etching, which were explained by different etching mechanisms that illustrate the changes of the graphene edge during cooling. PMID- 26866949 TI - A Brief Evaluation of a Project to Engage American Indian Young People as Agents of Change in Health Promotion Through Radio Programming, Arizona, 2009-2013. AB - Young people can be valuable motivational resources for health promotion. A project implemented from 2009 through 2013 in a small American Indian community in northwest Arizona recruited American Indian young people aged 10 to 21 as agents of change for health promotion through radio programming. Thirty-seven participants were recruited and trained in broadcasting and creative writing techniques; they produced and aired 3 radio dramas. In post-project evaluation, participants were confident they could influence community behaviors but thought that training techniques were too similar to those used in school activities and thus reduced their drive to engage. Effective engagement of young people requires creativity to enhance recruitment, retention, and impact. PMID- 26866951 TI - Letter: De Novo Arteriovenous Malformation Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain. PMID- 26866952 TI - In Reply: De Novo Arteriovenous Malformation Growth Secondary to Implantation of Genetically Modified Allogeneic Mesenchymal Stem Cells in the Brain. PMID- 26866953 TI - Recent approaches to evaluating and monitoring geographic atrophy. AB - PURPOSE OF REVIEW: Given the increasing prevalence of geographic atrophy from age related macular degeneration as the number of individuals over 85 increases throughout the world, as well as the recent increase in potential treatments to slow growth of geographic atrophy, this article discusses recent findings regarding retinal imaging of geographic atrophy to detect its presence or expansion over time. RECENT FINDINGS: During the review period, the COMPLETE (Systemic complement inhibition with eculizumab for geographic atrophy in age related macular degeneration) and the GATE (Randomized trial to evaluate tandospirone in geographic atrophy secondary to age-related macular degeneration) studies, respectively, reported no beneficial effects of intravenous eculizumab or tandospirone eye drops, respectively, identified on the growth of geographic atrophy. Several imaging and visual function studies have evaluated the role of various techniques using fundus autofluorescence, optical coherence tomography, microperimetry, or other investigator-initiated tools to assess geographic atrophy growth or progression over time, although the ideal imaging for geographic atrophy remains unknown. Some predictive factors for geographic atrophy growth recently suggested include genetic features, geographic atrophy characteristics in the fellow eye, or the presence of outer retinal tubulation on optical coherence tomography. SUMMARY: Quantification of geographic atrophy is important for evaluating growth of geographic atrophy. Numerous new imaging techniques of geographic atrophy beyond human grading of fundus photographs or fluorescein angiograms have emerged, but the ideal imaging for geographic atrophy has yet to be determined. PMID- 26866954 TI - Bone Mineral Density Changes Among Young, Healthy African Women Receiving Oral Tenofovir for HIV Preexposure Prophylaxis. AB - BACKGROUND: Limited data exist on effect of tenofovir disoproxil fumarate (TDF) when used for preexposure prophylaxis (PrEP) on bone mineral density (BMD) in HIV negative women. We evaluated the effect of daily oral TDF and emtricitabine/TDF compared with placebo on BMD among women enrolled in an HIV-1 PrEP trial. METHODS: HIV-uninfected women in Uganda and Zimbabwe had BMD measurements of lumbar spine (LS) and total hip (TH) by dual-energy x-ray absorptiometry at baseline and every 24 weeks for 48 weeks of active treatment and for 48 weeks after discontinuation of study medication. Plasma tenofovir levels were assessed every 12 weeks for the first 48 weeks. RESULTS: Of 518 women enrolled, 432 had dual-energy x-ray absorptiometry results at baseline and week 48. In the primary analysis, no significant differences in percent BMD change in hip or spine between arms observed, likely because of low product adherence. Among the subset with tenofovir detection in 75%-100% of plasma samples, the mean percent BMD change from baseline to week 48 in the LS was 1.4% lower for TDF or emtricitabine/TDF recipients than for placebo (P = 0.002) and TH BMD was 0.9% lower (P = 0.018). BMD changes from end of active treatment to 48 weeks were significantly greater in the active arm participants compared with placebo participants with a net difference of approximately +0.9% at the LS (P = 0.007) and +0.7% (P = 0.003) at the TH. CONCLUSIONS: TDF-containing oral PrEP resulted in small but significant reversible decreases in hip and spine BMD among young African women. PMID- 26866956 TI - Scanner-Based Protocol-Driven Ultrasound: An Effective Method to Improve Efficiency in an Ultrasound Department. AB - OBJECTIVE: For ultrasound, a wide variation is often observed among the number and sequence of images acquired for a particular examination type. Scanner-based protocols are preset pathways in the ultrasound machine that guide a sonographer through the required study images. These protocols can streamline image acquisition by improving consistency and efficiency of ultrasound examinations. This study evaluated whether implementation of scanner-based protocol-driven ultrasound improves efficiency by decreasing the scanning duration and number of images acquired. MATERIALS AND METHODS: Retrospective evaluation of 437 carotid Doppler examinations, 395 complete abdominal ultrasound examinations with Doppler imaging, and 413 bilateral lower extremity venous Doppler examinations for deep venous thrombosis (DVT) performed by five sonographers before and after implementation of scanner-based protocol-driven ultrasound was performed. The scanning duration and number of images acquired for each study were recorded. Statistical analysis compared the scanning duration and number of images acquired before and after implementation of protocol-driven ultrasound. A p value of < 0.05 was considered significant. RESULTS: A significant decrease in scanning duration occurred for both carotid Doppler ultrasound examinations (decrease by 12.4% [2.7 minutes], p < 0.0001) and complete abdominal ultrasound examinations with Doppler imaging (decrease by 7.5% [2.0 minutes], p = 0.0054) after implementation of protocol-driven ultrasound. The decrease in scanning duration was not significant for lower extremity DVT Doppler examinations (p = 0.4192). In addition, there was a significant decrease in the overall number of images obtained for all three types of studies. CONCLUSION: Scanner-based protocol driven ultrasound is an effective method that streamlines image acquisition and significantly improves efficiency in an ultrasound department while ensuring consistency and adherence to accreditation guidelines. PMID- 26866955 TI - Implementation and Operational Research: Computer-Assisted Intervention for Safer Sex in HIV-Positive Men Having Sex With Men: Findings of a European Randomized Multi-Center Trial. AB - OBJECTIVE: Men who have sex with men (MSM) are the key population most affected by HIV in Europe. We performed the first European multicenter, simple-randomized parallel-group study to test the effectiveness of a theory-guided computer assisted intervention to improve safer sex among HIV-positive men who have sex with men. METHODS: Between February, 2011 and February, 2013, 112 participants were enrolled in 8 different European HIV-care settings. Intervention participants received 3 individual counseling sessions facilitated by trained service providers using computer-assisted tools. The control-group received sexual health advice delivered as part of regular HIV care. Outcome behavior (self-reported condom use at last intercourse; combined HIV transmission risk score), its influencing factors, and mediating variables were assessed at baseline, and at 3 and 6 months follow-up. Mixed effects models were used to compare primary outcomes (condom use at last intercourse, HIV transmission risk score), and mediation analysis to explore intervention effects. RESULTS: Condom use at last intercourse increased more among intervention than control participants at 3 months follow-up (odds ratio of 3.83; P = 0.03), but not significantly at 6 months follow-up. Intervention participants reported a lower transmission risk at 3 months follow-up than controls (odds ratio compared with baseline of 11.53 and 1.28, respectively; P = 0.008), but this effect became nonsignificant at 6 months. Intervention effects were mediated by the proximal variables, self-efficacy to negotiate condom use and condom attitudes. CONCLUSIONS: This intervention showed short-term effectiveness. The intervention should be replicated in other settings, eventually investigating if booster counseling sessions would yield a longer lasting effect. PMID- 26866957 TI - Prevalence and Incidence of Osteoporosis and Osteoporotic Vertebral Fracture in Korea: Nationwide Epidemiological Study Focusing on Differences in Socioeconomic Status. AB - STUDY DESIGN: A cross-national study. OBJECTIVE: To determine the prevalence and incidence of osteoporosis (OP) and osteoporotic vertebral fracture (OVF) in Korea and to investigate if socioeconomic status has an effect. SUMMARY OF BACKGROUND DATA: As life expectancy increases, OP and related fragility fractures are also increasing. This presents a serious challenge, not only for health authorities but also for individuals, their families, and society overall. Determining the prevalence and incidence of OP and related fragility fractures is the first step in developing strategies to reduce their increasing disease burdens. Concurrently, we need to confirm whether people with low socioeconomic status are more susceptible to these diseases. METHODS: Using the Health Insurance Review and Assessment Service (HIRA) database from 2008 to 2012, we estimated the annual prevalence and incidence of OP and OVF and investigated the differences according to socioeconomic status by National Health Insurance (NHI) beneficiaries and Medical Aid (MA) recipients. RESULTS: In 2012, the standardized prevalence of OP in the NHI and MA groups was 3968 and 6927 per 100,000, respectively (odds ratio, 3.83). The standardized incidence of OP in the MA group was significantly higher than in the NHI group in 2011 and 2012 (odds ratios, 2.34 and 2.19, respectively). In addition, the standardized incidence of OVF in the MA group in 2011 and 2012 was 408 and 389 per 100,000, respectively, and the incidence in the MA group was significantly higher than in the NHI group (odds ratios, 4.13 and 4.12, respectively; P < 0.001). CONCLUSION: We confirmed that the prevalence and incidence of OP and OVF in the MA group were higher than those in the NHI group. It showed that low income might be a significant factor related to OP and OVF. LEVEL OF EVIDENCE: 3. PMID- 26866958 TI - Clinical Q & A: Translating Therapeutic Temperature Management from Theory to Practice. PMID- 26866962 TI - Enhanced UV-visible response of bismuth subcarbonate nanowires for degradation of xanthate and photocatalytic reaction mechanism. AB - (BiO)2CO3 nanowires were prepared by simple hydrothermal treatment of commercial Bi2O3 powders and characterized by X-ray diffractometry, scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, and X ray photoelectron spectroscopy (XPS). The photocatalytic activity of (BiO)2CO3 nanowires was studied through degradation of sodium isopropyl xanthate. Photocatalytic experimental results indicated that the as-prepared (BiO)2CO3 nanowires show high photocatalytic efficiency. Photocatalytic activity increased after two cycles. Time-dependent UV-vis spectra demonstrated that the final degradation products included isopropyl alcohol and carbon disulfide. UV-vis diffuse reflection spectra showed that the band gap of the as-prepared (BiO)2CO3 nanowires and recycled (BiO)2CO3 nanowires were 2.75 eV and 1.15 eV, respectively. XPS results indicated that formation of Bi2S3@(BiO)2CO3 core-shell nanowires occurred after recycled photodegradation of isopropyl xanthate owing to existence of two types of Bi configurations in the recycled (BiO)2CO3 nanowires. A probable degradation mechanism of isopropyl xanthate was also proposed. PMID- 26866963 TI - Biochar filters reduced the toxic effects of nickel on tomato (Lycopersicon esculentum L.) grown in nutrient film technique hydroponic system. AB - This work used the nutrient film technique to evaluate the role of biochar filtration in reducing the toxic effects of nickel (Ni(2+)) on tomato growth. Three hydroponic treatments: T1 (control), T2 (with Ni(2+)), and T3 (with Ni(2+) and biochar) were used in the experiments. Scanning electron microscopy equipped with energy dispersive X-ray spectroscopy and Fourier transform spectroscopy was used to characterize the pre- and post-treatment biochar samples. The results illustrated that precipitation, ion exchange, and complexation with surface functional groups were the potential mechanisms of Ni(2+) removal by biochar. In comparison to the control, the T2 treatment showed severe Ni-stress with alterations in cell wall structure, distortions in cell nucleus, disturbances in mitochondrial system, malformations in stomatal structure, and abnormalities in chloroplast structure. The biochar filters in T3 treatment reduced dysfunctions of cell organelles in root and shoot cells. Total chlorophyll concentration decreased by 41.6% in T2 treatment. This reduction, however, was only 20.8% due to the protective effect of the biochar filters. The presence of Ni(2+) in the systems reduced the tomato fruit yield 58.5% and 31.9% in T2 and T3, respectively. Nickel concentrations reached the toxic limit in roots, shoots, and fruits in T2, which were not observed in T3. Biochar filters in T3 also minimized the dramatic reductions in nutrients concentration in roots, shoots, and fruits, which occurred in T2 treatment due to the severe Ni-stress. Findings from this work suggested that biochar filters can be used on farms as a safeguard for wastewater irrigation. PMID- 26866964 TI - Stabilization of cationic and anionic metal species in contaminated soils using sludge-derived biochar. AB - Currently, sludge pyrolysis has been considered as a promising technology to solve disposal problem of municipal sewage sludge, recover sludge heating value, sequester carbon and replenish nutrients in farmland soils. The resultant sludge derived biochar (SDBC) is potentially an excellent stabilizing agent for metal species. This study applied the SDBC into four soils that had been contaminated in field with cationic Pb(II) and Cd(II)/Ni(II), and anionic Cr(VI) and As(III), respectively. The performance of metal stabilization under various operational and environmental conditions was evaluated with acid batch extraction and column leaching tests. Results indicated the SDBC could effectively stabilize these metals, which was favored by elevated temperature and longer aging. Periodic temperature decrease from 45 to 4 degrees C resulted in the release of immobilized Cr(VI) and As(III) but not Pb(II). However, a longer aging time offset such metal remobilization. This was possibly because more Pb was strongly bound and even formed stable precipitates, as shown by XRD and sequential extraction results. With increasing time, Cr(VI) was sorbed and partly reduced to Cr(III), while immobilized As(III) was co-oxidized to As(V) as indicated by XPS spectra. Column tests revealed that adding SDBC as a separate layer was unfavorable because the concentrated Cd(II) and Ni(II) in localized positions increased the peak levels of metal release under continuous acid leaching. In contrast, uniformly mixed SDBC could effectively delay the metal breakthrough and reduce their released amounts. Yet, a long-term monitoring may be required for evaluating the potential leaching risks and bioavailability/toxicity of these immobilized and transformed species in the SDBC-amended soils. PMID- 26866965 TI - Sorption of diclofenac and naproxen onto MWCNT in model wastewater treated by H2O2 and/or UV. AB - The application of oxidation processes such as UV and/or H2O2 will change the physicochemical properties of carbon nanotubes (CNT). It may affect the sorption affinity of CNT to different contaminants and then affect their fate in the environment. In the present study the adsorption of two very common used pharmaceuticals (diclofenac and naproxen) onto CNT treated by UV, H2O2 or UV/H2O2 was investigated. Four different adsorption models (Freundlich, Langmuir, Temkin, Dubinin-Radushkevich) were tested. The best fitting of experimental data was observed for Freundlich or Langmuir model. The significant relationships between Q calculated from Langmuir model with O% and dispersity were observed. Kinetics of diclofenac and naproxen followed mainly pseudo-second order indicating for chemisorption limiting step of adsorption. The data showed that the mechanism of sorption was physical or chemical depending on the type of CNT modification. PMID- 26866966 TI - Element mobilization from Bakken shales as a function of water chemistry. AB - Waters that return to the surface after injection of a hydraulic fracturing fluid for gas and oil production contain elements, including regulated metals and metalloids, which are mobilized through interactions between the fracturing fluid and the shale formation. The rate and extent of mobilization depends on the geochemistry of the formation and the chemical characteristics of the fracturing fluid. In this work, laboratory scale experiments investigated the influence of water chemistry on element mobilization from core samples taken from the Bakken formation, one of the most productive shale oil plays in the US. Fluid properties were systematically varied and evaluated with regard to pH, oxidant level, solid:water ratio, temperature, and chemical additives. Element mobilization strongly depended on solution pH and redox conditions and to a lesser extent on the temperature and solid:water ratio. The presence of oxygen and addition of hydrogen peroxide or ammonium persulfate led to pyrite oxidation, resulting in elevated sulfate concentrations. Further, depending on the mineral carbonates available to buffer the system pH, pyrite oxidation could lower the system pH and enhance the mobility of several metals and metalloids. PMID- 26866967 TI - Synthesis and biological evaluation of D-ring fused 1,2,3-thiadiazole dehydroepiandrosterone derivatives as antitumor agents. AB - A series of D-ring fused 1,2,3-thiadiazole DHEA derivatives were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. It is amazing that for these compounds, T47D cell line was much more sensitive than other tumor cell lines. The most potent saturated N-heterocyclic derivatives showed similar antitumor effect with the positive control compound ADM (adriamycin) on T47D cells, that was 44-60 folds more potent than the lead compound DHEA. Most compounds with potent antitumor activity displayed low toxicity on normal human fibroblasts (HAF). Especially compound 25 (CH33) showed an IC50 of 0.058 MUM on T47D cells and its selectivity index (SI) between HAF and T47D was 364, which was 214 folds better than ADM (SI = 1.7). The apoptosis, colony formation and transwell migration assays of 25 were performed on T47D cell line. The primary mechanism study showed that 25 caused a dose-dependent induction of apoptosis, and induced phosphorylation of EphA2 and EphB3 in T47D cells. The in vivo antitumor effect of 25 was also observed in T47D tumor-bearing mice without obvious toxicity. PMID- 26866968 TI - Potent alpha-amino-beta-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies. AB - 4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the beta-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation. PMID- 26866969 TI - Cocaine cues retain silent traces of an excitatory history after conversion into conditioned inhibitors: 'the ghost in the addict'. AB - The present experiment investigated the extent to which the A+/AB- conditioned inhibition procedure could counteract an excitatory drug-related conditioning history. In two groups of rats, a light stimulus was established as a signal for the absence of cocaine. For the History group, the light had previously been a discriminative stimulus (S) that occasioned cocaine self-administration and could thus be classified as a cocaine excitor. In comparison, the No-History group first encountered the light during conditioned inhibition training. During conditioned inhibition training, both groups self-administered cocaine during tone as well as during click Ss, whereas drug seeking was eliminated in click plus-light, wherein cocaine was not available (A+/AB-). Drug seeking was essentially eliminated in both groups. Nevertheless, on a summation test the light reduced cocaine seeking occasioned by the tone S by 95% in the No-History group, but by less than 50% in the History group. This summation test result showed that the effects of a drug-related history persisted even after the light was converted into an effective conditioned inhibitor on the training baseline through the powerful A+/AB- procedure. Future research should seek procedures that produce even stronger conditioned inhibition that eliminates such residual 'silent' drug excitation, the 'ghost in the addict'. PMID- 26866970 TI - The ketamine analogue methoxetamine generalizes to ketamine discriminative stimulus in rats. AB - Methoxetamine (MXE) is a chemical analogue of ketamine. Originally proposed as a ketamine-like fast-acting antidepressant, owing to similar N-methyl-D-aspartate blocker properties, it is now scheduled for reports of hallucinations and psychosis similar to ketamine and lysergic acid. As little is known about the addictive properties of MXE, the aim of this study was to investigate the similarity between discriminative stimuli of MXE and ketamine, as well as to provide data and protocols that could be used in the future for the characterization of novel ketamine-like drugs. The paradigm used was a two-lever operant conditioning paradigm in which rats were trained to discriminate ketamine (7.5 mg/kg/ml, intraperitoneal) from vehicle. Generalization tests were performed with MXE (0.0625, 0.125, 0.25, 0.5, or 1.0). We also tested the N-methyl-D aspartate channel blocker MK-801 (0.005-0.1), lysergic acid (0.025-0.30), a serotonergic drug that had similar hallucinogenic effects as ketamine and methamphetamine (0.15-0.60) a drug with no generalization with ketamine, injected intraperitoneally presession (mg/kg). MXE and MK-801 fully generalized to ketamine. Lysergic acid and methamphetamine partially substituted for the ketamine stimulus, although the highest lysergic acid dose showed a 77.7% generalization. The present findings suggest that investigation of 'ketamine-like compounds' should explore not only substances with chemical analogy and common molecular mechanisms with ketamine, but also with similar psychopharmacological effects. PMID- 26866971 TI - Dose and elasticity of demand for self-administered cocaine in rats. AB - The present experiment tested whether the elasticity of demand for self administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine - 0.11, 0.33, and 1.0 mg/kg/infusion - on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves. PMID- 26866972 TI - How cognitive biases can distort environmental statistics: introducing the rough estimation task. AB - The purpose of this study was to develop a novel behavioural method to explore cognitive biases. The task, called the Rough Estimation Task, simply involves presenting participants with a list of words that can be in one of three categories: appetitive words (e.g. alcohol, food, etc.), neutral related words (e.g. musical instruments) and neutral unrelated words. Participants read the words and are then asked to state estimates for the percentage of words in each category. Individual differences in the propensity to overestimate the proportion of appetitive stimuli (alcohol-related or food-related words) in a word list were associated with behavioural measures (i.e. alcohol consumption, hazardous drinking, BMI, external eating and restrained eating, respectively), thereby providing evidence for the validity of the task. The task was also found to be associated with an eye-tracking attentional bias measure. The Rough Estimation Task is motivated in relation to intuitions with regard to both the behaviour of interest and the theory of cognitive biases in substance use. PMID- 26866973 TI - Cocaine-like discriminative stimulus effects of phendimetrazine and phenmetrazine in rats. AB - Phendimetrazine is a clinically available anorectic and candidate medication for the treatment of cocaine addiction. Phendimetrazine can be metabolized to the amphetamine-like monoamine releaser phenmetrazine, but it is unclear if phendimetrazine functions as an inactive prodrug or might have activity on its own. As one method to address this issue, the present study compared the potency and time course of phendimetrazine and phenmetrazine to produce cocaine-like discriminative stimulus effects in adult, male rats (N=5) trained to discriminate cocaine (5.6 mg/kg, intraperitoneally) from saline in a two-key food-reinforced discrimination procedure. We hypothesized that, if metabolism to phenmetrazine was required for phendimetrazine effects, then phendimetrazine would be less potent and have a slower onset and offset of effects than phenmetrazine. Both phendimetrazine and phenmetrazine produced dose-dependent cocaine-like discriminative stimulus effects, and phendimetrazine was 7.8-fold less potent than phenmetrazine. However, the time courses of discriminative stimulus effects produced by phendimetrazine and phenmetrazine were similar, with peak effects at 10 min and offset by 100 min. These results show the effectiveness of phendimetrazine to rapidly produce cocaine-like behavioral effects in rats and support other nonhuman primate evidence to suggest that metabolism to phenmetrazine may not be required for phendimetrazine effects. PMID- 26866974 TI - Diacylglycerol pyrophosphate binds and inhibits the glyceraldehyde-3-phosphate dehydrogenase in barley aleurone. AB - The aleurona cell is a model that allows the study of the antagonistic effect of gibberellic acid (GA) and abscisic acid (ABA). Previous results of our laboratory demonstrated the involvement of phospholipids during the response to ABA and GA. ABA modulates the levels of diacylglycerol, phosphatidic acid and diacylglycerol pyrophosphate (DAG, PA, DGPP) through the activities of phosphatidate phosphatases, phospholipase D, diacylglycerol kinase and phosphatidate kinase (PAP, PLD, DGK and PAK). PA and DGPP are key phospholipids in the response to ABA, since both are capable of modifying the hydrolitic activity of the aleurona. Nevertheless, little is known about the mechanism of action of these phospholipids during the ABA signal. DGPP is an anionic phospholipid with a pyrophosphate group attached to diacylglycerol. The ionization of the pyrophosphate group may be important to allow electrostatic interactions between DGPP and proteins. To understand how DGPP mediates cell functions in barley aleurone, we used a DGPP affinity membrane assay to isolate DGPP-binding proteins from Hordeum vulgare, followed by mass spectrometric sequencing. A cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12) was identified for being bound to DGPP. To validate our method, the relatively abundant GAPDH was characterized with respect to its lipid-binding properties, by fat western blot. GAPDH antibody interacts with proteins that only bind to DGPP and PA. We also observed that ABA treatment increased GAPDH abundance and enzyme activity. The presence of phospholipids during GAPDH reaction modulated the GAPDH activity in ABA treated aleurone. These data suggest that DGPP binds to GAPDH and this DGPP and GAPDH interaction provides new evidences in the study of DGPP-mediated ABA responses in barley aleurone. PMID- 26866975 TI - Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates. AB - BACKGROUND: The enzyme, Glucose-6-phosphate dehydrogenase (G6PD), deficiency leads to impaired production of reduced glutathione and predisposes the red cells to be damaged by oxidative metabolites, causing hemolysis. Deficient neonates may manifest clinically as hyperbilirubinemia or even kernicterus. OBJECTIVE: This study was carried out to detect erythrocyte G6PD deficiency in neonatal hyperbilirubinemia. METHODS AND DESIGN: To determine the frequency and effect of G6PD deficiency, this study was conducted on 202 neonates with indirect hyperbilirubinemia. All term and preterm babies up to 13 day of age admitted with clinically evident jaundice were taken for the study. G6PD activity is measured by the UV-Kinetic Method using cellular enzyme determination reagents by spectrophotometry according to manufacturer's instructions. RESULTS: A total of 202 babies were enrolled in this study. Male babies outnumbered the female (71.3% versus 28.7%). Mean age of the study newborns was 3.75 +/- 2.5 days. Eighteen neonates (8.9%) had G6PD deficiency, all are males. One case had combined G6PD deficiency and RH incompatibility. Mean serum total bilirubin was 17.2 +/- 4.4 in G6PD deficient cases. There was significant positive correlation between the time of appearance of jaundice in days and G6PD levels in G6PD deficient cases. CONCLUSION: Neonatal hyperbilirubinemia is associated with various clinical comorbidities. G6PD deficiency is found to one important cause of neonatal jaundice developing on day 2 onwards. PMID- 26866977 TI - Photoredox-Catalyzed Intramolecular Difluoromethylation of N-Benzylacrylamides Coupled with a Dearomatizing Spirocyclization: Access to CF2H-Containing 2 Azaspiro[4.5]deca-6,9-diene-3,8-diones. AB - A visible light-mediated difluoromethylation of N-benzylacrylamides with HCF2SO2Cl as the HCF2 radical precursor is described. The reaction incorporates a tandem cyclization/dearomatization process to afford various difluoromethylated 2 azaspiro[4.5]deca-6,9-diene-3,8-diones bearing adjacent quaternary stereocenters under mild conditions in moderate to excellent yields. PMID- 26866976 TI - Impaired glucose metabolism moderates the course of illness in bipolar disorder. AB - BACKGROUND: The longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population. METHODS: Fifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. RESULTS: Thirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI). LIMITATIONS: Cross-sectional design, small sample size. CONCLUSIONS: Comorbid IGM may be a key moderator of illness progression in BD. PMID- 26866978 TI - Prevalence and Prognostic Impact of Metabolic Syndrome in Asymptomatic (Stage A and B Heart Failure) Patients. AB - BACKGROUND: Metabolic syndrome (MS) has an increased risk of cardiovascular events. Its relationship with asymptomatic left ventricular dysfunction (LVD) and prognosis has not been completely clarified. OBJECTIVES: To determine, in asymptomatic patients (Stage A, B heart failure, HF), whether MS is associated with left ventricular systolic dysfunction (LVSD) and left ventricular diastolic dysfunction and its predictive role for cardiovascular events. MATERIALS AND METHODS: We included 1920 nonconsecutive patients without symptoms of HF, with at least one cardiovascular risk factor, undergoing echocardiographic evaluation as preventive screening. We subdivided the study population according to the presence (Group 1) or absence (Group 2) of MS. The primary endpoint was a composite of cardiac death, myocardial infarction, coronary artery revascularization, stroke, and acute pulmonary edema. Secondary endpoints were hospitalization for HF and HF progression. RESULTS: Overall prevalence of MS was 13.4% (n = 262, Group 1). In Group 2 (n = 1658), the prevalence of LVSD was 12.2%, while the prevalence of LVSD was 21.8% in Group 1 (relative risk [RR] 2.01; 95% confidence interval 1.4-2.8; P < 0.001). Adjusting for age and gender, MS resulted an independent predictor of LVSD (P < 0.001). After a median follow up of 22 months, Group 1 patients had a significantly higher incidence of primary events (P < 0.001), including cardiac death (P = 0.04), and secondary events (P < 0.001). Both primary and secondary endpoints were more frequent in patients with LVSD (P < 0.001). In multivariate survival analysis, MS (but not its specific components) and LVSD were independently associated both with primary and secondary events (P <= 0.003). Incremental chi-square analysis showed the presence of combined LVD added to MS, and age raised significantly the predictive value of the model for the primary endpoint (Incremental chi-square = 8.6). CONCLUSIONS: In stage A and B HF subjects, the coexistence of MS with functional or structural cardiac abnormalities, detected by echocardiography, showed a significant incremental value in predicting clinical cardiovascular events. PMID- 26866979 TI - Effect of dolutegravir functional monotherapy on HIV-1 virological response in integrase strand transfer inhibitor resistant patients. AB - BACKGROUND: VIKING-4 assessed the safety and efficacy of dolutegravir in heavily antiretroviral treatment-experienced patients who had documented integrase strand transfer inhibitor (INSTI) resistance-associated substitutions in their HIV. VIKING-4 had a placebo-controlled 7-day dolutegravir functional monotherapy phase followed by dolutegravir plus an optimized background regimen for 48 weeks. METHODS: Independent resistance analyses evaluated week 48 virological responses in the VIKING-4 trial based on the presence of baseline INSTI resistance associated substitutions and baseline dolutegravir phenotypic susceptibility. Response rates at week 48 based on baseline dolutegravir resistance subgroups were compared for the 7-day dolutegravir functional monotherapy arm and placebo control arm. Additionally, genotypic and phenotypic resistance at day 8 and time of failure was analysed for the virological failures from both arms. RESULTS: Week 48 response rates for VIKING-4 were 23% (3/13) in the 7-day dolutegravir functional monotherapy arm compared with 60% (9/15) in the 7-day placebo arm. Response rates were consistently lower in the dolutegravir functional monotherapy arm across baseline INSTI genotypic and phenotypic subgroups. There was a higher proportion of virological failures in the 7-day dolutegravir functional monotherapy arm (n=6/13; 46%) compared with the 7-day placebo arm (n=3/15; 20%). Additionally, five virological failures in the dolutegravir arm had virus expressing emergent INSTI resistance-associated substitutions compared with two in the placebo arm. CONCLUSIONS: Analysis of response rates and resistance emergence in VIKING-4 suggests careful consideration should be given to the duration of functional monotherapy in future studies of highly treatment experienced patients to reduce the risk of resistance and virological failure. PMID- 26866981 TI - Scrutinizing the Noninnocence of Quinone Ligands in Ruthenium Complexes: Insights from Structural, Electronic, Energy, and Effective Oxidation State Analyses. AB - The most relevant manifestations of ligand noninnocence of quinone and bipyridine derivatives are thoroughly scrutinized and discussed through an extensive and systematic set of octahedral ruthenium complexes, [(en)2RuL](z), in four oxidation states (z = +3, +2, +1, and 0). The characteristic structural deformation of ligands upon coordination/noninnocence is put into context with the underlying electronic structure of the complexes and its change upon reduction. In addition, by means of decomposing the corresponding reductions into electron transfer and structural relaxation subprocesses, the energetic contribution of these structural deformations to the redox energetics is revealed. The change of molecular electron density upon metal- and ligand centered reductions is also visualized and shown to provide novel insights into the corresponding redox processes. Moreover, the charge distribution of the pi subspace is straightforwardly examined and used as indicator of ligand noninnocence in the distinct oxidation states of the complexes. The aromatization/dearomatization processes of ligand backbones are also monitored using magnetic (NICS) and electronic (PDI) indicators of aromaticity, and the consequences to noninnocent behavior are discussed. Finally, the recently developed effective oxidation state (EOS) analysis is utilized, on the one hand, to test its applicability for complexes containing noninnocent ligands, and, on the other hand, to provide new insights into the magnitude of state mixings in the investigated complexes. The effect of ligand substitution, nature of donor atom, ligand frame modification on these manifestations, and measures is discussed in an intuitive and pedagogical manner. PMID- 26866980 TI - Human Exposure and Elimination Kinetics of Chlorinated Polyfluoroalkyl Ether Sulfonic Acids (Cl-PFESAs). AB - The incomplete mass-balance of organic fluorine in human serum indicates the existence of unknown per- and polyfluoroalkyl substances (PFASs) with persistent and bioaccumulative properties. Here we characterized human exposure and elimination kinetics of chlorinated polyfluoroalkyl ether sulfonic acids (Cl PFESAs) in metal plating workers (n = 19), high fish consumers (n = 45), and background controls (n = 8). Cl-PFESAs were detected in >98% of the sampled individuals with serum concentrations ranging <0.019-5040 ng/mL. Statistically higher median serum levels were observed in high fish consumers (93.7 ng/mL) and metal plating workers (51.5 ng/mL) compared to the background control group (4.78 ng/mL) (Kruskal-Wallis rank sum test, p < 0.01). Cl-PFESAs could account for 0.269 to 93.3% of ?PFASs in human serum indicating that this compound class may explain a substantial fraction of previously unidentified organic fluorine in the Chinese population. Estimated half-lives for renal clearance (median 280 years; range 7.1-4230 years) and total elimination (median 15.3 years; range 10.1-56.4 years) for the eight carbon Cl-PFESA suggest that this is the most biopersistent PFAS in humans reported to date. The apparent ubiquitous distribution and slow elimination kinetics in humans underscore the need for more research and regulatory actions on Cl-PFESAs and PFAS alternatives with similar chemical structures. PMID- 26866983 TI - Pegylated Polyaspartamide-Polylactide-Based Nanoparticles Penetrating Cystic Fibrosis Artificial Mucus. AB - Here, the preparation of mucus-penetrating nanoparticles for pulmonary administration of ibuprofen in patients with cystic fibrosis is described. A fluorescent derivative of alpha,beta-poly(N-2-hydroxyethyl)-D,L-aspartamide is synthesized by derivatization with rhodamine, polylactide, and poly(ethylene glycol), to obtain polyaspartamide-polylactide derivatives with different degrees of pegylation. Starting from these copolymers, fluorescent nanoparticles with different poly(ethylene glycol) content, empty and loaded with ibuprofen, showed spherical shape, colloidal size, slightly negative zeta potential, and biocompatibility toward human bronchial epithelial cells. The high surface poly(ethylene glycol) density of fluorescent nanoparticles and poly(ethylene glycol) brush-like conformation assumed on their surface, conferred to pegylated nanoparticles the mucus-penetrating properties, properly demonstrated by assessing their ability to avoid interactions with mucus components and to penetrate cystic fibrosis artificial mucus. Finally, ibuprofen release profile and uptake capacity within human bronchial epithelial cells in the presence of cystic fibrosis artificial mucus showed how these mucus-penetrating nanoparticles could rapidly diffuse through the mucus barrier reaching the mucosal surface, where they could offer a sustained delivery of ibuprofen at the site of disease. PMID- 26866984 TI - Recognizing the Limited Applicability of Job Plots in Studying Host-Guest Interactions in Supramolecular Chemistry. AB - Continuous variation method, known as Job plot, is the most commonly applied method for the determination of stoichiometry of complex chemical entities for over 100 years. Although, the method was proven successful in the analysis of very stable metal-ligand complexes, we demonstrate that its use in supramolecular chemistry often provides false results. We support this statement with multiple simulations as well as cases studies of several real host-guest systems. We propose an alternative, general method relying on the analysis of residual distribution in titration data fitting. The latter method is more convenient compared to the Job plot and unlike it gives correct results in all real cases studied. PMID- 26866982 TI - Filtering genetic variants and placing informative priors based on putative biological function. AB - High-density genetic marker data, especially sequence data, imply an immense multiple testing burden. This can be ameliorated by filtering genetic variants, exploiting or accounting for correlations between variants, jointly testing variants, and by incorporating informative priors. Priors can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. Based on Genetic Analysis Workshop (GAW) 19 data, this article discusses diversity and usefulness of functional variant scores provided, for example, by PolyPhen2, SIFT, or RegulomeDB annotations. Incorporating functional scores into variant filters or weights and adjusting the significance level for correlations between variants yielded significant associations with blood pressure traits in a large family study of Mexican Americans (GAW19 data set). Marker rs218966 in gene PHF14 and rs9836027 in MAP4 significantly associated with hypertension; additionally, rare variants in SNUPN significantly associated with systolic blood pressure. Variant weights strongly influenced the power of kernel methods and burden tests. Apart from variant weights in test statistics, prior weights may also be used when combining test statistics or to informatively weight p values while controlling false discovery rate (FDR). Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure. PMID- 26866985 TI - Undergraduate study in psychology: Curriculum and assessment. AB - The undergraduate curriculum in psychology profoundly reflects and shapes the discipline. Yet, reliable information on the undergraduate psychology curriculum has been difficult to acquire due to insufficient research carried out on unrepresentative program samples with disparate methods. In 2014, APA launched the first systematic effort in a decade to gather national data on the psychology major and program outcomes. We surveyed a stratified random sample of department chairs/coordinators of accredited colleges and universities in the United States that offer undergraduate courses and programs in psychology. A total of 439 undergraduate psychology programs (45.2%) completed the survey. This article summarizes, for both associate and baccalaureate programs, the results of the Undergraduate Study in Psychology. Current practices concerning the introductory course, the courses offered, core requirements, the psychology minor, and tracks/concentrations are presented. The frequency of formal program reviews and program-level assessment methods are also addressed. By extending prior research on the undergraduate curriculum, we chronicle longitudinal changes in the psychology major over the past 20 years. PMID- 26866986 TI - Guidelines for the undergraduate psychology major: Version 2.0. AB - The APA Guidelines for the Undergraduate Psychology Major: Version 2.0 (henceforth Guidelines 2.0; APA, 2013) represents a national effort to describe and develop high-quality undergraduate programs in psychology. The task force charged with the revision of the original guidelines for the undergraduate major examined the success of the document's implementation and made changes to reflect emerging best practices and to integrate psychology's work with benchmarking scholarship in higher education. Guidelines 2.0 abandoned the original distinction drawn between psychology-focused skills and psychology skills that enhance liberal arts development. Instead, Guidelines 2.0 describes five inclusive goals for the undergraduate psychology major and two developmental levels of student learning outcomes. Suggestions for assessment planning are provided for each of the five learning goals. PMID- 26866987 TI - Strengthening introductory psychology: A new model for teaching the introductory course. AB - Introductory psychology (Intro Psych) is one of the most popular and frequently taught courses on college campuses, yet educators in psychology have limited knowledge about what is covered in classes around the nation or the extent to which class content reflects the current scope of the discipline. There is no explicit model to guide course content selection for the intro course, which poses substantial challenges for instructors. This article proposes a new model for teaching the intro course that integrates (a) scientific foundations, (b) 5 major domains or pillars of knowledge (biological, cognitive, developmental, social and personality, and mental and physical health), and (c) cross-cutting themes relevant to all domains (cultural and social diversity, ethics, variations in human functioning, and applications; American Psychological Association, 2014). We advocate for national assessment of the course, a similar introductory course for majors and nonmajors, the inclusion of experiential or laboratory components, and additional training resources for instructors of the intro course. Given the exponential growth of psychological knowledge and applications during the past decades, we caution against attempting to provide exhaustive coverage of all topic areas of psychology in a one-semester course. We conclude by discussing the challenges that lie ahead for the discipline of psychology as it launches this new model for Intro Psych. PMID- 26866988 TI - The new Medical College Admission Test: Implications for teaching psychology. AB - This year's applicants to medical school took a newly revised version of the Medical College Admission Test. Unlike applicants in the past, they were asked to demonstrate their knowledge and use of concepts commonly taught in introductory psychology courses. The new Psychological, Social, and Biological Foundations of Behavior Test asked applicants to demonstrate the ways in which psychological, social, and biological factors influence perceptions and reactions to the world; behavior and behavior change; what people think about themselves and others; the cultural and social differences that influence well-being; and the relationships among social stratification, access to resources, and well-being. Building from the classic biopsychosocial model, this article provides the rationale for testing psychology concepts in application to medical school. It describes the concepts and skills that the new exam tests and shows how they lay the foundation for learning in medical school about the behavioral and sociocultural determinants of health. This article discusses the implications of these changes for undergraduate psychology faculty and psychology curricula as well as their importance to the profession of psychology at large. PMID- 26866989 TI - Internationalizing undergraduate psychology education: Trends, techniques, and technologies. AB - How can we best internationalize undergraduate psychology education in the United States and elsewhere? This question is more timely than ever, for at least 2 reasons: Within the United States, educators and students seek greater contact with psychology programs abroad, and outside the United States, psychology is growing apace, with educators and students in other nations often looking to U.S. curricula and practices as models. In this article, we outline international developments in undergraduate psychology education both in the United States and abroad, and analyze the dramatic rise of online courses and Internet-based technologies from an instructional and international point of view. Building on the recommendations of the 2005 APA Working Group on Internationalizing the Undergraduate Psychology Curriculum, we then advance 14 recommendations on internationalizing undergraduate psychology education--for students, faculty, and institutions. PMID- 26866990 TI - Sarnoff A. Mednick (1928-2015). AB - Presents the obituary of Sarnoff A. Mednick (1928 -2015). Sarnoff A. Mednick was considered among the most important figures in psychopathology research in his generation. He pioneered the high-risk research design and made numerous contributions to our understanding of creativity and of the origins of schizophrenia and criminality. The son of Jewish immigrants, Mednick was born on January 27, 1928, and was raised in the Bronx in New York City, New York. He earned a bachelor's degree from the City College of New York in 1948 and a master's degree from Columbia University. In 1954, he earned his doctorate in psychology from Northwestern University. Following a postdoctoral fellowship at the University of Chicago, he was appointed an instructor at Harvard University and then became a visiting assistant research professor at the University of California, Berkeley (1958 -1959). In 1968, he became a professor at the New School for Social Research in New York, where he taught until 1977, when he joined the faculty at the University of Southern California until his retirement in August 2008. Mednick, professor emeritus of psychology at the University of Southern California, died of natural causes on April 10, 2015, in Toledo, Ohio. He was 87. PMID- 26866991 TI - Robert W. Rieber (1932-2015). AB - Presents the obituary of Robert W. Rieber (1932-2015). Robert W. Rieber, the son of immigrants from the former Austro- Hungarian Empire was born March 24, 1932. He earned a bachelor's degree at Pennsylvania State University and a master's degree in speech pathology at Temple University. He moved to New York City, New York, in 1957, working as a speech pathologist at New York University. In 1960, he accepted an academic position at Pace University, subsequently moving to the John Jay College of Criminal Justice at City University of New York. He held appointments at Columbia University and, following his retirement from John Jay, at Fordham University. Bob founded and edited several journals, including The Journal of Communication Disorders, The Journal of Social Distress and the Homeless, and The Journal of Psycholinguistics Research. While on leave from Pace, he completed his doctorate at the University of London with a dissertation on the relationship between language and psychopathology. Rieber died at his summer home in Maine on April 9, 2015. He was 83. PMID- 26866992 TI - Richard Henry Dana (1927-2015). AB - Richard Henry Dana was born on June 14, 1927, in Bronxville, New York. Dick was accepted to Princeton University in 1944 on a scholarship and graduated in 1949. He then became a student leader in the Congress of Racial Equality and participated in a series of nonviolent sit-in protests. He completed studies for his doctoral degree at the University of Illinois in clinical psychology (1953). He briefly held a series of clinical and university positions until finally settling down at the University of Arkansas (1969- 1988). It was during his long tenure in Arkansas that Dick authored one of the foundational textbooks in clinical psychology. His groundbreaking work, Multicultural Assessment Perspectives for Professional Psychology (1993), provided the first comprehensive book on the topic. Over a remarkable 10-year period, he produced a flurry of scholarly and professional activity. He passed away peacefully at his home in Portland, Oregon, on August 17, 2015. PMID- 26866993 TI - Giuseppe Costantino (1937-2015). AB - Giuseppe Costantino was born in Nocera Terinese, Italy, on December 25, 1937. Giuseppe's personal understanding of the immigrant experience infused his career. He developed Cuento therapies, hero/heroine therapy for adolescents, and the Tell Me-a-Story (TEMAS) tests, which addressed the growing needs of multiculturalism. He served as a junior lieutenant/training officer in the Italian Armed forces, obtained his teaching degree (1955). Costantino immigrated to the United States in 1961. He earned a bachelor's degree in industrial psychology from Baruch College, a master's degree in school psychology from City College, and a doctorate in clinical/community psychology from New York University in 1975. Giuseppe began his career as a caseworker. The bulk of his career was spent in Brooklyn, New York, where he was chief psychologist for 7 years, clinical director for 21 years, and director of research, training, and new programs from 2005 until his death. Giuseppe, a psychologist who dedicated his life to working for minority populations, particularly children, died on February 18, 2015. PMID- 26866995 TI - A general view on the reactivity of the oxygen-functionalized graphene basal plane. AB - In this contribution we inspect the adsorption of H, OH, Cl and Pt on oxidized graphene using DFT calculations. The introduction of epoxy and hydroxyl groups on the graphene basal plane significantly alters its chemisorption properties, which can be attributed to the deformation of the basal plane and the type and distribution of these groups. We show that a general scaling relation exists between the hydrogen binding energies and the binding energies of other investigated adsorbates, which allows for a simple probing of the reactivity of oxidized graphene with only one adsorbate. The electronic states of carbon atoms located within the 2 eV interval below the Fermi level are found to be responsible for the interaction of the basal plane with the chosen adsorbates. The number of electronic states situated in this energy interval is shown to correlate with hydrogen binding energies. PMID- 26866994 TI - Enhancing Paradynamics for QM/MM Sampling of Enzymatic Reactions. AB - Despite the enormous increase in computer power, it is still extremely challenging to obtain computationally converging sampling of ab initio QM/MM (QM(ai)/MM) free energy surfaces in condensed phases. The sampling problem can be significantly reduced by the use of the reference potential paradynamics (PD) approach, but even this approach still requires major computer time in studies of enzymatic reactions. To further reduce the sampling problem we developed here a new PD version where we use an empirical valence bond reference potential that has a minimum rather than a maximum at the transition state region of the target potential (this is accomplished conveniently by shifting the EVB of the product state). Hence, we can map the TS region in a more efficient way. Here, we introduce and validate the inverted EVB PD approach. The validation involves the study of the S(N)2 step of the reaction catalyzed by haloakene dehalogenase (DhlA) and the GTP hydrolysis in the RasGAP system. In addition, we have also studied the corresponding reaction in water for each of the systems described here and the reaction involving trimethylsulfonium and dimethylamine in solution. The results are encouraging and the new strategy appears to provide a powerful way of evaluating QM(ai)/MM activation free energies. PMID- 26866996 TI - Demonstrating an Order-of-Magnitude Sampling Enhancement in Molecular Dynamics Simulations of Complex Protein Systems. AB - Molecular dynamics (MD) simulations can describe protein motions in atomic detail, but transitions between protein conformational states sometimes take place on time scales that are infeasible or very expensive to reach by direct simulation. Enhanced sampling methods, the aim of which is to increase the sampling efficiency of MD simulations, have thus been extensively employed. The effectiveness of such methods when applied to complex biological systems like proteins, however, has been difficult to establish because even enhanced sampling simulations of such systems do not typically reach time scales at which convergence is extensive enough to reliably quantify sampling efficiency. Here, we obtain sufficiently converged simulations of three proteins to evaluate the performance of simulated tempering, a member of a widely used class of enhanced sampling methods that use elevated temperature to accelerate sampling. Simulated tempering simulations with individual lengths of up to 100 MUs were compared to (previously published) conventional MD simulations with individual lengths of up to 1 ms. With two proteins, BPTI and ubiquitin, we evaluated the efficiency of sampling of conformational states near the native state, and for the third, the villin headpiece, we examined the rate of folding and unfolding. Our comparisons demonstrate that simulated tempering can consistently achieve a substantial sampling speedup of an order of magnitude or more relative to conventional MD. PMID- 26866997 TI - Three-Dimensionally Costabilized Metal Catalysts toward an Oxygen Reduction Reaction. AB - Improving the long-term stability of metal catalysts is crucial to developing polymer electrolyte fuel cells (PEFCs). In this work, we first report an inorganic (TiO2)-organic (perfluorosulfonic acid, PFSA) costabilized Pt catalyst supported on graphene nanosheets (GNS) (Pt-PFSA-TiO2/GNS). Herein, TiO2, as a robust wall, impedes the collision between the metal nanoparticles (NPs) in plane along the horizontal x and y axes, while PFSA mainly anchors the metal NPs to constrain detachment along the vertical z axis. The resulting catalyst displays higher oxygen reduction reaction (ORR) activity in comparison to that of commercial Pt/C. Significantly, the stability is particularly better than that of only PFSA- or TiO2-decorated catalysts (Pt-PFSA/GNS or Pt-TiO2/GNS) and far better than that of Pt/C. After 6000 potential cycles, the half-wave potential (E1/2) of Pt-PFSA-TiO2/GNS decreases by only 16 mV, far less than that of Pt/C (56 mV). The excellent electrochemical property of Pt-PFSA-TiO2/GNS is predominantly attributed to the synergistic effect of PFSA and TiO2 in costabilizing the Pt NP by anchoring and blocking Pt NPs in all three spatial directions. The structural dynamics and mechanism of enhanced properties are also discussed. PMID- 26866998 TI - Functional Nucleic Acid Probe for Parallel Monitoring K(+) and Protoporphyrin IX in Living Organisms. AB - Parallel monitoring of K(+) and protoporphyrin IX (PPIX) is of vital importance because they are not only involved in a variety of biological processes but also closely linked to each other in numerous cellular pathways. However, there are currently no existing methods that can meet the requirements for parallel and in vivo detection of K(+) and PPIX in living organisms. Herein, we demonstrated a functional nucleic acid (FNA)-based technique for parallel monitoring of K(+) and PPIX in living animals. Specifically, the selected G-rich FNA probe was selectively induced to form a parallel G-quadruplex by K(+). The parallel G quadruplex then remarkably enhanced the fluorescence of PPIX. Thus, by modulating the fluorescence "turn on" with the G-quadruplex and K(+)/PPIX, both K(+) and PPIX could be detected. After validating the developed method for selective and sensitive detection of K(+) and PPIX in vitro, their dynamic changes in living organisms (i.e., living brains and tumors) following various physiological and pathological processes were simultaneously monitored. The current study not only provides a general method for the detection of metal ions and bioactive molecules but also presents a way to investigate their synergistic functions in the regulation of various biological processes. It may also be helpful for improving the imaging and therapeutic efficacy of PPIX and 5-ALA. PMID- 26866999 TI - Interaction grand potential between calcium-silicate-hydrate nanoparticles at the molecular level. AB - Calcium-silicate-hydrate (or C-S-H), an inosilicate, is the major binding phase in cement pastes and concretes and a porous hydrated material made up of a percolated and dense network of crystalline nanoparticles of a mean apparent spherical diameter of ~5 nm that are each stacks of multiple C-S-H layers. Interaction forces between these nanoparticles are at the origin of C-S-H chemical, physical, and mechanical properties at the meso- and macroscales. These particle interactions and the resulting properties may be affected significantly by nanoparticle density and environmental conditions such as the temperature, relative humidity, or concentration of chemical species in the bulk solution. In this study, we combined grand canonical Monte Carlo simulations and an extension of the mean force integration method to derive the pair potentials. This approach enables realistic simulation of the physical environment surrounding the C-S-H particles. We thus constructed the pair potentials for C-S-H nanoparticles of defined chemical stoichiometry at 10% relative humidity (RH), varying the relative crystallographic orientations at a constant particle density of rhopart ~ 2.21 mmol L(-1). We found that cohesion between nanoparticles is affected strongly by both the aspect ratio and the crystallographic misorientation of interacting particles. This method and the findings underscore the importance of accounting for relative dimensions and orientation among C-S-H nanoparticles in descriptions of physical and simulated multiparticle aggregates or mesoscale systems. PMID- 26867000 TI - Individual differences in subjective alcohol responses and alcohol-related disinhibition. AB - There are important individual differences in acute subjective responses to alcohol, which have often been assessed using self-report measures. There is also evidence of meaningful between-persons variation in alcohol's disinhibiting effects on behavior, such that some individuals become more impaired on tasks of inhibition than do others after an intoxicating dose. The degree to which subjective alcohol responses correspond with these disinhibition effects is not yet clear. In this study, we tested associations among indices of subjective alcohol responses and their correspondence with sensitivity to alcohol-related disinhibition. We recruited recent-binge-drinking emerging adults (N = 82) for a group-administered, placebo-controlled, within-subject, counterbalanced alcohol challenge in a simulated bar laboratory. Confirmatory factor analyses revealed that a 2-factor model with several cross-loadings explained associations among the subjective measures well, replicating a differentiation between stimulant like and sedative-like subjective responses. Controlling sex and placebo performance, participants who reported greater subjective stimulant-like effects but not sedative-like effects-experienced more alcohol-related disinhibition, as measured by cued go/no-go task inhibitory failures. This association was small-to moderate in magnitude. The results of this study highlight the distinction between stimulant-like and sedative-like subjective alcohol effects. They suggest, additionally, that there may be modest commonalities between alcohol's acute impacts on subjective stimulation and objective disinhibition. PMID- 26867001 TI - Tunable optical response of bowtie nanoantenna arrays on thermoplastic substrates. AB - Thermally responsive polymers present an interesting avenue for tuning the optical properties of nanomaterials on their surfaces by varying their periodicity and shape using facile processing methods. Gold bowtie nanoantenna arrays are fabricated using nanosphere lithography on prestressed polyolefin (PO), a thermoplastic polymer, and optical properties are investigated via a combination of spectroscopy and electromagnetic simulations to correlate shape evolution with optical response. Geometric features of bowtie nanoantennas evolve by annealing at temperatures between 105 degrees C and 135 degrees C by releasing the degree of prestress in PO. Due to the higher modulus of Au versus PO, compressive stress occurs on Au bowtie regions on PO, which leads to surface buckling at the two highest annealing temperatures; regions with a 5 nm gap between bowtie nanoantennas are observed and the average reduction is 75%. Reflectance spectroscopy and full-wave electromagnetic simulations both demonstrate the ability to tune the plasmon resonance wavelength with a window of approximately 90 nm in the range of annealing temperatures investigated. Surface enhanced Raman scattering measurements demonstrate that maximum enhancement is observed as the excitation wavelength approaches the plasmon resonance of Au bowtie nanoantennas. Both the size and morphology tunability offered by PO allows for customizing optical response. PMID- 26867002 TI - Dried plum diet protects from bone loss caused by ionizing radiation. AB - Bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone resorbing osteoclasts. Therefore, we evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF alpha) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth. PMID- 26867004 TI - Conjunctival autograft for pterygium. AB - BACKGROUND: A pterygium is a fleshy, wing-shaped growth from the conjunctiva, crossing over the limbus onto the cornea. Prevalence ranges widely around the world. Evidence suggests that ultraviolet light is a major contributor in the formation of pterygia. Pterygia impair vision, limit eye movements, and can cause eye irritation, foreign body sensation, and dryness. In some susceptible patients, the pterygium can grow over the entire corneal surface, blocking the visual axis.Surgery is the only effective treatment for pterygium, though recurrences are common. With simple excision techniques (that is, excising the pterygium and leaving bare sclera), the risk of recurrence has been reported to be upwards of 80%. Pterygium excision combined with a tissue graft has a lower risk of recurrence. In conjunctival autograft surgery, conjunctival tissue from another part of the person's eye along with limbal tissue is resected in one piece and used to cover the area from which the pterygium was excised. Another type of tissue graft surgery for pterygium is amniotic membrane graft, whereby a piece of donor amniotic membrane is fixed to the remaining limbus and bare sclera area after the pterygium has been excised. OBJECTIVES: The objective of this review was to assess the safety and effectiveness of conjunctival autograft (with or without adjunctive therapy) compared with amniotic membrane graft (with or without adjunctive therapy) for pterygium. We also planned to determine whether use of MMC yielded better surgical results and to assess the direct and indirect comparative costs of these procedures. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 10, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched 21 November 2014), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 23 November 2015. SELECTION CRITERIA: We included in this review randomized controlled trials that had compared conjunctival autograft surgery (with or without adjunctive therapy) with amniotic membrane graft surgery (with or without adjunctive therapy) in people with primary or recurrent pterygium. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results and assessed full-text reports from among the potentially eligible trials. Two review authors independently extracted data from the included trials and assessed the trial characteristics and risk of bias. The primary outcome was the risk of recurrence of pterygium at 3 months and 6 months after surgery. We combined results from individual studies in meta-analyses using random-effects models. Risk of recurrence of pterygium was reported using risk ratios to compare conjunctival autograft with amniotic membrane transplant. MAIN RESULTS: We identified 20 studies that had analyzed a total of 1947 eyes of 1866 participants (individual studies ranged from 8 to 346 participants who were randomized). The studies were conducted in eight different countries: one in Brazil, three in China, three in Cuba, one in Egypt, two in Iran, two in Thailand, seven in Turkey, and one in Venezuela. Overall risk of bias was unclear, as many studies did not provide information on randomization methods or masking to prevent performance and detection bias.The risk ratio for recurrence of pterygium using conjunctival autograft versus amniotic membrane transplant was 0.87 (95% confidence interval (CI) 0.43 to 1.77) and 0.53 (95% CI 0.33 to 0.85) at 3 months and 6 months, respectively. These estimates include participants with primary and recurrent pterygia. We performed a subgroup analysis to compare participants with primary pterygia with participants with recurrent pterygia. For participants with primary pterygia, the risk ratio was 0.92 (95% CI 0.37 to 2.30) and 0.58 (95% CI 0.27 to 1.27) at 3 months and 6 months, respectively. We were only able to estimate the recurrence of pterygia at 6 months for participants with recurrent pterygia, and the risk ratio comparing conjunctival autograft with amniotic membrane transplant was 0.45 (95% CI 0.21 to 0.99). One included study was a doctoral thesis and did not use allocation concealment. When this study was excluded in a sensitivity analysis, the risk ratio for pterygium recurrence at 6 months' follow-up was 0.43 (95% CI 0.30 to 0.62) for participants with primary and recurrent pterygium. One of the secondary outcomes, the proportion of participants with clinical improvement, was analyzed in only one study. This study reported clinical outcome as the risk of non-recurrence, which was seen in 93.8% of participants in the conjunctival limbal autograft group and 93.3% in the amniotic membrane transplant group at 3 months after surgery.We did not analyze data on the need for repeat surgery, vision-related quality of life, and direct and indirect costs of surgery due to an insufficient number of studies reporting these outcomes.Thirteen studies reported adverse events associated with conjunctival autograft surgery and amniotic membrane transplant surgery. Adverse events that occurred in more than one study were granuloma and pyogenic granuloma and increased intraocular pressure. None of the included studies reported that participants had developed induced astigmatism. AUTHORS' CONCLUSIONS: In association with pterygium excision, conjunctival autograft is associated with a lower risk of recurrence at six months' after surgery than amniotic membrane transplant. Participants with recurrent pterygia in particular have a lower risk of recurrence when they receive conjunctival autograft surgery compared with amniotic membrane transplant. There are few studies comparing the two techniques with respect to visual acuity outcomes, and we identified no studies that reported on vision-related quality of life or direct or indirect costs. Comparison of these two procedures in such outcome measures bears further investigation. There were an insufficient number of studies that used adjunctive mitomycin C to estimate the effects on pterygium recurrence following conjunctival autograft or amniotic membrane transplant. PMID- 26867003 TI - The role of radiology in diagnosis and management of drug mules: an update with new challenges and new diagnostic tools. AB - Emergency physicians and radiologists have been increasingly encountering internal concealment of illegal drugs. The packages commonly contain powdered solid drugs such as cocaine, heroin, methamphetamine and hashish, but they may also contain cocaine in the liquid form. The second type of package has recently been more commonly encountered, and poses a greater diagnostic challenge. As clinical evaluation and laboratory tests frequently fail to make the correct diagnosis, imaging examination is typically required. Imaging methods assume a vital role in the diagnosis, follow-up and management. Abdominal X-ray, ultrasonography, CT and MRI are used for the imaging purposes. Among the aforementioned methods, low-dose CT is state-of-the-art in these cases. It is of paramount importance that radiologists have a full knowledge of the imaging characteristics of these packages and accurately guide physicians and security officials. PMID- 26867005 TI - Distance-Dependent Plasmon-Enhanced Singlet Oxygen Production and Emission for Bacterial Inactivation. AB - Herein, we synthesized a series of 10 core-shell silver-silica nanoparticles with a photosensitizer, Rose Bengal, tethered to their surface. Each nanoparticle possesses an identical silver core of about 67 nm, but presents a different silica shell thickness ranging from 5 to 100 nm. These hybrid plasmonic nanoparticles thus afford a plasmonic nanostructure platform with a source of singlet oxygen ((1)O2) at a well-defined distance from the metallic core. Via time-resolved and steady state spectroscopic techniques, we demonstrate the silver core exerts a dual role of enhancing both the production of (1)O2, through enhanced absorption of light, and its radiative decay, which in turn boosts (1)O2 phosphorescence emission to a greater extent. Furthermore, we show both the production and emission of (1)O2 in vitro to be dependent on proximity to the plasmonic nanostructure. Our results clearly exhibit three distinct regimes as the plasmonic nanostructure moves apart from the (1)O2 source, with a greater enhancement for silica shell thicknesses ranging between 10 and 20 nm. Moreover, these hybrid plasmonic nanoparticles can be delivered to both Gram-positive and Gram-negative bacteria boosting both photoantibacterial activity and detection limit of (1)O2 in cells. PMID- 26867006 TI - Understanding Charge Transport in Mixed Networks of Semiconducting Carbon Nanotubes. AB - The ability to select and enrich semiconducting single-walled carbon nanotubes (SWNT) with high purity has led to a fast rise of solution-processed nanotube network field-effect transistors (FETs) with high carrier mobilities and on/off current ratios. However, it remains an open question whether it is best to use a network of only one nanotube species (monochiral) or whether a mix of purely semiconducting nanotubes but with different bandgaps is sufficient for high performance FETs. For a range of different polymer-sorted semiconducting SWNT networks, we demonstrate that a very small amount of narrow bandgap nanotubes within a dense network of large bandgap nanotubes can dominate the transport and thus severely limit on-currents and effective carrier mobility. Using gate voltage-dependent electroluminescence, we spatially and spectrally reveal preferential charge transport that does not depend on nominal network density but on the energy level distribution within the network and carrier density. On the basis of these results, we outline rational guidelines for the use of mixed SWNT networks to obtain high performance FETs while reducing the cost for purification. PMID- 26867007 TI - Angiotensin II Type 2 Receptor Decreases Transforming Growth Factor-beta Type II Receptor Expression and Function in Human Renal Proximal Tubule Cells. AB - Transforming growth factor-beta (TGF-beta), via its receptors, induces epithelial mesenchymal transition (EMT) and plays an important role in the development of renal tubulointersitial fibrosis. Angiotensin II type 2 receptor (AT2R), which mediates beneficial renal physiological functions, has received attention as a prospective therapeutic target for renoprotection. In this study, we investigated the effect and underlying mechanism of AT2R on the TGF-beta receptor II (TGF betaRII) expression and function in human proximal tubular cells (HK-2). Here, we show that the AT2R agonist CGP42112A decreased TGF-betaRII protein expression in a concentration- and time-dependent manner in HK-2 cells. The inhibitory effect of the AT2R on TGF-betaRII expression was blocked by the AT2R antagonists PD123319 or PD123177. Stimulation with TGF-beta1 enhanced EMT in HK-2 cells, which was prevented by pre-treatment with CGP42112A. One of mechanisms in this regulation is associated with the increased TGF-betaRII degradation after activation of AT2R. Furthermore, laser confocal immunofluorescence microscopy showed that AT2R and TGF-betaRII colocalized in HK-2 cells. AT2R and TGF-betaRII coimmunoprecipitated and this interaction was increased after AT2R agonist stimulation for 30 min. The inhibitory effect of the AT2R on TGF-betaRII expression was also blocked by the nitric oxide synthase inhibitor L-NAME, indicating that nitric oxide is involved in the signaling pathway. Taken together, our study indicates that the renal AT2R regulates TGF-betaRII expression and function via the nitric oxide pathway, which may be important in the control of renal tubulointerstitial fibrosis. PMID- 26867008 TI - A Splice Variant of Bardet-Biedl Syndrome 5 (BBS5) Protein that Is Selectively Expressed in Retina. AB - PURPOSE: Bardet-Biedl syndrome is a complex ciliopathy that usually manifests with some form of retinal degeneration, amongst other ciliary-related deficiencies. One of the genetic causes of this syndrome results from a defect in Bardet-Biedl Syndrome 5 (BBS5) protein. BBS5 is one component of the BBSome, a complex of proteins that regulates the protein composition in cilia. In this study, we identify a smaller molecular mass form of BBS5 as a variant formed by alternative splicing and show that expression of this splice variant is restricted to the retina. METHODS: Reverse transcription PCR from RNA was used to isolate and identify potential alternative transcripts of Bbs5. A peptide unique to the C-terminus of the BBS5 splice variant was synthesized and used to prepare antibodies that selectively recognized the BBS5 splice variant. These antibodies were used on immunoblots of tissue extracts to determine the extent of expression of the alternative transcript and on tissue slices to determine the localization of expressed protein. Pull-down of fluorescently labeled arrestin1 by immunoprecipitation of the BBS5 splice variant was performed to assess functional interaction between the two proteins. RESULTS: PCR from mouse retinal cDNA using Bbs5-specific primers amplified a unique cDNA that was shown to be a splice variant of BBS5 resulting from the use of cryptic splicing sites in Intron 7. The resulting transcript codes for a truncated form of the BBS5 protein with a unique 24 amino acid C-terminus, and predicted 26.5 kD molecular mass. PCR screening of RNA isolated from various ciliated tissues and immunoblots of protein extracts from these same tissues showed that this splice variant was expressed in retina, but not brain, heart, kidney, or testes. Quantitative PCR showed that the splice variant transcript is 8.9-fold (+/- 1.1-fold) less abundant than the full-length transcript. In the retina, the splice variant of BBS5 appears to be most abundant in the connecting cilium of photoreceptors, where BBS5 is also localized. Like BBS5, the binding of BBS5L to arrestin1 can be modulated by phosphorylation through protein kinase C. CONCLUSIONS: In this study we have identified a novel splice variant of BBS5 that appears to be expressed only in the retina. The BBS5 splice variant is expressed at approximately 10% of full-length BBS5 level. No unique functional or localization properties could be identified for the splice variant compared to BBS5. PMID- 26867011 TI - Prediction of the intramembranous tissue formation during perisprosthetic healing with uncertainties. Part 2. Global clinical healing due to combination of random sources. AB - This work proposes to examine the variability of the bone tissue healing process in the early period after the implantation surgery. The first part took into account the effect of variability of individual biochemical factors on the solid phase fraction, which is an indicator of the quality of the primary fixation and condition of its long-term behaviour. The next issue, addressed in this second part, is the effect of cumulative sources of uncertainties on the same problem of a canine implant. This paper is concerned with the ability to increase the number of random parameters to assess the coupled influence of those variabilities on the tissue healing. To avoid an excessive increase in the complexity of the numerical modelling and further, to maintain efficiency in computational cost, a collocation-based polynomial chaos expansion approach is implemented. A progressive set of simulations with an increasing number of sources of uncertainty is performed. This information is helpful for future implant design and decision process for the implantation surgical act. PMID- 26867010 TI - Factor Xa Inhibitor Suppresses the Release of Phosphorylated HSP27 from Collagen Stimulated Human Platelets: Inhibition of HSP27 Phosphorylation via p44/p42 MAP Kinase. AB - Selective inhibitors of factor Xa (FXa) are widely recognized as useful therapeutic tools for stroke prevention in non-valvular atrial fibrillation or venous thrombosis. Thrombin, which is rapidly generated from pro-thrombin through the activation of factor X to FXa, acts as a potent activator of human platelets. Thus, the reduction of thrombin generation by FXa inhibitor eventually causes a suppressive effect on platelet aggregation. However, little is known whether FXa inhibitors directly affect the function of human platelets. We have previously reported that collagen induces the phosphorylation of heat shock protein 27 (HSP27), a low-molecular weight heat shock protein via Rac-dependent activation of p44/p42 mitogen-activated protein (MAP) kinase in human platelets, eventually resulting in the release of HSP27. In the present study, we investigated the direct effect of FXa inhibitor on the collagen-induced human platelet activation. Rivaroxaban as well as edoxaban significantly reduced the collagen-induced phosphorylation of both HSP27 and p44/p42 MAP kinase without affecting the platelet aggregation. Rivaroxaban significantly inhibited the release of phosphorylated HSP27 from collagen-stimulated platelets but not the secretion of platelet derived growth factor-AB. In patients administrated with rivaroxaban, the collagen-induced levels of phosphorylated HSP27 were markedly diminished after 2 days of administration, which failed to affect the platelet aggregation. These results strongly suggest that FXa inhibitor reduces the collagen-stimulated release of phosphorylated HSP27 from human platelets due to the inhibition of HSP27 phosphorylation via p44/p42 MAP kinase. PMID- 26867009 TI - The Adenovirus E4orf4 Protein Provides a Novel Mechanism for Inhibition of the DNA Damage Response. AB - The DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger apoptosis or senescence. Various DDR branches are regulated by kinases of the phosphatidylinositol 3-kinase-like protein kinase family, including ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR). Replication intermediates and linear double-stranded genomes of DNA viruses are perceived by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. As part of its attack on the DDR, adenovirus utilizes various viral proteins to cause degradation of DDR proteins and to sequester the MRN damage sensor outside virus replication centers. Here we show that adenovirus evolved yet another novel mechanism to inhibit the DDR. The E4orf4 protein, together with its cellular partner PP2A, reduces phosphorylation of ATM and ATR substrates in virus-infected cells and in cells treated with DNA damaging drugs, and causes accumulation of damaged DNA in the drug-treated cells. ATM and ATR are not mutually required for inhibition of their signaling pathways by E4orf4. ATM and ATR deficiency as well as E4orf4 expression enhance infection efficiency. Furthermore, E4orf4, previously reported to induce cancer-specific cell death when expressed alone, sensitizes cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibits DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death as many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. PMID- 26867012 TI - Comparative Evaluation of Partial alpha2 -Adrenoceptor Agonist and Pure alpha2 Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice. AB - As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial alpha2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of alpha2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated with alcohol withdrawal. PMID- 26867013 TI - C6: A Monoclonal Antibody Specific for a Fibronectin Epitope Situated at the Interface between the Oncofoetal Extra-Domain B and the Repeat III8. AB - BACKGROUND: Fibronectin (FN) is a large multidomain molecule that is involved in many cellular processes. Different FN isoforms arise from alternative splicing of the pre-mRNA including, most notably, the FN isoform that contains the "extra domain-B" (ED-B). The FN isoform containing ED-B (known as B-FN) is undetectable in healthy adult tissues but is present in large amounts in neoplastic and foetal tissues as well as on the blood vessels during angiogenesis. Thus, antibodies specific for B-FN can be useful for detecting and targeting neoplastic tissues in vivo. We previously characterised C6, a new monoclonal antibody specific for human B-FN and we suggested that it reacts with the B-C loop of the type III repeat 8 which is masked in FN isoforms lacking ED-B and that the insertion of ED B in FN molecules unmasked it. Here we have now consolidated and refined the characterization of this B-FN specific antibody demonstrating that the epitope recognized by C6 also includes loop E-F of ED-B. METHODOLOGY: We built the three dimensional model of the variable regions of the mAb C6 and of the FN fragment EDB-III8 and performed protein:protein docking simulation using the web server ClusPro2.0. To confirm the data obtained by protein:protein docking we generated mutant fragments of the recombinant FN fragment EDB-III8 and tested their reactivity with C6. CONCLUSION: The monoclonal antibody C6 reacts with an epitope formed by the B-C loop of domain III8 and the E-F loop of ED-B. Both loops are required for an immunological reaction, thus this monoclonal is strictly specific for B-FN but the part of the epitope on III8 confers the human specificity. PMID- 26867014 TI - Muscle Synergies Heavily Influence the Neural Control of Arm Endpoint Stiffness and Energy Consumption. AB - Much debate has arisen from research on muscle synergies with respect to both limb impedance control and energy consumption. Studies of limb impedance control in the context of reaching movements and postural tasks have produced divergent findings, and this study explores whether the use of synergies by the central nervous system (CNS) can resolve these findings and also provide insights on mechanisms of energy consumption. In this study, we phrase these debates at the conceptual level of interactions between neural degrees of freedom and tasks constraints. This allows us to examine the ability of experimentally-observed synergies--correlated muscle activations--to control both energy consumption and the stiffness component of limb endpoint impedance. In our nominal 6-muscle planar arm model, muscle synergies and the desired size, shape, and orientation of endpoint stiffness ellipses, are expressed as linear constraints that define the set of feasible muscle activation patterns. Quadratic programming allows us to predict whether and how energy consumption can be minimized throughout the workspace of the limb given those linear constraints. We show that the presence of synergies drastically decreases the ability of the CNS to vary the properties of the endpoint stiffness and can even preclude the ability to minimize energy. Furthermore, the capacity to minimize energy consumption--when available--can be greatly affected by arm posture. Our computational approach helps reconcile divergent findings and conclusions about task-specific regulation of endpoint stiffness and energy consumption in the context of synergies. But more generally, these results provide further evidence that the benefits and disadvantages of muscle synergies go hand-in-hand with the structure of feasible muscle activation patterns afforded by the mechanics of the limb and task constraints. These insights will help design experiments to elucidate the interplay between synergies and the mechanisms of learning, plasticity, versatility and pathology in neuromuscular systems. PMID- 26867015 TI - Roles of MPBQ-MT in Promoting alpha/gamma-Tocopherol Production and Photosynthesis under High Light in Lettuce. AB - 2-methyl-6-phytyl-1, 4-benzoquinol methyltransferase (MPBQ-MT) is a vital enzyme catalyzing a key methylation step in both alpha/gamma-tocopherol and plastoquinone biosynthetic pathway. In this study, the gene encoding MPBQ-MT was isolated from lettuce (Lactuca sativa) by rapid amplification of cDNA ends (RACE), named LsMT. Overexpression of LsMT in lettuce brought about a significant increase of alpha- and gamma-tocopherol contents with a reduction of phylloquinone (vitamin K1) content, suggesting a competition for a common substrate phytyl diphosphate (PDP) between the two biosynthetic pathways. Besides, overexpression of LsMT significantly increased plastoquinone (PQ) level. The increase of tocopherol and plastoquinone levels by LsMT overexpression conduced to the improvement of plants' tolerance and photosynthesis under high light stress, by directing excessive light energy toward photosynthetic production rather than toward generation of more photooxidative damage. These findings suggest that the role and function of MPBQ-MT can be further explored for enhancing vitamin E value, strengthening photosynthesis and phototolerance under high light in plants. PMID- 26867016 TI - Inhibition of Monoacylglycerol Lipase Activity Decreases Glucose-Stimulated Insulin Secretion in INS-1 (832/13) Cells and Rat Islets. AB - Lipid signals derived from lipolysis and membrane phospholipids play an important role in glucose-stimulated insulin secretion (GSIS), though the exact secondary signals remain unclear. Previous reports have documented a stimulatory role of exogenously added mono-acyl-glycerol (MAG) on insulin secretion from cultured beta-cells and islets. In this report we have determined effects of increasing intracellular MAG in the beta-cell by inhibiting mono-acyl-glycerol lipase (MGL) activity, which catalyzes the final step in triacylglycerol breakdown, namely the hydrolysis of MAG to glycerol and free fatty acid (FA). To determine the role of MGL in GSIS, we used three different pharmacological agents (JZL184, MJN110 and URB602). All three inhibited GSIS and depolarization-induced insulin secretion in INS-1 (832/13). JZL184 significantly inhibited both GSIS and depolarization induced insulin secretion in rat islets. JZL184 significantly decreased lipolysis and increased both mono- and diacyglycerol species in INS-1 cells. Analysis of the kinetics of GSIS showed that inhibition was greater during the sustained phase of secretion. A similar pattern was observed in the response of Ca2+ to glucose and depolarization but to a lesser degree suggesting that altered Ca2+ handling alone could not explain the reduction in insulin secretion. In addition, a significant reduction in long chain-CoA (LC-CoA) was observed in INS-1 cells at both basal and stimulatory glucose following inhibition of MGL. Our data implicate an important role for MGL in insulin secretion. PMID- 26867017 TI - Visual Recognition Software for Binary Classification and Its Application to Spruce Pollen Identification. AB - Discriminating between black and white spruce (Picea mariana and Picea glauca) is a difficult palynological classification problem that, if solved, would provide valuable data for paleoclimate reconstructions. We developed an open-source visual recognition software (ARLO, Automated Recognition with Layered Optimization) capable of differentiating between these two species at an accuracy on par with human experts. The system applies pattern recognition and machine learning to the analysis of pollen images and discovers general-purpose image features, defined by simple features of lines and grids of pixels taken at different dimensions, size, spacing, and resolution. It adapts to a given problem by searching for the most effective combination of both feature representation and learning strategy. This results in a powerful and flexible framework for image classification. We worked with images acquired using an automated slide scanner. We first applied a hash-based "pollen spotting" model to segment pollen grains from the slide background. We next tested ARLO's ability to reconstruct black to white spruce pollen ratios using artificially constructed slides of known ratios. We then developed a more scalable hash-based method of image analysis that was able to distinguish between the pollen of black and white spruce with an estimated accuracy of 83.61%, comparable to human expert performance. Our results demonstrate the capability of machine learning systems to automate challenging taxonomic classifications in pollen analysis, and our success with simple image representations suggests that our approach is generalizable to many other object recognition problems. PMID- 26867018 TI - Oncological and functional outcomes 1 year after radical prostatectomy for very low-risk prostate cancer: results from the prospective LAPPRO trial. AB - OBJECTIVES: To analyse oncological and functional outcomes 12 months after treatment of very-low-risk prostate cancer with radical prostatectomy in men who could have been candidates for active surveillance. PATIENTS AND METHODS: We conducted a prospective study of all men with very-low-risk prostate cancer who underwent radical prostatectomy at one of 14 participating centres. Validated patient questionnaires were collected at baseline and after 12 months by independent healthcare researchers. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) >=0.25 ng/mL or treatment with salvage radiotherapy or with hormones. Urinary continence was defined as <1 pad changed per 24 h. Erectile function was defined as ability to achieve erection hard enough for penetration more than half of the time after sexual stimulation. Changes in tumour grade and stage were obtained from pathology reports. We report descriptive frequencies and proportions of men who had each outcome in various subgroups. Fisher's exact test was used to assess differences between the age groups. RESULTS: Of the 4003 men in the LAPPRO cohort, 338 men fulfilled the preoperative national criteria for very-low-risk prostate cancer. Adverse pathology outcomes included upgrading, defined as pT3 or postoperative Gleason sum >=7, which was present in 35% of the men (115/333) and positive surgical margins, which were present in 16% of the men (54/329). Only 2.1% of the men (7/329) had a PSA concentration >0.1 ng/mL 6-12 weeks postoperatively. Erectile function and urinary continence were observed in 44% (98/222) and 84% of the men (264/315), respectively, 12 months postoperatively. The proportion of men achieving the trifecta, defined as preoperative potent and continent men who remained potent and continent with no BCR, was 38% (84/221 men) at 12 months. CONCLUSIONS: Our prospective study of men with very-low-risk prostate cancer undergoing open or robot-assisted radical prostatectomy showed that there were favourable oncological outcomes in approximately two-thirds. Approximately 40% did not have surgically induced urinary incontinence or erectile dysfunction 12 months postoperatively. These results provide additional support for the use of active surveillance in men with very-low-risk prostate cancer; however, the number of men with risk of upgrading and upstaging is not negligible. Improved stratification is still urgently needed. PMID- 26867019 TI - Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity. AB - Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate-self-healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe(3+) complex exhibits the most promising results, to the instant ~52% blockage in tubules within 4 min and ~87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex-mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity. PMID- 26867020 TI - Correlation of Choline/Creatine and Apparent Diffusion Coefficient values with the prognostic parameters of Head and Neck Squamous Cell Carcinoma. AB - The aim of this study was to measure choline/creatine (Ch/Cr) levels through (1)H MRS and apparent diffusion coefficient (ADC) values through diffusion-weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved this study and informed written consent was obtained from all study participants. A prospective study of 43 patients (31 men and 12 women; mean age, 65 years) with HNSCC was conducted. Single-voxel (1)H-MRS was performed at the tumor or metastatic cervical lymph node with point-resolved spectroscopy (PRESS) at TE = 135 ms. Diffusion-weighted MR images with b values of 0, 500 and 1000 s/mm(2) and contrast MRI of the head and neck were performed. The Ch/Cr levels and ADC values of HNSCC were calculated. The gross tumor volume (GTV) was also calculated. The degree of tumor differentiation was determined through pathological examination. The HNSCC Ch/Cr level was negatively correlated with the ADC value (r = -0.662, p = 0.001). There was a significant difference in the Ch/Cr and ADC values at different degrees of tumor differentiation (p = 0.003 and p = 0.001) and with different GTVs (p = 0.122 and p = 0.001). The following prognostic parameter categories were used: (i) poorly differentiated and undifferentiated versus well differentiated to moderately differentiated; and (ii) HNSCC with GTV < 30 cm(3) versus GTV > 30 cm(3). The cut-off values for Cho/Cr and ADC for each category were 1.83, 0.95 and 1.94, 0.99, respectively, and the areas under the curve were 0.771, 0.967 and 0.726, 0.795, respectively, for each category. We conclude that the Ch/Cr levels determined using (1)H-MRS and the ADC values are well correlated with several prognostic parameters of HNSCC. PMID- 26867021 TI - Repeatability Using Automatic Tracing with Canon OCT- HS100 and Zeiss Cirrus HD OCT 5000. AB - BACKGROUND: Optical coherence tomography (OCT), can be used in clinical practice to provide high resolution cross-sectional images of the retina, optic disc and macula structure. These measurements can be useful for early detection, diagnosis, monitoring and treatment guidance for retinal diseases. Therefore, repeatability of measurements in OCT is of great importance. METHODS: Macula and optic disc parameters from the right eye of 30 healthy subjects were obtained twice with the Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. Repeatability was evaluated by use of the coefficient of repeatability (CR) and the coefficient of repeatability as a percentage of the mean (CR%), and the obtained measurements were compared between the instruments. RESULTS: CR% of optic disc parameters ranged between 0.90 and 22.22% and 0.00 and 16.00% with the Canon and Zeiss OCT respectively. For macular parameters CR% ranged between 0.62 and 2.81% and 0.99 and 1.81% with the Canon and Zeiss OCT respectively. No statistical difference could be found when comparing the CR of all macular and disc measurements between the instruments. Compared to our previously published data repeatability has significantly improved with the inclusion of automatic tracking systems with both the Canon and Zeiss OCT. CONCLUSION: Automatic tracking function improves repeatability in both Canon OCT-HS100 and Zeiss Cirrus HD-OCT 5000. However, measurements generated by the two instruments are still not interchangeable. PMID- 26867022 TI - Monitoring the Location of Staff via Mobile Devices in a Large Multifacility Practice Group. AB - We describe a novel location and timekeeping system for a large, multifacility practice group using an app installed on mobile devices belonging to the staff. The system can be used independently of physical time clocks and without extracting information from anesthesia information management systems. The app creates geofences, reporting automatically when the user enters or departs the vicinity of a facility. The app displays the location of staff at all facilities, providing situational awareness. The leaving order of staff was adjusted daily using app data for the previous workload. This was successful; overtime was more evenly distributed year on year. Acceptance of the system was excellent. PMID- 26867023 TI - Identification and Treatment of New Inflammatory Triggers for Complex Regional Pain Syndrome: Small Intestinal Bacterial Overgrowth and Obstructive Sleep Apnea. AB - Complex regional pain syndrome (CRPS) is evoked by conditions that may be associated with local and/or systemic inflammation. We present a case of long standing CRPS in a patient with Ehlers-Danlos syndrome in which prolonged remission was attained by directing therapy toward concomitant small intestinal bacterial overgrowth, obstructive sleep apnea, and potential increased microglia activity. We theorize that cytokine production produced by small intestinal bacterial overgrowth and obstructive sleep apnea may act as stimuli for ongoing CRPS symptoms. CRPS may also benefit from the properties of low-dose naltrexone that blocks microglia Toll-like receptors and induces production of endorphins that regulate and reduce inflammation. PMID- 26867024 TI - Optimizing Viral Discovery in Bats. AB - Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007-2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches. PMID- 26867026 TI - MRI Assessment of Ischemic Lesion Evolution within White and Gray Matter. AB - BACKGROUND: In acute ischemic stroke (AIS), gray matter (GM) and white matter (WM) have different vulnerabilities to ischemia. Thus, we compared the evolution of ischemic lesions within WM and GM using MRI. METHODS: From a European multicenter prospective database (I-KNOW), available T1-weighted images were identified for 50 patients presenting with an anterior AIS and a perfusion weighted imaging (PWI)/diffusion weighted imaging (DWI) mismatch ratio of 1.2 or more. Six lesion compartments were outlined: initial DWI (b = 1,000 s/mm2) lesion, initial PWI-DWI mismatch (Tmax >4 s and DWI-negative), final infarct mapped on 1-month fluid-attenuated inversion recovery (FLAIR) imaging, lesion growth between acute DWI and 1-month FLAIR, DWI lesion reversal at 1 month and salvaged mismatch. The WM and GM were segmented on T1-weighted images, and all images were co-registered within subjects to the baseline MRI. WM and GM proportions were calculated for each compartment. RESULTS: Fifty patients were eligible for the study. Median delay between symptom onset and baseline MRI was 140 min. The percentage of WM was significantly greater in the following compartments: initial mismatch (52.5 vs. 47.5%, p = 0.003), final infarct (56.7 vs. 43.3%, p < 0.001) and lesion growth (58.9 vs. 41.2%, p < 0.001). No significant difference was found between GM and WM percentages within the initial DWI lesion, DWI reversal and salvaged mismatch compartments. CONCLUSIONS: Ischemic lesions may extend preferentially within the WM. Specific therapeutic strategies targeting WM ischemic processes may deserve further investigation. PMID- 26867027 TI - Liver capsule: Mechanisms of alcoholic hepatitis. PMID- 26867025 TI - Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas. AB - The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies. The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease and the diversity of its triatomine vectors. Over 730 triatomines were light-trapped in four geomorphological landscapes shaping French-Guiana, and we determined their taxonomic status and infection by Trypanosoma cruzi. We used a model selection approach to unravel the spatial and temporal variations in species abundance, diversity and infection. The vector community in French-Guiana is typically made of one key species (Panstrongylus geniculatus) that is more abundant than three secondary species combined (Rhodnius pictipes, Panstrongylus lignarius and Eratyrus mucronatus), and four other species that complete the assemblage. Although the overall abundance of adult triatomines does not vary across French Guiana, their diversity increases along a coastal-inland gradient. These variations unravelled a non-monotonic relationship between vector biodiversity and the risk of transmission of Chagas disease, so that intermediate biodiversity levels are associated with the lowest risks. We also observed biannual variations in triatomine abundance, representing the first report of a biannual pattern in the risk of Chagas disease transmission. Those variations were highly and negatively correlated with the average monthly rainfall. We discuss the implications of these patterns for the transmission of T. cruzi by assemblages of triatomine species, and for the dual challenge of controlling Amazonian vector communities that are made of both highly diverse and mostly intrusive species. PMID- 26867028 TI - Childbirth or termination of pregnancy: does paid employment matter? A population study of women in reproductive age in Norway. AB - INTRODUCTION: We studied whether female paid employment is associated with pregnancy outcome; childbirth or pregnancy termination. MATERIAL AND METHODS: All women in Norway, 16-54 years of age, during the years 2007-10 were included. Data sources were; the Norwegian Central Person Registry, the Medical Birth Registry of Norway, and the Registry of Pregnancy Termination. We compared the proportion without paid employment among all women, women who gave birth, and among women who requested termination of pregnancy. Thereafter, and among pregnant women, we estimated the odds ratio for pregnancy termination request for women without paid employment by applying logistic regression analyses, using women with paid employment as reference. RESULTS: Among all women 16-54 years of age, 23.5% were without paid employment. Among women who gave birth, 15.8% were without paid employment, whereas this proportion was 46.4% among women who requested pregnancy termination (p < 0.05). Among the 307 512 women who were pregnant, 60 734 (19.4%) requested pregnancy termination. The odds ratio for pregnancy termination request was 3.18 (95% CI 3.11-3.25) for women without paid employment. Adjustments were made for age, number of children, and region of residence in Norway. CONCLUSION: Being without paid employment was more common among women in the general population and among women requesting pregnancy termination than among women who gave birth. Hence, women seem to have children when they are in paid employment. The role of women's paid employment for reproductive choices should be further investigated. PMID- 26867029 TI - Fascia Origin of Adipose Cells. AB - Adipocytes might arise from vascular stromal cells, pericytes and endothelia within adipose tissue or from bone marrow cells resident in nonadipose tissue. Here, we identified adipose precursor cells resident in fascia, an uninterrupted sheet of connective tissue that extends throughout the body. The cells and fragments of superficial fascia from the rat hindlimb were highly capable of spontaneous and induced adipogenic differentiation but not myogenic and osteogenic differentiation. Fascial preadipocytes expressed multiple markers of adipogenic progenitors, similar to subcutaneous adipose-derived stromal cells (ASCs) but discriminative from visceral ASCs. Such preadipocytes resided in fascial vasculature and were physiologically active in vivo. In growing rats, adipocytes dynamically arose from the adventitia to form a thin adipose layer in the fascia. Later, some adipocytes appeared to overlay on top of other adipocytes, an early sign for the formation of three-dimensional adipose tissue in fascia. The primitive adipose lobules extended invariably along blood vessels toward the distal fascia areas. At the lobule front, nascent capillaries wrapped and passed ahead of mature adipocytes to form the distal neovasculature niche, which might replenish the pool of preadipocytes and supply nutrients and hormones necessary for continuous adipogenesis. Our findings suggest a novel model for the origin of adipocytes from the fascia, which explains both neogenesis and expansion of adipose tissue. Fascial preadipocytes generate adipose cells to form primitive adipose lobules in superficial fascia, a subcutaneous nonadipose tissue. With continuous adipogenesis, these primitive adipose lobules newly formed in superficial fascia may be the rudiment of subcutaneous adipose tissue. Stem Cells 2016;34:1407-1419. PMID- 26867030 TI - The Impact of Methylprednisolone Pulses during Relapses of Multiple Sclerosis on the Kinetics of Anti-Interferon-Beta Antibodies. AB - BACKGROUND/AIMS: We assessed the, hitherto unknown, impact of intravenous methylprednisolone (ivMP) pulses during relapses of multiple sclerosis (MS) on the kinetics of anti-interferon-beta neutralizing antibodies (Nabs) and binding antibodies (Babs). METHODS: Babs (ELISA) and Nabs (antiviral cytopathic effect assay) titers were evaluated before, immediately after and at 1 month following ivMP in 60 MS patients. RESULTS: ivMP reduces Nabs and Babs titers for at least 1 month. Baseline titers determine Nabs and Babs seronegativity at the end of ivMP. Clinical response to ivMP tends to be better in Nabs(+) patients. CONCLUSION: Sampling for Nabs/Babs should be avoided during or shortly after ivMP to avoid transient positive or negative results that may obscure the decision to switch treatment. PMID- 26867031 TI - Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen Years Promoting Rheumatology Educators and Education. AB - OBJECTIVE: The Rheumatology Research Foundation's Clinician Scholar Educator (CSE) award is a 3-year career development award supporting medical education research while providing opportunities for mentorship and collaboration. Our objective was to document the individual and institutional impact of the award since its inception, as well as its promise to strengthen the subspecialty of rheumatology. METHODS: All 60 CSE Award recipients were surveyed periodically. Fifty-six of those 60 awardees (90%) responded to requests for survey information that included post-award activities, promotions, and further funding. Data were also collected from yearly written progress reports for each grant. RESULTS: Of the total CSE recipients to date, 48 of 60 (80%) are adult rheumatologists, 11 of 60 (18%) are pediatric rheumatologists, and 1 is an adult and pediatric rheumatologist. Two-thirds of survey respondents spend up to 30% of their total time in educational activities, and one-third spend greater than 30%. Thirty-one of the 60 CSE recipients (52%) have published a total of 86 medical education papers. Twenty-six of 52 (50%) had received an academic promotion following the award. Eleven awardees earned advanced degrees. CONCLUSION: We describe the creation and evolution of a grant program from a medical subspecialty society foundation and the impact on producing education research, individual identity formation, and ongoing support for educators. This community of rheumatology scholar educators now serves as an important resource at the national level for the American College of Rheumatology and its membership. We believe that this grant may serve as a model for other medical societies that want to promote education scholarship and leadership within their specialties. PMID- 26867032 TI - Reply. PMID- 26867033 TI - Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. AB - OBJECTIVE: The American College of Rheumatology guidelines for the treatment of lupus nephritis recommend change in induction therapy when response to therapy has not occurred within 6 months. Response is not defined, and renal fibrosis can occur while waiting for this end point. Therefore, a decision support tool to better define response is needed to guide clinicians when starting patients on therapy. This study was undertaken to identify biomarker models with sufficient predictive power to develop such a tool. METHODS: Urine samples from 140 patients with biopsy-proven lupus nephritis who had not yet started induction therapy were analyzed for a panel of urinary biomarkers. Univariate receiver operating characteristic (ROC) curves were generated for each individual biomarker and compared to the ROC area under the curve values from machine learning models developed using random forest algorithms. Biomarker models of outcome developed with novel markers in addition to clinical markers were compared to those developed with traditional clinical markers alone. RESULTS: Models developed with the combined traditional and novel biomarker panels demonstrated clinically meaningful predictive power. Markers most predictive of response were chemokines, cytokines, and markers of cellular damage. CONCLUSION: This is the first study to demonstrate the power of low-abundance biomarker panels and machine learning algorithms for predicting lupus nephritis outcomes. This is a critical first step in research to develop clinically meaningful decision support tools. PMID- 26867035 TI - The orthopedic characterization of Goltz syndrome. AB - Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare condition in which congenital anomalies result in a multitude of defects that affect many systems of the body. These defects can involve the eyes, skin, teeth, and cardiovascular, skeletal, and gastrointestinal systems. There have been many associated abnormalities reported in the literature. An appreciation of the clinical presentation of Goltz syndrome is important because physicians rely heavily on recognition of key physical characteristics in order to help make a diagnosis. In this report, we summarize the clinical findings observed when we were afforded the unique opportunity to interview and physically examine 19 patients, the largest group of individuals with Goltz syndrome brought together in one place to date. The findings are intended to characterize the orthopedic phenotypic manifestations of Goltz syndrome. This collection of data revealed that the most common orthopedic findings were syndactyly (68%), ectrodactyly (68%), leg length discrepancy (57%), and reduction defects of long bones (52%). Nail irregularities were present in 89% of the patients seen. PMID- 26867037 TI - A Simple Field Method for Assessing Near-Surface Saturated Hydraulic Conductivity. AB - This technical note describes an effective and inexpensive field technique for measuring the saturated hydraulic conductivity of both undisturbed cores and repacked soil samples. The method requires no specialized equipment; everything that is required can be obtained in a hardware store. The method is a straightforward field implementation of the widely used falling-head laboratory analysis directly derived from Darcy's law. As such, it sidesteps the need for empirical assumptions about soil texture and the relationship between saturated and unsaturated flow components which many permeameter-based methods rely upon. The method is shown to produce results that are consistent with K values obtained elsewhere in the same homogeneous sand formation. Furthermore, the proposed method is useful for measuring hydraulic conductivity in drill cuttings obtained from direct push or auguring drill techniques, which cannot be done with any other field method. The range of hydraulic conductivity values that this test is appropriate for is on the order of 1E - 7 m/s to 1E - 3 m/s. PMID- 26867034 TI - JNK/SAPK Signaling Is Essential for Efficient Reprogramming of Human Fibroblasts to Induced Pluripotent Stem Cells. AB - Reprogramming of somatic cells to the phenotypic state termed "induced pluripotency" is thought to occur through three consecutive stages: initiation, maturation, and stabilisation. The initiation phase is stochastic but nevertheless very important as it sets the gene expression pattern that permits completion of reprogramming; hence a better understanding of this phase and how this is regulated may provide the molecular cues for improving the reprogramming process. c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPKs) are stress activated MAPK kinases that play an essential role in several processes known to be important for successful completion of the initiation phase such as cellular proliferation, mesenchymal to epithelial transition (MET) and cell cycle regulation. In view of this, we postulated that manipulation of this pathway would have significant impacts on reprogramming of human fibroblasts to induced pluripotent stem cells. Accordingly, we found that key components of the JNK/SAPK signaling pathway increase expression as early as day 3 of the reprogramming process and continue to rise in reprogrammed cells throughout the initiation and maturation stages. Using both chemical inhibitors and RNA interference of MKK4, MKK7 and JNK1, we tested the role of JNK/SAPK signaling during the initiation stage of neonatal and adult fibroblast reprogramming. These resulted in complete abrogation of fully reprogrammed colonies and the emergence of partially reprogrammed colonies which disaggregated and were lost from culture during the maturation stage. Inhibition of JNK/SAPK signaling resulted in reduced cell proliferation, disruption of MET and loss of the pluripotent phenotype, which either singly or in combination prevented establishment of pluripotent colonies. Together these data provide new evidence for an indispensable role for JNK/SAPK signaling to overcome the well-established molecular barriers in human somatic cell induced reprogramming. Stem Cells 2016;34:1198-1212. PMID- 26867038 TI - Is spending money on others good for your heart? AB - OBJECTIVE: Does spending money on others (prosocial spending) improve the cardiovascular health of community-dwelling older adults diagnosed with high blood pressure? METHOD: In Study 1, 186 older adults diagnosed with high blood pressure participating in the Midlife in the U.S. Study (MIDUS) were examined. In Study 2, 73 older adults diagnosed with high blood pressure were assigned to spend money on others or to spend money on themselves. RESULTS: In Study 1, the more money people spent on others, the lower their blood pressure was 2 years later. In Study 2, participants who were assigned to spend money on others for 3 consecutive weeks subsequently exhibited lower systolic and diastolic blood pressure compared to participants assigned to spend money on themselves. The magnitude of these effects was comparable to the effects of interventions such as antihypertensive medication or exercise. CONCLUSIONS: Together, these findings suggest that spending money on others shapes cardiovascular health, thereby providing a pathway by which prosocial behavior improves physical health among at risk older adults. (PsycINFO Database Record PMID- 26867039 TI - The role of caregiver social support, depressed mood, and perceived stress in changes in pediatric secondhand smoke exposure and asthma functional morbidity following an asthma exacerbation. AB - OBJECTIVE: Caregiver depressed mood and stress are associated with increased child asthma functional morbidity (AFM) and secondhand smoke exposure (SHSe), whereas social support (SS) reduces risk. This study extends previous literature by examining (1) longitudinal patterns of pediatric AFM and SHSe and (2) how caregiver stress, depressed mood, and SS are related to child SHSe and AFM changes. METHOD: Participants were 334 caregivers who smoked, had a child with asthma, and were enrolled in a smoking cessation induction/asthma intervention. SHSe and AFM were measured at baseline and 4, 6, and 12 months. All measures were caregiver self-report. We used an autoregressive latent trajectory model to examine the intercept, linear, and quadratic growth factors and autoregressive and cross-lagged effects of SHSe and AFM. RESULTS: After an asthma exacerbation, decreases in child AFM and SHSe were followed by respective increases over time. Child SHSe at 4 months and 6 months predicted subsequent child AFM. Autoregressive paths were significant for only AFM. Higher baseline caregiver depressed mood and stress predicted higher baseline child AFM but not other growth factors. Higher baseline caregiver self-esteem SS was associated with only lower baseline child AFM and fewer increases in AFM across time. Exploratory analyses indicated higher baseline caregiver depressed mood and stress were associated with less-favorable changes in child SHSe and AFM. CONCLUSIONS: Caregiver depressed mood, stress, and SS should be considered when addressing pediatric SHSe and AFM. Caregiver support may be needed to maintain intervention gains. (PsycINFO Database Record PMID- 26867040 TI - Dispositional emotional expressivity, cancer-specific coping, and distress in socioeconomically-disadvantaged Latinas. AB - OBJECTIVE: Coping processes directed toward avoiding and approaching stressor related thoughts and emotions predict psychological adjustment. However, few studies have examined how the relationship between dispositional emotional tendencies and stressor-specific coping affects outcomes. The aim of the current study was to examine the association of dispositional emotional expressivity (i.e., the propensity to experience and express emotions strongly) with cancer specific coping through avoidance and emotional approach to predict intrusive thoughts and depressive symptoms in Latinas with breast cancer. METHOD: Recently diagnosed Latina breast cancer patients receiving treatment completed standardized assessments via interview at 2 time points: within 18 months of diagnosis (Time 1; N = 95) and 3 months later (Time 2; N = 79). RESULTS: Most women were immigrants (93%), reported a combined household income of $20,000 or less (75%), did not graduate from high school (59%), and primarily spoke Spanish (88%). In path analyses, more recent immigration was associated with greater dispositional expressivity, which in turn was associated with coping with the cancer experience using both greater avoidance and emotional approach strategies. Only avoidance-oriented strategies predicted an increase in intrusive thoughts at 3 months. No significant effects on depressive symptoms were observed. CONCLUSIONS: Findings suggest that Latina breast cancer patients who have a propensity to experience and express emotions strongly may be initially overwhelmed by their cancer-related emotions and consequently turn to avoidance oriented and emotional approach strategies to cope with their diagnosis. Avoidance-oriented coping in turn may uniquely predict an increase in cancer related intrusive thoughts 3 months later. (PsycINFO Database Record PMID- 26867041 TI - Fatigue and mood among people with arthritis: Carry-over across the day. AB - OBJECTIVE: The present study examined the within-day relationship between fatigue and positive and negative mood among adults with rheumatoid arthritis (RA) or osteoarthritis (OA). METHOD: A sample of 142 adults-70 with RA and 72 with OA (67.6% women, 32.4% men)-completed daily diaries during 4 fixed time windows per day for 7 days. In each diary, participants reported fatigue, pain, happiness, and frustration. Multilevel modeling tested the temporal patterns in fatigue across the day and the lagged associations between fatigue and subsequent mood (and vice versa). RESULTS: Fatigue showed a midmorning dip followed by a linear rise in the afternoon and evening. Higher fatigue earlier in the day predicted subsequently lower happiness and higher frustration. Higher frustration-but not happiness-predicted subsequently worse fatigue. These within-day patterns were significant even when controlling for daily sleep quality, daily physical activity, diagnosis, age, gender, anxiety, depression, and disability. CONCLUSIONS: There was a unidirectional effect of fatigue on subsequent happiness and a bidirectional relationship between fatigue and frustration within the same day for adults with RA or OA. These findings inform interventions for the management of mood and fatigue throughout the day and suggest that addressing fatigue could improve mood, and that addressing sources of frustration could improve fatigue among people with arthritis. PMID- 26867042 TI - Affective forecasting and medication decision making in breast-cancer prevention. AB - OBJECTIVE: Over 2 million American women at elevated risk for breast cancer are eligible to take chemoprevention medications such as tamoxifen and raloxifene, which can cut in half the risk of developing breast cancer, but which also have a number of side effects. Historically, very few at-risk women have opted to use chemoprevention medications. Affective forecasting theory suggests that people may avoid these medications if they expect taking them to increase their health related stress. METHOD: After receiving an individually tailored decision aid that provided personalized information about the risks and benefits of these medications, 661 women at elevated risk of breast cancer were asked to make 3 affective forecasts, predicting what their level of health-related stress would be if they took tamoxifen, raloxifene, or neither medication. They also completed measures of decisional preferences and intentions, and at a 3-month follow-up, reported on whether or not they had decided to use either medication. RESULTS: On the affective forecasting items, very few women (<10%) expected the medications to reduce their health-related stress, relative to no medication at all. Participants with more negative affective forecasts about taking a chemoprevention medication expressed lower preferences and intentions for using the medications (Cohen's ds from 0.74 to 0.79) and were more likely to have opted against using medication at follow-up (OR range = 1.34-2.66). CONCLUSION: These findings suggest that affective forecasting may explain avoidance of breast cancer chemoprevention medications. They also highlight the need for more research aimed at integrating emotional content into decision aids. (PsycINFO Database Record PMID- 26867044 TI - Feeling older and risk of hospitalization: Evidence from three longitudinal cohorts. AB - OBJECTIVE: Subjective age is a biopsychosocial marker of aging with a range of health-related implications. Using 3 longitudinal samples, this study examined whether subjective age predicts hospitalization among older adults. METHOD: Participants were adults aged from 24 to 102 years old, drawn from the 1995-1996 and 2004-2005 waves of the Midlife in the United States Survey (MIDUS, N = 3209), the 2008 and 2012 waves of the Health and Retirement Study (HRS, N = 3779), and the 2011 and 2013 waves of the National Health and Aging Trends Study (NHATS, N = 3418). In each sample, subjective age and covariates were assessed at baseline and hospitalization was assessed at follow-up. RESULTS: Consistent across the 3 samples, participants who felt subjectively older at baseline had an increased likelihood of hospitalization (combined effect size: 1.17, 95% CI 1.11-1.23), controlling for age, sex, race, and education. Further adjusting for disease burden and depression reduced the magnitude of the association between subjective age and hospitalization in the 3 samples, but it remained significant in the MIDUS and HRS. CONCLUSION: This study provides consistent evidence that subjective age predicts incident hospitalization. Subjective age assessment can help identify individuals at greater risk of hospitalization, who may benefit from prevention and intervention efforts. (PsycINFO Database Record PMID- 26867043 TI - Depressive symptoms and responses to cigarette pack warning labels among Mexican smokers. AB - OBJECTIVE: We examine whether having depressive symptoms (DS) is associated with different responses to cigarette package health warning labels (HWLs) before and after the implementation of pictorial HWLs in Mexico. METHOD: We analyze data from adult smokers from Wave 4 and Wave 5 (n = 1,340) of the International Tobacco Control Policy Evaluation Project in Mexico. Seven Center for Epidemiological Studies Depression Scale (CES-D) items assessed DS, with scores >=7 indicating elevated DS. Outcomes included: attention to HWLs, cognitive responses to HWLs, tobacco constituents awareness, putting off smoking due to HWLs, avoidance of HWLs, and awareness of telephone support for cessation (i.e., quitlines). Mixed effects models were used to assess main and interactive effects of DS and time (i.e., survey wave) on each outcome. RESULTS: All HWL responses increased over time, except putting off smoking. Statistically significant interactions were found between DS and time for models of tobacco constituents awareness (b = -0.36, SE = 0.15, p = .022), putting off smoking (OR = 0.41, 95% CI [0.25, 0.66]), avoidance of HWLs (OR = 1.84, 95% CI [1.03, 3.29]), and quitline awareness (OR = 0.35, 95% CI [0.21, 0.56]). Compared to smokers with low DS, smokers with elevated DS reported stronger HWL responses at baseline; however, HWL responses increased over time among smokers with low DS, whereas HWL responses showed little or no change among smokers with elevated DS. DISCUSSION: Population-level increases in HWL responses after pictorial HWLs were introduced in Mexico appeared mostly limited to smokers with low DS. In general, however, smokers with elevated DS reported equivalent or stronger HWL responses than smokers with low DS. PMID- 26867047 TI - Fostering liver living donor liver transplantation. AB - PURPOSE OF REVIEW: The review discusses issues pertinent to fostering professional and public interest in living donor liver transplantation. We discuss practices that we have adopted at our center, issues that have arisen and provide suggestions to expand live donor transplantation. RECENT FINDINGS: To bridge the gap between the current supply and demand of deceased donor organs, the transplant program in Toronto established the busiest live donor liver transplant program in the western world. To date, we have performed 664 live liver donor procedures with no donor deaths and excellent recipient and donor outcomes. To foster and grow live donation, we established a strong culture supporting live donation; hired a full-time, dedicated team of individuals to support the live donor program; obtained financial support for donors through a partnership agreement with the Trillium Gift of Life Network; developed linkages with the media, community service groups and the general public; generated patient education materials; and established a website. SUMMARY: With the present and future trends of deceased donation worldwide, we anticipate that live liver donation will remain an important option to fully meet the needs of patients requiring liver transplantation for the foreseeable future. PMID- 26867045 TI - Enhancing physical function in HIV-infected older adults: A randomized controlled clinical trial. AB - OBJECTIVE: HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. METHOD: In total, 67 community-dwelling HOA with mild-to moderate functional limitations were randomized to 1 of 2 groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. RESULTS: The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p < .05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared with the control group (p < .05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p < .05). CONCLUSION: Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. (PsycINFO Database Record PMID- 26867048 TI - Acute alcoholic hepatitis as indication for liver transplantation. AB - PURPOSE OF REVIEW: Until recently, severe acute alcoholic hepatitis that is refractory to medical therapy was a disease with extremely high mortality and no viable treatment options. A landmark trial of early liver transplantation in highly selected patients demonstrated a clear survival benefit and favorable posttransplant outcomes. Since then, new findings regarding medical therapy for alcoholic hepatitis, outcomes of early transplant, and ethical considerations as well as public perception of this intervention have been published. RECENT FINDINGS: Glucocorticoids remain the best initial medical therapy for severe acute alcoholic hepatitis, but liver transplantation can be an acceptable and effective therapy for those who fail to respond to steroids. Recurrence of harmful drinking is a valid concern, and has been observed in long-term follow-up of patients transplanted for alcoholic liver disease. Public perception of early liver transplant for severe acute alcoholic hepatitis is overall positive. SUMMARY: Liver transplantation for refractory severe acute alcoholic hepatitis is a life-saving intervention and should be judiciously employed in highly selected individuals who are at low risk of recidivism. PMID- 26867046 TI - OPTIMA prelim: a randomised feasibility study of personalised care in the treatment of women with early breast cancer. AB - BACKGROUND: There is uncertainty about the chemotherapy sensitivity of some oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2) negative breast cancers. Multiparameter assays that measure the expression of several tumour genes simultaneously have been developed to guide the use of adjuvant chemotherapy for this breast cancer subtype. The assays provide prognostic information and have been claimed to predict chemotherapy sensitivity. There is a dearth of prospective validation studies. The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) is the feasibility phase of a randomised controlled trial (RCT) designed to validate the use of multiparameter assay directed chemotherapy decisions in the NHS. OBJECTIVES: OPTIMA prelim was designed to establish the acceptability to patients and clinicians of randomisation to test-driven treatment assignment compared with usual care and to select an assay for study in the main RCT. DESIGN: Partially blinded RCT with adaptive design. SETTING: Thirty five UK hospitals. PARTICIPANTS: Patients aged >= 40 years with surgically treated ER-positive HER2-negative primary breast cancer and with 1-9 involved axillary nodes, or, if node negative, a tumour at least 30 mm in diameter. INTERVENTIONS: Randomisation between two treatment options. Option 1 was standard care consisting of chemotherapy followed by endocrine therapy. In option 2, an Oncotype DX((r)) test (Genomic Health Inc., Redwood City, CA, USA) performed on the resected tumour was used to assign patients either to standard care [if 'recurrence score' (RS) was > 25] or to endocrine therapy alone (if RS was <= 25). Patients allocated chemotherapy were blind to their randomisation. MAIN OUTCOME MEASURES: The pre-specified success criteria were recruitment of 300 patients in no longer than 2 years and, for the final 150 patients, (1) an acceptance rate of at least 40%; (2) recruitment taking no longer than 6 months; and (3) chemotherapy starting within 6 weeks of consent in at least 85% of patients. RESULTS: Between September 2012 and 3 June 2014, 350 patients consented to join OPTIMA prelim and 313 were randomised; the final 150 patients were recruited in 6 months, of whom 92% assigned chemotherapy started treatment within 6 weeks. The acceptance rate for the 750 patients invited to participate was 47%. Twelve out of the 325 patients with data (3.7%, 95% confidence interval 1.7% to 5.8%) were deemed ineligible on central review of receptor status. Interviews with researchers and recordings of potential participant consultations made as part of the integral qualitative recruitment study provided insights into recruitment barriers and led to interventions designed to improve recruitment. Patient information was changed as the result of feedback from three patient focus groups. Additional multiparameter analysis was performed on 302 tumour samples. Although Oncotype DX, MammaPrint((r))/BluePrint((r)) (Agendia Inc., Irvine, CA, USA), Prosigna((r)) (NanoString Technologies Inc., Seattle, WA, USA), IHC4, IHC4 automated quantitative immunofluorescence (AQUA((r))) [NexCourse BreastTM (Genoptix Inc. Carlsbad, CA, USA)] and MammaTyper((r)) (BioNTech Diagnostics GmbH, Mainz, Germany) categorised comparable numbers of tumours into low- or high-risk groups and/or equivalent molecular subtypes, there was only moderate agreement between tests at an individual tumour level (kappa ranges 0.33 0.60 and 0.39-0.55 for tests providing risks and subtypes, respectively). Health economics modelling showed the value of information to the NHS from further research into multiparameter testing is high irrespective of the test evaluated. Prosigna is currently the highest priority for further study. CONCLUSIONS: OPTIMA prelim has achieved its aims of demonstrating that a large UK clinical trial of multiparameter assay-based selection of chemotherapy in hormone-sensitive early breast cancer is feasible. The economic analysis shows that a trial would be economically worthwhile for the NHS. Based on the outcome of the OPTIMA prelim, a large-scale RCT to evaluate the clinical effectiveness and cost-effectiveness of multiparameter assay-directed chemotherapy decisions in hormone-sensitive HER2 negative early breast would be appropriate to take place in the NHS. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42400492. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 10. See the NIHR Journals Library website for further project information. The Government of Ontario funded research at the Ontario Institute for Cancer Research. Robert C Stein received additional support from the NIHR University College London Hospitals Biomedical Research Centre. PMID- 26867050 TI - Multivisceral transplantation for diffuse splanchnic venous thrombosis. AB - PURPOSE OF REVIEW: The development of diffuse splanchnic venous thrombosis continues to be a challenging undertaking for patients waiting for liver transplantation, requiring the utilization of highly complex surgical techniques. The aim of this article is to review the status of multivisceral transplantation (MVT) in the setting of diffuse portomesenteric thrombosis. RECENT FINDINGS: Even though many anatomical reconstructions of the venous system have been proposed to revascularize the transplanted liver, there are only few articles describing the use of these techniques. Here we describe a succinct review of these alternatives with emphasis on MVT. SUMMARY: MVT is a complex procedure; however, it is the only one capable of reestablishing the venous anatomy and physiology of the abdominal cavity, resolving completely the effects of portal hypertension and the baseline disease. PMID- 26867051 TI - Who comes first? PMID- 26867049 TI - Generation of an artificial intestine for the management of short bowel syndrome. AB - PURPOSE OF REVIEW: This article discusses the current state of the art in artificial intestine generation in the treatment of short bowel syndrome. RECENT FINDINGS: Short bowel syndrome defines the condition in which patients lack sufficient intestinal length to allow for adequate absorption of nutrition and fluids, and thus need parenteral support. Advances toward the development of an artificial intestine have improved dramatically since the first attempts in the 1980s, and the last decade has seen significant advances in understanding the intestinal stem cell niche, the growth of complex primary intestinal stem cells in culture, and fabrication of the biomaterials that can support the growth and differentiation of these stem cells. There has also been recent progress in understanding the role of the microbiota and the immune cells on the growth of intestinal cultures on scaffolds in animal models. Despite recent progress, there is much work to be done before the development of a functional artificial intestine for short bowel syndrome is successfully achieved. SUMMARY: Continued concerted efforts by cell biologists, bioengineers, and clinician-scientists will be required for the development of an artificial intestine as a clinical treatment modality for short bowel syndrome. PMID- 26867052 TI - Stack the odds in favor of newly licensed RNs. PMID- 26867054 TI - Differences in night-time and daytime ambulatory blood pressure when diurnal periods are defined by self-report, fixed-times, and actigraphy: Improving the Detection of Hypertension study. AB - OBJECTIVES: To determine whether defining diurnal periods by self-report, fixed time, or actigraphy produce different estimates of night-time and daytime ambulatory blood pressure (ABP). METHODS: Over a median of 28 days, 330 participants completed two 24-h ABP and actigraphy monitoring periods with sleep diaries. Fixed night-time and daytime periods were defined as 0000-0600 h and 1000-2000 h, respectively. Using the first ABP period, within-individual differences for mean night-time and daytime ABP and kappa statistics for night time and daytime hypertension (systolic/diastolic ABP>=120/70 mmHg and >=135/85 mmHg, respectively) were estimated comparing self-report, fixed-time, or actigraphy for defining diurnal periods. Reproducibility of ABP was also estimated. RESULTS: Within-individual mean differences in night-time systolic ABP were small, suggesting little bias, when comparing the three approaches used to define diurnal periods. The distribution of differences, represented by 95% confidence intervals (CI), in night-time systolic and diastolic ABP and daytime systolic and diastolic ABP was narrowest for self-report versus actigraphy. For example, mean differences (95% CI) in night-time systolic ABP for self-report versus fixed-time was -0.53 (-6.61, +5.56) mmHg, self-report versus actigraphy was 0.91 (-3.61, +5.43) mmHg, and fixed-time versus actigraphy was 1.43 (-5.59, +8.46) mmHg. Agreement for night-time and daytime hypertension was highest for self-report versus actigraphy: kappa statistic (95% CI) = 0.91 (0.86,0.96) and 1.00 (0.98,1.00), respectively. The reproducibility of mean ABP and hypertension categories was similar using each approach. CONCLUSION: Given the high agreement with actigraphy, these data support using self-report to define diurnal periods on ABP monitoring. Further, the use of fixed-time periods may be a reasonable alternative approach. PMID- 26867055 TI - Circulating resistin concentrations are independently associated with aortic pulse wave velocity in a community sample. AB - AIMS: The role of the adipokine, resistin in mediating increases in aortic stiffness is uncertain. We aimed to determine independent relations between circulating resistin concentrations and aortic pulse wave velocity (PWV) and wave reflection in a community-based sample with a high prevalence of untreated hypertension and obesity. METHODS: Plasma resistin, adiponectin, and C-reactive protein concentrations (ELISA); carotid-femoral (aortic) PWV and the aortic reflected wave index (applanation tonometry and SphygmoCor software) were determined in 683 randomly selected participants of African ancestry from SOWETO, South Africa who had never received antihypertensive therapy. RESULTS: Resistin concentrations were not independently associated with office or 24-h (n = 492) blood pressure (BP). In a stepwise regression model with BMI included in the model, age (P < 0.0001), mean arterial pressure (P < 0.0001), plasma resistin concentrations (P < 0.005), female sex (P = 0.01), and creatinine concentrations (P < 0.01) contributed independently to variations in PWV. Independent relations between resistin concentrations and PWV persisted with further adjustments for C reactive protein concentrations (P < 0.005), and the homeostasis model of insulin resistance (P < 0.02). Similar relations were noted with waist circumference rather than BMI in the model. Resistin concentrations were not independently associated with aortic reflected wave index or aortic BP. CONCLUSION: Resistin is independently and directly associated with aortic stiffness and these effects occur beyond BP, insulin resistance, and general inflammation. PMID- 26867053 TI - Parathyroid hormone and the risk of incident hypertension: the Atherosclerosis Risk in Communities study. AB - BACKGROUND: Recent evidence suggests that parathyroid hormone (PTH) has effects on vascular smooth muscle cells, the rennin-angiotensin system and kidney function, but less is known about its role in the development of hypertension. The distribution of serum PTH also varies by race. METHODS AND RESULTS: Therefore, we examined the relation between PTH and incident hypertension and tested for interaction by race among 7504 Atherosclerosis Risk in Communities participants (1264 black, 6240 white, median age 56 years) without initial hypertension in 1990-1992. During a median follow-up of 6 years, 1487 white and 509 black participants developed hypertension. In the overall study population, PTH was not associated with incident hypertension after adjustment for demographics and behavioral risk factors [hazard ratio highest vs. lowest quintiles, 95% confidence interval: 1.11 (0.96-1.28); P for linear trend 0.02]. Although the interaction was not statistically significant (P = 0.60), there was some evidence that the PTH-hypertension association differed by race. Among blacks, PTH was positively associated with incident hypertension, independent of demographics, and behavioral risk factors (P for linear trend 0.003). Among whites, PTH was not associated with hypertension risk. Results were similar when comparing participants with elevated versus nonelevated PTH (>=65 vs. <65 pg/ml): hazard ratio in blacks: 1.24 (1.02-1.54); hazard ratio in whites: 0.95 (0.78 1.16). CONCLUSIONS: In this large community-based cohort, PTH levels, overall, were not independently associated with the risk of hypertension. However, we found some evidence that PTH may be associated with hypertension in blacks. Future research should continue to explore potential race differences in the PTH hypertension association. PMID- 26867057 TI - A cross-sectional study of the effects of beta-blocker therapy on the interpretation of the aldosterone/renin ratio: can dosing regimen predict effect? AB - CONTEXT AND AIM: Aldosterone/renin ratio (ARR) is used as the primary screening tool for primary aldosteronism. Its interpretation is often challenging because of the interference of antihypertensive medication. beta-blocker therapy suppresses renin production by inhibiting beta-adrenergic receptors in the juxtaglomerular apparatus of the kidney and consequently aldosterone secretion (to a lesser extent). Therefore, beta-blocker therapy has the potential to elevate the ARR. The aim of this study was to investigate whether or not the effect of beta-blocker therapy on the ARR could be predicted from the dosing regimen. METHODS: A prospective cross-sectional study was conducted. Participants were stratified into one of four groups (control/low/medium/high) based on the quantity of beta-blocker prescribed. ARR was calculated from renin/aldosterone, measured using two assay systems. RESULTS: Eighty-nine volunteers were recruited to our study. In the control group, zero patients had a positive ARR using plasma renin activity (PRA)/direct renin concentration (DRC). In the low, medium, and high-dose beta-blocker groups between 8-25% of patients demonstrated screen positive ARR results for primary aldosteronism using DRC and PRA. DRC was significantly lower in patients in the medium/high-dose groups and PRA significantly lower in the low/medium/high-dose groups compared with controls. ARR using DRC was significantly higher in the medium/high-dose groups and ARR using PRA was significantly higher in the low/medium/high-dose groups compared with controls. CONCLUSION: Our study suggests that beta-blocker therapy is associated with an increased risk of positive ARR screens for primary aldosteronism irrespective of the dose of beta-blocker prescribed, in patients in whom it is clinically reasonable to expect that primary aldosteronism may be present. PMID- 26867056 TI - Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women. AB - OBJECTIVE: Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: In a cross-sectional study, 20 healthy pregnant women and 20 patients suspected of preeclampsia were included. Plasma and urine was obtained before delivery, and placental biopsies were taken immediately after delivery (mean gestational age: control 39 and preeclampsia 38 weeks). RESULTS: Patients with preeclampsia displayed lower levels of aldosterone in plasma and in spot urine normalized for creatinine (P = 0.0001). Prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances were not different in placental tissue between groups. Prostasin mRNA in placenta correlated directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels did not differ between groups. Activated, arginine 614 (Arg614)-cleaved matriptase was not detectable in placentas. Western blotting showed significant elevated levels of prostasin in urine from preeclamptic patients that correlated with urine albumin. Placenta and plasma prostasin did not correlate to aldosterone or placental weight. CONCLUSION: Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance. PMID- 26867058 TI - Trends in admission blood pressure and stroke outcome in patients with acute stroke and transient ischemic attack in a National Acute Stroke registry. AB - OBJECTIVE: Elevated blood pressure (BP) is common during an acute stroke and is associated with unfavorable outcome. Management of hypertension has improved in recent years. We aimed to evaluate trends in admission BP levels in patients admitted with acute stroke and transient ischemic attack (TIA) over the past decade. METHODS: Data were based on the National Acute Stroke Israeli Registry. The study population comprised 6177 patients, aged at least 18 years admitted for acute stroke (4382 ischemic stroke and 476 intracerebral hemorrhage) or TIA (1227) and had data on BP levels on admission. We studied temporal trends in admission BP and preadmission antihypertensive therapy from 2004 to 2010. RESULTS: Admission SBP (mean +/- SD) in patients with acute stroke decreased from 161 +/- 29 mmHg in 2004 to 153 +/- 28 mmHg in 2010 (P < 0.001). Similar trends were observed for patients with TIA. The use of three or more antihypertensive agents before stroke onset increased from 16.9% in 2004 to 20.0% in 2010 (P = 0.02). In patients with acute stroke, higher admission SBP was associated with increased stroke severity (P < 0.001). Rate of disability at discharge or in hospital death decreased from 71.3% in 2004 to 64.8% in 2010 (P < 0.0001). Admission SBP was associated with disability at discharge or in-hospital death with an adjusted odds ratio (95% confidence interval) of 1.06 (1.04-1.08) per 10 mmHg change in SBP. CONCLUSION: Admission SBP in patients with acute stroke and TIA decreased from 2004 to 2010 and may have contributed to the improved outcome in these patients. PMID- 26867059 TI - Regulation of podoplanin expression by microRNA-29b associates with its antiapoptotic effect in angiotensin II-induced injury of human podocytes. AB - BACKGROUND: Angiotensin (Ang)II is involved in induction of proteinuria, renal injury, and apoptosis and thus a major contributor to the development of chronic kidney disease. Podocytes are of major importance for the pathogenesis of several kidney diseases. Decrease of podoplanin (PDPN) in podocytes and podocyte loss has been associated with the development of proteinuria. Little is known about the regulation and biological function of PDPN in podocytes and its role in AngII mediated kidney damage. Here, we determined the influence of AngII on the expression of PDPN, microRNA (miRNA)-29b and miRNA-497 in human podocytes. Further, we analyzed the impact of small interfering RNA-mediated downregulation of PDPN on AngII-induced apoptosis and viability. Moreover, we characterized the role of miRNA-29b and miRNA-497 in expression regulation of PDPN. METHODS: Cell viability and apoptosis were determined by functional assays. Expression analyses were done via Real-Time PCR and western blot analyses. Dual luciferase assay was performed to characterize miRNA-mediated expression control. RESULTS: AngII increased the expression of miRNA-29b and reduced PDPN. Small interfering RNA mediated downregulation of PDPN increased proapoptotic caspase-3 activation and cytochrome C translocation, whereas cell viability and Akt phosphorylation were reduced in AngII-stimulated podocytes. In contrast to miRNA-497, transfection of cells with miRNA-29b mimics significantly decreased PDPN. Cotransfection of cells with miRNA-29b and a dual luciferase reporter vector decreased the luciferase activity compared with controls. CONCLUSION: These data demonstrate the posttranscriptional control of PDPN expression by miRNA-29b and support a role of PDPN as an antiapoptotic prosurvival factor in AngII-induced injury of human podocytes. PMID- 26867061 TI - Renal sympathetic denervation in treating drug-resistant hypertension in a patient on hemodialysis. AB - A 26-year-old man had an end-stage renal disease because of a neurogenic urinary bladder with a vesicourinary reflux. The first kidney transplant was lost in consequence of chronic allograft nephropathy. Immunosuppressive medication was withdrawn and transplantectomy was performed in November 2010. After transplantectomy, his blood pressure (BP) slowly increased up to 200/100 mmHg. Antihypertensive medication was intensified and a fluid overload was excluded with body composition bioimpedance measurements. Forty-eight-hour ambulatory BP was 180/109 mmHg in the daytime and 178/108 mmHg in the night-time. Bilateral renal denervation (RDN) was performed with a single electrode Symplicity catheter on May 2013. The effect of RDN became evident at the 6 months visit, and all the antihypertensive medicines were withdrawn at 12 months. Fifteen months after RDN, 48-h ambulatory BP was 120/63 mmHg in the daytime and 108/60 mmHg in the night time. The patient was without antihypertensive medication until retransplantation in May 2015. PMID- 26867064 TI - Learning how to ask in ethnography and psychotherapy. AB - To social anthropologists an affinity with psychotherapy lies in the view that this discipline is a social science. Increasingly, social anthropologists offer comments and analyse their own data using psychotherapeutic or psychoanalytic frames of reference. At the same time, a methodological crisis has developed in ethnography. This is a crisis of how to carry out an ethnographic enquiry in a disciplined manner without either claiming to be a detached observer on the one hand or explaining away the subjective experiences of informants or clients with too much interpretation on the other. The aim of this paper is to address this crisis and to suggest ways in which ethnographers can use techniques from one type of psychotherapy, namely systemic or family psychotherapy in order to access social and psychological aspects of the lives of their informants. The paper achieves this by describing systemic psychotherapy and its theoretical foundations in the ethnographic work of Gregory Bateson. It then reviews the mainly medical anthropology literature in which the connection between psychotherapy and anthro pology has been discussed. While this literature has suggested a narrative and a performative approach to ethnographic data and, therefore, to informants, it has not extended the analytic frame to include the ethnographer him/herself within these frames. Clinical case material is presented to demonstrate how such an inclusion is central to the practice of systemic psychotherapy and to show that this type of material is ethnographic. The techniques of double description, hypothesising and circular questioning are described and demonstrated, and it is argued that adapting these to an ethnographic enquiry will enhance the validity of the anthropological project. PMID- 26867065 TI - Predictive genetic testing and the making of the pre-symptomatic person: Prognostic moralities amongst Huntington's-affected families. AB - This paper identifies the emergence of new prognostic categories of genetic health information in contemporary predictive biomedicine. Arguing that pre emptive genetic foreknowledge is linked intimately to the creation of a new classificatory order of "pre-symptomatic" persons, the paper discusses how the "prophetic" revelations of predictive testing technologies transform ordinary persons into moral prognosticators. Case study materials detailing the pre symptomatic illness narratives of three British families affected by a late-onset monogenic condition (Huntington's disease (HD)) are analysed with a view to examining how, as a class of potential "pre-patients", persons are seen to be "ill" before they are "diseased". The clinical burden of "telling" a bad prognosis, similarly, is seen to shift to the moral responsibilities of kin who are obliged to make decisions about when and how to share or withhold genetic information with other potentially "pre-symptomatic" relatives. As genetic tests and treatments are developed and made available for common conditions, not everyone who undergoes genetic testing will face such a bleak prognosis as the HD population. Nonetheless, the narratives presented here illustrate how "the making of the pre-symptomatic person" speaks to some of the more general ethico-cultural dilemmas relating to the politics of pre-emptive health cultures. PMID- 26867062 TI - Sacrum and Coccyx Radiographs Have Limited Clinical Impact in the Emergency Department. AB - OBJECTIVE: The purpose of this study was to determine the yield and clinical impact of sacrum and coccyx radiographs in the emergency department (ED). MATERIALS AND METHODS: Consecutive sacrum and coccyx radiographs obtained in the EDs of four hospitals over a 6-year period were categorized as positive for acute fracture or dislocation, negative, or other. Five follow-up metrics were analyzed: follow-up advanced imaging in the same ED visit, follow-up advanced imaging within 30 days, new analgesic prescriptions, clinic follow-up, and surgical intervention within 60 days. RESULTS: Sacrum and coccyx radiographs from 687 patients (mean age, 48.1 years; 61.6% women and 38.4% men) obtained at level 1 (n = 335) and level-2 (n = 352) trauma centers showed a positivity rate of 8.4% +/- 2.1% (n = 58/687). None of the 58 positive cases had surgical intervention. At the level-1 trauma centers, there was no significant association between sacrum and coccyx radiograph positivity and analgesic prescription or clinical follow-up (p = 0.12; odds ratio [OR], 2.3; 95% CI, 0.81-6.20). At the level-2 trauma centers, 97.1% (n = 34/35) of patients with positive sacrum and coccyx radiographs received analgesic prescriptions or clinical referrals, whereas negative cases were at 82.9% (OR, 7.0; 95% CI, 0.94-52.50). Of all cases, 5.7% (n = 39) and 4.3% (n = 29) had advanced imaging in the same ED visit and within 30 days, respectively. Sacrum and coccyx radiography results had no significant correlation with advanced imaging in the same ED visit (level-1, p = 0.351; level 2, p = 0.179). There was no significant difference in 30-day advanced imaging at the level-1 trauma centers (p = 0.8), but there was at the level-2 trauma centers (p = 0.0493). CONCLUSION: ED sacrum and coccyx radiographs showed a low positivity rate and had no quantifiable clinical impact. We recommend that sacrum and coccyx radiographs be eliminated from ED practice and patients treated conservatively on the basis of clinical parameters. PMID- 26867060 TI - Comparative study of the efficacy of olmesartan/amlodipine vs. perindopril/amlodipine in peripheral blood pressure after missed dose in type 2 diabetes. AB - INTRODUCTION: Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped. OBJECTIVES: The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed. METHODS: In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20-40 mg/amlodipine 5-10 mg or perindopril 4-8 mg/amlodipine 5-10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration. RESULTS: The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination ( 11.7 and -10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group. CONCLUSIONS: The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine. PMID- 26867063 TI - Characteristics of Antithyroid Drug-Induced Agranulocytosis in Patients with Hyperthyroidism: A Retrospective Analysis of 114 Cases in a Single Institution in China Involving 9690 Patients Referred for Radioiodine Treatment Over 15 Years. AB - BACKGROUND: Antithyroid drug (ATD)-induced agranulocytosis is a rare but life threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood. METHOD: Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed. RESULTS: The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (+/-standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 +/- 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 +/- 8.0 mg/day and 253.6 +/- 177.5 mg/day, respectively. ATD induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 +/- 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 +/- 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 +/- 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13). CONCLUSIONS: This largest single-institution study in China shows that ATD induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach. PMID- 26867066 TI - Illusions of controlling the future: Risk and genetic inheritance. AB - The aim of this paper is to analyse the implications of current beliefs that human beings can control the risk of inheriting a genetic disease and influence their present and future health. To accomplish this goal, materials will be drawn from disparate literatures bearing on concepts of probability, risk and genetic inheritance, and on empirical data gathered on cancer survivors and healthy persons with a family history of cancer. The concept of risk has been theorised on a grand scale but, as Lupton (1999, Introduction, Risk and Sociological Theory , Cambridge University Press) correctly observes, there has been very little empirical work done on how people experience risk as part of their lived world. In this paper, notions of probabilities and risk will be examined as applied to beliefs in genetic inheritance that are shaped by historical and cultural forces and in turn how they shape people's lives. It will be proposed that the belief that knowledge of one's genetic inheritance can control one's future health and disease is an illusion, and also replicates in part a religious notion of predestination. PMID- 26867067 TI - Cultural politics and clinical competence in Australian health services. AB - Medical competence is demonstrated in multiple ways in clinical settings, and includes technical competence, both in terms of diagnosis and management, and cultural competence, as demonstrated in communication between providers and clients. In cross-cultural contexts, such communication is complicated by interpersonal communication and the social and cultural context. To illustrate this, we present four case studies that illustrate the themes from interviews with immigrant women and refugees from Middle Eastern and Sahel African backgrounds, conducted as part of a study of their reproductive health. In our analysis, we highlight the limitations of conventional models of communication. We illustrate the need for health providers to appreciate the possible barriers of education, ethnicity, religion and gender that can impede communication, and the need to be mindful of broader structural, institutional and inter-cultural factors that affect the quality of the clinical encounter. PMID- 26867068 TI - Recipe knowledge: A tool for understanding some apparently irrational behaviour a,b. AB - What kind of knowledge about illness determines treatment action? The authors explore this question after encountering a paradox in the course of an ethnographic study on Malaria in Tanzania. Why did Tanzanian mothers who knew about the link between degedege --a local term to describe convulsions in children--and malaria still use traditional practices for degedege , even though they would never use these for malaria? Through questionnaires, in-depth interviews, and ethnographic fieldwork, the authors repeatedly elicited and observed seemingly irrational behaviour (for example, urinating over a child, rubbing the child's body with elephant dung, etc.), which their informants could not explain. Informants routinely commented that "this is what we have always done" or "this is what everybody does". In this paper, the authors suggest that Schutz's (1964) idea of "recipe knowledge"--culturally learned formulas that are automatically activated and remain unquestioned as long as nothing unforeseen happens--offers an explanation for such observed behaviour. In the case of degedege , the "recipes" are embedded in a wider schema for action that combines traditional and biomedical practices, and thereby integrate social values of "tradition" and "modernity". These findings reflect on the limitation of classical knowledge transmitted through health messages for behaviour change, and shed light on the role of historical and social context in knowledge construction and therapeutic action. PMID- 26867069 TI - Medical ethics and rites involving blood. AB - Although the discussions in the Netherlands on ritual circumcision of girls, ritual circumcision of boys and hymen construction started more than ten years ago, these discussions about rituals of blood are not connected and offer a range of very diverging views. The significance of this article is to make clear that these diverging views and separated discussions fail to make distinctions. As a result, strategies to achieve abolition of these practices are not well thought through. The objective is to connect and to deepen these discussions by a practical method, starting with the dilemmas aid workers are confronted with. The conclusion is that other issues play a role, the issue of the space we allow others to be different and the manner in which the juxtaposition of "individual versus the group" influences this issue. PMID- 26867070 TI - On humour and pathology: The role of paradox and absurdity for ideological survival. AB - Anthropologically informed approaches to mental health have argued for the importance of examining cultural specificity of mental distress and coping patterns. In an increasingly globalised world, a call has been made within international mental health agendas to pay attention to the particular needs and resources of sub-dominant populations. This paper deals with results from a study carried out with a Mexican community that has engendered a publicly contradictory imagery: a community considered marginal, deviant and multi-pathological, and yet outwittingly resilient and innovative. The goal was to gain an understanding of local patterns of distress and coping--and their encompassing meanings--to guide the orientation of therapeutic interventions. In a first stage, the study involved brief, intensive ethnographic work. This included participant observation, document analysis, application of both structured and semi structured questionnaires, and population-based open-ended interviews. Information about community life, social organisation, value-systems and styles of interaction was collected. In a second phase, analysis of the collected information was followed by the implementation and assessment of community-based family therapy sessions. This report will deal with results from our ethnographic work. Our findings argue that humour-based interactions might serve for psychological and ideological survival in the face of psychosocial stigmatisation. Irony, absurdity and paradox, might be used to contest and transcend, both in thought and in action, the logic of dominant and dichotomous systems of thought where the attributes of pathology are embedded. PMID- 26867074 TI - Improvements in Somatic Complaints Among Individuals With Serious Mental Illness Receiving Treatment in a Psychiatric Hospital. AB - OBJECTIVE: Individuals with serious mental illness (SMI) experience significant comorbid somatic complaints. Little is known about response to integrated inpatient care that addresses psychiatric and general medical needs among individuals with SMI. METHODS: Latent growth curve analyses were used to model somatic symptom trajectories across adult inpatients with SMI (n = 989). The Patient Health Questionnaire-15 (PHQ-15) was administered at admission, every 14 days, and at discharge. RESULTS: Patients evidenced substantial reduction in somatization from admission (mean [standard deviation] = 9.0 [5.2]) to discharge (mean [standard deviation] = 5.2 [4.4]), with large effects (d = 0.83, 95% confidence interval = 0.76-0.90). Results indicate nonlinear improvement in somatic symptoms for 8 weeks of treatment, with greatest symptom reduction occurring during the first weeks of treatment with continued, albeit slowed, improvement until discharge. Initial PHQ-15 scores were lower among men and those who reported regular exercise in the 30 days preceding this hospitalization. In addition, presence of an anxiety disorder or personality disorder at admission; history of trauma, a gastrointestinal disorder, or major medical illness (within the past 3 months); and significant sleep disturbance independently contribute to higher PHQ-15 scores at admission. A substance use disorder and sleep disturbance were associated with greater immediate symptom reduction. CONCLUSIONS: Somatic complaints can be managed in the context of inpatient psychiatric care integrated with 24-hour nursing and internal medicine specialists. Addressing psychiatric impairments, improving sleep, and ensuring abstinence from drugs and alcohol are associated with significant improvement in somatic complaints. PMID- 26867073 TI - Effects of Anxiety on Caloric Intake and Satiety-Related Brain Activation in Women and Men. AB - OBJECTIVE: To test the relationship of anxiety to caloric intake and food cue perception in women and men. METHODS: Fifty-five twins (26 complete, 3 incomplete pairs; 51% women) underwent 2 functional magnetic resonance imaging (fMRI) scans (before and after a standardized meal) and then ate at an ad libitum buffet to objectively assess food intake. State and trait anxiety were assessed using the State-Trait Anxiety Inventory. During the fMRI scans, participants viewed blocks of fattening and nonfattening food images, and nonfood objects. RESULTS: In women, higher trait anxiety was associated with a higher body mass index (BMI) (r = 0.40, p = .010). Trait anxiety was positively associated with kilocalories consumed at the buffet (r = 0.53, p = .005) and percent kilocalories consumed from fat (r = 0.30, p = .006), adjusted for BMI. In within-pair models, which control for shared familial and genetic factors, higher trait anxiety remained associated with kilocalories consumed at the buffet (p = .66, p = .014), but not with BMI. In men, higher state anxiety was related to macronutrient choices, but not to total caloric intake or BMI. FMRI results revealed that women with high trait anxiety did not suppress activation by fattening food cues across brain regions associated with satiety perception after eating a standardized meal (low anxiety, mean difference = -15.4, p < .001; high anxiety, mean difference = 1.53, p = .82, adjusted for BMI). CONCLUSIONS: In women, trait anxiety may promote excess caloric consumption through altered perception of high-calorie environmental food cues, placing women with genetic predispositions toward weight gain at risk of obesity. TRIAL REGISTRATION: Clinicaltrials.govidentifier:NCT02483663. PMID- 26867072 TI - A Biobehavioral Framework to Address the Emerging Challenge of Multimorbidity. AB - Multimorbidity, the co-occurrence of multiple physical or psychological illnesses, is prevalent particularly among older adults. The number of Americans with multiple chronic diseases is projected to increase from 57 million in 2000 to 81 million in 2020. However, behavioral medicine and health psychology, while focusing on the co-occurrence of psychological/psychiatric disorders with primary medical morbidities, have historically tended to ignore the co-occurrence of primary medical comorbidities, such as diabetes and cancer, and their biopsychosocial implications. This approach may hinder our ecologically valid understanding of the etiology, prevention, and treatment for individual patients with multimorbidity. In this selective review, we propose a heuristic behavioral framework for the etiology of multimorbidity. More acknowledgment and systematic research on multiple, co-existing disorders in behavioral medicine are consistent with the biopsychosocial model's emphasis on treating the "whole person," which means not considering any single illness, its symptoms, risk factors, or mechanisms, in isolation. As systems analytics, big data, machine learning, and mixed-model trajectory analyses, among others, come online and become more widely available, we may be able to tackle multimorbidity more holistically, efficiently, and satisfactorily. PMID- 26867075 TI - The Effect of Hostility Reduction on Autonomic Control of the Heart and Vasculature: A Randomized Controlled Trial. AB - OBJECTIVE: Hostility is associated with coronary artery disease. One candidate mechanism may be autonomic nervous system (ANS) dysregulation. In this study, we report the effect of cognitive behavioral treatment on ANS regulation. METHODS: Participants were 158 healthy young adults, high in hostility measured by the Cook-Medley Hostility and Spielberger Trait Anger scales. Participants were also interviewed using the Interpersonal Hostility Assessment Technique. They were randomized to a 12-week cognitive behavioral treatment program for reducing hostility or a wait-list control group. The outcome measures were preejection period, low-frequency blood pressure variability, and high-frequency heart rate variability measured at rest and in response to and recovery from cognitive and orthostatic challenge. Linear-mixed models were used to examine group by session and group by session by period interactions while controlling for sex and age. Contrasts of differential group and session effects were used to examine reactivity and recovery from challenge. RESULTS: After Bonferroni correction, two way and three-way interactions failed to achieve significance for preejection period, low-frequency blood pressure variability, or high-frequency heart rate variability (p > .002), indicating that hostility reduction treatment failed to influence ANS indices. CONCLUSIONS: Reduction in anger and hostility failed to alter ANS activity at rest or in response to or recovery from challenge. These findings raise questions about whether autonomic dysregulation represents a pathophysiological link between hostility and heart disease. PMID- 26867076 TI - Effects of Exercise and Sertraline on Measures of Coronary Heart Disease Risk in Patients With Major Depression: Results From the SMILE-II Randomized Clinical Trial. AB - OBJECTIVE: To assess the effects of supervised and home-based aerobic exercise training, and antidepressant pharmacotherapy (sertraline) on coronary heart disease (CHD) risk factors in a sample of participants with major depressive disorder (MDD). METHODS: The Standard Medical Intervention versus Long-term Exercise (SMILE)-II study randomized 202 adults (153 women, 49 men) diagnosed as having MDD to one of four interventions, each of 4-month duration: supervised exercise, home-based exercise, antidepressant medication (sertraline, 50-200 mg daily), or placebo pill. Patients underwent a structured clinical interview for depression and completed the Hamilton Depression Rating Scale. CHD risk factors included brachial artery flow-mediated dilation, carotid intima-media thickness, serum lipids, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk. RESULTS: Compared with placebo, active treatment of depression (supervised exercise, home-based exercise, sertraline therapy) was associated with an improvement in CHD risk factors (improved flow-mediated dilation [p = .032], reduced progression of intima-media thickness [p = .037], and a reduction in 10 year ASCVD [p = .049]). The active treatments did not differ from each other in their effects on the CHD risk outcomes. CONCLUSIONS: Both exercise and antidepressant medication improved CHD risk factors and lowered ASCVD risk in patients with MDD. Because MDD is associated with increased risk for CHD events, treatment of depression with exercise or sertraline may reduce the risk of developing CHD in patients with MDD. TRIAL REGISTRATION: Clinical Trials Government Identifier: NCT-00331305. PMID- 26867077 TI - Positive Affect and Inflammatory Activity in Breast Cancer Survivors: Examining the Role of Affective Arousal. AB - OBJECTIVE: Given the importance of positive affect and inflammation for well being in cancer survivors, the current study examined the relationship between high- and low-arousal positive affect and inflammation in 186 women who completed treatment of early-stage breast cancer. METHODS: Measures of high- and low arousal positive affect were completed within 3 months after treatment completion (baseline). Plasma markers of inflammation, including soluble tumor necrosis factor receptor type II (sTNF-RII), C-reactive protein (CRP), and interleukin-1 receptor antagonist, were assessed at baseline and 6- and 12-month follow-up assessments. RESULTS: Multilevel modeling analyses showed that high-arousal positive affect was associated with lower levels of sTNF-RII, a marker of TNF activity, at treatment completion and prospectively predicted maintenance of these differences through the 6- and 12-month follow-ups adjusting for biobehavioral confounds (b = -0.055, t(156) = -2.40, p = .018). However, this association was no longer significant when adjusting for fatigue. Exploratory analyses showed that low-arousal positive affect was associated with lower levels of CRP at treatment completion and through the 6- and 12-month follow-ups; this association remained significant after adjusting for fatigue and other confounds (b = -0.217, t(152) = -2.04, p = .043). CONCLUSIONS: The relationship of high arousal positive affect (e.g., "active") with sTNF-RII seems to be driven by the overlap of high-arousal positive affect with fatigue, whereas the relationship of low-arousal positive affect (e.g., "calm") with CRP was independent of fatigue. Future research should consider affective arousal when examining the association of positive affect with inflammation as this facet of positive affect may have important implications for interpretation of results. PMID- 26867080 TI - The Role of Disadvantaged Neighborhood Environments in the Association of John Henryism With Hypertension and Obesity. AB - OBJECTIVE: The John Henryism hypothesis proposes that high-effort, active coping in impoverished, low-resource environments is associated with an increased risk of cardiovascular disease, but a lower risk of disease in a high-resource environment. To test this hypothesis, we examined the association of John Henryism Active Coping (JHAC) with objectively measured neighborhood disadvantages and the relationship to hypertension (including systolic [SBP] and diastolic [DBP] blood pressure) and elevated body mass index (BMI). METHODS: The study included 3105 participants- 39.93% non-Hispanic blacks, 31.66% non-Hispanic whites, and 25.83% Hispanic and 2.58% non-Hispanic other. All participants aged 18 to 92 years were surveyed and underwent a baseline clinical examination as part of the Chicago Community Adult Health Study, from 2001 to 2003. Coping was measured using four items from the JHAC scale, and neighborhood disadvantage was assessed using rater assessments and the US Census data. RESULTS: In multilevel regression models clustered by neighborhood, neither JHAC nor neighborhood disadvantage was significantly associated with hypertension (SBP and DBP) or BMI. However, significant interaction effects of neighborhood disadvantage and JHAC on hypertension (odds ratio [standard error {SE}] = 0.66 [0.11], p = .018), SBP (B [SE] = -2.63 [1.33], p = .048), DBP (B [SE] = -2.08 [0.87], p = .017), and BMI (B [SE] = -1.86 [0.46], p < .001) were found, such that JHAC was related to increases in disadvantaged neighborhoods and decreases in advantaged neighborhoods. CONCLUSIONS: In a large study that modeled objective measures of neighborhood disadvantage, JHAC was associated with increased risk for cardiovascular disease among individuals living in highly disadvantaged neighborhoods which lack resources and opportunities for upward social mobility. This is consistent with the John Henryism hypothesis. PMID- 26867078 TI - The Neurobiology of Giving Versus Receiving Support: The Role of Stress-Related and Social Reward-Related Neural Activity. AB - OBJECTIVES: There is a strong association between supportive ties and health. However, most research has focused on the health benefits that come from the support one receives while largely ignoring the support giver and how giving may contribute to good health. Moreover, few studies have examined the neural mechanisms associated with support giving or how giving support compares to receiving support. METHOD: The current study assessed the relationships: a) between self-reported receiving and giving social support and vulnerability for negative psychological outcomes and b) between receiving and giving social support and neural activity to socially rewarding and stressful tasks. Thirty-six participants (mean [standard deviation] age = 22.36 [3.78] years, 44% female) completed three tasks in the functional magnetic resonance imaging scanner: 1) a stress task (mental arithmetic under evaluative threat), b) an affiliative task (viewing images of close others), and c) a prosocial task. RESULTS: Both self reported receiving and giving social support were associated with reduced vulnerability for negative psychological outcomes. However, across the three neuroimaging tasks, giving but not receiving support was related to reduced stress-related activity (dorsal anterior cingulate cortex [r = -0.27], left [r = 0.28] and right anterior insula [r = -0.33], and left [r = -0.32] and right amygdala [r = -0.32]) to a stress task, greater reward-related activity (left [r = 0.42] and right ventral striatum [VS; r = 0.41]) to an affiliative task, and greater caregiving-related activity (left VS [r = 0.31], right VS [r = 0.31], and septal area [r = 0.39]) to a prosocial task. CONCLUSIONS: These results contribute to an emerging literature suggesting that support giving is an overlooked contributor to how social support can benefit health. PMID- 26867081 TI - Type 2 Diabetes Among People With Posttraumatic Stress Disorder: Systematic Review and Meta-Analysis. AB - OBJECTIVE: To clarify the prevalence and predictors of Type 2 diabetes mellitus (T2DM) in people with posttraumatic stress disorder (PTSD) and where possible compare this to healthy controls. METHODS: We searched major electronic databases until May 2015 for studies reporting T2DM prevalence in people with PTSD. Two independent authors extracted data and completed methodological quality appraisal. A random-effects meta-analysis was used. RESULTS: From 1171 candidate publications after exclusions, nine publications were included (n = 23,396; 28.6% male; mean age = 35-60 years). The overall prevalence of T2DM was 10.0% (95% confidence interval [CI] = 8.1%-12.0%). Subgroup analysis demonstrated that war veterans experience higher prevalence of T2DM (16.3%; 95% CI = 5.2%-31.8%; n studies = 3, n = 473) compared with mixed samples (11.8%; 95% CI = 6.34-18.7, p < .001; n studies = 4, n = 2753). Increasing age (beta = 0.0593, 95% CI = 0.010 0.109, z = 2.34, p = .019), median year of publication (beta = -0.08, 95% CI = 0.14 to -0.03, z = -3.09, p = .002), and a lower percentage of white participants (beta = -3.21, 95% CI = -5.12 to -1.29, z = -2.28, p = .001) predicted prevalence of T2DM. A relative risk meta-analysis comparing controls (n = 125,723) against those with PTSD (n = 23,203) demonstrated a significantly increased risk of T2DM (n studies = 5, relative risk = 1.49, 95% CI = 1.17-1.89, p = .001). CONCLUSIONS: People with PTSD are at a high risk for developing T2DM. The current findings should, however, be interpreted with caution because most studies were based on self-report data. PMID- 26867079 TI - Type D Personality and Coronary Plaque Vulnerability in Patients With Coronary Artery Disease: An Optical Coherence Tomography Study. AB - OBJECTIVE: To investigate the association between Type D personality and higher incidence of major adverse cardiac events, we used in vivo optical coherence tomography (OCT) to evaluate the association between Type D with coronary plaque characteristics. METHODS: A total of 109 patients who had culprit coronary plaque (s) were included in the study. The Type D construct was analyzed using both the categorized and the continuous approaches. Plaque vulnerability of culprit lesions was measured by OCT. RESULTS: After adjusting for demographic and clinical factors, multivariate analysis demonstrated that Type D was associated with lipid plaque (odds ratio [OR] = 4.87, 95% confidence interval [CI] = 1.41 11.14, p = .025), thin cap fibroatheroma (OR = 3.84, 95% CI = 1.36-10.85, p = .011), and fibrous cap thickness (beta = -1.43, standard error = 0.04, p = .001) analyzed by categorical approach. When analyzing Type D as continuous variable, the negative affectivity component was significantly related to plaque vulnerability, including lipid plaque (OR = 3.43, 95% CI = 1.23-9.52, p = .018), thin cap fibroatheroma (OR = 2.20, 95% CI = 1.10-4.40, p = .026), and fibrous cap thickness (beta = -0.05, standard error = 0.02, p = .030), whereas no associations between the negative affectivity by social inhibition interaction term with OCT indices were found. CONCLUSIONS: The results suggest that plaque characteristics in Type D have more features of plaque vulnerability. The negative affectivity component seems to drive the associations between Type D and vulnerable plaques. These findings provide new insights into the mechanism involved in the association between Type D and major adverse cardiac event. PMID- 26867083 TI - Internet-Delivered Cognitive-Behavior Therapy for Tinnitus: A Randomized Controlled Trial. AB - OBJECTIVES: Tinnitus has a substantially negative impact on quality of life in up to 5% of the general population. Internet-based cognitive-behavioral treatment (iCBT) has been shown to be effective in a few trials. The aim of our study was to investigate iCBT for tinnitus by using a randomized controlled trial. METHODS: Patients with severe tinnitus-related distress were randomly assigned to therapist-guided iCBT (n = 62) or to a moderated online discussion forum (n = 62). Standardized self-report measures for tinnitus-related distress (Tinnitus Handicap Inventory, Mini-Tinnitus Questionnaire) and associated symptoms (tinnitus acceptance, anxiety, depression, and insomnia) were assessed at pretreatment and posttreatment, 6-month-, and 1-year follow-up. Clinical significance was assessed with the Reliable Change Index. RESULTS: Multivariate analyses of variance revealed significant main effects for time, group, and interaction in favor of the iCBT group. With regard to tinnitus-related distress, the significant univariate interaction effects (time by group) were supported by large effect sizes (Tinnitus Handicap Inventory: g = 0.83, 95% confidence interval = 0.47-1.20; Mini-Tinnitus Questionnaire: g = 1.08, 95% confidence interval = 0.71-1.64). For the secondary outcomes, significant interactions with small to medium effect sizes were found. Within-group effects for the iCBT, from pretreatment to follow-up, were substantial in regard to tinnitus-related distress (1.38 <= d <= 1.81) and small to large for secondary outcomes (0.39 <= d <= 1.04). CONCLUSIONS: Using a randomized controlled trial design, we replicated prior findings regarding positive effects of Internet-delivered CBT on tinnitus related distress and associated symptoms. Implementing iCBT for tinnitus into regular health care will be an important next step to increase access to treatment for patients with tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT01205919. PMID- 26867082 TI - Linking Daily Stress Processes and Laboratory-Based Heart Rate Variability in a National Sample of Midlife and Older Adults. AB - OBJECTIVE: This study evaluates the associations between people's trait-like patterns of stress in daily life (stressor frequency, perceived stressor severity, affective reactivity to stressors, and negative affect) and laboratory assessed heart rate variability (HRV). METHODS: Data were collected from 909 participants aged 35 to 85 years in the Midlife in the United States Study. Participants reported negative affect and minor stressful events during telephone interviews on 8 consecutive evenings. On a separate occasion, HRV was measured from electrocardiograph recordings taken at rest during a laboratory-based psychophysiology protocol. Regression models were used to evaluate the associations between daily stress processes and three log-transformed HRV indices: standard deviation of R-R intervals (SDRR), root mean square of successive differences (RMSSD), and high-frequency power (high-frequency HRV [HF HRV]). Analyses were adjusted for demographics, body mass index, comorbid conditions, medications, physical activity, and smoking. RESULTS: Stressor frequency was unrelated to HRV (r values ranging from -0.04 to -0.01, p values >.20). However, people with greater perceived stressor severity had lower resting SDRR (fully adjusted B [standard error {SE}] = -0.05 [0.02]), RMSSD (-0.08 [0.03]), and HF-HRV (-0.16 [0.07]). Individuals with more pronounced affective reactivity to stressors also had lower levels of all three HRV indices (SDRR: B [SE] = -0.28 [0.14]; RMSSD: -0.44 [0.19]; HF-HRV: -0.96 [0.37]). Furthermore, aggregated daily negative affect was linked to reduced RMSSD (B [SE] = -0.16 [0.08]) and HF-HRV (-0.35 [0.15]). CONCLUSIONS: In a national sample, individual differences in daily negative affect and responses to daily stressors were more strongly related to cardiovascular autonomic regulation than the frequency of such stressors. PMID- 26867084 TI - Duration of anuria predicts recovery of renal function after acute kidney injury requiring continuous renal replacement therapy. AB - BACKGROUND/AIMS: Little is known regarding the incidence rate of and factors associated with developing chronic kidney disease after continuous renal replacement therapy (CRRT) in acute kidney injury (AKI) patients. We investigated renal outcomes and the factors associated with incomplete renal recovery in AKI patients who received CRRT. METHODS: Between January 2011 and November 2013, 408 patients received CRRT in our intensive care unit. Of them, patients who had normal renal function before AKI and were discharged without maintenance renal replacement therapy (RRT) were included in this study. We examined the incidence of incomplete renal recovery with an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) and factors that increased the risk of incomplete renal recovery after AKI. RESULTS: In total, 56 AKI patients were discharged without further RRT and were followed for a mean of 8 months. Incomplete recovery of renal function was observed in 20 of the patients (35.7%). Multivariate analysis revealed old age and long duration of anuria as independent risk factors for incomplete renal recovery (odds ratio [OR], 1.231; 95% confidence interval [CI], 1.041 to 1.457; p = 0.015 and OR, 1.064; 95% CI, 1.001 to 1.131; p = 0.047, respectively). In a receiver operating characteristic curve analysis, a cut-off anuria duration of 24 hours could predict incomplete renal recovery after AKI with a sensitivity of 85.0% and a specificity of 66.7%. CONCLUSIONS: The renal outcome of severe AKI requiring CRRT was poor even in patients without further RRT. Long-term monitoring of renal function is needed, especially in severe AKI patients who are old and have a long duration of anuria. PMID- 26867085 TI - Series with complete resolution of left atrial appendage thrombi with apixaban in elderly patients. PMID- 26867086 TI - Removal of Trace Pharmaceuticals from Water using coagulation and powdered activated carbon as pretreatment to ultrafiltration membrane system. AB - In this study, the efficacy of water treatment technologies: ultra-filtration (UF), powdered activated carbon (PAC), coagulation (COA) and a combination of these technologies (PAC/UF and COA/UF) to remove target pharmaceuticals (Acetaminophen, Bezafibrate, Caffeine, Carbamazepine, Cotinine, Diclofenac, Gemfibrozil, Ibuprofen, Metoprolol, Naproxen, Sulfadimethoxine, Sulfamethazine, Sulfamethoxazole, Sulfathiazole, Triclosan and Trimethoprim) was investigated. Samples of wastewater from municipal WWTPs were analyzed using direct aqueous injection High Performance Liquid Chromatography with Tandem Quadrupole Mass Spectrometric (LC/MS/MS) detection. On concentration basis, results showed an average removal efficiency of 29%, 50%, and 7%, respectively, for the UF, PAC dosage of 50ppm, and COA dosage of 10ppm. When PAC dosage of 100ppm was used as pretreatment to the combined PAC and UF in-line membrane system, a 90.3% removal efficiency was achieved. The removal efficiency of UF in tandem with COA was 33%, an increase of 4% compared with the single UF treatment. The adsorption effect of PAC combined with the physical separation process of UF revealed the best treatment strategy for removing pharmaceutical contaminant from water. PMID- 26867087 TI - Metacognitive knowledge of olfactory dysfunction in Parkinson's disease. AB - It is well known that patients with Parkinson's Disease (PD) suffer from olfactory impairments, but it is not clear whether patients are aware of their level of deficit in olfactory functioning. Since PD is a neurodegenerative disorder and its progression may be correlated with olfactory loss (Ansari & Johnson, 1975; but see also Doty, Deems, & Stellar, 1988), it is possible that these patients would be subject to metacognitive errors of over-estimation of olfactory ability (White & Kurtz, 2003). Nineteen non-demented PD patients and 19 age-matched controls were each given an objective measure of olfactory identification (the UPSIT, Doty, Shaman, Kimmelman, & Dann, 1984) and a subjective measure involving a questionnaire that asked them to self-rate both their olfactory function generally and their ability to smell each of 20 odors, 12 of which were assessed on the UPSIT. All of the PD patients showed impaired olfactory ability, as did 7 of the controls, according to the UPSIT norms. Self rated and performance-based olfactory ability scores were significantly correlated in controls (r=.49, p=.03) but not in patients with PD (r=.20, p=.39). When the 12 odors common to both the self-rated questionnaire and UPSIT were compared, PD patients were less accurate than controls (t(36)=-4.96, p<.01) at estimating their own ability and the number of over-estimation errors was significantly higher (tone-tailed(29)=1.80, p=.04) in PD patients than in the control group, showing less metacognitive awareness of their ability than controls. These results support the idea that olfactory metacognition is often impaired in PD, as well as in controls recruited for normosmic ability (Wehling, Nordin, Espeseth, Reinvang, & Lundervold, 2011), and indicate that people with PD generally exhibit over-estimation of their olfactory ability at a rate that is higher than controls. These findings imply that PD patients, unaware of their olfactory deficit, are at greater risk of harm normally detected through olfaction, such as smoke or spoiled foods. PMID- 26867088 TI - Frequency tagging yields an objective neural signature of Gestalt formation. AB - The human visual system integrates separate visual inputs into coherently organized percepts, going beyond the information given. A striking example is the perception of an illusory square when physically separated inducers are positioned and oriented in a square-like configuration (illusory condition). This illusory square disappears when the specific configuration is broken, for instance, by rotating each inducer (non-illusory condition). Here we used frequency tagging and electroencephalography (EEG) to identify an objective neural signature of the global integration required for illusory surface perception. Two diagonal inducers were contrast-modulated at different frequency rates f1 and f2, leading to EEG responses exactly at these frequencies over the occipital cortex. Most importantly, nonlinear intermodulation (IM) components (e.g., f1+f2) appeared in the frequency spectrum, and were much larger in response to the illusory square figure than the non-illusory control condition. Since the IMs reflect long-range interactions between the signals from the inducers, these data provide an objective (i.e., at a precise and predicted EEG frequency) signature of neural processes involved in the emergence of illusory surface perception. More generally, these findings help to establish EEG frequency-tagging as a highly valuable approach to investigate the underlying neural mechanisms of subjective Gestalt phenomena in an objective and quantitative manner, at the system level in humans. PMID- 26867089 TI - The effect of different information sources on the anxiety level of pregnant women who underwent invasive prenatal testing. AB - OBJECTIVE: The goal is to explore the effects of age, education, obstetric history and information sources on the (Beck) anxiety levels of pregnant women attending invasive prenatal testing. METHODS: Questionnaire results from 152 pregnant women are utilized. Results are analyzed through an independent samples t-test and a two-step cluster analysis attempting to categorize patients in terms of the chosen variables. RESULTS: t-Tests reveal that age, education and bad obstetric history do not significantly affect anxiety levels. Descriptive statistics indicate that almost 60% of patients feel anxious mostly because of the fear of receiving bad news, followed by the fear of miscarriage, the fear of pain and the fear of hurting the baby. According to the cluster analysis, patients who use doctors or nurses as information sources have significantly lower anxiety levels, while those who do not receive information from any source have the second lowest level of anxiety. Patients who receive information from personal sources (i.e. friends and family) have the highest level of anxiety. Anxiety levels do not change according to test type. CONCLUSIONS: Doctors and nurses should allocate enough time for providing information about prenatal diagnosis before the procedure. This will reduce the anxiety level as well as the felt necessity to search for information from other sources, such as personal or popular which will further increase the level of anxiety. PMID- 26867090 TI - 11-interval PFG pulse sequence for improved measurement of fast velocities of fluids with high diffusivity in systems with short T2(*). AB - Magnetic resonance (MR) was used to measure SF6 gas velocities in beds filled with particles of 1.1 mm and 0.5 mm in diameter. Four pulse sequences were tested: a traditional spin echo pulse sequence, the 9-interval and 13-interval pulse sequence of Cotts et al. (1989) and a newly developed 11-interval pulse sequence. All pulse sequences measured gas velocity accurately in the region above the particles at the highest velocities that could be achieved (up to 0.1 ms(-1)). The spin echo pulse sequence was unable to measure gas velocity accurately in the bed of particles, due to effects of background gradients, diffusivity and acceleration in flow around particles. The 9- and 13-interval pulse sequence measured gas velocity accurately at low flow rates through the particles (expected velocity <0.06 ms(-1)), but could not measure velocity accurately at higher flow rates. The newly developed 11-interval pulse sequence was more accurate than the 9- and 13-interval pulse sequences at higher flow rates, but for velocities in excess of 0.1 ms(-1) the measured velocity was lower than the expected velocity. The increased accuracy arose from the smaller echo time that the new pulse sequence enabled, reducing selective attenuation of signal from faster moving nuclei. PMID- 26867092 TI - Implant Maintenance Should Not Be Forgotten. PMID- 26867091 TI - Dynamic Nuclear Polarization enhanced NMR at 187 GHz/284 MHz using an Extended Interaction Klystron amplifier. AB - A Dynamic Nuclear Polarisation (DNP) enhanced solid-state Magic Angle Spinning (MAS) NMR spectrometer which uses a 187 GHz (corresponding to (1)H NMR frequency of 284 MHz) Extended Interaction Klystron (EIK) amplifier as the microwave source is briefly described. Its performance is demonstrated for a biomolecule (bacteriorhodopsin), a pharmaceutical, and surface functionalised silica. The EIK is very compact and easily incorporated into an existing spectrometer. The bandwidth of the amplifier is sufficient that it obviates the need for a sweepable magnetic field, once set, for all commonly used radicals. The variable power (CW or pulsed) output from the EIK is transmitted to the DNP-NMR probe using a quasi-optic system with a high power isolator and a corrugated waveguide which feeds the microwaves into the DNP-NMR probe. Curved mirrors inside the probe project the microwaves down the axis of the MAS rotor, giving a very efficient system such that maximum DNP enhancement is achieved with less than 3 W output from the microwave source. The DNP-NMR probe operates with a sample temperature down to 90K whilst spinning at 8 kHz. Significant enhancements, in excess of 100 for bacteriorhodopsin in purple membrane (bR in PM), are shown along with spectra which are enhanced by ~25 with respect to room temperature, for both the pharmaceutical furosemide and surface functionalised silica. These enhancements allow hitherto prohibitively time consuming experiments to be undertaken. The power at which the DNP enhancement in bR in PM saturates does not change significantly between 90K and 170 K even though the enhancement drops by a factor of ~11. As the DNP build up time decreases by a factor 3 over this temperature range, the reduction in T1n is presumably a significant contribution to the drop in enhancement. PMID- 26867093 TI - Stress Distribution on Short Implants at Maxillary Posterior Alveolar Bone Model With Different Bone-to-Implant Contact Ratio: Finite Element Analysis. AB - The aim of this study was to evaluate the stress distribution of the short dental implants and bone-to-implant contact ratios in the posterior maxilla using 3 dimensional (3D) finite element models. Two different 3D maxillary posterior bone segments were modeled. Group 1 was composed of a bone segment consisting of cortical bone and type IV cancellous bone with 100% bone-to-implant contact. Group 2 was composed of a bone segment consisting of cortical bone and type IV cancellous bone including spherical bone design and homogenous tubular hollow spaced structures with 30% spherical porosities and 70% bone-to-implant contact ratio. Four-millimeter-diameter and 5-mm-height dental implants were assumed to be osseointegrated and placed at the center of the segments. Lateral occlusal bite force (300 N) was applied at a 25 degrees inclination to the implants long axis. The maximum von Mises stresses in cortical and cancellous bones and implant abutment complex were calculated. The von Mises stress values on the implants and the cancellous bone around the implants of the 70% bone-to-implant contact group were almost 3 times higher compared with the values of the 100% bone-to-implant contact group. For clinical reality, use of the 70% model for finite element analysis simulation of the posterior maxilla region better represents real alveolar bone and the increased stress and strain distributions evaluated on the cortical and cancellous bone around the dental implants. PMID- 26867094 TI - Functionalization of Silyldienol Ethers at the gamma-Position via 2 Silyloxypentadienyl Cations. AB - This report describes Bronsted acid catalyzed de novo synthesis of silyldienol ethers bearing tetrasubstituted double bonds via an intermediacy of 2 silyloxypentadienyl cations. The reactivity of these novel cationic intermediates could be modulated and harnessed toward direct nucleophilic additions regioselectively at the gamma-position to produce highly functionalized silyldienol ethers with tunable control of the resulting double bond geometry. PMID- 26867095 TI - Small RNAs Add Zing to the Zig-Zag-Zig Model of Plant Defenses. AB - Plant small RNAs play important roles in transcriptional and posttranscriptional regulation, with ongoing work demonstrating their functions in diverse pathways. Their roles in defense responses are a topic of active investigation, particularly the rich set of micro (mi)RNAs that target disease resistance genes such as nucleotide binding/leucine-rich repeat (NB-LRR) genes. The miRNA-NB-LRR interactions result in the production of phased, secondary small interfering (phasi)RNAs, and phasiRNAs function in both cis and trans to propagate negative regulatory effects across additional members of the target gene family. Yet, while phasiRNAs have the capacity to trigger targeted decay of specific targets, both in cis and trans, their functional relevance in NB-LRR regulation remains largely a matter of speculation. PMID- 26867096 TI - An inception cohort study assessing the role of pneumococcal and other bacterial pathogens in children with influenza and ILI and a clinical decision model for stringent antibiotic use. AB - BACKGROUND: Influenza-like illness (ILI) is a common reason for paediatric consultations. Viral causes predominate, but antibiotics are used frequently. With regard to influenza, pneumococcal coinfections are considered major contributors to morbidity/mortality. METHODS: In the context of a perennial quality management (QM) programme at the Charite Departments of Paediatrics and Microbiology in collaboration with the Robert Koch Institute, children aged 0-18 years presenting with signs and symptoms of ILI were followed from the time of initial presentation until hospital discharge (Charite Influenza-Like Disease = ChILD Cohort). An independent QM team performed highly standardized clinical assessments using a disease severity score based on World Health Organization criteria for uncomplicated and complicated/progressive disease. Nasopharyngeal and pharyngeal samples were collected for viral reverse transcription polymerase chain reaction and bacterial culture/sensitivity and MaldiTOF analyses. The term 'detection' was used to denote any evidence of viral or bacterial pathogens in the (naso)pharyngeal cavity. With the ChILD Cohort data collected, a standard operating procedure (SOP) was created as a model system to reduce the inappropriate use of antibiotics in children with ILI. Monte Carlo simulations were performed to assess cost-effectiveness. RESULTS: Among 2,569 ChILD Cohort patients enrolled from 12/2010 to 04/2013 (55% male, mean age 3.2 years, range 0 18, 19% >5 years), 411 patients showed laboratory-confirmed influenza, with bacterial co-detection in 35%. Influenza and pneumococcus were detected simultaneously in 12/2,569 patients, with disease severity clearly below average. Pneumococcal vaccination rates were close to 90%. Nonetheless, every fifth patient was already on antibiotics upon presentation; new antibiotic prescriptions were issued in an additional 20%. Simulation of the model SOP in the same dataset revealed that the proposed decision model could have reduced the inappropriate use of antibiotics significantly (P<0.01) with an incremental cost effectiveness ratio of -99.55?. CONCLUSIONS: Physicians should be made aware that in times of pneumococcal vaccination the prevalence and severity of influenza infections complicated by pneumococci may decline. Microbiological testing in combination with standardized disease severity assessments and review of vaccination records could be cost-effective, as well as promoting stringent use of antibiotics and a personalized approach to managing children with ILI. PMID- 26867097 TI - Dissolved radon and uranium in groundwater in a potential coal seam gas development region (Richmond River Catchment, Australia). AB - The extraction of unconventional gas resources such as shale and coal seam gas (CSG) is rapidly expanding globally and often prevents the opportunity for comprehensive baseline groundwater investigations prior to drilling. Unconventional gas extraction often targets geological layers with high naturally occurring radioactive materials (NORM) and extraction practices may possibly mobilise radionuclides into regional and local drinking water resources. Here, we establish baseline groundwater radon and uranium levels in shallow aquifers overlying a potential CSG target formation in the Richmond River Catchment, Australia. A total of 91 groundwater samples from six different geological units showed highly variable radon activities (0.14-20.33 Bq/L) and uranium levels (0.001-2.77 MUg/L) which were well below the Australian Drinking Water Guideline values (radon; 100 Bq/L and uranium; 17 MUg/L). Therefore, from a radon and uranium perspective, the regional groundwater does not pose health risks to consumers. Uranium could not explain the distribution of radon in groundwater. Relatively high radon activities (7.88 +/- 0.83 Bq/L) in the fractured Lismore Basalt aquifer coincided with very low uranium concentrations (0.04 +/- 0.02 MUg/L). In the Quaternary Sediments aquifers, a positive correlation between U and HCO3(-) (r(2) = 0.49, p < 0.01) implied the uranium was present as uranyl carbonate complexes. Since NORM are often enriched in target geological formations containing unconventional gas, establishing radon and uranium concentrations in overlying aquifers comprises an important component of baseline groundwater investigations. PMID- 26867099 TI - Concentrations of iodine isotopes ((129)I and (127)I) and their isotopic ratios in aerosol samples from Northern Germany. AB - New data about (129)I, (127)I concentrations and their isotopic ratios in aerosol samples from the trace survey station of the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Northern Germany, are presented and discussed in this paper. The investigated samples were collected on a weekly basis during the years 2011 to 2013. Iodine was extracted from aerosol filters using a strong basic solution and was separated from the matrix elements with chloroform and was analysed by accelerator mass spectrometry (AMS) for (129)I and by inductively coupled plasma mass spectrometry (ICP-MS) for (127)I. The concentrations of (127)I and (129)I in aerosol filters ranged from 0.31 to 3.71 ng m(-3) and from 0.06 to 0.75 fg m(-3), respectively. The results of (129)I/(127)I isotopic ratios were in the order 10(-8) to 10(-7). The (129)I originated directly from gaseous emissions and indirectly from liquid emissions (via sea spray) from the reprocessing plants in Sellafield and La Hague. In comparison with the results of (131)I after the Fukushima accident, no contribution of (129)I from this accident was detectable in Central Europe due to the high background originating from the (129)I releases of the European reprocessing plants. (129)I atmospheric activity concentrations were compared with those of an anthropogenic radionuclide ((85)Kr). We did not find any correlation between (129)I and (85)Kr, both having nuclear reprocessing plant as the main source. PMID- 26867098 TI - Analysis of spectra from portable handheld gamma-ray spectrometry for terrain comparative assessment. AB - Geological characteristics can have impacts on societal development by, e.g., geotechnical issues and radiological hazard levels. Due to urban sprawl, there is an increasing need for detailed geological assessment. In this work are analysed data from portable handheld gamma-ray spectra (K, eU and eTh) obtained in granitic and Silurian metaclastic outcrops as well as in an profile, roughly N-S, on soil covered terrains transecting a mapped contact between these rock types (the profile's northern extremity is at locations mapped as granite). Estimations from gamma-ray spectra were studied by univariate and multivariate analyses. K, eU and eTh values were higher on granite in relation to Silurian metaclastic rocks. The northern extremity of the profile showed clearly higher contents of eTh and this contrast was supported by univariate statistical tools (normality plot and Wilk-Shapiro test; boxplots). A ternary plot with the contribution of the elements to gamma-ray absorbed dose showed the separation of granite from Silurian metaclastic rocks with the former being nearer the eTh vertex. The points in the northern extremity of the profile are nearer the eTh vertex than the other points on the profile. These visual suggestions were supported by hierarchical cluster analysis, which was able to differentiate between granite and metaclastic outcrops and separate portions of the profile located on different terrains. Portable gamma-ray spectrometry showed, hence, the potential to distinguish granite and metaclastic terrains at a scale useful for engineering works. These results can also be useful for a first comparative zoning of radiological hazards (which are higher for granite). PMID- 26867100 TI - Alternative Fuel Vehicle Adoption Increases Fleet Gasoline Consumption and Greenhouse Gas Emissions under United States Corporate Average Fuel Economy Policy and Greenhouse Gas Emissions Standards. AB - The United States Corporate Average Fuel Economy (CAFE) standards and Greenhouse Gas (GHG) Emission standards are designed to reduce petroleum consumption and GHG emissions from light-duty passenger vehicles. They do so by requiring automakers to meet aggregate criteria for fleet fuel efficiency and carbon dioxide (CO2) emission rates. Several incentives for manufacturers to sell alternative fuel vehicles (AFVs) have been introduced in recent updates of CAFE/GHG policy for vehicles sold from 2012 through 2025 to help encourage a fleet technology transition. These incentives allow automakers that sell AFVs to meet less stringent fleet efficiency targets, resulting in increased fleet-wide gasoline consumption and emissions. We derive a closed-form expression to quantify these effects. We find that each time an AFV is sold in place of a conventional vehicle, fleet emissions increase by 0 to 60 t of CO2 and gasoline consumption increases by 0 to 7000 gallons (26,000 L), depending on the AFV and year of sale. Using projections for vehicles sold from 2012 to 2025 from the Energy Information Administration, we estimate that the CAFE/GHG AFV incentives lead to a cumulative increase of 30 to 70 million metric tons of CO2 and 3 to 8 billion gallons (11 to 30 billion liters) of gasoline consumed over the vehicles' lifetimes - the largest share of which is due to legacy GHG flex-fuel vehicle credits that expire in 2016. These effects may be 30-40% larger in practice than we estimate here due to optimistic laboratory vehicle efficiency tests used in policy compliance calculations. PMID- 26867101 TI - New Luminescent Polynuclear Metal Complexes with Anticancer Properties: Toward Structure-Activity Relationships. AB - A series of new heterodinuclear luminescent complexes with two different organic ligands have been synthesized and characterized. A luminescent Ru(II)(polypyridine) moiety and a metal-based anticancer fragment (AuCl, (p cymene)RuCl2, (p-cymene)OsCl2, (Cp*)RhCl2, or Au-thioglucose) are the two general features of these complexes. All of the bimetallic compounds have been evaluated for their antiproliferative properties in vitro in human cancer cell lines. Only the complexes containing an Au(I) fragment exhibit antiproliferative activity in the range of cisplatin or higher. The photophysical and electrochemical properties of the bimetallic species have been investigated, and fluorescence microscopy experiments have been performed successfully. The most promising bimetallic cytotoxic complexes (i.e., with the Au-thioglucose scaffold) have shown to be easily taken up by cancer cells at 37 degrees C in the cytoplasm or in specific organelles. Interestingly, experiments repeated at 4 degrees C showed no uptake of the bimetallic species inside cells, which confirms involvement of active transport processes. To evaluate the role of glucose transporters in the cell uptake of the gold complexes, inhibition of the GluT-1 (glucose transporter isoform with high level of expression in cancer cells) was achieved, showing only scarce influence on the compounds' uptake. Finally, the observed absence of interactions with nucleic acid model structures suggests that the gold compounds may have different intracellular targets with respect to cisplatin. PMID- 26867102 TI - The Synthesis of Multifunctionalized 1,3-Oxazin-4-ones from Donor-Acceptor Cyclopropanes. AB - A series of electronically diverse imines were found to readily react with various donor-acceptor cyclopropyl acid chlorides, with complete regioselectivity, to form 1,3-oxazin-4-ones in moderate yields (25-48% over two steps). Select oxazinones underwent a base induced rearrangement to afford the corresponding cycloheptene-fused oxazinones in good yields (up to 70%). PMID- 26867104 TI - Why victims of undermining at work become perpetrators of undermining: An integrative model. AB - We develop and test an integrative model explaining why victims of workplace social undermining become perpetrators of undermining. Conceptualizing social undermining as a norm-violating and a resource-depleting experience, we theorize that undermining victimization lowers interpersonal justice perceptions and depletes self-regulatory resources, and these 2 mechanisms in tandem trigger a moral disengagement process that influences subsequent undermining behaviors. We further theorize that moral identity functions as a boundary condition: high moral identity attenuates whether interpersonal injustice and resource depletion shape moral disengagement and whether moral disengagement translates to subsequent undermining. A field study of bank employees provides empirical support for the mediating mechanisms, and shows that employees who have high moral identity are less likely to respond to interpersonal injustice by morally disengaging and to translate moral disengagement to undermining. (PsycINFO Database Record PMID- 26867103 TI - When ethical leader behavior breaks bad: How ethical leader behavior can turn abusive via ego depletion and moral licensing. AB - The literature to date has predominantly focused on the benefits of ethical leader behaviors for recipients (e.g., employees and teams). Adopting an actor centric perspective, in this study we examined whether exhibiting ethical leader behaviors may come at some cost to leaders. Drawing from ego depletion and moral licensing theories, we explored the potential challenges of ethical leader behavior for actors. Across 2 studies which employed multiwave designs that tracked behaviors over consecutive days, we found that leaders' displays of ethical behavior were positively associated with increases in abusive behavior the following day. This association was mediated by increases in depletion and moral credits owing to their earlier displays of ethical behavior. These results suggest that attention is needed to balance the benefits of ethical leader behaviors for recipients against the challenges that such behaviors pose for actors, which include feelings of mental fatigue and psychological license and ultimately abusive interpersonal behaviors. (PsycINFO Database Record PMID- 26867105 TI - Getting on the same page: The effect of normative feedback interventions on structured interview ratings. AB - This study explores normative feedback as a way to reduce rating errors and increase the reliability and validity of structured interview ratings. Based in control theory and social comparison theory, we propose a model of normative feedback interventions (NFIs) in the context of structured interviews and test our model using data from over 20,000 interviews conducted by more than 100 interviewers over a period of more than 4 years. Results indicate that lenient and severe interviewers reduced discrepancies between their ratings and the overall normative mean rating after receipt of normative feedback, though changes were greater for lenient interviewers. When various waves of feedback were presented in later NFIs, the combined normative mean rating over multiple time periods was more predictive of subsequent rating changes than the normative mean rating from the most recent time period. Mean within-interviewer rating variance, along with interrater agreement and interrater reliability, increased after the initial NFI, but results from later NFIs were more complex and revealed that feedback interventions may lose effectiveness over time. A second study using simulated data indicated that leniency and severity errors did not impact rating validity, but did affect which applicants were hired. We conclude that giving normative feedback to interviewers will aid in minimizing interviewer rating differences and enhance the reliability of structured interview ratings. We suggest that interviewer feedback might be considered as a potential new component of interview structure, though future research is needed before a definitive conclusion can be drawn. (PsycINFO Database Record PMID- 26867106 TI - Power and death: Mortality salience increases power seeking while feeling powerful reduces death anxiety. AB - According to Terror Management Theory, people respond to reminders of mortality by seeking psychological security and bolstering their self-esteem. Because previous research suggests that having power can provide individuals a sense of security and self-worth, we hypothesize that mortality salience leads to an increased motivation to acquire power, especially among men. Study 1 found that men (but not women) who wrote about their death reported more interest in acquiring power. Study 2A and Study 2B demonstrated that when primed with reminders of death, men (but not women) reported behaving more dominantly during the subsequent week, while both men and women reported behaving more prosocially during that week. Thus, mortality salience prompts people to respond in ways that help them manage their death anxiety but in ways consistent with normative gender expectations. Furthermore, Studies 3-5 showed that feeling powerful reduces anxiety when mortality is salient. Specifically, we found that when primed to feel more powerful, both men and women experienced less mortality anxiety. (PsycINFO Database Record PMID- 26867107 TI - How Sodium Chloride Salt Inhibits the Formation of CO2 Gas Hydrates. AB - We present an experimental Raman study on how the addition of sodium chloride to CO2-hydrate-forming systems inhibits the hydrate formation thermodynamically. For this purpose, the molar enthalpy of reaction and the molar entropy of reaction for the reaction of weakly hydrogen-bonded water molecules to strongly hydrogen bonded water molecules are determined for different salinities from the Raman spectrum of the water-stretching vibration. Simultaneously, the influence of the salinity on the solubility of CO2 in the liquid water-rich phase right before the start of hydrate formation is analyzed. The results demonstrate that various mechanisms contribute to the inhibition of gas hydrate formation. For the highest salt concentration of 20 wt % investigated, the temperature of gas hydrate formation is lowered by 12 K. For this concentration the molar enthalpy and entropy of reaction become smaller by 50 and 20%, respectively. Concurrently, the solubility of carbon dioxide is reduced by 70%. These results are compared with data in literature for systems of sodium chloride in water (without carbon dioxide). PMID- 26867108 TI - Pathway-based analyses. AB - BACKGROUND: New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. METHODS: The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. RESULTS: Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. CONCLUSIONS: The work of this group explored several promising approaches to managing high dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation. PMID- 26867109 TI - Effect of nanostructured ceria as support for the iron catalysed hydrogenation of CO2 into hydrocarbons. AB - This paper demonstrates the key role of the property-structure relationship of the support on iron/ceria catalysts on the hydrocarbon selectivity and olefin-to paraffin ratio for the direct hydrogenation of carbon dioxide into hydrocarbons. The effect is directly related to the reducibility of the different nanostructured ceria supports and their interaction with the iron particles. Herein, we demonstrate that the iron-based catalysts can be modified not only by the addition of promoters, commonly reported in the literature, but also by careful control of the morphology of the ceria support. PMID- 26867110 TI - Surface-Enhanced Infrared Spectroscopy and Neutron Reflectivity Studies of Ubiquinone in Hybrid Bilayer Membranes under Potential Control. AB - Surface-enhanced infrared adsorption spectroscopy (SEIRAS) and neutron reflectometry (NR) were employed to characterize ubiquinone (UQ) containing hybrid bilayer membranes. The biomimetic membrane was prepared by fusing phospholipid vesicles on a hydrophobic octadecanethiol monolayer self-assembled on a thin gold film. Using SEIRAS, the assembly of the membrane is monitored in situ. The presence of ubiquinone is verified by the characteristic carbonyl peaks from the quinone ester. A well-ordered distal lipid leaflet results from fusion of vesicles with and without the addition of ubiquinone. With applied potential, the hybrid bilayer membrane in the absence of UQ behaves in the same way as previously reported solid supported phospholipid membranes. When ubiquinone is incorporated in the membrane, electric field induced changes in the distal leaflet are suppressed. Changes in the infrared vibrations of the ubiquinone due to applied potential indicate the head groups are located in both polar and nonpolar environments. The spectroscopic data reveal that the isoprenoid unit of the ubiquinone is likely lying in the midplane of the lipid bilayer while the head has some freedom to move within the hydrophobic core. The SEIRAS experiments show redox behavior of UQ incorporated in a model lipid membrane that are otherwise inaccessible with traditional electrochemistry techniques. PMID- 26867112 TI - The voiced pronunciation of initial phonemes predicts the gender of names. AB - Although it is known that certain names gain popularity within a culture because of historical events, it is unknown how names become associated with different social categories in the first place. We propose that vocal cord vibration during the pronunciation of an initial phoneme plays a critical role in explaining which names are assigned to males versus females. This produces a voiced gendered name effect, whereby voiced phonemes (vibration of the vocal cords) are more associated with male names, and unvoiced phonemes (no vibration of the vocal cords) are more associated with female names. Eleven studies test this association between voiced names and gender (a) using 270 million names (more than 80,000 unique names) given to children over 75 years, (b) names across 2 cultures (the U.S. and India), and (c) hundreds of novel names. The voiced gendered name effect was mediated through how hard or soft names sounded, and moderated by gender stereotype endorsement. Although extensive work has demonstrated morphological and physical cues to gender (e.g., facial, bodily, vocal), this work provides a systematic account of name-based cues to gender. Overall, the current research extends work on sound symbolism to names; the way in which a name sounds can be symbolically related to stereotypes associated with its social category. PMID- 26867111 TI - True grit and genetics: Predicting academic achievement from personality. AB - Grit-perseverance and passion for long-term goals-has been shown to be a significant predictor of academic success, even after controlling for other personality factors. Here, for the first time, we use a U.K.-representative sample and a genetically sensitive design to unpack the etiology of Grit and its prediction of academic achievement in comparison to well-established personality traits. For 4,642 16-year-olds (2,321 twin pairs), we used the Grit-S scale (perseverance of effort and consistency of interest), along with the Big Five personality traits, to predict grades on the General Certificate of Secondary Education (GCSE) exams, which are administered U.K.-wide at the end of compulsory education. Twin analyses of Grit perseverance yielded a heritability estimate of 37% (20% for consistency of interest) and no evidence for shared environmental influence. Personality, primarily conscientiousness, predicts about 6% of the variance in GCSE grades, but Grit adds little to this prediction. Moreover, multivariate twin analyses showed that roughly two-thirds of the GCSE prediction is mediated genetically. Grit perseverance of effort and Big Five conscientiousness are to a large extent the same trait both phenotypically (r = 0.53) and genetically (genetic correlation = 0.86). We conclude that the etiology of Grit is highly similar to other personality traits, not only in showing substantial genetic influence but also in showing no influence of shared environmental factors. Personality significantly predicts academic achievement, but Grit adds little phenotypically or genetically to the prediction of academic achievement beyond traditional personality factors, especially conscientiousness. (PsycINFO Database Record PMID- 26867113 TI - Biomimetic synthesis of highly biocompatible gold nanoparticles with amino acid dithiocarbamate as a precursor for SERS imaging. AB - Amino acid-dithiocarbamate (amino acid-DTC) was developed as both the reductant and ligand stabilizer for biomimetic synthesis of gold nanoparticles (AuNPs), which served as an excellent surface-enhanced Raman scattering (SERS) contrast nanoprobe for cell imaging. Glycine (Gly), glutamic acid (Glu), and histidine (His) with different isoelectric points were chosen as representative amino acid candidates to synthesize corresponding amino acid-DTC compounds through mixing with carbon disulfide (CS2), respectively. The pyrogenic decomposition of amino acid-DTC initiated the reduction synthesis of AuNPs, and the strong coordinating dithiocarbamate group of amino acid-DTC served as a stabilizer that grafted onto the surface of the AuNPs, which rendered the as-prepared nanoparticles a negative surface charge and high colloidal stability. MTT cell viability assay demonstrated that the biomimetic AuNPs possessed neglectful toxicity to the human hepatoma cell, which guaranteed them good biocompatibility for biomedical application. Meanwhile, the biomimetic AuNPs showed a strong SERS effect with an enhancement factor of 9.8 * 10(5) for the sensing of Rhodamine 6G, and two distinct Raman peaks located at 1363 and 1509 cm(-1) could be clearly observed in the cell-imaging experiments. Therefore, biomimetic AuNPs can be explored as an excellent SERS contrast nanoprobe for biomedical imaging, and the amino acid-DTC mediated synthesis of the AuNPs has a great potential in bio-engineering and biomedical imaging applications. PMID- 26867114 TI - An Enzyme Cascade for Selective Modification of Tyrosine Residues in Structurally Diverse Peptides and Proteins. AB - Bioorthogonal chemistry enables a specific moiety in a complex biomolecule to be selectively modified in the presence of many reactive functional groups and other cellular entities. Such selectivity has become indispensable in biology, enabling biomolecules to be derivatized, conjugated, labeled, or immobilized for imaging, biochemical assays, or therapeutic applications. Methyltransferase enzymes (MTase) that accept analogues of the cofactor S-adenosyl methionine have been widely deployed for alkyl-diversification and bioorthogonal labeling. However, MTases typically possess tight substrate specificity. Here we introduce a more flexible methodology for selective derivatization of phenolic moieties in complex biomolecules. Our approach relies on the tandem enzymatic reaction of a fungal tyrosinase and the mammalian catechol-O-methyltransferase (COMT), which can effect the sequential hydroxylation of the phenolic group to give an intermediate catechol moiety that is subsequently O-alkylated. When used in this combination, the alkoxylation is highly selective for tyrosine residues in peptides and proteins, yet remarkably tolerant to changes in the peptide sequence. Tyrosinase COMT are shown to provide highly versatile and regioselective modification of a diverse range of substrates including peptide antitumor agents, hormones, cyclic peptide antibiotics, and model proteins. PMID- 26867115 TI - Hierarchical Carbon with High Nitrogen Doping Level: A Versatile Anode and Cathode Host Material for Long-Life Lithium-Ion and Lithium-Sulfur Batteries. AB - Nitrogen-rich carbon with both a turbostratic microstructure and meso/macroporosity was prepared by hard templating through pyrolysis of a tricyanomethanide-based ionic liquid in the voids of a silica monolith template. This multifunctional carbon not only is a promising anode candidate for long-life lithium-ion batteries but also shows favorable properties as anode and cathode host material owing to a high nitrogen content (>8% after carbonization at 900 degrees C). To demonstrate the latter, the hierarchical carbon was melt infiltrated with sulfur as well as coated by atomic layer deposition (ALD) of anatase TiO2, both of which led to high-quality nanocomposites. TiO2 ALD increased the specific capacity of the carbon while maintaining high Coulombic efficiency and cycle life: the composite exhibited stable performance in lithium half-cells, with excellent recovery of low rate capacities after thousands of cycles at 5C. Lithium-sulfur batteries using the sulfur/carbon composite also showed good cyclability, with reversible capacities of ~700 mA.h.g(-1) at C/5 and without obvious decay over several hundred cycles. The present results demonstrate that nitrogen-rich carbon with an interconnected multimodal pore structure is very versatile and can be used as both active and inactive electrode material in high-performance lithium-based batteries. PMID- 26867116 TI - How in vitro influences in silico utilized for the prediction of in vivo - pilot study of the drug-induced pro-arrhythmic potency prediction. AB - The current drug cardiac safety risk assessment paradigm is about to be changed. The discussed modifications cover clinical as well as pre-clinical sides. As for the latter, the pre-clinical assessment, it is planned to be based on the analysis of the drug-triggered multiple ion currents inhibition. Considering the variability in the in vitro patch clamp studies results, it would be of benefit to assess how these apparatus- and protocol-dependent differences influence the risk prediction and, eventually, the decision making. Four compounds, namely dextromethorphan, ketoconazole, terfenadine, and quinidine were screened for hERG inhibition with an automated patch clamp apparatus (CytoPatch(TM)2). The results were then compared against the literature published data, and after being complemented with information about other current inhibitions and effective therapeutic plasma concentration, utilized for the in silico based safety assessment. Two endpoints were used: (1) the concentration dependent potential to induce early afterdepolarizations in the simulated action potential and (2) the arrhythmia-like disruption in the simulated pseudo-ECG signals. Data analysis results prove that IC50 values, describing the inhibition potential, significantly differ among studies, and the choice of input data can greatly influence the in silico based safety assessment and thus the decision making process. PMID- 26867117 TI - Role of new biomarkers for the diagnosis of nephropathy associated with diabetes type 2. AB - In twenty first century, the incidence of type 2 diabetes mellitus (DMt2) dramatically increases, followed by the number of patients suffering from its complications. Currently, diabetic kidney disease (DKD) is the leading cause of renal replacement therapy. Often, DMt2 is diagnosed after several years of duration, and irreversible organ damage can develop during that period. On the other hand, the early diag- nosis of DKD in the preclinical phase, when glomerular filtration rate (GFR) is still maintained and there are no evident changes in urinalysis, gives the possibility of implementing the nephroprotective treatment that can significantly delay the progression of the disease. However, the diagnostic tests available in clinical practice, i.e. serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria have important limitations. There is a need for new, early and non-invasive biomarkers specific for kidney injury, allowing for differentiation between glomerular and tubular injury, and changing dynamically in response to the degree of kidney damage. Hereby, we review the current knowledge about the novel and emerging biomarkers of kidney injury and their used for the diagnosis of DKD. PMID- 26867119 TI - Rhenium-coated glass beads for intracolonic administration attenuate TNBS-induced colitis in mice: Proof-of-Concept Study. AB - In search for novel effective treatments in inflammatory bowel diseases, a new strategy employing glass beads coated with rhenium nanolayer has been developed and validated in the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colitis. Briefly, mice were randomly divided into 5 experimental groups: control (vehicle alone, Group 1); control treated with rhenium-coated glass beads (Group 2); TNBS (Group 3); TNBS treated with rhenium-coated glass beads (Group 4); and TNBS treated with uncoated glass beads (Group 5). Mice from Group 2, 4 and 5 were treated with respective beads (once daily, 5 beads / animal, i.c.) between D3-D6 post-TNBS/vehicle and evaluation of colonic damage was performed on D7, based on macroscopic scoring and clinical parameters. Severe colonic inflammation developed in post-TNBS mice (Group 3) [P <0.001 vs. control (Group 1) for macroscopic score], which was significantly attenuated by treatment with rhenium-coated glass beads (Group 4) [P <0.01 vs. TNBS (Group 3), for macroscopic score]. Neither rhenium-coated glass beads had any effect in control animals (Group 2), nor uncoated glass beads influenced TNBS-induced colitis (Group 5). In conclusion, a novel and attractive strategy for the treatment of colonic inflammation has been proposed; therapy with rhenium-coated glass beads already proved effective in the mouse model of TNBS-induced colitis, now requires further characterization in clinical conditions. PMID- 26867118 TI - Extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications. AB - INTRODUCTION: Extracellular vesicles (EVs), including circulating microvesicles (MVs) or mi- croparticles (MPs) and exosomes, derived from cells or platelets are present in the peripheral blood and are important elements involved in the activation of the coagulation system, transport of macromolecules and intercellular communication. In patients with vascular complications (including diabetes), the number of EVs is significantly increased during the acute phase of the disease. However, less is known about EVs release in the chronic state of diabetes. OBJECTIVES: To analyse the profile of inflammatory cytokines and angiogenic factors in EVs in diabetic patients with ocular and vascular complications. PATIENTS AND METHODS: The study included patients with diabetes and varying degrees of ocular complications including retinopathy (n = 48) and the control group (n = 13). EV-enriched and EV-depleted fractions were obtained from platelet-poor plasma by means of the centrifugation method (16 000 g, for 90 min). In screening, the profile of cytokines with pro-angiogenic effects was preliminary assessed using the protein microarray technology for controlled diabetic patients - CD, uncontrolled diabetic patients - UD and for the control group. In all patients, concentrations of cytokines: RANTES (Regulated on Activation, Normal T-cell Expressed and secreted) and Ang-2 (angiopoietin-2) were assayed using the ELISA method. Common blood and biochemical tests were performed. RESULTS: In patients with diabetes, analysis of supernatant revealed significantly increased concentrations of basic fibroblast growth factor (bFGF) and soluble receptor for vascular endothelial growth factor 2 (V-EGFR2) when compared to the control group: 49 (10.5-122) vs. 24 (2-72.5) SD (p = 0.03) and 260 (195.5-351) vs. 360 (256-461.5) SD (p = 0.01). In UD patients, concentrations of RANTES, angiostatin, tumor necrosis factor-alpha (TNF), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP1 and TIMP2) were relatively higher in the EV enriched fraction when compared to the EV-depleted fraction. Post hoc analysis revealed significant differences between UC patients and the control group in RANTES (16.73 (14.41-18.93) vs. 14.62 (12.37-15.28) mg/ml; p = 0.0235) and Ang-2 (2.76 (2.23-4.64) ng/ml vs. 1.74 (1.54-1.93); p = 0.0316) concentrations. These analyses did not reveal any significant differences in RANTES and Ang-2 concentrations between CD patients and the control group. CONCLUSIONS: The profiles of cytokines and angiogenic factors in EVs are significantly increased in patients with diabetes. Also, the formation of specific cytokines related to EVs is strongly influenced by disease duration and successful treatment. EVs seem to be the conveyors of upregulated cytokines and angiogenic agents in diabetic patients. PMID- 26867120 TI - Visfatin and TGF-Beta1 in primary biliary cirrhosis and two other common liver diseases. AB - The aim of this study is to investigate plasma concentration of visfatin and transforming growth factor Beta1 (TGF-Beta1) in three groups of patients: primary biliary cirrhosis (PBC), non-alcoholic fatty liver disease (NAFLD) and toxic cirrhosis (TC). We qualified the patients into the study and assigned them to the appropriate group according to clinical examination, laboratory tests and ultrasound imaging technic (US). We showed that plasma concentrations of visfatin in PBC, NAFLD and TC group were respectively 1.41 +/- 1.76 ng/mL, 1.22 +/- 1.08 ng/mL and 0.70 +/- 1.22 ng/mL. Plasma concentration of visfatin was significantly lower in TC group than in others both (p +/- 0.017). The differences of visfatin concentration between NAFLD and TC group were not statistically significant. The values of TGF-Beta1 in PBC, NAFLD and TC group were respectively 21031 +/- 7822 pg/mL, 21588 +/- 12639 pg/mL, and 9678 +/- 4757 pg/mL. The statistical analysis showed that the value of cirrhotic group was significantly (p +/-0.017) lower compared to both others groups. The difference between PBC and NAFLD was insignificant. IN CONCLUSION: Despite the PBC and NAFLD are the diseases of different pathogenesis and origin, plasma concentration of visfatin and TGF-Beta1 were similar in these both groups but significantly lower in TC probably due to decreased activity as well as number of cells producing these cytokines in the cirrhotic liver. PMID- 26867121 TI - Inferior tibiofibular joint (tibiofibular syndesmosis) - own studies and review of the literature. AB - The study was carried out on 50 human lower legs obtained during autopsies. The anatomy of the joint was studied using classical anatomical description methods. Based also on literature we have reviewed the current knowledge on the inferior tibiofibular joint. PMID- 26867122 TI - Volume rendering of the tympanic cavity from micro-CT data. AB - The current study presents volumetric reconstruction of the tympanic cavity obtained from micro-CT scans which pixel size was 18 MUm. Thanks to this, osseous components of the tympanic cavity were shown in high optical resolution, causing that their morphological appearance was clearly demonstrated. Particular attention was paid on imaging the medial wall of the tympanic cavity, because its structures are of clinical importance. In this respect we showed spatial relationship between the promontory, the oval window, the round window and other minute structures like the pyramidal eminence, subiculum and ponticulus. Hence, application of the microcomputed tomography allowed to visualize abnormal osseous formation located within the tympanic cavity, which potentially could interrupt normal movement of the auditory ossicles. PMID- 26867123 TI - Certain remarks on blood supply of normal human uterine corpus - corrosion casting and SEM study. AB - Corrosion casting and scanning electron microscopy are currently best available technique which allows observation of microvascular bed of different anatomical structures and obtaining quasi 3-D pictures, necessary for reconstruction of microvessels. Application of synthetic resins, which fill practically the whole vascular bed enables profound analysis of such obtained specimens. PMID- 26867124 TI - Finite element modeling of human brain response to football helmet impacts. AB - The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions. PMID- 26867125 TI - Antinociceptive Interaction of Tramadol with Gabapentin in Experimental Mononeuropathic Pain. AB - Neuropathic pain is the result of injury to the nervous system, and different animal models have been established to meet the manifestations of neuropathy. The pharmacotherapy for neuropathic pain includes gabapentin and tramadol, but these are only partially effective when given alone. The aim of this study was to assess the antinociceptive interaction between both drugs using the isobolographic analysis and changes of the IL-1beta concentration in a mouse model of neuropathic pain (partial sciatic nerve ligation or PSNL). The i.p. administration of gabapentin (5-100 mg/kg) or tramadol (12.5-100 mg/kg) displayed a dose-dependent antinociception in the hot plate assay of PSNL mice, and effects induced by gabapentin with tramadol were synergistic. Administration of gabapentin or tramadol reversed significantly the increase in the concentration of IL-1beta induced by PSNL after either 7 or 14 days and their combination was significantly more potent in reversing the elevated concentration of IL-1beta. The synergism obtained by the co-administration of gabapentin and tramadol is proposed to result from action on different mechanisms in pain pathways. Gabapentin or tramadol or their combination modulates the expression of pro inflammatory cytokine, IL-1beta, in a model of mice PSNL which could be due to an inhibition of glial function. PMID- 26867127 TI - Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo. AB - OBJECTIVE: Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats. METHODS: For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages. RESULTS: In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and expressed lubricin in the superficial cartilage. CONCLUSION: Cartilage derived from MSCs expressed lubricin protein both in vitro and in vivo. Aggregation promoted lubricin expression of MSCs in vitro and transplantation of aggregates of MSCs regenerated cartilage including the superficial zone in a rat osteochondral defect model. Our results indicate that aggregated MSCs could be clinically relevant for therapeutic approaches to articular cartilage regeneration with an appropriate superficial zone in the future. PMID- 26867126 TI - GDF-15 Is Elevated in Children with Mitochondrial Diseases and Is Induced by Mitochondrial Dysfunction. AB - BACKGROUND: We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF 21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. METHODS: We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. RESULTS: Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3% (81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF 21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. CONCLUSIONS: Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF-21 levels. PMID- 26867130 TI - Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells. AB - Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking). PMID- 26867128 TI - Involvement of the 3' Untranslated Region in Encapsidation of the Hepatitis C Virus. AB - Although information regarding morphogenesis of the hepatitis C virus (HCV) is accumulating, the mechanism(s) by which the HCV genome encapsidated remains unknown. In the present study, in cell cultures producing HCV, the molecular ratios of 3' end- to 5' end-regions of the viral RNA population in the culture medium were markedly higher than those in the cells, and the ratio was highest in the virion-rich fraction. The interaction of the 3' untranslated region (UTR) with Core in vitro was stronger than that of the interaction of other stable RNA structure elements across the HCV genome. A foreign gene flanked by the 3' UTR was encapsidated by supplying both viral NS3-NS5B proteins and Core-NS2 in trans. Mutations within the conserved stem-loops of the 3' UTR were observed to dramatically diminish packaging efficiency, suggesting that the conserved apical motifs of the 3' X region are important for HCV genome packaging. This study provides evidence of selective packaging of the HCV genome into viral particles and identified that the 3' UTR acts as a cis-acting element for encapsidation. PMID- 26867129 TI - Airborne Influenza A Is Detected in the Personal Breathing Zone of Swine Veterinarians. AB - The 2009 H1N1 pandemic emphasized a need to evaluate zoonotic transmission of influenza A in swine production. Airborne influenza A virus has been detected in swine facilities during an outbreak. However, the personal exposure of veterinarians treating infected swine has not been characterized. Two personal bioaerosol samplers, the NIOSH bioaerosol sampler and the personal high-flow inhalable sampler head (PHISH), were placed in the breathing zone of veterinarians treating swine infected with either H1N1 or H3N2 influenza A. A greater number of viral particles were recovered from the NIOSH bioaerosol sampler (2094 RNA copies/m3) compared to the PHISH sampler (545 RNA copies/m3). In addition, the majority of viral particles were detected by the NIOSH bioaerosol sampler in the >4 MUm size fraction. These results suggest that airborne influenza A virus is present in the breathing zone of veterinarians treating swine, and the aerosol route of zoonotic transmission of influenza virus should be further evaluated among agricultural workers. PMID- 26867132 TI - Clinical excellence in physical medicine and rehabilitation: Examples from the published literature. AB - OBJECTIVE: Advancements in medical knowledge and technology are enabling people to live longer with chronic medical conditions, and creating a need for physiatrists to help maintain and restore function. Clinical excellence in physical medicine and rehabilitation (PM&R) is not well documented in the literature. The aim of this paper is to provide examples of clinical excellence in PM&R as they relate to the definition formulated by the Miller-Coulson Academy of Clinical Excellence (MCACE). METHODS AND RESULTS: A review of the literature revealed 1,686 published articles that were evaluated to determine their relevance to the definition of clinical excellence in PM&R. From these articles, exemplary case reports and research studies were identified for each of the domains of excellence. CONCLUSION: The application of the definition of clinical excellence to PM&R is more than just an intellectual exercise, as it can help to establish the model to which physicians and trainees may want to aspire. PMID- 26867133 TI - Motion correction and frequency stabilization for MRS of the human spinal cord. AB - Subject motion is challenging for MRS, because it can falsify results. For spinal cord MRS in particular, subject movement is critical, since even a small movement > 1 mm) can lead to a voxel shift out of the desired measurement region. Therefore, the identification of motion corrupted MRS scans is essential. In this investigation, MR navigators acquired simultaneously with the MRS data are used to identify a displacement of the spinal cord due to subject motion. It is shown that navigators are able to recognize substantial subject motion (>1 mm) without impairing the MRS measurement. In addition, navigators are easy to apply to the measurement, because no additional hardware and just a minor additional user effort are needed. Moreover, no additional scan time is required, because navigators can be applied in the deadtime of the MRS sequence. Furthermore, in this work, retrospective motion correction combined with frequency stabilization is presented by combining navigators with non-water-suppressed (1)H-MRS, resulting in an improved spectral quality of the spinal cord measurements. PMID- 26867134 TI - Practical Approaches for Detecting Selection in Microbial Genomes. AB - Microbial genome evolution is shaped by a variety of selective pressures. Understanding how these processes occur can help to address important problems in microbiology by explaining observed differences in phenotypes, including virulence and resistance to antibiotics. Greater access to whole-genome sequencing provides microbiologists with the opportunity to perform large-scale analyses of selection in novel settings, such as within individual hosts. This tutorial aims to guide researchers through the fundamentals underpinning popular methods for measuring selection in pathogens. These methods are transferable to a wide variety of organisms, and the exercises provided are designed for researchers with any level of programming experience. PMID- 26867131 TI - The Black Yeast Exophiala dermatitidis and Other Selected Opportunistic Human Fungal Pathogens Spread from Dishwashers to Kitchens. AB - We investigated the diversity and distribution of fungi in nine different sites inside 30 residential dishwashers. In total, 503 fungal strains were isolated, which belong to 10 genera and 84 species. Irrespective of the sampled site, 83% of the dishwashers were positive for fungi. The most frequent opportunistic pathogenic species were Exophiala dermatitidis, Candida parapsilosis sensu stricto, Exophiala phaeomuriformis, Fusarium dimerum, and the Saprochaete/Magnusiomyces clade. The black yeast E. dermatitidis was detected in 47% of the dishwashers, primarily at the dishwasher rubber seals, at up to 106 CFU/cm2; the other fungi detected were in the range of 102 to 105 CFU/cm2. The other most heavily contaminated dishwasher sites were side nozzles, doors and drains. Only F. dimerum was isolated from washed dishes, while dishwasher waste water contained E. dermatitidis, Exophiala oligosperma and Sarocladium killiense. Plumbing systems supplying water to household appliances represent the most probable route for contamination of dishwashers, as the fungi that represented the core dishwasher mycobiota were also detected in the tap water. Hot aerosols from dishwashers contained the human opportunistic yeast C. parapsilosis, Rhodotorula mucilaginosa and E. dermatitidis (as well as common air-borne genera such as Aspergillus, Penicillium, Trichoderma and Cladosporium). Comparison of fungal contamination of kitchens without and with dishwashers revealed that virtually all were contaminated with fungi. In both cases, the most contaminated sites were the kitchen drain and the dish drying rack. The most important difference was higher prevalence of black yeasts (E. dermatitidis in particular) in kitchens with dishwashers. In kitchens without dishwashers, C. parapsilosis strongly prevailed with negligible occurrence of E. dermatitidis. F. dimerum was isolated only from kitchens with dishwashers, while Saprochaete/Magnusiomyces isolates were only found within dishwashers. We conclude that dishwashers represent a reservoir of enriched opportunistic pathogenic species that can spread from the dishwasher into the indoor biome. PMID- 26867135 TI - IL-17a and IL-22 Induce Expression of Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell Defense against Helicobacter pylori. AB - Helicobacter pylori colonization of the human stomach can lead to adverse clinical outcomes including gastritis, peptic ulcers, or gastric cancer. Current data suggest that in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization. Specifically, CD4+ T cell responses impact the pathology elicited in response to H. pylori. Because gastritis is believed to be the initiating host response to more detrimental pathological outcomes, there has been a significant interest in pro inflammatory T cell cytokines, including the cytokines produced by T helper 17 cells. Th17 cells produce IL-17A, IL-17F, IL-21 and IL-22. While these cytokines have been linked to inflammation, IL-17A and IL-22 are also associated with anti microbial responses and control of bacterial colonization. The goal of this research was to determine the role of IL-22 in activation of antimicrobial responses in models of H. pylori infection using human gastric epithelial cell lines and the mouse model of H. pylori infection. Our data indicate that IL-17A and IL-22 work synergistically to induce antimicrobials and chemokines such as IL 8, components of calprotectin (CP), lipocalin (LCN) and some beta-defensins in both human and primary mouse gastric epithelial cells (GEC) and gastroids. Moreover, IL-22 and IL-17A-activated GECs were capable of inhibiting growth of H. pylori in vitro. While antimicrobials were activated by IL-17A and IL-22 in vitro, using a mouse model of H. pylori infection, the data herein indicate that IL-22 deficiency alone does not render mice more susceptible to infection, change their antimicrobial gene transcription, or significantly change their inflammatory response. PMID- 26867137 TI - Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel Lymph Node Mapping After Periareolar Nuclide Injection. AB - BACKGROUND: To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients. METHODS AND FINDINGS: 767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5). CONCLUSIONS: Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed. PMID- 26867138 TI - Body Mass Index and Decline of Cognitive Function. AB - BACKGROUND: The association between body mass index (BMI) and cognitive function is a public health issue. This study investigated the relationship between obesity and cognitive impairment which was assessed by the Korean version of the Mini-mental state examination (K-MMSE) among mid- and old-aged people in South Korea. METHODS: A cohort of 5,125 adults, age 45 or older with normal cognitive function (K-MMSE>=24) at baseline (2006), was derived from the Korean Longitudinal Study of Aging (KLoSA) 2006~2012. The association between baseline BMI and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed baseline BMI and change of cognitive function over the 6-year follow-up using multiple linear regressions. RESULTS: During the follow-up, 358 cases of severe cognitive impairment were identified. Those with baseline BMI>=25 kg/m2 than normal-weight (18.5<=BMI<23 kg/m2) were marginally less likely to experience the development of severe cognitive impairment (adjusted odds ratio [aOR] = 0.73, 95% CI = 0.52 to 1.03; Ptrend = 0.03). This relationship was stronger among female (aOR = 0.63, 95% CI = 0.40 to 1.00; Ptrend = 0.01) and participants with low-normal K-MMSE score (MMSE: 24-26) at baseline (aOR = 0.59, 95% CI = 0.35 to 0.98; Ptrend<0.01). In addition, a slower decline of cognitive function was observed in obese individuals than those with normal weight, especially among women and those with low-normal K-MMSE score at baseline. CONCLUSION: In this nationally representative study, we found that obesity was associated with lower risk of cognitive decline among mid- and old age population. PMID- 26867136 TI - Atazanavir exposure in utero and neurodevelopment in infants: a comparative safety study. AB - OBJECTIVE: To evaluate the safety of in-utero exposure to atazanavir and neurodevelopment in perinatally HIV-exposed but uninfected (PHEU) infants. DESIGN: Prospective cohort study of mother-PHEU infant pairs in the Surveillance Monitoring for ART Toxicities protocol of the Pediatric HIV/AIDS Cohort Study. METHODS: Pregnant women living with HIV who initiated an antiretroviral regimen during pregnancy were followed from the date of antiretroviral initiation. Women were classified according to whether the antiretroviral regimen contained atazanavir and the trimester of antiretroviral initiation. Neurodevelopment at 9 15 months was evaluated using the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III). We estimated mean differences for the five Bayley-III domains for atazanavir-containing regimens versus all other regimens. Models included baseline covariates and adjustment for failure to complete the Bayley III using inverse probability weighting. RESULTS: PHEU infants were exposed in utero to atazanavir-containing (n = 167) and nonatazanavir-containing (n = 750) antiretroviral regimens. The adjusted mean differences (95% confidence interval) in Bayley-III domain scores for initiating an atazanavir-containing regimen in the first trimester were: cognitive, -1.5 (-6.2, 3.2); language, -3.3 (-7.6, 1.0); motor, -2.9 (-7.7, 1.9); social-emotional, 0.1 (-6.2, 6.4); and adaptive behavior, -0.1 (-4.3, 4.0). The mean differences for the second or third trimester were: cognitive, 0.4 (-3.2, 4.0); language, -3.4 (-6.2, -0.5); motor, 0.3 (-2.9, 3.4); social-emotional, -5.9 (-9.4, -2.3); and adaptive behavior, -2.5 (-5.9, 0.8). CONCLUSION: In-utero exposure to atazanavir-containing regimens compared with non-atazanavir-containing regimens may adversely affect language and social-emotional development in PHEU infants during the first year of life, but the absolute difference is small. PMID- 26867139 TI - Internet-Delivered Cognitive Behavioral Therapy to Treat Insomnia: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Insomnia is of major public health importance. While cognitive behavioral therapy is beneficial, in-person treatment is often unavailable. We assessed the effectiveness of internet-delivered cognitive behavioral therapy for insomnia. OBJECTIVES: The primary objectives were to determine whether online cognitive behavioral therapy for insomnia could improve sleep efficiency and reduce the severity of insomnia in adults. Secondary outcomes included sleep quality, total sleep time, time in bed, sleep onset latency, wake time after sleep onset, and number of nocturnal awakenings. DATA SOURCES: We searched PubMed/MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo, Cochrane Library, Embase, and the Web of Science for randomized trials. METHODS: Studies were eligible if they were randomized controlled trials in adults that reported application of cognitive behavioral therapy for insomnia via internet delivery. Mean differences in improvement in sleep measures were calculated using the Hartung-Knapp-Sidik-Jonkman method for random effects meta analysis. RESULTS: We found 15 trials, all utilizing a pretest-posttest randomized control group design. Sleep efficiency was 72% at baseline and improved by 7.2% (95% CI: 5.1%, 9.3%; p<0.001) with internet-delivered cognitive behavioral therapy versus control. Internet-delivered cognitive behavioral therapy resulted in a decrease in the insomnia severity index by 4.3 points (95% CI: -7.1, -1.5; p = 0.017) compared to control. Total sleep time averaged 5.7 hours at baseline and increased by 20 minutes with internet-delivered therapy versus control (95% CI: 9, 31; p = 0.004). The severity of depression decreased by 2.3 points (95% CI: -2.9, -1.7; p = 0.013) in individuals who received internet-delivered cognitive behavioral therapy compared to control. Improvements in sleep efficiency, the insomnia severity index and depression scores with internet-delivered cognitive behavioral therapy were maintained from 4 to 48 weeks after post-treatment assessment. There were no statistically significant differences between sleep efficiency, total sleep time, and insomnia severity index for internet-delivered versus in-person therapy with a trained therapist. CONCLUSION: In conclusion, internet-delivered cognitive behavioral therapy is effective in improving sleep in adults with insomnia. Efforts should be made to educate the public and expand access to this therapy. Registration Number, Prospero: CRD42015017622. PMID- 26867140 TI - Simultaneous cross-linking and p-doping of a polymeric semiconductor film by immersion into a phosphomolybdic acid solution for use in organic solar cells. AB - Poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3' benzothiadiazole)] (PCDTBT) is shown to be simultaneously cross-linked and p doped when immersed into a phosphomolybdic acid solution, yielding conductive films with low solubility that can withstand the solution processing of subsequent photoactive layers. Such a modified PCDTBT film serves to improve hole collection and limit carrier recombination in organic solar cells. PMID- 26867141 TI - Endurance Exercise Improves Molecular Pathways of Aerobic Metabolism in Patients With Myositis. AB - OBJECTIVE: Endurance exercise demonstrates beneficial effects in polymyositis/dermatomyositis (PM/DM); however, the molecular effects of exercise on skeletal muscle are incompletely understood. We undertook this controlled pilot study to investigate the effects of a 12-week endurance exercise training program on the molecular profile of skeletal muscle in patients with established PM/DM compared to a nonexercised control group of patients with established PM/DM. METHODS: Fifteen patients (7 in the exercise group and 8 in the control group) with paired baseline and 12-week follow-up muscle biopsy samples were included. Messenger RNA expression profiling, mass spectrometry-based quantitative proteomics, and immunohistochemical analyses were performed on muscle biopsy samples to determine molecular adaptations associated with changes in clinical measurements induced by endurance exercise. RESULTS: Compared to the control group, the exercise group improved in minutes of cycling time (P < 0.01) and Vo2 max (P < 0.05). The exercise group also had reduced disease activity (P < 0.05) and reduced lactate levels at exhaustion (P < 0.05). Genes related to capillary growth, mitochondrial biogenesis, protein synthesis, cytoskeletal remodeling, and muscle hypertrophy were up-regulated in the exercise group, while genes related to inflammation/immune response and endoplasmic reticulum stress were down-regulated. Mitochondrial pathways including the oxidative phosphorylation metabolic pathway were most affected by the endurance exercise, as demonstrated by proteomics analysis. The exercise group also showed a higher number of capillaries per mm(2) in follow-up biopsy samples (P < 0.05). CONCLUSION: Our data indicate that endurance exercise in patients with established PM and DM may activate an aerobic phenotype and promote muscle growth and simultaneously suppress the inflammatory response in these patients' muscles, as supported by a combination of data on gene expression, proteomics, and capillary density in repeated muscle biopsies. PMID- 26867142 TI - The Organization of Repetitive DNA in the Genomes of Amazonian Lizard Species in the Family Teiidae. AB - Repetitive DNA is the largest fraction of the eukaryote genome and comprises tandem and dispersed sequences. It presents variations in relation to its composition, number of copies, distribution, dynamics, and genome organization, and participates in the evolutionary diversification of different vertebrate species. Repetitive sequences are usually located in the heterochromatin of centromeric and telomeric regions of chromosomes, contributing to chromosomal structures. Therefore, the aim of this study was to physically map repetitive DNA sequences (5S rDNA, telomeric sequences, tropomyosin gene 1, and retroelements Rex1 and SINE) of mitotic chromosomes of Amazonian species of teiids (Ameiva ameiva, Cnemidophorus sp. 1, Kentropyx calcarata, Kentropyx pelviceps, and Tupinambis teguixin) to understand their genome organization and karyotype evolution. The mapping of repetitive sequences revealed a distinct pattern in Cnemidophorus sp. 1, whereas the other species showed all sequences interspersed in the heterochromatic region. Physical mapping of the tropomyosin 1 gene was performed for the first time in lizards and showed that in addition to being functional, this gene has a structural function similar to the mapped repetitive elements as it is located preferentially in centromeric regions and termini of chromosomes. PMID- 26867143 TI - Validity of a selection of pregnancy complications in the Medical Birth Registry of Norway. AB - INTRODUCTION: The validity of information on pregnancy complications in the Medical Birth Registry of Norway (MBRN) is insufficiently studied. The objective was to examine the validity of information on gestational age, birthweight, medically initiated delivery, and gestational hypertension in the MBRN. MATERIAL AND METHODS: We randomly sampled MBRN records among women who participated in the population-based HUNT Study in Nord-Trondelag county and who gave birth during 1967-2012. We estimated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value of information in the MBRN, using hospital records as the reference standard. RESULTS: Hospital records were available for 786 out of 797 sampled MBRN records. The PPVs of preterm (<37 weeks of gestation) and early preterm birth (<34 weeks of gestation) were approximately 90%, and the PPVs of low (<2500 g) and high (>4500 g) birthweight were 100%. For medically initiated delivery, the PPV was 28% during 1967-85, but 80% during 1986-2012 and higher among preterm (76%) than among term (51%) births. For gestational hypertension, the PPV was 68%, but 88% of women labeled with gestational hypertension in the MBRN had evidence of gestational hypertension or preeclampsia in hospital records. CONCLUSIONS: The validity of information on gestational age and birthweight in the MBRN was very good. For medically initiated delivery, the validity was poor before 1985 and satisfactory thereafter. For gestational hypertension, lack of information in hospital records made the evaluation difficult, but our results suggest that most women labeled with gestational hypertension in the MBRN did have a hypertensive disorder of pregnancy. PMID- 26867144 TI - Association of Anticentromere Antibodies With More Severe Exocrine Glandular Dysfunction in Sjogren's Syndrome: Analysis of the Sjogren's International Collaborative Clinical Alliance Cohort. AB - OBJECTIVE: Anticentromere antibodies (ACAs) define a subset of primary Sjogren's syndrome (SS) with a unique phenotype, including features of limited cutaneous systemic sclerosis and a lower frequency of anti-SSA/SSB antibodies. We sought to determine whether ACAs are associated with more severe exocrine glandular dysfunction in a large cohort of primary SS subjects. METHODS: We performed a cross-sectional analysis of 1,361 subjects with primary SS from the Sjogren's International Collaborative Clinical Alliance Registry, stratified by the presence or absence of ACAs. ACAs were assayed by immunofluorescence staining on HEp-2 cells. RESULTS: ACAs were present in 82 of the 1,361 SS subjects (6%) and were associated with older age, female sex, and lower frequencies of anti SSA/SSB, rheumatoid factor, and hyperglobulinemia. Among ACA-positive versus ACA negative subjects, there was a higher frequency of a focus score >=2 (71% versus 53%; P = 0.002), a higher median focus score (2.8 versus 2.5; P = 0.0440), and greater exocrine gland dysfunction: Schirmer's test value: median 4 versus 5 mm/5 minutes; P = 0.0003, and unstimulated whole saliva (UWS) flow rate: median 0.08 versus 0.37 ml/5 minutes; P < 0.0001. ACA-positive subjects had an increased risk of UWS <0.1 ml/minute (odds ratio [OR] 12.24 [95% confidence interval (95% CI) 4.91-41.02]) and Schirmer's test value <5 mm/5 minutes (OR 2.52 [95% CI 1.50 4.36]) after correcting for age, sex, anti-SSA/SSB, and focus score. Labial gland fibrosis was not different between the 2 groups. CONCLUSION: In a large international registry of SS, ACA had an independent association with more severe exocrine glandular dysfunction. This dysfunction was associated with more pronounced labial salivary glandular inflammation but not fibrosis. PMID- 26867145 TI - Why Was Silcrete Heat-Treated in the Middle Stone Age? An Early Transformative Technology in the Context of Raw Material Use at Mertenhof Rock Shelter, South Africa. AB - People heat treated silcrete during the Middle Stone Age (MSA) in southern Africa but the spatial and temporal variability of this practice remains poorly documented. This paucity of data in turn makes it difficult to interrogate the motive factors underlying the application of this technique. In this paper we present data on heat treatment of silcrete through the Howiesons Poort and post Howiesons Poort of the rock shelter site Mertenhof, located in the Western Cape of South Africa. In contrast to other sites where heat treatment has been documented, distance to rock source at Mertenhof can be reasonably well estimated, and the site is known to contain high proportions of a diversity of fine grained rocks including silcrete, hornfels and chert at various points through the sequence. Our results suggest the prevalence of heat treatment is variable through the sequence but that it is largely unaffected by the relative abundance of silcrete prevalence. Instead there is a strong inverse correlation between frequency of heat treatment in silcrete and prevalence of chert in the assemblage, and a generally positive correlation with the proportion of locally available rock. While it is difficult to separate individual factors we suggest that, at Mertenhof at least, heat treatment may have been used to improve the fracture properties of silcrete at times when other finer grained rocks were less readily available. As such, heat treatment appears to have been a component of the MSA behavioural repertoire that was flexibly deployed in ways sensitive to other elements of technological organisation. PMID- 26867146 TI - HIV-Related Risk Behaviors Among Male High School Students Who Had Sexual Contact with Males - 17 Large Urban School Districts, United States, 2009-2013. AB - Young persons aged 13-24 years accounted for an estimated 22% of all new diagnoses of human immunodeficiency virus (HIV) infection in the United States in 2014. Most new HIV diagnoses among youths occur among males who have sex with males (MSM). Among all MSM, young black MSM accounted for the largest number of new HIV diagnoses in 2014 (1). To determine whether the prevalence of HIV-related risk behaviors among black male high school students who had sexual contact with males differed from the prevalence among white and Hispanic male students who had sexual contact with males, potentially contributing to the racial/ethnic disparities in new HIV diagnoses, CDC analyzed data from Youth Risk Behavior Surveys conducted by 17 large urban school districts during 2009-2013. Although other studies have examined HIV-related risk behaviors among MSM (2,3), less is known about MSM aged <18 years. Black male students who had sexual contact with males had a lower or similar prevalence of most HIV-related risk behaviors than did white and Hispanic male students who had sexual contact with males. These findings highlight the need to increase access to effective HIV prevention strategies for all young MSM. PMID- 26867149 TI - Recommendations in the American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis Related to the Use of Biologic Agents in Patients With a History of Cancer Need Reconsideration: Comment on the Article by Singh et al. PMID- 26867147 TI - Tumor Necrosis Factor alpha Regulates Endothelial Progenitor Cell Migration via CADM1 and NF-kB. AB - Shortly after the discovery of endothelial progenitor cells (EPCs) in 1997, many clinical trials were conducted using EPCs as a cellular based therapy with the goal of restoring damaged organ function by inducing growth of new blood vessels (angiogenesis). Results were disappointing, largely because the cellular and molecular mechanisms of EPC-induced angiogenesis were not clearly understood. Following injection, EPCs must migrate to the target tissue and engraft prior to induction of angiogenesis. In this study EPC migration was investigated in response to tumor necrosis factor alpha (TNFalpha), a pro-inflammatory cytokine, to test the hypothesis that organ damage observed in ischemic diseases induces an inflammatory signal that is important for EPC homing. In this study, EPC migration and incorporation were modeled in vitro using a coculture assay where TNFalpha treated EPCs were tracked while migrating toward vessel-like structures. It was found that TNFalpha treatment of EPCs increased migration and incorporation into vessel-like structures. Using a combination of genomic and proteomic approaches, NF-kB mediated upregulation of CADM1 was identified as a mechanism of TNFalpha induced migration. Inhibition of NF-kB or CADM1 significantly decreased migration of EPCs in vitro suggesting a role for TNFalpha signaling in EPC homing during tissue repair. Stem Cells 2016;34:1922-1933. PMID- 26867148 TI - Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage. AB - Deciphering the extracellular signals that regulate SMC differentiation from stem cells is vital to further our understanding of the pathogenesis of vascular disease and for development of cell-based therapies and tissue engineering. Hyaluronan (HA) has emerged as an important component of the stem cell niche, however its role during stem cell differentiation is a complicated and inadequately defined process. This study aimed to investigate the role of HA in embryonic stem cell (ESC) differentiation toward a SMC lineage. ESCs were seeded on collagen-IV in differentiation medium to generate ESC-derived SMCs (esSMCs). Differentiation coincided with increased HA synthase (HAS) 2 expression, accumulation of extracellular HA and its assembly into pericellular matrices. Inhibition of HA synthesis by 4-methylumbelliferone (4MU), removal of the HA coat by hyaluronidase (HYAL) or HAS2 knockdown led to abrogation of SMC gene expression. HA activates ERK1/2 and suppresses EGFR signaling pathways via its principle receptor, CD44. EGFR inactivation coincided with increased binding to CD44, which was further augmented by addition of high molecular weight (HMW)-HA either exogenously or via HAS2 overexpression through adenoviral gene transfer. HMW-HA-stimulated esSMCs displayed a functional role in vascular tissue engineering ex vivo, vasculogenesis in a matrigel plug model and SMC accumulation in neointimal lesions of vein grafts in mice. These findings demonstrate that HAS2-induced HA synthesis and organization drives ESC-SMC differentiation. Thus, remodeling of the HA microenvironment is a critical step in directing stem cell differentiation toward a vascular lineage, highlighting HA as a potential target for treatment of vascular diseases. Stem Cells 2016;34:1225-1238. PMID- 26867151 TI - Novel Candidate Biomarkers of Chemoradiosensitivity in Esophageal Squamous Cell Carcinoma: A Systematic Review. AB - There is no doubt that, along with surgery, chemoradiotherapy is an important treatment for esophageal squamous cell carcinoma (ESCC). Patients who respond well to chemoradiotherapy obtain great benefits toward overcoming their cancer, and so a more favorable prognosis. On the other hand, patients who do not respond well have wasted valuable time and experienced severe toxicity and seriously diminished quality of life, only to have their cancer recur with an unfavorable prognosis. For this reason, a reliable biomarker of chemoradiosensitivity in ESCC has long been sought. In this review, we will enumerate recently reported candidate biomarkers of chemoradiosensitivity in ESCC that have the potential for future clinical application. PMID- 26867152 TI - Congenital omphalocele and cleft palate in two fetuses. PMID- 26867150 TI - A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions. AB - Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies. PMID- 26867153 TI - In memoriam--A salute to Dr. Carlos F. Salinas and Dr. Robert Goltz. PMID- 26867154 TI - Green organocatalytic alpha-hydroxylation of ketones. AB - An efficient and green method for the alpha-hydroxylation of substituted ketones has been developed. This method includes the in situ conversion of various ketones into the corresponding silyl enol ethers and their oxidation to the corresponding alpha-hydroxy ketones. Two protocols have been established leading either to protected alpha-hydroxy carbonyls or free alpha-hydroxy ketones. Both procedures are easy to follow and lead to good to high yields for a variety of ketones. PMID- 26867155 TI - The shifted Wald distribution for response time data analysis. AB - We propose and demonstrate the shifted Wald (SW) distribution as both a useful measurement tool and intraindividual process model for psychological response time (RT) data. Furthermore, we develop a methodology and fitting approach that readers can easily access. As a measurement tool, the SW provides a detailed quantification of the RT data that is more sophisticated than mean and SD comparisons. As an intraindividual process model, the SW provides a cognitive model for the response process in terms of signal accumulation and the threshold needed to respond. The details and importance of both of these features are developed, and we show how the approach can be easily generalized to a variety of experimental domains. The versatility and usefulness of the approach is demonstrated on 3 published data sets, each with a different canonical mode of responding: manual, vocal, and oculomotor modes. In addition, model-fitting code is included with the article. (PsycINFO Database Record PMID- 26867156 TI - Dynamical correlation: A new method for quantifying synchrony with multivariate intensive longitudinal data. AB - In this article, we introduce dynamical correlation, a new method for quantifying synchrony between 2 variables with intensive longitudinal data. Dynamical correlation is a functional data analysis technique developed to measure the similarity of 2 curves. It has advantages over existing methods for studying synchrony, such as multilevel modeling. In particular, it is a nonparametric approach that does not require a prespecified functional form, and it places no assumption on homogeneity of the sample. Dynamical correlation can be easily estimated with irregularly spaced observations and tested to draw population level inferences. We illustrate this flexible statistical technique with a simulation example and empirical data from an experiment examining interpersonal physiological synchrony between romantic partners. We discuss the advantages and limitations of the method, and how it can be extended and applied in psychological research. We also provide a set of R code for other researchers to estimate and test for dynamical correlation. (PsycINFO Database Record PMID- 26867157 TI - Panitumumab added to docetaxel, cisplatin and fluoropyrimidine in oesophagogastric cancer: ATTAX3 phase II trial. AB - BACKGROUND: This randomised phase II study evaluated the efficacy and safety of panitumumab added to docetaxel-based chemotherapy in advanced oesophagogastric cancer. METHODS: Patients with metastatic or locally recurrent cancer of the oesophagus, oesophagogastric junction or stomach received docetaxel and a fluoropyrimidine with or without panitumumab for 8 cycles or until progression. The primary end point was response rate (RECIST1.1). We planned to enrol 100 patients, with 50% expected response rate for combination therapy. RESULTS: A total of 77 patients were enrolled. A safety alert from the REAL3 trial prompted a review of data that found no evidence of adverse outcomes associated with panitumumab but questionable efficacy, and new enrolment was ceased. Enrolled patients were treated according to protocol. Response rates were 49% (95% CI 34 64%) in the chemotherapy arm and 58% (95% CI 42-72%) in the combination arm. Common grade 3 and 4 toxicities included infection, anorexia, vomiting, diarrhoea and fatigue. At 23.7 months of median follow-up, median progression-free survival was 6.9 months vs 6.0 months and median overall survival was 11.7 months vs 10.0 months in the chemotherapy arm and the combination arm, respectively. CONCLUSIONS: Adding panitumumab to docetaxel-based chemotherapy for advanced oesophagogastric cancer did not improve efficacy and increased toxicities. PMID- 26867158 TI - Arpin downregulation in breast cancer is associated with poor prognosis. AB - BACKGROUND: The Arp2/3 complex is required for cell migration and invasion. The Arp2/3 complex and its activators, such as the WAVE complex, are deregulated in diverse cancers. Here we investigate the expression of Arpin, the Arp2/3 inhibitory protein that antagonises the WAVE complex. METHODS: We used qRT-PCR and reverse phase protein arrays in a patient cohort with known clinical parameters and outcome, immunofluorescence in breast biopsy cryosections and breast cancer cell lines. RESULTS: Arpin was downregulated at the mRNA and protein levels in mammary carcinoma cells. Arpin mRNA downregulation was associated with poor metastasis-free survival (MFS) on univariate analysis (P=0.022). High expression of the NCKAP1 gene that encodes a WAVE complex subunit was also associated with poor MFS on univariate analysis (P=0.0037) and was mutually exclusive with Arpin low. Arpin low or NCKAP1 high was an independent prognosis factor on multivariate analysis (P=0.0012) and was strongly associated with poor MFS (P=0.000064). CONCLUSIONS: Loss of the Arp2/3 inhibitory protein Arpin produces a similar poor outcome in breast cancer as high expression of the NCKAP1 subunit of the Arp2/3 activatory WAVE complex. PMID- 26867159 TI - Cancer fear and fatalism among ethnic minority women in the United Kingdom. AB - BACKGROUND: Cancer fear and fatalism are believed to be higher in ethnic minorities and may contribute to lower engagement with cancer prevention and early detection. We explored the levels of cancer fear and fatalism in six ethnic groups in the United Kingdom and examined the contribution of acculturation and general fatalism. METHODS: A cross-sectional survey of 720 White British, Caribbean, African, Indian, Pakistani, and Bangladeshi women (120 of each) was conducted. Three items assessed cancer fear and two cancer fatalism. Acculturation was assessed using (self-reported) migration status, ability to speak English, and understanding of health leaflets; general fatalism with a standard measure. RESULTS: Relative to White British women, African and Indian women were more fearful of cancer, Bangladeshi women less fearful, and Pakistani and Caribbean women were similar to White British women. Cancer fatalism was higher in all the ethnic minority groups compared with White British women. Less acculturated women were less likely to worry (ORs 0.21-0.45, all P<0.05) or feel particularly afraid (ORs 0.11-0.31, all P<0.05) but more likely to feel uncomfortable about cancer (ORs 1.97-3.03, all P<0.05). Lower acculturation (ORs 4.30-17.27, P<0.05) and general fatalism (OR 2.29, P<0.05) were associated with the belief that cancer is predetermined. CONCLUSIONS: In general, cancer fear and fatalism are more prevalent among ethnic minority than White British women and even more so in less acculturated ethnic minorities. This may affect their participation in cancer prevention and early detection. PMID- 26867160 TI - Long-term use of lithium and risk of colorectal adenocarcinoma: a nationwide case control study. AB - BACKGROUND: Lithium accumulates in the colon and inhibits the enzyme GSK-3beta that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS: We used the Danish Cancer Registry to identify all patients diagnosed with incident colorectal adenocarcinoma during 2000-2012 (n=36 248). Using a matched case control approach, we estimated the association between long-term use (?5 years) of lithium and risk of colorectal adenocarcinoma using conditional logistic regression. RESULTS: Long-term use of lithium was similar among cases (0.22%) and controls (0.20%), yielding an odds ratio of 1.13 (95% confidence interval (CI), 0.89-1.43) for colorectal adenocarcinoma. Dose-response, subgroup and other subanalyses returned neutral associations. However, ORs differed for colorectal subsites (proximal colon: 1.01 (95% CI, 0.66-1.55; distal colon: 1.52 (95% CI, 1.05-2.20); and rectum: 0.80 (95% CI, 0.50-1.30). CONCLUSIONS: Lithium use was not associated with an overall increased risk of colorectal adenocarcinoma. The variation by subsite warrants further investigation. PMID- 26867161 TI - Do no harm: no psychological harm from colorectal cancer screening. AB - BACKGROUND: Participation in cancer screening programmes might cause worries in the population outweighting the benefits of reduced mortality. The present study aimed to investigate possible psychological harm of participation in a colorectal cancer (CRC) screening pilot in Norway. METHODS: In a prospective, randomised trial participants (aged 50-74 years) were invited to either flexible sigmoidoscopy (FS) screening, faecal immunochemical test (FIT), or no screening (the control group; 1 : 1: 1). Three thousand two hundred and thirteen screening participants (42% of screened individuals) completed the Hospital Anxiety and Depression Scale questionnaire as well as the SF-12-a health-related quality of life (HRQOL) questionnaire when invited to screening and when receiving the screening result. A control group was invited to complete the questionnaires only. Two thousand six hundred and eighteen control participants (35% of invited individuals) completed the questionnaire. RESULTS: A positive screening result did not increase participants' level of anxiety or depression, or decrease participants' level of HRQOL. Participants who received a negative result reported decreased anxiety and improvement on some HRQOL dimensions. However, no change was considered to be of clinical relevance. CONCLUSION: The current study showed no clinically relevant psychological harm of receiving a positive CRC screening result or of participating in FS or FIT screening, in a Norwegian population. PMID- 26867164 TI - Addressing substance misuse in adolescents: a review of the literature on the screening, brief intervention, and referral to treatment model. AB - PURPOSE OF REVIEW: Adolescent substance use is a major public health concern in the United States. Pediatricians are in a unique position via the medical home to address this issue. Screening, brief intervention, and referral to treatment (SBIRT) is a comprehensive approach that aims to prevent, identify, and reduce substance use. SBIRT has been heavily studied in adults, but research with adolescents is still ongoing. This review examines the SBIRT model and highlights recent applicable research. RECENT FINDINGS: This research indicates that alcohol and drug use has a negative impact on the developing brain. In 2011, the American Academy of Pediatrics (AAP) released a policy statement recommending the use of SBIRT. An adolescent SBIRT algorithm can be used clinically. Recent studies focus on individual components of SBIRT; however, there have been no studies that examine all three components together in adolescents. Nevertheless, research indicates that SBIRT is an important tool to assess and intervene regarding adolescent substance use. SUMMARY: SBIRT is recommended by the AAP as a way to address adolescent substance use. Pediatricians should be screening adolescents for substance use at every well exam, and acute care visits when possible, with a validated tool. Although more research is needed, SBIRT is an effective method to address adolescent substance use. PMID- 26867163 TI - Human papillomavirus vaccination induces neutralising antibodies in oral mucosal fluids. AB - BACKGROUND: Mucosal human papillomaviruses (HPV) are a major cause of cancers and papillomas of the anogenital and oropharyngeal tract. HPV-vaccination elicits neutralising antibodies in sera and cervicovaginal secretions and protects uninfected individuals from persistent anogenital infection and associated diseases caused by the vaccine-targeted HPV types. Whether immunisation can prevent oropharyngeal infection and diseases and whether neutralising antibodies represent the correlate of protection, is still unclear. METHODS: We determined IgG and neutralising antibodies against low-risk HPV6 and high-risk HPV16/18 in sera and oral fluids from healthy females (n=20) before and after quadrivalent HPV-vaccination and compared the results with non-vaccinated controls. RESULTS: HPV-vaccination induced type-specific antibodies in sera and oral fluids of the vaccinees. Importantly, the antibodies in oral fluids were capable of neutralising HPV pseudovirions in vitro, indicating protection from infection. The increased neutralising antibody levels against HPV16/18 in sera and oral fluids post-vaccination correlated significantly within an individual. CONCLUSIONS: We provide experimental proof that HPV-vaccination elicits neutralising antibodies to the vaccine-targeted types in oral fluids. Hence, immunisation may confer direct protection against type-specific HPV infection and associated diseases of the oropharyngeal tract. Measurement of antibodies in oral fluids represents a suitable tool to assess vaccine-induced protection within the mucosal milieu of the orophayrynx. PMID- 26867162 TI - Chetomin, targeting HIF-1alpha/p300 complex, exhibits antitumour activity in multiple myeloma. AB - BACKGROUND: Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. The constitutive expression of HIF-1alpha in MM suggests that inhibition of HIF 1alpha-mediated transcription represents an interesting target in MM. METHODS: As p300 is a crucial co-activator of hypoxia-inducible transcription, disrupting the complex HIF-1alpha/p300 to target HIF activity appears to be an attractive strategy. RESULTS: We reported that chetomin, an inhibitor of HIF-1alpha/p300 interaction, exhibits antitumour activity in human myeloma cell lines and primary MM cells from patients. CONCLUSIONS: Our data suggest that chetomin may be of clinical value in MM and especially for patients characterised by a high EP300/HIF-1alpha expression and a poor prognosis. PMID- 26867165 TI - Consumer products as sources of chemical exposures to children: case study of triclosan. AB - PURPOSE OF REVIEW: Consumer products are often overlooked as sources of children's exposures to toxic chemicals. Various regulatory bodies have developed lists of chemicals of concern that can be found in products contacted by children. However, this information has not been summarized for health practitioners. This review organizes such chemicals and products into four categories, with the antibacterial agent triclosan used to illustrate the potential risks to children from a common ingredient in consumer products. RECENT FINDINGS: Biomonitoring, house dust, indoor air, and product testing document children's exposures to a wide variety of chemicals. An increasing number of epidemiology studies have shown associations between these exposures and health effects in children. Triclosan is an example of a chemical contained in high contact products (e.g., soaps, lotions, and toothpaste) not necessarily designed for children. Triclosan exposure in children has been associated with increased responsiveness to airway allergens, with it also capable of endocrine disruption. However, the utility and necessity of this chemical in consumer products has not been demonstrated in most cases. SUMMARY: Triclosan and the other examples provided show that a changing marketplace with little regulatory oversight of chemical uses can lead to unanticipated exposures and potential health risks to children. PMID- 26867166 TI - Environmental exposure to metals, neurodevelopment, and psychosis. AB - PURPOSE OF REVIEW: This article presents a new hypothesis about the possible relation between early life exposure to metals and psychosis. We review limitations of available research, and discuss novel approaches to overcome previous methodological barriers. RECENT FINDINGS: Mechanistic studies suggest a possible association between excess lead, manganese, cadmium, arsenic, or copper, and zinc deficiency, and several biochemical disturbances related to psychosis, such as altered neurotransmitters levels, excitotoxicity, and inflammation. Furthermore, studies suggest that some metals (lead, manganese, cadmium excess, and zinc deficiency) are associated with schizophrenia or psychosis-related phenotype. However, previous studies had multiple methodological limitations. Importantly, metal exposure was often measured after disease development and seldom determined during critical developmental periods. Most studies fell short of depicting the exact timing of exposure and the change in exposure over time. Here, we propose several methods to overcome these methodological limitations. SUMMARY: There is a plausible role of early life exposure to metals in the cause of psychosis. Owing to methodological limitations in exposure measurement, this has not been well characterized. Considering the wide exposure to metals and the high cost of psychosis to society, this hypothesis should be rigorously examined. PMID- 26867167 TI - Comparison of glomerular filtration rate measured between anterior and posterior image processing using Gates' method in an ectopic pelvic kidney. AB - OBJECTIVE: The aim of this study was to evaluate the difference in measured glomerular filtration rate (GFR) of an ectopic pelvic kidney between anterior and posterior image processing using Gates' method of renal dynamic imaging. METHODS: A total of 10 patients were studied retrospectively, with a single ectopic kidney in the pelvic cavity and a contralateral kidney at its normal anatomical position confirmed by ultrasound, computed tomography, renal dynamic imaging, etc. All images of ectopic kidneys were processed, and GFRs were measured using anterior and posterior Gates' method of renal dynamic imaging, respectively. The contralateral normal kidney was only processed on posterior imaging. The total GFRant of one patient, which was equal to the sum of the GFR of a normal kidney on posterior imaging and the GFR of an ectopic kidney on anterior imaging, was compared with the total GFRpost of two kidneys on posterior imaging, with the GFRtwo-sample from the two-sample method, and with the estimated GFR in the Chronic Kidney Disease Epidemiology Collaboration equation. All correlation analyses were carried out between GFRs obtained from three methods, and all patients were followed up. For statistical analysis, nonparametric rank tests were used, Bland-Altman graphs were plotted. RESULTS: The mean GFR of the ectopic kidney on anterior imaging was 27.48+/-12.24 ml/min/1.73 m. It was higher than the GFR (10.71+/-4.74 ml/min/1.73 m) on posterior imaging (t=-2.803, P<0.05). There were statistical differences between the total GFRant and the total GFRtwo sample (Z=-2.295, P<0.05), between the total GFRant and the total GFRpost (Z=2.599, P<0.01), between the total GFRtwo-sample and the total GFRpost (Z= 2.191, P<0.05), and between the total GFRant and the estimated glomerular filtration rate (Z=-2.803, P<0.01). The bias of the total GFRant was different from that of the total GFRpost (Z=-2.191, P<0.05). There were no differences in the precision and accuracy within 30% of the total GFRant and that of the total GFRpost (precision: F=0.351, P>0.05), but there were statistical differences in the accuracy within 10% of the total GFRant and that of the total GFRpost (P<0.05). CONCLUSION: The GFR measured using Gates' method of anterior image processing was more accurate than the GFR obtained on posterior image processing in reflecting the function of an ectopic pelvic kidney in renal dynamic imaging. PMID- 26867168 TI - Alcohol Lowers Your (Intestinal) Inhibitions. AB - Alcohol causes microbiota dysbiosis and breaches intestinal integrity, resulting in liver inflammation and ultimately cirrhosis. In this issue of Cell Host & Microbe, Wang et al. (2016) demonstrate that ethanol suppresses the intestinal anti-microbial response. This enables gut bacteria to trespass to the liver and thus exacerbates the disease progression. PMID- 26867169 TI - Microbes without Borders: Decompartmentalization of the Aging Gut. AB - The microbiota supports intestinal homeostasis in developing animals. With increased age, gut maintenance declines and microbes can stray from traditional zones, negatively impacting host health. In this issue of Cell Host & Microbe, Li et al. (2016) detail the mechanisms leading to the decline in intestinal health in aged flies. PMID- 26867170 TI - CRISPR-Cas Gatekeeper: Slow on the Uptake but Gets the Job Done. AB - Microbial CRISPR-Cas acts as a defense, but also as a gatekeeper controlling the flow of new genes into microbial genomes. In a recent Cell paper, Jiang et al. (2016) uncover the functional importance of transcription-dependent RNA targeting in type III-A CRISPR-Cas antiviral defense and provide insight into the co evolution of virus-host symbioses. PMID- 26867171 TI - The Avian Influenza Virus Polymerase Brings ANP32A Home to Roost. AB - Avian influenza virus polymerases function poorly in mammals, restricting transmission across species and the emergence of pandemic outbreaks. Long et al. (2016) have now identified ANP32A as a crucial cellular protein that dictates species-specific polymerase activity. PMID- 26867172 TI - SARS-CoV and IFN: Too Little, Too Late. AB - Dysregulated type I interferon (IFN-I) expression can lead to severe pathology and disease. In this issue of Cell Host & Microbe, Channappanavar et al. (2016) use a SARS-coronavirus animal model to describe how rapid and robust virus replication with delayed IFN-I can lead to lung immunopathology, with fatal outcomes. PMID- 26867173 TI - The Evolution of Antiviral Defense Systems. AB - Self-replicating genetic material presumably provided the architecture necessary for generating the last universal ancestor of all nucleic-acid-based life. As biological complexity increased in the billions of years that followed, the same genetic material also morphed into a wide spectrum of viruses and other parasitic genetic elements. The resulting struggle for existence drove the evolution of host defenses, giving rise to a perpetual arms race. This Perspective summarizes the antiviral mechanisms evident across the tree of life, discussing each in their evolutionary context to postulate how the coevolution of host and pathogen shaped the cellular antiviral defenses we know today. PMID- 26867174 TI - The cGAS-STING Defense Pathway and Its Counteraction by Viruses. AB - Upon virus infection, host cells mount a concerted innate immune response involving type I interferon and pro-inflammatory cytokines to enable elimination of the pathogen. Recently, cGAS and STING have been identified as intracellular sensors that activate the interferon pathway in response to virus infection and thus mediate host defense against a range of DNA and RNA viruses. Here we review how viruses are sensed by the cGAS-STING signaling pathway as well as how viruses modulate this pathway. Mechanisms utilized by viral proteins to inhibit cGAS and/or STING are also discussed. On the flip side, host cells have also evolved strategies to thwart viral immune escape. The balance between host immune control and viral immune evasion is pivotal to viral pathogenesis, and we discuss this virus-host stand-off in the context of the cGAS-STING innate immune pathway. PMID- 26867175 TI - The Interaction between Respiratory Pathogens and Mucus. AB - The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus. PMID- 26867176 TI - Selective Bottlenecks Shape Evolutionary Pathways Taken during Mammalian Adaptation of a 1918-like Avian Influenza Virus. AB - Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA) and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a "loose" bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses. PMID- 26867179 TI - Plant TRAF Proteins Regulate NLR Immune Receptor Turnover. AB - In animals, Tumor necrosis factor receptor-associated factor (TRAF) proteins are molecular adaptors that regulate innate and adaptive immunity, development, and abiotic stress responses. Although gene families encoding TRAF domain-containing proteins exhibit enriched diversity in higher plants, their biological roles are poorly defined. Here, we report the identification of two redundant TRAF proteins, Mutant, snc1-enhancing 13 (MUSE13) and MUSE14, that contribute to the turnover of nucleotide-binding domain and leucine-rich repeat-containing (NLR) immune receptors SNC1 and RPS2. Loss of both MUSE13 and MUSE14 leads to enhanced pathogen resistance, NLR accumulation, and autoimmunity, while MUSE13 overexpression results in reduced NLR levels and activity. In planta, MUSE13 associates with SNC1, RPS2, and the E3 ubiquitin ligase SCF(CPR1). Taken together, we speculate that MUSE13 and MUSE14 associate with the SCF E3 ligase complex to form a plant-type TRAFasome, which modulates ubiquitination and subsequent degradation of NLR immune sensors to maintain their homeostasis. PMID- 26867177 TI - Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. AB - Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage, and impaired virus-specific T cell responses. Genetic ablation of the IFN-alphabeta receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses. PMID- 26867178 TI - Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia. AB - Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me" signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia. PMID- 26867180 TI - A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP. AB - Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3 deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it. PMID- 26867181 TI - Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation. AB - Approximately half of all deaths from liver cirrhosis, the tenth leading cause of mortality in the United States, are related to alcohol use. Chronic alcohol consumption is accompanied by intestinal dysbiosis and bacterial overgrowth, yet little is known about the factors that alter the microbial composition or their contribution to liver disease. We previously associated chronic alcohol consumption with lower intestinal levels of the antimicrobial-regenerating islet derived (REG)-3 lectins. Here, we demonstrate that intestinal deficiency in REG3B or REG3G increases numbers of mucosa-associated bacteria and enhances bacterial translocation to the mesenteric lymph nodes and liver, promoting the progression of ethanol-induced fatty liver disease toward steatohepatitis. Overexpression of Reg3g in intestinal epithelial cells restricts bacterial colonization of mucosal surfaces, reduces bacterial translocation, and protects mice from alcohol-induced steatohepatitis. Thus, alcohol appears to impair control of the mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease. PMID- 26867184 TI - Prediction and prevention of hypertension-related events. PMID- 26867183 TI - Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism. AB - Pandemic influenza viruses modulate proinflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites, and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Proinflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses. PMID- 26867185 TI - Parents' attitudes toward genetic research in autism spectrum disorder. AB - OBJECTIVE: Genetic research in autism spectrum disorder (ASD) is mainly performed in minors who are legally unable to provide consent. Thus, knowledge of the attitudes, fears, and expectations toward genetic research of the parents is important. Knowledge of the attitudes toward genetic research will improve cooperation between researchers and participants, and help establish confidence in ASD genetic research. The present study aimed to assess these attitudes. MATERIALS AND METHODS: Questionnaire-based assessments of attitudes toward genetic research and toward procedures in genetic research of n=1455 parents of individuals with ASD were performed. RESULTS: The main motivation for participation in genetic research is to gain more knowledge of the causes and disease mechanisms of ASD (83.6%), and to contribute toward development of improved treatment in the future (63.7%). The parents also had a positive attitude towards storing genetic information (54.3%) and they requested confidentiality of data (82.9%) and expressed a need to be informed about the purpose (89%) and progress of the research (83.7%). We found a slightly more positive attitude to participation in genetic research among older parents (P=0.015), among fathers compared with mothers (P=0.01), among parents of girls compared with boys (P=0.03), and infantile autism compared with Asperger syndrome (P=0.002). However, linear regression analysis showed that parent and child characteristics seem to have too small an influence on attitudes toward genetic research to be of any relevance (R(2)=0.002-0.02). CONCLUSION: Parents of children with ASD have, in general, a very positive attitude toward genetic research. Data confidentiality is important, and they express a need for information on the purpose and progress of the research. PMID- 26867182 TI - Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan. AB - Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID- 26867186 TI - Transcriptional response of yellow perch to changes in ambient metal concentrations-A reciprocal field transplantation experiment. AB - Recent local adaptation to pollution has been evidenced in several organisms inhabiting environments heavily contaminated by metals. Nevertheless, the molecular mechanisms underlying adaptation to high metal concentrations are poorly understood, especially in fishes. Yellow perch (Perca flavescens) populations from lakes in the mining area of Rouyn-Noranda (QC, Canada) have been faced with metal contamination for about 90 years. Here, we examine gene transcription patterns of fish reciprocally transplanted between a reference and a metal-contaminated lake and also fish caged in their native lake. After four weeks, 111 genes were differentially transcribed in metal-naive fish transferred to the metal-contaminated lake, revealing a plastic response to metal exposure. Genes involved in the citric cycle and beta-oxidation pathways were under transcribed, suggesting a potential strategy to mitigate the effects of metal stress by reducing energy turnover. However, metal-contaminated fish transplanted to the reference lake did not show any transcriptomic response, indicating a reduced plastic response capability to sudden reduction in metal concentrations. Moreover, the transcription of other genes, especially ones involved in energy metabolism, was affected by caging. Overall, our results highlight environmental stress response mechanisms in yellow perch at the transcriptomic level and support a rapid adaptive response to metal exposure through genetic assimilation. PMID- 26867187 TI - Behavioural toxicity assessment of silver ions and nanoparticles on zebrafish using a locomotion profiling approach. AB - Zebrafish (Danio rerio) is not only a widely used species in the Fish Embryo Toxicity (FET) test but also an emerging model in behavioural ecotoxicology. By using automatic behaviour tracking technology, locomotion of developing zebrafish (ZF) larvae can be accurately recorded and potentially used in an ecotoxicological context to detect toxicant-induced behavioural alterations. In this study, we explored if and how quantitative locomotion data can be used for sub-lethal toxicity testing within the FET framework. We exposed ZF embryos to silver ions and nanoparticles, which previously have been reported to cause neurodevelopmental toxicity and behavioural retardation in early-life stages of ZF. Exposure to a broad range of silver (Ag(+) and AgNPs) concentrations was conducted, and developmental toxicity was assessed using FET criteria. For behavioural toxicity assessment, locomotion of exposed ZF eleutheroembryos (120hpf) was quantified according to a customised behavioural assay in an automatic video tracking system. A set of repeated episodes of dark/light stimulation were used to artificially stress ZF and evoke photo-motor responses, which were consequently utilized for locomotion profiling. Our locomotion-based behaviour profiling approach consisted of (1) dose-response ranking for multiple and single locomotion variables; (2) quantitative assessment of locomotion structure; and (3) analysis of ZF responsiveness to darkness stimulation. We documented that both silver forms caused adverse effects on development and inhibited hatchability and, most importantly, altered locomotion. High Ag(+) and AgNPs exposures significantly suppressed locomotion and a clear shift in locomotion towards inactivity was reported. Additionally, we noted that low, environmentally relevant Ag(+) concentrations may cause subordinate locomotive changes (hyperactivity) in developing fish. Overall, it was concluded that our locomotion-based behaviour-testing scheme can be used jointly with FET and can provide endpoints for sub-lethal toxicity. When combined with multivariate data analysis, this approach facilitated new insights for handling and analysis of data generated by automatized behavioural tracking systems. PMID- 26867188 TI - Design, Synthesis, and Biological Evaluation of Some Novel Pyrrolizine Derivatives as COX Inhibitors with Anti-Inflammatory/Analgesic Activities and Low Ulcerogenic Liability. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed anti-inflammatory and pain relief medications. However, their use is associated with many drawbacks, including mainly serious gastric and renal complications. In an attempt to circumvent these risks, a set of N-(4-bromophenyl)-7-cyano-6 substituted-H-pyrrolizine-5-carboxamide derivatives were designed, synthesized and evaluated as dual COX/5-LOX inhibitors. The structural elucidation, in vivo anti-inflammatory and analgesic activities using a carrageenan-induced rat paw edema model and hot plate assay, were performed, respectively. From the results obtained, it was found that the newly synthesized pyrrolizines exhibited IC50 values in the range of 2.45-5.69 uM and 0.85-3.44 uM for COX-1 and COX-2, respectively. Interestingly, compounds 12, 13, 16 and 17 showed higher anti inflammatory and analgesic activities compared to ibuprofen. Among these derivatives, compounds 16 and 19 displayed better safety profile than ibuprofen in acute ulcerogenicity and histopathological studies. Furthermore, the docking studies revealed that compound 17 fits nicely into COX-1 and COX-2 binding sites with the highest binding affinity, while compound 16 exerted the highest binding affinity for 5-LOX. In light of these findings, these novel pyrrolizine-5 carboxamide derivatives represent a promising scaffold for further development into potential dual COX/5-LOX inhibitors with safer gastric profile. PMID- 26867189 TI - Biological Activity of Vegetal Extracts Containing Phenols on Plant Metabolism. AB - The influence of vegetal extracts derived from red grape, blueberry fruits and hawthorn leaves on Zea mays L. plant growth and the activity of phenylalanine ammonia-lyase (PAL), a key enzyme of the phenylpropanoid pathway, was investigated in laboratory experiments. The extracts were characterized using FT IR and Raman spectroscopies in order to obtain a pattern of the main functional groups. In addition, phenols content was determined by HPLC, whereas the content of indoleacetic acid and isopentenyladenosine hormones was determined by ELISA test and the auxin and gibberellin-like activities by plant-bioassays. The treated maize revealed increased root and leaf biomass, chlorophyll and sugars content with respect to untreated plants. Hawthorn, red grape skin and blueberry at 1.0 mL/L induced high p-coumaric content values, whilst hawthorn also showed high amounts of gallic and p-hydroxybenzoic acids. PAL activity induced by hawthorn at 1.0 mL/L had the highest values (11.1-fold UNT) and was strongly and linearly related with the sum of leaf phenols. Our results suggest that these vegetal extracts contain more than one group of plant-promoting substances. PMID- 26867190 TI - Identification and Determination of the Polyhydroxylated Alkaloids Compounds with alpha-Glucosidase Inhibitor Activity in Mulberry Leaves of Different Origins. AB - Mulberry leaves have commonly been utilized in China as a herbal medicine for the treatment of diabetes for thousands of years. To evaluate the quality, an ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) method was developed for identification of polyhydroxylated alkaloids with alpha-glucosidase inhibitor activity in mulberry leaf. As a result, five alkaloid compounds were identified or tentatively characterized. Among them, the compound 1-deoxynojirimycin (DNJ) was selected as the most typical and active chemical marker and quantified using an improved high performance liquid chromatography (HPLC) normal phase coupled with evaporative light scattering detector (ELSD) method. The developed method was fully validated in terms of linearity, sensitivity, precision and repeatability, as well as recovery, and subsequently applied to evaluate twenty-nine batches of mulberry leaves from different collections. From the analytical data it was discovered that the average content of DNJ is 1.53 mg/g, while the total contents of DNJ in the 29 mulberry leaf sample ranged from 0.20 to 3.88 mg/g, which suggested remarkable differences, although it reached the highest levels in early August. These data may provide an important reference for the quality of mulberry leaves used as herbal medicine for the treatment of diabetes or as a material to obtain the DNJ of alpha-glucosidase inhibitor or as a functional food. PMID- 26867191 TI - Organic Nanomaterials and Their Applications in the Treatment of Oral Diseases. AB - There is a growing interest in the development of organic nanomaterials for biomedical applications. An increasing number of studies focus on the uses of nanomaterials with organic structure for regeneration of bone, cartilage, skin or dental tissues. Solid evidence has been found for several advantages of using natural or synthetic organic nanostructures in a wide variety of dental fields, from implantology, endodontics, and periodontics, to regenerative dentistry and wound healing. Most of the research is concentrated on nanoforms of chitosan, silk fibroin, synthetic polymers or their combinations, but new nanocomposites are constantly being developed. The present work reviews in detail current research on organic nanoparticles and their potential applications in the dental field. PMID- 26867192 TI - Comparative Evaluation of Total Antioxidant Capacities of Plant Polyphenols. AB - Thirty-seven samples of naturally occurring phenolic compounds were evaluated using three common in vitro assays for total antioxidant activity (TAC) testing: the Trolox Equivalent Antioxidant Capacity (TEAC), the Ferric Reducing Antioxidant Potential (FRAP) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, in addition to the Folin-Ciocalteu reagent reactivity (FCR). We found that antioxidant hierarchies depended on the choice of assay and applied ANOVA analyses to explore underlying structure-TAC dependencies. In addition to statistically confirming the empirically established connection between flavonoid ring-B catechol and high TEAC or FRAP, new correlations were also found. In flavonoids, (i) hydroxyl groups on ring-B had a positive effect on all four TAC assays; (ii) the presence of a 3-hydroxyl group on ring-C increased TEAC and FRAP, but had no effect on DPPH or FCR; (iii) Phenolic acids lacking a 3-hydroxyl group had significantly lower FRAP or DPPH than compounds having this structure, while TEAC or FCR were not affected. Results demonstrated that any TAC-based ranking of phenolic rich samples would very much depend on the choice of assay, and argue for use of more than one technique. As an illustration, we compared results of the above four assays using either grapevine leaf extracts or synthetic mixtures of compounds prepared according to major polyphenols identified in the leaves. PMID- 26867193 TI - Identification of Novel Pathways in Plant Lectin-Induced Cancer Cell Apoptosis. AB - Plant lectins have been investigated to elucidate their complicated mechanisms due to their remarkable anticancer activities. Although plant lectins seems promising as a potential anticancer agent for further preclinical and clinical uses, further research is still urgently needed and should include more focus on molecular mechanisms. Herein, a Naive Bayesian model was developed to predict the protein-protein interaction (PPI), and thus construct the global human PPI network. Moreover, multiple sources of biological data, such as smallest shared biological process (SSBP), domain-domain interaction (DDI), gene co-expression profiles and cross-species interolog mapping were integrated to build the core apoptotic PPI network. In addition, we further modified it into a plant lectin induced apoptotic cell death context. Then, we identified 22 apoptotic hub proteins in mesothelioma cells according to their different microarray expressions. Subsequently, we used combinational methods to predict microRNAs (miRNAs) which could negatively regulate the abovementioned hub proteins. Together, we demonstrated the ability of our Naive Bayesian model-based network for identifying novel plant lectin-treated cancer cell apoptotic pathways. These findings may provide new clues concerning plant lectins as potential apoptotic inducers for cancer drug discovery. PMID- 26867194 TI - Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples. AB - Three sets of polymerase chain reaction (PCR) primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap) cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV) assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine. PMID- 26867196 TI - A Quantum Cascade Laser-Based Optical Sensor for Continuous Monitoring of Environmental Methane in Dunkirk (France). AB - A room-temperature continuous-wave (CW) quantum cascade laser (QCL)-based methane (CH4) sensor operating in the mid-infrared near 8 MUm was developed for continuous measurement of CH4 concentrations in ambient air. The well-isolated absorption line (7F2,4 <- 8F1,2) of the nu4 fundamental band of CH4 located at 1255.0004 cm(-1) was used for optical measurement of CH4 concentration by direct absorption in a White-type multipass cell with an effective path-length of 175 m. A 1sigma (SNR = 1) detection limit of 33.3 ppb in 218 s was achieved with a measurement precision of 1.13%. The developed sensor was deployed in a campaign of measurements of time series CH4 concentration on a site near a suburban traffic road in Dunkirk (France) from 9th to 22nd January 2013. An episode of high CH4 concentration of up to ~3 ppm has been observed and analyzed with the help of meteorological parameters combined with back trajectory calculation using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model of NOAA. PMID- 26867197 TI - A Unified Global Reference Frame of Vertical Crustal Movements by Satellite Laser Ranging. AB - Crustal movement is one of the main factors influencing the change of the Earth system, especially in its vertical direction, which affects people's daily life through the frequent occurrence of earthquakes, geological disasters, and so on. In order to get a better study and application of the vertical crustal movement,as well as its changes, the foundation and prerequisite areto devise and establish its reference frame; especially, a unified global reference frame is required. Since SLR (satellite laser ranging) is one of the most accurate space techniques for monitoring geocentric motion and can directly measure the ground station's geocentric coordinates and velocities relative to the centre of the Earth's mass, we proposed to take the vertical velocity of the SLR technique in the ITRF2008 framework as the reference frame of vertical crustal motion, which we defined as the SLR vertical reference frame (SVRF). The systematic bias between other velocity fields and the SVRF was resolved by using the GPS (Global Positioning System) and VLBI (very long baseline interferometry) velocity observations, and the unity of other velocity fields and SVRF was realized,as well. The results show that it is feasible and suitable to take the SVRF as a reference frame, which has both geophysical meanings and geodetic observations, so we recommend taking the SLR vertical velocity under ITRF2008 as the global reference frame of vertical crustal movement. PMID- 26867195 TI - Therapeutic Effect of Losartan, an Angiotensin II Type 1 Receptor Antagonist, on CCl4-Induced Skeletal Muscle Injury. AB - TGF-beta1 is known to inhibit muscle regeneration after muscle injury. However, it is unknown if high systemic levels of TGF-beta can affect the muscle regeneration process. In the present study, we demonstrated the effect of a CCl4 intra-peritoneal injection and losartan (an angiotensin II type 1 receptor antagonist) on skeletal muscle (gastrocnemius muscle) injury and regeneration. Male C57BL/6 mice were grouped randomly as follows: control (n = 7), CCl4 treatment group (n = 7), and CCl4 + losartan treatment group (n = 7). After CCl4 treatment for a 16-week period, the animals were sacrificed and analyzed. The expression of dystrophin significantly decreased in the muscle tissues of the control group, as compared with that of the CCl4 + losartan group (p < 0.01). p(phospho)-Smad2/3 expression significantly increased in the muscles of the control group compared to that in the CCl4 + losartan group (p < 0.01). The expressions of Pax7, MyoD, and myogenin increased in skeletal muscles of the CCl4 + losartan group compared to the corresponding levels in the control group (p < 0.01). We hypothesize that systemically elevated TGF-beta1 as a result of CCl4 induced liver injury causes skeletal muscle injury, while losartan promotes muscle repair from injury via blockade of TGF-beta1 signaling. PMID- 26867198 TI - Viruses Causing Gastroenteritis: The Known, The New and Those Beyond. AB - The list of recently discovered gastrointestinal viruses is expanding rapidly. Whether these agents are actually involved in a disease such as diarrhea is the essential question, yet difficult to answer. In this review a summary of all viruses found in diarrhea is presented, together with the current knowledge about their connection to disease. PMID- 26867199 TI - Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge. AB - Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase >=3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 +/- 11.7 years, BMI 22.4 +/- 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 +/- 11.0 years, BMI 22.3 +/- 4.0) reported a symptomatic improvement (VAS score 2.3 +/- 1.2 vs. 6.5 +/- 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 +/- 12.7 years, BMI 22.0 +/- 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS. PMID- 26867202 TI - The protective effect of dopamine against OGD/R injury-induced cell death in HT22 mouse hippocampal cells. AB - Previous studies have shown that levo-dopamine (L-dopa) can improve the consciousness of certain patients with prolonged coma after cerebral ischemia reperfusion injury, and promote cell growth in vivo. This study aimed to investigate whether L-dopa, which is used clinically to treat Parkinson's disease, might also ameliorate ischemia-reperfusion injury-induced cell death. The oxygen-glucose deprivation and re-oxygenation (OGD/R) model was used to mimic the ischemia-reperfusion pathological process in vitro. HT22 cells were treated with dopamine hydrochloride at different times (i.e., 2 h prior to OGD, during the period of OGD, during the period of R, and throughout the period of OGD/R) and at different concentrations (i.e., 25 MUM, 50 MUM, 100 MUM). Lactate dehydrogenase (LDH) release, flow cytometry-annexin V, and propidium iodide staining with light microscopy showed that dopamine hydrochloride (added during re-oxygenation) promoted cell proliferation and facilitated maintenance of normal cell morphology. However, when present during oxygen-glucose deprivation for 18 h and present throughout OGD/R, dopamine hydrochloride increased cell damage as manifested by shrinkage, rounding up, and reduced viability. In conclusion, dopamine protected HT22 cells from OGD/R injury-induced cell death only at a particular point in time, suggesting that it may be useful for treating severe ischemia-reperfusion brain injury. PMID- 26867200 TI - DHA Supplementation Alone or in Combination with Other Nutrients Does not Modulate Cerebral Hemodynamics or Cognitive Function in Healthy Older Adults. AB - A number of recent trials have demonstrated positive effects of dietary supplementation with the omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on measures of cognitive function in healthy young and older adults. One potential mechanism by which EPA, and DHA in particular, may exert these effects is via modulation of cerebral hemodynamics. In order to investigate the effects of DHA alone or provided as one component of a multinutrient supplement (also including Gingko biloba, phosphatidylserine and vitamins B9 and B12) on measures of cerebral hemodynamics and cognitive function, 86 healthy older adults aged 50-70 years who reported subjective memory deficits were recruited to take part in a six month daily dietary supplementation trial. Relative changes in the concentration of oxygenated hemoglobin and deoxygenated hemoglobin were assessed using Near Infrared Spectroscopy (NIRS) during the performance of cognitive tasks prior to and following the intervention period. Performance on the cognitive tasks was also assessed. No effect of either active treatment was found for any of the NIRS measures or on the cognitive performance tasks, although the study was limited by a number of factors. Further work should continue to evaluate more holistic approaches to cognitive aging. PMID- 26867201 TI - Cardiometabolic Health in Submariners Returning from a 3-Month Patrol. AB - Confined space, limited exercise equipment, rotating shift work and reduced sleep may affect cardiometabolic health in submariners. To test this hypothesis, 53 male U.S. Submariners (20-39 years) were studied before and after a 3-month routine submarine patrol. Measures included anthropometrics, dietary and physical activity, biomarkers of cardiometabolic health, energy and appetite regulation, and inflammation. Before deployment, 62% of submariners had a body fat % (BF%) >= 25% (obesity), and of this group, 30% met the criteria for metabolic syndrome. In obese volunteers, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), leptin, the leptin/adiponectin ratio, and pro-inflammatory chemokines growth-related oncogene and macrophage-derived chemokine were significantly higher compared to non-obese submariners. Following the patrol, a significant mean reduction in body mass (5%) and fat-mass (11%) occurred in the obese group as a result of reduced energy intake (~2000 kJ) during the patrol; and, independent of group, modest improvements in serum lipids and a mean reduction in interferon gamma-induced protein 10 and monocyte chemotactic protein 1 were observed. Since 43% of the submariners remained obese, and 18% continued to meet the criteria for metabolic syndrome following the patrol, the magnitude of weight loss was insufficient to completely abolish metabolic dysfunction. Submergence up to 3-months, however, does not appear to be the cause of obesity, which is similar to that of the general population. PMID- 26867203 TI - Ultrasound-Guided Radiofrequency Denervation of the Medial Calcaneal Nerve. AB - OBJECTIVE: Plantar fasciosis is a common complaint of athletes, particularly for runners. The medial calcaneal nerve (MCN) may play a role in the pain syndrome, and radiofrequency (RF) denervation has been previously reported. The hypothesis is that ultrasound-guided denervation of the MCN results in symptomatic improvement. DESIGN: Retrospective cohort. SETTING: Private practice. PATIENTS: Twenty-nine patients previously receiving ultrasound-guided RF denervation of the MCN, having failed conservative therapy, were assessed in 2 groups, those more than (group 1, n = 16) or less than (group 2, n = 13) 6 months since the procedure. INTERVENTIONS: Ultrasound-guided RF denervation of the MCN. MAIN OUTCOME MEASURES: Pain scores before denervation, as well as at maximal pain relief and the time of the interview. Levels of satisfaction and attitudes toward surgery were also assessed. RESULTS: Pain scores decreased significantly in both groups, for both best and residual pain scores. Group 1 mean pain scores were 8.56 before procedure, 2.81 (P < 0.001 compared to baseline) at best pain score, and 3.75 (P < 0.01) residual pain score. Group 2 mean pain scores were 7.23 before procedure, 3.77 (P < 0.01) at best pain score and 4.92 (P < 0.01) residual pain score. Levels of satisfaction were predominantly positive (69% of group 1% and 54% of group 2 were either somewhat or very satisfied), with attitudes toward surgery unchanged. CONCLUSIONS: For patients with refractory plantar heel pain, ultrasound-guided denervation of the MCN can potentially improve symptoms, although efficacy needs assessing in comparative studies. CLINICAL RELEVANCE: Ultrasound-guided denervation of the MCN provides a further management option for patients with refractory plantar fasciosis. PMID- 26867204 TI - Googling Concussion Care: A Critical Appraisal of Online Concussion Healthcare Providers and Practices in Canada. AB - BACKGROUND: Concussion is an emerging public health concern, but care of patients with a concussion is presently unregulated in Canada. METHODS: Independent, blinded Google Internet searches were conducted for the terms "concussion" and "concussion clinic" and each of the Canadian provinces and territories. The first 10 to 15 concussion healthcare providers per province were identified. A critical appraisal of healthcare personnel and services offered on the provider's Web site was conducted. RESULTS: Fifty-eight concussion healthcare providers were identified using this search methodology. Only 40% listed the presence of an on site medical doctor (M.D.) as a member of the clinical team. Forty-seven percent of concussion healthcare providers advertised access to a concussion clinic, program, or center on their Web site. Professionals designated as team leaders, directors, or presidents among concussion clinics, programs, and centers included a neuropsychologist (15%), sports medicine physician (7%), neurologist (4%), and neurosurgeon (4%). Services offered by providers included baseline testing (67%), physiotherapy (50%), and hyperbaric oxygen therapy (2%). CONCLUSIONS: This study indicates that there are numerous concussion healthcare providers in Canada offering diverse services with clinics operated by professionals with varying levels of training in traumatic brain injury. In some cases, the practices of these concussion clinics do not conform to current expert consensus guidelines. PMID- 26867205 TI - Optical and positron annihilation spectroscopic studies on PMMA polymer doped by rhodamine B/chloranilic acid charge transfer complex: Special relevance to the effect of gamma-ray irradiation. AB - Polymeric sheets of poly (methylmethaclyerate) (PMMA) containing charge transfer (CT) complex of rhodamine B/chloranilic acid (Rho B/CHA) were synthesized in methanol solvent at room temperature. The systematic analysis done on the Rho B and its CT complex in the form of powder or polymeric sheets confirmed their structure and thermal stability. The IR spectra interpreted the charge transfer mode of interaction between the CHA central positions and the terminal carboxylic group. The polymer sheets were irradiated with 70 kGy of gamma radiation using (60)Co source to study the enhanced changes in the structure and optical parameters. The microstructure changes of the PMMA sheets caused by gamma-ray irradiation were analyzed using positron annihilation lifetime (PAL) and positron annihilation Doppler broadening (PADB) techniques. The positron life time components (tau(i)) and their corresponding intensities (I(i)) as well as PADB line-shape parameters (S and W) were found to be highly sensitive to the enhanced disorder occurred in the organic chains of the polymeric sheets due to gamma irradiation. PMID- 26867206 TI - Short duration response-guided treatment is effective for most individuals with recent hepatitis C infection: the ATAHC II and DARE-C I studies. AB - BACKGROUND: Individuals with recent HCV infection may benefit from shortened duration therapy. These studies evaluated the efficacy and safety of response guided regimens with pegylated interferon-alpha2a and ribavirin for people with recent HCV infection. METHODS: Participants with recent hepatitis C (duration of infection <=18 months) enrolled in the ATAHC II (pegylated interferon-alpha2a +/- ribavirin) and DARE-C I (pegylated interferon-alpha2a, ribavirin and telaprevir) studies were included for analysis. Treatment duration was response-guided (ATAHC II: 8, 16, 24 or 48 weeks; DARE-C I: 8, 12 or 24 weeks) and dependent on time to first undetectable HCV RNA using Roche Taqman HCV RNA testing. The primary efficacy end point was sustained virological response at 12 weeks (SVR12) by intention-to-treat. Logistic regression analyses were used to identify predictors of SVR. RESULTS: A total of 82 participants (62% HIV-positive) were enrolled in ATAHC II (treated, n=52) and 14 (79% HIV-positive) in DARE-C I. The predominant modes of HCV acquisition were injecting drug use (ATAHC II 55%, DARE-C I 36%) and sexual intercourse with a partner of the same sex (ATAHC II 39%, DARE-C I 64%). SVR12 was 71% in both ATAHC II (37/52) and DARE-C I (10/14) with 56% in ATAHC II receiving shortened therapy (8 or 16 weeks). SVR was associated with a rapid virological response (odds ratio 10.80; P=0.001). CONCLUSIONS: The majority of participants were able to receive short duration response-guided therapy with pegylated interferon-alpha2a and ribavirin. Response-guided therapy for recent hepatitis C infection could be considered in the absence of available interferon free therapies. ClinicalTrials.gov registry (ATAHC II: NCT01336010; DARE-C I: NCT01743521). PMID- 26867207 TI - Taming the fear of voice: Dilemmas in maintaining a high vaccination rate in the Netherlands. AB - In the context of international public debates on vaccination the National Institute for Public Health and the Environment (RIVM), the Dutch public health body responsible for the National Immunization Programme (NIP), fears that the high vaccination rate of children in the Netherlands obscures the many doubts and criticisms parents may have about vaccination. The question arises as to how the robustness of this vaccination rate and the resilience of the NIP can be assessed. To answer this question, we explore the vaccination practices and relationships between professionals and parents using qualitative methods. Drawing on Hirschman's concepts of exit, voice and loyalty, we distinguish between two different approaches to vaccination: one which enforces parental loyalty to the vaccination programme, and one which allows for voice. The analysis shows that due to their lack of voice in the main vaccination setting, parents' considerations are unknown and insight into their loyalty is lacking. We argue that the Dutch vaccination programme is caught between the insecurity of enforced parental loyalty to the NIP and the insecurity of enabling parental voice and negotiating space. We conclude that to increase the resilience of the NIP, experimenting with voice and exit is inevitable. PMID- 26867208 TI - The role of social support in protecting mental health when employed and unemployed: A longitudinal fixed-effects analysis using 12 annual waves of the HILDA cohort. AB - Perceived social support is associated with overall better mental health. There is also evidence that unemployed workers with higher social support cope better psychologically than those without such support. However, there has been limited research about the effect of social support among people who have experienced both unemployment and employment. We assessed this topic using 12 years of annually collected cohort data. The sample included 3190 people who had experienced both unemployment and employment. We used longitudinal fixed-effects modelling to investigate within-person changes in mental health comparing the role of social support when a person was unemployed to when they were employed. Compared to when a person reported low social support, a change to medium (6.35, 95% 5.66 to 7.04, p < 0.001) or high social support (11.58, 95%, 95% CI 10.81 to 12.36, p < 0.001) was associated with a large increase in mental health (measured on an 100 point scale, with higher scores representing better mental health). When a person was unemployed but had high levels of social support, their mental health was 2.89 points (95% CI 1.67 to 4.11, p < 0.001) higher than when they were employed but had lower social support. The buffering effect of social support was confirmed in stratified analysis. There was a strong direct effect of social support on mental health. The magnitude of these differences could be considered clinically meaningful. Our results also suggest that social support has a significant buffering effect on mental health when a person is unemployed. PMID- 26867209 TI - Healthy and unhealthy red blood cell detection in human blood smears using neural networks. AB - One of the most common diseases that affect human red blood cells (RBCs) is anaemia. To diagnose anaemia, the following methods are typically employed: an identification process that is based on measuring the level of haemoglobin and the classification of RBCs based on a microscopic examination in blood smears. This paper presents a proposed algorithm for detecting and counting three types of anaemia-infected red blood cells in a microscopic coloured image using circular Hough transform and morphological tools. Anaemia cells include sickle, elliptocytosis, microsite cells and cells with unknown shapes. Additionally, the resulting data from the detection process have been analysed by a prevalent data analysis technique: the neural network. The experimental results for this model have demonstrated high accuracy for analysing healthy/unhealthy cells. This algorithm has achieved a maximum detection of approximately 97.8% of all cells in 21 microscopic images. Effectiveness rates of 100%, 98%, 100%, and 99.3% have been achieved using neural networks for sickle cells, elliptocytosis cells, microsite cells and cells with unknown shapes, respectively. PMID- 26867210 TI - A study on the orientation inheritance in laminated NiAl produced by in situ reaction annealing. AB - In order to promote the performance of B2 NiAl by texture control of orientation during in situ processing, phase transformation in laminated NiAl with bimodal grain size distribution manufactured by reaction annealing of Ni and Al foils has been studied. It turned out that there existed a Kurdjumov-Sachs orientation relationship (K-S OR) between parent Ni and product NiAl by crystallography analysis according to the electron backscatter diffraction (EBSD) results. The parent Ni did not transform to the product NiAl directly but via the formation of Ni3Al firstly according to the transmission electron microscope (TEM) observation of the interface. This led to a new K-S OR between Ni3Al and NiAl with a small atomic misfit, which made less residual stress generated through the formation of Ni3Al than directly from the parent Ni. PMID- 26867211 TI - Minimal Increase Network Coding for Dynamic Networks. AB - Because of the mobility, computing power and changeable topology of dynamic networks, it is difficult for random linear network coding (RLNC) in static networks to satisfy the requirements of dynamic networks. To alleviate this problem, a minimal increase network coding (MINC) algorithm is proposed. By identifying the nonzero elements of an encoding vector, it selects blocks to be encoded on the basis of relationship between the nonzero elements that the controls changes in the degrees of the blocks; then, the encoding time is shortened in a dynamic network. The results of simulations show that, compared with existing encoding algorithms, the MINC algorithm provides reduced computational complexity of encoding and an increased probability of delivery. PMID- 26867212 TI - Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family. AB - O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O glycan functions. We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. These are all important functions of viral glycoproteins. These phenotypes were broadly conserved for equivalent NiV mutants. Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses. PMID- 26867213 TI - Leaf Mass per Area (LMA) and Its Relationship with Leaf Structure and Anatomy in 34 Mediterranean Woody Species along a Water Availability Gradient. AB - Leaf mass per area (LMA) is a morphological trait widely used as a good indicator of plant functioning (i.e. photosynthetic and respiratory rates, chemical composition, resistance to herbivory, etc.). The LMA can be broken down into the leaf density (LD) and leaf volume to area ratio (LVA or thickness), which in turn are determined by anatomical tissues and chemical composition. The aim of this study is to understand the anatomical and chemical characteristics related to LMA variation in species growing in the field along a water availability gradient. We determined LMA and its components (LD, LVA and anatomical tissues) for 34 Mediterranean (20 evergreen and 14 deciduous) woody species. Variation in LMA was due to variation in both LD and LVA. For both deciduous and evergreen species LVA variation was strongly and positively related with mesophyll volume per area (VA or thickness), but for evergreen species positive relationships of LVA with the VA of epidermis, vascular plus sclerenchyma tissues and air spaces were found as well. The leaf carbon concentration was positively related with mesophyll VA in deciduous species, and with VA of vascular plus sclerenchymatic tissues in evergreens. Species occurring at the sites with lower water availability were generally characterised by a high LMA and LD. PMID- 26867215 TI - Comprehensive Immunophenotypic Characterization of Adult and Fetal Testes, the Excretory Duct System, and Testicular and Epididymal Appendages. AB - The immunophenotype of a normal testis and the excretory duct system has not been studied comprehensively in fetal and adult patients without testicular disease or hormonal manipulation so far. In addition, testicular (TA) and epididymal (EA) appendages are frequent paratesticular structures without previously reported comprehensive immunophenotypic studies. Immunohistochemistry for multiple markers, including the androgen receptor (AR), the estrogen receptor (ER), the progesterone receptor (PR), the prostate-specific antigen, the prostate-specific membrane antigen, PAX8, WT1, calretinin, CK7, CK20, OCT4, SALL4, and CD117, was performed on full sections of testicular/paratesticular tissue from a large cohort of adult and fetal autopsy patients. In contrast to adult germ cells (GC), fetal GC strongly express OCT4 and CD117, although the expression of these proteins is lost in the early postnatal period; SALL4, in contrast, is expressed in both fetal and adult GC, with only weak and focal expression in adult patients. Fetal Sertoli cells (SC) express WT1 and calretinin strongly and diffusely, in contrast to adult SC. Both fetal and adult excretory duct systems express CK7 and PAX8 with frequent AR coexpression, and all 3 main segments of the excretory duct system (ductuli efferentes, epididymis, and vas deferens) have unique immunophenotypes. The rete testis also has a unique immunohistochemical expression pattern, which includes strong expression of CK7, PAX8, WT1, calretinin, and AR. Finally, of the adult autopsy patients examined, 80% had a TA, and 60% had an EA; these paratesticular structures occurred at stereotypical locations, demonstrated reproducible morphologic features, and had a unique immunophenotype relative to other studied structures, with strong CK7, PAX8, WT1, AR, ER, and PR coexpression. The testis and the paratestis may be involved by diverse neoplastic and non-neoplastic processes, and knowledge of the immunophenotypic expression spectrum of these tissues may aid in clinical diagnosis and advance our understanding of the pathogenesis of both oncologic and nononcologic disease processes. PMID- 26867214 TI - Hexose Oxidase-Mediated Hydrogen Peroxide as a Mechanism for the Antibacterial Activity in the Red Seaweed Ptilophora subcostata. AB - Marine algae have unique defense strategies against microbial infection. However, their mechanisms of immunity remain to be elucidated and little is known about the similarity of the immune systems of marine algae and terrestrial higher plants. Here, we suggest a possible mechanism underlying algal immunity, which involves hexose oxidase (HOX)-dependent production of hydrogen peroxide (H2O2). We examined crude extracts from five different red algal species for their ability to prevent bacterial growth. The extract from one of these algae, Ptilophora subcostata, was particularly active and prevented the growth of gram positive and -negative bacteria, which was completely inhibited by treatment with catalase. The extract did not affect the growth of either a yeast or a filamentous fungus. We partially purified from P. subcostata an enzyme involved in its antibacterial activity, which shared 50% homology with the HOX of red seaweed Chondrus crispus. In-gel carbohydrate oxidase assays revealed that P. subcostata extract had the ability to produce H2O2 in a hexose-dependent manner and this activity was highest in the presence of galactose. In addition, Bacillus subtilis growth was strongly suppressed near P. subcostata algal fronds on GYP agar plates. These results suggest that HOX plays a role in P. subcostata resistance to bacterial attack by mediating H2O2 production in the marine environment. PMID- 26867217 TI - Ten Simple Rules for Selecting a Bio-ontology. PMID- 26867216 TI - A New Mutation, hap1-2, Reveals a C Terminal Domain Function in AtMago Protein and Its Biological Effects in Male Gametophyte Development in Arabidopsis thaliana. AB - The exon-exon junction complex (EJC) is a conserved eukaryotic multiprotein complex that examines the quality of and determines the availability of messenger RNAs (mRNAs) posttranscriptionally. Four proteins, MAGO, Y14, eIF4AIII and BTZ, function as core components of the EJC. The mechanisms of their interactions and the biological indications of these interactions are still poorly understood in plants. A new mutation, hap1-2. leads to premature pollen death and a reduced seed production in Arabidopsis. This mutation introduces a viable truncated transcript AtMagoDeltaC. This truncation abolishes the interaction between AtMago and AtY14 in vitro, but not the interaction between AtMago and AteIF4AIII. In addition to a strong nuclear presence of AtMago, both AtMago and AtMagoDeltaC exhibit processing-body (P-body) localization. This indicates that AtMagoDeltaC may replace AtMago in the EJC when aberrant transcripts are to be degraded. When introducing an NMD mutation, upf3-1, into the existing HAP1/hap1-2 mutant, plants showed a severely reduced fertility. However, the change of splicing pattern of a subset of SR protein transcripts is mostly correlated with the sr45-1 and upf3-1 mutations, not the hap1-2 mutation. These results imply that the C terminal domain (CTD) of AtMago is required for the AtMago-AtY14 heterodimerization during EJC assembly, UPF3-mediated NMD pathway and the AtMago-AtY14 heterodimerization work synergistically to regulate male gametophyte development in plants. PMID- 26867219 TI - Voxel Based Analysis of Surgical Revascularization for Moyamoya Disease: Pre- and Postoperative SPECT Studies. AB - Moyamoya disease (MMD) is a chronic, progressive, cerebrovascular occlusive disease that causes abnormal enlargement of collateral pathways (moyamoya vessels) in the region of the basal ganglia and thalamus. Cerebral revascularization procedures remain the preferred treatment for patients with MMD, improving the compromised cerebral blood flow (CBF). However, voxel based analysis (VBA) of revascularization surgery for MMD based on data from pre- and postoperative data has not been established. The latest algorithm called as Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) has been introduced for VBA as the function of statistical parametric mapping (SPM8), and improved registration has been achieved by SPM8 with DARTEL. In this study, VBA was conducted to evaluate pre- and postoperative single photon emission computed tomography (SPECT) images for MMD by SPM8 with DARTEL algorithm, and the results were compared with those from SPM8 without DARTEL (a conventional method). Thirty-two patients with MMD who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery as the first surgery were included and all patients underwent pre- and postoperative 3D T1 weighted imaging and SPECT. Pre- and postoperative SPECT images were registered to 3D T1-weighted images, then VBA was conducted. Postoperative SPECT showed more statistically increased CBF areas in the bypassed side cerebral hemisphere by using SPM8 with DARTEL (58,989 voxels; P<0.001), and increased ratio of CBF after operation was less than 15%. Meanwhile, postoperative SPECT showed less CBF increased areas by SPM8 without DARTEL. In conclusion, VBA was conducted for patients with MMD, and SPM8 with DARTEL revealed that postoperative SPECT showed statistically significant CBF increases over a relatively large area and with at most 15% increase ratio. PMID- 26867218 TI - Distribution and Abundance of Glucocorticoid and Mineralocorticoid Receptors throughout the Brain of the Great Tit (Parus major). AB - The glucocorticoid stress response, regulated by the hypothalamic-pituitary adrenal (HPA) axis, enables individuals to cope with stressors through transcriptional effects in cells expressing the appropriate receptors. The two receptors that bind glucocorticoids-the mineralocorticoid receptor (MR) and glucocorticoid receptor (GR)-are present in a variety of vertebrate tissues, but their expression in the brain is especially important. Neural receptor patterns have the potential to integrate multiple behavioral and physiological traits simultaneously, including self-regulation of glucocorticoid secretion through negative feedback processes. In the present work, we quantified the expression of GR and MR mRNA throughout the brain of a female great tit (Parus major), creating a distribution map encompassing 48 regions. This map, the first of its kind for P. major, demonstrated a widespread but not ubiquitous distribution of both receptor types. In the paraventricular nucleus of the hypothalamus (PVN) and the hippocampus (HP)-the two brain regions that we sampled from a total of 25 birds, we found high GR mRNA expression in the former and, unexpectedly, low MR mRNA in the latter. We examined the covariation of MR and GR levels in these two regions and found a strong, positive relationship between MR in the PVN and MR in the HP and a similar trend for GR across these two regions. This correlation supports the idea that hormone pleiotropy may constrain an individual's behavioral and physiological phenotype. In the female song system, we found moderate GR in hyperstriatum ventrale, pars caudalis (HVC), and moderate MR in robust nucleus of the arcopallium (RA). Understanding intra- and interspecific patterns of glucocorticoid receptor expression can inform us about the behavioral processes (e.g. song learning) that may be sensitive to stress and stimulate future hypotheses concerning the relationships between receptor expression, circulating hormone concentrations and performance traits under selection, including behavior. PMID- 26867221 TI - Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves. AB - There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age. PMID- 26867220 TI - Non-Classical Monocytes and Monocyte Chemoattractant Protein-1 (MCP-1) Correlate with Coronary Artery Calcium Progression in Chronically HIV-1 Infected Adults on Stable Antiretroviral Therapy. AB - BACKGROUND: Persistent inflammation and immune activation has been hypothesized to contribute to increased prevalence of subclinical atherosclerosis and cardiovascular disease (CVD) risk in patients with chronic HIV infection. In this study, we examined the correlation of peripheral monocyte subsets and soluble biomarkers of inflammation to coronary artery calcium (CAC) progression, as measured by cardiac computed tomography scan. METHODS: We conducted a longitudinal analysis utilizing baseline data of 78 participants with HIV infection on stable antiretroviral therapy (ART) in the Hawaii Aging with HIV Cardiovascular study who had available baseline monocyte subset analysis as well as CAC measurement at baseline and at 2-year follow up. Monocyte phenotypes were assessed from cryopreserved blood by flow cytometry and plasma was assayed for soluble biomarkers using antibody-coated beads in a high sensitivity Milliplex Luminex platform. Change in CAC over 2 years was analyzed as the primary outcome variable. RESULTS: Of all monocyte subsets and biomarkers tested, higher non classical monocyte percentage (rho = 0.259, p = 0.022), interleukin (IL)-6 (rho = 0.311, p = 0.012), and monocyte chemoattractant protein (MCP)-1 (rho = 0.524, p = <0.001) were significantly correlated to higher 2-year CAC progression in unadjusted Spearman's correlation. Non-classical monocyte percentage (rho = 0.247, p = 0.039), and MCP-1 (rho = 0.487, p = <0.001), remained significantly correlated to 2-year CAC progression, while IL-6 was not (rho = 0.209, p = 0.120) after adjustment for age, hypertension, diabetes mellitus, total/HDL cholesterol ratio, smoking history, and BMI. CONCLUSION: The percentage of non-classical monocytes and plasma MCP-1 levels were independently associated with CAC progression and may be related to the progression of atherosclerosis and increased CVD risk associated with chronic HIV infection on stable ART. PMID- 26867222 TI - The Invasion of Coastal Areas in South China by Ipomoea cairica May Be Accelerated by the Ecotype Being More Locally Adapted to Salt Stress. AB - Local adaptation and phenotypic plasticity are two alternative mechanisms used by invasive plants for range expansion. We conducted a series of experiments to investigate the role of these mechanisms in the recent expansion of the invasive Ipomoea cairica from non-saline to salt-stressed coastal habitats. A comparison of the plant's photosynthetic traits and construction costs across habitats was conducted through a field survey. Meanwhile, a full factorial greenhouse experiment was conducted with two ecotypes (non-saline and coastal) of I. cairica and two salinity gradients (water and 4 g L-1 NaCl solution) to evaluate the roles of the two strategies by comparing their main traits. The results revealed that the construction cost and Amax of I. cairica did not change with the habitat type. The ecotype and saline treatments, however, significantly influenced the plant growth. The non-saline ecotype (NE) generally showed higher or equal plasticity of biomass-allocation and functional traits compared to the coastal ecotype (CE). However, the fitness and biomass of the NE significantly decreased with salinity, whereas those aspects of the CE did not change. Our results indicate that the recent expansion of I. cairica into coastal areas may be accelerated by the local adaptation of the CE to salt stress. Additionally, in South China, the CE will most likely evolve adaptations to both saline and non saline environments, which will further broaden the invasion range of I. cairica in the future. PMID- 26867224 TI - Cytotoxicity and effect on protease activity of copolymer extracts containing catechin. AB - OBJECTIVE: To evaluate cytotoxicity and effect on protease activity of epigallocatechin-gallate extracted from experimental restorative dental copolymers in comparison to the control compound chlorhexidine. METHODS: Copolymer disks were prepared from bis-GMA/TEGDMA (70/30 mol%) containing no compound (control) or 1% w/w of either epigallocatechin-gallate or chlorhexidine. MDPC-23 odontoblast-like cells were seeded with the copolymer extracts leached out into deionized water. Cell metabolic activity was quantified by 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at 24, 48, 72 h. Inhibition of protease activity by resin extracts was measured by a collagenolytic/genatinolytic enzyme activity assay and gelatin zymography. Data for MTT and protease inhibition were analyzed using two-way ANOVA followed by Tukey or Bonferroni post hoc tests (alpha=0.05). RESULTS: The MTT revealed that at 72 h, extracts from control (16.7%) and chlorhexidine (22.3%) copolymers induced significant reduction in cell metabolism (p<0.05). All copolymer extracts caused enzymatic inhibition in a dose dependent manner (p<0.01). Even when highly diluted, epigallocatechin-gallate extract had a significant antiproteolytic activity (p<0.05). Zymograms showed that all extracts reduced activity of MMP-2 and MMP-9 (pro- and active forms), with MMP-9 exhibiting the highest percentage inhibition revealed by densitometry. CONCLUSIONS: Epigallocatechin-gallate and chlorhexidine extracts did not exert cytotoxicity on evaluated cells when compared to control extracts. Both compounds retained antiproteolytic activity after extraction from a dental copolymer. CLINICAL SIGNIFICANCE: Once extracted from a dental copolymer, epigallocatechin-gallate is not cytotoxic and retains antiproteolytic activity. These results may allow incorporation of epigallocatechin-gallate as a natural-safe alternative to chlorhexidine in functionalized restorative materials. PMID- 26867223 TI - Late Presentation of Fulminant Necrotizing Enterocolitis in a Child with Hyperinsulinism on Octreotide Therapy. AB - Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. In cases of diazoxide-unresponsive HI, alternative medical and surgical approaches may be required to reduce the risk of hypoglycemia. Octreotide, a somatostatin analog, often has a role in the management of these children, but a dose-dependent reduction in splanchnic blood flow is a recognized complication. Necrotizing enterocolitis (NEC) has been reported within the first few weeks of initiating predominantly high doses of octreotide. We describe the case of an infant with Beckwith-Wiedemann syndrome and diazoxide-unresponsive HI, who had persistent hypoglycemia after two pancreatectomy surgeries. She developed NEC 2 months after beginning octreotide therapy at a relatively low dose of 8 ug/kg/day. This complication has occurred later, and at a lower dose, than has previously been described. We review the case and identify the known and suspected multifactorial risk factors for NEC that may contribute to the development of this complication in patients with HI. PMID- 26867225 TI - Effect of the association of maltodextrin and sucrose on the acidogenicity and adherence of cariogenic bacteria. AB - OBJECTIVE: The aim was to investigate the effect of maltodextrin and sucrose association on the acidogenic and adherence profiles of cariogenic bacteria. DESIGN: Streptococcus mutans (S. mutans) and Lactobacillus casei (L. casei) were cultivated in culture medium containing maltodextrin, sucrose, maltodextrin sucrose mixture or glucose. Analyses of the acidogenicity and microbial adherence were conducted in triplicate for each microorganism and tested carbohydrate. RESULTS: For L. casei, maltodextrin, sucrose and maltodextrin-sucrose mixture showed lower acidogenic potential compared to glucose. When the microorganism was S. mutans, sucrose and maltodextrin-sucrose mixture presented higher acidogenic potential compared to maltodextrin and glucose. Microbial adherence analysis revealed higher adherence for S. mutans in presence of sucrose and maltodextrin sucrose mixture compared to maltodextrin and glucose. For L. casei, all the carbohydrates showed similar adherence percentages. CONCLUSION: The addition of maltodextrin to sucrose does not increase the cariogenicity of sucrose in terms of acidogenicity and adherence of the cariogenic bacteria. PMID- 26867228 TI - The outlook for 2016. PMID- 26867227 TI - [Factors that influence comorbidity from panic disorder and PTSD after earthquakes]. AB - OBJECTIVE: After the earthquake and tsunami in Chile (F-27), we studied the effect of socio-demographic factors, exposure to the event, and state aid received on comorbidity from panic disorder (PD) and posttraumatic stress disorder (PTSD). METHOD: Surveys that include the administration of the Davidson Trauma Scale (DTS) to 246 inhabitants. RESULTS: 19.1 % comorbidity was found (r=.583, R(2)=.340, p<.01). Females homeowners have a higher risk of PD and PTSD. State aid is associated with more cases of PD. CONCLUSIONS: We designed risk/resistance profiles against earthquakes/tsunamis and an instrument to detect cases at risk of PTSD. We suggest guidelines so that the government can improve its role after disasters. PMID- 26867226 TI - Epidemiology and Burden of Bloodstream Infections Caused by Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae in a Pediatric Hospital in Senegal. AB - CONTEXT: Severe bacterial infections are not considered as a leading cause of death in young children in sub-Saharan Africa. The worldwide emergence of extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) could change the paradigm, especially in neonates who are at high risk of developing healthcare-associated infections. OBJECTIVE: To evaluate the epidemiology and the burden of ESBL-E bloodstream infections (BSI). METHODS: A case-case-control study was conducted in patients admitted in a pediatric hospital during two consecutive years. Cases were patients with Enterobacteriaceae BSI and included ESBL-positive (cases 1) and ESBL-negative BSI (cases 2). Controls were patients with no BSI. Multivariate analysis using a stepwise logistic regression was performed to identify risk factors for ESBL acquisition and for fatal outcomes. A multistate model was used to estimate the excess length of hospital stay (LOS) attributable to ESBL production while accounting for time of infection. Cox proportional hazards models were performed to assess the independent effect of ESBL-positive and negative BSI on LOS. RESULTS: The incidence rate of ESBL-E BSI was of 1.52 cases/1000 patient-days (95% CI: 1.2-5.6 cases per 1000 patient-days). Multivariate analysis showed that independent risk factors for ESBL-BSI acquisition were related to underlying comorbidities (sickle cell disease OR = 3.1 (95%CI: 2.3-4.9), malnutrition OR = 2.0 (95%CI: 1.7-2.6)) and invasive procedures (mechanical ventilation OR = 3.5 (95%CI: 2.7-5.3)). Neonates were also identified to be at risk for ESBL-E BSI. Inadequate initial antibiotic therapy was more frequent in ESBL-positive BSI than ESBL-negative BSI (94.2% versus 5.7%, p<0.0001). ESBL-positive BSI was associated with higher case-fatality rate than ESBL-negative BSI (54.8% versus 15.4%, p<0.001). Multistate modelling indicated an excess LOS attributable to ESBL production of 4.3 days. The adjusted end-of LOS hazard ratio for ESBL-positive BSI was 0.07 (95%CI, 0.04-0.12). CONCLUSION: Control of ESBL-E spread is an emergency in pediatric populations and could be achieved with simple cost-effective measures such as hand hygiene, proper management of excreta and better stewardship of antibiotic use, especially for empirical therapy. PMID- 26867229 TI - OPINION. Thoughts, views and your feedback. PMID- 26867230 TI - It's all about position. PMID- 26867231 TI - LISTEN UP. PMID- 26867232 TI - Communication matters. PMID- 26867233 TI - LIVING WITH MISCARRIAGE. PMID- 26867234 TI - Antidepressant use in late pregnancy. PMID- 26867235 TI - Barriers to facilitating birth in Nepal. PMID- 26867236 TI - Write a research proposal. PMID- 26867237 TI - Bullying. The writing on the wall. PMID- 26867239 TI - A day on the farm. PMID- 26867238 TI - Engaging in research. PMID- 26867240 TI - Remote control. PMID- 26867241 TI - PREVENTING PERTUSSIS. PMID- 26867242 TI - The voice of midwifery education. PMID- 26867243 TI - Doulas ... complementary or conflicting? PMID- 26867244 TI - Parental preparation. PMID- 26867245 TI - LEARNING leadership. PMID- 26867246 TI - BORN IN AFRICA. PMID- 26867247 TI - Tackling health inequality. PMID- 26867248 TI - Childhood Cancers in Zimbabwe: A 10 year review of the Zimbabwe National Cancer Registry data. AB - OBJECTIVE: To document the pattern of cancer in children (0-14 years) registered in the Zimbabwe National Cancer Registry from 2000-2009. DESIGN: Retrospective descriptive analysis. METHODS: Analysis of data from the Zimbabwe National Cancer Registry for the period 2000-2009. SETTING: The Zimbabwe National Cancer Registry. RESULTS: Childhood Cancer constituted 3.8% of all malignancies recorded at the cancer registry during the study period. The common cancers were: Wilm's Tumour 286 (16.2%), Kaposi Sarcoma 277 (15.7%), Retinoblastoma 231 (13.1%), Non- Hodgkins lymphoma 182 (10.3%), leukemia 158 (8.9%), brain and nervous tissue 107 (6.1%), connective tissue 105 (5.9%), bone 97 (5.5%), Hodgkins lymphoma 57 (3.2%), Non-melanoma skin 33 (1.9%). All the other remaining cancers were 233 (13.2%). Burkits lymphoma constituted only 2% of all cancers. The noted pattern of cancers in this study were compared to patterns from other countries and similarities and differences are discussed. CONCLUSION: This study showed high incidence rates of Nephroblastoma, Retinoblastoma and Kaposi sarcoma. In contrast to high income countries leukemia and brain tumours are more prevalent in older age group. Compared to other countries in Africa, Burkits lymphoma was rare. Further research is required to identify factors that influence relative frequencies in childhood cancers in Zimbabwe. Findings from this study provide baseline data for future studies. PMID- 26867249 TI - Cancer awareness and perceived barriers to health seeking in a rural population. AB - BACKGROUND: Low cancer awareness may lead to delays in cancer screening behaviour and diagnosis. OBJECTIVES: We set out to assess public awareness of cancer and perceived barriers to seeking help among the rural population of Murewa district in a cross-sectional survey of 384 conveniently selected respondents. METHODS: A self-administered and interviewer guided questionnaires were developed with the guide of the Cancer Awareness Measure (CAM) used in public awareness studies. RESULTS: Awareness of the occurrence of cancer in the population was high with 90.1% responding that they had heard about cancer. However, 60.6% of the respondents could not explain what cancer is. An association was identified between educational level and awareness on the existence of cancer in the population (p = 0.001). Age was also associated with awareness of the existence of cancer in the population (p < 0.001). Level of education was also associated with awareness on types of cancers with breast cancer (p = 0.0014), and prostate cancer (p = 0.001). Barriers to health (help) seeking included low levels of awareness of the availability of cancer screening and not being able to afford treatment services. Other barriers to help seeking included fear of screening and the costs of screening services. Unavailability of preventive and curative services for cancer at primary care level was another barrier to help seeking. CONCLUSION: There is therefore an increasing need for health promotional interventions to raise public awareness of cancer and to create supportive environments for cancer prevention, screening, early detection and treatment. PMID- 26867250 TI - Female genital schistosomiasis: pathological features and density infestation. AB - OBJECTIVES: To study the percentage distribution and Average Tissue Density (ATD) of schistosoma infestation in different parts of the Female Genital System (FGS). DESIGN: A retrospective explorative study of all surgical pathology cases examined from January to December of 2000. SETTING: Public Health Laboratories, Parirenyatwa Hospital, Harare, Zimbabwe. SUBJECTS: All archive slides cases positive for schistosoma ova were examined. INTERVENTION: To generate awareness of female genital schistosomiasis, often under diagnosed, despite causing dysmenorrhea, chronic pelvic pain, infertility, genital ulcer disease and mimicking cancer. MAIN OUTCOME MEASURES: Female genital schistosomiasis is underdiagnosed as of all forty seven (47) cases found positive microscopically, the clinicians had not raised it in their differentials. RESULTS: Forty seven (47) cases of Schistosomiasis were found with an ATD of six (6) to thirty nine (39) schistosoma ova per 10 hpf. In the lower genital tract, the cervix accounted for thirty two (68%) cases. Interestingly fifteen (47%) of cases showed association with cervical dysplasia, invasive squamous cell carcinoma or human papilloma virus koliocytosis. Presentations in the lower genital tract were of ulceration, polyps or abnormal vaginal bleeding. Surprisingly of the total forty seven (47) cases three (3%) cases were in leiomyomata. Significantly tubal ectopic pregnancy was associated with 3 (50%) cases out of six (6) cases of fallopian tube. CONCLUSION: Schistosomiasis needs more recognition as a cause of disease of the female genital tract. Its association with tubal ectopic pregnancies can be catastrophic. Further molecular studies towards its association with cervical cancer need to be done. PMID- 26867251 TI - Acute postpartum uterine inversion: a case report. AB - The case described is that of an African 24 year old and Para 2. She had a normal vaginal delivery at a local clinic and sustained an acute uterine inversion and postpartum haemorrhage. Resuscitative measures were done and she was referred to the central hospital. At the central hospital and under general anaesthesia attempts to manually replace the uterus were unsuccessful. The uterine inversion was successfully corrected at laparotomy after which an area of gangrene and perforation was noted on the uterine fundus. A decision to perform total abdominal hysterectomy was taken. The patient had an uneventful post-operative recovery. A discussion of acute postpartum uterine inversion is presented. PMID- 26867252 TI - Anaemia and iron deficiency in peri-urban school children born in a National HIV Prevention Programme in Zimbabwe: A cross-sectional study. AB - OBJECTIVE: To determine the prevalence of anaemia, iron deficiency and iron deficiency anaemia in school children who were born in a national HIV prevention programme. DESIGN: This was a community based cross-sectional study. SETTING: A resource poor peri-urban setting with high prevalence of HIV infection. SUBJECTS: School aged children six to 10 years old who were born in a national mother-to child HIV prevention programme. MAIN OUTCOME MEASURES: Haemoglobin (Hb), serum Ferritin (F) and serum Transferrin receptor (sTfR) levels. RESULTS: Three hundred and eighteen children were recruited including 21 HIV positive. The prevalence of anaemia (Hb < 11.5 grams per litre), iron deficiency (F<15 micrograms per litre) and iron deficiency anaemia (Hb < 11.5 g/L and either F < 15 MUg/L or sTfR > 8.3 MUg/L) were 15%, 4% and 2% respectively. When a higher cut-off for ferritin of 30 micrograms per litre was applied to adjust for high infection disease burden, iron deficiency prevalence increased to 32% and iron deficiency anaemia increased to 5%. Anaemia was 4.9 (C.I 1.9-12.4) times more likely to occur in HIV infected children compared to the HIV uninfected children. Maternal HIV status at birth was not related to presence of anaemia in the school children. CONCLUSION: Anaemia was of mild public health significance in this cohort of children. Iron deficiency anaemia contributed less than a quarter of the cases of anaemia. HIV infection was an important determinant for presence of anaemia. Therefore continued efforts to eliminate paediatric HIV infection as a way of reducing anaemia in children are essential. PMID- 26867253 TI - Factors influencing treatment failure in HIV positive adult patients on first line antiretroviral therapy. AB - BACKGROUND: Risk factors for treatment failure in HIV positive adults have not been studied extensively in Zimbabwe. AIM: To investigate socio-demographic, psychosocial and antiretroviral drug related factors as possible risk factors for treatment failure. OBJECTIVE: To compare the accuracy and reliability of CD4 count results in diagnosing treatment failure versus viral load results. DESIGN: A descriptive cross-sectional survey. SETTING: Harare Central Hospital adult opportunistic infections clinic. PARTICIPANTS: One hundred and eighteen (118) HIV positive participants on 1st line antiretroviral therapy (any 1 of stavudine, tenofovir or zidovudine combined with lamivudine and nevirapine or efavirenz) for at least 1 year. Participants were conveniently sampled. MAIN OUTCOME MEASURES: First line treatment failure as defined according to World Health Organisation (WHO) 2010 guidelines. RESULTS: Factors associated with higher odds of treatment failure were severe depression [OR 3.7; p-value 0.002; 95% CI 1.6-8.5] and discontinuing ART [OR 4.4; p-value 0.02; 95% CI 1.3-14.7]. Factors associated with lower odds of treatment failure were age = 42 [OR 0.3; p-value 0.007; 95% CI 0.1-0.7], taking ART on time [OR 0.2; p-value 0.02; 95% CI 0.05-0.8], time on ART > 4 years [OR 0.6; p-value 0.02; 95% CI 0.3-0.9] and female sex [OR 0.4; p-value 0.02; 95% CI 0.2-0.8]. There was statistically significant difference between CD4 count and viral load results in diagnosing treatment failure [OR 8.7; p-value 0.0005; 95% CI 3.6-21.2]. CONCLUSION: Severe depression and discontinuing ART predisposed to treatment failure. CD4 counts were not as reliable as viral load measurements in diagnosing treatment failure. PMID- 26867254 TI - The prevalence, types and effects of traditional eye medicine use among newly presenting patients at Sekuru Kaguvi Hospital Eye Unit in Harare, Zimbabwe. AB - BACKGROUND: The use of Traditional Medicines (TM) is common practice world over. Traditional Eye Medicine (TEM) use may be associated with various ocular complications including blindness. A study on the prevalence of TEM use was carried out at Sekuru Kaguvi Hospital Eye Unit (SKHEU) in Harare, with emphasis on the types ofTEM used and associated ocular complications. OBJECTIVES: To evaluate the prevalence of TEM use among newly-presenting patients at SKHEU. To identify the ocular symptoms experienced by the new clinic-attendees who had used TEM for their current eye problem. To characterize the TEM used, in terms of type, source (provider) and routes of administration. To evaluate any association between TEM use and legal blindness at presentation, destructive eye procedures and other specific ocular complications among these patients. DESIGN: Hospital based, cross-sectional analytic study. METHODS: All new patients attending one randomly selected clinic per week were recruited for the study over a period of eight months. The patients had a full clinical examination and data collected. RESULTS: The prevalence of TEM use among new patients at SKHEU was 61.5%. The initial ocular symptoms prior to the use of TEM were mainly those of ocular surface inflammation: tearing (77.4%), redness (74.9%), itchiness (71.6%) and pain (70.3%). The most common category of TEM used was plants and plant products. Most TEMs (92.4%) were administered as topical eye drops. In ninety-five percent of cases, the provider of TEM was not a formal traditional healer but rather relatives, friends and the patients self-medicated. The use of TEM was associated with specific ocular complications in 58.6% of cases. There were significant associations between use of TEM and corneal ulceration, corneal vascularisation, endophthalmitis, evisceration, exenteration and legal blindness at presentation. CONCLUSION: This study has shown that the use of TEM is common among new clinic attendees at SKHEU and is associated with specific ocular complications. PMID- 26867255 TI - Experiences of health science students during clinical placements at the University of Zimbabwe. AB - BACKGROUND: Clinical placement is an essential component of training in health sciences because it is where theory and practice interface. OBJECTIVE: To explore experiences of health sciences students during clinical placement in terms of supervision, challenges and coping strategies. DESIGN: It was a cross sectional survey. SETTING: University ofZimbabwe, College of Health Sciences. PARTICIPANTS: 179 multidisciplinary health science students. MATERIALS AND METHODS: A cross sectional survey was conducted using a self-administered questionnaire. Ethical clearance was obtained. Descriptive statistics were used for analysis. MAIN OUTCOME MEASURES: These were perceptions of students with regard to supervision, challenges faced during clinical placement and coping strategies used. RESULTS: 179 participants responded to the questionnaires. Participants enjoyed linking theory to practice. Perceptions on supervision were both positive and negative. Inadequate supervision and inappropriate behaviours by supervisors were some of the challenges faced. Almost 89% used stress-relieving strategies such as focusing on why they were doing the clinical placement and the importance of successful completion. Ninety-one per cent had never used cannabis/mbanje but 41% had engaged in sexual activity to cope with challenges. CONCLUSION: This study found that the perceptions of health sciences students about supervision clinical placement, challenges faced and the coping strategies are almost the same as those found elsewhere. It is therefore important to plan clinical placement with the involvement of clinical educators. RECOMMENDATIONS: Supervisors' workshops should be held to create a forum to discuss clinical placement issues. Follow-up of students by academics is recommended. Students should be empowered to cope with challenges. PMID- 26867256 TI - Hepatitis B and C infection at a large public sector hospital clinic: is it a burden? AB - BACKGROUND: Co-infections have become significant causes of morbidity and mortality in Human Immunodeficiency Virus (HIV) infected people. Due to shared routes of transmission, co-infection of HIV with Hepatitis B (HBV) and/or Hepatitis C (HCV) should be expected. In Zimbabwe, screening for both viruses in HIV infected people prior to treatment is not routinely practised despite the World Health Organisation (WHO) guidelines (2013) prioritising treatment where these co-infections exist. OBJECTIVE: To determine the prevalence of HBV and HCV infection in HIV infected adults at a public sector HIV clinic in Zimbabwe and to determine risk factors associated with these infections. DESIGN AND SETTING: An analytical cross-sectional survey carried out among systematically randomly sampled HIV infected patients coming for treatment between March and July 2012 at Parirenyatwa Hospital Opportunistic Infection Clinic. MATERIALS AND METHODS: Blood samples were tested for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibodies (anti-HCV). Demographic data and exposure to risk factors were collected. RESULTS: 228 antiretroviral therapy (ART) naive adults were enrolled. 7.9% (18/228) were HBsAg positive and 0.9% (2/228) were anti-HCV positive. None of the participants were infected with both viruses. CONCLUSIONS: The prevalence of HBV has not changed during this HIV era and there is no significant HCV infection in this public sector clinic which serves quite a large sector of the population that lives in Harare, Zimbabwe. Based on these results, there is no need for HCV screening but HBV screening prior to ART initiation may be required. - PMID- 26867257 TI - Prevalence of HIV among people with physical disabilities in Rwanda. AB - OBJECTIVE: To determine the prevalence of HIV among persons with physical disabilities in Rwanda. DESIGN: Across-sectional HIV diagnostic study. SETTING: A national referral rehabilitation centre in Rwanda. SUBJECTS: Persons aged 5 to 49 years with lower or upper limb impairments that were obtaining rehabilitation services at the centre. INTERVENTION: Blood samples were collected from the subjects who voluntarily accepted to participate in the study. Blood samples (4mls) were collected in vacutainer tubes and centrifuged to obtain serum which was analyzed using standard HIV rapid tests-determine HIV-1/2 Ab/Ag, SD-Bioline and UNI-Gold Recombigen HIV as a tie-breaker. MAIN OUTCOME MEASURES: The HIV status of participants--negative or positive. Descriptive statistics were computed to characterize the sample and proportions for the HIV test results. RESULTS: All one hundred and fifty-seven subjects, 59 (37.6%) male and 98 (62.4%) female, completed the study. The HIV prevalence obtained was 5.73%. All participants that tested positive were female and all tested positive for HIV-1. CONCLUSION: The prevalence obtained was higher than the population prevalence of 3.0% reported for Rwanda. Targeted HIV prevention is required for PWDs in Rwanda, with at least as much rigor as programs targeted towards the general population. Further, this should address the wide range of gender inequalities that make women particularly vulnerable to HIV. Further research needs to be conducted on a larger sample that draws participants from non-institutional settings and from other disability categories; as well as to study more specifically, the risk factors for HIV infection among PWDs in Rwanda. PMID- 26867258 TI - Work related musculoskeletal disorders among farm workers: a case study of an agricultural college in Zimbabwe. AB - INTRODUCTION: Farming is a physically laborious occupation and farm workers are at risk of developing musculoskeletal complaints. OBJECTIVE: To determine the work related musculoskeletal complaints among farm workers at an agricultural college in Zimbabwe. METHODS: A descriptive cross-sectional study was conducted using a sample size of 30 farm workers. Convenience sampling was used to select participants. Interviewer-administered questionnaires were used to assess the occupational hazards and the occurrence of musculoskeletal symptoms among farm workers. STATA version 13 was used for data analysis. Fishers' exact test was used to determine associations between agricultural activities and reported occurrence of musculoskeletal complaints. RESULTS: The lower back was the most frequently affected body site. Commonly performed activities included working prolonged periods in the same posture and working prolonged periods squatting or kneeling. There were significant associations between performing overhead activities (p = 0.029), working with the back bent (p = 0.007) and pushing or pulling heavy objects (p=0.014) with the occurrence of musculoskeletal complaints. CONCLUSION: Farm workers at Chibero College of Agriculture are exposed to a variety of occupational hazards, therefore a need for intervention to protect them from musculoskeletal complaints. Improvement in farm work practices through ergonomic training might help reduce musculoskeletal complaints. PMID- 26867259 TI - Follow the Yellow Brick Road! Update on AHNAs Strategic Plan-Focused Activities for 2015. PMID- 26867260 TI - It's About Resilience. PMID- 26867261 TI - Embracing Our Connection to Nature: Nurses as Advocates for Our Health and Food System. PMID- 26867262 TI - My Earth ... My Footprint ... My Heartvoice. PMID- 26867263 TI - Our Spaces Build Us. PMID- 26867264 TI - Holistic Nursing, Reiki, & the Centle Art of Beekeeping. PMID- 26867265 TI - LETTER to the EDITOR. PMID- 26867266 TI - Impact of praziquantel mass drug administration campaign on prevalence and intensity of Schistosoma haemamtobium among school children in Bahi district, Tanzania. AB - As part of the Tanzania National Schistosomiasis Control Programme, Bahi district in central Tanzania, received two annual rounds of praziquantel mass drug administration (MDA) to control urinary schistosomiasis in schoolchildren. The objectives of this study were to assess the impact of the two rounds of MDA on prevalence and intensity of Schistosoma haemamtobium and the impact of MDA campaigns on knowledge of urinary schistosomiasis, safe water use and contact with potentially unsafe water bodies. A quantitative cross-sectional study was carried out among schoolchildren in March and April, 2013. A structured questionnaire was used to collect information on MDA uptake, knowledge of schistosomiasis, sources of water for domestic and other uses. Urine samples were collected from each pupil to examine prevalence and intensity of S. haematobium. Transmission of schistosomiasis was assessed by sampling Bulinus spp snails for cercarial shedding. Uptake of MDA was 39.5% in 2011 and 43.6% in 2012. Prevalence of S. haematobium significantly dropped by 50.0% from 26% in 2011 to 15% in 2012 (p = 0.000). Prevalence of S. haematobium was significantly low in MDA participating (3.1%) than non-participating (28.5%) schoolchildren (p = 0.000). MDA campaigns had significant impact on knowledge of the disease (p = 0.02) and borderline impact on safe water use (p = 0.04) but had no impact on avoidance of contact with unsafe water bodies (p = 0.06). Bulinus spp. snails were found shedding schistosome cercariae indicating environmental contamination with viable S. haematobium eggs. In conclusion, though MDA significantly reduced prevalence of S. haematobium, uptake was below 50.0% and below the World Health Assembly resolution 54.19 target of 75.0% for 2010. Non-participation in MDA was the likely source of S. haematobium eggs in the environment hence the observed 15.0% prevalence of S. haematobium infection; and cercarial shedding Bulinus spp. snails indicating continuity of transmission hence the need for further health promotion campaigns. PMID- 26867267 TI - Seroprevalence of hepatitis B virus infection among antenatal clinic attendees at a tertiary hospital in Dar es Salaam, Tanzania. AB - Hepatitis B virus (HBV) infection is a serious public health problem in sub Saharan Africa. The risk of vertical transmission increases if the mother is hepatitis B surface antigen (HBsAg) positive and more so when she is also hepatitis B envelope antigen (HBeAg) positive. Since 2000, the World Health Organization recommends screening of pregnant women for HBV infection. However, this is not currently practiced in Tanzania. The objective of this study was to determine seroprevalence and associated factors of HBV infection among pregnant women attending antenatal clinic at the Muhimbili National Hospital, in Dar es Salaam, Tanzania. This cross-sectional study was conducted from August-September 2010. Data on socio-demographic characteristics, obstetric and risk factors such as history of blood transfusion, and risky sexual practices was collected. Blood samples were tested for HBsAg, HBeAg, antibodies to HBsAg (Anti-HBs), IgM antibodies to hepatitis B core antigen (Anti-HBc) and anti-HIV antibodies. A total of 310 pregnant women (28.5 +/- 5.4 years) were enrolled in the study. Thirty-one percent (96) of the women were primigravidae. Most of studied women were of low educational status and married. The seroprevalence of HBsAg was 3.9% (12/310) and none had detectable anti-HBs. None had IgM HBcAb, thus excluding acute HBV infection. All women tested negative for HBeAg. The overall seroprevalence of HIV infection was 9.7%. Three of 12 (25%) women had HBV-HIV co infection. None of the assessed associated factors were significantly related to HBV infection. In conclusion, the seroprevalence of HBsAg among women attending antenatal care at Muhimbili National Hospital is moderate. It is recommended to introduce routine antenatal screening for HBV and "at birth dose" vaccination to new born babies of mothers found to be HBsAg positive. PMID- 26867268 TI - Upper gastrointestinal endoscopic findings and prevalence of Helicobacter pylori infection among adult patients with dyspepsia in northern Tanzania. AB - Dyspepsia is a common presenting complaint of various upper gastrointestinal disorders. The symptoms of causes of dyspepsia often overlap and this makes etiological diagnosis difficult. Endoscopy is the ideal procedure for identifying organic diseases of the foregut. Helicobacter pylori infection is associated with various upper gastrointestinal pathologies. A cross-sectional study was conducted to determine endoscopic findings and H. pylori status in two hundred and eight consecutive dyspeptic adult patients between June 2009 and April 2010 at Kilimanjaro Christian medical Centre, a referral and teaching hospital in northern Tanzania. The most commonly identified endoscopic findings were gastritis (61.10%), Gastroesophageal reflux disease (GERD) (57%), and Peptic ulcer disease (PUD) (24.1%). Gastric cancer was identified in 6.7% of patients and all of them were aged 40 years and above (p = 0.00). H. pylori infection was detected in 65% (n = 130) of patients. H. pylori infection was present in 57% (n = 24) of patients who were tested within six months after eradication therapy. Gastritis and duodenal ulcer were statistically significantly associated with H. pylori (p < 0.001). No association was found between GERD and H. pylori infection (p > 0.05). Gastritis, GERD, and PUD are the leading causes of dyspepsia. H. pylori infection is present in significant proportion of dyspeptic patients. Patients with Gastritis and PUD should undergo empirical eradication therapy if a confirmatory test is not available. Patients with dyspepsia who are over 40 years of age should undergo Endoscopy (EGD) for initial work up. Study on antimicrobial susceptibility pattern of H. pylori is recommended to guide choices for evidence based treatment option. PMID- 26867269 TI - Seroprevalence of Leptospira infection in bats roosting in human settlements in Morogoro municipality in Tanzania. AB - Leptospirosis is a neglected emerging infectious disease with high burden in Africa. Major reservoirs of leptospirosis are rodents and other small mammals. Studies of leptospirosis in bats and the extent to which they contribute to its transmission to humans and domestic animals in Tanzania are lacking. The objective of this study was to determine the prevalence of leptospirosis and local Leptospira serovars in bat colonies found around human settlements in Morogoro, Tanzania. In this study, mist nets were used to capture bats at Sokoine University of Agriculture main campus, whereas bats roosting on trees at Nunge A, Nunge B and M were primary school were captured manually. Leptospirosis was determined using the gold standard microscopic agglutination test for determination of Leptospira antibodies. Six live Leptospira serovars including local Leptospira serovar Sokoine, Kenya and Lora reported in rodents and domestic animals in Tanzania, and reference serovars Hebdomadis, Canicola and Pomona were used in the study. Leptospirosis prevalence was high in bats (19.4%) and higher within colonies (27.3%). Leptospira serovar Sokoine was more prevalent (19.4%) compared to serovars Kenya (2.8%) and Lora (2.8%). Serovars Pomona, Canicola and Hebdomadis were not detected in bats. In conclusion, bats are potential reservoir and transmitter of Leptospira serovar Sokoine, hence should be prevented to access houses and roosting in human settlements to avoid public health risks. Routine diagnosis of human leptospirosis is needed in Tanzania as evidence show a high prevalence of Leptospira in reservoir hosts interacting with humans. PMID- 26867270 TI - Knowledge and perception on tuberculosis transmission in Tanzania: Multinomial logistic regression analysis of secondary data. AB - Tuberculosis (TB) is one of the most important public health problems in Tanzania and was declared as a national public health emergency in 2006. Community and individual knowledge and perceptions are critical factors in the control of the disease. The objective of this study was to analyze the knowledge and perception on the transmission of TB in Tanzania. Multinomial Logistic Regression analysis was considered in order to quantify the impact of knowledge and perception on TB. The data used was adopted as secondary data from larger national survey 2007-08 Tanzania HIV/AIDS and Malaria Indicator Survey. The findings across groups revealed that knowledge on TB transmission increased with an increase in age and level of education. People in rural areas had less knowledge regarding tuberculosis transmission compared to urban areas [OR = 0.7]. People with the access to radio [OR = 1.7] were more knowledgeable on tuberculosis transmission compared to those who did not have access to radio. People who did not have telephone [OR = 0.6] were less knowledgeable on tuberculosis route of transmission compared to those who had telephone. The findings showed that socio demographic factors such as age, education, place of residence and owning telephone or radio varied systematically with knowledge on tuberculosis transmission. PMID- 26867271 TI - Dynamic bowel obstruction: aetiology, clinical presentation, management and outcome at Bugando Medical Centre, Mwanza, Tanzania. AB - Dynamic bowel obstruction is a common and potentially dangerous surgical emergency with high morbidity and mortality worldwide. No prospective study has been done on this subject in our setting. This study was conducted to describe in our region, the aetiology, clinical presentation, management and outcome of dynamic bowel obstruction. Data were analyzed using SPSS software system. A total of 342 patients were studied. Males outnumbered females by a ratio of 2.1: 1. The median age of patients at presentation was 34 years (range 11 to 78 years). Obstructed hernias (32.7%) were the commonest cause of dynamic bowel obstruction. Abdominal pain (100%) and vomiting (86.5%) were the most frequent presenting symptoms. Thirty-one (9.1%) patients were HIV positive. Small bowel was the commonest site of obstruction accounting for 89.2% of cases. Herniorrhaphy was the most frequent surgical procedure performed in 112 (32.7%) patients. Surgical site infection (38.8%) was the most common post-operative complication and it was significantly associated with HIV positivity and low CD 4+ count (p < 0.001). The overall median of length of hospital stay was 26 days (range 1 to 72 days). Patients who had postoperative complications stayed longer in the hospital and this was statistically significant (p = 0.022). Mortality rate was 14.3%. Delayed presentation, HIV positivity, low CD 4 count (< 200 cells/MUl), high ASA class and presence of complications were the main predictors of mortality (p < 0.001). Obstructed hernias remain the commonest cause of dynamic bowel obstruction in our setting and contribute significantly to high morbidity and mortality. The majority of patients present late when the disease becomes complicated. Early diagnosis and timely definitive treatment are essential in order to decrease the morbidity and mortality associated with this disease. PMID- 26867272 TI - Postoperative pain management outcomes among adults treated at a tertiary hospital in Moshi, Tanzania. AB - Inadequately controlled postoperative pain (POP) subjects individuals to complications which may be fatal or leading to prolonged hospital stay. Complications from inadequately controlled POP may alleviate the existing shortage of hospital human resource for health in health facilities in developing countries. The burden and challenges of POP management at health facilities in Tanzania is not known. This study was therefore carried out to evaluate postoperative pain management and patient satisfaction with care given at Kilimanjaro Christian Medical Centre (KCMC). This descriptive prospective hospital based study, was conducted at the Kilimanjaro Christian Medical Centre in Moshi, Tanzania from August 2011 to March 2012. POP and patients' satisfaction with pain relief scores were assessed using pain and satisfaction numerical rating scales. Pain assessment was done at 24 hours and 48 hours after operation. Satisfaction was assessed on 48 hours post surgery. All adult patient aged 18 years and above whom were operated in general surgery ward, KCMC and accepted by signing consent were involved in the study. Patients suffering from nervous system were excluded from the study. A total number of 124 patients were recruited and participated in the study. Sixty-five (52.4%) were males and 59 (47.6%) females. Mean age (SD) years 40.9 +/- 15.4. The largest percentage of individuals had mild pain both at rest (45.2%) and during movement (44.4%). Patients whose analgesia was administered intravenously were more likely to be satisfied with POP management than those given intramuscular analgesics (P = 0.028). Analgesia used in combination increased significantly the proportion of pain free individuals 48 hours postoperative compared to 24 hours postoperative (P = 0.003). In conclusion, the postoperative pain management is still a challenge in our centre as nearly half of the patient had mild pain in.the first 48 hours post surgery. PMID- 26867273 TI - In vitro susceptibility of multi-drug resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolated from clinical specimens at Bugando Medical Centre, Tanzania to Piperacillin Tazobactam. AB - Pseudomonas spp. and Klebsiella pneumoniae are common causes of serious health care associated infections (HCAIs) worldwide. The treatment options for infections caused by multi-drug resistant (MDR) organisms are limited to tigecycline and carbapenems. A total of 172 isolates of multi-drug resistant Pseudomonas. spp and extended-spectrum beta- (ESBL) producing Klebsiella pneumoniae isolated from clinical specimens at the Bugando Medical Centre were tested for their in vitro susceptibility to piperacillin-tazobactam 100/10MUg using disc diffusion test as recommended by Clinical Laboratory Standard Institute (CLSI). Out of 59 multi-drug resistant Pseudomonas spp, 54 (92.0%) were susceptible to piperacillin-tazobactam while of 113 ESBL producing Klebsiella pneumoniae, 55 (48.7%) were susceptible to piperacillin-tazobactam 100/10MUg. Also, 20 (34.0%) of the Pseudomonas spp were both ESBL producers and susceptible to piperacillin-tazobactam 100/10MUg. A significant proportion of Pseudomonas spp isolates from clinical specimens in our setting are susceptible to piperacillin/tazobactam. This study shows that piperacillin-tazobactam offer a better option to clinicians for the treatment of health care associated infections due to Pseudomonas spp. and ESBL producing Klebsiella pneumoniae in our setting and other health facilities where these organisms are of significance. PMID- 26867274 TI - Influence of human activity patterns on epidemiology of plague in Western Usambara Mountains, Tanzania. AB - Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs to broaden its scope and formulate new hypotheses. This study was carried out to establish relationships between the nature and the spatial extent of selected human activities on one hand, and the reported plague cases on the other hand. Three outdoor activities namely, fetching water, collecting firewood and going to the market, were selected. Through enquiries the activity patterns related to these activities were mapped in 14 villages. Standard deviation ellipses represent the extent of action spaces. Over 130 activity types were identified and listed. Of these, fetching water, collecting firewood and going to the market were used for further analysis. The results indicate a significant correlation between the plague frequency and the size of these action spaces. Different characteristics of land use and related human activities were correlated with the plague frequency at village and hamlet levels. Significant relationships were found between plague frequency and specific sources of firewood and water, and specific market places. PMID- 26867275 TI - Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania. AB - Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto District. Data were collected in three landscapes differing in plague incidence. Field survey coupled with Geographic Information System (GIS) and physical sample collections were used to collect data in wet (April to June 2012) and dry (August to October 2012) seasons. Data analysis was done using GIS, one-way ANOVA and nonparametric statistical tools. The degree of spatial co-occurrence of potential disease vectors (fleas) and humans in Lushoto focus differs significantly (p <= 0.05) among the selected landscapes, and in both seasons. This trend gives a coarse indication of the possible association of the plague outbreaks and the human frequencies of contacting environments with fleas. The study suggests that plague surveillance and control programmes at landscape scale should consider the existence of plague vector contagion risk gradient from high to low incidence landscapes due to human presence and intensity of activities. PMID- 26867277 TI - Small mammal distribution and diversity in a plague endemic area in West Usambara Mountains, Tanzania. AB - Small mammals play a role in plague transmission as hosts in all plague endemic areas. Information on distribution and diversity of small mammals is therefore important for plague surveillance and control in such areas. The objective of this study was to investigate small mammals' diversity and their distribution in plague endemic area in the West Usambara Mountains in north-eastern Tanzania. Landsat images and field surveys were used to select trapping locations in different landscapes. Three landscapes with different habitats were selected for trapping of small mammals. Three types of trap were used in order to maximise the number of species captured. In total, 188 animals and thirteen species were captured in 4,905 trap nights. Praomys delectorum and Mastomys natalensis both reported as plague hosts comprised 50% of all the animals trapped. Trap success increased with altitude. Species diversity was higher in plantation forest followed by shrub, compared to other habitats, regardless of landscape type. It would therefore seem that chances of plague transmission from small mammals to humans are much higher under shrub, natural and plantation forest habitats. PMID- 26867276 TI - Predicting small mammal and flea abundance using landform and soil properties in a plague endemic area in Lushoto District, Tanzania. AB - Small mammals particularly rodents, are considered the primary natural hosts of plague. Literature suggests that plague persistence in natural foci has a root cause in soils. The objective of this study was to investigate the relationship between on the one hand landforms and associated soil properties, and on the other hand small mammals and fleas in West Usambara Mountains in Tanzania, a plague endemic area. Standard field survey methods coupled with Geographical Information System (GIS) technique were used to examine landform and soils characteristics. Soil samples were analysed in the laboratory for physico chemical properties. Small mammals were trapped on pre-established landform positions and identified to genus/species level. Fleas were removed from the trapped small mammals and counted. Exploration of landform and soil data was done using ArcGIS Toolbox functions and descriptive statistical analysis. The relationships between landforms, soils, small mammals and fleas were established by generalised linear regression model (GLM) operated in R statistics software. Results show that landforms and soils influence the abundance of small mammals and fleas and their spatial distribution. The abundance of small mammals and fleas increased with increase in elevation. Small mammal species richness also increases with elevation. A landform-soil model shows that available phosphorus, slope aspect and elevation were statistically significant predictors explaining richness and abundance of small mammals. Fleas' abundance and spatial distribution were influenced by hill-shade, available phosphorus and base saturation. The study suggests that landforms and soils have a strong influence on the richness and evenness of small mammals and their fleas' abundance hence could be used to explain plague dynamics in the area. PMID- 26867278 TI - Landform and surface attributes for prediction of rodent burrows in the Western Usambara Mountains, Tanzania. AB - Previous studies suggest that rodent burrows, a proxy for rodent population are important for predicting plague risk areas. However, studies that link landform, surface attributes and rodent burrows in the Western Usambara Mountains in Tanzania are scanty. Therefore, this study was conducted in plague endemic area of the Western Usambara Mountains in northern, Tanzania, to explore the relationship between rodent burrows, and landform and surface attributes. The study was carried out in three areas corresponding to high (Lokome), medium (Lukozi) and low.(Mwangoi) frequency of reported plague cases. Data were collected from 117, 200 and 170 observation sites for Lokome, Lukozi and Mwangoi, respectively using 100 m x 200 m quadrats. Remote sensing and field surveys were used to collect data on landform and surface attributes. Rodent burrows were surveyed and quantified by counting the number of burrows in 20m x 20m grids demarcated on the main 100m x 200m quadrats. The collected data were analysed in R software using boosted regression trees (BRT) technique. Rodent burrows were found at an elevation of above 1600m in the high and medium plague frequency landscapes. No burrows were found in the low plague frequency landscape situated below 1500m. BRT analysis shows a significant relationship between landform characteristics and rodent burrows in both high and medium plague frequency landscapes. Overall, elevation and hillshade are the most important determinants of rodent burrow distribution in the studied landscapes. It is concluded that in high altitudes, specific landform attributes (hill-shade, slope, elevation) and vegetation cover- favour rodent burrowing. PMID- 26867279 TI - Vegetation habitats and small mammals in a plague endemic area in Western Usambara Mountains, Tanzania. AB - Human plague still exists in different parts of the world, including some landscapes in north-eastern Tanzania. Wherever the hotspot of plague, small mammals seem to play a key role as host. The objective of this study was to investigate the relationship between vegetation habitats types and small mammals in a plague endemic area of Lushoto District in Tanzania. A combination of field survey and Landsat images was used to identify the vegetation habitats. Small mammals were trapped in the mapped vegetation units, and identified. In total, six main types of vegetation habitats were investigated. A total of 13 small mammal species, potentially related to plague were trapped. Results show that annual cultivated crops habitat accounted for 80% of Mastomys natalensis while natural forest accounted for 60% of Praomys delectorum. These findings have shed new light on the diversity of rodents in different habitats of natural and semi natural vegetations, and agricultural crops in the study area, which is an important intermediate step in unravelling the complex human plague system. PMID- 26867280 TI - Integrating land cover and terrain characteristics to explain plague risks in Western Usambara Mountains, Tanzania: a geospatial approach. AB - Literature suggests that higher resolution remote sensing data integrated in Geographic Information System (GIS) can provide greater possibility to refine the analysis of land cover and terrain characteristics for explanation of abundance and distribution of plague hosts and vectors and hence of health risk hazards to humans. These technologies are not widely used in East Africa for studies on diseases including plague. The objective of this study was to refine the analysis of single and combined land cover and terrain characteristics in order to gain an insight into localized plague infection risks in the West Usambara Mountains in north-eastern Tanzania. The study used a geospatial approach to assess the influence of land cover and terrain factors on the abundance and spatial distribution of plague hosts (small mammals) and plague vectors (fleas). It considered different levels of scale and resolution. Boosted Regression Tree (BRT) statistical method was used to clarify the relationships between land cover and terrain variables with small mammals and fleas. Results indicate that elevation positively influenced the presence of small mammals. The presence of fleas was clearly influenced by land management features such as miraba. Medium to high resolution remotely sensed data integrated in a GIS have been found to be quite useful in this type of analysis. These findings contribute to efforts on plague surveillance and awareness creation among communities on the probable risks associated with various landscape factors during epidemics. PMID- 26867281 TI - Land use determinants of small mammal abundance and distribution in a plague endemic area of Lushoto District, Tanzania. AB - Small mammals are considered to be involved in the transmission cycle of bubonic plague, still occurring in different parts of the world, including the Lushoto District in Tanzania. The objective of this study was to determine the relationship between land use types and practices and small mammal abundance and distribution. A field survey was used to collect data in three landscapes differing in plague incidences. Data collection was done both in the wet season (April-June 2012) and dry season (August-October 2012). Analysis of variance and Boosted Regression Trees (BRT) modelling technique were used to establish the relationship between land use and small mammal abundance and distribution. Significant variations (p <= 0.05) of small mammal abundance among land use types were identified. Plantation forest with farming, natural forest and fallow had higher populations of small mammals than the other aggregated land use types. The influence of individual land use types on small mammal abundance level showed that, in both dry and wet seasons, miraba and fallow tended to favour small mammals' habitation whereas land tillage practices had the opposite effect. In addition, during the wet season crop types such as potato and maize appeared to positively influence the distribution and abundance of small mammals which was attributed to both shelter and food availability. Based on the findings from this study it is recommended that future efforts to predict and map spatial and temporal human plague infection risk at fine scale should consider the role played by land use and associated human activities on small mammal abundance and distribution. PMID- 26867283 TI - Contribution of land use to rodent flea load distribution in the plague endemic area of Lushoto District, Tanzania. AB - Fleas associated with different rodent species are considered as the major vectors of bubonic plague, which is still rampant in different parts of the world. The objective of this study was to investigate the contribution of land use to rodent flea load distribution at fine scale in the plague endemic area of north-eastern Tanzania. Data was collected in three case areas namely, Shume, Lukozi and Mwangoi, differing in plague incidence levels. Data collection was carried out during both wet and dry seasons of 2012. Analysis of Variance and Boosted Regression Tree (BRT) statistical methods were used to clarify the relationships between fleas and specific land use characteristics. There was a significant variation (P <= 0.05) of flea indices in different land use types. Fallow and natural forest had higher flea indices whereas plantation forest mono crop and mixed annual crops had the lowest flea indices among the aggregated land use types. The influence of individual land use types on flea indices was variable with fallow having a positive effect and land tillage showing a negative effect. The results also demonstrated a seasonal effect, part of which can be attributed to different land use practices such as application of pesticides, or the presence of grass strips around fields. These findings suggest that land use factors have a major influence on rodent flea abundance which can be taken as a proxy for plague infection risk. The results further point to the need for a comprehensive package that includes land tillage and crop type considerations on one hand and the associated human activities on the other, in planning and implementation of plague control interventions. PMID- 26867282 TI - Anthropogenic soils and land use patterns in relation to small mammal and flea abundance in plague endemic area of Western Usambara Mountains, Tanzania. AB - Heterogeneity in the landscapes of West Usambara Mountains on land use and human activities has been reported. However, the interface of land use patterns and human modified soils with small mammal and flea abundance for possible explanation of plague has not been explored. This study was carried out to determine the link between anthropogenic soils and land use patterns on small mammal and flea abundance and the occurrence of reported plague in the Western Usambara Mountains in Tanzania. Standard soil survey methods were used to identify and describe soils and land use patterns on lower slopes and valley bottoms on which the surrounding villages are reported to have high and medium plague frequencies. The identified soils were characterised in terms of their morphological and physico-chemical properties and classified according to FAO World Reference Base for Soil Resources. Small mammals were trapped on the same landscape positions and identified to genus/species level. Fleas were removed from the trapped small mammals, counted and identified to species level. In total 57 small mammals were captured from which 32 fleas were collected. Results show that human settlements and mixed cultivation on lower slopes and continuous vegetable cropping in the valley bottoms are dominant land use types. Intensive use of forest soils, manuring and irrigation on farms in the studied landscapes have contributed to the development of uniquely human modified soils namely Hortic Anthrosols in the lower slopes and Plaggic Irragric Hortic Anthrosols in valley bottoms. The identified anthropogenic soils and land use patterns are associated with high abundance of small mammals (Mastomys natalensis) and flea species (Xenopsylla brasiliensis and Dinopsyllus lypusus). This phenomenon is vividly apparent in the villages with medium to high plague frequencies. The study suggests that plague surveillance programmes should consider the existing relationship between anthropogenic soils, land use patterns, small mammal and flea abundance. PMID- 26867284 TI - Prevalence of leptospirosis and toxoplasmosis: a study of rodents and shrews in cultivated and fallow land, Morogoro rural district, Tanzania. AB - Leptospirosis and toxoplasmosis are among understudied zoonotic diseases that are also not diagnosed routinely in Tanzania. Humans get leptospirosis and toxoplasmosis through contact with an environment contaminated with Leptospira bacteria and Toxoplasma protozoa from reservoir hosts, which are rodents and cats, respectively. The objective of this study was to determine the prevalence of Leptospira and Toxoplasma infections in rodents and shrews in Mikese area of Morogoro Rural District in eastern Tanzania. A total of 89 rodents and one shrew from cultivated and fallow land were tested for leptospirosis using six Leptospira serovars: Sokoine, Kenya, Canicola, Lora, Hebdomadis and Pomona. Toxoplasmosis was determined in 46 rodents brain smears. The prevalence of leptospirosis was 25.8%, and Leptospira serovar Sokoine was the most prevalent serovar (16.9%). Toxoplasma was detected in one rodent (2.17%) individual while three rodent individuals had Toxoplasma-like parasites hence were considered suspect positive. Findings suggest potential existence of human leptospirosis which needs to be further investigated. Public awareness of leptospirosis and toxoplasmosis should be promoted and their diagnosis considered in patients in health care facilities. PMID- 26867285 TI - Building the Future Environmental Health Workforce. PMID- 26867286 TI - Gender Differences in Respiratory Health of School Children Exposed to Rail Yard Generated Air Pollution: The ENRRICH Study. AB - Studies about environmental burdens often explore overall community risk. Increasing evidence suggests, however, differential burdens by gender and age. The purpose of the authors' research was to determine if gender-related difference exists among children in a region plagued with poor air quality and if increased exposure to pollutants from a major goods movement rail yard influences the relationship. Using a cross-sectional study design, the authors provided respiratory screening for children at two elementary schools. Compared to females, males were at significantly greater odds of exhibiting elevated fractional exhaled nitric oxide (FeNO) but less likely to exhibit reduced lung volume. Even in an area of overall poor air quality, the authors found that male children were a vulnerable subpopulation for greater elevated FeNO, while females were at increased risk for reduced lung capacity. Understanding differential burdens in vulnerable subpopulations is critical to providing timely and responsive strategies targeted towards health-based prevention and intervention activities. PMID- 26867287 TI - A Step Towards Improving Food Safety in India: Determining Baseline Knowledge and Behaviors Among Restaurant Food Handlers in Chennai. AB - With the establishment of the Food Safety and Standards Authority of India (FSSAI) and new food safety regulations, a precedent has been set to prevent foodborne illness in India. The objective of the authors' study was to identify knowledge gaps among food handlers in Chennai, Tamil Nadu, to establish priorities for future intervention. A 44-question survey was administered to 156 food handlers at 36 restaurants in Chennai between April and June of 2011. The overall mean knowledge score was 49% and knowledge gaps related to hand hygiene, proper food cooking and holding temperatures, and cross contamination were identified. Food handlers with a Medical Fitness Certificate scored significantly higher than those without a certificate, after controlling for food safety training and level of education (p < .05). As the FSSAI standards now require a medical certificate for restaurant licensure and registration, consideration should be given to include an educational component to this certification with an explanation of expected food safety behavior. PMID- 26867288 TI - Safety Evaluation of Metal Exposure From Commonly Used Hair Dyes and Tattoo Inks in Nigeria. AB - In the study described in this article, the concentrations of metals (cadmium, copper, chromium, aluminum, lead, nickel, zinc, cobalt, manganese, and iron) in samples of some commonly used hair dyes and tattoo inks were determined with a view to providing information on the hazards associated with the use of these products. The concentrations of metals were measured after nitric acid/perchloric acid/hydrogen peroxide digestion by atomic absorption spectrometry. Results indicated that the tattoo ink samples contained allergenic metals such as nickel, chromium, and cobalt at concentrations above the suggested limit of 1 MUg/g for greater skin protection, and the toxic metals were below their respective prescribed limits, as impurities in ingredients for use for cosmetics, in the majority of the samples. PMID- 26867289 TI - Knowledge and Food Handling Practices of Nurses in a Tertiary Health Care Hospital in Nigeria. AB - Food safety in hospitals is important to protect patients whose immunity may be compromised by their illness. The safety of food served to patients is dependent on its handling acquisition of raw food items, to preparation, packaging, and distribution. The study described in this article assessed the knowledge and food handling practices of nurses in the food chain to patients in the hospital wards. The mean age of respondents was 33.7 +/- 9.3 years and 180 (56.6%) had worked in the hospital for 1-5 years. While respondents had good knowledge scores overall, only 22 (6.5%) knew the correct temperature for maintaining hot, ready-to-eat food. Also, 332 (97.6%) respondents knew the importance of hand washing before handling food while 279 (84.1%) always wash hands before handling food. The study revealed a decline in performance over time, from knowledge and attitudes to practice in food handling. Therefore, regular training on safe food handling procedures should be mainstreamed into the training curriculum of staff nurses in health care institutions. PMID- 26867290 TI - Assessment of the Physicochemical Quality of Drinking Water Resources in the Central Part of Iran. AB - The aim of the study described in this article was to assess the physicochemical quality of water resources in Isfahan province, located in the central part of Iran, from June to November 2012. Comparison of the results with the acceptable limits recommended by the World Health Organization (WHO) for drinking water showed that nitrate, chloride, iron, and fluoride concentrations exceeded the maximum acceptable level in 12.3%, 9.2%, 6.8%, and 1.5% of samples, respectively. Total dissolved solids (TDS) and turbidity values also exceeded the maximum acceptable level in 9.2% and 3.1% of samples, respectively. In general, the quality of drinking water resources in the central part of Iran at present is mostly acceptable and satisfactory. It may be deteriorated in the future, however, because water quantity and quality in arid and semiarid areas are highly variable over time. Therefore, continued monitoring of the water resources quality is extremely important to environmental safety. PMID- 26867291 TI - Seat Belt Usage Interventions for Motor Vehicle Crash Prevention on the Pine Ridge Indian Reservation, South Dakota. AB - Motor vehicle crashes (MVC) are the leading cause of death from severe injuries on the Pine Ridge Indian Reservation (PRIR), averaging 16 MVC deaths per year from 2002 to 2011. The Sacred Cargo Coalition was established in PRIR in 2007 to implement intervention strategies to increase seat belt usage and reduce MVC fatalities, including seat belt law enforcement, creating a traffic court system, and educational campaigns on MVC prevention. The study described in this article examined the effectiveness of the interventions on increasing the seat belt usage rates and reducing MVC deaths. Secondary data were collected from the National Highway Traffic Safety Administration and other federal and local agencies. Seat belt usage rates increased an average of 6.8 percentage points from 2007 (10%) to 2012 (44%). MVC fatalities decreased by 46.7% from the preintervention to the intervention period. Maintenance and improvement of the intervention strategies may be achieved by seeking additional funding and including appropriate engineering activities in PRIR. PMID- 26867292 TI - An Expanding and Shifting Focus in Recent Environmental Health Literature: A Quantitative Bibliometric Study. AB - This special report characterizes the patterns of environmental health literature from 1993 to 2012 by using bibliometric techniques based on databases of the Science Citation Index and the Social Science Citation Index. "Research article" was the most widely used document type, accounting for 71.7% of the total records (5,053), and 94.9% of these articles were published in English. The number of environmental health publications is growing along with an increasing level of communication. The U.S. was the largest contributing country with the highest h index (85) and the most publications (1,854), followed by the UK and Canada. Environmental Health Perspectives and the Journal of Environmental Health were the top two most productive journals. The most cited article in each main research area is also listed. The authors' study not only identifies global characteristics in environmental health research, but also influences researchers' selection of future studies and publications. PMID- 26867293 TI - Pesticide Exposure in the Caribbean: A Case From Nutmeg Processing. AB - Many developed countries around the world have implemented regulations to phase out or greatly restrict the use of pesticides. Pesticides are still utilized with minimal restrictions, however, in fumigating agricultural commodities in developing countries such as Grenada. This special report presents the case of a nutmeg factory worker in Grenada who worked with various pesticides including methyl bromide, magnesium phosphide (magtoxin), and aluminum phosphide (phostoxin) without the proper awareness and utilization of health and safety measures. The nutmeg factory worker later developed metastatic bladder cancer, which may have been triggered by a combination of individual risk factors along with long-term occupational exposure to these pesticides. In this special report, the occupational health importance of prevention in a work environment with significant exposure to pesticides is highlighted as well as some of the fundamental deficiencies in awareness among workers in developing nations concerning the deleterious effects of frequent exposure to pesticides. PMID- 26867294 TI - Association Between Low Temperature During Winter Season and Hospitalizations for Ischemic Heart Diseases in New York State. AB - Most prior research investigating the health effects of extreme cold has been limited to temperature alone. Only a few studies have assessed population vulnerability and compared various weather indicators. The study described in this article intended to evaluate the effects of cold weather on hospital admissions due to ischemic heart disease, especially acute myocardial infarction (AMI), and to examine the potential interactive effects between weather factors and demographics on AMI. The authors found that extremely low universal apparent temperature in winter was associated with increased risk of AMI, especially during lag4-lag6. Certain demographic groups such as the elderly, males, people with Medicaid insurance, people living in warmer areas, and areas with high PM2.5 concentration showed higher vulnerabilities to cold-AMI effects than other groups. PMID- 26867295 TI - Measurements of Arsenic in the Urine and Nails of Individuals Exposed to Low Concentrations of Arsenic in Drinking Water From Private Wells in a Rural Region of Quebec, Canada. AB - Chronic exposure to inorganic arsenic leads to an increased risk of cancer. A biological measurement was conducted in 153 private well owners and their families consuming water contaminated by inorganic arsenic at concentrations that straddle 10 MUg/L. The relationship between the external dose indicators (concentration of inorganic arsenic in wells and daily well water inorganic arsenic intake) and the internal doses (urinary arsenic--sum of As(III), DMA, and MMA, adjusted for creatinine--and total arsenic in toenails) was evaluated using multiple linear regressions, controlling for age, gender, dietary sources of arsenic, and number of cigarettes smoked. It showed that urinary arsenic was associated with concentration of inorganic arsenic in wells (p < .001) and daily well water inorganic arsenic intake (p < .001) in adults, and with daily well water inorganic arsenic intake (p = .017) and rice consumption (p = .022) in children (n = 43). The authors' study reinforces the drinking-water quality guidelines for inorganic arsenic. PMID- 26867296 TI - Health Risk Assessment Research on Heavy Metals Ingestion Through Groundwater Drinking Pathway for the Residents in Baotou, China. AB - Drinking groundwater is a significant pathway for human exposure to heavy metals. To evaluate the health effect of some heavy metals ingestion through the groundwater drinking pathway, the authors collected 35 groundwater samples from the drinking water wells of local residents and the exploitation wells of waterworks in Baotou, China. The monitoring results indicate that the groundwater had been polluted by heavy metals in some regions of the study area. A health risk assessment model derived from the U.S. Environmental Protection Agency was used to determine the noncarcinogenic and carcinogenic effects to residents who drink groundwater. All the respondents in the study area were at potential risk of carcinogenic health effects from arsenic when using the lowest safe standard for carcinogenic risk (1E-06). The hazard quotient values for noncarcinogenic health risk of arsenic exceeded 1 in 14.3% of the sampling wells in the study area. The research results could provide baseline data for groundwater utilization and supervision in the Baotou plain area. PMID- 26867297 TI - The Impact of Extremes in Outdoor Temperature and Sunshine Exposure on Birth Weight. AB - Following the "fetal origins of adult disease" hypothesis, environmental determinants of birth weight regained interest. The authors applied a detailed spatial-time exposure model for climatological factors thought to affect fetal growth: seasonality, temperature, and sunshine. Daily climatological data (29 stations) were linked to 1,460,401 term births with an individual exposure matrix for each pregnancy. Linear regression was utilized to determine effects of climatological factors on individual birth weight and existing spatial variations in birth weight. In The Netherlands substantial regional climatological differences exist. Summer was associated with significantly reduced birth weight (16-19 g). Minimum and maximum temperatures were significantly associated with increased and reduced birth weight, respectively. Spatial birth weight differences ranged from -11 to +25 g, with lowest birth weights in inland areas. The authors demonstrate birth weight to be associated with climatological factors; negative birth weight effects of maximum temperature exposure confirm results from animal studies. Consequently, a climate footprint is visible in the spatial birth weight differences. PMID- 26867298 TI - Radon Risk Communication Strategies: A Regional Story. AB - Risk communication on the health effects of radon encounters many challenges and requires a variety of risk communication strategies and approaches. The concern over radon exposure and its health effects may vary according to people's level of knowledge and receptivity. Homeowners in radon-prone areas are usually more informed and have greater concern over those not living in radon-prone areas. The latter group is often found to be resistant to testing. In British Columbia as well as many other parts of the country, some homes have been lying outside of the radon-prone areas have radon levels above the Canadian guideline, which is the reason Health Canada recommends that all homes should be tested. Over the last five years, the Environment Health Program (EHP) of Health Canada in the British Columbia region has been using a variety of different approaches in their radon risk communications through social media, workshops, webinars, public forums, poster contests, radon distribution maps, public inquiries, tradeshows and conference events, and partnership with different jurisdictions and nongovernmental organizations. The valuable lessons learned from these approaches are discussed in this special report. PMID- 26867300 TI - Parks: An Opportunity to Leverage Environmental Health. PMID- 26867299 TI - Civic Engagement Builds Capacity for Health Departments. PMID- 26867301 TI - (Work) Force = Mass x Acceleration. PMID- 26867302 TI - [How I TREAT ... THE ROLE OF DPP-4 INHIBITORS (GLIPTINS) IN THE TREATMENT OF TYPE 2 DIABETES]. AB - Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are more and more prominent medications in the management of type 2 diabetes (T2D), with five molecules commercialized and as many fixed-dose combinations with metformin. After failure of metformin monotherapy, gliptins compete with old medications such as sulphonylureas, on the one hand, or with new oral antidiabetic agents such as inhibitors of renal sodium-glucose cotransporters type 2 (SGLT2) (gliflozines), on the other hand. Another alternative is the use of an incretin mimetic (agonist of glucagon-like peptide-1 receptors, to be injected subcutaneously) rather than an incretin enhancer such as a gliptin, before considering insulin therapy. This article analyses the arguments in favour of DPP-4 inhibitors. We will mainly consider the use of gliptins in patients with recently diagnosed T2D, in elderly and frail patients and in those with chronic kidney disease. To illustrate the discussion, we will analyze the results of both interventional and observational studies with vildagliptin. Obviously, these various groups of patients represent a large proportion of T2D population. PMID- 26867303 TI - [MAZABRAUD SYNDROME: A CASE REPORT]. AB - We report a case of Mazabraud syndrome diagnosed in a 53 year old female patient. This disease is characterized by the association of a fibrous dysplasia with one or several intramuscular myxoma(s). The literature related to this pathology is poor and only reports a few cases. The aetiology has not been fully established: a genetic hypothesis seems most likely given the common association with McCune Albright syndrome. Although rare, the incidence of Mazabraud syndrome seems underestimated, probably out of ignorance. The aim of this article is to describe Mazabraud syndrome and its common features. The management of fibrous dysplasia of bone and benign soft tissue tumors will also be outlined. PMID- 26867304 TI - [Moxifloxacin and iris transillumination]. AB - Bilateral Acute Iris Transillumination (BAIT) is a new clinical entity characterized by acute onset of pigment dispersion in the anterior chamber and angle, depigmentation of the iris stroma and permanent iris transillumination, mas- querading as uveitis. An association with oral moxifloxacin is reported in some articles. We describe one case of bilate- ral acute iris transillumination, following the use of systemic moxifloxacin. PMID- 26867305 TI - [ENDOSCOPIC LUNG VOLUME REDUCTION IN PULMONARY EMPHYSEMA]. AB - Emphysema is characterized by an irreversible alveolar destruction, a progressive lung hyperinflation and a dysfunction of respiratory muscles. It induces a respiratory functional limitation and a decrease of quality of life. Endoscopic lung volume reduction represents a potential alternative to surgical treatments for advanced heterogeneous emphysema without concomitant surgical morbidity. The different bronchoscopic systems for lung volume reduction currently under evaluation are presented. PMID- 26867306 TI - [CUTANEOUS INFECTIONS ASSOCIATED WITH HEMATOLOGICAL MALIGNANCIES]. AB - Patients suffering from a malignant hemopathy represent a population at high risk for cutaneous infections that are potentially severe. Viral, bacterial and mycotic infections of the skin are not rare. Their semiology possibly appears falsely reassuring. Some skin lesions are primary events. Other lesions are secondary following contiguous extension of another deeper location, or represent a sign of septicemia. Taking care of the patient must be precocious and rigorous. PMID- 26867307 TI - [MANAGEMENT OF THYMIC EPITHELIAL TUMORS]. AB - Thymic epithelial tumors (TET) are rare. Their optimal care is still poorly defined because of their rarity and of the resulting difficulty to conceive large clinical trials. This review of the literature presents the current clinical and therapeutic data on this form of tumors and underlines the need for a multidisciplinary approach to advanced stage TET. Three clinical situations can be encountered: encapsuled tumors lead to radical surgery; tumors associated with capsular invasion justify a postoperative radiotherapy; advanced stages require a multimodal treatment by chemotherapy, possibly completed by surgery and adjuvant radiotherapy. Besides systemic chemotherapies, the place of new therapeutic strategies, such as somatostatin analogues and targeted treatments, requires to be defined. Treatment of late stage TET is based upon a multidisciplinary dialogue, ideally by a reference team. PMID- 26867308 TI - [CA, P, AND MG POSTNATAL METABOLISM AND REQUIREMENTS IN PARENTERAL AND ENTERAL NUTRITION OF PREMATURE INFANTS]. AB - During the last trimester of gestation, transplacental mineral transfer and fetal mineral accretion is particularly high: 2.3-3.2 mmol/kg/day (90-130 mg/kg/d) of calcium, 2.4-2.7 mmol/kg/d (65-75 mg/kg/day) of phosphorus and 0.12-0.20 mmol/kg/d (2.9-4.8 mg/kg/day) of magnesium. After birth, there is a dramatic change in bone mineral metabolism from a maximal bone deposition during fetal life to a postnatal bone turnover stimulation improving bone structure and resistance. This physiological change could partly reduce the mineral requirements, as minerals available from the remodeling activities could be recycled for bone mineralization. In addition, recent studies in preterm infants, suggest that the use of early more "aggressive" nutritional support, providing high aminoacid intakes from the first day of life, may induce a "refeeding like syndrome" suggesting that early phosphorus and electrolytes supplies are also necessary. The aim of the present paper is to review the mineral metabolism of Very Low Birth Weight (VLBW) infants during the first weeks of life at the light of the more recent studies and to revise the nutritional recommendations for mineral parenteral and enteral intakes in VLBW infants. PMID- 26867309 TI - [CONTROVERSIES REGARDING THE ACCURACY AND LIMITATIONS OF FROZEN SECTION IN THYROID PATHOLOGY: AN EVIDENCE-BASED ASSESSMENT]. AB - Palpable thyroid nodules are present clinically in 4-7% of the population and their prevalence increases to 50%-67% when using high-resolution neck ultrasonography. By contrast, thyroid carcinoma (TC) represents only 5-20% of these nodules, which underlines the need for an appropriate approach to avoid unnecessary surgery. Frozen section (PS) has been used for more than 40 years in thyroid surgery to establish the diagnosis of malignancy. However, a controversy persists regarding the accuracy of FS and its place in thyroid pathology has changed with the emergence of fine-needle aspiration (FNA). A PubMed Medline and SpringerLink search was made covering the period from January 2000 to June 2012 to assess the accuracy of ES, its limitations and indications for the diagnosis of thyroid nodules. Twenty publications encompassing 8.567 subjects were included in our study. The average value of TC among thyroid nodules in analyzed studies was 15.5 %. ES ability to detect cancer expressed by its sensitivity (Ss) was 67.5 %. More than two thirds of the authors considered PS useful exclusively in the presence of doubtful ENA and for guiding the surgical extension in cases confirmed as malignant by FNA; however, only 33% accepted FS as a routine examination for the management of thyroid nodules. The influence of FS on surgical reintervention rate in nodular thyroid pathology was considered to be negligible by most studies, whereas 31 % of the authors thought that FS has a favorable benefit by decreasing the number of surgical re-interventions. In conclusion, the role of FS in thyroid pathology evolved from a mandatory component for thyroid surgery to an optional examination after a pre-operative FNA cytology. The accuracy of FS seems to provide no sufficient additional benefit and most experts support its use only in the presence of equivocal or suspicious cytological features, for guiding the surgical extension in cases confirmed as malignant by FNA and for the identification of other potentially confusing intraoperative findings. PMID- 26867310 TI - [FROM THE LAW "RELATED TO ABNORMAL AND HABITUAL OFFENDERS" TO THE LAW OF INTERNMENT OF PERSONS WITH MENTAL DISORDERS"]. AB - The Belgian forensic system for offenders with mental disorders is organized according to a principle of social defense. It is characterized, on the one hand, by the protection of the society and neutralization of risks and, on the other hand, by the requirements of mental care for the internee. The evolution of the legal framework from the 1930 law related to "abnormal and habitual offenders" to the law about "internment of persons with mental disorder" voted in 2014 reflects the vicissitudes born of the tension between these two pillars. In this difficult balance between medical and judicial issues, although published, but not yet effective, the 2014 version of the law is, in many ways, a positive development in the integration of internees and their needs. PMID- 26867311 TI - [Construction of Recombinant Adenovirus Vector with Human/Mouse Interferon Gene and Its Transfection into Human Umbilical Cord Mesenchymal Stem Cells]. AB - OBJECTIVE: Construction and identification of recombinant adenovirus vector with human/mouse interferon (IFN-gamma) and effectively transfection into human umbilical cord mesenchymal stem cells (HUMSCs). METHODS: IFN-gamma gene of human/mouse were amplified from the plasmid by polymerase chain reaction (PCR) and then inserted into the plasmid pDC316 to generate pDC316-IFN-gamma. After being confirmed by restriction enzyme digestion and DNA sequencing, the DNA encoding IFN-gamma in the new structure were inserted into the vector of recombinant plasmid adenovirus and confirmed by restricition enzyme digestion. Then the human embryonic kidney cell line 293 were transfected with confirmed Ad IFN-gamma, and the recombinant adenovirus were amplified, and the virus titer were detected using 50% tissue culture infective dose (TCID50) assay. The expression of the green fluorescent protein (GFP) and IFN-gamma were detected by fluorescent microsope and Western blot and ELISA after the recombinant adenovirus transfected HUMSCs. RESULTS: The recombinant adenovirus Ad-hIFN-gamma were constructed successfully, and amplified with titer of 1.6 x 10(10) IU/mL. The titer of Ad-mIFN-gamma was 1.0 x 10(10) IU/mL and the titer of Ad-GFP was 1.0 x 10(9) IU/mL. The green fluorescence proteins could be observed under fluorescent microscope in HUMSCs 24 h after transfection and with a stronger degree after 72 h, and IFN-gamma expression in HUMSCs were confirmed by Western blot and ELISA. CONCLUSION: Construction and identification of recombinant adenovirus vector of human/mouse IFN-ygamma and effectively transfection of HUMSCs were successful. PMID- 26867312 TI - [Estrogen Receptor Subtype-mediated Luciferase Reporter Gene Assays for Determining (anti) Estrogen Effect of Chemicals]. AB - OBJECTIVE: To establish gene assays for determining (anti) estrogen effect of environmental chemicals; and to compare the reactivity and sensitivity of two assays with different estrogen subtype. METHODS: Human estrogen receptor a (hERalpha) and hERbeta mediated reporter gene assays employing firefly luciferase (Luc) were developed. The expression plasmid hERalpha or hERbeta was constructed and transiently co-transfected into LLC-MK2 cells with pERE-minP-Luc2P reporter plasmid and the control plasmid pGL4.74. Estradiol (E2) and diethylstilbestrol (DES) served as positive test substances to verify the performance of the assays. The effectiveness of the assays for detecting anti-estrogenic activity was tested using 10(-5) mol/L ICI 182, 780 under different concentrations of E2. The performance of the two subtype-mediated assays was verified and compared using bisphenol A (BPA) and genistein (GS). RESULTS: The hERalpha mediated assay found expression of reported gene at 1.9 x 10(-11) mol/L E2; and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 30.7-fold of vehicle control. The hERbeta mediated assay found expression of reporter gene at 2.2 x 10(11) mol/L E2, and the largest luciferase activity was shown at 10(-8) mol/L E2, resulting in 14.4-fold of vehicle control. ICI 182, 780 inhibited estrogenic activity of E2 significantly. In both assays, E2 failed to induce luciferase activity without hER-pcDNA3.1. BPA and GS induced luciferase activity. CONCLUSION: Both assays have high sensitivity and reproducibility for detecting (anti) estrogen effect. The pGL4-based hERbeta has lower sensitivity than the hERalpha- mediated reporter gene assay. BPA shows stronger estrogenic activity than GS in hERalpha mediated reporter gene assay; whereas, GS shows stronger estrogenic activity than BPA in hERbeta mediated reporter gene assay. PMID- 26867313 TI - [Bactericidal Activity of Constructed Recombinant Fusion Protein Pheromonicin CT]. AB - OBJECTIVE: To construct engineering peptide pheromonicin-Clostrzaum tretant krn ui), and to test its bactericidal activity. METHODS: We amplified the gene of variable regions from hybridoma cells which secreted monoclonal antibody (mAb) against antigen in the membrane of Clostridium tetani and linked the small antibody mimetic to the channel-forming domain of colicin Ia to create Ph-CT. The Ph-CT was purified by CM sepharose ion-exchange column. Its in vitro antibacterial activity was evaluated by colony culture with different doses of Ph CT (final concentration 2, 4, 8, and 16 microg/mL,respectively). Then we inoculated culture medium with CT strains and different doses of Ph-CT (final concentration of 4 and 16 microg/mL). The in vivo antibacterial activity of Ph-CT was evaluated by cumulative survival of mice. After 16 hours' anaerobic culture, the mice was treated with filtered CT medium or CT medium. RESULTS: We constructed Ph-CT successfully. CT colonies appeared in the CT medium treated with Ph-CT (2, 4 microg/mL), while no colony appeared in the CT medium treated with Ph-CT (8, 16 microg/mL). All mice survived when they were injected with filtered CT medium treated with Ph-CT (4, 16 microg/mL) and CT medium treated with Ph-CT (16 microg/mL). Three (50%) mice survived when they were injected with CT medium treated with Ph-CT (4 microg/mL). All mice in the control groups died after CT infections. CONCLUSION: Ph-CT may be of value as antibiotics against Clostridium tetani. PMID- 26867314 TI - [The Effects of Thymosin alpha1 on Immune Function of Mice after Skin Transplantation]. AB - OBJECTIVE: By establishing C57-BABL/c mice allogeneic skin transplantation model, to analyze the immune system function with the administration of thymosin al (Tal) in mouse after skin transplantation; and to explore the mechanism of specific immune tolerance induced by Tal in vivo. METHODS: 80 C57 mice and 80 BABL/c mice were used as donor and acceptor respectively to establish C57-BABL/c mice allogeneic skin transplantation model and divided into four groups: Group A, control group (without any treatment, n=20); Group B, CsA treatment group (CsA 10 mg/kg, n=20); Group C, Tal treatment group (Tal 400 microg/kg, n=20) and Group D, combination therapy group (CsA 10 mg/kg & Talphal 400 microg/kg, n=20). In the three experimental group, the drug of each group were respectively administrated by intraperitoneal injection daily, for 21 d. The survival of skin graft were observed and recorded, the Luminexx MAP for cytokine detection were performed in 1, 7, 14, 21 d after treatment, skin grafts were taking for HE staining, and flow cytometry were performed for lymphocyte phenotype. RESULTS: After transplantation, in 1, 7, 14, 21 d, the cytokine of Group B, C and ID compared to Group A, as well as Group D to B&C respectively, shows a decreaing of IL-1, IL-2, IL-6, IL-17 value and increasing of IL-10 significantly (P<0.05) at the same time point; While no statistical significance shows between Group B and C. Compared with other groups, Group D have a high ratio of CD4/CD8, and a high percentage of CD4+ CD25+ T cells (P<0.05). CONCLUSION: Administrated Tal after transplantation, can decrease the graft damage from T cells, but could not prevent rejection. PMID- 26867315 TI - [Effect of Berberine on the Insulin Resistance and TLR4/IKKbeta/NF-kappaB Signaling Pathways in Skeletal Muscle of Obese Rats with Insulin Resistance]. AB - OBJECTIVE: To explore the possible mechanism of berberine improve insulin resistance in skeletal muscle of obese rats. METHODS: Forty Wistar rats were divided into normal control group (NC group, n =10) and high fat food group (HF group, n=30). After the obese model rats established successfully, the rats of NC group (n=10) and HF group (n=10) were sacrificed. The level of fasting plasma endotoxin (ET) was detected. The expression of Toll-like receptor 4 (TLR4) mRNA in skeletal muscle were detected by real time quantitative PCR. The expression of TLR4, IkappaB kinase beta (IKKbeta), phospho-IKKbeta(Ser181) (p-IKKbeta(Ser181)), nuclear factor-kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phospho-IRS 1(Ser307) (p-IRS-1(ser307)) and the tyrosine phosphorylation of IR and IRS-1 (p IR(Tyr) and p-IRS-1(Tyr)) protein in skeletal muscle were detected by Western blot. The twenty HF group rats were randomly divided into two group: the fat model control group (FC group, n=10) were fed with high fat diet and distilled water. The fat berberine group (FB group, n=10) were fed with high fat diet and berberine. All rats were sacrificed after effective interventions of eight weeks. The same indexes as the first part of experiment were detected. Results The results showed that the level of ET was increased. The TLR4/IKKneta/NF-kappaB signaling pathway is activated and the expression of TNF-alpha was increased of the skeletal muscle in obese rats. However, the insulin signaling pathways of the skeletal muscle in obese rats was inhibited. Berberine could reduce the level of ET of obese rats, down-regulate the TLR4/IKKbeta/NF- kappaB inflammation signaling pathway and improve insulin resistance of skeletal muscle in obese rats. CONCLUSION: Our study revealed that berberine could reduce the level of ET of obese rats, down-regulate the TLR4/IKKbeta/NF-kappaB inflammation signaling pathway in skeletal muscle and berberine can improve insulin resistance of skeletal muscle through inhibiting the active of the TLR4/IKKbeta/NF-kappaB signaling pathway. PMID- 26867316 TI - [Umbilical Cord-derived Mesenchymal Stem Cells Grafts for Neonatal Rats Model of HIBD: the Mechanism of PI3K/Akt Signaling Pathway]. AB - OBJECTIVE: To investigate the role of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway for umbilical cord-derived mesenchymal stem cells (UC-MSCs) treating in neonatal rats with hypoxia-ischemia brain damage (HIBD). METHODS: P10 SD rats were divided into sham group, MSCs group, inhibitor (LY 294002) group (LY group) and HIBD group randomly. To establish a neonatal rat model of HIBD, UC-MSCs labeled with Brd U were transplanted into the lateral ventricle of rats. At 24 and 48 h after transplantation, the number of apoptotic cells was detected by TUNEL, while the expression of caspase3 protein and phosphorylation of Akt (P-Akt) were quantified by Western blot. RESULTS: At 24 and 48 h after transplantation, both the apoptotic cells and caspase3 protein expression in MSCs group were less than those in LY group and HIBD group (P<0. 05), while the expression of P-Akt was higher than those in LY group and HIBD group (P<0.05), and with the passage of time after transplantation, the expression of each index showed a downward trend. CONCLUSION: The apoptotic cells of brain and the expression of caspase3 protein decrease, while the expression of P-Akt increase. PI3K/Akt signaling pathway may be an important mechanism for UC MSCs transplantation in HIBD rats. PMID- 26867317 TI - [Physicochemical Property of iRGD Peptide Modified Doxorubicin Loaded Liposome and Its Effect on Cancer Cell Growth]. AB - OBJECTIVE: To determine the physicochemical properties of iRGD conjugated doxorubicin loaded liposome (iRGD-LP-DOX), and its effect on targeting and inhibiting growth of A549 cells. METHODS: Liposomes were observed under a transmission electron microscope. Release of doxorubicin from iRGD-LP-DOX was detected by the dialysis bag method. The efficiency of cellular uptake and tumor spheroids penetration on A549 cells in vitro was determined. The anti proliferation efficiency of iRGD-LP-DOX was evaluated by MTT assay using IC50 (50% inhibition concentration). RESULTS: iRGD-LP-DOX was spherical in a uniform size. Free DOX was released by 100% in 5 h, while LP-DOX and iRGD-LP-DOX were released by about 40% in 48 h. A higher level of iRGD-LP-DOX uptaken by A549 was found compared with that of LP-DOX (P<0.01). Higher fluorescence intensity was detected with iRGD-LP-DOX than with LP-DOX in tumor spheroid. The MTT assay confirmed strong inhibitory effect of iRGD-LP-DOX (P<0.01). CONCLUSION: iRGD can enhance uptake of liposomes by A549 cells and inhibit the proliferation of tumor cells. PMID- 26867318 TI - [The Protective Effect of B7-H4 on Concanavalin A Induced Hepatic Injury in Mice]. AB - OBJECTIVE: To explore the protective effect and its mechanism of B7-H4 on the immuno hepatic injury. METHODS: The immuno hepatic injury was induced by Concanavalin A (Con A). Sixty KM mice were randomly divided into 4 groups with 15 mice in each group: Group A (saline), Group B (pcDNA3.1-mB7-H4-Fc), Group C (pcDNA3.1), Group D (Con A). One day before the injection of Con A (25 mg/kg), the mice in Group B and Group C received the injection of 100 pg pcDNA3.1-mB7-H4 Fc and 100 microg pcDNA3.1 respectively. The blood samples were collected at 12 h, 24 h and 48 h after Con A injection, the levels of ALT, AST, IL-4 and IFN gamma were measured. Five mice in each group were sacrificed at the above 3 time points, the liver tissue were harvested for histopathological detection. RESULTS: After Con A injection, the level of ALT in Group B, C, and D were higher than that in Group A. The level of ALT in Group B was lower than that in Group C and D. The significant difference was found between Group B and Group C. The hepatic injury of Group B was less serious than that of Group C and D. CONCLUSION: B7-H4 may have protection on the immune injury of liver induced by Con A. PMID- 26867319 TI - [Expression Difference of MicroRNAs in Colorectal Adenoma and Colorectal Cancer]. AB - OBJECTIVE: To investigate the expression difference of microRNAs in colorectal tubular adenoma, tubulovillous adenoma and colorectal cancer. METHODS: Real time polymerase chain reaction was used to analysis the expression level of miR-1, miR 9, miR-31, miR-135a, miR-137 and miR-145 between colorectal tubular adenoma (n=44), tubulovillous adenoma (n=16), colorectal cancer (n=20) and paired paracancerous normal colorectal tissues. RESULTS: Compared with paired paracancerous normal colorectal tissues, colorectal tubular adenoma had decreased expression of miR-1, miR-9, miR-137 and miR-145 as well as increased expression of miR-31 and miR-135a. Colorectal tubulovillous adenoma had decreased levels of miR-1, miR-137, miR-145, as well as increased levels of miR-9, miR-135a, and miR 31. Colorectal cancer had the expressions of miR-1, miR-9, miR-137 and miR-145 decreased while the expression of miR-135a and miR-31 increased. CONCLUSION: The differential expressions of microRNAs suggested that miRNAs participate in the development of colorectal adenoma and cancer. PMID- 26867320 TI - [Oxidative Stress Level of Vanadium-exposed Workers]. AB - OBJECTIVE: To determine the oxidative stress level in peripheral blood of vanadium-exposed workers, as an indication of population health effect of vanadium on human neurobehavioral system. METHODS: 86 vanadium-exposed workers and 65 non-exposed workers were recruited by cluster sampling. A questionnaire was administered to collect demographic and occupational exposure information. Serum activity of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS) and malonaldehyde (MDA) contents were detected by kit assay. The differences in oxidative stress level between vanadium-exposed and non-exposed workers were compared. RESULTS: Vanadium-exposed workers had higher levels of MDA contents than the controls. The total superoxide dismutase(T-SOD) activity in vanadium-exposed workers was significantly lower than that in the controls, which was associated with lowered levels of manganese superoxide dismutase (Mn-SOD) activity. No changes in serum levels of cupro-zinc superoxide dismutase (CuZn SOD) was found in vanadium-exposed workers. No difference in iNOS activity was found between vanadium-exposed workers and controls. CONCLUSION: Vanadium exposure increases free radical production in serum and reduces antioxidant capacity. But the relationship between vanadium exposure and iNOS damage remains uncertain. PMID- 26867321 TI - [Lesion Locations and Quality of Life in Patients with Ischemic Stroke]. AB - OBJECTIVE: To determine the relationship between lesion locations and quality of life (QOL) in patients with ischemic stroke. METHODS: The QOL of 456 stroke survivors was assessed two years after the occurrence of stroke. The EQ-5D was used for measuring QOL. Lesion locations of the patients were identified with CT, MRI and clinical features. Risk factors associated with QOL were identified using a multi-level model. RESULTS: Among the 456 stroke survivors, 61.62% (3/5) had ACI lesions, and more than half of ACI occurred in the subcortex. The number of stroke survivors with left and-right hemisphere lesions was almost equal. Different QOL was found between stroke survivors with a right-side brain lesion and those with non-brain lesions (P<0.001). Significant differences in QOL were also found between those with a subcortex of anterior circulation lesion and others (P<0.044). CONCLUSION: Lesion locations are associated with QOL. Future studies should pay attention to lesion locations classified by vascular territory and brain anatomical structures and size of lesions. PMID- 26867322 TI - [High Risk Sex Behaviors and Associated Factors in Young Men in Chengdu]. AB - OBJECTIVE: To determine the prevalence of high risk sex behaviors and associated factors in 18-34 years old men in Chengdu. Methods An anonymous questionnaire survey was conducted in 18-34 years old men selected by multi-stage random sampling in Chengdu. Data of 1536 respondents who reported having sex contacts were analyzed. RESULTS: 23.6% of respondents had multiple sex partners in the past 12 months; 11.8% were involved commercial sex; 9.0% had group sex; 4. 7% had anal sex; 15.6% had never used a condom; 37.7% had sex under the influence of alcohol or drugs. Logistic regression analysis revealed that marital status [married, standardized partial regression coefficient (B) = -0.086, P<0.05] , level of education (bachelor or above, B= -0.063, P<0.05), frequency of exposure to pornography (B=0.058, P<0.05), childhood sexual abuse (B= 0.042, P<0.05), first sexual intercourse at an earlier age (B=0.162, P<0.05), frequency of sex under the influence of alcohol or drugs (B=0.054, P<0.05) were significant predictors of having multiple sexual partners. Sexual orientation, age, smoking, alcohol abuse, drug use, anxiety, depression, childhood physical abuse did not appear to be significant factors associated with having multiple sexual partners. CONCLUSION: Having multiple sexual partners is the main high risk sex behavior of young men in Chengdu. Childhood sexual abuse and early start of sexual intercourse are the major predictors of having multiple sexual partners. PMID- 26867323 TI - [Knowledge-Attitude-Practice and Associated Factors of Cancer Patients with Peripherally Inserted Central Catheter]. AB - OBJECTIVE: To investigate the Knowledge-Attitude-Practice (KAP) of cancer patients with peripherally inserted central catheter (PICC) and its associated factors. METHODS: A cross-sectional study was undertaken in 650 cancer patients with PICC in the West China Hospital, Sichuan University, from April 2014 to March 2015. Data were collected through a self-designed questionnaire in relation to KAP and its associated factors. RESULTS: A total of 619 valid questionnaires were returned. The participants had an average score of 9.28 +/- 2.04 in knowledge, 27.95 +/- 4.17 in attitude, and 25.67 +/- 4.00 in practice. Occupation was associated with catheter-related knowledge. Comorbidity (with diabetes, hypertension and coronary heart disease) was associated with catheter-related attitudes (P=0.040). Gender (P=0.015) and catheter insertion site (P=0.023) were associated with PICC practice. The multivariable linear regression model showed that female patients (standardized partial regression coefficient = -0.097, P = 0.024) and those with a higher level of education (standardized partial regression coefficient=0.125, P=0.017) had a higher score in PICC practice. CONCLUSION: Overall, a high level of KAP was found in cancer patients with PICC. Clinical nursesshould provide personalized catheter-related education for patients according to their gender and level of education. Special attention should be paid to those with comorbidities such as diabetes mellitus, hypertension, coronary heart disease and other chronic diseases. PMID- 26867324 TI - [The Relationship Between the Damages of Hand Functions and the Type of Cerebral Palsy in Children]. AB - OBJECTIVE: To investigate the relationship between the damages of hand functions and the type of cerebral palsy (CP) in children with CP. METHODS: A total of 280 children aged 4-12 years old with CP in the 20 districts of Chengdu were included. The damages of hand functions were assessed with the Chinese Version of Manual Ability Classification System (MACS) and its relationship with the type of CP were analyzed. RESULTS: Among the 280 investigated children, there were 195 chidren with spastic CP, which accounted for the largest proportion (69.64%), wherein the spastic diplegia was most common (56.41%). The classification of MACS was level I-II in 65.13% children with spastic CP, whereas the classification of MACS was level IU-V in 84. 44% and 80.95% children with mixed and dyskinetic CP, respectively. With the increase of the degree of cognitive dysfunction in children with CP, the level of MACS was also increased. There was a difference between the classification of MACS and the different type of CP (P<0.05). The children with spastic CP were mostly mild hand dysfunction, while the children with mixed and dyskinetic type of CP were mostly middle and severe hand dysfunction. A positive correlation was found between the MACS and the subtype of spastic CP (r=0.541, P<0.05). In most of the children with diplegia from spastic CP, the hand dysfunction was mild, whereas the children with quadriplegia from spastic CP were mostly middle and severe hand dysfunction. CONCLUSION: There was a correlation between the MACS and the type of CP which can be used to determine the damaged condition of hand functions and develop the program of rehabilitation and the measures of classification management for the chidren with CP. PMID- 26867325 TI - [Correlations Between Joint Proprioception, Muscle Strength, and Functional Ability in Patients with Knee Osteoarthritis]. AB - OBJECTIVE: To establish correlations between joint proprioception, muscle flexion and extension peak torque, and functional ability in patients with knee osteoarthritis (OA). METHODS: Fifty-six patients with symptomatic knee OA were recruited in this study. Both proprioceptive acuity and muscle strength were measured using the isomed-2000 isokinetic dynamometer. Proprioceptive acuity was evaluated by establishing the joint motion detection threshold (JMDT). Muscle strength was evaluated by Max torque (Nm) and Max torque/weight (Nm/ kg). Functional ability was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) questionnaire. Correlational analyses were performed between proprioception, muscle strength, and functional ability. A multiple stepwise regression model was established, with WOMAC-PF as dependent variable and patient age, body mass index (BMI), visual analogue scale (VAS)-score, mean grade for Kellgren-Lawrance of both knees, mean strength for quadriceps and hamstring muscles of both knees, and mean JMDT of both knees as independent variables. RESULTS: Poor proprioception (high JMDT) was negatively correlated with muscle strength (P<0.05). There was no significant correlation between knee proprioception (high JMDT) and joint pain (WOMAC pain score), and between knee proprioception (high JMDT) and joint stiffness (WOMAC stiffness score). Poor proprioception (high JMDT) was correlated with limitation in functional ability (WOMAC physical function score r=0.659, P<0.05). WOMAC score was correlated with poor muscle strength (quadriceps muscle strength r = -0.511, P<0.05, hamstring muscle strength r = -0.408, P<0.05). The multiple stepwise regression model showed that high JMDT C standard partial regression coefficient (B) = 0.385, P<0.50 and high VAS-scale score (B=0.347, P<0.05) were significant predictors of WOMAC-PF score. CONCLUSION: Patients with poor proprioception is associated with poor muscle strength and limitation in functional ability. Patients with symptomatic OA of knees commonly endure with moderate to considerable dysfunction, which is associated with poor proprioception (high JMDT) and high VAS-scale score. PMID- 26867326 TI - [Early Diagnosis And Endoscopic Minimally Invasive Treatment of Gastrointestinal Tumor]. AB - Gastrointestinal tumor could be aggressive and life threaten if it was not be diagnosed and treated at early stage. Digestive endoscopy plays a very important role in the early diagnosis and treatment of gastrointestinal tumor, and shows rapid evolution with novel technologies in the past years, such as endoscopic ultrasonography, magnifying endoscopy, electronic staining endoscopy, endoscopic confocal laser microscopy. Nowaday it becomes feasible to learn more about the endoscopic manifestation in early stage GI tumor. Besides, several new endoscopic surgical techniques, such as endoscopic submucosal dissection (ESD), endoscopicsubmucosal tunnel dissection (ESTD), submucosal tunneling endoscopic resection (STER), has been applied in clinical treatment of early stage GI tumor with curative effect. However, there are some new problems emerged, such as how to determine the depth of the lesion, how to avoid or reduce the incidence of postoperative complications, and how to standardize the pathological classification and the treatment of positive margin, which need multidisciplinary solution with the efforts from endoscopist, clinician and pathologist. With the deep insight on, molecular pathogenesis of GI tumor, new technologies combinding endoscopy, imaging and pathological measures, will promote more GI tumor early diagnosed and effectively treated, thus improve the survival and prognosis of GI tumor patients. PMID- 26867328 TI - [Factors Associated with Successful Submucosal Tunneling Endoscopic Resection Treatment for Upper Gastrointestinal Submucosal Tumors]. AB - OBJECTIVE: To determine the influence of location, depth and size of upper gastrointestinal (GI) submucosal tumors (SMTs) on the success of submucosal tunneling endoscopic resection (STER). METHODS: Patient records of 31 cases with upper GI SMTs who had STER between Jan. 1, 2014 and June 30, 2015 in West China Hospital of Sichuan University were retrieved. The success of STER was determined by its efficiency, complete resection rate, and incidence of complications. RESULTS: Of the 31 cases, 29 were treated successfully, with an average of (13.76 +/- 9.70) min and (32.00 +/- 27.35) min for tunnel formation of esophageal and stomach mucosal tumors respectively (P = 0.045). The 2 unsuccessful cases were gastric tumors. SMTs resection for mucous layer and muscularis propria took (17.50 +/- 9.06) min and (36.24 +/- 15.68) min, respectively (P=0.004). SMTs resection for tumors diameter < 2.0 cm and > or = 2.0 cm took (25.78 +/- 12.13) min and (39.73 +/- 19.23) min, respectively (P=0.023). Six cases of gastric tumors from muscularis propria had complications (19.4%) during or after surgery. CONCLUSION: Location, depth and size of upper GI SMTs has implications on duration of different STER stages, which may determine complete resection rate and incidence of complications. PMID- 26867327 TI - [The Efficiency and Complications of ESD and ESTD in the Treatment of Large Esophageal Mucosal Lesions]. AB - OBJECTIVE: To study the efficiency and complications of endoscopic submucosal dissection (ESD) and endoscopic submucosal tunnel dissection (ESTD) in the treatment of large esophageal mucosal lesions. METHODS: The clinical data were collected from the patients who received ESD or ESTD for the treatment of early esophageal lesions in our hospital during January 1, 2014 to July 15, 2015, including the en bloc resection rate, curative resection rate, postoperative complication rate, the risk factors of complications were explored by univariate and multivariate analysis. RESULTS: A total of 50 patients were involved in the study, ESD or ESTD were performed successfully in 53 times, including 6 cases of ESD,47 cases of ESTD, The average age was (61.9 +/- 6.8) yr., the average operating time was (83.57 +/- 32.33) min, the average dissected lesion was (14.82 +/- 3.18) cm2, En bloc resection rate was 94.34%, the curative rate was 84.90%. There were 1 case of bleeding, 1 case of perforation, 45 (84.90%) cases of fever, 13 cases (24.53%) of esophageal stricture. The severity of stricture was associated with the operation time Codds ratio (OR) = 1.040, 95% confidence interal (CI): 1.007-1.075) and esophageal circumference (OR=9.972, 95% CI: 1.221 81.416). The residual resection margin appeared in 8 patients, and the lesion area (OR=1.145, 95% CI: 1.013-1.294) was the only risk factor. CONCLUSION: ESD and ESTD are safe and effective in the treatment of early esophageal lesions, but seems have relatively high incidence of esopgageal stricture and residual resection margin in the treatment of large esophageal lesions. PMID- 26867329 TI - [Risk Factors of Lymph Node Metastasis in Superficial Esophageal Squamous Cell Carcinoma]. AB - OBJECTIVE: To analysis the risk factors of lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC). METHODS: The clinical data and pathological results of 344 SESCC patients, who underwent surgical treatments between January 2009 and December 2013 in West China Hospital, Sichuan University, were analyzed retrospectively. Clinicopathologic characteristics were compared between different histological types, and their possible relationships with LNM were explored by univariate and multivariate analysis. RESULTS: There were no LNM found in the patients with tumor limited to the mucous, tumor diameter <3 cm, highly and moderate differentiated SESCC. Univariate analysis showed that tumor diameter (P=0.004), depth of tumor invasion (P=0.009), histological type (P=0.030) and lymphatic involvement (P=0.002) were correlated with LNM. Multivariate analysis revealed that tumor diameter (P=0.007), depth of tumor invasion (P=0.003), histological type (P=0.010) and lymphatic involvement (P<0.001) were independent risk factors of LNM. CONCLUSION: To the patients with low risk of LNM, such as tumor limited to the mucous, tumor diameter <3 cm, and highly and moderate differentiation, endoscopic excision may be considered as an absolute indications. PMID- 26867330 TI - [Superficial Esophageal Carcinoma and Esophageal Intraepithelial Neoplasia: a Pathological Study of 130 Cases]. AB - OBJECTIVE: To identify the pathological features of superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected through endoscopic submucosal dissection (ESD). METHODS: The clinical and pathologic profiles of 130 cases were reviewed, including gross type, histology type, infiltration depth, infiltrative growth pattern, presence of tumor budding, lymphatic and vascular invasion, and margin status. RESULTS: The patients had a median age of 62 years old. The predominant gross type was mixed type (78/130, 60.0%), followed by Type 0-II (49/130, 37.7%). The longest diameter of lesionshad a median of 13.8 mm. Morphologically, there were 3 cases (2.3%) of undetermined dysplasia, 25 cases (19.2%) of low grade intraepithelial neoplasia, 56 cases (43.1%) of high grade of intraepithelial neoplasia, and 46 cases (35.4%) of invasive carcinoma. No correlation was found between histological type and gross type. Intramucosal and submucosal invasive carcinoma accounted for 87.0% (40/46) and 13.0% (6/46) of the cases, respectively; sm1 and sm2 accounted for 4.3% (2/46) and 8.7% (4/46) of the cases, respectively. Infiltrative growth pattern was identified as infiltrative growth pattern (INF) a (23/46, 50.0%), INFbeta (17/46, 37.0%) and INFc (6/46, 13.0%). Tumor budding was found in 3 cases and lymphatic and vascular invasion was found in 2 cases. Margin was positive in 30 cases (23.1%). Invasive carcinomahad a higher margin positive rate (24/46, 52.1%) than low grade intraepithelial neoplasia (1/25, 4.0%) and high grade intraepithelial neoplasia (5/56, 89%) (P<0.001). No association between margin positivity and invasive pattern was found (P=0.208). Fifteen cases (11.5%) recurred, with invasive carcinoma being more likely to recur (17.4%, 8/46) than low grade intraepithelial neoplasia (8.0%, 2/25) and high grade intraepithelial neoplasia (8.9%, 5/56) (P<0.05). No association between margin positivity and recurrence rate was found (P= 0.590). CONCLUSION: The superficial esophageal carcinoma and esophageal intraepithelial neoplasia resected by ESD are predominantly mixed type under endoscope, with histological features of high grade intraepithelial neoplasia and invasive carcinoma. Invasive carcinomas are more likely to recur and present with a positive margin. PMID- 26867331 TI - [Correlation Between Endoscopic Macroscopic Type and Depth of Tumor Invasion for Superficial Adenocarcinoma of Esophagogastric Junction]. AB - OBJECTIVE: To investigate the clinicopathologic characteristics of superficial adenocarcinoma of esophagogastric junction (AEG), and to analyze the relationship between endoscopic macroscopic type and tumor depth for such cancers. METHODS: The clinical data of the 57 superficial AEG patients who underwent endoscopic resection or surgical operation between November 2008 and May 2015 in West China Hospital, Sichuan University were analyzed. Clinicopathologic features were compared between different depth of tumor invasion by univariate and multivariate analysis. RESULTS: The age ranged between 48 and 76 yr., with an average age of (63.0 +/- 6.8) yr.; 49 cases in male, 8 cases in female. The tumor size ranged between 3.0 and 40.0 mm, the average size was 16. 6 mm. The mucosal carcinoma was 28 cases, the submucosal carcinoma is 29 cases. There were no significant differences in age, gender, histological type and Siewert type in two groups, while there was statistical difference in tumor diameter (P=0.02) and endoscopic typing (P=0.02) between the two groups. The further multivariate analysis revealed that endoscopic macroscopic type (P=0.041) was an independent risk factor of superficial AEG invasion depth. The risk of submucosal invasion was 3.244 times in depressed type as.large as in elevated or flat type of the superficial AEG (95% confidence interval: 1.050-10.023). CONCLUSION: The endoscopic macroscopic type may be useful in accurately diagnosing superficial AEG invasion depth. For the endoscopic macroscopic type mainly of depression, especially the type 0-III, which was more likely to infiltrate the submucosal and more likely to have lymph node metastasis, do not recommend to get an endoscopic treatment. PMID- 26867332 TI - [Detecting Thallium in Water Samples using Dispersive Liquid Phase Microextraction-Graphite Furnace Atomic Absorption Spectroscopy]. AB - OBJECTIVE: To develope a method of solvent demulsification dispersive liquid phase microextraction (SD-DLPME) based on ion association reaction coupled with graphite furnace atomic absorption spectroscopy (GFAAS) for detecting thallium in water samples. Methods Thallium ion in water samples was oxidized to Tl(III) with bromine water, which reacted with Cl- to form TlCl4-. The ionic associated compound with trioctylamine was obtained and extracted. DLPME was completed with ethanol as dispersive solvent. The separation of aqueous and organic phase was achieved by injecting into demulsification solvent without centrifugation. The extractant was collected and injected into GFAAS for analysis. With palladium colloid as matrix modifier, a two step drying and ashing temperature programming process was applied for high precision and sensitivity. RESULTS: The linear range was 0.05-2.0 microg/L, with a detection limit of 0.011 microg/L. The relative standard derivation (RSD) for detecting Tl in spiked water sample was 9.9%. The spiked recoveries of water samples ranged from 94.0% to 103.0%. CONCLUSION: The method is simple, sensitive and suitable for batch analysis of Tl in water samples. PMID- 26867333 TI - [The Effect of Fennel Tea Drinking on Postoperative Gut Recovery after Gynecological Malignancies Operation]. AB - OBJECTIVE: To reveal if whether fennel fruit (Fructus Foeniculi) tea drinking enhances the recovery of intestinal function after gynecologic malignancies operation. METHODS: A total of 159 patients undergoing laparotomy for gynecological cancers were randomized into a tea group (n=78) and a control group (n=81). The patients in tea group drank a cup of fennel fruit tea while patients in control group drank the equal quantity of water twice per day from the first morning after operation until the first flatus. Every cup of tea consists of 5 gram of dried fennel fruit and 130 mL boiled water. The patents only drank the filtrate. Groups were compared in terms of time to first flatus and defecation, postoperative hospital stay, length of parenteral nutrition, ileus symptoms and other postoperative complications. RESULTS: Postoperative hospital [(5.6 +/- 1.2) d vs. (6.7 +/- 2.0) d, P<0.001], the mean time to flatus [(53.1 +/- 11.3) h vs. (64.2 +/- 13.6) h, P<0.001)], and the mean time to defecation [(4.3 +/- 1.0) d vs. (5.4 +/- 1.2) d, P < 0.001)] were significantly lower in tea group compared with those in control group. Ileus symptoms were observed more in patients in the control group compared to patients in tea group [relative risk = 2.6; 95% confidence interval, 1.5-4.5; P=0.001]. CONCLUSION: Fennel tea drinking after laparotomy for gynecological malignancis, an economical care, is safe, well to lerated and associated with rapider recovery of bowel motility, shorter hospital stay and fewer complications. PMID- 26867334 TI - [Clinical Pathological Analysis of 29 Cases of Borderline Ovarian Tumors with Intraepithelial Carcinoma]. AB - OBJECTIVE: To investigate the clinicopathological characteristics, prognosis and the pregnancy condition after preserving fertility function surgery of borderline ovarian tumors with intraepithelial carcinoma (OIC). METHODS: Clinical data of 29 patients with OIC at Department of Gynecology, West China Second University Hospital, Sichuan University, between January 2005 and March 2014, were collected for retrospectively analysis with 6-93 months follow-up. The recurrence rate and pregnancy rate after preserving fertility function surgery were compared. RESULTS: OIC patients accounts for 4.0% (29/719) in borderline tumors patients, including fertility preserving function requirement 51.7% (15/29). All patients underwent surgery treatment, including conservative surgery 51.7% (15/29), radical surgery 48.3% (14/29). Adjuvant chemotherapy 27.6% (8/29). Pathological types: mucinous 69.0% (20/29), serous 13.8% (4/29), endometrioid 6.9% (2/29) and mixed 10.3% (3/29). FIGO stage: I a 75.9% (22/29), I b 17.2% (5/29), I c 6.9% (2/29). The average follow-up time was 49.6 months, the recurrence rate was 10.3% (3/29), the pregnancy rate was 66.7% (10/15). The recurrence rate of higher stage and intraoperative retaining ovaries was higher (P = 0.005, P = 0.005); the pregnancy rate of younger patients was higher (P=0.017). CONCLUSION: OIC patients are young, diagnosed at an early stage. Pathological types are mainly mucinous. For patients with fertility requirements, the recurrence rate of ovarian tumor excision surgery is very high. PMID- 26867335 TI - [Dual Cycle and Dual Channel Regimen in the Treatment of Severe Ovarian Hyperstimulation Syndrome with Pregnancy]. AB - OBJECTIVE: To explore the therapeutic effects and advantages of dual channel and dual cycle regimen in the treatment of severe ovarian hyperstimulation syndrome (OHSS) with pregnancy. METHODS: This study enrolled 60 severe OHSS patients who were successfully pregnant with vitro fertilization-embryo transfer (IVF-ET). The patients were divided into conventional single cycle treatment group (Group A) and dual cycle and dual channel treatment group (Group B). Before the treatment and at the 3rd d and 9th d of treatment, all the patients received the measurements of body mass (BM), abdominal circumference (AC), maximum depth of ascites in ultrasonic (D), serum albumin (ALB), Na+ concentration, white blood cell count (WBC), hematocrit (HCT), drink intake (Intake) and urine volume. The hospital days and costs, the times of paracentesis, the amount of albumin used and pregnancy outcomes were compared at discharge day. RESULTS: At the 3rd d of treatment, the changes of BM and HCT between the two groups had not significant difference, but AC and WBC were reduced in both groups, and Group B reduced more (P<0.05). At the 9th d of treatment,both groups had HCT, AC, D and WBC reduced as well as urine-volume and Intake increased, Group B showed more changes (P<0.05). Compared to the levels of ALB before treatment, it was lower at the 3rd d but higher at the 9th d in both group, with more changes found in Group B (P<0.05). Compared with Group A, Group B had shorter hospital day, less use of album and paracentesis (P<0.05). All patients in Group B were successful pregnant, one patient in Group A terminated pregnancy because of poor treatment effect. CONCLUSION: Dual-circulation and dual-channel therapeutic regimen could improve hypoproteinemia, low osmotic pressure, low blood volume for OHSS patients. PMID- 26867336 TI - [ED50 of Intrathecal Isobaric Bupivacaine with Epidural Volume Extension for Cesarean Delivery]. AB - OBJECTIVE: To determine the 50% effective dose (ED50) of intrathecal isobaric bupivacaine in combined spinal-epidural anaesthesia with epidural volume extension for caesarean surgery. METHODS: Eighty-four women undergoing elective caesarean sections were randomly assigned to seven groups, receiving intrathecally isobaric bupivacaine in a dosage of 6, 7, 8, 9, 10, 11 or 12 mg (n=12 per group), respectively. Ten mL normal saline was injected through an epidural catheter at a rate of 0.5 mL/s. Successful induction was defined as Hollmen pinprick block grade 2 at a height equal to or higher than T6. Success (surgery) was defined as success (induction) plus no requirement for epidural supplementation throughout surgery. The ED50 values were determined using a logistic regression model. RESULTS: The EDs for success (induction) and success (surgery) were 8.121 mg (95% confidence interval: 7.421-8.821) and 9.012 mg (95% confidence interval: 7.747-10.280), respectively. With increase in amount of intrathecal bupivacaine, time to success (induction) was shortened (P<0.05), resulting in increased successful numbers for both induction and surgery. No differences were found in the use of phenylephrine, haemodynamic stability and the occurrence of nausea and vomiting among groups. CONCLUSION: When combined with epidural volume extension, intrathecal bupivacaine has an ED50 of 8.121 mg and 9.012 mg for success (induction) and success (surgery), respectively, in women undergoing caesarean sections. PMID- 26867338 TI - The Role of Hospitals for end of life care. PMID- 26867337 TI - [Prevention Effect of Thymosin-alpha1 Aganist Early Ventilator-associated Pneumonia in Patients with Mechanical Ventilation]. AB - OBJECTIVE: To investigate the preventive effects of thymosin-alpha1 against early ventilator-associated pneumonia (VAP) in the patients with mechanical ventilation. METHODS: Fifty two patients with expectancy of mechanical ventilation over 48 h were divided into routine therapy group (n=26) and thymosin therapy group (n= 26) in random. The patients in routine therapy group were given intensive care unit (ICU) conventional treatment, and the patients in thymosin therapy group were given thymosin treatment additionally (1.6 mg subcutaneous injection, qd X 7 d). The incidence and occurrence time of VAP were observed, and the time of mechanical ventilation and ICU stay were recorded. The levels of CD3+, CD4+, CD4+ /CD8+ T lymphocyte, CD14+ mononuclear cell human leukocyte antigens-DR (CD14+ HLA-DR) and procalcitonin (PCT) were detected before mechanical ventilation and at the 3d and 7th d after mechanical ventilation. RESULTS: The base line including the level of immunologic function had no difference between the two groups (P>0.05). The incidence of VAP in thymosin therapy group was lower than that in routine therapy group, but it was not significant difference (P>0.05). The durations of machine ventilation and ICU stay in thymosin therapy group were shorter than those in routine therapy group (P<0.05). The occurrence time of VAP in thymosin therapy group was significantly later than that in routine therapy group (P<0.05). At the 3rd and 7th d after mechanical ventilation, thymosin therapy group achived higher levels of CD3+, CD4+, CD4+ /CD8+ T lymphocyte and CD14+ HLA-DR than routine therapy group did (P<0.05). CONCLUSION: Thymosinal may be able to improve immunologic function and prevent the incidence of early VAP in the patients with mechanical ventilation. PMID- 26867339 TI - Understanding Global End-of-Life Care Practices: IHF 2014 Research Project. AB - This first-of-its kind survey of global end-of-life (EOL) practices uncovered major differences in how EOL care is defined, delivered, and measured. According to respondents from university hospitals and cancer centers in 17 countries, the primary challenges to providing effective EOL care are communication between clinicians and patients/families, cultural beliefs about death, entrenched staff beliefs about prolonging life, and lack of funding. However, many organizations are implementing improvements in EOL services that support hospital-wide identification of patients for whom such services are appropriate, screening to avoid needless aggressive therapies, enhanced provider education, and ways to assess quality of life for terminally ill patients. PMID- 26867340 TI - Introduction of an Advance Care Planning Clinic in a Regional Care Coordination Service. AB - Advance Care Planning is an increasingly important consideration in health care service provision. Barriers to Advance Care Planning including lower prioritization than clinical care, and the complex logistics of completing the documentation have been identified in the literature and clinical practice. The Chronic Care Program within Canberra Hospital and Health Services introduced mobile and outpatient Advance Care Planning Clinics for care coordinated patients with chronic diseases, to address some of these barriers and facilitate end-of life care discussion amongst this patient group. The implementation of the clinics was evaluated, looking at the practicality of running these clinics within existing resources and patient acceptability. The number of Statement of Choices completed was used as a marker of whether the clinics led to an increase in Advance Care Planning amongst this patient group. The introduction of the clinics received positive feedback from patients and was able to beimplemented without requiring additional external resources. Following introduction of the Advance Care Planning clinics, an increase in the proportion of patients with a completed a Statement of Choices was seen. PMID- 26867341 TI - Overcoming the Obstacles in Promoting Hospice Palliative Care--Sharing Experiences of the Taiwan Changhua Christian Hospital. AB - Hospice palliative care for terminal patients is necessary, yet challenges are on the way worldwide. This study demonstrated that hospice palliative care has been quickly developed in Taiwan due to the support of the National Health Insurance system, the promotion by civil societies and religious groups, patient's legal right for DNR, easier access to pain killers through medical prescription, and well-planned hospice staff training programs. This paper introduces how hospice consultation is provided by a comprehensive hospice palliative team at Changhua Christian Hospital to establish trust and cooperation with the medical team, and to improve hospice-palliative care referral and utilization rates. PMID- 26867342 TI - Palliative Care and legislation around dying. AB - Around the world forty million people a year need palliative care yet more than four in five of these have no access to basic analgesia with morphine. 6% of those dying with no pain relief are children. Those left behind carry with them the memory of the death and it can colour their future lives, making good palliative care an urgent public health issue around the world. Everyone providing healthcare needs core training in palliative care, including the fundamentals of pain and symptom relief. Governments must urgently address barriers to morphine availability and educators of health care professionals must eliminate myths and phobias, and teach good end of life care. PMID- 26867343 TI - Establishing Palliative Care across the AKDN Health Services: Opportunities and Challenges. AB - AKDN has one of the most comprehensive private not-for-profit health care systems in the developing world. It has state-of-the-art urban academic tertiary care centers, service hospitals and community based primary care centers spread across the most remote areas of Central and South Asia and East Africa. In response to a global initiative to make palliative care widely available, the AKDN is spearheading the integration of palliative care across its international health network. The scope includes specialist palliative care services in urban tertiary care centers across secondary and outreach programs to home based palliative care services. The ultimate goal is to develop a comprehensive structure of palliative care services which, in addition tofulfilling the vision of quality, also fulfills the needs of the communities that it serves. This article describes the international undertaking; its challenges and the key contextual design principles of the implementation. PMID- 26867344 TI - End of life care in Acute Geriatric Units: making decisions about sedation. AB - Decisions regarding sedation as part of End-of-life Care in Acute Geriatric Hospitals, especially considering their 10% mortality rate, require an extremely rigorous approach to ensure complete ethical and clinical conformity. Developing a sedation protocol which examines a series of ethical and clinical safeguards regarding the implementation of this therapeutic measure facilitates and improves the decision-making process and encourages reflection among the professionals involved. Here we examine whether the protocol established in our hospital for terminal sedation was appropriately applied for those patients who passed away over the course of one year in our unit, and who received sedation in their final days. PMID- 26867345 TI - Evolution of palliative care in the French Cancer Centers-Unicancer. AB - The French Cancer Centers (FCC) have a threefold mission, care research and education. Their specificity is multidisciplinary and comprehensive patient support at all stages of cancer. Innovation and research are at the heart of FCC action, but the care of patients in the palliative phase is a major and long-time concern. In each center there is an autonomous or integrated structure of palliative care in a service or Interdisciplinary Department of Support Care for the Patient in Oncology. These include, besides the hospice activity, chronic pain, psychooncology, social support, nutrition, functional rehabilitation, etc. Furthermore, the FCC have, in accordance with a secondary regulatory text to National Plans for palliative care, identified beds of palliative care (IBPC) in oncology day hospitals and in palliative care. In 2006 a Unicancer FCC group was established. One of the group's goals is to promote "early palliative care" together with other FCC teams. A common research dynamic has been implemented, ensuring the development of organizations and palliative culture. PMID- 26867346 TI - Eukaryotic non-coding RNAs: new targets for diagnostics and therapeutics? AB - Non-coding RNAs (ncRNAs) in eukaryotes have recently developed to a very active research area in RNA biology, opening up new strategies for diagnosis and therapies of human disease. Here we introduce and describe the most important classes of eukaryotic ncRNAs: microRNAs (miRNAs), long non-coding RNAs (IncRNAs), and circular RNAs (circRNAs). We further discuss new RNA-based diagnostic and therapeutic concepts. PMID- 26867347 TI - Chemical modification of nucleic acids as a key technology for the development of RNA-based therapeutics. AB - RNA-based effector molecules (nucleic acid effectors) are important tools in molecular medicine because they offer a strategy to address therapeutically interesting targets that are not "druggable" with classic small molecule inhibitors. However, for in vivo applications, RNA-based effectors require specific chemical modifications to improve their stability and pharmacokinetic properties, as well as to minimize toxic and unspecific off-target effects. PMID- 26867348 TI - Circulating RNAs in medical diagnostics and as disease-relevant biomarkers. AB - The development of malignant tumors from healthy tissues is associated with profound changes in expression profiles of a large number of mRNAs, miRNAs and IncRNAs. These changes on the one hand permit insights into the biology of individual tumors; on the other hand, tumor-derived RNAs can also be detected in circulating blood and serve as specific markers for differential diagnosis and patient prognosis. PMID- 26867349 TI - Therapeutic delivery of RNA effectors: diseases affecting the respiratory system. AB - Although there are several hurdles to overcome on the way to the lung, this target organ provides several advantages for successful drug absorption. Recent findings in this field of research give reason to assume that the pulmonary delivery of RNA effector molecules holds a promising potential for the treatment of numerous severe respiratory diseases. PMID- 26867350 TI - Nanoparticle-mediated delivery of small RNA molecules in tumor therapy. AB - In principle, RNA interference (RNAi) allows for the inhibition of any oncogene of choice, thus leading to novel concepts in tumor therapy. For their delivery, the RNAi-inducing small RNA molecules (small interfering RNAs, siRNAs) can be formulated in various nanoparticle systems, prior to testing them in preclinical animal models. The same is true for miRNAs that have more recently been explored in therapeutic miRNA replacement strategies. This puts high demands on the properties of the nanoparticles. This review article discusses various nanoparticulate systems for RNA delivery in vivo and gives an overview of preclinical studies on siRNA- or miRNA-based tumor therapy. PMID- 26867351 TI - RNAi as a tool for target discovery in early pharmaceutical research. AB - The pharmaceutical industry is currently faced with increasing pressure due to patent expirations for block busters, healthcare reforms with strained budgets and growing demands for approval by administrative organizations like the FDA and the EMA. High attrition rates especially in the later expensive stages of the drug development process ask for thoroughly validated drug targets at the beginning of such projects. The great potential of RNA interference strategies toward reaching this goal is outlined in this article. PMID- 26867353 TI - SOUTHEAST ASIAN MINISTERS OF EDUCATION ORGANIZATION (SEAMEO). PMID- 26867352 TI - Actively personalized cancer vaccines--the step into clinical application. AB - Cancer vaccine development enters a new phase of innovation based on the development of modern sequencing technologies and novel RNA-based synthetic drug formats which enable the analysis and therapeutic targeting of every patient's tumor genome. By applying and combining these innovations, we have brought the concept of "actively personalized cancer vaccines" to clinical testing. Synthetic RNA is used as the drug format, allowing affordable, individual "on demand" manufacturing of tumor-optimized vaccines. PMID- 26867354 TI - SOCIO-DEMOGRAPHIC CHARACTERISTICS AND GEOGRAPHIC DISTRIBUTION OF REPORTED MALARIA CASES IN BANGKA DISTRICT, BABEL ISLAND PROVINCE, INDONESIA DURING 2008-2012. AB - Malaria is a major health problem in many developing countries including Indonesia. The purpose of this study was to investigate the socio-demographic characteristics and geographic distribution of malaria cases in Bangka District, Bangka-Belitung Island Province, Indonesia. Bangka District is a malaria endemic area of Indonesia. We analyzed the epidemiological data of all reported malaria cases during 2008-2012 in Bangka District. Of the 4,756 malaria-confirmed cases reported during the study period, 3,234 (68. 0%) were among persons aged >= 15 years, 1,024 (21.5%) were among persons aged 5-14 years and 498 (10.5%) were among persons aged < 5 years. Malaria cases were primarily located along the sea coast and less frequently in inland. Malaria cases were found not only among the local population but also among migrant workers. The monthly incidence of reported malaria cases in the study population ranged from 0.06 to 1.06 per 1,000 person-months. The cases were mostly due to Plasmodium vivax (57.1%) followed by Plasmodiumfalciparum (40.2%). Plasmodiumfalciparum was more common among migrant workers while Plasmodium vivax was more common among the local population (Odds ratio 1.2; p = 0.03). The main transmission vector found in the coastal area was Anopheles sundaicus. An. letifer and An. barbirostris were found inland. We identified "malaria hot-spots" in the study area using a Geographic Information System. The results of this study will contribute to the malaria control program. PMID- 26867356 TI - BIOEFFICACY OF A LONG-LASTING INSECTICIDE IMPREGNATED NET AGAINST ANOPHELES MACULATUS THEOBALD AND CULEX QUINQUEFASCIATUS SAY. AB - This study was conducted to evaluate the bioefficacy and effects of unwashed and washed PermaNet(r) 2.0 nets treated with extrinsic heat during washing against mosquitoes under laboratory condition. The effectiveness of the washed nets was bioassayed soon after washing using the WHO cone test method. The results indicated that the treated nets exhibited high durability to washing (five washes) and persistent bioefficacy against An. maculatus on both unwashed and washed nets. The unwashed net exhibited mortality of 98.33 +/- 2.06%, with KT50 and KT90 ranging from 17.57-to-66.38 minutes and 34.65-to-311.30 minutes, respectively (n = 9) for > 44 months. Nets washed at 30 degrees C for three successive washes exhibited mortality of 98.00 +/- 2.65% (n = 3) for 7 months. Twenty-one months later, two washes at 80 degrees C on the same nets caused a mortality of 87.50 +/- 3.54% (n = 2). The overall cone mortality of five washes over a total wash period of 33 months was 94.75 +/- 6.85% with KT50 and KT90 ranging from 23.98 to 58.25 minutes and 51.63 to 230.21 minutes, respectively (n = 5). However, the treated net exhibited lower bioefficacy against Culex quinquefasciatus on the unwashed nets with mortality of 9%. KT50 and KT90 ranged from 129.17 to 136.78 minutes and 315.35 to 716.05 minutes, respectively, over an unwashed period of 3 months (n = 1), and washed nets had a mortality of 30%; KT50 of 64.04 minutes and KT90 of 347.56 minutes for only one wash at 30 degrees C (n = 1). Application of extrinsic heat treatment during washing at 30 degrees C followed by increased heat at 80 degrees C on the same net did not enhance any significant increase in mortality of An. maculatus and Culex quinquefasciatus (p > 0.05). There was a difference in the delayed knock down time soon after washing at 80 degrees C. Based on these promising results, the PermaNet(r) 2.0 should be field-tested. PMID- 26867355 TI - TOXOPLASMA AND VIRAL ANTIBODIES AMONG HIV PATIENTS AND INMATES IN CENTRAL JAVA, INDONESIA. AB - In Indonesia, Toxoplasma and its associations with blood-borne viruses have been poorly studied. In order to study the association between anti-Toxoplasma antibodies and blood-borne viral antibodies, blood samples from 497 participants (375 inmates from four prisons in Central Java, Indonesia and 122 HIV patients at a Voluntary Counseling and Testing Clinic in Surakarta, Indonesia) were tested for serological markers of Toxoplasma, human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and human T-lymphotropic virus types I and II (HTLV-1/2). Anti-Toxoplasma IgG and IgM positivity rates were 41.6% and 3.6%, respectively. One point two percent of participants was positive for both anti-Toxoplasma IgG and IgM antibodies. Sixteen point five percent, 11.3%, 2.6% and 2.8% of participants were positive for anti- Toxoplasma IgG combined with anti-HCV antibodies, anti-Toxoplasma IgG combined with anti-HIV antibodies, anti-Toxoplasma IgM combined with anti-HIV antibodes and anti-Toxoplasma IgG combined with both anti-HIV and anti-HCV antibodies, respectively. Anti-Toxoplasma IgM seropositivity was associated with anti-HIV (aOR = 4.3; 95% CI: 1.112-16.204, p = 0.034). Anti-Toxoplasma IgG antibodies were associated with anti-HCV (aOR = 2.8; 95% CI: 1.749-4.538, p < 0.001) and history of injection drug use (aOR = 3.1; 95% CI: 1.905-5.093, p < 0.001). In conclusion, we recommend patients with HIV, HCV infection and injection drug users should be screened for Toxoplasma infection in Indonesia. PMID- 26867357 TI - CHARACTERISTICS OF PHLEBOTOMINE SANDFLIES IN SELECTED AREAS OF SRI LANKA. AB - Cutaneous leishmaniasis (CL) is an endemic disease in Sri Lanka. Studies on vector aspects, although important for better understanding of disease transmission dynamics, are still limited. The present study describes the species distribution and behavioral patterns of sandflies within selected disease prevalent zones in the country. Adult sandflies were collected from several field sites over a two-year duration in Sri Lanka using cattle-baited net traps, CDC light traps and manual methods. Species identification was performed using standard keys. Leishmania donovani and source of blood meal in blood-fed female sandflies DNA were identified using PCR-based methods. Aggregation period of adult sandflies during overnight collections was also noted. The collected sandflies were identified as Phlebotomus argentipes glaucus (previously known as morphospecies A) and a non-vector species, Sergentomyia zeylanica. Presence of L. donovani DNA was found in 2/634 female sandflies. The parasite ITS1 region of SSU rDNA had 99% sequence similarity with L. donovani from Bangladesh and India. The peak aggregation period of sandflies within cattle-traps was between 8:00 PM to 11:00 PM, indicating that vector control strategies could be conducted during this time period. As Sergentomyia zeylanica is likely to be merely a biting nuisance and showed more of an anthropophilic behavior, whereas the probable vector of CL in Sri Lanka (P. argentipes glaucus) demonstrated zoophilic behavior, has implications for the planning of future vector control strategies. PMID- 26867358 TI - MOLECULAR DETECTION OF HUMAN BOCAVIRUS 1 AND 2 IN CHILDREN WITH ACUTE GASTROENTERITIS IN TAIWAN. AB - Human bocaviruses (HBoVs) have been detected in human gastrointestinal infections worldwide. Although HBoV global prevalence and strains diversity have been reported, but epidemiological data from Taiwan is largely unavailable to date. A total of 110 fecal samples from stools of diarrheic children at a general hospital, Taiwan, obtained from August 2012 to July 2013, were analyzed by nested PCR targeting a partial fragment (576 bp) of HBoV VP1/VP2 gene, which revealed 4 positive fecal samples. Clinical symptoms of HBoV-associated acute gastroenteritis (AGE) were not different from those without HBoV. HBoV infection was seen only during the fall and winter seasons. This is the first description of HBoV infection in children with AGE in Taiwan. Systematic surveillance and evidence-based studies are required to determine the transmission pathways and spread of HBoV in Taiwan. PMID- 26867359 TI - PREVALENCE OF HUMAN ENTEROVIRUS AMONG PATIENTS WITH HAND, FOOT, AND MOUTH DISEASE AND HERPANGINA IN THAILAND, 2013. AB - Human enterovirus (EV) infection causes hand, foot, and mouth disease (HFMD) and herpangina (HA). We studied the prevalence of enterovirus (EV) among patients with HFMD and HA in Thailand during 2013. We conducted a study in archived specimens of patients sent for screening for enterovirus. A total of 203 clinical specimens from 184 individuals with painful blister in the oropharynx and on the palms, soles, knees, elbows or buttock were examined by semi-nested polymerase chain reaction (PCR) for the 5'UTR and VP1 genes of EV. Eighty-six samples were positive: EV71 was detected in 14 (30%), CV-A8 in 12 (26%) and CV-A16 in 10 (21%). Classification of EV species detected revealed that 46 specimens were EV A, 14 specimens were EV-B, 1 specimen was EV-D, and 16 specimens were positive for unclassified enterovirus. The majority of individuals with EV infection were aged 2-6 years. Multiple EV-A serotypes were detected among HFMD and HA patients in our study. PMID- 26867360 TI - MOLECULAR CHARACTERIZATION OF VIRULENCE AND ANTIMICROBIAL SUSCEPTIBILITY PROFILES OF UROPATHOGENIC ESCHERICHIA COLI FROM PATIENTS IN A TERTIARY HOSPITAL, SOUTHERN THAILAND. AB - Among uropathogens, uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection (UTI) worldwide, but clinical aspects due to this bacterial species is not fully understood in southern Thailand. Two hundred fifty-four UPEC isolates from patients admitted to Maharaj Nakhon Si Thammarat Hospital, southern Thailand were examined for crucial virulence genes, showing that 33.5% contained at least one of the virulence, genes tested. Genes encoding P fimbria, cytotoxic necrotizing factor-1 and alpha-hemolysin constituted the majority (15.8%) carried by UPEC isolates. Phylogenetic group classification revealed that 57.5% of UPEC belonged to group D. Antimicrobial susceptibility tests showed that 70.5% and 65.1% of the isolates were resistant to ciprofloxacin and norfloxacin, respectively. Moreover, 50.0% of UPEC were capable of producing extended spectrum beta-lactamases. These findings should be of benefit for more appropriate treatment of UTI patients in this region of Thailand. Keywords: uropathogenic Escherichia coli, antibiotics resistance, cnfl, hlyA, pap, Thailand PMID- 26867361 TI - DETECTION OF NEW DELHI METALLO-BETA-LACTAMASE-1-PRODUCING KLEBSIELLA PNEUMONIAE AT A GENERAL HOSPITAL IN THAILAND. AB - The purpose of this study was to detect carbapenemase genes in clinical isolates of carbapenem-resistant Enterobacteriaceae (CRE) obtained from patients admitted to Hua-Hin Hospital, Prachuab Khiri Khan Province, Thailand between January and December 2014. Screening of CRE was initially determined using disk diffusion method, and subsequently using modified Hodge test (MHT). Multiplex PCR was employed to amplify carbapenemase genes, blaIMP, blaOXA-48, blaNDM blaKPC, and blaVIM. Of the 624 clinical isolates, seven CRE isolates were identified by the disk diffusion method, but were negative for MHT. Only one isolate, Klebsiella pneumoniae, was found to carry blaNDM-1, encoding New Delhi metallo-beta lactamase-1, and the remaining CRE isolates were negative for the carbapenemase genes looked at. However, monitoring of carbapenem resistance among Enterobacteriaceae should be for optimal infection control measures. PMID- 26867362 TI - PROSPECTIVE EVALUATION OF A NOVEL TWO-STEP PROTOCOL FOR SCREENING OF CLOSTRIDIUM DIFFICILE INFECTION IN HOSPITALIZED ADULT PATIENTS. AB - Abstract. Clostridium difficile infection (CDI) is one of the most common nosocomial infections in Thailand and worldwide. The clinical spectrum ranges from annoy- ing diarrhea to severe life-threatening disease. Enzyme-linked immunofluorescent assay for cytotoxins A/B (cytotoxins A/B ELFA), which has been widely used in our institute, generally is considered as having low sensitivity for diagnosis of CDI. The study was a prospective evaluation of a novel two-step diagnostic algorithm, in which the first step involved concurrent cytotoxins A/B ELFA and enzyme immunoassay for glutamate dehydrogenase (GDH EIA) for CDI, followed by PCR assay of tcdA and tcdB in samples with discordant results. Of the 91 adult patients (37 males and 54 females, mean age of 60.0 +/- 19.5 years) with suspected CDI hospitalized at King Chulalongkorn Memorial Hospital, Bangkok, Thailand from December 2012 to February 2013, 22 were diagnosed with CDI by the gold standard PCR test for tcdA and tcdB, among whom 21 were positive by GDH EIA, accounting for a sensitivity of 95%. Of the 69 patients without CDI, GDH EIA was negative in 46 patients, accounting for a specificity of 67%. The positive predic tive value (PPV), negative predictive value (NPV) and accuracy of GDH EIA was 48%, 98% and 74%, respectively, whereas sensitivity, specificity, PPV, NPV, and accuracy of cytotoxins A/B ELFA was 73%, 96%, 84%, 92% and 92%, respectively. Some 30% of specimens required the more expensive PCR assay. However, this two step protocol detected 20% more patients with CDI than the currently used cytotoxins A/B ELFA method. PMID- 26867363 TI - NOCARDIA BEIJINGENSIS PSOAS ABSCESS AND SUBCUTANEOUS PHAEOHYPHOMYCOSIS CAUSED BY PHAEOACREMONIUM PARASITICUM IN A RENAL TRANSPLANT RECIPIENT: THE FIRST CASE REPORT IN THAILAND. AB - We describe the first case of a psoas muscle abscess caused by Nocardia beijingensis and subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum in a renal transplant recipient. The patient was treated for nocardiosis with percutaneous drainage and intravenous trimethoprim/sulfamethoxazole (TMP/SMX) combined with imipenem for 2 weeks, followed by a 4-week course of intravenous TMP/SMX and then oral TMP/SMX. During hospitalization for the psoas muscle abscess the patient developed cellulitis with subcutaneous nodules of his right leg. Skin biopsy and cultures revealed a dematiaceous mold, subsequently identified as P. parasiticum by DNA sequencing. The subcutaneous phaeohyphomycosis was treated with surgical drainage and liposomal amphotericin B for 4 weeks followed by a combination of itraconazole and terbinafine. The patient gradually improved and was discharged home after 18 weeks of hospitalization. PMID- 26867364 TI - NOCARDIOSIS REVEALED BY THYROID ABSCESS AND PNEUMONIA IN A LIVER TRANSPLANT RECIPIENT. AB - Nocardia thyroid abscess with pneumonia is a rare clinical presentation. We reported a liver transplant recipient with Nocardia thyroiditis and pneumonia after receiving high dose immunosuppressants to preserve his graft. The patient is a 50-year-old male who developed hepatitis C virus-related liver cirrhosis and received a liver transplant. Seven months post-transplantation the patient developed graft rejection, which was treated with 3 days pulse dose methyl prednisolone followed by an increased dose of his tracolimus, mycophenolate and prednisolone. He presented to the hospital with a 2 week history of fever, tenderness in his anterior neck and dry cough. On admission his temperature was 39.5 degrees C. The right wing of his thyroid gland was swollen to 3 cm in size, fluctuant and tender. On auscultation of his lungs there were fine crepitations and increased vocal resonance in the right middle lung field. On laboratory testing, a complete blood count (CBC) revealed leukocytosis (19,900/mm3) with neutrophils (97%). A chest X-ray showed an patchy infiltrates and round circumscribed densities in the superior segment of the right lower lobe of his lung. A CT scan of his neck revealed a diffusely enlarged right wing of the thyroid gland, 3.8 cm in diameter that had an abnormal hyposignal area. A CT of his chest revealed consolidation of the superior segment of the right lower lobe and necrotic right paratracheal lymph nodes with inflamed strap muscles. Fine needle aspiration of the right lobe of thyroid gland was performed. Modified acid fast bacilli (MAFB) staining showed partially acid-fast beaded branching filamentous organisms and a culture grew out Nocardia asteroides. He was treated with trimethoprim-sulfamethoxazole for 6 months. He improved clinically and his chest X-ray also cleared. PMID- 26867365 TI - PLANT POISONING IN THAILAND: A 10-YEAR ANALYSIS FROM RAMATHIBODI POISON CENTER. AB - Plant poisoning is not uncommon in Thailand. The objective of this study was to determine the incidence, type, clinical manifestations, severity and outcomes of plant poisoned patients in Thailand over a 10-year period. We retrospectively reviewed data from the Ramathibodi Poison Center Toxic Exposure Surveillance System for 2001-2010. A total of 2,901 poisonous plant exposure cases were identified, comprising 3.1% of the 92,392 poison cases recorded during the study period. This was the fifth most common type of poisoning recorded. Children aged < 13 years comprised the largest percent (69.8%) of the cases. The major type of exposure was unintentional ingestion. Ninety-nine types of poisonous plants were recorded as the causative agents among 99.1%of the cases. Gastrointestinal symptoms were reported in 72.0% of cases with Jatropha curcas (physic nut) comprising 54.1% of these. Most patients had only minor signs and symptoms. The mortality rate among the total plant poisoning cases was 0.9%, with 26 deaths. Thirteen deaths occurred in children aged < 13 years. The greatest number of fatalities were due to ingestion of Manihot esculenta (cassava), primarily due to multi-system organ failure. Children aged < 13 years are at the greatest risk for plant poisoning in Thailand; mostly unintentional. Most cases were minor and the mortality rate was low. Jatropha curcas was the most common cause of poisoning and Manihot esculenta was the most common cause of death. Public education is important to minimize these poisonings. PMID- 26867366 TI - EQUITY AND SATISFACTION OF COMMUNITY HEALTH SERVICES IN TONGLIAO CITY, INNER MONGOLIA. AB - We aimed to describe the human resources and apparatuses of community health service (CHS) in Tongliao City of China and investigate the differences between CHS centers and stations. Field investigations and questionnaire-based surveys were conducted in 120 CHS organizations of Tongliao City, which were selected by a stratified multistage random cluster sampling method. Data were collected on the human resources, medical apparatuses, and satisfaction of covered residents. We found that the total number, educational background, and professional titles of staff were lower at stations than at centers. Although the categories of providing health services were comparable between centers and stations, stations provided fewer health services than centers did. In addition, stations owned fewer apparatuses compared with centers. The percentages of satisfaction on many items were lower among residents covered by stations than among those covered by centers. Desired health services provided by CHS organizations have been partially accomplished in Tongliao City. Attracting more highly educated professionals and purchasing more valuable apparatuses may be helpful to improve the unbalanced distribution in human resources and apparatuses between centers and stations. Appropriate modifications of corresponding policies should be taken into consideration by the local government in the future. PMID- 26867367 TI - ASSOCIATION BETWEEN MATERNAL BODY MASS INDEX AND WEIGHT GAIN WITH LOW BIRTH WEIGHT IN EASTERN THAILAND. AB - We conducted a retrospective study to determine the association between maternal body mass index and pregnancy weight gain with low birth weight newborns (LBWN) at Phrapokklao Hospital in eastern Thailand. We evaluated the files of 2,012 women who delivered at the hospital. Data obtained from the charts were parity, maternal age, body mass index (BMI), prepregnancy weight, weight gained during pregnancy, gestational age, hematocrit level, referral status, place of residence, fetal presentation, completion of antenatal care visits and maternal HIV infection. Sixty-five point two percent of subjects were aged 20-34 years old. Fifty-seven percent of subjects had a normal BMI and 13.2% were anemic. Thirty- seven point five percent, 32.9% and 29.6% gained too little, the correct amount and too much weight during pregnancy, respectively. Primiparity, too little weight gain and gestational age less than 37 weeks at delivery were all significantly associated with LBWN. Preterm babies were 25 times more likely to have a low birth weight than term infants (adjusted OR = 24.995; 95% CI: 16.824 37.133, p < 0.001). When maternal weight gain of any BMI group was inadequate, the subject had a 3.4 times greater risk (adjusted OR = 3.357; 95% CI: 22.114 5.332, p < 0.001) of having a LBWN. Primiparous women had a 1.7 times (adjusted OR=1.720; 95% CI: 1.182-2.503, p-0.005) greater risk of having a LBWN. The results from this study may be useful to plan maternal health programs for eastern Thailand. PMID- 26867368 TI - INFLUENCE OF PERCEIVED RISK OF SMOKING AND SECOND-HAND SMOKE ON SELF-REGULATORY BEHAVIOR AMONG PREGNANT TAIWANESE WOMEN. AB - Tobacco use is a global health problem, including in Taiwan. The present study evaluated the perceived risk of smoking and second-hand smoke among pregnant Taiwanese women using a questionnaire. Seven hundred twenty-four pregnant Taiwanese women were recruited from an online parenting community using convenience sampling in 2013. Pregnant smokers and non-smokers had significantly different perceptions regarding risk of smoking and second-hand smoke during pregnancy. Pregnant non-smokers adopted more behaviors to avoid second-hand smoke both at home and in public than pregnant smokers. We conclude that perceived fetal health risks from smoking and second-hand smoke influenced maternal behavior during pregnancy. Pregnant women's perceptions of the risk of tobacco smoke depended on whether their focus in the decision-making process was on prevention or promotion. Understanding the risk factors associated with smoking and exposure to second-hand smoke during pregnancy may help in developing strategies to reduce such exposure. PMID- 26867369 TI - PARENTAL KNOWLEDGE OF THE ADVERSE EFFECTS OF HOUSEHOLD TOBACCO SMOKE EXPOSURE IN ASTHMATIC CHILDREN. AB - The aim of this study was to determine the prevalence of household tobacco smoke exposure in children presenting to asthma clinic at Prapokklao Hospital and to survey parental knowledge and perception to the dangers of household smoke exposure. Parents/guardians who brought their children to asthma clinic during June-September 2014 were interviewed to complete survey questionnaires. If there were smokers in the household, questionnaires with a postage paid self-addressed envelopes were given to the family to take back home for other household smokers to complete. There were 149 asthmatic children who attended the asthma clinic during the study period. Seventy-one pediatric patients (47.7%) lived with at least one household smoker. Thirty-one smokers completed the questionnaires. Only five (16.1%) accompanied the patients to asthma clinic. Almost all of the smokers had a desire to quit smoking, and 58.1% of the smokers and 63.2% of the non smokers had received information regarding the dangers of household smoke exposure. The knowledge test scores were not different between the two groups. The prevalence of household smoke exposure in asthmatic children was high, despite most of the smokers knew about the adverse effects of household smoke exposure on their children' s health and desired to quit smoking. PMID- 26867370 TI - EPIDEMIOLOGY AND RISK FACTORS FOR NONFATAL DROWNING IN THE MIGRANT CHILDREN. AB - The purpose of this study was to determine the incidence and potential risk factors for nonfatal drowning among migrant workers' children in China. We conducted a cross-sectional survey of students from third to ninth grade at five Migrant Workers' Children schools in Ningbo, China in 2014. General information and a history of nonfatal drowning was obtained from self-reported questionnaires by migrant students. A multivariate logistic regression model was used to identify potential risk factors. A total 3,859 students were included in the current study. Of these, 13.4% had experienced a nonfatal drowning accident (15.2% for males, 11.2% for females). Most nonfatal drowning occurred in natural water settings. Diving into unknown water without adult supervision had the greatest association with history of nonfatal drowning [odds ratio (OR) = 1.97; 95% confidential interval (CI): 1.31-2.95], followed by fishing in water (OR = 1.50; 95% CI: 1.05-2.14), swimming or playing in water (OR = 1.47; 95% CI: 1.02 2.12), and trying to rescue peers in the water if they were drowning (OR = 1.31; 95% CI: 1.04-1.64). There were factors associated with a lower risk of drowing: having a parent accompany the child to school (OR = 0.69; 95% CI: 0.51 0.93),understanding the the danger of swimming alone (OR = 0.69; 95% CI: 0.48 0.99) and having a knowledge about water safety (OR = 0.98; 95% CI: 0.98-0.99). The study population was at inceased risk for nonfatal drowning. Preventive measures, such as improved water-safety knowledge, decreasing risky water-related activities and better supervision of children need to be developed and tested to decrease the risk of nonfatal drowning among the study population. PMID- 26867371 TI - WORK RELATED INJURY AND ILLNESS: EXPLORING THE RETURN-TO-WORK PROGRAM IN MALAYSIA. AB - Illness and injury have a significant impact on employees, their families and employers. The consequences faced by an injured worker could lead to disability, which could then lead to inability to work. This study examined the patterns of the Return to Work (RTW) using data from The Social Security Organisation (SOCSO) of Malaysia RTW database from 2010 to 2013. Factors of successful return to work, employees' salary upon returning to formal employment were also investigated. Gender, age, year of injury, industry, and job hierarchy were found to be significant predictors of employees' salary upon returning to work. Although there are other costs involved on the part of employers and employees, themselves, in the long term the financial returns that can be brought back by injured workers who have successfully returned to work combined with the qualitative benefits substantially outweighs the costs of RTW program. PMID- 26867372 TI - THE RELATIONSHIP BETWEEN INJURY SEVERITY AND INDIVIDUAL CHARACTERISTICS: A SURVEY IN SOUTHERN CHINA. AB - This study aimed to assess the relationships between road traffic injury severity and individual characteristics in Liuzhou, a city in southern China. Data for this study were collected from the Guangxi Public Security Bureau Traffic Police Corps. Multivariate ordinal logistic regression analysis was used. Of all 14,595 individuals involved in accidents, males, motor vehicle drivers, motorcyclists, and those aged 21-45 years accounted for the great proportion of all injuries. Children, the elderly, pedestrians, farmers and migrant workers, unemployed people, and novice drivers were at higher risk of serious injury in crashes. These findings suggest that individual characteristics (age, modes of transport, profession, driving experience) are strongly related to injury severity. To address road traffic related mortality and injuries, there is a need to develop policy strategies, strengthen road supervision, and improve public consciousness of road safety. PMID- 26867373 TI - CHARACTERIZATION OF MALARIA INFECTION AT TWO BORDER AREAS OF THAILAND ADJOINING WITH MYANMAR AND MALAYSIA. AB - During 2009 to 2010, a total of 408 blood samples collected from malaria patients in Ranong (149) and Yala (259) Provinces, Thailand were investigated for Plasmodium spp using microscopic examination. There are no statistical differences in the prevalence of P. falciparum and P. vivax in samples collected from Ranong and Yala (46% vs 52%, and 54% vs 45%, respectively). Single nucleotide polymorphism of codon 86 in pfmdr1 (encoding P. falciparum multidrug resistance protein 1) was investigated among 75 samples of P. falciparum and 2 samples of P. knowlesi. A pfmdr1 N86Y mutation was detected in 1 out of 29 samples and 45 out of 46 samples obtained from Ranong and Yala Provinces, respectively. It is interesting that pfmdr1 was detected in two P. knowlesi DNA samples obtained previously from Ranong Province which was 99% homologous to pfmdr1 obtained from falciparum parasites in the same area but the mutation was not observed. The difference in multidrug resistance protein in Plasmodium obtained from those two border areas of Thailand will be of use in monitoring drug resistance in these border regions of the country. PMID- 26867374 TI - INTRAOSSEOUS PROLIFERATIVE SPARGANOSIS PRESENTING AS A PATHOLOGICAL FRACTURE: A CASE REPORT AND REVIEW OF THE LITERATURE. AB - We report a case of 63-year-old male, who presented with pathological fracture of left distal humerus 3 weeks previously. The radiographic findings showed an ill defined permeative osteolytic lesion of the left distal humerus. Incisional biopsy and debridement was done; pathological examination revealed a folded cestode larva with calcareous corpuscles in the bone and soft tissue, and increased eosinophils. IgG antibody tests for sparganosis were positive. The patient refused to have surgery for internal fixation and placement of an endoprosthesis. PMID- 26867375 TI - DISTRIBUTION OF ENTOMOPATHOGENIC NEMATODES IN LOWER NORTHERN THAILAND. AB - Entomopathogenic nematodes (EPNs) are used successfully for biological control of subterranean larval pests leading to reduced environmental contamination if chemical control measures are employed. Their diversity and distribution in Thailand are unclear, so the present study sought to obtain a better understanding these EPN populations in the lower northern region of Thailand. We collected 930 soil samples from 186 sites of Kamphaeng Phet, Nakhon Sawan, Phetchabun, Phichit, Phitsanulok, Sukhothai, Tak, Uthai Thani, and Uttaradit Provinces, Thailand from December 2011 to November 2012. Galleria mellonella was used as host for isolating and propagating EPNs. Seventy soil samples (7.5%) yielded EPNs of two genera, Steinernema (3.0%) and Heterorhabditis (4.5%). The majority of the isolated EPNs were found in loam at 26 degrees C-33 degrees C and pH values of 5.0-7.0. Molecular identification from partial 28S rDNA sequences revealed S. websteri, isolated from soil samples from Nakhon Sawan and Uthai Thani. Phylogenetic analysis of these EPNs showed they are closely related to S. websteri JC1032. The identification that S. websteri was the predominant EPN should enable its application for biological control in the local prevailing soil conditions. PMID- 26867376 TI - TEMPORAL CHANGES OF AEDES AND ARMIGERES POPULATIONS IN SUBURBAN AND FORESTED AREAS IN MALAYSIA. AB - Surveillance of mosquitoes and their distribution in association with rainfall, relative humidity, and temperature were conducted in selected suburban and forested areas, namely, Sungai Penchala (Kuala Lumpur) and Taman Alam (Selangor) for 12 months. Armigeres kesseli was the most abundant species in Sungai Penchala while Aedes butleri was the most dominant species in Taman Alam. A positive correlation between mosquito distribution and rainfall was observed in selected mosquito species in Sungai Penchala (Armigeres kesseli, r = 0.75; Armigeres subalbatus, r = 0.62; and Aedes albopictus, r = 0.65) and Taman Alam (Armigeres sp, r = 0.59; Ae. butleri, r = 0.85; and Ae. albopictus, r = 0.62). However, no significant cor- relation was found either between selected mosquito species in both study areas and relative humidity or temperature. Results obtained suggested that vector control programs to be conducted based on temporal distribution of vectors in order to achieve beneficial outcomes with effective costing. PMID- 26867377 TI - SCREENING FOR MOSQUITO LARVICIDAL ACTIVITY OF THAI MUSHROOM EXTRACTS WITH SPECIAL REFERENCE TO STECCHERINUM SP AGAINST AEDES AEGYPTI (L.) (DIPTERA: CULICIDAE). AB - For over 50 years, biological control of mosquito larvae has depended mainly on plant extracts, fish, bacteria, protozoa, filamentous fungi, viruses or nematodes. In this study, we screened 143 mushroom samples from 44 confirmed species in Thailand for their mosquito larvicidal activity. One g% (w/v) aqueous extracts of dried powdered mushroom samples were tested against 3rd stage Aedes aegypti larvae. Four mushroom species, namely, Thaeogyroporus porentosus, Xylaria nigripes, Chlorophyllum sp and Steccherinum sp, and two unidentified species showed larvicidal mortality ranging from 10%-70% and 18%-90% for 24- and 48-hour exposure time, respectively. Steccherinum sp aqueous crude extract, after 48-hour exposure, did not show any larvicidal activity at 1,000 ppm, whereas that from ethanol, after 24-hour exposure, had 50% and 90% lethal concentration of 203 ppm and 412 ppm, respectively, with higher levels of mortality after 48- hour exposure. This is the first report of mosquito larvicidal properties of Thai mushroom extracts. PMID- 26867378 TI - LARVICIDAL POTENTIAL AND MOSQUITO REPELLENT ACTIVITY OF CASSIA MIMOSOIDES EXTRACTS. AB - This study aims to investigate larvicidal activities of extracts of Cassia mimosoides leaves and pods as a potential agent in vector control of malaria and to evaluate repellent effect against Anopheles gambiae mosquito of the extract formulated in an aqueous cream base. Petroleum spirit, ethanol, water and dichloromethane extracts were tested against third and fourth instar Anopheles gambiae larvae. The petroleum extract was formulated in an aqueous cream base and repellency determined using N-N-diethyl-m-toluamide (DEET) as control. Phytochemical analysis showed the presence of saponins, tannins, anthraquinones, steroids, and flavonoids but absence of cardiac glycosides and alkaloids in powdered C. mimosoides. A dose related response was observed in the mortality rate of the extracts, with 2 mg/ml petroleum ether and dichloromethane extracts achieving 100 % mortality. Larvicidal activity of extracts based on LC50 values was petroleum ether > dichloromethane > ethanol > water. The formulated petroleum ether extract cream had a characteristic odor, hard and smooth texture, skin feeling of smoothness, ease of application by rubbing, easy removal using soap and water, non-irritating effect on skin and an acceptable pH value. The cream containing 2%-6% (w/w) extract and control achieved 100% repellency against mosquitoes after an exposure time of 5 minutes. There was a linear relationship between percent concentration of plant extract in the cream samples and repellent activity. These results suggest that crude extracts of C. mimosoides can be developed as eco-friendly larvicide and mosquito repellent and encourage further effort to investigate the bioactive compounds in the extracts. PMID- 26867379 TI - EVALUATION OF A COMMERCIAL RAPID TEST KIT FOR DETECTION OF ACUTE DENGUE INFECTION. AB - Early diagnosis is important for clinical management of dengue disease. While classic laboratory tests are often tedious and time consuming, point of care devices offer a rapid, cost-effective and user-friendly alternative provided their accuracy is acceptable. This study evaluated the sensitivity, specificity and efficiency of SD BIOLINE Dengue Duo(r) rapid NS1, IgM and IgG test kit for diagnosis of acute dengue virus infection. Standard laboratory diagnostics, RT PCR, IgM and IgG capture ELISAs were carried out on 143 suspected dengue patient samples obtained from a Sri Lankan population. Using the results of these standard laboratory tests as reference, the sensitivity and specificity of the SD Dengue Duo(r) NS1 test was 57% and 87%, respectively, and those of the IgM test was 50% and 84%, respectively. The combined sensitivity and specificity of the SD Dengue Duo(r) NS1/ IgM test was 72% and 80%, respectively. The SD Dengue Duo(r) NS1 test detected NS1 for up to 9 days from onset of fever. Primary and secondary dengue cases were classified according to the IgG test, of which the kit identified 88% and 26% of primary and of secondary infection, respectively. Although the SD Dengue Duo(r) kit was not as accurate as the standard tests, it still can serve the useful reference for initial screening of suspected dengue cases, especially in poor resource hospital settings and aid in clinical disease management of dengue infection. PMID- 26867380 TI - ANTIGENIC AND GENETIC CHARACTERIZATION OF INFLUENZA B VIRUSES IN 2012 FROM SLUMS, DHAKA, BANGLADESH. AB - Nasal and throat swab samples were collected from 400 subjects with influenza like illness during June to September, 2012 from two heavily crowded slums, Rayerbazar and Hazaribagh, situated southeast of Dhaka, Bangladesh. Forty-one samples were positive for influenza B virus using quantitative RT-PCR, but no influenza A virus was detected. Antigenic characterization revealed that the influenza B viruses were of Yamagata and Victoria lineages, which was confirmed from genetic analysis of hemagglutinin (HA) and neuraminidase (NA) genes. Co circulation of influenza B viruses of both Yamagata and Victoria lineages in the slums of Dhaka indicates that introduction of a tetravalent vaccine formulation that includes both of these influenza B virus lineages would be more effective in this population. PMID- 26867381 TI - NOROVIRUS OUTBREAK AT A DAYCARE CENTER IN BANGKOK, 2014. AB - Norovirus is a leading cause of acute non-bacterial gastroenteritis worldwide, affecting developing and developed countries, both children and adults. This study describes an outbreak of acute gastroenteritis at a daycare center of a tertiary level hospital in Bangkok, Thailand during October 2014. Although none of the staff became symptomatic, 8 of 11 children attending the center and 4 of their household contacts developed acute gastroenteritis. No pathogenic bacteria or rotavirus were detected in their evaluation; however, 3 out of 7 stool samples from the cases were positive for norovirus GII.17. Reverse transcriptase polymerase chain reaction analysis with sequence and phylogenetic analysis revealed the viral strain was the same strain reported from Taiwan in 2013. Because norovirus is a frequent cause of outbreaks in crowded conditions, early detection and preventive measures are important to control outbreaks. PMID- 26867382 TI - DETECTION BY DUPLEX RT-COUPLED NESTED PCR OF HEPATITIS A AND ROTAVIRUS IN OYSTERS FROM THAILAND EAST COAST. AB - Abstract. An efficient and rapid virus detection method is required for routine monitoring and risk assessment in food products. A duplex RT-coupled nested PCR method was developed to detect the simultaneous presence of hepatitis A virus (HAV) and rotavirus in commercial oysters from the eastern coast of Thailand. Primers were designed to amplify HAV VP4 and rotavirus VP7 genes. Although excess amounts of target template of one virus type interfered with RT-PCR am- plification of the other, this was overcome by including a nested duplex PCR step. Detection limit for both types of virus of this technique in oyster samples was more than 1,000-fold lower than that of the equivalent monoplex method. Out of 41 oyster samples 63% were positive for either one or both viruses. All rotaviruses belonged to group A G1P[8]. The use of multiplex RT-coupled nested PCR technique provides a cost-effective, rapid, sensitive and efficient tool to detect a wide diversity of viral pathogens and to improve control of virus infection in oysters. PMID- 26867383 TI - MOLECULAR CONFIRMATION OF ENTEROVIRUS FROM SEWAGE AND DRINKING WATER SAMPLES FROM THREE CITIES, PAKISTAN: A POTENTIAL RISK FACTOR FOR PUBLIC HEALTH. AB - Gastroenteritis causes from 4 to 10 million children deaths every year worldwide, mainly from infection with water-borne Enteroviruses, which consist of 67 diverse serogroups. Forty-two sewage and drinking water samples from three metropolitan cities of Pakistan were analyzed for the occurrence of Enterovirus by nested RT PCR amplification. Molecular detection was based on amplification of a part of 5'UTR region of the viruses. Our results revealed an alarming situ- ation in densely populated areas of the three main cities of Pakistan: 28%, 19% and 21% of drinking water samples were positive for enteroviruses in Islamabad, Rawalpindi and Lahore, respectively. Sequence analysis and phylogenetic study of the amplified region of the virus revealed its close relationship with Coxsackie A strains reported from Greece, Singapore and USA. PMID- 26867384 TI - CAUSATIVE AGENTS OF SEVERE COMMUNITY ACQUIRED VIRAL PNEUMONIA AMONG CHILDREN IN EASTERN THAILAND. AB - Pneumonia is a leading cause of morbidity and mortality among infants and young children. The most common causes of pneumonia in children are respiratory viruses. In Thailand, the epidemiology of the viruses causing community-acquired pneumonia (CAP) among children is poorly defined. In this cross sectional study we used nasopharyngeal samples collected from hospitalized children diagnosed with severe CAP in accordance with WHO criteria between June 2013 and May 2014 to determine the causes of infection. The samples were analyzed for respiratory syncytial virus (RSV), parainfluenza viruses (PIV) types 1,2 and 3, adenovirus, rhinovirus, influenza viruses types A and B and coronavirus by polymerase chain reaction (PCR) and reverse transcriptase-polymerase chain reaction (RT-PCR). Of 102 cases of severe CAP, samples were obtained in 91 cases and 48 (52.7%) were positive for respiratory viruses. The most common viruses were RSV (n = 22; 45.8%), rhinovirus (n = 11; 22.9%) and adenovirus (n = 9; 18.7%). Patients were aged 1 month to 4 years 5 months, with a median age of 1 year 1 month. Thirty seven (77.1%) were male. Asthma was the most common co-morbidity affecting 5 (10.4%) of the 48 cases with an identified virus. The peak prevalence occurred during October (n = 17). All patients required oxygen therapy and 17 (35.4%) required mechanical ventilation. The median length of hospitalization was 11 days. Preterm infants had a significantly higher rate of RSV infection than other respiratory viruses (8 of 21; 38% vs 3 of 27; 11.1%) (p = 0.02). Viruses were most commonly associated with severe CAP among children aged less than 1 year. The peak prevalence occurred during the rainy season. Our findings suggest that young and preterm infants with CAP should be monitored closely due to their high risk for developing serious complications. PMID- 26867385 TI - BIOPSY-PROVEN BK VIRUS NEPHROPATHY WITHOUT DETECTABLE BK VIREMIA IN A ONE-YEAR POST-KIDNEY TRANSPLANT RECIPIENT. AB - BK virus nephropathy (BKVN) is an important clinical problem in kidney transplant (KT) recipients. The sequence of disease is usually viruria, viremia and then nephropathy. Diagnosis of BK virus (BKV) infection includes checking BKV DNA in the urine, in the plasma and histology on renal biopsy. This last method is used to diagnose BKVN. We describe a KT patient with BKVN without detectable BK viremia. A 62-year-old female with hypertensive nephropathy underwent renal transplant from a living relative donor in December 2011. Fourteen months after transplantation, her serum creatinine(SCr) rose up from 1.2 to 1.6 mg/dl with biopsy-proven acute antibody-mediated and cellular rejection. After pulse methylprednisolone, plasmapheresis and intravenous immunoglobulin, her SCr decreased to baseline but she subsequently developed cytomegalovirus infection with pancytopenia and transaminitis. The SCr rose to 1.9 mg/dl despite ganciclovir treatment. Renal ultrasound and antegrade pyelogram showed partial obstruction of the proximal ureter with moderate hydronephrosis. A quantitative polymerase chain reaction (PCR) assay for BKV DNA was negative (less than 10 copies/ml). A renal biopsy was performed and the pathology revealed viral cytopathic changes in the tubular epithelium with interstitial inflammation. The renal biopsy also showed BKV nucleic acid sequences by in-situ hybridization confirming BKVN. Immunosuppression regimen was changed to cyclosporine, low-dose prednisolone and leflunomide. A temporary percutaneous nephrostomy was performed. Her renal function improved within one week. The diagnosis of BKVN should be considered in a KT recipient with a rising SCr with or without BK viremia and should be made by renal biopsy. PMID- 26867387 TI - PUBLIC AWARENESS OF HIV/AIDS: HOW MEDIA PLAY A ROLE?. AB - Abstract. This paper examines the effectiveness of media in public awareness of the HIV/AIDS issue among the public in an area in central Selangor, comprising Kuala Lumpur and its surroundings and suburbs in Malaysia. Cross-sectional survey questionnaires were distributed to 384 respondents about accessing the public awareness of modes of HIV transmission, perceptions and attitudes towards people living with HIV/AIDS, as well as people's understanding about government policies to curb HIV/AIDS. Health care practitioners and newspapers were the preferred sources of information seeking on HIV/AIDS among the public. Most of the respondents were aware of the modes of HIV transmission. However, they were some respondents who still have misconceptions about the modes of transmission. Most of the respondents were not aware about the government's significant policies to address HIV/AIDS in the region. Overall, the respondents had certain knowledge about HIV transmission modes and moderate positive perceptions and attitudes towards people living with HIV/AIDS. Future studies should be conducted to examine about who sets the agenda in the media, and apart from gatekeepers, who are the real decision makers in deciding what is important to inform the public. PMID- 26867386 TI - ESTABLISHING MEAN CD4+ T CELL VALUES AMONG HEALTHY JAVANESE ADULTS IN INDONESIA. AB - The objective of this study was to establish mean CD4+ T cell values among healthy Javanese adults in Indonesia. Two hundred forty-one healthy adults (119 women and 122 men), aged 18-65 years, were enrolled in the study. CD4+ T cells were analyzed by immunophenotyping. The mean absolute CD4+ T cell count was 753.3 +/- 270.3 cells/ul (median = 725.0 cells/ul) and the mean CD4+ T cell percentage was 32.6 +/- 7.7%, (median = 31.0%). Women had a slightly higher mean absolute CD4+ T cell count and CD4+ T cell percentage (779.1 +/- 271.0 cells/ ul; 33.4 +/- 8.2%) than men (728.2 +/- 268.3 cells/ul; 31.8 +/- 7.1%), but the differences were not statistically significant (p = 0.126, p = 0.216, respectively). The mean absolute CD4+ T cell varied significantly by age group (p = 0.002). Sixty-one point seven percent of men studied (37/60) had a CD4+ T cell count less than 500 cells/ul (OR 1.8; 95% CI = 1.001-3.300). Absolute CD4+ T cell counts among Javanese Indonesians varied significantly by age. PMID- 26867388 TI - CHARACTERISTICS AND FACTORS INFLUENCING UNPROTECTED ANAL INTERCOURSE AMONG MEN WHO HAVE SEX WITH MEN IN FUYANG, CHINA. AB - Men who have sex with men (MSM) are at risk for contracting hu- man immunodeficiency virus (HIV) infection. The objective of this study was to explore the characteristics and factors influencing unprotected anal intercourse (UAI) among MSM in Fuyang, China in order to develop an intervention program to prevent the spread of HIV infection among MSM. We conducted this cross sectional study among 413 MSM in 2013. Participants completed an interviewer- administered questionnaire and were tested for HIV and syphilis infections. Three hundred fifty of 413 subjects reported sexual activity with a male partner during the previous 6 months; of these 27(7.7%) had unprotected sex. Forty-four subjects had sex with a female partner during the previous 6 months; of these 25 (58.1%) had unprotected sex. The frequency of having unprotected sex with a female was significantly greater than with a male (chi2 = 84.52, p < 0.001). Multivariate logistic analysis showed education level (OR = 0.45, p = 0.003), length of time of current residence (OR = 0.47, p = 0.014), knowledge about HIV infection (OR = 0.09, p = 0.022) and integrated interventions (OR = 0.32, p < 0.001) were all significantly associated with UAI. High-risk sex behavior was common among the study population. A targeted interventions needs to be developed urgently. PMID- 26867389 TI - FACTORS ASSOCIATED WITH DELAY IN TUBERCULOSIS TREATMENT AT 10 TERTIARY LEVEL CARE HOSPITALS IN THAILAND. AB - Tuberculosis (TB) is common in Thailand. Delay in initiating tuberculosis treatment is a major public health problem. Delay in treatment can result in more severe diseases, risk for death, and greater risk of tuberculosis transmission in the community. We attempted to determine the duration from onset of TB symptoms to the date of first consultation (patient delay) and the factors associated with that delay at 10 tertiary level care hospitals in Thailand. All participants aged 18 years who were willing to participate were included in the study, which was conducted from January to December 2012. A structured questionnaire and medical records were used to collect data. One hundred ninety-nine TB patients were included in the study. The mean age of subjects was 48 years (SD = 15.9); 69.8% were male. The median duration from onset of symptoms to first medical consultation was 30 days. On multivariate analysis, living in an urban area (adjusted odds ratio = 2.81; 95% CI: 1.29-6.14) was an independent risk factor for the delay. Delay in seeking help is a common problem among TB patients in Thailand. At risk populations need to be educated on the importance of presenting for early medical consultation if they have symptoms of TB. PMID- 26867390 TI - PREVALENCE AND FACTORS ASSOCIATED WITH MULTIDRUG-RESISTANT TUBERCULOSIS AT SIRIRAJ HOSPITAL, BANGKOK, THAILAND. AB - The objective of this study was to determine the prevalence and factors associated with multidrug-resistant tuberculosis (MDR-TB) at Siriraj Hospital, Bangkok, Thailand. We conducted a retrospective unmatched case-control study of patients clinically diagnosed and microbiologically confirmed to have tuber- culosis (TB) at Siriraj Hospital from 2010 to 2012. Patient characteristics, clinical data, microbiological findings, outcomes and drug susceptibilities were recorded. A total of 188 subjects were included in the study; 52.1% (98) were males; the mean age was 48.9 years. Subjects were categorized into one of two groups, as follows: non-MDR-TB (141 patients) and MDR-TB (47 patients). The prevalence of MDR- TB was 2.6%. Co-morbidities of study subjects included diabetes mellitus (16.5%), HIV infection (16%) and cancer (5.9%). One hundred thirty-one patients (69.7%) had pulmonary TB. Factors significantly associated with MDR-TB were age < 65 years (OR = 6.94; 95% CI: 1.02-45.49; p = 0.048), history of TB (OR = 51.86; 95% CI: 12.35-217.79; p < 0.001), HIV co-infection (OR = 3.83; 95% CI: 1.02-14.38; p = 0.047) and alcohol consumption (OR = 3.90; 95% CI: 1.03-14.72; p = 0.045). Of the 146 patients for whom a clinical outcome was available, 51 (34.9%) had an unfavorable outcome. Poor compliance (OR = 13.51; 95% CI: 3.97-45.45; p < 0.001) and previous history of TB (OR = 8.16; 95% CI: 1.76-37.73; p = 0.007) were associated with an unfavorable outcome. MDR-TB was significantly associated with: patients aged < 65 years, those with a previous history of TB, those with HIV co-infection and those who drank alcohol. These factors should be kept in mind when treating TB patients at Siriraj Hospital, Thailand. PMID- 26867391 TI - DISSEMINATION OF SALMONELLA ENTERICA SEQUENCE TYPES AMONG ASEAN ECONOMIC COMMUNITY COUNTRIES. AB - Food-borne illness caused by Salmonella enterica remains a public health problem and results in economic loss worldwide. With the up-coming establish- ment of the ASEAN Economic Community (AEC) allowing unrestricted move- ment of labor and goods, there is a higher risk of pathogen transmission among the AEC countries. This study characterized and investigated the spatial and temporal associations of S. enterica strains isolated in AEC countries during 1940- 2012 compared with those isolated in northern-Thailand during 2011-2013. Of the 173 S. enterica strains examined, 68 sequence types (STs) and 32 clonal complexes (CCs) were identified by multi loci sequence typing. Twenty-one strains belonged to four sequence types new to AEC countries, and they constituted only two CCs. A number of strains originated from various countries with multiple hosts, were highlighted. There was evidence of strains circulating in the AEC region well over a decade. Such information will be important in formulating biosecurity measures, as well as in educating regarding the risk of disease transmission in AEC. PMID- 26867392 TI - BACTERIAL IDENTIFICATION USING SSRA ENCODING TRANSFER-MESSENGER RNA. AB - Abstract. Ribosomal DNA (rDNA) sequences are widely used for phylogenetic and bacterial identification. However, rDNA of different species often reveals similar or identical same sequences. This study employed the bacterial stable small RNA (ssrA) gene encoding transfer-messenger RNA (tmRNA) as a tool for identification of Staphylococcus aureus, Enterococcus spp, Pseudomonas spp and Enterobacteriaceae from clinical isolates as representative groups using PCR and species specific primers. The method correctly identified 11 standard strains and 99 clinical isolates. Quantitative PCR revealed a limit of detection of 10(-5) ug of DNA for S. aureus and Enterococcus spp, and 10(-6) ug for Pseudomonas spp and Enterobacteriaceae. Further studies with a greater number of bacteria especially from clinical samples will need to be undertaken before this bacterial molecular marker can be applied in a clinical setting. PMID- 26867393 TI - THE BURDEN OF INVASIVE NEONATAL GROUP B STREPTOCOCCAL (GBS) DISEASE IN THAILAND AND THE PHILIPPINES. AB - Group B Streptococcus (GBS) is a leading cause of meningitis and sepsis in infancy, but burden of disease data are scarce for Asia. We performed two hospital-based, prospective, descriptive, observational studies using similar protocols in the Philippines and Thailand to evaluate neonatal GBS disease epidemiology. Infants aged <90 days with a GBS-positive culture from normally sterile sites using routine microbiological standards were eligible for inclusion. Awareness of GBS symptoms was raised by informing all women at delivery and follow-up for 90 days post-delivery. Infections were classified as early onset disease (EOD) if they occurred within 6 days of birth and late Onset disease (LOD) if they occurred 7-89 days after birth. Due to ethical requirements in Thailand, consent for study participation, including periodic post-discharge telephone calls, was obtained at delivery. Parents in the Philippines gave consent for study participation at case identification. The clinical outcomes of GBS infections were recorded. During the 6-month study period, two cases (one fatal) of EOD were identified among 8,409 live births at the study hospitals in Thailand and three cases (two fatal) of EOD were identified among 11,768 live births reported at the study hospitals in the Philippines. Incidence rates per 1,000 live births were 0.2 (95% CI: 0.0-0.8) and 0.3 (95% CI: 0.1-0.8) in Thailand and the Philippines, respectively. There were no cases of reported LOD. The low number of cases precluded analysis of serotype distribution and case fatality rates. Large epidemiological studies are needed to better understand the factors influencing GBS infection incidence in Asia. PMID- 26867394 TI - HISTOPLASMOSIS MYOSITIS: A CASE REPORT AND LITERATURE REVIEW. AB - Disseminated histoplasmosis is an AIDS-defining illness that can affect multiple organ systems. Myositis due to histoplasmosis is rare in HIV infected patients. We report here an HIV-infected patient who presented with myositis caused by Histoplasma capsulatum. Her HIV was under poor control and her CD4 cell count was only 11 cells/mm3. She responded well to treatment but later succumbed to another opportunistic infection. The literature on disseminated histoplasmosis is reviewed. PMID- 26867395 TI - SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN. AB - Haemophilus influenzae type b (Hib) is a major cause of meningitis and pneumonia with high morbidity and mortality rates in young children. The introduction of effective and well-tolerated conjugate Hib vaccines, has nearly eradicated this disease in many countries. We investigated the safety of the Hib PRP-CRM197 vaccine in a multi-center post-marketing surveillance (PMS) study. Korean children (N = 764) aged 1-33 months were enrolled when receiving a routine primary immunization or a booster vaccine with Hib PRP-CRM197 and solicited and unsolicited adverse events (AEs) were recorded using a diary card for 7 and 28 days after each vaccination, respectively. In this study, AEs were reported by 66% of subjects but were generally mild, with 42% of subjects reporting solicited AEs and 46% reporting unsolicited AEs. Among the unsolicited AEs, 98% were determined to be unrelated to the study vaccine. The studied Hib PRP-CRM197 vaccine was well tolerated by the study group and found to have a similar safety profile to that reported in other clinical studies. This vaccine is suitable for routine immunization against Hib disease among Korean children. AEs due to this vaccine will continue to be monitored. PMID- 26867396 TI - IMMUNOGENICITY AND SAFETY OF QUINVAXEM(r) (DIPHTHERIA, TETANUS, WHOLE-CELL PERTUSSIS, HEPATITIS B AND HAEMOPHILUS INFLUENZAE TYPE B VACCINE) GIVEN TO VIETNAMESE INFANTS AT 2 TO 4 MONTHS OF AGE. AB - Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem(r) vaccine in children. A total of 131 infants received the Quinvaxem(r) vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP >= 0.15 ug/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP >= 0.15 ug/ml). The Quinvaxem(r) vaccine was well tolerated and has a low rate of adverse events. Quinvaxem(r) given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam. PMID- 26867397 TI - ADVERSE EVENTS POST-DTAP AND DTwP VACCINATION IN THAI CHILDREN. AB - We conducted a prospective study to compare the development of fever (axillary T >= 37.9 degrees C) within 4 hours of vaccination, determine the proportion of children who develop high fever (T >= 39 degrees C) and evaluate parental days missed from work due to their children's vaccination with either the diphtheria tetanus-whole cell pertussis (DTwP) or diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The results of this study can help physicians and parents decide whether to have their child vaccinated with the DTwP or more expensive DTaP vaccine. We studied 140 healthy Thai children aged 2 months to 6 years from December 2011 to March 2012 who presented for vaccination. Parents recorded their child's temperature, local and systemic adverse reactions and missed days from work due to these adverse events on a diary card. Of the 140 participants, 72 received the DTwP vaccine and 68 received the DTaP vaccine. The median (IQR) age was 4 (2-6) months and the median weight was 7.1 (5.6-8.7) kg. Twenty children developed fever (axillary T >= 37.9 degrees C) within 4 hours following vaccination, 17 (23.6%) had received the DTwP vaccine and 3 (4.4%) had received the DTaP vaccine (p = 0.040). One child (1.4%) who had received the DTwP vaccine and none who received the DTaP vaccine developed high fever (T >= 39 degrees C) within 4 hours of vaccination (p = 0.329). Parents of two children who received the DTwP vaccine and one child who received the DTaP vaccine missed work following vaccination (p = 0.059). In conclusion, children who received the DTwP vaccines were more likely to have early post-vaccination fever and higher fever but there was no significant difference between the two groups in parental days lost from work. PMID- 26867398 TI - AN INCREASE IN RISK FACTORS FOR CARDIOVASCULAR DISEASE IN YOGYAKARTA, INDONESIA: A COMPARISON OF TWO CROSS-SECTIONAL SURVEYS. AB - This paper aims to describe changes in risk factors for cardiovascular disease (CVD) over a five year period in urban Indonesia. In 2004 (n = 3,205) and 2009 (n = 2,467) we conducted cross-sectional surveys of residents in Yogjakarta City, Indonesia evaluating risk factors for CVD. Smoking habits, fruit and vegetable intake, physical activity, blood pressure, weight, and height were recorded. The results of these 2 surveys conducted 5 years apart were then compared. The risk for having a CVD event was also calculated. Behavioral CVD risk factors were more common among men. The predicted risk of having a CVD event increased from 8.4% to 11.3% among men between 2004 and 2009. Effective measures need to be taken to change these behaviors among men in Yogyakarta, Indonesia. PMID- 26867399 TI - DENTAL CARIES AND RELATED ORAL HEALTH FACTORS AMONG 9 TO 18 MONTH OLD THAI CHILDREN. AB - Dental caries can occur as soon as the first tooth erupts. We studied the caries prevalence and related risk factors among children aged 9-18 months in U Thong District, Suphan Buri Province, Thailand. A total of 151 children, whose primary caregivers were willing to participate in this study, were evaluated for decayed, missing, and filled tooth surfaces (dmfs). Questionnaires were given to the primary caregivers of the study subjects to ascertain their socio-economic status, oral hygiene habits, and child-feeding habits. The Mann-Whitney U and Kruskal-Wallis tests were used to evaluate bivariate outcome data. Hierarchical multiple regression analysis was used to determine variables predictive of dental caries in the studied children. The prevalence of dental caries among the 151 subjects was 32.5%; 15.9% had at least one cavity (cavitated caries) and 16.6% had white lesions (non-cavitated caries). The mean dmfs score was 2.83 +/- 6.48. Significant associations were seen between the dmfs score and the number of erupted teeth (p < 0.001) and toothpaste usage (p < 0.01). Hierarchical multiple regression analysis revealed four factors significantly associated with caries: number of erupted teeth, which had the highest Beta value (P = 0.35, p < 0.01), nighttime bottle feeding (P = 0.17, p < 0.05), frequency of drinking sweetened milk (P = 0.17-0.18, p < 0.05) and falling asleep with a bottle in the mouth (P = 0.18, p < 0.05). Nighttime bottle feeding, frequency of drinking sweetened milk and falling asleep with a bottle in the mouth were important caries risk factors and the number of erupted teeth was a strong caries risk predictor. Dentists should educate caregivers about these risk factors. PMID- 26867400 TI - OCCUPATIONAL CARBAMATE POISONING IN THAILAND. AB - Carbamate insecticide is a leading cause of poisoning in Thailand. The objective of this study was to characterize the clinical manifestations and modes of occupational exposure in carbamate poisoning cases. We retrospectively studied all the cases of carbamate poisoning due to occupational exposure recorded in the Ramathibodi Poison Center Toxic Exposure Surveillance system during 2005 to 2010. Demographic data, clinical manifestations and severity were analyzed statistically. During the study period, 3,183 cases were identified, of which 170 (5.3%) were deemed to be due to occupational exposure. Ninety-six cases (56.5%) and 35 cases (20.6%) were poisoned by carbofuran and methomyl, respectively. Carbofuran is sold as a 3% grain and applied by sowing; methomyl is sold as a liquid and is applied by spraying. The majority of poisoned patients did not wear personal protective equipment (PPE) while applying the carbamates. The clinical manifestations of occupational carbofuran poisoning recorded were nausea and vomiting (82.3%), headaches (56.3%) and miosis (19.8%). The clinical manifestations of methomyl poisoning were nausea and vomiting (74.3%), headaches (57.1%) and palpitations (11.4%). Most patients in both groups had mild symptoms. Only one case in each group required endotracheal intubation and mechanical ventilation support. There were no deaths and the lengths of hospitalization ranged from 2 hours to 2 days. Occupational carbamate poisoning cases in our series were mostly mild and the patients recovered quickly. There were only rare cases of serious symptoms. Lack of knowledge and inadequate PPE were the major factors contributing to occupational poisoning. Educating agricultural workers about correct precautions and pesticide use could minimize this type of poisoning. PMID- 26867401 TI - FACTORS RELATED TO MOTORCYCLE ACCIDENT RISK BEHAVIOR AMONG UNIVERSITY STUDENTS IN NORTHEASTERN THAILAND. AB - Young motorcycle drivers in Thailand are at high risk for road traffic accidents. We conducted this study to identify factors associated with motorcycle accident risk behavior (MARB). We studied 372 randomly selected university students aged 18-22 years (mean 20.2 years; women comprised 68.0% of our participants), who attend a government university in northeastern Thailand. Each student was asked to fill out a questionnaire asking about MARB and factors associated with this behavior. The respondents had an average of 6.2 years (SD+3.09) motorcycle driving experience, 72.3% had a motorcycle driver's license and 83.0% had accident insurance. The prevalence of self-reported motorcycle accident injuries was 42.7%. Their major MARB were using a telephone while driving (69.3%), speeding (45.4%), driving with more than one passenger (40.1%), drunk driving (22.1%), and not wearing a helmet (23.3%). Factors related to MARB were: gender, with men engaged in risky behavior more often than women (p < 0.05); duration of motorcycle driving--drivers with > 5 years experience were more likely to engage in risky behavior (p < 0.05); and knowledge of safe driving, those with a greater knowledge of safe driving were more likely to drive safely (p < 0.001). Having a greater awareness of MARB was associated with lower risk of engaging in risky behavior (p < 0.001). Students who engaged in risky behavior were more likely to view it as normal behavior (p < 0.001) and less likely to have adequate self control (p < 0.001). Our findings indicate a need to strengthen accident prevention programs for university students in northeastern Thailand. PMID- 26867402 TI - Editorial. PMID- 26867403 TI - Accessing the online archive for the Journal of the Royal Naval Medical Service. AB - Following work by the editorial team, notably Surg Lt Cdr M O'Shea, and with funding from the Wellcome Trust, every edition of this Journal dating back to the first edition in 1915 is available on our website. This article gives details of how to access it. PMID- 26867404 TI - Maritime in transit care. AB - Operation GRITROCK saw the first operational deployment of the Maritime In Transit Care team from the Role 2 (Enhanced) (R2(E)) Medical Treatment Facility, which is able to provide Damage Control Surgery and the limited holding of patients, situated on board RFA ARGUS. Whilst the Medical Emergency Response Team demonstrated the capability of advanced military Pre-Hospital Emergency Care (PHEC) on Op HERRICK, the need to provide a similar high level of care on contingency operations was recognised. Op GRITROCK allowed for the continued exploration of a maritime capability from an established R2(E) platform whilst providing medical evacuation capability for a significant population at risk distributed over a large Joint Operation Area. Although the patient load during the operation was low, key lessons were learnt and opportunities identified to further develop the newly recognised sub-speciality of PHEC, both medically and logistically, and these will be discussed in this article. PMID- 26867405 TI - The operational role of the Royal Marines Band Service during the contingency era: lessons from Op GRITROCK. AB - The Royal Marines Band Service (RMBS) deploys in support of the Royal Naval Medical Service in a variety of operational roles. This article describes the roles that RMBS personnel performed whilst deployed on board RFA ARGUS during the recent Operation GRITROCK. The article is divided into five main sections, each describing one aspect of the work that RMBS ranks were asked to undertake: casualty handling; working within Primary Casualty Receiving Facility (PCRF) departments; personal protective equipment (PPE) monitoring and drills; temperature monitoring; and last, but not least, musical support. This will provide the reader with an insight into what the RMBS have achieved whilst deployed on board ARGUS and also what skills they are able to bring, both to contingency operations and operations in the medical environment. PMID- 26867406 TI - Devising a training programme and reviewing the lessons identified during contingency operations on board the Role 3 Maritime platform. AB - The deployment of the Primary Casualty Receiving Facility (PCRF) to Sierra Leone in October 2014 in support of Operation GRITROCK was a contingency operation that required a very specific training programme. This article discusses the training and how it evolved beyond its original remit into a programme used as a management tool to meet the needs of the staff. The result was the implementation of a comprehensive package from which lessons can be drawn and used when planning future operations. PMID- 26867407 TI - PCRF Pathology, OP GRITROCK--A biomedical scientist's perspective. AB - The Primary Casualty Receiving Facility (PCRF) Pathology Department was deployed on Operation GRITROCK from October 2014 to April 2015 to support the medical treatment facility on RFA ARGUS. The department deployed with enhanced microbiology capability and effectively became the microbiology reference laboratory for the Joint Operations Area (JOA). A platelet apheresis capability was delivered in the maritime environment for the first time on an active operation. PMID- 26867408 TI - Platelet apheresis in a deployed maritime environment: experiences from Operation GRITROCK. AB - When the Primary Casualty Receiving Facility (PCRF) on Royal Fleet Auxiliary (RFA) ARGUS deployed to Operation GRITROCK in October 2014, platelet apheresis had yet to be proven as a sustainable and usable capability for improving provision of blood products on a maritime platform. This paper explores the difficulties encountered by nurses tasked with setting up this capability once deployed and the requirements needed to ensure that this capability is maintained for future operations. PMID- 26867409 TI - Medical supply on contingency military operations: experience from Operation GRITROCK. AB - Medical supply during military operations has the ability to affect the efficacy of the operation being undertaken, either negatively or positively. An appropriately-managed maritime platform with a robust medical supply chain during transit and on arrival in theatre is the main aim. A secure supply chain will reduce any implications that logistics may have with regard to capability, and negate the effects of deficiencies of short shelf life items occurring over time and during use in high tempo operations. PMID- 26867410 TI - From RAF to RN--the transition from Princess Mary's RAF Nursing Service (PMRAFNS) to Queen Alexandra's Royal Naval Nursing Service (QARNNS). AB - I transferred from the Royal Air Force to the Royal Navy (RN) on 10 July 2014. I would like to share my experiences as a junior RN Officer during Op GRITROCK, looking at some of the similarities and differences between the two Services and their deployed environments: maritime and air. PMID- 26867412 TI - A practical guide to expedition medical planning. AB - Expedition medical planning is integral in ensuring participant safety and maximising the likelihood of achieving the expedition aims. The task of producing a medical plan will often fall to a medical officer of limited experience. The aim of this article is to provide a concise, practical guide to aid junior medical officers (MOs) in forming a robust and pragmatic medical plan. PMID- 26867411 TI - Nurse-delivered focused echocardiography to determine intravascular volume status in a deployed maritime critical care unit. AB - Focused echocardiography is increasingly used by clinicians to guide fluid resuscitation. The UK Defence Medical Services (DMS) have adopted focused echocardiography as a tool to guide flow assessment and resuscitation in deployed critical care. We aimed to explore whether two focused echo techniques, namely Inferior Vena Cava (IVC) and Left Ventricular Outflow Tract Velocity Time integer (LVOT VTi) respiratory variability could be taught to a group of critical care nurses without previous exposure to ultrasound imaging. After a five-week program of training, validation was carried out on healthy volunteers. The mentor, an accredited focused echo trainer, and six nurses performed a total of forty-eight scans on eleven volunteers. The mentor and students acquired subcostal long axis views of the IVC and apical five chamber views using a high frequency linear ultrasound probe. Mean values from three measurements were obtained for IVC diameter and LVOT VTi. Minimum and maximum values were recorded for both variables across a full respiratory cycle. Echo images were saved and at least two images for each student were reviewed offline by an accredited echo-training supervisor. In all cases students were able to obtain adequate echo windows. There was good correlation between values recorded by the mentor and students for both IVC diameter (r = 0.90, p < 0.001) and LVOT VTi (r = 0.77, p < 0.001). Bland Altman analysis showed good correlation with minimal bias for VTi measurements. There was some increase in bias for IVC measurements below 1.2 cm. In summary, we found that these skills for assessing intravascular volume status could be acquired in a relatively short time by specialist nurses without previous experience, and that results were comparable to those produced by an experienced practitioner. PMID- 26867414 TI - Exercise HIMALAYAN SERPENT: feedback article. AB - Exercise HIMALAYAN SERPENT was open to junior doctors from the United Kingdom (UK) Armed Forces and aimed to educate potential expedition doctors on aspects of high altitude and wilderness medicine as well as conducting adventurous training (AT) and medical research. This was the first time such an exercise had been undertaken and this article explores the views of those junior doctors taking part to assess whether the exercise met the aims and objectives it set out. PMID- 26867413 TI - Medical reconnaissance for the Defence Medical Services Dhaulagiri Expedition 2016. AB - The formation of a clear and well-informed medical plan is critical to the safe planning and execution of any expedition in remote locations. We performed a reconnaissance of medical facilities in Nepal in March 2015 prior to a large Defence Medical Services (DMS) expedition to the Dhaulagiri area in 2016. Visiting relevant medical facilities in person provides invaluable information and experience of what healthcare services may be relied upon in managing an expedition casualty, in scenarios ranging from minor illness to major trauma. We describe the principles, practice and level of detail required for performing such a medical reconnaissance and illustrate this with examples of our findings from Nepal. PMID- 26867415 TI - Lessons learned while undertaking high altitude medical research in the Himalayas. AB - Undertaking medical research during military adventurous training expeditions presents a unique set of challenges to medical personnel, and for those considering doing so in the future the task may seem daunting. This article details some of the challenges faced whilst undertaking high altitude research on a recent Defence Medical Services (DMS) adventurous training expedition to the Dhaulagiri circuit in Nepal. By discussing what led to some of the problems encountered, how they were overcome, and in some instances how they could have been avoided in the first place, it is hoped that the article will act as a guide for others who plan on undertaking future research in a similar environment. PMID- 26867416 TI - A systematic review of the use of tourniquets and topical haemostatic agents in conflicts in Afghanistan and Iraq. AB - INTRODUCTION: The recent conflicts in Afghanistan and Iraq have seen increased use of tourniquets and topical haemostatic agents in the management of battlefield trauma. The aim of this paper is to review the available evidence for their efficacy and continued use. METHODS: A systematic review of the medical literature published as a consequence of conflicts in Iraq in Afghanistan was conducted to determine the clinical outcomes from the use of tourniquets and haemostatic agents for haemorrhage control in limb extremity injury. RESULTS: Studies were retrospective cohort or prospective observational studies by design. None were eligible for meta-analysis and control groups were rarely available for ethical reasons. Despite methodological limitations, tourniquets were shown to save lives if applied prior to the onset of shock or in a pre-hospital setting. Topical haemostatic agents were shown to be useful adjuncts in haemorrhage control with small numbers of complications. CONCLUSION: In the military setting, tourniquet use in extremity trauma improves survival when used prior to the onset of shock. Topical haemostatic agents provide additional means of haemorrhage control, though further studies to identify the most effective types are necessary. Adequate training and protocols for use must be implemented to prevent complications through use. PMID- 26867417 TI - What do we need for airway management of adult casualties on the Primary Casualty Receiving Facility? A review of airway management on Role 3 Afloat. AB - The Primary Casualty Receiving Facility (PCRF) of the Royal Navy (RN) is currently based on Royal Fleet Auxiliary (RFA) ARGUS and provides a functioning hospital with surgical teams and a CT scanner (Role 3) within the maritime environment. The case mix could include complex trauma, critically ill patients returning to theatre several times, as well as non-battle injury procedures. This paper describes how we have used national guidelines, evidence from recent military experience, and the Clinical Guidelines for Operations (CGOs) to review and rationalise the airway equipment that is available and that would be required for the PCRF in its current configuration, whilst maintaining capability in a deployed setting. PMID- 26867418 TI - The management of unexplained collapse in service age personnel. AB - Unexplained collapse is a common presentation to medical practitioners, with a wide range of differential diagnoses making assessment problematic. Without a methodical approach to the patient presenting with unexplained collapse, potentially life-threatening conditions may not be recognised, whilst benign presentations can be over-investigated. This article will review the assessment, differential diagnosis and management of unexplained collapse, whilst considering the impact in the military environment. PMID- 26867419 TI - The management of acute seizures in Naval Service personnel. AB - Seizures are a relatively common Emergency Department (ED) presentation among young adult populations, considered for the purpose of this report as being aged 15-59. Due to the varied aetiologies involved, understanding of the potential causes and their presentation is key to managing these patients. Although seizure incidence within the United Kingdom (UK) Armed Forces population is generally low, it is not negligible. Therefore, awareness of the initial management is required by all those involved in patient care from the Medical Assistant (MA) at the Role 1 facility, through to the senior doctors at Role 3 establishments. All management should be in line with the Clinical Guidelines for Operations (CGOs) and Advanced Life Support (ALS) principles, with resuscitation, seizure control and patient stabilisation taking precedence initially. Ultimately, the use of laboratory testing and imaging at a Role 3 setting will be required to accurately confirm a diagnosis. Information obtained during these assessments may serve to assist the Naval Service Medical Board of Survey (NSMBOS) in determining suitability for continued Service retention and employment. PMID- 26867420 TI - Abdominal hernias: a clinical review of their assessment and management in the Naval Service. AB - Hernias are a relatively common occurrence in the armed forces community and may affect an individual's fitness for duty and impact on operational capability, particularly in specialist occupations. Their early identification and management will allow appropriate treatment and minimise any impact on operational capability. This article aims to summarise the assessment and management of simple hernias and considers occupational considerations in their management for personnel serving in the Royal Navy and Royal Marines. PMID- 26867421 TI - Lower limb stress fractures in military training. AB - This article describes stress fractures that are seen in military training, and reviews the relevant literature. The information is vital for medical personnel who work with the United Kingdom (UK) Armed Forces, particularly those working in training establishments. The author suggests areas for further research and discusses some of the issues in current UK Armed Forces training. PMID- 26867422 TI - Recent changes in hypoxia training at the Royal Air Force Centre of Aviation Medicine. AB - Hypoxia training at the Royal Air Force Centre of Aviation Medicine (RAF CAM) has traditionally involved the use of a hypobaric chamber to induce hypoxia. While giving the student experience of both hypoxia and decompression, hypobaric chamber training is not without risks such as decompression sickness and barotrauma. This article describes the new system for hypoxia training known as Scenario-Based Hypoxia Training (SBHT), which involves the subject sitting in an aircraft simulator and wearing a mask linked by hose to a Reduced Oxygen Breathing Device (ROBD). The occupational requirements to be declared fit for this new training method are also discussed. PMID- 26867423 TI - A brown dog tick (Rhipicephalus sanguineus) bite at sea. AB - Medical Officers (MOs) and Medical Branch Ratings (MBRs) must maintain an awareness of the risk of vector-borne diseases among deployed personnel. Personnel working in the maritime environment may not expect to be at risk of tick bites, as ticks typically occupy habitats with dense vegetation such as forests or scrub land. However, tick-borne pathogens can cause serious and sometimes fatal disease, and therefore the risk of tick bites and associated diseases should be recognised. We present a case of a tick bite in a member of a ship's company eight days after leaving port. The tick was identified as a brown dog tick (Rhipicephalus sanguineus), a species known to thrive indoors. We describe several important tick-borne diseases which can be transmitted by R. sanguineus and explore best practice for tick removal and aftercare. Finally, we outline the appropriate management of suspected tick-borne disease in deployed personnel in the maritime environment. PMID- 26867424 TI - Military Health Systems Research Symposium 2015. PMID- 26867425 TI - Report from Association of Surgeons in Training Conference. PMID- 26867426 TI - Obituaries. Surgeon Commander Herbert Ellis. PMID- 26867427 TI - The Eighth Charles Bernard Lecture. PMID- 26867428 TI - Multicolored, Low-Power, Flexible Electrochromic Devices Based on Ion Gels. AB - Ion gels composed of a copolymer and a room temperature ionic liquid are versatile solid-state electrolytes with excellent features including high ionic conductivity, nonvolatility, easily tunable mechanical properties, good flexibility and solution processability. Ion gels can be functionalized by incorporating redox-active species such as electrochemiluminescent (ECL) luminophores or electrochromic (EC) dyes. Here, we enhance the functionality of EC gels for realizing multicolored EC devices (ECDs), either by controlling the chemical equilibrium between a monomer and dimer of a colored EC species, or by modifying the molecular structures of the EC species. All devices in this work are conveniently fabricated by a "cut-and-stick" strategy, and require very low power for maintaining the colored state [i.e., 90 MUW/cm(2) (113 MUA/cm(2) at 0.8 V) for blue, 4 MUW/cm(2) (10 MUA/cm(2) at -0.4 V) for green, and 32 MUW/cm(2) (79 MUA/cm(2) at -0.4 V) for red ECD]. We also successfully demonstrate a patterned, multicolored, flexible ECD on plastic. Overall, these results suggest that gel-based ECDs have significant potential as low power displays in printed electronics powered by thin-film batteries. PMID- 26867429 TI - Screening for perinatal depression: a missed opportunity. PMID- 26867430 TI - Ending the death penalty for juveniles. PMID- 26867431 TI - Acute myocardial infarction in women. PMID- 26867432 TI - Brain health: widening the scope of NCDs. PMID- 26867433 TI - Rheumatology--a call for papers. PMID- 26867436 TI - Strangers when we meet: David Bowie, mortality, and metamorphosis. PMID- 26867437 TI - Roderick Norman McIver MacSween. PMID- 26867438 TI - Should doctors strike? PMID- 26867439 TI - Men B: lack of coverage or vaccine failure? PMID- 26867440 TI - Should doctors strike? PMID- 26867441 TI - Call to duty revisited. PMID- 26867442 TI - Bacterial neonatal sepsis and antibiotic resistance in low-income countries. PMID- 26867443 TI - Closure of abdominal midline incisions: STITCH trial. PMID- 26867444 TI - Closure of abdominal midline incisions: STITCH trial. PMID- 26867445 TI - Closure of abdominal midline incisions: STITCH trial--Authors' reply. PMID- 26867446 TI - Closure of abdominal midline incisions: STITCH trial. PMID- 26867447 TI - Department of Error. PMID- 26867448 TI - Department of Error. PMID- 26867449 TI - Sign of the times: be careful what you say in the operating room. PMID- 26867450 TI - Poncet's disease: unusual presentation of a common disease. PMID- 26867451 TI - Tuberculosis and Poncet's disease: the many faces of an old enemy. PMID- 26867453 TI - Guinea worm disease nears eradication. PMID- 26867454 TI - Treatment of visceral leishmaniasis: options and choice. PMID- 26867455 TI - Plasmid-mediated colistin resistance mechanisms: is it time to revise our approach to selective digestive decontamination? PMID- 26867456 TI - Changing hepatitis B virus epidemiology in rural China. PMID- 26867457 TI - Changing hepatitis B virus epidemiology in rural China. PMID- 26867458 TI - Changing hepatitis B virus epidemiology in rural China - Authors' reply. PMID- 26867459 TI - Respiratory co-morbidities in people with HIV. PMID- 26867460 TI - Ethiopia shows it is single-minded in tackling disease. PMID- 26867461 TI - WHO estimates suggest large herpes simplex virus burden. PMID- 26867462 TI - Infection disease surveillance update. PMID- 26867464 TI - The transmission of Mycobacterium tuberculosis in high burden settings. AB - Unacceptable levels of Mycobacterium tuberculosis transmission are noted in high burden settings and a renewed focus on reducing person-to-person transmission in these communities is needed. We review recent developments in the understanding of airborne transmission. We outline approaches to measure transmission in populations and trials and describe the Wells-Riley equation, which is used to estimate transmission risk in indoor spaces. Present research priorities include the identification of effective strategies for tuberculosis infection control, improved understanding of where transmission occurs and the transmissibility of drug-resistant strains, and estimates of the effect of HIV and antiretroviral therapy on transmission dynamics. When research is planned and interventions are designed to interrupt transmission, resource constraints that are common in high burden settings-including shortages of health-care workers-must be considered. PMID- 26867465 TI - Chronic skin ulcers in a patient returning from Mexico. PMID- 26867466 TI - Adrenal imaging for adenoma characterization: imaging features, diagnostic accuracies and differential diagnoses. AB - Adrenocortical adenoma is the most common adrenal tumour. This lesion is frequently encountered on cross-sectional imaging that has been performed for unrelated reasons. Adrenal adenoma manifests various imaging features on CT, MRI and positron emission tomography/CT. The learning objectives of this review are to describe the imaging findings of adrenocortical adenoma, to compare the sensitivities of different imaging modalities for adenoma characterization and to introduce differential diagnoses. PMID- 26867467 TI - [Carcinomatous meningitis: The radiation therapist's point of view]. AB - Carcinomatous meningitis complicates 5 to 10% of cancers, essentially with breast cancers, lung cancers and melanomas. The incidence probably increased because of therapeutic advances in oncology. Treatment is based on external beam radiotherapy, systemic treatment, intrathecal chemotherapy and supportive care. The aim of this work was to review data on external radiation therapy and carcinomatous meningitis. There are few evidences on the subject, but it is a major topic of interest. A whole brain radiation therapy is indicated in case of brain metastases or clinical encephalitis. Focal radiation therapy is recommended on symptomatic, bulky or obstructive sites. The dose depends on performance status (20 to 40 Gy in five to 20 fractions), volume to treat and available techniques (classic fractionation or hypofractionation via stereotactic radiosurgery). The objective of radiation therapy is to improve quality of life. Association with systemic therapy improves overall survival. Administration of sequential intrathecal chemotherapy may also improve overall survival, but induces more toxicity. The use of new radiotherapy techniques and development of radiosensitizing molecules in patients with good performance status could improve survival in this frequent complication of cancer. PMID- 26867468 TI - Breast reconstruction by tissue expansion: What is the integrity of the chest wall? AB - BACKGROUND: Both tissue expanders and implants are commonly used during breast reconstructions. These devices are the preferred choice of many plastic surgeons around the world during breast reconstruction due to their technical ease of use, low comorbidity and safety. However, several issues such as the integrity of the chest wall during and after tissue expansion remain unclear. Here we present a longitudinal study that shows deformities of the chest wall caused by the use of tissue expanders. PATIENTS AND METHODS: A prospective longitudinal study of the chest wall in 36 patients who underwent immediate two-stage expander-to-implant reconstruction from 2010 to 2013 was conducted to evaluate the possible causes of chest wall deformity. Computed tomography (CT) scans of the chest walls were taken before the second-stage reconstruction and after 1 year. Chest wall deformities (graded from I, no deformities, to V, costal fracture) were evaluated with CT scans. RESULTS: This study examined 36 breast reconstructions. Chest wall deformities were observed by a CT scan before the second-stage reconstruction. There were eight patients with grade I scores, 14 with grade II, 10 with grade III and four with grade IV. No cases of costal fracture (grade V) were observed. At the 1-year follow-up after the TE/implant change, 22 patients had the same degree of chest wall deformity. Ten patients showed an improvement and four a higher-grade deformity. CONCLUSION: Chest wall deformities commonly occur after tissue expander/implant reconstruction. However, the size of the expander, reconstruction timing and filling volume are not correlated with deformity development. PMID- 26867469 TI - Arterial supply and anastomotic pattern of the infraspinous fossa focusing on the surgical significance. AB - The clinical significance of the muscular branch of the circumflex scapular artery (CSA) has been underestimated during surgery involving the scapular osteocutaneous free flap, while the suprascapular artery (SSA) is vulnerable to damage during internal fixation of a scapular fracture. This study aimed to provide navigational guidelines for the positions of the suprascapular and circumflex scapular arteries at the infraspinous fossa and to identify the anastomotic pattern. Scapulae were carefully dissected following injection of liquid silicone into the suprascapular and circumflex scapular arteries. The artery diameters and the distances between landmarks were measured. Scapulae were classified according to the anastomotic morphology of the arteries. The suprascapular and circumflex scapular arteries had mean diameters of 1.7 and 2.1 mm, respectively. The mean horizontal distance from the root of the spine to the suprascapular artery was 90.3 mm, and the mean distance between the suprascapular and circumflex scapular arteries was 45.5 mm. The circumflex scapular artery was positioned along the lateral border at 68.7% from the inferior angle. Practical navigational guidelines for the positions of the suprascapular and circumflex scapular arteries have been provided, with the anastomotic pattern classified into two types and two subtypes. The results of the present study will help reduce donor-site morbidity and damage to these arteries during surgery in the scapular region. PMID- 26867470 TI - Survey of Portuguese health care professionals attitudes towards non-invasive ventilation in COPD. PMID- 26867471 TI - Effort-reward imbalance at work, over-commitment personality and diet quality in Central and Eastern European populations. AB - The aims of this study were to investigate the associations between work stress defined by the effort-reward imbalance (ERI) model and diet quality and to examine the potential role of over-commitment (OC) personality in ERI-diet relationships. A cross-sectional study was conducted in random population samples of 6340 men and 5792 women (age 45-69 years) from the Czech Republic, Russia and Poland. Dietary data were collected using FFQ. The healthy diet indicator (HDI) was constructed using eight nutrient/food intakes (HDI components) to reflect the adherence to WHO dietary guideline. The extent of imbalance between effort and reward was measured by the effort:reward (ER) ratio; the effort score was the numerator and the reward score was multiplied by a factor adjusting for unequal number of items in the denominator. Logistic regression and linear regression were used to assess the associations between exposures (ER ratio and OC) and outcomes (HDI components and HDI) after adjustment for confounders and mediators. The results showed that high ER ratio and high OC were significantly associated with unhealthy diet quality. For a 1-SD increase in the ER ratio, HDI was reduced by 0.030 and 0.033 sd in men and women, and for a 1-SD increase in OC, HDI was decreased by 0.036 and 0.032 sd in men and women, respectively. The modifying role of OC in ERI-diet relationships was non-significant. To improve diet quality at workplace, a multiple-level approach combining organisational intervention for work stress and individual intervention for vulnerable personality is recommended. PMID- 26867472 TI - High incidence of tuberculosis in patients treated for hepatitis C chronic infection. AB - Brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during alpha-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C alpha-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of alpha-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting alpha interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection. PMID- 26867473 TI - Are opossums a relevant factor associated with asymptomatic Leishmania infection in the outskirts of the largest Brazilian cities? AB - A population survey was conducted to explore the prevalence and factors associated with Leishmania infection in the Fercal region of the Federal District. The Fercal region is a group of neighborhoods in Brasilia in which the first cases of visceral leishmaniasis were described. Leishmania infection was established by a positive leishmanin test. Although other tests were performed in the study (an immunochromatographic assay (Kalazar detect((r))) and a molecular assay), only the leishmanin skin test provided sufficient results for the measurement of the disease prevalence. Data on the epidemiological, clinical and environmental characteristics of individuals were collected along with the diagnostic tests. After sampling and enrollment, seven hundred people from 2 to 14 years of age were included in the study. The prevalence of Leishmania infection was 33.28% (95% CI 29.87-36.84). The factors associated with Leishmania infection according to the multivariate analysis were age of more than seven years and the presence of opossums near the home. Age is a known factor associated with Leishmania infection; however, the presence of wild animals, as described, is an understudied factor. The presence of opossums, which are known reservoirs of Leishmania, in peri-urban areas could be the link between the rural and urban occurrence of visceral leishmaniasis in the outskirts of largest Brazilian cities, as suggested by previous studies. PMID- 26867474 TI - Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection. AB - BACKGROUND: Little is known about factors associated with carbapenem-resistant Klebsiella pneumoniae infections in pediatric patients, who are initally colonized with carbapenem-resistant Klebsiella pneumoniae. MATERIALS AND METHODS: A retrospective case-control study was conducted involving pediatric and neonatal intensive care units throughout a five-year period (January 2010-December 2014). Clinical and microbiological data were extracted from Hospital Infection Control Committee reports and patients' medical records. Risk factors were assessed in carbapenem-resistant Klebsiella pneumoniae colonized patients who developed subsequent systemic infection (cases) and compared to carbapenem-resistant Klebsiella pneumoniae colonized patients who did not develop infection (controls). RESULTS: Throughout the study period, 2.6% of patients admitted to neonatal intensive care units and 3.6% of patients admitted to pediatric intensive care units had become colonized with carbapenem-resistant Klebsiella pneumoniae. After a mean of 10.6+/-1.9 days (median: 7 days, range: 2-38 days) following detection of colonization, 39.0% of the carbapenem-resistant Klebsiella pneumoniae colonized patients in pediatric intensive care units and 18.1% of carbapenem-resistant Klebsiella pneumoniae colonized patients in neonatal intensive care units developed systemic carbapenem-resistant Klebsiella pneumoniae infection. Types of systemic carbapenem-resistant Klebsiella pneumoniae infections included bacteremia (n=15, 62.5%), ventilator-associated pneumonia (n=4, 16.6%), ventriculitis (n=2, 8.3%), intraabdominal infections (n=2, 8.3%), and urinary tract infection (n=1, 4.1%). A logistic regression model including parameters found significant in univariate analysis of carbapenem resistant Klebsiella pneumoniae colonization and carbapenem resistant Klebsiella pneumoniae infection groups revealed underlying metabolic disease (OR: 10.1; 95% CI: 2.7-37.2), previous carbapenem use (OR: 10.1; 95% CI: 2.2-40.1), neutropenia (OR: 13.8; 95% CI: 3.1-61.0) and previous surgical procedure (OR: 7.4; 95% CI: 1.9-28.5) as independent risk factors for carbapenem-resistant Klebsiella pneumoniae infection in patients colonized with carbapenem-resistant Klebsiella pneumoniae. Out of 24 patients with carbapenem resistant Klebsiella pneumoniae infection, 4 (16.6%) died of carbapenem-resistant Klebsiella pneumoniae sepsis. CONCLUSION: Asymptomatic colonization with carbapenem-resistant Klebsiella pneumoniae in intensive care units of pediatric departments should alert health care providers about forthcoming carbapenem-resistant Klebsiella pneumoniae infection. Those carbapenem-resistant Klebsiella pneumoniae colonized patients at risk of developing infection due to carbapenem-resistant Klebsiella pneumoniae may be targeted for interventions to reduce subsequent infection occurence and also for timely initiation of empirical carbapenem-resistant Klebsiella pneumoniae active treatment, when necessary. PMID- 26867475 TI - Biosensing using plasmonic nanohole arrays with small, homogenous and tunable aperture diameters. AB - Plasmonic nanohole arrays are widely used for optical label-free molecular detection. An important factor for many applications is the diameter of the apertures. So far nanohole arrays with controllable diameters below 100 nm have not been demonstrated and it has not been systematically investigated how the diameter influences the optical properties. In this work we fine-tune the diameter in short range ordered nanohole arrays down to 50 nm. The experimental far field spectra show how the wavelength of maximum extinction remains unaffected while the transmission maximum blue shifts with smaller diameters. The near field is visualized by numerical simulations, showing a homogenous enhancement throughout the cylindrical void at the transmission maximum for diameters between 50 and 100 nm. For diameters below 50 nm plasmon excitation is no longer possible experimentally or by simulations. Further, we investigate the refractive index sensing capabilities of the smaller holes. As the diameter was reduced, the sensitivity in terms of resonance shift with bulk liquid refractive index was found to be unaltered. However, for the transmission maximum the sensitivity becomes more strongly localized to the hole interior. By directing molecular binding to the bottom of the holes we demonstrate how smaller holes enhance the sensitivity in terms of signal per molecule. A real-time detection limit well below one protein per nanohole is demonstrated. The smaller plasmonic nanoholes should be suitable for studies of molecules confined in small volumes and as mimics of biological nanopores. PMID- 26867476 TI - Insights into Aminophylline and Neurodevelopmental Outcome in Premature Infants. PMID- 26867477 TI - A prospective, randomised, cross-over trial comparing two standard polyvinyl chloride tracheal tubes. Are all the tubes the same? AB - BACKGROUND: A randomised study was conducted on the number of attempts made during the conventional endotracheal intubation of a mannequin using two polyvinyl (PVC) tracheal tubes, apparently similar but from different manufactures: INTERSURGICAL (IS; Intersurgical S.L., Madrid, Spain) and Mallinckrodt (ML; Mallinkrodt Medical S.A., Madrid, Spain). METHODS: A total of 26 anaesthesiologists, in randomly established order (generated by Epidat 3.1) intubated a mannequin twice using a different tube each time. The tubes were masked by painting them to prevent recognition. The main outcome of the study was to compare the number of attempts needed to complete the manoeuvre for each tube. Data on intubation time and failed intubations were also collected. RESULTS: The number of attempts with the ML tube was significantly lower than with the IS tube. Intubation was completed on the first attempt with the ML tube in 93.3% of cases, while using the IS tube the percentage fell to 30.8% (Fisher exact test, P<.001). The time required to complete the manoeuvre was greater with the IS tube (median 10.8seconds, interquartile range 6-22) than with the ML tube (median 4.4seconds, interquartile range 3.5 to 6.3). CONCLUSIONS: The PVC tube from the ML manufacturer was superior when compared with the IS, the latter was also associated with a larger number of attempts to complete intubation using a conventional Macintosh blade. PMID- 26867478 TI - The role of genomic islands in Escherichia coli K1 interactions with intestinal and kidney epithelial cells. AB - The completion of Escherichia coli K1 genome has identified several genomic islands that are present in meningitis-causing E. coli RS218 but absent in the non-pathogenic E. coli MG1655. In this study, the role of various genomic islands in E. coli K1 interactions with intestinal epithelial cells (Caco-2) and kidney epithelial cells (MA104) was determined. Using association assays, invasion assays, and intracellular survival assays, the findings revealed that the genomic island deletion mutants of RS218 related to P fimbriae, S fimbriae, F17-like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, protein secretion system (T1SS for hemolysin; T2SS; T5SS for antigen 43), Iro system and hmu system), invasins (CNF1, IbeA), toxins (alpha-hemolysin), K1 capsule biosynthesis, metabolism (d-serine catabolism, dihydroxyacetone, glycerol, and glyoxylate metabolism), prophage genes, showed reduced interactions with both cell types. Next, we determined the role of various genomic islands in E. coli K1 resistance to serum. When exposed to the normal human serum, the viability of the genomic island deletion mutants related to adhesins such as S fimbriae, P fimbriae, F17 like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, antigen 43 and T5SS for antigen 43, T2SS, and T1SS for hemolysin, Iro system and hmu system, prophage genes, metabolism (sugar metabolism and d-serine catabolism), K1 capsule biosynthesis, and invasins such as CNF1 was affected, suggesting their role in bacteremia. The characterization of these genomic islands should reveal mechanisms of E. coli K1 pathogenicity that could be of value as therapeutic targets. PMID- 26867479 TI - Management of acute appendicitis in a rural population. AB - BACKGROUND: Our system uses a hub and spoke approach to provide surgical care for our rural population. Patients access care anywhere in the system but are transferred centrally for surgical care. We sought to determine if surgical outcome differed depending on where initial care occurred. We chose acute appendicitis (AA) to investigate our care model. METHODS: We identified patients admitted with the diagnosis of AA. Patients were divided into 2 groups, Bassett Medical Center presentation and satellite center (SAT) presentation. Demographics were compared and, time from system access to surgery, time of surgery, and clinical information associated with care. RESULTS: There were no differences regarding any clinically relevant factor. SAT patients had longer mean surgery times, 60.7 minutes vs 51.5 (P=.008). Time to surgery, LOS, and complications were similar. CONCLUSIONS: It is safe to care for AA patients with a hub and spoke approach without putting SAT patients at a disadvantage. PMID- 26867480 TI - Intraoperative management of renal gunshot injuries: is mandatory exploration of Gerota's fascia necessary? AB - BACKGROUND: Many trauma surgeons and trauma centers use routine exploration of Gerota's fascia (GE) for renal gunshot wounds (RGSW). The purpose of this study was to assess whether RGSW can be selectively explored for patients who undergo exploratory laparotomy. METHODS: Retrospective 10-year review of all patients who underwent exploratory laparotomy for abdominal gunshot wounds and had RGSW selectively explored. RESULTS: Sixty-three patients with RGSW underwent exploratory laparotomy. Twenty-eight (44%) underwent GE vs 35 (56%) who did not. Eight (29%) mortalities occurred with GE and 5 (14%) without GE (P < .05). Of GE patients, 14 (50%) had nephrectomy and 14 (50%) had renorrhaphy. Average hospital length of stay with GE was 16.7 days vs 17.9 without GE. Three (9%) renal associated complications occurred without GE and 1 (4%) with GE. CONCLUSIONS: Most patients who suffer RGSW do not require exploration of GE during abdominal exploration. Complication rates due to nonexploration of RGSW are very low with infrequent need for surgical intervention due to renal-associated complications. High nephrectomy rates may be avoided when GE is averted. PMID- 26867481 TI - Risk and contributing factors of ecosystem shifts over naturally vegetated land under climate change in China. AB - Identifying the areas at risk of ecosystem transformation and the main contributing factors to the risk is essential to assist ecological adaptation to climate change. We assessed the risk of ecosystem shifts in China using the projections of four global gridded vegetation models (GGVMs) and an aggregate metric. The results show that half of naturally vegetated land surface could be under moderate or severe risk at the end of the 21(st) century under the middle and high emission scenarios. The areas with high risk are the Tibetan Plateau region and an area extended northeastward from the Tibetan Plateau to northeast China. With the three major factors considered, the change in carbon stocks is the main contributing factor to the high risk of ecosystem shifts. The change in carbon fluxes is another important contributing factor under the high emission scenario. The change in water fluxes is a less dominant factor except for the Tibetan Plateau region under the high emission scenario. Although there is considerable uncertainty in the risk assessment, the geographic patterns of the risk are generally consistent across different scenarios. The results could help develop regional strategies for ecosystem conservation to cope with climate change. PMID- 26867483 TI - Effects of habitual physical activity on microsurgical performance. AB - We investigated the effect of physical activity on microsurgical performance. Forty novice candidates and 6 expert controls did a series of consecutive end-to end microvascular anastomoses. To assess performance, we did a hand motion analysis and correlated the results with levels of habitual physical activity. Higher levels of activity in the novice candidates correlated with slower completion of anastomosis for medical students on day 1 (p=0.0035) and day 5 (p=0.0003). The same pattern was seen for postgraduate trainees on day 1 (p=0.024) and day 5 (p=0.0063). Higher level of activity also correlated with an increase in path length (total distance travelled and direction of travel) and in total movements on day 1 for medical students (p=0.016 and p=0.0021, respectively), and in total path length on day 1 for postgraduate trainees (p=0.0305). PMID- 26867482 TI - Tripartite assembly of RND multidrug efflux pumps. AB - Tripartite multidrug efflux systems of Gram-negative bacteria are composed of an inner membrane transporter, an outer membrane channel and a periplasmic adaptor protein. They are assumed to form ducts inside the periplasm facilitating drug exit across the outer membrane. Here we present the reconstitution of native Pseudomonas aeruginosa MexAB-OprM and Escherichia coli AcrAB-TolC tripartite Resistance Nodulation and cell Division (RND) efflux systems in a lipid nanodisc system. Single-particle analysis by electron microscopy reveals the inner and outer membrane protein components linked together via the periplasmic adaptor protein. This intrinsic ability of the native components to self-assemble also leads to the formation of a stable interspecies AcrA-MexB-TolC complex suggesting a common mechanism of tripartite assembly. Projection structures of all three complexes emphasize the role of the periplasmic adaptor protein as part of the exit duct with no physical interaction between the inner and outer membrane components. PMID- 26867484 TI - Pain Sensitivity in Patients With Major Depression: Differential Effect of Pain Sensitivity Measures, Somatic Cofactors, and Disease Characteristics. AB - Patients with depression often report pain. Evidence regarding altered pain sensitivity in depressed patients remains, however, inconclusive. In a large cross-sectional study we investigated the association between depression and pain sensitivity with regard to 2 different dimensions of pain sensitivity, as well as the effect of somatic cofactors, symptom severity, and subtype of depression. In 735 patients with a current episode of major depression and 456 never-depressed control participants pain thresholds (pressure pain thresholds, PPTs) were measured at the index finger pad and self-rated suprathreshold pain intensity ratings were obtained using the Pain Sensitivity Questionnaire (PSQ)-minor subscore, an instrument that assesses pain intensity in daily life situations. Additionally, lifestyle factors, medical, and psychiatric conditions were assessed. Unadjusted, patients with depression had lower PPTs and higher PSQ minor scores indicating increased pain sensitivity. After adjusting for potential mediators, such as poor sleep quality and physical inactivity, patients did not differ from control participants regarding PPTs, but still had significantly higher PSQ-minor ratings. Among patients with depression, severity of anxiety symptoms predicted higher PSQ-minor scores. In conclusion, we found a differential effect of depression on the 2 pain sensitivity dimensions: Decreased experimentally obtained pain thresholds were explained by depression-associated somatic factors whereas increased self-rated suprathreshold pain intensity ratings were associated with increased anxiety symptoms. PERSPECTIVE: Because increased pain intensity perception is hypothesized to be a risk factor for the development of chronic pain, our findings may contribute to understanding the high incidence of chronic pain in depressed patients. They also encourage clinicians to consider the role of anxiety in treatment programs for pain in patients with depression. PMID- 26867485 TI - Design, synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors. AB - In the present study, we have designed imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives from earlier reported imidazo[1,2 a]pyridine based Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibitors. We synthesized thirty compounds and they were evaluated for MTB PS inhibition study, in vitro anti-TB activities against replicative and non replicative MTB, in vivo activity using Mycobacterium marinum infected Zebra fish and cytotoxicity against RAW 264.7 cell line. Among them compound 2-methyl-N'-(4 phenoxybenzoyl)benzo[d]imidazo[2,1-b]thiazole-3-carbohydrazide (5bc) emerged as potent compound active against MTB PS with IC50 of 0.53+/-0.13 MUM, MIC of 3.53 MUM, 2.1 log reduction against nutrient starved MTB, with 33% cytotoxicity at 50 MUM. It also showed 1.5 log reduction of M. marinum load in Zebra fish at 10mg/kg. PMID- 26867486 TI - 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions. AB - 4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. PMID- 26867487 TI - Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates. AB - A series of new thiophene-based guanylhydrazones (iminoguanidines) were synthesized in high yields using a straightforward two-step procedure. The antifungal activity of compounds was evaluated against a wide range of medicaly important fungal strains including yeasts, molds, and dermatophytes in comparison to clinically used drug voriconazole. Cytotoxic properties of compounds were also determined using human lung fibroblast cell line and hemolysis assay. All guanylhydrazones showed significant activity against broad spectrum of clinically important species of Candida spp., Aspergillus fumigatus, Fusarium oxysporum, Microsporum canis and Trichophyton mentagrophytes, which was in some cases comparable or better than activity of voriconazole. More importantly, compounds 10, 11, 13, 14, 18 and 21 exhibited excellent activity against voriconazole resistant Candida albicans CA5 with very low minimal inhibitory concentration (MIC) values <2 MUg mL(-1). Derivative 14, bearing bromine on the phenyl ring, was the most effective compound with MICs ranging from 0.25 to 6.25 MUg mL(-1). However, bis-guanylhydrazone 18 showed better selectivity in terms of therapeutic index values. In vivo embryotoxicity on zebrafish (Danio rerio) showed improved toxicity profile of 11, 14 and 18 in comparison to that of voriconazole. Most guanylhydrazones also inhibited C. albicans yeast to hyphal transition, essential for its biofilm formation, while 11 and 18 were able to disperse preformed Candida biofilms. All guanylhydrazones showed the equal potential to interact with genomic DNA of C. albicans in vitro, thus indicating a possible mechanism of their action, as well as possible mechanism of observed cytotoxic effects. Tested compounds did not have significant hemolytic effect and caused low liposome leakage, which excluded the cell membrane as a primary target. On the basis of computational docking experiments using both human and cytochrome P450 from Candida it was concluded that the most active guanylhydrazones had minimal structural prerequisites to interact with the cytochrome P450 14alpha-demethylase (CYP51). Promising guanylhydrazone derivatives also showed satisfactory pharmacokinetic profile based on molecular calculations. PMID- 26867488 TI - Rhesus macaques persistently infected with hepatitis E shed virus into urine. PMID- 26867489 TI - Prioritization of HCV treatment in the direct-acting antiviral era: An economic evaluation. AB - BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at L3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in LUK=?1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a L20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment L60,640/L23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB L59,258 and L19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB L9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -L3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high. PMID- 26867491 TI - Reply to "Rhesus macaques persistently infected with hepatitis E shed virus into urine". PMID- 26867490 TI - IL-6 pathway in the liver: From physiopathology to therapy. AB - Interleukin 6 (IL-6) is a pleiotropic four-helix-bundle cytokine that exerts multiple functions in the body. In the liver, IL-6 is an important inducer of the acute phase response and infection defense. IL-6 is furthermore crucial for hepatocyte homeostasis and is a potent hepatocyte mitogen. It is not only implicated in liver regeneration, but also in metabolic function of the liver. However, persistent activation of the IL-6 signaling pathway is detrimental to the liver and might ultimately result in the development of liver tumors. On target cells IL-6 can bind to the signal transducing subunit gp130 either in complex with the membrane-bound or with the soluble IL-6 receptor to induce intracellular signaling. In this review we describe how these different pathways are involved in the physiology and pathophyiology of the liver. We furthermore discuss how IL-6 pathways can be selectively inhibited and therapeutically exploited for the treatment of liver pathologies. PMID- 26867492 TI - Lights on MAIT cells, a new immune player in liver diseases. PMID- 26867493 TI - The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol induced steatohepatitis. AB - BACKGROUND & AIMS: Alcoholic liver disease (ALD) ranges from fatty liver to inflammation and cirrhosis. miRNA-155 is an important regulator of inflammation. In this study, we describe the in vivo role of miR-155 in ALD. METHODS: Wild-type (WT) (C57/BL6J) or miR-155 knockout (KO) and TLR4 KO mice received Lieber DeCarli diet for 5weeks. Some mice received corn oil or CCl4 for 2 or 9weeks. RESULTS: We found that miR-155 KO mice are protected from alcohol-induced steatosis and inflammation. The reduction in alcohol-induced fat accumulation in miR-155 KO mice was associated with increased peroxisome proliferator-activated receptor response element (PPRE) and peroxisome proliferator-activated receptors (PPAR)alpha (miR-155 target) binding and decreased MCP1 production. Treatment with a miR-155 inhibitor increased PPARgamma expression in naive and alcohol treated RAW macrophages. Alcohol increased lipid metabolism gene expression (FABP4, LXRalpha, ACC1 and LDLR) in WT mice and this was prevented in KO mice. Alcohol diet caused an increase in the number of CD163(+) CD206(+) infiltrating macrophages and neutrophils in WT mice, which was prevented in miR-155 KO mice. Kupffer cells isolated from miR-155 KO mice exhibited predominance of M2 phenotype when exposed to M1 polarized signals and this was due to increased C/EBPbeta. Pro-fibrotic genes were attenuated in miR-155 KO mice after alcohol diet or CCl4 treatment. Compared to WT mice, attenuation in CCl4 induced hydroxyproline and alpha-SMA was observed in KO mice. Finally, we show TLR4 signaling regulates miR-155 as TLR4 KO mice showed no induction of miR-155 after alcohol diet. CONCLUSIONS: Collectively our results demonstrated the role of miR 155 in alcohol-induced steatohepatitis and fibrosis in vivo. PMID- 26867494 TI - Novel pre-mRNA splicing of intronically integrated HBV generates oncogenic chimera in hepatocellular carcinoma. AB - BACKGROUND & AIMS: Hepatitis B virus (HBV) integration is common in HBV associated hepatocellular carcinoma (HCC) and may play an important pathogenic role through the production of chimeric HBV-human transcripts. We aimed to screen the transcriptome for HBV integrations in HCCs. METHODS: Transcriptome sequencing was performed on paired HBV-associated HCCs and corresponding non-tumorous liver tissues to identify viral-human chimeric sites. Validation was further performed in an expanded cohort of human HCCs. RESULTS: Here we report the discovery of a novel pre-mRNA splicing mechanism in generating HBV-human chimeric protein. This mechanism was exemplified by the formation of a recurrent HBV-cyclin A2 (CCNA2) chimeric transcript (A2S), as detected in 12.5% (6 of 48) of HCC patients, but in none of the 22 non-HCC HBV-associated cirrhotic liver samples examined. Upon the integration of HBV into the intron of the CCNA2 gene, the mammalian splicing machinery utilized the foreign splice sites at 282nt. and 458nt. of the HBV genome to generate a pseudo-exon, forming an in-frame chimeric fusion with CCNA2. The A2S chimeric protein gained a non-degradable property and promoted cell cycle progression, demonstrating its potential oncogenic functions. CONCLUSIONS: A pre mRNA splicing mechanism is involved in the formation of HBV-human chimeric proteins. This represents a novel and possibly common mechanism underlying the formation of HBV-human chimeric transcripts from intronically integrated HBV genome with functional impact. LAY SUMMARY: HBV is involved in the mammalian pre mRNA splicing machinery in the generation of potential tumorigenic HBV-human chimeras. This study also provided insight on the impact of intronic HBV integration with the gain of splice sites in the development of HBV-associated HCC. PMID- 26867496 TI - Limits of Coherency and Strain Transfer in Flexible 2D van der Waals Heterostructures: Formation of Strain Solitons and Interlayer Debonding. AB - In flexible 2D-devices, strain transfer between different van-der Waals stacked layers is expected to play an important role in determining their optoelectronic performances and mechanical stability. Using a 2D non-linear shear-lag model, we demonstrate that only 1-2% strain can be transferred between adjacent layers of different 2d-materials, depending on the strength of the interlayer vdW interaction and the elastic modulus of the individual layers. Beyond this critical strain, layers begin to slip with respect to each other. We further show that due to the symmetry of the periodic interlayer shear potential, stacked structures form strain solitons with alternating AB/BA or AB/AB stacking which are separated by incommensurate domain walls. The extent and the separation distance of these commensurate domains are found to be determined by the degree of the applied strain, and their magnitudes are calculated for several 2D heterostructures and bilayers including MoS2/WS2, MoSe2/WSe2, Graphene/Graphene and MoS2/MoS2 using a multiscale method. As bilayer structures have been shown to exhibit stacking-dependent electronic bandgap and quantum transport properties, the predictions of our study will not only be crucial in determining the mechanical stability of flexible 2D devices but will also help to better understand optoelectronic response of flexible devices. PMID- 26867495 TI - Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites. AB - The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD(+)) via the mycobacterial catalase-peroxidase enzyme, KatG, has been described as the major component of the mode of action of isoniazid (INH). However, there are numerous human peroxidases that may catalyze this reaction. The role of neutrophil myeloperoxidase (MPO) in INH-NAD(+) adduct formation has never been explored; this is important, as neutrophils are recruited at the site of tuberculosis infection (granuloma) through infected macrophages' cell death signals. In our studies, we showed that neutrophil MPO is capable of INH metabolism using electron paramagnetic resonance (EPR) spin-trapping and UV-Vis spectroscopy. MPO or activated human neutrophils (by phorbol myristate acetate) catalyzed the oxidation of INH and formed several free radical intermediates; the inclusion of superoxide dismutase revealed a carbon-centered radical which is considered to be the reactive metabolite that binds with NAD(+). Other human metabolites, including N-acetyl-INH, N-acetylhydrazine, and hydrazine did not show formation of carbon-centered radicals, and either produced no detectable free radicals, N-centered free radicals, or superoxide, respectively. A comparison of these free radical products indicated that only the carbon-centered radical from INH is reducing in nature, based on UV-Vis measurement of nitroblue tetrazolium reduction. Furthermore, only INH oxidation by MPO led to a new product (lambdamax=326nm) in the presence of NAD(+). This adduct was confirmed to be isonicotinyl-NAD(+) using LC-MS analysis where the intact adduct was detected (m/z=769). The findings of this study suggest that neutrophil MPO may also play a role in INH pharmacological activity. PMID- 26867497 TI - Decisions in Motion: Decision Dynamics during Intertemporal Choice reflect Subjective Evaluation of Delayed Rewards. AB - People tend to discount rewards or losses that occur in the future. Such delay discounting has been linked to many behavioral and health problems, since people choose smaller short-term gains over greater long-term gains. We investigated whether the effect of delays on the subjective value of rewards is expressed in how people move when they make choices. Over 600 patrons of the RISK LAB exhibition hosted by the Science Gallery Dublin(TM) played a short computer game in which they used a computer mouse to choose between amounts of money at various delays. Typical discounting effects were observed and decision dynamics indicated that choosing smaller short-term rewards became easier (i.e., shorter response times, tighter trajectories, less vacillation) as the delays until later rewards increased. Based on a sequence of choices, subjective values of delayed outcomes were estimated and decision dynamics during initial choices predicted these values. Decision dynamics are affected by subjective values of available options and thus provide a means to estimate such values. PMID- 26867498 TI - Application of cosmetic nail varnish does not affect the antifungal efficacy of amorolfine 5% nail lacquer in the treatment of distal subungual toenail onychomycosis: results of a randomised active-controlled study and in vitro assays. AB - As onychomycosis is unsightly, this study clinically evaluated whether the antifungal efficacy of amorolfine 5% nail lacquer (NL) was affected by a masking, natural-coloured, cosmetic nail varnish applied 24 h later; in vitro investigations were also performed. Subjects with mild-to-moderate distal subungual toenail onychomycosis were randomised to receive amorolfine 5% NL once weekly with or without cosmetic nail varnish applied 24 h later. After 12-week treatment, antifungal activity of affected toenail clippings was assessed by measurement of zones of inhibition (ZOIs) on Trichophyton mentagrophytes seeded agar plates. Mean diameters were 53.5 mm for the amorolfine 5% NL-alone group (n = 23) and 53.6 mm for amorolfine 5% NL plus cosmetic nail varnish group (n = 25). Also, mycological cultures of subungual debris at week 12 were negative for all subjects in both groups. Most subjects (88%) reported that cosmetic nail varnish masked their infected toenails. Additionally, cadaver human nails coated in vitro with or without cosmetic nail varnish 10 min or 24 h post amorolfine NL application all gave ZOIs on Trichophyton rubrum agar plates representing potent antifungal activity. In conclusion, cosmetic nail varnish applied post amorolfine had no effect on the subungual antifungal activity of amorolfine 5% NL or its penetration through toenails. PMID- 26867499 TI - Activation and Connectivity within the Default Mode Network Contribute Independently to Future-Oriented Thought. AB - Future-oriented thought, a projection of the self into the future to pre experience an event, has been linked to default mode network (DMN). Previous studies showed that the DMN was generally divided into two subsystems: anterior part (aDMN) and posterior part (pDMN). The former is mostly related to self referential mental thought and latter engages in episodic memory retrieval and scene construction. However, functional contribution of these two subsystems and functional connectivity between them during future-oriented thought has rarely been reported. Here, we investigated these issues by using an experimental paradigm that allowed prospective, episodic decisions concerning one's future (Future Self) to be compared with self-referential decisions about one's immediate present state (Present Self). Additionally, two parallel control conditions that relied on non-personal semantic knowledge (Future Non-Self Control and Present Non-Self Control) were conducted. Our results revealed that the aDMN was preferentially activated when participants reflected on their present states, whereas the pDMN exhibited preferentially activation when participants reflected on their personal future. Intriguingly, significantly decreased aDMN-pDMN connectivity was observed when thinking about their future relative to other conditions. These results support the notion that activation within these subsystems and connectivity between them contribute differently to future-oriented thought. PMID- 26867501 TI - Corrigendum. PMID- 26867502 TI - Nematode-bacteria mutualism: Selection within the mutualism supersedes selection outside of the mutualism. AB - The coevolution of interacting species can lead to codependent mutualists. Little is known about the effect of selection on partners within verses apart from the association. Here, we determined the effect of selection on bacteria (Xenorhabdus nematophila) both within and apart from its mutualistic partner (a nematode, Steinernema carpocapsae). In nature, the two species cooperatively infect and kill arthropods. We passaged the bacteria either together with (M+), or isolated from (M-), nematodes under two different selection regimes: random selection (S-) and selection for increased virulence against arthropod hosts (S+). We found that the isolated bacteria evolved greater virulence under selection for greater virulence (M-S+) than under random selection (M-S-). In addition, the response to selection in the isolated bacteria (M-S+) caused a breakdown of the mutualism following reintroduction to the nematode. Finally, selection for greater virulence did not alter the evolutionary trajectories of bacteria passaged within the mutualism (M+S+ = M+S-), indicating that selection for the maintenance of the mutualism was stronger than selection for increased virulence. The results show that selection on isolated mutualists can rapidly breakdown beneficial interactions between species, but that selection within a mutualism can supersede external selection, potentially generating codependence over time. PMID- 26867500 TI - Efficacy of naringenin against permethrin-induced testicular toxicity in rats. AB - Permethrin (PM), a synthetic pyrethroid insecticide, has broad toxicity spectra. We aimed to investigate the effects of PM on the testes of adult albino rats, examine the recovery response and evaluate the efficacy of naringenin (NG) supplementation. Adult male albino rats were randomly assigned to five groups of six each: control, NG (50 mg/kg), PM (70 mg/kg), recovery (after subsequent withdrawal of PM) and NG-PM group. All treatments were given by oral gavage for 6 weeks and another 3 weeks for the recovery group. At the time of sacrifice, each testis was weighed. Biochemical analysis of epididymal sperm count and serum testosterone level was performed. Testes were processed for histological, ultrastructural and c-Kit immunohistochemical study. PM toxicity was evidenced by a highly significant decrease in testicular weight, epididymal sperm count and serum testosterone level compared to control. Furthermore, testicular structure abnormalities and reduced c-Kit immunoreactions were observed. Stoppage of PM in the recovery group partially reversed PM-induced changes. There was a mild decrease in testicular weight and biochemical parameters compared to control. The structure of seminiferous tubules was partially retained. The NG-PM group showed an overall improvement in testicular weight and biochemical alterations which were confirmed by light and electron microscopic examination. In conclusion, PM induced testicular toxicity, which was ameliorated by NG co-administration. However, stoppage of PM exposure was associated with partial recovery. PMID- 26867503 TI - (I) Pharmacological profiling of a novel modulator of the alpha7 nicotinic receptor: Blockade of a toxic acetylcholinesterase-derived peptide increased in Alzheimer brains. AB - The primary cause of Alzheimer's disease is unlikely to be the much studied markers amyloid beta or tau. Their widespread distribution throughout the brain does not account for the specific identity and deep subcortical location of the primarily vulnerable neurons. Moreover an unusual and intriguing feature of these neurons is that, despite their diverse transmitters, they all contain acetylcholinesterase. Here we show for the first time that (1) a peptide derived from acetylcholinesterase, with independent trophic functions that turn toxic in maturity, is significantly raised in the Alzheimer midbrain and cerebrospinal fluid; (2) a synthetic version of this peptide enhances calcium influx and eventual production of amyloid beta and tau phosphorylation via an allosteric site on the alpha7 nicotinic receptor; (3) a synthetic cyclic version of this peptide is neuroprotective against the toxicity not only of its linear counterpart but also of amyloid beta, thereby opening up the prospect of a novel therapeutic approach. PMID- 26867504 TI - Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands. AB - BACKGROUND AND PURPOSE: Nociceptin/orphanin FQ (N/OFQ) receptor (NOP) agonists produce anxiolytic-like effects in rodents while antagonists promote antidepressant-like effects. The aim of this study was to investigate the effect on anxiety and depression of NOP receptor partial agonists such as the peptides [F/G]N/OFQ(1-13)NH2 and UFP-113 and the non-peptide AT-090. EXPERIMENTAL APPROACH: In vitro AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 were tested for their ability to promote NOP/G-protein and NOP/beta-arrestin 2 interaction, using a bioluminescence resonance energy transfer assay. In vivo, they were tested in mice in the elevated plus maze (EPM) and in the forced swim (FST) tests. NOP partial agonists effects were systematically compared to those of full agonists (N/OFQ and Ro 65-6570) and antagonists (UFP-101 and SB-612111). KEY RESULTS: In vitro, AT-090, UFP-113, and [F/G]N/OFQ(1-13)NH2 promoted NOP/G protein interaction, with maximal effects lower than those evoked by N/OFQ and Ro 65 6570. AT-090 behaved as a NOP partial agonist also in inducing beta-arrestin 2 recruitment, while UFP-113 and [F/G]N/OFQ(1-13)NH2 were inactive in this assay. In vivo, AT-090 induced anxiolytic-like effects in the EPM but was inactive in the FST. Opposite results were obtained with UFP-113 and [F/G]N/OFQ(1-13)NH2. CONCLUSIONS AND IMPLICATIONS: NOP ligands producing similar effects on NOP/G protein interaction (partial agonism) but showing different effects on beta arrestin 2 recruitment (partial agonism vs antagonism) elicited different actions on anxiety and mood. These results suggest that the action of a NOP ligand on emotional states is better predicted based on its beta-arrestin 2 rather than G protein efficacy. PMID- 26867506 TI - Failure and rescue of preconditioning-induced neuroprotection in severe stroke like insults. AB - Preconditioning is a well established neuroprotective modality. However, the mechanism and relative efficacy of neuroprotection between diverse preconditioners is poorly defined. Cultured neurons were preconditioned by 4 aminopyridine and bicuculline (4-AP/bic), rendering neurons tolerant to normally lethal (sufficient to kill most neurons) oxygen-glucose deprivation (OGD) or a chemical OGD-mimic, ouabain/TBOA, by suppression of extracellular glutamate (glutamateex) elevations. However, subjecting preconditioned neurons to longer duration supra-lethal insults caused neurotoxic glutamateex elevations, thereby identifying a 'ceiling' to neuroprotection. Neuroprotective 'rescue' of neurons could be obtained by administration of an NMDA receptor antagonist, MK-801, just before glutamateex rose during these supra-lethal insults. Next, we evaluated if these concepts of glutamateex suppression during lethal OGD, and a neuroprotective ceiling requiring MK-801 rescue under supra-lethal OGD, extended to the preconditioning field. In screening a panel of 42 diverse putative preconditioners, neuroprotection against normally lethal OGD was observed in 12 cases, which correlated with glutamateex suppression, both of which could be reversed, either by the inclusion of a glutamate uptake inhibitor (TBOA, to increase glutamateex levels) during OGD or by exposure to supra-lethal OGD. Administrating MK-801 during the latter stages of supra-lethal OGD again rescued neurons, although to varying degrees dependent on the preconditioning agent. Thus, 'stress-testing' against the harshest ischemic-like insults yet tested identifies the most efficacious preconditioners, which dictates how early MK-801 needs to be administered during the insult in order to maintain neuroprotection. Preconditioning delays a neurotoxic rise in glutamateex levels, thereby 'buying time' for acute anti-excitotoxic pharmacologic rescue. PMID- 26867507 TI - Prediction of orthostatic hypotension in multiple system atrophy and Parkinson disease. AB - Orthostatic hypotension (OH) is common in multiple system atrophy (MSA) and Parkinson disease (PD), generally assessed through a lying-to-standing orthostatic test. However, standing blood pressure may not be available due to orthostatic intolerance or immobilization for such patients. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were successively measured in supine, sitting, and standing positions in patients with MSA and PD. Receiver operating characteristic analysis was used to evaluate diagnostic performance of the drops of sitting SBP or DBP. OH and severe OH were respectively regarded as "gold standard". The drops of SBP in standing position were associated with increased disease severity for MSA and correlated with age for PD. In MSA group, drops in sitting SBP >= 14 mmHg or DBP >= 6 mmHg had highest validity for prediction of OH, and drops in sitting SBP >= 18 mmHg or DBP >= 8 mmHg for severe OH. In PD group, drops in sitting SBP >= 10 mmHg or DBP >= 6 mmHg had highest validity for prediction of OH. The lying-to-sitting orthostatic test is an alternative method for detection of OH in MSA and PD, especially when standing BP could not be validly measured due to various reasons. PMID- 26867505 TI - Activation of alpha7 nicotinic acetylcholine receptors protects potentiated synapses from depotentiation during theta pattern stimulation in the hippocampal CA1 region of rats. AB - Long-term potentiation (LTP) shows memory-like consolidation and thus becomes increasingly resistant to disruption by low-frequency stimulation (LFS). However, it is known that nicotine application during LFS uniquely depotentiates consolidated LTP. Here, we investigated how nicotine contributes to the disruption of stabilized LTP in the hippocampal CA1 region. We found that nicotine-induced depotentiation is not due to masking LTP by inducing long-term depression and requires the activation of GluN2A-containing NMDARs. We further examined whether nicotine-induced depotentiation involves the reversal of LTP mechanisms. LTP causes phosphorylation of Ser-831 on GluA1 subunits of AMPARs that increases the single-channel conductance of AMPARs. This phosphorylation remained unchanged after depotentiation. LTP involves the insertion of new AMPARs into the synapse and the internalization of AMPARs is associated with dephosphorylation of Ser-845 on GluA1 and caspase-3 activity. Nicotine-induced depotentiation occurred without dephosphorylation of the Ser-845 and in the presence of a caspase-3 inhibitor. LTP is also accompanied by increased filamentous actin (F-actin), which controls spine size. Nicotine-induced depotentiation was prevented by jasplakinolide, which stabilizes F-actin, suggesting that nicotine depotentiates consolidated LTP by destabilizing F-actin. alpha7 nicotinic acetylcholine receptor (nAChR) antagonists mimicked the effect of nicotine and selective removal of hippocampal cholinergic input caused depotentiation in the absence of nicotine, suggesting that nicotine depotentiates consolidated LTP by inducing alpha7 nAChR desensitization. Our results demonstrate a new role for nicotinic cholinergic systems in protecting potentiated synapses from depotentiation by preventing GluN2A-NMDAR-mediated signaling for actin destabilization. PMID- 26867508 TI - Deep procedural sedation by a sedationist team for outpatient pediatric renal biopsies. AB - To date, no study has analyzed the use of deep PS for pediatric renal biopsies by a dedicated sedation team in an outpatient setting. Retrospective analysis of renal biopsies performed at CHOA from 2009 to 2013. Patient demographics, procedure success, and sedation-related events were analyzed. Logistic regression techniques were applied to identify characteristics associated with procedure safety and success. A total of 174 biopsies from 136 patients, aged 2-21 yr, were reviewed. Of the 174 biopsies, 63 of 174 (36%) were from native, and 111 of 174 (64%) were from transplanted kidneys, respectively. No deaths, allograft losses, or unanticipated hospital admissions occurred. The most commonly utilized interventions during sedation were blow-by oxygen (29.9%) and CPAP (12.1%). Children receiving the combination of F + P had significantly higher biopsy success rates vs. other drug combinations (96.1% vs. 79%; p = 0.014). There was no difference in complication rates regardless of drug combination or biopsy type (transplanted vs. native). The combination of F + P yields a high procedural success rate for outpatient native and transplanted kidney biopsies. We identified a number of sedation-related events that can be easily managed by a well-trained sedationist team. PMID- 26867509 TI - Temple syndrome: A patient with maternal hetero-UPD14, mixed iso- and hetero disomy detected by SNP microarray typing of patient-father duos. AB - Temple syndrome (TS, MIM 616222) is an imprinting disorder involving genes within the imprinted region of chromosome 14q32. TS is a genetically complex disorder, which is associated with maternal uniparental disomy of chromosome 14 (UPD14), paternal deletions on chromosome 14, or loss of methylation at the intergenic differentially methylated region (IG-DMR). Here, we describe the case of a patient with maternal hetero-UPD14, mixed iso-/hetero-disomy mechanism identified by a single nucleotide polymorphism (SNP) array analysis of patient-father duos study. The phenotype of our case is similarities to Prader-Willi syndrome (PWS) during infancy and to Russell-Silver syndrome (RSS) during childhood. This SNP array appears to be an effective initial screening tool for patients with nonspecific clinical features suggestive of chromosomal disorders. PMID- 26867510 TI - Electroclinical phenotype in Rubinstein-Taybi syndrome. AB - OBJECTIVE: Rubinstein-Taybi syndrome (RSTS) is a rare congenital disorder (1:125.000) characterized by growth retardation, psychomotor developmental delay, microcephaly and dysmorphic features. In 25% of patients seizures have been described, and in about 66% a wide range of EEG abnormalities, but studies on neurological features are scant and dated. The aim of this study is to describe the electroclinical phenotype of twenty-three patients with RSTS, and to try to correlate electroclinical features with neuroradiological, cognitive and genetic features. PATIENTS AND METHODS: Electroclinical features of twenty-three patients with RSTS (age between18months and 20years) were analyzed. Sleep and awake EEG was performed in twenty-one patients, and brain MRI in nineteen patients. All subjects received cognitive evaluation. RESULTS: EEG abnormalities were observed in 76% (16/21) of patients. A peculiar pattern prevalent in sleep, characterized by slow monomorphic activity on posterior regions was also observed in 33% (7/21) of patients. Almost no patient presented seizures. Eighty-four percentage of patients had brain MRI abnormalities, involving corpus callosum and/or posterior periventricular white matter. Average General Quotient (GQ) was 52, while average IQ was 55, corresponding to mild Intellectual Disability. The homogeneous electroclinical pattern was observed mainly in patients with more severe neuroradiologic findings and moderate Intellectual Disability/Developmental Disability (ID/DD). No genotype-phenotype correlations were found. CONCLUSION: The specific electroclinical and neuroradiological features described may be part of a characteristic RSTS phenotype. Wider and longitudinal studies are needed to verify its significance and impact on diagnosis, prognosis and clinical management of RSTS patients. PMID- 26867512 TI - Computed Tomographic Screening for Lung Cancer Trends at Leading Academic Medical Centers From 2013 to 2015. PMID- 26867511 TI - Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation. AB - We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patient's father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21. PMID- 26867513 TI - Spectroscopic, structural and computational analysis of [Re(CO)3(dippM)Br](n+) (dippM = 1,1'-bis(diiso-propylphosphino)metallocene, M = Fe, n = 0 or 1; M = Co, n = 1). AB - While the redox active backbone of bis(phosphino)ferrocene ligands is often cited as an important feature of these ligands in catalytic studies, the structural parameters of oxidized bis(phosphino)ferrocene ligands have not been thoroughly studied. The reaction of [Re(CO)3(dippf)Br] (dippf = 1,1'-bis(diiso propylphosphino)ferrocene) and [NO][BF4] in methylene chloride yields the oxidized compound, [Re(CO)3(dippf)Br][BF4]. The oxidized species, [Re(CO)3(dippf)Br][BF4], and the neutral species, [Re(CO)3(dippf)Br], are compared using X-ray crystallography, cyclic voltammetry, visible spectroscopy, IR spectroscopy and zero-field (57)Fe Mossbauer spectroscopy. In addition, the magnetic moment of the paramagnetic [Re(CO)3(dippf)Br][BF4] was measured in the solid state using SQUID magnetometry and in solution by the Evans method. The electron transfer reaction of [Re(CO)3(dippf)Br][BF4] with acetylferrocene was also examined. For additional comparison, the cationic compound, [Re(CO)3(dippc)Br][PF6] (dippc = 1,1'-bis(diiso-propylphosphino)cobaltocenium), was prepared and characterized by cyclic voltammetry, X-ray crystallography, and NMR, IR and visible spectroscopies. Finally, DFT was employed to examine the oxidized dippf ligand and the oxidized rhenium complex, [Re(CO)3(dippf)Br](+). PMID- 26867514 TI - Preface: Issue 30.3. PMID- 26867518 TI - Instructions for Contributors. PMID- 26867515 TI - Magnetic field induced motion behavior of gas bubbles in liquid. AB - The oxygen evolution reaction generally exists in electrochemical reactions. It is a ubiquitous problem about how to control the motion of oxygen bubbles released by the reaction. Here we show that oxygen bubbles during oxygen evolution reaction exhibit a variety of movement patterns in the magnetic field, including directional migration and rotational motion of oxygen bubbles when the magnet in parallel with the electrode, and exclusion movement of oxygen bubbles when the magnet perpendicular to the electrode. The results demonstrate that the direction of oxygen bubbles movement is dependent upon the magnet pole near the electrode, and the kinetics of oxygen bubbles is mainly proportional to intensity of the electromagnetic field. The magnetic-field induced rotational motion of oxygen bubbles in a square electrolyzer can increase liquid hydrodynamics, thus solve the problems of oxygen bubbles coalescence, and uneven distribution of electrolyte composition and temperature. These types of oxygen bubbles movement will not only improve energy saving and metal deposition for energy storage and metal refinery, but also propel object motion in application to medical and martial fields. PMID- 26867519 TI - Seasonality of water quality and diarrheal disease counts in urban and rural settings in south India. AB - The study examined relationships among meteorological parameters, water quality and diarrheal disease counts in two urban and three rural sites in Tamil Nadu, India. Disease surveillance was conducted between August 2010 and March 2012; concurrently water samples from street-level taps in piped distribution systems and from household storage containers were tested for pH, nitrate, total dissolved solids, and total and fecal coliforms. Methodological advances in data collection (concurrent prospective disease surveillance and environmental monitoring) and analysis (preserving temporality within the data through time series analysis) were used to quantify independent effects of meteorological conditions and water quality on diarrheal risk. The utility of a local calendar in communicating seasonality is also presented. Piped distribution systems in the study area showed high seasonal fluctuations in water quality. Higher ambient temperature decreased and higher rainfall increased diarrheal risk with temperature being the predominant factor in urban and rainfall in rural sites. Associations with microbial contamination were inconsistent; however, disease risk in the urban sites increased with higher median household total coliform concentrations. Understanding seasonal patterns in health outcomes and their temporal links to environmental exposures may lead to improvements in prospective environmental and disease surveillance tailored to addressing public health problems. PMID- 26867520 TI - Physicochemical and sensory characteristics of yoghurts made from goat and cow milk. AB - Substituting goats' milk for cows' milk could improve the quality of dairy products, because it adds new sensorial characteristics. The aim of this study was to develop a type of yoghurt using goats' milk (25, 50, 75 and 100%) in place of cows' milk and to compare their characteristics. Physicochemical, microbiological and sensory characteristics were evaluated using a nine-point hedonic scale and purchase intention test. The data obtained in the physicochemical analysis were submitted to regression analysis and the sensory results were evaluated through analysis of variance. Among the physicochemical characteristics of the yoghurts, variation (P < 0.05) of ash, acidity and lactose was observed. Tasters in the sensory analysis indicated that yoghurts up to 50% of goats' milk received favorable averages; with lower scores for higher goats' milk concentrations (75% and 100%). No difference was reported in acidity. Replacing cows' milk with goats' milk in yoghurt preparation promotes variations in the physicochemical characteristics for ash, acidity and lactose. However, it does not cause alterations in the sensory attributes (50% goat milk) and therefore could be considered as an alternative for the production of dairy products. (c) 2016 Japanese Society of Animal Science. PMID- 26867521 TI - Quantitative proteomics suggests metabolic reprogramming during ETHE1 deficiency. AB - Deficiency of mitochondrial sulfur dioxygenase (ETHE1) causes the severe metabolic disorder ethylmalonic encephalopathy, which is characterized by early onset encephalopathy and defective cytochrome C oxidase because of hydrogen sulfide accumulation. Although the severe systemic consequences of the disorder are becoming clear, the molecular effects are not well defined. Therefore, for further elucidating the effects of ETHE1-deficiency, we performed a large scale quantitative proteomics study on liver tissue from ETHE1-deficient mice. Our results demonstrated a clear link between ETHE1-deficiency and redox active proteins, as reflected by downregulation of several proteins related to oxidation reduction, such as different dehydrogenases and cytochrome P450 (CYP450) members. Furthermore, the protein data indicated impact of the ETHE1-deficiency on metabolic reprogramming through upregulation of glycolytic enzymes and by altering several heterogeneous ribonucleoproteins, indicating novel link between ETHE1 and gene expression regulation. We also found increase in total protein acetylation level, pointing out the link between ETHE1 and acetylation, which is likely controlled by both redox state and cellular metabolites. These findings are relevant for understanding the complexity of the disease and may shed light on important functions influenced by ETHE1 deficiency and by the concomitant increase in the gaseous mediator hydrogen sulfide. All MS data have been deposited in the ProteomeXchange with the dataset identifiers PXD002741 (http://proteomecentral.proteomexchange.org/dataset/PXD002741) and PXD002742 (http://proteomecentral.proteomexchange.org/dataset/PXD002741). PMID- 26867523 TI - Epidermal growth factor receptor inhibitor AG1478 inhibits mucus hypersecretion in airway epithelium. AB - BACKGROUND: Mucus hypersecretion and neutrophil infiltration are important characteristics of airway inflammation. Epidermal growth factor receptor (EGFR) transactivation induces mucus and inflammatory cytokine secretion from airway epithelial cells. To elucidate the roles of EGFR in airway inflammation, the in vitro effects on mucin production and interleukin (IL) 8 secretion from cultured airway epithelial cells and the in vivo effects on mucus hypersecretion and neutrophil infiltration in rat nasal mucosa of the EGFR tyrosine kinase inhibitor AG1478 were examined. METHODS: The in vitro effects of AG1478 treatment of cultured NCI-H292 cells on lipopolysaccharide (LPS) induced or tumor necrosis factor (TNF) alpha induced MUC5AC mucin and IL-8 secretion were evaluated. Hypertrophic and metaplastic changes of goblet cells, mucus production and neutrophil infiltration in rat nasal epithelium were induced by intranasal instillation of LPS in vivo, and the inhibitory effects of AG1478 by intraperitoneal injection or intranasal instillation were examined. RESULTS: AG1478 (1-1000 nM) significantly inhibited both LPS-induced and TNF-alpha-induced secretion of MUC5AC and IL-8 from cultured NCI-H292 cells in a dose-dependent manner. The expression of MUC5AC and IL-8 messenger RNAs was also significantly inhibited. Intranasal instillation of AG1478 one hour after intranasal LPS instillation significantly inhibited LPS-induced goblet cell metaplasia, mucus production, and neutrophil infiltration in rat nasal epithelium, as did intraperitoneal injection of AG1478 one hour before LPS instillation. CONCLUSIONS: These results indicated that EGFR transactivation plays an important role in mucin and IL-8 secretion from airway epithelial cells. Intranasal instillation of an EGFR tyrosine kinase inhibitor may be a new therapeutic approach for the treatment of upper airway inflammation. PMID- 26867524 TI - Editorial: The microbiome of the sinuses and its relevance in health and disease. PMID- 26867522 TI - The antimicrobial action of resveratrol against Listeria monocytogenes in food based models and its antibiofilm properties. AB - BACKGROUND: Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural phytoalexin synthesized by plants in response to stress. This compound has several beneficial documented properties, namely anti-inflammatory, antioxidant, neuroprotective and antimicrobial activities. In this study the antimicrobial activity of resveratrol against Listeria monocytogenes and Listeria innocua was investigated. RESULTS: Resveratrol had a minimum inhibitory concentration of 200 ug mL(-1) for the tested strains, with time-kill curves demonstrating bacteriostatic activity. Inhibition of biofilm formation was also assessed, with resveratrol strongly inhibiting biofilm formation by both species even at subinhibitory concentrations. Overall, resveratrol showed antimicrobial properties on planktonic cells and on biofilm formation ability. Considering the potential use of resveratrol as a food preservative, the antimicrobial efficacy of resveratrol in food was studied in milk, lettuce leaf model and chicken juice. Resveratrol retained greater efficacy in both lettuce leaf model and chicken juice, but milk had a negative impact on its antilisterial activity, indicating a possible reduction of resveratrol availability in milk. CONCLUSION: This study reinforces resveratrol as an antimicrobial agent, pointing out its antibiofilm activity and its potential use as preservative in some food matrices. (c) 2016 Society of Chemical Industry. PMID- 26867526 TI - The relationship between serum vitamin D and chronic rhinosinusitis: A systematic review. AB - BACKGROUND: An exciting development in upper respiratory tract disease is the pathophysiology of vitamin D (VD3). There now is substantial literature to indicate that VD3 acts as an immunomodulator of adaptive and innate immunity locally within the respiratory epithelium. Chronic rhinosinusitis (CRS) places a relatively large socioeconomic burden on developed nations, yet remains a difficult disease to treat. VD3, therefore, has become an area of clinical interest because it may provide an adjunctive drug therapy option in CRS, thereby potentially improving the quality of life of these patients. OBJECTIVE: A systematic review of the relationship among serum VD3 levels, CRS phenotype, and disease severity by using outcome assessments. METHODS: A systematic search was performed by using the PubMed, MEDLINE, and EMBASE databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies that measured serum VD3 levels and correlated the measurements to any subtype of CRS (with or without nasal polyps) were included for qualitative analysis. RESULTS: Seven articles were included (four prospective and three retrospective studies), with a total of 539 patients. There were significantly lower VD3 levels in the polypoid phenotypes of CRS compared with controls. Low VD3 levels were often associated with an increased degree of inflammation. CONCLUSION: The available evidence indicated that there is a significant relationship between low VD3 levels and polypoid CRS phenotypes. The association between VD3 levels and disease severity and VD3 potential for drug therapy remains unclear, which warrants further research in the area. PMID- 26867525 TI - Microbiome of the paranasal sinuses: Update and literature review. AB - BACKGROUND: Our understanding of the resident microbiome of the paranasal sinuses has changed considerably in recent years. Once presumed to be sterile, healthy sinus cavities are now known to harbor a diverse assemblage of microorganisms, and, it is hypothesized that alterations in the kinds and quantities of these microbes may play a role in the pathogenesis of chronic rhinosinusitis (CRS). OBJECTIVES: To review the current literature regarding the sinus microbiome and collate research findings from relevant studies published to date. METHODS: A systematic literature review was performed on all molecular studies that investigated the microbial communities of the paranasal sinuses. Methods of detection, microbiome composition, and comparative profiling between patients with and without CRS were explored. RESULTS: A complex consortium of microorganisms has been demonstrated in the sinuses of both patients with and without CRS. However, the latter generally have been characterized by reduced biodiversity compared with controls, with selective enrichment of particular microbes (e.g., Staphylococcus aureus). Such disruptions in the resident microbiome may contribute to disease pathogenesis by enhancing the virulence of potential pathogens and adversely modulating immune responses. CONCLUSION: The advent of culture-independent molecular approaches has led to a greater appreciation of the intricate microbial ecology of the paranasal sinuses. Microbiota composition, distribution, and abundance impact mucosal health and influence pathogen growth and function. A deeper understanding of the host microbiome relationship and its constituents may encourage development of new treatment paradigms for CRS, which target restoration of microbiome homeostasis and cultivation of optimal microbial communities. PMID- 26867528 TI - The bacterial microbiome in chronic rhinosinusitis: Richness, diversity, postoperative changes, and patient outcomes. AB - BACKGROUND: The bacterial microbiome in chronic rhinosinusitis (CRS) remains poorly understood. Microorganisms are believed to be important contributors to the inflammatory response seen in these patients. OBJECTIVE: To examine the bacterial CRS microbiome by using a pyrosequencing technique and determine the diversity, richness, prevalence, and abundance of bacterial species in these patients. Furthermore, the postoperative changes that occur in the microbiome and correlations with patient outcomes are assessed. METHODS: Swabs were collected from 23 patients with CRS and 11 controls during surgery. Further postoperative swabs were collected in the CRS group. Bacterial DNA was extracted from the swabs and then sequenced by using 16S ribosomal DNA bacterial tag-encoded FLX amplicon pyrosequencing. RESULTS: A total of 456 unique bacterial species were detected. No difference was seen for richness or diversity between the study groups (p > 0.05). Diversity declined after surgery in the CRS group (p = 0.01). Propionibacterium acnes and Staphylococcus epidermidis were the most prevalent species. Several significant differences were determined for prevalence and mean relative abundance (MRA) between the study groups. In particular, Acinetobacter johnsonii was more prevalent and had a higher MRA in the controls. Furthermore, the MRA of this species increased after surgery and was associated with improved quality of life. CONCLUSION: This study characterized the sinonasal microbiome in a group of controls and patients with CRS. Important differences in diversity, prevalence, abundance, and temporal changes were described. Of great interest is the potential association between A. johnsonii and health. These findings provide new insights into the interplay between the microbiome and health in the paranasal sinuses. PMID- 26867527 TI - Characterizing airflow profile in the postoperative maxillary sinus by using computational fluid dynamics modeling: A pilot study. AB - BACKGROUND: Maxillary antrostomy is commonly performed during endoscopic sinus surgery. Little is known about the association surrounding recalcitrant maxillary sinusitis, antrostomy size, and intranasal airflow changes. Furthermore, the interaction between sinus mucosa and airflow is poorly understood. This study used computational fluid dynamics (CFD) modeling to investigate postoperative airflow characteristics between diseased and nondiseased maxillary sinuses in subjects with recurrent disease. METHODS: A retrospective review of patients from a tertiary-level academic rhinology practice was performed. Seven subjects with endoscopic evidence of postoperative maxillary sinus disease that presented as chronic unilateral crusting at least 1 year after bilateral maxillary antrostomies were selected. A three-dimensional model of each subject's sinonasal cavity was created from postoperative computed tomographies and used for CFD analysis. RESULTS: Although the variables investigated between diseased and nondiseased sides were not statistically significant, the diseased side in six subjects had a smaller antrostomy, and five of these subjects had both reduced nasal unilateral airflow and increased unilateral nasal resistance on the diseased side. The ratio of posterior wall shear stress (WSS) of the maxillary sinus to the total WSS was higher on the diseased side in six subjects. Results also showed strong correlations between antrostomy and CFD variables on the diseased side than on the nondiseased side. CONCLUSION: This pilot study showed that the majority of the simulated sinonasal models exhibited common characteristics on the side with persistent disease, such as smaller antrostomy, reduced nasal airflow, increased nasal resistance, and increased posterior WSS. Although statistical significance was not established, this study provided preliminary insight into variables to consider in a larger cohort study. PMID- 26867530 TI - The role of allergen immunotherapy in the management of allergic rhinitis. AB - PURPOSE: To evaluate the role of allergen immunotherapy (AIT) in the treatment of allergic rhinitis (AR). METHOD: Individual studies, systematic reviews, and practice guidelines that included information on sublingual AIT (SLIT) and subcutaneous AIT (SCIT) in the treatment of AR were considered. RESULTS: AIT via the SLIT or SCIT route has been shown to be effective in treating AR symptoms with resultant improvements in overall quality of life, comorbid illnesses, and medication requirements. Persistent clinical benefits have been demonstrated years after AIT treatment discontinuation. AIT may prevent the progression of AR to asthma. In addition, studies that evaluated the pharmacoeconomics of AR treatment indicate that AIT may be more cost effective than pharmacotherapy. The AIT cost savings are likely underestimated in that few cost comparison studies considered AIT's long-term benefits or preventive effects. CONCLUSION: Multiple individual studies and systematic reviews provide strong evidence for the clinical effectiveness of AIT in the treatment of AR. Cost-effectiveness and disease modification are additional advantages of AIT compared with standard drug treatment in the management of AR. PMID- 26867531 TI - The Rhinitis Control Scoring System: Development and validation. AB - BACKGROUND: Allergic rhinitis is a common health problem that requires regular monitoring of symptoms to provide adequate treatment. There is a need to develop rhinitis control assessment tools that are meaningful and easy to interpret by both the patient and the practitioner. OBJECTIVE: To develop a simple, easy-to interpret instrument, the Rhinitis Control Scoring System (RCSS), for the assessment of rhinitis control, as a companion tool to the Asthma Control Scoring System previously validated. METHODS: After a literature review and based on the Allergic Rhinitis and its Impact on Asthma guidelines, allergic rhinitis control parameters were identified. The draft items were subjected to cognitive debriefing regarding instructions, wordings, and response options. The second version of the draft was then pretested and modified according to the results. The final draft of the RCSS, based on the intensity and frequency of symptoms, was then pilot tested with 50 subjects who had allergic rhinitis for validation of some psychometric properties. Each subject completed the RCSS in addition to other rhinitis instruments. They also had nasal peak inspiratory flow measurements. RESULTS: The RCSS showed good internal consistency (Cronbach alpha = 0.84). There was strong criterion validity between the RCSS scores and the other instruments. The discriminant validity demonstrated as mean RCSS scores differed significantly across groups of patients with different Total Nasal Symptom Score severity (F = 58.8, p < 0.0001). CONCLUSIONS: This pilot study showed that the RCSS is a simple tool to assess and quantify rhinitis control by using a percentage score. This questionnaire allows the quantification of rhinitis control and, therefore, may help guide therapeutic interventions. Combined with the Asthma Control Scoring System, it can provide a global assessment of rhinitis and asthma control. Clinical Trial number NCT00967967. PMID- 26867529 TI - Relationships among allergic rhinitis, asthma, and chronic rhinosinusitis. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a common disease in the United States. There are a significant number of patients with CRS who are refractory to standard medical and surgical therapy. Many of these patients also have comorbid allergic rhinitis (AR) and asthma, although the underlying pathophysiology that connects these three conditions remains unclear. OBJECTIVE: The goal of this article is to review the relationships among CRS, AR and asthma. METHODS: Scientific literature that addresses the prevalence of AR and asthma in CRS populations, the effect of AR and asthma on CRS disease severity, and whether treatment of AR and asthma can affect CRS outcomes was reviewed. RESULTS: The literature supports the relationship between AR and CRS, but there is no direct evidence of causality the between the two conditions. There is a high prevalence of CRS in patients with asthma and the presence of CRS is associated with worse asthma outcomes. There is weak evidence that treatment of CRS may improve asthma outcomes. Targeting type 2 inflammation via biologics is being investigated in the treatment of asthma and CRS. CONCLUSION: AR, asthma, and CRS are closed related and understanding the associations among these comorbid diseases will have significant clinical implication. PMID- 26867533 TI - Neuron-specific enolase in nasal secretions as a novel biomarker of olfactory dysfunction in chronic rhinosinusitis. AB - BACKGROUND: Olfactory dysfunction is a diagnostic criterion for chronic rhinosinusitis (CRS). During chronic inflammation and olfactory neuronal damage in CRS, it is likely that neuron-specific enolase (NSE) can leak into nasal secretions (NS) and serum. Therefore, we postulated that NSE levels in NS and in circulation may be indicative of olfactory dysfunction in CRS. OBJECTIVE: To evaluate the relationship between the NS and serum concentrations of NSE with olfactory dysfunction in subjects with CRS. METHODS: The patients with CRS were classified into two groups, depending on the presence of polyps: CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). A group of age- and sex matched healthy volunteers served as controls. Olfactory function assessment was performed by using Sniffin' Sticks. NSE concentrations in serum and NS were analyzed by using the enzyme immunometric assay kit specific for the gamma subunit. RESULTS: The study included 46 patients with CRSsNP, 25 women (54.3%) and 21 men (45.7%), mean (standard deviation [SD]) age, 34.1 +/- 12.3 years; and 54 patients with CRSwNP, 24 women (44.4%) and 30 men (55.6%), mean (SD) age, 37.9 +/- 17.5 years. A group of 40 healthy volunteers who were matched for age and sex served as controls. Significantly higher serum and NS levels of NSE were measured in patients with CRS compared with healthy controls (p < 0.001). In the CRSwNP group, both mean (SD) serum (83.5 +/- 37.6 ng/mL) and mean (SD) NS (6.1 +/- 2.3 ng/mL) levels of NSE were significantly higher than in the CRSsNP group (46.4 +/- 7.3 ng/mL [p < 0.001] and 1.7 +/- 0.5 ng/mL [p < 0.001], respectively). In both the CRSsNP and CRSwNP groups (but not in the healthy controls), significant negative correlations between NS NSE levels and TDI scores (r = -0.63, p < 0.001 for the CRSwNP group, and r = -0.51, p < 0.001 for CRSsNP group) were observed, which meant that higher NSE was associated with worse olfactory function. CONCLUSIONS: The study demonstrated a contribution of CRS to NSE and olfactory dysfunction. PMID- 26867532 TI - Correlation of skin test results and specific immunoglobulin E blood levels with nasal provocation testing for house-dust mite allergies. AB - BACKGROUND: Allergen-specific immunotherapy for house-dust mite (HDM) allergies is associated with lower success rates when compared with similar treatments for other inhalant allergens, such as grass or birch. One reason might be the greater difficulty in diagnosing patients with assumed HDM allergies because symptoms occur perennially and may differ from those of a conventional allergic rhinitis. OBJECTIVE: The aim of the study was to compare the different methods of diagnosis in patients with assumed HDM allergy. METHODS: We performed a retrospective analysis of nasal provocation tests (NPT) from patients (n = 161) evaluated for Dermatophagoides pteronyssinus (n = 127) and Dermatophagoides farinae (n = 104) allergies, and compared the results with other allergen testing methods (skin prick test [SPT], intracutaneous test, and allergen specific immunoglobulin E levels [sIgE] to detect sensitization). Receiver operating characteristic curves were used for the analyses and the areas under the curve were calculated. RESULTS: For D. pteronyssinus and D. farinae, 86 and 70 complete data files, respectively, were available. For both tested HDMs, the results of the receiver operating characteristic curves showed a significant correlation for SPT and sIgE, with the results of the NPT (area under the curve, 0.742 to 0.763) but not for the intracutaneous test. In patients with a positive SPT (>=3 mm), an allergy was confirmed by the NPT in 69% of cases for D. pteronyssinus and 71% for D. farinae. A positive sIgE result (ImmunoCAP class of >=2) was verified by the NPT in 69% of cases (D. pteronyssinus) and 70% (D. farinae). CONCLUSION: The predictability value for a positive NPT result is best for SPT and sIgE. Nevertheless, even if the results of both test systems are combined, the positive predictive value that was achieved was only 0.77 for D. pteronyssinus and 0.69 for D. farinae. Therefore, in patients eligible for immunotherapy for HDM, an NPT should be performed before the start of the therapy to verify a clinically relevant allergy. PMID- 26867534 TI - Indications and outcomes for Draf IIB frontal sinus surgery. AB - BACKGROUND: Extended frontal surgery techniques are often required when maximal medical therapy and standard endoscopic surgical approaches fail in patients. Although outcomes of the Draf III (modified Lothrop) procedure have been widely reported, postoperative outcomes and indications for the Draf IIB frontal sinusotomy have been relatively underreported. We presented our institution's experience with the Draf IIB procedure. METHODS: Patients who underwent the Draf IIB frontal sinusotomy between 2007 and 2012 were identified by retrospective chart review. Data collected included demographics, imaging, sinus patency, and Sino-nasal Outcome Test 20 scores. RESULTS: A total of 22 Draf IIB frontal sinusotomies were performed in 18 patients. Thirteen of eighteen patients had previous frontal sinus surgery. The most common indications for the extended approach were chronic frontal sinusitis due to lateralized middle turbinate remnant (8 patients), mucocele (6), postoperative synechiae (5), and frontal sinus mass (3). Sinus ostium patency was maintained in 20 of 22 sinuses over an average follow-up period of 16.2 months. No complications were reported. CONCLUSIONS: The Draf IIB frontal sinusotomy is a relatively safe procedure, with multiple indications. Long-term sinus ostium patency was maintained in >90% of operated sinuses, which indicated that the Draf IIB procedure may present an acceptable alternative to more aggressive extended frontal sinus approaches in selected patients. PMID- 26867536 TI - Improved pregnancy outcomes with increasing antiretroviral coverage in South Africa. AB - BACKGROUND: Universal multi drug antiretroviral treatment in pregnancy is a global priority in our bid to eliminate paediatric HIV infections although few studies have documented the impact of antiretroviral coverage on overall pregnancy outcomes. METHODS: We conducted a maternity audit at a large regional hospital in South Africa during July-December 2011 and January-June 2014 with an aim to determine an association between pregnancy outcomes and the ARV treatment guidelines implemented during those specific periods. During 2011, women received either Zidovudine/sd Nevirapine or Stavudine/Lamivudine/Nevirapine if CD4+ count was < 350 cells/ml. During 2014, all HIV positive pregnant women were eligible for a fixed dose combination (FDC) of triple ARVs (Tenofovir/Emtracitabine/Efavirenz). RESULTS: In 2011, 622 (35.9%) of 1732 HIV positive pregnant women received triple antiretrovirals (D4T/3TC/NVP) and in 2014, 2104 (94.8%) of 2219 HIV positive pregnant women received the fixed dose combination (TDF/FTC/EFV). We observed a reduction in the proportion of unregistered pregnancies, caesarean delivery rate, still birth rate, very low birth weight rate, and very premature delivery rate in 2014. In a bivariate analysis of all 9,847 deliveries, unregistered pregnancies (2.2%) and HIV infection (37.8%) remained significant risk factors for SB(OR 6.36 and 1.43 respectively), PTD(OR 4.23 and 1.26 respectively),LBW (OR 4.07 and 1.26 respectively) and SGA(OR 2.17 and 1.151 respectively). In a multivariable analysis of HIV positive women only, having received AZT/NVP or D4T/3TC/NVP or EFV/TDF/FTC as opposed to not receiving any ARV was significantly associated with reduced odds of a SB (OR 0.08, 0.21 and 0.18 respectively), PTD (OR 0.52, 0.68 and 0.56 respectively) and LBW(0.37, 0.61 and 0.52 respectively). CONCLUSION: An improvement in birth outcomes is likely associated with the increased coverage of triple antiretroviral treatment for pregnant women. And untreated HIV infected women and women who do not seek antenatal care should be considered most at risk for poor birth outcomes. PMID- 26867537 TI - Outcome of Hepatitis B Virus Infection After Living-Donor Liver Transplant: A Single-center Experience Over 20 Years. AB - OBJECTIVES: Despite living-donor liver transplant being a life-saving therapy for patients with hepatitis B virus with or without hepatocellular carcinoma, outcomes for patients with these diseases are worse. Hepatitis B virus recurrence or relapse of hepatocellular carcinoma can result in subsequent graft loss or patient death. In this study, we discuss the postoperative outcomes of patients with hepatitis B virus infection after living-donor liver transplant. MATERIALS AND METHODS: We retrospectively analyzed 125 patients with hepatitis B virus related end-stage liver disease, comparing results with 1228 control patients who had other pathologies, including hepatitis C virus, combined hepatitis B virus and hepatitis C virus, and neither virus. RESULTS: Survival rates of patients with hepatitis B virus did not differ from the control groups (P > .05). Patients with concurrent hepatitis B virus and hepatocellular carcinoma were significantly older (P < .0001), had critical status (P < .0001), had chronic underlying pathology (P = .001), lower graft-to-recipient body weight ratio (P = .047), needed more intraoperative plasma transfusion, and experienced more rejection episodes than those without hepatocellular carcinoma. Of interest, in 5 patients who had hepatitis B virus recurrence after living-donor liver transplant, Model for End-Stage Liver Disease score was significantly higher than those who did not have recurrence (P = .015). In addition, 2 patients had hepatocellular carcinoma recurrence in the form of peritoneal metastasis, with both patients having high preoperative alpha-fetoprotein levels. CONCLUSIONS: Our study provides details on long-term outcomes of patients with hepatitis B virus infection who had undergone living-donor liver transplant. Based on our results, we suggest that prolonged antiviral prophylactic therapy in the form of hepatitis B immunoglobulin with either lamivudine or entecavir be considered for patients who associated with risk factors to prevent postoperative recurrence. PMID- 26867539 TI - Nocardioides zeicaulis sp. nov., an endophyte actinobacterium of maize. AB - A Gram-stain-positive, aerobic organism was isolated as an endophyte from the stem tissue of healthy maize (Zea mays) and investigated in detail for its taxonomic position. On the basis of the 16S rRNA gene sequence analysis, strain JM-601T was shown to be most closely related to Nocardioides alpinus (98.3%), and Nocardioides ganghwensis (98.0%). The 16S rRNA gene sequence similarity to all other species of the genus Nocardioides was <= 98.0%. The diagnostic diamino acid of the peptidoglycan was ll-diaminopimelic acid. The major quinone of strain JM 601T was menaquinone MK-8(H4). The polar lipid profile revealed the major components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, phosphatidylcholine and an unidentified phospholipid. The polyamine pattern contained predominantly spermine and moderate amounts of spermidine. In the fatty acid profile, iso-C16:0, C17:1omega8c and 10-methyl C17:0 were present in major amounts. All these data support the allocation of the strain to the genus Nocardioides. The results of physiological and biochemical characterization allow in addition a phenotypic differentiation of strain JM-601T from N. alpinus and N. ganghwensis. Strain JM-601T represents a novel species of the genus Nocardioides, for which we propose the name Nocardioides zeicaulis sp. nov., with JM-601T (=CCM 8654T=CIP 110980T) as the type strain. PMID- 26867538 TI - Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury After Intracerebral Hemorrhage in Mice. AB - Intracerebral hemorrhage (ICH) is a severe form of stroke with substantial public health impact. Notably, there is no effective treatment for ICH. Given the role of transcription factor Nrf2 (NF-E2-related factor 2) in antioxidant signaling, herein, we tested the efficacy of tert-butylhydroquinone (TBHQ), a selective inducer of Nrf2 in a preclinical model of ICH. Male CD1 mice were subjected to experimental intracerebral hemorrhage and administered intraperitoneally with TBHQ. The administration of TBHQ enhanced the DNA-binding activity of Nrf2 in the brain and reduced oxidative brain damage in comparison to vehicle-treated ICH. In addition, TBHQ treatment reduced microglial activation with concomitant reduction in the release of proinflammatory cytokine interleukin-1beta (IL-1 beta). Furthermore, TBHQ treatment attenuated neurodegeneration and improved neurological outcomes after ICH. Altogether, the data demonstrate the efficacy of post-injury administration of TBHQ in attenuating acute neurological injury after ICH. PMID- 26867540 TI - Inequalities in utilization of maternal and child health services in Ethiopia: the role of primary health care. AB - BACKGROUND: Health systems aim to narrow inequality in access to health care across socioeconomic groups and area of residency. However, in low-income countries, studies are lacking that systematically monitor and evaluate health programs with regard to their effect on specific inequalities. We aimed to measure changes in inequality in access to maternal and child health (MCH) interventions and the effect of Primary Health Care (PHC) facilities expansion on the inequality in access to care in Ethiopia. METHODS: The Demographic and Health Survey datasets from Ethiopia (2005 and 2011) were used. We calculated changes in utilization of MCH interventions and child morbidity. Concentration and horizontal inequity indices were estimated. Decomposition analysis was used to calculate the contribution of each determinant to the concentration index. RESULTS: Between 2005 and 2011, improvements in aggregate coverage have been observed for MCH interventions in Ethiopia. Wealth-related inequality has remained persistently high in all surveys. Socioeconomic factors were the main predictors of differences in maternal and child health services utilization and child health outcome. Utilization of primary care facilities for selected maternal and child health interventions have shown marked pro-poor improvement over the period 2005-2011. CONCLUSIONS: Our findings suggest that expansion of PHC facilities in Ethiopia might have an important role in narrowing the urban rural and rich-poor gaps in health service utilization for selected MCH interventions. PMID- 26867542 TI - Home Non Invasive Ventilation (NIV) treatment for COPD patients with a history of NIV-treated exacerbation; a randomized, controlled, multi-center study. AB - BACKGROUND: In chronic obstructive pulmonary disease, the prognosis for patients who have survived an episode of acute hypercapnic respiratory failure due to an exacerbation is poor. Despite being shown to improve survival and quality-of-life in stable patients with chronic hypercapnic respiratory failure, long-term noninvasive ventilation is controversial in unstable patients with frequent exacerbations, complicated by acute hypercapnic respiratory failure. In an uncontrolled group of patients with previous episodes of acute hypercapnic respiratory failure, treated with noninvasive ventilation, we have been able to reduce mortality and the number of repeat respiratory failure and readmissions by continuing the acute noninvasive ventilatory therapy as a long-term therapy. METHODS: Multi-center open label randomized controlled trial of 150 patients having survived an admission with noninvasive ventilatory treatment of acute hypercapnic respiratory failure due chronic obstructive pulmonary disease. The included patients are randomized to usual care or to continuing the acute noninvasive ventilation as a long-term therapy, both with a one-year follow-up period. The primary endpoint is time to death or repeat acute hypercapnic respiratory failure; secondary endpoints are one-year mortality, number of readmissions and repeat acute hypercapnic respiratory failure, exacerbations, dyspnea, quality of life, sleep quality, lung function, and arterial gases. DISCUSSION: Though previous studies of long-term noninvasive ventilation have shown conflicting results, we believe the treatment can reduce mortality and readmissions when applied in patients with previous need of acute ventilatory support, regardless of persistent hypercapnia. TRIAL REGISTRATION: clinicaltrials.org: NCT01513655 16-Jan-2012. PMID- 26867541 TI - Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial. AB - BACKGROUND: Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the "cross-transfer" of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes). METHODS AND STUDY DESIGN: This is a single-blinded, single-site, randomized controlled trial. A minimum of 32 (and up to 40) subjects aged 18 to 50 years with recurrent low back pain and poor trunk extensor muscle endurance will be recruited, enrolled and randomized. After completion of baseline assessments, participants will be randomized in a 1:1 ratio to receive a 10-week resistance exercise training program with blood flow restriction (BFR exercise group) or without blood flow restriction (control exercise group). Repeat assessments will be taken immediately post intervention and at 12 weeks after the completion of the exercise program. Furthermore, once every 4 weeks during a 36-week follow-up period, participants will be asked to rate their perceived disability and back pain over the past 14 days. DISCUSSION: This study will examine the potential for blood flow restricted exercise applied to appendicular muscles to result in a "cross-transfer" of therapeutic effect to the lumbar musculature in individuals with low back pain. The results of this study will provide important insights into the effectiveness of this novel exercise modality, which could potentially provide the foundation for a cost-effective and easy-to-implement rehabilitation strategy to induce muscle adaptation in the absence of high mechanical and compressive loading on the spine. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (registration number: NCT02308189, date of registration: 2 December 2014). PMID- 26867543 TI - Scalable Expansion of Human Pluripotent Stem Cell-Derived Neural Progenitors in Stirred Suspension Bioreactor Under Xeno-free Condition. AB - Recent advances in neural differentiation technology have paved the way to generate clinical grade neural progenitor populations from human pluripotent stem cells. These cells are an excellent source for the production of neural cell based therapeutic products to treat incurable central nervous system disorders such as Parkinson's disease and spinal cord injuries. This progress can be complemented by the development of robust bioprocessing technologies for large scale expansion of clinical grade neural progenitors under GMP conditions for promising clinical use and drug discovery applications. Here, we describe a protocol for a robust, scalable expansion of human neural progenitor cells from pluripotent stem cells as 3D aggregates in a stirred suspension bioreactor. The use of this platform has resulted in easily expansion of neural progenitor cells for several passages with a fold increase of up to 4.2 over a period of 5 days compared to a maximum 1.5-2-fold increase in the adherent static culture over a 1 week period. In the bioreactor culture, these cells maintained self-renewal, karyotype stability, and cloning efficiency capabilities. This approach can be also used for human neural progenitor cells derived from other sources such as the human fetal brain. PMID- 26867545 TI - Building an Evidence Base for Effective Supervision Practices: An Analogue Experiment of Supervision to Increase EBT Fidelity. AB - Treatments that are efficacious in research trials perform less well under routine conditions; differences in supervision may be one contributing factor. This study compared the effect of supervision using active learning techniques (e.g. role play, corrective feedback) versus "supervision as usual" on therapist cognitive restructuring fidelity, overall CBT competence, and CBT expertise. Forty therapist trainees attended a training workshop and were randomized to supervision condition. Outcomes were assessed using behavioral rehearsals pre- and immediately post-training, and after three supervision meetings. EBT knowledge, attitudes, and fidelity improved for all participants post-training, but only the SUP+ group demonstrated improvement following supervision. PMID- 26867544 TI - Whole-Heart Construct Cultivation Under 3D Mechanical Stimulation of the Left Ventricle. AB - Today the concept of Whole-Heart Tissue Engineering represents one of the most promising approaches to the challenge of synthesizing functional myocardial tissue. At the current state of scientific and technological knowledge it is a principal task to transfer findings of several existing and widely investigated models to the process of whole-organ tissue engineering. Hereby, we present the first bioreactor system that allows the integrated 3D biomechanical stimulation of a whole-heart construct while allowing for simultaneous controlled perfusion of the coronary system. PMID- 26867546 TI - Atypical presentations of thrombotic thrombocytopenic purpura: a diagnostic role for ADAMTS13. AB - Thrombotic thrombocytopenic purpura (TTP) is an acute, life threatening disease. Only a minority of patients expresses the complete clinical presentation and unusual manifestations can occur. Demonstration of low activity levels of ADAMTS13 (<5 %) is highly specific for the diagnosis of TTP. This study reports a series of five cases of TTP presenting with a thrombotic event and no hematological findings. Detailed chart reviews on these patients were conducted. We identified two patients whose first attack of TTP presented as a thrombotic episode without microangiopathic hemolytic anemia and thrombocytopenia, only to be diagnosed as TTP days later, after the appearance of hematological signs. We also describe three cases of classical TTP relapsing atypically as cerebrovascular accidents without hematological signs. Low levels of ADAMTS13 activity were detected and facilitated the diagnosis. The neurological manifestations disappeared concurrent with normalization of ADAMTS13 activity level after plasma exchange. This study underscores the importance of having a high clinical suspicion of TTP in cases of thrombosis even without hematological abnormalities in patients with previous attacks of TTP. In this clinical scenario, measurement of ADAMTS13 activity is important for diagnosis and early administration of treatment. PMID- 26867547 TI - Predictors of postnatal mother-infant bonding: the role of antenatal bonding, maternal substance use and mental health. AB - The emotional bond that a mother feels towards her baby is critical to social, emotional and cognitive development. Maternal health and wellbeing through pregnancy and antenatal bonding also play a key role in determining bonding postnatally, but the extent to which these relationships may be disrupted by poor mental health or substance use is unclear. This study aimed to examine the extent to which mother-fetal bonding, substance use and mental health through pregnancy predicted postnatal mother-infant bonding at 8 weeks. Participants were 372 women recruited from three metropolitan hospitals in Australia. Data was collected during trimesters one, two and three of pregnancy and 8 weeks postnatal using the Maternal Antenatal Attachment Scale (MAAS), Maternal Postnatal Attachment Scale (MPAS), the Edinburgh Antenatal and Postnatal Depression Scale (EPDS), the Depression and Anxiety Scales (DASS-21), frequency and quantity of substance use (caffeine, alcohol and tobacco) as well as a range of demographic and postnatal information. Higher antenatal bonding predicted higher postnatal bonding at all pregnancy time-points in a fully adjusted regression model. Maternal depressive symptoms in trimesters two and three and stress in trimester two were inversely related to poorer mother-infant bonding 8 weeks postnatally. This study extends previous work on the mother's felt bond to her developing child by drawing on a large sample of women and documenting the pattern of this bond at three time points in pregnancy and at 8 weeks postnatally. Utilising multiple antenatal waves allowed precision in isolating the relationships in pregnancy and at key intervention points. Investigating methods to enhance bonding and intervene in pregnancy is needed. It is also important to assess maternal mental health through pregnancy. PMID- 26867548 TI - Clinical Outcomes of Endoscopic Submucosal Dissection for Superficial Esophageal Squamous Neoplasms. AB - BACKGROUND/AIMS: Endoscopic treatment has been broadly applied to superficial esophageal neoplasms. Endoscopic submucosal dissection (ESD) allows for high rates of en bloc resection, precise histological assessment, and low rates of local recurrence. The aim of this study was to evaluate the outcomes of ESD for superficial esophageal neoplasms. METHODS: We retrospectively reviewed 36 esophageal ESDs for superficial squamous neoplasms in 32 patients between March 2009 and August 2014 at Gangnam Severance Hospital. RESULTS: The median patient age was 64 years, and 30 men were included. The indications were early squamous cell carcinoma in 26 lesions, adenoma with high-grade dysplasia in five lesions, and low-grade dysplasia in five lesions. The en bloc resection and R0 resection rates were 97.2% (35 of 36) and 91.7% (33 of 36), respectively. Microperforation and post-ESD bleeding occurred in 5.6% (2 of 36) and 5.6% (2 of 36), respectively. Post-ESD esophageal strictures developed in five patients (13.9%). Five patients (15.6%) had an additional treatment after ESD (concurrent chemoradiation therapy in three, radiation therapy in one, and surgery in one patient). There was no disease-specific mortality during the median follow-up of 31 months. CONCLUSIONS: Favorable clinical outcomes were observed in ESD for superficial esophageal squamous neoplasms. Esophageal ESD could be a good treatment option in terms of efficacy and safety. PMID- 26867549 TI - Obesity and Cecal Intubation Time. AB - BACKGROUND/AIMS: Obesity is a much-debated factor with conflicting evidence regarding its association with cecum intubation rates during colonoscopy. We aimed to identify the association between cecal intubation (CI) time and obesity by eliminating confounding factors. METHODS: A retrospective chart review of subjects undergoing outpatient colonoscopy was conducted. The population was categorized by sex and obesity (body mass index [BMI, kg/m(2)]: I, <24.9; II, 25 to 29.9; III, >=30). CI time was used as a marker for a difficult colonoscopy. Mean CI times (MCT) were compared for statistical significance using analysis of variance tests. RESULTS: A total of 926 subjects were included. Overall MCT was 15.7+/-7.9 minutes, and it was 15.9+/-7.9 and 15.5+/-7.9 minutes for men and women, respectively. MCT among women for BMI category I, II, and III was 14.4+/ 6.5, 15.5+/-8.3, and 16.2+/-8.1 minutes (p=0.55), whereas for men, it was 16.3+/ 8.9, 15.9+/-8.0, and 15.6+/-7.2 minutes (p=0.95), respectively. CONCLUSIONS: BMI had a positive association with CI time for women, but had a negative association with CI for men. PMID- 26867550 TI - Laterally Spreading Tumor of the Rectum Delineated with Linked Color Imaging Technology. PMID- 26867551 TI - Immunoglobulin G4-Related Inflammatory Pseudotumor Presenting as a Solitary Mass in the Stomach. AB - Immunoglobulin G4 (IgG4)-related disease (IgG4RD) is a relatively recently recognized entity that is histopathologically characterized by an extensive infiltration of lymphocytes and IgG4-positive plasma cells with dense fibrosis. IgG4RD is now known to affect any organ system, and a few cases of gastrointestinal lesions have also been reported. However, solitary IgG4RD of the stomach is still very rare. Furthermore, as it can mimic malignant conditions, it is important to recognize this disease to avoid unnecessary surgery. Herein, we present a case of IgG4RD presenting as an isolated subepithelial mass in the stomach. PMID- 26867552 TI - Endoscopic Electrosurgery in Patients with Cardiac Implantable Electronic Devices. AB - BACKGROUND/AIMS: Patients with cardiac implantable electronic devices (CIEDs) undergoing endoscopic electrosurgery (EE) are at a risk of electromagnetic interference (EMI). We aimed to analyze the effects of EE in CIED patients. METHODS: Patients with CIED who underwent EE procedures such as snare polypectomy, endoscopic submucosal dissection (ESD), and endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) were retrospectively analyzed. Postprocedural symptoms as well as demographic and outpatient follow-up data were reviewed through medical records. Electrical data, including preprocedural and postprocedural arrhythmia records, were reviewed through pacemaker interrogation, 24-hour Holter monitoring, or electrocardiogram. RESULTS: Fifty-nine procedures in 49 patients were analyzed. Fifty procedures were performed in 43 patients with a pacemaker, and nine were performed in six patients with an implantable cardioverter-defibrillator. There were one gastric and 44 colon snare polypectomies, five gastric and one colon ESDs, and eight ERCPs with EST. Fifty-five cases of electrical follow-up were noted, with two postprocedural changes not caused by EE. Thirty-one pacemaker interrogations had procedure recordings, with two cases of asymptomatic tachycardia. All patients were asymptomatic with no adverse events. CONCLUSIONS: Our study reports no adverse events from EE in patients with CIED, suggesting that this procedure is safe. However, because of the possibility of EMI, recommendations on EE should be followed. PMID- 26867553 TI - Asymptomatic Gastric Band Erosion Detected during Routine Gastroduodenoscopy. AB - The incidence of gastric band erosion has decreased to 1%. Gastric band erosion can manifest with various clinical symptoms, although some patients remain asymptomatic. We present a case of a mostly asymptomatic patient who was diagnosed with gastric band erosion during a routine health check-up. A 32-year old man without any underlying diseases except for non-alcoholic fatty liver underwent laparoscopic adjustable gastric band surgery in 2010. He had no significant complications postoperatively. He underwent routine health check-ups with near-normal gastroduodenoscopic findings through 2014. However, in 2015, routine gastroduodenoscopy showed that the gastric band had eroded into the stomach. His gastric band was removed laparoscopically, and the remaining gastric ulcer perforation was repaired using an omental patch. Due to the early diagnosis, the infection was not serious. The patient was discharged on postoperative day 3 with oral antibiotics. This patient was fortunately diagnosed early by virtue of a routine health check-up; thus, eliminating the possibility of serious complications. PMID- 26867554 TI - Quality of Life of Patients with Cancer: A Determinant of the Quality of Life of Their Family Caregivers. AB - Cancer disrupts the quality of life of both the patients and their family caregivers. This study attempted to explore the relationship between the quality of life of cancer patients and their family caregivers and to examine whether the quality of life, age, and gender of the patients contributed to the quality of life of their family caregivers. This correlational study involved 206 pairs of participants consisting of cancer patients and their corresponding family caregivers. The European Organization for the Treatment and Research of Quality of Life Questionnaire C-30 (version 3) was administered on the patients and the Caregiver Quality of Life-Cancer was administered on their family caregivers. The result revealed that social functioning, appetite loss, physical functioning, and gender of the patients contributed significantly to the quality of life of their family caregivers. Implications, shortcomings, and future directions were discussed. PMID- 26867556 TI - Intelligent Agent Transparency in Human-Agent Teaming for Multi-UxV Management. AB - OBJECTIVE: We investigated the effects of level of agent transparency on operator performance, trust, and workload in a context of human-agent teaming for multirobot management. BACKGROUND: Participants played the role of a heterogeneous unmanned vehicle (UxV) operator and were instructed to complete various missions by giving orders to UxVs through a computer interface. An intelligent agent (IA) assisted the participant by recommending two plans-a top recommendation and a secondary recommendation-for every mission. METHOD: A within subjects design with three levels of agent transparency was employed in the present experiment. There were eight missions in each of three experimental blocks, grouped by level of transparency. During each experimental block, the IA was incorrect three out of eight times due to external information (e.g., commander's intent and intelligence). Operator performance, trust, workload, and usability data were collected. RESULTS: Results indicate that operator performance, trust, and perceived usability increased as a function of transparency level. Subjective and objective workload data indicate that participants' workload did not increase as a function of transparency. Furthermore, response time did not increase as a function of transparency. CONCLUSION: Unlike previous research, which showed that increased transparency resulted in increased performance and trust calibration at the cost of greater workload and longer response time, our results support the benefits of transparency for performance effectiveness without additional costs. APPLICATION: The current results will facilitate the implementation of IAs in military settings and will provide useful data to the design of heterogeneous UxV teams. PMID- 26867557 TI - Policy layers delay funding of innovative care deal for elderly people, conference hears. PMID- 26867555 TI - Derivative Quotient Spectrophotometry and an Eco-Friendly Micellar Chromatographic Approach with Time-Programmed UV-Detection for the Separation of Two Fluoroquinolones and Phenazopyridine. AB - In this study, two analytical approaches were exploited for the resolution of binary mixtures of ciprofloxacin HCl (CIP) or norfloxacin (NOR) and phenazopyridine HCl (PHZ). In the first approach, the amplitudes of the first derivative of the ratio spectra were measured at 267 or 287 nm for CIP and at 268 or 291 nm for NOR. PHZ could be directly determined in the presence of CIP or NOR at 405 nm. The calibration graphs were rectilinear over the ranges of 1.0-16.0 ug/mL for CIP or NOR and 1.0-10.0 ug/mL for PHZ. In the second approach, an accurate, reliable and environmentally nontoxic micellar liquid chromatographic (MLC) method was developed. A good chromatographic separation was achieved using a 150 mm * 4.6 mm i.d., 5 um particle size Spherisorb ODS-2 column. Eco-friendly mobile phase containing 0.12 M sodium dodecyl sulphate, 0.3% triethylamine and 6%n-butanol in 0.02 M orthophosphoric acid of pH 3.0 was pumped at a flow rate of 1 mL/min. Time programmed UV-detection was applied to allow sensitive determination of the studied drugs. The analytes were eluted without interferences in <10 min. Methocarbamol was used as an internal standard. The MLC method was found to be rectilinear over the concentration range of 0.5-20.0 MUg/mL for CIP, NOR or PHZ. These optimized and validated methods were successfully applied for the simultaneous analysis of the studied drugs in their synthetic mixtures and co-formulated tablets. Moreover, the second method was further extended to the determination of these drugs in human urine with direct injection and without any pretreatment. PMID- 26867558 TI - Contractures and muscle disease. AB - Contractures are one of a handful of signs in muscle disease, besides weakness and its distribution, whose presence can help guide us diagnostically, a welcome star on the horizon. Contractures are associated with several myopathies, some with important cardiac manifestations, and consequently are important to recognise; their presence may also provide us with a potential satisfying 'penny dropping' diagnostic moment. PMID- 26867560 TI - Selenium Supplementation for Prevention of Late-Onset Sepsis in Very Low Birth Weight Preterm Neonates. AB - BACKGROUND: Neonatal mortality continues to be a significant problem in the Indian setting, especially in very low birth weight (VLBW) neonates. Selenium (Se) has been shown to possess antioxidant properties, and some recent studies have shown a reduction in the sepsis-attributable neonatal mortality with its use. India is a Se-deficient country. Blood Se concentrations in newborns are lower than those of their mothers and lower still in preterm infants. OBJECTIVE: To evaluate the efficacy of Se in preventing the first episode of late-onset sepsis in VLBW preterm neonates. METHODS: Ninety neonates weighing <1500 g and period of gestation <32 weeks, asymptomatic at birth and admitted to the neonatal intensive-care unit (NICU) in the first 12 h of birth with no maternal risk factors for sepsis were analyzed in the study. Se or placebo was supplemented orally once daily from 1st to 28th day of life to the test (n = 45) or control (n = 45) groups, respectively, followed by daily clinical assessment for signs or symptoms of sepsis in the hospital and weekly after discharge. RESULTS: Preterm VLBW neonates (mean birth weight 1464.22 +/- 50.14 g and mean gestational age 221.75 +/- 4 days) are Se deficient at birth, with mean (SD) Se levels 31.1 +/- 14.8 ug/l. Se supplementation at 10 ug/day increased serum Se levels significantly (63.9 +/- 13.9 ug/l on Day 28 in Se vs. 40.9 +/- 17.3 on Day 28 in placebo; p < 0.01). The incidence of the first episode of culture-proven late onset sepsis was significantly lower in the Se than in the placebo group. [0/45 (0%) in Se vs. 6/45 (13.3%) in placebo; p = 0.033]. The incidence of probable sepsis was found to be significantly lower in the Se group [7/45 (15.55%)] than in the placebo [16/45 (35.55%)]; p = 0.02. The total incidence of any late-onset sepsis (i.e. culture-proven plus probable sepsis) was also significantly reduced by Se supplementation. [7/45 (15.55%) in Se vs. 22/45 (48.88%) in placebo; p = 0.001]. CONCLUSION: Preterm VLBW neonates are Se deficient at birth. Se supplementation at 10 ug/day resulted in getting the Se levels into the acceptable normal level and reduced the incidence of the first episode of late onset sepsis in these neonates. PMID- 26867561 TI - Effects of Kangaroo Care on Neonatal Pain in South Korea. AB - Blood sampling for a newborn screening test is necessary for all neonates in South Korea. During the heel stick, an appropriate intervention should be implemented to reduce neonatal pain. This study was conducted to identify the effectiveness of kangaroo care (KC), skin contact with the mother, on pain relief during the neonatal heel stick. Twenty-six neonates undergoing KC and 30 control neonates at a university hospital participated in this study. Physiological responses of neonates, including heart rate, oxygen saturation, duration of crying and Premature Infant Pain Profile (PIPP) scores were measured and compared before, during and 1 min and 2 min after heel sticks. The heart rate of KC neonates was lower at both 1 and 2 min after sampling than those of the control group. Also, PIPP scores of KC neonates were significantly lower both during and after sampling. The duration of crying for KC neonates was around 10% of the duration of the control group. In conclusion, KC might be an effective intervention in a full-term nursery for neonatal pain management. PMID- 26867559 TI - Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy. AB - Background Intensive bimanual therapy can improve hand function in children with unilateral spastic cerebral palsy (USCP). We compared the effects of structured bimanual skill training versus unstructured bimanual practice on motor outcomes and motor map plasticity in children with USCP. Objective We hypothesized that structured skill training would produce greater motor map plasticity than unstructured practice. Methods Twenty children with USCP (average age 9.5; 12 males) received therapy in a day camp setting, 6 h/day, 5 days/week, for 3 weeks. In structured skill training (n = 10), children performed progressively more difficult movements and practiced functional goals. In unstructured practice (n = 10), children engaged in bimanual activities but did not practice skillful movements or functional goals. We used the Assisting Hand Assessment (AHA), Jebsen-Taylor Test of Hand Function (JTTHF), and Canadian Occupational Performance Measure (COPM) to measure hand function. We used single-pulse transcranial magnetic stimulation to map the representation of first dorsal interosseous and flexor carpi radialis muscles bilaterally. Results Both groups showed significant improvements in bimanual hand use (AHA; P < .05) and hand dexterity (JTTHF; P < .001). However, only the structured skill group showed increases in the size of the affected hand motor map and amplitudes of motor evoked potentials (P < .01). Most children who showed the most functional improvements (COPM) had the largest changes in map size. Conclusions These findings uncover a dichotomy of plasticity: the unstructured practice group improved hand function but did not show changes in motor maps. Skill training is important for driving motor cortex plasticity in children with USCP. PMID- 26867562 TI - Agaro-oligosaccharides: a new frontier in the fight against colon cancer? PMID- 26867563 TI - Lactobacillus acidophilus stimulates intestinal P-glycoprotein expression via a c Fos/c-Jun-dependent mechanism in intestinal epithelial cells. AB - Our previous studies showed that Lactobacillus acidophilus (LA) culture supernatant (CS) increased P-glycoprotein [Pgp/multidrug resistance 1 (MDR1)] function, expression, and promoter activity in Caco-2 cells. The current studies were designed to elucidate the molecular mechanisms mediating the stimulatory effects of LA CS on Pgp promoter activity. Deletion analysis indicated that the LA CS response element(s) is located in the -172/+428-bp region, and sequence analysis of this region revealed three potential binding sites for c-Fos or c Jun: proximal activating protein (AP) 1a (-119/-98 bp), distal AP1b (-99/-78 bp), and AP1c (+175/+196 bp). LA CS (24 h) showed an approximately twofold increase in the protein expression of c-Fos and c-Jun in Caco-2 cells. Electrophoretic mobility shift assay showed that LA CS markedly increased the binding of Caco-2 nuclear proteins to AP1a and AP1b, but not AP1c. The DNA-protein complex was completely eliminated by c-Fos antibody, while c-Jun antibody partially eliminated the complex. Chromatin immunoprecipitation analysis also showed that LA CS enhanced the association of c-Fos and c-Jun (by ~4- and 1.5-fold, respectively) with endogenous Pgp promoter in Caco-2 cells (p-172/+1). Interestingly, overexpression of c-Fos or c-Jun activated Pgp promoter by nearly twofold each. This increase was further enhanced (~14-fold) when c-Fos and c-Jun were simultaneously overexpressed, suggesting that the presence of one of these transcription factors potentiates the effect of the other. These studies, for the first time, provide evidence for the involvement of c-Fos/c-Jun in stimulation of Pgp gene expression by LA CS in the human intestine. PMID- 26867564 TI - Nuclear factor-kappaB regulates the expression of multiple genes encoding liver transport proteins. AB - In this study we identified the mechanisms underlying the inhibitory effects of NF-kappaB on the expression of genes encoding multiple liver transport proteins. Well-conserved NF-kappaB binding sites were found in the promoters of farnesoid X receptor (FXR)-target genes. An electromobility shift assay (EMSA) demonstrated the specific interaction between the NF-kappaB p65 protein and a (32)P-labeled BSEP NF-kappaB response element (NF-kappaBE). Chromatin immunoprecipitation (ChIP) analysis confirmed binding of NF-kappaB p65 to the BSEP locus but not the FXRE in vitro. NF-kappaB p65 overexpression in Huh-7 cells markedly repressed FXR/RXR transactivation of the BSEP, ABCG5/G8, MRP2, and FXR promoters, which was totally reversed by expression of the IkappaBalpha super-repressor. NF-kappaB interacted directly with FXR on coimmunoprecipitation, suggesting another level for the inhibitory effects of NF-kappaB on FXR-target genes. In vivo ChIP analysis with liver nuclei obtained from mice after 3 days of common bile duct ligation (BDL) or 6 h post-lipopolysaccharide (LPS) injection showed a markedly increased recruitment of NF-kappaB p65 to the Bsep promoter compared with controls. There was also increased recruitment of the corepressor silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and histone deacetylase (HDAC)3 and HDAC2 to the NF-kappaB sites. We also found that NF kappaB p65 was recruited to NF-kappaB binding sites in the promoters of organic solute transporter, OSTalpha and OSTbeta, and unexpectedly activated rather than repressed gene expression. In mouse liver after BDL NF-kappaB recruitment to Ostalpha and Ostbeta promoters was associated with increased binding of the potent coactivator cAMP response element binding protein (CREB)-binding protein (CBP)/p300 to the NF-kappaBE and depletion of CBP/p300 at the FXR element. Overall, these studies demonstrate a novel role for NF-kappaB in adaptation to obstructive and LPS-induced cholestasis acting through recruitment to specific NF kappaB binding sites in the promoters of FXR-target genes and possibly through direct interaction with FXR. PMID- 26867565 TI - TAM receptor tyrosine kinase function and the immunopathology of liver disease. AB - Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology. PMID- 26867566 TI - Deletion of Na+/H+ exchanger regulatory factor 2 represses colon cancer progress by suppression of Stat3 and CD24. AB - The Na(+)/H(+) exchanger regulatory factor (NHERF) family of proteins is scaffolds that orchestrate interaction of receptors and cellular proteins. Previous studies have shown that NHERF1 functions as a tumor suppressor. The goal of this study is to determine whether the loss of NHERF2 alters colorectal cancer (CRC) progress. We found that NHERF2 expression is elevated in advanced-stage CRC. Knockdown of NHERF2 decreased cancer cell proliferation in vitro and in a mouse xenograft tumor model. In addition, deletion of NHERF2 in Apc(Min/+) mice resulted in decreased tumor growth in Apc(Min/+) mice and increased lifespan. Blocking NHERF2 interaction with a small peptide designed to bind the second PDZ domain of NHERF2 attenuated cancer cell proliferation. Although NHERF2 is known to facilitate the effects of lysophosphatidic acid receptor 2 (LPA2), transcriptome analysis of xenograft tumors revealed that NHERF2-dependent genes largely differ from LPA2-regulated genes. Activation of beta-catenin and ERK1/2 was mitigated in Apc(Min/+);Nherf2(-/-) adenomas. Moreover, Stat3 phosphorylation and CD24 expression levels were suppressed in Apc(Min/+);Nherf2(-/-) adenomas. Consistently, NHERF2 knockdown attenuated Stat3 activation and CD24 expression in colon cancer cells. Interestingly, CD24 was important in the maintenance of Stat3 phosphorylation, whereas NHERF2-dependent increase in CD24 expression was blocked by inhibition of Stat3, suggesting that NHERF2 regulates Stat3 phosphorylation through a positive feedback mechanism between Stat3 and CD24. In summary, this study identifies NHERF2 as a novel oncogenic protein and a potential target for cancer treatment. NHERF2 potentiates the oncogenic effects in part by regulation of Stat3 and CD24. PMID- 26867567 TI - HOX transcription factors are potential targets and markers in malignant mesothelioma. AB - BACKGROUND: The HOX genes are a family of homeodomain-containing transcription factors that determine cellular identity during development and which are dys regulated in some cancers. In this study we examined the expression and oncogenic function of HOX genes in mesothelioma, a cancer arising from the pleura or peritoneum which is associated with exposure to asbestos. METHODS: We tested the sensitivity of the mesothelioma-derived lines MSTO-211H, NCI-H28, NCI-H2052, and NCI-H226 to HXR9, a peptide antagonist of HOX protein binding to its PBX co factor. Apoptosis was measured using a FACS-based assay with Annexin, and HOX gene expression profiles were established using RT-QPCR on RNA extracted from cell lines and primary mesotheliomas. The in vivo efficacy of HXR9 was tested in a mouse MSTO-211H flank tumor xenograft model. RESULTS: We show that HOX genes are significantly dysregulated in malignant mesothelioma. Targeting HOX genes with HXR9 caused apoptotic cell death in all of the mesothelioma-derived cell lines, and prevented the growth of mesothelioma tumors in a mouse xenograft model. Furthermore, the sensitivity of these lines to HXR9 correlated with the relative expression of HOX genes that have either an oncogenic or tumor suppressive function in cancer. The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival. CONCLUSION: HOX genes are a potential therapeutic target in mesothelioma, and HOXB4 expression correlates with overall survival. PMID- 26867568 TI - Generation and filtering of gene expression noise by the bacterial cell cycle. AB - BACKGROUND: Gene expression within cells is known to fluctuate stochastically in time. However, the origins of gene expression noise remain incompletely understood. The bacterial cell cycle has been suggested as one source, involving chromosome replication, exponential volume growth, and various other changes in cellular composition. Elucidating how these factors give rise to expression variations is important to models of cellular homeostasis, fidelity of signal transmission, and cell-fate decisions. RESULTS: Using single-cell time-lapse microscopy, we measured cellular growth as well as fluctuations in the expression rate of a fluorescent protein and its concentration. We found that, within the population, the mean expression rate doubles throughout the cell cycle with a characteristic cell cycle phase dependent shape which is different for slow and fast growth rates. At low growth rate, we find the mean expression rate was initially flat, and then rose approximately linearly by a factor two until the end of the cell cycle. The mean concentration fluctuated at low amplitude with sinusoidal-like dependence on cell cycle phase. Traces of individual cells were consistent with a sudden two-fold increase in expression rate, together with other non-cell cycle noise. A model was used to relate the findings and to explain the cell cycle-induced variations for different chromosomal positions. CONCLUSIONS: We found that the bacterial cell cycle contribution to expression noise consists of two parts: a deterministic oscillation in synchrony with the cell cycle and a stochastic component caused by variable timing of gene replication. Together, they cause half of the expression rate noise. Concentration fluctuations are partially suppressed by a noise cancelling mechanism that involves the exponential growth of cellular volume. A model explains how the functional form of the concentration oscillations depends on chromosome position. PMID- 26867569 TI - Analysis of mitochondrial DNA alteration in new phenotype ACOS. AB - BACKGROUND: Mitochondria contain their own DNA (MtDNA) that is very sensitive to oxidative stress and as a consequence could be damaged in quantity. Oxidative stress is largely recognized to play a key role in the pathogenesis of asthma and COPD and might have a role in the new intermediate phenotype ACOS (asthma-COPD overlap syndrome). The aim of this study was to investigate MtDNA alterations, as an expression of mitochondrial dysfunction, in ACOS and to verify whether they might help in the identification of this new phenotype and in its differentiation from asthma and COPD. METHODS: Ten (10) ACOS according to Spanish guidelines, 13 ACOS according to GINA guidelines, 13 COPD, 14 asthmatic patients and ten normal subjects were enrolled. They further underwent a blood, induced sputum and exhaled nitric oxide collection. Content of MtDNA and nuclear DNA (nDNA) were measured in the blood cells of patients by Real Time PCR. RESULTS: ACOS patients showed an increase of MtDNA/nDNA ratio. Dividing ACOS according to guidelines, those from the Spanish showed a higher value of MtDNA/nDNA compared to those from GINA/GOLD (92.69 +/- 7.31 vs 80.68 +/- 4.16). Spanish ACOS presented MtDNA/nDNA ratio closer to COPD than asthma. MtDNA was higher in asthmatic, COPD, GINA and Spanish ACOS patients compared to healthy subjects (73.30 +/- 4.47-137.0 +/- 19.45-80.68 +/- 4.16-92.69 +/- 7.31 vs 65.97 +/- 20.56). CONCLUSION: We found an increase of MtDNA/nDNA ratio in ACOS subjects that led us to conclude that there is presence of mitochondrial dysfunction in this disease, that makes it closer to COPD than to asthma. Although the MtDNA/nDNA ratio results are a useful marker for differential diagnosis from asthma, COPD and ACOS, further studies are needed to confirm the potentiality of MtDNA/nDNA ratio and to a better characterization of ACOS. PMID- 26867570 TI - 3D Polyaniline Architecture by Concurrent Inorganic and Organic Acid Doping for Superior and Robust High Rate Supercapacitor Performance. AB - A good high rate supercapacitor performance requires a fine control of morphological (surface area and pore size distribution) and electrical properties of the electrode materials. Polyaniline (PANI) is an interesting material in supercapacitor context because it stores energy Faradaically. However in conventional inorganic (e.g. HCl) acid doping, the conductivity is high but the morphological features are undesirable. On the other hand, in weak organic acid (e.g. phytic acid) doping, interesting and desirable 3D connected morphological features are attained but the conductivity is poorer. Here the synergy of the positive quality factors of these two acid doping approaches is realized by concurrent and optimized strong-inorganic (HCl) and weak-organic (phytic) acid doping, resulting in a molecular composite material that renders impressive and robust supercapacitor performance. Thus, a nearly constant high specific capacitance of 350 F g(-1) is realized for the optimised case of binary doping over the entire range of 1 A g(-1) to 40 A g(-1) with stability of 500 cycles at 40 A g(-1). Frequency dependant conductivity measurements show that the optimized co-doped case is more metallic than separately doped materials. This transport property emanates from the unique 3D single molecular character of such system. PMID- 26867571 TI - Pretransplant Stable Systolic Cardiac Functions Play an Important Role in Short term Systolic Cardiac Functions After Kidney Transplant in Children. AB - OBJECTIVES: In this study, our aim was to evaluate the systolic cardiac parameters and related risk factors in children within 6 months after kidney transplant. MATERIALS AND METHODS: We retrospectively evaluated 24 children who received kidney transplants. Clinical and laboratory parameters before and after transplant were recorded. Results were evaluated statistically, with a P value less than .05 considered significant. RESULTS: Before transplant, systolic cardiac functions were within normal limits. After transplant, ejection fraction (63.35% +/- 5.38% vs 66.95% +/- 4.62%; P = .01) was significantly increased and left ventricular mass index (32.63 +/- 17.21 g/m2.7 vs 31.29 +/- 15.65 g/m2.7; P = .78) was not significantly decreased, whereas fractional shortening (52.16% +/- 15.32% vs 59.8% +/- 12.94%; P = .54) did not change. Systolic blood pressure, systolic blood pressure index, diastolic blood pressure, and diastolic blood pressure index values were not statistically different before and after transplant (P > .05). The number of antihypertensive agents was significantly decreased (P = .001). Before and after transplant, cardiac geometry was normal in 15 patients (62.5%) and 17 patients (70.8%). CONCLUSIONS: Our patients, who had stable systolic cardiac function before transplant, showed further improvements in systolic cardiac function even within 6 months after transplant. Therefore, strictly monitored and controlled blood pressure, volume, anemia, and nutrition in children before transplant may play important roles in achieving better cardiac systolic function after kidney transplant. PMID- 26867572 TI - Detection of Babesia annae DNA in lung exudate samples from Red foxes (Vulpes vulpes) in Great Britain. AB - BACKGROUND: This study aimed to determine the prevalence of Babesia species DNA in lung exudate samples collected from red foxes (Vulpes vulpes) from across Great Britain. Babesia are small piroplasmid parasites which are mainly transmitted through the bite of infected ticks of the family Ixodidae. Babesia can cause potentially fatal disease in a wide-range of mammalian species including humans, dogs and cattle, making them of significant economic importance to both the medical and veterinary fields. METHODS: DNA was extracted from lung exudate samples of 316 foxes. A semi-nested PCR was used to initially screen samples, using universal Babesia-Theileria primers which target the 18S rRNA gene. A selection of positive PCR amplicons were purified and sequenced. Subsequently specific primers were designed to detect Babesia annae and used to screen all 316 DNA samples. Randomly selected positive samples were purified and sequenced (GenBank accession KT580786). Clones spanning a 1717 bp region of the 18S rRNA gene were generated from 2 positive samples, the resultant consensus sequence was submitted to GenBank (KT580785). Sequence KT580785 was used in the phylogenetic analysis RESULTS: Babesia annae DNA was detected in the fox samples, in total 46/316 (14.6%) of samples tested positive for the presence of Babesia annae DNA. The central region of England had the highest prevalence at 36.7%, while no positive samples were found from Wales, though only 12 samples were tested from this region. Male foxes were found to have a higher prevalence of Babesia annae DNA than females in all regions of Britain. Phylogenetic and sequence analysis of the GenBank submissions (Accession numbers KT580785 and KT580786) showed 100% identity to Babesia sp.-'Spanish Dog' (AY534602, EU583387 and AF188001). CONCLUSIONS: This is the first time that Babesia annae DNA has been reported in red foxes in Great Britain with positive samples being found across England and Scotland indicating that this parasite is well established within the red fox population of Britain. Phylogenetic analysis demonstrated that though B. annae is closely related to B. microti it is a distinct species. PMID- 26867573 TI - Novel KCNJ10 Gene Variations Compromise Function of Inwardly Rectifying Potassium Channel 4.1. AB - TheKCNJ10gene encoding Kir4.1 contains numerous SNPs whose molecular effects remain unknown. We investigated the functional consequences of uncharacterized SNPs (Q212R, L166Q, and G83V) on homomeric (Kir4.1) and heteromeric (Kir4.1 Kir5.1) channel function. We compared these with previously characterized EAST/SeSAME mutants (G77R and A167V) in kidney-derived tsA201 cells and in glial cell-derived C6 glioma cells. The membrane potentials of tsA201 cells expressing G77R and G83V were significantly depolarized as compared with WTKir4.1, whereas cells expressing Q212R, L166Q, and A167V were less affected. Furthermore, macroscopic currents from cells expressing WTKir4.1 and Q212R channels did not differ, whereas currents from cells expressing L166Q, G83V, G77R, and A167V were reduced. Unexpectedly, L166Q current responses were rescued when co-expressed with Kir5.1. In addition, we observed notable differences in channel activity between C6 glioma cells and tsA201 cells expressing L166Q and A167V, suggesting that there are underlying differences between cell lines in terms of Kir4.1 protein synthesis, stability, or expression at the surface. Finally, we determined spermine (SPM) sensitivity of these uncharacterized SNPs and found that Q212R-containing channels displayed reduced block by 1 MUmSPM. At 100 MUmSPM, the block was equal to or greater than WT, suggesting that the greater driving force of SPM allowed achievement of steady state. In contrast, L166Q Kir5.1 channels achieved a higher block than WT, suggesting a more stable interaction of SPM in the deep pore cavity. Overall, our data suggest that G83V, L166Q, and Q212R residues play a pivotal role in controlling Kir4.1 channel function. PMID- 26867574 TI - Ras-related C3 Botulinum Toxin Substrate (Rac) and Src Family Kinases (SFK) Are Proximal and Essential for Phosphatidylinositol 3-Kinase (PI3K) Activation in Natural Killer (NK) Cell-mediated Direct Cytotoxicity against Cryptococcus neoformans. AB - The activity of Rac in leukocytes is essential for immunity. However, its role in NK cell-mediated anti-microbial signaling remains unclear. In this study, we investigated the role of Rac in NK cell mediated anti-cryptococcal killing. We found thatCryptococcus neoformansindependently activates both Rac and SFK pathways in NK cells, and unlike in tumor killing,Cryptococcusinitiated a novel Rac -> PI3K -> Erk cytotoxicity cascade. Remarkably, Rac was not required for conjugate formation, despite its essential role in NK cytotoxicity againstC. neoformans Taken together, our data show that, unlike observations with tumor cells, NK cells use a novel Rac cytotoxicity pathway in conjunction with SFK, to killC. neoformans. PMID- 26867576 TI - Exploration of the Peptide Recognition of an Amiloride-sensitive FMRFamide Peptide-gated Sodium Channel. AB - FMRFamide (Phe-Met-Arg-Phe-NH2)-activated sodium channel (FaNaC) is an amiloride sensitive sodium channel activated by endogenous tetrapeptide in invertebrates, and belongs to the epithelial sodium channel/degenerin (ENaC/DEG) superfamily. The ENaC/DEG superfamily differs markedly in its means of activation, such as spontaneously opening or gating by mechanical stimuli or tissue acidosis. Recently, it has been observed that a number of ENaC/DEG channels can be activated by small molecules or peptides, indicating that the ligand-gating may be an important feature of this superfamily. The peptide ligand control of the channel gating might be an ancient ligand-gating feature in this superfamily. Therefore, studying the peptide recognition of FaNaC channels would advance our understanding of the ligand-gating properties of this superfamily of ion channels. Here we demonstrate that Tyr-131, Asn-134, Asp-154, and Ile-160, located in the putative upper finger domain ofHelix aspersaFaNaC (HaFaNaC) channels, are key residues for peptide recognition of this ion channel. Two HaFaNaC specific-insertion motifs among the ENaC/DEG superfamily, residing at the putative alpha4-alpha5 linker of the upper thumb domain and the alpha6-alpha7 linker of the upper knuckle domain, are also essential for the peptide recognition of HaFaNaC channels. Chemical modifications and double mutant cycle analysis further indicated that those two specific inserts and key residues in the upper finger domain together participate in peptide recognition of HaFaNaC channels. This ligand recognition site is distinct from that of acid-sensing ion channels (ASICs) by a longer distance between the recognition site and the channel gate, carrying useful information about the ligand gating and the evolution of the trimeric ENaC/DEG superfamily of ion channels. PMID- 26867575 TI - Kinetics of Nitrite Reduction and Peroxynitrite Formation by Ferrous Heme in Human Cystathionine beta-Synthase. AB - Cystathionine beta-synthase (CBS) is a pyridoxal phosphate-dependent enzyme that catalyzes the condensation of homocysteine with serine or with cysteine to form cystathionine and either water or hydrogen sulfide, respectively. Human CBS possesses a noncatalytic heme cofactor with cysteine and histidine as ligands, which in its oxidized state is relatively unreactive. Ferric CBS (Fe(III)-CBS) can be reduced by strong chemical and biochemical reductants to Fe(II)-CBS, which can bind carbon monoxide (CO) or nitric oxide (NO(*)), leading to inactive enzyme. Alternatively, Fe(II)-CBS can be reoxidized by O2to Fe(III)-CBS, forming superoxide radical anion (O2 ()). In this study, we describe the kinetics of nitrite (NO2 (-)) reduction by Fe(II)-CBS to form Fe(II)NO(*)-CBS. The second order rate constant for the reaction of Fe(II)-CBS with nitrite was obtained at low dithionite concentrations. Reoxidation of Fe(II)NO(*)-CBS by O2showed complex kinetic behavior and led to peroxynitrite (ONOO(-)) formation, which was detected using the fluorescent probe, coumarin boronic acid. Thus, in addition to being a potential source of superoxide radical, CBS constitutes a previously unrecognized source of NO(*)and peroxynitrite. PMID- 26867578 TI - Structural and Kinetic Characterization of the 4-Carboxy-2-hydroxymuconate Hydratase from the Gallate and Protocatechuate 4,5-Cleavage Pathways of Pseudomonas putida KT2440. AB - The bacterial catabolism of lignin and its breakdown products is of interest for applications in industrial processing of ligno-biomass. The gallate degradation pathway ofPseudomonas putidaKT2440 requires a 4-carboxy-2-hydroxymuconate (CHM) hydratase (GalB), which has a 12% sequence identity to a previously identified CHM hydratase (LigJ) fromSphingomonassp. SYK-6. The structure of GalB was determined and found to be a member of the PIG-LN-acetylglucosamine deacetylase family; GalB is structurally distinct from the amidohydrolase fold of LigJ. LigJ has the same stereospecificity as GalB, providing an example of convergent evolution for catalytic conversion of a common metabolite in bacterial aromatic degradation pathways. Purified GalB contains a bound Zn(2+)cofactor; however the enzyme is capable of using Fe(2+)and Co(2+)with similar efficiency. The general base aspartate in the PIG-L deacetylases is an alanine in GalB; replacement of the alanine with aspartate decreased the GalB catalytic efficiency for CHM by 9.5 * 10(4)-fold, and the variant enzyme did not have any detectable hydrolase activity. Kinetic analyses and pH dependence studies of the wild type and variant enzymes suggested roles for Glu-48 and His-164 in the catalytic mechanism. A comparison with the PIG-L deacetylases led to a proposed mechanism for GalB wherein Glu-48 positions and activates the metal-ligated water for the hydration reaction and His-164 acts as a catalytic acid. PMID- 26867577 TI - Structural Studies of Lipopolysaccharide-defective Mutants from Brucella melitensis Identify a Core Oligosaccharide Critical in Virulence. AB - The structures of the lipooligosaccharides fromBrucella melitensismutants affected in the WbkD and ManBcoreproteins have been fully characterized using NMR spectroscopy. The results revealed that disruption ofwbkDgives rise to a rough lipopolysaccharide (R-LPS) with a complete core structure (beta-d-Glcp-(1->4) alpha-Kdop-(2->4)[beta-d-GlcpN-(1->6)-beta-d-GlcpN-(1->4)[beta-d-GlcpN-(1->6)] beta-d-GlcpN-(1->3)-alpha-d-Manp-(1->5)]-alpha-Kdop-(2->6)-beta-d-GlcpN3N4P-(1 >6)-alpha-d-GlcpN3N1P), in addition to components lacking one of the terminal beta-d-GlcpN and/or the beta-d-Glcpresidues (48 and 17%, respectively). These structures were identical to those of the R-LPS fromB. melitensisEP, a strain simultaneously expressing both smooth and R-LPS, also studied herein. In contrast, disruption ofmanBcoregives rise to a deep-rough pentasaccharide core (beta-d-Glcp-(1->4)-alpha-Kdop-(2->4)-alpha-Kdop-(2->6)-beta-d-GlcpN3N4P-(1->6) alpha-d-GlcpN3N1P) as the major component (63%), as well as a minor tetrasaccharide component lacking the terminal beta-d-Glcpresidue (37%). These results are in agreement with the predicted functions of the WbkD (glycosyltransferase involved in the biosynthesis of the O-antigen) and ManBcoreproteins (phosphomannomutase involved in the biosynthesis of a mannosyl precursor needed for the biosynthesis of the core and O-antigen). We also report that deletion ofB. melitensis wadCremoves the core oligosaccharide branch not linked to the O-antigen causing an increase in overall negative charge of the remaining LPS inner section. This is in agreement with the mannosyltransferase role predicted for WadC and the lack of GlcpN residues in the defective core oligosaccharide. Despite carrying the O-antigen essential inB. melitensisvirulence, the core deficiency in thewadCmutant structure resulted in a more efficient detection by innate immunity and attenuation, proving the role of the beta-d-GlcpN-(1->6)-beta-d-GlcpN-(1->4)[beta-d-GlcpN-(1->6)]-beta-d-GlcpN-(1 >3)-alpha-d-Manp-(1->5) structure in virulence. PMID- 26867580 TI - Control of the Position of Oxygen Delivery in Soybean Lipoxygenase-1 by Amino Acid Side Chains within a Gas Migration Channel. AB - Understanding gas migration pathways is critical to unraveling structure-function relationships in enzymes that process gaseous substrates such as O2, H2, and N2 This work investigates the role of a defined pathway for O2 in regulating the peroxidation of linoleic acid by soybean lipoxygenase 1. Computational and mutagenesis studies provide strong support for a dominant delivery channel that shuttles molecular oxygen to a specific region of the active site, thereby ensuring the regio- and stereospecificity of product. Analysis of reaction kinetics and product distribution in channel mutants also reveals a plasticity to the gas migration pathway. The findings show that a single site mutation (I553W) limits oxygen accessibility to the active site, greatly increasing the fraction of substrate that reacts with oxygen free in solution. They also show how a neighboring site mutation (L496W) can result in a redirection of oxygen toward an alternate position of the substrate, changing the regio- and stereospecificity of peroxidation. The present data indicate that modest changes in a protein scaffold may modulate the access of small gaseous molecules to enzyme-bound substrates. PMID- 26867581 TI - Association for Medical Education in the Western Pacific Region: Presidential Address 2016. PMID- 26867579 TI - The Platelet Integrin alphaIIbbeta3 Differentially Interacts with Fibrin Versus Fibrinogen. AB - Fibrinogen binding to the integrin alphaIIbbeta3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However,in vivoalphaIIbbeta3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogenversusfibrin to alphaIIbbeta3-mediated platelet functions are unknown. Here, we compared the interaction of alphaIIbbeta3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified alphaIIbbeta3. When alphaIIbbeta3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with alphaIIbbeta3 and a greater binding strength. alphaIIbbeta3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen- and fibrin-alphaIIbbeta3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants alphaD97E or alphaD574E with mutated RGD motifs. Fibrin made from a fibrinogen gamma'/gamma' variant lacking the gammaC alphaIIbbeta3-binding motif was more reactive with alphaIIbbeta3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with alphaIIbbeta3 than fibrinogen. Fibrin is also less sensitive to alphaIIbbeta3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of alphaIIbbeta3 binding activity in the absence of the gammaC-dodecapeptide and the alpha-chain RGD sequences suggests that the alphaIIbbeta3-binding sites in fibrin are not confined to its known gamma-chain and RGD motifs. PMID- 26867583 TI - First Biventricular Jarvik 2000 Implants (Retroauricular Version) Via a Median Sternotomy. AB - OBJECTIVES: Organ shortages and increased numbers of nontransplant older patients have necessitated a search for alternatives to heart transplants. The Jarvik 2000 assist device (Jarvik Heart, Inc., Manhattan, NY, USA), as a small long-term axial flow pump, offers many advantages, such as retroauricular power supply, which minimizes driveline infection risks. When implanted biventricularly, the device may offer support for patients with biventricular heart failure, especially for nontransplant patients as a destination therapy. MATERIALS AND METHODS: We implanted biventricular Jarvik 2000 systems into 3 men (aged, 65.3 +/ 5.0 y; ejection fraction, 24.7% +/- 1.5% for left ventricle and 17.7% +/- 5.0% for right ventricle). These were the first patients worldwide to receive a biventricular Jarvik 2000 device with retroauricular power supply via a median sternotomy and with additional cardiac surgical procedures. RESULTS: No technical problems were noted during biventricular assist device implant. Mean support time on the device was 224 +/- 198 days. All 3 patients showed sufficient cardiac support; 2 patients died from noncardiac complications. Patient 1 died on day 3 as a result of postoperative hepatic failure after preoperative reanimation, and patient 3 died as a result of an ileus and colon perforation after 50 days. Patient 2 died of ventricular fibrillation (after 1.5 y), which occurred 1 year after right ventricular pump shutdown, although significant improvement of right ventricle function was shown (ejection fraction increased by 48%). CONCLUSIONS: Our 3 patients were old, had multiple comorbidities, and needed further cardiac surgery. None of the patients died as a result of technical failure of the device but because of complications accompanying their morbidities. If complication rates can be reduced, a biventricular assist device implant could and should be considered as a potential alternative for nontransplant patients. PMID- 26867582 TI - Relation between phalangeal bone mineral density and radiographic knee osteoarthritis: a cross-sectional study. AB - BACKGROUND: Major reports have suggested that bone mineral density (BMD) is higher in patients with osteoarthritis (OA), while other studies do not agree. Our aim was to examine the cross-sectional association between phalangeal BMD and radiographic knee OA. METHODS: A total of 2855 participants were included in this study. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade >= 2 in at least one leg. BMD scans of the middle phalanges of the second, third and fourth digits of the nondominant hand were performed with a compact radiographic absorptiometry system (Alara MetriScan(r)). A multivariable logistic analysis model was applied to test the relation between phalangeal BMD with radiographic knee OA, the presence of knee osteophytes (OSTs), and knee joint space narrowing (JSN) after adjusting for a number of potential confounding factors. RESULTS: The multivariable-adjusted odds ratios with 95 % confidence intervals [ORs (95 % CI)] of radiographic knee OA across phalangeal BMDs were 1.08 (95 % CI 0.89-1.32) and 0.62 (95 % CI 0.45-0.86), respectively. The P for trend was 0.09. For the female population, the multivariable-adjusted ORs (95 % CI) of radiographic knee OA across phalangeal BMD were 1.01 (95 % CI 0.73-1.37) and 0.58 (95 % CI 0.38 - 0.87), respectively. The P for trend was 0.02. This positive finding, however, did not exist in the male subgroup. There was a significantly lower prevalence of OST in the osteoporosis (OP) group than in the normal group (OR = 0.59, 95 % CI 0.40-0.88; P for trend was 0.01). In contrast, the prevalence of JSN was significantly higher in the osteopenia group (OR = 1.22, 95 % CI 1.00-1.48) and the OP group (OR = 1.35, 95 % CI 1.00-1.84) than in the normal group. The P for trend was 0.02. CONCLUSIONS: This study observed lower odds for the presence of radiographic knee OA and OST in OP patients than in normal subjects. The prevalence of JSN was higher in the osteopenia and OP groups than in normal subjects. PMID- 26867585 TI - Bike Score(r): Associations between urban bikeability and cycling behavior in 24 cities. AB - BACKGROUND: There is growing interest in designing cities that support not only walking, but also cycling. Bike Score(r) is a metric capturing environmental characteristics associated with cycling that is now available for over 160 US and Canadian cities. Our aim was to determine if Bike Score was associated with between and within-city variability in cycling behavior. METHODS: We used linear regression to model associations between Bike Score and journey to work cycling mode share (US: American Community Survey, 2013 or 2012 5-year estimates; Canada: 2011 National Household Survey) for 5664 census tracts in 24 US and Canadian cities. RESULTS: At the city level, the correlation between mean Bike Score and mean journey to work cycling mode share was moderate (r = 0.52). At the census tract level, the correlation was 0.35; a ten-unit increase in Bike Score was associated with a 0.5% (95% CI: 0.5 to 0.6) increase in the proportion of population cycling to work, a meaningful difference given the low modal shares (mean = 1.9%) in many North American cities. Census tracts with the highest Bike Scores (>90 to 100) had mode shares 4.0 higher (beta = 4.0, 95% CI: 2.9 to 5.0) than the lowest Bike Score areas (0-25). City specific analyses indicated between city variability in associations, with regression estimates between Bike Score and mode share ranging from 0.2 to 3.5%. CONCLUSIONS: The Bike Score metric was associated bicycle mode share between and within cities, suggesting its utility for planning bicycle infrastructure. PMID- 26867586 TI - Development of a career coaching model for medical students. AB - PURPOSE: Deciding on a future career path or choosing a career specialty is an important academic decision for medical students. The purpose of this study is to develop a career coaching model for medical students. METHODS: This research was carried out in three steps. The first step was systematic review of previous studies. The second step was a need assessment of medical students. The third step was a career coaching model using the results acquired from the researched literature and the survey. RESULTS: The career coaching stages were defined as three big phases: The career coaching stages were defined as the "crystallization" period (Pre-medical year 1 and 2), "specification" period (medical year 1 and 2), and "implementation" period (medical year 3 and 4). CONCLUSION: The career coaching model for medical students can be used in programming career coaching contents and also in identifying the outcomes of career coaching programs at an institutional level. PMID- 26867584 TI - HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies. AB - BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects >=50 years from six population based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results. PMID- 26867587 TI - Policing of gut microbiota by the adaptive immune system. AB - The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gut microbiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery. PMID- 26867588 TI - Evaluation of a text supported weight maintenance programme 'Lighten Up Plus' following a weight reduction programme: randomised controlled trial. AB - BACKGROUND: Many overweight people find it difficult to maintain weight loss after attending a weight reduction programme. Self-weighing and telephone support are known to be useful methods for self-monitoring for weight loss. We examined the effectiveness of an SMS-text messaging based weight maintenance programme to encourage regular self-weighing in adults who had completed a 12 week commercial weight loss programme. METHODS: Randomised controlled trial of 380 obese or overweight men and women. The intervention group (N = 190) received a single maintenance support phone call and SMS-text based weight maintenance messages over 12 weeks to encourage regular self-weighing after completing their weight loss programme. The primary outcome was change in weight at 9 months follow up. RESULTS: Our sample (N = 380) had a mean age of 47.4 years (SD 13.4), mean baseline weight and BMI of 93.1 kg (16.1) and 34.4 kg/m(2) (5.0) respectively, as well as majority female (87.3%) and White British (80.0%). Using intention to treat analysis both groups regained weight at 9 months follow up; the intervention group regained an average of 1.36 kg while the control group regained 1.81 kg. Adjusting for covariates resulted in a mean difference of 0.45 kg (95% CI -0.78, 1.67) favouring the intervention group at 9 month follow up. CONCLUSIONS: We found no evidence that an SMS based weight maintenance intervention encouraging adults to weigh themselves weekly prevented weight regain at 3 or 9 months after completing a commercial weight loss programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47845106 . PMID- 26867590 TI - Regional variation in the prevalence of overweight/obesity, hypertension and diabetes and their correlates among the adult rural population in India. AB - A community-based, cross-sectional study was carried out in five regions of India by adopting a multistage random sampling procedure. Information was collected from the participants about socio-demographic particulars such as age, sex, occupation, education, etc. Anthropometric measurements such as height, weight and waist and hip circumferences were measured and three measurements of blood pressure were obtained. Fasting blood sugar was assessed using a Glucometer. Data analysis was done using descriptive statistics, chi(2) test for association and logistic regression analysis. A total of 7531 subjects were covered for anthropometry and blood pressure. The overall prevalence of overweight/obesity and abdominal obesity was 29 and 21%, respectively, and was higher in the Southern region (40% each) as compared with other regions. The prevalence of hypertension was 18 and 16% and diabetes was 9.5% each among men and women, respectively. The risk of hypertension and diabetes was significantly higher among adults from the Southern and Western regions, the among elderly, among overweight/obese individuals and those with abdominal obesity. In conclusion, the prevalence of overweight/obesity and hypertension was higher in the Southern region, whereas diabetes was higher in the Southern and Western regions. Factors such as increasing age, male sex, overweight/obesity, and abdominal obesity were important risk factors for hypertension and diabetes. Appropriate health and nutrition education should be given to the community to control these problems. PMID- 26867591 TI - Erratum to: Cloning and Characterization of a Novel NAC Family Gene CarNAC1 from Chickpea (Cicer arietinum L.). PMID- 26867589 TI - Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers. AB - BACKGROUND: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. RESULTS: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR 21 whilst sustained suppression was mediated by miR-499. Moreover the single miR 21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. CONCLUSION: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis. PMID- 26867592 TI - Proteomics analysis of high lipid-producing strain Mucor circinelloides WJ11: an explanation for the mechanism of lipid accumulation at the proteomic level. AB - BACKGROUND: The oleaginous fungus, Mucor circinelloides, is attracting considerable interest as it produces oil rich in gamma-linolenic acid. Nitrogen (N) deficiency is a common strategy to trigger the lipid accumulation in oleaginous microorganisms. Although a simple pathway from N depletion in the medium to lipid accumulation has been elucidated at the enzymatic level, global changes at protein levels upon N depletion have not been investigated. In this study, we have systematically analyzed the changes at the levels of protein expression in M. circinelloides WJ11, a high lipid-producing strain (36 %, lipid/cell dry weight), during lipid accumulation. RESULTS: Proteomic analysis demonstrated that N depletion increased the expression of glutamine synthetase, involved in ammonia assimilation, for the supply of cellular nitrogen but decreased the metabolism of amino acids. Upon N deficiency, many proteins (e.g., fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase) involved in glycolytic pathway were up-regulated while proteins involved in the tricarboxylic acid cycle (e.g., isocitrate dehydrogenase, succinyl-CoA ligase, succinate dehydrogenase, fumarate hydratase) were down-regulated, indicating this activity was retarded thereby leading to a greater flux of carbon into fatty acid biosynthesis. Moreover, glucose-6 phosphate dehydrogenase, transaldolase and transketolase, which participate in the pentose phosphate pathway, were up-regulated, leading to the increased production of NADPH, the reducing power for fatty acid biosynthesis. Furthermore, protein and nucleic acid metabolism were down-regulated and some proteins involved in energy metabolism, signal transduction, molecular chaperone and redox homeostasis were up-regulated upon N depletion, which may be the cellular response to the stress produced by the onset of N deficiency. CONCLUSION: N limitation increased those expressions of the proteins involved in ammonia assimilation but decreased that involved in the biosynthesis of amino acids. Upon N deprivation, the glycolytic pathway was up-regulated, while the activity of the tricarboxylic acid cycle was retarded, thus, leading more carbon flux to fatty acid biosynthesis. Moreover, the pentose phosphate pathway was up-regulated, then this would increase the production of NADPH. Together, coordinated regulation of central carbon metabolism upon N limitation, provides more carbon flux to acetyl CoA and NADPH for fatty acid biosynthesis. PMID- 26867594 TI - Improving fit to work assessments for rail safety workers by exploring work limitations. AB - PURPOSE: We aim to provide evidence for improving fit to work assessments for rail safety workers and raised the question whether adding an assessment of work limitations is useful. Therefore, we assessed differences in the proportions of perceived work limitations and reported health complaints and whether older age or having health complaints are risk factors for having work limitations. METHODS: Job requirements for rail safety workers are 'vigilance and clear judgment', 'good communication abilities', 'sufficient eye sight' and 'task required physical abilities'. We invited 1000 workers to fill in a questionnaire about perceived work limitations and health problems related to their job requirements. Proportions of the two were compared by using the McNemar test. Associations were analyzed by using univariate logistic regression. RESULTS: Among 484 rail safety workers, we found statistically significant differences between the proportions of reported health complaints (2-26 %) and work limitations (10-32 %). No significant associations were found between older age and work limitations, except for workers in the age group 40-50 years regarding physical abilities. This was not found for the age group over 50 years. For each age category, workers reporting health complaints related to 'vigilance and clear judgment' and 'sufficient physical abilities' had a statistically significant increased risk for reporting work limitations as well (ORs 2.4-17.9). CONCLUSIONS: Our results indicate that fit to work assessments should include both health complaints and work limitations. Our results do not substantiate the assumption that workers over 40 years of age are at increased risk for work limitations in general. PMID- 26867593 TI - Effect of tyrosine-rich amelogenin peptide on behavior and differentiation of endothelial cells. AB - BACKGROUND: Enamel matrix derivative (EMD) is an effective biomaterial for periodontal tissue regeneration and might stimulate angiogenesis. Tyrosine-rich amelogenin peptide (TRAP) is present in EMD and is thought to contribute in its biological activity. In the present study, we investigated the effect of chemically synthesized TRAP on proliferation, migration, angiogenic structure formation, and differentiation of human umbilical vein endothelial cells (HUVECs) in vitro. MATERIAL AND METHODS: The effects of TRAP isolated from EMD and chemically synthesized TRAP on proliferation/viability, migration, and angiogenic structure formation were investigated. Expression of angiopoietin-2 (ang-2), von Willebrand factor (vWF), E-selectin, intracellular adhesion molecules 1 (ICAM-1), vascular endothelial growth factor (VEGF) receptors FMS-like tyrosine kinase 1 (FLT-1), and kinase insert domain receptor (KDR) was measured on both messenger RNA (mRNA) and protein levels. RESULTS: The proliferation/viability of HUVECs was inhibited by TRAP at concentration of 100 MUg/ml and slightly stimulated by EMD at similar concentration. Both EMD and TRAP stimulated endothelial cell migration in microchemotaxis chamber. The effect of both TRAP preparations on the migration was significantly higher than that of EMD. All substances stimulated formation of angiogenic structure in vitro. The expression of ICAM-1, E-selectin, FLT-1, KDR, and vWF was significantly increased by both TRAP and EMD at a concentration 50 MUg/ml. The expression of ang-2 was not affected by TRAP but was significantly increased by EMD. CONCLUSION: Our in vitro study shows that TRAP confer the most effects of EMD on the endothelial cells. CLINICAL RELEVANCE: TRAP might be used as a basis for development of new approaches for periodontal regeneration. PMID- 26867595 TI - Road traffic noise, air pollution and myocardial infarction: a prospective cohort study. AB - PURPOSE: Both road traffic noise and air pollution have been linked to cardiovascular disease. However, there are few prospective epidemiological studies available where both road traffic noise and air pollution have been analyzed simultaneously. The aim of this study was to investigate the relation between road traffic noise, air pollution and incident myocardial infarction in both current (1-year average) and medium-term (3-year average) perspective. METHODS: This study was based on a stratified random sample of persons aged 18-80 years who answered a public health survey in Skane, Sweden, in 2000 (n = 13,512). The same individuals received a repeated survey in 2005 and 2010. Diagnoses of myocardial infarction (MI) were obtained from medical records for both inpatient and outpatient specialized care. The endpoint was first MI during 2000-2010. Participants with prior myocardial infarction were excluded at baseline. Yearly average levels of noise (L DEN) and air pollution (NO x ) were estimated using geographic information system for residential address every year until censoring. RESULTS: The mean exposure levels for road traffic noise and air pollution in 2005 were L DEN 51 dB(A) and NO x 11 ug/m(3), respectively. After adjustment for individual confounders (age, sex, body mass index, smoking, education, alcohol consumption, civil status, year, country of birth and physical activity), a 10 dB(A) increase in current noise exposure did not increase the incidence rate ratio (IRR) for MI, 0.99 (95 % CI 0.86-1.14). Neither did a 10-MUg/m(3) increase in current NO x increase the risk of MI, 1.02 (95 % CI 0.86-1.21). The IRR for MI associated with combined exposure to road traffic noise >55 dB(A) and NO x >20 ug/m(3) was 1.21 (95 % CI 0.90-1.64) compared to <55 dB(A) and <20 ug/m(3). CONCLUSIONS: This study did not provide evidence for an increased risk of MI due to exposure to road traffic noise or air pollution at moderate average exposure levels. PMID- 26867596 TI - Inhibition of cancer cell growth by ruthenium complexes. AB - BACKGROUND: Previous studies suggest that certain transition metal complexes, such as cisplatin, are efficacious for treating various cancer types, including ovarian, lung, and breast. METHODS: In order to further evaluate ruthenium (Ru) complexes as potential anti-cancer agents, we synthesized and evaluated Ru-arene complexes. Two complexes with the general formula [Ru (eta (6)-p-cym) (N-N) Cl](+) were tested for their abilities to inhibit cancer cells. RESULTS: The complex with o-phenylenediamine as the N-N ligand (o-PDA) significantly inhibited growth of breast (MDA-MB-231, MCF-7, SKBR-3, and SUM149), lymphoma (Raji), melanoma (Bowes), and osteosarcoma (HT1080); however, the complex with o benzoquinonediimine (o-BQDI) was ineffective except for SUM149. In contrast, o PDA failed to inhibit growth of human breast epithelial cells, MCF-10A. Treatment of MDA-MBA-231 cells with o-PDA resulted in a significant reduction of productions of PDGF-AA, GM-CSF, and VEGF-A proteins at the transcriptional levels. Finally, we demonstrated that o-PDA synergistically inhibited MDA-MB-231 cell growth with cyclophosphamide but not doxorubicin or paclitaxel. CONCLUSION: These results suggest that Ru-arene complexes are promising anti-cancer drugs that inhibit progression and metastasis by blocking multiple processes for breast and other types of cancer. PMID- 26867597 TI - Novel approach for the ammonium removal by simultaneous heterotrophic nitrification and denitrification using a novel bacterial species co-culture. AB - Agricultural activities lead excessive emission of ammonia nitrogen in the environment and can profoundly interfere the equilibrium of the natural ecosystems leading to their contamination. Actually, the biological purification of wastewaters is the most adopted technique thanks to its several advantages such as high performance and low energy consumption. For this reason, two novel strains of Alcaligenes sp. S84S3 and Proteus sp. S19 genus were isolated from an activated sludge and applied in the treatment of ammonium and nitrite in aqueous solution. Under the optimum operating conditions of temperature (30 degrees C), pH (7), carbon substrate (2 g/L of glucose) and duration of incubation time (69 h), the strain Alcaligenes sp. S84S3 could oxidize 65% of the ammonium as high as 272.72 mg-NH4(+)/L. Moreover, during 48 h, the nitrate reduction rate performed by the strain Proteus S19 was about 99 % without production of nitrite intermediate (negligible concentration). Moreover, the coculture of the strains Alcaligenes sp. S84S3 and Proteus sp. S19 could eliminate 65.83% of the ammonium ions without production of toxic forms of nitrogen oxides during a short time of incubation (118 h) at the same operational conditions with providing the aeration in the first treatment phase. The coculture of our isolated strains is assumed to have a good potential for nitrification and denitrification reactions applied in the treatment of wastewater containing ammonium, nitrite and nitrate. As a result, we can consider that the mixed culture is a practical method in the treatment of high-strength ammonium wastewater with reducing of sludge production. PMID- 26867598 TI - Development of leaffolder resistant transgenic rice expressing cry2AX1 gene driven by green tissue-specific rbcS promoter. AB - The insecticidal cry genes of Bacillus thuringiensis (Bt) have been successfully used for development of insect resistant transgenic rice plants. In this study, a novel cry2AX1 gene consisting a sequence of cry2Aa and cry2Ac gene driven by rice rbcS promoter was introduced into a rice cultivar, ASD16. Among 27 putative rice transformants, 20 plants were found to be positive for cry2AX1 gene. The expression of Cry2AX1 protein in transgenic rice plants ranged from 5.95 to 122.40 ng/g of fresh leaf tissue. Stable integration of the transgene was confirmed in putative transformants of rice by Southern blot hybridization analysis. Insect bioassay on T0 transgenic rice plants against rice leaffolder (Cnaphalocrosis medinalis) recorded larval mortality up to 83.33%. Stable inheritance and expression of cry2AX1 gene in T1 progenies was demonstrated using Southern and ELISA. The detached leaf bit bioassay with selected T1 plants showed 83.33-90.00% mortality against C. medinalis. The whole plant bioassay for T1 plants with rice leaffolder showed significant level of resistance even at a lower level of Cry2AX1 expression varying from 131 to 158 ng/g fresh leaf tissue during tillering stage. PMID- 26867599 TI - Bioinformatics analyses of Shigella CRISPR structure and spacer classification. AB - Clustered regularly interspaced short palindromic repeats (CRISPR) are inheritable genetic elements of a variety of archaea and bacteria and indicative of the bacterial ecological adaptation, conferring acquired immunity against invading foreign nucleic acids. Shigella is an important pathogen for anthroponosis. This study aimed to analyze the features of Shigella CRISPR structure and classify the spacers through bioinformatics approach. Among 107 Shigella, 434 CRISPR structure loci were identified with two to seven loci in different strains. CRISPR-Q1, CRISPR-Q4 and CRISPR-Q5 were widely distributed in Shigella strains. Comparison of the first and last repeats of CRISPR1, CRISPR2 and CRISPR3 revealed several base variants and different stem-loop structures. A total of 259 cas genes were found among these 107 Shigella strains. The cas gene deletions were discovered in 88 strains. However, there is one strain that does not contain cas gene. Intact clusters of cas genes were found in 19 strains. From comprehensive analysis of sequence signature and BLAST and CRISPRTarget score, the 708 spacers were classified into three subtypes: Type I, Type II and Type III. Of them, Type I spacer referred to those linked with one gene segment, Type II spacer linked with two or more different gene segments, and Type III spacer undefined. This study examined the diversity of CRISPR/cas system in Shigella strains, demonstrated the main features of CRISPR structure and spacer classification, which provided critical information for elucidation of the mechanisms of spacer formation and exploration of the role the spacers play in the function of the CRISPR/cas system. PMID- 26867600 TI - Effects of saline-alkaline stress on benzo[a]pyrene biotransformation and ligninolytic enzyme expression by Bjerkandera adusta SM46. AB - Benzo[a]pyrene (BaP) accumulates in marine organisms and contaminated coastal areas. The biotreatment of waste water using saline-alkaline-tolerant white rot fungi (WRF) represents a promising method for removing BaP under saline-alkaline conditions based on WRF's ability to produce ligninolytic enzymes. In a pre screening for degradation of polycyclic aromatic hydrocarbons of 82 fungal strains using Remazol brilliant blue R, Bjerkandera adusta SM46 exhibited the highest tolerance to saline-alkaline stress. Moreover, a B. adusta culture grown in BaP-containing liquid medium exhibited resistance to salinities up to 20 g l( 1). These conditions did not inhibit fungal growth or the expression of manganese peroxidase (MnP) or lignin peroxidase (LiP). The degradation rate also became higher as salinity increased to 20 g l(-1). Fungal growth and enzyme expression were inhibited at a salinity of 35 g l(-1). These inhibitory effects directly decreased the degradation rate (>24%). The presence of MnSO4 as an inducer improved the degradation rate and enzyme expression. MnP and LiP activity also increased by seven- and fivefold, respectively. SM46 degraded BaP (38-89% over 30 days) in an acidic environment (pH 4.5) and under saline-alkaline stress conditions (pH 8.2). Investigating the metabolites produced revealed BaP-1,6 dione as the main product, indicating the important role of ligninolytic enzymes in initializing BaP cleavage. The other metabolites detected, naphthalene acetic acid, hydroxybenzoic acid, benzoic acid, and catechol, may have been ring fission products. The wide range of activities observed suggests that B. adusta SM46 is a potential agent for biodegrading BaP under saline conditions. PMID- 26867601 TI - Heterologous expression and characterisation of a laccase from Colletotrichum lagenarium and decolourisation of different synthetic dyes. AB - Laccases have received considerable attention in recent decades because of their ability to oxidise a large spectrum of phenolic and non-phenolic organic substrates and highly recalcitrant environmental pollutants. In this research, a laccase gene from Colletotrichum lagenarium was chemically synthesised using yeast bias codons and expressed in Pichia pastoris. The molecular mass of the recombinant laccase was estimated to be 64.6 kDa by SDS-PAGE, and the enzyme exhibited maximum activity at pH 3.6-4.0 but more stability in buffer with higher pH (>pH 3.6). The optimal reaction temperature of the enzyme was 40 degrees C, beyond which stability significantly decreased. By using 2,2'-azino-bis-(3 ethylbenzothiazoline)-6-sulphonate (ABTS) as a substrate, K m and V max values of 0.34 mM and 7.11 mM min(-1) mg(-1), respectively, were obtained. Using ABTS as a mediator, the laccase could oxidise hydroquinone to p-benzoquinone and decolourise the synthetic dyes malachite green, crystal violet and orange G. These results indicated that the laccase could be used to treat industrial effluents containing artificial dyes. PMID- 26867602 TI - Molecular phylogenetics and anti-Pythium activity of endophytes from rhizomes of wild ginger congener, Zingiber zerumbet Smith. AB - Zingiber zerumbet, a perennial rhizomatous herb exhibits remarkable disease resistance as well as a wide range of pharmacological activities. Towards characterizing the endophytic population of Z. zerumbet rhizomes, experiments were carried out during two different growing seasons viz., early-June of 2013 and late-July of 2014. A total of 34 endophytes were isolated and categorized into 11 morphologically distinct groups. Fungi were observed to predominate bacterial species with colonization frequency values ranging from 12.5 to 50%. Among the 11 endophyte groups isolated, molecular analyses based on ITS/16S rRNA gene sequences identified seven isolate groups as Fusarium solani, two as F. oxysporum and one as the bacterium Rhizobium spp. Phylogenetic tree clustered the ITS sequences from Z. zerumbet endophytes into distinct clades consistent with morphological and sequence analysis. Dual culture assays were carried out to determine antagonistic activity of the isolated endophytes against Pythium myriotylum, an economically significant soil-borne phytopathogen of cultivated ginger. Experiments revealed significant P. myriotylum growth inhibition by F. solani and F. oxysporum isolates with percentage of inhibition (PoI) ranging from 45.17 +/- 0.29 to 62.2 +/- 2.58 with F. oxysporum exhibiting higher PoI values against P. myriotylum. Using ZzEF8 metabolite extract, concentration-dependent P. myriotylum hyphal growth inhibition was observed following radial diffusion assays. These observations were confirmed by scanning electron microscopy analysis wherein exposure to ZzEF8 metabolite extract induced hyphal deformities. Results indicate Z. zerumbet endophytes as promising resources for biologically active compounds and as biocontrol agents for soft rot disease management caused by Pythium spp. PMID- 26867603 TI - [Bleeding during central venous catheterization : Cannot intubate, cannot ventilate due to massive cervical hematoma]. AB - Central venous catheterization is an invasive procedure which can be associated with severe complications. These include in particular unsuccessful arterial puncture and vascular injuries, which in addition to loss of blood can lead to massive soft tissue swelling. A 63-year-old female patient developed massive cervical bleeding during ultrasound-guided internal jugular vein puncture and the rapidly enlarging hematoma led to compromisation of the airway. A cannot intubate, cannot ventilate situation developed and the subsequent hypoxia led to cardiac arrest that was only resolved after emergency surgical tracheotomy during cardiopulmonary resuscitation. PMID- 26867604 TI - [Venous thrombosis and pulmonary embolism : Updated S2 guidelines on diagnostics and therapy]. AB - The updated version of the S2k guidelines on diagnostics and therapy of venous thrombosis and pulmonary embolism have been available since the end of last year. The guidelines deal with the advantages and disadvantages of the currently available investigation and treatment methods, the diagnostic sequence of investigations under various clinical conditions, the invasiveness and duration of therapies and the potential special features of vulnerable patient collectives. This article presents a summary of the most important assertions. PMID- 26867605 TI - Postoperative imaging findings in children with auxiliary partial orthotopic liver transplant (APOLT). AB - Auxiliary partial orthotopic liver transplant (APOLT) is a treatment technique for people who have acute hepatic failure secondary to fulminant hepatic failure and might ultimately recover normal liver function. This surgical procedure is complicated, involving the placement of a liver graft while maintaining viability of the remaining native portion of the liver. This method allows the native liver to recover hepatic function, therefore eliminating the need for long-term immunosuppression, as is typically needed in post-transplant settings. Postoperative imaging in these cases can be challenging given the complex anatomy, specifically the vascular anastomosis. Therefore it is important for radiologists and clinicians to be aware of the anatomy as well as the variable imaging appearances of the liver. We review the imaging findings in children who have undergone auxiliary partial orthotopic liver transplant (APOLT). PMID- 26867607 TI - Childhood asymmetrical labium majus enlargement sonographic and MR imaging appearances. AB - BACKGROUND: Childhood asymmetrical labium majus enlargement (CALME) has been described sparsely in recent surgery, pathology, pediatric and gynecology literature; however, no comprehensive description from a radiology perspective has been developed. OBJECTIVE: The purpose of this case series is to describe the imaging findings of CALME and to review the current understanding of this recently described clinical entity with regard to clinical presentation, pathophysiology, differential diagnosis and treatment options. MATERIALS AND METHODS: This is a retrospective analysis of 3 girls, ages 5-7 years, who presented for imaging evaluation with subsequent pathologically proven CALME. Each child's clinical history, length of symptoms, imaging appearance and pathological findings were reviewed. RESULTS: All three girls presented with unilateral enlargement of the labium majus (two right-side, one left-side) with no history of trauma or other inciting cause. Two girls had painless labial enlargement that was recognized for weeks, and one had similar symptoms for 1 year prior to presentation. One girl was evaluated initially with sonography, and all three children underwent MR imaging. Sonographic evaluation showed asymmetrical labial enlargement without a definable mass. In each girl, the MR imaging findings were characterized by relatively ill-defined T1-weighted hypointense signal, T2-weighted hypo- to isointense signal with interspersed hyperintense septae, and heterogeneous patchy and feathery strands of enhancement on post-contrast imaging. Biopsy from each child showed benign fibrous tissue with intervening mature fibroadipose tissue, vessels and nerves without findings of inflammation or neoplasia. CONCLUSION: The MR imaging appearance of CALME is consistent. Recognition and appreciation of this unique pediatric entity by the radiologist may be essential for appropriate diagnosis and can help to guide therapy. Current preferred treatment approach is conservative. PMID- 26867606 TI - Criteria for radiologic diagnosis of hypochondroplasia in neonates. AB - BACKGROUND: A radiologic diagnosis of hypochondroplasia is hampered by the absence of age-dependent radiologic criteria, particularly in the neonatal period. OBJECTIVE: To establish radiologic criteria and scoring system for identifying neonates with fibroblast growth factor receptor 3 (FGFR3)-associated hypochondroplasia. MATERIALS AND METHODS: This retrospective study included 7 hypochondroplastic neonates and 30 controls. All subjects underwent radiologic examination within 28 days after birth. We evaluated parameters reflecting the presence of (1) short ilia, (2) squared ilia, (3) short greater sciatic notch, (4) horizontal acetabula, (5) short femora, (6) broad femora, (7) metaphyseal flaring, (8) lumbosacral interpedicular distance narrowing and (9) ovoid radiolucency of the proximal femora. RESULTS: Only parameters 1, 3, 4, 5 and 6 were statistically different between the two groups. Parameters 3, 5 and 6 did not overlap between the groups, while parameters 1 and 4 did. Based on these results, we propose a scoring system for hypochondroplasia. Two major criteria (parameters 3 and 6) were assigned scores of 2, whereas 4 minor criteria (parameters 1, 4, 5 and 9) were assigned scores of 1. All neonates with hypochondroplasia in our material scored >=6. CONCLUSION: Our set of diagnostic radiologic criteria might be useful for early identification of hypochondroplastic neonates. PMID- 26867608 TI - Detecting inflammation in the unprepared pediatric colon - how reliable is magnetic resonance enterography? AB - BACKGROUND: Pediatric inflammatory bowel disease frequently affects the colon. MR enterography is used to assess the small bowel but it also depicts the colon. OBJECTIVE: To compare the accuracy of MR enterography and direct visualization at endoscopy in assessing the colon in pediatric inflammatory bowel disease. MATERIALS AND METHODS: We included children with inflammatory bowel disease who had undergone both MR enterography and endoscopy, and we restrospectively assessed the imaging and endoscopic findings. We scored the colonic appearance at MR using a total colon score. We then compared scores for the whole colon and for its individual segments with endoscopy and histology. RESULTS: We included 15 children. An elevated MR colonic segmental score predicted the presence of active inflammation on biopsy with a specificity of 90% (95% confidence interval [CI] 79.5-96.2%) and sensitivity of 60% (CI 40.6-77.3%); this compares reasonably with the predictive values for findings at colonoscopy - specificity 85% (CI 73.4 92.9%) and sensitivity 53.3% (CI 34.3%-71.6%). Accuracy did not change significantly with increasing bowel distension. CONCLUSION: MR-derived scores had comparable accuracy to those derived during visualization at colonoscopy for detecting biopsy-proven inflammation in our patient group. MR enterography might prove useful in guiding biopsy or monitoring treatment response. Collapse of a colonic segment did not impair assessment of inflammation. PMID- 26867609 TI - An index for diagnosing infant hip dysplasia using 3-D ultrasound: the acetabular contact angle. AB - BACKGROUND: Developmental dysplasia of the hip (DDH) is a common condition that is highly treatable in infancy but can lead to the lifelong morbidity of premature osteoarthritis if left untreated. Current diagnostic methods lack reliability, which may be improved by using 3-D ultrasound. OBJECTIVE: Conventional 2-D US assessment of DDH has limitations, including high inter-scan variability. We quantified DDH on 3-D US using the acetabular contact angle (ACA), a property of the 3-D acetabular shape. We assessed ACA reliability and diagnostic utility. MATERIALS AND METHODS: We prospectively collected data from January 2013 to December 2014, including 114 hips in 85 children divided into three clinical diagnostic groups: (1) normal, (2) initially borderline but ultimately normal without treatment and (3) dysplastic requiring treatment. Using custom software, two observers each traced acetabula twice on two 3-D US scans of each hip, enabling automated generation of 3-D surface models and ACA calculation. We computed inter-observer and inter-scan variability of repeatability coefficients and generated receiver operating characteristic (ROC) curves. RESULTS: The 3-D US acetabular contact angle was reproduced 95% of the time within 6 degrees in the same scan and within 9 degrees in different scans of the same hip, vs. 9 degrees and 14 degrees for the 2-D US alpha angle (P < 0.001). Areas under ROC curves for diagnosis of developmental dysplasia of the hip were 0.954 for ACA and 0.927 for alpha angle. CONCLUSION: The 3-D US ACA was significantly more reliable than 2-D US alpha angle, and the 3-D US measurement predicted the presence of DDH with slightly higher accuracy. The ACA therefore shows promising initial diagnostic utility. Our findings call for further study of 3-D US in the diagnosis and longer-term follow-up of infant hip dysplasia. PMID- 26867610 TI - Hydrotropism: Analysis of the Root Response to a Moisture Gradient. AB - Hydrotropism is a genuine response of roots to a moisture gradient to avoid drought. An experimental system for the induction of hydrotropic root response in petri dishes was designed by pioneering groups in the field. This system uses split agar plates containing an osmolyte only in a region of the plate in order to generate a water potential gradient. Arabidopsis seedlings are placed on the MS agar plate so that their root tips are near the junction between plain MS medium and the region supplemented with the osmolyte. This elicits a hydrotropic response in Arabidopsis roots that can be measured as the root curvature angle. PMID- 26867611 TI - Assessing Gravitropic Responses in Arabidopsis. AB - Arabidopsis thaliana was the first higher organism to have its genome sequenced and is now widely regarded as the model dicot. Like all plants, Arabidopsis develops distinct growth patterns in response to different environmental stimuli. This can be seen in the gravitropic response of roots. Methods to investigate this particular tropism are presented here. First, we describe a high-throughput time-lapse photographic analysis of root growth and curvature response to gravistimulation allowing the quantification of gravitropic kinetics and growth rate at high temporal resolution. Second, we present a protocol that allows a quantitative evaluation of gravitropic sensitivity using a homemade 2D clinostat. Together, these approaches allow an initial comparative analysis of the key phenomena associated with root gravitropism between different genotypes and/or accessions. PMID- 26867612 TI - Physiological Analysis of Phototropic Responses in Arabidopsis. AB - Plants utilize light as sole energy source. To maximize light capture they are able to detect the light direction and orient themselves towards the light source. This phototropic response is mediated by the plant blue light photoreceptors phototropin1 and 2 (phot1 and phot2). Although fully differentiated plants also exhibit this response it can be best observed in etiolated seedlings. Differences in light between the illuminated and shaded site of a seedling stem lead to changes in the auxin-distribution, resulting in cell elongation on the shaded site. Since phototropism connects light perception, signaling, and auxin transport, it is of great interest to analyze this response with a fast and simple method.Here we describe a method to analyze the phototropic response of Arabidopsis seedlings. With numerous mutants available, its fast germination and its small size Arabidopsis is well suited for this analysis. Different genotypes can be simultaneously probed in less than a week. PMID- 26867613 TI - Automatic Chloroplast Movement Analysis. AB - In response to low or high intensities of light, the chloroplasts in the mesophyll cells of the leaf are able to increase or decrease their exposure to light by accumulating at the upper and lower sides or along the side walls of the cell respectively. This movement, regulated by the phototropin blue light photoreceptors phot1 and phot2, results in a decreased or increased transmission of light through the leaf. This way the plant is able to optimize harvesting of the incoming light or avoid damage caused by excess light. Here we describe a method that indirectly measures the movement of chloroplasts by taking advantage of the resulting change in leaf transmittance. By using a microplate reader, quantitative measurements of chloroplast accumulation or avoidance can be monitored over time, for multiple samples with relatively little hands-on time. PMID- 26867614 TI - Microscopic and Biochemical Visualization of Auxins in Plant Tissues. AB - Auxins are a particularly notable class of phytohormones in that they regulate plant growth and development at sites of synthesis, and via a regulated polar transport system comprising PIN, ABCB, and AUX/LAX transport proteins. In order to fully understand auxin-regulated physiological processes, it is therefore essential to be able to determine where indole-3-acetic acid and related compounds are being synthesized, where they are transported to, and how much IAA is accumulating in any given tissue. Auxin may be visualized either indirectly, through the use of auxin responsive promoters; directly, through the use of radiolabelled auxin or fluorescent auxin analogs; or biochemically through extraction and mass-spectrometric quantification of auxin and auxin metabolites from target cells or tissues. Here we focus on the use of the DR5::GUS synthetic auxin promoter reporter construct, fluorescent auxin analogs, and confirmatory biochemical (high-pressure liquid chromatography tandem mass-spectrometry) visualization of auxin and auxin metabolites. PMID- 26867615 TI - Immunolocalization of PIN and ABCB Transporters in Plants. AB - PIN auxin efflux carriers and ABCB auxin transporters are important for polar auxin transport, organogenesis and long distance auxin transport. Along with the auxin influx symporter AUX1, they are essential for tropic responses such as gravitropism and phototropism where lateral redistribution of auxin is required for the tropic response to occur. Immunolocalization of plant membrane transporters is an effective technique to determine the transporters' subcellular localization patterns in the tissues of interest, especially when fluorescent protein fusions of the protein of interest are not available. Immunolocalization is also a valuable tool for validation of the localization of fluorescent protein fusions when the fusions are available. Here we describe the procedures to prepare plant tissue samples and fix them for whole mount or embedding and sectioning. We focus on immunolocalizations of PINs and ABCBs in Arabidopsis and maize tissues. In addition, we describe treatments of roots with inhibitors of cellular trafficking: brefeldin A (BFA), a fungal compound that blocks exocytosis; wortmannin, a fungal compound that inhibits phosphatidylinositol 3 kinase and induces fusion of pre-vacuolar compartments and multi-vascular bodies; and oryzalin, a fungal compound that depolymerizes microtubules. Inhibitor treatments are performed prior to fixation and affect the localization patterns of PINs and ABCBs, giving insight into cell type -specific trafficking mechanisms. The procedures described for Arabidopsis and maize can be easily adapted for other herbaceous plants. PMID- 26867616 TI - Analysis of Circadian Leaf Movements. AB - The circadian clock is a molecular timekeeper that controls a wide variety of biological processes. In plants, clock outputs range from the molecular level, with rhythmic gene expression and metabolite content, to physiological processes such as stomatal conductance or leaf movements. Any of these outputs can be used as markers to monitor the state of the circadian clock. In the model plant Arabidopsis thaliana, much of the current knowledge about the clock has been gained from time course experiments profiling expression of endogenous genes or reporter constructs regulated by the circadian clock. Since these methods require labor-intensive sample preparation or transformation, monitoring leaf movements is an interesting alternative, especially in non-model species and for natural variation studies. Technological improvements both in digital photography and image analysis allow cheap and easy monitoring of circadian leaf movements. In this chapter we present a protocol that uses an autonomous point and shoot camera and free software to monitor circadian leaf movements in tomato. PMID- 26867617 TI - Sample Preparation of Arabidopsis thaliana Shoot Apices for Expression Studies of Photoperiod-Induced Genes. AB - Plants produce new organs from a population of pluripotent cells which are located in specific tissues called meristems. One of these meristems, the shoot apical meristem (SAM), gives rise to leaves during the vegetative phase and flowers during the reproductive phase. The transition from vegetative SAM to an inflorescence meristem (IM) is a dramatic developmental switch, which has been particularly well studied in the model species Arabidopsis thaliana. This developmental switch is controlled by multiple environmental signals such as day length (or photoperiod), and it is accompanied by changes in expression of hundreds of genes. A major interest in plant biology is to identify and characterize those genes which are regulated in the stem cells of the SAM in response to the photoperiodic signals. In this sense, techniques such as RNA in situ hybridization (RNA ISH) have been very successfully employed to detect the temporal and spatial expression patterns of genes in the SAM. This method can be specifically optimized for photoperiodic-flowering studies. In this chapter, we describe improved methods to generate plant material and histological samples to be combined with RNA ISH in flowering-related studies. PMID- 26867618 TI - A Luciferase-Based Assay to Test Whether Gene Expression Responses to Environmental Inputs Are Temporally Restricted by the Circadian Clock. AB - Gating is the mechanism by which the influence of an environmental signal on a particular output is temporally restricted by the circadian clock, so that the maximum response of the output to the signal occurs at a specific time. Gated regulation mechanisms have been described for several genes whose expression is strongly induced by light or temperature at certain times but repressed by the circadian clock at others. To reveal a gated pattern of expression in response to light, light pulses are applied in the dark at different times of the 24 h cycle and the transcriptional response of the gene of interest is then monitored with an appropriate technique. Luciferase (LUC) reporters have been the method of choice to study circadian rhythms in the past decades, but this methodology also provides an ideal platform for performing a gating assay. In this chapter, we describe a LUC imaging based protocol designed to test whether the influence of light on the expression of a gene of interest is gated by the circadian clock. PMID- 26867619 TI - Identification of Arabidopsis Transcriptional Regulators by Yeast One-Hybrid Screens Using a Transcription Factor ORFeome. AB - Genetic and molecular approaches revealed that the circadian clock network structure is comprised of several interlocked positive and negative transcriptional feedback loops. The network evolved to sense and integrate inputs from environmental cues to adjust daily rhythms in physiological processes. Compiling evidence indicates that part of this regulation happens at the transcriptional level through subtle adjustments in the expression of core clock genes. Thus, to better understand the network and identify the molecular mechanisms of clock input pathways, it is imperative to determine how core clock genes are regulated. For this purpose we developed reagents for an unbiased approach to identify transcription factors (TFs) interacting with the promoters of core clock genes. At the center of this approach lies the yeast one-hybrid (Y1H) assay in which a pool of proteins fused to the GAL4 transcriptional activation domain are tested for their ability to interact with a selected promoter fragment in yeast cells. Taking advantage of the fact that Arabidopsis TF genes are well annotated, we generated a comprehensive TF clone collection (TF ORFeome) and used it to replace the standard cDNA pool strategy traditionally used in Y1H screens. The use of this TF clone collection substantially accelerates the comprehensive discovery of promoter-specific DNA binding activities among all Arabidopsis TFs. Considering that this strategy can be extended to the study of the promoter interactome of any Arabidopsis gene, we developed a low throughput protocol that can be universally implemented to screen the ~2000 TF clone library. PMID- 26867620 TI - Monitoring Alternative Splicing Changes in Arabidopsis Circadian Clock Genes. AB - Posttranscriptional control makes an important contribution to circadian regulation of gene expression. In higher plants, alternative splicing is particularly prevalent upon abiotic and biotic stress and in the circadian system. Here we describe in detail a high-resolution reverse transcription-PCR based panel (HR RT-PCR) to monitor alternative splicing events. The use of the panel allows the quantification of changes in the proportion of splice isoforms between different samples, e.g., different time points, different tissues, genotypes, ecotypes, or treatments. PMID- 26867621 TI - Assessing the Impact of Photosynthetic Sugars on the Arabidopsis Circadian Clock. AB - Circadian clocks drive 24 h biological rhythms to optimize physiology and development in response to the rotation of the planet. In plants, photosynthesis is modulated by the circadian clock and contributes to daily rhythms in cellular metabolism. In addition to light and temperature, sugar produced from photosynthesis acts as a zeitgeber to contribute to setting of the plant circadian clock. Here, we describe methods to manipulate photosynthetic output and sugar availability in Arabidopsis seedlings. These protocols have been applied to investigate the effects on the Arabidopsis circadian network, but are easily adaptable to other processes in plants. PMID- 26867622 TI - Assessing Protein Stability Under Different Light and Circadian Conditions. AB - Plants use light as an indicator of time and space as well as the major energy source for photosynthesis. Due to the development of specific photoreceptors, plants can perceive a wide range of wavelengths and adjust their development accordingly to their surroundings. In addition to light, the circadian clock allows the anticipation of diurnal and seasonal changes thus providing organisms with the adequate physiological responses to ever changing surroundings, which are reflected in increased fitness and survival rate. Although initially described as a set of interconnected transcriptional loops, it is now accepted that posttranslational modifications are also important for proper clock function. In fact, not only the clock but also light signaling rely on posttranslational modifications, such as phosphorylation and ubiquitination, for proper signal transduction. We have designed a simple and yet reproducible method to determine protein stability and half-life under different light and circadian conditions. Our method only requires standard laboratory equipment, a relatively small amount of starting material and can be applied to young seedlings and mature plants. Besides our application to study light and circadian clock proteins, this protocol can be adapted to any other conditions that regulate protein stability. PMID- 26867624 TI - Basic Techniques to Assess Seed Germination Responses to Abiotic Stress in Arabidopsis thaliana. AB - The model organism Arabidopsis thaliana has been extensively used to unmask the molecular genetic signaling pathways controlling seed germination in plants. In Arabidopsis, the normal seed to seedling developmental transition involves testa rupture soon followed by endosperm rupture, radicle elongation, root hair formation, cotyledon expansion, and greening. Here we detail a number of basic procedures to assess Arabidopsis seed germination in response to different light (red and far-red pulses), temperature (seed thermoinhibition), and water potential (osmotic stress) environmental conditions. We also discuss the role of the endosperm and how its germination-repressive activity can be monitored genetically by means of a seed coat bedding assay. Finally we detail how to evaluate germination responses to changes in gibberellin (GA) and abscisic acid (ABA) levels by manipulating pharmacologically the germination medium. PMID- 26867623 TI - Screening for Abiotic Stress Tolerance in Rice: Salt, Cold, and Drought. AB - Rice (Oryza sativa) is the primary source of food for more than half of the world population. Most rice varieties are severely injured by abiotic stresses, with strong social and economic impact. Understanding rice responses to stress may help breeding for more tolerant varieties. However, papers dealing with stress experiments often describe very different experimental designs, thus making comparisons difficult. The use of identical setups is the only way to generate comparable data. This chapter is organized into three sections, describing the experimental conditions established at the Genomics of Plant Stress (GPlantS) unit of ITQB to assess the response of rice plants to three different abiotic stresses--high salinity, cold stress, and drought. All sections include a detailed description of the materials and methodology, as well as useful notes gathered from the GPlantS team's experience. We use rice seedlings as plants at this stage show high sensitivity to abiotic stresses. For the salt and cold stress assays we use hydroponic cultures, while for the drought assay plants are grown in soil and subjected to water withholding. All setups enable visual score determination and are suitable for sample collection along the imposition of stress. The proposed methodologies are simple and affordable to implement in most labs, allowing the discrimination of several rice genotypes at the molecular and phenotypic level. PMID- 26867625 TI - Assessing Tolerance to Heavy-Metal Stress in Arabidopsis thaliana Seedlings. AB - Heavy-metal soil contamination is one of the major abiotic stress factors that, by negatively affecting plant growth and development, severely limit agricultural productivity worldwide. Plants have evolved various tolerance and detoxification strategies in order to cope with heavy-metal toxicity while ensuring adequate supply of essential micronutrients at the whole-plant as well as cellular levels. Genetic studies in the model plant Arabidopsis thaliana have been instrumental in elucidating such mechanisms. The root assay constitutes a very powerful and simple method to assess heavy-metal stress tolerance in Arabidopsis seedlings. It allows the simultaneous determination of all the standard growth parameters affected by heavy-metal stress (primary root elongation, lateral root development, shoot biomass, and chlorophyll content) in a single experiment. Additionally, this protocol emphasizes the tips and tricks that become particularly useful when quantifying subtle alterations in tolerance to a given heavy-metal stress, when simultaneously pursuing a large number of plant lines, or when testing sensitivity to a wide range of heavy metals for a single line. PMID- 26867626 TI - Assessing Drought Responses Using Thermal Infrared Imaging. AB - Canopy temperature, a surrogate for stomatal conductance, is shown to be a good indicator of plant water status and a potential tool for phenotyping and irrigation scheduling. Measurement of stomatal conductance and leaf temperature has traditionally been done by using porometers or gas exchange analyzers and fine-wire thermocouples attached to the leaves, which are labor intensive and point measurements. The advent of remote or proximal thermal sensing technologies has provided the potential for scaling up to leaves, plants, and canopies. Thermal cameras with a temperature resolution of <0.1 K now allow one to study the temperature variation within and between plants. This chapter discusses some applications of infrared thermography for assessing drought and other abiotic and biotic stress and outlines some of the main factors that need to be considered when applying this to the study of leaf or canopy temperature whether in controlled environments or in the field. PMID- 26867627 TI - Generating Targeted Gene Knockout Lines in Physcomitrella patens to Study Evolution of Stress-Responsive Mechanisms. AB - The moss Physcomitrella patens possesses highly efficient homologous recombination allowing targeted gene manipulations and displays many features of the early land plants including high tolerance to abiotic stresses. It is therefore an invaluable model organism for studies of gene functions and comparative studies of evolution of stress responses in plants. Here, we describe a method for generating targeted gene knockout lines in P. patens using a polyethylene glycol-mediated transformation of protoplasts including basic in vitro growth, propagation, and maintenance techniques. PMID- 26867628 TI - Screening Stress Tolerance Traits in Arabidopsis Cell Cultures. AB - Screening for tolerance traits in plant cell cultures can combine the efficiency of microbial selection and plant genetics. Agrobacterium-mediated transformation can efficiently introduce cDNA library to cell suspension cultures generating population of randomly transformed microcolonies. Transformed cultures can subsequently be screened for tolerance to different stress conditions such as salinity, high osmotic, or oxidative stress conditions. cDNA inserts in tolerant cell lines can be easily identified by PCR amplification and homology search of the determined nucleotide sequences. The described methods have been tested and used to identify regulatory genes controlling salt tolerance in Arabidopsis. As cDNA libraries can be prepared from any plants, natural diversity can be explored by using extremophile plants as gene source. PMID- 26867629 TI - Using Arabidopsis Protoplasts to Study Cellular Responses to Environmental Stress. AB - Arabidopsis mesophyll protoplasts can be readily isolated and transfected in order to transiently express proteins of interest. As freshly isolated mesophyll protoplasts maintain essentially the same physiological characteristics of whole leaves, this cell-based transient expression system can be used to molecularly dissect the responses to various stress conditions. The response of stress responsive promoters to specific stimuli can be accessed via reporter gene assays. Additionally, reporter systems can be easily engineered to address other levels of regulation, such as transcript and/or protein stability. Here we present a detailed protocol for using the Arabidopsis mesophyll protoplast system to study responses to environmental stress, including preparation of reporter and effector constructs, large scale DNA purification, protoplast isolation, transfection, treatment, and quantification of luciferase-based reporter gene activities. PMID- 26867630 TI - Construction of Artificial miRNAs to Prevent Drought Stress in Solanum tuberosum. AB - The use of artificial microRNAs (amiRNAs) is still a relatively new technique in molecular biology with a wide range of applications in life sciences. Here, we describe the silencing of the CBP80/ABH1 gene in Solanum tuberosum with the use of amiRNA. The CBP80/ABH1 protein is part of the Cap Binding Complex (CBC), which is involved in plant responses to drought stress conditions. Transformed plants with a decreased level of CBP80/ABH1 display increased tolerance to water shortage conditions. We describe how to design amiRNA with the Web MicroRNA Designer platform in detail. Additionally, we explain how to perform all steps of a procedure aiming to obtain transgenic potato plants with the use of designed amiRNA, through callus tissue regeneration and Agrobacterium tumefaciens strain LBA4404 as a transgene carrier. PMID- 26867631 TI - Virus-Induced Gene Silencing for Gene Function Studies in Barley. AB - Virus-Induced Gene Silencing (VIGS) creates a natural antiviral defense in plants. However, it has been also a powerful tool for endogenous gene silencing in dicot and monocot plants by exploitation of recombinant viruses, harboring silencing inducing sequences. The Barley Stripe Mosaic Virus (BSMV) based VIGS system is an efficient and rapid RNAi approach that is routinely applied in functional genomics studies of cereals. We present here a protocol for BSMV VIGS application in barley based on mechanical inoculation of the plants with in vitro transcribed recombinant BSMV RNAs as the silencing triggers. PMID- 26867632 TI - Methods for Long-Term Stable Storage of Colletotrichum Species. AB - In this chapter we describe methods for long-term preservation of ascomycete genus Colletotrichum species. Colletotrichum species employ a hemibiotrophic infection strategy and cause clear anthracnose diseases on various host plants including the model plant Arabidopsis thaliana. Their infection proceeds in a highly synchronized manner, which is helpful for the dissection of the fungus plant interactions at the molecular level. Gene engineering methods, including efficient protocols for targeted gene disruption, and whole-genome sequences are available for several Colletotrichum species. Thus, these pathogens provide us with model systems to address the molecular mechanisms underlying hemibiotrophic fungal pathogenicity.We describe how to prepare glycerol stocks or filter paper fungal stocks for long-term preservation of Colletotrichum species. These two methods are easily handled, and provide a stable preservation for at least a few years. PMID- 26867633 TI - Plant Inoculation with the Fungal Leaf Pathogen Colletotrichum higginsianum. AB - After Colletotrichum storage methods in Chapter 23 , we describe here experimental methods for the inoculation of Colletotrichum higginsianum (C.h.) on Arabidopsis leaves. We put a particular focus on the methods for lesion measurements after the drop-inoculation of the leaves and on C.h. biomass measurements in the leaves by RT-qPCR analysis. As an option, we also briefly describe methods for counting C.h. entry ratio. PMID- 26867634 TI - Tracing Plant Defense Responses in Roots upon MAMP/DAMP Treatment. AB - This chapter describes how to apply microbe-associated molecular pattern (MAMP) or damage-associated molecular pattern (DAMP) solutions to Arabidopsis roots to trace defense responses in the root. Plants sense the presence of microbes via the perception of MAMPs or DAMPs by surface-localized pattern recognition receptors. The mechanisms governing plant root immunity are poorly characterized compared with those underlying plant immunity in the leaf, despite the fact that plant roots constantly interact with countless microbes living in soils that carry potential MAMPs and could stimulate the production of plant-derived DAMPs during colonization. To understand how a plant root immune system detects and reacts to the potential sources of a stimulus, we describe a simple method to monitor activation of root immunity upon MAMP/DAMP treatment by measuring relative expression of defense-related genes by RT-qPCR. PMID- 26867635 TI - Analysis of the lmmunity-Related Oxidative Bursts by a Luminol-Based Assay. AB - The rapid production of reactive oxygen species (ROS) in response to biotic and abiotic cues is a conserved hallmark of plant responses. The detection and quantification of ROS generation during immune responses is an excellent readout to analyze signaling triggered by the perception of pathogens. The assay described here is easy to employ and versatile, allowing its use in a multitude of variations. For example, ROS production can be analyzed using different tissues including whole seedlings, roots, leaves, protoplasts, and cultured cells, which can originate from different ecotypes or mutants. Samples can be tested in combination with any ROS-inducing elicitors, such as the FLS2 activating peptide flg22, but also lipids or even abiotic stresses. Furthermore, early (PAMP-triggered) and late (effector-triggered) ROS production induced by virulent and avirulent bacteria, respectively, can also be assayed. PMID- 26867636 TI - Quantitative Analysis of Microbe-Associated Molecular Pattern (MAMP)-Induced Ca(2+) Transients in Plants. AB - Ca(2+) is a secondary messenger involved in early signaling events triggered in response to a plethora of biotic and abiotic stimuli. In plants, environmental cues that induce cytosolic Ca(2+) elevation include touch, reactive oxygen species, cold shock, and salt or osmotic stress. Furthermore, Ca(2+) signaling has been implicated in early stages of plant-microbe interactions of both symbiotic and antagonistic nature. A long-standing hypothesis is that there is information encoded in the Ca(2+) signals (so-called Ca(2+) signatures) to enable plants to differentiate between these stimuli and to trigger the appropriate cellular response. Qualitative and quantitative measurements of Ca(2+) signals are therefore needed to dissect the responses of plants to their environment. Luminescence produced by the Ca(2+) probe aequorin upon Ca(2+) binding is a widely used method for the detection of Ca(2+) transients and other changes in Ca(2+) concentrations in cells or organelles of plant cells. In this chapter, using microbe-associated molecular patterns (MAMPs), such as the bacterial derived flg22 or elf18 peptides as stimuli, a protocol for the quantitative measurements of Ca(2+) fluxes in apoaequorin-expressing seedlings of Arabidopsis thaliana in 96-well format is described. PMID- 26867637 TI - Rapid Assessment of DNA Methylation Changes in Response to Salicylic Acid by Chop qPCR. AB - Methylation of cytosines plays an important role in epigenetic regulation of gene expression. Several methods exist to determine the methylation status of DNA. Here, we describe a rapid and cost-effective method called Chop-qPCR to determine dynamic changes in the DNA methylation patterns, as they occur for instance in response to environmental stresses. PMID- 26867638 TI - Determining Nucleosome Position at Individual Loci After Biotic Stress Using MNase-qPCR. AB - Nucleosome occupancy in promoter and genic regions can severely influence the transcription levels. Few methods have been established to investigate the nucleosome occupancy along the DNA. In this chapter we describe a detailed protocol to analyze the nucleosome occupancy at a specific locus using MNase pPCR. PMID- 26867639 TI - Phosphoprotein Enrichment Combined with Phosphopeptide Enrichment to Identify Putative Phosphoproteins During Defense Response in Arabidopsis thaliana. AB - Phosphoprotein/peptide enrichment is an important technique to elucidate signaling components of defense responses with mass spectrometry. Normally, proteins can be detected easily by shotgun experiments but the low abundance of phosphoproteins hinders their detection. Here, we describe a combination of prefractionation with desalting, phosphoprotein and phosphopeptide enrichment to effectively accumulate phosphorylated proteins from leaf tissue of stressed Arabidopsis plants. PMID- 26867641 TI - Difficulties arising from the variety of testing schemes used for bovine viral diarrhoea virus (BVDV). AB - Globally, the eradication of bovine viral diarrhoea virus (BVDV) is still in its infancy, but eradication has been, or is being, adopted by several countries or regions. Comparisons between countries' schemes allow others to assess best practice, and aggregating published results from eradication schemes provides greater statistical power when analysing data. Aggregating data requires that results derived from different testing schemes be calibrated against one another. The authors aimed to evaluate whether relationships between published BVDV test results could be created and present the outcome of a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. The results are tabulated, providing a summary of papers where there is potential cross-calibration and a summary of the obstacles preventing such data aggregation. Although differences in measuring BVDV present barriers to academic progress, they may also affect progress within individual eradication schemes. The authors examined the time taken to retest following an initial antibody BVDV test in the Scottish eradication scheme. The authors demonstrate that retesting occurred quicker if the initial not negative test was from blood rather than milk samples. Such differences in the response of farmers/veterinarians to tests may be of interest to the design of future schemes. PMID- 26867642 TI - Increased expression of the sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins. AB - Objectives Varicocele is characterized by dilatation and tortuosity of the internal spermatic vein. Sonic hedgehog plays an important role in angiogenesis and vascular remodeling under hypoxic stress. We studied the relationship and distribution of SHH and vascular endothelial growth factor in internal spermatic vein in patients diagnosed with varicocele. Methods Specimens of 1 cm were taken from the internal spermatic vein during left varicocele repair (N = 20). The control samples of ISV were obtained from eight male patients who underwent left inguinal herniorrhaphy. We analyzed the sonic hedgehog and vascular endothelial growth factor expression and distribution by immunoblotting, immunohistochemistry, immunofluorescent staining, and confocal laser scanning microscopy. The data were analyzed using the Student's t test. Results Immunoblotting showed higher expression of sonic hedgehog and vascular endothelial growth factor proteins in varicocele veins than in the control group ( P < 0.05) which located over muscle layer and endothelium was demonstrated by immunohistochemical staining. Both proteins with co-localization in the muscle layer and especially distributed in endothelium of varicocele veins were revealed under confocal microscopy. Conclusions These findings showed the upexpression of sonic hedgehog and vascular endothelial growth factor with co-localization in varicocele veins which imply that the reducing hypoxia or using sonic hedgehog antagonists may be helpful for this vascular disease. PMID- 26867640 TI - Effects of aging on the male reproductive system. AB - The study aims to discuss the effects of aging on the male reproductive system. A systematic review was performed using PubMed from 1980 to 2014. Aging is a natural process comprising of irreversible changes due to a myriad of endogenous and environmental factors at the level of all organs and systems. In modern life, as more couples choose to postpone having a child due to various socioeconomic reasons, research for understanding the effects of aging on the reproductive system has gained an increased importance. Paternal aging also causes genetic and epigenetic changes in spermatozoa, which impair male reproductive functions through their adverse effects on sperm quality and count as, well as, on sexual organs and the hypothalamic-pituitary-gonadal axis. Hormone production, spermatogenesis, and testes undergo changes as a man ages. These small changes lead to decrease in both the quality and quantity of spermatozoa. The offspring of older fathers show high prevalence of genetic abnormalities, childhood cancers, and several neuropsychiatric disorders. In addition, the latest advances in assisted reproductive techniques give older men a chance to have a child even with poor semen parameters. Further studies should investigate the onset of gonadal senesce and its effects on aging men. PMID- 26867643 TI - PD-L1-expressing neutrophils as a novel indicator to assess disease activity and severity of systemic lupus erythematosus. AB - BACKGROUND: It is well-known that increased frequency of neutrophils was found in patients with systemic lupus erythematosus (SLE). However, the immunomodulatory roles and mechanisms of neutrophils in SLE are poorly understood. METHODS: Patients with SLE were recruited from the First Affiliated Hospital of Nanchang University. The medical history, clinical manifestations, physical examination, laboratory measurements, therapeutic regimen and treatment response were recorded. The expression of costimulatory molecules including programmed death 1 (PD-1), programmed death ligand 1 (PD-L1), T-cell immunoglobulin and mucin domain containing protein 3 (Tim-3), CD40, T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT), CD80 and CD86 on neutrophils were determined by flow cytometry. The frequencies of PD-L1 expressing neutrophils in patients with SLE were further analyzed for their correlation with markers of autoimmune response, inflammation, disease activity and severity of SLE. RESULTS: The frequency of PD-L1-expressing neutrophils was significantly elevated in SLE patients compared to the healthy controls (P < 0.0001). The frequency of PD-L1-expressing neutrophils in patients with SLE was increased significantly in subjects with high ANA titre, high anti-nRNP/Sm, high levels of inflammatory markers and high SLE Disease Activity Index (SLEDAI) score. Furthermore, the percentages of PD-L1-expressing neutrophils were significantly decreased in SLE patients that received a 15-day regular treatment with corticosteroids and immunosuppressive drugs (P = 0.0075). CONCLUSION: The frequency of PD-L1-expressing neutrophils is elevates in patients with SLE, correlates with the disease activity and severity of SLE, and may serves as a negative feedback mechanism preventing potential tissue damage caused by excessive autoimmune responses in patients with SLE. PMID- 26867644 TI - Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45. AB - Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma. PMID- 26867645 TI - Antihypertensive treatments for adults with type 2 diabetes. PMID- 26867646 TI - Specific polymorphisms in the vitamin D metabolism pathway are not associated with susceptibility to Chlamydia trachomatis infection in humans. AB - Chlamydia trachomatis is the most common sexually transmitted bacterium worldwide. Its often asymptomatic course of infection increases chances of transmission, and increases risk of late complications. Genetic variations in the host immune system are known to impact the course of infections. Recent studies have shown a positive impact of vitamin D on the regulation of the immune system. This study assesses the impact of eight polymorphisms in five genes [VDR (rs1544410 G > A, rs2228570 C > T), CYP27B1 (rs10877012 G > T), DHCR7 (rs7944926 G > A, rs3829251 G > A), GC (rs3755967) and CYP2R1 (rs10741657 G > A, rs2060793 G > A)] on susceptibility to Chlamydia infections in humans. These polymorphisms could influence protein expression or function, and thus influence the immune system. Samples of women visiting the STD outpatient clinic in South Limburg were genotyped using the Roche Lightcycler 480. In this study, we did not observe statistically significant differences between the genotype distributions of these polymorphisms in women with or without a Chlamydia infection. This suggests that VDR, CYP27B1, DHCR7, GC and CYP2R1 do not affect the susceptibility to Chlamydia infections. However, due to its pleiotropic nature in the immune system a role for the vitamin D pathway may not be excluded from the whole clinical course of Chlamydia infections (e.g. late complications), and further research is required. PMID- 26867647 TI - Genomic prediction of unordered categorical traits: an application to subpopulation assignment in German Warmblood horses. AB - BACKGROUND: Categorical traits without ordinal representation of classes do not qualify for threshold models. Alternatively, the multinomial problem can be assessed by a sequence of independent binary contrasts using schemes such as one vs-all or one-vs-one. Class probabilities can be arrived at by normalization or pair-wise coupling strategies. We assessed the predictive ability of whole-genome regression models and support vector machines for the classification of horses into four German Warmblood breeds. RESULTS: Prediction accuracies of leave-one out cross-validation were high and ranged from 0.75 to 0.97 depending on the binary classifier and breeds incorporated in the training. An analysis of the population structure using eigenvectors of the genomic relationship matrix revealed clustering of individuals beyond the given breed labels. Admixture between two breeds became apparent which had substantial impact on the prediction accuracies between those two breeds and also influenced the contrasts between other breeds. CONCLUSIONS: Genomic prediction of unordered categorical traits was successfully applied to subpopulation assignment of German Warmblood horses. The applied methodology is a straightforward extension of existing binary threshold models for genomic prediction. PMID- 26867648 TI - Transient-state kinetic analysis of complex formation between photoprotein clytin and GFP from jellyfish Clytia gregaria. AB - Luminous organisms use different protein-mediated strategies to modulate light emission color. Here, we report the transient-state kinetic studies of the interaction between photoprotein clytin from Clytia gregaria and its antenna protein, cgreGFP. We propose that cgreGFP forms a transient complex with Ca(2+) bound clytin before the excited singlet state of the coelenteramide product is formed. From the spectral distribution and donor-acceptor separation distance, we infer that clytin reaction intermediates may interact only with the middle side part of cgreGFP. PMID- 26867649 TI - The Bisphenol A analogue Bisphenol S binds to K-Ras4B--implications for 'BPA free' plastics. AB - K-Ras4B is a small GTPase that belongs to the Ras superfamily of guanine nucleotide-binding proteins. GTPases function as molecular switches in cells and are key players in intracellular signalling. Ras has been identified as an oncogene and is mutated in more than 20% of human cancers. Here, we report that Bisphenol S binds into a binding pocket of K-Ras4B previously identified for various low molecular weight compounds. Our results advocate for more comprehensive safety studies on the toxicity of Bisphenol S, as it is frequently used for Bisphenol A-free food containers. PMID- 26867650 TI - TGF-beta triggers HBV cccDNA degradation through AID-dependent deamination. AB - The covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is a viral center molecule for HBV infection and persistence. However, the cellular restriction factors of HBV cccDNA are not well understood. Here, we show that TGF beta can induce nuclear viral cccDNA degradation and hypermutation via activation induced cytidine deaminase (AID) deamination activity in hepatocytes. This suppression by TGF-beta is abrogated when AID or the activity of uracil-DNA glycosylase (UNG) is absent, which indicates that AID deamination and the UNG mediated excision of uracil act in concert to degrade viral cccDNA. Moreover, the HBV core protein promotes the interaction between AID and viral cccDNA. Overall, our results indicate a novel molecular mechanism that allows cytokine TGF-beta to restrict viral nuclear cccDNA in innate immunity, thereby suggesting a novel method for potentially eliminating cccDNA. PMID- 26867652 TI - Radioactive by-products of a self-shielded cyclotron and the liquid target system for F-18 routine production. AB - Routine production of F-18 radionuclide using proton beams accelerated in a cyclotron could potentially generate residual radioisotopes in the cyclotron vicinity which eventually become major safety concerns over radiation exposure to the workers. In this investigation, a typical 11-MeV proton, self-shielded cyclotron has been assessed for its residual radiation sources in the cyclotron's shielding, tank/chamber, cave wall as well as target system. Using a portable gamma ray spectroscopy system, the radiation measurement in the cyclotron environment has been carried out. Experimental results indicate that relatively long-lived radioisotopes such as Mn-54, Zn-65 and Eu-152 are detected in the inner and outer surface of the cyclotron shielding respectively while Mn-54 spectrum is observed around the cyclotron chamber. Weak intensity of Eu-152 radioisotope is again spotted in the inner and outer surface of the cyclotron cave wall. Angular distribution measurement of the Eu-152 shows that the intensity slightly drops with increasing observation angle relative to the proton beam incoming angle. In the target system, gamma rays from Co-56, Mn-52, Co-60, Mn-54, Ag-110 m are identified. TALYS-calculated nuclear cross-section data are used to study the origins of the radioactive by-products. PMID- 26867651 TI - Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report. AB - BACKGROUND: Zoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance. CASE PRESENTATION: A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate. CONCLUSIONS: This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence. PMID- 26867653 TI - Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations. AB - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor alpha) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated. METHODS: We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS). RESULTS: DOG1 was expressed in 66% of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis. CONCLUSIONS: These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification. PMID- 26867654 TI - Serum Antibodies to Glycans in Peripheral Neuropathies. AB - In peripheral neuropathies, such as sensorimotor neuropathies, motor neuron diseases, or the Guillain-Barre syndrome, serum antibodies recognizing saccharide units, portion of oligosaccharides, or oligosaccharide chains, have been found. These antibodies are called anti-glycosphingolipid (GSL) or anti-ganglioside antibodies. However, the information on the aglycone carrying the hydrophilic oligosaccharide remains elusive. The absolute and unique association of GSL to the onset, development and symptomatology of the peripheral neuropathies could be misleading. Here, we report some thoughts on the matter. PMID- 26867655 TI - A Therapeutic Insight of Niacin and Coenzyme Q10 Against Diabetic Encephalopathy in Rats. AB - Diabetes mellitus (DM) is characterized by hyperglycemia due to insulin inactivity or insufficiency with increasing risk of developing specific complications, including retinopathy, nephropathy, neuropathy, and atherosclerosis. The aim of the present study is to evaluate the efficacy of coenzyme Q10 (CoQ10), niacin, as well as their combination in ameliorating brain disorders associated with streptozotocin (STZ)-induced diabetes in rats. Glibenclamide, a reference diabetic drug, and donepezil, an acetylcholine inhibitor drug, were also evaluated. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg body weight (b.wt)). One-month diabetic rats were treated with the selected drugs daily for another two consecutive weeks. The evaluation was done through the estimation of the levels of blood glucose, serum insulin, and oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH); neurotransmitters: acetylcholinesterase (AchE) and dopamine (DA); vasoconstrictor indices: intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1(VCAM-1), and angiotensin II (Ang II); and apoptosis markers: tumor necrosis factor-alpha (TNF-alpha) and caspase-3 as well as the histopathological picture of the cerebellum region of the brain. The results revealed that the combination of niacin and CoQ10 improved most of the measured parameters with variable degrees. In conclusion, niacin and CoQ10 are promising dietary supplements in the management of diabetic encephalopathy. PMID- 26867659 TI - Ruthenium complexes bearing an unsymmetrical pincer ligand with a 2 hydroxypyridylmethylene fragment: active catalysts for transfer hydrogenation of ketones. AB - Five ruthenium(ii) complexes were synthesized, including (HO-C5H3N-CH2-C5H3N C5H4N)Ru(PPh3)Cl2 (3), [(HO-C5H3N-CH2-C5H3N-C5H4N)Ru(PPh3)2Cl][PF6] (4) and [(HO C5H3N-CH2-C5H3N-C5H4N)Ru(PPh3)2OH][PF6] (5) bearing an unsymmetrical pincer NNN ligand with a 2-hydroxypyridylmethylene fragment, and [(CH3O-C5H3N-CH2-C5H3N C5H4N)2Ru][Cl]2 (6) and [(CH3O-C5H3N-CH2-C5H3N-C5H4N)2Ru][PF6]2 (7) containing 2 methoxypyridylmethylene moieties. 4 reacts with H2O at room temperature to give 5 whose crystal structure reveals the existence of intramolecular hydrogen-bonding between its two -OH groups. 3 exhibits high catalytic activity for transfer hydrogenation of ketones. PMID- 26867657 TI - The OPA1 Gene Mutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy. AB - While many patients with hereditary optic neuropathies are caused by mitochondrial DNA (mtDNA) mutations of Leber's hereditary optic neuropathy (LHON), a significant proportion of them does not have mtDNA mutation and is caused by mutations in genes of the nuclear genome. In this study, we investigated whether the OPA1 gene, which is a pathogenic gene for autosomal dominant optic atrophy (ADOA), is frequently mutated in these patients. We sequenced all 29 exons of the OPA1 gene in 105 Han Chinese patients with suspected LHON. mtDNA copy number was quantified in blood samples from patients with and without OPA1 mutation and compared to healthy controls. In silico program-affiliated prediction, evolutionary conservation analysis, and in vitro cellular assays were performed to show the potential pathogenicity of the mutations. We identified nine OPA1 mutations in eight patients; six of them are located in exons and three are located in splicing sites. Mutation c.1172T > G has not been reported before. When we combined our data with 193 reported Han Chinese patients with optic neuropathy and compared to the available data of 4327 East Asians by the Exome Aggregation Consortium (ExAC), we found a significant enrichment of potentially pathogenic OPA1 mutations in Chinese patients. Cellular assays for OPA1 mutants c.869G > A and c.2708_2711del showed abnormalities in OPA1 isoforms, mitochondrial morphology, and cellular reactive oxygen species (ROS) level. Our results indicated that screening OPA1 mutation is needed for clinical diagnosis of patients with suspected optic neuropathy. PMID- 26867658 TI - SAR evolution and discovery of benzenesulfonyl matrinanes as a novel class of potential coxsakievirus inhibitors. AB - MATERIALS & METHODS: Fifty-one novel 12N-substituted matrinic acid derivatives were synthesized and evaluated for their anti-coxsackievirus B3 activities. RESULTS: Structure-activity relationship studies revealed that the 11-side chain could be determinant for the selectivity index by adjusting overall lipophilicity, and 11-butane was the best one for both potency and druggability. The optimized 35d showed the broad-spectrum anti-coxsackieviruse effects, an excellent pharmacokinetics and a good safety profile. More importantly, it displayed a potential effect for the pleconaril-resistant coxsackievirus B3 as well. Its mode of action is targeting on the viral transcription and translation stage, a different mechanism from that of pleconaril. CONCLUSION: Thus, we considered that 35d is a promising anti-enteroviral candidate for the treatment of various diseases infected with coxsackieviruses. PMID- 26867660 TI - Unique piezochromic fluorescence behavior of organic crystal of carbazole substituted CNDSB. AB - CzCNDSB with a highly twisted conformation in the solid state is constructed. Single crystal measurements prove that it possesses an inside pore with a diameter of 8 A and further forms a long-range orderly arrayed channel. CzCNDSB can sense external pressure from 1.0 atm to 9.21 GPa, accompanied by color changes from green to red with excellent reversibility and reproducibility. PMID- 26867656 TI - Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF kappaB Signaling Pathway Following Subarachnoid Hemorrhage in Mice. AB - Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-kappaB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-kappaB (Ac-NF-kappaB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-kappaB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF kappaB signaling pathway. PMID- 26867661 TI - Effectiveness of malaria control interventions in Madagascar: a nationwide case control survey. AB - BACKGROUND: Madagascar, as other malaria endemic countries, depends mainly on international funding for the implementation of malaria control interventions (MCI). As these funds no longer increase, policy makers need to know whether these MCI actually provide the expected protection. This study aimed at measuring the effectiveness of MCI deployed in all transmission patterns of Madagascar in 2012-2013 against the occurrence of clinical malaria cases. METHODS: From September 2012 to August 2013, patients consulting for non-complicated malaria in 31 sentinel health centres (SHC) were asked to answer a short questionnaire about long-lasting insecticidal nets (LLIN) use, indoor residual spraying (IRS) in the household and intermittent preventive treatment of pregnant women (IPTp) intake. Controls were healthy all-ages individuals sampled from a concurrent cross sectional survey conducted in areas surrounding the SHC. Cases and controls were retained in the database if they were resident of the same communes. The association between Plasmodium infection and exposure to MCI was calculated by multivariate multilevel models, and the protective effectiveness (PE) of an intervention was defined as 1 minus the odds ratio of this association. RESULTS: Data about 841 cases (out of 6760 cases observed in SHC) and 8284 controls was collected. The regular use of LLIN provided a significant 51 % PE (95 % CI [16 71]) in multivariate analysis, excluding in one transmission pattern where PE was -11 % (95 % CI [-251 to 65]) in univariate analysis. The PE of IRS was 51 % (95 % CI [31-65]), and the PE of exposure to both regular use of LLIN and IRS was 72 % (95 % CI [28-89]) in multivariate analyses. Vector control interventions avoided yearly over 100,000 clinical cases of malaria in Madagascar. The maternal PE of IPTp was 73 %. CONCLUSIONS: In Madagascar, LLIN and IRS had good PE against clinical malaria. These results may apply to other countries with similar transmission profiles, but such case-control surveys could be recommended to identify local failures in the effectiveness of MCI. PMID- 26867662 TI - Vitamin D deficiency and its role in neurological conditions: A review. AB - This review exposes recent advances on the role of vitamin D, cholecalciferol, a secosteroid, in the central nervous system. In humans, vitamin D arises from cutaneous transformation of 7-dehydrocholesterol under the effect of UVB exposure or from food intake. Vitamin D has an immunomodulatory role through its anti inflammatory and anti-autoimmune actions. In the nervous system, vitamin D is involved in the regulation of calcium-mediated neuronal excitotoxicity, in the reduction of oxidative stress, and in the induction of synaptic structural proteins, neurotrophic factors and deficient neurotransmitters. Reduced exposure to sunlight and low food intake can lead to vitamin D deficiency. Increasing evidence highlights the impact of vitamin D deficiency as a favoring factor in various central or peripheral neurological diseases, especially multiple sclerosis and several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. Recently, several clinical trials on vitamin D supplementation stressed the role of vitamin D as a protective and/or prognostic factor in the onset and progress of such neurological conditions. PMID- 26867663 TI - [Cerebral vasculitis: A rare complication of pneumococcal meningitis]. PMID- 26867664 TI - Rapid specimen preparation to improve the throughput of electron microscopic volume imaging for three-dimensional analyses of subcellular ultrastructures with serial block-face scanning electron microscopy. AB - Serial block-face imaging using scanning electron microscopy enables rapid observations of three-dimensional ultrastructures in a large volume of biological specimens. However, such imaging usually requires days for sample preparation to reduce charging and increase image contrast. In this study, we report a rapid procedure to acquire serial electron microscopic images within 1 day for three dimensional analyses of subcellular ultrastructures. This procedure is based on serial block-face with two major modifications, including a new sample treatment device and direct polymerization on the rivets, to reduce the time and workload needed. The modified procedure without uranyl acetate can produce tens of embedded samples observable under serial block-face scanning electron microscopy within 1 day. The serial images obtained are similar to the block-face images acquired by common procedures, and are applicable to three-dimensional reconstructions at a subcellular resolution. Using this approach, regional immune deposits and the double contour or heterogeneous thinning of basement membranes were observed in the glomerular capillary loops of an autoimmune nephropathy model. These modifications provide options to improve the throughput of three dimensional electron microscopic examinations, and will ultimately be beneficial for the wider application of volume imaging in life science and clinical medicine. PMID- 26867666 TI - Psychiatric governance, volkisch corporatism, and the German Research Institute of Psychiatry in Munich (1912-26). Part 2. AB - This is the second of two articles exploring in depth some of the early organizational strategies that were marshalled in efforts to found and develop the German Research Institute of Psychiatry (Deutsche Forschungsanstalt fur Psychiatrie). The first article analysed the strategies of psychiatric governance - best understood as a form of volkisch corporatism - that mobilized a group of stakeholders in the service of higher bio-political and hygienic ends. This second article examines how post-war imperatives and biopolitical agendas shaped the institute's organization and research. It also explores the financial challenges the institute faced amidst the collapse of the German financial system in the early Weimar Republic, including efforts to recruit financial support from the Rockefeller Foundation and other philanthropists in the USA. PMID- 26867665 TI - Influence of Ku86 and XRCC4 expression in uterine cervical cancer on the response to preoperative radiotherapy. AB - DNA double-strand breaks (DSB) are severe damages induced by ionizing radiation. Non-homologous end joining (NHEJ) is a major mechanism for repairing DSB. Immunohistochemical analysis of proteins involved in NHEJ, such as Ku86 and XRCC4 (X-ray repair cross-complementing protein 4) may be useful for predicting tumor radiosensitivity. We examined the relationship between expression of DSB-related proteins in biopsy specimens of uterine cervical cancer and the pathological effect of 40 Gy of preoperative radiotherapy. 119 patients with uterine cervical cancer were treated between 2000 and 2011. Pathological effects of preoperative radiotherapy were classified by examining hysterectomy specimens. Patients with complete response (pCR) had a significantly better overall 5-year survival rate than those without pCR (96.3 vs. 76.9 %, P = 0.02). The pCR rate was significantly higher in patients with low Ku86 and XRCC4 expression than in other patients (47.4 vs. 21.3 %, P = 0.04). Logistic regression analysis also demonstrated that low Ku86 and XRCC4 expression was a significant predictor of pCR (P = 0.03). Patients with high Ku86 and XRCC4 expression had a significantly lower 5-year metastasis-free rate than others (79.3 vs. 93.5 %, P = 0.02). Proteins involved with NHEJ might have an influence on results of radiotherapy for uterine cervical cancer. PMID- 26867667 TI - Removal versus retention of asymptomatic third molars in mandibular angle fractures: a randomized controlled trial. AB - The treatment dilemma provided by asymptomatic third molars in mandibular angle fractures remains controversial. This prospective randomized controlled trial was undertaken to determine whether there is an advantage to extraction or retention of the third molar whilst repairing a mandibular angle fracture. Sixty-four patients were allocated randomly to the two treatment groups. All underwent open reduction and internal fixation (ORIF) with standard postoperative care. The primary outcome measure was uncomplicated fracture healing. Secondary measures were surgical duration, malocclusion, wound healing, nerve injury, and return to theatre. All patients had uncomplicated fracture healing. The incidence of nerve injury was 16% for the retention group compared with 39% for the removal group (P=0.038). The average operating time for ORIF and third molar retention cases was 58.5min and for ORIF and third molar removal cases was 66.3min (P=0.26). There was no statistically significant difference between groups for wound healing, occlusion outcomes, or return to theatre. Given the additional risk of nerve injury and the additional operating time required for removal of a third molar, in the absence of an absolute indicator for removal of the third molar, it appears justifiable to advise retaining the tooth in the line of a mandibular angle fracture. PMID- 26867668 TI - Mandibular distraction osteogenesis for the management of upper airway obstruction in children with micrognathia: a systematic review. AB - Mandibular distraction osteogenesis (MDO) is increasingly used for neonates and infants with upper airway obstruction secondary to micrognathia. This systematic review was conducted to determine the effectiveness of MDO in the treatment of airway obstruction. The databases searched included PubMed, Embase, Scopus, and grey literature sources. The inclusion criteria were applied to identify studies in children with clinical evidence of micrognathia/Pierre Robin sequence (PRS) who had failed conservative treatments, including both syndromic and non syndromic patients. Overall 66 studies were included in this review. Primary MDO for the relief of upper airway obstruction was found to be successful at preventing tracheostomy in 95% of cases. Syndromic patients were found to have a four times greater odds of failure compared to those with isolated PRS. The most common causes of failure were previously undiagnosed lower airway obstruction, central apnoea, undiagnosed neurological abnormalities, and the presence of additional cardiovascular co-morbidities. MDO was less effective (81% success rate) at facilitating decannulation of tracheostomy-dependent children (P<0.0001). Failure in these patients was most commonly due to severe preoperative gastro-oesophageal reflux disease, swallowing dysfunction, and tracheostomy-related complications. The failure rate was higher when MDO was performed at an age of >=24 months. More studies are needed to evaluate the long term implications of MDO on facial development and long-term complications. PMID- 26867670 TI - Clinical impact of low-burden BCR-ABL1 mutations detectable by amplicon deep sequencing in Philadelphia-positive acute lymphoblastic leukemia patients. PMID- 26867669 TI - Clonal B cells in Waldenstrom's macroglobulinemia exhibit functional features of chronic active B-cell receptor signaling. AB - Waldenstrom's macroglobulinemia (WM) is a B-cell non-Hodgkin's lymphoma (B-NHL) characterized by immunoglobulin M (IgM) monoclonal gammopathy and the medullary expansion of clonal lymphoplasmacytic cells. Neoplastic transformation has been partially attributed to hyperactive MYD88 signaling, secondary to the MYD88 L265P mutation, occurring in the majority of WM patients. Nevertheless, the presence of chronic active B-cell receptor (BCR) signaling, a feature of multiple IgM+ B-NHL, remains a subject of speculation in WM. Here, we interrogated the BCR signaling capacity of primary WM cells by utilizing multiparametric phosphoflow cytometry and found heightened basal phosphorylation of BCR-related signaling proteins, and augmented phosphoresponses on surface IgM (sIgM) crosslinking, compared with normal B cells. In support of those findings we observed high sIgM expression and loss of phosphatase activity in WM cells, which could both lead to signaling potentiation in clonal cells. Finally, led by the high-signaling heterogeneity among WM samples, we generated patient-specific phosphosignatures, which subclassified patients into a 'high' and a 'healthy-like' signaling group, with the second corresponding to patients with a more indolent clinical phenotype. These findings support the presence of chronic active BCR signaling in WM while providing a link between differential BCR signaling utilization and distinct clinical WM subgroups. PMID- 26867671 TI - Donor cell-derived hematological malignancy: a survey by the Japan Society for Hematopoietic Cell Transplantation. PMID- 26867672 TI - Evaluation of bone surrogates for indirect and direct ballistic fractures. AB - The mechanism of injury for fractures to long bones has been studied for both direct ballistic loading as well as indirect. However, the majority of these studies have been conducted on both post-mortem human subjects (PMHS) and animal surrogates which have constraints in terms of storage, preparation and testing. The identification of a validated bone surrogate for use in forensic, medical and engineering testing would provide the ability to investigate ballistic loading without these constraints. Two specific bone surrogates, Sawbones and Synbone, were evaluated in comparison to PMHS for both direct and indirect ballistic loading. For the direct loading, the mean velocity to produce fracture was 121 +/ 19 m/s for the PMHS, which was statistically different from the Sawbones (140 +/ 7 m/s) and Synbone (146 +/- 3 m/s). The average distance to fracture in the indirect loading was .70 cm for the PMHS. The Synbone had a statistically similar average distance to fracture (.61 cm, p=0.54) however the Sawbones average distance to fracture was statistically different (.41 cm, p<0.05). Fractures patterns were found to be comparable to the PMHS for tests conducted with Synbones, however the input parameters were slightly varied to produce similar results. The fractures patterns with the Sawbones were not found to be as comparable to the PMHS. An ideal bone surrogate for ballistic testing was not identified and future work is warranted. PMID- 26867673 TI - Spontaneous and strong multi-layer graphene n-doping on soda-lime glass and its application in graphene-semiconductor junctions. AB - Scalable and low-cost doping of graphene could improve technologies in a wide range of fields such as microelectronics, optoelectronics, and energy storage. While achieving strong p-doping is relatively straightforward, non-electrostatic approaches to n-dope graphene, such as chemical doping, have yielded electron densities of 9.5 * 10(12) e/cm(2) or below. Furthermore, chemical doping is susceptible to degradation and can adversely affect intrinsic graphene's properties. Here we demonstrate strong (1.33 * 10(13) e/cm(2)), robust, and spontaneous graphene n-doping on a soda-lime-glass substrate via surface-transfer doping from Na without any external chemical, high-temperature, or vacuum processes. Remarkably, the n-doping reaches 2.11 * 10(13) e/cm(2) when graphene is transferred onto a p-type copper indium gallium diselenide (CIGS) semiconductor that itself has been deposited onto soda-lime-glass, via surface transfer doping from Na atoms that diffuse to the CIGS surface. Using this effect, we demonstrate an n-graphene/p-semiconductor Schottky junction with ideality factor of 1.21 and strong photo-response. The ability to achieve strong and persistent graphene n-doping on low-cost, industry-standard materials paves the way toward an entirely new class of graphene-based devices such as photodetectors, photovoltaics, sensors, batteries, and supercapacitors. PMID- 26867674 TI - Further patient information; Takotsubo cardiomyopathy related to autonomic nervous system. PMID- 26867676 TI - Exposure of CCRF-CEM cells to acridone derivative 8a triggers tumor death via multiple mechanisms. AB - A newly synthesized acridone derivative 8a shows potent antitumor activity against CCRF-CEM leukemia cells. Herein, the first proteomic study of 8a effects in CCRF-CEM cells was performed by 2D nano-LC-ESI-MS/MS to better understand the mechanisms of action of 8a. Data analyses based on PLGS, STRING, Cytoscape, and database for annotation, visualization, and integrated discovery identified 55 proteins that were differentially expressed in response to 8a exposure. Multiple cellular pathways were affected, including chromatin organization, energy metabolism, DNA repair, oxidative-stress, and apoptosis. The changes in protein expression were further verified for PKM2. Moreover, 8a lowered down the expression of HEX and PFK-1. Lactate production was decreased in 8a-treated cells, indicating suppression of glycolysis. The elevated XRCC6 and decreased histone expression levels suggested increased DNA damage in 8a-treated cells, which was confirmed by the increased gamma-H2AX foci. Molecular docking of 8a with DNA demonstrated direct interactions of 8a with DNA through three hydrogen bonds and four pi-pi interactions, potentially explaining the mode of action that 8a damaged to DNA. The differential protein profiling and dysfunction of metabolic pathways induced by 8a provide novel insights into the potential action mechanisms of 8a. PMID- 26867675 TI - TGF-beta1 regulates human brain pericyte inflammatory processes involved in neurovasculature function. AB - BACKGROUND: Transforming growth factor beta 1 (TGFbeta1) is strongly induced following brain injury and polarises microglia to an anti-inflammatory phenotype. Augmentation of TGFbeta1 responses may therefore be beneficial in preventing inflammation in neurological disorders including stroke and neurodegenerative diseases. However, several other cell types display immunogenic potential and identifying the effect of TGFbeta1 on these cells is required to more fully understand its effects on brain inflammation. Pericytes are multifunctional cells which ensheath the brain vasculature and have garnered recent attention with respect to their immunomodulatory potential. Here, we sought to investigate the inflammatory phenotype adopted by TGFbeta1-stimulated human brain pericytes. METHODS: Microarray analysis was performed to examine transcriptome-wide changes in TGFbeta1-stimulated pericytes, and results were validated by qRT-PCR and cytometric bead arrays. Flow cytometry, immunocytochemistry and LDH/Alamar Blue(r) viability assays were utilised to examine phagocytic capacity of human brain pericytes, transcription factor modulation and pericyte health. RESULTS: TGFbeta1 treatment of primary human brain pericytes induced the expression of several inflammatory-related genes (NOX4, COX2, IL6 and MMP2) and attenuated others (IL8, CX3CL1, MCP1 and VCAM1). A synergistic induction of IL-6 was seen with IL-1beta/TGFbeta1 treatment whilst TGFbeta1 attenuated the IL-1beta-induced expression of CX3CL1, MCP-1 and sVCAM-1. TGFbeta1 was found to signal through SMAD2/3 transcription factors but did not modify nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) translocation. Furthermore, TGFbeta1 attenuated the phagocytic ability of pericytes, possibly through downregulation of the scavenger receptors CD36, CD47 and CD68. Whilst TGFbeta did decrease pericyte number, this was due to a reduction in proliferation, not apoptotic death or compromised cell viability. CONCLUSIONS: TGFbeta1 attenuated pericyte expression of key chemokines and adhesion molecules involved in CNS leukocyte trafficking and the modulation of microglial function, as well as reduced the phagocytic ability of pericytes. However, TGFbeta1 also enhanced the expression of classical pro-inflammatory cytokines and enzymes which can disrupt BBB functioning, suggesting that pericytes adopt a phenotype which is neither solely pro- nor anti-inflammatory. Whilst the effects of pericyte modulation by TGFbeta1 in vivo are difficult to infer, the reduction in pericyte proliferation together with the elevated IL-6, MMP-2 and NOX4 and reduced phagocytosis suggests a detrimental action of TGFbeta1 on neurovasculature. PMID- 26867679 TI - Effect of preceding crop on Fusarium species and mycotoxin contamination of wheat grains. AB - BACKGROUND: The Fusarium graminearum species complex infects several cereals and causes the reduction of grain yield and quality. Many factors influence the extent of Fusarium infection and mycotoxin levels. Such factors include crop rotation. In the present study, we explored the effect of rice or maize as former crops on mycotoxin accumulation in wheat grains. RESULTS: More than 97% of samples were contaminated with deoxynivalenol (DON). DON concentrations in wheat grains from rice and maize rotation fields were 884.37 and 235.78 ug kg(-1) . Zearalenone (ZEN) was detected in 45% of samples which were mainly collected from maize-wheat rotation systems. Fusarium strains were isolated and more F. graminearum sensu stricto (s. str.) isolates were cultured from wheat samples obtained from maize rotation fields. DON levels produced by Fusarium isolates from rice rotation fields were higher than those of samples from maize rotation fields. CONCLUSIONS: Rice-wheat rotation favours DON accumulation, while more ZEN contamination may occur in maize-wheat rotation models. Appropriate crop rotation may help to reduce toxin levels in wheat grains. (c) 2016 Society of Chemical Industry. PMID- 26867677 TI - Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation. AB - BACKGROUND: The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes. METHODS: Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation (FC) or constipation-predominant irritable bowel syndrome (IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms (PAC-SYM), and the treatment satisfaction questionnaire for medication (TSQM-2). Wave 2 only included a global rating of change (GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC-SYM item 3. KEY RESULTS: The average age was 50.1 years (SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% (n = 1970). Bloating was associated with SF-12 Physical Composite Score (p < 0.01), SF 12 Mental Composite Score (p < 0.01), GRC (p < 0.01), Satisfaction with treatment effectiveness (p < 0.01), convenience of administration (p < 0.01), and side effects (p < 0.01) after adjustment for possible confounders. CONCLUSIONS & INFERENCES: Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient-reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain. PMID- 26867678 TI - SIRT7-dependent deacetylation of the U3-55k protein controls pre-rRNA processing. AB - SIRT7 is an NAD(+)-dependent protein deacetylase with important roles in ribosome biogenesis and cell proliferation. Previous studies have established that SIRT7 is associated with RNA polymerase I, interacts with pre-ribosomal RNA (rRNA) and promotes rRNA synthesis. Here we show that SIRT7 is also associated with small nucleolar RNP (snoRNPs) that are involved in pre-rRNA processing and rRNA maturation. Knockdown of SIRT7 impairs U3 snoRNA dependent early cleavage steps that are necessary for generation of 18S rRNA. Mechanistically, SIRT7 deacetylates U3-55k, a core component of the U3 snoRNP complex, and reversible acetylation of U3-55k modulates the association of U3-55k with U3 snoRNA. Deacetylation by SIRT7 enhances U3-55k binding to U3 snoRNA, which is a prerequisite for pre-rRNA processing. Under stress conditions, SIRT7 is released from nucleoli, leading to hyperacetylation of U3-55k and attenuation of pre-rRNA processing. The results reveal a multifaceted role of SIRT7 in ribosome biogenesis, regulating both transcription and processing of rRNA. PMID- 26867680 TI - The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers. AB - Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo. PMID- 26867681 TI - Neonatal phthalate ester exposure induced placental MTs, FATP1 and HFABP mRNA expression in two districts of southeast China. AB - Plastic production releases phthalate esters (PAEs), which can alter the expression of metallothioneins (MTs), fatty acid transport protein 1 (FATP1) and heart fatty acid binding protein (HFABP). A total of 187 mother-infant pairs were recruited, 127 from Chenghai (high exposed group) and 60 from Haojiang (low exposed group), to investigate the association between neonatal PAE exposure and mRNA expression of placental MTs, FATP1 and HFABP. Umbilical cord blood and placenta samples were collected for measuring five PAE concentrations and detecting mRNA levels of MTs, FATP1 and HFABP. Butylbenzyl phthalate (BBP), di(2 ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP) were significantly higher in the high exposed group compared to the low exposed group. FATP1 and HFABP mRNA in the high exposed group were higher than that in the low exposed group while MT-1A was contrary. Both dimethyl phthalate (DMP) and DEHP were correlated with higher MT and MT-2A expression, while diethyl phthalate (DEP) was also positively correlated with MT-1A and FATP1 expression in female infants. DEHP exposure was negatively correlated with birth weight and gestational age in male infants. These results show that neonatal PAE exposure alters the mRNA expression of placental MTs and FATP1, which are related to fetal growth and development. PMID- 26867684 TI - The importance of using the entire face to assess facial profile attractiveness. AB - INTRODUCTION: The aim of this study was to evaluate the importance of using the entire face to assess facial profile attractiveness. The secondary objective was to assess the facial profile preferences of orthodontists, dentists and laypeople. METHODS: Two original cephalometric radiographs of two subjects (one man and one woman meeting the normality criteria) and 16 modified samples of these radiographs were used. The 18 radiographs were then converted into silhouettes and printed twice: the entire profile (A) and the lower third alone (B). The silhouettes were randomly distributed into two binders A and B. A survey was conducted using three panels of evaluators: orthodontists, dentists and laypeople. The esthetic appreciation was quantified according to the Visual Analogue Scale (VAS). RESULTS: Pearson's correlation coefficient was calculated to compare the scores of the entire profile with the scores of the lower third alone. The results showed that the orthodontists panel presented a much better correlation between A and B compared to dentists and especially to laypeople. A comparison of profile scores with the correlation coefficients shows that the profiles with the highest scores present the lowest correlations. The three panels of evaluators preferred the orthogonal profiles or profiles with upper lip protrusion over profiles with lower lip protrusion. CONCLUSION: For profiles with values close to the norm, the lower face alone does not reveal the attractiveness of the entire facial profile. Hence, the importance of using the entire facial profile to assess the beauty of the face. PMID- 26867682 TI - CHK1 expression in Gastric Cancer is modulated by p53 and RB1/E2F1: implications in chemo/radiotherapy response. AB - Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient's samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1's expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgery. PMID- 26867685 TI - Influence of nutrients on oxidation of low level methane by mixed methanotrophic consortia. AB - Low-level methane emissions from coal mine ventilation air (CMV-CH4; i.e., 1 % CH4) can significantly contribute to global climate change, and therefore, treatment is important to reduce impacts. To investigate CMV-CH4 abatement potential, five different mixed methanotrohic consortia (MMCs) were established from soil/sediment sources, i.e., landfill top cover soil, bio-solid compost, vegetated humus soil, estuarine and marine sediments. Enrichment conditions for MMCs were as follows: nitrate mineral salt (NMS) medium, pH ~ 6.8; 25 degrees C; 20-25 % CH4; agitation 200 rpm; and culture period 20 days, in mini-bench-top bioreactors. The enriched cultures were supplemented with extra carbon (methanol 0.5-1.5 %, formate 5-15 mM, and acetate 5-15 mM), nitrogen (nitrate 0.5-1.5 g L( 1), ammonium 0.1-0.5 g L(-1), or urea: 0.1-0.5 g L(-1)), and trace elements (copper 1-5 MUM, iron 1-5 MUM, and zinc 1-5 MUM) in different batch experiments to improve low-level CH4 abatement. Average CH4 oxidation capacities (MOCs) of MMCs varied between 1.712 +/- 0.032 and 1.963 +/- 0.057 mg g(-1)DWbiomass h(-1). Addition of formate improved the MOCs of MMCs, but the dose-response varied for different MMCs. Acetate, nitrate and copper had no significant effect on MOCs, while addition of methanol, ammonium, urea, iron and zinc impacted negatively. Overall, MMCs enriched from marine sediments and landfill top cover soil showed high MOCs which were largely resilient to nutrient supplementation, suggesting a strong potential for biofilter development for industrial low-level CH4 abatement, such as those present in CMV. PMID- 26867686 TI - Acute and short-term developmental toxicity of cyhalofop-butyl to zebrafish (Danio rerio). AB - Cyhalofop-butyl is an aryloxyphenoxypropionate post-emergence herbicide widely used around the world in agriculture. The acute toxicity of cyhalofop-butyl to embryos, larvae (12 and 72 h post-hatching), and adult zebrafish, as well as the short-term developmental toxicity of cyhalofop-butyl to embryo and sac-fry stages, was tested. The results showed that the 96-h LC50 values of cyhalofop butyl to embryos, 12 h post-hatching larvae, 72 h post-hatching larvae, and adult fish were 2.03, 0.58, 1.42, and 3.49 mg/L, respectively, suggesting zebrafish early life stages were more sensitive to cyhalofop-butyl than adult stage. Cyhalofop-butyl would inhibit the spontaneous movement, heartbeat, hatching rate of embryos, and the body length of surviving larvae of zebrafish at 1.00 mg/L or higher concentrations. Morphological abnormalities, including pericardial edema, yolk sac edema, deformation of tail, and deformation of spine, were induced by cyhalofop-butyl. The results indicated that cyhalofop-butyl had significant negative impacts on zebrafish at different life stages, and spontaneous movement and hatching rate were sensitive endpoints for assessing short-term developmental toxicity of cyhalofop-butyl. PMID- 26867687 TI - Effects of fullerene (C60), multi-wall carbon nanotubes (MWCNT), single wall carbon nanotubes (SWCNT) and hydroxyl and carboxyl modified single wall carbon nanotubes on riverine microbial communities. AB - Commercial production of nanoparticles (NP) has created a need for research to support regulation of nanotechnology. In the current study, microbial biofilm communities were developed in rotating annular reactors during continuous exposure to 500 MUg L(-1) of each nanomaterial and subjected to multimetric analyses. Scanning transmission X-ray spectromicroscopy (STXM) was used to detect and estimate the presence of the carbon nanomaterials in the biofilm communities. Microscopy observations indicated that the communities were visibly different in appearance with changes in abundance of filamentous cyanobacteria in particular. Microscale analyses indicated that fullerene (C60) did not significantly (p < 0.05) impact algal, cyanobacterial or bacterial biomass. In contrast, MWCNT exposure resulted in a significant decline in algal and bacteria biomass. Interestingly, the presence of SWCNT products increased algal biomass, significantly in the case of SWCNT-COOH (p < 0.05) but had no significant impact on cyanobacterial or bacterial biomass. Thymidine incorporation indicated that bacterial production was significantly reduced (p < 0.05) by all nanomaterials with the exception of fullerene. Biolog assessment of carbon utilization revealed few significant effects with the exception of the utilization of carboxylic acids. PCA and ANOSIM analyses of denaturing gradient gel electrophoresis (DGGE) results indicated that the bacterial communities exposed to fullerene were not different from the control, the MWCNT and SWNT-OH differed from the control but not each other, whereas the SWCNT and SWCNT-COOH both differed from all other treatments and were significantly different from the control (p < 0.05). Fluorescent lectin binding analyses also indicated significant (p < 0.05) changes in the nature and quantities of exopolymer consistent with changes in microbial community structure during exposure to all nanomaterials. Enumeration of protozoan grazers showed declines in communities exposed to fullerene or MWCNT but a trend for increases in all SWCNT exposures. Observations indicated that at 500 MUg L(-1), carbon nanomaterials significantly alter aspects of microbial community structure and function supporting the need for further evaluation of their effects in aquatic habitats. PMID- 26867688 TI - MicroRNA-1228(*) inhibit apoptosis in A549 cells exposed to fine particulate matter. AB - Studies have reported associations between fine particulate matter (PM2.5) and respiratory disorders; however, the underlying mechanism is not completely clear owing to the complex components of PM2.5. microRNAs (miRNAs) demonstrate tremendous regulation to target genes, which are sensitive to exogenous stimulation, and facilitate the integrative understood of biological responses. Here, significantly modulated miRNA were profiled by miRNA microarray, coupled with bioinformatic analysis; the potential biological function of modulated miRNA were predicted and subsequently validated by cell-based assays. Downregulation of miR-1228-5p (miR-1228(*)) expression in human A549 cells were associated with PM2.5-induced cellular apoptosis through a mitochondria-dependent pathway. Further, overexpression of miR-1228(*) rescued the cellular damages induced by PM2.5. Thus, our results demonstrate that PM2.5-induced A549 apoptosis is initiated by mitochondrial dysfunction and miR-1228(*) could protect A549 cells against apoptosis. The involved pathways and target genes might be used for future mechanistic studies. PMID- 26867689 TI - Enhanced nutrient removal from municipal wastewater assisted by mixotrophic microalgal cultivation using glycerol. AB - In a present study, nutrient removal from municipal wastewater by Chlorella vulgaris and Nannochloropsis oculata was investigated by using mixotrophic cultivation with glycerol (0 to 5 g/L). Performance parameters were assessed by estimating the removal of total nitrogen, total phosphorus, chemical oxygen demand (COD), biomass growth, chlorophyll content, lipid yield, and fatty acids. With the addition of 2 g/L glycerol, a maximum biomass productivity of 56 mg/L/day was achieved in the mixotrophic culture of C. vulgaris within 12 days. The mixotrophic culture showed a 30-fold increase in biomass productivity compared to the wastewater without any glycerol. However, the highest total nitrogen removal (80.62 %), total phosphate removal (60.72 %), and COD removal (96.3 %) was observed in the N. oculata culture supplemented with 3, 5, and 1 g/L glycerol, respectively. These results suggest that mixotrophic cultivation using glycerol offers great potential in the production of renewable biomass, waste water treatment, and consequent production of high-value microalgal oil. Graphical Abstract Simultaneous biomass production and nutrient removal using microalgae cultivated in wastewater supplemented with glycerol. PMID- 26867690 TI - Elemental analysis of soils and Salix polaris in the town of Pyramiden and its surroundings (Svalbard). AB - The contents of elements in the top soil (upper 5 cm) and deeper soil (5 to 10 cm) layers and in Salix polaris (leaves and stem) from the former Soviet mining town of Pyramiden and its close vicinity on the Svalbard archipelago were determined. The analyses covered major and trace elements, including heavy metals, in order to describe anthropogenic impacts related to the management of the mining town. Soil samples and plant tissues were analysed from 13 localities across and close to town vicinity. The plant ground cover of all sampling points was determined, and plant tissues (leaves and stem) were collected. Higher contents of Cd (3-11 mg kg(-1)) and Mo (11-33 mg kg(-1)) were detected in the soils. With relation to the world average concentration of metals in soils, the geo-accumulation indexes (Igeo) and the level of pollution of the analysed soils were classified into seven pollution grades. The soils of the studied localities were usually unpolluted (grade 1) when analysed for metals, with the soil pollution grades 4-6 identified only for Cd and Mo (moderately to strongly polluted). In Salix polaris, excessive amounts of Fe (60-1520 mg kg(-1)), Zn (80 1050 mg kg(-1)), Cd (0.2-5.5 mg kg(-1)) and Cr (0-3.6 mg kg(-1)) were observed. The Igeo of these elements, compared with values considered sufficient for plants, showed pollution grades from 2 to 6. The pollution load index (PLI) ranged between 0.49 and 1.01. Only one locality could be considered polluted having a PLI higher than 1. Plant/soil transfer factors (TF) for trace metals decreased in the following order: Zn > Cu > Cd > Mn > Ni > As > Mo > Pb > Co > Al > Cr > Fe. The principal contribution of this study consists in the assessment of the contamination of soils and plants by toxic heavy metals in an otherwise pristine environment of the Svalbard archipelago related to urban/industrial activities. PMID- 26867691 TI - WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF is characterized by epithelial cell injury and reprogramming, increases in (myo)fibroblasts, and altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) is involved in impaired epithelial mesenchymal crosstalk in pulmonary fibrosis. Here, we aimed to further investigate WISP1 regulation and function in primary human lung fibroblasts (phLFs). We demonstrate that WISP1 is directly upregulated by Transforming growth factor beta1 (TGFbeta1) and Tumor necrosis factor alpha (TNFalpha) in phLFs, using a luciferase-based reporter system. WISP1 mRNA and protein secretion increased in a time- and concentration-dependent manner by TGFbeta1 and TNFalpha in phLFs, as analysed by qPCR and ELISA, respectively. Notably, WISP1 is required for TGFbeta1- and TNFalpha-dependent induction of interleukin 6 (IL-6), a mechanism that is conserved in IPF phLFs. The siRNA-mediated WISP1 knockdown led to a significant IL-6 reduction after TGFbeta1 or TNFalpha stimulation. Furthermore, siRNA-mediated downregulation or antibody-mediated neutralization of WISP1 reduced phLFs proliferation, a process that was in part rescued by IL-6. Taken together, these results strongly indicate that WISP1-induced IL-6 expression contributes to the pro-proliferative effect on fibroblasts, which is likely orchestrated by a variety of profibrotic mediators, including Wnts, TGFbeta1 and TNFalpha. PMID- 26867692 TI - Hyaluronic acid versus saline intra-articular injections for amelioration of chronic knee osteoarthritis: A canine model. AB - The objective of this study was to assess the safety and efficacy of intra articular injections of hyaluronic acid (HA) versus saline for symptomatic treatment of osteoarthritis (OA). Twenty-five adult purpose-bred dogs underwent meniscal release of one knee. Clinical, arthroscopic, and radiographic signs of OA were confirmed in all dogs prior to treatment. Dogs were randomized into five groups: HA-1 (n = 5), HA-3 (n = 5), HA-5 (n = 5), Saline-1 (n = 5), and Saline-3 (n = 5). Each dog received intra-articular injections of the respective substance into the affected knee at the pre-determined time points. Dogs were assessed for heat, swelling, and erythema after each injection and for lameness, pain, effusion, range of motion, kinetics, radiographic OA scoring, and arthroscopic scoring prior to treatment and for 6 months after injection. Dogs were then humanely euthanatized and the knees assessed grossly and histologically. Only mild heat, swelling, and/or erythema were noted in some dogs following injection and resolved within 1 week. Dogs treated with HA-1, HA-3, and HA-5 were significantly (p < 0.05) better than dogs treated with Saline-1 and Saline-3 at the 4, 8, and 12 week time points based on at least one outcome measure. OA severity was not significantly different among groups at any time point, but increased in severity over time in all groups. Gross and histologic OA scores were not significantly different among groups. These data suggest the three HA injection protocols were safe, superior to saline for short-term amelioration of symptoms associated with chronic OA, and can be translated to human OA treatment. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1772-1779, 2016. PMID- 26867693 TI - Radiological impact of natural radionuclides from soils of Salamanca, Mexico. AB - Salamanca is the centre of a large industrial complex associated with the production and refining of oil-derived products in the state of Guanajuato, Mexico. The city also hosts a large chemical industry, and in past years a major fertilizer industry. All of them followed NORM (naturally occurring radioactive materials) industrial activities, where either raw materials or residues enriched in natural radionuclides are handled or generated, which can have an environmental radiological impact on their environmental compartments (e.g. soils and aquatic systems). In this study, activity concentrations of radionuclides from the 238U and 232Th natural series present in superficial urban soils surrounding an industrial complex in Salamanca, Mexico, have been determined to analyse the possible environmental radiological impact of some of the industrial activities. The alpha-particle and gamma-ray spectrometry is used for the radiometric characterization. The results revealed the presence of 10-42, 11-51 and 178-811Bq/kg of 238U, 232Th and 40K, respectively, without any clear anthropogenic increment in relation to the values normally found in unaffected soils. Thus, the radioactive impact of the industrial activities on the surrounding soils can be evaluated as very low, representing no radiological risk for the health of the population. PMID- 26867694 TI - Sequence diversity and ligand-induced structural rearrangements of viper hyaluronidase. AB - Hyaluronidases (Hyals) are a class of carbohydrate-active enzyme involved in angiogenesis, cancer proliferation, tumour growth and venom spreading. Functionally significant Hyals are responsible for the fast spreading of venom to the target site of action. The absence of molecular diversity and the structural and functional behaviour of snake venom Hyals was the inspiration for the objective of this study. Echis pyramidum leakeyi hyaluronidase (EHY)-based phylogenetic analysis showed the existence of two functional groups of Hyals which had diverged from the coral snake (the ancestor). The structure was modelled and it was found that the E-loop region (211-224 AA) was only present in EHY compared to the templates which may account for the significant function of viper Hyal. The best interacting ligands were screened from the selected plant derivatives and MYR consisted of better pharmacophore features (AADDRRR) in comparison with other ligands. Furthermore, the HOMO, LUMO, and MO energies and energy gaps of CGA, MIM and MYR were calculated by DFT analysis. EHY-ligand complex stability and interactions were investigated through MD simulation and FEL analysis. These revealed that MIM and MYR or their derivative compounds could be prominent lead molecules for both EHY and other eukaryotic Hyals. PCA analysis of both the non-ligated and ligated forms confirmed that loop-III (86-96 AA) and E-loop region structural rearrangements were essential for the association and dissociation process of the substrate. Particularly, ARG92 and LYS219 are determined as important key residues from the conformational changes. These regions' dynamic behaviour can be associated with HA binding and the catalytic function of EHY. This result can extend our knowledge of viper Hyal functional behaviour and provides structural insight to target eukaryotic Hyals as forthcoming drug targets in cancer treatment and venom spreading. PMID- 26867695 TI - Corrigendum: Pharmacologically targeted NMDA receptor antagonism by NitroMemantine for cerebrovascular disease. PMID- 26867696 TI - Monitoring of Vital Signs with Flexible and Wearable Medical Devices. AB - Advances in wireless technologies, low-power electronics, the internet of things, and in the domain of connected health are driving innovations in wearable medical devices at a tremendous pace. Wearable sensor systems composed of flexible and stretchable materials have the potential to better interface to the human skin, whereas silicon-based electronics are extremely efficient in sensor data processing and transmission. Therefore, flexible and stretchable sensors combined with low-power silicon-based electronics are a viable and efficient approach for medical monitoring. Flexible medical devices designed for monitoring human vital signs, such as body temperature, heart rate, respiration rate, blood pressure, pulse oxygenation, and blood glucose have applications in both fitness monitoring and medical diagnostics. As a review of the latest development in flexible and wearable human vitals sensors, the essential components required for vitals sensors are outlined and discussed here, including the reported sensor systems, sensing mechanisms, sensor fabrication, power, and data processing requirements. PMID- 26867699 TI - Intraoperative Predictors of Long-term Outcomes After Radiofrequency Endometrial Ablation. AB - STUDY OBJECTIVE: To identify intraoperative predictors of radiofrequency ablation (RFA) failure after adjusting for clinical risk factors. DESIGN: A cohort study (Canadian Task Force II-2). SETTING: An academic institution in the Upper Midwest. PATIENTS: Data were retrospectively collected from medical records of women who underwent RFA and who had a postprocedure gynecologic assessment between April 1998 and December 2011. INTERVENTIONS: RFA. MEASUREMENTS AND MAIN RESULTS: The primary outcome was RFA failure, which was defined as hysterectomy, repeat ablation, synechiolysis, or treatment with gonadotropin-releasing hormone analogue for postablation pain or bleeding. Cox proportional hazards regression was used to test the predictability of intraoperative variables on RFA failure with adjustment for baseline predictors. We created an RFA index to capture the procedure duration divided by the uterine surface area. One thousand one hundred seventy-eight women were eligible. The median age at ablation was 44 years (interquartile range, 40-48 years), and the median parity was 2 (interquartile range, 2-3). Dysmenorrhea and prior tubal ligation were reported in 37.1% and 37.2% of women, respectively. After adjustment for baseline characteristics, intraoperative predictors of failure were uterine sounding length >10.5 cm (adjusted hazard ratio [HR] = 2.58; 95% confidence interval [CI], 1.31-5.05), uterine cavity length >6 cm (adjusted HR = 2.06; 95% CI, 1.30-3.27), uterine width >4.5 cm (adjusted HR = 2.06; 95% CI, 1.29-3.28), surface area >25 cm(2) (adjusted HR = 2.02; 95% CI, 1.26-3.23), procedure time <93 seconds (adjusted HR = 2.61; 95% CI, 1.25-5.47), and RFA index <3.6 (adjusted HR = 3.14; 95% CI, 1.70 5.77). CONCLUSION: Intraoperative parameters are predictive of long-term adverse outcomes of RFA independent of patient clinical characteristics. Uterine length, procedure duration, and RFA index are associated with unfavorable outcomes and thus could be used to optimize postprocedure patient counseling. PMID- 26867698 TI - The efficacy of the appetite suppressant, diethylpropion, is dependent on both when it is given (day vs. night) and under conditions of high fat dietary restriction. AB - Obesity is a public health problem caused by excessive consumption of high caloric diets and/or lack of physical activity. Although treatments for obesity include low caloric diets and exercise programs, these activities frequently are supplemented with appetite suppressants. For the short-term treatment of weight loss, diethylpropion (DEP) is a commonly used appetite suppressant. However, little is known with regard to how to improve its weight loss efficacy. We therefore evaluated, in rats, two administration protocols where the animals received daily injections of DEP. First, when these nocturnal animals were normally active (at night) and when they were normally inactive (daytime), and second, with or without high fat dietary restriction (HFDR). We observed that DEP induced a greater weight-loss administered when the animals were in their active phase than in their inactive phase. Moreover, DEP's administration during the inactive phase (and to a lesser degree in the active phase) promotes the consumption of food during normal sleeping time. In addition, we found that DEP induced weight loss under ad libitum access to a HF diet, but its efficacy significantly improved under conditions of HFDR. In summary, the efficacy of DEP, and presumably other like appetite suppressants, is enhanced by carefully controlling the time it is administered and under dietary restriction of HF diets. PMID- 26867697 TI - Reduced reward-driven eating accounts for the impact of a mindfulness-based diet and exercise intervention on weight loss: Data from the SHINE randomized controlled trial. AB - Many individuals with obesity report over eating despite intentions to maintain or lose weight. Two barriers to long-term weight loss are reward-driven eating, which is characterized by a lack of control over eating, a preoccupation with food, and a lack of satiety; and psychological stress. Mindfulness training may address these barriers by promoting awareness of hunger and satiety cues, self regulatory control, and stress reduction. We examined these two barriers as potential mediators of weight loss in the Supporting Health by Integrating Nutrition and Exercise (SHINE) randomized controlled trial, which compared the effects of a 5.5-month diet and exercise intervention with or without mindfulness training on weight loss among adults with obesity. Intention-to-treat multiple mediation models tested whether post-intervention reward-driven eating and psychological stress mediated the impact of intervention arm on weight loss at 12 and 18-months post-baseline among 194 adults with obesity (BMI: 30-45). Mindfulness (relative to control) participants had significant reductions in reward-driven eating at 6 months (post-intervention), which, in turn, predicted weight loss at 12 months. Post-intervention reward-driven eating mediated 47.1% of the total intervention arm effect on weight loss at 12 months [beta = -0.06, SE(beta) = 0.03, p = .030, 95% CI (-0.12, -0.01)]. This mediated effect was reduced when predicting weight loss at 18 months (p = .396), accounting for 23.0% of the total intervention effect, despite similar weight loss at 12 months. Psychological stress did not mediate the effect of intervention arm on weight loss at 12 or 18 months. In conclusion, reducing reward-driven eating, which can be achieved using a diet and exercise intervention that includes mindfulness training, may promote weight loss (clinicaltrials.gov registration: NCT00960414). PMID- 26867700 TI - Laparoscopic Lateral Suspension: Benefits of a Cross-shaped Mesh to Treat Difficult Vaginal Vault Prolapse. AB - STUDY OBJECTIVE: To show an original technique of laparoscopic lateral suspension (LLS) with a precut mesh in a difficult case of vaginal vault prolapse. DESIGN: Step-by-step descriptions of the technique using videos (educational video). SETTING: Vaginal vault prolapse affects up to 1% of patients who had a hysterectomy. Sacrocolpopexy is considered the gold standard in the treatment of apical pelvic organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese patients or when an anatomic variation exists. This may be associated with rare but serious neurologic or ureteral morbidity as well as life-threatening vascular injury. LLS with mesh represents an alternative procedure, avoiding dissection at the promontory. The originality of this video is to describe the procedure of LLS in a difficult case of vaginal vault prolapse related to adhesions and difficulties of fascia cleavage. The use of a precut cross-shaped mesh simplified the technique and facilitated the attachment of the mesh to the fascia and the lateral suspension for a smaller period of time. This point is not negligible, especially in cases with technical difficulties. Institutional review board approval was obtained through the local ethics committee of Geneva University Hospitals (Canadian Task Force classification III). INTERVENTIONS: After dissections, positioning of the mesh on the dome and on the anterior and posterior vaginal walls is explained. The out-in technique of lateral suspension with the specific mesh is described. CONCLUSION: In this difficult case of vaginal vault prolapse, the LLS using a precut cross shaped mesh was placed in good conditions, providing the patient with a minimum risk of complications and with the benefits of minimally invasive approach. PMID- 26867702 TI - Tribute to: Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area [William Corrigall, Kathleen Coen and Laurel Adamson, Brain Res. 653 (1994) 278-284]. AB - In this paper, Dr. Corrigall and collaborators described elegant experiments designed to elucidate the neurobiology of nicotine reinforcement. The nicotinic receptor antagonist dihydro-beta-erythroidine (DHbetaE) was infused in the ventral tegmental area (VTA) or nucleus accumbens (NAC) of rats trained to self administer nicotine intravenously. Additionally, DHbetaE was infused in the VTA of rats trained to self-administer food or cocaine, and nicotine self administration was assessed in rats with lesions to the peduculopontine tegmental nucleus (PPT). A number of key themes emerged from this fundamental study that remain relevant today. The primary finding was that infusions of DHbetaE in the VTA, but not in the NAC, lowered nicotine self-administration, suggesting that nicotinic receptors in VTA are involved in the reinforcing action of nicotine. This conclusion has been confirmed by subsequent findings, and the nature of the nicotinic receptors has also been elucidated. The authors also reported that DHbetaE in the VTA had no effect on food or cocaine self-administration, and that lesions to the PPT did not alter nicotine self-administration. Since this initial investigation, the question of whether nicotinic receptors in the VTA are necessary for the reinforcing action of other stimuli, and by which mechanisms, has been extensively explored. Similarly, many groups have further investigated the role of mesopontine cholinergic nuclei in reinforcement. This paper not only contributed in important ways to our understanding of the neurochemical basis of nicotine reinforcement, but was also a key catalyst that gave rise to several research themes central to the neuropharmacology of substance abuse. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID- 26867701 TI - Peritoneal Washings After Power Morcellation in Laparoscopic Myomectomy: A Pilot Study. AB - STUDY OBJECTIVE: To evaluate if peritoneal washings of the abdominopelvic cavity during laparoscopic myomectomy can detect leiomyoma cells after power morcellation. DESIGN: Prospective cohort pilot study. SETTING: University of North Carolina Hospitals, an academic, tertiary referral center (Canadian Task Force classification II-2). PATIENTS: Patients undergoing laparoscopic or robotic myomectomy for suspected benign leiomyoma by members of the Minimally Invasive Gynecologic Surgery division between September 2014 and January 2015. INTERVENTION: Washings of the peritoneal cavity were collected at 3 times during surgery: the beginning of the procedure once the peritoneal cavity was accessed laparoscopically, after the myoma was excised and myometrial incision closed, and after uncontained power morcellation. MEASUREMENTS AND MAIN RESULTS: Twenty patients were included in the analysis. The median morcellation time was 16 minutes (range, 2-36). The median specimen weight was 283.5 g (range, 13-935). Cytologic evaluation (ThinPrep with Papanicolaou staining) did not detect any smooth muscle cells. Cell block histology, however, detected spindle cells in 6 postmorcellation samples. Three of these 6 cases also had spindle cells detected on the postmyomectomy closure samples. When performed on the postmorcellation samples, desmin and smooth muscle actin immunostaining were positive, confirming the presence of smooth muscle cells. CONCLUSION: Cell block histology, but not cytology, can detect leiomyoma cells in peritoneal washings after power morcellation. With myomectomy, there is some tissue disruption that seems to cause cell spread even in the absence of morcellation. Further protocol testing might allow peritoneal washings to be used in assessing containment techniques and testing comparative safety of different morcellation methods. PMID- 26867703 TI - The long pursued Holy Grail of the true "alcoholic" rat. AB - An anthology of microdialysis and electrophysiological studies on ethanol effect on mesolimbic dopaminergic neurons is presented. The usefulness of rats with innate preference for ethanol, such as the Sardinian alcohol-preferring (sP), in studying ethanol rewarding and reinforcing effects is signaled. The generation of the long sought "alcoholics rat" from sP rats is announced. Rats of the sP line avoid the shortcomings of using rats non selected for ethanol preference. PMID- 26867704 TI - Finding prefrontal cortex in the rat. AB - The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections The cortical projection field of the mediodorsal nucleus of the thalamus (MD) was identified in the rat using the Fink Heimer silver technique for tracing degenerating fibers. Small stereotaxic lesions confined to MD were followed by terminal degeneration in the dorsal bank of the rhinal sulcus (sulcal cortex) and the medial wall of the hemisphere anterior and dorsal to the genu of the corpus callosum (medial cortex). No degenerating fibers were traced to the convexity of the hemisphere. The cortical formation receiving a projection from MD is of a relatively undifferentiated type which had been previously classified as juxtallocortex. A study of the efferent fiber connections of the rat's MD-projection cortex demonstrated some similarities to those of monkey prefrontal cortex. A substantial projection to the pretectal area and deep layers of the superior colliculus originates in medial cortex, a connection previously reported for caudal prefrontal (area 8) cortex in the monkey. Sulcal cortex projects to basal olfactory structures and lateral hypothalamus, as does orbital frontal cortex in the monkey. The rat's MD projection cortex differs from that in the monkey in that it lacks a granular layer and appears to have no prominent direct associations with temporal and juxtahippocampal areas. Furthermore, retrograde degeneration does not appear in the rat thalamus after damage to MD-projection areas, suggesting that the striatum or thalamus receives a proportionally larger share of the MD-projection in this animal than it does in the monkey. Comparative behavioral investigations are in progress to investigate functional differences between granular prefrontal cortex in the primate and the relatively primitive MD-projection cortex in the rat. (c) 1969. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID- 26867705 TI - Online information for women and their families regarding reduced fetal movements is of variable quality, readability and accountability. AB - OBJECTIVE: reduced fetal movements (RFM) are experienced by 46-50% of women prior to the diagnosis of stillbirth. Empowering women with evidenced-based information regarding RFM may allow for prompt contact with a health care provider and access to appropriate management. Use of the Internet is growing in popularity as a source of pregnancy information to aid mothers' decision-making. This study aimed to identify and examine the available online information for pregnant women regarding RFM. DESIGN: a systematic search was performed using Google, Yahoo and Bing to identify the most popular websites giving information about RFM. The websites were assessed for readability, accountability and content using the Flesh-Kincaid ease of readability score; the Silberg criteria; and by comparison to evidence-based guidelines respectively. Chat forums were assessed using a qualitative thematic analysis. FINDINGS: 70 information articles and 63 chat forums were analysed from 77 unique websites. The mean readability score was 65.7 (suitable for the average 13-15 year old) and therefore above the recommended level set for health materials; only 15 (21.4%) websites met all accountability criteria; and 43 (70%) websites contained information that was not in accordance with evidence-based recommendations. Typical questions on forums were 'Is this normal? What should I do?' and responses were 'Better safe than sorry', 'There is no harm in calling'. KEY CONCLUSION: overall, there was wide variation in the quality of information regarding RFM on the Internet. However, the study identified four excellent websites on RFM that may be suitable sources of information for women. Women's uncertainty displayed in the chat forums may suggest that clearer, accessible guidance is needed if they experience RFM. IMPLICATIONS FOR PRACTICE: the Internet can compliment and support current methods of antenatal information provision. However, due to varying levels of quality it is essential that professionals discuss and direct women to useful evidenced-based websites. Care must be taken to ensure consistent advice and management of those presenting with RFM and that women's concerns are addressed. PMID- 26867706 TI - Survival in Children With Down Syndrome Undergoing Single-Ventricle Palliation. AB - BACKGROUND: We describe survival in patients with Down syndrome (DS) with single ventricle anatomy and palliation and characterize risk factors associated with mortality. METHODS: All patients with DS and single-ventricle anatomy documented in the electronic medical record at our institution from January 1, 1992, to May 1, 2014, were compared with patients with unbalanced atrioventricular septal defects and single-ventricle anatomy, without DS or heterotaxy, during the same period. Survival analysis was performed to evaluate factors associated with mortality, including the presence of DS. RESULTS: There were 28 patients with DS and 30 patients without DS. One-year survival with DS was 75% (95% CI: 55% to 87%); 5-year survival was 61% (95% CI: 40% to 76%). All DS deaths except one occurred before 2 years of age. One-year non-DS survival was 93% (95% CI: 76% to 98%); 5-year survival was 85% (95% CI: 64% to 94%). Factors associated with death by univariable analysis included DS (p = 0.04), pulmonary vascular resistance (PVR) of at least 3 Wood units * meter(2) (WUm(2)) in the first year of life (p = 0.03), and moderate-to-severe atrioventricular valve regurgitation (p = 0.1). In combined analysis, when accounting for PVR of at least 3 WUm(2) (hazard ratio [HR] 9.8, 95% CI: 1.1 to 83.5, p = 0.04), DS was not associated with increased mortality (HR 1.5, 95% CI: 0.3 to 7.8, p = 0.66). No patient with DS with PVR less than 3 WUm(2) died. CONCLUSIONS: Children with DS and single-ventricle anatomy have excellent survival when PVR is less than 3 WUm(2) in the first year of life, with minimal mortality beyond 2 years of age. When accounting for PVR, DS alone is not associated with increased mortality in patients with single ventricle anatomy. PMID- 26867707 TI - Side-to-side variation in normal femoral morphology: 3D CT analysis of 122 femurs. AB - BACKGROUND: The contralateral femur is often used as reference for reconstruction in unilateral hip joint pathology. The objective of this study was to quantify the side-to-side variation in proximal femur. We hypothesized that significant side-to-side differences exist between left and right femur with implications for preoperative planning and leg length discrepancy following hip arthroplasty. MATERIALS AND METHODS: CT-based 3D femoral models were reconstructed for 122 paired femurs in 61 young healthy subjects (46.9+/-6.8 years) with no history of hip pathology. Side-to-side differences of several femoral morphologic parameters, including femoral head diameter, femoral anteversion, horizontal offset and femoral head center location, were compared and correlated with demographic factors using multiple linear regression. RESULTS: Significant side to-side differences (P<0.01) were found in femoral anteversion (4.3+/-3.8 degrees ; range: 0.2 degrees to 17.3 degrees ), horizontal offset (2.5+/-2.1mm; range: 0.1 to 10.3mm), and femoral head center location (7.1+/-3.8mm; range: 0.5 to 19.4mm). The difference in femoral anteversion was strongly correlated with the difference in neck diameter (R(2)=0.79), whereas the difference in horizontal femoral offset was highly correlated with the head diameter difference (R(2)=0.72). Femoral head center difference was correlated with the femoral anteversion, horizontal offset and neck-shaft-angle difference (R(2)=0.82). DISCUSSION: Relying on the anatomic landmarks of the contralateral femur during hip arthroplasty may not necessarily result in restoration of native anatomy and leg-length. Knowledge of the baseline side-to-side asymmetry could provide a range of error that would be tolerable following hip reconstruction. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Retrospective observational study. PMID- 26867708 TI - Patient-specific risk factors for infection in arthroplasty procedure. AB - All patients are not equally at risk when it comes to postoperative infections, whether the risks are related to the environment or the patient. Patient-specific infection risk factors for arthroplasty should be a focal point during the preoperative consultation as they impact the treatment decision. Eighty percent of patients have at least one modifiable infection risk factor. These risk factors must be corrected preoperatively whenever possible so that the patient is operated under the best possible conditions, with the lowest possible infection risk. The screenings and preoperative preparations are multidisciplinary but must also involve the patient. The information provided to the patient must match the patient's infectious risk profile. This lecture will review every infection risk factor, whether it is modifiable or not, and then suggest how the treatment decision should be adapted to each patient's infection risk. PMID- 26867709 TI - Smoking and alcohol behaviours in people following hip and knee arthroplasty: Data from the Osteoarthritis Initiative. AB - BACKGROUND: Smoking and alcohol consumption has a negative effect on overall health. Limited evidence has been presented as to how these health behaviours may change between pre- and postoperative intervals in the initial 12 months post arthroplasty. The purpose of this study was to address this uncertainty. HYPOTHESIS: Smoking and alcohol consumption differs between pre- and post-THA/TKA and it differs between non-arthroplasty cohorts. MATERIALS AND METHODS: Data from the Osteoarthritis Initiative (OAI), a population-based observational study in the USA, were gathered. In total, data from 287 people who had undergone THA or TKA from baseline to month 48 OAI follow-up assessments were analysed. Data on this cohort were compared to 287 age- and gender-matched people with osteoarthritis. Mean change from pre- to post-arthroplasty, and differences between arthroplasty and non-arthroplasty participants for smoking and alcohol consumption were assessed descriptively and through Wilcoxin-matched pairs test and Student t-tests (as appropriate). RESULTS: The lifetime prevalence of smoking was high for people who received THA (99%) and TKA (96%). Prevalence of current smoking significantly decreased from 5 to 3% across the THA and TKA cohort in the initial 12 months post-arthroplasty (P<0.05). Similarly, there was a statistically significant decrease in weekly alcohol consumption post arthroplasty for people who underwent THA and TKA (P<0.01), although the mean difference was only by 0.9 alcoholic drinks. The only statistically significant difference in smoking and alcohol consumption for arthroplasty to non arthroplasty participants was in weekly alcohol consumption, which was higher by 0.3 drinks in the non-arthroplasty cohort (P=0.04). CONCLUSIONS: Smoking and alcohol consumption decreased in the initial 12 months post-THA and TKA. This was not significantly different to an age- and gender-matched non-arthroplasty cohort. Whilst this is positive, a small group of patients still present with unhealthy lifestyle choices in relation to these behaviours post-arthroplasty. LEVEL OF EVIDENCE: Level III - prospective case control study. PMID- 26867710 TI - BRCA1 and BRCA2 Mutation Testing in Young Women With Breast Cancer. AB - IMPORTANCE: BRCA testing is recommended for young women diagnosed as having breast cancer, but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients. OBJECTIVES: To describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of data collected following the opening of the study to accrual from October 10, 2006, through December 31, 2014, as part of the Helping Ourselves, Helping Others: Young Women's Breast Cancer Study, an ongoing prospective cohort study. Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers. MAIN OUTCOMES AND MEASURES: Frequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation. RESULTS: A total of 780 (87.0%) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis (mean age at diagnosis, 35.3 vs 36.9 years for untested women; P < .001), with the frequency of testing increasing among women diagnosed from August 1, 2006, through December 31, 2013. Of 39 women who were diagnosed as having breast cancer in 2006, 30 (76.9%) reported testing. In 2007, a slightly lower percentage of women (87 of 124 [70.2%]) reported testing; however, the proportion tested increased each subsequent year, with 141 (96.6%) of 146 and 123 (95.3%) of 129 women diagnosed as having breast cancer in 2012 and 2013, respectively, reporting BRCA testing (P < .001). Among untested women, 37 (31.6%) of 117 did not report discussion of the possibility that they might have a mutation with a physician and/or genetic counselor, and 43 (36.8%) of 117 were thinking of testing in the future. A total of 248 (29.8%) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions; among these women, 76 (86.4%) of 88 mutation carriers and 82 (51.2%) of 160 noncarriers chose bilateral mastectomy (P < .001). Fewer women reported that systemic treatment decisions were influenced by genetic risk concern. CONCLUSIONS AND RELEVANCE: Rates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility, all young women with breast cancer should be counseled and offered genetic testing, consistent with the National Comprehensive Cancer Network guidelines. PMID- 26867712 TI - Inhaled Mannitol (Bronchitol) for Cystic Fibrosis. PMID- 26867711 TI - Characterization of SCO4439, a D-alanyl-D-alanine carboxypeptidase involved in spore cell wall maturation, resistance, and germination in Streptomyces coelicolor. AB - This work contributes to the understanding of cell wall modifications during sporulation and germination in Streptomyces by assessing the biological function and biochemical properties of SCO4439, a D-alanyl-D-alanine carboxypeptidase (DD CPase) constitutively expressed during development. SCO4439 harbors a DD-CPase domain and a putative transcriptional regulator domain, separated by a putative transmembrane region. The recombinant protein shows that DD-CPase activity is inhibited by penicillin G. The spores of the SCO4439::Tn5062 mutant are affected in their resistance to heat and acid and showed a dramatic increase in swelling during germination. The mycelium of the SCO4439::Tn5062 mutant is more sensitive to glycopeptide antibiotics (vancomycin and teicoplanin). The DD-CPase domain and the hydrophobic transmembrane region are highly conserved in Streptomyces, and both are essential for complementing the wild type phenotypes in the mutant. A model for the biological mechanism behind the observed phenotypes is proposed, in which SCO4439 DD-CPase releases D-Ala from peptidoglycan (PG) precursors, thereby reducing the substrate pool for PG crosslinking (transpeptidation). PG crosslinking regulates spore physical resistance and germination, and modulates mycelium resistance to glycopeptides. This study is the first demonstration of the role of a DD-CPase in the maturation of the spore cell wall. PMID- 26867713 TI - Synthetic biology for production of natural and new-to-nature terpenoids in photosynthetic organisms. AB - With tens of thousands of characterized members, terpenoids constitute the largest class of natural compounds that are synthesized by all living organisms. Several terpenoids play primary roles in the maintenance of cell membrane fluidity, as pigments or as phytohormones, but most of them function as specialized metabolites that are involved in plant resistance to herbivores or plant-environment interactions. Terpenoids are an essential component of human nutrition, and many are economically important pharmaceuticals, aromatics and potential next-generation biofuels. Because of the often low abundance in their natural source, as well as the demand for novel terpenoid structures with new or improved bioactivities, terpenoid biosynthesis has become a prime target for metabolic engineering and synthetic biology projects. In this review we focus on the creation of new-to-nature or tailor-made plant-derived terpenoids in photosynthetic organisms, in particular by means of combinatorial biosynthesis and the activation of silent metabolism. We reflect on the characteristics of different potential photosynthetic host organisms and recent advances in synthetic biology and discuss their utility for the (heterologous) production of (novel) terpenoids. PMID- 26867714 TI - Development and validation of a sensitive monoclonal antibody-based indirect competitive enzyme-linked immunosorbent assay for the determination of the aflatoxin M1 levels in milk. AB - A sensitive monoclonal antibody (mAb) against aflatoxin M1 (AFM1) was generated to quickly monitor the AFM1 residues in milk. Then, a mAb-based indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established that utilizes simple sample preparation and clean-up methods. The obtained 3D8 mAb, which is an IgG1 isotype mAb, displayed an IC50 value of 64.75 ng L(-1) for AFM1 and did not exhibit measurable cross-reactivity with other aflatoxins and antibiotics. The decision limit (CCalpha, alpha = 1%), detection capability (CCbeta, beta = 5%), and LOQ value for the AFM1 matrix calibration method were 24 ng L(-1), 27.5 ng L(-1), and 35 ng L(-1) in the milk matrices, respectively. The AFM1 recovery ranged from 85.3% to 107.6%. The CVs were less than 13.8%. A positive correlation (r > 0.99) was observed between the ic-ELISA and HPLC-MS/MS results. This ic-ELISA would be a useful tool for screening the AFM1 residues in milk. PMID- 26867715 TI - A prospective examination of Axis I psychiatric disorders in the first 5 years following moderate to severe traumatic brain injury. AB - BACKGROUND: Psychiatric disorders commonly emerge during the first year following traumatic brain injury (TBI). However, it is not clear whether these disorders soon remit or persist for long periods post-injury. This study aimed to examine, prospectively: (1) the frequency, (2) patterns of co-morbidity, (3) trajectory, and (4) risk factors for psychiatric disorders during the first 5 years following TBI. METHOD: Participants were 161 individuals (78.3% male) with moderate (31.2%) or severe (68.8%) TBI. Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV, administered soon after injury and 3, 6 and 12 months, and 2, 3, 4 and 5 years post-injury. Disorder frequencies and generalized estimating equations were used to identify temporal relationships and risk factors. RESULTS: In the first 5 years post-injury, 75.2% received a psychiatric diagnosis, commonly emerging within the first year (77.7%). Anxiety, mood and substance-use disorders were the most common diagnostic classes, often presenting co-morbidly. Many (56.5%) experienced a novel diagnostic class not present prior to injury. Disorder frequency ranged between 61.8 and 35.6% over time, decreasing by 27% [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.65-0.83] with each year post-injury. Anxiety disorders declined significantly over time (OR 0.73, 95% CI 0.63-0.84), whilst mood and substance-use disorder rates remained stable. The strongest predictors of post-injury disorder were pre-injury disorder (OR 2.44, 95% CI 1.41-4.25) and accident-related limb injury (OR 1.78, 95% CI 1.03 3.07). CONCLUSIONS: Findings suggest the first year post-injury is a critical period for the emergence of psychiatric disorders. Disorder frequency declines thereafter, with anxiety disorders showing greater resolution than mood and substance-use disorders. PMID- 26867716 TI - Excitation Dynamics in Hetero-bichromophoric Calixarene Systems. AB - In this work, the dynamics of electronic energy transfer (EET) in bichromophoric donor-acceptor systems, obtained by functionalizing a calix[4]arene scaffold with two dyes, was experimentally and theoretically characterized. The investigated compounds are highly versatile, due to the possibility of linking the dye molecules to the cone or partial cone structure of the calix[4]arene, which directs the two active units to the same or opposite side of the scaffold, respectively. The dynamics and efficiency of the EET process between the donor and acceptor units was investigated and discussed through a combined experimental and theoretical approach, involving ultrafast pump-probe spectroscopy and density functional theory based characterization of the energetic and spectroscopic properties of the system. Our results suggest that the external medium strongly determines the particular conformation adopted by the bichromophores, with a direct effect on the extent of excitonic coupling between the dyes and hence on the dynamics of the EET process itself. PMID- 26867717 TI - The dilemma of immune stimulation and suppression during depression: One step closer to a solution? PMID- 26867718 TI - Postoperative cognitive dysfunction and neuroinflammation; Cardiac surgery and abdominal surgery are not the same. AB - Postoperative cognitive dysfunction (POCD) is a debilitating surgical complication, with cardiac surgery patients at particular risk. To gain insight in the mechanisms underlying the higher incidence of POCD after cardiac versus non-cardiac surgery, systemic and central inflammatory changes, alterations in intraneuronal pathways, and cognitive performance were studied after cardiac and abdominal surgery in rats. Male Wistar rats were subjected to ischemia reperfusion of the upper mesenteric artery (abdominal surgery) or the left coronary artery (cardiac surgery). Control rats remained naive, received anesthesia only, or received thoracic sham surgery. Rats were subjected to affective and cognitive behavioral tests in postoperative week 2. Plasma concentrations of inflammatory factors, and markers for neuroinflammation (NGAL and microglial activity) and the BDNF pathway (BDNF, p38MAPK and DCX) were determined. Spatial memory was impaired after both abdominal and cardiac surgery, but only cardiac surgery impaired spatial learning and object recognition. While all surgical procedures elicited a pronounced acute systemic inflammatory response, NGAL and TNFalpha levels were particularly increased after abdominal surgery. Conversely, NGAL in plasma and the paraventricular nucleus of the hypothalamus and microglial activity in hippocampus and prefrontal cortex on postoperative day 14 were increased after cardiac, but not abdominal surgery. Both surgery types induced hippocampal alterations in BDNF signaling. These results suggest that POCD after cardiac surgery, compared to non-cardiac surgery, affects different cognitive domains and hence may be more extended rather than more severe. Moreover, while abdominal surgery effects seem limited to hippocampal brain regions, cardiac surgery seems associated with more wide spread alterations in the brain. PMID- 26867719 TI - Primary angiosarcoma of the breast. AB - Primary angiosarcoma (AS) of the breast is a rare neoplasia that is not related to radiation exposure. It represents less than 0.05% of all malignant breast tumors. This lesion is characterized by aggressive patterns and poor prognosis and by the absence of typical features at radiologic examination. Currently there are not evidence-based guidelines regarding surgical and adjuvant treatment for this tumor even though wide surgical resection followed by chemo- radiotherapy appears to improve both disease free survival and overall survival. The aim of this study was to analyze the available series of AS patients suggesting the most reliable treatment options for this rare neoplasia. PMID- 26867720 TI - Symptomatic annular pancreas in adult: Report of two different presentations and treatments and review of the literature. AB - Annular pancreas (AP) in adults is a rare embryologic abnormality detected after development of complications or as incidental finding. Diagnosis and treatment strategies for symptomatic adult AP remain controversial. We describe two different presentation of AP: a woman with a specific upper abdominal pain treated with medical therapy and a man with upper gastroenteric obstructive symptoms which underwent surgical duodeno-jejunal by-pass. English language literature about annular pancreas etiology, diagnosis and treatment was reviewed. No specific guidelines and protocols exist about management of AP, therefore, treatment and operative approaches must be individualized. In consideration of the possible post-operative complications, surgical treatment should be reserved in case of failure of conservative medical therapies. PMID- 26867721 TI - Spray Inlet Proton Transfer Reaction Mass Spectrometry (SI-PTR-MS) for Rapid and Sensitive Online Monitoring of Benzene in Water. AB - Rapid and sensitive monitoring of benzene in water is very important to the health of people and for environmental protection. A novel and online detection method of spray inlet proton transfer reaction mass spectrometry (SI-PTR-MS) was introduced for rapid and sensitive monitoring of trace benzene in water. A spraying extraction system was coupled with the self-developed PTR-MS. The benzene was extracted from the water sample in the spraying extraction system and continuously detected with PTR-MS. The flow of carrier gas and salt concentration in water were optimized to be 50 sccm and 20% (w/v), respectively. The response time and the limit of detection of the SI-PTR-MS for detection of benzene in water were 55 s and 0.14 MUg/L at 10 s integration time, respectively. The repeatability of the SI-PTR-MS was evaluated, and the relative standard deviation of five replicate determinations was 4.3%. The SI-PTR-MS system was employed for monitoring benzene in different water matrices, such as tap water, lake water, and wastewater. The results indicated that the online SI-PTR-MS can be used for rapid and sensitive monitoring of trace benzene in water. PMID- 26867722 TI - Words of Wisdom. Re: Primary Endoscopic Realignment of Urethral Disruption Injuries--A Double-Edged Sword? PMID- 26867723 TI - Words of Wisdom. Re: Finasteride Reduces the Risk of Bladder Cancer in a Large Prospective Screening Study. PMID- 26867724 TI - Words of Wisdom. Re: Nephron-sparing Techniques Independently Decrease the Risk of Cardiovascular Events Relative to Radical Nephrectomy in Patients with a T1a T1b Renal Mass and Normal Preoperative Renal Function. PMID- 26867725 TI - Words of Wisdom. Re: Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. PMID- 26867726 TI - Words of Wisdom. Re: Genomic Classifier Identifies Men with Adverse Pathology After Radical Prostatectomy Who Benefit from Adjuvant Radiation Therapy. PMID- 26867727 TI - Words of Wisdom. Re: Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. PMID- 26867728 TI - Dermabacter vaginalis sp. nov., isolated from human vaginal fluid. AB - A novel actinobacterial strain, AD1-86T, was isolated from the vaginal fluid of a Korean female and was characterized by a polyphasic approach. The strain was a facultatively anaerobic, Gram-stain-positive, non-spore-forming, non-motile, catalase-positive and oxidase-negative short rod. Colonies were creamy white, of low convexity and 1-2 mm in diameter after growth on DSM 92 agar plates at 37 degrees C for 2 days. The most closely related strains were Dermabacter hominis DSM 7083T and Helcobacillus massiliensis 6401990T (98.3 and 96.3 % 16S rRNA gene sequence similarity, respectively). The isolate grew optimally at 37 degrees C and pH 7 in the presence of 0.5% (w/v) NaCl. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the cell-wall hydrolysates contained ribose, galactose and glucose. The DNA G+C content was 62.6 mol% and the mean DNA DNA relatedness value of the isolate to D. hominis DSM 7083T was 31.1+/-3.0% (reciprocal: 48.2+/-5.3%). The major cellular fatty acids (>10%) were anteiso C17:0, anteiso-C15:0 and iso-C16:0, and the menaquinones were MK-9, MK-8 and MK 7. The polar lipid profile of strain AD1-86T consisted of diphosphatidylglycerol, phosphatidylglycerol, two aminolipids and a glycolipid. Data from this polyphasic study indicate that strain AD1-86T represents a novel species of the genus Dermabacter, for which the name Dermabacter vaginalis sp. nov. is proposed; the type strain is AD1-86T (=KCTC 39585T=DSM 100050T). PMID- 26867729 TI - Ovarian cancer mimics: how to avoid being fooled by extraovarian pelvic masses. AB - In our clinical experience, pelvic masses from a variety of anatomic sites may be misdiagnosed as ovarian cancer. This tendency to overdiagnose a rare disease probably reflects both its protean imaging appearance and concern for its potential morbidity and mortality. However, radiologists can better serve patients with an analytic approach to the anatomic and tissue features of pelvic masses. We review a range of ovarian cancer mimics and illustrate the radiologic reasoning enabling correct diagnosis. PMID- 26867730 TI - MRI texture analysis parameters of contrast-enhanced T1-weighted images of Crohn's disease differ according to the presence or absence of histological markers of hypoxia and angiogenesis. AB - PURPOSE: To investigate if texture analysis parameters of contrast-enhanced MRI differ according to the presence of histological markers of hypoxia and angiogenesis in Crohn's disease (CD). METHODS: Seven CD patients (mean age 38 (19 75), 3 male)) undergoing ileal resection underwent 3T MR enterography including axial ultrafast spoiled gradient-echo T1 post IV gadolinium chelate. Regions of interest were placed in bowel destined for resection and registered to trans mural histological sections (n = 28 across 7 bowel sections) via MRI of the resected specimen. Microvessel density (MVD) and staining for markers of hypoxia (HIF 1alpha) and angiogenesis (VEGF) were performed. Texture analysis features were derived utilizing an image filtration-histogram technique at spatial scaling factor (SSF) 0-6 mm, including mean, standard deviation, mean of positive pixels, entropy, kurtosis and skewness and compared according to the presence or absence of histological markers of hypoxia/angiogenesis using Mann-Whitney U/Kruskal Wallis tests and with the log of MVD using simple linear regression. RESULTS: Mean, standard deviation and mean of positive pixels were significantly lower in sections expressing VEGF. For example at SSF 6 mm, median (inter-quartile range) of mean, standard deviation and mean of positive pixels in those with VEGF expression were 150.1 (134.7), 132.4 (49.2) and 184.0 (91.4) vs. 362.5 (150.2), 216.3 (100.1) and 416.6 (80.0) in those without (p = 0.001, p = 0.004 and p = 0.001), respectively. There was a significant association between skewness and MVD (ratio 1.97 (1.15-3.41)) at SSF = 2 mm. CONCLUSIONS: Contrast-enhanced MRI texture analysis features significantly differ according to the presence or absence of histological markers of hypoxia and angiogenesis in CD. PMID- 26867731 TI - Handgrip strength measured by a dynamometer connected to a smartphone: a new applied health technology solution for the self-assessment of rheumatoid arthritis disease activity. AB - OBJECTIVE: The aim was to analyse the accuracy of a hand dynamometer connected to a smartphone to assess RA disease activity through the measurement of handgrip strength (HGS). METHODS: Eighty-two RA patients participated in this prospective study. Three types of HGS were assessed: power (Po), pinch (Pi) and tripod (T). An interactive mobile application was developed to capture grip measures. A unilinear regression analysis between HGS and DAS28 was performed. A multivariate regression analysis to identify independent variables related to HGS was also conducted. RESULTS: Sixty-three patients (76.8%) were female. Mean age was 61.3 years. At baseline, a negative correlation between the three HGS measures and DAS28 score was found, as follows: Po, r = -0.65 (95% CI: -0.76, -0.51, P < 0.001); Pi, r= -0.42 (95% CI: -0.59, -0.23, P < 0.001); and T, r = -0.47 (95% CI: -0.63, -0.29, P < 0.001). In a longitudinal analysis of 32 patients, a negative correlation between DeltaPo grip and DeltaDAS28 was found (r = -0.76, 95% CI: 0.88, -0.56). Po grip was independently correlated with male sex (95% CI: 1.49, 4.14, P = 0.002), whereas variables inversely correlated with Po grip were disease duration (95% CI: -2.71, -1.34, P = 0.03), patient global assessment (95% CI: -2.41, -1.1, P < 0.001) and CRP level (95% CI: -3.56, -1.08, P < 0.001). CONCLUSION: HGS assessed by a hand dynamometer connected to a smartphone represents an innovative health technology solution that could prompt the self assessment of RA disease activity in an outpatient setting. PMID- 26867732 TI - Phenotypic variability in patients with ADA2 deficiency due to identical homozygous R169Q mutations. AB - OBJECTIVE: To determine the genotype-phenotype association in patients with adenosine deaminase-2 (ADA2) deficiency due to identical homozygous R169Q mutations inCECR1 METHODS: We present a case series of nine ADA2-deficient patients with an identical homozygous R169Q mutation. Clinical and diagnostic data were collected and available MRI studies were reviewed. We performed genealogy and haplotype analyses and measured serum ADA2 activity. ADA2 activity values were correlated to clinical symptoms. RESULTS: Age of presentation differed widely between the nine presented patients (range: 0 months to 8 years). The main clinical manifestations were (hepato)splenomegaly (8/9), skin involvement (8/9) and neurological involvement (8/9, of whom 6 encountered stroke). Considerable variation was seen in type, frequency and intensity of other symptoms, which included aplastic anaemia, acute myeloid leukaemia and cutaneous ulcers. Common laboratory abnormalities included cytopenias and hypogammaglobulinaemia. ADA2 enzyme activity in patients was significantly decreased compared with healthy controls. ADA2 activity levels tended to be lower in patients with stroke compared with patients without stroke. Genealogical studies did not identify a common ancestor; however, based on allele frequency, a North-West European founder effect can be noted. Three patients underwent haematopoietic cell transplantation, after which ADA2 activity was restored and clinical symptoms resolved. CONCLUSION: This case series revealed large phenotypic variability in patients with ADA2 deficiency though they were homozygous for the same R169Q mutation inCECR1 Disease modifiers, including epigenetic and environmental factors, thus seem important in determining the phenotype. Furthermore, haematopoietic cell transplantation appears promising for those patients with a severe clinical phenotype. PMID- 26867733 TI - Two carbohydrate recognizing domains from Cycas revoluta leaf lectin show the distinct sugar-binding specificity-A unique mannooligosaccharide recognition by N terminal domain. AB - Cycas revoluta leaf lectin (CRLL) of mannose-recognizing jacalin-related lectin (mJRL) has two tandem repeated carbohydrate recognition domains, and shows the characteristic sugar-binding specificity toward high mannose-glycans, compared with other mJRLs. We expressed the N-terminal domain and C-terminal domain (CRLL N and CRLL-C) separately, to determine the fine sugar-binding specificity of each domain, using frontal affinity chromatography, glycan array and equilibrium dialysis. The specificity of CRLL toward high mannose was basically derived from CRLL-N, whereas CRLL-C had affinity for alpha1-6 extended mono-antennary complex type glycans. Notably, the affinity of CRLL-N was most potent to one of three Man 8 glycans and Man 9 glycan, whereas the affinity of CRLL-C decreased with the increase in the number of extended alpha1-2 linked mannose residue. The recognition of the Man 8 glycans by CRLL-N has not been found for other mannose recognizing lectins. Glycan array reflected these specificities of the two domains. Furthermore, it was revealed by equilibrium dialysis method that the each domain had two sugar-binding sites, similar with Banlec, banana mannose binding Jacalin-related lectin. PMID- 26867735 TI - Increased Depth and Breadth of Plasma Protein Quantitation via Two-Dimensional Liquid Chromatography/Multiple Reaction Monitoring-Mass Spectrometry with Labeled Peptide Standards. AB - Absolute quantitative strategies are emerging as a powerful and preferable means of deriving concentrations in biological samples for systems biology applications. Method development is driven by the need to establish new-and validate current-protein biomarkers of high-to-low abundance for clinical utility. In this chapter, we describe a methodology involving two-dimensional (2D) reversed-phase liquid chromatography (RPLC), operated under alkaline and acidic pH conditions, combined with multiple reaction monitoring (MRM)-mass spectrometry (MS) (also called selected reaction monitoring (SRM)-MS) and a complex mixture of stable isotope-labeled standard (SIS) peptides, to quantify a broad and diverse panel of 253 proteins in human blood plasma. The quantitation range spans 8 orders of magnitude-from 15 mg/mL (for vitamin D-binding protein) to 450 pg/mL (for protein S100-B)-and includes 31 low-abundance proteins (defined as being <10 ng/mL) of potential disease relevance. The method is designed to assess candidates at the discovery and/or verification phases of the biomarker pipeline and can be adapted to examine smaller or alternate panels of proteins for higher sample throughput. Also detailed here is the application of our recently developed software tool-Qualis-SIS-for protein quantitation (via regression analysis of standard curves) and quality assessment of the resulting data. Overall, this chapter provides the blueprint for the replication of this quantitative proteomic method by proteomic scientists of all skill levels. PMID- 26867734 TI - A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease. AB - Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG. PMID- 26867736 TI - Quantitative Analysis of the Sirt5-Regulated Lysine Succinylation Proteome in Mammalian Cells. AB - Lysine (Lys) succinylation is a recently discovered protein posttranslational modification pathway that is evolutionarily conserved from bacteria to mammals. It is regulated by Sirt5, a member of the class III histone deacetylases (HDACs) or the Sirtuins. Recent studies demonstrated that Lys succinylation and Sirt5 are involved in diverse cellular metabolic processes including urea cycle, ammonia transfer, and glucose metabolism. In this chapter, we describe the general protocol to identify Sirt5-regulated Lys succinylation substrates and a computational method to calculate the absolute modification stoichiometries of Lys succinylation sites. The strategy employs Stable Isotope Labeling of Amino acid in Cell culture (SILAC) and the immunoaffinity enrichment of Lys succinylated peptides to identify the Lys succinylation sites that are significantly upregulated in Sirt5 knockout mouse embryonic fibroblast cells. PMID- 26867738 TI - Label-Free Quantitation for Clinical Proteomics. AB - Label-free quantification (LFQ) has emerged as a viable option for quantitative LC-MS/MS-based proteomic analyses for use on the scale of hundreds of samples such as are encountered in clinical analysis. Notably, sample preparation, sample loading, HPLC separations, and mass spectrometric performance must be highly reproducible for this approach to be effective. The following protocols describe the key steps in the methods related to sample preparation and analysis for LC MS/MS-based label-free quantitation using standard data-dependent acquisition. PMID- 26867737 TI - Determining the Composition and Stability of Protein Complexes Using an Integrated Label-Free and Stable Isotope Labeling Strategy. AB - In biological systems, proteins catalyze the fundamental reactions that underlie all cellular functions, including metabolic processes and cell survival and death pathways. These biochemical reactions are rarely accomplished alone. Rather, they involve a concerted effect from many proteins that may operate in a directed signaling pathway and/or may physically associate in a complex to achieve a specific enzymatic activity. Therefore, defining the composition and regulation of protein complexes is critical for understanding cellular functions. In this chapter, we describe an approach that uses quantitative mass spectrometry (MS) to assess the specificity and the relative stability of protein interactions. Isolation of protein complexes from mammalian cells is performed by rapid immunoaffinity purification, and followed by in-solution digestion and high resolution mass spectrometry analysis. We employ complementary quantitative MS workflows to assess the specificity of protein interactions using label-free MS and statistical analysis, and the relative stability of the interactions using a metabolic labeling technique. For each candidate protein interaction, scores from the two workflows can be correlated to minimize nonspecific background and profile protein complex composition and relative stability. PMID- 26867740 TI - Mass Spectrometry-Based Quantitative O-GlcNAcomic Analysis. AB - The dynamic co- and post-translational modification (PTM) of proteins, O-linked beta-D-N-acetylglucosamine modification (O-GlcNAcylation) of serine/threonine residues is critical in many cellular processes, contributing to multiple physiological and pathological events. The term "O-GlcNAcome" refers to not only the complete set of proteins that undergo O-GlcNAcylation but also the O-GlcNAc status at individual residues, as well as the dynamics of O-GlcNAcylation in response to various stimuli. O-GlcNAcomic analyses have been a challenge for many years. In this chapter, we describe a recently developed approach for the identification and quantification of O-GlcNAc proteins/peptides from complex samples. PMID- 26867739 TI - Proteogenomic Methods to Improve Genome Annotation. AB - Annotation of protein coding genes in sequenced genomes has been routinely carried out using gene prediction programs guided by available transcript data. The advent of mass spectrometry has enabled the identification of proteins in a high-throughput manner. In addition to searching proteins annotated in public databases, mass spectrometry data can also be searched against conceptually translated genome as well as transcriptome to identify novel protein coding regions. This proteogenomics approach has resulted in the identification of novel protein coding regions in both prokaryotic and eukaryotic genomes. These studies have also revealed that some of the annotated noncoding RNAs and pseudogenes code for proteins. This approach is likely to become a part of most genome annotation workflows in the future. Here we describe a general methodology and approach that can be used for proteogenomics. PMID- 26867741 TI - Isolating and Quantifying Plasma HDL Proteins by Sequential Density Gradient Ultracentrifugation and Targeted Proteomics. AB - The sensitivity and specificity of tandem mass spectrometers have made targeted proteomics the method of choice for the precise simultaneous measurement of many proteins in complex mixtures. Its application to the relative quantification of proteins in high-density lipoproteins (HDL) that have been purified from human plasma has revealed potential mechanisms to explain the atheroprotective effects of HDL. We describe a moderate throughput method for isolating HDL from human plasma that uses sequential density gradient ultracentrifugation, the traditional method of HDL purification, and subsequent trypsin digestion and nanoflow liquid chromatography-tandem mass spectrometry to quantify 38 proteins in the HDL fraction of human plasma. To control for the variability associated with digestion, matrix effects, and instrument performance, we normalize the signal from endogenous HDL protein-associated peptides liberated during trypsin digestion to the signal from peptides liberated from stable isotope-labeled apolipoprotein A-I spiked in as an internal standard prior to digestion. The method has good reproducibility and other desirable characteristics for preclinical research. PMID- 26867742 TI - A Method for Label-Free, Differential Top-Down Proteomics. AB - Biomarker discovery in the translational research has heavily relied on labeled and label-free quantitative bottom-up proteomics. Here, we describe a new approach to biomarker studies that utilizes high-throughput top-down proteomics and is the first to offer whole protein characterization and relative quantitation within the same experiment. Using yeast as a model, we report procedures for a label-free approach to quantify the relative abundance of intact proteins ranging from 0 to 30 kDa in two different states. In this chapter, we describe the integrated methodology for the large-scale profiling and quantitation of the intact proteome by liquid chromatography-mass spectrometry (LC-MS) without the need for metabolic or chemical labeling. This recent advance for quantitative top-down proteomics is best implemented with a robust and highly controlled sample preparation workflow before data acquisition on a high resolution mass spectrometer, and the application of a hierarchical linear statistical model to account for the multiple levels of variance contained in quantitative proteomic comparisons of samples for basic and clinical research. PMID- 26867743 TI - Multiplexed Immunoaffinity Enrichment of Peptides with Anti-peptide Antibodies and Quantification by Stable Isotope Dilution Multiple Reaction Monitoring Mass Spectrometry. AB - Immunoaffinity enrichment of peptides using anti-peptide antibodies and their subsequent analysis by targeted mass spectrometry using stable isotope-labeled peptide standards is a sensitive and relatively high-throughput assay technology for unmodified and modified peptides in cells, tissues, and biofluids. Suppliers of antibodies and peptides are increasingly aware of this technique and have started incorporating customized quality measures and production protocols to increase the success rate, performance, and supply of the necessary reagents. Over the past decade, analytical biochemists, clinical diagnosticians, antibody experts, and mass spectrometry specialists have shared ideas, instrumentation, reagents, and protocols, to demonstrate that immuno-MRM-MS is reproducible across laboratories. Assay performance is now suitable for verification of candidate biomarkers from large scale discovery "omics" studies, measuring diagnostic proteins in plasma in the clinical laboratory, and for developing a companion assay for preclinical drug studies. Here we illustrate the process for developing these assays with a step-by-step guide for a 20-plex immuno-MRM-MS assay. We emphasize the need for analytical validation of the assay to insure that antibodies, peptides, and mass spectrometer are working as intended, in a multiplexed manner, with suitable assay performance (median values for 20 peptides: CV = 12.4% at 740 amol/MUL, LOD = 310 amol/MUL) for applications in quantitative biology and candidate biomarker verification. The assays described conform to Tier 2 (of 3) level of analytical assay validation (1), meaning that the assays are capable of repeatedly measuring sets of analytes of interest within and across samples/experiments and employ internal standards for each analyte for confident detection and precise quantification. PMID- 26867744 TI - High-Throughput Quantitative Proteomics Enabled by Mass Defect-Based 12-Plex DiLeu Isobaric Tags. AB - Isobaric labeling has become a popular technique for high-throughput, mass spectrometry (MS)-based relative quantification of peptides and proteins. However, widespread use of the approach for large-scale proteomics applications has been limited by the high cost of commercial isobaric tags. To address this, we have developed our own N,N-dimethyl leucine (DiLeu) multiplex isobaric tags as a cost-effective alternative that can be synthesized with ease using readily available isotopic reagents. When paired with high-resolution tandem mass (MS(n)) acquisition, mass defect-based DiLeu isobaric tags allow relative quantification of up to twelve samples in a single liquid chromatography (LC)-MS(2) experiment. Herein, we present detailed methods for synthesis of 12-plex DiLeu isobaric tags, labeling of complex protein digest samples, analysis by high-resolution nanoLC MS(n), and processing of acquired data. PMID- 26867745 TI - Isotopic N,N-Dimethyl Leucine (iDiLeu) for Absolute Quantification of Peptides Using a Standard Curve Approach. AB - Quantitative proteomics studies require an absolute quantification step to accurately measure changes in protein concentration. Absolute quantification using liquid chromatography-mass spectrometry (LC-MS) traditionally combines triple quadrupole instrumentation with stable isotope-labeled standards to measure protein concentrations via their enzymatically produced peptides. Chemical modification of peptides using labels like mass differential tags for relative and absolute quantification (mTRAQ) provides another route to determine protein quantities. This chapter describes a cost-effective and high-throughput chemical labeling method that utilizes five amine-reactive, isotopic N,N-dimethyl leucine (iDiLeu) reagents. These tags enable generation of four-point calibration curves in one LC-MS run to determine protein concentrations from labeled peptides. In particular, we provide a detailed workflow for protein quantification using the iDiLeu reagent that includes important considerations like labeling conditions and isotopic interference correction. PMID- 26867746 TI - Selecting Optimal Peptides for Targeted Proteomic Experiments in Human Plasma Using In Vitro Synthesized Proteins as Analytical Standards. AB - In targeted proteomics, the development of robust methodologies is dependent upon the selection of a set of optimal peptides for each protein-of-interest. Unfortunately, predicting which peptides and respective product ion transitions provide the greatest signal-to-noise ratio in a particular assay matrix is complicated. Using in vitro synthesized proteins as analytical standards, we report here an empirically driven method for the selection of said peptides in a human plasma assay matrix. PMID- 26867748 TI - Large-Scale and Deep Quantitative Proteome Profiling Using Isobaric Labeling Coupled with Two-Dimensional LC-MS/MS. AB - Comprehensive, quantitative information on abundances of proteins and their posttranslational modifications (PTMs) can potentially provide novel biological insights into diseases pathogenesis and therapeutic intervention. Herein, we introduce a quantitative strategy utilizing isobaric stable isotope-labeling techniques combined with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) for large-scale, deep quantitative proteome profiling of biological samples or clinical specimens such as tumor tissues. The workflow includes isobaric labeling of tryptic peptides for multiplexed and accurate quantitative analysis, basic reversed-phase LC fractionation and concatenation for reduced sample complexity, and nano-LC coupled to high resolution and high mass accuracy MS analysis for high confidence identification and quantification of proteins. This proteomic analysis strategy has been successfully applied for in-depth quantitative proteomic analysis of tumor samples and can also be used for integrated proteome and PTM characterization, as well as comprehensive quantitative proteomic analysis across samples from large clinical cohorts. PMID- 26867750 TI - Methods for SWATHTM: Data Independent Acquisition on TripleTOF Mass Spectrometers. AB - Data independent acquisition (DIA also termed SWATH) is an emerging technology in the field of mass spectrometry based proteomics. Although the concept of DIA has been around for over a decade, the recent advancements, in particular the speed of acquisition, of mass analyzers have pushed the technique into the spotlight and allowed for high-quality DIA data to be routinely acquired by proteomics labs. In this chapter we will discuss the protocols used for DIA acquisition using the Sciex TripleTOF mass spectrometers and data analysis using the Sciex processing software. PMID- 26867749 TI - Multiple and Selective Reaction Monitoring Using Triple Quadrupole Mass Spectrometer: Preclinical Large Cohort Analysis. AB - Multiple reaction monitoring (MRM), sometimes referred to as selective reaction monitoring (SRM), is a mass spectrometry method that can target selective peptides for the detection and quantitation of a protein. Compared to traditional ELISA, MRM assays have a number of advantages including ease in multiplexing several proteins in the same assay and independence from the necessity for high quality, expensive, and at times unreliable antibodies. Furthermore, MRM assays can be developed to quantify multiple proteoforms of a single protein allowing the quantification of allelic expression of a particular sequence polymorphism, protein isoform, as well as determining site occupancy of posttranslational modification(s). In this chapter, we describe our workflow for target peptide selection, assay optimization, and acquisition multiplexing. Our workflow is presented using the example of constrained MRM assays developed for the serum protein ApoL1 in its various proteoforms to highlight the specific technical considerations necessary for the difficult task of quantifying peptide targets based on highly specific amino acid sequences by MRM. PMID- 26867747 TI - Using the CPTAC Assay Portal to Identify and Implement Highly Characterized Targeted Proteomics Assays. AB - The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal (http://assays.cancer.gov) to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and posttranslational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories. PMID- 26867751 TI - Measurement of Phosphorylated Peptides with Absolute Quantification. AB - Mass spectrometry, when coupled to on-line separation such as liquid chromatography or capillary electrophoresis, enables the identification and quantification of protein expression and post-translational modification changes under diverse conditions. To date most of the methods for mass spectrometry-based quantification have either provided relative quantification information (e.g., comparison to a selected condition) or utilized one-point calibration curves, or calibration curves in a different biological matrix. Although these quantitative methods have been used to generate insight into the differences between biological samples, additional biological insight could be gained by accurately measuring the absolute quantity of selected proteins and protein modifications. To address this challenge, we have developed the MARQUIS (Multiplex Absolute Regressed Quantification with Internal Standards) method, designed to provide absolute quantification for potentially hundreds of peptides across multiple samples in a single analysis, using a multi-point internal calibration curve derived from synthetic, isotopically distinct standard peptides. PMID- 26867752 TI - Proteomic Analysis of Protein Turnover by Metabolic Whole Rodent Pulse-Chase Isotopic Labeling and Shotgun Mass Spectrometry Analysis. AB - The analysis of protein half-life and degradation dynamics has proven critically important to our understanding of a broad and diverse set of biological conditions ranging from cancer to neurodegeneration. Historically these protein turnover measures have been performed in cells by monitoring protein levels after "pulse" labeling of newly synthesized proteins and subsequent chase periods. Comparing the level of labeled protein remaining as a function of time to the initial level reveals the protein's half-life. In this method we provide a detailed description of the workflow required for the determination of protein turnover rates on a whole proteome scale in vivo. Our approach starts with the metabolic labeling of whole rodents by restricting all the nitrogen in their diet to exclusively nitrogen-15 in the form of spirulina algae. After near complete organismal labeling with nitrogen-15, the rodents are then switched to a normal nitrogen-14 rich diet for time periods of days to years. Tissues are harvested, the extracts are fractionated, and the proteins are digested to peptides. Peptides are separated by multidimensional liquid chromatography and analyzed by high resolution orbitrap mass spectrometry (MS). The nitrogen-15 containing proteins are then identified and measured by the bioinformatic proteome analysis tools Sequest, DTASelect2, and Census. In this way, our metabolic pulse-chase approach reveals in vivo protein decay rates proteome-wide. PMID- 26867754 TI - Novel small molecule inhibitors of the OLIG2 transcription factor: promising new therapeutics for glioblastoma. PMID- 26867753 TI - Choosing a Nursing Home: What Do Consumers Want to Know, and Do Preferences Vary across Race/Ethnicity? AB - OBJECTIVE: To identify what consumers want to know about nursing homes (NHs) before choosing one and to determine whether information preferences vary across race/ethnicity. DATA SOURCES/STUDY SETTING: Primary data were collected in Greater Boston (January 2013-February 2014) from community-dwelling, white, black, and Latino adults aged 65+ and 40-64 years, who had personal/familial experience with a NH admission or concerns about one. STUDY DESIGN: Eleven focus groups and 30 interviews were conducted separately by race/ethnicity and age group. PRINCIPAL FINDINGS: Participants wanted detailed information on the facility, policies, staff, and residents, such as location, staff treatment of residents, and resident conditions. They wanted a sense of the NH gestalt and were interested in feedback/reviews from residents/families. Black and Latino participants were especially interested in resident and staff racial/ethnic concordance and facility cultural sensitivity. Latino participants wanted information on staff and resident language concordance. CONCLUSIONS: Consumers want more information about NHs than what is currently available from resources like Nursing Home Compare. Report card makers can use these results to enhance their websites, and they should consider the distinct needs of different racial/ethnic groups. Future research should test methods for collecting and reporting resident and family feedback/reviews. PMID- 26867755 TI - Direct P-functionalization of azobenzene by a cationic phosphidozirconocene complex. AB - We report that the cationic phosphidozirconocene complex [(eta(5) C5H5)2Zr(PCy2)][CH3B(C6F5)3] (II) reacts with azobenzene, resulting in the expedient formation of Zr complex (2) bound to a tridentate PNN ligand. This reaction proceeds by a mechanism of cooperative nucleophilic substitution of hydrogen. The intermediate sigma(H) adduct (1) has been characterized by NMR spectroscopy. PMID- 26867757 TI - Voices unite to demand free healthcare for refugees in Germany. PMID- 26867759 TI - Making Medicine Precise and Personalized: What Can We Learn from the Past? PMID- 26867756 TI - Recurrent mutation in the crystallin alpha A gene associated with inherited paediatric cataract. AB - BACKGROUND: Cataract is a major cause of childhood blindness worldwide. The purpose of this study was to determine the genetic cause of paediatric cataract in a South Australian family with a bilateral lamellar paediatric cataract displaying variable phenotypes. CASE PRESENTATION: Fifty-one genes implicated in congenital cataract in human or mouse were sequenced in an affected individual from an Australian (Caucasian) family using a custom Ampliseq library on the Ion Torrent Personal Genome Machine. Reads were mapped against the human genome (hg19) and variants called with the Torrent Suite software. Variants were annotated to dbSNP 137 using Ion Reporter (IR 1.6.2) and were prioritised for validation if they were novel or rare and were predicted to be protein changing. We identified a previously reported oligomerization disrupting mutation, c.62G > A (p.R21Q), in the Crystallin alpha A (CRYAA) gene segregating in this three generation family. No other novel or rare coding mutations were detected in the known cataract genes sequenced. Microsatellite markers were used to compare the haplotypes between the family reported here and a previously published family with the same segregating mutation. Haplotype analysis indicated a potential common ancestry between the two South Australian families with this mutation. The work strengthens the genotype-phenotype correlations between this functional mutation in the crystallin alpha A (CRYAA) gene and paediatric cataract. CONCLUSION: The p.R21Q mutation is the most likely cause of paediatric cataract in this family. The recurrence of this mutation in paediatric cataract families is likely due to a familial relationship. PMID- 26867758 TI - Clinical Effectiveness of Hydralazine-Isosorbide Dinitrate Therapy in Patients With Heart Failure and Reduced Ejection Fraction: Findings From the Get With The Guidelines-Heart Failure Registry. AB - BACKGROUND: In clinical trials, hydralazine-isosorbide dinitrate (H-ISDN) for heart failure with reduced ejection fraction reduced morbidity and mortality among black patients and patients with intolerance to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The effectiveness of H ISDN in clinical practice is unknown. METHODS AND RESULTS: Using data from a clinical registry linked with Medicare claims, we examined the use and outcomes of H-ISDN between 2005 and 2011 among older patients hospitalized with heart failure and reduced ejection fraction. We adjusted for demographic and clinical characteristics using Cox proportional hazards models and inverse probability weighting. Among 4663 eligible patients, 22.7% of black patients and 18.2% of patients not on an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker were newly prescribed H-ISDN therapy at discharge. By 3 years, the cumulative incidence rates of mortality and readmission were similar between treated and untreated patients. After multivariable adjustment, 3-year outcomes remained similar for mortality [black patients: hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.75-1.13; other patients: HR, 0.93; 95% CI, 0.79 1.09], all-cause readmission (black patients: HR, 0.98; 95% CI, 0.84-1.13; other patients: HR, 1.02; 95% CI, 0.90-1.17), and cardiovascular readmission (black patients: HR, 0.99; 95% CI, 0.82-1.19; other patients: HR, 0.94; 95% CI, 0.81 1.09). A post hoc analysis of Medicare Part D data revealed low postdischarge adherence to therapy. CONCLUSIONS: Guideline-recommended initiation of H-ISDN therapy at hospital discharge was uncommon, and adherence was low. For both black patients and patients of other races, there were no differences in outcomes between those treated and untreated at discharge. PMID- 26867760 TI - The second highest chromosome count among vertebrates is observed in cultured sturgeon and is associated with genome plasticity. AB - BACKGROUND: One of the five basal actinopterygian lineages, the Chondrostei, including sturgeon, shovelnose, and paddlefish (Order Acipenseriformes) show extraordinary ploidy diversity associated with three rounds of lineage-specific whole-genome duplication, resulting in three levels of ploidy in sturgeon. Recently, incidence of spontaneous polyploidization has been reported among cultured sturgeon and it could have serious negative implications for the economics of sturgeon farming. We report the occurrence of seven spontaneous heptaploid (7n) Siberian sturgeon Acipenser baerii, which is a functional tetraploid species (4n) with ~245 chromosomes. Our aims were to assess ploidy level and chromosome number of the analysed specimens and to identify the possible mechanism that underlies the occurrence of spontaneous additional chromosome sets in their genome. RESULTS: Among 150 specimens resulting from the mating of a tetraploid (4n) A. baerii (~245 chromosomes) dam with a hexaploid (6n) A. baerii (~368 chromosomes) sire, 143 displayed a relative DNA content that corresponds to pentaploidy (5n) with an absolute DNA content of 8.98 +/- 0.03 pg DNA per nucleus and nuclear area of 35.3 +/- 4.3 MUm(2) and seven specimens exhibited a relative DNA content that corresponds to heptaploidy (7n), with an absolute DNA content of 15.02 +/- 0.04 pg DNA per nucleus and nuclear area of 48.4 +/- 5.1 MUm(2). Chromosome analyses confirmed a modal number of ~437 chromosomes in these heptaploid (7n) individuals. DNA genotyping of eight microsatellite loci followed by parental assignment confirmed spontaneous duplication of the maternal chromosome sets via retention of the second polar body in meiosis II as the mechanism for the formation of this unusual chromosome number and ploidy level in a functional tetraploid A. baerii. CONCLUSIONS: We report the second highest chromosome count among vertebrates in cultured sturgeon (~437) after the schizothoracine cyprinid Ptychobarbus dipogon with ~446 chromosomes. The finding also represents the highest documented chromosome count in Acipenseriformes, and the first report of a functional heptaploid (7n) genome composition in sturgeon. To our knowledge, this study provides the first clear evidence of a maternal origin for spontaneous polyploidization in cultured A. baerii. To date, all available data indicate that spontaneous polyploidization occurs frequently among cultured sturgeons. PMID- 26867761 TI - International guidelines for contrast-enhanced ultrasonography: ultrasound imaging in the new millennium. AB - The intent of this review is to discuss and comment on common clinical scenarios in which contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity. PMID- 26867762 TI - Increased ROM and high patient satisfaction after open arthrolysis: a follow-up study of 43 patients with posttraumatic stiff elbows. AB - BACKGROUND: Posttraumatic stiffness of the elbow is a common finding after elbow trauma. Restoration of motion in the posttraumatic stiff elbow is difficult, time consuming, and requires high patient compliance. We have evaluated the long-term effect of an open elbow arthrolysis in the posttraumatic stiff elbow. METHODS: We evaluated 43 patients (14 women, 29 men) with a median age of 47(16-78) years operated with open arthrolysis for a posttraumatic stiff elbow. The median follow up time was 41(12-204) months. The patients were hospitalized median 12(4-14) days, with daily physiotherapy and NSAID. 36 patients tolerated continuous passive motion (CPM) for 11(0-42) days. 35 patients had a well-functioning brachial plexus anesthesia for median 7(1-18) days. We used the paired 2-tailed T test in our statistical analysis. RESULTS: Preoperatively the patients had a median flexion of 110(30-160) degrees , extension 40(10-90) degrees , and the total flexion-extension sector (F/E) was 50(0-110) degrees . At follow-up the patients had a median flexion of 132(75-151) degrees and extension of 23(8-84) degrees , which indicate a median gain of 42(-50-114) degrees . The subjective functional scores (Mayo Elbow Score, EQ5D, Q-Dash, and VAS for pain) were satisfying, and most of the patients (81 %) would have done the operation once again knowing the outcome. We had 5 temporary ulnar neuropraxias, one became permanent and in addition ankylotic, one temporary radial neuropraxia, two superficial wound infections, and one transient hematoma. CONCLUSION: Open arthrolysis of the posttraumatic stiff elbow is associated with reliable clinical and functional long-term outcomes. PMID- 26867763 TI - Improving growth in preterm infants during initial hospital stay: principles into practice. AB - Despite recent innovations in nutritional care, postnatal growth failure between birth and hospital discharge remains a significant problem in preterm infants. Whether or not it is entirely preventable is unclear. What is clear is that feeding practices and growth outcomes vary widely between neonatal intensive care units (NICUs). This partly reflects lack of data in key areas but it also reflects inconsistent translation of principles into practice and limitations in the way infants are fed and growth monitored in the NICU. These issues will be reviewed, in the process underline the key roles that audit, standardised feeding protocol, individualised nutritional care and a nutritional support team play in improving outcome in these high-risk infants. PMID- 26867764 TI - A phase II study of Epirubicin in oxaliplatin-resistant patients with metastatic colorectal cancer and TOP2A gene amplification. AB - The overall purpose of this study is to provide proof of concept for introducing the anthracycline epirubicin as an effective, biomarker-guided treatment for metastatic colorectal cancer (mCRC) patients who are refractory to treatment with oxaliplatin-based chemotherapy and have TOP2A gene amplification in their tumor cells. BACKGROUND: Epirubicin is an anthracycline that targets DNA topoisomerase 2-alpha enzyme encoded by the TOP2A gene. It is used for treatment of several malignancies, but currently not in CRC. TOP2A gene amplifications predict improved efficacy of epirubicin in patients with breast cancer and thus could be an alternative option for patients with CRC and amplified TOP2A gene. We have previously analysed the frequency of TOP2A gene aberrations in CRC and found that 46.6% of these tumors had TOP2A copy gain and 2.0% had loss of TOP2A when compared to adjacent normal tissue. The TOP2A gene is located on chromosome 17 and when the TOP2A/CEN-17 ratio was applied to identify tumors with gene loss or amplifications, 10.5% had a ratio >= 1.5 consistent with gene amplification and 2.6% had a ratio <= 0.8 suggesting gene deletions. Based on these observations and the knowledge gained from treatment of breast cancer patients, we have initiated a prospective clinical, phase II protocol using epirubicin (90 mg/m2 iv q 3 weeks) in mCRC patients, who are refractory to treatment with oxaliplatin. METHODS/DESIGN: The study is an open label, single arm, phase II study, investigating the efficacy of epirubicin in patients with oxaliplatin refractory mCRC and with a cancer cell TOP2A/CEN-17 ratio >= 1.5. TOP2A gene amplification measured by fluorescence in situ hybridization. A total of 25 evaluable patients (15 + 10 in two steps) will be included (Simon's two-stage minimax design). Every nine weeks, response is measured by computed tomography imaging and evaluated according to RECIST 1.1. The primary end-point of the study is progression-free survival. TRIAL REGISTRATION: Eudract no. 2013-001648-79. PMID- 26867765 TI - UCA1 functions as a competing endogenous RNA to suppress epithelial ovarian cancer metastasis. AB - Urothelial cancer associated 1 (UCA1) is an example of functional long noncoding RNAs involved in many biologic processes. However, little is known about the association between UCA1 expression and metastasis in epithelial ovarian cancer (EOC). Findings of this study confirmed that not only UCA1 was aberrantly upregulated in EOC tissues and cells, but also correlated with status of lymph node metastasis and FIGO stage. Furthermore, univariate and multivariate analyses showed that UCA1 was a prognostic factor for overall survival in EOC patients. In vitro, knockdown of UCA1 reduced the invasion and migration ability of EOC cells. The results showed that UCA1 could function as an endogenous sponge by directly binding to miR-485-5p. Depletion of UCA1 was involved in the downregulation of matrix metallopeptidase 14 (MMP14) expression, a target gene of miR-485-5p. In conclusion, our work indicates that UCA1 is a new prognostic biomarker for EOC, establishing a novel connection among UCA1, miR-485-5p, and MMP14 in EOC metastasis. PMID- 26867766 TI - iRGD-targeted delivery of a pro-apoptotic peptide activated by cathepsin B inhibits tumor growth and metastasis in mice. AB - The use of cytolytic peptides with potential therapeutic properties is a promising approach to cancer therapy due to their convenient automated synthesis and their capacity for modifications. However, the use of cytolytic peptides is limited due to their nonspecific cytolytic activity. In this study, we designed a tumor-targeting proapoptotic system based on an amphipathic D-amino acid-modified apoptotic peptide, KLA, a variant of (KLAKLAK)2, which is fused with a linear tumor-penetrating homing peptide iRGD through specific cathepsin B (CTSB) cleavage sequences that are overexpressed in many types of tumor tissues. Our data show that the procytotoxic peptide D(KLAKLAKKLAKLA)K-GG-iRGD (m(KLA)-iRGD) is internalized into cultured tumor cells through a neuropilin-1 (NRP1)-activated pathway by iRGD delivery. Once inside the cells, the peptide triggers rapid apoptosis through both the mitochondrial-induced apoptotic pathway and the death receptor pathway in NRP1+/alphavbeta3/CTSB+ tumor cells. Furthermore, m(KLA)-iRGD spread extensively within the tumor tissue when it was injected into 4T1 tumor bearing mice. The m(KLA)-iRGD peptide inhibited tumor growth to a certain degree, resulting in a significant reduction in tumor volume (P < 0.05) and the total inhibition of metastasis at the end of the treatment. These results suggest that m(KLA)-iRGD has the potential for development as a new antitumor drug. PMID- 26867768 TI - A truncated phosphorylated p130Cas substrate domain is sufficient to drive breast cancer growth and metastasis formation in vivo. AB - Elevated p130Cas (Crk-associated substrate) levels are found in aggressive breast tumors and are associated with poor prognosis and resistance to standard therapeutics in patients. p130Cas signals majorly through its phosphorylated substrate domain (SD) that contains 15 tyrosine motifs (YxxP) which recruit effector molecules. Tyrosine phosphorylation of p130Cas is important for mediating migration, invasion, tumor promotion, and metastasis. We previously developed a Src*/SD fusion molecule approach, where the SD is constitutively phosphorylated. In a polyoma middle T-antigen (PyMT)/Src*/SD double-transgenic mouse model, Src*/SD accelerates PyMT-induced tumor growth and promotes a more aggressive phenotype. To test whether Src*/SD also drives metastasis and which of the YxxP motifs are involved in this process, full-length and truncated SD molecules fused to Src* were expressed in breast cancer cells. The functionality of the Src*/SD fragments was analyzed in vitro, and the active proteins were tested in vivo in an orthotopic mouse model. Breast cancer cells expressing the full-length SD and the functional smaller SD fragment (spanning SD motifs 6-10) were injected into the mammary fat pads of mice. The tumor progression was monitored by bioluminescence imaging and caliper measurements. Compared with control animals, the complete SD promoted primary tumor growth and an earlier onset of metastases. Importantly, both the complete and truncated SD significantly increased the occurrence of metastases to multiple organs. These studies provide strong evidence that the phosphorylated p130Cas SD motifs 6-10 (Y236, Y249, Y267, Y287, and Y306) are important for driving mammary carcinoma progression. PMID- 26867767 TI - Colchicine induces autophagy and senescence in lung cancer cells at clinically admissible concentration: potential use of colchicine in combination with autophagy inhibitor in cancer therapy. AB - Colchicine is a well-known and potent microtubule targeting agent, but the therapeutic value of colchicine against cancer is limited by its toxicity against normal cells. But, there is no report of its cytotoxic potential against lung cancer cell, at clinically permissible or lower concentrations, minimally toxic to non-cancerous cells. Hence, in the present study, we investigated the possible mechanism by which the efficacy of colchicine against lung cancer cells at less toxic dose could be enhanced. Colchicine at clinically admissible concentration of 2.5 nM had no cytotoxic effect and caused no G2/M arrest in A549 cells. However, at this concentration, colchicine strongly hindered the reformation of cold depolymerised interphase and spindle microtubule. Colchicine induced senescence and reactive oxygen species mediated autophagy in A549 cells at this concentration. Autophagy inhibitor 3-methyladenine (3-MA) sensitised the cytotoxicity of colchicine in A549 cells by switching senescence to apoptotic death, and this combination had reduced cytotoxicity to normal lung fibroblast cells (WI38). Together, these findings indicated the possible use of colchicine at clinically relevant dose along with autophagy inhibitor in cancer therapy. PMID- 26867769 TI - Association between the CpG island methylator phenotype and its prognostic significance in primary pulmonary adenocarcinoma. AB - Aberrant methylation of promoter CpG islands is one of the most important inactivation mechanisms for tumor suppressor and tumor-related genes. Previous studies using genome-wide DNA methylation microarray analysis have suggested the existence of a CpG island methylator phenotype (CIMP) in lung adenocarcinomas. Although the biological behavior of these tumors varies according to tumor stage, no large-scale study has examined the CIMP in lung adenocarcinoma patients according to tumor stage. Furthermore, there have been no reported results regarding the clinical significance of each of the six CIMP markers. To examine the CIMP in patients with pulmonary adenocarcinoma after a surgical resection, we performed methylation analysis of six genes (CCNA1, ACAN, GFRA1, EDARADD, MGC45800, and p16 (INK4A)) in 230 pulmonary adenocarcinoma cases using the SEQUENOM MassARRAY platform. Fifty-four patients (28 %, 54/191) were in the CIMP high (CIMP-H) group associated with high nodal stage (P = 0.007), the presence of micropapillary or solid histology (P = 0.003), and the absence of an epidermal growth factor receptor (EGFR) mutation (P = 0.002). By multivariate analysis, CIMP was an independent prognostic marker for overall survival (OS) and disease specific survival (P = 0.03 and P = 0.43, respectively). In the stage I subgroups alone, CIMP-H patients had lower OS rates than the CIMP-low (CIMP-L) group (P = 0.041). Of the six CIMP markers, ACAN alone was significantly associated with patient survival. CIMP predicted the risk of progression independently of clinicopathological variables and enables the stratification of pulmonary adenocarcinoma patients, particularly among stage I cases. PMID- 26867770 TI - Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL. AB - Cathepsin D (CD), a ubiquitously expressed lysosomal aspartic protease, is upregulated in human breast carcinoma and many other tumor types. CD has been repeatedly reported to act as key mediator of apoptosis induced by various chemotherapeutics. However, there is still controversy over the role of enzymatic/proteolytic versus protein-protein interaction activities of CD in apoptotic signaling. The elucidation of molecular mechanism responsible for the effect of CD in the chemotherapy-induced cell death is crucial for development of an appropriate strategy to target this protease in cancer treatment. Therefore, the objective of this study was to investigate the molecular mechanism behind the CD-mediated regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death. For this purpose, MDA-MB-231 breast carcinoma cells with an increased level of wt CD (CD) or mutant enzymatically inactive CD (DeltaCD) were subjected to TRAIL and the frequency of apoptosis was determined. Our results show that CD facilitates the TRAIL-induced apoptosis of MDA-MB-231 breast cancer cells in enzymatic activity-dependent manner. Moreover, the importance of endosomal/lysosomal acidification in this process was documented. Analysis of the potential substrates specifically cleaved by CD during the TRAIL induced apoptosis confirmed caspase-8 and Bid proteins as the CD targets. Moreover, in search for protein regulators of apoptosis that can be cleaved by CD at physiologically relevant pH, we identified the Bcl-2 protein as a suitable candidate. The modulatory role of CD in cell response to TRAIL was also confirmed in another breast cancer cell line SKBR3. These experiments identified the CD enzymatic activity as a new factor affecting sensitivity of breast cancer cells to TRAIL. PMID- 26867772 TI - Exosomal miRNAs as biomarkers of recurrent lung cancer. AB - Prognosis of lung cancer still remains grim largely due to recurrence and aggressive metastasis of the disease. In this study, we examined the potential of exosomal miRNAs as biomarkers of recurrent lung cancer. Initially, in vitro miRNA profiles of normal lung (Beas-2b) and lung cancer (H1299) cells and of exosomes isolated from conditioned media were determined. In vivo study involved establishing subcutaneous primary and recurrent lung cancer xenografts in nude mouse model and examining tumor and serum exosomal miRNA alteration in secondary/recurrent lung tumors. A total of 77 miRNAs were observed to be significantly modulated in the H1299 cells (47 miRNA upregulated and 30 downregulated) compared to the Beas-2b cells. The exosomes isolated from conditioned media indicated several miRNAs which were in agreement with cells of origin. A similarity was also observed between miRNAs from serum exosomes and tumors, indicating their origin from the lung tumors. Two miRNAs, miR-21 and miR 155, were found to be significantly upregulated in recurrent tumors compared to primary tumors. These miRNAs were also upregulated in serum exosomes of recurrent tumor-bearing animals versus non-tumor- or primary tumor-bearing animals. Increased expression of the recurrent disease markers were also observed in recurrent tumors compared with primary tumors. Serum exosomes from recurrent tumor mice mirrored its tumor profile in expressing higher levels of these proteins compared with exosomes from primary tumor mice. Our data suggest that exosomal miRNA signatures may be a true representation of a pathological profile of lung cancer; thus, miRNAs could serve as promising biomarkers for non-invasive diagnosis of the disease. PMID- 26867773 TI - Recovery of symbiotic nitrogen fixing acacia rhizobia from Merzouga Desert sand dunes in South East Morocco--Identification of a probable new species of Ensifer adapted to stressed environments. AB - Bacteria capable of nodulating Acacia tortilis and A. gummifera could be recovered from sand dunes collected in the Moroccan Merzouga desert. The trapping approach enabled the recovery of 17 desert rhizobia that all clustered within the Ensifer (Sinorhizobium) genus. Four isolates of the dominant genotype comprising 15 strains as well as 2 divergent strains were further characterized by MLSA. Phylogenetic analyzes indicated that the dominant genetic type was belonging to a new and yet undefined species within the Ensifer genus. Interestingly, housekeeping gene phylogenies showed that this possibly new species is also present in another desert but in India. Phylogenetic analyses of nifH and nodC sequences showed high sequence conservation among the Moroccan strains belonging to the dominant genotype but high divergence with sequences from Indian isolates suggesting acquisition of symbiotic genes through Horizontal Gene Transfer. These desert rhizobia were capable of growing in media containing high salt concentrations, under high pH and most of the strains showed growth at 45 degrees C. Only recovered from desert type of Biome, yet, this new taxon appears particularly adapted to such harsh environment. PMID- 26867771 TI - The MDM4 SNP34091 (rs4245739) C-allele is associated with increased risk of ovarian-but not endometrial cancer. AB - The MDM4 protein (also known as MDMX or HDMX) is a negative regulator of p53, not only by direct interaction but also through its interaction with MDM2. Further, MDM4 overexpression and amplification have been observed in several cancer forms. Recently, a single nucleotide polymorphism (SNP) in the 3' untranslated region of the MDM4 gene, SNP34091A > C (rs4245739) was reported to alter MDM4 messenger RNA (mRNA) stability by modulating a microRNA binding site, thereby leading to decreased MDM4 levels. In this case-control study, we aimed to evaluate the possible association between MDM4 SNP34091 status and cancer risk by comparing the genotype frequencies in large hospital-based cohorts of endometrial- (n = 1404) and ovarian (n = 1385) cancer patients with healthy female controls (n = 1870). Genotype frequencies were compared by odds ratio (OR) estimates and Fisher exact tests. We found that individuals harboring the MDM4 SNP34091AC/CC genotypes had a significantly elevated risk for serous ovarian cancer (SOC) in general and high-grade serous ovarian cancer (HGSOC) in particular (SOC: OR = 1.18., 95 % CI = 1.01-1.39; HGSOC: OR = 1.25, CI = 1.02-1.53). No association between SNP34091 genotypes and endometrial cancer risk was observed. Our data indicate the MDM4 SNP34091AC/CC genotypes to be associated with an elevated risk for SOC and in particular the HGSOC type. PMID- 26867775 TI - Meta-Analysis With a Continuous Covariate That Is Differentially Categorized Across Studies. AB - We propose taking advantage of methodology for missing data to estimate relationships and adjust outcomes in a meta-analysis where a continuous covariate is differentially categorized across studies. The proposed method incorporates all available data in an implementation of the expectation-maximization algorithm. We use simulations to demonstrate that the proposed method eliminates bias that would arise by ignoring a covariate and generalizes the meta-analytical approach for incorporating covariates that are not uniformly categorized. The proposed method is illustrated in an application for estimating diarrhea incidence in children aged <=59 months. PMID- 26867774 TI - Spatial heterogeneity of malaria in Ghana: a cross-sectional study on the association between urbanicity and the acquisition of immunity. AB - BACKGROUND: Malaria incidence has declined considerably over the last decade. This is partly due to a scale-up of control measures but is also attributed to increasing urbanization. This study aimed to analyse the association between malaria and urbanization and the effect of urbanicity on the acquisition of semi immunity. METHODS: In 2012, children with fever presenting to St Michael's Hospital Pramso/Ghana were recruited. The malaria-positive-fraction (MPF) of fever cases was calculated on community-level to approximate the malaria risk. The mean age of malaria cases was calculated for each community to estimate the acquisition of semi-immunity. The level of urbanicity for the communities was calculated and associations between MPF, urbanicity and immunity were modelled using linear regression. RESULTS: Twenty-six villages were included into the study with a mean MPF of 35 %. A linear decrease of 5 % (95 % CI: 4-6 %) in MPF with every ten-point increase in urbanicity was identified. The mean age of malaria patients increased by 2.9 months (95 % CI: 1.0-4.8) with every ten-point increase in urbanicity. DISCUSSION: The results confirm an association between an increase in urbanicity and declining malaria risk and demonstrate that the acquisition of semi-immunity is heterogeneous on a micro-epidemiological scale and is associated with urbanicity. PMID- 26867776 TI - Statistical Reasoning and Methods in Epidemiology to Promote Individualized Health: In Celebration of the 100th Anniversary of the Johns Hopkins Bloomberg School of Public Health. AB - Epidemiology is concerned with determining the distribution and causes of disease. Throughout its history, epidemiology has drawn upon statistical ideas and methods to achieve its aims. Because of the exponential growth in our capacity to measure and analyze data on the underlying processes that define each person's state of health, there is an emerging opportunity for population-based epidemiologic studies to influence health decisions made by individuals in ways that take into account the individuals' characteristics, circumstances, and preferences. We refer to this endeavor as "individualized health." The present article comprises 2 sections. In the first, we describe how graphical, longitudinal, and hierarchical models can inform the project of individualized health. We propose a simple graphical model for informing individual health decisions using population-based data. In the second, we review selected topics in causal inference that we believe to be particularly useful for individualized health. Epidemiology and biostatistics were 2 of the 4 founding departments in the world's first graduate school of public health at Johns Hopkins University, the centennial of which we honor. This survey of a small part of the literature is intended to demonstrate that the 2 fields remain just as inextricably linked today as they were 100 years ago. PMID- 26867777 TI - Epidemiology and the Tobacco Epidemic: How Research on Tobacco and Health Shaped Epidemiology. AB - In this article, I provide a perspective on the tobacco epidemic and epidemiology, describing the impact of the tobacco-caused disease epidemic on the field of epidemiology. Although there is an enormous body of epidemiologic evidence on the associations of smoking with health, little systematic attention has been given to how decades of research have affected epidemiology and its practice. I address the many advances that resulted from epidemiologic research on smoking and health, such as demonstration of the utility of observational designs and important parameters (the odds ratio and the population attributable risk), guidelines for causal inference, and systematic review approaches. I also cover unintended and adverse consequences for the field, including the strategy of doubt creation and the recruitment of epidemiologists by the tobacco industry to serve its mission. The paradigm of evidence-based action for addressing noncommunicable diseases began with the need to address the epidemic of tobacco caused disease, an imperative for action documented by epidemiologic research. PMID- 26867778 TI - Manual thrombus aspiration during primary percutaneous coronary intervention: Impact of total ischemic time. AB - BACKGROUND: The benefit of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) remains uncertain, and the effect of TA in relation to total ischemic time has not been evaluated. METHODS: We analyzed 5641 patients with ST-elevation myocardial infarction (STEMI) (<12h) from the Korea Acute Myocardial Infarction Registry undergoing primary PCI. Patients were divided into 2 groups: TA (n=1245) and PCI only (n=4396). Propensity-matched 12 month clinical outcome was compared between the groups according to different total ischemic times (<=2h, 2-4h, 4-6h, >6h). RESULTS: Twelve-month rates of death and major adverse cardiac events (MACE: composite of death, recurrent myocardial infarction, target-vessel revascularization, and coronary artery bypass grafting) were not different between TA and PCI only. After propensity matching (n=1162 for each group), there were no differences in the 12-month outcome between TA and PCI only, which was consistent across subgroups. In the propensity-matched cohort, the effect of TA on 12-month outcome showed a U-shaped relationship with longer total ischemic time: TA in patients with total ischemic time between 4 and 6h was associated with lower rates of death [hazard ratio (HR): 0.53, 95% confidence interval (CI): 0.24-1.19, p for interaction=0.01] and MACE (HR: 0.28, 95% CI: 0.12-0.66, p for interaction=0.01). CONCLUSIONS: Manual TA during primary PCI was not associated with improved clinical outcome at 12 months. The impact of TA may become clinically relevant with longer total ischemic time, forming a U-shaped relationship. PMID- 26867779 TI - Usefulness of anaerobic threshold to peak oxygen uptake ratio to determine the severity and pathophysiological condition of chronic heart failure. AB - BACKGROUND: Anaerobic threshold (AT) and peak oxygen uptake (VO2) are well known as indicators of severity and prognosis of heart failure. Since these parameters are regulated by many factors, multiple organ dysfunction may occur in chronic heart failure, and these two parameters would vary among patients. However, it is not clear whether AT and peak VO2 deteriorate similarly. Therefore, we planned to compare the degree of deterioration of these two parameters using a ratio of AT and peak VO2 (%AT/peak), and evaluated its significance in heart failure subjects. METHODS: One hundred ninety-four stable heart failure patients who had optimal medical treatment for at least 3 months were enrolled. Cardiopulmonary exercise testing, echocardiography, and blood sampling were examined within one week. Since %AT/peak varied from 50.3% to 108.5%, we divided patients into tertiles of %AT/peak [Group A, 50.1-70.0 (n=112), Group B, 70.1-90.0 (n=64), Group C, 90.1-110.0 (n=18)], and compared factors relating with skeletal muscle and heart failure among these 3 groups. RESULTS: In Group A, ratio of measured AT against predicted value (%AT) and measured peak VO2 against predicted value (%peak VO2) were similar (80.3+/-19.0% and 80.4+/-17.1%, respectively). Peak VO2 became lower as %AT/peak increased (Group B; 65.6+/-14.8%, p<0.01 vs. Group A, Group C; 38.3+/-9.7%, p<0.01 vs. Group B). On the other hand, %AT in Group B (77.1+/-18.5%) was similar to Group A, and diminished in Group C (58.0+/-8.2%, p<0.05 vs. Group B). Peak work rate and lean body mass were smaller in Group B than those in Group A. Although, left ventricular ejection fraction and E/E' deteriorated in Group B compared with Group A, plasma B-type natriuretic peptide and estimated glomerular filtration rate stayed constant in Group B and deteriorated in Group C. CONCLUSIONS: %AT/peak showed negative correlation with peak VO2. In chronic heart failure, muscle weakness occurs at an early stage, and this can be evaluated using %AT/peak. PMID- 26867780 TI - A reduced-order model-based study on the effect of intermittent pneumatic compression of limbs on the cardiovascular system. AB - This work investigates the effect that the application of intermittent pneumatic compression to lower limbs has on the cardiovascular system. Intermittent pneumatic compression can be applied to subjects with reduced or null mobility and can be useful for therapeutic purposes in sports recovery, deep vein thrombosis prevention and lymphedema drainage. However, intermittent pneumatic compression performance and the effectiveness are often difficult to predict. This study presents a reduced-order numerical model of the interaction between the cardiovascular system and the intermittent pneumatic compression device. The effect that different intermittent pneumatic compression operating conditions have on the overall circulation is investigated. Our findings confirm (1) that an overall positive effect on hemodynamics can be obtained by properly applying the intermittent pneumatic compression device and (2) that using intermittent pneumatic compression for cardiocirculatory recovery is feasible in subjects affected by lower limb disease. PMID- 26867781 TI - Establishing the biomechanical properties of the pelvic soft tissues through an inverse finite element analysis using magnetic resonance imaging. AB - The mechanical characteristics of the female pelvic floor are relevant when explaining pelvic dysfunction. The decreased elasticity of the tissue often causes inability to maintain urethral position, also leading to vaginal and rectal descend when coughing or defecating as a response to an increase in the internal abdominal pressure. These conditions can be associated with changes in the mechanical properties of the supportive structures-namely, the pelvic floor muscles-including impairment. In this work, we used an inverse finite element analysis to calculate the material constants for the passive mechanical behavior of the pelvic floor muscles. The numerical model of the pelvic floor muscles and bones was built from magnetic resonance axial images acquired at rest. Muscle deformation, simulating the Valsalva maneuver with a pressure of 4 KPa, was compared with the muscle displacement obtained through additional dynamic magnetic resonance imaging. The difference in displacement was of 0.15 mm in the antero-posterior direction and 3.69 mm in the supero-inferior direction, equating to a percentage error of 7.0% and 16.9%, respectively. We obtained the shortest difference in the displacements using an iterative process that reached the material constants for the Mooney-Rivlin constitutive model (c10=11.8 KPa and c20=5.53 E-02 KPa). For each iteration, the orthogonal distance between each node from the group of nodes which defined the puborectal muscle in the numerical model versus dynamic magnetic resonance imaging was computed. With the methodology used in this work, it was possible to obtain in vivo biomechanical properties of the pelvic floor muscles for a specific subject using input information acquired non-invasively. PMID- 26867782 TI - Comment to Comment article "Posterior component separation with transversus abdominis release successfully addresses recurrent ventral hernias following anterior component separation" Pauli EM, et al. Hernia 2015; 19: 285-291. Tulloh B, de Beaux AC and to Reply to comment article "Posterior component separation with transversus abdominis release successfully addresses recurrent ventral hernias following anterior component separation" Tulloh B et al. Hernia 2015; 19:687-688. Pauli EM, Rosen MJ. PMID- 26867783 TI - Plasma cells in primary melanoma. Prognostic significance and possible role of IgA. AB - Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (P<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (P=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism. PMID- 26867784 TI - Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians. AB - Large case series of renal amyloidosis subtypes have recently been published in the United States and Europe showing AL amyloidosis to be the predominant subtype in this part of the world. However, the most common subtypes of renal amyloidosis throughout the rest of the world are unknown. We present here the first large case series detailing the subtypes of renal amyloidosis among Egyptians. In this population, AA amyloidosis was the most common type of amyloidosis on renal biopsy at 48%. The newly described leukocyte chemotactic factor 2 amyloidosis (ALECT2) was the second most common type and represented nearly one-third of renal amyloid cases at 31%. AL accounted for only 20% of cases. The pathologic findings in ALECT2 cases were similar to those previously described in other case series. Thus ALECT2, which was initially thought to affect mainly Hispanics in the United States, appears to represent an important and likely underrecognized etiology of chronic kidney disease among Egyptians and probably in other ethnic groups around the world. PMID- 26867785 TI - Suicidality and its relationships with individual, family, peer, and psychopathology factors among adolescents with attention-deficit/hyperactivity disorder. AB - The aim of this study was to examine the prevalence rates of suicidal intent and its correlates among adolescents diagnosed with ADHD in Taiwan. A total of 287 adolescents aged 11-18 years and diagnosed with ADHD participated in this study. Their suicidal ideation and suicide attempts were assessed. Logistic regression analysis was used to examine the associations of suicide with individual, family, peer, ADHD, and psychopathology factors. A total of 12.2% of the participants reported suicidal ideation or a suicide attempt. A logistic regression analysis model showed that adolescents who were older, were bullying perpetrators, and reported high depression level were more likely to have suicidal intent. These three factors were also significantly correlated with suicidal ideation; however, only having high depression level was significantly correlated with suicidal attempts. The results of this study showed that a high proportion of adolescents with ADHD reported suicidal ideation or a suicide attempt. Multiple factors were significantly associated with suicidal intent among adolescents with ADHD. Clinicians, educational professionals, and parents of adolescents with ADHD should monitor the possibility of suicide in adolescents with ADHD who exhibit the correlates of suicidal intent identified in this study. PMID- 26867786 TI - Multisensory body representation in autoimmune diseases. AB - Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system's functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist. PMID- 26867789 TI - Immunolocalization of AMPA receptor subunits within the enteric nervous system of the mouse colon and the effect of their activation on spontaneous colonic contractions. AB - BACKGROUND: The appropriate expression of specific neurotransmitter receptors within the cellular networks that compose the enteric nervous system (ENS) is central to the regulation of gastrointestinal (GI) functions. While the ENS expression patterns of the neurotransmitter glutamate have been well documented, the localization of its receptors on ENS neurons remains to be fully characterized. We investigated the expression patterns of glutamate receptor AMPA subunits within ENS neurons of the mouse colon and the consequences of their pharmacological activation on spontaneous colonic contractility. METHODS: RT-PCR was used to detect individual AMPA receptor (GluR 1-4) subunit expression at the mRNA level in mouse colon tissue. Immunohistochemistry and confocal microscopy was used to localize the expression of the GluR1 and 4 subunits in colon tissue. Brain tissue was used as a positive control. Organ bath preparations were used to determine the effect of AMPA receptors activation on the force and frequency of colonic longitudinal smooth muscle spontaneous contractions. KEY RESULTS: GluR1, 3, 4 mRNA was detected in the mouse colon. Immunoreactivity for GluR1 and 4 subunits was detected on the somatic and dendritic surfaces of subpopulations of neurochemically defined ENS neurons. The pharmacological activation of AMPA receptors increased the force but not frequency of spontaneous colonic contractions. CONCLUSIONS & INFERENCES: Molecularly distinct AMPA receptor subtypes are differentially expressed within the neural networks of the mouse colon and have a direct role in motility. These data provide the rationale for the development of AMPA-selective ligands for the therapeutic delivery to the GIT in motility disorders. PMID- 26867788 TI - Age and muscle strength mediate the age-related biomechanical plasticity of gait. AB - PURPOSE: Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait. METHODS: Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years) participated in biomechanical gait analyses at 1.5 m/s and were also measured for maximal leg strength. RESULTS: Analysis 1 confirmed previous data as old compared with young adults walked with 50 % more hip positive work and 18 % less ankle positive work. Analysis 2 showed that leg strength did not affect gait kinetics in groups of subjects with similar ages. In a weak young and a strong old group, Analysis 3 showed that old adults still walked with 23 % greater hip positive work. The group by joint interaction in Analysis 4 was suggestive of an even greater reliance on hip and less reliance on ankle work in weak compared with strong old adults. CONCLUSIONS: Age and leg strength both contribute to the age related changes in mechanical output during gait. Exercise prescription, normally targeting the knee extensors, should also involve ankle and hip muscles. PMID- 26867787 TI - Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair. AB - Research over the past decade on the cell-biomaterial interface has shifted to the third dimension. Besides mimicking the native extracellular environment by 3D cell culture, hydrogels offer the possibility to generate well-defined 3D biofabricated tissue analogs. In this context, gelatin-methacryloyl (gelMA) hydrogels have recently gained increased attention. This interest is sparked by the combination of the inherent bioactivity of gelatin and the physicochemical tailorability of photo-crosslinkable hydrogels. GelMA is a versatile matrix that can be used to engineer tissue analogs ranging from vasculature to cartilage and bone. Convergence of biological and biofabrication approaches is necessary to progress from merely proving cell functionality or construct shape fidelity towards regenerating tissues. GelMA has a critical pioneering role in this process and could be used to accelerate the development of clinically relevant applications. PMID- 26867791 TI - Differential characteristics of photochemical acclimation to cold in two contrasting sweet sorghum hybrids. AB - Sweet sorghum has a photosynthetic system which is highly sensitive to cold stress and hence strongly limits its development in temperate environments; therefore, the identification of key exploitable cold tolerance traits is imperative. From a preliminary field trial, two dissimilar sweet sorghum hybrids (ICSSH31 and Bulldozer), in terms of early vigor and productivity, were selected for a controlled-environment trial aiming at identifying useful traits related to acclimation mechanisms to cold stress. The higher cold tolerance of Bulldozer was partially related to a more efficient photochemical regulation mechanism of the incoming light energy: the higher tolerance of photosystem II (PSII) to photo inactivation was because of a more effective dissipation capacity of the excess of energy and to a more balanced diversion of the absorbed energy into alternative energy sinks. ICSSH31 increased the dissipation and accumulation of a large amount of xanthophylls, as in Bulldozer, but, at the same time, inactivated the oxygen evolving complex and the re-synthesis of chlorophyll (Chl) a and b, thus, leading to an overproduction of CO2 fixation enzymes after re-warming. In summary, in Bulldozer, the acclimation adjustments of the photosynthetic apparatus occurred through an efficient control of energy transfer toward the reaction centers, and this likely allowed a more successful seedling establishment; ICSSH31, conversely, exhibited a fast re-synthesis of Chl pigments, which appears to divert photosynthates from dry matter accumulation. Such broad acclimation traits may constitute a source for selecting higher genetic gain traits relevant for enlarging the growing season of promising biomass sorghum ideotypes in temperate climates. PMID- 26867790 TI - Anthropogenic effects are associated with a lower persistence of marine food webs. AB - Marine coastal ecosystems are among the most exposed to global environmental change, with reported effects on species biomass, species richness and length of trophic chains. By combining a biologically informed food-web model with information on anthropogenic influences in 701 sites across the Caribbean region, we show that fishing effort, human density and thermal stress anomaly are associated with a decrease in local food-web persistence. The conservation status of the site, in turn, is associated with an increase in food-web persistence. Some of these associations are explained through effects on food-web structure and total community biomass. Our results unveil a hidden footprint of human activities. Even when food webs may seem healthy in terms of the presence and abundance of their constituent species, they may be losing the capacity to withstand further environmental degradation. PMID- 26867792 TI - Varicella zoster virus antibody detection: A comparison of four commonly used techniques. AB - BACKGROUND: Antibody tests for the varicella zoster virus (VZV) include neutralization, fluorescent antibody to membrane antigen (FAMA), immune adherence hemagglutination (IAHA), enzyme immunoassay (EIA), glycoprotein-based enzyme linked immunosorbent assay (gpELISA), and complement fixation (CF) tests. Of these, FAMA is considered the most sensitive. However, in Japan, the EIA method is most frequently employed. OBJECTIVE: The VZV antibody detection rate of the FAMA, EIA, gpELISA, and IAHA methods was compared. METHODS: Four types of antibody tests were conducted with sera collected from 83 college students. The relationships between two antibody tests were examined using Pearson's correlation coefficients. RESULTS: All 83 subjects were observed to be VZV antibody-positive using the FAMA method. The Pearson correlation coefficients of gpELISA, EIA, and IAHA relative to FAMA were 0.808, 0.782, and 0.356, respectively. The positive agreement rate of IAHA relative to FAMA was 88.0% (73/83), whereas those of gpELISA and EIA were both 97.6% (81/83). Furthermore, EIA showed 100% positive agreement with gpELISA and a high correlation coefficient of 0.911, whereas these values for IAHA compared to gpELISA were much lower (90.1% and 0.530). The calculated Pearson correlation coefficient for comparison of the EIA and IAHA methods was 0.498, with a positive agreement rate of 90.1% (73/81). CONCLUSIONS: The EIA method should be employed in Japan based on the similarity of the positivity between EIA and gpELISA, as it is more available and practical than gpELISA. PMID- 26867793 TI - The efficacy and safety of cefepime or meropenem in the treatment of febrile neutropenia in patients with lung cancer. A randomized phase II study. AB - Febrile neutropenia frequently develops after chemotherapy. There is little evidence to indicate the type of antimicrobial agents that should be used in the treatment of febrile neutropenia in patients with solid tumors. The objective is to determine the efficacy and safety of cefepime (CFPM) and meropenem (MEPM) in the treatment of febrile neutropenia in lung cancer patients in a prospective randomized study. FN patients with lung cancer were randomly divided into CFPM or MEPM groups. The primary end-point was the response rate. The secondary end points were the defervescence rates at 72 h, 7 days, 14 days and the incidence of adverse events. Twenty-one patients were treated with CFPM and 24 patients were treated with MEPM. One patient died of FN. The CFPM treatment completion rate was 17.65% (95% CI; 0.00-35.77%), while the MEPM treatment completion rate was 38.10% (95% CI; 17.33-58.87%). The defervescence rates at 72 h, 7 days, and 14 days were 70.59%, 86.67%, and 100.00%, respectively in the CFPM group; and 65.00%, 84.21%, and 92.31% in the MEPM group. Adverse events were observed in 33.33% of the CFPM group and 45.83% of the MEPM group. The response rate of the CFPM group was 94.12% (95% CI; 73.02-98.95%), while that of the MEPM group was 85.71% (95% CI; 65.36-95.02%). No differences were found in the efficacy or safety of CFPM and MEPM in the treatment of febrile neutropenia in patients with lung cancer. PMID- 26867794 TI - A case of miriplatin-induced lung injury. AB - A 69-year-old man with an 8-year history of hepatocellular carcinoma (HCC) was hospitalized for treatment of recurrent tumour. In 2010, the first transcatheter arterial chemoembolization (TACE) using miriplatin with agents (Lipiodol Ultra Fluid) was performed and did not occur any adverse events. In 2014, since his HCC recurred, the TACE using miriplatin with agents was performed. Following this therapy, pyrexia occurred on day 3, followed by respiratory failure with cough and dyspnea on day 5. Chest radiography revealed scattered infiltration in the right upper lung fields, and chest computed tomography revealed ground grass attenuations, indicating fibrotic non-specific interstitial pneumonia. These findings progressively deteriorated, and a diagnosis of miriplatin-induced lung injury was made. His respiratory failure also progressively deteriorated. Treatment with pulse methylprednisolone therapy resulted in a dramatic improvement in both patient symptoms and radiological abnormalities. PMID- 26867795 TI - Antimycobacterial activity of methanolic plant extract of Artemisia capillaris containing ursolic acid and hydroquinone against Mycobacterium tuberculosis. AB - OBJECTIVE: In order to protect against Mycobacterium tuberculosis (MTB) infection, novel drugs and new targets should be screened from the vast source of plants. We investigated the potentiality of the herbal plant of Artemisia capillaris extract (AC) against Mycobacterium tuberculosis. DESIGN: In this study, we isolated ursolic acid and hydroquinone by bio-activity guided fractionation from the methanol extracts of AC, and tested the inhibitory effects against several strains of MTB. Anti-mycobacterial evaluation of these compounds was carried out using the MGITTM 960 and resazurin assay. Mycobacterial morphological changes due to the treatment of these compounds were further evaluated by Transmission electron microscopy (TEM). RESULTS: Ursolic acid (UA) and hydroquinone (HQ) inhibited the growth of both susceptible and resistant strains of M. tuberculosis. The MIC (minimum inhibitory concentration) values of both UA and HQ were 12.5 MUg/ml against the susceptible strains of M. tuberculosis. Also both UA and HQ showed 12.5-25 MUg/ml of MIC values against MDR/XDR MTB strains. However, against clinical strains of MTB, UA was found sensitive against those strains that are sensitive against both INH and RFP but resistant against those strains that are resistant to INH. On the other hand HQ was sensitive against all clinical strains. TEM image-analysis of the strain H37Ra after treatment with UA revealed cell wall lysis, whereas HQ-treated cells showed deformed cytoplasmic morphology. CONCLUSION: All these results indicate that AC extracts containing UA and HQ possess promising chemotherapeutic potency against MTB for future use. PMID- 26867796 TI - Protective effects of intravenous immunoglobulin and antimicrobial agents on acute pneumonia in leukopenic mice. AB - Multi-drug resistant Pseudomonas aeruginosa causes the type of acute lung injury that is strongly associated with bacteremia, sepsis, and mortality, especially under immunocompromised conditions. Although administration of immunoglobulin solution is an applicable immunotherapy in immunocompromised patients, efficacy of immunoglobulin administration against multi-drug resistant P. aeruginosa pneumonia has not been well evaluated. In this study, we investigated the effectiveness of prophylactic administration of immunoglobulin solution (IVIG) in comparison with that of other types of antimicrobial agents, such as anti-PcrV IgG, piperacillin/tazobactam, or colistin in an immunocompromised mouse model of P. aeruginosa pneumonia. Colistin was the most effective agent for preventing acute lung injury, bacteremia, cytokinemia, and sepsis. Among the four tested antimicrobial agents, after colistin, anti-PcrV IgG and IVIG were the most effective at protecting mice from mortality. Piperacillin/tazobactam did not prevent acute lung injury or bacteremia; rather, it worsened lung histology. The data suggest that using an agent for which a positive result in an in vitro susceptibility test has been obtained may not always prevent acute lung injury in a leukopenic host infected with P. aeruginosa. Clinicians should consider the possibility of discrepancies between in vitro and in vivo tests because the absence of in vitro bactericidal activity in an antimicrobial agent is not always a reliable predictor of its lack of ability to eradicate bacteria in vivo, even in immunocompromised hosts. Based on our findings, the potential protective effects of IVIG against the acute lung injury induced by P. aeruginosa should be reevaluated. PMID- 26867797 TI - Client perspective assessment of women's satisfaction towards labour and delivery care service in public health facilities at Arba Minch town and the surrounding district, Gamo Gofa zone, south Ethiopia. AB - BACKGROUND: A woman's satisfaction with labour and delivery care service has a good effect on her health and subsequent utilization of the services. Thus knowledge about women's satisfaction on labour and delivery care used to enhances the services utilization. The objective of this study was to assess the satisfaction of women's towards labour and delivery care service and identify factors associated it at public health facilities in Arba Minch town and the surrounding district, Gamo Gofa zone, southern Ethiopia. METHODS: Facility based cross sectional study was conducted among women who gave birth at public health facility. A total 256 women who gave birth during the study period were included in the study. Data was collected using a structured questionnaire. Satisfaction level was measured using a 5 point-Likert scale questions. Data were entered using Epi data version 3.5.1 and analyzed using SPSS 20.0 statistical software. Factor analysis was employed for Likert scale questions to extract factor represented each of the scale which facilitate treatment of variable as continuous for further analysis. Bi-variate and multivariable logistic regression analysis was employed to identify association between women's satisfaction and predicator variables. Statistical significance was declared at P value <0.05 on final model. The strength of association was interpreted using the adjusted odds ratio and 95% CI. RESULT: This study revealed that 90.2% of women who gave birth in public health facilities were satisfied with labour and delivery care. Factors associated with women's satisfaction with labour and delivery care services include: not attending formal education [AOR = 8.00, 95% CI = (1.52, 12.27)] attending antenatal care four times and more [AOR = 5.00, 95% CI = (1.76, 14.20)] waiting below 15 minutes to be seen by health professional [AOR = 3.37, 95% CI = (1.14, 9.97)] and not paying for drugs and supplies [AOR = 6.19, 95% CI = (1.34, 18.59)]. CONCLUSION: Although majority of women were satisfied with the labour and delivery service they got, their level of satisfaction was influenced by educational status, number of ANC visits, waiting time, and payment for drug and supplies. Thus, public health intervention working on improving delivery care should consider these factors. PMID- 26867798 TI - The palaeobiology of high latitude birds from the early Eocene greenhouse of Ellesmere Island, Arctic Canada. AB - Fossils attributable to the extinct waterfowl clade Presbyornithidae and the large flightless Gastornithidae from the early Eocene (~52-53 Ma) of Ellesmere Island, in northernmost Canada are the oldest Cenozoic avian fossils from the Arctic. Except for its slightly larger size, the Arctic presbyornithid humerus is not distinguishable from fossils of Presbyornis pervetus from the western United States, and the Gastornis phalanx is within the known size range of mid-latitude individuals. The occurrence of Presbyornis above the Arctic Circle in the Eocene could be the result of annual migration like that of its living duck and geese relatives, or it may have been a year-round resident similar to some Eocene mammals on Ellesmere and some extant species of sea ducks. Gastornis, along with some of the mammalian and reptilian members of the Eocene Arctic fauna, likely over-wintered in the Arctic. Despite the milder (above freezing) Eocene climate on Ellesmere Island, prolonged periods of darkness occurred during the winter. Presence of these extinct birds at both mid and high latitudes on the northern continents provides evidence that future increases in climatic warming (closer to Eocene levels) could lead to the establishment of new migratory or resident populations within the Arctic Circle. PMID- 26867800 TI - Optical detection of radon decay in air. AB - An optical radon detection method is presented. Radon decay is directly measured by observing the secondary radiolumines cence light that alpha particles excite in air, and the selectivity of coincident photon detection is further enhanced with online pulse-shape analysis. The sensitivity of a demonstration device was 6.5 cps/Bq/l and the minimum detectable concentration was 12 Bq/m(3) with a 1 h integration time. The presented technique paves the way for optical approaches in rapid radon detec tion, and it can be applied beyond radon to the analysis of any alpha-active sample which can be placed in the measurement chamber. PMID- 26867799 TI - beta-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1. AB - beta-elemene, a Curcuma wenyujin plant extract, has been used widely as a tumor adjuvant therapeutic agent. However, how to obtain optimum therapeutic effects by combining this compound with other agents remain unclear. In this study, we found that beta-elemene, which alone had little effect on hepatocellular carcinoma (HCC) cell proliferation, exerted a synergistic anti-proliferative effect in HCC cells when dosed in combination with oxaliplatin, which increased the amounts of platinum accumulation and platinum-DNA adduct significantly and augmented the oxaliplatin-induced apoptosis. Western blot and laser scanning confocal microscopy studies indicated that beta-elemene enhanced the sensitivity of HCC cells to oxaliplatin by upregulating copper transporter 1 (CTR1), a major controller of intracellular platinum accumulation. In an orthotopic transplantation HCC model in nude mice, HCC tumor growth was inhibited significantly by oxaliplatin combined with beta-elemene, as compared with oxaliplatin alone. Notably, CTR1 protein expression in xenograft HCC was upregulated in mice who received beta-elemene treatment. Taken together, our findings show that beta-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of beta-elemene and oxaliplatin deserve further evaluation in clinical settings. PMID- 26867801 TI - Curcumin: A Natural Multitarget Treatment for Pancreatic Cancer. PMID- 26867803 TI - On spatial pattern of concentration distribution for Taylor dispersion process. AB - Taylor dispersion is a key concept in many fields. In the present paper, we characterize the pattern of the complete spatial concentration distribution for laminar tube flow; the obtained simple description is shown to represent the nature of Taylor dispersion. Importantly, we find that during the approach to the longitudinal normality of the transverse mean concentration at the time scale of R(2)/D (R is the tube radius and D is the molecular diffusivity), the solute concentration becomes uniformly distributed across a family of invariant curved transverse surfaces instead of the flat cross-sections in the traditional view. The family of curved surfaces is analytically determined, and a transformation is devised for the previously obtained analytical solution to discuss the decay of the concentration difference across the curved surfaces. The approach to a uniform concentration across the flat cross-sections to the same degree (~3% by concentration difference percentage), achieved at a time-scale of 100 R(2)/D, is shown to be the natural consequence of the longitudinal separation of the concentration contours on the curved surfaces. PMID- 26867802 TI - Examining Mediators and Moderators of Yoga for Women With Breast Cancer Undergoing Radiotherapy. AB - Hypothesis This study examines moderators and mediators of a yoga intervention targeting quality-of-life (QOL) outcomes in women with breast cancer receiving radiotherapy.Methods Women undergoing 6 weeks of radiotherapy were randomized to a yoga (YG; n = 53) or stretching (ST; n = 56) intervention or a waitlist control group (WL; n = 54). Depressive symptoms and sleep disturbances were measured at baseline. Mediator (posttraumatic stress symptoms, benefit finding, and cortisol slope) and outcome (36-item Short Form [SF]-36 mental and physical component scales [MCS and PCS]) variables were assessed at baseline, end-of-treatment, and 1-, 3-, and 6-months posttreatment. Results Baseline depressive symptoms (P = .03) and sleep disturbances (P < .01) moderated the Group * Time effect on MCS, but not PCS. Women with high baseline depressive symptoms in YG reported marginally higher 3-month MCS than their counterparts in WL (P = .11). Women with high baseline sleep disturbances in YG reported higher 3-months MCS than their counterparts in WL (P < .01) and higher 6-month MCS than their counterparts in ST (P = .01). YG led to greater benefit finding than ST and WL across the follow-up (P = .01). Three-month benefit finding partially mediated the effect of YG on 6 month PCS. Posttraumatic stress symptoms and cortisol slope did not mediate treatment effect on QOL. Conclusion Yoga may provide the greatest mental-health related QOL benefits for those experiencing pre-radiotherapy sleep disturbance and depressive symptoms. Yoga may improve physical-health-related QOL by increasing ability to find benefit in the cancer experience. PMID- 26867807 TI - Accuracy of secondary maxillofacial reconstruction with prefabricated fibula grafts using 3D planning and guided reconstruction. AB - BACKGROUND: We compared the pre-operative 3D-surgical plan with the surgical outcome of complex two-stage secondary reconstruction of maxillofacial defects using inserted implants in the prefabricated fibula graft. METHODS: Eleven reconstructions of maxillofacial defects with prefabricated fibulas were performed using a 3D virtual planning. Accuracy of placement of the fibula grafts and dental implants was compared to pre-operative 3D virtual plans by superimposing pre-operative and post-operative CT-scans: we first superimposed the CT-scans on the antagonist jaw, to represent the outcome of occlusion, and then superimposed on the planned fibula segments. RESULTS: Superimposing the CT scans on the antagonist jaws revealed a median deviation of the fibula segments and implants of 4.7 mm (IQR:3-6.5 mm) and 5.5 mm (IQR:2.8-7 mm) from the planned position, respectively. Superimposing of the CT scans on the fibula segments revealed a median difference of fibula and implant placement of 0.3 mm (IQR:0-1.6 mm) and 2.2 mm (IQR:1.5-2.9 mm), respectively. CONCLUSIONS: The final position of the fibula graft is determined by the occlusion of the denture, which is designed from the 3D plan. From a prosthodontic perspective, the accuracy of 3D-surgical planning of reconstruction of maxillofacial defects with a fibula graft and the implants allows for a favorable functional position of the implants and fibula graft. PMID- 26867804 TI - Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity. AB - The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP-associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin-3). The effects of nutlin-3 on CDP osteotoxicity were studied using both pre- and post-operative treatment models. In both cases the addition of nutlin-3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01-0.001). In addition the combination of nutlin-3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri-operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1716-1724, 2016. PMID- 26867805 TI - Clinically relevant weakness in diverse populations of older adults participating in the International Mobility in Aging Study. AB - The aims of this study were to compare cut points for weakness proposed by Foundation for the National Institutes of Health (FNIH) Sarcopenia Project with cut points estimated with our own data; to assess the prevalence of clinically relevant handgrip strength (HGS) weakness according to published criteria across distinct populations of older adults; to estimate the ability of HGS weakness to identify slowness. This is a cross-sectional analysis of International Mobility in Aging Study (IMIAS) involving 1935 community-dwelling older adults, between 65 and 74 years, who completed HGS and gait speed assessment. We used baseline data from Tirana (Albania), Natal (Brazil), Manizales (Colombia), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). Weakness was defined according to sex-specific HGS cut points associated with slowness proposed by FNIH Sarcopenia Project. Slowness was defined as gait speed <0.8 m/s. IMIAS cut points for clinical weakness had good agreement with those proposed by FNIH. Weakness prevalence across the research sites ranged from 1.1 % (Saint-Hyacinthe) to 19.2 % (Manizales) among men. Women from Manizales (13.5 %) and Natal (19.3 %) had higher prevalence of weakness than their counterparts. FNIH cut points had a strong association with slowness, for both sexes. The IMIAS population generated cut points which were close to those proposed by FNIH. There was large variability in prevalence of weakness across our research sites. The HGS cut points for weakness proposed by FNIH performed well in IMIAS populations, providing a useful tool for screening older adults at risk for functional problems. PMID- 26867808 TI - Dibenzofurans and derivatives from lichens and ascomycetes. AB - Covering: up to 2016.When looking for dibenzofuran in the biochemical databases, most papers and reviews deal with pollutants and polychlorinated dibenzofurans like dioxins. But dibenzofurans are also biosynthetized by a wide diversity of organisms in nature. Even if dibenzofurans from natural sources represent a small class of secondary metabolites, compared to flavonoids, xanthones or terpenoids, they are often endowed with interesting biological properties which have been recently described. This review provides an update on papers describing dibenzofurans from lichens, ascomycetes and cultured mycobionts. Other sources, such as basidiomycetes, myxomycetes or plants produce sporadically interesting dibenzofurans in terms of structures and activities. PMID- 26867806 TI - Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli. AB - Cellular senescence is a multifactorial phenomenon of growth arrest and distorted function, which has been recognized as an important feature during tumor suppression mechanisms and a contributor to aging. Senescent cells have an altered secretion pattern called Senescence-Associated Secretory Phenotype (SASP) that comprises a complex mix of factors including cytokines, growth factors, chemokines, and matrix metalloproteinases. SASP has been related with local inflammation that leads to cellular transformation and neurodegenerative diseases. Various pathways for senescence induction have been proposed; the most studied is replicative senescence due to telomere attrition called replicative senescence (RS). However, senescence can be prematurely achieved when cells are exposed to diverse stimuli such as oxidative stress (stress-induced premature senescence, SIPS) or proteasome inhibition (proteasome inhibition-induced premature senescence, PIIPS). SASP has been characterized in RS and SIPS but not in PIIPS. Hence, our aim was to determine SASP components in primary lung fibroblasts obtained from CD-1 mice induced to senescence by PIIPS and compare them to RS and SIPS. Our results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented. Variations in glutathione-redox balance were also observed in SIPS and RS, and not in PIIPS. All senescence types SASP displayed a pro-inflammatory profile and increased proliferation in L929 mice fibroblasts exposed to SASP. However, the behavior observed was not exactly the same, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes. PMID- 26867809 TI - Recent Strategies for Improving the Catalytic Activity of 2D TMD Nanosheets Toward the Hydrogen Evolution Reaction. AB - Two-dimensional (2D) transition-metal dichalcogenide (TMD) nanosheets have emerged as a fascinating new class of materials for catalysis. These nanosheets are active for several important catalysis reactions including hydrogen evolution from water. The rich chemistry of TMDs combined with numerous strategies that allow tuning of their electronic properties make these materials very attractive for understanding the fundamental principles of electro- and photocatalysis, as well as for developing highly efficient, renewable, and affordable catalysts for large-scale production of hydrogen. Recent developments are highlighted and important challenges in using TMDs as catalysts are also discussed. PMID- 26867810 TI - Anticancer activity and radiosensitization effect of methyleneisoxazolidin-5-ones in hepatocellular carcinoma HepG2 cells. AB - Parthenolide (PTL), a well-known sesquiterpene lactone of natural origin with alpha,beta-unsaturated carbonyl structure, has proven to show promising anti cancer properties. In this report, anti-proliferative potential of two synthetic methyleneisoxazolidin-5-ones, MZ-6 and MZ-14, with the same structural motif, has been investigated in human hepatoma HepG2 cells. The effects on apoptosis induction and DNA damage were evaluated. All compounds decreased the number of live cells and increased the number of late apoptotic cells. However, only MZ-14 was able to induce DNA damage. Both synthetic compounds increased intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential changes at the same level as PTL. Additionally, cell survival was analyzed after a combined treatment, in which HepG2 cells were preincubated for 24 h with MZ-6, MZ-14 or PTL and irradiated with different doses of X-rays. The inhibition of cell survival was assessed by the clonogenic assay. We have shown that the clone formation was strongly inhibited by the combined treatment. The synergistic effect was observed for all three compounds but MZ-6 was significantly more effective. It is interesting to note that in HepG2 cells MZ-6 was the least cytotoxic of the tested compounds, did not induce DNA damage and was less active than the others in the clonogenic cell survival assay. It seems advantages from the point of view of the further in vivo studies that the compound with the lowest cytotoxic activity showed the strongest sensitizing effect. PMID- 26867812 TI - HLA-DRB1, -DQA1 and -DQB1 genotyping of 180 Czech individuals from the Czech Republic pop 3. AB - One hundred and eighty Czech individuals from the Czech Republic pop 3 were genotyped at the HLA-DRB1, -DQA1 and -DQB1 loci using sequence-specific primers PCR methods. HLA-DRB1, -DQA1 and -DQB1 genotypes are consistent with expected Hardy-Weinberg (HW) proportions. These genotype data are available in the Allele Frequencies Net Database under identifier AFND. PMID- 26867811 TI - Long-Lasting Sound-Evoked Afterdischarge in the Auditory Midbrain. AB - Different forms of plasticity are known to play a critical role in the processing of information about sound. Here, we report a novel neural plastic response in the inferior colliculus, an auditory center in the midbrain of the auditory pathway. A vigorous, long-lasting sound-evoked afterdischarge (LSA) is seen in a subpopulation of both glutamatergic and GABAergic neurons in the central nucleus of the inferior colliculus of normal hearing mice. These neurons were identified with single unit recordings and optogenetics in vivo. The LSA can continue for up to several minutes after the offset of the sound. LSA is induced by long-lasting, or repetitive short-duration, innocuous sounds. Neurons with LSA showed less adaptation than the neurons without LSA. The mechanisms that cause this neural behavior are unknown but may be a function of intrinsic mechanisms or the microcircuitry of the inferior colliculus. Since LSA produces long-lasting firing in the absence of sound, it may be relevant to temporary or chronic tinnitus or to some other aftereffect of long-duration sound. PMID- 26867813 TI - Current outcomes of chronic active antibody mediated rejection - A large single center retrospective review using the updated BANFF 2013 criteria. AB - BACKGROUND: The updated BANFF 2013 criteria has enabled a more standardized and complete serologic and histopathologic diagnosis of chronic active antibody mediated rejection (cAMR). Little data exists on the outcomes of cAMR since the initiation of this updated criteria. METHODS: 123 consecutive patients with biopsy proven cAMR (BANFF 2013) between 2006 and 2012 were identified. RESULTS: Patients identified with cAMR were followed for a median of 9.5 (2.7-20.3) years after transplant and 4.3 (0-8.8) years after cAMR. Ninety-four (76%) recipients lost their grafts with a median survival of 1.9 years after diagnosis with cAMR. Mean C4d and allograft glomerulopathy scores were 2.6 +/- 0.7 and 2.2 +/- 0.8, respectively. 53.2% had class II DSA, 32.2% had both class I and II, and 14.5% had class I DSA only. Chronicity score >8 (HR 2.9, 95% CI 1-8.4, p=0.05), DSA >2500 MFI (HR 2.8, 95% CI 1.1-6.8, p=0.03), Scr >3mg/dL (HR 3.2, 95% CI 1.6-6.3, p=0.001) and UPC >1g/g (HR 2.5, 95% CI 1.4-4.5, p=0.003) were associated with a higher risk of graft loss. CONCLUSIONS: cAMR was associated with poor graft survival after diagnosis. Improved therapies and earlier detection strategies are likely needed to improve outcomes of cAMR in kidney transplant recipients. PMID- 26867815 TI - Host switching of human lice to new world monkeys in South America. AB - The coevolution between a host and its obligate parasite is exemplified in the sucking lice that infest primates. In the context of close lice-host partnerships and cospeciation, Pediculus mjobergi, the louse of New World primates, has long been puzzling because its morphology resembles that of human lice. To investigate the possibility that P. mjobergi was transmitted to monkeys from the first humans who set foot on the American continent thousands of years ago, we obtained and compared P. mjobergi lice collected from howler monkeys from Argentina to human lice gathered from a remote and isolated village in Amazonia that has escaped globalization. Morphological examinations were first conducted and verified the similarity between the monkey and human lice. The molecular characterization of several nuclear and mitochondrial genetic markers in the two types of lice revealed that one of the P. mjobergi specimens had a unique haplotype that clustered with the haplotypes of Amazonian head lice that are prevalent in tropical regions in the Americas, a natural habitat of New World monkeys. Because this phylogenetic group forms a separate branch within the clade of lice from humans that were of American origin, this finding indicates that human lice have transferred to New World monkeys. PMID- 26867814 TI - Incremental Hemodialysis, Residual Kidney Function, and Mortality Risk in Incident Dialysis Patients: A Cohort Study. AB - BACKGROUND: Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient's residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. STUDY DESIGN: A longitudinal cohort. SETTING & PARTICIPANTS: 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. PREDICTOR: Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. OUTCOMES: Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. RESULTS: Among 23,645 included patients, 51% had substantial renal urea clearance (>=3.0mL/min/1.73m(2)) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (<=3.0mL/min/1.73m(2); HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600mL/d. LIMITATIONS: Potential selection bias and wide CIs. CONCLUSIONS: Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis. PMID- 26867816 TI - Comparative sequence analysis of domain I of Plasmodium falciparum apical membrane antigen 1 from Saudi Arabia and worldwide isolates. AB - The apical membrane antigen 1 of Plasmodium falciparum (PfAMA1) plays a crucial role in erythrocyte invasion and is a target of protective antibodies. Although domain I of PfAMA1 has been considered a promising vaccine component, extensive sequence diversity in this domain could compromise an effective vaccine design. To explore the extent of sequence diversity in domain I of PfAMA1, P. falciparum infected blood samples from Saudi Arabia collected between 2007 and 2009 were analyzed and compared with those from worldwide parasite populations. Forty-six haplotypes and a novel codon change (M190V) were found among Saudi Arabian isolates. The haplotype diversity (0.948+/-0.004) and nucleotide diversity (0.0191+/-0.0008) were comparable to those from African hyperendemic countries. Positive selection in domain I of PfAMA1 among Saudi Arabian parasite population was observed because nonsynonymous nucleotide substitutions per nonsynonymous site (dN) significantly exceeded synonymous nucleotide substitutions per synonymous site (dS) and Tajima's D and its related statistics significantly deviated from neutrality in the positive direction. Despite a relatively low prevalence of malaria in Saudi Arabia, a minimum of 17 recombination events occurred in domain I. Genetic differentiation was significant between P. falciparum in Saudi Arabia and parasites from other geographic origins. Several shared or closely related haplotypes were found among parasites from different geographic areas, suggesting that vaccine derived from multiple shared epitopes could be effective across endemic countries. PMID- 26867817 TI - Control of the rotary inverted pendulum through threshold-based communication. AB - This paper deals with the real implementation of an event-based control structure for the classical rotary inverted pendulum. The communication between controller and plant is performed through Ethernet (TCP/IP) which leads to a Networked Control System. The bandwidth used by the control loop is reduced, compared with the one that needs a conventional control, by using a threshold-based communication. The values of the thresholds have been determined by means of simulation techniques. The results over the real plant show how this technique can reach a significant reduction of the bandwidth consumed with a negligible worsening of the performance. PMID- 26867818 TI - Supporting the human life-raft in confronting the juggernaut of technology: Jens Rasmussen, 1961-1986. AB - Jens Rasmussen's contribution to the field of human factors and ergonomics has had a lasting impact. Six prominent interrelated themes can be extracted from his research between 1961 and 1986. These themes form the basis of an engineering epistemology which is best manifested by his abstraction hierarchy. Further, Rasmussen reformulated technical reliability using systems language to enable a proper human-machine fit. To understand the concept of human-machine fit, he included the operator as a central component in the system to enhance system safety. This change resulted in the application of a qualitative and categorical approach for human-machine interaction design. Finally, Rasmussen's insistence on a working philosophy of systems design as being a joint responsibility of operators and designers provided the basis for averting errors and ensuring safe and correct system functioning. PMID- 26867819 TI - Efficacy of 11 Brazilian essential oils on lethality of the cattle tick Rhipicephalus (Boophilus) microplus. AB - Herbal extracts have been investigated as an alternative for parasite control, aiming to slow the development of resistance and to obtain low-cost biodegradable parasiticides. The goal of this study was to evaluate the efficacy, in vitro, of 11 essential oils from Brazil on reproductive efficiency and lethality of the cattle tick Rhipicephalus (Boophilus) microplus. The effects of oils extracted from Curcuma longa, Zingiber officinale, Lippia alba, Lippia gracilis, Lippia origanoides, Lippia sidoides, Mentha arvensis, Mentha piperita, Croton cajucara (white and red), and Croton sacaquinha on ticks were investigated by the Immersion Test with Engorged Females (ITEF) and the modified Larval Packet Test (LPT). Distilled water and 2% Tween 80 were used as control treatments. Chemical analysis of the oils was done with gas chromatography coupled with mass spectrometry. Analysis of the in vitro tests using Probit (SAS program) allowed the calculation of lethal concentrations (LCs). Lower reproductive efficiency indexes and higher efficacy percentages in the ITEF were obtained with the oils extracted from C. longa (24 and 71%, respectively) and M. arvensis oils (27 and 73%, respectively). Lower LC50 was reached with C. longa (10.24 mg/mL), L. alba (10.78 mg/mL), M. arvensis (22.31 mg/mL), L. sidoides (27.67 mg/mL), and C. sacaquinha (29.88 mg/mL) oils. In the LPT, species from Zingiberaceae and Verbenaceae families caused 100% lethality at 25 mg/mL, except for L. sidoides. The most effective oils were from C. longa, L. gracilis, L. origanoides, L. alba, and Z. officinale. The LC50 and LC90 were, respectively: 0.54 and 1.80 mg/mL, 3.21 and 7.03 mg/mL, 3.10 and 8.44 mg/mL, 5.85 and 11.14 mg/mL, and 7.75 and 13.62 mg/mL. The efficacy was directly related to the major components in each essential oil, and the oils derived from Croton genus presented the worst performance, suggesting the absence of synergistic effect among its compounds. Since C. longa, containing 62% turmerone, was the one most efficient against ticks, this compound may be potentially used for tick control, but further research is needed, especially to assess toxicity of these compounds to the host. These new studies, together with the results presented here, may provide a strong rationale for designing pre-clinical and clinical studies with these agents. PMID- 26867820 TI - Combined Epiregulin and Amphiregulin Expression Levels as a Predictive Biomarker for Panitumumab Therapy Benefit or Lack of Benefit in Patients With RAS Wild-Type Advanced Colorectal Cancer. AB - Importance: RAS wild-type (wt) status is necessary but not sufficient for response to anti-epidermal growth factor receptor (EGFR) agents in advanced colorectal cancer (aCRC). RNA expression of EGFR ligands epiregulin (EREG) and amphiregulin (AREG) may correlate with EGFR-targeted therapy efficacy in aCRC, so may represent a much-needed additional predictive marker for these drugs. Objective: To examine a novel ligand model in a randomized clinical trial of panitumumab, irinotecan, and ciclosporin in colorectal cancer (PICCOLO) with with the a priori hypothesis that high tumor expression of either AREG or EREG would predict panitumumab therapy benefit in RAS-wt patients; and low expression, lack of efficacy. Design, Setting, and Participants: Prospectively planned retrospective biomarker study from the PICCOLO trial, which tested the addition of panitumumab to irinotecan therapy in patients with KRAS wt aCRC who experienced failure with prior fluoropyrimidine treatment. The analysis was conducted between 2012 and 2014. A predefined dichotomous model classified tumors as "high expressor" (either EREG or AREG in top tertile for messenger RNA level) or "low expressor" (neither EREG nor AREG in top tertile). Ligand expression was assessed as a prognostic and predictive biomarker. Expression of AREG/EREG and RAS and BRAF mutations were assessed in archival tumor tissue. Main Outcomes and Measures: Primary end point was progression-free survival (PFS); secondary end points were response rate and overall survival (OS). Results: Of the 696 PICCOLO trial patients in the irinotecan-vs-irinotecan with panitumumab randomization, 331 had sufficient tumor tissue available and measurement of ligand expression was successful in 323. High ligand expression was not prognostic for OS (hazard ratio [HR], 0.79 [95% CI, 0.58-1.09]; P = .15) or PFS (HR, 0.93 [95% CI, 0.68 1.27]; P = .64). The primary population had RAS wt aCRC (n = 220); for RAS wt patients with high ligand expression, median (interquartile range [IQR]) PFS was 8.3 [4.0-11.0] months (irinotecan with panitumumab) vs 4.4 [2.8-6.7] months (irinotecan alone); HR, 0.38 [95% CI, 0.24-0.61]; P < .001). In RAS wt patients with low ligand expression, median (IQR) PFS was 3.2 [2.7-8.1] months (irinotecan with panitumumab) vs 4.0 [2.7-7.5] months (irinotecan); HR, 0.93 [95% CI, 0.64 1.37]; P = .73; interaction test results were significant [P = .01]). Less marked effects were seen for response rate (interaction P = .17) and OS (interaction P = .11). Conclusions and Relevance: High ligand expression is a predictive marker for panitumumab therapy benefit on PFS in RAS wt patients; conversely, patients with low ligand expression gained no benefit. The current "opt-in" strategy for anti-EGFR therapy in all patients with RAS wt aCRC should be questioned. Expression of EREG/AREG is a useful biomarker for anti-EGFR therapy; optimization for clinical use is indicated. Trial Registration: isrctn Identifier: ISRCTN93248876. PMID- 26867821 TI - Anomalous magneto-elastic and charge doping effects in thallium-doped BaFe2As2. AB - Within the BaFe2As2 crystal lattice, we partially substitute thallium for barium and report the effects of interlayer coupling in Ba(1-x)Tl(x)Fe2As2 crystals. We demonstrate the unusual effects of magneto-elastic coupling and charge doping in this iron-arsenide material, whereby Neel temperature rises with small x, and then falls with additional x. Specifically, we find that Neel and structural transitions in BaFe2As2 (T(N) = T(s) = 133 K) increase for x = 0.05 (T(N) = 138 K, T(s) = 140 K) from magnetization, heat capacity, resistivity, and neutron diffraction measurements. Evidence from single crystal X-ray diffraction and first principles calculations attributes the stronger magnetism in x = 0.05 to magneto-elastic coupling related to the shorter intraplanar Fe-Fe bond distance. With further thallium substitution, the transition temperatures decrease for x = 0.09 (T(N) = T(s) = 131 K), and this is due to charge doping. We illustrate that small changes related to 3d transition-metal state can have profound effects on magnetism. PMID- 26867822 TI - Acupuncture in Pediatrics. AB - There has been extensive research on the use of acupuncture in adults with a wide array of conditions. Much less research has been conducted on the use of acupuncture in children. In this article, we review the history and philosophy of acupuncture, and the literature on its effectiveness and safety in children and adolescents, giving special attention to the pediatric and adolescent conditions that have been most studied in high-quality randomized controlled trials (RCTs). PMID- 26867823 TI - Commentary. PMID- 26867824 TI - Update of Antithrombotic Guidelines: Medical Professionalism and the Funnel of Knowledge. PMID- 26867825 TI - Physiologic Markers of Exercise as a Potential Screening Tool for the Detection of Pulmonary Hypertension: "alpha" Few Steps Forward. PMID- 26867826 TI - Disparities in Cystic Fibrosis Care and Outcome: Socioeconomic Status and Beyond. PMID- 26867827 TI - Atrial Fibrillation and Aging: Risky Mutual Relationships. PMID- 26867828 TI - POINT: Does Low-Dose Oxygen Expose Patients With COPD to More Radiation-Like Risks Than Patients Without COPD? Yes. PMID- 26867829 TI - COUNTERPOINT: Does Low-Dose Oxygen Expose Patients With COPD to More Radiation Like Risks Than Patients Without COPD? No. PMID- 26867830 TI - Rebuttal From Drs Kopp and Stavas. PMID- 26867831 TI - Rebuttal From Drs Christopher and Repine. PMID- 26867832 TI - Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. AB - BACKGROUND: We update recommendations on 12 topics that were in the 9th edition of these guidelines, and address 3 new topics. METHODS: We generate strong (Grade 1) and weak (Grade 2) recommendations based on high- (Grade A), moderate- (Grade B), and low- (Grade C) quality evidence. RESULTS: For VTE and no cancer, as long term anticoagulant therapy, we suggest dabigatran (Grade 2B), rivaroxaban (Grade 2B), apixaban (Grade 2B), or edoxaban (Grade 2B) over vitamin K antagonist (VKA) therapy, and suggest VKA therapy over low-molecular-weight heparin (LMWH; Grade 2C). For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). We have not changed recommendations for who should stop anticoagulation at 3 months or receive extended therapy. For VTE treated with anticoagulants, we recommend against an inferior vena cava filter (Grade 1B). For DVT, we suggest not using compression stockings routinely to prevent PTS (Grade 2B). For subsegmental pulmonary embolism and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C), and anticoagulation over clinical surveillance with a high risk (Grade 2C). We suggest thrombolytic therapy for pulmonary embolism with hypotension (Grade 2B), and systemic therapy over catheter-directed thrombolysis (Grade 2C). For recurrent VTE on a non-LMWH anticoagulant, we suggest LMWH (Grade 2C); for recurrent VTE on LMWH, we suggest increasing the LMWH dose (Grade 2C). CONCLUSIONS: Of 54 recommendations included in the 30 statements, 20 were strong and none was based on high-quality evidence, highlighting the need for further research. PMID- 26867833 TI - Validation of the International Medical Prevention Registry on Venous Thromboembolism Bleeding Risk Score. AB - BACKGROUND: Recent guidelines recommend assessing medical inpatients for bleeding risk prior to providing chemical prophylaxis for VTE. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding risk score (BRS) was derived from a well-defined population of medical inpatients but it has not been validated externally. We sought to externally validate the IMPROVE BRS. METHODS: We prospectively collected characteristics on admission and VTE prophylaxis data each hospital day for all patients admitted for a medical illness to the Walter Reed Army Medical Center over an 18-month period. We calculated the IMPROVE BRS for each patient using admission data and reviewed medical records to identify bleeding events. RESULTS: From September 2009 through March 2011, 1,668 inpatients met the IMPROVE inclusion criteria. Bleeding events occurred during 45 separate admissions (2.7%); 31 events (1.9%) were major and 14 (0.8%) were nonmajor but clinically relevant. Two hundred fifty-six patients (20.7%) had an IMPROVE BRS >= 7.0. Kaplan-Meier curves showed a higher cumulative incidence of major (P = .02) and clinically important (major plus clinically relevant nonmajor) (P = .06) bleeding within 14 days in patients with an IMPROVE BRS >= 7.0. An IMPROVE BRS >= 7.0 was associated with major bleeding in Cox regression analysis adjusted for administration of chemical prophylaxis (OR, 2.6; 95% CI, 1.1-5.9; P = .03); there was a trend toward a significant association with clinically important bleeding (OR, 1.9; 95% CI, 0.9-3.7; P = .07). CONCLUSIONS: The IMPROVE BRS calculated at admission predicts major bleeding in medical inpatients. This model may help assess the relative risks of bleeding and VTE before chemoprophylaxis is administered. PMID- 26867834 TI - Is Alveolar Macrophage Phagocytic Dysfunction in Children With Protracted Bacterial Bronchitis a Forerunner to Bronchiectasis? AB - BACKGROUND: Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation. METHODS: Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1beta was measured by enzyme-linked immunosorbent assay. RESULTS: For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P < .001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi; PBB and bronchiectasis, respectively); median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%); PBB, 16% (IQR, 11%-16%); control subjects, 19.0% (IQR, 13%-21%); and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%); PBB, 16.2% (IQR, 14%-17%); control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1beta increased in both bronchiectasis and PBB groups vs control subjects. CONCLUSIONS: A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to neutrophilic inflammation and NTHi colonization in both PBB and bronchiectasis. Whether this mechanism also contributes to the progression of PBB to bronchiectasis remains unknown. PMID- 26867835 TI - Risk of Active Tuberculosis in the Five Years Following Infection . . . 15%? AB - BACKGROUND: It is often stated that the lifetime risk of developing active TB after an index infection is 5% to 10%, one-half of which accrues in the 2 to 5 years following infection. The goal of this study was to determine whether such estimates are consistent with local programmatic data. METHODS: This study included close contacts of individuals with active pulmonary TB notified in the Australian state of Victoria from January 1, 2005, to December 31, 2013, who we deemed to have been infected as a result of their exposure. Survival analysis was first performed on the assumption of complete follow-up through to the end of the study period. The analysis was then repeated with imputation of censorship for migration, death, and preventive treatment, using local mortality and migration data combined with programmatic data on the administration of preventive therapy. RESULTS: Of 613 infected close contacts, 67 (10.9%) developed active TB during the study period. Assuming complete follow-up, the 1,650-day cumulative hazard was 11.5% (95% CI, 8.9-14.1). With imputation of censorship for death, migration, and preventive therapy, the median 1,650-day cumulative hazard over 10,000 simulations was 14.5% (95% CI, 11.1-17.9). Most risk accrued in the first 5 months after infection, and risk was greatest in the group aged < 5 years, reaching 56.0% with imputation, but it was also elevated in older children (27.6% in the group aged 5-14 years). CONCLUSIONS: The risk of active TB following infection is several-fold higher than traditionally accepted estimates, and it is particularly high immediately following infection and in children. PMID- 26867838 TI - Response. PMID- 26867839 TI - Idiopathic Pulmonary Fibrosis and Hypothyroidism: Cannot Forget Subclinical Disease and Difficult-to-Eliminate Corticosteroids. PMID- 26867840 TI - Noninvasive Ventilation and Risk of Leakage of Esophageal Anastomosis: A Matter of "Transesophageal Pressure"? PMID- 26867841 TI - Response. PMID- 26867842 TI - Response. PMID- 26867843 TI - Cardiac Biomarkers in Community-Acquired Pneumonia. PMID- 26867844 TI - Inhaled Tranexamic Acid as an Alternative for Hemoptysis Treatment. PMID- 26867845 TI - Merging Two Worlds: Point-of-Care Ultrasonography and Tele-Medicine. PMID- 26867846 TI - Method of Height Determination Used in Predicted Body Weight Equations. PMID- 26867847 TI - Commentary on the Study of the Efficacy of Lung Expansion Techniques on Alterations in Postoperative Pulmonary Complications. PMID- 26867848 TI - Controversies After Brain Death: When Families Ask for More. PMID- 26867849 TI - Bronchial Thermoplasty: Misleading Differences in Asthma Exacerbation Rates! PMID- 26867850 TI - Identifying Pathogen in Culture-Negative Pneumonia. PMID- 26867851 TI - Hepatopulmonary Syndrome in Patients With Cystic Fibrosis and Liver Disease. AB - Hepatopulmonary syndrome (HPS) is a liver-induced lung disorder defined as a triad of liver disease, pulmonary vascular dilatation, and a defect in oxygenation. It can complicate chronic liver disease of any etiology, but is most commonly associated with portal hypertension. Severe liver disease with portal hypertension is present in 2% to 8% of patients with cystic fibrosis (CF), but to date, to our knowledge, only one patient with CF has been reported to suffer from HPS. Here, we describe two patients with CF diagnosed with HPS, one subsequent to unresolved hypoxemia and the other following screening for HPS performed in our center. We speculate that HPS is underdiagnosed in patients with CF because of their coexisting respiratory morbidity, and we advocate routine screening for every patient with CF who has liver disease and portal hypertension. PMID- 26867852 TI - Refractory Case of Paroxysmal Autonomic Instability With Dystonia Syndrome Secondary to Hypoxia. AB - Paroxysmal autonomic instability with dystonia (PAID) is a syndrome commonly related to traumatic brain injury (TBI) and rarely to anoxia associated with symptoms of dystonia, tachycardia, tachypnea, and diaphoresis. This is a case of a 20-year-old man who was stabbed in the heart. He underwent surgical repair of a ventricular septal defect and mitral valve replacement. Postoperatively, he developed dystonia with tachycardia and tachypnea consistent with PAID syndrome, secondary to prolonged hypoxia. Traditionally, this poorly understood syndrome is treated with morphine, clonazepam, and nonselective beta-blockers. Second-line medications commonly used are baclofen, dantrolene, and gabapentin, which are aimed at the dystonia itself. In this case, both first- and second-line agents were ineffective. A 72-hour dexmedetomidine infusion resulted in complete resolution of symptoms. This is the first case of anoxia-induced PAID syndrome to be effectively treated with dexmedetomidine, which was previously used in a case induced by TBI. PMID- 26867853 TI - Two Patients With Hypotension and Respiratory Distress. PMID- 26867854 TI - Middle-Aged Woman With Shock. PMID- 26867855 TI - Chronic Cough and Bilateral Pneumothoraces in a Nonsmoker. AB - An 82-year-old Japanese nonsmoking man presented with persistent dry cough and small left apical pneumothorax. High resolution CT scan of the chest demonstrated bilateral upper lobe pleuroparenchymal thickening and architectural distortion. Serial imaging revealed mild progression and development of small bilateral pneumothoraces, and pneumomediastinum. A surgical lung biopsy was required to confirm the diagnosis. PMID- 26867856 TI - A 49-Year-Old Man With Cirrhosis and Pulmonary Fibrosis. AB - A 49-year-old man with a history of cryptogenic cirrhosis was referred to pulmonary clinic for evaluation prior to liver transplantation. Chest imaging obtained as part of the transplant workup had shown evidence of interstitial abnormalities. The patient noted shortness of breath on moderate exertion that was worsening over the past 2 to 3 years and associated with a nonproductive cough. He denied chest pain, chills, or fevers. His past medical history was significant for hypothyroidism. He did not have a history of alcohol consumption, smoking, or occupational exposures. He noted a family history of lung disease in his father and evidence of prominent clubbing in his sister and nephew. Workup for liver failure included a liver biopsy, which showed cirrhosis without evidence of autoimmune hepatitis. PMID- 26867857 TI - A 39-Year-Old Postpartum Woman With Foot Drop and Shortness of Breath. AB - A 39-year-old white woman with a history of adult-onset asthma, chronic sinusitis, and nasal polyposis presented to the ED with dyspnea and left lower extremity weakness and pain. Three months prior to her presentation she had an uncomplicated delivery of her second child, but during her pregnancy she experienced increasing asthma symptoms and nasal congestion. These symptoms progressed after delivery despite treatment with albuterol inhalers and antibiotics. PMID- 26867859 TI - The accuracy of biochemical interactions is ensured by endothermic stepwise kinetics. AB - The discerning behavior of living systems relies on accurate interactions selected from the lot of molecular collisions occurring in the cell. To ensure the reliability of interactions, binding partners are classically envisioned as finely preadapted molecules, selected on the basis of their affinity in one-step associations. But the counterselection of inappropriate interactions can in fact be much more efficiently obtained through difficult multi-step adjustment, whose final high energy state is locked by a fluctuation ratchet. The progressive addition of molecular bonds during stereo-adjustment can be modeled as a predominantly backward random walk whose first arrival is frozen by a micro irreversible transition. A new criterion of ligand specificity is presented, that is based on the ratio rejection/incorporation. In addition to its role in the selectivity of interactions, this generic recipe can underlie other important biological phenomena such as the regular synthesis at low level of supramolecular complexes, monostable kinetic bimodality, substrate concentration thresholds or the preparation of rapidly depolymerizable structures with stored energy, like microtubules. PMID- 26867860 TI - Diagnostic accuracy of a brief screening tool for attention deficit hyperactivity disorder in UK prison inmates. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties. METHOD: A cross-sectional study of 390 male prison inmates was performed in the UK, all participants were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2). RESULTS: A total of 47 (12.1%) inmates screened positive for ADHD using the full BAARS-IV, and 96 (24.6%) were clinically diagnosed, for a sensitivity of 37.9 and a specificity of 96.3. Our models identified the six items that most predicted ADHD diagnosis, with adjusted odds ratios ranging from 2.66 to 4.58. Sensitivity, specificity and accuracy were 0.82, 0.84 and 0.84, respectively, for the developed brief scale, and 0.71, 0.85 and 0.81 for its validation. Weighted probability scores produced an area under the curve of 0.89 for development, and 0.82 for validation of the brief scale. CONCLUSIONS: The original BAARS-IV performed poorly at identifying prison inmates with ADHD. Our developed brief scale substantially improved diagnostic accuracy. The brief screening instrument has great potential to be used as an accurate and resource-effective tool to screen young people and adults for likely ADHD in the criminal justice system. PMID- 26867861 TI - Using Time-Dependent Density Functional Theory to Probe the Nature of Donor Acceptor Stenhouse Adduct Photochromes. AB - We present the first theoretical investigation of a recently proposed class of photochromes, namely donor-acceptor Stenhouse adduct (DASA) switches [J. Am. Chem. Soc. 2014, 136, 8169-8172]. By using density functional theory and its time dependent counterpart, we investigate the ground- and excited-state structures, electronic transition energies, and several properties of the two isomeric forms. In addition to demonstrating that the selected level of theory is able to reproduce the main experimental facts, we show that 1) the two forms of the DASA photochromes are close to isoenergetic; 2) the two isomers possess similar total dipole moments, in spite of their very different sizes; 3) both isomers have a zwitterionic nature; 4) the nature of the dipole-allowed electronic excited state is vastly different in the two forms; and 5) the specific band shape of the extended DASA can be reproduced by vibronic calculations. PMID- 26867858 TI - Towards engineering carboxysomes into C3 plants. AB - Photosynthesis in C3 plants is limited by features of the carbon-fixing enzyme Rubisco, which exhibits a low turnover rate and can react with O2 instead of CO2 , leading to photorespiration. In cyanobacteria, bacterial microcompartments, known as carboxysomes, improve the efficiency of photosynthesis by concentrating CO2 near the enzyme Rubisco. Cyanobacterial Rubisco enzymes are faster than those of C3 plants, though they have lower specificity toward CO2 than the land plant enzyme. Replacement of land plant Rubisco by faster bacterial variants with lower CO2 specificity will improve photosynthesis only if a microcompartment capable of concentrating CO2 can also be installed into the chloroplast. We review current information about cyanobacterial microcompartments and carbon-concentrating mechanisms, plant transformation strategies, replacement of Rubisco in a model C3 plant with cyanobacterial Rubisco and progress toward synthesizing a carboxysome in chloroplasts. PMID- 26867862 TI - Characteristics of resistin in rheumatoid arthritis angiogenesis. AB - Adipokines have been reported to be involved in the regulation of various physiological processes, including the immune response. Rheumatoid arthritis (RA) is an example of a systemic immune disease that causes chronic inflammation of the synovium and bone destruction in the joint. Recent therapeutic strategies based on the understanding of the role of cytokines and cellular mechanisms in RA have improved our understanding of angiogenesis. On the other hand, endogenous endothelial progenitor cells, which are a population isolated from peripheral blood monocytes have recently been identified as a homing target for pro angiogeneic factor and vessel formation. In this review, we summarize the effects of common adipokines, such as adiponectin, leptin and resistin in RA pathogenesis and discuss other potential mechanisms of relevance for the therapeutic treatment of RA. PMID- 26867863 TI - Adherence to ribavirin in chronic hepatitis C patients on antiviral treatment: Results from a randomized controlled trial using real-time medication monitoring. AB - BACKGROUND AND OBJECTIVE: Adherence is essential in antiviral therapy for chronic hepatitis C. We investigated the effect of real-time medication monitoring on adherence to ribavirin. METHODS: In this randomized controlled trial, patients in the intervention group received a medication dispenser that monitored ribavirin intake real-time during 24 weeks PEG-interferon/ribavirin+/-boceprevir or telaprevir. Patients in the control group received standard-of-care. Adherence was also measured by pill count. RESULTS: Seventy-two patients were assigned to either intervention (n=35) or control groups (n=37). Median adherence by pill count was 96% (range: 43%-100%) with 30 (94%) of patients exhibiting>=80% adherence. Perfect adherence (i.e. 100%) was similar in intervention and control groups: 22 (85%) vs. 15 (75%) (P=0.47). Adherences by real-time medication monitoring and by pill count did not correlate (R=0.19, P=0.36). No predictors of poor adherence could be identified. Ribavirin trough levels after 8 weeks (median: 2.4 vs. 2.7mg/L, P=0.30) and 24 weeks (median: 3.0 vs. 3.0mg/L, P=0.69), and virological responses did not differ between intervention and control groups. CONCLUSIONS: Adherence to ribavirin during PEG-interferon containing therapy in chronic hepatitis C is high. Real-time medication monitoring did not influence adherence to ribavirin, plasma ribavirin levels or virological responses. PMID- 26867864 TI - Matrine compromises mouse sperm functions by a [Ca(2+)]i-related mechanism. AB - Matrine, a bioactive alkaloid widely used in Chinese medicine, inhibits mouse sperm functions in vitro. In this study, we investigated the reproductive toxicity of matrine to male mice in vivo. C57BL/6J mice were administered with daily doses of 0, 1, 10 and 50mg/kg matrine by intraperitoneal injection for 30 days. The results showed that matrine did not affect testis size, testis weight, sperm count and sperm viability, but it significantly inhibited total motility, progressive motility, linear velocity, capacitation and the progesterone-induced acrosome reaction of mouse sperm. Furthermore, the intracellular Ca(2+) concentration ([Ca(2+)]i), a key regulator of sperm function, was reduced in sperm of matrine-exposed mice. The current and gene expression of the sperm specific Ca(2+) channel, CatSper, which modulates Ca(2+) influx in sperm, were decreased in testes of matrine-exposed mice. These results indicate that matrine inhibits mouse sperm functions by a [Ca(2+)]i-related mechanism via CatSper channel. PMID- 26867865 TI - Sexual differentiation and reproductive development of female rat offspring after paternal exposure to the anti-tumor pharmaceutical cisplatin. AB - Cisplatin (CP) is used to treat a number of cancers, including testicular cancer. Studies indicate that CP-treatment can impair spermatogenesis in humans and rodents by germ cell DNA binding, through different modes of action. CP-paternal exposure resulted in adverse effects in F1 male offspring. In this study, F1 female offspring was assessed for reproductive development after CP-paternal exposure. Peri-pubertal male rats, treated with 1mg/Kg/day of CP or vehicle for 3 weeks, were mated with unexposed females. F1 female offspring of CP-treated fathers showed a decrease in fetal ovary germ cells, in estrous cycle length and FSH levels, and an increase in the percentage of antral follicles in adults. Based on our previous results and the findings of the present work we concluded that CP-paternal exposure leads to adverse effects on rat male and female reproductive development, raising concern, in humans, for children born to men exposed to CP. PMID- 26867867 TI - Development and pre-validation of an in vitro transactivation assay for detection of (anti)androgenic potential compounds using 22Rv1/MMTV cells. AB - The endocrine-disrupting effects of androgenic signaling play crucial roles in several androgen-related diseases. In attempting to develop an in vitro cell line to be used in androgen receptor (AR)-mediated reporter gene assays, we developed a stable 22Rv1/MMTV cell line, which is a human prostate cancer cell line that endogenously expresses functional AR, to evaluate AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established and optimized a test protocol for the AR-TA assay and validated the proposed assay using 20 compounds recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). All the performance parameters for agonist and antagonist assays were 91-100% comparable between the 22Rv1/MMTV assay and the ICCVAM report. In conclusion, the AR-TA assay using 22Rv1/MMTV cells might be a quick and relatively inexpensive method for screening large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription. PMID- 26867866 TI - Phthalate metabolite levels and menopausal hot flashes in midlife women. AB - During the menopausal transition, a woman's reproductive capacity declines, her hormone milieu changes, and her risk of hot flashes increases. Exposure to phthalates, which can be found in personal care products, can also result in altered reproductive function. Here, we investigated the associations between phthalate metabolite levels and midlife hot flashes. Eligible women (45-54 years of age) provided detailed information on hot flashes history and donated urine samples (n=195). Urinary phthalate metabolite levels were measured by HPLC-MS/MS. A higher total sum of phthalate metabolites commonly found in personal care products was associated with an increased risk of ever experiencing hot flashes (odds ratio (OR)=1.45; 95% confidence interval (CI)=1.07-1.96), hot flashes in the past 30days (OR=1.43; 95%CI=1.04-1.96), and more frequent hot flashes (OR=1.47; 95%CI=1.06-2.05). These data suggest that some phthalate exposures from personal care products are associated with menopausal hot flashes in women. PMID- 26867869 TI - Central Nervous System: Progress of Today and a Preview of Tomorrow. PMID- 26867868 TI - Facile, Fast-Responsive, and Photostable Imaging of Telomerase Activity in Living Cells with a Fluorescence Turn-On Manner. AB - In situ detecting and monitoring intracellular telomerase activity is significant for cancer diagnosis. In this work, we report a facile and fast-responsive bioprobe for in situ detection and imaging of intracellular telomerase activity with superior photostability. After transfected into living cells, quencher group labeled TS primer (QP) can be extended in the presence of intracellular telomerase. Positive charged TPE-Py molecules (AIE dye) will bind to the primer as well as extension repeated units, producing a telomerase activity-related turn on fluorescence signal. By incorporating positive charged AIE dye and substrate oligonucleotides, in situ light-up imaging and detection of intracellular telomerase activity were achieved. This strategy exhibits good performance for sensitive in situ tracking of telomerase activity in living cells. The practicality of this facile and fast-responsive telomerase detection method was demonstrated by using it to distinguish tumor cells from normal cells and to monitor the change of telomerase activity during treatment with antitumor drugs, which shows its potential in clinical diagnostic and therapeutic monitoring. PMID- 26867870 TI - Status of Radiation Therapy in Uruguay: Past, Present, and Future. PMID- 26867871 TI - Gray Anatomy: The Case of the Missing "s". PMID- 26867872 TI - Global Radiation Oncology From the Trainee Perspective: A View From Beyond the Bunker. PMID- 26867873 TI - Closing the Cancer Divide Through Ubuntu: Information and Communication Technology-Powered Models for Global Radiation Oncology. PMID- 26867875 TI - Impact of Expression of CD44, a Cancer Stem Cell Marker, on the Treatment Outcomes of Intensity Modulated Radiation Therapy in Patients With Oropharyngeal Squamous Cell Carcinoma. AB - PURPOSE: To investigate the significance of CD44 protein expression on the treatment outcomes of radiation therapy in patients with oropharyngeal squamous cell carcinoma (OPSCC) with or without p16 protein expression in the tumor tissue. METHODS AND MATERIALS: We reviewed the medical records of 58 OPSCC patients who had undergone radiation therapy and examined the tumor tissue expressions of CD44 and p16 protein by immunohistochemical staining. The correlations between the expressions of these proteins and the patients' treatment outcomes were analyzed. RESULTS: The data of 58 consecutive OPSCC patients who had undergone definitive intensity modulated radiation therapy were analyzed. The male/female ratio was 55:3, and the median age was 64 years. The clinical stage of the disease was stage II in 7 patients, stage III in 5 patients, stage IVA in 35 patients, and stage IVB in 11 patients. Of the patients, 79% received additional induction and/or concurrent chemotherapy. The median follow-up duration was 34 months. The 3-year overall survival, progression free survival (PFS) and locoregional control (LRC) rates of all the patients, regardless of the results of immunohistochemistry, were 73%, 64% and 76%, respectively. The PFS and LRC rates in the CD44(-) patients (86% and 93%, respectively) were significantly higher than those in the CD44(+) patients (57% and 70%, respectively). The PFS and LRC rates in the p16(+) patients (83% and 90%, respectively) were significantly higher than those in the p16(-) patients (45% and 61%, respectively). Patients who were CD44(-)/p16(+) showed the best LRC rates, and those who were CD44(+)/p16(-) showed the worst PFS and LRC rates among all the groups. CONCLUSIONS: Profiling of CD44 and p16 protein expressions by immunohistochemical staining is useful for predicting the treatment outcomes in patients with OPSCC undergoing definitive intensity modulated radiation therapy. PMID- 26867876 TI - Effect of Dosimetric Outliers on the Performance of a Commercial Knowledge-Based Planning Solution. AB - PURPOSE: RapidPlan, a commercial knowledge-based planning solution, uses a model library containing the geometry and associated dosimetry of existing plans. This model predicts achievable dosimetry for prospective patients that can be used to guide plan optimization. However, it is unknown how suboptimal model plans (outliers) influence the predictions or resulting plans. We investigated the effect of, first, removing outliers from the model (cleaning it) and subsequently adding deliberate dosimetric outliers. METHODS AND MATERIALS: Clinical plans from 70 head and neck cancer patients comprised the uncleaned (UC) ModelUC, from which outliers were cleaned (C) to create ModelC. The last 5 to 40 patients of ModelC were replanned with no attempt to spare the salivary glands. These substantial dosimetric outliers were reintroduced to the model in increments of 5, creating Model5 to Model40 (Model5-40). These models were used to create plans for a 10 patient evaluation group. Plans from ModelUC and ModelC, and ModelC and Model5-40 were compared on the basis of boost (B) and elective (E) target volume homogeneity indexes (HIB/HIE) and mean doses to oral cavity, composite salivary glands (compsal) and swallowing (compswal) structures. RESULTS: On average, outlier removal (ModelC vs ModelUC) had minimal effects on HIB/HIE (0%-0.4%) and sparing of organs at risk (mean dose difference to oral cavity and compsal/compswal were <=0.4 Gy). Model5-10 marginally improved compsal sparing, whereas adding a larger number of outliers (Model20-40) led to deteriorations in compsal up to 3.9 Gy, on average. These increases are modest compared to the 14.9 Gy dose increases in the added outlier plans, due to the placement of optimization objectives below the inferior boundary of the dose-volume histogram predicted range. CONCLUSIONS: Overall, dosimetric outlier removal from or addition of 5 to 10 outliers to a 70-patient model had marginal effects on resulting plan quality. Although the addition of >20 outliers deteriorated plan quality, the effect was modest. In this study, RapidPlan demonstrated robustness for moderate proportions of salivary gland dosimetric outliers. PMID- 26867874 TI - Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity. AB - PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistant and genetic hyperradiosensitive cases. METHODS AND MATERIALS: Immunofluorescence experiments were performed on a collection of skin fibroblasts from 12 radioresistant, 5 hyperradiosensitive, and 100 OR patients irradiated at 2 Gy. The numbers of micronuclei, gammaH2AX, and pATM foci that reflect different steps of DNA double-strand breaks (DSB) recognition and repair were assessed from 10 minutes to 24 hours after irradiation and plotted against the severity grades established by the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group. RESULTS: OR patients did not necessarily show a gross DSB repair defect but a systematic delay in the nucleoshuttling of the ATM protein required for complete DSB recognition. Among the radiobiological factors, the maximal number of pATM foci provided the best discrimination among OR patients and a significant correlation with each OR severity grade, independently of tumor localization and of the early or late nature of reactions. CONCLUSIONS: Our results are consistent with a general classification of human radiosensitivity based on 3 groups: radioresistance (group I); moderate radiosensitivity caused by delay of nucleoshuttling of ATM, which includes OR patients (group II); and hyperradiosensitivity caused by a gross DSB repair defect, which includes fatal cases (group III). PMID- 26867877 TI - Deep Inspiration Breath Hold-Based Radiation Therapy: A Clinical Review. AB - Several recent developments in linear accelerator-based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effects in general, particularly breathing motion. Intrafractional breathing related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT. PMID- 26867879 TI - Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis. AB - PURPOSE: To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers. METHODS AND MATERIALS: The PubMed, Web of Science, Cochrane Library, and ClinicalTrials were searched to identify randomized, controlled trials studying the effect of concomitant administration of pilocarpine for radiation-induced xerostomia. Included trials were systematically reviewed, and quantifiable outcomes were pooled for meta-analysis. Outcomes of interest included salivary flow, clinician rated xerostomia grade, patient-reported xerostomia scoring, quality of life, and adverse effects. RESULTS: Six prospective, randomized, controlled trials in 8 articles were included in this systematic review. The total number of patients was 369 in the pilocarpine group and 367 in the control group. Concomitant administration of pilocarpine during radiation could increase the unstimulated salivary flow rate in a period of 3 to 6 months after treatment, and also reduce the clinician-rated xerostomia grade. Patient-reported xerostomia was not significantly impacted by pilocarpine in the initial 3 months but was superior at 6 months. No significant difference of stimulated salivary flow rate could be confirmed between the 2 arms. Adverse effects of pilocarpine were mild and tolerable. CONCLUSIONS: The concomitant administration of pilocarpine during radiation increases unstimulated salivary flow rate and reduces clinician-rated xerostomia grade after radiation. It also relieves patients' xerostomia at 6 months and possibly at 12 months. However, pilocarpine has no effect on stimulated salivary flow rate. PMID- 26867880 TI - Cost-Effectiveness Analysis of Chemoradiation Therapy Versus Transoral Robotic Surgery for Human Papillomavirus-Associated, Clinical N2 Oropharyngeal Cancer. AB - PURPOSE: To perform a cost-effectiveness analysis of primary chemoradiation therapy (CRT) versus transoral robotic surgery (TORS) for clinical N2, human papillomavirus (HPV)-positive oropharyngeal carcinoma. METHODS AND MATERIALS: We developed a Markov model to describe the health states after treatment with CRT or TORS, followed by adjuvant radiation therapy or CRT in the presence of high risk pathology (positive margins or extracapsular extension). Outcomes, toxicities, and costs were extracted from the literature. One-way sensitivity analyses (SA) were performed over a wide range of parameters, as were 2-way SA between the key variables. Probabilistic SA and value of information studies were performed over key parameters. RESULTS: The expected quality-adjusted life years (QALYs)/total costs for CRT and TORS were 7.31/$50,100 and 7.29/$62,200, respectively, so that CRT dominated TORS. In SA, primary CRT was almost always cost-effective up to a societal willingness-to-pay of $200,000/QALY, unless the locoregional recurrence risk after TORS was 30% to 50% lower, at which point it became cost effective at a willingness-to-pay of $50-100,000/QALY. Probabilistic SA confirmed the importance of locoregional recurrence risk, and the value of information in precisely knowing this parameter was more than $7M per year. If the long-term utility after TORS was 0.03 lower than CRT, CRT was cost-effective over nearly any assumption. CONCLUSIONS: Under nearly all assumptions, primary CRT was the cost-effective therapy for HPV-associated, clinical N2 OPC. However, in the hypothetical event of a large relative improvement in LRR with surgery and equivalent long-term utilities, primary TORS would become the higher-value treatment, arguing for prospective, comparative study of the 2 paradigms. PMID- 26867878 TI - Patterns of Local-Regional Management Following Neoadjuvant Chemotherapy in Breast Cancer: Results From ACOSOG Z1071 (Alliance). AB - PURPOSE: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC. METHODS AND MATERIALS: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors. RESULTS: Of 401 node-positive patients, mastectomy was performed in 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group. CONCLUSIONS: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice patterns conflict with expert recommendations and ongoing trial guidelines. There is a significant need for greater uniformity and guidelines regarding RT following NAC. PMID- 26867883 TI - Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery. AB - PURPOSE: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. METHODS AND MATERIALS: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. RESULTS: With a median follow up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). CONCLUSIONS: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an increased risk for the development of LMD. PMID- 26867882 TI - Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids: Feasibility and Early Results. AB - PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immediate perioperative high-dose-rate brachytherapy; 3 patients had been previously treated with adjuvant external beam radiation therapy and presented with recurrences in the pretreated areas. Two or more different treatment modalities had been tried in all patients and had failed to achieve remission. After (re )excision of the keloids, a single brachytherapy tube was placed subcutaneously before closing the wound. The target volume covered the scar in total length. Brachytherapy was given in 3 fractions with a single dose of 6 Gy in 5 mm tissue depth. The first fraction was given within 6 hours after surgery, the other 2 fractions on the first postoperative day. Thus, a total dose of 18 Gy in 3 fractions was administered within 36 hours after the resection. RESULTS: The treatment was feasible in all patients. No procedure-related complications (eg, secondary infections) occurred. Nineteen patients had keloid-related symptoms before treatment like pain and pruritus; disappearance of symptoms was noticed in all patients after treatment. After a median follow-up of 29.4 months (range, 7.9 72.4 months), 2 keloid recurrences and 2 mildly hypertrophied scars were observed. The local control rate was 94%. Pigmentary abnormalities were detected in 3 patients, and an additional 6 patients had a mild delay in the wound-healing process. CONCLUSIONS: The early results of this study prove the feasibility and the efficacy of brachytherapy for the prevention of keloids. The results also suggest that brachytherapy may be advantageous in the management of high-risk keloids or as salvage treatment for failure after external beam therapy. PMID- 26867881 TI - The Influence of Diabetes Mellitus and Metformin on Distant Metastases in Oropharyngeal Cancer: A Multicenter Study. AB - PURPOSE: Local control in oropharyngeal cancer has improved to unprecedented rates with combined modality therapy; as a result, distant metastases are becoming a principal challenge. We aimed to determine the impact of diabetes mellitus and metformin use on clinical outcomes in a large population of oropharyngeal cancer patients treated in the modern era. METHODS AND MATERIALS: We identified 1745 consecutive patients with oropharyngeal cancer treated at 2 large cancer centers with external beam radiation therapy from 1998 to 2011. A total of 184 patients had diabetes mellitus at the time of diagnosis, of whom 102 were taking metformin. The outcomes assessed included local failure-free survival (LFFS), regional failure-free survival (RFFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: The median follow-up time was 4.3 years. The 5-year actuarial rates of DMFS were 89.6% for nondiabetic patients and 78.7% for diabetic nonmetformin users (P=.011) and of OS were 83.0% for nondiabetic patients and 70.7% for diabetic nonmetformin users (P=.048). Diabetic metformin users had 5-year DMFS (90.1%) and OS (89.6%) similar to those of nondiabetic patients. Multivariate analysis (diabetic nonmetformin users as reference) demonstrated improved DMFS for nondiabetic patients (adjusted hazard ratio 0.54; 95% confidence interval 0.32-0.93; P=.03) and a trend toward improved DMFS with metformin use (adjusted hazard ratio 0.46; 95% confidence interval 0.20 1.04; P=.06). LFFS and RFFS were high in all groups and were not significantly different by diabetic status or metformin use. CONCLUSIONS: Diabetic patients not using metformin independently have significantly higher rates of distant metastases than do nondiabetic patients, whereas metformin users have rates of distant metastases similar to those of nondiabetic patients. Further prospective investigation is warranted to validate the benefit of metformin in oropharyngeal cancer. PMID- 26867884 TI - Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer. AB - PURPOSE: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). METHODS AND MATERIALS: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. RESULTS: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of >=0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). CONCLUSIONS: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of >=0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection. PMID- 26867886 TI - Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma. AB - PURPOSE: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). METHODS AND MATERIALS: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. RESULTS: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. CONCLUSIONS: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial. PMID- 26867885 TI - Lymphocyte-Sparing Effect of Stereotactic Body Radiation Therapy in Patients With Unresectable Pancreatic Cancer. AB - PURPOSE: Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS AND MATERIALS: Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy * 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy * 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival. RESULTS: Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm(3)) than in CRT (344.6 cm(3); P<.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC <500 cells/mm(3) vs 13.8% of SBRT patients; P<.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002). CONCLUSIONS: SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted. PMID- 26867887 TI - Value of Magnetic Resonance Imaging Without or With Applicator in Place for Target Definition in Cervix Cancer Brachytherapy. AB - PURPOSE: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTVHR) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). METHODS AND MATERIALS: The CTVHR was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTVHR CTClinical) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTVHR-CTpre-BT MRI). The CT contours were compared with reference contours on MRI with the applicator in place (CTVHR-MRIref). Width, height, thickness, volumes, and topography were analyzed. RESULTS: The CT-MRIref differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTVHR-CTpre-BT MRI-MRIref volume differences (2.6 cm(3) [IIB], 7.3 cm(3) [IIIB]) were superior to CTVHR-CTClinical-MRIref (11.8 cm(3) [IIB], 22.9 cm(3) [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTVHR-CTpre-BT MRI. In 5 of 12 cases, MRIref contours were partly missed on CT. CONCLUSIONS: Pre-BT MRI helps to define CTVHR before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTVHR-CT is expected in stage IB tumors. PMID- 26867888 TI - Image Guided Cervical Brachytherapy: 2014 Survey of the American Brachytherapy Society. AB - PURPOSE: To provide an update of the 2007 American brachytherapy survey on image based brachytherapy, which showed that in the setting of treatment planning for gynecologic brachytherapy, although computed tomography (CT) was often used for treatment planning, most brachytherapists used point A for dose specification. METHODS AND MATERIALS: A 45-question electronic survey on cervical cancer brachytherapy practice patterns was sent to all American Brachytherapy Society members and additional radiation oncologists and physicists based in the United States between January and September 2014. Responses from the 2007 survey and the present survey were compared using the chi(2) test. RESULTS: There were 370 respondents. Of those, only respondents, not in training, who treat more than 1 cervical cancer patient per year and practice in the United States, were included in the analysis (219). For dose specification to the target (cervix and tumor), 95% always use CT, and 34% always use MRI. However, 46% use point A only for dose specification to the target. There was a lot of variation in parameters used for dose evaluation of target volume and normal tissues. Compared with the 2007 survey, use of MRI has increased from 2% to 34% (P<.0001) for dose specification to the target. Use of volume-based dose delineation to the target has increased from 14% to 52% (P<.0001). CONCLUSION: Although use of image-based brachytherapy has increased in the United States since the 2007 survey, there is room for further growth, particularly with the use of MRI. This increase may be in part due to educational initiatives. However, there is still significant heterogeneity in brachytherapy practice in the United States, and future efforts should be geared toward standardizing treatment. PMID- 26867889 TI - Image Guided Hypofractionated Postprostatectomy Intensity Modulated Radiation Therapy for Prostate Cancer. AB - PURPOSE: Hypofractionated radiation therapy (RT) has promising long-term biochemical relapse-free survival (bRFS) with comparable toxicity for definitive treatment of prostate cancer. However, data reporting outcomes after adjuvant and salvage postprostatectomy hypofractionated RT are sparse. Therefore, we report the toxicity and clinical outcomes after postprostatectomy hypofractionated RT. METHODS AND MATERIALS: From a prospectively maintained database, men receiving image guided hypofractionated intensity modulated RT (HIMRT) with 2.5-Gy fractions constituted our study population. Androgen deprivation therapy was used at the discretion of the radiation oncologist. Acute toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Biochemical recurrence was defined as an increase of 0.1 in prostate-specific antigen (PSA) from posttreatment nadir or an increase in PSA despite treatment. The Kaplan-Meier method was used for the time-to-event outcomes. RESULTS: Between April 2008 and April 2012, 56 men received postoperative HIMRT. The median follow-up time was 48 months (range, 21-67 months). Thirty percent had pre-RT PSA <0.1; the median pre RT detectable PSA was 0.32 ng/mL. The median RT dose was 65 Gy (range, 57.5-65 Gy). Ten patients received neoadjuvant and concurrent hormone therapy. Posttreatment acute urinary toxicity was limited. There was no acute grade 3 toxicity. Late genitourinary (GU) toxicity of any grade was noted in 52% of patients, 40% of whom had pre-RT urinary incontinence. The 4-year actuarial rate of late grade 3 GU toxicity (exclusively gross hematuria) was 28% (95% confidence interval [CI], 16%-41%). Most grade 3 GU toxicity resolved; only 7% had persistent grade >=3 toxicity at the last follow-up visit. Fourteen patients experienced biochemical recurrence at a median of 20 months after radiation. The 4-year bPFS rate was 75% (95% CI, 63%-87%). CONCLUSIONS: The biochemical control in this series appears promising, although relatively short follow-up may lead to overestimation. Late grade 3 GU toxicity was higher than anticipated with hypofractionated radiation of 65 Gy to the prostate bed, although most resolved. PMID- 26867891 TI - Radiation Therapy-First Strategy After Surgery With or Without Adjuvant Chemotherapy in Stage IIIA-N2 Non-Small Cell Lung Cancer. AB - PURPOSE: Postoperative radiation therapy (PORT) and postoperative chemotherapy (POCT) can be administered as adjuvant therapies in patients with non-small cell lung cancer (NSCLC). The aim of this study was to present the clinical outcomes in patients treated with PORT-first with or without subsequent POCT in stage IIIA N2 NSCLC. METHODS AND MATERIALS: From January 2002 to November 2014, the conditions of 105 patients with stage IIIA-N2 NSCLC who received PORT-first with or without subsequent POCT were analyzed. PORT was initiated within 4 to 6 weeks after surgical resection. Platinum-based POCT was administered 3 to 4 weeks after the completion of PORT. We analyzed the outcomes and the clinical factors affecting survival. RESULTS: Of 105 patients, 43 (41.0%) received POCT with a median of 4 cycles (range, 2-6 cycles). The follow-up times ranged from 3 to 123 months (median, 30 months), and the 5-year overall survival (OS) was 40.2%. The 5 year OS of patients treated with PORT and POCT was significantly higher than that of patients with PORT (61.3% vs 29.2%, P<.001). The significant prognostic factors affecting OS were the use of POCT (hazard ratio [HR] = 0.453, P=.036) and type of surgery (pneumonectomy/lobectomy; HR = 2.845, P<.001). CONCLUSIONS: PORT first strategy after surgery appeared not to compromise the clinical outcomes in the treatment of stage IIIA-N2 NSCLC. The benefit of POCT on OS was preserved even in the PORT-first setting. Further studies are warranted to compare the sequencing of PORT and POCT, guaranteeing the proper use of POCT. PMID- 26867892 TI - Audiovisual Biofeedback Improves Cine-Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency. AB - PURPOSE: To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients. METHODS AND MATERIALS: Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio. RESULTS: Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001). CONCLUSIONS: These results demonstrated that AV biofeedback significantly improved intra- and interfraction lung tumor motion consistency for lung cancer patients. These results demonstrate that AV biofeedback can facilitate consistent tumor motion, which is advantageous toward achieving more accurate medical imaging and radiation therapy procedures. PMID- 26867893 TI - In Regard to Wu et al. PMID- 26867890 TI - Factors Associated With Early Mortality in Patients Treated With Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer. AB - PURPOSE: Concurrent chemoradiation therapy (con-CRT) is recommended for fit patients with locally advanced non-small cell lung cancer (LA-NSCLC) but is associated with toxicity, and observed survival continues to be limited. Identifying factors associated with early mortality could improve patient selection and identify strategies to improve prognosis. METHODS AND MATERIALS: Analysis of a multi-institutional LA-NSCLC database consisting of 1245 patients treated with con-CRT in 13 institutions was performed to identify factors predictive of 180-day survival. Recursive partitioning analysis (RPA) was performed to identify prognostic groups for 180-day survival. Multivariate logistic regression analysis was used to create a clinical nomogram predicting 180-day survival based on important predictors from RPA. RESULTS: Median follow up was 43.5 months (95% confidence interval [CI]: 40.3-48.8) and 127 patients (10%) died within 180 days of treatment. Median, 180-day, and 1- to 5-year (by yearly increments) actuarial survival rates were 20.9 months, 90%, 71%, 45%, 32%, 27%, and 22% respectively. Multivariate analysis adjusted by region identified gross tumor volume (GTV) (odds ratio [OR] >=100 cm(3): 2.61; 95% CI: 1.10-6.20; P=.029) and pulmonary function (forced expiratory volume in 1 second [FEV1], defined as the ratio of FEV1 to forced vital capacity [FVC]) (OR <80%: 2.53; 95% CI: 1.09-5.88; P=.030) as significant predictors of 180-day survival. RPA resulted in a 2-class risk stratification system: low-risk (GTV <100 cm(3) or GTV >=100 cm(3) and FEV1 >=80%) and high-risk (GTV >=100 cm(3) and FEV1 <80%). The 180-day survival rates were 93% for low risk and 79% for high risk, with an OR of 4.43 (95% CI: 2.07-9.51; P<.001), adjusted by region. A clinical nomogram predictive of 180-day survival, incorporating FEV1, GTV, N stage, and maximum esophagus dose yielded favorable calibration (R(2) = 0.947). CONCLUSIONS: This analysis identified several risk factors associated with early mortality and suggests that future research in the optimization of pretreatment pulmonary function and/or functional lung avoidance treatment may alter the therapeutic ratio in this patient population. PMID- 26867894 TI - Erratum. In Regard to Onimaru et al. PMID- 26867895 TI - Erratum. A randomized phase 2 study comparing 2 stereotactic body radiation therapy schedules for medically inoperable patients with stage I peripheral non small cell lung cancer: NRG Oncology RTOG 0915 (NCCTG N0927). PMID- 26867898 TI - [Not Available]. PMID- 26867899 TI - Celeribacter persicus sp. nov., a polycyclic-aromatic-hydrocarbon-degrading bacterium isolated from mangrove soil. AB - A Gram-stain-negative, mesophilic bacterial strain, designated SBU1T, which degrades polycyclic aromatic hydrocarbons was isolated from the sediments of the mangrove forests of Nayband Bay in the Iranian Persian Gulf during a bioremediation experiment. The 16S rRNA gene sequence of strain SBU1T exhibited highest similarities with Celeribacter indicus P73T (98.52%) and Celeribacter neptunius H 14T (97.05%). Phylogenetic analysis, based on 16S rRNA gene sequences, demonstrated that strain SBU1T fell within a cluster consisting of the type strains of species of the genus Celeribacter and formed a stable clade with C. indicus P73T in trees generated with three algorithms. The fatty acid profile of strain SBU1T consisted of the major fatty acids C18:1omega7c/omega6c and C18:1omega7c 11-methyl. The major compounds in the polar lipid profile were one phosphatidylglycerol and four unidentified phospholipids. The quinone system exclusively comprised ubiquinone (Q-10). The DNA G+C content was 60.4 mol%. A combination of phylogenetic analysis, DNA-DNA hybridization estimation, average nucleotide identity results and differential phenotypic and chemotaxonomic characteristics demonstrated that strain SBU1T could be distinguished from its close relatives. Therefore, strain SBU1T is considered to represent a novel species of the genus Celeribacter for which the name Celeribacter persicus sp. nov. is proposed. The type strain is SBU1T (=MCCC 1A00672T=DSM 100434T). PMID- 26867900 TI - The zinc transporter ZNT3 co-localizes with insulin in INS-1E pancreatic beta cells and influences cell survival, insulin secretion capacity, and ZNT8 expression. AB - Zinc trafficking in pancreatic beta cells is tightly regulated by zinc transporting (ZNTs) proteins. The role of different ZNTs in the beta cells is currently being clarified. ZNT8 transports zinc into insulin granules and is critical for a correct insulin crystallization and storage in the granules whereas ZNT3 knockout negatively affects beta cell function and survival. Here, we describe for the first time the sub-cellular localization of ZNT3 by immuno gold electron microscopy and supplement previous data from knockout experiments with investigations of the effect of ZNT3 in a pancreatic beta cell line, INS-1E overexpressing ZNT3. In INS-1E cells, we found that ZNT3 was abundant in insulin containing granules located close to the plasma membrane. The level of ZNT8 mRNA was significantly decreased upon over-expression of ZNT3 at different glucose concentrations (5, 11 and 21 mM glucose). ZNT3 over-expression decreased insulin content and insulin secretion whereas ZNT3 over-expression improved the cell survival after 24 h at varying glucose concentrations (5, 11 and 21 mM). Our data suggest that ZNT3 and ZNT8 (known to regulate insulin secretion) have opposite effects on insulin synthesis and secretion possibly by a transcriptional co regulation since mRNA expression of ZNT3 was inversely correlated to ZNT8 and ZNT3 over-expression reduced insulin synthesis and secretion in INS-1E cells. ZNT3 over-expression improved cell survival. PMID- 26867901 TI - Isolated recto-sigmoid colitis: a new imaging pattern of ipilimumab-associated colitis. AB - PURPOSE: The purpose of this study is to describe typical CT findings and distinct imaging patterns of ipilimumab-associated colitis in immunotherapeutic treatment of melanoma. MATERIALS AND METHODS: This HIPAA-compliant retrospective study included 86 patients with melanoma imaged with CT or PET/CT of the abdomen and pelvis during or shortly after administration of ipilimumab. Twelve of 86 patients (14%) developed symptoms of colitis and underwent CT imaging of the abdomen and pelvis while symptomatic. Two radiologists reviewed CT images to evaluate for the presence of CT findings of colitis including mesenteric vessel engorgement, pericolonic inflammatory change, hyperenhancement of colonic mucosa, colonic wall thickening, fluid-filled colonic distension, pneumoperitoneum, pneumatosis, and diverticulosis in the inflamed segment of colon. One nuclear medicine radiologist reviewed PET images for abnormally increased FDG uptake in the colon. The diagnosis of ipilimumab-associated colitis was made based on clinical presentation, imaging findings, and laboratory data. RESULTS: Common CT findings of ipilimumab-associated colitis included colonic mucosal hyperenhancement (10/12 [83%]), mesenteric vessel engorgement (9/12 [75.0%]), colonic wall thickening (9/12 [75%]), and pericolonic fat stranding (2/12 [16%]). No patient developed pneumatosis or pneumoperitoneum. Diffuse colitis was present in 4/12 (33%) patients. Segmental colitis with associated diverticulosis (was present in 2/12 (17%) patients). A third pattern, isolated recto-sigmoid colitis without diverticulosis, was observed in 6/12 (50%) patients. All patients with colitis demonstrated recto-sigmoid involvement. CONCLUSIONS: A third radiologic pattern of ipilimumab-associated colitis was observed in this study: isolated recto-sigmoid colitis without diverticulosis. All patterns of ipilimumab associated colitis include recto-sigmoid involvement. PMID- 26867902 TI - MRI for pelvic floor dysfunction: can the strain phase be eliminated? AB - PURPOSE: The purpose of the study was to determine if the strain phase of an MR defecography (MRD) protocol is redundant and can be eliminated without a loss of diagnostic information. MATERIALS AND METHODS: Institutional review board approval was obtained and the requirement for informed consent was waived. A retrospective single-center review of 80 MRD examinations (68 female, 12 male, mean age 55 years old) was conducted. Two radiologists blinded to patient information evaluated in consensus the strain and evacuation phases separately and in a random order. Each phase was assessed for the presence and degree of posterior compartment descent, cystocele, urethral hypermobility, uterovaginal prolapse, rectocele, rectal intussusception, and enterocele. The degree of pelvic floor descent was compared using a paired t test and McNemar's test was used to compare the proportion of abnormal findings. RESULTS: The evacuation phase identified all abnormalities identified on the strain phase and also identified both additional and more pronounced abnormalities, including an additional 34 cystoceles, 20 cases of urethral hypermobility, 13 uterovaginal prolapses, 36 rectoceles, 5 rectal intussusceptions, and 6 enteroceles (all p < 0.02). The mean posterior compartment descent was 24.1 mm greater on the evacuation phase than the strain phase (p < 0.0001). CONCLUSION: The strain phase is redundant and we propose that it can be eliminated from a routine MRD protocol. This will help streamline the examination, simplify patient instructions, and reduce both imaging and reporting time. PMID- 26867903 TI - How to not miss alveolar echinococcosis in hepatic lesions suspicious for cholangiocellular carcinoma. AB - PURPOSE: Hepatic alveolar echinococcosis (AE) resembles intrahepatic cholangiocarcinoma (ICC) on radiological imaging. The purpose of this study was to identify criteria to discriminate AE from ICC with CT and MR Imaging. METHODS: One hundred and sixteen imaging studies of 94 patients (CT n = 65; MRI n = 51) diagnosed with AE (n = 55) or ICC (n = 39) were retrospectively reviewed by two blinded radiologists for lesion features including enhancement pattern and matrix composition. A consensus read was conducted in cases of disagreement. Uni- and multivariate logistic regression with bootstrapping were used for analysis. RESULTS: Using CT, no or septal enhancement and calcification yielded the highest values of sensitivity/specificity (90.9%/90.6% and 81.8%/96.9%) for AE. Using MRI, no or septal enhancement and cystic components achieved the highest sensitivity/specificity (90.9%/100.0% and 84.8%/66.7%) for AE. Multivariate logistic regression identified the following strong independent predictors for AE: for MRI, no or septal enhancement (odds ratio [OR] 322.4; p < 0.001); for CT, no or septal enhancement and calcification (OR 35.9 and 42.5; p < 0.001 and p < 0.01, respectively). No or septal enhancement and calcification demonstrated the highest interreader agreement (>90%). CONCLUSION: Enhancement characteristics and matrix calcifications offer the strongest discriminating potential between AE and ICC with a high sensitivity, specificity, and interreader agreement. PMID- 26867904 TI - Diffusion-weighted and hepatobiliary phase gadoxetic acid-enhanced quantitative MR imaging for identification of complete pathologic response in colorectal liver metastases after preoperative chemotherapy. AB - PURPOSE: To evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and gadoxetic acid-enhanced magnetic resonance imaging (MRI) to differentiate colorectal liver metastasis (CRLM) with complete pathologic response from those with incomplete response in patients treated with preoperative chemotherapy. METHODS: Gadoxetic acid-enhanced liver MRI and DWI were performed after completion of preoperative chemotherapy in patients with CRLM scheduled for liver resection. Metastases were classified as those with complete pathologic response (CR-CRLM) or incomplete response (IR-CRLM) according to postsurgical histopathology. Quantitative analysis was performed on non contrast-enhanced images and hepatobiliary phase images following gadoxetic acid administration. Apparent diffusion coefficient values (ADC), normalized relative enhancement (NRE), and relative signal intensity difference (RSID) along with their diagnostic measures for detection of CR-CRLM were calculated for all lesions. RESULTS: In 23 patients, 10 CR-CRLM and 35 IR-CRLM (mean diameter, 21.2 mm) were evaluated. In CR-CRLM, ADC was significantly higher after exclusion of the outliers (p = 0.030); and RSID was significantly lower (p = 0.008). Combined indices range of ADC = 1.25-1.9 * 10(-3) mm(2)/s, NRE = 0-35% and RSID <120 had 60% sensitivity and 100% specificity for detection of CR-CRLM. CONCLUSION: DWI and gadoxetic acid-enhanced MRI appear promising for the detection of CRLM with complete response to preoperative chemotherapy. This could have significant implications for liver resection planning after preoperative chemotherapy. PMID- 26867905 TI - Non-invasive assessment of liver fibrosis using acoustic structure quantification: comparison with transient elastography in chronic viral hepatitis. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic efficacy of acoustic structure quantification (ASQ) parameters [mode, average, and focal distribution (FD) ratio] in the staging of hepatic fibrosis in patients with chronic viral hepatitis and to compare it with transient elastography (TE) by using liver biopsy as reference standard. METHODS: We studied 62 patients with chronic viral hepatitis. Each patient underwent ASQ evaluation and liver biopsy; 54 of these patients received TE. Thirty-six participants without any liver disease were enrolled as normal group, who also underwent ASQ evaluation and TE. All three parameters of ASQ were compared with the histologic fibrosis grade according to the METAVIR scoring (F0-F4). Statistical analysis was performed to investigate the correlations and the diagnostic values of ASQ parameters and compare them to TE. RESULTS: All three ASQ parameters and TE were significantly correlated with liver fibrosis stage. Of the ASQ parameters, the mode parameter showed the best correlation (P < 0.001). On the area under the receiver operating characteristic curve (AUROC), the mode parameter of ASQ analysis showed both significant correlation and good accuracy for diagnosis of F >= 1, F >= 2, and F >= 3. These values were significantly better than those of the average and FD ratio parameters in F >= 1 and F >= 2 (P < 0.05). There was no statistically significant difference in AUROC between the mode parameter and TE in diagnosis of F >= 1, F >= 2, or F >= 3. CONCLUSIONS: The mode parameter is the most reliable ASQ parameter, comparable to TE, as a non-invasive method for the detection and grading of liver fibrosis in patients with chronic viral hepatitis. PMID- 26867906 TI - Comparison of CT and contrast-enhanced ultrasound findings in hepatic angiomyolipoma with pathological correlations. AB - OBJECTIVE: To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. METHODS: Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. RESULTS: Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. CONCLUSION: There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs. PMID- 26867907 TI - Comparison of tumor vascularity and hemodynamics in three rat hepatoma models. AB - PURPOSE: To compare tumor vascularity and hemodynamics in three rat hepatoma models: N1-S1 cells in Sprague-Dawley rats, McA-RH7777 cells in Sprague-Dawley rats, and 13762 MAT B III cells in F344 rats. METHODS: The three rat hepatoma models were induced in five rats per group. After confirming that the tumors grew up to 10 mm on magnetic resonance imaging, the rats underwent dynamic contrast enhanced ultrasonography (DCE-US). Afterward, the rats were euthanized for histologic analyses. The Kruskal-Wallis test was used to compare the rat hepatoma models. Correlation coefficients were calculated between the microvessel density (MVD) and DCE-US parameters. RESULTS: On DCE-US imaging, arterial enhancement and washout were demonstrated in all N1-S1 tumors, while persistent peripheral enhancement on arterial to portal phases was shown in all 13762 MAT B III tumors. The McA-RH7777 tumors presented diverse enhancement patterns on arterial and portal phases. There were no significant differences in DCE-US parameters among the three hepatoma groups, while MVD was correlated with peak intensity (r = 0.565, p = 0.044), mean transit time (r = -0.559, p = 0.047), and time to peak (r = - 0.617, p = 0.025) of individual rats. The necrosis ratio was significantly different between the models (p = 0.031); 13762 MAT B III showed a significantly higher necrosis ratio than N1-S1 (p < 0.050 by post hoc test). CONCLUSION: The N1 S1 tumor may be suitable as a model to investigate hypervascular hepatic tumors of the liver in DCE-US such as hepatocellular carcinoma among the three tumors. PMID- 26867908 TI - Focal hepatic solid lesions incidentally detected on initial ultrasonography in 542 asymptomatic patients. AB - PURPOSE: The purpose of this study is to evaluate the clinical significance of focal hepatic solid lesions incidentally detected on initial ultrasonography in asymptomatic patients. METHODS: From January 2009 to December 2009, 2670 initial ultrasonographies were performed in asymptomatic population. Of these 2670 initial examinations, 681 focal hepatic solid lesions in 542 patients (mean 39.4 years, range 23-73 years) were detected. Clinical information, ultrasonography features, and the outcome of these lesions were analyzed. RESULTS: Six hundred and seventy four lesions (99.0%) in 539 patients (99.4%) were benign, while seven lesions (1.0%) in three patients (0.6%) proved to be malignant. Risk factors significantly associated with malignant focal hepatic solid lesions were known history of malignancy, history of hepatitis, a positive result for the hepatitis B surface antigen, and abnormally elevated tumor markers. No malignancy was identified in patients without any one of these four risk factors. Ultrasonographic features of internal heterogeneous echotexture with peripheral hypoechoic rim showed significant associations with malignancy. CONCLUSIONS: Focal hepatic solid lesions incidentally detected on initial ultrasonography were rarely malignant, especially in patients without these risk factors. Therefore, the knowledge of these risk factors and US features is important in order to make a differential diagnosis between benign and malignant focal hepatic lesions. PMID- 26867909 TI - CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy. AB - PURPOSE: The objectives of this retrospective study were to describe the characteristics and topography of pancreatic ductal adenocarcinoma and its early local recurrence after pancreaticoduodenectomy and identify predictive factors of local early recurrence by imaging computed tomography (CT). METHODS: The institutional review board approved the study and did require additional informed consent for reviewing the patients' medical records and images. Patients who underwent pancreaticoduodenectomy for ductal adenocarcinoma, a preoperative CT scan, and adequate postoperative CT were included. After postoperative imaging, correlations among clinical and histological characteristics and preoperative imaging were evaluated. RESULTS: Among the 123 patients who underwent pancreaticoduodenectomy, 48 patients had sufficient follow-up imaging and were included in this study. A total of 33 patients experienced local early recurrence (Group 1), and 15 exhibited no local recurrence (Group 2). Local recurrence consisted of two types of anomalies: tissue nodules on surgical clips (94%) and peri-arterial encasement (82%). On preoperative imaging, the tumor diameter (p = 0.02) and the presence of a venous borderline resectable tumor (p < 0.0001) were predictive of local recurrence. CONCLUSIONS: Tissue nodules on surgical clips and arterial encasement characterize early local recurrence, and nodules and encasement should not be considered common post-operative infiltration. The role of the radiologist is essential to assess the predictive factors of recurrence and to identify early local recurrence. PMID- 26867910 TI - Common and uncommon pitfalls in pancreatic imaging: it is not always cancer. AB - Despite advances in multimodality imaging of pancreas, there is still overlap between imaging findings of several pancreatic/peripancreatic disease processes. Pancreatic and peripancreatic non-neoplastic entities may mimic primary pancreatic neoplasms on ultrasound, CT, and MRI. On the other hand, primary pancreatic cancer may be overlooked on imaging because of technical and inherent factors. The purpose of this pictorial review is to describe and illustrate pancreatic imaging pitfalls and highlight the basic radiological features for proper differential diagnosis. PMID- 26867911 TI - Impact of histologic subtype and sarcomatoid transformation on metastasis in renal cell carcinoma: a single institute experience in 149 patients. AB - PURPOSE: To compare the metastatic pattern and outcome of clear cell RCC (ccRCC) and papillary RCC (pRCC), and to assess the impact of sarcomatoid transformation on the disease spread and prognosis. MATERIALS AND METHODS: This IRB-approved, HIPAA-compliant retrospective study included 149 consecutive patients (108 men; mean age 58 years; range 25-86) with metastatic RCC (ccRCC = 116, pRCC = 33), identified from imaging database. All available imaging studies and electronic records of these patients were reviewed to document pathological features, distribution and timing of metastasis, and survival. The metastatic pattern and survival was first compared between the ccRCC and pRCC groups, and then between those with and without sarcomatoid transformation; all 27 cases of sarcomatoid transformation occurred in the ccRCC group. RESULTS: Metastases were noted at presentation in 62 (42%) and after median 13 months in the remaining 87 (58%) patients. Lymph nodes (134/149), lung (125/149), and bone (60/149) were the most common metastatic sites, which did not differ between the RCC subtypes. Pancreatic (p = 0.0014) and renal (p = 0.046) metastases were more common in ccRCC, lymphangitic spread (p = 0.0003) and peritoneal metastasis (p = 0.039) more common in pRCC. In ccRCC, sarcomatoid transformation was associated with high-grade tumors (p < 0.0001), more frequently demonstrated lymphangitic (p = 0.016), pleural (p = 0.0018), and peritoneal metastases (p = 0.0002), and had shorter metastasis-free survival and overall survival (log-rank test, p < 0.0001). In the absence of sarcomatoid transformation, ccRCC had longer metastasis-free interval (median 22 months compared to 6 months) (p = 0.0238) and overall survival (median survival 48 months vs. 25 months) (p = 0.0193) compared to pRCC. CONCLUSION: Histologic subtype, as well as the presence of sarcomatoid transformation, affects the metastatic pattern and metastasis-free survival of RCC. In the absence of sarcomatoid transformation, ccRCC has a better outcome than pRCC. PMID- 26867912 TI - Adrenal congestion preceding adrenal hemorrhage on CT imaging: a case series. AB - INTRODUCTION: Adrenal hemorrhage is an uncommon but potentially life-threatening condition, particularly in cases of bilateral adrenal hemorrhage causing primary adrenal insufficiency. It is difficult to diagnose clinically, particularly in critically ill patients, given its non-specific symptoms and signs, which include abdominal pain, vomiting, fever, weakness, hypotension, and altered conscious state. Non-traumatic adrenal hemorrhage has been observed to occur in times of physiological stress, such as post-surgery, sepsis, burns, and hypotension. This is hypothesized to be due to a combination of increased arterial blood flow to the adrenal glands, the paucity of draining adrenal venules and adrenal vein thrombosis, leading to intra-glandular vascular congestion and subsequent hemorrhage. CASE SERIES: We present four cases of non-traumatic adrenal hemorrhage, which demonstrated features of preceding adrenal congestion (adrenal gland thickening and peri-adrenal fat stranding) on computed tomography (CT) imaging. Comparison was made with 12 randomly selected intensive care patients to observe if these findings were prevalent in this subgroup of patients. CONCLUSION: Non-traumatic adrenal hemorrhage is an uncommon condition that is difficult to diagnose clinically. As such, it may be useful to recognize CT features of adrenal congestion as a sign for potential adrenal dysfunction and subsequent adrenal hemorrhage, so early steroid replacement therapy can be commenced to prevent death from adrenal insufficiency. PMID- 26867913 TI - Impact of hysterectomy on three-dimensional rectosigmoid morphology and endoscopy performance: a pilot study. AB - OBJECTIVES: Assess differences in three-dimensional colonic metrics on CTC in women with or without hysterectomy following incomplete endoscopy to determine if there is a correlation between colonic morphology and incomplete colonoscopy after hysterectomy. METHODS: Quantitative rectosigmoid metrics were derived from CTC datasets of 37 women with hysterectomy and 36 women without hysterectomy who underwent CTC for incomplete endoscopy. Evaluated metrics included colonic length, volume, tortuosity, and compactness and sigmoid apex height relative to the lumbosacral junction. Differences were measured using the Student's t test, and intra-reader reliability was assessed using ICC. The relative risk of incomplete rectosigmoid visualization was determined by reviewing the endoscopy reports. RESULTS: Women with hysterectomy had a lower sigmoid apex height (p = 0.002), as well as increased tortuosity (p = 0.012) and compactness (p = 0.001) and decreased length (p = 0.026) and volume (p = 0.016) of the rectosigmoid. Intra-reader reliability was high for centerline length (ICC = 0.9940) and sigmoid apex height (ICC = 0.9851). The relative risk of incomplete visualization of the rectosigmoid on endoscopy in women with hysterectomy was 2.068 (p = 0.043) compared to women without hysterectomy. CONCLUSION: Our pilot data show reproducible quantitative differences in three-dimensional metrics of the rectosigmoid in women with or without hysterectomy who underwent CTC for incomplete endoscopy and increased relative risk of incomplete endoscopic visualization of the rectosigmoid after hysterectomy. Our findings suggest that women with hysterectomy may benefit from CTC rather than endoscopy as the initial diagnostic test for evaluating the colon. PMID- 26867914 TI - Percutaneous biliary drainage effectively lowers serum bilirubin to permit chemotherapy treatment. AB - PURPOSE: For digestive tract cancers, the bilirubin threshold for administration of systemic chemotherapy can be 5 or 2 mg/dL (85.5 or 34.2 MUmol/L) depending upon the regimen. We examined the ability of percutaneous biliary drainage (PBD) in patients with malignant biliary obstruction to achieve these clinically relevant endpoints. METHODS: 106 consecutive patients with malignant biliary obstruction and a baseline serum bilirubin >2 mg/dL underwent PBD. Time to achieve a bilirubin of 5 mg/dL (85.5 MUmol/L), 2 mg/dL (34.2 MUmol/L), and survival was estimated by Kaplan-Meier analysis. Potential technical and clinical prognostic factors were subjected to univariate and multivariate analysis. Categorical variables were analyzed by the log rank test. Hazard ratios were calculated for continuous variables. RESULTS: Median survival was 100 days (range 1-3771 days). Among 88 patients with a pre-drainage bilirubin >5 mg/dL, 62% achieved a serum bilirubin <=5 mg/dL within 30 days and 84% within 60 days, median 21 days. Among 106 patients with a pre-drainage bilirubin >2 mg/dL, 37% achieved a serum bilirubin <=2 mg/dL by 30 days and 70% within 60 days, median 43 days. None of the technical or clinical factors evaluated, including pre-drainage bilirubin, were significant predictors of time to achieve a bilirubin <=2 mg/dL (p = 0.51). Size and type of biliary device were the only technical variables found to affect time to bilirubin of 5 mg/dL (p = 0.016). CONCLUSION: PBD of malignant obstruction achieves clinically relevant reduction in serum bilirubin in the majority of patients within 1-2 months, irrespective of the pre-drainage serum bilirubin, sufficient to allow administration of systemic chemotherapy. However, the decision to undergo this procedure for this indication alone must be considered in the context of patients' prognosis and treatment goals. PMID- 26867915 TI - Patient preferences for chaperone use during transvaginal sonography. AB - PURPOSE: To determine patient preferences for use of a chaperone during transvaginal sonography. MATERIALS AND METHODS: Informed consent was waived for this IRB-exempt, HIPAA-compliant, retrospective review of prospectively acquired quality improvement survey data. Willing unique consecutive adult patients (n = 155) scheduled to undergo a transvaginal pelvic ultrasound between March 1, 2015 and August 15, 2015 completed a survey before and after the ultrasound examination assessing their opinions regarding the need for a chaperone. Surveys were collected from three outpatient centers (n = 35/center) and an inpatient center (n = 50) in the same health system. Respondent opinions were compared with Chi-Square test or Fisher's Exact test. RESULTS: Most respondents (78% [121/155]) had previously undergone a transvaginal pelvic ultrasound. Respondents were significantly more likely to prefer a chaperone if their sonographer was male than if their sonographer was female (pre-ultrasound: 46% [69/155] vs. 12% [19/155], p < 0.0001; post-ultrasound: 43% [66/155] vs. 6% [10/155], p < 0.0001). The fraction of respondents who said they would be somewhat or substantially reassured by a chaperone if their sonographer was female was similar to the fraction of respondents who said they would be somewhat or substantially embarrassed by presence of a female chaperone (pre-ultrasound: 12% [19/155] vs. 6% [9/155], p = 0.07; post-ultrasound: 6% [10/155] vs. 7% [11/155], p = 0.82; respectively). CONCLUSION: Approximately half of adult women scheduled to undergo transvaginal pelvic sonography prefer that a chaperone be present if their sonographer is male, but in general do not feel it is necessary if their sonographer is female. These opinions do not change after performance of a transvaginal pelvic ultrasound. PMID- 26867916 TI - The "double bubble" sign. PMID- 26867917 TI - The "molar tooth" sign. PMID- 26867918 TI - The bullet on bodkin sign. PMID- 26867919 TI - The "Nubbin" Sign. PMID- 26867920 TI - The stained glass window appearance. PMID- 26867921 TI - 'Tardus-Parvus' waveform. PMID- 26867922 TI - Pictorial review of orthotopic neobladder reconstruction: indication, normal postsurgical anatomy, and complications. AB - Radical cystectomy with urinary diversion is a common urological procedure performed for the treatment of bladder cancer. Numerous surgical procedures have been developed for urinary diversion. Over the past decade, orthotopic neobladder reconstruction has been used frequently for urinary diversion because of its advantageousness in providing patients with a good quality of life compared with other urinary diversion technique. Knowledge of the indication, surgical procedure, and postsurgical anatomy of orthotopic neobladder reconstruction is essential. While the technique has many advantages, multiple postsurgical complications may occur after reconstruction, including urine leakage, bowel obstruction and fluid collection (lymphocele, urinoma, hematoma, and abscess), neobladder rupture, vesicoureteral reflux, hydronephrosis, urinary tract infection, urinary calculi, abdominal incisional hernia, bowel obstruction, intraneobladder tumor, and tumor recurrence. Radiological imaging including multiple modalities such as intravenous urography, cystography, CT, and MRI plays an important role in the postoperative evaluation of patients with orthotopic neobladder reconstruction and is an accurate method for evaluating complications. In addition, knowledge of appearances on multimodal imaging helps clinicians to select the modality required to achieve an accurate diagnosis of each complication and avoid misdiagnosis. PMID- 26867923 TI - Update on the imaging of malignant perivascular epithelioid cell tumors (PEComas). AB - Malignant perivascular epithelioid cell tumors (PEComas) are a histologic group of mesenchymal neoplasms that share a distinctive histological phenotype, the perivascular epithelioid cell. These tumors are known for their perivascular distribution. Malignant PEComas have a female predominance and are associated with aggressive disease and poor prognosis, making timely diagnosis critical to management. Imaging features of malignant PEComas are nonspecific and mimic other benign and malignant neoplasms. Surgery is the mainstay in the management of malignant PEComas. Promising novel molecular targeted therapies like m-TOR inhibitors have been shown to be effective in the metastatic setting. The aim of this review is to familiarize radiologists with the imaging appearances of and potential therapies for primary and metastatic malignant PEComa. PMID- 26867924 TI - Direct and indirect imaging features of adrenohepatic fusion. AB - It is difficult to make a correct diagnosis when a lesion arising from adrenohepatic fusion occurs. Also, the anatomical characteristics may lead to various radiological features so that it is frequent to under- or over-treat a lesion from adrenohepatic fusion. Adrenohepatic fusion is characterized by the close intermixture of hepatocytes and adrenocortical cells with rare or no formation of a peri-adrenal capsule. The purpose of this clinical perspective was to describe the direct and indirect imaging features of adrenohepatic fusion and show their clinical implications for patient care. PMID- 26867925 TI - The evaluation of abdominal findings in Crimean-Congo hemorrhagic fever. AB - OBJECTIVE: Crimean-Congo hemorrhagic fever (CCHF) is a widely seen, fatal disease and is endemic to some countries. It affects many organs in the abdomen. Comprehensive radiological study of CCHF is quite rare. This study will use multiple detector computed tomography (MDCT) to investigate if there is a relationship between clinical laboratory measurements and abdominal findings in CCHF and discuss our findings in the light of the literature. MATERIALS AND METHODS: We retrospectively evaluated the medical records of 443 patients diagnosed with CCHF in our hospital between April 1, 2008 and September 30, 2014. Fifty-one patients had undergone abdominal MDCT examination. RESULTS: The most common findings seen in abdominal MDCT were intra-abdominal free fluid and hepatomegaly. Gallbladder wall thickening, heterogeneity in mesenteric, omental fatty tissue, and splenomegaly were other common findings. Subcutaneous fat tissue edema, intramuscular hemorrhage, duodenal wall thickening, colon wall thickening, pancreatitis, and acute renal failure were among the rare findings seen in abdominal MDCT. Comparison of these findings to the clinical laboratory parameters showed a strong relationship between intra-abdominal free fluid and platelet count. CONCLUSION: Our study is the first comprehensive study on abdominal MDCT findings of CCHF. We detected a strong relationship between patients' platelet count and abdominal free liquid. Therefore, it should be kept in mind that abdominal free fluid can be among clinical manifestations in patients with platelet counts <=50000 and that this manifestation can become aggravated. PMID- 26867926 TI - Expression of peroxisome proliferator activation receptors (PPARs) and TNFalpha in placenta tissues in unexplained recurrent pregnancy loss: an immunohistochemical study. AB - INTRODUCTION: PPAR expression in placenta tissues regulates proinflammatory cytokine production and preserves the quiescence of the uterus during pregnancy. PPAR-gamma regulates inflammatory response during gestation while PPAR-delta and TNFalpha play a central role at implantation, decidualization and placentation. However, their expression levels affect normal pregnancy and may cause gestational complications and miscarriage. The aim of this report is to investigate the relationship of these molecules with unexplained recurrent miscarriage. MATERIALS-METHODS: The miscarriage group was obtained from 12 women, between the ages of 35 to 42 years, who miscarried during the 1st trimester of gestation and controls consisted of 12 healthy women, between the ages of 27 to 39 years, who had electively terminated their pregnancies, during the 1st trimester of gestation. The abortion material was processed and specimens taken were studied using immunohisto-chemical methods. Specimens were taken from decidua basalis and decidua parietalis. Monoclonal antibodies were used against PPAR-gamma (Peroxisome Proliferator Activation Receptor gamma), PPAR-delta and TNFalpha (Tumor Necrosis Factor alpha). The results were statistically analyzed with Mann-Whitney test. RESULTS: Our research identified PPAR-gamma expression in decidua basalis and decidua parietalis from control group and decidua basalis from miscarriage group. PPAR-delta expression was also identified in both deciduas from both groups. Statistically, no significant change in PPAR-gamma and PPAR-delta expression was observed between recurrent miscarriage group and controls. On the contrary, a statistically significant upregulation of TNFalpha was identified in both deciduas between miscarriage group and controls (p<0.05). CONCLUSIONS: Our evidence did not support a possible role of PPARs expression in recurrent pregnancy loss. However, a potential involvement of TNFalpha in the syndrome was reported. Further research should be performed due to insufficient bibliographic data. PMID- 26867927 TI - Radiofrequency ablation of posteroseptal accessory pathways associated with coronary sinus diverticula. AB - PURPOSE: Posteroseptal accessory pathways may be associated with a coronary sinus (CS) diverticulum. Our purpose was to describe the clinical characteristics, mapping and ablation of these pathways. METHODS: This was a retrospective study of all patients who underwent ablation of posteroseptal accessory pathways in a single centre. Patients with a diverticulum of the CS or one of its tributaries were included in group I, while the other patients formed group II. Clinical presentation, ablation procedure and outcome were compared between the two groups. RESULTS: A total of 51 patients were included, 16 in group I and 35 in group II. There were no significant differences in age or sex distribution. Atrial fibrillation (AF) and previous unsuccessful ablation were more common in group I. A negative delta wave in lead II was the ECG finding with best sensitivity and specificity for the presence of a diverticulum. A pathway potential was common at the successful site in group I, and the interval between local ventricular electrogram and delta wave onset was shorter (19.5 +/- 8 vs 33.1 +/- 7.6 ms, p < 0.001). There was a trend toward lower procedural success rate and higher recurrence rate in group I, although this was not significant. CONCLUSIONS: CS diverticula should be suspected in patients with manifest posteroseptal accessory pathways who have a previous failed ablation, documented AF or typical electrocardiographic signs. A discrete potential is frequently seen at the successful site, but the local ventricular electrogram is not as early as in other accessory pathways. PMID- 26867928 TI - When is enough, enough? Understanding and solving your sample size problems in health services research. AB - Health services researchers face two obstacles to sample size calculation: inaccessible, highly specialised or overly technical literature, and difficulty securing methodologists during the planning stages of research. The purpose of this article is to provide pragmatic sample size calculation guidance for researchers who are designing a health services study. We aimed to create a simplified and generalizable process for sample size calculation, by (1) summarising key factors and considerations in determining a sample size, (2) developing practical steps for researchers-illustrated by a case study and, (3) providing a list of resources to steer researchers to the next stage of their calculations. Health services researchers can use this guidance to improve their understanding of sample size calculation, and implement these steps in their research practice. PMID- 26867929 TI - A powerful score-based statistical test for group difference in weighted biological networks. AB - BACKGROUND: Complex disease is largely determined by a number of biomolecules interwoven into networks, rather than a single biomolecule. A key but inadequately addressed issue is how to test possible differences of the networks between two groups. Group-level comparison of network properties may shed light on underlying disease mechanisms and benefit the design of drug targets for complex diseases. We therefore proposed a powerful score-based statistic to detect group difference in weighted networks, which simultaneously capture the vertex changes and edge changes. RESULTS: Simulation studies indicated that the proposed network difference measure (NetDifM) was stable and outperformed other methods existed, under various sample sizes and network topology structure. One application to real data about GWAS of leprosy successfully identified the specific gene interaction network contributing to leprosy. For additional gene expression data of ovarian cancer, two candidate subnetworks, PI3K-AKT and Notch signaling pathways, were considered and identified respectively. CONCLUSIONS: The proposed method, accounting for the vertex changes and edge changes simultaneously, is valid and powerful to capture the group difference of biological networks. PMID- 26867932 TI - Shifting to settled cultivation: Changing practices among the Adis in Central Arunachal Pradesh, north-east India. AB - In the hilly tropics, although shifting cultivation is a widespread practice, government policies have attempted to replace it with other land uses. However, several factors determine whether farming communities can make the shift. We tried understanding the factors that facilitate or impede the shift to settled cultivation through interviews with the Adi tribe in north-east India. Although settled cultivation was initiated in the 60s, about 90 % of the families still practise shifting cultivation, observing 13 festivals associated with the annual agricultural calendar. Our results indicate that the economic status of a household determined whether a family undertook settled cultivation, while labour availability was important for shifting cultivation. Often, these nuances are ignored in the Government policies. We conclude that future policies should be mindful of cultural and socio-economic factors that affect the community and of the social-ecological resilience of the landscapes and not use a one-size-fits all strategy. PMID- 26867931 TI - Comparative immunogenicity and structural analysis of epitopes of different bacterial L-asparaginases. AB - BACKGROUND: E.coli type II L-asparaginase is widely used for treatment of acute lymphoblastic leukemia. However, serious side effects such as allergic or hypersensitivity reactions are common for L-asparaginase treatment. Methods for minimizing immune response on L-asparaginase treatment in human include bioengeneering of less immunogenic version of the enzyme or utilizing the homologous enzymes of different origin. To rationalize these approaches we compared immunogenicity of L-asparaginases from five bacterial organisms and performed sequence-structure analysis of the presumable epitope regions. METHODS: IgG and IgM immune response in C57B16 mice after immunization with Wollinella succinogenes type II (WsA), Yersinia pseudotuberculosis type II (YpA), Erwinia carotovora type II (EwA), and Rhodospirillum rubrum type I (RrA) and Escherichia coli type II (EcA) L-asparaginases was evaluated using standard ELISA method. The comparative bioinformatics analysis of structure and sequence of the bacterial L asparaginases presumable epitope regions was performed. RESULTS: We showed different immunogenic properties of five studied L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin as a second-line treatment. Studied L-asparaginases might be placed in the following order based on the immunogenicity level: YpA > RrA, WsA >= EwA > EcA. Most significant cross-immunogenicity was shown between EcA and YpA. We propose that a long N-terminus of YpA enzyme enriched with charged aminoacids and tryptophan could be a reason of higher immunogenicity of YpA in comparison with other considered enzymes. Although the recognized structural and sequence differences in putative epitope regions among five considered L-asparaginases does not fully explain experimental observation of the immunogenicity of the enzymes, the performed analysis set the foundation for further research in this direction. CONCLUSIONS: The performed studies showed different immunogenic properties of L-asparaginases and confirmed the possibility of replacement of EcA with L-asparaginase from different origin. The preferable enzymes for the second line treatment are WsA, RrA, or EwA. PMID- 26867930 TI - Do psychological and behavioral factors classified by the West Haven-Yale Multidimensional Pain Inventory (Swedish version) predict the early clinical course of low back pain in patients receiving chiropractic care? AB - BACKGROUND: To investigate if psychological and behavioral factors (as determined by the Swedish version of the West Haven-Yale Multidimensional Pain Inventory, MPI-S) can predict the early clinical course of Low Back Pain (LBP). METHODS: MPI S data from patients (18-65 years of age) seeking chiropractic care for recurrent and persistent LBP were collected at the 1(st) visit. A follow-up questionnaire was administered at the 4(th) visit. The predictive value of the MPI-S subgroups Adaptive Copers (AC), Interpersonally Distressed (ID) and Dysfunctional (DYS) was calculated against the subjective improvement at the 4(th) visit and clinically relevant difference in pain intensity between the 1(st) and 4(th) visit. RESULTS: Of the 666 subjects who were included at the 1(st) visit, 329 completed the questionnaire at the 4(th) visit. A total of 64.7 % (AC), 68.0 % (ID) and 71.3 % (DYS) reported a definite improvement. The chance of "definite improvement", expressed as relative risk (95 % CI) with the AC group as reference, was 1.05 (.87-1.27) for the ID and 1.10 (.93-1.31) for the DYS groups, respectively. The DYS and ID groups reported higher values in pain intensity both at the 1(st) and the 4(th) visit. The proportion of subjects who reported an improvement in pain intensity of 30 % or more (clinically relevant) were 63.5 % AC, 72.0 % ID and 63.2 % DYS. Expressed as relative risk (95 % CI) with the AC group as reference, this corresponded to 1.26 (.91-1.76) for the ID and 1.09 (.78-1.51) for the DYS groups, respectively. CONCLUSIONS: The MPI-S instrument could not predict the early clinical course of recurrent and persistent LBP in this sample of chiropractic patients. TRIAL REGISTRATION: Clinical trials.gov; NCT01539863 , February 22, 2012. PMID- 26867933 TI - Retrospective analysis of the influence of 25-hydroxyvitamin D on disease progression and survival in pancreatic cancer. AB - BACKGROUND: Vitamin D deficiency is implicated in neoplastic processes in multiple organs, including the pancreas. While animal and human data have established a relationship between serum vitamin D (25(OH)D) and the development of pancreatic cancer, few studies have examined the effects of 25(OH)D on time to progression (TTP) and overall survival (OS) in this patient population. We hypothesize that lower baseline serum concentrations (BSC) of 25(OH)D will be associated with decreased TTP and OS. METHODS: This retrospective analysis of 1222 patients with pancreatic cancer aims to identify potential relationships between 25(OH)D and both TTP and OS, while controlling for the effects of ethnicity and body mass index (BMI). Baseline 25(OH)D was divided into quartiles defined as deficient (<20 ng/mL), insufficient (20-39 ng/mL), sufficient (40-59 ng/mL), and optimal (>=60 ng/ml). Statistical significance was declared if the two-sided p-value was <= 0.05. RESULTS: For the 627 subjects included for analysis, the median 25(OH)D was 27 ng/mL (range 4 to 114), 30.0 % were 25(OH)D deficient (<20 ng/mL), and 47.2 % were insufficient (20-39 ng/mL). Ethnicity (p < 0.0001) and BMI (p = 0.05) were significantly associated with (BSC)of 25(OH)D, while TTP (p = 0.39) and OS (p = 0.37) were not associated. CONCLUSION: Suboptimal vitamin D levels (<60 ng/mL) occurred in 96 % of patients analyzed. Both ethnicity and BMI were statistically significantly associated with vitamin D deficiency and insufficiency. Similar to results previously reported in the literature, this analysis did not identify a significant association between BSC of 25(OH)D and OS or TTP in patients with pancreatic cancer. PMID- 26867935 TI - New Strategies in Breast Cancer: Immunotherapy. AB - More than 70% of breast cancers contain lymphocytic infiltration in the stroma, and preclinical studies suggest that immunoediting and partial control of cancer progression by the local immune microenvironment operate in most breast cancers. Consistent with this hypothesis, a large number of studies demonstrated a favorable prognostic and chemotherapy response predictive role for immune infiltration in breast cancer. The evidence is particularly strong for triple negative and HER2-positive cancers. The development of clinically effective immune checkpoint inhibitors now provides an opportunity to test the therapeutic potential of augmenting the local antitumor immune response. Several phase I clinical trials using single-agent anti-PD-1 and anti-PD-L1 antibodies demonstrated objective tumor response rates, with remarkably durable responses, in heavily pretreated, metastatic, triple-negative cancers and somewhat lower responses in estrogen receptor-positive cancers. Currently, close to 50 ongoing, or soon to open, clinical trials evaluate the role of this new treatment modality in breast cancer. Clin Cancer Res; 22(9); 2105-10. (c)2016 AACR. PMID- 26867936 TI - The Vertical Drop Jump Is a Poor Screening Test for ACL Injuries in Female Elite Soccer and Handball Players: A Prospective Cohort Study of 710 Athletes. AB - BACKGROUND: The evidence linking knee kinematics and kinetics during a vertical drop jump (VDJ) to anterior cruciate ligament (ACL) injury risk is restricted to a single small sample. Still, the VDJ test continues to be advocated for clinical screening purposes. PURPOSE: To test whether 5 selected kinematic and kinetic variables were associated with future ACL injuries in a large cohort of Norwegian female elite soccer and handball players. Furthermore, we wanted to assess whether the VDJ test can be recommended as a screening test to identify players with increased risk. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Elite female soccer and handball players participated in preseason screening tests from 2007 through 2014. The tests included marker-based 3-dimensional motion analysis of a drop-jump landing. We followed a predefined statistical protocol in which we included the following candidate risk factors in 5 separate logistic regression analyses, with new ACL injury as the outcome: (1) knee valgus angle at initial contact, (2) peak knee abduction moment, (3) peak knee flexion angle, (4) peak vertical ground-reaction force, and (5) medial knee displacement. RESULTS: A total of 782 players were tested (age, 21 +/- 4 years; height, 170 +/- 7 cm; body mass, 67 +/- 8 kg), of which 710 were included in the analyses. We registered 42 new noncontact ACL injuries, including 12 in previously ACL-injured players. Previous ACL injury (relative risk, 3.8; 95% CI, 2.1-7.1) and medial knee displacement (odds ratio, 1.40; 95% CI, 1.12-1.74 per 1-SD change) were associated with increased risk for injury. However, among the 643 players without previous injury, we found no association with medial knee displacement. A receiver operating characteristic curve analysis of medial knee displacement showed an area under the curve of 0.6, indicating a poor-to-failed combined sensitivity and specificity of the test, even when including previously injured players. CONCLUSION: Of the 5 risk factors considered, medial knee displacement was the only factor associated with increased risk for ACL. However, receiver operating characteristic curve analysis indicated a poor combined sensitivity and specificity when medial knee displacement was used as a screening test for predicting ACL injury. For players with no previous injury, none of the VDJ variables were associated with increased injury risk. CLINICAL RELEVANCE: VDJ tests cannot predict ACL injuries in female elite soccer and handball players. PMID- 26867937 TI - Integrating palliative care across settings: A retrospective cohort study of a hospice home care programme for cancer patients. AB - BACKGROUND: Terminally ill patients at the end-of-life do transit between care settings due to their complex care needs. Problems of care fragmentation could result in poor quality of care. AIM: We aimed to evaluate the impact of an integrated hospice home care programme on acute care service usage and on the share of home deaths. SETTINGS/PARTICIPANTS: The retrospective study cohort comprised patients who were diagnosed with cancer, had an expected prognosis of 1 year or less, and were referred to a home hospice. The intervention group comprised deceased patients enrolled in the integrated hospice home care programme between September 2012 and June 2014. The historical comparison group comprised deceased patients who were referred to other home hospices between January 2007 and January 2011. RESULTS: There were 321 cases and 593 comparator subjects. Relative to the comparator group, the share of hospital deaths was significantly lower for programme participants (12.1% versus 42.7%). After adjusting for differences at baseline, the intervention group had statistically significantly lower emergency department visits at 30 days (incidence rate ratio: 0.38; 95% confidence interval: 0.31-0.47), 60 days (incidence rate ratio: 0.61; 95% confidence interval: 0.54-0.69) and 90 days (incidence rate ratio: 0.69; 95% confidence interval: 0.62-0.77) prior to death. Similar results held for the number of hospitalisations at 30 days (incidence rate ratio: 0.48; 95% confidence interval: 0.40-0.58), 60 days (incidence rate ratio: 0.71; 95% confidence interval: 0.62-0.82) and 90 days (incidence rate ratio: 0.77; 95% confidence interval: 0.68-0.88) prior to death. CONCLUSION: Our results demonstrated that by integrating services between acute care and home hospice care, a reduction in acute care service usage could occur. PMID- 26867938 TI - Erratum to: SEOM guidelines for the treatment of gastric cancer 2015. PMID- 26867940 TI - Regioselective ortho-trifluoromethylthiolation of 2-arylbenzo[d]thiazole via tandem substrate-assisted C-H iodination and trifluoromethylthiolation. AB - A mild and efficient tandem benzo[d]thiazole directed C-H iodination and trifluoromethylthiolation for the synthesis of ortho-trifluoromethylthiolated 2 arylbenzo[d]thiazoles have been developed using AgSCF3 as a coupling partner. The reaction exhibits a diverse array of functional group tolerance giving the desired products in good to excellent yields. Regioselective trifluoromethylthiolation was observed at the less sterically hindered site when the phenyl ring of the substrate possesses a methyl group at its meta position. PMID- 26867939 TI - Classification, prevention and management of entero-atmospheric fistula: a state of-the-art review. AB - BACKGROUND: Entero-atmospheric fistula (EAF) is an enteric fistula occurring in the setting of an open abdomen, thus creating a communication between the GI tract and the external atmosphere. Management and nursing of patients suffering EAF carries several challenges, and prevention of EAF should be the first and best treatment option. PURPOSE: Here, we present a novel modified classification of EAF and review the current state of the art in its prevention and management including nutritional issues and feeding strategies. We also provide an overview on surgical management principles, highlighting several surgical techniques for dealing with EAF that have been reported in the literature throughout the years. CONCLUSIONS: The treatment strategy for EAF should be multidisciplinary and multifaceted. Surgical treatment is most often multistep and should be tailored to the single patient, based on the type and characteristics of the EAF, following its correct identification and classification. The specific experience of surgeons and nursing staff in the management of EAF could be enhanced, applying distinct simulation-based ex vivo training models. PMID- 26867941 TI - Non-targeted metabolite profiling reveals changes in oxidative stress, tryptophan and lipid metabolisms in fearful dogs. AB - BACKGROUND: Anxieties, such as shyness, noise phobia and separation anxiety, are common but poorly understood behavioural problems in domestic dogs, Canis familiaris. Although studies have demonstrated genetic and environmental contributions to anxiety pathogenesis, better understanding of the molecular underpinnings is needed to improve diagnostics, management and treatment plans. As a part of our ongoing canine anxiety genetics efforts, this study aimed to pilot a metabolomics approach in fearful and non-fearful dogs to identify candidate biomarkers for more objective phenotyping purposes and to refer to potential underlying biological problem. METHODS: We collected whole blood samples from 10 fearful and 10 non-fearful Great Danes and performed a liquid chromatography combined with mass spectrometry (LC-MS)-based non-targeted metabolite profiling. RESULTS: Non-targeted metabolomics analysis detected six 932 metabolite entities in four analytical modes [RP and HILIC; ESI(-) and ESI(+)], of which 239 differed statistically between the test groups. We identified changes in 13 metabolites (fold change ranging from 1.28 to 2.85) between fearful and non-fearful dogs, including hypoxanthine, indoxylsulfate and several phospholipids. These molecules are involved in oxidative stress, tryptophan and lipid metabolisms. CONCLUSIONS: We identified significant alterations in the metabolism of fearful dogs, and some of these changes appear relevant to anxiety also in other species. This pilot study demonstrates the feasibility of the non-targeted metabolomics and warrants a larger replication study to confirm the role of the identified biomarkers and pathways in canine anxiety. PMID- 26867943 TI - Corrigendum. AB - In the Research Article by Ozan Yazici, Nuriye Ozdemir, Ayse Ocak Duran, Serkan Menekse, Mehmet Ali Nahit Sendur, Halit Karaca, Gamze Goksel, Erkan Arpaci, Ilhan Hacibekiroglu, Irem Bilgetekin, Turgut Kacan, Metin Ozkan, Sercan Aksoy, Asude Aksoy, Suna Cokmert, Mukremin Uysal, Emin Tamer Elkiran, Irfan Cicin, Suleyman Buyukberber & Nurullah Zengin, titled 'The effect of the gastrectomy on survival in patients with metastatic gastric cancer: a study of ASMO', which appeared in the February 2016 issue of Future Oncology 12(3), 343-354 (2016), the following author name is presented incorrectly as: Mehmet Ali Nahit Sendur The correct presentation of this author name is: Mehmet Ali Sendur The authors and editors would like to sincerely apologize for any inconvenience or confusion this may have caused our readers. PMID- 26867942 TI - Highly Vascularized Primarily Inflammatory Pseudotumor of the Omentum in an Adult Male: A Case Report. AB - BACKGROUND: Inflammatory pseudotumors can affect any organ, whereas primary omental tumors are very rare. A few cases have been reported in the literature, all affecting adult patients. They are usually difficult to diagnose preoperatively and pathology remains the criterion standard for diagnosis. Surgical resection is considered the first-line treatment in limited disease, whereas recurrent or metastatic disease is treated by re-excision. There is no role for chemo- or radio-therapy in limited disease. Here, we present a rare case of omental myofibroblastic tumor in an adult male. CASE REPORT: A 38-year-old healthy man presented to our clinic complaining of lower abdominal pain associated with anorexia and low-grade fever, and he also reported weight loss. His initial hemoglobin was 9.7 g/dl. Magnetic resonance imaging (MRI) showed an enhancing solid mass in the lower abdomen, with close proximity to the appendix and the urinary bladder. The patient was treated successfully with laparotomy and excision of the tumor. Histopathology of the mass revealed spindle cells of vague fascicular pattern. Further immunohistochemical staining showed presence of reaction for CD68, CD34, and ALK. No omental infiltration was noted. No adjuvant treatment was applied and the patient was free of disease after 1-year follow-up. CONCLUSIONS: Omental pseudotumors are a rare pathology. They are usually slowly- growing, circumscribed tumors with a low malignant potential. They have a predilection for children. The overall mortality is reported to be 5-7% in cases with multiple recurrences. PMID- 26867944 TI - Ninth Triennial Toxicology Salary Survey. AB - This survey serves as the ninth in a series of toxicology salary surveys conducted at 3-year intervals and beginning in 1988. An electronic survey instrument was distributed to 5919 individuals including members of the Society of Toxicology, American College of Toxicology, and 23 additional professional organizations. Question items inquired about gender, age, degree, years of experience, certifications held, areas of specialization, society membership, employment and income. Overall, 1293 responses were received (response rate 21.8%). The results of the 2014 survey provide insight into the job market and career path for current and future toxicologists. PMID- 26867945 TI - Lenvatinib: A Review in Refractory Thyroid Cancer. AB - Lenvatinib (Lenvima(r)) is an oral, multi-targeted tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, fibroblast growth factor receptors 1, 2, 3 and 4, platelet-derived growth factor receptor alpha, and RET and KIT signalling networks, which are implicated in tumour growth and maintenance. In the EU and USA, lenvatinib is indicated for the treatment of locally recurrent or metastatic progressive, radioiodine-refractory differentiated thyroid cancer (RR-DTC). This approval was based on the results of the randomized, double-blind, multinational, phase 3 SELECT study, in which lenvatinib significantly improved median progression-free survival (PFS) and overall response rate compared with placebo in patients with RR-DTC. The PFS benefit with lenvatinib was seen in all pre-specified subgroups, including patients who had received either one or no prior VEGF-targeted therapy. Moreover, the PFS benefit with lenvatinib was maintained regardless of BRAF or RAS mutation status. The safety and tolerability profile of lenvatinib in SELECT was consistent with that of other VEGF/VEGF receptor-targeted therapies and was mostly manageable. Hypertension was the most common treatment-related adverse event in lenvatinib-treated patients, but only infrequently led to discontinuation of the drug. Although not collected in SELECT, information on quality of life would be useful in assessing the overall impact of therapy on the patient. This notwithstanding, the data which are available indicate that lenvatinib is an effective and generally well-tolerated treatment option for patients with RR-DTC. Lenvatinib, therefore, offers an acceptable alternative to sorafenib--currently, the only other TKI approved for this indication. PMID- 26867946 TI - Sonidegib: A Review in Locally Advanced Basal Cell Carcinoma. AB - Sonidegib (Odomzo(r)), an oral smoothened (SMO) antagonist, is indicated for the treatment of adults with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation therapy, or adults with recurrent laBCC following surgery or radiation therapy. In the multicentre BOLT trial, the primary endpoint (i.e., an objective tumour response rate point estimate of >=30 % and a 95 % confidence interval lower bound of >20 % in patients with fully assessable laBCC and all patients with metastatic BCC) was met at the primary analysis cut-off date (median follow-up 13.9 months) in the sonidegib 200 mg (36 % [95 % CI 24-50]) and 800 mg (34 % [95 % CI 25-43]) once-daily groups. Sonidegib 200 mg once daily (recommended dosage) had a better benefit-risk profile than the 800 mg dosage. Central review of the patients with laBCC in this population showed that 43 % achieved an objective response with sonidegib 200 mg once daily at the primary analysis date. Clinically meaningful responses were sustained in the sonidegib 200 mg group, based on an 18-month analysis. The majority of treatment-emergent adverse events were of mild to moderate severity and manageable with dosage adjustments, concomitant medications and/or non-drug therapies (e.g., adequate hydration). The acceptable benefit-risk profile of sonidegib, along with a paucity of treatment options and the seriousness of the condition, makes sonidegib an emerging option for the treatment of adults with laBCC that has recurred following surgery or radiation therapy, or in those who are not candidates for surgery or radiation therapy. PMID- 26867948 TI - The fabrication of formamidinium lead iodide perovskite thin films via organic cation exchange. AB - High-quality formamidinium lead iodide (FAPbI3) perovskite thin films are fabricated via organic cation exchange. With ammonia lead iodide (NH4PbI3) as the starting material, the NH4(+) in NH4PbI3 could be gradually substituted by FA(+) in formamidine acetate (FA-Ac) and simultaneously transformed to the pure phase alpha-FAPbI3 at elevated temperature. PMID- 26867947 TI - MAZ mediates the cross-talk between CT-1 and NOTCH1 signaling during gliogenesis. AB - Neurons and glia cells are differentiated from neural stem/progenitor cells (NSCs/NPCs) during brain development. Concomitant activation of JAK/STAT and NOTCH1 signaling is required for gliogenesis, a process to generate glia cells to ensure proper brain functions. NOTCH1 signaling is down-regulated during neurogenesis and up-regulated during gliogenesis. However, the underlying mechanism remains elusive. We report here that cardiotrophin-1 (CT-1) activates NOTCH1 signaling through the up-regulation of ADAM10, a rate-limiting factor of NOTCH1 signaling activation. We found that a transcriptional factor, Myc associated zinc finger protein (MAZ), plays an important role in ADAM10 transcription in response to CT-1 in NPCs. MAZ knockdown inhibits CT-1 stimulated gliogenesis and it can be rescued by over-expressing human NICD. Our results provide a link between NOTCH1 activation and neuronal secreted CT-1, suggesting that CT-1 plays an important role in ensuring the coordinated activation of NOTCH1 signaling during gliogenesis. PMID- 26867949 TI - The Nursing Home Compare Report Card: Perceptions of Residents and Caregivers Regarding Quality Ratings and Nursing Home Choice. AB - OBJECTIVE: To evaluate the perceived usefulness of publicly reported nursing home quality indicators. STUDY SETTING: Primary data were collected from October 2013 to August 2014 among a convenience sample of persons (or family member) recently admitted or anticipating admission to a nursing home within 75 miles of the city of Philadelphia. STUDY DESIGN: Structured interviews were conducted to assess the salience of data on the Medicare Nursing Home Compare website, including star ratings, clinical quality measures, and benchmarking of individual nursing home quality with state and national data. DATA COLLECTION: Interviews were transcribed verbatim, independently coded by two reviewers, and agreement determined. A thematic analysis of transcripts was undertaken. PRINCIPAL FINDINGS: Thirty-five interviews were completed. Eighty-three percent (n = 29) were caregivers and 17 percent (n = 6) were residents. Star ratings, clinical quality measures, and benchmarking information were salient to decision making, with preferred formats varying across participants. Participants desired additional information on the source of quality data. Confusion was evident regarding the relationship between domain-specific and overall star quality ratings. CONCLUSIONS: The Nursing Home Compare website provides salient content and formats for consumers. Increased awareness of this resource and clarity regarding the definition of measures could further support informed decision making regarding nursing home choice. PMID- 26867950 TI - Distribution of the type III DNA methyltransferases modA, modB and modD among Neisseria meningitidis genotypes: implications for gene regulation and virulence. AB - Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the 'hyperinvasive lineages' are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains. PMID- 26867952 TI - Characterizing colonic motility in children with chronic intractable constipation: a look beyond high-amplitude propagating sequences. AB - BACKGROUND: Children with chronic intractable constipation experience severe and long-lasting symptoms, which respond poorly to conventional therapeutic strategies. Detailed characterization of colonic motor patterns in such children has not yet been obtained. METHODS: In 18 children with chronic intractable constipation, a high-resolution water-perfused manometry catheter (36 sensors at 1.5-cm intervals) was colonoscopically placed with the tip at the distal transverse colon. Colonic motor patterns were recorded for 2 h prior to and after a meal and then after colonic infusion of bisacodyl. These data were compared with previously published colonic manometry data from 12 healthy adult controls and 14 adults with slow-transit constipation. KEY RESULTS: The postprandial number of the retrograde cyclic propagating motor pattern was significantly reduced in these children compared with healthy adults (children, 3.1 +/- 4.7/h vs healthy adults, 34.7 +/- 45.8/h; p < 0.0001) but not constipated adults (4.5 +/- 5.6/h; p = 0.9). The number of preprandial long-single motor patterns was significantly higher (p = 0.003) in children (8.0 +/- 13.2/h) than in healthy adults (0.4 +/- 0.9/h) and in constipated adults (0.4 +/- 0.7/h). Postprandial high-amplitude propagating sequences (HAPSs) were rarely observed in children (2/18), but HAPS could be induced by bisacodyl in 16 of 18 children. CONCLUSIONS & INFERENCES: Children with chronic intractable constipation show a similar impaired postprandial colonic response to that seen in adults with slow-transit constipation. Children may have attenuated extrinsic parasympathetic inputs to the colon associated with an increased incidence of spontaneous long-single motor patterns. PMID- 26867953 TI - Ultrasonic and mechanical soil washing processes for the removal of heavy metals from soils. AB - In order to determine the optimal operating conditions of full-scale soil washing processes for the removal of heavy metals, the effect of high-power ultrasound on the conventional mechanical soil washing process was investigated in a large lab scale 28kHz sonoreactor. The soil samples were obtained from an abandoned railway station site in Seoul, Korea, which was contaminated with Cu (242.7+/-40.0mg/kg), Pb (441.3+/-49.8mg/kg), and Zn (358.0+/-35.7mg/kg). The treated concentrations of three heavy metal species in each process were compared with the regulation levels. It was found that higher performance, satisfying the regulation levels, was obtained in the ultrasonic/mechanical process due to the combined effects of macroscale mixing and microscale sonophysical effects. Moreover ultrasound played a more important role in less favorable conditions for the mechanical washing process (less acidic or less washing liquid conditions). Considering the application of the ultrasonic/mechanical soil washing process in real contaminated sites, the optimal conditions for the reactor with the bottom area of 15*15cm2 and the input ultrasound power of 250W were determined as follows: (1) the amount of soil per an operation was a 300g; (2) the ratio of soil and liquid was 1:3; (3) the concentration of acidic washing liquid was 0.5M HCl. PMID- 26867951 TI - Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy. AB - Genomic safe harbors (GSHs) are sites in the genome able to accommodate the integration of new genetic material in a manner that ensures that the newly inserted genetic elements: (i) function predictably and (ii) do not cause alterations of the host genome posing a risk to the host cell or organism. GSHs are thus ideal sites for transgene insertion whose use can empower functional genetics studies in basic research and therapeutic applications in human gene therapy. Currently, no fully validated GSHs exist in the human genome. Here, we review our formerly proposed GSH criteria and discuss additional considerations on extending these criteria, on strategies for the identification and validation of GSHs, as well as future prospects on GSH targeting for therapeutic applications. In view of recent advances in genome biology, gene targeting technologies, and regenerative medicine, gene insertion into GSHs can potentially catalyze nearly all applications in human gene therapy. PMID- 26867954 TI - Toward a new paradigm for sonochemistry: Short review on nonequilibrium plasma observations by means of MBSL spectroscopy in aqueous solutions. AB - This review summarizes recent studies of multibubble sonoluminescence (MBSL) in aqueous media in order to highlight new insights into the origin of the sonochemical activity. The observation of OH(C2Sigma+-A2Sigma+) emission band and a spectroscopic analysis of OH(A2Sigma+-X2Pii) emission band in MBSL of water pre equilibrated with noble gases revealed the formation of a nonequilibrium plasma inside the collapsing bubble (Te>Tv>Tr, where Te is an electron temperature, Tv is a vibrational temperature and Tr is a rotational (gas) temperature). The Te and Tv estimated using OH(A2Sigma+-X2Pii) emission band increase with ultrasonic frequency. In Xe the Tv of OH(A2Sigma+) state is much higher than in Ar most probably due to the lower ionization potential of Xe. The MBSL of C2* Swan band (d3Pig-a3Piu) measured in aqueous tert-butanol (t-BuOH) solutions correlates with the data obtained for OH(A2Sigma+-X2Pii) emission band. Analysis of the gaseous products of t-BuOH sonolysis revealed a significant sonochemical activity even at high t-BuOH concentration when MBSL is totally quenched, indicating that drastic intrabubble conditions (plasma) are not necessarily accompanied by sonoluminescence. The nonequilibrium plasma model of cavitation allows to explain the reverse carbon isotope effect observed during the sonolysis of water in the presence of Ar/CO gas mixture. PMID- 26867956 TI - Peridischarge prophylactic platelet transfusions after stem cell transplant: is a tranfusion trigger needed? AB - BACKGROUND: We examined the appropriateness of prophylactic peridischarge platelet (PLT) transfusions and the feasibility of lowering the prophylactic PLT transfusion threshold in transplant recipients within 24 hours of discharge at a National Cancer Institute-designated comprehensive cancer center. STUDY DESIGN AND METHODS: From April 2011 to June 2014, each prophylactic PLT transfusion that was administered to transplant recipients within 24 hours of discharge was identified. Each transfusion was reviewed to identify the indication and to determine if the transfusion adhered to institutional guidelines. RESULTS: Of the 187 transplant patients identified, 44 patients received a prophylactic PLT transfusion within 24 hours of discharge. Of these 44 patients, transfusions were administered to fulfill a PLT count of 20 * 10(9) /L required for discharge (n = 25 patients), for the removal of a tunneled central venous catheter (n = 16 patients), for active bleeding (n = 1 patient), or due to active anticoagulation (n = 2 patients). CONCLUSIONS: The majority of PLT transfusions (95%) were appropriate, and only 5% were avoidable. If the prophylactic PLT transfusion threshold was decreased to 15 * 10(9) /L from 20 * 10(9) /L for central line removal and to fulfill discharge PLT count criteria, 41% of the currently appropriate PLT transfusions could have been avoided. These results suggest that a risk-adapted method to select autologous transplant recipients for prophylactic PLT transfusions may be beneficial. A future study is needed to address this issue. PMID- 26867955 TI - Cardio-metabolic risk factors in Argentine children. A comparative study. AB - Obesity and its complications are emerging in an epidemic manner in Latin American countries. AIMS: To estimate the prevalence of Cardio-Metabolic Risk Factors (CMRFs) and Metabolic Syndrome (MS) in overweight/obese (OW/OB) and normal weight (NW) adolescents and to examine the associated variables. MATERIAL AND METHODS: A cross-sectional comparative study was conducted in two groups of children, between 10 and 19 years of age, in seven Argentine provinces. A survey on dietary habits, physical activity, anthropometric and biochemical data was collected to identify CMRF and MS. The WHO definition adapted to children was used. RESULTS: 1009 children were assessed; 398 were male (39.4%), 601 (59.6%) were NW and 408 (40.4%) were OW/OB. The OW/OB had a significantly higher proportion of values defined as CMRF: 3.7% impaired fasting glucose >110mg/dl; 27.9% insulin >15 or 20MUU/l as they were pubertal/prepubertal; 53.2% Homeostatic Model Assessment (HOMA)>2.5; 45.6% High Density Lipoprotein (HDL)<40mg/dl; 37.7% TG>110mg/dl and 13.5% hypertension (SBP and/or diastolic Blood Pressure percentile >90). Prevalence of the MS in OW/OB patients was 40.3%. The MS was not observed in NW children. Significant differences were found for: family history of OW/OB, birth weight (BW), age at menarche, presence of acanthosis nigricans, waist circumference (WC) >90th percentile. The WC was positively correlated with BP, TG, insulin, HOMA and Body mass index Z score and negatively with HDL in the study population. CONCLUSIONS: We confirm obesity as a major determinant of CMRF and MS (40%), especially fat centralization. We stress the need to address obesity prevention plans in children and adolescents. PMID- 26867957 TI - MpUL-multi: Software for Calculation of Amyloid Fibril Mass per Unit Length from TB-TEM Images. AB - Structure determination for amyloid fibrils presents many challenges due to the high variability exhibited by fibrils and heterogeneous morphologies present, even in single samples. Mass per unit length (MPL) estimates can be used to differentiate amyloid fibril morphologies and provide orthogonal evidence for helical symmetry parameters determined by other methods. In addition, MPL data can provide insight on the arrangement of subunits in a fibril, especially for more complex fibrils assembled with multiple parallel copies of the asymmetric unit or multiple twisted protofilaments. By detecting only scattered electrons, which serve as a relative measure of total scattering, and therefore protein mass, dark field imaging gives an approximation of the total mass of protein present in any given length of fibril. When compared with a standard of known MPL, such as Tobacco Mosaic Virus (TMV), MPL of the fibrils in question can be determined. The program suite MpUL-multi was written for rapid semi-automated processing of TB-TEM dark field data acquired using this method. A graphical user interface allows for simple designation of fibrils and standards. A second program averages intensities from multiple TMV molecules for accurate standard determination, makes multiple measurements along a given fibril, and calculates the MPL. PMID- 26867958 TI - Induction of virulence factors in Giardia duodenalis independent of host attachment. AB - Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin, and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response. PMID- 26867959 TI - Two clonal types of human skin fibroblasts with different potentials for proliferation and tissue remodeling ability. AB - BACKGROUND: Skin fibroblast heterogeneity is of growing interest due to its relevance in not only skin development but also cutaneous wound healing. However, the characterization of human dermal fibroblasts at a clonal level has not been accomplished and their functional heterogeneity remains poorly understood. OBJECTIVE: The aim of this study was to define the clonal heterogeneity of human dermal fibroblasts. METHODS: Isolated human dermal fibroblasts were clonally expanded and categorized by comprehensive phenotypic and gene expression profiling. RESULTS: Single fibroblasts were significantly multiplied and efficiently cloned without chromosomal abnormalities under hypoxic conditions. Individual clones were heterogeneous in their proliferative capacity, and gene expression profiling revealed differences in the expression of genes involved in extracellular matrix synthesis and degradation. Each cloned fibroblast also had different abilities in terms of collagen remodeling. All phenotypic and gene expression data were analyzed with Spearman's rank correlation, and fibroblasts were categorized into at least two functional clonal types. One was highly proliferative, while the other was less proliferative but had the ability to remodel the tissue architecture. The proliferative clones were predominant in infants, but decreased with physiological aging. CONCLUSION: This study provides strong evidence for the functional heterogeneity of human dermal fibroblasts at a clonal level, which has implications regarding skin repair and aging. PMID- 26867960 TI - IL-33 down-regulates filaggrin expression by inducing STAT3 and ERK phosphorylation in human keratinocytes. PMID- 26867961 TI - A founder deletion of corneodesmosin gene is prevalent in Japanese patients with peeling skin disease: Identification of 2 new cases. PMID- 26867962 TI - Molecular characterization and antimicrobial susceptibility of tcdA-negative Clostridium difficile isolates from Guangzhou, China. AB - This study aimed to investigate the molecular characteristics and antimicrobial susceptibility of Clostridium difficile clinical isolates in Guangzhou, China. One hundred twenty isolates were collected from Guangzhou General Hospital at the Guangzhou Military Command in China from March 2014 to April 2015, and 9 isolates were identified as tcdA-negative/tcdB-positive (A(-)B(+)) strains. Results showed that all of the strains were confirmed to be ST37 and 0 single nucleotide variants (SNVs) were found in the PaLoc region, and >60 SNVs were identified throughout the whole genome sequence. The results show the diversity of the antibiotic and gene mutations present in these strains. All of the A(-)B(+) isolates were highly resistant to clindamycin and erythromycin; showed an average sensitivity to fluoroquinolones; and maintained a high susceptibility to metronidazole, vancomycin, and tigecycline. PMID- 26867963 TI - Higher recovery rate of microorganisms from cerebrospinal fluid samples by the BACTEC culture system in comparison with agar culture. AB - The aim of this study was to assess the diagnostic value of the BACTEC FX blood culture (BC) system as compared to the agar culture (AC) of cerebrospinal fluid samples (CSF), evaluating the recovery rate and the time to detection of microorganisms in a 3.5-year period. From December 2011 to May 2015, 1326 CSF samples (694 patients) were submitted to both AC and BC. Among the 150 positive samples (96 patients), 165 microorganisms were detected: 81 by both the protocols, 77 by BC alone, and 7 by AC alone, demonstrating a higher detection rate of BC (95.8%) than AC (53.3%). Although BC presents some disadvantages, it is able to improve the yield of clinically significant microorganisms, and it could potentially reduce the reporting time as compared to AC. The results obtained highlighted the necessity of a combined approach for the successful detection of central nervous system microbial infections. PMID- 26867964 TI - Investigation of a suspected nosocomial transmission of blaKPC3-mediated carbapenem-resistant Klebsiella pneumoniae by whole genome sequencing. AB - Whole genome sequencing (WGS) was compared to pulse-field gel electrophoresis (PFGE) of XbaI-digested genomic DNA, as methods by which to evaluate a potential transmission of carbapenem-resistant Klebsiella pneumoniae between 2 hospital inpatients. PFGE result demonstrated only 1-band difference between the isolates, suggesting probable relatedness. In contrast, while WGS data demonstrated the same sequence type and very similar chromosomal sequences, over 20 single nucleotide variants were identified between the isolates, bringing into question whether there was a transmission event. WGS also identified an additional plasmid, with an XbaI restriction site in the isolates of the second patient that was not identified by PFGE. While WGS provided additional information that was not available by PFGE, in this study, neither method could definitively conclude the relatedness between the isolates. PMID- 26867965 TI - Multidrug-resistant gram-negative bacilli colonization risk factors among trauma patients. AB - Prior studies have demonstrated high rates of colonization and infection with multidrug-resistant gram-negative bacilli (MDR-GNB) in injured military personnel. Our analysis shows that injuries inflicted during peak combat periods, massive blood transfusion requirement, and posttrauma cefazolin prophylaxis (additive effect with fluoroquinolones) were risk factors for MDR-GNB colonization. PMID- 26867966 TI - Rapid detection and typing of pathogenic nonpneumophila Legionella spp. isolates using a multiplex real-time PCR assay. AB - We developed a single tube multiplex real-time PCR assay that allows for the rapid detection and typing of 9 nonpneumophila Legionella spp. isolates that are clinically relevant. The multiplex assay is capable of simultaneously detecting and discriminating L. micdadei, L. bozemanii, L. dumoffii, L. longbeachae, L. feeleii, L. anisa, L. parisiensis, L. tucsonensis serogroup (sg) 1 and 3, and L. sainthelensis sg 1 and 2 isolates. Evaluation of the assay with nucleic acid from each of these species derived from both clinical and environmental isolates and typing strains demonstrated 100% sensitivity and 100% specificity when tested against 43 other Legionella spp. Typing of L. anisa, L. parisiensis, and L. tucsonensis sg 1 and 3 isolates was accomplished by developing a real-time PCR assay followed by high-resolution melt (HRM) analysis targeting the ssrA gene. Further typing of L. bozemanii, L. longbeachae, and L. feeleii isolates to the serogroup level was accomplished by developing a real-time PCR assay followed by HRM analysis targeting the mip gene. When used in conjunction with other currently available diagnostic tests, these assays may aid in rapidly identifying specific etiologies associated with Legionella outbreaks, clusters, sporadic cases, and potential environmental sources. PMID- 26867967 TI - Diagnostic accuracy of an IgM enzyme-linked immunosorbent assay and comparison with 2 polymerase chain reactions for early diagnosis of human leptospirosis. AB - Enzyme-linked immunosorbent assay (ELISA) tests and polymerase chain reaction (PCR) may play a key role for early detection and treatment of human leptospirosis in developing countries. The aims of this study were to develop and validate an IgM ELISA under field conditions and to compare the diagnostic accuracy among IgG, IgM ELISAs, conventional PCR (cPCR), and real-time PCR (rtPCR) for early detection of human leptospirosis. Overall accuracy of IgM ELISA was sensitivity of 87.9%, specificity of 97.0%, and area under the curve of 0.940. When the 4 methods were compared, IgM ELISA showed the greatest diagnostic accuracy (J=0.6) followed by rtPCR (J=0.4), cPCR (J=0.2) and IgG ELISA (J=0.1). Our results support the use of IgM ELISA and rtPCR for early diagnosis of the disease. Moreover, due to their high specificity, they could be also useful to replace or supplement microscopic agglutination test as a confirmatory test, allowing more confirmations. PMID- 26867968 TI - Cost-effectiveness assessment of lumpectomy cavity boost in elderly women with early stage estrogen receptor positive breast cancer receiving adjuvant radiotherapy. AB - BACKGROUND AND PURPOSE: Breast radiotherapy (RT) for elderly women with estrogen receptor positive early stage breast cancer (ER+ESBC) improves local recurrence (LR) rates without benefitting overall survival. Breast boost is a common practice, although the absolute benefit decreases with age. Consequently, an analysis of its cost-effectiveness in the elderly ESBC populations is warranted. MATERIAL AND METHODS: A Markov model was used to compare cost-effectiveness of RT with or without a boost in elderly ER+ESBC patients. The ten-year probability of LR with boost was derived from the CALGB 9343 trial and adjusted by the hazard ratio for LR from boost radiotherapy trial data, yielding the LR rate without boost. Remaining parameters were estimated using published data. RESULTS: Boost RT was associated with an increase in mean cost ($7139 vs $6193) and effectiveness (5.66 vs 5.64 quality adjusted life years; QALYs) relative to no boost. The incremental cost-effectiveness ratio (ICER) for boost was $55,903 per QALY. On one-way sensitivity analysis, boost remained cost-effective if the hazard ratio of LR with boost was <0.67. CONCLUSIONS: Boost RT for ER+ESBC patients was cost-effective over a wide range of assumptions and inputs over commonly accepted willingness-to pay-thresholds, but particularly in women at higher risk for LR. PMID- 26867970 TI - Knowledge, attitudes and decision-making preferences of men considering participation in the TROG RAVES Prostate Cancer Trial (TROG 08.03). AB - BACKGROUND AND PURPOSE: The RAVES (Trans-Tasman Radiation Oncology Group 08.03) randomised controlled trial (RCT), compares adjuvant radiotherapy with early salvage radiotherapy in men with high risk histopathological features at prostatectomy. The RAVES Decision Aid study evaluates the utility of a decision aid for men considering participation in the RAVES RCT. We report the RAVES Decision Aid study participants' attitudes and knowledge regarding RCTs, decision making preferences and decisional-conflict. MATERIALS AND METHODS: Baseline questionnaires assessed knowledge and attitudes towards RCTs and RAVES RCT. Sociodemographic and clinical predictors of knowledge were examined. Involvement in decision-making and difficulties with the decision-making process were assessed using validated tools. RESULTS: 127 men (median age=63years) were recruited through urologists (n=91) and radiation oncologists (n=36). Men preferred collaborative (35%) or semi-active (35%) decision-making roles. Most (>75%) felt the RAVES RCT was worthwhile and important with participation being wise. However, nearly half had high decisional-conflict regarding participation. Scores of objective knowledge regarding RCTs and RAVES RCT were low. CONCLUSIONS: Most men with high-risk histopathological features at prostatectomy desire active involvement in decision-making regarding further management. Despite positive attitudes towards RCTs and the RAVES RCT, there were gaps in knowledge and high decisional-conflict surrounding participation. PMID- 26867969 TI - Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation. AB - BACKGROUND: As proton beam radiation therapy (PBRT) may allow greater normal tissue sparing when compared with intensity-modulated radiation therapy (IMRT), we compared the dosimetry and treatment-related toxicities between patients treated to the ipsilateral head and neck with either PBRT or IMRT. METHODS: Between 01/2011 and 03/2014, 41 consecutive patients underwent ipsilateral irradiation for major salivary gland cancer or cutaneous squamous cell carcinoma. The availability of PBRT, during this period, resulted in an immediate shift in practice from IMRT to PBRT, without any change in target delineation. Acute toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty-three (56.1%) patients were treated with IMRT and 18 (43.9%) with PBRT. The groups were balanced in terms of baseline, treatment, and target volume characteristics. IMRT plans had a greater median maximum brainstem (29.7 Gy vs. 0.62 Gy (RBE), P < 0.001), maximum spinal cord (36.3 Gy vs. 1.88 Gy (RBE), P < 0.001), mean oral cavity (20.6 Gy vs. 0.94 Gy (RBE), P < 0.001), mean contralateral parotid (1.4 Gy vs. 0.0 Gy (RBE), P<0.001), and mean contralateral submandibular (4.1 Gy vs. 0.0 Gy (RBE), P < 0.001) dose when compared to PBRT plans. PBRT had significantly lower rates of grade 2 or greater acute dysgeusia (5.6% vs. 65.2%, P<0.001), mucositis (16.7% vs. 52.2%, P=0.019), and nausea (11.1% vs. 56.5%, P=0.003). CONCLUSIONS: The unique properties of PBRT allow greater normal tissue sparing without sacrificing target coverage when irradiating the ipsilateral head and neck. This dosimetric advantage seemingly translates into lower rates of acute treatment-related toxicity. PMID- 26867971 TI - De novo design of protein-protein interactions through modification of inter molecular helix-helix interface residues. AB - For de novo design of protein-protein interactions (PPIs), information on the shape and chemical complementarity of their interfaces is generally required. Recent advances in computational PPI design have allowed for de novo design of protein complexes, and several successful examples have been reported. In addition, a simple and easy-to-use approach has also been reported that arranges leucines on a solvent-accessible region of an alpha-helix and places charged residues around the leucine patch to induce interactions between the two helical peptides. For this study, we adopted this approach to de novo design a new PPI between the helical bundle proteins sulerythrin and LARFH. A non-polar patch was created on an alpha-helix of LARFH around which arginine residues were introduced to retain its solubility. The strongest interaction found was for the LARFH variant cysLARFH-IV-3L3R and the sulerythrin mutant 6L6D (KD=0.16 MUM). This artificial protein complex is maintained by hydrophobic and ionic interactions formed by the inter-molecular helical bundle structure. Therefore, by the simple and easy-to-use approach to create de novo interfaces on the alpha-helices, we successfully generated an artificial PPI. We also created a second LARFH variant with the non-polar patch surrounded by positively charged residues at each end. Upon mixing this LARFH variant with 6L6D, mesh-like fibrous nanostructures were observed by atomic force microscopy. Our method may, therefore, also be applicable to the de novo design of protein nanostructures. PMID- 26867972 TI - The synthesis, structural elucidation and antimicrobial activity of 2- and 4 substituted-coumarinyl chalcones. PMID- 26867974 TI - Nurses' role in medical error recovery: an integrative review. AB - AIMS AND OBJECTIVES: The aim of this study was to conduct an integrative review of the literature to fully understand nurses' role in medical error recovery. BACKGROUND: Despite focused efforts on error prevention, the prevalence of medical errors occurring in the health care system remains a concern. Patient harm can be reduced or prevented by adequate recovery processes that include identifying, interrupting and correcting medical errors in a timely fashion. Both medical error prevention and recovery are critical components in advancing patient safety, yet little is known about nurses' role in medical error recovery. DESIGN: An integrative review of the literature, guided by Whittmore and Knafl's (Journal of Advanced Nursing, 5, 2005, 546) five-step process, was conducted for the period between 2000-2015. A comprehensive search yielded twelve articles for this review. METHODS: The level and quality of evidence of the included articles was rated using a five-level rating system and the Johns Hopkins Nursing Quality of Evidence Appraisal developed by (c)The Johns Hopkins Hospital/The Johns Hopkins University. RESULTS: The medical error recovery rate varied across specialty nursing populations with nurses recovering, on average, as many as one error per shift to as few as one error per week. Nurses rely on knowing the patient, environment and plan of care to aid in medical error recovery. CONCLUSIONS: Nurses play a unique yet invisible role in identifying, interrupting and recovering medical errors. Individual and organisational factors influencing nurses' ability to recover medical errors remain unclear. RELEVANCE TO CLINICAL PRACTICE: Greater understanding of nurse characteristics and organisational factors that influence error recovery can foster the development of effective strategies to detect and correct medical errors and enable organisations to reduce negative outcomes. PMID- 26867973 TI - Plasma EGFR T790M ctDNA status is associated with clinical outcome in advanced NSCLC patients with acquired EGFR-TKI resistance. AB - EGFR T790M mutation occurs in half of non-small cell lung cancer (NSCLC) patients with acquired EGFR-TKI (TKI) resistance, based on tumor re-biopsies using an invasive clinical procedure. Here, we dynamically monitored T790M mutation in circulating tumor DNA (ctDNA) using serial plasma samples from NSCLC patients receiving TKI through Droplet Digital PCR (ddPCR) method and the associations between overall survival (OS) starting from initial TKI treatment and the T790M ctDNA status detected in plasma were analyzed. Among 318 patients, 117 who acquired TKI resistance were eligible for the analysis. T790M ctDNA was detected in the plasma of 55/117 (47%) patients. Almost half of the T790M ctDNA positive patients were identified at a median time of 2.2 months prior to clinically progressive disease (PD). Furthermore, within the patients receiving TKI treatment at 2(nd) line or later, the T790M ctDNA positive group had significantly shorter OS than the negative group (median OS: 26.9 months versus NA, P = 0.0489). Our study demonstrates the feasibility of monitoring EGFR mutation dynamics in serial plasma samples from NSCLC patients receiving TKI therapy. T790M ctDNA can be detected in plasma before and after PD as a poor prognostic factor. PMID- 26867975 TI - Corrigendum: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. PMID- 26867976 TI - The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K(+) Solution. AB - In 80-90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K(+) solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K(+) is extremely controversial, this study provides information for the understanding of different G quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K(+) solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design. PMID- 26867978 TI - Peloruside A: a lead non-taxoid-site microtubule-stabilizing agent with potential activity against cancer, neurodegeneration, and autoimmune disease. AB - Covering: 2000 up to 2016Peloruside A, a macrocyclic secondary metabolite from a New Zealand marine sponge, Mycale hentscheli, has shown potent antiproliferative activity in cultured cancer cells as well as inhibitory effects on tumor growth in mouse models. The compound also has promising effects against cell models of neurodegenerative and autoimmune diseases. In mechanistic studies, peloruside A shares with paclitaxel (Taxol(r)) the ability to stabilize microtubules by binding to beta-tubulin. Peloruside A, however, occupies a unique external site on beta-tubulin that does not overlap the classical taxoid site that is located on the inside of the microtubule. As such, peloruside A has been of central importance in defining a new microtubule-stabilizer binding site localized on the exterior surface of the microtubule that has led to increased interest in the design of an upscaled total synthesis of the natural product and its analogues. Here, we review advances in the biochemical and biological validation of peloruside A as an attractive therapeutic candidate for the treatment of cancer, neurodegeneration, and autoimmune disease. PMID- 26867977 TI - Hypoxia-mediated autophagic flux inhibits silver nanoparticle-triggered apoptosis in human lung cancer cells. AB - Solid tumors are frequently associated with resistance to chemotherapy because the fraction of hypoxic tumor cells is substantial. To understand the underlying mechanism of hypoxia on silver nanoparticle (AgNPs)-induced apoptosis, the expression of hypoxia-inducible factor (HIF)-1alpha, a hallmark of hypoxia, was measured in the presence and absence of AgNPs. The results showed that HIF-1alpha expression was upregulated after AgNPs treatment under both hypoxic and normoxic conditions. Cell viability assays showed that AgNPs promoted cell death in cancer cells but not in non-cancer cells, as cancer cells are slightly more acidic than normal cells. However, reactive oxygen species generation induced by AgNPs in lung cancer cells caused high susceptibility to oxidative stress, whereas pre exposure to hypoxia blocked AgNPs-induced oxidative stress. Notably, HIF-1alpha inhibited AgNPs-induced mitochondria-mediated apoptosis by regulating autophagic flux through the regulation of ATG5, LC3-II, and p62. Further, cell viability after treatment of cancer cells with AgNPs under hypoxic conditions was lower in HIF-1alpha siRNA-transfected cells than in control siRNA-transfected cells, indicating that HIF-1alpha knockdown enhances hypoxia induced decrease in cell viability. Our results suggest that hypoxia-mediated autophagy may be a mechanism for the resistance of AgNPs-induced apoptosis and that strategies targeting HIF 1alpha may be used for cancer therapy. PMID- 26867979 TI - Definition of a safe zone for antegrade lag screw fixation of fracture of posterior column of the acetabulum by 3D technology. AB - The objective of this study was to define a safe zone for antegrade lag screw fixation of fracture of posterior column of the acetabulum using a novel 3D technology. Pelvic CT data of 59 human subjects were obtained to reconstruct three-dimensional (3D) models. The transparency of 3D models was then downgraded along the axial perspective (the view perpendicular to the cross section of the posterior column axis) to find the largest translucent area. The outline of the largest translucent area was drawn on the iliac fossa. The line segments of OA, AB, OC, CD, the angles of OAB and OCD that delineate the safe zone (ABDC) were precisely measured. The resultant line segments OA, AB, OC, CD, and angles OAB and OCD were 28.46mm(13.15-44.97mm), 45.89mm (34.21-62.85mm), 36.34mm (18.68 55.56mm), 53.08mm (38.72-75.79mm), 37.44 degrees (24.32-54.96 degrees ) and 55.78 degrees (43.97-79.35 degrees ) respectively. This study demonstrates that computer-assisted 3D modelling techniques can aid in the precise definition of the safe zone for antegrade insertion of posterior column lag screws. A full length lag screw can be inserted into the zone (ABDC), permitting a larger operational error. PMID- 26867980 TI - Countering a multi-faceted terrorist wave through an integrated emergency-care system. PMID- 26867981 TI - Kendrick's extrication device and unstable pelvic fractures: Should a trochanteric belt be added? A cadaveric study. AB - INTRODUCTION: Pre-hospital pelvic stabilisation is advised to prevent exsanguination in patients with unstable pelvic fractures (UPFs). Kendrick's extrication device (KED) is commonly used to extricate patients from cars or crevasses. However the KED has not been tested for potential adverse effects in patients with pelvic fractures. The aim of this study was to examine the effect of the KED on pubic symphysis diastasis (SyD) with and without the use of a trochanteric belt (TB) during the extraction process following a MVC. MATERIALS AND METHODS: Left-sided "open-book" UPFs were created in 18 human cadavers that were placed in seven different positions simulating pre-extraction and extraction positions using the KED with and without a TB in two different positions (through and over the thigh straps). The SyD was measured using anteroposterior radiographs. The effects of the KED with and without TB, on the SyD, were evaluated. RESULTS: The KED alone resulted in a non-significant increase of the SyD compared to baseline, whereas the addition of a TB to the KED resulted in a significant reduction of the SyD (p<0.001). The TB through the straps provided a significantly better reduction than the TB over the straps in the extracted position (p<0.05). CONCLUSION: Our study demonstrated that a TB in combination with the KED on UPFs is an effective way to achieve early reduction. The addition of the TB in combination with the KED could be considered for Pre-Hospital Trauma Life Support (PHTLS) training protocols. PMID- 26867982 TI - A 4 year prospective longitudinal study of progression of dental erosion associated to lifestyle in 13-14 year-old Swedish adolescents. AB - OBJECTIVES: To evaluate the progression of dental erosion in 13-14 year-olds after 4 years, and its association with lifestyle and oral health. METHODS: 227 randomly selected 13-14 year-olds from a Public Dental Clinic, Orebro, Sweden, were investigated. A clinical examination was performed which included dental caries/gingival/plaque status, as well as grading of dental erosion at the tooth surface and participant levels in "marker teeth", including buccal/palatal surfaces of 6 maxillary anterior teeth (13-23), and occlusal surfaces of first molars. An interview and a questionnaire regarding drinking habits and other lifestyle factors were completed. All investigations were repeated at follow-up. The participants were divided into high and low progression erosion groups and logistic regression statistics were applied. RESULTS: 175 individuals participated at follow-up. Progression occurred in 35% of the 2566 tooth surfaces. 32% of the surfaces had deteriorated by one severity grade (n=51 individuals) and 3% by two grades (n=2 individuals). Boys showed more severe erosion than girls at the follow-up. Among the variables predicting greater progression, a lower severity of erosive wear at baseline had the highest OR (13.3), followed in descending order by a "retaining" drinking technique, more frequent intake of drinks between meals, low GBI and lesser sour milk intake, with reference to the baseline recording. Using these five variables, sensitivity and specificity were 87% and 67% respectively, for predicting progression of erosion. CONCLUSIONS: Progression of erosive lesions in Swedish adolescents aged 13-14 years followed up to age 17-18 years was common and related to certain lifestyle factors. CLINICAL SIGNIFICANCE: In permanent teeth, dental erosion may develop early in life and its progression is common. Dental health workers should be made aware of this fact and regular screenings for erosion and recording of associated lifestyle factors should be performed. PMID- 26867983 TI - Radiosensitisation of human colorectal cancer cells by ruthenium(II) arene anticancer complexes. AB - Some of the largest improvements in clinical outcomes for patients with solid cancers observed over the past 3 decades have been from concurrent treatment with chemotherapy and radiotherapy (RT). The lethal effects of RT on cancer cells arise primarily from damage to DNA. Ruthenium (Ru) is a transition metal of the platinum group, with potentially less toxicity than platinum drugs. We postulated that ruthenium-arene complexes are radiosensitisers when used in combination with RT. We screened 14 ruthenium-arene complexes and identified AH54 and AH63 as supra-additive radiosensitisers by clonogenic survival assays and isobologram analyses. Both complexes displayed facial chirality. At clinically relevant doses of RT, radiosensitisation of cancer cells by AH54 and AH63 was p53-dependent. Radiation enhancement ratios for 5-10 micromolar drug concentrations ranged from 1.19 to 1.82. In p53-wildtype cells, both drugs induced significant G2 cell cycle arrest and apoptosis. Colorectal cancer cells deficient in DNA damage repair proteins, EME1 and MUS81, were significantly more sensitive to both agents. Both drugs were active in cancer cell lines displaying acquired resistance to oxaliplatin or cisplatin. Our findings broaden the potential scope for these drugs for use in cancer therapy, including combination with radiotherapy to treat colorectal cancer. PMID- 26867984 TI - Progress in treatments for colorectal cancer peritoneal metastases during the years 2010-2015. A systematic review. AB - Peritoneal metastases (PM) from colorectal cancer (CRC) were traditionally associated with bad prognosis. Only recently, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in survival improvements. A systematic literature search between January 2010 and June 2015 was performed. Studies were selected and appraised according to predetermined criteria. Nineteen cohort studies, and thirteen comparative studies of CRS/HIPEC were included. The weighted median overall survival was 31.6 months (range 16 51). Major morbidity was 17.6-52.4% (weighted average 32.6%). Mortality was 0 8.1% (weighted average 2.9%). Additional relevant topics, such as CRC-PM prevalence, results by systemic therapies, preoperative work-up, and technical aspects were summarized through a narrative review. The recent literature suggests that CRS/HIPEC is gaining acceptance as standard of care for selected CRC-PM patients. Refinement of selection criteria, and rationalization of comprehensive systemic and local-regional management is ongoing. Prevention and early treatment of PM are new and promising options. PMID- 26867985 TI - Ether-linked lipids of Dermabacter hominis, a human skin actinobacterium. AB - Dermabacter hominis is a medically important actinobacterial inhabitant of human skin, although it is rarely implicated in infections. The lipid composition of D. hominis is revisited in this study in the context of its natural resistance to daptomycin, an antibiotic whose activity is influenced by membrane lipids. Thin layer chromatography and mass spectrometry revealed that this species contains phospholipids and glycolipids. Using electrospray ionization time of flight mass spectrometry (exact mass) and gas chromatography-mass spectrometry, the major phospholipid of D. hominis was identified as plasmanyl-phosphatidylglycerol (pPG), because it presented one alkyl chain and one acyl chain in the glycerol moiety of the molecule. The structure of the major glycolipid (GL1) was studied by combined gas-liquid chromatography, mass spectrometry and nuclear magnetic resonance, and was established as galactosyl-alpha-(1->2)-glucosyl-alkyl-acyl glycerol. Lipid analyses showed differences between one daptomycin-resistant (DAP R) strain and one daptomycin-sensitive (DAP-S) strain growing in the presence of the antibiotic: DAP-R tended to accumulate GL1 and to reduce pPG, whereas DAP-S maintained high proportions of pPG. The results demonstrate the existence of ether-linked lipids in D. hominis and reveal a differential distribution of phospholipids and glycolipids according to the sensitivity or resistance to daptomycin, although the mechanism(s) operating in the resistance to the antibiotic remain(s) to be elucidated. PMID- 26867986 TI - Self-Assembly of Telechelic Tyrosine End-Capped PEO and Poly(alanine) Polymers in Aqueous Solution. AB - The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(L-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into beta sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers--in particular the Tyr5-PEO6k Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide-polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5 PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped "associative polymers". Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-groups. PMID- 26867987 TI - Portal annular pancreas: An unusual pancreatic anomaly. PMID- 26867989 TI - Epidemiology and outcomes of squamous ovarian carcinoma; a population-based study. AB - OBJECTIVE: Squamous ovarian carcinoma (SOC) is a rare tumor. Scarcity of information about the epidemiology and prognosis of SOC hinders attempts at optimal patient management. This retrospective study of a large cohort details the clinicopathological and demographic characteristics and prognosis of women with SOC. METHODS: A cohort of patients drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database who were diagnosed with SOC between 1988 and 2012 were analyzed. Observed and disease specific survival was estimated by Kaplan-Meier plots in women who underwent surgery as part of their cancer-related treatment. A Cox hazard regression analysis was performed to determine independent predictors of cancer-specific survival in patients with SOC. RESULTS: We identified 341 patients with SOC with a median age at diagnosis of 55 years. Stage I, II, III and IV tumors were noted in 34%, 15%, 20.5% and 24.9% of patients, respectively. Five-year cancer-specific survival was 86% for stage I, 54.3% for stage II, 36.3% for stage III and 2.8% for stage IV disease patients. Observed and cancer-specific survival was better for patients that underwent lymphadenectomy (p=0.031). Postoperative radiotherapy was not associated with improved survival. In a multivariate analysis, independent predictors of improved cancer-specific survival were younger age, lower disease stage and lymphadenectomy. CONCLUSIONS: SOC is typically a unilateral malignancy with a tendency toward loco-regional spread. Stage I patients have a relatively high survival rate; however, the prognosis is poor for women with abdominal or distant spread. Lymphadenectomy, but not postoperative radiotherapy, is associated with improved survival. PMID- 26867990 TI - On-Surface Synthesis of Atomically Precise Graphene Nanoribbons. AB - The surface-assisted polymerization and cyclodehydrogenation of specifically designed organic precursors provides a route toward atomically precise graphene nanoribbons, which promises to combine the outstanding electronic properties of graphene with a bandgap that is sufficiently large for room-temperature digital logic applications. Starting from the basic concepts behind the on-surface synthesis approach, this report covers the progress made in understanding the different reaction steps, in synthesizing atomically precise graphene nanoribbons of various widths and edge structures, and in characterizing their properties, ending with an outlook on the challenges that still lie ahead. PMID- 26867988 TI - Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. AB - BACKGROUND: Ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists (NMDAR antagonists) recently demonstrated antidepressant efficacy for the treatment of refractory depression, but effect sizes, trajectories and possible class effects are unclear. METHOD: We searched PubMed/PsycINFO/Web of Science/clinicaltrials.gov until 25 August 2015. Parallel-group or cross-over randomized controlled trials (RCTs) comparing single intravenous infusion of ketamine or a non-ketamine NMDAR antagonist v. placebo/pseudo-placebo in patients with major depressive disorder (MDD) and/or bipolar depression (BD) were included in the analyses. Hedges' g and risk ratios and their 95% confidence intervals (CIs) were calculated using a random-effects model. The primary outcome was depressive symptom change. Secondary outcomes included response, remission, all cause discontinuation and adverse effects. RESULTS: A total of 14 RCTs (nine ketamine studies: n = 234; five non-ketamine NMDAR antagonist studies: n = 354; MDD = 554, BD = 34), lasting 10.0 +/- 8.8 days, were meta-analysed. Ketamine reduced depression significantly more than placebo/pseudo-placebo beginning at 40 min, peaking at day 1 (Hedges' g = -1.00, 95% CI -1.28 to -0.73, p < 0.001), and loosing superiority by days 10-12. Non-ketamine NMDAR antagonists were superior to placebo only on days 5-8 (Hedges' g = -0.37, 95% CI -0.66 to -0.09, p = 0.01). Compared with placebo/pseudo-placebo, ketamine led to significantly greater response (40 min to day 7) and remission (80 min to days 3-5). Non-ketamine NMDAR antagonists achieved greater response at day 2 and days 3-5. All-cause discontinuation was similar between ketamine (p = 0.34) or non-ketamine NMDAR antagonists (p = 0.94) and placebo. Although some adverse effects were more common with ketamine/NMDAR antagonists than placebo, these were transient and clinically insignificant. CONCLUSIONS: A single infusion of ketamine, but less so of non-ketamine NMDAR antagonists, has ultra-rapid efficacy for MDD and BD, lasting for up to 1 week. Development of easy-to-administer, repeatedly given NMDAR antagonists without risk of brain toxicity is of critical importance. PMID- 26867991 TI - Ethylene vinyl alcohol copolymer (Onyx((r))) embolization of cranial dural arteriovenous fistula via the ascending pharyngeal artery. PMID- 26867998 TI - Photodynamic UVA-riboflavin bacterial elimination in antibiotic-resistant bacteria. AB - BACKGROUND: To evaluate the bactericidal effect of clinical ultraviolet A (UVA) settings used in photoactivated chromophore for infectious keratitis (PACK) collagen cross-linking (CXL) in antibiotic-resistant and non-resistant bacterial strains. METHODS: Well-characterized bacterial strains from clinical isolates, without and with antibiotic resistance, were studied in a pairwise comparison. The evaluated pathogens were Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. Bacteria were dispersed in PBS and diluted to a concentration of approximately 4 * 105 /ml. Riboflavin was added to a concentration of 0.01%. By spreading the solution on a microscope slide, a fluid film layer, with a thickness of around 400 mm, was formed and UVA exposure followed. Eight separate exposures were made for each strain (n = 8). The degree of elimination in resistant and non-resistant pathogens was compared. RESULTS: The bactericidal efficacy of exposure differed between the tested microorganisms, and the mean elimination ranged between 60 and 92%, being most extensive in both of the evaluated Pseudomonas strains and least in the E. faecalis strains. Similar reductions were seen in antibiotic-resistant and non-resistant strains, with the exception of S. aureus, in which the resistant strain metchicillin resistant Staphylococcus aureus (MRSA) was eradicated in a greater extent than the non-resistant strain (P = 0.030). CONCLUSION: UVA-riboflavin settings used in PACK-CXL are effective in reducing both antibiotic-resistant and non-resistant bacteria. Antibiotic resistance does not appear to be protective against the photooxidative exposure. PMID- 26867999 TI - Celebrate a Bad Day. PMID- 26868000 TI - The protein phosphatase 6 catalytic subunit (Ppp6c) is indispensable for proper post-implantation embryogenesis. AB - Ppp6c, which encodes the catalytic subunit of phosphoprotein phosphatase 6 (PP6), is conserved among eukaryotes from yeast to humans. In mammalian cells, PP6 targets IkappaBepsilon for degradation, activates DNA-dependent protein kinase to trigger DNA repair, and is reportedly required for normal mitosis. Recently, Ppp6c mutations were identified as candidate drivers of melanoma and skin cancer. Nonetheless, little is known about the physiological role of Ppp6c. To investigate this function in vivo, we established mice lacking the Ppp6c phosphatase domain by crossing heterozygous mutants. No viable homozygous pups were born, indicative of a lethal mutation. Ppp6c homozygous mutant embryos were identified among blastocysts, which exhibited a normal appearance, but embryos degenerated by E7.5 and showed clear developmental defects at E8.5, suggesting that mutant embryos die after implantation. Accordingly, homozygous blastocysts showed significant growth failure of the inner cell mass (ICM) in in vitro blastocyst culture, and primary Ppp6c exon4-deficient MEFs showed greatly reduced proliferation. These results establish for the first time that the Ppp6c phosphatase domain is indispensable for mouse embryogenesis after implantation. PMID- 26868002 TI - Rhizobacter profundi sp. nov., isolated from freshwater sediment. AB - Three bacterial strains, designated DS48-6-5T, DS48-6-7 and DS48-6-9, were isolated from a sediment sample taken from Daechung Reservoir (Republic of Korea) at a water depth of 48 m. Cells of the strains were Gram-stain-negative, aerobic, rod-shaped and motile with a single polar flagellum. Comparative 16S rRNA gene sequence studies showed that the three isolates had clear affiliation with Betaproteobacteria and the closest relatives were Rhizobacter bergeniae KCTC 32299T, Rhizobacter dauci DSM 11587T and Rhizobacter fulvus KCTC 12591T with 97.2 97.9 % 16S rRNA gene sequence similarities; the 16S rRNA gene sequence similarities between the three strains were 99.5-100 %. The only isoprenoid quinone of the three strains was ubiquinone-8, and the major fatty acids were summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and C16 : 0. The G+C content of the genomic DNA of strains DS48-6-5T, DS48-6-7 and DS48-6-9 was 66.7, 67.0 and 66.8 mol%, respectively. DNA-DNA hybridization values of the novel strains with R. bergeniae KCTC 32299T, R. dauci DSM 11587T and R. fulvus KCTC 12591T were 19.3-48.5 %. Based on the evidence from this taxonomic study using a polyphasic approach, it is proposed that strains, DS48-6-5T, DS48-6-7 and DS48-6 9, represent a novel species of the genus Rhizobacter, for which the name Rhizobacter profundi sp. nov. is proposed. The type strain is DS48-6-5T ( = KCTC 42645T = NBRC 111169T). PMID- 26868001 TI - Expression profile of the sex determination gene doublesex in a gynandromorph of bumblebee, Bombus ignitus. AB - Gynandromorphy that has both male and female features is known in many insect orders, including Hymenoptera. In most cases, however, only external morphology and behavioral aspects have been studied. We found a gynandromorph of bumblebee, Bombus ignitus, that showed almost bilateral distribution of external sexual traits, with male characters observed on the left side and female characters on the right side. This individual never exhibited sexual behavior toward new queens. The dissection of the head part showed that it had bilaterally dimorphic labial glands, only the left of which was well developed and synthesized male specific pheromone components. In contrast, the gynandromorph possessed an ovipositor and a pair of ovaries in the abdominal part, suggesting that it had a uniformly female reproductive system. Furthermore, we characterized several internal organs of the gynandromorph by a molecular biological approach. The expression analyses of a sex determination gene, doublesex, in the brain, the fat bodies, the hindgut, and the ovaries of the gynandromorph revealed a male-type expression pattern exclusively in the left brain hemisphere and consistent female type expression in other tissues. These findings clearly indicate the sexual discordance between external traits and internal organs in the gynandromorph. The results of genetic analyses using microsatellite markers suggested that this individual consisted of both genetically male- and female-type tissues. PMID- 26868003 TI - Resting State fMRI Demonstrates a Disturbance of the Cerebello-Cortical Circuit in Essential Tremor. AB - Individuals with essential tremor (ET) have postural and active movement abnormalities. Disturbances in the cerebello-thalamo-cortical circuit may contribute to the several motor symptoms of ET. Resting state fMRI provides a valuable, noninvasive tool to study intrinsic activation in the human brain, particularly in the brains of individuals with neuropsychiatric diseases. To investigate the low frequency oscillation features of intrinsic activation in ET in this study, we performed a resting state fMRI analysis in 24 patients with ET and 23 healthy controls. The amplitudes of low frequency fluctuation (ALFF) were analyzed. When compared with healthy controls, patients showed significantly enhanced ALFF in the bilateral cerebral cortex, which is related to motor function, including the pre- and post-central gyrus, supplementary motor area and paracentral lobule. The larger ALFF value in the right precentral gyrus is related to a longer duration of tremor. The decreased ALFF in the bilateral cerebellum was also observed in patients. In addition, aberrant ALFF in the right cerebellar tonsil was negatively associated with the duration of tremor. Our findings suggest that abnormalities exist in the intrinsic activation of brain regions in patients with ET. These findings provide noninvasive evidence that supports the hypothesis that the abnormality of intrinsic activity in the cerebello-cerebral cortex pathway could be associated with the motor-related symptoms of ET. Furthermore, the duration of a tremor might relate to the severity of the alterations to the motor system of ET. PMID- 26868004 TI - On the Differentiation of Foveal and Peripheral Early Visual Evoked Potentials. AB - The C1 is one of the earliest visual evoked potentials observed following the onset of a patterned stimulus. The polarity of its peak is dependent on whether stimuli are presented in the upper or lower regions of the peripheral visual field, but has been argued to be negative for stimuli presented to the fovea. However, there has yet to be a systematic investigation into the extent to which the peripheral C1 (pC1) and foveal C1 (fC1) can be differentiated on the basis of response characteristics to different stimuli. The current study employed checkerboard patterns (Exp 1) and sinusoidal gratings of different spatial frequency (Exp 2) presented to the fovea or within one of the four quadrants of the peripheral visual field. The checkerboard stimuli yielded a sizable difference in peak component latency, with the fC1 peaking ~32 ms after the pC1. Further, the pC1 showed a band-pass response magnitude profile that peaked at 4 cycles per degree (cpd), whereas the fC1 was high-pass for spatial frequency, with a cut-off around 4 cpd. Finally, the scalp topographies of the pC1 and fC1 in both experiments differed greatly, with the fC1 being more posterior than the pC1. The results reported here call into question recent attempts to characterize general C1 processes without regard to whether stimuli are placed in the fovea or in the periphery. PMID- 26868005 TI - Intravitreal aflibercept for choroidal neovascularization in ocular sarcoidosis. AB - PURPOSE: To report a case of choroidal neovascularization (CNV) in a patient with ocular sarcoidosis treated by intravitreal aflibercept. METHODS: A 27-year old man was referred to our department because of sudden visual acuity decrease (best corrected visual acuity (BCVA) was 20/80 LE). Fundus examination showed bilateral optic disk swelling, retinal pigment epithelium changes at the posterior pole, yellowish chorioretinal lesions in the periphery, and the presence of a prominent peripapillary neovascular complex. RESULTS: The clinical diagnosis was most compatible with ocular sarcoidosis, later confirmed by mediastinal lymph node biopsy. Fluorescein and indocyanine green angiography confirmed the presence of active peripapillary type 2 (classic) CNV in both eyes. Given that the exudation of the peripapillary CNV harmed the fovea, the patient underwent a single intravitreal aflibercept injection LE. One month after the treatment, LE BCVA decreased to 20/125. Spectral-domain optical coherence tomography (SD-OCT) showed complete resolution of subretinal fluid but revealed outer retinal atrophy with complete loss of the ellipsoid zone (EZ) in the macula (possibly responsible for visual acuity worsening). Six months later, LE BCVA slightly increased to 20/100, and SD-OCT showed partial recovery of the EZ in the macula. No adverse events related to the treatment were recorded during follow-up. CONCLUSIONS: We report a case of CNV in a patient with ocular sarcoidosis treated with intravitreal aflibercept. In our experience, intravitreal aflibercept injection achieved morphologic resolution for sarcoid-related peripapillary CNV. PMID- 26868006 TI - Adherence to European Society for Cataract and Refractive Surgery recommendations among Italian cataract surgeons: a survey. AB - PURPOSE: To survey the surgical routines with regards to prophylactic strategies in a sample of Italian hospitals and compare these with European Society for Cataract and Refractive Surgery (ESCRS) guidelines. METHODS: Six private and 18 public hospitals were included in this clinical-based retrospective study. The overall volume of cataract operations in the 24 centers in 2013 was 43,553. Main outcome measure was incidence of endophthalmitis per 1,000. An incidence of less than 0.13% was considered acceptable. RESULTS: Our study provides the first Italian data on the use of intracameral antibiotics in cataract surgery as recommended by the ESCRS. Thirteen centers (54%) used intracameral cefuroxime at the end of surgery. Of the 13 centers that used cefuroxime, 8 (62%) had an incidence of endophthalmitis less than 0.13%. Of the 7 (29%) centers that did not use intracameral cefuroxime, all had an endophthalmitis rate of greater than 0.13%. This difference was statistically significant (p<0.05). Among the 4 centers not included, 2 used vancomycin in the infusion bottle, 1 a fluoroquinolone, and the last a combination of antibiotics. The majority of surgeons (71%) used preoperative antibiotic eyedrops, but this measure was not shown to be significantly protective. CONCLUSIONS: Slightly more than half of the centers surveyed in this study adhered to the recommendations of the ESCRS and routinely employed prophylactic intracameral cefuroxime. An incidence of endophthalmitis greater than 0.13% was encountered significantly more frequently among centers that did not employ intracameral cefuroxime. PMID- 26868007 TI - Visual and anatomic outcomes after conversion to aflibercept in neovascular age related macular degeneration: 12-month results. AB - PURPOSE: To investigate 12-month outcomes of conversion to aflibercept in patients with neovascular age-related macular degeneration resistant to ranibizumab. METHODS: Twenty-two eyes of 19 consecutive patients received 3 monthly aflibercept injections followed by a pro re nata protocol. Spectral domain optical coherence tomography (OCT) images were obtained before each injection. All 49 cross-sectional OCT B-scans obtained in each examination were investigated and the largest choroidal neovascularization (CNV) size was chosen. The same cross-sectional B-scan sections containing the maximum CNV size were used during the follow-up. RESULTS: After 12 months, best-corrected visual acuity increased from 45.68 +/- 20.25 to 59.09 +/- 17.50 Early Treatment Diabetic Retinopathy Study letters (p<0.001), central subfield thickness decreased from 399.91 +/- 148.85 to 304.55 +/- 97.89 MUm (p = 0.003), area of CNV declined from 0.38 +/- 0.24 to 0.28 +/- 0.19 mm2 (p = 0.003), and macular volume improved from 9.64 +/- 1.75 to 8.45 +/- 0.98 mm3 (p<0.001). There was a significant resolution of intraretinal fluid (p = 0.016), but reduction of subretinal fluid was not significant (p = 0.25). CONCLUSIONS: Visual and anatomic improvement were obtained after conversion to aflibercept. PMID- 26868008 TI - Selecting Fuchs patients for drug trials involving endothelial cell proliferation. AB - PURPOSE: Fuchs endothelial corneal dystrophy (FECD) might be managed by drug treatment before becoming severe enough to require surgery. For a clinical trial of such a drug, we hypothesize that selecting an adequate number of patients with FECD with only moderately compromised cell densities will be challenging. Thus, the purpose of the present study was to measure the prevalence of patients with FECD exhibiting moderately decreased corneal cell densities. METHODS: A retrospective data mining study (cross-sectional study) was performed on patient charts presenting at a large US northwestern academic health center by searching for diagnosis ICD-9 code 371.57 and Fuchs corneal dystrophies, including those with prior cataract surgeries and/or existing glaucoma. Patients with prior corneal transplants were excluded. Noncontact specular photomicroscopic data (Topcon 2000) were obtained from the central region whenever possible, and individual eyes were grouped according to cell density (cells/mm2): severe (<800), moderate (800-1,500), and mild (>1,500). RESULTS: The values for 98 eyes from 61 patients with FECD were as follows (mean +/- SD): corneal thickness 573 +/- 59 MUm, cell size 627 +/- 336 MUm2/cell, coefficient of variation 23 +/- 7, and density 1,883 +/- 703 cells/mm2. The moderate subgroup with cell density values averaging 1,184 +/- 212 (26) comprised 27% of the total FECD patient pool. CONCLUSIONS: Only approximately 1 out of 4 patients with FECD will show moderately compromised corneal cell densities. A moderate level of damage may be optimal for clinical trials for testing topical drugs on endothelial cell viability. Thus, investigators will need to initially screen a fourfold excess of all patients with FECD. PMID- 26868009 TI - INTERNAL DOSES OF THREE PERSONS STAYING 110 KM SOUTH OF THE FUKUSHIMA DAIICHI NUCLEAR POWER STATION DURING THE ARRIVAL OF RADIOACTIVE PLUMES BASED ON DIRECT MEASUREMENTS. AB - The authors describe the results of direct measurements made on three persons who stayed in Tokai-mura, a village located ~110 km south of the Fukushima Daiichi Nuclear Power Station (FDNPS), during the arrival of significant radioactive plumes released from the FDNPS as a consequence of the Tohoku earthquake/tsunami/FDNPS accident in March 2011. These measurements were made using a NaI(Tl) spectrometer and a whole-body counter shortly after the accident. Their thyroid equivalent doses ((131)I) were estimated to be 0.9-1.4 mSv under the assumption of acute intake via inhalation on 15 March, when the first significant release event was observed. Although greatly depending on the physicochemical form of iodine, the intake amount ratios of (131)I to (137)Cs for the three subjects were calculated as 2.7-3.7, which were much smaller than the radioactivity ratio (7.8) found in air sampling at the same site. PMID- 26868010 TI - HOW DO HOSPITAL STERILISATION PROCEDURES AFFECT THE RESPONSE OF PERSONAL EXTREMITY RINGS AND OF EYE LENS TL DOSEMETERS? AB - Stringent standards of hygiene must be applied in medical institutions, especially at operating blocks or during interventional radiology procedures. Medical equipment, including personal dosemeters that have to be worn by medical staff during such procedures, needs therefore to be sterilised. In this study, the effect of various sterilisation procedures has been tested on the dose response of extremity rings and of eye lens dosemeters in which thermoluminescent (TL) detectors (of types MTS-N and MCP-N, respectively) are used. The effects of medical sterilisation procedures were studied: by chemicals, by steam or by ultraviolet (UV), on the dose assessment by extremity rings and by eye lens dosemeters. Since it often happens that a dosemeter is accidentally machine washed together with protective clothing, the effect of laundering on dose assessment by these dosemeters was also tested. The sterilisation by chemicals is mostly safe for TL detectors assuming that the dosemeters are waterproofed. Following sterilisation by water vapour, the response of these dosemeters diminished by some 30 %, irrespectively of the period of sterilisation; therefore, this method is not recommended. UV sterilisation can be applied to EYE DTM eye lens dosemeters if their encapsulation is in black. The accidental dosemeter laundry in a washing machine has no impact on measured dose. PMID- 26868011 TI - NUMERICAL SIMULATION OF DIRECT MEASUREMENT TO DETERMINE THYROID 131I CONTENT OF TWO TEPCO WORKERS CONSIDERING INDIVIDUAL TISSUE THICKNESS. AB - After the Fukushima Daiichi Nuclear Power Station accident, the National Institute of Radiological Sciences examined seven heavily exposed emergency workers and performed internal dose estimations. The largest dose contributor was found to be (131)I, which was detected by thyroid monitor with an HPGe detector. Different energy peaks from (131)I were simultaneously identified in the pulse height spectra of the two subjects with the highest doses regardless of late measurements. A closer look at the spectra indicated that the count ratio of the two peak areas at 80.2 and 365 keV differed somewhat between the individual workers, suggesting a difference in attenuation in the overlaying soft tissue and in the thyroid itself. In this study, the relationship between the count ratio (80.2/365 keV) and the thickness of soft tissue overlying the thyroid was investigated by means of numerical simulations performed using the Japanese Male (JM) phantom varying the thickness of the overlaying tissue. From the measured count ratios, it was possible to estimate that the overlaying tissue was thinner for Worker 1 (difference from the JM phantom: -0.34+/-1.29 cm) and thicker for Worker 2 (diff.: 2.5+/-1.2 cm). The thyroid (131)I contents evaluated taking into account the individual thicknesses were 4.3 kBq for Worker 1 and 8.4 kBq for Worker 2, resulting in a significant increase for Worker 2 compared with the content based on the default counting efficiency at 365 keV of the original JM phantom. However, the results have large uncertainty factors of 1.4 for Worker 1 and 1.3 for Worker 2 and should be carefully considered together with other factors influencing the attenuation. PMID- 26868012 TI - THORACIC SPINE IMAGING: A COMPARISON BETWEEN RADIOGRAPHY AND TOMOSYNTHESIS USING VISUAL GRADING CHARACTERISTICS. AB - The aim of the present study was to evaluate digital tomosynthesis (DTS) in thoracic spine imaging, comparing the reproduction of anatomical structures with that achieved using digital radiography (DR). In a prospective visual grading study, 23 patients referred in 2014 for elective radiographic examination of the thoracic spine were examined using lateral DR and DTS. The DR image and the DTS section images were read in random order by four radiologists, evaluating the ability of the modalities to present a clear reproduction of nine specific relevant structures of the thoracic vertebrae 3, 6 and 9 (T3, T6 and T9). The data were analysed using visual grading characteristics (VGC) analysis. The VGC analysis revealed a statistically significant difference in favour of DTS for all evaluated structures, except for the anterior vertebral edges and lower end plate surfaces of T6 and T9 and the cancellous bone of T9. The difference was most striking in T3 and for posterior structures. For no structure in any vertebra was the reproduction rated significantly better for DR. In conclusion, DTS of the thoracic spine appears to be a promising alternative to DR, especially in areas where the problem of overlaying anatomy is accentuated, such as posterior and upper thoracic structures. PMID- 26868014 TI - Molecular epidemiological tracing of a cattle rabies outbreak lasting less than a month in Rio Grande do Sul in southern Brazil. AB - BACKGROUND: Vampire bat-transmitted cattle rabies cases are typically encountered in areas where the disease is endemic. However, over the period of a month in 2009, an outbreak of cattle rabies occurred and then ended spontaneously in a small area of the Rio Grande do Sul State in southern Brazil. To investigate the epidemiological characteristics of this rabies outbreak in Rio Grande do Sul, 26 nucleotide sequences of rabies virus (RABV) genomes that were collected in this area were analyzed phylogenetically. RESULTS: Nucleotide sequence identities of the nucleoprotein gene and G-L intergenic region of the 26 RABVs were greater than 99.6 %. Phylogenetic analysis showed that all RABVs clustered with the vampire bat-related cattle RABV strains and that the RABVs were mainly distributed in southern Brazil. CONCLUSIONS: The findings of the present study suggested that a small population of rabid vampire bats carrying a single RABV strain produced a spatiotemporally restricted outbreak of cattle rabies in southern Brazil. PMID- 26868015 TI - Evaluation of focal cartilage lesions of the knee using MRI T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC). AB - BACKGROUND: Assessment of degenerative changes of the cartilage is important in knee cartilage repair surgery. Magnetic Resonance Imaging (MRI) T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) are able to detect early degenerative changes. The hypothesis of the study was that cartilage surrounding a focal cartilage lesion in the knee does not possess degenerative changes. METHODS: Twenty-eight consecutive patients included in a randomized controlled trial on cartilage repair were evaluated using MRI T2 mapping and dGEMRIC before cartilage treatment was initiated. Inclusion was based on disabling knee problems (Lysholm score of <= 75) due to an arthroscopically verified focal femoral condyle cartilage lesion. Furthermore, no major malalignments or knee ligament injuries were accepted. Mean patient age was 33 +/- 9.6 years, and the mean duration of knee symptoms was 49 +/- 60 months. The MRI T2 mapping and the dGEMRIC measurements were performed at three standardized regions of interest (ROIs) at the medial and lateral femoral condyle, avoiding the cartilage lesion RESULTS: The MRI T2 mapping of the cartilage did not demonstrate significant differences between condyles with or without cartilage lesions. The dGEMRIC results did not show significantly lower values of the affected condyle compared with the opposite condyle and the contra-lateral knee in any of the ROIs. The intraclass correlation coefficient (ICC) of the dGEMRIC readings was 0.882. CONCLUSION: The MRI T2 mapping and the dGEMRIC confirmed the arthroscopic findings that normal articular cartilage surrounded the cartilage lesion, reflecting normal variation in articular cartilage quality. STUDY IDENTIFIER: NCT00885729 , registered April 17 2009. PMID- 26868013 TI - Physiological roles of the mitochondrial permeability transition pore. AB - Neurons experience high metabolic demand during such processes as synaptic vesicle recycling, membrane potential maintenance and Ca2+ exchange/extrusion. The energy needs of these events are met in large part by mitochondrial production of ATP through the process of oxidative phosphorylation. The job of ATP production by the mitochondria is performed by the F1FO ATP synthase, a multi protein enzyme that contains a membrane-inserted portion, an extra-membranous enzymatic portion and an extensive regulatory complex. Although required for ATP production by mitochondria, recent findings have confirmed that the membrane confined portion of the c-subunit of the ATP synthase also houses a large conductance uncoupling channel, the mitochondrial permeability transition pore (mPTP), the persistent opening of which produces osmotic dysregulation of the inner mitochondrial membrane, uncoupling of oxidative phosphorylation and cell death. Recent advances in understanding the molecular components of mPTP and its regulatory mechanisms have determined that decreased uncoupling occurs in states of enhanced mitochondrial efficiency; relative closure of mPTP therefore contributes to cellular functions as diverse as cardiac development and synaptic efficacy. PMID- 26868016 TI - Erratum to: Weakly supervised learning of biomedical information extraction from curated data. PMID- 26868019 TI - Erratum to: Integrating traditional indigenous medicine and western biomedicine into health systems: a review of Nicaraguan health policies and miskitu health services. PMID- 26868017 TI - Distinct genomic and epigenomic features demarcate hypomethylated blocks in colon cancer. AB - BACKGROUND: Large mega base-pair genomic regions show robust alterations in DNA methylation levels in multiple cancers. A vast majority of these regions are hypomethylated in cancers. These regions are generally enriched for CpG islands, Lamin Associated Domains and Large organized chromatin lysine modification domains, and are associated with stochastic variability in gene expression. Given the size and consistency of hypomethylated blocks (HMB) across cancer types, we hypothesized that the immediate causes of methylation instability are likely to be encoded in the genomic region near HMB boundaries, in terms of specific genomic or epigenomic signatures. However, a detailed characterization of the HMB boundaries has not been reported. METHOD: Here, we focused on ~13 k HMBs, encompassing approximately half of the genome, identified in colon cancer. We modeled the genomic features of HMB boundaries by Random Forest to identify their salient features, in terms of transcription factor (TF) binding motifs. Additionally we analyzed various epigenomic marks, and chromatin structural features of HMB boundaries relative to the non-HMB genomic regions. RESULT: We found that the classical promoter epigenomic mark--H3K4me3, is highly enriched at HMB boundaries, as are CTCF bound sites. HMB boundaries harbor distinct combinations of TF motifs. Our Random Forest model based on TF motifs can accurately distinguish boundaries not only from regions inside and outside HMBs, but surprisingly, from active promoters as well. Interestingly, the distinguishing TFs and their interacting proteins are involved in chromatin modification. Finally, HMB boundaries significantly coincide with the boundaries of Topologically Associating Domains of the chromatin. CONCLUSION: Our analyses suggest that the overall architecture of HMBs is guided by pre-existing chromatin architecture, and are associated with aberrant activity of promoter-like sequences at the boundary. PMID- 26868020 TI - 3-Component synthesis of alpha-substituted sulfonamides via Bronsted acid catalyzed C(sp(3))-H bond functionalization of 2-alkylazaarenes. AB - A Bronsted acid-catalyzed addition of 2-alkylazaarenes to in situ generated N sulfonylimines through selective C(sp(3))-H bond functionalization has been developed. This protocol provides an atom- and step-economic approach to alpha substituted sulfonamides. PMID- 26868021 TI - Welfare changes could put an extra 1.5 million children into poverty. PMID- 26868018 TI - Exercise and Environmental Enrichment as Enablers of Task-Specific Neuroplasticity and Stroke Recovery. AB - Improved stroke care has resulted in greater survival, but >50% of patients have chronic disabilities and 33% are institutionalized. While stroke rehabilitation is helpful, recovery is limited and the most significant gains occur in the first 2-3 months. Stroke triggers an early wave of gene and protein changes, many of which are potentially beneficial for recovery. It is likely that these molecular changes are what subserve spontaneous recovery. Two interventions, aerobic exercise and environmental enrichment, have pleiotropic actions that influence many of the same molecular changes associated with stroke injury and subsequent spontaneous recovery. Enrichment paradigms have been used for decades in adult and neonatal animal models of brain injury and are now being adapted for use in the clinic. Aerobic exercise enhances motor recovery and helps reduce depression after stroke. While exercise attenuates many of the signs associated with normal aging (e.g., hippocampal atrophy), its ability to reverse cognitive impairments subsequent to stroke is less evident. It may be that stroke, like other diseases such as cancer, needs to use multimodal treatments that augment complimentary neurorestorative processes. PMID- 26868022 TI - Identification of Molecular Targets for Predicting Colon Adenocarcinoma. AB - BACKGROUND Colon adenocarcinoma mostly happens at the junction of the rectum and is a common gastrointestinal malignancy. Accumulated evidence has indicated that colon adenocarcinoma develops by genetic alterations and is a complicated disease. The aim of this study was to screen differentially expressed miRNAs (DEMs) and genes with diagnostic and prognostic potentials in colon adenocarcinoma. MATERIAL AND METHODS In this study we screened DEMs and their target genes (DEGs) between 100 colon adenocarcinoma and normal samples in The Cancer Genome Atlas (TCGA) database by using the DEseq toolkit in Bioconductor. Then Go enrichment and KEGG pathway analysis were performed on the selected differential genes by use of the DAVID online tool. A regulation network of miRNA gene was constructed and analyzed by Cytoscape. Finally, we performed ROC analysis of 8 miRNAs and ROC curves were drawn. RESULTS A total of 159 DEMs and 1921 DEGs were screened, and 1881 pairs of miRNA-target genes with significant negative correlations were also obtained. A regulatory network of miRNA-gene, including 60 cancer-related genes and 47 miRNAs, was successfully constructed. In addition, 5 clusters with several miRNAs regulating a set of target genes simultaneously were identified through cluster analysis. There were 8 miRNAs involved in these 5 clusters, and these miRNAs could serve as molecular biomarkers to distinguish colon adenocarcinoma and normal samples indicated by ROC analysis. CONCLUSIONS The identified 8 miRNAs were closely associated with colon adenocarcinoma, which may have great clinical value as diagnostic and prognostic biomarkers and provide new ideas for targeted therapy. PMID- 26868023 TI - Perchlorate as an emerging contaminant in soil, water and food. AB - Perchlorate ( [Formula: see text] ) is a strong oxidizer and has gained significant attention due to its reactivity, occurrence, and persistence in surface water, groundwater, soil and food. Stable isotope techniques (i.e., ((18)O/(16)O and (17)O/(16)O) and (37)Cl/(35)Cl) facilitate the differentiation of naturally occurring perchlorate from anthropogenic perchlorate. At high enough concentrations, perchlorate can inhibit proper function of the thyroid gland. Dietary reference dose (RfD) for perchlorate exposure from both food and water is set at 0.7 MUg kg(-1) body weight/day which translates to a drinking water level of 24.5 MUg L(-1). Chromatographic techniques (i.e., ion chromatography and liquid chromatography mass spectrometry) can be successfully used to detect trace level of perchlorate in environmental samples. Perchlorate can be effectively removed by wide variety of remediation techniques such as bio-reduction, chemical reduction, adsorption, membrane filtration, ion exchange and electro-reduction. Bio-reduction is appropriate for large scale treatment plants whereas ion exchange is suitable for removing trace level of perchlorate in aqueous medium. The environmental occurrence of perchlorate, toxicity, analytical techniques, removal technologies are presented. PMID- 26868025 TI - Tracking the release of IPCC AR5 on Twitter: Users, comments, and sources following the release of the Working Group I Summary for Policymakers. AB - Using the immediate release of the Working Group 1 Summary for Policymakers of the Intergovernmental Panel on Climate Change Fifth Assessment Report as a case study, this article seeks to describe what type of actors were most active during the summary release, the substance of the most propagated tweets during the summary release, and the media sources that attracted the most attention during the summary release. The results from the study suggest that non-elite actors, such as individual bloggers and concerned citizens, accounted for the majority of the most propagated tweets in the sample. This study also finds that the majority of the most propagated tweets in the sample focused on public understanding of the report. Finally, while mainstream media sources were the most frequently discussed media sources, a number of new media and science news and information sources compete for audience attention. PMID- 26868024 TI - Chicken sperm transcriptome profiling by microarray analysis. AB - It has been confirmed that mammalian sperm contain thousands of functional RNAs, and some of them have vital roles in fertilization and early embryonic development. Therefore, we attempted to characterize transcriptome of the sperm of fertile chickens using microarray analysis. Spermatozoal RNA was pooled from 10 fertile males and used for RNA preparation. Prior to performing the microarray, RNA quality was assessed using a bioanalyzer, and gDNA and somatic cell RNA contamination was assessed by CD4 and PTPRC gene amplification. The chicken sperm transcriptome was cross-examined by analysing sperm and testes RNA on a 4 * 44K chicken array, and results were verified by RT-PCR. Microarray analysis identified 21,639 predominantly nuclear-encoded transcripts in chicken sperm. The majority (66.55%) of the sperm transcripts were shared with the testes, while surprisingly, 33.45% transcripts were detected (raw signal intensity greater than 50) only in the sperm and not in the testes. The greatest proportion of up-regulated transcripts were responsible for signal transduction (63.20%) followed by embryonic development (56.76%) and cell structure (56.25%). Of the 20 most abundant transcripts, 18 remain uncharacterized, whereas the least abundant genes were mostly associated with the ribosome. These findings lay a foundation for more detailed investigations on sperm RNAs in chickens to identify sperm-based biomarkers for fertility. PMID- 26868026 TI - Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of at least two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20% of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed. PMID- 26868027 TI - Status quo and directions in deep head and neck hyperthermia. AB - The benefit of hyperthermia as a potent modifier of radiotherapy has been well established and more recently also the combination with chemotherapy was shown beneficial. Also for head and neck cancer, the impact of hyperthermia has been clinically demonstrated by a number of clinical trials. Unfortunately, the technology applied in these studies provided only limited thermal dose control, and the devices used only allowed treatment of target regions close to the skin. Over the last decade, we developed the technology for deep and controlled hyperthermia that allows treatment of the entire head and neck region. Our strategy involves focused microwave heating combined with 3D patient-specific electromagnetic and thermal simulations for conformal, reproducible and adaptive hyperthermia application. Validation of our strategy has been performed by 3D thermal dose assessment based on invasively placed temperature sensors combined with the 3D patient specific simulations. In this paper, we review the phase III clinical evidence for hyperthermia in head and neck tumors, as well as the heating and dosimetry technology applied in these studies. Next, we describe the development, clinical implementation and validation of 3D guided deep hyperthermia with the HYPERcollar, and its second generation, i.e. the HYPERcollar3D. Lastly, we discuss early clinical results and provide an outlook for this technology. PMID- 26868028 TI - The fate of fertilizer nitrogen in a high nitrate accumulated agricultural soil. AB - Well-acclimatized nitrifiers in high-nitrate agricultural soils can quickly nitrify NH4(+) into NO3(-) subject to leaching and denitrifying loss. A 120-day incubation experiment was conducted using a greenhouse soil to explore the fates of applied fertilizer N entering into seven soil N pools and to examine if green manure (as ryegrass) co-application can increase immobilization of the applied N into relatively stable N pools and thereby reduce NO3(-) accumulation and loss. We found that 87-92% of the applied (15)N-labelled NH4(+) was rapidly recovered as NO3(-) since day 3 and only 2-4% as microbial biomass and soil organic matter (SOM), while ryegrass co-application significantly decreased its recovery as NO3( ) but enhanced its recovery as SOM (17%) at the end of incubation. The trade-off relationship between (15)N recoveries in microbial biomass and SOM indicated that ryegrass co-application stabilized newly immobilized N via initial microbial uptake and later breakdown. Nevertheless, ryegrass application didn't decrease soil total NO3(-) accumulation due to its own decay. Our results suggest that green manure co-application can increase immobilization of applied N into stable organic N via microbial turnover, but the quantity and quality of green manure should be well considered to reduce N release from itself. PMID- 26868029 TI - Improved lenticule shape for hyperopic femtosecond lenticule extraction (ReLEx FLEx): a pilot study. AB - The aim of this study is to establish and to prove a new lenticule shape for the treatment of hyperopia using a 500 kHz femtosecond laser and the femtosecond lenticule extraction (ReLEx FLEx) technique. Improved lenticule shapes with a large transition zone of at least 2 mm adjusted to the 5.75 mm optical zone were designed. A prospective pilot study on nine eyes of five patients who underwent an uncomplicated FLEx using VisuMax femtosecond laser (Carl Zeiss Meditec AG) for spherical hyperopia was performed. Patients' mean age was 55.5 years, and the preoperative manifest spherical equivalent (SE) was +1.82 D (range +1.25 to +3.00 D). Because of the presbyopic age and in order to compensate for a possible regression, the treatment was aimed at low myopia (mean target SE was -0.88 D with a mean treatment refraction of +2.69 D). At the last follow-up, after 9 months, 33% were within +/-0.50 D and 78% within +/-1.00 D of intended correction. Thirty-three percent lost one line, and 11% gained one line corrected distance visual acuity (CDVA). On average, the centre of the optical zone was 0.34 +/- 0.17 mm from the corneal vertex. No adverse effects were observed. This pilot study confirms that the improved lenticule's design with a large optical and transition zone can achieve good centration and acceptable results for spherical hyperopia using FLEx. The next steps are to extend the study to spherocylindrical hyperopic treatments and to increase the number of eyes for better assessment of refractive outcome. PMID- 26868030 TI - Carbon dioxide laser ablation of dermatosis papulosa nigra: high satisfaction and few complications in patients with pigmented skin. AB - Dermatosis papulosa nigra (DPN) is a common condition of pigmented skin. Whilst lesions are benign, they may be symptomatic or cosmetically disfiguring. Ablative lasers have previously been reported as a useful therapeutic modality in DPN. We report the largest case series to date of patients with DPN ablated with the carbon dioxide (CO2) laser. A retrospective case note review was conducted of all patients with DPN treated in our laser clinic in the last five years, and a post treatment telephone survey was undertaken to assess patient satisfaction. Forty five patients were identified, with a median age of 41 years (range 25-74 years), of whom 37 (82%) were female. The median number of treatments undertaken was three (range 1-10). Of the 18 respondents to the telephone survey, when asked to grade their satisfaction with the procedure out of 10, median response was 9.5 (range 6-10) with nine patients citing the maximum score of 10. All patients replied that their confidence had improved following the procedure and that they would recommend the treatment to other patients. Five respondents (28%) reported recurrence of a few lesions following CO2 laser ablation; the remaining 13 respondents (72%) reported no recurrence of DPN. No respondents reported any other post-procedural complications (including scarring, hypopigmentation and hyperpigmentation). We advocate use of the CO2 laser as a safe, convenient means of treating DPN, with a high degree of patient satisfaction, low recurrence rate and few complications. PMID- 26868031 TI - Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats. AB - The aim of the present study was to evaluate the effects of photobiomodulation (PBM) on cytokine levels and angiogenesis during oral wound healing. Ulcers were made on the dorsum of the tongue in 48 Wistar rats. Irradiation with an indium gallium-aluminum-phosphide (InGaAlP) laser (660 nm; output power, 40 mW; spot size, 0.04 cm(2)) was performed once a day on two points of the ulcer for 14 days. Two different energy densities were used: 4 J/cm(2) (energy per point 0.16 J, total energy 0.32 J) and 20 J/cm(2) (energy per point 0.8 J, total energy 1.6 J). Tissue levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha were investigated by enzyme-linked immunosorbent assay (ELISA). Image analysis of CD31-immunostained sections was used to investigate microvessel density (MVD). PBM increased the tissue levels of IL-1beta at the early stage of oral wound healing (p < 0.01) and increased the tissue levels of TNF-alpha during all stages of oral wound healing (p < 0.05). PBM at a dose of 4 J/cm(2) produced more significant results regarding cytokine modulation and was associated with higher MVD at day 5. Collectively, these findings indicate that cytokine modulation and increased angiogenesis are among the basic mechanisms whereby PBM improves oral wound repair. PMID- 26868032 TI - Greenlight high-performance system (HPS) 120-W laser vaporization versus transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: a meta-analysis of the published results of randomized controlled trials. AB - To assess the efficacy and the safety of Greenlight(TM) high-performance system (HPS) 120-W laser photoselective vaporization of the prostate (PVP) compared with transurethral resection of the prostate (TURP) for treatment of benign prostatic hyperplasia (BPH). The related original studies only including randomized controlled trials were searched by databases MEDLINE, EMBASE, Google Scholar, and the Cochrane Controlled Trial Register. The databases were updated till July 2014. The risk ratio, mean difference, and their corresponding 95% confidence intervals were calculated. Risk of bias of the enrolled trials were assessed according to Cochrane Handbook. A total of four trials involving 559 patients were enrolled. Statistical analysis was performed by software Review Manager (V5.3.3). There was no significant difference in International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) between PVP and TURP at 6-, 12-, and 24 month follow-up. Patients in the PVP group were associated with significantly lower risk of capsule perforation (risk ratio (RR) = 0.06, 95% confidence interval (95%CI) = 0.01 to 0.46; p = 0.007), significantly lower transfusion requirements (RR = 0.12, 95%CI = 0.03 to 0.43; p = 0.001), a shorter catheterization time (mean difference (MD) = -41.93, 95%CI = -54.87 to -28.99; p < 0.00001), and a shorter duration of hospital stay (MD = -2.09, 95%CI = -2.58 to -1.59; p < 0.00001) than that in the TURP group. In the TURP group, the patients were associated with a lower risk of re-operation (RR = 3.68, 95%CI = 1.04 to 13.00; p = 0.04) and a shorter operative time (MD = 9.28, 95%CI = 2.80 to 15.75; p = 0.005) than those in the PVP group. In addition, no statistically significant differences were detected between groups in terms of the rates of transurethral resection syndrome, urethral stricture, bladder neck contracture, incontinence, and infection. Greenlight(TM) 120-W laser PVP is as effective as TURP for symptom reduction and improvement of the quality of life. Laser PVP shows advantages over TURP in terms of intraoperative safety, whereas TURP is found to have a shorter operative time and lower re-operative risk. PMID- 26868033 TI - Effects of low level laser therapy on the prognosis of split-thickness skin graft in type 3 burn of diabetic patients: a case series. AB - Significant populations in burn centers are diabetic burn patients. Healing process in these patients is more difficult due to diabetes complications. The gold standard treatment for patients with grade 3 burn ulcer is split-thickness skin grafting (STSG), but in the diabetic patients, the rate of graft failure and amputation is high due to impaired tissue perfusion. The technique of low level laser therapy (LLLT) improves tissue perfusion and fibroblast proliferation, increases collagen synthesis, and accelerates wound healing. The purpose of this case report is introducing a new therapeutic method for accelerating healing with better prognosis in these patients. The protocols and informed consent were reviewed according to the Medical Ethics, Board of Shahid Beheshti Medical Sciences (IR.SBMU.RAM.REC.13940.363). Diabetic type 2 patients with 13 grade 3 burn ulcers, candidate for amputation, were enrolled in the study. We used a 650 nm red laser light, 2 J/Cm for the bed of the ulcer and an 810-nm infrared laser light 6 J/Cm(2) for the margins along with intravenous laser therapy with a 660 nm red light, before and after STSG for treating grade 3 burn ulcers in 13 diabetic ulcers. The results of this study showed complete healing in the last 8 weeks for all patients who were candidates for amputation. In this case series, we present 13 cases of diabetic ulcer with type 3 burn wound, candidate for amputation, who healed completely using LLLT and STSG. This is the first time that these two techniques are combined for treatment of burn ulcer in diabetic patients. Using LLLT with STSG might be a promising treatment for burn victims especially diabetic patients. PMID- 26868034 TI - Changes in Consumer Demand Following Public Reporting of Summary Quality Ratings: An Evaluation in Nursing Homes. AB - OBJECTIVE: Limited consumer use of health care report cards may be due to the large amount of information presented in report cards, which can be difficult to understand. These limitations may be overcome with summary measures. Our objective was to evaluate consumer response to summary measures in the setting of nursing homes. DATA SOURCES/STUDY SETTING: 2005-2010 nursing home Minimum Data Set and Online Survey, Certification and Reporting (OSCAR) datasets. STUDY DESIGN: In December 2008, Medicare converted its nursing home report card to summary or star ratings. We test whether there was a change in consumer demand for nursing homes related to the nursing home's star rating after the information was released. PRINCIPAL FINDINGS: The star rating system was associated with a significant change in consumer demand for low- and high-scoring facilities. After the star-based rating system was released, 1-star facilities typically lost 8 percent of their market share and 5-star facilities gained over 6 percent of their market share. CONCLUSIONS: The nursing home star rating system significantly affected consumer demand for high- and low-rated nursing homes. These results support the use of summary measures in report cards. PMID- 26868036 TI - Erratum to: Dynamics of Simple Food Webs. PMID- 26868035 TI - Preparation of Au-polydopamine functionalized carbon encapsulated Fe3O4 magnetic nanocomposites and their application for ultrasensitive detection of carcino embryonic antigen. AB - A novel carbon encapsulated Fe3O4 nanoparticles embedded in two-dimensional (2D) porous graphitic carbon nanocomposites (Fe3O4@C@PGC nanocomposites) were synthesized by situ synthesis strategy, which provided a sensor platform owing to a large aspect ratio and porous structure. Polydopamine (PDA) were modified on the surface of Fe3O4@C@PGC nanocomposites through self-polymerization of dopamine, acting as both the reductant and template for one-step synthesis of gold nanoparticles. The prepared Au/PDA/Fe3O4@C@PGC nanocomposites show ferromagnetic features, extremely excellent electron transfer, large specific surface area and excellent dispersing property. These are conducive to the electrochemical signal output and the immobilization of antibody. In this work, a highly label-free sensitive magnetic immunosensor was developed based on Au/PDA/Fe3O4@C@PGC nanocomposites for the detection of carcino-embryonic antigen (CEA). The magnetic glassy carbon electrode was used to fix the Au/PDA/Fe3O4@C@PGC nanocomposites with the help of magnetic force. Under the optimal conditions, the immunosensor exhibited a wide linear range (0.001 ng/mL 20.0 ng/mL), a low detection limit (0.33 pg/mL), good reproducibility, selectivity and acceptable stability. The proposed sensing strategy may provide a potential application in the detection of other cancer biomarkers. PMID- 26868037 TI - dTRPA1 in Non-circadian Neurons Modulates Temperature-dependent Rhythmic Activity in Drosophila melanogaster. AB - In fruit flies Drosophila melanogaster, environmental cycles of light and temperature are known to influence behavioral rhythms through dedicated sensory receptors. But the thermosensory pathways and molecular receptors by which thermal cycles modulate locomotor activity rhythms remain unclear. Here, we report that neurons expressing warmth-activated ion channel Drosophila Transient Receptor Potential-A1 (dTRPA1) modulate distinct aspects of the rhythmic activity/rest rhythm in a light-dependent manner. Under light/dark (LD) cycles paired with constantly warm ambient conditions, flies deficient in dTRPA1 expression are unable to phase morning and evening activity bouts appropriately. Correspondingly, we show that electrical activity of a few neurons targeted by the dTRPA1(SH)-GAL4 driver modulates temperature-dependent phasing of activity/rest rhythm under LD cycles. The expression of dTRPA1 also affects behavior responses to temperature cycles combined with constant dark (DD) or light (LL) conditions. We demonstrate that the mid-day "siesta" exhibited by flies under temperature cycles in DD is dependent on dTRPA1 expression in a small number of neurons that include thermosensory anterior cell neurons. Although a small subset of circadian pacemaker neurons may express dTRPA1, we show that CRY negative dTRPA1(SH)-GAL4 driven neurons are critical for the suppression of mid thermophase activity, thus enabling flies to exhibit siesta. In contrast to temperature cycles in DD, under LL, dTRPA1 is not required for exhibiting siesta but is important for phasing of evening peak. Our studies show that activity/rest rhythms are modulated in a temperature-dependent manner via signals from dTRPA1(SH)-GAL4 driven neurons. Taken together, these results emphasize the differential influence of thermoreceptors on rhythmic behavior in fruit flies in coordination with light inputs. PMID- 26868038 TI - Porcelain lung: calcification in severe Bordetella pertussis infection. PMID- 26868039 TI - Managing the child with a diagnosis of Moebius syndrome: more than meets the eye. AB - Moebius syndrome (MBS) is a congenital, non-progressive facial and abducens nerve palsy in the presence of full vertical gaze and may be associated with limb abnormalities and craniofacial dysmorphisms. MBS is now defined as a disorder of rhombencephalic maldevelopment and recent gene discoveries have shown this to be a dominant disorder in a subset of patients. Accurate diagnosis and management by a multidisciplinary team with expertise in congenital facial palsy is paramount. PMID- 26868040 TI - Deformation-induced trace element redistribution in zircon revealed using atom probe tomography. AB - Trace elements diffuse negligible distances through the pristine crystal lattice in minerals: this is a fundamental assumption when using them to decipher geological processes. For example, the reliable use of the mineral zircon (ZrSiO4) as a U-Th-Pb geochronometer and trace element monitor requires minimal radiogenic isotope and trace element mobility. Here, using atom probe tomography, we document the effects of crystal-plastic deformation on atomic-scale elemental distributions in zircon revealing sub-micrometre-scale mechanisms of trace element mobility. Dislocations that move through the lattice accumulate U and other trace elements. Pipe diffusion along dislocation arrays connected to a chemical or structural sink results in continuous removal of selected elements (for example, Pb), even after deformation has ceased. However, in disconnected dislocations, trace elements remain locked. Our findings have important implications for the use of zircon as a geochronometer, and highlight the importance of deformation on trace element redistribution in minerals and engineering materials. PMID- 26868042 TI - Expanding perspectives on cognition in humans, animals, and machines. AB - Over the past decade neuroscience has been attacking the problem of cognition with increasing vigor. Yet, what exactly is cognition, beyond a general signifier of anything seemingly complex the brain does? Here, we briefly review attempts to define, describe, explain, build, enhance and experience cognition. We highlight perspectives including psychology, molecular biology, computation, dynamical systems, machine learning, behavior and phenomenology. This survey of the landscape reveals not a clear target for explanation but a pluralistic and evolving scene with diverse opportunities for grounding future research. We argue that rather than getting to the bottom of it, over the next century, by deconstructing and redefining cognition, neuroscience will and should expand rather than merely reduce our concept of the mind. PMID- 26868041 TI - Canonical computations of cerebral cortex. AB - The idea that there is a fundamental cortical circuit that performs canonical computations remains compelling though far from proven. Here we review evidence for two canonical operations within sensory cortical areas: a feedforward computation of selectivity; and a recurrent computation of gain in which, given sufficiently strong external input, perhaps from multiple sources, intracortical input largely, but not completely, cancels this external input. This operation leads to many characteristic cortical nonlinearities in integrating multiple stimuli. The cortical computation must combine such local processing with hierarchical processing across areas. We point to important changes in moving from sensory cortex to motor and frontal cortex and the possibility of substantial differences between cortex in rodents vs. species with columnar organization of selectivity. PMID- 26868043 TI - Brain structure and dynamics across scales: in search of rules. AB - Louis Henry Sullivan, the father of skyscrapers, famously stated 'Form ever follows function'. In this short review, we will focus on the relationship between form (structure) and function (dynamics) in the brain. We summarize recent advances on the quantification of directed- and weighted-mesoscopic connectivity of mammalian cortex, the exponential distance rule for mesoscopic and microscopic circuit wiring, a spatially embedded random model of inter-areal cortical networks, and a large-scale dynamical circuit model of money's cortex that gives rise to a hierarchy of timescales. These findings demonstrate that inter-areal cortical networks are dense (hence such concepts as 'small-world' need to be refined when applied to the brain), spatially dependent (therefore purely topological approach of graph theory has limited applicability) and heterogeneous (consequently cortical areas cannot be treated as identical 'nodes'). PMID- 26868044 TI - Strategies for parenting by mothers and fathers with a mental illness. AB - WHAT IS KNOWN ON THE SUBJECT?: The combination of coping with their mental health problems and caring for children makes parents vulnerable. Family-centred practice can help to maintain and strengthen important family relationships, and to identify and enhance the strengths of a parent with a mental illness, all contributing to the recovery of the person with the mental illness. WHAT THIS PAPER ADDS TO THE EXISTING KNOWLEDGE?: Taking the strength and the opportunities formulated by parents themselves as a starting point is fairly new. Parents with severe mental illness find strength for parenting in several ways. They feel responsible, and this helps them to stay alert while parenting, whereas parenthood also offers a basis for social participation through school contacts and the child's friendships. Dedication to the parent role provides a focus; parents develop strengths and skills as they find a balance between attending to their own lives and caring for their children; and parenting prompts them to find adequate sources of social support. In this study these strategies were found to be the fundamentals of recovery related to parenting. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses can support and coach patients who are identified as parents, and self-chosen parenting related goals are set and addressed. A family focused approach by nurses can be used to prevent problems for children and their families, identify their strengths as well as vulnerabilities, and address the challenges to build resilience. INTRODUCTION: Understanding of the problems of parents with mental illness is growing. Gaining insight into strategies for parenting, while taking the opportunities formulated by these parents themselves as a starting point is fairly new. QUESTION: What are the strategies of parents with a mental illness to be successful? METHOD: Experiences of 19 mothers and eight fathers with a mental illness were explored with in-depth interviews. Data were content analysed, using qualitative methods. RESULTS: Next to feelings of inadequacy, interviewees also describe how children enrich and structure their lives and are not only a burden but serve as distraction from problems. Developing activities that interest both child and parent provides avenues for emerging strength. Mental illness constrains fathers, but also gives opportunities to develop a meaningful relation with their children. DISCUSSION: Strategies like being fully dedicated to the parental role, finding a balance between attention for one's own life and parenting and finding adequate sources of support are found to be fundamental for recovery in the parent role. Implications for practice Peer groups can be of valuable help and mental health workers can support parents to set self-chosen parenting related goals. PMID- 26868045 TI - The Milky Way educational and support programme: Structure, content and strategies. AB - BACKGROUND: Health professionals have put much effort into supporting women to continue breastfeeding up to six months and beyond. The majority of those efforts have not been successful for primiparous women. Primiparous women who engaged in the Milky Way Programme had an improvement in breastfeeding rates of almost 50% at six months when compared to women in a control group. PURPOSE: To provide details of the Milky Way Programme including the educational structure, content and strategies as well as the process of postnatal telephone support. OVERVIEW: The details of the Milky Way Programme are presented including a summary of literature review that was used to design the programme. The structure and content of the programme is then presented. Finally, the strategies with some practical examples are outlined in more detail. CONCLUSION: The programme is evidence-based, theoretically informed and woman-centred. This paper provides the necessary information to health professionals who are trained to educate and support breastfeeding women to implement similar programmes in their workplaces. PMID- 26868046 TI - A novel algorithm for detecting active propulsion in wheelchair users following spinal cord injury. AB - Physical activity in wheelchair-bound individuals can be assessed by monitoring their mobility as this is one of the most intense upper extremity activities they perform. Current accelerometer-based approaches for describing wheelchair mobility do not distinguish between self- and attendant-propulsion and hence may overestimate total physical activity. The aim of this study was to develop and validate an inertial measurement unit based algorithm to monitor wheel kinematics and the type of wheelchair propulsion (self- or attendant-) within a "real-world" situation. Different sensor set-ups were investigated, ranging from a high precision set-up including four sensor modules with a relatively short measurement duration of 24 h, to a less precise set-up with only one module attached at the wheel exceeding one week of measurement because the gyroscope of the sensor was turned off. The "high-precision" algorithm distinguished self- and attendant-propulsion with accuracy greater than 93% whilst the long-term measurement set-up showed an accuracy of 82%. The estimation accuracy of kinematic parameters was greater than 97% for both set-ups. The possibility of having different sensor set-ups allows the use of the inertial measurement units as high precision tools for researchers as well as unobtrusive and simple tools for manual wheelchair users. PMID- 26868047 TI - Expression levels of ABCG2 on cord red blood cells and study of fetal anemia associated with anti-Jr(a). AB - BACKGROUND: The Jr(a) antigen of JR blood group systems is located on ABCG2 and Jr(a-) subjects whose red blood cells (RBCs) lack ABCG2 have been identified mostly among the Japanese. Although anti-Jr(a) can cause fetal anemia, little is known regarding its mechanism. STUDY DESIGN AND METHODS: We reviewed clinical courses of all reported cases with fetal anemia due to anti-Jr(a) . We analyzed the ABCG2 expressions of cord RBCs at various gestational ages. We examined the effects of sera containing anti-Jr(a) from three pregnancies with fetal anemia or monoclonal anti-Jr(a) on erythropoiesis and phagocytosis. We also examined epitopes of anti-Jr(a) . RESULTS: Case series suggested that the majority of fetal anemia with anti-Jr(a) may not be progressive in the later gestational ages. ABCG2 expression levels of cord RBCs were significantly higher than those of adults and neonates with high individual variation and gradually decreased with advancing gestational ages. Anti-Jr(a) did not significantly impact erythroid colony formation, although we detected a tendency toward the suppression of erythroid burst-forming unit formation by anti-Jr(a) using feline marrow cells. Anti-Jr(a) did not induce phagocytosis of sensitized RBCs by monocytes. While many anti-Jr(a) recognized the same regions as a monoclonal anti ABCG2, 5D3, epitopes of anti-Jr(a) did not correlate with the incidence of fetal anemia. CONCLUSION: ABCG2 expression levels in cord RBCs are higher than those of adults, and the change of ABCG2 expression in erythroid lineage cells may influence the clinical course of fetal anemia with anti-Jr(a) , although we could not detect significant effects of anti-Jr(a) on erythroid colony formation or phagocytosis. PMID- 26868049 TI - Periodic Mesoporous Organosilica Nanocubes with Ultrahigh Surface Areas for Efficient CO2 Adsorption. AB - Ultrahigh surface area single-crystals of periodic mesoporous organosilica (PMOs) with uniform cubic or truncated-cubic morphology and organic/inorganic components homogeneously distributed over the whole frameworks have successfully been prepared by a sol-gel surfactant-templating method. By tuning the porous feature and polymerization degree, the surface areas of the obtained PMO nanocubes can reach as high as 2370 m(2)/g, which is the highest for silica-based mesoporous materials. The ultrahigh surface area of the obtained PMO single crystals is mainly resulted from abundant micropores in the mesoporous frameworks. Furthermore, the diameter of the nanocubes can also be well controlled from 150 to 600 nm. The materials show ultrahigh CO2 adsorption capacity (up to 1.42 mmol/g at 273 K) which is much higher than other porous silica materials and comparable to some carbonaceous materials. The adsorption of CO2 into the PMO nanocubes is mainly in physical interaction, therefore the adsorption-desorption process is highly reversible and the adsorption capacity is much dependent on the surface area of the materials. Moreover, the selectivity is also very high (~11 times to N2) towards CO2 adsorption. PMID- 26868048 TI - Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study. AB - The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 +/- 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases. PMID- 26868050 TI - Specialist availability in emergencies: contributions of response times and the use of ad hoc coverage in New York State. AB - OBJECTIVES: Nationwide, hospitals struggle to maintain specialist on-call coverage for emergencies. We seek to further understand the issue by examining reliability of scheduled coverage and the role of ad hoc coverage when none is scheduled. METHODS: An anonymous electronic survey of all emergency department (ED) directors of a large state. Overall and for 10 specialties, respondents were asked to estimate on-call coverage extent and "reliability" (frequency of emergency response in a clinically useful time frame: 2 hours), and use and effect of ad hoc emergency coverage to fill gaps. Descriptive statistics were performed using Fisher exact and Wilcoxon sign rank tests for significance. RESULTS: Contact information was obtained for 125 of 167 ED directors. Sixty responded (48%), representing 36% of EDs. Forty-six percent reported full on-call coverage scheduled for all specialties. Forty-six percent reported consistent reliability. Coverage and reliability were strongly related (P<.01; 33% reported both), and larger ED volume correlated with both (P<.01). Ninety percent of hospitals that had gaps in either employed ad hoc coverage, significantly improving coverage for 8 of 10 specialties. For all but 1 specialty, more than 20% of hospitals reported that specialists are "Never", "Rarely" or "Sometimes" reliable (more than 50% for cardiovascular surgery, hand surgery and ophthalmology). CONCLUSIONS: Significant holes in scheduled on-call specialist coverage are compounded by frequent unreliability of on-call specialists, but partially ameliorated by ad hoc specialist coverage. Regionalization may help because a 2-tiered system may exist: larger hospitals have more complete, reliable coverage. Better understanding of specialists' willingness to treat emergencies ad hoc without taking formal call will suggest additional remedies. PMID- 26868051 TI - Investigation of cell death mechanisms in human lymphatic endothelial cells undergoing photodynamic therapy. AB - BACKGROUND: Photodynamic therapy (PDT) has been shown to induce ablation and functional occlusion of tumor-associated lymphatic vessels. However, direct effects of PDT on lymphatic endothelial cells (LECs) have not been studied so far. The aim of this study was to elucidate molecular mechanisms of cell death induced by PDT in human LECs. METHODS: Verteporfin was used as a photosensitizer to investigate PDT-mediated damage of lymphatic vessels in mice using immunofluorescent staining and stereomicroscopy. In vitro dose-response studies were carried-out with crystal violet staining. Immunofluorescence, flow cytometry, immunoblotting and DNA electrophoresis were used to investigate the mechanisms of cell death in human LECs undergoing PDT. RESULTS: PDT induced an increase in the number of propidium iodide positive lymphatic endothelial cells in the mouse dermis. In in vitro studies dose-dependent cytotoxic effects of PDT towards LECs were observed. Typical hallmarks of apoptotic cell death, including Annexin V binding, loss of mitochondrial membrane potential, caspase activation, cleavage of PARP as well as DNA fragmentation were observed in LECs when PDT was used at high irradiation conditions, causing >80% cell death. At lower light fluencies causing <50% cell death PDT induced autophagy rather than apoptosis, as revealed by conversion of LC3-I to the autophagosomal LC3-II and formation of LC3 puncta. Z-VAD-FMK, a caspase inhibitor, prevented cell death induced by high-dose PDT only, while 3-methyladenine, an autophagy suppressor, inhibited cell death induced by low-dose PDT. CONCLUSIONS: Both apoptosis and autophagy are involved in cell death induced by verteporfin-PDT in LECs. PMID- 26868052 TI - Portal of medical data models: information infrastructure for medical research and healthcare. AB - INTRODUCTION: Information systems are a key success factor for medical research and healthcare. Currently, most of these systems apply heterogeneous and proprietary data models, which impede data exchange and integrated data analysis for scientific purposes. Due to the complexity of medical terminology, the overall number of medical data models is very high. At present, the vast majority of these models are not available to the scientific community. The objective of the Portal of Medical Data Models (MDM, https://medical-data-models.org) is to foster sharing of medical data models. METHODS: MDM is a registered European information infrastructure. It provides a multilingual platform for exchange and discussion of data models in medicine, both for medical research and healthcare. The system is developed in collaboration with the University Library of Munster to ensure sustainability. A web front-end enables users to search, view, download and discuss data models. Eleven different export formats are available (ODM, PDF, CDA, CSV, MACRO-XML, REDCap, SQL, SPSS, ADL, R, XLSX). MDM contents were analysed with descriptive statistics. RESULTS: MDM contains 4387 current versions of data models (in total 10,963 versions). 2475 of these models belong to oncology trials. The most common keyword (n = 3826) is 'Clinical Trial'; most frequent diseases are breast cancer, leukemia, lung and colorectal neoplasms. Most common languages of data elements are English (n = 328,557) and German (n = 68,738). Semantic annotations (UMLS codes) are available for 108,412 data items, 2453 item groups and 35,361 code list items. Overall 335,087 UMLS codes are assigned with 21,847 unique codes. Few UMLS codes are used several thousand times, but there is a long tail of rarely used codes in the frequency distribution. DISCUSSION: Expected benefits of the MDM portal are improved and accelerated design of medical data models by sharing best practice, more standardised data models with semantic annotation and better information exchange between information systems, in particular Electronic Data Capture (EDC) and Electronic Health Records (EHR) systems. Contents of the MDM portal need to be further expanded to reach broad coverage of all relevant medical domains. Database URL: https://medical-data models.org. PMID- 26868053 TI - The Corvids Literature Database--500 years of ornithological research from a crow's perspective. AB - Corvids (Corvidae) play a major role in ornithological research. Because of their worldwide distribution, diversity and adaptiveness, they have been studied extensively. The aim of the Corvids Literature Database (CLD, http://www.corvids.de/cld) is to record all publications (citation format) on all extant and extinct Crows, Ravens, Jays and Magpies worldwide and tag them with specific keywords making them available for researchers worldwide. The self maintained project started in 2006 and today comprises 8000 articles, spanning almost 500 years. The CLD covers publications from 164 countries, written in 36 languages and published by 8026 authors in 1503 journals (plus books, theses and other publications). Forty-nine percent of all records are available online as full-text documents or deposited in the physical CLD archive. The CLD contains 442 original corvid descriptions. Here, we present a metadata assessment of articles recorded in the CLD including a gap analysis and prospects for future research. Database URL: http://www.corvids.de/cld. PMID- 26868054 TI - CCSI: a database providing chromatin-chromatin spatial interaction information. AB - Distal regulatory elements have been shown to regulate gene transcription through spatial interactions, and single nucleotide polymorphisms (SNPs) are linked with distal gene expression by spatial proximity, which helps to explain the causal role of disease-associated SNPs in non-coding region. Therefore, studies on spatial interactions between chromatin have created a new avenue for elucidating the mechanism of transcriptional regulation in disease pathogenesis. Recently, a growing number of chromatin interactions have been revealed by means of 3C, 4C, 5C, ChIA-PET and Hi-C technologies. To interpret and utilize these interactions, we constructed chromatin-chromatin spatial interaction (CCSI) database by integrating and annotating 91 sets of chromatin interaction data derived from published literature, UCSC database and NCBI GEO database, resulting in a total of 3,017,962 pairwise interactions (false discovery rate < 0.05), covering human, mouse and yeast. A web interface has been designed to provide access to the chromatin interactions. The main features of CCSI are (i) showing chromatin interactions and corresponding genes, enhancers and SNPs within the regions in the search page; (ii) offering complete interaction datasets, enhancer and SNP information in the download page; and (iii) providing analysis pipeline for the annotation of interaction data. In conclusion, CCSI will facilitate exploring transcriptional regulatory mechanism in disease pathogenesis associated with spatial interactions among genes, regulatory regions and SNPs. Database URL: http://songyanglab.sysu.edu.cn/ccsi. PMID- 26868055 TI - A meta-analysis of leaf gas exchange and water status responses to drought. AB - Drought is considered to be one of the most devastating natural hazards, and it is predicted to become increasingly frequent and severe in the future. Understanding the plant gas exchange and water status response to drought is very important with regard to future climate change. We conducted a meta-analysis based on studies of plants worldwide and aimed to determine the changes in gas exchange and water status under different drought intensities (mild, moderate and severe), different photosynthetic pathways (C3 and C4) and growth forms (herbs, shrubs, trees and lianas). Our results were as follows: 1) drought negatively impacted gas exchange and water status, and stomatal conductance (gs) decreased more than other physiological traits and declined to the greatest extent in shrubs and C3 plants. Furthermore, C4 plants had an advantage compared to C3 plants under the same drought conditions. 2) The decrease in gs mainly reduced the transpiration rate (Tr), and gs could explain 55% of the decrease in the photosynthesis (A) and 74% of the decline in Tr. 3). Finally, gas exchange showed a close relationship with the leaf water status. Our study provides comprehensive information about the changes in plant gas exchange and water status under drought. PMID- 26868056 TI - Proprotein convertase 7 rs236918 associated with liver fibrosis in Italian patients with HFE-related hemochromatosis. AB - BACKGROUND AND AIM: p.Cys282Tyr homozygosity is the prevalent genotype in (HFE) related Hereditary Hemochromatosis with low penetrance and variable expression. However, liver cirrhosis and hepatocellular carcinoma remain the main causes of mortality in these patients. Detection of genetic modifiers identifying patients at risk for liver damage would be relevant for their clinical management. We evaluated proprotein convertase 7 (PCSK7) rs236918 as genetic marker of risk of liver fibrosis in an Italian cohort of p.Cys282Tyr homozygotes. METHODS: Liver fibrosis was histologically assessed by Ishak score. We evaluated PCSK7 alleles and genotypes frequencies according to single or grouped staging scores: absent/mild fibrosis (stage: 0-2), moderate (stage: 3-4), and severe fibrosis/cirrhosis (stage: 5-6). Single nucleotide polymorphism genotyping was performed by restriction fragment length polymorphism or Taqman 5'-nuclease assays. RESULTS: The rs236918 allele C frequency increased from stages 0-2 to 5-6 (7.1% vs 13.6%, vs 21.9%, P = 0.003). The wild-type genotype was significantly more frequent in the absent/mild fibrosis group (54.2%) compared with only 17% in patients with severe fibrosis/cirrhosis. At univariate proportional odds model, patients with GC + CC genotypes were 2.77 times (P = 0.0018) more likely to have worse liver staging scores than wild-type patients. In the adjusted analysis, odds ratio was 2.37 (P = 0.0218), and 2.56 (P = 0.0233) when the analysis was restricted to males. An exploratory mediation analysis suggested a direct effect of genotype on severe fibrosis/cirrhosis (odds ratio = 3.11, P = 0.0157), and a mild non-significant indirect effect mediated through iron accounting for 28%. CONCLUSIONS: These findings confirm that PCSK7 rs236918 C allele is a risk factor for cirrhosis development in Italian patients with HFE-Hemochromatosis. PMID- 26868057 TI - The perspectives of stakeholders of intellectual disability liaison nurses: a model of compassionate, person-centred care. AB - AIMS AND OBJECTIVES: To investigate the experiences of patients with intellectual disabilities, family and paid carers regarding the role of liaison nurses and the delivery of compassionate, person-centred care. From this to propose a model of person-centred care embedded in these experiences. BACKGROUND: People with intellectual disabilities have a high number of comorbidities, requiring multidisciplinary care, and are at high risk of morbidity and preventable mortality. Provision of compassionate, person-centred care is essential to prevent complications and avoid death. DESIGN: A qualitative design was adopted with Interpretative Phenomenological Analysis for data analysis. METHODS: Semistructured interviews and focus groups were conducted. Data were analysed with a focus on compassionate, person-centred care elements and components. Themes were modelled to develop a clinically meaningful model for practice. RESULTS: Themes identified vulnerability, presence and the human interface; information balance; critical points and broken trust; roles and responsibilities; managing multiple transitions; 'flagging up' and communication. CONCLUSIONS: The findings provide the first 'anatomy' of compassionate, person centred care and provide a model for operationalising this approach in practice. The applicability of the model will have to be evaluated further with this and other vulnerable groups. RELEVANCE TO CLINICAL PRACTICE: This is the first study to provide a definition of compassionate, person-centred care and proposes a model to support its application into clinical practice for this and other vulnerable groups. PMID- 26868058 TI - Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia. AB - Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia. PMID- 26868059 TI - Agreement between health utility instruments in cochlear implantation. AB - OBJECTIVES: The objectives of our study were threefold: to compare health utility scores measured with different health utility instruments in adult patients with bilateral deafness, to compare the change in health utility scores after unilateral or bilateral cochlear implantation using the different health utility instruments and to assess which health utility instrument would be the most appropriate for future studies on cochlear implantation. DESIGN: A prospective study. SETTING: The data for this article were collected as part of a multicentre randomised controlled trial in the Netherlands on the benefits of simultaneous bilateral cochlear implantation compared to unilateral cochlear implantation. PARTICIPANTS: The study included 38 adult patients with severe to profound bilateral post-lingual sensorineural hearing loss. MAIN OUTCOME MEASURES: Participants completed various quality of life questionnaires (the EuroQol five dimensional questionnaire (EQ-5D), the Health Utilities Index mark 3 (HUI3), a visual analogue scale (VAS) for general quality of life and a VAS for hearing) preoperatively, and one and two years postoperatively. The general health utility instruments (EQ-5D, HUI3 and VAS general) were compared. RESULTS: The EQ-5D, HUI3 and VAS general utility scores differed significantly. The intraclass correlation coefficients showed poor to no agreement between these instruments. A gain in health utility after cochlear implantation was found with the HUI3 and VAS general. The highest gain in health utility was found with the HUI3. CONCLUSIONS: A health utility score depends on the health utility instrument that is used in a specific patient population. We recommend using the HUI3 in future studies on cochlear implantation. PMID- 26868060 TI - Report on milestones for care and support under the U.S. National Plan to Address Alzheimer's Disease. AB - INTRODUCTION: Under the U.S. national Alzheimer's plan, the National Institutes of Health identified milestones required to meet the plan's biomedical research goal (Goal 1). However, similar milestones have not been created for the goals on care (Goal 2) and support (Goal 3). METHODS: The Alzheimer's Association convened a workgroup with expertise in clinical care, long-term services and supports, dementia care and support research, and public policy. The workgroup reviewed the literature on Alzheimer's care and support; reviewed how other countries are addressing the issue; and identified public policies needed over the next 10 years to achieve a more ideal care and support system. RESULTS: The workgroup developed and recommended 73 milestones for Goal 2 and 56 milestones for Goal 3. DISCUSSION: To advance the implementation of the U.S. national Alzheimer's plan, the U.S. government should adopt these recommended milestones, or develop similar milestones, to be incorporated into the national plan. PMID- 26868061 TI - Multiple Imputation for General Missing Data Patterns in the Presence of High dimensional Data. AB - Multiple imputation (MI) has been widely used for handling missing data in biomedical research. In the presence of high-dimensional data, regularized regression has been used as a natural strategy for building imputation models, but limited research has been conducted for handling general missing data patterns where multiple variables have missing values. Using the idea of multiple imputation by chained equations (MICE), we investigate two approaches of using regularized regression to impute missing values of high-dimensional data that can handle general missing data patterns. We compare our MICE methods with several existing imputation methods in simulation studies. Our simulation results demonstrate the superiority of the proposed MICE approach based on an indirect use of regularized regression in terms of bias. We further illustrate the proposed methods using two data examples. PMID- 26868064 TI - A standardized formula based on 2D fetal thigh measurements improves the accuracy of intrapartum birth weight estimation. PMID- 26868062 TI - World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer. AB - BACKGROUND: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. METHODS: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. RESULTS: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. CONCLUSION: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries. PMID- 26868063 TI - Randomized controlled trial comparing ferric carboxymaltose and iron sucrose for treatment of iron deficiency anemia due to abnormal uterine bleeding. AB - OBJECTIVE: To evaluate the efficacy and safety of intravenous ferric carboxymaltose (FCM) in comparison with intravenous iron sucrose (ISC) in the treatment of anemia due to abnormal uterine bleeding (AUB). METHODS: A randomized controlled trial was conducted between April 2013 and May 2014 in patients older than 18 years of age presenting at a hospital in New Delhi, India, with anemia due to AUB. Patients were randomized in a 1:1 ratio to receive treatment with intravenous FCM or ISC. The primary outcome, increase in hemoglobin above baseline, was monitored over a 12-week period. Patients completing the full treatment and follow-up protocol were included in the analyses. Participants and investigators were not masked to treatment allocations. RESULTS: Overall, 30 patients were assigned to each group. Increases in mean hemoglobin levels from baseline were significantly higher in the FCM group at 6 weeks (P=0.005). At 12 weeks, there was no significant difference in hemoglobin increase from baseline between the two groups (P=0.11). Adverse events were similar between both treatment groups. CONCLUSION: Treatment with FCM resulted in a rapid increase in hemoglobin levels in patients with anemia due to AUB, with similar increases in hemoglobin over a 12-week period. Clinical Trial Registration (www.ctri.nic.in):CTRI/2015/09/006224. PMID- 26868065 TI - Economic implications of labor induction. AB - OBJECTIVE: To assess health service costs associated with labor induction according to different clinical situations in a tertiary-level hospital. METHODS: In a prospective study, individual patient cost data were assessed for women admitted for induction of labor at a tertiary hospital in Spain between November 1, 2012, and August 31, 2013. The costs of labor induction were estimated according to maternal and neonatal outcomes, method of delivery, cervical condition at admission, and obstetric indication. Direct costs including professional fees, epidural, maternal stay, consumables, and drugs were calculated. RESULTS: Overall, 412 women were included in the final cost analysis. The mean total cost of labor induction was ?3589.87 (95% confidence interval [CI] 3475.13-3704.61). Cesarean delivery after labor induction (?4830.45, 95% CI 4623.13-5037.58) was significantly more expensive than spontaneous delivery (?3037.45, 95% CI 2966.91-3179.99) and instrumental vaginal delivery (?3344.31, 95%CI 3151.69-3536.93). The total cost for patients with a very unfavorable cervix (Bishop score <2; ?4283.47, 95% CI 4063.06-4503.88) was almost double that for women with a favorable cervix (?2605.09, 95% CI 2327.38-2837.58). Labor induction for hypertensive disorders of pregnancy was the most expensive obstetric indication for induction of labor (?4347.32, 95% CI 3890.45-4804.18). CONCLUSION: Following the induction of labor, a number of patient- and treatment related factors influence costs associated with delivery. PMID- 26868067 TI - Importance of serial CA125 measurements over an absolute cut-off value for the detection of asymptomatic ovarian cancer in high-risk patients. PMID- 26868066 TI - Vitamin A status and its relationship with serum zinc concentrations among pregnant women who have previously undergone Roux-en-Y gastric bypass. AB - OBJECTIVE: To evaluate vitamin A status and its relationship with serum zinc concentrations among pregnant women who had previously undergone Roux-en-Y gastric bypass (RYGB), correlating these measures with anthropometric maternal characteristics and perinatal outcomes. METHODS: An analytical prospective longitudinal study was conducted at a clinic in Rio de Janeiro, Brazil, between March 3, 2008, and March 30, 2012, among women with singleton pregnancies who had previously undergone RYGB. Participants received daily oral supplementation with 5000 IU retinol and 15 mg zinc. Variables assessed included vitamin A status (serum retinol and beta-carotene; gestational night blindness), serum zinc concentration, maternal anthropometry, complications during pregnancy, and perinatal outcomes. RESULTS: Overall, 30 women participated. In all trimesters, more than 60% had inadequate serum levels of retinol or beta-carotene. Night blindness was reported by 17 (57%) women in each trimester. Only 6 (20%) women had zinc inadequacy in the first and third trimesters. No significant association was observed between serum retinol or zinc and maternal anthropometry and birth weight. Vitamin A deficiency was associated with urinary tract infection (first trimester, P=0.020) and dumping syndrome (third trimester, P=0.013). CONCLUSION: Despite RYGB and nutritional deficiencies (especially of vitamin A and zinc) increasing risks during pregnancy, there was no apparent fetal compromise when considering the analysis of birth weight and length of pregnancy at birth. PMID- 26868068 TI - The evaluation of uterine artery embolization as a nonsurgical treatment option for adenomyosis. AB - OBJECTIVE: To evaluate the safety and efficacy of uterine artery embolization (UAE) for the treatment of adenomyosis. METHODS: A prospective study was performed at Yuhuangding Hospital, China, between January 2012 and December 2013, enrolling premenopausal patients diagnosed with adenomyosis. All patients were treated with bilateral UAE using 500-700-MUm tris-acryl gelatin microspheres. At baseline, and 3, 6, and 12months after UAE, magnetic resonance imaging was used to assess uterine volume and patient-assessed improvements in dysmenorrhea were recorded. Any complications and adverse events were reported. RESULTS: In total, 117 patients with adenomyosis were enrolled. The bilateral UAE procedure was successful in 115 (98.3%) patients, who were able to return to normal activity within 1week of treatment. At 12-month follow-up, a median 51.0% reduction in uterine volume from baseline was recorded (P=0.005). Marked and moderate improvements in dysmenorrhea symptoms were reported by 64 (55.7%) and 31 (27.0%) participants, respectively. Pelvic pain of varying intensity was reported by 112 (97.4%) patients but was managed with analgesia. Persistent amenorrhea was experienced by 2 (1.7%) individuals following treatment. Patients did not encounter any new gynecologic or general complications following UAE treatment. CONCLUSION: UAE could be considered as a minimally invasive treatment option for patients with adenomyosis. Further research to compare the efficacy and safety of UAE with conventional hysterectomy is warranted. PMID- 26868069 TI - Lymph node micrometastases in initial stage cervical cancer and tumoral recurrence. AB - OBJECTIVE: To evaluate the prevalence of micrometastases in lymph node tissue of patients with stage Ib1-IIA cervical cancer, the correlation of micrometastases with tumor recurrence and survival, and the expression of D2-40 in the primary tumor of patients with recurrence and/or micrometastases and its correlation with histopathologic findings. METHODS: In a retrospective study, the medical records of all patients with cervical cancer treated at a hospital in Sao Paulo, Brazil, between 2001 and 2007 were reviewed. Patients with no lymph node metastases and treated with radical hysterectomy without adjuvant treatment were included. Tumor sections were reviewed and lymph nodes were analyzed with AE1/AE3. Patients with and without recurrence were compared. The presence of lymph node micrometastasis or isolated tumor cells was also evaluated. RESULTS: Of the 83 patients evaluated, 15 (18%) had recurrence. Significant differences between patients with and without recurrence were observed with regard to tumor greatest axis, clinical stage, number of micrometastases, and negative lymph nodes (P<=0.04). Lymph node micrometastases and isolated tumor cells were significantly different for a stromal invasion depth greater than 2/3 (P=0.046). CONCLUSION: The presence of lymph node micrometastases is an important risk factor for tumor recurrence. These patients should be considered eligible for adjuvant radiochemotherapy treatment. PMID- 26868070 TI - Validation of a structured intensive laparoscopic course for basic and advanced gynecologic skills training. AB - OBJECTIVE: To describe and validate a gynecologic laparoscopic-surgery training model. METHODS: The present prospective observational study was conducted at the Minimally Invasive Surgery Centre Jesus Uson, Caceres, Spain, between January 2011 and June 2013. Novice gynecologists attended a 3-day course including simulation and animal training. Participants' were assessed before and after training using a virtual reality simulator; during training, gynecologists were timed and assessed using an Objective and Structured Assessment of Technical Skills score. The virtual reality simulator-assessed skills were eye-hand coordination, hand-hand coordination, and transference of objects. Participants were asked to rate various elements of the training program using a five-point scale. RESULTS: The study enrolled 21 gynecologists. Participants performed all tasks faster (P<0.001), using fewer movements (P<0.05 for left and right instruments), after receiving training. During participants' final animal and simulator training sessions, completion times were reduced (P<0.001) and assessment scores (P<0.001) increased for all techniques and tasks. Participants considered suturing to be the most useful aspect of the basic-skills training (4.95+/-0.22); animal training received a higher rating than simulator training for practicing new techniques (4.81+/-0.40 vs 4.05+/-0.86) and maintaining skills (4.76+/-0.54 vs 3.95+/-0.97). CONCLUSION: Combining proficiency-based physical simulation and animal training models under expert guidance is an efficient model for improving basic and advanced laparoscopic skills. Suturing and animal models were the preferred training components. PMID- 26868071 TI - Progestin-based contraceptive on the same day as medical abortion. AB - OBJECTIVE: To determine the success rate of medical abortion when a progestin based contraceptive-either an etonogestrel implant or depot medroxyprogesterone acetate (DMPA) injection-is given on the same day as mifepristone for medical abortion. METHODS: In a retrospective chart review, data were assessed for women aged 15-49years who underwent medical abortion (<=63days of pregnancy) at two hospitals in KwaZulu Natal, South Africa, between August 2013 and July 2014. The women were given oral mifepristone (200mg) and buccal misoprostol (800MUg), and received an etonogestrel implant or DMPA injection on the same day as mifepristone. The primary outcome was the success rate of medical abortion. Comparative data were obtained through a PubMed search. RESULTS: A total of 89 women were included. Complete termination was achieved in 87 (98%, 95% confidence interval 95%-100%) women. This success rate is similar to that reported in a previous systematic review of the rate of medical abortion success without progestin contraceptive administration (94.8%). CONCLUSIONS: Administration of a progestin-based contraceptive such as an etonogestrel implant or DMPA injection on the same day as mifepristone for medical abortion did not alter the success rates. PMID- 26868072 TI - Association between bone mineral density and metabolic syndrome in Turkish women who were postmenopausal. AB - OBJECTIVE: To investigate the relationship between the parameters of metabolic syndrome and bone mineral density (BMD) at the femoral neck and lumbar spine in Turkish women who were postmenopausal. METHODS: In a retrospective study, the records of patients who were postmenopausal attending the Menopause Outpatient Clinic of a tertiary women's hospital in Ankara, Turkey, between January 1, 2014 and December 31, 2014 were retrieved. Patient's BMD at the lumbar spine and femoral neck were assessed using T-scores, and parameters of metabolic syndrome were evaluated in all patients. RESULTS: The records of 315 patients were retrieved. The mean age of patients was 55.63+/-6.14years (range 45-71 years). Metabolic syndrome was recorded in 92 (29.2%) patients. Following adjustment for age, patients with metabolic syndrome had higher T-scores at the femoral neck than patients without metabolic syndrome (-0.67+/-0.1 vs -1.15+/-0.06; P=0.001); there was no significant difference in T-scores at the lumbar spine (P=0.062). A Spearman correlation analysis of the entire study cohort demonstrated a negative association between high-density lipoprotein cholesterol and BMD at the lumbar spine and femoral neck (r=-0.12 and r=-0.15, respectively). CONCLUSION: Metabolic syndrome could have been partly associated with increased BMD in Turkish women who were postmenopausal. PMID- 26868073 TI - The effects of previous cesarean deliveries on severe maternal and adverse perinatal outcomes at a university hospital in Tanzania. AB - OBJECTIVE: To investigate if multiparous individuals who had undergone a previous cesarean delivery experienced an increased risk of severe maternal outcomes or adverse perinatal outcomes compared with multiparous individuals who had undergone previous vaginal deliveries. METHODS: An analytical cross-sectional study at a university hospital in Dar es Salaam, Tanzania, enrolled multiparous participants of at least 28weeks of pregnancy between February 1 and June 30, 2012 . Data were collected from patients' medical records and the hospital's obstetric database. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to compare outcomes among patients who had or had not undergone previous cesarean deliveries. RESULTS: A total of 2478 patients were enrolled. A previous cesarean delivery resulted in no increase in the risk of severe maternal outcomes (OR 0.86, 95% CI 0.58-1.26; P=0.46), and decreased risk of stillbirth (OR 0.42, 95% CI 0.29-0.62, P<0.001), and intrapartum stillbirth and neonatal distress (OR 0.58, 95% CI 0.38-0.87, P=0.007). CONCLUSION: Previous cesarean delivery was not a risk factor for severe maternal outcomes or adverse perinatal outcomes. The present study was conducted at a referral institution, where individuals with previous cesarean deliveries may constitute a healthy group. Additionally, there could be differences between the study groups in terms of healthcare-seeking behavior, referral mechanisms, intrapartum monitoring, and clinical decision making. PMID- 26868074 TI - Randomized controlled trial of elevation of the fetal head with a fetal pillow during cesarean delivery at full cervical dilatation. AB - OBJECTIVE: To evaluate whether use of the Fetal Pillow (Safe Obstetric Systems, Shenfield, UK) affects maternal and fetal morbidity in cesarean delivery at full cervical dilatation. METHODS: A randomized controlled trial was conducted at two teaching hospitals in West Bengal, India, between April 1, 2013, and March 31, 2014. Women undergoing cesarean delivery at full dilatation were enrolled and randomly assigned with computer-generated random numbers (block size 10) to undergo delivery with or without the Fetal Pillow. Group assignment was not masked. The primary outcome was the incidence of major uterine wound extensions (grade 2-3). RESULTS: Overall, 120 women were assigned to each group. Major uterine wound extensions occurred in 6 (5.0%) women in the Fetal Pillow group and 39 (32.5%) in the control group (relative risk 0.23, 95% confidence interval 0.11 0.48). CONCLUSION: Use of the Fetal Pillow in second-stage cesarean delivery significantly reduces the risk of a major extension of the uterine incision. CTRI registration number: CTRI/2015/03/005651. PMID- 26868075 TI - Ductus venosus blood flow velocity waveforms during the early second trimester of pregnancy in a Thai population. AB - OBJECTIVE: To establish reference ranges for ductus venosus (DV) blood flow velocities and indices during the early second trimester. METHODS: A cross sectional DV Doppler study of fetuses at 15-22 weeks of gestation was conducted at Songklanagarind Hospital, Songkhla, Thailand, during 2013-2014. The peak forward velocities were recorded and the DV indices were calculated. Predicted reference ranges based on the 5th and 95th percentiles according to the week of gestation were constructed. RESULTS: Among 371 fetuses, measurement of DV Doppler waveforms in the sagittal plane was achieved in 97.5% of cases. With advancing pregnancy (weeks 15 to 22), the DV velocities during ventricular systole, early diastole, and atrial contraction increased from 47.48 cm/s to 68.22 cm/s, 42.23 cm/s to 60.52 cm/s, and 15.94 cm/s to 34.84 cm/s, respectively. The time-averaged maximum value increased from 37.61 cm/s to 55.42 cm/s. The DV indices-pulsatility index for the vein, peak velocity index for the vein, preload index, and systolic/a-wave ratio-decreased from 0.79 to 0.59, 0.71 to 0.53, 0.63 to 0.47, and 2.72 to 1.90, respectively. The systolic/diastolic ratio remained relatively constant at 1.12. CONCLUSIONS: Normal reference ranges for DV flow velocities and indices during the early second trimester were established. PMID- 26868076 TI - Human Factors Approach to Comparative Usability of Hospital Manual Defibrillators. AB - INTRODUCTION: Equipment-related issues have recently been cited as a significant contributor to the suboptimal outcomes of resuscitation management. A systematic evaluation of the human-device interface was undertaken to evaluate the intuitive nature of three different defibrillators. Devices tested were the Physio-Control LifePak 15, the Zoll R Series Plus, and the Philips MRx. METHODS: A convenience sample of 73 multidisciplinary health care providers from 5 different hospitals participated in this study. All subjects' performances were evaluated without any training on the devices being studied to assess the intuitiveness of the user interface to perform the functions of delivering an Automated External Defibrillator (AED) shock, a manual defibrillation, pacing to achieve 100% capture, and synchronized cardioversion on a rhythm simulator. RESULTS: Times to deliver an AED shock were fastest with the Zoll, whereas the Philips had the fastest times to deliver a manual defibrillation. Subjects took the least time to attain 100% capture for pacing with the Physio-Control device. No differences in performance times were seen with synchronized cardioversion among the devices. Human factors issues uncovered during this study included a preference for knobs over soft keys and a desire for clarity in control panel design. This study demonstrated no clearly superior defibrillator, as each of the models exhibited strengths in different areas. When asked their defibrillator preference, 67% of subjects chose the Philips. CONCLUSIONS: This comparison of user interfaces of defibrillators in simulated situations allows the assessment of usability that can provide manufacturers and educators with feedback about defibrillator implementation for these critical care devices. PMID- 26868077 TI - Representativity and co-morbidity: Two factors of importance when reporting health status among survivors of cardiac arrest. AB - AIM: Reports on differences between respondents and non-respondents of out-of hospital cardiac arrest (OHCA) survivors are sparse. This study compares respondents with non-respondents in a follow-up study of a consecutive sample of OHCA survivors and describes the relation between respondents' self-reported morbidity and health. METHODS/DESIGN: Questionnaires were administered within 12 months after the OHCA. The study population was adult patients who had survived an OHCA during 2008 to 2011, with a cerebral performance score of <=2 at discharge. The patients were identified through the Swedish registry of OHCA. The Self-administered comorbidity questionnaire and EQ VAS (Euroqol questionnaire visual analogue scale) was used to measure morbidity and health status. RESULTS: Of 298 survivors, 224 were eligible for the study and 127 responded. Mean time from cardiac arrest (CA) to follow up was 178 days. Comparing the 127 respondents with the 97 lost to follow-up and non-respondents, no significant differences were found in terms of age, sex, factors at resuscitation and in-hospital interventions. The EQ VAS median was 75 (25th,75th percentile 60,80)). Self-rated health differed between respondents reporting 0-2 conditions (n=68) and respondents reporting more than two (n=43), median EQ VAS 78 (68,90) and 65 (50,80)), respectively; p-value 0.0001. CONCLUSIONS: Despite a limited response rate, representativeness in terms of patient characteristics among survivors of OHCA with an acceptable cerebral function is achievable. A considerable proportion of the survivors lived with the burden of multi-morbidity which worsened health. PMID- 26868078 TI - Towards interventional trials on the use of oxygen during and after cardiac arrest. PMID- 26868079 TI - Kids save lives: a six-year longitudinal study of schoolchildren learning cardiopulmonary resuscitation: Who should do the teaching and will the effects last? AB - AIMS: This prospective longitudinal study over 6 years compared schoolteachers and emergency physicians as resuscitation trainers for schoolchildren. It also investigated whether pupils who were trained annually for 3 years retain their resuscitation skills after the end of this study. METHODS: A total of 261 pupils (fifth grade) at two German grammar schools received resuscitation training by trained teachers or by emergency physicians. The annual training events stopped after 3 years in one group and continued for 6 years in a second group. We measured knowledge about resuscitation (questionnaire), chest compression rate (min(-1)), chest compression depth (mm), ventilation rate (min(-1)), ventilation volume (mL), self-efficacy (questionnaire). Their performance was evaluated after 1, 3 and 6 years. RESULTS: The training events increased the pupils' knowledge and practical skills. When trained by teachers, the pupils achieved better results for knowledge (92.86% +/- 8.38 vs. 90.10% +/- 8.63, P=0.04) and ventilation rate (4.84/min +/- 4.05 vs. 3.76/min +/- 2.37, P=0.04) than when they were trained by emergency physicians. There were no differences with regard to chest compression rate, depth, ventilation volume, or self-efficacy at the end of the study. Knowledge and skills after 6 years were equivalent in the group with 6 years training compared with 3 years training. CONCLUSIONS: Trained teachers can provide adequate resuscitation training in schools. Health-care professionals are not mandatory for CPR training (easier for schools to implement resuscitation training). The final evaluation after 6 years showed that resuscitation skills are retained even when training is interrupted for 3 years. PMID- 26868080 TI - Induction of humoral immune response against Pseudomonas aeruginosa flagellin(1 161) using gold nanoparticles as an adjuvant. AB - Flagellin of Pseudomonas aeruginosa is an important vaccine candidate. N-terminal domains are highly conserved in both type a and type b flagellins. The efficacy of gold nanoparticles (AuNPs) conjugated to N-terminal domains of P. aeruginosa flagellin (flagellin(1-161)), as an immunogen in mice, has been assessed. The nanoparticles were conjugated to the recombinant protein through direct interaction of thiol molecules of the cysteines with AuNPs and formation of AuS bond. Flagellin(1-161), AuNP-flagellin(1-161), and flagellin(1-161) emulsified in Freund's adjuvant (FA: complete/incomplete Freund's adjuvant formulation) were administered subcutaneously to BALB/c mice. Mice given AuNP-flagellin(1-161) elicited high titers of anti-flagellin(1-161) antibodies compared with non-immune group and/or mice which received flagellin(1-161) without adjuvant. In whole cell ELISA, these antibodies effectively recognized the native flagellin on the bacteria. Opsonophagocytosis assay demonstrated the functional activity and specificity of anti-flagellin(1-161) antibodies raised by AuNP-flagellin(1-161) against homologous strain. All of the results were comparable with those obtained by use of FA. Taken together, this is the first report of conjugation of AuNPs to flagellin and evaluating its immune response against P. aeruginosa. PMID- 26868081 TI - Hong Kong Chinese parental attitudes towards vaccination and associated socio demographic disparities. AB - BACKGROUND: Most previous studies on parental attitudes towards vaccination focused on a disease-specific vaccine. In this study we describe general attitudes towards vaccination in Chinese parents and associated socio-demographic disparities. METHODS: Data were collected from a random sample of 1996 Hong Kong Chinese parents by telephone interviews (response rate 60%). Multiple linear regression analysis was performed. RESULTS: Most parents believed vaccination to be effective (91.6%) and beneficial (78.7%), though many considered optional vaccines unimportant (39.5%) and unnecessary (62.1%). Demographic characteristics associated with parental negative attitudes to vaccination included being female, born in Hong Kong, married, having fewer children, and children ever experienced vaccination side effects. Lower personal income and religious affiliation were associated with more hesitant attitudes towards optional vaccines. CONCLUSION: Segments of the population hold significantly negative attitudes towards vaccination and optional vaccines, suggesting a need for targeted efforts on vaccination communication in these groups. PMID- 26868082 TI - Parental report of vaccine receipt in children with autism spectrum disorder: Do rates differ by pattern of ASD onset? AB - A contentious theory espoused by some parents is that regressive-onset of autism spectrum disorder (ASD) is triggered by vaccines. If this were true, then vaccine receipt should be higher in children with regressive-onset ASD compared with other patterns of onset. Parental report of rate of receipt for six vaccines (DPT/DTaP, HepB, Hib, polio, MMR, varicella) was examined in children with ASD (N=2755) who were categorized by pattern of ASD onset (early onset, plateau, delay-plus-regression, regression). All pairwise comparisons were significantly equivalent within a 10% margin for all vaccines except varicella, for which the delay-plus-regression group had lower rates of receipt (81%) than the early-onset (87%) and regression (87%) groups. Findings do not support a connection between regressive-onset ASD and vaccines in this cohort. PMID- 26868083 TI - Vaccination with virus-like particles containing H5 antigens from three H5N1 clades protects chickens from H5N1 and H5N8 influenza viruses. AB - Highly pathogenic avian influenza (HPAI) viruses, especially H5N1 strains, represent a public health threat and cause widespread morbidity and mortality in domestic poultry. Recombinant virus-like particles (VLPs) represent a promising novel vaccine approach to control avian influenza including HPAI strains. Influenza VLPs contain viral hemagglutinin (HA), which can be expressed in cell culture within highly immunogenic VLPs that morphologically and antigenically resemble influenza virions, except VLPs are non-infectious. Here we describe a recombinant VLP containing HA proteins derived from three distinct clades of H5N1 viruses as an experimental, broadly protective H5 avian influenza vaccine. A baculovirus vector was configured to co-express the H5 genes from recent H5N1 HPAI isolates A/chicken/Germany/2014 (clade 2.3.4.4), A/chicken/West Java/Subang/29/2007 (clade 2.1.3) and A/chicken/Egypt/121/2012 (clade 2.2.1). Co expression of these genes in Sf9 cells along with influenza neuraminidase (NA) and retrovirus gag genes resulted in production of triple-clade H555 VLPs that exhibited hemagglutination activity and morphologically resembled influenza virions. Vaccination of chickens with these VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with three different viruses including the recent U.S. H5N8 HPAI isolate. We conclude that these novel triple-clade VLPs represent a feasible strategy for simultaneously evoking protective antibodies against multiple variants of H5 influenza virus. PMID- 26868084 TI - Simulating Chiral Magnetic and Separation Effects with Spin-Orbit Coupled Atomic Gases. AB - The chiral magnetic and chiral separation effects-quantum-anomaly-induced electric current and chiral current along an external magnetic field in parity odd quark-gluon plasma-have received intense studies in the community of heavy ion collision physics. We show that analogous effects occur in rotating trapped Fermi gases with Weyl-Zeeman spin-orbit coupling where the rotation plays the role of an external magnetic field. These effects can induce a mass quadrupole in the atomic cloud along the rotation axis which may be tested in future experiments. Our results suggest that the spin-orbit coupled atomic gases are potential simulators of the chiral magnetic and separation effects. PMID- 26868085 TI - Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease. AB - Interleukin-15 (IL-15) is essential for the homeostasis of lymphoid cells particularly memory CD8(+) T cells and NK cells. These cells are abundant in the liver, and are implicated in obesity-associated pathogenic processes. Here we characterized obesity-associated metabolic and cellular changes in the liver of mice lacking IL-15 or IL-15Ralpha. High fat diet-induced accumulation of lipids was diminished in the livers of mice deficient for IL-15 or IL-15Ralpha. Expression of enzymes involved in the transport of lipids in the liver showed modest differences. More strikingly, the liver tissues of IL15-KO and IL15Ralpha KO mice showed decreased expression of chemokines CCl2, CCL5 and CXCL10 and reduced infiltration of mononuclear cells. In vitro, IL-15 stimulation induced chemokine gene expression in wildtype hepatocytes, but not in IL15Ralpha deficient hepatocytes. Our results show that IL-15 is implicated in the high fat diet-induced lipid accumulation and inflammation in the liver, leading to fatty liver disease. PMID- 26868086 TI - Interleukin-27 inhibits malignant behaviors of pancreatic cancer cells by targeting M2 polarized tumor associated macrophages. AB - Pancreatic cancer is characterized as inflammatory malignancy with a dismal prognosis. There is abundant intratumoral infiltration of macrophages, and most of these tumor associated macrophages (TAM) are induced to be M2 phenotype. The M2 polarized TAM has been demonstrated to promote progression and induce chemo resistance of pancreatic cancer. Interleukin (IL)-27 is a novel member of IL-12 cytokine family and its roles in regulation of phenotypes and functions of TAM remain largely unknown. In this study, we demonstrated IL-27 significantly inhibited the M2 macrophages polarization and dampened the proliferation, migration and metastasis of pancreatic cancer cells and as well enhanced the efficacy of gemcitabine. IL-27 could be potential to improve the treatment of pancreatic cancer by targeting M2 polarized TAMs. PMID- 26868087 TI - Secretion of cytokines and heat shock protein (HspA1A) by ovarian cancer cells depending on the tumor type and stage of disease. AB - Epithelial ovarian cancer is a heterogeneous disease comprising several tumor types that each have multiple histopathological features and different biological behaviors. Recent morphologic and molecular genetic studies have allowed for the categorization of various types of ovarian cancer into two groups: type I and type II. Type I tumors are low-grade and are genetically more stable, while type II tumors are high-grade and genetically unstable. The determination of the type of ovarian cancer may have implications in terms of the appropriate therapeutic strategy because different prognoses and responses to chemotherapeutic agents are observed. Therefore, the current challenge is better recognition of the features of cancer cells, which may result in more individualized therapy. The aim of the current studies was to compare the ability of ovarian cancer cells isolated from tumors, which were classified as type I or type II ovarian cancer, to release pro inflammatory and immunosuppressive cytokines and heat shock protein (HspA1A). These factors are known to facilitate tumor cell survival, invasion and metastasis. Our studies demonstrated that ovarian cancer cells isolated from patients with type II tumors released high levels of immunosuppressive cytokines (i.e., interleukin 10 and transforming growth factor beta) and HspA1A in vitro. Conversely, ovarian cancer cells obtained from of type I tumors were significantly less active. We did not observe any difference in the ability of the isolated cancer cells to secrete pro-inflammatory cytokines, regardless of the type of ovarian cancer. In this study, we found that cancer cells from patients with type II tumors demonstrated more intense activity in regards to survival and metastasis, which should be considered during therapy. PMID- 26868088 TI - Effects of tumor vaccine expressing Granulocyte-Macrophage Colony Stimulating Factor and interleukin-18 fusion on cancer cells and its possible application for cancer immunotherapy. AB - To access antitumor effects of a combined Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and interleukin-18 (IL-18), cDNA fusion of murine GM CSF and mature IL-18 (GMIL-18) was constructed and transfected in mammalian cells. GMIL-18 fusion protein was highly secreted and displayed bifunctional activities, possessing immune response initiation and cytokine roles, including IFN-gamma induction in mouse splenocytes and increased proliferation of GM-CSF dependent cells, M-NSF-60. The GMIL-18 secreting tumor vaccine was generated and it strongly stimulated differentiation of dendrite cells (DCs) and effusive CD8+ and CD4+ cell infiltration into tumor mice. Moreover, growth of CT26 mouse colon cancer cells was significantly retarded by GMIL-18 (CT26GMIL-18), but not by CT26GM-CSF- or CT26IL-18. The efficiency of prophylactic vaccination was greater than that of therapeutic vaccination in terms of tumor size and its inhibitory role in proliferation. In micrometastasis analysis of tumor models, gamma-ray irradiated GMIL-18 tumor vaccine showed a smaller number of liver-meta tumor nodules in mouse liver cells. We concluded that bifunctional GMIL-18 fusion protein could be applied as an immune therapy for cancer treatments. PMID- 26868089 TI - Chylomicrons: Advances in biology, pathology, laboratory testing, and therapeutics. AB - The adequate absorption of lipids is essential for all mammalian species due to their inability to synthesize some essential fatty acids and fat-soluble vitamins. Chylomicrons (CMs) are large, triglyceride-rich lipoproteins that are produced in intestinal enterocytes in response to fat ingestion, which function to transport the ingested lipids to different tissues. In addition to the contribution of CMs to postprandial lipemia, their remnants, the degradation products following lipolysis by lipoprotein lipase, are linked to cardiovascular disease. In this review, we will focus on the structure-function and metabolism of CMs. Second, we will analyze the impact of gene defects reported to affect CM metabolism and, also, the role of CMs in other pathologies, such as atherothrombotic cardiovascular disease and diabetes mellitus. Third, we will provide an overview of the laboratory tests currently used to study CM disorders, and, finally, we will highlight current treatments in diseases affecting CMs. PMID- 26868091 TI - IS THE LINK BETWEEN HEALTH AND WEALTH CONSIDERED IN DECISION MAKING? RESULTS FROM A QUALITATIVE STUDY. AB - OBJECTIVES: The aim of this study was to explore whether wealth effects of health interventions, including productivity gains and savings in other sectors, are considered in resource allocations by health technology assessment (HTA) agencies and government departments. To analyze reasons for including, or not including, wealth effects. METHODS: Semi-structured interviews with decision makers and academic experts in eight countries (Australia, France, Germany, Italy, Poland, South Korea, Sweden, and the United Kingdom). RESULTS: There is evidence suggesting that health interventions can produce economic gains for patients and national economies. However, we found that the link between health and wealth does not influence decision making in any country with the exception of Sweden. This is due to a combination of factors, including system fragmentation, methodological issues, and the economic recession forcing national governments to focus on short-term measures. CONCLUSIONS: In countries with established HTA processes and methods allowing, in principle, the inclusion of wider effects in exceptional cases or secondary analyses, it might be possible to overcome the methodological and practical barriers and see a more systematic consideration of wealth effect in decision making. This would be consistent with principles of efficient priority setting. Barriers for the consideration of wealth effects in government decision making are more fundamental, due to an enduring separation of budgets within the public sector and current financial pressures. However, governments should consider all relevant effects from public investments, including healthcare, even when benefits can only be captured in the medium- and long-term. This will ensure that resources are allocated where they bring the best returns. PMID- 26868092 TI - ParkIndex: Development of a standardized metric of park access for research and planning. AB - OBJECTIVE: A lack of comprehensive and standardized metrics for measuring park exposure limits park-related research and health promotion efforts. This study aimed to develop and demonstrate an empirically-derived and spatially-represented index of park access (ParkIndex) that would allow researchers, planners, and citizens to evaluate the potential for park use for a given area. METHODS: Data used for developing ParkIndex were collected in 2010 in Kansas City, Missouri (KCMO). Adult study participants (n=891) reported whether they used a park within the past month, and all parks in KCMO were mapped and audited using ArcGIS 9.3 and the Community Park Audit Tool. Four park summary variables - distance to nearest park, and the number of parks, amount of park space, and average park quality index within 1mile were analyzed in relation to park use using logistic regression. Coefficients for significant park summary variables were used to create a raster surface (ParkIndex) representing the probability of park use for all 100m*100m cells in KCMO. RESULTS: Two park summary variables were positively associated with park use - the number of parks and the average park quality index within 1 mile. The ParkIndex probability of park use across all cells in KCMO ranged from 17 to 77 out of 100. CONCLUSION: ParkIndex represents a standardized metric of park access that combines elements of both park availability and quality, which was developed empirically and can be represented spatially. This tool has both practical and conceptual significance for researchers and professionals in diverse disciplines. PMID- 26868090 TI - DNA Polymerases eta and zeta Combine to Bypass O(2)-[4-(3-Pyridyl)-4 oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens. AB - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are important human carcinogens in tobacco products. They are metabolized to produce a variety 4-(3-pyridyl)-4-oxobutyl (POB) DNA adducts including O(2)-[4 (3-pyridyl)-4-oxobut-1-yl]thymidine (O(2)-POB-dT), the most abundant POB adduct in NNK- and NNN-treated rodents. To evaluate the mutagenic properties of O(2)-POB dT, we measured the rate of insertion of dNTPs opposite and extension past O(2) POB-dT and O(2)-Me-dT by purified human DNA polymerases eta, kappa, iota, and yeast polymerase zeta in vitro. Under conditions of polymerase in excess, polymerase eta was most effective at the insertion of dNTPs opposite O(2)-alkyl dTs. The time courses were biphasic suggesting the formation of inactive DNA polymerase complexes. The kpol parameter was reduced approximately 100-fold in the presence of the adduct for pol eta, kappa, and iota. Pol eta was the most reactive polymerase for the adducts due to a higher burst amplitude. For all three polymerases, the nucleotide preference was dATP > dTTP ? dGTP and dCTP. Yeast pol zeta was most effective in bypassing the adducts; the kcat/Km values were reduced only 3-fold in the presence of the adducts. The identity of the nucleotide opposite the O(2)-alkyl-dT did not significantly affect the ability of pol zeta to bypass the adducts. The data support a model in which pol eta inserts ATP or dTTP opposite O(2)-POB-dT, and then, pol zeta extends past the adduct. PMID- 26868095 TI - The relevance of Foucault and Bourdieu for medical anthropology: exploring new sites. PMID- 26868093 TI - Trends and predictors of HPV vaccination among U.S. College women and men. AB - BACKGROUND: HPV vaccination was recommended by the Advisory Committee on Immunization Practices for young adult females in 2006 and males in 2011 to prevent HPV-related cancers and genital warts. As this prevention mechanism continues to disseminate, it is necessary to monitor the uptake of this vaccine. College students represent an important population for HPV vaccination efforts and surveillance due to increased risk for HPV infection and representing a priority population for catch-up HPV vaccination. The purpose of this study was to assess the trends in HPV vaccination among U.S. college females and males from 2009 to 2013, and to examine whether predictors for HPV vaccination differ between males and females. METHODS: The National College Health Assessment-II (Fall 2009-2013) was used to assess trends in HPV vaccination using hierarchical logistic regression across genders and demographics. Data from 2013 were used to assess demographic variables associated with HPV vaccination for males and females, respectively. The analysis was conducted in 2015. RESULTS: Females had nearly double the rates of HPV vaccination compared to males over time. All demographic sub-groups had significant increases in vaccine rates over time, with select male sub-groups having more accelerated increases (e.g., gay). Young age (18-21 vs. 22-26years) was a significant predictor for HPV vaccination among males and females, while race/ethnicity was a predictor of vaccination among females only. CONCLUSIONS: These findings identified specific demographic sub groups that need continued support for HPV vaccination. Campus health centers may be rational settings to facilitate clinical opportunities for HPV vaccination among unvaccinated college students. PMID- 26868094 TI - Ultrastrong Bioinspired Graphene-Based Fibers via Synergistic Toughening. AB - Ultrastrong bioinspired graphene-based fibers are designed and prepared via synergistic toughening of ionic and covalent bonding. The tensile strength reaches up to 842.6 MPa and is superior to all other reported graphene-based fibers. In addition, its electrical conductivity is as high as 292.4 S cm(-1). This bioinspired synergistic toughening strategy supplies new insight toward the construction of integrated high-performance graphene-based fibers in the near future. PMID- 26868096 TI - Resources for health in Uganda: Bourdieu's concepts of capital and habitus. AB - Based on long-term fieldwork in rural Eastern Uganda, this paper explores the use of Bourdieu's concepts of capital and habitus to analyse local understandings of resources and strategies for health. In this local Ugandan context health cannot be taken for granted, but requires persistent effort. In local terms, health is broadly described as having a 'good life' and this is experienced as a social achievement conditioned by access to a variety of human and material resources. Wealth, unity with others, learnedness, 'smartness', and bodily strength are described by local people as key resources for a 'good life'. Bourdieu's concepts of economic, social, cultural and symbolic capital are applied in discussing the dynamics of how these local resources are converted into different forms of capital in the quest for health. It is argued that in order to more fully analyse how people think about, and strive for, health, a concept of bodily capital may be a useful addition to Bourdieu's original forms of capital. PMID- 26868097 TI - Therapeutic itineraries: the medical field in rural Burkina Faso. AB - The health care system in Burkina Faso presents a paradox. The number of health centres in the rural areas has increased significantly since the signing of the Alma-Ata Declaration in 1978. However, studies show that these public health facilities are grossly under-utilized. Parallel to this development, local healers of different types are numerous and popular, and self-treatment extremely common. The present study explores this paradox on the basis of fieldwork in three villages in south-east Burkina Faso. Drawing on Bourdieu's notions of field and capital, the local health care system is analysed as a medical field where the different types of healers and health care institutions position themselves and are positioned through villagers' choice of therapy in their health seeking processes. The popularity of self-medication and various types of local healers are discussed in relation to the strengths of the various forms of capital in the medical field. It is argued that both local social relationships and indigenous knowledge are important variables in this particular area and add to our understanding of the low utilization rate of the public health facilities. PMID- 26868098 TI - Medicalization and morality in a weak state: health, hygiene and water in Dar Es Salaam, Tanzania. AB - Inspired by Foucault, many studies have examined the medicalization of everyday life in Western societies. This paper reconsiders potentials and limitations of this concept in an African city. Grounded in ethnographic research in Dar es Salaam, Tanzania, it concentrates on cleanliness, health and water in a lower middle-class neighbourhood. The findings show that women are familiar with professional health development discourses emphasizing cleanliness as a high value linked to bodily and domestic health. These discourses have been diffused in schools, clinics and other institutions during the colonial and socialist period. Women not only refer to these discourses, they try to reproduce them in daily practice and even demand them. This coercive yet voluntary nature of institutionalized discourses points to 'paradoxes of medicalization' also found in Western societies. It acquires, however, different meanings in a weak state like contemporary Tanzania which hardly manages to institutionalize medicalization through professional practice. Under such conditions, women who choose to follow health development discourses suffer a heavier practical, intellectual and emotional burden than those who are less committed. This may at least partly explain why many women assume a pragmatic stance towards the medicalization of everyday life. PMID- 26868099 TI - Pleasure, power and dangerous substances: applying Foucault to the study of 'heroin dependence' in Germany. AB - Taking the observation of disciplining and controlling everyday practices of methadone substitution as a point of departure, this paper explores the question of what exactly is so threatening or dangerous about heroin and heroin users. Drawing on the work of Michel Foucault and Judith Butler, the main argument of this article is that the danger of heroin use is a discursive construction in accordance with bio-power. On the one hand, the juridical governance of heroin dependence is shifting from punishment to therapy, and biomedical discourses proclaim the substitution of a moral notion of heroin dependence by a disease model. Nevertheless, in the context of the anxiety associated with HIV, heroin remains the dangerous drug par excellence, and heroin users are constructed as 'abject others', unable to subordinate to certain social norms. As a reaction to such injurious ascriptions, I argue, applicants to the methadone programme in their life stories intensely narrate a desire for normalization, which I read as a desire to emerge from the realm of the abject. Both the danger and the pleasure associated with heroin use are bound to fundamental processes of subject formation, which are often ignored in biomedical and anthropological discourses. PMID- 26868100 TI - Bodily sovereignty as political sovereignty: 'self-care' in Kolkata, India. AB - This paper explores the potentials of applying Michel Foucault's notion of 'self care' to issues in medical anthropology. While Foucault's writings on regimes of power/knowledge have had an enormous influence on medical anthropologists, his late works on the ethics of the self have not yet received much attention. This paper discusses Foucault's notion of self-care in relation to Ayurvedic interpretations of digestion in Kolkata (formerly Calcutta, India). In Kolkata, it is a widely held belief that attentive care of the self, and especially for the stomach, can set a person free from dependencies. Yet at the same time, 'modern' people are seen as unable to live up to the ethics of self-care. The parallel between bodily sovereignty and cultural/political sovereignty produces a discourse on 'lack of self-control' as one of the main reasons for continuing dependency in all spheres of life. How does Foucault's late work help to conceptualize these findings? PMID- 26868101 TI - French colonial medicine in Cambodia: reflections of governmentality. AB - Studies of colonial medicine, mostly from former British colonies, have shown that colonial medical interventions mostly benefited the European colonisers and often had very little positive effects on the health of the native populations at large. A common assumption is that this was also the case for French colonial medicine in general, and for colonial medicine in Cambodia in particular, and that the unsatisfactory contemporary state of the medical services in the country may be partly explained by its colonial past. As a way to test this assumption, this paper presents an ethnography of colonial medicine in Cambodia in the first decades of the twentieth century. Documents in the Cambodian National Archives provided the primary sources, and their significance was assessed against the background of the authors' experience of medical anthropological research in contemporary Cambodia. Michel Foucault's concept of governmentality is used as the interpretative frame. Elements of colonial governmentality in the medical field included the promotion of modern medicine through the free dispensing of medicines and medical treatment and rudimentary medical training of members of the local population, as well as compulsory vaccinations and surveillance of the colonial subjects. It is concluded that both the idea of medicine as a 'tool of empire' and that of the colonial physician as a humanitarian hero are equally incomplete as general descriptions, and that specific ethnographies of medical policies and practices should be undertaken for particular colonial settings. This paper provides the first anthropological account of colonial medicine in Cambodia. PMID- 26868102 TI - Addressing Skyrocketing Cancer Drug Prices Comes With Tradeoffs: Pick Your Poison. PMID- 26868103 TI - Ecological interactions and the fitness effect of water-use efficiency: Competition and drought alter the impact of natural MPK12 alleles in Arabidopsis. AB - The presence of substantial genetic variation for water-use efficiency (WUE) suggests that natural selection plays a role in maintaining alleles that affect WUE. Soil water deficit can reduce plant survival, and is likely to impose selection to increase WUE, whereas competition for resources may select for decreased WUE to ensure water acquisition. We tested the fitness consequences of natural allelic variation in a single gene (MPK12) that influences WUE in Arabidopsis, using transgenic lines contrasting in MPK12 alleles, under four treatments; drought/competition, drought/no competition, well watered/competition, well-watered/no competition. Results revealed an allele * environment interaction: Low WUE plants performed better in competition, resulting from increased resource consumption. Contrastingly, high WUE individuals performed better in no competition, irrespective of water availability, presumably from enhanced water conservation and nitrogen acquisition. Our findings suggest that selection can influence MPK12 evolution, and represents the first assessment of plant fitness resulting from natural allelic variation at a single locus affecting WUE. PMID- 26868104 TI - Solitude: On Dining Alone, Cellphones, and Teddy Bears. PMID- 26868105 TI - Structure of iridoid synthase in complex with NADP(+)/8-oxogeranial reveals the structural basis of its substrate specificity. AB - Iridoid synthase (IS), as a vegetal enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily, produces the ring skeletons for downstream alkaloids with various pharmaceutical activities, including the commercially available antineoplastic agents, vinblastine and vincristine. Here, we present the crystal structures of IS in apo state and in complex with NADP(+)/8-oxogeranial, exhibiting an active center that lacks the classical Tyr/Lys/Ser triad spatially conserved in SDRs, with only the catalytically critical function of triad tyrosine remained in Tyr178. In consistent, mutation of Tyr178 to a phenylalanine residue significantly abolished the catalytic activity of IS. Within the substrate binding pocket, the linear-shaped 8 oxogeranial adopts an entirely extended conformation with its two aldehyde ends hydrogen-bonded to Tyr178-OH and Ser349-OH, respectively. In addition, the intermediate carbon chain of bound substrate is harbored by a well-ordered hydrophobic scaffold, involving residues Ile145, Phe149, Leu203, Met213, Phe342, Ile345 and Leu352. Mutagenesis studies showed that both Ser349 and the hydrophobic residues around are determinant to the substrate specificity and, consequently, the catalytic activity of IS. In contrast, the Gly150-Pro160 loop previously proposed as a factor involved in substrate binding might have very limited contribution, because the deletion of residues Ile151-His161 has only slight influence on the catalytic activity. We believe that the present work will help to elucidate the substrate specificity of IS and to integrate its detailed catalytic mechanism. PMID- 26868106 TI - Compaction of isolated Escherichia coli nucleoids: Polymer and H-NS protein synergetics. AB - Escherichia coli nucleoids were compacted by the inert polymer polyethylene glycol (PEG) in the presence of the H-NS protein. The protein by itself appears to have little impact on the size of the nucleoids as determined by fluorescent microscopy. However, it has a significant impact on the nucleoidal collapse by PEG. This is quantitatively explained by assuming the H-NS protein enhances the effective diameter of the DNA helix leading to an increase in the depletion forces induced by the PEG. Ultimately, however, the free energy of the nucleoid itself turns out to be independent of the H-NS concentration. This is because the enhancement of the supercoil excluded volume is negligible. The experiments on the nucleoids are corroborated by dynamic light scattering and EMSA analyses performed on DNA plasmids in the presence of PEG and H-NS. PMID- 26868107 TI - Crystal structure of truncated FlgD from the human pathogen Helicobacter pylori. AB - Flagellin component D (FlgD) participates in the assembly of flagella, helical tubular structures that provide motility in non-filamentous bacteria. FlgD guides and controls the polymerization of FlgE that builds the hook, a short curved and hollow cylinder that connects the flagellar basal body spanning the cell envelope to the protruding filament. Crystal structures of truncated forms of Helicobacter pylori FlgD from two different strains in two space groups, I422 and P2, are reported here, at 2.2A and 2.8A resolution, respectively. Analogously to Pseudomonas aeruginosa and Xanthomonas campestris FlgD proteins, crystallization experiments set up for the full length protein resulted in crystals of a truncated form, lacking both N- and C-terminus ends. The crystal structures of the central domain show that the monomer is composed of a tudor and a fibronectin type III domain. The full length HpFlgD contains a long N-terminal signal region, probably partially flexible, a central globular region and a C-terminal segment with a peculiar repetitive pattern of amino acids. The spatial orientation of the two domains in HpFlgD differs from that of the homologous FlgD family members, P. aeruginosa and X. campestris. This difference together with the observation that HpFlgD assembles into tetramers, both in the solution and in the two crystal forms, strongly suggests that significant differences exist in the molecular organization of the flagella in different bacterial species. PMID- 26868108 TI - [Core principles for the regulation of placement subject to public law in psychiatric hospitals - with explanations]. AB - While the provisions of the highest courts concerning the involuntary commitment and treatment in psychiatric hospitals of people unable to give their consent are being implemented, in many federal states corresponding adjustments to the rules governing involuntary commitment in accordance with the mental health laws and laws on involuntary commitment are still pending. In states where new regulations do exist, legal experts express doubts that they conform to the Constitution and the UN Convention on the Rights of Persons with Disabilities. The DGPPN has formulated key parameters for involuntary commitment from a clinical perspective, which should be taken into account in the new regulations of the individual federal states. PMID- 26868109 TI - [Erratum to: Should antipsychotics be used in prodromal stages of schizophrenia to prevent psychosis? Pro]. PMID- 26868110 TI - [Relatives in intensive care units: (Un)Satisfied needs]. AB - BACKGROUND: Relatives of patients in intensive care units (ICU) have important supportive care needs which are often unrecognized and rarely satisfactorily met. OBJECTIVES: Description of stress factors and strains as well as supportive care needs, assessment of care needs, empirical evidence for care needs, satisfaction of care needs, options and efficacy of psychosocial support and communication recommendations for this special situation. MATERIAL AND METHODS: Evaluation of literature review articles, discussion of basic qualitative and quantitative research findings, meta-analyses and expert recommendations. RESULTS: Relatives of ICU patients report a number of cognitive, emotional, social and pragmatic support needs. Important needs, such as maintenance of hope and security as well as sincere and needs-adjusted communication often remain unrecognized and are rarely satisfactorily met. The weighting and prioritization of support needs are modulated by sociodemographic and cultural factors. Psychoeducative interventions reduce the psychosocial distress of family members. Communicative strategies of healthcare professionals reduce the risk of posttraumatic stress disorders for family members, reduce anxiety and depression and improve participative decision making. CONCLUSION: Healthcare professionals in ICUs should be sensitized to the specific characteristics of these special situations. For healthcare professionals it is equally important to improve self-awareness regarding their own defense mechanisms and to refine communicative competence on accessibility and adequately address the reality of subjective experiences of family members. Psychosocial support services should be recommended and utilization should be encouraged. PMID- 26868111 TI - [Significance of clinical electroencephalogram in psychiatry]. AB - The generation of an electroencephalogram (EEG) provides a sensitive, non invasive and inexpensive method for the investigation of brain function. This article critically reviews the significance of EEG examinations in clinical psychiatric practice and describes relevant applications and limitations. A summary of the basic principles of the production and interpretation of an EEG is followed by a survey of typical EEG patterns in healthy subjects and pathological alterations of EEG patterns. The importance of the EEG for the clinical diagnostics of Alzheimer's disease and acute delirium as well as the differentiation between psychiatric syndromes and non-convulsive status epilepticus is reviewed. Moreover, the usefulness of the EEG is highlighted with respect to the diagnostics and monitoring of the course of lithium intoxication. Finally, this article gives a brief insight into promising research approaches that are currently being followed in modern psychiatry using an EEG. PMID- 26868112 TI - Nocardia camponoti sp. nov., an actinomycete isolated from the head of an ant (Camponotus japonicas Mayr). AB - A novel actinomycete, designated strain 1H-HV4T, was isolated from the head of Camponotus japonicas Mayr, which was collected from Northeast Agriculture University (Harbin, Heilongjiang, China). Chemotaxonomic properties of this strain were consistent with those of members of the genus Nocardia. The cell wall contained meso-diaminopimelic acid and whole-cell sugars were galactose, glucose and arabinose. The predominant menaquinone was MK-8(H4,omega-cycl). The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were identified as C18:0 10-methyl, C16:0, C18:1omega9c and C16:1omega7c. Mycolic acids were found to be present. 16S rRNA gene sequence analysis also showed that strain 1H-HV4T was a member of the genus Nocardia, with the highest sequence similarities to Nocardia salmonicida JCM 4826T (97.39%), Nocardia soli JCM 11441T (97.12%) and Nocardia cummidelens JCM 11439T (97.08%). 16S rRNA gene sequence similarities to type strains of other members of the genus Nocardia were less than 97%. However, DNA-DNA relatedness values and phenotypic data demonstrated that strain1H-HV4T was clearly distinguished from all closely related species of the genus Nocardia. It is concluded that the isolate can be classified as representing a novel species of the genus Nocardia, for which the name Nocardia camponoti is proposed. The type strain is 1H-HV4T (=DSM 100526T=CGMCC 4.7278T). PMID- 26868113 TI - Reconstruction of periacetabular tumours with saddle prosthesis or custom-made prosthesis, functional results and complications. AB - Reconstruction after resection of pelvic tumours is a major challenge. We report the outcomes and complications of 7 patients who underwent limb salvage following type II or type II, III pelvic resection and reconstruction using a saddle prosthesis or custom-made hemipelvic prosthesis. In our opinion, reconstruction using custom-made prostheses is better than placement of saddle prostheses because of a lower risk of complications and improved functional outcomes. PMID- 26868114 TI - Debridement, antibiotics and implant retention in early periprosthetic joint infection. AB - INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication in hip arthroplasty surgery. Debridement, antibiotics (AB) and implant retention (DAIR) is recommended in early PJI in association with stable implants. The aim of this study was to evaluate the success rate of DAIR in early PJI (<4 weeks) and to identify factors predicting the outcome. METHODS: This cohort study included a consecutive series of 35 patients (median age 74 years, 25 women, 26 primary arthroplasties) treated with DAIR for an early PJI in a regional hospital. RESULTS: 28 patients (80%) had their infection eradicated. DAIR-only eradicated the PJI in 22 (63%) patients with a median follow-up of 50 (24-84) months. In 17 (49%) patients, oral AB had been given prior to intraoperative cultures, which delayed first debridement with average 6 days and delayed hospital stay. Primary surgery for a hip fracture increased the risk of DAIR failure. Surgical experience did not affect the outcome. 17% (n = 6) of the patients sustained a secondary infection during their hospital stay; the majority was beta-lactam resistant coagulase negative Staphylococcus aureus. CONCLUSIONS: The success rate of DAIR was inferior to pervious controls from experienced revision centers. Hip fracture patients should be informed about the increased risk of DAIR treatment failure. In order not to delay surgery, empirically based oral AB should not be administered prior to deep cultures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02087020. PMID- 26868116 TI - Provision of total hip replacement for displaced intracapsular hip fracture and the outcomes: audit of local practice based on NICE guidelines. AB - INTRODUCTION: Hip fractures are becoming an increasing public health issue due to an ageing population (1). Total hip replacements (THR) produce better outcomes in certain patients who were functioning independently before the injury (2). We aimed to assess whether the management of intracapsular hip fracture is carried out in accordance with the National Institute for Health and Care Excellence (NICE) hip fracture guidance (1) and the outcomes with regards to performing THRs on those patients who fulfil the described criteria. METHOD: Data was collected retrospectively from the 1st April 2012 to 31st March 2013 from all fractured neck of femur patients admitted to our hospital. RESULTS: Of the 382 patients fit for an operation, 78 (20.4%) met with the NICE hip fracture guidance for a total hip replacement. Of those eligible, 32 (41.0%) did receive a THR and 4 (2.8%) patients of the 142 not eligible for a total hip replacement also received a THR. DISCUSSIONS: Of those eligible for a THR, the patients who underwent that procedure had a significantly lower mortality rate compared to those who underwent a hemiarthroplasty (0% versus 19.6% at 1 year, p = 0.007). However, those who did not meet the NICE criteria but underwent a THR had the worst mortality rate (50% at 30 days and 1 year). The provision rate of THR in displaced intracapsular hip fracture is low at 41.0% for those who met the NICE criteria. The results suggest that the decision process when determining if a patient should undergo THR for a fractured neck of femur is multifactorial. PMID- 26868115 TI - Cementless total hip arthroplasty using Biolox(r)delta ceramic-on-ceramic bearing in patients with osteonecrosis of the femoral head. AB - PURPOSE: The purpose of this study was to evaluate the results of cementless total hip arthroplasty (THA) using a 32 mm or larger Biolox(r)delta ceramic-on ceramic (CoC) bearing in patients with osteonecrosis of the femoral head after a minimum of 5 years of follow-up. MATERIALS AND METHODS: We retrospectively analysed 44 patients (53 hips) who underwent cementless THA using Biolox(r)delta CoC bearing. There were 33 men (40 hips) and 11 women (13 hips) with the mean age of 49 years. A 36 mm head was used in 42 (79%) of 53 hips and a 32 mm head was used in 11 hips with smaller acetabular shells. The mean duration of follow-up was 5.3 years (range 5-6 years). RESULTS: The mean Harris Hip Score improved from 50 points preoperatively to 97 points at final follow-up (p<0.001). All acetabular and femoral components showed radiographic evidence of osseointegration. No osteolysis was observed. No patients sustained ceramic fracture. An audible hip noise was identified in 2 (4%) of the 53 hips (1 squeaking and 1 clicking). Survivorship with revision for any reason at a minimum of 5 years was 100% in the best-case scenario and 95 % in the worst-case scenario. CONCLUSIONS: The minimum 5-year results of cementless THA using a 32 mm or larger Biolox(r)delta CoC bearing in patients with osteonecrosis of the femoral head were encouraging with excellent survivorship. However, it was also found that the risk of noise development remains even for the new alumina matrix composite ceramic. PMID- 26868117 TI - Clinical and radiographic outcomes after femoral varus derotation osteotomy for Legg-Calve-Perthes disease at 25 years follow-up: what are the determinants of outcome in the long term? AB - OBJECTIVE: The main purposes of the present study were to analyse the long-term clinical and radiographic results of femoral varus derotation osteotomy performed in a group of patients with the diagnosis of Legg-Calve-Perthes (LCP) disease and to compare the effects of age, lateral pillar classification, radiographic stage according to Waldenstrom's classification, and the amount of varisation obtained on long-term results. DESIGN: The study group consisted of 21 hips. The mean postoperative follow-up time was 25.1 years. The effect of age at the time of surgery, preoperative lateral pillar classification, Waldenstrom's classification, and the amount of varisation on Merle d'Aubigne score, Stulberg class, and presence of degenerative arthritis of the hip joint were assessed at the final follow-up. RESULTS: Better clinical and radiographic outcomes were detected in patients operated younger than 10 years. The hips with lateral pillar group C involvement preoperatively were found to be significantly associated with worse clinical scores, worse radiographic outcome, and higher rate of degenerative arthritis. The overall rate of the hips with good radiologic outcome was 52.4%. 7 hips had degenerative arthritis at the final follow-up. CONCLUSIONS: Femoral varus derotation osteotomy revealed a congruent joint in half of the operated hips and arthritis-free hip joint in 2/3 at 25 years follow-up. Age at the time of surgery and preoperative lateral pillar classification were the main determinants of the radiographic outcome whereas the factors significantly correlated with progression to degenerative arthritis were determined preoperative lateral pillar classification and Stulberg group at maturity. PMID- 26868118 TI - Dislocation after total hip replacement - there is no such thing as a safe zone for socket placement with the posterior approach. AB - INTRODUCTION: Malorientation of the socket contributes to instability after hip arthroplasty but the optimal orientation of the cup in relation to the pelvis has not been unequivocally described. Large radiological studies are few and problems occur with film standardisation, measurement methodology used and alternative definitions of describing acetabular orientation. METHODS: A cohort of 1,578 patients from a single institution is studied where all patient data was collected prospectively. Risk factors for patients undergoing surgery are analysed. Radiological data was compared between a series of non-dislocating hips and dislocating cases matched 2:1 by operation type, age and diagnosis. RESULTS: The overall dislocation rate for all 1,578 cases was 3.23% but the rate varied according to the type of surgery performed. The rate in uncomplicated primary cases was 2.4% which increased to 9.3% for second stage implantation for a two stage procedure for infection. There was no significant difference in the variability of the dislocating and non-dislocating groups for either inclination (p = 0.393) or anteversion (p = 0.661). CONCLUSIONS: A "safe zone" for socket orientation to avoid dislocation could not be defined. The cause of dislocation is multifactorial, re-establishing the anatomic centre of rotation, balancing soft tissues and avoidance of impingement around the hip are important considerations. PMID- 26868119 TI - Modular neck total hip arthroplasty - a perfect storm. AB - PURPOSE: This study was aimed to highlight neck notching as a potential cause of failure in modular neck total hip arthroplasty. It aimed to identify both the combination of modular components that place patients at greatest risk of failure and the potential mechanism for failure. METHODS: This study involved a retrospective review of 301 total hip arthroplasties (THA) using Kinectiv modular neck Technology (Zimmer, Warsaw, Indiana). The primary outcome was the presence of neck notching requiring revision. Patient records, operative notes and postoperative radiographs were reviewed. A statistical analysis was performed. RESULTS: A total of 301 THA were performed on 290 patients. There were 7 failures (2.3%). All 7 failures involved a modular combination of an anteverted neck, extended offset and length code -8 (failure rate of 36.8%, p<0.001). CONCLUSIONS: We identified femoral neck notching as a potential cause of failure in modular neck THA. The combination of an anteverted neck, extended offset and length code 8 was associated with a high rate of neck notching using the Kinectiv modular neck Technology (Zimmer, Warsaw, Indiana). Based on our experience with this prosthesis we advise caution when using this particular combination of implants. PMID- 26868120 TI - A simple respiratory severity score that may be used in evaluation of acute respiratory infection. AB - BACKGROUND: Acute respiratory infections are ubiquitous and may have long-term implications on respiratory health. There are many scoring systems used to objectively measure severity of respiratory infections in clinical and research settings. A respiratory severity score derived exclusively from physical exam components (RSS-HR) was studied as an objective measure of disease severity and was compared to a previously described score that uses pulse oximetry as a component of its score (RSS-SO). FINDINGS: A score was derived from 497 infants. The RSS-HR median score was higher in infants that were hospitalized (8.0) versus outpatient (4.0, p < 0.001), and those with lower respiratory tract infections (LRTI) (6.5) versus upper respiratory infections (URI) (1.0, p < 0.001). When discriminating upper versus LRTIs the concordance index of regression for RSS-HR was 0.91 and RSS-SO was 0.93. CONCLUSIONS: RSS-HR distinguishes disease severity based on level of care, as well as LRTI versus URI. PMID- 26868121 TI - Journal of Clinical Monitoring and Computing 2015 end of year summary: cardiovascular and hemodynamic monitoring. AB - Hemodynamic monitoring is essential in critically ill patients. In this regard, the Journal of Clinical Monitoring and Computing (JCMC) has become an ideal platform for publishing cardiovascular and hemodynamic monitoring-related research, as reflected by an increasing number of articles related to this topic and published in the recent years. To highlight this new progress, every New Year the journal prints a descriptive review on some important papers published last year in the JCMC and related to blood, cardiovascular function and hemodynamic monitoring. PMID- 26868122 TI - Androgen deprivation by adrenal suppression using low-dose hydrocortisone for the treatment of breast carcinoma with apocrine features: a case report illustrating this new paradigm. AB - We report on a postmenopausal patient with a secondary metastatic apocrine breast cancer successfully treated with low-dose hydrocortisone only following several lines of chemotherapy. The tumor cells in the primary and metastatic lesion exhibited a 'triple-negative' status (estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative); the androgen receptor (AR) was strongly expressed. Twenty milligrams of hydrocortisone, a low substitution dose known to suppress adrenal steroid production, twice daily led to a clinical benefit lasting for one year, with symptom control, radiologically stable disease, and steady decrease in CA15.3. Our observation demonstrates that an AR-expressing apocrine breast cancer may respond to androgen deprivation, as an ER-positive breast cancer may benefit from estrogen deprivation. It highlights the importance of further research targeting the AR pathway in apocrine carcinoma, for which androgens represent the sole (known) steroid hormone stimulating tumor growth. Future clinical trials should not only focus on AR inhibitors like enzalutamide, but also on ablative modalities like low-dose hydrocortisone aiming at medical adrenalectomy. This method of androgen deprivation is largely available, cheap, and nearly devoid of toxicity. PMID- 26868124 TI - Trends in the use of mastectomy in women with small node-negative breast cancer treated at US academic centers. AB - Breast-conserving surgery (BCS) provides equivalent survival outcomes to unilateral mastectomy. There is no survival advantage to bilateral mastectomy in average risk breast cancer. Among a cohort of breast cancer patients expected to be candidates for BCS, we examined choice of surgery and factors associated with it. A prospective cohort study of unilateral clinical Stage I breast cancer patients treated at National Comprehensive Cancer Network centers from 2000 to 2009 was performed. The proportion of patients who initially underwent mastectomy versus BCS and time to definitive surgery and chemotherapy were examined. Of 10,249 patients, 23 % underwent mastectomy as an initial surgery. No decline in the use of mastectomy as initial surgery was found. There was significant institutional variation, with rates of initial mastectomy ranging from 14 to 30 % (adjusted odds ratio: 0.42-1.38). Tumor characteristics were associated with surgical option, but with small absolute differences. Of those who received initial mastectomy, 22 % had bilateral mastectomy, with an increase over time (2000:13 % vs. 2009:30 %) and substantial institutional variation (11-34 %). Women treated with initial mastectomy had longer median times from diagnosis to complete definitive surgery (6 vs. 4 weeks) and to start of adjuvant chemotherapy (12 vs. 11 weeks). Among Stage I breast cancer, the overall use of mastectomy did not change significantly over 10 years; however, an increasing proportion of women with unilateral cancer had bilateral mastectomy, and there was wide variation in type of surgery by institution. Further studies to assess reasons for the observed wide variation are warranted. PMID- 26868126 TI - Clinical profile of megaloblastic anemia in China: a single center experience from MegA-1710 program over two decades. PMID- 26868125 TI - Establishment of a patient-derived intrahepatic cholangiocarcinoma xenograft model with KRAS mutation. AB - BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive, highly lethal tumors and lacks of effective chemo and targeted therapies. Cell lines and animal models, even partially reflecting tumor characteristics, have limits to study ICC biology and drug response. In this work, we created and characterized a novel ICC patient-derived xenograft (PDX) model of Italian origin. METHODS: Seventeen primary ICC tumors derived from Italian patients were implanted into NOD (Non Obese Diabetic)/Shi-SCID (severe combined immunodeficient) mice. To verify if the original tumor characteristics were maintained in PDX, immunohistochemical (cytokeratin 7, 17, 19, and epithelial membrane antigen) molecular (gene and microRNA expression profiling) and genetic analyses (comparative genomic hybridization array, and mutational analysis of the kinase domain of EGFR coding sequence, from exons 18 to 21, exons 2 to 4 of K-RAS, exons 2 to 4 of N-RAS, exons 9 and 20 of PI3KCA, and exon 15 of B-RAF) were performed after tumor stabilization. RESULTS: One out of 17 (5.8%) tumors successfully engrafted in mice. A high molecular and genetic concordance between primary tumor (PR) and PDX was confirmed by the evaluation of biliary epithelial markers, tissue architecture, genetic aberrations (including K-RAS G12D mutation), and transcriptomic and microRNA profiles. CONCLUSIONS: For the first time, we established a new ICC PDX model which reflects the histology and genetic characteristics of the primary tumor; this model could represent a valuable tool to understand the tumor biology and the progression of ICC as well as to develop novel therapies for ICC patients. PMID- 26868123 TI - Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor associated musculoskeletal symptoms (AIMSS). AB - The purpose of the study was to evaluate the efficacy and safety of vitamin D3 at 4000 IU/day as a treatment option for aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) when compared with the usual care dose of 600 IU D3. We conducted a single site randomized, double-blind, phase 3 clinical trial in women with AIMSS comparing change in symptoms, reproductive hormones and AI pharmacokinetics. Postmenopausal women >=18 years with stages I-IIIA breast cancer, taking AI and experiencing AIMSS [breast cancer prevention trial symptom scale-musculoskeletal (BCPT-MS) subscale >=1.5] were admitted. Following randomization, 116 patients had a run-in period of 1 month on 600 IU D3, then began the randomized assignment to either 600 IU D3 (n = 56) or 4000 IU D3 (n = 57) daily for 6 months. The primary endpoint was a change in AIMSS from baseline (after 1 month run-in) on the BCPT-MS (general MS pain, joint pain, muscle stiffness, range for each question: 0 = not at all to 4 = extremely). Groups had no statistically significant differences demographically or clinically. There were no discernable differences between the randomly allocated treatment groups at 6 months in measures of AIMSS, pharmacokinetics of anastrozole and letrozole, serum levels of reproductive hormones, or adverse events. We found no significant changes in AIMSS measures between women who took 4000 IU D3 daily compared with 600 IU D3. The 4000 IU D3 did not adversely affect reproductive hormone levels or the steady state pharmacokinetics of anastrozole or letrozole. In both groups, serum 25(OH)D remained in the recommended range for bone health (>=30 ng/mL) and safety (<50 ng/mL). PMID- 26868127 TI - Seqinspector: position-based navigation through the ChIP-seq data landscape to identify gene expression regulators. AB - BACKGROUND: The regulation of gene expression in eukaryotic cells is a complex process that involves epigenetic modifications and the interaction of DNA with multiple transcription factors. This process can be studied with unprecedented sensitivity using a combination of chromatin immunoprecipitation and next generation DNA sequencing (ChIP-seq). Available ChIP-seq data can be further utilized to interpret new gene expression profiling experiments. RESULTS: Here, we describe seqinspector, a tool that accepts any set of genomic coordinates from ChIP-seq or RNA-seq studies to identify shared transcriptional regulators. The presented web resource includes a large collection of publicly available ChIP-seq and RNA-seq experiments (>1300 tracks) performed on transcription factors, histone modifications, RNA polymerases, enhancers and insulators in humans and mice. Over-representation is calculated based on the coverage computed directly from indexed files storing ChIP-seq data (bigwig). Therefore, seqinspector is not limited to pre-computed sets of gene promoters. CONCLUSION: The tool can be used to identify common gene expression regulators for sets of co-expressed transcripts (including miRNAs, lncRNAs or any novel unannotated RNAs) or for sets of ChIP-seq peaks to identify putative protein-protein interactions or transcriptional co-factors. The tool is available at http://seqinspector.cremag.org. PMID- 26868128 TI - Behcet's disease physiopathology: a contemporary review. AB - Behcet's disease, also known as the Silk Road Disease, is a rare systemic vasculitis disorder of unknown etiology. Recurrent attacks of acute inflammation characterize Behcet's disease. Frequent oral aphthous ulcers, genital ulcers, skin lesions and ocular lesions are the most common manifestations. Inflammation is typically self-limiting in time and relapsing episodes of clinical manifestations represent a hallmark of Behcet's disease. Other less frequent yet severe manifestations that have a major prognostic impact involve the eyes, the central nervous system, the main large vessels and the gastrointestinal tract. Behcet's disease has a heterogeneous onset and is associated with significant morbidity and premature mortality. This study presents a current immunological review of the disease and provides a synopsis of clinical aspects and treatment options. PMID- 26868130 TI - Quantifying Optimal Columellar Strut Dimensions for Nasal Tip Stabilization After Rhinoplasty via Finite Element Analysis. AB - IMPORTANCE: The contribution of columellar strut grafts (CSGs) to nasal tip support has not been determined via structural mechanics. Optimal graft dimensions have yet to be objectively determined. OBJECTIVES: To use a finite element model (FEM) of the human nose to (1) determine the effect of the CSG on nasal tip support and (2) identify how suture placement contributes to tip support. DESIGN, SETTING, AND PARTICIPANTS: A multiple-component FEM of the human nose consisting of bone, skin/soft tissue, and cartilage was rendered from a computed tomographic scan. Then, CSGs of varying sizes were created, ranging from 15 * 4 * 1 mm to 25 * 8 * 1 mm, and placed in the model between the medial crura. Two FEMs were constructed for each strut size: (1) CSGs that were physically attached to the nasal spine, medial crura, and caudal septum and (2) CSGs that were not in direct contact with these structures and free to move within the soft tissue. A control model was also constructed wherein no graft was placed. MAIN OUTCOMES AND MEASURES: Nasal tip support for each model was assessed, and the resultant distribution of von Mises stress, reaction force, and strain energy density with respect to the alar cartilages were calculated. RESULTS: Compared with the control, the reaction force increased with increasing strut volume, while the strain energy density (calculated over the alar cartilages) generally decreased with increasing CSG volume. Simulations with struts that had suture attachments along the entire length of the graft generated a larger reaction force than the models without any suture attachments. Models with anteriorly placed sutures generated reaction forces similar to that of the fully sutured model, whereas the models with posterior sutures showed reaction forces similar to the fully disconnected model. CONCLUSIONS AND RELEVANCE: Insertion of CSGs does effect the amount of force the nasal tip can withstand post rhinoplasty. Moreover, anteriorly placed sutures incur reaction forces similar to struts that are fully connected to the alar cartilage. Thus, our simulations are congruent with clinical practice in that stability increases with graft size and fixation, and that sutures should be placed along either the entire CSG or the anterior most portion for optimal support. LEVEL OF EVIDENCE: NA. PMID- 26868131 TI - Early mortality in multiple myeloma: Experiences from a single institution. AB - OBJECTIVE: Multiple myeloma (MM) is a hematological malignancy that presents with infection, anemia, bone lesions, renal function impairment, and hypercalcemia. The survival of MM patients has improved in recent decades; however, early mortality remains a critical problem. The aim of this study was to identify the etiologies and clinical variables associated with early mortality in MM. In addition, the effects of bortezomib on reducing early mortality incidence were investigated. METHOD AND MATERIALS: Medical records from 122 MM patients diagnosed between November 2007 and December 2013 were retrospectively reviewed. Early mortality was defined as death by any cause within the first 180 days after pathological diagnosis. RESULTS: In newly diagnosed MM patients, early mortality occurred in 22.95% of patients. Infection accounted for 67.86% of early deaths. Multivariate analyses by Cox proportional-hazards regression showed that higher beta2-microglobulin (P < 0.001) and serum lactate dehydrogenase (P < 0.001) levels, and lower serum albumin levels (P < 0.001) were associated with early mortality. Both first-line and greater than or equal to second-line bortezomib treatments were not associated with superior 180-day overall survival (P = 0.546 for first-line bortezomib treatment; P = 0.066 for greater than or equal to second-line bortezomib treatment). CONCLUSION: Our results suggest that infection is the leading cause of early death in MM. High beta2-microglobulin, high serum lactate dehydrogenase, and low serum albumin levels are poor prognostic factors for early mortality. Bortezomib therapy does not appear to reduce the incidence of early mortality in MM patients. PMID- 26868129 TI - Red Sea Atlantis II brine pool nitrilase with unique thermostability profile and heavy metal tolerance. AB - BACKGROUND: Nitrilases, which hydrolyze nitriles in a one-step reaction into carboxylic acids and ammonia, gained increasing attention because of the abundance of nitrile compounds in nature and their use in fine chemicals and pharmaceutics. Extreme environments are potential habitats for the isolation and characterization of extremozymes including nitrilases with unique resistant properties. The Red Sea brine pools are characterized by multitude of extreme conditions. The Lower Convective Layer (LCL) of the Atlantis II Deep Brine Pool in the Red Sea is characterized by elevated temperature (68 degrees C), high salt concentrations (250 0/00), anoxic conditions and high heavy metal concentrations. RESULTS: We identified and isolated a nitrilase from the Atlantis II Deep Brine Pool in the Red Sea LCL. The isolated 338 amino-acid nitrilase (NitraS-ATII) is part of a highly conserved operon in different bacterial phyla with indiscernible function. The enzyme was cloned, expressed and purified. Characterization of the purified NitraS-ATII revealed its selectivity towards dinitriles, which suggests a possible industrial application in the synthesis of cyanocarboxylic acids. Moreover, NitraS-ATII showed higher thermal stability compared to a closely related nitrilase, in addition to its observed tolerance towards high concentrations of selected heavy metals. CONCLUSION: This enzyme sheds light on evolution of microbes in the Atlantis II Deep LCL to adapt to the diverse extreme environment and can prove to be valuable in bioremediation processes. PMID- 26868132 TI - Association of RBP4 levels with increased arterial stiffness in adolescents with family history of type 2 diabetes. AB - BACKGROUND: The aim of this study was to explore the impact of family history of type 2 diabetes (FH2D) on arterial stiffness in young people and its relationship to adipocytokines. METHODS: This case-control study included 52 adolescents (male/female 28/24) with FH2D (FH2D+) and 40 adolescents (male/female 21/19) without FH2D (FH2D-). Anthropometric measurements, including height, weight, waist circumference (WC), and blood pressure, were obtained. Blood samples were collected, fasting plasma glucose (FPG), serum lipids, Retinol Binding Protein 4 (RBP4), C reactive protein (CRP), adiponectin and visfatin were examined. Brachial-ankle pulse wave velocity (baPWV) was used to evaluate arterial stiffness. Visceral fat area (VFA) was measured by computerized tomography. RESULTS: Compared with FH2D- group, FH2D+ group had a significantly higher oral glucose tolerance test (OGTT) 2-hour insulin, RBP4 and baPWV levels, a lower adiponectin and glucose infusing rate (GIR) (P<0.05). BaPWV was positively correlated with age, systolic blood pressure (SBP), diastolic blood pressure (DBP), 2-hour (OGTT) insulin, RBP4, and VFA, and negatively correlated with GIR in FH2D+ group. After multivariate analysis, age, SBP, RBP4 and VFA maintained an independent association with baPWV in FH2D+ group (P<0.05), while only age, SBP, and VFA were independent predictors of baPWV in FH2D- group (P<0.05). CONCLUSIONS: These findings led to the conclusion that RBP4 level was associated with increased arterial stiffness in young subjects with family history of type 2 diabetes. PMID- 26868133 TI - SOX6 gene polymorphism (rs16933090) and markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus. AB - BACKGROUND: The present study was designed to investigate the association between the polymorphism of the SOX6 gene (rs16933090) and subclinical markers of carotid atherosclerosis, such as carotid intima media thickness (CIMT), the number of affected segments of carotid arteries and the sum of plaque thickness in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between the rs16933090 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. METHODS: A total of 595 T2DM subjects were enrolled in the cross-sectional study. Markers of carotid atherosclerosis were assessed by ultrasonography. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of SOX6 gene (rs16933090) was performed using KASPar assays. RESULTS: In our study we demonstrated the effect of the rs16933090 on coronary calcium score obtained at CCTA, whereas we did not demonstrate any association between the tested polymorphism (rs16933090) and the presence of more than 50% stenotic lesions in coronary arteries, the sum of plaque thickness, the number of involved carotid segments, high-sensitivity C reactive protein, the presence of carotid plaques, and the presence of unstable carotid plaques. CONCLUSIONS: In our study, we demonstrated the effect of the rs16933090 on coronary calcium score obtained at CCTA, whereas we did not demonstrate an important effect of the rs16933090 on either subclinical markers of carotid atherosclerosis or the presence of more than 50% stenotic lesions in coronary arteries in Caucasians with T2DM. We presume that the rs16933090 plays a minor role in the development of subclinical atherosclerosis in subjects with T2DM. PMID- 26868134 TI - Misdiagnosis of plexiform neurofibroma as venous malformation in pediatric patients. AB - BACKGROUND: The aim of this study was to identify Magnetic Resonance Imaging (MRI) characteristics that reliably distinguish deep plexiform neurofibromas (PNFs) from venous malformations (VMs). METHODS: A database search was conducted for patients that were referred with a vascular anomaly but had a neurofibroma instead. Clinical and imaging features of patients with venous malformations as the most common referral diagnosis were compared to those with PNFs. The imaging features of deep PNFs recorded were: anatomical location, size, morphology, margins, signal intensity and post-contrast enhancement pattern. RESULTS: Ten patients with PNFs were identified. Five patients had adequate imaging. These five patients were included in our study. There were 3 female and 2 male patients ranging in age from 10 months to 21 years. Deep PNFs were located in the cervicofacial region (N.=3), lower extremity (N.=1) and back/flank region (N.=1). The most common clinical features of all these patients were palpable mass (N.=5) and pain (N.=4). The MRI features that distinguished VMs from deep PNFs were the serpiginous morphology, relatively intermediate T-2 signal intensity and peculiar enhancement pattern without fluid-fluid levels or phleboliths and nerve root involvement. The target sign can be regularly found in PNFs, but may be also present in VMs and other vascular lesions. CONCLUSIONS: Target signs, a typical sign of PNFs may be absent and can also be found in vascular anomalies, leading to confusion in diagnosis. PNFs can be reliably distinguished from VMs on MRI based on the above mentioned features. PMID- 26868135 TI - Sulodexide reduces the inflammatory reaction and senescence of endothelial cells in conditions involving chronic venous disease. AB - BACKGROUND: According to previous studies, sulodexide suppresses intravascular inflammation when used in patients with chronic venous disease (CVD). In the current study, we tested the effect of prolonged in vitro exposure of human venous endothelial cells to the serum from patients with CVD, examining the function of these cells and how it is modified when these cells are simultaneously exposed to sulodexide. METHODS: Human umbilical venous cells (HUVEC) were cultured in standard medium (control), in medium supplemented with 5% serum pooled from CVD patients (CVD-serum) or in medium from CVD patients who were treated with sulodexide (CVD-serum-SUL). The synthesis of interleukin-6 (IL 6), monocyte chemoattractant protein -1(MCP-1) and soluble intercellular adhesion molecule - 1 (s-ICAM-1) were studied at the beginning of incubation and were measured after 9 and 15 days of exposure to the studied media. The concentration of IL-6 after cell stimulation by interleukin -1 (IL-1) was also measured. In a subsequent part of the experiment, the effect of the studied sera on the in vitro replicative ageing of HUVEC was evaluated. A total of 15 passages of the cell culture were performed and both the PDT (population doubling time) and the cell hypertrophy were assessed. RESULTS: The concentrations of Il-6, MCP-1, and ICAM-1 gradually increased in the supernatants containing 5% CVD serum compared with the control medium. In the supernatants obtained after cell incubation with serum from sulodexide treated patients, the increase in concentrations of IL-6, MCP-1 and ICAM-1 was significantly less than the control. Release of IL-6 after stimulation with IL-1 (100 pg/mL) was the highest in the CVD-serum group: 3540+/ 670 pg/105 cells vs. 1850+/-540 pg/105 cells in the control (P<0.01 vs. CVD serum) and 2320 +/-430 pg/105 cells in CVD-serum-SUL (P<0.02 vs. CVD-serum). PDT was significantly longer in the cells incubated with CVD serum compared with the control group, and PDT was reduced when serum from sulodexide treated patients was used. The cells became senescent in the presence of CVD serum, but the cells obtained from patients at the end of 8 weeks of treatment with sulodexide showed a much weaker inflammatory phenotype than the CVD group. CONCLUSIONS: Chronic in vitro exposure of HUVEC to medium supplemented with CVD patient serum induces an inflammatory phenotype. Sulodexide treatment significantly reduces that effect and slows HUVEC senescence in the milieu of CVD serum. PMID- 26868136 TI - Intravenous Colistin in the treatment of multidrug-resistant Acinetobacter in neonates. AB - BACKGROUND: Neonatal sepsis caused by multidrug-resistant gram-negative bacteria has been reported in different parts of the world. It is a major threat to neonatal care, carrying a high rate of morbidity and mortality. While Colistin is the treatment of choice, few studies have reported its use in neonatal patients. METHODS: A retrospective descriptive study of all neonatal patients who had multidrug-resistant Acinetobacter sepsis and were treated with Colistin over a 2 year period. Patients' charts and hospital laboratory data were reviewed. RESULTS: During the study period, 21 newborns were treated with Colistin. All had sepsis evident by positive blood culture and clinical signs of sepsis. The median gestational age and birth weight were 33 weeks (26-39) and 1700 g (700-3600), respectively. Nine (43 %) were very low birth weight infants. Eighteen (86 %) were preterm infants. Nineteen (91 %) newborns survived. No renal impairment is documented in any of our patients. Fourteen (67 %) of our patients had elevated eosinophil counts following Colistin treatment, for those patients, the average eosinophilic counts +/- standard deviation before and after Colistin therapy were 149.08 +/- 190.38 to 1193 +/- 523.29, respectively, with a p value of less than 0.0001. CONCLUSION: Our study showed that Colistin was both effective and safe for treating multidrug-resistant Acinetobacter neonatal sepsis. This is a retrospective study. No universal protocol was used for the patients. The factors that might affect the response or cause side effects are difficult to evaluate. PMID- 26868138 TI - Cesium adsorption/desorption behavior of clay minerals considering actual contamination conditions in Fukushima. AB - Cesium adsorption/desorption experiments for various clay minerals, considering actual contamination conditions in Fukushima, were conducted using the (137)Cs radioisotope and an autoradiography using imaging plates (IPs). A 50 MUl solution containing 0.185 ~ 1.85 Bq of (137)Cs (10(-11) ~ 10(-9 )molL(-1) of (137)Cs) was dropped onto a substrate where various mineral particles were arranged. It was found that partially-vermiculitized biotite, which is termed "weathered biotite" (WB) in this study, from Fukushima sorbed (137)Cs far more than the other clay minerals (fresh biotite, illite, smectite, kaolinite, halloysite, allophane, imogolite) on the same substrate. When WB was absent on the substrate, the amount of (137)Cs sorbed to the other clay minerals was considerably increased, implying that selective sorption to WB caused depletion of radiocesium in the solution and less sorption to the coexisting minerals. Cs-sorption to WB continued for about one day, whereas that to ferruginous smectite was completed within one hour. The sorbed (137)Cs in WB was hardly leached with hydrochloric acid at pH 1, particularly in samples with a longer sorption time. The presence/absence of WB sorbing radiocesium is a key factor affecting the dynamics and fate of radiocesium in Fukushima. PMID- 26868137 TI - Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and meta-analysis of randomized trials. AB - OBJECTIVE: To evaluate the outcomes with use of renin angiotensin system (RAS) blockers compared with other antihypertensive agents in people with diabetes. DESIGN: Meta-analysis. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and the Cochrane central register of controlled trials databases for randomized trials of RAS blockers versus other antihypertensive agents in people with diabetes mellitus. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, and end stage renal disease. RESULTS: The search yielded 19 randomized controlled trials that enrolled 25,414 participants with diabetes for a total of 95,910 patient years of follow-up. When compared with other antihypertensive agents, RAS blockers were associated with a similar risk of death (relative risk 0.99, 95% confidence interval 0.93 to 1.05), cardiovascular death (1.02, 0.83 to 1.24), myocardial infarction (0.87, 0.64 to 1.18), angina pectoris (0.80, 0.58 to 1.11), stroke (1.04, 0.92 to 1.17), heart failure (0.90, 0.76 to 1.07), and revascularization (0.97, 0.77 to 1.22). There was also no difference in the hard renal outcome of end stage renal disease (0.99, 0.78 to 1.28) (power of 94% to show a 23% reduction in end stage renal disease). CONCLUSIONS: In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and beta blockers at reducing the risk of hard cardiovascular and renal endpoints. These findings support the recommendations of the guidelines of the European Society of Cardiology/European Society of Hypertension and eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to also use other antihypertensive agents in people with diabetes but without kidney disease. PMID- 26868139 TI - Differentiating the grades of thymic epithelial tumor malignancy using textural features of intratumoral heterogeneity via (18)F-FDG PET/CT. AB - OBJECTIVE: We aimed to explore the ability of textural heterogeneity indices determined by (18)F-FDG PET/CT for grading the malignancy of thymic epithelial tumors (TETs). METHODS: We retrospectively enrolled 47 patients with pathologically proven TETs who underwent pre-treatment (18)F-FDG PET/CT. TETs were classified by pathological results into three subgroups with increasing grades of malignancy: low-risk thymoma (LRT; WHO classification A, AB and B1), high-risk thymoma (B2 and B3), and thymic carcinoma (TC). Using (18)F-FDG PET/CT, we obtained conventional imaging indices including SUVmax and 20 intratumoral heterogeneity indices: i.e., four local-scale indices derived from the neighborhood gray-tone difference matrix (NGTDM), eight regional-scale indices from the gray-level run-length matrix (GLRLM), and eight regional-scale indices from the gray-level size zone matrix (GLSZM). Area under the receiver operating characteristic curve (AUC) was used to demonstrate the abilities of the imaging indices for differentiating subgroups. Multivariable logistic regression analysis was performed to show the independent significance of the textural indices. Combined criteria using optimal cutoff values of the SUVmax and a best-performing heterogeneity index were applied to investigate whether they improved differentiation between the subgroups. RESULTS: Most of the GLRLM and GLSZM indices and the SUVmax showed good or fair discrimination (AUC >0.7) with best performance for some of the GLRLM indices and the SUVmax, whereas the NGTDM indices showed relatively inferior performance. The discriminative ability of some of the GLSZM indices was independent from that of SUVmax in multivariate analysis. Combined use of the SUVmax and a GLSZM index improved positive predictive values for LRT and TC. CONCLUSIONS: Texture analysis of (18)F-FDG PET/CT scans has the potential to differentiate between TET tumor grades; regional-scale indices from GLRLM and GLSZM perform better than local-scale indices from the NGTDM. The SUVmax and heterogeneity indices may have complementary value in differentiating TET subgroups. PMID- 26868140 TI - Realization of ppm-level CO detection with exceptionally high sensitivity using reduced graphene oxide-loaded SnO2 nanofibers with simultaneous Au functionalization. AB - We have realized the highly sensitive, selective ppm-level carbon monoxide (CO) detection based on graphene oxide (RGO) nanosheets-loaded SnO2 nanofibers with simultaneous Au functionalization. The interplay between RGO/Au and SnO2 in terms of transfer of charge carriers and modulation of potential barriers is responsible for the exceptionally high CO detectability. PMID- 26868141 TI - Critical role of CCL22/CCR4 axis in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8alpha(+) CD103(+) dendritic cells. AB - Macrophages and dendritic cells (DCs) in murine spleen are essential for the maintenance of immune homeostasis by elimination of blood-borne foreign particles and organisms. It has been reported that splenic DCs, especially CD8alpha(+) CD103(+) DCs, are responsible for tolerance to apoptosis-associated antigens. However, the molecular mechanism by which these DCs maintain immune homeostasis by blood-borne apoptotic cell clearance remains elusive. Here, we found that the CCL22/CCR4 axis played a critical role in the maintenance of immune homeostasis during apoptotic cell clearance by splenic CD8alpha(+) CD103(+) DCs. The present results revealed that systemic administration of apoptotic cells rapidly induced a large number of CCL22 and CCR4(+) regulatory T (Treg) cells in the spleen of C57BL/6J mice. Further study demonstrated that CD8alpha(+) CD103(+) DCs dominantly produce much higher CCL22 than CD8alpha(+) CD103(-) DCs. Moreover, the transient deletion of CD8alpha(+) CD103(+) DCs caused a decrease in CCL22 levels together with CCR4(+) Treg cell percentage. Subsequently, the levels of some pro inflammatory cytokines, such as interleukin-17 and interferon-gamma in the spleen with the absence of CD8alpha(+) CD103(+) DCs increased in response to the administration of apoptotic cells. Hence, intravenous injection of apoptotic cells induced a subsequent increase in CCL22 expression and CCR4(+) Treg cells, which contribute to the maintenance of immune homeostasis at least partially by splenic CD8alpha(+) CD103(+) DCs. PMID- 26868142 TI - Peptide mini-scaffold facilitates JNK3 activation in cells. AB - Three-kinase mitogen-activated protein kinase (MAPK) signaling cascades are present in virtually all eukaryotic cells. MAPK cascades are organized by scaffold proteins, which assemble cognate kinases into productive signaling complexes. Arrestin-3 facilitates JNK activation in cells, and a short 25-residue arrestin-3 peptide was identified as the critical JNK3-binding element. Here we demonstrate that this peptide also binds MKK4, MKK7, and ASK1, which are upstream JNK3-activating kinases. This peptide is sufficient to enhance JNK3 activity in cells. A homologous arrestin-2 peptide, which differs only in four positions, binds MKK4, but not MKK7 or JNK3, and is ineffective in cells at enhancing activation of JNK3. The arrestin-3 peptide is the smallest MAPK scaffold known. This peptide or its mimics can regulate MAPKs, affecting cellular decisions to live or die. PMID- 26868143 TI - CD27-positive hairy cell leukemia-Japanese variant. AB - We report a very rare case of a 45-year-old Japanese male patient with hairy cell leukemia-Japanese variant (HCL-JV) expressing CD27. The patient showed a high number of abnormal peripheral lymphocytes, thrombocytopenia, and severe splenomegaly but no lymphadenopathy. Histology of the resected spleen showed small-sized lymphoma cells diffusely infiltrating the red pulp without follicle formation. By immunohistochemistry, lymphoma cells were negative for CD3, CD5, CD8, CD10, CD34, cyclin-D1, and annexin A1 but positive for CD20 and BCL2. BRAF V600E mutation was not observed. Bone marrow aspirate showed preserved normal hematopoietic cells with invasion of lymphoma cells in an interstitial pattern without obvious nodules. The cells had abundant pale cytoplasm and round nuclei with inconspicuous nucleoli. After natural drying, the cells had unevenly distributed microvilli. Flow cytometric analysis demonstrated positivity for CD11a, CD11c, CD19, CD20, CD22, CD27, surface IgG, and lambda but not for CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD21, CD23, CD25, CD30, CD34, CD38, CD43, CD56, CD57, CD103, IgD, IgM, and kappa. Monoclonal expansion of B cells was confirmed by an immunoglobulin heavy chain (IgH) rearrangement band as demonstrated by Southern blot hybridization. The lymphoma cells had unevenly distributed long, large, and broad-based microvilli, which resembled splenic diffuse red pulp small B cell lymphoma (SDRPL) cells. CD27 expression is extremely rare in HCL-JV, but the young age of the patient and high peripheral WBC counts were similar to HCL JV, which suggests, in this case, an intermediate disease between SDRPL and HCL JV. PMID- 26868144 TI - Funisitis is associated with adverse neonatal outcome in low-risk unselected deliveries at or near term. AB - This study aimed to determine the incidence and clinical outcomes for varying patterns of placental histological inflammation (consistent with fetal or maternal inflammatory response) in an unselected population of >1000 women with a singleton pregnancy resulting in live birth delivering at or near term. One thousand one hundred nineteen cases were studied in a blind, prospective, unselected study with placentas categorized into five histological subgroups reflecting underlying maternal or fetal inflammatory response. Clinical outcomes studied included interventional delivery, an Apgar score <7 at 1 min, neonatal acidosis (pH < 7.2) and admission to neonatal special care. One hundred eighty eight placentas (17%) showed histological evidence of acute inflammation: 64 with funisitis (with or without other inflammation; 6%); 16 with extensive acute inflammation across the chorionic plate, free membranes and subchorionic fibrin (1%); 28 with acute inflammation restricted to the chorionic plate (2%); 12 with acute inflammation restricted to the free membranes (1%) and 68 with acute inflammation restricted to the subchorionic fibrin (6%). Features of extensive acute inflammation were significantly associated with increased rate of interventional delivery (assisted vaginal delivery or emergency caesarean section; P < 0.01). The presence of funisitis was significantly associated with interventional delivery and other adverse outcomes including an Apgar score <7 at 1 min, clinical evidence of sepsis and admission to the neonatal intensive care unit (P < 0.05 for all). The data represent a quantitative rather than purely qualitative analysis of the contribution of histological lesions related to inflammation on short-term adverse neonatal outcomes and interventional delivery. Funisitis and extensive inflammation are associated with adverse clinical outcomes, but the precise mechanism underlying these remains to be elucidated. PMID- 26868145 TI - Uniportal thoracoscopic lobectomy for intralobar pulmonary sequestration. AB - BACKGROUND: Pulmonary sequestration is an uncommon congenital condition for which surgical resection is usually indicated - either via open thoracotomy or conventional multi-port Video-Assisted Thoracoscopic Surgery (VATS). Of the two types of sequestration, intralobar sequestration is technically more challenging to resect. CASE PRESENTATION: We report the management of a 34 year old male patient with a long history of respiratory symptoms, and an extensively diseased right lower lobe. A diagnosis of sequestration was confirmed by CT scanning, showing three separate anomalous feeding vessels arising from the abdominal aorta. A right lower lobectomy using a Uniportal VATS approach was performed, and the patient discharged home on the fourth post-operative day. CONCLUSION: This is the first report to our knowledge demonstrating the safety and feasibility of the Uniportal approach for the resection of a relatively challenging intralobar sequestration. PMID- 26868147 TI - Hemoglobin level is a more predictive diagnostic marker for acute pyelonephritis than mean platelet volume. PMID- 26868146 TI - Associations of pulmonary function with serum biomarkers and dialysis adequacy in patients undergoing peritoneal dialysis. AB - BACKGROUND: As lung impairment is an indicator of increased morbidity and mortality in patients receiving continuous ambulatory peritoneal dialysis (CAPD), the risk factors associated with impaired lung function are of great significance. The aim of this study is to elucidate the effects of inflammatory biomarkers and dialysis adequacy on pulmonary function, in CAPD patients. METHODS: 101 patients undergoing CAPD, 30 CKD5 patients and 30 healthy subjects were enrolled. Spirometry and serum biomarkers were evaluated in each subject. Pulmonary function was compared among patients and control groups. Pearson analysis was used to analyze the correlation between serum biomarkers, dialysis adequacy and pulmonary function. RESULTS: Lower vital capacity, maximal voluntary ventilation (MVV), forced vital capacity (FVC), peak expiratory flow (PEF), maximal mid-expiratory flow rate (MMEF), and diffusing capacity of the lung for carbon monoxide (DLCO) were observed in the CAPD group (all P < 0.05) when compared with control subjects. DLCO % was negatively correlated with CRP (r = 0.349, P = 0.007) and positively correlated with albumin (r = 0.401, P = 0.002). Total Kt/V was associated positively with MMEF % (r = 0.316, P = 0.019), and MVV % (r = 0.362, P = 0.007). nPNA was positively correlated with FVC % (r = 0.295, P = 0.049) and MMEF % (r = 0.381, P = 0.010). CONCLUSION: The results suggest that lung function decline was directly related to higher CRP level, hypoalbuminemia, and dialysis inadequacy. These findings provide the evidence that inflammation and dialysis adequacy play a role in predicting outcomes of CAPD patients with pulmonary impairment. PMID- 26868148 TI - SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence. AB - Recent evidence has revealed that senescence induction requires fine-tuned activation of p53, however, mechanisms underlying the regulation of p53 activity during senescence have not as yet been clearly established. We demonstrate here that SCF(Fbxo22)-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCF(Fbxo22) ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. Ectopic expression of a catalytic mutant of KDM4A stabilizes p53 and enhances p53 interaction with PHF20 in the presence of Fbxo22. SCF(Fbxo22)-KDM4A is required for the induction of p16 and senescence-associated secretory phenotypes during the late phase of senescence. Fbxo22(-/-) mice are almost half the size of Fbxo22(+/-) mice owing to the accumulation of p53. These results indicate that SCF(Fbxo22)-KDM4A is an E3 ubiquitin ligase that targets methylated p53 and regulates key senescent processes. PMID- 26868149 TI - Comparison of alkali treatments for efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith. AB - Two separate temperature and time ranges were respectively conducted for optimizing release of p-coumaric acid and enzymatic saccharification of sorghum pith by NaOH pretreatment using response surface methodology. Two desirable pretreatment conditions were selected as follows: 37 degrees C, 2% NaOH and 12h, and 100 degrees C, 1.75% NaOH and 37min in the low and high temperature ranges, respectively. Under these conditions, the enzymatic glucose yields were 85.6% and 90.4% respectively, whereas p-coumaric acid yields were 95.1% and 98.1% respectively. The final recovery of esterified p-coumaric acid reached 82.8% and 87.4% respectively after further separation with HP-20 resin. Interestingly, strong linear correlations exist between p-coumaric acid release with glucan saccharification yield and lignin dissolution. These results indicate that sorghum pith could be an attractive source for natural p-coumaric acid and efficient release of p-coumaric acid and enzymatic saccharification of sorghum pith can be achieved by mild NaOH pretreatment. PMID- 26868150 TI - The shift of the microbial community in activated sludge with calcium treatment and its implication to sludge settleability. AB - The sludge settleability is of prime importance for the activated sludge process. The effect of calcium ion on the biological performance of sludge was investigated in a lab-scale activated sludge system with varying Ca(2+) concentration. Results indicated that addition of 150mg/L Ca(2+) to the influent significantly improved the settling characteristics and metabolic reactivity of activated sludge in the bioreactors. Analyses using denaturing gradient gel electrophoresis (DGGE) and 16S rRNA sequencing showed that a significant difference in the presence of certain bacterial groups between the sludge systems with 150mg/L Ca(2+) and those with 0-100mg/L Ca(2+) addition. Ca(2+) also increased the production of the extracellular polymeric substance (EPS) and facilitated the development of microbial cluster in the bioreactor. Study showed that an addition of 150mg/L Ca(2+) to the influent provides a simple approach to improve the settling properties of activated sludge and maintain high pollutant removal efficiency. PMID- 26868151 TI - Microalgal growth in municipal wastewater treated in an anaerobic moving bed biofilm reactor. AB - Nutrient removal from the effluent of an anaerobic moving bed biofilm reactor (AnMBBR) treated with microalgae was evaluated. Algal treatment was highly efficient in removal of nutrients and discharge limits were met after 3days. Extending the cultivation time from 3 to 5days resulted in a large increase in biomass, from 233.3+/-49.3 to 530.0+/-72.1mgL(-1), despite nutrients in the water being exhausted after 3days (ammonium 0.04mgL(-1), orthophosphate <0.05mgL(-1)). Biomass productivity, lipid content and quality did not differ in microalgal biomass produced in wastewater sampled before the AnMBBR. The longer cultivation time resulted in a slight increase in total lipid concentration and a significant decrease in linolenic acid concentration in all treatments. Differences were observed in chemical oxygen demand, which decreased after algal treatment in wastewater sampled before the AnMBBR whereas it increased after algal treatment in the effluent from the AnMBBR. PMID- 26868152 TI - Simultaneous inhibition of sulfate-reducing bacteria, removal of H2S and production of rhamnolipid by recombinant Pseudomonas stutzeri Rhl: Applications for microbial enhanced oil recovery. AB - Sulfate-reducing bacteria (SRB) are widely existed in oil production system, and its H2S product inhibits rhamnolipid producing bacteria. In-situ production of rhamnolipid is promising for microbial enhanced oil recovery. Inhibition of SRB, removal of H2S and production of rhamnolipid by recombinant Pseudomonas stutzeri Rhl were investigated. Strain Rhl can simultaneously remove S(2-) (>92%) and produce rhamnolipid (>136mg/l) under S(2-) stress below 33.3mg/l. Rhl reduced the SRB numbers from 10(9) to 10(5)cells/ml, and the production of H2S was delayed and decreased to below 2mg/l. Rhl also produced rhamnolipid and removed S(2-) under laboratory simulated oil reservoir conditions. High-throughput sequencing data demonstrated that addition of strain Rhl significantly changed the original microbial communities of oilfield production water and decreased the species and abundance of SRB. Bioaugmentation of strain Rhl in oilfield is promising for simultaneous control of SRB, removal of S(2-) and enhance oil recovery. PMID- 26868153 TI - Enhancement of microalgae production by embedding hollow light guides to a flat plate photobioreactor. AB - To offset the adverse effects of light attenuation on microalgae growth, hollow polymethyl methacrylate (PMMA) tubes were embedded into a flat-plate photobioreactor (PBR) as light guides. In this way, a fraction of incident light could be transmitted and emitted to the interior of the PBR, providing a secondary light source for cells in light-deficient regions. The average light intensity of interior regions 3-6cm from surfaces with 70MUmolm(-2)s(-1) incident light was enhanced 2-6.5 times after 3.5days cultivation, resulting in a 23.42% increase in biomass production to that cultivated in PBR without PMMA tubes. The photosynthetic efficiency of microalgae in the proposed PBR was increased to 12.52%. Moreover, the installation of hollow PMMA tubes induced turbulent flow in the microalgae suspension, promoting microalgae suspension mixing. However, the enhanced biomass production was mainly attributed to the optimized light distribution in the PBR. PMID- 26868154 TI - Immobilization of metal-humic acid complexes in anaerobic granular sludge for their application as solid-phase redox mediators in the biotransformation of iopromide in UASB reactors. AB - Metal-humic acid complexes were synthesized and immobilized by a granulation process in anaerobic sludge for their application as solid-phase redox mediators (RM) in the biotransformation of iopromide. Characterization of Ca- and Fe-humic acid complexes revealed electron accepting capacities of 0.472 and 0.556milli equivalentsg(-1), respectively. Once immobilized, metal-humic acid complexes significantly increased the biotransformation of iopromide in upflow anaerobic sludge blanket (UASB) reactors. Control UASB reactor (without humic material) achieved 31.6% of iopromide removal, while 80% was removed in UASB reactors supplied with each metal-humic acid complex. Further analyses indicated multiple transformation reactions taking place in iopromide including deiodination, N dealkylation, decarboxylation and deacetylation. This is the first successful application of immobilized RM, which does not require a supporting material to maintain the solid-phase RM in long term operation of bioreactors. The proposed redox catalyst could be suitable for enhancing the redox conversion of different recalcitrant pollutants present in industrial effluents. PMID- 26868155 TI - Evaluation of productivity and antioxidant profile of solid-state cultivated macrofungi Pleurotus albidus and Pycnoporus sanguineus. AB - The aim of this study was to investigate the production profile of Pleurotus albidus and Pycnoporus sanguineus on different waste substrates containing natural phenolics, and also to investigate whether phenolic-rich substrates can improve the phenolic content of these macrofungi. The medium formulated with Pinus sp. sawdust (PSW) made possible the highest yields (2.62+/-0.73%) of P. sanguineus. However, the supplementation of PSW with apple waste (AW) resulted in better P. albidus yields (23.94+/-2.92%). The results indicated that the substrate composition affected macrofungi production, also the chemical composition and the presence of phenolic compounds in the production media influence phenolic content and antioxidant activity in macrofungi. PMID- 26868156 TI - Enhancing ethanol production from thermophilic and mesophilic solid digestate using ozone combined with aqueous ammonia pretreatment. AB - Pretreatment with ozone combined with aqueous ammonia was used to recover residual organic carbon from recalcitrant solid digestate for ethanol production after anaerobic digestion (AD) of rice straw. Methane yield of AD at mesophilic and thermophilic conditions, and ethanol production of solid digestate were investigated. The results showed that the methane yield at thermophilic temperature was 72.2% higher than that at mesophilic temperature under the same conditions of 24days and 17% solid concentration. And also the ethanol production efficiency of solid digestate after thermophilic process was 24.3% higher than that of solid digestate after mesophilic process. In this study, the optimal conditions for integrated methane and ethanol processes were determined as 55 degrees C, 17% solid concentration and 24days. 58.6% of glucose conversion, 142.8g/kg of methane yield and 65.2g/kg of ethanol yield were achieved, and the highest net energy balance was calculated as 6416kJ/kg. PMID- 26868157 TI - Cultivation of Scenedesmus obliquus in liquid hydrolysate from flash hydrolysis for nutrient recycling. AB - The production of biofuels from microalgae is associated with high demands of nutrients (nitrogen and phosphorus) required for growth. Recycling nutrients from the residual biomass is essential to obtain a sustainable production. In this work, the aqueous phase obtained from flash hydrolysis of Scenedesmus sp. was used as cultivation medium for a microalga of the same genus, to assess the feasibility of this technique for nutrient recycling purposes. Batch and continuous cultivations were carried out, to determine growth performances in this substrate compared to standard media, and verify if a stable biomass production could be obtained. In continuous experiments, the effect of hydrolysate inlet concentration and of residence time were assessed to optimize nutrient supply in relation to productivity. Results obtained show that nutrient recycling is feasible by treating biomass with flash hydrolysis, and Scenedesmus is capable of recycling large amounts of recovered nutrients. PMID- 26868158 TI - Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta analysis. AB - The advent of antiretroviral therapy has significantly improved AIDS-related morbidity and mortality. Yet, among people living with HIV, deaths due to non AIDS-defining illnesses have been on the rise. The objective of this study was to provide information about the global prevalence and distribution of non-AIDS causes of death in the last ten years among people living with HIV receiving antiretroviral therapy, by income levels of countries. We used broad search terms in Google Scholar, PubMed, and EMBASE to identify all studies that investigated the cause of death among people living with HIV receiving antiretroviral therapy, published after January 1, 2005. References were also identified from review articles and reference lists. Inclusion criteria were English language, the study's end date was after 2005, all patients were HIV-positive, at least two thirds of the patients were receiving antiretroviral therapy, at least one patient died of non-AIDS causes of death. Titles, abstracts, and articles were reviewed by at least two independent readers. Of 2951 titles identified in our original search, 151 articles were selected for further screening. We identified 19 studies meeting our full criteria, with patients from 55 different nations. Pooled non-AIDS causes of death prevalence estimates in high-income countries were 53.0% (95% confidence interval, 43.6-62.3), in developing countries 34.0% (95% confidence interval, 20.3-49.1), and in sub-Saharan countries 18.5% (95% confidence interval, 13.8-23.7). Statistically significant variation was noted within and between categories. Our findings show that a significant number of people living with HIV across the world die from cardiovascular disease, non-AIDS malignancies, and liver disease. There is a global need for further scrutiny in all regions to improve preventive measures and early detection according to distinct causes of death patterns. PMID- 26868159 TI - Cryptococcemia in primary HIV infection. AB - Opportunistic infections have been reported infrequently in primary HIV infection. We report a case of cryptococcemia in primary HIV infection. To our knowledge there has not been such a case reported. Our case highlights the need for clinicians to be wary of other opportunistic infections, including cryptococcosis, in primary HIV infection. PMID- 26868160 TI - Speckle-tracking imaging in patients with Eisenmenger syndrome. AB - BACKGROUND: Adults with Eisenmenger syndrome have a survival advantage over those with idiopathic pulmonary arterial hypertension. Improved survival may result from preservation of right ventricular (RV) function. AIMS: To assess left ventricular (LV) and RV remodelling in patients with Eisenmenger syndrome compared to a control population, using speckle-tracking imaging. METHODS: Adults with Eisenmenger syndrome and healthy controls were enrolled into this prospective two-centre study. Patients with Eisenmenger syndrome with low acoustic windows, irregular heart rhythm or complex congenital heart disease were excluded. Clinical assessment, B-type natriuretic peptide (BNP), 6-minute walk test and echocardiography (including dedicated views to perform offline two dimensional-speckle-tracking analysis) were performed on inclusion. RESULTS: Our patient population (n=37; mean age 42.3 +/- 17 years) was mostly composed of patients with ventricular septal defect (37.8%) or atrial septal defect (35.1%). Compared with the control population (n=30), patients with Eisenmenger syndrome had reduced global LV longitudinal strain (-17.4 +/- 3.5 vs. -22.4 +/- 2.3; P<0.001), RV free-wall longitudinal strain (-15.0 +/- 4.7 vs. -29.9 +/- 6.8; P<0.001) and RV transverse strain (25.8 +/- 25.0 vs. 44.5 +/- 15.1; P<0.001). Patients with Eisenmenger syndrome also more frequently presented a predominant apical longitudinal and transverse strain profile. Among patients with Eisenmenger syndrome, those with a post-tricuspid shunt presented with reduced global LV longitudinal strain but increased RV transverse strain, compared to patients with pre-tricuspid shunt. CONCLUSION: Patients with Eisenmenger syndrome had impaired longitudinal RV and LV strain, but present a relatively important apical deformation. RV and LV remodelling, as assessed by speckle-tracking imaging, differ between patients with pre- and post-tricuspid shunt. PMID- 26868161 TI - Early-onset Parkinson disease leading to diagnosis of 22q11.2 deletion syndrome. PMID- 26868162 TI - Dissolved atmospheric gas in xylem sap measured with membrane inlet mass spectrometry. AB - A new method is described for measuring dissolved gas concentrations in small volumes of xylem sap using membrane inlet mass spectrometry. The technique can be used to determine concentrations of atmospheric gases, such as argon, as reported here, or for any dissolved gases and their isotopes for a variety of applications, such as rapid detection of trace gases from groundwater only hours after they were taken up by trees and rooting depth estimation. Atmospheric gas content in xylem sap directly affects the conditions and mechanisms that allow for gas removal from xylem embolisms, because gas can dissolve into saturated or supersaturated sap only under gas pressure that is above atmospheric pressure. The method was tested for red trumpet vine, Distictis buccinatoria (Bignoniaceae), by measuring atmospheric gas concentrations in sap collected at times of minimum and maximum daily temperature and during temperature increase and decline. Mean argon concentration in xylem sap did not differ significantly from saturation levels for the temperature and pressure conditions at any time of collection, but more than 40% of all samples were supersaturated, especially during the warm parts of day. There was no significant diurnal pattern, due to high variability between samples. PMID- 26868163 TI - Aldose reductase participates in the downregulation of T cell functions due to suppressor macrophages. AB - The cell-to-cell contact of T lymphocytes with immunosuppressive macrophages causes marked changes in the tyrosine phosphorylation of some cytosolic proteins of T cells. By phosphoproteome analysis, we identified a 36-kDa protein as aldose reductase (AR). The AR expression in T cells was not changed by TCR stimulation or due to cell-to-cell transmission of suppressor signals from immunosuppressive macrophages. Therefore, AR phosphorylation/dephosphorylation is essential for the transduction of TCR-mediated T-cell stimulatory signals, and moreover plays important roles for the cross-talk of immunosuppressive macrophage-derived suppressor signals with the signaling pathways for T-cell activation. Moreover, AR played important roles in the upregulation of ERK1/2-mediated signaling pathways in T lymphocytes. Notably, the enzymatic activity of AR was not required for its signaling action. Taken together, it is concluded that AR mediates intracellular transmission of the suppressor signal of immunosuppressive macrophages toward downstream ERK1/2 pathways, possibly through its direct interaction with acceptor proteins. PMID- 26868165 TI - Huge pseudomyxoma peritonei: Surgical strategies and procedures to employ to optimize the rate of complete cytoreductive surgery. AB - BACKGROUND: Complete cytoreductive surgery (CCRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the best-known treatment for pseudomyxoma peritonei (PMP). In 30% of the cases, PMP realize a widespread involvement of the peritoneal cavity. In these extreme situations, we developed, devoted strategies to optimize the feasibility and safety of CCRS. This study describes the surgical resections required for CCRS and the consequent approaches that we propose to achieve CCRS. MATERIALS AND METHODS: We defined "huge PMP" by a peritoneal cancer index (PCI) >= 28. Surgical procedures of patients operated on between 1994 and 2014 were retrospectively reviewed from a prospective database in a single institution. RESULTS: During this period, 311 patients were operated on and 247 (79%) underwent CCRS + HIPEC. Among them, 100 patients presented "huge" PMP and 54 patients underwent CCRS + HIPEC. In patients with "huge" PMP, the rate of CCRS + HIPEC was 25% before 2002 and reached 71% between 2011 and 2014. We identified 3 conditions for CCRS 1) to guaranty a sufficient length of residual small bowel 2) to preserve the left gastric vessels in order to preserve the superior third of the stomach 3) to ensure that the hepatic pedicle can be entirely cleared from its tumor involvement. None of the other peritonectomy procedures were decisional for CCRS. CONCLUSION: Our learning curve improved the selection and completion rate of CCRS + HIPEC for "huge PMP". Some anatomical and physiological prerequisites guarantee the feasibility and safety of such extensive surgeries. PMID- 26868166 TI - The role of palliative surgery in the management of advanced pancreatic cancer in patients with biliary and duodenal obstruction. PMID- 26868164 TI - Activation and inhibition of tph2 serotonergic neurons operate in tandem to influence larval zebrafish preference for light over darkness. AB - Serotonergic neurons have been implicated in a broad range of processes, but the principles underlying their effects remain a puzzle. Here, we ask how these neurons influence the tendency of larval zebrafish to swim in the light and avoid regions of darkness. Pharmacological inhibition of serotonin synthesis reduces dark avoidance, indicating an involvement of this neuromodulator. Calcium imaging of tph2-expressing cells demonstrates that a rostral subset of dorsal raphe serotonergic neurons fire continuously while the animal is in darkness, but are inhibited in the light. Optogenetic manipulation of tph2 neurons by channelrhodopsin or halorhodopsin expression modifies preference, confirming a role for these neurons. In particular, these results suggest that fish prefer swimming in conditions that elicits lower activity in tph2 serotonergic neurons in the rostral raphe. PMID- 26868167 TI - Nipple-areola complex reconstruction techniques: A literature review. AB - Many techniques for nipple-areola complex (NAC) reconstruction are described. Clarity is required on the currently available options. Since a complete list of all the techniques described until now is not available, a possibly comprehensive literature overview was carried out from 75 papers (years 1946-2015). The local flap was the most frequently described technique for the nipple reconstruction with no significant difference in complications' rate among the various types of techniques. Complications in nipple reconstruction were 46.9% after graft, 7.9% after local flap, and 5.3% in case of flaps with autologous graft/alloplastic/allograft augmentation, while complications in areola reconstruction were 10.1% after graft, and 1.6% after areola tattoo. Flaps appear to be more reliable than grafts in nipple reconstruction, while tattoo is thought to be safer than graft in areola reconstruction. The loss of projection, although considerable (45%-75%), had not significant impact on patients' satisfaction. Due to contraction, overcorrection of 25-50% of the desired result is advisory when adopting local flaps, in order to prevent loss of projection. The use of flaps with autologous graft/alloplastic/allograft augmentation (cartilage, fat, calcium hydroxylapatite, acellular dermal matrix, polymethylmethacrylate, biologic collagen) showed a minor loss of nipple projection but may expose to a relative increased number of postoperative flap necrosis. PMID- 26868168 TI - Surgical result of pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation. AB - BACKGROUND/PURPOSE: To report the recurrence rate and cosmetic results of conjunctival wound edge and caruncle, and complications after pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation. METHODS: A prospective interventional cohort study enrolled 57 (58 eyes) patients undergoing pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation. All patients received postoperative follow-up for at least 12 months. Recurrence rate was graded from 1 to 4, and cosmetic results of conjunctival edge and caruncle were graded from 1 to 5. RESULTS: The cohort included 48 eyes with nasal pterygium, 5 eyes with temporal pterygium, and 5 eyes with double pterygium. There were 81.0% (n=47), 0% (n=0), 12% (n=7), and 7% (n=4) of eyes with Grades 1-4 recurrence, respectively. The cosmetic results of conjunctival wound edge and caruncle in cases with nasal pterygium showed 59.3% (n=32), 14.8% (n=8), 9.3% (n=5), 16.6% (n=9), and 0% (n=0) of eyes with Grades 1 5 morphology, respectively. Overall, 5.1% (n=3), 3.4% (n=2), 3.4% (n=2), 3.4% (n=2), 1.7% (n=1), 6.9% (n=4), and 1.7% (n=1) of patients suffered from postoperative pyogenic granuloma, transient diplopia, permanent motility restriction, steroid glaucoma, fat prolapse, subamniotic membrane hemorrhage, and early detachment of amniotic membrane, respectively. CONCLUSION: Pterygium extended removal followed by fibrin glue-assisted amniotic membrane transplantation results in low recurrence, satisfactory cosmetic results and a low incidence of additional complications. PMID- 26868169 TI - Presence of subpleural pulmonary interstitial emphysema as an indication of single or multiple alveolar ruptures on CT in patients with spontaneous pneumomediastinum. AB - Background There are no previous reports regarding the computed tomography (CT) findings of subpleural pulmonary interstitial emphysema (PIE) in patients with spontaneous pneumomediastinum. Purpose To evaluate CT findings of subpleural PIE that may indicate a direct site of terminal alveolar rupture. Material and Methods We retrospectively evaluated chest CT and the medical records of 34 patients with spontaneous pneumomediastinum. Subpleural PIE was defined as the presence of an interstitial air collection in the subpleural portion of the lungs excluding the bronchovascular bundle. Results Subpleural PIE on CT was identified in six of 34 patients (17.6%) with spontaneous pneumomediastinum. In four of these (66.7%), subpleural PIE was present in multiple lobes suggesting multiple simultaneous ruptures of terminal alveoli. The shape of subpleural PIE was elongated linear (4/6), branching and linear (1/6), and elliptical (1/6). Conclusion The presence of subpleural PIE on CT suggests an origin of pneumomediastinal air from alveolar rupture. PMID- 26868170 TI - Duplicate publications: attack of the clones. PMID- 26868171 TI - Mesenteric panniculitis: review of consecutive abdominal MDCT examinations with a matched-pair analysis. AB - Background The relationship between mesenteric panniculitis (MP), a benign condition involving adipose mesenteric tissue, and malignancy is still being questioned. Purpose To investigate the prevalence of MP and study its relationship with malignancy. To investigate the 5-year outcome of MP patients for the development of malignancy. Material and Methods Retrospective search for MP reviewing 3054 consecutive multidetector row computed tomography (MDCT) scans. Two radiologists in consensus selected the final MP population. For each MP, two subsequent MDCT scans of patients matched by gender and age. Five-year follow-up data regarding cancer occurrence after index MDCT scans were obtained for the MP and control groups. Comparisons between groups were performed using univariate conditional logistic regression. Results A total of 160 patients had at least three of the five MDCT features defining MP. Sixty-four were excluded owing to disease causing mesenteric infiltration or contiguous neoplastic involvement. The final population included 96 MP and 192 control patients. The prevalence of MP was 3.14%. Most cases of MP were discrete (66.7%), 2.1% were marked. In total, 60.4% and 59.4% of MP and control patients, respectively, had cancer ( P = 0.86). There was no significant association between MP score and presence of cancer ( P = 0.06) nor any relationship between the course of associated cancer and MP evolution. In total, 80/96 MP patients and 50/78 control patients without associated cancer had a 5-year follow-up at least. No significant difference between both groups for new tumor occurrence during follow-up was found ( P = 0.15). Conclusion Our results do not suggest that patients with incidentally found MP should be followed up for early detection of a cancer. PMID- 26868172 TI - Oral distension methods for small bowel MRI: comparison of different agents to optimize bowel distension. AB - Background Different methods for bowel distension prior to magnetic resonance imaging (MRI) examinations were described in recent years. Purpose To compare orally administered psyllium or locust bean gum / mannitol (LBM) with tylose administered through a duodenal catheter for bowel distension in patients undergoing MRI examination of the small bowel. Material and Methods Three different methods of bowel distension prior to MRI were compared: tylose applied through a duodenal catheter and orally administered psyllium and LBM in three groups with 15 patients each. Datasets were blinded and reviewed independently by two experienced radiologists, who assessed the diagnostic value and the maximum luminal diameter. Results Tylose was superior to psyllium and LBM in the examination of the duodenum and proximal jejunum. LBM was superior to the other methods for distension of the ileum and terminal ileum. The greatest luminal diameter of the duodenum was achieved after tylose and distension of the terminal ileum was the best in patients receiving LBM. The psyllium group was inferior to the other two groups in all segments. Conclusion By using LBM as an oral method of bowel distension, many patients can avoid the unpleasant placement of a duodenal catheter without compromising the diagnostic value of the examination. PMID- 26868173 TI - Surface modification of 3D-printed porous scaffolds via mussel-inspired polydopamine and effective immobilization of rhBMP-2 to promote osteogenic differentiation for bone tissue engineering. AB - For tissue engineering, a bio-porous scaffold which is applied to bone-tissue regeneration should provide the hydrophilicity for cell attachment as well as provide for the capability to bind a bioactive molecule such as a growth factor in order to improve cell differentiation. In this work, we prepared a three dimensional (3D) printed polycaprolactone scaffold (PCLS) grafted with recombinant human bone morphogenic protein-2 (rhBMP2) attached via polydopamine (DOPA) chemistry. The DOPA coated PCL scaffold was characterized by contact angle, water uptake, and X-ray photoelectron spectroscopy (XPS) in order to certify that the surface was successfully coated with DOPA. In order to test the loading and release of rhBMP2, we examined the release rate for 28days. For the In vitro cell study, pre-osteoblast MC3T3-E1 cells were seeded onto PCL scaffolds (PCLSs), DOPA coated PCL scaffold (PCLSD), and scaffolds with varying concentrations of rhBMP2 grafted onto the PCLSD 100 and PCLSD 500 (100 and 500ng/ml loaded), respectively. These scaffolds were evaluated by cell proliferation, alkaline phosphatase activity, and real time polymerase chain reaction with immunochemistry in order to verify their osteogenic activity. Through these studies, we demonstrated that our fabricated scaffolds were well coated with DOPA as well as grafted with rhBMP2 at a quantity of 22.7+/-5ng when treatment with 100ng/ml rhBMP2 and 153.3+/-2.4ng when treated with 500ng/ml rhBMP2. This grafting enables rhBMP2 to be released in a sustained pattern. In the in vitro results, the cell proliferation and an osteoconductivity of PCLSD 500 groups was greater than any other group. All of these results suggest that our manufactured 3D printed porous scaffold would be a useful construct for application to the bone tissue engineering field. STATEMENT OF SIGNIFICANCE: Tissue-engineered scaffolds are not only extremely complex and cumbersome, but also use organic solvents which can negatively influence cellular function. Thus, a rapid, solvent-free method is necessary to improve scaffold generation. Recently, 3D printing such as a rapid prototyping technique has several benefits in that manufacturing is a simple process using computer aided design and scaffolds can be generated without using solvents. In this study, we designed a bio-active scaffold using a very simple and direct method to manufacture DOPA coated 3D PCL porous scaffold grafted with rhBMP2 as a means to create bone tissue regenerative scaffolds. To our knowledge, our approach can allow for the generation of scaffolds which possessed good properties for use as bone-tissue scaffolds. PMID- 26868174 TI - Oxidation-Induced Degradable Nanogels for Iron Chelation. AB - Iron overload can increase cellular oxidative stress levels due to formation of reactive oxygen species (ROS); untreated, it can be extremely destructive to organs and fatal to patients. Since elevated oxidative stress levels are inherent to the condition in such patients, oxidation-induced degradable nanogels for iron chelation were rationally designed by simultaneously polymerizing oxidation sensitive host-guest crosslinkers between beta-cyclodextrin (beta-CD) and ferrocene (Fc) and iron chelating moieties composed of deferoxamine (DFO) into the final gel scaffold in reverse emulsion reaction chambers. UV-Vis absorption and atomic absorption spectroscopy (AAS) was used to verify iron chelating capability of nanogels. These materials can degrade into smaller chelating fragments at rates proportional to the level of oxidative stress present. Conjugating DFO reduces the cytotoxicity of the chelator in the macrophage cells. Importantly, the nanogel can effectively reduce cellular ferritin expression in iron overloaded cells and regulate intracellular iron levels at the same time, which is important for maintaining a homeostatic level of this critical metal in cells. PMID- 26868175 TI - Crystal structure of translation initiation factor 5B from the crenarchaeon Aeropyrum pernix. AB - Initiation factor 5B (IF5B) is a universally conserved translational GTPase that catalyzes ribosomal subunit joining. In eukaryotes, IF5B directly interacts via a groove in its domain IV with initiation factor 1A (IF1A), another universally conserved initiation factor, to accomplish efficient subunit joining. Here, we have determined the first structure of a crenarchaeal IF5B, which revealed that the archaea-specific region of IF5B (helix alpha15) binds and occludes the groove of domain IV. Therefore, archaeal IF5B cannot access IF1A in the same manner as eukaryotic IF5B. This fact suggests that different relationships between IF5B and IF1A exist in archaea and eukaryotes. PMID- 26868176 TI - A family matter--when a parent is diagnosed with multiple sclerosis. A qualitative study. AB - AIMS AND OBJECTIVES: The aim was to explore and describe from a triple perspective--that of the ill parent, the healthy parent and the children- experienced issues that are important to acknowledge and act upon to make it easier for a child to cope when a parent is diagnosed with multiple sclerosis. BACKGROUND: A chronic disease affects the whole family and has a substantial impact on the children. Traditionally, the focus is on the patient, and communication with other family members is not generally integrated into health care. Health care professionals need to be aware of a child's needs when a parent is diagnosed with multiple sclerosis. DESIGN: A qualitative design using content analysis with an inductive approach was used. METHODS: Nine focus group interviews were conducted with the ill parents, the healthy parents and the children separately. RESULTS: Participants jointly indicated that family members need to be recognised, both initially and onwards in their everyday lives. Seven categories were defined: Prerequisites within the families, Initial reactions, Trying to adapt and manage, Developing strategies, Everyday life, Thoughts about the future and Support from health care providers. Together they constituted the theme that multiple sclerosis is a family matter. Both ill and healthy parents wished for support from health care professionals in addressing their children's needs. CONCLUSIONS: Health care professionals need to pay attention to children as a parent's illness affects them. Not only the children would benefit, but so would their parents, as their worries for their children would be reduced. RELEVANCE TO CLINICAL PRACTICE: Staff can be advised to pay attention to the parenting role, how the parenting role and parent-child relationship may change as a result of a chronic disease. Parents may need reassurance and benefit from advice about how to talk to their children about their condition and its impact. PMID- 26868177 TI - Aspirin and colorectal cancer: the promise of precision chemoprevention. AB - Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action. PMID- 26868178 TI - Gene expression profiling of white adipose tissue reveals paternal transmission of proneness to obesity. AB - Previously, we found that C57BL/6J (B6) mice are more prone to develop obesity than PWK mice. In addition, we analyzed reciprocal crosses between these mice and found that (PWK * B6) F1 mice, which have B6 fathers, are more likely to develop dietary obesity than (B6 * PWK) F1 mice, which have B6 mothers. These results suggested that diet-induced obesity is paternally transmitted. In this study, we performed transcriptome analysis of adipose tissues of B6, PWK, (PWK * B6) F1, and (B6 * PWK) F1 mice using next-generation sequencing. We found that paternal transmission of diet-induced obesity was correlated with genes involved in adipose tissue inflammation, metal ion transport, and cilia. Furthermore, we analyzed the imprinted genes expressed in white adipose tissue (WAT) and obesity. Expression of paternally expressed imprinted genes (PEGs) was negatively correlated with body weight, whereas expression of maternally expressed imprinted genes (MEGs) was positively correlated. In the obesity-prone B6 mice, expression of PEGs was down-regulated by a high-fat diet, suggesting that abnormally low expression of PEGs contributes to high-fat diet-induced obesity in B6 mice. In addition, using single-nucleotide polymorphisms that differ between B6 and PWK, we identified candidate imprinted genes in WAT. PMID- 26868180 TI - Cerebral functional connectivity and Mayer waves in mice: Phenomena and separability. AB - Resting-state functional connectivity is a growing neuroimaging approach that analyses the spatiotemporal structure of spontaneous brain activity, often using low-frequency (<0.08 Hz) hemodynamics. In addition to these fluctuations, there are two other low-frequency hemodynamic oscillations in a nearby spectral region (0.1-0.4 Hz) that have been reported in the brain: vasomotion and Mayer waves. Despite how close in frequency these phenomena exist, there is little research on how vasomotion and Mayer waves are related to or affect resting-state functional connectivity. In this study, we analyze spontaneous hemodynamic fluctuations over the mouse cortex using optical intrinsic signal imaging. We found spontaneous occurrence of oscillatory hemodynamics ~0.2 Hz consistent with the properties of Mayer waves reported in the literature. Across a group of mice (n = 19), there was a large variability in the magnitude of Mayer waves. However, regardless of the magnitude of Mayer waves, functional connectivity patterns could be recovered from hemodynamic signals when filtered to the lower frequency band, 0.01-0.08 Hz. Our results demonstrate that both Mayer waves and resting-state functional connectivity patterns can co-exist simultaneously, and that they can be separated by applying bandpass filters. PMID- 26868181 TI - Low generation polyamine dendrimers bearing flexible tetraethylene glycol as nanocarriers for plasmids and siRNA. AB - Low G1 generation polyamine dendrimers built around programmable, flexible, and short tetraethyleneglycol branches were readily prepared in a divergent manner using a combination of orthogonal AB3 or AB5 units and highly efficient chemical transformations based on Cu(i) catalyzed alkyne-azide cycloaddition (CUAAC) and thiol-ene click reactions. The constructs showed that the G1 polyamines with only twelve and eighteen amine surface groups can successfully deliver siRNA in human cells, with transfection efficiency comparable to that of Lipofectamine 2000(r). Measurements of cell viability following transfection of plasmid DNA and siRNA showed that the dendritic polyamines are less cytotoxic than Lipofectamine 2000(r) and are thus preferable for biological applications. PMID- 26868182 TI - The role of maternal cardiac vagal control in the association between depressive symptoms and gestational hypertension. AB - Reduced cardiac vagal control, indexed by relatively lower high-frequency heart rate variability (HF-HRV), is implicated in depressed mood and hypertensive disorders among non-pregnant adults whereas research in pregnancy is limited. This study examined whether maternal HF-HRV during pregnancy mediates the association between depressed mood and gestational hypertension. Depressive symptoms (Edinburgh Depression Scale) and HF-HRV were measured during early (M=14.9 weeks) and late (M=32.4 weeks) pregnancy in 287 women. Gestational hypertension was determined by chart review. Depressive symptoms were associated with less HF-HRV (b=-0.02, p=.001). There was an indirect effect of depressed mood on gestational hypertension through late pregnancy HF-HRV (b=0.04, 95% CI 0.0038, 0.1028) after accounting for heart rate. These findings suggest cardiac vagal control is a possible pathway through which prenatal depressed mood is associated with gestational hypertension, though causal ordering remains uncertain. PMID- 26868184 TI - Caliber-Persistent Labial Artery: A Rarely Recognized Cause of a Lower Lip Swelling-Report of 5 Cases and Review of the Literature. AB - BACKGROUND: Caliber-persistent labial artery (CPLA) is a vascular anomaly of the labial artery that penetrates into the submucosa of the lip without reduction in diameter. It commonly presents as a bluish or normal-colored elevated mass and usually pulsates on manual palpation. It can resemble a mucocele or squamous cell carcinoma if surface ulceration presented. CPLA carries the risk of profuse bleeding if the artery undergoes transection during biopsy. METHODOLOGY: Five patients aged between 28 and 88 years presented with discrete lesions of the lower lip. All cases were diagnosed clinically as either mucocele or squamous cell carcinoma and were treated with excisional biopsy. RESULTS: The specimens showed a prominent muscular vessel in the stroma that was associated with ulceration in 2 cases. Hemostasis was achieved by either application of surgical diathermy or ligation with deep sutures at the wound area. Persistence of the lesion after excision was seen in only 1 case, another single case the patient complained of persistent paresthesia at the surgical site at 7 months review after biopsy. CONCLUSION: CPLA should be considered in the differential diagnosis of any raised soft tissue lesion affecting the lip. Careful inspection with palpation for pulse during clinical examination should permit an accurate clinical diagnosis and may prevent unnecessary surgical treatment or prepare the operator for the possibility of hemorrhage during surgery. Pathologists can be alerted to the possibility of CPLA where an isolated muscular vessel is encountered during lip biopsy. PMID- 26868183 TI - Custom-Machined Miniplates and Bone-Supported Guides for Orthognathic Surgery: A New Surgical Procedure. AB - PURPOSE: Several surgical strategies exist to improve accuracy in orthognathic surgery, but ideal planning and treatment have yet to be described. The purpose of this study was to present and assess the accuracy of a virtual orthognathic positioning system (OPS), based on the use of bone-supported guides for placement of custom, highly rigid, machined titanium miniplates produced using computer aided design and computer-aided manufacturing technology. MATERIALS AND METHODS: An institutional review board-approved prospective observational study was designed to evaluate our early experience with the OPS. The inclusion criteria were as follows: adult patients who were classified as skeletal Class II or III patients and as candidates for orthognathic surgery or who were candidates for maxillomandibular advancement as a treatment for obstructive sleep apnea. Reverse planning with computed tomography and modeling software was performed. Our OPS was designed to avoid the use of intermaxillary fixation and occlusal splints. The minimum follow-up period was 1 year. RESULTS: Six patients were enrolled in the study. The custom OPS miniplates fit perfectly with the anterior buttress of the maxilla and the mandible body surface intraoperatively. To evaluate accuracy, the postoperative 3-dimensional reconstructed computed tomography image and the presurgical plan were compared. In the maxillary fragments that underwent less than 6 mm of advancement, the OPS enabled an SD of 0.14 mm (92% within 1 mm) at the upper maxilla and 0.34 mm (86% within 1 mm) at the mandible. In the case of great advancements of more than 10 mm, the SD was 1.33 mm (66% within 1 mm) at the upper maxilla and 0.67 mm (73% within 1 mm) at the mandibular level. CONCLUSIONS: Our novel OPS was safe and well tolerated, providing positional control with considerable surgical accuracy. The OPS simplified surgery by being independent of support from the opposite maxilla and obviating the need for classic intermaxillary occlusal splints. PMID- 26868186 TI - The alpha4beta2 nicotinic acetylcholine receptor modulates autism-like behavioral and motor abnormalities in pentylenetetrazol-kindled mice. AB - Epilepsy is associated with several psychiatric disorders, including cognitive impairment, autism and attention deficit/hyperactivity disorder (ADHD). However, the psychopathology of epilepsy is frequently unrecognized and untreated in patients. In the present study, we investigated the effects of ABT-418, a neuronal nicotinic acetylcholine receptor agonist, on pentylenetetrazol (PTZ) kindled mice with behavioral and motor abnormalities. PTZ-kindled mice displayed impaired motor coordination (in the rotarod test), anxiety (in the elevated plus maze test) and social approach impairment (in the three-chamber social test) compared with control mice. ABT-418 treatment (0.05 mg/kg, intraperitoneally) alleviated these behavioral abnormalities in PTZ-kindled mice. Immunolabeling of tissue sections demonstrated that expression of the alpha4 nicotinic acetylcholine receptor subunit in the medial habenula was similar in control and PTZ-kindled mice. However, expression was significantly decreased in the piriform cortex in PTZ-kindled mice. In addition, we examined the expression of the synaptic adhesion molecule neuroligin 3 (NLG3). NLG3 expression in the piriform cortex was significantly higher in PTZ-kindled mice compared with control mice. Collectively, our findings suggest that ADHD-like or autistic-like behavioral abnormalities associated with epilepsy are closely related to the downregulation of the alpha4 nicotinic receptor and the upregulation of NLG3 in the piriform cortex. In summary, this study indicates that ABT-418 might have therapeutic potential for attentional impairment in epileptic patients with psychiatric disorders such as autism and ADHD. PMID- 26868187 TI - IkappaB kinase beta inhibitor, IMD-0354, prevents allergic asthma in a mouse model through inhibition of CD4(+) effector T cell responses in the lung-draining mediastinal lymph nodes. AB - IkappaB kinase (IKK) is important for nuclear factor (NF)-kappaB activation under inflammatory conditions. It has been demonstrated that IMD-0354, i.e. a selective inhibitor of IKKbeta, inhibited allergic inflammation in a mouse model of ovalbumin (OVA)-induced asthma. The present study attempts to shed light on the involvement of CD4(+) effector (Teff) and regulatory (Treg) T cells in the anti asthmatic action of IMD-0354. The animals were divided into three groups: vehicle treated, PBS-sensitized/challenged mice (PBS group); vehicle treated, OVA sensitized/challenged mice (OVA group); and IMD-0354-treated, OVA sensitized/challenged mice. The analyzed parameters included the absolute counts of Treg cells (Foxp3(+)CD25(+)CD4(+)), activated Teff cells (Foxp3( )CD25(+)CD4(+)) and resting T cells (CD25(-)CD4(+)) in the mediastinal lymph nodes (MLNs), lungs and peripheral blood. Moreover, lung histopathology was performed to evaluate lung inflammation. It was found that the absolute number of cells in all studied subsets was considerably increased in the MLNs and lungs of mice from OVA group as compared to PBS group. All of these effects were fully prevented by treatment with IMD-0354. Histopathological examination showed that treatment with IMD-0354 protected the lungs from OVA-induced allergic airway inflammation. Our results indicate that IMD-0354 exerts anti-asthmatic action, at least partially, by blocking the activation and clonal expansion of CD4(+) Teff cells in the MLNs, which, consequently, prevents infiltration of the lungs with activated CD4(+) Teff cells. The beneficial effects of IMD-0354 in a mouse model of asthma are not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of inducible Treg cells. PMID- 26868185 TI - Predicting malaria vector distribution under climate change scenarios in China: Challenges for malaria elimination. AB - Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control activities for sustaining elimination and preventing reintroduction of malaria. In China, however, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of climate change on four dominant malaria vectors (An. dirus, An. minimus, An. lesteri and An. sinensis) using species distribution models for two future decades: the 2030 s and the 2050 s. Simulation-based estimates suggest that the environmentally suitable area (ESA) for An. dirus and An. minimus would increase by an average of 49% and 16%, respectively, under all three scenarios for the 2030 s, but decrease by 11% and 16%, respectively in the 2050 s. By contrast, an increase of 36% and 11%, respectively, in ESA of An. lesteri and An. sinensis, was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios. in the 2050 s. In total, we predict a substantial net increase in the population exposed to the four dominant malaria vectors in the decades of the 2030 s and 2050 s, considering land use changes and urbanization simultaneously. Strategies to achieve and sustain malaria elimination in China will need to account for these potential changes in vector distributions and receptivity. PMID- 26868179 TI - In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use. AB - The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This "blood-brain barrier" function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood-brain barrier models with a focus on their validation regarding a set of well-established blood-brain barrier characteristics. As an ideal cell culture model of the blood-brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described. PMID- 26868188 TI - Pharmacokinetics of Paradol Analogues Orally Administered to Rats. AB - The kinetics parameters of paradols with different acyl chain lengths have been evaluated to determine their antiobesity site of action. Rats were orally administered olive oil containing 0-, 6-, 8-, or 12-paradol, and blood samples were collected at different time points. The concentrations of the paradols in the plasma were analyzed both with and without beta-glucuronidase treatment. The area under the plasma concentration-time curve from 0 to 24 h (AUC(0-24h)) of the parent compounds decreased with increasing acyl chain length. Whereas 12-paradol showed the largest AUC(0-24h) with the longest time to reach its maximum plasma concentration of all of the compounds tested, the AUC(0-24h) values of the metabolites decreased with increasing acyl chain length. These results indicate that increasing acyl chain length leads to a decrease in the absorption of paradols via the intestinal tract, the wall of which was estimated to be their antiobesity site of action. PMID- 26868190 TI - FACTORS INFLUENCING REIMBURSEMENT OF MEDICAL DEVICES IN FRANCE. AB - OBJECTIVES: This study aims to analyze the key factors considered for the first application of the National Committee for the Evaluation of Medical Devices (CNEDiMTS) for achieving reimbursement through registration in the list of products and services qualifying for reimbursement (LPPR). METHODS: All the appraisals studied on medical devices (MD) for first inclusion in the LPPR during 2011 and 2012 were retrieved from the French National Authority for Health or Haute Autorite de sante (HAS) Web site. A list of relevant factors was analyzed for each included opinion, followed by univariate and multivariate analyses to highlight the key factors that impacted the expected benefit (EB) provided by HAS. RESULTS: A total of 151 appraisals were included in the study. Of them, 94 (62 percent) were granted with sufficient EB. The manufacturers were mostly from the United States (36 percent), while most of the applicants were from France (84 percent). After adjusting for other retrieved factors, it was observed that MDs complying with the technical standards, requests supported by opinion(s) from previous generation of MD, and the presence of recommendations or guidelines had more probability to obtain a sufficient EB. A lower probability was related to MDs supported by low-quality studies and with no specific health public benefit. CONCLUSIONS: Our results confirmed that manufacturers seeking reimbursement should be aware of the expectations of the health authorities (level of evidence, technical standard, etc.) and foresee their plan of sending requests for funding so that they can provide evidence of good quality. PMID- 26868191 TI - Purification and characterization of R-stereospecific amidase from Brevibacterium epidermidis ZJB-07021. AB - A R-stereospecific amidase was purified from Brevibacterium epidermidis ZJB-07021 and characterized in detail. The amidase was purified to homogeneity by three chromatographic steps for up to 328.9-fold with specific activity of 31.9 U mg( 1). The enzyme was a homodimer with a molecular mass of 94 kDa. It exhibited maximum activity at 40 degrees C and pH 7.5. The enzyme was strongly inactivated by serine protease inhibitor PMSF. The values of Km and Vmax for racemic 2,2 dimethylcyclopropane carboxamide (DMCPCA) were 4.58 mM and 35.03 MUmol min(-1) mg(-1) protein, respectively. The amidase showed a broad substrate spectrum toward aliphatic, aromatic and heterocyclic amides, but could hardly hydrolyze the bulky side-chain-containing amides. Furthermore, kinetic resolution of racemic DMCPCA by the amidase afforded S-DMCPCA in 46.3% yield and 99% ee with an average E-value of 67. These unique properties of the amidase imply that it is a promising biocatalyst for the production of chiral amides and carboxylic acids. PMID- 26868192 TI - Efficient Charge Separation between Bi and Bi2 MoO6 for Photoelectrochemical Properties. AB - Herein, porous Bi/Bi2 MoO6 nanoparticles have been prepared by a facile in-situ reduction approach. Moreover, the morphology and Bi content of product could be controlled by varying the reaction time. By controlled fabrication, the desired porous Bi2 MoO6 nanostructure with incorporation of Bi was obtained and exhibited high photoelectric and photocatalytic activity. In particular, the samples yield a photocurrent density of 320 MUA cm(-2) , which is 3.2 times that of the pure Bi2 MoO6 nanosheet (100 MUA cm(-2) ) under the same conditions. UV/Vis diffuse reflectance spectroscopy analysis confirmed the surface plasmon resonance in the as-prepared porous nanoparticles. The improved photoelectric properties could be the synergistic effect of the porous structure with large surface area and effective electron-hole separations between Bi and Bi2 MoO6 . PMID- 26868189 TI - Japan Prosthodontic Society position paper on "occlusal discomfort syndrome". AB - PURPOSE: Dentists may encounter patients who present with a sense of a malocclusion but in whom no objective findings can be detected. For the patient who insists that there is occlusal discomfort, in the absence of evidence some dentists elect to perform an occlusal adjustment that not only fails to alleviate symptoms, and may, in fact, exacerbate the discomfort. The patient-dentist relationship is then likely compromised because of a lack of trust. STUDY SELECTION: In 2011, the Clinical Practice Guidelines Committee of the Japan Prosthodontic Society formulated guidelines for the management of occlusal discomfort. When formulating clinical practice guidelines, the committee bases their recommendations on information derived from scientific evidence. For "occlusal dysesthesia," however, there are an insufficient number of high-quality papers related to the subject. Therefore, a consensus meeting was convened by the Japan Prosthodontic Society to examine evidence in the Japanese- and English language literature and generate a multi-center survey to create an appropriate appellation for this condition. RESULTS: As a result of the consensus meeting and survey findings, this condition may be justifiably termed "occlusal discomfort syndrome." CONCLUSIONS: The Japan Prosthodontics Society believes that identification of an umbrella term for occlusal discomfort might serve as a useful guide to formulating clinical practice guidelines in the future. This position paper represents summary findings in the literature combined with the results of a multicenter survey focused on dental occlusal treatment and the condition of patients who present with occlusal discomfort syndrome. PMID- 26868193 TI - David Beran: the battle for 100% access to insulin. PMID- 26868194 TI - PCSK9 inhibition in type 2 diabetes: so far so good, but not there yet. PMID- 26868196 TI - Culture and medical psychiatric narratives. PMID- 26868195 TI - Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data. AB - BACKGROUND: Patients with type 2 diabetes have increased cardiovascular risk. PCSK9 monoclonal antibodies have been shown to reduce LDL cholesterol and other lipids, but specific efficacy for patients with diabetes is unknown. We compared the effect of the PCSK9 inhibitor evolocumab on lipid parameters in patients with and without type 2 diabetes. METHODS: We did a random-effects meta-analysis of randomised clinical trials comparing the efficacy of evolocumab, placebo, and ezetimibe to improve lipid parameters in adult patients (age 18-80 years) with or without type 2 diabetes. We searched MEDLINE and Embase to identify eligible 12 week, phase 3 trials published between Jan 1, 2012, and Feb 28, 2015. We excluded trials that included patients who had homozygous familial hypercholesterolaemia. All analyses were based on individual participant data. We used DerSimonian and Laird random-effects meta-analyses to compare the mean changes from baseline in concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol, triglycerides, lipoprotein(a), and HDL cholesterol at 12 weeks for evolocumab, placebo, and ezetimibe. We also assessed the effect of evolocumab therapy compared with placebo across subgroups of patients based on glycaemia, insulin use, renal function, and cardiovascular disease status at baseline. RESULTS: Three trials met our inclusion criteria, and included 413 patients with type 2 diabetes and 2119 patients without type 2 diabetes. In patients with type 2 diabetes evolocumab caused mean reductions in LDL cholesterol concentration that were 60% (95% CI 51-69) versus placebo and 39% (32-47) versus ezetimibe. In patients without type 2 diabetes, evolocumab caused mean reductions in LDL cholesterol that were 66% (62-70) versus placebo and 40% (36-45) versus ezetimibe. In patients with type 2 diabetes, evolocumab was associated with reductions in non-HDL cholesterol (55% [47-63] vs placebo and 34% [26-41] vs ezetimibe), total cholesterol (38% [32-44] vs placebo and 24% [16-31] vs ezetimibe), and lipoprotein(a) (31% [25-37] vs placebo and 26% [16-35] vs ezetimibe), and an increase in HDL cholesterol (7% [4-11] vs placebo and 8% [4 13] vs ezetimibe). Findings were similar across diabetes subgroups based on glycaemia, insulin use, renal function, and cardiovascular disease status. INTERPRETATION: Evolocumab markedly reduces atherogenic lipoproteins in patients with type 2 diabetes, an effect that is consistent across subgroups and similar to that seen in patients without type 2 diabetes. Results from ongoing cardiovascular outcome trials of PCSK9 inhibitors will provide additional data to inform the use of these drugs in patients with type 2 diabetes. FUNDING: Amgen. PMID- 26868197 TI - Sociosomatic theory in Vietnamese immigrants' narratives of distress. AB - We examined the symptom experience and illness explanations of Vietnamese immigrants to Canada through narratives collected during a study of pathways and barriers to mental health care. The narratives presented two culture-related explanatory models: phong thap and ua't u'c. Common elements in the narratives of those who suffered from ua't u'c were experiences of injustice and indignation, along with the persistent inability to denounce these injustices because of the sufferer's social status. In contrast, phong thap - an explanation analogous to rheumatism - was a socially acceptable way to describe distress that was attributed to depletion of energy, cold and environmental effects. Talk about phong thap also served as an idiom of distress that permitted older people to express negative feelings about their life situation in Canada in a socially acceptable way. The contrast between these models throws into relief the complex interaction of explanatory models and idioms of distress in the co-construction of narratives of distress. PMID- 26868198 TI - From chaos to cosmogeny. AB - Illness narratives are informed by grand metanarratives in any society. This paper compares and contrasts understandings of stories relating to illness among Western academics and Hasidic Jews. While not arguing for any historical continuity, both cultures are informed by core metanarratives of progress and ascendance. Contemporary Western society emphasizes coherence, success, progress, and movement. In Hasidism the universe is slowly progressing to a state of perfection. Storytelling in both cultures results in a process of restitution. In narrative theory it is the self which is repaired. In Hasidism it is the soul which is repaired through storytelling. How have narratives of misfortune changed since the atrocities of the Holocaust? PMID- 26868199 TI - Friendly fire. AB - From September 1990 to June 1991, the UK deployed 53,462 military personnel in the Gulf War. In 1993 reports began to surface in the UK about unexplained health problems occurring amongst Gulf War veterans. This paper considers the way sufferers of Gulf War Syndrome (GWS) came to label their condition in this way. Unlike other research into this illness, this work focuses on sufferers' own accounts to better understand the way GWS is perceived by those it affects. Based on 14 months of ethnographic fieldwork in the UK, data for this paper were collected mainly by in-depth semi-structured interviews with GWS sufferers, their family members, doctors and scientists, as well as Gulf veterans. Findings suggest that GWS narratives provide a template to make sense of life events and illness. Investigating the way veterans came to ascribe to GWS as an explanation of their suffering, it became clear that contact with other sufferers was central to this process. Through participation in the veterans group and by assimilating the stories of other sufferers, a culturally specific narrative form is learned. This provides a framework for the reflexive re-interpretation of one's past and helps to construct a narrative of GWS. Unlike most work on narrative which focuses on the individual, this interpretation suggests that the collective aspect is central. In the absence of a diagnostic test and a coherence of symptoms, it is the concordance between the individual and collective narrative that is persuasive. PMID- 26868200 TI - Not being mentally ill. AB - Much of the social scientific work on psychiatry and mental health, from a variety of competing perspectives, has focused upon power and the social construction of 'mental illness'. Very little attention has been paid to resistance or to the various ways in which 'patients' or 'survivors' (as some now prefer to refer to themselves) have sought to socially deconstruct 'mental illness'. This paper seeks to redress that balance by way of a detailed examination of some of the key practices of resistance which have developed within the context of the UK mental health survivors movement. Using key concepts from Bourdieu's theory of practice, it examines the challenge which survivors have mounted to the symbolic power of psychiatry, and the resistance habitus which their opposition has given rise to. PMID- 26868201 TI - Escape, enlightenment and endurance. AB - This paper reports findings from a study which analysed the narratives of individuals who described themselves as recovered or recovering from psychosis, a term referring to experiences such as hearing voices other people do not hear, seeing or sensing things other people do not see or sense, holding unusual beliefs (delusions) or beliefs about the malevolent intention of others which seem unwarranted (paranoia). A narrative approach was taken since it allows for a focus on the construction of meaning and it is the breakdown of shared meanings which, at least in part, defines psychotic experience. It was also anticipated that the way the individual narrated their experience would offer important clues as to how they (and others) had facilitated the recovery process. This paper reports on the analysis of genre, tone and core narratives. Three distinct genres emerged from the analysis: narratives of escape, enlightenment and endurance. There was a relationship between genre, tone and core narrative. The study raises questions about how psychosis is experienced, understood and treated by the individual, by mental health professionals and by society. PMID- 26868202 TI - Narrative expressions of despair under occupation. AB - As part of the first anthropological study on suicide in the contemporary Arab world, 31 suicide narratives from Palestinians living under Israeli occupation in the West Bank and Gaza were collected and analysed within their cultural, socio economic and political contexts. The sexual segregation of the mainly Muslim society was reflected in the different expressions of distress used in the female and male narratives. Women felt 'pressurized', 'suffocated', 'nervy', with their emotions about to explode. Their suicide attempts were spontaneous outbursts of emotional frustration. Men appeared 'worn out', 'tired', 'depressed' and dying seemed more honourable than living unable to gain status or even become a social adult male. These narratives of suffocation and frustration provide some understanding of reactions to the current dire political and economic situation faced by Palestinians living under siege as Israel uses ever more drastic measures to subdue the population. For suicide bombers, death may also seem more honourable than life under oppression. PMID- 26868205 TI - The Ethical Challenges of Compassionate Use. PMID- 26868206 TI - Demographic buffering and compensatory recruitment promotes the persistence of disease in a wildlife population. AB - Demographic buffering allows populations to persist by compensating for fluctuations in vital rates, including disease-induced mortality. Using long-term data on a badger (Meles meles Linnaeus, 1758) population naturally infected with Mycobacterium bovis, we built an integrated population model to quantify impacts of disease, density and environmental drivers on survival and recruitment. Badgers exhibit a slow life-history strategy, having high rates of adult survival with low variance, and low but variable rates of recruitment. Recruitment exhibited strong negative density-dependence, but was not influenced by disease, while adult survival was density independent but declined with increasing prevalence of diseased individuals. Given that reproductive success is not depressed by disease prevalence, density-dependent recruitment of cubs is likely to compensate for disease-induced mortality. This combination of slow life history and compensatory recruitment promotes the persistence of a naturally infected badger population and helps to explain the badger's role as a persistent reservoir of M. bovis. PMID- 26868207 TI - Extending FDA guidance to include consumer medication information (CMI) delivery on mobile devices. AB - This paper describes the current state of consumer-focused mobile health application use and the current U.S. Food and Drug Administration (FDA) guidance on the distribution of consumer medication information (CMI), and discusses recommendations and considerations for the FDA to expand CMI guidance to include CMI in mobile applications. Smartphone-based health interventions have been linked to increased medication adherence and improved health outcomes. Trends in smartphone ownership present opportunities to more effectively communicate and disseminate medication information; however, current FDA guidance for CMI does not outline how to effectively communicate CMI on a mobile platform, particularly in regards to user-centered design and information sourcing. As evidence supporting the potential effectiveness of mobile communication in health care continues to increase, CMI developers, regulating entities, and researchers should take note. Although mobile-based CMI offers an innovative mechanism to deliver medication information, caution should be exercised. Specifically, considerations for developing mobile CMI include consumers' digital literacy, user experience (e.g., usability), and the quality and accuracy of new widely used sources of information (e.g., crowd-sourced reviews and ratings). Recommended changes to FDA guidance for CMI include altering the language about scientific accuracy to address more novel methods of information gathering (e.g., anecdotal experiences and Google Consumer Surveys) and including guidance for usability testing of mobile health applications. PMID- 26868208 TI - Protective Role for B-1b B Cells and IgM in Obesity-Associated Inflammation, Glucose Intolerance, and Insulin Resistance. AB - OBJECTIVE: Little is known about the role(s) B cells play in obesity-induced metabolic dysfunction. This study used a mouse with B-cell-specific deletion of Id3 (Id3(Bcell KO)) to identify B-cell functions involved in the metabolic consequences of obesity. APPROACH AND RESULTS: Diet-induced obese Id3(Bcell KO) mice demonstrated attenuated inflammation and insulin resistance in visceral adipose tissue (VAT), and improved systemic glucose tolerance. VAT in Id3(Bcell KO) mice had increased B-1b B cells and elevated IgM natural antibodies to oxidation-specific epitopes. B-1b B cells reduced cytokine production in VAT M1 macrophages, and adoptively transferred B-1b B cells trafficked to VAT and produced natural antibodies for the duration of 13-week studies. B-1b B cells null for Id3 demonstrated increased proliferation, established larger populations in Rag1(-/-) VAT, and attenuated diet-induced glucose intolerance and VAT insulin resistance in Rag1(-/-) hosts. However, transfer of B-1b B cells unable to secrete IgM had no effect on glucose tolerance. In an obese human population, results provided the first evidence that B-1 cells are enriched in human VAT and IgM antibodies to oxidation-specific epitopes inversely correlated with inflammation and insulin resistance. CONCLUSIONS: NAb-producing B-1b B cells are increased in Id3(Bcell KO) mice and attenuate adipose tissue inflammation and glucose intolerance in diet-induced obese mice. Additional findings are the first to identify VAT as a reservoir for human B-1 cells and to link anti-inflammatory IgM antibodies with reduced inflammation and improved metabolic phenotype in obese humans. PMID- 26868209 TI - Glycosphingolipids on Human Myeloid Cells Stabilize E-Selectin-Dependent Rolling in the Multistep Leukocyte Adhesion Cascade. AB - OBJECTIVE: Recent studies suggest that the E-selectin ligands expressed on human leukocytes may differ from those in other species, particularly mice. To elaborate on this, we evaluated the impact of glycosphingolipids expressed on human myeloid cells in regulating E-selectin-mediated cell adhesion. APPROACH AND RESULTS: A series of modified human cell lines and primary neutrophils were created by targeting UDP-Glucose Ceramide Glucosyltransferase using either lentivirus-delivered shRNA or CRISPR-Cas9-based genome editing. Enzymology and mass spectrometry confirm that the modified cells had reduced or abolished glucosylceramide biosynthesis. Glycomics profiling showed that UDP-Glucose Ceramide Glucosyltransferase disruption also increased prevalence of bisecting N glycans and reduced overall sialoglycan expression on leukocyte N- and O-glycans. Microfluidics-based flow chamber studies demonstrated that both the UDP-Glucose Ceramide Glucosyltransferase knockouts and knockdowns display ~60% reduction in leukocyte rolling and firm adhesion on E-selectin bearing stimulated endothelial cells, without altering cell adhesion to P-selectin. Consistent with the concept that the glycosphingolipids support slow rolling and the transition to firm arrest, inhibiting UDP-Glucose Ceramide Glucosyltransferase activity resulted in frequent leukocyte detachment events, skipping motion, and reduced diapedesis across the endothelium. Cells bearing truncated O- and N-glycans also sustained cell rolling on E-selectin, although their ability to be recruited from free fluid flow was diminished. CONCLUSIONS: Glycosphingolipids likely contribute to human myeloid cell adhesion to E-selectin under fluid shear, particularly the transition of rolling cells to firm arrest. PMID- 26868210 TI - Asthma Associates With Human Abdominal Aortic Aneurysm and Rupture. AB - OBJECTIVE: Both asthma and abdominal aortic aneurysms (AAA) involve inflammation. It remains unknown whether these diseases interact. APPROACH AND RESULTS: Databases analyzed included Danish National Registry of Patients, a population based nationwide case-control study included all patients with ruptured AAA and age- and sex-matched AAA controls without rupture in Denmark from 1996 to 2012; Viborg vascular trial, subgroup study of participants from the population-based randomized Viborg vascular screening trial. Patients with asthma were categorized by hospital diagnosis, bronchodilator use, and the recorded use of other anti asthma prescription medications. Logistic regression models were fitted to determine whether asthma associated with the risk of ruptured AAA in Danish National Registry of Patients and an independent risk of having an AAA at screening in the Viborg vascular trial. From the Danish National Registry of Patients study, asthma diagnosed <1 year or 6 months before the index date increased the risk of AAA rupture before (odds ratio [OR]=1.60-2.12) and after (OR=1.51-2.06) adjusting for AAA comorbidities. Use of bronchodilators elevated the risk of AAA rupture from ever use to within 90 days from the index date, before (OR=1.10-1.37) and after (OR=1.10-1.31) adjustment. Patients prescribed anti-asthma drugs also showed an increased risk of rupture before (OR=1.12-1.79) and after (OR=1.09-1.48) the same adjustment. In Viborg vascular trial, anti asthmatic medication use associated with increased risk of AAA before (OR=1.45) or after adjustment for smoking (OR=1.45) or other risk factors (OR=1.46). CONCLUSIONS: Recent active asthma increased risk of AAA and ruptured AAA. These findings document and furnish novel links between airway disease and AAA, 2 common diseases that share inflammatory aspects. PMID- 26868213 TI - Fish innate immunity against intestinal helminths. AB - Most individual fish in farmed and wild populations are infected with parasites. Upon dissection of fish, helminths from gut are often easily visible. Enteric helminths include several species of digeneans, cestodes, acanthocephalans and nematodes. Some insights into biology, morphology and histopathological effects of the main fish enteric helminths taxa will be described here. The immune system of fish, as that of other vertebrates, can be subdivided into specific and aspecific types, which in vivo act in concert with each other and indeed are interdependent in many ways. Beyond the small number of well-described models that exist, research focusing on innate immunity in fish against parasitic infections is lacking. Enteric helminths frequently cause inflammation of the digestive tract, resulting in a series of chemical and morphological changes in the affected tissues and inducing leukocyte migration to the site of infection. This review provides an overview on the aspecific defence mechanisms of fish intestine against helminths. Emphasis will be placed on the immune cellular response involving mast cells, neutrophils, macrophages, rodlet cells and mucous cells against enteric helminths. Given the relative importance of innate immunity in fish, and the magnitude of economic loss in aquaculture as a consequence of disease, this area deserves considerable attention and support. PMID- 26868211 TI - Profound Actions of an Agonist of Growth Hormone-Releasing Hormone on Angiogenic Therapy by Mesenchymal Stem Cells. AB - OBJECTIVE: The efficiency of cell therapy is limited by poor cell survival and engraftment. Here, we studied the effect of the growth hormone-releasing hormone agonist, JI-34, on mesenchymal stem cell (MSC) survival and angiogenic therapy in a mouse model of critical limb ischemia. APPROACH AND RESULTS: Mouse bone marrow derived MSCs were incubated with or without 10(-8) mol/L JI-34 for 24 hours. MSCs were then exposed to hypoxia and serum deprivation to detect the effect of preconditioning on cell apoptosis, migration, and tube formation. For in vivo tests, critical limb ischemia was induced by femoral artery ligation. After surgery, mice received 50 MUL phosphate-buffered saline or with 1*10(6) MSCs or with 1*10(6) JI-34-reconditioned MSCs. Treatment of MSCs with JI-34 improved MSC viability and mobility and markedly enhanced their capability to promote endothelial tube formation in vitro. These effects were paralleled by an increased phosphorylation and nuclear translocation of signal transducer and activator of transcription 3. In vivo, JI-34 pretreatment enhanced the engraftment of MSCs into ischemic hindlimb muscles and augmented reperfusion and limb salvage compared with untreated MSCs. Significantly more vasculature and proliferating CD31(+) and CD34(+) cells were detected in ischemic muscles that received MSCs treated with JI-34. CONCLUSIONS: Our studies demonstrate a novel role for JI-34 to markedly improve therapeutic angiogenesis in hindlimb ischemia by increasing the viability and mobility of MSCs. These findings support additional studies to explore the full potential of growth hormone-releasing hormone agonists to augment cell therapy in the management of ischemia. PMID- 26868212 TI - Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina. AB - OBJECTIVE: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. APPROACH AND RESULTS: Hs cTnT and NT-proBNP were measured in 378 patients (60.1+/-0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2 132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). CONCLUSIONS: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP. PMID- 26868214 TI - Molecular and immune response characterizations of IL-6 in large yellow croaker (Larimichthys crocea). AB - Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine which exists in multiple tissues and cell lines. In the present study, the full-length cDNA and the genomic sequence of IL-6 (LcIL-6) were cloned from large yellow croaker, Larimichthys crocea. The full-length cDNA of LcIL-6 was 1066 base pairs (bp), containing an open reading frame (ORF) of 678 bp encoding for 225 amino acids, a 5' untranslated region (UTR) of 71 bp and a 3' UTR of 317 bp. The predicted LcIL 6 protein included a 24 amino acids (aa) signal peptide and a conserved IL-6 domain. However, the polypeptide sequence identities between LcIL-6 and its counterparts in mammals and other fish are from 12% to 45%. The genome sequence of LcIL-6 gene was composed of 2126 bp, including five exons and four introns. Phylogenetic analysis revealed that LcIL-6 showed a close relationship with the IL-6 from other bony fish. Quantitative real-time PCR (qRT-PCR) analysis revealed that LcIL-6 mRNA was expressed in most examined tissues, with the most predominant expression in stomach, followed by blood and very weak expression in other tissues. The expression levels of LcIL-6 after challenged with LPS, poly I:C and Vibrio parahaemolyticus were investigated in spleen, head-kidney and liver. LcIL-6 transcripts were induced significantly after immune challenge, with the peak-value of 33.5 times as much as the control in the head-kidney at 3 h after LPS injection (p < 0.05). Overexpression of LcIL-6 enhanced tumor necrosis factor (TNF)-alpha transcripts significantly (p < 0.05) in L. crocea kidney (LCK) cells. Additionally, recombinant LcIL-6 mature peptide was obtained in the supernatant of Escherichia coli BL21 (DE3). The purified recombinant LcIL-6 fusion protein was also demonstrated to improve the transcriptional expression levels of TNF-alpha significantly in LCK cells (p < 0.05). However, no significant changes of Mx (myxovirus resistant protein), IL-1beta, janus kinase (JAK)2, signal transducers and activators of transcription (STAT)3 and STAT5 in LCK cells was detected after LcIL-6 overexpression or recombinant LcIL-6 protein stimulation. Our results indicated that LcIL-6 might be important in large yellow croaker immune response and improve the inflammatory response by through activation TNF-alpha expression. PMID- 26868215 TI - How to remove the retroauricular driveline in the Jarvik 2000 after heart transplantation. AB - The Jarvik 2000 is a left ventricular assist device (LVAD) used as either a bridge-to-transplant or destination therapy with the possibility of retroauricular percutaneous power delivery (pedestal). Percutaneous driveline infection in LVAD is a life-threatening complication that affects both the quality and length of life in patients. With its rigid fixation to the bone, the pedestal and the vascularity of scalp skin promote healing and reduce the risk of driveline infection. We describe a technique to remove the skull-mounted percutaneous pedestal of the Jarvik 2000 after heart transplantation. PMID- 26868216 TI - Comparison of nafamostat mesilate and unfractionated heparin as anticoagulants during continuous renal replacement therapy. AB - PURPOSE: Nafamostat mesilate (NM) can be used as a regional anticoagulant for continuous renal replacement therapy (CRRT). The primary aim of this study was to assess the association of the use of NM with risk of bleeding complications and compare it with the use of unfractionated heparin (UFH). METHODS: We conducted a single-center retrospective observational study. We included adult patients who required CRRT in our intensive care unit from 2011 to 2013. The primary outcome was the risk of bleeding complications during CRRT and the secondary outcome was filter life for the first filter of CRRT. RESULTS: We included 101 patients (76 with NM, 25 with UFH). Among the 101 patients, use of NM tended to be associated with lower risk of bleeding complications (6.6% vs. 16%; odds ratio, 0.37; p = 0.16). Propensity score matching generated 30 patients with NM and 15 patients with UFH with well-balanced baseline characteristics. Among the propensity score matched cohorts, use of NM was significantly associated with decreased risk of bleeding complications (3.3% vs. 27%; odds ratio, 0.09; p = 0.04). In multivariate logistic analysis using the inverse probability of treatment weighting for sensitive analysis, the use of NM was independently associated with reduced risk of bleeding complications (p = 0.02). The median filter life was not significantly different for patients with NM and patients with UFH (25.5 hours vs. 30.5 hours, p = 0.16). CONCLUSIONS: In our retrospective analysis, the use of NM as an anticoagulant during CRRT was associated with decreased incidence of bleeding complications compared with the use of UFH. PMID- 26868217 TI - Morphometric analysis of the infraorbital foramen, canal and groove using cone beam CT: considerations for creating artificial organs. AB - PURPOSE: The aim of this study was to examine the anatomy and variations of the infraorbital foramen and its surroundings via morphometric measurements using cone beam computed tomography (CBCT) scans derived from a 3D volumetric rendering program. METHODS: 354 sides of CBCT scans from 177 patients were examined in this study. DICOM data from these images were exported to Maxilim(r) software in order to generate 3D surface models. The morphometric measurements were done for infraorbital foramen (IOF), infraorbital groove (IOG) and infraorbital canal (IOC). All images were evaluated by 1 radiologist. To assess intra-observer reliability, the Wilcoxon matched-pairs signed rank test was used. Differences between sex, side, age and measurements were evaluated using chi-square and paired t-test and measurements were evaluated using 1-way ANOVA tests. Differences were considered significant when p<0.05. RESULTS: The most common shape was oval for IOF and parallel for IOC without any accessory foramen. The results showed that females have smaller dimensions for the measurements between the two foramen rotundum (FR), FR-IOF, sella-FR, center of the IOF (cIOF)-nasion (N), cIOF-NB (nasion-B) (p>0.05). No significant difference was found according to age groups (p>0.05). CONCLUSIONS: These results provide detailed knowledge of the anatomical characteristics in this particular area. CBCT imaging with lower radiation dose and thin slices can be a powerful tool for anesthesia procedures like infra orbital nerve blocks, for surgical approaches like osteotomies and neurectomies and also for generating artificial prostheses. PMID- 26868220 TI - Ornithinicoccus halotolerans sp. nov., and emended description of the genus Ornithinicoccus. AB - A halotolerant actinobacterial strain, designated EGI 80423T, was isolated from a desert soil of Xinjiang, north-west China, and subjected to a polyphasic taxonomic characterization. Strain EGI 80423T grew at pH 7.0-10.0 and with 0 14.0% (w/v) NaCl, optimally at pH 8.0-9.0 and with 2.0-4.0% (w/v) NaCl. Cells of strain EGI 80423T were Gram-stain-positive, non-motile cocci with diameters of 0.6-0.8 MUm. The diagnostic diamino acid of the peptidoglycan was ornithine, and the interpeptide bridge was Orn <- Glu. The major fatty acids identified were iso C17:1omega9c, iso-C15:0 and iso-C17:0. The predominant menaquinone was MK-8(H4), while the polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unknown phospholipids, two unknown glycolipids, six unknown phosphoglycolipids and five unknown polar lipids. The G+C content of the genomic DNA was 72.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain EGI 80423T clustered with the single member of the genus Ornithinicoccus. Sequence similarity between strain EGI 80423T and Ornithinicoccus hortensis NBRC 16434T. Because the type strain has been provided by NBRC, Japan was 97.7%. The DNA-DNA relatedness value between strain EGI 80423T and O. hortensis NBRC 16434T was 36.84%. Based on morphological, chemotaxonomic and phylogenetic characteristics, and DNA-DNA hybridization data, strain EGI 80423T represents a novel species of the genus Ornithinicoccus, for which the name Ornithinicoccus halotolerans sp. nov. is proposed. The type strain is EGI 80423T (=CGMCC 1.14989T=KCTC 39700T). The description of the genus Ornithinicoccus has also been emended. PMID- 26868221 TI - AdapterRemoval v2: rapid adapter trimming, identification, and read merging. AB - BACKGROUND: As high-throughput sequencing platforms produce longer and longer reads, sequences generated from short inserts, such as those obtained from fossil and degraded material, are increasingly expected to contain adapter sequences. Efficient adapter trimming algorithms are also needed to process the growing amount of data generated per sequencing run. FINDINGS: We introduce AdapterRemoval v2, a major revision of AdapterRemoval v1, which introduces (i) striking improvements in throughput, through the use of single instruction, multiple data (SIMD; SSE1 and SSE2) instructions and multi-threading support, (ii) the ability to handle datasets containing reads or read-pairs with different adapters or adapter pairs, (iii) simultaneous demultiplexing and adapter trimming, (iv) the ability to reconstruct adapter sequences from paired-end reads for poorly documented data sets, and (v) native gzip and bzip2 support. CONCLUSIONS: We show that AdapterRemoval v2 compares favorably with existing tools, while offering superior throughput to most alternatives examined here, both for single and multi-threaded operations. PMID- 26868222 TI - Prevalence, Detection and Correlates of PTSD in the Primary Care Setting: A Systematic Review. AB - Research suggests that posttraumatic stress disorder (PTSD) is common, debilitating and frequently associated with comorbid health conditions, including poor functioning, and increased health care utilization. This article systematically reviewed the empirical literature on PTSD in primary care settings, focusing on prevalence, detection and correlates. Twenty-seven studies were identified for inclusion. Current PTSD prevalence in primary care patients ranged widely between 2 % to 39 %, with significant heterogeneity in estimates explained by samples with different levels of trauma exposure. Six studies found detection of PTSD by primary care physicians (PCPs) ranged from 0 % to 52 %. Studies examining associations between PTSD and sociodemographic variables yielded equivocal results. High comorbidity was reported between PTSD and other psychiatric disorders including depression and anxiety, and PTSD was associated with functional impairment or disability. Exposure to multiple types of trauma also raised the risk of PTSD. While some studies indicated that primary care patients with PTSD report higher levels of substance and alcohol abuse, somatic symptoms, pain, health complaints, and healthcare utilization, other studies did not find these associations. This review proposes that primary care settings are important for the early detection of PTSD, which can be improved through indicated screening and PCP education. PMID- 26868223 TI - Psychologists in Academic Health Centers and Medical Centers: Being Visible, Relevant and Integral. AB - Psychologists play key roles in academic health centers. This article is an outgrowth of a presentation at the 2015 Conference of the Association of Psychologists in Academic Health Centers addressing various strategies by which psychologists can effectively adapt to and develop successful careers in medical schools, academic health centers, and teaching hospitals. The authors encourage early career and mid-career psychologists in academic health centers to be active, engaged members of their institutions and to participate in multiple aspects of the research, educational, and clinical missions. PMID- 26868224 TI - Biscuspid aortic valve syndrome: diversity and controversy. PMID- 26868226 TI - Evaluation of Clinical Outcomes of Osseointegrated Dental Implantation of Fibula Free Flaps for Mandibular Reconstruction. AB - IMPORTANCE: Dental implantation has been used for oral rehabilitation to improve cosmesis and function. OBJECTIVE: We aim to evaluate the clinical outcomes and success rates of primary and secondary dental implant placement in vascularized fibula bone grafts used for segmental mandibulectomy defects. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed between November 2005 and July 2014 on all patients undergoing both fibula free tissue reconstruction of mandibular defects and endosseous dental implantation at an academic tertiary care referral hospital. INTERVENTIONS: Either primary (n = 20) or secondary (n = 26) dental implantation of the fibula was performed. MAIN OUTCOMES AND MEASURES: Timing of implantation, location of implants, history of tobacco, alcohol, and radiation, reason for mandibulectomy, and outcomes related to these parameters. RESULTS: Forty-six patients (31 males, 15 females; mean age, 58.0 years) underwent dental implantation to the fibula graft. A total of 227 implants were placed, with a mean of 5 implants per patient (range, 2-7). Of these, 44 were placed into native mandible and 183 into fibula flap. Twenty patients underwent primary implantation and received 96 implants, while 26 patients underwent secondary implantation and received 131 implants. There were no flap failures and 22 implant-related complications in 16 patients (implant failure, n = 10; granulation or soft-tissue overgrowth, n = 6; exposed bone around implant, n = 6). An implant failure occurred in 10 patients (22%) resulting in removal of 15 implants. Nine of these patients underwent successful dental rehabilitation, 5 without further implantation, and 4 with replaced implants. One patient was not rehabilitated secondary to failed implantation. Therefore, there was a 93% overall implant survival rate (n = 212) and 98% overall implant-supported prosthesis success rate (n = 45) at a mean follow-up of 22 months. There was no difference in implant survival between primary (94%) (n = 90) and secondary (93%) (n = 122) implantation. Neither a history of preimplant or postimplant radiation exposure nor the diagnosis of osteoradionecrosis affected implant survival. CONCLUSIONS AND RELEVANCE: Osseointegrated dental implantation is a relatively safe procedure with few complications. Vascularized fibula grafts are a suitable method of mandibular reconstruction and are amenable to successful primary and secondary endosseous implantation. LEVEL OF EVIDENCE: 4. PMID- 26868228 TI - New president for BVA's Northern Ireland Branch. PMID- 26868227 TI - BVA President highlights vets' role in protecting animal welfare. PMID- 26868229 TI - Call for a ban on primates as pets. PMID- 26868230 TI - Preferred provider concept 'erodes freedom of choice'. PMID- 26868231 TI - APHA models effects of suspending badger vaccination in Wales. PMID- 26868232 TI - Neglected tropical diseases attract attention in the Lords. PMID- 26868233 TI - New presidents elected. PMID- 26868234 TI - Prince highlights the importance of smallholders and women in farming. PMID- 26868235 TI - Developments in charity and shelter medicine. AB - Topics discussed at a recent meeting of the Association of Charity Vets demonstrated the breadth of charity and shelter medicine, as Georgina Mills reports. PMID- 26868236 TI - Tackling stigma around mental health. PMID- 26868237 TI - New app to help with job searches. PMID- 26868238 TI - Working together to safeguard animal health. AB - Nigel Gibbens, the UK's Chief Veterinary Officer, gives an update on some of the areas of animal health and welfare of particular interest to government and considers how farmers, vets and government can work together to control and respond to animal disease. PMID- 26868239 TI - Northern Ireland disease surveillance report, October to December 2015. AB - .Pneumonia and encephalitis due to Histophilus somni in heifers .Pneumonia due to Bibersteinia trehalosi in a cow .Fasciolosis in ewes and lambs .Dosing gun injuries in lambs .Histomonosis in chickens These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for October to December 2015. PMID- 26868240 TI - Controlling scrapie and bovine spongiform encephalopathy in goats. PMID- 26868241 TI - Hantavirus (Seoul virus) in pet rats: a zoonotic viral threat. PMID- 26868242 TI - Babesiosis in dogs. PMID- 26868243 TI - Stick injuries in dogs. PMID- 26868244 TI - Thermography and saddle fitting. PMID- 26868245 TI - Correction. PMID- 26868246 TI - Collecting the evidence for EBVM. PMID- 26868247 TI - Routine antibiotic dry cow therapy. PMID- 26868254 TI - Challenges of a PhD. AB - While Myfanwy Hill's PhD studies pose an 'enjoyable challenge', she has found that learning to manage her time and studies requires a new level of self discipline. PMID- 26868255 TI - Second-year student diary. PMID- 26868256 TI - Evaluation of Lactobacillus plantarum and Saccharomyces cerevisiae in the Presence of Bifenthrin. AB - This work describes the effect of insecticide bifenthrin on Lactobacillus plantarum and Saccharomyces cerevisiae. Growths of used microorganisms in growth media supplemented with pesticide were studied. Determination of bacterial and yeast fermentation efficiency in wheat supplemented with bifenthrin was conducted. Additionally, investigation of bifenthrin dissipation during microbiological activity was performed. Experiments applying bifenthrin in different concentrations highlighted a negligible impact of the pesticide on the growth of L. plantarum and S. cerevisiae. This insecticide overall negatively affected the yeast fermentation of wheat, while its presence in wheat had a slight negative impact on lactic acid fermentation. The results of bifenthrin dissipation during lactic acid and yeast fermentations of wheat showed that activities of L. plantarum and S. cerevisiae caused lower pesticide reductions. Average bifenthrin residue reduction within samples fermented with L. plantarum was 5.4 % (maximum ~16 %), while within samples fermented with S. cerevisiae, it was 11.6 % (maximum ~17 %). PMID- 26868257 TI - Change in Photosystem II Photochemistry During Algal Growth Phases of Chlorella vulgaris and Scenedesmus obliquus. AB - Sensitivity of photosynthetic processes towards environmental stress is used as a bioanalytical tool to evaluate the responses of aquatic plants to a changing environment. In this paper, change of biomass density, chlorophyll a fluorescence and photosynthetic parameters during growth phases of two microalgae Chlorella vulgaris and Scenedesmus obliquus were studied. The photosynthetic growth behaviour changed significantly with cell age and algae species. During the exponential phase of growth, the photosynthesis capacity reached its maximum and decreased in ageing algal culture during stationary phase. In conclusion, the chlorophyll a fluorescence OJIP method and the derived fluorescence parameters would be an accurate method for obtaining information on maximum photosynthetic capacities and monitoring algal cell growth. This will contribute to more understanding, for example, of toxic actions of pollutants in microalgae test. PMID- 26868258 TI - Aeromonas lusitana sp. nov., Isolated from Untreated Water and Vegetables. AB - During previous studies to evaluate the phylogenetic diversity of Aeromonas from untreated waters and vegetables intended for human consumption, a group of isolates formed a unique gyrB phylogenetic cluster, separated from those of all other species described so far. A subsequent extensive phenotypic characterization, DNA-DNA hybridization, 16S rRNA gene sequencing, multi-locus phylogenetic analysis of the concatenated sequence of seven housekeeping genes (gyrB, rpoD, recA, dnaJ, gyrA, dnaX, and atpD; 4705 bp), and ERIC-PCR, were performed in an attempt to ascertain the taxonomy position of these isolates. This polyphasic approach confirmed that they belonged to a novel species of the genus Aeromonas, for which the name Aeromonas lusitana sp. nov. is proposed, with strain A.11/6(T) (=DSMZ 24095(T), =CECT 7828(T)) as the type strain. PMID- 26868259 TI - Discovery of candidate genes for nonsyndromic cleft lip palate through genome wide linkage analysis of large extended families in the Malay population. AB - BACKGROUND: Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population. RESULTS: A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score >= 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1. CONCLUSIONS: We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted. PMID- 26868260 TI - Melanoma associated antigen (MAGE)-A3 promotes cell proliferation and chemotherapeutic drug resistance in gastric cancer. AB - BACKGROUND: Melanoma-associated antigen (MAGE)-A3 is a member of the family of cancer-testis antigens and has been found to be epigenetically regulated and aberrantly expressed in various cancer types. It has also been found that MAGE-A3 expression may correlate with an aggressive clinical course and with chemo resistance. The objectives of this study were to assess the relationship between MAGE-A3 promoter methylation and expression and (1) gastric cancer patient survival and (2) its functional consequences in gastric cancer-derived cells. METHODS: Samples from two independent gastric cancer cohorts (including matched non-malignant gastric samples) were included in this study. MAGE-A3 methylation and mRNA expression levels were determined by methylation-specific PCR (MSP) and quantitative real-time PCR (qPCR), respectively. MAGE-A3 expression was knocked down in MKN1 gastric cancer-derived cells using miRNAs. In addition, in vitro cell proliferation, colony formation, apoptosis, cell cycle, drug treatment, immunohistochemistry and Western blot assays were performed. RESULTS: Clinical analysis of 223 primary patient-derived samples (ntumor = 161, nnormal = 62) showed a significant inverse correlation between MAGE-A3 promoter methylation and expression in the cancer samples (R = -0.63, p = 5.99e-19). A lower MAGE-A3 methylation level was found to be associated with a worse patient survival (HR: 1.5, 95 % CI: 1.02-2.37, p = 0.04). In addition, we found that miRNA-mediated knockdown of MAGE-A3 expression in MKN1 cells caused a reduction in its proliferation and colony forming capacities, respectively. Under stress conditions MAGE-A3 was found to regulate the expression of Bax and p21. MAGE-A3 knock down also led to an increase in Puma and Noxa expression, thus contributing to an enhanced docetaxel sensitivity in the gastric cancer-derived cells. CONCLUSIONS: From our results we conclude that MAGE-A3 expression is regulated epigenetically by promoter methylation, and that its expression contributes to gastric cell proliferation and drug sensitivity. This study underscores the potential implications of MAGE-A3 as a therapeutic target and prognostic marker in gastric cancer patients. PMID- 26868261 TI - Social structure and Escherichia coli sharing in a group-living wild primate, Verreaux's sifaka. AB - BACKGROUND: Epidemiological models often use information on host social contacts to predict the potential impact of infectious diseases on host populations and the efficiency of control measures. It can be difficult, however, to determine whether social contacts are actually meaningful predictors of transmission. We investigated the role of host social structure in the transmission of Escherichia coli in a wild population of primates, Verreaux's sifakas (Propithecus verreauxi). Using multilocus sequence typing (MLST), we compared genetic similarities between E. coli isolates from different individuals and groups to infer transmission pathways. RESULTS: Correlation of social and transmission networks revealed that membership to the same group significantly predicted sharing of E. coli MLST sequence types (ST). Intergroup encounter rate and a measure of space-use sharing provided equally potent explanations for type sharing between social groups when closely related STs were taken into account, whereas animal age, sex and dispersal history had no influence. No antibiotic resistance was found, suggesting low rates of E. coli spillover from humans into this arboreal species. CONCLUSIONS: We show that patterns of E. coli transmission reflect the social structure of this group-living lemur species. We discuss our results in the light of the species' ecology and propose scent-marking, a type of social contact not considered in previous epidemiological studies, as a likely route of transmission between groups. However, further studies are needed to explicitly test this hypothesis and to further elucidate the relative roles of direct contact and environmental transmission in pathogen transfer. PMID- 26868262 TI - Pulsatilla saponin A induces differentiation in acute myeloid leukemia in vitro. AB - OBJECTIVES: To identify whether Pulsatilla saponin A (PsA), an active molecule extracted from Pulsatilla chinensis regel, can induce acute myeloid leukemia (AML) cells differentiate. METHODS: PsA was isolated from P. chinensis, and its effects of differentiation induction on both AML cell lines and the primary leukemia cells were investigated. RESULTS: Compared with the untreated control, PsA induced the differentiation of U937 cells, K562 cells and HL-60 cells, represented as the increased CD15+ cells in a dose- and time-dependent manner in all the three AML cell lines, after PsA treatment. As the same time, the cell morphology of these AML cells was changed correspondingly; the cytoplasm/nuclei ratio was increased, basophilic cytoplasm was decreased, and eccentric nucleus and granules were also observed. Also, the same effects of differentiation induction by PSA were confirmed in the primary leukemia cells. However, the specific MEK/ERK inhibitor U0126 effectively abrogated the differentiation induced by PsA in vitro. CONCLUSIONS: PsA can modify the differentiation activity of AML cells, probably though the MEK/ERK signaling pathway. PMID- 26868263 TI - Post-Fukushima radiation education for public health nursing students: a case study. AB - BACKGROUND: The recent Fukushima Nuclear Power Plant accident was one of more than 200 serious nuclear/radiation incidents (accidents and disasters) that occurred worldwide since 1945. The current Fukushima disaster is in the recovery phase with the decreasing levels of radiation in the environment. However, fears and stigma related to the perceived risk of radiation exposure persist among the general population. INTRODUCTION: To improve on students' preparedness for social and public health challenges after a radiation incidence, radiation education was provided for undergraduate public health nursing students. AIM: This case study reports the development and implementation of the first class of radiation education in public health nursing, as well as students' reflections on their class experience. METHODS: We included a 90-min radiation class in an undergraduate public health nursing course in Tokyo, Japan. Lectures/discussion on technical and environmental aspects provided the minimally essential content for basic radiation knowledge. After class, all the 65 students were invited to freely write their reflections on the class. With their consent, 61 students' anonymous written accounts were qualitatively analysed. RESULTS: Five themes emerged: awareness of ignorance about radiation, problems produced by the mass media, becoming knowledgeable about radiation, public health nurses' role, and trustful and enjoyable lecture. DISCUSSION: The class inspired students to consider social, psychological and relational aspects of knowing and not knowing about radiation and their future professional role. CONCLUSION AND IMPLICATIONS FOR NURSING: Once radiation is taught at school, nursing students will emerge as professionals with the belief that radiation is within their professional purview. Education is key to disaster prevention, preparation, response and recovery. Given the ubiquitous nature of health challenges after a radiation incident, radiation education is indispensable for nursing students worldwide. PMID- 26868264 TI - Chromatic-aberration-corrected diffractive lenses for ultra-broadband focusing. AB - We exploit the inherent dispersion in diffractive optics to demonstrate planar chromatic-aberration-corrected lenses. Specifically, we designed, fabricated and characterized cylindrical diffractive lenses that efficiently focus the entire visible band (450 nm to 700 nm) onto a single line. These devices are essentially pixelated, multi-level microstructures. Experiments confirm an average optical efficiency of 25% for a three-wavelength apochromatic lens whose chromatic focus shift is only 1.3 MUm and 25 MUm in the lateral and axial directions, respectively. Super-achromatic performance over the continuous visible band is also demonstrated with averaged lateral and axial focus shifts of only 1.65 MUm and 73.6 MUm, respectively. These lenses are easy to fabricate using single-step grayscale lithography and can be inexpensively replicated. Furthermore, these devices are thin (<3 MUm), error tolerant, has low aspect ratio (<1:1) and offer polarization-insensitive focusing, all significant advantages compared to alternatives that rely on metasurfaces. Our design methodology offers high design flexibility in numerical aperture and focal length, and is readily extended to 2D. PMID- 26868265 TI - Photochemical water oxidation by cyclometalated iridium(iii) complexes: a mechanistic insight. AB - The proficiency of the cyclometalated iridium complexes [(eta(5)-C5Me5)IrCl(L1)] (1), [(eta(5)-C5Me5)IrCl(L2)] (2) and [(eta(5)-C5Me5)IrCl(L3)] (3) has been examined towards photochemical water oxidation. The involvement of Ir(iv/v) in the catalytic process has been explored via CV, UV/vis, XPS spectroscopic studies and appreciable TON relative to the theoretical value of 1 from GC. PMID- 26868266 TI - Synovial-type giant cell tumors of the axial spine. PMID- 26868267 TI - An extremely rare case of a single isolated pituitary metastasis from hepatocellular carcinoma. PMID- 26868268 TI - First experience with Carbon/PEEK pedicle screws. PMID- 26868269 TI - Prediction Methods in Solar Sunspots Cycles. AB - An understanding of the Ohl's Precursor Method, which is used to predict the upcoming sunspots activity, is presented by employing a simplified movable divided-blocks diagram. Using a new approach, the total number of sunspots in a solar cycle and the maximum averaged monthly sunspots number Rz(max) are both shown to be statistically related to the geomagnetic activity index in the prior solar cycle. The correlation factors are significant and they are respectively found to be 0.91 +/- 0.13 and 0.85 +/- 0.17. The projected result is consistent with the current observation of solar cycle 24 which appears to have attained at least Rz(max) at 78.7 +/- 11.7 in March 2014. Moreover, in a statistical study of the time-delayed solar events, the average time between the peak in the monthly geomagnetic index and the peak in the monthly sunspots numbers in the succeeding ascending phase of the sunspot activity is found to be 57.6 +/- 3.1 months. The statistically determined time-delayed interval confirms earlier observational results by others that the Sun's electromagnetic dipole is moving toward the Sun's Equator during a solar cycle. PMID- 26868271 TI - Lesley Fallowfield: Psycho-oncology supremo. PMID- 26868270 TI - Unintended Effects of a Smoking Cessation Intervention on Latino Fathers' Binge Drinking In Early Postpartum. PMID- 26868272 TI - Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A. AB - Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER) protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion production in cells infected with cell culture-derived HCV. HCV nonstructural 5A (NS5A) protein, which is a critical factor for HCV RNA replication, interacts with the IFN-beta-inducible protein SCOTIN, which transports NS5A to autophagosomes for degradation. Furthermore, the suppressive effect of SCOTIN on HCV replication is impaired in both ATG7-silenced cells and cells treated with autophagy or lysosomal inhibitors. SCOTIN does not affect the overall flow of autophagy; however, it is a substrate for autophagic degradation. The physical association between the transmembrane/proline-rich domain (TMPRD) of SCOTIN and Domain-II of NS5A is essential for autophagosomal trafficking and NS5A degradation. Altogether, our findings suggest that IFN-beta-induced SCOTIN recruits the HCV NS5A protein to autophagosomes for degradation, thereby restricting HCV replication. PMID- 26868275 TI - Determination of (241)Pu by the method of disturbed radioactive equilibrium using 2pialpha-counting and precision gamma-spectrometry. AB - A simple technique is proposed for the determination of the content of (241)Pu, which is based on disturbance of radioactive equilibrium in the genetically related (237)U<-(241)Pu->(241)Am decay chain of radionuclides, with the subsequent use of 2pialpha-counting and precision gamma-spectroscopy for monitoring the process of restoration of that equilibrium. It has been shown that the data on dynamics of accumulation of the daughter (241)Am, which were obtained from the results of measurements of alpha- and gamma-spectra of the samples, correspond to the estimates calculated for the chain of two genetically related radionuclides, the differences in the estimates of (241)Pu radioactivity not exceeding 2%. Combining the different methods of registration (2pialpha-counting, semiconductor alpha- and gamma-spectrometry) enables the proposed method to be efficiently applied both for calibration of (241)Pu-sources (from several hundreds of kBq and higher) and for radioisotopic analysis of plutonium mixtures. In doing so, there is a deep purification of (241)Pu from its daughter decay products required due to unavailability of commercial detectors that could make it possible, based only on analysis of alpha-spectra, to conduct quantitative analysis of the content of (238)Pu and (241)Am. PMID- 26868274 TI - An improved combustion apparatus for the determination of organically bound tritium in environmental samples. AB - This paper reports an improved combustion apparatus for the determination of organically bound tritium in environmental samples. The performance of this apparatus including the recovery rate and reproducibility was investigated by combusting lettuce and pork samples. To determine the factors for the different recovery rates of lettuce and pork and investigate whether the samples were completely oxidized, the ashes and exhaust gases produced by the combustion were analyzed. The results indicate that the apparatus showed an excellent performance in the combustion of environmental samples. Thus, the improvements conducted in this study were effective. PMID- 26868273 TI - Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival. AB - BACKGROUND: Ovarian tissue preservation is proposed to patients at risk of premature ovarian failure, but this procedure still needs to be optimized. To limit injury during ovarian tissue cryopreservation, anti-apoptotic drugs were added to the transport and freezing media of ovarian cortex tissue. METHODS: Sheep ovaries were transported, prepared and frozen in solutions containing vehicle or anti-apoptotic drugs (Z-VAD-FMK, a pan-caspase inhibitor, or sphingosine-1-phosphate (S1P), a bioactive lipid). After the tissue was thawed, the ovarian cortex was cultured for 2 or 6 days. Follicular quantification and morphological and proliferation analyses were performed on histological sections. RESULTS: After 2 days of culture, S1P improved the quality of primordial follicles; higher densities of morphologically normal and proliferative primordial follicles were found. Z-VAD-FMK displayed similar effects by preserving global primordial follicular density, but this effect was evident after 6 days of culture. This drug also improved cell proliferation after 2 and 6 days of culture. CONCLUSIONS: Our results showed that the addition of S1P or Z VAD-FMK to the transport and freezing media prior to ovarian tissue cryopreservation improves primordial follicular quality and therefore improves global tissue survival. This should ultimately lead to improved fertility restoration after auto-transplantation. PMID- 26868276 TI - Cognitive Behaviour Therapy for Post-Traumatic Stress Disorder in a person with an Autism Spectrum Condition and Intellectual Disability: A Case Study. AB - BACKGROUND: One of the difficulties in assessing and treating PTSD in people with intellectual disability is that it may not present with the typical symptoms associated with the disorder. This may be why there is a dearth of literature on the treatment of PTSD using cognitive behavioural approaches for people with intellectual disability (e.g. Ehlers et al. Behav Res Ther, 43, 2005, 413-431). This paper reports the treatment for PTSD in a young man diagnosed with autism and a mild intellectual disability. METHOD: Treatment involved 12 sessions of cognitive therapy for PTSD using the approach developed by Ehlers et al. RESULTS: There was an overall reduction in symptoms and a self-reported elevation in mood. With careful questioning, adaptation of language and elucidation of concepts, the patient was able to fully engage in therapy. DISCUSSION: This case suggests that cognitive approaches to treating PTSD can be successful in people with intellectual disability and autism. PMID- 26868277 TI - Various clinical conditions can mimic Crimean-Congo hemorrhagic fever in pediatric patients in endemic regions. AB - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9%) CCHF; 7 patients had (33.3%) viral upper respiratory tract infections (URTI); 2 patients had (9.5%) brucellosis; 1 patients had (4.7%) periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome episode; 1 patient had (4.7%) cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7%) cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1+/-53.6 vs. 94.1+/-52.1 months, p=0.02). Seventeen (81%) of the children included had a history of tick bites, 2 (9.5%) had a history of contact with a patient with CCHF, and 2 (9.5%) had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56+/ 1.42 vs. 6.75+/-3.62 days, p=0.008) and a longer mean length of hospitalization (8.00+/-2.08 vs. 3.58+/-1.56 days, p<0.001) than the other patients. At laboratory examination, patients with CCHF had statistically significant lower leukocyte and platelet counts, more prolonged coagulation parameters, and greater AST, ALT, LDH, and CK levels than the other patients. No mortality or complications occurred in the study. Both infectious causes, such as URTI, cellulitis, and brucellosis, and non-infectious causes may resemble CCHF. Although they are not pathognomonic, some indicators, including a longer symptom duration and hospitalization, cytopenia, elevated liver enzymes, creatine kinase and prolonged coagulation parameters, were found to be in favor of CCHF. PMID- 26868278 TI - High-flow oxygen therapy in cluster headache patients has no significant effect on nociception specific blink reflex parameters: a pilot study. AB - BACKGROUND: The exact pathophysiology of cluster headache is unclear. We examined the influence of interneurons on the trigemino-facial reflex arch and the effect of oxygen, by using the nociception specific blink reflex parameters. FINDINGS: There is no significant effect of oxygen, immediately and over time, on the nociception specific blink reflex parameters in ten male patients during the active phase of cluster headache, outside attacks. Also, there is no significant difference between the symptomatic and asymptomatic side. None of the subjects experienced a cluster headache attack during study participation. We therefore present the collected data as reference values of nociception specific trigeminal stimulation and the effect of oxygen on nociception specific blink reflex parameters. CONCLUSION: The nociception specific blink reflex seems not a suitable instrument for exploring the pathophysiology of cluster headache. PMID- 26868279 TI - Is the Care Transitions Measure Associated with Readmission Risk? Analysis from a Single Academic Center. AB - BACKGROUND: It is widely hypothesized that improvement in transitions of care will reduce unplanned hospital readmissions. However, the association between the Care Transitions Measure, the national quality metric for transitions of care and readmission risk, has not been established. OBJECTIVE: We aimed to determine the association between the Care Transition Measure and readmission. DESIGN: This was a single-center, prospective cohort study. PARTICIPANTS: Convenience sample of 2,963 patients enrolled in the "Bridging the Divides" program, a longitudinal care management program for patients with coronary revascularization, from 2013 to 2014. Of these, 1594 (54 %) patients completed a post-discharge Care Transition Measure questionnaire. INTERVENTION: Care Transition Measure scores were collected by trained research staff blinded to study hypothesis, by telephone, within 30 days of discharge. Higher Care Transition Measure scores reflect a higher quality transition of care. MAIN MEASURES: 30-day readmission was measured. KEY RESULTS: Of the1594 patients that completed the Care Transition Measure survey, 1216 (76 %) received percutaneous coronary intervention and 378 (24 %) received coronary artery bypass grafting. Mean Care Transition Measure scores were significantly lower among patients who had a prior admission (77.2 vs. 82.1, p < 0.001) and those with >= 5 comorbidities (77 vs. 82.6 vs. 81.6, p < 0.001). Mean scores were significantly lower among patients who were readmitted within the percutaneous coronary intervention subgroup (73 vs. 80.9, p < 0.001) and the total study population (74.6 vs. 81.1, p < 0.001) compared to those who were not readmitted. This was not the case in the coronary artery bypass grafting subgroup (78.5 vs. 81.7, p = 0.29). After multivariable adjustment, every ten point increase in the Care Transition Measure score was associated with a 14 % reduction in readmission risk (adjusted odds ratio 0.86, 95 % CI 0.78-0.95). CONCLUSIONS: The Care Transition Measure is strongly associated with readmissions, which strengthens its validity. However, its association with patient variables linked with readmission and its inconsistent association with readmission across clinical groups raises concerns that scores may be influenced by patient characteristics. PMID- 26868280 TI - Codelivery of DNA vaccination encoding LeIF gene and IL-12 increases protection against Leishmania major infection in BALB/c mice. AB - Previous studies have shown that Leishmania elongation initiation factor (LeIF) antigen causes a partial immunity against leishmaniasis. The antigen develops type I immunity by overexpression of inflammatory cytokines such as interleukin 12 (IL-12), IFN-gamma and TNF-alpha. Therefore, We evaluated immune responses induced by the LeIF gene against Leishmania major infection. Immunization with LeIF gene alone or with IL-12 induced Th1 response and produced higher IFN-gamma and lower IL-4 levels by splenocytes than control groups (P < 0.05) and also ratios of IFN-gamma/IL-4 were 11.68 to 18.53 times more in immunized groups than control groups after challenge. In addition, analysis of humoral immune response revealed that immunized mice had more IgG2a levels than both control groups (P < 0.05). On the other hand, lesion size was less for immunized animals than control groups from 4th week after challenge (P < 0.05). The percentage reduction in lesion size was 29.30% for LeIF and 51.98% for LeIF + IL-12 than PBS at 12th week post-infection. Spleen parasite burden decreased in all immunized groups in comparison with control groups (P < 0.05). The results indicated that LeIF gene induced partial immunity against L. major infection in BALB/c mice. However, LeIF plus IL-12 group showed more potent immunity with smaller lesions than other groups. PMID- 26868282 TI - GMOL: An Interactive Tool for 3D Genome Structure Visualization. AB - It has been shown that genome spatial structures largely affect both genome activity and DNA function. Knowing this, many researchers are currently attempting to accurately model genome structures. Despite these increased efforts there still exists a shortage of tools dedicated to visualizing the genome. Creating a tool that can accurately visualize the genome can aid researchers by highlighting structural relationships that may not be obvious when examining the sequence information alone. Here we present a desktop application, known as GMOL, designed to effectively visualize genome structures so that researchers may better analyze genomic data. GMOL was developed based upon our multi-scale approach that allows a user to scale between six separate levels within the genome. With GMOL, a user can choose any unit at any scale and scale it up or down to visualize its structure and retrieve corresponding genome sequences. Users can also interactively manipulate and measure the whole genome structure and extract static images and machine-readable data files in PDB format from the multi-scale structure. By using GMOL researchers will be able to better understand and analyze genome structure models and the impact their structural relations have on genome activity and DNA function. PMID- 26868281 TI - Overfeeding during a critical postnatal period exacerbates hypothalamic-pituitary adrenal axis responses to immune challenge: a role for adrenal melanocortin 2 receptors. AB - Early life diet can critically program hypothalamic-pituitary-adrenal (HPA) axis function. We have previously shown rats that are overfed as neonates have exacerbated pro-inflammatory responses to immune challenge with lipopolysaccharide (LPS), in part by altering HPA axis responses, but how this occurs is unknown. Here we examined neonatal overfeeding-induced changes in gene expression in each step of the HPA axis. We saw no differences in glucocorticoid or mineralocorticoid receptor expression in key regions responsible for glucocorticoid negative feedback to the brain and no differences in expression of key HPA axis regulatory genes in the paraventricular nucleus of the hypothalamus or pituitary. On the other hand, expression of the adrenal melanocortin 2 receptor (MC2R) is elevated after LPS in control rats, but significantly less so in the neonatally overfed. The in vitro adrenal response to ACTH is also dampened in these rats, while the in vivo response to ACTH does not resolve as efficiently as it does in controls. These data suggest neonatal diet affects the efficiency of the adrenally-mediated response to LPS, potentially influencing how neonatally overfed rats combat bacterial infection. PMID- 26868283 TI - Cost Effectiveness of Influenza Vaccine Choices in Children Aged 2-8 Years in the U.S. AB - INTRODUCTION: Prior evidence found live attenuated influenza vaccine (LAIV) more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, leading CDC in 2014 to prefer LAIV use in this group. However, since 2013, LAIV has not proven superior, leading CDC in 2015 to rescind their LAIV preference statement. Here, the cost effectiveness of preferred LAIV use compared with IIV in children aged 2-8 years is estimated. METHODS: A Markov model estimated vaccination strategy cost effectiveness in terms of cost per quality-adjusted life-year gained. Base case assumptions were equal vaccine uptake; IIV use when LAIV was not indicated (in 11.7% of the cohort); and no indirect vaccination effects. Sensitivity analyses included estimates of indirect effects from both equation- and agent-based models. Analyses were performed in 2014-2015. RESULTS: Using prior effectiveness data in children aged 2-8 years (LAIV=83%, IIV=64%), preferred LAIV use was less costly and more effective than IIV (dominant), with results sensitive only to LAIV and IIV effectiveness variation. Using 2014-2015 U.S. effectiveness data (LAIV=0%, IIV=15%), IIV was dominant. In two-way sensitivity analyses, LAIV use was cost saving over the entire range of IIV effectiveness (0%-81%) when absolute LAIV effectiveness was >7.1% higher than IIV, but never cost saving when absolute LAIV effectiveness was <3.5% higher than IIV. CONCLUSIONS: Results support CDC's decision to no longer prefer LAIV use and provide guidance on effectiveness differences between influenza vaccines that might lead to preferential LAIV recommendation for children aged 2-8 years. PMID- 26868284 TI - Extended Self-Help for Smoking Cessation: A Randomized Controlled Trial. AB - INTRODUCTION: Far too few smokers receive recommended interventions at their healthcare visits, highlighting the importance of identifying effective, low-cost smoking interventions that can be readily delivered. Self-help interventions (e.g., written materials) would meet this need, but they have shown low efficacy. The purpose of this RCT was to determine the efficacy of a self-help intervention with increased duration and intensity. DESIGN: Randomized parallel trial design involving enrollment between April 2010 and August 2011 with follow-up data for 24 months. SETTING/PARTICIPANTS: U.S. national sample of daily smokers (N=1,874). INTERVENTION: Participants were randomized to one of three arms of a parallel trial design: Traditional Self-Help (TSH, n=638), Standard Repeated Mailings (SRM, n=614), or Intensive Repeated Mailings (IRM, n=622). TSH received an existing self-help booklet for quitting smoking. SRM received eight different cessation booklets mailed over a 12-month period. IRM received monthly mailings of ten booklets and additional material designed to enhance social support over 18 months. MAIN OUTCOME MEASURES: The primary outcome was 7-day point-prevalence abstinence collected at 6, 12, 18, and 24 months. RESULTS: Data were analyzed between 2013 and 2015. A dose-response effect was found across all four follow-up points. For example, by 24 months, IRM produced the highest abstinence rate (30.0%), followed by SRM (24.4%) and TSH (18.9%). The difference in 24-month abstinence rates between IRM and TSH was 11.0% (95% CI=5.7%, 16.3%). Cost analyses indicated that, compared with TSH, the incremental cost per quitter who received SRM and IRM was $560 and $361, respectively. CONCLUSIONS: Self-help interventions with increased intensity and duration resulted in significantly improved abstinence rates that extended 6 months beyond the end of the intervention. Despite the greater intensity, the interventions were highly cost effective, suggesting that widespread dissemination in healthcare settings could greatly enhance quitting. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01352195. PMID- 26868285 TI - Receipt of Care Discordant with Practice Guidelines is Associated with Compromised Overall Survival in Nasopharyngeal Carcinoma. AB - AIMS: It is unknown whether receiving treatment that is discordant with practice guidelines is associated with improved survival in patients with nasopharyngeal carcinoma. The objectives of this study were to characterise national treatment patterns, analyse whether treatment outside of practice guidelines is associated with overall survival, and identify variables associated with receiving guidelines-discordant care in the USA. MATERIALS AND METHODS: This was a retrospective cohort study of 1741 nasopharyngeal carcinoma patients in the National Cancer Data Base (2003-2006). Treatment regimens were compared with the 2004-2006 National Comprehensive Cancer Network guidelines. Statistical analyses included chi-square, Kaplan-Meier, multivariable logistic, and Cox regression. RESULTS: Nearly 26% of our cohort received care discordant with practice guidelines. In multivariable analysis, patients with stage IVC disease (odds ratio 2.59, 95% confidence interval 1.66-4.04) were more likely to receive guidelines-discordant care when compared with those with stage II-IVB disease. The most common treatment deviation for those with stage I disease was overtreatment with chemoradiation therapy. Receiving guidelines-discordant care was associated with an increased risk of death (hazard ratio 1.46, 95% confidence interval 1.25-1.69). CONCLUSIONS: Many patients with stages I and IVC nasopharyngeal carcinoma do not receive care in accordance with practice guidelines. Receiving guidelines-discordant care is associated with compromised overall survival in the USA. PMID- 26868286 TI - Do Patient-reported Outcome Measures Agree with Clinical and Photographic Assessments of Normal Tissue Effects after Breast Radiotherapy? The Experience of the Standardisation of Breast Radiotherapy (START) Trials in Early Breast Cancer. AB - AIMS: In radiotherapy trials, normal tissue effects (NTE) are important end points and it is pertinent to ask whether patient-reported outcome measures (PROMs) could replace clinical and/or photographic assessments. Data from the Standardisation of Breast Radiotherapy (START) trials are examined. MATERIALS AND METHODS: NTEs in the treated breast were recorded by (i) annual clinical assessments, (ii) photographs at 2 and 5 years, (iii) PROMs at 6 months, 1, 2 and 5 years after radiotherapy. Hazard ratios for the radiotherapy schedules were compared. Measures of agreement of assessments at 2 and 5 years tested concordance. RESULTS: PROMs were available at 2 and/or 5 years for 1939 women, of whom 1870 had clinical and 1444 had photographic assessments. All methods were sensitive to the dose difference between schedules. Patients reported a higher prevalence for all NTE end points than clinicians or photographs (P < 0.001 for most NTEs). Concordance was generally poor; weighted kappa at 2 years ranged from 0.05 (telangiectasia) to 0.21 (shrinkage and oedema). The percentage agreement was lowest between PROMs and photographic assessments of change in breast appearance (38%). CONCLUSIONS: All three methods produced similar conclusions for the comparison of trial schedules, despite low concordance between the methods on an individual patient basis. Careful consideration should be given to the different contributions of the measures of NTE in future radiotherapy trials. PMID- 26868287 TI - Are Organisms Adapting to Ionizing Radiation at Chernobyl? AB - Numerous organisms have shown an ability to survive and reproduce under low-dose ionizing radiation arising from natural background radiation or from nuclear accidents. In a literature review, we found a total of 17 supposed cases of adaptation, mostly based on common garden experiments with organisms only deriving from typically two or three sampling locations. We only found one experimental study showing evidence of improved resistance to radiation. Finally, we examined studies for the presence of hormesis (i.e., superior fitness at low levels of radiation compared with controls and high levels of radiation), but found no evidence to support its existence. We conclude that rigorous experiments based on extensive sampling from multiple sites are required. PMID- 26868289 TI - Adversity, Maltreatment, and Resilience in Young Children. AB - BACKGROUND: Much of the research on children in high risk environments, particularly those who have been maltreated, has focused on negative outcomes. Yet, much can be learned from some of these children who fare relatively well. The objective was to examine resilience in high-risk preschoolers, and to probe contributors to their adaptive functioning. METHODS: The sample of 943 families was from the Longitudinal Studies of Child Abuse and Neglect, a consortium of 5 sites, prospectively examining the antecedents and outcomes of maltreatment. Most of the families were at high risk for maltreatment, and many had been reported to Child Protective Services (CPS) by the time the children were aged 4 years. Standardized measures were used at ages 4 and 6 to assess the children's functioning in behavioral, social and developmental domains, and parental depressive symptoms and demographic characteristics. Maltreatment was determined on the basis of CPS reports. Logistic regressions were conducted to predict resilience, defined as competencies in all 3 domains, over time. RESULTS: Forty eight percent of the sample appeared resilient. This was associated with no history of maltreatment (odds ratio = 1.50; 95% confidence interval [CI], 1.02 2.20; P = .04), a primary caregiver reporting few depressive symptoms (odds ratio = 2.19; 95% CI, 1.63-2.94; P < .001), (P = .014), and fewer children in the home (P = .03). CONCLUSIONS: Almost half of the sample appeared resilient during this important developmental period of transition to school. This enables clinicians to be cautiously optimistic in their work with high-risk children and their families. However, more than half the sample was not faring well. Child maltreatment and caregiver depressive symptoms were strongly associated with poor outcomes. These children and families deserve careful attention by pediatric practitioners and referral for prevention and early intervention services. PMID- 26868288 TI - Edaravone, a potent free radical scavenger and a calcium channel blocker attenuate isoproterenol induced myocardial infarction by suppressing oxidative stress, apoptotic signaling and ultrastructural damage. AB - OBJECTIVES: In the present study, we investigated whether combination therapy of low-dose benidipine with the potent free radical scavenger edaravone has a cardioprotective effect against isoproterenol (ISO)-induced myocardial infarction (MI) in Wistar rats. METHODS: Rats were pretreated with concurrent doses of benidipine and edaravone (1 MUg/kg/day + 1 mg/kg/day and 3 MUg/kg/day + 3 mg/kg/day) by intravenous (i.v.) and intraperitoneal (i.p.) routes respectively for 28 days, followed by MI induction using ISO (85 mg/kg) by subcutaneous route for two days at 24 h intervals. After the treatment period, blood was withdrawn and the heart was preserved for biochemical estimations. RESULTS: The activities of the cardiac biomarkers (lactate dehydrogenase and creatine kinase-MB), and the level of malondialdehyde (MDA) significantly increased, while antioxidant markers (reduced glutathione, catalase, superoxidase dismutase, glutathione peroxidase, glutathione reductase) were significantly decreased in the ISO intoxicated group compared with the control group. Moreover, the level of C-reactive protein (CRP) and Caspase-3 activity significantly increased in ISO-intoxicated group. An ultrastructure study was also carried out. Pretreatment with a combination of benidipine and edaravone significantly attenuated the activities of the cardiac biomarkers and the level of MDA, and significantly increased the antioxidant markers compared with the ISO-intoxicated group. Furthermore, pretreatment with the combination of benidipine and edaravone significantly decreased the level of CRP and Caspase-3 activity as compared to the ISO-treated group. The ultrastructure study of myocardium revealed that pretreated groups preserved the mitochondrial shape, the membrane and its internal structures. CONCLUSION: Taken together these results suggest that the combination of benidipine and edaravone showed significant protective effect in ISO-induced MI. PMID- 26868290 TI - Syntabulin regulates the trafficking of PICK1-containing vesicles in neurons. AB - PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein that interacts with diverse membrane proteins. PICK1 has been shown to regulate the clustering and membrane localization of synaptic receptors such as AMPA (alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, metabotropic glutamate receptor 7, and ASICs (acid-sensing ion channels). Moreover, recent evidence suggests that PICK1 can mediate the trafficking of various vesicles out from the Golgi complex in several cell systems, including neurons. However, how PICK1 affects vesicle-trafficking dynamics remains unexplored. Here, we show that PICK1 mediates vesicle trafficking by interacting with syntabulin, a kinesin binding protein that mediates the trafficking of both synaptic vesicles and mitochondria in axons. Syntabulin recruits PICK1 onto microtubule structures and mediates the trafficking of PICK1-containing vesicles along microtubules. In neurons, syntabulin alters PICK1 expression by recruiting PICK1 into axons and regulates the trafficking dynamics of PICK1-containing vesicles. Furthermore, we show that syntabulin forms a complex with PICK1 and ASICs, regulates ASIC protein expression in neurons, and participates in ASIC-induced acidotoxicity. PMID- 26868291 TI - Structural basis for cellulose binding by the type A carbohydrate-binding module 64 of Spirochaeta thermophila. AB - Spirochaeta thermophila secretes seven glycoside hydrolases for plant biomass degradation that carry a carbohydrate-binding module 64 (CBM64) appended at the C terminus. CBM64 adsorbs to various beta1-4-linked pyranose substrates and shows high affinity for cellulose. We present the first crystal structure of a CBM64 at 1.2 A resolution, which reveals a jelly-roll-like fold corresponding to a surface binding type A CBM. Modeling of its interaction with cellulose indicates that CBM64 achieves association with the hydrophobic face of beta-linked pyranose chains via a unique coplanar arrangement of four exposed tryptophan side chains. Proteins 2016; 84:855-858. (c) 2016 Wiley Periodicals, Inc. PMID- 26868292 TI - The evaluation of dorsogluteal and ventrogluteal injection sites: a cadaver study. AB - AIMS AND OBJECTIVES: The aim of this study is to measure the thickness of the muscles in the dorsogluteal and the ventrogluteal injection sites and to determine which injection site is farther away from the neurovascular structures. BACKGROUND: Although the dorsogluteal region is frequently used for intramuscular injections, the ventrogluteal region is suggested as a more secure injection site due to its distance to the neurovascular structures. However, there are no measurements regarding the distances of these structures. Due to this reason, the distance between these injection sites and the neurovascular structures should be measured. DESIGN: This study is a descriptive study that used cadavers to measure the distance between the injection sites and the neurovascular structures. METHODS: The study was conducted on 29 cadavers fixed with 10% formalin. The needle was advanced until reaching its end point. A 1.5-inch needle was used for the injections in both regions. The gluteal region was dissected. Parameters were measured with a digital vernier calliper. Data Analysis was performed using spss and the Wilcoxon Signed-Rank Test was used to examine differences among measurements from the two injection regions. Data were collected between February and May 2014. RESULTS: Sum of the thickness of the muscles is greater in the dorsogluteal region. The ventrogluteal region is farther than the dorsogluteal region from neurovascular structures. For the ventrogluteal injection administered from the same side, total thickness of the muscle was 22.22 +/- 5 mm, distance to the superior gluteal artery was 13.87 +/- 16 mm and distance to the superior gluteal nerve was 11.82 +/- 14 mm. For the dorsogluteal injection, total thickness of the muscle was 28.35 +/- 7 mm, distance to the superior gluteal artery was 6.83 +/- 9 mm, and distance to the superior gluteal nerve was 5.67 +/- 9 mm. CONCLUSION: Intramuscular injections must be based on an individual clinical assessment of each patient. RELEVANCE TO CLINICAL PRACTICE: The ventrogluteal region is preferred as the first-choice injection site. A needle of recommended length should be used to reach the target muscle. PMID- 26868293 TI - Impact of Common Diabetes Risk Variant in MTNR1B on Sleep, Circadian, and Melatonin Physiology. AB - The risk of type 2 diabetes (T2D) is increased by abnormalities in sleep quantity and quality, circadian alignment, and melatonin regulation. A common genetic variant in a receptor for the circadian-regulated hormone melatonin (MTNR1B) is associated with increased fasting blood glucose and risk of T2D, but whether sleep or circadian disruption mediates this risk is unknown. We aimed to test if MTNR1B diabetes risk variant rs10830963 associates with measures of sleep or circadian physiology in intensive in-laboratory protocols (n = 58-96) or cross sectional studies with sleep quantity and quality and timing measures from self report (n = 4,307-10,332), actigraphy (n = 1,513), or polysomnography (n = 3,021). In the in-laboratory studies, we found a significant association with a substantially longer duration of elevated melatonin levels (41 min) and delayed circadian phase of dim-light melatonin offset (1.37 h), partially mediated through delayed offset of melatonin synthesis. Furthermore, increased T2D risk in MTNR1B risk allele carriers was more pronounced in early risers versus late risers as determined by 7 days of actigraphy. Our results provide the surprising insight that the MTNR1B risk allele influences dynamics of melatonin secretion, generating a novel hypothesis that the MTNR1B risk allele may extend the duration of endogenous melatonin production later into the morning and that early waking may magnify the diabetes risk conferred by the risk allele. PMID- 26868294 TI - Autophagy Is Dispensable for Macrophage-Mediated Lipid Homeostasis in Adipose Tissue. AB - Adipose tissue (AT) macrophages (ATMs) contribute to obesity-induced inflammation and metabolic dysfunction, but also play critical roles in maintaining tissue homeostasis. ATMs catabolize lipid in a lysosomal-dependent manner required for the maintenance of AT; deficiency in lysosomal acid lipase (Lipa), the enzyme required for lysosome lipid catabolism, leads to AT atrophy and severe hepatic steatosis, phenotypes rescued by macrophage-specific expression of Lipa Autophagy delivers cellular products, including lipid droplets, to lysosomes. Given that obesity increases autophagy in AT and contributes to lipid catabolism in other cells, it was proposed that autophagy delivers lipid to lysosomes in ATMs and is required for AT homeostasis. We found that obesity does increase autophagy in ATMs. However, genetic or pharmacological inhibition of autophagy does not alter the lipid balance of ATMs in vitro or in vivo. In contrast to the deficiency of lysosomal lipid hydrolysis, the ablation of autophagy in macrophages does not lead to AT atrophy or alter metabolic phenotypes in lean or obese animals. Although the lysosomal catabolism of lipid is necessary for normal ATM function and AT homeostasis, delivery of lipid to lysosomes is not autophagy dependent and strongly suggests the existence of another lipid delivery pathway critical to lysosome triglyceride hydrolysis in ATMs. PMID- 26868295 TI - Haploinsufficiency of the Insulin Receptor in the Presence of a Splice-Site Mutation in Ppp2r2a Results in a Novel Digenic Mouse Model of Type 2 Diabetes. AB - Insulin resistance in mice typically does not manifest as diabetes due to multiple compensatory mechanisms. Here, we present a novel digenic model of type 2 diabetes in mice heterozygous for a null allele of the insulin receptor and an N-ethyl-N-nitrosourea-induced alternative splice mutation in the regulatory protein phosphatase 2A (PP2A) subunit PPP2R2A. Inheritance of either allele independently results in insulin resistance but not overt diabetes. Doubly heterozygous mice exhibit progressive hyperglycemia, hyperinsulinemia, and impaired glucose tolerance from 12 weeks of age without significant increase in body weight. Alternative splicing of Ppp2r2a decreased PPP2R2A protein levels. This reduction in PPP2R2A containing PP2A phosphatase holoenzyme was associated with decreased serine/threonine protein kinase AKT protein levels. Ultimately, reduced insulin-stimulated phosphorylated AKT levels were observed, a result that was confirmed in Hepa1-6, C2C12, and differentiated 3T3-L1 cells knocked down using Ppp2r2a small interfering RNAs. Altered AKT signaling and expression of gluconeogenic genes in the fed state contributed to an insulin resistance and hyperglycemia phenotype. This model demonstrates how genetic changes with individually small phenotypic effects interact to cause diabetes and how differences in expression of hypomorphic alleles of PPP2R2A and potentially other regulatory proteins have deleterious effects and may therefore be relevant in determining diabetes risk. PMID- 26868296 TI - Prostaglandin I2 Receptor Agonism Preserves beta-Cell Function and Attenuates Albuminuria Through Nephrin-Dependent Mechanisms. AB - Discovery of common pathways that mediate both pancreatic beta-cell function and end-organ function offers the opportunity to develop therapies that modulate glucose homeostasis and separately slow the development of diabetes complications. Here, we investigated the in vitro and in vivo effects of pharmacological agonism of the prostaglandin I2 (IP) receptor in pancreatic beta cells and in glomerular podocytes. The IP receptor agonist MRE-269 increased intracellular 3',5'-cyclic adenosine monophosphate (cAMP), augmented glucose stimulated insulin secretion (GSIS), and increased viability in MIN6 beta-cells. Its prodrug form, selexipag, augmented GSIS and preserved islet beta-cell mass in diabetic mice. Determining that this preservation of beta-cell function is mediated through cAMP/protein kinase A (PKA)/nephrin-dependent pathways, we found that PKA inhibition, nephrin knockdown, or targeted mutation of phosphorylated nephrin tyrosine residues 1176 and 1193 abrogated the actions of MRE-269 in MIN6 cells. Because nephrin is important to glomerular permselectivity, we next set out to determine whether IP receptor agonism similarly affects nephrin phosphorylation in podocytes. Expression of the IP receptor in podocytes was confirmed in cultured cells by immunoblotting and quantitative real-time PCR and in mouse kidneys by immunogold electron microscopy, and its agonism 1) increased cAMP, 2) activated PKA, 3) phosphorylated nephrin, and 4) attenuated albumin transcytosis. Finally, treatment of diabetic endothelial nitric oxide synthase knockout mice with selexipag augmented renal nephrin phosphorylation and attenuated albuminuria development independently of glucose change. Collectively, these observations describe a pharmacological strategy that posttranslationally modifies nephrin and the effects of this strategy in the pancreas and in the kidney. PMID- 26868297 TI - PKCzeta Is Essential for Pancreatic beta-Cell Replication During Insulin Resistance by Regulating mTOR and Cyclin-D2. AB - Adaptive beta-cell replication occurs in response to increased metabolic demand during insulin resistance. The intracellular mediators of this compensatory response are poorly defined and their identification could provide significant targets for beta-cell regeneration therapies. Here we show that glucose and insulin in vitro and insulin resistance in vivo activate protein kinase C zeta (PKCzeta) in pancreatic islets and beta-cells. PKCzeta is required for glucose- and glucokinase activator-induced proliferation of rodent and human beta-cells in vitro. Furthermore, either kinase-dead PKCzeta expression (KD-PKCzeta) or disruption of PKCzeta in mouse beta-cells blocks compensatory beta-cell replication when acute hyperglycemia/hyperinsulinemia is induced. Importantly, KD PKCzeta inhibits insulin resistance-mediated mammalian target of rapamycin (mTOR) activation and cyclin-D2 upregulation independent of Akt activation. In summary, PKCzeta activation is key for early compensatory beta-cell replication in insulin resistance by regulating the downstream signals mTOR and cyclin-D2. This suggests that alterations in PKCzeta expression or activity might contribute to inadequate beta-cell mass expansion and beta-cell failure leading to type 2 diabetes. PMID- 26868299 TI - Field Evaluations of Tracking/Locating Technologies for Prevention of Missing Incidents. AB - BACKGROUND: Persons with dementia are at risk of a missing incident, which is defined as an instance in which a demented person's whereabouts are unknown to the caregiver and the individual is not in an expected location. Since it is critical to determine the missing person's location as quickly as possible, we evaluated whether commercially available tracking technologies can assist in a rapid recovery. METHODS: This study examined 7 commercially available tracking devices: 3 radio frequency (RF) based and 4 global positioning system (GPS) based, employing realistic tracking scenarios. Outcome measures were time to discovery and degree of deviation from a straight intercept course. RESULTS/CONCLUSION: Across all scenarios tested, GPS devices were found to be approximately twice as efficient as the RF devices in locating a "missing person." While the RF devices showed reasonable performance at close proximity, the GPS devices were found to be more appropriate overall for tracking/locating missing persons over unknown and larger distances. PMID- 26868300 TI - Emergency situations in rheumatology with a focus on systemic autoimmune diseases. AB - BACKGROUND AND AIM: Rheumatic diseases are commonly considered chronic conditions. However, acute manifestations can be very severe and represent a diagnostic problem. Examples are systemic lupus erythematosus with acute flare, glomerulonephritis, CNS disorders and catastrophic antiphospholipid syndrome, scleroderma with interstitial lung disease, pulmonary hypertension and renal crisis and polyangiitis with alveolar haemorhage and acute respiratory failure. This aim of this paper is to overview emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides. METHODS: A Pubmed search for both original and review articles, recent textbooks and current guidelines related to rheumatic diseases with possible acute situations were included in this review article. Relevant image documentation was obtained at the site over the past several years of observation. CONCLUSIONS: This paper provides an overview of facts and emergency situations which can be encountered in the care of patients with autoimmune systemic diseases and vasculitides. It is directed at clinicians working in intensive care. It provides a differential diagnostic overview and information which is rare and commonly underestimated. PMID- 26868301 TI - Green emission and Ag(+) sensing of hydroxy double salt supported gold nanoclusters. AB - In this paper, a complex of Zn-containing hydroxy double salt (Zn-HDS) supported gold nanoclusters (AuNCs) has been synthesized. The formation of the complex (denoted as the AuNCs/Zn-HDS complex) has been analyzed by Transmission Electron Microscopy (TEM), IR spectroscopy and X-ray Photoelectron Spectroscopy (XPS). It is noteworthy that the AuNCs/Zn-HDS complex emits green fluorescence and the quantum yield is 7.6%. Based on the fluorescence quenching effect, the AuNCs/Zn HDS complex has been employed for the sensitive detection of Ag(+) and the limit of detection is 2.32 nM. The mechanisms of fluorescence generation and quenching are discussed in detail. PMID- 26868302 TI - Synthetic collective intelligence. AB - Intelligent systems have emerged in our biosphere in different contexts and achieving different levels of complexity. The requirement of communication in a social context has been in all cases a determinant. The human brain, probably co evolving with language, is an exceedingly successful example. Similarly, social insects complex collective decisions emerge from information exchanges between many agents. The difference is that such processing is obtained out of a limited individual cognitive power. Computational models and embodied versions using non living systems, particularly involving robot swarms, have been used to explore the potentiality of collective intelligence. Here we suggest a novel approach to the problem grounded in the genetic engineering of unicellular systems, which can be modified in order to interact, store memories or adapt to external stimuli in collective ways. What we label as Synthetic Swarm Intelligence defines a parallel approach to the evolution of computation and swarm intelligence and allows to explore potential embodied scenarios for decision making at the microscale. Here, we consider several relevant examples of collective intelligence and their synthetic organism counterparts. PMID- 26868303 TI - Three-dimensional full-field X-ray orientation microscopy. AB - A previously introduced mathematical framework for full-field X-ray orientation microscopy is for the first time applied to experimental near-field diffraction data acquired from a polycrystalline sample. Grain by grain tomographic reconstructions using convex optimization and prior knowledge are carried out in a six-dimensional representation of position-orientation space, used for modelling the inverse problem of X-ray orientation imaging. From the 6D reconstruction output we derive 3D orientation maps, which are then assembled into a common sample volume. The obtained 3D orientation map is compared to an EBSD surface map and local misorientations, as well as remaining discrepancies in grain boundary positions are quantified. The new approach replaces the single orientation reconstruction scheme behind X-ray diffraction contrast tomography and extends the applicability of this diffraction imaging technique to material micro-structures exhibiting sub-grains and/or intra-granular orientation spreads of up to a few degrees. As demonstrated on textured sub-regions of the sample, the new framework can be extended to operate on experimental raw data, thereby bypassing the concept of orientation indexation based on diffraction spot peak positions. This new method enables fast, three-dimensional characterization with isotropic spatial resolution, suitable for time-lapse observations of grain microstructures evolving as a function of applied strain or temperature. PMID- 26868298 TI - Coronaviruses - drug discovery and therapeutic options. AB - In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. PMID- 26868304 TI - Therapeutic approach to target mesothelioma cancer cells using the Wnt antagonist, secreted frizzled-related protein 4: Metabolic state of cancer cells. AB - Malignant mesothelioma (MM) is an aggressive cancer, characterized by rapid progression, along with late metastasis and poor patient prognosis. It is resistant to many forms of standard anti-cancer treatment. In this study, we determined the effect of secreted frizzled-related protein 4 (sFRP4), a Wnt pathway inhibitor, on cancer cell proliferation and metabolism using the JU77 mesothelioma cell line. Treatment with sFRP4 (250 pg/ml) resulted in a significant reduction of cell proliferation. The addition of the Wnt activator Wnt3a (250 pg/ml) or sFRP4 had no significant effect on ATP production and glucose utilisation in JU77 cells at both the 24 and 48 h time points examined. We also examined their effect on Akt and Glycogen synthase kinase-3 beta (GSK3beta) phosphorylation, which are both important components of Wnt signalling and glucose metabolism. We found that protein phosphorylation of Akt and GSK3beta varied over the 24h and 48 h time points, with constitutive phosphorylation of Akt at serine 473 (pAkt) decreasing to its most significant level when treated with Wnt3a+sFRP4 at the 24h time point. A significant reduction in the level of Cytochrome c oxidase was observed at the 48 h time point, when sFRP4 and Wnt3a were added in combination. We conclude that sFRP4 may function, in part, to reduce/alter cancer cell metabolism, which may lead to sensitisation of cancer cells to chemotherapeutics, or even cell death. PMID- 26868306 TI - A Model-Based Product Evaluation Protocol for Comparison of Safety-Engineered Protection Mechanisms of Winged Blood Collection Needles. AB - OBJECTIVE: To evaluate differences in product characteristics and user preferences of safety-engineered protection mechanisms of winged blood collection needles. DESIGN: Randomized model-based simulation study. SETTING: University medical center. PARTICIPANTS: A total of 33 third-year medical students. METHODS: Venipuncture was performed using winged blood collection needles with 4 different safety mechanisms: (a) Venofix Safety, (b) BD Vacutainer Push Button, (c) Safety Multifly, and (d) Surshield Surflo. Each needle type was used in 3 consecutive tries: there was an uninstructed first handling, then instructions were given according to the operating manual; subsequently, a first trial and second trial were conducted. Study end points included successful activation, activation time, single-handed activation, correct activation, possible risk of needlestick injury, possibility of deactivation, and preferred safety mechanism. RESULTS: The overall successful activation rate during the second trial was equal for all 4 devices (94%-100%). Median activation time was (a) 7 s, (b) 2 s, (c) 9 s, and (d) 7 s. Single-handed activation during the second trial was (a) 18%, (b) 82%, (c) 15%, and (d) 45%. Correct activation during the second trial was (a) 3%, (b) 64%, (c) 15%, and (d) 39%. Possible risk of needlestick injury during the second trial was highest with (d). Possibility of deactivation was (a) 0%, (b) 12%, (c) 9%, and (d) 18%. Individual preferences for each system were (a) 11, (b) 17, (c) 5, and (d) 0. The main reason for preference was the comprehensive safety mechanism. CONCLUSION: Significant differences exist between safety mechanisms of winged blood collection needles. PMID- 26868305 TI - Improving Critical View of Safety in Laparoscopic Cholecystectomy by Teaching Interventions. AB - BACKGROUND: Guidelines recommend obtaining a critical view of safety (CVS) during laparoscopic cholecystectomies to prevent serious bile duct injuries. We sought to evaluate the results of a teaching intervention for surgeons and residents about achieving CVS. METHODS: The intervention consisted of a lecture followed by a handout on CVS along with a teaching video on how to perform a laparoscopic cholecystectomy and common pitfalls encountered. After 9 months, the whole intervention was repeated. We retrospectively collected demographic data, details about the procedure, and complications for 316 consecutive patients who underwent laparoscopic cholecystectomy and reviewed available videos of laparoscopic cholecystectomy for 229 of these patients. Videos before and after the teaching interventions were reviewed by 2 gastrointestinal surgeons regarding whether CVS was reached, and Kappa statistics were calculated to measure inter-rater agreement. RESULTS: Most patients (average age 51 years) underwent laparoscopic cholecystectomy for symptomatic cholelithiasis (n = 171, 75%). CVS was reached in 69% of the preteaching intervention patients (n = 54), in 73% after the first teaching intervention (n = 75) and in 82% after the second intervention (n = 100) (not significant, overall p = 0.070). The complication rates were 24% (n = 13) before the intervention, 19% (n = 14) after the first teaching intervention, and 17% (n = 17) after the second intervention (not significant). In these groups, 1, 3, and 5 cases, correspondingly, with biliary injury were identified. All but 1 complication was related to a type A biliary injury. CONCLUSION: After the teaching interventions, the complication rate and the rate of reaching CVS did not improve significantly. To improve surgeons' success in reaching CVS, more personal interventions may be more effective than the group intervention we used in this study. The next step may be to present surgeons and residents who have a low CVS rate directly with their personal results. PMID- 26868307 TI - The characterization of hematopoietic tissue in adult Chinese mitten crab Eriocheir sinensis. AB - Invertebrates rely on the efficient innate immune mechanisms against invaders, in which the continuous production of hemocytes (hematopoiesis) is indispensable. In the present study, the hematopoietic tissue (HPT) from Chinese mitten crab Eriocheir sinensis was identified and characterized. It was a thin and non transparent sheet located at the dorsolateral side of the stomach, which was composed of a series of ovoid lobules. Each lobule was surrounded by connective tissue containing a large amount of spherical cells with big nucleus. In HPT, the cells were full of mitochondria and granules, and DNA replication was detected in some cells by EdU labeling technique. Cell proliferation was observed in HPT by transmission electron microscope (TEM). The distribution of two transcription factors, GATA1 and RUNX1, were examined by human GATA1 and RUNX1 antibodies, respectively. Three homologues of RUNX1 were detected in the HPT while no signal of RUNX1 was observed in hemocytes, and GATA1 was detected in both HPT and some hemocytes. The mRNA transcript of a novel hematopoiesis related cytokine EsAst was detected in hepatopancreas and hemocytes, but it was no detectable in HPT. The mRNA expression level of EsAst in hepatopancreas was 1.38-fold higher than that in hemocytes. Total hemocytes counts were related to the mRNA expression level of EsAst post Aeromonas hydrophila challenge. The results suggested that the stem cells in the hematopoietic tissue of Chinese mitten crab E. sinensis were regulated by transcriptional and humoral factors to generate hemocytes. PMID- 26868308 TI - Microwave-Assisted Copper-Catalyzed Oxidative Cyclization of Acrylamides with Non Activated Ketones. AB - An operationally simple and efficient microwave-assisted protocol for the oxidative cyclization of acrylamide derivatives with non-activated ketones to generate 3,3-disubstituted oxindoles is described. The reaction proceeds by a copper-catalyzed tandem radical addition/cyclization strategy and tolerates a series of functional groups with moderate to excellent yields. PMID- 26868309 TI - Mental health in Europe's Syrian refugee crisis. PMID- 26868310 TI - A National Survey of Undergraduate Suture and Local Anesthetic Training in the United Kingdom. AB - BACKGROUND: Suturing is a skill expected to be attained by all medical students on graduation, according to the General Medical Council's (GMC) Tomorrow's Doctors. There are no GMC recommendations for the amount of suture training required at medical school nor the level of competence to be achieved. This study examines the state of undergraduate suture training by surveying a sample of medical students across the United Kingdom. METHODS: We distributed a survey to 17 medical schools to be completed by undergraduates who have undergone curricular suture training. The survey included questions relating to career intention, hours of curricular suture training, hours of additional paid training, confidence in performing various suture techniques and knowledge of their indications. We also asked about the students' perceived proficiency at injecting local anesthetic and their overall opinion of medical school suture training. RESULTS: We received responses from 705 medical students at 16 UK medical schools. A total of 607 (86.1%) medical students had completed their scheduled curricular suture training. Among them, 526 (86.5%) students reported inadequate suture training in medical school and 133 (21.9%) students had paid for additional training. Results for all competence markers were significantly lower than the required GMC standards (p < 0.001). Students who had paid for additional training were significantly more confident across all areas examined (p < 0.001). CONCLUSIONS: Our study identified a deficiency in the curricular suture training provided to the medical students surveyed. These findings suggest that medical schools should provide more opportunities for students to develop their suturing skills to achieve the GMC standard. PMID- 26868311 TI - An Experiential Learning Model Facilitates Learning of Bedside Ultrasound by Preclinical Medical Students. AB - OBJECTIVE: To examine the effects of an experiential learning model of ultrasound training on preclinical medical students' knowledge and practice of Focused Assessment with Sonography for Trauma (FAST) examination. METHODS: The study was conducted in 2 phases. In phase 1, first- and second-year medical students participated in a 45-minute didactic presentation and subsequent 1-hour hands-on practice followed by 3-5 precepted FAST examinations in the emergency department. A pretest or posttest design was used to examine the participants' knowledge interpreting ultrasound images of the FAST examination. In phase 2, students performed FAST scans on patients with abdominal complaints under the supervision of emergency ultrasound faculty over a 1-year period. The participants were scored based on window acquisition, quality of images, accuracy of FAST scan interpretation, confidence level rated by participant, and supervising attending physician. RESULTS: In phase 1, 68 novice medical students participated in 11 training sessions offered over a 1-year period. Students showed significant improvement in basic ultrasound and abdominal anatomy knowledge. The mean score improved from a pretest score of 5.8 of 10 (95% CI: 5.3-6.2) to a posttest score of 7.3 of 10 (95% CI: 7-7.6). The students also demonstrated a significant improvement in FAST image interpretation (pretest of 6.2 [95% CI: 5.9-6.6] and posttest of 7.6 [95% CI: 7.1-7.9]). In phase 2, 22 students performed 304 FAST examinations on patients. At the beginning of their training when they performed less than 10 FAST scans, students were able to complete the right upper quadrant view in 88.9%, left upper quadrant view in 69.7%, subxiphoid in 64.7%, and pelvic view in 70% of scans. Across all views of the FAST examination, increasing level of practice was associated with improvement in successfully completing the examination. The absolute increase in the proportion experiencing success in the right upper quadrant view was 1.6%, 3.6%, and 6.2% for the 10-19, 20-29, and >30 groups, respectively, of which none were statistically significant. However, the improvements in the left upper quadrant view was 12.7%, 11.6%, 15.7% for the 10 19, 20-29, and >30 groups, respectively. In all views, performing >30 examinations more than doubled the odds of successfully completing the examination. CONCLUSION: An experiential learning model of ultrasound training consisting of brief didactic presentation, practice FAST examinations on normal models, and proctored examinations on patients is an effective way to teach preclinical medical students basic ultrasound skills. PMID- 26868312 TI - Assessing the Nontechnical Skills of Surgical Trainees: Views of the Theater Team. AB - OBJECTIVE: This study aims to explore the views of members of theater teams regarding the proposed introduction of a workplace-based assessment of nontechnical skills of surgeons (NOTSS) into the Intercollegiate Surgical Curriculum Programme in the United Kingdom. In addition, the previous training and familiarity of the members of the surgical theater team with the concept and assessment of NOTSS would be evaluated. DESIGN: A regional survey of members of theater teams (consultant surgeons, anesthetists, scrub nurses, and trainees) was performed at 1 teaching and 2 district general hospitals in South Yorkshire. RESULTS: There were 160 respondents corresponding to a response rate of 81%. The majority (77%) were not aware of the NOTSS assessment tool with only 9% of respondents reporting to have previously used the NOTSS tool and just 3% having received training in NOTSS assessment. Overall, 81% stated that assessing NOTSS was as important as assessing technical skills. Trainees attributed less importance to nontechnical skills than the other groups (p <= 0.016). Although opinion appears divided as to whether the presence of a consultant surgeon in theater could potentially make it difficult to assess a trainee's leadership skills and decision-making capabilities, overall 60% agree that the routine use of NOTSS assessment would enhance safety in the operating theater and 80% agree that the NOTSS tool should be introduced to assess the nontechnical skills of trainees in theater. However, a significantly lower proportion of trainees (45%) agreed on the latter compared with the other groups (p = 0.001). CONCLUSIONS: Our survey demonstrates acceptability among the theater team for the introduction of the NOTSS tool into the surgical curriculum. However, lack of familiarity highlights the importance of faculty training for assessors before such an introduction. PMID- 26868313 TI - Assessment of Developmental Progress Using an Objective Structured Clinical Examination-Simulation Hybrid Examination for Obstetrics and Gynecology Residents. AB - OBJECTIVE: The Test of Integrated Professional Skills (TIPS) is an objective structured clinical examination-simulation hybrid examination that assesses resident integration of technical, cognitive, and affective skills in Obstetrics and Gynecology (OBGYN) residents. The aim of this study was to analyze performance patterns and reactions of residents to the test to understand how it may fit within a comprehensive assessment program. DESIGN: A retrospective, mixed methods review of the design and implementation of the examination, patterns of performance of trainees at different levels of training, focus group data, and description of use of TIPS results for resident remediation and curriculum development. SETTING: OBGYN residents at New York University Langone Medical Center, a tertiary-care, urban academic health center. PARTICIPANTS: OBGYN residents in all years of training, postgraduate year-1 through postgraduate year, all residents completing the TIPS examination and consenting to participate in focus groups were included. RESULTS: In all, 24 residents completed the TIPS examination. Performance on the examination varied widely among individuals at each stage of training, and did not follow developmental trends, except for technical skills. Cronbach alpha for both standardized patient and faculty ratings ranged from 0.69 to 0.84, suggesting internal consistency. Focus group results indicated that residents respond to the TIPS examination in complex ways, ranging from anxiety about performance to mixed feelings about how to use the data for their learning. CONCLUSION: TIPS assesses a range of attributes, and can support both formative and summative evaluation. Lack of clear developmental differences and wide variation in performance by learners at the same level of training support the argument for individualized learning plans and competency based education. PMID- 26868314 TI - Do Three-dimensional Visualization and Three-dimensional Printing Improve Hepatic Segment Anatomy Teaching? A Randomized Controlled Study. AB - INTRODUCTION: Hepatic segment anatomy is difficult for medical students to learn. Three-dimensional visualization (3DV) is a useful tool in anatomy teaching, but current models do not capture haptic qualities. However, three-dimensional printing (3DP) can produce highly accurate complex physical models. Therefore, in this study we aimed to develop a novel 3DP hepatic segment model and compare the teaching effectiveness of a 3DV model, a 3DP model, and a traditional anatomical atlas. MATERIALS AND METHODS: A healthy candidate (female, 50-years old) was recruited and scanned with computed tomography. After three-dimensional (3D) reconstruction, the computed 3D images of the hepatic structures were obtained. The parenchyma model was divided into 8 hepatic segments to produce the 3DV hepatic segment model. The computed 3DP model was designed by removing the surrounding parenchyma and leaving the segmental partitions. Then, 6 experts evaluated the 3DV and 3DP models using a 5-point Likert scale. A randomized controlled trial was conducted to evaluate the educational effectiveness of these models compared with that of the traditional anatomical atlas. RESULTS: The 3DP model successfully displayed the hepatic segment structures with partitions. All experts agreed or strongly agreed that the 3D models provided good realism for anatomical instruction, with no significant differences between the 3DV and 3DP models in each index (p > 0.05). Additionally, the teaching effects show that the 3DV and 3DP models were significantly better than traditional anatomical atlas in the first and second examinations (p < 0.05). Between the first and second examinations, only the traditional method group had significant declines (p < 0.05). CONCLUSION: A novel 3DP hepatic segment model was successfully developed. Both the 3DV and 3DP models could improve anatomy teaching significantly. PMID- 26868315 TI - Relevancy of an In-Service Examination for Core Knowledge Training in a Surgical Subspecialty. AB - OBJECTIVE: To facilitate knowledge acquisition during plastic surgery residency, we analyzed the breast curriculum on the Plastic Surgery In-Service Training Exam (PSITE). DESIGN: Breast-related questions on 6 consecutive PSITEs were analyzed (2008-2013). Topics were categorized by the content outline for the American Board of Plastic Surgery written board examination. Question vignettes were classified by taxonomy and clinical setting. References for correct answer choices were categorized by source and publication lag. RESULTS: A total of 136 breast-related questions were analyzed (136/1174, 12%). Questions tended to appear more in the Breast and Cosmetic (75%) section than the Comprehensive (25%) section (p < 0.001). Most question vignettes were written in a clinical setting (64%, p < 0.001). Question taxonomy was evenly distributed among recall (34%), interpretation (28%), and decision-making (37%, p > 0.05). Only 6% of questions required photographic evaluation. Breast-related topics focused on esthetic problems (35%), traumatic deformities (22%), and tumors (21%). Answer references comprised 293 citations to 63 unique journals published a median of 6 years before PSITE administration. Plastic and Reconstructive Surgery (57%) was the most cited journal (p < 0.001) and Surgery of the Breast: Principles and Art by Spear was the most referenced textbook (22%). CONCLUSIONS: The PSITE affords a curriculum that reflects breast-related topics on the American Board of Plastic Surgery written board examination. These data may optimize knowledge acquisition in esthetic and reconstructive breast surgery. PMID- 26868316 TI - The Effect of Self-Citations on the Hirsch Index Among Full-Time Academic Hand Surgeons. AB - OBJECTIVE: To assess the magnitude of self-citation among a cohort of academic hand surgeons and estimate the effect of self-citation on the Hirsch index (h index). DESIGN: Cross-sectional study. SETTING: Johns Hopkins Hospital, Department of Plastic and Reconstructive Surgery, Division of Hand Surgery. RESULTS: The study sample comprised 364 full-time academic hand surgeons. Study subjects had an average of 45 +/- 73 publications. The mean total number of citations was 800 +/- 1738, the median number of self-citations was 2.5 (interquartile range [IQR]: 0-14.8), and the average frequency of self-citation was 2.2% +/- 3.7%. Older surgeons were slightly less likely to self-cite (coefficient = 0.07; p = 0.001). Furthermore, as the total number of publications increased, the frequency of self-citation increased (coefficient = 0.03; p < 0.001). The h-index increased because of self-citation in 57 surgeons (15.7%). After adjusting for American Society for Surgery of the Hand status and academic rank, increasing rates of self-citation were associated with an increase in the h index. Surgeons with 7 or more self-citations were more likely to have their h index influenced by self-citation. CONCLUSIONS: The rate of self-citation among full-time academic hand surgeons affiliated with fellowship programs is fairly low. For most of the surgeons, self-citation did not affect the h-index. PMID- 26868317 TI - The Transferability of Generic Minimally Invasive Surgical Skills: Is There Crossover of Core Skills Between Laparoscopy and Arthroscopy? AB - OBJECTIVE: The primary objective was observing transferability of minimally invasive surgical skills between virtual reality simulators for laparoscopy and arthroscopy. Secondary objectives were to assess face validity and acceptability. DESIGN: Prospective single-blinded crossover randomized controlled trial. SETTING: MSk Laboratory, Imperial College London. PARTICIPANTS: Student doctors naive to simulation and minimally invasive techniques. METHODS: A total of 72 medical students were randomized into 4 groups (2 control groups and 2 training groups), and tested on haptic virtual reality simulators. Group 1 (control; n = 16) performed a partial laparoscopic cholecystectomy and Group 2 (control; n = 16) performed a diagnostic knee arthroscopy. Both groups then repeated the same task a week later. Group 3 (training; n = 20) completed a partial laparoscopic cholecystectomy, followed by an arthroscopic training program, and repeated the laparoscopic cholecystectomy a week later. Group 4 (training; n = 20) performed a diagnostic knee arthroscopy, followed by a laparoscopic training program, and then repeated the initial arthroscopic test a week later. The time taken, instrument path length, and speed were recorded for each participant and analyzed. RESULTS: Time taken for task: All 4 cohorts were significantly quicker on their second attempt but the 2 training groups outperformed the 2 control groups, with the laparoscopy-trained group improving the most (p < 0.05). Economy of movement: All cohorts had a significant improvement in left hand path length (p < 0.01) but there was no difference for right hand path length. Left hand speed: Only the 2 training groups showed significant improvement with the laparoscopy-trained group improving the most (p < 0.05). Right hand speed: All cohorts improved significantly with the laparoscopy-trained group improving the most (p < 0.05). Face validity and acceptability were established for both simulators. CONCLUSION: This study showed that minimally invasive surgical skills learnt on a laparoscopy simulator are transferable to arthroscopy and vice versa, with greater effect after training on the laparoscopy simulator. PMID- 26868319 TI - The religious brain. AB - This paper is a critical review of anthropology and cognitive science that proposes social, cognitive, and neural mechanisms that convert culturally transmitted ideas into beliefs, discussed in relation to Geertz's classic definition of religion ('Religion as a cultural system', 1966). Literal and analogical uses of language, and a capacity for mentalizing thought, allow the creation of systems of symbols that vary between groups, contributing to the systematic group-level differences that we refer to as 'culture'. A combination of social referencing, mentalizing, and emotion perception enables enculturation to occur by attention to stable, repetitive conjunctions of meanings and emotions in the social environment, promoting the formation of cognitive-affective schemata. In addition to informal enculturation in routine social interaction, cultural systems such as religions organize and protect transmission of valued knowledge. Religious rituals are culturally invented symbolic displays that transmit conceptions of the world and imbue them with emotional and motivational significance. Two kinds of ritual are distinguished: high frequency, low arousal rituals belonging to a 'doctrinal' religious mode, and low frequency, high arousal rituals belonging to an 'imagistic' religious mode ( Whitehouse 2000 ). 'Doctrinal' rituals allow the extraction of semantic memories and associated emotions through repeated participation and exposure. 'Imagistic' rituals are particularly associated with intense emotion, episodic memory formation, and the formation of social ties. Religious rituals, especially imagistic rituals, employ two major strategies to convey conceptions of the world and invest them with a heightened sense of reality and emotion: (1) a 'sensory' route evokes salient thought and experience by orchestrating multiple reinforcing social-emotional signals and other stimuli, engaging attention, emotion, and arousal; (2) a 'semantic' route uses enigmatic verbal and non-verbal symbols to engage an analogical/right hemispheric processing strategy to make sense of what is authoritatively presented as real but incompletely understood. Both routes are hypothesized to activate the mesolimbic dopamine system amongst other components of cognitive-affective processing, so that the 'moods and motivations' evoked by the ritual performance seem 'uniquely realistic'. These social, cognitive, and neural processes constitute ways in which religious ideas are turned into convictions. PMID- 26868318 TI - Training With Curved Laparoscopic Instruments in Single-Port Setting Improves Performance Using Straight Instruments: A Prospective Randomized Simulation Study. AB - OBJECTIVE: Lately single-port surgery is becoming a widespread procedure, but it is more difficult than conventional laparoscopy owing to the lack of triangulation. Although, these operations are also possible with standard laparoscopic instruments, curved instruments are being developed. The aims of the study were to identify the effect of training on a box trainer in single-port setting on the quality of acquired skills, and transferred with the straight and curved instruments for the basic laparoscopic tasks, and highlight the importance of a special laparoscopic training curriculum. DESIGN: A prospective study on a box trainer in single-port setting was conducted using 2 groups. Each group performed 2 tasks on the box trainer in single-port setting. Group-S used conventional straight laparoscopic instruments, and Group-C used curved laparoscopic instruments. Learning curves were obtained by daily measurements recorded in 7-day sessions. On the last day, the 2 groups changed instruments between each other. SETTING: 1st Department of Surgery, Semmelweis University of Medicine from Budapest, Hungary, a university teaching hospital. PARTICIPANTS: In all, 20 fifth-year medical students were randomized into 2 groups. None of them had any laparoscopic or endoscopic experience. Participation was voluntary. RESULTS: Although Group-S performed all tasks significantly faster than Group-C on the first day, the difference proved to be nonsignificant on the last day. All participants achieved significantly shorter task completion time on the last day than on the first day, regardless of the instrument they used. Group-S showed improvement of 63.5%, and Group-C 69.0% improvement by the end of the session. After swapping the instruments, Group-S reached significantly higher task completion time with curved instruments, whereas Group-C showed further progression of 8.9% with straight instruments. CONCLUSIONS: Training with curved instruments in a single-port setting allows for a better acquisition of skills in a shorter period. For this reason, there is a need for proficiency-based conventional, but also for a single-port, laparoscopic training curriculum in general surgery residency education. PMID- 26868320 TI - Human and spiritual agency in Angami healing. AB - Despite the thought-provoking theological and philosophical implications of the adage urging the healer to heal him/herself, medical anthropology has, with some notable exceptions, given relatively little attention to the problems of well being experienced by healers themselves, as distinct from those of their patients. This paper focuses on the conflicts experienced by men and women who become healers and how they try to resolve them. The case taken is of the Angami people of Nagaland, northeastern India. There are broadly two kinds of healer, each of whom is subject to contrasting pressures and conflicts. Shamans depend on tutelary spirits who may at various points control the shaman him or herself, who may have been initially reluctant to become a shaman. Other healers such as herbalists and masseurs may sometimes use but do not rely on tutelary spirits and draw instead on their own non-divinational skills. An increasing number of such healers have become Christian and are obliged to adapt their practices accordingly, including the divinity of a new God, sometimes denying a previous personal or family connection with shamanism. At issue in both cases is a struggle between human and divine agency, which, writ large, is a struggle between human self-determination and external forces of control, this being possibly reflected in the fact that Nagaland has for many years been the scene of an armed struggle against the Indian government for political autonomy. PMID- 26868321 TI - Healing rituals. AB - This paper poses a theoretical question: how, if at all, can 'critical medical anthropology' and 'performance theory' be combined? More specifically, the author discusses the relative advantages and disadvantages of each, with respect to a healing cult in the Central Himalayas of North India. The paper has four parts: first, an ethnographic description of the cult itself; second, a brief introduction to critical medical anthropology; third, a short discussion of the performative approach to healing rituals; and finally, an attempt to combine the two approaches. The author concludes that the two approaches can indeed combined, so long as one recognizes (1) that caste and gender are also appropriate objects for critical medical anthropology; and (2) that aesthetics is always already political. PMID- 26868322 TI - Towards an ethnography of Indian homeopathy. AB - Despite its large number of practitioners, medical anthropology has given little attention to Indian homeopathy. In historical accounts, homeopathy's popularity is explained by its position as a modern, yet non-colonial form of medicine, which became indigenized during the last 150 years. Other scholars argue that homeopathic concepts converge with Indian ideas on healing. However, few empirical data have been gathered on homeopathic practice in contemporary India. In this paper, we explore the perspectives of college-trained homeopaths in urban West Bengal. How strongly do they feel indebted to classical and canonical homeopathic writings? Can we observe attempts of indigenizing homeopathy by blending it with common ideas of Indian medical culture? While the homeopaths in our study report practising an orthodox version of homeopathy, we can also identify creative solutions when they are responding to their patients' expectations: conforming to the idea of single-remedy prescription by simultaneous use of placebos, short-cut homeopathic anamnesis, complementing homeopathic drugs with therapeutic nutritional advice, and developing a system of seasonal drugs are all evidence for silent hybridization of homeopathic and local ideas. In the homeopathic consultation, time pressure becomes a significant challenge and Bengali homeopaths grasp the most important homeopathic symptoms quickly. PMID- 26868323 TI - 'He's telling us something'. AB - Drawing on in-depth interviews with patients and participant observation notes from a cancer support group and outpatients department, we analyse the experiences of Australian-born and immigrant women with gynaecological cancer to describe cancer diagnosis disclosures from the patients' perspectives and examine women's treatment decision-making. Data suggest that most women did not question the surgeon's recommendation and assumed a passive role in treatment decision making. The contextual factors which impacted on this pattern were the unavailability of an alternative biomedical treatment path, the perception of the metropolitan hospital as a centre of clinical excellence with extensive experience in treating women with gynaecological cancer, and lay understandings of the nature of gynaecological cancer as 'a killer'. We also discuss the circumstances under which a few women took on the role of primary decision-maker. PMID- 26868326 TI - Automated microaneurysm detection in diabetic retinopathy using curvelet transform. AB - Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies. PMID- 26868327 TI - Response to Letter to the Editor: Toward a Multifactorial Model of Caries Formation. PMID- 26868328 TI - Letter to the Editor: Toward a Multifactorial Model of Caries Formation. PMID- 26868329 TI - Use of a nictitating membrane flap for treatment of feline acute corneal hydrops 21 eyes. AB - OBJECTIVE: To evaluate the effectiveness of the use of a nictitating membrane flap (NMF) as therapy in 19 cats (21 eyes) affected with feline acute corneal hydrops (FACH). METHODS: Medical records from 19 cats diagnosed with FACH and treated with a NMF were retrospectively evaluated. Information was collected from multiple veterinary hospitals and included signalment, medical history, therapy, and ocular outcome. RESULTS: Breeds included 13 Domestic Shorthairs, 2 Exotic Shorthairs, 2 Maine Coons, 1 Persian, and 1 Domestic Medium Hair. Two cats were bilaterally affected. Median age of cats was 3.2 years (range 0.26-15 years). Eleven patients were spayed females, 6 were neutered males, and 2 were intact males. Topical steroids were previously administered in 5 (23.8%) eyes; oral steroids were previously administered in 7 cats (36.8% of patients); three patients received both oral and topical steroids. Thirteen of 21 (61.9%) eyes had a history of ocular disease including ulcerative and nonulcerative keratitis, anterior uveitis, corneal sequestrum, conjunctivitis, and glaucoma. Median duration of NMF was 15 days (range 6-30 days). Follow-up ranged from 12 to 1601 days (median 169 days). Corneal perforation occurred in 1 (4.7%) eye and was successfully repaired. One lesion (4.7%) in a diabetic patient did not resolve. Nineteen of the treated eyes (90.5%) resolved with no complications. CONCLUSIONS: A nictitating membrane flap successfully treated 90.5% of FACH eyes (89.5% of patients). PMID- 26868330 TI - Prognostic Significance of Preoperative Serum Lactate Dehydrogenase in Upper Urinary Tract Urothelial Carcinoma. AB - BACKGROUND: Upper urinary tract urothelial carcinoma (UUTUC) is one of the uncommon malignancies lacking of prognostic indicators. Lactate dehydrogenase (LDH) has been demonstrated to correlate with clinical outcomes in human cancers. In this study, we aimed to evaluate the prognostic implication of the preoperative LDH in UUTUC. PATIENTS AND METHODS: A cohort of 100 UUTUC samples along with the preoperative LDH value was recruited from January 1990 to June 2011. The cutoff value was set at 245 u/L for the upper value of normal limitation. Univariate and multivariate analyses were conducted to determine the association of LDH with overall survival (OS) and disease-free survival (DFS). RESULTS: Kaplan-Meier analysis revealed that high level of LDH (> 245 u/L) was significantly associated with poor OS (P < .001) and DFS (P = .002). Multivariate Cox proportional analysis indicated LDH, controlled by vascular invasion, pathological stage, lymph node status, subsequent bladder tumor, tumor grade, tumor necrosis, architecture, and multifocality, was as an independent predictor of OS (hazard ratio, 3.181; 95% confidence interval, 1.223-8.276; P = .018) and DFS (hazard ratio, 3.041; 95% confidence interval, 1.247-7.417; P = .015). Stratified showed that elevated serum LDH was correlated with the worse OS in patients without lymph node metastasis (P = .002) and those at advanced pathological stage (P < .001). CONCLUSION: The preoperative LDH was an independent prognostic factor for patients with UUTUC and could be used as a risk factor to predict the tumor aggressiveness. PMID- 26868331 TI - Mitochondrial comparative genomics and phylogenetic signal assessment of mtDNA among arbuscular mycorrhizal fungi. AB - Mitochondrial (mt) genes, such as cytochrome C oxidase genes (cox), have been widely used for barcoding in many groups of organisms, although this approach has been less powerful in the fungal kingdom due to the rapid evolution of their mt genomes. The use of mt genes in phylogenetic studies of Dikarya has been met with success, while early diverging fungal lineages remain less studied, particularly the arbuscular mycorrhizal fungi (AMF). Advances in next-generation sequencing have substantially increased the number of publically available mtDNA sequences for the Glomeromycota. As a result, comparison of mtDNA across key AMF taxa can now be applied to assess the phylogenetic signal of individual mt coding genes, as well as concatenated subsets of coding genes. Here we show comparative analyses of publically available mt genomes of Glomeromycota, augmented with two mtDNA genomes that were newly sequenced for this study (Rhizophagus irregularis DAOM240159 and Glomus aggregatum DAOM240163), resulting in 16 complete mtDNA datasets. R. irregularis isolate DAOM240159 and G. aggregatum isolate DAOM240163 showed mt genomes measuring 72,293bp and 69,505bp with G+C contents of 37.1% and 37.3%, respectively. We assessed the phylogenies inferred from single mt genes and complete sets of coding genes, which are referred to as "supergenes" (16 concatenated coding genes), using Shimodaira-Hasegawa tests, in order to identify genes that best described AMF phylogeny. We found that rnl, nad5, cox1, and nad2 genes, as well as concatenated subset of these genes, provided phylogenies that were similar to the supergene set. This mitochondrial genomic analysis was also combined with principal coordinate and partitioning analyses, which helped to unravel certain evolutionary relationships in the Rhizophagus genus and for G. aggregatum within the Glomeromycota. We showed evidence to support the position of G. aggregatum within the R. irregularis 'species complex'. PMID- 26868332 TI - HOTAIR in relation to epithelial-mesenchymal transition and cancer stem cells in molecular subtypes of endometrial cancer. AB - BACKGROUND: Endometrial cancer (EC) is a hormone-related disease, showing highly diverse features of ER/PR/HER2 status-based molecular subtypes. Long noncoding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) has recently emerged as a key molecule in many cancers, triggering epithelial-mesenchymal transition (EMT) mediated cancer stem cell (CSC) formation, but little is known about its significance in EC. Thus, we aimed to investigate the clinical significance of HOTAIR itself in different molecular subtypes of EC and possible links between HOTAIR, EMT and CSC-related markers. METHODS: The study group included 156 consecutive, stage I-IV EC patients treated between 2000 and 2010. ER, PR and HER2 protein expression were examined by immunohistochemistry (IHC) on tissue microarrays. RT-qPCR was used to analyze the expression levels of HOTAIR, EMT related genes - SNAIL and SLUG - and the CSCs marker CD133. RESULTS: Molecular subtypes, defined as ER/PR+HER2+, ER/PR+HER2-, ER-PR-HER2+ and ER-PR-HER2-, occurred in 40.2%, 52.3%, 4.7% and 1.9% of cases, respectively. The expression of HOTAIR did not differ between the subtypes, but high HOTAIR expression correlated with shorter overall survival (p = 0.04) in the entire group. The expression levels of HOTAIR, SNAIL, SLUG and CD133 were similar in defined EC molecular subtypes. CONCLUSIONS: Our data do not confirm the role of HOTAIR in EMT-mediated CSC formation in EC. Neither does the diversity of EC molecular subtypes influence these processes. But HOTAIR expression could serve as an independent prognostic factor in EC. The clinical importance of the above discoveries requires further studies. PMID- 26868333 TI - Drafting biological material transfer agreement: a ready-to-sign model for biobanks and biorepositories. AB - PURPOSE: Due to the scarcity of publications, guidelines, and harmonization among national regulations, biobanks and institutions face practical and theoretical issues when drafting a material transfer agreement (MTA), the fundamental tool to regulate the successful exchange of biosamples and information. Frequently researchers do not execute MTAs because of a general lack of knowledge about this topic. It is thus critical to develop new models to prevent loss of traceability and opportunities both for researchers and biobanks, their exposure to various risks, and delays in transferring biomaterials. METHODS: Through the involvement of institutional groups and professionals with multidisciplinary expertise, we have drawn up a ready-to-sign MTA for the CRO-Biobank (the biobank of the National Cancer Institute, CRO, Aviano), a standardized template that can be employed as a ready-to-use model agreement. RESULTS: The team identified the essential components to be included in the MTA, which comprise i) permissions, liability and representations; ii) custodianship and distribution limitations; iii) appropriate use of materials, including biosafety concerns; iv) confidentiality, non-disclosure, and publications; v) intellectual property protection for both the provider and recipient. CONCLUSIONS: This paper aims to be an unabridged report (among the few works in the existing literature) providing a description of the whole process related to the formation of an MTA. Biobanks and institutions may consider adopting our ready-to-sign form as a standard model. The article discusses the most important issues tackled during the drafting of the document, thus proposing an operative approach for other institutions that face the same problems. PMID- 26868334 TI - HPV testing of biobanked liquid-based cytology - a validation study. AB - INTRODUCTION: The aim of the study was to investigate whether biobanked liquid based cytology (LBC) vaginal samples could be reanalyzed for the biomarkers HPV DNA and mRNA without loss of sensitivity. METHODS: One hundred LBC samples with ASCUS or CIN1 were tested for HPV DNA and mRNA before and after biobanking. DNA analysis targeted the viral genes E6 and E7, 12 high-risk and 2 low-risk HPV types together with the human control gene HBB, using real-time PCR. The Aptima HPV assay was used for mRNA analysis of 14 high-risk HPV types. RESULTS: With Aptima there was 84% agreement between results before and after biobanking. The sensitivity and specificity were 0.79 (95% CI, 0.68-0.88) and 0.94 (95% CI, 0.80 0.99), respectively. With the DNA-based method, the agreement between results was 87%, the sensitivity 0.85 (95% CI, 0.75-0.92) and the specificity 0.95 (95% CI, 0.77-1.00). Both methods presented a significant difference between positive results before and after biobanking; McNemar test: p = 0.004, p = 0.003, Cohen's kappa: 0.67 (95% CI, 0.53-0.81), 0.68 (95% CI, 0.52-0.84). Cycle threshold values for the DNA method were higher for all genotypes after biobanking, except for HPV 59. Some loss of sensitivity was seen after biobanking but the concordance between HPV detection before and after biobanking was good for both evaluated methods. CONCLUSIONS: Biobanking of LBC vaginal samples offers a good platform for HPV testing and could be extended to further molecular analyses. However, in order to ensure a valid test result a larger portion needs to be analyzed from the biobanked sample. PMID- 26868335 TI - Liquid cancer biopsy: the future of cancer detection? PMID- 26868336 TI - The promise and challenges of rare cancer research. PMID- 26868337 TI - Redefining "rare" in paediatric cancers. PMID- 26868338 TI - Cancer research: in need of introspection. PMID- 26868340 TI - Collages for cancer. PMID- 26868339 TI - The Mwanza Cancer Project. PMID- 26868341 TI - The Dream Lab. PMID- 26868342 TI - The Lake. PMID- 26868343 TI - Happygram. PMID- 26868344 TI - Prophylactic dexamethasone for radiation-induced bone-pain flare. PMID- 26868345 TI - Synergy in traditional Chinese medicine. PMID- 26868347 TI - Stereotactic radiotherapy or surgery for early-stage non-small-cell lung cancer. PMID- 26868346 TI - Prophylactic dexamethasone for radiation-induced bone-pain flare - Authors' reply. PMID- 26868348 TI - S-1 with leucovorin and oxaliplatin for advanced gastric cancer. PMID- 26868349 TI - Stereotactic radiotherapy or surgery for early-stage non-small-cell lung cancer - Authors' reply. PMID- 26868351 TI - Hemithoracic radiotherapy for mesothelioma: lack of benefit or lack of statistical power? - Authors' reply. PMID- 26868350 TI - Hemithoracic radiotherapy for mesothelioma: lack of benefit or lack of statistical power? PMID- 26868352 TI - Correction to Lancet Oncol 2016; 17: 248, 252. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. PMID- 26868353 TI - Correction to Lancet Oncol 2016; 17: 109. Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study. PMID- 26868354 TI - Rare cancers: a sea of opportunity. AB - Rare cancers, as a collective, account for around a quarter of all cancer diagnoses and deaths. Historically, they have been divided into two groups: cancers defined by their unusual histogenesis (cell of origin or differentiation state)--including chordomas or adult granulosa cell tumours--and histologically defined subtypes of common cancers. Most tumour types in the first group are still clinically and biologically relevant, and have been disproportionately important as sources of insight into cancer biology. By contrast, most of those in the second group have been shown to have neither defining molecular features nor clinical utility. Omics-based analyses have splintered common cancers into a myriad of molecularly, rather than histologically, defined subsets of common cancers, many of which have immediate clinical relevance. Now, almost all rare cancers are either histomolecular entities, which often have pathognomonic mutations, or molecularly defined subsets of more common cancers. The presence of specific genetic variants provides rationale for the testing of targeted drugs in rare cancers. However, in addition to molecular alterations, it is crucial to consider the contributions of both mutation and cell context in the development, biology, and behaviour of these cancers. Patients with rare cancers are disadvantaged because of the challenge of leading clinical trials in this setting due to poor accrual. However, the number of patients with rare cancers will only increase as more molecular subsets of common cancers are identified, necessitating a shift in the focus of clinical trials and research into these cancer types, which, by epidemiological definitions, will become rare tumours. PMID- 26868355 TI - The value of research collaborations and consortia in rare cancers. AB - Rare cancers are defined by an incidence of less than six per 100,000 people per year. They represent roughly 20% of all human cancers and are associated with worse survival than are so-called frequent tumours, because of delays to accurate diagnosis, inadequate treatments, and fewer opportunities to participate in clinical trials (because of a paucity of dedicated trials from both academic and industrial sponsors). In this Series paper, we discuss how these challenges can be addressed by research consortia and suggest the integration of these consortia with reference networks, which gather multidisciplinary expert centres, for management of rare tumours. PMID- 26868356 TI - Research methods to change clinical practice for patients with rare cancers. AB - Rare cancers are a growing group as a result of reclassification of common cancers by molecular markers. There is therefore an increasing need to identify methods to assess interventions that are sufficiently robust to potentially affect clinical practice in this setting. Methods advocated for clinical trials in rare diseases are not necessarily applicable in rare cancers. This Series paper describes research methods that are relevant for rare cancers in relation to the range of incidence levels. Strategies that maximise recruitment, minimise sample size, or maximise the usefulness of the evidence could enable the application of conventional clinical trial design to rare cancer populations. Alternative designs that address specific challenges for rare cancers with the aim of potentially changing clinical practice include Bayesian designs, uncontrolled n-of-1 trials, and umbrella and basket trials. Pragmatic solutions must be sought to enable some level of evidence-based health care for patients with rare cancers. PMID- 26868357 TI - Precision oncology: origins, optimism, and potential. AB - Imatinib, the first and arguably the best targeted therapy, became the springboard for developing drugs aimed at molecular targets deemed crucial to tumours. As this development unfolded, a revolution in the speed and cost of genetic sequencing occurred. The result--an armamentarium of drugs and an array of molecular targets--set the stage for precision oncology, a hypothesis that cancer treatment could be markedly improved if therapies were guided by a tumour's genomic alterations. Drawing lessons from the biological basis of cancer and recent empirical investigations, we take a more measured view of precision oncology's promise. Ultimately, the promise is not our concern, but the threshold at which we declare success. We review reports of precision oncology alongside those of precision diagnostics and novel radiotherapy approaches. Although confirmatory evidence is scarce, these interventions have been widely endorsed. We conclude that the current path will probably not be successful or, at a minimum, will have to undergo substantive adjustments before it can be successful. For the sake of patients with cancer, we hope one form of precision oncology will deliver on its promise. However, until confirmatory studies are completed, precision oncology remains unproven, and as such, a hypothesis in need of rigorous testing. PMID- 26868358 TI - Iterative error correction of long sequencing reads maximizes accuracy and improves contig assembly. AB - Next-generation sequencers such as Illumina can now produce reads up to 300 bp with high throughput, which is attractive for genome assembly. A first step in genome assembly is to computationally correct sequencing errors. However, correcting all errors in these longer reads is challenging. Here, we show that reads with remaining errors after correction often overlap repeats, where short erroneous k-mers occur in other copies of the repeat. We developed an iterative error correction pipeline that runs the previously published String Graph Assembler (SGA) in multiple rounds of k-mer-based correction with an increasing k mer size, followed by a final round of overlap-based correction. By combining the advantages of small and large k-mers, this approach corrects more errors in repeats and minimizes the total amount of erroneous reads. We show that higher read accuracy increases contig lengths two to three times. We provide SGA Iteratively Correcting Errors (https://github.com/hillerlab/IterativeErrorCorrection/) that implements iterative error correction by using modules from SGA. PMID- 26868359 TI - Chronic Recurrent Pseudophakic Endophthalmitis. PMID- 26868360 TI - Difference in Pacing Between Time- and Distance-Based Time Trials in Trained Cyclists. AB - The purpose of this study was to compare the pacing profiles between distance- and duration-based trials of short and long duration. Thirteen trained cyclists completed 2 time-based (6 and 30 min) and 2 distance-based (4 and 20 km) self paced cycling time trials. Participants were instructed to complete each trial with the highest average power output. Ratings of perceived exertion (RPEs) were measured throughout the trials. Average power output was not different between the 4-km and 6-min trials (324 +/- 46 vs 325 +/- 45 W; P = .96) or between the 20 km and 30-min trials (271 +/- 44 vs 267 +/- 38 W; P = .24). Power output was greater on commencement of the distance-based trials when short and long trials were analyzed together. Furthermore, the rate of decline in power output over the 1st 40% of the trial was greater in the 20-km trial than in the 30-min trial (P = .01) but not different between the 4-km and the 6-min trials (P = .13). RPE was greater in the 4-km trial than in the 6-min trial but not different between the 20-km and 30-min trials. These findings indicate that athletes commenced distance based time trials at relatively higher power outputs than a similar time-based trial. Such findings may result from discrete differences in our ability to judge or predict an exercise endpoint when performing time- and distance-based trials. PMID- 26868361 TI - Arthrobacter echini sp. nov., isolated from the gut of a purple sea urchin, Heliocidaris crassispina. AB - A novel strain, designated AM23T, was isolated from the gut of a purple sea urchin Heliocidaris crassispina collected from the coastal waters of the Korean island Dokdo. 16S rRNA gene sequence analysis showed that strain AM23T belonged to the genus Arthrobacter in the family Micrococcaceae and shared highest sequence similarity with Arthrobacter agilis DSM 20550T (98.77%). Strain AM23T was catalase-positive, oxidase-negative and grew optimally at 20 degrees C, in the presence of 1% (w/v) NaCl and at pH 7. The isolate was a Gram-stain-positive, non-motile, strictly aerobic and coccus-shaped bacterium. The major cellular fatty acids were anteiso-C15:0 and iso-C15:0. The polar lipids of strain AM23T were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unidentified glycolipid and four unidentified lipids. The components of the cell wall peptidoglycan were lysine, glutamic acid and alanine and the predominant cell-wall sugars were galactose, mannose, rhamnose and ribose. The major respiratory quinone was identified as menaquinone MK-9(H2). The genomic DNA G+C content was 67.3 mol% and the DNA-DNA hybridization values showed the strain shared less than 29% genomic relatedness with A. agilis DSM 20550T. The results of the phylogenetic, phenotypic and genotypic analysis indicate that strain AM23T represents a novel species in the genus Arthrobacter, for which the name Arthrobacter echini sp. nov. is proposed. The type strain is AM23T (=KACC 18260T=DSM 29493T). PMID- 26868362 TI - Assessment of the price-efficacy relationship for multiple brands of ceftriaxone sodium in Kabul: a cross-sectional study. AB - BACKGROUND: Most medicines are imported for health service practices in Afghanistan. A major concern for patients and practitioners in Kabul is the wide brand assortment and price range choices for the same drug. Ceftriaxone sodium is a broadly used antibiotic for infections caused by certain types of gram-positive and gram-negative bacteria. It is available in Kabul in a range of brands and prices. The objective of this study was to assess the relationship between cost/brand name and efficacy of this antibiotic. METHODS: 40 brands of ceftriaxone, obtained from Kabul's main pharmacy, were derived from 12 countries including Pakistan, Turkey, India, and China. Ten samples/brand were tested for efficacy by the minimal bactericidal concentration assay against a sensitive strain of Staphylococcus aureus according to the Clinical Institute and Laboratory Standards Protocols. Efficacy data were obtained by inoculating suspensions of S. aureus grown in Mueller-Hinton medium with various concentrations (6.25-800 mcg/ml) of each brand followed by incubation at 37 degrees C for 18-24 h. Aliquots of inoculated cultures were transferred to agar plates, incubated at 37 degrees C for 18-24 h and visible colonies counted. Results were analyzed using ANOVA, Student's t test, and Pearson correlation by SPSS 19. A p value <= 0.05 was considered statistically significant. RESULTS: Ceftriaxone sodium price varied from 20-270 Afghanis/brand (average price = 69.80 Afghanis/brand). Of the 40 brands tested, 10 (25 %) were not registered with the General Directorate of Pharmaceutical Affairs of the Ministry of Public Health in Afghanistan. More importantly, we observed no statistically significant difference in efficacy against S. aureus among these brands (p = 0.59). CONCLUSIONS: Our study showed no significant correlation among price, brand, and efficacy of ceftriaxone sodium against S. aureus, an important consideration when treating S. aureus infection in Afghanistan and elsewhere. Differences in brand prices are likely due to other factors including manufacturing and exportation costs, regulations of good manufacturing practice and seller's profit ceiling and patient preferences. Based on our results, we suggest that further chemical and clinical studies of ceftriaxone sodium brands are warranted and recommend that physicians consider alternative cost-effective generic brands in patient prescriptions. PMID- 26868367 TI - Not the End of the Odyssey: Parental Perceptions of Whole Exome Sequencing (WES) in Pediatric Undiagnosed Disorders. AB - Due to the lack of empirical information on parental perceptions of primary results of whole exome sequencing (WES), we conducted a retrospective semi structured interview with 19 parents of children who had undergone WES. Perceptions explored during the interview included factors that would contribute to parental empowerment such as: parental expectations, understanding of the WES and results, utilization of the WES information, and communication of findings to health/educational professionals and family members. Results of the WES had previously been communicated to families within a novel framework of clinical diagnostic categories: 5/19 had Definite diagnoses, 6/19 had Likely diagnoses, 3/19 had Possible diagnosis and 5/19 had No diagnosis. All parents interviewed expressed a sense of duty to pursue the WES in search of a diagnosis; however, their expectations were tempered by previous experiences with negative genetic testing results. Approximately half the parents worried that a primary diagnosis that would be lethal might be identified; however, the hope of a diagnosis outweighed this concern. Parents were accurately able to summarize their child's WES findings, understood the implications for recurrence risks, and were able to communicate these findings to family and medical/educational providers. The majority of those with a Definite/Likely diagnosis felt that their child's medical care was more focused, or there was a reduction in worry, despite the lack of a specific treatment. Irrespective of diagnostic outcome, parents recommended that follow-up visits be built into the process. Several parents expressed a desire to have all variants of unknown significance (VUS) reported to them so that they could investigate these themselves. Finally, for some families whose children had a Definite/Likely diagnosis, there was remaining frustration and a sense of isolation, due to the limited information that was available about the diagnosed rare disorders and the inability to connect to other families, suggesting that for families with rare genetic disorders, the diagnostic odyssey does not necessarily end with a diagnosis. Qualitative interviewing served a meaningful role in eliciting new information about parental motivations, expectations, and knowledge of WES. Our findings highlight a need for continued communication with families as we navigate the new landscape of genomic sequencing. PMID- 26868368 TI - Slipping through the net: the paradox of nursing's electronic theses and dissertations. AB - AIM: The study's main aim was to gain in-depth understanding of how nurse scholars engage with electronic theses and dissertations. Through elicitation of opinions about challenges and opportunities, and perceptions of future development, the study also aimed to influence the design of a new international web-based forum for learning and sharing information on this topic. BACKGROUND: Electronic theses and dissertations provide an opportunity to radically change the way in which graduate student research is presented, disseminated and used internationally. However, as revealed by a multi-national survey in 2011, many nurse scholars in vanguard universities have little awareness of how to find and exploit this ever-expanding global knowledge resource that is increasingly available free in full text format. Within this context more detailed understandings of nurse scholars' thinking and actions are required. METHODS: A qualitative approach using a semi-structured interview guide was utilized to elicit perceptions from 14 nurse scholars. RESULTS: Thematic analysis of the interviewees' responses identified six major themes: initial exposure and effect; searching; accessing; handling; using; and evaluation. Insights were gained about the value of these resources and behaviours in using them as exemplars for structure, format and methodology. CONCLUSION AND IMPLICATIONS FOR NURSING AND NURSING POLICY: Despite the small study size, the findings added valuable new insights to the overview gained from the 2011 survey. These have been used to inform development of a new global initiative: the International Network for Electronic Theses and Dissertations in Nursing. Featuring an educational website (www.inetdin.net), this initiative aims to support and challenge nursing's policy makers, practitioners and especially educators to utilize this neglected but exponentially increasing wellspring of international nursing knowledge. PMID- 26868366 TI - Cellular and molecular aspects of pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that affects nearly 50,000 patients each year. The overall 5-year survival rate for this malignancy remains the lowest of any cancer at around 7% due to limited diagnostic methods, disease aggressiveness and a lack of targeted therapeutic interventions. This review highlights the successes achieved over the past several decades as well as the significant cellular and molecular hurdles that remain in combatting this deadly disease at a translational level. PMID- 26868369 TI - Simulation of various randomization strategies for a clinical trial in sickle cell disease. AB - OBJECTIVE: To use numerical simulation to evaluate various randomization strategies for a clinical trial in sickle cell disease (SCD). METHODS: The Inhaled Mometasone to Promote Reduction in Vaso-occlusive Events trial* is a randomized, controlled, feasibility study of inhaled mometasone for individuals with SCD who do not have asthma. The target sample size is 45 patients and one goal is to limit imbalance with respect to two important covariates (1) hydroxyurea use and (2) historical emergency department (ED) utilization. We compared three methods of patient allocation (simple randomization, block randomization, and biased-coin adaptive randomization) using numerical simulation (10 000 trials). The primary outcome measure was the proportion of simulated trials with numerically apparent differences in the two covariates: hydroxyurea use (binary) and ED utilization (three-level ordinal). RESULTS: Overall, only 1.6% of simulated trials had any covariate comparison with P < 0.3 across groups for simple randomization, and 0% for both the block and adaptive randomization. In trials where the total sample size was 45 patients, the block randomization strategy achieved the greatest balance because participants were deterministically assigned to the treatment arm that balanced covariates. The adaptive strategy achieved similar results without deterministic treatment assignments even when trials included only 45 patients. DISCUSSION: Adaptive clinical trial designs have potential to mitigate some of the challenges that have hampered SCD trials. In small exploratory trials, even non-statistically significant differences in important covariates can threaten interpretability and external validity. CONCLUSION: Adaptive randomization performed similarly to block randomization and offers advantages including better allocation concealment and less ability for investigators to predict the next assignment. PMID- 26868370 TI - The ion microscope as a tool for quantitative measurements in the extreme ultraviolet. AB - We demonstrate a tool for quantitative measurements in the extreme ultraviolet (EUV) spectral region measuring spatially resolved atomic ionization products at the focus of an EUV beam. The ionizing radiation is a comb of the 11(th)-15(th) harmonics of a Ti:Sapphire femtosecond laser beam produced in a Xenon gas jet. The spatial ion distribution at the focus of the harmonics is recorded using an ion microscope. Spatially resolved single- and two-photon ionization products of Argon and Helium are observed. From such ion distributions single- and two-photon generalized cross sections can be extracted by a self-calibrating method. The observation of spatially resolved two-EUV-photon ionization constitutes an initial step towards future single-shot temporal characterization of attosecond pulses. PMID- 26868371 TI - A benchmark study on error-correction by read-pairing and tag-clustering in amplicon-based deep sequencing. AB - BACKGROUND: The high error rate of next generation sequencing (NGS) restricts some of its applications, such as monitoring virus mutations and detecting rare mutations in tumors. There are two commonly employed sequencing library preparation strategies to improve sequencing accuracy by correcting sequencing errors: read-pairing method and tag-clustering method (i.e. primer ID or UID). Here, we constructed a homogeneous library from a single clone, and compared the variant calling accuracy of these error-correction methods. RESULT: We comprehensively described the strengths and pitfalls of these methods. We found that both read-pairing and tag-clustering methods significantly decreased sequencing error rate. While the read-pairing method was more effective than the tag-clustering method at correcting insertion and deletion errors, it was not as effective as the tag-clustering method at correcting substitution errors. In addition, we observed that when the read quality was poor, the tag-clustering method led to huge coverage loss. We also tested the effect of applying quality score filtering to the error-correction methods and demonstrated that quality score filtering was able to impose a minor, yet statistically significant improvement to the error-correction methods tested in this study. CONCLUSION: Our study provides a benchmark for researchers to select suitable error-correction methods based on the goal of the experiment by balancing the trade-off between sequencing cost (i.e. sequencing coverage requirement) and detection sensitivity. PMID- 26868372 TI - [18F]fluorodeoxyglucose positron emission tomography/computed tomography and trophoblastic disease: the gynecologist perspective. AB - INTRODUCTION: Gestational trophoblastic disease (GTD) is a group of different pregnancy-related diseases that includes hydatidiform mole (HM), invasive mole, gestational choriocarcinoma (CC), placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). The potential role of 18F-2-fluoro-2-deoxy D-glucose ([18F]FDG) positron emission tomography (PET) in diagnostic setting and follow up phase of GTD is still largely debated. EVIDENCE ACQUISITION: The aim of this review is to examine the role of [18F]FDG PET/computed tomography (CT) in diagnosis, treatment and follow up of different disease subtypes. A systematic computerized search of the literature, from 1996 until December 2015 was performed in PubMed and MEDLINE to identify relevant papers to be included for this purpose. All pertinent articles and their reference lists were systematically reviewed in order to identify other studies for potential inclusion. EVIDENCE SYNTHESIS: Regarding HM a potential prognostic relevance of maximum standardized uptake value (SUV max) of molar tissue within the uterus before evacuation has been suggested. Considering CC staging, most [18F]FDG PET evaluations confirmed the results of conventional imaging. However [18F]FDG PET played a key role in discriminating ambiguous lesions on routine imaging work-up. [18F]FDG PET was particularly useful in evaluating disease recurrence and chemo resistance, thanks to the possibility of an early identification of the active tumor site. Since the main treatment of PSTT is surgery, the contribution of [18F]FDG PET in differential diagnosis and in providing a more precise mapping of resectable metastasis or the complete response to treatment is advisable. CONCLUSIONS: Since the role of [18F]FDG PET and PET/CT in diagnostic setting and follow up of GTN is still controversial, further studies are required to clarify this issue. PMID- 26868374 TI - Resolution of Cutaneous Sarcoidosis Following Topical Application of Ganoderma lucidum (Reishi Mushroom). AB - Ganoderma lucidum (reishi mushroom) has been used in traditional Chinese and Japanese medicine as a herbal remedy for over 2000 years. Studies have shown that G. lucidum has anti-allergic, anti-oxidant, anti-tumor, anti-viral, and anti inflammatory properties. A review of the literature revealed that there were no studies examining the use of G. lucidum for the treatment of skin diseases. Here, we report the case of a 44-year-old male patient who used soap enriched with G. lucidum and goat's milk for 3 days in treating annular cutaneous sarcoidosis. The patient showed almost complete regression of the lesions. PMID- 26868373 TI - Empirical evidence for large X-effects in animals with undifferentiated sex chromosomes. AB - Reproductive isolation is crucial for the process of speciation to progress. Sex chromosomes have been assigned a key role in driving reproductive isolation but empirical evidence from natural population processes has been restricted to organisms with degenerated sex chromosomes such as mammals and birds. Here we report restricted introgression at sex-linked compared to autosomal markers in a hybrid zone between two incipient species of European tree frog, Hyla arborea and H. orientalis, whose homologous X and Y sex chromosomes are undifferentiated. This large X-effect cannot result from the dominance or faster-X aspects of Haldane's rule, which are specific to degenerated sex chromosomes, but rather supports a role for faster-heterogametic-sex or faster-male evolutionary processes. Our data suggest a prominent contribution of undifferentiated sex chromosomes to speciation. PMID- 26868376 TI - Spontaneous resolution of foveal detachment in traction maculopathy in high myopia unrelated to posterior vitreous detachment. AB - BACKGROUND: Foveal detachment associated with foveoschisis usually takes a progressive course, and is associated with a poor visual outcome. The purpose of this study was to report the spontaneous resolution of foveal detachment in patients with myopic traction maculopathy without posterior vitreous detachment. METHODS: A retrospective study involving eight cases of high myopia with foveoschisis and foveal detachment in which the subfoveal fluid had spontaneously resolved. The clinical characteristics and optical coherence tomography (OCT) findings were described. RESULTS: All cases involved predominant schisis in the outer retina, with six showing internal limiting membrane detachment. The average central foveal thickness was 445.1 MUm, and the average foveal detachment height was 271.5 MUm. None of the cases involved traction of the vitreomacular interface or posterior vitreous detachment (PVD), either before or after the resolution of foveal detachment. In seven cases, the mean best-corrected visual acuity improved after foveal reattachment. CONCLUSIONS: Spontaneous reattachment not associated with PVD can occur in cases of high myopic traction maculopathy, especially in those without obvious vitreomacular traction. PMID- 26868378 TI - Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? AB - BACKGROUND: Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. METHODS: Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. RESULTS: VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. CONCLUSIONS: Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition. PMID- 26868381 TI - Draft Genome Sequences of Two Methicillin-Resistant Clinical Staphylococcus aureus Isolates. AB - Here, we report the draft genome sequences of two methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, hospital-associated perirectal isolate 32S (ST 239) from a colitis tracheostomy patient and community-associated MRSA isolate 42S (ST 772) from a hepatic-splenomegaly patient in Rawalpindi, Pakistan. PMID- 26868382 TI - Complete Genome Sequences of Dengue Virus Type 1 to 4 Strains Used for the Development of CBER/FDA RNA Reference Reagents and WHO International Standard Candidates for Nucleic Acid Testing. AB - Dengue virus (DENV), a member of the Flaviviridae family, is the most common and clinically significant arbovirus in the world and is endemic in more than 100 countries. Here, we report the complete sequences of four DENV serotypes used in the development of the CBER/FDA RNA reference reagents and WHO International Standard candidates for nucleic acid testing. PMID- 26868380 TI - Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, In Vitro Evaluation, and Ex Vivo Assessment. AB - Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2-4% w/v and 0-40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 MUg cm-2 drug retention in the skin, 44.312 MUg cm-2 h-1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation. PMID- 26868379 TI - A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology. AB - Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 * 10(-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology. PMID- 26868383 TI - Draft Genome Sequence of the Fish Pathogen Mycobacterium pseudoshottsii Strain JCM15466, a Species Closely Related to M. marinum. AB - Mycobacterium pseudoshottsii is a slowly growing photochromogenic mycobacterium and fish pathogen isolated from wild marine fishes. M. pseudoshottsii closely resembles M. marinum, which is a human and animal pathogen. Here, we report the draft genome sequence of M. pseudoshottsii strain JCM15466, originally isolated from striped bass, Morone saxatilis. PMID- 26868384 TI - Draft Genome Sequence of the Radioresistant Bacterium Deinococcus grandis, Isolated from Freshwater Fish in Japan. AB - Deinococcus grandis is a radioresistant bacterium isolated from freshwater fish in Japan. Here we reported the draft genome sequence of D. grandis (4.1 Mb), which will be useful for elucidating the common principles of radioresistance in Deinococcus species through the comparative analysis of genomic sequences. PMID- 26868385 TI - Draft Genome Sequences of Enterohemorrhagic Escherichia coli Encoding Extended Spectrum Beta-Lactamases. AB - Extended-spectrum beta-lactamases (ESBLs) have rarely been observed among Shiga toxigenic Escherichia coli (STEC), and, to our best knowledge, only three ESBL positive isolates of the enterohemorrhagic E. coli (EHEC) subpathotype have been reported. Here, we present the first draft genome sequences of two ESBL-positive EHEC isolates belonging to serotypes O111:H8 and O151:H16. PMID- 26868386 TI - Draft Genome Sequence of a Klebsiella pneumoniae Carbapenemase-Positive Sequence Type 111 Pseudomonas aeruginosa Strain. AB - Here, we report the draft genome sequence of a sequence type 111 Pseudomonas aeruginosa strain isolated in 2014 from a patient at the NIH Clinical Center. This P. aeruginosa strain exhibits pan-drug resistance and harbors the blaKPC-2 gene, encoding the Klebsiella pneumoniae carbapenemase enzyme, on a plasmid. PMID- 26868387 TI - Complete Coding Sequences of Three Toscana Virus Strains Isolated from Sandflies in France. AB - Toscana virus (TOSV) is an arthropod-borne virus belonging to the sandfly fever Naples virus species within the genus Phlebovirus. We report here the complete coding sequences of three TOSV strains belonging to lineage B and isolated from sandflies trapped in the Southeast of France between 2009 and 2013. PMID- 26868388 TI - Complete Genome Sequencing of Dengue Virus Type I from Zhuhai City, China. AB - The detection and successful typing of dengue virus (DENV) from patients with suspected dengue fever are important for stopping outbreaks and preventing the recurrence of this virus. In this study, we reported complete genomic sequences of DENV-1 isolated from Zhuhai patients, providing basic information for future epidemic dengue disease detection. PMID- 26868389 TI - Draft Genome Sequence of Desulfitobacterium hafniense Strain DH, a Sulfate Reducing Bacterium Isolated from Paddy Soils. AB - Desulfitobacterium hafniense strain DH is a sulfate-reducing species. Here, we report the draft genome sequence of strain DH, with a size of 5,368,588 bp, average G+C content of 47.48%, and 5,296 predicted protein-coding sequences. PMID- 26868390 TI - Six Pseudoalteromonas Strains Isolated from Surface Waters of Kabeltonne, Offshore Helgoland, North Sea. AB - Draft genomes are presented for 6 Pseudoalteromonas sp. strains isolated from surface waters at Kabeltonne, Helgoland, a long-term ecological research station in the North Sea. These strains contribute knowledge of the genomic underpinnings of a developing model system to study phage-host dynamics of a particle associated ocean copiotroph. PMID- 26868391 TI - Complete Genome Sequence of Lactobacillus acidophilus MN-BM-F01. AB - Lactobacillus acidophilus MN-BM-F01 was originally isolated from a traditional fermented dairy product in China. The characteristics of this bacterium are its low post-acidification ability and high acid-producing rate. Here, we report the main genome features of L. acidophilus MN-BM-F01. PMID- 26868392 TI - Draft Genome Sequence of Hymenobacter sp. Strain AT01-02, Isolated from a Surface Soil Sample in the Atacama Desert, Chile. AB - Here, we report the 5.09-Mb draft genome sequence of Hymenobacter sp. strain AT01 02, which was isolated from a surface soil sample in the Atacama Desert, Chile. The isolate is extremely resistant to UV-C radiation and is able to accumulate high intracellular levels of Mn/Fe. PMID- 26868393 TI - Draft Genome Sequence of Proteus mirabilis NO-051/03, Representative of a Multidrug-Resistant Clone Spreading in Europe and Expressing the CMY-16 AmpC-Type beta-Lactamase. AB - Proteus mirabilis NO-051/03, representative of a multidrug-resistant clone expressing the CMY-16 AmpC-type beta-lactamase and circulating in Europe since 2003, was sequenced by a MiSeq platform using a paired-end approach. The genome was assembled in 100 scaffolds with a total length of 4,197,318 bp. Analysis of the draft genome sequence revealed the presence of several acquired resistance determinants to beta-lactams, aminoglycosides, phenicols, tetracyclines, trimethoprim, and sulfonamides, of one plasmid replicon, and of a type I-E clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (Cas) adaptive immune system. PMID- 26868394 TI - Draft Genome Sequence of a Versatile Hydrocarbon-Degrading Bacterium, Rhodococcus pyridinivorans Strain KG-16, Collected from Oil Fields in India. AB - We describe here a 5.8-Mb draft genome sequence of Rhodococcus pyridinivorans strain KG-16, which was obtained from the soil samples collected from the oilfields of Krishna-Godavari basin in India. This genomic resource can provide insights into the pathways and mechanisms of hydrocarbon degradation and potentially aid in bioremediation applications. PMID- 26868395 TI - Draft Genome Sequences of Two Strains of Xanthomonas arboricola pv. celebensis Isolated from Banana Plants. AB - We report here the annotated draft genome sequences of strains Xanthomonas arboricola pv. celebensis NCPPB 1832 and NCPPB 1630 (NCPPB, National Collection of Plant Pathogenic Bacteria), both isolated from Musa species in New Zealand. This will allow the comparison of genomes between phylogenetically distant xanthomonads that have independently converged with the ability to colonize banana plants. PMID- 26868396 TI - Draft Genome Sequence of Enterococcus faecium Strain 58m, Isolated from Intestinal Tract Content of a Woolly Mammoth, Mammuthus primigenius. AB - Enterococcus faecium 58m is a putative ancient nonpathogenic strain isolated from the intestinal content of an adult woolly mammoth (Mammuthus primigenius). Here, we report its draft genome sequence, consisting of 60 contigs. In silico genomic analysis was performed to determine the genetic features and pathogenic potential of this microorganism. PMID- 26868397 TI - Draft Genome Sequence of Sphingomonas sp. WG, a Welan Gum-Producing Strain. AB - We report the draft genome sequence of Sphingomonas sp. WG, a high welan gum producing strain with a yield of 33 g/L. The core of wel cluster for welan gum biosynthesis contained 24 coding sequences in the genome, which will provide the genetic information on welan gum production. PMID- 26868398 TI - Draft Genome Sequence of Uncultured SAR324 Bacterium lautmerah10, Binned from a Red Sea Metagenome. AB - A draft genome of SAR324 bacterium lautmerah10 was assembled from a metagenome of a surface water sample from the Red Sea, Saudi Arabia. The genome is more complete and has a higher G+C content than that of previously sequenced SAR324 representatives. Its genomic information shows a versatile metabolism that confers an advantage to SAR324, which is reflected in its distribution throughout different depths of the marine water column. PMID- 26868399 TI - Draft Genome Sequence of the Syntrophic Lactate-Degrading Bacterium Tepidanaerobacter syntrophicus JLT. AB - We report here a high-quality draft genome sequence of the type strain (JL) of Tepidanaerobacter syntrophicus, an obligately anaerobic and moderately thermophilic bacterium, which is able to perform syntrophic lactate degradation with hydrogenotrophic methanogens. The genome comprises 2.43 Mb in 9 scaffolds, with a G+C content of 38.6%. PMID- 26868400 TI - Draft Genome Sequences of the Turfgrass Pathogen Sclerotinia homoeocarpa. AB - Sclerotinia homoeocarpa (F. T. Bennett) is one of the most economically important pathogens on high-amenity cool-season turfgrasses, where it causes dollar spot. To understand the genetic mechanisms of fungicide resistance, which has become highly prevalent, the whole genomes of two isolates with varied resistance levels to fungicides were sequenced. PMID- 26868401 TI - Complete Genome Sequences of Two Interactive Moderate Thermophiles, Paenibacillus napthalenovorans 32O-Y and Paenibacillus sp. 32O-W. AB - Microorganisms with the capability to desulfurize petroleum are in high demand with escalating restrictions currently placed on fuel purity. Thermophilic desulfurizers are particularly valuable in high-temperature industrial applications. We report the whole-genome sequences of Paenibacillus napthalenovorans 32O-Y and Paenibacillus sp. 32O-W, which can and cannot, respectively, metabolize dibenzothiophene. PMID- 26868402 TI - Genome Sequence of Selenium-Solubilizing Bacterium Caulobacter vibrioides T5M6. AB - Caulobacter vibrioides T5M6 is a Gram-negative strain that strongly solubilizes selenium (Se) mineral into Se(IV) and was isolated from a selenium mining area in Enshi, southwest China. This strain produces the phytohormone IAA and promotes plant growth. Here we present the genome of this strain containing a large number of genes encoding resistances to copper and antibiotics. PMID- 26868403 TI - Draft Genome Sequence of Pseudomonas syringae pv. syringae ALF3 Isolated from Alfalfa. AB - We report here the annotated draft genome sequence of Pseudomonas syringae pv. syringae strain ALF3, isolated in Wyoming. A comparison of this genome sequence with those of closely related strains of P. syringae adapted to other hosts will facilitate research into interactions between this pathogen and alfalfa. PMID- 26868404 TI - Draft Genome Sequence of Cylindrospermopsis sp. Strain CR12 Extracted from the Minimetagenome of a Nonaxenic Unialgal Culture from a Tropical Freshwater Lake. AB - Cylindrospermopsis is known to be one of the major bloom-forming cyanobacterial genera in many freshwater environments. We report here the draft genome sequence of a tropical Cylindrospermopsis sp. strain, CR12, which is capable of producing the hepatotoxic cylindrospermopsin. PMID- 26868405 TI - Draft Genome Sequence of Vibrio sp. Strain Evh12, a Bacterium Retrieved from the Gorgonian Coral Eunicella verrucosa. AB - To shed light on the associations established between Vibrio species and soft corals in coastal ecosystems, we report here the draft genome sequence of Vibrio sp. strain Evh12, a bacterium that has been isolated from the gorgonian coral Eunicella verrucosa and that shows antagonistic activity against Escherichia coli. PMID- 26868406 TI - Complete Genome Sequence of the African Strain AXO1947 of Xanthomonas oryzae pv. oryzae. AB - Xanthomonas oryzae pv. oryzae is the etiological agent of bacterial rice blight. Three distinct clades of X. oryzae pv. oryzae are known. We present the complete annotated genome of the African clade strain AXO194 using long-read single molecule PacBio sequencing technology. The genome comprises a single chromosome of 4,674,975 bp and encodes for nine transcriptional activator-like (TAL) effectors. The approach and data presented in this announcement provide information for complex bacterial genome organization and the discovery of new virulence effectors, and they facilitate target characterization of TAL effectors. PMID- 26868407 TI - Draft Genome Sequence of Mycobacterium tuberculosis KT-0133, Isolated in South Korea. AB - Here, we present the draft genome sequence of Mycobacterium tuberculosis KT-0133, which belongs to the Korean-Beijing family. This sequence will provide a new perspective on the evolution and accommodation of M. tuberculosis KT-0133 in human hosts. PMID- 26868408 TI - Draft Genome Sequence of Pseudomonas sp. Strain ADP, a Bacterial Model for Studying the Degradation of the Herbicide Atrazine. AB - We report here the 7,259,392-bp draft genome of Pseudomonas sp. strain ADP. This is a bacterial strain that was first isolated in the 1990s from soil for its ability to mineralize the herbicide atrazine. It has extensively been studied as a model to understand the atrazine biodegradation pathway. This genome will be used as a reference and compared to evolved populations obtained by experimental evolution conducted on this strain under atrazine selection pressure. PMID- 26868409 TI - Draft Genome Sequence of Bacillus methylotrophicus FKM10, a Plant Growth Promoting Rhizobacterium Isolated from Apple Rhizosphere. AB - Bacillus methylotrophicus FKM10 is a strain of plant growth-promoting rhizobacterium with antimicrobial activity, which was isolated from apple rhizosphere. Here, we present the genome sequence of B. methylotrophicus FKM10. Two scaffolds were finally assembled, and several functional genes related to its antimicrobial activity were discovered. PMID- 26868410 TI - Genome Sequence of Bacillus pumilus Strain Bonn, Isolated from an Anthrax-Like Necrotic Skin Infection Site of a Child. AB - We report the draft genome sequence of Bacillus pumilus strain Bonn associated with human skin infection. B. pumilus Bonn was isolated from a carbuncle-like necrotic site, resembling cutaneous anthrax, on the back of the hand of a 10-year old child. PMID- 26868411 TI - Correction for Hansen et al., Draft Genome Sequence of a Taxonomically Unique Neisseria Strain Isolated from a Greater White-Fronted Goose (Anser albifrons) Egg on the North Slope of Alaska. PMID- 26868412 TI - Facing the Unknown: Intolerance of Uncertainty in Children with Autism Spectrum Disorder. AB - BACKGROUND: Anxiety is a common problem for children with autism spectrum disorder (ASD). Recent research indicates that intolerance of uncertainty (IU) may be an important aspect of anxiety for this population. IU is the belief that uncertainty is upsetting, and not knowing what is going to happen is negative. There is little known about the phenomenology of IU in children with ASD. We therefore present data from parent focus groups exploring this concept in children with ASD. METHODS: Participants were asked to differentiate IU from dislike of change and fear, and to discuss examples of IU and the strategies they use to manage it. Their experiences of IU and strategies are presented. RESULTS: IU was evident across novel and familiar situations and parents used a variety of strategies to manage IU. Their experiences of IU and strategies used are presented. CONCLUSIONS: Participants were able to identify and provide examples of IU suggesting that it is a recognizable construct among children with ASD. PMID- 26868414 TI - Research bodies vow to share data on Zika. PMID- 26868413 TI - Ancestral reconstruction of tick lineages. AB - Ancestral reconstruction in its fullest sense aims to describe the complete evolutionary history of a lineage. This depends on accurate phylogenies and an understanding of the key characters of each parental lineage. An attempt is made to delineate our current knowledge with regard to the ancestral reconstruction of the tick (Ixodida) lineage. Tick characters may be assigned to Core of Life, Lineages of Life or Edges of Life phenomena depending on how far back these characters may be assigned in the evolutionary Tree of Life. These include housekeeping genes, sub-cellular systems, heme processing (Core of Life), development, moulting, appendages, nervous and organ systems, homeostasis, respiration (Lineages of Life), specific adaptations to a blood-feeding lifestyle, including the complexities of salivary gland secretions and tick-host interactions (Edges of Life). The phylogenetic relationships of lineages, their origins and importance in ancestral reconstruction are discussed. Uncertainties with respect to systematic relationships, ancestral reconstruction and the challenges faced in comparative transcriptomics (next-generation sequencing approaches) are highlighted. While almost 150 years of information regarding tick biology have been assembled, progress in recent years indicates that we are in the infancy of understanding tick evolution. Even so, broad reconstructions can be made with relation to biological features associated with various lineages. Conservation of characters shared with sister and parent lineages are evident, but appreciable differences are present in the tick lineage indicating modification with descent, as expected for Darwinian evolutionary theory. Many of these differences can be related to the hematophagous lifestyle of ticks. PMID- 26868415 TI - Contingency, convergence and hyper-astronomical numbers in biological evolution. AB - Counterfactual questions such as "what would happen if you re-run the tape of life?" turn on the nature of the landscape of biological possibilities. Since the number of potential sequences that store genetic information grows exponentially with length, genetic possibility spaces can be so unimaginably vast that commentators frequently reach of hyper-astronomical metaphors that compare their size to that of the universe. Re-run the tape of life and the likelihood of encountering the same sequences in such hyper-astronomically large spaces is infinitesimally small, suggesting that evolutionary outcomes are highly contingent. On the other hand, the wide-spread occurrence of evolutionary convergence implies that similar phenotypes can be found again with relative ease. How can this be? Part of the solution to this conundrum must lie in the manner that genotypes map to phenotypes. By studying simple genotype-phenotype maps, where the counterfactual space of all possible phenotypes can be enumerated, it is shown that strong bias in the arrival of variation may explain why certain phenotypes are (repeatedly) observed in nature, while others never appear. This biased variation provides a non-selective cause for certain types of convergence. It illustrates how the role of randomness and contingency may differ significantly between genetic and phenotype spaces. PMID- 26868416 TI - Patient safety and patient assessment in pre-hospital care: a study protocol. AB - BACKGROUND: Patient safety issues in pre-hospital care are poorly investigated. The aim of the planned study is to survey patient safety problems in pre-hospital care in Sweden. METHODS/DESIGN: The study is a retro-perspective structured medical record review based on the use of 11 screening criteria. Two instruments for structured medical record review are used: a trigger tool instrument designed for pre-hospital care and a newly development instrument designed to compare the pre-hospital assessment with the final hospital assessment. Three different ambulance organisations are participating in the study. Every month, one rater in each organisation randomly collects 30 medical records for review. With guidance from the review instrument, he/she independently reviews the record. Every month, the review team meet for a discussion of problematic reviews. The results will be analysed with descriptive statistics and logistic regression. DISCUSSION: The findings will make an important contribution to knowledge about patient safety issues in pre-hospital care. PMID- 26868417 TI - Sublethal Effects of Essential Oils From Eucalyptus staigeriana (Myrtales: Myrtaceae), Ocimum gratissimum (Lamiales: Laminaceae), and Foeniculum vulgare (Apiales: Apiaceae) on the Biology of Spodoptera frugiperda (Lepidoptera: Noctuidae). AB - Spodoptera frugiperda (Smith 1797) (Lepidoptera: Noctuidae) is a major pest of maize, Zea mays L. Its control is often achieved through repeated applications per season of insecticides, which may lead to adverse effects on the ecosystem. Thus, the study of alternative methods with less environmental impact has expanded to include the use of essential oils. These oils are products of the secondary metabolism in plants, and their insecticidal activity has been widely demonstrated in populations of many pest insects. This study evaluated the insecticidal activities of essential oils from Eucalyptus staigeriana, Ocimum gratissimum, and Foeniculum vulgare on Spodoptera frugiperda. Gas chromatography mass spectrometry profiles and contact toxicity of these oils as well as their sublethal effects on larvae and reproductive parameters in adults were evaluated. All three oils had sublethal effects on S. frugiperda; however, the oil of O. gratissimum showed the best results at all doses tested. These essential oils may have promise for control of S. frugiperda. PMID- 26868418 TI - Seroprevalence of antibodies against GII.4 norovirus among children in Pune, India. AB - This study reports the seroprevalence of antibodies against GII.4 norovirus among children (<=5 years) in Pune, India. Of 191 serum specimens, 98 (51.3%) tested positive with 61, 34 and 3 having IgG, IgG-IgA and IgG-IgA-IgM, respectively. Histoblood group antigen (HBGA)-blocking antibodies were detected in 33 of the 54 tested positive specimens. IgG and blocking antibody prevalence and titer varied with age and was lowest among children aged 6-23 months. Antibody-positive children, suggesting past norovirus exposure, showed significantly lower faecal norovirus RNA detection rate than antibody-negative children. Further investigation of the seroepidemiology of norovirus infections in India is warranted. J. Med. Virol. 88:1636-1640, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26868419 TI - The feasibility of transpedicular screw fixation of the subaxial cervical spine in the Arab population: a computed tomography-based morphometric study. AB - BACKGROUND: Transpedicular screw fixation of the cervical spine provides excellent biomechanical stability. The feasibility of inserting a 3.5-mm screw in the pedicle requires a minimum pedicle diameter of 4.5 mm. This diameter allows at least 0.5 mm bony bridge medially and laterally in order to avoid pedicle violation which can result in neurovascular complications. We aim to evaluate the feasibility of this technique in Arab people since no data are available about this population. MATERIALS AND METHODS: This cross-sectional study involved a retrospective review of computed tomography scans of normal cervical spines of 99 Arab adults. Ten morphometric measurements were obtained. Data were analyzed using a p value of <=0.05 as the cut-off level of statistical significance. RESULTS: Our sample included 63 (63.6 %) males and 36 (36.4 %) females, with a mean age of 35.5 +/- 16.5 years. The morphometric parameters of C3-C7 spine pedicles were larger in males than in females. The outer pedicle width (OPW) was <4.5 mm in >25 % of all subjects at C3-C6 vertebrae. Statistically significant differences in the OPW between males and females were noted at C3 (p = 0.032) and C6 (p = 0.004). CONCLUSIONS: Inserting pedicle screws in the subaxial cervical spine is feasible among the majority of Arab people. LEVEL OF EVIDENCE: Level 3. PMID- 26868420 TI - Trunnionosis in total hip arthroplasty: a review. AB - Trunnionosis is defined as wear of the femoral head-neck interface and has recently been acknowledged as a growing cause of total hip arthroplasty failure. Some studies have reported that it accounts for up to 3 % of all revisions. The exact cause of trunnionosis is currently unknown; however, postulated etiologies include modular junction wear, corrosion damage, and metal ion release. Additionally, implant design and trunnion geometries may contribute to the progression of component failure. In order to aid in our understanding of this phenomenon, our aim was to present the current literature on (1) the effect of femoral head size on trunnionosis, (2) the effect of trunnion design on trunnionosis, (3) localized biological reactions associated with trunnionosis, and (4) gross trunnion failures. It is hoped that this will encourage further research and interest aimed at minimizing this complication. PMID- 26868421 TI - Effect of Radiation on the Electrical Properties of PEDOT-Based Nanocomposites. AB - Systematic evaluation of the influence of radiation on the electrical response of hybrid nanocomposites obtained by adding multi-walled carbon nanotubes into poly(3,4-ethylenedioxythiophene) and poly(styrenesulfonate) host matrix is presented. Variations of resistance and conductivity of nanocomposites depending on the volume fraction of nanotubes in the matrix, ionizing radiation dosage, and temperature are analyzed. PMID- 26868422 TI - Indocyanine Green Loaded Reduced Graphene Oxide for In Vivo Photoacoustic/Fluorescence Dual-Modality Tumor Imaging. AB - Multimodality imaging based on multifunctional nanocomposites holds great promise to fundamentally augment the capability of biomedical imaging. Specifically, photoacoustic and fluorescence dual-modality imaging is gaining much interest because of their non-invasiveness and the complementary nature of the two modalities in terms of imaging resolution, depth, sensitivity, and speed. Herein, using a green and facile method, we synthesize indocyanine green (ICG) loaded, polyethylene glycol (PEG)ylated, reduced nano-graphene oxide nanocomposite (rNGO PEG/ICG) as a new type of fluorescence and photoacoustic dual-modality imaging contrast. The nanocomposite is shown to have minimal toxicity and excellent photoacoustic/fluorescence signals both in vitro and in vivo. Compared with free ICG, the nanocomposite is demonstrated to possess greater stability, longer blood circulation time, and superior passive tumor targeting capability. In vivo study shows that the circulation time of rNGO-PEG/ICG in the mouse body can sustain up to 6 h upon intravenous injection; while after 1 day, no obvious accumulation of rNGO-PEG/ICG is found in any major organs except the tumor regions. The demonstrated high fluorescence/photoacoustic dual contrasts, together with its low toxicity and excellent circulation life time, suggest that the synthesized rNGO-PEG/ICG can be a promising candidate for further translational studies on both the early diagnosis and image-guided therapy/surgery of cancer. PMID- 26868424 TI - Radiographic Landmarks for Identifying the Anterolateral Ligament of the Knee. AB - PURPOSE: To identify the radiographic position of the origin and insertion of the anterolateral ligament (ALL) of the knee on a lateral radiograph. METHODS: Twelve unpaired, fresh-frozen cadaveric knees were dissected to expose the ALL. The origin and insertion of the ALL on each cadaver were then tagged using 2-mm radiopaque beads. True lateral fluoroscopic views of the knee were then obtained, and the distance from known radiographic landmarks was recorded by 2 reviewers. RESULTS: The origin of the ALL was found at a distance that is 37.0 +/- 9.2% of the total anterior-posterior length of the femoral condyle from the posterior edge as measured along Blumensaat's line. The insertion was located at a distance that is 56.1 +/- 6.9% of the total length of the tibial plateau from the posterior edge. The origin of the ALL is 5 mm posterior to a line from the posterior femoral cortex and 9 mm distal to a line along Blumensaat's line. The insertion is 4 mm anterior to the 50% mark of the anterior-posterior width of the tibia, 14 mm distal to the articular surface. CONCLUSIONS: The origin and insertion of the ALL can be accurately identified using intraoperative fluoroscopy. CLINICAL RELEVANCE: Determining radiographic parameters for the ALL will assist in developing accurate surgical techniques for ALL reconstruction. PMID- 26868423 TI - A Biotin Biosynthesis Gene Restricted to Helicobacter. AB - In most bacteria the last step in synthesis of the pimelate moiety of biotin is cleavage of the ester bond of pimeloyl-acyl carrier protein (ACP) methyl ester. The paradigm cleavage enzyme is Escherichia coli BioH which together with the BioC methyltransferase allows synthesis of the pimelate moiety by a modified fatty acid biosynthetic pathway. Analyses of the extant bacterial genomes showed that bioH is absent from many bioC-containing bacteria and is replaced by other genes. Helicobacter pylori lacks a gene encoding a homologue of the known pimeloyl-ACP methyl ester cleavage enzymes suggesting that it encodes a novel enzyme that cleaves this intermediate. We isolated the H. pylori gene encoding this enzyme, bioV, by complementation of an E. coli bioH deletion strain. Purified BioV cleaved the physiological substrate, pimeloyl-ACP methyl ester to pimeloyl-ACP by use of a catalytic triad, each member of which was essential for activity. The role of BioV in biotin biosynthesis was demonstrated using a reconstituted in vitro desthiobiotin synthesis system. BioV homologues seem the sole pimeloyl-ACP methyl ester esterase present in the Helicobacter species and their occurrence only in H. pylori and close relatives provide a target for development of drugs to specifically treat Helicobacter infections. PMID- 26868425 TI - Endoscopic Endonasal Approach to the Odontoid Pathologies. AB - BACKGROUND: Surgical anterior decompression represents the treatment of choice for symptomatic irreducible ventral craniovertebral junction (CVJ) compression. With the refinement of the endoscopic techniques, the endonasal route has been proposed as alternative to the classic transoral approach to CVJ. Some reports assess the effectiveness and safety of endoscopic endonasal approaches to CVJ pathologies. MATERIALS AND METHODS: From July 2011 to February 2014, 12 patients with symptomatic nonreducible ventral spinal cord compression underwent purely 3 dimensional endoscopic endonasal odontoidectomy in our department. The surgical technique is described. RESULTS: A good brainstem-medullary decompression was achieved in all patients. In 10 of 12 patients the endotracheal tube was removed just after the procedure with good recovery of the respiratory function. We report no cases of velopharyngeal insufficiency. In 5 of 12 patients the preservation of C1 anterior was achieved, without the need for posterior cervical fixation. DISCUSSION AND CONCLUSIONS: Endoscopic endonasal odontoidectomy has proven to be safe and effective in selected patients. Soft and hard palate preservation dramatically reduces the risk of postoperative velopharyngeal insufficiency. Moreover, the endonasal endoscopic approach provides a direct access to the dens. Three-dimensional high-definition endoscope, laser, and ultrasound bony curettes revealed to be useful tools for this approach that, however, remains a demanding one. PMID- 26868426 TI - Comparison of a Stand-Alone Anchored Spacer Versus Plate-Cage Construct in the Treatment of Two Noncontiguous Levels of Cervical Spondylosis: A Preliminary Investigation. AB - OBJECTIVE: The application of stand-alone anchored spacer (SAAS) in anterior cervical discectomy and fusion (ACDF) has been proven to be safe and effective to treat cervical spondylosis. Skip-level ACDF with SAAS, fusing only the involved levels without anterior plates, may be the optimal treatment. The aim of the study was to compare the clinical outcomes, radiologic results of SAAS, and plate cage construct in the treatment of 2 noncontiguous levels of cervical spondylosis. METHODS: A total of 65 patients with 2 noncontiguous levels of cervical spondylosis were included in the retrospective review of prospective collected data. The clinical and radiologic outcomes were assessed with the Japanese Orthopaedic Association score, Neck Disability Index, cervical alignment, and range of motion and disc height of intermediate segment, respectively. All the aforementioned parameters were compared before and after surgery in the respective group, which also were compared between the 2 groups. Complications also were recorded, and correlations between the surgical outcome and various factors were analyzed. RESULTS: No significant differences existed in clinical results between the 2 groups (P > 0.05). In addition, no statistical significance was observed in fusion rate, cervical alignment, and range of motion and disc height of intermediate segment, dysphagia, and hoarseness (P > 0.05). Preoperative Japanese Orthopaedic Association score and high-intensity signal in T2-weighted images were important predictors for surgical outcome. CONCLUSIONS: Skip-level ACDF with SAAS is a safe and effective treatment of 2 noncontiguous levels of cervical spondylosis without obvious contraindications, which can keep the IS intact, and have a low impact on the IS. PMID- 26868427 TI - 4'-O-beta-D-Glucosyl-5-O-Methylvisamminol, A Natural Histone H3 Phosphorylation Epigenetic Suppressor, Exerts a Neuroprotective Effect Through PI3K/Akt Signaling Pathway on Focal Cerebral Ischemia in Rats. AB - BACKGROUND: A bursting inflammation has been observed that compromises neurologic function in patients who experience stroke. We sought to examine the neuroprotective efficacy of 4'-O-beta-D-glucosyl-5-O-methylvisamminol (OGOMV), a novel histone H3 phosphorylation epigenetic suppressor) in a transient middle cerebral artery occlusion (tMCAO). METHODS: A rodent tMCAO model was used. Administration with 400 MUg/kg/day OGOMV was initiated 12 hours before (prevention) and 1 hour after animals were subjected to tMCAO (reversal). The cerebral cortex was harvested to examine protein kinase B (PI3D/Akt), 5-bromo-2' deoxyuridine (Western blot), and caspases (reverse-transcription polymerase chain reaction). In addition, cerebrospinal fluid samples were collected to examine interleukin 1-beta, interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-alpha (reverse-transcription polymerase chain reaction). RESULTS: Cortical 5-bromo-2'-deoxyuridine and phospho-PI3D/Akt were reduced in tMCAO animals, compared with the healthy controls but increased in the OGOMV treatment and prevention groups. Activated cortical caspase-3,-6, and -9a as well as increased IL-1beta and TNF-alpha levels were observed in the tMCAO animals (P < 0.05). Both prevention and treatment with OGOMV significantly reduced cleaved caspase-3 and -9a groups, but no significant change in caspase-6 was noted. Perifosine, an Akt inhibitor, was added to reduce the bioexpression of phospho P13D/Akt, and Bcl-2 level and increased cleaved caspase-9a level in both OGOMV prevention and treatment tMCAO groups (P > 0.05). CONCLUSION: Our study suggests that OGOMV could exert a neuroprotective effect by inhibiting the P13D/Akt protein, attenuating inflammation, and cleaved caspase-3- and -9a-related apoptosis. This study also lends credence to support the notion that the prevention of OGOMV could attenuate proinflammatory cytokine mRNA and late-onset caspases in tMCAO and merits further study. PMID- 26868428 TI - Recurrent Herpes Simplex Virus Encephalitis After Neurologic Surgery. AB - BACKGROUND: The herpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. Even with proper treatment, this infection is associated with a mortality rate of 19%-30% and with potential neurologic sequelae. Recurrences of encephalitis are rare and limited to a few cases in the literature. Although the mechanism of reactivation has not yet been clarified, in our patient, the surgery might have acted as a precipitating factor. CASE DESCRIPTION: The case involved a female 10-year-old patient with a history of type 1 HSV encephalitis since 24 months of age. Secondarily, the patient developed postherpetic epilepsy in the following years. At 10 years old, she was referred to the epilepsy surgery service, and an elective right temporal lobectomy was performed. After surgery, the patient experienced severe clinical deterioration characterized by fever, severe headache, and altered state of consciousness. Encephalitis was diagnosed based on a positive polymerase chain reaction for HSV in the cerebrospinal fluid. The symptoms remitted after 8 weeks of treatment with acyclovir. The histopathologic diagnosis was a chronic encephalitic process with late secondary parenchymal changes without specific viral cytopathic findings. The only limitation that persisted was related to fine movements of the left hand. One year after surgery, the patient rejoined her school activities and is currently free of seizures. CONCLUSIONS: HSV encephalitis is a rare but serious complication that should be suspected in cases of unexplained postoperative fever with altered consciousness, especially in patients with histories of encephalitic states. PMID- 26868429 TI - Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Multiple Sclerosis. AB - Several neurochemical, neuropathological, and experimental data suggest a possible role of oxidative stress in the ethiopathogenesis of multiple sclerosis(MS). Heme-oxygenases(HMOX) are an important defensive mechanism against oxidative stress, and HMOX1 is overexpressed in the brain and spinal cord of MS patients and in experimental autoimmune encephalomyelitis(EAE). We analyzed whether common polymorphisms affecting the HMOX1 and HMOX2 genes are related with the risk to develop MS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations(CNVs) of these genes in 292 subjects MS and 533 healthy controls, using TaqMan assays. The frequencies of HMOX2 rs1051308AA genotype and HMOX2 rs1051308A and HMOX1 rs2071746A alleles were higher in MS patients than in controls, although only that of the SNP HMOX2 rs1051308 in men remained as significant after correction for multiple comparisons. None of the studied polymorphisms was related to the age at disease onset or with the MS phenotype. The present study suggests a weak association between HMOX2 rs1051308 polymorphism and the risk to develop MS in Spanish Caucasian men and a trend towards association between the HMOX1 rs2071746A and MS risk. PMID- 26868430 TI - Alveolar recruitment of ficolin-3 in response to acute pulmonary inflammation in humans. AB - BACKGROUND: Ficolins serve as soluble recognition molecules in the lectin pathway of complement. They are known to participate in the systemic host-response to infection but their role in local pulmonary defence is still incompletely understood. The purpose of this study was to clarify whether acute lung and systemic inflammation induce recruitment of lectins in humans. METHODS: Fifteen healthy volunteers received LPS intravenously (IV) or in a lung subsegment on two different occasions. Volunteers were evaluated by consecutive blood samples and by bronchoalveolar lavage 2, 4, 6, 8, or 24h after LPS (n=3 in all groups), and gene expression patterns and protein levels of mannose-binding lectin (MBL) and ficolins were determined. RESULTS: Endobronchial LPS was associated with an increase in alveolar ficolin-3 and MBL levels (p<0.04 and p<0.001, respectively). IV LPS elicited a pronounced acute phase response with an increase in CRP (p<0.001) and plasma ficolin-1 protein levels (p<0.001), whereas no changes were observed in ficolin-1 gene expression patterns (p=0.11) or plasma protein levels of MBL, ficolin-2, or ficolin-3. CONCLUSIONS: LPS induces a tissue-specific recruitment of ficolin-3 and ficolin-1 in the lung and systemic compartment, respectively, suggesting an important role of distinct lectin complement pathway initiators in the local pulmonary and systemic host defence. PMID- 26868431 TI - Inhibitory function of NKT cells during early induction phase of nickel allergy. AB - Until now, metal allergies have been regarded as a Th1-type immune response. However, because the contribution of a Th2-type immune response has been suggested by clinical findings, we previously examined the Th2-type immune response during the development of metal allergies using a GATA-3 transgenic (GATA-3 Tg) mouse model. As a result, a Th2-type immunization reaction was suggested to be involved in the early phase of metal allergies. Recently, the involvement of NKT cells in metal allergies has been suggested. We examined this possibility using the activation of NKT cells and an NKT cell-deficient mouse model to determine the contribution of NKT cells to nickel allergy in the present study. In NKT cell-deficient mice, ear swelling was remarkably increased, compared with that in control mice. Also, in mice that had been treated with alpha-galactosylceramide (alpha-GalCer) to activate NKT cells, the ear swelling response was remarkably inhibited, compared with that in untreated mice. These facts show that NKT cells are involved in the inhibition of nickel allergy induced ear swelling responses. PMID- 26868432 TI - Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration. AB - BACKGROUND AND AIMS: Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. METHODS AND RESULTS: Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-alpha induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-gamma activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. CONCLUSIONS: Thus, our results support that GL root extract/powder and isovitexin exhibit anti atherosclerotic activities. PMID- 26868433 TI - Is common genetic variation at IRS1, ENPP1 and TRIB3 loci associated with cardiometabolic phenotypes in type 2 diabetes? An exploratory analysis of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 5. AB - BACKGROUND AND AIMS: Insulin resistance is a hallmark of type 2 diabetes (T2DM), it is often accompanied by defective beta-cell function (BF) and is involved in the pathophysiology of cardiovascular disease (CVD). Commonalities among these traits may recognize a genetic background, possibly involving the genetic variation of insulin signaling pathway genes. We conducted an exploratory analysis by testing whether common genetic variability at IRS1, ENPP1 and TRIB3 loci is associated with cardiovascular risk traits and metabolic phenotypes in T2DM. METHODS AND RESULTS: In 597 drug-naive, GADA-negative, newly-diagnosed T2DM patients we performed: 1) genotyping of 10 independent single-nucleotide polymorphisms covering ~ 90% of common variability at IRS1, ENPP1 and TRIB3 loci; 2) carotid artery ultrasound; 3) standard ECG (n = 450); 4) euglycaemic insulin clamp to assess insulin sensitivity; 5) 75 g-OGTT to estimate BF (derivative and proportional control) by mathematical modeling. False discovery rate of multiple comparisons was set at 0.20. After adjustment for age, sex and smoking status, rs4675095-T (IRS1) and rs4897549-A (ENPP1) were significantly associated with carotid atherosclerosis severity, whilst rs7265169-A (TRIB3) was associated with ECG abnormalities. Rs858340-G (ENPP1) was significantly associated with decreased insulin sensitivity, independently of age, sex and body-mass-index. No consistent relationships were found with BF. CONCLUSION: Some associations were found between intermediate phenotypes of CVD and common genetic variation of gatekeepers along the insulin signaling pathway. These results need be replicated to support the concept that in T2DM the CVD genetic risk clock may start ticking long before hyperglycemia appears. ClinicalTrials.gov Identifier: NCT01526720. PMID- 26868435 TI - A hidden aggregation-prone structure in the heart of hypoxia inducible factor prolyl hydroxylase. AB - Prolyl hydroxylase domain-containing protein 2 (PHD2), as one of the most important regulators of angiogenesis and metastasis of cancer cells, is a promising target for cancer therapy drug design. Progressive studies imply that abnormality in PHD2 function may be due to misfolding. Therefore, study of the PHD2 unfolding pathway paves the way for a better understanding of the influence of PHD2 mutations and cancer cell metabolites on the protein folding pathway. We study the unfolding of the PHD2 catalytic domain using differential scanning calorimetry (DSC), fluorescence spectroscopy, and discrete molecular dynamics simulations (DMD). Using computational and experimental techniques, we find that PHD2 undergoes four transitions along the thermal unfolding pathway. To illustrate PHD2 unfolding events in atomic detail, we utilize DMD simulations. Analysis of computational results indicates an intermediate species in the PHD2 unfolding pathway that may enhance aggregation propensity, explaining mutation independent PHD2 malfunction. PMID- 26868434 TI - cJun N-terminal kinase (JNK) phosphorylation of serine 36 is critical for p66Shc activation. AB - p66Shc-dependent ROS production contributes to many pathologies including ischemia/reperfusion injury (IRI) during solid organ transplantation. Inhibiting p66Shc activation may provide a novel therapeutic approach to prevent damage, which is poorly managed by antioxidants in vivo. Previous work suggested that pro oxidant and a pro-apoptotic function of p66Shc required mitochondrial import, which depended on serine 36 phosphorylation. PKCbeta has been proposed as S36 kinase but cJun N-terminal kinases (JNKs) may also phosphorylate this residue. To simulate the early stages of ischemia/reperfusion (IR) we either used H2O2 treatment or hypoxia/reoxygenation (HR). As during reperfusion in vivo, we observed increased JNK and p38 activity in mouse embryonic fibroblasts (MEFs) and HL-1 cardiomyocytes along with significantly increased p66ShcS36 phosphorylation, ROS production and cell damage. Application of specific inhibitors caused a pronounced decrease in p66ShcS36 phosphorylation only in the case of JNK1/2. Moreover, S36 phosphorylation of recombinant p66Shc by JNK1 but not PKCbeta was demonstrated. We further confirmed JNK1/2-dependent regulation of p66ShcS36 phosphorylation, ROS production and cell death using JNK1/2 deficient MEFs. Finally, the low ROS phenotype of JNK1/2 knockout MEFs was reversed by the phosphomimetic p66ShcS36E mutant. Inhibiting JNK1/2-regulated p66Shc activation may thus provide a therapeutic approach for the prevention of oxidative damage. PMID- 26868436 TI - Editorial: Noise on hospital wards--what have we learned? PMID- 26868438 TI - Endocrine disruptors: Reproductive consequences of analgesic use during pregnancy. PMID- 26868439 TI - Development of a more streamlined approach to pregnancy screening before nuclear medicine procedures. PMID- 26868441 TI - Erratum: 2,3-Diphenyl-2,3,5,6-tetra-hydro-4H-1,3-thia-zin-4-one. Corrigendum. AB - In the paper by Yennawar & Silverberg [Acta Cryst. (2014), E70, o133], the conformation of the thiazine ring was reported incorrectly.[This corrects the article DOI: 10.1107/S1600536814000324.]. PMID- 26868437 TI - A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. AB - The rearranged during transfection (RET) proto-oncogene was identified in 1985 and, very soon thereafter, a rearrangement named RET/PTC was discovered in papillary thyroid carcinoma (PTC). After this discovery, other RET rearrangements were found in PTCs, particularly in those induced by radiation. For many years, it was thought that these genetic alterations only occurred in PTC, but, in the past couple of years, some RET/PTC rearrangements have been found in other human tumours. 5 years after the discovery of RET/PTC rearrangements in PTC, activating point mutations in the RET proto-oncogene were discovered in both hereditary and sporadic forms of medullary thyroid carcinoma (MTC). In contrast to the alterations found in PTC, the activation of RET in MTC is mainly due to activating point mutations. Interestingly, in the past year, RET rearrangements that were different to those described in PTC were observed in sporadic MTC. The identification of RET mutations is relevant to the early diagnosis of hereditary MTC and the prognosis of sporadic MTC. The diagnostic and prognostic role of the RET/PTC rearrangements in PTC is less relevant but still important in patient management, particularly for deciding if a targeted therapy should be initiated. In this Review, we discuss the pathogenic, diagnostic and prognostic roles of the RET proto-oncogene in both PTC and MTC. PMID- 26868440 TI - Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans. AB - OBJECTIVE: Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels. RESEARCH DESIGN AND METHODS: Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic beta-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits. RESULTS: Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P <= 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P <= 0.043). The effects of short term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes. CONCLUSIONS: Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae. PMID- 26868442 TI - Integrating forest ecosystem services into the farming landscape: A stochastic economic assessment. AB - The objective of this study was to assess how payments for ecosystem services could assist plantation forestry's integration into pastoral dairy farming in order to improve environmental outcomes and increase business resilience to both price uncertainty and production limits imposed by environmental policies. Stochastic Dominance (SD) criteria and portfolio analysis, accounting for farmers' risk aversion levels, were used to rank different land-use alternatives and landscapes with different levels of plantation forestry integration. The study was focused on a modal 200-ha dairy farm in the Lake Rotorua Catchment of the Central North Island region of New Zealand, where national environmental policies are being implemented to improve water quality and reduce greenhouse gas emissions. Nitrogen and carbon payments would help farmers improve early cash flows for forestry, provide financial leverage to undertake afforestation projects and contribute to improved environmental outcomes for the catchment. The SD criteria demonstrated that although dairy farming generates the highest returns, plantation forestry with nitrogen and carbon payments would be a preferred alternative for landowners with relatively low risk aversion levels who consider return volatility and environmental limits within their land-use change criteria. Using the confidence premium concept, environmental payments to encourage plantation forestry into the landscape were shown to be lower when the majority of landowners are risk averse. The certainty equivalence approach helped to identify the optimal dairy-forestry portfolio arrangements for landowners of different levels of risk aversion, intensities of dairy farming (status quo and intensified) and nitrogen prices. At low nitrogen prices, risk neutral farmers would choose to afforest less than half of the farm and operate at the maximum nitrogen allowance, because dairy farming at both intensities provides the highest return among the different land uses available. However, at relatively low risk aversion levels, farmers would operate at levels below the maximum nitrogen allowance by including plantation forestry to a greater extent, compared to risk neutral farmers, due to its more certain returns. At a high nitrogen price of $400/kg, plantation forestry would completely subsume dairying, across risk aversion and intensity levels. These results confirm that plantation forestry as well as being an environmentally sound land-use alternative, also reduces uncertainty for landowners that are exposed to volatile international markets for dairy commodities. PMID- 26868445 TI - Characterization of synthetic dyes by comprehensive two-dimensional liquid chromatography combining ion-exchange chromatography and fast ion-pair reversed phase chromatography. AB - In the late 19th century, newly invented synthetic dyes rapidly replaced the natural dyes on the market. The characterization of mixtures of these so-called early synthetic dyes is complicated through the occurrence of many impurities and degradation products. Conventional one-dimensional liquid chromatography does not suffice to obtain fingerprints with sufficient resolution and baseline integrity. Comprehensive two-dimensional liquid chromatography (LC*LC) is employed in this study, with ion-exchange chromatography in the first dimension and fast ion-pair liquid chromatography in the second. Retention in the first dimension is largely determined by the number of charges, while the selection of a small ion-pair reagent (tetramethylammonium hydroxide) in the second dimension causes retention to be largely determined by the molecular structure of the dye. As a result, there is a high degree of orthogonality of the two dimensions, similar to the values typically encountered in GC*GC. The proposed LC*LC method shows a theroretical peak capacity of about 2000 in an analysis time of about three hours. Clear, informative fingerprints are obtained that open a way to a more efficient characterization of dyes used in objects of cultural heritage. PMID- 26868443 TI - Moving Toward Integrative, Multidimensional Research in Modern Psychiatry: Lessons Learned From Fragile X Syndrome. AB - The field of psychiatry is approaching a major inflection point. The basic science behind cognition, emotion, behavior, and social processes has been advancing rapidly in the past 20 years. However, clinical research supporting the classification system in psychiatry has not kept up with these scientific advances. To begin organizing the basic science of psychiatry in a comprehensive manner, we begin by selecting fragile X syndrome, a neurogenetic disease with cognitive-behavioral manifestations, to illustrate key concepts in an integrative, multidimensional model. Specifically, we describe key genetic and molecular mechanisms (e.g., gamma-aminobutyric acidergic dysfunction and metabotropic glutamate receptor 5-associated long-term depression) relevant to the pathophysiology of fragile X syndrome as well as neural correlates of cognitive-behavioral symptoms. We then describe what we have learned from fragile X syndrome that may be applicable to other psychiatric disorders. We conclude this review by discussing current and future opportunities in diagnosing and treating psychiatric diseases. PMID- 26868444 TI - Ablation of Type III Adenylyl Cyclase in Mice Causes Reduced Neuronal Activity, Altered Sleep Pattern, and Depression-like Phenotypes. AB - BACKGROUND: Although major depressive disorder (MDD) has low heritability, a genome-wide association study in humans has recently implicated type 3 adenylyl cyclase (AC3; ADCY3) in MDD. Moreover, the expression level of AC3 in blood has been considered as a MDD biomarker in humans. Nevertheless, there is a lack of supporting evidence from animal studies. METHODS: We employed multiple approaches to experimentally evaluate if AC3 is a contributing factor for major depression using mouse models lacking the Adcy3 gene. RESULTS: We found that conventional AC3 knockout (KO) mice exhibited phenotypes associated with MDD in behavioral assays. Electroencephalography/electromyography recordings indicated that AC3 KO mice have altered sleep patterns characterized by increased percentage of rapid eye movement sleep. AC3 KO mice also exhibit neuronal atrophy. Furthermore, synaptic activity at cornu ammonis 3-cornu ammonis 1 synapses was significantly lower in AC3 KO mice, and they also exhibited attenuated long-term potentiation as well as deficits in spatial navigation. To confirm that these defects are not secondary responses to anosmia or developmental defects, we generated a conditional AC3 floxed mouse strain. This enabled us to inactivate AC3 function selectively in the forebrain and to inducibly ablate it in adult mice. Both AC3 forebrain-specific and AC3 inducible knockout mice exhibited prodepression phenotypes without anosmia. CONCLUSIONS: This study demonstrates that loss of AC3 in mice leads to decreased neuronal activity, altered sleep pattern, and depression-like behaviors, providing strong evidence supporting AC3 as a contributing factor for MDD. PMID- 26868446 TI - In situ solvothermal synthesis of metal-organic framework coated fiber for highly sensitive solid-phase microextraction of polycyclic aromatic hydrocarbons. AB - The present work reported a facile and simple in situ solvothermal growth method for immobilization of metal-organic framework UiO-66 via covalent bonding on amino functional silica fiber for highly sensitive solid-phase microextraction (SPME) of ten polycyclic aromatic hydrocarbons (PAHs) by coupling with gas chromatography-mass spectrometry (GC-MS) analysis. The developed SPME coated fiber has been characterized through SEM, TGA and XRD, confirmed the coating thickness of ~25MUm with high thermal and chemical stability. Under optimized conditions, the obtained method exhibited satisfactory linearity in range of 1.0 5000.0ngL(-1) for all the PAHs. The low detection limits were from 0.28ngL(-1) to 0.60ngL(-1) (S/N=3). The UiO-66 coated fibers showed good repeatability (RSDs less than 8.2%, n=5) and satisfying reproducibility between fiber to fiber (RSDs less than 8.9%, n=5). This method was successfully used for simultaneous determination of ten PAHs from Minjiang water and soil samples with satisfactory recoveries of 87.0-113.6% and 83.8-116.7%, respectively. Experimental results shows that the chemical bonding approach has dramatically improve the stability and lifetime of pure MOFs coating for SPME in sample pretreatment. PMID- 26868447 TI - Development of a capillary electrophoresis method for the analysis in alkaline media as polyoxoanions of two strategic metals: Niobium and tantalum. AB - Tantalum (Ta) and niobium (Nb) are two strategic metals essential to several key sectors, like the aerospace, gas and oil, nuclear and electronic industries, but their separation is really difficult due to their almost identical chemical properties. Whereas they are currently produced by hydrometallurgical processes using fluoride-based solutions, efforts are being made to develop cleaner processes by replacing the fluoride media by alkaline ones. However, methods to analyze Nb and Ta simultaneously in alkaline samples are lacking. In this work, we developed a capillary zone electrophoresis (CE) method able to separate and quantify Nb and Ta directly in alkaline media. This method takes advantage of the hexaniobate and hexatantalate ions which are naturally formed at pH>9 and absorb in the UV domain. First, the detection conditions, the background electrolyte (BGE) pH, the nature of the BGE co-ion and the internal standard (IS) were optimized by a systematic approach. As the BGE counter-ion nature modified the speciation of both ions, sodium- and lithium-based BGE were tested. For each alkaline cation, the BGE ionic strength and separation temperature were optimized using experimental designs. Since changes in the migration order of IS, Nb and Ta were observed within the experimental domain, the resolution was not a monotonic function of ionic strength and separation temperature. This forced us to develop an original data treatment for the prediction of the optimum separation conditions. Depending on the consideration of either peak widths or peak symmetries, with or without additional robustness constraints, four optima were predicted for each tested alkaline cation. The eight predicted optima were tested experimentally and the best experimental optimum was selected considering analysis time, resolution and robustness. The best separation was obtained at 31.0 degrees C and in a BGE containing 10mM LiOH and 35mM LiCH3COO.The separation voltage was finally optimized, resulting in the separation of Nb, Ta, and IS in less than 2.5min, which is three times faster than any CE method ever reported for the separation of Nb and Ta (acidic media included). Some figures of merit of the method were determined such as linearity ranges and limits of quantitation. Finally, the method was successfully applied to the analysis of a real industrial sample. PMID- 26868449 TI - Delayed wound healing and dysregulation of IL6/STAT3 signalling in MSCs derived from pre-diabetic obese mice. AB - Metabolic dysfunction that occurs in obesity and Type 2 diabetes results in a low level inflammatory state which impacts on mesenchymal stem cells (MSCs) capacity to promote wound healing. The ability of either recombinant Interleukin-6 (rIL6) or pioglitazone to modulate MSC migration, essential for wound healing, by targeting the inflammation-modulated IL6/STAT3 signalling pathway was therefore investigated in bone marrow-derived MSCs from control (C57BL/6J) and pre-diabetic obese mice (B6. Cg-Lepob/J). The population doubling time, in vitro wound closure and mRNA expression profile of 84 genes involved in the IL6/STAT3 signalling pathway were assessed. IL6/STAT3 signalling dysregulation, caused by IL6 deficiency, resulted in skewing of the immune modulatory properties of MSCs to favour a pro-inflammatory profile. This could be nullified by addition of either rIL6 or conventional diabetes treatment. Therapies to improve diabetic wound healing should therefore focus on the cellular changes induced by the pathological inflammatory micro-environment. PMID- 26868450 TI - No Neonate Left Behind: A QI Approach to Critical Congenital Heart Screening in the NICU. PMID- 26868448 TI - Pigment epithelium-derived factor (PEDF) regulates metabolism and insulin secretion from a clonal rat pancreatic beta cell line BRIN-BD11 and mouse islets. AB - Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat beta-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced beta-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation. PMID- 26868452 TI - MY APPROACH to testosterone replacement in older men. PMID- 26868451 TI - Sub-nanometre resolution of atomic motion during electronic excitation in phase change materials. AB - Phase-change materials based on Ge-Sb-Te alloys are widely used in industrial applications such as nonvolatile memories, but reaction pathways for crystalline to-amorphous phase-change on picosecond timescales remain unknown. Femtosecond laser excitation and an ultrashort x-ray probe is used to show the temporal separation of electronic and thermal effects in a long-lived (>100 ps) transient metastable state of Ge2Sb2Te5 with muted interatomic interaction induced by a weakening of resonant bonding. Due to a specific electronic state, the lattice undergoes a reversible nondestructive modification over a nanoscale region, remaining cold for 4 ps. An independent time-resolved x-ray absorption fine structure experiment confirms the existence of an intermediate state with disordered bonds. This newly unveiled effect allows the utilization of non thermal ultra-fast pathways enabling artificial manipulation of the switching process, ultimately leading to a redefined speed limit, and improved energy efficiency and reliability of phase-change memory technologies. PMID- 26868453 TI - MY APPROACH to a patient with atrial fibrillation and dementia. PMID- 26868454 TI - Molecular cloning and characterization of a steroidogenic enzyme, 17beta hydroxysteroid dehydrogenase type 14, from the stony coral Euphyllia ancora (Cnidaria, Anthozoa). AB - Sex steroids play a fundamental role not only in reproduction but also in various other biological processes in vertebrates. Although the presence of sex steroids has been confirmed in cnidarians (e.g., coral, sea anemone, jellyfish, and hydra), which are basal metazoans, only a few studies to date have characterized steroidogenesis-related genes in cnidarians. Based on a transcriptomic analysis of the stony coral Euphyllia ancora, we identified the steroidogenic enzyme 17beta-hydroxysteroid dehydrogenase type 14 (17beta-hsd 14), an oxidative enzyme that catalyzes the NAD(+)-dependent inactivation of estrogen/androgen (estradiol to estrone and testosterone to androstenedione) in mammals. Phylogenetic analysis showed that E. ancora 17beta-Hsd 14 (Ea17beta-Hsd 14) clusters with other animal 17beta-HSD 14s but not with other members of the 17beta-HSD family. Subsequent quantitative RT-PCR analysis revealed a lack of correlation of Ea17beta-hsd 14 transcript levels with the coral's reproductive cycle. In addition, Ea17beta-hsd 14 transcript and protein were detected in all tissues examined, such as the tentacles, mesenterial filaments, and gonads, at similar levels in both sexes, as determined by quantitative RT-PCR analysis and Western blotting with an anti Ea17beta-Hsd 14 antibody. Immunohistochemical analysis revealed that Ea17beta-Hsd 14 is mainly distributed in the endodermal regions of the polyps, but the protein was also observed in all tissues examined. These results suggest that Ea17beta Hsd 14 is involved in important functions that commonly occur in endodermal cells or has multiple functions in different tissues. Our data provide information for comparison with advanced animals as well as insight into the evolution of steroidogenesis-related genes in metazoans. PMID- 26868455 TI - Revised Risk Estimates for MRSA Infection in Patients with Intermittent Versus Persistent MRSA Nares Colonization. PMID- 26868456 TI - Toxicity mechanisms of arsenic that are shared with neurodegenerative diseases and cognitive impairment: Role of oxidative stress and inflammatory responses. AB - Arsenic (As) is a worldwide naturally occurring metalloid. Human chronic exposure to inorganic As compounds (iAs), which are at the top of hazardous substances (ATSDR, 2013), is associated with different diseases including cancer and non- cancerous diseases. The neurotoxic effects of iAs and its methylated metabolites have been demonstrated in exposed populations and experimental models. Impaired cognitive abilities have been described in children and adults chronically exposed to iAs through drinking water. Even though different association studies failed to demonstrate that As causes neurodegenerative diseases, several toxicity mechanisms of iAs parallel those mechanisms associated with neurodegeneration, including oxidative stress and inflammation, impaired protein degradation, autophagy, and intracellular accumulation, endoplasmic reticulum stress, and mitochondrial dysfunction. Additionally, different reports have shown that specifically in brain tissue, iAs and its metabolites induce hyper phosphorylation of the tau protein and over-regulation of the amyloid precursor protein, impaired neurotransmitters synthesis and synaptic transmission, increased glutamate receptors activation, and decreased glutamate transporters expression. Interestingly, increased and sustained pro-inflammatory responses mediated by cytokines and related factors, seems to be the triggering factor for all of such cellular pathological effects. Therefore, this review proposes that iAs-associated cognitive impairment could be the result of the activation of pro inflammatory responses in the brain tissue, which also may favor neurodegeneration or increase the risk for neurodegenerative diseases in exposed human populations. PMID- 26868458 TI - Rejoinder: In Defence of Medical Anthropology. AB - The claim that medical anthropology is failing medicine is wrong. Certain areas of medical anthropology contribute to theory, while others are intended to be of more clinical use. The problems that this latter category can encounter are rooted not within anthropology, but within medicine. For those practitioners that do choose to engage with anthropological ideas, it impacts in such a way that it cannot be readily proved within empirical data. This does not, however, mean it does not make significant and lasting contributions in the clinical setting. PMID- 26868457 TI - Unprecedented Oxycyanation of Methylenecyclopropanes for the Facile Synthesis of Benzoxazine Compounds Containing a Cyano Group. AB - A novel intramolecular oxycyanation of methylenecyclopropanes is reported that proceeds through oxidative cleavage of the N-CN bond and subsequent palladium transfer from N to O of the amide group. A range of substituted benzo[d][1,3]oxazines with a cyano group are readily furnished by this newly developed oxycyanation reaction. Tris(4-trifluoromethylphenyl)phosphine as a ligand has been found to be crucial to effectively promote the transformation with high chemo- and regioselectivity. Moreover, the reaction outcome can be significantly affected by the electronic effect of the acyl group attached to the nitrogen atom of methylenecyclopropanes. When R(3) is a chloromethyl group, the pyrrolo[2,3-b]quinoline derivative is obtained by thermal-induced [3+2] cycloaddition of methylenecyclopropane to the methanediimine intermediate. PMID- 26868459 TI - Figuring Out Type 2 Diabetes through Genetic Research: Reckoning Kinship and the Origins of Sickness. AB - Genetic research on type 2 diabetes serves as a point of departure in this paper. Drawing together classic work in the anthropology of medical epistemologies and the recent revitalization of kinship studies, the paper has two main objectives: (1) further unsettling a portrait of biomedicine as having a single overarching epistemological orientation that locates the origins of disease squarely within individual human bodies; and (2) inviting further reflection and discussion about history, social structures and cultural norms as bona fide causes of disease. The paper shows that causal roles ascribed to history, social structures and cultural norms through genetic research on diabetes hinge on underscoring evolutionary 'blood relations' between people, as well as between human and 'lower' nonhuman beings. It is argued that type 2 diabetes has not thoroughly undergone geneticization, but, partly through genetic research, it has undergone greater medicalization. Despite broad consensus that 'the environment' is the root cause of increased type 2 diabetes incidence, proposed remedies still tend to privilege clinical management. PMID- 26868460 TI - Rejoinder: Genetic Research into the Causes of Type 2 Diabetes Mellitus. AB - Type 2 diabetes mellitus is a disease of substantial health and economic impact in Western societies. Its prevalence has drastically increased in the latter half of the 20th century, largely due to the ready availability of large quantities of calorie-rich foods and the technology-driven reduction in routine, daily exercise. Yet basic scientists repeatedly emphasize the prominent genetic basis for Type 2 diabetes mellitus, even though its widespread occurrence has appeared at a rate too fast to be accounted for by genetic change. This phenomenon emphasizes how the human gene pool has evolved as an adaptation to an ancient societal condition and when the environment changes rapidly both it and our genetic structure can contribute to the development of disease. PMID- 26868461 TI - 'Sacraments' in the Hospital: Exploring the Magic and Religion of Recovery. AB - This article proposes to look at the ritual dimension of hospital work, a chain of words and acts, which fill patients with hope for a 'future life'. Conventional boundaries between magic, science and religion are reconsidered. The author argues that biomedicine, far from being a cultural no-man's land, represents the basic values of culture. It provides a space where doctors, nurses and patients find their deepest convictions and values demonstrated and confirmed. Medical words and interventions express and re-create people's belief in the canons of science and biomedicine as ultimate truth. Pointing out the religious dimension of medicine in no way belittles medicine's role and therapeutic efficacy. Rather it provides us with a better understanding of the 'mechanics' of recovery. PMID- 26868462 TI - 'La Muse Malade', 'The Fool's Perceptions' & 'Il Furore dell'Arte': An Examination of the Socio-cultural Construction of Genius through Madness. AB - The cultural interplay of madness and genius is entrenched in, although not exclusive to, Western intellectual tradition. In order to trace both their reflection of and influence on each other, this paper seeks to rupture the alliance of these terms with their clinical 'pseudonyms' of mental illness and creativity. Drawing on preceding psychiatric research, as well as both literary criticism and anthropological theory, this paper traces the patchwork of metaphors and cultural imaginings that make up the genius/madness myth-the socio cultural construction of genius through madness. With particular focus on the cyclical processes of cultural mythmaking it tracks the elements of this construction, initially diachronically, and then through psychiatry and its effect on social thought. Finally, an assessment of the social implications of this myth illustrates that not only is genius socio-culturally constructed through madness but that madness itself is also fabricated through genius in the binding circularity of societal mythmaking. The paper argues that this socio cultural construction legitimates and elevates, shackles and constrains, having societal implications far beyond the reaches of its own confines. PMID- 26868463 TI - Competing Health Models in Mexico: An Ideological Dialogue between Indian and Hegemonic Views. AB - Models of health in Mexico emerge out of a conflictive interaction between two systems of knowledge and values: one from Western culture, considered superior and legitimate (by the majority), and an Indian one, regarded as inferior. The conflicts that arise from this ideological difference affect the success of public health programs directed to broad sectors of population with an indigenous culture. This gives rise to many problems in the treatment of Indian peoples, limiting their chances of a more adequate health system. This article focuses on how ideologies are negotiated between agents from the national hegemonic health system and the traditional healers, using as an example an interethnic health program developed in a mostly Indian municipality, Cuetzalan, in the Mexican state of Puebla. In this program intercultural interaction established a dialogue between the two health models, explicitly aiming to generate more adequate health programs for Indian communities. The attempt however was permeated by ideological resistance within an interethnic relationship framed by national and local interpretations of the value of indigenous knowledge. PMID- 26868464 TI - Repetition and Repertoires: The Creation of Cultural Differences in Dutch Mental Health Care. AB - This paper explores how culture and cultural differences are created and used to maintain power of definition in mental health care. The author argues that although in mental health care an open approach in care for immigrants is stimulated, cultural differences are strategically used to maintain the status quo of mental health care and mental health professionals. The result is that such strategies keep immigrants in a marginal position. In mental health care, immigrants belong to a classificatory anomaly or, in processual terms, to liminal personae. The author concludes that interaction in mental health care is a manifestation and reproduction of larger class, racial, ethnic and gender conflicts in the broader society. PMID- 26868465 TI - Patient support and advocacy organizations: partners in promoting awareness and improving the lives of patients with oral and maxillofacial disease. PMID- 26868466 TI - WhatsApp: a telemedicine platform for facilitating remote oral medicine consultation and improving clinical examinations. AB - OBJECTIVE: Increased use of smartphone and related software applications has created a new era in clinical data exchange among patients and clinicians. This study describes use of the smartphone-based application WhatsApp to share clinical oral medicine information. STUDY DESIGN: Clinical images and related questions were submitted by general dentists, physicians, dental hygienists, and patients to the authors via WhatsApp. For each submission, a clinical impression was made and categorized as traumatic, infective, neoplastic, autoimmune, or unclassified. Submissions were summarized by sender type, number of photographs per sender, and category of question. Patients were invited to undergo a clinical examination with biopsy, when indicated. The telemedicine impression was compared to the clinicopathologic diagnosis. RESULTS: Three hundred and thirty-nine images were received for 96 patients; 92 (95.8%) patients underwent clinicopathologic examination, and 45 (49%) received a biopsy. General dentists (62%) and dental hygienists (26%) were the most frequent senders. The most common question was related to diagnosis (56%). The telemedicine impression agreed with the clinicopathologic assessment for 82% of cases. CONCLUSIONS: Telemedicine applications, such as WhatsApp, can support communication about oral conditions among clinicians and patients. Telemedicine consultation reduced geographic barriers to initial clinical consultation and encouraged the significant majority of patients to pursue expert clinical examination. PMID- 26868467 TI - Characterization of pain originating from oral mucosal lesions. AB - OBJECTIVE: The aim of the study was to characterize pain associated with oral mucosal lesions. STUDY DESIGN: A cross-sectional study was performed in patients diagnosed with localized mucosal pain originating from acute ulcers (AUs), herpes infections (HIs), and immune-mediated chronic diseases (IMCDs). Pain-related features, including intensity (VAS-I), perceived unpleasantness (VAS-U), functional impairment (VAS-F), and effect on quality of life (VAS-Q), were recorded using a 10-cm visual analogue scale (VAS). Waking from sleep, provoking, and alleviating factors were assessed by questionnaires. RESULTS: Sixty-three patients aged 19 to 82 years (47.22 +/- 17.20 years) were examined over the study period. These included 18 patients with AUs, 21 with HIs, and 24 with IMCDs. At rest, VAS-U was significantly higher than VAS-I for all groups, and VAS-F was higher for lesions located on the tongue or lips. Up to 80% of patients described the pain as "burning." Differences between groups were not observed for all other parameters measured. Pain woke the patients from sleep in almost half of cases. VAS-I and VAS-U were not related to size or number of lesions. CONCLUSIONS: Mucosal pain is generally burning in quality, with a higher level of pain-related unpleasantness than pain intensity. In about half of the cases, pain awakens the person from sleep, a feature that correlated to female gender and pain intensity. Pain intensity or unpleasantness was not related to the size or number of lesions. PMID- 26868468 TI - Compromised salivary parameters of children with juvenile idiopathic arthritis. AB - OBJECTIVE: To evaluate the salivary parameters of individuals with juvenile idiopathic arthritis (JIA) and determine if there is a correlation with the simplified oral hygiene index (OHI-S). STUDY DESIGN: Stimulated whole saliva was collected from children, aged 6 to 12 years, with JIA (n = 36) and compared with saliva from a control group (CG) composed of healthy children matched by demographic characteristics (n = 36). Salivary parameters evaluated were amylase and peroxidase activities, calcium, phosphate, and total sialic acid concentration. Data were compared by two-tailed Student's t test, and salivary parameters were evaluated for correlations with OHI-S by Spearman's correlation. RESULTS: The JIA group had a statistically significant reduction in all salivary parameters: alpha-amylase (20%) (CG, 9.84 +/- 4.23; JIA 4.80 +/- 3.10) and peroxidase (55%) (CG, 35.05 +/- 14.97; JIA, 15.78 +/- 6.44) activities, total sialic acid (25%) (CG, 0.024 +/- 0.01; JIA, 0.010 +/- 0.04), calcium (13%) (CG, 6.26 +/- 2.26; JIA, 5.44 +/- 2.26) and phosphate (50%) (CG, 10.88 +/- 1.49; JIA, 5.45 +/- 0.88) concentration compared with the CG (P <= .05). There were no significant correlations between the salivary parameters and OHI-S in either group. CONCLUSION: JIA patients showed a reduction of different salivary parameters involved in maintaining oral health. PMID- 26868469 TI - Low-level laser therapy versus 5% amlexanox: a comparison of treatment effects in a cohort of patients with minor aphthous ulcers. AB - OBJECTIVE: The aim of the study was to compare the treatment effects of 5% amlexanox and low-level laser therapy (LLLT) in a cohort of patients who experienced minor aphthous stomatitis. STUDY DESIGN: A clinical trial was performed between 2012 and 2014 on 50 participants having minor aphthous ulcers. Group A participants were treated with amlexanox oral paste (lexanox 5% oral paste), and group B participants were treated with LLLT. Pain scores and sizes of ulcers were measured on the first, third, and seventh days of treatment in both groups. Data were analyzed using paired t test and independent t test. RESULTS: No significant difference was observed between the two groups with respect to pain level on the first and seventh days of treatment. CONCLUSIONS: Both amlexanox and LLLT were equally effective in relieving pain associated with minor aphthous stomatitis. Both groups showed significant reduction in ulcer sizes and in pain scores. PMID- 26868470 TI - Validation of cone beam computed tomography-based tooth printing using different three-dimensional printing technologies. AB - OBJECTIVE: Our aim was to determine the accuracy of 3-dimensional reconstructed models of teeth compared with the natural teeth by using 4 different 3 dimensional printers. STUDY DESIGN: This in vitro study was carried out using 2 intact, dry adult human mandibles, which were scanned with cone beam computed tomography. Premolars were selected for this study. Dimensional differences between natural teeth and the printed models were evaluated directly by using volumetric differences and indirectly through optical scanning. Analysis of variance, Pearson correlation, and Bland Altman plots were applied for statistical analysis. RESULTS: Volumetric measurements from natural teeth and fabricated models, either by the direct method (the Archimedes principle) or by the indirect method (optical scanning), showed no statistical differences. The mean volume difference ranged between 3.1 mm(3) (0.7%) and 4.4 mm(3) (1.9%) for the direct measurement, and between -1.3 mm(3) (-0.6%) and 11.9 mm(3) (+5.9%) for the optical scan. A surface part comparison analysis showed that 90% of the values revealed a distance deviation within the interval 0 to 0.25 mm. CONCLUSIONS: Current results showed a high accuracy of all printed models of teeth compared with natural teeth. This outcome opens perspectives for clinical use of cost-effective 3-dimensional printed teeth for surgical procedures, such as tooth autotransplantation. PMID- 26868471 TI - Accuracy of diagnosis of salivary gland tumors with the use of ultrasonography, computed tomography, and magnetic resonance imaging: a meta-analysis--a commentary. PMID- 26868472 TI - Reply to "Accuracy of diagnosis of salivary gland tumors with the use of ultrasonography, computed tomography, and magnetic resonance imaging: a meta analysis--a commentary". PMID- 26868473 TI - CBCT constancy controls: how user-friendly is the new phantom? PMID- 26868474 TI - Case report: An unusual presentation of oral acute graft-versus-host-disease in a haploidentical hematopoietic stem cell transplant recipient. AB - Oral acute graft-versus-host disease (aGVHD) is a significant sequelae of allogeneic hematopoietic stem cell transplantation (HSCT). Presently, transplant physicians have to diagnose GVHD based on clinical judgment by interpreting available clinical and relevant laboratory findings. As such, characterization of diagnostic and distinctive clinical signs and symptoms of GVHD is essential for diagnosis and grading. The oral features of aGVHD have been reported infrequently and remain ill defined, unlike in oral chronic GVHD. The report describes an atypical and painful presentation of oral aGVHD in a 15-year-old boy, 16 days after haploidentical HSCT, who presented with swollen lips, herpetiform ulcerations, and erythematous fungiform papilla. PMID- 26868476 TI - Canine and feline retinal lymphoma: a retrospective review of 12 cases. AB - This retrospective study identified 12 cases (6 canine and 6 feline) of ocular lymphoma with extensive retinal involvement and relative sparing of other ocular tissues. Our objectives were to describe the morphologic and immunohistochemical features of retinal lymphoma, assess the degree of correlation to the human counterpart, assign subtypes based on the veterinary-adapted WHO classification system, and promote accurate reporting of retinal involvement in cases of intraocular lymphoma. Our findings suggest that a distinct retinal tropism is quite rare, representing approximately 1% of all cases of canine and feline ocular lymphoma. No breed or sex predispositions were identified. The mean age of the affected animal was 7 years (range 4-10) and 11 years (range 6-19) for dogs and cats, respectively. Nine cases (5 canine and 4 feline) were classified as diffuse large B-cell lymphoma (DLBCL) subtype. The remaining cases were classified as peripheral T-cell lymphoma (PTCL). PMID- 26868475 TI - Chronic cocaine disrupts neurovascular networks and cerebral function: optical imaging studies in rodents. AB - Cocaine abuse can lead to cerebral strokes and hemorrhages secondary to cocaine's cerebrovascular effects, which are poorly understood. We assessed cocaine's effects on cerebrovascular anatomy and function in the somatosensory cortex of the rat's brain. Optical coherence tomography was used for in vivo imaging of three-dimensional cerebral blood flow (CBF) networks and to quantify CBF velocities (CBFv), and multiwavelength laser-speckle-imaging was used to simultaneously measure changes in CBFv, oxygenated (Delta[HbO2] ) and deoxygenated hemoglobin (Delta[HbR] ) concentrations prior to and after an acute cocaine challenge in chronically cocaine exposed rats. Immunofluorescence techniques on brain slices were used to quantify microvasculature density and levels of vascular endothelial growth factor (VEGF). After chronic cocaine (2 and 4 weeks), CBFv in small vessels decreased, whereas vasculature density and VEGF levels increased. Acute cocaine further reduced CBFv and decreased Delta[HbO2] and this decline was larger and longer lasting in 4 weeks than 2 weeks cocaine exposed rats, which indicates that risk for ischemia is heightened during intoxication and that it increases with chronic exposures. These results provide evidence of cocaine-induced angiogenesis in cortex. The CBF reduction after chronic cocaine exposure, despite the increases in vessel density, indicate that angiogenesis was insufficient to compensate for cocaine-induced disruption of cerebrovascular function. PMID- 26868477 TI - Chronic cocaine exposure in adolescence: Effects on spatial discrimination reversal, delay discounting, and performance on fixed-ratio schedules in mice. AB - Adolescence is marked by the continued development of the neural pathways that support choice and decision-making, particularly those involving dopamine signaling. Cocaine exposure during adolescence may interfere with this development and manifest as increased perseveration and delay discounting in adulthood, behavioral processes that are related to drug addiction. Adolescent mice were exposed to 30mg/kg/day of cocaine (n=11) or saline vehicle (n=10) for 14days and behavior was assessed in adulthood. In Experiment 1, performance on a spatial-discrimination-reversal procedure was evaluated. In the first two sessions following the first reversal, cocaine-exposed mice produced more preservative errors relative to controls. In Experiment 2, cocaine-exposed mice displayed steeper delay discounting than saline-exposed mice, effects that were reversed by acute cocaine administration. Experiment 3 examined responding maintained by a range of fixed-ratio schedules of reinforcement. An analysis based on a theoretical framework called Mathematical Principles of Reinforcement (MPR) was applied to response-rate functions of individual mice. According to MPR, differences in response-rate functions in adulthood were due to a steepening of the delay-of-reinforcement gradient, disrupted motoric capacity (lower maximum response rates), and enhanced reinforcer efficacy for the adolescent cocaine- compared with saline-exposed mice. Overall, these experiments suggest that chronic exposure to cocaine during adolescence may impair different features of 'executive functions' in adulthood, and these may be related to distortions in the impact of reinforcing events. PMID- 26868478 TI - Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity. AB - Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories. PMID- 26868480 TI - Aseptic technique for accessing central venous catheters: applying a standardised tool to audit 'scrub the hub' practices. AB - BACKGROUND: To reduce the risk of infections associated with indwelling central venous catheters (CVCs), practices for hub disinfection have been widely promoted. The objective of this study was to design and implement a standardised tool to monitor compliance with 'scrub the hub' practices at an Australian centre. METHODS: Review of existing literature and recommendations regarding scrub the hub practices was performed to identify nine key components that could be audited by direct observation of staff in clinical areas. The tool was reviewed by stakeholders in infection prevention, infectious diseases and senior nursing roles prior to pilot evaluation. RESULTS: Twenty attempts to access a CVC were audited. In all instances, scrub the hub practices were commenced. However, a 15-second scrub was performed in only 60% of cases, and the hub was permitted to dry in only 65% of instances. With respect to maintaining an aseptic field, the overall compliance was 40%, and compliance was lowest for maintenance of a non-touch technique for key parts and sites, and hand hygiene practices following CVC access. CONCLUSIONS: A standardised clinical audit tool for monitoring aseptic access of CVCs enabled identification of practices amendable to targeted intervention and education, such as duration of hub disinfection. This tool would be readily utilised to facilitate quality improvement initiatives in a range of healthcare contexts, including high-risk inpatient and ambulatory care settings. PMID- 26868479 TI - Tc1 mouse model of trisomy-21 dissociates properties of short- and long-term recognition memory. AB - The present study examined memory function in Tc1 mice, a transchromosomic model of Down syndrome (DS). Tc1 mice demonstrated an unusual delay-dependent deficit in recognition memory. More specifically, Tc1 mice showed intact immediate (30sec), impaired short-term (10-min) and intact long-term (24-h) memory for objects. A similar pattern was observed for olfactory stimuli, confirming the generality of the pattern across sensory modalities. The specificity of the behavioural deficits in Tc1 mice was confirmed using APP overexpressing mice that showed the opposite pattern of object memory deficits. In contrast to object memory, Tc1 mice showed no deficit in either immediate or long-term memory for object-in-place information. Similarly, Tc1 mice showed no deficit in short-term memory for object-location information. The latter result indicates that Tc1 mice were able to detect and react to spatial novelty at the same delay interval that was sensitive to an object novelty recognition impairment. These results demonstrate (1) that novelty detection per se and (2) the encoding of visuo spatial information was not disrupted in adult Tc1 mice. The authors conclude that the task specific nature of the short-term recognition memory deficit suggests that the trisomy of genes on human chromosome 21 in Tc1 mice impacts on (perirhinal) cortical systems supporting short-term object and olfactory recognition memory. PMID- 26868481 TI - Ultrasound-guided block of selective branches of the brachial plexus for vascular access surgery in the forearm: a preliminary report. AB - PURPOSE: The operative field for vascular access (VA) surgery in the forearm is on the volar surface, and motor nerve block is not necessary for regional anesthesia. Therefore, selective block of branches of the brachial plexus may be a more efficient anesthesia technique. METHODS: Individual nerve blocks in the axillary brachial plexus and selective blocks of the musculocutaneous and medial antebrachial cutaneous nerves in the upper arm were performed using low doses and concentrations of a local anesthetic mixture of lidocaine and ropivacaine under ultrasound (US) guidance in patients undergoing VA surgery in the forearm. The targeted nerves were identified by continuous US tracing along the upper arm to the axilla in a short-axis view. We performed three VA surgeries in the forearm using an axillary brachial plexus block and four using a selective two-nerve bock in the upper arm. We recorded any additional anesthetic requirement and evaluated intraoperative pain using the Wong-Baker Faces Pain Rating Scale (WBFRS; 0 = no pain; 10 = worst pain). RESULTS: All of the target nerve branches were clearly identified by US tracing. All patients had satisfactory intraoperative pain control (0 or 2 score on WBFRS). Four patients required small additional doses of local anesthetic. CONCLUSIONS: US-guided block of individual branches of the brachial plexus at the axilla achieved effective anesthesia using small amounts of local anesthetic. An advanced selective nerve block in the upper arm allows minimum necessary anesthesia and provides safe and efficient analgesia for VA surgery in the forearm. PMID- 26868484 TI - Corrections. PMID- 26868482 TI - Type IIIb Endoleak and Relining: A Mathematical Model of Distraction Forces. AB - PURPOSE: To examine the changes in distraction force following relining of a conventional abdominal aortic stent-graft with a type IIIb endoleak using the Nellix endovascular sealing device compared to a unilateral stent-graft. METHODS: Relining is often used to repair type IIIb endoleaks, but the consequences to graft stability are unknown. A mathematical model was constructed based on pressure and volume flow through the stent-grafts, incorporating recognized distraction force equations. Steady flow was presumed at peak systolic pressures to calculate the maximum distraction force, with gravity ignored. Distraction forces for 28- to 36-mm-diameter stent-graft bodies with 16-mm limbs were calculated and compared to forces following relining with single and double Nellix devices or the Renu unilateral device. RESULTS: Distraction forces for the 28-, 32-, and 36-mm stent-grafts prior to relining were 5.99, 10.21, and 14.99 N, respectively. Similar forces were reported after relining with bilateral Nellix devices (5.86, 10.08, and 14.86 N, respectively). However, use of a unilateral Nellix increased the distraction forces to 9.92, 14.14, and 18.92 N, respectively. These were comparable to the increase observed after relining with a Renu unilateral stent-graft (9.87, 14.09, and 18.86 N, respectively). The proportional increase in distraction force for a unilateral relining ranged from 26% to 66%, with the greatest increase noted in the smaller diameter main bodies. CONCLUSION: Relining a stent-graft with a type IIIb endoleak using bilateral Nellix devices does not increase the distraction force. However, a unilateral Nellix device or the Renu system could theoretically increase the distraction force by up to 66%, potentially risking migration and type Ia endoleak. In clinical practice, these results suggest that a relining with bilateral Nellix may have benefits over the Renu unilateral stent-graft. PMID- 26868483 TI - Malignant Melanoma Presenting as Pedunculated Lesion of the Caruncle. PMID- 26868485 TI - Corrections. PMID- 26868486 TI - Differences in Pedaling Technique in Cycling: A Cluster Analysis. AB - PURPOSE: To employ cluster analysis to assess if cyclists would opt for different strategies in terms of neuromuscular patterns when pedaling at the power output of their second ventilatory threshold (POVT2) compared with cycling at their maximal power output (POMAX). METHODS: Twenty athletes performed an incremental cycling test to determine their power output (POMAX and POVT2; first session), and pedal forces, muscle activation, muscle-tendon unit length, and vastus lateralis architecture (fascicle length, pennation angle, and muscle thickness) were recorded (second session) in POMAX and POVT2. Athletes were assigned to 2 clusters based on the behavior of outcome variables at POVT2 and POMAX using cluster analysis. RESULTS: Clusters 1 (n = 14) and 2 (n = 6) showed similar power output and oxygen uptake. Cluster 1 presented larger increases in pedal force and knee power than cluster 2, without differences for the index of effectiveness. Cluster 1 presented less variation in knee angle, muscle-tendon unit length, pennation angle, and tendon length than cluster 2. However, clusters 1 and 2 showed similar muscle thickness, fascicle length, and muscle activation. When cycling at POVT2 vs POMAX, cyclists could opt for keeping a constant knee power and pedal-force production, associated with an increase in tendon excursion and a constant fascicle length. CONCLUSIONS: Increases in power output lead to greater variations in knee angle, muscle-tendon unit length, tendon length, and pennation angle of vastus lateralis for a similar knee-extensor activation and smaller pedal-force changes in cyclists from cluster 2 than in cluster 1. PMID- 26868488 TI - Nocardioides rotundus sp. nov., isolated from deep seawater. AB - A Gram-staining-positive, aerobic, coccoid-shaped, non-motile actinobacterium, designated strain GY0594T, was isolated from deep seawater of the western Pacific. Phylogenetic analyses based on 16S rRNA gene sequences showed that this strain was affiliated with the genus Nocardioides with low 16S rRNA gene sequence similarities ( <= 96.0 %) with members of the genus Nocardioides. Chemotaxonomic characterization of strain GYP0594T supported the result of the phylogenetic analysis. The diagnostic diamino acid in the cell-wall peptidoglycan was ll-2,6 diaminopimelic acid. The major menaquinone was MK-8(H4). The polar lipids detected were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, one unidentified lipid and six unidentified phospholipids. The major cellular fatty acids were iso-C16 : 0 and C18 : 1omega9c. The DNA G+C content of strain GY0594T was determined to be 71.2 mol%. However, strain GY0594T could be distinguished from closely related species by cell morphology, nitrate reduction, aesculin hydrolysis, activity of urease, cystine arylamidase, trypsin and acid phosphatase, assimilation of N-acetylglucosamine, maltose, adipic acid, malic acid and phenylacetate, and significant differences in the proportions of several fatty acids. In conclusion, based on the data presented, strain GY0594T should be placed in the genus Nocardioides as a representative of a novel species, for which the name Nocardioides rotundus sp. nov. is proposed. The type strain is GY0594T ( = MCCC 1A10561T = KCTC 39638T). PMID- 26868487 TI - Phosphorylation Regulates Functions of ZEB1 Transcription Factor. AB - ZEB1 transcription factor is important in both development and disease, including many TGFbeta-induced responses, and the epithelial-to-mesenchymal transition (EMT) by which many tumors undergo metastasis. ZEB1 is differentially phosphorylated in different cell types; however the role of phosphorylation in ZEB1 activity is unknown. Luciferase reporter studies and electrophoresis mobility shift assays (EMSA) show that a decrease in phosphorylation of ZEB1 increases both DNA-binding and transcriptional repression of ZEB1 target genes. Functional analysis of ZEB1 phosphorylation site mutants near the second zinc finger domain (termed ZD2) show that increased phosphorylation (due to either PMA plus ionomycin, or IGF-1) can inhibit transcriptional repression by either a ZEB1 ZD2 domain clone, or full-length ZEB1. This approach identifies phosphosites that have a substantial effect regulating the transcriptional and DNA-binding activity of ZEB1. Immunoprecipitation with anti-ZEB1 antibodies followed by western analysis with a phospho-Threonine-Proline-specific antibody indicates that the ERK consensus site at Thr-867 is phosphorylated in ZEB1. In addition to disrupting in vitro DNA-binding measured by EMSA, IGF-1-induced MEK/ERK phosphorylation is sufficient to disrupt nuclear localization of GFP-ZEB1 fusion clones. These data suggest that phosphorylation of ZEB1 integrates TGFbeta signaling with other signaling pathways such as IGF-1. J. Cell. Physiol. 231: 2205-2217, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26868489 TI - The role of social determinants on tuberculosis/HIV co-infection mortality in southwest Ethiopia: a retrospective cohort study. AB - BACKGROUND: The role played by social determinants of health including social, economic, environmental and cultural factors in influencing health outcomes for many health conditions has been widely described. However, the potential impact of these factors on morbidity and mortality of infectious diseases particularly tuberculosis (Tb)/HIV co-infection mortality is scantly addressed. We assessed the role that social determinants play in Tb/HIV co-infection mortality in southwest Ethiopia. METHODS: A retrospective cohort study collated Tb and HIV data from Jimma University Teaching Hospital, Southwest Ethiopia for the period of September 2010 and August 2012. Data analysis was conducted using STATA version 14 for mackintosh. Both descriptive and inferential statistics analyses were performed. Logistic regression was applied to identify factors associated with Tb/HIV co-infection mortality at P value of <=0.05 in the final model. RESULTS: Fifty-five (20.2 %) patients died during the study period. Compared to their counterparts, more Tb/HIV co-infection death was observed in young age groups between 25 and 34 years (47.3 %), females (58.2 %), daily labors (40 %) and Muslim followers (54.5 %). 43.6 and 41.8 % of study participants respectively had single and double bedrooms, and 25.5 and 23.6 % of deceased study participants did not have water and electricity in the household respectively. Logistic regression analyses demonstrated the following factors significantly associated with Tb/HIV co-infection mortality: being a commercial sex worker (AOR, 5.6; 95 % CI, 1.2-25.8), being of bed ridden functional status (AOR, 3.9; 95 % CI, 1.5-10.3) and being a rural resident (AOR, 3.4; 95 % CI, 1.4-8.4). CONCLUSIONS: One-fifth of Tb/HIV co-infected patients died due to the co infection. Social determinants including type of occupation, severity of disease and residing in rural areas seemed to have a significant association with the poor disease outcome. Findings of this study inform the role that social determinants play in influencing mortality due to Tb/HIV co-infection. Consistent with principles of primary health care as stated by Alma Ata declaration, and in order to achieve better disease outcomes, intervention frameworks that address Tb/HIV mortality should not only focus on the medical interventions of diseases, but should also integrate and improve social determinants of affected populations. PMID- 26868491 TI - Integrated microRNA-mRNA analyses reveal OPLL specific microRNA regulatory network using high-throughput sequencing. AB - Ossification of the posterior longitudinal ligament (OPLL) is a genetic disorder which involves pathological heterotopic ossification of the spinal ligaments. Although studies have identified several genes that correlated with OPLL, the underlying regulation network is far from clear. Through small RNA sequencing, we compared the microRNA expressions of primary posterior longitudinal ligament cells form OPLL patients with normal patients (PLL) and identified 218 dysregulated miRNAs (FDR < 0.01). Furthermore, assessing the miRNA profiling data of multiple cell types, we found these dysregulated miRNAs were mostly OPLL specific. In order to decipher the regulation network of these OPLL specific miRNAs, we integrated mRNA expression profiling data with miRNA sequencing data. Through computational approaches, we showed the pivotal roles of these OPLL specific miRNAs in heterotopic ossification of longitudinal ligament by discovering highly correlated miRNA/mRNA pairs that associated with skeletal system development, collagen fibril organization, and extracellular matrix organization. The results of which provide strong evidence that the miRNA regulatory networks we established may indeed play vital roles in OPLL onset and progression. To date, this is the first systematic analysis of the micronome in OPLL, and thus may provide valuable resources in finding novel treatment and diagnostic targets of OPLL. PMID- 26868490 TI - Complications of sickle cell anaemia in children in Northwestern Tanzania. AB - OBJECTIVES: Tanzania has the third highest birth rate of sickle cell anaemia (SCA) in Africa, but few studies describe severity of complications or available treatments, especially in Northwest Tanzania around Lake Victoria where the sickle gene is most prevalent. This is a report of the spectrum of clinical disease and range of interventions available at Bugando Medical Centre (Bugando) in Northwest Tanzania in Africa. METHODS: A cross-sectional study was carried out in Bugando between 1 August 2012 and 30 September 2012. Children (<15 years old) with SCA attending Bugando were sequentially enrolled. A trained research assistant completed a Swahili questionnaire with the parent or guardian of each participant concerning demographic information, clinical features of disease, and treatments received. RESULTS: Among the 124 participants enrolled, the median age was 6 years (interquartile range [IQR] 4-8.5), and only 13 (10.5%) were < 3 years old. Almost all participants (97.6%) had a prior history of a vaso-occlusive episode, 83 (66.9%) had prior acute chest syndrome, and 21 (16.9%) had prior stroke. In the preceding 12 months, 120 (96.8%) had been hospitalized, and a vaso occlusive episode was the most common reason for hospitalization (35.5%). Prescriptions for folic acid (92.7%) and malaria prophylaxis (84.7%) were common, but only one had received a pneumococcal vaccine, and none had received hydroxyurea or prophylactic penicillin. CONCLUSION: Children with SCA receiving care in Tanzania are diagnosed late, hospitalized frequently, and have severe complications. Opportunities exist to improve care through wider access to screening and diagnosis as well as better coordination of comprehensive care. PMID- 26868492 TI - Lipids and immunoinflammatory pathways of beta cell destruction. AB - Islet inflammation contributes to beta cell demise in both type 1 and type 2 diabetes. 12-Lipoxygenase (12-LO, gene expressed as ALOX12 in humans and 12-Lo in rodents in this manuscript) produces proinflammatory metabolites such as 12(S) hydroxyeicosatetraenoic acids through dioxygenation of polyunsaturated fatty acids. 12-LO was first implicated in diabetes when the increase in 12-Lo expression and 12(S)-hydroxyeicosatetraenoic acid was noted in rodent models of diabetes. Subsequently, germline 12-Lo (-/-) was shown to prevent the development of hyperglycemia in mouse models of type 1 diabetes and in high-fat fed mice. More recently, beta cell-specific 12-Lo (-/-) was shown to protect mice against hyperglycaemia after streptozotocin and a high-fat diet. In humans, 12-LO expression is increased in pancreatic islets of autoantibody-positive, type 1 diabetic and type 2 diabetic organ donors. Interestingly, the high expression of ALOX12 is associated with the alteration in first-phase glucose-stimulated insulin secretion in human type 2 diabetic islets. To further clarify the role of islet 12-LO in diabetes and to validate 12-LO as a therapeutic target of diabetes, we have studied selective pharmacological inhibitors for 12-LO. The compounds we have identified show promise: they protect beta cell lines and human islets from apoptosis and preserve insulin secretion when challenged by proinflammatory cytokine mixture. Currently studies are underway to test the compounds in mouse models of diabetes. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied two other mini-reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x and Marc Donath, DOI: 10.1007/s00125-016-3873-z ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ). PMID- 26868493 TI - Multiple benefits of targeting inflammation in the treatment of type 2 diabetes. AB - The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x , and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ). PMID- 26868494 TI - Length of Residence and Vehicle Ownership in Relation to Physical Activity Among U.S. Immigrants. AB - Physical activity among U.S. immigrants over time is not well understood. Transportation may affect this trajectory. Using a survey of documented immigrants (N = 7240), we performed simple, then multivariable logistic regression to calculate ORs and 95 % CIs between length of residence (LOR) and both light-to-moderate (LPA) and vigorous (VPA) activity. We adjusted for demographic variables, then vehicle ownership to assess changes in ORs. Compared to new arrivals, all four LOR time-intervals were associated with lower odds of LPA and higher odds of VPA in simple analysis. All ORs for LPA remained significant after including demographics, but only one remained significant after adding vehicle ownership. Two ORs for VPA remained significant after including demographics and after adding vehicle ownership. Immigrants lower their light-to moderate activity the longer they reside in the U.S., partly from substituting driving for walking. Efforts to maintain walking for transportation among immigrants are warranted. PMID- 26868495 TI - Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy. AB - BACKGROUND: Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization. METHODS: Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values >=417 AU*min (for ADP-antagonists). RESULTS: We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17-4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20-11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52-1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59 1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62-2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63-2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99-5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28-2.29], p = 0.68). CONCLUSION: In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor. PMID- 26868496 TI - Dislocation-enhanced experimental-scale vacancy loop formation in hcp Zirconium in one single collision cascade. AB - Large defects are the main factor leading to the degradation of material properties under irradiation environments. It is commonly assumed that the large defects are mainly formed through cluster growth under continuous irradiations. Besides this mechanism, recent experiments and simulations show that sometimes an individual ion can also directly create a large defect. Here we report a novel mechanism for the formation of the large defects, as discovered by our Molecular Dynamics (MD) simulations of the collision cascades in hcp Zirconium (Zr): a pre existing edge dislocation (ED) can significantly promote the nucleation of the vacancy clusters, and even facilitate the direct formation of an experimental scale large vacancy loop (about 3 nm) in only one single displacement cascade. This dislocation-related mechanism may be the key for understanding the experimental results in the low-dose irradiated Zr where the high-density large dislocation loops are observed but difficult to be explained by the two mechanisms mentioned above. Considering that intrinsic dislocations exist in nearly all crystalline materials, our results provide a significant concept: pre existing dislocations have a strong influence on the primary damage production, and taking them into account is indispensable for assessing and improving the material's irradiation-resistance. PMID- 26868497 TI - Low-dose computed tomography for lung cancer screening: comparison of performance between annual and biennial screen. AB - OBJECTIVES: To compare the performance metrics of two different strategies of lung cancer screening by low-dose computed tomography (LDCT), namely, annual (LDCT1) or biennial (LDCT2) screen. METHODS: Recall rate, detection rate, interval cancers, sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) were compared between LDCT1 and LDCT2 arms of the MILD trial over the first seven (T0-T6; median follow-up 7.3 years) and four rounds (T0-T3; median follow-up 7.3 years), respectively. RESULTS: 1152 LDCT1 and 1151 LDCT2 participants underwent a total of 6893 and 4715 LDCT scans, respectively. The overall recall rate was higher in LDCT2 arm (6.97 %) than in LDCT1 arm (5.81 %) (p = 0.01), which was counterbalanced by the overall lower number of LDCT scans. No difference was observed for the overall detection rate (0.56 % in both arms). The two LDCT arms had similar specificity (99.2 % in both arms), sensitivity (73.5 %, in LDCT2 vs. 68.5 % in LDCT1, p = 0.62), PPV (42.4 %, in LDCT2, vs. 40.6 %, in LDCT1, p = 0.83) and NPV (99.8 %, in LDCT2 vs. 99.7 %, in LDCT1, p = 0.71). CONCLUSION: Biennial screen may save about one third of LDCT scans with similar performance indicators as compared to annual screening. KEY POINTS: * Biennial LDCT screening may be as efficient as the annual screening. * Annual and biennial LDCT screening have similar frequency of interval lung cancers. * Biennial screening may save about one third of LDCT scans. PMID- 26868499 TI - Obituary for Prof. Torsten Almen. PMID- 26868498 TI - Graph theoretical analysis reveals the reorganization of the brain network pattern in primary open angle glaucoma patients. AB - OBJECTIVES: Most previous glaucoma studies with resting-state fMRI have focused on the neuronal activity in the individual structure of the brain, yet ignored the functional communication of anatomically separated structures. The purpose of this study is to investigate the efficiency of the functional communication change or not in glaucoma patients. METHODS: We applied the resting-state fMRI data to construct the connectivity network of 25 normal controls and 25 age gender-matched primary open angle glaucoma patients. Graph theoretical analysis was performed to assess brain network pattern differences between the two groups. RESULTS: No significant differences of the global network measures were found between the two groups. However, the local measures were radically reorganized in glaucoma patients. Comparing with the hub regions in normal controls' network, we found that six hub regions disappeared and nine hub regions appeared in the network of patients. In addition, the betweenness centralities of two altered hub regions, right fusiform gyrus and right lingual gyrus, were significantly correlated with the visual field mean deviation. CONCLUSIONS: Although the efficiency of functional communication is preserved in the brain network of the glaucoma at the global level, the efficiency of functional communication is altered in some specialized regions of the glaucoma. KEY POINTS: * Global topological measures of brain network have no alterations in glaucoma patients. * Local network measures are radically reorganized in glaucoma patients. * The alterations of hub regions are found in the glaucoma. * Betweenness centrality of altered hubs may reflect the glaucoma severity. PMID- 26868500 TI - MR diagnosis of diaphragmatic endometriosis. AB - PURPOSE: To evaluate magnetic resonance imaging (MRI) for diaphragmatic endometriosis diagnosis. MATERIALS AND METHODS: Over a 2-year period, all diaphragmatic MRI performed in the context of diaphragmatic endometriosis were reviewed. Axial and coronal fat-suppressed T1- and T2-weighted sequences were analyzed by two independent readers for the presence of nodules, plaque lesions, micronodule clustering, or focal liver herniation. MR abnormalities were correlated to surgical findings in women surgically treated. Interobserver agreement was assessed by kappa statistics. RESULTS: Twenty-three women with diaphragmatic endometriosis criteria comprised the population; 14 had surgical confirmation and nine had symptoms relief with hormonal treatment. MRI sensitivity was 83 % (19/23; 95 % confidence interval [CI]: 68, 98) for reader 1 and 78 % (18/23; 95 % CI: 61, 95) for reader 2. Kappa value was 0.86 (95 % CI: 0.47, 1.00). Readers 1 and 2 detected 35 and 36 lesions, respectively, all right sided and agreed for 32 lesions on the type, location, and signal. Lesions were mostly nodules (23/32, 72 %), predominantly posterior (28/32, 87.5 %) and hyperintense on T1 (20/32, 63 %). MRI was negative for both readers in 2 surgically treated patients with small nodules or isolated diaphragmatic holes. CONCLUSION: MRI allows diaphragmatic endometriosis diagnosis with 78 to 83 % sensitivity and excellent interobserver agreement. KEY POINTS: * MRI allows the diagnosis of diaphragmatic endometriosis with up to 83 % sensitivity. * Diaphragmatic endometriosis lesions are better depicted on fat-suppressed T1 weighted sequences. * Diaphragmatic lesions, mostly hyperintense nodules, are right-sided and predominantly posterior. * MRI can help in timely diagnosis of diaphragmatic endometriosis. PMID- 26868501 TI - Tandem amino acid repeats in the green anole (Anolis carolinensis) and other squamates may have a role in increasing genetic variability. AB - BACKGROUND: Tandem amino acid repeats are characterised by the consecutive recurrence of a single amino acid. They exhibit high rates of length mutations in addition to point mutations and have been proposed to be involved in genetic plasticity. Squamate reptiles (lizards and snakes) diversify in both morphology and physiology. The underlying mechanism is yet to be understood. In a previous phylogenomic analysis of reptiles, the density of tandem repeats in an anole lizard diverged heavily from that of the other reptiles. To gain further insight into the tandem amino acid repeats in squamates, we analysed the repeat content in the green anole (Anolis carolinensis) proteome and compared the amino acid repeats in a large orthologous protein data set from six vertebrates (the Western clawed frog, the green anole, the Chinese softshell turtle, the zebra finch, mouse and human). RESULTS: Our results revealed that the number of amino acid repeats in the green anole exceeded those found in the other five species studied. Species-only repeats were found in high proportion in the green anole but not in the other five species, suggesting that the green anole had gained many amino acid repeats in either the Anolis or the squamate lineage. Since the amino acid repeat containing genes in the green anole were highly enriched in genes related to transcription and development, an important family of developmental genes, i.e., the Hox family, was further studied in a wide collection of squamates. Abundant amino acid repeats were also observed, implying the general high tolerance of amino acid repeats in squamates. A particular enrichment of amino acid repeats was observed in the central class Hox genes that are known to be responsible for defining cervical to lumbar regions. CONCLUSIONS: Our study suggests that the abundant amino acid repeats in the green anole, and possibly in other squamates, may play a role in increasing the genetic variability, and contribute to the evolutionary diversity of this clade. PMID- 26868502 TI - Factors associated with initiation of medical advanced cardiac life support after out-of-hospital cardiac arrest. AB - BACKGROUND: Termination of resuscitation rule permits to stop futile resuscitative efforts by paramedics. In a different setting, the decision to withhold resuscitation by emergency physician could be based on different factors. We aimed to identify the factors associated with the initiation of a medical ACLS in out-of-hospital cardiac arrest patients. METHODS: We prospectively collected the characteristics of all out-of hospital cardiac arrest patients occurring in a French district between March 2010 and December 2013 and managed by the emergency medical system. We analyzed the factors associated with the initiation of medical ACLS. RESULTS: Medical ACLS was initiated in 69 % of the 2690 patients included in the register. ACLS patients were younger (69 years [55-80] vs. 84 years [77-90]) and more frequently men. A higher percentage of witnessed cardiac arrest and BLS were observed. Duration of no-flow was shorter in the ACLS patients, whereas BLS duration was longer. A higher proportion of shockable rhythm and application of AED were found in this group. Mains factors associated with the initiation of medical ACLS were a suspected cardiac cause (1.73 [1.30-2.30]) and use of an automated external defibrillator (1.59 [1.18 2.16]), whereas factors associated with no medical ACLS were higher age (0.93 [0.92-0.94]), absence of BLS (0.62 [0.52-0.73]), asystole (0.31 [0.18-0.51]) and location in nursing home (0.23 [0.11-0.51]). CONCLUSIONS: The medical decision to not initiate ACLS in out-of-hospital cardiac arrest patients seems to rely on a complex combination of validated criteria used for termination of resuscitation and factors resulting from an intuitive perception of the outcome. PMID- 26868503 TI - The occlusion tests and end-expiratory esophageal pressure: measurements and comparison in controlled and assisted ventilation. AB - BACKGROUND: Esophageal pressure is used as a reliable surrogate of the pleural pressure. It is conventionally measured by an esophageal balloon placed in the lower part of the esophagus. To validate the correct position of the balloon, a positive pressure occlusion test by compressing the thorax during an end expiratory pause or a Baydur test obtained by occluding the airway during an inspiratory effort is used. An acceptable catheter position is defined when the ratio between the changes in esophageal and airway pressure (?Pes/?Paw) is close to unity. Sedation and paralysis could affect the accuracy of esophageal pressure measurements. The aim of this study was to evaluate, in mechanically ventilated patients, the effects of paralysis, two different esophageal balloon positions and two PEEP levels on the ?Pes/?Paw ratio measured by the positive pressure occlusion and the Baydur tests and on the end-expiratory esophageal pressure and respiratory mechanics (lung and chest wall). METHODS: Twenty-one intubated and mechanically ventilated patients (mean age 64.8 +/- 14.0 years, body mass index 24.2 +/- 4.3 kg/m(2), PaO2/FiO2 319.4 +/- 117.3 mmHg) were enrolled. In step 1, patients were sedated and paralyzed during volume-controlled ventilation, and in step 2, they were only sedated during pressure support ventilation. In each step, two esophageal balloon positions (middle and low, between 25-30 cm and 40-45 cm from the mouth) and two levels of PEEP (0 and 10 cmH2O) were applied. The ?Pes/?Paw ratio and end-expiratory esophageal pressure were evaluated. RESULTS: The ?Pes/?Paw ratio was slightly higher (+0.11) with positive occlusion test compared with Baydur's test. The level of PEEP and the esophageal balloon position did not affect this ratio. The ?Pes and ?Paw were significantly related to a correlation coefficient of r = 0.984 during the Baydur test and r = 0.909 in the positive occlusion test. End-expiratory esophageal pressure was significantly higher in sedated and paralyzed patients compared with sedated patients (+2.47 cmH2O) and when esophageal balloon was positioned in the low position (+2.26 cmH2O). The esophageal balloon position slightly influenced the lung elastance, while the PEEP reduced the chest wall elastance without affecting the lung and total respiratory system elastance. CONCLUSIONS: Paralysis and balloon position did not clinically affect the measurement of the ?Pes/?Paw ratio, while they significantly increased the end-expiratory esophageal pressure. PMID- 26868504 TI - The safety and efficacy of AphtoFix(r) mouth ulcer cream in the management of recurrent aphthous stomatitis. AB - BACKGROUND: Recurrent Aphthous stomatitis (RAS) is a prevalent ulcerative and painful disorder of the oral cavity with unknown etiology and for which no efficient treatment is currently available. The present study aimed to evaluate the safety and the efficacy of AphtoFix(r), a new mouth ulcer cream that was developed to help treat RAS. Prior to launching the product on the market, two initial safety assessment studies were performed. SUBJECTS AND METHODS: In a first study, the in vitro biocompatibility of AphtoFix(r) was evaluated on reconstructed human gingival tissue models according to ISO guidelines 10993. In a second study, the tolerability of AphtoFix(r) was evaluated in 20 subjects during a 4-weeks daily application in the mouth. The third study investigated both the safety and efficacy of AphtoFix(r) treatment on 19 patients suffering from RAS. This study was done in compliance with the Helsinki Declaration. RESULTS: The results of in vitro biocompatibility study showed that AphtoFix(r) mouth ulcer cream did not induce any detectable cytotoxicity and irritation. These observations were confirmed in the 4 weeks tolerability study where no undesired of adverse reactions were noticed. The results of the post-market clinical efficacy study demonstrated a clear reduction in ulcer size from baseline after 3 days treatment (p < 0.05). Pain intensity reduction was also observed in all subjects. CONCLUSION: The application of AphtoFix(r) did not induce any undesired skin or mucosa reactions. These initial findings demonstrate that AphtoFix(r) is safe and efficient in reducing ulcer size and decreasing the pain intensity induced by ulcers. TRIAL REGISTRATION: Clinical trial Registry India Nr. CTRI201408004918 , Date of registration: 22/08/2014. PMID- 26868505 TI - Erratum to: Potassium urinary excretion and dietary intake: a cross-sectional analysis in 8-10 year-old children. PMID- 26868506 TI - Lysosomal recruitment of TSC2 is a universal response to cellular stress. AB - mTORC1 promotes cell growth and is therefore inactivated upon unfavourable growth conditions. Signalling pathways downstream of most cellular stresses converge on TSC1/2, which serves as an integration point that inhibits mTORC1. The TSC1/2 complex was shown to translocate to lysosomes to inactivate mTORC1 in response to two stresses: amino-acid starvation and growth factor removal. Whether other stresses also regulate TSC2 localization is not known. How TSC2 localization responds to combinations of stresses and other stimuli is also unknown. We show that both amino acids and growth factors are required simultaneously to maintain TSC2 cytoplasmic; when one of the two is missing, TSC2 relocalizes to lysosomes. Furthermore, multiple different stresses that inhibit mTORC1 also drive TSC2 lysosomal accumulation. Our findings indicate that lysosomal recruitment of TSC2 is a universal response to stimuli that inactivate mTORC1, and that the presence of any single stress is sufficient to cause TSC2 lysosomal localization. PMID- 26868508 TI - RVX-208, a BET-inhibitor for treating atherosclerotic cardiovascular disease, raises ApoA-I/HDL and represses pathways that contribute to cardiovascular disease. AB - High density lipoproteins (HDL), through activity of the main protein component apolipoprotein A-I (ApoA-I), can reduce the risk of cardiovascular disease (CVD) by removing excess cholesterol from atherosclerotic plaque. In this study, we demonstrate that the bromodomain and extraterminal domain (BET) inhibitor RVX-208 increases ApoA-I gene transcription and protein production in human and primate primary hepatocytes. Accordingly, RVX-208 also significantly increases levels of ApoA-I, HDL-associated cholesterol, and HDL particle number in patients who received the compound in recently completed phase 2b trials SUSTAIN and ASSURE. Moreover, a post-hoc analysis showed lower instances of major adverse cardiac events in patients receiving RVX-208. To understand the effects of RVX-208 on biological processes underlying cardiovascular risk, we performed microarray analyses of human primary hepatocytes and whole blood treated ex vivo. Overall, data showed that RVX-208 raises ApoA-I/HDL and represses pro-inflammatory, pro atherosclerotic and pro-thrombotic pathways that can contribute to CVD risk. PMID- 26868507 TI - Effects of simvastatin, ezetimibe and simvastatin/ezetimibe on mitochondrial function and leukocyte/endothelial cell interactions in patients with hypercholesterolemia. AB - BACKGROUND: Cholesterol-lowering therapy has been related with several beneficial effects; however, its influence on oxidative stress and endothelial function is not fully elucidated. AIMS: To investigate the effect of simvastatin and ezetimibe on mitochondrial function and leukocyte-endothelium interactions in polymorphonuclear cells of hyperlipidemic patients. METHODS: Thirty-nine hyperlipidemic patients were randomly assigned to one of two groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4 week period. Lipid profile, mitochondrial parameters (oxygen consumption, reactive oxygen species (ROS) and membrane potential), glutathione levels, superoxide dismutase activity, catalase activity and leukocyte/endothelial cell interactions and adhesion molecules -VCAM-1, ICAM-1, E-selectin, were evaluated. RESULTS: An improvement in lipid profile was observed after administration of simvastatin or ezetimibe alone (LDLc: -40.2 vs -19.6%, respectively), though this effect was stronger with the former (p < 0.001), and a further reduction was registered when the two were combined (LDLc: -50.7% vs -56.8%, respectively). In addition to this, simvastatin, ezetimibe and simvastatin + ezetimibe significantly increased oxygen consumption, membrane potential and glutathione content, and decreased levels of ROS, thereby improving mitochondrial function. Furthermore, simvastatin + ezetimibe increased catalase activity. In addition, simvastatin and simvastatin/ezetimibe improved leukocyte/endothelium interactions by decreasing leukocyte rolling and adhesion and increasing leukocyte rolling velocity. Finally, simvastatin, ezetimibe and simvastatin + ezetimibe reduced levels of the adhesion molecule ICAM-1, and ezetimibe + simvastatin significantly decreased levels of E-selectin. CONCLUSION: Co-administration of simvastatin and ezetimibe has an additive cholesterol-lowering effect and beneficial consequences for mitochondrial function and leukocyte/endothelium interactions in leukocytes of hypercholesterolemic patients. PMID- 26868509 TI - High triglyceride levels alter the correlation of apolipoprotein B with low- and non-high-density lipoprotein cholesterol mostly in individuals with diabetes or metabolic syndrome. AB - OBJECTIVE: To assess the correlation of Apolipoprotein B (Apo-B) with low-density (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) in untreated individuals attending a lipid clinic. METHODS: This was a retrospective study conducted in Greece and including 1000 dyslipidemic subjects. We included individuals not taking lipid-lowering therapy at baseline visit and divided them in 2 groups: subjects diagnosed with diabetes or fulfilling the criteria of metabolic syndrome (MetS) and hyperlipidemic subjects without diabetes or MetS. The correlations (r(2)) of Apo-B with LDL-C and non-HDL-C were assessed in these 2 groups. Further analyses were performed according to the baseline triglyceride (TG) levels (=200 mg/dL). RESULTS: From 821 eligible subjects, 51% were diagnosed with diabetes or MetS. The correlations between Apo-B and LDL-C or non HDL-C were similar for the individuals with TG < 200 mg/dL. Specifically, Apo-B was significantly correlated with LDL-C (r(2) = 0.755, p < 0.01, for those with diabetes or MetS; r(2) = 0.848, p < 0.01, for non-diabetic and no MetS hyperlipidemic subjects). The corresponding correlations between Apo-B and non HDL-C for the 2 groups were 0.743 and 0.838, respectively (p < 0.01). Although these correlations remained significant for the individuals with high TG levels (>=200 mg/dL), the correlation factor was markedly decreased mostly in those with diabetes or MetS (r(2) = 0.600, p < 0.01, for the correlation between Apo-B and LDL-C; r(2) = 0.604, p < 0.01, for the correlation between Apo-B and non-HDL-C); in contrast, the corresponding correlations were stronger in the non-diabetic and no MetS hyperlipidemic individuals (r(2) = 0.710 and 0.714, respectively, p < 0.01). CONCLUSION: Apo-B correlation with both LDL-C and non-HDL-C is reduced in individuals with high TG levels and in particular for those with diabetes or MetS. PMID- 26868510 TI - The Carnitine-butyrobetaine-trimethylamine-N-oxide pathway and its association with cardiovascular mortality in patients with carotid atherosclerosis. AB - BACKGROUND AND PURPOSE: gamma-butyrobetaine (gammaBB) is a metabolite from dietary Carnitine, involved in the gut microbiota-dependent conversion from Carnitine to the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO). Orally ingested gammaBB has a pro-atherogenic effect in experimental studies, but gammaBB has not been studied in relation to atherosclerosis in humans. The aim of this study was to evaluate associations between serum levels of gammaBB, TMAO and their common precursors Carnitine and trimethyllysine (TML) and carotid atherosclerosis and adverse outcome. METHODS: Serum gammaBB, Carnitine, TML and TMAO were quantified by high performance liquid chromatography in patients with carotid artery atherosclerosis (n = 264) and healthy controls (n = 62). RESULTS: Serum gammaBB (p = 0.024) and Carnitine (p = 0.001), but not TMAO or TML, were increased in patients with carotid atherosclerosis. Higher levels of gammaBB and TML, but not TMAO or Carnitine were independently associated with cardiovascular death also after adjustment for age and eGFR (adjusted HR [95%] 3.3 [1.9-9.1], p = 0.047 and 6.0 [1.8-20.34], p = 0.026, respectively). CONCLUSIONS: Patients with carotid atherosclerosis had increased serum levels of gammaBB, and elevated levels of gammaBB and its precursor TML were associated with cardiovascular mortality. Long-term clinical studies of gammaBB, as a cardiovascular risk marker, and safety studies regarding dietary supplementation of gammaBB, are warranted. PMID- 26868511 TI - Thrombospondin-4 ablation reduces macrophage recruitment in adipose tissue and neointima and suppresses injury-induced restenosis in mice. AB - OBJECTIVE: Thrombospondin-4 (Thbs4) is a member of the extracellular calcium binding protein family and is linked to cell adhesion and migration. Given the involvement of Thbs4 in vascular inflammation, we hypothesized that Thbs4 plays a role in restenosis. METHODS AND RESULTS: Here we show evidence that Thbs4 is upregulated in wire-injured mouse arteries and correlated with CD68 expression. Macrophage infiltration is reduced in both adipose tissue (AT) and neointima of Thbs4/ApoE double knockout (DKO) mice after injury. Moreover, Thbs4 deficiency prevents restenosis in ApoE KO mice fed a Western-type diet (WTD). Lethally irradiated DKO mice that receive bone marrow from ApoE KO or DKO mice have reduced neointima development. While considering related mechanisms, we note decreased chemokine production in both AT and neointima of DKO mice. In addition, vascular smooth muscle cells (VSMCs) derived from DKO mice display suppressed proliferation and migration in comparison with controls. Thioglycollate (TG) induced macrophages from DKO mice show retarded adhesion to VSMCs. Recombinant Thbs4 promoted macrophage adhesion to VSMCs, and enhanced VSMC proliferation and migration. CONCLUSION: Collectively, these data highlight the significance of Thbs4 in regulating macrophage accumulation and treating restenosis. PMID- 26868513 TI - Enhancing Self-Determination in Health: Results of an RCT of the Ask Project, a School-Based Intervention for Adolescents with Intellectual Disability. AB - BACKGROUND: Adolescents with intellectual disability have high levels of unrecognized disease and inadequate health screening/promotion which might be addressed by improving health advocacy skills. METHODS: A parallel-group cluster randomized controlled trial was conducted to investigate whether a health intervention package, consisting of classroom-based health education, a hand-held health record and a health check, increased carer-reported health advocacy in adolescents with intellectual disabilities. RESULTS: Carers of 388 adolescents responded. Adolescents allocated to receive the health intervention package were significantly more likely to go to the doctor on their own, ask questions and explain their health problems to the doctor without help. Carers reported their adolescent had benefited, gaining increased knowledge and responsibility for their own health. They themselves reported an increase in knowledge and better ability to support the young person. CONCLUSIONS: An educational initiative based on the Ask Health Diary led to improved healthcare autonomy for adolescents with intellectual disabilities. PMID- 26868512 TI - Low carotid artery wall shear stress is independently associated with brain white matter hyperintensities and cognitive impairment in older patients. AB - BACKGROUND & AIMS: Brain white-matter lesions and cognitive impairment are increasing because of the increasing number of patients aged >=80 y. Wall shear stress (WSS) plays a pivotal role as a fluid mechanical mediator in vascular reactivity and atherosclerosis. In this study, we investigated the associations among common carotid artery (CCA) WSS, white-matter lesions, and cognitive impairment in patients aged >=80 y METHODS: We enrolled 384 patients aged >=80 y. All subjects had CCA-WSS, brain white-matter hyperintensities (WMH), and Mini Mental State Examination (MMSE) assessments and were divided into three groups using tertiles of mean and peak CCA-WSS. RESULTS: For groups classified by the tertile of mean CCA-WSS, WMH, and WMH fraction were decreased; the MMSE score increased from low to high in the respective groups. Differences in WMH, WMH fraction, and the MMSE score were significant between any two groups (all adjusted p < 0.001). Groups classified by the tertile of peak CCA-WSS had the same pattern. Mean and peak CCA-WSS were significantly and inversely correlated with WMH (r = -0.575 and -0.570, respectively; p < 0.001) and WMH fraction (r = 0.574 and -0.569, respectively; p < 0.001) but positively correlated with the MMSE score (r = 0.390 and 0.278, respectively; p < 0.001). Multiple linear backward stepwise regression indicated the mean and peak CCA-WSS were significantly and independently associated with WMH, WMH fraction, and the MMSE score (all adjusted p < 0.001). CONCLUSION: Carotid artery WSS was independently associated with brain white-matter lesions and cognitive impairment in patients aged >=80 y. PMID- 26868514 TI - Current indications for the Hartmann procedure. AB - The Hartmann procedure is used in the case of left-sided colonic disease, especially in the setting of emergency where intraoperative conditions contraindicate completion of an anastomosis. This procedure has been initially described for the management of colorectal cancer and is based on a sigmoidectomy without restoration of intestinal continuity, including a left-sided iliac terminal stoma and closure of the rectal stump. Both procedure and underlying risk factors explain high rates of mortality and morbidity, around 15 and 50% respectively, and a low overall rate of subsequent restoration of internal continuity, less than 50%. The purpose of this review was to evaluate the value of the Hartmann procedure and its equivalents in colonic surgery, according to its indications: colorectal cancer, peritonitis from diverticular disease, anastomotic complications, ischemic colitis, left-sided colonic volvulus and abdominal trauma. PMID- 26868515 TI - Free fatty acids, not triglycerides, are associated with non-alcoholic liver injury progression in high fat diet induced obese rats. AB - BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD), commonly associated with obesity and metabolic syndrome, is increasing worldwide. However, the specific mechanisms that mediate the progression from simple steatosis to non alcoholic steatohepatitis remain largely unclear. This study aimed to investigate the time dependent changes of triglyceride (TG) and free fatty acid (FFA) levels in the blood and liver over 24 weeks in high-fat diet-induced obese rats with NAFLD and to clarify the role of high FFA levels in the progression of liver injury. METHODS: Male Wistar rats were randomly divided into three groups (n = 30 per group): the Control group, fed standard chow; the High-fat diet (HFD) group, fed high-fat chow; and the Acipimox group, fed an HFD plus acipimox (100 mg/kg/d, ig) for 8, 16 and 24 weeks. After treatment, blood and liver samples were collected for biochemical analyses, western blotting analysis and a histopathological study. RESULTS: The visceral fat/weight and liver/body weight ratios were higher in both the HFD and Acipimox groups than in the Control group. The TG and FFA concentrations in blood and liver were increased in the HFD group and associated with elevated serum alanine aminotransferase (ALT) and liver malondialdehyde (MDA) levels and macro/microvesicular steatosis on hepatic fragments. Although the TG levels in the liver were similar between the HFD and Acipimox groups (p > 0.05), the FFA concentrations in the blood and liver were much lower in the latter group (p < 0.05). The Acipimox group showed normal ALT and MDA levels as well as less severe hepatic histological changes than did the HFD group (NAFLD activity score: 2.14 +/- 0.14, 2.43 +/- 0.20 and 2.63 +/- 0.26 at 8, 16 and 24 weeks, respectively; p < 0.05 versus the HFD group at 24 weeks). The diacylglycerol acyltransferase 2 (DGAT2) protein levels were similar between the HFD and Acipimox groups (p > 0.05), but the protein expression level of carnitine palmitoyltransferase 1a (CPT-1a) was higher in the Acipimox group. CONCLUSIONS: Liver TG accumulation does not cause cellular injury in the liver; rather, FFAs or their metabolites are responsible for liver injury via increased oxidative stress. It is suggested that the therapeutic efforts to prevent non alcoholic liver injury progression should be focused on reducing the burden of fatty acids transported to the liver or those being synthesized in the liver. PMID- 26868516 TI - A Case of Sepsis in a 92-Year-Old Korean Woman Caused by Aerococcus urinae and Identified by Sequencing the 16S Ribosomal RNA Gene. AB - Aerococcus urinae is an uncommon pathogen that was first identified in 1992. Herein, we report a case of bloodstream infection caused by A. urinae, which occurred in a 92-year-old Korean female patient with an underlying urologic infection who had altered consciousness. The blood culture yielded positive results for A. urinae; however, identifying A. urinae was challenging. Ultimately, we used 16S ribosomal RNA (rRNA) gene sequencing to identify the organism. The patient recovered after being treated with ertapenem and meropenem. To our knowledge, this is the first report of a case of A. urinae sepsis in South Korea. PMID- 26868517 TI - Concentration of MS2 phage in river water by a combined ferric colloid adsorption and foam separation-based method, with MS2 phage leaching from ferric colloid. AB - The concentration of MS2 phage as a model RNA virus in river water using a combined ferric colloid adsorption and foam separation-based method was examined. The MS2 phage concentrations were determined by the plaque-forming unit (PFU) method and reverse transcription quantitative PCR (RT-qPCR) analysis. When ferric colloid adsorption was performed prior to foam separation, MS2 phage was effectively removed from river water and concentrated in the generated foam within 7 min. The removal efficiency was >99% at the optimum iron and casein concentrations of 5 mg-Fe/L and 10 mg/L, respectively. Furthermore, based on the analysis of the collected ferric colloid dissolved using deferoxamine, the MS2 concentration in the colloid-dissolved solution was 190-fold higher than that found in raw water according to RT-qPCR analysis. This is a novel method for concentrating RNA viruses to facilitate their detection in river water using coagulation and foam separation combined with chelate dissolution of ferric flocs. PMID- 26868518 TI - Re-characterization of mono-2-ethylhexyl phthalate hydrolase belonging to the serine hydrolase family. AB - A novel bacterium assimilating di-2-ethylhexyl phthalate as a sole carbon source was isolated, and identified as a Rhodococcus species and the strain was named EG 5. The strain has a mono-2-ethylhexyl phthalate (MEHP) hydrolase (EG-5 MehpH), which exhibits some different enzymatic features when compared with the previously reported MEHP hydrolase (P8219 MehpH) from Gordonia sp. These differences include different pH optimum activity, maximal reaction temperature and heat stability. The Km and Vmax values of EG-5 MehpH were significantly higher than those of P8219 MehpH. The primary structure of EG-5 MehpH showed the highest sequence identity to that of P8219 MehpH (39%) among hydrolases. The phylogenetic tree suggested that EG-5 MehpH and P8219 MehpH were categorized in different groups of the novel MEHP hydrolase family. Mutation of a conserved R(109) residue of EG-5 MehpH to a hydrophobic residue resulted in a dramatic reduction in the Vmax value towards MEHP without affecting the Km value. These results indicate that this residue may neutralize the negative charge of a carboxylate anion of MEHP, and thus inhibit the catalytic nucleophile from attacking the ester bond. In other words, the R residue blocks inhibition from the carboxylate anion of MEHP. Recently, registered hypothetical proteins exhibiting 98% or 99% identities for EG-5 MehpH or for P8219 MehpH were found from some pathogens belonging to Actinomycetes. The protein may have other activities besides MEHP hydrolysis and function in other physiological reactions in some Actinomycetes. PMID- 26868519 TI - A comparison of clinicopathological characteristics and long-term survival outcomes between symptomatic and screen-detected breast cancer in Japanese women. AB - BACKGROUND: Several studies from other countries have reported that patients with screen-detected breast cancer have better survival than those with symptomatic breast cancer. However, no such comparison has been performed in Japan. Therefore, we aimed to compare the clinicopathological characteristics and survival rates between symptomatic and screen-detected breast cancer in Japanese women. METHODS: From January 2000 to December 2004, 977 and 182 women with symptomatic or screen-detected breast cancer, respectively, underwent surgery at a single Japanese hospital. We retrospectively reviewed these patients' clinicopathological data. Likelihood of death was estimated using the Kaplan Meier method and the log-rank test. Multivariate analysis including mode of detection, tumor size, lymph node status, hormone receptor status, and adjuvant therapy administration was performed using the Cox proportional hazards model. RESULTS: Screen-detected breast cancer was associated with increased rate of breast-conserving surgery, non-invasive carcinoma, smaller tumor size, decreased lymph node involvement, increased hormone receptor positivity, and decreased adjuvant chemotherapy administration. Compared to women with symptomatic tumors, those with screen-detected tumors had improved overall and breast cancer-specific survival rates. Factors associated with survival in univariate analysis were screen detection, tumor size, lymph node status, progesterone receptor status, and adjuvant chemotherapy administration. CONCLUSIONS: Breast cancer screening in Japanese women has led to increases in the rates of breast-conserving surgery, hormone receptor positivity, and survival rates along with reductions in axillary lymph node dissection and adjuvant chemotherapy administration. PMID- 26868520 TI - Choosing between intraoral or extraoral, red or infrared laser irradiation after impacted third molar extraction. AB - BACKGROUND AND OBJECTIVE: Swelling and trismus are complications experienced by nearly all subjects after undergoing oral surgery for the removal of impacted teeth. The main purpose of this paper was to compare the effects of photobiomodulation therapy (PBMT) at two different wavelengths applied intra orally and extra-orally on facial swelling and trismus in the postoperative period following the extraction of impacted mandibular third molars. STUDY DESIGN/MATERIALS AND METHODS: Sixty subjects were randomly divided into five groups, taking into account the type of laser therapy applied after surgery (intraoral or extraoral irradiation with 660 nm laser; intraoral or extraoral irradiation with 808 nm; and sham irradiation). Two and seven days after the surgery, two blinded evaluators measured the subjects' faces (swelling), and mouth opening (trismus). RESULTS: There was a statistically significant interaction between the irradiation site and wavelength (swelling and trismus were smaller if the red laser was applied intra-orally or if infrared laser was applied extra-orally). The intra-group analyses showed that 808 nm laser applied extra-orally favored reductions in postoperative facial swelling and trismus, although the inter-group comparisons revealed no statistically significant differences. CONCLUSION: Besides energy parameters, the combination of irradiation site and wavelength drive the results of phototherapy after the removal of impacted teeth. Lasers Surg. Med. 48:511-518, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26868522 TI - Autosomal dominant polycystic kidney disease. PMID- 26868521 TI - Does primary neoadjuvant systemic therapy eradicate minimal residual disease? Analysis of disseminated and circulating tumor cells before and after therapy. AB - BACKGROUND: Patients with breast cancer (BC) undergoing neoadjuvant chemotherapy (NACT) may experience metastatic relapse despite achieving a pathologic complete response. We analyzed patients with BC before and after NACT for disseminated tumor cells (DTCs) in the bone marrow(BM); comprehensively characterized circulating tumor cells (CTCs), including stem cell-like CTCs (slCTCs), in blood to prove the effectiveness of treatment on these cells; and correlated these findings with response to therapy, progression-free survival (PFS), and overall survival (OS). METHODS: CTCs (n = 135) and slCTCs (n = 91) before and after NACT were analyzed using the AdnaTest BreastCancer, AdnaTest TumorStemCell, and epithelial-mesenchymal transition (QIAGEN Hannover GmbH Germany). The expression of estrogen receptor, progesterone receptor, and the resistance marker excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), nuclease were studied in separate single-plex reverse transcription polymerase chain reaction experiments. DTCs were evaluated in 142 patients before and 165 patients after NACT using the pan-cytokeratin antibody A45-B/B3 for immunocytochemistry. RESULTS: The positivity rates for DTCs, CTCs, and slCTCs were 27 %, 24 %, and 51 % before and 20 %, 8 %, and 20 % after NACT, respectively. Interestingly, 72 % of CTCs present after therapy were positive for ERCC1, and CTCs before (p = 0.005) and after NACT (p = 0.05) were significantly associated with the presence of slCTCs. Whereas no significant associations with clinical parameters were found for CTCs and slCTCs, DTCs were significantly associated with nodal status (p = 0.03) and histology (0.046) before NACT and with the immunohistochemical subtype (p = 0.02) after NACT. Univariable Cox regression analysis revealed that age (p = 0.0065), tumor size before NACT (p = 0.0473), nodal status after NACT (p = 0.0137), and response to NACT (p = 0.0136) were significantly correlated with PFS, whereas age (p = 0.0162) and nodal status after NACT (p = 0.0243) were significantly associated with OS. No significant correlations were found for DTCs or any CTCs before and after therapy with regard to PFS and OS. CONCLUSIONS: Although CTCs were eradicated more effectively than DTCs, CTCs detected after treatment seemed to be associated with tumor cells showing tumor stem cell characteristics as well as with resistant tumor cell populations that might indicate a worse outcome in the future. Thus, these patients might benefit from additional second-line treatment protocols including bisphosphonates for the eradication of DTCs. PMID- 26868523 TI - Seed heteromorphism in Triticum dicoccoides: association between seed positions within a dispersal unit and dormancy. AB - Variation in seed size and dormancy can take the form of seed heteromorphism, i.e., production of different kinds of seeds by a single individual. In this paper, I tested for the effect of seed position within a spikelet on its germination over time, and the contribution of this effect to population differentiation along an aridity gradient in an annual grass, Triticum dicoccoides. The results show that the upper grain in a spikelet is larger than the bottom grain, and either germinates in the season following dispersal, or dies. In contrast, a substantial fraction of the bottom grains do not germinate in the first season, but remain dormant in the soil seed bank for 1 and, very rarely, 2 years. This pattern was observed in seeds of all origins, but the bottom grains from the most arid location had the lowest, and from the least arid location, the highest germination fraction in the 1st year and vice versa in the 2nd year. This difference in germination fraction was observed under controlled irrigation conditions but not in the field experiment. These mixed results suggest that seed dimorphism is a life history trait with a complicated evolutionary history and wide adaptive implications. Seed dimorphism in T. dicoccoides could initially be an adaptation for reducing competition in productive (i.e., high precipitation) environments. In addition to this, seed dimorphism under increasing aridity could become a bet-hedging trait allowing a population to survive periods of insufficient rainfall through dormancy. PMID- 26868524 TI - Living on the edge: adaptive and plastic responses of the tree Nothofagus pumilio to a long-term transplant experiment predict rear-edge upward expansion. AB - Current climate change affects the competitive ability and reproductive success of many species, leading to local extinctions, adjustment to novel local conditions by phenotypic plasticity or rapid adaptation, or tracking their optima through range shifts. However, many species have limited ability to expand to suitable areas. Altitudinal gradients, with abrupt changes in abiotic conditions over short distances, represent "natural experiments" for the evaluation of ecological and evolutionary responses under scenarios of climate change. Nothofagus pumilio is the tree species which dominates as pure stands the montane forests of Patagonia. We evaluated the adaptive value of variation in quantitative traits of N. pumilio under contrasting conditions of the altitudinal gradient with a long-term reciprocal transplant experimental design. While high elevation plants show little response in plant, leaf, and phenological traits to the experimental trials, low-elevation ones show greater plasticity in their responses to changing environments, particularly at high elevation. Our results suggest a relatively reduced potential for evolutionary adaptation of high elevation genotypes, and a greater evolutionary potential of low-elevation ones. Under global warming scenarios of forest upslope migration, high-elevation variants may be outperformed by low-elevation ones during this process, leading to the local extinction and/or replacement of these genotypes. These results challenge previous models and predictions expected under global warming for altitudinal gradients, on which the leading edge is considered to be the upper treeline forests. PMID- 26868526 TI - Head-on collision and overtaking collision between an envelope solitary wave and a KdV solitary wave in a dusty plasma. AB - Head-on collision and overtaking collision between a KdV solitary wave and an envelope solitary wave are first studied in present paper by using Particle-in cell (PIC) method in a dusty plasma. There are phase shifts of the KdV solitary wave in both head-on collision and the overtaking collision, while no phase shift is found for the envelop solitary wave in any cases. The remarkable difference between head-on collision and the overtaking collision is that the phase shift of KdV solitary wave increases as amplitude of KdV solitary wave increases in head on collision, while it decreases as amplitude of the KdV solitary wave increases in the overtaking collision. It is found that the maximum amplitude during the collision process is less than sum of two amplitudes of both solitary waves, but is larger than either of the amplitude. PMID- 26868525 TI - Macrophage migration inhibitory factor drives neutrophil accumulation by facilitating IL-1beta production in a murine model of acute gout. AB - This study evaluated the role of macrophage migration inhibitory factor in inflammation caused by monosodium urate crystals. The concentration of macrophage migration inhibitory factor was increased in synovial fluid of patients with acute gout, and there was a positive correlation between intra-articular macrophage migration inhibitory factor and IL-1beta concentrations. In mice, the injection of monosodium urate crystals into the knee joint increased the levels of macrophage migration inhibitory factor in macrophages and in inflamed tissue. The injection of recombinant macrophage migration inhibitory factor into the joint of mice reproduced the inflammatory response observed in acute gout, including histologic changes, the recruitment of neutrophils, and increased levels of IL-1beta and CXCL1. Importantly, the accumulation of neutrophils and the amount IL-1beta in the joints were reduced in macrophage migration inhibitory factor-deficient mice when injected with monosodium urate crystals. We observed a similar effect when we blocked macrophage migration inhibitory factor with (S,R) 3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid or anti-macrophage migration inhibitory factor. In addition, the blockade of IL-1R and CXCR2 reduced recombinant macrophage migration inhibitory factor-induced neutrophil recruitment. Mechanistically, recombinant macrophage migration inhibitory factor is important for the synthesis of il1beta mRNA in vivo and in isolated macrophages. Altogether, macrophage migration inhibitory factor promotes neutrophil accumulation and is important for IL-1beta production, which are 2 crucial events contributing to the pathogenesis of acute gout. PMID- 26868527 TI - [Nitrofurantoine, recommendations to be followed to reduce severe complications occurency risk]. PMID- 26868529 TI - Financial incentives, timing of births, and infant health: a closer look into the delivery room. AB - As a result of strong financial incentives created by the German parental leave reform on January 1, 2007, some 1000 births have been shifted from the last days of 2006 to the first days of 2007, especially by working mothers. This fact is already described in the literature, yet there is no evidence as to the mechanisms and only scarce evidence regarding the effects on newborn health. I use new data to study the timing of C-sections and the induction of births around the day the reform took effect. I estimate that postponed C-sections and inductions account for nearly 80 % of the pre-reform shortfall and nearly 90 % of the post-reform excess number of births. Despite concerns voiced by doctors before the reform, hardly any evidence can be found for detrimental health effects of those shifts, as measured by changes in gestational age, birth weight, APGAR scores, neonatal mortality, or hospitalization. PMID- 26868528 TI - Sclerostin antibody prevented progressive bone loss in combined ovariectomized and concurrent functional disuse. AB - Osteoporosis is characterized by low bone mass and compromised trabecular architecture, and is commonly occurred in post-menopausal women with estrogen deficiency. In addition, prolonged mechanical unloading, i.e., long term bed rest, can exaggerate the bone loss. Sclerostin is a Wnt signaling antagonist and acts as a negative regulator for bone formation. A sclerostin-neutralizing antibody (Scl-Ab) increased bone mineral density in women with postmenopausal osteoporosis and healthy men. The objective of this study was to characterize the condition of bone loss in ovariectomized (OVX) rats with concurrent mechanical unloading and evaluate the effect of sclerostin antibody treatment in mitigating the prospective severe bone loss conditions in this model. Four-month-old OVX- or sham-operated female SD rats were used in this study. They were subjected to functional disuse induced by hind-limb suspension (HLS) or free ambulance after 2days of arrival. Subcutaneous injections with either vehicle or Scl-Ab at 25mg/kg were made twice per week for 5weeks from the time of HLS. MUCT analyses demonstrated a significant decrease in distal metaphyseal trabecular architecture integrity with HLS, OVX and HLS+OVX (bone volume fraction decreased by 29%, 71% and 87% respectively). The significant improvements of various trabecular bone parameters (bone volume fraction increased by 111%, 229% and 297% respectively as compared with placebo group) with the administration of Scl-Ab are associated with stronger mechanical property and increased bone formation by histomorphometry. These results together indicate that Scl-Ab prevented the loss of trabecular bone mass and cortical bone strength in OVX rat model with concurrent mechanical unloading. The data suggested that monoclonal sclerostin neutralizing antibody represents a promising therapeutic approach for severe osteoporosis induced by estrogen deficiency with concurrent mechanical unloading. PMID- 26868530 TI - An Investigation of the Behavior of Solvent based Polycaprolactone ink for Material Jetting. AB - An initial study of processing bioresorbable polycaprolactone (PCL) through material jetting was conducted using a Fujifilm Dimatix DMP-2830 material printer. The aim of this work was to investigate a potential solvent based method of jetting polycaprolactone. Several solvents were used to prepare a PCL solvent based ink and 1, 4-dioxane was chosen with the consideration of both solubility and safety. The morphology of PCL formed under different substrate temperatures, droplet spacings were investigated. Multi-layer PCL structures were printed and characterized. This work shows that biodegradable polycaprolactone can be processed through material jetting. PMID- 26868532 TI - Optic neuropathy secondary to syphilis in an HIV negative patient. AB - Ocular syphilis is a resurgent clinical condition due to unsafe sexual practices. It has been reported in both immunocompromised and immunocompetent patients, but in HIV positive patients, it is more likely to exhibit a more aggressive course and adopt atypical clinical patterns such as optic nerve involvement. Herein we report an atypical case of optic neuritis secondary to syphilis in an HIV negative patient. This case highlights the importance of considering syphilis in the differential diagnosis of ocular inflammation and of obtaining HIV serology, since both diseases share common risk factors. PMID- 26868531 TI - Neoadjuvant chemotherapy of triplet regimens of docetaxel/cisplatin/5-FU (DCF NAC) may improve patient prognosis of cStage II/III esophageal squamous cell carcinoma-propensity score analysis. AB - BACKGROUND: Neoadjuvant chemotherapy (NAC) with CF (cisplatin/5-FU) was demonstrated to improve survival of clinical stage II/III (cStage II/III) esophageal squamous cell carcinoma (ESCC), however prognostic outcome remains unsatisfactory. We have recently reported preliminary potentiality of short-term survival benefit by NAC with DCF (docetaxel/cisplatin/5-FU). PATIENTS AND METHODS: Thirty-eight ESCC patients who underwent DCF NAC between 2009 and 2012 were investigated for prognosis with a median follow-up period of 49 months as compared to those with CF NAC. RESULTS: (1) ESCC patients with DCF NAC showed 66% of 3-year progression-free survival (PFS), which is significantly superior to that of CF NAC (38%) (p = 0.018). ESCC patients with DCF NAC showed 79% of 3-year overall survival (OS), which is marginally significantly superior to that of CF NAC (65%) (p = 0.093). (2) The multivariate Cox proportional hazards model revealed that DCF NAC was an independent prognostic factor for PFS (p = 0.0013) and OS (p = 0.047), respectively, when adjusted for patient sex, age, cT, cN, and preoperative borderline resectability. (3) Patients with more advanced stage were rather frequently included in DCF NAC than in CF NAC, however there was no significant difference. Nevertheless, propensity score (PS) to predict DCF NAC was significantly higher than CF NAC (p = 0.019). (4) Both NAC and PS were again applied to the multivariate Cox proportional hazards model, and DCF NAC was the only remnant prognostic indicator for PFS (p = 0.0044) and OS (p = 0.063). CONCLUSION: Prognosis may be significantly improved in cStage II/III ESCC patients who underwent DCF NAC than those with CF NAC. PMID- 26868533 TI - [Leber-Coats' disease: A retrospective study of 10 patients]. AB - INTRODUCTION: Retrospective study analyzing clinical characteristics and treatment of children affected by Leber-Coats' disease. METHOD: Children with Leber-Coats' disease seen in Edouard-Herriot Hospital, Lyon, between January 2004 and September 2013 were included. The following clinical characteristics were reported: sex, age at diagnosis, presenting symptom, Shields' stage, treatment used, and visual outcomes. RESULTS: Ten children were included in our study. Mean age at diagnosis was 5.5 years. The disease was unilateral in 9/10 cases. The presenting symptom was loss of vision in 7/10 cases, strabismus in 3/10 cases, and microphthalmos in 1 case. The diagnosis was made fortuitously during a follow up of familial congenital cataract in 2 patients. No cases of leukocoria were seen. Shields' stages were distributed as follows: stage 1, 2A and 2B: 1 case each, stage 3A1: 7 cases, stage>3A1: no cases. Laser photocoagulation was used up to stage 2B, combined with cryotherapy in stage 3A. Stage 1 and 2A were associated with relatively good final visual acuity. Significant macular lipid exudate (stage>2A) was associated with a worse prognosis. CONCLUSION: These epidemiological data help us to better characterize these patients' prognosis. Early diagnosis seems to improve visual outcomes. PMID- 26868534 TI - [Eye and cat scratch disease: A case series]. AB - INTRODUCTION: Cat scratch disease is a pleiomorphic condition, sometimes with isolated ophthalmic involvement. We report the clinical observations of seven cases with ophthalmologic manifestations of cat scratch disease. OBSERVATIONS: There were seven patients, with a median age of 52 years, of whom five were women and three had unilateral involvement. Six exhibited Leber's stellate neuroretinitis, an incomplete syndrome in two cases, and one associated with chorioretinal foci. One patient had isolated retinal infiltrates. The diagnosis of cat scratch disease was confirmed by Bartonella henselae serology, positive in all cases. All patients received treatment with doxycycline. Ocular complications (with optic atrophy and macular retinal pigment epithelial changes) were noted in five cases. DISCUSSION: Ocular bartonellosis is an atypical clinical form. It requires a directed ancillary work-up with serology or PCR, which has the peculiarity of being highly specific if not very sensitive. Treatment is above all preventive. Antibiotics may be initiated. CONCLUSION: Cat scratch disease must be excluded in the work-up of posterior uveitis. PMID- 26868535 TI - [Genotype-phenotype correlation in ten Tunisian families with non-syndromic retinitis pigmentosa]. AB - PURPOSE: To evaluate the clinical phenotype of ten Tunisian families with non syndromic retinitis pigmentosa (RP), to characterize genes and mutations causing these conditions, and to elaborate phenotype-genotype correlations. METHODS: Descriptive clinical genetic study of 114 individuals, of whom 27 are affected by non-syndromic RP. Ophthalmic examination and various visual tests were performed. DNA was analyzed using single nucleotide polymorphism, microsatellite genotyping and direct sequencing to determine the genes and mutations involved. RESULTS: We identified seven mutated genes: RPE65, RDH12, USHER 2A, PDE6a, PDE6b, CRB1, and NR2E3. Analysis of phenotype-genotype correlation indicated that some genes were associated with specific phenotypes. In RPE65 mutations, we found early onset dystrophy, nystagmus, keratoconus, white dot deposits in earlier stages and clumped pigment in later stages. The RDH12-associated phenotype (juvenile RP) showed severe and early-onset dystrophy, diffuse spicule pigmentation, macular edema and thickening, and tomographic re-organization of retinal layers. The CRB1 mutation was characterized by preserved para-arteriolar retinal pigment epithelium and no hemeralopia. CONCLUSION: RP is clinically and genetically heterogeneous. The two ultimate goals of research are to provide efficient clinical diagnostic of affected gene by phenotype-genotype correlation and to design novel treatment regimens. Our goal is to create a specific chip for our population, and then future research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina and the development of gene therapy approaches. PMID- 26868536 TI - Epidemiological survey of ossification of the posterior longitudinal ligament by using clinical investigation registration forms. AB - BACKGROUND: In Japan, ossification of the posterior longitudinal ligament (OPLL) has been designated as an intractable disease by the Ministry of Health, Labour, and Welfare. Here we aimed to clarify the epidemiological characteristics of severe OPLL patients by analyzing a national registry of this disease that uses clinical investigation registration forms. METHODS: We retrospectively investigated clinical investigation registration forms for 24,502 patients with OPLL. We examined the sex distribution, age of disease onset, period from disease onset to registration, family history, site of ossification as determined by plain radiographs, Japanese Orthopaedic Association score, and number of OPLL surgeries. RESULTS: The male-to-female ratios were 2.7:1 and 1.9:1 for new and renewed registrations, respectively. The mean ages at disease onset were 61.1 and 59.7 years for new and renewed registrations, respectively. The mean periods from disease onset to registration were 2.6 and 8.4 years for new and renewed registrations, respectively. The percentages of new registrations with and without family history were 5.3% and 51.5%, respectively (unknown for 43.3%). Of the new registrations, 3511, 359, and 200 cases exhibited ossification in the cervical spine, thoracic spine, and lumbar spine, respectively; the corresponding numbers for renewed registrations were 13,710, 2484, and 1508. The Japanese Orthopaedic Association score was 9.9 +/- 3.6 for new registrations, and the mean score recovery rate for renewed registrations was 6.0%. The number of OPLL surgeries was one or zero, two, three, four, or five for 21,785, 2167, 412, 99, and 39 patients, respectively, with 11.1% of all patients having undergone multiple surgeries. CONCLUSIONS: This study offers new insight into the epidemiological characteristics of severe OPLL. In particular, we found that the age of disease onset was higher than previously reported, the period from disease onset to registration (surgery) was relatively short, and about 90% of the patients required only a single surgery. PMID- 26868538 TI - The respective roles of polar/nonpolar binary patterns and amino acid composition in protein regular secondary structures explored exhaustively using hydrophobic cluster analysis. AB - Several studies have highlighted the leading role of the sequence periodicity of polar and nonpolar amino acids (binary patterns) in the formation of regular secondary structures (RSS). However, these were based on the analysis of only a few simple cases, with no direct mean to correlate binary patterns with the limits of RSS. Here, HCA-derived hydrophobic clusters (HC) which are conditioned binary patterns whose positions fit well those of RSS, were considered. All the HC types, defined by unique binary patterns, which were commonly observed in three-dimensional (3D) structures of globular domains, were analyzed. The 180 HC types with preferences for either alpha-helices or beta-strands distinctly contain basic binary units typical of these RSS. Therefore a general trend supporting the "binary pattern preference" assumption was observed. HC for which observed RSS are in disagreement with their expected behavior (discordant HC) were also examined. They were separated in HC types with moderate preferences for RSS, having "weak" binary patterns and versatile RSS and HC types with high preferences for RSS, having "strong" binary patterns and then displaying nonpolar amino acids at the protein surface. It was shown that in both cases, discordant HC could be distinguished from concordant ones by well-differentiated amino acid compositions. The obtained results could, thus, help to complement the currently available methods for the accurate prediction of secondary structures in proteins from the only information of a single amino acid sequence. This can be especially useful for characterizing orphan sequences and for assisting protein engineering and design. PMID- 26868537 TI - LPS causes pericyte loss and microvascular dysfunction via disruption of Sirt3/angiopoietins/Tie-2 and HIF-2alpha/Notch3 pathways. AB - Recent studies reveal a crucial role of pericyte loss in sepsis-associated microvascular dysfunction. Sirtuin 3 (SIRT3) mediates histone protein post translational modification related to aging and ischemic disease. This study investigated the involvement of SIRT3 in LPS-induced pericyte loss and microvascular dysfunction. Mice were exposed to LPS, expression of Sirt3, HIF 2alpha, Notch3 and angiopoietins/Tie-2, pericyte/endothelial (EC) coverage and vascular permeability were assessed. Mice treated with LPS significantly reduced the expression of SIRT3, HIF-2alpha and Notch3 in the lung. Furthermore, exposure to LPS increased Ang-2 while inhibited Ang-1/Tie-2 expression with a reduced pericyte/EC coverage. Intriguingly, knockout of Sirt3 upregulated Ang-2, but downregulated Tie-2 and HIF-2alpha/Notch3 expression which resulted in a dramatic reduction of pericyte/EC coverage and exacerbation of LPS-induced vascular leakage. Conversely, overexpression of Sirt3 reduced Ang-2 expression and increased Ang-1/Tie-2 and HIF-2alpha/Notch3 expression in the LPS treated mice. Overexpression of Sirt3 further prevented LPS-induced pericyte loss and vascular leakage. This was accompanied by a significant reduction of the mortality rate. Specific knockout of prolyl hydroxylase-2 (PHD2) increased HIF-2alpha/Notch3 expression, improved pericyte/EC coverage and reduced the mortality rate in the LPS-treated mice. Our study demonstrates the importance of SIRT3 in preserving vascular integrity by targeting pericytes in the setting of LPS-induced sepsis. PMID- 26868539 TI - Objective but not subjective sleep predicts memory in community-dwelling older adults. AB - Research on the relationship between habitual sleep patterns and memory performance in older adults is limited. No previous study has used objective and subjective memory measures in a large, older-aged sample to examine the association between sleep and various domains of memory. The aim of this study was to examine the association between objective and subjective measures of sleep with memory performance in older adults, controlling for the effects of potential confounds. One-hundred and seventy-three community-dwelling older adults aged 65 89 years in Victoria, Australia completed the study. Objective sleep quality and length were ascertained using the Actiwatch 2 Mini-Mitter, while subjective sleep was measured using the Pittsburgh Sleep Quality Index. Memory was indexed by tests of retrospective memory (Hopkins Verbal Learning Test - Revised), working memory (n-back, 2-back accuracy) and prospective memory (a habitual button pressing task). Compared with normative data, overall performance on retrospective memory function was within the average range. Hierarchical regression was used to determine whether objective or subjective measures of sleep predicted memory performances after controlling for demographics, health and mood. After controlling for confounds, actigraphic sleep indices (greater wake after sleep onset, longer sleep-onset latency and longer total sleep time) predicted poorer retrospective (?R(2) = 0.05, P = 0.016) and working memory (?R(2) = 0.05, P = 0.047). In contrast, subjective sleep indices did not significantly predict memory performances. In community-based older adults, objectively-measured, habitual sleep indices predict poorer memory performances. It will be important to follow the sample longitudinally to determine trajectories of change over time. PMID- 26868540 TI - Elimination of polycyclic aromatic hydrocarbons from smoked sausages by migration into polyethylene packaging. AB - The objective of this work was a study of interactions between a smoked meat product and plastic packaging to find a possibility of elimination of polycyclic aromatic hydrocarbons (PAH) from smoked sausages by migration into the packaging. Smoked meat sausages were packed into o-polyamide/low density polyethylene laminated film and content of four PAH was determined at 0, 15, 30, 45, 60, 75, 90, 120, 150 and 180 min by HPLC. During this time, total PAH4 content decreased from 30.1 to 5.7 MUg/kg, benzo[a]anthracene decreased from 11.5 to 2.1 MUg/kg, chrysene from 9.4 to 1.9 MUg/kg, benzo[b]fluoranthene from 5.3 to 0.6 MUg/kg and benzo[a]pyrene from 3.9 to 1.1 MUg/kg while PAH4 content in non-packed sausages remained at a constant level. So, while sausages did not meet European safety limits set for PAH4 content of 12 MUg/kg and 2 MUg/kg for benzo[a]pyrene before packaging, these limits were met at the end of the experiment. This decrease was brought about by migration of PAH4 from sausages into low density polyethylene packaging bulk and the measure of decrease can be predicted by a kinetic equation, making it possible to calculate PAH content equal to any time of experiment as well as the time of interaction necessary to fulfil EU legislative limits. PMID- 26868541 TI - A novel thyroglobulin-binding lectin from the brown alga Hizikia fusiformis and its antioxidant activities. AB - A lectin (HFL) was isolated from the brown alga, Hizikia fusiformis, through ion exchange on cellulose DE52 and HPLC with a TSK-gel G4000PWXL column. SDS-PAGE showed that HFL had a molecular mass of 16.1 kDa. The HPLC (with a TSK-gel G4000PWXL column) indicated that HFL is a tetramer in its native state. The total carbohydrate content was 41%. Glucose, galactose and fucose were the monosaccharide units of HFL, and the normalized mol% values were 6, 14 and 80, respectively. HFL contains a large amount of the acidic amino acid, Asx. The beta elimination reaction suggested that the oligosaccharide and peptide moieties of HFL may belong to the N-glucosidic linkage. The amino acid sequences, of about five segments of HFL, were acquired by MALDI-TOF/TOF, and the sequences have no homology with other lectins. HFL was found to agglutinate sheep erythrocytes. The hemagglutination activity was inhibited by thyroglobulin, from bovine thyroid, but not by any of the monosaccharides tested. The lectin reaction was independent of the presence of the divalent cation Ca(2+). HFL showed free radical scavenging activity against hydroxyl, DPPH and ABTS(+) radicals. PMID- 26868542 TI - Enhancement of colour stability of anthocyanins in model beverages by gum arabic addition. AB - This study investigated the potential of gum arabic to improve the stability of anthocyanins that are used in commercial beverages as natural colourants. The degradation of purple carrot anthocyanin in model beverage systems (pH 3.0) containing L-ascorbic acid proceeded with a first-order reaction rate during storage (40 degrees C for 5 days in light). The addition of gum arabic (0.05 5.0%) significantly enhanced the colour stability of anthocyanin, with the most stable systems observed at intermediate levels (1.5%). A further increase in concentration (>1.5%) reduced its efficacy due to a change in the conformation of the gum arabic molecules that hindered their exposure to the anthocyanins. Fluorescence quenching measurements showed that the anthocyanin could have interacted with the glycoprotein fractions of the gum arabic through hydrogen bonding, resulting in enhanced stability. Overall, this study provides valuable information about enhancing the stability of anthocyanins in beverage systems using natural ingredients. PMID- 26868544 TI - Effect of cream fermentation on microbiological, physicochemical and rheological properties of L. helveticus-butter. AB - The primary objective of this study was to evaluate the physicochemical and rheological properties of butter produced by Lactobacillus helveticus fermented cream. The incorporation of putative probiotic - the L. helveticus, to ferment cream prior to butter production was anticipated to alter the nutritional composition of butter. Changes in crude macronutrients and the resultant modification relating to textural properties of butter induced upon metabolic activities of L. helveticus in cream were focused in this research. Fermented butter (LH-butter) was produced by churning the cream that was fermented by lactobacilli at 37 degrees C for 24 h. Physicochemical analysis, proximate analysis and rheology properties of LH-butter were compared with butter produced using unfermented cream (control). LH-butter showed a significantly (P<0.05) higher fat content and acid value; lower moisture and ash; and was softer than the control. Cream fermentation modified nutritional and textural properties of butter in which LH-butter contained higher health beneficial unsaturated fatty acids than the control and thus rendered the product softer. Its enrichment with probiotics could thus further enhance its functional property. PMID- 26868543 TI - Sphingoid esters from the molecular distillation of squid oil: A preliminary bioactivity determination. AB - A mixture of sphingoid esters was isolated (1.4% w/w) from the molecular distillation of crude squid visceral oil. A preliminary investigation on the bioactivity profile and toxic potential of this residue was carried out by in vitro experiments. No cytotoxicity and a moderate lipase inhibition activity were highlighted. PMID- 26868546 TI - Effects of some cations on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) in a model system. AB - The present study aimed to investigate in detail the changes to 2-amino-1-methyl 6-phenylimidazo[4,5-b]pyridine (PhIP) and its precursors in the presence of some cations (i.e., K(+), Na(+), Ca(2+), Mg(2+), Fe(2+) and Fe(3+)) in a creatinine/phenylacetaldehyde model system. Results showed that PhIP yields decreased when Fe(2+)and Fe(3+) were added to a mixture of phenylacetaldehyde and creatinine. This decrease may be attributed to the fact that Fe(3+) can form complexes with various properties with creatinine and accelerate creatinine degradation. This pathway can disturb the reaction with phenylacetaldehyde, influence aldol condensation product formation, and suppress PhIP formation. Furthermore, Ca(2+)and Mg(2+) enhanced PhIP content. Such enhancement may be attributed to the fact that CaCl2 and MgCl2 promote aldol and aldol condensation product reactions with ammonia and formaldehyde. A possible mechanism for the action of cations during PhIP formation in a model system is also proposed. PMID- 26868545 TI - Pectin content and composition from different food waste streams. AB - In the present paper, 26 food waste streams were selected according to their exploitation potential and investigated in terms of pectin content. The isolated pectin, subdivided into calcium bound and alkaline extractable pectin, was fully characterized in terms of uronic acid and other sugar composition, methylation and acetylation degree. It was shown that many waste streams can be a valuable source of pectin, but also that pectin structures present a huge structural diversity, resulting in a broad range of pectin structures. These can have different physicochemical and biological properties, which are useful in a wide range of applications. Even if the data could not cover all the possible batch by batch and country variabilities, to date this represents the most complete pectin characterization from food waste streams ever reported in the literature with a homogeneous methodology. PMID- 26868547 TI - Comparative evaluation of methods for the detection of 2-alkylcyclobutanones as indicators for irradiation treatment of cashew nuts and nutmeg. AB - Irradiation of food products and ingredients must be indicated by proper labeling. This study evaluated the appropriateness of the European Standard EN 1785:2003 for the detection of 2-alkylcyclobutanones, which are radiolysis products of fatty acids, in cashew nuts and nutmeg and confirmed its suitability to detect irradiation of cashew nut samples at average absorbed doses of 1 kGy and above. An alternative method was developed, which is based on matrix solid phase dispersion and subsequent separation and detection of oxime derivatives of 2-alkylcyclobutanones by high performance-high resolution mass spectrometry. It is more rapid, less resource consuming, and more sensitive than EN 1785:2003. This method allowed detection of 2-alkylcyclobutanones in cashew nuts irradiated at 100 Gray and in nutmeg irradiated at 400 Gray. None of the 26 cashew nut and 14 nutmeg samples purchased in different EU Member States contained traces of 2 alkylcyclobutanones. PMID- 26868548 TI - Influence of storage conditions in the evolution of phytochemicals in nutraceutical products applying high resolution mass spectrometry. AB - An adequate knowledge about possible transformation of bioactive compounds in nutraceutical products during long storage is important in order to know potential modifications of this type of compounds. In this study, one year monitoring was performed in different types of nutraceutical products based on natural extracts (green tea, soy, royal jelly and grapes) observing the appearance of new bioactive compounds, which were not detected at the initial conditions, as well as the decrease of some of the detected compounds. To determine these transformation products, an analytical procedure based on high resolution mass spectrometry (Exactive-Orbitrap analyzer) was applied. It was noted that transformation products were detected after 3 months of storage in green tea and soy products, while 6 months were necessary to observe transformation products in royal jelly. PMID- 26868549 TI - Carotenoid profiling from 27 types of paprika (Capsicum annuum L.) with different colors, shapes, and cultivation methods. AB - In this study, we investigated carotenoid profiles and contents from 27 types of paprika with different colors (red, orange, and yellow), shapes (blocky and conical), and cultivation methods (soil and soilless). We simultaneously analyzed 12 kinds of carotenoids using UPLC equipped with an HSS T3 column for 30 min, and we identified six kinds of carotenoids in red paprika and nine types in orange and yellow paprika. Zeaxanthin concentrations in orange paprika were in the range of 85.06+/-23.37-151.39+/-5.94 mg/100 g dry weight (dw), which shows that orange paprika is a great source of zeaxanthin. Generally, red paprika is a great source of capsanthin. However, a new cultivar, 'Mini Goggal Red', contained large amounts of zeaxanthin (121.41+/-30.10 mg/100 g dw) even though its visible color is red. This is very meaningful considering that consumers have a preference for red color and the potent functional value of zeaxanthin. Carotenoid profiles and concentrations in blocky and conical type paprika were not significantly different in red paprika except the 'Mini Goggal Red' cultivar and yellow paprika. Blocky type orange paprika contains plenty of zeaxanthin, unlike conical type orange paprika. Three new cultivars of the conical type were cultivated in both soil culture and soilless culture in the same province, and carotenoid profiles and concentrations were similar, showing that both cultivations methods can be used. PMID- 26868550 TI - Determination of ractopamine in pork using a magnetic molecularly imprinted polymer as adsorbent followed by HPLC. AB - A new magnetic molecularly imprinted polymers (MMIPs) for separation and concentration of ractopamine (RAC) were prepared using surface molecular imprinting technique with methacryloyl chloride as functional monomer and RAC as template. The MMIPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and vibrating sample magnetometer. The results of re-binding experiments indicated that the MMIPs had fast adsorption kinetics and could reach binding equilibrium within 20 min, and the adsorption capacity of the MMIPs was 2.87-fold higher than that of the corresponding non-imprinted polymer. The selectivity of the MMIPs was evaluated according to its recognition to RAC and its analogues. The synthesized MMIPs were successfully applied to extraction, followed by high performance liquid chromatography to determine RAC in real food samples. Spiked recoveries ranged from 73.60% to 94.5%, with relative standard deviations of <11.17%. PMID- 26868551 TI - Effect of cooking methods on nutritional quality and volatile compounds of Chinese chestnut (Castanea mollissima Blume). AB - This study aimed to evaluate the effects of different cooking methods on the content of important nutrients and volatiles in the fruit of Chinese chestnut. The nutritional compounds, including starch, water-soluble protein, free amino acids, reducing sugar, sucrose, organic acids and total flavonoids, of boiled, roasted and fried chestnuts were significantly (P<0.05) lower than those of fresh chestnuts after cooking, while the amylose, fat, crude protein and total polyphenol content varied slightly (P>0.05). L-Aspartic acid, L-glutamic acid and L-arginine were found to be the main reduced free amino acids in cooked chestnuts. The main aromatic compositions in fresh chestnuts were aldehydes and esters, while ketones, furfural and furan were formed in cooked chestnuts due to the Maillard reaction and degradation of saccharides, amino acids and lipids. Principle component analysis demonstrated that roasting and frying had a similar effect on the nutritional composition of chestnuts, which differed from that of the boiling process. PMID- 26868552 TI - Dual effects of slightly acidic electrolyzed water (SAEW) treatment on the accumulation of gamma-aminobutyric acid (GABA) and rutin in germinated buckwheat. AB - In the present study, the dual effects of slightly acidic electrolyzed water (SAEW) treatment on gamma-aminobutyric acid (GABA) and rutin accumulation of germinated buckwheat were evaluated during germination. The results showed that SAEW treatment (pH 5.83, ACC of 20.3 mg/L) could promote the accumulation of GABA and rutin in germinated buckwheat. The GABA and rutin contents of SAEW-germinated buckwheat reached 143.20 and 739.9 mg/100 g respectively, which is significantly higher than those of control (P<0.05). Moreover, SAEW treatment could increase the activity of glutamic acid decarboxylase (GAD) and phenylalanine ammonialyase (PAL) and thus result in the GABA and rutin accumulation of germinated buckwheat. The results suggested that SAEW treatment could promote the rutin accumulation of germinated buckwheat by influencing phenylpropanoid secondary metabolic pathway instead of the inhibition of rutin degrading enzyme (RDE) activity. In addition, SAEW treatment had no adverse impact on the sprouts growth and could reduce the microbial populations of germinated buckwheat during germination. PMID- 26868553 TI - Microencapsulation of sulforaphane from broccoli seed extracts by gelatin/gum arabic and gelatin/pectin complexes. AB - Sulforaphane is a phytochemical that has received attention in recent years due to its chemopreventive properties. However, the uses and applications of this compound are very limited, because is an unstable molecule that is degraded mainly by changes in temperature and pH. In this research, the use of food grade polymers for microencapsulation of sulforaphane was studied by a complex coacervation method using the interaction of oppositely charged polymers as gelatin/gum arabic and gelatin/pectin. The polymers used were previously characterized in moisture content, ash and nitrogen. The encapsulation yield was over 80%. The gelatin/pectin complex had highest encapsulation efficiency with 17.91%. The presence of sulforaphane in the complexes was confirmed by FTIR and UV/visible spectroscopy. The materials used in this work could be a new and attractive option for the protection of sulforaphane. PMID- 26868554 TI - Improvement of the nutraceutical quality of broccoli sprouts by elicitation. AB - Epidemiological studies show an inverse association between Brassica consumption and chronic diseases. Phytochemicals are thought to be beneficial for human health and therefore responsible for this protective effect. Increasing their levels into Brassica food is considered an expedient nutritional strategy that can be achieved through the manipulation of growth conditions by elicitors. In this work we systematically evaluated the influence of treatment with different elicitors (sucrose, mannitol, NaCl, 1-aminocyclopropane-L-carboxylic acid, salicylic acid and methyl jasmonate) on the phytochemical composition of broccoli sprouts. The content of total and single glucosinolates, total phenolic compounds, total flavonoids, total anthocyanins, vitamin C and E and beta carotene was assessed. The exposure to different elicitors produced concentration and elicitor-dependent specific changes in the content of all the phytochemicals considered. Sucrose, identified as the most effective elicitor by principal component analysis, induced a significant increase of total and specific glucosinolates, vitamin C, total anthocyanins and polyphenols. Sucrose is likely to represent an effective tool to increase the nutritional value of broccoli sprouts. PMID- 26868555 TI - Development and applicability of a ready-to-use PCR system for GMO screening. AB - With the growing number of GMOs introduced to the market, testing laboratories have seen their workload increase significantly. Ready-to-use multi-target PCR based detection systems, such as pre-spotted plates (PSP), reduce analysis time while increasing capacity. This paper describes the development and applicability to GMO testing of a screening strategy involving a PSP and its associated web based Decision Support System. The screening PSP was developed to detect all GMOs authorized in the EU in one single PCR experiment, through the combination of 16 validated assays. The screening strategy was successfully challenged in a wide inter-laboratory study on real-life food/feed samples. The positive outcome of this study could result in the adoption of a PSP screening strategy across the EU; a step that would increase harmonization and quality of GMO testing in the EU. Furthermore, this system could represent a model for other official control areas where high-throughput DNA-based detection systems are needed. PMID- 26868556 TI - Stability and metabolism of Arbutus unedo bioactive compounds (phenolics and antioxidants) under in vitro digestion and colonic fermentation. AB - The natural antioxidants of Arbutus unedo highlight the importance of this fruit as natural source of bioactive compounds. In the present study, to evaluate the stability of phenolic compounds, ascorbic acid and fat-soluble antioxidants (alpha-tocopherol, beta-carotene and lutein), in vitro gastrointestinal digestion was applied to A. unedo fruit. After that, the non-absorbable fraction was anaerobically incubated with human faeces and the metabolic pathway for gallotannins, ellagitannins, flavan-3-ols and anthocyanins from A. unedo fruit was proposed. The results showed that the presence of pectin from the fruit hampered the solubilization of the phenolic compounds (with exception of gallic and ellagic acids) and fat-soluble vitamins during gastric digestion. Degradation of pectin-gel during the duodenal digestion favored the release of the phenolic compounds and fat-soluble antioxidants to the media. The catabolic activity of human microbiota led to the generation of a wide range of simple phenols, such as p-hydroxybenzoic acid and catechol, derived from the catabolism of gallotannins, ellagitannins, flavan-3-ols and anthocyanins. PMID- 26868557 TI - Effects of different stunning methods on the flesh quality of grass carp (Ctenopharyngodon idellus) fillets stored at 4 degrees C. AB - The effects of stunning methods (percussion (T1), stunning at -22 degrees C in a freezer (T2), and immersion in ice slurry (T3)) on the flesh quality of grass carp fillets were evaluated in terms of K-value, total volatile base nitrogen (TVB-N), electrical conductivity (EC), total viable counts (TVC), biogenic amines, and sensory scores during storage. Moreover, fillets were analyzed periodically for pH, hardness, acid phosphatase activity, and the content of glycogen, adenosine triphosphate (ATP), and lactate. Significantly slower ATP depletion, slower reduction in pH, slower lactate formation, and higher initial glycogen level were observed in T3 compared to T1 and T2 (P<0.05). Grass carp stunned by percussion showed higher TVB-N, EC, TVC, total biogenic amines, and lower sensory scores. Significantly lower TVC (P<0.05) was exhibited in T3, which indicated that stunning in ice slurry could improve the quality and prolong the shelf life of grass carp. PMID- 26868558 TI - Simultaneous quantification of sulforaphene and sulforaphane by reverse phase HPLC and their content in Raphanus sativus L. var. caudatus Alef extracts. AB - A simple, rapid and precise HPLC assay was developed for the well-known anti cancer isothiocyanates-sulforaphene (SE) and sulforaphane (SF). The analytical system comprised RP-C18 column with isocratic 5% THF-95% water. High resolution was obtained (and eluted) of two distinct HPLC peaks of similar structures SE and SF analytes (at 23.01+/-0.02 and 25.65+/-0.03 min, respectively). The respective LOD vs. LOQ for SE and SF was 0.34 and 0.36 MUg/ml vs. 1.02 and 1.08 MUg/ml. This assay had the best linearity and accuracy. The recoveries were in the range of 96.83-101.17%. SF and SE were quantified in the pod of Raphanus sativus L. var. caudatus Alef extracts (2253.05+/-246.18 and 111.94+/-16.49 MUg/g in the crude extract, respectively), while only SE was detected in the stem (1105.14+/-243.10 MUg/g crude extract), as SF was lower than the detection limit. The validated method thus minimized and expedited simultaneous SE and SF analysis. PMID- 26868559 TI - Antioxidant dietary fibre recovery from Brazilian Pinot noir grape pomace. AB - Brazilian grape pomace was extracted in hot water, and a factorial experiment was used to evaluate polysaccharide recovery. The dependent variables were the temperature, particle size and solute:solvent ratio. Polysaccharide yields varied from 3% to 10%, and the highest sugar content was observed when extraction was carried out at 100 degrees C from finely sized particles (?249 MUm) in a 1:12 solute:solvent ratio. The monosaccharide composition of extracts obtained from flours were, on average, Rha:Ara:Xyl:Man:Gal:Glc:GalA in a 3:32:2:13:11:20:19 M ratio, with varying Glc:GalA ratios. (13)C NMR and HSQC spectra confirmed the presence of pectic- and glucose-based polysaccharides in the extracts. Phenolic compounds were found after pomace extraction, and catechin, gallic acid and epicatechin were the principal compounds identified. The extracts also had ABTS radical scavenging capacity (from 8.00 to 46.60 mMol Trolox/100 g pomace). These findings indicate that these grape pomace flours are rich in antioxidant dietary fibre and have a potential use as food ingredients. PMID- 26868560 TI - Contributing effect of various washing procedures and additives on the decline pattern of diethofencarb in crown daisy, a model of leafy vegetables. AB - The effects of various washing procedures, including stagnant, running, and stagnant and running tap water, and the use of washing solutions and additives, namely NaCl (1% and 2%), vinegar (2%, 5%, and 10%), detergent (0.5% and 1%), and charcoal (1% and 2%), on the reduction rate of diethofencarb were estimated in field-incurred crown daisy, a model of leafy vegetables, grown under greenhouses located in 3 different areas (Gwangju, Naju, and Muan). The original Quick, Easy, Cheap, Effective, Rugged, and Safe "QuEChERS" method was modified for extraction and liquid chromatography-tandem mass spectrometry (LC/MS/MS) was used for analysis. The recovery of diethofencarb in unwashed and washed samples was satisfactory and ranged between 84.28% and 115.32% with relative standard deviations (RSDs) of <6%. The residual levels decreased following washing with stagnant, running, and stagnant+running tap water (i.e., decline in levels increased from 65.08% to 85.02%, 69.99 to 86.79, and 74.75 to 88.96, respectively). The percentage of decline increased and ranged from 77.46% to 91.19% following washing with various solutions. Application of 1% detergent was found to be the most effective washing method for reducing the residues in crown daisy. Additionally, washing with stagnant and running tap water or even stagnant water for 5 min might reduce the residue levels substantially, making the prepared food safe for human consumption. PMID- 26868561 TI - Reducing retrogradation and lipid oxidation of normal and glutinous rice flours by adding mango peel powder. AB - Green and ripe mango peel powders (MPP) were added to normal rice flour (NRF) and glutinous rice flour (GRF) at three levels (400, 800 and 1200 ppm) and their effects on physicochemical properties and lipid oxidation inhibition were investigated. Overall, MPP increased the breakdown viscosity and reduced the final viscosity in rice flours when compared to the control. Decreasing in retrogradation was observed in both NRF and GRF with MPP added of all levels. MPP addition also significantly inhibited the lipid oxidation of all flours during storage (30 days). Retrogradation values were strongly negatively correlated with total phenolic and flavonoid contents, but not with fiber content. The hydrogen bonds and hydrophilic interactions between phenolic compounds with amylopectin molecule may be involved the decrease of starch retrogradation, especially GRF. We suggest that the addition of MPP not only reduced the retrogradation but also inhibited the lipid oxidation of rice flour. PMID- 26868563 TI - Pacific whiting frozen fillets as affected by postharvest processing and storage conditions. AB - Whole fish and H&G (headed and gutted) fish were stored under refrigeration (<4 degrees C) for 0, 2, and 5 days and subsequently filleted and frozen at -18 degrees C and -80 degrees C. Frozen fillets were analyzed during 24 weeks of storage. The activity of trimethylamine-N-oxide demethylase (TMAOase) decreased more quickly at -18 degrees C than -80 degrees C. TMAOase reduction was distinctively noted at -18 degrees C storage. Formaldehyde (FA) induced by TMAOase increased at all treatments at -18 degrees C as frozen storage extended to 24 weeks, but it was near zero at -80 degrees C up to 12 weeks of storage. Textural toughening, low water retention ability, and low salt soluble protein resulted from the denaturation function of FA. A sudden decrease in surface hydrophobicity at 24 weeks, when stored at -18 degrees C, resulted from FA induced unfolding and subsequent aggregation. FA concentration appeared to affect protein aggregations and textual toughening of fillets during frozen storage. PMID- 26868562 TI - Long-term storage effect on chemical composition, nutritional value and quality of Greek onion landrace "Vatikiotiko". AB - The effect of storage at two temperatures (5+/-1 and 25+/-1 degrees C and 60 70+/-5% RH for both temperatures) on marketability and quality features of dry bulbs of local landrace "Vatikiotiko", "Sivan F1", "Red Cross F1" and "Creamgold" was examined. During storage measurements for fresh and dry weight of bulbs, tunic and flesh color, bulb firmness, nutritional value and mineral composition were taken at regular intervals. Storage concluded when either bulbs lost marketable quality or sprouting occurred. "Vatikiotiko" onion can be stored for at least 7months at 25+/-1 degrees C, whereas at 5+/-1 degrees C storage could be prolonged without significant marketability and quality loss. The fact that "Vatikiotiko" landrace can be considered a "storage" onion has to be capitalized in order to increase total production and yield, since storage could cover the market needs that arise throughout the year. PMID- 26868564 TI - Identification of natural lactoylcholine in lactic acid bacteria-fermented food. AB - Acetylcholine (AcCh) is a major neurotransmitter and an agonist of nicotinic and muscarinic receptors in non-neuronal systems. Artificially synthesized lactoylcholine (LaCh) has potent nicotinic activity equal to that of AcCh. In this study, we report the isolation and purification of natural AcCh and LaCh from a lactic-fermented food known to reduce blood pressure. To our knowledge, we are the first to isolate natural LaCh. The choline esters were isolated using a novel purification procedure combining a weak cation-exchange cartridge with ODS and pentafluorophenyl HPLC columns, and the structure of LaCh was identified via various analyses. Assessment of D- and L-LaCh showed that the isolated LaCh was an enantiomer mixture with a D/L ratio of 1.6. D-LaCh induced vasorelaxation of thoracic aortas from spontaneously hypertensive rats (EC50=3.83*10(-7) M), while L-LaCh did not. Our results suggest that choline esters could be new functional ingredients in lactic-fermented foods. PMID- 26868565 TI - Microfabricated interdigitated Au electrode for voltammetric determination of lead and cadmium in Chinese mitten crab (Eriocheir sinensis). AB - An in-situ plating bismuth modified interdigitated Au electrode (IAE) was developed for determination of Pb(2+) and Cd(2+) in crab. The IAE was fabricated and used as counter electrode and working electrode. Cyclic voltammetry (CV) was performed with the IAE for studying electrochemical performance, showing clear redox peaks. The key operational parameters were optimized, which were 600 MUg L( 1) of Bi(3+) concentration, 0.1 mol L(-1) of acetate buffer (pH 4.5), -1.2V of deposition potential and 180 s of deposition time. Under optimized condition, the linear range of IAE was from 5 to 50 MUg L(-1) for both metal ions, with detection limit (threefold signal-to-noise) of 0.74 MUg L(-1) for Pb(2+) and 0.86 MUg L(-1) for Cd(2+). Finally, the developed sensor was applied to detect Pb(2+) and Cd(2+) in crab extract solutions by standard addition method. The results were in good agreement with outcomes obtained by inductively coupled plasma mass spectrometry. PMID- 26868566 TI - Effect of magnesium salt concentration in water-in-oil emulsions on the physical properties and microstructure of tofu. AB - The aim of this research was to prepare water-in-oil (W/O) emulsions encapsulating different concentrations of magnesium chloride (MgCl2) and to investigate the effect of W/O emulsions on the physical properties and microstructure of tofu. The results showed that the stability of W/O emulsions improved as the concentrations of polyglycerol polyricinoleate (PGPR) and MgCl2 increased. Dynamic viscoelastic measurements indicated that gelation time decreased with increasing MgCl2 concentration in W/O emulsions, suggesting a more rapid reaction between magnesium ions and protein molecules. As the concentration of MgCl2 in W/O emulsions increased, the yield and water content of tofu decreased, while the protein and crude fat contents and hardness values increased. At a concentration of 2.0M MgCl2 in W/O emulsion, the WHC and microstructure of the tofu samples were optimal. The variations in the physical properties of tofu were attributed to the concentration of magnesium ions and the coagulation rate. PMID- 26868567 TI - Fortification of dark chocolate with spray dried black mulberry (Morus nigra) waste extract encapsulated in chitosan-coated liposomes and bioaccessability studies. AB - Fine-disperse anionic liposomes containing black mulberry (Morus nigra) extract (BME) were prepared by high pressure homogenization at 25,000 psi. Primary liposomes were coated with cationic chitosan (0.4, w/v%) using the layer-by-layer depositing method and mixed with maltodextrin (MD) (20, w/v%) prior to spray drying. After that, spray dried liposomal powders containing BME were added to chocolates with alkalization degrees (pH 4.5, 6, 7.5) at conching temperatures of 40 degrees C, 60 degrees C, and 80 degrees C. The results showed that, compared to spray dried extract, chitosan coated liposomal powders provided better protection of anthocyanin content in both increased temperature and pH. In addition, encapsulation in liposomes enhanced in vitro bioaccessability of anthocyanins. Chocolate was fortified with encapsulated anthocyanins maximum 76.8% depending on conching temperature and pH. PMID- 26868568 TI - Improvement of grape and wine phenolic content by foliar application to grapevine of three different elicitors: Methyl jasmonate, chitosan, and yeast extract. AB - Phenolic compounds play a key role in grape and wine organoleptic properties, being therefore a key parameter in wine quality. Elicitor application constitutes an interesting field of research since it is indirectly involved in the accumulation of phenolic compounds. The aim of this study was to compare the effect of the application of three different elicitors on both grape and wine phenolic content. Methyl jasmonate, chitosan, and a commercial yeast extract were applied to the canopy at veraison and one week later. Results showed that foliar treatments carried out with methyl jasmonate and yeast extract achieved the best results, increasing grape and wine anthocyanin content when compared to the control. Moreover, the application of the yeast elicitor also enhanced grape stilbene content. In contrast, the chitosan treatment did not have a substantial impact on the phenolic compounds. The results of this study indicate that methyl jasmonate and yeast extract applications could be a simple practice to increase grape and wine phenolic content. PMID- 26868569 TI - Measurement of haem and total iron in fish, shrimp and prawn using ICP-MS: Implications for dietary iron intake calculations. AB - Twenty-five species of fish, shrimp and prawn from local markets in Bangladesh were analysed for concentrations of total Fe, haem Fe and non-haem Fe by ICP-MS. Total Fe and non-haem Fe concentrations were measured in nitric acid-digested samples and haem Fe was extracted using acidified 80% acetone for 60 min. Total Fe concentrations ranged from 0.55-14.43 mg/100 g FW, and haem Fe% ranged from 18%-93% of total Fe. Repeat extractions with 80% acetone recovered additional haem Fe, suggesting that previous measurement by this technique may have underestimated haem Fe content. Calculation of Fe balance (summing Fe in acetone extracts and Fe in the residue after haem Fe extraction) was not significantly different from total Fe, indicating the two processes recovered the different forms of Fe with similar effectiveness. PMID- 26868570 TI - Heat-pretreatment and enzymolysis behavior of the lotus seed protein. AB - Lotus seed protein (LSP) was heat-pretreated before enzymolysis in order to seek a greater degree of hydrolysis (DH) during enzymatic hydrolysis. The parameters including substrate concentration, temperature, pH, and papain concentration were optimized by response surface methodology in the enzymolysis of the heat pretreated LSP. The influence of substrate concentration on the non-pretreated LSP enzymolysis was assessed, and the enzymolysis was found to obey the Haldane model with inhibition by LSP substrate. The initial concentration of non pretreated LSP was inferred theoretically to be 11.07 g/L in order to avoid substrate inhibition. On the other hand, Chrastil model was fitted and the diffusion resistance constant values were in the range of 0.5-0.6 for the diffusion-controlled encounter of enzyme and substrate, implying that diffusion was a rate-limiting step. The heat-pretreatment at 60 degrees C for 60 min could increase the DH of the LSP, which enhanced the efficiency of the enzymolysis by papain. PMID- 26868571 TI - Oxidative stability and antioxidant enzyme activities of dry-cured bacons as affected by the partial substitution of NaCl with KCl. AB - This study investigated the influence of partial substitution of NaCl with KCl on protein and lipid oxidation as well as antioxidant enzyme activities in dry-cured bacons during processing. The partial substitution was 0% KCl (I), 40% KCl (II), and 70% KCl (III). Compared with 0% KCl (I), the substitution of 40% NaCl with KCl did not significantly influence the protein and lipid oxidation and antioxidant enzyme activities. The bacons that were treated with 70% KCl treatment (III) showed increased lipid oxidation and antioxidant enzyme GSH-Px activity, whereas samples treated with formulas I and II showed higher protein oxidation and antioxidant enzyme catalase activity. These results demonstrate that the substitution of NaCl with KCl by more than 40% may significantly affect protein and lipid oxidation and that for the substitution of NaCl in further processed meat products with other chloride salts, salt content is very important for control of protein and lipid biochemical changes in finished products. PMID- 26868572 TI - Study of total dry matter and protein extraction from canola meal as affected by the pH, salt addition and use of zeta-potential/turbidimetry analysis to optimize the extraction conditions. AB - Total dry matter and proteins were differentially and preferentially extracted from canola meal (CM) under different conditions. The effect of the extraction medium pH, CM concentration and salt concentrations were found to have different influences on the extractability of total dry matter and proteins from CM. The pH of the extracting medium had the most significant effect. The maximal total dry matter (42.8+/-1.18%) extractability was obtained with 5% CM at pH 12 without salt addition, whereas the maximal for total protein (58.12+/-1.47%) was obtained with 15% CM under the same conditions. The minimal extractability for the dry matter (26.63+/-0.67%) was obtained with 5% CM at pH 10 without salt added and the minimal protein extractability was observed in a 10% CM at pH 10, in 0.01 NaCl. Turbidity and zeta-potential measurements indicated that pH 5 was the optimum condition for the highest protein extraction yield. SDS-PAGE analysis showed that salt addition contributes to higher solubility of canola proteins specifically cruciferin fraction, although it reduces napin extraction. PMID- 26868573 TI - Effects of divalent cations on the formation of 4(5)-methylimidazole in fructose/ammonium hydroxide caramel model reaction. AB - The objective of the present study was to detail the changes of 4(5) methylimidazole (4-MI) and its precursors in the presence of divalent cations (Ca(2+), Mg(2+)) in a fructose/ammonium hydroxide caramel model system. The content of 4-MI and its precursor methylglyoxal (MGO) was inhibited by divalent cations (Ca(2+), Mg(2+)). The possible explanation might be that fructose and its Heyns product glucosamine interact with divalent cations to form complexes and inhibit the degradation of glucosamine into MGO. Moreover, the changes of fructose, NH4(+) and brown intensity in the presence of divalent cations indicated that fructose and glucosamine underwent intra-intermolecular polymerisation into melanoidins rather than the degradation reaction into aldehydes and ketones. PMID- 26868574 TI - Antioxidant activities from different rosemary clonal lines. AB - Rosemary extract is widely used in food industry and carnosic acid is reported to be the major component that is responsible for its antioxidant activities. However, it is unclear how the numerous plant metabolites interact and contribute to the overall antioxidant activity. In this study, with poultry fat as the model food system, rosemary extract from six clonal lines were evaluated that each represented a different genetic variant. As expected, rosemary extract with higher carnosic acid content had higher antioxidant activity. However, rosemary extract which had carnosic acid removed retained a significant amount of activity. Furthermore, when the individual contributions of carnosic acid and the portion without carnosic acid were evaluated separately, neither was shown to be responsible for the overall level of its stabilization effect from rosemary extract as a whole entity. The interactions among different plant metabolites have a major impact on the overall antioxidant capabilities of rosemary extract. PMID- 26868575 TI - Pesticide contamination of Tenebrio molitor (Coleoptera: Tenebrionidae) for human consumption. AB - The use of pesticides contributes to the productivity and the quality of the cultivated crop. A large portion of the agricultural produce is not consumed as it is not an edible part or the quality of the product is too low. This waste of agricultural produce can be valorised as a substrate for the production of certain insects for human consumption. However, pesticides applied on the plants might accumulate during the life cycle of the insects fed on the waste materials and may cause a health risk to humans consuming the insects. Pesticide residues in larvae of the yellow mealworm, Tenebrio molitor, were investigated. We monitored the accumulation of pesticides in the larvae upon consumption of contaminated fresh produce. An increased uptake rate by the insects was found for pesticides with higher Kow-values. Excretion of pesticides by the insect was inversely related to the log(Kow) values of the pesticides. PMID- 26868576 TI - Detecting ethanol and acetaldehyde by simple and ultrasensitive fluorimetric methods in compound foods. AB - There is a need for simple, accurate, and rapid analysis of ethanol (Eth) and acetaldehyde (AA) in a wide variety of beverages and foods. A novel enzymatic assay coupled to formation of fluorescent chromophore is presented. Eth detection was further improved by adding semicarbazide to the reaction mixture, which interacts with AA and prevents its inhibitory effect on Eth oxidation. The limits of detection of Eth (0.5 mg/L) and AA (0.9 mg/L) are comparable with the performance of modern gas chromatography techniques. The repeatability of Eth and AA detection in various foods (9% on average) was lower than that with commercial kits (23%). The high sensitivity of the developed method enables detection of AA in common foods [e.g., bio-yogurt (12.2 mg/L), and the existence of endogenous Eth (1.8 mg/L) and AA (2.0 mg/L) in bacteria-free non-fermented bovine milk], which could not measured so far by enzymatic methods. PMID- 26868577 TI - Polymerization of wheat gluten and the changes of glutenin macropolymer (GMP) during the production of Chinese steamed bread. AB - Polymerization of gluten and the changes of glutenin macropolymer (GMP) during the production of Chinese steamed bread (CSB) were investigated, providing a theoretical basis to improve and regulate the quality of CSB. Protein extractability and free sulfhydryl (SH) contents increased to some degree during the dough preparation stage, but significantly (P<0.05) decreased during steaming. Remarkable protein aggregates were observed in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) patterns. The microstructure study of the gas cell and the protein network by confocal laser scanning microscopy (CLSM) further revealed the formation of a continuous and three-dimensional gluten network. The loss and recovery of GMP wet weight during dough processing were significant (P<0.05). Glutenin depolymerization negatively correlated with GMP wet weight and the contents of high molecular weight glutenin subunits (HMW GS) and low molecular weight glutenin subunits (LMW-GS). Gluten polymerization led to a decrease in G' and G" of GMP while gluten depolymerization induced a slight recovery in G' and G" of GMP. PMID- 26868578 TI - Comparative study of muscle proteins in relation to the development of yake in three tropical tuna species yellowfin (Thunnus albacares), big eye (Thunnus obesus) and skipjack (Katsuwonus pelamis). AB - Burnt tuna (BT), or yake-niku, is a quality flaw of the muscle characterised by a pale colour and grainy and exudative texture. Cathepsin-L, water soluble and total protein components from normal and BT muscles, from three tropical tuna species - yellowfin (YFT, Thunnus albacares), bigeye (BET, Thunnus obesus) and skipjack (SKJ, Katsuwonus pelamis) - were compared by electrophoretic and western blot analyses to identify biomarkers for BT. As expected, SDS-PAGE patterns were species-specific but differences, due to BT, were observed only between some low ionic strength extracts of BET and YFT. Protein oxidation and cell proliferation analysed by immunoblotting did not show differences between BT and normal muscles. Gelatine zymography revealed different gelatinase activity patterns that, although not linked to BT, may affect the final texture of the muscle. A 43 kDa band, identified as creatine kinase by proteomic analysis, showed the potential to be a good indicator for BT in BET and YFT. PMID- 26868579 TI - Production of rosmarinic acid and salvianolic acid B from callus culture of Salvia miltiorrhiza with cytotoxicity towards acute lymphoblastic leukemia cells. AB - Salvia miltiorrhiza (SM) Bunge is one of the widely-used Chinese medicinal herbs. In this study, the chemical constituents and anticancer potential of SM stems and leaves were examined with those of respective callus cultures. The callus culture for stem and leaf explants was initiated in modified Murashige and Skoog (MS) medium. Active constituents of respective extracts were analyzed by high performance liquid chromatography coupled with DAD and MS (HPLC-DAD-MS). Rosmarinic acid (RA) and salvianolic acid B (Sal B) were determined to be the main phenolic compounds. Quantitative analyses revealed that callus stem extracts produced higher amount of RA and Sal B (stem RA: 1.27+/-0.38%; stem Sal B: 0.87+/ 0.20%) than callus leaf did (leaf RA: 0.28+/-0.02%; leaf Sal B: 0.07+/-0.03%). Stem and leaf callus extracts exerted cytotoxic effects towards CCRF-CEM cells (stem: 13.1+/-0.90 MUg/ml; leaf: 18.1+/-0.33 MUg/ml). As expected, stem extract with higher amount of RA and Sal B showed lower IC50 value than leaf extract. These findings suggest the possibility to isolate bioactive constituents with anticancer properties from in vitro callus cultures of stems and leaves of SM. PMID- 26868580 TI - Antioxidative free and bound phenolic constituents in botanical fractions of Indian specialty maize (Zea mays L.) genotypes. AB - Specialty maize genotypes viz. QPM (quality protein maize), Baby corn, Popcorn and Sweet corn, which are usually consumed in whole forms can be good supplements of phenolic antioxidants. Botanical fractions of these maize genotypes were analyzed to explore the distribution of free and bound phenolics. HPLC and ESI MS/MS results indicated the presence of vanillic, syringic, p-hydroxybenzoic, caffeic, p-coumaric, ferulic and isoferulic acids along with cyanidin-3-O glucoside, kaempferol and quercetin. Germs of maize samples contained significantly higher free phenolics than pericarps, whereas, pericarps contained 74-83% of bound ones. QPM and Popcorn contained only 3% free phenolics whereas, Baby corn and Sweet corn had 14-17%. Unlike in peroxide scavenging and reducing capacity, anti-radical capacity of free phenolics of germs was significantly higher than that of pericarps. Free phenolics contributed 0.2-1.65%, 2-5% and 42 49% in anti-radical, peroxide scavenging and reducing capacity, respectively. Among lipophilic tocochromanols gamma-tocopherol was the most abundant isomer in the samples among which Sweet corn contained the most (84.2 MUg/g). Data showed that specialty maize genotypes are rich sources of hydrophilic and lipophilic bioactives and are natural antioxidants. PMID- 26868581 TI - Phenolic composition, ascorbic acid content, and antioxidant capacity of Spanish jujube (Ziziphus jujube Mill.) fruits. AB - The interest in Ziziphus jujube is growing because it is an excellent source of nutrients and phytochemicals, and can contribute to a healthy diet. Nutritional compounds (phenolic compounds and L-ascorbic acid), and antioxidant capacity of 4 Spanish jujube cultivars were studied. Polyphenols were identified by LC-MS-QTof and quantified by UPLC-PDA-FL. A total of 25 polyphenolic compounds were identified and classified as 10 flavan-3-ols, 13 flavonols, 1 flavanone, and 1 dihydrochalcone. The content of total polyphenols (TP) ranged from 1442 to 3432 mg/100 g dry matter (dm) in fruits of the cultivars 'DAT' and 'PSI', respectively. Flavan-3-ols, the major group of polyphenols in jujube represented ~92% of the TP content, whereas flavonols only amounted for about ~8% each. The content of L-ascorbic acid was very high and took values in the range of 387-555 mg/100 g fresh weight (fw). Some Spanish jujube cultivars, especially 'PSI' and 'MSI', may be selected to promote the growth of cultivars with valuable nutritional and phytochemical beneficial effects on human health. PMID- 26868583 TI - Novel arginine deiminase-based method to assay L-arginine in beverages. AB - A highly selective and sensitive enzymatic method for the quantitative determination of L-arginine (Arg) has been developed. The method is based on the use of recombinant bacterial arginine deiminase (ADI) isolated from the cells of a recombinant strain Escherichia coli and o-phthalaldehyde (OPA) as a chemical reagent. Ammonia, the product of the enzymatic digestion of Arg by ADI, reacts with OPA and forms in the presence of sulfite a product, which can be detected by spectrophotometry (S) and fluorometry (F). The linear concentration range for Arg assay in the final reaction mixture varies for ADI-OPA-F variant of the method from 0.35 MUM to 24 MUM with the detection limit of 0.25 MUM. For ADI-OPA-S variant of the assay, the linearity varies from 0.7 MUM to 50 MUM with the detection limit of 0.55 MUM. The new method was tested on real samples of wines and juices. A high correlation (R=0.978) was shown for the results obtained with the proposed and the reference enzymatic method. PMID- 26868582 TI - Heated apple juice supplemented with onion has greatly improved nutritional quality and browning index. AB - Although fruit juices are very popular, enzymatic browning occurs easily. Browning of fruit juice deteriorates nutrition value and product quality due to oxidation of polyphenol compounds. Therefore, development of natural food additives that reduce browning will be beneficial for improving quality of fruit juices. Onion has been reported to be a potent natural anti-browning agent. Here, we compared unheated and heated apple juices pre-supplemented with onion with respect to browning and nutritional quality. The unheated apple juice supplemented with onion showed reduced browning as well as increased total soluble solid, total phenol concentration, radical scavenging activities, and ferric reducing and copper chelating activities without any change in flavonoid concentration. On the other hand, heated juice supplemented with onion not only showed improved values for these parameters but also markedly increased flavonoid concentration. Thus, we conclude that application of heating and onion addition together may greatly improve quality of apple juice. PMID- 26868584 TI - Quality changes and predictive models of radial basis function neural networks for brined common carp (Cyprinus carpio) fillets during frozen storage. AB - To investigate and predict quality of 2% brined common carp (Cyprinus carpio) fillets during frozen storage, free fatty acids (FFA), salt extractable protein (SEP), total sulfhydryl (SH) content, and Ca(2+)-ATPase activity were determined at 261 K, 253 K, and 245 K, respectively. There was a dramatic increase (P<0.05) in FFA and a sharp decrease (P<0.05) in SH at 261 K during the first 3 weeks. SEP decreased to 67.31% after 17 weeks at 245 K, whereas it took about 7 weeks and 13 weeks to decrease to the same extent at 261 K and 253 K, respectively. Ca(2+) ATPase activity kept decreasing to 18.28% after 7 weeks at 261 K. Furthermore, radial basis function neural networks (RBFNNs) were developed to predict quality (FFA, SEP, SH, and Ca(2+)-ATPase activity) of brined carp fillets during frozen storage with relative errors all within +/-5%. Thus, RBFNN is a promising method to predict quality of carp fillets during storage at 245-261 K. PMID- 26868585 TI - Effect of curing salts and probiotic cultures on the evolution of flavor compounds in dry-fermented sausages during ripening. AB - The effect of the concentration of curing salts, the nature of the probiotic culture (free or immobilized Lactobacillus casei ATCC 393 on wheat grains) and the ripening time on the generation of volatile compounds in probiotic dry fermented sausages was investigated. Samples were collected after 1, 28 and 71 days of ripening and subjected to SPME GC/MS analysis. All factors affected significantly the concentration of all volatile compounds. Noticeably, the content of esters, organic acids and total volatiles was significantly increased after 28 and 71 days of ripening in almost all products. In most cases, reduction of curing salts content resulted in significant increase of esters and organic acids during ripening, whereas the opposite effect was observed in carbonyl compounds at days 28 and 71. Principal Component Analysis of the semi quantitative data revealed that primarily the ripening process affected the volatile composition. PMID- 26868586 TI - Bog bilberry phenolics, antioxidant capacity and nutrient profile. AB - Phenolics and nutrient profiles of bog bilberry (Vaccinium uliginosum L.) collected from high mountain pastures in northeast Anatolia (Turkey) were examined for the first time in this study. The major soluble sugar identified in the berry was fructose, following by glucose, and the main organic acid identified was citric acid, followed by malic acid. Eleven phenolic acids and 17 anthocyanin 3-glycosides were identified and quantified. Caffeic acid in the free and glycoside forms and syringic acid in the ester form were the major phenolic acids, and the major individual anthocyanin present in the berry was malvidin 3 glucoside (24%). The highest total phenolics and anthocyanin contents were obtained from the anthocyanin fraction in conjunction with the highest antioxidant capacity, followed by the polyphenolic and aqueous fractions, FRAP, ORAC and DPPH, in that order. Our findings can be used to compare bog bilberry with other Vaccinium berries and to help clarify the relative potential health benefits of different berries. PMID- 26868587 TI - Phytochemical distribution in hull and cotyledon of adzuki bean (Vigna angularis L.) and mung bean (Vigna radiate L.), and their contribution to antioxidant, anti inflammatory and anti-diabetic activities. AB - Total saponin content, total phenolics content, total flavonoids content, condensed tannin content in hull, cotyledon and whole grain of both adzuki bean and mung bean were determined by colorimetric methods. Vitexin and isovitexin contents in mung bean were determined by HPLC. Antioxidant effects were evaluated with DPPH scavenging activity and ferric reducing antioxidant power assay. In vitro anti-inflammatory and anti-diabetic effects of beans were evaluated by protease and aldose reductase inhibitory assays, respectively. The results indicated that the bean hulls were the most abundant in phytochemicals and largely contributed antioxidant activities, anti-inflammatory effects and anti diabetic effects of whole grains. The result showed that mung bean hull was the most abundant with vitexin at 37.43 mg/g and isovitexin at 47.18 mg/g, respectively. Most of the phytochemicals and bioactivities were most predominantly contributed by the bean hulls with exception for condensed tannin of mung bean; which was more abundant in the cotyledon than its hull. PMID- 26868589 TI - Diurnal-activity Patterns of the Small Bee-eater (Merops orientalis) in Southern India. AB - The diurnal time-activity patterns of the Small Bee-eater (Merops orientalis) were studied between 2005 and 2006 in the Nagapattinam District of Southern India. Bee-eaters were observed to spend an average of 52.5% of their day time scanning, 21.3% feeding, 13.3% flying, 8.8% resting and 4.1% engaging in preening activities. The time spent on scanning varied among seasons in 2005 (p<0.05) and among time blocks (p<0.05), but it did not vary among years or habitats (p>0.05). The feeding patterns differed among years, seasons within years, time blocks and habitats (p<0.05). The flying habits varied among years, time blocks and habitats (p<0.05) but did not change between seasons within years (p>0.05). The resting habits differed among years and habitats (p<0.05) but did not differ among seasons within years or time blocks (p>0.05). Preening differed among years and time blocks (p<0.05) but did not vary among seasons within years or habitats (p>0.05). We conclude that several factors, such as food availability, environmental factors and predation threats, may affect the diurnal activity patterns of Bee-eaters between habitats and seasons; a further study could clarify this conclusion. PMID- 26868588 TI - 18F-FDG PET-CT performed before and during radiation therapy of head and neck squamous cell carcinoma: Are they independent or complementary to each other? AB - INTRODUCTION: The aims of this study are to evaluate the prognostic value of metabolic parameters derived from (18) F-FDG PET-CT performed before definitive radiation therapy (RT) (prePET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to assess the additive prognostic values of FDG PET-CT performed during RT (iPET). METHODS: One hundred patients with MPHNSCC treated with radical RT underwent staging prePET and iPET performed during the third week of treatment. The maximum standardized uptake value (SUVmax ), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary tumour were analysed for both prePET and iPET, and results were correlated with loco-regional recurrence-free survival (LRFS), disease-free survival (DFS), metastatic failure-free survival (MFFS) and overall survival (OS), using Kaplan Meier analysis. Optimal cut-offs (OC) for prePET and iPET were derived from Receiver Operating Characteristic curves. Patients with metabolic parameters above/below the individual OC of prePET as well as iPET (i.e. combined prePET and iPET (comPET)) were evaluated against their outcomes. RESULTS: Median age was 61 years (range 39-81), median follow-up of 20 months (range 4-70, mean 27), and AJCC 7th Edition clinical stage II, III and IV were 8, 24 and 68 patients respectively. Metabolic values below individual OC in comPET were found to be associated with statistically significant improvements (P < 0.05) in DFS, LRFS and OS. In addition, patients with SUVmax above the OC in comPET were associated with worse MFFS (P = 0.011) and confirmed on both univariate (P = 0.019) and multivariate analyses (P = 0.04). CONCLUSION: Addition of iPET significantly improves the prognostic values of all three metabolic parameters and can potentially be used in future adaptive local and systemic therapy trials. PMID- 26868591 TI - A Description of Lecithocladium angustiovum (Digenea: Hemiuridae) in Short Mackerel, Rastrelliger brachysoma (Scombridae), of Indonesia. AB - Lecithocladium angustiovum is identified from the stomach (87.33%) and the intestine (12.67%) of Indonesian short mackerel (Rastrelliger brachysoma). The description includes an elongated body; a mean total length of 1018.84 um; and an ecsoma of 47.52% of the total length. The oral and ventral sucker ratio is 1:0.63, and the pharynx length is 97.42 um. The sequence results were obtained by 18s rDNA gene sequencing of the 354 basepair (bp) DNA segment, and the mean base composition (%) was 17.7 A; 35.7 T; 29.6 G; and 17.1 C. A phylogenetic tree was constructed to demonstrate the genetic distance between L. angustiovum and sequences from Lecithocladium excisum, Dinurus longisinus, Plerurus digitatus and Lecithochirium caesionis obtained from GenBank. PMID- 26868590 TI - A Comparison of Culture Characteristics between Human Amniotic Mesenchymal Stem Cells and Dental Stem Cells. AB - In the past decade, the field of stem cell biology is of major interest among researchers due to its broad therapeutic potential. Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Stem cells can be classified into two main types: adult stem cells (adult tissues) and embryonic stem cells (embryos formed during the blastocyst phase of embryological development). This review will discuss two types of adult mesenchymal stem cells, dental stem cells and amniotic stem cells, with respect to their differentiation lineages, passage numbers and animal model studies. Amniotic stem cells have a greater number of differentiation lineages than dental stem cells. On the contrary, dental stem cells showed the highest number of passages compared to amniotic stem cells. For tissue regeneration based on animal studies, amniotic stem cells showed the shortest time to regenerate in comparison with dental stem cells. PMID- 26868592 TI - Isolation and Characterisation of Endophytic Nitrogen Fixing Bacteria in Sugarcane. AB - Endophytic nitrogen fixing bacteria were isolated from the leaves, stems and roots of industrial variety (cv. U-Thong 3; UT3), wild and chewing sugarcane plants grown for 6 weeks in nitrogen (N)-free sand. Eighty nine isolates of endophytic bacteria were obtained on N-free agar. An acetylene reduction assay (ARA) detected nitrogenase activity in all 89 isolates. Three isolates from the chewing (C2HL2, C7HL1 and C34MR1) sugarcane and one isolate from the industrial sugarcane (UT3R1) varieties were characterised, and their responses to different yeast extract concentrations were investigated. Three different responses in nitrogenase activity were observed. Isolates C2HL2 and C7HL1 exhibited major increases with the addition of 0.005% yeast extract, C34MR1 exhibited no response, and UT3R1 exhibited a significant decrease in nitrogenase activity with 0.005% yeast extract. In all the isolates, nitrogenase activity decreased with further increase of the yeast extract to 0.05%. The highest nitrogenase activity was observed in isolates C2HL2 and C7HL1, which had 16S rRNA gene sequences that were closely related to Novosphingobium sediminicola and Ochrobactrum intermedium, respectively. PMID- 26868593 TI - Morphological and Molecular Identification of Holothuria (Merthensiothuria) leucospilota and Stichopus horrens from Pangkor Island, Malaysia. AB - This preliminary study aimed to identify a commercial gamat species, Stichopus horrens Selenka, 1867, and a timun laut species, Holothuria (Mertensiothuria) leucospilota (Brandt, 1835), from Pangkor Island, Perak, Malaysia, employing morphological techniques based on the shape of the ossicles and molecular techniques based on the cytochrome c oxidase I (COI) mitochondrial DNA (mtDNA) gene. In Malaysia, a gamat is defined as a sea cucumber species of the family Stichopodidae with medicinal value, and timun laut refers to non-gamat species. S. horrens is very popular on Pangkor Island as a main ingredient in the traditional production of air gamat and minyak gamat, while H. leucospilota is the most abundant species in Malaysia. In contrast to previous studies, internal body parts (the respiratory tree and gastrointestine) were examined in this study to obtain better inferences based on morphology. The results showed that there were no ossicles present in the gastrointestine of H. leucospilota, and this characteristic is suggested as a unique diagnostic marker for the timun laut species. In addition, the presence of Y-shaped rods in the respiratory tree of S. horrens subsequently supported the potential to use internal body parts to identify the gamat species. Phylogenetic analysis of the COI mtDNA gene of the sea cucumber specimens using the neighbour-joining method and maximum likelihood methods further confirmed the species status of H. leucospilota and S. horrens from Pangkor Island, Perak, Malaysia. The COI mtDNA gene sequences were registered with GenBank, National Center for Biotechnology Information (NCBI), US National Library of Medicine (GenBank accession no.: KC405565-KC405568). Although additional specimens from various localities will be required to produce more conclusive results, the current findings provide better insight into the importance of complementary approaches involving morphological and molecular techniques in the identification of the two Malaysian sea cucumber species. PMID- 26868594 TI - Influence of External Nitrogen on Nitrogenase Enzyme Activity and Auxin Production in Herbaspirillum seropedicae (Z78). AB - The production of nitrogenase enzyme and auxins by free living diazotrophs has the potential to influence the growth of host plants. In this study, diazotrophs were grown in the presence of various concentrations of nitogen (N) to determine the optimal concentration of N for microbial growth stimulation, promotion of gaseous N (N2) fixation, and phytohormone production. Therefore, we investigate whether different levels of N supplied to Herbaspirillum seropedicae (Z78) have significant effects on nitrogenase activity and auxin production. The highest nitrogenase activity and the lowest auxin production of H. seropedicae (Z78) were both recorded at 0 gL(-1) of NH4Cl. Higher levels of external N caused a significant decrease in the nitrogenase activity and an increased production of auxins. In a subsequent test, two different inoculum sizes of Z78 (10(6) and 10(12) cfu/ml) were used to study the effect of different percentages of acetylene on nitrogenase activity of the inoculum via the acetylene reduction assay (ARA). The results showed that the optimal amount of acetylene required for nitrogenase enzyme activity was 5% for the 10(6) cfu/ml inoculum, whereas the higher inoculum size (10(12) cfu/ml) required at least 10% of acetylene for optimal nitrogenase activity. These findings provide a clearer understanding of the effects of N levels on diazotrophic nitrogenase activity and auxin production, which are important factors influencing plant growth. PMID- 26868595 TI - Reduction of MTT to Purple Formazan by Vitamin E Isomers in the Absence of Cells. AB - The yellow tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) is widely used to determine cell viability in cell proliferation and cytotoxic assays. MTT is reduced by metabolically active cells to form an insoluble purple formazan product that is quantifiable by spectrophotometry. It is the most common and direct assay for cell viability. However, in this present study, we demonstrated that the vitamin E isomers alpha beta-gamma-delta-tocotrienols and alpha-tocopherol were able to reduce MTT into a formazan product, despite the absence of living cells. For comparison, a second method for determining cell viability, which is the neutral red uptake assay, was used in parallel with the MTT assay. The results showed that neutral red did not interact with the vitamin E isomers. Our findings suggest that the MTT assay is not suitable for studying the proliferative effects of vitamin E isomers on cell growth. PMID- 26868596 TI - Duplication and Diversification of Dipteran Argonaute Genes, and the Evolutionary Divergence of Piwi and Aubergine. AB - Genetic studies of Drosophila melanogaster have provided a paradigm for RNA interference (RNAi) in arthropods, in which the microRNA and antiviral pathways are each mediated by a single Argonaute (Ago1 and Ago2) and germline suppression of transposable elements is mediated by a trio of Piwi-subfamily Argonaute proteins (Ago3, Aub, and Piwi). Without a suitable evolutionary context, deviations from this can be interpreted as derived or idiosyncratic. Here we analyze the evolution of Argonaute genes across the genomes and transcriptomes of 86 Dipteran species, showing that variation in copy number can occur rapidly, and that there is constant flux in some RNAi mechanisms. The lability of the RNAi pathways is illustrated by the divergence of Aub and Piwi (182-156 Ma), independent origins of multiple Piwi-family genes in Aedes mosquitoes (less than 25Ma), and the recent duplications of Ago2 and Ago3 in the tsetse fly Glossina morsitans. In each case the tissue specificity of these genes has altered, suggesting functional divergence or innovation, and consistent with the action of dynamic selection pressures across the Argonaute gene family. We find there are large differences in evolutionary rates and gene turnover between pathways, and that paralogs of Ago2, Ago3, and Piwi/Aub show contrasting rates of evolution after duplication. This suggests that Argonautes undergo frequent evolutionary expansions that facilitate functional divergence. PMID- 26868597 TI - Gene Expression Variation Resolves Species and Individual Strains among Coral Associated Dinoflagellates within the Genus Symbiodinium. AB - Reef-building corals depend on symbiotic mutualisms with photosynthetic dinoflagellates in the genus Symbiodinium. This large microalgal group comprises many highly divergent lineages ("Clades A-I") and hundreds of undescribed species. Given their ecological importance, efforts have turned to genomic approaches to characterize the functional ecology of Symbiodinium. To date, investigators have only compared gene expression between representatives from separate clades-the equivalent of contrasting genera or families in other dinoflagellate groups-making it impossible to distinguish between clade-level and species-level functional differences. Here, we examined the transcriptomes of four species within one Symbiodinium clade (Clade B) at ~20,000 orthologous genes, as well as multiple isoclonal cell lines within species (i.e., cultured strains). These species span two major adaptive radiations within Clade B, each encompassing both host-specialized and ecologically cryptic taxa. Species specific expression differences were consistently enriched for photosynthesis related genes, likely reflecting selection pressures driving niche diversification. Transcriptional variation among strains involved fatty acid metabolism and biosynthesis pathways. Such differences among individuals are potentially a major source of physiological variation, contributing to the functional diversity of coral holobionts composed of unique host-symbiont genotype pairings. Our findings expand the genomic resources available for this important symbiont group and emphasize the power of comparative transcriptomics as a method for studying speciation processes and interindividual variation in nonmodel organisms. PMID- 26868599 TI - Localized self-heating in large arrays of 1D nanostructures. AB - One dimensional (1D) nanostructures offer a promising path towards highly efficient heating and temperature control in integrated microsystems. The so called self-heating effect can be used to modulate the response of solid state gas sensor devices. In this work, efficient self-heating was found to occur at random networks of nanostructured systems with similar power requirements to highly ordered systems (e.g. individual nanowires, where their thermal efficiency was attributed to the small dimensions of the objects). Infrared thermography and Raman spectroscopy were used to map the temperature profiles of films based on random arrangements of carbon nanofibers during self-heating. Both the techniques demonstrate consistently that heating concentrates in small regions, the here called "hot-spots". On correlating dynamic temperature mapping with electrical measurements, we also observed that these minute hot-spots rule the resistance values observed macroscopically. A physical model of a random network of 1D resistors helped us to explain this observation. The model shows that, for a given random arrangement of 1D nanowires, current spreading through the network ends up defining a set of spots that dominate both the electrical resistance and power dissipation. Such highly localized heating explains the high power savings observed in larger nanostructured systems. This understanding opens a path to design highly efficient self-heating systems, based on random or pseudo-random distributions of 1D nanostructures. PMID- 26868598 TI - Genome-Wide Analysis Indicates Lineage-Specific Gene Loss during Papilionoideae Evolution. AB - Gene loss is the driving force for changes in genome and morphology; however, this particular evolutionary event has been poorly investigated in leguminous plants. Legumes (Fabaceae) have some lineage-specific and diagnostic characteristics that are distinct from other angiosperms. To understand the potential role of gene loss in the evolution of legumes, we compared six genome sequenced legume species of Papilionoideae, the largest representative clade of Fabaceae, such as Glycine max, with 34 nonlegume plant species, such as Arabidopsis thaliana. The results showed that the putative orthologs of the 34 Arabidopsis genes belonging to 29 gene families were absent in these legume species but these were conserved in the sequenced nonlegume angiosperm lineages. Further evolutionary analyses indicated that the orthologs of these genes were almost completely lost in the Papillionoideae ancestors, thus designated as the legume lost genes (LLGs), and these underwent purifying selection in nonlegume plants. Most LLGs were functionally unknown. In Arabidopsis, two LLGs were well known genes that played a role in plant immunity such as HARMLESS TO OZONE LAYER 1 and HOPZ-ACTIVATED RESISTANCE 1, and 16 additional LLGs were predicted to participate in plant-pathogen interactions in in silico expression and protein protein interaction network analyses. Most of these LLGs' orthologs in various plants were also found to be associated with biotic stress response, indicating the conserved role of these genes in plant defense. The evolutionary implication of LLGs during the development of the ability of symbiotic nitrogen fixation involving plant and bacterial interactions, which is a well-known characteristic of most legumes, is also discussed. Our work sheds light on the evolutionary implication of gene loss events in Papilionoideae evolution, as well as provides new insights into crop design to improve nitrogen fixation capacity. PMID- 26868601 TI - The local density of optical states of a metasurface. AB - While metamaterials are often desirable for near-field functions, such as perfect lensing, or cloaking, they are often quantified by their response to plane waves from the far field. Here, we present a theoretical analysis of the local density of states near lattices of discrete magnetic scatterers, i.e., the response to near field excitation by a point source. Based on a pointdipole theory using Ewald summation and an array scanning method, we can swiftly and semi analytically evaluate the local density of states (LDOS) for magnetoelectric point sources in front of an infinite two-dimensional (2D) lattice composed of arbitrary magnetoelectric dipole scatterers. The method takes into account radiation damping as well as all retarded electrodynamic interactions in a self consistent manner. We show that a lattice of magnetic scatterers evidences characteristic Drexhage oscillations. However, the oscillations are phase shifted relative to the electrically scattering lattice consistent with the difference expected for reflection off homogeneous magnetic respectively electric mirrors. Furthermore, we identify in which source-surface separation regimes the metasurface may be treated as a homogeneous interface, and in which homogenization fails. A strong frequency and in-plane position dependence of the LDOS close to the lattice reveals coupling to guided modes supported by the lattice. PMID- 26868600 TI - Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health? AB - As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration. PMID- 26868602 TI - No Difference in Average Interdialytic Weight Gain Observed in a Randomized Trial With a Technology-Supported Behavioral Intervention to Reduce Dietary Sodium Intake in Adults Undergoing Maintenance Hemodialysis in the United States: Primary Outcomes of the BalanceWise Study. AB - OBJECTIVE: To evaluate the efficacy of behavioral counseling combined with technology-based self-monitoring for sodium restriction in hemodialysis (HD) patients. DESIGN: Randomized clinical trial. SUBJECTS: English literate adults undergoing outpatient, in-center intermittent HD for at least 3 months. INTERVENTIONS: Over a 16-week period, both the intervention and the attention control groups were shown 6 educational modules on the HD diet. The intervention group also received social cognitive theory-based behavioral counseling and monitored their diets daily using handheld computers. MAIN OUTCOME MEASURES: Average daily interdialytic weight gain (IDWGA) was calculated for every week of HD treatment over the observation period by subtracting the post-dialysis weight at the previous treatment time (t-1) from the pre-dialysis weight at the current treatment time (t), dividing by the number of days between treatments. Three 24 hour dietary recalls were obtained at baseline, 8 weeks, and 16 weeks and evaluated using the Nutrient Data System for Research. RESULTS: A total of 179 participants were randomized, and 160 (89.4%) completed final measurements. IDWGA did not differ significantly by treatment group at any time point considered (P > .79 for each). A significant differential change in dietary sodium intake observed at 8 weeks (-372 mg/day; P = .05) was not sustained at 16 weeks (-191 mg/day; P = .32). CONCLUSION: The BalanceWise Study intervention appeared to be feasible and acceptable to HD patients although IDWGA was unchanged and the desired behavioral changes observed at 8 weeks were not sustained. Unmeasured factors may have contributed to the mixed findings, and further research is needed to identify the appropriate patients for such interventions. PMID- 26868603 TI - Three-dimensional MDCT angiography for the assessment of arteriovenous grafts and fistulas in hemodialysis access. AB - Arteriovenous grafts and fistulas are placed for long-term hemodialysis access, and their associated complications can lead to considerable morbidity. Multi detector computed tomography (MDCT) images provide accurate delineation of hemodialysis access anatomy and show potential complications. This review makes the reader more familiar with vascular access anatomy and configurations, describes the appearance of access complications encountered on MDCT, and discusses endovascular and surgical treatment options for complications, which should aid in post-treatment evaluation. PMID- 26868605 TI - Sustained Infection Reduction in Outpatient Hemodialysis Centers Participating in a Collaborative Bloodstream Infection Prevention Effort. AB - Among dialysis facilities participating in a bloodstream infection (BSI) prevention collaborative, access-related BSI incidence rate improvements observed immediately following implementation of a bundle of BSI prevention interventions were sustained for up to 4 years. Overall, BSI incidence remained unchanged from baseline in the current analysis. Infect Control Hosp Epidemiol 2016;37:863-866. PMID- 26868604 TI - Preliminary Evaluation of Functional Swallow After Total Laryngectomy Using High Resolution Manometry. AB - INTRODUCTION: Understanding of swallowing pressures after total laryngectomy (TL) and what constitutes a "functional" swallow are limited. Mobile structures are altered or removed after TL, with consequent effects on pressure profiles. High resolution manometry (HRM) can characterize these pressures. METHODS: Six TL subjects without dysphagia and 6 controls underwent pharyngeal HRM. Timing and pressure variables for the velopharynx, mesopharynx, and upper esophageal sphincter (UES) were compared. Changes in variables due to bolus volume were evaluated in TL subjects. RESULTS: The TL subjects had increased duration of velopharyngeal pressure (P = .012). Maximum mesopharyngeal pressure was lower versus controls (P = .003). Maximal and total pre-opening (P = .002, P = .002) and post-closure (P = .001, P = .002) UES pressures were lower. Maximum mesopharyngeal pressure (P = .032) decreased with increasing bolus volume. CONCLUSIONS: Increased velopharyngeal pressure duration and total swallow duration reflect separation of the pharynx into distinct conduits for air and food, thus ensuring successful bolus passage without the need for respiration. Decreased UES pressure highlights the effects of disrupting the cricopharyngeal and rostral esophageal muscle fibers from their attachments to the larynx and performing a cricopharyngeal myotomy. Additional studies including subjects with dysphagia could further characterize the functional TL swallow and identify aspects susceptible to dysfunction. PMID- 26868606 TI - Declining mortality from adult pneumococcal infections linked to children's vaccination. AB - OBJECTIVE: To determine changes in mortality among adults with invasive pneumococcal disease (IPD) after introducing pneumococcal conjugate vaccines (PCVs) in children. METHODS: An active surveillance of adults with culture-proven IPD in Barcelona. Serotype-specific mortality and rates of disease and death were analysed in three periods: baseline (1994-2001), PCV7 (2002-2009) and PCV13 (2010 2013). RESULTS: Overall, IPD caused by PCV7 serotypes was associated with increased case fatality rate (24 percent). In patients 18-64 years (baseline vs. PCV7 vs. PCV13 periods), case fatality rate from IPD decreased (22 vs.14 vs. 12 percent), and it was associated with a decline in PCV7 serotypes (3.56 vs. 2.80 vs. 1.49 cases/10(5) person-years) and in PCV7 serotypes-specific death (0.74 vs. 0.53 vs. 0.09 deaths/10(5) person-years). In patients >=65 years, case fatality rate did not change (24 vs. 22 vs. 24 percent); however, there was a decline in PCV7 serotypes-specific death (4.94 vs. 3.58 vs. 2.45 deaths/10(5) person-years), and an increase in non-PCV serotypes-specific death (2.55 vs. 3.70 vs. 4.09 deaths/10(5) person-years). CONCLUSIONS: The use of PCVs for children was associated with a reduction of mortality from IPD in adults 18-64 years, through the indirect effect of herd protection. In older adults, age-related factors could play a role in IPD mortality. PMID- 26868607 TI - Induced Correspondence of a Local pi-Aromatic Sextet in Heteroannulenes: Synthesis and Characterization. AB - Acid-catalyzed [3+3] condensation reactions of two hitherto unknown tripyrrane moieties with pentafluorobenzaldehyde has led to the formation of new generation heteroannulene (4.1.4.1) and mutant heteroannulene (1.1.1.1.1.1). Inclusion of local pi-aromatic sextets, namely the N-methyl pyrrole rings through beta,beta linkages and alpha,beta-linkages, has led to the isolation of first ever heteroannulenes cross-conjugated at four points and two points respectively within the macrocycles. PMID- 26868608 TI - The Survivor's Paradox: Psychological Consequences of the Khmer Rouge Rhetoric of Extermination. AB - From 1975 to 1979 in Cambodia, during the four years of the Pol Pot regime, the rhetoric of extermination that perpetrators used to legitimize mass murder was a powerful instrument to deprive individuals of their humankind before killing them. Because every human community is founded on a metaphor claiming the inalterability of the social bond beyond the dead, the genocide project aims for its obliteration. By breaking the possible representation of a continuity and a social permanence between the dead and the living, the rhetoric of extermination claims, in a terrifying reality, that the only possible connection between the dead and the living concerns an identical physical condition: the living have already died or will pass away. This is the point where the rhetoric of extermination radically subverts one of the major symbolic aspects of the human condition. In the aftermath of extermination, the social existence of the deceased depends on the survivors' capacity to always carry them with them in a shared destiny. For those who survived, the consequences of this rhetoric may generate a distressful feeling of living in a world of death that conforms to the perpetrator's will. The survivor's paradox is undoubtedly one of the principal consequences of this will to deprive prisoners of their human condition. It is a kind of interiorization of the perpetrator's rhetoric. For the survivor to leave this world of death could mean abandoning the dead without a symbolic place where they could exist. But if he/she keeps them only in his/her own memory, that could signify that the survivor remains captive in the perpetrator's world of death. In both cases, the survivor's attempt to escape this paradox fails with the risk of confirming the abominable claim of the torturers. In this paper, the author emphasizes from an anthropological and psychotherapeutic point of view the dramatic logic of this rhetoric and its consequences long after the fact. PMID- 26868609 TI - Similarities between Human and Livestock Illnesses among the Luo in Western Kenya. AB - The objective of this study was to compare perceptions and practices in relation to human and livestock illness among the Luo in Western Kenya. Qualitative methods of data collection such as key informant interviews, open-ended, in-depth interviews, focus group discussions, narratives, and participant- and direct observations were applied. The study showed that there were significant parallels between human and livestock illnesses regarding terminology, perceptions of pathogenesis and treatment seeking practices. Even practitioners and their medications were often the same. The rationale behind pathogenesis in both cases was usually that illnesses resulted from some form of inhibition of flow through blockage or clogging of the various 'channels' in the body. Treatment aimed at decongesting or unblocking these channels so as to create openness that would guarantee normal flows and restore health. The study concludes that the domain of animal illness be taken more into account in human medical anthropological studies and vice versa. It further argues the case for considering these similarities when planning and implementing health care services. PMID- 26868610 TI - Health Seeking Behaviour of Mothers of Under-Five-Year-Old Children in the Slum Communities of Nairobi, Kenya. AB - Prompt and appropriate health seeking is critical in the management of childhood illnesses. This paper examines the health seeking behaviour in under-five child morbidity. It explores in detail actions taken by 28 mothers when their children become sick. Sixty-two in-depth interviews with mothers were conducted from four study communities. The mothers were identified from a demographic surveillance system. The interviews were tape-recorded, transcribed and thematically analysed. The study shows that mothers classify childhood illnesses into four main categories: (1) not serious-coughs, colds, diarrhoea; (2) serious but not life threatening-malaria; (3) sudden and serious-pneumonia; and (4) chronic and therefore not requiring immediate action-malnutrition, tuberculosis, chronic coughs. This classification is reflected in the actions taken and time it takes to act. Shops are used as the first source of healthcare, and when the care moves out of the home, private health facilities are used more compared to public health facilities, while even fewer mothers consult traditional healers. Consequently we conclude that there is a need to train mothers to recognize potentially life-threatening conditions and to seek appropriate treatment promptly. Drug vendors should be involved in intervention programs because they reach many mothers at the critical time of health seeking. PMID- 26868611 TI - Reconfiguring Relatedness in Anorexia. AB - Anthropological concepts of relatedness have not been addressed in any of the writings on anorexia, despite the literature being replete with negative connotations of sociality such as withdrawal, regression, and toxic families (in the form of 'obsessive mothers' or 'absent fathers'). As a departure to the vast literature on this topic, this multi-sited ethnographic project draws on the recent critiques and broadening of the concept of kinship to examine the ways in which a group of people with a diagnosis of anorexia understood and experienced relatedness in their everyday lives, that is, how they continually transformed connections by truncating, creating, sustaining and abandoning them. Those practices that are taken for granted as creating and sustaining relatedness-from the everyday practices of commensality to the capacity to have children-were consistently negated. Negating consensual avenues of relatedness did not leave these people in a void. On the contrary, new and productive meanings and experiences of being related were created and people entered into a relationship with anorexia that, in turn, tempered their relationships with their everyday worlds. In examining the 'relational matrix' of anorexia, new spaces of agency, ambiguity and power are illuminated. PMID- 26868612 TI - Sacred Groves of Parinche Valley of Pune District of Maharashtra, India and their Importance. AB - Sacred groves are protected areas of forests because of religious beliefs and constitute an important aspect of the cultural life of various communities throughout the world. The source of this culture can be traced back to prehistoric times. The sacred groves of Parinche valley, Pune district of Maharashtra, India were studied to understand their status and importance in relation to common natural resource bases and cultural aspects. Through formal interviews and non-participatory observation undertaken in all seasons between October 2002 and February 2004, 14 sacred groves were documented. Both EMIC and ETIC dimensions were incorporated in the choice of subjects. The results show that they are important for various communities as a common natural resource base. They promote cultural bonding among various communities and maintain harmony in social life. This can be evidenced during annual village festivals and family celebrations, which invariably take place within the premises of sacred groves. They are also important for biodiversity as many groves function like mini sanctuaries and harbour endemic and threatened plant species. The natural vegetation of the groves comprises many medicinal plants that are regularly harvested by local medicine men ( Vaidus ). Water is a precious resource, especially during summer months, and the perennial water sources that are present in the sacred groves are the only remaining water sources for seven villages. There is a compunction, on the other hand, of the sacred groves being influenced by urbanization, resulting in the building of concrete temples by clearing natural vegetation and planting ornamental and other economically useful trees in the cleared areas of the groves. Such actions alter these fragile ecosystems and deplete or destroy the natural resource base for which this ancient culture is believed to have been originally evolved. We conclude here that sacred groves were originally a common natural resource which were assimilated into the social and cultural life of villages in the Parinche valley. Hence their protection and enhancement should become part of village and forest planning. PMID- 26868613 TI - Experiences of Tensions in Re-orienting Selves: Tamil Refugees in Northern Norway Seeking Medical Advice. AB - Research among refugee populations tends to focus on the dramas of war and trauma. This paper instead brings attention to the more mundane everyday aspects of Tamil refugee resettlement in a fishing village along the arctic coast of Norway. Here, many Tamils experience various diffuse aches and pains that the local health personnel find difficult to diagnose and treat. In response to the difficulties, this study aims to investigate health and sickness as embedded in social life and cultural values. Data were generated during two different fieldwork periods: between 1996 and 1999 the author did short field visits in the region and conducted in-depth interviews and participant observation amongst Tamils and local health care workers, including observing health care consultations; and between September 1999 and September 2000 intensive fieldwork was undertaken amongst Tamil refugees in a small fishing village. A sample of two case studies illustrates Tamils' experience of being misunderstood as individuals and overlooked as social persons. Rather than looking at illness as symptoms of physiological or psychological malfunctions, the article suggests an understanding that allows an active, perceptive body and views the self as an orienting point of 'being in the world'. The Tamils are seen to live in a tension in which the self and the body are forced to re-orient themselves in the new social world. Tamils' illnesses are thus proposed rather to express a challenge and collapse in habituated patterns for constituting meaning and social practices. PMID- 26868614 TI - Enhanced contrast and depth resolution in polarization imaging using elliptically polarized light. AB - Polarization gating is a popular and widely used technique in biomedical optics to sense superficial tissues (colinear detection), deeper volumes (crosslinear detection), and also selectively probe subsuperficial volumes (using elliptically polarized light). As opposed to the conventional linearly polarized illumination, we propose a new protocol of polarization gating that combines coelliptical and counter-elliptical measurements to selectively enhance the contrast of the images. This new method of eliminating multiple-scattered components from the images shows that it is possible to retrieve a greater signal and a better contrast for subsurface structures. In vivo experiments were performed on skin abnormalities of volunteers to confirm the results of the subtraction method and access subsurface information. PMID- 26868615 TI - Silencing of the tomato phosphatidylinositol-phospholipase C2 (SlPLC2) reduces plant susceptibility to Botrytis cinerea. AB - The tomato [Solanum lycopersicum (Sl)] phosphatidylinositol-phospholipase C (PI PLC) gene family is composed of six members, named SlPLC1 to SlPLC6, differentially regulated on pathogen attack. We have previously shown that the fungal elicitor xylanase induces a raise of SlPLC2 and SlPLC5 transcripts and that SlPLC2, but not SlPLC5, is required for xylanase-induced expression of defense-related genes. In this work we studied the role of SlPLC2 in the interaction between tomato and the necrotrophic fungus Botrytis cinerea. Inoculation of tomato leaves with B. cinerea increases SlPLC2 transcript levels. We knocked-down the expression of SlPLC2 by virus-induced gene silencing and plant defense responses were analyzed upon B. cinerea inoculation. SlPLC2 silenced plants developed smaller necrotic lesions concomitantly with less proliferation of the fungus. Silencing of SlPLC2 resulted as well in a reduced production of reactive oxygen species. Upon B. cinerea inoculation, transcript levels of the salicylic acid (SA)-defense pathway marker gene SlPR1a were diminished in SlPLC2 silenced plants compared to non-silenced infected plants, while transcripts of the jasmonic acid (JA)-defense gene markers Proteinase Inhibitor I and II (SlPI-I and SlPI-II) were increased. This implies that SlPLC2 participates in plant susceptibility to B. cinerea. PMID- 26868617 TI - Database Extraction of Metabolite Information of Drug Candidates: Analysis of 27 AstraZeneca Compounds with Human Absorption, Distribution, Metabolism, and Excretion Data. AB - As part of the drug discovery and development process, it is important to understand the human metabolism of a candidate drug prior to clinical studies. Preclinical in vitro and in vivo experiments across species are conducted to build knowledge concerning human circulating metabolites in preparation for clinical studies; therefore, the quality of these experiments is critical. Within AstraZeneca, all metabolite identification (Met-ID) information is stored in a global database using ACDLabs software. In this study, the Met-ID information derived from in vitro and in vivo studies for 27 AstraZeneca drug candidates that underwent human absorption, distribution, metabolism, and excretion studies was extracted from the database. The retrospective analysis showed that 81% of human circulating metabolites were previously observed in preclinical in vitro and/or in vivo experiments. A detailed analysis was carried out to understand which human circulating metabolites were not captured in the preclinical experiments. Metabolites observed in human hepatocytes and rat plasma but not seen in circulation in humans (extraneous metabolites) were also investigated. The majority of human specific circulating metabolites derive from multistep biotransformation reactions that may not be observed in in vitro studies within the limited time frame in which cryopreserved hepatocytes are active. Factors leading to the formation of extraneous metabolites in preclinical studies seemed to be related to species differences with respect to transporter activity, secondary metabolism, and enzyme kinetics. This retrospective analysis assesses the predictive value of Met-ID experiments and improves our ability to discriminate between metabolites expected to circulate in humans and irrelevant metabolites seen in preclinical studies. PMID- 26868618 TI - Integrin Receptors Play a Key Role in the Regulation of Hepatic CYP3A. AB - Landmark studies describing the effect of microbial infection on the expression and activity of hepatic CYP3A used bacterial lipopolysaccharide as a model antigen. Our efforts to determine whether these findings were translatable to viral infections led us to observations suggesting that engagement of integrin receptors is key in the initiation of processes responsible for changes in hepatic CYP3A4 during infection and inflammation. Studies outlined in this article were designed to evaluate whether engagement of integrins, receptors commonly used by a variety of microbes to enter cellular targets, is vital in the regulation of CYP3A in the presence and absence of virus infection. Mice infected with a recombinant adenovirus (AdlacZ) experienced a 70% reduction in hepatic CYP3A catalytic activity. Infection with a mutant virus with integrin-binding arginine-glycine-aspartic acid (RGD) sequences deleted from the penton base protein of the virus capsid (AdDeltaRGD) did not alter CYP3A activity. CYP3A mRNA and protein levels in AdlacZ-treated animals were also suppressed, whereas those of mice given AdDeltaRGD were not significantly different from uninfected control mice. Silencing of the integrinbeta-subunit reverted adenovirus-mediated CYP3A4 suppression in vitro. Silencing of thealpha-subunit did not. Suppression of integrin subunits had a profound effect on nuclear receptors pregnane X receptor and constitutive androstane receptor, whereas retinoid X receptoralphawas largely unaffected. To our knowledge, this is the first time that extracellular receptors, like integrins, have been indicated in the regulation of CYP3A. This finding has several implications owing to the important role of integrins in normal physiologic process and in many disease states. PMID- 26868619 TI - Rumen microbial abundance and fermentation profile during severe subacute ruminal acidosis and its modulation by plant derived alkaloids in vitro. AB - Rumen microbiota have important metabolic functions for the host animal. This study aimed at characterizing changes in rumen microbial abundances and fermentation profiles using a severe subacute ruminal acidosis (SARA) in vitro model, and to evaluate a potential modulatory role of plant derived alkaloids (PDA), containing quaternary benzophenanthridine and protopine alkaloids, of which sanguinarine and chelerythrine were the major bioactive compounds. Induction of severe SARA strongly affected the rumen microbial composition and fermentation variables without suppressing the abundance of total bacteria. Protozoa and fungi were more sensitive to the low ruminal pH condition than bacteria. Induction of severe SARA clearly depressed degradation of fiber (P < 0.001), which came along with a decreased relative abundance of fibrolytic Ruminococcus albus and Fibrobacter succinogenes (P < 0.001). Under severe SARA conditions, the genus Prevotella, Lactobacillus group, Megasphaera elsdenii, and Entodinium spp. (P < 0.001) were more abundant, whereas Ruminobacter amylophilus was less abundant. SARA largely suppressed methane formation (-70%, P < 0.001), although total methanogenic 16S rRNA gene abundance was not affected. According to principal component analysis, Methanobrevibacter spp. correlated to methane concentration. Addition of PDA modulated ruminal fermentation under normal conditions such as enhanced (P < 0.05) concentration of total SCFA, propionate and valerate, and increased (P < 0.05) degradation of crude protein compared with the unsupplemented control diet. Our results indicate strong shifts in the microbial community during severe SARA compared to normal conditions. Supplementation of PDA positively modulates ruminal fermentation under normal ruminal pH conditions. PMID- 26868616 TI - Contributions of immunoaffinity chromatography to deep proteome profiling of human biofluids. AB - Human biofluids, especially blood plasma or serum, hold great potential as the sources of candidate biomarkers for various diseases; however, the enormous dynamic range of protein concentrations in biofluids represents a significant analytical challenge for detecting promising low-abundance proteins. Over the last decade, various immunoaffinity chromatographic methods have been developed and routinely applied for separating low-abundance proteins from the high- and moderate-abundance proteins, thus enabling much more effective detection of low abundance proteins. Herein, we review the advances of immunoaffinity separation methods and their contributions to the proteomic applications in human biofluids. The limitations and future perspectives of immunoaffinity separation methods are also discussed. PMID- 26868621 TI - Chronic pulmonary aspergillosis: help is on the way. PMID- 26868620 TI - Association of Radiation Dose to the Eyes With the Risk for Cataract After Nonretinoblastoma Solid Cancers in Childhood. AB - IMPORTANCE: Few studies have been published on the association of the radiation dose received to the eyes during radiotherapy (RT) for childhood cancer and the risk for later cataract. OBJECTIVE: To investigate the risk for cataract after treatment of nonretinoblastoma solid cancer in childhood. DESIGN, SETTING, AND PARTICIPANTS: The study used data from the Euro2K cohort that includes 4389 5 year survivors of solid tumors treated from January 1, 1945, to December 31, 1985; of these, 3172 patients were treated in France. A self-reported questionnaire was sent to French survivors from September 1, 2005, to December 31, 2012, when follow-up was considered completed for this study. However, 619 patients died before the beginning of the study and 128 patients treated for a retinoblastoma or who underwent enucleation were excluded. Likewise, 429 patients with unknown addresses or who did not return the consent form and 163 nonresponders did not participate. The remaining 1833 patients who completed the questionnaire underwent analysis for this study from June 1, 2014, to December 7, 2015. MAIN OUTCOMES AND MEASURES: Radiation doses in both eyes for individuals were estimated for all patients who had received RT. The role of the radiation dose in cataract risk was investigated using the Cox proportional hazard regression model and the excess relative or the absolute risk model. The role of ctytotoxic chemotherapy was also investigated. RESULTS: The 1833 patients (961 men [52.4%]; 872 women [47.6%]; mean [SD] age, 37.0 [8.5]) who returned the questionnaire were included in the analysis. After a mean follow-up of 32 years, 33 patients with unilateral or bilateral cataract were identified, for a total of 47 cataract events. The 47 events were validated by medical record review and by contacting the patients and the corresponding medical physician or ophthalmologist to obtain copies of diagnostic examinations or surgical reports. Overall, in a multivariable Cox proportional hazard regression analysis, patients who received RT had a 4.4-fold (95% CI, 1.5- to 13.0-fold) increased risk for cataract compared with patients who did not receive RT. Exposure to radiation doses of at least 10 Gy to the eyes increased the hazard ratio 39-fold (95% CI, 12.0- to 127.9-fold), relative to no radiation exposure. Although based on few patients, a strong increase in cataract risk (hazard ratio, 26.3; 95% CI, 7.1 96.6) was observed in patients treated with melphalan hydrochloride. CONCLUSIONS AND RELEVANCE: This study can inform guideline-based recommendations for long term follow-up for cataract. PMID- 26868622 TI - Of mice and men-the curious tale of beta blockers in asthma. PMID- 26868625 TI - Respiratory health in Poland. PMID- 26868624 TI - Knowledge gaps in therapeutic and non-therapeutic research on the Middle East respiratory syndrome. PMID- 26868623 TI - Treatment of cystic fibrosis in low-income countries. PMID- 26868626 TI - A voice for the silent. PMID- 26868627 TI - More targeted tuberculosis screening for immigrants? PMID- 26868628 TI - Take a deep breath in. PMID- 26868629 TI - Integrated Care Pathways for Airway Diseases. PMID- 26868630 TI - Prevalence of sleep apnoea syndrome in the middle to old age general population. PMID- 26868631 TI - Simple versus complex COPD: implications for health-care management. PMID- 26868632 TI - Prevalence and breed predisposition for thoracolumbar intervertebral disc disease in cats. AB - Objectives The objective was to evaluate the prevalence and possible breed predilections for thoracolumbar intervertebral disc disease (IVDD) in cats. Methods Medical records and imaging studies of cats diagnosed with thoracolumbar IVDD between January 2008 and August 2014 were retrospectively reviewed and compared with the general hospital population. The association between type of IVDD (ie, intervertebral disc extrusion [IVDE] or intervertebral disc protrusion [IVDP]) and breed, age, sex, and duration and severity of clinical signs was also evaluated. Results Of 12,900 cats presented during the study period, 31 (0.24%) were diagnosed with IVDD, including 17 purebred and 14 non-purebred cats. Of all presented purebred cats, 0.52% were diagnosed with thoracolumbar IVDD. More specifically, 1.29% of all British Shorthairs and 1.83% of all presented Persians were diagnosed with IVDD. Compared with the general hospital population, purebred cats ( P = 0.0001), British Shorthairs ( P <0.0001) and Persians ( P = 0.0006) were significantly overrepresented with thoracolumbar IVDD. Affected purebred cats were younger than affected non-purebred cats ( P = 0.02). Of 31 cats with IVDD, 19 were diagnosed with IVDE and 12 with IVDP. Cats with IVDE had a significantly shorter duration of clinical signs ( P = 0.0002) and demonstrated more severe neurological deficits ( P = 0.04) than cats with IVDP. Conclusions and relevance Although thoracolumbar IVDD is an uncommon condition in cats, purebred cats, British Shorthairs and Persians, were overrepresented. It is currently unclear if this represents a true breed predisposition or a higher likelihood of owners of purebred cats seeking referral for advanced diagnostic imaging procedures. PMID- 26868633 TI - Lack of Dystrophin Affects Bronchial Epithelium in mdx Mice. AB - Mild exercise training may positively affect the course of Duchenne Muscular Dystrophy (DMD). Training causes mild bronchial epithelial injury in both humans and mice, but no study assessed the effects of exercise in mdx mice, a well known model of DMD. The airway epithelium was examined in mdx (C57BL/10ScSn-Dmdmdx) mice, and in wild type (WT, C57BL/10ScSc) mice either under sedentary conditions (mdx-SD, WT-SD) or during mild exercise training (mdx-EX, WT-EX). At baseline, and after 30 and 45 days of training (5 d/wk for 6 weeks), epithelial morphology and markers of regeneration, apoptosis, and cellular stress were assessed. The number of goblet cells in bronchial epithelium was much lower in mdx than in WT mice under all conditions. At 30 days, epithelial regeneration (PCNA positive cells) was higher in EX than SD animals in both groups; however, at 45 days, epithelial regeneration decreased in mdx mice irrespective of training, and the percentage of apoptotic (TUNEL positive) cells was higher in mdx-EX than in WT-EX mice. Epithelial expression of HSP60 (marker of stress) progressively decreased, and inversely correlated with epithelial apoptosis (r = -0.66, P = 0.01) only in mdx mice. Lack of dystrophin in mdx mice appears associated with defective epithelial differentiation, and transient epithelial regeneration during mild exercise training. Hence, lack of dystrophin might impair repair in bronchial epithelium, with potential clinical consequences in DMD patients. J. Cell. Physiol. 231: 2218-2223, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26868634 TI - Prediction of treatment efficacy for prostate cancer using a mathematical model. AB - Prostate immune system plays a critical role in the regulation of prostate cancer development regarding androgen-deprivation therapy (ADT) and/or immunotherapy (vaccination). In this study, we developed a mathematical model to explore the interactions between prostate tumor and immune microenvironment. This model was used to predict treatment outcomes for prostate cancer with ADT, vaccination, Treg depletion and/or IL-2 neutralization. Animal data were used to guide construction, parameter selection, and validation of our model. Our analysis shows that Treg depletion and/or IL-2 neutralization can effectively improve the treatment efficacy of combined therapy with ADT and vaccination. Treg depletion has a higher synergetic effect than that from IL-2 neutralization. This study highlights a potential therapeutic strategy in effectively managing prostate tumor growth and provides a framework of systems biology approach in studying tumor-related immune mechanism and consequent selection of therapeutic regimens. PMID- 26868635 TI - Flavobacterium suaedae sp. nov., an endophyte isolated from the root of Suaeda corniculata. AB - A Gram-stain-negative, non-motile, yellow, endophytic bacterium, designated G16 7T, was isolated from the root of Suaeda corniculata in Inner Mongolia, northern China. Phylogenetic analysis, based on the 16S rRNA gene, revealed that strain G16-7T belonged to the genus Flavobacterium, with highest sequence similarities to Flavobacterium rakeshii FCS-5T, Flavobacterium suzhouense XIN-1T, Flavobacterium beibuense F44-8T, Flavobacterium hauense BX12T and Flavobacterium shanxiense YF-2, ranging from 92.7 % to 94.9 %. The predominant fatty acids of strain G16-7T were iso-C15 : 0, summed feature 3 (consisting of C16 : 1omega7c and/or C16 : 1omega6c), iso-C17 : 0 3-OH and summed feature 9 (consisting of iso C17 : 1omega9c and/or C16 : 0 10-methyl), while MK-6 was the major respiratory quinone. The major polar lipids were phosphatidylethanolamine, an unknown phospholipid, an unknown aminophospholipid, four unknown aminolipids and three unknown lipids. The genomic DNA G+C content of the strain was 34.2 mol%. Based on the phenotypic and genotypic characteristics, strain G16-7T is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium suaedae sp. nov. is proposed. The type strain is G16-7T ( = CGMCC 1.15461T = KCTC 42947T). PMID- 26868637 TI - Alcohols at the aqueous surface: chain length and isomer effects. AB - Surface-active organic molecules at the liquid-vapor interface are of great importance in atmospheric science. Therefore, we studied the surface behavior of alcohol isomers with different chain lengths (C4-C6) in aqueous solution with surface- and chemically sensitive X-ray photoelectron spectroscopy (XPS), which reveals information about the surface structure on a molecular level. Gibbs free energies of adsorption and surface concentrations are determined from the XPS results using a standard Langmuir adsorption isotherm model. The free energies of adsorption, ranging from around -15 to -19 kJ mol(-1) (C4-C6), scale linearly with the number of carbon atoms within the alcohols with DeltaGAds per -CH2-~-2 kJ mol(-1). While for the linear alcohols, surface concentrations lie around 2.4 * 10(14) molecules per cm(2) at the bulk concentrations where monolayers are formed, the studied branched alcohols show lower surface concentrations of around 1.6 * 10(14) molecules per cm(2), both of which are in line with the molecular structure and their orientation at the interface. Interestingly, we find that there is a maximum in the surface enrichment factor for linear alcohols at low concentrations, which is not observed for the shorter branched alcohols. This is interpreted in terms of a cooperative effect, which we suggest to be the result of more effective van der Waals interactions between the linear alcohol alkyl chains at the aqueous surface, making it energetically even more favorable to reside at the liquid-vapor interface. PMID- 26868636 TI - Autoantibodies directed to centromere protein F in a patient with BRCA1 gene mutation. AB - BACKGROUND: Autoantibodies directed to centromere protein F were first reported in 1993 and their association with malignancy has been well documented. CASE: We present the case of a 48-year-old Caucasian female with a BRCA1 gene mutation associated with bilateral breast cancer. Antinuclear autoantibody immunofluorescence performed for workup of possible inflammatory arthropathy showed a high titre cell cycle related nuclear speckled pattern, with subsequent confirmation by addressable laser bead immunoassay of the target antigen as an immunodominant epitope at the C-terminus of centromere protein F. CONCLUSION: Here we review the current literature on centromere protein F, its association with breast cancer and present the first case of this antibody being identified in a person with a BRCA1 gene mutation. PMID- 26868638 TI - Room temperature spin valve effect in NiFe/WS2/Co junctions. AB - The two-dimensional (2D) layered electronic materials of transition metal dichalcogenides (TMDCs) have been recently proposed as an emerging canddiate for spintronic applications. Here, we report the exfoliated single layer WS2 intelayer based spin valve effect in NiFe/WS2/Co junction from room temperature to 4.2 K. The ratio of relative magnetoresistance in spin valve effect increases from 0.18% at room temperature to 0.47% at 4.2 K. We observed that the junction resistance decreases monotonically as temperature is lowered. These results revealed that semiconducting WS2 thin film works as a metallic conducting interlayer between NiFe and Co electrodes. PMID- 26868639 TI - Identification of human exercise-induced physiological function changes based on bioinformatics analysis. AB - BACKGROUND: This study aimed to explore the physiological functions that were significantly affected by the exercise training. METHODS: Microarray dataset of GSE53598 was downloaded and preprocessed to identify the differentially expressed genes (DEGs) between pre- and post-exercise muscle biopsies. Then hierarchical clustering, protein-protein interaction (PPI) network construction and functional enrichment analysis were conducted. Finally, the significant physiological functions were identified using logistic regression algorithm. RESULTS: Total 420 up- and 420 down-regulated DEGs were identified. DEGs including E2F transcription factor 6, hypocretin (Orexin) neuropeptide precursor, caveolin 1, platelet derived growth factor beta polypeptide, and transforming growth factor, beta 1 had higher degree in the PPI network. Functions related to blood vessel development, regulation of cell migration, negative regulation of gene expression, and negative regulation of metabolic process changed significantly after exercise. CONCLUSIONS: Functions related to blood vessel development, regulation of cell migration, negative regulation of gene expression and negative regulation of metabolic process may be closely associated with exercising. PMID- 26868640 TI - Technical and physical determinants of soccer match-play performance in elite youth soccer players. AB - BACKGROUND: The aim of this study was to evaluate whether physical performance characteristics could be a better predictor than technical skills in determining the technical level of county soccer players in a match situation. METHODS: With institutional ethics approval, 25 male youth soccer players aged 16-18.5 years from a professional soccer academy in South East Asia were selected and height and body mass were recorded. Players were tested for sexual maturity (pubertal development scale [PDS] self-assessment), aerobic capacity (yo-yo intermittent recovery test level 1 [YYIR1]), repeated sprint ability (7 x 35 m sprints) acceleration (15 m sprint) and four soccer skills tests (dribble with pass, dribbling speed, passing and shooting accuracy). Players' technical ability during match play was assessed in small-sided games of soccer (5 v 5) using a novel game technical scoring chart (scoring chart completed by coaches to assess technical performance in a match situation) developed from criteria (e.g., first touch, dribbling and two footedness) used by youth soccer coaches for talent identification. RESULTS: A Spearman's rank correlation showed the YYIR1 test and 15 m sprint test were limited in predicting technical match performance (r=0.03, P=0.88, r=-0.23, P=0.32 respectively). A Pearson product moment correlation showed that the repeated sprint test was also limited in predicting technical match performance (r=-0.34, P=0.14). A dribbling skill with a pass was found to be the best determinant of a player's technical ability in a match (r=-0.57, P=0.00). CONCLUSIONS: Talent identification and selection programs in Asian youth soccer should include a dribbling skill performed with a pass. PMID- 26868641 TI - One night of partial sleep deprivation increased biomarkers of muscle and cardiac injuries during acute intermittent exercise. AB - BACKGROUND: The aim of this study was to evaluate the effect of two types of partial sleep deprivation (PSD) on biomarkers of muscle and cardiac injuries in response to acute intermittent exercise in professional athletes. METHODS: In a counterbalanced order, ten healthy male Taekwondo athletes were asked to perform the Yo-Yo Intermittent Recovery Test (YYIRT) in three conditions, allowing a 36 h recovery period in between: 1) following a full night of habitual sleep known as a reference sleep night (RN); 2) following PSD in the beginning of the night (PSDBN); and 3) following PSD in the end of the night (PSDEN). Heart rate (HR) and arterial oxygen saturation (SaO2) were measured during exercise. Blood samples were taken just before and 3 min after the YYIRT to measure biomarkers related to muscle and cardiac injuries (BRMCI). RESULTS: No significant effect of PSD was observed for physiological parameters (i.e., HR and SaO2). However, a significant alteration of resting ultra-sensitive C-reactive protein (us-CRP) (P<0.05) and myoglobin (MYO) (P<0.01) levels was detected after PSDEN. Furthermore, all BRMCI were altered by exercise. Likewise, compared to RN, PSD affected creatine phosphokinase (CPK) and MYO levels in response to exercise (P<0.05). CONCLUSIONS: The present study indicates that PSDEN increase the resting us-CRP and MYO levels, and that the two types of PSD increase the CPK and MYO levels in response to acute intermittent exercise, among Taekwondo athletes, in the evening of the following day. However, no rise of the physiological responses has been observed after the two types of PSD, at rest and in response to the exercise. PMID- 26868642 TI - Critical load: a novel approach to determining a sustainable intensity during resistance exercise. AB - BACKGROUND: A hyperbolic function as well as a linear relationship between power output and time to exhaustion (Tlim) has been consistently observed during dynamic non-resistive exercises. However, little is known about its concept to resistance exercises (RE), which could be defined as critical load (CL). This study aimed to verify the existence of CL during dynamic RE and to verify the number of workbouts necessary to determine the optimal modeling to achieve it. METHODS: Fifteen healthy men (23+/-2.5 yrs) completed 1 repetition maximum test (1RM) on a leg press and 3 (60%, 75% and 90% of 1RM) or 4 (+ 30% of 1RM) workbouts protocols to obtain the CL by hyperbolic and linear regression models between Tlim and load performed. Blood lactate and leg fatigue were also measured. RESULTS: CL was obtained during RE and 3 workbouts protocol estimate it at 53% while 4 tests at 38% of 1 RM. However, based on coefficients of determination, 3 protocols provided a better fit than the 4-parameter model, respectively (R2>0.95 vs. >0.77). Moreover, all intensities increased blood lactate and leg fatigue, however, when corrected by Tlim, were significantly lower at CL. CONCLUSIONS: It was possible to determinate CL during dynamic lower limbs RE and that 3 exhaustive workbouts can be used to better estimate the CL, constituting a new concept of determining this threshold during dynamic RE and reducing the physically demanding nature of the protocol. These findings may have important applications for functional performance evaluation and prescription of RE programs. PMID- 26868643 TI - Interrelationship Between Organizational and Relational Aspects and the Return-to Work Process: A Case Study with Nursing Professionals at a Teaching Hospital in Brazil. AB - Introduction The process of returning to work, especially for individuals with labor restrictions, impacts work teams and interferes with the labor reinsertion process. In this study, we aimed to understand the impact of these situations on a nursing team from both organizational and relational perspectives. Methods We conducted a qualitative research study at a university hospital in the municipality of Sao Paulo using three strategies: documentary analysis; semi structured interviews with pairs of workers returning to a labor situation; and a focus group with nursing managers. Results Medical leaves of absence overburden the employees who remain working. Regarding the return to work, the participants reported both positive and negative aspects. One positive aspect reported was that those who return to work contribute to the division of labor, generating solidarity and cooperation. The negative aspects reported were related to the return of workers with labor restrictions who do not fully resume their activities, consequently generating conflicts within the work teams that interfere with the reintegration processes. The supervisors reported difficulties reorganizing work on a broad scale and assessing the workers' diagnoses and symptoms and the workers themselves in terms of the necessity of their leaves and the validity of their labor restrictions. Conclusion The organization of labor and social relationships among peers and supervisors is a significant contributor to the success or failure of the work reintegration process and therefore should be considered. We aimed to address this issue by highlighting the complexity of the return-to-work process among health workers. PMID- 26868644 TI - Cadmium Accumulation and Pathological Alterations in the Midgut Gland of Terrestrial Snail Helix pomatia L. from a Zinc Smelter Area: Role of Soil pH. AB - The purpose of this study was to determine whether cadmium (Cd) accumulation and toxicity in the midgut gland of Helix pomatia snails living in a Cd-contaminated area were related to soil pH. Toxic responses in the midgut gland (i.e., increased vacuolization and lipid peroxidation) occurred in H. pomatia snails exhibiting the highest Cd levels in the gland (265-274 ug/g dry wt) and living on acidic soil (pH 5.3-5.5), while no toxicity was observed in snails accumulating less Cd (90 ug/g) and ranging on neutral soil (pH 7.0), despite the fact that total soil Cd was similar in the two cases. The accumulation of Cd in the gland was directly related to the water extractable Cd in soil, which in turn correlated inversely with soil pH, indicating that this factor had a significant effect on tissue Cd. It appeared further that the occurrence of Cd toxicity was associated with low levels of metallothionein in the gland of snails ranging on acidic soil. PMID- 26868645 TI - Psychometric Properties of the Milestones of Recovery Scale-Older Adult Version. AB - The Milestones of Recovery Scale (MORS) is a tool that mental health professionals can use to track clients' recovery. It has been shown to have good reliability and validity in an adult population. It is important to demonstrate its psychometric properties among the elderly. This study assessed the reliability and validity of the MORS among a multi-ethnic (52 % White) sample of adults 54 and older (M = 67) at several mental health agencies in California. The clients, N = 432, were assessed by two raters each at two time points 2 weeks apart. Ratings were obtained on the MORS, the modified Global Assessment of Functioning scale (mGAF), and the Multnomah Community Ability Scale (MCAS). The MORS demonstrated acceptable reliability: inter-rater r = .65 and test-retest r = .71; the mGAF was .56 and .79; the MCAS was .66 and .85. The validity of the MORS was also supported: mGAF-MORS r = .68 and MCAS-MORS r = .74. This study lends support for the use of the MORS in older adult populations. In addition, this is the first report of the psychometric properties of the MCAS with an entirely older adult sample. PMID- 26868646 TI - Are Users Satisfied with Assertive Community Treatment in Spite of Personal Restrictions? AB - The purpose of this explorative study was to examine satisfaction among 70 users of 12 Norwegian Assertive Community Treatment teams. The study was carried out among a group of 70 service users, and reveals generally high levels of satisfaction with the service, with satisfaction also being high in comparison to other ACT satisfaction studies. Users under a Community Treatment Order were more satisfied, while users with an alcohol use disorder were less satisfied. Younger service users were less positive than older users. There was no difference in satisfaction between the genders. This study's positive result may reflect the ACT model's focus on user involvement, recovery and building relationships, and the fact that this service has a more holistic approach than previous services that users have experienced. PMID- 26868647 TI - A prospective study of two isothermal amplification assays compared with real time PCR, CCNA and toxigenic culture for the diagnosis of Clostridium difficile infection. AB - BACKGROUND: New molecular methods of detecting Clostridium difficile infection (CDI) provide the routine lab with a sensitive random access method to produce results that are available in a shorter time than traditional methods. METHODS: In this prospective study a total of 989 stool specimens were tested over a period of 16 months in parallel using two isothermal amplification assays, AmpliVue(r) (Quidel) and Illumigene(r) (Meridian) and the results compared to those from toxigenic culture. In addition all specimens were tested using a cytotoxic cell neutralisation assay (CCNA) and three different Real-time PCR targeting a C. difficile-specific 16S rDNA sequence or the toxin genes tcdA, tcdB/tcdB027 or cdtB. RESULTS: AmpliVue(r) was positive in 242 (24.5%) and Illumigene(r) in 228 (23.1%) specimens. 167 (16.9%) specimens were positive in toxigenic culture. Real-time-tcdA and -tcdB PCR was positive in 211 (21.3%) specimens, Real-time-cdtB PCR was positive in 101 (10.2%) specimens and C. difficile-PCR (16S rDNA) in 267 (27.0%) specimens. CONCLUSIONS: The respective sensitivity, specificity, positive predictive value and negative predictive value compared to toxigenic culture were 91, 89, 62 and 98% for AmpliVue(r) and 91, 91, 67 and 98% for Illumigene(r). PMID- 26868649 TI - Approaching a universal scaling relationship between fracture stiffness and fluid flow. AB - A goal of subsurface geophysical monitoring is the detection and characterization of fracture alterations that affect the hydraulic integrity of a site. Achievement of this goal requires a link between the mechanical and hydraulic properties of a fracture. Here we present a scaling relationship between fluid flow and fracture-specific stiffness that approaches universality. Fracture specific stiffness is a mechanical property dependent on fracture geometry that can be monitored remotely using seismic techniques. A Monte Carlo numerical approach demonstrates that a scaling relationship exists between flow and stiffness for fractures with strongly correlated aperture distributions, and continues to hold for fractures deformed by applied stress and by chemical erosion as well. This new scaling relationship provides a foundation for simulating changes in fracture behaviour as a function of stress or depth in the Earth and will aid risk assessment of the hydraulic integrity of subsurface sites. PMID- 26868648 TI - Clinical efficacy of combination therapy with an alpha blocker and low-dose sildenafil on post-therapy lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer. AB - PURPOSE: To investigate the efficacy of tamsulosin monotherapy and tamsulosin with low-dose sildenafil combination therapy on lower urinary tract symptoms (LUTS) following low-dose-rate (LDR) brachytherapy in early prostate cancer patients. METHODS: From March 2008 to June 2014, of the 212 prostate cancer patients with a Gleason score <=7 who received LDR brachytherapy, 80 patients with a prostate volume <=35 g and progressed LUTS following implantation were selected. All 80 patients took tamsulosin 0.4-mg monotherapy until 1 month after implantation. Then, the patients were divided into two groups; 45 patients received tamsulosin 0.4-mg monotherapy, and 35 patients received tamsulosin 0.4 mg plus sildenafil 25-mg combination therapy due to erectile dysfunction. LUTS were compared between the two groups using the International Prostate Symptom Score (IPSS), the mean maximum flow rate (Q max) and the pre-implantation post voiding residual (PVR) volume at 1 and 3 months after implantation. RESULTS: The pre-implantation total IPSS, Q max and PVR for the monotherapy and combination therapy groups were 14.0 +/- 6.7, 14.3 +/- 3.2 ml/s and 36.3 +/- 16.7 ml and 15.3 +/- 5.6, 13.7 +/- 4.5 ml/s and 39.0 +/- 23.4 ml, respectively. At 1 month post implantation, both groups showed increases in total IPSS and PVR, but no statistically significant differences were observed (P = 0.078, P = 0.23). At 3 months post-implantation, the combination therapy group showed a greater decrease in total IPSS compared with the monotherapy group (P = 0.035), but there were no statistically significant differences in the Q max and PVR between the two groups. CONCLUSION: Tamsulosin plus low-dose sildenafil combination therapy is a beneficial treatment for post-implantation progression of LUTS. PMID- 26868650 TI - Development of a complex intervention to support the initiation of advance care planning by general practitioners in patients at risk of deteriorating or dying: a phase 0-1 study. AB - BACKGROUND: Most patients with life-limiting illnesses are treated and cared for over a long period of time in primary care and guidelines suggest that ACP discussions should be initiated in primary care. However, a practical model to implement ACP in general practice is lacking. Therefore, the objective of this study is to develop an intervention to support the initiation of ACP in general practice. METHODS: We conducted a Phase 0-I study according to the Medical Research Council (MRC) Framework. Phase 0 consisted of a systematic literature review about the barriers and facilitators for GPs to engage in ACP, focus groups with GPs were held about their experiences, attitudes and concerns regarding initiating ACP in general practice and a review of ACP interventions to identify potential components for the development of our intervention. In Phase 1, we developed a complex intervention to support the initiation of ACP in general practice in patients at risk of deteriorating or dying, based on the results of Phase 0. The complex intervention and its components were reviewed and refined by two expert panels. RESULTS: Phase 0 resulted in the identification of the factors inhibiting or enabling GPs' initiation of ACP and important components underpinning existing ACP interventions. Based on these findings, an intervention was developed in Phase 1 consisting of: (1) a training for GPs in initiating and conducting ACP discussions, (2) a register of patients eligible for ACP discussions, (3) an educational booklet on ACP for patients to prepare the ACP discussions that includes general information on ACP, a section on the role of GPs in the process of ACP and a prompt list, (4) a conversation guide to support GPs in the ACP discussions and (5) a structured documentation template to record the outcomes of discussions. CONCLUSION: Taking into account the barriers and facilitators for GPs to initiate ACP as well as the key factors underpinning successful ACP intervention in other health care settings, a complex intervention for general practice was developed, after gaining feedback from two expert panels. The feasibility and acceptability of the intervention will subsequently be tested in a Phase II study. PMID- 26868651 TI - Neozygites osornensis (Neozygitales: Neozygitaceae) Infecting Cinara sp. (Hemiptera: Aphididae) in Brazil. AB - The genus Neozygites has been known in Brazil until now only on mites, and this is its first report on aphids in Brazil. Tree-dwelling aphids (Cinara sp.) on a cypress tree were regularly monitored for entomopathogenic fungi in the city of Terezopolis de Goias in Central Brazil between July 2014 and April 2015. During the survey, mycosed aphids were found attached to twigs. The fungus was identified morphologically as Neozygites osornensis. No in vitro cultures were established from infected aphids. The finding reported here suggests that special attention should be paid in the future for the possible occurrences of Neozygites species wherever cinaran aphids occur around the globe. PMID- 26868652 TI - Characterization of Phenacoccus solenopsis (Tinsley) (Homoptera: Pseudococcidae) Resistance to Emamectin Benzoate: Cross-Resistance Patterns and Fitness Cost Analysis. AB - Cotton mealybug Phenacoccus solenopsis (Tinsley) (Homoptera: Pseudococcidae) is a sucking pest of worldwide importance causing huge losses by feeding upon cotton in various parts of the world. Because of the importance of this pest, this research was carried out to select emamectin resistance in P. solenopsis in the laboratory to study cross-resistance, stability, realized heritability, and fitness cost of emamectin resistance. After selection from third generation (G3) to G6, P. solenopsis developed very high emamectin resistance (159.24-fold) when compared to a susceptible unselected population (Unsel pop). Population selected to emamectin benzoate conferred moderate (45.81-fold), low (14.06-fold), and no cross-resistance with abamectin, cypermethrin, and profenofos, respectively compared to the Unsel pop. A significant decline in emamectin resistance was observed in the resistant population when not exposed to emamectin from G7 to G13. The estimated realized heritability (h (2)) for emamectin resistance was 0.84. A high fitness cost was associated with emamectin resistance in P. solenopsis. Results of this study may be helpful in devising insecticide resistance management strategies for P. solenopsis. PMID- 26868653 TI - Seasonal Life Cycle of Linepithema micans (Forel) (Hymenoptera: Formicidae) in Vineyards. AB - Linepithema micans (Forel) is considered to be the main ant species responsible for the spread of Eurhizococcus brasiliensis (Wille), a soil scale that damages vine plants in southern Brazil. In this work, the seasonal life cycle of L. micans was evaluated in vineyards to define the most appropriate time for the application of toxic baits for control. Ant nests were transported to the laboratory in plastic bags, and individual ants were separated into groups of eggs, larvae, pupae, workers, males, and queens, recording the number of individuals per colony. The seasonal life cycle of L. micans in the vineyards began in spring with the deposition of eggs by queens. During the warm months of the year (spring and summer), it was possible to observe nests consisting primarily of eggs and pupae. During the autumn and winter months, the colonies were composed predominantly of larvae and a reduction in eggs was observed. Because the main control strategy targets the larval stage of the insect, the application of toxic baits for the control of L. micans must be performed during the winter. PMID- 26868654 TI - Identification of the Female Sex Pheromone of the Leafroller Proeulia triquetra Obraztsov (Lepidoptera: Tortricidae). AB - Proeulia triquetra Obraztsov (Lepidoptera: Tortricidae) is an occasional pest in fruit orchards in central-southern Chile. In order to develop species-specific lures for detection and monitoring of this species, we identified the female produced sex pheromone. (Z)-11-Tetradecenyl acetate (Z11-14:OAc), (E)-9-dodecenyl acetate (E9-12:OAc), and (E)-11-Tetradecenyl acetate (E11-14:OAc) were identified as biologically active compounds present in female pheromone glands by solvent extraction of the gland and analysis of the extracts by gas chromatography electroantennographic detection and gas chromatography-mass spectrometry. In field tests, lures baited with synthetic Z11-14:OAc and E9-12:OAc in a 10:1 ratio were highly attractive to males of the species. PMID- 26868656 TI - Marginalization of Cultural Groups. PMID- 26868655 TI - Ruminococcus gnavus E1 modulates mucin expression and intestinal glycosylation. AB - AIMS: The molecular cross-talk between commensal bacteria and the gut play an important role in the maintenance of the intestinal homeostasis and general health. Here, we studied the impact of a major Gram-positive anaerobic bacterium of the human gut microbiota, that is, Ruminococcus gnavus on the glycosylation pattern and the production of intestinal mucus by the goblet cells. METHODS AND RESULTS: Our results showed that R. gnavus E1 specifically increases the expression and the glycosylation level of the intestinal glyco-conjugates by goblet cells in the colonic mucosa of mono-associated mice with R. gnavus E1 as well as in human HT29-MTX cells. Such an effect was mediated through induction of the level of mRNA encoding for the major intestinal gel-forming mucin such as MUC2 and various glycosyltransferase enzymes. CONCLUSIONS: This study demonstrates for the first time that R. gnavus E1 possess the ability to modulate the glycosylation profile of the glyco-conjugate molecules and mucus in goblet cells. SIGNIFICANCE AND IMPACT OF THE STUDY: Furthermore, we demonstrated that R. gnavus E1 modified specifically the glycosylation pattern and MUC2 expression by means of a small soluble factor of peptidic nature (<3 kDa) and heat stable in the HT29-MTX cell. PMID- 26868657 TI - President's Message: Transcultural Nursing in the Global Community. PMID- 26868658 TI - A Changing World Through the Lens of Panama. PMID- 26868659 TI - Microbiological diagnosis and molecular typing of Legionella strains during an outbreak of legionellosis in Southern Germany. AB - An explosive outbreak of Legionnaires' disease with 64 reported cases occurred in Ulm/Neu-Ulm in the South of Germany in December 2009/January 2010 caused by Legionella (L.) pneumophila serogroup 1, monoclonal (mAb) subtype Knoxville, sequence type (ST) 62. Here we present the clinical microbiological results from 51 patients who were diagnosed at the University hospital of Ulm, the results of the environmental investigations and of molecular typing of patients and environmental strains. All 50 patients from whom urine specimens were available were positive for L. pneumophila antigen when an enzyme-linked immunosorbent assay (EIA) was used following concentration of those urine samples that tested initially negative. The sensitivity of the BinaxNow rapid immunographic assay (ICA), after 15 min reading and after 60 min reading were 70% and 84%, respectively. Direct typing confirmed the monoclonal subtype Knoxville in 5 out of 8 concentrated urine samples. Real time PCR testing of respiratory tract specimens for L. pneumophila was positive in 15 out of 25 (60%) patients. Direct nested sequence based typing (nSBT) in some of these samples allowed partial confirmation of ST62. L. pneumophila serogroup 1, monoclonal subtype Knoxville ST62, defined as the epidemic strain was isolated from 8 out of 31 outbreak patients (26%) and from one cooling tower confirming it as the most likely source of the outbreak. While rapid detection of Legionella antigenuria was crucial for the recognition and management of the outbreak, culture and molecular typing of the strains from patients and environmental specimens was the clue for the rapid identification of the source of infection. PMID- 26868660 TI - Management of obesity. AB - A modern approach to obesity acknowledges the multifactorial determinants of weight gain and the health benefits to be derived from weight loss. Foundational to any weight loss effort is lifestyle change, diet, and increased physical activity. The approach should be a high quality diet to which patients will adhere accompanied by an exercise prescription describing frequency, intensity, type, and time with a minimum of 150 min moderate weekly activity. For patients who struggle with weight loss and who would receive health benefit from weight loss, management of medications that are contributing to weight gain and use of approved medications for chronic weight management along with lifestyle changes are appropriate. Medications approved in the USA or European Union are orlistat, naltrexone/bupropion, and liraglutide; in the USA, lorcaserin and phentermine/topiramate are also available. Surgical management (gastric banding, sleeve gastrectomy, and Roux-en Y gastric bypass) can produce remarkable health improvement and reduce mortality for patients with severe obesity. PMID- 26868661 TI - Clinical utility of transthoracic echocardiography for screening abdominal aortic aneurysm: a prospective study in a Japanese population. AB - BACKGROUND: The aim of the present study was to evaluate the clinical utility of transthoracic echocardiography (TTE) for screening abdominal aortic aneurysm (AAA) and to identify important TTE indices associated with AAA in a Japanese population. METHODS: We prospectively studied 1912 patients who were referred for TTE. AAA was defined as >= 30 mm in size. RESULTS: The abdominal aorta was visualized in 95.1% (1818/1912) by TTE. AAA was identified in 2.6% (47/1818). The aortic root size was significantly larger in patients with AAA than those without (36.0 +/- 4.1 vs. 31.7 +/- 4.2 mm, p < 0.001). The aortic root size had a fair correlation with abdominal aortic size (r = 0.31, p < 0.001). The aortic root size of >= 34 mm was predictive of AAA by receiver operating characteristic curve analysis (area under the curve = 0.78, p < 0.001). Multiple logistic regression analysis revealed that aortic root size (Hazard ratio 1.23, p < 0.001) and age (Hazard ratio 1.05, p = 0.013) were the independent predictors of AAA. CONCLUSIONS: The feasibility of the abdominal aortic visualization during TTE was excellent. The aortic root size measured by TTE was the independent predictor of AAA. Screening for AAA during TTE appeared to be useful especially in the older patients with a large (>=34 mm) aortic root. PMID- 26868662 TI - Development of action mirroring. PMID- 26868664 TI - SCA28: Novel Mutation in the AFG3L2 Proteolytic Domain Causes a Mild Cerebellar Syndrome with Selective Type-1 Muscle Fiber Atrophy. AB - The spinocerebellar ataxias (SCA) are a group of rare inherited neurodegenerative diseases characterized by slowly progressive cerebellar ataxia, resulting in unsteady gait, clumsiness, and dysarthria. The disorders are predominantly inherited in an autosomal dominant manner. Mutations in the gene AFG3L2 that encodes a subunit of the mitochondrial m-AAA protease have previously been shown to cause spinocerebellar ataxia type 28 (SCA28). Here, we present the clinical phenotypes of three patients from a family with autosomal dominant cerebellar ataxia and show by molecular genetics and in silico modelling that this is caused by a novel missense mutation in the AFG3L2 gene. Furthermore, we show, for the first time, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans of the brain and selective type I fiber atrophy of skeletal muscle of SCA28 patients indicating non-nervous-system involvement in SCA28 as well. PMID- 26868666 TI - Donor blood screening and moral responsibility: how safe should blood be? AB - Some screening tests for donor blood that are used by blood services to prevent transfusion-transmission of infectious diseases offer relatively few health benefits for the resources spent on them. Can good ethical arguments be provided for employing these tests nonetheless? This paper discusses-and ultimately rejects-three such arguments. According to the 'rule of rescue' argument, general standards for cost-effectiveness in healthcare may be ignored when rescuing identifiable individuals. The argument fails in this context, however, because we cannot identify beforehand who will benefit from additional blood screening tests. On the 'imposed risk' argument, general cost-effectiveness standards do not apply when healthcare interventions impose risks on patients. This argument ignores the fact that imposing risks on patients is inevitable in healthcare and that these risks can be countered only within reasonable limits. Finally, the 'manufacturing standard' argument premises that general cost-effectiveness standards do not apply to procedures preventing the contamination of manufactured medical products. We contend that while this argument seems reasonable insofar as commercially manufactured medical products are concerned, publicly funded blood screening tests should respect the standards for general healthcare. We conclude that these particular arguments are unpersuasive, and we offer directions to advance the debate. PMID- 26868665 TI - Atxn2 Knockout and CAG42-Knock-in Cerebellum Shows Similarly Dysregulated Expression in Calcium Homeostasis Pathway. AB - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited neurodegenerative disorder with preferential affection of Purkinje neurons, which are known as integrators of calcium currents. The expansion of a polyglutamine (polyQ) domain in the RNA-binding protein ataxin-2 (ATXN2) is responsible for this disease, but the causal roles of deficient ATXN2 functions versus aggregation toxicity are still under debate. Here, we studied mouse mutants with Atxn2 knockout (KO) regarding their cerebellar global transcriptome by microarray and RT-qPCR, in comparison with data from Atxn2-CAG42-knock-in (KIN) mouse cerebellum. Global expression downregulations involved lipid and growth signaling pathways in good agreement with previous data. As a novel effect, downregulations of key factors in calcium homeostasis pathways (the transcription factor Rora, transporters Itpr1 and Atp2a2, as well as regulator Inpp5a) were observed in the KO cerebellum, and some of them also occurred subtly early in KIN cerebellum. The ITPR1 protein levels were depleted from soluble fractions of cerebellum in both mutants, but accumulated in its membrane-associated form only in the SCA2 model. Coimmunoprecipitation demonstrated no association of ITPR1 with Q42-expanded or with wild-type ATXN2. These findings provide evidence that the physiological functions and protein interactions of ATXN2 are relevant for calcium-mediated excitation of Purkinje cells as well as for ATXN2-triggered neurotoxicity. These insights may help to understand pathogenesis and tissue specificity in SCA2 and other polyQ ataxias like SCA1, where inositol regulation of calcium flux and RORalpha play a role. PMID- 26868667 TI - Using contrast patterns between true complexes and random subgraphs in PPI networks to predict unknown protein complexes. AB - Most protein complex detection methods utilize unsupervised techniques to cluster densely connected nodes in a protein-protein interaction (PPI) network, in spite of the fact that many true complexes are not dense subgraphs. Supervised methods have been proposed recently, but they do not answer why a group of proteins are predicted as a complex, and they have not investigated how to detect new complexes of one species by training the model on the PPI data of another species. We propose a novel supervised method to address these issues. The key idea is to discover emerging patterns (EPs), a type of contrast pattern, which can clearly distinguish true complexes from random subgraphs in a PPI network. An integrative score of EPs is defined to measure how likely a subgraph of proteins can form a complex. New complexes thus can grow from our seed proteins by iteratively updating this score. The performance of our method is tested on eight benchmark PPI datasets and compared with seven unsupervised methods, two supervised and one semi-supervised methods under five standards to assess the quality of the predicted complexes. The results show that in most cases our method achieved a better performance, sometimes significantly. PMID- 26868669 TI - Erratum to: Genetic determination of height-mediated mate choice. PMID- 26868668 TI - Pulmonary complications of type 1 neurofibromatosis. AB - INTRODUCTION: Type 1 neurofibromatosis is one of the most common genetic diseases, with an incidence of 1/3500 live births. Its diagnosis primarily relies on the clinical features of the condition. CURRENT KNOWLEDGE: The life expectancy of these patients is reduced by 10 years, on average, compared to the general population. Type 1 neurofibromatosis has been shown to increase the risk of various types of neoplasia, primarily those affecting the neural crest. In addition, interstitial lung disease, lung cancer, and pulmonary hypertension have been observed during the third or the fourth decade of an adult's life. PERSPECTIVES: There are only few case reports available that address the pulmonary complications of neurofibromatosis type 1. It is thus crucial to fully understand this rare disease and its potential complications in order to allow for early diagnosis so we are able to improve the quality of life and survival of those suffering from the condition. CONCLUSIONS: The pulmonary complications of type 1 neurofibromatosis can be severe and life-threatening. Patients with this condition should thus undergo regular clinical visits and examinations to allow pulmonary complications to be detected and treatment to be initiated as early as possible. PMID- 26868670 TI - Induction of nephron progenitors and glomeruli from human pluripotent stem cells. AB - Studies of kidney regeneration using stem cells have progressed rapidly in recent years. Our group has developed a protocol to induce nephron progenitors from both mouse and human pluripotent stem cells which is based on a revised model of early stage kidney specification. The induced progenitors readily reconstitute three dimensional nephron structures, including glomeruli and renal tubules, in vitro. We can further generate human induced pluripotent stem cells (iPSCs), in which nephrin-expressing glomerular podocytes are tagged with green fluorescent protein (GFP). The sorted GFP-positive cells retain the podocyte-specific molecular and structural features. Upon transplantation, mouse endothelial cells of the host animals are integrated into the human iPSC-derived glomeruli, and the podocytes show further maturation. Other laboratories have reported different protocols to induce nephron structures from human iPSCs in vitro. These findings will accelerate our understanding of kidney development and diseases in humans. PMID- 26868672 TI - UK records four cases of Zika virus in past six weeks. PMID- 26868671 TI - Clinicopathological correlation of psychosis and brain vascular changes in Alzheimer's disease. AB - Psychosis is common in Alzheimer's disease (AD). However, studies on neuropathology in vascular etiology contributing to psychosis in AD is lacking to date. The aim of this study was to investigate neuropathological vascular related changes in Alzheimer's disease with psychosis. Data of patients with AD from the National Alzheimer's Coordinating Center between 2005 to September 2013 was accessed and reviewed. Presence of psychosis was determined based on Neuropsychiatric Inventory Questionnaire taken from the last visit within one year prior to death, and patients were divided into psychosis positive and negative group. Comparison of clinical details and neuropathological vascular changes between the groups was performed using Wilcoxon rank sum test and Chi square/ Fisher's exact test. Significant variables were further included in a multivariate logistic model. Overall, 145 patients was included. Of these, 50 patients were psychosis positive. Presence of one or more cortical microinfarcts and moderate to severe arteriosclerosis was found to be positively associated with psychosis. Our results suggest vascular changes correlate with psychosis in Alzheimer's disease. PMID- 26868673 TI - Dignity, Health, and Membership: Who Counts as One of Us? AB - This essay serves as an introduction to this issue of the Journal of Medicine and Philosophy. The five articles in this issue address a range of topics from the human embryo and substantial change to conceptions of disability. They engage claims of moral status, defense of our humanity, and argue for an accurate and just classification of persons of different communities within a healthcare system. I argue in this essay that though their concerns are diverse, the authors in this issue help to answer a common question: "Who counts as one of us?" Reading these articles through the lens of membership and the themes of dignity illustrates this commonality and bears fruit for further reflection on many of the challenging issues addressed in the subsequent papers. PMID- 26868674 TI - "There's nothing here": Deindustrialization as risk environment for overdose. AB - BACKGROUND: Applying the "risk environment" approach proposed by Rhodes (2002, 2009), this study considers the diverse contextual factors contributing to drug overdose in a deindustrialized region of the United States. The Monongahela Valley of Pennsylvania, once a global center of steel production, has suffered a mass exodus of jobs, residents, and businesses since a national manufacturing crisis erupted in the early 1980s; more recently, it has seen a dramatic uptick in accidental drug poisoning deaths. Where recent local and national media attention to overdose has focused on suburban areas and middle class victims, this study concentrates instead on the deteriorating mill city of McKeesport, Pennsylvania. METHODS: Eighteen clients of the city's sole drug treatment facility participated in in-depth interviews concerning their direct experience with accidental overdose. Specifically, participants were asked to describe their own most recent overdose event and/or the last overdose they had personally witnessed. They were also asked to speculate upon the roots of the local overdose epidemic, while venturing possible remedies. RESULTS: In relating their overdose experiences, participants characterized a micro-level risk environment that was hidden behind closed doors, and populated by unprepared, ambivalent overdose "assistants." Tasked with explaining a geographic concentration of overdose in and around McKeesport, interviewees referenced the hopelessness of the area and its lack of opportunity as driving the use of heroin, with many explicitly suggesting the need for jobs and community reinvestment to reduce fatalities. CONCLUSION: While state and county efforts to ameliorate overdose mortality have focused upon creating an open market in naloxone, this study suggests the need for interventions that address the poverty and social isolation of opiate users in the post-industrial periphery. PMID- 26868676 TI - Unraveling the mechanism of proton translocation in the extracellular half channel of bacteriorhodopsin. AB - Bacteriorhodopsin, a light activated protein that creates a proton gradient in halobacteria, has long served as a simple model of proton pumps. Within bacteriorhodopsin, several key sites undergo protonation changes during the photocycle, moving protons from the higher pH cytoplasm to the lower pH extracellular side. The mechanism underlying the long-range proton translocation between the central (the retinal Schiff base SB216, D85, and D212) and exit clusters (E194 and E204) remains elusive. To obtain a dynamic view of the key factors controlling proton translocation, a systematic study using molecular dynamics simulation was performed for eight bacteriorhodopsin models varying in retinal isomer and protonation states of the SB216, D85, D212, and E204. The side chain orientation of R82 is determined primarily by the protonation states of the residues in the EC. The side-chain reorientation of R82 modulates the hydrogen bond network and consequently possible pathways of proton transfer. Quantum mechanical intrinsic reaction coordinate calculations of proton-transfer in the methyl guanidinium-hydronium-hydroxide model system show that proton transfer via a guanidinium group requires an initial geometry permitting proton donation and acceptance by the same amine. In all the bacteriorhodopsin models, R82 can form proton wires with both the CC and the EC connected by the same amine. Alternatively, rare proton wires for proton transfer from the CC to the EC without involving R82 were found in an O' state where the proton on D85 is transferred to D212. PMID- 26868675 TI - Caffeine promotes wakefulness via dopamine signaling in Drosophila. AB - Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine. PMID- 26868677 TI - Prevalence of insomnia-related symptoms continues to increase in the Finnish working-age population. AB - In 2008, we published epidemiological data from 1972 to 2005 that suggested an increase in insomnia-related symptoms among the working-age population. The results were based on the National FINRISK (FR) Study samples of the Finnish adult population aged 25-64, and on the Finnish Quality of Work Life Surveys (FQWLS), carried out among Finnish salary earners. Both of these ongoing studies have since provided two new estimates of insomnia-related symptoms. Chronic insomnia-related symptoms were 9.0% (95% CI 8.3-9.7), 9.6% (95% CI 8.8-10.4) in FR 2007 and 2012, respectively; and 9.1% (95% CI 8.3-10.0), 9.2% (95% CI 8.4 10.1) in FQWLS 2008 and 2013, respectively. Occasional insomnia-related symptoms were 45.3% (95% CI 44.1-46.6), 42.5% (95% CI 41.1-43.9) in FR 2007 and 2012, respectively; and 40.3% (95% CI 38.8-41.7), 44.8% (95% CI 41.1-43.9) in FQWLS 2008 and 2013, respectively. The new estimates further strengthen the interpretation of the ongoing increase in occasional insomnia-related symptoms among the Finnish general adult population. The increase in occasional symptoms was most prominent among employees. However, chronic insomnia symptoms showed no further increase. PMID- 26868678 TI - Cardiogenic shock from atypical Takotsubo cardiomyopathy attributed to acute disseminated encephalomyelitis lesion involving the medulla. AB - We present here a case of atypical Takotsubo cardiomyopathy arising as a result of a lesion in the medulla oblongata. The patient was diagnosed with acute disseminated encephalomyelitis, and had improvement with intravenous steroids. PMID- 26868679 TI - Intracerebral haemorrhage: Prognostic scales versus clinical judgment in ICH. PMID- 26868681 TI - Predictors of attendance at specialized survivor clinics in a population-based cohort of adult survivors of childhood cancer. AB - PURPOSE: The purpose of the present study is to determine predictors of attendance at a network of publicly funded specialized survivor clinics by a population-based cohort of adult survivors of childhood cancer. METHODS: We conducted a retrospective study linking data on eligible patients identified in a provincial pediatric cancer registry with health administrative databases to determine attendance at five specialized survivor clinics in the Canadian province of Ontario between 1999 and 2012. Eligible survivors were treated for cancer at <=18 years between 1986 and 2005, had survived >=5 years from their most recent pediatric cancer event, and contributed >=1 year of follow-up after age 18 years. We assessed the impact of cancer type, treatment intensity, cumulative chemotherapy doses, radiation, socioeconomic status, distance to nearest clinic, and care from a primary care physician (PCP) on attendance using recurrent event multivariable regression. RESULTS: Of 7482 children and adolescents treated for cancer over the study period, 3972 were eligible for study inclusion, of which 3912 successfully linked to administrative health data. After a median of 7.8 years (range 0.2-14.0) of follow-up, 1695/3912 (43.3 %) had attended at least one adult survivor clinic visit. Significantly increased rates of attendance were associated with female gender, higher treatment intensity, radiation, higher alkylating agent exposure, higher socioeconomic status, and an annual exam by a PCP. Distance significantly impacted attendance with survivors living >50 km away less likely to attend than those living within 10 km (relative rate 0.77, p = 0.003). CONCLUSION: Despite free access to survivor clinics, the majority of adult survivors of childhood cancer do not attend. IMPLICATIONS FOR CANCER SURVIVORS: Alternate models of care need to be developed and assessed, particularly for survivors living far from a specialized clinic and those at lower risk of developing late effects. PMID- 26868682 TI - Are you a cancer survivor? A review on cancer identity. AB - PURPOSE: Individuals diagnosed with cancer have been shown to interpret the term "cancer survivor" differently and this may have implications for how they cope with their illness. This article reviews the empirical research conducted in the field and aims to formulate recommendations for future research. METHODS: A literature search was conducted on PubMed, PsycInfo, Embase and CINAHL using search strategies customized for each database: standardized subject terms and a wide range of free-text terms for "cancer", "survivor", and "identity". Data from 23 eligible papers were extracted and summarized. RESULTS: Analysis of the studies revealed that individuals diagnosed with cancer could be categorized into five groups based on their attitudes towards being a cancer survivor: embracing, constructive, ambiguous, resisting and non-salient. Identification as "cancer survivor" was found to be highly prevalent within the breast cancer community (77.9 %) and least among individuals diagnosed with prostate cancer (30.6 %). Self-identifying as a cancer survivor was related to better quality of life and mental wellbeing, with those having a childhood diagnosis more likely to transition successfully into adult care. CONCLUSIONS: The findings show that, for a substantial group of individuals, "cancer survivor" is not a title earned upon receiving a cancer diagnosis or completion of treatment, but an identity that may be embraced in time after deliberation. Future studies should examine the endorsement rate in less common cancers and whether choice of cancer identity varies over time. IMPLICATIONS FOR CANCER SURVIVORS: Researchers and healthcare professionals should use caution when using the term "cancer survivor" so as not to alienate anyone who has been diagnosed with cancer but does not identify with it. PMID- 26868684 TI - Potent P2Y12 Inhibitors in Low-Risk Patients: Is There a Medical Need? PMID- 26868680 TI - Maladaptive plasticity in tinnitus--triggers, mechanisms and treatment. AB - Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state could be involved in the development and maintenance of tinnitus via top-down mechanisms. Thus, military personnel in combat are particularly at risk owing to combined risk factors (hearing loss, somatosensory system disturbances and emotional stress). Animal model studies have identified tinnitus-associated neural changes that commence at the cochlear nucleus and extend to the auditory cortex and other brain regions. Maladaptive neural plasticity seems to underlie these changes: it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures, possibly generating the phantom percept. This Review highlights the links between animal and human studies, and discusses several therapeutic approaches that have been developed to target the neuroplastic changes underlying tinnitus. PMID- 26868683 TI - Effects of Ticagrelor Versus Clopidogrel in Troponin-Negative Patients With Low Risk ACS Undergoing Ad Hoc PCI. AB - BACKGROUND: Many low-risk acute coronary syndrome (ACS) patients are not pre treated with a P2Y12 receptor inhibitor, and percutaneous coronary interventions (PCIs) are often performed on an ad hoc basis in this population. Pharmacodynamic (PD) studies comparing ticagrelor versus clopidogrel in patients undergoing ad hoc PCI are lacking. OBJECTIVES: This study sought to assess PD effects of ticagrelor versus clopidogrel loading dose (LD) in the peri-procedural period among troponin-negative ACS patients undergoing ad hoc PCI. METHODS: This was a prospective, open-label, randomized, multicenter, parallel-group, phase IV PD study. One hundred P2Y12 inhibitor-naive patients presenting with biomarker negative ACS and undergoing ad hoc PCI, on a background of aspirin therapy, were randomized to receive either ticagrelor 180 mg LD or clopidogrel 600 mg LD. Platelet reactivity (P2Y12 reaction units [PRU]; VerifyNow assay) was measured at 5 time points: pre-LD, at 0.5, 2, and 8 h post-LD, and at end of PCI. The primary endpoint was PRU levels 2 h post-LD; secondary endpoints included PRU levels at all other time points and inhibition of platelet aggregation; an exploratory analysis evaluated rates of high on-treatment platelet reactivity (HPR) (PRU >208). RESULTS: At 2 h, PRU levels were significantly lower with ticagrelor versus clopidogrel (98.4 +/- 95.4 vs. 257.5 +/- 74.5; p < 0.001; primary endpoint). PRU levels diverged as early as 0.5 h post-LD, with significant differences observed by the end of PCI (mean 0.6 h post-LD) and maintained up to 8 h post-LD. HPR rates were also significantly reduced with ticagrelor compared with clopidogrel at the end of PCI (p = 0.030), and at 2 h (p < 0.001) and 8 h (p < 0.001) after LD. CONCLUSIONS: In low-risk ACS patients undergoing ad hoc PCI, ticagrelor LD provides more prompt and potent platelet inhibition, and lower HPR rates, compared with clopidogrel LD. (Ad Hoc Percutaneous Coronary Intervention Study in Acute Coronary Syndrome Patients: NCT01603082). PMID- 26868685 TI - Nonsyndromic Thoracic Aortic Aneurysm and Dissection: Outcomes With Marfan Syndrome Versus Bicuspid Aortic Valve Aneurysm. AB - BACKGROUND: Genetic aortopathy (GA) underlies thoracic aortic aneurysms (TAA) in younger adults. Comparative survival and predictors of outcomes in nonsyndromic TAA (NS-TAA) are incompletely defined compared to Marfan syndrome (MFS) and bicuspid aortic valve (BAV). OBJECTIVES: The study sought to compare survival and clinical outcomes for individuals with NS-TAA, MFS, and BAV. METHODS: From 1988 to 2014, all patients presenting with GA 16 to 60 years of age were enrolled in a prospective study of clinical outcomes. Risk factors for death and aortic dissection were identified by Cox proportional hazards modeling and a mortality risk score developed. RESULTS: Diagnosis of GA was made for 760 patients (age 36.9 +/- 13.6 years, 26.8% female; NS-TAA, n = 311; MFS, n = 221; BAV, n = 228). MFS patients were younger than NS-TAA and BAV. Presentation with aortic dissection was more common for NS-TAA than MFS or BAV. The 687 patients surviving >30 days after presentation were followed for a median of 7 years. Calculated 10 year mortality was 7.8% for NS-TAA, 8.7% for MFS, and 3.5% for BAV (NS-TAA and MFS vs. BAV p <0.05). Factors associated with all-cause mortality were MFS (p = 0.04), age at presentation, and family history of dissection. CONCLUSIONS: Clinical outcomes for MFS and NS-TAA are similar but worse than BAV. Independent predictors of mortality, including family history of aortic dissection and age, can be included in an Aortopathy Mortality Risk Score to predict survival. Management of NS-TAA, including surgical intervention, should be similar to that of MFS. PMID- 26868686 TI - Familial Nonsyndromic Thoracic Aortic Aneurysms: Unraveling the Mystery and Defining Long-Term Outcome. PMID- 26868688 TI - Reducing Cardiovascular Risk With Ankle Brachial Index Screening: New Evidence for an Old Question? PMID- 26868687 TI - Statins for Prevention of Cardiovascular Events in a Low-Risk Population With Low Ankle Brachial Index. AB - BACKGROUND: Evidence is lacking about the effectiveness of risk reduction interventions in patients with asymptomatic peripheral arterial disease. OBJECTIVES: This study aimed to assess whether statin therapy was associated with a reduction in major adverse cardiovascular events (MACE) and mortality in this population. METHODS: Data were obtained from 2006 through 2013 from the Catalan primary care system's clinical records database (SIDIAP). Patients age 35 to 85 years with an ankle-brachial index <=0.95 and without clinically recognized cardiovascular disease (CVD) were included. Participants were categorized as statins nonusers or new-users (first prescription or represcribed after at least 6 months) and matched 1:1 by inclusion date and propensity score for statin treatment. Conditional Cox proportional hazards modeling was used to compare the groups for the incidence of MACE (myocardial infarction, cardiac revascularization, and ischemic stroke) and all-cause mortality. RESULTS: The matched-pair cohort included 5,480 patients (mean age 67 years; 44% women) treated/nontreated with statins. The 10-year coronary heart disease risk was low (median: 6.9%). Median follow-up was 3.6 years. Incidence of MACE was 19.7 and 24.7 events per 1,000 person-years in statin new-users and nonusers, respectively. Total mortality rates also differed: 24.8 versus 30.3 per 1,000 person-years, respectively. Hazards ratios were 0.80 for MACE and 0.81 for overall mortality. The 1-year number needed to treat was 200 for MACE and 239 for all-cause mortality. CONCLUSIONS: Statin therapy was associated with a reduction in MACE and all-cause mortality among participants without clinical CVD but with asymptomatic peripheral arterial disease, regardless of its low CVD risk. The absolute reduction was comparable to that achieved in secondary prevention. PMID- 26868689 TI - Incidence, Timing, and Predictors of Valve Hemodynamic Deterioration After Transcatheter Aortic Valve Replacement: Multicenter Registry. AB - BACKGROUND: Scarce data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) after transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study sought to determine the incidence, timing, and predictors of VHD in a large cohort of patients undergoing TAVR. METHODS: This multicenter registry included 1,521 patients (48% male; 80 +/- 7 years of age) who underwent TAVR. Mean echocardiographic follow-up was 20 +/- 13 months (minimum: 6 months). Echocardiographic examinations were performed at discharge, at 6 to 12 months, and yearly thereafter. Annualized changes in mean gradient (mm Hg/year) were calculated by dividing the difference between the mean gradient at last follow-up and the gradient at discharge by the time between examinations. VHD was defined as a >=10 mm Hg increase in transprosthetic mean gradient during follow-up compared with discharge assessment. RESULTS: The overall mean annualized rate of transprosthetic gradient progression during follow-up was 0.30 +/- 4.99 mm Hg/year. A total of 68 patients met criteria of VHD (incidence: 4.5% during follow-up). The absence of anticoagulation therapy at hospital discharge (p = 0.002), a valve-in-valve (TAVR in a surgical valve) procedure (p = 0.032), the use of a 23-mm valve (p = 0.016), and a greater body mass index (p = 0.001) were independent predictors of VHD. CONCLUSIONS: There was a mild but significant increase in transvalvular gradients over time after TAVR. The lack of anticoagulation therapy, a valve-in-valve procedure, a greater body mass index, and the use of a 23-mm transcatheter valve were associated with higher rates of VHD post-TAVR. Further prospective studies are required to determine whether a specific antithrombotic therapy post-TAVR may reduce the risk of VHD. PMID- 26868690 TI - Shedding More Light on Valve Thrombosis After Transcatheter Aortic Valve Replacement. PMID- 26868691 TI - Contributions of Nondiastolic Factors to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction. AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined. OBJECTIVES: The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF. METHODS: We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 +/- 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction). RESULTS: Symptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e'] <13 both at rest and exercise; n = 63), C2 (E/e' >13 only at exercise; n = 118), and C3 (E/e' >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e' (-0.6 +/- 1.7 vs. 3.7 +/- 2.8; p < 0.0001), global longitudinal strain (2.9 +/- 2.0 vs. 1.6 +/- 2.8; p < 0.002), VAC (-0.21 +/- 0.17 vs. -0.09 +/- 0.15; p < 0.0001), and in VO2-HR gradient (0.30 +/- 0.07 vs. 0.26 +/- 0.11; p < 0.01) were significantly different in stages B and C. CONCLUSIONS: Normal E/e' response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF. PMID- 26868692 TI - Is HFpEF One Disease or Many? PMID- 26868694 TI - Ventricular Tachycardia Ablation: Are We Winning the Battle But Losing the War? PMID- 26868693 TI - Long-Term Success of Irrigated Radiofrequency Catheter Ablation of Sustained Ventricular Tachycardia: Post-Approval THERMOCOOL VT Trial. AB - BACKGROUND: Radiofrequency catheter ablation is used to treat recurrent ventricular tachycardia (VT). OBJECTIVES: This study evaluated long-term safety and effectiveness of radiofrequency catheter ablation using an open-irrigated catheter. METHODS: Patients with sustained monomorphic ventricular tachycardia associated with coronary disease were analyzed for cardiovascular-specific adverse events within 7 days of treatment, hospitalization duration, 6-month sustained monomorphic ventricular tachycardia recurrence, quality of life measured by the Hospital Anxiety and Depression Scale, long-term (1-, 2-, and 3 year) survival, symptomatic VT control, and amiodarone use. RESULTS: Overall, 249 patients, mean age 67.4 years, were enrolled. The cardiovascular-specific adverse events rate was 3.9% (9 of 233) with no strokes. Noninducibility of targeted VT was achieved in 75.9% of patients. Post-ablation median hospitalization was 2 days. At 6 months, 62.0% (114 of 184) of patients had no sustained monomorphic ventricular tachycardia recurrence; the proportion of patients with implantable cardioverter-defibrillator shocks decreased from 81.2% to 26.8% (p < 0.0001); the frequency of VT in implantable cardioverter-defibrillator patients with recurrences was reduced by >=50% in 63.8% of patients; and the proportion with normal Hospital Anxiety and Depression Scale scores increased from 48.8% to 69.1% (p < 0.001). Patient-reported VT remained steady for 1, 2, and 3 years at 22.7%, 29.8%, and 24.1%, respectively. Amiodarone use and hospitalization decreased from 55% and 77.2% pre-ablation to 23.3% and 30.7%, 18.5% and 36.7%, 17.7% and 31.3% at 1, 2, and 3 years, respectively. CONCLUSIONS: Radiofrequency catheter ablation reduced implantable cardioverter-defibrillator shocks and VT episodes and improved quality of life at 6 months. A steady 3-year nonrecurrence rate with reduced amiodarone use and hospitalizations indicate improved long-term outcomes. (NaviStar ThermoCool Catheter for Endocardial RF Ablation in Patients With Ventricular Tachycardia [THERMOCOOL VT]; NCT00412607). PMID- 26868695 TI - Editor-in-Chief's Top Picks From 2015: Part One. AB - Each week, I record audio summaries for every article in JACC, as well as an issue summary. While this process has been time-consuming, I have become very familiar with every paper that we publish. Thus, I have personally selected the papers (both original investigations and review articles) from 13 distinct specialties for your review. In addition to my personal choices, I have included manuscripts that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. There are approximately 130 articles selected across this 2-part series, which represent less than 3% of the papers submitted to the Journal in 2015. In order to present the full breadth of this important research in a consumable fashion, we will present these manuscripts over the course of 2 issues in JACC. Part One includes the sections: Congenital Heart Disease, Coronary Disease & Interventions, CVD Prevention & Health Promotion, Cardiac Failure, Cardiomyopathies, Genetics, Omics, & Tissue Regeneration, and Hypertension (1-60). Part Two includes the sections: Imaging, Metabolic Disorders & Lipids, Rhythm Disorders, Statistics, Valvular Heart Disease, and Vascular Medicine. PMID- 26868696 TI - A Test in Context: High-Sensitivity C-Reactive Protein. AB - The inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) adds prognostic information on cardiovascular risk comparable to blood pressure or cholesterol. Values <1, 1 to 3, and >3 mg/l indicate lower, average, or higher relative cardiovascular risk, respectively. Global risk algorithms that include hsCRP outperform those solely using Framingham covariates. Although diet, exercise, and smoking cessation are first steps for patients with a proinflammatory response, JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial data demonstrate that statins reduce by 47% the rate of first myocardial infarction, stroke, or confirmed cardiovascular death when given to patients with low-density lipoprotein-C levels of <130 mg/dl and hsCRP of >2 mg/l (hazard ratio: 0.53; 95% confidence interval: 0.40 to 0.69; p < 0.00001). In current U.S. guidelines, hsCRP carries a class IIb assessment and is most appropriate in primary prevention when clinical decisions to initiate statin therapy are uncertain. Ongoing multinational trials are pursuing whether reducing inflammation will decrease vascular event rates. PMID- 26868697 TI - U.S. Trends in Inpatient Utilization of Fractional Flow Reserve and Percutaneous Coronary Intervention. PMID- 26868698 TI - Comparison of the American PPCM Registry Data With International Registries. PMID- 26868699 TI - Reply: Comparison of the American PPCM Registry Data With International Registries. PMID- 26868700 TI - Final Common Pathway of Aortic Dilation?: Heterogeneity of Aortic Wall Property Causes the Aneurysmal Change. PMID- 26868701 TI - Reply: Final Common Pathway of Aortic Dilation?: Heterogeneity of Aortic Wall Property Causes the Aneurysmal Change. PMID- 26868702 TI - Comparison between PCR and larvae visualization methods for diagnosis of Strongyloides stercoralis out of endemic area: A proposed algorithm. AB - Underdiagnosis of chronic infection with the nematode Strongyloides stercoralis may lead to severe disease in the immunosuppressed. Thus, we have set-up a specific and highly sensitive molecular diagnosis in stool samples. Here, we compared the accuracy of our polymerase chain reaction (PCR)-based method with that of conventional diagnostic methods for chronic infection. We also analyzed clinical and epidemiological predictors of infection to propose an algorithm for the diagnosis of strongyloidiasis useful for the clinician. Molecular and gold standard methods were performed to evaluate a cohort of 237 individuals recruited in Buenos Aires, Argentina. Subjects were assigned according to their immunological status, eosinophilia and/or history of residence in endemic areas. Diagnosis of strongyloidiasis by PCR on the first stool sample was achieved in 71/237 (29.9%) individuals whereas only 35/237(27.4%) were positive by conventional methods, requiring up to four serial stool samples at weekly intervals. Eosinophilia and history of residence in endemic areas have been revealed as independent factors as they increase the likelihood of detecting the parasite according to our study population. Our results underscore the usefulness of robust molecular tools aimed to diagnose chronic S. stercoralis infection. Evidence also highlights the need to survey patients with eosinophilia even when history of an endemic area is absent. PMID- 26868703 TI - Radiological input during paediatric multidisciplinary team meetings and its influence on clinical patient management. AB - INTRODUCTION: There is little information about the role of the radiologist at multidisciplinary team meetings; in particular their influence on patient management. To evaluate the influence of radiologists on clinical patient management during multidisciplinary meetings. METHODS: Prospective data were collected over a 5-week period from multidisciplinary team meetings across four paediatric clinical domains. Radiological input was recorded for each case discussion, including the type of influence and its potential effect on clinical patient management. RESULTS: One hundred and forty paediatric cases were reviewed. Radiological advice was requested from the radiologist for 25.7% (N = 36) of cases. In 17.9% (N = 25) this advice was judged to have influenced clinical patient management. There were two cases where new imaging findings were discovered. CONCLUSIONS: Radiologists influence clinical patient management during multidisciplinary team meetings primarily by providing differential diagnoses and guidance regarding future imaging, with respect to both the necessity and the modality. Occasionally, when imaging is reviewed at these meetings, new findings are discovered that impact on patient management. PMID- 26868704 TI - Analysis of dopamine beta hydroxylase gene polymorphisms in migraine. AB - BACKGROUND: Migraine is a complex neurological disorder characterized by severe recurrent headache, nausea, vomiting, photophobia, and phonophobia. The frequency and duration of these symptoms varies among individuals. Dopaminergic systems are believed to be involved in migraine pathophysiology. We aimed to look for association of polymorphisms in dopaminergic genes in genetic susceptibility to migraine in Turkey population. METHODS: The present study was designed to explore possible association of three polymorphisms, (1021C>T (Rs1611115), +1603C>T (Rs6271; C535R) and +444G>A (rs1108580), of Dopamin Beta Hydroxylase gene in migraine patients. 200 migraine patients and 267 healthy controls were included in the study. Genomic DNA was extracted from blood and genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism methods (PCR-RFLP). RESULTS: Statistical evaluation of data results showed a significant association for allelic and genotypic frequency distribution between the Dopamin Beta Hydroxylase gene +1603C>T polymorphism and migraine (p=0.000, OR: 4.36, 95% CI: 2.73-7.16). There was no association observed between the -1021C>T and +444 G>A polymorphisms of the Dopamin Beta Hydroxylase gene and migraine (p=0.8731 and p=0.7584). CONCLUSIONS: This study reflects that Dopamin Beta Hydroxylase gene +1603C>T polymorphism may be one of the many genetic factors for migraine susceptibility in the Turkish population. PMID- 26868706 TI - Species and Size Composition of Seahorses (Genus Hippocampus, Family Syngnathidae) in the Coastal Waters and Local Market of Kota Kinabalu, Sabah, Malaysia. AB - Seahorse diversity (genus Hippocampus, Family Syngnathidae), species identification, size composition and sexual dimorphism were studied from November 2012 to March 2013 in selected coastal waters around Kota Kinabalu, Sabah and the local market trade. Six species of seahorses were identified in the study: (1) Hippocampus barbouri, (2) Hippocampus comes, (3) Hippocampus kelloggi, (4) Hippocampus kuda, (5) Hippocampus spinosissimus and (6) Hippocampus trimaculatus. All six species were sold at the local market, and the dried seahorses were obtained mainly by local fishermen using trawl by-catch method and traded as traditional medicine, souvenirs and other uses. Four species were identified by direct samplings in various different habitats of Kota Kinabalu coastal waters: (1) H. barbouri, (2) H. comes, (3) H. kuda, and (4) H. spinosissimus. Based on the results, H. comes was the largest in size among the four fresh/live species found (mean standard length [SL]: 148.25+/-1.26 mm), whereas H. barbouri was the smallest species (mean SL: 129+/-7.81 mm). For the dried samples, H. kelloggi was the largest (mean SL: 245.25+/-14.55 mm) and H. barbouri was the smallest (mean SL: 127.21+/-10.01 mm). No significant difference (p>0.05) was observed between the lengths of males and females in every seahorse species, and there was no sexual size dimorphism in any of the species. The findings from the study are significant to provide baseline data for the conservation efforts of these unique marine teleost. PMID- 26868705 TI - Visual recovery after retinal detachment with macula-off: is surgery within the first 72 h better than after? AB - AIMS: To investigate the influence of lag time between the onset of central visual acuity loss and surgical intervention of macula-off retinal detachment. METHODS: This retrospective case series examined all consecutively treated eyes with primary macula-off retinal detachment at the University Hospital Hamburg (Germany) from February 2010 to February 2015. Records of 1727 patients operated by six surgeons were reviewed. Eighty-nine eyes (5.2%) from 89 patients met the inclusion and exclusion criteria. The main outcome measure studied was final visual acuity as a function of symptom duration of macula-off detachment. Secondary outcome measures studied were influence of age and surgical technique. Symptom duration was defined as the time from the onset of loss of central vision to surgical intervention. RESULTS: After 10 days no clinically relevant difference was seen in final visual acuity. Eyes with symptom duration of 3 days or less achieved best final visual acuity (p<0.001). Age and preoperative visual acuity had no influence while vitrectomised eyes had better outcome compared with those with scleral buckling. CONCLUSIONS: Our study suggests that 1. After 10 days of central visual acuity loss, the final visual outcome is clinically comparable and independent of further delay of surgery up to 30 days. 2. Eyes treated up to 3 days after onset of loss of central vision have better final visual acuity than eyes with longer lag time. However, we did not find statistically significant differences within the first 3 days. 3. Surgery for macula-off retinal detachment may therefore most likely not be postponed without compromising the patient's visual prognosis. PMID- 26868708 TI - Range Measurement and a Habitat Suitability Map for the Norway Rat in a Highly Developed Urban Environment. AB - Studies of habitat suitability (HS) are essential when animals' habitats have been altered or when animals migrate to a habitat different from their natural habitat. This study assessed HS and used an integrated geographic information system in the assessment of Rattus norvegicus in a highly developed urban environment. Using data from the Campbell market and the police quarters of George Town, Malaysia, home range (through the use of 100% Minimum Convex Polygon [MCP], 95% MCP and 95% Harmonic Mean [HM]) was estimated. Home range for male rats at Campbell market reached an asymptote, with a slight increase, at 96 radio fixes (home range = 133.52 m(2); core area = 29.39 m(2)). Female rats reached an asymptote at 62 radio fixes (home range = 13.38 m(2); core area = 9.17 m(2)). At Campbell market, male rats emerged at 1900 hours every day, whereas females emerged at 2000 hours; at police quarters, the most common time of emergence for males was 2000 hours and for females was 2200. Raster charts of R. norvegicus showed that rat hot spots can be grouped into 4 zones (market, shop houses, settlement and general places). The standardised raster chart isolated the market as the major rallying points of the rats (hot spots) by producing the highest rats frequencies of 255. All of the habitat suitability thresholds, including the built-up points, skip bins, water source and nature of the site explored in this study, produced a structural pattern (monotonic increase or decrease) of habitat suitability. PMID- 26868707 TI - Larvicidal and Histopathological Effects of Cassia siamea Leaf Extract against Culex quinquefasciatus. AB - A traditional Thai medicinal extract from Cassia siamea was evaluated with respect to its larvicidal properties by determining the median lethal concentration (LC50) at 24, 48, 72 and 96 h against the fourth instar larvae of Culex quinquefasciatus, which is a carrier of mosquito-borne diseases, by studying the histopathological alterations. The 24, 48, 72 and 96 h LC50 values were 394.29, 350.24, 319.17 and 272.42 ppm, respectively. The histopathological lesions after exposure to 25% of the 24-h LC50 were observed primarily in the midgut of the larva. Lesions with edema, swelling, and deformation or elongation of the epithelial cells were observed. Moreover, cells protruding into the lumen and absent microvilli were also found in some areas. The present study reveals that aqueous C. siamea leaf extracts have natural biopesticide properties. PMID- 26868709 TI - Mating Compatibility and Restriction Analysis of Ganoderma Isolates from Oil Palm and Other Palm Hosts. AB - Mating compatibility and restriction analyses of Internal Transcribed Spacer (ITS) regions were performed to determine the relations between Ganoderma boninense, the most common species associated with basal stem rot in oil palm and Ganoderma isolates from infected oil palm, two ornamental palms, sealing wax palm (Cyrtostachys renda) and MacArthur palm (Ptychosperma macarthurii), an isolate from coconut stump (Cocos nucifera), Ganoderma miniatocinctum, Ganoderma zonatum and Ganoderma tornatum. The results showed that G. boninense was compatible with Ganoderma isolates from oil palm, G. miniatocinctum and G. zonatum, Ganoderma isolates from sealing wax palm, MacArthur palm and coconut stump. G. boninense was not compatible with G. tornatum. Therefore, the results suggested that the G. boninense, G. miniatocinctum, G. zonatum, and Ganoderma isolates from oil palm, ornamental palms and coconut stump could represent the same biological species. In performing a restriction analysis of the ITS regions, variations were observed in which five haplotypes were generated from the restriction patterns. An unweighted pair-group method with arithmetic averages (UPGMA) cluster analysis showed that all the Ganoderma isolates were grouped into five primary groups, and the similarity values of the isolates ranged from 97% to 100%. Thus, a restriction analysis of the ITS regions showed that G. boninense and the Ganoderma isolates from other palm hosts were closely related. On the basis of the mating compatibility test and the restriction analysis of the ITS regions performed in this study, a diverse group of Ganoderma species from oil palm and other palm hosts are closely related, except for G. tornatum and Ganoderma isolates from tea and rubber. PMID- 26868710 TI - Reproductive Cycle of Hard Clam, Meretrix lyrata Sowerby, 1851 (Bivalvia: Veneridae) from Sarawak, Malaysia. AB - A study of the reproductive cycle of the hard clam, Meretrix lyrata, was documented based on histological observation and Gonad Index (GI). Samples were taken from estuarine waters of the Buntal River in Sarawak, Malaysia. The gonad of M. lyrata started to develop in September 2013. Gametogenesis continued to develop until the maturation and spawning stage from February to April 2014. The GI pattern for a one-year cycle showed a significant correlation with chlorophyll a. The corresponding GI with chlorophyll a suggested that the development of the reproductive cycle of M. lyrata required a high amount of food to increase gametogenesis. PMID- 26868711 TI - Efficacy of Insecticide and Bioinsecticide Ground Sprays to Control Metisa plana Walker (Lepidoptera: Psychidae) in Oil Palm Plantations, Malaysia. AB - The effectiveness of the synthetic insecticides trichlorfon, lambda-cyhalothrin, cypermethrin emulsion concentrated (EC) and cypermethrin emulsion water based (EW) and a bio-insecticide, Bacillus thuringiensis subsp. kurstaki (Btk), was evaluated at 3, 7, 14 and 30 days after treatment (DAT) for the control of Metisa plana larvae in an oil palm (Elaeis guineensis) plantation in Malaysia. Although all synthetic insecticides effectively reduced the larval population of M. plana, trichlorfon, lambda-cyhalothrin and cypermethrin EC were the fastest-acting. The larval population dropped below the economic threshold level (ETL) 30 days after a single application of the synthetic insecticides. Application of Btk, however, gave poor results, with the larval population remaining above the ETL post treatment. In terms of operational productivity, ground spraying using power spray equipment was time-consuming and resulted in poor coverage. Power spraying may not be appropriate for controlling M. plana infestations in large fields. Using a power sprayer, one man could cover 2-3 ha per day. Hence, power spraying is recommended during outbreaks of infestation in areas smaller than 50 ha. PMID- 26868712 TI - Bird Diversity and Structure in Different Land-use Types in Lowland South-Central Mindanao, Philippines. AB - Birds are crucial to maintaining the balance of many ecosystems by providing various ecological services. The diversity of birds and their feeding guilds in different land-use types were investigated in south-central Mindanao to elucidate the effect of disturbance and habitat modification on bird communities. Point count method was employed to identify birds in three habitat types: i) agroforests; ii) ricefields; iii) roads and heavily disturbed areas. A total of 1114 bird sightings were recorded that included 33 species of 24 families; of these, 3 were Philippine endemics, and 5 were migrant species. Among all of the habitat types, the highest species diversity was found in agroforests (1/D = 16.148), and the lowest was recorded from roads and heavily disturbed habitats. The species composition of agroforests was more similar to ricefields than to areas with high levels of disturbance, such as roads. The characteristic of the vegetation and the availability of food resources may be vital to the diversity of birds in every habitat as evidenced by the high species richness of frugivores and insectivores in agroforests and ricefields, respectively, where food source is largely available. The observation of Streptopelia tranquebarica was a new record for Mindanao, and it was particularly sighted in ricefields. Therefore, this study indicates that land-use change and modification may alter bird diversity structure, and the maintenance of the vegetation in land-use types as food and resource, and as habitat is essential to the conservation of the native and ecologically-important bird species in south-central Mindanao. PMID- 26868713 TI - First Record of Hippa adactyla (Fabricius, 1787; Crustacea, Anomura, Hippidae) from Indonesian Waters. AB - Specimens of Hippa adactyla (Crustacea, Anomura, Hippidae) were collected from several coasts of Indonesia (Sumatera, Java, Bali-Lombok and Sulawesi). This finding represents the first record of this species in Indonesia and confirms its presence in the Indian Ocean and in the Wallacea region. Its systematic and morphological characteristics are described, and its distribution in Indonesia is presented. One of the main characteristics of this species is a median lobe in the anterior part of the carapace, which has 3-4 lobes. Likewise, the left antenna has 2-6 articles. PMID- 26868714 TI - Contribution to the Pteridophyte Flora of Langkawi Archipelago, Peninsular Malaysia. AB - The pteridophyte flora of Langkawi Archipelago consists of 130 species, 1 subspecies and 12 varieties in 68 genera and 27 families. This value represents 22.1% of the 647 taxa at the species level and below reported for Peninsular Malaysia. Of the 143 recorded taxa of pteridophytes at the species level and below, 8 species in 2 genera and 2 families are lycophytes and the other 135 taxa in 66 genera and 25 families are monilophytes or ferns. PMID- 26868715 TI - Screening for Zoonotic Fascioliasis in Slaughtered Large Ruminants in Abattoirs in Perak, Malaysia. AB - Fascioliasis, or trematode infestation, is an important disease caused by Fasciola hepatica and Fasciola gigantica. Both species are hepatic parasites that affect humans. We have examined the zoonotic aspects of fascioliasis. A total of 80 fresh liver samples were collected from 67 Kedah-Kelantan crossbred cattle and 13 Murrah buffalo at 4 local abattoirs in Perak, Malaysia. The samples were examined macroscopically to detect the presence of Fasciola spp. The results show 7.50% (6 of 80) of the animals were diagnosed with fascioliasis. Overall, 7.46% (5 of 67) and 7.69% (1 of 13) of cattle and buffalo samples were positive, respectively. There were only F. gigantica species identified in the samples. Our findings suggest that precautions should be taken because the disease has a zoonotic impact on public health. PMID- 26868716 TI - Upregulated CCL28 expression in the nasal mucosa in experimental allergic rhinitis: Implication for CD4(+) memory T cell recruitment. AB - During nasal immune responses, lymphocytes activated in the nasopharynx associated lymphoid tissue (NALT) are thought to traffic to the nasal mucosa. Here we found a prominent infiltration of CD4(+) memory T cells into the nasal mucosa in a mouse model of allergic rhinitis. CCR3 and CCR10 mRNA was increased in the NALT, and CCR3- or CCR10-expressing CD4(+) T cells were present in the nasal mucosa. CCL28, a chemokine ligand for CCR3 and CCR10, was upregulated in nasal epithelial cells. Our results suggest that memory CD4(+) T cells traffic to the nasal mucosa in a process that may involve CCL28 and its receptors CCR3 and CCR10. PMID- 26868717 TI - The relevance of membrane models to understand nanoparticles-cell membrane interactions. AB - Over the past two decades, numerous types of nanoparticles (NPs) have been developed for medical applications; however only a few nanomedicines are actually available on the market. One reason is the lack of understanding and data concerning the NP fate and their behavior upon contact with biological media and cell membranes. Biomimetic membrane models are interesting tools to approach and understand NPs-cell membrane interactions. The use of these models permits one to control physical and chemical parameters and to rapidly compare membrane types and the influence of different media conditions. The interactions between NPs and cell membranes can be qualified and quantified using analytical and modeling methods. In this review, the major studies concerning NPs-cell membrane models and associated methods are described. The advantages and drawbacks for each method are compared for the different models. The key mechanisms of interactions between NPs and cell membranes are revealed using cell membrane models and are interrogated in comparison with the NP behavior in cellulo or in vivo. Investigating the interactions between NPs and cell membrane models is now proposed as an intermediate step between physicochemical characterization of NPs and biological assays. PMID- 26868718 TI - The Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 employs a new glycoside hydrolase family 70 4,6-alpha-glucanotransferase enzyme (GtfD) to synthesize a reuteran like polymer from maltodextrins and starch. AB - BACKGROUND: Originally the glycoside hydrolase (GH) family 70 only comprised glucansucrases of lactic acid bacteria which synthesize alpha-glucan polymers from sucrose. Recently we have identified 2 novel subfamilies of GH70 enzymes represented by the Lactobacillus reuteri 121 GtfB and the Exiguobacterium sibiricum 255-15 GtfC enzymes. Both enzymes catalyze the cleavage of (alpha1->4) linkages in maltodextrin/starch and the synthesis of consecutive (alpha1->6) linkages. Here we describe a novel GH70 enzyme from the nitrogen-fixing Gram negative bacterium Azotobacter chroococcum, designated as GtfD. METHODS: The purified recombinant GtfD enzyme was biochemically characterized using the amylose-staining assay and its products were identified using profiling chromatographic techniques (TLC and HPAEC-PAD). Glucans produced by the GtfD enzyme were analyzed by HPSEC-MALLS-RI, methylation analysis, 1D/2D [1]H/[13]C NMR spectroscopy and enzymatic degradation studies. RESULTS: The A. chroococcum GtfD is closely related to GtfC enzymes, sharing the same non-permuted domain organization also found in GH13 enzymes and displaying 4,6-alpha glucanotransferase activity. However, the GtfD enzyme is unable to synthesize consecutive (alpha1->6) glucosidic bonds. Instead, it forms a high molecular mass and branched alpha-glucan with alternating (alpha1->4) and (alpha1->6) linkages from amylose/starch, highly similar to the reuteran polymer synthesized by the L. reuteri GtfA glucansucrase from sucrose. CONCLUSIONS: In view of its origin and specificity, the GtfD enzyme represents a unique evolutionary intermediate between family GH13 (alpha-amylase) and GH70 (glucansucrase) enzymes. GENERAL SIGNIFICANCE: This study expands the natural repertoire of starch-converting enzymes providing the first characterization of an enzyme that converts starch into a reuteran-like alpha-glucan polymer, regarded as a health promoting food ingredient. PMID- 26868719 TI - Electron work functions of ferrite and austenite phases in a duplex stainless steel and their adhesive forces with AFM silicon probe. AB - Local electron work function, adhesive force, modulus and deformation of ferrite and austenite phases in a duplex stainless steel were analyzed by scanning force microscopy. It is demonstrated that the austenite has a higher electron work function than the ferrite, corresponding to higher modulus, smaller deformation and larger adhesive force. Relevant first-principles calculations were conducted to elucidate the mechanism behind. It is demonstrated that the difference in the properties between austenite and ferrite is intrinsically related to their electron work functions. PMID- 26868720 TI - Incidence and prevalence of thyroid dysfunction in type 1 diabetes. AB - AIMS: To estimate prevalence and incidence of auto-immune thyroid disease and thyroid auto-antibodies in an unselected cohort of patients with DM1, including stratification by age, gender and duration of diabetes. METHODS: Patients with T1D visiting our outpatient clinic between 1995 and 2011 were included. We calculated the prevalence of AITD at first screening and estimated prevalence and incidence rates during follow-up. RESULTS: A total of 1304 patients were included, 48.9% being female. Mean age of diabetes onset was 18.7 years. Of all patients without known thyroid disorder first screened for AITD, 10.3 % (n=104) was diagnosed with hypo- or hyperthyroidism. The average prevalence of AITD in our population was 112/1000 patients. We found 128 new cases of AITD, 101 cases of hypothyroidism and 27 of hyperthyroidism between 1995 and 2011 with accompanying incidences of 11.2/1000 person-years (95% CI 9.5-13.4), 8.9/1000 person-years (95% CI, 7.3-10.8) and 2.4/1000 person-years (95% CI, 1.6-3.5), respectively. Age-stratified incidence of AITD was comparable at all ages in both males and females, with an approximately two times higher incidence in females. CONCLUSIONS: The incidence of AITD among T1D patients is high, but stable among all ages and independent of diabetes duration. PMID- 26868721 TI - Seasonal life history trade-offs in two leafwing butterflies: Delaying reproductive development increases life expectancy. AB - Surviving inhospitable periods or seasons may greatly affect fitness. Evidence of this exists in the prevalence of dormant stages in the life cycles of most insects. Here I focused on butterflies with distinct seasonal morphological types (not a genetic polymorphism) in which one morphological type, or form, delays reproduction until favorable conditions return, while the other form develops in an environment that favors direct reproduction. For two butterflies, Anaea aidea and A. andria, I tested the hypothesis that the development of each seasonal form involves a differential allocation of resources to survival at eclosion. I assayed differences in adult longevity among summer and winter forms in either a warm, active environment or a cool, calm environment. Winter form adults lived 40 times longer than summer form but only in calm, cool conditions. The magnitude of this difference provided compelling evidence that the winter form body plan and metabolic strategy (i.e. resource conservatism) favor long term survival. This research suggests that winter form adults maintain lowered metabolic rate, a common feature of diapause, to conserve resources and delay senescence while overwintering. PMID- 26868722 TI - Nutrition and dopamine: An intake of tyrosine in royal jelly can affect the brain levels of dopamine in male honeybees (Apis mellifera L.). AB - Precursors of neuroactive substances can be obtained from dietary sources, which can affect the resulting production of such substances in the brain. In social species, an intake of the precursor in food could be controlled by social interactions. To test the effects of dietary tyrosine on the brain dopamine levels in social insect colonies, male and worker honeybees were fed tyrosine or royal jelly under experimental conditions and the brain levels of dopamine and its metabolite were then measured. The results showed that the levels of dopamine and its metabolite in the brains of 4- and 8-day-old workers and 8-day-old males were significantly higher in tyrosine-fed bees than in control bees, but the levels in 4-day-old males were not. The brain levels of dopamine and its metabolite in 4- and 8-day-old males and workers were significantly higher in royal jelly-fed bees than in control bees, except for one group of 4-day-old workers. Food exchanges with workers were observed in males during 1-3 days, but self-feedings were also during 5-7 days. These results suggest that the brain levels of dopamine in males can be controlled by an intake of tyrosine in food via exchanging food with nestmates and by self-feeding. PMID- 26868723 TI - Chill-coma recovery time, age and sex determine lipid profiles in Ceratitis capitata tissues. AB - The remodeling of membrane composition by changes in phospholipid head groups and fatty acids (FA) degree of unsaturation has been associated with the maintenance of membrane homeostasis under stress conditions. Overall lipid levels and the composition of cuticle lipids also influence insect stress resistance and tissue protection. In a previous study, we demonstrated differences in survival, behavior and Cu/Zn superoxide dismutase gene expression between subgroups of Ceratitis capitata flies that had a reversible recovery from chill-coma and those that developed chilling-injury. Here, we analyzed lipid profiles from comparable subgroups of 15 and 30-day-old flies separated according to their recovery time after a chill-coma treatment. Neutral and polar lipid classes of chill-coma subgroups were separated by thin layer chromatography and quantified by densitometry. FA composition of polar lipids of chill-coma subgroups and non stressed flies was evaluated using gas chromatography coupled to mass spectrometry. Higher amounts of neutral lipids such as triglycerides, diacylglycerol, wax esters, sterol esters and free esters were found in male flies that recovered faster from chill-coma compared to slower flies. A multivariate analysis revealed changes in patterns of storage and cuticle lipids among subgroups both in males and females. FA unsaturation increased after cold exposure, and was higher in thorax of slower subgroups compared to faster subgroups. The changes in neutral lipid patterns and FA composition depended on recovery time, sex, age and body-part, and were not specifically associated with the development of chilling-injury. An analysis of phospholipid classes showed that the phosphatidylcholine to lysophosphatidylcholine ratio (PC/LPC) was significantly higher, or showed a tendency, in subgroups that may have developed chilling-injury compared to those with a reversible recovery from coma. PMID- 26868724 TI - Sexual difference in juvenile-hormone titer in workers leads to sex-biased soldier differentiation in termites. AB - In termites, the soldier caste, with its specialized defensive morphology, is one of the most important characteristics for sociality. Most of the basal termite species have both male and female soldiers, and the soldier sex ratio is almost equal or only slightly biased. However, in the apical lineages (especially family Termitidae), there are many species that have soldiers with strongly biased sex ratio. Generally in termites, since high juvenile hormone (JH) titer is required for soldier differentiation from a worker via a presoldier stage, it was hypothesized that the biased soldier-sex ratio was caused by differences in JH sensitivity and/or JH titer between male and female workers. Therefore, we focused on the presoldier differentiation and the worker JH titer in species with only male soldiers (Nasutitermes takasagoensis) and with both male and female soldiers (Reticulitermes speratus) in natural conditions. In the former species, there are four types of workers; male minor, male medium, female medium and female major workers, and presoldiers differentiate from male minor workers. First, we tried to artificially induce presoldiers from male and female workers. In N. takasagoensis, the presoldier differentiation rate and mortality was significantly higher in male minor workers. Morphological analyses showed that both male and female induced presoldiers possessed normal soldier-specific morphologies. It was suggested that female workers, from which soldiers do not differentiate under natural conditions, also maintained the physiological and developmental potential for soldier differentiation. In R. speratus, however, no differences were observed in solder differentiation rate and mortality between male and female workers. Second, the JH titers of each sex/type of workers were quantified by high performance liquid chromatography-mass spectrometry in two different seasons (April and December). The results showed that, in N. takasagoensis, JH titer in male minor workers was consistently higher than those in other worker types. In R. speratus, in contrast, there were no significant differences in JH titers between male and female workers. These results suggested that, in N. takasagoensis, male minor workers maintain JH titers at a high level throughout a year, and this may cause the male-biased presoldier differentiation. PMID- 26868725 TI - Balancing of lipid, protein, and carbohydrate intake in a predatory beetle following hibernation, and consequences for lipid restoration. AB - Carnivorous animals are known to balance their consumption of lipid and protein, and recent studies indicate that some mammalian carnivores also regulate their intake of carbohydrate. We investigated macronutrient balancing and lipid restoration following hibernation in the ground beetle Anchomenus dorsalis, hypothesizing that carbohydrates might be important energy sources upon hibernation when predator lipid stores are exhausted and prey are equally lean. We recorded the consumption of lipid, protein, and carbohydrate over nine days following hibernation, as the beetles foraged to refill their lipid stores. Each beetle was given the opportunity to regulate consumption from two semi-artificial foods differing in the proportion of two of the three macronutrients, while the third macronutrient was kept constant. When analyzing consumption of the three macronutrients on an energetic basis, it became apparent that the beetles regulated lipid and carbohydrate energy interchangeably and balanced the combined energy intake from the two macronutrients against protein intake. Restoration of lipid stores was independent of the availability of any specific macronutrient. However, the energetic consumption required to refill lipid stores was higher when a low proportion of lipids was ingested, suggesting that lipids were readily converted into lipid stores while there were energetic costs associated with converting carbohydrate and protein into stored lipids. Our experiment demonstrates that carbohydrates are consumed and regulated as a non-protein energy source by A. dorsalis despite an expectedly low occurrence of carbohydrates in their natural diet. Perhaps carbohydrates are in fact an overlooked supplementary energy source in the diet of carnivorous arthropods. PMID- 26868726 TI - Successful rapid desensitization to temozolomide: A case series. PMID- 26868727 TI - Practice Variation in Management of Childhood Asthma Is Associated with Outcome Differences. AB - BACKGROUND: Although specialist asthma care improves children's asthma outcomes, the impact of primary care management is unknown. OBJECTIVE: To determine whether variation in preventive and acute care for asthma in pediatric practices affects patients' outcomes. METHODS: For 22 practices, we aggregated 12-month patient data obtained by chart review and parent telephone interviews for 948 children, 3 to 12 years old, diagnosed with asthma to obtain practice-level measures of preventive (>=1 asthma maintenance visit/year) and acute (>=1 acute asthma visit/year) asthma care. Relationships between practice-level measures and individual asthma outcomes (symptom-free days, parental quality of life, emergency department [ED] visits, and hospitalizations) were explored using generalized estimating equations, adjusting for seasonality, specialist care, Medicaid insurance, single-family status, and race. RESULTS: For every 10% increase in the proportion of children in the practice receiving preventive care, symptom-free days per child increased by 7.6 days (P = .02) and ED visits per child decreased by 16.5% (P = .002), with no difference in parental quality of life or hospitalizations. Only the association between more preventive care and fewer ED visits persisted in adjusted analysis (12.2% reduction; P = .03). For every 10% increase in acute care provision, ED visits per child and hospitalizations per child decreased by 18.1% (P = .02) and 16.5% (P < .001), respectively, persisting in adjusted analyses (ED visits 8.6% reduction, P = .02; hospitalizations 13.9%, P = .03). CONCLUSIONS: Children cared for in practices providing more preventive and acute asthma care had improved outcomes, both impairment and risk. Persistence of improved risk outcomes in the adjusted analyses suggests that practice-level interventions to increase asthma care may reduce childhood asthma disparities. PMID- 26868729 TI - A Perylene-Based Microporous Coordination Polymer Interacts Selectively with Electron-Poor Aromatics. AB - The design, synthesis, and properties of the new microporous coordination polymer UMCM-310 are described. The unique electronic character of the perylene-based linker enables selective interaction with electron-poor aromatics leading to efficient separation of nitroaromatics. UMCM-310 possesses high surface area and large pore size and thus permits the separation of large organic molecules based on adsorption rather than size exclusion. PMID- 26868728 TI - African American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization. AB - BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease of the upper airways that is often categorized into subtypes including "with" and "without" nasal polyps. However, the influence of multiple important epidemiologic factors, including race, on CRS has not been investigated. OBJECTIVE: The present study assessed various phenotypic characteristics of CRS in patients, living in the United States, with different racial backgrounds. METHODS: We performed a large retrospective cohort study of patients with CRS treated at a large urban tertiary care referral center in Chicago. RESULTS: African American (AA) patients with CRS living in Chicago were more likely to report hyposmia as a symptom of CRS. Furthermore, AA patients with CRS who failed medical therapy and required surgical intervention had a significantly higher frequency of nasal polyposis and aspirin-exacerbated respiratory disease, and a higher disease severity index on computed tomography imaging than did white patients with CRS. The increased polyposis in AAs was associated with increased hospitalization for asthma. There were no differences in the prevalence of atopy, asthma, atopic dermatitis, food allergy, duration of disease, or number of surgeries between different races. CONCLUSIONS: AAs with refractory CRS are at increased risk for nasal polyposis, smell loss, aspirin-exacerbated respiratory disease, and a greater severity of disease based on imaging, resulting in increased health care utilization. PMID- 26868730 TI - Chromatin immunoprecipitation and gene expression analysis of neuronal subtypes after fluorescence activated cell sorting. AB - BACKGROUND: With advances in cell capture, gene expression can now be studied in neuronal subtypes and single cells; however, studying epigenetic mechanisms that underlie these changes presents challenges. Moreover, chromatin immunoprecipitation (ChIP) protocols optimized for low cell number do not adequately address technical issues and cell loss while preparing tissue for fluorescence activated cell sorting (FACS). Developing a reliable FACS-ChIP protocol without the need for pooling tissue from multiple animals would enable study of epigenetic mechanisms in neuronal subtypes. METHODS: FACS was used to isolate dopamine 1 receptor (D1R) expressing cells from the nucleus accumbens (NAc) of a commercially available BAC transgenic mouse strain. D1R+ cells were used to study gene expression as well as histone modifications at gene promoters using a novel native ChIP protocol. RESULTS: Isolated cells had enrichment of the dopamine 1 receptor (D1R) mRNA and nearly undetectable levels of GFAP and D2R mRNA. ChIP analysis demonstrated the association of activating or repressive histone modifications with highly expressed or silent gene promoters, respectively. COMPARISON WITH EXISTING METHODS: The ChIP protocol developed in this paper enables characterization of histone modifications from ~30,000 FAC sorted neurons. CONCLUSIONS: We describe a one day FACS-ChIP protocol that can be applied to epigenetic studies of neuronal subtypes without pooling tissue. PMID- 26868731 TI - Minimally invasive highly precise monitoring of respiratory rhythm in the mouse using an epithelial temperature probe. AB - BACKGROUND: Respiration is one of the essential rhythms of life. The precise measurement of respiratory behavior is of great importance in studies addressing olfactory sensory processing or the coordination of orofacial movements with respiration. An ideal method of measurement should reliably capture the distinct phases of respiration without interfering with behavior. NEW METHOD: This new method involves chronic implantation of a thermistor probe in a previously undescribed hollow space located above the anterior portion of the nasal cavity without penetrating any soft epithelial tissues. RESULTS: We demonstrate the reliability and precision of the method in head-fixed and freely moving mice by directly comparing recorded signals with simultaneous measurements of chest movements and plethysmographic measurements of respiration. COMPARISON WITH EXISTING METHODS: Current methods have drawbacks in that they are either inaccurate or require invasive placement of temperature or pressure sensors into the sensitive nasal cavity, where they interfere with airflow and cause irritation and damage to the nasal epithelium. Furthermore, surgical placement within the posterior nasal cavity adjacent to the nasal epithelium requires extensive recovery time, which is not necessary with the described method. CONCLUSIONS: Here, we describe a new method for recording the rhythm of respiration in awake mice with high precision, without damaging or irritating the nasal epithelium. This method will be effective for measurement of respiration during experiments requiring free movement, as well as those involving imaging or electrophysiology. PMID- 26868732 TI - Mild traumatic brain injury-induced hippocampal gene expressions: The identification of target cellular processes for drug development. AB - BACKGROUND: Neurological dysfunction after traumatic brain injury (TBI) poses short-term or long-lasting health issues for family members and health care providers. Presently there are no approved medicines to treat TBI. Epidemiological evidence suggests that TBI may cause neurodegenerative disease later in life. In an effort to illuminate target cellular processes for drug development, we examined the effects of a mild TBI on hippocampal gene expression in mouse. METHODS: mTBI was induced in a closed head, weight drop-system in mice (ICR). Animals were anesthetized and subjected to mTBI (30g). Fourteen days after injury the ipsilateral hippocampus was utilized for cDNA gene array studies. mTBI animals were compared with sham-operated animals. Genes regulated by TBI were identified to define TBI-induced physiological/pathological processes. mTBI regulated genes were divided into functional groupings to provide gene ontologies. Genes were further divided to identify molecular/cellular pathways regulated by mTBI. RESULTS: Numerous genes were regulated after a single mTBI event that mapped to many ontologies and molecular pathways related to inflammation and neurological physiology/pathology, including neurodegenerative disease. CONCLUSIONS: These data illustrate diverse transcriptional changes in hippocampal tissues triggered by a single mild injury. The systematic analysis of individual genes that lead to the identification of functional categories, such as gene ontologies and then molecular pathways, illustrate target processes of relevance to TBI pathology. These processes may be further dissected to identify key factors that can be evaluated at the protein level to highlight possible treatments for TBI in human disease and potential biomarkers of neurodegenerative processes. PMID- 26868734 TI - Neck collar for restraining head and body movements in rats for behavioral task performance and simultaneous neural activity recording. AB - BACKGROUND: Head fixation has been one of the major methods in behavioral neurophysiology because it allows precision in stimulus application and behavioral assessment. Most neural recordings in awake monkeys have been obtained under head fixation, which is nowadays also being used in awake rodents. However, head fixation devices in rats often become unstable within several months, which increases risks for inflammation, infection, and necrosis of the bone and surrounding tissue. NEW METHOD: In this study we developed a novel non-invasive "neck collar system" for restraining the head and body movements of behaving rats. RESULTS: The attachment of the neck collar for 2-3 months did not affect the animals' health and welfare. Rats under neck-collar fixation could learn a behavioral task (standard delayed licking task) with the same efficiency as those under standard head fixation. They could also learn a more complicated task (delayed pro/anti-licking task) under neck-collar fixation and afterwards transfer their learning to the task under standard head fixation. Furthermore, we were able to record single-unit activity in rats under neck-collar fixation during the performance of the standard delayed licking task. COMPARISON WITH EXISTING METHOD(S): This system consists of economical materials and is easily constructed, and it enables head-restraint without surgery, thus eliminating the risk of inflammation or infection. CONCLUSIONS: We consider the neck-collar fixation developed in this study would be useful for restraining the head of a behaving rodent. PMID- 26868736 TI - Thai monks and lay nuns (mae chii) in urban health care. AB - In the process of defining their identity in relation to other social institutions, Thai monks and increasingly, lay nuns (mae chii), have been adopting social and community roles in rural areas. Studies conducted in the early 1980s and repeated more recently indicate that these can be adapted to suit urban situations such as paramedical roles in hospitals in which mae chii may prove more effective than monks as counsellors. But although the young scholar monks whose views were solicited were mostly open to such roles on the part of the mae chii, the majority were opposed to their full ordination as bhikkhuni. PMID- 26868737 TI - The indigenous psychiatry of Ladakh, part II: Narrative and metanarrative in the cultural control of dissociative states in the Himalayas. AB - In traditional Ladakh (NW India, Tibetan) men are less frequently sufferers from dissociative possession by 'witches' than are women, but they may be possessed by spirits of place, plausibly a consequence of their more outward focus on life beyond the household. Where possession leads to authorisation to practice as an oracle healer the 'afflicted' may gain in social status. Male possession is also induced through ritual meditation (visualisation) in monks destined to function as oracles in monastic festivals which have ancient links with traditional government. In these cases the individuals have usually had considerable experience and training in Buddhist mental yoga and have not experienced an initiatory illness. The metanarrative governing these occasions constrains village narratives as an aspect of social control by Buddhist authorities with a long history in the culture of Tibetan-speaking peoples. The functions of shamanic trance and its parallels in the post-modern West are considered. PMID- 26868735 TI - Weight and skin colour as predictors of vitamin D status: results of an epidemiological investigation using nationally representative data. AB - OBJECTIVE: Current US dietary recommendations for vitamin D vary by age. Recent research suggests that body weight and skin colour are also major determinants of vitamin D status. The objective of the present epidemiological investigation was to clarify the role of age as a predictor of vitamin D status, while accounting for body weight and skin colour, among a nationally representative sample. DESIGN: We calculated the mean serum 25-hydroxyvitamin D levels for the US population by age and weight, as well as by weight and race/ethnicity group. Multiple regression analyses were utilized to evaluate age and weight as predictors of vitamin D status: serum 25-hydroxyvitamin D levels with age alone, age and body weight, and age, body weight and their two-way interaction were modelled for the entire sample and each age subgroup. Graphical data were developed using B-spline non-linear regression. SETTING: National Health and Nutrition Examination Survey (31 934 unweighted cases). SUBJECTS: Individuals aged 1 year and older. RESULTS: There were highly significant differences in mean vitamin D status among US residents by weight and skin colour, with those having darker skin colour or higher body weight having worse vitamin D status. Although a significant factor, the impact of age on vitamin D status was notably less than the impact of body weight. CONCLUSIONS: Vitamin D status varied predominantly by body weight and skin colour. Recommendations by nutritionists for diet and supplementation needs should take this into account if vitamin D-related health disparities are to be meaningfully reduced across the USA. PMID- 26868733 TI - Novel pharmaceutical treatments for minimal traumatic brain injury and evaluation of animal models and methodologies supporting their development. AB - BACKGROUND: The need for effective pharmaceuticals within animal models of traumatic brain injury (TBI) continues to be paramount, as TBI remains the major cause of brain damage for children and young adults. While preventative measures may act to reduce the incidence of initial blunt trauma, well-tolerated drugs are needed to target the neurologically damaging internal cascade of molecular mechanisms that follow. Such processes, known collectively as the secondary injury phase, include inflammation, excitotoxicity, and apoptosis among other changes still subject to research. In this article positive treatment findings to mitigate this secondary injury in rodent TBI models will be overviewed, and include recent studies on Exendin-4, N-Acetyl-l-cycteine, Salubrinal and Thrombin. CONCLUSIONS: These studies provide representative examples of methodologies that can be combined with widely available in vivo rodent models to evaluate therapeutic approaches of translational relevance, as well as drug targets and biochemical cascades that may slow or accelerate the degenerative processes induced by TBI. They employ well-characterized tests such as the novel object recognition task for assessing cognitive deficits. The application of such methodologies provides both decision points and a gateway for implementation of further translational studies to establish the feasibility of clinical efficacy of potential therapeutic interventions. PMID- 26868738 TI - Fake malaria and hidden parasites-the ambiguity of malaria. AB - Lay perspectives and health-seeking behaviour for malaria were investigated in an ethnographic study carried out in a village in south-eastern Tanzania. The inhabitants have easy access to hospital services and education programmes, and as a result, biomedical knowledge on malaria is comparatively high. However, the cultural model of malaria does not always explain all the events that occur during an actual illness episode, e.g. when the disease cannot be detected at the hospital or the symptoms persist despite antimalarial treatment. Under these circumstances, the model of malaria may be complemented with the logic of witchcraft. This can lead people to consult sequentially both biomedical and traditional health services for the same illness episode. The consequences can include non-compliance with treatment or delay in seeking diagnosis or treatment. Our analysis offers elements for the understanding of aspects of the dynamics of reinterpretation and health-seeking behaviour for malaria, particularly in the phase after diagnosis and treatment at a biomedical health facility. The research is presented with an applied perspective. We propose specific recommendations that could be discussed with health promoters. PMID- 26868739 TI - 'Worms are our life', part I: Understandings of worms and the body among the Luo of western Kenya. AB - Perceptions of worms and their role in the body were studied among the people in a Luo village in western Kenya. Worms were found to be prominent in people's body image and ideas about illness. Two models applied to worms were distinguished analytically as 'traditional' and 'biomedical', referring to their sources, modes of transmission and relation to wider understandings of life. The first acknowledged worms as positive agents of both digestion and illness and aimed at maintaining a balanced relationship with them. The latter saw worms as dangerous intruders into bodily order and demanded their expulsion. Both models were used side by side or alternately by most people in the village, according to their individual preferences or to the specific context. The different attitudes to worms-one inclusive, the other exclusive-were related to wider concepts of dirt, pollution, affliction and evil, and shed light on people's understandings of the body and life. PMID- 26868740 TI - The powers of nature. AB - There has been a widespread tendency to interpret medical practices in Africa in terms of a spiritual or religious perspective, specifically linking medicine to spirit healing. Countering this tendency this paper emphasises the importance of an empirical herbal tradition in Malawi, and examines in detail the role of animals as medicine, especially highlighting their use as an activating medicine. Such use implies a distinctive ontology, a pan-vitalism that recognises the inherent powers of nature. PMID- 26868742 TI - Courses in medical anthropology: Germany. PMID- 26868746 TI - APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium. AB - PURPOSE: Squamous metaplasia is a common pathologic condition in ocular surface diseases for which there is no therapeutic medication in clinic. In this study, we investigated the effect of a small molecule, APR-246/PRIMA-1(Met), on squamous metaplasia in human conjunctival epithelium. METHODS: Human conjunctival explants were cultured for up to 12 days under airlifting conditions. Epithelial cell differentiation and proliferation were assessed by Cytokeratin 10 (K10), K14, K19, Pax6, MUC5AC, and p63 immunostaining patterns. beta-catenin and TCF-4 immunofluorescent staining and real-time PCR characterized Wnt signaling pathway involvement. Pterygium clinical samples were cultured under airlifting conditions with or without APR-246 for 4 days. p63, K10, beta-catenin, and TCF-4 expression in pterygial epithelium was determined by immunofluorescent staining and real time PCR. RESULTS: Airlift conjunctival explants resulted in increased stratification and intrastromal epithelial invagination. Such pathology was accompanied by increases in K10, K14, and p63 expression, whereas K19 and Pax6 levels declined when compared to those in freshly isolated tissue. On the other hand, APR-246 reversed all of these declines in K10, K14, and p63 expression. Furthermore, K19 and Pax6 increased along with rises in goblet cell density. These effects of APR-246 were accompanied by near restoration of normal conjunctival epithelial histology. APR-246 also reversed squamous metaplasia in pterygial epithelium that had developed after 4 days in ex vivo culture. CONCLUSIONS: Reductions in squamous metaplasia induced by APR-246 suggest it may provide a novel therapeutic approach in different squamous metaplasia-associated ocular surface diseases. PMID- 26868747 TI - (+)-Pentazocine Reduces NMDA-Induced Murine Retinal Ganglion Cell Death Through a sigmaR1-Dependent Mechanism. AB - PURPOSE: To evaluate, in vivo, the effects of the sigma-1 receptor (sigmaR1) agonist, (+)-pentazocine, on N-methyl-D-aspartate (NMDA)-mediated retinal excitotoxicity. METHODS: Intravitreal NMDA injections were performed in C57BL/6J mice (wild type [WT]) and sigmaR1-/- (sigmaR1 knockout [KO]) mice. Fellow eyes were injected with phosphate-buffered saline (PBS). An experimental cohort of WT and sigmaR1 KO mice was administered (+)-pentazocine by intraperitoneal injection, and untreated animals served as controls. Retinas derived from mice were flat-mounted and labeled for retinal ganglion cells (RGCs). The number of RGCs was compared between NMDA and PBS-injected eyes for all groups. Apoptosis was assessed using TUNEL assay. Levels of extracellular-signal-regulated kinases (ERK1/2) were analyzed by Western blot. RESULTS: N-methyl-D-aspartate induced a significant increase in TUNEL-positive nuclei and a dose-dependent loss of RGCs. Mice deficient in sigmaR1 showed greater RGC loss (~80%) than WT animals (~50%). (+)-Pentazocine treatment promoted neuronal survival, and this effect was prevented by deletion of sigmaR1. (+)-Pentazocine treatment resulted in enhanced activation of ERK at the 6-hour time point following NMDA injection. The (+) pentazocine-induced ERK activation was diminished in sigmaR1 KO mice. CONCLUSIONS: Targeting sigmaR1 activation prevented RGC death while enhancing activation of the mitogen-activated protein kinase (MAPK), ERK1/2. Sigma-1 receptor is a promising therapeutic target for retinal neurodegenerative diseases. PMID- 26868748 TI - Vascular Endothelial Growth Factor (VEGF) Concentration Is Underestimated by Enzyme-Linked Immunosorbent Assay in the Presence of Anti-VEGF Drugs. AB - PURPOSE: Commercially available enzyme-linked immunosorbent assay (ELISA) kits are often used to monitor vascular endothelial growth factor (VEGF) levels in exudative age-related macular degeneration. To test their accuracy, this study performed measurements using the ELISA kits in the presence of anti-VEGF drugs. METHODS: The concentrations of bevacizumab, pegaptanib, or ranibizumab at 28 days and aflibercept at 28 and 56 days after an injection were estimated based on previous pharmacokinetic studies. Vascular endothelial growth factor concentrations were measured with two widely used VEGF ELISA kits in the presence of anti-VEGF drugs or control mouse immunoglobulin G (IgG). The monocyte chemotactic protein-1 (MCP-1) ELISA kit was used as a non-VEGF ELISA control kit. RESULTS: The concentrations of aflibercept, bevacizumab, pegaptanib, and ranibizumab were estimated at 0.14 to 7.2, 4.9, 8.6, and 0.11 to 1.1 MUg/mL, respectively. ELISA underestimated the VEGF concentration 2- to 100-fold lower in the presence of an anti-VEGF drug, except for pegaptanib, at all VEGF concentrations tested (7.8-1500 pg/mL). Vascular endothelial growth factor at 1000 pg/mL was measured as 92, 150, and 170 pg/mL in the presence of aflibercept (7.2 MUg/mL), bevacizumab (4.9 MUg/mL), and ranibizumab (1.1 MUg/mL), respectively (all P < 0.0001), and the measured VEGF concentration decreased proportionately by 90% to 92% with aflibercept, 85% to 94% with bevacizumab, and 83% to 99% with ranibizumab. The control mouse IgG did not interfere with the measurement of VEGF. Ranibizumab did not affect the measurements with MCP-1 ELISA. CONCLUSIONS: Investigators should exercise caution when interpreting measurements of VEGF ELISA in patients being treated with an anti-VEGF drug. PMID- 26868750 TI - All-Optical Method to Assess Stromal Concentration of Riboflavin in Conventional and Accelerated UV-A Irradiation of the Human Cornea. AB - PURPOSE: We investigated the concentration of riboflavin in human donor corneas during corneal cross-linking using two-photon optical microscopy and spectrophotometry. METHODS: Eight corneal tissues were de-epithelialized and soaked with 20% dextran-enriched 0.1% riboflavin solution for 30 minutes. After stromal soaking, three tissues were irradiated using a 3 mW/cm2 UV-A device for 30 minutes and three tissues irradiated using a 10 mW/cm2 device for 9 minutes. Two additional tissues were used as positive controls. A Ti:sapphire laser at 810 nm was used to perform two-photon emission fluorescence (TPEF) and second harmonic generation axial scanning measurements in all specimens before and after stromal soaking and after UV-A irradiation. In addition, spectrophotometry was used to collect the absorbance spectra of each tissue at the same time intervals. Analysis of the absorbance spectra and TPEF signals provided measures of the concentration depth profile of riboflavin in corneal stroma. RESULTS: After stromal soaking, the average peak concentration of riboflavin (0.020% +/- 0.001%) was found between a stromal depth of 100 and 250 MUm; the concentration of riboflavin was almost constant up to 320 +/- 53 MUm depth, then decreased toward the endothelium, though riboflavin was still enriched in the posterior stroma (0.016%% +/- 0.001%). After conventional and accelerated UV-A irradiation, the concentration of riboflavin decreased uniformly 87% +/- 2% and 67% +/- 3% (P < 0.001), respectively. CONCLUSIONS: The combined use of two-photon optical microscopy and spectrophotometry provides relevant information for investigating the concentration of riboflavin in corneal stroma. The method can assist with the assessment of novel riboflavin formulations and different UV-A irradiation protocols. PMID- 26868749 TI - Extrafoveal Cone Packing in Eyes With a History of Retinopathy of Prematurity. AB - PURPOSE: To study the density and packing geometry of the extrafoveal cone photoreceptors in eyes with a history of retinopathy of prematurity (ROP). We used a multimodal combination of adaptive optics (AO) scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT). METHODS: Cones were identified in subjects (aged 14-26 years) with a history of ROP that was either severe and treated by laser ablation of avascular peripheral retina (TROP; n = 5) or mild and spontaneously resolved, untreated (UROP; n = 5), and in term-born controls (CT; n = 8). The AO-SLO images were obtained at temporal eccentricities 4.5 degrees , 9 degrees , 13.5 degrees , and 18 degrees using both confocal and offset apertures with simultaneous, colocal OCT images. Effects of group, eccentricity, and aperture were evaluated and the modalities compared. RESULTS: In the SLO images, cone density was lower and the packing pattern less regular in TROP, relative to CT and UROP retinae. Although SLO image quality appeared lower in TROP, root mean square (RMS) wavefront error did not differ among the groups. In TROP eyes, cone discrimination was easier in offset aperture images. There was no evidence of cone loss in the TROP OCT images. CONCLUSIONS: Low cone density in TROP confocal SLO images may have resulted from lower image quality. Since AO correction in these eyes was equivalent to that of the control group, and OCT imaging showed no significant cone loss, the optical properties of the inner retina or properties of the cones themselves are likely altered in a way that affects photoreceptor imaging. PMID- 26868751 TI - A Problem of Proportions in OCT-Based Morphometry and a Proposed Solution. PMID- 26868752 TI - The Characteristics of Lamina Cribrosa Defects in Myopic Eyes With and Without Open-Angle Glaucoma. AB - PURPOSE: We investigated the lamina cribrosa (LC) structural characteristics of myopic eyes with and without open-angle glaucoma (OAG) using enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT). METHODS: Defects in the LC in myopic eyes with and without OAG and normal eyes without myopia were evaluated using EDI SD-OCT. Among the two types of LC defects, disinsertion type and hole type, the associations among disinsertion type LC defects, myopia-related parameters of axial length (AL), maximal gamma-zone peripapillary atrophy (PPA) length, disc tilt angle, and the presence of glaucoma were evaluated. In addition, disinsertion type LC defects were divided into two subtypes, complete detachment type and triangular wedge type, and the numbers of the subtypes in myopic eyes with and without OAG were investigated. RESULTS: Defects in the LC were found more in myopic eyes with than without OAG (65.7% vs. 27.8%, P < 0.001). Of LC defects, disinsertion-type LC defects were found at the location of the gamma-zone PPA (R = 0.71, P < 0.001), while the location of hole type LC defects did not correlate with the location of the gamma-zone PPA (R = 0.07, P = 0.73). Of disinsertion-type LC defects, complete detachment-type defects predominated in myopic eyes with OAG, while triangular wedge-type defects were the most common in myopic eyes without OAG (P < 0.001; P < 0.001, respectively). In multivariate logistic regression analysis, disinsertion-type LC defects in myopic eyes were associated with AL, maximal PPA length, and disc tilt angle, as well as the presence of glaucoma. CONCLUSIONS: Given the strong correlation of disinsertion type LC defects with glaucoma and parameters related to myopia, such defects should be considered as biomarkers of glaucoma in myopic eyes. PMID- 26868753 TI - Ocular Outcomes Comparison Between 14- and 70-Day Head-Down-Tilt Bed Rest. AB - PURPOSE: To compare ocular outcomes in healthy subjects undergoing 14- and/or 70 day head-down-tilt (HDT) bed rest (BR). METHODS: Participants were selected by using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects maintained a 6 degrees HDT position for 14 and/or 70 consecutive days. Weekly ophthalmologic examinations were performed in the sitting (pre/post-BR only) and HDT positions. Mixed-effects linear models compared pre- and post-HDT BR observations between 14- and 70-day HDT BR in best corrected visual acuity, spherical equivalent, intraocular pressure (IOP), Spectralis OCT retinal nerve fiber layer thickness, peripapillary and macular retinal thicknesses. RESULTS: Sixteen and six subjects completed the 14- and 70 day HDT BR studies, respectively. The magnitude of HDT BR-induced changes was not significantly different between the two studies for all outcomes, except the superior (mean pre/post difference of 14- vs. 70-day HDT BR: +4.69 MUm versus +11.50 MUm), nasal (+4.63 MUm versus +11.46 MUm), and inferior (+4.34 MUm versus +10.08 MUm) peripapillary retinal thickness. A +1.42 mm Hg and a +1.79 mm Hg iCare IOP increase from baseline occurred during 14- and 70-day HDT BR, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable. CONCLUSIONS: Seventy-day HDT BR induced greater peripapillary retinal thickening than 14-day HDT BR, suggesting that time may affect the amount of optic disc swelling. Spectralis OCT detected retinal nerve fiber layer thickening post BR, without clinical signs of optic disc edema. A small IOP increase during BR subsided post HDT BR. Such changes may have resulted from BR-induced cephalad fluids shift. The HDT BR duration may be critical for replicating microgravity-related ophthalmologic changes observed in astronauts on >=6-month spaceflights. PMID- 26868754 TI - Involvement of AMPA Receptor and Its Flip and Flop Isoforms in Retinal Ganglion Cell Death Following Oxygen/Glucose Deprivation. AB - PURPOSE: The alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors (AMPAR) subunits can be posttranscriptionally modified by alternative splicing forming flip and flop isoforms. We determined if an ischemia-like insult to retinal ganglion cells (RGCs) increases AMPAR susceptibility to s-AMPA mediated excitotoxicity through changes in posttranscriptional modified isoforms. METHODS: Purified neonatal rat RGCs were subjected to either glucose deprivation (GD) or oxygen/glucose deprivation (OGD) conditions followed by treatment with either 100 MUM s-AMPA or Kainic acid. A live-dead assay and caspase 3 assay was used to assess cell viability and apoptotic changes, respectively. We used JC-1 dye and dihydroethidium to measure mitochondria depolarization and reactive oxygen species (ROS), respectively. Calcium imaging with fura-2AM was used to determine intracellular calcium, while the fluorescently-labeled probe, Nanoprobe1, was used to detect calcium-permeable AMPARs. Quantitative PCR (qPCR) analysis was done to determine RNA editing sites AMPAR isoforms. RESULTS: Glucose deprivation, as well as an OGD insult followed by AMPAR stimulation, produced a significant increase in RGC death. Retinal ganglion cell death was independent of caspase 3/7 activity, but was accompanied by increased mitochondrial depolarization and increased ROS production. This was associated with an elevated intracellular Ca(2+) and calcium permeable-AMPARs. The mRNA expression of GLUA2 and GLUA3 flop isoform decreased significantly, while no appreciable changes were found in the corresponding flip isoforms. There were no changes in the Q/R editing of GLUA2, while R/G editing of GLUA2 flop declined under these conditions. CONCLUSIONS: Following oxidative injury, RGCs become more susceptible to AMPAR-mediated excitotoxicity. RNA editing and changes in alternative spliced flip and flop isoforms of AMPAR subunits may contribute to increased RGC death. PMID- 26868755 TI - Peripapillary Retinal Nerve Fiber Layer Swelling Predicts Peripapillary Atrophy in a Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy. AB - PURPOSE: To determine the relationship between peripapillary retinal nerve fiber layer (PRNFL) swelling and eventual PRNFL atrophy, and between PRNFL swelling/atrophy and neural function, in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (pNAION). METHODS: pNAION was induced in five normal, adult male rhesus monkeys by laser activation of intravenously injected rose bengal at the optic nerve head. Spectral-domain optical coherence tomography measurements of the PRNFL were performed at baseline; 1 day; 1, 2, and 4 weeks; and several later times over a period of an additional 2 to 3 months. Simultaneous pattern-reversal electroretinograms (PERGs) and visual evoked potentials (VEPs) were recorded and color fundus photographs taken at the same time points. RESULTS: In all cases, initial PRNFL swelling was associated with atrophy, and the greater the initial swelling, the greater the degree of eventual atrophy (r = 0.65, P = 0.0002). The change in PRNFL thickness closely correlated with VEP amplitude loss (r = 0.90), although this relationship was only a strong trend (P = 0.083). Furthermore, VEP amplitude loss closely correlated with PERG N95 amplitude loss (r = 0.80, P = 0.00002). CONCLUSIONS: In our model of human NAION, the degree of initial PRNFL swelling correlated with the severity of atrophy. Areas that did not swell developed little to no atrophy. The amount of PRNFL loss was reflected in VEP and PERG N95 amplitude reductions. PMID- 26868757 TI - The complete mitochondrial genome of the Tibetan fox (Vulpes ferrilata) and implications for the phylogeny of Canidae. AB - Canidae is a family of carnivores comprises about 36 extant species that have been defined as three distinct monophyletic groups based on multi-gene data sets. The Tibetan fox (Vulpes ferrilata) is a member of the family Canidae that is endemic to the Tibetan Plateau and has seldom been in the focus of phylogenetic analyses. To clarify the phylogenic relationship of V. ferrilata between other canids, we sequenced the mitochondrial genome and firstly attempted to clarify the relative phylogenetic position of V. ferrilata in canids using the complete mitochondrial genome data. The mitochondrial genome of the Tibetan fox was 16,667 bp, including 37 genes (13 protein-coding genes, 2 rRNA, and 22 tRNA) and a control region. A comparison analysis among the sequenced data of canids indicated that they shared a similar arrangement, codon usage, and other aspects. A phylogenetic analysis on the basis of the nearly complete mtDNA genomes of canids agreed with three monophyletic clades, and the Tibetan fox was highly supported as a sister group of the corsac fox within Vulpes. The estimation of the divergence time suggested a recent split between the Tibetan fox and the corsac fox and rapid evolution in canids. There was no genetic evidence for positive selection related to high-altitude adaption for the Tibetan fox in mtDNA and following studies should pay more attention to the detection of positive signals in nuclear genes involved in energy and oxygen metabolisms. PMID- 26868756 TI - The production of human glucocerebrosidase in glyco-engineered Nicotiana benthamiana plants. AB - For the production of therapeutic proteins in plants, the presence of beta1,2 xylose and core alpha1,3-fucose on plants' N-glycan structures has been debated for their antigenic activity. In this study, RNA interference (RNAi) technology was used to down-regulate the endogenous N-acetylglucosaminyltransferase I (GNTI) expression in Nicotiana benthamiana. One glyco-engineered line (NbGNTI-RNAi) showed a strong reduction of plant-specific N-glycans, with the result that as much as 90.9% of the total N-glycans were of high-mannose type. Therefore, this NbGNTI-RNAi would be a promising system for the production of therapeutic glycoproteins in plants. The NbGNTI-RNAi plant was cross-pollinated with transgenic N. benthamiana expressing human glucocerebrosidase (GC). The recombinant GC, which has been used for enzyme replacement therapy in patients with Gaucher's disease, requires terminal mannose for its therapeutic efficacy. The N-glycan structures that were presented on all of the four occupied N glycosylation sites of recombinant GC in NbGNTI-RNAi plants (GC(gnt1) ) showed that the majority (ranging from 73.3% up to 85.5%) of the N-glycans had mannose type structures lacking potential immunogenic beta1,2-xylose and alpha1,3-fucose epitopes. Moreover, GC(gnt1) could be taken up into the macrophage cells via mannose receptors, and distributed and taken up into the liver and spleen, the target organs in the treatment of Gaucher's disease. Notably, the NbGNTI-RNAi line, producing GC, was stable and the NbGNTI-RNAi plants were viable and did not show any obvious phenotype. Therefore, it would provide a robust tool for the production of GC with customized N-glycan structures. PMID- 26868759 TI - Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer. AB - Mesenchymal stem cells (MSCs) are characterized to have the capacity of self renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms in the regulation of mitochondrial metabolism of MSCs may ultimately improve therapeutic outcomes of stem cell therapy in the future. PMID- 26868758 TI - Energy metabolism in the acquisition and maintenance of stemness. AB - Energy metabolism is traditionally considered a reactive homeostatic system addressing stage-specific cellular energy needs. There is however growing appreciation of metabolic pathways in the active control of vital cell functions. Case in point, the stem cell lifecycle--from maintenance and acquisition of stemness to lineage commitment and specification--is increasingly recognized as a metabolism-dependent process. Indeed, metabolic reprogramming is an early contributor to the orchestrated departure from or reacquisition of stemness. Recent advances in metabolomics have helped decipher the identity and dynamics of metabolic fluxes implicated in fueling cell fate choices by regulating the epigenetic and transcriptional identity of a cell. Metabolic cues, internal and/or external to the stem cell niche, facilitate progenitor pool restitution, long-term tissue renewal or ensure adoption of cytoprotective behavior. Convergence of energy metabolism with stem cell fate regulation opens a new avenue in understanding primordial developmental biology principles with future applications in regenerative medicine practice. PMID- 26868761 TI - Relevance of Damped Harmonic Oscillation for Modeling the Training Effects on Daily Physical Performance Capacity in Team Sport. AB - CONTEXT: Positive and negative effects of training induce apparent oscillations of performance, suggesting that the delayed cumulative effects of training on daily performance capacity (DPC) are best fitted by sine waves damped over time. PURPOSE: To compare the criterion validity of the impulse-response (IR) model of Banister et al and the damped harmonic oscillation (DHO) model for quantifying the training load (TL)-DPC relationship. METHODS: Six female professional volleyball players (20.8 +/- 2.4 y) were monitored using the session rating of perceived exertion (sRPE) for 9 mo to quantify TL. Countermovement-jump (CMJ) and 4-step-approach-CMJ (4sCMJ) performances were recorded once a month. Parameters of models were determined by minimizing residual-sum squares between predicted and real performances with a nonlinear regression. RESULTS: DPC was best fitted by the DHO model rather than the IR model (CMJ, R2 = .80 +/-.08 and.69 +/-.20, respectively; 4sCMJ, R2 = .86 +/- .09 and .67 +/- .29, respectively). The damping parameter theta and the period T were positively correlated with age (rho = 0.81, P < .05, and rho = 0.86, P < .02, respectively). CONCLUSIONS: The DHO model is a useful tool for modeling DPC as the sum of the delayed DPCs from the consecutive training and recovery days. DPC could be considered the expression of the individual process of accumulation and dissipation of fatigue induced by training. DHO-model parameters were correlated with age, which prompts one to postulate that expertise has a major influence on DPC. The DHO model will help coaches develop a greater understanding of training effects and make monitoring of the training process more effective. PMID- 26868760 TI - Development of a Reading Accessibility Index Using the MNREAD Acuity Chart. AB - IMPORTANCE: We define a Reading Accessibility Index for evaluating reading in individuals with normal and low vision. OBJECTIVE: To compare the Reading Accessibility Index with data from the Impact of Cataracts on Mobility (ICOM) study. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a secondary data analysis from the ICOM study performed between July 1, 2014, and September 20, 2015, at 12 eye clinics in Alabama from October 1, 1994, through March 31, 1996. Participants were 321 adults with cataract (n = 92), pseudophakia (n = 131), or natural crystalline lenses without cataract (n = 98). MAIN OUTCOMES AND MEASURES: The Reading Accessibility Index (hereafter referred to using the abbreviation ACC for the first 3 letters of Accessibility) is defined as an individual's mean reading speed measured across the 10 largest print sizes on the MNREAD Acuity Chart (Precision Vision) (0.4-1.3 logarithm of the minimum angle of resolution at 40 cm), normalized by 200 words per minute, which was the mean value for a group of 365 normally sighted young adults. The ACC is a single-value measure that captures an individual's range of accessible print sizes and reading fluency within this range. RESULTS: The study cohort comprised 321 participants. Their age range was 55 to 85 years, and 157 (48.9%) were female. The ACCs for the ICOM study participants ranged from 0.19 to 1.33, where 1.00 is the mean value for normally sighted young adults. The ACC for the cataract group (mean [SD], 0.65 [0.18]) was significantly lower than that for the pseudophakia group (mean [SD], 0.77 [0.16]) and the control group (mean [SD], 0.76 [0.19]) (P < .001 for both). The correlation between the ACC and Early Treatment Diabetic Retinopathy Study visual acuity (r = -0.22) and Pelli-Robson contrast sensitivity (r = 0.20) was weaker than that with a reading-related measure of instrumental activities of daily living (r = -0.60) (P < .001 for both). CONCLUSIONS AND RELEVANCE: The ACC represents an individual's access to text across the range of print sizes found in everyday life. Its calculation does not rely on curve fitting and provides a direct comparison with the performance of normally sighted individuals. Changes in an individual's ACC might be used to evaluate the effect of ophthalmic treatment, rehabilitation programs, or assistive technology on reading accessibility. Data from the ICOM study show that the ACC reflects characteristics of reading performance in everyday life and is sensitive to improved reading accessibility for pseudophakic eyes. PMID- 26868762 TI - Correction to "Effect of Age on The Hepatocellularity Number for Wistar Rats". PMID- 26868763 TI - Microstructural Characterization of Fried Potato Disks Using X-Ray Micro Computed Tomography. AB - Microstructural properties play a key role to affect oil uptake and product quality during frying of foods. The objective of this study was to observe the complex microstructural changes and mass transfer mechanisms in potato disks during frying. The potato disks of 1.65 mm thickness were fried at 190 degrees C for 0, 20, 40, 60, and 80 s. X-ray micro-computed tomography (CT) was used for 3 dimensional (3D) imaging of microstructure of porous potato disks. Total porosity, pore size distribution, oil content, and air content of potato disks were calculated from resulting 3D data sets. Oil and air content measured by analysis of micro-CT images followed trends similar to Soxtec and gas pycnometry methods, respectively. Image analysis showed a significant change in pore size distribution as a function of frying time. Frying time was also observed to have an effect on tortuosity, which is an important microstructural fluid transport property. Tortuosity was measured by path length ratio method from 3D data sets obtained from image analysis. A linear inverse relationship was observed between porosity and tortuosity where tortuosity decreased with the increase of porosity. It was also observed that during frying, oil content increased with the decrease of tortuosity. This phenomenon indicated that the lower tortuosity created a less complicated and sinuous path, thus resulting in less resistance to oil penetration. Micro-CT technique can serve as an effective tool for elucidating microstructure of fried foods, and can provide complementary information to conventional lab techniques. PMID- 26868765 TI - AAP President's Address. PMID- 26868766 TI - Multiple Barriers to the Evolution of Alternative Gene Orders in a Positive Strand RNA Virus. AB - The order in which genes are organized within a genome is generally not conserved between distantly related species. However, within virus orders and families, strong conservation of gene order is observed. The factors that constrain or promote gene-order diversity are largely unknown, although the regulation of gene expression is one important constraint for viruses. Here we investigate why gene order is conserved for a positive-strand RNA virus encoding a single polyprotein in the context of its authentic multicellular host. Initially, we identified the most plausible trajectory by which alternative gene orders could evolve. Subsequently, we studied the accessibility of key steps along this evolutionary trajectory by constructing two virus intermediates: (1) duplication of a gene followed by (2) loss of the ancestral gene. We identified five barriers to the evolution of alternative gene orders. First, the number of viable positions for reordering is limited. Second, the within-host fitness of viruses with gene duplications is low compared to the wild-type virus. Third, after duplication, the ancestral gene copy is always maintained and never the duplicated one. Fourth, viruses with an alternative gene order have even lower fitness than viruses with gene duplications. Fifth, after more than half a year of evolution in isolation, viruses with an alternative gene order are still vastly inferior to the wild-type virus. Our results show that all steps along plausible evolutionary trajectories to alternative gene orders are highly unlikely. Hence, the inaccessibility of these trajectories probably contributes to the conservation of gene order in present-day viruses. PMID- 26868767 TI - A Segregating Inversion Generates Fitness Variation in Yellow Monkeyflower (Mimulus guttatus). AB - Polymorphic chromosomal rearrangements can bind hundreds of genes into single genetic loci with diverse effects. Rearrangements are often associated with local adaptation and speciation and may also be an important component of genetic variation within populations. We genetically and phenotypically characterize a segregating inversion (inv6) in the Iron Mountain (IM) population of Mimulus guttatus (yellow monkeyflower). We initially mapped inv6 as a region of recombination suppression in three F2 populations resulting from crosses among IM plants. In each case, the F1 parent was heterozygous for a derived haplotype, homogenous across markers spanning over 5 Mb of chromsome 6. In the three F2 populations, inv6 reduced male and female fitness components. In addition,i nv6 carriers suffered an ~30% loss of pollen viability in the field. Despite these costs, inv6 exists at moderate frequency (~8%) in the natural population, suggesting counterbalancing fitness benefits that maintain the polymorphism. Across 4 years of monitoring in the field, inv6 had an overall significant positive effect on seed production (lifetime female fitness) of carriers. This benefit was particularly strong in harsh years and may be mediated (in part) by strong positive effects on flower production. These data suggest that opposing fitness effects maintain an intermediate frequency, and as a consequence, inv6 generates inbreeding depression and high genetic variance. We discuss these findings in relation to the theory of inbreeding depression and the maintenance of fitness variation. PMID- 26868768 TI - Estimating Modifying Effect of Age on Genetic and Environmental Variance Components in Twin Models. AB - Twin studies have been adopted for decades to disentangle the relative genetic and environmental contributions for a wide range of traits. However, heritability estimation based on the classical twin models does not take into account dynamic behavior of the variance components over age. Varying variance of the genetic component over age can imply the existence of gene-environment (G*E) interactions that general genome-wide association studies (GWAS) fail to capture, which may lead to the inconsistency of heritability estimates between twin design and GWAS. Existing parametricG*Einteraction models for twin studies are limited by assuming a linear or quadratic form of the variance curves with respect to a moderator that can, however, be overly restricted in reality. Here we propose spline-based approaches to explore the variance curves of the genetic and environmental components. We choose the additive genetic, common, and unique environmental variance components (ACE) model as the starting point. We treat the component variances as variance functions with respect to age modeled by B-splines or P splines. We develop an empirical Bayes method to estimate the variance curves together with their confidence bands and provide an R package for public use. Our simulations demonstrate that the proposed methods accurately capture dynamic behavior of the component variances in terms of mean square errors with a data set of >10,000 twin pairs. Using the proposed methods as an alternative and major extension to the classical twin models, our analyses with a large-scale Finnish twin data set (19,510 MZ twins and 27,312 DZ same-sex twins) discover that the variances of the A, C, and E components for body mass index (BMI) change substantially across life span in different patterns and the heritability of BMI drops to ~50% after middle age. The results further indicate that the decline of heritability is due to increasing unique environmental variance, which provides more insights into age-specific heritability of BMI and evidence ofG*Einteractions. These findings highlight the fundamental importance and implication of the proposed models in facilitating twin studies to investigate the heritability specific to age and other modifying factors. PMID- 26868769 TI - Single Molecule Microscopy Reveals an Increased Hyaluronan Diffusion Rate in Synovial Fluid from Knees Affected by Osteoarthritis. AB - Osteoarthritis is a common and progressive joint disorder. Despite its widespread, in clinical practice only late phases of osteoarthritis that are characterized by severe joint damage are routinely detected. Since osteoarthritis cannot be cured but relatively well managed, an early diagnosis and thereby early onset of disease management would lower the burden of osteoarthritis. Here we evaluated if biophysical parameters of small synovial fluid samples extracted by single molecule microscopy can be linked to joint damage. In healthy synovial fluid (ICRS-score < 1) hyaluronan showed a slower diffusion (2.2 MUm(2)/s, N = 5) than in samples from patients with joint damage (ICRS-score > 2) (4.5 MUm(2)/s, N = 16). More strikingly, the diffusion coefficient of hyaluronan in healthy synovial fluid was on average 30% slower than expected by sample viscosity. This effect was diminished or missing in samples from patients with joint damage. Since single molecule microscopy needs only microliters of synovial fluid to extract the viscosity and the specific diffusion coefficient of hyaluronan this method could be of use as diagnostic tool for osteoarthritis. PMID- 26868770 TI - Knowledge-guided mutation in classification rules for autism treatment efficacy. AB - Data mining methods in biomedical research might benefit by combining genetic algorithms with domain-specific knowledge. The objective of this research is to show how the evolution of treatment rules for autism might be guided. The semantic distance between two concepts in the taxonomy is measured by the number of relationships separating the concepts in the taxonomy. The hypothesis is that replacing a concept in a treatment rule will change the accuracy of the rule in direct proportion to the semantic distance between the concepts. The method uses a patient database and autism taxonomies. Treatment rules are developed with an algorithm that exploits the taxonomies. The results support the hypothesis. This research should both advance the understanding of autism data mining in particular and of knowledge-guided evolutionary search in biomedicine in general. PMID- 26868771 TI - Thioxanthone in apolar solvents: ultrafast internal conversion precedes fast intersystem crossing. AB - The photophysics of thioxanthone dissolved in cyclohexane was studied by femtosecond fluorescence and transient absorption spectroscopy. From these experiments two time constants of ~400 fs and ~4 ps were retrieved. With the aid of quantum chemically computed spectral signatures and rate constants for intersystem crossing, the time constants were assigned to the underlying processes. Ultrafast internal conversion depletes the primarily excited (1)pipi* state within ~400 fs. The (1)npi* state populated thereby undergoes fast intersystem crossing (~4 ps) yielding the lowest triplet state of (3)pipi* character. PMID- 26868773 TI - The history of everything, dental. PMID- 26868772 TI - Prevalence of HPV infection among 28,457 Chinese women in Yunnan Province, southwest China. AB - Human papillomavirus (HPV) infection plays a key role in the development of cervical cancer. The aim of the current study was to investigate the HPV type distribution in Chinese women from Yunnan Province, southwest China. A total of 28,457 individuals ranging in age from 17-84 years were recruited from 13 clinical hospitals located in 10 different regions of Yunnan Province. Cervicovaginal swabs were collected from each participant, and HPV screening was performed using Luminex xMAP technology. Our results showed that the HPV prevalence was 12.9% in Yunnan Province. Overall, 10.6% of the individuals were positive for a single HPV type, and 2.3% were positive for multiple types. Among the individuals who tested positive for a single HPV type and multiple HPV types, the three most prevalent high-risk types were 52, 16, and 58. Age subgroup analysis showed two peaks for the frequencies of single and multiple HPV infections, one for the group of women under 25 years old, and the other for the group over 56 years old. Here, we present data regarding the prevalence and type distribution of HPV infection, which will aid in the estimation of the potential clinical benefit and cost-effectiveness of HPV screening and vaccination in China. PMID- 26868774 TI - Special care dentistry: Treating autistic children. PMID- 26868775 TI - Dental impressions: Metal rim lock trays. PMID- 26868776 TI - Emergency dentistry: Three primary reasons. PMID- 26868777 TI - Endodontics: Gross misinterpretation. PMID- 26868778 TI - Blatant ignorance. PMID- 26868779 TI - Hansrani responds. PMID- 26868780 TI - Dental volunteering: Rewarding and affirming. PMID- 26868781 TI - Dental public health: The late Professor Aubrey Sheiham. PMID- 26868782 TI - Accidental cheek fistula. PMID- 26868783 TI - Campaign launched to reduce kids' hefty sugar intake. PMID- 26868784 TI - Landmark collaboration reviews links between general and oral health. PMID- 26868785 TI - First dental clinical leadership fellowships launched. PMID- 26868786 TI - Investigation: Building a platform for better oral health. PMID- 26868788 TI - Tim explores the link between caries and patient behaviour. PMID- 26868789 TI - A dentist's life: Making people smile is the best part of my job. PMID- 26868790 TI - Foundation dentist spots fake. PMID- 26868791 TI - Simon Rogers: 'Ultimately we need better access for patients'. PMID- 26868792 TI - Heather Pope: 'A challenge will be managing expectations of what can realistically be done'. PMID- 26868793 TI - Surgery: a patient's perspective and lessons learnt. AB - This article discusses a hospital experience from the point of view of a patient, in this case a healthcare worker herself - a dental student. The author relates her experience of a three-day hospital stay and appendectomy, during which time she experienced the breaking of bad news, the consent process, and the importance of good communication - all from the patient's viewpoint. PMID- 26868794 TI - Medical risk assessment in dentistry: use of the American Society of Anesthesiologists Physical Status Classification. AB - BACKGROUND: Medical risk assessment is essential to safe patient management and the delivery of appropriate dental care. The American Society of Anesthesiologists Physical Status (ASA PS) Classification is widely used within medicine and dentistry, but has received significant criticism. This is the first UK survey to assess the consistency of medical risk assessment in dentistry. AIMS: (i) To determine the use and consistency of the ASA PS among dentists and anaesthetists. (ii) To consider the appropriateness of the ASA PS in relation to dental treatment planning and delivery of care. METHOD: A cross-sectional online questionnaire was distributed to anaesthetists and dental practitioners in general practice, community and hospital dental services. Questions focused on professional backgrounds, use of the ASA PS, alternative approaches to risk assessment in everyday practice and scoring of eight hypothetical patients using ASA PS. RESULTS: There were 101 responses, 82 were complete. Anaesthetists recorded ASA PS score more frequently than dental practitioners and found it more useful. Inconsistencies were evident in the assignment of ASA PS scores both between and within professional groups. CONCLUSION: Many dental practitioners did not use or find ASA PS helpful, with significant inconsistencies in its use. An awareness of alternative assessment scales may be useful across settings. Accepting its limitations, it would be helpful for all dentists to be educated in ASA PS and its use in medical risk assessment, particularly in relation to conscious sedation. PMID- 26868795 TI - Removal techniques for failed implants. AB - The use of dental implants is an accepted and predictable way of replacing missing or lost teeth. However, implants can and will fail and there are a variety of reasons why this occurs, which the practitioner should understand. In some instances failed implants may require removal and, therefore, practitioners should be aware of techniques that can be used to remove failed implants to potentially enable future rehabilitation of an edentulous region. PMID- 26868800 TI - Articaine buccal infiltration vs lidocaine inferior dental block - a review of the literature. AB - AIM: This paper aims to compare the effectiveness of articaine buccal infiltrations (BIs) and lidocaine inferior alveolar nerve blocks (IANBs) for inducing pulpal anaesthesia in mandibular molars. METHOD: Studies which compared articaine BIs with lidocaine IANBs were identified by completing a full literature search using the MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. Only studies that used permanent mandibular molars were included. Two papers were accepted for appraisal. RESULTS: It was found that 55.6-69.2% and 65.4-70.4% of lidocaine IANBs and articaine BIs were successful, respectively. Neither study was able to determine a significant difference between the two techniques. CONCLUSIONS: Articaine BIs are no more effective than lidocaine IANBs and the decision of which method to practice should be based on patient selection, cost and time efficiency. The studies present a number of weaknesses in their design, hence, the level of evidence they provide is inconclusive. Further investigation in this field is warranted. PMID- 26868801 TI - Oral health promotion: the economic benefits to the NHS of increased use of sugarfree gum in the UK. AB - INTRODUCTION: The effect of sugarfree gum (SFG) on the prevention of dental caries has been established for some time. With increased constraints placed on healthcare budgets, the importance of economic considerations in decision-making about oral health interventions has increased. The aim of this study was to demonstrate the potential cost savings in dental care associated with increased levels of SFG usage. METHODS: The analysis examined the amount of money which would hypothetically be saved if the UK 12-year-old population chewed more SFG. The number of sticks chewed per year and the caries risk reduction were modelled to create a dose response curve. The costs of tooth restoration, tooth extraction in primary care settings and under general anaesthetic were considered, and the effects of caries reduction on these costs calculated. RESULTS: If all members of the UK 12-year-old population chewed SFG frequently (twice a day), the potential cost savings for the cohort over the course of one year were estimated to range from L1.2 to L3.3 million and if they chewed three times a day, L8.2 million could be saved each year. Sensitivity analyses of the key parameters demonstrated that cost savings would still be likely to be observed even in scenarios with less significant increases in SFG use. CONCLUSION: This study shows that if levels of SFG usage in the teenage population in the UK could be increased, substantial cost savings might be achieved. PMID- 26868802 TI - Developing assessment: involving the sessional clinical teacher. AB - Assessment development is a fundamental element of curriculum management and a requirement for providers of education to consistently demonstrate attainment of educational standards. Development of authentic, valid and reliable assessment is, however, both challenging and resource intensive. In the UK, dental education standards are regulated by the General Dental Council (GDC). The 'safe beginner' is the threshold determined by the GDC for the passing student - but how do we apply this? This article describes an approach the School of Dental Sciences at Newcastle University has adopted to address the challenges associated with developing assessments. Sessional clinical teachers contribute a significant proportion of the clinical supervision within the BDS programme and also have a good appreciation of both the standard and concept of the 'safe beginner'. By implementing a process of active timetable management, we have identified time where this group could contribute to assessment development. We believe that aspects, which could be enhanced by their involvement, include writing, validation, standard-setting and utilisation of assessment. To achieve this, we recognise a requirement for investment in careful manpower planning and training, but consider that it is realistic and beneficial to include sessional clinical teachers in this essential part of learning and teaching. PMID- 26868803 TI - Dental witness seminars: dentistry in the UK since 1948. AB - Witness seminars attempt to get behind the scenes of advances and developments to find out what really happened at certain times; they are not intended to provide a detailed history of events. This paper presents highlights from the five John McLean Archive witness seminars, providing an instructional collection of memories and insights into the world of dentistry in the UK since the late 1940s. It is concluded that future change will be seen as a welcome constant to be used for the benefit of the profession and the patients and communities it serves. PMID- 26868815 TI - Aubrey Sheiham. PMID- 26868816 TI - Headache of neurally mediated syncope. AB - BACKGROUND: Neurally mediated syncope and migraine have a complex relationship. AIM: The aim of this study was to investigate whether patients developing syncope in the laboratory would experience migraine. METHODS: Thirty-one consecutive patients were evaluated for precipitation of headache during head-up tilt (HUT) induced syncope (reduction of systolic blood pressure [SBP] >20 mmHg and prodromal symptoms with or without loss of consciousness). Autonomic functions were assessed using heart rate response to deep breathing (HRDB), Valsalva maneuver and HUT. Blood pressure and heart rate (via electrocardiography) were continuously monitored. Headache diagnosis was based on ICHD-3 criteria. RESULTS: Eighteen patients (58%) experienced syncope without headache and 13 (42%) had syncope and headache (SH). No difference was observed in time of syncope onset, reduction in SBP, Valsalva ratio, HRDB or tachycardia during initial 10 minutes of HUT. Of the 13 SH patients, 11 (85%) had a past history of migraine. Two reported headache just before tilt, eight developed headache during tilt and three developed headache only after tilt. Headache resolved within 1-15 minutes in 10 out of 13 patients. No patient experienced migraine. CONCLUSIONS: Syncope did not precipitate migraine. Headache during syncope may be due to cerebral hypoperfusion, and cerebral hyperperfusion may cause post-syncopal headache. PMID- 26868817 TI - Cardiac monitoring of high-dose verapamil in cluster headache: An international Delphi study. AB - BACKGROUND: In many patients, high-dose verapamil (HDV) is the only effective prophylactic treatment for cluster headache. Although cardiac adverse events and EKG abnormalities are relatively common, evidence-based guidelines for screening and monitoring patients on HDV are lacking. GOAL AND METHODS: Using the Delphi approach, we interviewed 22 international clinical experts in cardiac rhythm disorders to formulate EKG guidelines for the pretreatment screening and monitoring of cluster headache patients using HDV. RESULTS: The panel agreed only on performing pretreatment EKG to screen for pre-existing cardiac arrhythmia. Pretreatment EKG was deemed not necessary by most panel members for patients who did not have cardiac adverse events during a previous period of cluster headache attacks treated with HDV. Half the panel advised Holter EKG for patients on verapamil >= 480 mg/day. The highest recommended daily doses varied between 240 and 960 mg. Contraindications for use of verapamil largely followed FDA guidelines. DISCUSSION: Experts in cardiac rhythm disorders agreed on pretreatment EKG monitoring, but no consensus was reached on EKG monitoring during HDV treatment and around dose adjustments. PMID- 26868818 TI - Migraine and endothelial function: The HUNT3 Study. AB - BACKGROUND: Reduced endothelial function is associated with elevated risk of cardiovascular disease, but evidence on the association between migraine and endothelial function is conflicting. The aim of this population-based study was to examine the relationship between flow-mediated dilatation (FMD) and migraine with aura, migraine without aura and tension-type headache. METHODS: In the third Nord-Trondelag Healthy Study (HUNT3) FMD was measured by ultrasound during reactive hyperaemia of the brachial artery in a sample of 4739 healthy adult participants, 3929 of whom answered headache questions. The cross-sectional association between different headache diagnoses and FMD was evaluated by logistic regression, using a categorical approach. RESULTS: Mean FMD did not differ between the headache groups and headache-free controls. In multi-adjusted analyses, no consistent association was found between FMD quintiles and headache groups. CONCLUSIONS: There was no relationship between FMD and migraine or other headache diagnoses in this large cross-sectional study of otherwise healthy respondents including freedom from pulmonary and cardiovascular diseases. PMID- 26868819 TI - Paenibacillus baekrokdamisoli sp. nov., isolated from soil of crater lake. AB - A novel bacterial strain, Back-11T, was isolated from sediment soil of a crater lake, Baekrokdam, Hallasan, Jeju, Republic of Korea. Cells of strain Back-11T were Gram-stain-positive, motile, endospore-forming, rod-shaped and oxidase- and catalase-positive. It contained anteiso-C15 : 0 as the major fatty acid, menaquinone-7 (MK-7) as the predominant isoprenoid quinone, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and four unidentified aminophospholipids as the main polar lipids, and meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The DNA G+C content was 45.3 mol%. Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that strain Back-11T was most closely related to Paenibacillus taihuensis THMBG22T (95.5 % similarity) and fell into a clade in the genus Paenibacillus. On the basis of phylogenetic, chemotaxonomic and phenotypic data, strain Back-11T represents a novel species in the genus Paenibacillus, for which the name Paenibacillus baekrokdamisoli sp. nov. is proposed. The type strain is Back-11T ( = KCTC 33723T = CECT 8890T). PMID- 26868821 TI - Hypoxic conditions increases H2S-induced ER stress in A2870 cells. AB - Hypoxia - a state of lower oxygen demand-is responsible for a higher aggressiveness of tumors and therefore a worse prognosis. During hypoxia, several metabolic pathways are re-organized, e.g., energetic metabolism, modulation of pH, and calcium transport. Calcium is an important second messenger that regulates variety of processes in the cell. Thus, aim of this work was to compare H2S modulation of the intracellular calcium transport systems in hypoxia and in cells grown in standard culture conditions. For all experiments, we used ovarian cancer cell line (A2780). H2S is a novel gasotransmitter, known to be involved in a modulation of several calcium transport systems, thus resulting in altered calcium signaling. Two models of hypoxia were used in our study-chemical (induced by dimethyloxallyl glycine) and 2 % O2 hypoxia, both combined with a treatment using a slow H2S donor GYY4137. In hypoxia, we observed rapid changes in cytosolic and reticular calcium levels compared to cells grown in standard culture conditions, and these changes were even more exagerrated when combined with the GYY4137. Changes in a calcium homeostasis result from IP3 receptor's up regulation and down-regulation of the SERCA 2, which leads to a development of the endoplasmic reticulum stress. Based on our results, we propose a higher vulnerability of calcium transport systems to H2S regulation under hypoxia. PMID- 26868822 TI - Induction of hypoxia-inducible factor-1alpha by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis. AB - Alternations of environment signals such as neurotrophins may be the basis for malignant transformation of retinoblastoma (Rb), the most common primary intraocular malignancy in children. The aim of this study is to investigate the ability of brain-derived neurotrophic factor (BDNF) to decrease the chemosensitivity of Rb cells to the common chemotherapeutic agents and to explore the role of hypoxia-inducible factor-1alpha (HIF-1alpha) in such cellular process. The results showed that BDNF could induce higher expression of HIF 1alpha via activation of TrkB in human Y-79 retinoblastoma cells, which consequently contributed to its effect against chemotherapeutic agent-induced cytotoxicity and cell apoptosis. However, this protective effect could be potently reversed by knockdown of HIF-1alpha. Furthermore, BDNF strikingly prevented chemotherapeutic agent-induced alternations of apoptosis-related molecules, which could also be attenuated by silencing HIF-1alpha. Therefore, our findings demonstrated that BDNF could contribute to chemoresistance of Rb via modulation of HIF-1alpha expression, indicating that targeting at the BDNF TrkB/HIF-1alpha signaling pathway might be a promising strategy for the treatment of retinoblastoma in the future. PMID- 26868823 TI - [Macroscopic and functional anatomy of the apophyseal plate]. AB - Apophyses are growth zones attached to the shaft (corpus) of larger bones. They vary in size and develop their own ossification centres or form as part of an usually fibrocartilaginous tendon or ligament insertion. The structure of the cartilaginous apophyseal plate is very similar to that of an epiphyseal growth plate and like these they are adapted to withstand perpendicular compressive forces without becoming harmed. This is best highlighted by the fact that their mineralized borders always orient themselves perpendicular to the overall resulting force vector. The edges of the apophyseal plates are characteristically bent which allows them to resist moderate shear forces. Like the epiphyseal plates the apophyseal plates exhibit a zonal organization which is not very well adapted to permanently withstand shear forces, especially if they occur under dynamic conditions. In these situations the tendinous insertions with their collagen fibre anchoring system have to provide compensation when balancing the load transmitted across the system. PMID- 26868824 TI - Tyrosine kinase-mediated axial motility of basal cells revealed by intravital imaging. AB - Epithelial cells are generally considered to be static relative to their neighbours. Basal cells in pseudostratified epithelia display a single long cytoplasmic process that can cross the tight junction barrier to reach the lumen. Using in vivo microscopy to visualize the epididymis, a model system for the study of pseudostratified epithelia, we report here the surprising discovery that these basal cell projections--which we call axiopodia--periodically extend and retract over time. We found that axiopodia extensions and retractions follow an oscillatory pattern. This movement, which we refer to as periodic axial motility (PAM), is controlled by c-Src and MEK1/2-ERK1/2. Therapeutic inhibition of tyrosine kinase activity induces a retraction of these projections. Such unexpected cell motility may reflect a novel mechanism by which specialized epithelial cells sample the luminal environment. PMID- 26868825 TI - Full-field electroretinogram in autism spectrum disorder. AB - PURPOSE: To explore early findings that individuals with autism spectrum disorder (ASD) have reduced scotopic ERG b-wave amplitudes. METHODS: Light-adapted (LA) and dark-adapted (DA) ERGs were produced by a range of flash strengths that included and extended the ISCEV standard from two subject groups: a high functioning ASD group N = 11 and a Control group N = 15 for DA and N = 14 for LA ERGs who were matched for mean age and range. Flash strengths ranged from DA -4.0 to 2.3 log phot cd s m(-2) and LA -0.5 to 1.0 log phot cd s m(-2), and Naka Rushton curves were fitted to DA b-wave amplitude over the first growth limb ( 4.0 to -1.0 log phot cd s m(-2)). The derived parameters (V max, K m and n) were compared between groups. Scotopic 15-Hz flicker ERGs (14.93 Hz) were recorded to 10 flash strengths presented in ascending order from -3.0 to 0.5 log Td s to assess the slow and fast rod pathways, respectively. LA 30-Hz flicker ERGs, oscillatory potentials (OPs) and the responses to prolonged 120-ms ON-OFF stimuli were also recorded. RESULTS: The ISCEV LA b-wave amplitude produced by 0.5 log phot cd s m(-2) was lower in the ASD group (p < 0.001). Repeated measures ANOVA for the LA b-wave amplitude series forming the photopic hill was significantly (p = 0.01) different between groups. No group differences were observed for the distributions of the time to peaks of LA a-wave, b-wave or the photopic negative responses (phNR) (p > 0.08) to the single flash stimuli, but there was a significant difference in the distribution for the LA b-wave amplitudes (corrected p = 0.006). The prolonged 120-ms ON responses were smaller in the ASD group (corrected p = 0.003), but the OFF response amplitude (p > 0.6) and ON and OFF times to peaks (p > 0.4) were similar between groups. The LA OPs showed an earlier bifurcation of OP2 in the younger ASD participants; however, no other differences were apparent in the OPs or 30-Hz flicker waveforms. DA b-wave amplitudes fell below the control 5th centile of the controls for some individuals including four ASD participants (36 %) at the 1.5 log phot cd s m(-2) flash strength and two (18%) ASD participants at the lower -2 log phot cd s m(-2) flash strength. However, across the 13 flash strengths, there were no significant group differences for b-wave amplitude's growth (repeated measures ANOVA p = 0.83). Nor were there any significant differences between the groups for the Naka Rushton parameters (p > 0.09). No group differences were observed in the 15-Hz scotopic flicker phase or amplitude (p > 0.1), DA ERG a-wave amplitude or time to peak (p > 26). The DA b-wave time to peak at 0.5 log phot cd s m(-2) was longer in the ASD group (p = 0.04). CONCLUSION: Under LA conditions, the b-wave is reduced across the ASD group, along with the ON response of the prolonged flash ERG. Some ASD individuals also show subnormal DA ERG b-wave amplitudes. These exploratory findings suggest there is altered cone-ON bipolar signalling in ASD. PMID- 26868827 TI - [Design of the ORCA module in the OCEAN study : Evaluation of SD-OCT results in daily routine practice]. AB - BACKGROUND: The prevalence of blindness as defined by law could be reduced by the introduction of anti-vascular endothelial growth factor (VEGF) therapy. Because the treatment is governed by patient needs, mostly using morphological criteria, imaging diagnostics are of particular importance. The non-interventional OCEAN study investigates the treatment with ranibizumab in the clinical routine practice. In a subgroup of patients the interpretation of spectral domain optical coherence tomography (SD-OCT) scans by the treating physicians will be analyzed (ORCA module). METHODS: Over a period of 24 months data from patients with exudative age-related macular degeneration (AMD), macular edema due to retinal vein occlusion or diabetes mellitus, who are receiving intravitreal injections of ranibizumab, will be assessed. Information on examinations, visual acuity, treatment and recordings from imaging techniques will be documented using a questionnaire. The SD-OCT scans, fluorescence angiography and fundus photography will be independently analyzed by the ophthalmologist of the study center and by three reading centers (CIRCL Cologne, GRADE Bonn and M3 Munster). Automated measurements of retinal thickness by the manufacturers' software will be checked and if necessary manually corrected. A qualitative interpretation in terms of morphological criteria for (further) treatment will be performed. CONCLUSION: A thorough assessment of SD-OCT images during anti-VEGF therapy provides the basis for the best possible needs-oriented treatment regimen. The control of the quality of data from daily routine practice may indicate possible weaknesses allowing explicit training and therefore optimization of patient treatment. PMID- 26868826 TI - Bioresorbable scaffolds: a new paradigm in percutaneous coronary intervention. AB - Numerous advances and innovative therapies have been introduced in interventional cardiology over the recent years, since the first introduction of balloon angioplasty, but bioresorbable scaffold is certainly one of the most exciting and attracting one. Despite the fact that the metallic drug-eluting stents have significantly diminished the re-stenosis ratio, they have considerable limitations including the hypersensitivity reaction to the polymer that can cause local inflammation, the risk of neo-atherosclerotic lesion formation which can lead to late stent failure as well as the fact that they may preclude surgical revascularization and distort vessel physiology. Bioresorbable scaffolds overcome these limitations as they have the ability to dissolve after providing temporary scaffolding which safeguards vessel patency. In this article we review the recent developments in the field and provide an overview of the devices and the evidence that support their efficacy in the treatment of CAD. Currently 3 devices are CE marked and in clinical use. Additional 24 companies are developing these kind of coronary devices. Most frequently used material is PLLA followed by magnesium. PMID- 26868828 TI - [Treatment of corneal endothelial disorders by DMEK and UT-DSAEK. Indications, complications, results and follow-up]. AB - Various techniques for posterior lamellar keratoplasty have been established for the clinical routine and continuously improved during the last 15 years so that an extremely rapid recovery of vision is possible due to very thin transplants. Descemet membrane endothelial keratoplasty (DMEK) is the method of choice for simple corneal endothelial diseases and has already been applied in complex conditions of the anterior segment. The learning curve for DMEK is comparatively long and the risk of complications in complex anterior segment pathologies is higher than in Descemet's stripping automated endothelial keratoplasty (DSAEK); however, DMEK results in better visual outcome and less graft rejections than DSAEK. The latest evolution in posterior lamellar transplant surgery is ultrathin DSAEK (UT-DSAEK), where the grafted lamella is much thinner than in conventional DSAEK. Currently available data suggest that the resulting visual acuity after UT DSAEK is close to the visual acuity seen after DMEK; however, studies comparing the results after DMEK and UT-DSAEK are so far lacking. Whether the transplantation of these very thin DSAEK grafts also results in endothelial cell densities and graft rejection rates comparable to DMEK has to be proven. PMID- 26868829 TI - Group affiliation in self-management: support or threat to identity? AB - BACKGROUND: Self-management is considered important in chronic illness, and contemporary health policy recommends participation in support groups for individuals with chronic conditions. Although withdrawal from or non participation in support groups is an important problem, there is limited knowledge about individuals' own motivation for participation in or withdrawal from self-management support groups. OBJECTIVES: To investigate how individuals with type 2 diabetes perceive participation in group-based self-management support. DESIGN: This is a qualitative focus group study using a semi-structured interview guide. SETTING AND PARTICIPANTS: Sixteen participants diagnosed with type 2 diabetes were included in the study. Individuals with and without group affiliations were mixed in three focus groups to trigger discussions. In the analysis, reoccurring themes of engagement and discussions between participants were focused within a theoretical frame of institutional logic. The focus groups are seen as social spaces where participants construct identity. RESULTS: Both participation and non-participation in group-based self-management support are associated with dealing with the stigma of having type 2 diabetes. Negotiations contribute to constructing an illness dignity as a response to the logic of moral responsibility for the disease. DISCUSSION AND CONCLUSION: Contemporary policy contributes to societal understandings of individuals with type 2 diabetes as morally inadequate. Our study shows that group-based self-management support may counteract blame and contribute in negotiations of identity for individuals with type 2 diabetes. This mechanism makes participation in groups beneficial for some but stigma inducing for others. PMID- 26868830 TI - Detection of frailty in elderly cancer patients: Improvement of the G8 screening test. AB - OBJECTIVE: The G8 is a screening test to identify frail elderly patients with cancer. Objectives were to design and evaluate the performance of alternative tests taking into account other predictive domains for frailty. METHODS: We conducted a literature review to identify predictive factors of frailty. Using a Delphi consensus, we collected 24 European experts' opinions to validate the most relevant items to improve the G8. Alternative tests were created and performance assessed on a development population (ONCODAGE cohort). The highest performing test was compared to the G8, and validated through both an internal and an external population validation (Aquitaine Geriatric Oncology cohort). RESULTS: The study population consisted of 1435 patients (ONCODAGE cohort) and 364 patients (Aquitaine Geriatric Oncology cohort). Twenty-three experts validated two items with a strong consensus (>75%): modification of the threshold for the G8 polypharmacy item to six drugs per day and replacement of the G8 item on neuropsychological problems by four Instrumental Activities of Daily Living (IADL) items predictive of incident dementia, creating three modified G8 tests (addition of either item, or both). Only the G8 IADL-modified test had better performance than the G8 when tested on the ONCODAGE cohort: sensitivity=77%, specificity=67%. This test was validated on the internal (sensitivity=78%, specificity=71%) and external (sensitivity=88%, specificity=69%) validation populations. CONCLUSION: Adding the four IADL items improves the performance of the G8. We have developed and validated a G8-modified test that is more specific than the G8 to detect frail elderly, while still sensitive and feasible in less than 10 min. PMID- 26868831 TI - Thrombocytopaenia as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction. AB - BACKGROUND: Studies suggest that thrombocytopaenia is associated with a higher mortality in several diseases. Little is known about the effect of low platelet count on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to determine the prognostic value of thrombocytopaenia in these patients by assessing all-cause mortality. METHODS: A total of 1,907 patients with HFrEF, defined by left ventricular ejection fraction <40% on echocardiography, were analysed in this multi-centre retrospective study. All patients were on medical therapy with a beta-blocker and an angiotensin converting enzyme inhibitor. Patients were categorised into two groups based on platelet count measured within one month of the diagnosis of HFrEF: normal to mild thrombocytopaenia (platelet count 100,000-450,000 per uL); and moderate to severe thrombocytopaenia (platelet count <100,000 per uL). One-year all-cause mortality was compared between the two groups. RESULTS: Mean age was 65+/-15 years and 62% of patients were male. Overall one-year mortality was 17.2% with higher mortality among patients with HFrEF and moderate/severe thrombocytopaenia compared to those with normal/mild thrombocytopaenia (33.0% vs. 15.4%, p <0.001). After adjusting for baseline characteristics, patients with HFrEF and moderate/severe thrombocytopaenia had a higher mortality compared to patients with normal/mild thrombocytopaenia (HR 1.84, 95% CI 1.33-2.56, p <0.001). CONCLUSION: In patients with HFrEF, higher degree of thrombocytopaenia is associated with higher all-cause mortality. These findings may support the use of platelet counts as a prognostic marker in the assessment of the patient with HFrEF. PMID- 26868832 TI - The interplay among temperament, neuropsychological abilities, and global functioning in young hyperactive/inattentive children. AB - Cognition and emotion have been shown to interact and influence psychological functioning. However, to date these interactions have only been examined cross sectionally among inattentive and/or hyperactive/impulsive children. This study investigated the moderating effects of neuropsychological functioning at age 3-4 years on the relation between negative emotionality at age 3-4 years and global functioning 1 year later, at age 4-5 years. Hyperactive/inattentive (H/I; n = 114) preschoolers entered the study (BL: baseline) and were seen again 1 year later (F1). Children's BL scores on a neuropsychological test (NEPSY) and their temperament as rated by parents (Child Behavior Questionnaire) and teachers (Temperament Assessment Battery for Children-Revised) were obtained, as were clinicians' ratings of their global functioning (Children's Global Assessment Scale) at F1. Hierarchical linear regression analyses revealed that BL temperament variables accounted for significant variance in F1 Global Functioning. Significant interactions indicated that higher Verbal Executive abilities were associated with better child functioning when parent-rated Effortful Control was high, but not when Effortful Control was low. Additionally, high levels of Nonverbal Executive skills were associated with higher child global functioning when both parent- and teacher-rated negative affect was low, but not when negative affect was high. PMID- 26868820 TI - Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies. AB - BACKGROUND: Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers. METHODS: Subjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time. RESULTS: The decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large. CONCLUSIONS: The possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling. PMID- 26868833 TI - [Planned children--supporting and inhibiting influences on the development of personality and relationships after technology-assisted reproduction]. AB - In the western industrial countries more and more couples with an unfulfilled desire for a child use assisted reproductive technology (ART). This focusses on physical processes and doesn't sufficiently provide necessary supportive psychological/psychotherapeutic guidance.Neglecting the psychological dimension causes ART to enhance the risk for negative processes of emotional development of a child.After a brief overview of prevalence and summarizing the legal situation three areas will be discussed which involve a high risk potential and their influences on relationship- and personality development will be described: * The psychological burden for potential parents during the treatment. * Wishes of perfection and high expectations concerning the child which can turn normative crises into severe problems. * The frequent handling of the treatment as a taboo which can become a destructive family secret between parents and child.The paper will conclude with thoughts concerning prevention and treatment.Every person working in the field of childhood and adolescence can contribute to a healthy psychological development of these children. This means acknowledging and working through the emotional burden and the wishes and explaining about the dangers of taboos like in foster care and adoption. PMID- 26868834 TI - Quality of care and its determinants in longer term mental health facilities across Europe; a cross-sectional analysis. AB - BACKGROUND: The Quality Indicator for Rehabilitative Care (QuIRC) is an international, standardised quality tool for the evaluation of mental health facilities that provide longer term care. Completed by the service manager, it comprises 145 items that assess seven domains of care: living environment; treatments and interventions; therapeutic environment; self-management and autonomy; social interface; human rights; and recovery based practice. We used the QuIRC to investigate associations between characteristics of longer term mental health facilities across Europe and the quality of care they delivered to service patients. METHODS: QuIRC assessments were completed for 213 longer term mental health units in ten countries that were at various stages of deinstitutionalisation of their mental health services. Associations between QuIRC domain scores and unit descriptive variables were explored using simple and multiple linear regression that took into account clustering at the unit and country level. RESULTS: We found wide variation in QuIRC domain scores between individual units, but across countries, fewer than a quarter scored below 50 % on any domains. The quality of care was higher in units that were smaller, of mixed sex, that had a defined expected maximum length of stay and in which not all patients were severely disabled. CONCLUSIONS: This is the first time longer term mental health units across a number of European countries have been compared using a standardised measure. Further use of the QuIRC will allow greater understanding of the quality of care in these units across Europe and provide an opportunity to monitor pan-European quality standards of care for this vulnerable patient group. PMID- 26868836 TI - Subtropical Potential Vorticity Intrusion Drives Increasing Tropospheric Ozone over the Tropical Central Pacific. AB - Drawn from multiple reanalysis datasets, an increasing trend and westward shift in the number of Potential Vorticity intrusion events over the Pacific are evident. The increased frequency can be linked to a long-term trend in upper tropospheric equatorial westerly wind and subtropical jets during boreal winter to spring. These may be resulting from anomalous warming and cooling over the western Pacific warm pool and the tropical eastern Pacific, respectively. The intrusions brought dry and ozone rich air of stratospheric origin deep into the tropics. In the tropical upper troposphere, interannual ozone variability is mainly related to convection associated with El Nino/Southern Oscillation. Zonal mean stratospheric overturning circulation organizes the transport of ozone rich air poleward and downward to the high and midlatitudes leading there to higher ozone concentration. In addition to these well described mechanisms, we observe a long-term increasing trend in ozone flux over the northern hemispheric outer tropical (10-25 degrees N) central Pacific that results from equatorward transport and downward mixing from the midlatitude upper troposphere and lower stratosphere during PV intrusions. This increase in tropospheric ozone flux over the Pacific Ocean may affect the radiative processes and changes the budget of atmospheric hydroxyl radicals. PMID- 26868835 TI - Psychometric properties of the positive mental health instrument among people with mental disorders: a cross-sectional study. AB - BACKGROUND: The Positive Mental Health (PMH) instrument was developed and validated to assess the level of PMH and its six dimensions in a multi-ethnic general population sample. This cross-sectional study examines the psychometric properties of the instrument for assessing the level of PMH among help-seeking patients with mental disorders. METHODS: The PMH instrument was tested among 360 out-patients with schizophrenia, depression or anxiety spectrum disorders, seeking treatment at a tertiary psychiatric hospital and its affiliated clinics in Singapore. All participants completed the PMH instrument along with measures of life satisfaction, mental and overall health and happiness. Reliability (internal consistency), construct (Exploratory Structural Equation Modeling (ESEM)) and criterion (convergent and divergent) validity of the PMH instrument were tested in this population. Items were also tested for item response theory and differential item functioning (IRT-DIF). RESULTS: ESEM on the PMH instrument showed good fit with the model reflecting six factors (general coping, personal growth and autonomy, spirituality, interpersonal skills, emotional support, and global affect). Internal consistency was high (Cronbach's alpha >0.85) for the instrument and its six subscales. The PMH instrument fulfilled expected correlations with related constructs and demonstrated adequate item discrimination and difficulty estimates; however, significant DIF was noted for few items for age, gender and ethnicity groups. CONCLUSIONS: The PMH instrument is a reliable and valid instrument for measuring PMH dimensions in patients with mental disorders. Further studies in larger samples are needed to assess the impact of DIF on PMH scores. The implications for the shift in focus from just the negative aspects of mental disorders to including positive components in the assessment of patients with mental disorders are immense, and can be applied in routine mental health practice and policy making. PMID- 26868837 TI - What to Think About Antibiotic Prophylaxis and Infective Endocarditis. PMID- 26868838 TI - The Role of Regional Oxygen Saturation Using Near-Infrared Spectroscopy and Blood Lactate Levels as Early Predictors of Outcome After Pediatric Cardiac Surgery. AB - BACKGROUND: The purpose of the study was to evaluate the association between regional oxygen saturation (rSO2) desaturation score (calculated by multiplying the rSO2 < 50% by time in seconds the preoperative baseline value) measured with near-infrared spectroscopy and the peak of lactate with postoperative major morbidities in pediatric patients who undergo cardiac surgery. METHODS: We retrospectively analyzed the postoperative course of 152 patients between January 2012 and December 2013, for whom we continuously monitored cerebral rSO2 using near-infrared spectroscopy and serial arterial blood lactate levels for at least 48 hours. RESULTS: The median age at surgery was 128 days (interquartile range [IQR], 17-537 days). Thirty-nine patients had a single ventricle physiology (26%) and 135 patients (89%) required the use of cardiopulmonary bypass (median time of 130 minutes; IQR, 93-172 minutes). Median postoperative peak lactate level was 3 mmol/L (IQR, 2-5.3 mmol/L); 52 patients (34%) had a postoperative lactate level > 4.6 mmol/L. The median postoperative rSO2 desaturation score was 157 (IQR, 0 2050); 62 patients (41%) had an rSO2 desaturation score > 345. Fifty-seven patients (37%) had postoperative major morbidities. Using a multivariable regression model only rSO2 desaturation score > 345 was independently associated with major morbidities after surgery (odds ratio, 27.26; 95% confidence interval, 10.18-73.00). The proportion of patients with an rSO2 desaturation score > 345 within 240 minutes after surgery was higher than the rate of those who showed a peak of lactate > 4.6 mmol/L (84% vs 59%; P = 0.05). CONCLUSIONS: The postoperative rSO2 desaturation score has a stronger association with major postoperative morbidities than lactate and it also provides an earlier warning sign of hemodynamic or metabolic compromise. PMID- 26868839 TI - Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease. AB - Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. PMID- 26868840 TI - Infective Endocarditis Hospitalizations Before and After the 2007 American Heart Association Prophylaxis Guidelines. AB - BACKGROUND: In 2007, the American Heart Association (AHA) published revised guidelines for infective endocarditis (IE) prophylaxis. Population-based data with respect to the potential impact of these revised guidelines are lacking. METHODS: The Canadian Institute for Health Information Discharge Abstract Database was used to identify all hospitalizations between April 2002 and March 2013 having IE as a primary diagnosis. Hospitalization rates were determined using age-specific population data from Statistics Canada. Interrupted time series analysis was used to evaluate changes in the slope of hospitalization rates after the AHA guidelines were published. RESULTS: There were 9431 hospitalizations during the study period among 8055 patients (63% male patients). Time trend analysis showed an increase of 0.05 IE hospitalizations per 10 million population per month (95% confidence interval, 0.005-0.09; P = 0.029) from April 2002-March 2007 and an increase of 0.07 IE hospitalizations per 10 million population per month from April 2007-March 2013 (interaction P = 0.5213). Change point analysis showed that a change in the slope occurred in April 2011, 4 years after publication of the revised AHA guidelines. Staphylococcus aureus was the most commonly reported organism (29.4%). Streptococcal infections decreased over time, beginning before the 2007 guidelines (P < 0.0001). The presence of a pacemaker or defibrillator was an increasingly prevalent risk factor over time (4% increase per year; P = 0.0178). CONCLUSIONS: The rate of IE hospitalizations increased in Canada before and after the publication of the 2007 AHA guidelines, with no significant change in slope after 2007. These guidelines had no impact on the incidence of IE hospitalizations. PMID- 26868842 TI - The relationship between the sensation of incomplete voiding and a high postvoid residual volume. AB - BACKGROUND: Studies have shown that voiding symptoms do not correlate with a high postvoid residual volume. It is important to have clinical tools that help make early and effective decisions during the initial consultation. OBJECTIVE: To assess the validity and degree of concordance between the sensation of incomplete voiding and high postvoid residual volume. MATERIAL AND METHODS: Cross-sectional study of patients who underwent uroflowmetry (UFM) and postvoid residual volume (PVR) measurement due to lower urinary tract symptoms, with simultaneous scoring of International Prostate Symptom Score (IPSS), the International Consultation on Incontinence Questionnaire - Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) or Male Lower Urinary Tract Symptoms (ICIQ-MLUTS) during 2014-2015. We analysed the relationship between these data and the postvoid residual volume. RESULTS: The study included 303 patients, 75 (24.8%) of whom were women and 228 (75.2%) of whom were men. The mean age was 60.9 years (SD, 15.8), and the mean Qmax was 14.47mL/s (SD, 9.6). Sixty (19.8%) patients had a high PVR. We detected 240 (79.2%) patients with sensations of incomplete voiding (SIV), but its presence was not associated with a high PVR in the population. For the SIV, the sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios were 81.6%, 21.3%, 20.4%, 82.5%, 1.03 and 0.85, respectively. The area under the curve for the frequency of SIV was 0.52 (95%CI, 0.44-0.60, P=.5). The degree of concordance between SIV and high PVR was 0.014 (P=.6). In the ICIQ-MLUTS, PVR correlated with intermittence (Rho=0.132, P=.043) but not with SIV (Rho=0.09, P=.15). In the ICIQ-FLUTS, the frequency of urinary incontinence was positively correlated with PVR (Rho=0.216, P=.026). CONCLUSIONS: The sensation of incomplete voiding is not associated with a high postvoid residual volume. Other variables such as symptom severity, urinary effort and total score for voiding symptoms can be associated with a high residual urine volume. PMID- 26868841 TI - Selective inhibition of EZH2 by ZLD1039 blocks H3K27 methylation and leads to potent anti-tumor activity in breast cancer. AB - Enhancer of zeste homolog 2 (EZH2) is a candidate oncogenic driver due to its prevalent overexpression and aberrant repression of tumor suppressor genes in diverse cancers. Therefore, blocking EZH2 enzyme activity may present a valid therapeutic strategy for the treatment of cancers with EZH2 overexpression including breast cancers. Here, we described ZLD1039 a potent, highly selective, and orally bioavailable small molecule inhibitor of EZH2, which inhibited breast tumor growth and metastasis. ZLD1039 considerably inhibited EZH2 methyltransferase activity with nanomolar potency, decreased global histone-3 lysine-27 (H3K27) methylation, and reactivated silenced tumor suppressors connected to increased survival of patients with breast cancer. Comparable to conditional silencing of EZH2, its inhibition by ZLD1039 decreased cell proliferation, cell cycle arrest, and induced apoptosis. Comparably, treatment of xenograft-bearing mice with ZLD1039 led to tumor growth regression and metastasis inhibition. These data confirmed the dependency of breast cancer progression on EZH2 activity and the usefulness of ZLD1039 as a promising treatment for breast cancer. PMID- 26868843 TI - Artemia salina as a new index for assessment of acute cytotoxicity during co composting of sewage sludge and lignocellulose waste. AB - Considering the necessity to constantly monitor the safety of use of sewage sludge, we have focused on evaluating the toxicity of raw sludge and sludge treated by co-composting with date palm waste using an in vitro assessment of cytotoxicity based on Artemia salina larvae as a simple new sensitive and reliable routine test. The efficiency of co-composting in decreasing sludge toxicity was evaluated in terms of cytotoxicity abatement reaching 100% by the second month of composting for mixture A (1/3 sludge+2/3 date palm waste) and the third month for mixture B (1/2 sludge+1/2 date palm waste). Cytotoxicity abatement was confirmed by the increase of germination index, which reached over 100% with positive correlation for lettuce (R(2)=0.81 and 0.86) and for turnip (R(2)=0.87 and 0.74) for mixtures A and B respectively. A strong correlation between the proposed cytotoxicity test and the evolution of regulatory physical chemical approaches was found, (R(2)=0.88 and 0.89) for NH4(+)/NO3(-) and (R(2)=0.80 and 0.88) for C/N respectively for mixture A and B. These findings allow the inexpensive bioassay reported to be used as a highly sensitive test to determine the cytotoxicity and maturity of composts. PMID- 26868844 TI - Content-based image retrieval system for solid waste bin level detection and performance evaluation. AB - This paper presents a CBIR system to investigate the use of image retrieval with an extracted texture from the image of a bin to detect the bin level. Various similarity distances like Euclidean, Bhattacharyya, Chi-squared, Cosine, and EMD are used with the CBIR system for calculating and comparing the distance between a query image and the images in a database to obtain the highest performance. In this study, the performance metrics is based on two quantitative evaluation criteria. The first one is the average retrieval rate based on the precision recall graph and the second is the use of F1 measure which is the weighted harmonic mean of precision and recall. In case of feature extraction, texture is used as an image feature for bin level detection system. Various experiments are conducted with different features extraction techniques like Gabor wavelet filter, gray level co-occurrence matrix (GLCM), and gray level aura matrix (GLAM) to identify the level of the bin and its surrounding area. Intensive tests are conducted among 250 bin images to assess the accuracy of the proposed feature extraction techniques. The average retrieval rate is used to evaluate the performance of the retrieval system. The result shows that, the EMD distance achieved high accuracy and provides better performance than the other distances. PMID- 26868845 TI - Characterizing the variability of food waste quality: A need for efficient valorisation through anaerobic digestion. AB - In order to determine the variability of food waste (FW) characteristics and the influence of these variable values on the anaerobic digestion (AD) process, FW characteristics from 70 papers were compiled and analysed statistically. Results indicated that FW characteristics values are effectively very variable and that 24% of these variations may be explained by the geographical origin, the type of collection source and the season of the collection. Considering the whole range of values for physicochemical characteristics (especially volatile solids (VS), chemical oxygen demand (COD) and biomethane potential (BMP)), FW show good potential for AD treatment. However, the high carbohydrates contents (36.4%VS) and the low pH (5.1) might cause inhibitions by the rapid acidification of the digesters. As regards the variation of FW characteristics, FW categories were proposed. Moreover, the adequacy of FW characteristics with AD treatment was discussed. Four FW categories were identified with critical characteristics values for AD performance: (1) the high dry matter (DM) and total ammonia nitrogen (TAN) content of FW collected with green waste, (2) the high cellulose (CEL) content of FW from the organic fraction of municipal solid waste, (3) the low carbon-to-nitrogen (C/N) ratio of FW collected during summer, (4) the high value of TAN and Na of FW from Asia. For these cases, an aerobic pre-treatment or a corrective treatment seems to be advised to avoid instabilities along the digestion. Finally, the results of this review-paper provide a data basis of values for FW characteristics that could be used for AD process design and environmental assessment. PMID- 26868846 TI - Optimal management of substrates in anaerobic co-digestion: An ant colony algorithm approach. AB - Sewage sludge (SWS) is inevitably produced in urban wastewater treatment plants (WWTPs). The treatment of SWS on site at small WWTPs is not economical; therefore, the SWS is typically transported to an alternative SWS treatment center. There is increased interest in the use of anaerobic digestion (AnD) with co-digestion as an SWS treatment alternative. Although the availability of different co-substrates has been ignored in most of the previous studies, it is an essential issue for the optimization of AnD co-digestion. In a pioneering approach, this paper applies an Ant-Colony-Optimization (ACO) algorithm that maximizes the generation of biogas through AnD co-digestion in order to optimize the discharge of organic waste from different waste sources in real-time. An empirical application is developed based on a virtual case study that involves organic waste from urban WWTPs and agrifood activities. The results illustrate the dominate role of toxicity levels in selecting contributions to the AnD input. The methodology and case study proposed in this paper demonstrate the usefulness of the ACO approach in supporting a decision process that contributes to improving the sustainability of organic waste and SWS management. PMID- 26868847 TI - Evaluation of a new pulping technology for pre-treating source-separated organic household waste prior to anaerobic digestion. AB - A new technology for pre-treating source-separated organic household waste prior to anaerobic digestion was assessed, and its performance was compared to existing alternative pre-treatment technologies. This pre-treatment technology is based on waste pulping with water, using a specially developed screw mechanism. The pre treatment technology rejects more than 95% (wet weight) of non-biodegradable impurities in waste collected from households and generates biopulp ready for anaerobic digestion. Overall, 84-99% of biodegradable material (on a dry weight basis) in the waste was recovered in the biopulp. The biochemical methane potential for the biopulp was 469 +/- 7 mL CH4/g ash-free mass. Moreover, all Danish and European Union requirements regarding the content of hazardous substances in biomass intended for land application were fulfilled. Compared to other pre-treatment alternatives, the screw-pulping technology showed higher biodegradable material recovery, lower electricity consumption and comparable water consumption. The higher material recovery achieved with the technology was associated with greater transfer of nutrients (N and P), carbon (total and biogenic) but also heavy metals (except Pb) to the produced biomass. The data generated in this study could be used for the environmental assessment of the technology and thus help in selecting the best pre-treatment technology for source separated organic household waste. PMID- 26868848 TI - 13C Pathway Analysis for the Role of Formate in Electricity Generation by Shewanella Oneidensis MR-1 Using Lactate in Microbial Fuel Cells. AB - Microbial fuel cell (MFC) is a promising technology for direct electricity generation from organics by microorganisms. The type of electron donors fed into MFCs affects the electrical performance, and mechanistic understanding of such effects is important to optimize the MFC performance. In this study, we used a model organism in MFCs, Shewanella oneidensis MR-1, and (13)C pathway analysis to investigate the role of formate in electricity generation and the related microbial metabolism. Our results indicated a synergistic effect of formate and lactate on electricity generation, and extra formate addition on the original lactate resulted in more electrical output than using formate or lactate as a sole electron donor. Based on the (13)C tracer analysis, we discovered decoupled cell growth and electricity generation in S. oneidensis MR-1 during co utilization of lactate and formate (i.e., while the lactate was mainly metabolized to support the cell growth, the formate was oxidized to release electrons for higher electricity generation). To our best knowledge, this is the first time that (13)C tracer analysis was applied to study microbial metabolism in MFCs and it was demonstrated to be a valuable tool to understand the metabolic pathways affected by electron donors in the selected electrochemically-active microorganisms. PMID- 26868849 TI - Short-term chemical pretreatment cannot replace curettage in photodynamic therapy. AB - BACKGROUND: Guidelines for photodynamic therapy (PDT) recommend pretreatment with curettage/debulking to enhance intracellular formation of protoporphyrin IX (PpIX). However, studies suggest that new chemical pretreatment procedures may replace curettage/debulking. PURPOSE: To investigate how pretreatment with curettage and two combination ointments containing calcipotriol/betamethasone and salicylic acid/betamethasone affect PpIX fluorescence after the application of methyl aminolevulinate MAL and 5-aminolevulinic acid (BF-200 ALA). METHODS: Four fields on the forearms of 30 healthy volunteers were pretreated with curettage or short-term application of calcipotriol/betamethasone or salicylic acid/betamethasone for 20 min. Two fields were not pretreated, thus serving as reference. After pretreatment, MAL or BF-200 ALA was applied for 24 h, and PpIX fluorescence was measured hourly from 1 to 5 h and after 18, 21 and 24 h. RESULTS: Curettage significantly enhanced PpIX fluorescence for MAL from 1 to 21 h (P < 0.0041). For BF-200 ALA, curettage enhanced fluorescence from 1 to 5 h (P < 0.000064), while fluorescence was lower from 18 to 24 h. Pretreatment with salicylic acid/betamethasone and calcipotriol/betamethasone before BF-200 ALA application did not increase PpIX fluorescence from 1 to 5 h compared to no pretreatment, and both were significantly inferior to curettage (P < 0.0017 and 0.0024, respectively). CONCLUSION: Curettage significantly enhances PpIX fluorescence from 1 to 5 h and is superior to short-term chemical pretreatment. Our results support curettage as standard pretreatment in PDT. PMID- 26868850 TI - Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System. AB - PURPOSE: The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. METHODS: The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. RESULTS: In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% +/- 4.2% (from 276 +/- 57 to 182 +/- 38 cGy), corresponding to an extra sparing distance of 7.9 +/- 1.1 mm. The maximum sparing distance variation per patient is 1.4 +/- 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5 degrees , respectively, in all directions. CONCLUSIONS: The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer. PMID- 26868852 TI - [Acute pain therapy: no resting on our laurels]. PMID- 26868851 TI - miR-139 Functions as An Antioncomir to Repress Glioma Progression Through Targeting IGF-1 R, AMY-1, and PGC-1beta. AB - Gliomas are the most common primary malignant brain tumor with poor prognosis, characterized by a highly heterogeneous cell population, extensive proliferation, and migration. A lot of molecular mechanisms regulate gliomas development and invasion, including abnormal expression of oncogenes and variation of epigenetic modification. MicroRNAs could affect cell growth and functions. Several reports have demonstrated that miR-139 plays multifunctions in kinds of solid tumors through different pathways. However, the antitumor mechanisms of this miR-139 are not unveiled in detail. In this study, we not only validated the low expression level of miR-139 in glioma tissues and cell lines but also detected the effect of miR-139 on modulating gliomas proliferation and invasion both in vitro and in vivo. We identified insulin-like growth factor 1 receptor, associate of Myc 1, and peroxisome proliferator-activated receptor gamma coactivator 1beta as direct targets of miR-139 and the levels of them were all inversely correlated with miR 139 in gliomas. Insulin like growth factor 1 receptor promoted gliomas invasion through Akt signaling and increased proliferation in the peroxisome proliferator activated receptor gamma coactivator 1beta-dependent way. Associate of Myc 1 also facilitated gliomas progression by activating c-Myc pathway. Overexpression of the target genes could retrieve the antitumor function of miR-139, respectively, in different degrees. The nude mice transplantation tumor experiment displayed that glioma cells stably expressed miR-139 growth much slower in vivo than the negative control cells. Taken together, these findings suggested miR-139 acted as a favorable factor against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new evidenced prognostic marker and therapeutic target for gliomas. PMID- 26868853 TI - [How organized acute pain therapy in Germany began]. PMID- 26868854 TI - [Therapy recommendations in a pediatric outpatient pain clinic : Adherence and effectiveness of implementation]. AB - BACKGROUND: Supplementary pain-related recommendations for the treatment of chronic pain in children and adolescents are an essential component of multimodal pain treatment. Studies are scarce regarding adherence to these recommendations and their effectiveness. OBJECTIVE: The aim of this study was to evaluate patient adherence to pain-related recommendations and their effectiveness 12 months after initial presentation of children and adolescents with chronic pain to a pediatric outpatient pain clinic. MATERIALS AND METHODS: A total of 413 patients were assessed using a structured telephone interview. The assessment included pain characteristics during the last 4 weeks as well as information regarding the implementation of the pain-related recommendations and the effectiveness. Due to different recommendations given to migraine patients this subgroup was dealt with separately. RESULTS: Patients reported significant improvements 12 months after the initial presentation and 29.5 % of the patients were pain free. Adherence levels and estimated effectiveness regarding recommendations, such as change of lifestyle, multimodal inpatient treatment and use of medication were high. Other recommendations, such as active relaxation and outpatient psychotherapy had low adherence levels and low estimated effectiveness. Migraine patients had a significantly higher adherence rate and estimated effectiveness regarding the recommendation use of medication than non-migraine patients. CONCLUSION: The adherence level as well as the estimated effectiveness regarding the majority of pain-related recommendations was high. Some recommendations had low adherence rates and low estimated effectiveness. These results can help to further improve the performance of outpatient clinics for children and adolescents with chronic pain. PMID- 26868855 TI - Tightening slip knots in raw and degummed silk to increase toughness without losing strength. AB - Knots are fascinating topological elements, which can be found in both natural and artificial systems. While in most of the cases, knots cannot be loosened without breaking the strand where they are tightened, herein, attention is focused on slip or running knots, which on the contrary can be unfastened without compromising the structural integrity of their hosting material. Two different topologies are considered, involving opposite unfastening mechanisms, and their influence on the mechanical properties of natural fibers, as silkworm silk raw and degummed single fibers, is investigated and quantified. Slip knots with optimized shape and size result in a significant enhancement of fibers energy dissipation capability, up to 300-400%, without affecting their load bearing capacity. PMID- 26868856 TI - Erratum. PMID- 26868857 TI - Painful Violaceous Purpura on a 44-Year-Old Woman. PMID- 26868858 TI - Eyelid Swelling and Proptosis with Systemic Implications. PMID- 26868859 TI - A Rare Cause of Large Bowel Obstruction. PMID- 26868860 TI - Fabrication of Thickness-Controllable Micropatterned Polyelectrolyte Film/Nanoparticle Surfaces by Using the Plasma Oxidation Method. AB - We have demonstrated a novel way to form thickness-controllable polyelectrolyte film/nanoparticle patterns by using a plasma etching technique to form, first, a patterned self-assembled monolayer surface, followed by layer-by-layer assembly of polyelectrolyte-films/nanoparticles. Octadecyltrimethoxysilane (ODS) and (3 aminopropyl)triethoxysilane (APTES) self-assembled monolayers (SAMs) were used for polyelectrolyte-film and nanoparticle patterning, respectively. The resolution of the proposed patterning method can easily reach approximately 2.5 MUm. The height of the groove structure was tunable from approximately 2.5 to 150 nm. The suspended lipid membrane across the grooves was fabricated by incubating the patterned polyelectrolyte groove arrays in solutions of 1,2-dioleoyl-sn glycero-3-phosphocholine (DOPC) giant unilamellar vesicles (GUVs). The method demonstrated here reveals a new path to create patterned 2D or 3D structures. PMID- 26868861 TI - Post-Gastric Bypass Hypoglycemia. AB - Obesity is a major public health problem worldwide. Obesity-related illnesses, such as coronary heart disease, type 2 diabetes, hypertension, dyslipidemia, stroke, sleep apnea, and several forms of cancer (endometrial, breast, and colon), contribute to a significant number of deaths in the USA. Bariatric surgery, including the Roux-en-Y gastric bypass (RYGB) procedure, has demonstrated significant improvements in obesity and obesity-related co morbidities and is becoming more popular as the number of obese individuals rises. Despite the reported benefits of bariatric surgery, there are potential complications that physicians need to be aware of as the number of patients undergoing these procedures continues to increase. One challenging and potentially life-threatening complication that to date is not well understood is post-RYGB surgery hypoglycemia (PGBH). In this review, we will present the definition, historical perspective, diagnostic approach, currently available treatment options, and anecdotal assessment and treatment algorithm for this disorder. PMID- 26868862 TI - Alcohol use among Native Americans compared to whites: Examining the veracity of the 'Native American elevated alcohol consumption' belief. AB - BACKGROUND: This study uses national survey data to examine the veracity of the longstanding belief that, compared to whites, Native Americans (NA) have elevated alcohol consumption. METHODS: The primary data source was the National Survey on Drug Use and Health (NSDUH) from 2009 to 2013: whites (n=171,858) and NA (n=4,201). Analyses using logistic regression with demographic covariate adjustment were conducted to assess differences in the odds of NA and whites being alcohol abstinent, light/moderate drinkers (no binge/heavy consumption), binge drinkers (5+ drinks on an occasion 1-4 days), or heavy drinkers (5+ drinks on an occasion 5+ days) in the past month. Complementary alcohol abstinence, light/moderate drinking and excessive drinking analyses were conducted using Behavioral Risk Factor Surveillance System (BRFSS) data from 2011 to 2013: whites (n=1,130,658) and NA (n=21,589). RESULTS: In the NSDUH analyses, the majority of NA, 59.9% (95% CI: 56.7-63.1), abstained, whereas a minority of whites, 43.1% (CI: 42.6-43.6), abstained-adjusted odds ratio (AOR): 0.64 (CI: 0.56-0.73). Approximately 14.5% (CI: 12.0-17.4) of NA were light/moderate-only drinkers, versus 32.7% (CI: 32.2-33.2) of whites (AOR: 1.90; CI: 1.51-2.39). NA and white binge drinking estimates were similar-17.3% (CI: 15.0-19.8) and 16.7% (CI: 16.4 17.0), respectively (AOR: 1.00; CI: 0.83-1.20). The two populations' heavy drinking estimates were also similar-8.3% (CI: 6.7-10.2) and 7.5% (CI: 7.3-7.7), respectively (AOR: 1.06; CI: 0.85-1.32). Results from the BRFSS analyses generally corroborated those from NSDUH. CONCLUSIONS: In contrast to the 'Native American elevated alcohol consumption' belief, Native Americans compared to whites had lower or comparable rates across the range of alcohol measures examined. PMID- 26868863 TI - Binge drinking and subsequent depressive symptoms in young women in Australia. AB - BACKGROUND: The long-term impact of binge drinking on subsequent depressive symptoms is unclear. The aims were to identify longitudinal patterns of binge drinking and whether binge drinking preceded depressive symptoms in the short term (1-6 years) and long-term (10-15 years). METHODS: Longitudinal data from 1996, 2000 and 2009 mailed surveys of 8,197 women in the 1973-78 cohort of the Australian Longitudinal Study on Women's Health. Latent class analysis was used to identify binge drinking patterns and logistic regression to estimate associations with subsequent depressive symptoms. RESULTS: Five binge drinking trajectories were identified with predicted proportions of women who were very infrequent (24%), fluctuating infrequent (17%), frequent (17%), very frequent (26%) or extremely frequent binge drinkers (16%) between 16 and 21 years. At 22 27 years, depressive symptoms were significantly higher for extremely frequent binge drinkers (31% versus 21% in the short-term; 22% versus 16%-18% in the long term) than for less frequent bingers. Unadjusted odds of depressive symptoms were 1.70 (95%CI:1.38;2.08) times for extremely frequent binge drinkers than very infrequent bingers and were 1.30 (95%CI:1.04;1.63) after adjusting for demographics, relationships and experience of violence. At 31-36 years, the odds of depressive symptoms were 1.34 (95%CI:1.09-1.64) times for extremely frequent than very infrequent binge drinkers, but were not significant after adjusting for relationships and violence. CONCLUSIONS: Extremely frequent binge drinking (more than weekly) in late adolescence appears to elevate the risk of subsequent depressive symptoms in young women in their early twenties and thirties, emphasising the need for preventive strategies to curb binge drinking. PMID- 26868864 TI - MRI findings of spinal arteriovenous fistulas: focusing on localisation of fistulas and differentiation between spinal dural and perimedullary arteriovenous fistulas. AB - AIM: To investigate the magnetic resonance imaging (MRI) findings of spinal arteriovenous fistulas (AVFs) to predict their locations and types. MATERIALS AND METHODS: Patients who underwent spinal angiography for suspected spinal AVF between April 2003 and April 2013 were enrolled. Spine MRI images were analysed by two radiologists in consensus focusing on the distribution patterns of flow void pial vessels (FVPVs): longitudinal distribution pattern along the spinal level (even or uneven, with description of the most crowded level in uneven cases) and axial distribution pattern in relation to the cord (ventral, dorsal, or co-dominance). Spinal angiography served as the reference standard for the locations and types of fistulas. RESULTS: Thirty-two patients (M:F=24:8, mean age, 53 years; range, 2-74 years) were included. There were 18 patients with spinal dural AVFs (SDAVFs), seven with perimedullary AVFs, four with epidural AVFs, and three diagnosed as normal. In 12 of 15 longitudinally uneven AVFs, the most crowded levels of FVPVs corresponded to the true fistulous levels within two level differences. While dorsal dominance was predominant in SDAVFs (13/18), ventral dominance was predominant in perimedullary AVFs (5/7; p<0.01). CONCLUSION: Fistulous levels may be predicted to be within two levels of the most crowded levels of FVPVs. The dorsal dominance pattern of FVPVs favours SDAVFs, whereas ventral dominance suggests perimedullary AVFs. PMID- 26868865 TI - Screening and Treatment of Intestinal Rotational Abnormalities in Heterotaxy: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: To assess the role of screening and prophylactic surgery for intestinal rotational abnormalities (IRAs) in asymptomatic patients with heterotaxy. STUDY DESIGN: PubMed, Embase, and Cinahl were searched electronically to determine the overall incidence of IRAs in heterotaxy; the detection rate of IRAs associated with screening; the incidence of midgut volvulus in patients without screening; and the incidence of morbidity and mortality after prophylactic and emergency Ladd procedures. Relevant data were computed with a meta-analysis of proportions. Between-study heterogeneity was assessed with the I(2) statistic. RESULTS: From 276 papers identified, 24 studies with a total of 1433 patients with heterotaxy were included for systematic review. No randomized study was identified. True incidence of IRA in heterotaxy could not be ascertained through meta-analysis. In patients who underwent screening, the incidence of IRA was 58%. Acute midgut volvulus occurred in 5.8% of those who did not undergo screening. Postoperative mortality after Ladd procedure mainly was associated with cardiac insufficiency, and overall it was significantly greater in the emergency group compared with the prophylactic group (18% vs 5.6%). The complication rate also was greater in case of emergency vs prophylactic abdominal surgery (27% vs 16%); adhesional small bowel obstruction was the most common complication overall (6%). CONCLUSION: The screen-detected incidences of IRA and acute midgut volvulus were significantly greater in heterotaxy than the normal population. Prophylactic Ladd procedure was associated with less morbidity and mortality compared with emergency surgery. A long-term prospective randomized trial is needed to define the indication for screening and prophylactic treatment of IRA in heterotaxy. PMID- 26868866 TI - Cellulose conjugated FITC-labelled mesoporous silica nanoparticles: intracellular accumulation and stimuli responsive doxorubicin release. AB - Herein, we design novel cellulose conjugated mesoporous silica nanoparticle (CLS MSP) based nanotherapeutics for stimuli responsive intracellular doxorubicin (DOX) delivery. DOX molecules are entrapped in pores of the fabricated mesoporous silica nanoparticles (MSPs) while cellulose is used as an encapsulating material through esterification on the outlet of the pores of the MSPs to avoid premature DOX release under physiological conditions. In in vitro studies, stimuli responsive DOX release is successfully achieved from DOX loaded cellulose conjugated mesoporous silica nanoparticles (DOX/CLS-MSPs) by pH and cellulase triggers. Intracellular accumulation of DOX/CLS-MSPs in human liver cancer cells (HepG2 cells) is investigated through confocal microscope magnification. Cell viability of HepG2 cells is determined as the percentage of the cells incubated with DOX/CLS-MSPs compared with that of non-incubated cells through an MTT assay. PMID- 26868867 TI - The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation. AB - Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. PMID- 26868868 TI - Re: 'Hemothorax Management After Endovascular Treatment for Thoracic Aortic Rupture'. PMID- 26868869 TI - Re: 'Hemothorax Management After Endovascular Treatment For Thoracic Aortic Rupture'. PMID- 26868870 TI - Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats. AB - Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID- 26868872 TI - NSAIDs versus opioids and chest tube size in pleurodesis. PMID- 26868871 TI - Traffic-Related Air Pollution Contributes to Development of Facial Lentigines: Further Epidemiological Evidence from Caucasians and Asians. PMID- 26868873 TI - Metal-Free Oxidation of Primary Amines to Nitriles through Coupled Catalytic Cycles. AB - Synergism among several intertwined catalytic cycles allows for selective, room temperature oxidation of primary amines to the corresponding nitriles in 85-98% isolated yield. This metal-free, scalable, operationally simple method employs a catalytic quantity of 4-acetamido-TEMPO (ACT; TEMPO=2,2,6,6-tetramethylpiperidine N-oxide) radical and the inexpensive, environmentally benign triple salt oxone as the terminal oxidant under mild conditions. Simple filtration of the reaction mixture through silica gel affords pure nitrile products. PMID- 26868874 TI - RNA interference screening of interferon-stimulated genes with antiviral activities against classical swine fever virus using a reporter virus. AB - Classical swine fever (CSF) caused by classical swine fever virus (CSFV) is a highly contagious and often fatal disease of pigs, which leads to significant economic losses in many countries. Viral infection can induce the production of interferons (IFNs), giving rise to the transcription of hundreds of IFN stimulated genes (ISGs) to exert antiviral effects. Although numerous ISGs have been identified to possess antiviral activities against different viruses, rare anti-CSFV ISGs have been reported to date. In this study, to screen anti-CSFV ISGs, twenty-one ISGs reported previously were individually knocked down using small interfering RNAs (siRNAs) followed by infection with a reporter CSFV expressing Renilla luciferase (Rluc). As a result, four novel anti-CSFV ISGs were identified, including natural-resistance-associated macrophage protein 1 (NRAMP1), cytosolic 5'-nucleotidase III A (NT5C3A), chemokine C-X-C motif ligand 10 (CXCL10), and 2'-5'-oligoadenylate synthetase 1 (OAS1), which were further verified to exhibit antiviral activities against wild-type CSFV. We conclude that the reporter virus is a useful tool for efficient screening anti-CSFV ISGs. PMID- 26868876 TI - Density Functional Theory Modeling of Low-Loss Electron Energy-Loss Spectroscopy in Wurtzite III-Nitride Ternary Alloys. AB - In the present work, the dielectric response of III-nitride semiconductors is studied using density functional theory (DFT) band structure calculations. The aim of this study is to improve our understanding of the features in the low-loss electron energy-loss spectra of ternary alloys, but the results are also relevant to optical and UV spectroscopy results. In addition, the dependence of the most remarkable features with composition is tested, i.e. applying Vegard's law to band gap and plasmon energy. For this purpose, three wurtzite ternary alloys, from the combination of binaries AlN, GaN, and InN, were simulated through a wide compositional range (i.e., Al x Ga1-x N, In x Al1-x N, and In x Ga1-x N, with x=[0,1]). For this DFT calculations, the standard tools found in Wien2k software were used. In order to improve the band structure description of these semiconductor compounds, the modified Becke-Johnson exchange-correlation potential was also used. Results from these calculations are presented, including band structure, density of states, and complex dielectric function for the whole compositional range. Larger, closer to experimental values, band gap energies are predicted using the novel potential, when compared with standard generalized gradient approximation. Moreover, a detailed analysis of the collective excitation features in the dielectric response reveals their compositional dependence, which sometimes departs from a linear behavior (bowing). Finally, an advantageous method for measuring the plasmon energy dependence from these calculations is explained. PMID- 26868875 TI - Statins can exert dual, concentration dependent effects on HCV entry in vitro. AB - Statins are used daily by a large and increasing number of individuals worldwide. They were initially designed as 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) inhibitors to treat patients with hypercholesterolemia. Recent studies on HCV chronically infected individuals have suggested that their use in vivo in combination with PEG-IFN and ribavirin favor the sustained viral response (SVR). Herein, we describe the effects of a set of statins on HCV entry and on HCV key entry factors in vitro. Our results suggest that all tested statins exert a proviral effect through the upregulation of LDLR. Interestingly, at higher concentration, we also provide evidence of a yet unknown competing antiviral effect of statins (except for pravastatin) through the downregulation of CLDN-1. Importantly, this work enlightens the blunt proviral effect of pravastatin at the entry step of HCV in vitro. PMID- 26868877 TI - Editorial: Medical anthropology at home: Creating distance. PMID- 26868878 TI - The repatriation of anthropology: Some observations on Endo-ethnography. AB - For a few decades, anthropologists have increasingly turned to the study of their own society and culture. This article addresses the problems and the relative advantages and disadvantages of endogenous ethnography. It devotes special attention to the experiences of medical anthropologists who have conducted fieldwork at home. It is concluded that anthropology at home has no special epistemological position compared with anthropological research abroad, though there may be differences at the practical level of fieldwork and publishing. PMID- 26868879 TI - Anthropology at home via anthropology abroad: The problematic heritage. AB - Medical anthropology 'at home' owes an important debt to the methodological, epistemological, and theoretical research traditions developed by anthropologists working 'abroad'. One cannot deny this heritage. In turn, medical anthropology 'at home' has much to offer to social anthropology as a whole, since the field brings afresh gaze to familiar phenomena. By constructing new objects of research and new methods, and in particular through the effort of distancing-which is both more crucial and also harder to achieve at home than abroad-the study of medical anthropology in one's own society suggests new pathways towards the understanding of the individual in society. PMID- 26868880 TI - Strangers on terra cognita: Authors of the other in a mental hospitala. AB - Two important interrelated activities of medical anthropology at home are discussed: being at home in one's culture and the making of the Other. The author illustrates with ethnographic data from her fieldwork in a mental hospital how the anthropologist and the people in the hospital 'make' each other. Effects of this process are discussed. Making the other implies involvement in an arena in which morality and moral claims are contested and difference is constructed. This construction could serve uneven ends. Therefore, it is argued that making the other not only serves the construction of difference, but also sameness, understanding and bonding in human suffering. The process could serve as a bridge between psychiatric and anthropological practices if its written representations become part of the dialogue between the two disciplines and the informants. What are you writing? Are you writing down your findings? Fine! But do write about ME! (a woman from the hospital). Aber das Eigene soll ebenso gelernt werden wie das Fremde (Holderlin). PMID- 26868881 TI - Resonating to pain: Introspection as a tool in medical anthropology 'at home'. AB - The author has been involved in anthropological research on epilepsy in the setting of Swaziland and The Netherlands. This article explores the differences between those research experiences. It specifically describes an affective aspect of medical anthropological fieldwork at home: the idea that one's emotional response may alert to socio-cultural issues in a similar way to a psychotherapist's countertransference may alert to core issues. It is argued that finding a balance between distance and proximity is not only problematic on the level of cognition. Being 'at home' refers to the conceptional as well as emotional. PMID- 26868884 TI - Courses in medical anthropology: Switzerland. PMID- 26868882 TI - Locating difference: A medical anthropology 'at home'? AB - Although medical anthropologists have been doing research in Western societies for at least two decades, such research has only recently been labelled 'at home'. This paper investigates the usefulness of 'at home' as a programmatic concept for medical anthropology. Some of the developments regarding the heightened concern with Western societies and the prominent 'we-others' dualism in general social/cultural anthropology and medical anthropology since the beginning of the 1980s are outlined. By employing Henrietta Moore's ideas about 'difference between ' and 'difference within ', it is shown that 'at home ', as a relational term, gets its meanings in relation to its counterparts, most prominently 'abroad', and that it is based on the problematic 'we-others' dualism. The paper concludes that 'at home' is an unfavourable starting point for conceptualizing medical anthropological research in Western settings. Instead, in order to avoid the trap of reifying differences between 'we' and 'others', we rather need to take up positions of enquiry from which such categories can emerge as 'differences within '. PMID- 26868887 TI - Perception of light source distance from shading patterns. AB - Varying the distance of a light source from an object alters both the intensity and spatial distribution of surface shading patterns. We tested whether observers can use such cues to infer light source distance. Participants viewed stereoscopic renderings of rough objects with diffuse and glossy surfaces, which were illuminated by a point source at a range of distances. In one task, they adjusted the position of a small probe dot in three dimensions to report the apparent location of the light in the scene. In a second task, they adjusted the shading on one object (by moving an invisible light source) until it appeared to be illuminated from the same distance as another object. Participants' responses increased linearly with the true light source distance, suggesting that they have clear intuitions about how light source distance affects shading patterns for a variety of different surfaces. However, there were also systematic errors: Subjects overestimated light source distance in the probe adjustment task, and in both experiments, roughness and glossiness affected responses. We find the pattern of results is predicted surprisingly well by a simplistic model based only on the area of the image that exceeds a certain intensity threshold. Thus, although subjects can report light source distance, they may rely on simple- sometimes erroneous--heuristics to do so. PMID- 26868888 TI - Foveal and parafoveal contrast suppression are different: Mechanisms revealed by the study of healthy aging. AB - Visual contextual effects enable inference regarding neural mechanisms of cortical function, principally because of similarities between the stimulus properties influencing human perception and those modifying primate visual cortical neural responses. Most neurophysiology assesses nonfoveal cellular function and circuitry, while most human studies are foveal. Here we use parafoveal stimuli to measure center-surround perception of contrast in older and younger adults. We measure the influence of both near and far surround because neurophysiology demonstrates different circuitry for these areas. Contrast suppression from the near surround was reduced in older observers, while that from the far surround was intact. Our results are consistent with reduced intracortical inhibition with age and normal extrastriate feedback. Interestingly, in the same older observers, foveal surround suppression of contrast was strengthened relative to younger adults, demonstrating a clear distinction between foveal and parafoveal center-surround behavior. We assume that underlying alterations in cortical neurotransmitter levels with age should not differ substantially between the areas of visual cortex representing foveal and near foveal regions. Consequently, our results suggest regional differences in center-surround circuitry. That older adults have varied contextual effects of visual contrast as a function of retinal eccentricity suggests complex effects of aging on scene and object perception. PMID- 26868889 TI - Tilt representation beyond the retinotopic level. AB - We perceive a stable visual world, which enables successful interaction with our environment, despite movements of the eyes, head, and body. How are such perceptions formed? One possibility is that retino-centric visual input is transformed into representations at higher levels, such as head-, body-, or world centered representations. We investigated this hypothesis using the tilt aftereffect in a balanced adaptation paradigm designed to isolate head-, body-, and world-centered aftereffects. Observers adapted to two oppositely tilted stimuli, each contingent on one of two different gaze, head, or body directions. We found aftereffects contingent on gaze direction, but not head or body direction. This demonstrates that adaptable tilt representations exist in a head centric frame but not in higher reference frames. These aftereffects may be attributed to adaptation of retinotopic tilt-sensitive neurons whose responses are modulated by gaze direction (gain fields). Such neurons could support functionally head-centric tilt representations and are found as early as V1. On the basis of our results we would not expect activity in tilt-sensitive neurons to be modulated by head or body direction. The balanced adaptation paradigm is a useful tool for examining properties of the process responsible for gaze modulation of activity in visual neurons. PMID- 26868890 TI - Incorporation of non-canonical amino acids into proteins in yeast. AB - Non-canonical amino acids add extraordinary chemistries to proteins when they gain access to translation. In yeast, they can be incorporated into proteins by replacing a canonical amino acid or in a site-specific manner in response to an amber stop codon. The first approach simply exploits the natural substrate tolerance of the aminoacyl-tRNA synthetases in an auxotrophic host. The latter requires the co-expression of an orthogonal aminoacyl-tRNA synthetase that is specific for the non-canonical amino acid together with an amber suppressor tRNA. This review briefly recaps the residue- and site-specific incorporation techniques for non-canonical amino acids in yeast. It describes the selection system for orthogonal aminoacyl-tRNA synthetase/suppressor tRNA pairs and compares the different expression systems for these pairs. Numerous examples illustrate the application of non-canonical amino acids for protein engineering in yeast. The compilation includes the chemical structures of the amino acid analogs, the orthogonal pairs that were used for their incorporation and the titers of the labeled variant proteins. PMID- 26868891 TI - Rapidly Growing Vascular Mass Within the Thyroid. Angiosarcoma. PMID- 26868892 TI - Treatment strategies for early neurological deficits related to malpositioned pedicle screws in the lumbosacral canal: A pilot study. AB - OBJECTIVES: To employ a simple and fast method to evaluate those patients with neurological deficits and misplaced screws in relatively safe lumbosacral spine, and to determine if it is necessary to undertake revision surgery. METHODS: A total of 316 patients were treated by fixation of lumbar and lumbosacral transpedicle screws at our institution from January 2011 to December 2012. We designed the criteria for post-operative revision scores of pedicle screw malpositioning (PRSPSM) in the lumbosacral canal. We recommend the revision of the misplaced pedicle screw in patients with PRSPSM = 5' as early as possible. However, patients with PRSPSM < 5' need to follow the next consecutive assessment procedures. A total of 15 patients were included according to at least three stage follow-up. RESULTS: Five patients with neurological complications (PRSPSM = 5') underwent revision surgery at an early stage. The other ten patients with PRSPSM < 5' were treated by conservative methods for seven days. At three-month follow-up, only one patient showed delayed onset of neurological complications (PRSPSM 7') while refusing revision. Seven months later, PRSPSM decreased to 3' with complete rehabilitation. CONCLUSIONS: This study highlights the significance of consecutively dynamic assessments of PRSPSMs, which are unlike previous implementations based on purely anatomical assessment or early onset of neurological deficits.and also confirms our hypothesis that patients with early neurological complications may not need revision procedures in the relatively broad margin of the lumbosacral canal.Cite this article: X-J. Lin. Treatment strategies for early neurological deficits related to malpositioned pedicle screws in the lumbosacral canal: A pilot study. Bone Joint Res 2016;5:46-51. PMID- 26868893 TI - Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. AB - OBJECTIVES: T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. METHODS: In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. RESULTS: The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). CONCLUSIONS: Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure.Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52-60. doi: 10.1302/2046-3758.52.2000574. PMID- 26868894 TI - Fitness Field Tests' Correlation With Game Performance in U-19-Category Basketball Referees. AB - PURPOSE: To examine the relation between game performance, physiological responses, and field-test results in Tunisian basketball referees. METHODS: Computerized time-motion analysis, heart rate (HR), and blood lactate concentration [La-] were measured in 15 referees during 8 competitive games (under-19-y-old Tunisian league). Referees also performed a repeated-sprint test (RSA), Yo-Yo Intermittent Recovery Test level 1 (YYIRTL1), agility T-test, and 30 m sprint with 10-m lap time. Computerized video analysis determined the time spent in 5 locomotor activities (standing, walking, jogging, running, and sprint), then grouped in high-, moderate-, and low-intensity activities (HIAs, MIAs, and LIAs, respectively). RESULTS: YYIRTL1 performance correlated with (1) total distance covered during the 4th quarter (r = .52, P = .04) and (2) distance covered in LIA during all game periods (P < .05). Both distance covered and time spent in MIA during the 1st quarter were negatively correlated with the YYIRTL1 performance (r = -.53, P = .035; r = -.67, P = .004, respectively). A negative correlation was found between distance covered at HIA during the 2nd half (3rd quarter + 4th quarter) and fatigue index of the RSA test (r = -.54, P = .029). Mean HR (expressed as %HRpeak) during all game periods was correlated with YYIRTL1 performance (.61 <= r < .67, P < .01). CONCLUSIONS: This study showed that (1) the YYIRTL1 performance is a moderate predictor of game physical performance in U-19 basketball referees and (2) referees' RSA correlates with the amount of HIA performed during the 2nd half, which represents the ability to keep up with play. PMID- 26868895 TI - Physicochemical Properties of Microencapsulated omega-3 Salmon Oil with Egg White Powder. AB - The objective of this study was to produce microencapsulated omega(omega)-3 fatty acids (PUFAs) fortified egg white (EW) powders and to characterize their nutritional and physical properties. Stable emulsions (E-SO-EW) containing 3.43 (g/100 g) salmon oil (SO), 56.21 (g/100 g) EW, and 40.36 (g/100 g) water and a control (E-EW) containing EW and water were prepared. E-SO-EW and E-EW were separately spray dried at 130, 140, and 150 degrees C inlet air temperatures. This resulted in 3 microencapsulated SO fortified EW powders (SO-EW), and 3 dried EW powders (DEW). The powders were analyzed for microencapsulation efficiency (ME), color, fatty acids methyl esters, protein, fat, moisture, ash, amino acids, minerals, microstructure, and particle size. The EPA and DHA content of SO and the ME of the powders were not affected by the inlet air temperature. The crude protein content of SO-EW powders was approximately 24 (g/100 g) lower than dried EW powders. Leucine was the most abundant essential amino acid found in all the powders. Most of the powders' median particle size ranged from 15 to 30 MUm. The study demonstrated that microencapsulated omega-3 salmon oil with high quality EW protein can be produced by spray drying. PMID- 26868896 TI - Superficial and Deep Scapulothoracic Muscle Electromyographic Activity During Elevation Exercises in the Scapular Plane. AB - STUDY DESIGN: Controlled laboratory study. BACKGROUND: In scapular rehabilitation training, exercises that include a humeral elevation component in the scapular plane are commonly implemented. While performing humeral elevation, the scapula plays an important role, as it has to create a stable basis for the glenohumeral joint. However, a comparison of both deep and superficial muscle activity of the scapula between different types of elevation exercises is lacking and would be helpful for the clinician in choosing exercises. OBJECTIVES: To evaluate scapulothoracic muscle activity during different types of elevation exercises in the scapular plane. METHODS: Scapulothoracic muscle activity was measured in 21 healthy subjects, using fine-wire electromyography in the levator scapulae, pectoralis minor, and rhomboid major muscles and surface electromyography in the upper trapezius, middle trapezius, lower trapezius, and serratus anterior muscles. Measurements were conducted while the participants performed the following elevation tasks in the scapular plane: scaption (elevation in the scapular plane), towel wall slide, and elevation with external rotation (Thera Band). The exercises were performed without and with additional load. Possible differences between the exercises and the load were studied with a linear mixed model. RESULTS: Performing elevation in the scapular plane with an external rotation component resulted in higher middle trapezius and lower trapezius activity compared to the scaption and wall slide exercises. The upper trapezius was maximally activated during scaption. The pectoralis minor and serratus anterior showed the highest activity during the towel wall slide. The towel wall slide activated the retractors to a lesser degree (middle trapezius, lower trapezius, levator scapulae, rhomboid major). Adding load resulted in higher muscle activity in all muscles, with some muscles showing a different activation pattern between the elevation exercises, depending on the load condition. CONCLUSION: Scaption maximally activated the upper trapezius. The addition of an extra external-rotation component may be used when the goal is to activate the lower trapezius and middle trapezius. The towel wall slide exercise was found to increase pectoralis minor activity. Adding load resulted in higher muscle activity. Some muscles showed a different activation pattern between the elevation exercises, depending on the loading condition. The findings of this study give information about which elevation exercises a clinician can choose when the aim is to facilitate specific muscle scapulothoracic activity. PMID- 26868897 TI - Manual Therapy and Exercise for a Patient With Neck-Tongue Syndrome: A Case Report. AB - STUDY DESIGN: Case report. BACKGROUND: Neck-tongue syndrome (NTS) is defined as neck and/or head pain accompanied by ipsilateral dysesthesia of the tongue with sudden rotation of the head. Proposed causes include compression or irritation of the C2 nerve root as it courses behind the atlantoaxial joint or hypertrophy of the inferior oblique muscle. The primary purpose of this case report was to describe the conservative physical therapy treatment of a patient with uncomplicated NTS. CASE DESCRIPTION: The patient was a 13-year-old girl who reported insidious onset of sharp pain in the neck, numbness/tingling of the ipsilateral tongue/face, and tinnitus with cervical rotation. Symptoms occurred several times a week for approximately 10 seconds. Examination revealed impaired function, increased forward head posture, decreased cervical range of motion, and positive neurodynamic assessment. The patient's treatment included manual therapy and exercise for postural stabilization. OUTCOMES: Following 8 visits, pain of the neck and tongue numbness had resolved. Score on the Patient-Specific Functional Scale (PSFS), cervical range of motion, and posture had also improved. At the 22-month follow-up, infrequent, momentary symptoms in the neck and dysesthesia of the tongue were reported. The PSFS remained the same. Objective measures were normal. DISCUSSION: This case report describes the physical therapy management of an individual with NTS. The management strategy followed a protocol similar to that used for cervicogenic headaches, due to the involvement of the upper cervical spine with both NTS and cervicogenic headache and the lack of evidence for the treatment of NTS. Level of Evidence Therapy, level 4. PMID- 26868899 TI - Quantum dynamical investigation of the isotope effect in H2 formation on graphite at cold collision energies. AB - The Eley-Rideal abstraction of hydrogen atoms on graphitic surfaces at cold collision energies was investigated using a time-dependent wave packet method within the rigid-flat surface approximation, with a focus on hydrogen-deuterium isotopic substitutions. It is found that the marked isotope effect of collinear collisions disappears when the full dimensionality of the problem is taken into account, thereby suggesting that abstraction is less direct than commonly believed and proceeds through glancing rather than head-on collisions. In contrast, a clear isotope effect is observed for "hot-atom" formation, which appears to be strongly favored for heavy projectiles because of their higher density of physisorbed states. Overall, the dynamics is essentially classical and reasonably well described by quasi-classical trajectory methods at all but the lowest energies (?10 meV). A comparison of the results obtained in the (substrate) adiabatic and diabatic limits suggests that the reaction is only marginally affected by the lattice dynamics, but highlights the importance of including energy dissipation processes in order to accurately describe the internal excitation of the product molecules. PMID- 26868898 TI - Combined Effect of Free Nitrous Acid Pretreatment and Sodium Dodecylbenzene Sulfonate on Short-Chain Fatty Acid Production from Waste Activated Sludge. AB - Free nitrous acid (FNA) serving as a pretreatment is an effective approach to accelerate sludge disintegration. Also, sodium dodecylbenzene sulfonate (SDBS), a type of surfactants, has been determined at significant levels in sewage sludge, which thereby affects the characteristics of sludge. Both FNA pretreatment and sludge SDBS levels can affect short-chain fatty acid (SCFA) generation from sludge anaerobic fermentation. To date, however, the combined effect of FNA pretreatment and SDBS presence on SCFA production as well as the corresponding mechanisms have never been documented. This work therefore aims to provide such support. Experimental results showed that the combination of FNA and SDBS treatment not only improved SCFA accumulation but also shortened the fermentation time. The maximal SCFA accumulation of 334.5 mg chemical oxygen demand (COD)/g volatile suspended solids (VSS) was achieved at 1.54 mg FNA/L treatment and 0.02 g/g dry sludge, which was respectively 1.79-fold and 1.41-fold of that from FNA treatment and sludge containing SDBS alone. Mechanism investigations revealed that the combined FNA pretreatment and SDBS accelerated solubilization, hydrolysis, and acidification steps but inhibited the methanogenesis. All those observations were in agreement with SCFA enhancement. PMID- 26868900 TI - In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole. AB - Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 MUg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity(1), revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs. PMID- 26868901 TI - Phylogenetic analysis of dermatophyte species using DNA sequence polymorphism in calmodulin gene. AB - Use of phylogenetic species concepts based on rDNA internal transcribe spacer (ITS) regions have improved the taxonomy of dermatophyte species; however, confirmation and refinement using other genes are needed. Since the calmodulin gene has not been systematically used in dermatophyte taxonomy, we evaluated its intra- and interspecies sequence variation as well as its application in identification, phylogenetic analysis, and taxonomy of 202 strains of 29 dermatophyte species. A set of primers was designed and optimized to amplify the target followed by bilateral sequencing. Using pairwise nucleotide comparisons, a mean similarity of 81% was observed among 29 dermatophyte species, with inter species diversity ranging from 0 to 200 nucleotides (nt). Intraspecies nt differences were found within strains of Trichophyton interdigitale, Arthroderma simii, T. rubrum and A. vanbreuseghemii, while T. tonsurans, T. violaceum, Epidermophyton floccosum, Microsporum canis, M. audouinii, M. cookei, M. racemosum, M. gypseum, T. mentagrophytes, T schoenleinii, and A. benhamiae were conserved. Strains of E. floccosum/M. racemosum/M. cookei, A. obtosum/A. gertleri, T. tonsurans/T. equinum and a genotype of T. interdigitale had identical calmodulin sequences. For the majority of the species, tree topology obtained for calmodulin gene showed a congruence with coding and non-coding regions including ITS, BT2, and Tef-1alpha. Compared with the phylogenetic tree derived from ITS, BT2, and Tef-1alpha genes, some species such as E. floccosum and A. gertleri took relatively remote positions. Here, characterization and obtained dendrogram of calmodulin gene on a broad range of dermatophyte species provide a basis for further discovery of relationships between species. Studies of other loci are necessary to confirm the results. PMID- 26868902 TI - Antifungal activity of plant-derived essential oils on Candida tropicalis planktonic and biofilms cells. AB - Dental prosthesis supports Candida species growth and may predispose the oral cavity to lesions. C. tropicalis has emerged as a colonizer of prosthesis and has shown resistance to clinically used antifungal agents, which has increased the search for new antifungals. This work describes the effectiveness of fifteen essential oils (EOs) against C. tropicalis The EOs were obtained by hydrodistillation and were chemically characterized by gas chromatography-mass spectrometry. The antifungal activities of the EOs were evaluated by the microdilution method and showed that Pelargonium graveolens (Geraniaceae) (PG-EO) was the most effective oil. Geraniol and linalool were the major constituents of PG-EO. The 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5 Carboxanilide (XTT) assay showed that all the clinical C. tropicalis strains formed viable biofilms. Scanning electron microscopy examination of the biofilms revealed a complex architecture with basal layer of yeast cells and an upper layer of filamentous cells. Treatments with PG-EO, linalool, and geraniol significantly reduced the number of viable biofilm cells and inhibited biofilm formation after exposure for 48 h. PG-EO, geraniol, and linalool were not toxic to normal human lung fibroblasts (GM07492A) at the concentrations they were active against C. tropicalis Together, our results indicated that C. tropicalis is susceptible to treatment with PG-EO, geraniol, and linalool, which could become options to prevent or treat this infection. PMID- 26868903 TI - Biofilm production and antifungal susceptibility of co-cultured Malassezia pachydermatis and Candida parapsilosis isolated from canine seborrheic dermatitis. AB - The yeasts Malassezia (M.) pachydermatis and Candida (C.) parapsilosis are often co-isolated in case of canine seborrhea dermatitis (SD) and also are emerging as opportunistic pathogens of immunocompromised human beings. Increased information about how their relationship results in biofilm production and an antifungal response would be useful to inform treatment and control. This study was designed to investigate biofilm production derived from co-culture of M. pachydermatis and C. parapsilosis from dog skin and to determine their in vitro antifungal susceptibility. We demonstrated that regardless of yeast strain or origin all single and dual cultures produced biofilms within 24 hours, and the greatest amount was present after 72 hours. Biofilm production from mixed cultures was greater than for single strains (P < .05). All sessile forms of the single and dual cultures were resistant to the tested antifungals itraconazole and ketoconazole, whereas planktonic forms were susceptible. The study suggests that dual cultures produce stronger biofilms that are likely to enhance persistence in skin lesions in dogs and result in greater resistance to antifungal treatment. PMID- 26868904 TI - Antifungal susceptibility of invasive Candida bloodstream isolates from the Asia Pacific region. AB - Bloodstream infections caused by Candida species are of increasing importance and associated with significant mortality. We performed a multi-centre prospective observational study to identify the species and antifungal susceptibilities of invasive bloodstream isolates of Candida species in the Asia-Pacific region. The study was carried out over a two year period, involving 13 centers from Brunei, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. Identification of Candida species was performed at each study center, and reconfirmed at a central laboratory. Susceptibility testing was performed using a commercial broth dilution panel (Sensititre YeastOne YST-010, Thermofisher, United Kingdom) with susceptibility categorisation (S = susceptible, S-DD = susceptible dose-dependent) applied using breakpoints from the Clinical Laboratory Standards Institute. Eight hundred and sixty-one Candida isolates were included in the study. The most common species were C. albicans (35.9%), C. tropicalis (30.7%), C. parapsilosis (15.7%), and C. glabrata (13.6%). Non albicans species exceeded C. albicans species in centers from all countries except Taiwan. Fluconazole susceptibility was almost universal for C. albicans (S = 99.7%) but lower for C. tropicalis (S = 75.8%, S-DD = 6.1%), C. glabrata (S-DD = 94.9%), and C. parapsilosis (S = 94.8%). Echinocandins demonstrated high rates of in vitro susceptibility (S>99%) against C. albicans, C. tropicalis, and C. parapsilosis This study demonstrates that non-albicans species are the most common isolates from bloodstream infections in most countries in the Asia-Pacific region, with C. tropicalis as the predominant species. Because of the prevalence of reduced susceptibility to fluconazole in non-albicans species, the study indicates that echinocandins should be the antifungal of choice in clinically unstable or high-risk patients with documented candidemia. PMID- 26868905 TI - Posaconazole oral suspension primary prophylaxis in acute leukemia and allogeneic stem cell transplant patients: can it be used without measurement of plasma concentration? AB - Posaconazole oral suspension (PCZ-susp) can display a variable degree of inter and intra-individual absorption. However, there is no agreement on the need of plasma-posaconazole-concentration (PPC) monitoring as a routine practice in patients receiving PCZ-susp. In this prospective, multicenter study we evaluated the variability of PPCs in hematologic patients receiving PCZ-susp prophylaxis with the aim to define conditions at different risk of subtherapeutic PPCs. Overall, 103 acute leukemia (AL) patients submitted to intensive chemotherapy (115 courses) and 46 allogeneic stem cell transplant (allo-SCT) recipients (47 courses) receiving PCZ-susp prophylaxis were considered. The adequacy of PPC pattern after the steady state (>=day 7 of treatment) in courses with two or more PPC measurements was defined as follows: inadequate pattern: PPC < 0.5 mcg/ml at least once; borderline pattern: PPC always >=0.5mcg/ml but < 0.7 mcg/ml at least once; adequate pattern: PPC always >=0.7 mcg/ml. The PPC pattern was evaluable in 83 and 37 AL and allo-SCT patients, respectively. It was adequate, borderline and inadequate in 63.9%, 14.5%, and 21.7% of courses, respectively, in AL, and in 62.2%, 10.8%, and 27.0% of courses, respectively, in allo-SCT. In both groups, an inadequate PPC pattern was associated with the development of diarrhea. In absence of diarrhea, the probability of an inadequate PPC pattern was 11.9% in AL and 17.2% in allo-SCT patients. PCZ-susp might be used without stringent need of PPC monitoring in patients without diarrhea. PMID- 26868906 TI - Application of imaging mass spectrometry for the molecular diagnosis of human breast tumors. AB - Distinguishing breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS) is a key step in breast surgery, especially to determine whether DCIS is associated with tumor cell micro-invasion. However, there is currently no reliable method to obtain molecular information for breast tumor analysis during surgery. Here, we present a novel air flow-assisted ionization (AFAI) mass spectrometry imaging method that can be used in ambient environments to differentiate breast cancer by analyzing lipids. In this study, we demonstrate that various subtypes and histological grades of IDC and DCIS can be discriminated using AFAI-MSI: phospholipids were more abundant in IDC than in DCIS, whereas fatty acids were more abundant in DCIS than in IDC. The classification of specimens in the subtype and grade validation sets showed 100% and 78.6% agreement with the histopathological diagnosis, respectively. Our work shows the rapid classification of breast cancer utilizing AFAI-MSI. This work suggests that this method could be developed to provide surgeons with nearly real time information to guide surgical resections. PMID- 26868908 TI - A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity. AB - Vorinostat is an FDA-approved histone deacetylase inhibitor (HDACi) that has proven clinical success in some patients; however, it remains unclear why certain patients remain unresponsive to this agent and other HDACis. Constitutive STAT (signal transducer and activator of transcription) activation, overexpression of prosurvival Bcl-2 proteins and loss of HR23B have been identified as potential biomarkers of HDACi resistance; however, none have yet been used to aid the clinical utility of HDACi. Herein, we aimed to further elucidate vorinostat resistance mechanisms through a functional genomics screen to identify novel genes that when knocked down by RNA interference (RNAi) sensitized cells to vorinostat-induced apoptosis. A synthetic lethal functional screen using a whole genome protein-coding RNAi library was used to identify genes that when knocked down cooperated with vorinostat to induce tumor cell apoptosis in otherwise resistant cells. Through iterative screening, we identified 10 vorinostat resistance candidate genes that sensitized specifically to vorinostat. One of these vorinostat-resistance genes was GLI1, an oncogene not previously known to regulate the activity of HDACi. Treatment of vorinostat-resistant cells with the GLI1 small-molecule inhibitor, GANT61, phenocopied the effect of GLI1 knockdown. The mechanism by which GLI1 loss of function sensitized tumor cells to vorinostat induced apoptosis is at least in part through interactions with vorinostat to alter gene expression in a manner that favored apoptosis. Upon GLI1 knockdown and vorinostat treatment, BCL2L1 expression was repressed and overexpression of BCL2L1 inhibited GLI1-knockdown-mediated vorinostat sensitization. Taken together, we present the identification and characterization of GLI1 as a new HDACi resistance gene, providing a strong rationale for development of GLI1 inhibitors for clinical use in combination with HDACi therapy. PMID- 26868909 TI - Transcription factor C/EBP-beta induces tumor-suppressor phosphatase PHLPP2 through repression of the miR-17-92 cluster in differentiating AML cells. AB - PHLPP2, a member of the PH-domain leucine-rich repeat protein phosphatase (PHLPP) family, which targets oncogenic kinases, has been actively investigated as a tumor suppressor in solid tumors. Little is known, however, regarding its regulation in hematological malignancies. We observed that PHLPP2 protein expression, but not its mRNA, was suppressed in late differentiation stage acute myeloid leukemia (AML) subtypes. MicroRNAs (miR or miRNAs) from the miR-17-92 cluster, oncomir-1, were shown to inhibit PHLPP2 expression and these miRNAs were highly expressed in AML cells that lacked PHLPP2 protein. Studies showed that miR 17-92 cluster regulation was, surprisingly, independent of transcription factors c-MYC and E2F in these cells; instead all-trans-retinoic acid (ATRA), a drug used for terminally differentiating AML subtypes, markedly suppressed miR-17-92 expression and increased PHLPP2 protein levels and phosphatase activity. Finally, we demonstrate that the effect of ATRA on miR-17-92 expression is mediated through its target, transcription factor C/EBPbeta, which interacts with the intronic promoter of the miR-17-92 gene to inhibit transactivation of the cluster. These studies reveal a novel mechanism for upregulation of the phosphatase activity of PHLPP2 through C/EBPbeta-mediated repression of the miR 17-92 cluster in terminally differentiating myeloid cells. PMID- 26868910 TI - Evolutionary divergence of the necroptosis effector MLKL. AB - The pseudokinase, MLKL (mixed-lineage kinase domain-like), is the most terminal obligatory component of the necroptosis cell death pathway known. Phosphorylation of the MLKL pseudokinase domain by the protein kinase, receptor interacting protein kinase-3 (RIPK3), is known to be the key step in MLKL activation. This phosphorylation event is believed to trigger a molecular switch, leading to exposure of the N-terminal four-helix bundle (4HB) domain of MLKL, its oligomerization, membrane translocation and ultimately cell death. To examine how well this process is evolutionarily conserved, we analysed the function of MLKL orthologues. Surprisingly, and unlike their mouse, horse and frog counterparts, human, chicken and stickleback 4HB domains were unable to induce cell death when expressed in murine fibroblasts. Forced dimerization of the human MLKL 4HB domain overcame this defect and triggered cell death in human and mouse cell lines. Furthermore, recombinant proteins from mouse, frog, human and chicken MLKL, all of which contained a 4HB domain, permeabilized liposomes, and were most effective on those designed to mimic plasma membrane composition. These studies demonstrate that the membrane-permeabilization function of the 4HB domain is evolutionarily conserved, but reveal that execution of necroptotic death by it relies on additional factors that are poorly conserved even among closely related species. PMID- 26868907 TI - Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? AB - Mesenchymal stem cells (MSCs), a non-hematopoietic stem cell population first discovered in bone marrow, are multipotent cells capable of differentiating into mature cells of several mesenchymal tissues, such as fat and bone. As common progenitor cells of adipocytes and osteoblasts, MSCs are delicately balanced for their differentiation commitment. Numerous in vitro investigations have demonstrated that fat-induction factors inhibit osteogenesis, and, conversely, bone-induction factors hinder adipogenesis. In fact, a variety of external cues contribute to the delicate balance of adipo-osteogenic differentiation of MSCs, including chemical, physical, and biological factors. These factors trigger different signaling pathways and activate various transcription factors that guide MSCs to commit to either lineage. The dysregulation of the adipo-osteogenic balance has been linked to several pathophysiologic processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. Thus, the regulation of MSC differentiation has increasingly attracted great attention in recent years. Here, we review external factors and their signaling processes dictating the reciprocal regulation between adipocytes and osteoblasts during MSC differentiation and the ultimate control of the adipo-osteogenic balance. PMID- 26868911 TI - Deadly dowry: how engulfment pathways promote cell killing. PMID- 26868914 TI - Emotional Consequences of Finasteride: Fool's Gold. AB - Androgenetic alopecia, the gradual, progressive loss of hair frequently results in psychological despair, in part related to changes in self-image. Current androgenetic alopecia treatments are limited to hair transplantation and medications that inhibit dihydrotestosterone, a potent androgen associated with follicular micronization. Users of finasteride, which prevents dihydrotestosterone production, report serious physical and emotional adverse effects, collectively known as post-finasteride syndrome. Psychiatric illnesses and personality traits, specifically neuroticism influence emotional well-being. Limited research exists exploring the psychological corollaries of post finasteride syndrome and preexisting Axis I and Axis II mental health conditions. The aim of this study was to explore how having a preexisting personal and/or familial history of a psychiatric diagnosis and certain personality traits may influence anxiety and depression among finasteride users. Participants in this online survey completed the Beck Depression Inventory, the Beck Anxiety Inventory, and Ten-Item Personality Inventory. An important finding in this study was that almost 57% ( n = 97) of men reported a psychiatric diagnosis and 28% ( n = 27) had a first-degree relative with a mental health disorder, of this group 17 only had a family history. Nearly 50% of the men surveyed reported clinically significant depression as evidenced by Beck Depression Inventory score and 34% experienced anxiety on the Beck Anxiety Inventory. There were no statistically significant trends in personality traits reported. Results provide evidence on the need to screen for psychiatric history and counseling patients about the potential psychological consequences of finasteride. Prescribing clinicians should carefully weigh the risk/benefit ratio with these patients. PMID- 26868913 TI - Inflammasome-dependent IL-1beta release depends upon membrane permeabilisation. AB - Interleukin-1beta (IL-1beta) is a critical regulator of the inflammatory response. IL-1beta is not secreted through the conventional ER-Golgi route of protein secretion, and to date its mechanism of release has been unknown. Crucially, its secretion depends upon the processing of a precursor form following the activation of the multimolecular inflammasome complex. Using a novel and reversible pharmacological inhibitor of the IL-1beta release process, in combination with biochemical, biophysical, and real-time single-cell confocal microscopy with macrophage cells expressing Venus-labelled IL-1beta, we have discovered that the secretion of IL-1beta after inflammasome activation requires membrane permeabilisation, and occurs in parallel with the death of the secreting cell. Thus, in macrophages the release of IL-1beta in response to inflammasome activation appears to be a secretory process independent of nonspecific leakage of proteins during cell death. The mechanism of membrane permeabilisation leading to IL-1beta release is distinct from the unconventional secretory mechanism employed by its structural homologues fibroblast growth factor 2 (FGF2) or IL 1alpha, a process that involves the formation of membrane pores but does not result in cell death. These discoveries reveal key processes at the initiation of an inflammatory response and deliver new insights into the mechanisms of protein release. PMID- 26868912 TI - Cell death, clearance and immunity in the skeletal muscle. AB - The skeletal muscle is an immunologically unique tissue. Leukocytes, virtually absent in physiological conditions, are quickly recruited into the tissue upon injury and persist during regeneration. Apoptosis, necrosis and autophagy coexist in the injured/regenerating muscles, including those of patients with neuromuscular disorders, such as inflammatory myopathies, dystrophies, metabolic and mitochondrial myopathies and drug-induced myopathies. Macrophages are able to alter their function in response to microenvironment conditions and as a consequence coordinate changes within the tissue from the early injury throughout regeneration and eventual healing, and regulate the activation and the function of stem cells. Early after injury, classically activated macrophages ('M1') dominate the picture. Alternatively activated M2 macrophages predominate during resolution phases and regulate the termination of the inflammatory responses. The dynamic M1/M2 transition is increasingly felt to be the key to the homeostasis of the muscle. Recognition and clearance of debris originating from damaged myofibers and from dying stem/progenitor cells, stromal cells and leukocytes are fundamental actions of macrophages. Clearance of apoptotic cells and M1/M2 transition are causally connected and represent limiting steps for muscle healing. The accumulation of apoptotic cells, which reflects their defective clearance, has been demonstrated in various tissues to prompt autoimmunity against intracellular autoantigens. In the muscle, in the presence of type I interferon, apoptotic myoblasts indeed cause the production of autoantibodies, lymphocyte infiltration and continuous cycles of muscle injury and regeneration, mimicking human inflammatory myopathies. The clearance of apoptotic cells thus modulates the homeostatic response of the skeletal muscle to injury. Conversely, defects in the process may have deleterious local effects, guiding maladaptive tissue remodeling with collagen and fat accumulation and promoting autoimmunity itself. There is strong promise for novel treatments based on new knowledge of cell death, clearance and immunity in the muscle. PMID- 26868917 TI - Examining the Relationship Between Past Orientation and US Suicide Rates: An Analysis Using Big Data-Driven Google Search Queries. AB - BACKGROUND: Internet search query data reflect the attitudes of the users, using which we can measure the past orientation to commit suicide. Examinations of past orientation often highlight certain predispositions of attitude, many of which can be suicide risk factors. OBJECTIVE: To investigate the relationship between past orientation and suicide rate by examining Google search queries. METHODS: We measured the past orientation using Google search query data by comparing the search volumes of the past year and those of the future year, across the 50 US states and the District of Columbia during the period from 2004 to 2012. We constructed a panel dataset with independent variables as control variables; we then undertook an analysis using multiple ordinary least squares regression and methods that leverage the Akaike information criterion and the Bayesian information criterion. RESULTS: It was found that past orientation had a positive relationship with the suicide rate (P <= .001) and that it improves the goodness of-fit of the model regarding the suicide rate. Unemployment rate (P <= .001 in Models 3 and 4), Gini coefficient (P <= .001), and population growth rate (P <= .001) had a positive relationship with the suicide rate, whereas the gross state product (P <= .001) showed a negative relationship with the suicide rate. CONCLUSIONS: We empirically identified the positive relationship between the suicide rate and past orientation, which was measured by big data-driven Google search query. PMID- 26868916 TI - Structural semiconductor-to-semimetal phase transition in two-dimensional materials induced by electrostatic gating. AB - Dynamic control of conductivity and optical properties via atomic structure changes is of technological importance in information storage. Energy consumption considerations provide a driving force towards employing thin materials in devices. Monolayer transition metal dichalcogenides are nearly atomically thin materials that can exist in multiple crystal structures, each with distinct electrical properties. By developing new density functional-based methods, we discover that electrostatic gating device configurations have the potential to drive structural semiconductor-to-semimetal phase transitions in some monolayer transition metal dichalcogenides. Here we show that the semiconductor-to semimetal phase transition in monolayer MoTe2 can be driven by a gate voltage of several volts with appropriate choice of dielectric. We find that the transition gate voltage can be reduced arbitrarily by alloying, for example, for Mo(x)W(1 x)Te2 monolayers. Our findings identify a new physical mechanism, not existing in bulk materials, to dynamically control structural phase transitions in two dimensional materials, enabling potential applications in phase-change electronic devices. PMID- 26868915 TI - Merida virus, a putative novel rhabdovirus discovered in Culex and Ochlerotatus spp. mosquitoes in the Yucatan Peninsula of Mexico. AB - Sequences corresponding to a putative, novel rhabdovirus [designated Merida virus (MERDV)] were initially detected in a pool of Culex quinquefasciatus collected in the Yucatan Peninsula of Mexico. The entire genome was sequenced, revealing 11 798 nt and five major ORFs, which encode the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA polymerase (L). The deduced amino acid sequences of the N, G and L proteins have no more than 24, 38 and 43 % identity, respectively, to the corresponding sequences of all other known rhabdoviruses, whereas those of the P and M proteins have no significant identity with any sequences in GenBank and their identity is only suggested based on their genome position. Using specific reverse transcription-PCR assays established from the genome sequence, 27 571 C. quinquefasciatus which had been sorted in 728 pools were screened to assess the prevalence of MERDV in nature and 25 pools were found positive. The minimal infection rate (calculated as the number of positive mosquito pools per 1000 mosquitoes tested) was 0.9, and similar for both females and males. Screening another 140 pools of 5484 mosquitoes belonging to four other genera identified positive pools of Ochlerotatus spp. mosquitoes, indicating that the host range is not restricted to C. quinquefasciatus. Attempts to isolate MERDV in C6/36 and Vero cells were unsuccessful. In summary, we provide evidence that a previously undescribed rhabdovirus occurs in mosquitoes in Mexico. PMID- 26868918 TI - Complicated abdominal pregnancy with placenta feeding off sacral plexus and subsequent multiple ectopic pregnancies during a 4-year follow-up: a case report. AB - BACKGROUND: Abdominal pregnancy (pregnancy in the peritoneal cavity) is a very rare and serious type of extrauterine gestation that accounts for approximately 1.4% of all ectopic pregnancies. It also represents one of the few times an ectopic pregnancy can be carried to term. Early strategic diagnosis and management decisions can make a critical difference with regards to severity of morbidity and mortality risk. After an extensive search of the English language medical literature, we are unaware of any case of abdominal pregnancy in which the placenta was receiving its vascular supply from the sacral plexus. CASE PRESENTATION: A 26-year-old African-American woman, primigravida, at 16 weeks 4 days' gestation, presented to our Emergency Department with abdominal pain. She did not complain of any vaginal bleeding. A physical examination revealed mild abdominal tenderness and no blood in the vaginal vault. Laboratory findings corresponded to an increased level of beta human chorionic gonadotropin; magnetic resonance imaging confirmed an abdominal pregnancy. She underwent feticide, administration of methotrexate and a laparotomy was done which was immediately deferred due to perceived increased bleeding risk. She was found to have an intra abdominal ectopic pregnancy with the placenta attached to her omentum, cul-de-sac and rectosigmoid, with unusual and extensive vascularity from the sacral plexus. A repeat laparotomy was performed 11 weeks later, aimed at removal of the gestational sac and placenta that were left in situ on the first laparotomy. This time, we achieved successful removal of the peritoneal gestation, lysis of adhesions, ligation of vascular supply and cautery of the diminished vasculature. Subsequently, she had two ectopic pregnancies, which were managed with both medical and surgical interventions. CONCLUSIONS: Ectopic pregnancies should be identified early and evaluated for the etiology of the presentation. Rarely, an ectopic pregnancy implants at an extratubal location. Today, early intervention saves lives and reduces morbidity, but ectopic pregnancy still accounts for 4 to 10% of pregnancy-related deaths and leads to a high incidence of ectopic site gestations in future pregnancies. Medical management has emerged as a safe alternative to surgery and holds promise for preservation of future fertility; however, surgery remains an acceptable modality. We found that careful and strategic choice of management pathway can make all the difference to a favorable outcome. As emergency physicians, we need to be aware of the possibility of abdominal ectopic pregnancy in such presentations and its severe consequences if it remains undiagnosed. PMID- 26868919 TI - Loss of PPARalpha perpetuates sex differences in stroke reflected by peripheral immune mechanisms. AB - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor transcription factor that plays a role in immune regulation. Because of its expression in cerebral tissue and immune cells, PPARalpha has been examined as an important regulator in immune-based neurological diseases. Many studies have indicated that pre-treatment of animals with PPARalpha agonists induces protection against stroke. However, our previous reports indicate that protection is only in males, not females, and can be attributed to different PPARalpha expression between the sexes. In the current study, we examine how loss of PPARalpha affects male and female mice in experimental stroke. Male and female PPARalpha knockout mice were subject to middle cerebral artery occlusion (MCAO) or sham surgery, and the ischemic (local) or spleen specific (peripheral) immune response was examined 96 h after reperfusion. We found that loss of PPARalpha perpetuated sex differences in stroke, and this was driven by the peripheral, not local, immune response. Specifically we observed an increase in peripheral pro inflammatory and adhesion molecule gene expression in PPARalpha KO males after MCAO compared to females. Our data supports previous evidence that PPARalpha plays an important role in sex differences in the immune response to disease, including stroke. PMID- 26868920 TI - Understanding the Haldane effect. PMID- 26868921 TI - Thirty-year trends in heart failure hospitalization and mortality rates and the prognostic impact of co-morbidity: a Danish nationwide cohort study. AB - AIMS: We examined 30-year nationwide trends in heart failure hospitalization and mortality rates, and the prognostic impact of co-morbidity. METHODS AND RESULTS: We conducted a population-based cohort study of 317 161 patients with first-time inpatient hospitalizations for heart failure during 1983-2012. We computed the standardized hospitalization rate and 5-year mortality risk. Co-morbidity levels and calendar periods of diagnosis were compared by means of mortality rate ratios (MRRs) based on Cox regression. The standardized hospitalization rate (per 100 000 persons) decreased between 1983 and 2012 by 25% for women (from 192 to 144) and by 14% for men (from 217 to 186). The decrease reflected an average annual 1% increase until 2000 and a 3.5% decline thereafter. Between 1983-1987 and 2008 2012, 1-year mortality declined from 45% to 33% and 1- to 5-year mortality from 59% to 43%. The decline occurred independently of patients' co-morbidity levels. Comparing 2008-2012 with 1983-1987, the 5-year age-, sex-, and co-morbidity adjusted MRR was 0.57 [95% confidence interval (CI) 0.56-0.58]. Using low co morbidity as reference, the adjusted 5-year MRR in 2003-2007 was increased by 43% for moderate, 66% for severe, and 2.2-fold for very severe co-morbidity. The magnitude of co-morbidity-associated mortality increased over time and was highest in the youngest patients. CONCLUSIONS: Hospitalization rates for heart failure have declined markedly since 2000 in Denmark. One- and five-year mortality declined >40% over the last three decades. The decline in mortality occurred for patients with all levels of co-morbidity, but co-morbidity burden was a strong prognostic factor. PMID- 26868922 TI - Resting heart rate, physiological stress and disadvantage in Aboriginal and Torres Strait Islander Australians: analysis from a cross-sectional study. AB - BACKGROUND: Lower socioeconomic status has been linked to long-term stress, which can manifest in individuals as physiological stress. The aim was to explore the relationship between low socioeconomic status and physiological stress in Aboriginal and Torres Strait Islander Australians. METHODS: Using data from the eGFR Study (a cross-sectional study of 634 Indigenous Australians in urban and remote areas of northern and central Australia), we examined associations between resting heart rate and demographic, socioeconomic, and biomedical factors. An elevated resting heart rate has been proposed as a measure of sustained stress activation and was used as a marker of physiological stress. Relationships were assessed between heart rate and the above variables using univariate and multiple regression analyses. RESULTS: We reported a mean resting heart rate of 74 beats/min in the cohort (mean age 45 years). On multiple regression analysis, higher heart rate was found to be independently associated with Aboriginal ethnicity, being a current smoker, having only primary level schooling, higher HbA1c and higher diastolic blood pressure (model R(2) 0.25). CONCLUSIONS: Elevated resting heart rate was associated with lower socioeconomic status and poorer health profile in Aboriginal and Torres Strait Islander Australians. Higher resting heart rate may be an indicator of stress and disadvantage in this population at high risk of chronic diseases. PMID- 26868924 TI - The final moments of landing in bumblebees, Bombus terrestris. AB - In comparison to other insects, like honeybees, bumblebees are very effective pollinators. Even though landing is a crucial part of pollination, little is known about how bumblebees orchestrate the final, critical moments of landing. Here, we use high-speed recordings to capture the fine details of the landing behaviour of free-flying bumblebees (Bombus terrestris), while landing on a flat platform with different orientations. We find that the bees have a fairly constant body and head orientation at the moment of leg extension, irrespective of platform tilt. At the same moment in time, the distance to the platform is held constant at around 8 mm (with the exception of low platform tilts). The orientation of the antennae and the first appendage that touches the platform vary between platform orientations, while the duration of the hover phase does not. Overall, the final moments of landing in bumblebees and their close relatives, the honeybees, are similar. However, the distance to the platform at the moment of leg extension and the duration of the hover phase are different in bumblebees and honeybees, suggesting that they are primarily adapted to land on surfaces with different orientations. PMID- 26868923 TI - Visual response properties of neurons in four areas of the avian pallium. AB - In the present study we investigate the visual responsiveness of neurons in the entopallium, arcopallium, nidopallium, and hippocampus of pigeons. Pigeons were presented with 12 different stimuli, including three stimuli of a pigeon (a portrait of a pigeon's face, a profile view of a pigeon's face, and a picture of a whole pigeon). A total of 53 cells were recorded from the entopallium, 65 from the arcopallium, 32 from the nidopallium, and 67 from the hippocampus. Although a number of neurons were selective for certain colours and shapes, no neurons were solely selective for the three pigeon stimuli. This finding contrasts with previous studies across a range of mammals demonstrating selective firing to images of conspecifics. Rather than reflecting an absence of these cells in pigeons, we argue our findings may reflect the difficulty pigeons have in understanding the correspondence between 2D representations of 3D stimuli. PMID- 26868925 TI - A survey of mindset theories of intelligence and medical error self-reporting among pediatric housestaff and faculty. AB - BACKGROUND: Intelligence theory research has illustrated that people hold either "fixed" (intelligence is immutable) or "growth" (intelligence can be improved) mindsets and that these views may affect how people learn throughout their lifetime. Little is known about the mindsets of physicians, and how mindset may affect their lifetime learning and integration of feedback. Our objective was to determine if pediatric physicians are of the "fixed" or "growth" mindset and whether individual mindset affects perception of medical error reporting. METHODS: We sent an anonymous electronic survey to pediatric residents and attending pediatricians at a tertiary care pediatric hospital. Respondents completed the "Theories of Intelligence Inventory" which classifies individuals on a 6-point scale ranging from 1 (Fixed Mindset) to 6 (Growth Mindset). Subsequent questions collected data on respondents' recall of medical errors by self or others. RESULTS: We received 176/349 responses (50 %). Participants were equally distributed between mindsets with 84 (49 %) classified as "fixed" and 86 (51 %) as "growth". Residents, fellows and attendings did not differ in terms of mindset. Mindset did not correlate with the small number of reported medical errors. CONCLUSIONS: There is no dominant theory of intelligence (mindset) amongst pediatric physicians. The distribution is similar to that seen in the general population. Mindset did not correlate with error reports. PMID- 26868926 TI - Interferon-gamma enhances the efficacy of autogenous bone grafts by inhibiting postoperative bone resorption in rat calvarial defects. AB - PURPOSE: Interferon (IFN)-gamma is a major cytokine produced by immune cells that plays diverse roles in modulating both the immune system and bone metabolism, but its role in autogenous bone grafting remains unknown. Here, we present that local IFN-gamma administration improved the efficacy of autogenous bone graft treatment in an experimental rat model. METHODS: An autogenous bone graft model was prepared with critically sized rat calvariae defects. Four weeks (w) after bone graft implantation, rats were treated locally with IFN-gamma or were not treated. The effect of IFN-gamma on bone formation was evaluated for up to 8w with micro computed tomography, quantitative histomorphometry, and Von Kossa staining. Osteoclastogenesis was assessed by tartrate-resistant acid phosphatase staining. Immunohistochemistry staining or quantitative polymerase chain reactions were used to estimate the expression of osteoclast differentiation factor and inflammatory cytokines including tumor necrosis factor (TNF)-alpha, a well-known stimulant of osteoclastogenesis and an inhibitor of osteoblast activity, in defects. RESULTS: Newly formed bone gradually replaced the autogenous bone grafts within 4w, although severe bone resorption with osteoclastogenesis and TNF-alpha expression occurred after 6w in the absence of IFN-gamma administration. IFN gamma administration markedly attenuated bone loss, osteoclastogenesis, and TNF alpha expression, while it enhanced bone formation at 8w. CONCLUSION: Local IFN gamma administration promoted bone formation in autogenous bone grafts possibly via regulating osteoclastogenesis and TNF-alpha expression. The data provide insights into the potential roles of IFN-gamma in autogenous bone grafting. PMID- 26868927 TI - A digital approach for one-step formation of the supra-implant emergence profile with an individualized CAD/CAM healing abutment. AB - PURPOSE: This Technical Procedure describes a novel workflow for a one-step formation of the supra-implant emergence profile in the esthetic zone - the 'Digitally Flip Technique' (DFT). METHODS: After implant placement, a post operative intra-oral optical scan (IOS) was performed to capture the final three dimensional implant position. Based on the superimposition of the digitally slice wise DICOM-segmentation of the digitally flipped (mirrored) contra-lateral tooth and the STL-file of the IOS, an individualized healing abutment was CAD/CAM fabricated out of PMMA-based restoration material in a fully digital workflow and seated at the stage of reopening surgery. One single treatment step was necessary for final modulation of the supra-implant mucosa architecture in order to mimic the morphological emergence profile of the contra-lateral tooth within a short span time frame of four days after insertion of the individualized healing abutment. CONCLUSIONS: The implant crown emergence profile could be shaped immediately after reopening according to the three-dimensional radiographic contour of the digitally flipped contra-lateral tooth. Estimating the emergence profile or time-consuming step-by-step conditioning of the mucosa through an additionally produced implant provisional was therefore avoided. PMID- 26868928 TI - Survey of uniparental genetic markers in the Maltese cattle breed reveals a significant founder effect but does not indicate local domestication. PMID- 26868930 TI - Receipt of evidence-based brief cessation interventions by health professionals and use of cessation assisted treatments among current adult cigarette-only smokers: National Adult Tobacco Survey, 2009-2010. AB - BACKGROUND: Helping tobacco smokers to quit during a medical visit is a clinical and public health priority. Research suggests that most health professionals engage their patients in at least some of the '5 A's' of the brief cessation intervention recommended in the U.S. Public Health Service Clinical Practice Guideline, but information on the extent to which patients act on this intervention is uncertain. We assessed current cigarette-only smokers' self reported receipt of the 5 A's to determine the odds of using optimal cessation assisted treatments (a combination of counseling and medication). METHODS: Data came from the 2009-2010 National Adult Tobacco Survey (NATS), a nationally representative landline and mobile phone survey of adults aged >=18 years. Among current cigarette-only smokers who visited a health professional in the past 12 months, we assessed patients' self-reported receipt of the 5 A's, use of the combination of counseling and medication for smoking cessation, and use of other cessation treatments. We used logistic regression to examine whether receipt of the 5 A's during a recent clinic visit was associated with use of cessation treatments (counseling, medication, or a combination of counseling and medication) among current cigarette-only smokers. RESULTS: In this large sample (N = 10,801) of current cigarette-only smokers who visited a health professional in the past 12 months, 6.3 % reported use of both counseling and medication for smoking cessation within the past year. Other assisted cessation treatments used to quit were: medication (19.6 %); class or program (3.8 %); one-on-one counseling (3.7 %); and telephone quitline (2.6 %). Current cigarette-only smokers who reported receiving all 5 A's during a recent clinic visit were more likely to use counseling (odds ratio [OR]: 11.2, 95 % confidence interval [CI]: 7.1-17.5), medication (OR: 6.2, 95 % CI: 4.3-9.0), or a combination of counseling and medication (OR: 14.6, 95 % CI: 9.3-23.0), compared to smokers who received one or none of the 5 A's components. CONCLUSIONS: Receipt of the '5 A's' intervention was associated with a significant increase in patients' use of recommended counseling and medication for cessation. It is important for health professionals to deliver all 5 A's when conducting brief cessation interventions with patients who smoke. PMID- 26868931 TI - Two new lipid-regulating drugs. AB - ?Evolocumab (Repatha-Amgen Ltd) and ?alirocumab (Praluent-Sanofi) are the first in a novel class of lipid-regulating drugs, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, to be licensed in the UK. Both drugs have marketing authorisation for the treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia and are administered by subcutaneous injection. Here we consider the evidence for evolocumab and alirocumab in the management of primary hypercholesterolaemia and dyslipidaemias. PMID- 26868929 TI - Structure of ring-shaped Abeta42 oligomers determined by conformational selection. AB - The oligomerization of amyloid beta (Abeta) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer's disease. However, it has been challenging to characterize the tertiary and quaternary structures of Abeta peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Abeta42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Abeta peptide self-assembly. PMID- 26868932 TI - Total ankle joint replacement. AB - Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications. PMID- 26868933 TI - Quantitative profiling of sphingolipids in wild Cordyceps and its mycelia by using UHPLC-MS. AB - In the present study, 101 sphingolipids in wild Cordyceps and its five mycelia were quantitatively profiled by using a fully validated UHPLC-MS method. The results revealed that a general rank order for the abundance of different classes of sphingolipids in wild Cordyceps and its mycelia is sphingoid bases/ceramides > phosphosphingolipids > glycosphingolipids. However, remarkable sphingolipid differences between wild Cordyceps and its mycelia were observed. One is that sphingoid base is the dominant sphingolipid in wild Cordyceps, whereas ceramide is the major sphingolipid in mycelia. Another difference is that the abundance of sphingomyelins in wild Cordyceps is almost 10-folds higher than those in most mycelia. The third one is that mycelia contain more inositol phosphorylceramides and glycosphingolipids than wild Cordyceps. Multivariate analysis was further employed to visualize the difference among wild Cordyceps and different mycelia, leading to the identification of respective sphingolipids as potential chemical markers for the differentiation of wild Cordyceps and its related mycelia. This study represents the first report on the quantitative profiling of sphingolipids in wild Cordyceps and its related mycelia, which provided comprehensive chemical evidence for the quality control and rational utilization of wild Cordyceps and its mycelia. PMID- 26868934 TI - [Methods can influence the value of copeptin to rule-out acute myocardial infarction without ST segment elevation]. PMID- 26868935 TI - An electrochemical biosensor to simultaneously detect VEGF and PSA for early prostate cancer diagnosis based on graphene oxide/ssDNA/PLLA nanoparticles. AB - Early diagnosis of prostate cancer (PCa) is critical for the prevention of metastasis and for early treatment; therefore, a simple and accurate device must be developed for this purpose. In this study, we reported a novel fabrication method for producing a dual-modality biosensor that can simultaneously detect vascular endothelial growth factor (VEGF) and prostate-specific antigen (PSA) in human serum for early diagnosis of PCa. This biosensor was constructed by coating graphene oxide/ssDNA (GO-ssDNA) on an Au-electrode for VEGF detection, and incorporated with poly-L-lactide nanoparticles (PLLA NPs) for signal amplification and PSA detection. The results showed that this biosensor has wide liner detection ranges (0.05-100ng/mL for VEGF and 1-100ng/mL for PSA), as well as high levels of sensitivity and selectivity (i.e., resisting interference from external factors, such as glucose, ascorbic acid human serum protein, immunoglobulin G, and immunoglobulin M), and demonstrated a high correlation with an enzyme-linked immunosorbent assay for sample detection in patients. Therefore, this biosensor could be utilized for early clinical diagnosis of PCa in the future. PMID- 26868937 TI - Photoaggravated pompholyx. PMID- 26868936 TI - Effect of crop plants on fitness costs associated with resistance to Bacillus thuringiensis toxins Cry1Ac and Cry2Ab in cabbage loopers. AB - Fitness costs associated with resistance to Bacillus thuringiensis (Bt) toxins critically impact the development of resistance in insect populations. In this study, the fitness costs in Trichoplusia ni strains associated with two genetically independent resistance mechanisms to Bt toxins Cry1Ac and Cry2Ab, individually and in combination, on four crop plants (cabbage, cotton, tobacco and tomato) were analyzed, in comparison with their near-isogenic susceptible strain. The net reproductive rate (R0) and intrinsic rate of increase (r) of the T. ni strains, regardless of their resistance traits, were strongly affected by the host plants. The ABCC2 gene-linked mechanism of Cry1Ac resistance was associated with relatively low fitness costs, while the Cry2Ab resistance mechanism was associated with higher fitness costs. The fitness costs in the presence of both resistance mechanisms in T. ni appeared to be non-additive. The relative fitness of Bt-resistant T. ni depended on the specific resistance mechanisms as well as host plants. In addition to difference in survivorship and fecundity, an asynchrony of adult emergence was observed among T. ni with different resistance mechanisms and on different host plants. Therefore, mechanisms of resistance and host plants available in the field are both important factors affecting development of Bt resistance in insects. PMID- 26868940 TI - Relationship between diagonal earlobe creases and coronary artery disease as determined via angiography. AB - OBJECTIVE: This study was designed to examine the prevalence of unilateral and bilateral diagonal earlobe creases (DELCs) with respect to the diagnosis of coronary heart disease (CHD). METHODS: A total of 558 consecutive participants (402 males and 156 females) aged 36-91 years who underwent coronary angiography were enrolled in this study. The participants were classified as being without a DELC, having a unilateral DELC and having bilateral DELCs; participants with either a unilateral DELC or bilateral DELCs were defined as participants with DELCs. Significant CHD was defined as at least one major vessel with >50% stenosis, and coronary atherosclerosis severity was defined using the Gensini scoring system. RESULTS: In the present study, bilateral DELCs were more frequently among male (p=0.001), CHD (p=0.000), older people (p=0.000) and those with more severe coronary artery atherosclerosis (p=0.000). The results of the multiple regression analyses indicated that DELCs (OR, 4.861; 95% CI 3.093 to 7.642, p=0.000) remained independently associated with a risk of CHD. It was assumed that participants without a DELC have a certain background risk for CHD (OR is assumed to be 1); the results of the multivariate logistic regression indicated that the relative risk of CHD among participants with bilateral DELCs was 5.690 among all participants (OR, 5.690; 95% CI 3.450 to 9.384, p=0.000), 5.436 among male participants (OR, 5.436; 95% CI 2.808 to 10.523, p=0.000) and 7.148 among female participants (OR, 7.148; 95% CI 3.184 to 16.049, p=0.000). Moreover, a positive association between DELC and age (SI=1.21, SIM=1.65, AP =0.132), gender (SI=2.09, SIM=0.81, AP=0.49) and smoking status (SI=1.49, SIM=0.73, AP=0.29) was found, respectively. CONCLUSIONS: The results of the present study indicated that DELCs are a simple and a feasible means of identifying CHD. However, the exact mechanism underlying the relationship between DELCs and CHD warrants further study. PMID- 26868941 TI - New South Wales Child Development Study (NSW-CDS): an Australian multiagency, multigenerational, longitudinal record linkage study. AB - PURPOSE: The initial aim of this multiagency, multigenerational record linkage study is to identify childhood profiles of developmental vulnerability and resilience, and to identify the determinants of these profiles. The eventual aim is to identify risk and protective factors for later childhood-onset and adolescent-onset mental health problems, and other adverse social outcomes, using subsequent waves of record linkage. The research will assist in informing the development of public policy and intervention guidelines to help prevent or mitigate adverse long-term health and social outcomes. PARTICIPANTS: The study comprises a population cohort of 87,026 children in the Australian State of New South Wales (NSW). The cohort was defined by entry into the first year of full time schooling in NSW in 2009, at which time class teachers completed the Australian Early Development Census (AEDC) on each child (with 99.7% coverage in NSW). The AEDC data have been linked to the children's birth, health, school and child protection records for the period from birth to school entry, and to the health and criminal records of their parents, as well as mortality databases. FINDINGS TO DATE: Descriptive data summarising sex, geographic and socioeconomic distributions, and linkage rates for the various administrative databases are presented. Child data are summarised, and the mental health and criminal records data of the children's parents are provided. FUTURE PLANS: In 2015, at age 11 years, a self-report mental health survey was administered to the cohort in collaboration with government, independent and Catholic primary school sectors. A second record linkage, spanning birth to age 11 years, will be undertaken to link this survey data with the aforementioned administrative databases. This will enable a further identification of putative risk and protective factors for adverse mental health and other outcomes in adolescence, which can then be tested in subsequent record linkages. PMID- 26868943 TI - Decision analytic model exploring the cost and cost-offset implications of street triage. AB - OBJECTIVES: To determine if street triage is effective at reducing the total number of people with mental health needs detained under section 136, and is associated with cost savings compared to usual police response. DESIGN: Routine data from a 6-month period in the year before and after the implementation of a street triage scheme were used to explore detentions under section 136, and to populate a decision analytic model to explore the impact of street triage on the cost to the NHS and the criminal justice sector of supporting people with a mental health need. SETTING: A predefined area of Sussex, South East England, UK. PARTICIPANTS: All people who were detained under section 136 within the predefined area or had contact with the street triage team. INTERVENTIONS: The street triage model used here was based on a psychiatric nurse attending incidents with a police constable. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was change in the total number of detentions under section 136 between the before and after periods assessed. Secondary analysis focused on whether the additional costs of street triage were offset by cost savings as a result of changes in detentions under section 136. RESULTS: Detentions under section 136 in the street triage period were significantly lower than in the usual response period (118 vs 194 incidents, respectively; chi(2) (1df) 18.542, p<0.001). Total NHS and criminal justice costs were estimated to be L1043 in the street triage period compared to L1077 in the usual response period. CONCLUSIONS: Investment in street triage was offset by savings as a result of reduced detentions under section 136, particularly detentions in custody. Data available did not include assessment of patient outcomes, so a full economic evaluation was not possible. PMID- 26868942 TI - Development of a clinical prediction rule to improve peripheral intravenous cannulae first attempt success in the emergency department and reduce post insertion failure rates: the Vascular Access Decisions in the Emergency Room (VADER) study protocol. AB - INTRODUCTION: Peripheral intravenous cannula (PIVC) insertion is one of the most common clinical interventions performed in emergency care worldwide. However, factors associated with successful PIVC placement and maintenance are not well understood. This study seeks to determine the predictors of first time PIVC insertion success in emergency department (ED) and identify the rationale for removal of the ED inserted PIVC in patients admitted to the hospital ward. Reducing failed insertion attempts and improving peripheral intravenous cannulation practice could lead to better staff and patient experiences, as well as improving hospital efficiency. METHODS AND ANALYSIS: We propose an observational cohort study of PIVC insertions in a patient population presenting to ED, with follow-up observation of the PIVC in subsequent admissions to the hospital ward. We will collect specific PIVC observational data such as; clinician factors, patient factors, device information and clinical practice variables. Trained researchers will gather ED PIVC insertion data to identify predictors of insertion success. In those admitted from the ED, we will determine the dwell time of the ED-inserted PIVC. Multivariate regression analyses will be used to identify factors associated with insertions success and PIVC failure and standard statistical validation techniques will be used to create and assess the effectiveness of a clinical predication rule. ETHICS AND DISSEMINATION: The findings of our study will provide new evidence to improve insertion success rates in the ED setting and identify strategies to reduce premature device failure for patients admitted to hospital wards. Results will unravel a complexity of factors that contribute to unsuccessful PIVC attempts such as patient and clinician factors along with the products, technologies and infusates used. TRIAL REGISTRATION NUMBER: ACTRN12615000588594; Pre-results. PMID- 26868944 TI - Continuing reductions in HPV 16/18 in a population with high coverage of bivalent HPV vaccination in England: an ongoing cross-sectional study. AB - OBJECTIVES: The human papillomavirus (HPV) immunisation programme in England was introduced in 2008. Monitoring changes in type-specific HPV prevalence allows assessment of the population impact of this vaccination programme. METHODS: Residual vulva-vaginal swab specimens were collected from young sexually active women (aged 16-24 years) attending for chlamydia screening across England. Specimens were collected between 2010 and 2013 for type-specific HPV-DNA testing. HPV prevalence was compared to a similar survey conducted in 2008 prior to the introduction of HPV vaccination. RESULTS: A total of 7321 specimens collected in the postvaccination period, and 2354 specimens from the prevaccination period were included in this analysis. Among the individuals aged 16-18 years, with an estimated vaccination coverage of 67%, the prevalence of HPV16/18 infection decreased from 17.6% in 2008 to 6.1% in the postvaccination period. Within the postvaccination period, there was a trend towards lower HPV16/18 prevalence with higher vaccination coverage and increasing time since vaccine introduction from 8.5% in the period 2-3 years postvaccination to 4.0% in the period 4-5 years postvaccination. The prevalence of HPV31 reduced from 3.7% in the prevaccination period to 0.9% after vaccine introduction, although this no longer reached statistical significance after additional consideration of the uncertainty due to the assay change. Smaller reductions were seen in the individuals aged 19-21 years with lower estimated vaccination coverage, but there was no evidence of a reduction in the older unvaccinated women. Some overall increase in non-vaccine types was seen in the youngest age groups (ORs (95% CI); 1.3 (1.0 to 1.7) and 1.5 (1.1 to 2.0) for individuals aged 16-18 and 19-21 years, respectively, when adjusted for known population changes and the change in assay) although this should be interpreted with caution given the potential unmasking effect. CONCLUSIONS: These data demonstrate a reduction in the HPV vaccine types in the age group with the highest HPV vaccination coverage. PMID- 26868945 TI - Population characteristics, mechanisms of primary care and premature mortality in England: a cross-sectional study. AB - OBJECTIVES: Health systems with strong primary care tend to have better population outcomes, but in many countries demand for care is growing. We sought to identify mechanisms of primary care that influence premature mortality. DESIGN: We developed a conceptual model of the mechanisms by which primary care influences premature mortality, and undertook a cross-sectional study in which population and primary care variables reflecting the model were used to explain variations in mortality of those aged under 75 years. The premature standardised mortality ratios (SMRs) for each practice, available from the Department of Health, had been calculated from numbers of deaths in the 5 years from 2006 to 2010. A regression model was undertaken with explanatory variables for the year 2009/2010, and repeated to check stability using data for 2008/2009 and 2010/2011. SETTING: All general practices in England were eligible for inclusion and, of the total of 8290, complete data were available for 7858. RESULTS: Population variables, particularly deprivation, were the most powerful predictors of premature mortality, but the mechanisms of primary care depicted in our model also affected mortality. The number of GPs/1000 population and detection of hypertension were negatively associated with mortality. In less deprived practices, continuity of care was also negatively associated with mortality. CONCLUSIONS: Greater supply of primary care is associated with lower premature mortality even in a health system that has strong primary care (England). Health systems need to sustain the capacity of primary care to deliver effective care, and should assist primary care providers in identifying and meeting the needs of socioeconomically deprived groups. PMID- 26868946 TI - What is a medical decision? A taxonomy based on physician statements in hospital encounters: a qualitative study. AB - OBJECTIVE: The medical literature lacks a comprehensive taxonomy of decisions made by physicians in medical encounters. Such a taxonomy might be useful in understanding the physician-centred, patient-centred and shared decision-making in clinical settings. We aimed to identify and classify all decisions emerging in conversations between patients and physicians. DESIGN: Qualitative study of video recorded patient-physician encounters. PARTICIPANTS AND SETTING: 380 patients in consultations with 59 physicians from 17 clinical specialties and three different settings (emergency room, ward round, outpatient clinic) in a Norwegian teaching hospital. A randomised sample of 30 encounters from internal medicine was used to identify and classify decisions, a maximum variation sample of 20 encounters was used for reliability assessments, and the remaining encounters were analysed to test for applicability across specialties. RESULTS: On the basis of physician statements in our material, we developed a taxonomy of clinical decisions--the Decision Identification and Classification Taxonomy for Use in Medicine (DICTUM). We categorised decisions into 10 mutually exclusive categories: gathering additional information, evaluating test results, defining problem, drug-related, therapeutic procedure-related, legal and insurance-related, contact-related, advice and precaution, treatment goal, and deferment. Four-coder inter-rater reliability using Krippendorff's alpha was 0.79. CONCLUSIONS: DICTUM represents a precise, detailed and comprehensive taxonomy of medical decisions communicated within patient-physician encounters. Compared to previous normative frameworks, the taxonomy is descriptive, substantially broader and offers new categories to the variety of clinical decisions. The taxonomy could prove helpful in studies on the quality of medical work, use of time and resources, and understanding of why, when and how patients are or are not involved in decisions. PMID- 26868947 TI - Impact of high ambient temperature on unintentional injuries in high-income countries: a narrative systematic literature review. AB - OBJECTIVES: Given the likelihood of increased hot weather due to climate change, it is crucial to have prevention measures in place to reduce the health burden of high temperatures and heat waves. The aim of this review is to summarise and evaluate the evidence on the effects of summertime weather on unintentional injuries in high-income countries. DESIGN: 3 databases (Global Public Health, EMBASE and MEDLINE) were searched by using related keywords and their truncations in the title and abstract, and reference lists of key studies were scanned. Studies reporting heatstroke and intentional injuries were excluded. RESULTS: 13 studies met our inclusion criteria. 11 out of 13 studies showed that the risk of unintentional injuries increases with increasing ambient temperatures. On days with moderate temperatures, the increased risk varied between 0.4% and 5.3% for each 1 degrees C increase in ambient temperature. On extreme temperature days, the risk of injuries decreased. 2 out of 3 studies on occupational accidents found an increase in work-related accidents during high temperatures. For trauma hospital admissions, 6 studies reported an increase during hot weather, whereas 1 study found no association. The evidence for impacts on injuries by subgroups such as children, the elderly and drug users was limited and inconsistent. CONCLUSIONS: The present review describes a broader range of types of unintentional fatal and non-fatal injuries (occupational, trauma hospital admissions, traffic, fire entrapments, poisoning and drug overdose) than has previously been reported. Our review confirms that hot weather can increase the risk of unintentional injuries and accidents in high-income countries. The results are useful for injury prevention strategies. PMID- 26868948 TI - Drinking patterns of adolescents who develop alcohol use disorders: results from the Victorian Adolescent Health Cohort Study. AB - OBJECTIVE: We identify drinking styles that place teens at greatest risk of later alcohol use disorders (AUD). DESIGN: Population-based cohort study. SETTING: Victoria, Australia. PARTICIPANTS: A representative sample of 1943 adolescents living in Victoria in 1992. OUTCOME MEASURES: Teen drinking was assessed at 6 monthly intervals (5 waves) between mean ages 14.9 and 17.4 years and summarised across waves as none, one, or two or more waves of: (1) frequent drinking (3+ days in the past week), (2) loss of control over drinking (difficulty stopping, amnesia), (3) binge drinking (5+ standard drinks in a day) and (4) heavy binge drinking (20+ and 11+ standard drinks in a day for males and females, respectively). Young Adult Alcohol Use Disorder (AUD) was assessed at 3 yearly intervals (3 waves) across the 20s (mean ages 20.7 through 29.1 years). RESULTS: We show that patterns of teen drinking characterised by loss of control increase risk for AUD across young adulthood: loss of control over drinking (one wave OR 1.4, 95% CI 1.1 to 1.8; two or more waves OR 1.9, CI 1.4 to 2.7); binge drinking (one wave OR 1.7, CI 1.3 to 2.3; two or more waves OR 2.0, CI 1.5 to 2.6), and heavy binge drinking (one wave OR 2.0, CI 1.4 to 2.8; two or more waves OR 2.3, CI 1.6 to 3.4). This is not so for frequent drinking, which was unrelated to later AUD. Although drinking was more common in males, there was no evidence of sex differences in risk relationships. CONCLUSIONS: Our results extend previous work by showing that patterns of drinking that represent loss of control over alcohol consumption (however expressed) are important targets for intervention. In addition to current policies that may reduce overall consumption, emphasising prevention of more extreme teenage bouts of alcohol consumption appears warranted. PMID- 26868949 TI - Evaluating the clinical and cost effectiveness of a behaviour change intervention for lowering cardiovascular disease risk for people with severe mental illnesses in primary care (PRIMROSE study): study protocol for a cluster randomised controlled trial. AB - BACKGROUND: People with severe mental illnesses die up to 20 years earlier than the general population, with cardiovascular disease being the leading cause of death. National guidelines recommend that the physical care of people with severe mental illnesses should be the responsibility of primary care; however, little is known about effective interventions to lower cardiovascular disease risk in this population and setting. Following extensive peer review, funding was secured from the United Kingdom National Institute for Health Research (NIHR) to deliver the proposed study. The aim of the trial is to test the effectiveness of a behavioural intervention to lower cardiovascular disease risk in people with severe mental illnesses in United Kingdom General Practices. METHODS/DESIGN: The study is a cluster randomised controlled trial in 70 GP practices for people with severe mental illnesses, aged 30 to 75 years old, with elevated cardiovascular disease risk factors. The trial will compare the effectiveness of a behavioural intervention designed to lower cardiovascular disease risk and delivered by a practice nurse or healthcare assistant, with standard care offered in General Practice. A total of 350 people will be recruited and followed up at 6 and 12 months. The primary outcome is total cholesterol level at the 12-month follow-up and secondary outcomes include blood pressure, body mass index, waist circumference, smoking status, quality of life, adherence to treatments and services and behavioural measures for diet, physical activity and alcohol use. An economic evaluation will be carried out to determine the cost effectiveness of the intervention compared with standard care. DISCUSSION: The results of this pragmatic trial will provide evidence on the clinical and cost effectiveness of the intervention on lowering total cholesterol and addressing multiple cardiovascular disease risk factors in people with severe mental illnesses in GP Practices. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13762819. Date of Registration: 25 February 2013. Date and Version Number: 27 August 2014 Version 5. PMID- 26868950 TI - Perceived diagnostic delay and cancer-related distress: a cross-sectional study of patients with colorectal cancer. AB - OBJECTIVE: This study aimed to examine the effect of perceived diagnostic delay on cancer-related distress and determine whether fear of cancer-recurrence and quality of life mediate this relationship. METHODS: Cross-sectional study in which 311 colorectal cancer (CRC) survivors in Scotland completed a survey, which included questions on cancer-related distress (IES-R), perceived diagnostic delay, quality of life (trial outcome index of the FACT-C: FACT-C TOI) and fear of cancer recurrence. Fifteen patients withheld consent to data matching with medical records, leaving a sample size of 296. Participants were an average of 69 years old (range 56 to 81) and between 3.5 and 12 years post-diagnosis. Multiple regressions were used to test predictors of distress and regression and bootstrapping to test for mediation. RESULTS: Perceived diagnostic delay was correlated with higher cancer-related distress, while objective markers of diagnostic delay (disease stage at diagnosis and treatment received) were not. Some of the relationship between perceived diagnostic delay and cancer-related distress was mediated by quality of life, but not by fear of cancer recurrence. CONCLUSIONS: Perceived diagnostic delay was associated with higher cancer-related distress among CRC survivors. While poorer quality of life partly explained such associations, fear of cancer recurrence, stage at diagnosis and treatment did not. The exact features of diagnostic delay that are associated with cancer related distress remain unclear. Future research should examine the experiences patients go through prior to diagnosis that may increase distress, in an effort to improve our understanding of the factors affecting emotional wellbeing among CRC survivors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26868951 TI - Suicidal ideation in patients undergoing brain tumor surgery: prevalence and risk factors. AB - PURPOSE: Suicidal ideation (SI) is an important complication in cancer patients that should be promptly recognized and adequately managed. We investigated the prevalence rate and correlates of pre-operative SI in brain tumor (BT) patients admitted for elective BT surgery. METHODS: Two hundred and eleven consecutive patients (70 % women; mean age 55.9 +/- 15.4 years) scheduled for BT surgery were evaluated for SI ("suicidal thought" item from the Beck Depression Inventory-II), depressive/anxiety symptom severity (Hospital Anxiety and Depression scale (HADS)), health-related quality of life (SF-36 scale), functional status (Barthel Index), and psychiatric histories and treatments. The majority of patients were diagnosed with meningioma (39 %) and high-grade glioma (17 %). RESULTS: SI was self-reported by 12 (6 %) patients. Patients expressing SI were most commonly diagnosed with meningioma (50 %). Patients with SI were more likely to have a past history of psychiatric disorders, scored higher on the HADS anxiety subscale, and reported worse health-related quality of life across physical and mental health domains. In multivariate regression analyses, worse perceived mental health was associated with increased risk for SI independently from clinical, sociodemographic, and other patient-oriented variables considered in the study. CONCLUSIONS: SI was self-reported by 6 % of BT patients before surgical intervention and was associated with a past history of psychiatric disorders and worse perceived health status. Poor mental health was an independent correlate of SI. The perception of health status by a patient should be considered as an important determinant of poor mental health in BT patients. PMID- 26868953 TI - Which pain intensity scale from the Brief Pain Inventory correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia? AB - PURPOSE: The purpose of this study was to assess which pain intensity dimension scale (worst, least, average, or current pain) from the Brief Pain Inventory (BPI) correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia. METHODS: Breast cancer patients scheduled to receive docetaxel, paclitaxel, or albumin-bound paclitaxel (nab-paclitaxel) were enrolled in the study. Patients completed an initial baseline questionnaire and subsequently filled out a diary based on the BPI on days 1-7, 14, and 21 for three consecutive treatment cycles. Pain scores for worst, least, average, and current pain intensity dimensions as well as pain interference scores were recorded in the diaries and questionnaires using the BPI. Worst, least, average, and current pain scores were correlated with functional pain interference scores using Spearman's rank correlation coefficients. A general linear mixed model of each functional interference measure was performed over time for cycles 1-3 with each pain intensity dimension scale. RESULTS: Among worst, average, least, and current joint pain dimensions, average joint pain scores correlated best with all BPI interference responses while average muscle pain scores correlated best with all BPI interference responses except for sleeping probability and normal work. CONCLUSION: We recommend the BPI scale measuring average pain for future studies evaluating pain scores in patients experiencing taxane-induced arthralgia and myalgia. PMID- 26868952 TI - Spontaneous intracranial haemorrhage in critically ill patients with malignancies. AB - PURPOSE: Limited data are available on the intracranial haemorrhage (ICH) developed in critically ill cancer patients during their stay in the intensive care unit (ICU). METHODS: All consecutive patients who underwent brain CT for suspicion of spontaneous intracerebral haemorrhage (ICH) with acute neurologic symptoms or signs developed during their ICU stay were retrospectively evaluated to identify predictors of ICH. RESULTS: Over the study period, a total of 273 patients underwent brain CT scanning for suspicion of ICH, with altered mentality in 202 (74 %), seizure in 43 (16 %), and hemiparesis in 34 (13 %). However, only 49 (18 %) patients had a final diagnosis of ICH. The most common type of haemorrhage was intracerebral in 34 patients (69 %), followed by subarachnoidal haemorrhage in 17 (35 %). In multiple logistic regression analysis, anisocoric pupils or abnormal pupil reflex (adjusted OR 7.939; 95 % CI, 2.315-27.228) was an independent predictor of ICH. In addition, higher positive end-expiratory pressure (adjusted OR 1.204; 95 % CI, 1.065-1.361) was significantly associated with ICH. However, platelet count was inversely associated with ICH (adjusted OR 0.993; 95 % CI 0.988-0.999). CONCLUSION: Brain CT scanning should be performed even in critically ill cancer patients, especially with risk factors and acute neurologic changes. PMID- 26868954 TI - Optical brush: Imaging through permuted probes. AB - The combination of computational techniques and ultrafast imaging have enabled sensing through unconventional settings such as around corners, and through diffusive media. We exploit time of flight (ToF) measurements to enable a flexible interface for imaging through permuted set of fibers. The fibers are randomly distributed in the scene and are packed on the camera end, thus making a brush-like structure. The scene is illuminated by two off-axis optical pulses. Temporal signatures of fiber tips in the scene are used to localize each fiber. Finally, by combining the position and measured intensity of each fiber, the original input is reconstructed. Unlike conventional fiber bundles with packed set of fibers that are limited by a narrow field of view (FOV), lack of flexibility, and extended coaxial precalibration, the proposed optical brush is flexible and uses off-axis calibration method based on ToF. The enabled brush form can couple to other types of ToF imaging systems. This can impact probe based applications such as, endoscopy, tomography, and industrial imaging and sensing. PMID- 26868955 TI - Dynamic Range Across Music Genres and the Perception of Dynamic Compression in Hearing-Impaired Listeners. AB - Dynamic range compression serves different purposes in the music and hearing-aid industries. In the music industry, it is used to make music louder and more attractive to normal-hearing listeners. In the hearing-aid industry, it is used to map the variable dynamic range of acoustic signals to the reduced dynamic range of hearing-impaired listeners. Hence, hearing-aided listeners will typically receive a dual dose of compression when listening to recorded music. The present study involved an acoustic analysis of dynamic range across a cross section of recorded music as well as a perceptual study comparing the efficacy of different compression schemes. The acoustic analysis revealed that the dynamic range of samples from popular genres, such as rock or rap, was generally smaller than the dynamic range of samples from classical genres, such as opera and orchestra. By comparison, the dynamic range of speech, based on recordings of monologues in quiet, was larger than the dynamic range of all music genres tested. The perceptual study compared the effect of the prescription rule NAL-NL2 with a semicompressive and a linear scheme. Music subjected to linear processing had the highest ratings for dynamics and quality, followed by the semicompressive and the NAL-NL2 setting. These findings advise against NAL-NL2 as a prescription rule for recorded music and recommend linear settings. PMID- 26868956 TI - Health-Related Quality of Life for Patients Who have In-Transit Melanoma Metastases Treated with Isolated Limb Perfusion. AB - BACKGROUND: The incidence of malignant melanoma is increasing, and up to 5 % of patients will experience in-transit metastases. Normally, the initial treatment is surgical excision, but when not possible, locoregional treatment options such as isolated limb perfusion (ILP) are an alternative. This study aimed to assess health-related quality of life (HRQoL) prospectively for patients whose in transit metastases is treated with ILP. More specifically, the study aimed to describe HRQoL for patients with in-transit extremity melanoma metastases, to describe changes in HRQoL after ILP, and to correlate HRQoL with local toxicity and clinical response after ILP. METHODS: The Functional Assessment of Cancer Therapy-Melanoma (FACT-M) consists of 51 items comprising the Functional Assessment of Cancer Therapy-General (FACT-G), the melanoma subscale , and the melanoma surgery scale. Forty-five patients answered the FACT-M questionnaire before ILP (52 procedures) and at 3, 6 and 12 months after ILP. Response and toxicity were analyzed and correlated with the changes in the HRQoL of the patients. RESULTS: Patients with in-transit metastasis have an HRQoL mainly influenced by tumor burden, defined as more or <10 tumors (FACT-M: 142.5 vs. 128.4 points; p = 0.02). After ILP, there was a trend toward a decrease in FACT-G (+0.1 vs. -7.3 points; p = 0.05) and FACT-M (+1.6 vs. -8.9 points; p = 0.08) when Wieberdink classifications 1-2 and 3-4 were compared at 3 months. A significant difference in FACT-G (+1.0 vs. -13.0 points; p = 0.04) was observed 12 months after ILP as well as a trend for FACT-M (+1.7 vs. -14.6 points; p = 0.08) when the patients who had a complete response were compared with those who did not. CONCLUSION: This study found that patients with in-transit metastases have an HRQoL mainly influenced by tumor burden. After ILP, there is an initial decrease in HRQoL due to local toxicity. After 12 months, the patients with a complete response maintained an HRQoL at baseline level, strengthening the use of ILP as a palliative treatment. PMID- 26868957 TI - Frequency of Resection After Preoperative Chemotherapy or Chemoradiotherapy for Gastric Adenocarcinoma. AB - OBJECTIVE: The purpose of this study was to determine differences in stage and resection rates for patients with gastric adenocarcinoma managed with upfront surgery, preoperative chemotherapy, or preoperative chemoradiation therapy . METHODS: The medical records of 8382 patients with gastric or gastroesophageal cancer treated from January 1995 to November 2014 were reviewed. Chi square and logistic regression analysis was used to identify differences in treatment groups and variables associated with resection. RESULTS: Of 533 patients evaluated for gastrectomy, 174 patients underwent upfront surgery, 90 underwent preoperative chemotherapy, and 269 underwent preoperative chemoradiation therapy. Patients treated with preoperative therapy had more advanced endoscopic ultrasound and computed tomography imaging findings. Preoperative treatment was completed in 81 % of patients administered chemotherapy and 93 % of patients administered chemoradiation. Progressive, unresectable, or metastatic disease was identified in 27 % of preoperative chemotherapy and 26 % of chemoradiation patients. Toxicity or worsening comorbidities associated with an inability to undergo resection were identified in 2 % of chemotherapy patients and 6 % of chemoradiation patients. Potentially curative resection was performed in 92, 71, and 64 % of patients treated with upfront surgery, preoperative chemotherapy, and preoperative chemoradiation, respectively. For patients treated with chemoradiation, the absence of regional lymphadenopathy on imaging was the only pretreatment variable associated with resection (odds ratio 1.77, 95 % confidence interval 1.04-3.03; p = 0.04). CONCLUSIONS: Patients treated with preoperative therapy often have more advanced disease prior to treatment initiation and therefore potential for disease progression. However, toxicity that prevents resection is rare, which is an important consideration in selecting preoperative treatment. PMID- 26868958 TI - Down-Regulation of microRNA-132 is Associated with Poor Prognosis of Colorectal Cancer. AB - BACKGROUND: Given the role of microRNA in colorectal cancer (CRC) progression, we explored the association between microRNA (miRNA) expression and CRC-related prognosis. METHODS: Three types of tissue samples (primary CRC lesions without liver metastasis, primary lesions with liver metastasis, and liver metastatic tissues) were used for miRNA profiling to identify differentially expressed miRNA. Quantitative real-time PCR was used to examine miRNA expression in CRC cells and in tumor tissues. RESULTS: MiR-132 was significantly down-regulated in primary CRC tissues with liver metastasis and liver metastatic lesions compared to primary lesions without liver metastasis. Multivariate analysis for overall survival indicated that low miR-132 expression was an independent prognostic factor for CRC patients (overall survival P = 0.040, disease-free survival P = 0.015). Ectopic expression of miR-132 significantly inhibited cell proliferation and cell invasion. The luciferase reporter assay revealed that anoctamin 1 (ANO1) was a direct target of miR-132. Kaplan-Meier survival curves showed that high ANO1 expression was a significant prognostic factor for overall survival of patients with CRC (P = 0.0344). CONCLUSIONS: Down-regulation of miR-132 is associated with poor prognosis in CRC. ANO1 could be one of the crucial targets of miR-132 in CRC. PMID- 26868959 TI - Intraretinal Hyperreflective Foci in Acquired Vitelliform Lesions of the Macula: Clinical and Histologic Study. AB - PURPOSE: To describe the natural course, visual outcomes, and anatomic changes and provide histologic correlates in eyes with intraretinal hyperreflective foci associated with acquired vitelliform lesions. DESIGN: Retrospective cohort study and imaging-histology correlation in a single donor eye. METHODS: participants: Patients with intraretinal hyperreflective foci and acquired vitelliform lesions from 2 tertiary referral centers were evaluated from January 2002 to January 2014. MAIN OUTCOME MEASURES: The chronology of clinical and imaging features of retinal anatomic changes and the pattern of intraretinal hyperreflective foci migration were documented using spectral-domain optical coherence tomography (OCT). One donor eye with intraretinal hyperreflective foci was identified in a pathology archive by ex vivo OCT and was studied with high-resolution light and electron microscopic examination. RESULTS: Intraretinal hyperreflective foci were associated with acquired vitelliform lesions in 25 of 254 eyes (9.8%) with a strong female preponderance (86% of patients). Focal disruptions to the ellipsoid zone and external limiting membrane overlying the acquired vitelliform lesions were observed prior to the occurrence of intraretinal hyperreflective foci in 75% of cases. Histologic evaluation showed that intraretinal hyperreflective foci represent cells of retinal pigment epithelium origin that are similar to those found in the vitelliform lesions themselves and contain lipofuscin granules, melanolipofuscin granules, and melanosomes. The occurrence of intraretinal hyperreflective foci was not a significant determinant of final visual acuity (P = .34), but development of outer retinal atrophy was (P = .003). CONCLUSIONS: Intraretinal hyperreflective foci associated with acquired vitelliform lesions are of retinal pigment epithelium origin, and the natural course and functional changes are described. PMID- 26868960 TI - Normal weight dyslipidemia: Is it all about the liver? AB - OBJECTIVE: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. METHODS: PubMed was searched using the following keywords: nonobese, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. RESULTS: NWD and NAFLD without obesity share a similar abnormal metabolic profile. When compared with patients with NAFLD who have obesity, the metabolic abnormalities of NAFLD without obesity are similar or less severe. Furthermore, hepatic lesions develop independent of obesity, and the extent of dyslipidemia seems comparable. CONCLUSIONS: NAFLD may impair hepatic lipid handling, causing faulty lipid homeostasis, and serves as a likely starting point for initiation and propagation of dyslipidemia along with associated comorbidities in patients without obesity. PMID- 26868961 TI - Digital approach to planning computer-guided surgery and immediate provisionalization in a partially edentulous patient. AB - This report describes a digital approach for computer-guided surgery and immediate provisionalization in a partially edentulous patient. With diagnostic data obtained from cone-beam computed tomography and intraoral digital diagnostic scans, a digital pathway of virtual diagnostic waxing, a virtual prosthetically driven surgical plan, a computer-aided design and computer-aided manufacturing (CAD/CAM) surgical template, and implant-supported screw-retained interim restorations were realized with various open-architecture CAD/CAM systems. The optional CAD/CAM diagnostic casts with planned implant placement were also additively manufactured to facilitate preoperative inspection of the surgical template and customization of the CAD/CAM-fabricated interim restorations. PMID- 26868962 TI - Accuracy of a CAD/CAM-guided template for locating abutment screws for cement retained implant-supported restorations. AB - STATEMENT OF PROBLEM: The accuracy of computer-assisted design and computer assisted manufacturing (CAD/CAM) screw channel drilling guide for locating the abutment screw has not been demonstrated. PURPOSE: The purpose of this in vitro study was to evaluate the accuracy of a CAD/CAM guide for drilling the screw access channel in angled implants. MATERIAL AND METHODS: Eighteen students prepared screw access channels through the crowns and abutments of implants placed at 0-, 15-, and 30-degree angulations in the mandibular second molar on dental casts. Experimental and control groups differed in the use of a CAD/CAM screw channel drilling guide, and each group was subdivided according to implant angulation. The accuracy of the screw channel was evaluated with regard to position and angle. Surface and volume losses of crowns and abutments were used to evaluate damage to the implanted prostheses. Statistical significance was assessed using 2-way analysis of variance (ANOVA), followed by the Tukey honestly significant difference (HSD) test (alpha=.05). RESULTS: The implant angulation significantly influenced the effect of the drilling guide with regard to the accuracy of the screw channel (F=8.319, P<.001) and crown volume loss (F=4.474, P=.014). For the 30-degree angulation, the guided drilling group exhibited smaller screw access holes than the freehand drilling group (P<.001), whereas no statistical differences were found between the groups for the 0- or 15-degree angulation. Guided drilling groups showed smaller standard lateral deviations than the freehand drilling groups. No significant differences were found in abutment volume loss among the groups. CONCLUSIONS: A CAD/CAM guide significantly enhanced the accuracy of drilling the screw channel and reduced damage to the crown and abutment, particularly at an implant angulation of 30 degrees. PMID- 26868963 TI - Effect of fiber posts on the fracture resistance of endodontically treated anterior teeth with cervical cavities: An in vitro study. AB - STATEMENT OF PROBLEM: How the placement of fiber posts affects the fracture resistance of endodontically treated maxillary central incisors with cervical cavities is not well documented. PURPOSE: The purpose of this in vitro study was to evaluate the effect of fiber posts on the fracture resistance of endodontically treated maxillary central incisors with cervical cavities. MATERIAL AND METHODS: Fifty extracted human maxillary central incisors were selected and divided into 5 test groups (n=10) according to the restoration strategy: GHT, control group; endodontically treated teeth (ETT) without endodontic posts; GCV, ETT with cervical cavities simulating coronal destruction; GCF, ETT with cervical cavities and carbon fiber posts; GGF, ETT with cervical cavities and glass fiber posts; and GCP, ETT with cervical cavities and composite resin posts. After the fiber posts had been cemented with a resin cement and the foundations had been placed, all specimens were quasi statically loaded at 45 degrees in a universal testing machine until fracture. All specimens were evaluated for fracture modes. The data were then analyzed by 1-way ANOVA, followed by multiple comparisons with the Tukey HSD test (alpha=.05). The mode of failure was determined by visual inspection. RESULTS: The mean +/-SD failure loads for the groups ranged from 718.2 +/-89.8 N to 943.8 +/-93.1 N. In a 1-way ANOVA followed by post hoc testing, GGFs had a higher fracture strength than all other groups (P<=.05). However, GCPs had a lower fracture strength than all other groups. Statistically significant differences were observed among groups (P<=.05), except between the GHT group and the GCF and GGF groups (P=.075, P=.226). All groups except GHT showed complete favorable fracture mode within the cervical third of the roots. CONCLUSIONS: Within the limitations of this in vitro study, placement of glass fiber posts significantly improved the fracture resistance of endodontically treated maxillary central incisors with cervical cavities. PMID- 26868964 TI - Outcome of zirconia partial fixed dental prostheses made by predoctoral dental students: A clinical retrospective study after 3 to 7 years of clinical service. AB - STATEMENT OF PROBLEM: Zirconia has an established role in fixed prosthodontics, especially for single crowns. Whether it is durable enough for fixed dental prostheses (FDPs) in the long term is yet unclear. PURPOSE: The purpose of this retrospective study was to evaluate the outcome of FDPs made by predoctoral students after 3 to 7 years of clinical service. MATERIAL AND METHODS: A total of 102 patients received 120 zirconia FDPs (range, 3-12 units; mean, 4.5 units) between 2007 and 2010. Materials used were Zirkonzahn Zirconia (Zirkonzahn), NobelProcera Zirconia (Nobel Biocare), and Prettau Zirconia (Zirkonzahn). Veneering porcelain was hand-layered on Zirkonzahn Zirconia (GC Initial Zr; GC Europe) and Nobel Procera Zirconia (VITA VM 9; VITA Zahnfabrik). Prettau Zirconia was monolithic and had no veneering porcelain. Success and survival rates were calculated using Kaplan-Meier survival analysis. Ethics approval was obtained from the Ethical Committee of the Northern Ostrobothnia Hospital District (100/2013). RESULTS: The 76 participants examined (75%) had received 88 zirconia FDPs. The mean follow-up period was 4.9 years (range, 3-7 years). The most common complication was chipping of the veneering porcelain in 13 of 88 FDPs (14.7%). The success rate of the zirconia-based partial FDPs after 4.9 years was 89%, and the survival rate was 100%. CONCLUSIONS: The success rate of the zirconia-based partial FDPs after 4.9 years was 89%, and the survival rate was 100%. PMID- 26868965 TI - Randomized clinical trial of the influence of impression technique on the fabrication of cast metal posts. AB - STATEMENT OF PROBLEM: Direct and indirect techniques are used for intracanal impression and fabrication of cast metal posts. However, whether those techniques affect the accuracy of cast metal posts is unknown. PURPOSE: The purpose of this randomized clinical trial was to evaluate the accuracy of cast metal posts depending on tooth position and impression technique. MATERIAL AND METHODS: Endodontically treated teeth (anterior or posterior) planned to receive cast metal posts and complete crowns were randomized according to impression technique (direct or indirect). Impressions were made by 2 operators, and time for the impression was recorded. All impressions and cast metal posts were photographed to assess any possible differences between techniques in length of the cast metal post. RESULTS: All cast metal posts were shorter than the impressions. The mean reduction for the metal posts was 2.3% for direct in anterior teeth, 5.7% for direct in posterior teeth, 6.3% for indirect in anterior teeth, and 7.2% for indirect in posterior teeth (all P<.05). Statistically significant differences were found between time of technique and tooth position (P=.031), with the direct technique more time consuming than the indirect technique (P<.001) for both tooth positions. For the indirect technique, the impression times for both tooth groups were similar (P=.459). CONCLUSIONS: Both of the intracanal impression techniques resulted in cast posts that were shorter than the impressed post space. The discrepancy was greatest for the indirect technique. Nevertheless, all posts were considered clinically acceptable and were cemented. PMID- 26868966 TI - Analysis of the relation between health statistics and eating habits in Japanese prefectures using fuzzy robust regression model. AB - In recent years, the Japanese Ministry of Health, Labour, and Welfare is working to improve citizen's lifestyle and social environment to improve their health. This is because of the following reasons. Diseases related to lifestyle such as malignant neoplasms, heart disease, and cerebrovascular disease account for about 60% of the deaths in 2013. In addition, 32% of all medical expenditures are made on lifestyle-related disease. Lifestyle-related diseases can be prevented by daily exercise, a well-balanced diet, and not smoking. This ministry is promoting measures such as dietary education, physical activity, and exercise. Improvement of diet is the easiest way to reduce the occurrence of lifestyle-related diseases. Thus, in this paper, we analyze the relation between health and diet using our fuzzy robust regression model. PMID- 26868967 TI - Lead-free 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 nanowires for energy harvesting. AB - Lead-free piezoelectric nanowires (NWs) show strong potential in sensing and energy harvesting applications due to their flexibility and ability to convert mechanical energy to electric energy. Currently, most lead-free piezoelectric NWs are produced through low yield synthesis methods and result in low electromechanical coupling, which limit their efficiency as energy harvesters. In order to alleviate these issues, a scalable method is developed to synthesize perovskite type 0.5Ba(Zr0.2Ti0.8)O3-0.5(Ba0.7Ca0.3)TiO3 (BZT-BCT) NWs with high piezoelectric coupling coefficient. The piezoelectric coupling coefficient of the BZT-BCT NWs is measured by a refined piezoresponse force microscopy (PFM) testing method and shows the highest reported coupling coefficient for lead-free piezoelectric nanowires of 90 +/- 5 pm V(-1). Flexible nanocomposites utilizing dispersed BZT-BCT NWs are fabricated to demonstrate an energy harvesting application with an open circuit voltage of up to 6.25 V and a power density of up to 2.25 MUW cm(-3). The high electromechanical coupling coefficient and high power density demonstrated with these lead-free NWs produced via a scalable synthesis method shows the potential for high performance NW-based devices. PMID- 26868968 TI - Sex differences in the outcome of juvenile social isolation on HPA axis function in rats. AB - Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine reactivity to stress, plasticity and emotionality in a sexually dimorphic manner. PMID- 26868969 TI - Involvement of dorsal striatal alpha1-containing GABAA receptors in methamphetamine-associated rewarding memories. AB - Rewarding memories induced by addictive drugs may contribute to persistent drug seeking behaviors, which is an important contributing factor to drug addiction. However, the biological mechanisms underlying drug-associated rewarding memories have not yet been fully understood, especially the new synthetic drugs, such as amphetamine-type stimulants (ATS). In this study, using the rat-conditioned place preference (CPP) model, a classic animal model for the reward-associated effects of addictive drugs, we found that the expression level of GABAA alpha1 subunits was significantly decreased in the dorsal striatum (Dstr) after conditioned methamphetamine (METH) pairing, and no significant differences were observed in the other four rewarding memory-associated areas (medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala (Amy), and dorsal hippocampus (DH)). Intra-Dstr injection of either the GABAA receptor agonist muscimol or the specific alpha1GABAA receptor-preferring benzodiazepine (BDZ) agonist zolpidem significantly abolished METH CPP formation. Thus, this study extends previous findings by showing that GABAA receptors, particularly the alpha1-containing GABAA receptors, may be strongly implicated in METH-associated rewarding memories. This work provides us with a new perspective on the goal of treating ATS addiction. PMID- 26868971 TI - Heterogeneous expression of extracellular matrix molecules in the red nucleus of the rat. AB - Previous studies in our laboratory showed that the organization and heterogeneous molecular composition of extracellular matrix is associated with the variable cytoarchitecture, connections and specific functions of the vestibular nuclei and two related areas of the vestibular neural circuits, the inferior olive and prepositus hypoglossi nucleus. The aim of the present study is to reveal the organization and distribution of various molecular components of extracellular matrix in the red nucleus, a midbrain premotor center. Morphologically and functionally the red nucleus is comprised of the magno- and parvocellular parts, with overlapping neuronal population. By using histochemical and immunohistochemical methods, the extracellular matrix appeared as perineuronal net, axonal coat, perisynaptic matrix or diffuse network in the neuropil. In both parts of the red nucleus we have observed positive hyaluronan, tenascin-R, link protein, and lectican (aggrecan, brevican, versican, neurocan) reactions. Perineuronal nets were detected with each of the reactions and the aggrecan showed the most intense staining in the pericellular area. The two parts were clearly distinguished on the basis of neurocan and HAPLN1 expression as they have lower intensity in the perineuronal nets of large cells and in the neuropil of the magnocellular part. Additionally, in contrast to this pattern, the aggrecan was heavily labeled in the magnocellular region sharply delineating from the faintly stained parvocellular area. The most characteristic finding was that the appearance of perineuronal nets was related with the neuronal size independently from its position within the two subdivisions of red nucleus. In line with these statements none of the extracellular matrix molecules were restricted exclusively to the magno- or parvocellular division. The chemical heterogeneity of the perineuronal nets may support the recently accepted view that the red nucleus comprises more different populations of neurons than previously reported. PMID- 26868970 TI - Neuropeptide Y signaling in the dorsal raphe nucleus inhibits male sexual behavior in mice. AB - Animals change their biological activities depending on their nutritional state. Reproductive functions, including sexual behavior, are suppressed under low energy conditions; however, the underlying neuronal mechanism is poorly understood. Neuropeptide Y (NPY) is an orexigenic molecule released in response to low-energy conditions and has an inhibitory effect on sexual behavior. We examined how NPY is involved in energy state-dependent regulation of male sexual behavior. Mounting, intromission, and ejaculation were evaluated as parameters of sexual behavior. Almost all parameters indicated that fasting for 24h suppressed male sexual behavior. Intracerebroventricular injection of NPY inhibited sexual behavior in males that free-fed for 8h following 24-h fasting (fed males). We next examined whether the dorsal raphe nucleus (DRN), in which serotonergic (5 HT) neurons are distributed, is involved in NPY-mediated inhibition of male sexual behavior. NPY-positive processes immunoreactive for a presynaptic marker, synaptophysin, were distributed in the DRN of both fed and fasted males. Expression of the NPY Y1 receptor in 5-HT neurons was also observed. Direct injection of NPY or 8-OH-DPAT (a 5-HT1A receptor agonist that inhibits the activity of 5-HT neurons) into the DRN inhibited male sexual behavior in fed males. In contrast, injection of BIBP-3226, a NPY Y1 receptor antagonist, or (+) DOI hydrochloride (DOI), a 5-HT2A/2C receptor agonist that activates 5-HT neurons, into the DRN partially recovered male sexual behavior in 24-h fasted males. These results suggest that NPY inhibits serotonergic neuronal activity via the Y1 receptor in the DRN, resulting in suppression of male sexual behavior in low-energy conditions. PMID- 26868972 TI - Prostaglandin E2-mediated upregulation of neuroexcitation and persistent tetrodotoxin-resistant Na(+) currents in Ah-type trigeminal ganglion neurons isolated from adult female rats. AB - Prostaglandin-E2 (PGE2) is a very important inflammatory mediator and PGE2 mediated neuroexcitation in sex-specific distribution of Ah-type trigeminal ganglion neurons (TGNs) isolated from adult female rats is not fully addressed. The whole-cell patch-clamp experiment was performed to verify the effects of PGE2, forskolin, and GPR30-selective agonist (G-1) on action potential (AP) and tetrodotoxin-resistant (TTX-R) Na(+) currents in identified Ah-type TGNs. The results showed that the firing frequency was increased in Ah- and C-types by PGE2, which was simulated by forskolin and inhibited by Rp-cyclic adenosine monophosphate (cAMP), while G-1 mimicked this effect only in Ah-types, which was abolished by GPR30-selective antagonist (G-15). Although the amplitude of AP was increased in Ah- and C-types, increased maximal upstroke velocity was confirmed only in Ah-types, suggesting distinct alternations in current density and/or voltage-dependent property of Na(+) channels. With 1.0 MUM PGE2, TTX-R Na(+) currents were upregulated without changing the current-voltage relationship and voltage-dependent activation in C-types, however, the TTX-R Na(+) current was augmented in Ah-types, peaked voltage and the voltage-dependent activation were both shifted toward hyperpolarized direction with faster slope. Intriguingly, the low-threshold persistent TTX-R component was activated from -60 mV and increased almost double at -30 mV compared with ~30-40% increment of TTX-R component being activated at ~-10 mV. Additionally, the change in TTX-R component of Ah-types was equivalent well with that in C-type TGNs. Taken these data together, we conclude that PGE2 modulates the neuroexcitation via cAMP-mediated upregulation of TTX-R Na(+) currents in both cell-types with hormone-dependent feature, especially persistent TTX-R Na(+) currents in sex-specific distribution of myelinated Ah type TGNs. PMID- 26868973 TI - Mutations of glucocerebrosidase gene and susceptibility to Parkinson's disease: An updated meta-analysis in a European population. AB - This meta-analysis aims to investigate the association between mutations of glucocerebrosidase (GBA) gene and susceptibility to Parkinson's disease (PD) in a European population. Several electronic databases were extensively searched. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association. In total, fourteen published papers screening L444P, N370S and other GBA variants were identified. The GBA mutations were significantly associated with PD in the European population. Subgroup analysis stratified by the age of onset (AAO) revealed that the association between GBA mutations and PD existed in the patients with age at onset ?50 years but did not exist in the patients with age at onset >50 years. Furthermore, the associations between N370S, and L444P with PD were also analyzed to explore the roles of the two most frequent GBA mutations in the development of PD. The results showed that significant associations between N370S, and L444P with PD were observed, respectively. Overall, the study supported that GBA mutations were a risk factor for PD in the European population. Patients with early-onset were more likely to carry GBA mutations than those with late-onset. Moreover, both L444P and N370S were associated with increased PD risk. PMID- 26868974 TI - Midline thalamic reuniens lesions improve executive behaviors. AB - The role of the thalamus in complex cognitive behavior is a topic of increasing interest. Here we demonstrate that lesions of the nucleus reuniens (NRe), a midline thalamic nucleus interconnected with both hippocampal and prefrontal circuitry, lead to enhancement of executive behaviors typically associated with the prefrontal cortex. Rats were tested on four behavioral tasks: (1) the combined attention-memory (CAM) task, which simultaneously assessed attention to a visual target and memory for that target over a variable delay; (2) spatial memory using a radial arm maze, (3) discrimination and reversal learning using a touchscreen operant platform, and (4) decision-making with delayed outcomes. Following NRe lesions, the animals became more efficient in their performance, responding with shorter reaction times but also less impulsively than controls. This change, combined with a decrease in perseverative responses, led to focused attention in the CAM task and accelerated learning in the visual discrimination task. There were no observed changes in tasks involving either spatial memory or value-based decision making. These data complement ongoing efforts to understand the role of midline thalamic structures in human cognition, including the development of thalamic stimulation as a therapeutic strategy for acquired cognitive disabilities (Schiff, 2008; Mair et al., 2011), and point to the NRe as a potential target for clinical intervention. PMID- 26868975 TI - Regulation of functional KCNQ1OT1 lncRNA by beta-catenin. AB - Long noncoding RNAs (lncRNAs) have been implicated in many biological processes through epigenetic mechanisms. We previously reported that KCNQ1OT1, an imprinted antisense lncRNA in the human KCNQ1 locus on chromosome 11p15.5, is involved in cis-limited silencing within an imprinted KCNQ1 cluster. Furthermore, aberration of KCNQ1OT1 transcription was observed with a high frequency in colorectal cancers. However, the molecular mechanism of the transcriptional regulation and the functional role of KCNQ1OT1 in colorectal cancer remain unclear. Here, we show that the KCNQ1OT1 transcriptional level was significantly increased in human colorectal cancer cells in which beta-catenin was excessively accumulated in the nucleus. Additionally, overexpression of beta-catenin resulted in an increase in KCNQ1OT1 lncRNA-coated territory. On the other hand, knockdown of beta-catenin resulted in significant decrease of KCNQ1OT1 lncRNA-coated territory and an increase in the mRNA expression of the SLC22A18 and PHLDA2 genes that are regulated by KCNQ1OT1. We showed that beta-catenin can promote KCNQ1OT1 transcription through direct binding to the KCNQ1OT1 promoter. Our evidence indicates that beta-catenin signaling may contribute to development of colorectal cancer by functioning as a novel lncRNA regulatory factor via direct targeting of KCNQ1OT1. PMID- 26868976 TI - Evaluating mitochondrial autophagy in the mouse heart. AB - Mitochondrial autophagy plays an important role in mediating mitochondrial quality control. Evaluating the extent of mitochondrial autophagy is challenging in the adult heart in vivo. Keima is a fluorescent protein that emits different colored signals at acidic and neutral pHs. Keima targeted to mitochondria (Mito Keima) is useful in evaluating the extent of mitochondrial autophagy in cardiomyocytes in vitro. In order to evaluate the level of mitochondrial autophagy in the heart in vivo, we generated adeno-associated virus (AAV) serotype 9 harboring either Mito-Keima or Lamp1-YFP. AAV9-Mito-Keima and AAV9 Lamp1-YFP were administered intravenously and mice were subjected to either forty eight hours of fasting or normal chow. Thin slices of the heart prepared within cold PBS were subjected to confocal microscopic analyses. The acidic dots Mito Keima elicited by 561nm excitation were co-localized with Lamp1-YFP dots (Pearson's correlation, 0.760, p<0.001), confirming that the acidic dots of Mito Keima were localized in lysosomes. The area co-occupied by Mito-Keima puncta with 561nm excitation and Lamp1-YFP was significantly greater 48h after fasting. Electron microscopic analyses indicated that autophagosomes containing only mitochondria were observed in the heart after fasting. The mitochondrial DNA content and the level of COX1/GAPDH, indicators of mitochondrial mass, were significantly smaller in the fasting group than in the control group, consistent with the notion that lysosomal degradation of mitochondria is stimulated after fasting. In summary, the level of mitochondrial autophagy in the adult heart can be evaluated with intravenous injection of AAV-Mito-Keima and AAV-Lamp1-YFP and confocal microscopic analyses. PMID- 26868977 TI - Current Resources for Evidence-Based Practice, March/April 2016. PMID- 26868978 TI - Innovation in capacity building of primary-care physicians in diabetes management in India: a new slant in medical education. PMID- 26868979 TI - Dynamic Permutational Isomerism in a closo-Cluster. AB - Permutational isomers of trigonal bipyramidal [W2RhIr2(CO)9(eta(5)-C5H5)2(eta(5) C5HMe4)] result from competitive capping of either a W2Ir or a WIr2 face of the tetrahedral cluster [W2Ir2(CO)10(eta(5)-C5 H5)2] from its reaction with [Rh(CO)2(eta(5)-C5HMe4)]. The permutational isomers slowly interconvert in solution by a cluster metal vertex exchange that is proposed to proceed by Rh-Ir and Rh-W bond cleavage and reformation, and via the intermediacy of an edge bridged tetrahedral transition state. The permutational isomers display differing chemical and physical properties: replacement of CO by PPh3 occurs at one permutational isomer only, while the isomers display distinct optical power limiting behavior. PMID- 26868980 TI - Evolution of the microtubular cytoskeleton (flagellar apparatus) in parasitic protists. AB - The microtubular cytoskeleton of most single-celled eukaryotes radiates from an organizing center called the flagellar apparatus, which is essential for locomotion, feeding and reproduction. The structure of the flagellar apparatus tends to be conserved within diverse clades of eukaryotes, and modifications of this overall structure distinguish different clades from each other. Understanding the unity and diversity of the flagellar apparatus provides important insights into the evolutionary history of the eukaryotic cell. Diversification of the flagellar apparatus is particularly apparent during the multiple independent transitions to parasitic lifestyles from free-living ancestors. However, our understanding of these evolutionary transitions is hampered by the lack of detailed comparisons of the microtubular root systems in different lineages of parasitic microbial eukaryotes and those of their closest free-living relatives. Here we help to establish this comparative context by examining the unity and diversity of the flagellar apparatus in six major clades containing both free-living lineages and endobiotic (parasitic and symbiotic) microbial eukaryotes: stramenopiles (e.g., Phytophthora), fornicates (e.g., Giardia), parabasalids (e.g., Trichomonas), preaxostylids (e.g., Monocercomonoides), kinetoplastids (e.g., Trypanosoma), and apicomplexans (e.g., Plasmodium). These comparisons enabled us to address some broader patterns associated with the evolution of parasitism, including a general trend toward a more streamlined flagellar apparatus. PMID- 26868981 TI - Inactivation of the cytosolic and mitochondrial serine hydroxymethyl transferase genes in Leishmania major. AB - Leishmania has two serine hydroxylmethyl transferase (SHMT) genes, one coding for a cytosolic and the other for a mitochondrial enzyme. Trypanosoma cruzi has only the gene coding for the cytosolic enzyme and Trypanosoma brucei has no SHMT. We tested whether these genes were dispensable for growth in Leishmania major. By gene inactivation we succeeded in generating three cells lines one without the cytosolic cSHMT, one without the mitochondrial mSHMT, and finally one L. major line without any SHMT. SHMT is thus dispensable for growth of Leishmania in rich medium. The ability of the various shmt null mutants to grow in defined medium was tested and the growth of the shmt null mutant was dependent on the presence of serine. Overall this work has shown that SHMT is dispensable for Leishmania growth but it may be necessary when growing in environments poor in serine. PMID- 26868983 TI - Lying, misery and illness: Towards a medical anthropology of the lie. PMID- 26868982 TI - Genetic associations between maternal traits and aggressive behaviour in Large White sows. AB - The present study examined the possibilities and consequences of selecting pigs for reduced aggression and desirable maternal behaviour. Data were recorded from 798 purebred Large White gilts, with an age of 217+/-17.7 (mean+/-SD) days, which were observed at mixing with unfamiliar conspecifics. The reaction of the sows towards separation from their litter was assessed for 2022 litters from 848 Large White sows. Sows' performance during their time in the farrowing unit was scored based on the traits farrowing behaviour (i.e. need of birth assistance), rearing performance (i.e. litter quality at day 10 postpartum (pp)), usability (i.e. additional labour input during lactation period e.g. for treatments) and udder quality of the sow (i.e. udder attachment). For agonistic behaviour, traits heritabilities of h 2=0.11+/-0.04 to h 2=0.28+/-0.06 were estimated. For the sow's reaction towards separation from her litter low heritabilities were found (h 2=0.03+/-0.03 for separation test on day 1 pp and h 2=0.02+/-0.03 for separation test on day 10 pp). Heritabilities for lactating sow's performance (farrowing behaviour, rearing performance, usability of the sow and udder quality) in the farrowing unit ranged from h 2=0.03+/-0.02 to h 2=0.19+/-0.03. Due to these results it can be assumed that selection for these traits, for example, for udder quality or reduced aggression, is possible. Antagonistic associations were found between separation test on day 1 pp and different measures of aggressiveness (r g =-0.22+/-0.26 aggressive attack and r g =-0.41+/ 0.33 reciprocal fighting). Future studies should determine economic as well as welfare-related values of these traits in order to decide whether selection for these traits will be reasonable. PMID- 26868984 TI - Inventing a new death and making it believable. AB - This article shows how the concept of 'brain death' was created in order that the routinization of solid organ transplantation could take place. The concept permitted individuals diagnosed as brain-dead but whose respiration and heartbeat continued through technological assistance to be counted as no longer alive, and therefore organs could be retrieved from them without legal reprisals. It is shown how, because the condition of brain-dead bodies is ambiguous--they are at once dead and alive--discursive practices must be put to work in both medicine and law to justify their status as dead. Despite an apparent consensus within the medical world about the concept of brain death, disagreement remains among various countries about how best to make the diagnosis. Moreover, professionals working with brain-dead patients draw on a Cartesian split between mind and body in order to allow themselves to count such patients as dead; this maneuver is justified because the minds of brain-dead patients no longer function, although their bodies clearly remain very much alive. Without the legal fiction of brain death the transplant world would be severely hampered. PMID- 26868985 TI - Lying, secrecy and power within the doctor-patient relationship. AB - Based on ethnographic research from two distinct French settings, the author examines the lying of doctors, and the lying of patients. The first situation is that of medical practitioners, specialists in the treatment of alcoholism, who affirm to ex-drinkers that it is impossible to drink normally again after treatment, without falling back into dependency, whilst knowing of the existence of contradictory cases. The second situation is that in which a certain number of patients find themselves, and who lead their doctors to believe that they have been taking their medication and dissimulate their real behaviour, that of non observance of prescription. The author argues that lying, in the context of secrecy, is the expression of and the indication of a power relationship. Moreover, the rationalisation that accompanies the lie does not stop it from producing effects in contradiction to its motivation, thus exposing the conflict between therapeutic logic and social logic: the paradoxical character of lying. PMID- 26868986 TI - Theatres of the lie: 'crazy' deception and lying as drama. AB - In this article, the author argues that lying is drama, theatre, which brings about transition, reflection, reversal and involvement of the participants in the drama. By means of ethnographic data of a psychiatric ward, the author shows that lying of mental patients is not pathological, but a ritual of affliction. By using Turner's theory about rituals and performance and Goffman's theory about presentation of the self it will be showed that lying serves the redefinition of reciprocity and solidarity. With the help of Bakhtin's work on Rabelais, the author discusses the nature of the drama of the lie. It is concluded that a perspective on lying as theatre may be of use outside psychiatric wards and will occur in imbalanced power relationships. PMID- 26868987 TI - Disease or deception: Munchausen by Proxy as a weapon of the weak. AB - This paper aims to trouble certain assumptions about the clinical nature of Munchausen by Proxy (MBP), which has been described in the medical literature as a rare "culture bound syndrome" having surfaced at a particular moment, late modernity, and in a particular "place", Europe and North America and their extensions. At the heart of this disorder is a lie perpetrated by disturbed mothers who masquerade as the concerned and anxious caretakers of one or more long-suffering children who are plagued by fictive or maternally-incited illnesses and, in the worst instance, who are subjected to death by maternal design. MBP is positioned within a broader comparative context as an extreme pole along a continuum of (mal-) adaptive maternal behaviors in response to unrecognized and unmet needs, not all of which are pathological. Second, the locus of the pathology is expanded to include not only the disturbed and troubled mother-child dyad, but also the relationship between mother and her doctors and other caregivers and protectors. In these medicalized transactions - shot through with power, love, and pain - the child emerges as an almost incidental or "transitional object", a mere pretext that gives voice and substance to the adults' (mothers' and professionals') narcissistic needs. Finally, the social and moral uses of illness as drama, performance, and pageantry, and as a passively aggressive "weapon of the weak", are identified as a key structure of MBP disease. Based on decades of research on maternal thinking and practice (often under extreme conditions) the paper is an attempt to demonstrate what a "critically applied and cross-cultural medical anthropology" can add to the clinical picture and to a broader social understanding of this seemingly bizarre, rare, and contested syndrome. PMID- 26868988 TI - Gade deceptions and lies told by the ill: The Caribbean sociocultural construction of truth in patient-healer encounters. AB - A constructivist approach in medical anthropology suggests that the boundary between lies and truth in sickness narratives is thin. Based on fieldwork in the French (Martinique) and English (Saint-Lucia) Carribbean with gade and quimboiseurs (local folk healers), this paper addresses the gap between naive romanticism and radical cynicism in the anthropological analysis of patient healer encounters. Is the sick person lying when she accuses evil spirits for her behaviour or sickness? Is the quimboiseur who is building a meaningful explanation or diagnosis simply a liar taking advantage of his client's credulity? The challenge for anthropology is not to determine whether or not a person is lying when attributing their ill fortune to witchcraft. Instead, in this paper, the author approaches lying as a language-game played by both patients and folk healers. Concepts of lying as games, tactical lies, pragmatic creativity, and constructive lies are introduced here as a perspective for a reconsideration of lying as a pertinent research object. PMID- 26868990 TI - Memoriam: Roy Porter (1946-2002). PMID- 26868991 TI - Short-term hypothermic preservation of human testicular tissue: the effect of storage medium and storage period. AB - OBJECTIVE: To optimize the storage medium and period during short-term preservation of human testicular tissue. DESIGN: First, human testicular tissue fragments from five patients were kept at 4 degrees C for 3 days in different media (Dulbecco's modified Eagle's medium [DMEM]/F12, DMEM/F12 + 20% human serum albumin [HSA], DMEM/F12 + 50% HSA, and HSA). Secondly, fragments from four patients were kept in DMEM/F12 for 3, 5, or 8 days at 4 degrees C. SETTING: Laboratory research environment. PATIENT(S): Adult human testicular tissue. INTERVENTION(S): Biopsy and short-term storage of human testicular tissue at different conditions. MAIN OUTCOME MEASURE(S): Viability, general tissue morphology, Sertoli cell morphology, number of spermatogonia, and apoptosis. The experimental conditions were compared with fresh control samples. RESULT(S): Storing human testicular tissue in DMEM/F12 did not alter any of the investigated parameters. In most conditions containing HSA, tissue morphology was altered, and in all of them the Sertoli cell morphology was affected. The number of spermatogonia was only affected when tissue was stored in 100% HSA. In the second part of the study, tissue morphology deteriorated significantly as of 5 days of hypothermic storage, and Sertoli cell morphology after 8 days. CONCLUSION(S): Human testicular tissue can be preserved for 3 days at 4 degrees C in DMEM/F12 without altering tissue morphology, Sertoli cell morphology, number of spermatogonia, or number of apoptotic cells. PMID- 26868992 TI - Effects of maternal age on euploidy rates in a large cohort of embryos analyzed with 24-chromosome single-nucleotide polymorphism-based preimplantation genetic screening. AB - OBJECTIVE: To determine the effect of maternal age on the average number of euploid embryos retrieved during oocyte harvest as part of an in vitro fertilization (IVF) cycle, including the probability of retrieving at least one euploid embryo in a cohort (PrE). DESIGN: Retrospective study. SETTING: Preimplantation genetic screening (PGS) laboratory. PATIENT(S): Women aged 18 to 48 years undergoing IVF treatment. INTERVENTION(S): Use of 24-chromosome single nucleotide polymorphism (SNP)-based PGS of day-3 and day-5 embryo biopsies. MAIN OUTCOME MEASURE(S): Relationships between maternal age and the rate of embryos that tested as euploid (hereafter referred to as "euploid embryos"), the average number and proportion of euploid embryos per IVF cycle, and PrE. RESULT(S): We analyzed 22,599 day-3 embryos and 15,112 day-5 embryos. In women aged 27 to 35 years, the median proportion of euploid embryos in each cycle remained constant at ~35% in day-3 biopsies and ~55% in day-5 biopsies, but it decreased rapidly after age 35. On average, women in their late 20s had four euploid embryos (day 3 or day 5) per cycle, but this number decreased linearly (R(2) >= 0.983) after 35 years of age. The effect of maternal age on PrE was similar, with a rapid exponential decline (R(2) = 0.986). Across all maternal ages, the euploid proportion and number of embryos per cycle were counterbalanced, so the number of euploid embryos per cycle was the same for day-3 and day-5 biopsies. This suggests that the loss of embryos from day 3 to day 5 was primarily due to aneuploidy. CONCLUSION(S): Our results confirm the known inverse relationship between advanced maternal age (>35 years) and embryo euploidy, demonstrating that equal numbers of euploid embryos are available at day 3 and day 5. PMID- 26868993 TI - Higher PDCD4 expression is associated with obesity, insulin resistance, lipid metabolism disorders, and granulosa cell apoptosis in polycystic ovary syndrome. AB - OBJECTIVE: To investigate the expression and clinical significance of programmed cell death 4 (PDCD4), a novel metabolism-associated gene, during polycystic ovary syndrome (PCOS) pathogenesis. DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): A total of 77 PCOS patients and 67 healthy women as matched controls. INTERVENTION(S): PDCD4 expression in peripheral blood mononuclear cells analyzed by quantitative real-time polymerase chain reaction, and apoptosis of granulosa cells (GCs) detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and small-interfering RNA. MAIN OUTCOME MEASURE(S): PDCD4 expression, body mass index (BMI), insulin 0, insulin 120, glucose 120, homeostasis model assessment for insulin resistance (HOMA-IR), homeostasis model assessment for beta-cell function (HOMA-beta), triglycerides, high-density lipoprotein (HDL), and GC apoptosis. RESULT(S): The PCOS patients had higher PDCD4 expression, but BMI was similar as matched with the obese group, which positively correlated with BMI, insulin 0, insulin 120, glucose 120, HOMA IR, HOMA-beta, triglycerides and negatively correlated with HDL (P<.05). After metformin treatment, PDCD4 expression was distinctly down-regulated for the obese women with PCOS with insulin resistance. Compared with the healthy controls, the apoptosis percentage of GCs was higher in the PCOS group and was decreased by knocking down PDCD4. Furthermore, expression of proapotosis factor Bax and the Bax/Bcl-2 ratio were lower, whereas the expression of antiapoptosis factor Bcl-2 was increased. In a multivariate logistic regression analysis, the level of PDCD4 expression independently related to the odds of PCOS risk after controlling for estradiol and insulin 120 (odds ratio 1.318). CONCLUSION(S): Our study suggests for the first time that higher PDCD4 expression might play an important role in PCOS pathogenesis by affecting obesity, insulin resistance, lipid metabolism disorders, and GC apoptosis. PMID- 26868994 TI - Discriminant analysis forecasting model of first trimester pregnancy outcomes developed by following 9,963 infertile patients after in vitro fertilization. AB - OBJECTIVE: To investigate a forecasting method developed to predict first trimester pregnancy outcomes using the first routine ultrasound scan for early pregnancy on days 27-29 after ET and to determine whether to perform a repeated scan several days later based on this forecasting method. DESIGN: Prospective analysis. SETTING: Infertile patients at an assisted reproductive technology center. PATIENT(S): A total of 9,963 patients with an early singleton pregnancy after in vitro fertilization (IVF)-ET. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ongoing pregnancy >12 weeks of gestation. RESULT(S): The classification score of ongoing pregnancy was equal to (1.57 * Maternal age) + (1.01 * Mean sac diameter) + (-0.19 * Crown-rump length) + 25.15 (if cardiac activity is present) + 1.30 (if intrauterine hematomas are present) - 47.35. The classification score of early pregnancy loss was equal to (1.66 * Maternal age) + (0.84 * Mean sac diameter) + (-0.38 * Crown-rump length) + 8.69 (if cardiac activity is present) + 1.60 (if intrauterine hematomas are present) - 34.77. In verification samples, 94.44% of cases were correctly classified using these forecasting models. CONCLUSION(S): The discriminant forecasting models are accurate in predicting first trimester pregnancy outcomes based on the first scan for early pregnancy after ET. When the predictive result is ongoing pregnancy, a second scan can be postponed until 11-14 weeks if no symptoms of abdominal pain or vaginal bleeding are present. When the predictive results suggest early pregnancy loss, repeated scans are imperative to avoid a misdiagnosis before evacuating the uterus. PMID- 26868995 TI - Potential role of circulating microRNAs as a biomarker for unexplained recurrent spontaneous abortion. AB - OBJECTIVE: To compare circulating microRNA (miRNA) profiles between unexplained recurrent spontaneous abortion (URSA) and normal early pregnancies (NEP) and to evaluate the potential role of circulating miRNA as a biomarker for URSA. DESIGN: Laboratory study using human plasma samples. SETTING: Special hospital and research institutes. PATIENT(S): From September 2012 to April 2013, samples of plasma were obtained from 27 URSA patients and 28 NEP patients at 6-10 weeks of gestation at the Department of Reproductive Immunology in Family Planning Special Hospital of Guangdong Province. INTERVENTION(S): Differential miRNA profiling analysis of plasma collected from URSA and NEP patients was performed with the use of microarray. MAIN OUTCOME MEASURE(S): The circulating miRNA expression profile was assessed by means of microarray and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. RESULT(S): Twenty five circulating miRNAs were expressed differentially in URSA compared with NEP. Of these, nine were overexpressed and 16 down-regulated. Six differentially expressed circulating miRNAs were selected to validate the microarray results, and qRT-PCR data confirmed the reliability of the microarray results. Further analysis showed that four circulating miRNAs (miR-320b, miR-146b-5p, miR-221-3p, miR-559) were up-regulated. In URSA, one circulating miRNA (miR-101-3p) was down regulated in other larger scale samples according to qRT-PCR. Based on target gene analysis, we speculate that these circulating miRNAs regulate URSA by targeting immune, apoptosis, and angiogenic gene functions. CONCLUSION(S): Circulating microRNAs may be involved in URSA pathogenesis and provide a promising new diagnostic biomarker for URSA. PMID- 26868999 TI - Differing Perspectives on Breast Cancer Chemoprevention. PMID- 26869000 TI - Differing Perspectives on Breast Cancer Chemoprevention. PMID- 26869001 TI - Clarifying Assumptions and Outcomes in Cost-effectiveness Analyses. PMID- 26869002 TI - Differing Perspectives on Breast Cancer Chemoprevention--Reply. PMID- 26869003 TI - Clarifying Assumptions and Outcomes in Cost-Effectiveness Analyses--Reply. PMID- 26869004 TI - Missing Middle Initial in Author's Name. PMID- 26869005 TI - Error in Corresponding Author Address. PMID- 26869007 TI - Modified Hydrogels to Enhance Cellular Therapy for AKI: A Translational Challenge. PMID- 26869006 TI - IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI. AB - Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI. PMID- 26869010 TI - Strigolactones: how far is their commercial use for agricultural purposes? AB - Strigolactones are a class of natural and synthetic compounds that in the past decade have been exciting the scientific community not only for their intriguing biological properties but also for their potential applications in agriculture. These applications range from their use as hormones to modify and/or manage plant architecture, to their use as stimulants to induce seed germination of parasitic weeds and thus control their infestation by a reduced seed bank, to their use as 'biostimulants' of plant root colonisation by arbuscular mycorrhizal fungi, improving plant nutritional capabilities, to other still unknown effects on microbial soil communities. More recently, these compounds have also been attracting the interest of agrochemical companies. In spite of their biological attractiveness, practical applications are still greatly hampered by the low product yields obtainable by plant root exudates, by the costs of their synthesis, by the lack of knowledge of their off-target effects and by the not yet specified or properly identified legislation that could regulate the use of these compounds, depending on the agricultural purposes. The aim of this article is to discuss, in the light of current knowledge, the different scenarios that might play out in the near future with regard to the practical application of strigolactones. (c) 2016 Society of Chemical Industry. PMID- 26869011 TI - Virgibacillus kapii sp. nov., isolated from Thai shrimp paste (Ka-pi). AB - A Gram-reaction-positive and rod-shaped bacterium, designated KN3-8-4T, was isolated from shrimp paste collected from a market in Nakhon Sri Thammarat province, Thailand. Strain KN3-8-4T was a strictly aerobic, motile bacterium that produced ellipsoidal endospores at a terminal position. The isolate grew at pH 4.5-10 (optimum pH 7.5), at 11-42 degrees C (optimum 37 degrees C) and in the presence of 0-15% (w/v) NaCl (optimum 1-5%). On the basis of 16S rRNA gene sequences, strain KN3-8-4T belonged to the genus Virgibacillus and showed highest similarity with Virgibacillus olivae JCM 30551T (97.85% 16S rRNA gene sequence similarity). The diamino acid found in the cell-wall peptidoglycan was meso diaminopimelic acid and the major isoprenoid quinone was MK-7. Strain KN3-8-4T contained anteiso-C15:0 and anteiso-C17:0 as major cellular fatty acids and had phosphatidylglycerol, diphosphatidylglycerol, two unknown phospholipids and one glycolipid as polar lipids. The DNA G+C content was 43.5 mol%. Strain KN3-8-4T showed low DNA-DNA relatedness (20.44%) with V. olivae JCM 30551T. On the basis of phenotypic and chemotaxonomic data and phylogenetic analyses, strain KN3-8-4T represents a novel species of the genus Virgibacillus for which the name Virgibacillus kapii sp. nov. is proposed. The type strain is KN3-8-4T (=JCM 30071T=LMG 28282T=TISTR 2279T=PCU 345T). PMID- 26869008 TI - Recombinant N-Terminal Slit2 Inhibits TGF-beta-Induced Fibroblast Activation and Renal Fibrosis. AB - Fibrosis and inflammation are closely intertwined injury pathways present in nearly all forms of CKD for which few safe and effective therapies exist. Slit glycoproteins signaling through Roundabout (Robo) receptors have been described to have anti-inflammatory effects through regulation of leukocyte cytoskeletal organization. Notably, cytoskeletal reorganization is also required for fibroblast responses to TGF-beta Here, we examined whether Slit2 also controls TGF-beta-induced renal fibrosis. In cultured renal fibroblasts, which we found to express Slit2 and Robo-1, the bioactive N-terminal fragment of Slit2 inhibited TGF-beta-induced collagen synthesis, actin cytoskeletal reorganization, and Smad2/3 transcriptional activity, but the inactive C-terminal fragment of Slit2 did not. In mouse models of postischemic renal fibrosis and obstructive uropathy, treatment with N-terminal Slit2 before or after injury inhibited the development of renal fibrosis and preserved renal function, whereas the C-terminal Slit2 had no effect. Our data suggest that administration of recombinant Slit2 may be a new treatment strategy to arrest chronic injury progression after ischemic and obstructive renal insults by not only attenuating inflammation but also, directly inhibiting renal fibrosis. PMID- 26869012 TI - Effects of short-term quetiapine treatment on emotional processing, sleep and circadian rhythms. AB - BACKGROUND: Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers. METHODS: Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks. RESULTS: Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times. CONCLUSIONS: These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action. PMID- 26869013 TI - Four-Duct Ligation for the Treatment of Sialorrhea in Children. AB - IMPORTANCE: The 4-duct ligation procedure has appeal for its surgical simplicity and limited invasiveness in the management of pediatric sialorrhea. However, more information is required to understand the benefits, risks, success rates, and long-term effects of this intervention. OBJECTIVES: To report the clinical outcomes of the 4-duct ligation procedure in pediatric patients diagnosed as having sialorrhea and the associated complication rates and to characterize patient and caregiver satisfaction in a consecutive series. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a retrospective cohort study at an academic tertiary pediatric center and pediatric rehabilitation hospital. Patients included 38 children with neurological impairment who underwent a 4-duct salivary gland ligation (parotid and submandibular glands) between January 1, 2004, and July 31, 2012. The dates of the analysis were August 2013 through February 2015. MAIN OUTCOMES AND MEASURES: Posttreatment assessments included duration of effect, severity and frequency of drooling before and after the procedure, patient complications, caregiver satisfaction, caregiver recommendation of the procedure, and caregiver overall assessment of the child's quality of life. Clinical and outcome measures were collected before the procedure, 1 month after the procedure, 1 year after the procedure, and at the most recent follow-up (range, 3-8 years). RESULTS: The study cohort comprised 38 participants. Their median age was 11 years (age range, 5-17 years), and 37% (14 of 38) were female. The mean (SD) duration of effect was 52.6 (20.4) months. Patients with previous sialorrhea management were more likely to demonstrate an improvement in their drooling frequency score at 1 year. Thirteen complications were documented in 12 patients. The most common complications were persistent facial swelling and aspiration pneumonia. Eighty percent (28 of 35) of caregivers reported an improvement in their child's drooling at 1 month, while 69% (25 of 36) and 71% (24 of 34) stated that there was an improvement at the 1-year follow-up and the most recent follow-up, respectively. CONCLUSIONS AND RELEVANCE: The 4-duct ligation procedure offers a simple, effective, and minimally invasive approach to the management of sialorrhea in children. PMID- 26869014 TI - Effect of rituximab on pulmonary function in patients with rheumatoid arthritis. AB - BACKGROUND: Rituximab (RTX), a B-cell depleting monoclonal antibody is increasingly used in several antibody-mediated diseases. It has been reported to cause pulmonary toxicity, though mainly during polychemotherapy of malignant lymphoma. Prospective data on RTX-induced pulmonary complications in patients with rheumatoid arthritis (RA) are lacking. METHODS AND METHODS: Serial spirometries and measurements of diffusion capacity of the lung for carbon monoxide (DLCO) in patients with RA before and 2, 4, 8, and 26 weeks after treatment with RTX were performed. A reduction from baseline of forced vital capacity (FVC) of >=10%, or >=15% of DLCO was defined as indicative for pulmonary toxicity. RESULTS: Thirty-three patients (mean (SD) age 59 (12) years, 27% males) were included. Mean (SD) FVC predicted and DLCO predicted at baseline were 108% (18%) and 88% (18%), respectively. In contrast to FVC, DLCO showed a progressive decline during follow-up with a maximum reduction of 6.1% (95%CI 2.5%, 9.7%; p = 0.001) at 26 weeks compared with baseline. After 26 weeks, 22% of the patients had a >=15% DLCO decline. None of the patients reported increased dyspnea during follow-up. Risk factors for pulmonary function changes after treatment with RTX were cigarette smoking, repeated administration of the drug, and co-medication with Prednisone. CONCLUSION: Although no cases of symptomatic lung injury were observed, the progressive DLCO decline seems to indicate the presence of subclinical RTX-induced pulmonary toxicity. PMID- 26869015 TI - Effectiveness of Computer Tailoring Versus Peer Support Web-Based Interventions in Promoting Physical Activity Among Insufficiently Active Canadian Adults With Type 2 Diabetes: Protocol for a Randomized Controlled Trial. AB - BACKGROUND: Type 2 diabetes is a major challenge for Canadian public health authorities, and regular physical activity is a key factor in the management of this disease. Given that less than half of people with type 2 diabetes in Canada are sufficiently active to meet the Canadian Diabetes Association's guidelines, effective programs targeting the adoption of regular physical activity are in demand for this population. Many researchers have argued that Web-based interventions targeting physical activity are a promising avenue for insufficiently active populations; however, it remains unclear if this type of intervention is effective among people with type 2 diabetes. OBJECTIVE: This research project aims to evaluate the effectiveness of two Web-based interventions targeting the adoption of regular aerobic physical activity among insufficiently active adult Canadian Francophones with type 2 diabetes. METHODS: A 3-arm, parallel randomized controlled trial with 2 experimental groups and 1 control group was conducted in the province of Quebec, Canada. A total of 234 participants were randomized at a 1:1:1 ratio to receive an 8-week, fully automated, computer-tailored, Web-based intervention (experimental group 1); an 8 week peer support (ie, Facebook group) Web-based intervention (experimental group 2); or no intervention (control group) during the study period. RESULTS: The primary outcome of this study is self-reported physical activity level (total min/week of moderate-intensity aerobic physical activity). Secondary outcomes are attitude, social influence, self-efficacy, type of motivation, and intention. All outcomes are assessed at baseline and 3 and 9 months after baseline with a self reported questionnaire filled directly on the study websites. CONCLUSIONS: By evaluating and comparing the effectiveness of 2 Web-based interventions characterized by different behavior change perspectives, findings of this study will contribute to advances in the field of physical activity promotion in adult populations with type 2 diabetes. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN15747108; http://www.isrctn.com/ISRCTN15747108 (Archived by WebCite at http://www.webcitation.org/6eJTi0m3r). PMID- 26869016 TI - VDR and VDBP genes polymorphisms associated with susceptibility to tuberculosis in a Han Taiwanese population. AB - BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to the activation of macrophages and the deficiency of vitamin D seems to be involved in the risk of tuberculosis (TB). The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D receptor binding protein (VDBP) may be influenced by polymorphisms in the VDR and VDBP genes. In this study, variation in the VDR and VDBP genes was investigated in a Taiwanese population with TB. METHODS: We typed four VDR polymorphisms of restriction endonuclease sites for ApaI, TaqI, BsmI, and FokI and three VDBP polymorphisms-Thr420Lys, Asp416Glu, and Cys299Cys-in 198 patients with TB and 170 healthy volunteers. RESULTS: VDR TaqI, VDR BsmI, and VDBP Asp416Glu were significantly associated with TB susceptibility. Odd ratios of risk genotypes of the above three polymorphisms were 2.16 (95% confidence interval 1.01, 4.65), 2.14 (95% confidence interval 1.06, 4.31), and 2.24 (95% confidence interval 1.04, 4.80), respectively. VDBP haplotype analysis showed Gc1f carriers associated to TB. CONCLUSION: The polymorphisms in the VDR and VDBP genes appeared to be responsible for host susceptibility to human TB in a Taiwanese population. PMID- 26869017 TI - The role of endothelial microparticles in autoimmune disease patients with Raynaud's phenomenon. AB - BACKGROUND AND AIM: Raynaud's phenomenon (RP) is a microvascular disorder characterized by episodic peripheral vasospasm and ischemia and is commonly found in patients with autoimmune diseases (AID). The vasomotor homoeostasis and endothelial cells damage are involved in RP. Endothelial microparticles (EMPs) may act as a biomarker for endothelial damage. The aim of this study is to investigate the correlation between the levels of microparticles (MPs) and microvasculopathy in AID with RP. METHODS: Thirty-seven patients with AID and RP (RP group) and 27 patients with AID but without RP (non-RP group) were enrolled. The microvasculopathy score of RP was graded by nailfold capillary microscopy. The plasma levels of MPs were measured by flow cytometry utilizing specific labels for endothelial MPs (CD105 and CD144) and annexin V staining for phosphatidylserine bearing-MPs (annexin V+MPs). RESULTS: The levels of circulating EMPs (CD105+ p = 0.005, CD144+ p = 0.004), and the annexin V+ MPs (p < 0.001) were significantly elevated in the RP group compared with the non-RP group. Moreover, the high microvasculopathy scores were closely related with annexinV+ MPs levels in the RP group (p = 0.041). CONCLUSIONS: Levels of circulating EMPs and annexin V+ MPs are elevated in AID patients with RP indicate the endothelial damage and endothelial dysfunctions. In addition, levels of annexin V+ MPs can predict the severity of microvasculopathy in AID with RP. PMID- 26869018 TI - Bioelectric modulation of macrophage polarization. AB - Macrophages play a critical role in regulating wound healing and tissue regeneration by changing their polarization state in response to local microenvironmental stimuli. The native roles of polarized macrophages encompass biomaterials and tissue remodeling needs, yet harnessing or directing the polarization response has been largely absent as a potential strategy to exploit in regenerative medicine to date. Recent data have revealed that specific alteration of cells' resting potential (Vmem) is a powerful tool to direct proliferation and differentiation in a number of complex tissues, such as limb regeneration, craniofacial patterning and tumorigenesis. In this study, we explored the bioelectric modulation of macrophage polarization by targeting ATP sensitive potassium channels (KATP). Glibenclamide (KATP blocker) and pinacidil (KATP opener) treatment not only affect macrophage polarization, but also influence the phenotype of prepolarized macrophages. Furthermore, modulation of cell membrane electrical properties can fine-tune macrophage plasticity. Glibenclamide decreased the secretion and gene expression of selected M1 markers, while pinacidil augmented M1 markers. More interestingly, glibencalmide promoted macrophage alternative activation by enhancing certain M2 markers during M2 polarization. These findings suggest that control of bioelectric properties of macrophages could offer a promising approach to regulate macrophage phenotype as a useful tool in regenerative medicine. PMID- 26869019 TI - Storage Stability of Slightly Acidic Electrolyzed Water and Circulating Electrolyzed Water and Their Property Changes after Application. AB - Slightly acidic electrolyzed water (SAEW) has been recognized as an effective bactericidal agent with free chlorine, but its limitations include its instability and its great dependence on equipment. Newly developed circulating electrolyzed water (CEW) with a higher available chlorine concentration (ACC) could successfully overcome these limitations. In this study, SAEW (ACC of 20 mg/L), CEW1 (ACC of 200 mg/L), and CEW2 (ACC of 20 mg/L) were evaluated for changes in properties (pH, oxidization reduction potential [ORP], and ACC) during storage in open or closed glass bottles under light or dark conditions at room temperature (approximately 20 degrees C) and after washing pork and lettuce. Additionally, the washed pork and lettuce were evaluated for total viable counts, pH and general appearance. The results showed that CEW1 with a higher ACC has better stability than SAEW with a lower ACC for the storage and washing experiments, and CEW still remained stable after dilution with distilled water. The property indices of EW were greatly affected for the pork-washing experiments compared with the lettuce-washing experiments, probably due to the existence of alkaline and organic materials on the surface of pork. Furthermore, EWs were more effective for inactivating microbes in lettuce than in pork, while there was no significant difference in tissue pH and the general appearance of pork and lettuce. These findings indicated that CEW with a higher ACC shows potential for reducing foodborne pathogens on pork and lettuce without effects on their physicochemical characteristics, and it can be applied in a diluted form. PMID- 26869020 TI - Two Weeks of Repeated-Sprint Training in Soccer: To Turn or Not to Turn? AB - PURPOSE: To compare the effects of 2 repeated-sprint training programs on fitness in soccer. METHODS: Fifteen semiprofessional soccer players (age: 24 +/- 4 y; body mass: 77 +/- 8 kg) completed 6 repeated-sprint training sessions over a 2 week period. Players were assigned to a straight-line (STR) (n = 8; 3-4 sets of 7 * 30 m) or change of direction (CoD) (n = 7; 3-4 sets of 7 * 20-m) repeated sprint training group. Performance measures included 5-, 10-, and 20-m sprints, countermovement jump, Illinois agility, and Yo-Yo Intermittent Recovery Test level 1 (YYIRTL1) performance. Internal (heart rate) and external (global positioning system-derived measures) training loads were monitored throughout. Data were analyzed using magnitude-based inferences. RESULTS: Internal and external loads were higher in the STR group than in the CoD group with large differences in maximum velocity (28.7%; +/-90% confidence limits, 3.3%), moderate differences in mean heart rates (7.0%; +/-1.4%) and PlayerLoad (17.6%; +/-8.6%), and small differences in peak heart rates (3.0%; +/-1.6%). Large improvements in 5-m (STR: 9.6%; +/-7.0% and CoD: 9.4%; +/-3.3%), 10-m (STR: 6.6%; +/-4.6% and CoD: 6.7%; +/-2.2%), and 20-m (STR: 3.6; +/-4.0% and CoD: 4.0; +/-1.7%) sprints were observed. Large and moderate improvements in YYIRTL1 performance were observed in the STR (24.0%; +/-9.3%) and CoD (31.0%; +/-7.5%), respectively. Between-groups differences in outcome measures were unclear. CONCLUSIONS: Two weeks of repeated-sprint training stimulates improvements in acceleration, speed, and high-intensity running performance in soccer players. Despite STR inducing higher internal and external training loads, training adaptations were unclear between training modes, indicating a need for further research. PMID- 26869022 TI - Mauritia flexuosa L. protects against deficits in memory acquisition and oxidative stress in rat hippocampus induced by methylmercury exposure. AB - OBJECTIVE: Methylmercury (MeHg) is the most toxic form of mercury that can affect humans through the food chain by bioaccumulation. Human organism is capable of triggering visual and cognitive disorders, neurodegeneration, as well as increased production of reactive species of O2 and depletion of natural anti oxidant agents. In this context, Mauritia flexuosa L., a fruit rich in compounds with anti-oxidant properties, emerged as an important strategy to prevent the MeHg damages. So, this work has aimed to elucidate the protective effect of Mauritia flexuosa L. on the damage caused by the exposure of rats to MeHg. METHODS: In order to evaluate the effect of MeHg on rat aversive memory acquisition and panic-like behavior, we have used elevated T-maze apparatus and after behavioral test, the hippocampus was removed to perfom lipid peroxidation. RESULTS: Our results demonstrated that the exposure to MeHg caused deficits in inhibitory avoidance acquisition (aversive conditioning) and in the learning process, and increased levels of lipid peroxidation in hippocampus tissue. However, the pretreatment with feed enriched with Mauritia flexuosa L. showed a protective effect against cognitive deficits caused by MeHg and also prevented the occurrence of cytoplasmic membrane damage induced by lipid peroxidation in the hippocampal region. DISCUSSION: Therefore, this study suggests that Mauritia flexuosa L. represents an important strategy to prevent neurocytotoxics and behavioral effects of MeHg. PMID- 26869021 TI - Expansion and stress responses of AP2/EREBP superfamily in Brachypodium distachyon. AB - APETALA2/ethylene-responsive element binding protein (AP2/EREBP) transcription factors constitute one of the largest and most conserved gene families in plant, and play essential roles in growth, development and stress response. Except a few members, the AP2/EREBP family has not been characterized in Brachypodium distachyon, a model plant of Poaceae. We performed a genome-wide study of this family in B. distachyon by phylogenetic analyses, transactivation assays and transcript profiling. A total of 149 AP2/EREBP genes were identified and divided into four subfamilies, i.e., ERF (ethylene responsive factor), DREB (dehydration responsive element binding gene), RAV (related to ABI3/VP) and AP2. Tandem duplication was a major force in expanding B. distachyon AP2/EREBP (BdAP2/EREBP) family. Despite a significant expansion, genomic organizations of BdAP2/EREBPs were monotonous as the majority of them, except those of AP2 subfamily, had no intron. An analysis of transcription activities of several closely related and duplicated BdDREB genes showed their functional divergence and redundancy in evolution. The expression of BdAP2/EREBPs in different tissues and the expression of DREB/ERF subfamilies in B. distachyon, wheat and rice under abiotic stresses were investigated by next-generation sequencing and microarray profiling. Our results are valuable for further function analysis of stress tolerant AP2/EREBP genes in B. distachyon. PMID- 26869023 TI - Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer. AB - BACKGROUND: Chemotherapy is the treatment of choice in patients with advanced or metastatic colorectal cancer (CRC) where surgical resection of metastases is not an option. Both irinotecan (IRI) and fluoropyrimidines are often included in first- or second- line chemotherapy treatment regimens in such patients. However, it is not clear whether combining these agents is superior to irinotecan alone. OBJECTIVES: To compare the efficacy and safety of two chemotherapeutic regimens, irinotecan monotherapy or irinotecan in combination with fluoropyrimidines, for patients with advanced CRC when administered in the first or second-line settings. SEARCH METHODS: We searched the following electronic databases to identify randomized controlled trials: Cochrane Colorectal Cancer Group Specialised Register (January 13, 2016), Cochrane Central Register of Controlled Trials (CENTRAL)(The Cochrane Library Issue 12, 2016), Ovid MEDLINE (1950 to January 13, 2016), Ovid EMBASE (1974 to January 13, 2016), registers of controlled trials in progress, references cited in relevant publications and conference proceedings in related fields (BioMed Central and Medscape's Conference). The key authors or investigators of all eligible studies, and professionals in the field were contacted when necessary. The search from January 2016 identified one eligible study, an ongoing trial currently presented as an abstract, to be considered in an update of this review. SELECTION CRITERIA: Randomized controlled trials (RCTs) investigating the efficacy and safety of IRI chemotherapy combined with fluoropyrimidine compared with IRI alone for the treatment of patients with advanced CRC, regardless of treatment line settings. DATA COLLECTION AND ANALYSIS: Study eligibility and methodological quality were assessed independently by the two authors, and any disagreement was solved by a third author. The data collected from the studies were reviewed qualitatively and quantitatively using the Cochrane Collaboration statistical software RevMan 5.3. MAIN RESULTS: Five studies were included in this review with a total of 1,726 patients. The top-up search resulted in an additional ongoing trial, the results of which have not been incorporated in this review. Among five included studies, no reduction in all-cause mortality was observed in the combination arm, with a summary hazard ratio (HR) of 0.91 (95% CI: 0.81-1.02). Longer progression-free survival was observed in those treated with the combination chemotherapy (HR: 0.68, 95% CI: 0.53-0.87), however, this result may have been driven by findings from the single first-line treatment setting study.The quality of evidence for overall survival was low and for progression-free survival was moderate, mainly due to study limitation from the lack of information on randomisation methods and allocation concealment.There were higher risks of toxicity outcomes grade 3 or 4 diarrhoea and grade 1 or 2 alopecia, and a lower risk of grade 3 or 4 neutropenia in controls compared to the invervention group. Evidence for toxicity has been assessed to be low to moderate quality. AUTHORS' CONCLUSIONS: There was no overall survival benefit of the irinotecan and fluoropyrimidine treatment over irinotecan alone, thus both regimens remain reasonable options in treating patients with advanced or metastatic CRC. Given the low and moderate quality of the evidence, future studies with sufficient numbers of patients in each treatment arms are needed to clarify the benefit observed in progression-free survival with combination irinotecan and fluoropyrimidines. PMID- 26869024 TI - Size and zeta-Potential Measurement of Silica Nanoparticles in Serum Using Tunable Resistive Pulse Sensing. AB - The contact of nanoparticles with biological fluids such as serum results in rapid adsorption of proteins at the nanoparticle surface in a layer known as the "protein corona". Protein coatings modify and control the behavior of the nanoparticles potentially altering the aggregation state and cellular response, which may influence their fate and hazard to human health. Cells are likely to interact with the protein interface rather than with bare surface; therefore it is important to study the protein layer and develop appropriate measurement tools. In this study we investigate how adsorbed proteins from serum affect the size and the surface charge of plain and aminated silica nanoparticles. Particle size and size distributions in buffer and serum-based biological media were studied using tunable resistive pulse sensing (TRPS), as well as differential centrifugal sedimentation (DCS) and dynamic light scattering (DLS). Average and single particle zeta-potentials (related to surface charge) were also measured by electrophoretic light scattering (ELS) and TRPS, respectively. Size measurements showed an increase in size of the nanoparticles upon acquisition of a protein layer, thus allowing an estimation of its thickness. DLS proved incapable of providing an accurate measurement of the nanoparticles' size in serum due to the presence of agglomerates. The ability of TRPS to measure sample agglomeration was investigated by comparison with the high resolution technique of DCS. Particle-by particle zeta-potential measurements by TRPS were consistent with those performed with ELS and allowed a description of the zeta-potential distribution within the samples. PMID- 26869025 TI - Differentiation of human gingival mesenchymal stem cells into neuronal lineages in 3D bioconjugated injectable protein hydrogel construct for the management of neuronal disorder. AB - The success of regeneration attempt is based on an ideal combination of stem cells, scaffolding and growth factors. Tissue constructs help to maintain stem cells in a required area for a desired time. There is a need for easily obtainable cells, potentially autologous stem cells and a biologically acceptable scaffold for use in humans in different difficult situations. This study aims to address these issues utilizing a unique combination of stem cells from gingiva and a hydrogel scaffold, based on a natural product for regenerative application. Human gingival mesenchymal stem cells (HGMSCs) were, with due induction, differentiated to neuronal lineages to overcome the problems associated with birth tissue-related stem cells. The differentiation potential of neuronal lineages was confirmed with suitable specific markers. The properties of mesenchymal stem cells in encapsulated form were observed to be similar to free cells. The encapsulated cells (3D) were then subjected to differentiation into neuronal lineages with suitable inducers, and the morphology and gene expression of transient cells were analyzed. HGMSCs was differentiated into neuronal lineages as both free and encapsulated forms without any significant differences. The presence of Nissl bodies and the neurite outgrowth confirm the differentiation. The advantages of this new combination appear to make it a promising tissue construct for translational application. PMID- 26869026 TI - Biophysical evaluation of protein structural flexibility for ligand biorecognition in solid solution. AB - Ligand-protein recognition is increasingly explored through different biophysical approaches, but the effects of protein flexibility are frequently neglected in many applications. The main goal of this contribution is to comparatively study the flexibility and dynamics of homologous model proteins, i.e. human serum albumin/bovine serum albumin (HSA/BSA), in biopolymer-ligand recognition by using computational chemistry based on multispectroscopic data. The results of spectroscopic analyses showed that the recognition of a ligand by a protein formed a noncovalent adduct with a stoichiometry of 1 : 1, and a ligand was situated stably at the subdomain IIA of protein, which corroborates that time resolved fluorescence displaying the autoregulation/transition of protein conformation occurred and this phenomenon has further been proved by circular dichroism. In light of molecular docking and molecular dynamics simulations, we may confirm that the overall stability of proteins strengthens facilely as the recognition ability of homologous proteins for ligands grows larger. Conversely, if the recognition capability is relatively small, the stability of some amino acid residues can also be enhanced, but the stability of integrally homologous proteins (complexed proteins) did not increase significantly. Furthermore, via careful examination of free energy decomposition, we could find that the electrostatic interactions in the HSA-ligand are pronouncedly greater than the BSA-ligand system; however, the van der Waals forces in the BSA-ligand have the most remarkable energy contributions to the protein-ligand reaction. This suggests that the interaction energy of the two biological systems possesses quite notable discrepancies. Probably the results obtained herein would help in revealing the influences of inherent structural features such as flexibility and dynamics of proteins on biomacromolecule-ligand recognition. PMID- 26869027 TI - Sleep-disordered breathing in heart failure. AB - Sleep-disordered breathing-comprising obstructive sleep apnoea (OSA), central sleep apnoea (CSA), or a combination of the two-is found in over half of heart failure (HF) patients and may have harmful effects on cardiac function, with swings in intrathoracic pressure (and therefore preload and afterload), blood pressure, sympathetic activity, and repetitive hypoxaemia. It is associated with reduced health-related quality of life, higher healthcare utilization, and a poor prognosis. Whilst continuous positive airway pressure (CPAP) is the treatment of choice for patients with daytime sleepiness due to OSA, the optimal management of CSA remains uncertain. There is much circumstantial evidence that the treatment of OSA in HF patients with CPAP can improve symptoms, cardiac function, biomarkers of cardiovascular disease, and quality of life, but the quality of evidence for an improvement in mortality is weak. For systolic HF patients with CSA, the CANPAP trial did not demonstrate an overall survival or hospitalization advantage for CPAP. A minute ventilation-targeted positive airway therapy, adaptive servoventilation (ASV), can control CSA and improves several surrogate markers of cardiovascular outcome, but in the recently published SERVE-HF randomized trial, ASV was associated with significantly increased mortality and no improvement in HF hospitalization or quality of life. Further research is needed to clarify the therapeutic rationale for the treatment of CSA in HF. Cardiologists should have a high index of suspicion for sleep-disordered breathing in those with HF, and work closely with sleep physicians to optimize patient management. PMID- 26869028 TI - Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection. AB - Viral infections result in cellular stress responses, which can trigger protein translation shutoff via phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha). Newcastle disease virus (NDV) causes severe disease in poultry and selectively kills human tumour cells. In this report, we determined that infection of HeLa human cervical cancer cells and DF-1 chicken fibroblast cells with NDV maintained protein at early infection times, 0-12 h post-infection (p.i.), and gradually inhibited global protein translation at late infection times, 12-24 h p.i. Mechanistic studies showed that translation inhibition at late infection times was accompanied by phosphorylation of eIF2alpha, a checkpoint of translation initiation. Meanwhile, the eIF2alpha kinase, PKR, was upregulated and activated by phosphorylation and another eIF2alpha kinase, PERK, was phosphorylated and cleaved into two fragments. Pharmacological inhibition experiments revealed that only PKR activity was required for eIF2alpha phosphorylation, suggesting that recognition of viral dsRNA by PKR was responsible for translation shutoff. High levels of phospho-eIF2alpha led to preferential translation of the transcription factor ATF4 and an increase in GADD34 expression. Functionally, GADD34, in conjunction with PP1, dephosphorylated eIF2a and restored protein translation, benefiting virus protein synthesis. However, PP1 was degraded at late infection times, functionally counteracting the upregulation of GADD34. Taken together, our data support that NDV-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2alpha, which is mediated by continual activation of PKR and degradation of PP1. PMID- 26869029 TI - PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7. AB - Tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase that negatively regulates growth factor-induced survival signalling. Here, we demonstrate that PTEN attenuates epidermal growth factor receptor (EGFR) signalling by promoting late endosome maturation by virtue of its protein phosphatase activity. Loss of PTEN impairs the transition of ligand-bound EGFR from early to late endosomes. We unveil Rab7, a critical GTPase for endosome maturation, as a functional PTEN interacting partner. PTEN dephosphorylates Rab7 on two conserved residues S72 and Y183, which are necessary for GDP dissociation inhibitor (GDI)-dependent recruitment of Rab7 on to late endosomes and subsequent maturation. Thus, our findings reveal PTEN-dependent endosome maturation through phosphoregulation of Rab7 as an important route of controlling EGFR signalling. PMID- 26869030 TI - Tensile properties of a split quadriceps graft for ACL reconstruction. AB - PURPOSE: Anatomic double-bundle ACL reconstruction can be performed using different grafts, such as quadriceps tendon. Grafts can be split in either coronal or sagittal planes to approximate the two bundles of the native ACL, but it is unknown whether a difference exists in the graft tensile properties depending on splitting plane. The purpose of this study was to evaluate the tensile properties of split human quadriceps tendon-bone grafts. METHODS: Twenty full-thickness quadriceps tendon-bone grafts were prepared to mimic grafts for double-bundle ACL reconstruction. Ten grafts were split in the sagittal plane, and ten were split in the coronal plane. Each graft underwent cyclic creep testing and load-to-failure testing to compare creep, ultimate load, ultimate elongation, stiffness, and tangent modulus between splitting planes. All parameters were compared between splitting groups (significance p < 0.05). RESULTS: Lateral halves of grafts split in the sagittal plane exhibited a percent creep of 42.5 +/- 12.4 %, ultimate load of 445 +/- 210 N, ultimate elongation of 7.3 +/- 1.9 mm, stiffness of 75.7 +/- 19.9 N/mm, and tangent modulus of 174.0 +/- 99.8 MPa. No differences were found between halves within split tendons or between splitting planes (n.s.). CONCLUSIONS: Overall, splitting quadriceps tendon grafts for anatomic double-bundle ACL reconstruction results in similar tensile properties regardless of splitting plane. Surgeons can split quadriceps tendon in either splitting plane, but should take care to preserve fibres as much as possible. This study provides data that support the use of both coronal and sagittal splits of quadriceps tendons for anatomic double-bundle ACL reconstruction. PMID- 26869031 TI - Knee biomechanics during walking in recurrent lateral patellar dislocation are normalized by 1 year after medial patellofemoral ligament reconstruction. AB - PURPOSE: Gait kinematics and kinetics of the knee before and after medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent lateral patellar dislocation (RPD) are unknown. The purpose of this study was to measure knee kinematics and kinetics during gait before and 1 year after anatomical MPFL reconstruction in patients with RPD and compare the results to healthy individuals. METHODS: Eleven RPD patients were treated using an anatomical MPFL reconstruction procedure. Gait analysis was conducted before and at 3, 6, and 12 months after surgery. For comparison, 15 healthy volunteers with no history of orthopaedic problems in their lower limbs were included as the control group. Knee kinematics and kinetics were analysed during gait. RESULTS: Before surgery, the internal knee extension moment in RPD patients was significantly lower than in controls (P = 0.025). At 3 months post-operatively, there was an additional decrease in knee extension moment compared to before surgery, and so it was still significantly lower than in the control group (P < 0.01). One year post operatively, knee extension moment in the RPD group was significantly increased compared to 3 months post-operatively (P < 0.01). The knee flexion angle in the early stance phase in the RPD group at 3 months post-operatively was significantly lower than that of controls (P < 0.01). Knee kinematics and kinetics were similar to that of controls 1 year after surgery. CONCLUSION: Initially, RPD patients had lower knee extension moments during gait compared with controls, but by 1 year after MPFL reconstruction, knee kinematics and kinetics of gait in the RPD patients had returned to normal. These observations indicate that MPFL reconstruction may help to delay prospective knee OA as long as possible by restoring the conformation of the patellofemoral joint and gait biomechanics by surgery. PMID- 26869033 TI - Computer-assisted navigation decreases the change in the tibial posterior slope angle after closed-wedge high tibial osteotomy. AB - PURPOSE: The purpose of the present study was to compare the change in tibial posterior slope angle (PSA) between patients treated via computer-assisted and conventional closed-wedge high tibial osteotomy (CWHTO). It was hypothesized that a decrease in the PSA would be less in the computer-assisted group than in the conventional group. METHODS: Data on a total of 75 computer-assisted CWHTOs (60 patients) and 75 conventional CWHTOs (49 patients) were retrospectively compared using matched pair analysis. The pre- and postoperative mechanical axis (MA) and the PSA were radiographically evaluated. The parallel angle was defined as the angle between the joint line and the osteotomy surface. The data were compared between the two groups. RESULTS: The postoperative radiographic MA averaged 1.3 degrees +/- 2.6 degrees valgus in the computer-assisted group and 0.3 degrees +/- 3.1 degrees varus in the conventional group. The change in PSA averaged -0.8 degrees +/- 0.9 degrees in the computer-assisted group and -4.0 degrees +/- 2.2 degrees in the conventional group. The parallel angle averaged 0.2 degrees +/- 3.0 degrees in the computer-assisted group and 6.2 degrees +/- 5.3 degrees in the conventional group. CONCLUSION: Computer-assisted CWHTO using four guide pins could avoid inadvertent change in the PSA. The navigation can be used in anticipation of decreasing the risk of change in the PSA in CWHTO, especially in patients whose preoperative PSA is small. The special attention should be paid to locate the hinge axis acutely and to make the parallel proximal and distal osteotomy surfaces during CWHTO. LEVEL OF EVIDENCE: III. PMID- 26869032 TI - Minimally invasive surgical treatment for chronic ankle instability: a systematic review. AB - PURPOSE: The purpose of this study was to determine the evidence-based support for the treatment for chronic ankle instability (CAI) using minimally invasive surgery (MIS) techniques. METHODS: A systematic comprehensive review of the literature was performed on 4 September 2015 using PubMed, EMBASE, Cochrane databases and Web of Science along with the two search concepts: lateral ligament of the ankle (patients) and minimally invasive surgical procedure (intervention). Articles of clinical study on MIS for CAI were included in this review and classified into four MIS categories (arthroscopic repair, non-arthroscopic minimally invasive repair, arthroscopic reconstruction and non-arthroscopic minimally invasive reconstruction) based on the adopted surgical procedure. Included articles were reviewed and assigned a classification according to the research method quality of evidence (Level I-V evidence). Analysis of these studies was then conducted to provide a grade of recommendation for each MIS category. RESULTS: The systematic literature review generated 430 articles, and 33 articles met our inclusion criteria. The highest recommendation was Grade C (poor-quality evidence) to support the use of the arthroscopic repair, arthroscopic reconstruction and non-arthroscopic minimally invasive reconstruction. Insufficient evidence was currently available to make any recommendation (Grade I) for non-arthroscopic minimally invasive repair category. CONCLUSIONS: Despite recent increases in publications on MIS for the treatment for CAI, there was currently poor quality of evidence that was insufficient to allow a high grade of recommendation to support the use of the MIS. This paper should stimulate those surgeons performing higher quality studies in the form of prospective and preferably randomized comparative studies that will be necessary to allow better recommendations for the treatment for CAI with MIS. The present study showed thorough evidence-based recommendation for the clinical use of the MIS based on the comprehensive review of the literature. LEVEL OF EVIDENCE: Systematic review, Level IV. PMID- 26869034 TI - Ischiofemoral impingement: defining the lesser trochanter-ischial space. AB - PURPOSE: The purpose of this study was to define changes in the ischial-lesser trochanteric space associated with medial and lateral hip rotation in neutral and 10 degrees of extension and adduction. METHODS: Twenty-five hip joints from 14 embalmed cadavers (7 males and 7 females) were used for this study. The pelvic region of each cadaver was skeletonized, and the hip capsule released distally. With the hip joint in 0 degrees flexion-extension/abduction-adduction, the distance between the lesser trochanter and ischium was measured in: neutral rotation, 40 degrees medial rotation, and 60 degrees lateral rotation. A one way ANOVA with post hoc analysis determined the difference in the ischiofemoral space in these three positions. An additional position was then tested by laterally rotating the femur with the hip joint positioned in 10 degrees extension and adduction. RESULTS: The average distance between the lesser trochanter and ischium was different (p < .0005) in neutral rotation, 40 degrees medial rotation, and 60 degrees lateral rotation at 2.8 cm (SD 1.1), 4.3 cm (SD 1.2), and 1.4 cm (SD 0.7), respectively. With the hip joint laterally rotated from a starting position of 10 degrees extension and adduction, 21 of 25 (84 %) hips made contact between the lesser trochanter and ischium at an average position of 29 degrees (SD 20) of lateral rotation. CONCLUSIONS: The lesser trochanter is closest to the ischium in lateral rotation and is furthest away in medial rotation when the hip is in neutral flexion-extension/abduction-adduction. The lesser trochanter approximates the ischium when the hip is laterally rotated in 10 degrees extension and adduction. The information gained through this investigation helps to define the pathomechanics associated with ischiofemoral impingement and validate clinical tests to diagnose ischiofemoral impingement. PMID- 26869036 TI - Changes in anteroposterior stability and proprioception after different types of knee arthroplasty. AB - PURPOSE: To compare different types of knee arthroplasty, in selected patients with a knee score above 80 points, for their post-operative changes in anteroposterior (AP) laxity and proprioception. METHODS: Four groups of each ten patients were tested for AP translation after different types of arthroplasty with a KT-1000 device at 30 degrees , 60 degrees and 90 degrees of flexion. Proprioception of the joint was evaluated by joint position sense with three different tests. Clinical outcome of stability and proprioceptive testing was analysed by comparing the results of three (KSS, KOOS and FJS-12) patient reported outcome measurement scores (PROMS) for each of the different implant types. RESULTS: Anteroposterior laxity was observed at 30 degrees and 90 degrees of flexion for the two PS TKA designs included in this study, but not for the UKA or the medial pivot design. All knee designs, except UKA, had an increased laxity at 60 degrees of flexion. Proprioceptive testing was inconclusive. PROMS were not able to identify differences in clinical outcome among different knee designs in these selected patients, despite observed differences in AP laxity. CONCLUSION: Increased AP laxity is a result of the surgical procedure in knee arthroplasty. UKA is the only design mimicking native laxity of the knee. A medial pivot design can obtain the same result as UKA at 30 degrees and 90 degrees of flexion, but not at the importantly cited 60 degrees of flexion as tested under non-load-bearing conditions. The clinical relevance of this study is that despite of an important range of AP translations among the different knee designs, good-to-excellent patient-reported outcome was observed within the findings of this study. LEVEL OF EVIDENCE: II. PMID- 26869035 TI - Diagnostic validity of alternative manual stress radiographic technique detecting subtalar instability with concomitant ankle instability. AB - PURPOSE: To incorporate a diagnostic technique for measuring subtalar motion, namely "talar rotation", into the manual supination-anterior drawer stress radiographs for evaluation of the severity of rotational instability, and to determine its clinical relevance. METHODS: Sixty-six patients with combined injuries of the anterior talofibular (ATFL) and calcaneofibular ligament (CFL) underwent three bilateral manual stress radiographs, and mean increments of anterior talar translation (mm), talar tilt ( degrees ), and talar rotation (%) in the injured ankle compared to the normal opposite side were measured with the technique. Intraobserver and interobserver reliability of each measure was assessed, and the difference in the degree of increments was compared according to the presence of additional cervical ligament insufficiency. RESULTS: Ankle stress radiographic intraobserver and interobserver agreement was ICC = 0.91 and 0.82 for talar rotation (%), ICC = 0.64 and 0.51 for anterior talar translation, and ICC = 0.78 and 0.71 for talar tilt angle, respectively. In group 2 including patients with combined injuries of the ATFL and CFL along with additional cervical ligament insufficiency, a significantly higher increment of talar rotation, mean 6.4% (SD 3.4%), was observed compared to that of talar rotation, mean 4.1% (SD 2.7 ), in the other group (group 1) with an intact cervical ligament (p < 0.001). CONCLUSIONS: A new comprehensive stress radiographic technique for diagnosis of chronic lateral ankle instability presented in this study might be a reliable and representable measurement tool to assess additional injury or instability of the subtalar joint. LEVEL OF EVIDENCE: Prospective cohort study, Level II. PMID- 26869038 TI - In Search of Concomitant Alterations of Dopaminergic and Neurotensinergic Systems in Stress Conditions. AB - The aim of the present article is to review experimental evidence which suggest joint involvement of both the dopaminergic and neurotensinergic systems in stress conditions. At present, the concept of stress refers to an environmental demand exceeding the normal regulatory ability of an organism, particularly during unpredictable and uncontrollable situations. Chronic stress yields devastating effects including cognitive and working memory dysfunctions, for which neurotransmission mediated by the catecholamines dopamine and noradrenaline is crucial. Catecholamine synthesis depends on the rate-limiting enzyme, tyrosine hydroxylase, whose expression is associated with working memory and the response to chronic stress. Neurotensin is a tridecapeptide widely distributed in the nervous system, at both central and peripheral levels, which behaves as a neurotransmitter or neuromodulator. It mediates diverse biological actions including reward, locomotion, pain modulation and stress. Neurotensin and its high affinity NTS1 receptor are densely localized in areas that process emotion (amygdala nucleus), cognition (such as hippocampal nuclei and cortical areas) and the response to stress (hypothalamic nucleus). Experimental evidence indicates a crosstalk between the dopaminergic and the neurotensinergic systems either from an anatomical or a biochemical point of view. It is suggested that a concomitant alteration of dopaminergic and neurotensinergic systems takes place in diverse stress conditions. PMID- 26869037 TI - Autophagy in Neurodegenerative Diseases and Metal Neurotoxicity. AB - Autophagy generally refers to cell catabolic and recycling process in which cytoplasmic components are delivered to lysosomes for degradation. During the last two decades, autophagy research has experienced a recent boom because of a newfound connection between this process and many human diseases. Autophagy plays a significant role in maintaining cellular homeostasis and protects cells from varying insults, including misfolded and aggregated proteins and damaged organelles, which is particularly crucial in neuronal survival. Mounting evidence has implicated autophagic dysfunction in the pathogenesis of several major neurodegenerative disorders, such as Parkinson's disease, Alzheimer's disease and Huntington's disease, where deficient elimination of abnormal and toxic protein aggregates promotes cellular stress, failure and death. In addition, autophagy has also been found to affect neurotoxicity induced by exposure to essential metals, such as manganese, copper, and iron, and other heavy metals, such as cadmium, lead, and methylmercury. This review examines current literature on the role of autophagy in the mechanisms of disease pathogenesis amongst common neurodegenerative disorders and of metal-induced neurotoxicity. PMID- 26869039 TI - Keratan Sulfate Regulates the Switch from Motor Neuron to Oligodendrocyte Generation During Development of the Mouse Spinal Cord. AB - Keratan sulfate (KS) is a sulfated glycosaminoglycan and has been shown to bind to sonic hedgehog (Shh), which act as a morphogen to regulate the embryonic spinal cord development. We found highly sulfated KS was present in the floor plate (including lateral floor plate) and the notochord . This expression colocalized with Shh expression. To understand the roles of KS, we analyzed the embryonic spinal cord of GlcNAc6ST-1, KS chain synthesizing enzyme, knock-out (KO) mice. At E12.5, the pMN domain, whose formation is controlled by Shh signaling, became shifted ventrally in GlcNAc6ST-1 KO mice. In addition, the expression patterns of Patched1 and Gli1, two Shh signaling reporter genes, differed between wild type (WT) and GlcNAc6ST-1 KO mice at E12.5. Next, we focused on cell types generated from the pMN domain; namely, motor neurons and subsequently oligodendrocytes. The number of PDGFRalpha(+) [a marker for oligodendrocyte precursor cells (OPCs)] cells was low in the E12.5 mutant spinal cord, while motor neuron production was increased. Thus the switch from motor neuron generation to OPC generation was delayed in the pMN domain. Furthermore, we investigated the cause for this delayed switch in the pMN domain. The number of Olig2, Nkx2.2 double-positive cells was less in GlcNAc6ST-1 KO mice than in WT mice. In contrast, the number of Olig2, Neurogenin2 (Ngn2) double-positive cells related to the motor neuron specification was significantly greater in the KO mice. These results indicate that KS is important for the late phase Shh signaling and contributes to motor neuron to OPC generation switch. PMID- 26869040 TI - Rutin Inhibits Neuroinflammation and Provides Neuroprotection in an Experimental Rat Model of Subarachnoid Hemorrhage, Possibly Through Suppressing the RAGE-NF kappaB Inflammatory Signaling Pathway. AB - As is known to all, neuroinflammation plays a vital role in early brain injury pathogenesis following subarachnoid hemorrhage (SAH). It has been shown that rutin have a property of inhibiting inflammation in many kinds of animal models. However, the effect of rutin on neuroinflammation after SAH remains uninvestigated. In this study, we investigated the potential effects of rutin on neuroinflammation and the underlying mechanism in an experimental rat model of SAH performed by endovascular perforation. Adult male SD rats were randomly divided into three groups, including sham group, SAH + vehicle group and SAH + rutin group (50 mg/kg) intraperitoneally (i.p.) administered at 30 min after SAH. After sacrificed at 24 h after SAH, all rats were examined by following tests, including neurologic scores, blood-brain barrier permeability, brain water content and neuronal cell death in cerebral cortex. The level of inflammation in brain was estimated by means of multiple molecules, including RAGE, NF-kappaB, and inflammation cytokines. Our results indicated that rutin could significantly downregulate the increased level of REGE, NF-kappaB and inflammatory cytokines in protein level. In addition, rutin could also ameliorate a series of secondary brain injuries such as brain edema, destruction of blood-brain barrier, neurological deficits and neuronal death. This study indicated that rutin administration had a neuroprotective effect in an experimental rat model of SAH, possibly through inhibiting RAGE-NF-kappaB mediated inflammation signaling pathway. PMID- 26869041 TI - Gastrodin Attenuates Cognitive Deficits Induced by 3,3'-Iminodipropionitrile. AB - 3,3'-Iminodipropionitrile (IDPN), one of the nitrile derivatives, can induce persistent neurotoxicity, and therefore cause dyskinesia and cognitive impairments. Gastrodin, a main bioactive ingredient of Gastrodia elata Blume, is shown to greatly improve cognitive function. The aim of this study was to further determine whether administration of gastrodin can ameliorate IDPN-induced cognitive deficits in the Morris water maze (MWM) and novel object recognition (NOR) task, and to explore the underlying mechanisms. Results showed that exposure to IDPN (100 mg/kg/day, for 8 days) significantly impaired spatial and object recognition memory and that repeated treatment with gastrodin (150 mg/kg/day, for 6 weeks) could effectively alleviate the IDPN-induced cognitive impairments as indicated by increased spatial memory and discrimination ratio in the MWM and NOR tests. Gastrodin treatment also reverted IDPN-induced decreases of gamma-aminobutyric acid (GABA) levels and increases of a2 GABAA receptor protein expression in the prefrontal cortex and hippocampus of IDPN-treated rats. These results suggest that gastrodin treatment may provide a novel pharmacological strategy for IDPN-induced cognitive deficits, which was mediated, at least in part, by normalizing the GABAergic system. PMID- 26869042 TI - Neuroprotective Effects of Poly(ADP-ribose)polymerase Inhibitor Olaparib in Transient Cerebral Ischemia. AB - Olaparib was the first poly(ADP-ribose)polymerase inhibitor approved by Food and Drug Administration for oncology treatment. However, its neuroprotective effects have not been elucidated. This study aimed to evaluate the effects of olaparib in transient cerebral ischemia. A mouse model of transient middle cerebral artery occlusion was used. Reperfusion was performed at 2 h after ischemia. Different doses of olaparib (1, 3, 5, 10 and 25 mg/kg) were administered intraperitoneally immediately after reperfusion. Twenty-four hours after ischemia, the neurological score was assessed, and grip and string tests were performed to evaluate the behavioral deficits in the mice. Cresyl violet staining was used to assess cerebral edema and the lesion volume. Immunohistochemistry was performed to evaluate the expression of blood-brain barrier proteins collagen IV and claudin 5, as well as extravasation of IgG. Ischemia induced a neurological deficit, which was significantly ameliorated by olaparib at 3 and 5 mg/kg. However, this neuroprotective effect was not observed in mice treated with either low-dose or high-dose olaparib. Both 3 and 5 mg/kg olaparib markedly reduced cerebral infarction volume, but not cerebral edema. The expression of collagen IV decreased after cerebral ischemia, which was improved by olaparib at 3 and 5 mg/kg. These results were confirmed by the reduction of IgG extravasation with olaparib. Olaparib showed clear neuroprotective effects in transient ischemic mice mainly through the reduction of cerebral infarction and blood-brain barrier damage. PMID- 26869044 TI - [Hypokalemia, a key clinical data for diagnosing primary hyperaldosteronism]. AB - We report a case of a 37 year-old man with a long history of hypertension under treatment, who was admitted at our institution with intense fatigue and weakness of lower limbs. The laboratory results at Emergency Department showed severe hypokalemia. A study of secondary hypertension was carried out. With the initial suspicion of primary hyperaldosteronism, complete blood test was done including plasma renine activity, which was completely suppressed, and plasma aldosterone concentration, which resulted normal. Likewise, an abdomen CT was performed and revealed a left adrenal mass consistent of suprarrenal adenoma. Therefore, a salt loading suppression test was done with subsequent measure of plasmatic renine activity, which was still suppressed, plasma aldosterone concentration, that persisted normal, and a 24-h urinary aldosterone excretion rate, which was clearly high, supporting the suspected diagnosis. After the adrenalectomy, the patient remained asymptomatic with normal blood pressure without treatment and with normal serum potassium levels. PMID- 26869045 TI - Residue level and dissipation pattern of spiromesifen in cabbage and soil from 2 year field study. AB - Spiromesifen is a new class of insecticide used for the control of whiteflies and mites which have developed resistance to the more commonly used neonicotinoids. Dissipation pattern of spiromesifen on cabbage was evaluated over 2 years by conducting supervised field studies as per good agricultural practices. Cabbage and soil samples were extracted and purified using modified QuEChERS method and analyzed through gas chromatography (GC). Confirmatory studies were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The recoveries of spiromesifen from cabbage and soil were between 85.44 and 103.37% with the relative standard deviation (RSD) between 3.2 and 9.4% (n = 6). The limit of detection (LOD) and limit of quantification (LOQ) were 0.003 MUg mL(-1) and 0.01 mg kg(-1), respectively. The measurement uncertainties (MUs) were within 9.9 14.9%. Initial residues of spiromesifen on cabbage were 0.640 and 1.549 mg kg(-1) during 2013 and 0.723 and 1.438 mg kg(-1) during 2014 from treatments at standard and double doses of 125 and 250 g active ingredient (a.i.) ha(-1), respectively. Spiromesifen residue dissipation followed first-order rate kinetics, and it degraded within the half-lives of 2.9 and 3.9 days during 2013 and 3.2 and 4.5 days during 2014. The residue levels reached below the maximum residue limit (MRL; 0.02 mg kg(-1)) within 15-17 days at the standard dose and 24-27 days at the double dose. The field soil analyzed at harvest (30 days) was free from spiromesifen residues. Metabolite spiromesifen-enol was not detected in any sample which was confirmed through LC-MS/MS analysis. PMID- 26869043 TI - Bone marrow-derived mesenchymal stromal cells differ in their attachment to fibronectin-derived peptides from term placenta-derived mesenchymal stromal cells. AB - INTRODUCTION: Human mesenchymal stromal cells (MSCs) can be isolated from different sources including bone marrow and term placenta. These two populations display distinct patterns of proliferation and differentiation in vitro. Since proliferation and differentiation of cells are modulated by cell-matrix interactions, we investigated the attachment of MSCs to a set of peptide-coated surfaces and explored their interactions with peptides in suspension. METHODS: Human MSCs were isolated from bone marrow and term placenta and expanded. Binding of MSCs to peptides was investigated by a cell-attachment spot assay, by blocking experiments and flow cytometry. The integrin expression pattern was explored by a transcript array and corroborated by quantitative reverse transcription polymerase chain reaction and flow cytometry. RESULTS: Expanded placenta-derived MSCs (pMSCs) attached well to surfaces coated with fibronectin-derived peptides P7, P15, and P17, whereas bone marrow-derived MSCs (bmMSCs) attached to P7, but barely to P15 and P17. The binding of bmMSCs and pMSCs to the peptides was mediated by beta1 integrins. In suspension, expanded bmMSCs barely bind to P7, P13, P15, and less to P14 and P17. Ex vivo, bmMSCs failed to bind P7, but displayed a weak interaction with P13, P14, and P15. In suspension, expanded pMSCs displayed binding to many peptides, including P4, P7, P13, P14, P15, and P17. The differences observed in binding of bmMSCs and pMSCs to the peptides were associated with significant differences in expression of integrin alpha2-, alpha4 , and alpha6-chains. CONCLUSIONS: Human bmMSCs and pMSCs show distinct patterns of attachment to defined peptides and maintain differences in expression of integrins in vitro. Interactions of ex vivo bmMSCs with a given peptide yield different staining patterns compared to expanded bmMSCs in suspension. Attachment of expanded MSCs to peptides on surfaces is different from interactions of expanded MSCs with peptides in suspension. Studies designed to investigate the interactions of human MSCs with peptide-augmented scaffolds or peptides in suspension must therefore regard these differences in cell-peptide interactions. PMID- 26869046 TI - Leaching potential of silver from nanosilver-treated textile products. AB - The use of nanosilver as an antibacterial agent for various products has increased, especially so, in textiles. This study aims to investigate the potential of Ag to leach from commercial products which contain nano-Ag by using the toxicity characteristic leaching procedure (TCLP) test in accordance with USEPA method 1311. Eight nano-Ag products were purchased from the market. Only those products that are likely to be disposed of in a landfill after end use were selected. Nano-Ag fabrics of different concentrations were also prepared at the laboratory scale, and the TCLP test was performed on them as well. The current study assumes that the new products were discarded without use. The Ag content was quantified by inductively coupled plasma-mass spectroscopy (ICP-MS) and ranged from 0.95 to 2.82 MUg/g of the product in the commercial products and from 1.49 to 350 MUg/g of the product in the lab-prepared fabrics. In the TCLP test results, Ag concentrations ranged from 4.3 to 64.9 MUg/L in the commercial products and from 28.9 to 28,381 MUg/L in the lab-prepared fabrics. The results also indicate that the amount of Ag released depends on the type of the fabrics. Additionally, the size of the nano-Ag released in percentage is different for each prepared fabric. This study can help in understanding the amount of Ag released during the disposal phase of a product in a landfill. PMID- 26869047 TI - Relationships between trace elements in Posidonia oceanica shoots and in sediment fractions along Latium coasts (northwestern Mediterranean Sea). AB - The Mediterranean endemic seagrass Posidonia oceanica is widely used as a sensitive bioindicator of trace elements (TEs) in the coastal environment. Therefore, a bulk of data exist on TE levels from impacted versus unpolluted sites while only recent studies started comparing TE accumulation in plant compartments versus both water column and sediment characteristics. In this study, six TEs (As, Cd, Cr, Cu, Ni, Pb) were analyzed in P. oceanica shoots related to depth (-10 and -20 m) and to TE concentrations in the different grain size fractions of the sediment, from two Sites of Community interest (SIC) in the central Tyrrhenian Sea. TE concentrations in both shoots and sediment were generally low, except for Cr. Cu was the only element showing significantly different concentrations at the two sites while As differed significantly between samples taken at different depths. TE concentrations in the unsieved sediment were found uncorrelated to TEs in shoots except for the important nutrient Cu (positive correlation). The finest sediment fractions were enriched in TEs and significantly correlated to Cd, Cr, Cu, and Ni concentrations in the shoots. PMID- 26869048 TI - Perchlorate levels found in tap water collected from several cities in Turkey. AB - Perchlorate is an inorganic anion that inhibits iodide transport to the thyroid by sodium-iodide transporters. Because perchlorate is highly soluble, stable, and mobile in water, drinking water is a potential source of perchlorate exposure. When exposed to perchlorate, thyroid dysfunction can be observed in sensitive populations (pregnant woman, infants, and children), especially those with iodide deficiency. The aim of this study was to determine the perchlorate levels in tap water from five cities in Turkey. Perchlorate concentrations of 145 tap water samples collected from Ankara, Isparta, Istanbul, Kayseri, and Sakarya were determined by liquid chromatography-tandem mass spectrometry. Mean and median values were found to be 0.15 and 0.07 MUg/L, respectively. The median values (25 75 % percentile) of Istanbul, Ankara, Sakarya, Isparta, and Kayseri were 0.08 MUg/L (0.04-0.09 MUg/L), 0.07 MUg/L (0.07-0.21 MUg/L), 0.04 MUg/L (0.04-0.04 MUg/L), 0.03 MUg/L (0.02-0.07 MUg/L), and 0.25 MUg/L (0.23-0.31 MUg/L), respectively. The median perchlorate level observed in Kayseri was significantly higher than those found at other cities (p < 0.05). Perchlorate concentrations in water samples were lower than the interim drinking water health advisory level (15 MUg/L) determined by the US Environmental Protection Agency. This study showed that perchlorate in drinking water is not the main source of exposure in these cities. Future studies should be performed to determine perchlorate levels in other potential sources, such as food products. PMID- 26869050 TI - Neoadjuvant nab-paclitaxel in breast cancer: trial results and patient care. PMID- 26869049 TI - Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. AB - BACKGROUND: In metastatic breast cancer, nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel. The GeparSepto (GBG 69) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment. METHOD: In a phase 3 randomised trial, we enrolled patients with previously untreated unilateral or bilateral primary invasive breast cancer and randomly assigned them in a 1:1 ratio using dynamic allocation and Pocock minimisation by breast cancer subtype, Ki67 and SPARC expression. Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2) (after study amendment, 125 mg/m(2)) on days 1, 8, and 15 for four 3-week cycles, or solvent-based intravenous paclitaxel 80 mg/m(2) on days 1, 8, and 15 for four 3-week cycles. Taxane treatment was followed in both groups by intravenous epirubicin 90 mg/m(2) plus intravenous cyclophosphamide 600 mg/m(2) on day 1 for four 3-week cycles. Patients with HER2 positive tumours received concurrent trastuzumab 6 mg/kg (loading dose 8 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) on day 1 of every 3-week cycle. Trastuzumab and pertuzumab were given every 3 weeks concomitantly with chemotherapy for all cycles. This report is the final analysis of the primary endpoint, pathological complete response (ypT0 ypN0), analysed for all patients who started treatment (modified intention to treat). We used a closed test procedure to test for non-inferiority, with the nab-paclitaxel group calculated as non-inferior to the solvent-based paclitaxel group if the lower 95% CI for the OR was above 0.858 (OR equivalent to pathological complete response [33%] minus a 10% non-inferiority margin [3.3%]; 29.7%). We planned to test for superiority only in case of a positive non-inferiority test, using an alpha of 0.05. Safety was assessed in all patients who received study drug. The trial is registered with ClinicalTrials.gov, number NCT01583426. FINDINGS: Between July 30, 2012, and Dec 23, 2013, we randomly assigned 1229 women, of whom 1206 started treatment (606 with nab-paclitaxel and 600 with solvent-based paclitaxel). The nab paclitaxel dose was reduced after enrolment of 464 participants to 125 mg/m(2) due to increased treatment discontinuation and sensory neuropathy in this group. Pathological complete response occurred more frequently in the nab-paclitaxel group (233 [38%, 95% CI 35-42] patients) than in the solvent-based paclitaxel group (174 [29%, 25-33] patients; OR 1.53, 95% CI 1.20-1.95; unadjusted p=0.00065). The incidence of grade 3-4 anaemia (13 [2%] of 605 patients in the nab-paclitaxel group vs four [1%] of patients in the solvent-based paclitaxel group; p=0.048) and peripheral sensory neuropathy grade 3-4 (63 [10%] patients receiving any nab-paclitaxel dose; 31 [8%] of patients starting with 125 mg/m(2) and 32 [15%] of patients starting with 150 mg/m(2); vs 16 [3%] in the solvent based paclitaxel group, p<0.001) was significantly higher for nab-paclitaxel than for solvent-based paclitaxel. Overall, 283 (23%) patients were noted to have at least one serious adverse event (based on study drug received), 156 (26%) in the nab-paclitaxel group and 127 (21%) in the solvent-based paclitaxel group (p=0.057). There were three deaths (during epirubicin plus cyclophosphamide treatment) in the nab-paclitaxel group (due to sepsis, diarrhoea, and accident unrelated to the trial) versus one in the solvent-based paclitaxel group (during paclitaxel treatment; cardiac failure). INTERPRETATION: Substituting solvent based paclitaxel with nab-paclitaxel significantly increases the proportion of patients achieving a pathological complete response rate after anthracycline based chemotherapy. These results might lead to an exchange of the preferred taxane, solvent-based paclitaxel, for nab-paclitaxel in therapy for primary breast cancer. FUNDING: Celgene, Roche. PMID- 26869051 TI - Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model. AB - Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individual-level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26869052 TI - Non alcoholic fatty liver disease increases the mortality from acute coronary syndrome: an observational study from Sri Lanka. AB - BACKGROUND: Non alcoholic fatty liver disease is an independent risk factor for coronary artery disease. But its effect on acute coronary syndrome is not clear. We performed this study to identify the prevalence of NAFLD in patients with ACS admitted to a tertiary care center in Sri Lanka. We also described the association of NAFLD with the severity of ACS predicted by the GRACE score. METHODS: We performed a descriptive study including all consecutive patients with non-fatal ACS admitted to Colombo South Teaching Hospital from 01/02/2014 to 30/04/2014. Patients with excessive alcohol consumption, established cirrhosis and patients with identified risk factors for liver disease were excluded from the study. All patients underwent ultrasound scan of liver. RESULTS: There were 120 participants, 75 (62.5%) males and 45 (37.5%) females with acute coronary syndrome. Average age was 61.28 +/- 11.83 years. NAFLD was seen in 56 (46.7%) patients with ACS. Patients with NAFLD had a higher GRACE score than patients without NAFLD (120.2 +/- 26.9 Vs 92.3 +/- 24.2, p < 0.001). Increased age and presence of NAFLD conferred a higher mortality risk from ACS as predicted by GRACE score. Patients with NAFLD had a higher predicted mortality during in-ward stay (adjusted OR 31.3, CI 2.2-439.8, p = 0.011) and at 6 months after discharge (adjusted OR 15.59, CI 1.6-130.6, p = 0.011). CONCLUSIONS: Patients with NAFLD have a higher predicted mortality from acute coronary syndrome and thus require aggressive treatment of CAD. It is important to consider this novel risk factor when risk stratifying patients with ACS. PMID- 26869053 TI - Spontaneous regression and complete disappearance of the vein of Galen aneurysmal malformation. AB - INTRODUCTION: Thrombosis is frequently observed in Galen malformation, but propagation of thrombosis resulting in the disappearance of the aneurysmal malformation is a very rare clinical condition. CASE REPORT: A rare case of spontaneous regression and disappearance of the vein of Galen aneurysmal malformation (VoGAM) in a pediatric patient with repeated generalized seizure, increased head circumference, and congestive heart failure is recorded. The course of regression from infancy to 8 years of age has been depicted. Radiological studies initially demonstrated VoGAM complicated by an intra cerebral hemorrhage and hydrocephalus, which later underwent spontaneous regression. Long-term clinical and radiological follow-up is presented. DISCUSSION: Different conditions including hemodynamic alteration, compression of adjacent hematoma, and narrowing of related vascular structures have been described to cause thrombosis of VoGAM. The relevant literature to address possible mechanism is reviewed. PMID- 26869054 TI - Comparison of heart rate changes with ictal tachycardia seizures in adults and children. AB - PURPOSE: Lower heart rate variability (HRV) is known to make patients more susceptible to tachycardia and possibly sudden unexpected death in epilepsy (SUDEP). The heart rate (HR) at which tachycardia is present may vary by age. To date, no study has been done comparing adult and child seizures at different time points. The purpose of this study was to compare the frequency of HR changes with ictal tachycardia (IT) seizures at different time points in adults versus children. METHODS: We retrospectively assessed the changes in the HR of 99 IT seizures in children and 96 IT seizures in adults. The difference between adults and children in gender, hemispheric lateralization or sleep/wakefulness, or seizure type on the HR changes and the difference between children and adults during 10 s preictal, ictal onset, and ictal and 60 s postictal were separately assessed. RESULTS: The HR difference and maximum HR increase with aging in children. The seizure duration in adults lasted longer as compared with that in children. There are higher HR at different points and HR difference at 10 s preictal as compared to baseline in children. CONCLUSIONS: The study illustrates that age and duration were respectively related to HR differences distinguishing children from adults. There may be an age-related effect of HR changes associated with seizures, with higher HR at different times and HR difference at 10 s before seizure onset as compared to baseline in children, which might explain that children are more likely to predict epileptic seizures than adults, contributing to subclinical seizures and treatment efficiency in refractory patients. PMID- 26869055 TI - Iatrogenic intradiploic cerebrospinal fluid collection. AB - BACKGROUND: Cases of intradiploic cerebrospinal fluid (CSF) collections have been previously reported in the literature with various underlying causes. We focus specifically on the iatrogenic cases of this rare but possible neurosurgical complication discussing the possible pathophysiological mechanisms and management strategy. CASE DESCRIPTION: A 14-year-old boy was admitted in our institute with recurrent headache and worsening attention deficits. He was previously treated twice for a Chiari malformation type I. The performed imaging showed the persisting lower position of the cerebellar tonsils with a syrinx within the cervical spinal cord and a fluid collection within the occipital bone with thinning of outer and inner table. Occipital bone decompression with resection of the intradiploic cavity and enlarging duraplasty was performed. Postoperative imaging confirmed the removal of the iatrogenic-induced focal bone alteration. DISCUSSION AND CONCLUSION: Iatrogenic intradiploic focal fluid accumulation can occur when a dural defect combines with an inner table defect of the calvaria or vertebral bones. Though rare, such a complication should be taken into account when postoperative imaging suggests a focal fluid collection inside the theca. The surgical excision of the lesion is mandatory due to the natural history of progression. PMID- 26869056 TI - Mapping of the biomedical literature evaluation competencies based on pharmacy students' feedback. AB - BACKGROUND: This study aims to map the learned curriculum based on students' feedback regarding the biomedical literature evaluation competencies in a pharmacy curriculum, to evaluate teaching methods and to report students' longitudinal self-assessment of their achievement of related learning outcomes as they progress from didactic to experiential courses. METHODS: The biomedical literature evaluation competencies were mapped in three courses delivered during different pharmacy professional years (PPY): Drug Information and Literature Evaluation (PHA421) offered in the second PPY, Pharmacoeconomics (PHA557) and Professional Pharmacy Practice Experience-Hospital/Drug Information Services (PHA570) offered in the third PPY. A unified survey was developed to collect information from students at the beginning and completion of these courses. Survey results were then compared to school assessment data of identified courses for triangulation of findings. RESULTS: Listed student learning outcomes are consistently achieved through all three courses with more assertion from the students at the completion of the applied experiential course PHA 570 (>90 % agree or strongly agree). In terms of delivery methods, 84 % of students perceived the benefits of active learning methods in reinforcing acquired skills and increasing confidence in knowledge and critical thinking in a less stressful learning environment. Results shown at the end of each course indicate a favorable student response from one course to the next where almost all students replied with 'agree to strongly agree' to survey questions assessing their readiness to critically evaluating trials (72 %, 96 % and 92 %) in PHA421, PHA557 and PHA570, respectively. Study findings are in congruence with school assessment database of the selected courses. CONCLUSION: Formative assessment results demonstrated acquisition of required analytical skills, and completion of course learning outcomes as students progressed from introductory to advanced courses covering the biomedical literature component. PMID- 26869057 TI - The time course of visuo-spatial working memory updating revealed by a retro cuing paradigm. AB - We investigated the influence of non-cued working memory representations on further information processing. A retro-cue indicated if items on the left or right side of a previous memory array remained relevant. Subsequently, a central probe item was presented with a varying stimulus onset asynchrony (SOA: 300, 400, 600, 1,000, 1,800 ms). Participants had to state whether this stimulus was shown on the cued side of the memory array. The probe was either a cued, non-cued or new item. Non-cued probes were associated with delayed response times and an increased frontal negativity from 400-600 ms indicating a higher processing conflict compared to new probes. These effects were strongest for the 300 and 400 ms SOAs and decreased in longer SOA conditions, pointing toward a benefit when there was sufficient time for working memory updating. Furthermore, contralateral negativities at posterior (PCN) and anterior sites (ADAN) reflected the attentional orienting toward cued information while selective retention was associated with a sustained suppression of posterior induced alpha power contralateral to retro-cue direction. Results suggest that retro-cue induced updating of visuo-spatial working memory requires about 500 ms to transfer the non-cued contents into a passive and fragile short-term memory state with less impact on ongoing information processing. PMID- 26869059 TI - Does Hemophilia Increase the Risk of Postoperative Blood Transfusion After Lower Extremity Total Joint Arthroplasty? AB - BACKGROUND: Hemophilia can lead to the development of arthropathies secondary to recurrent hemarthroses. However, given these patients' bleeding tendencies, postoperative complications associated with blood loss are a considerable concern. METHODS: We identified men in the Nationwide Inpatient Sample who underwent total hip or knee arthroplasty between January 1998 and December 2010. We used propensity scores to match 332 hemophiliacs (267 hemophilia A, 65 hemophilia B) to a comparison cohort of 996 patients in a 1:3 ratio, according to the site of arthroplasty, year of admission, age, race, and Charlson and Deyo score. RESULTS: The incidence of any postoperative transfusion was 15.06% for hemophiliacs, compared with 9.84% for the matched comparison cohort (P = .012). For hemophiliacs, the odds ratio was 1.60 (95% confidence interval [CI] = 1.11 2.31; P = .013) for any transfusion, 1.90 (95% CI = 1.24-2.92; P = .003) for allogenic transfusion, and 1.05 (95% CI = 0.56-1.95; P = .888) for autogenic transfusion. CONCLUSION: Hemophilia is associated with an increased risk of blood transfusion after lower extremity total joint arthroplasty. Patients and providers should discuss these risks before surgery, and insurers should consider incorporating this comorbidity into bundled payments for total hip and knee arthroplasty. PMID- 26869060 TI - Perioperative Predictors of Length of Stay After Total Hip Arthroplasty. AB - BACKGROUND: Few studies had examined whether specific patient variables or performance on functional testing can predict length of stay (LOS) after total hip arthroplasty (THA). Such tools would enable providers to minimize prolonged LOS by planning appropriate discharge dispositions preoperatively. METHODS: We prospectively recruited 120 patients undergoing a THA through an anterior (n = 40), posterior (n = 40), or lateral (n = 40) approach. Patients performed a timed up-and-go (TUG) test preoperatively to determine if it was predictive of hospital LOS after THA. Other variables of interest included patient age, body mass index, age-adjusted Charlson Comorbidity Index, mean procedure time, and time spent in the postanesthetic care unit. A logistic regression analysis was performed to determine which variables predicted LOS greater than 48 hours, which is our institution's target time to discharge. RESULTS: The TUG test was predictive of LOS beyond 48 hours. For every 5-second interval increase in TUG time, patients were twice as likely to stay in hospital beyond 48 hours (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.02-4.01, P = .043). Patient age (OR = 0.97, 95% CI = 0.90-1.05, P = .46), body mass index (OR = 1.01, 95% CI = 0.86-1.18, P = .90), Charlson Comorbidity Index (OR = 1.29, 95% CI = 0.68-2.44, P = .44), mean procedure time (OR = 1.05, 95% CI = 0.97-1.14, P = .27), and mean time in the postanesthetic care unit (OR = 1.00, 95% CI = 0.99-1.00, P = .94) were not predictive of increased LOS. CONCLUSION: The TUG test was predictive of hospital LOS after THA. It is a simple functional test that can be used to assist with discharge planning preoperatively to minimize extended hospital stays. PMID- 26869058 TI - Compliance with Sport Injury Prevention Interventions in Randomised Controlled Trials: A Systematic Review. AB - INTRODUCTION: Sport injury prevention studies vary in the way compliance with an intervention is defined, measured and adjusted for. OBJECTIVE: The objective of this systematic review was to assess the extent to which sport injury prevention randomised controlled trials (RCTs) have defined, measured and adjusted results for compliance with an injury prevention intervention. METHODS: An electronic search was performed in MEDLINE, PubMed, the Cochrane Center of Controlled Trials, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PEDro (Physiotherapy Evidence Database) and SPORTDiscus. English RCTs, quasi-RCTs and cluster-RCTs were considered eligible. Trials that involved physically active individuals or examined the effects of an intervention aimed at the prevention of sport- or physical activity-related injuries were included. RESULTS: Of the total of 100 studies included, 71.6 % mentioned compliance or a related term, 68.8 % provided details on compliance measurement and 51.4 % provided compliance data. Only 19.3 % analysed the effect of compliance rates on study outcomes. While studies used heterogeneous methods, pooled effects could not be presented. CONCLUSIONS: Studies that account for compliance demonstrated that compliance significant affects study outcomes. The way compliance is dealt with in preventions studies is subject to a large degree of heterogeneity. Valid and reliable tools to measure and report compliance are needed and should be matched to a uniform definition of compliance. PMID- 26869061 TI - Vascular Complications After Total Knee Arthroplasty-A Single Institutional Experience. AB - BACKGROUND: Vascular complications during total knee arthroplasty (TKA) are uncommon but potentially devastating. We evaluated cases of vascular complication during TKA in our high-volume, community hospital system. METHODS: Patients were identified by cross-referencing billing codes for TKA with diagnosis codes for vascular complication during the same hospital stay between January 1, 2010 and December 31, 2014. Clinical and radiographic data, time to diagnosis, intervention, and outcomes were collected. RESULTS: We identified 13 vascular complications in 9951 TKAs (0.13%). Average age was 66.2 years (95% CI: 5.55; range: 54.1-87.9), 12 (92.3%) were female, average body mass index was 32.3 (5.17; 20-50), and average Charlson Comorbidity Index was 4.08 (1.03; 2-7). Black females (relative risk = 18.33, 95% CI: 6.20-54.22) were at particularly high risk. Preoperatively, 6 knees exhibited varus coronal malalignment and 2 valgus malalignment (only 1 >15 degrees ). None had flexion contracture >10 degrees . Four knees exhibited vascular calcifications on preoperative radiographs. Twelve were diagnosed and treated the same day as index TKA and 1 on postoperative day 2. All underwent interventions: 9 stents, 2 endarterectomies, 1 thrombectomy, and 1 bypass. One patient sustained a peroneal nerve injury; 3 had persistent stiffness postoperatively that improved after manipulation. There were no revision surgeries, further vascular intervention, compartment syndrome, periprosthetic joint infection, amputation, or mortality. CONCLUSION: Incidence of vascular complications at our community-based hospital system is in line with previous reports. Black race and female gender were significant risk factors. Although outcomes were remarkable for a high rate of stiffness and one peroneal neuropathy, the devastating complications of amputation, compartment syndrome, periprosthetic joint infection, or early mortality were not observed. PMID- 26869062 TI - Reduction Osteotomy vs Pie-Crust Technique as Possible Alternatives for Medial Release in Total Knee Arthroplasty and Compared in a Prospective Randomized Controlled Trial. AB - BACKGROUND: To compare the gap change between the pie-crust technique and reduction osteotomy to determine their effects on flexion and extension gaps and their success rates in achieving ligament balancing during total knee arthroplasty. METHODS: In a prospective randomized controlled trial, 106 total knee arthroplasties were allocated to each group with 53 cases. If there was a narrow medial gap with an imbalance of >=3 mm after the initial limited medial release, either reduction osteotomy or pie-crust technique was performed. The changes of extension and flexion medial gaps along with the success rate of mediolateral balancing were compared. RESULTS: There was a significant difference in the change of medial gap in knee extension with mean changes of 3.5 +/- 0.5 mm and 2.3 +/- 0.8 mm in the reduction osteotomy and pie-crust groups, respectively (P < .001). For flexion gap, greater change was found in the pie-crust group compared with the reduction osteotomy group; the mean medial gap changes in knee flexion were 1.1 +/- 0.5 mm and 2.3 +/- 1.2 mm in the reduction osteotomy and pie crust groups, respectively. The success rates were 90.6% and 67.9% in reduction osteotomy and pie-crust groups, respectively (P = .007). CONCLUSION: As an alternative medial release method, reduction osteotomy was more effective in extension gap balancing, and pie-crust technique was more effective in flexion gap balancing. The overall success rate of mediolateral ligament balancing was higher in the reduction osteotomy group than in the pie-crust group. PMID- 26869063 TI - No Increased Risk of Knee Arthroplasty Failure in Patients With Positive Skin Patch Testing for Metal Hypersensitivity: A Matched Cohort Study. AB - BACKGROUND: It is unclear whether a positive skin patch test for metal allergy in patients with skin hypersensitivity to metals is associated with an increased risk of total knee arthroplasty (TKA) failure. Our aim was to determine whether patients with a history of metal allergy who had a positive skin patch test (SPT+) had worse outcomes after primary TKA compared with those with a negative skin patch test and compared with controls. METHODS: Over 12 years, 127 patients underwent 161 TKA after skin patch testing (SPT; 56 were positive). Cases were matched by age, gender, body mass index, American Society of Anesthesiologists score, implant type, and implant manufacturer to 161 control knee arthroplasties without any prior history of metal allergy and no SPT. Median follow-up was 5.3 years. Differences in outcome measures were assessed between groups. RESULTS: Patients with a SPT+ to metal did not have a higher complication, reoperation, or revision rates compared with patients with a SPT- and matched controls. Survivorship free of revision at 5 years was 98.1% for SPT+; 100% for SPT-; 97.6% for SPT+ controls, 99.0% for SPT- controls. There was no statistically significant difference in postoperative pain between SPT+ and SPT- patients and matched controls. CONCLUSION: This study was designed to evaluate the effect of metal hypersensitivity on TKA outcomes and the role of SPT in patients before TKA. In this study, a SPT+ for metals was of little practical value in predicting the midterm outcome after TKA and cannot be strongly recommended as a method to guide the selection of implant type. PMID- 26869064 TI - Topical Tranexamic Acid May Improve Early Functional Outcomes of Primary Total Knee Arthroplasty. AB - INTRODUCTION: The use of tranexamic acid (TXA) reduces postoperative anemia and blood transfusion requirements. We investigated if these beneficial effects improve the early outcomes of primary total knee arthroplasty (TKA). METHODS: We retrospectively studied 166 consecutive patients (179 TKAs) who received topical TXA (3 g before tourniquet deflation). This "study group" was compared with a "control group" of 197 consecutive patients (209 TKAs) in whom no TXA was used. We captured outcomes during the first 4 postoperative months. Knee Society score (KSS) was determined preoperatively, 6 weeks, and 4 months postoperatively. The outcomes were compared using univariate analysis. Multiple logistic regressions were calculated to assess differences between groups in KSS at 6 weeks and 4 months, controlling for age, sex, body mass index, and preoperative KSS. RESULTS: Postoperative hemoglobin was significantly higher in the study than that in the control group on day 1, day 2, and at discharge (P < .0001). Blood transfusions were required in 5% and 22% of patients (P < .001), respectively. Six weeks postoperatively, the functional KSS and its 5 categories (ability to walk, negotiate stairs up and down, stand up from a chair, and the use of support) were significantly higher in the study than those in the control group (P <= .001). Four months postoperatively, there was no difference in the KSS between the groups. DISCUSSION: Our study suggests that the clinical benefit of topical TXA administration extends beyond the hospitalization period. Its use may improve knee function during the first 6 postoperative weeks. This beneficial clinical effect seems to be negligible afterward. PMID- 26869065 TI - Surgical Site Infection After Total Knee Arthroplasty: Risk Factors in Patients With Timely Administration of Systemic Prophylactic Antibiotics. AB - BACKGROUND: Surgical site infection (SSI) after total knee arthroplasty (TKA) is a catastrophic complication. Administration of prophylactic antibiotics within 60 minutes before surgery is a well-established strategy to prevent SSI. The study is aimed to identify the risk factors for SSI regarding primary TKA in patients with timely administration of systemic prophylactic antibiotics. METHODS: A retrospective review of patients with primary TKA between 2009 and 2013 was conducted. Patients who had prophylactic antibiotics administered after skin incision or >60 minutes before skin incision were excluded. RESULTS: Of the 3152 patients enrolled, the incidence of SSI and deep-implant SSI was 1.52% and 0.79%, respectively. Charlson Comorbidity Index >=3 was an independent risk factor for both SSI (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.24-4.44, P = .01) and deep-implant SSI (OR, 3.46; 95% CI, 1.52-7.91, P < .01). Optimal dose of systemic antibiotics adjusted by patients' body weight for prophylaxis (OR, 0.29; 95% CI, 0.17-0.62, P < .01) and using antibiotic-laden bone cement (OR, 0.33; 95% CI, 0.17-0.64, P < .01) were significant protective factors for SSI. Meanwhile, using antibiotic-laden bone cement (OR, 0.31; 95% CI, 0.13-0.76, P = .01) also significantly decreased the risk of deep-implant SSI. CONCLUSION: Our findings highlight the importance of appropriate dosage of prophylactic antibiotics and use of antibiotic-laden cement in preventing SSI after primary TKA. For prevention of deep-implant SSI, using antibiotic-laden bone cement seems to be an advisable strategy. PMID- 26869066 TI - Perioperative Dexamethasone Administration Does Not Increase the Incidence of Postoperative Infection in Total Hip and Knee Arthroplasty: A Retrospective Analysis. AB - BACKGROUND: Dexamethasone is frequently used for the treatment of postoperative nausea and vomiting and as an adjunct in multimodal postoperative analgesia after total joint arthroplasty; however, the incidence of periprosthetic joint infection (PJI) after the use of perioperative dexamethasone in total joint arthroplasty has yet to be fully elucidated. METHODS: A retrospective chart review was conducted of all patients who underwent total hip or knee arthroplasty (N = 6294) between January 1, 2002 and January 31, 2014. The primary outcome was PJI requiring surgical intervention. Patients were subdivided into 2 cohorts; patients who received perioperative dexamethasone, a single 4- to 10-mg intravenous dose, as prophylaxis against postoperative nausea and vomiting (Dex group; N = 557) and those that did not receive perioperative dexamethasone (No Dex group; N = 5737). Secondary measures included timing of infection, culture data, and the type and number of subsequent procedures. Statistical analysis was performed using a chi-square or Fisher's exact test where appropriate. RESULTS: Seventy-four joints of the 6294 joints included in this analysis ultimately developed a PJI for an overall incidence of infection of 1.2%. Seven of the 557 joints (1.3%) in the Dex group developed a PJI; 67 of the 5737 joints (1.2%) in the No Dex group developed an infection. This difference was not significant (P = .8022). No significant difference in the timing of infection or the number of subsequent procedures was seen. CONCLUSION: A single intravenous perioperative dose of dexamethasone had no statistically significant difference in the rate of PJI after total hip or knee arthroplasty. PMID- 26869067 TI - Burden of stroke attributable to selected lifestyle risk factors in rural South Africa. AB - BACKGROUND: Rural South Africa (SA) is undergoing a rapid health transition characterized by increases in non-communicable diseases; stroke in particular. Knowledge of the relative contribution of modifiable risk factors on disease occurrence is needed for public health prevention efforts and community-oriented health promotion. Our aim was to estimate the burden of stroke in rural SA that is attributable to high blood pressure, excess weight and high blood glucose using World Health Organization's comparative risk assessment (CRA) framework. METHODS: We estimated current exposure distributions of the risk factors in rural SA using 2010 data from the Agincourt health and demographic surveillance system (HDSS). Relative risks of stroke per unit of exposure were obtained from the Global Burden of Disease Study 2010. We used data from the Agincourt HDSS to estimate age-, sex-, and stroke specific deaths and disability adjusted life years (DALYs). We estimated the proportion of the years of life lost (YLL) and DALY loss attributable to the risk factors and incorporate uncertainty intervals into these estimates. RESULTS: Overall, 38 % of the documented stroke burden was due to high blood pressure (12 % males; 26 % females). This translated to 520 YLL per year (95 % CI: 325-678) and 540 DALYs (CI: 343-717). Excess Body Mass Index (BMI) was calculated as responsible for 20 % of the stroke burden (3.5 % males; 16 % females). This translated to 260 YLLs (CI: 199-330) and 277 DALYs (CI: 211 350). Burden was disproportionately higher in young females when BMI was assessed. CONCLUSIONS: High blood pressure and excess weight, which both have effective interventions, are responsible for a significant proportion of the stroke burden in rural SA; the burden varies across age and sex sub-groups. The most effective way forward to reduce the stroke burden requires both population wide policies that have an impact across the age spectra and targeted (health promotion/disease prevention) interventions on women and young people. PMID- 26869069 TI - Early assessment of a rapid alternative method for the estimation of the biomethane potential of sewage sludge. AB - This short communication briefly presents a rapid method using a fluorescent redox indicator, similar to resazurin, in order to estimate the biodegradability of sewage sludge during anaerobic digestion (AD). The biodegradability and by extension the Biochemical Methane Potential (BMP) of nineteen municipal sludge samples (primary, biological and tertiary) were investigated and estimated in only 48 h. Results showed the relevance to follow the metabolic activity of anaerobic sludge by the kinetic of probe reduction. The extended lag phase of inoculum indicated an impact of pre-treatments on enzyme activity. The comparison with Automatic Methane Potential Test System II (AMPTS) confirmed the estimated values of BMP according to an uncertainty limit of 25%. These first results highlight the interest of this rapid assay as a preliminary tool of the biodegradability of sewage sludge in anaerobic digestion. PMID- 26869070 TI - Microbiological methods for surveillance of carrier status of multiresistant bacteria. AB - The presence of colonised patients is one of the main routes for the spread of multiresistant bacteria, and its containment is a clinical and public health priority. Surveillance studies are essential for early detection of colonisation by these bacteria. This article discusses the different microbiological methods, both based on culturing and molecular methods, for detection of carriers of multiresistant bacteria. Those species with a high clinical/epidemiological impact or generating therapeutic difficulties are included: Methicillin-resistant Staphylococcus aureus, Enterococcus spp. resistant to glycopeptides, enterobacteriaceae producing extended spectrum beta-lactamases and plasmid mediated AmpC, carbapenemases producing enterobacteriaceae, Acinetobacter baumannii and multiresistant Pseudomonas aeruginosa. The information in this document should be considered as a structure matrix to be tailored to the specific needs of each centre. PMID- 26869068 TI - Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD. AB - Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD. PMID- 26869071 TI - Characterisation of carbapenem-resistance mechanisms in clinical Pseudomonas aeruginosa isolates recovered in a Spanish hospital. AB - INTRODUCTION: Carbapenems are the beta-lactam antibiotics with the best spectrum of activity in the treatment of Pseudomonas aeruginosa infections. The objective of this study was to molecularly characterise a collection of carbapenem resistant P. aeruginosa isolates (PARC). METHODS: A total of 85 PARC isolates were recovered from 60patients in the Hospital San Pedro, Logrono (period 2008 2011). Clonal relationship was determined using pulsed-field gel electrophoresis (PFGE), susceptibility testing to 15anti-pseudomonal agents was performed using the disk diffusion method, and alterations in oprD, characterisation of integrons and molecular typing (MLST) using PCR and sequencing. RESULTS: The 85 PARC were classified into 35 different PFGE profiles. Of the 61selected strains from 60patients all of them were multiresistant, although none of them showed a carbapenemase phenotype. High polymorphism was detected in OprD, emphasising that 59% of the strains had a premature stop codon. ISPa1328 and ISPsp4 insertion sequences truncated oprD gene into 2 strains (GenBank KF517097 and KF517098). Two thirds (67%) of the strains showed class 1 integrons with genes encoding aminoglycoside modifying enzymes, and 2 of them carried a new integron: aac(3) Ia+aadA1h, named In272, GenBank GQ144317. Four sequence types were detected (Strain Nos.): ST175 (35), ST308 (3), ST235 (2), and ST639 (1). CONCLUSION: Multidrug resistance, high polymorphism in oprD, a high percentage of integrons, moderate clonal relationship of strains, and the high epidemic dissemination of high-risk clones are clinical aspects of great concern in order to eradicate the spread of PARC. PMID- 26869072 TI - Genetic diversity at the Dhn3 locus in Turkish Hordeum spontaneum populations with comparative structural analyses. AB - We analysed Hordeum spontaneum accessions from 21 different locations to understand the genetic diversity of HsDhn3 alleles and effects of single base mutations on the intrinsically disordered structure of the resulting polypeptide (HsDHN3). HsDHN3 was found to be YSK2-type with a low-frequency 6-aa deletion in the beginning of Exon 1. There is relatively high diversity in the intron region of HsDhn3 compared to the two exon regions. We have found subtle differences in K segments led to changes in amino acids chemical properties. Predictions for protein interaction profiles suggest the presence of a protein-binding site in HsDHN3 that coincides with the K1 segment. Comparison of DHN3 to closely related cereals showed that all of them contain a nuclear localization signal sequence flanking to the K1 segment and a novel conserved region located between the S and K1 segments [E(D/T)DGMGGR]. We found that H. vulgare, H. spontaneum, and Triticum urartu DHN3s have a greater number of phosphorylation sites for protein kinase C than other cereal species, which may be related to stress adaptation. Our results show that the nature and extent of mutations in the conserved segments of K1 and K2 are likely to be key factors in protection of cells. PMID- 26869073 TI - Bone Mineral Density, 25-OH Vitamin D and Inflammation in Patients with Psoriasis. AB - BACKGROUND/PURPOSE: Low levels of vitamin D may play a role in the pathogenesis of psoriasis and is related to increased risk of osteoporosis. There are a few studies showing increased rate of osteoporosis in patients with psoriasis; however, none of them investigated impact of vitamin D levels and gender status together. We aimed to evaluate relationship between vitamin D and osteoporosis in psoriasis patients with an emphasis on gender difference. METHODS: Forty-three psoriasis patients without arthritis and 41 healthy controls were enrolled. All patients were <50 years, and women were premenopausal. Participants were questioned about demographic features, sun exposure, regular physical exercise, and smoking status. The serum levels of 25-OH vitamin D, calcium, phosphorus, C reactive protein, parathyroid hormone, total alkaline phosphatase, and sedimentation rate were measured. Body mass index was calculated. We determined the bone mineral density of the lumbar spine and femur using dual-energy X-ray absorptiometry. RESULTS: Femur neck Z score and lumbar spine total Z score were lower in psoriasis group than those of the control group. Additionally, total femoral Z score, lumbar spine total T, and Z scores were lower in female patients with psoriasis than female controls, whereas for male subjects there was not a remarkable difference between the groups. There was no significant difference between the two groups regarding vitamin D levels. The latter was significantly lower in psoriasis group than in controls for females; however, there was no significant difference between the two groups of males. Patients with psoriasis had higher CRP level and sedimentation rate, than control subjects. Female patients had also higher CRP level and sedimentation rate, than female controls, but there were no significant differences between male patients and controls. CONCLUSION: As osteoporosis has multifactorial etiology, psoriasis may be among the triggering or facilitating factors for osteoporosis particularly in psoriatic women via several mechanisms such as low blood level of vitamin D and increased inflammation. PMID- 26869074 TI - beta-catenin and Kras/Foxm1 signaling pathway are critical to restrict Sox9 in basal cells during pulmonary branching morphogenesis. AB - BACKGROUND: Lung morphogenesis is regulated by interactions between the canonical Wnt/beta-catenin and Kras/ERK/Foxm1 signaling pathways that establish proximal peripheral patterning of lung tubules. How these interactions influence the development of respiratory epithelial progenitors to acquire airway as compared to alveolar epithelial cell fate is unknown. During branching morphogenesis, SOX9 transcription factor is normally restricted from conducting airway epithelial cells and is highly expressed in peripheral, acinar progenitor cells that serve as precursors of alveolar type 2 (AT2) and AT1 cells as the lung matures. RESULTS: To identify signaling pathways that determine proximal-peripheral cell fate decisions, we used the SFTPC gene promoter to delete or overexpress key members of Wnt/beta-catenin and Kras/ERK/Foxm1 pathways in fetal respiratory epithelial progenitor cells. Activation of beta-catenin enhanced SOX9 expression in peripheral epithelial progenitors, whereas deletion of beta-catenin inhibited SOX9. Surprisingly, deletion of beta-catenin caused accumulation of atypical SOX9 positive basal cells in conducting airways. Inhibition of Wnt/beta-catenin signaling by Kras(G12D) or its downstream target Foxm1 stimulated SOX9 expression in basal cells. Genetic inactivation of Foxm1 from Kras(G12D) -expressing epithelial cells prevented the accumulation of SOX9-positive basal cells in developing airways. CONCLUSIONS: Interactions between the Wnt/beta-catenin and the Kras/ERK/Foxm1 pathways are essential to restrict SOX9 expression in basal cells. Developmental Dynamics 245:590-604, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26869075 TI - Dynamic mesolimbic dopamine signaling during action sequence learning and expectation violation. AB - Prolonged mesolimbic dopamine concentration changes have been detected during spatial navigation, but little is known about the conditions that engender this signaling profile or how it develops with learning. To address this, we monitored dopamine concentration changes in the nucleus accumbens core of rats throughout acquisition and performance of an instrumental action sequence task. Prolonged dopamine concentration changes were detected that ramped up as rats executed each action sequence and declined after earned reward collection. With learning, dopamine concentration began to rise increasingly earlier in the execution of the sequence and ultimately backpropagated away from stereotyped sequence actions, becoming only transiently elevated by the most distal and unexpected reward predictor. Action sequence-related dopamine signaling was reactivated in well trained rats if they became disengaged in the task and in response to an unexpected change in the value, but not identity of the earned reward. Throughout training and test, dopamine signaling correlated with sequence performance. These results suggest that action sequences can engender a prolonged mode of dopamine signaling in the nucleus accumbens core and that such signaling relates to elements of the motivation underlying sequence execution and is dynamic with learning, overtraining and violations in reward expectation. PMID- 26869076 TI - Investigating the feasibility and acceptability of a cognitive behavioural suicide prevention therapy for people in acute psychiatric wards (the 'INSITE' trial): study protocol for a randomised controlled trial. AB - BACKGROUND: Suicide is a major cause of preventable death, and suicidal behaviour is prevalent in acute psychiatric wards. People admitted to acute psychiatric wards often experience repeated episodes of suicidal behaviour, causing great distress and heavy use of NHS services. There is little research investigating effective psychological treatments for suicidal patients in inpatient settings although previous research has found support for psychological therapies which specifically target suicidal behaviour. This paper describes the protocol of a single blind RCT to investigate the acceptability and feasibility of a cognitive behavioural intervention targeting suicidality (CBSP) for suicidal people in acute psychiatric wards. METHODS/DESIGN: A single blind RCT comparing treatment as usual (TAU) to TAU plus Cognitive Behavioural Suicide Prevention (CBSP) therapy (TAU + CBSP). Sixty participants (aged 18-65 years) who are suicidal, or have been within the past 3 months, will be recruited from NHS trusts in the North West of England. Our primary objective is to determine whether CBSP is feasible, acceptable and efficacious when compared to patients who receive TAU alone. Secondary aims are the impact of CBSP on suicidal thinking, behaviours, functioning, quality of life, service use and psychological factors associated with suicide. Assessments take place at baseline, 6 weeks and 6 months (end of treatment). The analysis will report on the feasibility and acceptability of CBSP. Qualitative data from staff and service users will inform feasibility and acceptability data. DISCUSSION: Psychiatric inpatients are a high-risk group and the use of psychological therapies in these settings is rare and requires evaluation. This study is essential to investigate the unique contextual challenges involved in delivering psychological therapy to suicidal inpatients and to identify any necessary modifications required within inpatient settings. The findings will inform a larger, definitive trial. TRIAL REGISTRATION: 15 March 2012, PB-PG-1111-26026, NIHR ISRCTN17890126 . PMID- 26869077 TI - Cervical cages placed bilaterally in the facet joints from a posterior approach significantly increase foraminal area. AB - PURPOSE: Foraminal stenosis is a common cause of cervical radiculopathy. Posterior cervical cages can indirectly increase foraminal area and decompress the nerve root. The aim of this study was to assess the influence of bilateral posterior cervical cages on the surface area and shape of the neural foramen. METHODS: Radiographic analysis was performed on 43 subjects enrolled in a prospective, multi-center study. CT scans were obtained at baseline and 6- and 12 months after cervical fusion using bilateral posterior cervical cages. The following measurements were performed on CT scan: foraminal area (A), theoretical area (TA), height (H), superior diagonal (DSI), inferior diagonal (DIS), and inferior diagonal without implant (DISI). Comparisons were performed using R ANOVA with a significance of alpha < 0.05. RESULTS: Foraminal area, height, TA and DISI were significantly greater following placement of the implant. The mean (SD) A increased from 4.01 (1.09) mm(2) before surgery to 4.24 (1.00) mm(2) at 6 months, and 4.18 (1.05) mm(2) at 12 months after surgery (p < 0.0001). Foraminal height (H) increased from mean (SD) 9.20 (1.08) mm at baseline to 9.65 (1.06) mm and 9.55 (1.14) mm at 6- and 12-months post-operatively, respectively (p < 0.0001). The mean DIS did not change significantly. There was a significant decrease in DSI: 6.18 (1.59) mm pre-operatively, 5.95 (1.47) mm and 5.73 (1.46) mm at 6- and 12-months (p < 0.0001). CONCLUSIONS: Implantation of bilateral posterior cervical cages can increase foraminal area and may indirectly decompress the nerve roots. Correlation between increase in foraminal area and clinical outcomes needs further investigation. PMID- 26869078 TI - A RCT comparing 7-year clinical outcomes of one level symptomatic cervical disc disease (SCDD) following ProDisc-C total disc arthroplasty (TDA) versus anterior cervical discectomy and fusion (ACDF). AB - PURPOSE: The objective of this trial was to compare the safety and efficacy of TDA using the ProDisc-C implant to ACDF in patients with single-level SCDD between C3 and C7. METHODS: We report on the single-site results from a larger multicenter trial of 13 sites using an approved US Food and Drug Administration protocol (prospective, randomized controlled non-inferiority design). Patients were randomized one-to-one to either the ProDisc-C device or ACDF. All enrollees were evaluated pre- and post-operatively at regular intervals through month 84. Visual Analog Scale (VAS) for neck and arm pain/intensity, Neck Disability Index (NDI), Short-Form 36 (SF-36), and satisfaction were assessed. RESULTS: Twenty-two patients were randomized to each arm of the study. Nineteen additional patients received the ProDisc-C via continued access. NDI improved with the ProDisc-C more than with ACDF. Total range of motion was maintained with the ProDisc-C, but diminished with ACDF. Neck and arm pain improved more in the ProDisc-C than ACDF group. Patient satisfaction remained higher in the ProDisc-C group at 7 years. SF 36 scores were higher in the TDA group than ACDF group at 7 years; the difference was not clinically significant. Six additional operations (two at the same level; four at an adjacent level) were performed in the ACDF, but none in the ProDisc-C group. CONCLUSIONS: The ProDisc-C implant appears to be safe and effective for the treatment of SCDD. Patients with the implant retained motion at the involved segment and had a lower reoperation rate than those with an ACDF. PMID- 26869079 TI - Publication rate of paper and podium presentations from the European Section of the Cervical Spine Research Society Annual Meeting. AB - PURPOSE: The Cervical Spine Research Society Europe (CSRS-E) actively promotes scientific activities, the annual meeting being the most evident of them. The publication rate of oral and poster presentations at the annual meeting could be a measure for the success of the promotional activities. The publication rates of abstracts presented at the annual European meetings of the CSRS are unknown. The quality of the abstracts presented at a conference is reflected by the publication rate. A high publication rate is usually interpreted as representative of high scientific value of the conference. METHODS: Poster and podium presentations from the 2007 to 2012 annual meetings were identified. Pubmed was used to search for the abstract title and/or the combination of authors to verify whether the data were published in a peer-reviewed journal. Abstracts were considered published if the data presented at the meeting were identical to that in the publication. The journals in which the data were published were identified, as well as the origin of the research centre. RESULTS: From 2007 to 2012 826 abstracts were featured at the CSRS Europe annual meetings. There were 236 podium presentations and 590 poster presentations. 42 % of the podium presentations resulted in a publication, and 28 % of the poster presentations led to a publication. Overall, 32 % of accepted abstracts effectuated a publication in a peer-reviewed scientific journal. Abstracts from European research groups had a publication rate of 29 % compared to 34 % for abstracts from non-European research groups. Spine, European Spine Journal, Journal of Spinal Disorders and Techniques and J Neurosurgery Spine were the most common publication journals for the abstracts. The mean impact factor of the journals in which was published was 2.2. CONCLUSION: 42 % of the abstracts that were accepted for podium presentation at the CSRS Europe resulted in a publication in peer-reviewed MEDLINE indexed journals. Publication rates are at the high end of the publication rate spectrum of abstracts accepted for European scientific meetings. PMID- 26869081 TI - Development of a heat-mediated protein blotting method. AB - Western blotting is a significant tool employed for the detection of cell proteins. High-molecular-weight proteins have proven a challenge to detect by western blotting, but proteins even of 100 KDa can still present difficulties in detection. This work reports the development of a heat transfer method that is suitable for both low- and high-molecular-weight proteins. The procedure involves the use of a constant temperature at 78 degrees C in a dedicated heat transfer module. Through the use of this protocol the neuronal adaptor protein X11alpha (120 KDa), which prior to this methodology was undetectable endogenously in the neuroblastoma cell line (N2a), was successfully detected in the N2a cell line. The procedure provides a reproducible protocol that can be adapted for other high molecular-weight proteins, and it provides the advantage that low-molecular weight proteins are not sacrificed by the methodology. PMID- 26869082 TI - A label-free turn-on fluorescence probe for rapidly distinguishing cysteine over glutathione in water solution. AB - A novel label-free fluorescent chemodosimeter (C1) was synthesized, based on coumarin and N-(4-aminobenzoyl)-beta-alanine, for the selective detection of cysteine (Cys) over glutathione (GSH), which involved a click reaction of Cys to CN of a Schiff base. The probe C1 featured a fast response (about 3 min), emission in the visible region, and high selectivity. Addition of Cys in HEPES NaOH solution (pH 7.4) to C1 in water resulted in the appearance of a new emission peak at 445 nm, in company with remarkable enhancement of fluorescence intensity, while other amino acids did not induce any significant fluorescence change. Meanwhile, the addition reaction of Cys to C1 elicited 90.8-fold fluorescence intensity enhancement, which resulted in a change of emission color from orange to blue. PMID- 26869083 TI - Optimization of surface plasmon resonance experiments: Case of high mobility group box 1 (HMGB1) interactions. AB - Surface plasmon resonance (SPR) is a powerful technique for evaluating protein protein interactions in real time. However, inappropriately optimized experiments can often lead to problems in the interpretation of data, leading to unreliable kinetic constants and binding models. Optimization of SPR experiments involving "sticky" proteins, or proteins that tend to aggregate, represents a typical scenario where it is important to minimize errors in the data and the kinetic analysis of those data. This is the case of High Mobility Group Box 1 and the receptor of advanced glycation end products. A number of improvements in protein purification, buffer composition, immobilization conditions, and the choice of flow rate are shown to result in substantial improvements in the accurate characterization of the interactions of these proteins and the derivation of the corresponding kinetic constants. PMID- 26869084 TI - An electrochemical aptasensor electrocatalyst for detection of thrombin. AB - This work reports a novel signal amplification strategy based on three dimensional ordered macroporous C60-poly(3,4-ethylenedioxythiophene)-1-butyl-3 methylimidazolium hexafluorophosphate (3DOM C60-PEDOT-[BMIm][BF6]) for ultrasensitive detection of thrombin by cascade catalysis of Au-PEDOT@SiO2 microspheres and alcohol dehydrogenase (ADH). Au-PEDOT@SiO2 microspheres were constructed not only as nanocarriers to anchor the large amounts of secondary thrombin aptamers but also as nanocatalysts to catalyze the oxidation of ethanol efficiently. Significantly, the electrochemical signal was greatly enhanced based on cascade catalysis: First, ADH catalyzed the oxidation of ethanol to acetaldehyde with the concomitant generation of NADH in the presence of beta nicotinamide adenine dinucleotide hydrate (NAD(+)). Then, gold nanoparticles (AuNPs) as nanocatalysts could effectively catalyze NADH to produce NAD(+) with the help of PEDOT as redox probe. Under the optimal conditions, the proposed aptasensor exhibits a linear range of 2 * 10(-13) to 2 * 10(-8) M with a low detection limit of 2 * 10(-14) M for thrombin detection and shows high sensitivity and good specificity. PMID- 26869085 TI - Cellular signalling of cysteinyl leukotriene type 1 receptor variants CysLT1 G300S and CysLT1-I206S. AB - Cysteinyl-leukotrienes are pro-inflammatory lipid mediators, involved in allergic asthma, that bind the G-protein-coupled receptors CysLT1, CysLT2 and GPR99. A polymorphism in one of these receptors, CysLT1-G300S was strongly associated with atopy, whereas the CysLT1-I206S polymorphism was not. In the present work, our aim was to characterize these two variants by studying their cellular signalling. Cell surface expression of mutant receptors in transfected HEK-293 cells was comparable to that of the wild-type receptor. Compared to CysLT1-WT, production of inositol phosphates as well as IL-8 and IL-13 promoter transactivation in response to either LTD4 or LTC4 was significantly increased in CysLT1-G300S transfected cells. Moreover, LTD4-induced phosphorylation of the signalling effector Erk, but not p38, p65 or c-Jun was higher in CysLT1-G300S-transfected cells. On the other hand, the variant CysLT1-I206S did not show a significant difference in its signal transduction compared to the wild-type receptor. Taken together, our results indicate that the variant CysLT1-G300S can induce a greater signal than the CysLT1-WT receptor, a feature that may be relevant to its association with atopy. PMID- 26869086 TI - Associations between a fatty acid desaturase gene polymorphism and blood arachidonic acid compositions in Japanese elderly. AB - We investigated whether the single nucleotide polymorphism rs174547 (T/C) of the fatty acid desaturase-1 gene, FADS1, is associated with changes in erythrocyte membrane and plasma phospholipid (PL) long-chain polyunsaturated fatty acid (LCPUFA) composition in elderly Japanese participants (n=124; 65 years or older; self-feeding and oral intake). The rs174547 C-allele carriers had significantly lower arachidonic acid (ARA; n-6 PUFA) and higher linoleic acid (LA, n-6 PUFA precursor) levels in erythrocyte membrane and plasma PL (15% and 6% ARA reduction, respectively, per C-allele), suggesting a low LA to ARA conversion rate in erythrocyte membrane and plasma PL of C-allele carriers. alpha-linolenic acid (n-3 PUFA precursor) levels were higher in the plasma PL of C-allele carriers, whereas levels of the n-3 LCPUFAs eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) were unchanged in erythrocyte membrane and plasma PL. Thus, rs174547 genotypes were significantly associated with different ARA compositions of the blood of elderly Japanese. PMID- 26869087 TI - Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial. AB - We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377. PMID- 26869089 TI - Association between breast milk fatty acids and HIV-1 transmission through breastfeeding. AB - A residual mother-to-child transmission of HIV through breastfeeding persists despite prophylaxis. We identified breast milk fatty acids (FA) associated with postnatal HIV transmission through breastfeeding in a case-control study. Cases (n=23) were HIV-infected women with an infant who acquired HIV after 6 weeks of age. Controls (n=23) were matched on infant's age at sample collection. Adjusting for maternal antenatal plasma CD4 T cell count, cis-vaccenic acid (18:1n-7) and eicosatrienoic acid (20:3n-3) were associated with HIV transmission in opposite dose-response manner: OR (tertile 3 versus tertile 1): 10.8 and 0.16, p for trend=0.02 and 0.03, respectively. These fatty acids correlated with HIV RNA load, T helper-1 related cytokines, IL15, IP10, and beta2 microglobulin, positively for cis-vaccenic acid, negatively for eicosatrienoic acid. These results suggested a change in FA synthesis by mammary gland cells leading to increased cis-vaccenic acid in milk of mothers who transmitted HIV to their infant during breastfeeding. PMID- 26869093 TI - Image-Guided Development of Biomaterials: Enabling Technologies Shaping and Expediting the Future of Materials in Medicine. PMID- 26869088 TI - Threshold changes in rat brain docosahexaenoic acid incorporation and concentration following graded reductions in dietary alpha-linolenic acid. AB - BACKGROUND: This study tested the dietary level of alpha-linolenic acid (alpha LNA, 18:3n-3) required to maintain brain (14)C-Docosahexaenoic acid (DHA, 22:6n 3) metabolism and concentration following graded alpha-LNA reduction. METHODS: Fischer-344 (CDF) male rat pups (18-21 days old) were randomized to the AIN-93G diet containing as a % of total fatty acids, 4.6% ("n-3 adequate"), 3.6%, 2.7%, 0.9% or 0.2% ("n-3 deficient") alpha-LNA for 15 weeks. Rats were intravenously infused with (14)C-DHA to steady state for 5 min, serial blood samples collected to obtain plasma, and brains excised following microwave fixation. Labeled and unlabeled DHA concentrations were measured in plasma and brain to calculate the incorporation coefficient, k*, and incorporation rate, J(in). RESULTS: Compared to 4.6% alpha-LNA controls, k* was significantly increased in ethanolamine glycerophospholipids in the 0.2% alpha-LNA group. Circulating unesterified DHA and brain incorporation rates (J(in)) were significantly reduced at 0.2% alpha LNA. Brain total lipid and phospholipid DHA concentrations were reduced at or below 0.9% alpha-LNA. CONCLUSION: Threshold changes for brain DHA metabolism and concentration were maintained at or below 0.9% dietary alpha-LNA, suggesting the presence of homeostatic mechanisms to maintain brain DHA metabolism when dietary alpha-LNA intake is low. PMID- 26869094 TI - Water flux management and phytoplankton communities in a Mediterranean coastal lagoon. Part I: How to promote dinoflagellate dominance? AB - The Biguglia lagoon is a shallow Mediterranean coastal ecosystem where eutrophication is increasing for years. A channel supplying freshwater was cleared in 2009 to enhance lagoon water circulation and alleviate dystrophic crises. Monthly monitoring was started in 2010 to document the impacts of this action on abiotic characteristics and phytoplankton communities. Three stations were surveyed (by microscopy and HPLC). Evidence suggests that this operation had an unexpected outcome. Salinity footprints indicated the succession of three main hydrological sequences that depended on rainfall and circulation pattern. Diatoms and dinoflagellates dominated the first sequence, characterized by heavy rainfall, while Prorocentrum minimum became progressively the dominant species in the second period (increasing salinities) with extensive bloom over the whole lagoon (5.93*10-(5) cells.L(-1)) during the third period. These phytoplankton successions and community structures underline the risk of pernicious effects arising from remediation efforts, in the present case based on increasing freshwater inputs. PMID- 26869095 TI - Suspended particulate matter fluxes along with their associated metals, organic matter and carbonates in a coastal Mediterranean area affected by mining activities. AB - A study of suspended particulate matter (SPM) fluxes along with their associated metals, organic matter and carbonates, was conducted off the Mejerda River outlet in May 2011 and in March and July 2012 at depths of 10, 20 and 40 m using sediment traps. SPM fluxes are more significant near the Mejerda outlet, especially in winter, but dissipate further offshore. Normalization reveals that the Mejerda is a major source of Pb, Zn, Cd, Cu, Ni, and Co, all of which are the result of human activities. In contrast, Fe, Mn and N are of authigenic origin. The enrichment factor shows that Pb, Zn and especially Cd are the most highly polluting metals off the Mejerda outlet. This confirms the trend observed on the shores of the Mejerda prodelta and is consistent with the type of mining activities conducted in the Mejerda catchment. PMID- 26869096 TI - Mechanisms of cephalosporin resistance in indicator Escherichia coli isolated from food animals. AB - Resistance to beta-lactams is considered one of the major global problems and recently it became the most frequently studied topic in the area of antimicrobial resistance. The study was focused on phenotypic and genetic characterisation of commensal Escherichia coli (E. coli), including those producing cephalosporinases, isolated from gut flora of healthy slaughter animals. E. coli were cultured simultaneously on MacConkey agar (MCA) and cefotaxime supplemented MCA. The isolates were confirmed with ONPG and indol tube tests as well as PCR targeting uspA gene. Microbroth dilution method was applied for determination of Minimal Inhibitory Concentrations and interpreted according to EUCAST epidemiological cut-off values. Cephalosporin resistance phenotypes were defined by E-tests (BioMerieux) and relevant gene amplicons from selected strains were sequenced. A total of 298 E. coli isolates with cephalosporin resistance (ESC) found in 99 ones, were obtained from 318 cloacal or rectal swabs deriving from broilers, layers, turkeys, pigs and cattle. Both extended spectrum beta-lactamase (ESBL) and ampC-cephalosporinase resistance phenotypes were noted in all tested animal species but cattle. At least one of the analysed genes was identified in 90 out of 99 cephalosporin-resistant isolates: blaTEM (n=44), blaCMY (n=38), blaCTX-M (n=33) and blaSHV (n=12). None of the phenotypes was identified in nine isolates. Sequencing of PCR products showed occurrence of ESBL-genes: blaCTX-M-1/ 61, blaSHV-12, blaTEM-1,-52/-92,-135 and ampC-gene blaCMY-2. They were located on numerous and diverse plasmids and resistance transferability was proved by electroporation of blaSHV-12 and blaCTX-M-1/-61 located on X1 plasmids. Detection of cephalosporin resistant E. coli confirms the existence of resistance genes reservoir in farm animals and their possible spread (i.e. via IncX1 plasmids) to other bacteria including human and animal pathogens. The identified genetic background indicates on ecological aspects of selection and dissemination of cephalosporin resistance in E. coli isolated from food-producing animals rather than its potential role for public health threats. PMID- 26869097 TI - MRSA in equine hospitals and its significance for infections in humans. AB - MRSA infections in equine clinics were reported from Northern America, Europe, Australia, and Japan. The majority of nosocomial infections in horses is obviously associated with particular MRSA clonal lineages. As already observed for epidemic MRSA in human hospitals more than 10 years ago, a dynamics of MRSA clonal lineages is also observed in European equine clinics: clonal lineages belonging to clonal complex (CC) 8 are on the retreat whereas MRSA attributed to CC398 become increasingly prevalent. The majority of CC398 isolates belong to a subpopulation which is particularly associated with equine hospitals as indicated by molecular typing. When emerging in equine clinics, MRSA from horses were also found as nasal colonizers of veterinary personnel. MRSA exhibiting the typing characteristics of MRSA known from equine clinics are obviously rare among MRSA from infections in humans. Although rare so far epidemic MRSA from human hospitals (HA-MRSA, e.g., ST22, ST225) have been isolated from nosocomial infections in horses and need particular attention in further surveillance. PMID- 26869098 TI - Synthesis of octahedral, truncated octahedral, and cubic Rh2Ni nanocrystals and their structure-activity relationship for the decomposition of hydrazine in aqueous solution to hydrogen. AB - We developed a co-reduction method to synthesize octahedral, truncated octahedral, and cubic Rh2Ni nanocrystals. The shape/size distribution, structural characteristics, and composition of the Rh2Ni nanocrystals are investigated, and their possible formation mechanism at high temperatures in margaric acid/1 aminoheptadecane solution in the presence of tetraethylgermanium and borane trimethylamine complexes is proposed. A preliminary probing of the structure activity dependence of the surface "clean" Rh2Ni nanocrystals supported on carbon towards hydrazine (N2H4) in aqueous solution dehydrogenation revealed that the higher the percentage of {111} facets, the higher is the activity and H2 selectivity of the nanocrystals. This result was attributed to the {111} facets not only introducing more basic sites, but also weakening the interaction between the produced adspecies (including H2 and NHx) and surface metal atoms in comparison with those of {100} facets. Furthermore, the as-prepared Rh2Ni nanooctahedra exhibited 100% H2 selectivity and high activity at room temperature for H2 generation via N2H4 decomposition. The activation energy of the Rh2Ni nanooctahedra was 41.6 +/- 1.2 kJ mol(-1). The Rh2Ni nanooctahedra were stable catalysts for the hydrolytic dehydrogenation of N2H4, providing 27 723 total turnovers in 30 h. Our work provides a new perspective concerning the possibility of constructing hydrogen-producing systems based on N2H4 and surface "clean" Rh2Ni nanocrystal catalysts with defined shapes supported on carbon that possess a competitive performance in comparison with NaBH4 and NH3BH3 hydrogen-producing systems for fuel cell applications. PMID- 26869099 TI - Cytotoxic nor-dammarane triterpenes from Viburnum hainanense Merr. et Chun. AB - Five new nor-dammarane triterpenes, 12beta-O-acetyl-17beta-hydoxy-3,15-dioxo 20,21,22,23,24,25,26,27-octanordammanran (1), 12beta-hydoxy-17beta-methoxy-3,15 dioxo-20,21,22,23,24,25,26,27-octanordammanran (2), 12beta-O-acetyl-3,15-dioxo-17 en-20,21,22,23,24,25,26,27-octanordammanran (3), 12beta-hydoxy-15alpha-O-acetyl-3 oxo-17-en-20,21,22,23,24,25,26,27-octanordammanran (4) and 3beta-hydoxy-17-oxo-12 en-20,21,22,23,24,25,26,27-octanordammanran (5), were obtained from the ethanol extract of the whole plants of Viburnum hainanense Merr. et Chun. Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic potential against seven tumor cell lines (Hep-2, SCL-1, CAL-27, UMSCC 1, Detroit-562, SCC-PKU, and TCA-83). As result, compounds 1 and 2 exhibited cytotoxic activities with IC50 values less than 10 MUM. PMID- 26869101 TI - New Biological Insights from Better Structure Models. AB - Structure validation is a key component of all steps in the structure determination process, from structure building, refinement, deposition, and evaluation all the way to post-deposition optimisation of structures in the Protein Data Bank (PDB) by re-refinement and re-building. Today, many aspects of protein structures are understood better than 10years ago, and combined with improved software and more computing power, the automated PDB_REDO procedure can significantly improve about 85% of all X-ray structures ever deposited in the PDB. We review structure validation, structure improvement, and a series of validation resources and facilities that give access to improved PDB files and to reports on the quality of the original and the improved structures. Post deposition optimisation generally leads to improved protein structures and a series of examples will illustrate how that, in turn, leads to improved or even novel biological insights. PMID- 26869100 TI - Changes in membrane sphingolipid composition modulate dynamics and adhesion of integrin nanoclusters. AB - Sphingolipids are essential constituents of the plasma membrane (PM) and play an important role in signal transduction by modulating clustering and dynamics of membrane receptors. Changes in lipid composition are therefore likely to influence receptor organisation and function, but how this precisely occurs is difficult to address given the intricacy of the PM lipid-network. Here, we combined biochemical assays and single molecule dynamic approaches to demonstrate that the local lipid environment regulates adhesion of integrin receptors by impacting on their lateral mobility. Induction of sphingomyelinase (SMase) activity reduced sphingomyelin (SM) levels by conversion to ceramide (Cer), resulting in impaired integrin adhesion and reduced integrin mobility. Dual colour imaging of cortical actin in combination with single molecule tracking of integrins showed that this reduced mobility results from increased coupling to the actin cytoskeleton brought about by Cer formation. As such, our data emphasizes a critical role for the PM local lipid composition in regulating the lateral mobility of integrins and their ability to dynamically increase receptor density for efficient ligand binding in the process of cell adhesion. PMID- 26869102 TI - Transparency in a world of complexity: Basic guidelines for improved statistical reporting. PMID- 26869105 TI - Editorial: The Journal of Dairy Research. PMID- 26869104 TI - VRK1 phosphorylates and protects NBS1 from ubiquitination and proteasomal degradation in response to DNA damage. AB - NBS1 is an early component in DNA-Damage Response (DDR) that participates in the initiation of the responses aiming to repair double-strand breaks caused by different mechanisms. Early steps in DDR have to react to local alterations in chromatin that are induced by DNA damage. NBS1 participates in the early detection of DNA damage and functions as a platform for the recruitment and assembly of components that are sequentially required for the repair process. In this work we have studied whether the VRK1 chromatin kinase can affect the activation of NBS1 in response to DNA damage induced by ionizing radiation. VRK1 is forming a basal preassembled complex with NBS1 in non-damaged cells. Knockdown of VRK1 resulted in the loss of NBS1 foci induced by ionizing radiation, an effect that was also detected in cell-cycle arrested cells and in ATM (-/-) cells. The phosphorylation of NBS1 in Ser343 by VRK1 is induced by either doxorubicin or IR in ATM (-/-) cells. Phosphorylated NBS1 is also complexed with VRK1. NBS1 phosphorylation by VRK1 cooperates with ATM. This phosphorylation of NBS1 by VRK1 contributes to the stability of NBS1 in ATM (-/-) cells, and the consequence of its loss can be prevented by treatment with the MG132 proteasome inhibitor of RNF8. We conclude that VRK1 regulation of NBS1 contributes to the stability of the repair complex and permits the sequential steps in DDR. PMID- 26869103 TI - Grb7 and Hax1 may colocalize partially to mitochondria in EGF-treated SKBR3 cells and their interaction can affect Caspase3 cleavage of Hax1. AB - Growth factor receptor bound protein 7 (Grb7) is a signal-transducing adaptor protein that mediates specific protein-protein interactions in multiple signaling pathways. Grb7, with Grb10 and Grb14, is members of the Grb7 protein family. The topology of the Grb7 family members contains several protein-binding domains that facilitate the formation of protein complexes, and high signal transduction efficiency. Grb7 has been found overexpressed in several types of cancers and cancer cell lines and is presumed involved in cancer progression through promotion of cell proliferation and migration via interactions with the erythroblastosis oncogene B 2 (human epidermal growth factor receptor 2) receptor, focal adhesion kinase, Ras-GTPases, and other signaling partners. We previously reported Grb7 binds to Hax1 (HS1 associated protein X1) isoform 1, an anti-apoptotic protein also involved in cell proliferation and calcium homeostasis. In this study, we confirm that the in vitro Grb7/Hax1 interaction is exclusive to these two proteins and their interaction does not depend on Grb7 dimerization state. In addition, we report Grb7 and Hax1 isoform 1 may colocalize partially to mitochondria in epidermal growth factor-treated SKBR3 cells and growth conditions can affect this colocalization. Moreover, Grb7 can affect Caspase3 cleavage of Hax1 isoform 1 in vitro, and Grb7 expression may slow Caspase3 cleavage of Hax1 isoform 1 in apoptotic HeLa cells. Finally, Grb7 is shown to increase cell viability in apoptotic HeLa cells in a time-dependent manner. Taken together, these discoveries provide clues for the role of a Grb7/Hax1 protein interaction in apoptosis pathways involving Hax1. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26869106 TI - Genetically engineering milk. AB - It has been thirty years since the first genetically engineered animal with altered milk composition was reported. During the intervening years, the world population has increased from 5bn to 7bn people. An increasing demand for protein in the human diet has followed this population expansion, putting huge stress on the food supply chain. Many solutions to the grand challenge of food security for all have been proposed and are currently under investigation and study. Amongst these, genetics still has an important role to play, aiming to continually enable the selection of livestock with enhanced traits. Part of the geneticist's tool box is the technology of genetic engineering. In this Invited Review, we indicate that this technology has come a long way, we focus on the genetic engineering of dairy animals and we argue that the new strategies for precision breeding demand proper evaluation as to how they could contribute to the essential increases in agricultural productivity our society must achieve. PMID- 26869107 TI - Minor milk constituents are affected by protein concentration and forage digestibility in the feed ration. AB - The present study was conducted in order to investigate if selected minor milk components would be indicative for the nutritional situation of the cow. Forty eight dairy cows were offered a high digestible ration vs. a lower digestible ration combined with 2 protein levels in a 4 * 4 Latin square design. Milk glucose, glucose-6-phosphate, cholesterol, triacylglycerides (TAG), uric acid and beta-hydroxybutyrate (BHBA) were measured and correlated mutually and towards other milking parameters (yield, h since last milking, days in milk (DIM), urea, etc). The variation range of the suggested variables were broad, a fact that may support their utilisation as predictive parameters. The content of milk metabolites was significantly affected by the change in rations as milk glucose, glucose-6-phosphate, uric acid, and the ratio cholesterol: triacylglycerides increased with higher energy intake while BHBA and TAG decreased. The content of some of the milk metabolites changed during 24 h day/night periods: BHBA, cholesterol, uric acid and TAG increased whereas free glucose decreased in the night period. Certain associations between milk metabolites and calculated energy parameters like ECM, body condition score (BCS), and body weight gain were found, however, these associations were to some extent explained by an interaction with DIM, just as changes in milk metabolites during a 24 h period seems to interfere. It is concluded that the practical use of the suggested milk variables should be based on more than one metabolite and that stage of lactation and possibly time of the day where the milk is collected should be incorporated in predictive models. PMID- 26869108 TI - Effects of alpha-linolenic acid-enriched diets on gene expression of key inflammatory mediators in immune and milk cells obtained from Holstein dairy cows. AB - Immune system and inflammatory responses are affected by alpha-linolenic acid (alphaLA: 18:3 omega-3). The objective of this study was to determine the effects of alphaLA-enriched rations on gene expression of systemic (blood) and local (mammary gland) inflammatory markers in Holstein dairy cattle. Further, the effect of dietary treatments was evaluated on the concentration of alphaLA in serum phospholipids. Camelina (Camelina sativa) meal (containing 24.2% alphaLA) was fed at 0, 3, 6, and 9% (dry matter basis) replacing canola meal (rich in 18:1 omega-9) to provide rations with incremental concentrations of alphaLA. Lactating primiparous Holstein cows (n = 18) were randomly assigned to a treatment sequence in a 4 * 4 Latin square design. Each period lasted 16 d and milk and blood samples were collected during the final 2 d of each period. Peripheral blood mononuclear cells (PBMC) and milk cells (MC) were harvested, and RNA extracted and converted to complementary DNA for quantitative real time PCR analysis. The effect of dietary treatments (alphaLA) on the relative abundance of pro- and anti inflammatory genes in the PBMC and MC was tested by the MIXED procedure of SAS. Expression of pro-inflammatory tumour necrosis factor (TNF)-alpha in MC was linearly reduced (up to 40%) as dietary alphaLA increased. Expression of pro inflammatory markers interleukin (IL)-1beta, IL-8, and TNF-alpha was reduced (29, 20, and 27%, respectively) in PBMC isolated from cows fed 6% camelina meal ration as compared with cows fed 0% (control). Expression of IL-6 was, however, increased with inclusion of camelina meal. Greater dietary alphaLA linearly increased serum phospholipids alphaLA contents, and when fed up to 6% DM down regulated expression of some of the local (milk) and systemic (blood) pro inflammatory markers in vivo. PMID- 26869109 TI - Effect of ruminally unprotected Echium oil on milk yield, composition and fatty acid profile in mid-lactation goats. AB - This study investigated the effects on goat milk yield and composition of a diet supplemented with Echium plantagineum oil (EPO). Twenty-four mid-lactation multiparous Camosciata goats were divided into two balanced groups and fed for 44 d a diet based on hay and concentrate, supplemented (EPO group, Echium) or not (CON group, control) with 40 ml of ruminally unprotected EPO. Individual milk yield was recorded and individual milk samples were collected at 11, 22, 33, and 44 d after supplementation. Milk samples were analysed for milk components and fatty acids (FA). Data were statistically analysed by repeated-measures analysis of variance. Milk yield, protein and lactose contents were significantly higher in EPO than CON group. The inclusion of EPO significantly decreased total saturated FA and total branched-chain FA, and contemporarily sharply increased trans biohydrogenation intermediates (P ? 0.001). Milk concentration of alpha linolenic, stearidonic and gamma-linolenic acids increased by 23, 1000 and 67%, respectively (P ? 0.001). Due to extensive ruminal biohydrogenation, their apparent transfer rate was less than 3%. As a consequence, the milk concentrations of very long-chain (VLC) polyunsaturated fatty acids (PUFA), such as eicosapentaenoic (20:5 n-3) and dihomo-gamma-linolenic (20:3 n-6) acids, significantly increased with EPO treatment, but values remained very low. Docosahexaenoic acid (22:6 n-3) was undetectable in all analysed milk samples. Results show that ruminally unprotected EPO can enhance milk yield and protein and improve the overall goat milk FA profile. However, this kind of supplementation cannot be considered a valuable strategy to develop goat functional dairy products enriched with VLC n-3 PUFA for human consumption. PMID- 26869110 TI - Fatty acid profiles of milk and Minas frescal cheese from lactating grazed cows supplemented with peanut cake--ERRATUM. PMID- 26869111 TI - High levels of acetoacetate and glucose increase expression of cytokines in bovine hepatocytes, through activation of the NF-kappaB signalling pathway. AB - Elevated levels of blood interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) increase insulin resistance and result in inflammation. It is not clear whether elevated blood level of acetoacetate (ACAC) and decreased blood level of glucose, which are the predominant characteristics of clinical biochemistry in ketotic dairy cows, increase proinflammatory cytokines and subsequent inflammation. The objective of this study was to test the hypothesis that ACAC and glucose activate the NF-kappaB signalling pathway to regulate cytokines expression in bovine hepatocytes. Bovine hepatocytes were cultured with ACAC (0-4.8 mm) and glucose (0-5.55 mm) with or without NF-kappaB inhibitor PDTC for 24 h. The secretion and mRNA levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and real time fluorescence quantitative polymerase chain reaction (qRT-PCR). The NF-kappaB signalling pathway activation was evaluated by western blotting. Results showed that the secretion and expression of IL-1beta, IL-6 and TNF-alpha increased in an ACAC dose-dependent manner. Additionally, there was an increase in the secretion and mRNA expression of these three cytokines in glucose treatment group, which increased significantly when the glucose concentrations exceed 3.33 mm. Furthermore, both ACAC and glucose upregulated NF-kappaB p65 protein expression and IkappaBalpha phosphorylation levels. However, these effects were reduced by PDTC. These results demonstrate that elevated levels of ACAC and glucose increase the synthesis and expression of proinflammatory factors by activating NF-kappaB signalling pathway in hepatocytes, which may contribute to inflammation injury in ketotic dairy cows. PMID- 26869112 TI - Covariance structures of fat and protein influence the estimation of IgG in bovine colostrum. AB - On-farm instruments for assessing colostrum quality are needed in order to ensure that the calf is supplied with enough IgG to avoid failure of passive transfer. The aim of this study was to evaluate methods for estimating the IgG concentration in cows' colostrum. This research included 126 colostrum samples from 21 Danish farms with different breeds, ensuring a broad variation pattern in IgG, total protein and fat concentration. Approximately one third of the samples did not fulfil the recommendation of >50 g IgG/l colostrum, and the IgG concentration decreased with time from calving to milking. The ratio of IgG to total protein varied from 6 to 61%, however IgG and total protein were correlated with r2 = 0.70. The variation in fat was independent of variations in protein and IgG. The IgG concentration was measured by ELISA and compared to fast measurements by specific gravity by colostrometer, Brix by refractometer and prediction from infrared spectroscopy. The three fast methods were all correlated to the total protein concentration of colostrum; however specific gravity was also influenced by the fat concentration. Furthermore, specific gravity generally overestimated the IgG concentration, and the cut-off level should be raised to 1050 in order to ensure adequate IgG in colostrum. None of the methods estimated IgG concentration better than the correlation of total protein and IgG, meaning that they all depended on the indirect correlation between total protein and IgG. The results suggest that using a refractometer for quality control of colostrum is an easy and feasible method, and a cut-off level of Brix 22 seems sufficient to assure adequate IgG concentration in colostrum fed to the calf. PMID- 26869113 TI - Production and chemical composition of two dehydrated fermented dairy products based on cow or goat milk. AB - The aim of this study was to identify the differences between the main macro and micronutrients including proteins, fat, minerals and vitamins in cow and goat dehydrated fermented milks. Fermented goat milk had higher protein and lower ash content. All amino acids (except for Ala), were higher in fermented goat milk than in fermented cow milk. Except for the values of C11:0, C13:0, C16:0, C18:0, C20:5, C22:5 and the total quantity of saturated and monounsaturated fatty acids, all the other fatty acid studied were significantly different in both fermented milks. Ca, Mg, Zn, Fe, Cu and Se were higher in fermented goat milk. Fermented goat milk had lower amounts of folic acid, vitamin E and C, and higher values of vitamin A, D3, B6 and B12. The current study demonstrates the better nutritional characteristics of fermented goat milk, suggesting a potential role of this dairy product as a high nutritional value food. PMID- 26869114 TI - Comparative study of microbiological, chemical and sensory properties of kefirs produced in Estonia, Latvia and Lithuania. AB - In the current study the microbiological, sensory and chemical properties of 24 kefirs (12 producers) from Estonian, Latvian and Lithuanian retail market were determined using gas chromatography (GC), high performance liquid chromatography (HPLC-MS/MS-Q-TOF and LC-ion trap MS/MS), spectrophotometry and other methods. Antihypertensive, angiotensin-converting enzyme (ACE) inhibiting, antioxidant and antibacterial peptides were found in the kefir samples. According to the results of principal component analysis of 200 most abundant compounds obtained with HPLC MS/MS-Q-TOF analysis, Estonian kefirs differed from the rest. Kefirs of Latvian and Lithuanian origin showed similarities in several characteristics, probably related to the starter cultures and technological processes. The fatty acids composition of all Baltic kefirs was uniform. The antioxidant capacity of the kefirs varied slightly, whereas intermediate positive correlation (r = 0.32, P < 0.05) was found between antioxidativity and total bacterial count. The lipid oxidation level, estimated as the content of linoleic and oleic acid primary oxidation products, oxylipins, was very low in all studied kefirs. Only one third of analysed kefirs met the requirements of the minimum sum of viable microorganisms, indicated in the Codex Standard for Fermented Milks. PMID- 26869115 TI - Whey cheese: membrane technology to increase yields. AB - Sweet cheese whey has been used to obtain whey cheese without the addition of milk. Pre-treated whey was concentrated by nanofiltration (NF) at different concentration ratios (2, 2.5 and 2.8) or by reverse osmosis (RO) (2-3 times). After the concentration, whey was acidified with lactic acid until a final pH of 4.6-4.8, and heated to temperatures between 85 and 90 degrees C. The coagulated fraction (supernatant) was collected and freely drained over 4 h. The cheese-whey yield and protein, fat, lactose and ash recoveries in the final product were calculated. The membrane pre-concentration step caused an increase in the whey cheese yield. The final composition of products was compared with traditional cheese-whey manufacture products (without membrane concentration). Final cheese yields found were to be between 5 and 19.6%, which are higher than those achieved using the traditional 'Requeson' process. PMID- 26869117 TI - Introduction. PMID- 26869116 TI - Modulating the textural characteristics of whey protein nanofibril gels with different concentrations of calcium chloride. AB - Protein nanofibrils with 10-20 nm diameters were formed by heating whey protein solution at pH 2.0. Nanofibrils solution was deacidified slowly through dialysis followed by adding different amounts of CaCl2 (0-80 mM) into the dialysis water resulting in formation of a soft viscoelastic gel over time. The gel fabricated from the nanofibrils solution dialyzed against distilled water with 0 mM CaCl2 had zero ash content. Fourier transform infra-red spectroscopy revealed a change in the pattern of hydrogen bond formation in gel network by calcium chloride. The higher the ash content of gels, the lower was the storage modulus and fracture stress of samples. Gels with higher ash contents had a more porous microstructure which was attributed to the diminished hydrophobic interactions and hydrogen bonding among nanofibrils by the action of chloride. Higher ash contents also led to higher water holding capacity of gels which was attributed to the influence of the strongly hydrated calcium ions that interacted with the non-charged regions of proteins via site-specific interactions. PMID- 26869118 TI - Ayurvedic patients in Germany. AB - In the sociology of health and illness, the heterogeneous field of heterodox medicine is often conceptualised as a more or less homogeneous entity. All kinds of heterodox modes of treatment are pooled together in order to discover the heterodox patient. In this way, differences between several heterodox modes of treatment are lost and the emerging picture remains vague. In this paper, we concentrate on one particular mode of treatment: Ayurveda. Based on 14 semi structured interviews conducted with the patients of German Ayurvedic physicians, we examine the paths that lead patients to this form of Asian medicine, and how they process Ayurvedic concepts and make sense of them. It will be a story of how trust in heterodox medicine is built and confirmed, a story of how foreign knowledge is creatively received, modified and thus glocalised. We will also explore the patients' perception of their relationships with their physicians, for the success of heterodox medicine is often traced to a more satisfying, personal relationship with the physician when compared to the rather brief and technical consultations common in biomedicine. Finally, it is argued that Ayurvedic patients do not readily fit the notion that heterodox patients are active consumers. PMID- 26869119 TI - Shiatsu in Britain and Japan: Personhood, holism and embodied aesthetics. AB - In this paper, globalisation processes are examined through the prism of shiatsu, an originally Japanese, touch-based therapy, now practised in Europe, Japan, North America, and many other places. Examining this emergent plane of therapeutic practice provides an opportunity to reflect on categories of personhood, notably that of the individual, and its place within processes of globalisation. The article is divided into two parts. In the first part the holisms inherent to East Asian medical practice and underlying notions of personhood in Japan and Britain are critically examined. The seemingly reductionistic practice of 'bodily holism' in Japan is shown to reflect socio centred notions of the person. The concept of holism animating shiatsu in a British school in London, far from being Japanese, 'ancient', or 'timeless', is shown to reflect individualism characteristic of the New Age movement. In the second part of the paper, using an auto-phenomenological approach, a description of practitioner (my own) and client's lived experience of shiatsu is given in case study form. This illustrates how 'holism' is felt within the context of a shiatsu treatment. The aesthetic form of the shiatsu touch described is shown to be implicitly individualising. This has, it is argued, profound implications for understanding the embodied dimensions of practitioner-patient encounters, the potential efficacy of treatment, and more generally the practice of globalised East Asian 'holistic' therapies in Britain and other settings. PMID- 26869120 TI - Buddhism, science, and market: The globalisation of Tibetan medicine. AB - In this paper I discuss the processes by which Tibetan medicine has become globalised, and the ways in which these have come to determine, constrain, and, ultimately, transform local practices of healing in both Tibet and the West. I examine the degree to which globalisation, in particular international market capitalism, operating in this case through the Chinese state, structures the content of primary medical resources, confers legitimacy to certain technologies, and sets the ground rules by which the healers in charge of deploying such technologies are set into conversation with one another. I also argue that the cultural dimensions of globalisation enter the local context through the multiple stranded flows of people, images, and ideas, and contribute to redefinitions of identity, suffering, and body praxis among patients/consumers in diverse local contexts. I proceed within two registers of analysis. In the first, I analyse these movements in the context of Tibetan medicine as it has been transformed, practised, and used, in the Tibet Autonomous Region of China. In the second, the analytic lens shifts to a focus on Tibetan medicine as a 'global' alternative medicine in North America and Europe. The focus throughout is on the global-local dialectic: how Tibetan medicine is both produced as global commodity and consumed as 'local' tradition. PMID- 26869121 TI - "The medicine from China has rapid effects": Chinese medicine patients in Tanzania. AB - Traditional Chinese Medicine (TCM) involves both biomedical and traditional medical training, which makes well-trained TCM doctors inexpensive health care providers for primary health care. The Tanzanian Ministry of Health and Ministry of Commerce recognised this potential, and in the mid-1990s issued short-term licences for private TCM enterprises. In Dar es Salaam, some of these practices experienced a period of considerable growth, but by the year 2000 a degree of ambivalence if not resentment existed against Chinese medical doctors who were accused of unlawfully using biomedical medication, and the government refused to issue further licences. In addition, some 'doctors' had insufficient training or minimal clinical experience (though I also met some notable exceptions). This article asks why Tanzanian patients turn to the Chinese for medical treatment, and what patients know about Chinese medicine and medication. One of the chief findings is that the Swahili term dawa ya Kichina is vague, which allows patients to transfer their positive experiences with Chinese biomedical doctors during the period of socialist orientation onto the current, entrepreneurial TCM doctors. Dawa ya Kichina is often considered a rapidly effective 'advanced' 'traditional' medicine; its ready-made patent formulas, which make it look 'scientific' and 'modern', are easy to consume; and its entrepreneurial set-up has several advantages over the bureaucratic structures of 'hospital medicine'. Chinese anti malarials, artesiminin derivatives, reduce malarial fevers within hours, and though, strictly speaking, they are biomedical drugs, they are indeed dawa ya Kichina . Moreover, patients of TCM doctors sometimes experience rapid recovery, mostly due to skilled integration of biomedical and Chinese medical treatment. Further research is recommended to investigate the primary health care potential of such integrated Chinese and biomedical treatment. PMID- 26869122 TI - Korean medicine in Kazakhstan: Ideas, practices and patients. AB - Since the 1990s, after gaining independence by the Republic of Kazakhstan, various complementary therapies have grown rapidly there. Korean medicine in its several forms belongs among them. There is an important population of Korean deportees from Stalinist times, but this paper will show that the various forms of Korean medicine practised in Almaty, Kazakhstan's former capital, do not primarily cater for ethnic Koreans. Rather, as the paper demonstrates, it is important to see that there are different forms of Korean medicine attractive to clientele from different strata of society. Thus, there are, apart from the most traditional treatment practised at the Korean-Kazakhstani clinic in Almaty, two other newly invented modifications of Korean medicine: soo-jok and soo-ji . The paper embeds Korean medicine into the context of the drastic deterioration of the state health care system and general dissatisfaction with its services, on the one hand, and a generally supportive attitude of government authorities to complementary medicine, on the other. My empirical data suggest that in Kazakhstan people of different ethnic background, sex, age and education choose complementary therapies. The growing popularity of these therapies is not only attributed to public confidence in the methods that are perceived as 'traditional' but more importantly to the extremely difficult economic conditions which have made people search for cheaper treatment. The paper presents data that are critical of a purely culturalist interpretation of explaining the arrival of Korean medicine in Kazakhstan and suggests that it is the political economy of Korean medicine as a non-costly therapy which has made it attractive to a wide range of clients. PMID- 26869123 TI - Healing efficacy and the construction of charisma: A family's journey through the multiple medical field in Russia. AB - In the varieties of non-biomedical healing in Russia, the efficacy of treatment is based on the patient's recognition of the healer's charismatic legitimacy that translates directly into the power to change the lived reality of the ailing body. This paper considers charismatic healing power as emerging in the dyadic relationship between a healer and a patient, and analyses aesthetic and social elements of the charismatic bond between healer and patient. The paper is based on the ethnography of the multiple medical field in contemporary Russia, reflected in the narrative of a family's encounters with its various representatives in search for treatment alternatives for an incurable chronic disease. The acceptance of a healer's charisma is shown to build on an immediate embodied experience, but it is also suggested that this experience cannot be understood if divorced from its social diacritics. PMID- 26869127 TI - Legal Blindness From Severe Optic Nerve Head Drusen. PMID- 26869128 TI - Ocular Surface Squamous Neoplasia. PMID- 26869130 TI - Glaucoma Tube Changes After Suture Lysis Assessed by High-Resolution Anterior Segment Optical Coherence Tomography. PMID- 26869129 TI - Two-Year Follow-up of a Prepapillary Vascular Loop-Related Branch Retinal Artery Occlusion. PMID- 26869131 TI - The Suspected Macrosomic Fetus at Term: A Clinical Dilemma. AB - Estimation of fetal weight is an important component of antenatal and intrapartum management of pregnant women. While many clinicians use ultrasound estimates of fetal weight to assess fetal growth, there are inherent challenges in both the diagnosis and management of suspected fetal macrosomia. Given the inaccuracy in estimating fetal weight, and the risks that accompany cesarean birth or induction of labor, the management of suspected fetal macrosomia requires open communication and shared decision making between the woman and her health care providers. This case study and literature review highlight the current management and recommendations for suspected fetal macrosomia. PMID- 26869135 TI - Association of Compliance With Process-Related Quality Metrics and Improved Survival in Oral Cavity Squamous Cell Carcinoma. AB - IMPORTANCE: Quality metrics for patients with head and neck cancer are available, but it is unknown whether compliance with these metrics is associated with improved patient survival. OBJECTIVE: To identify whether compliance with various process-related quality metrics is associated with improved survival in patients with oral cavity squamous cell carcinoma who receive definitive surgery with or without adjuvant therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at a tertiary academic medical center among 192 patients with previously untreated oral cavity squamous cell carcinoma who underwent definitive surgery with or without adjuvant therapy between January 1, 2003, and December 31, 2010. Data analysis was performed from January 26 to August 7, 2015. INTERVENTIONS: Surgery with or without adjuvant therapy. MAIN OUTCOMES AND MEASURES: Compliance with a collection of process-related quality metrics possessing face validity that covered pretreatment evaluation, treatment, and posttreatment surveillance was evaluated. Association between compliance with these quality metrics and overall survival, disease-specific survival, and disease-free survival was calculated using univariable and multivariable Cox proportional hazards analysis. RESULTS: Among 192 patients, compliance with the individual quality metrics ranged from 19.7% to 93.6% (median, 82.8%). No pretreatment or surveillance metrics were associated with improved survival. Compliance with the following treatment-related quality metrics was associated with improved survival: elective neck dissection with lymph node yield of 18 or more, no unplanned surgery within 14 days of the index surgery, no unplanned 30 day readmissions, and referral for adjuvant radiotherapy for pathologic stage III or IV disease. Increased compliance with a "clinical care signature" composed of these 4 metrics was associated with improved overall survival, disease-specific survival, and disease-free survival on univariable analysis (log-rank test; P < .05 for each). On multivariable analysis controlling for pT stage, pN stage, extracapsular spread, margin status, and comorbidity, increased compliance with these 4 metrics was associated with improved overall survival (100% vs <=50% compliance: adjusted hazard ratio [aHR], 4.2; 95% CI, 2.1-8.5; 100% vs 51%-99% compliance: aHR, 1.7; 95% CI, 1.0-3.1), improved disease-specific survival (100% vs <=50% compliance: aHR, 3.9; 95% CI, 1.7-9.0; 100% vs 51%-99%: aHR, 1.3; 95% CI, 0.6-2.9), and improved disease-free survival (100% vs <=50% compliance: aHR, 3.0; 95% CI, 1.5-5.8; 100% vs 51%-99% compliance: aHR, 1.6; 95% CI, 0.9-2.7). CONCLUSIONS AND RELEVANCE: Compliance with a core set of process-related quality metrics was associated with improved survival for patients with surgically managed oral cavity squamous cell carcinoma. Multi-institutional validation of these metrics is warranted. PMID- 26869136 TI - Expression of holo-proteorhodopsin in Synechocystis sp. PCC 6803. AB - Retinal-based photosynthesis may contribute to the free energy conversion needed for growth of an organism carrying out oxygenic photosynthesis, like a cyanobacterium. After optimization, this may even enhance the overall efficiency of phototrophic growth of such organisms in sustainability applications. As a first step towards this, we here report on functional expression of the archetype proteorhodopsin in Synechocystis sp. PCC 6803. Upon use of the moderate-strength psbA2 promoter, holo-proteorhodopsin is expressed in this cyanobacterium, at a level of up to 10(5) molecules per cell, presumably in a hexameric quaternary structure, and with approximately equal distribution (on a protein-content basis) over the thylakoid and the cytoplasmic membrane fraction. These results also demonstrate that Synechocystis sp. PCC 6803 has the capacity to synthesize all trans-retinal. Expressing a substantial amount of a heterologous opsin membrane protein causes a substantial growth retardation Synechocystis, as is clear from a strain expressing PROPS, a non-pumping mutant derivative of proteorhodopsin. Relative to this latter strain, proteorhodopsin expression, however, measurably stimulates its growth. PMID- 26869138 TI - [Cardiovascular screening prior to sport practice in children and adolescents]. PMID- 26869137 TI - Development of a Decision Aid for Cardiopulmonary Resuscitation Involving Intensive Care Unit Patients' and Health Professionals' Participation Using User Centered Design and a Wiki Platform for Rapid Prototyping: A Research Protocol. AB - BACKGROUND: Cardiopulmonary resuscitation (CPR) is an intervention used in cases of cardiac arrest to revive patients whose heart has stopped. Because cardiac arrest can have potentially devastating outcomes such as severe neurological deficits even if CPR is performed, patients must be involved in determining in advance if they want CPR in the case of an unexpected arrest. Shared decision making (SDM) facilitates discussions about goals of care regarding CPR in intensive care units (ICUs). Patient decision aids (DAs) are proven to support the implementation of SDM. Many patient DAs about CPR exist, but they are not universally implemented in ICUs in part due to lack of context and cultural adaptation. Adaptation to local context is an important phase of implementing any type of knowledge tool such as patient DAs. User-centered design supported by a wiki platform to perform rapid prototyping has previously been successful in creating knowledge tools adapted to the needs of patients and health professionals (eg, asthma action plans). This project aims to explore how user centered design and a wiki platform can support the adaptation of an existing DA for CPR to the local context. OBJECTIVE: The primary objective is to use an existing DA about CPR to create a wiki-based DA that is adapted to the context of a single ICU and tailorable to individual patient's risk factors while employing user-centered design. The secondary objective is to document the use of a wiki platform for the adaptation of patient DAs. METHODS: This study will be conducted in a mixed surgical and medical ICU at Hotel-Dieu de Levis, Quebec, Canada. We plan to involve all 5 intensivists and recruit at least 20 alert and oriented patients admitted to the ICU and their family members if available. In the first phase of this study, we will observe 3 weeks of daily interactions between patients, families, intensivists, and other allied health professionals. We will specifically observe 5 dyads of attending intensivists and alert and oriented patients discussing goals of care concerning CPR to understand how a patient DA could support this decision. We will also conduct individual interviews with the 5 intensivists to identify their needs concerning the implementation of a DA. In the second phase of the study, we will build a first prototype based on the needs identified in Phase I. We will start by translating an existing DA entitled "Cardiopulmonary resuscitation: a decision aid for patients and their families." We will then adapt this tool to the needs we identified in Phase I and archive this first prototype in a wiki. Building on the wiki's programming architecture, we intend to integrate the Good Outcome Following Attempted Resuscitation risk calculator into our DA to determine personal risks and benefits of CPR for each patient. We will then present the first prototype to 5 new patient-intensivist dyads. Feedback about content and visual presentation will be collected from the intensivists through short interviews while longer interviews will be conducted with patients and their family members to inform the visual design and content of the next prototype. After each rapid prototyping cycle, 2 researchers will perform qualitative content analysis of data collected through interviews and direct observations. We will attempt to solve all content and visual design issues identified before moving to the next round of prototyping. In all, we will conduct 3 prototyping cycles with a total of 15 patient-intensivist dyads. RESULTS: We expect to develop a multimedia wiki-based DA to support goals of care discussions about CPR adapted to the local needs of patients, their family members, and intensivists and tailorable to individual patient risk factors. The final version of the DA as well as the development process will be housed in an open-access wiki and free to be adapted and used in other contexts. CONCLUSIONS: This study will shed new light on the development of DAs adapted to local context and tailorable to individual patient risk factors employing user-centered design and a wiki to support rapid prototyping of content and visual design issues. PMID- 26869139 TI - [Renal artery dissection after abdominal injury]. PMID- 26869140 TI - [Prolactinomas in a paediatric population]. PMID- 26869141 TI - [Epidemiology and risk factors in injuries due to fall in infants under one year old]. AB - OBJECTIVES: To describe the epidemiological characteristics of unintentional injuries due to falls in children under one year and to analyse the risk factors associated with severe injuries. PATIENTS AND METHODS: This multicentre, observational and cross-sectional study included all children less than one year treated for unintentional fall in the Emergency Departments of 8 Spanish Hospitals, belonging to the "Unintentional Paediatric Injury Workshop" of the Spanish Paediatric Emergency Society, between March 1st, 2014 and February 28th, 2015. RESULTS: Out of 289,887 emergency department cases, 1,022 were due to unintentional falls. The median age was 8 months and 52.5% were males. Fall injuries were more frequent among children aged 9-12 months (37.6%), and 83.5% occurred at home. The most common mechanism was fall from nursery equipment (69.4%), and 47.8% occurred from a height under 50cm. More than two-thirds (68%) of falls were witnessed, but in half of the cases (329) the caregiver was not in area. Serious injuries were seen in 12% of cases. In this study, a fall height greater than 50cm, falls in the street, from the arms of the carer, and from the stairs were identified as independent risk factors for worse outcomes. CONCLUSIONS: The most serious injuries occur in children <3 months and from a height of >50cm, though not related to unwitnessed falls. Because the most common serious injury mechanism is the fall from the arms of the carer, from stairs, and falls in the street, these facts should be highlighted in order to avoid morbidity. PMID- 26869142 TI - Oceanobacillus halophilus sp. nov., a novel moderately halophilic bacterium from a hypersaline lake. AB - A moderately halophilic bacterium was isolated from a brine sample of a hypersaline lake, Aran-Bidgol, in Iran. The strain, designated J8BT, was Gram stain-positive, endospore-forming, rod-shaped, strictly aerobic, motile and produced cream colonies. Strain J8BT grew in NaCl at between 3.0-15.0 % (w/v) (optimally at 7.5 % NaCl, w/v), between pH 6.5-9.0 (optimally at pH 8.0) and between 20-45 degrees C (optimally at 35 degrees C). Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that strain J8BT is a member of the genus Oceanobacillus and most closely related to Oceanobacillus profundus CL MP28T, Oceanobacillus polygoni SA9T and Oceanobacillus oncorhynchi R-2T (96.9 %, 96.3 % and 96.2 % similarities, respectively). The level of DNA-DNA relatedness between the novel isolate and O. profundus IBRC-M 10567T was 10 %. The major cellular fatty acids of the isolate were anteiso-C15 : 0, iso-C15 : 0 and anteiso C17 : 0. The polar lipid pattern of strain J8BT consisted of phosphatidylglycerol, diphosphatidylglycerol, five phospholipids, two aminolipids and two glycoaminolipids. It contained MK-7 as the predominant menaquinone and meso-diaminopimelic acid in the cell-wall peptidoglycan. The G+C content of the genomic DNA of this strain was 39.2 mol%. Phenotypic characteristics, phylogenetic analysis and DNA-DNA relatedness data suggest that this strain represents a novel species of the genus Oceanobacillus, for which the name Oceanobacillus halophilus sp. nov. is proposed. The type strain is strain J8BT ( = IBRC-M 10444T = DSM 23996T). PMID- 26869145 TI - Novel Radiofrequency-Assisted Thermal Processing Improves the Gelling Properties of Standard Egg White Powder. AB - Effect of radiofrequency (RF)-assisted thermal processing on quality and functional properties of high-foaming standard egg white powder (std. EWP, pH approximately 7.0) was investigated and compared with traditional processing (heat treatment in a hot room at 58 degrees C for at least 14 d). The RF assisted thermal treatments were selected to meet the pasteurization requirements and to improve the functional properties of the std. EWP. The treatment conditions were: RF heating to 60, 70, 80, and 90 degrees C followed by holding in a hot air oven at those temperatures for different periods ranging from 4 h at 90 degrees C to 72 h at 60 degrees C. The quality (color and solubility) and functional properties (foaming properties: foaming capacity and foam stability; and gelling properties: water holding capacity and gel-firmness) of the std. EWP were investigated. RF-assisted thermal processing did not affect the color and solubility of std. EWP at any of the treatment conditions. In general, the foaming and gelling properties of RF-assisted thermally processed std. EWP increased with an increase in temperature and treatment duration. The optimal RF assisted treatment conditions to produce std. EWP with similar functional properties as the traditionally processed (hot room processed) std. EWP were 90 degrees C for >=8 h. These optimal conditions were similar to those for high gel egg white powder (HG-EWP, pH approximately 9.5). The RF-assisted thermal pasteurization improved the gelling properties of std. EWP to the levels of HG EWP, leading to newer applications of this functionally improved safe product. The RF-assisted thermal processing allows the processor to produce a HG-EWP from std. EWP subsequent to processing while simultaneously pasteurizing the product, thus assuring the product safety. PMID- 26869144 TI - Factors associated with telemonitoring use among patients with chronic heart failure. AB - Background In adults with chronic heart failure (HF; defined as people with previously diagnosed left ventricular dysfunction) telemonitoring randomized controlled trials (RCTs) failed to consistently demonstrate improved clinical outcomes. We aimed to examine if patient and HF characteristics are associated with device preferences and use. Methods Using a cross-sectional, multicenter, international design, ambulatory and hospitalized adults with HF in Ohio, California, and Denmark viewed a six-minute video of telemonitoring configurations (tablet, smart phone, and key fob) and completed questionnaires. Comparative analyses were performed and when significant, pairwise comparisons were performed using Bonferroni-adjusted significance levels. Results Of 206 participants, 48.2% preferred smart phones for telemonitoring, especially when traveling (54.8%), with new/worsening symptoms (50%), for everyday use (50%), and connecting with doctors (48.5%). Participants preferred two-way communication and a screen with words over voice or number pads. Of device purposes, allowing for nurse communication ranked highest, followed by maintaining overall health. Very few patient and HF factors were associated with device preferences. Patients with higher health literacy ( p = 0.007), previous/current device use history ( p = 0.008), higher education level ( p = 0.035), and married/cohabitating status ( p = 0.023) had higher perceptions of ease of using devices. Those who were asymptomatic or had mild HF had higher self-confidence for health devices ( p = 0.024) and non-white patients perceived devices as more useful ( p = 0.033). Conclusion Telemonitoring use may be enhanced by simple plug-and-play type devices, two-way communication, and features that meet patients' personal learning and use needs. PMID- 26869143 TI - Engineering a Carbohydrate-processing Transglycosidase into Glycosyltransferase for Natural Product Glycodiversification. AB - Glycodiversification broadens the scope of natural product-derived drug discovery. The acceptor substrate promiscuity of glucosyltransferase-D (GTF-D), a carbohydrate-processing enzyme from Streptococcus mutans, was expanded by protein engineering. Mutants in a site-saturation mutagenesis library were screened on the fluorescent substrate 4-methylumbelliferone to identify derivatives with improved transglycosylation efficiency. In comparison to the wild-type GTF-D enzyme, mutant M4 exhibited increased transglycosylation capabilities on flavonoid substrates including catechin, genistein, daidzein and silybin, using the glucosyl donor sucrose. This study demonstrated the feasibility of developing natural product glycosyltransferases by engineering transglycosidases that use donor substrates cheaper than NDP-sugars, and gave rise to a series of alpha glucosylated natural products that are novel to the natural product reservoir. The solubility of the alpha-glucoside of genistein and the anti-oxidant capability of the alpha-glucoside of catechin were also studied. PMID- 26869147 TI - Electronic structures of greigite (Fe3S4): A hybrid functional study and prediction for a Verwey transition. AB - Greigite (Fe3S4) is a ferrimagnetic mineral with vital functions in both the bio geochemical cycle and novel technological applications. However, the ground state electronic structure of this material has not been fully characterized by either experiment or theory. In the present study, ab initio calculations using the hybrid functional method have been performed to investigate the electronic structure and magnetic properties. It is found that the cubic structure observed under ambient temperature is a half metal and is metastable. A more stable monoclinic structure slightly distorted from the cubic form is found. The structural distortion is induced by charge ordering and associated with a metal to-insulator transition, resulting in a semiconductive ground state with a bandgap of ~0.8 eV and a magnetic moment of 4 MUB per formula unit. The results predict, similar to the magnetite (Fe3O4), a Verwey transition may exist in greigite, although it has not yet been observed experimentally. PMID- 26869146 TI - Energetics of Table Tennis and Table Tennis-Specific Exercise Testing. AB - PURPOSE: To test the hypotheses that the metabolic profile of table tennis is dominantly aerobic, anaerobic energy is related to the accumulated duration and intensity of rallies, and activity and metabolic profile are interrelated with the individual fitness profile determined via table tennis-specific tests. METHODS: Eleven male experienced table tennis players (22 +/- 3 y, 77.6 +/- 18.9 kg, 177.1 +/- 8.1 cm) underwent 2 simulated table tennis matches to analyze aerobic (WOXID) energy, anaerobic glycolytic (WBLC) energy, and phosphocreatine breakdown (WPCr); a table tennis-specific graded exercise test to measure ventilatory threshold and peak oxygen uptake; and an exhaustive supramaximal table tennis effort to determine maximal accumulated deficit of oxygen. RESULTS: WOXID, WBLC, and WPCr corresponded to 96.5% +/- 1.7%, 1.0% +/- 0.7%, and 2.5% +/- 1.4%, respectively. WOXID was interrelated with rally duration (r = .81) and number of shots per rally (r = .77), whereas match intensity was correlated with WPCr (r = .62) and maximal accumulated oxygen deficit (r = .58). CONCLUSIONS: The metabolic profile of table tennis is predominantly aerobic and interrelated with the individual fitness profile determined via table tennis-specific tests. Table tennis-specific ventilatory threshold determines the average oxygen uptake and overall WOXID, whereas table tennis-specific maximal accumulated oxygen deficit indicates the ability to use and sustain slightly higher blood lactate concentration and WBLC during the match. PMID- 26869148 TI - Acute effects of theanine, caffeine and theanine-caffeine combination on attention. AB - OBJECTIVE: l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. DESIGN: In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. RESULTS: Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine * caffeine interaction was observed for RVRT or N2-P300 amplitude. DISCUSSION: A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses. PMID- 26869149 TI - Piracetam for reducing the incidence of painful sickle cell disease crises. AB - BACKGROUND: Sickle cell disease is one of the most common genetic disorders. Sickle cell crises in which irregular and dehydrated cells contribute to blocking of blood vessels are characterised by episodes of pain. Treatment is mainly supportive and symptomatic. In vitro studies with piracetam indicate that it has the potential for inhibition and a reversal of the process of sickling of erythrocytes. This is an update of a previously published Cochrane review. OBJECTIVES: To assess the effectiveness of piracetam for reducing the incidence of painful sickle cell disease crises. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Last search of the Group's Haemoglobinopathies Trials Register: 21 September 2015. SELECTION CRITERIA: Randomised controlled trials comparing orally administered piracetam to placebo or standard care in people, of all ages and both sexes, with sickle cell disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Trial authors were contacted for additional information. Adverse effects data were collected from the trials. MAIN RESULTS: Three trials involving 169 participants were included in the review. A limited amount of data addressing some of the primary and some of the secondary outcomes were provided, but data were incomplete and based on un validated assumptions used in the evaluation of outcomes. One trial reported a reduction in the number of pain crises and their severity with active intervention than placebo but presented no data to confirm these results. A second trial presented a monthly global pain score based on the number of sickle cell crises and severity of pain but included no separate data for these primary outcomes. Although there was no significant difference between the piracetam and placebo periods for the number of days of hospitalisation (P = 0.87) in one trial, inconsistencies in the criteria necessary for hospitalisation during sickle crises did not permit accurate conclusions to be drawn. Two of the trials reported participant satisfaction with piracetam but provided no details as to how this satisfaction had been assessed. There were no reports of toxicity or adverse effects with piracetam other than one participant who experienced dizziness. AUTHORS' CONCLUSIONS: The small number of included trials and their poor methodological quality provided insufficient reliable evidence to support the routine use of this medication for preventing the incidence of painful sickle cell disease crises.We will continue to run searches to identify any potentially relevant trials; however, we do not plan to update other sections of the review until new trials are published. PMID- 26869150 TI - Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases. AB - According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases. PMID- 26869151 TI - Chronic Kidney Disease in Aged Cats: Clinical Features, Morphology, and Proposed Pathogeneses. AB - Chronic kidney disease (CKD) is the most common metabolic disease of domesticated cats, with most affected cats being geriatric (>12 years of age). The prevalence of CKD in cats exceeds that observed in dogs, and the frequency of the diagnosis of CKD in cats has increased in recent decades. Typical histologic features include interstitial inflammation, tubular atrophy, and fibrosis with secondary glomerulosclerosis. In contrast to people and dogs, primary glomerulopathies with marked proteinuria are remarkably rare findings in cats. Although a variety of primary renal diseases have been implicated, the disease is idiopathic in most cats. Tubulointerstitial changes, including fibrosis, are present in the early stages of feline CKD and become more severe in advanced disease. A variety of factors-including aging, ischemia, comorbid conditions, phosphorus overload, and routine vaccinations-have been implicated as factors that could contribute to the initiation of this disease in affected cats. Factors that are related to progression of established CKD, which occurs in some but not all cats, include dietary phosphorus intake, magnitude of proteinuria, and anemia. Renal fibrosis, a common histologic feature of aged feline kidneys, interferes with the normal relationship between peritubular capillaries and renal tubules. Experimentally, renal ischemia results in morphologic changes similar to those observed in spontaneous CKD. Renal hypoxia, perhaps episodic, may play a role in the initiation and progression of this disease. PMID- 26869152 TI - Age-Related Changes in Skeletal Muscle of Cattle. AB - Sarcopenia, the age-related loss of muscle mass and strength, is a multifactorial condition that represents a major healthcare concern for the elderly population. Although its morphologic features have been extensively studied in humans, animal models, and domestic and wild animals, only a few reports about spontaneous sarcopenia exist in other long-lived animals. In this work, muscle samples from 60 healthy Podolica-breed old cows (aged 15-23 years) were examined and compared with muscle samples from 10 young cows (3-6 years old). Frozen sections were studied through standard histologic and histoenzymatic procedures, as well as by immunohistochemistry, immunofluorescence, and Western blot analysis. The most prominent age-related myopathic features seen in the studied material included angular fiber atrophy (90% of cases), mitochondrial alterations (ragged red fibers, 70%; COX-negative fibers, 60%), presence of vacuolated fibers (75%), lymphocytic (predominantly CD8+) inflammation (40%), and type II selective fiber atrophy (40%). Immunohistochemistry revealed increased expression of major histocompatibility complex I in 36 cases (60%) and sarcoplasmic accumulations of beta-amyloid precursor protein-positive material in 18 cases (30%). In aged cows, muscle atrophy was associated with accumulation of myostatin. Western blot analysis indicated increased amount of both proteins-myostatin and beta-amyloid precursor protein-in muscles of aged animals compared with controls. These findings confirm the presence of age-related morphologic changes in cows similar to human sarcopenia and underline the possible role of amyloid deposition and subsequent inflammation in muscle senescence. PMID- 26869154 TI - A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) was initially isolated from a Saudi Arabian man with fatal pneumonia. Since the original case in 2012, MERS-CoV infections have been reported in >1500 humans, and the case fatality rate is currently 35%. This lineage C betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. Although the clinical presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV. PMID- 26869155 TI - Interaction of the ionic liquid [BMP][TFSA] with rutile TiO2(110) and coadsorbed lithium. AB - Aiming at a fundamental understanding of the processes at the electrode|ionic liquid interface in Li ion batteries, we investigated the interaction of the ionic liquid n-butyl-n-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [BMP][TFSA] and of Li with a reduced rutile TiO2(110) (1 * 1) surface as well as the interaction between [BMP][TFSA] and Li on the TiO2(110) surface under ultrahigh vacuum (UHV) conditions by X-ray photoelectron spectroscopy and scanning tunnelling microscopy. Between 80 K and 340 K [BMP][TFSA] adsorbs molecularly on the surface and at higher temperatures decomposition is observed, resulting in products such as Sad, Fad and TiNx. The decomposition pattern is compared to proposals based on theory. Small amounts of Li intercalate even at 80 K into TiO2(110), forming Li(+) and Ti(3+) species. The stoichiometry in the near surface region corresponds to Li7Ti5O12. For higher coverages in the range of several monolayers part of the Li remains on the surface, forming a Li2O cover layer. At 300 K, Ti(3+) species become sufficiently mobile to diffuse into the bulk. Li post-deposition on a [BMP][TFSA] covered TiO2(110) surface at 80 K results in two competing reactions, Li intercalation and reaction with the IL, resulting in the decomposition of the IL. Upon warming up, the Ti(3+) formed at low T is consumed by reaction with the IL adlayer and intermediate decomposition products. Post-deposition of [BMP][TFSA] (300 K) on a surface pre-covered with a Li2O/Li7Ti5O12 layer results in the partial reaction of [BMP][TFSA] with the Li(+) and Ti(3+) species, which gets completed at higher temperatures. PMID- 26869157 TI - Reply to 'Comment on: Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizmab'. PMID- 26869156 TI - Neuroretinal alterations in the early stages of diabetic retinopathy in patients with type 2 diabetes mellitus. AB - PurposeTo study neuroretinal alterations in patients affected by type 2 diabetes with no diabetic retinopathy (DR) or mild nonproliferative diabetic retinopathy (NPDR) and without any sign of diabetic macular edema.Patients and methodsIn total, 150 type 2 diabetic patients with no (131 eyes) or mild NPDR (19 eyes) and 50 healthy controls were enrolled in our study. All underwent a complete ophthalmologic examination, including Spectral-Domain optical coherence tomography (SD-OCT). Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thickness values were calculated after automated segmentation of SD-OCT scans.ResultsMean best-corrected visual acuity was 0.0+/ 0.0 LogMAR in all the groups. Mean GC-IPL thickness was 80.6+/-8.1 MUm in diabetic patients and 85.3+/-9.9 MUm in healthy controls, respectively (P=0.001). Moreover, evaluating the two different diabetic groups, GC-IPL thickness was 80.7+/-8.1 MUm and 79.7+/-8.8 MUm in no-DR and mild-NPDR group (P=0.001 and P=0.022 compared with healthy controls, respectively). Average RNFL thickness was 86.1+/-10.1 MUm in diabetes patients and 91.2+/-7.3 MUm in controls, respectively (P=0.003). RNFL thickness was 86.4+/-10.2 MUm in no-DR group and 84.1+/-9.4 MUm in mild-NPDR group (P=0.007 and P=0.017 compared with healthy controls, respectively).ConclusionWe demonstrated a significantly reduced GC-IPL and RNFL thickness values in both no-DR and mild-NPDR groups compared with healthy controls. These data confirmed neuroretinal alterations are early in diabetes, preceding microvascular damages. PMID- 26869158 TI - Anterior lamellar recession, blepharoplasty, and supratarsal fixation for cicatricial upper eyelid entropion without lagophthalmos. AB - PURPOSE: To assess the results of anterior lamellar recession, blepharoplasty, and supratarsal fixation procedure in patients with upper eyelid cicatricial entropion without lagophthalmos. METHODS: In a prospective interventional case series, 52 eyelids (32 patients) were included (April 2009-December 2010). Excluded were patients with previous eyelid surgeries, lagophthalmos, and <12 months of follow-up. Using a microscope, after recessing anterior lamella 3-4 mm above the eyelid margin, it was fixed with 4-5 interrupted 6-0 vicryl sutures. Excess anterior lamella was then excised (blepharoplasty), supratarsal fixation sutures (6-0 vicryl) were put and the skin was closed with 6-0 nylon sutures. Success and failure defined based upon eyelash-globe touch on the last follow-up visit (at least 12 months), respectively. RESULTS: There were 21 females (65.6%) and 11 males (34.4%) with a mean age of 69.7 years (SD=6.9) and mean follow-up of 21.06 months (SD=8.26). Success was observed in 39 (75%) and failure in 13 (25%). Mean time of failure was 4.5 months (SD=3). Although re-treatment with radio frequency electrolysis (eight eyelids) and re-anterior lamellar recession (two eyelids) resulted in success in 12 eyelids with failure, two patients (three eyelids) declined further procedure. Except for thickened eyelid margin, no complications were observed. CONCLUSION: Anterior lamellar recession, blepharoplasty, and supratarsal fixation procedure is an effective and safe technique for the treatment of the upper eyelid cicatricial entropion without lagophthalmos. PMID- 26869153 TI - Contributions of Nonhuman Primates to Research on Aging. AB - Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID- 26869159 TI - Involution patterns of retinopathy of prematurity after treatment with intravitreal bevacizumab: implications for follow-up. AB - PURPOSE: To describe involution patterns following monotherapy with intravitreal bevacizumab injection (IVB) for type 1 retinopathy of prematurity (ROP) in zone I or zone II posterior. METHODS: A retrospective chart review of infants treated with IVB from January 2010-April 2014. Infants with minimum of 82 weeks postmenstrual age at last follow-up were included. Primary outcome was timing of involution of type 1 ROP for the first 12 weeks post treatment. Secondary outcomes were development of any recurrence and structural outcome at last follow up. Retinal examination records, fundus, and flourescein angiography images were reviewed. RESULTS: Twenty-eight eyes were included. Average follow-up post treatment was 33.9+/-9.7 months (range 21.4-61.9). Cumulative frequency of regression of plus disease was seen in 73.3, 86.7, and 100% of eyes by days 3, 5, and 8, respectively. Regression of both stage 3 and plus disease was observed in 29, 82, 88, and 100% by weeks 1, 2, 3, and 4, respectively. Within the first 3 months, 17/28 eyes developed recurrence to stage 1 or 2 after regression. None developed recurrence of plus disease. By the end of 3 months 18% of eyes vascularized into zone III. At a mean of 24+/-17.3 months, 39% of eyes were not vascularized into zone III as seen on flourescein angiography with scleral indentation. CONCLUSION: Our experience suggests regression of plus disease and stage 3 are expected within the first 4 weeks after bevacizumab treatment. Recurrence may occur despite initial regression and requires careful follow-up. PMID- 26869160 TI - Comment on: 'Intravitreal aflibercept for macular oedema secondary to central retinal vein occlusion in patients with prior treatment with bevacizumab or ranibizumab'. PMID- 26869161 TI - A prospective outcome study of membranous and solid distal common canalicular obstructions. AB - PURPOSE: To prospectively evaluate the surgical outcomes of membranous and solid distal common canalicular obstructions (CCOs) following endoscopic dacryocystorhinostomy (EnDCR) and lacrimal intubation combined with either membranotomy or trephination. METHODS: This was a prospective, non-randomized, consecutive interventional case series. Inclusion criteria included patients undergoing EnDCR with evidence of a membranous block or more solid obstruction of the distal common canaliculus, treated with membranotomy or canalicular trephination. Complete CCO was confirmed pre-operatively using dacryocystography and dacryoscintigraphy. All patients received bicanalicular intubation for 3 months with a minimum follow-up of 12 months. Functional and anatomical success was assessed at 4 weeks, 3 months, and 12 months following surgery. Functional success was defined as subjective improvement of epiphora and anatomical success as the presence of a patent ostium and a positive dye test on nasal endoscopy. RESULTS: Twenty-nine patients were included in the study with a mean age of 58 years. Twenty-one patients (72%) received a membranotomy and eight (28%) required trephination. At 12 months, the functional and anatomical success rate in the membranotomy group was 90% (19/21) and 100% (21/21), respectively, and in trephination group the functional and anatomical success rate was 63% (5/8). There were no intra-operative or lacrimal stent-related complications. CONCLUSIONS: Identifying and excising distal CCOs in association with EnDCR and lacrimal intubation is associated with a high degree of functional (83%) and anatomical (90%) success. The success of membranous obstructions appear be superior to outcomes for solid obstructions of the distal common canaliculus that require trephination. PMID- 26869162 TI - Post-traumatic endophthalmitis in 143 eyes of children and adolescents from India. AB - PURPOSE: The purpose of this study was to describe clinical features, risk factors, causative organisms, treatment options, and outcomes of post-traumatic endophthalmitis in children and adolescents. METHODS: Retrospective interventional case series. Case records of 143 consecutive eyes presenting with post-traumatic endophthalmitis between 1997 and 2007 were reviewed. Univariate and multivariate analysis were done to analyze factors associated with adverse outcomes. RESULTS: Mean age at presentation was 9.2 years (median 8 years, range: 2 months to 18 years). Broomstick and hypodermic needle were most common causes for injuries. Common presenting features were cataract (n=51), hypopyon (n=45) and retinal detachment (n=29). Corneal abscess (n=21; OR: 5, CI: 1.4-18.7) and retinal detachment (n=29, OR: 5, CI: 1.6-11.3) were independent risk factors for poor outcome (P=0.04 and 0.012, respectively). Gram-positive bacteria were isolated in 54% (n=31) of culture-positive cases. Forty-nine (34%) patients had ambulatory vision at final visit. Patients who received treatment within 24 h were 3.6 and 9 times more likely to have better anatomical outcome than those treated at 2-7 days, or >7 days, respectively (P=0.0001). Patients undergoing early vitrectomy were 27 times more likely to have better outcome (P=0.0001). CONCLUSION: Post-traumatic endophthalmitis in children is more common in boys <10 years of age and most often caused by injury with organic matter. Corneal abscess and retinal detachment are associated with poor outcome. E. fecalis is the most common causative organism. Early vitrectomy results in better outcomes. PMID- 26869164 TI - Physisorption of alpha-chymotrypsin on SiO2 and TiO2: A comparative study via experiments and molecular dynamics simulations. AB - In order to understand fundamental interactions at the interface between immobilized enzymes and ceramic supports, the authors compare the adsorption features of chymotrypsin on SiO2 and TiO2 colloidal particles by means of a combination of adsorption experiments and molecular dynamics simulations. While the dependency of the adsorption amount on pH is consistent with the trend predicted the Derjaguin-Landau-Verwey-Overbeek theory, other effects can only be rationalized if the atomic-scale details of the water-mediated protein-surface interactions are considered. On both surfaces, a clear driving force for the formation of a double monolayer at the saturation coverage is found. Although nearly equal free energies of adsorption are estimated on the two materials via a Langmuir adsorption analysis, about 50% more proteins per unit of surface can be accommodated on TiO2 than on SiO2. This is probably due to the lower surface diffusion mobility of the adsorbed protein in the latter case. Surface anchoring is realized by a combination of direct ionic interactions between charged proteins and surface sites (more pronounced for SiO2) and distinct structuring of the surface hydration layers in which the contact residues are embedded (more pronounced for TiO2). Finally, normalization of the data with respect to particle surface areas accessible to the proteins, rather than determined by means of the Brunauer-Emmett-Teller nitrogen adsorption isotherm, is crucial for a correct interpretation of the results. PMID- 26869163 TI - Central retinal vein occlusion: modifying current treatment protocols. AB - Central retinal vein occlusion (CRVO) is a common retinal vascular disorder that can result in severe visual acuity loss. The randomized control study, CRUISE, helped establish anti-VEGFs as the standard of care in cases with CRVO. The extension studies for CRUISE; HORIZON and RETAIN showed that not all visual gains are maintained beyond the first year. In addition, patients showed different behavior patterns; with some patients showing complete response with few recurrences, whereas others showed partial or even no response with multiple recurrences. Long-term follow-up demonstrated that patients responding poorly to anti-VEGFs tended to do so early in the course of treatment. It also demonstrated the effectiveness of a pro re nata (PRN) protocol for improving vision and maintaining these gains over long-term follow-ups. The SHORE study further illustrated this point by demonstrating that there were minimal differences in visual outcomes between patients receiving monthly injections and patients being treated PRN. In this review we analyzed the data from the major randomized clinical trials (RCT) that looked at anti-VEGFs as the primary treatment modality in patients with CRVO (CRUISE and the extension studies HORIZON and RETAIN for ranibizumab as well as GALILEO and COPERNICUS for aflibercept). In addition, we looked at SCORE and GENEVA to help determine whether there is a place for steroids as a first line therapy in current treatment practice. We then explored alternative treatment regimens such as laser therapy and switching between anti VEGF agents and/or steroids for non or partially responding patients. Finally, we propose a simplified modified treatment algorithm for patients with CRVO for better long-term outcomes in all types of responders. PMID- 26869165 TI - Inkjet deposition of itraconazole onto poly(glycolic acid) microneedle arrays. AB - Poly(glycolic acid) microneedle arrays were fabricated using a drawing lithography process; these arrays were modified with a drug release agent and an antifungal agent by piezoelectric inkjet printing. Coatings containing poly(methyl vinyl ether-co-maleic anhydride), a water-soluble drug release layer, and itraconazole (an antifungal agent), were applied to the microneedles by piezoelectric inkjet printing. Microscopic evaluation of the microneedles indicated that the modified microneedles contained the piezoelectric inkjet printing-deposited agents and that the surface coatings were released in porcine skin. Energy dispersive x-ray spectrometry aided in confirmation that the piezoelectric inkjet printing-deposited agents were successfully applied to the desired target areas of the microneedle surface. Fourier transform infrared spectroscopy was used to confirm the presence of the component materials in the piezoelectric inkjet printing-deposited material. Itraconazole-modified microneedle arrays incubated with agar plates containing Candida albicans cultures showed zones of growth inhibition. PMID- 26869166 TI - Acinetobacter plantarum sp. nov. isolated from wheat seedlings plant. AB - Strain THG-SQM11(T), a Gram-negative, aerobic, non-motile, coccus-shaped bacterium, was isolated from wheat seedlings plant in P. R. China. Strain THG SQM11(T) was closely related to members of the genus Acinetobacter and showed the highest 16S rRNA sequence similarities with Acinetobacter junii (97.9 %) and Acinetobacter kookii (96.1 %). DNA-DNA hybridization showed 41.3 +/- 2.4 % DNA reassociation with A. junii KCTC 12416(T). Chemotaxonomic data revealed that strain THG-SQM11(T) possesses ubiquinone-9 as the predominant respiratory quinone, C18:1 omega9c, summed feature 3 (C16:1 omega7c and/or C16:1 omega6c), and C16:0 as the major fatty acids. The major polar lipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylcholine. The DNA G+C content was 41.7 mol %. These data, together with phenotypic characterization, suggest that the isolate represents a novel species, for which the name Acinetobacter plantarum sp. nov. is proposed, with THG-SQM11(T) as the type strain (=CCTCC AB 2015123(T) =KCTC 42611(T)). PMID- 26869167 TI - Conditioned umbilical cord tissue provides a natural three-dimensional storage compartment as in vitro stem cell niche for human mesenchymal stroma/stem cells. AB - BACKGROUND: The use of large amounts of human multipotent mesenchymal stroma/stem cells (MSC) for cell therapies represents a desirable property in tissue engineering and banking in the field of regenerative medicine. METHODS AND RESULTS: Whereas cryo-storage of umbilical cord (UC) tissue pieces in liquid nitrogen without ingredients was associated with predominant appearance of apoptotic cells after thawing and re-culture, progressive growth of MSC was observed following use of cryo-medium. Moreover, conditioning of UC tissue pieces by initial explant culture and subsequent cryo-storage with cryo-medium accelerated a further MSC culture after thawing. These findings suggested that conditioning of UC tissue pieces provides an in vitro stem cell niche by maintenance of a 3-dimensional natural microenvironment for continuous MSC outgrowth and expansion. Indeed, culture of GFP-labeled UC tissue pieces was accompanied by increased outgrowth of GFP-labeled cells which was accelerated in conditioned UC tissue after cryo-storage. Moreover, cryopreserved conditioned UC tissue pieces in cryo-medium after thawing and explant culture could be cryopreserved again demonstrating renewed MSC outgrowth after repeated thawing with similar population doublings compared to the initial explant culture. Flow cytometry analysis of outgrowing cells revealed expression of the typical MSC markers CD73, CD90, and CD105. Furthermore, these cells demonstrated little if any senescence and cultures revealed stem cell-like characteristics by differentiation along the adipogenic, chondrogenic and osteogenic lineages. CONCLUSIONS: Expression of MSC markers was maintained for at least 10 freeze/thaw/explant culture cycles demonstrating that repeated cryopreservation of conditioned UC tissue pieces provided a reproducible and enriched stem cell source. PMID- 26869168 TI - Augmenting the logrank test in the design of clinical trials in which non proportional hazards of the treatment effect may be anticipated. AB - BACKGROUND: Most randomized controlled trials with a time-to-event outcome are designed assuming proportional hazards (PH) of the treatment effect. The sample size calculation is based on a logrank test. However, non-proportional hazards are increasingly common. At analysis, the estimated hazards ratio with a confidence interval is usually presented. The estimate is often obtained from a Cox PH model with treatment as a covariate. If non-proportional hazards are present, the logrank and equivalent Cox tests may lose power. To safeguard power, we previously suggested a 'joint test' combining the Cox test with a test of non proportional hazards. Unfortunately, a larger sample size is needed to preserve power under PH. Here, we describe a novel test that unites the Cox test with a permutation test based on restricted mean survival time. METHODS: We propose a combined hypothesis test based on a permutation test of the difference in restricted mean survival time across time. The test involves the minimum of the Cox and permutation test P-values. We approximate its null distribution and correct it for correlation between the two P-values. Using extensive simulations, we assess the type 1 error and power of the combined test under several scenarios and compare with other tests. We investigate powering a trial using the combined test. RESULTS: The type 1 error of the combined test is close to nominal. Power under proportional hazards is slightly lower than for the Cox test. Enhanced power is available when the treatment difference shows an 'early effect', an initial separation of survival curves which diminishes over time. The power is reduced under a 'late effect', when little or no difference in survival curves is seen for an initial period and then a late separation occurs. We propose a method of powering a trial using the combined test. The 'insurance premium' offered by the combined test to safeguard power under non-PH represents about a single-digit percentage increase in sample size. CONCLUSIONS: The combined test increases trial power under an early treatment effect and protects power under other scenarios. Use of restricted mean survival time facilitates testing and displaying a generalized treatment effect. PMID- 26869169 TI - Evaluation of laboratory perspectives on hereditary cancer panels. AB - Genetic counseling and testing for hereditary cancer susceptibility is a rapidly evolving field and partly a result of next-generation sequencing (NGS) allowing analysis of multiple cancer susceptibility genes simultaneously. This qualitative study explored laboratory perspectives on hereditary cancer panels. Semi structured interviews were conducted with representatives of clinical laboratories offering hereditary cancer panels via NGS. Several themes emerged from the responses pertaining to hereditary cancer panel development, the importance of communication of panel properties with patients, variant reporting policies, and the future of hereditary cancer gene testing. Clinical utility was discussed as primary consideration during panel development. In addition, while participants indicated gene and syndrome overlap prompted panel development in general, laboratories differed in their opinions of whether phenotypic overlap warrants offering pan-cancer panels only versus cancer specific panels. Participants stressed the importance of patients understanding implications of panel testing, including what is tested for and limitations of testing. While all laboratories discussed the limitations of a variant of uncertain significance result, they differed significantly in their reporting methods. This study provides healthcare providers information on the laboratory approach to panel testing, highlighting both commonalities and differences in laboratory approaches, and may allow providers to make more informed decisions when ordering hereditary cancer panels. PMID- 26869171 TI - Is rationale to decrease serum osteoprotegerin and fetuin-A in type 2 diabetes mellitus patients? AB - Fetuin-A and osteoprotegerin (OPG) are considered biomarkers of atherosclerosis, vascular calcification, inflammation in subjects with type 2 diabetes mellitus (T2DM) with possible predictive value. Recent clinical studies have been shown that fetuin-A and OPG could be helpful for cardiovascular risk stratification in T2DM. Therefore, fetuin-A and OPG may offer protection against atherosclerosis and vascular calcification. However, clinical implication of decreased serum concentrations of these biomarkers in T2DM during treatment with thiazolidinediones, in particular pioglitazone, and metformin is not fully understood. The relation of thiazolidinediones- and metformin- induced post treatment serum levels of fetuin-A and OPG to changes in CV risk requires more investigations. PMID- 26869170 TI - Controversies in the surgery of patients with familial adenomatous polyposis and Lynch syndrome. AB - Dominantly inherited syndromes of colorectal cancer predisposition are characterized by multifocal neoplasia with an early age of onset. The risk of colorectal cancer is high in affected patients and care of the patients is based on the aims of cancer prevention and cancer cure. At the same time, quality of life should be disturbed as little as possible. Because patients are generally young, the stakes are high. Injudicious decision-making can have unfortunate effects on patients and families. In this article the controversial aspects of surgery in familial adenomatous polyposis and Lynch syndrome are discussed. Specifically the controversies in familial adenomatous polyposis include the timing and the type of surgery while for Lynch syndrome discussion revolves about prophylactic surgery, primary, secondary and tertiary. PMID- 26869172 TI - MicroRNAs in heart failure: from biomarker to target for therapy. AB - MicroRNAs (miRNAs) are increasingly recognized to play important roles in cardiovascular diseases, including heart failure. These small, non-coding RNAs have been identified in tissue and are involved in several pathophysiological processes related to heart failure, such as cardiac fibrosis and hypertrophy. As a result, miRNAs have become interesting novel drug targets, leading to the development of miRNA mimics and antimirs. MicroRNAs are also detected in the circulation, and are proposed as potential diagnostic and prognostic biomarkers in heart failure. However, their role and function in the circulation remains to be resolved. Here, we review the potential roles of miRNAs as circulating biomarkers and as targets for therapy. PMID- 26869173 TI - Exploration of Antiemetics for Osteoporosis Therapy-Induced Nausea and Vomiting Using PET Molecular Imaging Analysis to Gastrointestinal Pharmacokinetics. AB - PURPOSE: To select appropriate antiemetics relieving teriparatide-induced nausea and vomiting during osteoporosis treatment using PET molecular imaging and pharmacokinetic analysis. METHODS: Rats were pretreated with subcutaneous teriparatide, followed by oral administration of antiemetics with different pharmacological effects. The pharmacokinetics of antiemetics were assessed by oral administration of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) under free moving conditions in vivo. The effect of teriparatide on the permeability of Caco 2 cell membranes to [(18)F]FDG was assessed in vitro. The effects of antiemetics on teriparatide-induced suppression of gastrointestinal motility in vivo was assayed by positron emission tomography (PET) using orally administered [(18)F]FDG. RESULTS: Teriparatide delayed the time-radioactivity profile of [(18)F]FDG in blood and significantly reduced its absorption rate constant (k a ), determined from non-compartmental analysis, to 60% of control. In contrast, co administration of granisetron or mosapride restored the time-radioactivity profile and k a of [(18)F]FDG to control levels. Teriparatide had no effect on Caco-2 membrane permeability to [(18)F]FDG. Pharmacokinetic PET imaging data analysis quantitatively showed the pharmacological effects of teriparatide induced suppression of upper gastrointestinal motility and its restoration by granisetron and mosapride. CONCLUSIONS: Teriparatide-induced abdominal discomfort might be attributed to GI motility, and PET imaging analysis is a useful tool to for the selection of appropriate antiemetics. PMID- 26869175 TI - Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4). AB - PURPOSE: To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations. METHODS: Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets. RESULTS: PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5 s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems. CONCLUSIONS: Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems. PMID- 26869174 TI - Evaluation of Time Dependent Inhibition Assays for Marketed Oncology Drugs: Comparison of Human Hepatocytes and Liver Microsomes in the Presence and Absence of Human Plasma. AB - PURPOSE: To evaluate an alternative in vitro system which can provide more quantitatively accurate drug drug interaction (DDI) prediction for 10 protein kinase inhibitors for which DDI risk was over-predicted by inhibition data generated in human liver microsomes (HLM). METHODS: Three cryopreserved human hepatocyte (hHEP) systems: 1) plated hHEPs; 2) hHEPs suspended in Dulbecco's Modified Eagle Medium (DMEM) and 3) hHEPs suspended in human plasma (plasma hHEPs) were developed to detect CYP3A time dependent inhibition, and the static mechanistic model was used to predict clinical outcomes. RESULTS: A general trend was observed in the CYP3A inactivation potency (k inact /K I, app ) as HLM > plated > DMEM >= plasma hHEPs. Using the static mechanistic model, DDIs predicted using parameters estimated from plated, DMEM and plasma hHEPs had 84, 74 and 95% accuracy (out of 19 clinical interaction studies) within 2-fold of the reported interaction, respectively. They demonstrated significant improvement compared to the DDIs predicted using parameters estimated from HLMs where 58% accuracy was obtained. CONCLUSIONS: Based on 19 DDIs, plasma hHEPs demonstrate a more reliable clinical DDI prediction for 10 protein kinase inhibitors and prototypical CYP3A time dependent inhibitors. PMID- 26869179 TI - Correction. PMID- 26869178 TI - In vivo regeneration of bladder muscular wall using decellularized colon matrix: an experimental study. AB - BACKGROUND: Finding a proper scaffold for augmentation is a serious challenge in bladder tissue engineering. We hereby aimed to determine the histological aspects of a decellularized colon graft for bladder augmentation in healthy rats. METHODS: Rat colon tissues were decellularized using perfusion-based method. After partial cystectomy, bladders were grafted with a patch of decellularized colon. Bladder specimens were investigated in 12 rats at 1, 3, and 9 months postoperatively for further histological changes and immunohistochemistry analyses were also performed. RESULTS: One month after implantation, partial seeding of new cells was observed. After 3 months continuity of transitional epithelium of natural bladder on the decellularized grafted colon tissue was confirmed with histological and immunohistochemical examinations. All augmented bladders demonstrated a spherical shape without stone formation, necrosis or graft rejection. The presence of urothelium with similar morphology to the natural urothelium and visible blood vessels were found within 3 months of operation. All immunohistochemical markers (except markers of colonic stem cells) were expressed in biopsies obtained 3 months after surgery demonstrating a progressive vascular and smooth muscle cell infiltration into the graft after implantation. CONCLUSION: This study suggests that decellularized colon may provide a viable material for bladder augmentation in rats to pave the road for future applications of this natural collagen scaffold. PMID- 26869177 TI - Facilitators for the development and implementation of health promoting policy and programs - a scoping review at the local community level. AB - BACKGROUND: Health promotion, with a focus on multidimensional upstream factors and an ecological, life-course approach, is establishing itself as the guiding philosophy for addressing public health. Action at the political and programmatic level on the Social Determinants of Health has proven effective for promoting and building public health at all levels but has been particularly evident at the national and international levels - due in large part to available documents and guidelines. Although research and experience establish that health promotion is most effective when settings-based, the development of health promoting policies and programs at the local level is still difficult. This study intended to investigate available knowledge on the development and implementation of health promoting policies and programs at the local level and identify factors most important for facilitating capacity building and outcome achievement. METHODS: We used a scoping review in order to review the current literature on local policy development and program implementation. Keywords were chosen based on results of a previous literature review. A total of 53 articles were divided into two categories: policy and implementation. Critical analysis was conducted for each article and a summary assembled. Data was charted with specific focus on the aims of the study, data acquisition, key theories/concepts/frameworks used, outcome measures, results, and conclusions. RESULTS: The articles included in this study primarily focused on discussing factors that facilitate the development of health promoting policy and the implementation of health promotion programs. Most significant facilitators included: collaborative decision-making, agreement of objectives and goals, local planning and action, effective leadership, building and maintaining trust, availability of resources, a dynamic approach, a realistic time-frame, and trained and knowledgeable staff. Within each of these important facilitating factors, various elements supporting implementation were discussed and highlighted in this study. CONCLUSION: Our results indicate that clear and consistent facilitators exist for supporting health promoting policy development and program implementation at the local level. These results offer a starting point for local action on the Social Determinants of Health and have the potential to contribute to the development of a framework for improving action at the local level. PMID- 26869176 TI - Bipolar disorder and antithyroid antibodies: review and case series. AB - Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms. PMID- 26869180 TI - Land use imperils plant and animal community stability through changes in asynchrony rather than diversity. AB - Human land use may detrimentally affect biodiversity, yet long-term stability of species communities is vital for maintaining ecosystem functioning. Community stability can be achieved by higher species diversity (portfolio effect), higher asynchrony across species (insurance hypothesis) and higher abundance of populations. However, the relative importance of these stabilizing pathways and whether they interact with land use in real-world ecosystems is unknown. We monitored inter-annual fluctuations of 2,671 plant, arthropod, bird and bat species in 300 sites from three regions. Arthropods show 2.0-fold and birds 3.7 fold higher community fluctuations in grasslands than in forests, suggesting a negative impact of forest conversion. Land-use intensity in forests has a negative net impact on stability of bats and in grasslands on birds. Our findings demonstrate that asynchrony across species--much more than species diversity alone--is the main driver of variation in stability across sites and requires more attention in sustainable management. PMID- 26869182 TI - Clinical effectiveness and cost-effectiveness of body psychotherapy in the treatment of negative symptoms of schizophrenia: a multicentre randomised controlled trial. AB - BACKGROUND: The negative symptoms of schizophrenia significantly impact on quality of life and social functioning, and current treatment options are limited. In this study the clinical effectiveness and cost-effectiveness of group body psychotherapy as a treatment for negative symptoms were compared with an active control. DESIGN: A parallel-arm, multisite randomised controlled trial. Randomisation was conducted independently of the research team, using a 1 : 1 computer-generated sequence. Assessors and statisticians were blinded to treatment allocation. Analysis was conducted following the intention-to-treat principle. In the cost-effectiveness analysis, a health and social care perspective was adopted. PARTICIPANTS: ELIGIBILITY CRITERIA: age 18-65 years; diagnosis of schizophrenia with symptoms present at > 6 months; score of >= 18 on Positive and Negative Syndrome Scale (PANSS) negative symptoms subscale; no change in medication type in past 6 weeks; willingness to participate; ability to give informed consent; and community outpatient. EXCLUSION CRITERIA: inability to participate in the groups and insufficient command of English. SETTINGS: Participants were recruited from NHS mental health community services in five different Trusts. All groups took place in local community spaces. INTERVENTIONS: Control intervention: a 10-week, 90-minute, 20-session group beginners' Pilates class, run by a qualified Pilates instructor. Treatment intervention: a 10-week, 90-minute, 20-session manualised group body psychotherapy group, run by a qualified dance movement psychotherapist. OUTCOMES: The primary outcome was the PANSS negative symptoms subscale score at end of treatment. Secondary outcomes included measures of psychopathology, functional, social, service use and treatment satisfaction outcomes, both at treatment end and at 6-month follow-up. RESULTS: A total of 275 participants were randomised (140 body psychotherapy group, 135 Pilates group). At the end of treatment, 264 participants were assessed (137 body psychotherapy group, 127 Pilates group). The adjusted difference in means of the PANSS negative subscale at the end of treatment was 0.03 [95% confidence interval (CI) -1.11 to 1.17], showing no advantage of the intervention. In the secondary outcomes, the mean difference in the Clinical Assessment Interview for negative symptoms expression subscale at the end of treatment was 0.62 (95% CI -1.23 to 0.00), and in extrapyramidal movement disorder symptoms -0.65 (95% CI -1.13 to -0.16) at the end of treatment and -0.58 (95% CI -1.07 to -0.09) at 6 months' follow-up, showing a small significant advantage of body psychotherapy. No serious adverse events related to the interventions were reported. The total costs of the intervention were comparable with the control, with no clear evidence of cost-effectiveness for either condition. LIMITATIONS: Owing to the absence of a treatment-as-usual arm, it is difficult to determine whether or not both arms are an improvement over routine care. CONCLUSIONS: In comparison with an active control, group body psychotherapy does not have a clinically relevant beneficial effect in the treatment of patients with negative symptoms of schizophrenia. These findings conflict with the review that led to the current National Institute for Health and Care Excellence guidelines suggesting that arts therapies may be an effective treatment for negative symptoms. FUTURE WORK: Determining whether or not this lack of effectiveness extends to all types of art therapies would be informative. TRIAL REGISTRATION: Current Controlled Trials ISRCTN842165587. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 11. See the NIHR Journals Library website for further project information. PMID- 26869181 TI - Improving access to primary care for Aboriginal babies in Western Australia: study protocol for a randomized controlled trial. AB - BACKGROUND: Despite a decade of substantial investments in programs to improve access to primary care for Aboriginal mothers and infants, more than 50% of Western Australian Aboriginal babies are still not receiving primary and preventative care in the early months of life. Western Australian hospitals now input birth data into the Western Australian electronic clinical management system within 48 hours of birth. However, difficulties have arisen in ensuring that the appropriate primary care providers receive birth notification and clinical information by the time babies are discharged from the hospital. No consistent process exists to ensure that choices about primary care are discussed with Aboriginal families. METHODS/DESIGN: We will undertake a population-based, stepped wedge, cluster randomized controlled trial of an enhanced model of early infant primary care. The intervention is targeted support and care coordination for Aboriginal families with new babies starting as soon as possible during the antenatal period or after birth. Dedicated health professionals and research staff will consult with families about the families' healthcare needs, provide information about healthcare in the first 3 months of life, offer assistance with birth and Medicare forms, consult with families about their choice for primary care provider, offer to notify the chosen primary care provider about the baby's health needs, and offer assistance with healthcare coordination at the time of discharge from the hospital. We will evaluate this model of care using a rigorous stepped wedge approach. Our primary outcome measure is a reduced hospitalization rate in infants younger than 3 months of age. Secondary outcome measures include completed Aboriginal and Torres Strait Islander child health screening assessments, immunization coverage, and satisfaction of the families about early infant primary care. We will also assess the cost effectiveness of the model of care. DISCUSSION: This study will be conducted over a 4-year period in partnership with birthing hospitals and primary care providers including Western Australian Aboriginal Community Controlled Health Services and the new Primary Health Networks. The results of our trial will be used to develop improved primary care models and to improve health outcomes for all Aboriginal infants. These are vital steps toward more equitable health service delivery for the Aboriginal and Torres Strait Islander children in Australia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Registration number: ACTRN12615000976583 Date registered: 17 September 2015. PMID- 26869185 TI - Factors Associated with HIV Testing among African American Female Adolescents in Juvenile Detention Centers. AB - BACKGROUND: Little is known about sexual and psychosocial factors associated with HIV testing among detained African American female adolescents-an understudied group at risk for HIV. METHODS: 188 detained African American female adolescents completed assessments on HIV testing, sexual risk behaviors, and psychosocial factors. RESULTS: Unprotected vaginal sex, history of STI-positivity or pregnancy, higher STI knowledge, and lower partner availability were associated with a higher likelihood of ever being tested for HIV. DISCUSSION: HIV testing is the gateway to important services for high-risk HIV-positive and HIV-negative adolescents. More research is needed to address barriers and to inform programmatic changes to increase testing among youth. PMID- 26869183 TI - Prostaglandin I2 Attenuates Prostaglandin E2-Stimulated Expression of Interferon gamma in a beta-Amyloid Protein- and NF-kappaB-Dependent Mechanism. AB - Cyclooxygenase-2 (COX-2) has been recently identified as being involved in the pathogenesis of Alzheimer's disease (AD). However, the role of an important COX-2 metabolic product, prostaglandin (PG) I2, in AD development remains unknown. Using mouse-derived astrocytes as well as APP/PS1 transgenic mice as model systems, we firstly elucidated the mechanisms of interferon gamma (IFNgamma) regulation by PGE2 and PGI2. Specifically, PGE2 accumulation in astrocytes activated the ERK1/2 and NF-kappaB signaling pathways by phosphorylation, which resulted in IFNgamma expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 on stimulating the production of IFNgamma via inhibiting the translocation of NF-kappaB from the cytosol to the nucleus. Due to these observations, we further studied these prostaglandins and found that both PGE2 and PGI2 increased Abeta1-42 levels. In detail, PGE2 induced IFNgamma expression in an Abeta1-42-dependent manner, whereas PGI2-induced Abeta1-42 production did not alleviate cells from IFNgamma inhibition by PGI2 treatment. More importantly, our data also revealed that not only Abeta1-42 oligomer but also fibrillar have the ability to induce the expression of IFNgamma via stimulation of NF-kappaB nuclear translocation in astrocytes of APP/PS1 mice. The production of IFNgamma finally accelerated the deposition of Abeta1-42 in beta amyloid plaques. PMID- 26869184 TI - Prognostic indicators based on inflammatory and nutritional factors after pancreaticoduodenectomy for pancreatic cancer. AB - PURPOSE: We evaluated prognostic indicators based on inflammatory and nutritional factors, namely, the modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR), to determine their efficiency and significance after pancreaticoduodenectomy for pancreatic cancer. METHODS: The subjects of this study were 46 patients who underwent pancreaticoduodenectomy for pancreatic cancer between October 2007 and December 2014. Patients were divided into preoperative mGPS (0/1 and 2), PNI (<40 and >=40), NLR (<2.5 and >=2.5), and PLR (<200 and >=200) groups, to evaluate various perioperative outcomes. RESULTS: Hemoglobin concentrations were significantly lower (P = 0.019), whereas intra abdominal bleeding was significantly higher (P = 0.040) in the PNI (<40) group than in the PNI (>=40) group. The incidence of postoperative pneumonia was significantly higher in the mGPS (2) group (P = 0.009), and surgical complications greater than grade 3 (Clavien-Dindo classification) were significantly increased in the NLR (>=2.5) group (P = 0.041). Overall survival rates in the PNI (<40) (P = 0.019), NLR (>=2.5) (P = 0.001), and PLR (>=200) (P < 0.001) groups were significantly lower than those in the other groups. The PLR was the only independent prognostic indicator (P = 0.002) according to multivariate analysis. CONCLUSIONS: The mGPS, PNI, and NLR were effective predictive indicators of postoperative complications. The PLR was the most useful prognostic indicator for pancreatic cancer patients after pancreaticoduodenectomy. PMID- 26869186 TI - Re-evaluation of batoid pectoral morphology reveals novel patterns of diversity among major lineages. AB - Batoids (Chondrichthyes: Batoidea) are a diverse group of cartilaginous fishes which comprise a monophyletic sister lineage to all neoselachians or modern sharks. All species in this group possess anteroposteriorly expanded-pectoral fins, giving them a unique disc-like body form. Reliance on pectoral fins for propulsion ranges from minimal (sawfish) to almost complete dependence (skates and rays). A recent study on the diversity of planform pectoral fin shape in batoids compared overall patterns of morphological variation within the group. However, inconsistent pectoral homology prevented the study from accurately representing relationships within and among major batoid taxa. With previous work in mind, we undertook an independent investigation of pectoral form in batoids and evaluated the implications of shape diversity on locomotion and lifestyle, particularly in the skates (Rajoidei) and rays (Myliobatoidei). We used geometric morphometrics with sliding semilandmarks to analyze pectoral fin outlines and also calculate fin aspect ratios (AR), a functional trait linked to locomotion. In agreement with previous work, our results indicated that much of the evolution of batoid pectoral shape has occurred along a morphological axis that is closely related to AR. For species where kinematic data were available, both shape and AR were associated with swimming mode. This work further revealed novel patterns of shape variation among batoids, including strong bimodality of shape in rays, an intermediate location of skate species in the morphospace between benthic/demersal and pelagic rays, and approximately parallel shape trajectories in the benthic/demersal rays and skates. Finally, manipulation of landmarks verified the need for a consistent and accurate definition of homology for the outcome and efficacy of analyses of pectoral form and function in batoids. PMID- 26869187 TI - Origin of colossal dielectric permittivity of rutile Ti0.9In0.05Nb0.05O2: single crystal and polycrystalline. AB - In this paper, we investigated the dielectric properties of (In + Nb) co-doped rutile TiO2 single crystal and polycrystalline ceramics. Both of them showed colossal, up to 10(4), dielectric permittivity at room temperature. The single crystal sample showed one dielectric relaxation process with a large dielectric loss. The voltage-dependence of dielectric permittivity and the impedance spectrum suggest that the high dielectric permittivity of single crystal originated from the surface barrier layer capacitor (SBLC). The impedance spectroscopy at different temperature confirmed that the (In + Nb) co-doped rutile TiO2 polycrystalline ceramic had semiconductor grains and insulating grain boundaries, and that the activation energies were calculated to be 0.052 eV and 0.35 eV for grain and grain boundary, respectively. The dielectric behavior and impedance spectrum of the polycrystalline ceramic sample indicated that the internal barrier layer capacitor (IBLC) mode made a major contribution to the high ceramic dielectric permittivity, instead of the electron-pinned defect dipoles. PMID- 26869189 TI - Stem Cells Antigen-1 Enriches for a Cancer Stem Cell-Like Subpopulation in Mouse Gastric Cancer. AB - There is a strong need to identify markers to enrich gastric cancer stem cells (CSCs). However, CSC enrichment markers for mouse gastric cancers have not yet been determined. In our previous study, we generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4(F/F) ;Trp53(F/F) ;Cdh1(F/wt) mouse and its metastatic variant cell line NCC-S1M (S1M). Interestingly, S1M cells exhibited CSC-like features, such as increased tumorigenic potential and chemoresistance. By comparing gene expression profiles between S1 and S1M cells, we identified Stem Cells Antigen-1 (Sca-1) as a cell surface marker, which was mostly upregulated in S1M. Sca-1 was upregulated in tumorspheres from S1 cells or after cisplatin treatment in S1 cells. Immunofluorescence (IF) analysis showed that approximately 7% of cancer cells exhibited positivity for Sca-1 in primary mouse gastric cancer tissues. An in vivo-limiting dilution assay showed that Sca-1(high) mouse gastric cancer cells demonstrated increased tumorigenicity compared with Sca-1(negative) cells. The Sca-1 expression was downregulated by TGF-beta pathway activation and Wnt pathway inhibition in mouse gastric cancer cells. Sca-1(high) cells showed relatively low TGF-beta reporter activity and high TCF/LEF1 reporter activity compared with Sca 1(negative) cells. A chromatin immunoprecipitation analysis demonstrated that Sca 1 was a beta-catenin/LEF1 target gene. Sca-1(high) allografts were more resistant to cisplatin/fluorouracil chemotherapy than Sca-1(negative) allografts, and overexpressed Bcl-xL. Eighty-five mouse genes overexpressed in Sca-1(high) S1 cells compared with Sca-1(negative) cells clustered 123 pretreatment gastric cancer patient samples according to survival following chemotherapy. Taken together, Sca-1 is a novel CSC enrichment marker that mediates TGF-beta and Wnt/beta-catenin signaling in mouse gastric cancer. Stem Cells 2016;34:1177-1187. PMID- 26869188 TI - Health Services Research and Regionalization of Care-From Policy to Practice: the Ontario Experience in Head and Neck Cancer. AB - Patients being treated at higher case volume hospitals or by higher case volume physicians appear to have better outcomes. This volume-outcome relationship is reviewed for oncologic and non-oncologic surgery with a focus on head and neck oncology. The impact of these research findings on health policy and health-care organization in Ontario, Canada, is then outlined. Lastly, future directions for quality improvement in surgical oncology are reviewed in the context of a universal health-care system. These include surgeon report cards, pre-operative checklists, linking funding and remuneration to the quality of delivered care, and the use of process improvement techniques. PMID- 26869190 TI - New Formulations of Old Analgesics and Repurposing of Old Drugs as "New" Analgesics. PMID- 26869192 TI - Improvement of Pediatric Drug Development: Regulatory and Practical Frameworks. AB - PURPOSE: A dearth in pediatric drug development often leaves pediatricians with no alternative but to prescribe unlicensed or off-label drugs with a resultant increased risk of adverse events. We present the current status of pediatric drug development and, based on our data analysis, clarify the problems in this area. Further action is proposed to improve the drug development that has pediatric therapeutic orphan status. METHODS: We analyzed all Phase II/III and Phase III trials in ClinicalTrials.gov that only included pediatric participants (<18 years old) between 2006 and 2014. Performance index, an indicator of pediatric drug development, was calculated by dividing the annual number of pediatric clinical trials by million pediatric populations acquired from Census.gov. Effects of the 2 Japanese premiums introduced in 2010, for the enhancement of pediatric drug development, were analyzed by comparing mean performance index prepremiums (2006 2009) and postpremiums (2010-2014) among Japan, the European Union, and the United States. The European Union Clinical Trials Register and published reports from the European Medicines Agency were also surveyed to investigate the Paediatric Committee effect on pediatric clinical trials in the European Union. FINDINGS: Mean difference of the performance index in prepremiums and postpremiums between Japan and the European Union were 0.296 (P < 0.001) and 0.066 (P = 0.498), respectively. Those between Japan and the United States were 0.560 (P < 0.001) and 0.281 (P = 0.002), indicating that pediatric drug development in Japan was more active after the introduction of these premiums, even reaching the level of the European Union. The Pediatric Regulation and the Paediatric Committee promoted pediatric drug development in the European Union. The registered number of clinical trials that includes at least 1 participants <18 years old in the European Union Clinical Trials Register increased by 247 trials (from 672) in the 1000 days after regulation. The ratio of pediatric clinical trials with an approved Paediatric Investigation Plan increased to >15% after 2008. IMPLICATIONS: Recruitment and ethical obstacles make conducting pediatric clinical trials challenging. An improved operational framework for conducting clinical trials should mirror the ever-improving regulatory framework that incentivizes investment in pediatric clinical trials. Technological approaches, enhancements in electronic medical record systems, and community approaches that actively incorporate input from physicians, researchers, and patients could offer a sustainable solution to recruitment of pediatric study participants. The key therefore is to improve pediatric pharmacotherapy collaboration among industry, government, academia, and community. Expanding the regulatory steps taken in the European Union, United States, and Japan and using innovative clinical trial tools can move pediatric pharmacotherapy out of its current therapeutic orphan state. PMID- 26869191 TI - Pharmacokinetic and Pharmacodynamic Effects of Multiple-dose Administration of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 Inhibitor, in Obese Participants With and Without Type 2 Diabetes Mellitus. AB - PURPOSE: Omarigliptin (MK-3102) is a potent, oral, long-acting dipeptidyl peptidase (DPP)-4 inhibitor approved in Japan and in global development as a once weekly treatment for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) effects of omarigliptin in obese participants with and without T2DM. METHODS: This was a Phase I, randomized, double-blind, placebo-controlled, multiple-dose study of 50 mg omarigliptin administered once weekly for 4 weeks. Participants included 24 obese but otherwise healthy subjects (panel A; omarigliptin, n = 18; placebo, n = 6) and 8 obese patients with T2DM (treatment naive, hemoglobin A1c >= 6.5% and <= 10.0% [panel B]; omarigliptin, n = 6; placebo, n = 2). Participants were 45 to 65 years of age with a body mass index of >= 30 and <= 40 kg/m(2). Blood sampling occurred at select time points, depending on the study panel, to evaluate the PK properties of omarigliptin, DPP-4 activity, active glucagon-like peptide 1 levels, and plasma glucose concentrations. Body weight was an exploratory end point. Due to sparse sampling in panel A, a thorough PK analysis was performed in obese patients with T2DM (panel B) only. PD analyses were performed in the overall study population (pooled panels A and B). FINDINGS: PK profiles in obese participants with and without T2DM were similar to those observed in nonobese reference subjects (historical data). Steady state was achieved after 1 or 2 weekly doses in obese participants with and without T2DM. In obese patients with T2DM, omarigliptin was rapidly absorbed, with a median Tmax of 1 to 2.5 hours (days 1 and 22). Compared with those in reference subjects, the geometric mean ratios (95% CI) (Obese T2DM/reference) for steady-state plasma AUC0-168h, Cmax, and C168h were 0.80 (0.65-0.98), 0.86 (0.53-1.41), and 1.08 (0.88-1.33), respectively. Trough DPP-4 activity was inhibited by ~90%; postprandial (PP) 4 hour weighted mean active GLP-1 concentrations were increased ~2-fold; and PP glucose was significantly reduced with omarigliptin versus placebo in the pooled population. Omarigliptin was generally well-tolerated in the pooled population, and there were no hypoglycemic events. Consistent with other DPP-4 inhibitors, omarigliptin had no effect on body weight in this short-duration study. IMPLICATIONS: The administration of omarigliptin was generally well-tolerated in obese participants with and without T2DM, and the favorable PK and PD profiles support once-weekly dosing. Omarigliptin may provide an important once-weekly treatment option for patients with T2DM. ClinicalTrials.gov identifier: NCT01088711. PMID- 26869193 TI - In silico to in vitro screening of hydroxypyridinones as acetylcholinesterase inhibitors. AB - We have previously shown the improved acetylcholinesterase inhibitory activity of a model hydroxypyridinone compound transforming the hydroxyl group on the main ring into an N,N-dimethylcarbamate group; in the course of that study we developed a computational model to screen compounds for enzymatic activity. Herein we report development of second generation libraries. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies. Synthesis and characterization of chosen test compounds and their acetylcholinesterase inhibitory activity are presented. PMID- 26869194 TI - A phenotypic drug discovery study on thienodiazepine derivatives as inhibitors of T cell proliferation induced by CD28 co-stimulation leads to the discovery of a first bromodomain inhibitor. AB - A phenotypic screening of thienodiazepines derived from a hit compound found through a binding assay targeting co-stimulatory molecules on T cells and antigen presenting cells successfully led to the discovery of a thienotriazolodiazepine compound (7f) possessing potent immunosuppressive activity. A chemical biology approach has succeeded in revealing that 7f is a first inhibitor of epigenetic bromodomain-containing proteins. 7f is expected to become an anti-cancer agent as well as an immunosuppressive agent. PMID- 26869195 TI - Floorball-related eye injuries: The impact of protective eyewear. AB - Several previous studies have shown that floorball belongs to a high-risk group of sports in terms of eye injuries. Protective eyewear is available, but the extent of its use and impact on eye injuries are unknown. The purpose of this study was to investigate the current incidence of eye injuries caused by floorball and to compare it with the present use of protective eyewear. Medical records were used to identify all eye injuries suffered while playing floorball in Jonkoping County from 2008 to 2011 (N = 167). All these patients were sent a questionnaire that included inquiries about the use of protective eyewear. The study shows that floorball caused more eye injuries than all other sports combined (56%). Prolonged decreased visual acuity was very unusual (0.5%), but moderate eye injuries with some risk of future problems were seen in 62% of the sample. More than one fifth of the injured patients reported some kind of vision related problem 2-7 years after the original injury. Only one player had been using protective eyewear at the time of injury. Our results underline the importance of protective eyewear to prevent floorball-related injuries. PMID- 26869196 TI - Premenstrual symptoms and smoking-related expectancies. AB - Given that prior research implicates smoking abstinence in increased premenstrual symptoms, tobacco withdrawal, and smoking behaviors, it is possible that women with more severe premenstrual symptoms have stronger expectancies about the effects of smoking and abstaining from smoking on mood and withdrawal. However, such relations have not been previously explored. This study examined relations between premenstrual symptoms experienced in the last month and expectancies that abstaining from smoking results in withdrawal (i.e., smoking abstinence withdrawal expectancies), that smoking is pleasurable (i.e., positive reinforcement smoking expectancies), and smoking relieves negative mood (i.e., negative reinforcement smoking expectancies). In a cross-sectional design, 97 non treatment seeking women daily smokers completed self-report measures of smoking reinforcement expectancies, smoking abstinence withdrawal expectancies, premenstrual symptoms, mood symptoms, and nicotine dependence. Affect premenstrual symptoms were associated with increased negative reinforcement smoking expectancies, but not over and above covariates. Affect and pain premenstrual symptoms were associated with increased positive reinforcement smoking expectancies, but only affect premenstrual symptoms remained significant in adjusted models. Affect, pain, and water retention premenstrual symptoms were associated with increased smoking abstinence withdrawal expectancies, but only affect premenstrual symptoms remained significant in adjusted models. Findings from this study suggest that addressing concerns about withdrawal and alternatives to smoking may be particularly important in women who experience more severe premenstrual symptoms, especially affect-related changes. PMID- 26869198 TI - EDITORIAL. PMID- 26869197 TI - Responses of soil nitrogen fixation to Spartina alterniflora invasion and nitrogen addition in a Chinese salt marsh. AB - Biological nitrogen fixation (BNF) is the major natural process of nitrogen (N) input to ecosystems. To understand how plant invasion and N enrichment affect BNF, we compared soil N-fixation rates and N-fixing microbes (NFM) of an invasive Spartina alterniflora community and a native Phragmites australis community in the Yangtze River estuary, with and without N addition. Our results indicated that plant invasion relative to N enrichment had a greater influence on BNF. At each N level, the S. alterniflora community had a higher soil N-fixation rate but a lower diversity of the nifH gene in comparison with the native community. The S. alterniflora community with N addition had the highest soil N-fixation rate and the nifH gene abundance across all treatments. Our results suggest that S. alterniflora invasion can increase soil N fixation in the high N-loading estuarine ecosystem, and thus may further mediate soil N availability. PMID- 26869199 TI - Cystic fibrosis transmembrane conductance regulator activation by the solvent ethanol: implications for topical drug delivery. AB - BACKGROUND: Decreased cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride (Cl) secretion across mucosal surfaces contributes to the development of airway disease by depleting airway surface liquid, increasing mucus viscosity and adhesion, and consequently hindering mucociliary clearance. We serendipitously discovered during testing of drugs solubilized in low concentrations ethanol (0.25%, 43 mM) that the control vehicle produced robust activation of CFTR-mediated Cl(-) transport. The objective of the current study is to investigate low concentrations of ethanol for effects on Cl(-) secretion and ciliary beat frequency (CBF). METHODS: Wild-type (WT) and transgenic CFTR(-/ ) primary murine nasoseptal epithelial (MNSE) cultures and WT and F508del/F508del human sinonasal epithelial (HSNE) cultures were subjected to transepithelial ion transport measurements using pharmacologic manipulation in Ussing chambers. CBF activation was also monitored. Murine nasal potential difference (NPD) was measured in vivo. RESULTS: Ussing chamber tracings revealed ethanol activated CFTR-mediated Cl transport in a dose-dependent fashion in WT MNSE (n = 4, p < 0.05) and HSNE (n = 4, p < 0.05). Ethanol also significantly increased CBF (fold change) in WT MNSE cultures in a dose-dependent fashion (phosphate-buffered saline [PBS], 1.33 +/- 0.04; 0.25% ethanol, 1.37 +/- 0.09; 0.5% ethanol, 1.53 +/- 0.06 [p < 0.05]; 1% ethanol, 1.62 +/- 0.1 [p < 0.05]). Lack of stimulation in CFTR(-/-) and F508del/F508del cultures indicated activity was dependent on the presence of intact functional CFTR. Ethanol perfusion (0.5%) resulted in a significant -3.5-mV mean NPD polarization when compared to control solution (p < 0.05). CONCLUSION: The observation that brief exposure of ethanol stimulated Cl( ) secretion via CFTR-mediated pathways indicates its possible use as topical aerosol delivered alone or in combination with other CFTR activators for diseases of dysfunctional mucociliary clearance (MCC) in chronic rhinosinusitis (CRS). PMID- 26869202 TI - Comments on "Role of intestinal microbiota in the development of multiple sclerosis". PMID- 26869201 TI - Mitochondrial dysfunction in fibroblasts derived from patients with Niemann-Pick type C disease. AB - Mutations in the NPC1 or NPC2 genes lead to Niemann-Pick type C (NPC) disease, a rare lysosomal storage disorder characterized by progressive neurodegeneration. These mutations result in cholesterol and glycosphingolipid accumulation in the late endosomal/lysosomal compartment. Complications in the storage of cholesterol in NPC1 mutant cells are associated with other anomalies, such as altered distribution of intracellular organelles and properties of the plasma membrane. The pathomechanism of NPC disease is largely unknown. Interestingly, other storage diseases such as Gaucher and Farber diseases are accompanied by severe mitochondrial dysfunction. This prompted us to investigate the effect of absence or dysfunction of the NPC1 protein on mitochondrial properties to confirm or deny a putative relationship between NPC1 mutations and mitochondrial function. This study was performed on primary skin fibroblasts derived from skin biopsies of two NPC patients, carrying mutations in the NPC1 gene. We observed altered organization of mitochondria in NPC1 mutant cells, significant enrichment in mitochondrial cholesterol content, increased respiration, altered composition of the respiratory chain complex, and substantial reduction in cellular ATP level. Thus, a primary lysosomal defect in NPC1 mutant fibroblasts is accompanied by deregulation of the organization and function of the mitochondrial network. PMID- 26869200 TI - Functionally conservative substitutions at cardiac troponin I S43/45. AB - A phospho-null Ala substitution at protein kinase C (PKC)-targeted cardiac troponin I (cTnI) S43/45 reduces myocyte and cardiac contractile function. The goal of the current study was to test whether cTnIS43/45N is an alternative, functionally conservative substitution in cardiac myocytes. Partial and more extensive endogenous cTnI replacement was similar at 2 and 4 days after gene transfer, respectively, for epitope-tagged cTnI and cTnIS43/45N. This replacement did not significantly change thin filament stoichiometry. In functional studies, there were no significant changes in the amplitude and/or rates of contractile shortening and re-lengthening after this partial (2 days) and extensive (4 days) replacement with cTnIS43/45N. The cTnIS43/45N substitution also was not associated with adaptive changes in the myocyte Ca(2+) transient or in phosphorylation of the protein kinase A and C-targeted cTnIS23/24 site. These results provide evidence that cTnIS43/45N is a functionally conservative substitution, and may be appropriate for use as a phospho-null in rodent models designed for studies on PKC modulation of cardiac performance. PMID- 26869203 TI - A semi-synthetic natural product blocks collagen induced arthritis by preferentially suppressing the production of IL-6. AB - Rheumatoid arthritis (RA), an autoimmune-inflammatory disease is characterized by dysregulation of signal transduction pathways, increased production of pro inflammatory cytokines, enhanced leukocyte infiltration into synovial microvascular endothelium, extensive formation of hyper proliferative pannus, degradation of cartilage and bone erosion. Several compounds that abrogate cytokine production demonstrate a therapeutic effect in experimental models of arthritis. In this study, we report that a novel semi-synthetic natural product (Compound A) being a preferential IL-6 inhibitor, is efficacious in a murine model of arthritis. In vitro evaluations of pro-inflammatory cytokine production reveal that Compound A preferentially inhibits induced production of IL-6 and not TNF-alpha from THP-1 cells and isolated human monocytes. Furthermore, Compound A robustly inhibits the spontaneous production of IL-6 from pathologically relevant synovial tissue cells isolated from patients with active RA. In a physiologically relevant assay, Compound A selectively inhibits the activated T cell contact mediated production of IL-6 from human monocytes. Compound A, at pharmacologically efficacious concentrations, does not significantly curtail the LPS-induced activation of p38 MAPKs. In the collagen-induced arthritis (CIA) mouse model (i) macroscopic observations demonstrate that Compound A, administered subcutaneously in a therapeutic regimen, significantly and dose dependently inhibits disease associated increases in articular index and paw thickness; (ii) histological analyses of paw tissues reveal that Compound A prominently diminishes joint destruction, hyperproliferative pannus formation and infiltration of inflammatory cells. Collectively, these results provide direct evidence that Compound A, a novel preferential IL-6 inhibitor, suppresses collagen-induced arthritis, and may be a potential therapeutic for treating patients with active RA. PMID- 26869205 TI - Immune Adaptation to Environmental Influence: The Case of NK Cells and HCMV. AB - The immune system of an individual human is determined by heritable traits and a continuous process of adaptation to a broad variety of extrinsic, non-heritable factors such as viruses, bacteria, dietary components and more. Cytomegalovirus (CMV) successfully infects the majority of the human population and establishes latency, thereby exerting a life-long influence on the immune system of its host. CMV has been shown to influence the majority of immune parameters in healthy individuals. Here we focus on adaptive changes induced by CMV in subsets of Natural Killer (NK) cells, changes that question our very definition of adaptive and innate immunity by suggesting that adaptations of immune cells to environmental influences occur across the entire human immune system and not restricted to the classical adaptive branch of the immune system. PMID- 26869204 TI - HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies. AB - The identification of multiple broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer has facilitated its structural characterization and guided Env immunogen design. Several recent studies constitute progress in utilizing this knowledge for the development of an HIV-1 vaccine that induces bNAbs. Native-like Env trimers can induce autologous NAb responses against resistant (Tier-2) viruses in several animal models. Here we review recent studies aimed at addressing the challenge of driving the strong but narrowly focused NAb responses to Env trimers towards ones with much greater breadth. Among strategies that merit pursuing are using multiple trimers as sequential or simultaneous immunogens, targeting the germline precursors of bNAbs, delivering sequential lineages of trimers derived from infected individuals who developed bNAbs, and presenting trimers as particulate antigens. PMID- 26869206 TI - [Status of cardiac resynchronization therapy in Catalonia, Spain: Results of the prospective multicentric study TRC-CAT]. AB - INTRODUCTION AND OBJECTIVES: Results of cardiac resynchronization therapy (CRT) have been extensively published. However, there is limited data in unselected populations. The objective of the study was to analyse the efficacy and safety of CRT in Catalonia. METHODS: A prospective study was performed of consecutive patients implanted with CRT over one year in 7 university hospitals in Catalonia, representing 90% of the implanted patients. Echocardiographic reverse remodelling was defined as 5 points improvement in left ventricular ejection fraction and clinical responders were defined as patients with an increase>10% of six-minute walk test or one point of New York Heart Association functional class at 12 months. Patients were followed up for one year and hospital admissions and mortality were analyzed. RESULTS: Of the 200 patients included in the study, 99% met the indications of the current CRT clinical guidelines and 68% received CRT with implantable cardioverter-defibrillator. The rate of complications was 12.5%. During follow-up 16 patients (8%) died. Fifty-two percent (104) of the population was considered to respond clinically and 62% (124) presented improved echocardiographic parameters. Compared to the year prior to implant, hospital admissions decreased by 82% (P<.001). CONCLUSIONS: In an unselected population of Catalonia, we observe that CRT was effective and decreased the number of hospital admissions. PMID- 26869209 TI - Selection for uterine capacity improves lifetime productivity of sows. AB - Selection for 11 generations for uterine capacity (UC) increased litter size in gilts by 1.6 more fully formed pigs at birth compared to an unselected control line (CO) despite averaging one less ovulation. The objective of the present study was to quantify line by parity interactions and characterize litter performance traits of sows in each line at later parities. Gilts farrowed in contemporary groups of 19 litters and were maintained through four parities if successfully mated in that contemporary group. A total of 243 litters and 2639 piglets were analyzed. Fixed effects of farrowing group, line, parity (1-4), and two-way interactions involving line were fitted. Sire (n=57) of the sow within farrowing group and line was fitted as a random effect. No significant line by parity interactions were observed. Parity effects were detected (P<0.01) for individual piglet birth weight, pre-weaning gain, and weaning weight. Parity effects were also detected (P<0.05) for total number born, average and total litter birth weight, and average and total litter weaning weight. Selection line differences for litter traits were detected (P<0.05) for number stillborn piglets and approached significance (P=0.06) for number of piglets weaned. Retention of sows in the herd was greater (P<0.05) with an average of 2.33 parities for the UC line females compared to 1.87 parities for the CO line. This resulted in favorable cumulative lifetime productivity of the UC line for total number of piglets born, number of piglets born alive, litter birth weight, number of piglets weaned and litter weaning weight. PMID- 26869208 TI - Pilocarpine-induced seizures trigger differential regulation of microRNA stability related genes in rat hippocampal neurons. AB - Epileptogenesis in the temporal lobe elicits regulation of gene expression and protein translation, leading to reorganization of neuronal networks. In this process, miRNAs were described as being regulated in a cell-specific manner, although mechanistics of miRNAs activity are poorly understood. The specificity of miRNAs on their target genes depends on their intracellular concentration, reflecting the balance of biosynthesis and degradation. Herein, we confirmed that pilocarpine application promptly (<30 min) induces status epilepticus (SE) as revealed by changes in rat electrocorticogram particularly in fast-beta range (21 30 Hz). SE simultaneously upregulated XRN2 and downregulated PAPD4 gene expression in the hippocampus, two genes related to miRNA degradation and stability, respectively. Moreover, SE decreased the number of XRN2-positive cells in the hilus, while reduced the number of PAPD4-positive cells in CA1. XRN2 and PAPD4 levels did not change in calretinin- and CamKII-positive cells, although it was possible to determine that PAPD4, but not XRN2, was upregulated in parvalbumin-positive cells, revealing that SE induction unbalances the accumulation of these functional-opposed proteins in inhibitory interneurons that directly innervate distinct domains of pyramidal cells. Therefore, we were able to disclose a possible mechanism underlying the differential regulation of miRNAs in specific neurons during epileptogenesis. PMID- 26869211 TI - Synthesis of indoles and tryptophan derivatives via photoinduced nitrene C-H insertion. AB - Functionalized indoles and tryptophans can be obtained from stannylated alkenes and o-iodoanilines via Stille coupling. Subsequent azidation and photochemical nitrene generation results in the formation of the heterocyclic ring systems via C-H insertion. PMID- 26869210 TI - Control of Multilayer Networks. AB - The controllability of a network is a theoretical problem of relevance in a variety of contexts ranging from financial markets to the brain. Until now, network controllability has been characterized only on isolated networks, while the vast majority of complex systems are formed by multilayer networks. Here we build a theoretical framework for the linear controllability of multilayer networks by mapping the problem into a combinatorial matching problem. We found that correlating the external signals in the different layers can significantly reduce the multiplex network robustness to node removal, as it can be seen in conjunction with a hybrid phase transition occurring in interacting Poisson networks. Moreover we observe that multilayer networks can stabilize the fully controllable multiplex network configuration that can be stable also when the full controllability of the single network is not stable. PMID- 26869212 TI - Double-layer clustering method to predict protein complexes based on power-law distribution and protein sublocalization. AB - Identifying protein complexes from Protein-protein Interaction Networks (PINs) is fundamental for understanding protein functions and activities in cell. Based on the assumption that protein complexes are highly connected areas in PINs, many algorithms were proposed to identify protein complexes from PINs. However, most of these approaches neglected that not all proteins in complexes are highly connected, and proteins in PINs with different topological properties may form protein complexes in different ways and should be treated differently. In this paper, we proposed a double-layer clustering method based on the power-law distribution (PLCluster). To calculate the centrality scores of nodes, we proposed a Dense-Spread Centrality method. The centrality scores calculated by Dense-Spread Centrality method follow a power-law distribution. Based on the power-law distribution of the centrality scores, PLCluster divides the nodes into two categories: the nodes with very high centrality scores and the nodes with lower centrality scores. Then different strategies are applied to nodes in different categories for detecting protein complexes from the PIN, respectively. Furthermore, the predicted protein complexes, which are inconsistent with the fact that all proteins in a protein complex should be in the same subcellular compartment, are filtered out. Compared with other nine existing methods on a high reliable yeast PIN, PLCluster shows great advantages in terms of the number of known complexes that are identified, Sensitivity, Specificity, f-measure and the number of perfect matches. PMID- 26869213 TI - Honesty through repeated interactions. AB - In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID- 26869214 TI - Game theoretic treatments for the differentiation of functional roles in the transition to multicellularity. AB - Multicellular organisms are characterised by role specialisation, brought about by the epigenetic differentiation of their constituent parts. Conventional game theoretic studies of cooperation do not account for this division of labour, nor do they allow for the possibility of the plastic expression of phenotype. We address these issues by extending the notion of cooperative dilemmas to account for such interaction in which heterogeneous roles are advantageous and present an extended dynamical model of selection that allows for the possibility of conditional expression of phenotype. We use these models to investigate systematically when selection will favour an adaptive diversification of roles. We argue that such extensions to models and concepts are necessary to understand the origins of multicellularity and development. PMID- 26869216 TI - Phosphine oxide surfactants revisited. AB - This review summarizes everything we currently know about the nonionic surfactants alkyl dimethyl (C(n)DMPO) and alkyl diethyl (C(n)DEPO) phosphine oxide (PO surfactants). The review starts with the synthesis and the general properties (Section 2) of these compounds and continues with their interfacial properties (Section 3) such as surface tension, surface rheology, interfacial tension and adsorption at solid surfaces. We discuss studies on thin liquid films and foams stabilized by PO surfactants (Section 4) as well as studies on their self-assembly into lyotropic liquid crystals and microemulsions, respectively (Section 5). We aim at encouraging colleagues from both academia and industry to take on board PO surfactants whenever possible and feasible because of their broad variety of excellent properties. PMID- 26869215 TI - A theoretical framework to identify invariant thresholds in infectious disease epidemiology. AB - Setting global strategies and targets for disease prevention and control often involves mathematical models. Model structure is typically subject to intense scrutiny, such as confrontation with empirical data and alternative formulations, while a less frequently challenged aspect is the widely adopted reduction of parameters to their average values. Focusing on endemic diseases, we use a general transmission model to explain how mean field approximations decrease the estimated R0 from prevalence data, while threshold phenomena - such as the epidemic and reinfection thresholds - remain invariant. This results in an underestimation of the effort required to control disease, which may be particularly severe when the approximation inappropriately places transmission estimates below important thresholds. These concepts are widely applicable across endemic pathogen systems. PMID- 26869217 TI - Dimensional assessment of behavioral changes in the cuprizone short-term exposure model for psychosis. AB - Recent clinical studies have suggested a role for immune/inflammatory responses in the pathophysiology of psychosis. However, a mechanistic understanding of this process and its application for drug discovery is underdeveloped. Here we assessed our recently developed cuprizone short-term exposure (CSE) mouse model across behavioral domains targeting neurocognitive and neuroaffective systems. We propose that the CSE model may be useful for understanding the mechanism associating inflammation and psychosis, with applications for drug discovery in that context. PMID- 26869220 TI - I saw where you have been--The topography of human demonstration affects dogs' search patterns and perseverative errors. AB - Performance in object search tasks is not only influenced by the subjects' object permanence ability. For example, ostensive cues of the human manipulating the target markedly affect dogs' choices. However, the interference between the target's location and the spatial cues of the human hiding the object is still unknown. In a five-location visible displacement task, the experimental groups differed in the hiding route of the experimenter. In the 'direct' condition he moved straight towards the actual location, hid the object and returned to the dog. In the 'indirect' conditions, he additionally walked behind each screen before returning. The two 'indirect' conditions differed from each other in that the human either visited the previously baited locations before (proactive interference) or after (retroactive interference) hiding the object. In the 'indirect' groups, dogs' performance was significantly lower than in the 'direct' group, demonstrating that for dogs, in an ostensive context, spatial cues of the hider are as important as the observed location of the target. Based on their incorrect choices, dogs were most attracted to the previously baited locations that the human visited after hiding the object in the actual trial. This underlines the importance of retroactive interference in multiple choice tasks. PMID- 26869219 TI - Assessment of health in human faces is context-dependent. AB - When making decisions between options, humans are expected to choose the option that returns the highest benefit. In practice, however, adding inferior alternatives to the choice set can alter these decisions. Here we investigated whether decisions over the facial features that people find healthy looking can also be affected by the context in which they see those faces. To do this we examined the effect of choice set on the perception of health of images of faces of light-skinned Caucasian females. We manipulated apparent facial health by changing yellowness of the skin: the healthy faces were moderately yellow and the less healthy faces were either much more yellow or much less yellow. In each experiment, two healthy faces were presented along with a third, less healthy face. When the third face was much more yellow, participants chose the more yellow of the two healthy faces more often as the most healthy. However, when the third face was the least yellow, participants chose the less yellow of the two healthy faces more often. A further experiment confirmed that this result is not due to a generalised preference for an intermediate option. These results extend our understanding of context-dependent decision-making in humans, and suggest that comparative evaluation may be a common feature across many different kinds of choices that humans have to make. PMID- 26869218 TI - The chloride-channel blocker 9-anthracenecarboxylic acid reduces the nonlinear capacitance of prestin-associated charge movement. AB - The basis of the extraordinary sensitivity and frequency selectivity of the cochlea is a chloride-sensitive protein called prestin which can produce an electromechanical response and which resides in the basolateral plasma membrane of outer hair cells (OHCs). The compound 9-anthracenecarboxylic acid (9-AC), an inhibitor of chloride channels, has been found to reduce the electromechanical response of the cochlea and the OHC mechanical impedance. To elucidate these 9-AC effects, the functional electromechanical status of prestin was assayed by measuring the nonlinear capacitance of OHCs from the guinea-pig cochlea and of prestin-transfected human embryonic kidney 293 (HEK 293) cells. Extracellular application of 9-AC caused reversible, dose-dependent and chloride-sensitive reduction in OHC nonlinear charge transfer, Qmax . Prestin-transfected cells also showed reversible reduction in Qmax . For OHCs, intracellular 9-AC application as well as reduced intracellular pH had no detectable effect on the reduction in Qmax by extracellularly applied 9-AC. In the prestin-transfected cells, cytosolic application of 9-AC approximately halved the blocking efficacy of extracellularly applied 9-AC. OHC inside-out patches presented the whole-cell blocking characteristics. Disruption of the cytoskeleton by preventing actin polymerization with latrunculin A or by decoupling of spectrin from actin with diamide did not affect the 9-AC-evoked reduction in Qmax . We conclude that 9-AC acts on the electromechanical transducer principally by interaction with prestin rather than acting via the cytoskeleton, chloride channels or pH. The 9-AC block presents characteristics in common with salicylate, but is almost an order of magnitude faster. 9-AC provides a new tool for elucidating the molecular dynamics of prestin function. PMID- 26869221 TI - A clinical comparison of extraoral panoramic and intraoral radiographic modalities for detecting proximal caries and visualizing open posterior interproximal contacts. AB - OBJECTIVES: The purpose of this study was to compare extraoral panoramic bitewings (BWs) to intraoral photostimulable phosphor (PSP) plate BWs for the detection of proximal surface caries and to establish if there was any difference between extraoral BWs, intraoral BWs and panoramic radiographs in visualizing open posterior interproximal contacts. METHODS: Extraoral panoramic and intraoral BW images were acquired on each of 20 patients, resulting in 489 total non restored, readable surfaces that were evaluated by 4 observers. The ANOVA analysis to determine diagnostic variability between and within each subject was utilized. The surfaces included in the study extended from the distal of each canine to the last posterior contact in each arch with non-readable proximal surfaces excluded (i.e.surfaces where over half the enamel layer was overlapped or where those surfaces were not visible in one or both modalities). RESULTS: The statistical analysis indicated that the overall mean area under the receiver operating characteristic curves across all observers for the intraoral BWs and extraoral panoramic BWs were 0.832 and 0.827, respectively, and the difference of 0.005 was not significant at p = 0.7781. The percentage of non-readable proximal surfaces across the three modalities was 4.1% for intraoral BWs, 18.3% for extraoral panoramic BWs and 51.5% for the standard panoramic images. CONCLUSIONS: The investigators concluded there was no significant difference in posterior proximal surface caries detection between the modalities. Extraoral panoramic BWs were much better than panoramic radiographs in visualizing open posterior interproximal contacts, 81.7% vs 48.5%, but below the 95.9% value for intraoral BWs. PMID- 26869222 TI - Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis. AB - Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the beta subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation. PMID- 26869223 TI - The CD44s splice isoform is a central mediator for invadopodia activity. AB - The ability for tumor cells to spread and metastasize to distant organs requires proteolytic degradation of extracellular matrix (ECM). This activity is mediated by invadopodia, actin-rich membrane protrusions that are enriched for proteases. However, the mechanisms underlying invadopodia activity are not fully understood. Here, we report that a specific CD44 splice isoform, CD44s, is an integral component in invadopodia. We show that CD44s, but not another splice isoform CD44v, is localized in invadopodia. Small hairpin (sh)RNA-mediated depletion of CD44s abolishes invadopodia activity, prevents matrix degradation and decreases tumor cell invasiveness. Our results suggest that CD44s promotes cortactin phosphorylation and recruits MT1-MMP (also known as MMP14) to sites of matrix degradation, which are important activities for invadopodia function. Importantly, we show that depletion of CD44s inhibits breast cancer cell metastasis to the lung in animals. These findings suggest a crucial mechanism underlying the role of the CD44s splice isoform in breast cancer metastasis. PMID- 26869225 TI - The Parkinson's-disease-associated receptor GPR37 undergoes metalloproteinase mediated N-terminal cleavage and ectodomain shedding. AB - The G-protein-coupled receptor 37 ( GPR37) has been implicated in the juvenile form of Parkinson's disease, in dopamine signalling and in the survival of dopaminergic cells in animal models. The structure and function of the receptor, however, have remained enigmatic. Here, we demonstrate that although GPR37 matures and is exported from the endoplasmic reticulum in a normal manner upon heterologous expression in HEK293 and SH-SY5Y cells, its long extracellular N terminus is subject to metalloproteinase-mediated limited proteolysis between E167 and Q168. The proteolytic processing is a rapid and efficient process that occurs constitutively. Moreover, the GPR37 ectodomain is released from cells by shedding, a phenomenon rarely described for GPCRs. Immunofluorescence microscopy further established that although full-length receptors are present in the secretory pathway until the trans-Golgi network, GPR37 is expressed at the cell surface predominantly in the N-terminally truncated form. This notion was verified by flow cytometry and cell surface biotinylation assays. These new findings on the GPR37 N-terminal limited proteolysis may help us to understand the role of this GPCR in the pathophysiology of Parkinson's disease and in neuronal function in general. PMID- 26869224 TI - Suppression of microtubule assembly kinetics by the mitotic protein TPX2. AB - TPX2 is a widely conserved microtubule-associated protein that is required for mitotic spindle formation and function. Previous studies have demonstrated that TPX2 is required for the nucleation of microtubules around chromosomes; however, the molecular mechanism by which TPX2 promotes microtubule nucleation remains a mystery. In this study, we found that TPX2 acts to suppress tubulin subunit off rates during microtubule assembly and disassembly, thus allowing for the support of unprecedentedly slow rates of plus-end microtubule growth, and also leading to a dramatically reduced microtubule shortening rate. These changes in microtubule dynamics can be explained in computational simulations by a moderate increase in tubulin-tubulin bond strength upon TPX2 association with the microtubule lattice, which in turn acts to reduce the departure rate of tubulin subunits from the microtubule ends. Thus, the direct suppression of tubulin subunit off-rates by TPX2 during microtubule growth and shortening could provide a molecular mechanism to explain the nucleation of new microtubules in the presence of TPX2. PMID- 26869226 TI - HDAC6 regulates the dynamics of lytic granules in cytotoxic T lymphocytes. AB - HDAC6 is a tubulin deacetylase involved in many cellular functions related to cytoskeleton dynamics, including cell migration and autophagy. In addition, HDAC6 affects antigen-dependent CD4(+)T cell activation. In this study, we show that HDAC6 contributes to the cytotoxic function of CD8(+)T cells. Immunization studies revealed defective cytotoxic activity in vivo in the absence of HDAC6. Adoptive transfer of wild-type or Hdac6(-/-)CD8(+)T cells to Rag1(-/-)mice demonstrated specific impairment in CD8(+)T cell responses against vaccinia infection. Mechanistically, HDAC6-deficient cytotoxic T lymphocytes (CTLs) showed defective in vitro cytolytic activity related to altered dynamics of lytic granules, inhibited kinesin-1-dynactin-mediated terminal transport of lytic granules to the immune synapse and deficient exocytosis, but not to target cell recognition, T cell receptor (TCR) activation or interferon (IFN)gamma production. Our results establish HDAC6 as an effector of the immune cytotoxic response that acts by affecting the dynamics, transport and secretion of lytic granules by CTLs. PMID- 26869227 TI - CAPS1 effects on intragranular pH and regulation of BDNF release from secretory granules in hippocampal neurons. AB - The secretory protein brain-derived neurotrophic factor (BDNF) is assumed to be a key factor for the induction of synaptic plasticity processes in neurons. However, the molecular mechanisms for activity-dependent release of the protein largely remain elusive. Here, we demonstrate the relevance of the priming factor CAPS1 (also known as CADPS) for the maturation and exocytosis of BDNF-containing secretory granules, as well as for neurotransmitter release from synaptic vesicles. Using live-cell imaging and RNA silencing methods, we show that CAPS1 has a previously unrecognized function in regulating the intragranular pH of BDNF containing secretory granules. Furthermore, our results demonstrate that acute single-cell knockdown of CAPS1 with unaltered expression in neighboring neurons leads to a strong reduction in the number of fusion-competent secretory granules and to a significant decrease of released BDNF following exocytosis in dendrites of CAPS1-deficient neurons. In addition, our results show a reduction in synaptic vesicle turnover after CAPS1 knockdown without affecting the density of active boutons in hippocampal neurons. Thus, our results reveal new functions of endogenous CAPS1 in the BDNF secretory granule life cycle, thereby representing a new mechanism of neuronal plasticity. PMID- 26869229 TI - Patients' Evaluation of Intervention by a Medical Clown Visit or by Viewing a Humorous Film Following In Vitro Fertilization and Embryo Transfer. AB - This study compared responses to an in-person clown visit and a humorous film following in vitro fertilization and embryo transfer. Intervention was a 10 minute clown visit (n = 101) or 10-minute humorous video clip (n = 99). Demographic and fertility-related data and preintervention anxiety scores were collected. Participants completed an Evaluation of Intervention form postintervention. There were no group differences on demographic or fertility related data or anxiety scores. Findings indicate while participants viewed the intervention positively, the clown visit offered a higher degree of satisfaction in more patients than did the film. Median evaluation scores were significantly higher for the clown visit, specifically reducing anxiety level and being more distracting. Both groups reported that the exposure made the clinic experience more pleasant and did not bother them, and most would recommend incorporating the intervention in routine treatment. However, free-text comments clearly expressed greater enthusiasm to the in-person clown intervention than to the film. PMID- 26869228 TI - Mechanistic insights into the inhibition of Sec61-dependent co- and post translational translocation by mycolactone. AB - The virulence factor mycolactone is responsible for the immunosuppression and tissue necrosis that characterise Buruli ulcer, a disease caused by infection with Mycobacterium ulcerans In this study, we confirm that Sec61, the protein conducting channel that coordinates entry of secretory proteins into the endoplasmic reticulum, is a primary target of mycolactone, and characterise the nature of its inhibitory effect. We conclude that mycolactone constrains the ribosome-nascent-chain-Sec61 complex, consistent with its broad-ranging perturbation of the co-translational translocation of classical secretory proteins. In contrast, the effect of mycolactone on the post-translational ribosome-independent translocation of short secretory proteins through the Sec61 complex is dependent on both signal sequence hydrophobicity and the translocation competence of the mature domain. Changes to protease sensitivity strongly suggest that mycolactone acts by inducing a conformational change in the pore-forming Sec61alpha subunit. These findings establish that mycolactone inhibits Sec61 mediated protein translocation and highlight differences between the co- and post translational routes that the Sec61 complex mediates. We propose that mycolactone also provides a useful tool for further delineating the molecular mechanisms of Sec61-dependent protein translocation. PMID- 26869230 TI - Nurses as Leaders in Disaster Preparedness and Response--A Call to Action. AB - PURPOSE: To develop a vision for the future of disaster nursing, identify barriers and facilitators to achieving the vision, and develop recommendations for nursing practice, education, policy, and research. DESIGN AND METHODS: A series of semistructured conference calls were conducted with 14 national subject matter experts to generate relevant concepts regarding national nursing workforce preparedness. An invitational daylong workshop hosted by the Veterans Emergency Management Evaluation Center, U.S. Department of Veterans Affairs, was held in December 2014 to expand and refine these concepts. Workshop participants included 70 nurses, emergency managers, and a broad range of public health professionals. Conference call notes and audiotapes of the workshop were transcribed and thematic analysis conducted to outline a vision for the future of nursing in disaster preparedness and response, and to articulate an agenda for nursing practice, education, policy, and research to achieve that vision. FINDINGS: The group developed a vision for the future of disaster nursing, and identified current barriers and opportunities to advance professional disaster nursing. A broad array of recommendations for nursing practice, education, policy, and research, as well as implementation challenges, are summarized in this article. CONCLUSIONS: This project represents an important step toward enhancing nurses' roles as leaders, educators, responders, policymakers, and researchers in disaster preparedness and response. Nurses and the health and human service organizations that employ them are encouraged to engage in an expansive national dialogue regarding how to best incorporate the vision and recommendations into their individual lives and the organizations for which they work. CLINICAL RELEVANCE: Nurses comprise the largest healthcare workforce, and opportunities exist to strengthen disaster readiness, enhance national surge capacity, and build community resiliency to disasters. PMID- 26869232 TI - Introducing SQUIRE 2.0, the Updated Publication Guidelines for Scientific Reporting of Health Care Improvement Projects: What the Guidelines Mean for Otolaryngologists. PMID- 26869234 TI - Haglund's syndrome. Two case reports. AB - Haglund's syndrome produces posterior impingement of the heel, which is caused by a posterosuperior calcaneal exostosis, known as Haglund's deformity, associated with Achilles tendinitis and retrocalcaneal bursitis. Its pathogenesis is unknown. We report two cases that were diagnosed clinically and confirmed radiographically. One patient was treated conservatively and the other underwent surgery. The diagnosis is based on clinical signs and radiological images, using the measurement of the parallel pitch lines, in a lateral radiograph of the ankle. Initial treatment is usually conservative and includes anti-inflammatory or analgesic agents, physiotherapy and low-heeled, open-heeled shoes. If conservative treatment does not relieve the pain, surgery may be necessary. PMID- 26869235 TI - Glacial lake drainage in Patagonia (13-8 kyr) and response of the adjacent Pacific Ocean. AB - Large freshwater lakes formed in North America and Europe during deglaciation following the Last Glacial Maximum. Rapid drainage of these lakes into the Oceans resulted in abrupt perturbations in climate, including the Younger Dryas and 8.2 kyr cooling events. In the mid-latitudes of the Southern Hemisphere major glacial lakes also formed and drained during deglaciation but little is known about the magnitude, organization and timing of these drainage events and their effect on regional climate. We use 16 new single-grain optically stimulated luminescence (OSL) dates to define three stages of rapid glacial lake drainage in the Lago General Carrera/Lago Buenos Aires and Lago Cohrane/Pueyrredon basins of Patagonia and provide the first assessment of the effects of lake drainage on the Pacific Ocean. Lake drainage occurred between 13 and 8 kyr ago and was initially gradual eastward into the Atlantic, then subsequently reorganized westward into the Pacific as new drainage routes opened up during Patagonian Ice Sheet deglaciation. Coupled ocean-atmosphere model experiments using HadCM3 with an imposed freshwater surface "hosing" to simulate glacial lake drainage suggest that a negative salinity anomaly was advected south around Cape Horn, resulting in brief but significant impacts on coastal ocean vertical mixing and regional climate. PMID- 26869236 TI - Effect on tomato plant and fruit of the application of biopolymer-oregano essential oil coatings. AB - BACKGROUND: Oregano essential oil (EO) was incorporated into film-forming dispersions (FFDs) based on biopolymers (chitosan and/or methylcellulose) at two different concentrations. The effect of the application of the FFDs was evaluated on tomato plants (cultivar Micro-Tom) at three different stages of development, and on pre-harvest and postharvest applications on tomato fruit. RESULTS: The application of the FFDs at '3 Leaves' stage caused phytotoxic problems, which were lethal when the EO was applied without biopolymers. Even though plant growth and development were delayed, the total biomass and the crop yield were not affected by biopolymer-EO treatments. When the FFDs were applied in the 'Fruit' stage the pre-harvest application of FFDs had no negative effects. All FFDs containing EO significantly reduced the respiration rate of tomato fruit and diminished weight loss during storage. Moreover, biopolymer-EO FFDs led to a decrease in the fungal decay of tomato fruit inoculated with Rhizopus stolonifer spores, as compared with non-treated tomato fruit and those coated with FFDs without EO. CONCLUSION: The application of biopolymer-oregano essential oil coatings has been proven to be an effective treatment to control R. stolonifer in tomato fruit. (c) 2016 Society of Chemical Industry. PMID- 26869237 TI - An Incremental Shuttle Wheel Test for Wheelchair Tennis Players. AB - PURPOSE: To determine the relationship between outcomes of the shuttle wheel test (SWT) and peak oxygen uptake (VO2peak) during that test and whether SWT and VO2peak can discriminate between different skill levels of wheelchair tennis players. METHODS: Fifteen wheelchair tennis players performed an SWT on a tennis court while VO2 was measured continuously. Outcome measures were VO2peak and achieved stage. Relations between outcomes and Dutch wheelchair tennis ranking were calculated with Spearman correlation. Independent t tests were used to test for differences between national and international players. RESULTS: Moderate correlations were found between VO2peak and SWT outcome (r = .40-.47). The tennis ranking correlated weakly with VO2peak (r = -.35) and strongly with SWT outcome (r = -.80). A significant difference was found between national and international players for achieved stage (P = .027) and VO2peak (P = .027). CONCLUSIONS: The SWT outcome only explained a small part of the variance in VO2peak among players, so it cannot be considered a valid test for aerobic capacity. However, SWT outcomes are related to the skill level of the player and give a good indication of the overall peak wheelchair performance. PMID- 26869233 TI - Mechanism of ciliary disassembly. AB - As motile organelles and sensors, cilia play pivotal roles in cell physiology, development and organ homeostasis. Ciliary defects are associated with a class of cilia-related diseases or developmental disorders, termed ciliopathies. Even though the presence of cilia is required for diverse functions, cilia can be removed through ciliary shortening or resorption that necessitates disassembly of the cilium, which occurs normally during cell cycle progression, cell differentiation and in response to cellular stress. The functional significance of ciliary resorption is highlighted in controlling the G1-S transition during cell cycle progression. Internal or external cues that trigger ciliary resorption initiate signaling cascades that regulate several downstream events including depolymerization of axonemal microtubules, dynamic changes in actin and the ciliary membrane, regulation of intraflagellar transport and posttranslational modifications of ciliary proteins. To ensure ciliary resorption, both the active disassembly of the cilium and the simultaneous inhibition of ciliary assembly must be coordinately regulated. PMID- 26869238 TI - Microbulbifer rhizosphaerae sp. nov., isolated from the rhizosphere of the halophyte Arthrocnemum macrostachyum. AB - A novel, salt-dependent, non-motile, rod-shaped, Gram-stain-negative and non endospore-forming bacterium, designated strain Cs16bT, was isolated from the rhizosphere of Arthrocnemum macrostachyum, a halophytic plant at the Lebrija marshes (Seville, Spain). Strain Cs16bT was catalase- and oxidase-positive, and able to hydrolyse casein. Growth occurred from 15-40 degrees C, at pH 6.0-10.0 and with 1-6% (w/v) NaCl. Q-8 was identified as the major ubiquinone and the predominant cellular fatty acids were iso-C15:0, iso-C17:1cis8, iso-C11:0 3-OH, iso-C17:0, C17:0 cyclo and iso-C11:0. The polar lipids profile consisted of phosphatidylethanolamine, phosphatidylglycerol, two unknown glycophospholipids, an unknown aminoglycophospholipid, an unknown aminophospholipid and an unknown phospholipid. The 16S rRNA gene of strain Cs16bT showed 98.1%, 97.8%, and 97.6% sequence similarity with Microbulbifer maritimus CIP 108504T, Microbulbifer taiwanensis DSM 24146T and Microbulbifer gwangyangensis JCM 17800T, respectively. Based on the phenotypic and genotypic features, it is concluded that strain Cs16bT represents a novel species of the genus Microbulbifer, for which the name Microbulbifer rhizosphaerae sp. nov. is proposed. The type strain is Cs16bT (=DSM 28920T=CECT 8799T). PMID- 26869239 TI - Antibacterial synergic effect of honey from two stingless bees: Scaptotrigona bipunctata Lepeletier, 1836, and S. postica Latreille, 1807. AB - Several studies have tested antimicrobial activity of combinations of honey and various substances. In this study, we tested a combination of two stingless bee honeys against various bacterial strains. In particular: the antibacterial activity of honeys produced by Scaptotrigona bipunctata (SB) and Scaptotrigona postica (SP) was evaluated against Gram-positive and Gram-negative bacterial strains by agar well diffusion assays, minimum inhibitory concentration (MIC) assessment, construction of growth and viability curves and scanning electron microscopy (SEM). The interaction of the two honeys was also evaluated by the checkerboard assay. Inhibition zones ranged from 8 to 22 mm. The MIC values of the individual honeys ranged from 0.62 to 10% (v v(-1)) and decreased to 1/4 to 1/32 when the honeys were combined. SEM images showed division inhibition and cell wall disruption for the SB and SP honeys, respectively, and these alterations were observed in same field when the SB and SP honeys were combined. This study demonstrated that the natural honeys possess in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug resistant strains. Combination of the SB and SP honeys could lead to the development of new broad-spectrum antimicrobials that have the potential to prevent the emergence of resistant bacterial strains. PMID- 26869240 TI - The relationship between pain and mood following spinal cord injury. AB - OBJECTIVES: To explore the relationship between pain and mood during spinal cord injury rehabilitation, and to discuss clinical implications to optimize rehabilitation outcomes. DESIGN: Repeated measures, retrospective cohort study. SETTING: Tertiary care, spinal cord injury rehabilitation center. PARTICIPANTS: Patients (N = 509) who completed both Needs Assessment Checklist (NAC) 1 and NAC2 between February 2008 and February 2015. INTERVENTIONS: Not applicable. OUTCOME MEASURE: Pain ratings (0-10) and mood scores (0-24) were obtained from the Needs Assessment Checklist (NAC). NAC1 is completed within 4 weeks post-mobilization and NAC2 upon the patient moving to the pre-discharge ward. RESULTS: There were statistically significant improvements in both pain and mood from NAC1 to NAC2. There were significant correlations between pain and mood at both NAC1 and NAC2 (a decrease in pain was associated with an improvement in mood). Individuals who reported that pain interfered with their rehabilitation had higher pain scores and lower mood scores at both NAC1 and NAC2. CONCLUSIONS: Pain and mood evidently interact following spinal cord injury, and the nature of this relationship is complex. The current study provides some support for the bidirectional causality hypothesis, suggesting that pain and mood exert an effect upon each other. It is important to address pain and psychological issues early and together in the post injury phase to optimize rehabilitation outcomes. PMID- 26869241 TI - Is internal jugular vein extensibility associated with indices of fluid responsiveness in ventilated patients? AB - BACKGROUND: Ultrasound of the inferior vena cava provides rapid and non-invasive assessment of fluid responsiveness. We hypothesized that the extensibility of the internal jugular vein (IJV) as well reflects intravascular volume state. We assessed IJV dimensions together with pulse pressure variation (PPV) as dynamic index for fluid responsiveness in mechanically ventilated patients. METHODS: Of 50 patients after cardiac surgery were assessed. Ultrasound of IJV dimensions as well as collection of hemodynamic data were performed in 30 degrees and horizontal (0 degrees ) position, and the ventilator- and position-induced IJV extensibilities (E-IJV) were calculated. RESULTS: Mean ventilator-induced E-IJV in 30 degrees position was 56%, and mean PPV in 30 degrees position was 13.7%. Changing the patient's position from 30 degrees to 0 degrees significantly reduced ventilator-induced E-IJV as well as PPV. Pearson's correlation test revealed significant association between ventilator-induced E-IJV and fluid responsiveness deduced from PPV in 0 degrees position (r = 0.43, P < 0.005). An E-IJV threshold >5% identified patients with significantly elevated PPV values. CONCLUSION: Ultrasound of the IJV and PPV as a dynamic index for fluid responsiveness can be associated under certain defined conditions. Whether or not ultrasound of the IJV can be useful to predict patient intravascular volume state should be further studied using invasive cardiac output monitoring. PMID- 26869242 TI - Neutral, heteroleptic copper(i)-4H-imidazolate complexes: synthesis and characterization of their structural, spectral and redox properties. AB - Facile synthetic access to four novel, neutral, heteroleptic copper(i)-complexes, incorporating 4H-imidazolates as well as the phosphane ligands XantPhos and DPEPhos is reported. The complexes were characterized in the solid state as well as in solution by means of single crystal X-ray diffraction as well as NMR spectroscopy, mass spectrometry and elemental analysis. The copper(i)-4H imidazolate complexes show a broad intense absorption that spans almost the entire visible range. TD-DFT calculations revealed the charge transfer character of the underlying transitions. NMR as well as electrochemical investigations and UV-Vis absorption suggest a polarization of the complexes with the negative charge pushed towards the 4H-imidazolate moiety. PMID- 26869243 TI - Effect of weight loss on operational lung volumes and oxygen cost of breathing in obese women. AB - BACKGROUND: The effects of moderate weight loss on operational lung volumes during exercise and the oxygen (O2) cost of breathing are unknown in obese women but could have important implications regarding exercise endurance. METHODS: In 29 obese women (33+/-8 years, 97+/-14 kg, body mass index: 36+/-4 kg m(-2), body fat: 45.6+/-4.5%; means+/-s.d.), body composition, fat distribution (by magnetic resonance imaging), pulmonary function, operational lung volumes during exercise and the O2 cost of breathing during eucapnic voluntary hyperpnea (([Vdot ]O2) vs ([Vdot ]E) slope) were studied before and after a 12-week diet and resistance exercise weight loss program. RESULTS: Participants lost 7.5+/-3.1 kg or ~8% of body weight (P<0.001), but fat distribution remained unchanged. After weight loss, lung volume subdivisions at rest were increased (P<0.05) and were moderately associated (P<0.05) with changes in weight. End-expiratory lung volume (percentage of total lung capacity) increased at rest and during constant load exercise (P<0.05). O2 cost of breathing was reduced by 16% (2.52+/-1.02-2.11+/ 0.72 ml l(-1); P=0.003). As a result, O2 uptake of the respiratory muscles ([Vdot ]O2Resp), estimated as the product of O2 cost of breathing and exercise ([Vdot ]E) during cycling at 60 W, was significantly reduced by 27+/-31 ml (P<0.001), accounting for 46% of the reduction in total body ([Vdot ]O2) during cycling at 60 W. CONCLUSIONS: Moderate weight loss yields important improvements in respiratory function at rest and during submaximal exercise in otherwise healthy obese women. These changes in breathing load could have positive effects on the exercise endurance and adherence to physical activity. PMID- 26869244 TI - Effect of low-glycemic-sugar-sweetened beverages on glucose metabolism and macronutrient oxidation in healthy men. AB - BACKGROUND/OBJECTIVES: Sugar-sweetened-beverages (SSB) provide high amounts of rapidly absorbable sugar and have been shown to impair insulin sensitivity and promote weight gain. We hypothesized that when compared with high-glycemic index (GI) SSB low-GI SSB lead to lower insulin secretion and thus an improved preservation of insulin sensitivity and fat oxidation during an inactive phase. SUBJECTS/METHODS: In a controlled cross-over dietary intervention 13 healthy men (age: 23.7+/-2.2 years, body mass index: 23.6+/-1.9 kg m(-)(2)) consumed low-GI (isomaltulose) or high-GI (75% maltodextrin+25% sucrose, adapted for sweetness) SSBs providing 20% of energy requirement for 7 days. During this phase, participant's habitual high physical activity (11 375+/-3124 steps per day) was reduced (2363+/-900 steps per day). The provided ad libitum diet comprised 55% CHO, 30% fat and 15% protein. Glycemic and insulinemic responses were assessed: Day-long (7-day continuous interstitial glucose monitoring, 24-h-urinary c peptide excretion), during meal test (37 g isomaltulose vs 28 g maltodextrin+9g sucrose) and measures of insulin sensitivity (basal: homeostasis model assessment of insulin resistance (HOMA-IR), postprandial: Matsuda-ISI). Macronutrient oxidation was assessed by non-protein respiratory quotient (npRQ) in the fasted state (npRQfasting) and postprandial as the area under the npRQ-curve during meal test (npRQtAUC-meal). RESULTS: Day-long glycemia was lower with low-GI compared with high-GI SSB (-5%, P<0.05). Low-GI SSB led to lower insulin secretion during meal test (-28%, P<0.01) and throughout the day (-31%, P<0.01), whereas postprandial glucose levels did not differ between low-GI and high-GI SSBs. Insulin sensitivity deteriorated on inactivity with both SSBs, but was better preserved with low-GI isomaltulose compared with high-GI maltodextrin-sucrose (DeltaHOMA-IR: +0.37+/-0.52 vs +0.85+/-0.86; DeltaMatsuda-ISI: -5.1+/-5.5 vs 9.6+/-5.1, both P<0.05). Both, fasting and postprandial fat oxidation declined on inactivity, with no difference between high-GI and low-GI SSBs. CONCLUSIONS: Compared with high-GI SSB, 7-day consumption of beverages sweetened with low-GI isomaltulose had beneficial effects on inactivity-induced impairment of glucose metabolism without effecting fuel selection. PMID- 26869245 TI - The Role of Trait Anxiety and Preoccupation With Reading Disabilities of Children and Their Mothers in Predicting Children's Reading Comprehension. AB - This study investigated the relationship between reading comprehension (RC), trait anxiety, and preoccupation with reading disability (RD) in 88 school children in Grades 3 through 5 and in their mothers. Children's trait anxiety had a significant direct negative relationship with RC and also mediated the association between preoccupation with RD and RC. Mothers' preoccupation with their children's RDs had a direct negative association with their children's RC. This association was also mediated through children's trait anxiety. No association was found between mothers' trait anxiety and children's RC. In a final model, RC was explained significantly by children's word reading fluency and trait anxiety as well as by their mothers' preoccupation with their children's RDs. This study extends our understanding of multicomponential models of RC by shedding light on the significant role played by anxiety- and preoccupation-related factors involving both children with RDs and their mothers. PMID- 26869246 TI - Divergent Outcomes in Cognitive-Behavioral Therapy and Pharmacotherapy for Adult Depression. AB - OBJECTIVE: Although the average depressed patient benefits moderately from cognitive-behavioral therapy (CBT) or pharmacotherapy, some experience divergent outcomes. The authors tested frequencies, predictors, and moderators of negative and unusually positive outcomes. METHOD: Sixteen randomized clinical trials comparing CBT and pharmacotherapy for unipolar depression in 1,700 patients provided individual pre- and posttreatment scores on the Hamilton Depression Rating Scale (HAM-D) and/or Beck Depression Inventory (BDI). The authors examined demographic and clinical predictors and treatment moderators of any deterioration (increase >=1 HAM-D or BDI point), reliable deterioration (increase >=8 HAM-D or >=9 BDI points), extreme nonresponse (posttreatment HAM-D score >=21 or BDI score >=31), superior improvement (HAM-D or BDI decrease >=95%), and superior response (posttreatment HAM-D or BDI score of 0) using multilevel models. RESULTS: About 5%-7% of patients showed any deterioration, 1% reliable deterioration, 4%-5% extreme nonresponse, 6%-10% superior improvement, and 4%-5% superior response. Superior improvement on the HAM-D only (odds ratio=1.67) and attrition (odds ratio=1.67) were more frequent in pharmacotherapy than in CBT. Patients with deterioration or superior response had lower pretreatment symptom levels, whereas patients with extreme nonresponse or superior improvement had higher levels. CONCLUSIONS: Deterioration and extreme nonresponse and, similarly, superior improvement and superior response, both occur infrequently in randomized clinical trials comparing CBT and pharmacotherapy for depression. Pretreatment symptom levels help forecast negative and unusually positive outcomes but do not guide selection of CBT versus pharmacotherapy. Pharmacotherapy may produce clinician rated superior improvement and attrition more frequently than does CBT. PMID- 26869247 TI - Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo Controlled Trial. AB - OBJECTIVE: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a MU- and kappa-opioid partial agonist, buprenorphine, and a MU-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression. METHOD: A multicenter, randomized, double-blind, placebo-controlled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions severity scale (CGI-S). RESULTS: Compared with the placebo group, there were significantly greater improvements in the 2/2 dosage group across the three depression outcome measures (HAM-D: -2.8, 95% CI=-5.1, -0.6; MADRS: -4.9, 95% CI=-8.2, -1.6; CGI-S: -0.5, 95% CI=-0.9, -0.1). There was also evidence of improvement in the 8/8 dosage group, although it did not achieve statistical significance. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation. CONCLUSIONS: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants. PMID- 26869248 TI - Fluidity of the Subsyndromal Phenomenology of Borderline Personality Disorder Over 16 Years of Prospective Follow-Up. AB - OBJECTIVE: The purpose of this study was to determine the cumulative rates of 2- and 4-year remission, and the recurrences that follow them, of 24 symptoms of borderline personality disorder over 16 years of prospective follow-up. METHOD: A total of 290 inpatients meeting rigorous criteria for borderline personality disorder and 72 axis II comparison subjects were assessed during their index admission using a series of semistructured diagnostic interviews. The same instruments were readministered at eight contiguous 2-year time periods. RESULTS: The 12 acute symptoms (e.g., self-mutilation, help-seeking suicide attempts) of borderline personality disorder were more likely to remit for a period of 2 years and for a period of 4 years than the 12 temperamental symptoms (e.g., chronic anger/frequent angry acts, intolerance of aloneness) of this disorder. They were also less likely to recur after a remission lasting 2 years or a remission lasting 4 years. CONCLUSIONS: Taken together, the symptoms of borderline personality disorder are quite fluid, with remissions and recurrences being common. However, the more clinically urgent acute symptoms of borderline personality disorder seem to have a better prognosis than the less turbulent temperamental symptoms of the disorder. PMID- 26869249 TI - Applying principles from the game theory to acute stroke care: Learning from the prisoner's dilemma, stag-hunt, and other strategies. AB - BACKGROUND: Acute stroke care represents a challenge for decision makers. Decisions based on erroneous assessments may generate false expectations of patients and their family members, and potentially inappropriate medical advice. Game theory is the analysis of interactions between individuals to study how conflict and cooperation affect our decisions. AIMS: We reviewed principles of game theory that could be applied to medical decisions under uncertainty. SUMMARY: Medical decisions in acute stroke care are usually made under constrains: short period of time, with imperfect clinical information, limit understanding about patients and families' values and beliefs. Game theory brings some strategies to help us manage complex medical situations under uncertainty. For example, it offers a different perspective by encouraging the consideration of different alternatives through the understanding of patients' preferences and the careful evaluation of cognitive distortions when applying 'real-world' data. The stag-hunt game teaches us the importance of trust to strength cooperation for a successful patient-physician interaction that is beyond a good or poor clinical outcome. CONCLUSIONS: The application of game theory to stroke care may improve our understanding of complex medical situations and help clinicians make practical decisions under uncertainty. PMID- 26869250 TI - Associations of Apelin, Visfatin, and Urinary 8-Isoprostane With Severe Hypertension in African Americans: The MH-GRID Study. AB - BACKGROUND: Apelin is an adipokine directly associated with adiposity, insulin resistance, and decreased blood pressure. Urinary 8-isoprostane is a marker of chronic oxidative endothelial stress. Visfatin, an adipokine that acts by binding and activating the insulin receptor, has been associated with hypertension. As severe hypertension (SH) is highly prevalent among African Americans (AA), we aimed to assess the association of these biomarkers with SH status. METHODS: A sample of 250 AA participants (134 normotensive controls and 116 with SH (including 98 treatment controlled, SCH: severe controlled hypertension, and 18 treatment resistant, SRH: severe resistant hypertension)) from the Minority Health Genomics and Translational Research Bio-Repository Database (MH-GRID) in metro Atlanta had blood analyzed for apelin and visfatin and urine for 8 isoprostane. T-tests, sex-specific age-adjusted correlation coefficients, and multivariable logistic regression models were used to assess the association of biomarkers with hypertensive status. RESULTS: Levels of apelin and 8-isoprostane were not statistically different between controls and SCH or SRH. Statistically significant differences were present in levels of visfatin between controls (1.03+/-0.84 pg/ml), SCH (1.34+/-1.14 pg/ml), and SRH (1.59+/-0.85 pg/ml). After multivariable adjustment, categorization in the middle 2 quartiles of urinary 8 isoprostane were associated with SH. In similar models, categorization into the highest quartile of visfatin was associated with SH (odds ratio = 2.80; 95% confidence interval: 1.02-7.02). A continuous association of visfatin with SH was present. CONCLUSION: In our community sample of AA, there were increased odds of SH with increased levels of urinary 8-isoprostane and visfatin, but not with apelin. PMID- 26869257 TI - Accelerating Lead Compound Optimization. AB - Chemists at The Scripps Research Institute in La Jolla, CA, and Pfizer's La Jolla Laboratories have devised a new way to rapidly synthesize strained-ring structures, which are increasingly favored to optimize potential drugs. With this method, strain-release amination, Pfizer researchers were able to produce sufficient quantities of a particular structure they needed to evaluate a promising cancer drug candidate. PMID- 26869251 TI - Psychosocial Correlates of Nocturnal Blood Pressure Dipping in African Americans: The Jackson Heart Study. AB - BACKGROUND: African Americans exhibit a lower degree of nocturnal blood pressure (BP) dipping compared with Whites, but the reasons for reduced BP dipping in this group are not fully understood. The aim of this study was to identify psychosocial factors associated with BP dipping in a population-based cohort of African Americans. METHODS: This cross-sectional study included 668 Jackson Heart Study (JHS) participants with valid 24-hour ambulatory BP data and complete data on psychosocial factors of interest including stress, negative emotions, and psychosocial resources (e.g., perceived support). The association of each psychosocial factor with BP dipping percentage and nondipping status (defined as <10% BP dipping) was assessed using linear and Poisson regression models, respectively, with progressive adjustment for demographic, socioeconomic, biomedical, and behavioral factors. RESULTS: The prevalence of nondipping was 64%. Higher depressive symptoms, higher hostility, and lower perceived social support were associated with a lower BP dipping percentage in unadjusted models and after adjustment for age, sex, body mass index, and mean 24-hour systolic BP (P < 0.05). Only perceived support was associated with BP dipping percentage in fully adjusted models. Also, after full multivariable adjustment, the prevalence ratio for nondipping BP associated with 1 SD (7.1 unit) increase in perceived support was 0.93 (95% CI: 0.88-0.99). No other psychosocial factors were associated with nondipping status. CONCLUSIONS: Lower perceived support was associated with reduced BP dipping in this study. The role of social support as a potentially modifiable determinant of nocturnal BP dipping warrants further investigation. PMID- 26869252 TI - Use of evidence-based therapy and survival in heart failure in Sweden 2003-2012. AB - AIMS: In heart failure with reduced ejection fraction, drug and device therapy improve survival. We studied contemporary trends in utilization of evidence-based therapy and associated survival. METHODS AND RESULTS: We studied 5908 patients with NYHA class II-IV heart failure, EF <30%, and duration of heart failure >=6 months registered in the Swedish Heart Failure Registry between 2003 and 2012. Regression using generalized estimation equations was used to examine temporal trends in crude and risk-adjusted rates of utilization of evidence-based heart failure therapy and 30-day, 1-year, and 3-year survival. In 2003 vs. 2012, the risk-adjusted use of therapy and P-values for trends were as follows: renin angiotensin system antagonists, 88% vs. 86% (P = 0.091); beta-blockers, 85% vs. 93% (P = 0.008); mineralocorticoid receptor antagonists, 53% vs. 42% (P < 0.001); CRT, 2.4% vs. 8.2% (P = 0.074); and implantable cardioverter-defibrillators, 4.0% vs. 10.7% (P = 0.004). During the same period, the risk-adjusted 30-day, 1-year, and 3-year survival was 92% vs. 94% (P = 0.532), 81% vs. 77% (P = 0.260), and 58% vs. 54% (P = 0.425), respectively. CONCLUSIONS: In this large nationwide registry, over the last decade the use of evidence-based drug therapy was high and remained stable over time, but, despite an increased use of device therapy, the absolute use was poor. This was associated with an absence of improvement in survival. The improvements in therapy and prognosis over the last generation may be levelling off, and efforts should be directed at improving implementation of evidence-based therapy. PMID- 26869258 TI - Balloon dilation of the Eustachian tube: a tympanometric outcomes analysis. AB - BACKGROUND: Eustachian tube dysfunction (ETD) is a common medical issue, occurring in at least 1% of the adult population. Patients suffering from ET dysfunction typically present with complaints of hearing loss or sensation of pressure or plugged ear, which can lead to impaired quality of life. Over time ETD can result in conductive hearing loss or choleastatoma formation. Effective theraputic options for ET dysfunction are few. Eustachian tube balloon dilation is a novel surgical technique being used to treat ETD. The aim of our study is to objectively measure the success of Eustachian tube balloon dilation by comparing pre and post-operative middle ear pressures using tympanometric testing. METHODS: RA retrospective chart review was preformed on all patients who underwent balloon dilation of the Eustachian tube by authors NC or MB from 2010 to 2014. Pre and post-operative tympanograms were analyzed and categorized based on type (Type A, Type B, Type C). Success was defined by an improvement in tympanogram type: Type B or C to Type A, or Type B to type C. Pre and post-operative tympanograms were further analyzed using middle ear pressure values. Follow-up ranged from 3 to 15 months. RESULTS: Twenty-five ears (18 patients) were included in the study. Overall 36% of ears had improvement in tympanogram type, and 32% had normalization of tympanogram post-operatively. The Jerger tympanogram type improved significantly following the procedure (p = 0.04). Patients also had statistically significant improvement in measured middle ear pressure post operatively (P = 0.003). CONCLUSION: The natural history of Eustachian tube dysfunction is poorly understood, and evidence for current treatments are limited. Eustachian tube balloon dilation is a safe procedure, and produces significant improvement in tympanogram values up to 15 months post-operatively. Further refinement of patient selection and standardization of technique is required to optimize the effect of this therapy. Longterm follow-up data will clarify the persistence of the effect. PMID- 26869259 TI - Involvement of older people in the development of fall detection systems: a scoping review. AB - BACKGROUND: The involvement of users is recommended in the development of health related technologies, in order to address their needs and preferences and to improve the daily usage of these technologies. The objective of this literature review was to identify the nature and extent of research involving older people in the development of fall detection systems. METHODS: A scoping review according to the framework of Arksey and O'Malley was carried out. A key term search was employed in eight relevant databases. Included articles were summarized using a predetermined charting form and subsequently thematically analysed. RESULTS: A total of 53 articles was included. In 49 of the 53 articles, older people were involved in the design and/or testing stages, and in 4 of 53 articles, they were involved in the conceptual or market deployment stages. In 38 of the 53 articles, the main focus of the involvement of older people was technical aspects. In 15 of the 53 articles, the perspectives of the elderly related to the fall detection system under development were determined using focus groups, single interviews or questionnaires. CONCLUSIONS: Until presently, involvement of older people in the development of fall detection systems has focused mainly on technical aspects. Little attention has been given to the specific needs and views of older people in the context of fall detection system development and usage. PMID- 26869260 TI - Interstitial telomeric sites and Robertsonian translocations in species of Ipheion and Nothoscordum (Amaryllidaceae). AB - The genera Nothoscordum and Ipheion (Allioideae, Amaryllidaceae) are cytologically characterized by a dysploid series with variable numbers of metacentric and acrocentric chromosomes typical of karyotypes rearranged by Robertsonian translocations (RT). Since they have large chromosomes, low diploid numbers, and possess two telomeric motifs [the vertebrate-type (TTAGGG) n and the Arabidopsis-type (TTTAGGG) n ] they are suitable for investigating the occurrence and possible role of interstitial telomeric sites (ITS) associated with RT. We analyzed the distributions of telomeric sites in 12 species of Nothoscordum and Ipheion and found that both telomeric probes colocalized in all chromosome termini. Cloning and sequencing PCR products obtained using both telomeric primers simultaneously revealed long stretches of (TTAGGG) n and (TTTAGGG) n sequences together with degenerated telomeric sequences. Most acrocentric chromosomes have a 45S rDNA site at the terminal region of the short arms adjacent to the most distal telomeric sites. Telomeric signals were found at all chromosome ends, but ITS were also detected in a few proximal and subterminal regions in some Nothoscordum species. Although RT are common in this group of plants, our findings suggest that proximal positioning of telomeric motifs are not necessarily related to that kind of rearrangement. Rather, transposition of telomeric sequences followed by amplification, could better explain the presence of (TTAGGG) n and (TTTAGGG) n repeats at those sites. Furthermore, a few small interstitial sites found in some Nothoscordum species indicate that dispersion of these sequences was not restricted to the proximal region. PMID- 26869261 TI - Identification and functional characterization of the pepper CaDRT1 gene involved in the ABA-mediated drought stress response. AB - Plants are constantly challenged by various environmental stresses, including high salinity and drought, and they have evolved defense mechanisms to counteract the deleterious effects of these stresses. The plant hormone abscisic acid (ABA) regulates plant growth and developmental processes and mediates abiotic stress responses. Here, we identified the Capsicum annuum DRought Tolerance 1 (CaDRT1) gene from pepper leaves treated with ABA. CaDRT1 was strongly expressed in pepper leaves in response to environmental stresses and after ABA treatment, suggesting that the CaDRT1 protein functions in the abiotic stress response. Knockdown expression of CaDRT1 via virus-induced gene silencing resulted in a high level of drought susceptibility, and this was characterized by increased transpirational water loss via decreased stomatal closure. CaDRT1-overexpressing (OX) Arabidopsis plants exhibited an ABA-hypersensitive phenotype during the germinative, seedling, and adult stages. Additionally, these CaDRT1-OX plants exhibited a drought-tolerant phenotype characterized by low levels of transpirational water loss, high leaf temperatures, increased stomatal closure, and enhanced expression levels of drought-responsive genes. Taken together, our results suggest that CaDRT1 is a positive regulator of the ABA-mediated drought stress response. PMID- 26869262 TI - A wheat superoxide dismutase gene TaSOD2 enhances salt resistance through modulating redox homeostasis by promoting NADPH oxidase activity. AB - Superoxide dismutase (SOD) is believed to enhance abiotic stress resistance by converting superoxide radical (O2 (-)) to H2O2 to lower ROS level and maintain redox homeostasis. ROS level is controlled via biphasic machinery of ROS production and scavenging. However, whether the role of SOD in abiotic stress resistance is achieved through influencing the biophasic machinery is not well documented. Here, we identified a wheat copper-zinc (Cu/Zn) SOD gene, TaSOD2, who was responsive to NaCl and H2O2. TaSOD2 overexpression in wheat and Arabidopsis elevated SOD activities, and enhanced the resistance to salt and oxidative stress. TaSOD2 overexpression reduced H2O2 level but accelerated O2 (-) accumulation. Further, it improved the activities of H2O2 metabolic enzymes, elevated the activity of O2 (-) producer NADPH oxidase (NOX), and promoted the transcription of NOX encoding genes. The inhibition of NOX activity and the mutation of NOX encoding genes both abolished the salt resistance of TaSOD2 overexpression lines. These data indicate that Cu/Zn SOD enhances salt resistance, which is accomplished through modulating redox homeostasis via promoting NOX activity. PMID- 26869266 TI - Solitary Infantile Myofibroma of Left Ethmoid Sinus With Intracranial Extension. PMID- 26869263 TI - Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation. AB - Motivated reward-seeking behaviours are governed by dopaminergic ventral tegmental area projections to the nucleus accumbens. In addition to dopamine, these mesoaccumbal terminals co-release other neurotransmitters including glutamate and GABA, whose roles in regulating motivated behaviours are currently being investigated. Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation. PMID- 26869265 TI - The accuracy and completeness for receipt of colorectal cancer care using Veterans Health Administration administrative data. AB - BACKGROUND: The National Comprehensive Cancer Network and the American Society of Clinical Oncology have established guidelines for the treatment and surveillance of colorectal cancer (CRC), respectively. Considering these guidelines, an accurate and efficient method is needed to measure receipt of care. METHODS: The accuracy and completeness of Veterans Health Administration (VA) administrative data were assessed by comparing them with data manually abstracted during the Colorectal Cancer Care Collaborative (C4) quality improvement initiative for 618 patients with stage I-III CRC. RESULTS: The VA administrative data contained gender, marital, and birth information for all patients but race information was missing for 62.1% of patients. The percent agreement for demographic variables ranged from 98.1-100%. The kappa statistic for receipt of treatments ranged from 0.21 to 0.60 and there was a 96.9% agreement for the date of surgical resection. The percentage of post-diagnosis surveillance events in C4 also in VA administrative data were 76.0% for colonoscopy, 84.6% for physician visit, and 26.3% for carcinoembryonic antigen (CEA) test. CONCLUSIONS: VA administrative data are accurate and complete for non-race demographic variables, receipt of CRC treatment, colonoscopy, and physician visits; but alternative data sources may be necessary to capture patient race and receipt of CEA tests. PMID- 26869267 TI - Rates of Autism Spectrum Disorder Diagnosis Under the DSM-5 Criteria Compared to DSM-IV-TR Criteria in a Hospital-Based Clinic. AB - BACKGROUND: We aimed to determine whether there was a decrease in the number of children diagnosed on the autism spectrum after the implementation of the new diagnostic criteria as outlined in the Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition published in May 2013. METHOD: We reviewed 1552 charts of children evaluated at the Women and Children's Hospital of Buffalo, Autism Spectrum Disorders Clinic. A comparison was made of children diagnosed with autism spectrum disorder (autism, Asperger disorder, pervasive developmental disorder-not otherwise specified) from 2010 to May 2013 using the Diagnostic and Statistical Manual of Mental Health Disorders Fourth Edition, Text Revision criteria with children diagnosed from June 2013 through June 2015 under the Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition. RESULTS: Using chi(2) analysis, the 2013-2015 rate of autism spectrum disorder diagnosis (39%) was significantly lower (P < 0.01) than the 2010 to May 2013 sample years rate (50%). CONCLUSION: The rate of autism spectrum disorder diagnosis was significantly lower under the recently implemented Diagnostic and Statistical Manual of Mental Health Disorders Fifth Edition criteria. PMID- 26869264 TI - Mesenchymal stem/stromal cells-a key mediator for regeneration after perinatal morbidity? AB - Perinatal complications in both term- and preterm-born infants are a leading cause of neonatal morbidities and mortality. Infants face different challenges in the neonatal intensive care unit with long-term morbidities such as perinatal brain injury and bronchopulmonary dysplasia being particularly devastating. While advances in perinatal medicine have improved our understanding of the pathogenesis, effective therapies to prevent and/or reduce the severity of these disorders are still lacking. The potential of mesenchymal stem/stromal cell (MSC) therapy has emerged during the last two decades, and an increasing effort is conducted to address brain- and lung-related morbidities in neonates at risk. Various studies support the notion that MSCs have protective effects. MSCs are an easy source and may be readily available after birth in a clinical setting. MSCs' mechanisms of action are diverse, including migration and homing, release of growth factors and immunomodulation, and the potential to replace injured cells. Here, we review the pathophysiology of perinatally acquired brain and lung injuries and focus on MSCs as potential candidates for therapeutic strategies summarizing preclinical and clinical evidence. PMID- 26869269 TI - Protecting the properties of monolayer MoS2 on silicon based substrates with an atomically thin buffer. AB - Semiconducting 2D materials, like transition metal dichalcogenides (TMDs), have gained much attention for their potential in opto-electronic devices, valleytronic schemes, and semi-conducting to metallic phase engineering. However, like graphene and other atomically thin materials, they lose key properties when placed on a substrate like silicon, including quenching of photoluminescence, distorted crystalline structure, and rough surface morphology. The ability to protect these properties of monolayer TMDs, such as molybdenum disulfide (MoS2), on standard Si-based substrates, will enable their use in opto-electronic devices and scientific investigations. Here we show that an atomically thin buffer layer of hexagonal-boron nitride (hBN) protects the range of key opto-electronic, structural, and morphological properties of monolayer MoS2 on Si-based substrates. The hBN buffer restores sharp diffraction patterns, improves monolayer flatness by nearly two-orders of magnitude, and causes over an order of magnitude enhancement in photoluminescence, compared to bare Si and SiO2 substrates. Our demonstration provides a way of integrating MoS2 and other 2D monolayers onto standard Si-substrates, thus furthering their technological applications and scientific investigations. PMID- 26869268 TI - Maternal urinary manganese and risk of low birth weight: a case-control study. AB - BACKGROUND: Manganese (Mn) is an essential element for humans, but exposure to high levels has been associated with adverse developmental outcomes. Early epidemiological studies evaluating the effect of Mn on fetal growth are inconsistent. METHODS: We investigated the association between maternal urinary Mn during pregnancy and the risk of low birth weight (LBW). Mn concentrations in maternal urine samples collected before delivery were measured in 816 subjects (204 LBW cases and 612 matched controls) recruited between 2012 and 2014 in Hubei Province, China. RESULTS: The median Mn concentration in maternal urine was 0.69 MUg/g creatinine. Compared to the medium tertile of Mn levels, an increased risk of LBW was observed for the lowest tertile (<=0.30 MUg/g creatinine) [adjusted odds ratio (OR) = 1.28; 95 % confidence interval (CI) = 0.67, 2.45], and a significantly increased risk of LBW was observed for the highest tertile (>=1.16 MUg/g creatinine) [adjusted OR = 2.04; 95 % CI = 1.12, 3.72]. A curvilinear relationship between maternal urinary Mn and risk of LBW was observed, showing that the concentration at 0.43 MUg/g creatinine was the point of inflection. Similar associations were observed among the mothers with female infants and among the younger mothers < 28 years old. However, among the mothers with male infants or the older mothers >= 28 years old, only higher levels of Mn were positively associated with LBW. CONCLUSIONS: Lower or higher levels of maternal urinary Mn are associated with LBW, though only the association of LBW risk and higher levels of Mn was statistically significant. The findings also show that the associations may vary by maternal age and infant sex, but require confirmation in other populations. PMID- 26869271 TI - [Subjective time left in life and precautionary relocation planning in the last half of life]. AB - BACKGROUND: Many people wish to remain in current residence for as long as possible. Nonetheless, they do think about their residential future. For older people the question of where to live must be considered with respect to age related changes and continuity. So far only little research has been focused on the influence of the subjective perception of remaining lifetime until death on plans for the future, for example regarding relocation. OBJECTIVE: This study investigated the influence of the subjective perception of time left to live on relocation planning and its timing in the further course of life. MATERIAL AND METHODS: The data were obtained from a paper-pencil questionnaire including 2156 persons aged 50 years and older (average age 65.5 years, SD = 9.7 years, range 50-94 years, 51.1 % female) who were asked about their wishes and plans for the future, particularly about their relocation considerations and the subjective perception of remaining time until death. RESULTS: Approximately 39 % of the subjects considered relocation in the further course of life. Besides social demographics, current housing and the state of health, the subjective time left in life had a significant influence on the consideration of relocation and its timing in the further course of life. Persons who perceived their time horizon as limited considered relocation later in life (temporizing relocation planning) than persons who perceived themselves to have more time left in life. Their temporal occurrence of precautionary relocation planning is embedded earlier in the course of life. CONCLUSION: Thoughts about the residential future of older people should be considered not only in connection with the content of these wishes but also related to the future time perspective and the timing in the further course of life. This can be of assistance in consultation and decision making situations. PMID- 26869270 TI - [Depression in old age, part 2 : Comorbidity and treatment]. AB - Depression in later life unfavorably impacts on the prognosis of comorbid somatic medical conditions. There are mutually reciprocal risk relationships with several frequently occurring medical conditions, such as diabetes, ischemic heart disease, stroke and Parkinson's disease. A wide range of psychological and psychosocial interventions, drug treatment and other biological interventions are available for treatment, including special interventions for enhancement of effectiveness and therapy resistance. PMID- 26869272 TI - [Mobile dementia counseling as low-threshold assistance for caregiving relatives]. AB - BACKGROUND: Comprehensive and easily accessible information and counseling for people with dementia and their caregivers can improve home care in many ways; however, for various reasons the affected persons rarely seek help and advice. When advice is sought the caregiving situation at home is mostly already in a crisis. The Rhine-Erft district, a rural area in Germany, improved its network of dementia care services by establishing a mobile gerontopsychiatric counseling service with a special focus on dementia. A multiprofessional and interdisciplinary team consisting of professional and voluntary personnel in a specially equipped bus offers free counseling at several public places in the district at least once a month. OBJECTIVES: The project was accompanied and scientifically evaluated by the authors of this article from 2012 to 2015. The German Ministry of Health funded the evaluation. The main objective of the scientific evaluation was to examine how to implement the mobile counseling in order to improve the situation for people with dementia and their informal caregivers. MATERIAL AND METHODS: A mixture of quantitative (e.g. standardized questionnaires) and qualitative (e.g. semi-structured interviews) methods was employed. RESULTS/CONCLUSION: The data show that the mobile counseling service fulfills an important role in the navigation into the healthcare system and contributes to the easing of caregiver burden. In particular, the low threshold of the service proved to be very effective. The mobile counseling service can reach those caregivers who would have sought professional advice too late or not at all. PMID- 26869273 TI - Cytoprotective mechanism of ferulic acid against high glucose-induced oxidative stress in cardiomyocytes and hepatocytes. AB - BACKGROUND: Ferulic acid (FA), a phenolic acid, is a potential therapy for diabetes mellitus. FA has been shown to protect against hepatic and myocardial injury and oxidative stress in obese rats with late-stage diabetes, but the mechanism of the antioxidative activity of FA is still unclear. OBJECTIVE: The aim of this study was to elucidate whether FA can prevent damage to cardiomyocytes and hepatocytes caused by high glucose (HG)-induced oxidative stress and whether the protection effects of FA on these cells are related to the Keap1-Nrf2-ARE signaling pathways. DESIGN: Cells were divided into four groups: a control group (cultured with normal medium), an HG group (medium containing 80 mmol/L glucose), an FA+HG group (medium containing 80 mmol/L glucose and 1, 5, or 10 ug/mL FA), and a dimethylbiguanide (DMBG)+HG group (medium containing 80 mmol/L glucose and 50 ug/mL DMBG). RESULTS: FA treatment significantly increased cell viability and significantly decreased cell apoptosis compared with the HG treated group. Moreover, FA down-regulated the expression of Keap1 protein and up regulated the expression of Nrf2 protein and gene transcription of HO-1 and glutathione S-transferase (GST) in a dose-dependent manner. CONCLUSION: FA alleviated the HG-induced oxidative stress and decreased cell apoptosis in hepatocytes and cardiomyocytes. These effects were associated with the Keap1-Nrf2 ARE signaling pathway. PMID- 26869274 TI - Ontogeny of head and caudal fin shape of an apex marine predator: The tiger shark (Galeocerdo cuvier). AB - How morphology changes with size can have profound effects on the life history and ecology of an animal. For apex predators that can impact higher level ecosystem processes, such changes may have consequences for other species. Tiger sharks (Galeocerdo cuvier) are an apex predator in tropical seas, and, as adults, are highly migratory. However, little is known about ontogenetic changes in their body form, especially in relation to two aspects of shape that influence locomotion (caudal fin) and feeding (head shape). We captured digital images of the heads and caudal fins of live tiger sharks from Southern Florida and the Bahamas ranging in body size (hence age), and quantified shape of each using elliptical Fourier analysis. This revealed changes in the shape of the head and caudal fin of tiger sharks across ontogeny. Smaller juvenile tiger sharks show an asymmetrical tail with the dorsal (upper) lobe being substantially larger than the ventral (lower) lobe, and transition to more symmetrical tail in larger adults, although the upper lobe remains relatively larger in adults. The heads of juvenile tiger sharks are more conical, which transition to relatively broader heads over ontogeny. We interpret these changes as a result of two ecological transitions. First, adult tiger sharks can undertake extensive migrations and a more symmetrical tail could be more efficient for swimming longer distances, although we did not test this possibility. Second, adult tiger sharks expand their diet to consume larger and more diverse prey with age (turtles, mammals, and elasmobranchs), which requires substantially greater bite area and force to process. In contrast, juvenile tiger sharks consume smaller prey, such as fishes, crustaceans, and invertebrates. Our data reveal significant morphological shifts in an apex predator, which could have effects for other species that tiger sharks consume and interact with. PMID- 26869276 TI - Updating our approach to the difficult and failed airway: time to "stop and think". PMID- 26869277 TI - Job shortages in anesthesia: a pro or con? PMID- 26869275 TI - A synergistic blocking effect of Mg2+ and spermine on the inward rectifier K+ (Kir2.1) channel pore. AB - Inward rectifier K(+) channels (Kir2.1) exhibit an extraordinary rectifying feature in the current-voltage relationship. We have previously showed that the bundle-crossing region of the transmembrane domain constitutes the crucial segment responsible for the polyamine block. In this study, we demonstrated that the major blocking effect of intracellular Mg(2+) on Kir2.1 channels is also closely correlated with K(+) current flow, and the coupled movements of Mg(2+) and K(+) seem to happen in the same flux-coupling segment of the pore as polyamines. With a preponderant outward K(+) flow, intracellular Mg(2+) would also be pushed to and thus stay at the outermost site of a flux-coupling segment in the bundle-crossing region of Kir2.1 channels to block the pore, although with a much lower apparent affinity than spermine (SPM). However, in contrast to the evident possibilities of outward exit of SPM through the channel pore especially during strong membrane depolarization, intracellular Mg(2+) does not seem to traverse the Kir2.1 channel pore in any case. Intracellular Mg(2+) and SPM therefore may have a synergistic action on the pore-blocking effect, presumably via prohibition of the outward exit of the higher-affinity blocking SPM by the lower-affinity Mg(2+). PMID- 26869279 TI - Genome organization and host range of a Brazilian isolate of johnsongrass mosaic virus. AB - This work reports the complete genome sequence, production of a polyclonal antiserum, and host range of a Brazilian strain of johnsongrass mosaic virus (JGMV) found infecting Panicum maximum in the state of Sao Paulo, Brazil. The complete genome sequence of this potyvirus, comprising 9874 nucleotides, showed 82 % amino acid sequence identity in the polyprotein to that of an isolate of JGMV from Australia. The experimental host range of this virus included mainly fodder species. Cultivated species such as rice, oats, sugarcane, rye, corn and wheat were not infected, suggesting that current isolates of this potyvirus do not represent a threat to these crops in Brazil. PMID- 26869278 TI - Interleukin-6 trans-signalling induces vascular endothelial growth factor synthesis partly via Janus kinases-STAT3 pathway in human mesothelial cells. AB - AIMS: Interleukin-6 (IL-6) is a vital inflammatory factor in the peritoneal cavity of peritoneal dialysis (PD) patients. Because intraperitoneal inflammation is closely associated with angiogenesis, we sought to explore the effect of IL-6 on vascular endothelial growth factor (VEGF) synthesis and its transduction pathway in mesothelial cells. METHODS: Human mesothelial cells (Met-5A) were incubated with different concentrations of glucose and mannitol, and the effect of glucose and mannitol on the expression of IL-6 was determined. Then, the cells were stimulated by IL-6 with or without two soluble receptors of IL-6 (sIL-6R or sgp130), and VEGF synthesis was detected. Finally, the cells were incubated with IL-6/sIL-6R combined with or without the inhibitor of Janus kinases (JAK) AG490. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) and its intracellular translocation were examined. RESULTS: 1. High glucose and mannitol could upregulate IL-6 mRNA expression and IL-6 secretion in mesothelial cells significantly, and there was no difference of its effect between high glucose and mannitol. 2. Met-5A was a cell line with a single IL-6 receptor. The IL-6/sIL-6R complex induced VEGF synthesis of mesothelial cells, which was alleviated by sgp130 or AG490. IL-6 trans-signalling could induce the phosphorylation of STAT3, which is recruited to the cellular nucleus of Met-5A cells. CONCLUSION: The present study might provide evidence that high glucose upregulates IL-6 synthesis in Met-5A cells, to some extent, depending on its osmolality and that IL-6 trans-signalling could induce VEGF synthesis partly dependent on the JAK/STAT3 pathway. PMID- 26869280 TI - Comparative dose response using the intravenous versus enteral route of administration for potassium replenishment. AB - OBJECTIVE: To compare the change in potassium concentration (dose-response) using the intravenous versus enteral route for potassium replenishment. RESEARCH METHODOLOGY/DESIGN: Cross-sectional analysis of individual potassium chloride doses with resulting changes in plasma potassium concentrations in intensive care patients. Potassium chloride was administered according to potassium replenishment protocols. For inclusion, doses were required to have pre- and post dose plasma potassium concentrations obtained within 8hours of administration. SETTING: Medical and surgical intensive care units of a United States Veterans Affairs Medical Center. MAIN OUTCOME MEASURES: The primary outcome was the dose response slope for intravenous versus enteral potassium administration as estimated by linear regression analysis. Multivariable linear regression was employed to adjust for potential confounders. RESULTS: The sample had 278 potassium chloride doses administered to 142 patients. The potassium concentration change per 20mmol of potassium chloride was similar for intravenous and enteral routes, 0.25mmol/L (95% confidence interval 0.16-0.33) versus 0.27mmol/L (0.15-0.39) respectively (p=0.73). Multivariable linear regression did not alter results. The success of achieving a minimum potassium concentration defined by the specific protocol was similar for intravenous (61%) and enteral (59%) administration. Overall, 77% of potassium chloride doses were administered at a time when patients were eligible to receive an enteral dosage form. CONCLUSION: The enteral route was as effective as the intravenous route in increasing the plasma potassium concentration. The enteral route was widely available for potassium replenishment. Despite enteral route availability and the well-known reliability of potassium chloride absorption, the majority of doses were administered intravenously. PMID- 26869281 TI - WNT-activated medulloblastoma with melanotic and myogenic differentiation: Report of a rare case. AB - Medulloblastoma (MB) with melanotic and myogenic differentiation, previously known as melanotic medullomyoblastoma, is an extremely rare histological variant of MB showing melanocytic as well as skeletal muscle differentiation. Only 10 cases of this rare tumor have been reported in the literature to date. We report this case of a 2-year-old male child who presented with a midline cerebellar mass, which on histopathological examination showed classic MB intermixed with cells containing melanin pigment, along with rhabdomyoblasts, spindle cells and occasional strap cells, which corresponded to WNT subgroup on molecular classification. The cell of origin of this MB variant is likely to be neural crest-derived stem cells which are capable of multilineage differentiation. Significant findings from previous reports and important differential diagnoses are discussed. Documentation of these tumors is important to characterize the clinical behaviour and to identify distinct genetic features, if any. PMID- 26869282 TI - Estimating the impact of various pathway parameters on tenderness, flavour and juiciness of pork using Monte Carlo simulation methods. AB - Monte Carlo simulation was investigated as a potential methodology to estimate sensory tenderness, flavour and juiciness scores of pork following the implementation of key pathway interventions known to influence eating quality. Correction factors were established using mean data from published studies investigating key production, processing and cooking parameters. Probability distributions of correction factors were developed for single pathway parameters only, due to lack of interaction data. Except for moisture infusion, ageing period, aitchbone hanging and cooking pork to an internal temperature of >74 degrees C, only small shifts in the mean of the probability distributions of correction factors were observed for the majority of pathway parameters investigated in this study. Output distributions of sensory scores, generated from Monte Carlo simulations of input distributions of correction factors and for individual pigs, indicated that this methodology may be useful in estimating both the shift and variability in pork eating traits when different pathway interventions are applied. PMID- 26869283 TI - Consented Autopsy and the Middle-East. AB - Consented autopsy is almost non-existent in the Middle-East where established social and cultural beliefs regarding the procedure might discourage family members from requesting a consented autopsy. Evidence suggests that new information is obtained from consented autopsies. It would not be in the best interest of medicine if social and cultural misconceptions succeed in erasing the existence of consented autopsies entirely. PMID- 26869286 TI - Whole-Body and Local Muscle Vibration Immediately Improve Quadriceps Function in Individuals With Anterior Cruciate Ligament Reconstruction. AB - OBJECTIVE: To determine the immediate effects of a single session of whole-body vibration (WBV) and local muscle vibration (LMV) on quadriceps function in individuals with anterior cruciate ligament reconstruction (ACLR). DESIGN: Singe blind, randomized crossover trial. SETTING: Research laboratory. PARTICIPANTS: Population-based sample of individuals with ACLR (N=20; mean age +/- SD, 21.1+/ 1.2y; mean mass +/- SD, 68.3+/-14.9kg; mean time +/- SD since ACLR, 50.7+/ 21.3mo; 14 women; 16 patellar tendon autografts, 3 hamstring autografts, 1 allograft). INTERVENTIONS: Participants performed isometric squats while being exposed to WBV, LMV, or no vibration (control). Interventions were delivered in a randomized order during separate visits separated by 1 week. MAIN OUTCOME MEASURES: Quadriceps active motor threshold (AMT), motor-evoked potential (MEP) amplitude, Hoffmann reflex (H-reflex) amplitude, peak torque (PT), rate of torque development (RTD), electromyographic amplitude, and central activation ratio (CAR) were assessed before and immediately after a WBV, LMV, or control intervention. RESULTS: There was an increase in CAR (+4.9%, P=.001) and electromyographic amplitude (+16.2%, P=.002), and a reduction in AMT (-3.1%, P<.001) after WBV, and an increase in CAR (+2.7%, P=.001) and a reduction in AMT (-2.9%, P<.001) after LMV. No effect was observed after WBV or LMV in H-reflex, RTD, or MEP amplitude. AMT (-3.7%, P<.001), CAR (+5.7%, P=.005), PT (+.31Nm/kg, P=.004), and electromyographic amplitude (P=.002) in the WBV condition differed from the control condition postapplication. AMT (-3.0% P=.002), CAR (+3.6%, P=.005), and PT (+.30Nm/kg, P=.002) in the LMV condition differed from the control condition postapplication. No differences were observed between WBV and LMV postapplication in any measurement. CONCLUSIONS: WBV and LMV acutely improved quadriceps function and could be useful modalities for restoring quadriceps strength in individuals with knee pathologies. PMID- 26869285 TI - Machine learning-based classification of diffuse large B-cell lymphoma patients by eight gene expression profiles. AB - Gene expression profiling (GEP) had divided the diffuse large B-cell lymphoma (DLBCL) into molecular subgroups: germinal center B-cell like (GCB), activated B cell like (ABC), and unclassified (UC) subtype. However, this classification with prognostic significance was not applied into clinical practice since there were more than 1000 genes to detect and interpreting was difficult. To classify cancer samples validly, eight significant genes (MYBL1, LMO2, BCL6, MME, IRF4, NFKBIZ, PDE4B, and SLA) were selected in 414 patients treated with CHOP/R-CHOP chemotherapy from Gene Expression Omnibus (GEO) data sets. Cutoffs for each gene were obtained using receiver-operating characteristic curves (ROC) new model based on the support vector machine (SVM) estimated the probability of membership into one of two subgroups: GCB and Non-GCB (ABC and UC). Furtherly, multivariate analysis validated the model in another two cohorts including 855 cases in all. As a result, patients in the training and validated cohorts were stratified into two subgroups with 94.0%, 91.0%, and 94.4% concordance with GEP, respectively. Patients with Non-GCB subtype had significantly poorer outcomes than that with GCB subtype, which agreed with the prognostic power of GEP classification. Moreover, the similar prognosis received in the low (0-2) and high (3-5) IPI scores group demonstrated that the new model was independent of IPI as well as GEP method. In conclusion, our new model could stratify DLBCL patients with CHOP/R-CHOP regimen matching GEP subtypes effectively. PMID- 26869287 TI - Risk Factors for Symptoms of Depression and Anxiety One Year Poststroke: A Longitudinal Study. AB - OBJECTIVE: To estimate the relative contribution of psychological factors next to sociodemographic and premorbid/stroke-related factors to the risk of developing symptoms of depression and anxiety after stroke. DESIGN: Multicenter, longitudinal cohort study. SETTING: Patients after stroke from 6 general hospitals. PARTICIPANTS: Patients (N=331) were included at stroke onset and followed up 2 and 12 months after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic and premorbid/stroke-related information was recorded during hospital admission, whereas psychological characteristics were determined with postal questionnaires 2 months poststroke. Symptoms of depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS) 2 and 12 months poststroke. Multivariable logistic analysis was performed to analyze the influence of sociodemographic, premorbid/stroke-related, and psychological characteristics on depressive symptoms (depression subscale of HADS >7) and symptoms of anxiety (anxiety subscale of HADS >7) 1 year after stroke. RESULTS: Early depression, stroke severity, posterior cerebral artery stroke, and neuroticism independently explained the variance of depressive symptoms 1 year poststroke (discriminative power, 83%; adjusted R(2) value, 36%). Neuroticism and early anxiety independently explained the variance of symptoms of anxiety 1 year poststroke (discriminative power, 88%; adjusted R(2) value, 44%). Based on these predictive models, nomograms were constructed to visually reflect the individual contribution of each risk factor to the development of long-term mood disorders after stroke. CONCLUSIONS: Psychological characteristics are important risk factors for poststroke symptoms of depression and anxiety. PMID- 26869284 TI - Stroke prevention in atrial fibrillation and 'real world' adherence to guidelines in the Balkan Region: The BALKAN-AF Survey. AB - Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 +/- 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% +/- 22.3%). Age >= 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region. PMID- 26869288 TI - Short-Term Improvement in Physical Activity and Body Composition After Supervised Exercise Training Program in Idiopathic Pulmonary Fibrosis. AB - OBJECTIVE: To examine the effect of participating in a 12-week supervised exercise training (ET) program on physical activity and body composition in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Randomized controlled trial assessing physical activity and body composition at baseline, after 12-week intervention, and at 11 months follow-up. SETTING: Outpatient hospital. PARTICIPANTS: Patients with IPF (N=34; mean age, 68+/-8y) recruited for this study; 32 patients completed the 12-week intervention (ET group: n=15; control group: n=17) and 28 patients (14 in each group) reassessed at 11-month follow-up from baseline. INTERVENTIONS: Participation in a 12-week supervised ET program or regular medical treatment. MAIN OUTCOME MEASURES: Changes in physical activity levels as measured by the International Physical Activity Questionnaire. RESULTS: After the 12-week intervention, physical activity levels were significantly increased in the ET group whereas the control group showed a trend toward deterioration (median difference between the groups, 2164MET-min/wk [interquartile range, 1576MET-min/wk]; MET = metabolic equivalent; P<.001). Body composition was also significantly improved in the ET group, whereas the control group showed an opposite trend. At 11-month follow-up, no significant differences were observed between the 2 groups in all variables. The ET group lost most of the achieved improvements in the outcomes and returned to near baseline levels, whereas the control group showed a trend toward worsened outcomes. CONCLUSIONS: Physical activity and body composition in patients with IPF were improved after a 12-week supervised ET program, although the benefits were not sustained at 11 month follow-up. These results may support the efficacy of participation in supervised ET to improve physical activity and body composition in patients with IPF; however, maintenance strategies are warranted to preserve the improved outcomes. PMID- 26869289 TI - Oncogenic Gene Fusion FGFR3-TACC3 Is Regulated by Tyrosine Phosphorylation. AB - Fibroblast growth factor receptors (FGFR) are critical for cell proliferation and differentiation. Mutation and/or translocation of FGFRs lead to aberrant signaling that often results in developmental syndromes or cancer growth. As sequencing of human tumors becomes more frequent, so does the detection of FGFR translocations and fusion proteins. The research conducted in this article examines a frequently identified fusion protein between FGFR3 and transforming acidic coiled-coil containing protein 3 (TACC3), frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Using titanium dioxide based phosphopeptide enrichment (TiO2)-liquid chromatography (LC)-high mass accuracy tandem mass spectrometry (MS/MS), it was demonstrated that the fused coiled-coil TACC3 domain results in constitutive phosphorylation of key activating FGFR3 tyrosine residues. The presence of the TACC coiled-coil domain leads to increased and altered levels of FGFR3 activation, fusion protein phosphorylation, MAPK pathway activation, nuclear localization, cellular transformation, and IL3-independent proliferation. Introduction of K508R FGFR3 kinase-dead mutation abrogates these effects, except for nuclear localization which is due solely to the TACC3 domain. IMPLICATIONS: These results demonstrate that FGFR3 kinase activity is essential for the oncogenic effects of the FGFR3 TACC3 fusion protein and could serve as a therapeutic target, but that phosphorylated tyrosine residues within the TACC3-derived portion are not critical for activity. Mol Cancer Res; 14(5); 458-69. (c)2016 AACR. PMID- 26869290 TI - SGK Kinase Activity in Multiple Myeloma Cells Protects against ER Stress Apoptosis via a SEK-Dependent Mechanism. AB - To assess the role of the serum and glucocorticoid-regulated kinase (SGK) kinase in multiple myeloma, we ectopically expressed wild type or a phosphomimetic version of SGK into multiple myeloma cell lines. These cells were specifically resistant to the ER stress inducers tunicamycin, thapsigargin, and bortezomib. In contrast, there was no alteration of sensitivity to dexamethasone, serum starvation, or mTORC inhibitors. Mining of genomic data from a public database indicated that low baseline SGK expression in multiple myeloma patients correlated with enhanced ability to undergo a complete response to subsequent bortezomib treatment and a longer time to progression and overall survival following treatment. SGK overexpressing multiple myeloma cells were also relatively resistant to bortezomib in a murine xenograft model. Parental/control multiple myeloma cells demonstrated a rapid upregulation of SGK expression and activity (phosphorylation of NDRG-1) during exposure to bortezomib and an SGK inhibitor significantly enhanced bortezomib-induced apoptosis in cell lines and primary multiple myeloma cells. In addition, a multiple myeloma cell line selected for bortezomib resistance demonstrated enhanced SGK expression and SGK activity. Mechanistically, SGK overexpression constrained an ER stress-induced JNK proapoptotic pathway and experiments with a SEK mutant supported the notion that SGK's protection against bortezomib was mediated via its phosphorylation of SEK (MAP2K4) which abated SEK/JNK signaling. These data support a role for SGK inhibitors in the clinical setting for myeloma patients receiving treatment with ER stress inducers like bortezomib. IMPLICATIONS: Enhanced SGK expression and activity in multiple myeloma cells contributes to resistance to ER stress, including bortezomib challenge. PMID- 26869292 TI - [Parkinsonian syndrome]. PMID- 26869291 TI - [Efficiency and good tolerance of rituximab for idiopathic thrombocytopenic purpura revealing a 22q11 deletion syndrome]. AB - INTRODUCTION: 22q11 deletion is a common genetic disorder which associates a polymalformative syndrome to dysimmune features. Autoimmunity and immune deficiency manifestations are often associated, resulting in a therapeutic challenge for this disease. CASE REPORT: We report a 28-year-old patient who presented with hemorrhagic manifestations leading to the diagnosis of severe thrombocytopenia (15,000/mm3), of both central and peripheral origin. Patient history, cardio-facial malformative syndrome, hypoparathyroidism and partial immune deficiency led to the molecular diagnosis of 22q11 deletion syndrome. After failure of polyvalent immunoglobulin infusions, rituximab alone allowed the increase of platelets to their usual level of 100-120,000/mm3 within 4 weeks and a complete clinical remission of the hemorrhagic syndrome, without any infectious complication after a 4-year follow-up. CONCLUSION: Rituximab may be an alternative to corticosteroid for the treatment of auto-immune manifestations associated with minor forms of 22q11 deletion syndrome without significant worsening of the immune deficiency. PMID- 26869294 TI - [Cutaneous lesion]. PMID- 26869293 TI - [Therapeutic endovascular procedures in aortitis]. AB - Aortitis is an inflammation of the aortic wall with an infectious or non infectious origin, which often progresses to vascular complications. The open surgical approach is a high-risk procedure for these pathologies. Endovascular interventions have improved the prognosis of patients with aortitis complications. This manuscript describes the pathophysiology responsible for vascular complications and the role of endovascular approach for their treatment. PMID- 26869295 TI - [Three cases of Jaccoud's arthropathy during systemic sclerosis]. AB - INTRODUCTION: Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis. CASE REPORTS: We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained. CONCLUSION: We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish. PMID- 26869296 TI - Quantitative determination of nine urinary metabolites of organophosphate flame retardants using solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). AB - Over the last few years, the use of organophosphate flame retardants (OPFRs) has been on the rise; however, there are knowledge gaps in both the human health effects of OPFRs and levels of human exposure. Currently, human biomonitoring data on the levels of OPFR metabolites in the Canadian population are still non existent. Herein we describe a novel method to measure nine urinary OPFR metabolites using solid phase extraction and ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The method detection limits were between 0.08 and 0.25ng/mL for target metabolites. The newly developed and validated method was applied to the analysis of 24 urine samples collected in 2010-12 from pregnant Canadian women. The most frequently detected OPFR metabolite in urine of study participants (detection frequency: 97%) was diphenyl phosphate (DPHP), with concentrations ranging between <0.13 25.2ng/mL, followed (75%) by the sum of two metabolites (DoCP: Di-o-cresyl phosphate and DpCP: Di-p- cresyl phosphate) of tricresyl phosphate, with concentrations between <0.13-4.38ng/mL. With the exception of desbutyl-tris-(2 butoxy-ethyl) phosphate which was not detected in any of the samples, all other OPFR metabolites measured were found among study participants with variable detection frequency, suggesting pregnant Canadian women may be exposed to OPFRs. PMID- 26869297 TI - Molecular Risk Factors for Schizophrenia. AB - Schizophrenia (SZ) is a complex and strongly heritable mental disorder, which is also associated with developmental-environmental triggers. As opposed to most diagnosable diseases (yet similar to other mental disorders), SZ diagnosis is commonly based on psychiatric evaluations. Recently, large-scale genetic and epigenetic approaches have been applied to SZ research with the goal of potentially improving diagnosis. Increased computational analyses and applied statistical algorithms may shed some light on the complex genetic and epigenetic pathways contributing to SZ pathogenesis. This review discusses the latest advances in molecular risk factors and diagnostics for SZ. Approaches such as these may lead to a more accurate definition of SZ and assist in creating extended and reliable clinical diagnoses with the potential for personalized treatment. PMID- 26869298 TI - Improving quality in healthcare: What makes a satisfied patient? AB - OBJECTIVE: To update the metric properties of a perceived quality questionnaire for patients admitted to hospital medical departments, to determine the level of patient satisfaction achieved, and to identify the variables which predict satisfaction. METHODS: Self-administered questionnaire completed at home following patient discharge, using a questionnaire prepared by the authors on a sample of 7207 users of medical departments in 9 public hospitals during the years 2006-2009. A principal component analysis with varimax rotation was performed. Reliability was assessed using internal consistency coefficient. An analysis was made of the compliance with each indicator reported by respondents. A logistic regression analysis was performed to determine the perceived quality dimensions which predicted overall patient satisfaction. RESULTS: The results of the reliability analysis indicated good coefficients for interpersonal manner (0.94) and professional competence (0.85) dimensions, and moderate values for the other dimensions (comfort 0.55, information 0.38, and organisation 0.37). Factor analyses showed single factors in each of the perceived quality dimensions, with a percentage of explained variance greater than 35% for information, interpersonal manner, professional competence, and comfort, and less than 30% for organisation. The dimensions which predicted satisfaction were interpersonal manner of healthcare staff, professional competence, and information. CONCLUSIONS: The metric properties of the questionnaire used have been updated, yielding a valid and reliable questionnaire for assessing patient satisfaction in quality management programmes, both for internal purposes and for conducting external comparisons. A positive relationship was obtained between the level of patient satisfaction and level of professional competence, interpersonal manner of healthcare staff, and information received. PMID- 26869300 TI - Erratum: Importance of Oceanian small mountainous rivers (SMRs) in global land-to ocean output of lignin and modern biospheric carbon. PMID- 26869299 TI - SOHLH2 is essential for synaptonemal complex formation during spermatogenesis in early postnatal mouse testes. AB - Spermatogenesis- and oogenesis-specific helix-loop-helix transcription factor 2 (SOHLH2) is exclusively expressed in germ cells of the gonads. Previous studies show that SOHLH2 is critical for spermatogenesis in mouse. However, the regulatory mechanism of SOHLH2 during early spermatogenesis is poorly understood. In the present study, we analyzed the gene expression profile of the Sohlh2 deficient testis and examined the role of SOHLH2 during spermatogenesis. We found 513 genes increased in abundance, while 492 genes decreased in abundance in 14 day-old Sohlh2-deficient mouse testes compared to wildtype mice. Gene ontology analysis revealed that Sohlh2 disruption effects the relative abundance of various meiotic genes during early spermatogenesis, including Spo11, Dmc1, Msh4, Prdm9, Sycp1, Sycp2, Sycp3, Hormad1, and Hormad2. Western blot analysis and immunostaining showed that SYCP3, a component of synaptonemal complex, was significantly less abundant in Sohlh2-deficient spermatocytes. We observed a lack of synaptonemal complex formation during meiosis in Sohlh2-deficient spermatocytes. Furthermore, we found that SOHLH2 interacted with two E-boxes on the mouse Sycp1 promoter and Sycp1 promoter activity increased with ectopically expressed SOHLH2. Taken together, our data suggest that SOHLH2 is critical for the formation of synaptonemal complexes via its regulation of Sycp1 expression during mouse spermatogonial differentiation. PMID- 26869302 TI - Dameshek W. Some speculations on the myeloproliferative syndromes [editorial]. Blood. 1951;6(4):372-375. PMID- 26869301 TI - Simple assembly of polysubstituted pyrazoles and isoxazoles via ring closure-ring opening domino reaction of 3-acyl-4,5-dihydrofurans with hydrazines and hydroxylamine. AB - A convenient general approach to 2-(pyrazol-4-yl)- and 2-(isoxazol-4-yl)ethanols based on the Bronsted acid-initiated reaction of 3-acyl-4,5-dihydrofurans with hydrazines or hydroxylamine was developed. Further transformation of the alcohol moiety in 2-(pyrazolyl)ethanols affording 2-(pyrazolyl)ethylamine as potent bioactive compounds as well as pyrazole-substituted derivatives of antitumor alkaloid crispine A was elaborated. PMID- 26869303 TI - Platelet antibody identification: toward a solution. PMID- 26869304 TI - BCR-ABL1 mutation ? ponatinib resistance. PMID- 26869305 TI - B cells help CD8+ T-cell responses. PMID- 26869306 TI - FOXO discriminates tonic from chronic in DLBCL. PMID- 26869307 TI - Origin of stem cells in the BM niche: new clues from mastocytosis. PMID- 26869308 TI - Gas6 fueling tumor-mediated thrombosis. PMID- 26869309 TI - Adult patients with parapneumonic empyema who may not require pleural drainage. PMID- 26869310 TI - (18)F-FDG-PET/CT in a case of prosthetic valve endocarditis. PMID- 26869311 TI - Systemic Inflammatory Response Syndrome after Percutaneous Nephrolithotomy: A Randomized Single-Blind Clinical Trial Evaluating the Impact of Irrigation Pressure. AB - PURPOSE: We evaluated the impact of intraoperative irrigation pressures on the risk of systemic inflammatory response after percutaneous nephrolithotomy. MATERIALS AND METHODS: Between January 2014 and March 2015, 90 patients with renal stones planned for percutaneous nephrolithotomy were randomized between low (80 mm Hg) and high (200 mm Hg) irrigation pressure. Patient demographics, perioperative outcomes and systemic inflammatory response incidence rates were compared using the chi-square and Wilcoxon signed rank tests. RESULTS: Mean patient age, gender, body mass index and other perioperative outcomes were similar in both arms. High pressure irrigation was associated with a higher risk of systemic inflammatory response syndrome (46%) compared to low pressure irrigation (11%, p=0.0002). On multivariate analysis only high irrigation pressure, paraplegia or neurogenic bladder and nonquinolone perioperative medication were predictive of postoperative systemic inflammatory response syndrome. CONCLUSIONS: High pressure fluid irrigation fluid increases the risk of postoperative systemic inflammatory response syndrome after percutaneous nephrolithotomy. PMID- 26869312 TI - Approximal and occlusal carious lesions: Restorative treatment decisions by California dentists. AB - BACKGROUND: Investigators use questionnaire surveys to evaluate treatment philosophies in dental practices. The aim of this study was to evaluate the management strategies California dentists use for approximal and occlusal carious lesions. METHODS: In May 2013, the authors e-mailed a questionnaire that addressed approximal and occlusal carious lesion management (detection and restorative threshold, preferred preparation type, and restorative materials) to 16,960 dentists in California. The authors performed a chi(2) statistical analysis to investigate the relationship between management strategies and respondent demographic characteristics. RESULTS: The authors received responses from 1,922 (11.3%) dentists; 42.6% of the respondents would restore approximal lesions at the dentinoenamel junction, and 33.4% would wait until the lesion reached the outer one-third of dentin. The preferred preparation type was the traditional Class II preparation. Dentists who graduated more recently (20 years or less) were more likely to delay approximal restorations (P < .0001); 49.9% of the more recent graduates would wait to restore an occlusal lesion until the outer one-third of dentin was involved, and 42.6% would restore a lesion confined to enamel. CONCLUSIONS: There is wide variety among California dentists regarding their restorative treatment decisions, with most dentists restoring a tooth earlier than the literature would advise. More recent dental graduates were more likely to place their restorative threshold at deeper lesions for approximal carious lesions. PRACTICAL IMPLICATIONS: Clinical evidence shows that noncavitated carious lesions can be remineralized; therefore, early restorative treatment may no longer be necessary or appropriate. Noninvasive and minimally invasive measures should be taken into consideration. PMID- 26869314 TI - Improving the thermostability and enhancing the Ca(2+) binding of the maltohexaose-forming alpha-amylase from Bacillus stearothermophilus. AB - The thermostability of the maltohexaose-forming alpha-amylase from Bacillus stearothermophilus (AmyMH) without added Ca(2+) was improved through structure based rational design in this study. Through comparison of a homologous model structure of AmyMH with the crystal structure of the thermostable alpha-amylase from Bacillus licheniformis, Ser242, which located at the beginning of fourth alpha-helix of the central (beta/alpha)8 barrel was selected for mutation to improve thermostability. In addition, an amide-containing side chain (Asn193) and a loop in domain B (DeltaIG mutation), which have been proven to be important for thermostability in corresponding position of other alpha-amylases, were also investigated. Five mutants carrying the mutations DeltaIG, N193F, S242A, DeltaIG/N193F, and DeltaIG/N193F/S242A were generated and their proteins characterized. The most thermostable mutant protein, DeltaIG/N193F/S242A, exhibited a 26-fold improvement in half-life at 95 degrees C compared to the wild type enzyme without added Ca(2+). Mutant DeltaIG/N193F/S242A also exhibited substantially better activity and stability in the presence of the chelator EDTA, demonstrating enhanced Ca(2+) binding. These results suggest that mutant DeltaIG/N193F/S242A has potential for use in the industrial liquefaction of starch. PMID- 26869313 TI - Network burst dynamics under heterogeneous cholinergic modulation of neural firing properties and heterogeneous synaptic connectivity. AB - The characteristics of neural network activity depend on intrinsic neural properties and synaptic connectivity in the network. In brain networks, both of these properties are critically affected by the type and levels of neuromodulators present. The expression of many of the most powerful neuromodulators, including acetylcholine (ACh), varies tonically and phasically with behavioural state, leading to dynamic, heterogeneous changes in intrinsic neural properties and synaptic connectivity properties. Namely, ACh significantly alters neural firing properties as measured by the phase response curve in a manner that has been shown to alter the propensity for network synchronization. The aim of this simulation study was to build an understanding of how heterogeneity in cholinergic modulation of neural firing properties and heterogeneity in synaptic connectivity affect the initiation and maintenance of synchronous network bursting in excitatory networks. We show that cells that display different levels of ACh modulation have differential roles in generating network activity: weakly modulated cells are necessary for burst initiation and provide synchronizing drive to the rest of the network, whereas strongly modulated cells provide the overall activity level necessary to sustain burst firing. By applying several quantitative measures of network activity, we further show that the existence of network bursting and its characteristics, such as burst duration and intraburst synchrony, are dependent on the fraction of cell types providing the synaptic connections in the network. These results suggest mechanisms underlying ACh modulation of brain oscillations and the modulation of seizure activity during sleep states. PMID- 26869316 TI - Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients. AB - Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients. PMID- 26869315 TI - Structure, expression and functions of MTA genes. AB - Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells. PMID- 26869318 TI - Molecular characterization of a human matrix attachment region that improves transgene expression in CHO cells. AB - Chinese hamster ovary (CHO) cells offer many advantages for recombinant gene expression, including proper folding and post-translational modification of the recombinant protein. However, due to positional effects resulting from the neighboring chromatin, transgenes are often expressed at low levels in these cells. While previous studies demonstrated that matrix attachment regions (MARs) can be utilized to increase transgene expression by buffering transgene silencing, the mechanism by which this occurs is poorly understood. We therefore performed a deletion analysis of the human beta-globin MAR sequence to characterize the regions that are necessary to enhance transgene expression in CHO cells. Our results indicate that of the six beta-globin MAR fragments tested (MAR-1-6; nucleotides 1-540, 420-1020, 900-1500, 1380-1980, 1860-2460, and 2340 2999, respectively), MAR-2, followed by MAR-3, was the most effective region for promoting stable and elevated transgene expression. Meanwhile, bioinformatic analyses demonstrated that these fragments encode a MAR-like motif and several transcription factor binding sites, including special AT-rich binding protein 1 (SATB1), CCAAT-enhancer-binding proteins (C/EBP), CCCTC-binding factor (CTCF), and Glutathione (GSH) binding motifs, indicating that these elements may contribute to the MAR-mediated enhancement of transgene expression. In addition, we found that truncated MAR derivatives yield more stable transgene expression levels than transgenes lacking the MAR. We concluded that the MAR-mediated transcriptional activation of transgenes requires a specific AT-rich sequence, as well as specific transcription factor-binding motifs. PMID- 26869317 TI - Expression analysis and characterization of an autosome-localized tesk1 gene in half-smooth tongue sole (Cynoglossus semilaevis). AB - Testis-specific protein kinase 1 (tesk1) represents a conserved gene family functioning in many cellular processes. In this study, we cloned and characterized an autosome-localized tesk1 gene (Altesk1) from Cynoglossus semilaevis. The open reading frame consists of 2088 nucleotides and encodes a 665 amino acid polypeptide. Phylogenetic analyses show that vertebrate Tesk1s are divided into two clusters based on protein length and AlTesk1 belongs to "long type" group. Semi-quantitative PCR reveals that Altesk1 is predominantly expressed in ovary, despite of relatively low detection in some other tissues. Among different development stages, Altesk1 transcripts are only observed in ovary samples of 210-day and 1-year fish. In situ hybridization analyses have further confirmed its major localization in oocyte cells. Comparison of methylation patterns in different sexual genotypes reveals the low methylation level of Altesk1 promoter in female, which is consistent with Altesk1 high expression level in female. Taken together, this is the first time that tesk1 gene has been found to show female-biased expression and in view of this, we postulate that AlTesk1 might be involved in some cellular processes specific in ovary, e.g. oogenesis. PMID- 26869319 TI - Phage M13 for the treatment of Alzheimer and Parkinson disease. AB - The studies of microbes have been instrumental in combatting infectious diseases, but they have also led to great insights into basic biological mechanism like DNA replication, transcription, and translation of mRNA. In particular, the studies of bacterial viruses, also called bacteriophage, have been quite useful to study specific cellular processes because of the ease to isolate their DNA, mRNA, and proteins. Here, I review the recent discovery of how properties of the filamentous phage M13 emerge as a novel approach to combat neurodegenerative diseases. PMID- 26869323 TI - Framework for Evaluating the Impact of Advanced Practice Nursing Roles. AB - PURPOSE: To address the gap in evidence-based information required to support the development of advanced practice nursing (APN) roles in Switzerland, stakeholders identified the need for guidance to generate strategic evaluation data. This article describes an evaluation framework developed to inform decisions about the effective utilization of APN roles across the country. APPROACH: A participatory approach was used by an international group of stakeholders. Published literature and an evidenced-based framework for introducing APN roles were analyzed and applied to define the purpose, target audiences, and essential elements of the evaluation framework. Through subsequent meetings and review by an expert panel, the framework was developed and refined. FINDINGS: A framework to evaluate different types of APN roles as they evolve to meet dynamic population health, practice setting, and health system needs was created. It includes a matrix of key concepts to guide evaluations across three stages of APN role development: introduction, implementation, and long-term sustainability. For each stage, evaluation objectives and questions examining APN role structures, processes, and outcomes from different perspectives (e.g., patients, providers, managers, policy makers) were identified. CONCLUSIONS: A practical, robust framework based on well established evaluation concepts and current understanding of APN roles can be used to conduct systematic evaluations. CLINICAL RELEVANCE: The evaluation framework is sufficiently generic to allow application in developed countries globally, both for evaluation as well as research purposes. PMID- 26869327 TI - Increased Reach of Genetic Cancer Risk Assessment as a Tool for Precision Management of Hereditary Breast Cancer. PMID- 26869328 TI - Kingella kingae-Associated Pediatric Osteoarticular Infections: An Overview of 566 Reported Cases. AB - This study aimed to summarize clinical experience with Kingella kingae-associated pediatric osteoarticular infections (OAIs). We reviewed 566 cases in the English literature from 2000 to June 2014. More than 80% of the patients were diagnosed between 4 months and 4 years of age, and the male to female ratio was 1.14:1. The most frequent preceding illness was upper respiratory tract infections (82%). The top 3 OAIs types were septic arthritis (73.1%), osteomyelitis (15.7%), and spondylodiscitis (5.4%), and the most affected sites of these types were knee (46%), calcaneus (20%), and L4/5 disc (70%). All cases where polymerase chain reaction (PCR) technique was used were PCR positive, no reported cases of positive cultures for K kingae with negative PCR. The duration of antibiotics use ranged from 2 to 4 weeks. Beta-lactam antibiotics were the most frequently used intravenously and orally. The clinical efficacy was favorable. PMID- 26869329 TI - Multidrug co-crystals: towards the development of effective therapeutic hybrids. AB - Co-crystals have garnered the interest of the pharmaceutical industry with the introduction of regulatory guidelines by the US Food and Drug Administration (FDA) as a result of expanded patent portfolios. The Phase II clinical success of tramadol and celecoxib co-crystal for the treatment of acute pain followed by a recent reflection paper published by the European Medicines Agency (EMA) have further boosted the development of drug-drug co-crystals. Here, we shed light on the developments of drug-drug co-crystals and highlight future perspectives for exploring new therapeutic hybrids deploying drug-drug, drug-nutraceuticals and drug-inorganic salt combinations with improved pharmaceutical and biopharmaceutical performance. PMID- 26869331 TI - [In Germany too many ICD implantations are performed: pro]. AB - Implantable cardioverter defibrillators (ICD) have undoubtedly developed into one of the most successful therapies in the field of cardiology over the last decades; however, a significant number of ICD operations are carried out in patients who do not benefit from ICD therapy despite significant left ventricular dysfunction. These patients can easily be identified. An ICD therapy does not prolong life in the setting of significant chronic kidney disease. In elderly patients the benefit of prophylactic ICD therapy is very small. Simple risk scores can identify other patients who do not benefit from this treatment. The number of ICD operations can also be significantly reduced by the use of devices with an extended longevity. PMID- 26869330 TI - [Hemodynamics and physical capacity in patients with left ventricular assist devices : An overview]. AB - In the course of time implantation of left ventricular assist devices (LVAD) has become an alternative to heart transplantation due to the enormous technical developments and miniaturization of these systems. Following implantation most patients show a significant improvement in their clinical condition and exercise capacity as measured by the New York Heart Association (NYHA) classification; nevertheless, exercise tolerance remains clearly limited even after LVAD implantation. The complex physiological and hemodynamic changes in LVAD patients both at rest and during exercise are ultimately not completely understood. The aim of this article is to describe the current state of scientific knowledge with respect to the physical capacity of patients with terminal heart failure after LVAD implantation at rest and during exercise. The influence of increasing the pump speed and continuous physical exercise training on the physical capacity in the long-term course is reviewed. The significance of new diagnostic tools, such as the non-invasive inert gas rebreathing method for measurement of cardiac output and arteriovenous oxygen difference (AVDO2) in assessment of the performance of LVAD patients is discussed. PMID- 26869332 TI - Gestational diabetic transcriptomic profiling of microdissected human trophoblast. AB - Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is influenced by the placenta, and its prevalence directly increases with obesity. Therefore, to define the aetiology of GDM requires that the confounding influence of obesity and the heterogeneous nature of the placenta impairing accurate quantitative studies be accounted for. Using laser capture microdissection (LCM), we optimized RNA extraction from human placental trophoblast, the metabolic cellular interface between mother and foetus. This allowed specific transcriptomic profiling of trophoblast isolated from GDM, and obese and normal human placentae. Genome-wide gene expression analysis was performed on the RNA extracted from the trophoblast of GDM and obese and normal placentae. Forty-five differentially expressed genes (DEGs) specifically discriminated GDM from matched obese subjects. Two genes previously linked with GDM, pregnancy specific beta-1 glycoprotein 6 (PSG6) and placental system A sodium-dependent transporter system (SLC38A1), were significantly increased in GDM. A number of these DEGs (8 ubiquitin-conjugating enzymes (UBE) splice variants (UBE2D3 variants 1, 3, 4, 5, 6, 7, and 9) and UBE2V1 variant 4)) were involved in RNA processing and splicing, and a significant number of the DEGs, including the UBE variants, were associated with increased maternal fasting plasma glucose.It is concluded that DEGs discriminating GDM from obese subjects were pinpointed. Our data indicate a biological link between genes involved in RNA processing and splicing, ubiquitination, and fasting plasma glucose in GDM taking into account obesity as the confounder. PMID- 26869333 TI - Sfrp5 mediates glucose-induced proliferation in rat pancreatic beta-cells. AB - The cellular and molecular mechanisms of glucose-stimulated beta-cell proliferation are poorly understood. Recently, secreted frizzled-related protein 5 (encoded by Sfrp5; a Wnt signaling inhibitor) has been demonstrated to be involved in beta-cell proliferation in obesity. A previous study demonstrated that glucose enhanced Wnt signaling to promote cell proliferation. We hypothesized that inhibition of SFRP5 contributes to glucose-stimulated beta-cell proliferation. In this study, we found that the Sfrp5 level was significantly reduced in high glucose-treated INS-1 cells, primary rat beta-cells, and islets isolated from glucose-infused rats. Overexpression of SFRP5 diminished glucose stimulated proliferation in both INS-1 cells and primary beta-cells, with a concomitant inhibition of the Wnt signaling pathway and decreased cyclin D2 expression. In addition, we showed that glucose-induced Sfrp5 suppression was modulated by the PI3K/AKT pathway. Therefore, we conclude that glucose inhibits Sfrp5 expression via the PI3K/AKT pathway and hence promotes rat pancreatic beta cell proliferation. PMID- 26869334 TI - Luteimonas tolerans sp. nov., isolated from hexachlorocyclohexane-contaminated soil. AB - A Gram-stain-negative, aerobic, rod-shaped, non-spore-forming, yellow pigmented bacterial strain (UM1T) was isolated from the hexachlorocyclohexane (HCH) contaminated dumpsite located at Ummari village in Lucknow, India. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain UM1T belongs to the genus Luteimonas with Luteimonas aestuarii B9T as the closest neighbour (97.2% 16S rRNA gene sequence similarity). The DNA G+C content of strain UM1T was 64.3 mol%. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). Main fatty acids were iso-C15:0, iso-C11:0, iso-C11:0 3-OH, iso-C17:0 and summed feature 9 (C16:0 10-methyl and/or iso-C17:1omega9c). Ubiquinone (Q-8) was the only respiratory quinone. Spermidine was detected as the major polyamine. The DNA-DNA relatedness value of strain UM1T with respect to its closest neighbour Luteimonas aestuarii B9T was well below 70 % (~49%). Thus, data obtained from phylogenetic analysis, DNA-DNA hybridization, and chemotaxonomical and biochemical analyses supports classification of strain UM1T as representative of a novel species of the genus Luteimonas, for which the name Luteimonas tolerans sp. nov. is proposed. The type strain is UM1T (=DSM 28473T=MCC 2572T=KCTC 42936T). PMID- 26869335 TI - Structural Insights into the Tetrameric State of Aspartate-beta-semialdehyde Dehydrogenases from Fungal Species. AB - Aspartate-beta-semialdehyde dehydrogenase (ASADH) catalyzes the second reaction in the aspartate pathway, a pathway required for the biosynthesis of one fifth of the essential amino acids in plants and microorganisms. Microarray analysis of a fungal pathogen T. rubrum responsible for most human dermatophytoses identified the upregulation of ASADH (trASADH) expression when the fungus is exposed to human skin, underscoring its potential as a drug target. Here we report the crystal structure of trASADH, revealing a tetrameric ASADH with a GAPDH-like fold. The tetramerization of trASADH was confirmed by sedimentation and SAXS experiments. Native PAGE demonstrated that this ASADH tetramerization is apparently universal in fungal species, unlike the functional dimer that is observed in all bacterial ASADHs. The helical subdomain in dimeric bacteria ASADH is replaced by the cover loop in archaeal/fungal ASADHs, presenting the determinant for this altered oligomerization. Mutations that disrupt the tetramerization of trASADH also abolish the catalytic activity, suggesting that the tetrameric state is required to produce the active fungal enzyme form. Our findings provide a basis to categorize ASADHs into dimeric and tetrameric enzymes, adopting a different orientation for NADP binding and offer a structural framework for designing drugs that can specifically target the fungal pathogens. PMID- 26869336 TI - The signaling pathways by which the Fas/FasL system accelerates oocyte aging. AB - In spite of great efforts, the mechanisms for postovulatory oocyte aging are not fully understood. Although our previous work showed that the FasL/Fas signaling facilitated oocyte aging, the intra-oocyte signaling pathways are unknown. Furthermore, the mechanisms by which oxidative stress facilitates oocyte aging and the causal relationship between Ca2+ rises and caspase-3 activation and between the cell cycle and apoptosis during oocyte aging need detailed investigations. Our aim was to address these issues by studying the intra-oocyte signaling pathways for Fas/FasL to accelerate oocyte aging. The results indicated that sFasL released by cumulus cells activated Fas on the oocyte by increasing reactive oxygen species via activating NADPH oxidase. The activated Fas triggered Ca2+ release from the endoplasmic reticulum by activating phospholipase C-gamma pathway and cytochrome c pathway. The cytoplasmic Ca2+ rises activated calcium/calmodulin-dependent protein kinase II (CaMKII) and caspase-3. While activated CaMKII increased oocyte susceptibility to activation by inactivating maturation-promoting factor (MPF) through cyclin B degradation, the activated caspase-3 facilitated further Ca2+releasing that activates more caspase-3 leading to oocyte fragmentation. Furthermore, caspase-3 activation and fragmentation were prevented in oocytes with a high MPF activity, suggesting that an oocyte must be in interphase to undergo apoptosis. PMID- 26869337 TI - Fibroblast Growth Factor-10 (FGF-10) Mobilizes Lung-resident Mesenchymal Stem Cells and Protects Against Acute Lung Injury. AB - FGF-10 can prevent or reduce lung specific inflammation due to traumatic or infectious lung injury. However, the exact mechanisms are poorly characterized. Additionally, the effect of FGF-10 on lung-resident mesenchymal stem cells (LR MSCs) has not been studied. To better characterize the effect of FGF-10 on LR MSCs, FGF-10 was intratracheally delivered into the lungs of rats. Three days after instillation, bronchoalveolar lavage was performed and plastic-adherent cells were cultured, characterized and then delivered therapeutically to rats after LPS intratracheal instillation. Immunophenotyping analysis of FGF-10 mobilized and cultured cells revealed expression of the MSC markers CD29, CD73, CD90, and CD105, and the absence of the hematopoietic lineage markers CD34 and CD45. Multipotency of these cells was demonstrated by their capacity to differentiate into osteocytes, adipocytes, and chondrocytes. Delivery of LR-MSCs into the lungs after LPS injury reduced the inflammatory response as evidenced by decreased wet-to-dry ratio, reduced neutrophil and leukocyte recruitment and decreased inflammatory cytokines compared to control rats. Lastly, direct delivery of FGF-10 in the lungs of rats led to an increase of LR-MSCs in the treated lungs, suggesting that the protective effect of FGF-10 might be mediated, in part, by the mobilization of LR-MSCs in lungs. PMID- 26869338 TI - Quantification and identification of microorganisms found on shell and kernel of fresh edible chestnuts in Michigan. AB - BACKGROUND: Chestnut is a relatively new cultivated crop for Michigan, and postharvest loss due to decay has been problematic as production has increased each year. In 2007, more than 25% of chestnuts were lost to postharvest decay, equivalent to approximately 5300 kg of fresh product. To determine the organisms responsible for decay, a microbiological survey was performed in 2006 and 2007 to identify microorganisms involved in postharvest shell (external surface) mold and internal kernel (edible portion) decay of chestnuts. RESULTS: Filamentous fungi including Penicillium expansum, Penicillium griseofulvum, Penicillium chrysogenum, Coniophora puteana, Acrospeira mirabilis, Botryosphaeria ribis, Sclerotinia sclerotiorum, Botryotinia fuckeliana (anamorph Botrytis cinerea) and Gibberella sp. (anamorph Fusarium sp.) were the predominant microorganisms that negatively impacted fresh chestnuts. Populations of microorganisms varied between farms, harvesting methods and chestnut parts. CONCLUSION: Chestnuts harvested from the orchard floor were significantly (P < 0.05) more contaminated than chestnuts harvested directly from the tree, by more than 2 log colony-forming units (CFU) g(-1) . In addition, a significant difference (P < 0.05) in the microbial population was seen between chestnuts submitted by different growers, with average count ranges of fungi, mesophilic aerobic bacteria (MAB) and yeasts equal to 4.75, 4.59 and 4.75 log CFU g(-1) respectively. (c) 2016 Society of Chemical Industry. PMID- 26869340 TI - Spectroscopic investigations into the binding of hydrogen sulfide to synthetic picket-fence porphyrins. AB - The reversible binding of hydrogen sulfide (H2S) to hemeprotein sites has been attributed to several factors, likely working in concert, including the protected binding pocket environment, proximal hydrogen bond interactions, and iron ligation environment. To investigate the importance of a sterically-constrained, protected environment on sulfide reactivity with heme centers, we report here the reactivity of H2S and HS(-) with the picket-fence porphyrin system. Our results indicate that the picket-fence porphyrin does not bind H2S in the ferric or ferrous state. By contrast, reaction of the ferric scaffold with HS(-) results in reduction to the ferrous species, followed by ligation of one equivalent of HS( ), as evidenced by UV-vis, NMR spectroscopy and mass spectrometry studies. Measurement of the HS(-) binding affinities in the picket-fence or tetraphenyl porphyrin systems revealed identical binding. Taken together, these results suggest that the protected, sterically-constrained binding pocket alone is not the primary contributor for stabilization of ferric H2S/HS(-) species in model systems, but that other interactions, such as hydrogen bonding, must play a critical role in facilitation of reversible interactions in ferric hemes. PMID- 26869339 TI - Auricular acupuncture for spinal cord injury related neuropathic pain: a pilot controlled clinical trial. AB - OBJECTIVE: To obtain preliminary data on the effects of an auricular acupuncture protocol, Battlefield Acupuncture (BFA), on self-reported pain intensity in persons with chronic Spinal Cord Injury (SCI) and neuropathic pain. DESIGN: Pilot randomized delayed entry single center crossover clinical trial at an outpatient rehabilitation and integrative medicine hospital center. METHODS: Chronic (> one year post injury) ASIA impairment scale A through D individuals with SCI with injury level from C3 through T12 and below level neuropathic pain with at least five on the Numeric Rating Scale (NRS) were recruited. Twenty-four subjects were randomized to either an eight-week once weekly ten-needle BFA protocol (n = 13) or to a waiting list followed by the BFA protocol (n = 11). OUTCOME MEASURES: The primary outcome measure was change in the pain severity NRS. Secondary outcome was the Global Impression of Change. RESULTS: Demographically there were no significant differences between groups. Mean pain scores at baseline were higher in acupuncture than control subjects (7.75 +/- 1.54 vs. 6.25 +/- 1.04, P = 0.027). Although both groups reported significant reduction in pain during the trial period, the BFA group reported more pain reduction than the delayed entry group (average change in NRS at eight weeks -2.92 +/- 2.11 vs. -1.13 +/- 2.14, P = 0.065). There was a significant difference in groups when a group-by-time interaction in a mixed-effect repeated measures model (P = 0.014). CONCLUSION: This pilot study has provided proof of concept that BFA has clinically meaningful effect on the modulation of SCI neuropathic pain. PMID- 26869341 TI - A sensitive method for the determination of hordenine in human serum by ESI+ UPLC MS/MS for forensic toxicological applications. AB - We present the determination of the alkaloid hordenine and its forensic relevance as a qualitative and quantitative marker for beer consumption. A simple, rapid and sensitive ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method for the determination of hordenine in human serum samples was developed and validated. The application was tested with serum samples after enzymatic cleavage. After addition of the synthesized internal standard hordenine-D 4, a liquid-liquid extraction with dichloromethane and diethyl ether was performed. Chromatographic separation was conducted with a Waters Acquity(r) UPLC system with gradient elution on an Agilent Eclipse XDB-C18 column (4.6 mm * 150 mm, 5-MUm particle size). For quantification, a Waters Acquity(r) TQ detector (version SNC 627) with a positive electrospray ionization probe and multiple reaction monitoring mode was used. A flow rate of 0.4 ml/min was applied. The retention time for both the analyte and the internal standard was 3.67 min. Linearity was demonstrated from 0.2 to 16 ng/ml (R(2) > 0.999). The lower limit of quantification was 0.3 ng/ml in serum. Matrix effects and extraction recoveries for low and high concentrations were within acceptable limits of 75-125% and 50%, respectively. To the best of our knowledge there is no corresponding method for the determination of hordenine by UPLC-MS/MS in serum. By our drinking studies we demonstrate that beer consumption leads to detectable hordenine concentrations in serum and observed a linear elimination of total hordenine correlating to blood alcohol concentration, which shows that hordenine can be used as a reliable qualitative and quantitative marker for beer consumption. The validated method was successfully applied to serum from actual forensic cases. PMID- 26869342 TI - Metabolites profiling of 10 bufadienolides in human liver microsomes and their cytotoxicity variation in HepG2 cell. AB - Bufadienolides, a class of polyhydroxy steroids, exhibit significant antitumor activity. In this study, a total of 39 metabolites from 10 bufadienolides were detected and identified by ultrahigh-performance liquid chromatography (UHPLC) coupled with an LTQ Orbitrap mass spectrometer. The results showed that hydroxylation and dehydrogenation were the major metabolic pathways of bufadienolides in human liver microsomes (HLMs). CYP3A4 was found to be the major metabolic enzyme and CYP2D6 only mediated the dehydrogenation reaction. A systematic validated cytotoxicity evaluation method for bufadienolide metabolites at equal equivalents was established. Hellebrigenin (1), hellebrigenol (2), arenobufagin (3), bufotalin (5), and bufalin (6) were selected to determine their cytotoxicity against HepG2 cells before and after incubation in HLMs. All the test samples were enriched by a validated solid-phase extraction (SPE) method. Although the cytotoxicities of metabolites were weaker than those of the parent compounds to different degrees, their effects were still strong. PMID- 26869343 TI - Simultaneous electrochemical determination of dopamine and 5-hydroxyindoleacetic acid in urine using a screen-printed graphite electrode modified with gold nanoparticles. AB - The authors describe a disposable screen-printed graphite electrode (SPGE) modified with gold nanoparticles (AuNPs). The electrode, designated as AuNPs SPGE, was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. The AuNPs-SPGE combines the electrochemical features of graphite and the disposability of screen-printed electrodes. It displays excellent electrocatalytic activity towards dopamine (DA) and 5-hydroxyindoleacetic acid (5 HIAA). Two well-defined, sharp, and fully resolved voltammetric peaks (at 525 mV for DA and at 415 mV for 5-HIAA, both vs. Ag/AgCl) were found. Square wave voltammetry was used to simultaneously determine DA and 5-HIAA in mixtures and in urine. The linear working range extends from 0.1 to 120.0 MUM for both DA and 5 HIAA, and the limits of detection (based on 3* the baseline noise) are 14.0 and 5.7 nM, respectively. The fabrication method for the AuNPs-SPGE is highly reproducible. The performance of the AuNPs-SPGE was evaluated by analyzing spiked human urine, and the recoveries were found to be well over 94.0 % for both compounds. These results indicate that the AuNPs-SPGE represents a highly selective and sensitive sensor for simultaneous determination of DA and 5-HIAA in urine. Graphical Abstract Fabrication, characterization and electrochemical behavior of gold nanoparticles modified screen-printed graphite electrode towards dopamine and 5-hydroxyindoleacetic acid in human urine. PMID- 26869344 TI - Evaluation of a reconfigurable portable instrument for copper determination based on luminescent carbon dots. AB - A portable reconfigurable platform for copper (Cu(II)) determination based on luminescent carbon dot (Cdots) quenching is described. The electronic setup consists of a light-emitting diode (LED) as the carbon dot optical exciter and a photodiode as a light-to-current converter integrated in the same instrument. Moreover, the overall analog conditioning is simply performed with one integrated solution, a field-programmable analog array (FPAA), which makes it possible to reconfigure the filter and gain stages in real time. This feature provides adaptability to use the platform as an analytical probe for carbon dots coming from different batches with some variations in luminescence characteristics. The calibration functions obtained that fit a modified Stern-Volmer equation were obtained using luminescence signals from Cdots quenching by Cu(II). The analytical applicability of the reconfigurable portable instrument for Cu(II) using Cdots has been successfully demonstrated in tap water analysis. PMID- 26869345 TI - Comparative study of organic matter chemical characterization using negative and positive mode electrospray ionization ultrahigh-resolution mass spectrometry. AB - The chemical characterization of dissolved organic matter (DOM) is critical for understanding carbon sequestration processes in soils. This work evaluated the use of electrospray ionization in both negative ion mode (ESI-) and positive ion mode (ESI+) for the characterization of DOM extracted from nine terrestrial sources using Fourier transform ion cyclotron mass spectrometry (FT-ICR-MS). The compositing of the peaks from ESI- to ESI+ modes increased the total assigned formulas from 23 to 63 % as compared to the traditional use of ESI- alone for DOM characterization. In general, there was a preferential increase in the number of assignments for the aliphatic and carbohydrate-like DOM components in the ESI+ mode. The soil-extracted DOM specifically exhibited greater increases in the aliphatic and carbohydrate-like DOM components with the combined use of ESI- and ESI+ modes likely due to the greater presence of aromatic DOM molecules that suppressed the ionization of these entities in ESI- mode. On the basis of these findings, we show that improved characterization of DOM is possible through the combined use of ESI- and ESI+ modes for FT-ICR-MS analysis, especially for samples rich in condensed aromatic and aromatic molecules. PMID- 26869346 TI - Electrochemical simulation of metabolic reactions of the secondary fungal metabolites alternariol and alternariol methyl ether. AB - Mycotoxins are secondary plant metabolites that have been found to cause severe diseases in humans and livestock. Exposure can take place on a daily basis since mycotoxins can be found not only in food, animal food, and dietary supplements but also in materials used in buildings. For this work, the Alternaria toxins alternariol (AOH) and alternariol methyl ether (AME) are chosen as representatives for this relevant compound class and are investigated regarding their oxidative phase I metabolism using a combination of electrochemical (EC) oxidation and high-resolution electrospray ionization mass spectrometry (HR-ESI MS). This previously established method has been proven to be a valuable tool for the electrochemical simulation of certain phase I metabolic reactions. A comparison of the electrochemically generated products with those formed during microsomal incubation demonstrates the potential of the method for the successful prediction of the main phase I metabolic reactions of mycotoxins. It can thus find use as a supportive method in the elucidation of the metabolic pathways of various mycotoxins. PMID- 26869347 TI - The genetic background of Parkinson's disease: current progress and future prospects. AB - Almost two decades of genetic research in Parkinson's disease (PD) have remarkably increased our knowledge regarding the genetic basis of PD with numerous genes and genetic loci having been found to cause familial PD or affect the risk for PD. Approximately 5-10% of PD patients have monogenic forms of the disease, exhibiting a classical Mendelian type of inheritance, however, the majority PD cases are sporadic, probably caused by a combination of genetic and environmental risk factors. Nowadays, six genes, alpha synuclein, LRRK2, VPS35, Parkin, PINK1 and DJ-1, have definitely been associated with an autosomal dominant or recessive PD mode of inheritance. The advent of genome-wide association studies (GWAS) and the implementation of new technologies, like next generation sequencing (NGS) and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic PD. In this review, we will summarize the current progress and future prospects in the field of PD genetics. PMID- 26869348 TI - Living donor liver transplantation in maple syrup urine disease - Case series and world's youngest domino liver donor and recipient. AB - MSUD occurs due to deficiency of enzyme BCKAD required for metabolism of leucine, isoleucine, and valine leading to the accumulation of these and their ketoacids causing acute metabolic decompensation manifesting as encephalopathy or sudden death. The patient requires special protein-restricted diet to survive. As this enzyme is expressed in liver, liver transplantation has been successfully performed as a cure. We report two patients of MSUD who underwent LDLT while their livers were used as a domino graft for other biliary cirrhotic patients. A 22-month-old male child diagnosed as a case of classic MSUD underwent LDLT from an altruistic aunt as donor following which his serum leucine levels normalized on an unrestricted protein diet. His liver was used as a domino graft. A 38-month old female child with diagnosed MSUD underwent LDLT from a swap donor, and her liver was used as a domino graft. Her DQ improved post-transplant. LDLT from non heterozygous donors is a cure for classical MSUD. Their livers can be used as domino grafts for non-MSUD cases. PMID- 26869350 TI - Inhibition of Mitochondrial Fission and NOX2 Expression Prevent NLRP3 Inflammasome Activation in the Endothelium: The Role of Corosolic Acid Action in the Amelioration of Endothelial Dysfunction. AB - AIMS: Corosolic acid (CRA) is a natural triterpenoid with antioxidative activity. This study was designed to elucidate the mechanism through which CRA protected vessel endothelial homeostasis by combating oxidative stress. RESULTS: In endothelial cells, CRA induced dynamin-related protein 1 (Drp1) phosphorylation at Ser637 and thus inhibited mitochondrial fission in response to oxidative stress. It promoted AMP-activated protein kinase (AMPK) activity in an LKB1 dependent manner, and silencing AMPK abrogated its inhibitory effect on Drp1 activation and mitochondrial fission. CRA inhibited the translocation of p47(phox) and p67(phox) and the overexpression of gp91(phox) induced by palmitate (PA), demonstrating its action in suppression of NOX2 activation. Drp1 knockdown reduced PA-induced gp91(phox) expression, while Drp1 induction was also diminished by gp91(phox) knockdown, suggesting the reciprocal relationship between NOX2 and Drp1. Knockdown Drp1 or gp91(phox) attenuated PA-induced NLRP3 induction and enhanced inhibitory effects of CRA. Oral administration of CRA in high-fat diet mice reproduced similar regulation in the aorta endothelium, further confirming its protection on endothelial homeostasis in vivo. INNOVATION: This study demonstrated that the defect in mitochondrial morphology is associated with the oxidative stress and NLRP3 inflammasome activation in the endothelium. Drp1 and NOX2 regulated each other and worked together to induce NLRP3 inflammasome activation, suggesting that modulation of Drp1 phosphorylation (Ser637) might be a potential therapeutic target for combating oxidative stress in vessel diseases. CONCLUSION: CRA prevented mitochondrial fission by regulation of Drp1 phosphorylation (Ser637) in an AMPK-dependent manner, and this action contributed to blocking NOX2 oxidase signaling and suppressing NLRP3 inflammasome activation in the endothelium. Antioxid. Redox Signal. 24, 893-908. PMID- 26869349 TI - The mRNA-edited form of GABRA3 suppresses GABRA3-mediated Akt activation and breast cancer metastasis. AB - Metastasis is a critical event affecting breast cancer patient survival. To identify molecules contributing to the metastatic process, we analysed The Cancer Genome Atlas (TCGA) breast cancer data and identified 41 genes whose expression is inversely correlated with survival. Here we show that GABAA receptor alpha3 (Gabra3), normally exclusively expressed in adult brain, is also expressed in breast cancer, with high expression of Gabra3 being inversely correlated with breast cancer survival. We demonstrate that Gabra3 activates the AKT pathway to promote breast cancer cell migration, invasion and metastasis. Importantly, we find an A-to-I RNA-edited form of Gabra3 only in non-invasive breast cancers and show that edited Gabra3 suppresses breast cancer cell invasion and metastasis. A to-I-edited Gabra3 has reduced cell surface expression and suppresses the activation of AKT required for cell migration and invasion. Our study demonstrates a significant role for mRNA-edited Gabra3 in breast cancer metastasis. PMID- 26869351 TI - Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice. AB - Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable with control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL6 levels, expression of proinflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus nonobese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression. Cancer Prev Res; 9(5); 339-48. (c)2016 AACR. PMID- 26869352 TI - Site-specific and linkage analyses of fucosylated N-glycans on haptoglobin in sera of patients with various types of cancer: possible implication for the differential diagnosis of cancer. AB - Fucosylation is an important type of glycosylation involved in cancer, and fucosylated proteins could be employed as cancer biomarkers. Previously, we reported that fucosylated N-glycans on haptoglobin in the sera of patients with pancreatic cancer were increased by lectin-ELISA and mass spectrometry analyses. However, an increase in fucosylated haptoglobin has been reported in various types of cancer. To ascertain if characteristic fucosylation is observed in each cancer type, we undertook site-specific analyses of N-glycans on haptoglobin in the sera of patients with five types of operable gastroenterological cancer (esophageal, gastric, colon, gallbladder, pancreatic), a non-gastroenterological cancer (prostate cancer) and normal controls using ODS column LC-ESI MS. Haptoglobin has four potential glycosylation sites (Asn184, Asn207, Asn211, Asn241). In all cancer samples, monofucosylated N-glycans were significantly increased at all glycosylation sites. Moreover, difucosylated N-glycans were detected at Asn 184, Asn207 and Asn241 only in cancer samples. Remarkable differences in N-glycan structure among cancer types were not observed. We next analyzed N-glycan alditols released from haptoglobin using graphitized carbon column LC-ESI MS to identify the linkage of fucosylation. Lewis-type and core type fucosylated N-glycans were increased in gastroenterological cancer samples, but only core-type fucosylated N-glycan was relatively increased in prostate cancer samples. In metastatic prostate cancer, Lewis-type fucosylated N-glycan was also increased. These data suggest that the original tissue/cell producing fucosylated haptoglobin is different in each cancer type and linkage of fucosylation might be a clue of primary lesion, thereby enabling a differential diagnosis between gastroenterological cancers and non-gastroenterological cancers. PMID- 26869353 TI - Fatigue, patient reported outcomes, and objective measurement of physical activity in systemic lupus erythematosus. AB - OBJECTIVE: Fatigue is a common symptom in systemic lupus erythematosus (SLE), and engaging in physical activity may reduce fatigue. We aimed to characterize relationships between fatigue, other health status measures assessed with the Patient Reported Outcomes Measurement Information System (PROMIS) instruments, and accelerometer-based physical activity measurements in patients with SLE. The internal consistency of each PROMIS measure in our SLE sample was also evaluated. METHODS: This cross-sectional study analyzed 123 adults with SLE. The primary fatigue outcome was Fatigue Severity Scale score. Secondary outcomes were PROMIS standardized T-scores in seven health status domains. Accelerometers were worn for seven days, and mean daily minutes of light, moderate/vigorous, and bouted (10 minutes) moderate/vigorous physical activity were estimated. Cronbach's alpha was determined for each PROMIS measure to assess internal consistency. Relationships between Fatigue Severity Scale, PROMIS, and physical activity were summarized with Spearman partial correlation coefficients (r), adjusted for average daily accelerometer wear time. RESULTS: Mean Fatigue Severity Scale score (4.3, SD 1.6) was consistent with clinically relevant levels of fatigue. Greater daily and bouted moderate/vigorous physical activity minutes correlated with lower Mean Fatigue Severity Scale score (r = -0.20, p = 0.03 and r = -0.30, p = 0.0007, respectively). For PROMIS, bouted moderate/vigorous physical activity minutes correlated with less fatigue (r = -0.20, p = 0.03). PROMIS internal consistency was excellent, with Cronbach's alpha > 0.90 for each domain. Mean PROMIS T-scores for fatigue, pain interference, anxiety, sleep disturbance, sleep related impairment, and physical function were worse than reported for the general US population. More moderate/vigorous physical activity minutes were associated with less pain interference (r = -0.22, p = 0.01). Both light physical activity and moderate/vigorous physical activity minutes correlated with better physical function (r = 0.19, p = 0.04 and r = 0.25, p = 0.006, respectively). CONCLUSION: More time spent in moderate/vigorous physical activity was associated with less fatigue (Fatigue Severity Scale and PROMIS), less pain interference, and better physical function (PROMIS). PROMIS had excellent internal consistency in our SLE sample, and six of seven PROMIS measures indicated poorer average health status in SLE patients compared with the general US population. PMID- 26869354 TI - Glycolipid analyses of light-harvesting chlorosomes from envelope protein mutants of Chlorobaculum tepidum. AB - Chlorosomes are large and efficient light-harvesting organelles in green photosynthetic bacteria, and they characteristically contain large numbers of bacteriochlorophyll c, d, or e molecules. Self-aggregated bacteriochlorophyll pigments are surrounded by a monolayer envelope membrane comprised of glycolipids and Csm proteins. Here, we analyzed glycolipid compositions of chlorosomes from the green sulfur bacterium Chlorobaculum tepidum mutants lacking one, two, or three Csm proteins by HPLC equipped with an evaporative light-scattering detector. The ratio of monogalactosyldiacylglyceride (MGDG) to rhamnosylgalactosyldiacylglyceride (RGDG) was smaller in chlorosomes from mutants lacking two or three proteins in CsmC/D/H motif family than in chlorosomes from the wild-type, whereas chlorosomes lacking CsmIJ showed relatively less RGDG than MGDG. The results suggest that the CsmC, CsmD, CsmH, and other chlorosome proteins are involved in organizing MGDG and RGDG and thereby affect the size and shape of the chlorosome. PMID- 26869357 TI - Biosurfactant as a Promoter of Methane Hydrate Formation: Thermodynamic and Kinetic Studies. AB - Natural gas hydrates (NGHs) are solid non-stoichiometric compounds often regarded as a next generation energy source. Successful commercialization of NGH is curtailed by lack of efficient and safe technology for generation, dissociation, storage and transportation. The present work studied the influence of environment compatible biosurfactant on gas hydrate formation. Biosurfactant was produced by Pseudomonas aeruginosa strain A11 and was characterized as rhamnolipids. Purified rhamnolipids reduced the surface tension of water from 72 mN/m to 36 mN/m with Critical Micelle Concentration (CMC) of 70 mg/l. Use of 1000 ppm rhamnolipids solution in C type silica gel bed system increased methane hydrate formation rate by 42.97% and reduced the induction time of hydrate formation by 22.63% as compared to water saturated C type silica gel. Presence of rhamnolipids also shifted methane hydrate formation temperature to higher values relative to the system without biosurfactant. Results from thermodynamic and kinetic studies suggest that rhamnolipids can be applied as environment friendly methane hydrate promoter. PMID- 26869356 TI - PPARalpha modulates gene expression profiles of mitochondrial energy metabolism in oral tumorigenesis. AB - Metabolic reprogramming plays a crucial role in the development of cancer. The aim of this study was to explore the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha), on gene expression profiles of mitochondrial energy metabolism. Our results showed that PPARalpha expression was negatively correlated with tumor progression in an oral cancer mouse model. Activation of PPARalpha through fenofibrate suppressed migration of oral cancer cells. Differential protein profiling demonstrated that expressions of genes related to mitochondrial energy metabolism were either up-regulated (Atp5g3, Cyc1, Ndufa5, Ndufa10, and Sdhd) or down-regulated (Cox5b, Ndufa1, Ndufb7, and Uqcrh) through PPARalpha activation and response. Our results indicate that PPARalpha exhibits a great potential for anti-oral cancer therapies by modulating cancer cell mitochondrial energy metabolism. PMID- 26869358 TI - Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H(+) /K(+) ATPase Beta Subunit KO Mice. AB - Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by MUCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26869355 TI - Epigenetics, TET proteins, and hypoxia in epithelial-mesenchymal transition and tumorigenesis. AB - Hypoxia in tumors is primarily a pathophysiologic consequence of structurally and functionally disturbed microcirculation with inadequate supply of oxygen. Tumor hypoxia is strongly associated with tumor propagation, malignant progression, and resistance to therapy. Aberrant epigenetic regulation plays a crucial role in the process of hypoxia-driven malignant progression. Convert of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family enzymes plays important biological functions in embryonic stem cells, development, aging and disease. Recent reports showed that level of 5hmC and TET proteins was altered in various types of cancers. There is a strong correlation between loss of 5hmC and cancer development but research to date indicates that loss of TET activity is associated with the cancer phenotype but it is not clear whether TET proteins function as tumor suppressors or oncogenes. While loss of TET1 and TET2 expression is associated with solid cancers, implying a tumor suppressor role, TET1 exhibits a clear oncogenic role in the context of genomic rearrangements such as in MLL-fusion rearranged leukemia. Interestingly, hypoxia increases global 5hmC levels and upregulates TET1 expression in a HIF1alpha dependent manner. Recently, hypoxia-induced TET1 has been demonstrated to play another important role for regulating hypoxia-responsive gene expression and epithelial-mesenchymal transition (EMT) by serving as a transcription co activator. Furthermore, hypoxia-induced TET1 also regulates glucose metabolism and hypoxia-induced EMT through enhancing the expression of insulin induced gene 1 (INSIG1). The roles and mechanisms of action of 5hmC and TET proteins in ES cell biology and during embryonic development, as well as in cancer biology, will be the main focus in this review. PMID- 26869360 TI - Out-coupling of Longitudinal Photoacoustic Pulses by Mitigating the Phase Cancellation. AB - Waves of any kinds, including sound waves and light waves, can interfere constructively or destructively when they are overlapped, allowing for myriad applications. However, unlike continuous waves of a single frequency, interference of photoacoustic pulses is often overlooked because of their broadband characteristics and short pulse durations. Here, we study cancellation of two symmetric photoacoustic pulses radiated in the opposite direction from the same photoacoustic sources near a free surface. The cancellation occurs when one of the two pulses is reflected with polarity reversal from the free surface and catches up with the other. The cancellation effect, responsible for reduced signal amplitudes, is systematically examined by implementing a thin transparent matching medium of the same acoustic impedance. By changing the thickness of the transparent layer, the overlap of the two symmetric pulses is controlled. For optimized matching layers, the cancellation effect can be significantly reduced, while the resulting output waveform remains unchanged. Similar to the planar absorber, different dimensional absorbers including cylinders and spheres also exhibit the cancellation between the outward and inward waves. This work could provide further understanding of photoacoustic generation and a simple strategy for increasing photoacoustic signal amplitudes. PMID- 26869359 TI - People living with HIV travel farther to access healthcare: a population-based geographic analysis from rural Uganda. AB - INTRODUCTION: The availability of specialized HIV services is limited in rural areas of sub-Saharan Africa where the need is the greatest. Where HIV services are available, people living with HIV (PLHIV) must overcome large geographic, economic and social barriers to access healthcare. The objective of this study was to understand the unique barriers PLHIV face when accessing healthcare compared with those not living with HIV in a rural area of sub-Saharan Africa with limited availability of healthcare infrastructure. METHODS: We conducted a population-based cross-sectional study of 447 heads of household on Bugala Island, Uganda. Multiple linear regression models were used to compare travel time, cost and distance to access healthcare, and log binomial models were used to test for associations between HIV status and access to nearby health services. RESULTS: PLHIV travelled an additional 1.9 km (95% CI (0.6, 3.2 km), p=0.004) to access healthcare compared with those not living with HIV, and they were 56% less likely to access healthcare at the nearest health facility to their residence, so long as that facility lacked antiretroviral therapy (ART) services (aRR=0.44, 95% CI (0.24 to 0.83), p=0.011). We found no evidence that PLHIV travelled further for care if the nearest facility supplies ART services (aRR=0.95, 95% CI (0.86 to 1.05), p=0.328). Among those who reported uptake of care at one of two facilities on the island that provides ART (81% of PLHIV and 68% of HIV-negative individuals), PLHIV tended to seek care at a higher tiered facility that provides ART, even when this facility was not their closest facility (30% of PLHIV travelled further than the closest ART facility compared with 16% of HIV-negative individuals), and travelled an additional 2.2 km (p=0.001) to access that facility, relative to HIV-negative individuals (aRR=1.91, 95% CI (1.00 to 3.65), p=0.05). Among PLHIV, residential distance was associated with access to facilities providing ART (RR=0.78, 95% CI (0.61 to 0.99), p=0.044, comparing residential distances of 3-5 km to 0-2 km; RR=0.71, 95% CI (0.58 to 0.87), p=0.001, comparing residential distances of 6-10 km to 0-2 km). CONCLUSIONS: PLHIV travel longer distances for care, a phenomenon that may be driven by both the limited availability of specialized HIV services and preference for higher tiered facilities. PMID- 26869361 TI - Low-dose paclitaxel ameliorates renal fibrosis by suppressing transforming growth factor-beta1-induced plasminogen activator inhibitor-1 signaling. AB - AIM: To investigate the effect of microtubule stabilization with low-dose paclitaxel on renal fibrosis, focusing on the transforming growth factor-beta1 (TGF-beta1)-induced plasminogen activator inhibitor-1 (PAI-1) signaling cascade. METHODS: Forty-eight rats were randomly assigned to four groups: sham/vehicle, sham/paclitaxel, unilateral ureteral obstruction (UUO)/vehicle and UUO/paclitaxel. Rats were treated with a 0.3 mg/kg intraperitoneal dose of paclitaxel or vehicle twice per week for 14 days. Half of the rats in each group were sacrificed respectively on day 7 and 14 after operation. Inner medullar collecting duct (IMCD) cells stimulated with TGF-beta1 were incubated with 0, 1 and 2 nM paclitaxel for 24 and 72 hours. Histological changes were assessed using periodic acid-Schiff and Masson's trichrome. The TGF-beta1-induced PAI-1 signaling and status of extracellular matrix proteins were evaluated by western blot analysis. RESULTS: In the UUO kidneys, paclitaxel significantly attenuated tubular damage and interstitial collagen deposition, as well as alpha-smooth muscle actin (alpha-SMA), TGF-beta1 and PAI-1 protein expression. Paclitaxel also inhibited the UUO-induced activation of Smad2/3 and c-Jun N-terminal kinase (JNK). However, paclitaxel treatment did not inhibit extracellular signal regulated kinase 1/2 (ERK1/2) or p38 expression. In TGF-beta1-treated IMCD cells, treatment with 1 and 2 nM paclitaxel for 72 h reduced fibronectin, alpha-SMA and PAI-1 protein expression. Moreover, a 2 nM dose of paclitaxel for 24 h significantly inhibited the TGF-beta1-stimulated activation of Smad2/3, JNK and ERK1/2 in IMCD cells. CONCLUSION: Paclitaxel at low non-cytotoxic doses ameliorates renal fibrosis by inhibiting multiple steps in the TGF-beta1-induced PAI-1 signaling including Smads and mitogen-activated protein kinases. PMID- 26869362 TI - Dissociating emotional and cognitive empathy in pre-clinical and clinical Huntington's disease. AB - Huntington's disease (HD) is centrally characterized by motor, neurocognitive and psychiatric symptoms, but impaired emotional decoding abilities have also been reported. However, more complex affective abilities are still to be explored, and particularly empathy, which is essential for social relations and is impaired in various psychiatric conditions. This study evaluates empathic abilities and social skills in pre-clinical and clinical HD, and explores the distinction between two empathy sub-components (emotional-cognitive). Thirty-six HD patients (17 pre-clinical) and 36 matched controls filled in the Empathy Quotient Scale, while controlling for psychopathological comorbidities. At the clinical stage of HD, no global empathy impairment was observed but rather a specific deficit for the cognitive sub-component, while emotional empathy was preserved. A deficit was also observed for social skills. Pre-clinical HD was not associated with any empathy deficit. Emotional deficits in clinical HD are thus not limited to basic emotion decoding but extend towards complex interpersonal abilities. The dissociation between impaired cognitive and preserved emotional empathy in clinical HD reinforces the proposal that empathy subtypes are sustained by distinct processes. Finally, these results underline the extent of distinct affective and social impairments in HD and the need to grasp them in clinical contexts. PMID- 26869363 TI - Stereotactic radiosurgery for intramedullary spinal arteriovenous malformations. AB - Spinal cord arteriovenous malformations (AVM) are rare lesions associated with recurrent hemorrhage and progressive ischemia. Occasionally a favorable location, size or vascular anatomy may allow management with endovascular embolization and/or microsurgical resection. For most, however, there is no good treatment option. Between 1997 and 2014, we treated 37 patients (19 females, 18 males, median age 30years) at our institution diagnosed with intramedullary spinal cord AVM (19 cervical, 12 thoracic, and six conus medullaris) with CyberKnife (Accuray, Sunnyvale, CA, USA) stereotactic radiosurgery. A history of hemorrhage was present in 50% of patients. The mean AVM volume of 2.3cc was treated with a mean marginal dose of 20.5Gy in a median of two sessions. Clinical and MRI follow up were carried out annually, and spinal angiography was repeated at 3years. We report an overall obliteration rate of 19% without any post-treatment hemorrhagic events. In those AVM that did not undergo obliteration, significant volume reduction was noted at 3years. Although the treatment paradigm for spinal cord AVM continues to evolve, radiosurgical treatment is capable of safely obliterating or significantly shrinking most intramedullary spinal cord AVM. PMID- 26869364 TI - Consenting postpartum women for use of routinely collected biospecimens and/or future biospecimen collection. AB - The National Children's Study (NCS) Harris County, Texas Study Center participated in the NCS Provider Based Sampling (PBS) substudy of the NCS Vanguard Phase pilot. As part of the hospital-based birth cohort component of the PBS substudy, we conducted a secondary data analysis to evaluate the proportion of postpartum women who consented to future biospecimen collection alone and to both future collection and use of residual birth biospecimens. In phase 1, 32 postpartum women at one hospital were asked to consent only to maternal future biospecimen collection. In phase 2, 40 other postpartum women from the same hospital were asked for an additional consent to use residual clinical biospecimens from the birth event that otherwise would be discarded, including cord blood and maternal blood and urine. Among 103 eligible women, a total of 72 participated. They were 28.3 +/- 5.9 years old on average; 58 % were Hispanic; 63 % consented in English, and 37 % in Spanish; 39 % had some college education; 42 % were married; 60 % had an annual family income <$30,000; and 51 % were employed. In phase 1, 59 % consented to future biospecimen collection, and in phase 2, 95 % consented to both future collection and use of at least one residual birth biospecimen, with a difference between phases of 36 % [95 % CI 17 54 %]. Demographic characteristics did not differ among those who did and did not consent. Postpartum women were significantly more likely to grant consent for use of future and residual hospital-obtained biospecimens than future biospecimen collection alone. PMID- 26869365 TI - Hyperkeratosis in human lower limb lymphedema: the effect of stagnant tissue fluid/lymph. AB - BACKGROUND: Hyperkeratosis of skin in lower limb lymphedema is one of the sequelae of tissue fluid/lymph (TF/L) stasis, but its mechanisms remain unknown. It is noteworthy, nonetheless, that human TF/L contains high levels of growth factors and cytokines, and may serve as the physiological environment for keratinocyte (KC) proliferation. OBJECTIVE: The aim of the study was to investigate the effect of human TF/L on human KC proliferation, differentiation and on the expression of epidermal stem cell markers on them. METHODS: KC were isolated from lymphedema and normal skin, and cultured for 1-14 days in TF/L with neutralized Interleukin 1beta, Interleukin 6, tumour necrosis factor alpha (TNF alpha), keratinocyte growth factor (KGF) or tumour growth factor beta (TGF-beta). Alternatively, KC receptors for these factors were blocked. RESULTS: The number of KC cultured in TF/L was increased, as was the percentage of mitotic figures. There was a higher percentage of p63, CD29, Ki67, PCNA, CK6, CK17, CK16 and a lower of CK10, CK14, filaggrin and involucrin-positive KC. Neutralization of TF/L IL-1beta, IL-6, TNF-alpha and KGF as well as blockage of their receptors resulted in decreased percentage of mitotic KC. TGF-beta had a limited effect on KC proliferation. CONCLUSION: Hyperkeratosis in lymphedema may be the effect of a high concentration of cytokines in the stagnant TF/L tissue, but not because of presumed changes in the KC. PMID- 26869366 TI - Cyanobacterial origin of plant phytochromes. AB - Phytochromes are widely distributed photoreceptors with similar domain arrangements. The evolutionary origin of plant and green algal phytochromes is currently under debate. We used different algorithms to generate multiple phylogenetic trees for the N-terminal chromophore module and the C-terminal histidine kinase domains. The evolution of the chromophore module and the histidine kinase (like) regions follows different patterns, indicating several rearrangements between both parts of the protein. Out of 22 trees, 19 revealed a close relationship between cyanobacteria and Archaeplastida, the group encompassing plants and green algae. Opposed to other studies, a cyanobacterial origin of plant phytochromes is strongly supported by our results. PMID- 26869367 TI - CT myocardial perfusion and coronary CT angiography: Influence of coronary calcium on a stress-rest protocol. AB - BACKGROUND: High amounts of coronary artery calcium limit image quality and diagnostic accuracy of multidetector computed tomography (MDCT) angiography (CTA) regarding the assessment of obstructive coronary artery disease (CAD). CT myocardial perfusion imaging may represent an opportunity to overcome this limitation. OBJECTIVE: To explore the additive value of CT myocardial perfusion to CTA depending on the patient's calcium score and in comparison to the reference standard of invasive coronary angiography plus fractional flow reserve (FFR) measurement. METHODS: Symptomatic patients with intermediate pretest probability of CAD were prospectively recruited and underwent both cardiac MDCT (64-slice scanner, retrospectively-gated stress-rest protocol) and invasive coronary angiography including FFR assessment. We defined hemodynamically significant CAD by the presence of occlusive or subocclusive (99%) stenosis, >50% stenosis in left main or FFR<=0.80. Stress CT myocardial perfusion imaging was performed in all patients in addition to CTA. The additive value of CT myocardial perfusion to rule in or rule out the presence of hemodynamically relevant stenosis on a per-patient basis was assessed and analyzed relative to the patient's calcium score. RESULTS: 95 patients were included in the analysis (62 +/- 8.2 years, 68%males). Hemodynamically significant CAD was present in 42 patients. Sixty-four patients had a fully evaluable CTA examination. Per-patient, CTA alone had a sensitivity, specificity and AUC of 100%, 59% and 0.79 respectively (77% patients correctly classified). Adding CT myocardial perfusion to evaluate uninterpretable vessel territories in CTA in 66 patients with a calcium score>100 yielded a sensitivity of 88%, a specificity of 74% and an AUC of 0.81 (81% patients correctly classified), and in 52 patients with a calcium score>400 sensitivity was 91%, specificity 70%, and AUC 0.80 (82% patients correctly classified, p = 0.733 versus using perfusion imaging in all patients). CONCLUSIONS: From a pragmatic standpoint, limiting the use of CT perfusion to individuals with a calcium score above 400 might be a feasible strategy to optimize the diagnostic accuracy of CT imaging for diagnosis of obstructive CAD. PMID- 26869369 TI - Corrigendum: Point-of-service, quantitative analysis of ascorbic acid in aqueous humor for evaluating anterior globe integrity. PMID- 26869368 TI - Left Atrial Area and Right Ventricle Dimensions in Non-gated Axial Chest CT can Differentiate Pulmonary Hypertension Due to Left Heart Disease from Other Causes. AB - BACKGROUND: It is unknown whether axial non-gated CT can distinguish World Health Organization Group 2 pulmonary hypertension (pulmonary hypertension due to left heart disease) from non-Group 2 pulmonary hypertension. OBJECTIVE: The study was performed to identity imaging parameters in non-gated chest CT that differentiate Group 2 from non-Group 2 pulmonary hypertension. METHODS: Among 158 patients who underwent right heart catheterization for evaluation of pulmonary hypertension, 112 had sufficient data and chest CT for review. Invasive hemodynamic data and numerous variables obtained from axial CT images (maximum diameters of main, right, left pulmonary arteries, ascending aorta, main pulmonary artery to ascending aorta diameter ratio, right atrial diameter, left atrial area and right ventricular size) were collected. CT variables were validated against hemodynamic data to identify parameters that would allow to differentiate pulmonary hypertension due to left heart disease (Group 2) from non-Group 2 pulmonary hypertension. RESULTS: Based on right heart catheterization data, we identified 53 patients with Group 2 pulmonary hypertension, 50 patients with non-Group 2 pulmonary hypertension, and 9 subjects with no pulmonary hypertension. In patients with a dilated pulmonary artery (n = 84), the ROC curve for left atrial area (area under the ROC curve 0.76 +/- 0.06) independently distinguished patients with Group 2 pulmonary hypertension (n = 42) from patients with non Group 2 pulmonary hypertension (n = 42). A dilated left atrium (>20 mm(2)) in combination with a normal right ventriuclar size had a sensitivity of 77% and specificity of 94% for Group 2 pulmonary hypertension. CONCLUSIONS: In patients with a dilated pulmonary artery on chest CT, left atrial area and right ventricular dimensions may aid to diagnose pulmonary hypertension and to distinguish underlying cardiac disease from other causes. PMID- 26869370 TI - Parkinson's Disease with Fatigue: Clinical Characteristics and Potential Mechanisms Relevant to alpha-Synuclein Oligomer. AB - BACKGROUND AND PURPOSE: The aim of this study was to identify the clinical characteristics and potential mechanisms relevant to pathological proteins in Parkinson's disease (PD) patients who experience fatigue. METHODS: PD patients (n=102) were evaluated using a fatigue severity scale and scales for motor and nonmotor symptoms. The levels of three pathological proteins-alpha-synuclein oligomer, beta-amyloid (Abeta)1-42, and tau-were measured in 102 cerebrospinal fluid (CSF) samples from these PD patients. Linear regression analyses were performed between fatigue score and the CSF levels of the above-listed pathological proteins in PD patients. RESULTS: The frequency of fatigue in the PD patients was 62.75%. The fatigue group had worse motor symptoms and anxiety, depression, and autonomic dysfunction. The CSF level of alpha-synuclein oligomer was higher and that of Abeta1-42 was lower in the fatigue group than in the non fatigue group. In multiple linear regression analyses, fatigue severity was significantly and positively correlated with the alpha-synuclein oligomer level in the CSF of PD patients, after adjusting for confounders. CONCLUSIONS: PD patients experience a high frequency of fatigue. PD patients with fatigue have worse motor and part nonmotor symptoms. Fatigue in PD patients is associated with an increased alpha-synuclein oligomer level in the CSF. PMID- 26869371 TI - Cardiovagal Baroreflex Sensitivity in Parkinson's Disease and Multiple-System Atrophy. AB - BACKGROUND AND PURPOSE: Parkinson's disease (PD) and multiple-system atrophy of the parkinsonian type (MSA-P) are progressive neurodegenerative disorders that in addition to dysfunction of the motor system also present with features of dysautonomia, frequently manifesting as orthostatic hypotension (OH). The pathophysiology of OH has been proposed to differ between these two disorders. This study investigated the spontaneous and cardiovagal baroreflex sensitivity (BRS) in Parkinson's disease patients with orthostatic hypotension (PD(OH)) and multiple system atrophy of Parkinsonian type with orthostatic hypotension in an attempt to differentiate the two disorders. METHODS: Two methods were used for determining the BRS: a spontaneous method (spontaneous BRS) and the reflexive baroreflex gain (cardiovagal BRS) from phases II and IV of the Valsalva maneuver (VM) in PD(OH) and MSA-P(OH). RESULTS: The spontaneous BRS (5.04+/-0.66 ms/mm Hg vs. 4.78+/-0.64 ms/mm Hg, p=0.54) and the cardiovagal BRS from phase II of the VM (0.96+/-0.75 ms/mm Hg vs. 1.34+/-1.51 ms/mm Hg, p=0.76) did not differ between PD(OH) and MSA-P(OH), but the cardiovagal BRS from phase IV of the VM (0.03+/ 0.07 ms/mm Hg vs. 2.86+/-2.39 ms/mm Hg, p=0.004) was significantly lower in PD(OH). CONCLUSIONS: The cardiovagal BRS from phase IV of the VM has potential for differentiating PD(OH) and MSA-P(OH), indicating a difference in the pathophysiological mechanisms underlying the autonomic dysfunction in the two disorders. PMID- 26869372 TI - Babinski's Lost Legacy: A Remarkable Case of a Not-So-New Clinical Construct. PMID- 26869373 TI - Intrinsic Functional Hypoconnectivity in Core Neurocognitive Networks Suggests Central Nervous System Pathology in Patients with Myalgic Encephalomyelitis: A Pilot Study. AB - Exact low resolution electromagnetic tomography (eLORETA) was recorded from nineteen EEG channels in nine patients with myalgic encephalomyelitis (ME) and 9 healthy controls to assess current source density and functional connectivity, a physiological measure of similarity between pairs of distributed regions of interest, between groups. Current source density and functional connectivity were measured using eLORETA software. We found significantly decreased eLORETA source analysis oscillations in the occipital, parietal, posterior cingulate, and posterior temporal lobes in Alpha and Alpha-2. For connectivity analysis, we assessed functional connectivity within Menon triple network model of neuropathology. We found support for all three networks of the triple network model, namely the central executive network (CEN), salience network (SN), and the default mode network (DMN) indicating hypo-connectivity in the Delta, Alpha, and Alpha-2 frequency bands in patients with ME compared to controls. In addition to the current source density resting state dysfunction in the occipital, parietal, posterior temporal and posterior cingulate, the disrupted connectivity of the CEN, SN, and DMN appears to be involved in cognitive impairment for patients with ME. This research suggests that disruptions in these regions and networks could be a neurobiological feature of the disorder, representing underlying neural dysfunction. PMID- 26869374 TI - Does Brachial Plexus Blockade Result in Improved Pain Scores After Distal Radius Fracture Fixation? A Randomized Trial. AB - BACKGROUND: Distal radius fractures are very common injuries and surgical treatment for them can be painful. Achieving early pain control may help improve patient satisfaction and improve functional outcomes. Little is known about which anesthesia technique (general anesthesia versus brachial plexus blockade) is most beneficial for pain control after distal radius fixation which could significantly affect patients' postoperative course and experience. QUESTIONS/PURPOSES: We asked: (1) Did patients receiving general anesthesia or brachial plexus blockade have worse pain scores at 2, 12, and 24 hours after surgery? (2) Was there a difference in operative suite time between patients who had general anesthesia or brachial plexus blockade, and was there a difference in recovery room time? (3) Did patients receiving general anesthesia or brachial plexus blockade have higher narcotic use after surgery? (4) Do patients receiving general anesthesia or brachial plexus blockade have higher functional assessment scores after distal radius fracture repair at 6 weeks and 12 weeks after surgery? METHODS: A randomized controlled study was performed between February, 2013 and April, 2014 at a multicenter metropolitan tertiary-care referral center. Patients who presented with acute closed distal radius fractures (Orthopaedic Trauma Association 23A-C) were potentially eligible for inclusion. During the study period, 40 patients with closed, displaced, and unstable distal radius fractures were identified as meeting inclusion criteria and offered enrollment and randomization. Three patients (7.5%), all with concomitant injuries, declined to participate at the time of randomization as did one additional patient (2.5%) who chose not to participate, leaving a final sample of 36 participants. There were no dropouts after randomization, and analyses were performed according to an intention-to-treat model. Patients were randomly assigned to one of two groups, general anesthesia or brachial plexus blockade, and among the 36 patients included, 18 were randomized to each group. Medications administered in the postanesthesia care unit were recorded. Patients were discharged receiving oxycodone and acetaminophen 5/325 mg for pain control, and VAS forms were provided. Patients were called at predetermined intervals postoperatively (2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours) to gather pain scores, using the VAS, and to document the doses of analgesics consumed. In addition, patients had regular followups at 2 weeks, 6 weeks, and 12 weeks. Pain scores were again recorded using the VAS at these visits. RESULTS: Patients who received general anesthesia had worse pain scores at 2 hours postoperatively (general anesthesia 6.7 +/- 2.3 vs brachial plexus blockade 1.4 +/- 2.3; mean difference, 5.381; 95% CI, 3.850-6.913; p < 0.001); whereas reported pain was worse for patients who received a brachial plexus blockade at 12 hours (general anesthesia 3.8 +/- 1.9 vs brachial plexus blockade 6.3 +/- 2.4; mean difference, 2.535; 95% CI, -4.028 to -1.040; p = 0.002) and 24 hours (general anesthesia 3.8 +/- 2.2 vs brachial plexus blockade 5.3 +/- 2.5; mean difference, -1.492; 95% CI, -3.105 to 0.120; p = 0.031).There was no difference in operative suite time (general anesthesia 119 +/- 16 minutes vs brachial plexus blockade 125 +/- 23 minutes; p = 0.432), but time in the recovery room was greater for patients who received general anesthesia (284 +/- 137 minutes vs 197 +/- 90; p = 0.0398). Patients who received general anesthesia consumed more fentanyl (64 MUg +/- 93 MUg vs 6.9 MUg +/- 14 MUg; p < 0.001) and morphine (2.9 MUg +/- 3.6 MUg vs 0.0 MUg; p < 0.001) than patients who received brachial plexus blockade. Functional outcome scores did not differ at 6 weeks (data, with mean and SD for both groups, and p value) or 12 weeks postoperatively (data, with mean and SD for both groups, and p value). CONCLUSIONS: Brachial plexus blockade pain control during the immediate perioperative period was not significantly different from that of general anesthesia in patients undergoing operative fixation of distal radius fractures. However, patients who received a brachial plexus blockade experienced an increase in pain between 12 to 24 hours after surgery. Acknowledging "rebound pain" after the use of regional anesthesia coupled with patient counseling regarding early narcotic administration may allow patients to have more effective postoperative pain control. It is important to have a conversation with patients preoperatively about what to expect regarding rebound pain, postoperative pain control, and to advise them about being aggressive with taking pain medication before the waning of regional anesthesia to keep one step ahead in their pain control management. LEVEL OF EVIDENCE: Level 1, therapeutic study. PMID- 26869375 TI - "Super-quenching" state protects Symbiodinium from thermal stress - Implications for coral bleaching. AB - The global rise in sea surface temperatures causes regular exposure of corals to high temperature and high light stress, leading to worldwide disastrous coral bleaching events (loss of symbiotic dinoflagellates (Symbiodinium) from reef building corals). Our picosecond chlorophyll fluorescence experiments on cultured Symbiodinium clade C cells exposed to coral bleaching conditions uncovered the transformations of the alga's photosynthetic apparatus (PSA) that activate an extremely efficient non-photochemical "super-quenching" mechanism. The mechanism is associated with a transition from an initially heterogeneous photosystem II (PSII) pool to a homogeneous "spillover" pool, where nearly all excitation energy is transferred to photosystem I (PSI). There, the inherently higher stability of PSI and high quenching efficiency of P(700)(+) allow dumping of PSII excess excitation energy into heat, resulting in almost complete cessation of photosynthetic electron transport (PET). This potentially reversible "super quenching" mechanism protects the PSA against destruction at the cost of a loss of photosynthetic activity. We suggest that the inhibition of PET and the consequent inhibition of organic carbon production (e.g. sugars) in the symbiotic Symbiodinium provide a trigger for the symbiont expulsion, i.e. bleaching. PMID- 26869376 TI - Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. AB - BACKGROUND: Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa. METHODS: In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per MUL], and infection and low CD4 cell count [>50 to <=350 cells per MUL]) and received a 5 MUg dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24-35 weeks' gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801. FINDINGS: 270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV infected groups. Transfer ratios were similar across all three groups (0.49-0.72; transfer ratio is infant geometric mean antibody concentration in blood collected within 72 h of birth divided by maternal geometric mean antibody concentration in blood collected at delivery); however, at birth, maternally derived serotype specific antibody concentrations were lower for infants born to women infected with HIV (0.52-1.62 MUg/mL) than for those born to women not infected with HIV (2.67-3.91 MUg/mL). 151 (57%) of 265 women reported at least one solicited adverse reaction: 39 (45%) of 87 women with HIV and low CD4 cell counts, 52 (59%) of 88 women with HIV and high CD4 cell counts, and 60 (67%) of 90 women in the HIV-uninfected group. 49 (18%) of 269 women had at least one adverse event deemed possibly related to the vaccine (six [7%] in the HIV and low CD4 cell count group, 12 [13%] in the HIV and high CD4 cell count group, and 21 [23%] in the HIV uninfected group), as did three (1%) of 266 neonates (zero, two [1%], and one [1%]); none of these events was regarded as serious. INTERPRETATION: The vaccine was less immunogenic in women infected with HIV than it was in those not infected, irrespective of CD4 cell count, resulting in lower levels of serotype specific maternal antibody transferred to infants, which could reduce vaccine protection against invasive GBS disease. A validated assay and correlate of protection is needed to understand the potential protective value of this vaccine. FUNDING: Novartis Vaccines and Diagnostics division (now part of the GlaxoSmithKline group of companies), Wellcome Trust UK, Medical Research Council: Respiratory and Meningeal Pathogens Research Unit. PMID- 26869378 TI - En route towards prevention of neonatal group B streptococcal disease. PMID- 26869377 TI - Safety of artemisinins in first trimester of prospectively followed pregnancies: an observational study. AB - BACKGROUND: Artemisinins, the most effective antimalarials available, are not recommended for falciparum malaria during the first trimester of pregnancy because of safety concerns. Therefore, quinine is used despite its poor effectiveness. Assessing artemisinin safety requires weighing the risks of malaria and its treatment. We aimed to assess the effect of first-trimester malaria and artemisinin treatment on miscarriage and major congenital malformations. METHODS: In this observational study, we assessed data from antenatal clinics on the Thai-Myanmar border between Jan 1, 1994, and Dec 31, 2013. We included women who presented to antenatal clinics during their first trimester with a viable fetus. Women were screened for malaria, and data on malaria, antimalarial treatment, and birth outcomes were collected. The relationship between artemisinin treatments (artesunate, dihydroartemisinin, or artemether) and miscarriage or malformation was assessed using Cox regression with left-truncation and time-varying exposures. FINDINGS: Of 55 636 pregnancies registered between 1994 and 2013, 25 485 pregnancies were analysed for first trimester malaria and miscarriage, in which 2558 (10%) had first-trimester malaria. The hazard of miscarriage increased 1.61-fold after an initial first trimester falciparum episode (95% CI 1.32-1.97; p<0.0001), 3.24-fold following falciparum recurrence (2.24-4.68; p<0.0001), and 2.44-fold (1.01-5.88; p=0.0473) following recurrent symptomatic vivax malaria. No difference was noted in miscarriage in first-line falciparum treatments with artemisinin (n=183) versus quinine (n=842; HR 0.78 [95% CI 0.45-1.34]; p=0.3645) or in risk of major congenital malformations (two [2%] of 109 [95% CI 0.22-6.47] versus eight (1%) of 641 [0.54-2.44], respectively). INTERPRETATION: First-trimester falciparum and vivax malaria both increase the risk of miscarriage. We noted no evidence of an increased risk of miscarriage or of major congenital malformations associated with first-line treatment with an artemisinin derivative compared with quinine. In view of the low efficacy of quinine and wide availability of highly effective artemisinin-based combination therapies, it is time to reconsider first-trimester antimalarial treatment recommendations. FUNDING: The Wellcome Trust and The Bill & Melinda Gates Foundation. PMID- 26869379 TI - Mounting evidence for use of artemisinin derivatives for malaria in early pregnancy. PMID- 26869381 TI - Resting energy expenditure in adult patients with Crohn's disease. AB - BACKGROUND & AIMS: Crohn's disease (CD) is a chronic intestinal disorder of unknown etiology involving any section of the gastrointestinal tract often associated with protein-energy malnutrition (PEM). Increased resting energy expenditure (REE) unmatched by adequate dietary intake is amongst the pathogenetic mechanisms proposed for PEM. Aim of this study was to evaluate REE in CD patients receiving or not immuno-suppressive therapy as compared to controls. METHODS: 36 CD patients (22 M and 14 F, age range 18-55 years) clinically stable and without complications since at least 6 month were studied. REE was evaluated by indirect calorimetry and body composition by BIA. Full biochemistry was performed. Patients were divided into two groups: Group 1 (G1 = 12 patients) without and Group 2 (G2 = 24 patients) with immuno-suppressive therapy. RESULTS: The two groups were similar for age, height and BMI whereas significantly differed for weight (G1 vs G2: 56.9 +/- 7.44 vs 62.3 +/- 8.34 kg), fat free mass (FFM: 40.4 +/- 5.73 vs 48.2 +/- 7.06 kg), fat mass (FM: 17.0 +/- 3.55 vs 13.9 +/- 5.54 kg) and phase angle (PA: 5.6 +/- 1.4 vs 6.5 +/- 1.0 degrees ). Serum inflammation parameters were significantly higher in G1 than in G2: hs PCR: 7.76 +/- 14.2 vs 7.16 +/- 13.4 mg/dl; alfa 2-protein: 11.7 +/- 3.69 vs 9.74 +/- 2.08 mg/dl; fibrinogen: 424 +/- 174 vs 334 +/- 118 mg/dl (p < 0.05). REE was higher in G2 vs G1: 1383 +/- 267 vs 1582 +/- 253kcal/die (p < 0.05) both in men: 1579 +/- 314 vs 1640 +/- 203 and women: 1267 +/- 140 vs 1380 +/- 132. Nevertheless, when corrected for FFM, REE resulted higher in G1 than G2 (34.8 +/- 4.89 vs 33.0 +/- 4.35 kcal/kg, p < 0.05) group, also higher compared to our, age and sex matched, control population (REE/FFM: 30.9 +/- 4.5 kcal/kg). CONCLUSIONS: Our preliminary results show that REE when adjusted for FFM is increased in clinically stable CD patients and mildly reduced by immunosuppressive therapy possibly through a direct action on inflammation and on body composition characteristics. PMID- 26869380 TI - Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes. AB - BACKGROUND & AIMS: Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. METHODS: Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. RESULTS: Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P = 0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P = 0.029) and lyso-PL (P = 0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r = 0.388, P = 0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. CONCLUSIONS: In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport. PMID- 26869382 TI - Public health vulnerability to wintertime weather: time-series regression and episode analyses of national mortality and morbidity databases to inform the Cold Weather Plan for England. AB - OBJECTIVES: To inform development of Public Health England's Cold Weather Plan (CWP) by characterizing pre-existing relationships between wintertime weather and mortality and morbidity outcomes, and identification of groups most at risk. STUDY DESIGN: Time-series regression analysis and episode analysis of daily mortality, emergency hospital admissions, and accident and emergency visits for each region of England. METHODS: Seasonally-adjusted Poisson regression models estimating the percent change in daily health events per 1 degrees C fall in temperature or during individual episodes of extreme weather. RESULTS: Adverse cold effects were observed in all regions, with the North East, North West and London having the greatest risk of cold-related mortality. Nationally, there was a 3.44% (95% CI: 3.01, 3.87) increase in all-cause deaths and 0.78% (95% CI: 0.53, 1.04) increase in all-cause emergency admissions for every 1 degrees C drop in temperature below identified thresholds. The very elderly and people with COPD were most at risk from low temperatures. A&E visits for fractures were elevated during heavy snowfall periods, with adults (16-64 years) being the most sensitive age-group. Since even moderately cold days are associated with adverse health effects, by far the greatest health burdens of cold weather fell outside of the alert periods currently used in the CWP. CONCLUSIONS: Our findings indicate that levels 0 ('year round planning') and 1 ('winter preparedness and action') are crucial components of the CWP in comparison to the alerts. Those most vulnerable during winter may vary depending on the type of weather conditions being experienced. Recommendations are made for the CWP. PMID- 26869383 TI - Purification and comparison of heat shock protein 90 (Hsp90) in Candida albicans isolates from Malaysian and Iranian patients and infected mice. AB - OBJECTIVE: The purposes of this study were to purify and compare the concentration ratios of heat shock protein 90 (Hsp90) in clinical isolates of Candida albicans (C. albicans) obtained from Malaysian and Iranian patients and infected mice. MATERIALS AND METHODS: Hsp90 was extracted using glass beads and ultracentrifugation from yeast cells and purified by ion exchange chromatography (DEAE-cellulose) and followed by affinity chromatography (hydroxyapatite). Purity of Hsp90 was controlled by SDS-PAGE and its identification was realized by immunoblotting test. RESULTS: The graphs of ion exchange and affinity chromatography showed one peak in all C. albicans isolates obtained from both Malaysian and Iranian samples, infected mice and under high-thermal (42 degrees C) and low-thermal (25 degrees C) shock. In immunoblotting, the location of Hsp90 fragments was obtained around 47, 75 and 82kDa. The least average concentration ratios of Hsp90 were 0.350 and 0.240mg/g for Malaysian and Iranian isolates at 25 degrees C, respectively, while the highest average concentration ratios of Hsp90 were 3.05 and 2.600mg/g for Malaysian and Iranian isolates at 42 degrees C, respectively. There were differences in the ratio amount of Hsp90 between Malaysian isolates (1.01+/-0.07mg/g) and mice kidneys (1.23+/-0.28mg/g) as well as between Iranian isolates (0.70+/-0.19mg/g) and mice kidneys (1.00+/-0.28mg/g) (P<0.05). CONCLUSION: The results showed differences in all situations tested including Iranian and Malaysian isolates, samples treated with temperatures (25 degrees C or 42 degrees C) and before and after infecting the mice (37 degrees C), indicating higher virulent nature of this yeast species in high temperature in human and animal models. PMID- 26869384 TI - Dietary Approaches to Stop Hypertension Diet and Incidence of Stroke: Results From 2 Prospective Cohorts. AB - BACKGROUND AND PURPOSE: High adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with lower risk of hypertension, the major risk factor for stroke. We examined whether adherence to the DASH diet is inversely associated with the incidence of stroke. METHODS: The study population comprised 74 404 men and women (45-83 years of age), without stroke at baseline, from the Cohort of Swedish Men and the Swedish Mammography Cohort. Diet was assessed with a food-frequency questionnaire. A modified DASH diet score was created based on consumption of vegetables, fruits, legumes and nuts, whole grains, low-fat dairy, red meat and processed meat, and sweetened beverages. Stroke cases were identified through linkage to the Swedish National Patient and Cause of Death Registers. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards regression model. RESULTS: During 882 727 person-years (mean, 11.9 years) of follow-up, 3896 ischemic strokes, 560 intracerebral hemorrhages, and 176 subarachnoid hemorrhages were ascertained. The modified DASH diet score was statistically significantly inversely associated with the risk of ischemic stroke (P for trend=0.002), with a multivariable relative risk of 0.86 (95% confidence interval, 0.78-0.94) for the highest versus the lowest quartile of the score. The modified DASH diet score was nonsignificantly inversely associated with intracerebral hemorrhage (corresponding relative risk=0.81; 95% confidence interval, 0.63-1.05) but was not associated with subarachnoid hemorrhage. CONCLUSIONS: These findings indicate that high adherence to the DASH diet is associated with a reduced risk of ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01127698 and NCT01127711 for the Swedish Mammography Cohort and the Cohort of Swedish Men, respectively. PMID- 26869385 TI - Trends in Age of First-Ever Stroke Following Increased Incidence and Life Expectancy in a Low-Income Chinese Population. AB - BACKGROUND AND PURPOSE: We investigated secular trends in the age of stroke onset and stroke incidence in a low-income population in rural China. METHODS: The study population was recruited from a population-based stroke surveillance study conducted in a township in Tianjin, China, from 1992 to 2014. The trends in mean age and incidence of first-ever stroke were assessed by sex and stroke subtype. Risk factor surveys were conducted in the same population in both 1991 and 2011. RESULTS: A total of 1053 patients experienced first-ever stroke from 1992 to 2014. The mean age of stroke onset in men significantly decreased by 0.28 years annually overall, by 0.56 years for intracerebral hemorrhage, and by 0.22 years for ischemic stroke (P<0.05). However, a similar trend was not observed in women. The age-standardized first-ever stroke incidence in the same population significantly increased across sex and stroke subtypes, increased by 6.3% overall, 5.5% for men, 7.9% for women, 4.6% for intracerebral hemorrhage, and 7.3% for ischemic stroke (P<0.05) during 1992 to 2014. Concurrently, the prevalence of hypertension, diabetes mellitus, obesity, current smoking, and alcohol consumption increased significantly in young and middle-aged adults from 1991 to 2011. CONCLUSIONS: The age of stroke onset tends to be younger among low income population in China after the dramatic increased incidence of stroke during the gradual extension of life expectancy of population in China. These findings suggested that stroke burden will continue to increase in the long time, unless the risk factors in low-income populations are effectively controlled. PMID- 26869386 TI - Risk Score for Neurological Complications After Endovascular Treatment of Unruptured Intracranial Aneurysms. AB - BACKGROUND AND PURPOSE: Procedure-related neurological complications are common after endovascular treatment of unruptured intracranial aneurysms. We aimed to develop a score to quantify individual patient risk. METHODS: We retrospectively analyzed consecutive patients who underwent endovascular treatment for unruptured intracranial aneurysms between January 2012 and September 2015. After excluding those who lost to follow-up and those with fusiform unruptured intracranial aneurysms, included patients were randomly divided into a derivation group (60%) and a validation group (40%). A neurological complication was defined as any transient or permanent increase in the modified Rankin Scale score after aneurysm embolization. A risk score for neurological complications was derived from multivariable logistic regression analyses in the derivation group and validated in the validation group. RESULTS: Overall, 1060 patients were included (636 in the derivation group and 424 in the validation group). The incidence of neurological complications was 5.5% (95% confidence interval, 3.8%-7.4%). A 3 point risk score (S-C-C) was derived to predict neurological complications (size [>=10 mm=1], core areas [yes=1], and cerebral ischemic comorbidity [yes=1]). The incidence of neurological complications varied from 2.2% in 0-point patients to 25.0% in 3-point patients. The score demonstrated significant discrimination (C statistic, 0.714; 95% confidence interval, 0.624-0.804) and calibration (McFadden R(2), 0.102) in the derivation group. Excellent prediction, discrimination, and calibration properties were reproduced in the validation group. CONCLUSIONS: One in 20 patients will develop neurological complications after endovascular treatment of unruptured intracranial aneurysms. The S-C-C score may be useful for predicting these adverse outcomes based on variables in daily practice. PMID- 26869389 TI - Elevated CO2 as a driver of global dryland greening. AB - While recent findings based on satellite records indicate a positive trend in vegetation greenness over global drylands, the reasons remain elusive. We hypothesize that enhanced levels of atmospheric CO2 play an important role in the observed greening through the CO2 effect on plant water savings and consequent available soil water increases. Meta-analytic techniques were used to compare soil water content under ambient and elevated CO2 treatments across a range of climate regimes, vegetation types, soil textures and land management practices. Based on 1705 field measurements from 21 distinct sites, a consistent and statistically significant increase in the availability of soil water (11%) was observed under elevated CO2 treatments in both drylands and non-drylands, with a statistically stronger response over drylands (17% vs. 9%). Given the inherent water limitation in drylands, it is suggested that the additional soil water availability is a likely driver of observed increases in vegetation greenness. PMID- 26869387 TI - Role of Lipocalin-2 in Thrombin-Induced Brain Injury. AB - BACKGROUND AND PURPOSE: Thrombin and lipocalin-2 (LCN2) contribute to intracerebral hemorrhage-induced brain injury. Thrombin-induced brain damage is partially through a thrombin receptor, protease-activated receptor-1. LCN2 is involved in cellular iron transport and neuroinflammation. This study investigated the role of LCN2 in thrombin-induced brain injury. METHODS: There were 3 parts in this study. First, male adult C57BL/6 wild-type or LCN2 knockout (LCN2 KO) mice had an intracaudate injection of thrombin (0.4 U) or saline. Second, LCN2 KO mice had an injection of thrombin (0.4 U) with recombinant mouse LCN2 protein (1 MUg) into the right caudate. Third, protease-activated receptor-1 KO or wild-type mice had an intracaudate injection of thrombin or saline. All mice had T2-weighted magnetic resonance imaging and behavioral tests. Brains were used for histology, immunohistochemistry, and Western blotting. RESULTS: Intracerebral thrombin injection caused LCN2 upregulation and brain injury in mice. Thrombin-induced brain swelling, blood-brain barrier disruption, neuronal death, and neurological deficits were markedly less in LCN2 KO mice (P<0.05) and were exacerbated by exogenous LCN2 coinjection. In addition, thrombin injection resulted in less LCN2 expression and brain injury in protease-activated receptor 1 KO mice. CONCLUSIONS: Thrombin upregulates LCN2 through protease-activated receptor-1 activation and causes brain damage. PMID- 26869390 TI - Segregation of "isotope" particles within colloidal molecules. AB - Clusters of spherical particles are called "colloidal molecules" because they adopt structures that resemble those of true molecules. In this analogy, the particles are the atoms, the attractive interactions between them are bonds, and the different structures that appear in equilibrium are isomers. We take this analogy a step further by doping colloidal molecules with colloidal "isotopes," particles that have the same size but different bonding energies from the other particles in the system. Our molecules are two-dimensional clusters consisting of polystyrene and silica microspheres held together by depletion interactions. Using a combination of optical microscopy and particle tracking, we examine an ensemble of 4- and 5-particle molecules at different isotope ratios. We find that the isotopes tend to segregate to particular positions in the various isomers. We explain these findings using a statistical mechanical model that accounts for the rotational entropy of the isomers and the different interaction potentials between the different types of particles. The model shows how to optimize the yield of any particular isomer, so as to put the isotopes in desired locations. Our experiments and models show that even in systems of particles with isotropic interactions, the structures of self-assembled molecules can in principle be controlled to a surprisingly high extent. PMID- 26869388 TI - Salusin-beta as a powerful endogenous antidipsogenic neuropeptide. AB - Salusin-beta is an endogenous parasympathomimetic peptide, predominantly localized to the hypothalamus and posterior pituitary. Subcutaneously administered salusin-beta (50 nmol/mouse) significantly increased water intake but did not affect locomotor activity or food intake. The salusin-beta-induced increase in water intake was completely abrogated by pretreatment with muscarinic antagonist, atropine sulphate. In contrast, intracerebroventricular injection of salusin-beta, at lower doses (10-100 fmol/mouse) caused a long-lasting decrease in water intake and locomotor activity throughout the entire dark phase of the diurnal cycle. Pre-injection of intracerebroventricular anti-salusin-beta IgG completely abrogated the central salusin-beta mediated suppression of water intake and locomotor activity. These results demonstrate contrasting actions of salusin-beta in the control of water intake via the central and peripheral systems and highlight it as a potent endogenous antidipsogenic neuropeptide. PMID- 26869391 TI - Fructose consumption induces hypomethylation of hepatic mitochondrial DNA in rats. AB - AIMS: Fructose may play a crucial role in the pathogenesis of metabolic syndrome (MetS). However, the pathogenic mechanism of the fructose-induced MetS has not yet been investigated fully. Recently, several reports have investigated the association between mitochondrial DNA (mtDNA) and MetS. We examined the effect of fructose-rich diets on mtDNA content, transcription, and epigenetic changes. MAIN METHODS: Four-week-old male Sprague-Dawley rats were offered a 20% fructose solution for 14weeks. We quantified mRNAs for hepatic mitochondrial genes and analyzed the mtDNA methylation (5-mC and 5-hmC) levels using ELISA kits. KEY FINDINGS: Histological analysis revealed non-alcoholic fatty liver disease (NAFLD) in fructose-fed rats. Hepatic mtDNA content and transcription were higher in fructose-fed rats than in the control group. Global hypomethylation of mtDNA was also observed in fructose-fed rats. SIGNIFICANCE: We showed that fructose consumption stimulates hepatic mtDNA-encoded gene expression. This phenomenon might be due to epigenetic changes in mtDNA. Fructose-induced mitochondrial epigenetic changes appear to be a novel mechanism underlying the pathology of MetS and NAFLD. PMID- 26869392 TI - Carotid Plaque Characterization, Stenosis, and Intima-Media Thickness According to Age and Gender in a Large Registry Cohort. AB - Carotid intima-media thickness (CIMT) is a well-established predictor of cardiovascular disease events. Not well described, however, is the prevalence of plaque and stenosis severity and how this varies according to extent of CIMT, age, and gender. We evaluated the extent of carotid plaque and stenosis severity according to CIMT, age, and gender in a large CIMT screening registry. We studied 9,347 women and 12,676 men (n = 22,023) who received carotid ultrasound scans. The presence and severity of both carotid plaque and stenosis was compared according to extent of CIMT (>=1 mm vs <1 mm), age, and gender using the chi square test of proportions. Among those aged <45 to >=80 years, the prevalence of CIMT >=1 mm ranged from 0.13% to 29.3% in women and 0.6% to 40.1% in men, stenosis >=50% from 0.1% to 14.9% in women and 0.1% to 13.2% in men, and mixed and/or soft plaque from 7.1% to 66.5% in women, and 9.2% to 65.8% in men (all p <0.001 across age groups). Even when CIMT levels were <1 mm, >30% of patients demonstrated mixed or soft plaque potentially prone to rupture. Of those with CIMT >=1 mm, more than 70% had such mixed or soft plaque and more than 40% demonstrated stenoses of 30% or greater. In conclusion, we describe in a large CIMT registry study a substantial age-related increase in both men and women of increased CIMT, plaque presence, and severity, and stenosis. Even in those with normal CIMT, mixed or soft plaque was common, further demonstrating the value in assessing for plaque when doing carotid ultrasound. PMID- 26869393 TI - Impact of Genotype on the Occurrence of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy. AB - Genes associated with hypertrophic cardiomyopathy (HC) are not uniformly expressed in the atrial myocardium. Whether this may impact susceptibility to atrial fibrillation (AF) is unresolved. To analyze the prevalence and clinical correlates of AF in relation to genotype in a large HC cohort, prevalence and clinical profile of AF were assessed in 237 patients with HC, followed for 14 +/- 10 years. Patients were divided into 3 genetic subgroups: (1) MYBPC3 (58%), (2) MYH7 (28%), and (3) "other genotypes" (14%; comprising TNNT2, TNNI3, TPM1, MYL2, complex genotypes, Z-line, and E-C coupling genes). Left atrial size was similar in the 3 subsets. AF occurred in 74 patients with HC (31%), with no difference among groups (31% in MYBPC3, 37% in MYH7 and 18% in other genotypes, p = 0.15), paroxysmal/persistent AF (12%, 18%, and 12%, respectively; p = 0.53), paroxysmal/persistent evolved to permanent (12%, 12%, and 3%, p = 0.36) or permanent AF (7%, 7%, and 3%, p = 0.82). Age at AF onset was younger in the group with other genotypes (37 +/- 10 years) compared to the first 2 groups (53 +/- 14 and 51 +/- 17, respectively; p = 0.05) because of early onset associated with complex genotypes and a specific JPH2 mutation associated with abnormal intracellular calcium handling. At multivariate analysis, independent predictors of AF were atrial diameter (p <=0.05) and age at diagnosis (p = 0.09), but not genetic subtype (p = 0.35). In conclusion, in patients with HC, genetic testing cannot be used in clinical decision making with regard to management strategies for AF. Genotype is not predictive of onset or severity of AF, which appears rather driven by hemodynamic determinants of atrial dilatation. Exceptions are represented by rare genes suggesting specific molecular pathways for AF in genetic cardiomyopathies. PMID- 26869394 TI - Autonomic Nervous System Function in Patients With Takotsubo Syndrome. PMID- 26869395 TI - The ability to cross the blood-cerebrospinal fluid barrier is a generic property of acute lymphoblastic leukemia blasts. AB - Prevention of central nervous system (CNS) relapse is critical for cure of childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Despite this, mechanisms of CNS infiltration are poorly understood, and the timing, frequency, and properties of BCP-ALL blasts entering the CNS compartment are unknown. We investigated the CNS-engrafting potential of BCP-ALL cells xenotransplanted into immunodeficient NOD.Cg- ITALIC! Prkdc (ITALIC! scid) ITALIC! Il2rg (ITALIC! tm1Wjl)/SzJ mice. CNS engraftment was seen in 23 of 29 diagnostic samples (79%): 2 of 2 from patients with overt CNS disease and 21 of 27 from patients thought to be CNS negative by diagnostic lumbar puncture. Histologic findings mimic human pathology and demonstrate that leukemic cells transit the blood-cerebrospinal fluid barrier situated close to the dural sinuses, the site of recently discovered CNS lymphatics. Retrieval of blasts from the CNS showed no evidence for chemokine receptor-mediated selective trafficking. The high frequency of infiltration and lack of selective trafficking led us to postulate that CNS tropism is a generic property of leukemic cells. To test this, we performed serial dilution experiments which showed CNS engraftment in 5 of 6 mice after transplant of as few as 10 leukemic cells. Clonal tracking techniques confirmed the polyclonal nature of CNS-infiltrating cells, with multiple clones engrafting in both the CNS and periphery. Overall, these findings suggest that subclinical seeding of the CNS is likely to be present in most BCP-ALL patients at original diagnosis, and efforts to prevent CNS relapse should concentrate on effective eradication of disease from this site rather than targeting entry mechanisms. PMID- 26869396 TI - Metastatic nasopharyngeal carcinoma with extensive Langerhans' cell reaction and its significance: a case initially diagnosed by fine needle aspiration cytology. PMID- 26869397 TI - Generation of recombinant rabies viruses encoding NanoLuc luciferase for antiviral activity assays. AB - Rabies is an invariably fatal disease caused by Rabies virus (RABV), a member of the family Rhabdoviridae, genus Lyssavirus. Once central nervous infection occurs and symptoms develop, the case fatality rate approaches 100% despite availability of post-exposure prophylaxis. Therefore, new antiviral therapies for rabies are urgently required. Antivirals which can inhibit virus replication can be identified through screening of small compounds, however, as RABV infection does not generate easily discernible cytopathic effects in vitro, cell viability assays may not be feasible to observe antiviral activity of small compounds against RABV. In this study, recombinant RABVs (rRABVs) encoding NanoLuc luciferase (NanoLuc) were generated to facilitate the screening of small compound libraries. NanoLuc expression was confirmed in single-step growth cures of virus infection and showed that the rRABVs were capable of viral replication without decrease of luciferase activity through ten serial passages. Furthermore, the rRABVs were able to quantify the antiviral activity of the nucleoside analogue ribavirin against RABV in vitro. These findings confirm the potential of the rRABV encoding NanoLuc system to facilitate screening of small compounds to inhibit RABV infection. PMID- 26869398 TI - Solvent-shift strategy to identify suitable polymers to inhibit humidity-induced solid-state crystallization of lacidipine amorphous solid dispersions. AB - The solvent-shift strategy was used to identify appropriate polymers that inhibit humidity-induced solid-state crystallization of amorphous solid dispersions (ASDs). Lacidipine with the polymers, PVP-K30, HPMC-E5 or Soluplus, were combined to form amorphous solid dispersions prepared by solvent evaporation. The formulations were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT IR) and were subjected to in vitro dissolution testing. The moisture had a significant impact on the amount dissolved for the solid dispersions. Molecular docking studies established that hydrogen bonding was critical for the stabilization of the solid dispersions. The rank order of the binding energy of the drug-polymer association was Soluplus (-6.21 kcal/mol)>HPMC-E5 (-3.21 kcal/mol)>PVP-K30 (-2.31 kcal/mol). PVP-K30 had the highest water uptake among the polymers, as did ASD system of lacidipine-PVP-K30 ASDs. In the Soluplus ASDs, with its strong drug-polymer interactions and low water uptake, moisture-induced solid-state crystallization was not observed. PMID- 26869399 TI - Dipicrylamine Modulates GABArho1 Receptors through Interactions with Residues in the TM4 and Cys-Loop Domains. AB - Dipicrylamine (DPA) is a commonly used acceptor agent in Forster resonance energy transfer experiments that allows the study of high-frequency neuronal activity in the optical monitoring of voltage in living cells. However, DPA potently antagonizes GABAA receptors that contain alpha1 and beta2 subunits by a mechanism which is not clearly understood. In this work, we aimed to determine whether DPA modulation is a general phenomenon of Cys-loop ligand-gated ion channels (LGICs), and whether this modulation depends on particular amino acid residues. For this, we studied the effects of DPA on human homomeric GABArho1, alpha7 nicotinic, and 5-HT3A serotonin receptors expressed in Xenopus oocytes. Our results indicate that DPA is an allosteric modulator of GABArho1 receptors with an IC50 of 1.6 uM, an enhancer of alpha7 nicotinic receptors at relatively high concentrations of DPA, and has little, if any, effect on 5-HT3A receptors. DPA antagonism of GABArho1 was strongly enhanced by preincubation, was slightly voltage-dependent, and its washout was accelerated by bovine serum albumin. These results indicate that DPA modulation is not a general phenomenon of LGICs, and structural differences between receptors may account for disparities in DPA effects. In silico modeling of DPA docking to GABArho1, alpha7 nicotinic, and 5-HT3A receptors suggests that a hydrophobic pocket within the Cys-loop and the M4 segment in GABArho1, located at the extracellular/membrane interface, facilitates the interaction with DPA that leads to inhibition of the receptor. Functional examinations of mutant receptors support the involvement of the M4 segment in the allosteric modulation of GABArho1 by DPA. PMID- 26869400 TI - Voltage-Independent Inhibition of the Tetrodotoxin-Sensitive Sodium Currents by Oxotremorine and Angiotensin II in Rat Sympathetic Neurons. AB - Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these currents can be readily inhibited through a signaling pathway mediated by G proteins and phospholipase C (PLC) beta1. This inhibition is slowly established, pertussis toxin-insensitive, partially reversed within tens of seconds after oxo M washout, and not relieved by a strong depolarization, suggesting a voltage insensitive mechanism of inhibition. Specificity of the M1 receptor was tested by the MT-7 toxin. Activation and inactivation curves showed no shift in the voltage dependency under the inhibition by oxo-M. This inhibition is blocked by a PLC inhibitor (U73122, 1-(6-{[(17beta)-3-Methoxyestra-1,3,5(10)-trien-17 yl]amino}hexyl)-1H-pyrrole-2,5-dione), and recovery from inhibition is prevented by wortmannin, a PI3/4 kinase inhibitor. Hence, the pathway involves Gq/11 and is mediated by a diffusible second messenger. Oxo-M inhibition is occluded by screening phosphatidylinositol 4,5-bisphosphate (PIP2)-negative charges with poly l-lysine and prevented by intracellular dialysis with a PIP2 analog. In addition, bisindolylmaleimide I, a specific ATP-competitive protein kinase C (PKC) inhibitor, rules out that this inhibition may be mediated by this protein kinase. Furthermore, oxo-M-induced suppression of Na(+) currents remains unchanged when neurons are treated with calphostin C, a PKC inhibitor that targets the diacylglycerol-binding site of the kinase. These results support a general mechanism of Na(+) current inhibition that is widely present in excitable cells through modulation of ion channels by specific G protein-coupled receptors. PMID- 26869401 TI - Editorial: guidelines for oral and maxillofacial radiology. PMID- 26869404 TI - AREG and EREG as Predictive Biomarkers for RAS Wild-Type Colorectal Cancer Treated With Panitumumab: A Fresh Approach to an Old Puzzle. PMID- 26869405 TI - Editorial. PMID- 26869403 TI - Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in a streptozotocin-induced diabetes rat model. AB - Ginsenoside Rg1 has been demonstrated to have cardiovascular protective effects. However, whether the cardioprotective effects of ginsenoside Rg1 are mediated by endoplasmic reticulum (ER) stress-induced apoptosis remain unclear. In this study, among 80 male Wistar rats, 15 rats were randomly selected as controls; the remaining 65 rats received a diet rich in fat and sugar content for 4 weeks, followed by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) to establish a diabetes model. Seven days after STZ injection, 10 rats were randomly selected as diabetic model (DM) controls, 45 eligible diabetic rats were randomized to three treatment groups and administered ginsenoside Rg1 in a dosage of 10, 15 or 20 mg/kg/day, respectively. After 12 weeks of treatment, rats were killed and serum samples obtained to determine cardiac troponin (cTn)-I. Myocardial tissues were harvested for morphological analysis to detect myocardial cell apoptosis, and to analyse protein expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and Caspase-12. Treatment with ginsenoside Rg1 (10-20 mg/kg) significantly reduced serum cTnI levels compared with DM control group (all P < 0.01). Ginsenoside Rg1 (15 and 20 mg/kg) significantly reduced the percentage of apoptotic myocardial cells and improved the parameters of cardiac function. Haematoxylin and eosin and Masson staining indicated that ginsenoside Rg1 could attenuate myocardial lesions and myocardial collagen volume fraction. Additionally, ginsenoside Rg1 significantly reduced GRP78, CHOP, and cleaved Caspase-12 protein expression in a dose-dependent manner. These findings suggest that ginsenoside Rg1 appeared to ameliorate diabetic cardiomyopathy by inhibiting ER stress-induced apoptosis in diabetic rats. PMID- 26869406 TI - Physical and Chemical Stability of Antibody Drug Conjugates: Current Status. AB - Antibody drug conjugates (ADCs) are an emerging class of chemotherapeutic cancer treatment agents that combine the targeting specificity of antibodies with the efficient cell-killing potential of cytotoxic drugs. Unlike their protein and small-molecule therapeutic counterparts, the stability and degradation properties of ADCs are relatively unknown. Theoretically, ADC stability could be governed by properties and processes stemming from both the antibody and the linker-toxin chemistry. Recently, systematic studies of intrinsic ADC molecule stability have been presented in the primary literature. As there are burgeoning industrial and academic efforts aimed at developing optimized conjugation chemistries and antibody engineering approaches for next-generation ADCs, it is important to capture the current state of understanding of ADC stability. In this minireview, we discuss aspects of physical and chemical stability of ADCs gathered from a survey of the literature and illustrate how investigations into stability enable the development of more effective ADC molecules for the future. PMID- 26869407 TI - Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier. AB - Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food and Drug Administration approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain barrier are useful tools to investigate the effects of induced ischemia under controlled conditions. In the present mini review, we aim to give a brief overview of the in vitro models of ischemia. Special focus is given to the expression of uptake and efflux transport pathways in the ischemic and postischemic endothelium. Finally, we will point toward future challenges within the field of in vitro models of brain ischemia. PMID- 26869409 TI - Immunogenicity of Therapeutic Protein Aggregates. AB - Therapeutic proteins have a propensity for aggregation during manufacturing, shipping, and storage. The presence of aggregates in protein drug products can induce adverse immune responses in patients that may affect safety and efficacy, and so it is of concern to both manufacturers and regulatory agencies. In this vein, there is a lack of understanding of the physicochemical determinants of immunological responses and a lack of standardized analytical methods to survey the molecular properties of aggregates associated with immune activation. In this review, we provide an overview of the basic immune mechanisms in the context of interactions with protein aggregates. We then critically examine the literature with emphasis on the underlying immune mechanisms as they relate to aggregate properties. Finally, we highlight the gaps in our current understanding of this issue and offer recommendations for future research. PMID- 26869410 TI - Explication of Definitional Description and Empirical Use of Fraction of Orally Administered Drugs Absorbed From the Intestine (Fa) and Intestinal Availability (Fg): Effect of P-glycoprotein and CYP3A on Fa and Fg. AB - Conventionally, it is believed that the fraction of orally administered drugs absorbed from the intestine (Fa) and intestinal availability (Fg) are independently determined by the apical membrane permeation and intestinal metabolism, respectively. However, the validity of this belief has not been well discussed, and Fa and Fg are often used without careful definition. In this review, Fa and Fg are mathematically described based on their definitions under the linear kinetics of metabolism and transport. Even considering with different models, intestinal metabolic enzymes such as cytochrome P450 3A affected both Fa and Fg, whereas apical efflux transporters including P-glycoprotein had no influence on Fg at least under the linear condition. To determine whether Fa and Fg calculated using different clinical methods are identical, empirical Fa and Fg were mathematically described based on "feces method" and "grapefruit juice method" and compared with their definitions. Fa and Fg obtained by the feces method corresponded with their definitions whereas the grapefruit juice method provided smaller Fa and larger Fg particularly for dual substrates of P glycoprotein and cytochrome P450 3A with low membrane permeability. Our analyses suggest that the definitions and calculation methods of Fa and Fg should be considered when we intend to separately determine these values. PMID- 26869408 TI - Toward Carbon Monoxide-Based Therapeutics: Critical Drug Delivery and Developability Issues. AB - Carbon monoxide (CO) is an intrinsic signaling molecule with importance on par with that of nitric oxide. During the past decade, pharmacologic studies have amply demonstrated the therapeutic potential of carbon monoxide. However, such studies were mostly based on CO inhalation and metal-based CO-releasing molecules. The field is now at the stage that a major effort is needed to develop pharmaceutically acceptable forms of CO for delivery via various routes such as oral, injection, infusion, or topical applications. This review examines the state of the art, discusses the existing hurdles to overcome, and proposes developmental strategies necessary to address remaining drug delivery issues. PMID- 26869412 TI - PEGylation of Biopharmaceuticals: A Review of Chemistry and Nonclinical Safety Information of Approved Drugs. AB - Modification of biopharmaceutical molecules by covalent conjugation of polyethylene glycol (PEG) molecules is known to enhance pharmacologic and pharmaceutical properties of proteins and other large molecules and has been used successfully in 12 approved drugs. Both linear and branched-chain PEG reagents with molecular sizes of up to 40 kDa have been used with a variety of different PEG derivatives with different linker chemistries. This review describes the properties of PEG itself, the history and evolution of PEGylation chemistry, and provides examples of PEGylated drugs with an established medical history. A trend toward the use of complex PEG architectures and larger PEG polymers, but with very pure and well-characterized PEG reagents is described. Nonclinical toxicology findings related to PEG in approved PEGylated biopharmaceuticals are summarized. The effect attributed to the PEG part of the molecules as observed in 5 of the 12 marketed products was cellular vacuolation seen microscopically mainly in phagocytic cells which is likely related to their biological function to absorb and remove particles and macromolecules from blood and tissues. Experience with marketed PEGylated products indicates that adverse effects in toxicology studies are usually related to the active part of the drug but not to the PEG moiety. PMID- 26869413 TI - Why Does the Intestine Lack Basolateral Efflux Transporters for Cationic Compounds? A Provocative Hypothesis. AB - Transport proteins in intestinal epithelial cells facilitate absorption of nutrients/compounds that are organic anions, cations, and zwitterions. For two decades, we have studied intestinal absorption and transport of hydrophilic ionic compounds, with specific focus on transport properties of organic cations and their interactions with intestinal transporters and tight junction proteins. Our data reveal how complex interactions between a compound and transporters in intestinal apical/basolateral (BL) membranes and tight junction proteins define oral absorption, and that the BL membrane lacks an efflux transporter that can transport positively charged compounds. Based on our investigations of transport mechanisms of zwitterionic, anionic, and cationic compounds, we postulate that physicochemical properties of these ionic species, in relation to the intestinal micro pH environment, have exerted evolutionary pressure for development of transporters that can handle apical uptake/efflux of all 3 ionic species and BL efflux of anions and zwitterions, but such evolutionary pressure is lacking for development of a BL efflux transporter for cationic compounds. This review provides an overview of intestinal uptake/efflux transporters and describes our studies on intestinal transport of cationic, anionic, and zwitterionic drugs that led to hypothesize that there are no cation-selective BL efflux transporters in the intestine. PMID- 26869414 TI - N+1 Engineering of an Aspartate Isomerization Hotspot in the Complementarity Determining Region of a Monoclonal Antibody. AB - Aspartate (Asp) isomerization is a common degradation pathway and a potential critical quality attribute that needs to be well characterized during the optimization and development of therapeutic antibodies. A putative Asp-serine (Ser) isomerization motif was identified in the complementarity-determining region of a humanized monoclonal antibody and shown to be a developability risk using accelerated stability analyses. To address this issue, we explored different antibody engineering strategies. Direct engineering of the Asp residue resulted in a greater than 5* loss of antigen-binding affinity and bioactivity, indicating a critical role for this residue. In contrast, rational engineering of the Ser residue at the n+1 position had a negligible impact on antigen binding affinity and bioactivity compared with the parent molecule. Furthermore, the n+1 engineering strategy effectively eliminated Asp isomerization as determined by accelerated stability analysis. This outcome affirms that the rate of Asp isomerization is strongly dependent on the identity of the n+1 residue. This report highlights a systematic antibody engineering strategy for mitigating an Asp isomerization developability risk during lead optimization. PMID- 26869415 TI - No Touching! Abrasion of Adsorbed Protein Is the Root Cause of Subvisible Particle Formation During Stirring. AB - This study addressed the effect of contact sliding during stirring of a monoclonal antibody solution on protein aggregation, in particular, in the nanometer and micrometer size range. An overhead stirring set-up was designed in which the presence and magnitude of the contact between the stir bar and the container could be manipulated. A solution of 0.1 mg/mL of a monoclonal antibody (IgG) in phosphate buffered saline was stirred at 300 rpm at room temperature. At different time points, samples were taken and analyzed by nanoparticle tracking analysis, flow imaging microscopy, and size-exclusion chromatography. In contrast to non-contact-stirred and unstirred samples, the contact-stirred sample contained several-fold more particles and showed a significant loss of monomer. No increase in oligomer content was detected. The number of particles formed was proportional to the contact area and the magnitude of the normal pressure between the stir bar and the glass container. Extrinsic 9-(2,2-dicyanovinyl) julolidine fluorescence indicated a conformational change for contact-stirred protein samples. Presence of polysorbate 20 inhibited the formation of micron-sized aggregates. We suggest a model in which abrasion of the potentially destabilized, adsorbed protein leads to aggregation and renewal of the surface for adsorption of a fresh protein layer. PMID- 26869411 TI - Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug Induced Liver Injury. AB - Sandwich-cultured hepatocytes (SCH) are metabolically competent and have proper localization of basolateral and canalicular transporters with functional bile networks. Therefore, this cellular model is a unique tool that can be used to estimate biliary excretion of compounds. SCH have been used widely to assess hepatobiliary disposition of endogenous and exogenous compounds and metabolites. Mechanistic modeling based on SCH data enables estimation of metabolic and transporter-mediated clearances, which can be used to construct physiologically based pharmacokinetic models for prediction of drug disposition and drug-drug interactions in humans. In addition to pharmacokinetic studies, SCH also have been used to study cytotoxicity and perturbation of biological processes by drugs and hepatically generated metabolites. Human SCH can provide mechanistic insights underlying clinical drug-induced liver injury (DILI). In addition, data generated in SCH can be integrated into systems pharmacology models to predict potential DILI in humans. In this review, applications of SCH in studying hepatobiliary drug disposition and bile acid-mediated DILI are discussed. An example is presented to show how data generated in the SCH model were used to establish a quantitative relationship between intracellular bile acids and cytotoxicity, and how this information was incorporated into a systems pharmacology model for DILI prediction. PMID- 26869416 TI - Addition of Monovalent Electrolytes to Improve Storage Stability of Freeze-Dried Protein Formulations. AB - This study investigates the effect of low levels of electrolytes on storage stability in freeze-dried sucrose-based protein formulations. Both bovine serum albumin and recombinant human serum albumin were freeze dried with sucrose and alkali halides (LiCl, NaCl, KCl, RbCl, and CsCl) at selected low levels. All formulations were stored at 50 degrees C and 65 degrees C up to 2 months and then assayed for protein aggregation. The data demonstrate that low levels of LiCl and NaCl enhance stability. No obvious correlations with either protein secondary structure or global dynamics (structural relaxation time) were found. However, good correlations were found between stability and both free-volume hole size via positron annihilation lifetime spectroscopy (PALS) and fast dynamics by neutron scattering. Volume changes on mixing and the partial molal volume of salt were also studied in an effort to detect decreases in free volume. These data did not support the hypothesis that reduction in free volume was the primary mechanism for salt-induced stabilization. Finally, a positive effect of postlyophilization annealing on stability was demonstrated. In summary, we find that small amounts of LiCl and NaCl significantly stabilize these proteins, which is a result at variance with conventional formulation wisdom. PMID- 26869417 TI - Quality and Batch-to-Batch Consistency of Original and Biosimilar Epoetin Products. AB - Comprehensive physicochemical characterization and biological assays are essential parts in assessing quality attributes of biologicals. Here, we compared the quality of different marketed recombinant human erythropoietin (epoetin) products: originators, Eprex and NeoRecormon as well as 2 biosimilars, Retacrit and Binocrit. In addition, assessment of batch-to-batch variability was included by collecting 2 or more batches of each product. Common assays which included sodium dodecyl sulfate-polyacrylamide gel electrophoresis, high-performance size exclusion chromatography, asymmetrical flow field-flow fractionation, capillary zone electrophoresis, and potency testing were used. Of the tested products and among batches of single products, variations in epoetin content, isoform profiles, and potency were found. Ultimately, this study demonstrated the high quality of epoetin products with some degree of variation among products and batches, confirming the "similar but not identical" paradigm of biologicals. PMID- 26869418 TI - Characterization of Sizes of Aggregates of Insulin Analogs and the Conformations of the Constituent Protein Molecules: A Concomitant Dynamic Light Scattering and Raman Spectroscopy Study. AB - To generate aggregates, 3 insulin analogs, lispro, aspart, and glulisine, were incubated without phenolic preservatives for 30 days at 37 degrees C. As a function of incubation time, aggregation was quantified with size exclusion chromatography, and the sizes of aggregates and the conformations of the constituent molecules were characterized with concomitant dynamic light scattering and Raman spectroscopy. During incubation, lispro was progressively converted into soluble aggregates with hydrodynamic diameters of circa 15 nm, and 95% of the native protein had aggregated at day 30. Raman spectroscopy documented that aggregation resulted in conversion of a large fraction of native alpha helix into nonnative beta sheet structure and a distortion of disulfide bonds. In contrast, for aspart and glulisine only 20% of the native proteins aggregated after 30 days, and minimal structural perturbations were detected. In addition, consistent with the relative aggregation rates during isothermal incubation, Raman spectroscopy showed that during heating the onset temperature for secondary structural perturbations of lispro occurred 7 degrees C-10 degrees C lower than those for aspart or glulisine. Overall the results of this study demonstrated that-as in the case during formation of amyloid fibrils from insulin-formation of soluble aggregates of lispro resulted in a high level of conversion of alpha helix into beta sheet. PMID- 26869419 TI - Production, Characterization, and Biological Evaluation of Well-Defined IgG1 Fc Glycoforms as a Model System for Biosimilarity Analysis. AB - Four different well-defined IgG1 Fc glycoforms are proposed as a model system to examine important biological and physicochemical features for protein drug biosimilar analyses. The IgG1 Fc glycoforms were produced by yeast expression combined with in vitro enzymatic synthesis as a series of sequentially truncated high-mannose IgG1 Fc glycoforms with an anticipated range of biological activity and structural stability. Initial characterization with mass spectrometry, SDS PAGE, size exclusion HPLC, and capillary isoelectric focusing confirmed that the glycoproteins are overall highly similar with the only major difference being glycosylation state. Binding to the activating Fc receptor, FcgammaRIIIa was used to evaluate the potential biological activity of the IgG1 Fc glycoproteins. Two complementary methods using biolayer interferometry, 1 with protein G-immobilized IgG1 Fc and the other with streptavidin-immobilized FcgammaRIIIa, were developed to assess FcgammaRIIIa affinity in kinetic binding studies. The high-mannose IgG1 Fc and Man5-IgG1 Fc glycoforms were highly similar to one another with high affinity for FcgammaRIIIa, whereas GlcNAc-Fc had weak affinity, and the nonglycosylated N297Q-Fc had no measurable affinity for FcgammaRIIIa. These 4 IgG1 Fc glycoforms were also evaluated in terms of physical and chemical stability profiles and then used as a model system to mathematically assess overall biosimilarity, as described in a series of companion articles. PMID- 26869421 TI - Correlating the Impact of Well-Defined Oligosaccharide Structures on Physical Stability Profiles of IgG1-Fc Glycoforms. AB - As part of a series of articles in this special issue describing 4 well-defined IgG1-Fc glycoforms as a model system for biosimilarity analysis (high mannose-Fc, Man5-Fc, GlcNAc-Fc and N297Q-Fc aglycosylated), the focus of this work is comparisons of their physical properties. A trend of decreasing apparent solubility (thermodynamic activity) by polyethylene glycol precipitation (pH 4.5, 6.0) and lower conformational stability by differential scanning calorimetry (pH 4.5) was observed with reducing size of the N297-linked oligosaccharide structures. Using multiple high-throughput biophysical techniques, the physical stability of the Fc glycoproteins was then measured in 2 formulations (NaCl and sucrose) across a wide range of temperatures (10 degrees C-90 degrees C) and pH (4.0-7.5) conditions. The data sets were used to construct 3-index empirical phase diagrams and radar charts to visualize the regions of protein structural stability. Each glycoform showed improved stability in the sucrose (vs. salt) formulation. The HM-Fc and Man5-Fc displayed the highest relative stability, followed by GlcNAc-Fc, with N297Q-Fc being the least stable. Thus, the overall physical stability profiles of the 4 IgG1-Fc glycoforms also show a correlation with oligosaccharide structure. These data sets are used to develop a mathematical model for biosimilarity analysis (as described in a companion article by Kim et al. in this issue). PMID- 26869420 TI - Comparative Evaluation of the Chemical Stability of 4 Well-Defined Immunoglobulin G1-Fc Glycoforms. AB - As part of a series of articles in this special issue evaluating model IgG1-Fc glycoforms for biosimilarity analysis, 3 well-defined IgG1-Fc glycoforms (high mannose-Fc, Man5-Fc, and N-acetylglucosamine-Fc) and a nonglycosylated Fc protein (N297Q-Fc) were examined in this work to elucidate chemical degradation pathways. The 4 proteins underwent a combination of accelerated thermal stability studies and 4 independent forced degradation studies (UV light, metal-catalyzed oxidation, peroxyl radicals, and hydrogen peroxide) at pH 6.0. Our results highlight chemical degradations at Asn315, Met428, Trp277, and Trp313. A cross comparison of the different Fc glycoforms, stress conditions, and the observed chemical reactions revealed that both the deamidation of Asn315 and the transformation of Trp277 into glycine hydroperoxide were glycan dependent during incubation for 3 months at 40 degrees C. Our data will show that different glycans not only affect chemical degradation differently but also do lead to different impurity profiles, which can affect chemical degradation. PMID- 26869423 TI - Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying. AB - The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 degrees C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 degrees C to 6.3% at 150 degrees C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins. PMID- 26869422 TI - Biosimilarity Assessments of Model IgG1-Fc Glycoforms Using a Machine Learning Approach. AB - Biosimilarity assessments are performed to decide whether 2 preparations of complex biomolecules can be considered "highly similar." In this work, a machine learning approach is demonstrated as a mathematical tool for such assessments using a variety of analytical data sets. As proof-of-principle, physical stability data sets from 8 samples, 4 well-defined immunoglobulin G1-Fragment crystallizable glycoforms in 2 different formulations, were examined (see More et al., companion article in this issue). The data sets included triplicate measurements from 3 analytical methods across different pH and temperature conditions (2066 data features). Established machine learning techniques were used to determine whether the data sets contain sufficient discriminative power in this application. The support vector machine classifier identified the 8 distinct samples with high accuracy. For these data sets, there exists a minimum threshold in terms of information quality and volume to grant enough discriminative power. Generally, data from multiple analytical techniques, multiple pH conditions, and at least 200 representative features were required to achieve the highest discriminative accuracy. In addition to classification accuracy tests, various methods such as sample space visualization, similarity analysis based on Euclidean distance, and feature ranking by mutual information scores are demonstrated to display their effectiveness as modeling tools for biosimilarity assessments. PMID- 26869424 TI - The Effect of Capsaicin Derivatives on Tight-Junction Integrity and Permeability of Madin-Darby Canine Kidney Cells. AB - Capsaicin is known to interfere with tight junctions (TJs) of epithelial cells and therefore to enhance paracellular permeability of poorly absorbable drugs. However, due to its low water solubility, pungency, and cytotoxicity, its pharmacologic use is limited. In this study, we investigated the effect of capsaicin derivatives of synthetic (e.g., 10-hydroxy-N-(4-hydroxy-3 methoxybenzyl)decanamide, etc.) and natural (olvanil and dihydrocapsaicin) origin on Madin-Darby Canine Kidney-C7 cells. Impedance spectroscopy was used to determine the transepithelial electrical resistance and the capacitance. Permeability assays with fluorescein isothiocyanate-dextran were carried out to evaluate the impact on cell permeability. The results show that lipophilicity could play an important role for the interference with TJ and that the mechanism is independent from the ion channel TRPV-1 and hence on the flux of calcium into the cells. In summary, we synthesized 4 derivatives of capsaicin of lower lipophilicity and compared their properties with other well-known vanilloids. We show that these compounds are able to enhance the permeability of a hydrophilic macromolecule, by opening the TJ for a shorter time than capsaicin. This behavior is dependent on the lipophilicity of the molecule. Understanding of these phenomena may lead to better control of administration of therapeutic molecules. PMID- 26869425 TI - Preclinical Evaluation of an Epidermal Growth Factor Receptor-Targeted Doxorubicin-Peptide Conjugate: Toxicity, Biodistribution, and Efficacy in Mice. AB - Doxorubicin (DOX) is known to induce apoptosis and necrosis in healthy tissue resulting in unwanted toxicities. To improve the ability of DOX to more specifically target tumors and minimize undesirable side effects, conjugation of DOX with epidermal growth factor receptor (EGFR)--binding peptide (DOX-EBP) has been developed to deliver DOX to EGFR-overexpressing neoplastic cells. Here, we investigated whether DOX-EBP was able to reduce toxicity and enhance anticancer efficacy in vivo through receptor-mediated targeted delivery system. Nude mice were treated with DOX or DOX-EBP to estimate general toxicity, normal tissue damage, biodistribution, and antitumor efficacy. In addition, the expression levels of EGFR in tumor tissues and normal organs were investigated by Western blotting, and their mRNA expression was analyzed by reverse transcription PCR. This study demonstrated that DOX-EBP was able to effectively decrease the distribution of DOX in normal tissues without EGFR overexpressing and reduce DOX induced toxicity. On the other hand, the research also confirmed that DOX-EBP was able to preferentially accumulate DOX in EGFR-overexpressing tumor tissues and showed the enhanced anticancer efficacy over free DOX. DOX-EBP could be used for receptor-targeted chemotherapy with less toxicity and greater efficacy of tumor cells overexpressing EGFR. DOX-EBP conjugate is a good therapeutic agent for cancer treatment. PMID- 26869426 TI - Pulmonary Delivery of the Kv1.3-Blocking Peptide HsTX1[R14A] for the Treatment of Autoimmune Diseases. AB - HsTX1[R14A] is a potent and selective Kv1.3 channel blocker peptide with the potential to treat autoimmune diseases. Given the typically poor oral bioavailability of peptides, we evaluated pulmonary administration of HsTX1[R14A] in rats as an alternative route for systemic delivery. Plasma concentrations of HsTX1[R14A] were measured by liquid chromatography coupled with tandem mass spectrometry in rats receiving intratracheal administration of HsTX1[R14A] in solution (1-4 mg/kg) or a mannitol-based powder (1 mg/kg) and compared with plasma concentrations after intravenous administration (2 mg/kg). HsTX1[R14A] stability in rat plasma and lung tissue was also determined. HsTX1[R14A] was more stable in plasma than in lung homogenate, with more than 90% of the HsTX1[R14A] remaining intact after 5 h, compared with 40.5% remaining in lung homogenate. The terminal elimination half-life, total clearance, and volume of distribution of HsTX1[R14A] after intravenous administration were 79.6 +/- 6.5 min, 8.3 +/- 0.6 mL/min/kg, and 949.8 +/- 71.0 mL/kg, respectively (mean +/- SD). After intratracheal administration, HsTX1[R14A] in solution and dry powder was absorbed to a similar degree, with absolute bioavailability values of 39.2 +/- 5.2% and 44.5 +/- 12.5%, respectively. This study demonstrated that pulmonary administration is a promising alternative for systemically delivering HsTX1[R14A] for treating autoimmune diseases. PMID- 26869427 TI - Applicability and Limitations of Cell-Penetrating Peptides in Noncovalent Mucosal Drug or Carrier Delivery Systems. AB - Our recent studies show that cell-penetrating peptides (CPPs) have potential to improve the intestinal absorption of peptide and protein drugs safely and effectively when used in the noncovalent drug--CPP approach. To clarify the applicability and limitations of this strategy, the present study examined the effects of cargo size on the absorption-stimulatory effect of CPPs. Different sizes of hydrophilic macromolecular dextran (4.4, 10, and 70 kDa) and polystyrene based nanoparticles (20, 100, and 200 nm) were chosen as the model cargos in this study. In an in situ rat intestinal absorption study, CPPs (octaarginine, Tat, penetratin, and PenetraMax) increased the intestinal absorption of dextran, and the efficiency varied according to the molecular size of dextran. Among the CPPs, D-penetratin showed an enhancing effect even when coadministered with the largest dextran (70 kDa). By contrast, an in vitro study of Caco-2 cell uptake showed that the ability of CPPs to deliver nanoparticles into epithelial cells was dependent on their particle size and that the relatively poor internalization of 200-nm nanoparticles could be facilitated by coincubation with CPPs. These findings suggest that the intrinsic uptake properties of macromolecules and particulate cargos determine the effectiveness of their intestinal mucosal delivery using the noncovalent CPP method. PMID- 26869428 TI - Reversible Opening of Intercellular Junctions of Intestinal Epithelial and Brain Endothelial Cells With Tight Junction Modulator Peptides. AB - The intercellular junctions restrict the free passage of hydrophilic compounds through the paracellular clefts. Reversible opening of the tight junctions of biological barriers is investigated as one of the ways to increase drug delivery to the systemic circulation or the central nervous system. Six peptides, ADT-6, HAV-6, C-CPE, 7-mer (FDFWITP, PN-78), AT-1002, and PN-159, acting on different integral membrane and linker junctional proteins were tested on Caco-2 intestinal epithelial cell line and a coculture model of the blood-brain barrier. All peptides tested in nontoxic concentrations showed a reversible tight junctions modulating effect and were effective to open the paracellular pathway for the marker molecules fluorescein and albumin. The change in the structure of cell cell junctions was verified by immunostaining for occludin, claudin-4,-5, ZO-1, beta-catenin, and E-cadherin. Expression levels of occludin and claudins were measured in both models. We could demonstrate a selectivity of C-CPE, ADT-6, and HAV-6 peptides for epithelial cells and 7-mer and AT-1002 peptides for brain endothelial cells. PN-159 was the most effective modulator of junctional permeability in both models possibly acting via claudin-1 and -5. Our results indicate that these peptides can be effectively and selectively used as potential pharmaceutical excipients to improve drug delivery across biological barriers. PMID- 26869429 TI - Application of Magnesium Pyrophosphate-Based Sponge-Like Microparticles to Enhance the Delivery Efficiency and Adjuvant Effects of Polyriboinosinic Polyribocytidylic Acid in Immune Cells. AB - The magnesium pyrophosphate particle (MgPP) is a unique and safe carrier that is prepared by simply mixing magnesium chloride and sodium pyrophosphate. In this study, we investigated whether MgPP can be used to deliver nucleic acid-based adjuvants to immune cells. Polyriboinosinic-polyribocytidylic acid (polyI:C), a ligand for toll-like receptor 3, was selected as a model nucleic acid-based adjuvant. PolyI:C-loaded MgPP (polyI:C-MgPP) was prepared by adding polyI:C during the MgPP preparation process. Efficient loading of polyI:C into MgPP was confirmed by measuring the absorbance at 260 nm after disruption of polyI:C-MgPP by ethylenediaminetetraacetic acid. Scanning electron microscopy revealed that both MgPP and polyI:C-MgPP had a unique sponge-like shape with a diameter of approximately 1 MUm. PolyI:C-MgPP was more efficiently taken up by toll-like receptor 3-positive RAW264.7 cells than naked polyI:C, and its uptake stimulated increased tumor necrosis factor-alpha production. When the presentation of ovalbumin (OVA), a model antigen, was evaluated after the addition of OVA along with naked polyI:C or polyI:C-MgPP to mouse dendritic DC2.4 cells, polyI:C-MgPP substantially increased OVA presentation. These results indicate that MgPP is a useful delivery vehicle for polyI:C and that polyI:C-MgPP is an effective immune cell adjuvant. PMID- 26869430 TI - Comparison of Linear and Cyclic His-Ala-Val Peptides in Modulating the Blood Brain Barrier Permeability: Impact on Delivery of Molecules to the Brain. AB - The aim of this study is to evaluate the effect of peptide cyclization on the blood-brain barrier (BBB) modulatory activity and plasma stability of His-Ala-Val peptides, which are derived from the extracellular 1 domain of human E-cadherin. The activities to modulate the intercellular junctions by linear HAV4 (Ac-SHAVAS NH2), cyclic cHAVc1 (Cyclo(1,8)Ac-CSHAVASC-NH2), and cyclic cHAVc3 (Cyclo(1,6)Ac CSHAVC-NH2) were compared in in vitro and in vivo BBB models. Linear HAV4 and cyclic cHAVc1 have the same junction modulatory activities as assessed by in vitro MDCK monolayer model and in situ rat brain perfusion model. In contrast, cyclic cHAVc3 was more effective than linear HAV4 in modulating MDCK cell monolayers and in improving in vivo brain delivery of Gd-DTPA on i.v. administration in Balb/c mice. Cyclic cHAVc3 (t1/2 = 12.95 h) has better plasma stability compared with linear HAV4 (t1/2 = 2.4 h). The duration of the BBB modulation was longer using cHAVc3 (2-4 h) compared with HAV4 (<1 h). Both HAV4 and cHAVc3 peptides also enhanced the in vivo brain delivery of IRdye800cw-PEG (25 kDa) as detected by near IR imaging. The result showed that cyclic cHAVc3 peptide had better activity and plasma stability than linear HAV4 peptide. PMID- 26869431 TI - Methylation, Glucuronidation, and Sulfonation of Daphnetin in Human Hepatic Preparations In Vitro: Metabolic Profiling, Pathway Comparison, and Bioactivity Analysis. AB - Our previous study demonstrated that daphnetin is subject to glucuronidation in vitro. However, daphnetin metabolism is still poorly documented. This study aimed to investigate daphnetin metabolism and its consequent effect on the bioactivity. Metabolic profiles obtained by human liver S9 fractions and human hepatocytes showed that daphnetin was metabolized by glucuronidation, sulfonation, and methylation to form 6 conjugates which were synthesized and identified as 7-O glucuronide, 8-O-glucuronide, 7-O-sulfate and 8-O-sulfate, 8-O-methylate, and 7-O suflo-8-O-methylate. Regioselective 8-O-methylation of daphnetin was investigated using in silico docking calculations, and the results suggested that a close proximity (2.03 A) of 8-OH to the critical residue Lysine 144 might be the responsible mechanism. Compared with glucuronidation and sulfonation pathways, the methylation of daphnetin had a high clearance rate (470 MUL/min/mg) in human liver S9 fractions and contributed to a large amount (37.3%) of the methyl derived metabolites in human hepatocyte. Reaction phenotyping studies showed the major role of SULT1A1, -1A2, and -1A3 in daphnetin sulfonation, and soluble COMT in daphnetin 8-O-methylation. Of the metabolites, only 8-O-methyldaphnetin exhibited an inhibitory activity on lymphocyte proliferation comparable to that of daphnetin. In conclusion, methylation is a crucial pathway for daphnetin clearance and might be involved in pharmacologic actions of daphnetin in humans. PMID- 26869432 TI - The Proteome of Filter-Grown Caco-2 Cells With a Focus on Proteins Involved in Drug Disposition. AB - Caco-2 cells are widely used in studies of intestinal cell physiology and drug transport. Here, the global proteome of filter-grown Caco-2 cells was quantified using the total protein approach and compared with the human colon and jejunum proteomes. In total, 8096 proteins were identified. In-depth analysis of proteins defining enterocyte differentiation-including brush-border hydrolases, integrins, and adherens and tight junctions-gave near-complete coverage of the expected proteins. Three hundred twenty-seven absorption, distribution, metabolism and excretion proteins were identified, including 112 solute carriers and 20 ATP binding cassette transporters. OATP2B1 levels were 16-fold higher in Caco-2 cells than in jejunum. To investigate the impact of this difference on in vitro-in vivo extrapolations, we studied the uptake kinetics of the OATP2B1 substrate pitavastatin in Caco-2 monolayers, and found that the contribution of OATP2B1 was 60%-70% at clinically relevant intestinal concentrations. Pitavastatin kinetics was combined with transporter concentrations to model the contribution of active transport and membrane permeation in the jejunum. The lower OATP2B1 expression in jejunum led to a considerably lower transporter contribution (<5%), suggesting that transmembrane diffusion dominates pitavastatin absorption in vivo. In conclusion, we present the first in-depth quantification of the filter-grown Caco 2 proteome. We also demonstrate the crucial importance of considering transporter expression levels for correct interpretation of drug transport routes across the human intestine. PMID- 26869433 TI - Usefulness of A Model-Based Approach for Estimating In Vitro P-Glycoprotein Inhibition Potency in a Transcellular Transport Assay. AB - In vitro half-maximal inhibitory concentration (IC50) is a key parameter for accurately predicting the potential risk for P-glycoprotein (P-gp)--mediated drug -drug interactions. We aimed to compare the IC50 values estimated by different approaches and determine the usefulness of model-based approaches. Transcellular transport of digoxin across Caco-2 monolayer was investigated using various concentrations of P-gp inhibitors, quinidine, verapamil, and zosuquidar. To calculate IC50 values, 3 traditional parameters were used: apical-to-basal (AtoB) and basal-to-apical (BtoA) clearance (CL) with inhibitors (CLAtoB,i and CLBtoA,i) and the difference between the efflux ratios (ERs) with P-gp inhibitors (ERi) and those under complete P-gp inhibition [ER(-P-gp)]. Furthermore, a new model-based approach was applied that uses the difference between the reciprocals of CLAtoB with P-gp inhibitors (1/CLAtoB,i) and those under complete P-gp inhibition [1/CLAtoB(-P-gp)] as parameters. IC50 values obtained from 2 model-based approaches [ERi - ER(-P-gp) and 1/CLAtoB,i - 1/CLAtoB(-P-gp)] were comparable, whereas 2.6- to 6.6-fold larger IC50 values were estimated from empirical approaches (CLAtoB,i and CLBtoA,i). The reason for such difference in IC50 values is that indicators for model-based approaches, but not empirical approaches, directly reflect the P-gp function. Our new approach [1/CLAtoB,i - 1/CLAtoB(-P gp)] based on only AtoB transcellular transport could substitute for current estimation methods using ER. PMID- 26869434 TI - The Disposition of Oxymatrine in the Vascularly Perfused Rat Intestine-Liver Preparation and Its Metabolism in Rat Liver Microsomes. AB - The study was aimed to investigate the absorption and metabolism of oxymatrine (OMT) which contributed to its poor bioavailability. Determinations of OMT absorption and metabolism in rats were evaluated using techniques of the in situ perfused rat intestine-liver preparation and recirculated intestine preparation. Furthermore, chemical inhibition experiments in rat liver microsomes were used to determine the principal cytochrome P450 (CYP) isoforms involved in OMT metabolism. In the intestine-liver preparation, the steady state liver extraction ratio (0.753 +/- 0.054) of OMT was 33 times higher than that for the intestine (0.023 +/- 0.002). The portal vein mainly consisted of OMT, and was devoid of the metabolite matrine, whereas both OMT and matrine were detected in hepatic vein. With the intestine preparation, the extent of OMT absorption at the end of 120 min of perfusion was 4.79 +/- 0.352%. The first-order rate constant for OMT absorption was 0.05 +/- 0.003 min(-1). The inhibitor of CYP3A2 had strong inhibitory effect on OMT metabolism in a concentration-dependent manner, and value was reduced to 29.73% of control. The 2 perfusion techniques indicated that poor bioavailability of OMT in rats is due mostly to poor absorption and higher hepatic elimination and CYP3A2 appears to contribute to OMT metabolism in rat liver. PMID- 26869435 TI - Quantitative and Mechanistic Assessment of Model Lipophilic Drugs in Micellar Solutions in the Transport Kinetics Across MDR1-MDCK Cell Monolayers. AB - An approach to characterizing P-glycoprotein (Pgp) interaction potential for sparingly water-soluble compounds was developed using bidirectional transport kinetics in MDR1-MDCK cell monolayers. Paclitaxel, solubilized in a dilute polysorbate 80 (PS80) micellar solution, was used as a practical example. Although the passage of paclitaxel across the cell monolayer was initially governed by the thermodynamic activity of the micelle-solubilized drug solution, Pgp inhibition was sustained by the thermodynamic activity (i.e., critical micelle concentration) of the PS80 micellar solution bathing the apical (ap) membrane. The mechanistic understanding of the experimental strategies and treatment of data was supported by a biophysical model expressed in the form of transport events occurring at the ap and basolateral (bl) membranes in series whereas the vectorial directions of the transcellular kinetics were accommodated. The derived equations permitted the stepwise quantitative delineation of the Pgp efflux activity (inhibited and uninhibited by PS80) and the passive permeability coefficient of the ap membrane, the passive permeability at the bl membrane and, finally, the distinct coupling of these with efflux pump activity to identify the rate-determining steps and mechanisms. The Jmax/KM(*) for paclitaxel was in the order of 10(-4) cm/s and the ap- and bl-membrane passive permeability coefficients were asymmetric, with bl-membrane permeability significantly greater than ap. PMID- 26869436 TI - Application of a Human Intestinal Epithelial Cell Monolayer to the Prediction of Oral Drug Absorption in Humans as a Superior Alternative to the Caco-2 Cell Monolayer. AB - A human small intestinal epithelial cell (HIEC) monolayer was recently established in our laboratories as a novel system to evaluate the Papp (apparent permeability coefficient) of compounds during their absorption in humans. An effusion-based analysis using polyethylene glycol oligomers with molecular weights ranging from 194-898 indicated that HIEC and Caco-2 cell monolayers both had paracellular pores with 2 distinct radiuses (~ 5 and 9-14 A), whereas the porosity of large pores was 11-fold higher in the HIEC monolayer (44 * 10(-8)) than in the Caco-2 cells (4 * 10(-8)). A comparison between the fraction-absorbed (Fa) values observed in humans and those predicted from Papp values in both monolayers indicated that the HIEC monolayer had markedly higher precision to predict Fa values with root mean square error of 9.40 than the Caco-2 cells (root mean square error = 16.90) for 10 paracellularly absorbed compounds. Furthermore, the accuracy of the HIEC monolayer to classify the absorption of 23 test drugs with diverse absorption properties, including different pathways in the presence or absence of susceptibility to efflux transporters, was higher than that of the Caco-2 cell monolayer. In conclusion, the HIEC monolayer exhibited advantages over Caco-2 cells in the ranking and prediction of absorption of compounds in humans. PMID- 26869438 TI - Genetically Modified Caco-2 Cells With Improved Cytochrome P450 Metabolic Capacity. AB - The human intestinal Caco-2 cell line has been extensively used as a model of small intestinal absorption but it lacks expression and function of cytochrome P450 enzymes, particularly CYP3A4 and CYP2C9, which are normally expressed in the intestinal epithelium. In order to increase the expression and activity of CYP isozymes in these cells, we created 2 novel Caco-2 sublines expressing chimeric constitutive androstane or pregnane X receptors and characterized these cells for their metabolic and absorption properties. In spite of elevated mRNA expression of transporters and differentiation markers, the permeation properties of the modified cell lines did not significantly differ from those of the wild-type cells. In contrast, the metabolic activity was increased beyond the currently used models. Specifically, CYP3A4 activity was increased up to 20-fold as compared to vitamin D treated wild-type Caco-2 cells. PMID- 26869437 TI - Carrier-Mediated Prodrug Uptake to Improve the Oral Bioavailability of Polar Drugs: An Application to an Oseltamivir Analogue. AB - The goal of this study was to improve the intestinal mucosal cell membrane permeability of the poorly absorbed guanidino analogue of a neuraminidase inhibitor, oseltamivir carboxylate (GOC) using a carrier-mediated strategy. Valyl amino acid prodrug of GOC with isopropyl-methylene-dioxy linker (GOC-ISP-Val) was evaluated as the potential substrate for intestinal oligopeptide transporter, hPEPT1 in Xenopus laevis oocytes heterologously expressing hPEPT1, and an intestinal mouse perfusion system. The diastereomers of GOC-ISP-Val were assessed for chemical and metabolic stability. Permeability of GOC-ISP-Val was determined in Caco-2 cells and mice. Diastereomer 2 was about 2 times more stable than diastereomer 1 in simulated intestinal fluid and rapidly hydrolyzed to the parent drug in cell homogenates. The prodrug had a 9 times-enhanced apparent permeability (P(app)) in Caco-2 cells compared with the parent drug. Both diastereomer exhibited high effective permeability (P(eff)) in mice, 6.32 +/- 3.12 and 5.20 +/- 2.81 * 10(-5) cm/s for diastereomer 1 and 2, respectively. GOC ISP-Val was found to be a substrate of hPEPT1. Overall, this study indicates that the prodrug, GOC-ISP-Val, seems to be a promising oral anti-influenza agent that has sufficient stability at physiologically relevant pHs before absorption, significantly improved permeability via hPEPT1 and potentially rapid activation in the intestinal cells. PMID- 26869440 TI - Insights From an Integrated Physiologically Based Pharmacokinetic Model for Brain Penetration. AB - Central-nervous-system, physiologically based pharmacokinetic (PBPK) models predict exposure profiles in the brain, that is, the rate and extent of distribution. The current work develops one such model and presents improved methods for determining key input parameters. A simple linear regression statistical model estimates the passive permeability at the blood-brain barrier from brain uptake index data and descriptors, and a novel analysis extracts the relative active transport parameter from in vitro assays taking into consideration both paracellular transport and unstirred water layers. The integrated PBPK model captures the concentration profiles of both rate-restricted and effluxed compounds with high passive permeability. In many cases, compounds distribute rapidly into the brain and are, therefore, not rate limited. The PBPK model is then simplified to a straightforward equation to describe brain-to plasma ratios at steady state. The equation can estimate brain penetration either from in vitro efflux data or from in vivo results from another species and, therefore, is a valuable tool in the discovery setting. PMID- 26869439 TI - Co-culture of Hepatocytes and Kupffer Cells as an In Vitro Model of Inflammation and Drug-Induced Hepatotoxicity. AB - Immune-mediated drug-induced hepatotoxicity is often unrecognized as a potential mode of action due to the lack of appropriate in vitro models. We have established an in vitro rat donor-matched hepatocyte and Kupffer cell co-culture (HKCC) model to study immune-related responses to drug exposure. Optimal cell culture conditions were identified for the maintenance of co-cultures based on cell longevity, monolayer integrity, and cytokine response after lipopolysaccharide (LPS) exposure. Hepatocyte monocultures and HKCCs were then used to test a subset of compounds associated with hepatotoxic effects with or without LPS. Cytokine levels and metabolic activity (cytochrome P450 3A [Cyp3A]) were measured after a 48-h exposure to monitor endotoxin-induced changes in acute phase and functional end points. LPS-activated HKCCs, but not hepatocyte monocultures, treated with trovafloxacin or acetaminophen, compounds associated with immune-mediated hepatotoxicity, showed LPS-dependent decreases in interleukin-6 production with concomitant increases in Cyp3A activity. Differential endotoxin- and model-dependent alterations were observed in cytokine profiles and Cyp3A activity levels that corresponded to specific compounds. These results indicate the utility of the HKCC model system to discern compound specific effects that may lead to enhanced or mitigate hepatocellular injury due to innate or adaptive immune responses. PMID- 26869443 TI - Correlating Hemodynamic Changes and Occlusion Time after Flow Diverter Treatment of Bilateral Large Internal Carotid Artery Aneurysms. PMID- 26869442 TI - Complete Knockout of Endogenous Mdr1 (Abcb1) in MDCK Cells by CRISPR-Cas9. AB - Madin-Darby canine kidney II cells transfected with one or several transport proteins are commonly used models to study drug transport. In these cells, however, endogenous transporters such as canine Mdr1/P-glycoprotein (Abcb1) complicate the interpretation of transport studies. The aim of this investigation was to establish a Madin-Darby canine kidney II cell line using CRISPR-Cas9 gene editing technology to knock out endogenous canine Mdr1 (cMdr1) expression. CRISPR Cas9-mediated Abcb1 homozygous disruption occurred at frequencies of around 20% and resulted in several genotypes. We selected 1 clonal cell line, cMdr1 KO Cl2, for further examination. Consistent with an on-target effect of CRISPR-Cas9 in specific regions of the endogenous canine Abcb1 gene, we obtained a cell clone with Abcb1 gene alterations and without any cMdr1 expression, as confirmed by genome sequencing and quantitative protein analysis. Functional studies of these cells, using digoxin and other prototypic MDR1 substrates, showed close to identical transport in the apical-to-basolateral and basolateral-to-apical directions, resulting in efflux ratios indistinguishable from unity. PMID- 26869441 TI - Quantitation of Polymyxin-Lipopolysaccharide Interactions Using an Image-Based Fluorescent Probe. AB - The frequency of polymyxin-resistant pathogenic Gram-negative bacteria appearing in the clinic is increasing, and the consequences are largely mediated by modification of lipopolysaccharide (LPS) in the outer membrane. As polymyxins exert their antibacterial effect by binding to LPS, understanding their mode of binding will prove highly valuable for new antibiotic discovery. In this study, we assess the potential of MIPS-9451, a fluorescent polymyxin analogue designed for imaging studies, as a fluorescent reporter molecule, titrating it against 17 different Gram-negative species and/or strains of LPS. MIPS-9451 bound to the various species and/or strains of LPS with a dissociation constant ranging between 0.14 +/- 0.01 MUM (Escherichia coli) and 0.90 +/- 0.42 MUM (Porphyromonas gingivalis; mean +/- standard error). Furthermore, we assessed the applicability of MIPS-9451 to rank affinities of polymyxin B to different LPS species in a displacement assay which yielded inhibition constants of 6.2 MUM +/- 33%, 7.2 MUM +/- 30%, and 0.95 MUM +/- 13% for Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella enterica, respectively (mean +/- coefficient of variation). The results from this study are concordant with those observed with similarly structured polymyxin probes, confirming the potential of MIPS-9451 for quantitation of polymyxin-LPS affinities in discovery programs of novel polymyxin antibiotics. PMID- 26869444 TI - Anatomic and Quantitative Temporal Bone CT for Preoperative Assessment of Branchio-Oto-Renal Syndrome. AB - We describe the temporal bone computed tomography (CT) findings of an unusual case of branchio-oto-renal syndrome with ectopic ossicles that are partially located in the middle cranial fossa. We also describe quantitative temporal bone CT assessment pertaining to cochlear implantation in the setting of anomalous cochlear anatomy associated with this syndrome. PMID- 26869445 TI - Application of a Dedicated Surface Coil in Dental MRI Provides Superior Image Quality in Comparison with a Standard Coil. AB - PURPOSE: Purpose of our research was the evaluation of a dedicated dental surface coil in comparison with a standard head and neck coil for the improvement of dental magnetic resonance imaging (MRI). MATERIALS AND METHODS: Axial T1-weighted spin echo MRI was performed by using a newly developed dental coil for MRI and a standard head and neck coil on five volunteers. In addition, MRI was implemented with dental coil on five patients. Using the Wilcoxon test, we compared the volunteers' signal-to-noise ratio (SNR) of a variety of anatomical structures (e.g., hard tooth tissue, pulp tissue, bone, muscle tissue). Also subjective evaluation of image quality was performed on both volunteers and patients. RESULTS: Compared with the head and neck coil, the mean SNR was 3.5-fold higher on an average with the dental coil (range: from 2.7 [masseter muscle] to 4.6 [pulp tissue]). That difference was statistically significant for all evaluated structures. The higher SNR also resulted in a superior image quality as determined by subjective evaluation. CONCLUSION: Dental MRI benefits profoundly from using a dedicated dental coil. PMID- 26869446 TI - Linoleic acid permeabilizes gastric epithelial cells by increasing connexin 43 levels in the cell membrane via a GPR40- and Akt-dependent mechanism. AB - Linoleic acid (LA) is known to activate G-protein coupled receptors and connexin hemichannels (Cx HCs) but possible interlinks between these two responses remain unexplored. Here, we evaluated the mechanism of action of LA on the membrane permeability mediated by Cx HCs in MKN28 cells. These cells were found to express connexins, GPR40, GPR120, and CD36 receptors. The Cx HC activity of these cells increased after 5 min of treatment with LA or GW9508, an agonist of GPR40/GPR120; or exposure to extracellular divalent cation-free solution (DCFS), known to increase the open probability of Cx HCs, yields an immediate increase in Cx HC activity of similar intensity and additive with LA-induced change. Treatment with a CD36 blocker or transfection with siRNA-GPR120 maintains the LA-induced Cx HC activity. However, cells transfected with siRNA-GPR40 did not show LA-induced Cx HC activity but activity was increased upon exposure to DCFS, confirming the presence of activatable Cx HCs in the cell membrane. Treatment with AKTi (Akt inhibitor) abrogated the LA-induced Cx HC activity. In HeLa cells transfected with Cx43 (HeLa-Cx43), LA induced phosphorylation of surface Cx43 at serine 373 (S373), site for Akt phosphorylation. HeLa-Cx43 but not HeLa-Cx43 cells with a S373A mutation showed a LA-induced Cx HC activity directly related to an increase in cell surface Cx43 levels. Thus, the increase in membrane permeability induced by LA is mediated by an intracellular signaling pathway activated by GPR40 that leads to an increase in membrane levels of Cx43 phosphorylated at serine 373 via Akt. PMID- 26869448 TI - Crystal structure of the Saccharomyces cerevisiae monoglyceride lipase Yju3p. AB - Monoglyceride lipases (MGLs) are a group of alpha/beta-hydrolases that catalyze the hydrolysis of monoglycerides (MGs) into free fatty acids and glycerol. This reaction serves different physiological functions, namely in the last step of phospholipid and triglyceride degradation, in mammalian endocannabinoid and arachidonic acid metabolism, and in detoxification processes in microbes. Previous crystal structures of MGLs from humans and bacteria revealed conformational plasticity in the cap region of this protein and gave insight into substrate binding. In this study, we present the structure of a MGL from Saccharomyces cerevisiae called Yju3p in its free form and in complex with a covalently bound substrate analog mimicking the tetrahedral intermediate of MG hydrolysis. These structures reveal a high conservation of the overall shape of the MGL cap region and also provide evidence for conformational changes in the cap of Yju3p. The complex structure reveals that, despite the high structural similarity, Yju3p seems to have an additional opening to the substrate binding pocket at a different position compared to human and bacterial MGL. Substrate specificities towards MGs with saturated and unsaturated alkyl chains of different lengths were tested and revealed highest activity towards MG containing a C18:1 fatty acid. PMID- 26869449 TI - Lipid accumulation stimulates the cap-independent translation of SREBP-1a mRNA by promoting hnRNP A1 binding to its 5'-UTR in a cellular model of hepatic steatosis. AB - Non-alcoholic fatty liver disease (NAFLD) is a chronic disease characterized by accumulation of lipid droplets in hepatocytes. Enhanced release of non-esterified fatty acids from adipose tissue accounts for a remarkable fraction of accumulated lipids. However, the de novo lipogenesis (DNL) is also implicated in the etiology of the NAFLD. Sterol Regulatory Element-Binding Protein-1 (SREBP-1) is a transcription factor modulating the expression of several lipogenic enzymes. In the present study, in order to investigate the effect of lipid droplet accumulation on DNL, we used a cellular model of steatosis represented by HepG2 cells cultured in a medium supplemented with free oleic and palmitic fatty acids (FFAs). We report that FFA supplementation induces the expression of genes coding for enzymes involved in the DNL as well as for the transcription factor SREBP-1a. The SREBP-1a mRNA translation, dependent on an internal ribosome entry site (IRES), and the SREBP-1a proteolytic cleavage are activated by FFAs. Furthermore, FFA treatment enhances the expression and the nucleus-cytosolic shuttling of hnRNP A1, a trans-activating factor of SREBP-1a IRES. The binding of hnRNP A1 to the SREBP-1a IRES is also increased upon FFA supplementation. The relocation of hnRNP A1 and the consequent increase of SREBP-1a translation are dependent on the p38 MAPK signal pathway, which is activated by FFAs. By RNA interference approach, we demonstrate that hnRNP A1 is implicated in the FFA-induced expression of SREBP-1a and of its target genes as well as in the lipid accumulation in cells. PMID- 26869447 TI - miRNAs and High-Density Lipoprotein metabolism. AB - Altered lipoprotein metabolism plays a key role during atherogenesis. For over 50years, epidemiological data have fueled the proposal that HDL-cholesterol (HDL c) in circulation is inversely correlated to cardiovascular risk. However, the atheroprotective role of HDL is currently the focus of much debate and remains an active field of research. The emerging picture from research in the past decade suggests that HDL function, rather than HDL-c content, is important in disease. Recent developments demonstrate that miRNAs play an important role in fine-tuning the expression of key genes involved in HDL biogenesis, lipidation, and clearance, as well as in determining the amounts of HDL-c in circulation. Thus, it has been proposed that miRNAs that affect HDL metabolism might be exploited therapeutically in patients. Whether HDL-based therapies, alone or in combination with LDL-based treatments (e.g. statins), provide superior outcomes in patients has been recently questioned by human genetics studies and clinical trials. The switch in focus from "HDL-cholesterol" to "HDL function" opens a new paradigm to understand the physiology and therapeutic potential of HDL, and to find novel modulators of cardiovascular risk. In this review we summarize the current knowledge on the regulation of HDL metabolism and function by miRNAs. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez. PMID- 26869450 TI - How did nature engineer the highest surface lipid accumulation among plants? Exceptional expression of acyl-lipid-associated genes for the assembly of extracellular triacylglycerol by Bayberry (Myrica pensylvanica) fruits. AB - Bayberry (Myrica pensylvanica) fruits are covered with a remarkably thick layer of crystalline wax consisting of triacylglycerol (TAG) and diacylglycerol (DAG) esterified exclusively with saturated fatty acids. As the only plant known to accumulate soluble glycerolipids as a major component of surface waxes, Bayberry represents a novel system to investigate neutral lipid biosynthesis and lipid secretion by vegetative plant cells. The assembly of Bayberry wax is distinct from conventional TAG and other surface waxes, and instead proceeds through a pathway related to cutin synthesis (Simpson and Ohlrogge, 2016). In this study, microscopic examination revealed that the fruit tissue that produces and secretes wax (Bayberry knobs) is fully developed before wax accumulates and that wax is secreted to the surface without cell disruption. Comparison of transcript expression to genetically related tissues (Bayberry leaves, M. rubra fruits), cutin-rich tomato and cherry fruit epidermis, and to oil-rich mesocarp and seeds, revealed exceptionally high expression of 13 transcripts for acyl-lipid metabolism together with down-regulation of fatty acid oxidases and desaturases. The predicted protein sequences of the most highly expressed lipid-related enzyme encoding transcripts in Bayberry knobs are 100% identical to the sequences from Bayberry leaves, which do not produce surface DAG or TAG. Together, these results indicate that TAG biosynthesis and secretion in Bayberry is achieved by both up and down-regulation of a small subset of genes related to the biosynthesis of cutin and saturated fatty acids, and also implies that modifications in gene expression, rather than evolution of new gene functions, was the major mechanism by which Bayberry evolved its specialized lipid metabolism. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID- 26869451 TI - Seasonal variability of faecal indicator bacteria numbers and die-off rates in the Red River basin, North Viet Nam. AB - The Red River is the second largest river in Viet Nam and constitutes the main water source for a large percentage of the population of North Viet Nam. Here we present the results of an annual survey of Escherichia coli (EC) and Total Coliforms (TC) in the Red River basin, North Viet Nam. The objective of this work was to obtain information on faecal indicator bacteria (FIB) numbers over an annual cycle and, secondly, to determine the die-off rates of these bacterial indicators. Monthly observations at 10 stations from July 2013-June 2014 showed that TC and EC reached as high as 39100 cfu (colony forming units) 100 ml(-1) and 15300 colonies 100 ml(-1), respectively. We observed a significant seasonal difference for TC (p < 0.05) with numbers being higher during the wet season. In contrast, no significant seasonal difference was found for EC. The FIB die-off rates ranged from 0.01 d(-1) to a maximum of 1.13 d(-1) for EC and from 0.17 d( 1) to 1.33 d(-1) for TC. Die-off rates were significantly higher for free bacteria than for total (free + particle attached) bacteria, suggesting that particle attachment provided a certain level of protection to FIB in this system. PMID- 26869452 TI - Description of Leucobacter holotrichiae sp. nov., isolated from the gut of Holotrichia oblita larvae. AB - A Gram-stain-positive bacterium, designated T14T, was isolated from the gut of Holotrichia oblita larvae and was subjected to a taxonomic study. The isolate was rod-shaped, aerobic, non-motile, non-spore-forming and yellow-pigmented. Phylogenetic analysis based on 16S rRNA gene sequence comparison indicated that the isolate is related to the genus Leucobacter. Its closest neighbours were the type strains 'Leucobacter kyeonggiensis' F3-P9 (96.8% 16S rRNA gene sequence similarity), Leucobacter celer NAL101T (96.2%) and Leucobacter chironomi DSM 19883T (95.5%). The DNA G+C content of strain T14T was 69.3 mol%, and DNA-DNA hybridization values with closely related strains were <32%. The predominant cellular fatty acids were anteiso-C15:0 (49.3%), iso-C16:0 (16.4%) and anteiso C17:0 (16.8%). The major polar lipids were aminolipid, diphosphatidylglycerol, phosphatidylglycerol, phospholipid, phosphoglycolipid and unidentified glycolipids. The predominant respiratory quinone was MK-11. Based on these phylogenetic and phenotypic results, strain T14T can be clearly distinguished from all of the recognized species of the genus Leucobacter and is considered to represent a novel species of the genus Leucobacter. The name Leucobacter holotrichiae sp. nov. is proposed, with the type strain T14T (=DSM 28968T=JCM 30245T). PMID- 26869454 TI - Two in one: switchable ion conductivity and white light emission integrated in an iodoplumbate-based twin chain hybrid crystal. AB - An iodoplumbate-based hybrid, [C7-Apy][PbI3] (1), where C7-Apy(+) = 1-heptyl-4 aminopyridinium, was prepared using a simple solution process. Three sequential phase transitions occur in the range of 402-443 K. In both the lowest and highest temperature phases, hybrid crystal 1 is composed of discrete [Pb2I6]infinity twin chains surrounded by C7-Apy(+) cations. The connectivity between PbI6 octahedra within a [Pb2I6]infinity twin chain and the arrangement of cations are quite difference between the lowest and highest temperature phases. Hybrid crystal 1 shows switchable ion conductivity due to the structural phase transition and white light emission attributed to the broad band semiconductor emission of the twin chain. The former functionality has potential application in ion conductor devices; the single-phase white light emitter is a useful material in low-cost, easily-made, high-efficiency white light-emitting diodes. PMID- 26869453 TI - Supra-nutritional levels of alpha-tocopherol maintain the oxidative stability of n-3 long-chain fatty acid enriched subcutaneous fat and frozen loin, but not of dry fermented sausage. AB - BACKGROUND: Meat products enriched with n-3 fatty acids are more prone to oxidation. The aim was to investigate whether supra-nutritional levels of alpha tocopherol can enhance the colour and lipid oxidative stability of n-3 fatty acids enriched dry fermented sausages, frozen loins and subcutaneous fat. Pigs were fed a diet supplemented with 18 g kg(-1) fish oil and 50, 150 or 300 mg kg( 1) alpha-tocopheryl acetate. The control group received 12 g kg(-1) soy oil and 150 mg kg(-1) alpha-tocopheryl acetate. RESULTS: alpha-Tocopherol levels of the frozen loin, dry fermented sausage and subcutaneous fat were elevated as a result of the dietary alpha-tocopherol supplementation. Lipid oxidation occurred to the same extend in the n-3 fatty acid enriched frozen loins when compared to the control group. In the subcutaneous fat enriched with n-3 fatty acids reduced lipid oxidation was found when comparing 50 mg kg(-1) versus 150 and 300 mg kg( 1) . However, in the dry fermented sausages no such effect was observed and higher TBARS values were found in the n-3 fatty acid enriched sausages compared to the control group. Colour parameters of the loin and subcutaneous fat were not affected, whereas some significant differences in the dry fermented sausages were found. The colour stability of the frozen loins was not affected by the dietary treatments. CONCLUSION: Supra-nutritional levels of alpha-tocopherol maintain the oxidative stability of n-3 fatty acid enriched frozen loins and subcutaneous fat, but not of dry fermented sausages. (c) 2016 Society of Chemical Industry. PMID- 26869455 TI - Prospective association of sugar-sweetened and artificially sweetened beverage intake with risk of hypertension. AB - BACKGROUND: Several observational studies have suggested that high consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) is associated with increased blood pressure, but this relationship has not been investigated comprehensively. AIMS: To quantitatively examine the association between sugar-sweetened and artificially sweetened beverage intake and risk of hypertension. METHODS: We performed a systematic review and meta-analysis of eligible prospective cohort studies, identified by searching PubMed, Embase and Web of Science databases up to May 2015. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least-squares trend estimation was used to assess dose-response relationships. RESULTS: Six studies (246,822 subjects and 80,628 incident cases of hypertension) were identified for the meta-analysis of SSBs and hypertension. The pooled RR of hypertension in the highest category of SSB consumption (>=1 serving/day, mean) compared with the lowest category of SSB (<0.6 serving/month, mean) was 1.12 (95% CI: 1.07, 1.17). In a dose-response analysis, a 1 serving/day increase in SSB intake was associated with an 8% increased risk of hypertension (RR: 1.08, 95% CI: 1.06, 1.11). Four studies (227,254 subjects and 78,177 incident cases of hypertension) were included in the meta-analysis of ASBs and hypertension. The pooled RRs were 1.14 (95% CI: 1.10, 1.18) for highest versus lowest analysis and 1.09 (95% CI: 1.06, 1.11) for every additional 1 serving/day increase in ASB consumption. The positive association did not vary significantly by sex, duration of follow-up or adjustment for body mass index. CONCLUSIONS: Our findings indicate that high SSB and ASB consumption is associated with an increased risk of hypertension. PMID- 26869456 TI - Anthraquinone Glycoside Aloin Induces Osteogenic Initiation of MC3T3-E1 Cells: Involvement of MAPK Mediated Wnt and Bmp Signaling. AB - Osteoporosis is a bone pathology leading to increased fracture risk and challenging the quality of life. The aim of this study was to evaluate the effect of an anthraquinone glycoside, aloin, on osteogenic induction of MC3T3-E1 cells. Aloin increased alkaline phosphatase (ALP) activity, an early differentiation marker of osteoblasts. Aloin also increased the ALP activity in adult human adipose-derived stem cells (hADSC), indicating that the action of aloin was not cell-type specific.Alizarin red S staining revealed a signifiant amount of calcium deposition in cells treated with aloin. Aloin enhanced the expression of osteoblast differentiation genes, Bmp-2, Runx2 and collagen 1a, in a dose dependent manner. Western blot analysis revealed that noggin and inhibitors of p38 MAPK and SAPK/JNK signals attenuated aloin-promoted expressions of Bmp-2 and Runx2 proteins. siRNA mediated blocking of Wnt-5a signaling pathway also annulled the influenceof aloin, indicating Wnt-5a dependent activity. Inhibition of the different signal pathways abrogated the influenceof aloin on ALP activity, confirmingthat aloin induced MC3T3-E1 cells into osteoblasts through MAPK mediated Wnt and Bmp signaling pathway. PMID- 26869457 TI - Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation. AB - Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material. PMID- 26869458 TI - Transplant related ocular surface disorders: Advanced techniques for ocular surface rehabilitation after ocular complications secondary to hematopoietic stem cell transplantation. AB - HSCT has been linked to the development of an assortment of ocular surface complications with the potential to lead to permanent visual impairment if left untreated or if not treated early in the course of disease. Strategies for therapy include maintenance of lubrication and tear preservation, prevention of evaporation, decreasing inflammation, and providing epithelial support. The ultimate aim of treatment is to prevent permanent ocular sequelae through prompt ophthalmology consultation and the use of advanced techniques for ocular surface rehabilitation. We describe several rehabilitation options of ocular surface complications occurring secondarily during the post-HSCT course. PMID- 26869460 TI - Long term impact of one daily unit of physical exercise at school on cardiovascular risk factors in school children. AB - BACKGROUND: Obesity and physical inactivity in children correlate with the presence of cardiovascular risk factors. The aim of this prospective, randomised, interventional study was to examine the long term impact of additional physical exercise lessons at school on fitness and cardiovascular risk factors. METHODS: We randomly assigned 366 5th and 6th grade students class-wise into an intervention group that participated in one-daily physical exercise unit at school and a control group, participating in conventional school sports twice a week. The intervention duration was 4 years. At baseline and yearly follow-up, anthropometric measurements, body coordination tests, spiroergometry, questionnaires and blood samples were performed. RESULTS: A total of 236 children qualified for analysis of the intervention effect after 4 years. At the beginning students of the intervention and control groups had similar values for fitness assessed by peak oxygen uptake. Peak oxygen uptake was significantly better in the intervention group at first and second follow-up. After 4 years we found no difference in fitness any longer. Students in the intervention group were more likely to have healthy body mass index percentiles in comparison to the control group (within 10th to 90th percentile: intervention 86.4%, control 78.2%, P = 0.13). CONCLUSION: Over a period of 1-2 years, additional physical exercise lessons at school resulted in an improvement of fitness. However, long-term follow-up failed to demonstrate ongoing improvement of performance in the intervention compared with the control group. Nevertheless, the intervention group had lower rates of body mass index above the 90th percentile throughout the entire follow-up. Therefore more physical exercise units at school seem justified. PMID- 26869459 TI - The impact of multiple single day blood pressure readings on cardiovascular risk estimation: The Atherosclerosis Risk in Communities study. AB - AIMS: The aim of this study was to determine the magnitude of change in estimated cardiovascular disease risk when multiple same day blood pressure measurements are used in estimating coronary heart disease, heart failure and stroke risks. METHODS AND RESULTS: Black and White participants, N = 11,129, enrolled in the Atherosclerosis Risk in Communities study (mean age 53.9 +/- 5.7 (SD) years) were included. Each participant had three sitting, five supine, and six standing blood pressure measures during one day. Main outcome measures were changes in estimated coronary heart disease, heart failure and stroke risk when using the different blood pressure measures. Mean sitting, standing and supine systolic blood pressure values of the study population were 120.8 +/- 18.6, 124.9 +/- 20 and 124.7 +/- 19.6 mmHg, respectively. The substitution of the second sitting systolic blood pressure with the third sitting systolic blood pressure (taken ~5 min later) in two separate coronary heart disease risk models reclassified 3.3% to 5.1% of study participants. Similar substitutions for heart failure and stroke risk prediction models led to reclassification of 1.9% and 2.7% of participants respectively. When mean sitting systolic blood pressure was replaced with mean standing systolic blood pressure 5.4% to 11.6% of the participants were reclassified. Maximum upward and downward change in an individual's estimated risk was 31% and 26% respectively. CONCLUSIONS: Estimated risks of coronary heart disease, heart failure, and stroke for an individual can change significantly within a day due to changes in systolic blood pressure. Given recommendations to use estimated risk for therapeutic decisions, our study has implications for the use of a single systolic blood pressure in cardiovascular risk estimation. PMID- 26869461 TI - Age-stratified trends in 20 years of stress incontinence surgery in Australia. AB - BACKGROUND: Stress urinary incontinence (SUI) is a common, debilitating condition in Australian women. Since its introduction in 1998-1999, the less invasive mid urethral sling (MUS) procedure has become the new standard for surgical correction of SUI and overall numbers of continence procedures increased. Trends since 2009 have not been analysed. AIMS: To identify patterns in the surgical treatment of women with SUI in Australia from January 1994 to December 2014 stratified by age. MATERIALS AND METHODS: Gender- and age-specific data from Medicare Australia between January 1994 and December 2014 were extracted and the patterns of SUI surgery analysed for the 20-year period. Data on gynaecologists and urologists performing MUS and colposuspension were collected from Department of Human Services. RESULTS: Following the introduction of MUS, total SUI operations increased with the peak in 2002, a plateau between 2006 and 2011, and a new decline from 2012 onwards. There has been a sustained 51.7% increase in total SUI operations in 75- to 84-year-old women, and a 105.2% increase in women aged over 84. However, SUI operations in 45- to 64-year-olds decreased below pre MUS baseline in 2014. CONCLUSIONS: Mid-urethral sling has become the standard SUI procedure being performed in Australia since its introduction in 1999. SUI operations have increased each year for patients aged over 65, with the greatest increase seen in patients aged over 84 - indicating expanded eligibility for SUI surgery in older women. However, since 2010, there has been a fall in SUI operations to below the pre-MUS baseline. PMID- 26869462 TI - Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients. AB - Angiogenesis has been postulated to be critical for the pathogenesis of multiple myeloma, a neoplastic disease characterized by abnormal proliferation of malignant plasma cells in the bone marrow (BM). Cleavage of the N- and C-terminal regions of circulating chromogranin A (CgA, CHGA), classically an antiangiogenic protein, can activate latent antiangiogenic and proangiogenic sites, respectively. In this study, we investigated the distribution of CgA-derived polypeptides in multiple myeloma patients and the subsequent implications for disease progression. We show that the ratio of pro/antiangiogenic forms of CgA is altered in multiple myeloma patients compared with healthy subjects and that this ratio is higher in BM plasma compared with peripheral plasma, suggesting enhanced local cleavage of the CgA C-terminal region. Enhanced cleavage correlated with increased VEGF and FGF2 BM plasma levels and BM microvascular density. Using the Vk*MYC mouse model of multiple myeloma, we further demonstrate that exogenously administered CgA was cleaved in favor of the proangiogenic form and was associated with increased microvessel density. Mechanistic studies revealed that multiple myeloma and proliferating endothelial cells can promote CgA C-terminal cleavage by activating the plasminogen activator/plasmin system. Moreover, cleaved and full-length forms could also counter balance the pro/antiangiogenic activity of each other in in vitro angiogenesis assays. These findings suggest that the CgA-angiogenic switch is activated in the BM of multiple myeloma patients and prompt further investigation of this CgA imbalance as a prognostic or therapeutic target. Cancer Res; 76(7); 1781-91. (c)2016 AACR. PMID- 26869463 TI - "Bringing Taxonomy to the Service of Genetics": Edgar Anderson and Introgressive Hybridization. AB - In introgressive hybridization (the repeated backcrossing of hybrids with parental populations), Edgar Anderson found a source for variation upon which natural selection could work. In his 1953 review article "Introgressive Hybridization," he asserted that he was "bringing taxonomy to the service of genetics" whereas distinguished colleagues such as Theodosius Dobzhansky and Ernst Mayr did the precise opposite. His work as a geneticist particularly focused on linkage and recombination and was enriched by collaborations with Missouri Botanical Garden colleagues interested in taxonomy as well as with cytologists C.D. Darlington and Karl Sax. As the culmination of a biosystemtatic research program, Anderson's views challenged the mainstream of the Evolutionary Synthesis. PMID- 26869464 TI - Remembering Our Forebears: Albert Jan Kluyver and the Unity of Life. AB - The Dutch microbiologist/biochemist Albert Jan Kluyver (1888-1956) was an early proponent of the idea of biochemical unity, and how that concept might be demonstrated through the careful study of microbial life. The fundamental relatedness of living systems is an obvious correlate of the theory of evolution, and modern attempts to construct phylogenetic schemes support this relatedness through comparison of genomes. The approach of Kluyver and his scientific descendants predated the tools of modern molecular biology by decades. Kluyver himself is poorly recognized today, yet his influence at the time was profound. Through lens of today however, it has been argued that the focus by Kluyver and others to create taxonomic and phylogenetic schemes using morphology and biochemistry distorted and hindered progress of the discipline of microbiology, because of a perception that the older approaches focused too much on a reductionist worldview. This essay argues that in contrast the careful characterization of fundamental microbial metabolism and physiology by Kluyver made many of the advances of the latter part of the twentieth century possible, by offering a framework which in many respects anticipated our current view of phylogeny, and by directly and indirectly training a generation of scientists who became leaders in the explosive growth of biotechnology. PMID- 26869465 TI - Imaging Signs in Spontaneous Intracranial Hypotension: Prevalence and Relationship to CSF Pressure. AB - BACKGROUND AND PURPOSE: Patients with spontaneous intracranial hypotension often exhibit low CSF pressure and changes on brain MR imaging and/or evidence of CSF leak on myelography. We investigated whether individual imaging signs of spontaneous intracranial hypotension correlate with measured CSF pressure and how frequently these 2 markers of spontaneous intracranial hypotension were concordant. MATERIALS AND METHODS: We performed a retrospective, cross-sectional study of 99 subjects with spontaneous intracranial hypotension. Prevalence of brain and myelographic imaging signs of spontaneous intracranial hypotension was recorded. CSF pressure among subjects with or without individual imaging signs was compared by using a 2-tailed t test and ANOVA. Concordance between low CSF pressure (<=6 cm H2O) and imaging was defined as the presence of the sign in a subject with low CSF pressure or absence of the sign when pressure was not low. RESULTS: Dural enhancement, brain sagging, and venous distension sign were present in 83%, 61%, and 75% of subjects, respectively, and myelographic evidence of CSF leak was seen in 55%. Marginal correlations between CSF pressure and brain sagging (P = .046) and the venous distension sign (P = .047) were found. Dural enhancement and myelographic evidence of leak were not significantly correlated with CSF pressure. Rates of concordance between imaging signs and low CSF pressure were generally low, ranging from 39% to 55%. CONCLUSIONS: Brain and myelographic signs of spontaneous intracranial hypotension correlate poorly with CSF pressure. These findings reinforce the need to base the diagnosis of spontaneous intracranial hypotension on multiple diagnostic criteria and suggest the presence of patient-specific variables that influence CSF pressure in these individuals. PMID- 26869466 TI - Radiation Dose Reduction by Indication-Directed Focused z-Direction Coverage for Neck CT. AB - BACKGROUND AND PURPOSE: The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. MATERIALS AND METHODS: This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. RESULTS: Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. CONCLUSIONS: Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management. PMID- 26869467 TI - Prediction of Stent-Retriever Thrombectomy Outcomes by Dynamic Multidetector CT Angiography in Patients with Acute Carotid T or MCA Occlusions. AB - BACKGROUND AND PURPOSE: The selection of patients for endovascular therapy is an important issue in stroke imaging. The aim of this study was to determine the predictive value of 3 different dynamic CT angiography parameters, occlusion length, collateralization extent, and time delay to maximum enhancement, for latest generation of stent retriever thrombectomy recanalization outcomes in patients with acute ischemic stroke. MATERIALS AND METHODS: In this study, subjects were selected from an initial cohort of 2059 consecutive patients who had undergone multiparametric CT, including whole-brain CT perfusion. We included all patients with a complete occlusion of the M1 segment of the MCA or the carotid T and subsequent intra-arterial stent retriever thrombectomy. Dynamic CT angiography was reconstructed from whole-brain CT perfusion raw datasets. Angiographic outcome was scored by using the modified TICI scale; and clinical outcome, by using the modified Rankin Scale. Logistic regression analyses were performed to determine independent predictors of a favorable angiographic (mTICI = 3) and clinical outcome (mRS <=2). RESULTS: Sixty-nine patients (mean age, 68 +/- 14 years; 46% men) were included for statistical analysis. In the regression analysis, a short occlusion length was an independent predictor of favorable angiographic outcome (OR, 0.41; P < .05). Both collateralization grade (OR, 1.00; P > .05) and time delay to peak enhancement (OR, 0.90; P > .05) failed to predict a favorable angiographic outcome. None of the dynamic CT angiography predictors were significantly associated with clinical outcome on discharge (OR, 0.664 1.011; P = .330-.953) or at 90 days (OR, 0.779-1.016; P = .130-.845). CONCLUSIONS: A short occlusion length as determined by dynamic CT angiography is an independent predictor of a favorable angiographic outcome of stent retriever thrombectomy in patients with ischemic stroke. PMID- 26869468 TI - Differentiating Pediatric Rhabdomyosarcoma and Langerhans Cell Histiocytosis of the Temporal Bone by Imaging Appearance. AB - BACKGROUND AND PURPOSE: Rhabdomyosarcoma and Langerhans cell histiocytosis are malignant lesions that can affect the skull base with similar radiographic characteristics on CT and MR imaging. We hypothesized that location within the temporal bone determined radiographically can provide useful adjunctive information in differentiating these distinct neoplasms. MATERIALS AND METHODS: We identified patients with Langerhans cell histiocytosis and rhabdomyosarcoma by using an imaging data base and International Classification of Diseases, Ninth Revision codes at a tertiary care academic medical center. Cross-sectional images were reviewed by a neurotologist and neuroradiologist, who evaluated the location of the lesions and scored each subsite-middle ear, mastoid, petrous apex, retrosigmoid/posterior fossa-on a scale of 0 (no involvement), 1 (partial), or 2 (complete involvement). RESULTS: We identified 12 patients representing 14 cases of Langerhans cell histiocytosis, and 9 patients representing 9 cases of rhabdomyosarcoma. For patients with Langerhans cell histiocytosis, mastoid involvement was rated 23/28 (82%) compared with 6/18 (33%) with rhabdomyosarcoma (P = .001). Langerhans cell histiocytosis was present in only the anterior portion of the temporal bone (petrous apex and middle ear) in 1 case (7.1%) and in the anterior portion of the temporal bone only in 5/9 (55%) cases of rhabdomyosarcoma (P = .018). The cortical bone was more commonly involved in Langerhans cell histiocytosis, 11/28 (39%) of cases compared with 2/18 (11%) cases in rhabdomyosarcoma (P < .05). CONCLUSIONS: These results indicate that lesions involving only the anterior portion of the temporal bone (petrous apex and middle ear) are more likely to be rhabdomyosarcoma. Lesions involving the mastoid are more likely to be Langerhans cell histiocytosis. This difference in primary location may be helpful in predicting the pathology of these lesions on the basis of imaging. PMID- 26869469 TI - Brain MR Imaging Findings of Cardiac-Type Fabry Disease with an IVS4+919G>A Mutation. AB - BACKGROUND AND PURPOSE: A high incidence of cardiac-type Fabry disease with an alpha-galactosidase A mutation, IVS4 + 919 G>A, has been identified in the Taiwanese population. The neurologic manifestation has not been understood in this specific cardiac variant. This study aimed to investigate the typical imaging features of classic Fabry disease in patients with IVS4 Fabry disease. MATERIALS AND METHODS: Twenty-six patients with IVS4-type Fabry disease (20 men and 6 women; age range, 43-71 years; median age, 61 years) and 26 age- and sex matched healthy controls (age range, 44-68 years; median age, 60 years) were analyzed for white matter hyperintensities, the pulvinar sign, and basilar artery diameter. The volumes of white matter hyperintensities were calculated by comparison with an in-house data base of 276 controls. RESULTS: Infarctions were found in 9 patients with IVS4 Fabry disease (35%) and in none of the healthy controls (P = .001). A pulvinar sign was found in 8 patients with IVS4 Fabry disease (30%) and in none of the healthy controls (P = .002). No significant difference was found in Fazekas scale scores for white matter hyperintensities; however, white matter hyperintensity volume in the deep white matter was higher in patients with IVS4 Fabry disease than in those from the healthy control data base (P = .004). CONCLUSIONS: Along with its involvement of the cardiac system, IVS4-type Fabry disease has features similar to those of classic Fabry disease and a higher frequency of deep white matter hyperintensities and a higher incidence of infarctions and pulvinar signs than in healthy controls. PMID- 26869470 TI - The "Hyperdense Paraspinal Vein" Sign: A Marker of CSF-Venous Fistula. AB - CSF-venous fistula is a recently reported cause of spontaneous intracranial hypotension that may occur in the absence of myelographic evidence of CSF leak. Information about this entity is currently very limited, but it is of potential importance given the large percentage of cases of spontaneous intracranial hypotension associated with negative myelography findings. We report 3 additional cases of CSF-venous fistula and describe the "hyperdense paraspinal vein" sign, which may aid in its detection. PMID- 26869471 TI - New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy. AB - Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. PMID- 26869472 TI - Multicenter Prospective Trial of Stent Placement in Patients with Symptomatic High-Grade Intracranial Stenosis. AB - BACKGROUND AND PURPOSE: On the basis of the high 1-month stroke and/or death (14.7%) rates associated with stent placement in the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis trial, modifications in patient selection and procedural aspects for intracranial stent placement have been recommended. We performed a multicenter prospective single-arm trial to determine whether such modifications would result in lower rates of periprocedural stroke and/or death. MATERIALS AND METHODS: The study enrolled patients with recent transient ischemic attack or ischemic stroke (excluding perforator ischemic events) related to high-grade (70%-99% in severity) stenosis of a major intracranial artery. Patients were treated by using angioplasty and self-expanding stents 3 weeks after the index ischemic event at 1 of the 10 high-volume centers in China. An independent neurologist ascertained the occurrence of any stroke and/or death within 1 month after the procedure. RESULTS: A total of 100 consecutive patients were recruited. The target lesions were located in the middle cerebral artery (M1) (n = 38, 38%), intracranial internal carotid artery (n = 17, 17%), intradural vertebral artery (n = 18, 18%), and basilar artery (n = 27, 27%). The technical success rate of stent deployment with residual stenosis of <50% was 100%. The overall 1-month stroke and/or death rate was 2% (95% confidence interval, 0.2%-7.0%). Two ischemic strokes occurred in the pontine region (perforator distribution) in patients following angioplasty and stent placement for basilar artery stenosis. CONCLUSIONS: The results of this prospective multicenter study demonstrated that modifications in patient selection and procedural aspects can substantially reduce the 1-month stroke and/or death rate following intracranial stent placement. PMID- 26869473 TI - Relationship between M100 Auditory Evoked Response and Auditory Radiation Microstructure in 16p11.2 Deletion and Duplication Carriers. AB - BACKGROUND AND PURPOSE: Deletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency. MATERIALS AND METHODS: Thirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation. RESULTS: In controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20 ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency. CONCLUSIONS: These results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity. PMID- 26869474 TI - Development and validation of the Zurich chronic middle ear inventory (ZCMEI-21): an electronic questionnaire for assessing quality of life in patients with chronic otitis media. AB - Because existing patient-reported outcome measures (PROMs) specific for chronic otitis media (COM) are lacking certain relevant symptoms and dimensions of health related quality of life (HRQoL), we aimed to develop and validate a new questionnaire for comprehensively measuring HRQoL in adult patients with COM. An expert panel and patients were involved in developing the first version of the Zurich chronic middle ear inventory, containing 33 items (ZCMEI-33). An electronic application was chosen not only to provide maximal data quality, but also to facilitate and accelerate data analysis. Item reduction was performed by testing the questionnaire in a first cohort (n = 85). Using sequential statistical analysis, the ZCMEI-33 was reduced to 21 items (ZCMEI-21). Subsequently, the ZCMEI-21 was validated in a second cohort (n = 76). Validation revealed a Cronbach's alpha of 0.91, indicating excellent internal consistency. Moreover, the ZCMEI-21 was able to discriminate between patients with COM and healthy participants (p < 0.0001), thus possessing good discrimination validity. Assessing criterion validity, the ZCMEI-21 total score was compared to a question directly addressing HRQoL and the EQ-5D descriptive system score, a generic measure of HRQoL. Whereas the ZCMEI-21 total score and the EQ-5D descriptive system score were only moderately correlated (r = 0.60, p < 0.0001), the ZCMEI-21 total score and the question directly addressing HRQoL showed a strong correlation (r = 0.74, p < 0.0001). In conclusion, sufficient information on reliability and validity was obtained to propagate the application of the ZCMEI 21 to quantify HRQoL in patients with COM. PMID- 26869476 TI - Comparative study of millennials' (age 20-34 years) grip and lateral pinch with the norms. AB - STUDY DESIGN: Cross-sectional research design. INTRODUCTION: Clinical practice continues to use normative data for grip and pinch measurements that were established in 1985. There is no updated norms despite different hand usage patterns in today's society. PURPOSE OF THE STUDY: Measuring and comparing grip and pinch strengths with normative data is a valid method to determine hand function. This research was implemented to compare the grip and pinch measurements obtained from healthy millennials to the established norms and to describe hand usage patterns for millennials. METHODS: Grip and lateral pinch measurements were obtained from a sample of 237 healthy millennials (ages 20-34 years). RESULTS: Strength scores were statistically lower that older normative data in all millennial grip strengths, with the exception of the women in the age group of 30-34 years. Specifically, this statistically significant trend was observed in all male grip strengths, as well as in women in the age group of 20 24 years (bilateral grip) and 25-29 years (right grip). However, the lateral pinch data reflected was similar to the older norms with variances of 0.5-1 kg. CONCLUSION: Current data reflect statistically significant differences from the norms for all male grip measurements, as well as for women in the age group of 20 24 years (bilateral grip) and 25-29 years (right grip). No statistical significance was observed in the independent-sample t tests for the lateral pinch in men of all age groups. Statistical significance was noted for lateral pinch for female age groups for the left hand (20-24 years) and for bilateral lateral pinches (30-34 years). LEVEL OF EVIDENCE: IV. PMID- 26869475 TI - Stationary facial nerve paresis after surgery for recurrent parotid pleomorphic adenoma: a follow-up study of 219 cases in Denmark in the period 1985-2012. AB - The purpose was to assess degree of permanent facial nerve dysfunction after surgery for recurrent pleomorphic adenoma (RPA) of the parotid gland, including variables that might influence re-operation outcomes. Nationwide retrospective longitudinal cohort study including a questionnaire survey of patients undergoing surgery for RPA. Of 219 living patients, 198 (92 %) responded and 127 (63 %) reported no facial dysfunction. Statistically significant associations were found between number of surgeries and permanent facial nerve dysfunction of all degrees (OR 1.43, 95 % CI 1.16-1.78, p = 0.001). A not significant tendency for females to be associated with worse outcome was found (p = 0.073). Risks of different degrees of paresis after the second-fourth surgeries were found (OR 1.86-2.19, p < 0.05). Our study demonstrates a significant correlation between number of surgeries for RPA of the parotid and severity of facial nerve paresis. This is important when informing and planning treatment of these patients. PMID- 26869479 TI - Salvador Luria and Max Delbruck on Random Mutation and Fluctuation Tests. PMID- 26869477 TI - Health-related quality-of-life improvements during 98 weeks of infliximab therapy in patients with plaque-type psoriasis in real-world practice. AB - PURPOSE: We evaluated the effect of plaque-type psoriasis on health-related quality of life (HRQoL) of patients who received infliximab (IFX) in real-world clinical settings. METHODS: REALITY was a prospective, observational, open-label study of the efficacy and safety of up to 98 weeks of IFX (5 mg/kg infused at weeks 0, 2, 6, and every 8 weeks thereafter) in patients with moderate-to-severe plaque-type psoriasis. Patients with >=25 % Psoriasis Area Severity Index (PASI) improvement (PASI 25) at week 50 were eligible for the Extended Treatment Phase (treatment to week 98). Inclusion criteria were diagnosis of plaque-type psoriasis, age >=18 years, decision to start IFX, and patient consent. Key secondary efficacy outcomes included the Dermatologic Life Quality Index (DLQI; mean DLQI scores, attainment of DLQI 0/1), which was analyzed over 98 weeks. Post hoc analyses examined improvement in DLQI and the relationship between PASI and DLQI. RESULTS: In the Treatment Phase, patients (n = 516, 66.0 % men, mean age 46.4 years) had a mean baseline PASI of 18.1. Mean DLQI improved from 12.7 at baseline to 4.7 [mean change (95 % CI); -8.0 (-8.9, -7.1)] at week 50; 64.0 % (229/358) of patients improved by >=5 DLQI points. At week 50 (n = 362), 37.6 % (95 % CI; 32.7, 42.7) achieved a DLQI of 0. In the Extended Treatment Phase, patients (n = 167, 68.3 % men, mean age 46.6 years) had a mean baseline PASI of 20.4. Mean DLQI improved from 12.3 at baseline to 2.8 at week 98 [mean change (95 % CI); -9.4 (-10.8, -8.0)]; 68.6 % (96/140) of patients improved by >=5 DLQI points. At week 98 (n = 141), 47.5 % (95 % CI; 39.4, 55.7) achieved a DLQI of 0. CONCLUSIONS: Patients with plaque-type psoriasis who received treatment with IFX for 50 weeks or up to 98 weeks reported substantial HRQoL improvement. PMID- 26869478 TI - Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods. AB - Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT(+) B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods. PMID- 26869480 TI - Hermann Muller on Measuring Mutation Rates. PMID- 26869481 TI - Pick Your Poisson: An Educational Primer for Luria and Delbruck's Classic Paper. AB - The origin of beneficial mutations is fundamentally important in understanding the processes by which natural selection works. Using phage-resistant mutants in Escherichia coli as their model for identifying the origin of beneficial mutations, Luria and Delbruck distinguished between two different hypotheses. Under the first hypothesis, which they termed "acquired immunity," the phages induced bacteria to mutate to immunity; this predicts that none of the resistant mutants were present before infection by the phages. Under the second hypothesis, termed "mutation to immunity," resistant bacteria arose from random mutations independent of the presence of the phages; this predicts that resistant bacteria were present in the population before infection by the phages. These two hypotheses could be distinguished by calculating the frequencies at which resistant mutants arose in separate cultures infected at the same time and comparing these frequencies to the theoretical results under each model. The data clearly show that mutations arise at a frequency that is independent of the presence of the phages. By inference, natural selection reveals the genetic variation that is present in a population rather than inducing or causing this variation. PMID- 26869482 TI - Human Complex Trait Genetics in the 21st Century. PMID- 26869484 TI - Corrigendum. PMID- 26869483 TI - Bias-Variance Tradeoffs in Recombination Rate Estimation. AB - In 2013, we and coauthors published a paper characterizing rates of recombination within the 2.1-megabase garnet-scalloped (g-sd) region of the Drosophila melanogaster X chromosome. To extract the signal of recombination in our high throughput sequence data, we adopted a nonparametric smoothing procedure, reducing variance at the cost of biasing individual recombination rates. In doing so, we sacrificed accuracy to gain precision-precision that allowed us to detect recombination rate heterogeneity. Negotiating the bias-variance tradeoff enabled us to resolve significant variation in the frequency of crossing over across the garnet-scalloped region. PMID- 26869485 TI - Corrigendum. PMID- 26869487 TI - 3, 3', 5-triiodo-L-thyronine Increases In Vitro Chondrogenesis of Mesenchymal Stem Cells From Human Umbilical Cord Stroma Through SRC2. AB - Our group focuses on the study of mesenchymal stem cells (MSCs) from human umbilical cord stroma or Warthons jelly and their directed differentiation toward chondrocyte-like cells capable of regenerating damaged cartilage when transplanted into an injured joint. This study aimed to determine whether lactogenic hormone prolactin (PRL) or 3, 3', 5-triiodo-L-thyronine (T3), the active thyroid hormone, modulates chondrogenesis in our in vitro model of directed chondrogenic differentiation, and whether Wnt signalling is involved in this modulation. MSCs from human umbilical cord stroma underwent directed differentiation toward chondrocyte-like cells by spheroid formation. The addition of T3 to the chondrogenic medium increased the expression of genes linked to chondrogenesis like collagen type 2, integrin alpha 10 beta 1, and Sox9 measured by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Levels of collagen type 2 and aggrecane analyzed by immunohistochemistry, and staining by Safranin O were increased after 14 days in spheroid culture with T3 compared to those without T3 or only with PRL. B-catenin, Frizzled, and GSK-3beta gene expressions were significantly higher in spheroids cultured with chondrogenic medium (CM) plus T3 compared to CM alone after 14 days in culture. The increase of chondrogenic differentiation was inhibited when the cells were treated with T3 plus ML151, an inhibitor of the T3 steroid receptor. This work demonstrates, for first time, that T3 promotes differentiation towards chondrocytes-like cells in our in vitro model, that this differentiation is mediated by steroid receptor co activator 2 (SRC2) and does not induce hypertrophy. J. Cell. Biochem. 117: 2097 2108, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26869490 TI - Higher oxygen saturation targets are safer for preterm infants, trials show. PMID- 26869488 TI - Fenestrated and Chimney Technique for Juxtarenal Aortic Aneurysm: A Systematic Review and Pooled Data Analysis. AB - Juxtarenal aortic aneurysms (JAA) account for approximately 15% of abdominal aortic aneurysms. Fenestrated endovascular aneurysm repair (FEVAR) and chimney endovascular aneurysm repair (CH-EVAR) are both effective methods to treat JAAs, but the comparative effectiveness of these treatment modalities is unclear. We searched the PubMed, Medline, Embase, and Cochrane databases to identify English language articles published between January 2005 and September 2013 on management of JAA with fenestrated and chimney techniques to conduct a systematic review to compare outcomes of patients with juxtarenal aortic aneurysm (JAA) treated with the two techniques. We compared nine F-EVAR cohort studies including 542 JAA patients and 8 CH-EVAR cohorts with 158 JAA patients regarding techniques success rates, 30-day mortality, late mortality, endoleak events and secondary intervention rates. The results of this systematic review indicate that both fenestrated and chimney techniques are attractive options for JAAs treatment with encouraging early and mid-term outcomes. PMID- 26869489 TI - Taxonomist's Nightmare ... Evolutionist's Delight : An Integrative Approach Resolves Species Limits in Jumping Bristletails Despite Widespread Hybridization and Parthenogenesis. AB - Accurate species delimitation is fundamental to biology. Traditionally, species were delimited based on morphological characters, sometimes leading to taxonomic uncertainty in morphologically conserved taxa. Recently, multiple taxonomically challenging cases have benefited from integrative taxonomy-an approach that highlights congruence among different disciplines and invokes evolutionary explanations for incongruence, acknowledging that different methods can mirror different stages of the speciation continuum. Here, we used a cohesive protocol for integrative taxonomy to revise species limits in 20 nominal species and 4 morphospecies of an ancestrally wingless insect group, the jumping bristletail genus Machilis from the European Eastern Alps. Even though morphologically conserved, several small-scale endemic species have been described from the Eastern Alps based on variation in hypodermal pigmentation patterns-a highly questionable character. As valuable as these endemics are for conservation, they have never been verified by alternative methods. Using traditional morphometrics, mitochondrial DNA, ribosomal DNA, and amplified fragment-length polymorphism markers, we identify six nominal species as taxonomic junior synonyms (Machilis alpicola Janetschek, 1953 syn. n. under M. vagans Wygodzinsky, 1941; M. ladensis Janetschek, 1950 syn. n., M. robusta Wygodzinsky, 1941 syn. n., and M. vicina Wygodzinsky, 1941 syn. n. under M. inermis Wygodzinsky, 1941; M. aleamaculata Wygodzinsky, 1941 syn. n. under M. montana Wygodzinsky, 1941; M. pulchra Janetschek, 1950 syn. n. under M. helleri Verhoeff, 1910) and describe two new species (Machilis cryptoglacialis sp. n. and Machilis albida sp. n.), one uncovered from morphological crypsis and one never sampled before. Building on numerous cases of incongruence among data sources, we further shed light on complex evolutionary histories including hybrid speciation, historical and recent hybridization, and ongoing speciation. We hypothesize that an inherent affinity to hybridization, combined with parallel switches to parthenogenesis and repeated postglacial colonization events may have boosted endemicity in Eastern Alpine Machilis We thus emphasize the importance of integrative taxonomy for rigorous species delimitation and its implication for evolutionary research and conservation in taxonomically challenging taxa. PMID- 26869492 TI - Current management options for displaced intra-articular calcaneal fractures: Non operative, ORIF, minimally invasive reduction and fixation or primary ORIF and subtalar arthrodesis. A contemporary review. AB - BACKGROUND: Management of Displaced Intra-articular Calcaneal Fractures (DIACFs) continues to be technically demanding. The literature has not been definitive in its guidance for surgeons dealing with these injuries. Recent publications have further added to the lack of clarity. This review is intended to summarise the present state of knowledge, and provide some genuine guidance for clinicians. OBJECTIVES: To review previous research, focussing on articles published within the last fifteen years, and summarise the findings to aid surgeons in managing DIACFs with choosing best management for patients. METHODS: We reviewed the best evidence and literature, focussing on articles published within the last fifteen years, and summarised findings into workable recommendations. Variables of (1) patient, (2) the associated soft tissue injury and (3) the fracture characteristics were used to aid surgeons in choosing the best of the available options for each patient that presents with a DIACF. AUTHORS SUMMARY: Management of DIACFs can best be divided into four broad categories: (i) non-operative management, (ii) open reduction and internal fixation, (iii) minimally invasive reduction and fixation, and (iv) primary subtalar arthrodesis. The evolution of the literature would suggest orthopaedic surgeons managing calcaneus fractures should have an expert's knowledge, surgical expertise and the latest techniques to cover these four options, to tailor the treatment of DIACFs to the individual patient. PMID- 26869491 TI - Overexpression of RNF2 Is an Independent Predictor of Outcome in Patients with Urothelial Carcinoma of the Bladder Undergoing Radical Cystectomy. AB - RNF2 (ring finger protein 2) is frequently overexpressed in several types of human cancer, but the status of RNF2 amplification and expression in urothelial carcinoma of the bladder (UCB) and its clinical/prognostic significance is unclear. In this study, immunohistochemical analysis and fluorescence in situ hybridization (FISH) were used to examine the expression and amplification of RNF2 in 184 UCB patients after radical cystectomy. Overexpression of RNF2 was observed in 44.0% of UCBs and was found to significantly associate with shortened overall and cancer-specific survival (P < 0.001). In different subsets of UCBs, RNF2 overexpression was also identified as a prognostic indicator in patients with pT1, pT2, pN(-), and/or negative surgical margins (P < 0.05). Importantly, RNF2 overexpression together with pT status and surgical margin status provided significant independent prognostic parameters in multivariate analysis (P < 0.01). FISH results showed amplification of RNF2 in 8/79 (10.1%) of informative UCB cases. Additionally, RNF2 overexpression was significantly associated with RNF2 gene amplification (P = 0.004) and cell proliferation (P = 0.003). These findings suggested that overexpression of RNF2, as examined by immunohistochemical analysis, might serve as a novel prognostic biomarker and potential therapeutic target for UCB patients who undergo radical cystectomy. PMID- 26869493 TI - What factors predict the need for further intervention following corticosteroid injection of Morton's neuroma? AB - BACKGROUND: This study investigated factors that may predict the need for Morton's neuroma (MN) to undergo further treatment within 2 years of a single ultrasound-guided corticosteroid injection. METHODS: A retrospective study was undertaken over a three-year period. The data was stratified into two groups: Group A - did not receive further intervention and Group B - received further treatment. We investigated age, gender, neuroma size and presence of other forefoot pathology or ipsilateral neuromas. RESULTS: 54 patients (57 feet) were reviewed. 29 feet (51%) required further treatment within 2 years (11 repeat injections, 18 surgical excisions). Binary logistic regression showed that larger neuromas (p=0.011) and younger patients (p=0.007) predicted the need for further intervention but not gender (p=0.272). The distribution of concomitant forefoot pathology and ipsilateral neuromas were similar between the two groups. CONCLUSION: Size and age appear to be predictors for further treatment of MN within 2 years of corticosteroid injection. PMID- 26869494 TI - Distraction osteogenesis of fourth brachymetatarsia. AB - BACKGROUND: Brachymetatarsia is a rare congenital or developmental condition that results in a short metatarsal. The condition most commonly affects the fourth metatarsal of young and adolescent females. It does not usually produce a functional problem. However, it may produce a significant cosmetic problem especially in young women. The authors present their experience in gradual distraction of the fourth metatarsal to tackle this problem in adults. METHODS: That was done using a monolateral frame in 11 feet of female patients with an average age of 23 years. Evaluation depended upon the achievement of the target length, angulation, pain, and satisfaction of the patient. RESULTS: There were eight excellent and three good results after an average follow up of 2.6 years. Aside from nine cases of mild pin-tract infection, complications were few and minor. CONCLUSIONS: We recommend distraction osteogenesis as the treatment of choice for brachymetatarsia of the fourth toe. PMID- 26869495 TI - Midfoot arthrodesis. AB - BACKGROUND: Surgery for midfoot arthritis is challenging and technically demanding, especially in the presence of deformity. METHODS: Thirty patients (30 feet) with symptomatic midfoot arthritis and deformities, underwent arthrodesis, along with adjuvant procedures to realign the hindfoot and forefoot where needed. RESULTS: Union was achieved in 28 out of 30 (93.3%) patients. Mean time to union was 12.9 weeks (range 10-18). Five patients (16.6%) developed postoperative complications and six patients (20%) required unplanned surgical procedures. Orthotics was needed postoperatively in 14 patients (34%). Fourteen out of 30 patients rated their outcome as excellent (47%), 13 out of 30 as good (43%) and 3 out of 30 (10%) as fair or poor. CONCLUSIONS: Although the vast majority of patients rated their outcome as good or excellent, the foot is not completely normal, with residual pain from the adjacent joints, need for unplanned surgery and use of orthotics postoperatively. PMID- 26869496 TI - Open wedge metatarsal osteotomy versus crescentic osteotomy to correct severe hallux valgus deformity - A prospective comparative study. AB - BACKGROUND: Different techniques of proximal osteotomies have been introduced to correct severe hallux valgus. The open wedge osteotomy is a newly introduced method for proximal osteotomy. The aim of this prospective randomized study was to compare the radiological and clinical results after operation for severe hallux valgus, comparing the open wedge osteotomy to the crescentic osteotomy which is our traditional treatment. METHODS: Forty-five patients with severe hallux valgus (hallux valgus angle >35, and intermetatarsal angle >15) were included in this study. The treatment was proximal open wedge osteotomy and fixation with plate (Hemax), group 1, or operation with proximal crescentic osteotomy and fixation with a 3mm cannulated screw, group 2. The mean age was 52 years (19-71). Forty-one females and four males were included. Clinical and radiological follow-ups were performed 4 and 12 months after the operation. RESULTS: In group 1 the hallux valgus angle decreased from 39.0 to 24.1 after 4 months and 27.9 after 12 months. In group 2 the angle decreased from 38.3 to 21.4 after 4 months and 27.0 after 12 months. The intermetatarsal angle in group 1 was 19.0 preoperatively, 11.6 after 4 months and 12.6 after 12 months. In group 2 the mean intermetatarsal angle was 18.9 preoperatively, 12.0 after 4 months and 12.6 after 12 months. The AOFAS score improved from 59.3 to 81.5 in group 1 and from 61.8 to 84.8 in group 2 respectively measured 12 months postoperatively. The relative length of the 1 metatarsal compared to 2 metatarsal bone was 0.88 and 0.87 preoperatively and 0.88 and 0.86 for group 1 and 2 respectively measured after 12 months. CONCLUSION: Crescentic osteotomy and open wedge osteotomy improve AOFAS score and VAS scores on patients operated with severe hallux valgus. No significant difference was found in the two groups looking at the postoperative improvement of HVA and IMA measured 4 and 12 months postoperatively. The postoperative VAS score and AOFAS score were comparable for the two groups with no significant difference. An expected tendency to gain better length of the first metatarsal using the open wedge osteotomy compared to the crescentic osteotomy was not found. Even though the IMA and HVA reduction was only suboptimal the improvement in AOFAS score was comparable to other similar clinical trials. PMID- 26869497 TI - Total ankle replacement and contralateral ankle arthrodesis in 16 patients from the Swedish Ankle Registry: Self-reported function and satisfaction. AB - BACKGROUND: Both total ankle replacement (TAR) and ankle arthrodesis do show some problems in long-term studies. To choose either of these surgical options is a delicate task. There are no randomized studies reported in the literature and no previous studies in which patients constitute the own controls. METHODS: Patients with a TAR and a contralateral ankle arthrodesis were identified in the Swedish Ankle Register. A self-reported foot and ankle specific questionnaire (SEFAS) was sent to these patients who also were asked to report their grade of satisfaction from 1 to 5. RESULTS: The median SEFAS score was 32 (16-44) for the prostheses and 27 (14-47) for the arthrodeses. The median satisfaction score was 2 (1-4) for the prostheses and 2 (1-5) for the arthrodeses. There were no statistically significant difference between the prosthetic side and the fused side regarding these scores. CONCLUSION: Patients who had undergone ankle arthrodesis on one side and had the contralateral ankle replaced, were equally satisfied with both procedures. PMID- 26869498 TI - The effect of posture on the osseous relations in the foot. AB - BACKGROUND: Discrepancies observed between clinical findings and a weightbearing foot X-ray might be caused by a patients' positioning. This study's main objective was to determine the effect of a subjects' posture on the osseous relations of the foot. METHODS: Anatomical markers were placed on the skin of the foot of 17 subjects. A plantar pressure plate assessed the percentage weight on the foot and weight distribution over the foot. Medial longitudinal foot angles were derived from the markers and compared between the 10 postures. The effect of percentage weight and weight distribution on the foot angles was determined by multiple regression analysis. RESULTS: The foot angles were significantly affected by the postures. The multiple regression analysis revealed the weight on the foot and the mediolateral weight distribution over the foot as important factors for the foot angles. CONCLUSION: A subjects posture significantly influences the osseous relations in the foot. PMID- 26869499 TI - The peroneus brevis tendon at its insertion site on fifth metatarsal bone. AB - BACKGROUND: The differences at the attachment site of peroneus brevis (PB) to the fifth metatarsal bone is important in terms of the forces exerted on the bone and hence the mechanism of fractures involving this structure. In this study, we investigated the anatomical properties of PB at the insertion site to the base of fifth metatarsal bone, its possible intertendinous connections with peroneus tertius (PT) and their possible effects on the fracture occurrence at the bony attachment site. METHODS: The length and the width of PB tendons at their mid- and end-points were measured and classified according to the insertion types. Besides, the length and the width of the base of fifth metatarsal bone were assessed. The slips extending from the PB tendons and their relationship with PT were also evaluated. The data was compared statistically with each other and between the right and left sides. RESULTS: The length of PB tendon was measured 79.57+/-15.40mm on the right side; 81.48+/-14.31mm on the left. The width of PB tendon at the mid-point was 4.46+/-0.80mm on the right side; 4.42+/-0.94mm on the left. The width of the tendon at its insertion point was measured 14.85+/-3.40mm and 15.16+/-3.42mm on the right and left sides respectively. PB was divided into three types according to its attachment to base of fifth metatarsal bone (5thMB). Type I, Type II and Type III were observed at the rates of 59.5%, 28.6% and 11.5% respectively. It was observed that the slips to the bone were extending more commonly from PB than from PT and that the large majority of them were single having their insertions on the base of the proximal phalanx of the fifth toe. CONCLUSIONS: Knowing the width and insertional types of PB aids in understanding the mechanism of fractures at the site of bony attachment. The existence of slips may help the surgeon in the procedures involving PB or the lateral side of the forefoot. PMID- 26869500 TI - Is it too early to move to full electronic PROM data collection?: A randomized controlled trial comparing PROM's after hallux valgus captured by e-mail, traditional mail and telephone. AB - BACKGROUND: Patient reported outcome measures (PROM's) after hallux valgus surgery are used to rate the effectiveness as perceived by the patient. The interpretability of these PROM's is highly dependent on participation rate. Data capture method may be an important factor contributing to the response rate. We investigated the effect on response rate of traditional paper mail, telephone and e-mail PROM's after hallux valgus surgery. METHODS: All consecutive patients operated between January and September 2013, were identified. Included patients were randomized by envelope in three groups: traditional pen and paper mail, e mail and telephone. They were asked to fill in a FFI and EQ-5D. Two weeks later non-responders were sent a reminder. RESULTS: Of the 73 included patients, 25 were approached by mail, 24 by e-mail and 24 patients by telephone. The response rate on traditional mail was highest (88%), while response on e-mail was lowest (33%). Response rate on telephone was also high (79%). Response rate on traditional mail and telephone was significantly higher (p<0.001) than response on e-mail. CONCLUSIONS: Though electronic data collection has enormous potential, this study shows that e-mail yields unacceptable low response rates. It is too early to replace traditional pen-and-paper PROM's by electronic questionnaires. PMID- 26869501 TI - Biomechanical evaluation of a second generation headless compression screw for ankle arthrodesis in a cadaver model. AB - BACKGROUND: Many types of screws, plates, and strut grafts have been utilized for ankle arthrodesis. Biomechanical testing has shown that these constructs can have variable stiffness. More recently, headless compression screws have emerged as an evolving method of achieving compression in various applications but there is limited literature regarding ankle arthrodesis. The aim of this study was to determine the biomechanical stability provided by a second generation fully threaded headless compression screw compared to a standard headed, partially threaded cancellous screw in a cadaveric ankle arthrodesis model. MATERIALS AND METHODS: Twenty fresh frozen human cadaver specimens were subjected to simulated ankle arthrodesis with either three standard cancellous-bone screws (InFix 7.3mm) or with three headless compression screws (Acumed Acutrak 2 7.5mm). The specimens were subjected to cyclic loading and unloading at a rate of 1Hz, compression of 525 Newtons (N) and distraction of 20N for a total of 500 cycles using an electromechanical load frame (Instron). The amount of maximum distraction was recorded as well as the amount of motion that occurred through 1, 10, 50, 100, and 500 cycles. RESULTS: No significant difference (p=0.412) was seen in the amount of distraction that occurred across the fusion site for either screw. The average maximum distraction after 500 cycles was 201.9MUm for the Acutrak 2 screw and 235.4MUm for the InFix screw. No difference was seen throughout each cycle over time for the Acutrak 2 screw (p-value=0.988) or the InFix screw (p value=0.991). CONCLUSION: Both the traditional InFix type screw and the second generation Acumed Acutrak headless compression screws provide adequate fixation during ankle arthrodesis under submaximal loads. CLINICAL RELEVANCE: There is no demonstrable difference between traditional cannulated partially threaded screws and headless compression screws studied in this model. PMID- 26869502 TI - Clinical profile and surgical management of diabetic foot in Benghazi, Libya. AB - BACKGROUND: The aim of this study was to outline the patterns and management of diabetic foot ulcer (DFU) and compare our experience with other published data. PATIENTS AND METHODS: All consecutive patients admitted to Al-Jala Hospital with diabetic foot from June, 2008 to May, 2013 were reviewed retrospectively. RESULTS: A total of 542 patients were studied, Wagner's grade III ulcers were the most prevalent (31%), followed by grade II (25%). About 10% of patients underwent major amputations and 24.2% underwent minor amputations. The amputation rate was 34%, and the mortality rate was 2%. CONCLUSION: Diabetic foot infections cause significant morbidity and mortality among patients with diabetes in Benghazi. There is a need to establish a diabetic foot clinic in Benghazi with a multidisciplinary team to reduce the rates of hospital admission and amputation, as well as hospital stay duration. PMID- 26869503 TI - Reliability, validity and responsiveness of the Spanish Manchester-Oxford Foot Questionnaire (MOXFQ) in patients with foot or ankle surgery. AB - BACKGROUND: The Manchester-Oxford Foot Questionnaire (MOXFQ) has been validated in Spanish for use in patients undergoing foot and ankle surgery. METHODS: 120 patients completed the MOXFQ and the SF-36 before surgery and 6 and 12 months postoperative. Surgeons completed the American Orthopaedic Foot and Ankle Society (AOFAS) Clinical Rating System. Psychometric properties were assessed for all three MOXFQ dimensions, and for the MOXFQ Index. RESULTS: The Spanish MOXFQ demonstrated consistency with Cronbach's alpha values between 0.65 and 0.90, and reliability ([ICCs] >0.95). It shows a moderate to strong correlation between the Walking/standing dimension and the related domains of the SF-36 (|r|>0.6), the AOFAS Ankle-Hindfoot Scale (|r|>0.47) and Hallux-MTP-IP Scale (|r|>0.64). Responsiveness was excellent, (effect sizes >2.1). The respective minimal detectable change (MDC90) was 14.18 for the MOXFQ Index. CONCLUSIONS: The Spanish version of the MOXFQ showed good psychometric properties in patients with foot and ankle disorders. PMID- 26869504 TI - Flexion of the foot changes tension on the anterior neurovascular bundle. PMID- 26869506 TI - Remnant-preserving, selective single-bundle augmentation of the anterior cruciate ligament using a bone-patellar tendon-bone autograft: A technical note. AB - BACKGROUND: To the best of our knowledge, there has been no detailed study on bone-patellar tendon-bone (BTB) grafts for remnant-preserving, selective-bundle anterior cruciate ligament (ACL) augmentation. Therefore, we aimed to develop such a technique using a BTB graft. METHOD: A total of five patients underwent surgery using the presented procedure. These patients were young, male, and with high body mass index, and hence required very high durability of reconstructed ACL. A femoral bone tunnel was created using the inside-out technique via an accessory far-medial portal, protecting the remnant using a probe, regardless of the presence of an anteromedial (AM) or posterolateral (PL) tunnel. A single tibial tunnel was drilled at the center of the AM or PL attachment and two transverse skin incisions were made in the ipsilateral knee. The central third of the patellar tendon attached to a patellar and tibial bone plug autograft with a width of seven millimeters was harvested by subcutaneous tunneling. The femoral side was fixed using a cortical fixation device for BTB and the tibial bone plug was fixed using an interference screw with the knee at an angle of 20 degrees of flexion by applying maximal manual traction. RESULTS: Bone tunnel enlargement, which was measured by computed digital radiography, was not observed in all cases. A BTB autograft for remnant-preserving, selective-bundle ACL augmentation offers reduced risk of tunnel enlargement. CONCLUSION: The presented procedure might be considered one of the potentially available options for patients with ACL partial tear who require very high durability of reconstructed ACL. LEVEL OF EVIDENCE: 5. PMID- 26869507 TI - Successful Treatment of Hepatitis C Infection While Receiving Concurrent Chemotherapy for AL Amyloidosis. PMID- 26869508 TI - Residual force enhancement following shortening is speed-dependent. AB - The steady-state isometric force following active muscle shortening or lengthening is smaller (force depression; FD) or greater (residual force enhancement; RFE) than a purely isometric contraction at the corresponding length. The mechanisms underlying these phenomena are not explained within the context of the cross-bridge theory and are rarely studied in concert. Previous studies have shown RFE to be speed-independent. In the present study, we investigated if RFE preceded by active shortening is time-dependent by electrically evoking RFE in the human adductor pollicis muscle. The results shown that a slow stretch following FD fully re-established RFE compared to higher speeds of stretch. The mechanism(s) responsible for the recovery of RFE following a preceding shortening contraction (FD) might be associated with the recovery of cross-bridge based force and/or the re-engagement of a passive structural element (titin). Voluntary interaction with one's environment involves highly coordinated shortening and lengthening muscle contractions. Therefore comprehending these history-dependent muscle properties in the context of movement control is paramount in understanding the behavior of in vivo motor control. PMID- 26869505 TI - The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems. AB - The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems. PMID- 26869509 TI - Tessaracoccus flavus sp. nov., isolated from the drainage system of a lindane producing factory. AB - Strain RP1T, a Gram-stain-positive, non-motile, non-spore-forming, coccus-shaped bacterium, was isolated from drainage of India Pesticides Limited, a lindane producing unit situated at Chinhat, Lucknow, India. 16S rRNA gene sequence analysis revealed that strain RP1T belongs to the family Propionibacteriaceae and was closely related to the members of the genus Tessaracoccus with a similarity range of 95.4-97.6%. Strain RP1T was facultatively anaerobic, oxidase-negative, catalase-positive and capable of nitrate reduction. Strain RP1T contained peptidoglycan type A3gamma', with ll-diaminopimelic acid as the diagnostic diamino acid and glycine at position 1 of the peptide subunit. The major cellular fatty acid of strain RP1T was anteiso-C15 : 0 but a significant amount of iso C14:0 was also detected. MK-9(H4) was the major respiratory quinone and polyamines detected were spermine and spermidine. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, two unknown glycolipids and two unknown phospholipids. The G+C content of the DNA was 66.7 mol%. The levels of DNA-DNA relatedness between RP1T and Tessaracoccus lubricantis KSS-17SeT, Tessaracoccus oleiagri SL014B-20A1T and Tessaracoccus flavescens SST-39T were 49.8, 34.8 and 23.5%, respectively. Based on the phenotypic and phylogenetic data presented, strain RP1T can be differentiated from previously described species of the genus Tessaracoccus, and thus represents a novel species, for which the name Tessaracoccus flavus sp. nov. is proposed. The type strain is RP1T (=DSM 100159T=MCC 2769T=KCTC 39686T). PMID- 26869510 TI - Effects of forage offering method on performance, rumen fermentation, nutrient digestibility and nutritional behaviour in Holstein dairy calves. AB - The potential effect of dietary forage supplementation on the performance and rumen development in dairy calves is well established. However, limited research has been directed to the comparative effects of forage offering methods on calf performance. The objective of the present study was to determine the effects of forage provision methods (total mixed ration or free choice) on the performance, nutrient digestibility, rumen fermentation and nutritional behaviour in newborn calves. Forty-five Holstein dairy calves (3 days of age and 41 +/- 2 kg of body weight) were assigned to the following three groups (n = 15): (i) starter without forage provision (CON), (ii) starter supplemented with 10% alfalfa hay (AH) as a total mixed ration (AH-TMR) and (iii) starter and AH as a free-choice provision (AH-FC) for a period of 70 days. All the calves were offered 5 l of milk/day from day 3 to 50, and 2.5 l/day from day 50 until weaning on day 56. Dry matter intake (DMI) was greater (p < 0.01) in the AH-TMR and AH-FC treatments than in the CON during the pre- and post-weaning periods. Calves fed the AH-FC diet showed the highest post-weaning DMI among the treatments. The calves receiving ad libitum forage tended (p = 0.08) to increase crude protein digestibility and overall volatile fatty acids (VFA) concentrations in the rumen. No differences were observed among the treatments at the time spent on standing, lying, eating and performing non-nutritive oral behaviours. Compared to CON calves, animals in the AH-TMR treatment spent more time (p < 0.05) ruminating. In conclusion, our data suggest that forage supplementation in both forage offering methods increased total DMI, ruminal pH and ruminating time in dairy calves. Hence, there is no benefit in the free-choice provision of AH in dairy calves. PMID- 26869511 TI - Large-scale proteome analysis of abscisic acid and ABSCISIC ACID INSENSITIVE3 dependent proteins related to desiccation tolerance in Physcomitrella patens. AB - Desiccation tolerance is an ancestral feature of land plants and is still retained in non-vascular plants such as bryophytes and some vascular plants. However, except for seeds and spores, this trait is absent in vegetative tissues of vascular plants. Although many studies have focused on understanding the molecular basis underlying desiccation tolerance using transcriptome and proteome approaches, the critical molecular differences between desiccation tolerant plants and non-desiccation plants are still not clear. The moss Physcomitrella patens cannot survive rapid desiccation under laboratory conditions, but if cells of the protonemata are treated by the phytohormone abscisic acid (ABA) prior to desiccation, it can survive 24 h exposure to desiccation and regrow after rehydration. The desiccation tolerance induced by ABA (AiDT) is specific to this hormone, but also depends on a plant transcription factor ABSCISIC ACID INSENSITIVE3 (ABI3). Here we report the comparative proteomic analysis of AiDT between wild type and ABI3 deleted mutant (Deltaabi3) of P. patens using iTRAQ (Isobaric Tags for Relative and Absolute Quantification). From a total of 1980 unique proteins that we identified, only 16 proteins are significantly altered in Deltaabi3 compared to wild type after desiccation following ABA treatment. Among this group, three of the four proteins that were severely affected in Deltaabi3 tissue were Arabidopsis orthologous genes, which were expressed in maturing seeds under the regulation of ABI3. These included a Group 1 late embryogenesis abundant (LEA) protein, a short-chain dehydrogenase, and a desiccation-related protein. Our results suggest that at least three of these proteins expressed in desiccation tolerant cells of both Arabidopsis and the moss are very likely to play important roles in acquisition of desiccation tolerance in land plants. Furthermore, our results suggest that the regulatory machinery of ABA- and ABI3 mediated gene expression for desiccation tolerance might have evolved in ancestral land plants before the separation of bryophytes and vascular plants. PMID- 26869512 TI - Genome-wide survey of Aux/IAA gene family members in potato (Solanum tuberosum): Identification, expression analysis, and evaluation of their roles in tuber development. AB - The Auxin/indole-3-acetic acid (Aux/IAA) genes encode short-lived nuclear proteins that are known to be involved in the primary cellular responses to auxin. To date, systematic analysis of the Aux/IAA genes in potato (Solanum tuberosum) has not been conducted. In this study, a total of 26 potato Aux/IAA genes were identified (designated from StIAA1 to StIAA26), and the distribution of four conserved domains shared by the StIAAs were analyzed based on multiple sequence alignment and a motif-based sequence analysis. A phylogenetic analysis of the Aux/IAA gene families of potato and Arabidopsis was also conducted. In order to assess the roles of StIAA genes in tuber development, the results of RNA seq studies were reformatted to analyze the expression patterns of StIAA genes, and then verified by quantitative real-time PCR. A large number of StIAA genes (12 genes) were highly expressed in stolon organs and in during the tuber initiation and expansion developmental stages, and most of these genes were responsive to indoleacetic acid treatment. Our results suggested that StIAA genes were involved in the process of tuber development and provided insights into functional roles of potato Aux/IAA genes. PMID- 26869513 TI - In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats. AB - The skin is the largest organ in the body and diabetes induces pathologic changes on the skin that affect glucose homeostasis. Changes in skin glycogen and glucose levels can mirror serum glucose levels and thus the skin might contribute to whole body glucose metabolism. This study investigated the in vivo effects of diabetes, insulin and oleanolic acid (OA) on enzymes of glycogen metabolism in skin of type 1 diabetic rats. Diabetic and non-diabetic adult male Sprague-Dawley rats were treated with a single daily dose of insulin (4 IU/kg body weight), OA (80 mg/kg body weight) and a combination of OA + insulin for 14 days. Glycogen phosphorylase (GP) expression; and GP, glycogen synthase (GS) and hexokinase activities as well glycogen levels were evaluated. The results suggest that diabetes lowers hexokinase activity, GP activity and GP expression with no change in GS activity whilst the treatments increased GP expression and the activities of hexokinase, GP and GS except for the GS activity in OA treated rats. Glycogen levels were increased slightly by diabetes as well as OA treatment. In conclusion diabetes, OA and insulin can lead to changes in GS and GP activities in skin without significantly altering the glycogen content. We suggest that the skin may contribute to whole body glucose homeostasis particularly in disease states. PMID- 26869514 TI - Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation. AB - The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. PMID- 26869515 TI - Ethyl-2, 5-dihydroxybenzoate displays dual activity by promoting osteoblast differentiation and inhibiting osteoclast differentiation. AB - The interplay between bone-forming osteoblasts and bone-resorbing osteoclasts is essential for balanced bone remodeling. In this study, we evaluate the ability of ethyl-2, 5-dihyrdoxybenzoate (E-2, 5-DHB) to affect both osteoblast and osteoclast differentiation for bone regeneration. Osteogenic differentiation of human mesenchymal stem cells (hMSCs) was quantified by measuring alkaline phosphatase (ALP) activity and calcium deposition. To evaluate osteoclast differentiation, we investigated the effect of E-2, 5-DHB on RANKL-activated osteoclastogenesis in RAW 264.7 cells. E-2, 5-DHB enhanced ALP activity and inhibited RAW 264.7 cell osteoclastogenesis in vitro. To assess the in vivo activity of E-2, 5-DHB, hMSCs were delivered subcutaneosuly alone or in combination with E-2, 5-DHB in an alginate gel into the backs of nude-mice. Histological and immunohistochemical evaluation showed significantly higher calcium deposition in the E-2, 5-DHB group. Osteocalcin (OCN) was highly expressed in cells implanted in the gels containing E-2, 5-DHB. Our results suggest that E-2, 5-DHB can effectively enhance osteoblast differentiation and inhibit osteoclast differentiation both in vitro and in vivo. Understanding the dual function of E-2, 5-DHB on osteoblast and osteoclast differentiation will aid in future development of E-2, 5-DHB as a material for bone tissue engineering. PMID- 26869517 TI - Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors. AB - Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (>=10(-5) M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Upsilon (PPARUpsilon). Notably, rosiglitazone also stimulates RPT cell growth, as does Upsilon-linolenic acids, another PPARUpsilon agonist. The PPARUpsilon antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARUpsilon as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. PMID- 26869516 TI - Recognition of alternatively spliced cassette exons based on a hybrid model. AB - Alternative splicing (AS) is an important mechanism of gene regulation that contributes to protein diversity. It is of great significance to recognize different kinds of AS accurately so as to understand the mechanism of gene regulation. Many in silico methods have been applied to detecting AS with vast features, but the result is far from satisfactory. In this paper, we used the features proven to be useful in recognizing AS in previous literature and proposed a hybrid method combining Gene Expression Programming (GEP) and Random Forests (RF) to classify the constitutive exons and cassette exons which is the most common AS phenomenon. GEP will firstly make prediction to the samples of strong signal, and the other samples of weak signal will be distinguished with a more complex classifier based on RF. The experiment result indicates that this method can highly improve the recognition level in this issue. PMID- 26869518 TI - Advances made in resuscitation: current status. PMID- 26869519 TI - Patterns of surgical presentation at an African regional referral hospital: surveillance as a step towards improving access to care. AB - PURPOSE: Surgical disease is being increasingly recognized as a significant health burden in Africa. Efforts have been made to describe surgical disease and capacity at the district hospital level. Little is known about patterns seen at regional hospitals supporting the district hospital network. METHODS: This retrospective study was conducted at Uganda's Soroti Regional Referral Hospital, serving eight districts. Data were collected from July 2010 to March 2012 using operative and inpatient records as available. Univariate and bivariate analyses were performed to explore patterns of procedures performed and in-patient diagnoses. RESULTS: There were 8511 procedures recorded in the operative log between July 2010 and June 2011, averaging 709 per month. Caesarian sections (41 %), dilation and evacuations (28 %), and laparotomies (19 %) were most frequent. Referrals to Soroti averaged 260 per month, while transfers out averaged 5 patients per month. Inpatient records documented 2949 surgically related diagnoses between July 2010 and May 2011. In patients >4 years old, 21 % of mortality was due to surgical disease, 29 % of which was trauma-related. Women comprised 80 % of violent injury. Common hospital record elements, such as demographic data, important clinical information, and operative notes were absent from these data sources. CONCLUSIONS: The World Health Assembly recently recognized strengthening of first referral hospitals as a crucial element to achieving universal health coverage. Inconsistencies in recordkeeping despite the large volume of surgical disease suggest that sustainable surveillance systems and capacity building at the referral hospital level are potential building blocks to improving access to surgical care. PMID- 26869520 TI - Impacts of manure application on soil environment, rainfall use efficiency and crop biomass under dryland farming. AB - Because of inadequate nutrient and water supply, soils are often unproductive in Northwest China. We studied the effects of manure application at low (LM 7.5 t ha(-1)), medium (MM 15 t ha(-1)), and high (HM 22.5 t ha(-1)) rates combined with fixed levels of chemical fertilizers on maize growth and rainfall use efficiency compared with chemical fertilizers (CK) under semi-arid conditions over a three year period. HM and MM treatments could significantly increase soil water storage (0-120 cm) at tasseling stage of maize compared with LM treatment and CK (P < 0.05). Dry matter accumulation and rainfall use efficiency increased as manure application rate increasing (P < 0.05). HM treatment significantly increased rainfall use efficiency by 6.5-12.7% at big trumpeting - tasseling stage compared with LM and MM treatments. HM and MM treatments increased rainfall use efficiency by 8.6-18.1% at tasseling - grain filling stage compared with CK. There was no significant difference on biomass between HM and MM treatments at grain filling and maturity stages of maize in 2009 and 2010. PMID- 26869521 TI - Spondylodiscitis. AB - Spondylodiscitis is an infection of the spine that has been known since ancient times. Its incidence is rising, due to the increases in life expectancy and debilitating conditions. Its age distribution is bimodal, affecting persons younger than 20 years of age or persons aged 50-70 years. According to its origin, it is classified as pyogenic, granulomatous or parasitic, though the first form is the most common, usually caused by Staphylococcus aureus or Escherichia coli. The clinical presentation is insidious, resulting in a delayed diagnosis, particularly in tuberculous spondylodiscitis. The initial onset usually involves inflammatory back pain, though the disease may course with fever, asthenia and neurological deficit, these being the most severe complications. Diagnosis is based on clinical, radiological, laboratory, microbiological and histopathological data. Magnetic resonance imaging is the technique of choice for the diagnosis of spondylodiscitis. The differential diagnosis involves, among other conditions, intervertebral erosive osteochondrosis, tumour, axial spondyloarthropathy, haemodialysis spondyloarthropathy, Modic type 1 endplate changes and Charcot's axial neuroarthropathy. Treatment is based on eliminating the infection with antibiotics, preventing spinal instability with vertebral fixation, and ample debridement of infected tissue to obtain samples for analysis. PMID- 26869522 TI - Case of ovarian hyperstimulation and oocyte pick-up during very early period of unnoticed pregnancy followed by ongoing normal pregnancy. AB - We report a case of unnoticed pregnancy that was maintained during low estrogen and progesterone circumstances, that showed menses-like bleeding, and was then discovered after ovarian hyperstimulation during the next period. The patient was 39 years old and primigravid. She underwent intrauterine insemination, followed by luteal support with human chorionic gonadotrophin and progestin; however, she experienced menstruation-like bleeding 15 days later. As low estradiol and progesterone levels were confirmed on the 2nd day of bleeding, ovarian hyperstimulation of short protocol for in vitro fertilization was commenced. Although 13 mature follicles were observed, only six oocytes were retrieved and one developed into a blastocyst. Four days after oocyte pick-up, a gestational sac was seen in utero. The fetus is currently growing uneventfully. This case suggests that pregnancy can be maintained during ovarian hyperstimulation, even if menstruation-like bleeding is shown in low-progesterone circumstances. PMID- 26869523 TI - Aspirin-Triggered Resolvin D1 Inhibits TGF-beta1-Induced EndMT through Increasing the Expression of Smad7 and Is Closely Related to Oxidative Stress. AB - The endothelial-mesenchymal transition (EndMT) is known to be involved in the transformation of vascular endothelial cells to mesenchymal cells. EndMT has been confirmedthat occur in various pathologic conditions. Transforming growth factor beta1 (TGF-beta1) is a potent stimulator of the vascular endothelial to mesenchymal transition (EMT). Aspirin-triggered resolvin D1 (ATRvD1) has been known to be involved in the resolution of inflammation,but whether it has effects on TGF-beta1-induced EndMT is not yet clear. Therefore, we investigated the effects of AT-RvD1 on the EndMT of human umbilical vein vascular endothelial cells line (HUVECs). Treatment with TGF-beta1 reduced the expression of Nrf2 and enhanced the level of F-actin, which is associated with paracellular permeability. The expression of endothelial marker VE-cadherin in HUVEC cells was reduced, and the expression of mesenchymal marker vimentin was enhanced. AT-RvD1 restored the expression of Nrf2 and vimentin and enhanced the expression of VE cadherin. AT-RvD1 did also affect the migration of HUVEC cells. Inhibitory kappaB kinase 16 (IKK 16), which is known to inhibit the NF-kB pathway, had an ability to increase the expression of Nrf2 and was associated with the inhibition effect of AT-RvD1 on TGF-beta1-induced EndMT, but it had no effect on TGF-beta1-induced EndMT alone. Smad7, which is a key regulator of TGF-beta/Smads signaling by negative feedback loops, was significantlyincreased with the treatment of AT RvD1. These results suggest the possibility that AT-RvD1 suppresses the TGF-beta1 induced EndMT through increasing the expression of Smad7 and is closely related to oxidative stress. PMID- 26869524 TI - Long-Duration Three-Dimensional Spheroid Culture Promotes Angiogenic Activities of Adipose-Derived Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine. PMID- 26869525 TI - iRhoms; Its Functions and Essential Roles. AB - In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and traffickingof tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarifiedthat the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease. Thus, this review focuses on our understanding of iRhoms and the involved mechanisms in the cellular processes. PMID- 26869526 TI - Changes of immunogenic profiles between a single dose and one booster influenza vaccination in hemodialysis patients - an 18-week, open-label trial. AB - Annual influenza vaccination is recommended, but its efficacy in dialysis population is still controversial. Here we aimed to compare the dynamic changes of immune response between various influenza vaccination protocols in hemodialysis patients. A 18-week open label, non-randomized, controlled trial was conducted during 2011-2012. The efficacy between unvaccinated, one- and two-dose regimens were evaluated in 175 hemodialysis patients. Immunogenic profiles were assessed by hemagglutination-inhibition assays. At 3-9 weeks post-vaccination, antibody responses were similar between the one- and two-dose regimens, while the seroprotection rates (antibody titer >=1:40) for influenza A were 55.6-82.5% in the adult (18-60 years) and 33.3-66.7% in the elderly (>60 years). Meanwhile, the seroprotection rates for influenza B were low (4.0-25.0%). By 18 weeks post vaccination, the seroprotection rates for influenza A and B declined (0.0-33.3%) in both the adult and elderly receiving one- or two-dose regimens. Of dialysis patients, at most 2.4% developed moderate to severe adverse effects(myalgia and headache) after vaccination. In conclusion, the two-dose regimen could not improve immune responses than the one-dose regimen in hemodialysis patients; meanwhile the induced protective antibodies of both regimens could not be maintained for more than 4 months. Modification of current influenza vaccination strategy in dialysis population should be re-considered. PMID- 26869527 TI - The cognitive reserve theory in the setting of pediatric-onset multiple sclerosis. AB - BACKGROUND: The study of cognitive reserve (CR) in relationship with cognitive impairment (CI) in pediatric-onset multiple sclerosis (POMS) may provide cues to identifying subjects at higher risk of impairment and scope for therapeutic strategies. OBJECTIVES: To assess the potential impact of CR on cognition in a cohort of POMS patients. METHODS: In all, 48 POMS patients were followed up for 4.7 +/- 0.4 years. CI was defined as the failure of ?3 tests on an extensive neuropsychological battery. Change of neuropsychological performance was assessed through the Reliable Change Index (RCI) method. At baseline, CR was estimated by measuring the intelligence quotient (IQ). The relationships were assessed through multivariable regression analyses. RESULTS: At baseline, CI was detected in 14/48 (29.2%) patients. Two out of 57 healthy control (HC; 3.5%) met the same criteria of CI (p < 0.001). A deteriorating cognitive performance using the RCI method was observed in 18/48 patients (37.6%). Among the 34 cases who were cognitively preserved at baseline, a higher reserve predicted stable/improving performance (odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.03-1.20; p = 0.006). CONCLUSION: Our results suggest that higher CR in POMS patients may protect from CI, particularly in subjects with initial cognitive preservation, providing relevant implications for counseling and rehabilitation strategies. PMID- 26869528 TI - False positivity of anti aquaporin-4 antibodies in natalizumab-treated patients. AB - BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) represent a differential diagnosis of multiple sclerosis (MS). Detection of anti-aquaporin-4 antibodies (AQP4-Ab) is the strongest argument to confirm NMOSD. Diagnosing NMOSD is a major concern because specific MS disease modifying drugs can lead to neurological worsening. OBJECTIVE: To report the case of two natalizumab (NTZ) treated patients who presented a false positive result for AQP4-Ab. METHODS: A retrospective analysis of NTZ-treated patients who were tested positive for AQP4 Ab in our MS center. RESULTS: Two patients treated by NTZ presented a false positive result. CONCLUSIONS: Clinicians should be aware of potential technical issues in detecting AQP4-Ab in NTZ-treated patients leading to false positive results. PMID- 26869529 TI - Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case. AB - BACKGROUND: Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies. OBJECTIVE: To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS. METHODS: Thirty-nine serum samples from patients with MS who had undergone brain biopsy (n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients (n = 15) were tested for anti-MOG, anti-M1-AQP4, anti M23-AQP4, anti-NMDAR, anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABABR), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5 trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase-related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2). RESULTS: Antibodies to MOG belonging to the complement activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown. CONCLUSION: This is the largest study on established anti-neural antibodies performed in MS so far. MOG IgG may play a role in a small percentage of patients diagnosed with pattern II MS. PMID- 26869530 TI - Children with multiphasic disseminated encephalomyelitis and antibodies to the myelin oligodendrocyte glycoprotein (MOG): Extending the spectrum of MOG antibody positive diseases. AB - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibodies have been described in children with acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, neuromyelitis optica spectrum disorders and more recently in children with multiphasic disseminated encephalomyelitis (MDEM). OBJECTIVE: To delineate the clinical, cerebrospinal fluid (CSF) and radiological features of paediatric MDEM with MOG antibodies. METHODS: Clinical course, serum antibodies, CSF, magnetic resonance imaging (MRI) studies and outcome of paediatric MDEM patients were reviewed. RESULTS: A total of 8 children with two or more episodes of ADEM were identified from a cohort of 295 children with acute demyelinating events. All children had persisting MOG antibodies (median titre: 1:1280). All ADEM episodes included encephalopathy, polyfocal neurological signs and a typical MRI. Apart from ADEM episodes, three children had further clinical attacks without encephalopathy. Median age at initial presentation was 3 years (range: 1 7 years) and median follow-up 4 years (range: 1-8 years). New ADEM episodes were associated with new neurological signs and new MRI lesions. Clinical outcome did range from normal (four of the eight) to mild or moderate impairment (four of the eight). A total of four children received monthly immunoglobulin treatment during the disease course. CONCLUSION: Children with MDEM and persisting MOG antibodies constitute a distinct entity of relapsing demyelinating events and extend the spectrum of MOG antibody-associated diseases. PMID- 26869531 TI - The relationship of age with the clinical phenotype in multiple sclerosis. AB - BACKGROUND: The multiple sclerosis (MS) clinical course and relapses frequency before progression vary widely. OBJECTIVE: To investigate the influence of age on the MS phenotype. METHODS: Among 751 primary progressive (PP = 217) and secondary progressive (SP = 534) MS patients from the London Ontario database, we assessed the relationship of age on the relapse frequency and on the progressive phase evolution, and the impact of relapses on the age at onset of progression. RESULTS: Age at onset did not influence the early attacks frequency, but patients younger at onset had larger number of total attacks before progression (age = 27.4, 31.0 and 32.8 mean years; ?4, 2-3 and 1 relapses, respectively) and longer latency to SP. Although frequent early relapses predicted younger age at SP onset, patients with no attacks (primary progressive multiple sclerosis (PPMS)), or 1, 2-3 and ?4 relapses during the relapsing-remitting phase started progressing at similar age (38.6, 41.3, 41.4 and 39.2 mean years, respectively). The age at onset of progressive phase did not affect its evolution. CONCLUSIONS: Age strongly influences the phenotype before progression. Relapsing-remitting patients younger at onset are more likely to display a predominantly inflammatory course, yet relapses number does not affect the age at onset of progression. PMID- 26869532 TI - Dengue and chikungunya seroprevalence in Gabonese infants prior to major outbreaks in 2007 and 2010: A sero-epidemiological study. AB - BACKGROUND: Apart from outbreak reports, little is known about the endemicity of dengue and chikungunya virus in African countries. We investigated serum samples collected in Gabon before major outbreaks in 2007 and 2010 in order to identify pre-outbreak-circulation of both viruses. METHODS: Serum samples from Gabonese infants (162) were analyzed at 3, 9, 15 and 30 months of age by commercial ELISA for dengue and chikungunya IgG-antibodies. If samples were positive medical records of participants were analyzed for symptoms concordant with dengue and chikungunya infections during the time period of assumed seroconversion. RESULTS: IgG-antibodies against dengue were found in 12.3%, and IgG-antibodies against chikungunya in 0.6% of infants tested. Using the four measuring time points, we estimated corresponding incidences of 51/1.000 person-years and 2.5/1.000 person years, respectively. Symptoms in positive-tested infants were mostly non specific. CONCLUSION: Seropositivity suggests that both viruses circulated before the well-noticed outbreaks. Clinical diagnosis of dengue and chikungunya is difficult especially in infants, underscoring the need for accurate and reliable diagnostic tests as well as awareness of medical personnel. CLINICAL TRIALS REGISTRATION: NCT00167843. PMID- 26869533 TI - Diagnosis of arboviral infections--A quagmire of cross reactions and complexities. PMID- 26869534 TI - Grading of follicular lymphoma in cytological samples. AB - OBJECTIVE: The treatment of follicular lymphoma (FL) depends on its grade. The current World Health Organization (WHO) 2008 Classification of Tumours of Haematopoietic and Lymphoid Tissues recommends the grading of FL on histological samples according to the Mann and Berard method, taking into consideration the number of centroblasts. There is no generally accepted method for the grading of FL in fine needle aspiration biopsy (FNAB) samples. The aim of the present study was to devise a grading system for FL in cytological samples. METHODS: Flow cytometry (FC) was performed on 60 FNAB samples of patients with primary FL. We assumed that FL cells larger than reactive T lymphocytes on FC histograms corresponded to centroblasts. The percentage of large cells was calculated and compared with histological grade, proliferative activity and number of centroblasts per high-power field (HPF) on histological slides, and with survival. RESULTS: The histological analysis of lymph nodes revealed 20 patients with high-grade and 40 patients with low-grade FL. The percentage of large cells in FNAB samples correlated significantly with histological grade (P = 0.02), MIB1 status (P < 0.001) and the number of centroblasts per HPF (P < 0.001). An age over 60 years and a percentage of large cells over 50% in FNAB samples were found to have a statistically significant impact on survival by univariate analysis (P = 0.001 and P = 0.006, respectively). CONCLUSIONS: The percentage of large lymphoma cells in FNAB samples of FL determined by FC can be used as a reliable method for FL grading, as it is comparable with the histological grading system. PMID- 26869535 TI - The effectiveness of e-learning in pediatric medical student education. AB - BACKGROUND: Electronic learning allows individualized education and may improve student performance. This study assessed the impact of e-modules about infection control and congenital infections on medical knowledge. METHODS: A descriptive study was conducted involving third-year medical students on pediatric clerkship. e-Module content in three different formats was developed: a text monograph, a PowerPoint presentation, and a narrated PowerPoint lecture. Students' use of the e-modules was tracked, as was participation in the infectious disease rotation and the order of pediatric rotation. Pre- and posttests specific to the e-module content and National Board of Medical Examiners (NBME) pediatric exam scores were recorded. RESULTS: Among 67 participants, 63% of them visited at least one e module. Neither accessing any e-modules, timing of pediatric clerkship, nor assignment to ID rotation resulted in improved posttest nor NBME scores. Seventy percent of students rated the e-modules as satisfactory and reported usage improved their confidence with the congenital infections topic. DISCUSSION: e Modules did not improve student performance on NBME or posttest; however, they were perceived as satisfactory and to have improved confidence among those who used them. This study underscores the importance of formally evaluating electronic and other innovative curricula when implemented within existing medical education frameworks. PMID- 26869536 TI - Protein function prediction based on data fusion and functional interrelationship. AB - One of the challenging tasks of bioinformatics is to predict more accurate and confident protein functions from genomics and proteomics datasets. Computational approaches use a variety of high throughput experimental data, such as protein protein interaction (PPI), protein sequences and phylogenetic profiles, to predict protein functions. This paper presents a method that uses transductive multi-label learning algorithm by integrating multiple data sources for classification. Multiple proteomics datasets are integrated to make inferences about functions of unknown proteins and use a directed bi-relational graph to assign labels to unannotated proteins. Our method, bi-relational graph based transductive multi-label function annotation (Bi-TMF) uses functional correlation and topological PPI network properties on both the training and testing datasets to predict protein functions through data fusion of the individual kernel result. The main purpose of our proposed method is to enhance the performance of classifier integration for protein function prediction algorithms. Experimental results demonstrate the effectiveness and efficiency of Bi-TMF on multi-sources datasets in yeast, human and mouse benchmarks. Bi-TMF outperforms other recently proposed methods. PMID- 26869537 TI - Domino effect: An unusual case of six fatal hydrogen sulfide poisonings in quick succession. AB - Hydrogen sulfide (H2S) is one of the most serious toxic gases encountered in forensic practice. Aside from being a by-product of many industrial processes, this gas is naturally produced during the putrefaction of organic substances. We report six autopsy cases of fatal H2S poisonings from inhalation of H2S gas after an occupational accident. These six men died during the unblocking of a wastewater cistern. The first worker died shortly after clearing the obstruction, the other five died, one by one, as they attempted to help their colleagues. The macroscopic and histological findings are discussed here to provide useful information for future cases. Greenish discoloration of the skin and of internal organs (liver, trachea, esophagus, stomach) was observed, and one case showed signs typical of drowning. We present a very unusual incident, complete with rare photographs and toxicological analysis. In these cases, based on both macroscopic and microscopic findings, the cause of death was most likely an inhibitory effect on cellular cytochrome oxidase causing respiratory failure. PMID- 26869540 TI - Ectopic pregnancy in an undescended fallopian tube: a diagnostic challenge. AB - Uterine malformations are the most frequent anomalies of the Mullerian ducts, but undescended ovaries and fallopian tubes are very rare congenital defects. Pregnancy in these misplaced organs may occur, frequently posing a diagnostic challenge. A case of a ruptured ectopic pregnancy in an undescended fallopian tube associated with other genital malformations is presented. This case provides evidence for the recognised phenomenon of peritoneal gametes or embryo transmigration. PMID- 26869541 TI - Influence of Eyelid Pressure on Fluorescein Staining of Ocular Surface in Dry Eyes. PMID- 26869542 TI - Documenting the indigenous knowledge on medicinal flora from communities residing near Swat River (Suvastu) and in high mountainous areas in Swat-Pakistan. AB - AIM OF THE STUDY: The present study aimed at documenting the indigenous knowledge on medicinal flora from the local communities residing near Swat River and high mountainous areas in Swat, Pakistan. MATERIALS AND METHODS: Field study was carried out in 2013-14. The area was visited 17 times, and semi-structured and open-ended interviews were conducted in both the plain area nearby the Swat River (4 villages) and mountains (7 villages). A total of 83 erudite informants participated in the interviews with their prior consent. The collected data were analysed through quantitative indices viz., medicinal use value (MUV), relative frequency citation (RFC), family use value (FUV), informant consensus factor (ICF) and fidelity level (FL). RESULTS: A total of 78 species belonging to 45 vascular plant families were documented as medicinally important. Lamiaceae was observed the dominant medicinal plant family with 11 species, leaf was the most used part, and powder the most preferred preparation type. Maximum MUV (1) was shared by 15 species while maximum RFC (0.385) was demonstrated by both Brassica juncea and Lepidium sativum. Smaller families with mostly 1 species showed higher FUV while among the larger families Amaryllidaceae and Papaveraceae showed maximum FUV of 0.89 and 0.87, respectively. Highest FL was shown by Mentha arvensis (70%) against gastrointestinal diseases. Highest ICF was demonstrated by hepatic disorders (0.93). Furthermore, we revealed 108 indigenous herbal medicinal recipes, 6 plants added to the medicinal plant trade list, 1 species (Vincetoxicum arnottianum) reported for the first time as medicinal plant, and several new uses for 49 well known medicinal plants. CONCLUSION: The present survey documents diverse plant species that are utilised by local communities for treating a broad spectrum of disorders. Quantitative indices helped in marking important and most preferred plants. To conclude, we recommend the plants for pharmacological studies, documenting new uses, especially Vincetoxicum arnottianum, never screened before. PMID- 26869543 TI - Isolated flavonoids from Ficus racemosa stem bark possess antidiabetic, hypolipidemic and protective effects in albino Wistar rats. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ficus racemosa (FR) has been used for thousands of years in Ayurvedic system of medicine in India and is closely associated with prevention, treatment and cure of various human ailments like obesity and diabetes. It is popularly known as gular. A vast and wide range of chemical compounds like polyphenols, friedelane-type triterpenes, norfriedelane type triterpene, eudesmane-type sesquiterpene including various glycosides had been isolated from this plant. However, no detail studies related to isolation of flavonoids has been reported previously with their antidiabetic, hypolipidemic and toxicological consequences. AIM OF THE STUDY: The present study was undertaken to evaluate antidiabetic, hypolipidemic and toxicological assessments of flavonoids isolated from Ficus racemosa (FR) stem bark. MATERIALS AND METHODS: We isolated four flavonoids from stem bark of FR and structures were confirmed by Infrared spectroscopy (IR), Nuclear Magnetic Resonance (NMR) (both 1D and 2D), mass spectroscopy (MS). Later, these flavonoids were administered to streptozotocin (STZ) rats once in a day for a period of seven days at 100mg/kg dose. We measured blood glucose level and body weight changes at different days (1st, 3rd, 5th and 7th days). Serum lipid profiles were also estimated to investigate the hypolipidemic potential of flavonoids in the similar experiment. Various oxidative stress parameters in pancreas and liver and hepatic biomarker enzymes in plasma were also determined to investigate the toxicity potential of isolated flavonoids. Finally, we performed docking studies to find out the mechanism of action. RESULTS: Our results collectively suggested that four flavonoids reduced blood glucose level and restored body weight, signifying antidiabetic action. There were reduction of other lipid profile parameters and increase of high density lipoprotein (HDL) during administration of flavonoids, also signifying hypolipidemic action. Various oxidative stress biomarkers and hepatic enzymes levels were also normalized with respect to diabetic control at the same time. Docking studies revealed that isolated flavonoids showed their antidiabetic potential via binding to PPARgamma and GLUT1 receptors. CONCLUSION: The isolated four flavonoids demonstrated good antidiabetic, hypolipidemic and antioxidant properties in STZ diabetic rats which supported the use of FR stem bark as useful supplementary drug for future antidiabetic therapy. PMID- 26869544 TI - Ethnopharmacological survey of plant species used in folk medicine against central nervous system disorders in Togo. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Neurological diseases are rising all around the world. In a developing country such as Togo, although plant-based medicines are the only means, still very little is known regarding the nature and efficiency of medicinal plants used by indigenous people to manage central nervous system (CNS) disorders. AIM OF THE STUDY: This study, an ethnobotanical survey, aimed to report plant species used in traditional medicine (TM) for the management of various CNS disorders in Togo. MATERIALS AND METHODS: 52 traditional actors (TA) including 33 traditional healers (TH) and 19 medicinal plant sellers (MPS) were interviewed, using a questionnaire mentioning informants' general data and uses of medicinal plants. RESULTS: The present study reports 44 medicinal plant species distributed into 26 families, mentioning scientific and common local names, plant organs used, preparation method, root of administration and putative applications. CONCLUSION: It appears that there is a real knowledge on medicinal plants used for traditional treatment of CNS disorders in Togo and that the local flora abounds of potentially neuroactive plants which could be useful for the discovery of antipsychotic or neuroprotective molecules. PMID- 26869545 TI - Traditional Arabic Palestinian ethnoveterinary practices in animal health care: A field survey in the West Bank (Palestine). AB - BACKGROUND: In Palestine, medicinal plants have continued to play a vital role in fulfilling animal healthcare needs of rural communities. However, these valuable resources are being depleted mainly due to over-harvesting, inappropriate agricultural practices (e.g., over use of herbicides), agricultural expansion, and over-grazing. Therefore, immediate action is required to conserve these resources and document the associated knowledge. The purpose of this study was, thus, to document and analyze information associated with medicinal plants that are used in managing animal health problems in the West Bank, Palestine. MATERIALS AND METHODS: Ethnobotanical data were collected from Apr 2012 to Feb 2014 mainly using semi-structured interviews with informants sampled using purposive sampling technique and through field observations. RESULTS: The study revealed the use of 138 medicinal plant species in the West Bank for the treatment of several livestock diseases, of these 75 species representing 70 genera and 33 families were reported by 3 independent informants or above. Classification of the ethnoveterinary plant species cited by three informants or above used in a rank-order priority (ROP) based on their claimed relative healing potential has demonstrated that the following are the plants with the highest efficacy: Camellia sinenses, Teucrium capitatum, and Salvia fruticosa with ROPs of 97.1, 93.2, and 91.4, respectively, are used primarily to relieve gastric disorders. Gastrointestinal disorders is the disease group in the study area that scored the highest Informant consensus factor (ICF) value (0.90), followed by urinary, and reproductive disorders (0.89). CONCLUSION: Our study provided evidence that medicinal plants are still playing important role in the management of livestock diseases, and showed that ethnoveterinary plants used in animal health care in Palestine have been also recorded in human Traditional Arabic Palestinian Herbal Medicine (TAPHM), and demonstrated a strong link between human and veterinary medical practices. This survey has identified a number of important medicinal plants used by the Palestinian farmers of the West Bank area for the treatment of various animal ailments. It provides a baseline for future phytochemical and pharmacological investigations into the beneficial medicinal properties of such plants. PMID- 26869546 TI - Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging. AB - Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG ((111)In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5-40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method ((111)In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using (111)In-DTPA PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging. PMID- 26869547 TI - Reciprocal Effects of Life Satisfaction and Depressive Symptoms Within Long-Wed Couples Over Time. AB - Objectives: This study was undertaken to examine bidirectional effects of well being over time in long-wed couples. Method: We recruited 125 couples 50+ years of age who had been married 20+ years. Both spouses reported life satisfaction and depressive symptoms independently at three annual points over 2 years. We computed actor-partner interdependence models (APIMs) to identify concomitant and longitudinal bidirectional effects between long-wed spouses. Where parallel associations were found between models of life satisfaction and depressive symptoms, we undertook invariance analyses to compare the relative strength of associations. Results: We observed a significant association between wives' and their husbands' life satisfaction at baseline; a concomitant crossover effect was also evident from wives to husbands at 1- and 2-year follow-up, such that wives' life satisfaction predicted changes in their husbands' life satisfaction beyond that previously and concomitantly reported. Discussion: Our findings suggest that older wives influence their husbands after decades of marriage; the relative effect of this crossover on older husbands is comparatively equivalent for life satisfaction and depressive symptoms. These findings stand in contrast to prior research with younger couples suggesting that long-wed couples may be a distinct subset of the population of all married couples (i.e., those who have not divorced). PMID- 26869548 TI - Ebola's legacy: UK deficits and their global lessons. PMID- 26869549 TI - Breastfeeding: achieving the new normal. PMID- 26869550 TI - US drug overdose deaths: a global challenge. PMID- 26869551 TI - Modest global achievements in maternal survival: more focus on sub-Saharan Africa is needed. PMID- 26869553 TI - Breastfeeding: a smart investment in people and in economies. PMID- 26869552 TI - Spotlight on infant formula: coordinated global action needed. PMID- 26869554 TI - Retraction--Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. PMID- 26869556 TI - Australia commits funds to curb hepatitis C epidemic. PMID- 26869557 TI - HIV in Mozambique: starting, and staying on, treatment. PMID- 26869558 TI - Profile: Boston University School of Public Health at 40. PMID- 26869560 TI - Charlotte Watts: from pure maths to HIV and gender-based violence. PMID- 26869561 TI - The body politic. PMID- 26869562 TI - Robert L Spitzer. PMID- 26869563 TI - Faith-based health care. PMID- 26869564 TI - Faith-based health care. PMID- 26869565 TI - Faith-based health care. PMID- 26869566 TI - Climate change and health. PMID- 26869567 TI - Climate change and health. PMID- 26869568 TI - Climate change and health. PMID- 26869569 TI - Climate change and health. PMID- 26869570 TI - Prophylactic antibiotics to reduce pneumonia after acute stroke. PMID- 26869571 TI - Prophylactic antibiotics to reduce pneumonia after acute stroke. PMID- 26869572 TI - The promise of personalised medicine. PMID- 26869573 TI - Prophylactic antibiotics to reduce pneumonia after acute stroke - Author's reply. PMID- 26869574 TI - Frailty in emergency departments. PMID- 26869575 TI - Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. AB - The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries. In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor. Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes. The scaling up of breastfeeding to a near universal level could prevent 823,000 annual deaths in children younger than 5 years and 20,000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor. PMID- 26869577 TI - Heteroatom-Containing Porous Carbons Derived from Ionic Liquid-Doped Alkali Organic Salts for Supercapacitors. AB - A simple strategy for the synthesis of heteroatom-doped porous carbon materials (CMs) via using ionic liquid (IL)-doped alkali organic salts as small molecular precursors is developed. Doping of alkali organic salts (such as sodium glutamate, sodium tartrate, and sodium citrate) with heteroatoms containing ILs (including 1-butyl-3-methylimidazolium chlorine and 3-butyl-4 methythiazolebromination) not only incorporates the heteroatoms into the carbon frameworks but also highly improves the carbonization yield, as compared with that of either alkali organic salts or ILs as precursors. The porous structure of CMs can be tuned by adjusting the feed ratio of ILs. The porous CMs derived from 1-butyl-3-methylimidazolium chlorine-doped sodium glutamate exhibit high charge storage capacity with a specific capacitance of 287 F g(-1) and good stability over 5000 cycles in 6 m KOH at a current density of 1 A g(-1) for supercapacitors. This strategy opens a simple and efficient method for the synthesis of heteroatom-doped porous CMs. PMID- 26869576 TI - Why invest, and what it will take to improve breastfeeding practices? AB - Despite its established benefits, breastfeeding is no longer a norm in many communities. Multifactorial determinants of breastfeeding need supportive measures at many levels, from legal and policy directives to social attitudes and values, women's work and employment conditions, and health-care services to enable women to breastfeed. When relevant interventions are delivered adequately, breastfeeding practices are responsive and can improve rapidly. The best outcomes are achieved when interventions are implemented concurrently through several channels. The marketing of breastmilk substitutes negatively affects breastfeeding: global sales in 2014 of US$44.8 billion show the industry's large, competitive claim on infant feeding. Not breastfeeding is associated with lower intelligence and economic losses of about $302 billion annually or 0.49% of world gross national income. Breastfeeding provides short-term and long-term health and economic and environmental advantages to children, women, and society. To realise these gains, political support and financial investment are needed to protect, promote, and support breastfeeding. PMID- 26869578 TI - Voluntary pulmonary function screening identifies high rates of undiagnosed asymptomatic chronic obstructive pulmonary disease. AB - Chronic obstructive pulmonary disease (COPD) is projected to be the third leading cause of death by 2020. Early detection and screening may alter the course and prognosis associated with lung disease. We investigated the effectiveness of a voluntary public lung function screening program and factors that had a predictive value for asymptomatic COPD in Xi'an, China. Pulmonary function testing (PFT) was conducted on volunteers recruited from four community centers in Xi'an, China, between July and August 2012. Participants underwent three forced vital capacity maneuvers. The maneuver with the best forced expiratory volume in first second was retained. Participants filled out a medical history and environmental exposure survey before undergoing the PFT. Patients who self reported lung disease on the health survey were excluded from the analysis. Logistical regression was used to determine associations with airway obstruction. A total of 803 volunteers participated in this study, and 33 subjects were excluded as the participants did not meet the requirements of PFT. Of the 770 volunteers, 44 participants had been diagnosed with chronic respiratory diseases previously, and 144 participants (18.7%) met COPD criteria. Four hundred forty four participants did not self-report any respiratory symptoms, and the remaining 282 participants self-reported respiratory symptoms. Of the asymptomatic participants, 98 volunteers had PFT results that were consistent with COPD and 68.1% of asymptomatic participants were undiagnosed. A greater percentage of women than men had moderate or severe airway obstruction (p = 0.004).Only smoking status (odds ratio = 2.64, 95% confidence interval 1.20-6.04) was associated with asymptomatic COPD. Voluntary public lung function screening programs in China are likely to identify a large number of undiagnosed, asymptomatic COPD. Smoking status is associated with airway obstruction and a greater percentage of women than men had moderate or severe airway obstruction. PMID- 26869580 TI - Fall in 1:1 nursing ratios in neonatal ICUs is linked to higher death rate. PMID- 26869579 TI - Comparison of the six-minute walk test with a cycle-based cardiopulmonary exercise test in people following curative intent treatment for non-small cell lung cancer. AB - This study is aimed to (i) compare both the magnitude of impairment in exercise capacity and exercise responses measured during the six-minute walk test (6MWT) and the cardiopulmonary exercise test (CPET) and (ii) investigate the effect of test repetition on six-minute walk distance (6MWD) in people following curative intent treatment for non-small cell lung cancer (NSCLC). Twenty participants (67 +/- 10 years; 14 females), 6-10 weeks following lobectomy, underwent a CPET and two 6MWTs. Peak exercise responses, dyspnoea and leg fatigue, as well as heart rate (HR) and oxygen saturation (SpO2) during the 6MWT, were compared to those during the CPET. Compared with exercise capacity when expressed as peak rate of oxygen consumption (%pred) measured during the CPET, exercise capacity when expressed as 6MWD (%pred) was less impaired (81 +/- 10 vs. 63 +/- 15 %pred; p < 0.001). Compared with the CPET, the 6MWT elicited lower peak HR (119 +/- 15 vs. 128 +/- 18 beats minute(-1); p = 0.02), lower SpO2 (93 +/- 2 vs. 95 +/- 3%; p < 0.05), less dyspnoea (3.1 +/- 1.6 vs. 6.9 +/- 2.6; p < 0.01) and less leg fatigue (2.0 +/- 1.9 vs. 6.8 +/- 2.4; p < 0.01). The 6MWD increased 19 +/- 19 metre (4 +/ 4%) with test repetition (p < 0.001). In people following curative intent treatment for NSCLC, the 6MWT appears to elicit sub-maximal exercise responses when compared with the CPET. There is a significant effect of test repetition on 6MWD. PMID- 26869581 TI - High-flow nasal cannula: Mechanisms, evidence and recommendations. AB - The use of high-flow nasal cannula (HF) therapy as respiratory support for preterm infants is rapidly increasing, due to its perceived ease of use and other potential benefits over the standard 'non-invasive' respiratory support, continuous positive airway pressure (CPAP). The evidence from randomized trials suggests that HF is an alternative to CPAP for post-extubation support of preterm infants. Limited data are available from randomized trials comparing HF with CPAP as primary support, and few trials have included extremely preterm infants. This review discusses the proposed mechanisms of action of HF, the evidence from clinical trials of HF use in preterm infants, and proposes recommendations for evidence-based practice. PMID- 26869582 TI - The crystal structure of human GlnRS provides basis for the development of neurological disorders. AB - Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggest that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. This report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. PMID- 26869584 TI - Association of Macroeconomic Factors With Nonrelapse Mortality After Allogeneic Hematopoietic Cell Transplantation for Adults With Acute Lymphoblastic Leukemia: An Analysis From the Acute Leukemia Working Party of the EBMT. AB - PURPOSE: From a global perspective, the rates of allogeneic hematopoietic cell transplantation (alloHCT) are closely related to the economic status of a country. However, a potential association with outcome has not yet been documented. The goal of this study was to evaluate effects of health care expenditure (HCE), Human Development Index (HDI), team density, and center experience on nonrelapse mortality (NRM) after HLA-matched sibling alloHCT for adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 983 patients treated with myeloablative alloHCT between 2004 and 2008 in 24 European countries were included. RESULTS: In a univariate analysis, the probability of day 100 NRM was increased for countries with lower current HCE (8% vs. 3%; p = .06), countries with lower HDI (8% vs. 3%; p = .02), and centers with less experience (8% vs. 5%; p = .04). In addition, the overall NRM was increased for countries with lower current HCE (21% vs. 17%; p = .09) and HDI (21% vs. 16%; p = .03) and for centers with lower activity (21% vs. 16%; p = .07). In a multivariate analysis, the strongest predictive model for day 100 NRM included current HCE greater than the median (hazard ratio [HR], 0.39; p = .002). The overall NRM was mostly predicted by HDI greater than the median (HR, 0.65; p = .01). Both lower current HCE and HDI were associated with decreased probability of overall survival. CONCLUSION: Both macroeconomic factors and the socioeconomic status of a country strongly influence NRM after alloHCT for adults with ALL. Our findings should be considered when clinical studies in the field of alloHCT are interpreted. PMID- 26869583 TI - Discovering hotspots in functional genomic data superposed on 3D chromatin configuration reconstructions. AB - The spatial organization of the genome influences cellular function, notably gene regulation. Recent studies have assessed the three-dimensional (3D) co localization of functional annotations (e.g. centromeres, long terminal repeats) using 3D genome reconstructions from Hi-C (genome-wide chromosome conformation capture) data; however, corresponding assessments for continuous functional genomic data (e.g. chromatin immunoprecipitation-sequencing (ChIP-seq) peak height) are lacking. Here, we demonstrate that applying bump hunting via the patient rule induction method (PRIM) to ChIP-seq data superposed on a Saccharomyces cerevisiae 3D genome reconstruction can discover 'functional 3D hotspots', regions in 3-space for which the mean ChIP-seq peak height is significantly elevated. For the transcription factor Swi6, the top hotspot by P value contains MSB2 and ERG11 - known Swi6 target genes on different chromosomes. We verify this finding in a number of ways. First, this top hotspot is relatively stable under PRIM across parameter settings. Second, this hotspot is among the top hotspots by mean outcome identified by an alternative algorithm, k-Nearest Neighbor (k-NN) regression. Third, the distance between MSB2 and ERG11 is smaller than expected (by resampling) in two other 3D reconstructions generated via different normalization and reconstruction algorithms. This analytic approach can discover functional 3D hotspots and potentially reveal novel regulatory interactions. PMID- 26869585 TI - While We're at It, Let's Whack the FDA. PMID- 26869586 TI - Daily reduction of oral malodor with the use of a sonic tongue brush combined with an antibacterial tongue spray in a randomized cross-over clinical investigation. AB - The objective of this clinical investigation was to test the effectiveness on breath odor of a newly designed sonic tongue brush (TongueCare+, TC). It consists of a soft silicone brush optimally designed based on the tongue's anatomy to remove bacterial biofilm from the tongue's complex surface, and it is coupled with a sonic power toothbrush handle. TC was used in combination with an antibacterial tongue spray (BreathRx, BRx) containing 0.09% cetylpyridinium chloride and 0.7% zinc gluconate. A total of 21 participants with oral malodor exceeding the threshold for recognition took part in this cross-over clinical investigation, which consisted of a single use of four treatment arms with one week washout period in between. The treatments consisted of: (1) TC + BRx, (2) TC + water, (3) BRx and (4) water. Malodor levels and bacterial density were monitored up to 6 h by organoleptic scoring and selective plating, respectively. The organoleptic score and bacterial density were significantly lower after using TC + BRx compared to all alternative treatments at all time points. A significant decrease in both parameters was detected after a single use of TC + BRx, from levels characteristic of high oral malodor, to barely noticeable levels after treatment and this was maintained up to 6 h. Moreover, we identified a significant positive correlation between bacterial density and organoleptic score, confirming that bacterial tongue biofilm is the root cause of oral malodor in these subjects. The results of this clinical investigation demonstrated that the combined treatment of a sonic tongue brush with the antibacterial tongue spray is able to deliver more than 6 h of fresh breath following a single use. The clinical investigation was registered at the ISRCTN registry under study identification number ISRCTN38199132. PMID- 26869587 TI - Junior contract will be imposed, Hunt announces. PMID- 26869588 TI - The benefit of surgical resection in recurrent glioblastoma. PMID- 26869589 TI - The validity of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis. AB - BACKGROUND: A range of questionnaires have been used to assess health-related quality of life (HRQOL) in bronchiectasis. A systematic review was conducted to evaluate their psychometric properties and assess associations between HRQOL and clinical measures. METHODS: Five electronic databases were searched. Studies eligible for inclusion were those that investigated the validity of HRQOL questionnaires and/or their association with other outcomes in adults with bronchiectasis. Patients with cystic fibrosis were excluded. The identified questionnaires were assessed for convergent, discriminant and cross-cultural translation validity; missing data, floor and ceiling effects, internal consistency, responsiveness and test-retest reliability. A meta-analysis was conducted to estimate the strength of associations between HRQOL and clinical measures. RESULTS: From 1918 studies identified, 43 studies were included in the systematic review, of which 38 were suitable for the meta-analysis. Nine HRQOL questionnaires were identified, with the most widely used being: St George's Respiratory Questionnaire, Leicester Cough Questionnaire, Quality of Life Bronchiectasis and Short Form-36. HRQOL questionnaires had moderate to good internal consistency and good test-retest reliability. Only 8 of 18 studies that used translated HRQOL questionnaires reported or referred to the validity of the translated questionnaire. There was a stronger correlation (mean r (95% CI)) between HRQOL and subjective outcome measures, such as dyspnoea (0.55 (0.41 to 0.68)) and fatigue (0.42 (0.23 to 0.58)) compared with objective measures; exercise capacity (-0.41 (-0.54 to -0.24)), FEV1% predicted (-0.31 (-0.40 to 0.23)) and extent of bronchiectasis on CT scan (0.35 (0.03 to 0.61)); all p<0.001. CONCLUSIONS: This review supports most HRQOL questionnaires used in bronchiectasis have good psychometric properties. There was a weak to moderate association between HRQOL and objective outcome measures. This suggests that HRQOL questionnaires assess a unique aspect of health not captured by objective measures. PMID- 26869595 TI - Play-based interventions improve physical function for people with adult-acquired brain injury: a systematic review and meta-analysis of randomised controlled trials. AB - OBJECTIVE: To undertake a systematic review and meta-analysis of the effectiveness of play-based interventions compared to traditional therapy in rehabilitation of adults with adult-acquired brain injury. DATA SOURCES: The search was performed using Medline; Cinahl Plus; Health Source (Nursing/Academic Edition); Psychology and behavioural sciences collection; Biomedical reference collection (basic). REVIEW METHODS: Studies included were randomised controlled trials that investigated the effect of play-based interventions on physical function of adults with adult acquired brain injury. Two independent reviewers identified eligible studies and assessed methodological quality using a modified Downs and Black. Meta-analysis compared standardised differences in means, to determine effect sizes for grouped functional outcome measures. The GRADE scoring system was used to determine the level of clinical evidence. RESULTS: Thirty studies met the inclusion criteria, 13 were considered high quality and 17 moderate quality. Studies predominantly involved post-stroke participants, with only three studies including participants with traumatic brain injury. When compared to traditional therapy, dose-matched studies of play-based interventions showed a significant effect on independence (Effect size (ES) = 0.6) and physical performance (ES = 0.43), as measured using the Fugl -Meyer. For non-dose matched studies, play-based interventions showed a significant improvement for balance (ES = 0.76) compared with traditional therapy. In all studies that measured participant enjoyment, play-based therapy was rated as more enjoyable than traditional therapy. CONCLUSION: Play-based interventions for people with adult acquired brain injury are more effective in improving balance and independence, which may be due to them being more enjoyable than traditional therapy. PMID- 26869596 TI - Effects of training with a passive hand orthosis and games at home in chronic stroke: a pilot randomised controlled trial. AB - OBJECTIVES: To compare user acceptance and arm and hand function changes after technology-supported training at home with conventional exercises in chronic stroke. Secondly, to investigate the relation between training duration and clinical changes. DESIGN: A randomised controlled trial. SETTING: Training at home, evaluation at research institute. SUBJECTS: Twenty chronic stroke patients with severely to mildly impaired arm and hand function. INTERVENTIONS: Participants were randomly assigned to six weeks (30 minutes per day, six days a week) of self-administered home-based arm and hand training using either a passive dynamic wrist and hand orthosis combined with computerised gaming exercises (experimental group) or prescribed conventional exercises from an exercise book (control group). MAIN MEASURES: Main outcome measures are the training duration for user acceptance and the Action Research Arm Test for arm and hand function. Secondary outcomes are the Intrinsic Motivation Inventory, Fugl-Meyer assessment, Motor Activity Log, Stroke Impact Scale and grip strength. RESULTS: The control group reported a higher training duration (189 versus 118 minutes per week, P = 0.025). Perceived motivation was positive and equal between groups ( P = 0.935). No differences in clinical outcomes over training between groups were found (P ? 0.165). Changes in Box and Block Test correlated positively with training duration ( P = 0.001). CONCLUSIONS: Both interventions were accepted. An additional benefit of technology-supported arm and hand training over conventional arm and hand exercises at home was not demonstrated. Training duration in itself is a major contributor to arm and hand function improvements. PMID- 26869597 TI - Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. AB - OBJECTIVES: To investigate the risks of invasive cervical cancer after detection of atypical glandular cells (AGC) during cervical screening. DESIGN: Nationwide population based cohort study. SETTING: Cancer and population registries in Sweden. PARTICIPANTS: 3,054,328 women living in Sweden at any time between 1 January 1980 and 1 July 2011 who had any record of cervical cytological testing at ages 23-59. Of these, 2,899,968 women had normal cytology results at the first screening record. The first recorded abnormal result was atypical glandular cells (AGC) in 14 625, high grade squamous intraepithelial lesion (HSIL) in 65 633, and low grade squamous intraepithelial lesions (LSIL) in 244 168. MAIN OUTCOME MEASURES: Cumulative incidence of invasive cervical cancer over 15.5 years; proportion of invasive cervical cancer within six months of abnormality (prevalence); crude incidence rates for invasive cervical cancer over 0.5-15.5 years of follow-up; incidence rate ratios compared with women with normal cytology, estimated with Poisson regression adjusted for age and stratified by histopathology of cancer; distribution of clinical assessment within six months after the abnormality. RESULTS: The prevalence of cervical cancer was 1.4% for women with AGC, which was lower than for women with HSIL (2.5%) but higher than for women with LSIL (0.2%); adenocarcinoma accounted for 73.2% of the prevalent cases associated with AGC. The incidence rate of invasive cervical cancer after AGC was significantly higher than for women with normal results on cytology for up to 15.5 years and higher than HSIL and LSIL for up to 6.5 years. The incidence rate of adenocarcinoma was 61 times higher than for women with normal results on cytology in the first screening round after AGC, and remained nine times higher for up to 15.5 years. Incidence and prevalence of invasive cervical cancer was highest when AGC was found at ages 30-39. Only 54% of women with AGC underwent histology assessment within six months, much less than after HSIL (86%). Among women with histology assessment within six months, the incidence rate of cervical cancer after AGC was significantly higher than that after HSIL for up to 6.5 years. CONCLUSIONS: AGC found at cervical screening is associated with a high and persistent risk of cervical cancer for up to 15 years, particularly for cervical adenocarcinoma and women with AGC at age 30-39. Compared with the reduction in risk of cancer seen after HSIL management, management of AGC seems to have been suboptimal in preventing cervical cancer. Research to optimise management is needed, and a more aggressive assessment strategy is warranted. PMID- 26869599 TI - Covalent Immobilization of Penicillin G Acylase onto Fe3O4@Chitosan Magnetic Nanoparticles. AB - Penicillin G acylase (PGA) was immobilized on magnetic Fe3O4@chitosan nanoparticles through the Schiff base reaction. The immobilization conditions were optimized as follows: enzyme/support 8.8 mg/g, pH 6.0, time 40 min, and temperature 25 degrees C. Under these conditions, a high immobilization efficiency of 75% and a protein loading of 6.2 mg/g-support were obtained. Broader working pH and higher thermostability were achieved by the immobilization. In addition, the immobilized PGA retained 75% initial activity after ten cycles. Kinetic parameters Vmax and Km of the free and immobilized PGAs were determined as 0.91 mmol/min and 0.53 mmol/min, and 0.68 mM and 1.19 mM, respectively. Synthesis of amoxicillin with the immobilized PGA was carried out in 40% ethylene glycol at 25 degrees C and a conversion of 72% was obtained. These results showed that the immobilization of PGA onto magnetic chitosan nanoparticles is an efficient and simple way for preparation of stable PGA. PMID- 26869598 TI - Secondhand smoke exposure at home among one billion children in 21 countries: findings from the Global Adult Tobacco Survey (GATS). AB - OBJECTIVE: Children are vulnerable to secondhand smoke (SHS) exposure because of limited control over their indoor environment. Homes remain the major place where children may be exposed to SHS. Our study examines the magnitude, patterns and determinants of SHS exposure in the home among children in 21 countries (19 low income and middle-income countries and 2 high-income countries). METHODS: Global Adult Tobacco Survey (GATS) data, a household survey of people 15 years of age or older. Data collected during 2009-2013 were analysed to estimate the proportion of children exposed to SHS in the home. GATS estimates and 2012 United Nations population projections for 2015 were also used to estimate the number of children exposed to SHS in the home. RESULTS: The proportion of children younger than 15 years of age exposed to SHS in the home ranged from 4.5% (Panama) to 79.0% (Indonesia). Of the approximately one billion children younger than 15 years of age living in the 21 countries under study, an estimated 507.74 million were exposed to SHS in the home. China, India, Bangladesh, Indonesia and the Philippines accounted for almost 84.6% of the children exposed to SHS. The prevalence of SHS exposure was higher in countries with higher adult smoking rates and was also higher in rural areas than in urban areas, in most countries. CONCLUSIONS: A large number of children were exposed to SHS in the home. Encouraging of voluntary smoke-free rules in homes and cessation in adults has the potential to reduce SHS exposure among children and prevent SHS-related diseases and deaths. PMID- 26869600 TI - Microbial Community Composition in the Marine Sediments of Jeju Island: Next Generation Sequencing Surveys. AB - Marine sediments are a microbial biosphere with an unknown physiology, and the sediments harbor numerous distinct phylogenetic lineages of Bacteria and Archaea that are at present uncultured. In this study, the structure of the archaeal and bacterial communities was investigated in the surface and subsurface sediments of Jeju Island using a next-generation sequencing method. The microbial communities in the surface sediments were distinct from those in the subsurface sediments; the relative abundance of sequences for Thaumarchaeota, Actinobacteria, Bacteroides, Alphaproteobacteria, and Gammaproteobacteria were higher in the surface than subsurface sediments, whereas the sequences for Euryarchaeota, Acidobacteria, Firmicutes, and Deltaproteobacteria were relatively more abundant in the subsurface than surface sediments. This study presents detailed characterization of the spatial distribution of benthic microbial communities of Jeju Island and provides fundamental information on the potential interactions mediated by microorganisms with the different biogeochemical cycles in coastal sediments. PMID- 26869601 TI - Effects of the Antibiotics Growth Promoter Tylosin on Swine Gut Microbiota. AB - Tylosin has been used as a livestock feed additive and antibiotic growth promoter for many years. However, the mode of action by which tylosin enhances animal growth is unclear. We used high-throughput sequencing of 16S rRNA genes to investigate the effects of tylosin as a feed additive on swine gut microbiota. No significant difference in the rate of weight increase was observed between control and tylosin-treated pigs during a 10-week feeding trial. However, tylosin treated pigs showed rapid increases in the relative abundance of the phylum Firmicutes. Increases in Firmicutes species are associated with (so-called) obese type gut microbiota. The abundance of species of four families of the phylum Firmicutes (Streptococcaceae, Peptococcaceae, Peptostreptococcaceae, and Clostridiaceae) correlated positively with host weight gain. The abundance of Streptococcaceae family bacteria was least affected by tylosin treatment. Distribution analysis of operational taxonomic units (OTUs) showed that both control and tylosin-treated pigs exhibited similar OTU alterations during growth. However, the tylosin-treated group showed distinctive alterations in gut microbiota when the host weighed approximately 60 kg, whereas similar alterations occurred at around 80 kg in the control group. Our results suggest that use of tylosin accelerates maturation of swine gut microbiota rather than altering its composition. PMID- 26869602 TI - Duration-Related Variations in Archaeal Communities after a Change from Upland Fields to Paddy Fields. AB - Archaea substantially contribute to global geochemical cycling and energy cycling and are impacted by land-use change. However, the response of archaeal communities to a change from upland field to paddy field has been poorly characterized. Here, soil samples were collected at two depths (0-20 cm and 20-40 cm) from one upland field and six paddy fields that were established on former upland fields at different times (1, 5, 10, 20, 30, and 40 years before the study). Barcoded pyrosequencing was employed to assess the archaeal communities from the samples at taxonomic resolutions from phylum to genus levels. The total archaeal operational taxonomic unit (OTU) richness showed a significant positive correlation with the land-use change duration. Two phyla, Euryarchaeota and Crenarchaeota, were recorded throughout the study. Both the relative abundance and OTU richness of Euryarchaeota increased at both depths but increased more steadily at the subsurface rather than at the surface. However, these data of Crenarchaeota were the opposite. Additionally, the archaeal composition exhibited a significant relationship with C/N ratios, total phosphorus, soil pH, Olsen phosphorus, and the land-use change duration at several taxonomic resolutions. Our results emphasize that after a change from upland fields to paddy fields, the archaeal diversity and composition changed, and the duration is an important factor in addition to the soil chemical properties. PMID- 26869603 TI - Increasing the Triacylglycerol Content in Dunaliella tertiolecta through Isolation of Starch-Deficient Mutants. AB - The production cost of biodiesel from microalgae is still not competitive, compared with that of petroleum fuels. The genetic improvement of microalgal strains to increase triacylglycerol (TAG) accumulation is one way to reduce production costs. One of the most promising approaches is the isolation of starch deficient mutants, which have been reported to successfully increase TAG yields. To date, such a stable mutant is not available in an oleaginous marine microalga, despite several advantages of using marine species for biodiesel production. Algae in the genus Dunaliella are known to tolerate high salt concentration and other environmental stresses. In addition, the cultivation processes for large scale outdoor commercialization have been well established for this genus. In this study, Dunaliella tertiolecta was used to screen for starch-deficient mutants, using an iodine vapor-staining method. Four out of 20,016 UV-mutagenized strains showed a substantial reduction of starch content. A significantly higher TAG content, up to 3-fold of the wild-type level, was observed in three of the mutants upon induction by nitrogen depletion. The carotenoid production and growth characteristics of these mutants, under both normal and oxidative stress conditions, were not compromised, suggesting that these processes are not necessarily affected by starch deficiency. The results from this work open up new possibilities for exploring Dunaliella for biodiesel production. PMID- 26869604 TI - Screening Rice Cultivars for Resistance to Bacterial Leaf Blight. AB - Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious threats to rice production. In this study, screening of rice for resistance to BLB was carried out at two different times and locations; that is, in a greenhouse during winter and in an open field during summer. The pathogenicity of Xoo race K1 was tested on 32 Korean rice cultivars. Inoculation was conducted at the maximum tillering stage, and the lesion length was measured after 14 days of inoculation. Five cultivars, Hanareum, Namcheon, Samgdeok, Samgang, and Yangjo, were found to be resistant in both the greenhouse and open field screenings. Expression of the plant defense-related genes JAmyb, OsNPR1, OsPR1a, OsWRKY45, and OsPR10b was observed in resistant and susceptible cultivars by qRT-PCR. Among the five genes tested, only OsPR10b showed coherent expression with the phenotypes. Screening of resistance to Xoo in rice was more accurate when conducted in open fields in the summer cultivation period than in greenhouses in winter. The expression of plant defenserelated genes after bacterial inoculation could give another perspective in elucidating defense mechanisms by using both resistant and susceptible individuals. PMID- 26869605 TI - The Photoheterotrophic Growth of Bacteriochlorophyll Synthase-Deficient Mutant of Rhodobacter sphaeroides Is Restored by I44F Mutant Chlorophyll Synthase of Synechocystis sp. PCC 6803. AB - Chlorophyll synthase (ChlG) and bacteriochlorophyll synthase (BchG) have a high degree of substrate specificity. The BchG mutant of Rhodobacter sphaeroides, BG1 strain, is photosynthetically incompetent. When BG1 harboring chlG of Synechocystis sp. PCC 6803 was cultured photoheterotrophically, colonies arose at a frequency of approximately 10(-8). All the suppressor mutants were determined to have the same mutational change, ChlGI44F. The mutated enzyme ChlGI44F showed BchG activity. Remarkably, BchGF28I, which has the substitution of F at the corresponding 28(th) residue to I, showed ChlG activity. The Km values of ChlGI44F and BchGF28I for their original substrates, chlorophyllide (Chlide) a and bacteriochlorophyllide (Bchlide) a, respectively, were not affected by the mutations, but the Km values of ChlGI44F and BchGF28I for the new substrates Bchlide a and Chlide a, respectively, were more than 10-fold larger than those for their original substrates, suggesting the lower affinities for new substrates. Taken together, I44 and F28 are important for the substrate specificities of ChlG and BchG, respectively. The BchG activity of ChlGI44F and the ChlG activity of BchGF28I further suggest that ChlG and BchG are evolutionarily related enzymes. PMID- 26869606 TI - Cloning and Characterization of Filamentous Fungal S-Nitrosoglutathione Reductase from Aspergillus nidulans. AB - S-Nitrosoglutathione reductase (GSNOR) metabolizes S-nitrosoglutathione (GSNO) and has been shown to play important roles in regulating cellular signaling and formulating host defense by modulating intracellular nitric oxide levels. The enzyme has been found in bacterial, yeast, mushroom, plant, and mammalian cells. However, to date, there is still no evidence of its occurrence in filamentous fungi. In this study, we cloned and investigated a GSNOR-like enzyme from the filamentous fungus Aspergillus nidulans. The enzyme occurred in native form as a homodimer and exhibited low thermal stability. GSNO was an ideal substrate for the enzyme. The apparent Km and kcat values were 0.55 mM and 34,100 min(-1), respectively. Substrate binding sites and catalytic center amino acid residues based on those from known GSNORs were conserved in this enzyme, and the corresponding roles were verified using site-directed mutagenesis. Therefore, we demonstrated the presence of GSNOR in a filamentous fungus for the first time. PMID- 26869608 TI - Id-1, Id-2, and Id-3 co-expression correlates with prognosis in stage I and II lung adenocarcinoma patients treated with surgery and adjuvant chemotherapy. AB - Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family have been shown to be involved in carcinogenesis. However, the roles of Id during lung adenocarcinoma (ADC) progression remain unclear. Eighty-eight ADC samples were evaluated for Id-1,2,3 level and angiogenesis (CD 34 and VEGF microvessel density) by immunohistochemistry and morphometry. The impact of these markers was tested on follow-up until death or recurrence. A significant difference between tumor and normal tissue was found for Id-1,2,3 expression (P < 0.01). In addition, high levels of nuclear Id-1 were associated with higher angiogenesis in the tumor stroma (P < 0.01). Equally significant was the association between patients in T1-stage and low cytoplasmic Id-2, as well as patients in stage-IIb and low Id-3. High cytoplasm Id-3 expression was also directly associated to lymph nodes metastasis (P = 0.05). Patients at stages I to III, with low Id-1 and Id-3 cytoplasm histoscores showed significant long metastasis-free survival time than those with high Id-1 or Id-3 expression (P = 0.04). Furthermore, high MVD CD34 and MVD-VEGF expression were associated with short recurrence-free survival compared to low MVD-CD34 and MVD-VEGF expressions (P = 0.04). Cox model analyses controlled for age, lymph node metastasis, and adjuvant treatments showed that nuclear Id-1, cytoplasmic Id-3, and MVD-CD34 were significantly associated with survival time. Median score for nuclear Id-1 and cytoplasmic Id-3 divided patients in two groups, being that those with increased Id-1 and Id-3 presented higher risk of death. Ids showed an independent prognostic value in patients with lung ADC, regardless of disease stage. Id-1 and Id-3 should be considered new target candidates in the development of personalized therapy in lung ADC. PMID- 26869609 TI - Refeeding Low Weight Hospitalized Adolescents With Anorexia Nervosa: A Multicenter Randomized Controlled Trial. AB - BACKGROUND: Refeeding patients with anorexia nervosa (AN) is associated with high morbidity and mortality. A lack of evidence from interventional studies has hindered refeeding practice and led to worldwide disparities in management recommendations. In the first randomized controlled trial in this area, we tested the hypothesis that refeeding adolescents with AN with a higher energy intake than what many guidelines recommend improved anthropometric outcomes without adversely affecting cardiac and biochemical markers associated with refeeding. MATERIALS AND METHODS: Participants aged 10-16 years with a body mass index (BMI) <78% of the median (mBMI) for age and sex were recruited from 6 UK hospitals and randomly allocated to start refeeding at 1200 kcal/d (n = 18, intervention) or 500 kcal/d (n = 18, control). RESULTS: Compared with controls, adolescents randomized to high energy intake had greater weight gain (mean difference between groups after 10 days of refeeding, -1.2% mBMI; 95% confidence interval, -2.4% to 0.0%; P = .05), but randomized groups did not differ statistically in QTc interval and other outcomes. The nadir in postrefeeding phosphate concentration was significantly related to percentage mBMI at the start of refeeding (baseline; P = .04) and baseline white blood cell count (P = .005) but not to baseline energy intake (P = .08). CONCLUSIONS: Refeeding adolescents with AN with a higher energy intake was associated with greater weight gain but without an increase in complications associated with refeeding when compared with a more cautious refeeding protocol-thus challenging current refeeding recommendations. PMID- 26869610 TI - Association of the Adductor Pollicis Muscle Thickness With Clinical Outcomes in Intensive Care Unit Patients. AB - BACKGROUND: Different parameters may be used to evaluate the nutrition status of individuals. However, their use in the critically ill is problematic, since the interference of acute disease or therapeutic measures on their results can affect their interpretation. The aim of this study was to assess whether measuring the adductor pollicis muscle is useful in identifying malnutrition and clinical outcomes in the intensive care unit (ICU). MATERIALS AND METHODS: In total, 127 patients were enrolled in this prospective observational study. Serum albumin levels, anthropometrics, adductor pollicis muscle (APM) thickness, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were measured for each patient upon admission. APM thickness (APMT) was measured while the patient's elbow was flexed at a 90-degree angle and the forearm resting on the patient's torso. RESULTS: The dominant and nondominant APMT were significantly correlated with all anthropometric measurements (r = 0.41-0.68, P < .001 and r = 0.42-0.66, P < .001 respectively). Multivariate regression analysis adjusted by other risk factors, including APACHE II score, serum albumin, and age, showed that among all anthropometric variables, the APMT has the highest correlation with mortality (odds ratio [OR], 5.6; 95% confidence interval [CI], 0.02-0.12; P < .001), length of stay >10 days (OR, 11.3; 95% CI, 4.42-29.1; P < .001), and organ failure (OR, 14.5; 95% CI, 6.5-38.4; P < .001). CONCLUSIONS: The results showed that APMT is a low-cost, reliable, and easy method to assess nutrition status and to predict the patient's outcomes in the ICU. PMID- 26869611 TI - The Role of Probiotics on the Microbiota: Effect on Obesity. AB - The microbiota and the human host maintain a symbiotic association. Nowadays, metagenomic analyses are providing valuable knowledge on the diversity and functionality of the gut microbiota. However, with regard to the definition of a "healthy microbiota" and the characterization of the dysbiosis linked to obesity, there is still not a clear answer. Despite this fact, attempts have been made to counteract obesity through probiotic supplementation. A literature search of experimental studies relevant to the topic was performed in PubMed database with the keywords "probiotic" and "obesity" and restricted to those with "Lactobacillus" or "Bifidobacterium" in the title. So far, evidence of an antiobesity effect of different lactobacilli and bifidobacteria has been mainly obtained from animal models of dietary-induced obesity. Using these experimental models, a substantial number of studies have reported reductions in weight gain and, in particular, fat tissue mass at different locations following administration of bacteria, as compared with controls. Antiatherogenic and anti inflammatory effects-including regulation of expression of lipogenic and lipolytic genes in the liver, reduction in liver steatosis, improvement of blood lipid profile and glucose tolerance, decreased endotoxemia, and regulation of inflammatory pathways-are also reported in many of them. The number of human studies focused on probiotic administration for obesity management is still very scarce, and it is too soon to judge their potential efficacy, especially when considering the fact that the actions of probiotics are always strain specific and the individual response varies according to intrinsic factors, the overall composition of diet, and their interactions. PMID- 26869607 TI - Disordered haematopoiesis and athero-thrombosis. AB - Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero thrombosis. PMID- 26869612 TI - Challenges in Diagnosis and Treatment of Wernicke Encephalopathy: Report of 2 Cases. AB - BACKGROUND: Wernicke encephalopathy (WE) is a medical emergency caused by thiamine deficiency, characterized by cerebellar ataxia, ophthalmoplegia, and cognitive disturbances that may progress to Korsakoff amnesia. We describe 2 patients with WE who needed high-dose and long-term treatment with thiamine to obtain neurological improvement and recovery. CASE DESCRIPTION: The first patient was a woman diagnosed with non-Hodgkin lymphoma. After a gastrointestinal infection, she developed depression, memory loss, disorientation, behavioral changes, and ataxic paraplegia. Brain magnetic resonance imaging (MRI) showed bilateral alterations in thalamic, frontal, and periaqueductal regions, suggestive of WE. The second patient was a man who lost 10 kg after surgical gastrectomy; he developed diplopia, ophthalmoplegia, cerebellar ataxia, lower limb paresthesias, and amnesia. A brain MRI demonstrated contrast enhancement of mammillary bodies, compatible with WE. OUTCOME: The patients were treated with intramuscular (IM) thiamine (1200 mg/d for 2 months and 900 mg/d for a month, respectively) with gradual cognitive and behavioral improvement and brain MRI normalization, while ataxia and oculomotion improved in following months. In both patients, thiamine was gradually reduced to IM 200 mg/d and continued for a year, without clinical relapses. CONCLUSIONS: There is no consensus about dosage, frequency, route, and duration of thiamine administration in WE treatment. Based on our cases, we recommend treating patients with WE with higher doses of IM thiamine for a longer time than suggested (900-1200 mg/d for 1-2 months, in our cases) and to gradually reduce dosage after clinical and radiological improvement, maintaining IM 200 mg/d dosage for at least 1 year. PMID- 26869613 TI - Hypophosphatemia, Hypomagnesemia, and Hypokalemia in Pediatric Patients Before and During Exclusive Individualized Parenteral Nutrition. AB - BACKGROUND: Hypophosphatemia, hypomagnesemia, and hypokalemia occur in patients receiving parenteral nutrition (PN), mainly when the body's stores are depleted due to fasting or inflammation. Although these disorders are potentially fatal, few studies have reported the incidence in the pediatric population. METHODS: This study evaluated, in a historical cohort of pediatric patients, the prevalence of hypophosphatemia, hypokalemia, and hypomagnesaemia until 48 hours before initiation of PN infusion (P1) and from days 1-4 (P2) and days 5-7 (P3) of PN infusion and investigated if malnutrition, calories, and protein infusion were correlated to these disorders. RESULTS: Malnutrition was present in 32.8% (n = 119) of the subjects; 66.4% of the patients were in the pediatric intensive care unit. Survival rate was 86.6%. P1 had the highest prevalence of mineral disorders, with 54 events (58.1%; P2, n = 35, 37.6%; P3, n = 4, 4.3%). Hypokalemia events were related to malnutrition (odds ratio, 2.79; 95% confidence interval, 1.09-7.14; P = .045). In the first 7 days, infused calories were below the amount recommended by current guidelines in up to 84.9% of patients, and protein infused was adequate in up to 75.7%. Protein infused above the recommendation in the first 4 days was related to hypomagnesaemia (odds ratio, 5.66; 95% confidence interval, 1.24-25.79; P = .033). CONCLUSION: Hypophosphatemia, hypokalemia, and hypomagnesemia were frequent in hospitalized pediatric patients before and during the first 4 days of PN infusion. Patients with malnutrition had more chances of having hypokalemia, and those who received high protein infusion had an increased chance of developing hypomagnesemia. PMID- 26869614 TI - Treasury bails out England's health department. PMID- 26869615 TI - Positive and Negative Affect in Children Living in Refugee Camps: Assessing the Psychometric Proprieties and Factorial Invariance of the PANAS-C in the Gaza Strip. AB - In the present study, we assessed the psychometric proprieties of the Positive and Negative Affect Scale-Child Version (PANAS-C) in a large sample of Palestinian children (N = 1,376) of different age ranges living in refugee camps. In particular, we used standard confirmatory factor analysis to test competing factor structures for the PANAS-C, with a view to developing a stable version of the instrument, suitable for speedy administration in applied and research settings in the contexts of military violence. Four alternative models of the PANAS-C were evaluated: unidimensional; two-dimensional with independent PA and NA scales and covariance of item-level errors unallowed; two-dimensional with dependent PA and NA scales and covariance of item-level errors unallowed; and two dimensional with dependent PA and NA scales and covariance of item-level errors. The results of the statistical analysis supported a 20-item measurement model comprising the PANAS-C20 Arabic version for children. The items in this best fitting model loaded on two different and negatively correlated factors. These findings encourage full adoption of the PANAS-C20 as a tool for assessing both PA and NA in Palestinian children living in contexts of warfare. PMID- 26869616 TI - Atypical glandular cells on cervical cytology. PMID- 26869617 TI - Efficient Genome Editing in Chicken DF-1 Cells Using the CRISPR/Cas9 System. AB - In recent years, genome engineering technology has provided unprecedented opportunities for site-specific modification of biological genomes. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 is one such means that can target a specific genome locus. It has been applied in human cells and many other organisms. Meanwhile, to efficiently enrich targeted cells, several surrogate systems have also been developed. However, very limited information exists on the application of CRISPR/Cas9 in chickens. In this study, we employed the CRISPR/Cas9 system to induce mutations in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), ATP synthase epsilon subunit (ATP5E), and ovalbumin (OVA) genes in chicken DF-1 cells. The results of T7E1 assays showed that the mutation rate at the three different loci was 0.75%, 0.5%, and 3.0%, respectively. In order to improve the mutation efficiency, we used the Puro(R) gene for efficient enrichment of genetically modified cells with the surrogate reporter system. The mutation rate, as assessed via the T7E1 assay, increased to 60.7%, 61.3%, and 47.3%, and subsequent sequence analysis showed that the mutation efficiency increased to 94.7%, 95%, and 95%, respectively. In addition, there were no detectable off-target mutations in three potential off target sites using the T7E1 assay. As noted above, the CRISPR/Cas9 system is a robust tool for chicken genome editing. PMID- 26869618 TI - Detecting and Quantifying Changing Selection Intensities from Time-Sampled Polymorphism Data. AB - During his well-known debate with Fisher regarding the phenotypic dataset of Panaxia dominula, Wright suggested fluctuating selection as a potential explanation for the observed change in allele frequencies. This model has since been invoked in a number of analyses, with the focus of discussion centering mainly on random or oscillatory fluctuations of selection intensities. Here, we present a novel method to consider nonrandom changes in selection intensities using Wright-Fisher approximate Bayesian (ABC)-based approaches, in order to detect and evaluate a change in selection strength from time-sampled data. This novel method jointly estimates the position of a change point as well as the strength of both corresponding selection coefficients (and dominance for diploid cases) from the allele trajectory. The simulation studies of this method reveal the combinations of parameter ranges and input values that optimize performance, thus indicating optimal experimental design strategies. We apply this approach to both the historical dataset of P. dominula in order to shed light on this historical debate, as well as to whole-genome time-serial data from influenza virus in order to identify sites with changing selection intensities in response to drug treatment. PMID- 26869619 TI - Accuracy of Genomic Prediction in Switchgrass (Panicum virgatum L.) Improved by Accounting for Linkage Disequilibrium. AB - Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height, and heading date. Marker data were produced for the families' parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs. PMID- 26869620 TI - Evolution of Plant Phenotypes, from Genomes to Traits. PMID- 26869622 TI - Unusual presentation of a familiar pathology: chronic appendicitis. AB - We present a case of a man who experienced night sweats, abdominal pain and fever for over 3 months, with incomplete response to broad-spectrum intravenous antibiotics. Although CT imaging was insufficient to identify the cause for his chronic abdominal pain, the abnormality of a 'misty mesentery' was crucial in guiding further investigation. The final diagnosis of chronic appendicitis was made through laparoscopic and pathological examination. This case highlights the utility of a collaborative diagnostic effort between disciplines. Chronic appendicitis can cause lingering abdominal pain. Early recognition and appropriate referral can save patients months and even years of unnecessary suffering. PMID- 26869621 TI - Whole Genome Comparison Reveals High Levels of Inbreeding and Strain Redundancy Across the Spectrum of Commercial Wine Strains of Saccharomyces cerevisiae. AB - Humans have been consuming wines for more than 7000 yr . For most of this time, fermentations were presumably performed by strains of Saccharomyces cerevisiae that naturally found their way into the fermenting must . In contrast, most commercial wines are now produced by inoculation with pure yeast monocultures, ensuring consistent, reliable and reproducible fermentations, and there are now hundreds of these yeast starter cultures commercially available. In order to thoroughly investigate the genetic diversity that has been captured by over 50 yr of commercial wine yeast development and domestication, whole genome sequencing has been performed on 212 strains of S. cerevisiae, including 119 commercial wine and brewing starter strains, and wine isolates from across seven decades. Comparative genomic analysis indicates that, despite their large numbers, commercial strains, and wine strains in general, are extremely similar genetically, possessing all of the hallmarks of a population bottle-neck, and high levels of inbreeding. In addition, many commercial strains from multiple suppliers are nearly genetically identical, suggesting that the limits of effective genetic variation within this genetically narrow group may be approaching saturation. PMID- 26869623 TI - Traumatic brain injury and the evidence for its management. AB - A 29-year-old man presented to a major trauma centre with traumatic brain injury. Following cranial decompression, the patient was admitted to the intensive care unit for medical management and monitoring. This case report reviews the evidence for the management of traumatic brain injury. PMID- 26869625 TI - An 86-year-old man with acute abdominal pain. AB - An 86-year-old man presented with severe pain in the upper abdomen along with fever. On physical examination, we found an arterial blood pressure of 84/43 mm Hg, a heart rate of 80 bpm and a temperature of 38.3 degrees C. The abdomen was painful and peristalsis was absent. Empiric antibiotic therapy for sepsis was started with amoxicillin/clavulanate and gentamicin. CT scan of the abdomen revealed an emphysematous cholecystitis. Percutaneous ultrasound-guided cholecystostomy was applied. Bile cultures revealed Clostridium perfringens. Emphysematous cholecystitis is a life-threatening form of acute cholecystitis that occurs as a consequence of ischaemic injury to the gallbladder, followed by translocation of gas-forming bacteria (ie, C. perfringens, Escherichia coli, Klebsiella and Streptococci). The mortality associated with emphysematous cholecystitis is higher than in non-emphysematous cholecystitis (15% vs 4%). Therefore, early diagnosis with radiological imaging is of vital importance. PMID- 26869624 TI - Spontaneous lymphocoele: an unusual cause of an axillary mass. AB - A lymphocoele or cystic hygroma is a benign lymphatic malformation that usually presents as a congenital mass in infancy. These masses are most common in the cervicofacial region and more rarely occur elsewhere in the body. Spontaneous, atraumatic presentation in adulthood is extremely rare. We present a case of a 59 year-old woman who presented with a fluctuant mass in the axilla, which was diagnosed as a lymphocoele. Initial management by ultrasound-guided aspiration of the cyst proved unsuccessful due to recurrence. Surgical excision of the cyst was then successfully performed and histological analysis proved the diagnosis. The incidence of adult-onset lymphocoele without a history of prior trauma or operation is rare. This case report adds to the literature and reviews the various management strategies that have been successfully employed. PMID- 26869626 TI - CT findings in type IV hiatus hernia involving the pancreas. PMID- 26869627 TI - Dysphagia and aspiration as the only manifestations of a stroke. AB - A 56-year-old patient was admitted to our hospital, presenting with dysphagia as the only symptom. He was very concerned about this difficulty in swallowing. Diseases of the upper digestive tract were suspected, but further investigations revealed a neurological disorder. He had suffered a brain stem stroke and, as a consequence, developed an aspiration pneumonia. What seemed a digestive disorder was indeed a brain stem stroke, therefore we had to deal with the diverse impacts of this condition. PMID- 26869628 TI - Trismus, the first symptom in a challenging diagnosis of Tetanus. AB - Tetanus is a severe, life-threatening infectious disease present worldwide. The incidence of this disease is very low in developed countries, and practitioners are unfamiliar with its symptoms and signs, resulting in late diagnosis and low recovery rate. Furthermore, main symptoms, such as trismus, are often associated with several confounding factors: these may lead the physician to send patients towards an incorrect diagnostic management and the calling on of wrong specialists. This case focuses on the importance of considering tetanus in the differential diagnosis of trismus associated with systemic symptoms, and discusses the clinical implications of an initial wrong diagnostic pathway. PMID- 26869629 TI - Acute myeloid leukemia patients' clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts. PMID- 26869632 TI - Heartbeat: Biomarkers and pulmonary artery hypertension. PMID- 26869631 TI - Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia. AB - Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13-5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34(+) and CD8(+) cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34(+) and CD8(+) leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical. TRIALS: gov with the number NC01423747. PMID- 26869633 TI - The quest for biomarker discovery in pulmonary arterial hypertension: the right takes lessons from the left. PMID- 26869630 TI - Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival. AB - Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, P<0.0001) recovery, lower risk of grade II-IV acute graft-versus-host disease (HR=0.26, P<0.0001) and chronic graft-versus-host disease (HR=0.06, P<0.0001). Haplo-cord was associated with decreased risk of relapse (HR 0.48, P=0.001). Graft-versus-host disease-free, relapse-free survival was superior with haplo cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID- 26869634 TI - Ultrasound contrast during stress echo: for obese patients, but not only. PMID- 26869635 TI - Galectin-3 and aldosterone as potential tandem biomarkers in pulmonary arterial hypertension. AB - BACKGROUND: Several studies have identified circulating biomarkers to be associated with the presence and severity of pulmonary arterial hypertension (PAH). Recent evidence supports a role for galectin-3 (Gal-3) and the mineralcorticoid aldosterone in left ventricular failure. However, studies on aldosterone together with Gal-3 in PAH are lacking. OBJECTIVE: We investigated a novel Aldosterone-galectin-3 (Gal-3) tandem and several other potential PAH biomarkers and their association with the disease severity. METHODS: A total of 57 patients, 41 with idiopathic PAH. (IPAH) and 16 with PAH associated with connective tissue disease (CTD), and 8 age-matched, non-relative controls were studied. Gal-3, aldosterone and other potential protein plasma concentrations were measured by single ELISA and multi-array MSD (Meso Scale Discovery) technology. RESULTS: Gal-3 values were increased in both patients with IPAH (12.2+/-0.6 ng/mL; p<0.05) and with PAH-CTD (14.1+/-1.6 ng/mL; p<0.05) versus control (8.5+/-0.9 ng/mL), while aldosterone was significantly elevated in IPAH only (248.5+/-38.8 pg/mL vs control 71.9+/-18.2 pg/mL; p<0.05). In addition, aldosterone, Gal-3, and N-terminal pro-brain natriuretic peptide (NT-proBNP) values were all higher in patients in WHO functional class II-III versus PAH functional class I or controls. The vascular injury marker intercellular adhesion molecule 1 (ICAM-1) was increased in IPAH and PAH-CTD versus controls (559.5+/ 18.2 pg/mL and 734.1+/-59.4 pg/mL vs controls 394.8+/-39.3 pg/mL, p<0.05, p<0.0001, respectively), whereas vascular cell adhesion molecule 1 (VCAM-1) and proinflammatory, anti-angiogenic interleukin-12 (IL-12) were elevated in PAH-CTD only (879.5+/-110.0 pg/mL and 391.2+/-70.3 pg/mL vs controls 489.8+/-44.6 pg/mL, p<0.01, and 102.1+/-15.2 pg/mL, p<0.01, respectively). CONCLUSIONS: Heightened Gal-3 and aldosterone plasma concentrations in PAH patients indicate a role for Gal-3 signalling in the pathobiology of IPAH and PAH-CTD, and may serve as biomarkers for functional status and progression of disease. PMID- 26869640 TI - Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis. AB - OBJECTIVE: Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. METHODS: PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. RESULTS: A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, p<0.001) in unmatched groups and 0.41 (95% CI 0.31 to 0.54, p<0.001) in the propensity-matched groups (matched for baseline variables). For patients who had surgical intervention at 7 days or less, OR of all-cause mortality was 0.61 (95% CI 0.39 to 0.96, p=0.034) and in those who had surgical intervention within 8-20 days, the OR of mortality was 0.64 (95% CI 0.48 to 0.86, p=0.003) compared with conservative management. In propensity-matched groups, the OR of mortality in patients with surgical intervention at 7 days or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and in the subgroup of patients who underwent surgery between 8 and 20 days was 0.51 (95% CI 0.35 to 0.72, p<0.001). There was no significant difference in in-hospital mortality, embolisation, heart failure and recurrence of endocarditis between the overall unmatched cohorts. CONCLUSION: The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis. PMID- 26869641 TI - Trimethylamine N-oxide and prognosis in acute heart failure. AB - OBJECTIVE: Acute heart failure (AHF) is associated with high mortality and morbidity. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, has reported association with mortality risk in chronic HF but this association in AHF is still unknown. The present study investigated TMAO in patients admitted to hospital with AHF, and association of circulating levels with prognosis. METHODS: In total, 972 plasma samples were analysed for TMAO concentration by liquid chromatography-mass spectrometry. Associations with in-hospital mortality (72 events), all-cause mortality (death, 268 events) and a composite of death or rehospitalisation due to HF (death/HF, 384 events) at 1 year were examined. RESULTS: TMAO improved risk stratification for in-hospital mortality in combination with current clinical scorings (OR>=1.13, p<=0.014). TMAO tertile analyses reported a graded risk in adverse outcome within 1 year (OR>=1.61, p<=0.004) and improved outcome prediction when stratified as none, one or both biomarker(s) elevated in combination with N-terminal pro B-type natriuretic peptide (NT-proBNP) (OR>=2.15, p<=0.007). TMAO was independently predictive for death and death/HF when corrected for cardiac risk factors (HR>=1.16, p<=0.037); however, this ability was weakened when indices of renal function were included, possibly due to multicollinearity. CONCLUSIONS: TMAO contributed additional information on patient stratification for in-hospital mortality of AHF admissions using available clinical scores that include renal indices. Furthermore, elevated levels were associated with poor prognosis at 1 year and combination of TMAO and NT-proBNP provided additional prognostic information. TMAO was a univariate predictor of death and death/HF, and remained an independent predictor until adjusted for renal confounders. PMID- 26869643 TI - Demographics of the US Oncology Workforce. PMID- 26869645 TI - Targeting Programmed Death 1/Programmed Death Ligand 1 in Lymphoma: A Game Changer. PMID- 26869644 TI - Where Do Programmed Death-1 Inhibitors Fit in the Management of Malignant Lymphoma? AB - Tumor-specific cytotoxic T cells have the capacity to target and eradicate malignant B cells in patients with Hodgkin and non-Hodgkin lymphoma; however, multiple mechanisms, including regulatory T cells, immunosuppressive ligands, and immune exhaustion, suppress an effective antitumor immune response. One mechanism that is used by malignant cells to inhibit the immune response is overexpression of programmed death ligand 1 or 2 (PD-L1 or PD-L2) on the cancer cell surface. These ligands interact with the programmed death-1 (PD-1) receptor expressed on intratumoral T cells and provide an inhibitory signal, thereby suppressing the antitumor immune response. Monoclonal antibodies that block PD-1 signaling prevent T-cell inhibition and promote a T-cell-mediated antilymphoma response. Blocking antibodies that are directed against PD-1 or PD-L1 are currently being tested in patients with lymphoma and have shown remarkable efficacy, particularly in patients with relapsed Hodgkin lymphoma. On the basis of the promising activity of this approach, PD-1 inhibitors are being used as single-agent therapy in patients with relapsed Hodgkin lymphoma, and these inhibitors are also being tested in combination with standard chemotherapy or targeted agents in ongoing clinical trials. PMID- 26869642 TI - ALS-linked protein disulfide isomerase variants cause motor dysfunction. AB - Disturbance of endoplasmic reticulum (ER) proteostasis is a common feature of amyotrophic lateral sclerosis (ALS). Protein disulfide isomerases (PDIs) areERfoldases identified as possibleALSbiomarkers, as well as neuroprotective factors. However, no functional studies have addressed their impact on the disease process. Here, we functionally characterized fourALS-linked mutations recently identified in two majorPDIgenes,PDIA1 andPDIA3/ERp57. Phenotypic screening in zebrafish revealed that the expression of thesePDIvariants induce motor defects associated with a disruption of motoneuron connectivity. Similarly, the expression of mutantPDIs impaired dendritic outgrowth in motoneuron cell culture models. Cellular and biochemical studies identified distinct molecular defects underlying the pathogenicity of thesePDImutants. Finally, targetingERp57 in the nervous system led to severe motor dysfunction in mice associated with a loss of neuromuscular synapses. This study identifiesERproteostasis imbalance as a risk factor forALS, driving initial stages of the disease. PMID- 26869646 TI - Immune Checkpoint Inhibition: A New Era in Lymphoma Treatment. PMID- 26869647 TI - Multimodality Therapy for Limited-Stage Small-Cell Lung Cancer. AB - Limited-stage small-cell lung cancer (SCLC) occurs in only one third of patients with SCLC, but it is potentially curable. Combined-modality therapy (chemotherapy and radiotherapy) has long been the mainstay of therapy for this condition, but more recent data suggest a role for surgery in early-stage disease. Prophylactic cranial irradiation seems to improve outcomes in patients who have responded to initial therapy. This review addresses the practical aspects of staging and treatment of patients with limited-stage SCLC. PMID- 26869648 TI - Small-Cell Lung Cancer: New Directions for Systemic Therapy. PMID- 26869649 TI - Is This As Good As It Gets? PMID- 26869650 TI - Breast Cancer in Women Older Than 80 Years. AB - Breast cancer is the most common cancer in women, with an incidence that rises dramatically with age. The average age at diagnosis of breast cancer is 61 years, and the majority of woman who die of breast cancer are age 65 years and older. Major improvements in public health and medical care have resulted in dramatic increases in longevity. The oldest old (those age 80 years and older) are a rapidly expanding group and now comprise 9 million members of the US population. The treatment of individuals who are age 80 years and older is complex and involves clearly defining the goals and value of treatment while also weighing risks, such as the potential effects of treatment on functional loss and quality of life. Limited evidence-based treatment guidelines exist for the caring of this older cohort of patients with breast cancer. Data from clinical trials that enroll primarily younger patients lack the information needed to estimate the likelihood of toxicities that can be life changing in older adults. Clinicians who make treatment recommendations should place the available evidence in the context of the patient's life expectancy and geriatric assessment results that include an evaluation of a patient's functional status, comorbidities, cognition, social support, nutritional status, and psychological state. Furthermore, these decisions should be placed in the context of the patient's goals for treatment, preferences, and values. This review summarizes the current literature and focuses on the role of geriatric assessment in treatment recommendations for patients age 80 years and older with early and metastatic breast cancer. PMID- 26869651 TI - Treatment of Breast Cancer in Women Older Than 80 Years Is a Complex Task. PMID- 26869652 TI - Geriatricizing Oncology Care: Older Women With Breast Cancer. PMID- 26869653 TI - Cancer Staging in Electronic Health Records: Strategies to Improve Documentation of These Critical Data. PMID- 26869654 TI - Benefits and Pitfalls of Using Administrative Data to Study Hospitalization Patterns in Patients With Cancer Treated With Chemotherapy. PMID- 26869655 TI - ReCAP: Hospitalizations in Older Adults With Advanced Cancer: The Role of Chemotherapy. AB - PURPOSE: Hospital readmissions are often cited as a marker of poor quality of care. Limited data suggest some readmissions may be preventable depending upon definitions and available outpatient support. METHODS: General criteria to define preventable and not preventable admissions were developed before data collection began. The records of sequential nonsurgical oncology readmissions were reviewed independently by two reviewers. When the reviewers disagreed about assigning admissions as preventable or not preventable, a third reviewer was the tie breaker. The reasons for assigning admissions as preventable or not preventable were analyzed. RESULTS: Seventy-two readmissions occurring among 69 patients were analyzed. The first two reviewers agreed that 18 (25%) of 72 were preventable and that 29 (40%) of 72 were not. A third reviewer found four of the split 25 cases to be preventable; therefore, the consensus preventability rate was 22 (31%) of 72. The most common causes of preventability were overwhelming symptoms in patients who qualified for hospice but were not participating in hospice and insufficient communication between patients and the care team about symptom burden. The most common reason for assignment of a not preventable admission was a high symptom burden among patients without strong indications for hospice or for whom aggressive outpatient management was inadequate. The median survival after readmission was 72 days. CONCLUSION: A substantial proportion of oncology readmissions could be prevented with better anticipation of symptoms in high-risk ambulatory patients and enhanced communication about symptom burden between patients and physicians before an escalation that leads to an emergency department visit. Managing symptoms in patients who are appropriate for hospice is challenging. Readmission is a marker of poor prognosis. PMID- 26869657 TI - Meningeal Myelomatosis. PMID- 26869656 TI - ReCAP: Detection of Potentially Avoidable Harm in Oncology From Patient Medical Records. AB - PURPOSE: Widespread consensus exists about the importance of addressing patient safety issues in oncology, yet our understanding of the frequency, spectrum, and preventability of adverse events (AEs) across cancer care is limited. METHODS: We developed a screening tool to detect AEs across cancer care settings through medical record review. Members of the study team reviewed the scientific literature and obtained structured input from an external multidisciplinary panel of clinicians by using a modified Delphi process. RESULTS: The screening tool comprises 76 triggers-readily identifiable findings to screen for possible AEs that occur during cancer care. Categories of triggers are general care, vital signs, medication related, laboratory tests, other orders, and consultations. CONCLUSION: Although additional testing is required to assess its performance characteristics, this tool may offer an efficient mechanism for identifying possibly preventable AEs in oncology and serve as an instrument for quality improvement. PMID- 26869661 TI - Multidisciplinary Management of Chronic Pain. A Practical Guide for Clinicians. PMID- 26869658 TI - Reducing the Time From Diagnosis to Treatment of Patients With Stage II/III Rectal Cancer at a Large Public Hospital. AB - Curative-intent therapy for stage II/III rectal cancer is necessarily complex. Current guidelines by the National Comprehensive Cancer Network recommend preoperative concurrent chemoradiation followed by resection and additional adjuvant chemotherapy. We used standard quality improvement methodology to implement a cost-effective intervention that reduced the time from diagnosis to treatment of patients with stage II/III rectal cancer by approximately 30% in a large public hospital in Houston, Texas. Implementation of the program resulted in a reduction in time from pathologic diagnosis to treatment of 29% overall, from 62 to 44 days. These gains were cost neutral and resulted from improvements in scheduling and coordination of care alone. Our results suggest that: (1) quality improvement methodology can be successfully applied to multidisciplinary cancer care, (2) effective interventions can be cost neutral, and (3) effective strategies can overcome complexities such as having multiple sites of care, high staff turnover, and resource limitations. PMID- 26869662 TI - Outcomes of minimally invasive lung transplantation in a single centre: the routine approach for the future or do we still need clamshell incision? AB - OBJECTIVES: Minimally invasive lung transplantation (MILT) via bilateral anterior thoracotomies has emerged as a novel surgical strategy with potential patient benefits when compared with transverse thoracosternotomy (clamshell incision, CS). The aim of this study is to compare MILT with CS by focusing on operative characteristics, postoperative organ function and support and mid-term clinical outcomes at Harefield Hospital. METHODS: It was a retrospective observational study evaluating all bilateral sequential lung transplants between April 2010 and November 2013. RESULTS: CS was performed in 124 patients and MILT in 70 patients. Skin-to-skin surgical time was less in the MILT group [285 (265, 339) min] compared with CS [380 (306, 565) min] and MILT-cardiopulmonary bypass [426 (360, 478) min]. Ischaemic time was significantly longer (502 +/- 116 vs 395 +/- 145 min) in the MILT group compared with CS (P < 0.01). Early postoperative physiological variables were similar between groups. Patients in the MILT group required less blood [2 (0, 4) vs 3 (1, 5) units, P = 0.16] and platelet transfusion [0 (0, 1) vs 1 (0, 2) units, P < 0.01]. The median duration of mechanical ventilation was shorter (26 vs 44 h, P < 0.01) and intensive therapy unit stay was 2 days shorter (5 vs 7) in the MILT group. While overall survival was similar, fraction of expired volume in 1 s (FEV1) and forced vital capacity (FVC) were consistently higher in the MILT group compared with CS during mid-term follow-up after transplantation. Specifically, FEV1 and FVC were, respectively, 86 +/- 21 and 88 +/- 18% predicted in the MILT group compared with 74 +/- 21 and 74 +/- 19% predicted in the CS group (P < 0.01) at the 6-month follow-up. CONCLUSIONS: MILT was successfully introduced at our centre as a novel operative strategy. Despite longer ischaemic times and a more complex operation and management, MILT appears to offer early postoperative and mid-term clinical benefits compared with our traditional approach of clamshell operations. These observations warrant larger definite studies to further evaluate the impact of MILT on physiological, clinical and patient-reported outcomes. PMID- 26869663 TI - Two-stage operation for Stanford type A acute aortic dissection originating from Kommerell's diverticulum. AB - We report a rare case of Stanford type A acute aortic dissection involving an aberrant right subclavian artery and originating from Kommerell's diverticulum in a 52-year old man. Initially, as an emergency measure, total arch replacement and right axillary artery reconstruction were performed. However, due to the subsequent enlargement of the false lumen, thoracic endovascular aortic repair and right subclavian artery coiling were performed successfully 5 months after the first operation. Herein, we describe surgical management approaches for the treatment of a Stanford type A acute aortic dissection with aberrant right subclavian artery. PMID- 26869664 TI - Understanding the Areas and Correlates of Diabetes-Related Distress in Parents of Teens With Type 1 Diabetes. AB - OBJECTIVE: To identify the unique areas of diabetes-related distress (DD) for parents of teens with type 1 diabetes and parent and teen characteristics associated with DD. METHODS: Areas of DD were developed from structured interviews and translated into 46 survey items. Items were analyzed with exploratory factor analysis (EFA). RESULTS: An EFA with 332 parents (88% mothers) reduced items to four Parent Diabetes Distress Scale (PDDS) factors (20 items, alpha = .94): Personal, Teen Management, Parent/Teen Relationship, and Healthcare Team Distress. Parent DD was higher among fathers, younger or single parents, parents of teens with higher hemoglobin A1c or severe low blood glucose levels, authoritarian parenting, depressive symptoms, and low emotional support. CONCLUSIONS: 4 areas of parent DD were identified using a newly developed measure, the PDDS. DD was associated with family demographic, teen diabetes status, and parent contextual factors, and can help identify parents who may be more vulnerable to DD. PMID- 26869665 TI - Examining Biopsychosocial Factors in Relation to Multiple Pain Features in Pediatric Sickle Cell Disease. AB - OBJECTIVE: To examine biopsychosocial variables in relation to multiple pain features in pediatric sickle cell disease (SCD). METHODS: 76 children with SCD (M = 14.05, SD = 3.26), ages 8-19 years, and 70 caregivers completed measures of coping, mood, and family functioning and reported on multiple pain features via retrospective interviews during routine hematological visits. Sickle cell genotype and health care utilization were collected via medical record review. Using hierarchical regression, biological (genotype), child psychological (coping and mood), and social factors (caregiver coping and family functioning) were evaluated in relation to multiple pain features. RESULTS: Genotype was associated with pain intensity, and child psychological factors were associated with pain frequency. Multiple biopsychosocial factors were related to health care utilization. CONCLUSIONS: Biopsychosocial factors may have distinct relationships with pain features in pediatric SCD. Understanding these relationships may refine the biopsychosocial model and inform integrated medical and psychosocial approaches in SCD. PMID- 26869666 TI - Paid family leave's effect on hospital admissions for pediatric abusive head trauma. AB - Paediatric abusive head trauma (AHT) is a leading cause of fatal child maltreatment among young children. Current prevention efforts have not been consistently effective. Policies such as paid parental leave could potentially prevent AHT, given its impacts on risk factors for child maltreatment. To explore associations between California's 2004 paid family leave (PFL) policy and hospital admissions for AHT, we used difference-in-difference analyses of 1995 2011 US state-level data before and after the policy in California and seven comparison states. Compared with seven states with no PFL policies, California's 2004 PFL showed a significant decrease in AHT admissions in both <1 and <2-year olds. Analyses using additional data years and comparators could yield different results. PMID- 26869667 TI - Inhibition of KV7 Channels Protects the Rat Heart against Myocardial Ischemia and Reperfusion Injury. AB - The voltage-gated KV7 (KCNQ) potassium channels are activated by ischemia and involved in hypoxic vasodilatation. We investigated the effect of KV7 channel modulation on cardiac ischemia and reperfusion injury and its interaction with cardioprotection by ischemic preconditioning (IPC). Reverse-transcription polymerase chain reaction revealed expression of KV7.1, KV7.4, and KV7.5 in the left anterior descending rat coronary artery and all KV7 subtypes (KV7.1-KV7.5) in the left and right ventricles of the heart. Isolated hearts were subjected to no-flow global ischemia and reperfusion with and without IPC. Infarct size was quantified by 2,3,5-triphenyltetrazolium chloride staining. Two blockers of KV7 channels, XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone] (10 uM) and linopirdine (10 uM), reduced infarct size and exerted additive infarct reduction to IPC. An opener of KV7 channels, flupirtine (10 uM) abolished infarct size reduction by IPC. Hemodynamics were measured using a catheter inserted in the left ventricle and postischemic left ventricular recovery improved in accordance with reduction of infarct size and deteriorated with increased infarct size. XE991 (10 uM) reduced coronary flow in the reperfusion phase and inhibited vasodilatation in isolated small branches of the left anterior descending coronary artery during both simulated ischemia and reoxygenation. KV7 channels are expressed in rat coronary arteries and myocardium. Inhibition of KV7 channels exerts cardioprotection and opening of KV7 channels abrogates cardioprotection by IPC. Although safety issues should be further addressed, our findings suggest a potential role for KV7 blockers in the treatment of ischemia-reperfusion injury. PMID- 26869668 TI - Elucidation of the Mechanisms through Which the Reactive Metabolite Diclofenac Acyl Glucuronide Can Mediate Toxicity. AB - We have previously reported that mice lacking the efflux transporter Mrp3 had significant intestinal injury after toxic diclofenac (DCF) challenge, and proposed that diclofenac acyl glucuronide (DCF-AG), as a substrate of Mrp3, played a part in mediating injury. Since both humans and mice express the uptake transporter OATP2B1 in the intestines, OATP2B1 was characterized for DCF-AG uptake. In vitro assays using human embryonic kidney (HEK)-OATP2B1 cells demonstrated that DCF-AG was a substrate with a maximal velocity (Vmax) and Km of 17.6 +/- 1.5 pmol/min per milligram and 14.3 +/- 0.1 MUM, respectively. Another key finding from our in vitro assays was that DCF-AG was more cytotoxic compared with DCF, and toxicity occurred within 1-3 hours of exposure. We also report that 1 mM DCF-AG caused a 6-fold increase in reactive oxygen species (ROS) by 3 hours. Investigation of oxidative stress through inhibition of superoxide dismutase (SOD) revealed that DCF-AG had 100% inhibition of SOD at the highest tested dose of 1 mM. The SOD and ROS results strongly suggest DCF-AG induced oxidative stress in vitro. Lastly, DCF-AG was screened for pharmacologic activity against COX-1 and COX-2 and was found to have IC50 values of 0.620 +/- 0.105 and 2.91 +/- 0.36 MUM, respectively, which represents a novel finding. Since cyclooxygenase (COX) inhibition can lead to intestinal ulceration, it is plausible that DCF-AG can also contribute to enteropathy via COX inhibition. Taken in context, the work presented herein demonstrated the multifactorial pathways by which DCF-AG can act as a direct contributor to toxicity following DCF administration. PMID- 26869670 TI - Inhibition of Pim1 kinase, new therapeutic approach in virus-induced asthma exacerbations. AB - Therapeutic options to treat virus-induced asthma exacerbations are limited and urgently needed. Therefore, we tested Pim1 kinase as potential therapeutic target in human rhinovirus (HRV) infections. We hypothesised that inhibition of Pim1 kinase reduces HRV replication by augmenting the interferon-induced anti-viral response due to increased activity of the janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.Air-liquid interface (ALI) cultures of primary bronchial epithelial cells (PBECs) from healthy individuals and moderate-to-severe asthmatic volunteers were infected with HRV-16 with or without a specific Pim1 inhibitor; viral replication and induction of anti-viral responses were measured using RT-qPCR. Viral titres were measured by 50% tissue culture infective dose and release of interferon-gamma-induced protein 10 (IP-10) and RANTES protein assessed by ELISA. Phosphorylation of STAT-1 was determined using western blotting.Viral replication was reduced in ALI cultures of healthy and asthmatic PBECs treated with the Pim1 inhibitor. Using cultures from healthy donors, enhanced STAT-1 phosphorylation upon inhibition of Pim1 kinase activity resulted in increased mRNA expression of interferon-beta, interleukin-29, IP-10 and RANTES 12 h after infection and increased protein levels of IP-10 and RANTES 24 h after infection.We have identified Pim1 kinase as novel target to reduce viral replication in ALI cultures of PBECs. This may open new avenues for therapeutic interventions in virus-induced asthma exacerbations. PMID- 26869671 TI - Inflammatory bowel disease and risk of mortality in COPD. AB - Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD.Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Quebec, Canada, 1990-2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk.The COPD and asthma-COPD cohorts included 273 208 and 26 575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09-1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23 2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31-3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39-8.30).IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively. PMID- 26869673 TI - Urokinase plasminogen activator receptor polymorphisms and airway remodelling in asthma. PMID- 26869672 TI - Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes. AB - Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro.Expression of soluble/immunoreactive activin-A and its receptors was measured in serum, bronchoalveolar lavage fluid (BALF) and endobronchial biopsies from 16 healthy controls, 19 patients with mild/moderate asthma and 22 severely asthmatic patients. In vitro effects of activin-A on baseline and vascular endothelial growth factor (VEGF)-induced human endothelial cell angiogenesis, signalling and cytokine release were compared with BALF concentrations of these cytokines in vivo.Activin-A expression was significantly elevated in serum, BALF and bronchial tissue of the asthmatics, while expression of its protein receptors was reduced. In vitro, activin-A suppressed VEGF-induced endothelial cell proliferation and angiogenesis, inducing autocrine production of anti-angiogenic soluble VEGF receptor (R)1 and interleukin (IL)-18, while reducing production of pro angiogenic VEGFR2 and IL-17. In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis.Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo, where reduced basal expression of its receptors is observed particularly in severe asthma. PMID- 26869674 TI - Assessing small airway impairment in mild-to-moderate smoking asthmatic patients. PMID- 26869675 TI - Fertility outcomes in asthma: a clinical study of 245 women with unexplained infertility. AB - Evidence is increasing of an association between asthma and aspects of female reproduction. However, current knowledge is limited and furthermore relies on questionnaire studies or small populations. In a prospective observational cohort study to investigate whether time to pregnancy, the number of fertility treatments, and the number of successful pregnancies differ significantly between women with unexplained infertility with and without asthma.245 women with unexplained infertility (aged 23-45 years) underwent questionnaires and asthma and allergy testing while undergoing fertility treatment. 96 women entering the study had either a former doctor's diagnosis of asthma or were diagnosed with asthma when included. After inclusion they were followed for a minimum of 12 months in fertility treatment, until they had a successful pregnancy, stopped treatment, or the observation ended.The likelihood of achieving pregnancy was lower in women with asthma compared with those without asthma: median total time to pregnancy was 32.3 months in non-asthmatic women versus 55.6 months in those with asthma, hazard ratio 0.50 (95% confidence interval 0.34-0.74) p<0.001.Women with asthma had fewer successful pregnancies during fertility treatment, 39.6 versus 60.4% (p=0.002). Increasing age was of negative importance for expected time to pregnancy, especially among asthmatic women (interaction between age and asthma on time to pregnancy, p=0.001). Female asthmatics had a longer time to pregnancy and less often became pregnant than non-asthmatic women. Increasing age reduced the chances of conceiving especially among asthmatic women. The causal relationship between asthma and subfertility remains unclear. PMID- 26869676 TI - High-flow nasal oxygen for bronchoalveolar lavage in acute respiratory failure patients. PMID- 26869677 TI - First independent evaluation of QuantiFERON-TB Plus performance. PMID- 26869678 TI - Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy. AB - Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM 151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study.A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients. Subjects in three successive cohorts (1, 5, or 10 mg.kg(-1) versus placebo) received intravenous study drug on days 1, 3, 5, 8 and 15, and were followed-up to day 57.PRM-151 was well tolerated at all dose levels, with no serious adverse reactions. Administration of PRM-151 resulted in two- to eight-fold dose dependent increases in circulating pentraxin-2 levels. Forced vital capacity and 6-min walk test showed trends towards improvement in the combined PRM-151 dose groups. On high-resolution computed tomography scans, stable or improved lung volume unoccupied by interstitial lung abnormality was noted in some PRM-151 subjects compared to placebo subjects on day 57.The efficacy of PRM-151 in IPF remains to be investigated in dedicated future trials. PMID- 26869680 TI - A 3-week multimodal intervention involving high-intensity interval training in female cancer survivors: a randomized controlled trial. AB - To compare the effects of a 3-week multimodal rehabilitation involving supervised high-intensity interval training (HIIT) on female breast cancer survivors with respect to key variables of aerobic fitness, body composition, energy expenditure, cancer-related fatigue, and quality of life to those of a standard multimodal rehabilitation program. A randomized controlled trial design was administered. Twenty-eight women, who had been treated for cancer were randomly assigned to either a group performing exercise of low-to-moderate intensity (LMIE; n = 14) or a group performing high-intensity interval training (HIIT; n = 14) as part of a 3-week multimodal rehabilitation program. No adverse events related to the exercise were reported. Work economy improved following both HIIT and LMIE, with improved peak oxygen uptake following LMIE. HIIT reduced mean total body fat mass with no change in body mass, muscle or fat-free mass (best P < 0.06). LMIE increased muscle and total fat-free body mass. Total energy expenditure (P = 0.45) did not change between the groups, whereas both improved quality of life to a similar high extent and lessened cancer-related fatigue. This randomized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects. Here, HIIT and LMIE both improved work economy, quality of life and cancer-related fatigue, body composition or energy expenditure. Since the outcomes were similar, but HIIT takes less time, this may be a time-efficient strategy for improving certain aspects of the health of female cancer survivors. PMID- 26869679 TI - Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls. AB - We previously showed that increases in mean arterial pressure (MAP) following administration of midodrine hydrochloride (MH) and nitro-L-arginine methyl ester (L-NAME) resulted in increased mean cerebral blood flow velocity (MFV) during head-up tilt in hypotensive individuals with spinal cord injury (SCI) and question if this same association was evident during cognitive activation. Herein, we report MAP and MFV during two serial subtraction tasks (SSt) given before (predrug) and after (postdrug) administration of MH; (10 mg), L-NAME (1 mg/kg) or no drug (ND) in 15 subjects with SCI compared to nine able-bodied (AB) controls. Three-way factorial analysis of variance (ANOVA) models were used to determine significant main and interaction effects for group (SCI, AB), visit (MH, L-NAME, ND), and time (predrug, postdrug) for MAP and MFV during the two SSt. The three-way interaction was significant for MAP (F = 4.262; P = 0.020); both MH (30 +/- 26 mmHg; P < 0.05) and L-NAME (27 +/- 22 mmHg; P < 0.01) significantly increased MAP in the SCI group, but not in the AB group. There was a significant visit by time interaction for MFV suggesting an increase from predrug to postdrug following L-NAME (6 +/- 8 cm/sec; P < 0.05) and MH (4 +/- 7 cm/sec; P < 0.05), regardless of study group, with little change following ND (3 +/- 3 cm/sec). The relationship between change in MAP and MFV was significant in the SCI group following administration of MH (r(2) = 0.38; P < 0.05) and L-NAME (r(2) = 0.32; P < 0.05). These antihypotensive agents, at the doses tested, raised MAP, which was associated with an increase MFV during cognitive activation in hypotensive subjects with SCI. PMID- 26869681 TI - Isolated neonatal rat papillary muscles: a new model to translate neonatal rat myocyte signaling into contractile mechanics. AB - Isolated cardiac tissue allows investigators to study mechanisms underlying normal and pathological conditions, which would otherwise be difficult or impossible to perform in vivo. Cultured neonatal rat ventricular cardiac myocytes (NRVM) are widely used to study signaling and growth mechanisms in the heart, primarily due to the versatility, economy, and convenience of this in vitro model. However, the lack of a well-defined longitudinal cellular axis greatly hampers the ability to measure contractile function in these cells, and therefore to associate signaling with mechanical function. In these methods, we demonstrate that this limitation can be overcome by using papillary muscles isolated from neonatal rat hearts. In the methods we describe procedures for isolation of right ventricular papillary muscles from 3-day-old neonatal rats and effects of mechanical and humoral stimuli on contraction and relaxation properties of these tissues. PMID- 26869682 TI - Modulation of gamma and alpha spinal motor neurons activity by trans-spinal direct current stimulation: effects on reflexive actions and locomotor activity. AB - Spontaneous and evoked spinal activities interact to set the characteristics of emergent motor responses. Gamma motor neurons have feedforward and feedback functions in motor control, which are crucial for transforming motor commands into action. Meanwhile, the intrinsic excitability and functional connectivity of alpha motor neurons determine the accuracy of actions. In this study, we investigated the effects of trans-spinal direct current stimulation (tsDCS) on spontaneous and cortically evoked activity of well-isolated single units of gamma and alpha motor neurons in mice. We also investigated the effects of tsDCS on reflexive and locomotor actions. In general, motor neurons showed increased responses to cathodal tsDCS (c-tsDCS) and decreased responses to anodal tsDCS (a tsDCS). These effects were observed for cortically evoked discharges and spontaneous firing rates of gamma motor neurons, cortically evoked discharges of larger alpha motor neurons, and spontaneous firing rates of smaller alpha motor neurons. An exception was that spontaneous firing rates of larger alpha motor neurons showed the opposite pattern of reduction by c-tsDCS and increase by a tsDCS. Reflexive and voluntary behavior were also increased by c-tsDCS and reduced by a-tsDCS. Specifically, the amplitude and duration of crossed and tail pinch reflexes in decerebrate animals and the quality of ground and treadmill walking patterns in healthy awake animals showed this pattern. These polarity specific changes in behavior could be attributed to polarity-mediated modulation of alpha and gamma motor neuron activity and spinal circuitry. The results reveal an important principle: effects of tsDCS on spinal motor neurons depend on current polarity and cell size. PMID- 26869683 TI - PGC-1alpha promotes exercise-induced autophagy in mouse skeletal muscle. AB - Recent evidence suggests that exercise stimulates the degradation of cellular components in skeletal muscle through activation of autophagy, but the time course of the autophagy response during recovery from exercise has not been determined. Furthermore, the regulatory mechanisms behind exercise-induced autophagy remain unclear, although the muscle oxidative phenotype has been linked with basal autophagy levels. Therefore, the aim of this study was to investigate the role of the key regulator of muscle oxidative capacity, PGC-1alpha, in exercise-induced autophagy at several time points during recovery. Mice with transgenic muscle-specific overexpression (TG) or knockout (MKO) of PGC-1alpha and their respective littermate controls were subjected to a single 1 h bout of treadmill running and euthanized immediately (0 h), 2, 6, and 10 h after exercise. In the PGC-1alpha MKO strain, quadriceps protein content of the autophagy marker LC3II was increased from 2 h into recovery in lox/lox control, but not in MKO mice. In the PGC-1alpha TG strain, quadriceps protein content of LC3II was increased from 2 h after exercise in TG, but not in WT. Although AMPK and ACC phosphorylation was increased immediately following exercise, the observed exercise-induced autophagy response was not associated with phosphorylation of the AMPK-target ULK1. However, lower protein carbonyl content was observed in lox/lox and TG mice after exercise coinciding with the increased LC3 lipidation. In conclusion, the present results suggest a role of skeletal muscle PGC-1alpha in coordinating several exercise-induced adaptive responses including autophagic removal of damaged cellular components. PMID- 26869684 TI - Piezo1 haploinsufficiency does not alter mechanotransduction in mouse cochlear outer hair cells. AB - The mechanoelectrical transducer (MET) channels located at the stereocilia tip of cochlear hair cells are crucial to convert the mechanical energy of sound into receptor potentials, but the identity of its pore-forming subunits remains uncertain. Piezo1, which has been identified in the transcriptome of mammalian cochlear hair cells, encodes a transmembrane protein that forms mechanosensitive channels in other tissues. We investigated the properties of the MET channel in outer hair cells (OHCs) of Piezo1 mice (postnatal day 6-9). The MET current was elicited by deflecting the hair bundle of OHCs using sinewave and step stimuli from a piezo-driven fluid jet. Apical and basal OHCs were investigated because the properties of the MET channel vary along the cochlea. We found that the maximal MET current amplitude and the resting open probability of the MET channel in OHCs were similar between Piezo1(+/-) haploinsufficient mice and wild-type littermates. The sensitivity to block by the permeant MET channel blocker dihydrostreptomycin was also similar between the two genotypes. Finally, the anomalous mechano-gated current, which is activated by sheer force and which is tip-link independent, was unaffected in OHCs from Piezo1(+/-) haploinsufficient mice. Our results suggest that Piezo1 is unlikely to be a component of the MET channel complex in mammalian cochlear OHCs. PMID- 26869685 TI - The effects of group and single housing and automated animal monitoring on urinary corticosterone levels in male C57BL/6 mice. AB - Mice are used extensively in physiological research. Automated home-cage systems have been developed to study single-housed animals. Increased stress by different housing conditions might affect greatly the results when investigating metabolic responses. Urinary corticosteroid concentration is considered as a stress marker. The aim of the study was to compare the effects of different housing conditions and an automated home-cage system with indirect calorimetry located in an environmental chamber on corticosterone levels in mice. Male mice were housed in different conditions and in automated home-cage system to evaluate the effects of housing and measuring conditions on urine corticosterone levels. Corticosterone levels in single-housed mice in the laboratory animal center were consistently lower compared with the group-housed mice. Single-housed mice in a separate, small animal unit showed a rise in their corticosterone levels a day after they were separated to their individual cages, which decreased during the following 2 days. The corticosterone levels of group-housed mice in the same unit were increased during the first 7 days and then decreased. On day 7, the corticosterone concentrations of group-housed mice were significantly higher compared with that of single-housed mice, including the metabolic measurement protocol. In conclusion, single housing caused less stress when compared with group-housed mice. In addition, the urine corticosterone levels were decreased in single-housed mice before the metabolic measurement started. Thus, stress does not affect the results when utilizing the automated system for measuring metabolic parameters like food and water intake and calorimetry. PMID- 26869686 TI - Exercise training and alpha1-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle. AB - Exercise training (ET) increases sympathetic vasoconstrictor responsiveness and enhances contraction-mediated inhibition of sympathetic vasoconstriction (i.e., sympatholysis) through a nitric oxide (NO)-dependent mechanism. Changes in alpha2 adrenoreceptor vasoconstriction mediate a portion of these training adaptations, however the contribution of other postsynaptic receptors remains to be determined. Therefore, the purpose of this study was to investigate the effect of ET on alpha1-adrenoreceptor-mediated vasoconstriction in resting and contracting muscle. It was hypothesized that alpha1-adrenoreceptor-mediated sympatholysis would be enhanced following ET. Male Sprague Dawley rats were randomized to sedentary (S; n = 12) or heavy-intensity treadmill ET (n = 11) groups. Subsequently, rats were anesthetized and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance (FVC) at rest and during muscle contraction. The percentage change in FVC in response to sympathetic stimulation was measured in control, alpha1-adrenoreceptor blockade (Prazosin; 20 MUg, IV), and combined alpha1 and NO synthase (NOS) blockade (l NAME; 5 mg.kg(-1) IV) conditions. Sympathetic vasoconstrictor responsiveness was increased (P < 0.05) in ET compared to S rats at low, but not high (P > 0.05) stimulation frequencies at rest (S: 2 Hz: -25 +/- 4%; 5 Hz: -45 +/- 5 %; ET: 2 Hz: -35 +/- 7%, 5 Hz: -52 +/- 7%), whereas sympathetic vasoconstrictor responsiveness was not different (P > 0.05) between groups during contraction (S: 2 Hz: -11 +/- 8%; 5 Hz: -26 +/- 11%; ET: 2 Hz: -10 +/- 7%, 5 Hz: -27 +/- 12%). Prazosin blunted (P < 0.05) vasoconstrictor responsiveness in S and ET rats at rest and during contraction, and abolished group differences in vasoconstrictor responsiveness. Subsequent NOS blockade increased vasoconstrictor responses (P < 0.05) in S at rest and during contraction, whereas in ET vasoconstriction was increased (P < 0.05) in response to sympathetic stimulation at 2 Hz at rest and unchanged (P > 0.05) during contraction. ET enhanced (P < 0.05) sympatholysis, however the training-mediated improvements in sympatholysis were abolished by alpha1-adrenoreceptor blockade. Subsequent NOS inhibition did not alter (P > 0.05) sympatholysis in S or ET rats. In conclusion, ET augmented alpha1 adrenoreceptor-mediated vasoconstriction in resting skeletal muscle and enhanced alpha1-adrenoreceptor-mediated sympatholysis. Furthermore, these data suggest that NO is not required to inhibit alpha2-adrenoreceptor- and nonadrenoreceptor mediated vasoconstriction during exercise. PMID- 26869687 TI - Human atrial fibroblasts and their contribution to supraventricular arrhythmia. PMID- 26869688 TI - Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli. AB - OBJECTIVES: The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use of carbapenems, the group of beta-lactams with the broadest spectrum of activity. Bacterial resistance to carbapenems is mainly due to acquired carbapenemases or a combination of ESBL production and reduced drug influx via loss of outer-membrane porins. Here, we have studied the development of carbapenem resistance in Escherichia coli in the absence of beta-lactamases. METHODS: We selected mutants with high-level carbapenem resistance through repeated serial passage in the presence of increasing concentrations of meropenem or ertapenem for ~60 generations. Isolated clones were whole-genome sequenced, and the order in which the identified mutations arose was determined in the passaged populations. Key mutations were reconstructed, and bacterial growth rates of populations and isolated clones and resistance levels to 23 antibiotics were measured. RESULTS: High-level resistance to carbapenems resulted from a combination of downstream effects of envZ mutation and target mutations in AcrAB TolC-mediated drug export, together with PBP genes [mrdA (PBP2) after meropenem exposure or ftsI (PBP3) after ertapenem exposure]. CONCLUSIONS: Our results show that antibiotic resistance evolution can occur via several parallel pathways and that new mechanisms may appear after the most common pathways (i.e. beta lactamases and loss of porins) have been eliminated. These findings suggest that strategies to target the most commonly observed resistance mechanisms might be hampered by the appearance of previously unknown parallel pathways to resistance. PMID- 26869689 TI - Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies. AB - OBJECTIVES: The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. METHODS: Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. RESULTS: Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. CONCLUSIONS: Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds. PMID- 26869690 TI - Plasma and intracellular ribavirin concentrations are not significantly altered by abacavir in hepatitis C virus-infected patients. AB - OBJECTIVES: The objective of this study was to evaluate the effects of abacavir on intracellular ribavirin triphosphate and plasma ribavirin trough concentrations. METHODS: Hepatitis C virus-infected subjects who had been cured or failed prior treatment were randomized to 8 weeks of ribavirin alone (N = 14; weight-based dosing) or weight-based ribavirin + abacavir (N = 14; 300 mg orally every 12 h). Ribavirin trough concentrations were measured on days 14, 28, 42 and 56; PBMCs for ribavirin triphosphate determination were sampled on days 28 and 56, pre-dose and at 6 and 12 h post-dose. ClinicalTrials.gov: NCT01052701. RESULTS: Twenty-six subjects completed the study (24 males, 17 Caucasians, median age 52 years); 2 were excluded for missed pharmacokinetic visits. Fourteen subjects received ribavirin + abacavir and 12 received ribavirin alone. Mean +/- SD plasma ribavirin trough concentrations (MUg/mL) on days 14, 28, 42 and 56, respectively, were not significantly different with coadministration of abacavir (1.54 +/- 0.60, 1.93 +/- 0.54, 2.14 +/- 0.73 and 2.54 +/- 1.05) compared with ribavirin alone (1.48 +/- 0.32, 2.08 +/- 0.41, 2.32 +/- 0.47 and 2.60 +/- 0.62) (P > 0.40). Mean ribavirin triphosphate intracellular concentrations (pmol/10(6) cells) on days 28 and 56, respectively, did not differ statistically between abacavir users (11.98 +/- 9.86 and 15.87 +/- 12.52) and non-users (15.91 +/- 15.58 and 15.93 +/- 12.69) (P > 0.4). Adverse events were mild or moderate, except for three grade 3 occurrences of transaminitis, cholecystitis and low absolute neutrophil count that resolved and were judged not attributable to study medications. CONCLUSIONS: Abacavir did not significantly alter ribavirin or ribavirin triphosphate concentrations. PMID- 26869691 TI - Toxin B PCR cycle threshold as a predictor of poor outcome of Clostridium difficile infection: a derivation and validation cohort study. AB - OBJECTIVES: Prediction of patients with poor outcome is necessary in order to plan the proper management of Clostridium difficile infection (CDI); however, clinical criteria are insufficient. In a previous study, we observed that high toxigenic C. difficile cfu stool counts at diagnosis were associated with a poor outcome. Our objective was to investigate the role of the PCR toxin B amplification cycle threshold (Ct) in the prediction of CDI poor outcome and to derive and validate a high-risk prediction rule using this marker. METHODS: We prospectively included patients with CDI (derivation cohort, January 2013 to June 2014; and validation cohort, December 2014 to May 2015), who were followed for at least 2 months after their last episode/recurrence. All samples were tested with XpertTM C. difficile. RESULTS: For the derivation cohort (n = 129) toxin B Ct was independently associated with poor outcome (P < 0.001). The receiver operating characteristic (ROC) curve yielded an AUC of 0.816. Using a cut-off of <23.5 cycles for high risk of poor outcome, the diagnostic accuracy was 81.4%, the sensitivity was 46.5% (95% CI 32.5-61.1) and the specificity was 98.8% (95% CI 93.7-99.8). For the validation cohort (n = 170), the diagnostic accuracy was 81.8%, the sensitivity was 88.4% (95% CI 75.5-94.9) and the specificity was 79.5% (95% CI 71.7-85.6). The ROC curve yielded an AUC of 0.857. CONCLUSIONS: Low toxin B Ct values from samples collected at the initial moment of diagnosis appears to be a strong marker for poor outcome. This available test may identify, at an early stage, patients who are at higher risk of a poor outcome CDI. PMID- 26869692 TI - Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements. AB - OBJECTIVES: This multicentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters. PATIENTS AND METHODS: Nineteen patients with MODS and CVVHDF receiving piperacillin/tazobactam were enrolled from three tertiary hospitals (95 plasma samples). Population PK modelling and Monte Carlo simulations were performed using NONMEM v7.3((r)). RESULTS: Patients' median age was 70 years (range 39-82), median weight was 80 kg (45-129), median APACHE II score at admission was 21 (13-33) and median SOFA score on the day of study was 11 (8-21). The final population PK model was characterized by CL (L/h) = 6.11 * [weight (kg)/80](1.39) * CLMEMB. If membrane = 1.5 m(2) AN69ST, CLMEMB = 1; if membrane = 0.9 m(2) AN69, CLMEMB = 0.51. Monte Carlo simulations showed that: (i) to maintain unbound piperacillin concentrations above the MIC for the bacteria for 100% of dosing interval T (100%fuT>MIC), patients receiving CVVHDF with 1.5 m(2) AN69ST membranes required doses of 4000 mg q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8-16 mg/L) (2000 mg q8h was sufficient for patients with CVVHDF using 0.9 m(2) AN69 membranes); and (ii) for the treatment of bacteria with high susceptibility to piperacillin (MIC <4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight. CONCLUSIONS: Our results suggest that type of membrane and body weight should be considered for piperacillin dose titration in critically ill patients with MODS and CVVHDF requirement. PMID- 26869694 TI - Pharmacy workers' knowledge and provision of medication for termination of pregnancy in Kenya. AB - OBJECTIVE: To assess pharmacy workers' knowledge and provision of abortion information and methods in Kenya. METHODS: In 2013 we interviewed 235 pharmacy workers in Nairobi, Mombasa and Kisumu about the medical abortion services they provide. We also used mystery clients, who made 401 visits to pharmacies to collect first-hand information on abortion practices. RESULTS: The majority (87.5%) of pharmacy workers had heard of misoprostol but only 39.2% had heard of mifepristone. We found that pharmacy workers had limited knowledge of correct medical abortion regimens, side effects and complications and the legal status of abortion drugs. 49.8% of pharmacy workers reported providing abortion information to clients and 4.3% reported providing abortion methods. 75.2% of pharmacies referred mystery clients to another provider, though 64.2% of pharmacies advised mystery clients to continue with their pregnancy. Pharmacy workers reported that they were experiencing demand for abortion services from clients. CONCLUSIONS: Pharmacy workers are important providers of information and referrals for women seeking abortion, however their medical abortion knowledge is limited. Training pharmacy workers on medical abortion may improve the quality of information provided and access to safe abortion. PMID- 26869693 TI - Implementation of antimicrobial stewardship interventions recommended by national toolkits in primary and secondary healthcare sectors in England: TARGET and Start Smart Then Focus. AB - OBJECTIVES: To assess and compare the implementation of antimicrobial stewardship (AMS) interventions recommended within the national AMS toolkits, TARGET and Start Smart Then Focus, in English primary and secondary healthcare settings in 2014, to determine the prevalence of cross-sector engagement to drive AMS interventions and to propose next steps to improve implementation of AMS. METHODS: Electronic surveys were circulated to all 211 clinical commissioning groups (CCGs; primary sector) and to 146 (out of the 159) acute trusts (secondary sector) in England. Response rates were 39% and 63% for the primary and secondary sectors, respectively. RESULTS: The majority of CCGs and acute trusts reported reviewing national AMS toolkits formally or informally (60% and 87%, respectively). However, only 13% of CCGs and 46% of acute trusts had developed an action plan for the implementation of these toolkits. Only 5% of CCGs had antimicrobial pharmacists in post; however, the role of specialist antimicrobial pharmacists continued to remain embedded within acute trusts, with 83% of responding trusts having an antimicrobial pharmacist at a senior grade. CONCLUSIONS: The majority of healthcare organizations review national AMS toolkits; however, implementation of the toolkits, through the development of action plans to deliver AMS interventions, requires improvement. For the first time, we report the extent of cross-sector and multidisciplinary collaboration to deliver AMS interventions in both primary and secondary care sectors in England. Results highlight that further qualitative and quantitative work is required to explore mutual benefits and promote best practice. Antimicrobial pharmacists remain leaders for implementing AMS interventions across both primary and secondary healthcare sectors. PMID- 26869695 TI - Socioeconomic inequalities in injuries treated in primary care in Madrid, Spain. AB - Background: Socioeconomic inequalities in injury morbidity are an important yet understudied issue in Southern Europe. This study analysed the injuries treated in primary care in the Community of Madrid, Spain, by socioeconomic status (SES), sex and age. Methods: This was a cross-sectional study of injuries registered in the primary care electronic medical records of the Madrid Health Service in 2012. Incidence stratified by sex, SES and type of injury were calculated. Poisson regression was performed. Results: A statistically significant upward trend in global injury incidence was observed with decreasing SES in all age groups. By type of injury, the largest differences were observed in injuries by foreign body in men aged 15-44 and in poisonings in girls under 15 years of age. Burns risk also stood out in the group of girls under 15 years of age with the lowest SES. In the group above 74 years of age, wounds, bruises and sprains had the lowest SES differences in both sexes, and the risk of fractures was lower in the most socioeconomically advantaged group. Conclusion: People with lower SES were at a greater risk of injury. The relationship between SES and injury varies by type of injury and age. PMID- 26869698 TI - The Plant Cell Reviews Small RNA and Chromatin Dynamics: From Small Genetic Circuits to Complex Genomes. PMID- 26869697 TI - The First Rule of Plant Transposable Element Silencing: Location, Location, Location. AB - Transposable elements (TEs) are mobile units of DNA that comprise large portions of plant genomes. Besides creating mutations via transposition and contributing to genome size, TEs play key roles in chromosome architecture and gene regulation. TE activity is repressed by overlapping mechanisms of chromatin condensation, epigenetic transcriptional silencing, and targeting by small interfering RNAs. The specific regulation of different TEs, as well as their different roles in chromosome architecture and gene regulation, is specified by where on the chromosome the TE is located: near a gene, within a gene, in a pericentromere/TE island, or at the centromere core. In this Review, we investigate the silencing mechanisms responsible for inhibiting TE activity for each of these chromosomal contexts, emphasizing that chromosomal location is the first rule dictating the specific regulation of each TE. PMID- 26869699 TI - RNAi in Plants: An Argonaute-Centered View. AB - Argonaute (AGO) family proteins are effectors of RNAi in eukaryotes. AGOs bind small RNAs and use them as guides to silence target genes or transposable elements at the transcriptional or posttranscriptional level. Eukaryotic AGO proteins share common structural and biochemical properties and function through conserved core mechanisms in RNAi pathways, yet plant AGOs have evolved specialized and diversified functions. This Review covers the general features of AGO proteins and highlights recent progress toward our understanding of the mechanisms and functions of plant AGOs. PMID- 26869701 TI - Creating Order from Chaos: Epigenome Dynamics in Plants with Complex Genomes. AB - Flowering plants have strikingly distinct genomes, although they contain a similar suite of expressed genes. The diversity of genome structures and organization is largely due to variation in transposable elements (TEs) and whole genome duplication (WGD) events. We review evidence that chromatin modifications and epigenetic regulation are intimately associated with TEs and likely play a role in mediating the effects of WGDs. We hypothesize that the current structure of a genome is the result of various TE bursts and WGDs and it is likely that the silencing mechanisms and the chromatin structure of a genome have been shaped by these events. This suggests that the specific mechanisms targeting chromatin modifications and epigenomic patterns may vary among different species. Many crop species have likely evolved chromatin-based mechanisms to tolerate silenced TEs near actively expressed genes. These interactions of heterochromatin and euchromatin are likely to have important roles in modulating gene expression and variability within species. PMID- 26869703 TI - SUMO Is a Critical Regulator of Salt Stress Responses in Rice. AB - SUMO (Small Ubiquitin-like Modifier) conjugation onto target proteins has emerged as a very influential class of protein modification systems. SUMO1/2 double mutant plants are nonviable, underlining the importance of SUMO conjugation to plant survival. Once covalently bound, SUMO can alter a conjugated protein's stability and/or function. SUMO conjugation is a highly dynamic process that can be rapidly reversed by the action of SUMO proteases. The balance between the conjugated/deconjugated forms is a major determinant in the modulation of SUMO target function. Despite the important mechanistic role of SUMO proteases in model plants, until now the identity or the function of these regulatory enzymes has not been defined in any crop plant. In this report, we reveal the ubiquitin like protease class of SUMO protease gene family in rice (Oryza sativa) and demonstrate a critical role for OsOTS1 SUMO protease in salt stress. OsOTS-RNAi rice plants accumulate high levels of SUMO-conjugated proteins during salt stress and are highly salt sensitive; however, in non-salt conditions, they are developmentally indistinguishable from wild-type plants. Transgenic rice plants overexpressing OsOTS1 have increased salt tolerance and a concomitant reduction in the levels of SUMOylated proteins. We demonstrate that OsOTS1 confers salt tolerance in rice by increasing root biomass. High salinity triggers OsOTS1 degradation, indicating that increased SUMO conjugation in rice plants during salt stress is in part achieved by down-regulation of OTS1/2 activity. OsOTS1 is nuclear localized indicating a direct requirement of OsOTS1-dependent deSUMOylation activity in rice nuclei for salt tolerance. PMID- 26869702 TI - expVIP: a Customizable RNA-seq Data Analysis and Visualization Platform. AB - The majority of transcriptome sequencing (RNA-seq) expression studies in plants remain underutilized and inaccessible due to the use of disparate transcriptome references and the lack of skills and resources to analyze and visualize these data. We have developed expVIP, an expression visualization and integration platform, which allows easy analysis of RNA-seq data combined with an intuitive and interactive interface. Users can analyze public and user-specified data sets with minimal bioinformatics knowledge using the expVIP virtual machine. This generates a custom Web browser to visualize, sort, and filter the RNA-seq data and provides outputs for differential gene expression analysis. We demonstrate expVIP's suitability for polyploid crops and evaluate its performance across a range of biologically relevant scenarios. To exemplify its use in crop research, we developed a flexible wheat (Triticum aestivum) expression browser (www.wheat expression.com) that can be expanded with user-generated data in a local virtual machine environment. The open-access expVIP platform will facilitate the analysis of gene expression data from a wide variety of species by enabling the easy integration, visualization, and comparison of RNA-seq data across experiments. PMID- 26869700 TI - Small Genetic Circuits and MicroRNAs: Big Players in Polymerase II Transcriptional Control in Plants. AB - RNA Polymerase II (Pol II) regulatory cascades involving transcription factors (TFs) and their targets orchestrate the genetic circuitry of every eukaryotic organism. In order to understand how these cascades function, they can be dissected into small genetic networks, each containing just a few Pol II transcribed genes, that generate specific signal-processing outcomes. Small RNA regulatory circuits involve direct regulation of a small RNA by a TF and/or direct regulation of a TF by a small RNA and have been shown to play unique roles in many organisms. Here, we will focus on small RNA regulatory circuits containing Pol II transcribed microRNAs (miRNAs). While the role of miRNA containing regulatory circuits as modular building blocks for the function of complex networks has long been on the forefront of studies in the animal kingdom, plant studies are poised to take a lead role in this area because of their advantages in probing transcriptional and posttranscriptional control of Pol II genes. The relative simplicity of tissue- and cell-type organization, miRNA targeting, and genomic structure make the Arabidopsis thaliana plant model uniquely amenable for small RNA regulatory circuit studies in a multicellular organism. In this Review, we cover analysis, tools, and validation methods for probing the component interactions in miRNA-containing regulatory circuits. We then review the important roles that plant miRNAs are playing in these circuits and summarize methods for the identification of small genetic circuits that strongly influence plant function. We conclude by noting areas of opportunity where new plant studies are imminently needed. PMID- 26869706 TI - Common mechanisms for the adaptive responses to exercise and heat stress. PMID- 26869704 TI - The Thioredoxin GbNRX1 Plays a Crucial Role in Homeostasis of Apoplastic Reactive Oxygen Species in Response to Verticillium dahliae Infection in Cotton. AB - Examining the proteins that plants secrete into the apoplast in response to pathogen attack provides crucial information for understanding the molecular mechanisms underlying plant innate immunity. In this study, we analyzed the changes in the root apoplast secretome of the Verticillium wilt-resistant island cotton cv Hai 7124 (Gossypium barbadense) upon infection with Verticillium dahliae Two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry analysis identified 68 significantly altered spots, corresponding to 49 different proteins. Gene ontology annotation indicated that most of these proteins function in reactive oxygen species (ROS) metabolism and defense response. Of the ROS related proteins identified, we further characterized a thioredoxin, GbNRX1, which increased in abundance in response to V. dahliae challenge, finding that GbNRX1 functions in apoplastic ROS scavenging after the ROS burst that occurs upon recognition of V. dahliae Silencing of GbNRX1 resulted in defective dissipation of apoplastic ROS, which led to higher ROS accumulation in protoplasts. As a result, the GbNRX1-silenced plants showed reduced wilt resistance, indicating that the initial defense response in the root apoplast requires the antioxidant activity of GbNRX1. Together, our results demonstrate that apoplastic ROS generation and scavenging occur in tandem in response to pathogen attack; also, the rapid balancing of redox to maintain homeostasis after the ROS burst, which involves GbNRX1, is critical for the apoplastic immune response. PMID- 26869707 TI - Increased ventilatory variability and complexity in patients with hyperventilation disorder. AB - It has been hypothesized that hyperventilation disorders could be characterized by an abnormal ventilatory control leading to enhanced variability of resting ventilation. The variability of tidal volume (VT) often depicts a nonnormal distribution that can be described by the negative slope characterizing augmented breaths formed by the relationship between the probability density distribution of VT and VT on a log-log scale. The objectives of this study were to describe the variability of resting ventilation [coefficient of variation (CV) of VT and slope], the stability in respiratory control (loop, controller and plant gains characterizing ventilatory-chemoresponsiveness interactions) and the chaotic-like dynamics (embedding dimension, Kappa values characterizing complexity) of resting ventilation in patients with a well-defined dysfunctional breathing pattern characterized by air hunger and constantly decreased PaCO2 during a cardiopulmonary exercise test. Compared with 14 healthy subjects with similar anthropometrics, 23 patients with hyperventilation were characterized by increased variability of resting tidal ventilation (CV of VT median [interquartile]: 26% [19-35] vs. 36% [28-48], P = 0.020; slope: -6.63 [-7.65; 5.36] vs. -3.88 [-5.91; -2.66], P = 0.004) that was not related to increased chemical drive (loop gain: 0.051 [0.039-0.221] vs. 0.044 [0.012-0.087], P = 0.149) but that was related to an increased ventilatory complexity (Kappa values, P < 0.05). Plant gain was decreased in patients and correlated with complexity (with Kappa 5 - degree 5: Rho = -0.48, P = 0.006). In conclusion, well-defined patients suffering from hyperventilation disorder are characterized by increased variability of their resting ventilation due to increased ventilatory complexity with stable ventilatory-chemoresponsiveness interactions. PMID- 26869708 TI - High-phosphorus diet maximizes and low-dose calcitriol attenuates skeletal muscle changes in long-term uremic rats. AB - Although disorders of mineral metabolism and skeletal muscle are common in chronic kidney disease (CKD), their potential relationship remains unexplored. Elevations in plasma phosphate, parathyroid hormone, and fibroblastic growth factor 23 together with decreased calcitriol levels are common features of CKD. High-phosphate intake is a major contributor to progression of CKD. This study was primarily aimed to determine the influence of high-phosphate intake on muscle and to investigate whether calcitriol supplementation counteracts negative skeletal muscle changes associated with long-term uremia. Proportions and metabolic and morphological features of myosin-based muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of uremic rats (5/6 nephrectomy, Nx) and compared with sham-operated (So) controls. Three groups of Nx rats received either a standard diet (0.6% phosphorus, Nx-Sd), or a high-phosphorus diet (0.9% phosphorus, Nx-Pho), or a high-phosphorus diet plus calcitriol (10 ng/kg 3 day/wk ip, Nx-Pho + Cal) for 12 wk. Two groups of So rats received either a standard diet or a high-phosphorus diet (So-Pho) over the same period. A multivariate analysis encompassing all fiber-type characteristics indicated that Nx-Pho + Cal rats displayed skeletal muscle phenotypes intermediate between Nx-Pho and So-Pho rats and that uremia induced skeletal muscle changes were of greater magnitude in Nx-Pho than in Nx-Sd rats. In uremic rats, treatment with calcitriol preserved fiber-type composition, cross-sectional size, myonuclear domain size, oxidative capacity, and capillarity of muscle fibers. These data demonstrate that a high-phosphorus diet potentiates and low-dose calcitriol attenuates adverse skeletal muscle changes in long-term uremic rats. PMID- 26869705 TI - Genome-Wide Association Mapping and Genomic Prediction Elucidate the Genetic Architecture of Morphological Traits in Arabidopsis. AB - Quantitative traits in plants are controlled by a large number of genes and their interaction with the environment. To disentangle the genetic architecture of such traits, natural variation within species can be explored by studying genotype phenotype relationships. Genome-wide association studies that link phenotypes to thousands of single nucleotide polymorphism markers are nowadays common practice for such analyses. In many cases, however, the identified individual loci cannot fully explain the heritability estimates, suggesting missing heritability. We analyzed 349 Arabidopsis accessions and found extensive variation and high heritabilities for different morphological traits. The number of significant genome-wide associations was, however, very low. The application of genomic prediction models that take into account the effects of all individual loci may greatly enhance the elucidation of the genetic architecture of quantitative traits in plants. Here, genomic prediction models revealed different genetic architectures for the morphological traits. Integrating genomic prediction and association mapping enabled the assignment of many plausible candidate genes explaining the observed variation. These genes were analyzed for functional and sequence diversity, and good indications that natural allelic variation in many of these genes contributes to phenotypic variation were obtained. For ACS11, an ethylene biosynthesis gene, haplotype differences explaining variation in the ratio of petiole and leaf length could be identified. PMID- 26869709 TI - Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study. AB - Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 +/- 1.7% vs. 6.8 +/- 1.3%; values are means +/- SD). In terms of PLM, baseline LBF (196 +/- 33 ml/min vs. 328 +/- 20 ml/min), peak change in LBF from baseline (133 +/- 28 ml/min vs. 483 +/- 86 ml/min), and the LBF area under the curve (16 +/- 8.3 vs. 143 +/- 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis. PMID- 26869710 TI - Analogs of microgravity: head-down tilt and water immersion. AB - This article briefly reviews the fidelity of ground-based methods used to simulate human existence in weightlessness (spaceflight). These methods include horizontal bed rest (BR), head-down tilt bed rest (HDT), head-out water immersion (WI), and head-out dry immersion (DI; immersion with an impermeable elastic cloth barrier between subject and water). Among these, HDT has become by far the most commonly used method, especially for longer studies. DI is less common but well accepted for long-duration studies. Very few studies exist that attempt to validate a specific simulation mode against actual microgravity. Many fundamental physical, and thus physiological, differences exist between microgravity and our methods to simulate it, and between the different methods. Also, although weightlessness is the salient feature of spaceflight, several ancillary factors of space travel complicate Earth-based simulation. In spite of these discrepancies and complications, the analogs duplicate many responses to 0 G reasonably well. As we learn more about responses to microgravity and spaceflight, investigators will continue to fine-tune simulation methods to optimize accuracy and applicability. PMID- 26869711 TI - Hindlimb unloading: rodent analog for microgravity. AB - The rodent hindlimb unloading (HU) model was developed in the 1980s to make it possible to study mechanisms, responses, and treatments for the adverse consequences of spaceflight. Decades before development of the HU model, weightlessness was predicted to yield deficits in the principal tissues responsible for structure and movement on Earth, primarily muscle and bone. Indeed, results from early spaceflight and HU experiments confirmed the expected sensitivity of the musculoskeletal system to gravity loading. Results from human and animal spaceflight and HU experiments show that nearly all organ systems and tissues studied display some measurable changes, albeit sometimes minor and of uncertain relevance to astronaut health. The focus of this review is to examine key HU results for various organ systems including those related to stress; the immune, cardiovascular, and nervous systems; vision changes; and wound healing. Analysis of the validity of the HU model is important given its potential value for both hypothesis testing and countermeasure development. PMID- 26869712 TI - Hypercapnia is more important than hypoxia in the neuro-outcomes of sleep disordered breathing. PMID- 26869713 TI - Chronic central serotonin depletion attenuates ventilation and body temperature in young but not adult Tph2 knockout rats. AB - Genetic deletion of brain serotonin (5-HT) neurons in mice leads to ventilatory deficits and increased neonatal mortality during development. However, it is unclear if the loss of the 5-HT neurons or the loss of the neurochemical 5-HT led to the observed physiologic deficits. Herein, we generated a mutant rat model with constitutive central nervous system (CNS) 5-HT depletion by mutation of the tryptophan hydroxylase 2 (Tph2) gene in dark agouti (DA(Tph2-/-)) rats. DA(Tph2-/ ) rats lacked TPH immunoreactivity and brain 5-HT but retain dopa decarboxylase expressing raphe neurons. Mutant rats were also smaller, had relatively high mortality (~50%), and compared with controls had reduced room air ventilation and body temperatures at specific postnatal ages. In adult rats, breathing at rest and hypoxic and hypercapnic chemoreflexes were unaltered in adult male and female DA(Tph2-/-) rats. Body temperature was also maintained in adult DA(Tph2-/-) rats exposed to 4 degrees C, indicating unaltered ventilatory and/or thermoregulatory control mechanisms. Finally, DA(Tph2-/-) rats treated with the 5-HT precursor 5 hydroxytryptophan (5-HTP) partially restored CNS 5-HT and showed increased ventilation (P < 0.05) at a developmental age when it was otherwise attenuated in the mutants. We conclude that constitutive CNS production of 5-HT is critically important to fundamental homeostatic control systems for breathing and temperature during postnatal development in the rat. PMID- 26869715 TI - Improved Chiral Separation of Methamphetamine Enantiomers Using CSP-LC-MS-MS. AB - To determine the true enantiomeric composition of methamphetamine urine drug testing results, chiral separation of dextro (D) and levo (L) enantiomers is necessary. While enantiomeric separation of methamphetamine has traditionally been accomplished using gas chromatography-mass spectrometry (GC-MS), chiral separation of D- and L-methamphetamine by chiral stationary phase (CSP) liquid chromatography-mass spectrometry/mass spectrometry (LC-MS-MS) has proved more reliable. Chirally selective detection of methamphetamine by GC-MS is often performed using L-N-trifluoroacetyl-prolyl chloride (TPC). L-TPC, a chiral compound, is known to have impurities that can affect the chiral composition percentages of the methamphetamine sample, potentially leading to inaccurate patient results. The comparative analysis of the samples run by GC and LC methods showed preferential bias of the GC method for producing error rates, consistent with previous research, of 8-19%. The CSP-LC-MS-MS method produces percent deviation errors of <2%. Additionally, the GC method failed to produce results that were 100% D- or L-isomer even for enantiomerically pure standards. A higher rate of D- and L-methamphetamine isomer racemization is seen in samples when analyzed by GC-MS using L-TPC-derivatizing agent. This racemization is not seen when these samples are tested with CSP-LC-MS-MS. Thus, a more accurate method of enantiomeric analysis is provided by CSP-LC-MS-MS. PMID- 26869714 TI - Cytosolic calcium transients are a determinant of contraction-induced HSP72 transcription in single skeletal muscle fibers. AB - The intrinsic activating factors that induce transcription of heat shock protein 72 (HSP72) in skeletal muscle following exercise remain unclear. We hypothesized that the cytosolic Ca(2+) transient that occurs with depolarization is a determinant. We utilized intact, single skeletal muscle fibers from Xenopus laevis to test the role of the cytosolic Ca(2+) transient and several other exercise-related factors (fatigue, hypoxia, AMP kinase, and cross-bridge cycling) on the activation of HSP72 transcription. HSP72 and HSP60 mRNA levels were assessed with real-time quantitative PCR; cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was assessed with fura-2. Both fatiguing and nonfatiguing contractions resulted in a significant increase in HSP72 mRNA. As expected, peak [Ca(2+)]cyt remained tightly coupled with peak developed tension in contracting fibers. Pretreatment with N-benzyl-p-toluene sulfonamide (BTS) resulted in depressed peak developed tension with stimulation, while peak [Ca(2+)]cyt remained largely unchanged from control values. Despite excitation-contraction uncoupling, BTS-treated fibers displayed a significant increase in HSP72 mRNA. Treatment of fibers with hypoxia (Po2: <3 mmHg) or AMP kinase activation had no effect on HSP72 mRNA levels. These results suggest that the intermittent cytosolic Ca(2+) transient that occurs with skeletal muscle depolarization provides a sufficient activating stimulus for HSP72 transcription. Metabolic or mechanical factors associated with fatigue development and cross-bridge cycling likely play a more limited role. PMID- 26869716 TI - CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. AB - The Fas/FasL (CD95/CD178) system is required for immune regulation; however, it is unclear in which cells, when, and where Fas/FasL molecules act in the immune system. We found that CD8(+)CD122(+) cells, which are mostly composed of memory T cells in comparison with naive cells in the CD8(+)CD122(-) population, were previously shown to include cells with regulatory activity and could be separated into CD49d(low) cells and CD49d(high) cells. We established in vitro and in vivo experimental systems to evaluate the regulatory activity of CD122(+) cells. Regulatory activity was observed in CD8(+)CD122(+)CD49d(low) but not in CD8(+)CD122(+)CD49d(high) cells, indicating that the regulatory cells in the CD8(+)CD122(+) population could be narrowed down to CD49d(low) cells. CD8(+)CD122(-) cells taken from lymphoproliferation (lpr) mice were resistant to regulation by normal CD122(+) Tregs. CD122(+) Tregs taken from generalized lymphoproliferative disease (gld) mice did not regulate wild-type CD8(+)CD122(-) cells, indicating that the regulation by CD122(+) Tregs is Fas/FasL-dependent. CD122(+) Tregs taken from IL-10-deficient mice could regulate CD8(+)CD122(-) cells as equally as wild-type CD122(+) Tregs both in vitro and in vivo. MHC class I-missing T cells were not regulated by CD122(+) Tregs in vitro. CD122(+) Tregs also regulated CD4(+) cells in a Fas/FasL-dependent manner in vitro. These results suggest an essential role of Fas/FasL as a terminal effector of the CD122(+) Tregs that kill activated T cells to maintain immune homeostasis. PMID- 26869718 TI - The impact of clinical maturity on competency in evidence-based medicine: a mixed methods study. AB - OBJECTIVE: To identify whether the clinical maturity of medical trainees impacts upon the level of trainee competency in evidence-based medicine (EBM). MATERIALS AND METHODS: Undergraduate and graduate-entry medical trainees entering their first year of training in the clinical environment were recruited for this study. Competency in EBM was measured using a psychometrically validated instrument. EBM competency scores were analysed using Student's t tests, in order to differentiate between undergraduate and graduate-entry trainee performance. Ten focus group discussions were conducted with undergraduate and graduate-entry trainees. Audio transcripts were thematically analysed. RESULTS: Data on a total of 885 medical trainees were collected over a 5-year period. Undergraduate trainees had significantly higher EBM competency scores during years in which the programme was presented in a didactic format (mean difference (MD)=1.24 (95% CI)CI 0.21 to 2.26; 1.78 (0.39 to 3.17); 2.13 (1.16 to 3.09)). Graduate trainee EBM competency scores increased when a blended learning approach to EBM was adopted, demonstrating no significant difference in EBM competency scores between undergraduate and graduate cohorts (-0.27 (-1.38 to 0.85); -0.39 (-1.57 to 0.79). Qualitative findings indicated that differences in learning and teaching preference among undergraduate and graduate-entry trainees influenced the level of competency obtained in EBM. CONCLUSIONS: Clinical maturity is the only one factor that may influence medical trainees' competency in EBM. Other predictors of EBM competency may include previous training and exposure to epidemiology, biostatistics and information literacy. While graduate-entry medical students may have more 'life' experience, or maturity, it does not necessarily translate into clinical maturity and integration into the clinical environment. PMID- 26869719 TI - The global reach of public health. PMID- 26869717 TI - Interaction of TAPBPR, a tapasin homolog, with MHC-I molecules promotes peptide editing. AB - Peptide loading of major histocompatibility complex class I (MHC-I) molecules is central to antigen presentation, self-tolerance, and CD8(+) T-cell activation. TAP binding protein, related (TAPBPR), a widely expressed tapasin homolog, is not part of the classical MHC-I peptide-loading complex (PLC). Using recombinant MHC I molecules, we show that TAPBPR binds HLA-A*02:01 and several other MHC-I molecules that are either peptide-free or loaded with low-affinity peptides. Fluorescence polarization experiments establish that TAPBPR augments peptide binding by MHC-I. The TAPBPR/MHC-I interaction is reversed by specific peptides, related to their affinity. Mutational and small-angle X-ray scattering (SAXS) studies confirm the structural similarities of TAPBPR with tapasin. These results support a role of TAPBPR in stabilizing peptide-receptive conformation(s) of MHC I, permitting peptide editing. PMID- 26869720 TI - Brexit: a confused concept that threatens public health. PMID- 26869721 TI - New Cochrane protocols and reviews of relevance to health promotion and public health, published in November 2015-January 2016 of The Cochrane Library. PMID- 26869722 TI - Entomological journals and publishing in Japan. AB - Here I present an overview of entomological journals and publishing in Japan, thereby providing a convenient portal to the valuable scientific resources for the world's entomological researchers and scientific communities. Currently, except for several international journals published fully in English such as Applied Entomology and Zoology and Entomological Science, many entomological and entomology-related journals in Japan are not indexed by major scientific databases like Web of Science, and therefore they are neither conveniently recognizable nor accessible for the world's entomological communities. However, I point out that many of the contents of such journals are freely available via Japan's public platforms for electronic scientific literature, Japan Science and Technology Information Aggregator, Electronic (J-stage) or Citation Information by National Institute of Informatics (CiNii). Here I list 32 entomological and entomology-related societies and their 45 journals, the majority of which belong to either the Union of Japanese Societies for Insect Sciences (UJSIS), the Union of the Japanese Societies for Systematic Biology (UJSSB), the Union of Japanese Societies for Natural History (UJSNH), or the Union of Japanese Societies for Biological Science (UJSBS), with their respective URL and open-access availability. PMID- 26869723 TI - Acoustic particle palpation for measuring tissue elasticity. AB - We propose acoustic particle palpation-the use of sound to press a population of acoustic particles against an interface-as a method for measuring the qualitative and quantitative mechanical properties of materials. We tested the feasibility of this method by emitting ultrasound pulses across a tunnel of an elastic material filled with microbubbles. Ultrasound stimulated the microbubble cloud to move in the direction of wave propagation, press against the distal surface, and cause deformations relevant for elasticity measurements. Shear waves propagated away from the palpation site with a velocity that was used to estimate the material's Young's modulus. PMID- 26869724 TI - Quantitative contrast-enhanced optical coherence tomography. AB - We have developed a model to accurately quantify the signals produced by exogenous scattering agents used for contrast-enhanced Optical Coherence Tomography (OCT). This model predicts distinct concentration-dependent signal trends that arise from the underlying physics of OCT detection. Accordingly, we show that real scattering particles can be described as simplified ideal scatterers with modified scattering intensity and concentration. The relation between OCT signal and particle concentration is approximately linear at concentrations lower than 0.8 particle per imaging voxel. However, at higher concentrations, interference effects cause signal to increase with a square root dependence on the number of particles within a voxel. Finally, high particle concentrations cause enough light attenuation to saturate the detected signal. Predictions were validated by comparison with measured OCT signals from gold nanorods (GNRs) prepared in water at concentrations ranging over five orders of magnitude (50 fM to 5 nM). In addition, we validated that our model accurately predicts the signal responses of GNRs in highly heterogeneous scattering environments including whole blood and living animals. By enabling particle quantification, this work provides a valuable tool for current and future contrast-enhanced in vivo OCT studies. More generally, the model described herein may inform the interpretation of detected signals in modalities that rely on coherence-based detection or are susceptible to interference effects. PMID- 26869725 TI - Multifunctional-layered materials for creating membrane-restricted nanodomains and nanoscale imaging. AB - Experimental platform that allows precise spatial positioning of biomolecules with an exquisite control at nanometer length scales is a valuable tool to study the molecular mechanisms of membrane bound signaling. Using micromachined thin film gold (Au) in layered architecture, it is possible to add both optical and biochemical functionalities in in vitro. Towards this goal, here, I show that docking of complementary DNA tethered giant phospholiposomes on Au surface can create membrane-restricted nanodomains. These nanodomains are critical features to dissect molecular choreography of membrane signaling complexes. The excited surface plasmon resonance modes of Au allow label-free imaging at diffraction limited resolution of stably docked DNA tethered phospholiposomes, and lipid detergent bicelle structures. Such multifunctional building block enables realizing rigorously controlled in vitro set-up to model membrane anchored biological signaling, besides serving as an optical tool for nanoscale imaging. PMID- 26869726 TI - Searching for trans ethyl methyl ether in Orion KL. AB - We report on the tentative detection of trans ethyl methyl ether (tEME), t CH3CH2OCH3, through the identification of a large number of rotational lines from each one of the spin states of the molecule towards Orion KL. We also search for gauche-trans-n-propanol, Gt-n-CH3CH2CH2OH, an isomer of tEME in the same source. We have identified lines of both species in the IRAM 30 m line survey and in the ALMA Science Verification data. We have obtained ALMA maps to establish the spatial distribution of these species. Whereas tEME mainly arises from the compact ridge component of Orion, Gt-n-propanol appears at the emission peak of ethanol (south hot core). The derived column densities of these species at the location of their emission peaks are <=(4.0 +/- 0.8) * 1015 cm-2 and <=(1.0 +/- 0.2)* 1015 cm-2 for tEME and Gt-n-propanol, respectively. The rotational temperature is ~100 K for both molecules. We also provide maps of CH3OCOH, CH3CH2OCOH, CH3OCH3, CH3OH, and CH3CH2OH to compare the distribution of these organic saturated O-bearing species containing methyl and ethyl groups in this region. Abundance ratios of related species and upper limits to the abundances of non-detected ethers are provided. We derive an abundance ratio N(CH3OCH3)/N(tEME) >= 150 in the compact ridge of Orion. PMID- 26869727 TI - Lichenized and lichenicolous fungi from the Albanian Alps (Kosovo, Montenegro). AB - 396 taxa (381 species) of lichenized and 45 species of lichenicolous fungi from the upper montane, subalpine and alpine belts of the Albanian Alps (= Prokletije Mountain Range, Bjeshket e Nemuna) are presented. 92 lichenized and 26 lichenicolous fungi are new to Montenegro, 165 lichenized and 24 lichenicolous fungi are new to Kosovo, and 25 lichenized fungi (23 species) are new for the Balkan Peninsula. PMID- 26869729 TI - Numerical simulation of endocytosis: Viscous flow driven by membranes with non uniformly distributed curvature-inducing molecules. AB - The formation of membrane vesicles from a larger membrane that occurs during endocytosis and other cell processes are typically orchestrated by curvature inducing molecules attached to the membrane. Recent reports demonstrate that vesicles can form de novo in a few milliseconds. Membrane dynamics at these scales are strongly influenced by hydrodynamic interactions. To study this problem, we develop new diffuse interface models for the dynamics of inextensible vesicles in a viscous fluid with stiff, curvature-inducing molecules. The model couples the Navier-Stokes equations with membrane-induced bending forces that incorporate concentration-dependent bending stiffness coefficients and spontaneous curvatures, with equations for molecule transport and for a Lagrange multiplier to enforce local inextensibility. Two forms of surface transport equations are considered: Fickian surface diffusion and Cahn-Hilliard surface dynamics, with the former being more appropriate for small molecules and the latter being better for large molecules. The system is solved using adaptive finite element methods in 3D axisymmetric geometries. The results demonstrate that hydrodynamics can indeed enable the rapid formation of a small vesicle attached to the membrane by a narrow neck. When the Fickian model is used, this is a transient state with the steady state being a flat membrane with a uniformly distributed molecule concentration due to diffusion. When the Cahn-Hilliard model is used, molecule concentration gradients are sustained, the neck stabilizes and the system evolves to a steady-state with a small, compact vesicle attached to the membrane. By varying the membrane coverage of molecules in the Cahn-Hilliard model, we find that there is a critical (smallest) neck radius and a critical (fastest) budding time. These critical points are associated with changes in the vesicle morphology from spherical to mushroom-like as the molecule coverage on the membrane is increased. PMID- 26869728 TI - 3D Printing for Tissue Engineering. AB - Tissue engineering aims to fabricate functional tissue for applications in regenerative medicine and drug testing. More recently, 3D printing has shown great promise in tissue fabrication with a structural control from micro- to macro-scale by using a layer-by-layer approach. Whether through scaffold-based or scaffold-free approaches, the standard for 3D printed tissue engineering constructs is to provide a biomimetic structural environment that facilitates tissue formation and promotes host tissue integration (e.g., cellular infiltration, vascularization, and active remodeling). This review will cover several approaches that have advanced the field of 3D printing through novel fabrication methods of tissue engineering constructs. It will also discuss the applications of synthetic and natural materials for 3D printing facilitated tissue fabrication. PMID- 26869731 TI - An extensive analysis of the parity of broken 3-diamond partitions. AB - In 2007, Andrews and Paule introduced the family of functions [Formula: see text] which enumerate the number of broken k-diamond partitions for a fixed positive integer k. Since then, numerous mathematicians have considered partitions congruences satisfied by [Formula: see text] for small values of k. In this work, we provide an extensive analysis of the parity of the function [Formula: see text], including a number of Ramanujan-like congruences modulo 2. This will be accomplished by completely characterizing the values of [Formula: see text] modulo 2 for [Formula: see text] and any value of [Formula: see text]. In contrast, we conjecture that, for any integers [Formula: see text], [Formula: see text] and [Formula: see text] is infinitely often even and infinitely often odd. In this sense, we generalize Subbarao's Conjecture for this function [Formula: see text]. To the best of our knowledge, this is the first generalization of Subbarao's Conjecture in the literature. PMID- 26869730 TI - Response to Instruction in Preschool: Results of Two Randomized Studies with Children At Significant Risk of Reading Difficulties. AB - Although response-to-instruction (RTI) approaches have received increased attention, few studies have evaluated the potential impacts of RTI approaches with preschool populations. This manuscript presents results of two studies examining impacts of Tier II instruction with preschool children. Participating children were identified as substantially delayed in the acquisition of early literacy skills despite exposure to high-quality, evidence-based classroom instruction. Study 1 included 93 children (M age = 58.2 months; SD = 3.62) attending 12 Title I preschools. Study 2 included 184 children (M age = 58.2 months; SD = 3.38) attending 19 Title I preschools. The majority of children were Black/African American, and about 60% were male. In both studies, eligible children were randomized to receive either 11 weeks of need-aligned, small-group instruction or just Tier I. Tier II instruction in Study 1 included variations of activities for code- and language-focused domains with prior evidence of efficacy in non-RTI contexts. Tier II instruction in Study 2 included instructional activities narrower in scope, more intensive, and delivered to smaller groups of children. Impacts of Tier II instruction in Study 1 were minimal; however, there were significant and moderate-to-large impacts in Study 2. These results identify effective Tier II instruction but indicate that the context in which children are identified may alter the nature of Tier II instruction that is required. Children identified as eligible for Tier II in an RTI framework likely require more intensive and more narrowly focused instruction than do children at general risk of later academic difficulties. PMID- 26869732 TI - Sylow p-groups of polynomial permutations on the integers mod [Formula: see text]. AB - We enumerate and describe the Sylow p-groups of the groups of polynomial permutations of the integers mod [Formula: see text] for [Formula: see text] and of the pro-finite group which is the projective limit of these groups. PMID- 26869733 TI - Conjugation morphology of Zygogonium ericetorum (Zygnematophyceae, Charophyta) from a high alpine habitat. AB - Reproductive characteristics are important for defining taxonomic groups of filamentous Zygnematophyceae, but they have not been fully observed in the genus Zygogonium. Specimens of Z. ericetorum previously studied and used to clarify the generic concept lacked fertile material, which was obtained recently. This study illustrates for the first time, using color light microscopic and fluorescence images, a consequent conjugation stage in Z. ericetorum, including completely developed zygospores and purple cytoplasmic residue content left outside the zygospores, similar to aplanospore formation. Structures confirmed earlier reports and provided new observation informative regarding phylogenetically relevant reproductive characters of Z. ericetorum. PMID- 26869734 TI - What Counts as Scientific Data? A Relational Framework. AB - This paper proposes an account of scientific data that makes sense of recent debates on data-driven research, while also building on the history of data production and use particularly within biology. In this view, 'data' is a relational category applied to research outputs that are taken, at specific moments of inquiry, to provide evidence for knowledge claims of interest to the researchers involved. They do not have truth-value in and of themselves, nor can they be seen as straightforward representations of given phenomena. Rather, they are fungible objects defined by their portability and their prospective usefulness as evidence. PMID- 26869735 TI - You Cannot be Partially Pregnant: A Comparison of Divisible and Nondivisible Outcomes in Delay and Probability Discounting Studies. AB - Research by The Psychological Record, 64(3), 433-440. doi:10.1007/s40732-014-0052 9, (2014) demonstrated the novel finding that the magnitude effect for medical outcomes does not reverse across delay and probability discounting as it does for monetary outcomes. We suggest that a possible reason for the lack of a reverse magnitude effect in nonmonetary outcomes is incomparable divisibility of discounted alternatives. To test whether the lack of a reverse magnitude effect in probability discounting of medical outcomes is due to incomparable divisibility of treatment effects, 4 studies were conducted. In the replication study, the effect observed by The Psychological Record, 64(3), 433-440. doi:10.1007/s40732-014-0052-9, (2014) was marginally not significant, although it was directionally consistent with their prediction of steeper discounting of small medical outcomes (as compared to large, defined as brain cancer) both in time and probability discounting. Our manipulation by substituting a divisible outcome (body paralysis) for an indivisible one (brain cancer) did not, however, bring expected results. We discuss the explanations and possible implications of introduced division for divisible and nondivisible medical outcomes. PMID- 26869736 TI - Terricolous Lichens in the Glacier Forefield of the Gaisbergferner (Eastern Alps, Tyrol, Austria). AB - The investigation of lichens on soil, plant debris and terricolous mosses in the glacier forefield of the Gaisbergferner yielded 41 lichen taxa (39 species and 2 varieties) and one lichenicolous fungus. Three sampling sites were established at increasing distance from the glacier, in order to compare species diversity, abundance and composition. PMID- 26869737 TI - Terricolous Lichens in the Glacier Forefield of the Rotkees (Eastern Alps, South Tyrol, Italy). AB - The investigation of lichens on soil, plant debris and terricolous mosses in the glacier forefield of the Rotkees yielded 31 lichen taxa (29 species and 2 varieties) and one lichenicolous fungus. Micarea incrassata Hedl. (Lecanorales) is new to Italy. Three sampling sites were established at increasing distance from the glacier, in order to compare species diversity, abundance and composition. PMID- 26869738 TI - When glaciers and ice sheets melt: consequences for planktonic organisms. AB - The current melting of glaciers and ice sheets is a consequence of climatic change and their turbid meltwaters are filling and enlarging many new proglacial and ice-contact lakes around the world, as well as affecting coastal areas. Paradoxically, very little is known on the ecology of turbid glacier-fed aquatic ecosystems even though they are at the origin of the most common type of lakes on Earth. Here, I discuss the consequences of those meltwaters for planktonic organisms. A remarkable characteristic of aquatic ecosystems receiving the discharge of meltwaters is their high content of mineral suspensoids, so-called glacial flour that poses a real challenge for filter-feeding planktonic taxa such as Daphnia and phagotrophic groups such as heterotrophic nanoflagellates. The planktonic food-web structure in highly turbid meltwater lakes seems to be truncated and microbially dominated. Low underwater light levels leads to unfavorable conditions for primary producers, but at the same time, cause less stress by UV radiation. Meltwaters are also a source of inorganic and organic nutrients that could stimulate secondary prokaryotic production and in some cases (e.g. in distal proglacial lakes) also phytoplankton primary production. How changes in turbidity and in other related environmental factors influence diversity, community composition and adaptation have only recently begun to be studied. Knowledge of the consequences of glacier retreat for glacier-fed lakes and coasts will be crucial to predict ecosystem trajectories regarding changes in biodiversity, biogeochemical cycles and function. PMID- 26869739 TI - Intensified Religious Pluralism and De-differentiation: the British Example. AB - Drawing on surveys of religion and values in Great Britain, this paper suggests that Peter Berger's paradigm of two pluralisms can be usefully supplemented by taking account of a third kind of intensified pluralism. This involves the breakdown of the boundaries between religions, and between the religious and the secular, and is therefore a pluralism of de-differentiation. It helps explain many features of contemporary religion and identity, including the rise of the "nones" and the increasing reluctance of each new generation to identify with religious (and secular) labels and packages. PMID- 26869740 TI - Promoting Birth Parents' Relationships with their Toddlers upon Reunification: Results from Promoting First Relationships(r) Home Visiting Program. AB - Birth parents, once reunified with their child after a foster care placement, are in need of in-home support services to prevent reoccurrence of maltreatment and reentry into foster care, establish a strong relationship with their child, and enhance child well-being. Few studies have addressed the efficacy of home visiting services for reunified birth parents of toddlers. This study reports on the findings from a randomized control trial of a 10-week home visiting program, Promoting First Relationships(r) (Kelly, Sandoval, Zuckerman, & Buehlman, 2008), for a subsample of 43 reunified birth parents that were part of the larger trial. We describe how the elements of the intervention align with the needs of parents and children in child welfare. Although the sample size was small and most of the estimates of intervention effects were not statistically significant, the effect sizes and the pattern of results suggest that the intervention may have improved both observed parenting sensitivity and observed child behaviors as well as decreased parent report of child behavior problems. Implications are that providing in-home services soon after a reunification may be efficacious in strengthening birth parents' capacity to respond sensitively to their children as well as improving child social and emotional outcomes and well-being. PMID- 26869741 TI - Angiographic analysis for phantom simulations of endovascular aneurysm treatments with a new fully retrievable asymmetric flow diverter. AB - Digital Subtraction Angiography (DSA) is the main diagnostic tool for intracranial aneurysms (IA) flow-diverter (FD) assisted treatment. Based on qualitative contrast flow evaluation, interventionists decide on subsequent steps. We developed a novel fully Retrievable Asymmetric Flow-Diverter (RAFD) which allows controlled deployment, repositioning and detachment achieve optimal flow diversion. The device has a small low porosity or solid region which is placed such that it would achieve maximum aneurysmal in-jet flow deflection with minimum impairment to adjacent vessels. We tested the new RAFD using a flow-loop with an idealized and a patient specific IA phantom in carotid-relevant physiological conditions. We positioned the deflection region at three locations: distally, center and proximally to the aneurysm orifice and analyzed aneurysm dome flow using DSA derived maps for mean transit time (MTT) and bolus arrival times (BAT). Comparison between treated and untreated (control) maps quantified the RAFD positioning effect. Average MTT, related to contrast presence in the aneurysm dome increased, indicating flow decoupling between the aneurysm and parent artery. Maximum effect was observed in the center and proximal position (~75%) of aneurysm models depending on their geometry. BAT maps, correlated well with inflow jet direction and magnitude. Reduction and jet dispersion as high as about 50% was observed for various treatments. We demonstrated the use of DSA data to guide the placement of the RAFD and showed that optimum flow diversion within the aneurysm dome is feasible. This could lead to more effective and a safer IA treatment using FDs. PMID- 26869743 TI - Lichenized fungi of a chestnut grove in Livari (Rumija, Montenegro). AB - Sixty taxa (59 species and 1 variety) of lichenized fungi are reported from a chestnut grove in Livari. The majority of them (55 species and 1 variety) occurred on Castanea sativa. The recently described Xylographa soralifera is new to the Balkan Peninsula. The lichenicolous fungus Monodictys epilepraria growing on Lepraria rigidula is new to Montenegro. The lichen mycota is compared with similar localities in Italy and Switzerland. The species composition in Livari is most similar to the Montieri site in Tuscany. PMID- 26869742 TI - Micro-Computed tomography (CT) based assessment of dental regenerative therapy in the canine mandible model. AB - High-resolution 3D bone-tissue structure measurements may provide information critical to the understanding of the bone regeneration processes and to the bone strength assessment. Tissue engineering studies rely on such nondestructive measurements to monitor bone graft regeneration area. In this study, we measured bone yield, fractal dimension and trabecular thickness through micro-CT slices for different grafts and controls. Eight canines underwent surgery to remove a bone volume (defect) in the canine's jaw at a total of 44 different locations. We kept 11 defects empty for control and filled the remaining ones with three regenerative materials; NanoGen (NG), a FDA-approved material (n=11), a novel NanoCalcium Sulfate (NCS) material (n=11) and NCS alginate (NCS+alg) material (n=11). After a minimum of four and eight weeks, the canines were sacrificed and the jaw samples were extracted. We used a custom-built micro-CT system to acquire the data volume and developed software to measure the bone yield, fractal dimension and trabecular thickness. The software used a segmentation algorithm based on histograms derived from volumes of interest indicated by the operator. Using bone yield and fractal dimension as indices we are able to differentiate between the control and regenerative material (p<0.005). Regenerative material NCS showed an average 63.15% bone yield improvement over the control sample, NCS+alg showed 55.55% and NanoGen showed 37.5%. The bone regeneration process and quality of bone were dependent upon the position of defect and time period of healing. This study presents one of the first quantitative comparisons using non destructive Micro-CT analysis for bone regenerative material in a large animal with a critical defect model. Our results indicate that Micro-CT measurement could be used to monitor in-vivo bone regeneration studies for greater regenerative process understanding. PMID- 26869744 TI - Risananeiza crassaparies n. sp. from the upper Chattian of Porto Badisco (southern Apulia, Italy). AB - A new species of Rotaliidae, Risananeiza crassaparies n. sp., is described from the upper Chattian of the Porto Badisco Calcarenites (Salento Peninsula, Southern Italy). The studied specimens are assigned to the foraminiferal genus Risananeiza based on the presence of vertical canals in both the ventral and dorsal side of the test, and an intraseptal canal system that evolves into marginal sutural canals. The new species differs from the type species of the genus, R. pustulosa, in having a lower chamber lumen, and smaller dimension. PMID- 26869745 TI - Cultivation of shear stress sensitive and tolerant microalgal species in a tubular photobioreactor equipped with a centrifugal pump. AB - The tolerance to shear stress of Tetraselmis suecica, Isochrysis galbana, Skeletonema costatum, and Chaetoceros muelleri was determined in shear cylinders. The shear tolerance of the microalgae species strongly depends on the strain. I. galbana, S. costatum, and C. muelleri exposed to shear stress between 1.2 and 5.4 Pa resulted in severe cell damage. T. suecica is not sensitive to stresses up to 80 Pa. The possibility to grow these algae in a tubular photobioreactor (PBR) using a centrifugal pump for recirculation of the algae suspension was studied. The shear stresses imposed on the algae in the circulation tubes and at the pressure side of the pump were 0.57 and 1.82 Pa, respectively. The shear stress tolerant T. suecica was successfully cultivated in the PBR. Growth of I. galbana, S. costatum, and C. muelleri in the tubular PBR was not observed, not even at the lowest pumping speed. For the latter shear sensitive strains, the encountered shear stress levels were in the order of magnitude of the determined maximum shear tolerance of the algae. An equation was used to simulate the effect of possible damage of microalgae caused by passages through local high shear zones in centrifugal pumps on the total algae culture in the PBR. This simulation shows that a culture of shear stress sensitive species is bound to collapse after only limited number of passages, confirming the importance of considering shear stress as a process parameter in future design of closed PBRs for microalgal cultivation. PMID- 26869746 TI - Secure transport and adaptation of MC-EZBC video utilizing H.264-based transport protocols. AB - Universal Multimedia Access (UMA) calls for solutions where content is created once and subsequently adapted to given requirements. With regard to UMA and scalability, which is required often due to a wide variety of end clients, the best suited codecs are wavelet based (like the MC-EZBC) due to their inherent high number of scaling options. However, most transport technologies for delivering videos to end clients are targeted toward the H.264/AVC standard or, if scalability is required, the H.264/SVC. In this paper we will introduce a mapping of the MC-EZBC bitstream to existing H.264/SVC based streaming and scaling protocols. This enables the use of highly scalable wavelet based codecs on the one hand and the utilization of already existing network technologies without accruing high implementation costs on the other hand. Furthermore, we will evaluate different scaling options in order to choose the best option for given requirements. Additionally, we will evaluate different encryption options based on transport and bitstream encryption for use cases where digital rights management is required. PMID- 26869748 TI - Lichenized and lichenicolous fungi from the valley 'Ochsental' (Eastern Alps, Vorarlberg, Austria). AB - A list of 100 lichen species and 4 lichenicolous fungi from the valley 'Ochsental' is presented. Lecidea laboriosa is new to Austria. Lecanora swartzii, Orphniospora moriopsis, Protothelenella corrosa and the lichenicolous fungus Cercidospora stereocaulorum are new to the province of Vorarlberg. PMID- 26869747 TI - Neuromuscular development in Patellogastropoda (Mollusca: Gastropoda) and its importance for reconstructing ancestral gastropod bodyplan features. AB - Within Gastropoda, limpets (Patellogastropoda) are considered the most basal branching taxon and its representatives are thus crucial for research into evolutionary questions. Here, we describe the development of the neuromuscular system in Lottia cf. kogamogai. In trochophore larvae, first serotonin-like immunoreactivity (lir) appears in the apical organ and in the prototroch nerve ring. The arrangement and number of serotonin-lir cells in the apical organ (three flask-shaped, two round cells) are strikingly similar to those in putatively derived gastropods. First, FMRFamide-lir appears in veliger larvae in the Anlagen of the future adult nervous system including the cerebral and pedal ganglia. As in other gastropods, the larvae of this limpet show one main and one accessory retractor as well as a pedal retractor and a prototroch muscle ring. Of these, only the pedal retractor persists until after metamorphosis and is part of the adult shell musculature. We found a hitherto undescribed, paired muscle that inserts at the base of the foot and runs towards the base of the tentacles. An apical organ with flask-shaped cells, one main and one accessory retractor muscle is commonly found among gastropod larvae and thus might have been part of the last common ancestor. PMID- 26869749 TI - Merging Policy Initiatives and Developmental Perspectives in Early Intervention. AB - The provision of early intervention services for vulnerable children and their families is now both accepted and expected by the international community. This article considers the importance of a developmental perspective as an essential guide to early intervention service systems. Emphasized in this framework are three critical features: relationship formation, the continuity of interventions, and the comprehensiveness of interventions. Guidance to early intervention systems design with respect to structural and values principles is also discussed. Future advances in early intervention may well depend upon the merging of these perspectives to create policy initiatives to enhance early intervention systems. PMID- 26869750 TI - The suprachoroidal space: from potential space to a space with potential. AB - Recent advances have made it possible to image the suprachoroidal space, and the understanding of its clinical applications is currently being greatly expanded. This opinion piece covers the advances in imaging techniques that enable the demonstration of the suprachoroidal space, and its implication in various retinal pathologies. It also reviews its potential uses as a route for drug delivery for the treatment of retinal diseases, and its use in innovative surgical techniques. Current research is leading the way for the suprachoroidal space to be an aspect of retinal disease diagnosis, monitoring, medical treatment, and surgical manipulation. PMID- 26869752 TI - Erratum: Delayed manifestation of bilateral scleral thinning after I-BRITE((r)) procedure and review of literature for cosmetic eye-whitening procedures [Corrigendum]. AB - [This corrects the article on p. 445 in vol. 9, PMID: 25784790.]. PMID- 26869751 TI - Role of steroids in the treatment of bacterial keratitis. AB - Bacterial keratitis can lead to severe visual impairment from corneal ulceration, subsequent scarring, and possible perforation. The mainstay of treatment is topical antibiotics, whereas the use of adjunctive topical corticosteroid drops remains a matter of debate. Herein, we review the rationale for and against the use of topical corticosteroids and we assess their effectiveness and safety in the published randomized controlled trials that have evaluated their role as adjunctive therapy for bacterial corneal ulcers. In the largest study to date, the Steroids for Corneal Ulcers Trial, topical corticosteroid drops were neither helpful nor harmful for the 500 participants as a whole. However, subgroup analyses suggested that topical corticosteroids may be beneficial upon early administration (within 2-3 days after starting antibiotics) for more central corneal ulcers with poorer vision at presentation, for invasive Pseudomonas strains, and for non-Nocardia ulcers. These results are discussed within the limitations of the study. PMID- 26869754 TI - Comparison of surgical time and IOP spikes with two ophthalmic viscosurgical devices following Visian STAAR (ICL, V4c model) insertion in the immediate postoperative period. AB - PURPOSE: To compare the effect of two ocular viscosurgical devices (OVDs) on intraocular pressure (IOP) and surgical time in immediate postoperative period after bilateral implantable collamer lens (using the V4c model) implantation. METHODS: A total of 20 eligible patients were randomized to receive 2% hydroxypropylmethylcellulose (HPMC) in one eye and 1% hyaluronic acid in fellow eye. Time taken for complete removal of OVD and total surgical time were recorded. At the end of surgery, IOP was adjusted between 15 and 20 mmHg in both the eyes. RESULTS: Mean time for complete OVD evacuation and total surgical time were significantly higher in the HPMC group (P=0.00). Four eyes in the HPMC group had IOP spike, requiring treatment. IOP values with noncontact tonometry at 1, 2, 4, 24, and 48 hours were not statistically significant (P>0.05) for both the groups. CONCLUSION: The study concluded that 1% hyaluronic acid significantly reduces total surgical time, and incidence of acute spikes may be lower compared to 2% HPMC when used for implantable collamer lens (V4c model). PMID- 26869753 TI - Minimally invasive glaucoma surgery: current status and future prospects. AB - Minimally invasive glaucoma surgery aims to provide a medication-sparing, conjunctival-sparing, ab interno approach to intraocular pressure reduction for patients with mild-to-moderate glaucoma that is safer than traditional incisional glaucoma surgery. The current approaches include: increasing trabecular outflow (Trabectome, iStent, Hydrus stent, gonioscopy-assisted transluminal trabeculotomy, excimer laser trabeculotomy); suprachoroidal shunts (Cypass micro stent); reducing aqueous production (endocyclophotocoagulation); and subconjunctival filtration (XEN gel stent). The data on each surgical procedure for each of these approaches are reviewed in this article, patient selection pearls learned to date are discussed, and expectations for the future are examined. PMID- 26869756 TI - Electronic medical record and glaucoma medications: connecting the medication reconciliation with adherence. AB - PURPOSE: To evaluate consistency in documentation of glaucoma medications in the electronic medical record and identify which regimen patients adhere to when inconsistencies exist. Factors contributing to medication nonadherence are also explored. METHODS: Retrospective chart review of medication adherence encompassing 200 patients from three glaucoma physicians at a tertiary referral center over a 1-month period. Adherence was determined by the consistency between a patients stated medication regimen and either the active medication list in the electronic medical record, or the physicians planned medication regimen in the preceding clinic visit. Patient charts were also reviewed for patient sex, age, primary language, race, and total number of medications. RESULTS: A total of 160 charts showed consistency in documentation between the physician note and electronic medication reconciliation. Of those patients, 83.1% reported adherence with their glaucoma medication schedule. When there was a discrepancy in documentation (40 charts), 72.5% patients followed the physician-stated regimen vs 20% who followed neither vs 7.5% who followed the medical record (P<0.01). No difference in adherence was observed based on sex (P=0.912) or total number of medications taken (P=0.242). Language, both English- (P=0.075) and Haitian (P=0.10) -speaking populations, as well as race, Caucasian (P=0.31), African American (P=0.54), and Hispanic (P=0.58), had no impact on medication adherence. Patients over 80 years of age were more nonadherent as compared to other decades (P=0.04). CONCLUSION: Inconsistent documentation between the electronic medical record physician note and medication regimen may contribute to patient medication nonadherence. Patients over 80 years of age were associated with higher rates of nonadherence, while sex, total number of medications, race, and language had no interaction with medication adherence. PMID- 26869755 TI - Effect of coffee (caffeine) against human cataract blindness. AB - Previous biochemical and morphological studies with animal experiments have demonstrated that caffeine given topically or orally to certain experimental animal models has significant inhibitory effect on cataract formation. The present studies were undertaken to examine if there is a correlation between coffee drinking and incidence of cataract blindness in human beings. That has been found to be the case. Incidence of cataract blindness was found to be significantly lower in groups consuming higher amounts of coffee in comparison to the groups with lower coffee intake. Mechanistically, the caffeine effect could be multifactorial, involving its antioxidant as well as its bioenergetic effects on the lens. PMID- 26869757 TI - Sutureless intrascleral intraocular lens fixation with lamellar dissection of scleral tunnel. AB - PURPOSE: To report the results of sutureless scleral fixation of a posterior chamber intraocular lens (IOL) by using our developed simple technique. METHODS: We retrospectively reviewed the medical records of 48 eyes of 47 patients who underwent sutureless intrascleral IOL fixation by using our modified technique. A 25-gauge microvitreoretinal knife was used to perform sclerotomies and create limbus-parallel scleral tunnels with lamellar dissection in which the haptics were fixed. RESULTS: The IOLs were fixed and centered well. The mean follow-up period was 26.7 months. Postoperative complications included smooth vitreous hemorrhage in four eyes (8.3%), cystoid macular edema in two eyes (4.2%), and iris capture of the IOL in two eyes (4.2%). No other complications, such as breakage of the IOL, spontaneous IOL dislocation, or retinal detachment, were detected during the follow-up period. CONCLUSION: The lamellar dissection of the limbus-parallel scleral tunnel can simplify the forceps-assisted introduction of the haptics into the scleral tunnel, and this technique seemed to be safe. PMID- 26869758 TI - Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population. AB - PURPOSE: The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification. MATERIAL AND METHODS: A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain. RESULTS: The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2+/-32.9 vs 252.0+/-24.9 MUm; P=0.958) and in nepafenac group (250.8+/-34 vs 264.0+/-34.1 MUm; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0+/-24.9 vs 264.0+/-34.1 MUm; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. CONCLUSION: Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%. PMID- 26869759 TI - Vitrectomy in patients over 90 years of age. AB - PURPOSE: The aim of this study was to evaluate vitrectomy procedures performed in patients over 90 years of age at the Dokkyo Medical University Koshigaya Hospital (Koshigaya, Japan). PATIENTS AND METHODS: Vitrectomies were performed in nine eyes of nine patients who were over 90 years of age between May 2010 and March 2015. Factors such as the underlying vitreoretinal disease, preoperative and postoperative best-corrected visual acuity (BCVA), surgical time, postoperative body position, need for a second surgery, systemic disease, and intraoperative changes in systemic conditions have been evaluated. RESULTS: The most common cause of the underlying vitreoretinal disease was vitreous hemorrhage derived from age-related macular degeneration and posterior dislocation of the lens secondary to a posterior capsular rupture (two cases each). The mean values for the logarithm of the minimum angle of resolution BCVA were 2.15 preoperatively and 1.46 postoperatively (P=0.020, Wilcoxon signed-rank test). The mean surgical time was 109 minutes. Prone position was needed in two cases, and no second surgeries were needed. The most common cause of systemic disease was hypertension, which was found in six cases. Transient hypertension was found in two cases during surgery, and these patients were treated using intravenous calcium blocker injections. CONCLUSION: Patients over 90 years of age who underwent vitrectomy procedures did not have serious problems, except transient hypertension during surgery. The BCVA significantly improved. These results indicated that vitrectomies could be performed successfully in patients over 90 years of age. PMID- 26869760 TI - Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study. AB - PURPOSE: Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. METHOD: Thirty-eight (38) patients were randomly assigned to a 1-year, double blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. RESULTS: The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). CONCLUSION: The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. PMID- 26869761 TI - Antibiotic prophylaxis: different practice patterns within and outside the United States. AB - Endophthalmitis remains a rare but important cause of visual loss. Prophylaxis strategies are important to reduce rates of endophthalmitis after cataract surgery, intravitreal injection, and other procedures. There is substantial variability between the US and the rest of the world. During cataract surgery, intracameral antibiotics are commonly used in many nations, especially in Europe, but are less commonly used in the US. A randomized clinical trial from the European Society of Cataract and Refractive Surgeons reported an approximately fivefold reduction in endophthalmitis rates associated with intracameral cefuroxime but these results are controversial. There are no randomized clinical trials regarding endophthalmitis associated with intravitreal injection. Topical antibiotics are commonly used in many nations, but are less commonly used in the US. At this time, there is no global consensus and it appears unlikely that additional major clinical trials will conclusively define the optimal endophthalmitis prophylaxis techniques. PMID- 26869762 TI - Emerging treatments in Castleman disease - a critical appraisal of siltuximab. AB - Castleman disease (CD) is a rare, heterogeneous lymphoproliferative disorder for which no standard of care currently exists. Evidence that the pathophysiology of CD is fueled by excessive interleukin-6 (IL-6) has led to considerable interest in therapeutic targeting of this cytokine. Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD. PMID- 26869765 TI - Erratum: Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma [Corrigendum]. AB - [This corrects the article on p. 5785 in vol. 9.]. PMID- 26869764 TI - In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor--poly(lactic-co-glycolic-acid) microsphere. AB - OBJECTIVE: To study the degradation and basic fibroblast growth factor (bFGF) release activity of bFGF - poly(lactic-co-glycolic-acid) microsphere (bFGF-PLGA MS) under stress in vitro, including the static pressure and shearing force simulating mechanical environment of the joint cavity. METHOD: First, bFGF-PLGA MSs were created. Meanwhile, two self-made experimental instruments (static pressure and shearing force loading instruments) were initially explored to provide stress-simulating mechanical environment of the joint cavity. Then, bFGF PLGA MSs were loaded into the two instruments respectively, to study microsphere degradation and drug release experiments. In the static pressure loading experiment, normal atmospheric pressure loading (approximately 0.1 MPa), 0.35 MPa, and 4.0 MPa pressure loading and shaking flask oscillation groups were designed to study bFGF-PLGA MS degradation and bFGF release. In the shearing force loading experiment, a pulsating pump was used to give the experimental group an output of 1,000 mL/min and the control group an output of 10 mL/min to carry out bFGF-PLGA MS degradation and drug release experiments. Changes of bFGF PLGA MSs, including microsphere morphology, quality, weight-average molecular weight of polymer, and microsphere degradation and bFGF release, were analyzed respectively. RESULTS: In the static pressure loading experiment, bFGF-PLGA MSs at different pressure were stable initially. The trend of molecular weight change, quality loss, and bFGF release was consistent. Meanwhile, microsphere degradation and bFGF release rates in the 4.0 MPa pressure loading group were faster than those in the normal and 0.35 MPa pressure loading groups. It was the fastest in the shaking flask group, showing a statistically significant difference (P<0.0001). In the shearing force loading experiment, there were no distinctive differences in the rates of microsphere degradation and bFGF release between experimental and control group. Meanwhile, microsphere degradation and bFGF release rates by shaking flask oscillation were obviously faster than those by shearing force only (P<0.0001). CONCLUSION: There are significant effects on bFGF-PLGA MS degradation and bFGF release due to the interaction between extraction stress and time. Static pressure has a conspicuous influence on bFGF PLGA MS degradation and release, especially at a pressure of 4.0 MPa. The shearing force has a slight effect on bFGF-PLGA MS degradation and drug release. On the contrary, shaking flask oscillation has a significantly distinctive effect. PMID- 26869763 TI - Formulation, optimization, and pharmacodynamic evaluation of chitosan/phospholipid/beta-cyclodextrin microspheres. AB - Cholinergic neurotransmission loss is the main cause of cognitive impairment in patients with Alzheimer's disease. Phospholipids (PLs) play an essential role in memory and learning abilities. Moreover, PLs act as a source of choline in acetylcholine synthesis. This study aimed to prepare and optimize the formulation of chitosan/phospholipid/beta-cyclodextrin (CTS/PL/beta-CD) microspheres that can improve cognitive impairment. The CTS/PL/beta-CD microspheres were prepared by spray drying, and optimized with an orthogonal design. These microspheres were also characterized in terms of morphology, structure, thermostability, drug loading, and encapsulation efficiency. The spatial learning and memory of rats were evaluated using the Morris water maze test, and the neuroprotective effects of the CTS/PL/beta-CD micro-spheres were investigated by immunohistochemistry. Scanning electron microscopic images showed that the CTS/PL/beta-CD microspheres were spherical with slightly wrinkled surfaces. Fourier transform infrared spectroscopy and differential scanning calorimetry proved that PLs formed hydrogen bonds with the amide group of CTS and the hydroxyl group of beta-CD. The learning and memory abilities of rats in the treated group significantly improved compared with those in the model group. Immunohistochemical analysis revealed that treatment with the CTS/PL/beta-CD microspheres attenuated the expression of protein kinase C-delta and inhibited the activation of microglias. These results suggest that the optimized microspheres have the potential to be used in the treatment of Alzheimer's disease. PMID- 26869766 TI - Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+) subset proliferation. AB - Magnesium isoglycyrrhizinate (MGL) is a new stereoisomer of glycyrrhizic acid, which is clinically used as a hepatoprotective medicine with more potent effects and less side effects than glycyrrhizic acid. This study was designed to evaluate the protective effects and possible mechanism of MGL against concanavalin A (Con A)-induced autoimmune hepatitis. Hepatitis was induced by Con A in C57/6J mice with or without MGL administration; injury score and serum ALT were evaluated. The CD4(+) T-cells were isolated from splenocytes and challenged with Con A after coculturing with MGL. The injury score was significantly improved in MGL-treated mice after Con A challenging for 12 and 24 hours compared with those merely challenged with Con A. Similar trends were observed in the serum levels of ALT and AST. The most interesting result was that MGL administration significantly decreased the frequency of CD4(+)CD25(-)CD69(+) T-cells rather than CD4(+)CD25(+)CD69(+) T-cells in peripheral blood mononuclear cells, after Con A challenging 12 and 24 hours. Moreover, the serum ALT levels were markedly correlated with the frequency of CD4(+)CD25(-)CD69(+) cells, but only weakly correlated with CD4(+)CD25(+)CD69(+) cells in peripheral blood mononuclear cells. More importantly, MGL (5 mg/mL) almost completely eliminated the proliferation of the CD25(-)CD69(+) subset in primary CD4(+) T-cells after Con A challenge. Compared with merely Con A-challenged mice, those with MGL administration significantly demonstrated decreased NALP3, NLRP6, and caspase-3 expression, in which the NALP3 and caspase-3 downregulated in a dose-dependent manner. Our results indicate that MGL may have potential as a therapeutic agent in autoimmune hepatitis by ameliorating liver injury. Its molecular mechanism may be involved in inhibiting CD4(+)CD25(-)CD69(+) subset proliferation and downregulating inflammasome expression in liver tissue. PMID- 26869767 TI - Determination of the binding mode for anti-inflammatory natural product xanthohumol with myeloid differentiation protein 2. AB - It is recognized that myeloid differentiation protein 2 (MD-2), a coreceptor of toll-like receptor 4 (TLR4) for innate immunity, plays an essential role in activation of the lipopolysaccharide signaling pathway. MD-2 is known as a neoteric and suitable therapeutical target. Therefore, there is great interest in the development of a potent MD-2 inhibitor for anti-inflammatory therapeutics. Several studies have reported that xanthohumol (XN), an anti-inflammatory natural product from hops and beer, can block the TLR4 signaling by binding to MD-2 directly. However, the interaction between MD-2 and XN remains unknown. Herein, our work aims at characterizing interactions between MD-2 and XN. Using a combination of experimental and theoretical modeling analysis, we found that XN can embed into the hydrophobic pocket of MD-2 and form two stable hydrogen bonds with residues ARG-90 and TYR-102 of MD-2. Moreover, we confirmed that ARG-90 and TYR-102 were two necessary residues during the recognition process of XN binding to MD-2. Results from this study identified the atomic interactions between the MD-2 and XN, which will contribute to future structural design of novel MD-2 targeting molecules for the treatment of inflammatory diseases. PMID- 26869769 TI - Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials. AB - OBJECTIVE: Eldecalcitol (ELD) is an active form of vitamin D analog that has been approved for the treatment of osteoporosis in Japan. Over recent years, a number of multicenter, randomized controlled clinical trials have been conducted. Our goal is to comprehensively summarize the results from these studies. METHODS: We searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 28, 2015. Each database was searched using search terms "Eldecalcitol" and "ED-71" and the results were combined. The retrieved data from three independent clinical trials included a total of 1,332 patients with osteoporosis. After the data were pooled from three trials, RevMan software was used to conduct meta-analyses to determine the effects of ELD on bone mineral density (BMD) and bone turnover marker (BTM) type I collagen amino terminal telopeptide (NTX). Effects of ELD on some of the bone formation and bone resorption parameters, incidence of vertebral fractures at the lower spine, and health-related quality of life (HRQOL) in patients with osteoporosis were also summarized. RESULTS: With a test for overall effect Z=6.35, ELD could increase lumbar BMD (P<0.00001). In comparison with alphacalcidol, ELD suppressed the NTX level to a greater degree (test for overall effect Z=3.82,P<0.0001). ELD was also found to suppress bone alkaline phosphatase (BALP) by 19% (P<0.01) and osteocalcin by 19% (P<0.01) at the dose of 0.75 MUg/day. Compared to alfacalcidol, ELD showed higher potency in suppressing serum BALP (26+/-9 vs 32+/ 11 U/L,P<0.05) and amino-terminal propeptide of procollagen I (PINP) (42+/-15 vs 59+/-23 ng/mL,P<0.05). In addition, ELD was found to be more effective in reducing the incidence of vertebral fractures at the lower spine (P=0.029). CONCLUSION: Our meta-analysis showed that ELD was more potent than alphacalcidol in reducing BTM (NTX). Clinical data together suggest that ELD is efficient in treating osteoporosis by increasing lumbar BMD; suppressing BTMs, including NTX, BALP, osteocalcin, and PINP; resulting in the reduction in the incidence of vertebral fractures at the lower spine; and increasing the HRQOL in patients with osteoporosis. PMID- 26869770 TI - Barriers to uptake of prevention of mother-to-child transmission of HIV services among mothers of vertically infected HIV-seropositive infants in Makurdi, Nigeria. AB - BACKGROUND: Perinatal transmission of human immunodeficiency virus (HIV) continues in Nigeria because of the poor use of prevention of mother-to-child transmission of HIV (PMTCT) services. This study reports on the barriers preventing mothers of vertically infected HIV-seropositive infants to use the PMTCT services at the Federal Medical Centre, Makurdi, Nigeria. METHODS: This is a descriptive study conducted between January and April, 2014. A quantitative survey was applied to detect barriers along the PMTCT services cascade among 52 mothers of vertically infected HIV-seropositive infants. This includes 22 women who attended antenatal care at the Federal Medical Centre (designated as Group A mothers) and 30 women who did not receive any form of PMTCT service (Group B mothers). The study was supplemented with a focused group discussion involving 12 discussants from the two groups. RESULTS: In the quantitative assessment: among the Group A mothers, falling asleep was the most common reason (n=22, 100%) for missing therapeutic/prophylactic antiretroviral medicine; financial constraint (n=22, 100%) was the most common reason for antenatal care visit defaults; and a lot of the mothers (n=11, 50.0%) did not give nevirapine to their newborns because they delivered at home. Among Group B mothers, unawareness of HIV seropositive status was the most common reason (n=28, 93.3%) given for not accessing PMTCT services. In the qualitative study: noninvolvement of male partners, stigma and discrimination experienced by HIV-seropositive mothers, financial constraints in couples, involvement of traditional birth attendants in antenatal care and delivery of HIV-infected women, unawareness of HIV seropositive status by pregnant women, poor health system, and the lack of funding for PMTCT services at private and rural health facilities were the major barriers preventing the use of PMTCT services. CONCLUSION: In order to reduce the missed opportunities for PMTCT interventions in Makurdi and by extension the Benue State it represents in Nigeria, strong political and financial commitments are needed to overcome the identified barriers. PMID- 26869768 TI - Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. AB - Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID- 26869771 TI - Reducing the risk of venous thromboembolism using apixaban - patient perspectives and considerations. Should more attention be given to females? AB - BACKGROUND: New oral anticoagulant agents, such as apixaban, rivaroxaban, dabigatran, or endoxaban, have recently become for patients an alternative option to conventional treatment in the therapy of venous thromboembolism (VTE). Thus, we aimed to review the available information on adverse events (AEs) of apixaban compared to conventional therapy (heparin or vitamin K antagonists) in randomized controlled trials (RCTs) on patients treated for VTE, with a particular attention to sex subgroups. METHODS: An electronic search in MEDLINE and Embase was performed by using the keywords "apixaban" and "venous thromboembolism". All RCTs focused on apixaban in the treatment and prevention of VTE were evaluated for the presence of AEs. AEs were classified as serious, bleeding, and cause of discontinuation. Moreover, we also searched by using the keywords "gender" and "venous thromboembolism" and "anticoagulants". RESULTS: Considering all subjects enrolled in the eleven RCTs as a whole to investigate the occurrence of AEs, we extrapolated an events/subjects rate of 57.8% for AEs (6,445/11,144), 7.7% for serious AEs (975/12,647), 9.1% for bleeding events (1,229/13,454), and 3.2% for discontinuation of apixaban (421/13,039). The percentage of AEs was lower in subjects treated with apixaban than in those treated with conventional VTE therapy (53% vs 56.3%, respectively). However, only one study provided data on separate analysis by sex of either efficacy or safety of apixaban. CONCLUSION: Under the patient's perspective, apixaban could represent a good choice in the treatment of VTE, due to its pharmacological, economical, and safety profile. These positive aspects are certainly present in both sexes, since the available studies include a correct percentage of women, but data with separate analyses by sex are extremely limited. Future clinical trials should include in their results on clinical impact and outcomes a stratification by sex, and studies aimed to evaluate possible sex-related differences for these drugs should be strongly encouraged. PMID- 26869772 TI - Patterns of analgesic adherence predict health care utilization among outpatients with cancer pain. AB - BACKGROUND: Studies in chronic noncancer pain settings have found that opioid use increases health care utilization. Despite the key role of analgesics, specifically opioids, in the setting of cancer pain, there is no literature to our knowledge about the relationship between adherence to prescribed around-the clock (ATC) analgesics and acute health care utilization (hospitalization) among patients with cancer pain. PURPOSE: To identify adherence patterns over time for cancer patients taking ATC analgesics for pain, cluster these patterns into adherence types, combine the types into an adherence risk factor for hospitalization, identify other risk factors for hospitalization, and identify risk factors for inconsistent analgesic adherence. MATERIALS AND METHODS: Data from a 3-month prospective observational study of patients diagnosed with solid tumors or multiple myeloma, having cancer-related pain, and having at least one prescription of oral ATC analgesics were collected. Adherence data were collected electronically using the medication event-monitoring system. Analyses were conducted using adaptive modeling methods based on heuristic search through alternative models controlled by likelihood cross-validation scores. RESULTS: Six adherence types were identified and combined into the risk factor for hospitalization of inconsistent versus consistent adherence over time. Twenty other individually significant risk factors for hospitalization were identified, but inconsistent analgesic adherence was the strongest of these predictors (ie, generating the largest likelihood cross-validation score). These risk factors were adaptively combined into a model for hospitalization based on six pairwise interaction risk factors with exceptional discrimination (ie, area under the receiver-operating-characteristic curve of 0.91). Patients had from zero to five of these risk factors, with an odds ratio of 5.44 (95% confidence interval 3.09 9.58) for hospitalization, with a unit increase in the number of such risk factors. CONCLUSION: Inconsistent adherence to prescribed ATC analgesics, specifically the interaction of strong opioids and inconsistent adherence, is a strong risk factor for hospitalization among cancer outpatients with pain. PMID- 26869773 TI - What influences patients' acceptance of a blood pressure telemonitoring service in primary care? A qualitative study. AB - BACKGROUND: Telemonitoring of home blood pressure (BP) is found to have a positive effect on BP control. Delivering a BP telemonitoring service in primary care offers primary care physicians an innovative approach toward management of their patients with hypertension. However, little is known about patients' acceptance of such service in routine clinical care. OBJECTIVE: This study aimed to explore patients' acceptance of a BP telemonitoring service delivered in primary care based on the technology acceptance model (TAM). METHODS: A qualitative study design was used. Primary care patients with uncontrolled office BP who fulfilled the inclusion criteria were enrolled into a BP telemonitoring service offered between the period August 2012 and September 2012. This service was delivered at an urban primary care clinic in Kuala Lumpur, Malaysia. Twenty patients used the BP telemonitoring service. Of these, 17 patients consented to share their views and experiences through five in-depth interviews and two focus group discussions. An interview guide was developed based on the TAM. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was used for analysis. RESULTS: Patients found the BP telemonitoring service easy to use but struggled with the perceived usefulness of doing so. They expressed confusion in making sense of the monitored home BP readings. They often thought about the implications of these readings to their hypertension management and overall health. Patients wanted more feedback from their doctors and suggested improvement to the BP telemonitoring functionalities to improve interactions. Patients cited being involved in research as the main reason for their intention to use the service. They felt that patients with limited experience with the internet and information technology, who worked out of town, or who had an outdoor hobby would not be able to benefit from such a service. CONCLUSION: Patients found BP telemonitoring service in primary care easy to use but needed help to interpret the meanings of monitored BP readings. Implementations of BP telemonitoring service must tackle these issues to maximize the patients' acceptance of a BP telemonitoring service. PMID- 26869774 TI - Japanese physicians' preferences for decision making in rheumatoid arthritis treatment. AB - BACKGROUND: Rheumatoid arthritis (RA) is a complex chronic illness requiring continued medical care. During the past decade, the therapeutic options for RA have increased significantly; these often have a higher risk of adverse effects and are more expensive than traditional drugs. Rheumatologists may hence face difficulties when deciding on the optimal modality in initiating or changing treatment. The aim of this study was to explore the Japanese physicians' usual style of and preferences for decision making regarding RA treatment. METHODS: This was a cross-sectional study conducted using an Internet survey. Respondents were asked about their usual style of making treatment decisions (perceived style), and their perception of the importance of physicians' actions and patients' attitudes. RESULTS: Of the 485 physicians who were sent the questionnaire, 157 responded completely (response rate: 32.3%). Ninety-two percent of the respondents were men, and 57% were clinicians with more than 20 years of experience. Their specialties were general medicine (29%), rheumatology (27%), orthopedics (31%), and rehabilitation (12%). Sixty-one (39%) stated that they usually presented multiple treatment options to their patients and selected a decision for them, 42 (27%) shared the decision making with their patients, 34 (22%) let their patients choose the treatment, and 20 (13%) made the treatment decision for the patients. Physicians using the shared decision making (SDM) style desired for their patients to have supportive family and friends, to discuss with nurses, and to follow the doctors' directions more strongly compared with physicians using the other styles. There were no significant differences in sex, duration of clinical experience, major place of clinical work, and number of patients per month by the styles. More number of rheumatologists and physicians with specialist qualifications stated that they practiced SDM. CONCLUSION: To enhance patient participation, physicians need to recognize the importance of discussing treatment options with patients in addition to giving them information. PMID- 26869775 TI - Ratio between carotid artery stiffness and blood flow - a new ultrasound index of ischemic leukoaraiosis. AB - BACKGROUND: Ischemic leukoaraiosis (ILA) is associated with cognitive decline and aging. Its pathophysiology is believed to be ischemic in origin due to its association with cerebrovascular risk factors and similarity in location to lacunar infarctions. ILA diagnosis is still based on magnetic resonance imaging (MRI) as well as exclusion of other causes of white matter hyperintensities. So far, there are no known confirming diagnostic tests of ILA. Ultrasound studies have recently shown increased large artery stiffness, increased cerebrovascular resistance, and lower cerebral blood flow in patients with ILA. Increased arterial stiffness and decreased blood flow could have a synergistic effect, and their ratio could be a useful diagnostic index of ILA. METHODS: In this post hoc analysis, we introduced new ILA indices (ILAi) that are ratios of the carotid stiffness parameters (pulse wave velocity beta [PWVbeta], pressure-strain elasticity modulus [Ep], beta index), and diastolic and mean blood flows in the internal carotid artery: Q-ICAd and Q-ICAm. We compared the ILAi of 52 patients with ILA and 44 sex- and risk factor-matched controls with normal MRI of the head. ILA diagnosis was based on MRI and exclusion of other causes of white matter hyperintensities. The diagnostic significance of ILAi for the prediction of ILA was analyzed. RESULTS: All ILAi significantly differed between the groups; the most significant were PWVbeta/Q-ICAd (ILA group: 1.96+/-0.64 vs control group: 1.56+/-0.40, P=0.001) and PWVbeta/Q-ICAm (ILA group: 1.13+/-0.32 vs control group: 0.94+/-0.25, P=0.003). All ILAi were significantly associated with ILA (P<0.01) and were significant independent predictors of ILA. All ILAi were also sensitive and specific for predicting ILA (area under the curve: 0.632 0.683, P<0.05). CONCLUSION: The new ultrasound indices significantly differed between patients with ILA and the control group and were significant predictors of ILA. A combination of lower carotid blood flow and increased carotid stiffness represented as ILAi probably has a diagnostic value in patients with ILA. PMID- 26869776 TI - Physicians' use of computerized clinical decision supports to improve medication management in the elderly - the Seniors Medication Alert and Review Technology intervention. AB - BACKGROUND: Elderly people (aged 65 years or more) are at increased risk of polypharmacy (five or more medications), inappropriate medication use, and associated increased health care costs. The use of clinical decision support (CDS) within an electronic medical record (EMR) could improve medication safety. METHODS: Participatory action research methods were applied to preproduction design and development and postproduction optimization of an EMR-embedded CDS implementation of the Beers' Criteria for medication management and the Cockcroft Gault formula for estimating glomerular filtration rates (GFR). The "Seniors Medication Alert and Review Technologies" (SMART) intervention was used in primary care and geriatrics specialty clinics. Passive (chart messages) and active (order-entry alerts) prompts exposed potentially inappropriate medications, decreased GFR, and the possible need for medication adjustments. Physician reactions were assessed using surveys, EMR simulations, focus groups, and semi-structured interviews. EMR audit data were used to identify eligible patient encounters, the frequency of CDS events, how alerts were managed, and when evidence links were followed. RESULTS: Analysis of subjective data revealed that most clinicians agreed that CDS appeared at appropriate times during patient care. Although managing alerts incurred a modest time burden, most also agreed that workflow was not disrupted. Prevalent concerns related to clinician accountability and potential liability. Approximately 36% of eligible encounters triggered at least one SMART alert, with GFR alert, and most frequent medication warnings were with hypnotics and anticholinergics. Approximately 25% of alerts were overridden and ~15% elicited an evidence check. CONCLUSION: While most SMART alerts validated clinician choices, they were received as valuable reminders for evidence-informed care and education. Data from this study may aid other attempts to implement Beers' Criteria in ambulatory care EMRs. PMID- 26869777 TI - Potential contribution of diabetes mellitus to orthostatic blood pressure fall and conversion of mild cognitive impairment to dementia. PMID- 26869778 TI - Can we do better? Economic analysis of human resource investment to improve home care service for the elderly in Serbia. AB - BACKGROUND: Social services aimed at the elderly are facing great challenges caused by progressive aging of the global population but also by the constant pressure to spend funds in a rational manner. PURPOSE: This paper focuses on analyzing the investments into human resources aimed at enhancing home care for the elderly since many countries have recorded progress in the area over the past years. The goal of this paper is to stress the significance of performing an economic analysis of the investment. METHODS: This paper combines statistical analysis methods such as correlation and regression analysis, methods of economic analysis, and scenario method. RESULTS: The economic analysis of investing in human resources for home care service in Serbia showed that the both scenarios of investing in either additional home care hours or more beneficiaries are cost efficient. However, the optimal solution with the positive (and the highest) value of economic net present value criterion is to invest in human resources to boost the number of home care hours from 6 to 8 hours per week and increase the number of the beneficiaries to 33%. CONCLUSION: This paper shows how the statistical and economic analysis results can be used to evaluate different scenarios and enable quality decision-making based on exact data in order to improve health and quality of life of the elderly and spend funds in a rational manner. PMID- 26869780 TI - A possible pathological link among swallowing dysfunction, gastro-esophageal reflex, and sleep apnea in acute exacerbation in COPD patients. PMID- 26869779 TI - An exploratory intervention study suggests clinical benefits of training in chronic stroke to be paralleled by changes in brain activity using repeated fMRI. AB - PURPOSE: Previous studies demonstrated changes in sensorimotor network activation over time after stroke that have been interpreted as partly compensatory. Locomotor and balance trainings may improve both mobility and cognition even in chronic stroke and thereby impact on cerebral activation patterns. We here aimed at testing these assumptions in an exploratory study to inform subsequent larger intervention studies. PATIENTS AND METHODS: Eight patients (73.3+/-4.4 years) with a chronic lacunar stroke (mean interval 3.7 years after the acute event with a range from 2 to 4 years) and residual leg paresis leading to gait disturbance received a guided 5-week training focusing on mobility, endurance, and coordination. Before and afterward, they underwent clinical, neuropsychological, and gait assessments and brain MRI at 3 T including a functional ankle movement paradigm. Sixteen healthy controls (HCs; 68.8+/-5.4 years) followed the same protocol without intervention. RESULTS: After training, patients had improved in mobility, memory, and delayed recall of memory. While cerebral activations in HC remained completely unaltered, patients showed increased activations in the right precentral gyrus, the right and left superior frontal gyri, and the right frontal lobe, with bipedal ankle movements after training. CONCLUSION: In this exploratory study of chronic stroke, we found not only significant effects of physical training on mobility but also distinct aspects of cognition already with a small number of highly selected patients. These improvements were paralleled by alterations in cerebral activity possibly reflecting neuronal plasticity. Larger studies including randomization are needed. PMID- 26869781 TI - Sex differences in reported and objectively measured sleep in COPD. AB - BACKGROUND: The aim was to assess and compare reported sleep disturbances and objectively measured sleep in men and women with COPD compared with controls and also explore sex differences. METHODS: A total of 96 patients with COPD and 90 age- and sex-matched controls answered a sleep questionnaire, underwent ambulatory polysomnography, a post-bronchodilatory spirometry, and blood sampling. RESULTS: Of the patients with COPD, 51% reported sleep disturbances as compared with 31% in controls (P=0.008). Sleep disturbances were significantly more prevalent in males with COPD compared with controls, whereas there was no significant difference in females. The use of hypnotics was more common among patients with COPD compared with controls, both in men (15% vs 0%, P=0.009) and women (36% vs 16%, P=0.03). The men with COPD had significantly longer recorded sleep latency than the male control group (23 vs 9.3 minutes, P<0.001), while no corresponding difference was found in women. In men with COPD, those with reported sleep disturbances had lower forced vital capacity, higher C-reactive protein, myeloperoxidase, and higher prevalence of chronic bronchitis. CONCLUSION: The COPD was associated with impaired sleep in men while the association was less clear in women. This was also confirmed by recorded longer sleep latency in male subjects with COPD compared with controls. PMID- 26869782 TI - Effect of salmeterol/fluticasone combination on the dynamic changes of lung mechanics in mechanically ventilated COPD patients: a prospective pilot study. AB - BACKGROUND: The combined therapy of inhaled corticosteroids and long-acting beta 2 agonists for mechanically ventilated patients with COPD has never been explored. Therefore, the aim of this study was to investigate their dynamic effects on lung mechanics and gas exchange. MATERIALS AND METHODS: Ten mechanically ventilated patients with resolution of the causes of acute exacerbations of COPD were included. Four puffs of salmeterol 25 MUg/fluticasone 125 MUg combination therapy were administered. Lung mechanics, including maximum resistance of the respiratory system (Rrs), end-inspiratory static compliance, peak inspiratory pressure (PIP), plateau pressure, and mean airway pressure along with gas exchange function were measured and analyzed. RESULTS: Salmeterol/fluticasone produced a significant improvement in Rrs and PIP after 30 minutes. With regard to changes in baseline values, salmeterol/fluticasone inhalation had a greater effect on PIP than Rrs. However, the therapeutic effects seemed to lose significance after 3 hours of inhaled corticosteroid/long-acting beta-2 agonist administration. CONCLUSION: The combination of salmeterol/fluticasone-inhaled therapy in mechanically ventilated patients with COPD had a significant benefit in reducing Rrs and PIP. PMID- 26869783 TI - The changing nature of chronic care and coproduction of care between primary care professionals and patients with COPD and their informal caregivers. AB - The aim of this study was to investigate whether care delivery in accordance with a care model is associated with co-productive relationships between professionals and COPD patients and their informal caregivers. A co-productive relationship refers to productive patient-professional interaction or shared decision making. This cross-sectional study was conducted in 2014 among 411 patients (out of 981) enrolled in the Dutch COPD care program Kennemer Lucht and 62 professionals treating them (out of 97). Kennemer Lucht COPD involved multicomponent interventions within all six dimensions of the chronic care model (organizational support, community, self-management, decision support, delivery system design, and information and communications technology) to improve the quality of care for patients with COPD. This approach was expected to improve relational coproduction of care between professionals and patients with COPD and their informal caregivers. Results show clearly that the perceived quality of chronic care delivery is related significantly to productive interaction/relational coproduction of care. The strength of the relationship between perceptions of quality of chronic care and relational coproduction among patients is strong (r=0.5; P<=0.001) and among professionals moderate (r=0.4; P<=0.001 relational coproduction with patients and informal caregivers). Furthermore, patients' perceptions of the quality of chronic care were associated with the existence of productive interaction with health care professionals (beta=0.7; P<=0.001). The changing nature of chronic care is associated with coproduction of care, leading to the development of more productive relationships between primary care professionals and COPD patients and their informal caregivers. Further research is necessary to determine how best to sustain these developments. PMID- 26869785 TI - A novel type of self-assembled nanoparticles as targeted gene carriers: an application for plasmid DNA and antimicroRNA oligonucleotide delivery. AB - In this study, a new type of amphiphilic cetylated polyethyleneimine (PEI) was synthesized, and then polylactic-co-glycolic acid (PLGA)/cetylated PEI/hyaluronic acid nanoparticles (PCPH NPs) were developed by self-assembly as a novel type of gene-delivering vehicle. The PCPH NPs showed good DNA-condensation ability by forming polyplexes with small particle size and positive zeta potential. The transfection efficiency and cytotoxicity of PCPH NPs were evaluated as plasmid DNA vectors to transfect HepG2 in vitro. PCPH NPs exhibited much lower cytotoxicity and higher gene-transfection efficiency than PEI (25,000) and commercial transfection reagents. Furthermore, PCPH NPs were used as an anti-miR 221 vector for transfecting HepG2 cells, and anti-miR-221 was effectively transfected into cells and produced a greater inhibitory effect on cancer-cell growth by PCPH NPs. These results demonstrate that PCPH NPs can be a promising nonviral vector for gene-delivery systems. PMID- 26869784 TI - Differences in the effects of Asian dust on pulmonary function between adult patients with asthma and those with asthma-chronic obstructive pulmonary disease overlap syndrome. AB - BACKGROUND: Asian dust (AD) exposure exacerbates pulmonary dysfunction in patients with asthma. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS), characterized by coexisting symptoms of asthma and chronic obstructive pulmonary disease, is considered a separate disease entity. Previously, we investigated the effects of AD on pulmonary function in adult patients with asthma. Here, we present the findings of our further research on the differences in the effects of AD exposure on pulmonary function between patients with asthma alone and those with ACOS. METHODS: Between March and May 2012, we conducted a panel study wherein we monitored daily peak expiratory flow (PEF) values in 231 adult patients with asthma. These patients were divided into 190 patients with asthma alone and 41 patients with ACOS in this study. Daily AD particle levels were measured using light detection and ranging systems. Two heavy AD days (April 23 and 24) were determined according to the Japan Meteorological Agency definition. A linear mixed model was used to estimate the association between PEF and AD exposure. RESULTS: Increments in the interquartile range of AD particles (0.018 km(-1)) led to PEF changes of -0.50 L/min (95% confidence interval, -0.98 to -0.02) in patients with asthma alone and -0.11 L/min (-0.11 to 0.85) in patients with ACOS. The PEF changes after exposure to heavy AD were -2.21 L/min (-4.28 to -0.15) in patients with asthma alone and 2.76 L/min (-6.86 to 1.35) in patients with ACOS. In patients with asthma alone, the highest decrease in PEF values was observed on the heavy AD day, with a subsequent gradual increase over time. CONCLUSION: Our results suggest that the effects of AD exposure on pulmonary function differ between patients with asthma alone and ACOS, with the former exhibiting a greater likelihood of decreased pulmonary function after AD exposure. PMID- 26869786 TI - Enhanced osteogenic activity and anti-inflammatory properties of Lenti-BMP-2 loaded TiO2 nanotube layers fabricated by lyophilization following trehalose addition. AB - To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1beta and tumor necrosis factor-alpha production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs. PMID- 26869787 TI - Miconazole-loaded solid lipid nanoparticles: formulation and evaluation of a novel formula with high bioavailability and antifungal activity. AB - BACKGROUND AND OBJECTIVE: Miconazole is a broad-spectrum antifungal drug that has poor aqueous solubility (<1 ug/mL); as a result, a reduction in its therapeutic efficacy has been reported. The aim of this study was to formulate and evaluate miconazole-loaded solid lipid nanoparticles (MN-SLNs) for oral administration to find an innovative way to alleviate the disadvantages associated with commercially available capsules. METHODS: MN-SLNs were prepared by hot homogenization/ultrasonication. The solubility of miconazole in different solid lipids was measured. The effect of process variables, such as surfactant types, homogenization and ultrasonication times, and the charge-inducing agent on the particle size, zeta potential, and encapsulation efficiency were determined. Furthermore, in vitro drug release, antifungal activity against Candida albicans, and in vivo pharmacokinetics were studied in rabbits. RESULTS: The MN-SLN, consisting of 1.5% miconazole, 2% Precirol ATO5, 2.5% Cremophor RH40, 0.5% Lecinol, and 0.1% Dicetylphosphate, had an average diameter of 23 nm with a 90.2% entrapment efficiency. Furthermore, the formulation of MN-SLNs enhanced the antifungal activity compared with miconazole capsules. An in vivo pharmacokinetic study revealed that the bioavailability was enhanced by >2.5-fold. CONCLUSION: MN SLN was more efficient in the treatment of candidiasis with enhanced oral bioavailability and could be a promising carrier for the oral delivery of miconazole. PMID- 26869788 TI - Liver-targeting Resibufogenin-loaded poly(lactic-co-glycolic acid)-D-alpha tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy. AB - Liver cancer remains a major problem around the world. Resibufogenin (RBG) is a major bioactive compound that was isolated from Chansu (also called toad venom or toad poison), which is a popular traditional Chinese medicine that is obtained from the skin secretions of giant toads. RBG has strong antitumor effects, but its poor aqueous solubility and its cardiotoxicity have limited its clinical use. The aim of this study was to formulate RBG-loaded poly(lactic-co-glycolic acid) (PLGA)-D-alpha-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RPTN) to enhance the treatment of liver cancer. RPTN, RBG-loaded PLGA nanoparticle (RPN), and RBG/coumarin-6-loaded PLGA-D-alpha-tocopheryl polyethylene glycol 1000 succinate nanoparticle (RCPTN) were prepared. The cellular uptake of RCPTN by HepG2 and HCa-F cells was analyzed using confocal laser scanning microscopy. Apoptosis was induced in HepG2 cells by RPTN, RBG solution (RS), and 5 fluorouracil solution (used as the negative controls), as assayed using flow cytometry. LD50 (median lethal dose) values were determined for RS and RPTN, and the liver-targeting properties were determined for RCPTN in intravenously injected mice. A pharmacokinetic study was conducted in rats, and the in vivo therapeutic effects of RPTN, RPN, and RS were examined in a mouse tumor model. The results showed that RCPTN simultaneously delivered both coumarin-6 and RBG into HepG2 and HCa-F cells. The ratio of apoptotic cells was increased in the RPTN group. The LD50 for RPTN was 2.02-fold higher than the value for RS. Compared to RS, RPTN and RPN both showed a significant difference in vivo not only in the pharmacodynamic study but also in anticancer efficacy, and RPTN performed much better than RPN. The detection indexes for drug concentration and fluorescence inversion microscopy images both demonstrated that RCPTN was much better at targeting the liver than RS. The liver-targeting RPTN, which displayed enhanced pharmacological effects and decreased toxicity for the loaded drug RBG, is therefore a promising intravenous dosage form that may be useful in the treatment of liver cancer. PMID- 26869791 TI - Mania following ketamine abuse. AB - Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, has multiple clinical uses. On the other hand, ketamine abuse or recreational use has been gaining increasing attention. Induction of mania and psychotic symptoms has been reported in a patient receiving IV ketamine therapy for reflex sympathetic dystrophy. We here report a 26 year-old man who abused ketamine by inhalation for 12 months and developed manic-like symptoms after ketamine use. This case suggests a possible relationship between manic symptoms and ketamine abuse. To the best of our knowledge, this may be the first report regarding mania after recreational use of ketamine. PMID- 26869790 TI - Examining Dark Triad traits in relation to mental toughness and physical activity in young adults. AB - OBJECTIVE: The Dark Triad (DT) describes a set of three closely related personality traits: Machiavellianism, narcissism, and psychopathy. Mental toughness (MT) refers to a psychological construct combining confidence, commitment, control, and challenge. High MT is related to greater physical activity (PA) and, relative to men, women have lower MT scores. The aims of the present study were 1) to investigate the association between DT, MT, and PA, and 2) to compare the DT, MT, and PA scores of men and women. METHODS: A total of 341 adults (M=29 years; 51.6% women; range: 18-37 years) took part in the study. Participants completed a series of questionnaires assessing DT, MT, and PA. RESULTS: Machiavellianism, narcissism, and psychopathy were all significantly associated with higher MT scores (rs =0.45, 0.50, and 0.20, respectively). DT traits and MT were associated with more vigorous PA. Compared to men, women participants had lower scores for DT traits (overall score and psychopathy), while no differences were found for MT or PA in both sexes. CONCLUSION: DT traits, high MT, and vigorous PA are interrelated. This pattern of results might explain why, for instance, successful professional athletes can at the same time be tough and ruthless. PMID- 26869792 TI - Electroencephalogram characteristics in patients with chronic fatigue syndrome. AB - OBJECTIVE: To explore the electroencephalogram (EEG) characteristics in patients with chronic fatigue syndrome (CFS) using brain electrical activity mapping (BEAM) and EEG nonlinear dynamical analysis. METHODS: Forty-seven outpatients were selected over a 3-month period and divided into an observation group (24 outpatients) and a control group (23 outpatients) by using the non-probability sampling method. All the patients were given a routine EEG. The BEAM and the correlation dimension changes were analyzed to characterize the EEG features. RESULTS: 1) BEAM results indicated that the energy values of delta, theta, and alpha1 waves significantly increased in the observation group, compared with the control group (P<0.05, P<0.01, respectively), which suggests that the brain electrical activities in CFS patients were significantly reduced and stayed in an inhibitory state; 2) the increase of delta, theta, and alpha1 energy values in the right frontal and left occipital regions was more significant than other encephalic regions in CFS patients, indicating the region-specific encephalic distribution; 3) the correlation dimension in the observation group was significantly lower than the control group, suggesting decreased EEG complexity in CFS patients. CONCLUSION: The spontaneous brain electrical activities in CFS patients were significantly reduced. The abnormal changes in the cerebral functions were localized at the right frontal and left occipital regions in CFS patients. PMID- 26869789 TI - Local delivery of controlled-release simvastatin to improve the biocompatibility of polyethylene terephthalate artificial ligaments for reconstruction of the anterior cruciate ligament. AB - The Ligament Advanced Reinforcement System has recently been widely used as the primary graft of choice in anterior cruciate ligament (ACL) reconstruction. But the biological graft-bone healing still remains a problem. Previous studies have shown that simvastatin (SIM) stimulates bone formation. The objective of this study was to investigate whether surface coating with collagen containing low dose SIM microsphere could enhance the surface biocompatibility of polyethylene terephthalate (PET) artificial ligaments to accelerate graft-to-bone healing. The in vitro studies demonstrated that bone marrow stromal cells on the collagen coated PET scaffolds (COL/PET) and simvastatin/collagen-coated PET scaffolds (SIM/COL/PET) proliferated vigorously. Compared with the PET group and the COL/PET group, SIM could induce bone marrow stromal cells' osteoblastic differentiation, high alkaline phosphatase activity, more mineralization deposition, and more expression of osteoblast-related genes, such as osteocalcin, runt-related transcription factor 2, bone morphogenetic protein-2, and vascular endothelial growth factor, in the SIM/COL/PET group. In vivo, rabbits received ACL reconstruction with different scaffolds. Histological analysis demonstrated that graft-bone healing was significantly greater with angiogenesis and osteogenesis in the SIM/COL/PET group than the other groups. In addition, biomechanical testing at the eighth week demonstrated a significant increase in the ultimate failure load and stiffness in the SIM/COL/PET group. The low dose of SIM-sustained release from SIM/COL/PET promoted the graft-bone healing via its effect on both angiogenesis and osteogenesis. This study suggested that collagen containing low-dose SIM microsphere coating on the surface of PET artificial ligaments could be potentially applied for ACL reconstruction. PMID- 26869793 TI - Safety and efficacy of incobotulinumtoxinA as a potential treatment for poststroke spasticity. AB - Spasticity is a common disabling symptom for several neurological conditions. Botulinum toxin type A injection represents the gold standard treatment for focal spasticity after stroke showing efficacy, reversibility, and low prevalence of complications. In recent years, incobotulinumtoxinA, a new Botulinum toxin type A free of complexing proteins, has been used for treating several movement disorders with safety and efficacy. IncobotulinumtoxinA is currently approved for treating spasticity of the upper limb in stroke survivors, even if several studies described the use also in lower limb muscles. In the present review article, we examine the safety and effectiveness of incobotulinumtoxinA for the treatment of spasticity after stroke. PMID- 26869794 TI - A new modified technique of laparoscopic needle catheter jejunostomy: a 2-year follow-up study. AB - BACKGROUND: The aim of this study was to establish a modified technique for performing laparoscopic needle catheter jejunostomy. METHODS: From May 2011 to October 2013, laparoscopic needle catheter jejunostomy was performed in 21 patients with esophageal cancer. During the procedure, jejunal inflation was performed via a percutaneous 20-gauge intravenous catheter to facilitate the subsequent puncture of the jejunal wall by the catheter needle. The success rate, procedure time, complications, and short-term outcomes were evaluated. RESULTS: All laparoscopic needle catheter jejunostomies were technically successful, with no perioperative mortality or conversion to a laparotomy. The operation required a mean time of 51.4+/-14.2 (range 27-80) minutes, and operative bleeding range was 5-20 mL. There was one reoperation required for one patient on postoperative day 5, because the feeding tube was accidentally pulled out during sleep, by patient himself, and the second laparoscopic jejunostomy for this patient was performed successfully. One patient had puncture site pain and was successfully treated with oral analgesics. Other complications, such as gastrointestinal bleeding, intestinal perforation, intestinal obstruction, tube dysfunction, pericatheter leakage, and infection at the skin insertion site, were not observed. The 30-day mortality rate was 4.8% (one out of 21), which was not attributed to the procedure. Enteral nutrition was gradually administered 24-48 hours after operation. CONCLUSION: The novel modified technique of laparoscopic needle catheter jejunostomy is a technically feasible, with a high technical success rate and low complication rate. Its specific advantage is simplicity and safety, and this modified approach can be considered for routine clinical use after long-term outcome evaluation. PMID- 26869796 TI - Facebook as a tool for communication, collaboration, and informal knowledge exchange among members of a multisite family health team. AB - OBJECTIVE: To implement and evaluate a private Facebook group for members of a large Ontario multisite Family Health Team (FHT) to facilitate improved communication and collaboration. DESIGN: Program implementation and subsequent survey of team members. SETTING: A large multisite FHT in Toronto, Ontario. PARTICIPANTS: Health professionals of the FHT. MAIN OUTCOME MEASURES: Usage patterns and self-reported perceptions of the Facebook group by team members. RESULTS: At the time of the evaluation survey, the Facebook group had 43 members (37.4% of all FHT members). Activity in the group was never high, and posts by team members who were not among the researchers were infrequent throughout the study period. The content of posts fell into two broad categories: 1) information that might be useful to various team members and 2) questions posed by team members that others might be able to answer. Of the 26 team members (22.6%) who completed the evaluation survey, many reported that they never logged into the Facebook page (16 respondents), and never used it to communicate with team members outside of their own site of practice (19 respondents). Only six respondents reported no concerns with using Facebook as a professional communication tool; the most frequent concerns were regarding personal and patient privacy. CONCLUSION: The use of social media by health care practitioners is becoming ubiquitous. However, the issues of privacy concerns and determining how to use social media without adding to provider workload must be addressed to make it a useful tool in health care. PMID- 26869797 TI - Oct-4 is associated with gastric cancer progression and prognosis. AB - AIM: To investigate the clinical significance of Oct-4 in the development and progression of gastric cancer. METHODS: Immunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues. RESULTS: Positive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5 year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer. CONCLUSION: Oct-4 protein is a useful marker in predicting tumor progression and prognosis. PMID- 26869795 TI - A critical appraisal of paliperidone long-acting injection in the treatment of schizoaffective disorder. AB - Schizoaffective disorder (SCA) is a chronic and disabling mental illness that presents with mixed symptoms of schizophrenia and affective disorders. SCA is recognized as a discrete disorder, but with greater heterogeneity and symptom overlap, leading to difficulty and delay in diagnosis. Although the overall prognosis is intermediate between schizophrenia and mood disorders, SCA is associated with higher rates of suicide and hospitalization than schizophrenia. No treatment guidelines exist for SCA, and treatment is frequently complex, involving off-label use and polypharmacy (typically combinations of antipsychotics, mood stabilizers, and antidepressants). Oral paliperidone extended-release was the first agent to be approved for the treatment of SCA. As in schizophrenia and bipolar disorder, adherence to oral medications is poor, further contributing to suboptimal outcomes. The use of an antipsychotic in a long-acting injection (LAI) addresses adherence issues, thus potentially reducing relapse. Paliperidone palmitate represents the LAI formulation of paliperidone. In a long-term, double-blind, randomized, controlled trial of adult patients (n=334; intent-to-treat [ITT]) with SCA, paliperidone long-acting injection (PLAI) significantly delayed risk of relapse compared to placebo (hazard ratio 2.49, 95% confidence interval, 1.55-3.99; P<0.001). This study demonstrated the efficacy and safety of PLAI when used as either monotherapy or adjunctive therapy for the maintenance treatment of SCA. The results are consistent with a similarly designed study conducted in patients with schizophrenia, which suggests a benefit in the long-term control of not only psychotic but also affective symptoms. No new safety signals were observed. When used in monotherapy, PLAI simplifies treatment by reducing complex pharmacotherapy and obviating the necessity for daily oral medications. PLAI is the second agent, and the first LAI, to be approved for the treatment of SCA; as an LAI formulation, there is the advantage of improved adherence and simplified treatment in the long-term management of SCA. PMID- 26869798 TI - Conservative treatment of coexisting microinvasive squamous and adenocarcinoma of the cervix: report of two cases and literature review. AB - Coexistence of microinvasive squamous cell carcinoma (MISCC) and microinvasive adenocarcinoma (MIAC) of the cervix is a rare phenomenon with very few clinically significant cases described in the literature. While a conservative approach has been studied, and may be effective in MISCC, a lower number of studies that recommend conservative treatment are available for MIAC. We report two cases of synchronous cervix lesions in two separate foci, MISCC and MIAC, who underwent fertility-sparing treatment with long-term follow-up. We describe clinical, histological, and immunohistochemical features of the two cases. The first case is a 41-year-old female with a diagnosis of MIAC of endocervical type, grade 1 differentiation, with a stromal invasion, associated with a separate area of squamous cell carcinoma (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). The second case is a 45-year-old female with a diagnosis of plurifocal MISCC, associated with an MIAC of endocervical type with a stromal invasion (International Federation of Gynecology and Obstetrics/TNM stage: pT1a1G1). After multidisciplinary counseling, both patients accepted conization as definitive treatment. Eleven years after the conization, all tests (Papanicolaou smear, colposcopy, cervical curettage, and hybrid capture 2-human papillomavirus test) planned quarterly in the first year and every 6 months in the subsequent years were negative in both patients. In women affected by stage IA1 squamous cervical cancer coexisting with stage IA1 adenocarcinoma endocervical type, with clear margins, and without lymphovascular space invasion, cervical conization may be considered a fertility-preserving, safe, and definitive therapeutic option. PMID- 26869799 TI - Immunocompromised and immunocompetent mouse models for head and neck squamous cell carcinoma. AB - Mouse models can closely mimic human oral squamous epithelial carcinogenesis, greatly expand the in vivo research possibilities, and play a critical role in the development of diagnosis, monitoring, and treatment of head and neck squamous cell carcinoma. With the development of the recent research on the contribution of immunity/inflammation to cancer initiation and progression, mouse models have been divided into two categories, namely, immunocompromised and immunocompetent mouse models. And thus, this paper will review these two kinds of models applied in head and neck squamous cell carcinoma to provide a platform to understand the complicated histological, molecular, and genetic changes of oral squamous epithelial tumorigenesis. PMID- 26869800 TI - Biomarkers predicting resistance to epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer with wild-type KRAS. AB - EGFR pathway is an important therapeutic target in human tumors, including metastatic colorectal cancer (mCRC). The advent of EGFR-targeted monoclonal antibodies panitumumab and cetuximab has generated promise for the treatment of mCRC and has largely improved patients' progression-free survival (PFS) and overall survival (OS). However, treatment with anti-EGFR monoclonal antibodies is only effective in a subset of mCRC patients with wild-type KRAS. This indicates that there are other factors affecting the efficacy of anti-EGFR monoclonal antibodies. Existing studies have demonstrated that among colorectal cancer patients with wild-type KRAS, harboring mutations of BRAF, PIK3CA, NRAS, or PTEN null may demonstrate resistance to anti-EGFR-targeted therapy, and biomarkers detection can provide better-personalized treatment for mCRC patients. How to identify and reverse the secondary resistance to anti-EGFR monoclonal antibody therapy is also another great challenge to improve the anti-EGFR efficacy in wild type KRAS mCRC patients. Finally, both of the molecular mechanisms of response and acquired resistance would be important for the directions of future research. This review focuses on how to further improve the predictive value of anti-EGFR therapies and how to also try and avoid futile treatment for wild-type KRAS colorectal cancer patients. PMID- 26869802 TI - Correlation between XRCC1 Arg399Gln genetic polymorphisms and susceptibility to bladder cancer: a meta-analysis. AB - The relationship between XRCC1 polymorphisms and bladder cancer has been widely studied. Here, our meta-analysis was conducted to evaluate the correlations between common genetic polymorphisms in XRCC1 and susceptibility to bladder cancer. In order to derive a more precise estimation of the association, 27 clinical case-control studies (which met all the inclusion criteria) were included in this meta-analysis. A total of 8,539 cancer cases and 10,750 controls were involved in this meta-analysis. Overall, no significant association was detected in allelic model (A allele vs T allele odds ratio [OR] =0.87, 95% confidence interval [CI], 0.71-1.06), homozygote comparison (AA vs GG OR =1.12, 95% CI, 0.68-1.85), heterozygote comparison (AT vs TT OR =1.01, 95% CI, 0.81 1.26), dominant model (AA + AG vs GG OR =0.93, 95% CI, 0.85-1.02), and recessive model (AA vs AG + GG OR =1.01, 95% CI, 0.88-1.15), but a moderately significant association was found for AG vs GG (OR =0.241, 95% CI =0.17-0.35). Subgroup analysis based on ethnicity. Ethnicity analysis suggested that genetic polymorphisms in XRCC1 were not correlated with increased bladder cancer risk among Asians (all P>0.05). Therefore, we concluded that XRCC1 genetic polymorphism may not contribute to bladder cancer susceptibility in the present meta-analysis, and further well-designed studies with a large sample size are warranted to validate our conclusion. PMID- 26869801 TI - Association between interleukin-6 polymorphisms and urinary system cancer risk: evidence from a meta-analysis. AB - BACKGROUND: Interleukin-6 (IL-6) is a multifunctional proinflammatory cytokine involved in cancer initiation and progression. Numerous studies have investigated the associations between IL-6 polymorphisms (IL-6 -174G>C, -592G>C, -597G>A) and risk of urinary system cancers, including prostate cancer, bladder cancer, and renal cell cancer. However, conclusions from these studies were controversial. Thus, we conducted the current meta-analysis to obtain the comprehensive profile regarding the association between IL-6 polymorphisms and urinary system cancer risk. METHODS: According to inclusion and exclusion criteria, the associations of IL-6 polymorphisms with urinary system cancer were searched from database and analyzed using STATA 12.0 statistical software. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: A total of 20 previous publications consisting of 15,033 cases and 17,655 controls were involved in this meta-analysis. Significant association was observed in overall population regarding IL-6 -592G>C polymorphisms (G vs C: OR =0.1.30, 95% CI =1.13-2.52; GG vs CC: OR =1.81, 95% CI =1.31-2.52; GG vs GC + CC: OR =1.33, 95% CI =1.02-1.75; GG + GC vs CC: OR =1.41, 95% CI =1.09-1.83). In the stratified analyses by ethnicity, the significant associations were found among Asian (GG vs CC: OR =1.89, 95% CI =1.34-2.66; GG + GC vs CC: OR =1.43, 95% CI =1.09-1.87) and Black population (GC vs CC: OR =0.20, 95% CI =0.05-0.82) rather than Caucasian men. Likewise, there were noticeable associations in almost all the other subanalyses such as cancer types, control sources, genotyped methods, and sample sizes. However, no significant associations were identified between any of IL-6 -174G>C polymorphisms with urinary system cancer, except for Asian population (G vs C: OR =0.81, 95% CI =0.70-0.95; GG vs CC: OR =0.51, 95% CI =0.35 0.74; GC vs CC: OR =0.49, 95% CI =0.33-0.72; GG + GC vs CC: OR =0.50, 95% CI =0.35-0.72; respectively). In addition, no significant associations were detected between IL-6 -597G>A polymorphism and urinary system cancer, regardless of whole or subgroups. CONCLUSION: This meta-analysis presents a relatively comprehensive view of the associations between IL-6 polymorphism and urinary system cancer risk to explore the carcinogenic mechanisms, which will help shed light on the clinical diagnosis and therapy for urinary system cancer. However, further detailed studies are needed to verify our conclusion. PMID- 26869803 TI - Long-term outcomes of different bortezomib-based regimens in Chinese myeloma patients. AB - Bortezomib has significantly increased the response rates in multiple myeloma (MM), but optimal bortezomib-based regimens for initial MM therapy have not yet been defined. We retrospectively compared the outcomes of 128 patients newly diagnosed with symptomatic MM who received either bortezomib combined with dexamethasone (PD) or three-drug combinations of PD with liposomal doxorubicin (PAD) or thalidomide (PTD). The overall response rate (ORR), very good partial response (VGPR) rate, and complete remission CR/near-complete remission (nCR) results were better for the PAD and PTD regimens than for the PD group. Three year overall survival (OS) was 80.1%, 72.5%, and 61.8% with PAD, PTD, and PD regimens, respectively. The 3-year OS rate of PAD and PTD was significantly higher than that of PD (80.1% vs 61.8%, P=0.024; 72.5% vs 61.8%, P=0.035), but the difference was not statistically significant between PAD and PTD (80.1% vs 72.5%, P=0.843). Similarly, the PAD and PTD regimens resulted in significantly superior 3-year progression-free survival (PFS) rates. The patients in the PTD arm were more frequently observed with grade 1-3 peripheral neuropathy (PN), compared to those in the PAD and PD groups, especially grade 2-3 PN. PN developed less frequently without sacrificing the efficacy when bortezomib was administered subcutaneously rather than intravenously. Our experience suggests that the three drug combinations PAD and PTD produce a better outcome than PD, especially with respect to PAD, with fewer adverse events. PMID- 26869804 TI - Advances in dosimetry and biological predictors of radiation-induced esophagitis. AB - OBJECTIVE: To summarize the research progress about the dosimetry and biological predictors of radiation-induced esophagitis. METHODS: We performed a systematic literature review addressing radiation esophagitis in the treatment of lung cancer published between January 2009 and May 2015 in the PubMed full-text database index systems. RESULTS: Twenty-eight eligible documents were included in the final analysis. Many clinical factors were related to the risk of radiation esophagitis, such as elder patients, concurrent chemoradiotherapy, and the intense radiotherapy regimen (hyperfractionated radiotherapy or stereotactic body radiotherapy). The parameters including Dmax, Dmean, V20, V30, V50, and V55 may be valuable in predicting the occurrence of radiation esophagitis in patients receiving concurrent chemoradiotherapy. Genetic variants in inflammation-related genes are also associated with radiation-induced toxicity. CONCLUSION: Dosimetry and biological factors of radiation-induced esophagitis provide clinical information to decrease its occurrence and grade during radiotherapy. More prospective studies are warranted to confirm their prediction efficacy. PMID- 26869805 TI - Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study. AB - OBJECTIVE: The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. METHODS: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. RESULTS: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan-Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P-value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and progression in the cohort. CONCLUSION: Intravenous chemotherapy combined with intravesical chemotherapy offers a better oncologic outcome than the intravesical chemotherapy alone for patients with T1G3 bladder urothelial carcinoma after TURBT, and it may be considered as a new therapy strategy for T1G3 bladder cancer. PMID- 26869806 TI - Examination of hospital length of stay in Canada among patients with acute bacterial skin and skin structure infection caused by methicillin-resistant Staphylococcus aureus. AB - PURPOSE: Skin infections, particularly those caused by resistant pathogens, represent a clinical burden. Hospitalization associated with acute bacterial skin and skin structure infections (ABSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) is a major contributor to the economic burden of the disease. This study was conducted to provide current, real-world data on hospitalization patterns for patients with ABSSSI caused by MRSA across multiple geographic regions in Canada. PATIENTS AND METHODS: This retrospective cohort study evaluated length of stay (LOS) for hospitalized patients with ABSSSI due to MRSA diagnosis across four Canadian geographic regions using the Discharge Abstract Database. Patients with ICD-10-CA diagnosis consistent with ABSSSI caused by MRSA between January 2008 and December 2014 were selected and assigned a primary or secondary diagnosis based on a prespecified ICD-10-CA code algorithm. RESULTS: Among 6,719 patients, 3,273 (48.7%) and 3,446 (51.3%) had a primary and secondary diagnosis, respectively. Among patients with a primary or secondary diagnosis, the cellulitis/erysipelas subtype was most common. The majority of patients presented with 0 or 1 comorbid condition; the most common comorbidity was diabetes. The mean LOS over the study period varied by geographic region and year; in 2014 (the most recent year analyzed), LOS ranged from 7.7 days in Ontario to 13.4 days in the Canadian Prairie for a primary diagnosis and from 18.2 days in Ontario to 25.2 days in Atlantic Canada for a secondary diagnosis. A secondary diagnosis was associated with higher rates of continuing care compared with a primary diagnosis (10.6%-24.2% vs 4.6%-12.1%). CONCLUSION: This study demonstrated that the mean LOS associated with ABSSSI due to MRSA in Canada was minimally 7 days. Clinical management strategies, including medication management, which might facilitate hospital discharge, have the potential to reduce hospital LOS and related economic burden associated with ABSSSI caused by MRSA. PMID- 26869807 TI - Assessment of vitamin D levels in newly diagnosed children with type 1 diabetes mellitus comparing two methods of measurement: a facility's experience in the Middle Eastern country of Bahrain. AB - BACKGROUND: The number of children being diagnosed with type 1 diabetes mellitus (T1DM) is on the rise and has more than doubled in the past 10 years in Bahrain. Some studies have linked low vitamin D levels with an increased risk of diabetes. There are concerns regarding the variations in circulating 25(OH)D levels measured by different laboratories and by using different analytical techniques. OBJECTIVE: The aim of this study was to evaluate the vitamin D levels of newly diagnosed children with T1DM using the "gold standard method" with high-pressure liquid chromatography-tandem mass spectrometry methods compared to the chemiluminescence micro-particle immunoassay (CMIA) used in a hospital laboratory. SUBJECTS: Eighteen children, aged 6-12 years, who received a confirmed diagnosis of T1DM in 2014 were chosen as subjects. METHODS: Serum vitamin D levels were assessed in a hospital, while an extra aliquot of blood collected during routine blood collection after acquiring informed written consents from the subjects, and sent to Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders to be analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The mean age of the study group was 9+/-2 years. The mean total of 25(OH)D levels (D3 and D2) assessed by UPLC-MS/MS was 49.7+/-18.8, whereas the mean total of 25(OH)D levels obtained from the CMIA assay was 44.60+/-13.20. The difference in classification between the two methods was found to be statistically significant (P=0.004). A Bland-Altman plot showed a poor level of agreement between the two assay methods. The CMIA overestimated insufficient values and underestimated deficiency, when compared to UPLC-MS/MS. CONCLUSION: There was a statistically significant difference between the two assay methods with CMIA overestimating vitamin D insufficiency. Clinicians should be prudent in their assessment of a single vitamin D reading, when the gold standard method is not available or feasible. PMID- 26869809 TI - Terminology of chronic pain: the need to "level the playing field". PMID- 26869808 TI - Fecal calprotectin in inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) and irritable bowel syndrome share many symptoms. While irritable bowel syndrome is a functional bowel disorder for which no specific treatment is available, the range of effective therapies for IBD is evolving rapidly. Accurate diagnosis of IBD is therefore essential. Clinical assessment, together with various imaging modalities and endoscopy, has been the mainstay of diagnosis for many years. Fecal biomarkers of gastrointestinal inflammation have appeared in the past decade, of which calprotectin, a neutrophil cytosolic protein, has been studied the most. Crohn's disease and ulcerative colitis are chronic remitting and relapsing diseases, and objective assessment of disease activity and response to treatment are important. This review focuses on the use of fecal calprotectin measurements in the diagnosis and monitoring of patients with IBD. PMID- 26869810 TI - Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension. AB - The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH). Intravenous (IV) epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is great interest in the development of an oral prostacyclin analog that could mimic the benefits of IV therapy. Herein, we highlight the development of oral prostacyclin therapy, focusing on oral treprostinil, the only US Food and Drug Administration approved oral prostacyclin. Recent Phase III clinical trials have shown the drug to improve exercise tolerance in treatment-naive PAH patients, but not patients on background oral therapy. Oral treprostinil appears to be most efficacious at higher doses, but its side effect profile and complexities with dosing complicate its use. While oral treprostinil's current therapeutic role in PAH remains unclear, ongoing studies of this class of medication should help clarify their role in the treatment of PAH. PMID- 26869811 TI - The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial. AB - BACKGROUND: Hypertension affects 30% of adults worldwide. Garlic supplements have shown promise in the treatment of uncontrolled hypertension, and the mechanism of action is biologically plausible. Our trial is the first to assess the effect of aged garlic extract on central blood pressure and arterial stiffness, regarded as important risk factors for cardiovascular morbidity. SUBJECTS AND METHODS: A total of 88 general practice patients and community members with uncontrolled hypertension completed a double-blind randomized placebo-controlled trial of 12 weeks investigating the effect of daily intake of aged garlic extract (1.2 g containing 1.2 mg S-allylcysteine) or placebo on blood pressure, and secondary outcome measures of central-hemodynamics and other cardiovascular markers, including cholesterol, homocysteine, platelet function, and inflammatory markers. RESULTS: Mean blood pressure was significantly reduced by 5.0+/-2.1 mmHg (P=0.016) systolic, and in responders by 11.5+/-1.9 mmHg systolic and 6.3+/-1.1 mmHg diastolic compared to placebo (P<0.001). Central hemodynamic-measures tended to improve in the garlic group more than in the placebo group, including central blood pressure, central pulse pressure, mean arterial pressure, augmentation pressure, pulse-wave velocity, and arterial stiffness. While changes in other cardiovascular markers did not reach significance due to small numbers in subgroups with elevated levels, trends in beneficial effects of garlic on the inflammatory markers TNFalpha, total cholesterol, low-density lipid cholesterol, and apolipoproteins were observed. Aged garlic extract was highly tolerable and acceptable, and did not increase the risk of bleeding in patients on blood thinning medication. CONCLUSION: Our trial suggests that aged garlic extract is effective in reducing peripheral and central blood pressure in a large proportion of patients with uncontrolled hypertension, and has the potential to improve arterial stiffness, inflammation, and other cardiovascular markers in patients with elevated levels. Aged garlic extract was highly tolerable with a high safety profile as a stand-alone or adjunctive antihypertensive treatment. PMID- 26869812 TI - Chronic resveratrol reverses a mild angiotensin II-induced pressor effect in a rat model. AB - Resveratrol is reported to reduce blood pressure in animal models of hypertension, but the mechanisms are unknown. We have shown that resveratrol infusion increases sodium excretion. We hypothesized that chronic ingestion of resveratrol would reduce angiotensin II (Ang II)-induced increases in blood pressure by decreasing oxidative stress and by also decreasing sodium reabsorption through a nitric oxide-dependent mechanism. We infused rats with vehicle or 80 MUg Ang II/d over 4 weeks. Vehicle or Ang II-infused rats were individually housed, pair fed, and placed on a diet of normal chow or normal chow plus 146 mg resveratrol/d. Groups included 1) control, 2) resveratrol-fed, 3) Ang II-treated, and 4) Ang II plus resveratrol. Systolic blood pressure was measured by tail cuff. During the 4th week, rats were placed in metabolic caging for urine collection. NO2/NO3 and 8-isoprostane excretion were measured. Ang II increased systolic blood pressure in the 1st week by +14+/-5 mmHg (P<0.05) in Group 3 and +10+/-3 mmHg (P<0.05) in Group 4, respectively. Blood pressure was unchanged in Groups 1 and 2. After 4 weeks, blood pressure remained elevated in Group 3 rats with Ang II (+9+/-3 mmHg, P<0.05), but in Group 4, blood pressure was no longer elevated (+2+/-2 mmHg). We found no significant differences between the groups in sodium excretion or cumulative sodium balance (18.49+/-0.12, 17.75+/-0.16, 17.97+/-0.17, 18.46+/-0.18 MUEq Na+/7 d in Groups 1-4, respectively). Urinary excretion of NO2/NO3 in the four groups was 1) 1631+/-207 MUmol/24 h, 2) 1045+/ 236 MUmol/24 h, 3) 1490+/-161 MUmol/24 h, and 4) 609+/-17 MUmol/24 h. 8 Isoprostane excretion was 1) 63.85+/-19.39 nmol/24 h, 2) 73.57+/-22.02 nmol/24 h, 3) 100.69+/-37.62 nmol/24 h, and 4) 103.00+/-38.88 nmol/24 h. We conclude that chronic resveratrol supplementation does not blunt Ang II-increased blood pressure, and while resveratrol has mild depressor effects, these do not seem to be due to natriuresis or enhanced renal nitric oxide synthesis. PMID- 26869813 TI - The COLOFOL trial: study design and comparison of the study population with the source cancer population. AB - INTRODUCTION: The COLOFOL trial, a prospective randomized multicenter trial comparing two follow-up regimes after curative surgical treatment for colorectal cancer, focuses on detection of asymptomatic recurrences. This paper aims to describe the design and recruitment procedure in the COLOFOL trial, comparing demographic characteristics between randomized patients and eligible patients not included in the study. MATERIALS AND METHODS: COLOFOL was designed as a pragmatic trial with wide inclusion criteria and few exclusion criteria, in order to obtain a sample reflecting the general patient population. To be eligible, patients had to be 75 years or younger and curatively resected for stage II or III colorectal cancer. Exclusion criteria were hereditary colorectal cancer, no signed consent, other malignancy, and life expectancy less than 2 years due to concomitant disease. In four of the 24 participating centers, we scrutinized hospital inpatient data to identify all colorectal cancer patients who underwent surgery, in order to ascertain all eligible patients who were not included in the study and to compare them with enrolled patients. RESULTS: Of a total of 4,445 eligible patients, 2,509 patients were randomized (56.4% inclusion rate). A total of 1,221 eligible patients were identified in the scrutinized hospitals, of which 684 (56%) were randomized. No difference in age or sex distribution was observed between randomized and nonrandomized eligible patients. However, a difference was noted in tumor location and stage distribution, with 5.6% more patients in the randomized group having colon cancer and 6.7% more patients having stage II disease. CONCLUSION: Patients in the two study arms were not only demographically similar, but also similar to nonincluded eligible patients, apart from stage and localization. The analyses will be stratified by these variables. Taken together, we conclude that our trial results will be robust and possible to extrapolate to the target population. PMID- 26869814 TI - Prevalence and risk factors of gestational diabetes mellitus in Yemen. AB - PURPOSE: Gestational diabetes mellitus (GDM) continues to be a significant health disorder triggering harmful complications in pregnant women and fetuses. Our knowledge of GDM epidemiology in Yemen is largely based on very limited data. The aim of this study was, therefore, to determine the prevalence and risk factors of GDM among pregnant women in Dhamar governorate, Yemen. PATIENTS AND METHODS: A total of 311 subjects were randomly selected for this cross sectional survey. Health history data and blood samples were collected using a pretested questionnaire. To determine the prevalence of GDM, the fasting and random blood glucose techniques were applied according to the recommendations of the American Diabetes Association, using alternative methods that are more convenient to the targeted population. Poisson's regression model incorporating robust sandwich variance was utilized to assess the association of potential risk factors in developing GDM. RESULTS: The prevalence of GDM was found to be 5.1% among the study population. Multivariate analysis confirmed age >=30 years, previous GDM, family history of diabetes, and history of polycystic ovary syndrome as independent risk factors for GDM prevalence. However, body mass index >=30 kg/m(2) and previous macrosomic baby were found to be dependent risk factors. CONCLUSION: This study reports new epidemiological information about the prevalence and risk factors of GDM in Yemen. Introduction of proper maternal and neonatal medical care and health education are important in order to save the mother and the baby. PMID- 26869815 TI - Amniotic membrane-assisted trabeculectomy for refractory glaucoma with corneal disorders. AB - PURPOSE: To report the cases of six consecutive patients who underwent amniotic membrane (AM)-assisted trabeculectomy (TLE) to treat refractory glaucoma with severe corneal disorders. METHODS: This study involved six patients (three males and three females, mean age: 69.5+/-15.8 years) with refractory glaucoma and severe corneal disorders. The surgical procedure for each patient involved trabecular tissue being excised, and human AM then being placed epithelial side up on the corneal surface, sutured at the limbal sclera, and flipped over onto the sclera to cover the TLE area. The remaining edge of the AM was then inserted into the subconjunctival space and sutured. Medical records of all cases were reviewed with regard to intraocular pressure (IOP), visual acuity, and condition of the filtering bleb and ocular surface. RESULTS: The mean observation period was 69.5+/-15.8 months, and mean IOP at presurgery and at 1, 3, and 7 years postoperative was 40.3+/-6.9, 23.0+/-12.1, 25.6+/-12.8, and 28.5+/-19.1 mmHg, respectively. Glaucoma medications decreased from 3.0+/-1.1 drugs (presurgery) to 0.8+/-1.0 drugs (7 years postoperative). However, in some cases, ocular surface conditions or visual acuity worsened during the follow-up period. CONCLUSION: Using AM as an internal patch for TLE, moderately good IOP control was obtained initially for the refractory glaucoma with severe corneal disorders; however, ocular surface conditions required special care, and the long-term IOP control was limited in some cases. PMID- 26869816 TI - Good outcomes in a patient with a Duret hemorrhage from an acute subdural hematoma. AB - BACKGROUND: Secondary brain stem injury is associated with transtentorial herniation, and manifests as "Duret" hemorrhages. Such an injury has been considered a terminal brain stem event with a high morbidity and mortality, sometimes discouraging continuation of care. However, there have been rare instances where patients have had reasonable recovery. We report another case, emphasizing that such an injury by itself should not deter aggressive measures, as good outcomes remain a possibility. CASE PRESENTATION: A 37-year-old male sustained a right subdural hematoma after a mechanical fall while intoxicated. He presented initially with a Glasgow Coma Scale 15. Three days later, he exhibited acute neurological deterioration to Glasgow Coma Scale 4, requiring intubation and mannitol. Repeat scan demonstrated enlarging right subdural hematoma with worsening shift; brain stem hemorrhage was noted at pontomesencephalic junction. Patient was immediately taken for subdural hematoma evacuation. The following day, patient was able to sluggishly follow commands in all four extremities. He had a short stay for inpatient rehabilitation and underwent autologous cranioplasty at 3 months. On examination, he was awake, alert, and oriented to self, time, and location; he exhibited dysarthric speech, right ptosis, but followed commands in all four extremities with no focal motor weakness. CONCLUSION: In contrast to the common belief, patients suffering from a "Duret" hemorrhage can still have a good outcome. "Duret" hemorrhages may not represent a fatal injury. The finding from this paper suggests the finding of "Duret" hemorrhages on imaging should not deter aggressive measures especially in patients with lesions causing significant mass effects. Overall clinical status should drive surgical options and clinical course. PMID- 26869817 TI - Chronic sleep disturbance and neural injury: links to neurodegenerative disease. AB - Sleep-wake disruption is frequently observed and often one of the earliest reported symptoms of many neurodegenerative disorders. This provides insight into the underlying pathophysiology of these disorders, as sleep-wake abnormalities are often accompanied by neurodegenerative or neurotransmitter changes. However, in addition to being a symptom of the underlying neurodegenerative condition, there is also emerging evidence that sleep disturbance itself may contribute to the development and facilitate the progression of several of these disorders. Due to its impact both as an early symptom and as a potential factor contributing to ongoing neurodegeneration, the sleep-wake cycle is an ideal target for further study for potential interventions not only to lessen the burden of these diseases but also to slow their progression. In this review, we will highlight the sleep phenotypes associated with some of the major neurodegenerative disorders, focusing on the circadian disruption associated with Alzheimer's disease, the rapid eye movement behavior disorder and sleep fragmentation associated with Parkinson's disease, and the insomnia and circadian dysregulation associated with Huntington's disease. PMID- 26869818 TI - Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder. AB - INTRODUCTION: Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. METHODS: Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants' brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5-16 Hz) and slow-frequency spindle activity (10.5-12.5 Hz). RESULT: Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. CONCLUSION: Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep. PMID- 26869819 TI - Urology - a specialty that will be faced by all future doctors. PMID- 26869820 TI - Chemical diversity of ginseng saponins from Panax ginseng. AB - Ginseng, a perennial plant belonging to the genus Panax of the Araliaceae family, is well known for its medicinal properties that help alleviate pathological symptoms, promote health, and prevent potential diseases. Among the active ingredients of ginseng are saponins, most of which are glycosides of triterpenoid aglycones. So far, numerous saponins have been reported as components of Panax ginseng, also known as Korean ginseng. Herein, we summarize available information about 112 saponins related to P. ginseng; >80 of them are isolated from raw or processed ginseng, and the others are acid/base hydrolysates, semisynthetic saponins, or metabolites. PMID- 26869822 TI - Kinetic study for the optimization of ginsenoside Rg3 production by heat treatment of ginsenoside Rb1. AB - BACKGROUND: Ginsenoside Rg3 is a promising anticancer agent. It is usually produced by heat treatment of ginseng, in which ginsenoside Rb1 is the major ginsenoside. A kinetic study was conducted to optimize ginsenoside Rg3 production by the heat treatment of ginsenoside Rb1. METHODS: Ginsenoside Rb1 was heated using an isothermal machine at 80 degrees C and 100 degrees C and analyzed using HPLC. The kinetic parameters were calculated from the experimental results. The activation energy was estimated and used to simulate the process. The optimized parameters of ginsenoside Rg3 production are suggested based on the simulation. RESULTS: The rate constants were 0.013 h(-1) and 0.073 h(-1) for the degradation of ginsenosides Rb1 and Rg3 at 80 degrees C, respectively. The corresponding rate constants at 100 degrees C were 0.045 h(-1) and 0.155 h(-1). The estimated activation energies of degradation of ginsenosides Rb1 and Rg3 were 69.2 kJ/mol and 40.9 kJ/mol, respectively. The rate constants at different temperatures were evaluated using the estimated activation energies, and the kinetic profiles of ginsenosides Rb1 and Rg3 at each temperature were simulated based on the proposed kinetic model of consecutive reaction. The optimum strategies for producing ginsenoside Rg3 from ginsenoside Rb1 are suggested based on the simulation. With increased temperature, a high concentration of ginsenoside Rg3 is formed rapidly. However, the concentration decreases quickly after the reaching the maximal concentration value. CONCLUSION: The optimum temperature for producing ginsenoside Rg3 should be the highest temperature technically feasible below 180 degrees C, in consideration of the cooling time. The optimum reaction time for heat treatment is 30 min. PMID- 26869821 TI - Ginsenoside Rd and ischemic stroke; a short review of literatures. AB - Panax ginseng is a well-known economic medical plant that is widely used in Chinese traditional medicine. This species contains a unique class of natural products-ginsenosides. Recent clinical and experimental studies have presented numerous lines of evidence on the promising role of ginsenosides on different diseases including neurodegenerative diseases, cardiovascular diseases, and certain types of cancer. Nowadays, most of the attention has focused on ginsenoside Rd as a neuroprotective agent to attenuate ischemic stroke damages. Some of the evidence showed that ginsenoside Rd ameliorates ischemic stroke induced damages through the suppression of oxidative stress and inflammation. Ginsenoside Rd can prolong neural cells' survival through the upregulation of the endogenous antioxidant system, phosphoinositide-3-kinase/AKT and extracellular signal-regulated protein kinase 1/2 pathways, preservation of mitochondrial membrane potential, suppression of the nuclear factor-kappa B, transient receptor potential melastatin, acid sensing ion channels 1a, poly(ADP-ribose) polymerase 1, protein tyrosine kinase activation, as well as reduction of cytochrome c releasing and apoptosis-inducing factor. In the current work, we review the available reports on the promising role of ginsenoside Rd on ischemic stroke. We also discuss its chemistry, source, and the molecular mechanism underlying this effect. PMID- 26869823 TI - Ginsenoside Re inhibits pacemaker potentials via adenosine triphosphate-sensitive potassium channels and the cyclic guanosine monophosphate/nitric oxide-dependent pathway in cultured interstitial cells of Cajal from mouse small intestine. AB - BACKGROUND: Ginseng belongs to the genus Panax. Its main active ingredients are the ginsenosides. Interstitial cells of Cajal (ICCs) are the pacemaker cells of the gastrointestinal (GI) tract. To understand the effects of ginsenoside Re (GRe) on GI motility, the authors investigated its effects on the pacemaker activity of ICCs of the murine small intestine. METHODS: Interstitial cells of Cajal were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICCs. Changes in cyclic guanosine monophosphate (cGMP) content induced by GRe were investigated. RESULTS: Ginsenoside Re (20-40MUM) decreased the amplitude and frequency of ICC pacemaker activity in a concentration-dependent manner. This action was blocked by guanosine 5'-[beta-thio]diphosphate [a guanosine-5'-triphosphate (GTP)-binding protein inhibitor] and by glibenclamide [an adenosine triphosphate (ATP)-sensitive K(+) channel blocker]. To study the GRe-induced signaling pathway in ICCs, the effects of 1H-[1,2,4]oxadiazolo[4,3 a]quinoxalin-1-one (a guanylate cyclase inhibitor) and RP-8-CPT-cGMPS (a protein kinase G inhibitor) were examined. Both inhibitors blocked the inhibitory effect of GRe on ICC pacemaker activity. L-NG-nitroarginine methyl ester (100MUM), which is a nonselective nitric oxide synthase (NOS) inhibitor, blocked the effects of GRe on ICC pacemaker activity and GRe-stimulated cGMP production in ICCs. CONCLUSION: In cultured murine ICCs, GRe inhibits the pacemaker activity of ICCs via the ATP-sensitive potassium (K(+)) channel and the cGMP/NO-dependent pathway. Ginsenoside Re may be a basis for developing novel spasmolytic agents to prevent or alleviate GI motility dysfunction. PMID- 26869824 TI - Inhibitory mechanism of Korean Red Ginseng on GM-CSF expression in UVB-irradiated keratinocytes. AB - BACKGROUND: UV-irradiated keratinocytes secrete various proinflammatory cytokines. UV-induced skin damage is mediated by growth factors and proinflammatory cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF). In a previous study, we found that the saponin of Korean Red Ginseng (SKRG) decreased the expression of GM-CSF in UVB-irradiated SP-1 keratinocytes. In this study, we attempted to find the inhibitory mechanism of SKRG on UVB-induced GM-CSF expression in SP-1 keratinocytes. METHODS: We investigated the inhibitory mechanism of SKRG and ginsenosides from Panax ginseng on UVB-induced GM-CSF expression in SP-1 keratinocytes. RESULTS: Treatment with SKRG decreased the expression of GM-CSF mRNA and protein induced by irradiation of UVB in SP-1 keratinocytes. The phosphorylation of ERK was induced by UVB at 10 min, and decreased with SKRG treatment in SP-1 keratinocytes. In addition, treatment with SKRG inhibited the UVB-induced phosphorylation of epidermal growth factor receptor (EGFR), which is known to be an upstream signal of ERK. From these results, we found that the inhibition of GM-CSF expression by SKRG was derived from the decreased phosphorylation of EGFR. To identify the specific compound composing SKRG, we tested fifteen kinds of ginsenosides. Among these compounds, ginsenoside-Rh3 decreased the expression of GM-CSF protein and mRNA in SP-1 keratinocytes. CONCLUSION: Taken together, we found that treatment with SKRG decreased the phosphorylation of EGFR and ERK in UVB-irradiated SP-1 keratinocytes and subsequently inhibited the expression of GM-CSF. Furthermore, we identified ginsenoside-Rh3 as the active saponin in Korean Red Ginseng. PMID- 26869825 TI - Insulin sensitivity improvement of fermented Korean Red Ginseng (Panax ginseng) mediated by insulin resistance hallmarks in old-aged ob/ob mice. AB - BACKGROUND: The biological actions of various ginseng extracts have been studied for treating obesity and diabetes mellitus. However, few studies have evaluated the effects of fermented Korean Red Ginseng (Panax ginseng Meyer) on metabolic syndrome. The present study evaluated the antiobesity and antidiabetic effects of fermented red ginseng (FRG) on old-aged, obese, leptin-deficient (B6.V-Lepob, "ob/ob") mice. METHODS: The animals were divided into three groups and given water containing 0%, 0.5%, and 1.0% FRG for 16 wk. The effect of FRG on ob/ob mice was determined by measuring changes in body weight, levels of blood glucose, serum contents of triglycerides, total cholesterol and free fatty acids, messenger RNA (mRNA) expressions of key factors associated with insulin action, such as insulin receptor (IR), lipoprotein lipase (LPL), glucose transporter 1 and 4 (GLUT1 and GLUT4), peroxisome proliferators-activated receptor gamma (PPAR gamma), and phosphoenolpyruvate carboxykinase (PEPCK) in the liver and in muscle, and histology of the liver and pancreas. RESULTS: FRG-treated mice had decreased body weight and blood glucose levels compared with control ob/ob mice. However, anti-obesity effect of FRG was not evident rather than hypoglycemic effect in old aged ob/ob mice. The hyperlipidemia in control group was attenuated in FRG treated ob/ob mice. The mRNA expressions of IR, LPL, GLUT1, GLUT4, PPAR-gamma, and PEPCK in the liver and in muscle were increased in the FRG-treated groups compared with the control group. CONCLUSION: These results suggest that FRG may play a vital role in improving insulin sensitivity relative to reducing body weight in old-aged ob/ob mice. PMID- 26869826 TI - Accumulation characteristics and correlation analysis of five ginsenosides with different cultivation ages from different regions. AB - BACKGROUND: Ginseng (the roots of Panax ginseng Meyer) is a well-known traditional Oriental medicine and is now widely used as a health food. It contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. It has recently been reported that the qualitative and quantitative properties of ginsenosides found in ginseng may differ, depending on cultivation regions, ages, species, and so on. Therefore, it is necessary to study these variations with respect to cultivation ages and regions. METHODS: In this study, 3-6-yr-old roots of P. ginseng were collected from three different cultivation regions. The contents of five ginsenosides (Rb1, Rd, Rc, Re, and Rgl) were measured by rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The Kruskal-Wallis Rank sum test and multiple t test were used for comparative analysis of the data to evaluate the dynamic changes in the accumulation of these ginsenosides affected by cultivation regions and ages. RESULTS: The content and composition of ginsenosides varied significantly among specimens collected from different cultivation regions and having different cultivation ages. For all samples, the content of Rg1 and Re ginsenosides increases with age and this rate of increase is different for each sample. The contents of Rb1, Rc, and Rd varied with cultivation ages in samples from different cultivation regions; especially, Rb1 from a 6-yr-old root showed approximately twofold variation among the samples from three cultivation regions. Furthermore, the content of Rb1 highly correlated with that of Rd (r = 0.89 across all locations and ages). CONCLUSION: In our study, only the contents of ginsenosides Rg1 and Re were affected by the root age. Ginsenosides Rb1, Rc, and Rd varied widely with ages in samples from different cultivation regions. PMID- 26869827 TI - Photosynthesis rates, growth, and ginsenoside contents of 2-yr-old Panax ginseng grown at different light transmission rates in a greenhouse. AB - BACKGROUND: Ginseng is a semishade perennial plant cultivated in sloping, sun shaded areas in Korea. Recently, owing to air-environmental stress and various fungal diseases, greenhouse cultivation has been suggested as an alternative. However, the optimal light transmission rate (LTR) in the greenhouse has not been established. METHODS: The effect of LTR on photosynthesis rate, growth, and ginsenoside content of ginseng was examined by growing ginseng at the greenhouse under 6%, 9%, 13%, and 17% of LTR. RESULTS: The light-saturated net photosynthesis rate (A sat) and stomatal conductance (g s) of ginseng increased until the LTR reached 17% in the early stage of growth, whereas they dropped sharply owing to excessive leaf chlorosis at 17% LTR during the hottest summer period in August. Overall, 6-17% of LTR had no effect on the aerial part of plant length or diameter, whereas 17% and 13% of LRT induced the largest leaf area and the highest root weight, respectively. The total ginsenoside content of the ginseng leaves increased as the LTR increased, and the overall content of protopanaxatriol line ginsenosides was higher than that of protopanaxadiol line ginsenosides. The ginsenoside content of the ginseng roots also increased as the LTR increased, and the total ginsenoside content of ginseng grown at 17% LTR increased by 49.7% and 68.3% more than the ginseng grown at 6% LTR in August and final harvest, respectively. CONCLUSION: These results indicate that 13-17% of LTR should be recommended for greenhouse cultivation of ginseng. PMID- 26869829 TI - Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide induced inflammation in macrophage cells. AB - BACKGROUND: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. METHODS: Raw 264.7 cells were pretreated with GRo (up to 200MUM) for 1 h before treatment with 1 MUg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. RESULTS: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. CONCLUSION: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1. PMID- 26869828 TI - Inhibitory effects of total saponin from Korean Red Ginseng on [Ca(2+)]i mobilization through phosphorylation of cyclic adenosine monophosphate-dependent protein kinase catalytic subunit and inositol 1,4,5-trisphosphate receptor type I in human platelets. AB - BACKGROUND: Intracellular Ca(2+)([Ca(2+)]i) is a platelet aggregation-inducing molecule. Therefore, understanding the inhibitory mechanism of [Ca(2+)]i mobilization is very important to evaluate the antiplatelet effect of a substance. This study was carried out to understand the Ca(2+)-antagonistic effect of total saponin from Korean Red Ginseng (KRG-TS). METHODS: We investigated the Ca(2+)-antagonistic effect of KRG-TS on cyclic nucleotides associated phosphorylation of inositol 1,4,5-trisphosphate receptor type I (IP3RI) and cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) in thrombin (0.05 U/mL)-stimulated human platelet aggregation. RESULTS: The inhibition of [Ca(2+)]i mobilization by KRG-TS was increased by a PKA inhibitor (Rp-8-Br-cAMPS), which was more stronger than the inhibition by a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor (Rp-8-Br cGMPS). In addition, Rp-8-Br-cAMPS inhibited phosphorylation of PKA catalytic subunit (PKAc) (Thr(197)) by KRG-TS. The phosphorylation of IP3RI (Ser(1756)) by KRG-TS was very strongly inhibited by Rp-8-Br-cAMPS compared with that by Rp-8-Br cGMPS. These results suggest that the inhibitory effect of [Ca(2+)]i mobilization by KRG-TS is more strongly dependent on a cAMP/PKA pathway than a cGMP/PKG pathway. KRG-TS also inhibited the release of adenosine triphosphate and serotonin. In addition, only G-Rg3 of protopanaxadiol in KRG-TS inhibited thrombin-induced platelet aggregation. CONCLUSION: These results strongly indicate that KRG-TS is a potent beneficial compound that inhibits [Ca(2+)]i mobilization in thrombin-platelet interactions, which may result in the prevention of platelet aggregation-mediated thrombotic disease. PMID- 26869830 TI - Drying characteristics and quality of red ginseng using far-infrared rays. AB - BACKGROUND: The current typical drying methods for red ginseng are sun drying and hot-air drying. The purpose of this study was to investigate drying characteristics of red ginseng by using far-infrared drying. METHODS: The far infrared drying tests on red ginseng were conducted at two drying stages: (1) high temperature for 24 h drying and (2) low temperature drying until the final moisture content was 13 +/- 0.5% (wet basis). The high temperature drying stage included three drying chamber temperature conditions of 60 degrees C, 65 degrees C, and 70 degrees C. The low temperature drying stage was conducted at temperatures of 45 degrees C and 50 degrees C. Drying characteristics were analyzed based on factors such as drying rate, color changes, energy consumption, and saponin content. The results were compared with those of the hot-air and sun drying methods. RESULTS: The results revealed that increases in drying temperature caused a decrease in drying time and energy consumption for far infrared drying. The saponin content decreased under all drying conditions after drying, the highest value (11.34 mg/g) was observed at drying conditions of 60~50 degrees C. The sun drying condition showed the lowest color difference value when compared with far-infrared and hot-air drying. CONCLUSION: The far-infrared drying showed a faster drying rate, higher saponin content, lower color difference value, and a decrease in energy consumption than seen in hot-air drying. PMID- 26869831 TI - Protective effect of wild ginseng cambial meristematic cells on d-galactosamine induced hepatotoxicity in rats. AB - BACKGROUND: Panax ginseng has a wide range of biological activities including anti-inflammatory, antioxidant, and immunomodulatory functions. Wild ginseng cambial meristematic cells (CMCs) were obtained from P. ginseng cambium. This study examined the protective mechanism of wild ginseng CMCs against d galactosamine (GalN)-induced liver injury. GalN, a well-known hepatotoxicant, causes severe hepatocellular inflammatory damage and clinical features similar to those of human viral hepatitis in experimental animals. METHODS: Hepatotoxicity was induced in rats using GalN (700 mg/kg, i.p.). Wild ginseng CMCs was administered orally once a day for 2 wks, and then 2 h prior to and 6 h after GalN injection. RESULTS: Wild ginseng CMCs attenuated the increase in serum aminotransferase activity that occurs 24 h after GalN injection. Wild ginseng CMCs also attenuated the GalN-induced increase in serum tumor necrosis factor alpha, interleukin-6 level, and hepatic cyclooxygenase-2 protein and mRNA expression. Wild ginseng CMCs augmented the increase in serum interleukin -10 and hepatic heme oxygenase-1 protein and mRNA expression that was induced by GalN, inhibited the increase in the nuclear level of nuclear factor-kappa B, and enhanced the increase in NF-E2-related factor 2. CONCLUSION: Our findings suggest that wild ginseng CMCs protects liver against GalN-induced inflammation by suppressing proinflammatory mediators and enhancing production of anti inflammatory mediators. PMID- 26869832 TI - Characterization of Korean Red Ginseng (Panax ginseng Meyer): History, preparation method, and chemical composition. AB - It has been reported that Korean Red Ginseng has been manufactured for 1,123 y as described in the GoRyeoDoGyeong record. The Korean Red Ginseng manufactured by the traditional preparation method has its own chemical component characteristics. The ginsenoside content of the red ginseng is shown as Rg1: 3.3 mg/g, Re: 2.0 mg/g, Rb1: 5.8 mg/g, Rc:1.7 mg/g, Rb2: 2.3 mg/g, and Rd: 0.4 mg/g, respectively. It is known that Korean ginseng generally consists of the main root and the lateral or fine roots at a ratio of about 75:25. Therefore, the red ginseng extract is prepared by using this same ratio of the main root and lateral or fine roots and processed by the historical traditional medicine prescription. The red ginseng extract is prepared through a water extraction (90( degrees )C for 14-16 h) and concentration process (until its final concentration is 70-73 Brix at 50-60( degrees )C). The ginsenoside contents of the red ginseng extract are shown as Rg1: 1.3 mg/g, Re: 1.3 mg/g, Rb1: 6.4 mg/g, Rc:2.5 mg/g, Rb2: 2.3 mg/g, and Rd: 0.9 mg/g, respectively. Arginine-fructose-glucose (AFG) is a specific amino-sugar that can be produced by chemical reaction of the process when the fresh ginseng is converted to red ginseng. The content of AFG is 1.0 1.5% in red ginseng. Acidic polysaccharide, which has been known as an immune activator, is at levels of 4.5-7.5% in red ginseng. Therefore, we recommended that the chemical profiles of Korean Red Ginseng made through the defined traditional method should be well preserved and it has had its own chemical characteristics since its traditional development. PMID- 26869833 TI - Changes in the ginsenoside content during the fermentation process using microbial strains. AB - BACKGROUND: Red ginseng (RG) is processed from Panax ginseng via several methods including heat treatment, mild acid hydrolysis, and microbial conversion to transform the major ginsenosides into minor ginsenosides, which have greater pharmaceutical activities. During the fermentation process using microbial strains in a machine for making red ginseng, a change of composition occurs after heating. Therefore, we confirmed that fermentation had occurred using only microbial strains and evaluated the changes in the ginsenosides and their chemical composition. METHODS: To confirm the fermentation by microbial strains, the fermented red ginseng was made with microbial strains (w-FRG) or without microbial strains (n-FRG), and the fermentation process was performed to tertiary fermentation. The changes in the ginsenoside composition of the self-manufactured FRG using the machine were evaluated using HPLC, and the 20 ginsenosides were analyzed. Additionally, we investigated changes of the reducing sugar and polyphenol contents during fermentation process. RESULTS: In the fermentation process, ginsenosides Re, Rg1, and Rb1 decreased but ginsenosides Rh1, F2, Rg3, and Compound Y (C.Y) increased in primary FRG more than in the raw ginseng and RG. The content of phenolic compounds was high in FRG and the highest in the tertiary w-FRG. Moreover, the reducing sugar content was approximately three times higher in the tertiary w-FRG than in the other n-FRG. CONCLUSION: As the results indicate, we confirmed the changes in the ginsenoside content and the role of microbial strains in the fermentation process. PMID- 26869834 TI - A brief method for preparation of gintonin-enriched fraction from ginseng. AB - BACKGROUND: Ginseng has been used as a tonic for invigoration of the human body. In a previous report, we identified a novel candidate responsible for the tonic role of ginseng, designated gintonin. Gintonin induces [Ca(2+)]i transient in animal cells via lysophosphatidic acid receptor activation. Gintonin-mediated [Ca(2+)]i transient is linked to anti-Alzheimer's activity in transgenic Alzheimer's disease animal model. The previous method for gintonin preparation included multiple steps. The aim of this study is to develop a simple method of gintonin fraction with a high yield. METHODS: We developed a brief method to obtain gintonin using ethanol and water. We extracted ginseng with fermentation ethanol and fractionated the extract with water to obtain water-soluble and water insoluble fractions. The water-insoluble precipitate, rather than the water soluble supernatant, induced a large [Ca(2+)]i transient in primary astrocytes. We designated this fraction as gintonin-enriched fraction (GEF). RESULTS: The yield of GEF was approximately 6-fold higher than that obtained in the previous gintonin preparation method. The apparent molecular weight of GEF, determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was equivalent to that obtained in the previous gintonin preparation method. GEF induced [Ca(2+)]i transient in cortical astrocytes. The effective dose (ED50) was 0.3 +/- 0.09 MUg/mL. GEF used the same signal transduction pathway as gintonin during [Ca(2+)]i transient induction in mouse cortical astrocytes. CONCLUSION: Because GEF can be prepared through water precipitation of ginseng ethanol extract and is easily reproducible with high yield, it could be commercially utilized for the development of gintonin-derived functional health food and natural medicine. PMID- 26869835 TI - Leaf-specific pathogenesis-related 10 homolog, PgPR-10.3, shows in silico binding affinity with several biologically important molecules. AB - BACKGROUND: Pathogenesis-related 10 (PR-10) proteins are small, cytosolic proteins with a similar three-dimensional structure. Crystal structures for several PR-10 homologs have similar overall folding patterns, with an unusually large internal cavity that is a binding site for biologically important molecules. Although structural information on PR-10 proteins is substantial, understanding of their biological function remains limited. Here, we showed that one of the PgPR-10 homologs, PgPR-10.3, shares binding properties with flavonoids, kinetin, emodin, deoxycholic acid, and ginsenoside Re (1 of the steroid glycosides). METHODS: Gene expression patterns of PgPR-10.3 were analyzed by quantitative real-time PCR. The three-dimensional structure of PgPR-10 proteins was visualized by homology modeling, and docking to retrieve biologically active molecules was performed using AutoDock4 program. RESULTS: Transcript levels of PgPR-10.3 expressed in leaves, stems, and roots of 3-wk-old ginseng plantlets were on average 86-fold lower than those of PgPR-10.2. In mature 2-yr-old ginseng plants, the mRNA of PgPR-10.3 is restricted to leaves. Ginsenoside Re production is especially prominent in leaves of Panax ginseng Meyer, and the binding property of PgPR-10.3 with ginsenoside Re suggests that this protein has an important role in the control of secondary metabolism. CONCLUSION: Although ginseng PR-10.3 gene is expressed in all organs of 3-wk-old plantlets, its expression is restricted to leaves in mature 2-yr-old ginseng plants. The putative binding property of PgPR-10.3 with Re is intriguing. Further verification of binding affinity with other biologically important molecules in the large hydrophobic cavity of PgPR-10.3 may provide an insight into the biological features of PR-10 proteins. PMID- 26869836 TI - Effects of Korean Red Ginseng marc with aluminum sulfate against pathogen populations in poultry litters. AB - BACKGROUND: The aim of this study was to evaluate the effects of Korean Red Ginseng marc with aluminum sulfate as litter amendments on ammonia, soluble reactive phosphorus, and pathogen populations in poultry litters. METHODS: Increasing levels of Korean Red Ginseng marc with aluminum sulfate were applied onto the surface of rice hull as a top-dress application; untreated rice hulls served as controls. RESULTS: Treatment with Korean Red Ginseng marc with aluminum sulfate or aluminum sulfate alone resulted in lower litter pH (p < 0.05), as compared with that of the controls. There were some differences (p < 0.05) between treatments with Korean Red Ginseng marc with aluminum sulfate or aluminum sulfate alone and controls at 2-4 wk (not at 1 wk). Ammonia levels reduced on an average by 29%, 30%, and 32% for 10 g, 20 g Korean Red Ginseng marc with aluminum sulfate, and aluminum sulfate alone, respectively, as compared with controls at 4 wk. During the experiment, Korean Red Ginseng marc with aluminum sulfate or aluminum sulfate treatment had an effect (p < 0.05) on soluble reactive phosphorus content, as compared with the controls (not at 4 wk). A decrease in Salmonella enterica and Escherichia coli was observed (p < 0.05) in litter amended with both Korean Red Ginseng marc with aluminum sulfate and aluminum sulfate alone, as compared with the control, except at 1-3 wk for Salmonella enterica and 1 wk and 4 wk for Escherichia coli, respectively. CONCLUSION: The results showed that using Korean Red Ginseng marc with aluminum sulfate (blends), which act as acidifying agents by reducing the pH of the litter, was equally effective as aluminum sulfate in reducing the environmental impact. PMID- 26869837 TI - Emotional processing needs further study in major psychiatric diseases. AB - Emotions are largely affected in many psychiatric diseases. A better understanding of the neural networks involved in emotion processing is an important way to be able to improve dysfunctions in emotion recognition, as well as expression, associated with major psychiatric disorders. PMID- 26869838 TI - Affective preclinical modeling of psychiatric disorders: taking imbalanced primal emotional feelings of animals seriously in our search for novel antidepressants. AB - Preclinical animal models of psychiatric disorders are of critical importance for advances in development of new psychiatric medicine. Regrettably, behavior-only models have yielded no novel targeted treatments during the past half-century of vigorous deployment. This may reflect the general neglect of experiential aspects of animal emotions, since affective mental states of animals supposedly cannot be empirically monitored. This supposition is wrong-to the extent that the rewarding and punishing aspects of emotion circuit arousals reflect positive and negative affective states. During the past decade, the use of such affective neuroscience based animal modeling has yielded three novel antidepressants (i) via the alleviation of psychic pain with low doses of buprenorphine; (ii) via the amplification of enthusiasm by direct stimulation of the medial forebrain bundle); and (iii) via the facilitation of the capacity for social joy with play facilitators such as rapastinel (GLYX13). All have progressed to successful human testing. For optimal progress, it may be useful for preclinical investigators to focus on the evolved affective foundations of psychiatrically relevant brain emotional disorders for optimal animal modeling. PMID- 26869839 TI - Affiliative and prosocial motives and emotions in mental health. AB - This paper argues that studies of mental health and wellbeing can be contextualized within an evolutionary approach that highlights the coregulating processes of emotions and motives. In particular, it suggests that, although many mental health symptoms are commonly linked to threat processing, attention also needs to be directed to the major regulators of threat processing, ie, prosocial and affiliative interactions with self and others. Given that human sociality has been a central driver for a whole range of human adaptations, a better understanding of the effects of prosocial interactions on health is required, and should be integrated into psychiatric formulations and interventions. Insight into the coregulating processes of motives and emotions, especially prosocial ones, offers improved ways of understanding mental health difficulties and their prevention and relief. PMID- 26869840 TI - Emotor control: computations underlying bodily resource allocation, emotions, and confidence. AB - Emotional processes are central to behavior, yet their deeply subjective nature has been a challenge for neuroscientific study as well as for psychiatric diagnosis. Here we explore the relationships between subjective feelings and their underlying brain circuits from a computational perspective. We apply recent insights from systems neuroscience-approaching subjective behavior as the result of mental computations instantiated in the brain-to the study of emotions. We develop the hypothesis that emotions are the product of neural computations whose motor role is to reallocate bodily resources mostly gated by smooth muscles. This "emotor" control system is analagous to the more familiar motor control computations that coordinate skeletal muscle movements. To illustrate this framework, we review recent research on "confidence." Although familiar as a feeling, confidence is also an objective statistical quantity: an estimate of the probability that a hypothesis is correct. This model-based approach helped reveal the neural basis of decision confidence in mammals and provides a bridge to the subjective feeling of confidence in humans. These results have important implications for psychiatry, since disorders of confidence computations appear to contribute to a number of psychopathologies. More broadly, this computational approach to emotions resonates with the emerging view that psychiatric nosology may be best parameterized in terms of disorders of the cognitive computations underlying complex behavior. PMID- 26869841 TI - What develops during emotional development? A component process approach to identifying sources of psychopathology risk in adolescence. AB - Adolescence is a phase of the lifespan associated with widespread changes in emotional behavior thought to reflect both changing environments and stressors, and psychological and neurobiological development. However, emotions themselves are complex phenomena that are composed of multiple subprocesses. In this paper, we argue that examining emotional development from a process-level perspective facilitates important insights into the mechanisms that underlie adolescents' shifting emotions and intensified risk for psychopathology. Contrasting the developmental progressions for the antecedents to emotion, physiological reactivity to emotion, emotional regulation capacity, and motivation to experience particular affective states reveals complex trajectories that intersect in a unique way during adolescence. We consider the implications of these intersecting trajectories for negative outcomes such as psychopathology, as well as positive outcomes for adolescent social bonds. PMID- 26869842 TI - The rise of moral emotions in neuropsychiatry. AB - Clinical psychopathology has largely ignored the developments in the field of social neuroscience. The so-called moral emotions are a group of affective experiences thought to promote cooperation, group cohesion, and reorganization. In this review, we: (i) briefly describe a provisional taxonomy of a limited set of moral emotions and their neural underpinnings; and (ii) discuss how disgust, guilt, anger/indignation, and shame/embarrassment can be conceptualized as key affective experiences in different neuropsychiatric disorders. Based on a concise review of the literature linking moral emotions, psychopathology, and neuropsychiatry, we have devised a simple and preliminary scheme where we conjecture how specific moral emotions can be implicated in some categories of DSM-5 diagnoses, potentially helping to bridge psychopathology and neurobiologically plausible variables, in line with the Research Domain Criteria initiative. We hope this stimulates new empirical work exploring how moral emotional changes and their underlying neurobiology can help elucidating the neural underpinnings of mental disorders. PMID- 26869844 TI - Emotional responses to interpersonal rejection. AB - A great deal of human emotion arises in response to real, anticipated, remembered, or imagined rejection by other people. Because acceptance by other people improved evolutionary fitness, human beings developed biopsychological mechanisms to apprise them of threats to acceptance and belonging, along with emotional systems to deal with threats to acceptance. This article examines seven emotions that often arise when people perceive that their relational value to other people is low or in potential jeopardy, including hurt feelings, jealousy, loneliness, shame, guilt, social anxiety, and embarrassment. Other emotions, such as sadness and anger, may occur during rejection episodes, but are reactions to features of the situation other than low relational value. The article discusses the evolutionary functions of rejection-related emotions, neuroscience evidence regarding the brain regions that mediate reactions to rejection, and behavioral research from social, developmental, and clinical psychology regarding psychological and behavioral concomitants of interpersonal rejection. PMID- 26869845 TI - Compound facial expressions of emotion: from basic research to clinical applications. AB - Emotions are sometimes revealed through facial expressions. When these natural facial articulations involve the contraction of the same muscle groups in people of distinct cultural upbringings, this is taken as evidence of a biological origin of these emotions. While past research had identified facial expressions associated with a single internally felt category (eg, the facial expression of happiness when we feel joyful), we have recently studied facial expressions observed when people experience compound emotions (eg, the facial expression of happy surprise when we feel joyful in a surprised way, as, for example, at a surprise birthday party). Our research has identified 17 compound expressions consistently produced across cultures, suggesting that the number of facial expressions of emotion of biological origin is much larger than previously believed. The present paper provides an overview of these findings and shows evidence supporting the view that spontaneous expressions are produced using the same facial articulations previously identified in laboratory experiments. We also discuss the implications of our results in the study of psychopathologies, and consider several open research questions. PMID- 26869846 TI - Measuring facial expression of emotion. AB - Research into emotions has increased in recent decades, especially on the subject of recognition of emotions. However, studies of the facial expressions of emotion were compromised by technical problems with visible video analysis and electromyography in experimental settings. These have only recently been overcome. There have been new developments in the field of automated computerized facial recognition; allowing real-time identification of facial expression in social environments. This review addresses three approaches to measuring facial expression of emotion and describes their specific contributions to understanding emotion in the healthy population and in persons with mental illness. Despite recent progress, studies on human emotions have been hindered by the lack of consensus on an emotion theory suited to examining the dynamic aspects of emotion and its expression. Studying expression of emotion in patients with mental health conditions for diagnostic and therapeutic purposes will profit from theoretical and methodological progress. PMID- 26869843 TI - Emotional and cognitive dysregulation in schizophrenia and depression: understanding common and distinct behavioral and neural mechanisms. AB - Emerging behavioral and neuroimaging studies in schizophrenia (SCZ) and major depressive disorder (MD) are mapping mechanisms of co-occurring and distinct affective disturbances across these disorders. This constitutes a critical goal towards developing rationally guided therapies for upstream neural pathways that contribute to comorbid symptoms across disorders. We highlight the current state of the art in our understanding of emotional dysregulation in SCZ versus MD by focusing on broad domains of behavioral function that can map onto underlying neural systems, namely deficits in hedonics, anticipatory behaviors, computations underlying value and effort, and effortful goal-directed behaviors needed to pursue rewarding outcomes. We highlight unique disturbances in each disorder that may involve dissociable neural systems, but also possible interactions between affect and cognition in MD versus SCZ. Finally, we review computational and translational approaches that offer mechanistic insight into how cellular-level disruptions can lead to complex affective disturbances, informing development of therapies across MD and SCZ. PMID- 26869848 TI - The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment. AB - Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients. PMID- 26869849 TI - QTL mapping for bacterial wilt resistance in peanut (Arachis hypogaea L.). AB - Bacterial wilt (BW) caused by Ralstonia solanacearum is a serious, global, disease of peanut (Arachis hypogaea L.), but it is especially destructive in China. Identification of DNA markers linked to the resistance to this disease will help peanut breeders efficiently develop resistant cultivars through molecular breeding. A F2 population, from a cross between disease-resistant and disease-susceptible cultivars, was used to detect quantitative trait loci (QTL) associated with the resistance to this disease in the cultivated peanut. Genome wide SNPs were identified from restriction-site-associated DNA sequencing tags using next-generation DNA sequencing technology. SNPs linked to disease resistance were determined in two bulks of 30 resistant and 30 susceptible plants along with two parental plants using bulk segregant analysis. Polymorphic SSR and SNP markers were utilized for construction of a linkage map and for performing the QTL analysis, and a moderately dense linkage map was constructed in the F2 population. Two QTL (qBW-1 and qBW-2) detected for resistance to BW disease were located in the linkage groups LG1 and LG10 and account for 21 and 12 % of the bacterial wilt phenotypic variance. To confirm these QTL, the F8 RIL population with 223 plants was utilized for genotyping and phenotyping plants by year and location as compared to the F2 population. The QTL qBW-1 was consistent in the location of LG1 in the F8 population though the QTL qBW-2 could not be clarified due to fewer markers used and mapped in LG10. The QTL qBW-1, including four linked SNP markers and one SSR marker within 14.4-cM interval in the F8, was closely related to a disease resistance gene homolog and was considered as a candidate gene for resistance to BW. QTL identified in this study would be useful to conduct marker-assisted selection and may permit cloning of resistance genes. Our study shows that bulk segregant analysis of genome-wide SNPs is a useful approach to expedite the identification of genetic markers linked to disease resistance traits in the allotetraploidy species peanut. PMID- 26869850 TI - Systematic analysis of the use of amphipathic polymers for studies of outer membrane proteins using mass spectrometry. AB - Membrane proteins (MPs) are essential for numerous important biological processes. Recently, mass spectrometry (MS), coupled with an array of related techniques, has been used to probe the structural properties of MPs and their complexes. Typically, detergent micelles have been employed for delivering MPs into the gas-phase, but these complexes have intrinsic properties that can limit the utility of structural studies of MPs using MS methods. Amphipols (APols) have advantages over detergent micelles and have been shown to be capable of delivering native MPs into the gas-phase. Comparing six different APols which vary in mass and charge, and the detergent n-dodecyl-beta-d-maltopyranoside, we aimed to determine which APols are most efficient for delivery of native outer membrane proteins (OMPs) into the gas-phase. We show that maintaining the solution-phase folding and global structures of three different OMPs (PagP, OmpT and tOmpA) are independent of the APol used, but differences in OMP activity can result from the different APol:OMP complexes. ESI-IMS-MS analysis of OMP:APol complexes shows that the A8-35 APol is most proficient at liberating all three OMPs into the gas-phase, without altering their gas-phase conformations. PMID- 26869847 TI - Oxytocin in the socioemotional brain: implications for psychiatric disorders. AB - The neuropeptide oxytocin (OXT), highly conserved during evolution, is an important modulator of social and emotional processes across many species. During the last decade, a large body of literature has revealed its effects on different aspects of social behavior, including social stress and anxiety, social memory, affiliation and bonding, emotion recognition, mentalizing, empathy, and interpersonal trust. In addition, as impairments in these social domains can be observed in a number of neuropsychiatric disorders, such as autism, social anxiety disorder, depression, schizophrenia, and borderline personality disorder, the role of OXT in mental disorders and their treatment has been intensively studied. The present paper gives a short overview of these lines of research and shows how OXT has become a promising target for novel treatment approaches for mental disorders characterized by social impairments. PMID- 26869851 TI - Protein profiling of mefloquine resistant Plasmodium falciparum using mass spectrometry-based proteomics. AB - Malaria is a mosquito borne infectious disease caused by protozoa of genus Plasmodium. There are five species of Plasmodium that are found to infect humans. Plasmodium falciparum can cause severe malaria leading to higher morbidity and mortality of malaria than the other four species. Antimalarial resistance is the major obstacle to control malaria. Mefloquine was used in combination with Artesunate for uncomplicated P. falciparum in South East Asia and it has developed and established mefloquine resistance in this region. Here, gel enhanced liquid chromatography/tandem mass spectrometry (GeLC-MS/MS)-based proteomics and label-free quantification were used to explore the protein profiles of mefloquine-sensitive and -induced resistant P. falciparum. A Thai P. falciparum isolate (S066) was used as a model in this research. Our data revealed for the first time that 69 proteins exhibited at least 2-fold differences in their expression levels between the two parasite lines. Of these, 36 were up regulated and 33 were down-regulated in the mefloquine-resistant line compared with the mefloquine-sensitive line. These findings are consistent with those of past studies, where the multidrug resistance protein Pgh1 showed an up-regulation pattern consistent with that expected from its average 3-copy pfmdr1 gene number. Pgh1 and eight other up-regulated proteins (i.e., histo-aspartyl protease protein, exportin 1, eukaryotic translation initiation factor 3 subunit 8, peptidyl-prolyl cis-trans isomerase, serine rich protein homologue, exported protein 1, ATP synthase beta chain and phospholipid scramblase 1) were further validated for their expression levels using reverse transcriptase quantitative real-time PCR. The data support the up-regulation status in the mefloquine resistant parasite line of all the candidate genes referred to above. Therefore, GeLC-MS/MS-based proteomics combined with label-free quantification is a reliable approach for exploring mefloquine resistance biomarkers in P. falciparum. Identification of these proteins leads to better understanding of mefloquine resistant mechanisms in malaria parasites. PMID- 26869853 TI - Evaluation of dimethyl sulfoxide (DMSO) as a mobile phase additive during top 3 label-free quantitative proteomics. AB - Dimethyl sulfoxide (DMSO) has been advocated as a beneficial additive to electrospray solvents for peptide analysis due to the improved ionisation efficiency conferred. Previous reports have shown that the resultant improvements in peptide ion signal intensities are non-uniform. As a result, it was hypothesised that inclusion of DMSO in electrospray solvents could be detrimental to the outcome of intensity-based label-free absolute quantification approaches, specifically the top 3 method. The effect of DMSO as a mobile phase additive in top 3 label-free quantification was therefore evaluated. We show that inclusion of DMSO enhances data quality, improving the precision and number of proteins quantified, with no significant change to the quantification values observed in its absence. PMID- 26869852 TI - Evaluating the use of HILIC in large-scale, multi dimensional proteomics: Horses for courses? AB - Despite many recent advances in instrumentation, the sheer complexity of biological samples remains a major challenge in large-scale proteomics experiments, reflecting both the large number of protein isoforms and the wide dynamic range of their expression levels. However, while the dynamic range of expression levels for different components of the proteome is estimated to be ~107-8, the equivalent dynamic range of LC-MS is currently limited to ~106. Sample pre-fractionation has therefore become routinely used in large-scale proteomics to reduce sample complexity during MS analysis and thus alleviate the problem of ion suppression and undersampling. There is currently a wide range of chromatographic techniques that can be applied as a first dimension separation. Here, we systematically evaluated the use of hydrophilic interaction liquid chromatography (HILIC), in comparison with hSAX, as a first dimension for peptide fractionation in a bottom-up proteomics workflow. The data indicate that in addition to its role as a useful pre-enrichment method for PTM analysis, HILIC can provide a robust, orthogonal and high-resolution method for increasing the depth of proteome coverage in large-scale proteomics experiments. The data also indicate that the choice of using either HILIC, hSAX, or other methods, is best made taking into account the specific types of biological analyses being performed. PMID- 26869856 TI - Mitchel Seruya, MD. PMID- 26869854 TI - Characterisation of bioenergetic pathways and related regulators by multiple assays in human tumour cells. AB - BACKGROUND: Alterations in cellular metabolism are considered as hallmarks of cancers, however, to recognize these alterations and understand their mechanisms appropriate techniques are required. Our hypothesis was to determine whether dominant bioenergetic mechanism may be estimated by comparing the substrate utilisation with different methods to detect the labelled carbon incorporation and their application in tumour cells. METHODS: To define the bioenergetic pathways different metabolic tests were applied: (a) measuring CO2 production from [1-(14)C]-glucose and [1-(14)C]-acetate; (b) studying the effect of glucose and acetate on adenylate energy charge; (c) analysing glycolytic and TCA cycle metabolites and the number of incorporated (13)C atoms after [U-(13)C]-glucose/[2 (13)C]-acetate labelling. Based on [1-(14)C]-substrate oxidation two selected cell lines out of seven were analysed in details, in which the highest difference was detected at their substrate utilization. To elucidate the relevance of metabolic characterisation the expression of certain regulatory factors, bioenergetic enzymes, mammalian target of rapamycin (mTOR) complexes (C1/C2) and related targets as important elements at the crossroad of cellular signalling network were also investigated. RESULTS: Both [U-(13)C]-glucose and [1-(14)C] substrate labelling indicated high glycolytic capacity of tumour cells. However, the ratio of certain (13)C-labelled metabolites showed detailed metabolic differences in the two selected cell lines in further characterisation. The detected differences of GAPDH, beta-F1-ATP-ase expression and adenylate energy charge in HT-1080 and ZR-75.1 tumour cells also confirmed the altered metabolism. Moreover, the highly limited labelling of citrate by [2-(13)C]-acetate representing a novel functional test in malignant cells-confirmed the defect of TCA cycle of HT-1080 in contrast to ZR-75.1 cells. Noteworthy, the impaired TCA cycle in HT-1080 cells were associated with high mTORC1 activity, negligible protein level and activity of mTORC2, high expression of interleukin-1beta, interleukin-6 and heme oxygenase-1 which may contribute to the compensatory mechanism of TCA deficiency. CONCLUSIONS: The applied methods of energy substrate utilisation and other measurements represent simple assay system using (13)C acetate and glucose to recognize dominant bioenergetic pathways in tumour cells. These may offer a possibility to characterise metabolic subtypes of human tumours and provide guidelines to find biomarkers for prediction and development of new metabolism related targets in personalized therapy. PMID- 26869855 TI - Feasibility of Undertaking Off-Site Infant Eye-Tracking Assessments of Neuro Cognitive Functioning in Early-Intervention Centres. AB - Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to persuade low-SES parents to come to a university setting. One solution is to recruit infants through early intervention children's centres (CCs). These are often located in areas of high relative deprivation to support young children. Given the increasing portability of eye-tracking equipment, assessment of large clusters of infants could be undertaken in centres by suitably trained early intervention staff. Here, we report on a study involving 174 infants and their parents, carried out in partnership with CCs, exploring the feasibility of this approach. We report the processes of setting up the project and participant recruitment. We report the diversity of sample obtained on the engagement of CC staff in training and the process of assessment itself. We report the quality of the data obtained, and the levels of engagement of parents and infants. We conclude that this approach has great potential for recruiting large and diverse samples worldwide, provides sufficiently reliable data and is engaging to staff, parents and infants. PMID- 26869857 TI - Pediatric Upper Limb Spasticity. PMID- 26869858 TI - Grading and Quantification of Upper Extremity Function in Children with Spasticity. AB - The World Health Organization's International Classification of Functioning, Disability and Health (ICF) provides an ideal framework within which to conceptualize grading and quantification of upper extremity function for children with spasticity. In this article the authors provide an overview of assessments and classification tools used to (1) understand upper extremity function associated with spasticity and the factors that contribute to dysfunction, (2) guide the selection of appropriate interventions, (3) identify specific muscles to target using surgical interventions and botulinum toxin-A injections, and (4) measure the outcomes of upper extremity interventions. Assessments of upper extremity function are briefly described and categorized as to whether they (1) measure children's best ability or actual performance in daily life, (2) are clinician administered or are a child/proxy report, (3) assist in planning intervention and/or measuring outcomes, and (4) evaluate unimanual or bimanual ability. In addition, measures of spasticity and hypertonicity, and classifications of static and dynamic upper extremity postures are summarized. PMID- 26869860 TI - Botulinum Toxin in the Treatment of Pediatric Upper Limb Spasticity. AB - Botulinum neurotoxin (BoNT) is one of the mainstays in the treatment of pediatric spasticity and dystonia. When considering initiation of BoNT treatment for spasticity, treatment goals and responses to prior conservative measures such as passive range of motion exercises, splinting, and other medication trials should be reviewed. As a general rule, children should be engaged in therapy services around the time of the injections and have a robust home program in place. When managing spasticity in children with BoNT injections, the practitioner should be well versed in functional anatomy with specialized training in injection techniques. Localization techniques in addition to anatomical landmarks are recommended for improved efficacy and include limited electromyography, electrical stimulation, and/or ultrasound guidance. A follow-up visit for the purpose of reassessment during the peak effect of the drug is advised. It is known that BoNT is effective at reducing spasticity and improving range of motion, but it remains to be determined to what degree this translates into improved function, activity, and participation. PMID- 26869859 TI - Review of Therapeutic Interventions for the Upper Limb Classified by Manual Ability in Children with Cerebral Palsy. AB - The aim of this literature review was to assemble an inventory of intervention strategies utilized for children diagnosed with cerebral palsy (CP) based on the Manual Ability Classification System (MACS). The purpose of the inventory is to guide physicians and therapists in intervention selection aimed at improving upper limb function in children with CP. The following databases were searched: CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane Database of Systematic Reviews, ERIC (Educational Research Information Center), Google Scholar, OTSeeker (Occupational Therapy Systematic Evaluation of Evidence), OVID (Ovid Technologies, Inc.), and PubMed. Inclusion criteria were whether the study (1) identified MACS levels of participants, and (2) addressed the effectiveness of intervention on upper limb function. Overall, 74 articles met the inclusion criteria. The summarized data identified 10 categories of intervention. The majority of participants across studies were MACS level II. The most frequently cited interventions were constraint-induced movement therapy (CIMT), bimanual training, and virtual reality and computer-based training. Multiple interventions demonstrated effectiveness for upper limb improvement at each MACS level. However, there is a need for additional research for interventions appropriate for MACS levels IV and V. To fully develop an intervention inventory based on manual ability, future studies need to report MACS levels of participants, particularly for splinting and therapy interventions used in combination with surgery. PMID- 26869861 TI - Surgical Treatment of Pediatric Upper Limb Spasticity: The Wrist and Hand. AB - The wrist and hand are essential in the placement of the upper extremity in a functional position for grasp, pinch, and release activities. This depends on the delicate balance between the extrinsic and intrinsic muscles of the wrist and hand. Spasticity alters this equilibrium, limiting the interaction of the upper limb with the environment. Classically, pediatric patients with upper limb spasticity present with a flexed wrist, thumb-in-palm, and flexed finger posture. These contractures are typically secondary to spasticity of the extrinsic flexor muscles of the wrist and hand and intrinsic muscles of the thumb and digits. Tendon release, lengthening, or transfer procedures may help correct the resultant abnormal postures. A total wrist arthrodesis with or without proximal row carpectomy may help address the severely flexed wrist deformity. With proper diagnosis, a well-executed surgical plan, and a consistent hand rehabilitation regimen, successful surgical outcomes can be achieved. PMID- 26869862 TI - Spastic Paralysis of the Elbow and Forearm. AB - As the physiologic recovery period concludes, the patient is evaluated for surgical procedures that may rebalance muscle function and correct deformity. Upper extremity function is the product of complex and highly sophisticated mechanisms working in unison, and a careful, systematic preoperative evaluation is critical. A good function of the hand cannot be achieved without adequate position of the shoulder, elbow, forearm, and wrist. The goals of surgery must be practical and clearly understood by the patient and the family. PMID- 26869863 TI - Surgical Treatment of Pediatric Upper Limb Spasticity: The Shoulder. AB - The shoulder joint is essential for placing the hand in a functional position for reach and overhead activities. This depends on the delicate balance between abductor/adductor and internal/external rotator muscles. Spasticity alters this equilibrium, limiting the interaction of the upper limb with the environment. Classically, pediatric patients with upper limb spasticity present with an adduction and internal rotation contracture of the shoulder. These contractures are typically secondary to spasticity of the pectoralis major and subscapularis muscles and sometimes attributed to the latissimus dorsi muscle. Fractional lengthening, Z-step lengthening, or tendon release of the contributing muscle groups may help correct the adduction and internal rotation contractures. With proper diagnosis, a well-executed surgical plan, and a consistent hand rehabilitation regimen, successful surgical outcomes can be achieved. PMID- 26869864 TI - Transmitting Chinese Medicine: Changing Perceptions of Body, Pathology, and Treatment in Late Imperial China. AB - Historians of Chinese medicine acknowledge the plurality of Chinese medicine along both synchronic and diachronic dimensions. Yet, there remains a tendency to think of tradition as being defined by some unchanging features. The Chinese medical body is a case in point. This is assumed to have been formalised by the late Han dynasty around a system of internal organs, conduits, collaterals, and associated body structures. Although criticism was voiced from time to time, this body and the micro/macrocosmic cosmological resonances that underpin it are seen to persist until the present day. I challenge this view by attending to attempts by physicians in China and Japan in the period from the mid 16th to the late 18th century to reimagine this body. Working within the domain of cold damage therapeutics and combining philological scholarship, empirical observations, and new hermeneutic strategies these physicians worked their way towards a new territorial understanding of the body and of medicine as warfare that required an intimate familiarity with the body's topography. In late imperial China this new view of the body and medicine was gradually re-absorbed into the mainstream. In Japan, however, it led to a break with this orthodoxy that in the Republican era became influential in China once more. I argue that attending further to the innovations of this period from a transnational perspective - commonly portrayed as one of decline - may help to go beyond the modern insistence to frame East Asian medicines as traditional. PMID- 26869867 TI - Development and characterization of a new human hepatic cell line. AB - The increasing demand and hampered use of primary human hepatocytes for research purposes have urged scientists to search for alternative cell sources, such as immortalized hepatic cell lines. The aim of this study was to develop a human hepatic cell line using the combined overexpression of TERT and the cell cycle regulators cyclin D1 and mutant isoform CDK4R24C. Following transduction of adult human primary hepatocytes with the selected immortalization genes, cell growth was triggered and a cell line was established. When cultured under appropriate conditions, the cell line expressed several hepatocytic markers and liver enriched transcription factors at the transcriptional and/or translational level, secreted liver-specific proteins and showed glycogen deposition. These results suggest that the immortalization strategy applied to primary human hepatocytes could generate a novel hepatic cell line that seems to retain some key hepatic characteristics. PMID- 26869865 TI - A systematic review of the cardiotoxicity of methadone. AB - Methadone is one of the most popular synthetic opioids in the world with some favorable properties making it useful both in the treatment of moderate to severe pain and for opioid addiction. Increased use of methadone has resulted in an increased prevalence of its toxicity, one aspect of which is cardiotoxicity. In this paper, we review the effects of methadone on the heart as well as cardiac concerns in some special situations such as pregnancy and childhood. METHODS: We searched for the terms methadone, toxicity, poisoning, cardiotoxicity, heart, dysrhythmia, arrhythmia, QT interval prolongation, torsade de pointes, and Electrocardiogram (ECG) in bibliographical databases including TUMS digital library, PubMed, Scopus, and Google Scholar. This review includes relevant articles published between 2000 and 2013. The main cardiac effects of methadone include prolongation of QT interval and torsade de pointes. Other effects include changes in QT dispersion, pathological U waves, Taku-Tsubo syndrome (stress cardiomyopathy), Brugada-like syndrome, and coronary artery diseases. The aim of this paper is to inform physicians and health care staff about these adverse effects. Effectiveness of methadone in the treatment of pain and addiction should be weighed against these adverse effects and physicians should consider the ways to lessen such undesirable effects. This article presents some recommendations to prevent heart toxicity in methadone users. PMID- 26869866 TI - Plants with potential use on obesity and its complications. AB - Obesity is the most prevalent nutritional disease and a growing public health problem worldwide. This disease is a causal component of the metabolic syndrome related with abnormalities, including hyperglycemia, dyslipidemia, hypertension, inflammation, among others. There are anti-obesity drugs, affecting the fundamental processes of the weight regulation; however they have shown serious side effects, which outweigh their beneficial effects. Most recent studies on the treatment of obesity and its complications have focused on the potential role of different plants preparation that can exert a positive effect on the mechanisms involved in this pathology. For instance, anti-obesity effects of green tea and its isolated active principles have been reported in both in vitro (cell cultures) and in vivo (animal models) that possess healthy effects, decreasing adipose tissue through reduction of adipocytes differentiation and proliferation. A positive effect in lipid profile, and lipid and carbohydrates metabolisms were demonstrated as well. In addition, anti-inflammatory and antioxidant activities were studied. However, the consumption of green tea and its products is not that common in Western countries, where other plants with similar bioactivity predominate; nevertheless, the effect extension has not been analyzed in depth, despite of their potential as alternative treatment for obesity. In this review the anti-obesity potential and reported mechanisms of action of diverse plants such as: Camellia sinensis, Hibiscus sabdariffa, Hypericum perforatum, Persea americana, Phaseolus vulgaris, Capsicum annuum, Rosmarinus officinalis, Ilex paraguariensis, Citrus paradisi, Citrus limon, Punica granatum, Aloe vera, Taraxacum officinale and Arachis hypogaea is summarized. We consider the potential of these plants as natural alternative treatments of some metabolic alterations associated with obesity. PMID- 26869868 TI - Synergistic effects of nitric oxide and exercise on revascularisation in the infarcted ventricle in a murine model of myocardial infarction. AB - It has been shown that density of microvessels decreases in the left ventricular after myocardial infarction (MI). The change of angiogenic and angiostatic factors as the main factors in revascularisation after exercise training in area at risk is not determined yet in MI. Therefore, the aim of the present study was the effect of exercise training and L-arginine supplementation on area at risk angiogenesis in myocardial infarction rat. Four weeks after surgery (Left Anterior Descending Coronary artery Ligation), myocardial infarction rats were divided into 4 groups: Sedentary rats (Sed-MI); L-arginine supplementation (La MI); Exercise training (Ex-MI) and Exercise + L-arginine (Ex+La). Exercise training (ET) lasted for 10 weeks at 17 m/min for 10-50 min day(-1). Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. After ET and L arginine supplementation, ventricular function was evaluated and angiogenic and angiostatic indices were measured at ~1 mm from the edge of scar tissue (area at risk). Statistical analysis revealed that gene expression of VEGF as an angiogenic factor, angiostatin as an angiostatic factor and caspase-3 at area at risk decrease significantly in response to exercise training compared to the sedentary group. The capillary and arteriolar density in the Ex groups were significantly higher than those of the Sed groups. Compared to the Ex-MI group, the Ex+La group showed a markedly increase in capillary to fiber ratio. No significant differences were found in infarct size among the four groups, but cardiac function increased in response to exercise. Exercise training increases revascularization at area at risk by reduction of angiostatin. L-arginine supplementation causes additional effects on exercise-induced angiogenesis by preventing more reduction of VEGF gene expression in response to exercise. These improvements, in turn, increase left ventricular systolic function and decrease mortality in myocardial infarction rats. PMID- 26869869 TI - Functional near-infrared spectroscopy: a continuous wave type based system for human frontal lobe studies. AB - Functional Near-Infrared Spectroscopy (fNIRS) is an optical non-invasive brain monitoring technology that registers changes in hemodynamic responses within the cortex of the human brain. Over the last decades fNIRS became a promising method in neurosciences: it is non-invasive, portable and can be used in long term studies. All these advantages make it suitable for educational purposes as well. This paper presents basic methodological concept of optical engineering principles and suitable applications of fNIRS. We represent a continuous wave (cw fNIRS) system that could be used for frontal lobe studies in human adults or as demonstration equipment for physiological measurements. This system has been validated by comparing it with commercial device fNIR400 from Biopac. A comparison of geometry, data and statistical analyses suggests similar hemodynamic responses recorded by both devices. Our study suggests that this system can be used for further development and as a guideline for researchers to develop a specific tool for applications in human brain studies. PMID- 26869870 TI - Solid-Phase Synthesis of Molecularly Imprinted Polymer Nanoparticles with a Reusable Template - "Plastic Antibodies". AB - Molecularly Imprinted Polymers (MIPs) are generic alternatives to antibodies in sensors, diagnostics and separations. To displace biomolecules without radical changes in infrastructure in device manufacture, MIPs should share their characteristics (solubility, size, specificity and affinity, localized binding domain) whilst maintaining the advantages of MIPs (low-cost, short development time and high stability) hence the interest in MIP nanoparticles. Herein we report a reusable solid-phase template approach (fully compatible with automation) for the synthesis of MIP nanoparticles and their precise manufacture using a prototype automated UV photochemical reactor. Batches of nanoparticles (30-400 nm) with narrow size distributions imprinted with: melamine (d = 60 nm, Kd = 6.3 * 10-8 m), vancomycin (d = 250 nm, Kd = 3.4 * 10-9 m), a peptide (d = 350 nm, Kd = 4.8 * 10-8 m) and proteins have been produced. Our instrument uses a column packed with glass beads, bearing the template. Process parameters are under computer control, requiring minimal manual intervention. For the first time we demonstrate the reliable re-use of molecular templates in the synthesis of MIPs (>= 30 batches of nanoMIPs without loss of performance). NanoMIPs are produced template-free and the solid-phase acts both as template and affinity separation medium. PMID- 26869871 TI - Effects of smoking cessation on serum leptin and adiponectin levels. AB - BACKGROUND: Evidence on the association of leptin and adiponectin and smoking is limited and discordant. Leptin and adiponectin represent the most abundant adipokines in human plasma that play crucial roles in the pathophysiology of metabolic syndrome, atherosclerosis and insulin resistance. Leptin up-regulates the expression of several pro-inflammatory cytokines and is increased upon weight gain. Adiponectin has been shown to possess insulin sensitizing, anti inflammatory and anti-atherogenic properties and is increased upon weight reduction. Our aim was to assess the effects of smoking cessation on serum leptin and adiponectin levels. METHODS: We assessed the changes in serum leptin and adiponectin levels, serum CRP levels and BMI in apparently healthy smokers after 3 and 6 months of abstinence from smoking. Successful cessation was confirmed by an exhaled carbon monoxide measurement. 26 healthy non-smokers were recruited as controls. RESULTS: Among the sample group, 32 subjects had quitted smoking at 3 months and 29 subjects at 6 months. Samples' leptin increased significantly from baseline to three months (mean change 3.76 ng/ml [95 % CI 0.89, 6.64], p =0.012) and then decreased significantly from three to six months of smoking cessation (mean change -4,29 ng/ml [95 % CI -7.34, -6.64], p = 0.008). Samples' adiponectin increased significantly from baseline to three months of abstinence from smoking (mean change 2.34 [95 % CI -0.05, 4.73], p -0.05). BMI was significantly increased (mean change 2.03 kg/m(2) [95 % CI 1.60, 2.46], p <0.05), while CRP decreased significantly from baseline to 6 months of smoking cessation (mean change -0.68 mg/dl [95 % CI -1.06, -0.30], p = 0.001). CONCLUSIONS: Smoking quitters' leptin levels appear to increase 3 months after smoking cessation and then decrease from 3 to 6 months of abstinence from smoking. Adiponectin levels increase during the first trimester of smoking cessation. The decrease in CRP levels indicates that the low grade inflammation observed in smokers is gradually restored. The alterations of serum leptin and adiponectin after 6 months of smoking cessation suggest the same but do not reach statistically significant levels. Weight gain and changes in fat distribution may attenuate the beneficial effects of smoking cessation. PMID- 26869872 TI - Chronic Intermittent Hypoxia Alters Local Respiratory Circuit Function at the Level of the preBotzinger Complex. AB - Chronic intermittent hypoxia (CIH) is a common state experienced in several breathing disorders, including obstructive sleep apnea (OSA) and apneas of prematurity. Unraveling how CIH affects the CNS, and in turn how the CNS contributes to apneas is perhaps the most challenging task. The preBotzinger complex (preBotC) is a pre-motor respiratory network critical for inspiratory rhythm generation. Here, we test the hypothesis that CIH increases irregular output from the isolated preBotC, which can be mitigated by antioxidant treatment. Electrophysiological recordings from brainstem slices revealed that CIH enhanced burst-to-burst irregularity in period and/or amplitude. Irregularities represented a change in individual fidelity among preBotC neurons, and changed transmission from preBotC to the hypoglossal motor nucleus (XIIn), which resulted in increased transmission failure to XIIn. CIH increased the degree of lipid peroxidation in the preBotC and treatment with the antioxidant, 5,10,15,20-Tetrakis (1-methylpyridinium-4-yl)-21H,23H-porphyrin manganese(III) pentachloride (MnTMPyP), reduced CIH-mediated irregularities on the network rhythm and improved transmission of preBotC to the XIIn. These findings suggest that CIH promotes a pro-oxidant state that destabilizes rhythmogenesis originating from the preBotC and changes the local rhythm generating circuit which in turn, can lead to intermittent transmission failure to the XIIn. We propose that these CIH-mediated effects represent a part of the central mechanism that may perpetuate apneas and respiratory instability, which are hallmark traits in several dysautonomic conditions. PMID- 26869873 TI - Structural Brain Network Characteristics Can Differentiate CIS from Early RRMS. AB - Focal demyelinated lesions, diffuse white matter (WM) damage, and gray matter (GM) atrophy influence directly the disease progression in patients with multiple sclerosis. The aim of this study was to identify specific characteristics of GM and WM structural networks in subjects with clinically isolated syndrome (CIS) in comparison to patients with early relapsing-remitting multiple sclerosis (RRMS). Twenty patients with CIS, 33 with RRMS, and 40 healthy subjects were investigated using 3 T-MRI. Diffusion tensor imaging was applied, together with probabilistic tractography and fractional anisotropy (FA) maps for WM and cortical thickness correlation analysis for GM, to determine the structural connectivity patterns. A network topology analysis with the aid of graph theoretical approaches was used to characterize the network at different community levels (modularity, clustering coefficient, global, and local efficiencies). Finally, we applied support vector machines (SVM) to automatically discriminate the two groups. In comparison to CIS subjects, patients with RRMS were found to have increased modular connectivity and higher local clustering, highlighting increased local processing in both GM and WM. Both groups presented increased modularity and clustering coefficients in comparison to healthy controls. SVM algorithms achieved 97% accuracy using the clustering coefficient as classifier derived from GM and 65% using WM from probabilistic tractography and 67% from modularity of FA maps to differentiate between CIS and RRMS patients. We demonstrate a clear increase of modular and local connectivity in patients with early RRMS in comparison to CIS and healthy subjects. Based only on a single anatomic scan and without a priori information, we developed an automated and investigator-independent paradigm that can accurately discriminate between patients with these clinically similar disease entities, and could thus complement the current dissemination-in-time criteria for clinical diagnosis. PMID- 26869874 TI - Memory Efficient PCA Methods for Large Group ICA. AB - Principal component analysis (PCA) is widely used for data reduction in group independent component analysis (ICA) of fMRI data. Commonly, group-level PCA of temporally concatenated datasets is computed prior to ICA of the group principal components. This work focuses on reducing very high dimensional temporally concatenated datasets into its group PCA space. Existing randomized PCA methods can determine the PCA subspace with minimal memory requirements and, thus, are ideal for solving large PCA problems. Since the number of dataloads is not typically optimized, we extend one of these methods to compute PCA of very large datasets with a minimal number of dataloads. This method is coined multi power iteration (MPOWIT). The key idea behind MPOWIT is to estimate a subspace larger than the desired one, while checking for convergence of only the smaller subset of interest. The number of iterations is reduced considerably (as well as the number of dataloads), accelerating convergence without loss of accuracy. More importantly, in the proposed implementation of MPOWIT, the memory required for successful recovery of the group principal components becomes independent of the number of subjects analyzed. Highly efficient subsampled eigenvalue decomposition techniques are also introduced, furnishing excellent PCA subspace approximations that can be used for intelligent initialization of randomized methods such as MPOWIT. Together, these developments enable efficient estimation of accurate principal components, as we illustrate by solving a 1600-subject group-level PCA of fMRI with standard acquisition parameters, on a regular desktop computer with only 4 GB RAM, in just a few hours. MPOWIT is also highly scalable and could realistically solve group-level PCA of fMRI on thousands of subjects, or more, using standard hardware, limited only by time, not memory. Also, the MPOWIT algorithm is highly parallelizable, which would enable fast, distributed implementations ideal for big data analysis. Implications to other methods such as expectation maximization PCA (EM PCA) are also presented. Based on our results, general recommendations for efficient application of PCA methods are given according to problem size and available computational resources. MPOWIT and all other methods discussed here are implemented and readily available in the open source GIFT software. PMID- 26869875 TI - Spatial Noise in Coupling Strength and Natural Frequency within a Pacemaker Network; Consequences for Development of Intestinal Motor Patterns According to a Weakly Coupled Phase Oscillator Model. AB - Pacemaker activities generated by networks of interstitial cells of Cajal (ICC), in conjunction with the enteric nervous system, orchestrate most motor patterns in the gastrointestinal tract. It was our objective to understand the role of network features of ICC associated with the myenteric plexus (ICC-MP) in the shaping of motor patterns of the small intestine. To that end, a model of weakly coupled oscillators (oscillators influence each other's phase but not amplitude) was created with most parameters derived from experimental data. The ICC network is a uniform two dimensional network coupled by gap junctions. All ICC generate pacemaker (slow wave) activity with a frequency gradient in mice from 50/min at the proximal end of the intestine to 40/min at the distal end. Key features of motor patterns, directly related to the underlying pacemaker activity, are frequency steps and dislocations. These were accurately mimicked by reduction of coupling strength at a point in the chain of oscillators. When coupling strength was expressed as a product of gap junction density and conductance, and gap junction density was varied randomly along the chain (i.e., spatial noise) with a long-tailed distribution, plateau steps occurred at pointsof low density. As gap junction conductance was decreased, the number of plateaus increased, mimicking the effect of the gap junction inhibitor carbenoxolone. When spatial noise was added to the natural interval gradient, as gap junction conductance decreased, the number of plateaus increased as before but in addition the phase waves frequently changed direction of apparent propagation, again mimicking the effect of carbenoxolone. In summary, key features of the motor patterns that are governed by pacemaker activity may be a direct consequence of biological noise, specifically spatial noise in gap junction coupling and pacemaker frequency. PMID- 26869876 TI - Design and Analysis of a Neuromemristive Reservoir Computing Architecture for Biosignal Processing. AB - Reservoir computing (RC) is gaining traction in several signal processing domains, owing to its non-linear stateful computation, spatiotemporal encoding, and reduced training complexity over recurrent neural networks (RNNs). Previous studies have shown the effectiveness of software-based RCs for a wide spectrum of applications. A parallel body of work indicates that realizing RNN architectures using custom integrated circuits and reconfigurable hardware platforms yields significant improvements in power and latency. In this research, we propose a neuromemristive RC architecture, with doubly twisted toroidal structure, that is validated for biosignal processing applications. We exploit the device mismatch to implement the random weight distributions within the reservoir and propose mixed-signal subthreshold circuits for energy efficiency. A comprehensive analysis is performed to compare the efficiency of the neuromemristive RC architecture in both digital(reconfigurable) and subthreshold mixed-signal realizations. Both Electroencephalogram (EEG) and Electromyogram (EMG) biosignal benchmarks are used for validating the RC designs. The proposed RC architecture demonstrated an accuracy of 90 and 84% for epileptic seizure detection and EMG prosthetic finger control, respectively. PMID- 26869877 TI - A Toolkit for Orthogonal and in vivo Optical Manipulation of Ionotropic Glutamate Receptors. AB - The ability to optically manipulate specific neuronal signaling proteins with genetic precision paves the way for the dissection of their roles in brain function, behavior, and disease. Chemical optogenetic control with photoswitchable tethered ligands (PTLs) enables rapid, reversible and reproducible activation or block of specific neurotransmitter-gated receptors and ion channels in specific cells. In this study, we further engineered and characterized the light-activated GluK2 kainate receptor, LiGluR, to develop a toolbox of LiGluR variants. Low-affinity LiGluRs allow for efficient optical control of GluK2 while removing activation by native glutamate, whereas variant RNA edited versions enable the synaptic role of receptors with high and low Ca(2+) permeability to be assessed and spectral variant photoswitches provide flexibility in illumination. Importantly, we establish that LiGluR works efficiently in the cortex of awake, adult mice using standard optogenetic techniques, thus opening the door to probing the role of specific synaptic receptors and cellular signals in the neural circuit operations of the mammalian brain in normal conditions and in disease. The principals developed in this study are widely relevant to the engineering and in vivo use of optically controllable proteins, including other neurotransmitter receptors. PMID- 26869878 TI - Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress. PMID- 26869879 TI - Expression of Tgfbeta1 and Inflammatory Markers in the 6-hydroxydopamine Mouse Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by loss of midbrain dopaminergic (mDA) neurons in the substantia nigra (SN). Microglia-mediated neuroinflammation has been described as a common hallmark of PD and is believed to further trigger the progression of neurodegenerative events. Injections of 6-hydroxydopamine (6-OHDA) are widely used to induce degeneration of mDA neurons in rodents as an attempt to mimic PD and to study neurodegeneration, neuroinflammation as well as potential therapeutic approaches. In the present study, we addressed microglia and astroglia reactivity in the SN and the caudatoputamen (CPu) after 6-OHDA injections into the medial forebrain bundle (MFB), and further analyzed the temporal and spatial expression patterns of pro-inflammatory and anti-inflammatory markers in this mouse model of PD. We provide evidence that activated microglia as well as neurons in the lesioned SN and CPu express Transforming growth factor beta1 (Tgfbeta1), which overlaps with the downregulation of pro-inflammatory markers Tnfalpha, and iNos, and upregulation of anti-inflammatory markers Ym1 and Arg1. Taken together, the data presented in this study suggest an important role for Tgfbeta1 as a lesion associated factor that might be involved in regulating microglia activation states in the 6-OHDA mouse model of PD in order to prevent degeneration of uninjured neurons by microglia-mediated release of neurotoxic factors such as Tnfalpha and nitric oxide (NO). PMID- 26869881 TI - Fluoxetine Requires the Endfeet Protein Aquaporin-4 to Enhance Plasticity of Astrocyte Processes. AB - Morphological alterations in astrocytes are characteristic for post mortem brains of patients affected by major depressive disorder (MDD). Recently, a significant reduction in the coverage of blood vessels (BVs) by aquaporin-4 (AQP-4)-positive astrocyte endfeet has been shown in the prefrontal cortex (PFC) of MDD patients, suggesting that either alterations in the morphology of endfeet or in AQP-4 distribution might be responsible for the disease phenotype or constitute a consequence of its progress. Antidepressant drugs (ADs) regulate the expression of several proteins, including astrocyte-specific ones. Thus, they may target AQP 4 to induce morphological changes in astrocytes and restore their proper shape or relocate AQP-4 to endfeet. Using an animal model of depression, rats selectively bred for high anxiety-like behavior (HAB), we confirmed a reduced coverage of BVs in the adult PFC by AQP-4-immunoreactive (AQP-4-IR) astrocyte processes with respect to non-selected Wistar rats (NAB), thereby validating it for our study. A further evaluation of the morphology of astrocyte in brain slices (ex vivo) and in vitro using an antibody against the astrocyte-specific cytoskeletal protein glial fibrillary acidic protein (GFAP) revealed that HAB astrocytes extended less processes than NAB cells. Furthermore, short-term drug treatment in vitro with the AD fluoxetine (FLX) was sufficient to increase the plasticity of astrocyte processes, enhancing their number in NAB-derived cells and recovering their basal number in HAB-derived cells. This enhanced FLX-dependent plasticity occurred, however, only in the presence of intact AQP-4, as demonstrated by the lack of effect after the downregulation of AQP-4 with RNAi in both NAB and HAB cells. Nonetheless, a similar short-term treatment did neither modulate the coverage of BVs with AQP-4-positive astrocyte endfeet in NAB nor in HAB rats, although dosage and time of treatment were sufficient to fully recover GFAP expression in HAB brains. Thus, we suggest that longer treatment regimes may be needed to properly restore the coverage of BVs or to relocate AQP-4 to astrocyte endfeet. In conclusion, FLX requires AQP-4 to modulate the plasticity of astrocyte processes and this effect might be essential to re-establish a functional glia-vasculature interface necessary for a physiological communication between bloodstream and brain parenchyma. PMID- 26869880 TI - Overexpression of Isoforms of Nitric Oxide Synthase 1 Adaptor Protein, Encoded by a Risk Gene for Schizophrenia, Alters Actin Dynamics and Synaptic Function. AB - Proper communication between neurons depends upon appropriate patterning of dendrites and correct distribution and structure of spines. Schizophrenia is a neuropsychiatric disorder characterized by alterations in dendrite branching and spine density. Nitric oxide synthase 1 adaptor protein (NOS1AP), a risk gene for schizophrenia, encodes proteins that are upregulated in the dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia. To elucidate the effects of NOS1AP overexpression observed in individuals with schizophrenia, we investigated changes in actin dynamics and spine development when a long (NOS1AP L) or short (NOS1AP-S) isoform of NOS1AP is overexpressed. Increased NOS1AP-L protein promotes the formation of immature spines when overexpressed in rat cortical neurons from day in vitro (DIV) 14 to DIV 17 and reduces the amplitude of miniature excitatory postsynaptic currents (mEPSCs). In contrast, increased NOS1AP-S protein increases the rate of actin polymerization and the number of immature and mature spines, which may be attributed to a decrease in total Rac1 expression and a reduction in the levels of active cofilin. The increase in the number of mature spines by overexpression of NOS1AP-S is accompanied by an increase in the frequency of mEPSCs. Our findings show that overexpression of NOS1AP-L or NOS1AP-S alters the actin cytoskeleton and synaptic function. However, the mechanisms by which these isoforms induce these changes are distinct. These results are important for understanding how increased expression of NOS1AP isoforms can influence spine development and synaptic function. PMID- 26869882 TI - How to Properly Measure a Current-Voltage Relation?-Interpolation vs. Ramp Methods Applied to Studies of GABAA Receptors. AB - The relation between current and voltage, I-V relation, is central to functional analysis of membrane ion channels. A commonly used method, since the introduction of the voltage-clamp technique, to establish the I-V relation depends on the interpolation of current amplitudes recorded at different steady voltages. By a theoretical computational approach as well as by experimental recordings from GABAA-receptor mediated currents in mammalian central neurons, we here show that this interpolation method may give reversal potentials and conductances that do not reflect the properties of the channels studied under conditions when ion flux may give rise to concentration changes. Therefore, changes in ion concentrations may remain undetected and conclusions on changes in conductance, such as during desensitization, may be mistaken. In contrast, an alternative experimental approach, using rapid voltage ramps, enable I-V relations that much better reflect the properties of the studied ion channels. PMID- 26869883 TI - Genetic Deletion of TREK-1 or TWIK-1/TREK-1 Potassium Channels does not Alter the Basic Electrophysiological Properties of Mature Hippocampal Astrocytes In Situ. AB - We have recently shown that a linear current-to-voltage (I-V) relationship of membrane conductance (passive conductance) reflects the intrinsic property of K(+) channels in mature astrocytes. While passive conductance is known to underpin a highly negative and stable membrane potential (V M) essential for the basic homeostatic function of astrocytes, a complete repertoire of the involved K(+) channels remains elusive. TREK-1 two-pore domain K(+) channel (K2P) is highly expressed in astrocytes, and covalent association of TREK-1 with TWIK-1, another highly expressed astrocytic K2P, has been reported as a mechanism underlying the trafficking of heterodimer TWIK-1/TREK-1 channel to the membrane and contributing to astrocyte passive conductance. To decipher the individual contribution of TREK-1 and address whether the appearance of passive conductance is conditional to the co-expression of TWIK-1/TREK-1 in astrocytes, TREK-1 single and TWIK-1/TREK-1 double gene knockout mice were used in the present study. The relative quantity of mRNA encoding other astrocyte K(+) channels, such as Kir4.1, Kir5.1, and TREK-2, was not altered in these gene knockout mice. Whole-cell recording from hippocampal astrocytes in situ revealed no detectable changes in astrocyte passive conductance, V M, or membrane input resistance (R in) in either kind of gene knockout mouse. Additionally, TREK-1 proteins were mainly located in the intracellular compartments of the hippocampus. Altogether, genetic deletion of TREK-1 alone or together with TWIK-1 produced no obvious alteration in the basic electrophysiological properties of hippocampal astrocytes. Thus, future research focusing on other K(+) channels may shed light on this long-standing and important question in astrocyte physiology. PMID- 26869884 TI - BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume. AB - The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia, and allowed to recover for 24 h. Infarct volumes and functional outcome were assessed and the inflammatory response was evaluated using immunofluorescence, Western blotting, quantitative PCR (qPCR) and Mesoscale multiplex analysis. We observed no difference in the infarct volume or neurological outcome between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia in vivo. However, this is not translated into a robust neuroprotection in vivo. PMID- 26869885 TI - Rescue of Cyclic AMP Mediated Long Term Potentiation Impairment in the Hippocampus of Mecp2 Knockout (Mecp2(-/y) ) Mice by Rolipram. AB - Rett syndrome (RTT) patients experience learning difficulties and memory loss. Analogous deficits of hippocampal plasticity are reported in mouse models of RTT. To elucidate the underlying pathophysiology, we studied long term potentiation (LTP) at the CA3 to CA1 synapses in the hippocampus in acute brain slices from WT and Mecp2(-/y) mice, by either activating cAMP dependent pathway or using high frequency stimulation, by means of patch clamp. We have observed that, the NMDA channel current characteristics remain unchanged in the Mecp2(-/y) mice. The adenylyl cyclase (AC) agonist forskolin evoked a long lasting potentiation of evoked EPSCs in WT CA1 neurons, but only minimally enhanced the EPSCs in the Mecp2(-/y) mice. This weaker potentiation in Mecp2 (-/) (y) mice was ameliorated by application of phosphodiesterase 4 inhibitor rolipram. The hyperpolarization activated cyclic nucleotide gated channel current (I h) was potentiated to similar extent by forskolin in both phenotypes. Multiple tetanus induced cAMP dependent plasticity was also impaired in the Mecp2 (-/) (y) mice, and was also partially rescued by rolipram. Western blot analysis of CA region of Mecp2 (-/) (y) mice hippocampus revealed more than twofold up-regulation of protein kinase A (PKA) regulatory subunits, while the expression of the catalytic subunit remained unchanged. We hypothesize that the overexpressed PKA regulatory subunits buffer cAMP and restrict the PKA mediated phosphorylation of target proteins necessary for LTP. Blocking the degradation of cAMP, thereby saturating the regulatory subunits alleviated this defect. PMID- 26869886 TI - Through the Immune Looking Glass: A Model for Brain Memory Strategies. AB - The immune system (IS) and the central nervous system (CNS) are complex cognitive networks involved in defining the identity (self) of the individual through recognition and memory processes that enable one to anticipate responses to stimuli. Brain memory has traditionally been classified as either implicit or explicit on psychological and anatomical grounds, with reminiscences of the evolutionarily-based innate-adaptive IS responses. Beyond the multineuronal networks of the CNS, we propose a theoretical model of brain memory integrating the CNS as a whole. This is achieved by analogical reasoning between the operational rules of recognition and memory processes in both systems, coupled to an evolutionary analysis. In this new model, the hippocampus is no longer specifically ascribed to explicit memory but rather it both becomes part of the innate (implicit) memory system and tightly controls the explicit memory system. Alike the antigen presenting cells for the IS, the hippocampus would integrate transient and pseudo-specific (i.e., danger-fear) memories and would drive the formation of long-term and highly specific or explicit memories (i.e., the taste of the Proust's madeleine cake) by the more complex and recent, evolutionarily speaking, neocortex. Experimental and clinical evidence is provided to support the model. We believe that the singularity of this model's approximation could help to gain a better understanding of the mechanisms operating in brain memory strategies from a large-scale network perspective. PMID- 26869888 TI - Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression. AB - Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses. PMID- 26869887 TI - Brain and Retinal Pericytes: Origin, Function and Role. AB - Pericytes are specialized mural cells located at the abluminal surface of capillary blood vessels, embedded within the basement membrane. In the vascular network these multifunctional cells fulfil diverse functions, which are indispensable for proper homoeostasis. They serve as microvascular stabilizers, are potential regulators of microvascular blood flow and have a central role in angiogenesis, as they for example regulate endothelial cell proliferation. Furthermore, pericytes, as part of the neurovascular unit, are a major component of the blood-retina/brain barrier. CNS pericytes are a heterogenic cell population derived from mesodermal and neuro-ectodermal germ layers acting as modulators of stromal and niche environmental properties. In addition, they display multipotent differentiation potential making them an intriguing target for regenerative therapies. Pericyte-deficiencies can be cause or consequence of many kinds of diseases. In diabetes, for instance, pericyte-loss is a severe pathological process in diabetic retinopathy (DR) with detrimental consequences for eye sight in millions of patients. In this review, we provide an overview of our current understanding of CNS pericyte origin and function, with a special focus on the retina in the healthy and diseased. Finally, we highlight the role of pericytes in de- and regenerative processes. PMID- 26869889 TI - Short-Term Synaptic Plasticity at Interneuronal Synapses Could Sculpt Rhythmic Motor Patterns. AB - The output of a neuronal network depends on the organization and functional properties of its component cells and synapses. While the characterization of synaptic properties has lagged cellular analyses, a potentially important aspect in rhythmically active networks is how network synapses affect, and are in turn affected by, network activity. This could lead to a potential circular interaction where short-term activity-dependent synaptic plasticity is both influenced by and influences the network output. The analysis of synaptic plasticity in the lamprey locomotor network was extended here to characterize the short-term plasticity of connections between network interneurons and to try and address its potential network role. Paired recordings from identified interneurons in quiescent networks showed synapse-specific synaptic properties and plasticity that supported the presence of two hemisegmental groups that could influence bursting: depression in an excitatory interneuron group, and facilitation in an inhibitory feedback circuit. The influence of activity dependent synaptic plasticity on network activity was investigated experimentally by changing Ringer Ca(2+) levels, and in a simple computer model. A potential caveat of the experimental analyses was that changes in Ringer Ca(2+) (and compensatory adjustments in Mg(2+) in some cases) could alter several other cellular and synaptic properties. Several of these properties were tested, and while there was some variability, these were not usually significantly affected by the Ringer changes. The experimental analyses suggested that depression of excitatory inputs had the strongest influence on the patterning of network activity. The simulation supported a role for this effect, and also suggested that the inhibitory facilitating group could modulate the influence of the excitatory synaptic depression. Short-term activity-dependent synaptic plasticity has not generally been considered in spinal cord models. These results provide further evidence for short-term plasticity between locomotor network interneurons. As this plasticity could influence the patterning of the network output it should be considered as a potential functional component of spinal cord networks. PMID- 26869890 TI - Natural Vocalizations in the Mammalian Inferior Colliculus are Broadly Encoded by a Small Number of Independent Multi-Units. AB - How complex natural sounds are represented by the main converging center of the auditory midbrain, the central inferior colliculus, is an open question. We applied neural discrimination to determine the variation of detailed encoding of individual vocalizations across the best frequency gradient of the central inferior colliculus. The analysis was based on collective responses from several neurons. These multi-unit spike trains were recorded from guinea pigs exposed to a spectrotemporally rich set of eleven species-specific vocalizations. Spike trains of disparate units from the same recording were combined in order to investigate whether groups of multi-unit clusters represent the whole set of vocalizations more reliably than only one unit, and whether temporal response correlations between them facilitate an unambiguous neural representation of the vocalizations. We found a spatial distribution of the capability to accurately encode groups of vocalizations across the best frequency gradient. Different vocalizations are optimally discriminated at different locations of the best frequency gradient. Furthermore, groups of a few multi-unit clusters yield improved discrimination over only one multi-unit cluster between all tested vocalizations. However, temporal response correlations between units do not yield better discrimination. Our study is based on a large set of units of simultaneously recorded responses from several guinea pigs and electrode insertion positions. Our findings suggest a broadly distributed code for behaviorally relevant vocalizations in the mammalian inferior colliculus. Responses from a few non-interacting units are sufficient to faithfully represent the whole set of studied vocalizations with diverse spectrotemporal properties. PMID- 26869892 TI - Principles of Intelligence: On Evolutionary Logic of the Brain. AB - Humans and animals may encounter numerous events, objects, scenes, foods and countless social interactions in a lifetime. This means that the brain is constructed by evolution to deal with uncertainties and various possibilities. What is the architectural abstraction of intelligence that enables the brain to discover various possible patterns and knowledge about complex, evolving worlds? Here, I discuss the Theory of Connectivity-a "power-of-two" based, operational principle that can serve as a unified wiring and computational logic for organizing and constructing cell assemblies into the microcircuit-level building block, termed as functional connectivity motif (FCM). Defined by the power-of-two based equation, N = 2 (i) -1, each FCM consists of the principal projection neuron cliques (N), ranging from those specific cliques receiving specific information inputs (i) to those general and sub-general cliques receiving various combinatorial convergent inputs. As the evolutionarily conserved logic, its validation requires experimental demonstrations of the following three major properties: (1) Anatomical prevalence-FCMs are prevalent across neural circuits, regardless of gross anatomical shapes; (2) Species conservancy-FCMs are conserved across different animal species; and (3) Cognitive universality-FCMs serve as a universal computational logic at the cell assembly level for processing a variety of cognitive experiences and flexible behaviors. More importantly, this Theory of Connectivity further predicts that the specific-to-general combinatorial connectivity pattern within FCMs should be preconfigured by evolution, and emerge innately from development as the brain's computational primitives. This proposed design-principle can also explain the general purpose of the layered cortex and serves as its core computational algorithm. PMID- 26869893 TI - Mathematical Modeling in Neuroscience: Neuronal Activity and Its Modulation by Astrocytes. PMID- 26869891 TI - Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy. AB - Spinal muscular atrophy (SMA) is a recessive autosomal neuromuscular disease, representing the most common fatal pediatric pathology. Even though, classically and in a simplistic way, it is categorized as a motor neuron (MN) disease, there is an increasing general consensus that its pathogenesis is more complex than expected. In particular, neuromuscular junctions (NMJs) are affected by dramatic alterations, including immaturity, denervation and neurofilament accumulation, associated to impaired synaptic functions: these abnormalities may in turn have a detrimental effect on MN survival. Here, we provide a description of NMJ development/maintenance/maturation in physiological conditions and in SMA, focusing on pivotal molecules and on the time-course of pathological events. Moreover, since NMJs could represent an important target to be exploited for counteracting the pathology progression, we also describe several therapeutic strategies that, directly or indirectly, aim at NMJs. PMID- 26869894 TI - Damage to Fronto-Parietal Networks Impairs Motor Imagery Ability after Stroke: A Voxel-Based Lesion Symptom Mapping Study. AB - BACKGROUND: Mental practice with motor imagery has been shown to promote motor skill acquisition in healthy subjects and patients. Although lesions of the common motor imagery and motor execution neural network are expected to impair motor imagery ability, functional equivalence appears to be at least partially preserved in stroke patients. AIM: To identify brain regions that are mandatory for preserved motor imagery ability after stroke. METHOD: Thirty-seven patients with hemiplegia after a first time stroke participated. Motor imagery ability was measured using a Motor Imagery questionnaire and temporal congruence test. A voxelwise lesion symptom mapping approach was used to identify neural correlates of motor imagery in this cohort within the first year post-stroke. RESULTS: Poor motor imagery vividness was associated with lesions in the left putamen, left ventral premotor cortex and long association fibers linking parieto-occipital regions with the dorsolateral premotor and prefrontal areas. Poor temporal congruence was otherwise linked to lesions in the more rostrally located white matter of the superior corona radiata. CONCLUSION: This voxel-based lesion symptom mapping study confirms the association between white matter tract lesions and impaired motor imagery ability, thus emphasizing the importance of an intact fronto-parietal network for motor imagery. Our results further highlight the crucial role of the basal ganglia and premotor cortex when performing motor imagery tasks. PMID- 26869895 TI - Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio. AB - In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress. PMID- 26869896 TI - Network-Based Analysis Reveals Functional Connectivity Related to Internet Addiction Tendency. AB - Preoccupation and compulsive use of the internet can have negative psychological effects, such that it is increasingly being recognized as a mental disorder. The present study employed network-based statistics to explore how whole-brain functional connections at rest is related to the extent of individual's level of internet addiction, indexed by a self-rated questionnaire. We identified two topologically significant networks, one with connections that are positively correlated with internet addiction tendency, and one with connections negatively correlated with internet addiction tendency. The two networks are interconnected mostly at frontal regions, which might reflect alterations in the frontal region for different aspects of cognitive control (i.e., for control of internet usage and gaming skills). Next, we categorized the brain into several large regional subgroupings, and found that the majority of proportions of connections in the two networks correspond to the cerebellar model of addiction which encompasses the four-circuit model. Lastly, we observed that the brain regions with the most inter-regional connections associated with internet addiction tendency replicate those often seen in addiction literature, and is corroborated by our meta analysis of internet addiction studies. This research provides a better understanding of large-scale networks involved in internet addiction tendency and shows that pre-clinical levels of internet addiction are associated with similar regions and connections as clinical cases of addiction. PMID- 26869897 TI - Impaired Communication Between the Dorsal and Ventral Stream: Indications from Apraxia. AB - Patients with apraxia perform poorly when demonstrating how an object is used, particularly when pantomiming the action. However, these patients are able to accurately identify, and to pick up and move objects, demonstrating intact ventral and dorsal stream visuomotor processing. Appropriate object manipulation for skilled use is thought to rely on integration of known and visible object properties associated with "ventro-dorsal" stream neural processes. In apraxia, it has been suggested that stored object knowledge from the ventral stream may be less readily available to incorporate into the action plan, leading to an over reliance on the objects' visual affordances in object-directed motor behavior. The current study examined grasping performance in left hemisphere stroke patients with (N = 3) and without (N = 9) apraxia, and in age-matched healthy control participants (N = 14), where participants repeatedly grasped novel cylindrical objects of varying weight distribution. Across two conditions, object weight distribution was indicated by either a memory-associated cue (object color) or visual-spatial cue (visible dot over the weighted end). Participants were required to incorporate object-weight associations to effectively grasp and balance each object. Control groups appropriately adjusted their grasp according to each object's weight distribution across each condition, whereas throughout the task two of the three apraxic patients performed poorly on both the memory associated and visual-spatial cue conditions. A third apraxic patient seemed to compensate for these difficulties but still performed differently to control groups. Patients with apraxia performed normally on the neutral control condition when grasping the evenly weighted version. The pattern of behavior in apraxic patients suggests impaired integration of visible and known object properties attributed to the ventro-dorsal stream: in learning to grasp the weighted object accurately, apraxic patients applied neither pure knowledge-based information (the memory-associated condition) nor higher-level information given in the visual-spatial cue condition. Disruption to ventro-dorsal stream predicts that apraxic patients will have difficulty learning to manipulate new objects on the basis of information other than low-level visual cues such as shape and size. PMID- 26869898 TI - Modification of Brain Oscillations via Rhythmic Light Stimulation Provides Evidence for Entrainment but Not for Superposition of Event-Related Responses. AB - The functional relevance of brain oscillations in the alpha frequency range (8-13 Hz) has been repeatedly investigated through the use of rhythmic visual stimulation. The underlying mechanism of the steady-state visual evoked potential (SSVEP) measured in EEG during rhythmic stimulation, however, is not known. There are two hypotheses on the origin of SSVEPs: entrainment of brain oscillations and superposition of event-related responses (ERPs). The entrainment but not the superposition hypothesis justifies rhythmic visual stimulation as a means to manipulate brain oscillations, because superposition assumes a linear summation of single responses, independent from ongoing brain oscillations. Here, we stimulated participants with a rhythmic flickering light of different frequencies and intensities. We measured entrainment by comparing the phase coupling of brain oscillations stimulated by rhythmic visual flicker with the oscillations induced by arrhythmic jittered stimulation, varying the time, stimulation frequency, and intensity conditions. In line with a theoretical concept of entrainment (the so called Arnold tongue), we found the phase coupling to be more pronounced with increasing stimulation intensity as well as at stimulation frequencies closer to each participant's intrinsic frequency. Only inside the Arnold tongue did the conditions significantly differ from the jittered stimulation. Furthermore, even in a single sequence of an SSVEP, we found non-linear features (intermittency of phase locking) that contradict the linear summation of single responses, as assumed by the superposition hypothesis. Our findings provide unequivocal evidence that visual rhythmic stimulation entrains brain oscillations, thus validating the approach of rhythmic stimulation as a manipulation of brain oscillations. PMID- 26869899 TI - Resting-State Functional Magnetic Resonance Imaging for Language Preoperative Planning. AB - Functional magnetic resonance imaging (fMRI) is a well-known non-invasive technique for the study of brain function. One of its most common clinical applications is preoperative language mapping, essential for the preservation of function in neurosurgical patients. Typically, fMRI is used to track task-related activity, but poor task performance and movement artifacts can be critical limitations in clinical settings. Recent advances in resting-state protocols open new possibilities for pre-surgical mapping of language potentially overcoming these limitations. To test the feasibility of using resting-state fMRI instead of conventional active task-based protocols, we compared results from fifteen patients with brain lesions while performing a verb-to-noun generation task and while at rest. Task-activity was measured using a general linear model analysis and independent component analysis (ICA). Resting-state networks were extracted using ICA and further classified in two ways: manually by an expert and by using an automated template matching procedure. The results revealed that the automated classification procedure correctly identified language networks as compared to the expert manual classification. We found a good overlay between task-related activity and resting-state language maps, particularly within the language regions of interest. Furthermore, resting-state language maps were as sensitive as task-related maps, and had higher specificity. Our findings suggest that resting-state protocols may be suitable to map language networks in a quick and clinically efficient way. PMID- 26869900 TI - Effective Connectivity within the Default Mode Network: Dynamic Causal Modeling of Resting-State fMRI Data. AB - The Default Mode Network (DMN) is a brain system that mediates internal modes of cognitive activity, showing higher neural activation when one is at rest. Nowadays, there is a lot of interest in assessing functional interactions between its key regions, but in the majority of studies only association of Blood-oxygen level dependent (BOLD) activation patterns is measured, so it is impossible to identify causal influences. There are some studies of causal interactions (i.e., effective connectivity), however often with inconsistent results. The aim of the current work is to find a stable pattern of connectivity between four DMN key regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), left and right intraparietal cortex (LIPC and RIPC). For this purpose functional magnetic resonance imaging (fMRI) data from 30 healthy subjects (1000 time points from each one) was acquired and spectral dynamic causal modeling (DCM) on a resting-state fMRI data was performed. The endogenous brain fluctuations were explicitly modeled by Discrete Cosine Set at the low frequency band of 0.0078-0.1 Hz. The best model at the group level is the one where connections from both bilateral IPC to mPFC and PCC are significant and symmetrical in strength (p < 0.05). Connections between mPFC and PCC are bidirectional, significant in the group and weaker than connections originating from bilateral IPC. In general, all connections from LIPC/RIPC to other DMN regions are much stronger. One can assume that these regions have a driving role within the DMN. Our results replicate some data from earlier works on effective connectivity within the DMN as well as provide new insights on internal DMN relationships and brain's functioning at resting state. PMID- 26869901 TI - Viewing Instructions Accompanying Action Observation Modulate Corticospinal Excitability. AB - Action observation interventions may have the potential to contribute to improved motor function in motor (re)learning settings by promoting functional activity and plasticity in the motor regions of the brain. Optimal methods for delivering such interventions, however, have yet to be established. This experiment investigated the effect on corticospinal excitability of manipulating the viewing instructions provided to participants (N = 21) prior to action observation. Specifically, motor evoked potential responses measured from the right hand muscles following single-pulse transcranial magnetic stimulation (TMS) to the left motor cortex were compared when participants were instructed to observe finger-thumb opposition movement sequences: (i) passively; (ii) with the intent to imitate the observed movement; or (iii) whilst simultaneously and actively imagining that they were performing the movement as they observed it. All three action observation viewing instructions facilitated corticospinal excitability to a greater extent than did observation of a static hand. In addition, the extent to which corticospinal excitability was facilitated was greater during combined observation and imagery, compared to passive observation. These findings have important implications for the design of action observation interventions in motor (re)learning settings, where instructions that encourage observers to simultaneously imagine themselves performing the observed movement may offer the current optimal method for improving motor function through action observation. PMID- 26869902 TI - Bilateral Knee Extensor Fatigue Modulates Force and Responsiveness of the Corticospinal Pathway in the Non-fatigued, Dominant Elbow Flexors. AB - Exercise-induced fatigue affects muscle performance and modulates corticospinal excitability in non-exercised muscles. The purpose of this study was to investigate the effect of bilateral knee extensor fatigue on dominant elbow flexor (EF) maximal voluntary force production and corticospinal excitability. Transcranial magnetic, transmastoid electrical and brachial plexus electrical stimulation (BPES) were used to investigate corticospinal, spinal, and muscle excitability of the dominant EF before and after a bilateral knee extensor fatiguing protocol or time matched rest period (control). For both sessions three stimuli were delivered every 1.5 s during the three pre-test time points and during the 1st, 3rd, 6th, 9th and 12th post-test 5 s EF isometric maximal voluntary contractions (MVC). In both conditions, overall, EF MVC force (p < 0.001) decreased progressively from repetition #1 to #12 during the post-test MVC protocol. EF MVC force (p < 0.001, ES = 0.9, Delta10.3%) decrements were more pronounced in the knee extensor fatigue intervention condition. In addition, there were no significant differences between conditions for biceps brachii electromyographic (EMG) activity (p = 0.43), motor evoked potentials (MEPs) amplitude (p = 0.908) or MEP silent period (SP; p = 0.776). However, the fatigue condition exhibited a lower MEP/cervicomedullary MEP (CMEP) ratio (p = 0.042, ES = 2.5, Delta25%) and a trend toward higher CMEP values (p = 0.08, ES = 0.5, Delta20.4%). These findings suggest that bilateral knee extensor fatigue can impair performance and modulate corticospinal excitability of the EF. PMID- 26869903 TI - A Comparative Study of the Impact of Theta-Burst and High-Frequency Stimulation on Memory Performance. AB - The transformation of the information stored in the working memory into the system of long-term memory depends on the physiological mechanism, long-term potential (LTP). In a large number of experimental studies, theta-burst stimulation (TBS) and high-frequency stimulation (HFS) are LTP induction protocols. However, they have not been adapted to the model related to memory. In this paper, the improved Camperi-Wang (C-W) model with Ca(2+) subsystem-induced bi-stability was adopted, and TBS and HFS were simulated to act as the initial stimuli of this working memory model. Evaluating the influence of stimuli properties (cycle, amplitude, duty ration) on memory mechanism of the model, it is found that both TBS and HFS can be adopted to activate working memory model and produce long-term memory. Moreover, the different impacts of two types of stimuli on the formation of long-term memory were analyzed as well. Thus, the importance of this study lies firstly in describing the link and interaction between working memory and long-term memory from the quantitative view, which provides a theoretical basis for the study of neural dynamics mechanism of long term memory formation in the future. PMID- 26869905 TI - General Markers of Conscious Visual Perception and Their Timing. AB - Previous studies have observed different onset times for the neural markers of conscious perception. This variability could be attributed to procedural differences between studies. Here we show that the onset times for the markers of conscious visual perception can strongly vary even within a single study. A heterogeneous stimulus set was presented at threshold contrast. Trials with and without conscious perception were contrasted on 100 balanced subsets of the data. Importantly, the 100 subsets with heterogeneous stimuli did not differ in stimulus content, but only with regard to specific trials used. This approach enabled us to study general markers of conscious visual perception independent of stimulus content, characterize their onset and its variability within one study. N200 and P300 were the two reliable markers of conscious visual perception common to all perceived stimuli and absent for all non-perceived stimuli. The estimated mean onset latency for both markers was shortly after 200 ms. However, the onset latency of these markers was associated with considerable variability depending on which subsets of the data were considered. We show that it is first and foremost the amplitude fluctuation in the condition without conscious perception that explains the observed variability in onset latencies of the markers of conscious visual perception. PMID- 26869904 TI - The Interface between Neuroscience and Neuro-Psychoanalysis: Focus on Brain Connectivity. AB - Over the past 20 years, the advent of advanced techniques has significantly enhanced our knowledge on the brain. Yet, our understanding of the physiological and pathological functioning of the mind is still far from being exhaustive. Both the localizationist and the reductionist neuroscientific approaches to psychiatric disorders have proven to be largely unsatisfactory and are outdated. Accruing evidence suggests that psychoanalysis can engage the neurosciences in a productive and mutually enriching dialogue that may further our understanding of psychiatric disorders. In particular, advances in brain connectivity research have provided evidence supporting the convergence of neuroscientific findings and psychoanalysis and helped characterize the circuitry and mechanisms that underlie higher brain functions. In the present paper we discuss how knowledge on brain connectivity can impact neuropsychoanalysis, with a particular focus on schizophrenia. Brain connectivity studies in schizophrenic patients indicate complex alterations in brain functioning and circuitry, with particular emphasis on the role of cortical midline structures (CMS) and the default mode network (DMN). These networks seem to represent neural correlates of psychodynamic concepts central to the understanding of schizophrenia and of core psychopathological alterations of this disorder (i.e., ego disturbances and impaired primary process thinking). PMID- 26869906 TI - Does Rubella Cause Autism: A 2015 Reappraisal? AB - In the 1970s, Stella Chess found a high prevalence of autism in children with congenital rubella syndrome (CRS), 200 times that of the general population at the time. Many researchers quote this fact to add proof to the current theory that maternal infection with immune system activation in pregnancy leads to autism in the offspring. This rubella and autism association is presented with the notion that rubella has been eliminated in today's world. CRS cases are no longer typically seen; yet, autistic children often share findings of CRS including deafness, congenital heart defects, and to a lesser extent visual changes. Autistic children commonly have hyperactivity and spasticity, as do CRS children. Both autistic and CRS individuals may develop type 1 diabetes as young adults. Neuropathology of CRS infants may reveal cerebral vasculitis with narrowed lumens and cerebral necrosis. Neuroradiological findings of children with CRS show calcifications, periventricular leukomalacia, and dilated perivascular spaces. Neuroradiology of autism has also demonstrated hyperintensities, leukomalacia, and prominent perivascular spaces. PET studies of autistic individuals exhibit decreased perfusion to areas of the brain similarly affected by rubella. In both autism and CRS, certain changes in the brain have implicated the immune system. Several children with autism lack antibodies to rubella, as do children with CRS. These numerous similarities increase the probability of an association between rubella virus and autism. Rubella and autism cross many ethnicities in many countries. Contrary to current belief, rubella has not been eradicated and globally affects up to 5% of pregnant women. Susceptibility continues as vaccines are not given worldwide and are not fully protective. Rubella might still cause autism, even in vaccinated populations. PMID- 26869907 TI - Amplitude of Low-Frequency Fluctuations in Multiple-Frequency Bands in Acute Mild Traumatic Brain Injury. AB - Functional disconnectivity during the resting state has been observed in mild traumatic brain injury (mTBI) patients during the acute stage. However, it remains largely unknown whether the abnormalities are related to specific frequency bands of the low-frequency oscillations (LFO). Here, we used the amplitude of low-frequency fluctuations (ALFF) to examine the amplitudes of LFO in different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and typical: 0.01-0.08 Hz) in patients with acute mTBI. A total of 24 acute mTBI patients and 24 age-, sex-, and education-matched healthy controls participated in this study. In the typical band, acute mTBI patients showed lower standardized ALFF in the right middle frontal gyrus and higher standardized ALFF in the right lingual/fusiform gyrus and left middle occipital gyrus. Further analyses showed that the difference between groups was concentrated in a narrower (slow-4) frequency band. In the slow-5 band, mTBI patients only exhibited higher standardized ALFF in the occipital areas. No significant correlation between the mini-mental state examination score and the standardized ALFF value was found in any brain region in the three frequency bands. Finally, no significant interaction between frequency bands and groups was found in any brain region. We concluded that the abnormality of spontaneous brain activity in acute mTBI patients existed in the frontal lobe as well as in distributed brain regions associated with integrative, sensory, and emotional roles, and the abnormal spontaneous neuronal activity in different brain regions could be better detected by the slow-4 band. These findings might contribute to a better understanding of local neural psychopathology of acute mTBI. Future studies should take the frequency bands into account when measuring intrinsic brain activity of mTBI patients. PMID- 26869908 TI - Involvement of the Ventrolateral Prefrontal Cortex in Learning Others' Bad Reputations and Indelible Distrust. AB - A bad reputation can persistently affect judgments of an individual even when it turns out to be invalid and ought to be disregarded. Such indelible distrust may reflect that the negative evaluation elicited by a bad reputation transfers to a person. Consequently, the person him/herself may come to activate this negative evaluation irrespective of the accuracy of the reputation. If this theoretical model is correct, an evaluation-related brain region will be activated when witnessing a person whose bad reputation one has learned about, regardless of whether the reputation is deemed valid or not. Here, we tested this neural hypothesis with functional magnetic resonance imaging (fMRI). Participants memorized faces paired with either a good or a bad reputation. Next, they viewed the faces alone and inferred whether each person was likely to cooperate, first while retrieving the reputations, and then while trying to disregard them as false. A region of the left ventrolateral prefrontal cortex (vlPFC), which may be involved in negative evaluation, was activated by faces previously paired with bad reputations, irrespective of whether participants attempted to retrieve or disregard these reputations. Furthermore, participants showing greater activity of the left ventrolateral prefrontal region in response to the faces with bad reputations were more likely to infer that these individuals would not cooperate. Thus, once associated with a bad reputation, a person may elicit evaluation related brain responses on their own, thereby evoking distrust independently of their reputation. PMID- 26869909 TI - Modulation of Cortical Inhibitory Circuits after Cathodal Transcranial Direct Current Stimulation over the Primary Motor Cortex. AB - Here, we aimed to evaluate whether cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) and primary somatosensory cortex (S1) can modulate cortical inhibitory circuits. Sixteen healthy subjects participated in this study. Cathodal tDCS was positioned over the left M1 (M1 cathodal) or left S1 (S1 cathodal) with an intensity of 1 mA for 10 min. Sham tDCS was applied for 10 min over the left M1 (sham). Motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were recorded from the right abductor pollicis brevis (APB) muscle before the intervention (pre) and 10 and 30 min after the intervention (post 1 and post 2, respectively). Cortical inhibitory circuits were evaluated using short-interval intracortical inhibition (SICI) and short-latency afferent inhibition (SAI). M1 cathodal decreased single pulse MEP amplitudes at post 1 and decreased SAI at post 1 and post 2; however, SICI did not exhibit any change. S1 cathodal and sham did not show any changes in MEP amplitudes at any of the three time points. These results demonstrated that cathodal tDCS over the M1 not only decreases the M1 excitability but also affects the cortical inhibitory circuits related to SAI. PMID- 26869910 TI - Commentary: Lessons from the Analysis of Non-human Primates for Understanding Human Aging and Neurodegenerative Diseases. PMID- 26869911 TI - 1-Hz Repetitive Transcranial Magnetic Stimulation over the Posterior Parietal Cortex Modulates Spatial Attention. AB - Lesion and neuroimaging studies have suggested that regions in the posterior parietal cortex (PPC) are involved in visual spatial attention. The aim of this study was to investigate the potential effects on spatial attention resulting from a transient parietal impairment induced by 1-Hz repetitive transcranial magnetic stimulation (rTMS). We examined 50 healthy subjects using the attention network test (ANT) after first applying rTMS to right or left PPC. The right parietal rTMS, but not left PPC rTMS, caused a significant slowing in the mean reaction time (RT) to target presentation following a spatial cue during the ANT test. There were no significant effects of rTMS on mean RT under the no-cue, center-cue, and double-cue conditions, or for each flanker type among the experimental groups. Moreover, after rTMS to the right PPC, test subjects displayed deficits in networks related to alerting and orienting, whereas they exhibited improvement following rTMS to the left PPC. These findings indicate that the right PPC serves an important function in spatial orienting and the alerting activities. We interpreted the enhancement in alerting and spatial orienting function following low-frequency rTMS of left PPC as reflecting a disinhibition of right PPC via an inter-hemispheric inhibition account. PMID- 26869912 TI - Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia. AB - A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive control that involves updating, interference control, and simple maintenance. The current study included a sample of 22 patients with schizophrenia and 20 healthy controls and used a slow event-related fMRI design. We predicted that (1) aberrant salience symptoms would be greater for patient's, (2) patients would demonstrate increased errors during interference control trials, given that patients may be inappropriately assigning salience to distracters, and (3) striatal activity during those errors would be correlated with aberrant salience symptoms. We found a trend toward a significant difference between patients and controls on aberrant salience symptoms, and a significant difference between groups on select task conditions. During interference control trials, patients were more likely to inappropriately encode distracters. For patients, both prefrontal and striatal activity was significantly greater when patients inappropriately identified the distracter as correct compared to activity during distracter rejection. During updating, patient prefrontal and striatal activity was significantly lower for incorrect than correct updating trials. Finally, as predicted, for patients the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the striatal region. These relationships may have implications for treatments that improve cognitive function and reduce symptom expression. PMID- 26869913 TI - Geometry Shapes Propagation: Assessing the Presence and Absence of Cortical Symmetries through a Computational Model of Cortical Spreading Depression. AB - Cortical spreading depression (CSD), a depolarization wave which originates in the visual cortex and travels toward the frontal lobe, has been suggested to be one neural correlate of aura migraine. To the date, little is known about the mechanisms which can trigger or stop aura migraine. Here, to shed some light on this problem and, under the hypothesis that CSD might mediate aura migraine, we aim to study different aspects favoring or disfavoring the propagation of CSD. In particular, by using a computational neuronal model distributed throughout a realistic cortical mesh, we study the role that the geometry has in shaping CSD. Our results are two-fold: first, we found significant differences in the propagation traveling patterns of CSD, both intra and inter-hemispherically, revealing important asymmetries in the propagation profile. Second, we developed methods able to identify brain regions featuring a peculiar behavior during CSD propagation. Our study reveals dynamical aspects of CSD, which, if applied to subject-specific cortical geometry, might shed some light on how to differentiate between healthy subjects and those suffering migraine. PMID- 26869914 TI - Suboptimal Muscle Synergy Activation Patterns Generalize their Motor Function across Postures. AB - We used a musculoskeletal model to investigate the possible biomechanical and neural bases of using consistent muscle synergy patterns to produce functional motor outputs across different biomechanical conditions, which we define as generalizability. Experimental studies in cats demonstrate that the same muscle synergies are used during reactive postural responses at widely varying configurations, producing similarly-oriented endpoint force vectors with respect to the limb axis. However, whether generalizability across postures arises due to similar biomechanical properties or to neural selection of a particular muscle activation pattern has not been explicitly tested. Here, we used a detailed cat hindlimb model to explore the set of feasible muscle activation patterns that produce experimental synergy force vectors at a target posture, and tested their generalizability by applying them to different test postures. We used three methods to select candidate muscle activation patterns: (1) randomly-selected feasible muscle activation patterns, (2) optimal muscle activation patterns minimizing muscle effort at a given posture, and (3) generalizable muscle activation patterns that explicitly minimized deviations from experimentally identified synergy force vectors across all postures. Generalizability was measured by the deviation between the simulated force direction of the candidate muscle activation pattern and the experimental synergy force vectors at the test postures. Force angle deviations were the greatest for the randomly selected feasible muscle activation patterns (e.g., >100 degrees ), intermediate for effort-wise optimal muscle activation patterns (e.g., ~20 degrees ), and smallest for generalizable muscle activation patterns (e.g., <5 degrees ). Generalizable muscle activation patterns were suboptimal in terms of effort, often exceeding 50% of the maximum possible effort (cf. ~5% in minimum-effort muscle activation patterns). The feasible muscle activation ranges of individual muscles associated with producing a specific synergy force vector was reduced by ~45% when generalizability requirements were imposed. Muscles recruited in the generalizable muscle activation patterns had less sensitive torque-producing characteristics to changes in postures. We conclude that generalization of function across postures does not arise from limb biomechanics or a single optimality criterion. Muscle synergies may reflect acquired motor solutions globally tuned for generalizability across biomechanical contexts, facilitating rapid motor adaptation. PMID- 26869917 TI - A Quantitative Study of Network Robustness in Resting-State fMRI in Young and Elder Adults. AB - Brain connectivity analysis has shown great promise in understanding how aging affects functional connectivity; however, an explanatory framework to study healthy aging in terms of network efficiency is still missing. Here, we study network robustness, i.e., resilience to perturbations, in resting-state functional connectivity networks (rs-fMRI) in young and elder subjects. We apply analytic measures of network communication efficiency in the human brain to investigate the compensatory mechanisms elicited in aging. Specifically, we quantify the effect of "lesioning" (node canceling) of either single regions of interest (ROI) or whole networks on global connectivity metrics (i.e., efficiency). We find that young individuals are more resilient than old ones to random "lesioning" of brain areas; global network efficiency is over 3 times lower in older subjects relative to younger subjects. On the other hand, the "lesioning" of central and limbic structures in young subjects yield a larger efficiency loss than in older individuals. Overall, our study shows a more idiosyncratic response to specific brain network "lesioning" in elder compared to young subjects, and that young adults are more resilient to random deletion of single nodes compared to old adults. PMID- 26869915 TI - Pain Related Cortical Oscillations: Methodological Advances and Potential Applications. AB - Alongside the time-locked event-related potentials (ERPs), nociceptive somatosensory inputs can induce modulations of ongoing oscillations, appeared as event-related synchronization or desynchronization (ERS/ERD) in different frequency bands. These ERD/ERS activities are suggested to reflect various aspects of pain perception, including the representation, encoding, assessment, and integration of the nociceptive sensory inputs, as well as behavioral responses to pain, even the precise details of their roles remain unclear. Previous studies investigating the functional relevance of ERD/ERS activities in pain perception were normally done by assessing their latencies, frequencies, magnitudes, and scalp distributions, which would be then correlated with subjective pain perception or stimulus intensity. Nevertheless, these temporal, spectral, and spatial profiles of stimulus induced ERD/ERS could only partly reveal the dynamics of brain oscillatory activities. Indeed, additional parameters, including but not limited to, phase, neural generator, and cross frequency couplings, should be paid attention to comprehensively and systemically evaluate the dynamics of oscillatory activities associated with pain perception and behavior. This would be crucial in exploring the psychophysiological mechanisms of neural oscillation, and in understanding the neural functions of cortical oscillations involved in pain perception and behavior. Notably, some chronic pain (e.g., neurogenic pain and complex regional pain syndrome) patients are often associated with the occurrence of abnormal synchronized oscillatory brain activities, and selectively modulating cortical oscillatory activities has been showed to be a potential therapy strategy to relieve pain with the application of neurostimulation techniques, e.g., repeated transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). Thus, the investigation of the oscillatory activities proceeding from phenomenology to function, opens new perspectives to address questions in human pain psychophysiology and pathophysiology, thereby promoting the establishment of rational therapeutic strategy. PMID- 26869916 TI - Using Make for Reproducible and Parallel Neuroimaging Workflow and Quality Assurance. AB - The contribution of this paper is to describe how we can program neuroimaging workflow using Make, a software development tool designed for describing how to build executables from source files. A makefile (or a file of instructions for Make) consists of a set of rules that create or update target files if they have not been modified since their dependencies were last modified. These rules are processed to create a directed acyclic dependency graph that allows multiple entry points from which to execute the workflow. We show that using Make we can achieve many of the features of more sophisticated neuroimaging pipeline systems, including reproducibility, parallelization, fault tolerance, and quality assurance reports. We suggest that Make permits a large step toward these features with only a modest increase in programming demands over shell scripts. This approach reduces the technical skill and time required to write, debug, and maintain neuroimaging workflows in a dynamic environment, where pipelines are often modified to accommodate new best practices or to study the effect of alternative preprocessing steps, and where the underlying packages change frequently. This paper has a comprehensive accompanying manual with lab practicals and examples (see Supplemental Materials) and all data, scripts, and makefiles necessary to run the practicals and examples are available in the "makepipelines" project at NITRC. PMID- 26869918 TI - Assessing Visuospatial Abilities in Healthy Aging: A Novel Visuomotor Task. AB - This study examined the efficacy of a novel reaching-and-grasping task in determining visuospatial abilities across adulthood. The task required male and female young (18-25 years) and older adults (60-82 years) to replicate a series of complex models by locating and retrieving the appropriate building blocks from an array. The task allows visuospatial complexity to be manipulated independently from the visuomotor demands. Mental rotation and spatial visualization abilities were assessed. The results showed that the time taken to complete the tasks increased with increased mental rotation complexity. Patterns of hand use were also influenced by the complexity of the models being constructed with right hand use being greater for the less complex models. In addition, although older adults consistently performed the visuomotor tasks slower than the younger adults, their performance was comparable when expressed as the percent change in task demands. This is suggestive that spatial abilities are preserved in older adults. Given the ecologically validity, the described task is an excellent candidate for investigating: (1) developmental; (2) sex-based; and (3) pathology-based differences in spatial abilities in the visuomotor domain. PMID- 26869920 TI - Commentary: Possible involvement of lysosomal dysfunction in pathological changes of the brain in aged progranulin-deficient mice. PMID- 26869921 TI - Motor Performance is Impaired Following Vestibular Stimulation in Ageing Mice. AB - Balance and maintaining postural equilibrium are important during stationary and dynamic movements to prevent falls, particularly in older adults. While our sense of balance is influenced by vestibular, proprioceptive, and visual information, this study focuses primarily on the vestibular component and its age-related effects on balance. C57Bl/6J mice of ages 1, 5-6, 8-9 and 27-28 months were tested using a combination of standard (such as grip strength and rotarod) and newly-developed behavioral tests (including balance beam and walking trajectory tests with a vestibular stimulus). In the current study, we confirm a decline in fore-limb grip strength and gross motor coordination as age increases. We also show that a vestibular stimulus of low frequency (2-3 Hz) and duration can lead to age-dependent changes in balance beam performance, which was evident by increases in latency to begin walking on the beam as well as the number of times hind-feet slip (FS) from the beam. Furthermore, aged mice (27-28 months) that received continuous access to a running wheel for 4 weeks did not improve when retested. Mice of ages 1, 10, 13 and 27-28 months were also tested for changes in walking trajectory as a result of the vestibular stimulus. While no linear relationship was observed between the changes in trajectory and age, 1-month-old mice were considerably less affected than mice of ages 10, 13 and 27-28 months. CONCLUSION: this study confirms there are age-related declines in grip strength and gross motor coordination. We also demonstrate age-dependent changes to finer motor abilities as a result of a low frequency and duration vestibular stimulus. These changes showed that while the ability to perform the balance beam task remained intact across all ages tested, behavioral changes in task performance were observed. PMID- 26869922 TI - Aberrant Functional Connectivity and Structural Atrophy in Subcortical Vascular Cognitive Impairment: Relationship with Cognitive Impairments. AB - Abnormal structures in the cortical and subcortical regions have been identified in subcortical vascular cognition impairment (SVCI). However, little is known about the functional alterations in SVCI, and no study refers to the functional connectivity in the prefrontal and subcortical regions in this context. The medial prefrontal cortex (MPFC) is an important region of the executive network and default mode network, and the subcortical thalamus plays vital roles in mediating or modulating these two networks. To investigate both thalamus- and MPFC-related functional connectivity as well as its relationship with cognition in SVCI, 32 SVCI patients and 23 control individuals were administered neuropsychological assessments. They also underwent structural and functional magnetic resonance imaging scans. Voxel-based morphometry and functional connectivity analysis were performed to detect gray matter (GM) atrophy and to characterize the functional alterations in the thalamus and the MPFC. For structural data, we observed that GM atrophy was distributed in both cortical regions and subcortical areas. For functional data, we observed that the thalamus functional connectivity in SVCI was significantly decreased in several cortical regions [i.e., the orbitofrontal lobe (OFL)], which are mainly involved in executive function and memory function. However, connectivity was increased in several frontal regions (i.e., the inferior frontal gyrus), which may be induced by the compensatory recruitment of the decreased functional connectivity. The MPFC functional connectivity was also decreased in executive- and memory-related regions (i.e., the anterior cingulate cortex) along with a motor region (i.e., the supplementary motor area). In addition, the cognitive performance was closely correlated with functional connectivity between the left thalamus and the left OFL in SVCI. The present study, thus, provides evidence for an association between structural and functional alterations, and sheds light on the underlying neural mechanisms of executive dysfunction in SVCI. PMID- 26869919 TI - Molecular Pathways Bridging Frontotemporal Lobar Degeneration and Psychiatric Disorders. AB - The overlap of symptoms between neurodegenerative and psychiatric diseases has been reported. Neuropsychiatric alterations are commonly observed in dementia, especially in the behavioral variant of frontotemporal dementia (bvFTD), which is the most common clinical FTD subtype. At the same time, psychiatric disorders, like schizophrenia (SCZ), can display symptoms of dementia, including features of frontal dysfunction with relative sparing of memory. In the present review, we discuss common molecular features in these pathologies with a special focus on FTD. Molecules like Brain Derived Neurotrophic Factor (BDNF) and progranulin are linked to the pathophysiology of both neurodegenerative and psychiatric diseases. In these brain-associated illnesses, the presence of disease-associated variants in BDNF and progranulin (GRN) genes cause a reduction of circulating proteins levels, through alterations in proteins expression or secretion. For these reasons, we believe that prevention and therapy of psychiatric and neurological disorders could be achieved enhancing both BDNF and progranulin levels thanks to drug discovery efforts. PMID- 26869923 TI - A Humanized Clinically Calibrated Quantitative Systems Pharmacology Model for Hypokinetic Motor Symptoms in Parkinson's Disease. AB - The current treatment of Parkinson's disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very successful, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor cognitive and psychiatric symptoms. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a computer-based Quantitative Systems Pharmacology (QSP) platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R (2) = 0.71) with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations). When incorporating Parkinsonian (PD) pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity) from a dopamine depletion of 70% onward. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R (2) = 0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not for acute treatment in PD. PMID- 26869924 TI - Mechanisms Underlying the Anti-Inflammatory Effects of Clinacanthus nutans Lindau Extracts: Inhibition of Cytokine Production and Toll-Like Receptor-4 Activation. AB - Clinacanthus nutans has had a long history of use in folk medicine in Malaysia and Southeast Asia; mostly in the relief of inflammatory conditions. In this study, we investigated the effects of different extracts of C. nutans upon lipopolysaccharide (LPS) induced inflammation in order to identify its mechanism of action. Extracts of leaves and stem bark of C. nutans were prepared using polar and non-polar solvents to produce four extracts, namely polar leaf extract (LP), non-polar leaf extract (LN), polar stem extract (SP), and non-polar stem extracts (SN). The extracts were standardized by determining its total phenolic and total flavonoid contents. Its anti-inflammatory effects were assessed on LPS induced nitrite release in RAW264.7 macrophages and Toll-like receptor (TLR-4) activation in TLR-4 transfected human embryonic kidney cells (HEK-Blue(TM)-hTLR4 cells). The levels of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1beta, IL 6, IL-12p40, and IL-17) in treated RAW264.7 macrophages were quantified to verify its anti-inflammatory effects. Western blotting was used to investigate the effect of the most potent extract (LP) on TLR-4 related inflammatory proteins (p65, p38, ERK, JNK, IRF3) in RAW264.7 macrophages. All four extracts produced a significant, concentration-dependent reduction in LPS-stimulated nitric oxide, LPS-induced TLR-4 activation in HEK-Blue(TM)-hTLR4 cells and LPS-stimulated cytokines production in RAW264.7 macrophages. The most potent extract, LP, also inhibited all LPS-induced TLR-4 inflammatory proteins. These results provide a basis for understanding the mechanisms underlying the previously demonstrated anti-inflammatory activity of C. nutans extracts. PMID- 26869925 TI - Editorial: Serotonin and Memory. PMID- 26869926 TI - Editorial: 5-HT2A/2B/2C Receptors, Memory, and Neuropsychiatric Disorders. PMID- 26869927 TI - Syndecans as Cell Surface Receptors in Cancer Biology. A Focus on their Interaction with PDZ Domain Proteins. AB - Syndecans are transmembrane receptors with ectodomains that are modified by glycosaminoglycan chains. The ectodomains can interact with a wide variety of molecules, including growth factors, cytokines, proteinases, adhesion receptors, and extracellular matrix (ECM) components. The four syndecans in mammals are expressed in a development-, cell-type-, and tissue-specific manner and can function either as co-receptors with other cell surface receptors or as independent adhesion receptors that mediate cell signaling. They help regulate cell proliferation and migration, angiogenesis, cell/cell and cell/ECM adhesion, and they may participate in several key tumorigenesis processes. In some cancers, syndecan expression regulates tumor cell proliferation, adhesion, motility, and other functions, and may be a prognostic marker for tumor progression and patient survival. The short cytoplasmic tail is likely to be involved in these events through recruitment of signaling partners. In particular, the conserved carboxyl terminal EFYA tetrapeptide sequence that is present in all syndecans binds to some PDZ domain-containing proteins that may function as scaffold proteins that recruit signaling and cytoskeletal proteins to the plasma membrane. There is growing interest in understanding these interactions at both the structural and biological levels, and recent findings show their high degree of complexity. Parameters that influence the recruitment of PDZ domain proteins by syndecans, such as binding specificity and affinity, are the focus of active investigations and are important for understanding regulatory mechanisms. Recent studies show that binding may be affected by post-translational events that influence regulatory mechanisms, such as phosphorylation within the syndecan cytoplasmic tail. PMID- 26869929 TI - Spectrum-Effect Relationships Between Chemical Fingerprints and Antibacterial Effects of Lonicerae Japonicae Flos and Lonicerae Flos Base on UPLC and Microcalorimetry. AB - The traditional Chinese medicines Lonicerae Japonicae Flos (LJF, Jinyinhua in Chinese) and Lonicerae Flos (LF, Shanyinhua in Chinese) refer to the flower buds of five plants belonging to the Caprifoliaceae family. Until 2000, all of these were officially listed as a single item, LJF (Jinyinhua), in the Chinese Pharmacopoeia. However, there have recently been many academic controversies concerning the separation and combination of LJF and LF in administrative regulation. Till now there has been little work completed evaluating the relationships between biological activity and chemical properties among these drugs. Microcalorimetry and UPLC were used along with principal component analysis (PCA), hierarchical cluster analysis (HCA), and canonical correlation analysis (CCA) to investigate the relationships between the chemical ingredients and the antibacterial effects of LJF and LF. Using multivariate statistical analysis, LJF and LF could be initially separated according to their chemical fingerprints, and the antibacterial effects of the two herbal drugs were divided into two clusters. This result supports the disaggregation of LJF and LF by the Pharmacopoeia Committee. However, the sample of Lonicera fulvotomentosa Hsu et S. C. Cheng turned out to be an intermediate species, with similar antibacterial efficacy as LJF. The results of CCA indicated that chlorogenic acid and 3,4 Dicaffeoylquinic acid were the major components generating antibacterial effects. Furthermore, 3,4-Dicaffeoylquinic acid could be used as a new marker ingredient for quality control of LJF and LF. PMID- 26869931 TI - Poly-Cross-Linked PEI Through Aromatically Conjugated Imine Linkages as a New Class of pH-Responsive Nucleic Acids Packing Cationic Polymers. AB - Cationic polyimines polymerized through aromatically conjugated bis-imine linkages and intra-molecular cross-linking were found to be a new class of effective transfection materials for their flexibility in structural optimization, responsiveness to intracellular environment, the ability to facilitate endosome escape and cytosol release of the nucleic acids, as well as self-metabolism. When three phthalaldehydes of different substitution positions were used to polymerize highly branched low-molecular weight polyethylenimine (PEI 1.8K), the product through ortho-phthalimines (named PPOP) showed significantly higher transfection activity than its two tere- and iso-analogs (named PPTP and PPIP). Physicochemical characterization confirmed the similarity of three polyimines in pH-responded degradability, buffer capacity, as well as the size and Zeta potential of the polyplexes formed from the polymers. A mechanistic speculation may be that the ortho-positioned bis-imine linkage of PPOP may only lead to the straight trans-configuration due to steric hindrance, resulting in larger loops of intra-polymer cross-linking and more flexible backbone. PMID- 26869928 TI - Matricryptins Network with Matricellular Receptors at the Surface of Endothelial and Tumor Cells. AB - The extracellular matrix (ECM) is a source of bioactive fragments called matricryptins or matrikines resulting from the proteolytic cleavage of extracellular proteins (e.g., collagens, elastin, and laminins) and proteoglycans (e.g., perlecan). Matrix metalloproteinases (MMPs), cathepsins, and bone morphogenetic protein-1 release fragments, which regulate physiopathological processes including tumor growth, metastasis, and angiogenesis, a pre-requisite for tumor growth. A number of matricryptins, and/or synthetic peptides derived from them, are currently investigated as potential anti-cancer drugs both in vitro and in animal models. Modifications aiming at improving their efficiency and their delivery to their target cells are studied. However, their use as drugs is not straightforward. The biological activities of these fragments are mediated by several receptor families. Several matricryptins may bind to the same matricellular receptor, and a single matricryptin may bind to two different receptors belonging or not to the same family such as integrins and growth factor receptors. Furthermore, some matricryptins interact with each other, integrins and growth factor receptors crosstalk and a signaling pathway may be regulated by several matricryptins. This forms an intricate 3D interaction network at the surface of tumor and endothelial cells, which is tightly associated with other cell-surface associated molecules such as heparan sulfate, caveolin, and nucleolin. Deciphering the molecular mechanisms underlying the behavior of this network is required in order to optimize the development of matricryptins as anti cancer agents. PMID- 26869930 TI - Metabolomics Coupled with Multivariate Data and Pathway Analysis on Potential Biomarkers in Cholestasis and Intervention Effect of Paeonia lactiflora Pall. AB - BACKGROUND: The dried root of Paeonia lactiflora Pall. (PLP) is a classical Chinese herbal medicine that has been used to treat hepatic disease for 1000s of years. Our previous work suggested that PLP can be used to treat hepatitis with severe cholestasis. This study explored the mechanism by which PLP affects ANIT induced cholestasis in rats using a metabolomics approach. METHODS: The effects of PLP on serum indices (TBIL, DBIL, AST, ALT, ALP, and TBA) and the histopathology of the liver were analyzed. Moreover, UHPLC-Q-TOF was performed to identify the possible effect of PLP on metabolites. The pathway analysis was conducted to illustrate the pathways and network by which PLP treats cholestasis. RESULT: High-dose PLP remarkably down-regulated the serum indices and alleviated histological damage to the liver. Metabolomics analyses showed that the therapeutic effect of high-dose PLP is mainly associated with the regulation of several metabolites, such as glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, L(D)-arginine, and L-tryptophan. A pathway analysis showed that the metabolites were related to bile acid secretion and amino acid metabolism. In addition, the significant changes in bile acid transporters also indicated that bile acid metabolism might be involved in the therapeutic effect of PLP on cholestasis. Moreover, a principal component analysis indicated that the metabolites in the high-dose PLP group were closer to those of the control, whereas those of the moderate dose or low-dose PLP group were closer to those of the ANIT group. This finding indicated that metabolites may be responsible for the differences between the effects of low-dose and moderate-dose PLP. CONCLUSION: The therapeutic effect of high-dose PLP on cholestasis is possibly related to regulation of bile acid secretion and amino acid metabolism. Moreover, these findings may help better understand the mechanisms of disease and provide a potential therapy for cholestasis. PMID- 26869932 TI - Mismatch Negativity Affects Muscle Fatigue during Repeated Contraction Trials of Different Durations. AB - We examined the effect of involuntary attention switching (related to mismatch negativity generation in the oddball paradigm) on fatigue development during trials of different durations. The experiment consisted of two trials, long (40 min) and short (15 min), and two experimental conditions in each trial: the simple reaction task (deviants-only paradigm) and the stimuli recognition task (oddball paradigm). In each condition, a participant responded to each target acoustic stimulus by squeezing a handgrip dynamometer. We found the significantly lower rates of fatigue development in the short-trial deviants-only paradigm compared to the long trial. The short- and the long-trial oddball paradigms differed significantly from both the short- and the long-trial deviants-only paradigms. The results demonstrated that the fatigue developed differently depending on the expected trial duration. The involuntary activation of attention broke this subconscious regulative mechanism leading to increase of the compression force during the long trial and its decrease during the short. PMID- 26869933 TI - Strong Ion Regulatory Abilities Enable the Crab Xenograpsus testudinatus to Inhabit Highly Acidified Marine Vent Systems. AB - Hydrothermal vent organisms have evolved physiological adaptations to cope with extreme abiotic conditions including temperature and pH. To date, acid-base regulatory abilities of vent organisms are poorly investigated, although this physiological feature is essential for survival in low pH environments. We report the acid-base regulatory mechanisms of a hydrothermal vent crab, Xenograpsus testudinatus, endemic to highly acidic shallow-water vent habitats with average environment pH-values ranging between 5.4 and 6.6. Within a few hours, X. testudinatus restores extracellular pH (pHe) in response to environmental acidification of pH 6.5 (1.78 kPa pCO2) accompanied by an increase in blood [Formula: see text] levels from 8.8 +/- 0.3 to 31 +/- 6 mM. Branchial Na(+)/K(+) ATPase (NKA) and V-type H(+)-ATPase (VHA), the major ion pumps involved in branchial acid-base regulation, showed dynamic increases in response to acidified conditions on the mRNA, protein and activity level. Immunohistochemical analyses demonstrate the presence of NKA in basolateral membranes, whereas the VHA is predominantly localized in cytoplasmic vesicles of branchial epithelial- and pillar-cells. X. testudinatus is closely related to other strong osmo-regulating brachyurans, which is also reflected in the phylogeny of the NKA. Accordingly, our results suggest that the evolution of strong ion regulatory abilities in brachyuran crabs that allowed the occupation of ecological niches in euryhaline, freshwater, and terrestrial habitats are probably also linked to substantial acid base regulatory abilities. This physiological trait allowed X. testudinatus to successfully inhabit one of the world's most acidic marine environments. PMID- 26869934 TI - Heart Rate and Extracellular Sodium and Potassium Modulation of Gap Junction Mediated Conduction in Guinea Pigs. AB - BACKGROUND: Recent studies suggested that cardiac conduction in murine hearts with narrow perinexi and 50% reduced connexin43 (Cx43) expression is more sensitive to relatively physiological changes of extracellular potassium ([K(+)]o) and sodium ([Na(+)]o). PURPOSE: Determine whether similar [K(+)]o and [Na(+)]o changes alter conduction velocity (CV) sensitivity to pharmacologic gap junction (GJ) uncoupling in guinea pigs. METHODS: [K(+)]o and [Na(+)]o were varied in Langendorff perfused guinea pig ventricles (Solution A: [K(+)]o = 4.56 and [Na(+)]o = 153.3 mM. Solution B: [K(+)]o = 6.95 and [Na(+)]o = 145.5 mM). Gap junctions were inhibited with carbenoxolone (CBX) (15 and 30 MUM). Epicardial CV was quantified by optical mapping. Perinexal width was measured with transmission electron microscopy. Total and phosphorylated Cx43 were evaluated by western blotting. RESULTS: Solution composition did not alter CV under control conditions or with 15MUM CBX. Decreasing the basic cycle length (BCL) of pacing from 300 to 160 ms decreased CV uniformly with both solutions. At 30 MUM CBX, a change in solution did not alter CV either longitudinally or transversely at BCL = 300 ms. However, reducing BCL to 160 ms caused CV to decrease more in hearts perfused with Solution B than A. Solution composition did not alter perinexal width, nor did it change total or phosphorylated serine 368 Cx43 expression. These data suggest that the solution dependent CV changes were independent of altered perinexal width or GJ coupling. Action potential duration was always shorter in hearts perfused with Solution B than A, independent of pacing rate and/or CBX concentration. CONCLUSIONS: Increased heart rate and GJ uncoupling can unmask small CV differences caused by changing [K(+)]o and [Na(+)]o. These data suggest that modulating extracellular ionic composition may be a novel anti-arrhythmic target in diseases with abnormal GJ coupling, particularly when heart rate cannot be controlled. PMID- 26869936 TI - Benefits of Group Living Include Increased Feeding Efficiency and Lower Mass Loss during Desiccation in the Social and Inbreeding Spider Stegodyphus dumicola. AB - Group living carries a price: it inherently entails increased competition for resources and reproduction, and may also be associated with mating among relatives, which carries costs of inbreeding. Nonetheless, group living and sociality is found in many animals, and understanding the direct and indirect benefits of cooperation that override the inherent costs remains a challenge in evolutionary ecology. Individuals in groups may benefit from more efficient management of energy or water reserves, for example in the form of reduced water or heat loss from groups of animals huddling, or through reduced energy demands afforded by shared participation in tasks. We investigated the putative benefits of group living in the permanently social spider Stegodyphus dumicola by comparing the effect of group size on standard metabolic rate, lipid/protein content as a body condition measure, feeding efficiency, per capita web investment, and weight/water loss and survival during desiccation. Because energetic expenditure is temperature sensitive, some assays were performed under varying temperature conditions. We found that feeding efficiency increased with group size, and the rate of weight loss was higher in solitary individuals than in animals in groups of various sizes during desiccation. Interestingly, this was not translated into differences in survival or in standard metabolic rate. We did not detect any group size effects for other parameters, and group size effects did not co-vary with experimental temperature in a predictive manner. Both feeding efficiency and mass loss during desiccation are relevant ecological factors as the former results in lowered predator exposure time, and the latter benefits social spiders which occupy arid, hot environments. PMID- 26869935 TI - The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts. AB - Chronic liver injury, resulted from different etiologies (e.g., virus infection, alcohol abuse, nonalcoholic steatohepatitis (NASH) and cholestasis) can lead to liver fibrosis characterized by the excess accumulation of extracellular matrix (ECM) proteins (e.g., type I collagen). Hepatic myofibroblasts that are activated upon liver injury are the key producers of ECM proteins, contributing to both the initiation and progression of liver fibrosis. Hepatic stellate cells (HSCs) and to a lesser extent, portal fibroblast, are believed to be the precursor cells that give rise to hepatic myofibroblasts in response to liver injury. Although, much progress has been made toward dissecting the lineage origin of myofibroblasts, how these cells are activated and become functional producers of ECM proteins remains incompletely understood. Activation of myofibroblasts is a complex process that involves the interactions between parenchymal and non parenchymal cells, which drives the phenotypic change of HSCs from a quiescent stage to a myofibroblastic and active phenotype. Accumulating evidence has suggested a critical role of NADPH oxidase (NOX), a multi-component complex that catalyzes reactions from molecular oxygen to reactive oxygen species (ROS), in the activation process of hepatic myofibroblasts. NOX isoforms, including NOX1, NOX2 and NOX4, and NOX-derived ROS, have all been implicated to regulate HSC activation and hepatocyte apoptosis, both of which are essential steps for initiating liver fibrosis. This review highlights the importance of NOX isoforms in hepatic myofibroblast activation and the progression of liver fibrosis, and also discusses the therapeutic potential of targeting NOXs for liver fibrosis and associated hepatic diseases. PMID- 26869938 TI - Coordinated Development of Muscles and Tendon-Like Structures: Early Interactions in the Drosophila Leg. AB - The formation of the musculoskeletal system is a remarkable example of tissue assembly. In both vertebrates and invertebrates, precise connectivity between muscles and skeleton (or exoskeleton) via tendons or equivalent structures is fundamental for movement and stability of the body. The molecular and cellular processes underpinning muscle formation are well-established and significant advances have been made in understanding tendon development. However, the mechanisms contributing to proper connection between these two tissues have received less attention. Observations of coordinated development of tendons and muscles suggest these tissues may interact during the different steps in their development. There is growing evidence that, depending on animal model and muscle type, these interactions can take place from progenitor induction to the final step of the formation of the musculoskeletal system. Here, we briefly review and compare the mechanisms behind muscle and tendon interaction throughout the development of vertebrates and Drosophila before going on to discuss our recent findings on the coordinated development of muscles and tendon-like structures in Drosophila leg. By altering apodeme formation (the functional Drosophila equivalent of tendons in vertebrates) during the early steps of leg development, we affect the spatial localization of subsequent myoblasts. These findings provide the first evidence of the developmental impact of early interactions between muscle and tendon-like precursors, and confirm the appendicular Drosophila muscle system as a valuable model for studying these processes. PMID- 26869937 TI - Targeting MicroRNA Function in Respiratory Diseases: Mini-Review. AB - MicroRNAs (miRNAs) are small non-coding RNA molecules that modulate expression of the majority of genes by inhibiting protein translation. Growing literature has identified functional roles for miRNAs across a broad range of biological processes. As such, miRNAs are recognized as potential disease biomarkers and novel targets for therapies. While several miRNA-targeted therapies are currently in clinical trials (e.g., for the treatment of hepatitis C virus infection and cancer), no therapies have targeted miRNAs in respiratory diseases in the clinic. In this mini-review, we review the current knowledge on miRNA expression and function in respiratory diseases, intervention strategies to target miRNA function, and considerations specific to respiratory diseases. Altered miRNA expression profiles have been reported in a number of respiratory diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis. These include alterations in isolated lung tissue, as well as sputum, bronchoalveolar lavage fluids and peripheral blood or serum. The observed alterations in easily accessible body fluids (e.g., serum) have been proposed as new biomarkers that may inform disease diagnosis and patient management. In a subset of studies, miRNA-targeted interventions also improved disease outcomes, indicating functional roles for altered miRNA expression in disease pathogenesis. In fact, direct administration of miRNA-targeting molecules to the lung has yielded promising results in a number of animal models. The ability to directly administer compounds to the lung holds considerable promise and may limit potential off-target effects and side effects caused by the systemic administration required to treat other diseases. PMID- 26869940 TI - Utility of a Novel Biofeedback Device for Within-Breath Modulation of Heart Rate in Rats: A Quantitative Comparison of Vagus Nerve vs. Right Atrial Pacing. AB - In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA. PMID- 26869939 TI - Mechanical Signaling in the Pathophysiology of Critical Illness Myopathy. AB - The complete loss of mechanical stimuli of skeletal muscles, i.e., the loss of external strain, related to weight bearing, and internal strain, related to the contraction of muscle cells, is uniquely observed in pharmacologically paralyzed or deeply sedated mechanically ventilated intensive care unit (ICU) patients. The preferential loss of myosin and myosin associated proteins in limb and trunk muscles is a significant characteristic of critical illness myopathy (CIM) which separates CIM from other types of acquired muscle weaknesses in ICU patients. Mechanical silencing is an important factor triggering CIM. Microgravity or ground based microgravity models form the basis of research on the effect of muscle unloading-reloading, but the mechanisms and effects may differ from the ICU conditions. In order to understand how mechanical tension regulates muscle mass, it is critical to know how muscles sense mechanical information and convert stimulus to intracellular biochemical actions and changes in gene expression, a process called cellular mechanotransduction. In adult skeletal muscles and muscle fibers, this process may differ, the same stimulus can cause divergent response and the same fiber type may undergo opposite changes in different muscles. Skeletal muscle contains multiple types of mechano-sensors and numerous structures that can be affected differently and hence respond differently in distinct muscles. PMID- 26869941 TI - The Addictive Model of Self-Harming (Non-suicidal and Suicidal) Behavior. AB - INTRODUCTION: Behavioral addictions such as gambling, sun-tanning, shopping, Internet use, work, exercise, or even love and sex are frequent, and share many characteristics and common neurobiological and genetic underpinnings with substance addictions (i.e., tolerance, withdrawal, and relapse). Recent literature suggests that both non-suicidal self-injury (NSSI) and suicidal behavior (SB) can also be conceptualized as addictions. The major aim of this mini review is to review the literature and explore the neurobiological and psychological mechanisms underlying the addiction to self-harming behaviors. METHOD: This is a narrative review. The authors performed literature searches in PubMed and Google for suicidal behavior, self-harming, addiction, and "major repeaters." Given the scarce literature on the topic, a subset of the most closely related studies was selected. The authors also focused on three empirical studies testing the hypothesis that major repeaters (individuals with >=5 lifetime suicide attempts) represent a distinctive suicidal phenotype and are the individuals at risk of developing an addiction to SB. RESULTS: The authors reviewed the concept of behavioral addictions and major repeaters, current empirical evidence testing concerning whether or not NSSI and SB can be understood as "addictions," and the putative mechanisms underlying them. CONCLUSION: Our review suggests that both NSSI and SB can be conceptualized as addictions. This is relevant because if some individual's self-harming behaviors are better conceptualized as an addiction, treatment approaches could be tailored to this addiction. PMID- 26869942 TI - "Cognitus & Moi": A Computer-Based Cognitive Remediation Program for Children with Intellectual Disability. AB - Attentional, visuospatial, and social cognition deficits have a negative impact on children's adaptative and social competences and, as a result, on their ability to achieve a normal functioning and behavior. Until now and despite the frequency of those deficits, there is a lack of children's specific cognitive remediation tools specifically dedicated to attentional and visuospatial areas. The "Cognitus & Moi" program involves a variety of exercises in a paper and/or pencil (n = 30) or a computerized format (n = 29) and a strategy coaching approach. Each module of "Cognitus & Moi" targets a single impaired cognitive area, within the limits of cognitive domains' overlapping. The little cartoon character named Cognitus, who illustrates the program, is supposed to be very friendly and kind toward children. Cognitus will accompany them throughout the program for an effective and positive reinforcement. The main goal of "Cognitus & Moi" is to adjust to children's difficulties in daily life. Moreover, since the cognitive remediation benefit is complex to apply in daily life, the program is based on a metacognitive strategy. After a complete neuropsychological assessment and a psychoeducational session (with the child and the parents), 16 1-h-sessions of cognitive remediation with the therapist are proposed. Each session is composed of three parts: (1) computerized tasks focusing on specific attentional or visuospatial components (20 min). The attentional module targets hearing, visual, and divided attention. A double attention task is also proposed. The visuospatial module targets eye tracking and gaze direction, spatial orientation, visuospatial memory and construction, and mental imagery; (2) pen and paper tasks focusing on the same processes (20 min) and a facial emotion recognition task; (3) a proposal of a home-based task (during 20 min). Weekly, specific attentional and visuospatial home tasks are proposed to the child and analyzed with the parents and the therapist. Indeed, home exercises are useful to promote the transfer of strategies to daily life and their subsequent automation. The heterogeneity of cognitive deficits in intellectual deficiency necessitates an individualized cognitive remediation therapy. In this regard, "Cognitus & Moi" seems to be a promising tool. PMID- 26869943 TI - The Richness of Inner Experience: Relating Styles of Daydreaming to Creative Processes. AB - Psychologists have long hypothesized that daydreaming (i.e., engaging in stimulus independent, task-unrelated thoughts and images) may facilitate creativity, but evidence for this hypothesis has been mixed. We propose that, to fully understand the relationship between daydreaming and creativity, it is essential to distinguish between different creative processes as well as between alternative styles of daydreaming. A prominent distinction in creativity research is that between analytic problem solving, which involves incremental and largely conscious processes, and insight, which is characterized by the spontaneity with which an idea springs to mind. In this aspect, insight resembles daydreaming. Indeed, recent evidence has linked daydreaming to creative performance. But like creativity, daydreaming is a multifaceted concept. Daydreams vary in style and content, a fact that is receiving little attention in contemporary research. Not all kinds of daydreaming are likely to have the same effects on creativity. We discuss different factors prevalent in people's daydreaming, such as mood, attentional focus, and intentionality, and consider how these factors may be related to creative processes. We further discuss implications for ways to enhance creativity through deliberate daydreaming practice. PMID- 26869944 TI - Auditory Perceptual Learning in Adults with and without Age-Related Hearing Loss. AB - Introduction : Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL). Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL. Methods : Fifty-six listeners (60-72 y/o), 35 participants with ARHL, and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed training, and no-training group). Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1) Speech-in-noise, (2) time compressed speech, and (3) competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results : Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions : ARHL did not preclude auditory perceptual learning but there was little generalization to untrained conditions. We suggest that most training-related changes occurred at higher level task-specific cognitive processes in both groups. However, these were enhanced by high quality perceptual representations in the normal-hearing group. In contrast, some training-related changes have also occurred at the level of phonemic representations in the ARHL group, consistent with an interaction between bottom-up and top-down processes. PMID- 26869945 TI - Multiple Grammars and the Logic of Learnability in Second Language Acquisition. AB - The core notion of modern Universal Grammar is that language ability requires abstract representation in terms of hierarchy, movement operations, abstract features on words, and fixed mapping to meaning. These mental structures are a step toward integrating representational knowledge of all kinds into a larger model of cognitive psychology. Examining first and second language at once provides clues as to how abstractly we should represent this knowledge. The abstract nature of grammar allows both the formulation of many grammars and the possibility that a rule of one grammar could apply to another grammar. We argue that every language contains Multiple Grammars which may reflect different language families. We develop numerous examples of how the same abstract rules can apply in various languages and develop a theory of how language modules (case marking, topicalization, and quantification) interact to predict L2 acquisition paths. In particular we show in depth how Germanic Verb-second operations, based on Verb-final structure, can apply in English. The argument is built around how and where V2 from German can apply in English, seeking to explain the crucial contrast: "nothing" yelled out Bill/(*)"nothing" yelled Bill out in terms of the necessary abstractness of the V2 rule. PMID- 26869947 TI - Can Gender-Fair Language Reduce Gender Stereotyping and Discrimination? AB - Gender-fair language (GFL) aims at reducing gender stereotyping and discrimination. Two principle strategies have been employed to make languages gender-fair and to treat women and men symmetrically: neutralization and feminization. Neutralization is achieved, for example, by replacing male masculine forms (policeman) with gender-unmarked forms (police officer), whereas feminization relies on the use of feminine forms to make female referents visible (i.e., the applicant... he or she instead of the applicant... he). By integrating research on (1) language structures, (2) language policies, and (3) individual language behavior, we provide a critical review of how GFL contributes to the reduction of gender stereotyping and discrimination. Our review provides a basis for future research and for scientifically based policy-making. PMID- 26869948 TI - How to Set Focal Categories for Brief Implicit Association Test? "Good" Is Good, "Bad" Is Not So Good. AB - Three studies were conducted to examine the validity of the four versions of BIATs that are supposed to measure the same construct but differ in shared focal category. Study 1 investigated the criterion validity of four BIATs measuring attitudes toward flower versus insect. Study 2 examined the experimental sensitivity of four BIATs by considering attitudes toward induced ingroup versus outgroup. Study 3 examined the predictive power of the four BIATs by investigating attitudes toward the commercial beverages Coke versus Sprite. The findings suggested that for the two attributes "good" and "bad," "good" rather than "bad" proved to be good as a shared focal category; for two targets, so long as they clearly differed in goodness or valence, the "good" rather than "bad" target emerged as good for a shared focal category. Beyond this case, either target worked well. These findings may facilitate the understanding of the BIAT and its future applications. PMID- 26869946 TI - What Is Specific and What Is Shared Between Numbers and Words? AB - Reading and spelling performance have a significant correlation with number transcoding, which is the ability to establish a relationship between the verbal and Arabic representations of numbers, when a conversion of numerical symbols from one notation to the other is necessary. The aim of the present study is to reveal shared and non-shared mechanisms involved in reading and writing of words and Arabic numerals in Brazilian school-aged children. One hundred and seventy two children from second to fourth grades were evaluated. All of them had normal intelligence. We conducted a series of hierarchical regression models using scores on word spelling and reading single words and Arabic numerals, as dependent variables. As predictor variables we investigated intelligence, the phonological and visuospatial components of working memory (WM) and phonemic awareness. All of the writing and reading tasks (single word spelling and reading as well as number reading and number writing) were significantly correlated to each other. In the regression models, phonological WM was specifically associated to word reading. Phonemic awareness was the only cognitive variable that systematically predicted all of the school skills investigated, both numerical and word tasks. This suggests that phonemic awareness is a modular cognitive ability shared by several school tasks and might be an important factor associated to the comorbidity between dyslexia and dyscalculia. PMID- 26869949 TI - Modulation of Recognition Memory for Emotional Images by Vertical Vection. AB - Our previous research showed that vertical vection could modulate human mood. We further examined this possibility by using memory recognition task of positive, negative and neutral emotional images with high and low arousal levels. Those images were remembered accidentally while the participants did visual dummy task, and later presented together with novel images during vertical vection-inducing or neutral visual stimuli. The results showed that downward vection facilitated the recognition of negative images and inhibited the recognition of positive ones. These modulations of incidental memory task provide an additional evidence for vection influence on cognitive and emotional processing, and also provide a new paradigm that can be used in future vection and embodied cognition research. PMID- 26869952 TI - The Development of Reference Realization and Narrative in an Australian Contact Language, Wumpurrarni English. AB - The development of narrative skill has been investigated extensively in a wide range of languages, cross-linguistically and in multilingual settings (Berman and Slobin, 1994b; Severing and Verhoeven, 2001; Hickmann, 2004; Stromqvist and Verhoeven, 2004). The present study investigates the development of reference realization in narrative among Indigenous children in a remote urban township in Central Australia. The children, aged between 5 and 14 years, are speakers of a contact language, Wumpurrarni English. Language development is rarely investigated among speakers of minority languages, whose language development is often appraised in the majority language, with little attention to language performance in the speaker's home variety. The present study addresses this gap through a fine-grained qualitative analysis of the development of reference in narrative, drawing on a complex stimulus and a model of discourse strategy. The results show (a) a developmental trajectory similar to that found in other languages, with children aged eight and under producing simpler and less globally organized narratives than older speaker groups, and (b) vulnerability to the changing demands of the stimulus among these younger speakers. In addition, a subset of narrations were produced in "school variety," a style more like Standard Australian English. The results for this set showed that the narrative content and global organization of the productions by 10- and 12-year-olds were more similar to the productions of younger children, than like-aged speakers, who narrated in their home variety. Analysis of speaker responses to two factors of complexity, the stimulus and code choice, illuminated mechanisms for discourse production and development, and suggest that constructing discourse requires co ordination of an underlying schema and on-line construction of a particular story, through the deployment of linguistic devices in a particular narrative context. The analysis showed that these two skills are tightly interdependent, and indeed co-constructing. PMID- 26869951 TI - Mathematics Anxiety, Working Memory, and Mathematics Performance in Secondary School Children. AB - Mathematics anxiety (MA) has been defined as "a feeling of tension and anxiety that interferes with the manipulation of numbers and the solving of math problems in a wide variety of ordinary life and academic situations." Previous studies have suggested that a notable proportion of children in primary and secondary school suffer from MA, which is negatively correlated with calculation skills. The processing efficiency and attentional control theories suggest that working memory (WM) also plays an important part in such anxious feelings. The present study aimed to analyze the academic achievement and cognitive profiles of students with high math anxiety (HMA) and low math anxiety (LMA). Specifically, 32 students with HMA and 34 with LMA matched for age, gender, generalized anxiety, and vocabulary attending sixth to eighth grades were selected from a larger sample. The two groups were tested on reading decoding, reading comprehension, mathematics achievement, and on verbal short-term memory and WM. Our findings showed that HMA students were weak in several measures of mathematics achievement, but not in reading and writing skills, and that students with HMA reported lower scores on short-term memory and WM performances (with associated difficulties in inhibiting irrelevant information) than children with LMA. In addition, a logistic regression showed that weaknesses in inhibitory control and fact retrieval were the strongest variables for classifying children as having HMA or LMA. PMID- 26869950 TI - Fusiform Gyrus Dysfunction is Associated with Perceptual Processing Efficiency to Emotional Faces in Adolescent Depression: A Model-Based Approach. AB - While the extant literature has focused on major depressive disorder (MDD) as being characterized by abnormalities in processing affective stimuli (e.g., facial expressions), little is known regarding which specific aspects of cognition influence the evaluation of affective stimuli, and what are the underlying neural correlates. To investigate these issues, we assessed 26 adolescents diagnosed with MDD and 37 well-matched healthy controls (HCL) who completed an emotion identification task of dynamically morphing faces during functional magnetic resonance imaging (fMRI). We analyzed the behavioral data using a sequential sampling model of response time (RT) commonly used to elucidate aspects of cognition in binary perceptual decision making tasks: the Linear Ballistic Accumulator (LBA) model. Using a hierarchical Bayesian estimation method, we obtained group-level and individual-level estimates of LBA parameters on the facial emotion identification task. While the MDD and HCL groups did not differ in mean RT, accuracy, or group-level estimates of perceptual processing efficiency (i.e., drift rate parameter of the LBA), the MDD group showed significantly reduced responses in left fusiform gyrus compared to the HCL group during the facial emotion identification task. Furthermore, within the MDD group, fMRI signal in the left fusiform gyrus during affective face processing was significantly associated with greater individual-level estimates of perceptual processing efficiency. Our results therefore suggest that affective processing biases in adolescents with MDD are characterized by greater perceptual processing efficiency of affective visual information in sensory brain regions responsible for the early processing of visual information. The theoretical, methodological, and clinical implications of our results are discussed. PMID- 26869954 TI - Structural Priming and Frequency Effects Interact in Chinese Sentence Comprehension. AB - Previous research in several European languages has shown that the language processing system is sensitive to both structural frequency and structural priming effects. However, it is currently not clear whether these two types of effects interact during online sentence comprehension, especially for languages that do not have morphological markings. To explore this issue, the present study investigated the possible interplay between structural priming and frequency effects for sentences containing the Chinese ambiguous construction V NP1 de NP2 in a self-paced reading experiment. The sentences were disambiguated to either the more frequent/preferred NP structure or the less frequent VP structure. Each target sentence was preceded by a prime sentence of three possible types: NP primes, VP primes, and neutral primes. When the ambiguous construction V NP1 de NP2 was disambiguated to the dispreferred VP structure, participants experienced more processing difficulty following an NP prime relative to following a VP prime or a neutral baseline. When the ambiguity was resolved to the preferred NP structure, prime type had no effect. These results suggest that structural priming in comprehension is modulated by the baseline frequency of alternative structures, with the less frequent structure being more subject to structural priming effects. These results are discussed in the context of the error-based, implicit learning account of structural priming. PMID- 26869955 TI - Why are Some Games More Addictive than Others: The Effects of Timing and Payoff on Perseverance in a Slot Machine Game. AB - Manipulating different behavioral characteristics of gambling games can potentially affect the extent to which individuals persevere at gambling, and their transition to problematic behaviors. This has potential impact for mobile gambling technologies and responsible gambling interventions. Two laboratory models pertinent to this are the partial reinforcement extinction effect (PREE) and the trial spacing effect. Both of these might speed up or delay the acquisition and extinction of conditioned behavior. We report an experiment that manipulated the rate of reinforcement and inter trial interval (ITI) on a simulated slot machine where participants were given the choice between gambling and skipping on each trial, before perseverative gambling was measured in extinction, followed by measurements of the illusion of control, depression and impulsivity. We hypothesized that longer ITI's in conjunction with the low rates of reinforcement observed in gambling would lead to greater perseverance. We further hypothesized, given that timing is known to be important in displaying illusory control and potentially in persevering in gambling, that prior exposure to longer intervals might affect illusions of control. An interaction between ITI and rate of reinforcement was observed, as low reinforced gamblers with a long ITI gambled for longer. Respondents also displayed extinction and a PREE. Gamblers exposed to a higher rate of reinforcement gambled for longer in acquisition. Impulsivity was associated with extended perseverance in extinction, and more depressed gamblers in the high reinforcement short ITI group persevered for longer. Performance in the contingency judgment failed to support the second hypothesis: the only significant contrast observed was that participants became better calibrated as the task progressed. PMID- 26869953 TI - Temporal Attention as a Scaffold for Language Development. AB - Language is one of the most fascinating abilities that humans possess. Infants demonstrate an amazing repertoire of linguistic abilities from very early on and reach an adult-like form incredibly fast. However, language is not acquired all at once but in an incremental fashion. In this article we propose that the attentional system may be one of the sources for this developmental trajectory in language acquisition. At birth, infants are endowed with an attentional system fully driven by salient stimuli in their environment, such as prosodic information (e.g., rhythm or pitch). Early stages of language acquisition could benefit from this readily available, stimulus-driven attention to simplify the complex speech input and allow word segmentation. At later stages of development, infants are progressively able to selectively attend to specific elements while disregarding others. This attentional ability could allow them to learn distant non-adjacent rules needed for morphosyntactic acquisition. Because non-adjacent dependencies occur at distant moments in time, learning these dependencies may require correctly orienting attention in the temporal domain. Here, we gather evidence uncovering the intimate relationship between the development of attention and language. We aim to provide a novel approach to human development, bridging together temporal attention and language acquisition. PMID- 26869956 TI - Working Memory Training and CBT Reduces Anxiety Symptoms and Attentional Biases to Threat: A Preliminary Study. AB - Research indicates that cognitive processes linked to the detection of threat stimuli are associated with poor attentional control, placing children and adolescents at increased risk for the development of anxious affect. The current study aimed to provide preliminary data to assess whether an intervention designed to improve attentional control (via working memory; WM) would lead to better performance in tests of WM and would be associated with positive changes in symptoms of trait and test anxiety, increased inhibitory control and reduced attention to threat. Forty adolescents aged 11-14 years who reported elevated anxiety and low attentional control were randomly allocated to a WM training or an active cognitive behavioural therapy (CBT) control group. Post intervention, WM training was associated with greater improvements (versus. CBT) in trained WM tasks. Both groups, however, reported fewer anxiety symptoms, demonstrated increased inhibitory control and a reduction in attentional biases to threat post intervention and these results were maintained at follow up. The study provides indicative evidence which suggests that WM training has similar benefits to a more traditional CBT intervention on reduced anxiety and attentional biases for threat. Future research should aim to replicate the findings in a large sample size and explore the broader impact of training on day-to-day functioning. In addition, further research is needed to identify which participants benefit most from different interventions (using baseline characteristics) on treatment compliance and outcome. PMID- 26869957 TI - An Inner Barrier to Career Development: Preconditions of the Impostor Phenomenon and Consequences for Career Development. AB - The impostor phenomenon (IP) is increasingly recognized as an important psychological construct for career development, yet empirical research on how it functions in this domain is sparse. We investigated in what way impostor feelings are related to the fear of failure, fear of success, self-esteem, and the career development aspects career planning, career striving, and the motivation to lead. We conducted two studies with independent samples of university students (N = 212) in a laboratory study and working professionals (N = 110) in an online study. In both samples, impostor feelings were fostered by fear of failure, fear of success, and low self-esteem and they decreased career planning, career striving, and the motivation to lead. A path analysis showed that impostor feelings had the most negative effects on career planning and career striving in students and on the motivation to lead in working professionals. The results suggest that the IP is relevant to career development in different ways at different career stages. Practical implications and interventions to reduce the negative effects of impostor feelings on career development are discussed. PMID- 26869958 TI - The Asymmetry Bias in Me, We-Others Distance Ratings. The Role of Social Stereotypes. PMID- 26869959 TI - Differential Gaze Patterns on Eyes and Mouth During Audiovisual Speech Segmentation. AB - Speech is inextricably multisensory: both auditory and visual components provide critical information for all aspects of speech processing, including speech segmentation, the visual components of which have been the target of a growing number of studies. In particular, a recent study (Mitchel and Weiss, 2014) established that adults can utilize facial cues (i.e., visual prosody) to identify word boundaries in fluent speech. The current study expanded upon these results, using an eye tracker to identify highly attended facial features of the audiovisual display used in Mitchel and Weiss (2014). Subjects spent the most time watching the eyes and mouth. A significant trend in gaze durations was found with the longest gaze duration on the mouth, followed by the eyes and then the nose. In addition, eye-gaze patterns changed across familiarization as subjects learned the word boundaries, showing decreased attention to the mouth in later blocks while attention on other facial features remained consistent. These findings highlight the importance of the visual component of speech processing and suggest that the mouth may play a critical role in visual speech segmentation. PMID- 26869960 TI - Fluency Expresses Implicit Knowledge of Tonal Symmetry. AB - The purposes of the present study were twofold. First, we sought to establish whether tonal symmetry produces processing fluency. Second, we sought to explore whether symmetry and chunk strength express themselves differently in fluency, as an indication of different mechanisms being involved for sub- and supra-finite state processing. Across two experiments, participants were asked to listen to and memorize artificial poetry showing a mirror symmetry (an inversion, i.e., a type of cross serial dependency); after this training phase, people completed a four-choice RT task in which they were presented with new artificial poetry. Participants were required to identify the stimulus displayed. We found that symmetry sped up responding to the second half of strings, indicating a fluency effect. Furthermore, there was a dissociation between fluency effects arising from symmetry vs. chunk strength, with stronger fluency effects for symmetry rather than chunks in the second half of strings. Taken together, we conjecture a divide between finite state and supra-finite state mechanisms in learning grammatical sequences. PMID- 26869962 TI - Commentary: Does Cognitive Behavior Therapy for psychosis (CBTp) show a sustainable effect on delusions? A meta-analysis. PMID- 26869961 TI - Executive Functions and the Improvement of Thinking Abilities: The Intervention in Reading Comprehension. AB - In this paper, we propose a preliminary theory of executive functions that address in a specific way their relationship with working memory (WM) and higher level cognition. It includes: (a) four core on-line WM executive functions that are involved in every novel and complex cognitive task; (b) two higher order off line executive functions, planning and revision, that are required to resolving the most complex intellectual abilities; and (c) emotional control that is involved in any complex, novel and difficult task. The main assumption is that efficiency on thinking abilities may be improved by specific instruction or training on the executive functions necessary to solving novel and complex tasks involved in these abilities. Evidence for the impact of our training proposal on WM's executive functions involved in higher-level cognitive abilities comes from three studies applying an adaptive program designed to improve reading comprehension in primary school students by boosting the core WM's executive functions involved in it: focusing on relevant information, switching (or shifting) between representations or tasks, connecting incoming information from text with long-term representations, updating of the semantic representation of the text in WM, and inhibition of irrelevant information. The results are consistent with the assumption that cognitive enhancements from the training intervention may have affected not only a specific but also a more domain-general mechanism involved in various executive functions. We discuss some methodological issues in the studies of effects of WM training on reading comprehension. The perspectives and limitations of our approach are finally discussed. PMID- 26869963 TI - "Food Addiction" in Patients with Eating Disorders is Associated with Negative Urgency and Difficulties to Focus on Long-Term Goals. AB - OBJECTIVES: The present study aimed to investigate if eating disorder patients differ in specific personality traits depending on a positive screening of food addiction (FA) and to find a model to predict FA in eating disorder patients using measures of personality and impulsivity. METHODS: Two hundred seventy eight patients, having an eating disorder, self-reported on FA, impulsivity, personality, eating and general psychopathology. Patients were then split into two groups, depending on a positive or negative result on the FA screening. Analysis of variance was used to compare means between the two groups. Stepwise binary logistic regression was used to obtain a predictive model for the presence of FA. RESULTS: Patients with FA had lower self-directedness, and more negative urgency and lack of perseverance than patients not reporting addictive eating. The probability of FA can be predicted by high negative urgency, high reward dependence, and low lack of premeditation. CONCLUSION: Eating disorder patients who have more problems to pursue tasks to the end and to focus on long-term goals seem to be more likely to develop addictive eating patterns. PMID- 26869965 TI - Two Polarities of Attention in Social Contexts: From Attending-to-Others to Attending-to-Self. AB - Social attention is one special form of attention that involves the allocation of limited processing resources in a social context. Previous studies on social attention often regard how attention is directed toward socially relevant stimuli such as faces and gaze directions of other individuals. In contrast to attending to-others, a different line of researches has shown that self-related information such as own face and name automatically captures attention and is preferentially processed comparing to other-related information. These contrasting behavioral effects between attending-to-others and attending-to-self prompt me to consider a synthetic viewpoint for understanding social attention. I propose that social attention operates at two polarizing states: In one extreme, individual tends to attend to the self and prioritize self-related information over others', and, in the other extreme, attention is allocated to other individuals to infer their intentions and desires. Attending-to-self and attending-to-others mark the two ends of an otherwise continuum spectrum of social attention. For a given behavioral context, the mechanisms underlying these two polarities will interact and compete with each other in order to determine a saliency map of social attention that guides our behaviors. An imbalanced competition between these two behavioral and cognitive processes will cause cognitive disorders and neurological symptoms such as autism spectrum disorders and Williams syndrome. I have reviewed both behavioral and neural evidence that support the notion of polarized social attention, and have suggested several testable predictions to corroborate this integrative theory for understanding social attention. PMID- 26869964 TI - The Development of Musical Skills of Underprivileged Children Over the Course of 1 Year: A Study in the Context of an El Sistema-Inspired Program. AB - Developmental research in music has typically centered on the study of single musical skills (e.g., singing, listening) and has been conducted with middle class children who learn music in schools and conservatories. Information on the musical development of children from different social strata, who are enrolled in community-based music programs, remains elusive. This study examined the development of musical skills in underprivileged children who were attending an El Sistema-inspired program in Los Angeles. We investigated how children, predominantly of Latino ethnicity, developed musically with respect to the following musical skills - pitch and rhythmic discrimination, pitch matching, singing a song from memory, and rhythmic entrainment - over the course of 1 year. Results suggested that participation in an El Sistema-inspired program affects children's musical development in distinct ways; with pitch perception and production skills developing faster than rhythmic skills. Furthermore, children from the same ethnic and social background, who did not participate in the El Sistema-inspired music program, showed a decline in singing and pitch discrimination skills over the course of 1 year. Taken together, these results are consistent with the idea of musical development as a complex, spiraling and recursive process that is influenced by several factors including type of musical training. Implications for future research are outlined. PMID- 26869967 TI - Effects of Presentation Type and Visual Control in Numerosity Discrimination: Implications for Number Processing? AB - Performance in a non-symbolic comparison task in which participants are asked to indicate the larger numerosity of two dot arrays, is assumed to be supported by the Approximate Number System (ANS). This system allows participants to judge numerosity independently from other visual cues. Supporting this idea, previous studies indicated that numerosity can be processed when visual cues are controlled for. Consequently, distinct types of visual cue control are assumed to be interchangeable. However, a previous study showed that the type of visual cue control affected performance using a simultaneous presentation of the stimuli in numerosity comparison. In the current study, we explored whether the influence of the type of visual cue control on performance disappeared when sequentially presenting each stimulus in numerosity comparison. While the influence of the applied type of visual cue control was significantly more evident in the simultaneous condition, sequentially presenting the stimuli did not completely exclude the influence of distinct types of visual cue control. Altogether, these results indicate that the implicit assumption that it is possible to compare performances across studies with a differential visual cue control is unwarranted and that the influence of the type of visual cue control partly depends on the presentation format of the stimuli. PMID- 26869966 TI - Temporal and Spatial Predictability of an Irrelevant Event Differently Affect Detection and Memory of Items in a Visual Sequence. AB - We examined how the temporal and spatial predictability of a task-irrelevant visual event affects the detection and memory of a visual item embedded in a continuously changing sequence. Participants observed 11 sequentially presented letters, during which a task-irrelevant visual event was either present or absent. Predictabilities of spatial location and temporal position of the event were controlled in 2 * 2 conditions. In the spatially predictable conditions, the event occurred at the same location within the stimulus sequence or at another location, while, in the spatially unpredictable conditions, it occurred at random locations. In the temporally predictable conditions, the event timing was fixed relative to the order of the letters, while in the temporally unpredictable condition; it could not be predicted from the letter order. Participants performed a working memory task and a target detection reaction time (RT) task. Memory accuracy was higher for a letter simultaneously presented at the same location as the event in the temporally unpredictable conditions, irrespective of the spatial predictability of the event. On the other hand, the detection RTs were only faster for a letter simultaneously presented at the same location as the event when the event was both temporally and spatially predictable. Thus, to facilitate ongoing detection processes, an event must be predictable both in space and time, while memory processes are enhanced by temporally unpredictable (i.e., surprising) events. Evidently, temporal predictability has differential effects on detection and memory of a visual item embedded in a sequence of images. PMID- 26869968 TI - Editorial: Variability and Individual Differences in Early Social Perception and Social Cognition. PMID- 26869969 TI - The Impact of Instrument-Specific Musical Training on Rhythm Perception and Production. AB - Studies comparing musicians and non-musicians have shown that musical training can improve rhythmic perception and production. These findings tell us that training can result in rhythm processing advantages, but they do not tell us whether practicing a particular instrument could lead to specific effects on rhythm perception or production. The current study used a battery of four rhythm perception and production tasks that were designed to test both higher- and lower level aspects of rhythm processing. Four groups of musicians (drummers, singers, pianists, string players) and a control group of non-musicians were tested. Within-task differences in performance showed that factors such as meter, metrical complexity, tempo, and beat phase significantly affected the ability to perceive and synchronize taps to a rhythm or beat. Musicians showed better performance on all rhythm tasks compared to non-musicians. Interestingly, our results revealed no significant differences between musician groups for the vast majority of task measures. This was despite the fact that all musicians were selected to have the majority of their training on the target instrument, had on average more than 10 years of experience on their instrument, and were currently practicing. These results suggest that general musical experience is more important than specialized musical experience with regards to perception and production of rhythms. PMID- 26869970 TI - Self-Determination and Meaningful Work: Exploring Socioeconomic Constraints. AB - This study examined a model of meaningful work among a diverse sample of working adults. From the perspectives of Self-Determination Theory and the Psychology of Working Framework, we tested a structural model with social class and work volition predicting SDT motivation variables, which in turn predicted meaningful work. Partially supporting hypotheses, work volition was positively related to internal regulation and negatively related to amotivation, whereas social class was positively related to external regulation and amotivation. In turn, internal regulation was positively related to meaningful work, whereas external regulation and amotivation were negatively related to meaningful work. Indirect effects from work volition to meaningful work via internal regulation and amotivation were significant, and indirect effects from social class to meaningful work via external regulation and amotivation were significant. This study highlights the important relations between SDT motivation variables and meaningful work, especially the large positive relation between internal regulation and meaningful work. However, results also reveal that work volition and social class may play critical roles in predicting internal regulation, external regulation, and amotivation. PMID- 26869971 TI - Memory Updating and Mental Arithmetic. AB - Is domain-general memory updating ability predictive of calculation skills or are such skills better predicted by the capacity for updating specifically numerical information? Here, we used multidigit mental multiplication (MMM) as a measure for calculating skill as this operation requires the accurate maintenance and updating of information in addition to skills needed for arithmetic more generally. In Experiment 1, we found that only individual differences with regard to a task updating numerical information following addition (MUcalc) could predict the performance of MMM, perhaps owing to common elements between the task and MMM. In Experiment 2, new updating tasks were designed to clarify this: a spatial updating task with no numbers, a numerical task with no calculation, and a word task. The results showed that both MUcalc and the spatial task were able to predict the performance of MMM but only with the more difficult problems, while other updating tasks did not predict performance. It is concluded that relevant processes involved in updating the contents of working memory support mental arithmetic in adults. PMID- 26869974 TI - Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account. AB - Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance. PMID- 26869973 TI - Fancy Citrus, Feel Good: Positive Judgment of Citrus Odor, but Not the Odor Itself, Is Associated with Elevated Mood during Experienced Helplessness. AB - Aromatherapy claims that citrus essential oils exert mood lifting effects. Controlled studies, however, have yielded inconsistent results. Notably, studies so far did not control for odor pleasantness, although pleasantness is a critical determinant of emotional responses to odors. This study investigates mood lifting effects of d-(+)-limonene, the most prominent substance in citrus essential oils, with respect to odor quality judgments. Negative mood was induced within 78 participants using a helplessness paradigm (unsolvable social discrimination task). During this task, participants were continuously (mean duration: 19.5 min) exposed to d-(+)-limonene (n = 25), vanillin (n = 26), or diethyl phthalate (n = 27). Participants described their mood (Self-Assessment-Manikin, basic emotion ratings) and judged the odors' quality (intensity, pleasantness, unpleasantness, familiarity) prior to and following the helplessness induction. The participants were in a less positive mood after the helplessness induction (p < 0.001), irrespective of the odor condition. Still, the more pleasant the participants judged the odors, the less effective the helplessness induction was in reducing happiness (p = 0.019). The results show no odor specific mood lifting effect of d (+)-limonene, but indicate a positive effect of odor pleasantness on mood. The study highlights the necessity to evaluate odor judgments in aromatherapy research. PMID- 26869972 TI - Frontal Cortical Asymmetry May Partially Mediate the Influence of Social Power on Anger Expression. AB - When irritated by other people, powerful people usually tend to express their anger explicitly and directly, whereas people in less powerful positions are more likely not to show their feelings freely. The neural mechanism behind power and its influence on expression tendency has been scarcely explored. This study recorded frontal EEG activity at rest and frontal EEG activation while participants were engaged in a writing task describing an anger-eliciting event, in which they were irritated by people with higher or lower social power. Participants' anger levels and expression inclination levels were self-reported on nine-point visual analog Likert scales, and also rated by independent raters based on the essays they had written. The results showed that high social power was indeed associated with greater anger expression tendency and greater left frontal activation than low social power. This is in line with the approach inhibition theory of power. The mid-frontal asymmetric activation served as a partial mediator between social power and expression inclination. This effect may relate to the functions of the prefrontal cortex, which is in charge of information integration and evaluation and the control of motivation direction, as reported by previous studies. PMID- 26869975 TI - How to Best Name a Place? Facilitation and Inhibition of Route Learning Due to Descriptive and Arbitrary Location Labels. AB - Establishing verbal memory traces for non-verbal stimuli was reported to facilitate or inhibit memory for the non-verbal stimuli. We show that these effects are also observed in a domain not indicated before-wayfinding. Fifty three participants followed a guided route in a virtual environment. They were asked to remember half of the intersections by relying on the visual impression only. At the other 50% of the intersections, participants additionally heard a place name, which they were asked to memorize. For testing, participants were teleported to the intersections and were asked to indicate the subsequent direction of the learned route. In Experiment 1, intersections' names were arbitrary (i.e., not related to the visual impression). Here, participants performed more accurately at unnamed intersections. In Experiment 2, intersections' names were descriptive and participants' route memory was more accurate at named intersections. Results have implications for naming places in a city and for wayfinding aids. PMID- 26869976 TI - A Pronoun Analysis of Couples' Support Transactions. AB - The present study collected data about couples' level of relationship quality and their usage of pronouns that express we-ness or separateness in the context of support interactions. The sample consisted of 48 couples in a long-term relationship who provided questionnaire data and participated in two videotaped social support interaction tasks. Couples' videotaped interactions were subsequently coded for the number of personal pronouns-we-words (e.g., we, ours, ourselves) versus you and me-words (e.g., me, mine, you, yours)-used by both partners. PMID- 26869977 TI - The Adapting Mind in the Genomic Era. AB - Genomics and molecular biology has added substantial methods and knowledge to nearly all fields of biology and medicine. In this review we try to demonstrate how genomics and molecular biology is also on the way to have a profound impact on behavioral anthropology, evolutionary psychology, evolutionary sociology, and bio-sociology. We propose that particularly studies on "selection and adaptation" will be influenced profoundly by genomics, for instance via identification of the partially genetic basis of human behavior by "candidate gene studies" and by "genome wide association studies." In addition, epigenetics will lead to a deeper study of the interaction of the genetic basis of a behavior and its environmental regulation. We argue that the "genomic revolution" is much more than merely a new methodological approach, but will change our concepts of human behavior and its development in the evolution of homo. PMID- 26869978 TI - Providing Extrinsic Reward for Test Performance Undermines Long-Term Memory Acquisition. AB - Based on numerous studies showing that testing studied material can improve long term retention more than restudying the same material, it is often suggested that the number of tests in education should be increased to enhance knowledge acquisition. However, testing in real-life educational settings often entails a high degree of extrinsic motivation of learners due to the common practice of placing important consequences on the outcome of a test. Such an effect on the motivation of learners may undermine the beneficial effects of testing on long term memory because it has been shown that extrinsic motivation can reduce the quality of learning. To examine this issue, participants learned foreign language vocabulary words, followed by an immediate test in which one-third of the words were tested and one-third restudied. To manipulate extrinsic motivation during immediate testing, participants received either monetary reward contingent on test performance or no reward. After 1 week, memory for all words was tested. In the immediate test, reward reduced correct recall and increased commission errors, indicating that reward reduced the number of items that can benefit from successful retrieval. The results in the delayed test revealed that reward additionally reduced the gain received from successful retrieval because memory for initially successfully retrieved words was lower in the reward condition. However, testing was still more effective than restudying under reward conditions because reward undermined long-term memory for concurrently restudied material as well. These findings indicate that providing performance-contingent reward in a test can undermine long-term knowledge acquisition. PMID- 26869980 TI - "How Much is that Player in the Window? The One with the Early Birthday?" Relative Age Influences the Value of the Best Soccer Players, but Not the Best Businesspeople. PMID- 26869979 TI - Am I Overweight? A Longitudinal Study on Parental and Peers Weight-Related Perceptions on Dietary Behaviors and Weight Status Among Adolescents. AB - OBJECTIVE: An investigation of the interplay between various types of adolescents' perceptions of weight status in predicting adolescents' nutrition behavior and their body mass was conducted. In particular, it was hypothesized that the relationship between parental and peers' perceptions of their own weight status (reported by adolescents) and objectively measured weight status of adolescents would be mediated by three types of adolescents' weight status perceptions (adolescents' own weight perceptions, parental perceptions of adolescents' weight status perceived by participants, and peers' perceptions of adolescents' weight status perceived by participants) and by adolescents' nutrition behaviors. DESIGN: Data were collected twice, with a 13-month follow up. Participants (N = 1096) were aged 14-20, with BMI ranging from 16.20 to 41.21. Multiple mediation analysis with two sequential mediators was applied. MAIN OUTCOME MEASURES: At the baseline adolescents completed the questionnaire assessing their nutrition behaviors and weight status perceptions. Weight and height were measured objectively at baseline and follow-up. RESULTS: Two types of weight perceptions (adolescents' own weight status perceptions, peers' perceptions of adolescents' weight status reported by participants), and adolescents' nutrition behaviors mediated the relationship between the others' own weight perceptions and adolescents' weight status. No indirect effects of others' own weight perceptions on adolescents' weight status through parental perceptions were found. CONCLUSION: Adolescents' nutrition behaviors and body weight status depend on what they think about their own weight status and what they think of their peers' perceptions, but do not depend on what adolescents think of their parents' perceptions. PMID- 26869981 TI - Modeling the Relations Among Morphological Awareness Dimensions, Vocabulary Knowledge, and Reading Comprehension in Adult Basic Education Students. AB - This study extended the findings of Tighe and Schatschneider (2015) by investigating the predictive utility of separate dimensions of morphological awareness as well as vocabulary knowledge to reading comprehension in adult basic education (ABE) students. We competed two- and three-factor structural equation models of reading comprehension. A three-factor model of real word morphological awareness, pseudoword morphological awareness, and vocabulary knowledge emerged as the best fit and accounted for 79% of the reading comprehension variance. The results indicated that the constructs contributed jointly to reading comprehension; however, vocabulary knowledge was the only potentially unique predictor (p = 0.052), accounting for an additional 5.6% of the variance. This study demonstrates the feasibility of applying a latent variable modeling approach to examine individual differences in the reading comprehension skills of ABE students. Further, this study replicates the findings of Tighe and Schatschneider (2015) on the importance of differentiating among dimensions of morphological awareness in this population. PMID- 26869982 TI - Getting under the Skin: Report from the International Psoriasis Council Workshop on the Role of Stress in Psoriasis. AB - Psoriasis is a chronic inflammatory skin condition with significant physical and psychosocial comorbidity. A workshop of leading experts in dermatology and psychology with the purpose of better understanding the current role of psychological comorbidities in psoriasis was held by the International Psoriasis Council in November 2013. The role of stress reactivity with a focus on the hypothalamic-pituitary-adrenal axis was emphasized. While cognitive behavioral therapy remains the most extensively studied and successful treatment strategy in patients with psoriasis and various psychological comorbidities, new and innovative interventions such as online-based therapies have recently emerged. Strategies and recommendations toward approaching psychological comorbidities are discussed. PMID- 26869983 TI - Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression. AB - Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID- 26869984 TI - From Self to Nonself: The Nonself Theory. AB - The maintenance/strength of self is a very core concept in Western psychology and is particularly relevant to egoism, a process that draws on the hedonic principle in pursuit of desires. Contrary to this and based on Buddhism, a nonself cultivating process aims to minimize or extinguish the self and avoid desires, leading to egolessness or selflessness. The purpose of this paper is to present the Nonself Theory (NT). The universal Mandala Model of Self (MMS) was developed to describe the well-functioning self in various cultures. The end goal of the self is to attain authentic and durable happiness. Given that the nonself is considered a well-functioning self, the MMS is suitable for constructing the NT. The ego and nonself aspects of psychological self-functioning and their underlying processes are compared, drawing on the four concepts of the MMS: biology, ideal person, knowledge/wisdom and action. The ego engages in psychological activities to strengthen the self, applying the hedonic principle of seeking desire-driven pleasure. In contrast, a nonself approach involves execution of the self-cultivation principle, which involves three ways: giving up desires, displaying compassion, practicing meditation and seeking understanding Buddhist wisdom. These three ways have the goal of seeing through and overcoming the illusion of the self to achieve a deep transformation integrally connected to the experience of eliminating the sense of self and its psychological structures. In addition, the NT provides a comprehensive framework to account for nonself plus-compassion-related activities or experiences such as altruism, mindfulness, mediation, mysterious/peak experiences, elimination of death anxiety and moral conduct. The NT offers possible answers that might lead to a more comprehensive understanding of human beings and the deeper meaning of life, toward the ultimate goal of a well-functioning self. An examination of possible clinical applications and theoretical directions for future research in nonself psychology are provided. PMID- 26869985 TI - Corrigendum: Arousal and exposure duration affect forward step initiation. AB - [This corrects the article on p. 1667 in vol. 6, PMID: 26579048.]. PMID- 26869986 TI - Cerebral Microcirculation during Experimental Normovolaemic Anemia. AB - Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia. Experimental studies suggest that anemia leads to cerebral hypoxia and increased rates of infarction, but the lack of clinical equipoise, when testing the cerebral effects of transfusion among critically injured patients, supports the need of experimental studies. The aim of this study was to quantify cerebral microcirculation and the potential presence of axonal damage in an experimental model exposed to normovolaemic anemia, with the intention of describing possible limitations within management practices in critically ill patients. Under non recovered anesthesia, six Merino sheep were instrumented using an intracardiac transeptal catheter to inject coded microspheres into the left atrium to ensure systemic and non-chaotic distribution. Cytometric analyses quantified cerebral microcirculation at specific regions of the brain. Amyloid precursor protein staining was used as an indicator of axonal damage. Animals were exposed to normovolaemic anemia by blood extractions from the indwelling arterial catheter with simultaneous fluid replacement through a venous central catheter. Simultaneous data recording from cerebral tissue oxygenation, intracranial pressure, and cardiac output was monitored. A regression model was used to examine the effects of anemia on microcirculation with a mixed model to control for repeated measures. Homogeneous and normal cerebral microcirculation with no evidence of axonal damage was present in all cerebral regions, with no temporal variability, concluding that acute normovolaemic anemia does not result in short term effects on cerebral microcirculation in the ovine brain. PMID- 26869987 TI - A Rare Cervical Dystonia Mimic in Adults: Congenital Muscular Torticollis (Fibromatosis colli), a Follow-up. AB - Neglected or undiagnosed congenital muscular torticollis in adults is quite rare, although it is the third most common congenital deformity in the newborn (1). When left untreated at an early age, deficits in lateral and rotational range of motion can occur along with irreversible facial and skeletal deformities that develop over time. Subtle cases can go unnoticed until early adulthood, with predominant fibrotic replacement in the sternocleidomastoid (SCM) making physical therapy and chemodenervation mostly ineffective. Surgical intervention, in these cases, can prove effective in alleviating pain, improving function and cosmesis (2). We report an update on a previously reported case, misdiagnosed as cervical dystonia, which had undergone partial myectomy of the anterior belly of the SCM with some relief of symptoms but without total resolution after the correct diagnosis of fibromatosis colli (3). PMID- 26869989 TI - A Non-inflammatory Role for Microglia in Autism Spectrum Disorders. AB - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, difficulties with language, and repetitive/restricted behaviors. The etiology of ASD is still largely unclear, but immune dysfunction and abnormalities in synaptogenesis have repeatedly been implicated as contributing to the disease phenotype. However, an understanding of how and if these two processes are related has not firmly been established. As non-inflammatory roles of microglia become increasingly recognized as critical to normal neurodevelopment, it is important to consider how dysfunction in these processes might explain the seemingly disparate findings of immune dysfunction and aberrant synaptogenesis seen in ASD. In this review, we highlight research demonstrating the importance of microglia to the development of normal neural networks, review recent studies demonstrating abnormal microglia in autism, and discuss how the relationship between these processes may contribute to the development of autism and other neurodevelopmental disorders at the cellular level. PMID- 26869990 TI - Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types. AB - The mechanisms involved in traumatic brain injury have yet to be fully characterized. One mechanism that, especially in high-energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation, and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer-plate model is an in vitro high-energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation, and shock waves inside the well and cell medium. We have found the flyer-plate model to be efficient, reproducible, and easy to control. In this study, we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose dependent manner. Using gene expression microarray, a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 h post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies. PMID- 26869988 TI - Toward Precision Psychiatry: Statistical Platform for the Personalized Characterization of Natural Behaviors. AB - There is a critical need for new analytics to personalize behavioral data analysis across different fields, including kinesiology, sports science, and behavioral neuroscience. Specifically, to better translate and integrate basic research into patient care, we need to radically transform the methods by which we describe and interpret movement data. Here, we show that hidden in the "noise," smoothed out by averaging movement kinematics data, lies a wealth of information that selectively differentiates neurological and mental disorders such as Parkinson's disease, deafferentation, autism spectrum disorders, and schizophrenia from typically developing and typically aging controls. In this report, we quantify the continuous forward-and-back pointing movements of participants from a large heterogeneous cohort comprising typical and pathological cases. We empirically estimate the statistical parameters of the probability distributions for each individual in the cohort and report the parameter ranges for each clinical group after characterization of healthy developing and aging groups. We coin this newly proposed platform for individualized behavioral analyses "precision phenotyping" to distinguish it from the type of observational-behavioral phenotyping prevalent in clinical studies or from the "one-size-fits-all" model in basic movement science. We further propose the use of this platform as a unifying statistical framework to characterize brain disorders of known etiology in relation to idiopathic neurological disorders with similar phenotypic manifestations. PMID- 26869991 TI - Multiple Pituitary Adenomas: A Systematic Review. AB - PubMed, Scopus, and Web of Science Core Collection databases were systematically searched for studies reporting synchronous double or multiple pituitary adenomas (MPA), a rare clinical condition, with a vague pathogenesis. Multiple adenomas of the pituitary gland are referred to as morphologically and/or immunocytochemically distinct tumors that are frequently small-sized and hormonally non-functional, to account for the low detection rate. There is no general agreement on how to classify MPA, various criteria, such as tumor contiguity, immunoreactivity, and clonality analysis are being used. Among the component tumors, prolactin (PRL)-immunopositive adenomas are highly prevalent, albeit mute in the majority of cases. The most frequent clinical presentation of MPA is Cushing's syndrome, given the fact that in more than 50% of reported cases at least one lesion stains for adrenocorticotrophic hormone (ACTH). Plurihormonal hyperactivity may be diagnosed in a patient with MPA when more than one tumor is clinically active (e.g., ACTH and PRL) or in cases with at least one composite tumor (e.g., GH and PRL), to complicate the clinical scenario. Specific challenges associated with MPA include high surgical failure rates, enforcing second-look surgery in certain cases, and difficult preoperative neuroradiological imaging evaluation, with an overall sensitivity of only 25% for magnetic resonance imaging to detect distinct multiple tumors. Alternatively, minor pituitary imaging abnormalities may raise suspicion, as these are not uncommon. Postoperative immunohistochemistry is mandatory and in conjunction to electron microscopy scanning and testing for transcription factors (i.e., Pit-1, T-pit, and SF-1) accurately define and classify the distinct cytodifferentiation of MPA. PMID- 26869992 TI - Fenofibrate Induces Ketone Body Production in Melanoma and Glioblastoma Cells. AB - Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. PMID- 26869993 TI - Possible Role of GnIH as a Mediator between Adiposity and Impaired Testicular Function. AB - The aim of the present study was to evaluate the roles of gonadotropin-inhibitory hormone (GnIH) as an endocrine link between increasing adiposity and impaired testicular function in mice. To achieve this, the effect of GnIH on changes in nutrients uptake and hormonal synthesis/action in the adipose tissue and testis was investigated simultaneously by in vivo study and separately by in vitro study. Mice were treated in vivo with different doses of GnIH for 8 days. In the in vitro study, adipose tissue and testes of mice were cultured with different doses of GnIH with or without insulin or LH for 24 h at 37 degrees C. The GnIH treatment in vivo showed increased food intake, upregulation of glucose transporter 4 (GLUT4), and increased uptake of triglycerides (TGs) in the adipose tissue. These changes may be responsible for increased accumulation of fat in white adipose tissue, resulting in increase in the body mass. Contrary to the adipose tissue, treatment with GnIH both in vivo and in vitro showed decreased uptake of glucose by downregulation of glucose transporter 8 (GLUT8) expressions in the testis, which in turn resulted in the decreased synthesis of testosterone. The GnIH treatment in vivo also showed the decreased expression of insulin receptor protein in the testis, which may also be responsible for the decreased testicular activity in the mice. These findings thus suggest that GnIH increases the uptake of glucose and TGs in the adipose tissue, resulting in increased accumulation of fat, whereas simultaneously in the testis, GnIH suppressed the GLUT8-mediated glucose uptake, which in turn may be responsible for decreased testosterone synthesis. This study thus demonstrates GnIH as mediator of increasing adiposity and impaired testicular function in mice. PMID- 26869994 TI - In Utero Bisphenol A Exposure Induces Abnormal Neuronal Migration in the Cerebral Cortex of Mice. AB - Bisphenol A (BPA) has been known to have endocrine-disrupting activity to induce reproductive and behavioral abnormalities in offspring of laboratory animal species. However, morphological basis of this abnormality during brain development is largely unknown. Cerebral cortex plays a crucial role in higher brain function, and its precisely laminated structure is formed by neuronal migration. In the present study, transfecting a plasmid (pCAG-mCherry) by in utero electroporation (IUE), we visualized developing neurons and investigated the possible effects of in utero BPA exposure on neuronal migration. Pregnant mice were exposed to BPA by osmotic pump at estimated daily doses of 0, 40 (BPA 40), or 400 (BPA-400) MUg/kg from embryonic day 14.5 (E14.5) to E18.5. IUE was performed at E14.5 and neuronal migration was analyzed at E18.5. Compared with the control group, neuronal migration in the cortical plate was significantly decreased in the BPA-40 group; however, there was no significant difference in the BPA-400 group. Among several neuronal migration-related genes and cortical layer-specific genes, TrkB in the BPA-400 group was found significantly upregulated. In conclusion, in utero exposure to low BPA dose was found to disrupt neuronal migration in the cerebral cortex in a dose-specific manner. PMID- 26869996 TI - Isolation and Identification of Plant Growth Promoting Rhizobacteria from Cucumber Rhizosphere and Their Effect on Plant Growth Promotion and Disease Suppression. AB - Plant growth promoting rhizobacteria (PGPR) are the rhizosphere bacteria that may be utilized to augment plant growth and suppress plant diseases. The objectives of this study were to identify and characterize PGPR indigenous to cucumber rhizosphere in Bangladesh, and to evaluate their ability to suppress Phytophthora crown rot in cucumber. A total of 66 isolates were isolated, out of which 10 (PPB1, PPB2, PPB3, PPB4, PPB5, PPB8, PPB9, PPB10, PPB11, and PPB12) were selected based on their in vitro plant growth promoting attributes and antagonism of phytopathogens. Phylogenetic analysis of 16S rRNA sequences identified these isolates as new strains of Pseudomonas stutzeri, Bacillus subtilis, Stenotrophomonas maltophilia, and Bacillus amyloliquefaciens. The selected isolates produced high levels (26.78-51.28 MUg mL(-1)) of indole-3-acetic acid, while significant acetylene reduction activities (1.79-4.9 MUmole C2H4 mg(-1) protein h(-1)) were observed in eight isolates. Cucumber plants grown from seeds that were treated with these PGPR strains displayed significantly higher levels of germination, seedling vigour, growth, and N content in root and shoot tissue compared to non-treated control plants. All selected isolates were able to successfully colonize the cucumber roots. Moreover, treating cucumber seeds with these isolates significantly suppressed Phytophthora crown rot caused by Phytophthora capsici, and characteristic morphological alterations in P. capsici hyphae that grew toward PGPR colonies were observed. Since these PGPR inoculants exhibited multiple traits beneficial to the host plants, they may be applied in the development of new, safe, and effective seed treatments as an alternative to chemical fungicides. PMID- 26869997 TI - Sulfur Biogeochemistry of an Oil Sands Composite Tailings Deposit. AB - Composite tailings (CT), an engineered, alkaline, saline mixture of oil sands tailings (FFT), processed sand and gypsum (CaSO4; 1 kg CaSO4 per m(3) FFT) are used as a dry reclamation strategy in the Alberta Oil Sands Region (AOSR). It is estimated that 9.6 * 10(8) m(3) of CT are either in, or awaiting emplacement in surface pits within the AOSR, highlighting their potential global importance in sulfur cycling. Here, in the first CT sulfur biogeochemistry investigation, integrated geochemical, pyrosequencing and lipid analyses identified high aqueous concentrations of ?H2S (>300 MUM) and highly altered sulfur compounds composition; low cell biomass (3.3 * 10(6)- 6.0 * 10(6) cells g(-1)) and modest bacterial diversity (H' range between 1.4 and 1.9) across 5 depths spanning 34 m of an in situ CT deposit. Pyrosequence results identified a total of 29,719 bacterial 16S rRNA gene sequences, representing 131 OTUs spanning19 phyla including 7 candidate divisions, not reported in oil sands tailings pond studies to date. Legacy FFT common phyla, notably, gamma and beta Proteobacteria, Firmicutes, Actinobacteria, and Chloroflexi were represented. However, overall CT microbial diversity and PLFA values were low relative to other contexts. The identified known sulfate/sulfur reducing bacteria constituted at most 2% of the abundance; however, over 90% of the 131 OTUs identified are capable of sulfur metabolism. While PCR biases caution against overinterpretation of pyrosequence surveys, bacterial sequence results identified here, align with phospholipid fatty acid (PLFA) and geochemical results. The highest bacterial diversities were associated with the depth of highest porewater [?H2S] (22-24 m) and joint porewater co-occurrence of Fe(2+) and ?H2S (6-8 m). Three distinct bacterial community structure depths corresponded to CT porewater regions of (1) shallow evident Fe((II)) (<6 m), (2) co-occurring Fe((II)) and ?H2S (6-8 m) and (3) extensive ?H2S (6-34 m) (UniFrac). Candidate divisions GNO2, NKB19 and Spam were present only at 6-8 m associated with co-occurring [Fe((II))] and [?H2S]. Collectively, results indicate that CT materials are differentiated from other sulfur rich environments by modestly diverse, low abundance, but highly sulfur active and more enigmatic communities (7 candidate divisions present within the 19 phyla identified). PMID- 26869998 TI - Race Against Antimicrobial Resistance Requires Coordinated Action - An Overview. AB - Resistance developed by microbes is challenging success stories of treatment of infectious diseases with anti-microbials. Developing new antimicrobials against these resistant organisms does not progress at the same speed. In an effort to address this key issue, this work overviews the role of different stakeholders and discusses preventative and control measures for effective management of available resources. Roles and concerns of physicians, pharmacists and the public are also discussed. More than anything, this situation requires immediate action to establish antimicrobial stewardship program, control over the counter sale and promote public awareness. The paper also confronts the idea of curbing the use of antimicrobials using mass media, while detailing the consequences of non therapeutic use. The role of policy makers in taking global action is essential to establishing authority or agency for formulating national guidelines and regulations for prudently using antimicrobials. To do this, this paper recommend the establishment of a global fund. In conclusion, the race against resistance is a collective responsibility requiring coordinated action at local, national, regional and international levels to ensure sustained utilization of antimicrobials. PMID- 26869995 TI - The Role of Steroid Hormones in the Modulation of Neuroinflammation by Dietary Interventions. AB - Steroid hormones, such as sex hormones and glucocorticoids, have been demonstrated to play a role in different cellular processes in the central nervous system, ranging from neurodevelopment to neurodegeneration. Environmental factors, such as calorie intake or fasting frequency, may also impact on such processes, indicating the importance of external factors in the development and preservation of a healthy brain. The hypothalamic-pituitary-adrenal axis and glucocorticoid activity play a role in neurodegenerative processes, including in disorders such as in Alzheimer's and Parkinson's diseases. Sex hormones have also been shown to modulate cognitive functioning. Inflammation is a common feature in neurodegenerative disorders, and sex hormones/glucocorticoids can act to regulate inflammatory processes. Intermittent fasting can protect the brain against cognitive decline that is induced by an inflammatory stimulus. On the other hand, obesity increases susceptibility to inflammation, while metabolic syndromes, such as diabetes, are associated with neurodegeneration. Consequently, given that gonadal and/or adrenal steroids may significantly impact the pathophysiology of neurodegeneration, via their effect on inflammatory processes, this review focuses on how environmental factors, such as calorie intake and intermittent fasting, acting through their modulation of steroid hormones, impact on inflammation that contributes to cognitive and neurodegenerative processes. PMID- 26869999 TI - Transmission Dynamics of Rift Valley Fever Virus: Effects of Live and Killed Vaccines on Epizootic Outbreaks and Enzootic Maintenance. AB - Rift Valley fever virus (RVFV) is an arthropod-borne viral pathogen that causes significant morbidity and mortality in small ruminants throughout Africa and the Middle East. Due to the sporadic and explosive nature of RVF outbreaks, vaccination has proved challenging to reduce RVFV infection in the ruminant population. Currently, there are two available types of vaccines, live and killed, in endemic areas. In this study, two mathematical models have been developed to explore the impact of live and killed vaccines on the transmission dynamics of RVFV. We demonstrate in general that vaccination helps reduce the severity of RVF outbreaks and that less delay in implementation and more vaccination attempts and effective vaccines can reduce the outbreak magnitude and the endemic number of RVFV. However, an introduction of a number of ruminants vaccinated by live vaccines in RVFV-free areas may cause an outbreak and RVFV may become endemic if there is sustained use of live vaccines. Other factors that are the important determinants of RVF outbreaks include: unsustained vaccination programs, recruitment of susceptible ruminants, and the seasonal abundance of mosquitoes. PMID- 26870000 TI - Potentiating the Heat Inactivation of Escherichia coli O157:H7 in Ground Beef Patties by Natural Antimicrobials. AB - Escherichia coli O157: H7 (EHEC) is a major foodborne pathogen largely transmitted to humans through the consumption of undercooked ground beef. This study investigated the efficacy of two food-grade, plant-derived antimicrobials, namely rutin (RT), and resveratrol (RV) with or without chitosan (CH) in enhancing EHEC inactivation in undercooked hamburger patties. Further, the effect of aforementioned treatments on beef color and lipid oxidation was analyzed. Additionally, the deleterious effects of these antimicrobial treatments on EHEC was determined using scanning electron microscopy (SEM). Ground beef was inoculated with a five-strain mixture of EHEC (7.0 log CFU/g), followed by the addition of RT (0.05%, 0.1% w/w) or RV (0.1, 0.2% w/w) with or without CH (0.01% w/w). The meat was formed into patties (25 g) and stored at 4 degrees C for 5 days. On days 1, 3, and 5, the patties were cooked (65 degrees C, medium rare) and surviving EHEC was enumerated. The effect of these treatments on meat color and lipid oxidation during storage was also determined as per American Meat Science Association guidelines. The study was repeated three times with duplicate samples of each treatment. Both RT and RV enhanced the thermal destruction of EHEC, and reduced the pathogen load by at least 3 log CFU/g compared to control (P < 0.05). The combination of RT or RV with CH was found to be more effective, and reduced EHEC by 5 log CFU/g (P < 0.05). EHEC counts in uncooked patties did not decline during storage for 5 days (P > 0.05). Moreover, patties treated with RV plus CH were more color stable with higher a(*) values (P < 0.05). SEM results revealed that heat treatment with antimicrobials (CH + RV 0.2%) resulted in complete destruction of EHEC cells and extrusion of intracellular contents. Results suggest that the aforementioned antimicrobials could be used for enhancing the thermal inactivation of EHEC in undercooked patties; however, detailed sensory studies are warranted. PMID- 26870002 TI - Editorial: Computational Systems Biology of Pathogen-Host Interactions. PMID- 26870001 TI - A Critical Role of Bacterioferritin in Salmonella pullorum-Induced IFN-beta Expression in DF-1 Cells. AB - Salmonella enterica serovar Pullorum (S. pullorum) causes pullorum disease in poultry and results in great economic losses to the poultry industry. Although an eradication program has been successfully performed in some countries, it remains a major threat to countries with poor poultry disease surveillance. Currently there are no effective control measures for pullorum disease except eradication. In particular, the pathogenesis of S. pullorum infection is still largely unknown. Here we identified bacterioferritin (Bfr) as a major antigen of S. pullorum to elicit a humoral immune response. Furthermore, we demonstrate that Bfr induces activation of IFN-beta promoter and mRNA expression in DF-1 cells, and that the amino acids 1-50 form a critical domain involved in IFN-beta expression. Moreover, we found that the p38 MAPK signaling pathway was essential for Bfr-induced IFN-beta expression. Importantly, S. pullorum-induced IFN-beta expression was totally abolished by deficiency of Bfr in the bacteria, indicating that Bfr plays a critical role in S. pullorum induced IFN-beta expression in DF-1 cells. Our findings provide new insights into the molecular mechanisms of the host response to S. pullorum infection. PMID- 26870004 TI - VirusTAP: Viral Genome-Targeted Assembly Pipeline. AB - Although next-generation sequencing (NGS) technology provides a comprehensive means with which to identify potential pathogens from clinical specimens, simple and user-friendly bioinformatics pipelines are expected to obtain the entire viral genome sequence, subsequently providing traceability, based on extensive molecular phylogenetic analyses. We have developed a web-based integrated NGS analysis tool for the viral genome (virus genome-targeted assembly pipeline: VirusTAP), which includes extensive sequence subtraction of host- or bacteria related NGS reads prior to de novo assembly, leading to the prompt and accurate assembly of viral genome sequences from metagenomic NGS reads. The VirusTAP web site is at https://gph.niid.go.jp/cgi-bin/virustap/index.cgi/. PMID- 26870003 TI - Ig Constant Region Effects on Variable Region Structure and Function. AB - The adaptive humoral immune response is responsible for the generation of antimicrobial proteins known as immunoglobulin molecules or antibodies. Immunoglobulins provide a defense system against pathogenic microbes and toxins by targeting them for removal and/or destruction. Historically, antibodies have been thought to be composed of distinct structural domains known as the variable and constant regions that are responsible for antigen binding and mediating effector functions such as opsonization and complement activation, respectively. These domains were thought to be structurally and functionally independent. Recent work has revealed however, that in some families of antibodies, the two regions can influence each other. We will discuss the body of work that led to these observations, as well as the mechanisms that have been proposed to explain how these two different antibody regions may interact in the function of antigen binding. PMID- 26870006 TI - Pharmacokinetic and Pharmacodynamic Integration and Modeling of Enrofloxacin in Swine for Escherichia coli. AB - The aim of this study was to optimize the dose regimens of enrofloxacin to reduce the development of fluoroquinolone resistance in Escherichia coli (E.coli) using pharmacokinetic/pharmacodynamic (PK/PD) modeling approach. The single dose (2.5 mg/kg body weight) of enrofloxacin was administered intramuscularly (IM) to the healthy pigs. Using cannulation, the pharmacokinetic properties, including peak concentration (C max), time to reach C max (T max), and area under the curve (AUC), were determined in plasma and ileum content. The C max, T max, and AUC in the plasma were 1.09 +/- 0.11 MUg/mL, 1.27 +/- 0.35 h, and 12.70 +/- 2.72 MUg.h/mL, respectively. While in ileum content, the C max, T max, and AUC were 7.07 +/- 0.26 MUg/mL, 5.54 +/- 0.42 h, and 136.18 +/- 12.50 MUg.h/mL, respectively. Based on the minimum inhibitory concentration (MIC) data of 918 E. coli isolates, an E. coli O101/K99 strain (enrofloxacin MIC = 0.25 MUg/mL) was selected for pharmacodynamic studies. The in vitro minimum bactericidal concentration (MBC), mutant prevention concentration (MPC), and ex vivo time killing curves for enrofloxacin in ileum content were established against the selected E. coli O101/K99 strain. Integrating the in vivo pharmacokinetic data and ex vivo pharmacodynamic data, a sigmoid E max (Hill) equation was established to provide values for ileum content of AUC24h/MIC producing, bactericidal activity (52.65 h), and virtual eradication of bacteria (78.06 h). A dosage regimen of 1.96 mg/kg every 12 h for 3 days should be sufficient in the treatment of E. coli. PMID- 26870005 TI - Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model. AB - The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of infection toward disease in human lungs. PMID- 26870007 TI - The TCA Pathway is an Important Player in the Regulatory Network Governing Vibrio alginolyticus Adhesion Under Adversity. AB - Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway) might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, quantitative Real-Time PCR (qPCR), RNAi, and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity, and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that (1) the TCA pathway plays a key role in V. alginolyticus adhesion: (2) the TCA pathway is sensitive to environmental stresses. PMID- 26870009 TI - Editorial: Advances in Aspergillus fumigatus Pathobiology. PMID- 26870011 TI - Metabolic Capabilities of Microorganisms Involved in and Associated with the Anaerobic Oxidation of Methane. AB - In marine sediments the anaerobic oxidation of methane with sulfate as electron acceptor (AOM) is responsible for the removal of a major part of the greenhouse gas methane. AOM is performed by consortia of anaerobic methane-oxidizing archaea (ANME) and their specific partner bacteria. The physiology of these organisms is poorly understood, which is due to their slow growth with doubling times in the order of months and the phylogenetic diversity in natural and in vitro AOM enrichments. Here we study sediment-free long-term AOM enrichments that were cultivated from seep sediments sampled off the Italian Island Elba (20 degrees C; hereon called E20) and from hot vents of the Guaymas Basin, Gulf of California, cultivated at 37 degrees C (G37) or at 50 degrees C (G50). These enrichments were dominated by consortia of ANME-2 archaea and Seep-SRB2 partner bacteria (E20) or by ANME-1, forming consortia with Seep-SRB2 bacteria (G37) or with bacteria of the HotSeep-1 cluster (G50). We investigate lipid membrane compositions as possible factors for the different temperature affinities of the different ANME clades and show autotrophy as characteristic feature for both ANME clades and their partner bacteria. Although in the absence of additional substrates methane formation was not observed, methanogenesis from methylated substrates (methanol and methylamine) could be quickly stimulated in the E20 and the G37 enrichment. Responsible for methanogenesis are archaea from the genus Methanohalophilus and Methanococcoides, which are minor community members during AOM (1-70/00 of archaeal 16S rRNA gene amplicons). In the same two cultures also sulfur disproportionation could be quickly stimulated by addition of zero-valent colloidal sulfur. The isolated partner bacteria are likewise minor community members (1-90/00 of bacterial 16S rRNA gene amplicons), whereas the dominant partner bacteria (Seep-SRB1a, Seep-SRB2, or HotSeep-1) did not grow on elemental sulfur. Our results support a functioning of AOM as syntrophic interaction of obligate methanotrophic archaea that transfer non-molecular reducing equivalents (i.e., via direct interspecies electron transfer) to obligate sulfate-reducing partner bacteria. Additional katabolic processes in these enrichments but also in sulfate methane interfaces are likely performed by minor community members. PMID- 26870010 TI - Biological Stability of Drinking Water: Controlling Factors, Methods, and Challenges. AB - Biological stability of drinking water refers to the concept of providing consumers with drinking water of same microbial quality at the tap as produced at the water treatment facility. However, uncontrolled growth of bacteria can occur during distribution in water mains and premise plumbing, and can lead to hygienic (e.g., development of opportunistic pathogens), aesthetic (e.g., deterioration of taste, odor, color) or operational (e.g., fouling or biocorrosion of pipes) problems. Drinking water contains diverse microorganisms competing for limited available nutrients for growth. Bacterial growth and interactions are regulated by factors, such as (i) type and concentration of available organic and inorganic nutrients, (ii) type and concentration of residual disinfectant, (iii) presence of predators, such as protozoa and invertebrates, (iv) environmental conditions, such as water temperature, and (v) spatial location of microorganisms (bulk water, sediment, or biofilm). Water treatment and distribution conditions in water mains and premise plumbing affect each of these factors and shape bacterial community characteristics (abundance, composition, viability) in distribution systems. Improved understanding of bacterial interactions in distribution systems and of environmental conditions impact is needed for better control of bacterial communities during drinking water production and distribution. This article reviews (i) existing knowledge on biological stability controlling factors and (ii) how these factors are affected by drinking water production and distribution conditions. In addition, (iii) the concept of biological stability is discussed in light of experience with well-established and new analytical methods, enabling high throughput analysis and in-depth characterization of bacterial communities in drinking water. We discussed, how knowledge gained from novel techniques will improve design and monitoring of water treatment and distribution systems in order to maintain good drinking water microbial quality up to consumer's tap. A new definition and methodological approach for biological stability is proposed. PMID- 26870012 TI - Identification of Conserved and Potentially Regulatory Small RNAs in Heterocystous Cyanobacteria. AB - Small RNAs (sRNAs) are a growing class of non-protein-coding transcripts that participate in the regulation of virtually every aspect of bacterial physiology. Heterocystous cyanobacteria are a group of photosynthetic organisms that exhibit multicellular behavior and developmental alternatives involving specific transcriptomes exclusive of a given physiological condition or even a cell type. In the context of our ongoing effort to understand developmental decisions in these organisms we have undertaken an approach to the global identification of sRNAs. Using differential RNA-Seq we have previously identified transcriptional start sites for the model heterocystous cyanobacterium Nostoc sp. PCC 7120. Here we combine this dataset with a prediction of Rho-independent transcriptional terminators and an analysis of phylogenetic conservation of potential sRNAs among 89 available cyanobacterial genomes. In contrast to predictive genome-wide approaches, the use of an experimental dataset comprising all active transcriptional start sites (differential RNA-Seq) facilitates the identification of bona fide sRNAs. The output of our approach is a dataset of predicted potential sRNAs in Nostoc sp. PCC 7120, with different degrees of phylogenetic conservation across the 89 cyanobacterial genomes analyzed. Previously described sRNAs appear among the predicted sRNAs, demonstrating the performance of the algorithm. In addition, new predicted sRNAs are now identified that can be involved in regulation of different aspects of cyanobacterial physiology, including adaptation to nitrogen stress, the condition that triggers differentiation of heterocysts (specialized nitrogen-fixing cells). Transcription of several predicted sRNAs that appear exclusively in the genomes of heterocystous cyanobacteria is experimentally verified by Northern blot. Cell specific transcription of one of these sRNAs, NsiR8 (nitrogen stress-induced RNA 8), in developing heterocysts is also demonstrated. PMID- 26870014 TI - Human Microbiota of the Argentine Population- A Pilot Study. AB - The human microbiota is the collection of microorganisms living in or on the human body. An imbalance or dysbiosis in these microbial communities can be associated with a wide variety of human diseases (Petersen and Round, 2014; Pham and Lawley, 2014; Zaura et al., 2014). Moreover, when the microbiota of the same body sites is compared between different healthy individuals, specific microbial community features are apparent (Li et al., 2012; Yatsunenko et al., 2012; Oh et al., 2014; Relman, 2015). In addition, specific selective pressures are found at distinct body sites leading to different patterns in microbial community structure and composition (Costello et al., 2009; Consortium, 2012b; Zhou et al., 2013). Because of these natural variations, a comprehensive characterization of the healthy microbiota is critical for predicting alterations related to diseases. This characterization should be based on a broad healthy population over time, geography, and culture (Yatsunenko et al., 2012; Shetty et al., 2013; Leung et al., 2015; Ross et al., 2015). The study of healthy individuals representing different ages, cultural traditions, and ethnic origins will enable to understand how the associated microbiota varies between populations and respond to different lifestyles. It is important to address these natural variations in order to later detect variations related to disease. PMID- 26870008 TI - Bacterial Toxins as Pathogen Weapons Against Phagocytes. AB - Bacterial toxins are virulence factors that manipulate host cell functions and take over the control of vital processes of living organisms to favor microbial infection. Some toxins directly target innate immune cells, thereby annihilating a major branch of the host immune response. In this review we will focus on bacterial toxins that act from the extracellular milieu and hinder the function of macrophages and neutrophils. In particular, we will concentrate on toxins from Gram-positive and Gram-negative bacteria that manipulate cell signaling or induce cell death by either imposing direct damage to the host cells cytoplasmic membrane or enzymatically modifying key eukaryotic targets. Outcomes regarding pathogen dissemination, host damage and disease progression will be discussed. PMID- 26870015 TI - Callose Deposition in Plasmodesmata and Viroid Invasion of the Shoot Apical Meristem. PMID- 26870013 TI - Reservoirs of Non-baumannii Acinetobacter Species. AB - Acinetobacter spp. are ubiquitous gram negative and non-fermenting coccobacilli that have the ability to occupy several ecological niches including environment, animals and human. Among the different species, Acinetobacter baumannii has evolved as global pathogen causing wide range of infection. Since the implementation of molecular techniques, the habitat and the role of non-baumannii Acinetobacter in human infection have been elucidated. In addition, several new species have been described. In the present review, we summarize the recent data about the natural reservoir of non-baumannii Acinetobacter including the novel species that have been described for the first time from environmental sources and reported during the last years. PMID- 26870017 TI - Comparative Genomic Analysis of the ICESa2603 Family ICEs and Spread of erm(B)- and tet(O)-Carrying Transferable 89K-Subtype ICEs in Swine and Bovine Isolates in China. AB - Integrative and conjugative elements (ICEs) of the ICESa2603 family have been isolated from several species of Streptococcus spp.; however, the comparative genomic and evolutionary analyses of these particular ICEs are currently only at their initial stages. By investigating 13 ICEs of the ICESa2603 family and two ICESa2603 family-like ICEs derived from diverse hosts and locations, we have determined that ICEs comprised a backbone of 30 identical syntenic core genes and accessory genes that were restricted to the intergenic sites or the 3'-end of the non-conserved domain of core genes to maintain its function. ICESa2603 family integrase IntICE Sa 2603 specifically recognized a 15-bp att sequence (TTATTTAAGAGTAAC) at the 3'-end of rplL, which was highly conserved in genus Streptococcus. Phylogenetic analyses suggest that extensive recombination/insertion and the occurrence of a hybrid/mosaic in the ICESa2603 family were responsible for the significant increase in ICE diversity, thereby broadening its host range. Approximately 42.5 and 38.1% of the tested Streptococcus suis and Streptococcus agalactiae clinical isolates respectively contained ICESa2603 family Type IV secretion system (T4SS) genes, and 80.5 and 62.5% of which also respectively carried int ICE Sa 2603, indicating that ICESa2603 family is widely distributed across these bacteria. Sequencing and conjugation transfer of a novel sequence type ST303 clinical S. suis isolate HB1011 demonstrated that the 89K-subtype ICESsuHB1011 retained its transferrable function, thereby conferring tetracycline and macrolide resistance. PMID- 26870018 TI - Metagenomic Analysis Reveals Symbiotic Relationship among Bacteria in Microcystis Dominated Community. AB - Microcystis bloom, a cyanobacterial mass occurrence often found in eutrophicated water bodies, is one of the most serious threats to freshwater ecosystems worldwide. In nature, Microcystis forms aggregates or colonies that contain heterotrophic bacteria. The Microcystis-bacteria colonies were persistent even when they were maintained in lab culture for a long period. The relationship between Microcystis and the associated bacteria was investigated by a metagenomic approach in this study. We developed a visualization-guided method of binning for genome assembly after total colony DNA sequencing. We found that the method was effective in grouping sequences and it did not require reference genome sequence. Individual genomes of the colony bacteria were obtained and they provided valuable insights into microbial community structures. Analysis of metabolic pathways based on these genomes revealed that while all heterotrophic bacteria were dependent upon Microcystis for carbon and energy, Vitamin B12 biosynthesis, which is required for growth by Microcystis, was accomplished in a cooperative fashion among the bacteria. Our analysis also suggests that individual bacteria in the colony community contributed a complete pathway for degradation of benzoate, which is inhibitory to the cyanobacterial growth, and its ecological implication for Microcystis bloom is discussed. PMID- 26870019 TI - A Bacterial Quorum-Sensing Precursor Induces Mortality in the Marine Coccolithophore, Emiliania huxleyi. AB - Interactions between phytoplankton and bacteria play a central role in mediating biogeochemical cycling and food web structure in the ocean. However, deciphering the chemical drivers of these interspecies interactions remains challenging. Here, we report the isolation of 2-heptyl-4-quinolone (HHQ), released by Pseudoalteromonas piscicida, a marine gamma-proteobacteria previously reported to induce phytoplankton mortality through a hitherto unknown algicidal mechanism. HHQ functions as both an antibiotic and a bacterial signaling molecule in cell cell communication in clinical infection models. Co-culture of the bloom-forming coccolithophore, Emiliania huxleyi with both live P. piscicida and cell-free filtrates caused a significant decrease in algal growth. Investigations of the P. piscicida exometabolome revealed HHQ, at nanomolar concentrations, induced mortality in three strains of E. huxleyi. Mortality of E. huxleyi in response to HHQ occurred slowly, implying static growth rather than a singular loss event (e.g., rapid cell lysis). In contrast, the marine chlorophyte, Dunaliella tertiolecta and diatom, Phaeodactylum tricornutum were unaffected by HHQ exposures. These results suggest that HHQ mediates the type of inter-domain interactions that cause shifts in phytoplankton population dynamics. These chemically mediated interactions, and other like it, ultimately influence large scale oceanographic processes. PMID- 26870020 TI - Long-Term Oil Contamination Alters the Molecular Ecological Networks of Soil Microbial Functional Genes. AB - With knowledge on microbial composition and diversity, investigation of within community interactions is a further step to elucidate microbial ecological functions, such as the biodegradation of hazardous contaminants. In this work, microbial functional molecular ecological networks were studied in both contaminated and uncontaminated soils to determine the possible influences of oil contamination on microbial interactions and potential functions. Soil samples were obtained from an oil-exploring site located in South China, and the microbial functional genes were analyzed with GeoChip, a high-throughput functional microarray. By building random networks based on null model, we demonstrated that overall network structures and properties were significantly different between contaminated and uncontaminated soils (P < 0.001). Network connectivity, module numbers, and modularity were all reduced with contamination. Moreover, the topological roles of the genes (module hub and connectors) were altered with oil contamination. Subnetworks of genes involved in alkane and polycyclic aromatic hydrocarbon degradation were also constructed. Negative co occurrence patterns prevailed among functional genes, thereby indicating probable competition relationships. The potential "keystone" genes, defined as either "hubs" or genes with highest connectivities in the network, were further identified. The network constructed in this study predicted the potential effects of anthropogenic contamination on microbial community co-occurrence interactions. PMID- 26870016 TI - KSHV Genome Replication and Maintenance. AB - Kaposi's sarcoma associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is a major etiological agent for multiple severe malignancies in immune-compromised patients. KSHV establishes lifetime persistence in the infected individuals and displays two distinct life cycles, generally a prolonged passive latent, and a short productive or lytic cycle. During latent phase, the viral episome is tethered to the host chromosome and replicates once during every cell division. Latency-associated nuclear antigen (LANA) is a predominant multifunctional nuclear protein expressed during latency, which plays a central role in episome tethering, replication and perpetual segregation of the episomes during cell division. LANA binds cooperatively to LANA binding sites (LBS) within the terminal repeat (TR) region of the viral episome as well as to the cellular nucleosomal proteins to tether viral episome to the host chromosome. LANA has been shown to modulate multiple cellular signaling pathways and recruits various cellular proteins such as chromatin modifying enzymes, replication factors, transcription factors, and cellular mitotic framework to maintain a successful latent infection. Although, many other regions within the KSHV genome can initiate replication, KSHV TR is important for latent DNA replication and possible segregation of the replicated episomes. Binding of LANA to LBS favors the recruitment of various replication factors to initiate LANA dependent DNA replication. In this review, we discuss the molecular mechanisms relevant to KSHV genome replication, segregation, and maintenance of latency. PMID- 26870021 TI - Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance. AB - Darunavir (DRV) is one of the most powerful protease inhibitors (PIs) for treating human immunodeficiency virus type-1 (HIV-1) infection and presents a high genetic barrier to the generation of resistant viruses. However, DRV resistant HIV-1 infrequently emerges from viruses exhibiting resistance to other protease inhibitors. To address this resistance, researchers have gathered genetic information on DRV resistance. In contrast, few structural insights into the mechanism underlying DRV resistance are available. To elucidate this mechanism, we determined the crystal structure of the ligand-free state of a protease with high-level DRV resistance and six DRV resistance-associated mutations (including I47V and I50V), which we generated by in vitro selection. This crystal structure showed a unique curling conformation at the flap regions that was not found in the previously reported ligand-free protease structures. Molecular dynamics simulations indicated that the curled flap conformation altered the flap dynamics. These results suggest that the preference for a unique flap conformation influences DRV binding. These results provide new structural insights into elucidating the molecular mechanism of DRV resistance and aid to develop PIs effective against DRV-resistant viruses. PMID- 26870022 TI - The Cell Wall Protein Ecm33 of Candida albicans is Involved in Chronological Life Span, Morphogenesis, Cell Wall Regeneration, Stress Tolerance, and Host-Cell Interaction. AB - Ecm33 is a glycosylphosphatidylinositol-anchored protein in the human pathogen Candida albicans. This protein is known to be involved in fungal cell wall integrity (CWI) and is also critical for normal virulence in the mouse model of hematogenously disseminated candidiasis, but its function remains unknown. In this work, several phenotypic analyses of the C. albicans ecm33/ecm33 mutant (RML2U) were performed. We observed that RML2U displays the inability of protoplast to regenerate the cell wall, activation of the CWI pathway, hypersensitivity to temperature, osmotic and oxidative stresses and a shortened chronological lifespan. During the exponential and stationary culture phases, nuclear and actin staining revealed the possible arrest of the cell cycle in RML2U cells. Interestingly, a "veil growth," never previously described in C. albicans, was serendipitously observed under static stationary cells. The cells that formed this structure were also observed in cornmeal liquid cultures. These cells are giant, round cells, without DNA, and contain large vacuoles, similar to autophagic cells observed in other fungi. Furthermore, RML2U was phagocytozed more than the wild-type strain by macrophages at earlier time points, but the damage caused to the mouse cells was less than with the wild-type strain. Additionally, the percentage of RML2U apoptotic cells after interaction with macrophages was fewer than in the wild-type strain. PMID- 26870023 TI - Immune-Enhancing Effects of Taishan Pinus massoniana Pollen Polysaccharides on DNA Vaccine Expressing Bordetella avium ompA. AB - Bordetella avium is the causative agent of bordetellosis, which remains to be the cause of severe losses in the turkey industry. Given the lack of vaccines that can provide good protection, developing a novel vaccine against B. avium infection is crucial. In this study, we constructed a eukaryotic expression plasmid, which expressed the outer membrane protein A (ompA) of B. avium, to prepare a B. avium recombinant ompA-DNA vaccine. Three concentrations (low, middle, and high) of Taishan Pinus massoniana pollen polysaccharides (TPPPS), a known immunomodulator, were used as adjuvants, and their immune conditioning effects on the developed DNA vaccine were examined. The pure ompA-DNA vaccine, Freund's incomplete adjuvant ompA-DNA vaccine, and the empty plasmid served as the controls. The chickens in each group were separately inoculated with these vaccines three times at 1, 7, and 14 days old. Dynamic changes in antibody production, cytokine secretion, and lymphocyte count were then determined from 7 to 49 days after the first inoculation. Protective rates of the vaccines were also determined after the third inoculation. Results showed that the pure DNA vaccine obviously induced the production of antibodies, the secretion of cytokines, and the increase in CD(4+) and CD(8+) T lymphocyte counts in peripheral blood, as well as provided a protective rate of 50% to the B. avium challenged chickens. The chickens inoculated with the TPPPS adjuvant ompA-DNA vaccine and Freund's adjuvant ompA-DNA vaccine demonstrated higher levels of immune responses than those inoculated with pure ompA-DNA vaccine, whereas only the ompA-DNA vaccine with 200 mg/mL TPPPS completely protected the chickens against B. avium infection. These findings indicate that the B. avium ompA-DNA vaccine combined with TPPPS is a potentially effective B. avium vaccine. PMID- 26870024 TI - Applications of Bayesian Phylodynamic Methods in a Recent U.S. Porcine Reproductive and Respiratory Syndrome Virus Outbreak. AB - Classical phylogenetic methods such as neighbor-joining or maximum likelihood trees, provide limited inferences about the evolution of important pathogens and ignore important evolutionary parameters and uncertainties, which in turn limits decision making related to surveillance, control, and prevention resources. Bayesian phylodynamic models have recently been used to test research hypotheses related to evolution of infectious agents. However, few studies have attempted to model the evolutionary dynamics of porcine reproductive and respiratory syndrome virus (PRRSV) and, to the authors' knowledge, no attempt has been made to use large volumes of routinely collected data, sometimes referred to as big data, in the context of animal disease surveillance. The objective of this study was to explore and discuss the applications of Bayesian phylodynamic methods for modeling the evolution and spread of a notable 1-7-4 RFLP-type PRRSV between 2014 and 2015. A convenience sample of 288 ORF5 sequences was collected from 5 swine production systems in the United States between September 2003 and March 2015. Using coalescence and discrete trait phylodynamic models, we were able to infer population growth and demographic history of the virus, identified the most likely ancestral system (root state posterior probability = 0.95) and revealed significant dispersal routes (Bayes factor > 6) of viral exchange among systems. Results indicate that currently circulating viruses are evolving rapidly, and show a higher level of relative genetic diversity over time, when compared to earlier relatives. Biological soundness of model results is supported by the finding that sow farms were responsible for PRRSV spread within the systems. Such results cannot be obtained by traditional phylogenetic methods, and therefore, our results provide a methodological framework for molecular epidemiological modeling of new PRRSV outbreaks and demonstrate the prospects of phylodynamic models to inform decision-making processes for routine surveillance and, ultimately, to support prevention and control of food animal disease at local and regional scales. PMID- 26870026 TI - Cytotoxic Potential of Bacillus cereus Strains ATCC 11778 and 14579 Against Human Lung Epithelial Cells Under Microaerobic Growth Conditions. AB - Bacillus cereus, a food poisoning bacterium closely related to Bacillus anthracis, secretes a multitude of virulence factors including enterotoxins, hemolysins, and phospholipases. However, the majority of the in vitro experiments evaluating the cytotoxic potential of B. cereus were carried out in the conditions of aeration, and the impact of the oxygen limitation in conditions encountered by the microbe in natural environment such as gastrointestinal tract remains poorly understood. This research reports comparative analysis of ATCC strains 11778 (BC1) and 14579 (BC2) in aerobic and microaerobic (static) cultures with regard to their toxicity for human lung epithelial cells. We showed that BC1 increased its toxicity upon oxygen limitation while BC2 was highly cytotoxic in both growth conditions. The combined effect of the pore-forming, cholesterol dependent hemolysin, cereolysin O (CLO), and metabolic product(s) such as succinate produced in microaerobic conditions provided substantial contribution to the toxicity of BC1 but not BC2 which relied mainly on other toxins. This mechanism is shared between CB1 and B. anthracis. It involves the permeabilization of the cell membrane which facilitates transport of toxic bacterial metabolites into the cell. The toxicity of BC1 was potentiated in the presence of bovine serum albumin which appeared to serve as reservoir for bacteria-derived nitric oxide participating in the downstream production of reactive oxidizing species with the properties of peroxynitrite. In agreement with this the BC1 cultures demonstrated the increased oxidation of the indicator dye Amplex Red catalyzed by peroxidase as well as the increased toxicity in the presence of externally added ascorbic acid. PMID- 26870027 TI - Multilocus Sequence Typing and Antimicrobial Resistance of Campylobacter jejuni Isolated from Dairy Calves in Austria. AB - Human campylobacteriosis is primarily associated with poultry but also cattle. In this study, 55 Campylobacter jejuni strains isolated from 382 dairy calves' feces were differentiated by multilocus sequence typing and tested for antimicrobial resistance. The most prevalent sequence type (ST) was ST883 (20.0%), followed by ST48 (14.5%), and ST50 (9.1%). In contrast to ST48 and ST50, ST883 has rarely been described in cattle previously. Furthermore, risk factor analysis was performed for the presence of the most prevalent STs in these calves. Multiple regression analysis revealed that the type of farm (organic vs. conventional) and calf housing (place, and individual vs. group) were identified as significantly (p < 0.05) associated with the presence of ST883 in calves, and ST50 was associated with calf diarrhea. Antimicrobial resistance was detected in 58.2% of the isolates. Most of the resistant isolates (81.3%) were resistant to more than one antimicrobial. Most frequently, resistance to ciprofloxacin (49.1%), followed by nalidixic acid (42.8%), and tetracycline (14.5%) was observed. The results of the present study support the hypothesis that dairy calves may serve as a potential reservoir for C. jejuni and pose a risk for transmission, including antimicrobial resistant isolates to the environment and to humans. PMID- 26870029 TI - Radiolytic Hydrogen Production in the Subseafloor Basaltic Aquifer. AB - Hydrogen (H2) is produced in geological settings by dissociation of water due to radiation from radioactive decay of naturally occurring uranium ((238)U, (235)U), thorium ((232)Th) and potassium ((40)K). To quantify the potential significance of radiolytic H2 as an electron donor for microbes within the South Pacific subseafloor basaltic aquifer, we use radionuclide concentrations of 43 basalt samples from IODP Expedition 329 to calculate radiolytic H2 production rates in basement fractures. The samples are from three sites with very different basement ages and a wide range of alteration types. U, Th, and K concentrations vary by up to an order of magnitude from sample to sample at each site. Comparison of our samples to each other and to the results of previous studies of unaltered East Pacific Rise basalt suggests that significant variations in radionuclide concentrations are due to differences in initial (unaltered basalt) concentrations (which can vary between eruptive events) and post-emplacement alteration. However, there is no clear relationship between alteration type and calculated radiolytic yields. Local maxima in U, Th, and K produce hotspots of H2 production, causing calculated radiolytic rates to differ by up to a factor of 80 from sample to sample. Fracture width also greatly influences H2 production, where microfractures are hotspots for radiolytic H2 production. For example, H2 production rates normalized to water volume are 190 times higher in 1 MUm wide fractures than in fractures that are 10 cm wide. To assess the importance of water radiolysis for microbial communities in subseafloor basaltic aquifers, we compare electron transfer rates from radiolysis to rates from iron oxidation in subseafloor basalt. Radiolysis appears likely to be a more important electron donor source than iron oxidation in old (>10 Ma) basement basalt. Radiolytic H2 production in the volume of water adjacent to a square cm of the most radioactive SPG basalt may support as many as 1500 cells. PMID- 26870025 TI - Using "Omics" and Integrated Multi-Omics Approaches to Guide Probiotic Selection to Mitigate Chytridiomycosis and Other Emerging Infectious Diseases. AB - Emerging infectious diseases in wildlife are responsible for massive population declines. In amphibians, chytridiomycosis caused by Batrachochytrium dendrobatidis, Bd, has severely affected many amphibian populations and species around the world. One promising management strategy is probiotic bioaugmentation of antifungal bacteria on amphibian skin. In vivo experimental trials using bioaugmentation strategies have had mixed results, and therefore a more informed strategy is needed to select successful probiotic candidates. Metagenomic, transcriptomic, and metabolomic methods, colloquially called "omics," are approaches that can better inform probiotic selection and optimize selection protocols. The integration of multiple omic data using bioinformatic and statistical tools and in silico models that link bacterial community structure with bacterial defensive function can allow the identification of species involved in pathogen inhibition. We recommend using 16S rRNA gene amplicon sequencing and methods such as indicator species analysis, the Kolmogorov-Smirnov Measure, and co-occurrence networks to identify bacteria that are associated with pathogen resistance in field surveys and experimental trials. In addition to 16S amplicon sequencing, we recommend approaches that give insight into symbiont function such as shotgun metagenomics, metatranscriptomics, or metabolomics to maximize the probability of finding effective probiotic candidates, which can then be isolated in culture and tested in persistence and clinical trials. An effective mitigation strategy to ameliorate chytridiomycosis and other emerging infectious diseases is necessary; the advancement of omic methods and the integration of multiple omic data provide a promising avenue toward conservation of imperiled species. PMID- 26870028 TI - Antibodies Against Glycolipids Enhance Antifungal Activity of Macrophages and Reduce Fungal Burden After Infection with Paracoccidioides brasiliensis. AB - Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs) from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-gamma and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P. brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P. brasiliensis adding to other well-studied mediators of the immune response to this fungus. PMID- 26870030 TI - Integrated Translatomics with Proteomics to Identify Novel Iron-Transporting Proteins in Streptococcus pneumoniae. AB - Streptococcus pneumoniae (S.pneumoniae) is a major human pathogen causing morbidity and mortality worldwide. Efficiently acquiring iron from the environment is critical for S. pneumoniae to sustain growth and cause infection. There are only three known iron-uptake systems in Streptococcal species responsible for iron acquisition from the host, including ABC transporters PiaABC, PiuABC, and PitABC. Besides, no other iron-transporting system has been suggested. In this work, we employed our newly established translating mRNA analysis integrated with proteomics to evaluate the possible existence of novel iron transporters in the bacterium. We simultaneously deleted the iron-binding protein genes of the three iron-uptake systems to construct a piaA/piuA/pitA triple mutant (Tri-Mut) of S. pneumoniae D39, in which genes and proteins related to iron transport should be regulated in response to the deletion. With ribosome associated mRNA sequencing-based translatomics focusing on translating mRNA and iTRAQ quantitative proteomics based on the covalent labeling of peptides with tags of varying mass, we indeed observed a large number of genes and proteins representing various coordinated biological pathways with significantly altered expression levels in the Tri-Mut mutant. Highlighted in this observation is the identification of several new potential iron-uptake ABC transporters participating in iron metabolism of Streptococcus. In particular, putative protein SPD_1609 in operon 804 was verified to be a novel iron-binding protein with similar function to PitA in S. pneumoniae. These data derived from the integrative translatomics and proteomics analyses provided rich information and insightful clues for further investigations on iron-transporting mechanism in bacteria and the interplay between Streptococcal iron availability and the biological metabolic pathways. PMID- 26870032 TI - De Novo Analysis of Wolfiporia cocos Transcriptome to Reveal the Differentially Expressed Carbohydrate-Active Enzymes (CAZymes) Genes During the Early Stage of Sclerotial Growth. AB - The sclerotium of Wolfiporia cocos has been used as an edible mushroom and/or a traditional herbal medicine for centuries. W. cocos sclerotial formation is dependent on parasitism of the wood of Pinus species. Currently, the sclerotial development mechanisms of W. cocos remain largely unknown and the lack of pine resources limit the commercial production. The CAZymes (carbohydrate-active enzymes) play important roles in degradation of the plant cell wall to provide carbohydrates for fungal growth, development, and reproduction. In this study, the transcript profiles from W. cocos mycelium and 2-months-old sclerotium, the early stage of sclerotial growth, were specially analyzed using de novo sequencing technology. A total of 142,428,180 high-quality reads of mycelium and 70,594,319 high-quality reads of 2-months-old sclerotium were obtained. Additionally, differentially expressed genes from the W. cocos mycelium and 2 months-old sclerotium stages were analyzed, resulting in identification of 69 CAZymes genes which were significantly up-regulated during the early stage of sclerotial growth compared to that of in mycelium stage, and more than half of them belonged to glycosyl hydrolases (GHs) family, indicating the importance of W. cocos GHs family for degrading the pine woods. And qRT-PCR was further used to confirm the expression pattern of these up-regulated CAZymes genes. Our results will provide comprehensive CAZymes genes expression information during W. cocos sclerotial growth at the transcriptional level and will lay a foundation for functional genes studies in this fungus. In addition, our study will also facilitate the efficient use of limited pine resources, which is significant for promoting steady development of Chinese W. cocos industry. PMID- 26870033 TI - Future Applications of Biotechnology to the Energy Industry. PMID- 26870031 TI - Using the Ferret as an Animal Model for Investigating Influenza Antiviral Effectiveness. AB - The concern of the emergence of a pandemic influenza virus has sparked an increased effort toward the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titer of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness. PMID- 26870034 TI - Antiglutamate Receptor Antibodies and Cognitive Impairment in Primary Antiphospholipid Syndrome and Systemic Lupus Erythematosus. AB - Systemic lupus erythematosus (SLE) and antiphospholipid syndrome have an increased risk to develop cognitive impairment. A possible role for antiphospholipid antibodies (aPL) and antiglutamate receptor (anti-NMDA) antibodies in the pathogenesis of neurological manifestations of these two conditions, have been suggested. In particular, the role of anti-NMDA antibodies in the pathogenesis of neuropsychiatric SLE is supported by several experimental studies in animal models and by the finding of a correlation between anti-NMDA positivity in cerebrospinal fluid and neurological manifestations of SLE. However, data from the literature are controversial, as several studies have reported a correlation of these antibodies with mild cognitive impairment in SLE, but more recent studies have not confirmed this finding. The synergism between anti-NMDA and other concomitant autoantibodies, such as aPL, can be hypothesized to play a role in inducing the tissue damage and eventually the functional abnormalities. In line with this hypothesis, we have found a high incidence of at least one impaired cognitive domain in a small cohort of patients with primary APS (PAPS) and SLE. Interestingly, aPL were associated with low scoring for language ability and attention while anti-NMDA titers and mini-mental state examination scoring were inversely correlated. However, when patients were stratified according to the presence/absence of aPL, the correlation was confirmed in aPL positive patients only. Should those findings be confirmed, the etiology of the prevalent defects found in PAPS patients as well as the synergism between aPL and anti-NMDA antibodies would need to be explored. PMID- 26870035 TI - Cytokines Induce Faster Membrane Diffusion of MHC Class I and the Ly49A Receptor in a Subpopulation of Natural Killer Cells. AB - Cytokines have the potential to drastically augment immune cell activity. Apart from altering the expression of a multitude of proteins, cytokines also affect immune cell dynamics. However, how cytokines affect the molecular dynamics within the cell membrane of immune cells has not been addressed previously. Molecular movement is a vital component of all biological processes, and the rate of motion is, thus, an inherent determining factor for the pace of such processes. Natural killer (NK) cells are cytotoxic lymphocytes, which belong to the innate immune system. By fluorescence correlation spectroscopy, we investigated the influence of cytokine stimulation on the membrane density and molecular dynamics of the inhibitory receptor Ly49A and its ligand, the major histocompatibility complex class I allele H-2D(d), in freshly isolated murine NK cells. H-2D(d) was densely expressed and diffused slowly in resting NK cells. Ly49A was expressed at a lower density and diffused faster. The diffusion rate in resting cells was not altered by disrupting the actin cytoskeleton. A short-term stimulation with interleukin-2 or interferon-alpha + beta did not change the surface density of moving H-2D(d) or Ly49A, despite a slight upregulation at the cellular level of H-2D(d) by interferon-alpha + beta, and of Ly49A by IL-2. However, the molecular diffusion rates of both H-2D(d) and Ly49A increased significantly. A multivariate analysis revealed that the increased diffusion was especially marked in a subpopulation of NK cells, where the diffusion rate was increased around fourfold compared to resting NK cells. After IL-2 stimulation, this subpopulation of NK cells also displayed lower density of Ly49A and higher brightness per entity, indicating that Ly49A may homo-cluster to a larger extent in these cells. A faster diffusion of inhibitory receptors could enable a faster accumulation of these molecules at the immune synapse with a target cell, eventually leading to a more efficient NK cell response. It has previously been assumed that cytokines regulate immune cells primarily via alterations of protein expression levels or posttranslational modifications. These findings suggest that cytokines may also modulate immune cell efficiency by increasing the molecular dynamics early on in the response. PMID- 26870036 TI - T Cells and Cancer: How Metabolism Shapes Immunity. AB - Tumor microenvironment is characterized by a consistent reduction in oxygen and blood-borne nutrients that significantly affects the metabolism of distinct cell subsets. Immune cells populating malignant lesions need to activate alternative pathways to overcome tumor-prolonged nutrient deprivation. In particular, the metabolic switch occurring in transforming tissues dramatically impacts on tumor infiltrating T cell biology. Remarkably, the recruitment and activation of T cell within cancers are instrumental for effective antitumor response. Therefore, T cell metabolic adaptation acts as crucial checkpoint hijacked by tumors to dampen antitumor immunity. PMID- 26870037 TI - Immunogenicity to Biotherapeutics - The Role of Anti-drug Immune Complexes. AB - Biological molecules are increasingly becoming a part of the therapeutics portfolio that has been either recently approved for marketing or those that are in the pipeline of several biotech and pharmaceutical companies. This is largely based on their ability to be highly specific relative to small molecules. However, by virtue of being a large protein, and having a complex structure with structural variability arising from production using recombinant gene technology in cell lines, such therapeutics run the risk of being recognized as foreign by a host immune system. In the context of immune-mediated adverse effects that have been documented to biological drugs thus far, including infusion reactions, and the evolving therapeutic platforms in the pipeline that engineer different functional modules in a biotherapeutic, it is critical to understand the interplay of the adaptive and innate immune responses, the pathophysiology of immunogenicity to biological drugs in instances where there have been immune mediated adverse clinical sequelae and address technical approaches for their laboratory evaluation. The current paradigm in immunogenicity evaluation has a tiered approach to the detection and characterization of anti-drug antibodies (ADAs) elicited in vivo to a biotherapeutic; alongside with the structural, biophysical, and molecular information of the therapeutic, these analytical assessments form the core of the immunogenicity risk assessment. However, many of the immune-mediated adverse effects attributed to ADAs require the formation of a drug/ADA immune complex (IC) intermediate that can have a variety of downstream effects. This review will focus on the activation of potential immunopathological pathways arising as a consequence of circulating as well as cell surface bound drug bearing ICs, risk factors that are intrinsic either to the therapeutic molecule or to the host that might predispose to IC-mediated effects, and review the recent literature on prevalence and intensity of established examples of type II and III hypersensitivity reactions that follow the administration of a biotherapeutic. Additionally, we propose methods for the study of immune parameters specific to the biology of ICs that could be of use in conjunction with the detection of ADAs in circulation. PMID- 26870038 TI - Expression of TLR-7, MyD88, NF-kB, and INF-alpha in B Lymphocytes of Mayan Women with Systemic Lupus Erythematosus in Mexico. AB - BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease involving multiple organs. It is currently accepted that several genetic, environmental, and hormonal factors are contributing to its development. Innate immunity may have a great influence in autoimmunity through Toll-like receptors. TLR-7 recognizing single-strand RNA has been involved in SLE. Its activation induces intracellular signal with attraction of MyD88 and NF kBp65, leading to IFN-alpha synthesis which correlate with disease activity. OBJECTIVE: To assess the expression of TLR-7, MyD88, and NF-kBp65 in B lymphocytes of Mayan women with SLE. METHODS: One hundred patients with SLE and 100 healthy controls, all of them Mayan women, were included. TLR-7 was analyzed on B and T lymphocytes, and MyD88 and NF-kB only in B lymphocytes. Serum INF alpha level was evaluated by ELISA. RESULTS: Significant expression (p < 0.0001) of TLR-7 in B and T lymphocytes and serum IFN-alpha increased (p = 0.034) was observed in patients. MyD88 and NF-kBp65 were also increased in B lymphocytes of patients. TLR-7 and NF-kBp65 expression correlated, but no correlation with INF alpha and disease activity was detected. CONCLUSION: Data support the role of TLR 7 and signal proteins in the pathogenesis of SLE in the Mayan population of Yucatan. PMID- 26870042 TI - Editorial: Searching for Immune Tolerance Manipulating New Molecules and Exploiting New Concepts on Lymphocyte Biology. PMID- 26870041 TI - B Cells Negatively Regulate the Establishment of CD49b(+)T-bet(+) Resting Memory T Helper Cells in the Bone Marrow. AB - During an immune reaction, some antigen-experienced CD4 T cells relocate from secondary lymphoid organs (SLOs) to the bone marrow (BM) in a CD49b-dependent manner and reside and rest there as professional memory CD4 T cells. However, it remains unclear how the precursors of BM memory CD4 T cells are generated in the SLOs. While several studies have so far shown that B cell depletion reduces the persistence of memory CD4 T cells in the spleen, we here show that B cell depletion enhances the establishment of memory CD4 T cells in the BM and that B cell transfer conversely suppresses it. Interestingly, the number of antigen experienced CD4 T cells in the BM synchronizes the number of CD49b(+)T-bet(+) antigen-experienced CD4 T cells in the spleen. CD49b(+)T-bet(+) antigen experienced CD4 T cells preferentially localize in the red pulp area of the spleen and the BM in a T-bet-independent manner. We suggest that B cells negatively control the generation of CD49b(+)T-bet(+) precursors of resting memory CD4 T cells in the spleen and may play a role in bifurcation of activated effector and resting memory CD4 T cell lineages. PMID- 26870043 TI - GPR41 and GPR43 in Obesity and Inflammation - Protective or Causative? AB - GPR41 and GPR43 are a pair of mammalian G protein-coupled receptors (GPCRs) expressed in human adipocytes, colon epithelial cells, and peripheral blood mononuclear cells. These receptors are activated by short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate - which are produced during dietary fiber fermentation by resident gut bacteria. This unique ligand specificity suggests that GPR41 and GPR43 may mediate the interaction between the human host and the gut microbiome. Indeed, studies on knockout mice implicate GPR41 and GPR43 in chronic inflammatory disorders such as obesity, colitis, asthma and arthritis. However, whether GPR41 and GPR43 are protective or causative is inconsistent between studies. This discrepancy may be due to differences in the disease models used, the inbred mouse strains, or non-specific knockout effects. Here, we review the latest findings on GPR41 and GPR43, highlighting contradictory observations. With GPR41 and GPR43 being considered as drug targets, it is pertinent that their role is fully elucidated. We propose that future studies on human tissues, ex vivo, may allow us to confirm the role of GPR41 and GPR43 in humans, be it protective or causative. PMID- 26870039 TI - Staphylococcal Superantigens Spark Host-Mediated Danger Signals. AB - Staphylococcal enterotoxin B (SEB) of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific Vbeta regions of T-cell receptors (TCR) and major histocompatibility complex (MHC) class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes/macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor alpha, interleukin 1 (IL-1), IL-2, interferon gamma (IFNgamma), and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. Because of superantigen-induced T cells skewed toward TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR/MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFkappaB and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an "SEB-only" model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA/RNA sensors, apoptosis/DNA damage-related molecules, immunoproteasome components, as well as antiviral and IFN-stimulated genes. The host-wide induction of these, and other, antimicrobial defense genes provide evidence that SEB elicits danger signals resulting in multi-organ damage and toxic shock. Ultimately, these discoveries might lead to novel therapeutics for various superantigen-based diseases. PMID- 26870044 TI - The Challenge and Potential of Metagenomics in the Clinic. AB - The bacteria, fungi, and viruses that live on and in us have a tremendous impact on our day-to-day health and are often linked to many diseases, including autoimmune disorders and infections. Diagnosing and treating these disorders relies on accurate identification and characterization of the microbial community. Current sequencing technologies allow the sequencing of the entire nucleic acid complement of a sample providing an accurate snapshot of the community members present in addition to the full genetic potential of that microbial community. There are a number of clinical applications that stand to benefit from these data sets, such as the rapid identification of pathogens present in a sample. Other applications include the identification of antibiotic resistance genes, diagnosis and treatment of gastrointestinal disorders, and many other diseases associated with bacterial, viral, and fungal microbiomes. Metagenomics also allows the physician to probe more complex phenotypes such as microbial dysbiosis with intestinal disorders and disruptions of the skin microbiome that may be associated with skin disorders. Many of these disorders are not associated with a single pathogen but emerge as a result of complex ecological interactions within microbiota. Currently, we understand very little about these complex phenotypes, yet clearly they are important and in some cases, as with fecal microbiota transplants in Clostridium difficile infections, treating the microbiome of the patient is effective. Here, we give an overview of metagenomics and discuss a number of areas where metagenomics is applicable in the clinic, and progress being made in these areas. This includes (1) the identification of unknown pathogens, and those pathogens particularly hard to culture, (2) utilizing functional information and gene content to understand complex infections such as Clostridium difficile, and (3) predicting antimicrobial resistance of the community using genetic determinants of resistance identified from the sequencing data. All of these applications rely on sophisticated computational tools, and we also discuss the importance of skilled bioinformatic support for the implementation and use of metagenomics in the clinic. PMID- 26870040 TI - Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition. AB - B7 proteins CD80 (B7-1) and CD86 (B7-2) are expressed on most antigen-presenting cells and provide critical co-stimulatory or inhibitory input to T cells via their T-cell-expressed receptors: CD28 and CTLA-4. CD28 is expressed on effector T cells and regulatory T cells (Tregs), and CD28-dependent signals are required for optimum activation of effector T cell functions. CD28 ligation on effector T cells leads to formation of distinct molecular patterns and induction of cytoskeletal rearrangements at the immunological synapse (IS). CD28 plays a critical role in recruitment of protein kinase C (PKC)-theta to the effector T cell IS. CTLA-4 is constitutively expressed on the surface of Tregs, but it is expressed on effector T cells only after activation. As CTLA-4 binds to B7 proteins with significantly higher affinity than CD28, B7 ligand recognition by cells expressing both receptors leads to displacement of CD28 and PKC-theta from the IS. In Tregs, B7 ligand recognition leads to recruitment of CTLA-4 and PKC eta to the IS. CTLA-4 plays a role in regulation of T effector and Treg IS stability and cell motility. Due to their important roles in regulating T-cell mediated responses, B7 receptors are emerging as important drug targets in oncology. In this review, we present an integrated summary of current knowledge about the role of B7 family receptor-ligand interactions in the regulation of spatial and temporal IS dynamics in effector and Tregs. PMID- 26870046 TI - Genome-Wide Identification and Comparative Analysis of Cytosine-5 DNA Methyltransferase and Demethylase Families in Wild and Cultivated Peanut. AB - DNA methylation plays important roles in genome protection, regulation of gene expression and is associated with plants development. Plant DNA methylation pattern was mediated by cytosine-5 DNA methyltransferase and demethylase. Although the genomes of AA and BB wild peanuts have been fully sequenced, these two gene families have not been studied. In this study we report the identification and analysis of putative cytosine-5 DNA methyltransferases (C5 MTases) and demethylases in AA and BB wild peanuts. Cytosine-5 DNA methyltransferases in AA and BB wild peanuts could be classified in MET, CMT, and DRM2 groups based on their domain organization. This result was supported by the gene and protein structural characteristics and phylogenetic analysis. We found that some wild peanut DRM2 members didn't contain UBA domain which was different from other plants such as Arabidopsis, maize and soybean. Five DNA demethylase encoding genes were found in AA genome and five in BB genome. The selective pressure analysis showed that wild peanut C5-MTase genes mainly underwent purifying selection but many positive selection sites can be detected. Conversely, DNA demethylase genes mainly underwent positive selection during evolution. Additionally, the expression dynamic of cytosine-5 DNA methyltransferase and demethylase genes in different cultivated peanut tissues were analyzed. Expression result showed that cold, heat or PEG stress could influence the expression level of C5-MTase and DNA demethylase genes in cultivated peanut. These results are useful for better understanding the complexity of these two gene families, and will facilitate epigenetic studies in peanut in the future. PMID- 26870045 TI - Alloantibody Generation and Effector Function Following Sensitization to Human Leukocyte Antigen. AB - Allorecognition is the activation of the adaptive immune system to foreign human leukocyte antigen (HLA) resulting in the generation of alloantibodies. Due to a high polymorphism, foreign HLA is recognized by the immune system following transplant, transfusion, or pregnancy resulting in the formation of the germinal center and the generation of long-lived alloantibody-producing memory B cells. Alloantibodies recognize antigenic epitopes displayed by the HLA molecule on the transplanted allograft and contribute to graft damage through multiple mechanisms, including (1) activation of the complement cascade resulting in the formation of the MAC complex and inflammatory anaphylatoxins, (2) transduction of intracellular signals leading to cytoskeletal rearrangement, growth, and proliferation of graft vasculature, and (3) immune cell infiltration into the allograft via FcgammaR interactions with the FC portion of the antibody. This review focuses on the generation of HLA alloantibody, routes of sensitization, alloantibody specificity, and mechanisms of antibody-mediated graft damage. PMID- 26870047 TI - Global Analysis of WRKY Genes and Their Response to Dehydration and Salt Stress in Soybean. AB - WRKY proteins are plant specific transcription factors involved in various developmental and physiological processes, especially in biotic and abiotic stress resistance. Although previous studies suggested that WRKY proteins in soybean (Glycine max var. Williams 82) involved in both abiotic and biotic stress responses, the global information of WRKY proteins in the latest version of soybean genome (Wm82.a2v1) and their response to dehydration and salt stress have not been reported. In this study, we identified 176 GmWRKY proteins from soybean Wm82.a2v1 genome. These proteins could be classified into three groups, namely group I (32 proteins), group II (120 proteins), and group III (24 proteins). Our results showed that most GmWRKY genes were located on Chromosome 6, while chromosome 11, 12, and 20 contained the least number of this gene family. More GmWRKY genes were distributed on the ends of chromosomes to compare with other regions. The cis-acting elements analysis suggested that GmWRKY genes were transcriptionally regulated upon dehydration and salt stress. RNA-seq data analysis indicated that three GmWRKY genes responded negatively to dehydration, and 12 genes positively responded to salt stress at 1, 6, and 12 h, respectively. We confirmed by qRT-PCR that the expression of GmWRKY47 and GmWRKY 58 genes was decreased upon dehydration, and the expression of GmWRKY92, 144 and 165 genes was increased under salt treatment. PMID- 26870048 TI - Specific and Efficient Targeting of Cyanobacterial Bicarbonate Transporters to the Inner Envelope Membrane of Chloroplasts in Arabidopsis. AB - Installation of cyanobacterial bicarbonate transporters to the inner envelope membrane (IEM) of chloroplasts in C3 plants has been thought to improve photosynthetic performance. However, the method to deliver cyanobacterial bicarbonate transporters to the chloroplast IEM remains to be established. In this study, we provide evidence that the cyanobacterial bicarbonate transporters, BicA and SbtA, can be specifically installed into the chloroplast IEM using the chloroplast IEM targeting signal in conjunction with the transit peptide. We fused the transit peptide and the mature portion of Cor413im1, whose targeting mechanism to the IEM has been characterized in detail, to either BicA or SbtA isolated from Synechocystis sp. PCC6803. Among the seven chimeric constructs tested, we confirmed that four chimeric bicarbonate transporters, designated as BicAI, BicAII, SbtAII, and SbtAIII, were expressed in Arabidopsis. Furthermore, these chimeric transporters were specifically targeted to the chloroplast IEM. They were also resistant to alkaline extraction but can be solubilized by Triton X-100, indicating that they are integral membrane proteins in the chloroplast IEM. One of the transporters, BicA, could reside in the chloroplast IEM even after removal of the IEM targeting signal. Taken together, our results indicate that the addition of IEM targeting signal, as well as the transit peptide, to bicarbonate transporters allows us to efficiently target nuclear-encoded chimeric bicarbonate transporters to the chloroplast IEM. PMID- 26870049 TI - Cannabis sativa: The Plant of the Thousand and One Molecules. AB - Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times. This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers. Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively. In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes. Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities. The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data. Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures. Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories. Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented. PMID- 26870050 TI - Genome-Wide Identification and Expression Analysis of Homeodomain Leucine Zipper Subfamily IV (HDZ IV) Gene Family from Musa accuminata. AB - The homeodomain zipper family (HD-ZIP) of transcription factors is present only in plants and plays important role in the regulation of plant-specific processes. The subfamily IV of HDZ transcription factors (HD-ZIP IV) has primarily been implicated in the regulation of epidermal structure development. Though this gene family is present in all lineages of land plants, members of this gene family have not been identified in banana, which is one of the major staple fruit crops. In the present work, we identified 21 HDZIV encoding genes in banana by the computational analysis of banana genome resource. Our analysis suggested that these genes putatively encode proteins having all the characteristic domains of HDZIV transcription factors. The phylogenetic analysis of the banana HDZIV family genes further confirmed that after separation from a common ancestor, the banana, and poales lineages might have followed distinct evolutionary paths. Further, we conclude that segmental duplication played a major role in the evolution of banana HDZIV encoding genes. All the identified banana HDZIV genes expresses in different banana tissue, however at varying levels. The transcript levels of some of the banana HDZIV genes were also detected in banana fruit pulp, suggesting their putative role in fruit attributes. A large number of genes of this family showed modulated expression under drought and salinity stress. Taken together, the present work lays a foundation for elucidation of functional aspects of the banana HDZIV encoding genes and for their possible use in the banana improvement programs. PMID- 26870051 TI - Characterizing Variation of Branch Angle and Genome-Wide Association Mapping in Rapeseed (Brassica napus L.). AB - Changes in the rapeseed branch angle alter plant architecture, allowing more efficient light capture as planting density increases. In this study, a natural population of rapeseed was grown in three environments and evaluated for branch angle trait to characterize their phenotypic patterns and genotype with a 60K Brassica Infinium SNP array. Significant phenotypic variation was observed from 20 to 70 degrees . As a result, 25 significant quantitative trait loci (QTL) associated with branch angle were identified on chromosomes A2, A3, A7, C3, C5, and C7 by the MLM model in TASSEL 4.0. Orthologs of the functional candidate genes involved in branch angle were identified. Among the key QTL, the peak SNPs were close to the key orthologous genes BnaA.Lazy1 and BnaC.Lazy1 on A3 and C3 homologous genome blocks. With the exception of Lazy (LA) orthologous genes, SQUMOSA PROMOTER BINDING PROTEIN LIKE 14 (SPL14) and an auxin-responsive GRETCHEN HAGEN 3 (GH3) genes from Arabidopsis thaliana were identified close to two clusters of SNPs on the A7 and C7 chromosomes. These findings on multiple novel loci and candidate genes of branch angle will be useful for further understanding and genetic improvement of plant architecture in rapeseed. PMID- 26870053 TI - Identification of MicroRNAs and Their Targets Associated with Fruit-Bagging and Subsequent Sunlight Re-exposure in the "Granny Smith" Apple Exocarp Using High Throughput Sequencing. AB - Bagged fruits of green apple cultivar "Granny Smith" have been found to turn cardinal red after debagging during fruit-ripening in the Loess Plateau region of China. To understand this phenomenon at post-transcriptional level, we have investigated the roles of microRNAs (miRNAs) in response to debagging. Three small RNA libraries were primarily constructed from peels of "Granny Smith" apples subjected to bagging followed by sunlight re-exposure treatments (0, 6 h, 1 day) (debagging), and from peels of apples without any bagging treatments (0, 6 h, 1 day). 201 known miRNAs belonging to 43 miRNA families and 220 novel miRNAs were identified via high-throughput sequencing. Some miRNAs were found to be differentially expressed after debagging, which indicated that miRNAs affected anthocyanin accumulation through their target genes in mature apple. To further explore the effect of debagging on miRNAs regulating the expression of anthocyanin regulatory genes, four miRNAs and their target genes regulating anthocyanin accumulation, miR156, miR828, miR858, and miR5072, were compared between green cultivar "Granny Smith" and red cultivar "Starkrimson." Results showed that mdm-miR828 and mdm-miR858 regulated anthocyanin contents in both apple cultivars, while mdm-miR156 only affected anthocyanin accumulation in "Granny Smith," and miR5072 affected anthocyanin accumulation in "Starkrimson." Additional analysis of gene ontology for the differentially expressed miRNAs after debagging treatments and their predicted target genes showed that they were involved in photo-protective response after debagging from 0 h to 1 day; they might play important roles in fruit development and adaptation to high light stress. PMID- 26870052 TI - Ethylene and Metal Stress: Small Molecule, Big Impact. AB - The phytohormone ethylene is known to mediate a diverse array of signaling processes during abiotic stress in plants. Whereas many reports have demonstrated enhanced ethylene production in metal-exposed plants, the underlying molecular mechanisms are only recently investigated. Increasing evidence supports a role for ethylene in the regulation of plant metal stress responses. Moreover, crosstalk appears to exist between ethylene and the cellular redox balance, nutrients and other phytohormones. This review highlights our current understanding of the key role ethylene plays during responses to metal exposure. Moreover, particular attention is paid to the integration of ethylene within the broad network of plant responses to metal stress. PMID- 26870054 TI - Nitrogen Source and External Medium pH Interaction Differentially Affects Root and Shoot Metabolism in Arabidopsis. AB - Ammonium nutrition often represents an important growth-limiting stress in plants. Some of the symptoms that plants present under ammonium nutrition have been associated with pH deregulation, in fact external medium pH control is known to improve plants ammonium tolerance. However, the way plant cell metabolism adjusts to these changes is not completely understood. Thus, in this work we focused on how Arabidopsis thaliana shoot and root respond to different nutritional regimes by varying the nitrogen source ([Formula: see text] and [Formula: see text]), concentration (2 and 10 mM) and pH of the external medium (5.7 and 6.7) to gain a deeper understanding of cell metabolic adaptation upon altering these environmental factors. The results obtained evidence changes in the response of ammonium assimilation machinery and of the anaplerotic enzymes associated to Tricarboxylic Acids (TCA) cycle in function of the plant organ, the nitrogen source and the degree of ammonium stress. A greater stress severity at pH 5.7 was related to [Formula: see text] accumulation; this could not be circumvented in spite of the stimulation of glutamine synthetase, glutamate dehydrogenase, and TCA cycle anaplerotic enzymes. Moreover, this study suggests specific functions for different gln and gdh isoforms based on the nutritional regime. Overall, [Formula: see text] accumulation triggering ammonium stress appears to bear no relation to nitrogen assimilation impairment. PMID- 26870057 TI - Characterization of Silver Nanoparticles Internalized by Arabidopsis Plants Using Single Particle ICP-MS Analysis. AB - Plants act as a crucial interface between humans and their environment. The wide use of nanoparticles (NPs) has raised great concerns about their potential impacts on crop health and food safety, leading to an emerging research theme about the interaction between plants and NPs. However, up to this day even the basic issues concerning the eventual fate and characteristics of NPs after internalization are not clearly delineated due to the lack of a well-established technique for the quantitative analysis of NPs in plant tissues. We endeavored to combine a quantitative approach for NP analysis in plant tissues with TEM to localize the NPs. After using an enzymatic digestion to release the NPs from plant matrices, single particle-inductively coupled plasma-mass spectrometry (SP ICP-MS) is employed to determine the size distribution of silver nanoparticles (Ag NPs) in tissues of the model plant Arabidopsis thaliana after exposure to 10 nm Ag NPs. Our results show that Macerozyme R-10 treatment can release Ag NPs from Arabidopsis plants without changing the size of Ag NPs. The characteristics of Ag NPs obtained by SP-ICP-MS in both roots and shoots are in agreement with our transmission electron micrographs, demonstrating that the combination of an enzymatic digestion procedure with SP-ICP-MS is a powerful technique for quantitative determination of NPs in plant tissues. Our data reveal that Ag NPs tend to accumulate predominantly in the apoplast of root tissues whereby a minor portion is transported to shoot tissues. Furthermore, the fact that the measured size distribution of Ag NPs in plant tissue is centered at around 20.70 nm, which is larger than the initial 12.84 nm NP diameter, strongly implies that many internalized Ag NPs do not exist as intact individual particles anymore but are aggregated and/or biotransformed in the plant instead. PMID- 26870056 TI - Changes in the Proteome of Xylem Sap in Brassica oleracea in Response to Fusarium oxysporum Stress. AB - Fusarium oxysporum f.sp. conlutinans (Foc) is a serious root-invading and xylem colonizing fungus that causes yellowing in Brassica oleracea. To comprehensively understand the interaction between F. oxysporum and B. oleracea, composition of the xylem sap proteome of the non-infected and Foc-infected plants was investigated in both resistant and susceptible cultivars using liquid chromatography-tandem mass spectrometry (LC-MS/MS) after in-solution digestion of xylem sap proteins. Whole genome sequencing of Foc was carried out and generated a predicted Foc protein database. The predicted Foc protein database was then combined with the public B. oleracea and B. rapa protein databases downloaded from Uniprot and used for protein identification. About 200 plant proteins were identified in the xylem sap of susceptible and resistant plants. Comparison between the non-infected and Foc-infected samples revealed that Foc infection causes changes to the protein composition in B. oleracea xylem sap where repressed proteins accounted for a greater proportion than those of induced in both the susceptible and resistant reactions. The analysis on the proteins with concentration change > = 2-fold indicated a large portion of up- and down regulated proteins were those acting on carbohydrates. Proteins with leucine-rich repeats and legume lectin domains were mainly induced in both resistant and susceptible system, so was the case of thaumatins. Twenty-five Foc proteins were identified in the infected xylem sap and 10 of them were cysteine-containing secreted small proteins that are good candidates for virulence and/or avirulence effectors. The findings of differential response of protein contents in the xylem sap between the non-infected and Foc-infected samples as well as the Foc candidate effectors secreted in xylem provide valuable insights into B. oleracea Foc interactions. PMID- 26870055 TI - Creating Completely Both Male and Female Sterile Plants by Specifically Ablating Microspore and Megaspore Mother Cells. AB - Although genetically modified (GM) plants have improved commercially important traits, such as biomass and biofuel production, digestibility, bioremediation, ornamental value, and tolerance to biotic and abiotic stresses, there remain economic, political, or social concerns over potential ecological effects of transgene flow from GM plants. The current solution for preventing transgene flow from GM plants is genetically engineering sterility; however, approaches to generating both male and female sterility are limited. In addition, existing strategies for creating sterility lead to loss or modifications of entire flowers or floral organs. Here, we demonstrate that instead of the 1.5-kb promoter, the entire SOLO DANCERS (SDS) gene is required for its meiocyte-specific expression. We then developed an efficient method to specifically ablate microspore and megaspore mother cells using the SDS and BARNASE fusion gene, which resulted in complete sterility in both male and female reproductive organs in Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum), but did not affect plant growth or development, including the formation of all flower organs. Therefore, our research provides a general and effective tool to prevent transgene flow in GM plants. PMID- 26870058 TI - Evolution and Functional Insights of Different Ancestral Orthologous Clades of Chitin Synthase Genes in the Fungal Tree of Life. AB - Chitin synthases (CHSs) are key enzymes in the biosynthesis of chitin, an important structural component of fungal cell walls that can trigger innate immune responses in host plants and animals. Members of CHS gene family perform various functions in fungal cellular processes. Previous studies focused primarily on classifying diverse CHSs into different classes, regardless of their functional diversification, or on characterizing their functions in individual fungal species. A complete and systematic comparative analysis of CHS genes based on their orthologous relationships will be valuable for elucidating the evolution and functions of different CHS genes in fungi. Here, we identified and compared members of the CHS gene family across the fungal tree of life, including 18 divergent fungal lineages. Phylogenetic analysis revealed that the fungal CHS gene family is comprised of at least 10 ancestral orthologous clades, which have undergone multiple independent duplications and losses in different fungal lineages during evolution. Interestingly, one of these CHS clades (class III) was expanded in plant or animal pathogenic fungi belonging to different fungal lineages. Two clades (classes VIb and VIc) identified for the first time in this study occurred mainly in plant pathogenic fungi from Sordariomycetes and Dothideomycetes. Moreover, members of classes III and VIb were specifically up regulated during plant infection, suggesting important roles in pathogenesis. In addition, CHS-associated networks conserved among plant pathogenic fungi are involved in various biological processes, including sexual reproduction and plant infection. We also identified specificity-determining sites, many of which are located at or adjacent to important structural and functional sites that are potentially responsible for functional divergence of different CHS classes. Overall, our results provide new insights into the evolution and function of members of CHS gene family in the fungal kingdom. Specificity-determining sites identified here may be attractive targets for further structural and experimental studies. PMID- 26870059 TI - Maintaining Epigenetic Inheritance During DNA Replication in Plants. AB - Biotic and abiotic stresses alter the pattern of gene expression in plants. Depending on the frequency and duration of stress events, the effects on the transcriptional state of genes are "remembered" temporally or transmitted to daughter cells and, in some instances, even to offspring (transgenerational epigenetic inheritance). This "memory" effect, which can be found even in the absence of the original stress, has an epigenetic basis, through molecular mechanisms that take place at the chromatin and DNA level but do not imply changes in the DNA sequence. Many epigenetic mechanisms have been described and involve covalent modifications on the DNA and histones, such as DNA methylation, histone acetylation and methylation, and RNAi dependent silencing mechanisms. Some of these chromatin modifications need to be stable through cell division in order to be truly epigenetic. During DNA replication, histones are recycled during the formation of the new nucleosomes and this process is tightly regulated. Perturbations to the DNA replication process and/or the recycling of histones lead to epigenetic changes. In this mini-review, we discuss recent evidence aimed at linking DNA replication process to epigenetic inheritance in plants. PMID- 26870060 TI - Cell Wall Pectin and its Methyl-esterification in Transition Zone Determine Al Resistance in Cultivars of Pea (Pisum sativum). AB - The initial response of plants to aluminum (Al) is the inhibition of root elongation, while the transition zone is the most Al sensitive zone in the root apex, which may sense the presence of Al and regulate the responses of root to Al toxicity. In the present study, the effect of Al treatment (30 MUM, 24 h) on root growth, Al accumulation, and properties of cell wall of two pea (Pisum sativum L.) cultivars, cv Onward (Al-resistant) and cv Sima (Al-sensitive), were studied to disclose whether the response of root transition zone to Al toxicity determines Al resistance in pea cultivars. The lower relative root elongation (RRE) and higher Al content were founded in cv Sima compared with cv Onward, which were related to Al-induced the increase of pectin in root segments of both cultivars. The increase of pectin is more prominent in Al-sensitive cultivar than in Al-resistant cultivar. Aluminum toxicity also induced the increase of pectin methylesterases (PME), which is 2.2 times in root transition zone in Al-sensitive cv Sima to that of Al resistant cv Onward, thus led to higher demethylesterified pectin content in root transition zone of Al-sensitive cv Sima. The higher demethylesterified pectin content in root transition zone resulted in more Al accumulation in the cell wall and cytosol in Al-sensitive cv Sima. Our results provide evidence that the increase of pectin content and PME activity under Al toxicity cooperates to determine Al sensitivity in root transition zone that confers Al resistance in cultivars of pea (Pisum sativum). PMID- 26870061 TI - Gene Inactivation by CRISPR-Cas9 in Nicotiana tabacum BY-2 Suspension Cells. AB - Plant suspension cells are interesting hosts for the heterologous production of pharmacological proteins such as antibodies. They have the advantage to facilitate the containment and the application of good manufacturing practices. Furthermore, antibodies can be secreted to the extracellular medium, which makes the purification steps much simpler. However, improvements are still to be made regarding the quality and the production yield. For instance, the inactivation of proteases and the humanization of glycosylation are both important targets which require either gene silencing or gene inactivation. To this purpose, CRISPR-Cas9 is a very promising technique which has been used recently in a series of plant species, but not yet in plant suspension cells. Here, we sought to use the CRISPR Cas9 system for gene inactivation in Nicotiana tabacum BY-2 suspension cells. We transformed a transgenic line expressing a red fluorescent protein (mCherry) with a binary vector containing genes coding for Cas9 and three guide RNAs targeting mCherry restriction sites, as well as a bialaphos-resistant (bar) gene for selection. To demonstrate gene inactivation in the transgenic lines, the mCherry gene was PCR-amplified and analyzed by electrophoresis. Seven out of 20 transformants displayed a shortened fragment, indicating that a deletion occurred between two target sites. We also analyzed the transformants by restriction fragment length polymorphism and observed that the three targeted restriction sites were hit. DNA sequencing of the PCR fragments confirmed either deletion between two target sites or single nucleotide deletion. We therefore conclude that CRISPR-Cas9 can be used in N. tabacum BY2 cells. PMID- 26870062 TI - Editorial: Branching and Rooting Out with a CT Scanner: The Why, the How, and the Outcomes, Present and Possibly Future. PMID- 26870063 TI - Identification of a 467 bp Promoter of Maize Phosphatidylinositol Synthase Gene (ZmPIS) Which Confers High-Level Gene Expression and Salinity or Osmotic Stress Inducibility in Transgenic Tobacco. AB - Salinity and drought often affect plant growth and crop yields. Cloning and identification of salinity and drought stress inducible promoters is of great significance for their use in the genetic improvement of crop resistance. Previous studies showed that phosphatidylinositol synthase is involved in plant salinity and drought stress responses but its promoter has not been characterized by far. In the study, the promoter (pZmPIS, 1834 bp upstream region of the translation initiation site) was isolated from maize genome. To functionally validate the promoter, eight 5' deletion fragments of pZmPIS in different lengths were fused to GUS to produce pZmPIS::GUS constructs and transformed into tobacco, namely PZ1-PZ8. The transcription activity and expression pattern obviously changed when the promoter was truncated. Previous studies have demonstrated that NaCl and PEG treatments are usually used to simulate salinity and drought treatments. The results showed that PZ1-PZ7 can respond well upon NaCl and PEG treatments, while PZ8 not. PZ7 (467 bp) displayed the highest transcription activity in all tissues of transgenic tobacco amongst 5' deleted promoter fragments, which corresponds to about 20 and 50% of CaMV35S under normal and NaCl or PEG treatment, respectively. This implied that PZ7 is the core region of pZmPIS which confers high-level gene expression and NaCl or PEG inducible nature. The 113 bp segment between PZ7 and PZ8 (-467 to -355 bp) was considered as the key sequence for ZmPIS responding to NaCl or PEG treatment. GUS transient assay in tobacco leaves showed that this segment was sufficient for the NaCl or PEG stress response. Bioinformatic analysis revealed that the 113 bp sequence may contain new elements that are crucial for ZmPIS response to NaCl or PEG stress. These results promote our understanding on transcriptional regulation mechanism of ZmPIS and the characterized PZ7 promoter fragment would be an ideal candidate for the overexpression of drought and salinity responsive gene to improve crop resistance. PMID- 26870064 TI - Hydrogen Peroxide Alleviates Nickel-Inhibited Photosynthetic Responses through Increase in Use-Efficiency of Nitrogen and Sulfur, and Glutathione Production in Mustard. AB - The response of two mustard (Brassica juncea L.) cultivars differing in photosynthetic capacity to different concentrations of hydrogen peroxide (H2O2) or nickel (Ni) was evaluated. Further, the effect of H2O2 on photosynthetic responses of the mustard cultivars grown with or without Ni stress was studied. Application of 50 MUM H2O2 increased photosynthesis and growth more prominently in high photosynthetic capacity cultivar (Varuna) than low photosynthetic capacity cultivar (RH30) grown without Ni stress. The H2O2 application also resulted in alleviation of photosynthetic inhibition induced by 200 mg Ni kg(-1) soil through increased photosynthetic nitrogen-use efficiency (NUE), sulfur-use efficiency (SUE), and glutathione (GSH) reduced production together with decreased lipid peroxidation and electrolyte leakage in both the cultivars. However, the effect of H2O2 was more pronounced in Varuna than RH30. The greater increase in photosynthetic-NUE and SUE and GSH production with H2O2 in Varuna resulted from higher increase in activity of nitrogen (N) and sulfur (S) assimilation enzymes, nitrate reductase and ATP-sulfurylase, respectively resulting in enhanced N and S assimilation. The increased N and S content contributed to the higher activity of ribulose-1,5-bisphosphate carboxylase under Ni stress. Application of H2O2 also regulated PS II activity and stomatal movement under Ni stress for maintaining higher photosynthetic potential in Varuna. Thus, H2O2 may be considered as a potential signaling molecule for augmenting photosynthetic potential of mustard plants under optimal and Ni stress conditions. It alleviates Ni stress through the regulation of stomatal and non stomotal limitations, and photosynthetic-NUE and -SUE and GSH production. PMID- 26870065 TI - Savanna Tree Seedlings are Physiologically Tolerant to Nighttime Freeze Events. AB - Freeze events can be important disturbances in savanna ecosystems, yet the interactive effect of freezing with other environmental drivers on plant functioning is unknown. Here, we investigated physiological responses of South African tree seedlings to interactions of water availability and freezing temperatures. We grew widely distributed South African tree species (Colophospermum mopane, Combretum apiculatum, Acacia nigrescens, and Cassia abbreviata) under well-watered and water-limited conditions and exposed individuals to nighttime freeze events. Of the four species studied here, C. mopane was the most tolerant of lower water availability. However, all species were similarly tolerant to nighttime freezing and recovered within one week following the last freezing event. We also show that water limitation somewhat increased freezing tolerance in one of the species (C. mopane). Therefore, water limitation, but not freezing temperatures, may restrict the distribution of these species, although the interactions of these stressors may have species-specific impacts on plant physiology. Ultimately, we show that unique physiologies can exist among dominant species within communities and that combined stresses may play a currently unidentified role in driving the function of certain species within southern Africa. PMID- 26870066 TI - A Review of Auxin Response Factors (ARFs) in Plants. AB - Auxin is a key regulator of virtually every aspect of plant growth and development from embryogenesis to senescence. Previous studies have indicated that auxin regulates these processes by controlling gene expression via a family of functionally distinct DNA-binding auxin response factors (ARFs). ARFs are likely components that confer specificity to auxin response through selection of target genes as transcription factors. They bind to auxin response DNA elements (AuxRE) in the promoters of auxin-regulated genes and either activate or repress transcription of these genes depending on a specific domain in the middle of the protein. Genetic studies have implicated various ARFs in distinct developmental processes through loss-of-function mutant analysis. Recent advances have provided information on the regulation of ARF gene expression, the role of ARFs in growth and developmental processes, protein-protein interactions of ARFs and target genes regulated by ARFs in plants. In particular, protein interaction and structural studies of ARF proteins have yielded novel insights into the molecular basis of auxin-regulated transcription. These results provide the foundation for predicting the contributions of ARF genes to the biology of other plants. PMID- 26870067 TI - Genetic Adaptation vs. Ecophysiological Plasticity of Photosynthetic-Related Traits in Young Picea glauca Trees along a Regional Climatic Gradient. AB - Assisted population migration (APM) is the intentional movement of populations within a species range to sites where future environmental conditions are projected to be more conducive to growth. APM has been proposed as a proactive adaptation strategy to maintain forest productivity and to reduce the vulnerability of forest ecosystems to projected climate change. The validity of such a strategy will depend on the adaptation capacity of populations, which can partially be evaluated by the ecophysiological response of different genetic sources along a climatic gradient. This adaptation capacity results from the compromise between (i) the degree of genetic adaptation of seed sources to their environment of origin and (ii) the phenotypic plasticity of functional trait which can make it possible for transferred seed sources to positively respond to new growing conditions. We examined phenotypic variation in morphophysiological traits of six seed sources of white spruce (Picea glauca [Moench] Voss) along a regional climatic gradient in Quebec, Canada. Seedlings from the seed sources were planted at three forest sites representing a mean annual temperature (MAT) gradient of 2.2 degrees C. During the second growing season, we measured height growth (H2014) and traits related to resources use efficiency and photosynthetic rate (A max). All functional traits showed an adaptive response to the climatic gradient. Traits such as H2014, A max, stomatal conductance (g s ), the ratio of mesophyll to stomatal conductance, water use efficiency, and photosynthetic nitrogen-use efficiency showed significant variation in both physiological plasticity due to the planting site and seed source variation related to local genetic adaptation. However, the amplitude of seed source variation was much less than that related to plantation sites in the area investigated. The six seed sources showed a similar level of physiological plasticity. H2014, A max and g s , but not carboxylation capacity (V cmax), were correlated and decreased with a reduction of the average temperature of the growing season at seed origin. The clinal variation in H2014 and A max appeared to be driven by CO2 conductance. The presence of locally adapted functional traits suggests that the use of APM may have advantages for optimizing seed source productivity in future local climates. PMID- 26870068 TI - RNA-SEQ Reveals Transcriptional Level Changes of Poplar Roots in Different Forms of Nitrogen Treatments. AB - Poplar has emerged as a model plant for better understanding cellular and molecular changes accompanying tree growth, development, and response to environment. Long-term application of different forms of nitrogen (such as [Formula: see text]-N and [Formula: see text]-N) may cause morphological changes of poplar roots; however, the molecular level changes are still not well-known. In this study, we analyzed the expression profiling of poplar roots treated by three forms of nitrogen: S1 ([Formula: see text]), S2 (NH4NO3), and S3 ([Formula: see text]) by using RNA-SEQ technique. We found 463 genes significantly differentially expressed in roots by different N treatments, of which a total of 112 genes were found to differentially express between S1 and S2, 171 genes between S2 and S3, and 319 genes between S1 and S3. A cluster analysis shows significant difference in many transcription factor families and functional genes family under different N forms. Through an analysis of Mapman metabolic pathway, we found that the significantly differentially expressed genes are associated with fermentation, glycolysis, and tricarboxylic acid cycle (TCA), secondary metabolism, hormone metabolism, and transport processing. Interestingly, we did not find significantly differentially expressed genes in N metabolism pathway, mitochondrial electron transport/ATP synthesis and mineral nutrition. We also found abundant candidate genes (20 transcription factors and 30 functional genes) regulating morphology changes of poplar roots under the three N forms. The results obtained are beneficial to a better understanding of the potential molecular and cellular mechanisms regulating root morphology changes under different N treatments. PMID- 26870069 TI - Response: A commentary on "Eucalyptus obliqua seedling growth in organic vs. mineral soil horizons". PMID- 26870071 TI - Effects of Diffuse Light on Radiation Use Efficiency of Two Anthurium Cultivars Depend on the Response of Stomatal Conductance to Dynamic Light Intensity. AB - The stimulating effect of diffuse light on radiation use efficiency (RUE) of crops is often explained by the more homogeneous spatial light distribution, while rarely considering differences in temporal light distribution at leaf level. This study investigated whether diffuse light effects on crop RUE can be explained by dynamic responses of leaf photosynthesis to temporal changes of photosynthetic photon flux density (PPFD). Two Anthurium andreanum cultivars ('Pink Champion' and 'Royal Champion') were grown in two glasshouses covered by clear (control) and diffuse glass, with similar light transmission. On clear days, diffusing the light resulted in less temporal fluctuations of PPFD. Stomatal conductance (g s) varied strongly in response to transient PPFD in 'Royal Champion,' whereas it remained relatively constant in 'Pink Champion.' Instantaneous net leaf photosynthesis (P n) in both cultivars approached steady state P n in diffuse light treatment. In control treatment this only occurred in 'Pink Champion.' These cultivar differences were reflected by a higher RUE (8%) in 'Royal Champion' in diffuse light treatment compared with control, whereas no effect on RUE was observed in 'Pink Champion.' We conclude that the stimulating effect of diffuse light on RUE depends on the stomatal response to temporal PPFD fluctuations, which response is cultivar dependent. PMID- 26870070 TI - BdCESA7, BdCESA8, and BdPMT Utility Promoter Constructs for Targeted Expression to Secondary Cell-Wall-Forming Cells of Grasses. AB - Utility vectors with promoters that confer desired spatial and temporal expression patterns are useful tools for studying gene and cellular function and for industrial applications. To target the expression of DNA sequences of interest to cells forming plant secondary cell walls, which generate most of the vegetative biomass, upstream regulatory sequences of the Brachypodium distachyon lignin biosynthetic gene BdPMT and the cellulose synthase genes BdCESA7 and BdCESA8 were isolated and cloned into binary vectors designed for Agrobacterium mediated transformation of monocots. Expression patterns were assessed using the beta-glucuronidase gene GUSPlus and X-glucuronide staining. All three promoters showed strong expression levels in stem tissue at the base of internodes where cell wall deposition is most active, in both vascular bundle xylem vessels and tracheids, and in interfascicular tissues, with expression less pronounced in developmentally older tissues. In leaves, BdCESA7 and BdCESA8 promoter-driven expression was strongest in leaf veins, leaf margins, and trichomes; relatively weaker and patchy expression was observed in the epidermis. BdPMT promoter-driven expression was similar to the BdCESA promoters expression patterns, including strong expression in trichomes. The intensity and extent of GUS staining varied considerably between transgenic lines, suggesting that positional effects influenced promoter activity. Introducing the BdPMT and BdCESA8 Open Reading Frames into BdPMT and BdCESA8 utility promoter binary vectors, respectively, and transforming those constructs into Brachypodium pmt and cesa8 loss-of-function mutants resulted in rescue of the corresponding mutant phenotypes. This work therefore validates the functionality of these utility promoter binary vectors for use in Brachypodium and likely other grass species. The identification, in Bdcesa8-1 T-DNA mutant stems, of an 80% reduction in crystalline cellulose levels confirms that the BdCESA8 gene is a secondary-cell-wall-forming cellulose synthase. PMID- 26870072 TI - Chloroplast DNA Copy Number Changes during Plant Development in Organelle DNA Polymerase Mutants. AB - Chloroplast genome copy number is very high in leaf tissue, with upwards of 10,000 or more copies of the chloroplast DNA (ctDNA) per leaf cell. This is often promoted as a major advantage for engineering the plastid genome, as it provides high gene copy number and thus is expected to result in high expression of foreign proteins from integrated genes. However, it is also known that ctDNA copy number and ctDNA integrity decrease as cells age. Quantitative PCR (qPCR) allows measurement of organelle DNA levels relative to a nuclear gene target. We have used this approach to determine changes in copy number of ctDNA relative to the nuclear genome at different ages of Arabidopsis plant growth and in organellar DNA polymerase mutants. The mutant plant lines have T-DNA insertions in genes encoding the two organelle localized DNA polymerases (PolIA and PolIB). Each of these mutant lines exhibits some delay in plant growth and development as compared to wild-type plants, with the PolIB plants having a more pronounced delay. Both mutant lines develop to maturity and produce viable seeds. Mutants for both proteins were observed to have a reduction in ctDNA and mtDNA copy number relative to wild type plants at all time points as measured by qPCR. Both DNA polymerase mutants had a fairly similar decrease in ctDNA copy number, while the PolIB mutant had a greater effect of reduction in mtDNA levels. However, despite similar decreases in genome copy number, RT-PCR analysis of PolIA mutants show that PolIB expression remains unchanged, suggesting that PolIA may not be essential to plant survival. Furthermore, genotypic analysis of plants from heterozygous parents display a strong pressure to maintain two functioning copies of PolIB. These results indicate that the two DNA polymerases are both important in ctDNA replication, and they are not fully redundant to each other, suggesting each has a specific function in plant organelles. PMID- 26870073 TI - Regulation of WRKY46 Transcription Factor Function by Mitogen-Activated Protein Kinases in Arabidopsis thaliana. AB - Mitogen-activated protein kinase (MAPK) cascades are central signaling pathways activated in plants after sensing internal developmental and external stress cues. Knowledge about the downstream substrate proteins of MAPKs is still limited in plants. We screened Arabidopsis WRKY transcription factors as potential targets downstream of MAPKs, and concentrated on characterizing WRKY46 as a substrate of the MAPK, MPK3. Mass spectrometry revealed in vitro phosphorylation of WRKY46 at amino acid position S168 by MPK3. However, mutagenesis studies showed that a second phosphosite, S250, can also be phosphorylated. Elicitation with pathogen-associated molecular patterns (PAMPs), such as the bacterial flagellin-derived flg22 peptide led to in vivo destabilization of WRKY46 in Arabidopsis protoplasts. Mutation of either phosphorylation site reduced the PAMP induced degradation of WRKY46. Furthermore, the protein for the double phosphosite mutant is expressed at higher levels compared to wild-type proteins or single phosphosite mutants. In line with its nuclear localization and predicted function as a transcriptional activator, overexpression of WRKY46 in protoplasts raised basal plant defense as reflected by the increase in promoter activity of the PAMP-responsive gene, NHL10, in a MAPK-dependent manner. Thus, MAPK-mediated regulation of WRKY46 is a mechanism to control plant defense. PMID- 26870074 TI - OsSRO1a Interacts with RNA Binding Domain-Containing Protein (OsRBD1) and Functions in Abiotic Stress Tolerance in Yeast. AB - SRO1 is an important regulator of stress and hormonal response in plants and functions by interacting with transcription factors and several other proteins involved in abiotic stress response. In the present study, we report OsRBD1, an RNA binding domain 1- containing protein as a novel interacting partner of OsSRO1a from rice. The interaction of OsSRO1a with OsRBD1 was shown in yeast as well as in planta. Domain-domain interaction study revealed that C-terminal RST domain of OsSRO1a interacts with the N-terminal RRM1 domain of OsRBD1 protein. Both the proteins were found to co-localize in nucleus. Transcript profiling under different stress conditions revealed co-regulation of OsSRO1a and OsRBD1 expression under some abiotic stress conditions. Further, co-transformation of both OsSRO1a and OsRBD1 in yeast conferred enhanced tolerance toward salinity, osmotic, and methylglyoxal treatments. Our study suggests that the interaction of OsSRO1a with OsRBD1 confers enhanced stress tolerance in yeast and may play an important role under abiotic stress responses in plants. PMID- 26870077 TI - Editorial: Genomics and Effectomics of the Crop Killer Xanthomonas. PMID- 26870075 TI - Efficient Rutin and Quercetin Biosynthesis through Flavonoids-Related Gene Expression in Fagopyrum tataricum Gaertn. Hairy Root Cultures with UV-B Irradiation. AB - Transformed hairy roots had been efficiently induced from the seedlings of Fagopyrum tataricum Gaertn. due to the infection of Agrobacterium rhizogenes. Hairy roots were able to display active elongation with high root branching in 1/2 MS medium without growth regulators. The stable introduction of rolB and aux1 genes of A. rhizogenes WT strain 15834 into F. tataricum plants was confirmed by PCR analysis. Besides, the absence of virD gene confirmed hairy root was bacteria free. After six different media and different sources of concentration were tested, the culturing of TB7 hairy root line in 1/2 MS liquid medium supplemented with 30 g l(-1) sucrose for 20 days resulted in a maximal biomass accumulation (13.5 g l(-1) fresh weight, 1.78 g l(-1) dry weight) and rutin content (0.85 mg g(-1)). The suspension culture of hairy roots led to a 45-fold biomass increase and a 4.11-fold rutin content increase in comparison with the suspension culture of non-transformed roots. The transformation frequency was enhanced through preculturing for 2 days followed by infection for 20 min. The UV-B stress treatment of hairy roots resulted in a striking increase of rutin and quercetin production. Furthermore, the hairy root lines of TB3, TB7, and TB28 were chosen to study the specific effects of UV-B on flavonoid accumulation and flavonoid biosynthetic gene expression by qRT-PCR. This study has demonstrated that the UV B radiation was an effective elicitor that dramatically changed in the transcript abundance of ftpAL, FtCHI, FtCHS, FtF3H, and FtFLS-1 in F. tataricum hairy roots. PMID- 26870078 TI - Petunia, Your Next Supermodel? AB - Plant biology in general, and plant evo-devo in particular would strongly benefit from a broader range of available model systems. In recent years, technological advances have facilitated the analysis and comparison of individual gene functions in multiple species, representing now a fairly wide taxonomic range of the plant kingdom. Because genes are embedded in gene networks, studying evolution of gene function ultimately should be put in the context of studying the evolution of entire gene networks, since changes in the function of a single gene will normally go together with further changes in its network environment. For this reason, plant comparative biology/evo-devo will require the availability of a defined set of 'super' models occupying key taxonomic positions, in which performing gene functional analysis and testing genetic interactions ideally is as straightforward as, e.g., in Arabidopsis. Here we review why petunia has the potential to become one of these future supermodels, as a representative of the Asterid clade. We will first detail its intrinsic qualities as a model system. Next, we highlight how the revolution in sequencing technologies will now finally allows exploitation of the petunia system to its full potential, despite that petunia has already a long history as a model in plant molecular biology and genetics. We conclude with a series of arguments in favor of a more diversified multi-model approach in plant biology, and we point out where the petunia model system may further play a role, based on its biological features and molecular toolkit. PMID- 26870080 TI - Effects of NO2 and Ozone on Pollen Allergenicity. AB - This mini-review summarizes the available data of the air pollutants NO2 and ozone on allergenic pollen from different plant species, focusing on potentially allergenic components of the pollen, such as allergen content, protein release, IgE-binding, or protein modification. Various in vivo and in vitro studies on allergenic pollen are shown and discussed. PMID- 26870079 TI - Bioaugmentation with Endophytic Bacterium E6S Homologous to Achromobacter piechaudii Enhances Metal Rhizoaccumulation in Host Sedum plumbizincicola. AB - Application of hyperaccumulator-endophyte symbiotic systems is a potential approach to improve phytoremediation efficiency, since some beneficial endophytic bacteria are able to detoxify heavy metals, alter metal solubility in soil, and facilitate plant growth. The objective of this study was to isolate multi-metal resistant and plant beneficial endophytic bacteria and to evaluate their role in enhancing plant growth and metal accumulation/translocation. The metal resistant endophytic bacterial strain E6S was isolated from stems of the Zn/Cd hyperaccumulator plant Sedum plumbizincicola growing in metalliferous mine soils using Dworkin and Foster salts minimal agar medium with 1-aminocyclopropane-1 carboxylate (ACC) as the sole nitrogen source, and identified as homologous to Achromobacter piechaudii based on morphological and biochemical characteristics, partial 16S rDNA sequence and phylogenetic analysis. Strain E6S showed high level of resistance to various metals (Cd, Zn, and Pb). Besides utilizing ACC, strain E6S exhibited plant beneficial traits, such as solubilization of phosphate and production of indole-3-acetic acid. Inoculation with E6S significantly increased the bioavailability of Cd, Zn, and Pb in soil. In addition, bacterial cells bound considerable amounts of metal ions in the following order: Zn > Cd >Pb. Inoculation of E6S significantly stimulated plant biomass, uptake and bioaccumulation of Cd, Zn, and Pb. However, E6S greatly reduced the root to shoot translocation of Cd and Zn, indicating that bacterial inoculation assisted the host plant to uptake and store heavy metals in its root system. Inoculation with the endophytic bacterium E6S homologous to A. piechaudii can improve phytostabilization of metalliferous soils due to its effective ability to enhance in situ metal rhizoaccumulation in plants. PMID- 26870076 TI - Different Modes of Hydrogen Peroxide Action During Seed Germination. AB - Hydrogen peroxide was initially recognized as a toxic molecule that causes damage at different levels of cell organization and thus losses in cell viability. From the 1990s, the role of hydrogen peroxide as a signaling molecule in plants has also been discussed. The beneficial role of H2O2 as a central hub integrating signaling network in response to biotic and abiotic stress and during developmental processes is now well established. Seed germination is the most pivotal phase of the plant life cycle, affecting plant growth and productivity. The function of hydrogen peroxide in seed germination and seed aging has been illustrated in numerous studies; however, the exact role of this molecule remains unknown. This review evaluates evidence that shows that H2O2 functions as a signaling molecule in seed physiology in accordance with the known biology and biochemistry of H2O2. The importance of crosstalk between hydrogen peroxide and a number of signaling molecules, including plant phytohormones such as abscisic acid, gibberellins, and ethylene, and reactive molecules such as nitric oxide and hydrogen sulfide acting on cell communication and signaling during seed germination, is highlighted. The current study also focuses on the detrimental effects of H2O2 on seed biology, i.e., seed aging that leads to a loss of germination efficiency. The dual nature of hydrogen peroxide as a toxic molecule on one hand and as a signal molecule on the other is made possible through the precise spatial and temporal control of its production and degradation. Levels of hydrogen peroxide in germinating seeds and young seedlings can be modulated via pre-sowing seed priming/conditioning. This rather simple method is shown to be a valuable tool for improving seed quality and for enhancing seed stress tolerance during post-priming germination. In this review, we outline how seed priming/conditioning affects the integrative role of hydrogen peroxide in seed germination and aging. PMID- 26870081 TI - Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges. AB - The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured-making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development. PMID- 26870083 TI - What ails medical research in Pakistan? Role of institutions. PMID- 26870084 TI - Anorexia nervosa among teenage girls: Emerging or prevalent? AB - OBJECTIVES: To find out frequency of anorexia nervosa (AN) among teenage girls (TG) and to find out the knowledge and practice regarding anorexia nervosa among teenage girls. METHODS: A cross sectional study was conducted at higher secondary public school, Rawalpindi from June 2013 till December 2013. A sample of 100 female students of the age group 13-19 years were inducted by systematic sampling technique. Mixed pretested questionnaire was filled after informed verbal consent. Data was entered and analysed using SPSS version 20. RESULTS: Participants mean age was 15.81 +/- 1.323 years. Mean weight, mean height and mean body mass index were found to be 50.34 +/- 10.445 kg, 160.14 +/- 7.846 cm and 19.675 +/- 4.1477 kg/m(2) respectively. Anorexia nervosa was found in 42 (42%) teenage girls while 58 (58%) were not having anorexia nervosa. Sufficient knowledge and positive practice were found to be present in 57 (57%) and 49 (49%) respectively. Statistically no significant association was found between KP and AN (p=0.73). CONCLUSION: Anorexia nervosa is an emerging health concern in Pakistan. Anorexia prevalent behaviour was observed in almost half of the teenage girls. PMID- 26870082 TI - Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci. AB - Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID- 26870085 TI - The effect of Ramadan fasting on fetal development. AB - OBJECTIVE: To evaluate the effects of Ramadan fasting on fetal development and outcomes of pregnancy. METHODS: We performed this study in Antakya State Hospital of Obstetrics and Child Care, between 28 June 2014 and 27 July 2014 (during the month of Ramadan). A total of two hundred forty healthy pregnant women who were fasting during Ramadan, were included in the groups. The three groups were divided according to the trimesters. The each group was consisted of 40 healthy pregnant women with fasting and 40 healthy pregnant women without fasting. For evaluating the effects of Ramadan on fetus, ultrasonography was performed on all pregnant women in the beginning and the end of Ramadan. We used the essential parameters for the following measurements: increase of fetal biparietal diameter (BPD), increase of fetal femur length (FL), increase of estimated fetal body weight (EFBW), fetal biophysical profile (BPP), amniotic fluid index (AFI), and umbilical artery systole/diastole (S/D) ratio. RESULTS: No significant difference was found between the two groups for the fetal age, maternal weight gain (kilogram), estimated fetal weight gain (EFWG), fetal BPP, AFI, and umbilical artery S/D ratio. On the other hand, a statistically significant increase was observed in maternal weight in the second and third trimesters and a significant increase was observed in the amniotic fluid index in second trimester. CONCLUSION: In Ramadan there was no bad fetal outcome between pregnant women with fasting and pregnant women without fasting. Pregnant women who want to be with fast, should be examined by doctors, adequately get breakfast before starting to fast and after the fasting take essential calori and hydration. More comprehensive randomized studies are needed to explain the effects of fasting on the pregnancy and fetal outcomes. PMID- 26870086 TI - Predictor of cardiovascular risks in end stage renal failure patients on maintenance dialysis. AB - OBJECTIVE: Cardiovascular disease (CVD) is the main cause of morbidity and premature mortality in end stage renal failure patients (ESRD) receiving dialysis. The aim of our study was to evaluate the impact of various risk factors in this group of high CVD risk patients in local population. METHODS: We carried out a cross-sectional retrospective study in a single hospital. A total of 136 ESRF patients, consisted of 43 haemodialysis (HD) and 93 continuous ambulatory peritoneal dialysis (CAPD) patients, were recruited and followed up for 36 months duration. Midweek clinical and laboratory data were collected. The occurrence of existing and new CVD events was recorded. RESULTS: Multiple Logistic Regression showed pre-existing cardiovascular event (odds ratio, 4.124; 95% confidence interval [CI], 0.990 to 17.187), elevated total cholesterol level (odds ratio, 0.550; 95% CI, 0.315 to 0.963), elevated serum phosphate level (odds ratio, 5.862; 95% CI, 1.041 to 33.024) and elevated random blood glucose level (odds ratio, 1.193; 95% CI, 1.012 to 1.406) were significantly associated with occurrence of CVD events. CONCLUSIONS: History of cardiovascular event before the initiation of dialysis, elevated level of serum phosphate and random blood glucose levels are the risk factors of CVD whereas paradoxically a high total cholesterol level has CVD protective effect towards the ESRF patients. PMID- 26870087 TI - Longtime soaking of high concentration tranexamic acid in total hip arthroplasty: A prospective randomized controlled trial in 224 patients. AB - OBJECTIVES: To evaluate the efficacy and safety of intra-articular Soaking of high concentration Tranexamic Acid (TXA) in total hip arthroplasty. METHODS: From March 2013 to March 2014, 224 patients who underwent unilateral primary THA in our hospital was enrolled in this randomized, prospective double-blinded study. The patients were allocated into two groups according to intra-articular solution received: Intra-articular soaking of TXA group, Control group (physiologic saline). The solution was injected from intermuscular space following fixation of the implants and closure of articular capsule, short external rotators. Total blood loss, total volume of drainage and transfusion were recorded. Postoperative deep vein thrombosis and other complications was also measured. RESULTS: The mean total blood loss was 730+/-296 ml in intra-articular soaking of TXA group compared with 1048+/-295ml in control group (P<0.05). The postoperative mean total volume of drainage was 93+/-50 mL in intra-articular soaking of TXA group versus 312+/-136 mL in control group.22 patients (19.8%, control) and 6 patients (5.3%, Intra-articular soaking of TXA) required transfusion (P=0.001). Postoperative deep vein thrombosis and other complications were no statistical significance between the two groups. CONCLUSIONS: Intra-articular soaking of high concentration TXA with 2-hour clamping drain can reduce the total blood loss and transfusion rates in primary THA without significant increase in postoperative thrombotic complications. PMID- 26870088 TI - Dysmenorrhea among female medical students in King Abdulaziz University: Prevalence, Predictors and outcome. AB - OBJECTIVE: To determine the prevalence, predictors and outcome of dysmenorrhea among female medical students in King Abdulaziz University (KAU), Jeddah, Saudi Arabia. METHODS: A cross-sectional study was conducted among 435 medical students at KAU, Jeddah selected through stratified random sample method. A pre constructed, validated, self-administered questionnaire was used to collect personal and socio-demographic information. Data about menstrual history, stress, smoking were also collected. The severity of dysmenorrhea was scored by the "Visual Analogue Scale (VAS)". Descriptive and analytical statistics were conducted. RESULTS: The prevalence of dysmenorrhea was 60.9%. Logistic regression showed that heavy period was the first predictor of dysmenorrhea (aOR=1.94; 95% CI: 1.29- 2.91), followed by stress (aOR=1.90; 95% C.I.: 1.19-3.07). The prevalence of severe dysmenorrhea among the sufferers was 38.6%. Depressed mood was the commonest (80.8%) symptom accompanying dysmenorrhea. Regarding the outcome of dysmenorrhea, 67.5% of the sufferes reported emotional instability, while 28.3% reported absenteeism from the university. CONCLUSIONS: A high prevalence of dysmenorrhea was prevalent among medical students in King Abdulaziz University (KAU), Health promotion, screening programs, and stress management courses are recommended. PMID- 26870089 TI - New modification of modified bentall procedure (A single centre experience). AB - BACKGROUND AND OBJECTIVES: Modified Bentall procedure has become a gold standard in the treatment of combined aortic root and aortic valve diseases. Bleeding is an important predictor of morbidity and mortality after the Bentall operation. Our objective was to evaluate the early outcomes of Modified Button-Bentall procedure with cuff technique for aortic root replacement surgery regarding hemostasis. METHODS: A total number of 32 patients who underwent elective Bentall operation from January 2008 to December 2014 were included in the study. In 18 patients (Group I) modified Button-Bentall procedure with formation of cuff was used and in 14 patients (Group II) Modified Button technique without cuff formation was used for aortic root replacement. Data was analyzed using SPSS V16. Chi-square test, Fisher's Exact test and independent sample t-test was used to analyze Qualitative and Quantitative variables. RESULTS: Three patients in Group II and two patients in group I was in congestive cardiac failure pre-operatively. Out of thirty two patients two patients were having Aortic root dissection one in each group. Total bypass time and cross-clamp time were significantly high in Group I. There was no significant difference regarding duration of inotropic support, ventilation time, ICU stay and hospital stay time in patients of Group I and Group II. But post-op Chest drainage was very high in Group II 1158+451.25 ml versus 488.89+168.27 ml in group I (p-value <0.0001). There was one in hospital death in Group II. CONCLUSIONS: Formation of cuff of remnant of aorta during proximal anastomosis results in significant reduction in post-operative bleeding and was better in hospital outcomes. PMID- 26870090 TI - Comparison of emergency surgeries for obstructed colonic cancer with elective surgeries: A retrospective study. AB - OBJECTIVE: Colon cancer patients presented with obstruction were known to have worse postoperative morbidity and mortality rates, but conflicting data has been reported in recent years. We aimed to investigate postoperative complication rates, and short and long-term oncological outcomes in patients with colon cancer treated with either emergency surgery due to obstruction or elective surgery. METHODS: Two hundred fifty two patients were analyzed. Patients presented with obstruction and underwent an emergency surgery, and patients operated under elective circumstances were compared according to their demographic variables, tumor characteristics, and short and long term treatment outcomes. RESULTS: Distribution of age, gender and comorbidities were similar between both the groups. Need for an end colostomy was significantly higher in obstructed patients (22.7% vs 1.6%, respectively). Obstructed patients were tending to be at an advanced stage. Postoperative morbidity and mortality, and prognosis of colon cancer patients presented with obstruction is worse than patients operated under elective circumstances. CONCLUSIONS: Colon cancer patients presented with obstruction constitutes more than one quarter of all patients. These patients have significantly higher morbidity and mortality rates. Obstructed colon cancer usually appears at advanced stage. Primary resection and anastomosis is safe in most of the cases. PMID- 26870091 TI - Association of vitamin D receptor gene BsmI (A>G) and FokI (C>T) polymorphism in gestational diabetes among Saudi Women. AB - OBJECTIVE: Vitamin D receptor (VDR) gene polymorphism have a role in diabetes mellitus pathogenesis. Present study was conducted to determine VDR gene variants among Saudi gestational diabetics (GDM) in Madina, KSA. METHODS: This cross sectional study was conducted on 112 GDM patients and 218 normal healthy control. Age, body mass index and blood pressure levels were recorded. Serum triglycerides (mg/dl), total cholesterol, HDL-cholesterol, LDL-cholesterol, fasting blood glucose FBG and post-prandial blood glucose PPBG were estimated. Extracted DNA template was amplified by PCR reaction and genotyped for single nucleotide polymorphism of BsmI and FokI by restriction fragment length polymorphism-PCR (RFLP-PCR) analysis. RESULTS: FBG and PPBG levels in GDM patients were significantly elevated by +48.6% and +50%, respectively (P=0.005). Serum triglycerides, total cholesterol and LDL-cholesterol (mg/dl) levels in GDM patients were elevated significantly by +40.5% (P=0.005), +16% (P=0.01) and +30.8% (P=0.005), respectively. Serum HDL-cholesterol (mg/dl) showed significant decline by -10.5%. FokI VDR genotypes showed association with PPBG (P=0.05) among GDM patients. The Ff, FF and ff genotype percentage among GDM patients was 48.2%, 30.4% and 21.4%, respectively. FokI (F and f) and BsmI (B and b) alleles frequency showed no significant difference between GDM patients and control. Percentage BsmI and FokI total homozygous and heterozygous variants among GDM was 45.5% and 81.4%, respectively. CONCLUSION: VDR BsmI and FokI polymorphic marker not associated with Saudi GDM. PMID- 26870092 TI - Beneficial effects of silver foam dressing on healing of wounds with ulcers and infection control of burn patients. AB - OBJECTIVE: To assess the beneficial effects of silver foam dressing on the healing of wounds with ulcers and infection control of burn patients. METHODS: Eighty-four second-degree burn patients were selected and divided into a study group and a control group (n=42). After disinfection and cleaning, wound beds of the study group were covered with silver-containing soft-silicone foam dressing, and wound surfaces of the control group were wiped with 1% silver sulfadiazine cream (60 g/100 cm(2)). The two groups were checked weekly to observe wound healing progress and adverse reactions of the skin around wounds. Wound secretions were collected and subjected to bacterial culture. Related indices were recorded and quantified. RESULTS: Thirty seven cases of the study group (88.1%) and 36 cases of the control group (85.7%) recovered to normal, and 3 (7.1%) and 2 cases (4.8%) in the two groups failed to recover. The recovery rates of the two groups were similar (P>0.05), but unrecovered patients in the study group had significantly higher proportions of repaired wounds (P<0.05). Wounds of the study group were healed significantly more rapidly than those of the control group (22.3+/-3.1 vs. 25.1+/-4.4, P<0.05). The study group had significantly higher proportions of repaired wounds from Day 7 to Day 21 (P<0.05), but the difference became less obvious with extended time to Day 28. The bacterial culture-positive (exceeding 10(5) organisms per gram of tissue) rates of both groups significantly reduced after treatment (Day 7 for the study group and Day 14 for the control group), and the rate of the study group was significantly lower at last (P<0.05). The study and control groups were observed 134 and 149 person-times respectively, with the normal wound-surrounding skin rates of 96.3% (129/134) and 88.6% (132/149) (P>0.05 except for on Day 14). Except for on Day 28, the study group had significantly lower pain scores than those of the control group (P<0.05), especially on Day 7 and Day 14 (P<0.01). From Day 7 to Day 28, the study group was significantly less prone to burning sensation than the control group (P<0.05), but both groups felt anxious during dressing change (P>0.05). Dressing of the study group was changed significantly more easily (P<0.05), but the fixing outcomes were similar (P>0.05). CONCLUSION: Silver foam dressing rapidly, easily and safely resisted wound bacteria, promoted wound healing and shortened recovery time, effectively relieving the pain of patients. PMID- 26870093 TI - Screening for New Delhi metallo-beta-lactamase-1 in Enterobacteriaceae: Is there a role for the modified Hodge test? AB - OBJECTIVE: The New Delhi metallo-beta-lactamase-1 (NDM-1) enzyme is a plasmid encoded enzyme that inactivates carbapenem antibiotics. This study aims to ascertain if the modified Hodge test (MHT) has a role in screening for NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility. METHODS: Over a period of one year, all Enterobacteriaceae isolates from all clinical specimens with reduced susceptibility to at least one carbapenem were subjected to MHT and conventional polymerase chain reaction (PCR) detection of the NDM-1 gene. RESULTS: A total of 13,098 Enterobacteriaceae isolates were screened and 63 (0.48%) had reduced susceptibility to at least one carbapenem. Out of the 63 isolates, 45 (71.4%) were MHT-positive. The NDM-1 gene was detected in 18 of the 63 isolates (28.6%). All 18 PCR-positive isolates were also MHT-positive. Thus, the sensitivity and specificity of the MHT in detecting NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility are 100% and 40%, respectively. CONCLUSION: The MHT is a useful test to screen for the presence of NDM-1 in Enterobacteriaceae with reduced carbapenem susceptibility. However, due to its rather low specificity, all MHT-positive isolates should be subjected to alternative tests (e.g. PCR) for confirmation, especially if other types of carbapenemases (e.g. KPC) are prevalent. PMID- 26870094 TI - Concomitant presence of culture-proven active pulmonary tuberculosis in patients with chronic obstructive pulmonary disease - A hospital based study. AB - OBJECTIVE: To find out the prevalence of concomitant active pulmonary Tuberculosis (TB) in patients of Chronic Obstructive Pulmonary Disease (COPD) using the gold standard liquid and solid culture media for the detection of acid fast bacillus. METHODS: Eighty clinically and radiologically diagnosed cases of COPD of any severity, >=40 years of age with no previous history of anti tuberculous therapy were selected from department of Pulmonology, Jinnah Hospital, Lahore. Detailed demographic profile, clinical symptomatology and history of smoking were recorded. Sputum samples of these patients were subjected to ZiehlNeelsen (ZN) stain and culture on Lowenstein-Jensen (L.J) medium and Mycobacterium Growth Indicator Tube (MGIT) for the detection and isolation of Mycobacteriumtuberculosis (MTB). RESULTS: Out of 80 COPD patients, 6 (7.5%) were culture positive for acid fast bacillus consistent with active tuberculous infection. The concomitance was more prevalent in elderly, male, smokers. MGIT was a more sensitive and a rapid technique to detect the presence of mycobacterium as compared to LJ culture media and ZN stain. CONCLUSION: The prevalence of active TB in COPD patients was 7.5%. Detection was improved when liquid culture media was employed for the detection of acid fast bacillus. Regular monitoring and screening of patients with COPD for PTB should be routinely carried out in susceptible cohort to avoid cross spreading of infection and appropriate management. PMID- 26870095 TI - An evaluation of the effects of perioperatively administered fluids on ischemia/reperfusion injury. AB - OBJECTIVE: To investigate the effects of normal saline (0.9% NaCl) and 6% Hydroxyethyl Starch 130/0.4(HES) solution on Ischemia/Reperfusion (I/R) injury in patients undergoing knee arthroscopy operations with spinal anesthesia using a tourniquet. METHODS: The study comprised 48 ASA I-II patients undergoing knee arthroscopy with spinal anesthesia using a tourniquet. The patients were randomised into two groups and after standard monitoring two venous lines were introduced to obtain blood samples and to give intravenous therapy. In the control group (Group A) (n=21) 0.9% NaCl, 10 ml/kg/hours and in the study group (Group B) (n=19) 6% Hydroxyethyl Starch 130/0.4, 10 ml/kg/hours infusion were administered. Spinal anesthesia was applied with 12.5 mg hyperbaric bupivacaine to all patients. The tourniquet was applied and the operation was started when the sensorial block level reached T10 dermatome. Blood xanthine oxidase (XO) and malondialdehyde (MDA) levels as an indicator of ischemia and reperfusion injury were measured in samples before fluid infusion (t1), before tourniquet application (t2), 1 minute before tourniquet release (t3), and at 5 (t4) and 15 (t5) minutes after tourniquet release. RESULTS: No difference was observed between the two groups in respect of demographic parameters, the highest block level, duration before tourniquet application and tourniquet duration (p>0.05). The MDA level after tourniquet application and 15 minutes after tourniquet release was lower in Group B (p<0.05). XO levels were not different (p>0.05). CONCLUSION: In this study 6% Hydroxyethyl Starch 130/0.4 solution reduced MDA level which is an indicator of lipid peroxidation. 6% Hydroxyethyl Starch 130/0.4 solution may be beneficial for Ischemia/reperfusion injuries. PMID- 26870096 TI - Achieving fertility control through woman's autonomy and access to maternal healthcare: Are we on track? In-depth analysis of PDHS-2012-13. AB - BACKGROUND AND OBJECTIVE: Fertility control preferences and maternal healthcare have recently become a major concern for developing nations with evidence suggesting that low fertility control rates and poor maternal healthcare are among major obstructions in ensuring health and social status for women. Our objective was toanalyze the factors that influence women's autonomy, access to maternal healthcare, and fertility control preferences in Pakistan. METHODS: Data consisted of 11,761 ever-married women of ages 15-49 years from PDHS, 2012-13. Variables included socio-demographics, women's autonomy, fertility control preferences and access to maternal healthcare. RESULTS: Findings from multivariate analysis showed that women's younger age, having less than three number of children and independent or joint decision-making (indicators of high autonomy) remained the most significant predictors for access to better quality maternal healthcare and better fertility control preferences when other variables were controlled. CONCLUSION: Women's access to good quality maternal health care and fertility control preferences are directly and indirectly influenced by their demographic characteristics and decision-making patterns in domestic affairs. PMID- 26870097 TI - Comparison of outcomes between endoscopic surgery and conventional nasal packing for epistaxis in the posterior fornix of the inferior nasal meatus. AB - OBJECTIVE: To investigate the clinical features of epistaxis in the posterior fornix of the inferior nasal meatus and compare the treatment outcomes of endoscopic surgery and conventional nasal packing for this intractable form of epistaxis. METHODS: Between August 2011 and August 2014, the medical records of 53 adult patients with idiopathic epistaxis in the posterior fornix of the inferior nasal meatus diagnosed by nasal endoscopy were obtained from our department. Of these, 38 patients underwent endoscopic surgery (surgery group) and 15 received a nasal pack (packing group). The patients' background characteristics, incidence of re-bleeding, extent of discomfort after treatment as assessed using a 10-point visual analogue scale (VAS) and incidence of nasal cavity adhesion after treatment were analysed. RESULTS: There were no significant differences in background characteristics between the two groups. The incidence of re-bleeding (0/38 vs. 4/15, surgery vs. control, P = 0.001), VAS score for discomfort (2.4 +/- 1.4 vs. 7.6 +/- 1.0, surgery vs. control, P = 0.001) and incidence of nasal cavity adhesion after treatment (2/38 vs. 7/15, surgery vs. control, P = 0.007) were significantly lower in the surgery group than in the packing group. CONCLUSION: Endoscopic surgery is superior to conventional nasal packing for the management of epistaxis in the posterior fornix of the inferior nasal meatus. During surgery, it is crucial to expose the bleeding sites by shifting the inferior turbinate inward by fracture. PMID- 26870098 TI - Feasibility of using Arabic Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression among patients attending Accident and Emergency at a University Hospital setting in Riyadh, Saudi Arabia. AB - OBJECTIVE: To evaluate the feasibility of using Arabic Hospital Anxiety and Depression Scale (HADS) to assess depression and anxiety among patients attending accident and emergency (A & E) at a University Hospital setting in Riyadh, Saudi Arabia. METHODS: In this prospective observational study translated questionnaire of HADS was used for patients aged 18 years or above who presented to A & E at King Khalid University Hospital in Riyadh, Saudi Arabia. The study included 257 patients as per an agreed inclusion criteria. The study quantified depression and anxiety and its association with demographic and or illness related variables using SPSS. RESULTS: Out of 257 participants, the dominant age group, ranged between 18-30 years (40.9%) with female participants (55.3%) outweigh the male among all. The overall occurrence of depression was 27.2% (95% Confidence Interval (CI): 21.8 % to 32.6%) and anxiety was 23% (17.8% to 28.2%CI). Marital, educational and economic status of participants, were statistically significantly associated (p<0.05) with the levels of anxiety whereas age, marital, education, economic and employment status were associated (p<0.05) with the levels of depression. CONCLUSION: In the A & E setting at University Hospital in Saudi Arabia, comorbid depression and anxiety is not uncommon as enumerated by using HADS. The identified cases could then be sent for appropriate psychiatric treatment promptly not only to improve quality of individual care but also to reduce the overall health care costs in local context. PMID- 26870099 TI - Comparison for efficacy of general exercises with and without mobilization therapy for the management of adhesive capsulitis of shoulder - An interventional study. AB - OBJECTIVE: The aim of this work was to evaluate the effectiveness of exercise with manual therapy and exercise alone in adhesive capsulitis of the shoulder. METHOD: This randomized study was conducted at institute of physical medicine and rehabilitation Dow University of Health Sciences, Karachi between January, 2014 and July, 2014. Forty four participant age between 25-40 years were recruited. Twenty two participants were allocated to exercise and manual therapy group and 22 participants were allocated to exercise only group. Exercise and manual therapy group received general exercises and Maitland mobilization on shoulder joint whereas exercise group only received general exercises. Both interventions were carried out 3 times a week for 5 consecutive weeks. Pre and post intervention scores of Visual analogue scale (VAS), range of movement and Shoulder Pain and Disability Index (SPDI) were recorded. Paired sample t-test was used to analyze the results within groups. RESULTS: After 5 weeks of intervention both groups made significant improvements in all outcome measures (p < 0.001). Intra group analysis showed no significant difference between two groups (p > 0.05). Mean VAS and SPADI difference was 2.23 and 22 in General exercise & manual therapy group and 2.33 and 23 in General exercise group respectively. CONCLUSION: Both exercises with manual therapy and exercises alone are equally effective in the management of adhesive capsulits of the shoulder joint. PMID- 26870100 TI - Alarming high prevalence of metabolic syndrome among Jordanian adults. AB - OBJECTIVE: To evaluate the prevalence and the individual components of metabolic syndrome (MetS) in Jordanian adults. METHODS: In this cross sectional study, 630 adult subjects (308 men and 322 women) aged between 20-70 years were recruited from the clinics at the King Hussein Medical Center. The diagnosis of MetS was made according to the International Diabetes Federation (IDF) criteria-2005. Blood samples were collected after 10-12 hours overnight fasting and serum was obtained for biochemical analysis. RESULTS: The prevalence of metabolic syndrome according to IDF criteria was 51% (46.4% in men and 55.3% in women). Prevalence of increased waist circumference in the total sample was 71.6%, 46% for high blood pressure, 42.4% for elevated fasting blood glucose, 43.5% for low high density lipoprotein, and 50.2% for hypertriglyceridemia. CONCLUSION: The prevalence and individual components of MetS in Jordan were high. Screening of MetS is needed at national level to reduce the incidence of Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). PMID- 26870101 TI - Resistance patterns of multidrug resistant Acinetobacter baumannii in an ICU of a tertiary care hospital, Malaysia. AB - BACKGROUNDS & OBJECTIVE: Antimicrobial resistance is a major health problem worldwide in hospitals. The main contributing factors are exposures to broad spectrum antimicrobials and cross-infections. Understanding the extent and type of antimicrobial use in tertiary care hospitals will aid in developing national antimicrobial stewardship priorities. METHODS: In this study, we have analyzed the antimicrobial agents' usage for acquisition of multidrug resistant using retrospective, cross-sectional, single-centre study in a multidisciplinary ICU at tertiary care hospital. RESULTS: Acinetobacter baumannii (ACB) was isolated in various specimens from 662 patients. From these, 136 patients who were diagnosed with Ventilator-associated pneumonia (VAP) caused by ACB were included into the study. In our study, MDR strain accounts for 51% of all VAP cases caused by ACB. The development of ACB VAP were 10.5 + 6.4 days for MDR strains compared to susceptible organism (7.8 + 4.5 days) and had significantly longer ICU stay. CONCLUSION: The study concludes that prudent use of antimicrobial agents is important to reduce acquisition of MDR ACB. PMID- 26870102 TI - Use of recombinant factor VIIa in uncontrolled gastrointestinal bleeding after hematopoietic stem cell transplantation among patients with thrombocytopenia. AB - BACKGROUND AND OBJECTIVE: Recombinant-activated factor VII (rVIIa) is a vitamin K dependent glycoprotein that is an analog of the naturally occurring protease. It has an off-label use to control life-threatening bleeding that is refractory to other measures and was shown to decrease transfusion requirements. Gastrointestinal (GI) bleeding is a severe complication following hematopoietic stem cell transplantation (HSCT) in patients with thrombocytopenia, while hemostatic measures based on antifibrinolytic or transfusion therapy may not always be successful. The present study investigated the treatment with rFVIIa in severe GI bleeding among thrombocytopenia patients undergoing HSCT. METHODS: rFVIIa was given as a single dose of 60MUg/kg in patients with GI bleeding following hematopoietic stem cell transplantation (HSCT). RESULTS: Among all patients enrolled, 12 (75%) of 16 patients obtained a response, of which 5 achieved a complete response and 7 achieved a partial response. The 4 remiaing patients (25%) had no response. Nine patients (56.3%) died in a follow-up of 90 days. No thromboembolic events wereassociated with the drug administration occurred. CONCLUSIONS: Our study showed that rFVIIa may represent an additional therapeutic option in such cases. PMID- 26870103 TI - Frequency and determinants of Hepatitis B and C virus in general population of Farash Town, Islamabad. AB - BACKGROUND AND OBJECTIVE: Both Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are rapidly spreading in the developing countries. Both of them are blood borne and are transmitted through un-screened blood transfusion, inadequately sterilized needles and equipment. According to WHO's criteria of endemicity, Pakistan has high disease burden of Hepatitis B and C. The present study was planned to determine the frequency and to identify the risk factors of hepatitis B and C virus in the general community of Farash town. METHODS: This descriptive study was carried out in Al Nafees Medical Hospital Lab, from January 2013 to December 2013. Both the genders and all age groups were included in the study. All the patients who fulfilled the inclusion criteria had given a written consent. Data was collected through questionnaire and was analyzed on Statistical Package for Social Sciences (SPSS) version 21. RESULTS: Three-hundred and forty five patients were studied. Among these 92 (27%) were males and 253(73%) were female, 33% of them had hepatitis C, 9% had hepatitis B. History of injections was reported in all of the patients. Visit to community barbers was present in 58.6% and 41% cases of hepatitis B and C. History of dental procedures was obtained in 7(24%) and 15(13%) patients of hepatitis B and C. CONCLUSION: Major contributors for Hepatitis B and C in Farash town are use of unsterilized therapeutic injections and visit to community barbers. Education of the barbers regarding sterilization may help in reducing the burden of infection in this community. PMID- 26870104 TI - Validity of moyers mixed dentition analysis for Saudi population. AB - OBJECTIVES: To evaluate the applicability of Moyers probability tables and to formulate more accurate mixed dentition prediction tables in the Saudi population. METHODS: A cross-sectional study was conducted at the College of Dentistry, Kind Saud University, Saudi Arabia. The data were collected from 410 (203 males and 207 females) orthodontic study models, which had erupted mandibular permanent incisors, maxillary, mandibular canines and premolars. The mesiodistal widths were measured using a digital caliper with an accuracy of 0.01 mm. Student's paired t-test was used to compare the mean width values derived from this study with the values derived using the Moyers table. Simple linear regression was used to evaluate the linear relationship between the combined mesiodistal widths of the mandibular permanent incisors and the canine-premolar segments in each dental arch. RESULTS: The regression equations for the maxillary canine-premolar segment (males: Y=10.27+0.48X; females: Y=11.71 + 0.39X) and the mandibular canine-premolar segment (males: Y=9.71 + 0.40X; females: 11.28 + 0.39X) were used to formulate new probability tables on the Moyers pattern. Statistically significant differences were observed between predicted widths in our subjects and the widths obtained using Moyers tables. CONCLUSIONS: The new prediction tables derived in this study provided a more precise mixed dentition space analysis than Moyers prediction tables in estimating tooth dimensions in the Saudi population. PMID- 26870105 TI - Reconstruction of post burn scalp alopecia by using expanded hair-bearing scalp flaps. AB - BACKGROUND AND OBJECTIVE: Tissue expansion is a time-tested and frequently used procedure for utilizing local tissue to replace large defects. We aimed to assess the success & complications of tissue expansion in correction of post burn scalp alopecia. METHODS: In this study, 30 patients of scalp burn alopecia of 5 to 35 years age group were treated with tissue expansion of the scalp at Bahawal Victoria Hospital from January 2013 to December 2014. The area of the scalp loss was within 1/5 to 2/5. Our technique employed an insertion site distal to the area needed to be expanded, attempting to minimize complication like extrusion & wound dehiscence. The patients were followed-up weekly during first month and then fortnightly for next four months. RESULT: Our study involved 8 male (26.67%) and 22 female subjects (73.33%) with a mean age of 21years. Flame burn accounted for the mostly 53.3% (n=16) of scalp burns & parieto-temporal region was most commonly affected in 33.4% (n=10) of subjects. Desired aesthetic results were achieved in all the patients without any major complication. Minor complication included mild infection in 8 (26.67%), seroma in 4 (13.33%) & wound dehiscence in 2 (6.67%) patients. CONCLUSION: Tissue expansion is a simple, safe, & efficient technique for aesthetic scalp reconstruction. With a simple modification of distal incision and tunneling, we succeeded in minimizing complications. Versatile design of the expanded scalp flap can distribute the expanded hair bearing scalp properly in the reconstructed recipient site. PMID- 26870106 TI - Polymorphisms in NF-kappaB pathway genes & their association with risk of lung cancer in the Chinese population. AB - OBJECTIVE: To investigate the association of NFKB1 -94 ins/del ATTG, NFKBIA 826C>T and NFKBIA -881A>G polymorphisms with risk of lung cancer in a Chinese population. METHODS: Genotyping of the polymorphisms were performed on 1,436 subjects (718 cases and 718 controls) by using PCR-RFLP technique, followed by DNA sequencing. RESULTS: We found a significant risk reduction associated with heterozygous ins/del (OR=0.705, 95% CI=0.566-0.878, P=0.002) and variant del/del (OR=0.342, 95% CI=0.221-0.528, P<0.001) genotypes of the NFKB1 polymorphism. In contrast, the heterozygous and variantgenotypes of theNFKBIA polymorphisms showed association with increased lung cancer risk (NFKBIA -826 CT,OR=1.256, 95%CI=1.004 1.572, P=0.046; TT,OR=1.773, 95% CI=1.131-2.778, P=0.013; NFKBIA -881 AG,OR=1.277, 95% CI=1.023-1.599, P=0.031; GG,OR=1.801, 95% CI=1.169-2.775, P=0.008). Several genotypic combinations of the three polymorphisms also showed significant association with lung cancer risk. The risk association of NFKB1 polymorphism remained significant when analyses were done according to gender and smoking status (P<0.05). The significance of NFKBIA risk association was not observed when gender-specific analyses were made (P>0.05), while only NFKBIA -881 GG genotype showed significant risk association among smokers when analyzed according to smoking status (P=0.032). CONCLUSIONS: Polymorphisms in NFKB1 and NFKBIAgenes were associated with risk of lung cancer. PMID- 26870107 TI - Association between thyroid hormone levels and insulin resistance and body mass index. AB - OBJECTIVE: Previous studies have shown an association between thyroid function and insulin resistance and obesity. We compared insulin resistance and body mass index (BMI) in patients with normal TSH levels (2.5-4.2 uIU/mL), patients diagnosed with subclinical hypothyroidism, and healthy control subjects. METHODS: The study included 104 subjects and was conducted at the Taksim Education and Research Hospital. The subjects were divided into three groups according to TSH levels: Group 1 (high-normal), TSH levels were 2.5-4.2 uIU/mL (n=33); Group 2 (subclinical hypothyroidism), TSH levels were 4.2-10 uIU/mL (n=42); and Group 3 (healthy control), TSH levels were 0.27-2.5 uIU/mL (n=29). The fT3 and fT4 levels were within normal limits in all groups. Insulin resistance and BMI were compared among groups. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin resistance. RESULTS: HOMA-IR and BMI were not significantly different among groups (p>0.05). A significant positive correlation was found between BMI and HOMA-IR in the high-normal TSH (p>0.059) and subclinical hypothyroidism (p>0.05) groups. CONCLUSIONS: HOMA-IR and BMI are important for the assessment of diabetes and cardiovascular diseases. We found no significant difference in HOMA-IR and BMI values among the three TSH reference range groups. PMID- 26870108 TI - Epidemiology of intestinal parasitic infections in school children in Ghazni Province, eastern Afghanistan. AB - OBJECTIVE: To estimate the prevalence of intestinal parasites and their species in Afghan school children and to establish appropriate treatment methods for detected pathogens. METHODS: Parasitological examination of stool samples collected from 1369 children aged 8-18, students of the Jahan Malika High School in Ghazni Province in eastern Afghanistan, was conducted in the period November 2013-April 2014. Three stool samples were collected from each patient every second day; the samples were fixed in 10% formalin and tested by light microscopy using the methods of direct smear in Lugol's solution, decantation in distilled water, and Fulleborn's flotation. RESULTS: Of 535 examined children (39.1% of the study group) were infected with nematodes (n=324), cestodes (n=118), trematodes (n=12), and protozoa (n=228), 132 were diagnosed with co-infections (mainly ascariasis+giardiasis, ascariasis+hymenolepiasis) and received single or combined therapy. CONCLUSIONS: The Afghan community is an example of population characterized by a high rate of parasitic infections. Owing to high prevalence of multiple infections among inhabitants of Afghanistan, it seems that a mass deworming campaign with a single-dose chemotherapy may prove ineffective in eradicating intestinal parasites in the local population. PMID- 26870109 TI - Breast cancer recurrence after sentinel lymph node biopsy. AB - OBJECTIVE: To look into the pattern of breast cancer recurrence following mastectomy, breast conservative surgery and radiotherapy or chemotherapy after SLNB at our institution. METHODS: Between January 2005 and December 2014, all patients diagnosed with breast cancer with clinically negative axilla, underwent SLNB. We reviewed their medical records to identify pattern of cancer recurrence. RESULTS: The median follow-up was 35.5 months. Eighty five patients (70.8%) had a negative sentinel lymph node (SLN) and subsequently had no further axillary treatment, one of them (1.2%) developed axillary recurrence 25 months postoperatively. Twenty five patients (20.8%) had a positive SLN (macrometastases) and subsequently had immediate axillary lymph node dissection (ALND). Ten patients (8.3%) had a positive SLN (micrometastases). In the positive SLN patients (macrometastases and micrometastases), there were two ipsilateral breast recurrences (5.7%), seen three and four years postoperatively. Also in this group, there was one (2.9%) distant metastasis to bone three years postoperatively. CONCLUSION: In this series, the clinical axillary false negative rate for SLNB was 1.2% which is in accordance with the published literature. This supports the use of SLNB as the sole axillary staging procedure in breast cancer patients with negative SLNB. Axillary lymph node dissection can be safely omitted in patients with micrometastases in their sentinel lymph node(s). PMID- 26870110 TI - Gender differences among discrimination & stigma experienced by depressive patients in Pakistan. AB - OBJECTIVE: This study aims to examine Gender Difference in the level of Discrimination and Stigma experienced by people diagnosed with Major Depressive Disorder in Pakistan. It was hypothesized that Women diagnosed with Depression are likely to be experiencing more Discrimination and Internalized Stigma in comparison to Men. METHODS: This is a Cross Sectional Study. Thirty eight patients diagnosed with Major Depressive Disorder recruited from different Government Sector Hospitals of Lahore; were approached after obtaining informed consent. Discrimination and Stigma were measured through Discrimination and Stigma Scale and Internalized Stigma of Mental Illness Inventory respectively. RESULTS: Both Men and Women experience considerably high level of associated Stigma and Discrimination due to their Mental Illness. However, Women in comparison to Men experience significantly greater level of Internalized Stigma especially in domains of Discrimination Experience and Social Withdrawal. CONCLUSION: The findings of this study highlight the fact that people with Depression can be more benefited with psychological treatment if dealing with Stigma and Discrimination is also addressed in Intervention Plans. PMID- 26870111 TI - The predictive factors for lymph node metastasis in early gastric cancer: A clinical study. AB - OBJECTIVE: To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. METHODS: We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. RESULTS: In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. CONCLUSION: The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients. PMID- 26870114 TI - Four-year follow-up of corneal aberrations and visual functions of myopic patients after laser in situ keratomileusis. AB - OBJECTIVE: To report on 4-year follow-up of corneal higher-order aberrations and daily visual functions of myopic patients after laser in situ keratomileusis (LASIK). METHODS: One hundred thirty four eyes of 67 patients who underwent LASIK guided by aspherical ablation were included in this study. The vision, corneal spherical aberration (SphA) and Coma were recorded before LASIK and at 6 month and 4 year after LASIK. The evaluation of the questionnaire about daily visual functions was performed by the same physician after LASIK. RESULTS: No eye decreased the BCVA during 4 year follow-up. The effect index and safety index were 1.08+/-0.16, 1.11+/-0.17 and 1.12+/-0.16, 1.13+/-0.14 respectively at 6 month and 4 year post-LASIK. After LASIK the corneal SphA and Coma were significantly increased, however the difference between 6 month and 4 year post LASIK was no statistical significance. Most patients (94.3%-92.4%) felt satisfaction or high satisfaction about the ability to perform each daily visual function after LASIK. Meanwhile there was still about 7.4%-9.2% patients who complained that they could not drive at night. Further analysis showed that the score of driving at night was negative correlation with corneal SphA (r=-0.645, p=0.040; r=-0.688, p=0.040 at 6 month and 4 year post-LASIK respectively). CONCLUSIONS: Our four-year follow-up outcomes indicated that the myopic patients after LASIK had the long-term stable corneal aberration and satisfaction of daily visual functions. PMID- 26870112 TI - Ventilator-associated pneumonia in critically ill patients with intensive antibiotic usage. AB - OBJECTIVE: Ventilator-associated pneumonia (VAP) is an infection with high mortality and morbidity that prolongs the length of stay in the intensive care unit (ICU) and hospitalisation. VAP is one of the most common infections in critically ill patients. This study aimed to prospectively determine the VAP rate and associated factors in critically ill patients with intensive antibiotic usage during a one-year period. METHODS: In total, 125 out of 360 patients admitted to the intensive care unit during the one-year study period (September 2010-2011) were included for follow-up for VAP diagnosis. Demographic data, APACHE II scores, diagnoses on admission, clinical pulmonary infection scores (CPIS), CRP, procalcitonin, risk factors for infection, time to VAP diagnosis, and bacteriological culture results were recorded. All data were assessed in terms of ICU, hospital and 28-day mortality. RESULTS: In total, 56 (45%) out of 125 patients were diagnosed with VAP. In addition, 91% of patients diagnosed with VAP were administered antibiotics before diagnosis. In the VAP patients, the mortality rates were 48, 68 and 71% for 28-day, ICU and hospital mortality, respectively. CONCLUSION: The coexistence of clinical and microbiological parameters should not be sought when diagnosing VAP in patients who use antibiotics intensively. VAP can be diagnosed when CPIS<=6 in cases with sufficient microbiological evidence. This strategy may decrease mortality by preventing a delay in therapy. PMID- 26870113 TI - Factors associated with utilization of antenatal care services in Balochistan province of Pakistan: An analysis of the Multiple Indicator Cluster Survey (MICS) 2010. AB - OBJECTIVE: The study was conducted to identify factors affecting the utilization of Antenatal Care (ANC) in Balochistan Province, Pakistan. METHODS: Data on ANC utilization, together with social and economic determinants, were derived from a Multiple Indicator Cluster Survey (MICS) conducted in Balochistan in 2010. The analysis was conducted including 2339 women who gave birth in last two years preceding the survey. The researchers established a model to identify influential factors contributing to the utilization of ANC by logistic regression; model selection was by Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC). RESULTS: Household wealth, education, health condition, age at first marriage, number of children and spouse violence justification were found to be significantly associated with ANC coverage. Literate mothers are 2.45 times more likely to have ANC, and women whose newborns showed symptoms of illness at birth that needed hospitalization are 0.47 times less likely to access ANC. Women with an increase in the number of surviving children are 1.07 times less likely to have ANC, and those who think their spouse violence is socially justified are 1.36 times less likely to have ANC. The results draw attention towards evidence based planning of factors associated with utilization of ANC in the Balochistan province. CONCLUSION: The study reveals that women from high wealth index and having education had more chances to get ANC. Factors like younger age of the women at first marriage, increased number of children, symptoms of any illness to neonates at birth that need hospitalization and women who justify spouse violence had less chances to get ANC. Among components of ANC urine sampling and having tetanus toxoid (TT) in the last pregnancy increased the frequency of visits. ANC from a doctor decreased the number of visits. There is dire need to reduce disparities for wealth index, education and urban/rural living. PMID- 26870115 TI - The association between coping method and distress in infertile woman: A cross sectional study from Turkey. AB - OBJECTIVES: To assess the distress level in infertile women and their coping skills. METHODS: One hundred and twenty-seven infertile women who had been referred to the Family Planning and Infertility Research and Practice Center (IRPC) of a university hospital to receive therapy between June 2012-2013 were enrolled in this study. Several surveys, including the "Infertile Woman Identification Form", the "Infertility Distress Scale (IDS)" and the "Ways of Coping Inventory (WCI)," were used as data collection tools. RESULTS: The mean age of the women who participated in the study was 32.34 +/- 5.44. They had been on therapy for 3.95 +/- 3.21 years and had been referred for therapy 2.73 +/- 1.76 times. The mean score of the IDS was determined to be 37.0 +/- 9.7 (23-66), and the mean score of the WCI subscale was 1.86 +/- 0.55 (0.5-3.0). In the IDS and WCI subscales, statistically significant negative relationships were detected between "Optimism" (r=-0.327), "Seeking Social Support" (r=-0.255), and "Self Confidence" (r=-0.305), whereas there were statistically significant positive relationships between "Helplessness" (r=0.376) and "Submissiveness" (r=0.278) (p<0.01). CONCLUSION: The women who developed negative coping strategies had higher infertility distress scores than other women. PMID- 26870116 TI - Clinical characteristics of patients with diabetic ketoacidosis at the Intensive Care Unit of a University Hospital. AB - OBJECTIVES: The aims of this study were assessing the frequency of clinical characteristics of patients with severe Diabetic ketoacidosis (DKA) who were admitted to the intensive care unit (ICU) and investigating the relationship between paraclinical (glucose, anion gap, and serum bicarbonate) and clinical parameters in patients with severe DKA. METHOD: A retrospective chart review of all adult patients with DKA who were admitted to the ICU at King Abdulaziz University Hospital, Jeddah, Saudi Arabia between January 2012 and December 2013. The data collected include the demographic data, clinical presentation, precipitating factors, duration of hospital stay and mortality rate. The data were analyzed using STAT software. RESULTS: A total of 60 patients were included. Of these, 50 were men (83.3%). The median age was 23 years (ranging 18-29 years). Newly diagnosed diabetics accounted for 15 (25%) of the cases; the remainder were previously known patients of type1 diabetes on treatment. The main precipitating factors of DKA were insulin treatment cessation (87.5%) and infection/sepsis (39.6%). Serum blood glucose, serum bicarbonate level, and the calculated anion gap did not significantly correlate with clinical parameters of severe DKA. CONCLUSION: Most patients with severe DKA who were admitted to the ICU of our institution presented with gastrointestinal symptoms. Non-compliance to insulin therapy was the main precipitating factor of DKA. PMID- 26870117 TI - Fatty acid composition of diets of early school-age children and its health implications. AB - OBJECTIVE: The main objective of this study was to determine the amount and type of fat consumed by early school-age children per day. Dietary fat intake as a percentage of the total calorie intake was also estimated. METHODS: The study was conducted in Lublin, the largest city in south-east Poland, between January 2014 and April 2014, on 702 randomly selected children, i.e. 3% of the total population of early school-age children in the research area. The parents were asked to provide information about the type and amount of food consumed by their children daily. A standard food frequency questionnaire was used. RESULTS: Dietary levels of saturated fat were elevated in the analyzed populations and were the source of 13.33% of daily calorie intake. In the studied population, the ratio of saturated to monounsaturated and polyunsaturated fatty acids was determined at 3.25: 2.95: 1. Dietary intake of alpha-linolenic acid (ALA) reached 1.057 +/- 0.55 g (0.63% of daily calorie intake) on average, and dietary intake of linoleic acid (LA) was determined at 3.86 +/- 2.51 g (2.31% of daily calorie intake). CONCLUSIONS: The average total calorie intake of children aged 6-11 years was 1445.66 calories per day. Average fat intake was 29.64 % of the total calorie intake. The highest intake of SFAs was found in the youngest age group of 6- to 8-year-olds. The type of food consumed by children affected the amount and type of dietary fat in all age groups. PMID- 26870118 TI - Plasmodium Vivax causing acute kidney injury: A foe less addressed. AB - OBJECTIVE: To report patients developing acute kidney injury (AKI) after Vivax malaria. METHODS: An observational cohort of patients identified as having acute kidney injury (AKI) after Plasmodium vivax infection. AKI was defined according to RIFLE criteria with sudden rise in creatinine or decline in urine output or both. All patients had normal size non obstructed kidneys on ultrasonography, with no previous co morbids. Malarial parasite Vivax was seen on blood peripheral film in all patients. RESULTS: From January 1990 - December 2014, total 5623 patients with AKI were registered in our institute, of these 671 (11.93%) developed AKI in association with malarial infection, furthermore, Vivax was species in 109 patients. Average age of patients was 33.49+/-14.67 (range 8-78 years) with 66 male and 43 female. Oligo-anuria and vomiting were most common associated symptoms with fever. Renal replacement therapy required in 82 (75.22%) patients. Complete recovery was seen in 69 (63.30%), while 14 (12.84%) expired during acute phase of illness. Jaundice, thrombocytopenia, central nervous system involvement, mechanical ventilation requirement and hematuria were the factors significantly associated with high mortality. CONCLUSION: Malaria still causing significant morbidity and mortality in our part of world. Vivax malaria can present with hemolysis, thrombocytopenia and kidney failure in remarkable number of patients. PMID- 26870119 TI - Effects of early enteral micro-feeding on neonatal serum Vitamin D levels. AB - OBJECTIVE: To evaluate the effects of early enteral micro-feeding on neonatal serum vitamin D levels, and to analyze the application value of glutamine. METHODS: One hundred ninty neonates enrolled in intensive care unit were randomly divided into a treatment group and a control group (n=95) that were both given enteral and parenteral nutrition support. Meanwhile, the treatment group was fed formula milk containing 0.3 g/(kg.d) glutamine as enteral nutrition support for 14 days. RESULTS: The weight of the treatment group increased significantly faster than that of the control group did (P<0.05). The treatment group had significantly higher milk amount and calorie intake than those of the control group (P<0.05), and neonates in the treatment group who reached calorie intake of 50/80/100 kcal/kg/d were significantly younger (P<0.05). Meanwhile, the treatment group was significantly less prone to feeding intolerance than the control group (P<0.05). After 14 days of feeding, the serum motilin, gastrin and vitamin D levels of both groups all increased, with significant intra-group and inter-group differences. Such levels of the treatment group significantly exceeded those of the control group (P<0.05). CONCLUSION: Supplementing early enteral micro-feeding with glutamine promoted the absorption of neonatal routine nutrients and vitamin D, obviously regulated gastrointestinal hormones, and elevated weight as a result. PMID- 26870120 TI - Refractive errors in patients with newly diagnosed diabetes mellitus. AB - BACKGROUND AND OBJECTIVE: Diabetes mellitus is a complex metabolic disorder that involves the small blood vessels, often causing widespread damage to tissues, including the eyes' optic refractive error. In patients with newly diagnosed diabetes mellitus who have unstable blood glucose levels, refraction may be incorrect. We aimed to investigate refraction in patients who were recently diagnosed with diabetes and treated at our centre. METHODS: This prospective study was performed from February 2013 to January 2014. Patients were diagnosed with diabetes mellitus using laboratory biochemical tests and clinical examination. Venous fasting plasma glucose (fpg) levels were measured along with refractive errors. Two measurements were taken: initially and after four weeks. The last difference between the initial and end refractive measurements were evaluated. RESULTS: Our patients were 100 males and 30 females who had been newly diagnosed with type II DM. The refractive and fpg levels were measured twice in all patients. The average values of the initial measurements were as follows: fpg level, 415 mg/dl; average refractive value, +2.5 D (Dioptres). The average end of period measurements were fpg, 203 mg/dl; average refractive value, +0.75 D. There is a statistically significant difference between after four weeks measurements with initially measurements of fasting plasma glucose (fpg) levels (p<0.05) and there is a statistically significant relationship between changes in fpg changes with glasses ID (p<0.05) and the disappearance of blurred vision (to be greater than 50% success rate) were statistically significant (p<0.05). Also, were detected upon all these results the absence of any age and sex effects (p>0.05). CONCLUSIONS: Refractive error is affected in patients with newly diagnosed diabetes mellitus; therefore, plasma glucose levels should be considered in the selection of glasses. PMID- 26870121 TI - Influence of mouth rinses on the surface hardness of dental resin nano-composite. AB - OBJECTIVE: The aim of this research was to assess the effect of mouth rinses with and without alcohol on the hardness of dental nano-filled composite. METHODS: The micro-hardness of fifty circular disk shaped specimens of 7 mm x 2 mm were measured after 14 days. Specimens were immersed into alcohol containing (Listerine and Colgate Perioguard) and alcohol-free (Prodent and Sensodyne Oral antiseptic) mouth rinse solutions. Artificial saliva served as the control. Vickers Micro-hardness was measured with a 30gram load for 30 seconds dwell time by using a diamond indenter. Significant differences were represented by p<0.05, whereas highly significant difference represented by p<0.01. The level of significance (p) was calculated with the help of repeated measure ANOVA. For multiple comparisons, Tukey's multiple comparison test was used. RESULTS: Statistical analysis revealed highly significant difference between specimens immersed in artificial saliva (control) and Listerine (p<0.01). Whereas significant difference were observed between control and Colgate Periogard (p<0.05). However, no significant difference was observed on comparing Prodent and Sensodyne Oral antiseptic mouth rinses with control group(p>0.05). Control specimens depicted highest value of micro-hardness(60.5746 +/- 3.2703) compared to the lowest value seen in specimens immersed in Listerine solvent(54.4687 +/- 1.0937). CONCLUSION: Alcohol containing mouth rinsing solutions have more deleterious effect on hardness of nano composites as compared to alcohol-free mouth rinses. PMID- 26870122 TI - Effects of embolic agents with different particle sizes on interventional treatment of uterine fibroids. AB - OBJECTIVE: To compare the effects of embolic agents with different particle sizes on interventional treatment of uterine fibroids (UFs). METHODS: One-hundred and thirty patients with UFs were divided into a treatment group and a control group (n=65) by random draw. All patients were treated by uterine artery embolization, with the treatment group using 200 MUm polyvinyl alcohol (PVA) particles and the control group using 500 MUm PVA particles. RESULTS: The success rate of embolization was 100%. After intervention, the treatment group was significantly less prone to complications such as lower abdominal pain, fever, nausea, vomiting and bleeding than the control group (P<0.05). The follicle-stimulating hormone levels of both groups were similar before and after intervention, and there were also no significant inter-group differences. The uterine and UF volumes of both groups significantly decreased six months after intervention (P<0.05), and those of the treatment group were significantly lower (P<0.05). The two groups had similar physical function, role-physical, bodily pain and general health scores before intervention, but the treatment group scored significantly higher than the control group did six months after intervention (P<0.05). CONCLUSION: Interventional embolization can well treat UFs, without apparently affecting ovarian functions. Small-sized PVA particles can improve the quality of life by shrinking the uterus and UFs as well as by reducing the risks of complications. PMID- 26870123 TI - Comparison of two main treatment modalities for acute ankle sprain. AB - OBJECTIVE: Acute ankle sprains are one of the most common injuries in emergency departments. Immobilization is widely accepted as the basic treatment modality for acute ankle sprains; however, immobilization method remains controversial. In this study, we aimed to compare two treatment modalities: splint and elastic bandage for the management of acute ankle sprains. METHODS: This prospective study was conducted in the emergency department. Fifty-one consecutive patients who were admitted to the emergency department owing to the complaint of ankle sprain and who were treated with an elastic bandage or a splint were included in the study. After bone injury was ruled out, treatment choice was left to the on shift physicians' discretion. The extent of edema was evaluated before and after the treatment by using a small, graduated container filled with warm water. Volume differences were calculated by immersing both lower extremities in a container filled to a constant level. Pain was evaluated using the visual analogue scale. RESULTS: There were 25 patients in the elastic bandage group and 26 patients in the splint group. VAS scores of these groups before and after the treatment were similar. Although edema size before and after the treatment were similar between the groups, edema size reduction was significantly more in the elastic bandage group [p=0,025]. CONCLUSIONS: This study showed that treatment of acute ankle sprains with an elastic bandage was more effective than splint in reducing edema. Therefore, an elastic bandage could be preferred over a splint for the treatment of acute ankle sprains. PMID- 26870124 TI - Emergency contraception: Awareness, attitudes and barriers of Saudi Arabian Women. AB - OBJECTIVES: To assess knowledge, attitude, and barriers about emergency contraception (EC) among married women of child bearing age. METHODS: A quantitative cross-sectional study was conducted over a 6-month period, commencing in March 2013 at Family Practice Clinics of King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. Data was collected using a structured pretested questionnaire and analyzed using SPSS version 21.0 statistical software. RESULT: A total of 242 women were enrolled in the study. Only 6.2% (15/242) had some knowledge of EC and of these only two had ever used it. Health care professionals were the least reported source of EC information (6.6%, n=1). Majority (73.3%) had negative attitude toward EC being available over-the-counter without a prescription. The most common barriers to using EC were concerns about possible health effects. Only two women (13.3%) considered religious belief as a major hindrance to its use. CONCLUSION: Awareness of emergency contraception is very low among women of Saudi Arabia. Health care professionals were the least reported source of information, which is a cause for concern. Our findings reveal an urgent need to educate women about EC, keeping in view the social norms and the Islamic values. PMID- 26870125 TI - Comparison of frequency of insulin resistance in patients with chronic obstructive pulmonary disease with normal controls. AB - OBJECTIVE: To compare mean homeostatic model assessment of insulin resistance (HOMA-IR) in patients with and without chronic obstructive pulmonary disease (COPD). METHODS: A Case control analytic study was conducted in medical outpatient department of Medial Unit-II of Dow University of Health Sciences from April 2013 to September 2013. All patients with the diagnosis of COPD were included as cases. Controls were age match healthy individuals with minor illnesses. Age, weight, height and forced expiratory volume in one second to forced vital capacity (FEV1/FVC) ratio were documented. Fasting blood glucose and fasting insulin levels were done. Body mass index (BMI) and IR was calculated using the formulas. HOMA-IR was compared between cases and controls. RESULTS: Forty COPD patients were compared with thirty five age match controls. HOMA-IR was found to be higher in cases as compared to controls (2.85 v/s 2.00) with a p value <0.000. CONCLUSION: COPD is one of the chronic debilitating diseases in our region with various extra-pulmonary complications. We found IR to be present higher in COPD patients compared with healthy controls. Evaluating the pulmonary function as well as systemic metabolic parameters, may contribute to minimizing mortality and morbidity. PMID- 26870126 TI - Developing a novel risk-scoring system for predicting relapse in patients with ulcerative colitis: A prospective cohort study. AB - OBJECTIVES: Ulcerative Colitis (UC) follows a natural clinical course of relapses and remissions. The aim of this study was to construct a risk-scoring formula in order to enable predicting relapses in patients with UC. METHODS: From October 2012 to October 2013, 157 patients from Shiraz, southern Iran who were diagnosed with UC and in remission were enrolled. At 3-month intervals, multiple risk factors of hemoglobin, complete blood counts, serum iron and albumin, erythrocyte sedimentation rate, and faecal calprotectin levels, sex, age, cigarette smoking, positive family history of inflammatory bowel diseases, past history of appendectomy, extra-intestinal accompanying diseases, extent of disease at the beginning of study, number of previous relapses, duration of disease and duration of remission before the study were assessed. Univariate and multivariate logistic regression were applied to fit the final model. The new risk-scoring system accuracy was assessed using receiver-operating-characteristics (ROC) curve analysis. RESULTS: Seventy four patients (48.1%) experienced a relapse. Multivariate analysis revealed that relapses could significantly be predicted by the level of fecal calprotectin (OR=8.1), age (OR=9.2), the Seo activity index (OR=52.7), and the number of previous relapses (OR=4.2). The risk scoring formula was developed using the regression coefficient values of the aforementioned variables. CONCLUSION: Four predictor variables were significant in the final model and were used in our risk-scoring formula. It is recommended that patients who achieve high scores are diligently observed, treated, and followed up. PMID- 26870127 TI - Multiple cannulated screw fixation of young femoral neck fractures. AB - OBJECTIVE: We wanted to analyze the factors affecting the results of multiple cannulated screws fixation in patients less than 60 years old with femoral neck fracture (FNF). METHODS: We reviewed 52 patients (30 males, 22 females) who were treated with multiple cannulated screws fixation for FNFs. They were followed up for more than one year during January 2002 to December 2012. They were classified by Garden's classification. The anatomic reduction was evaluated by Garden's alignment index on hip both anteroposterior and lateral images. Postoperative complications were analyzed during follow up periods. RESULTS: By Garden's classification, 6 cases were in stage I, 13 cases in stage II, 30 cases in stage III and 3 cases in stage IV. During follow up periods, avascular necrosis of the femoral head was observed in 12 cases (23%) and nonunion was observed in 5 cases (9%). The 16 patients who had complications underwent total hip arthroplasty (31%). In non-displaced fracture groups (Garde I, II) did not have AVN nor nonunion. The incidence of complications in displaced fracture group was 51.5%. The complicated cases showed tendency for increased apex anterior angulation of femoral neck on hip lateral images and the result was statistically significant. (p=0.0260). CONCLUSION: The patients less than 60 years old who were treated with multiple cannulated screws fixation for displaced FNFs showed the incidence of complications was more than 50%. It needs a cautious approach for anatomical reduction, especially related to anterior angulation on hip lateral image. PMID- 26870128 TI - Increased Body Mass Index may lead to Hyperferritinemia Irrespective of Body Iron Stores. AB - OBJECTIVE: Obesity causes subclinical inflammation which results in the secretion of various bioactive peptides that are key players in metabolic regulation of iron homeostasis. We sought to establish correlation of one such peptide (ferritin) with marker of subclinical inflammation (CRP) in various BMI. METHODS: Total 150 subjects between the ages of 20-60 years were included in the cross sectional study conducted at Basic Medical Sciences Institute, Jinnah Post Graduate Medical Centre, Karachi, Pakistan. Body Mass Index (BMI) was calculated by weight (kg) /height (m(2)). The given values were used as reference for Group A: normal weight (18.0-22.9 kg/m2), Group B: overweight (23.0-24.9 kg/m2), Group C: obese (>25.0 kg/m2) according to South Asian criteria. Serum Iron, Total Iron Binding Capacity, serum Transferrin Saturation, serum Ferritin and C-reactive protein were measured by commercially available kits. ANNOVA with Tukey's minimum significant difference and Spearman Rho correlation were used considering p<0.05 significant. RESULTS: The results identified an increased serum Ferritin and CRP in obese versus lean subjects (p < 0.001). BMI showed significantly positive correlation with serum CRP (r = 0.815; p-value < 0.01) and Ferritin (r = 0.584; p value < 0.01). However, serum Iron levels and Transferrin saturation decreased in obese versus normal weight individuals (p < 0.001). CONCLUSION: This integrated new data reveals that individuals with high BMI had high levels of Serum Ferritin despite low levels of iron with high levels of C- reactive protein. This might be caused due to inflammatory conditions prevailing in the presence of increased adipose tissue. PMID- 26870129 TI - Is it possible to objectify the visual pain scale? AB - OBJECTIVES: To test our hypothesis that a new modified VAS (mVAS) is superior and more objective than VAS in evaluating pain perception and treatment response between genders who have renal colic pain. METHODS: The individuals in patient and control groups were first asked to mark the pain perceived during access of IV line (VASIV score). Then the patients with renal colic were asked to mark the pain they experienced before treatment (VASRC score) and at 15 and 30 minutes after the administration of the first analgesic drug. The modified VAS scores (mVAS score) were obtained by subtracting the VASIV score from VASRC score. RESULTS: When VAS was used, the female patients had significantly higher level of pain at 0, 15, and 30(th) minutes than men (p = 0.012, p = 0.001, and p = 0.003, respectively). However, there was not any significant difference at 0 and 30(th) min between sexes while female patients had significantly higher level of pain scores only at 15(th) minute according to mVAS scores (p = 0.027). CONCLUSION: We think that the mVAS is superior and more objective than VAS in evaluating pain perception and abolished the difference in the perceived level of pain due to gender. PMID- 26870130 TI - Packed cell volume Platelet count, PT, PTTK and Fibrinogen concentration of HIV positive patients on antiretroviral drugs. AB - OBJECTIVE: This is aimed at investigating some coagulation and haematologic profile of HIV positive patients on highly active antiretroviral therapy in patients attending clinic at the University of Benin Teaching Hospital. METHODS: This is a correlation study comprising fifty (50) HIV positive patients on HAART between 6 - 12 months as test subjects and fifty (50) HIV positive patients who have not began HAART as control subjects. Five millilitres of blood was withdrawn from each group by venepuncture into ethylene diaminetetracetic and sodium citrate anticoagulant containers. Platelet counts were estimated manually using ammonium oxalate solution, packed cell volume by the microhaematocrit method while Prothrombin Time (PT), Activated partial thrombroplastin time and fibrinogen concentration were done by methods described by Monica Chessbrough. RESULTS: This is presented as mean +/- standard error of mean. There were reduction in PCV and platelet count between test and control subjects although not statistically significant (P> 0.05) while there was a significant increase in PT and PTTK between test and control groups (P<0.05). No significant change was observed in fibrinogen concentration in HIV patients on HAART and those not on HAART. CONCLUSION: HAART increases PT and PTTK in HIV infection. PMID- 26870131 TI - Perception of content and non-content expert facilitators of PBL according to students' performance levels. AB - OBJECTIVE: Problem-based learning (PBL) is a student-centred learning system that involves multidisciplinary fields focused on problem solving. Facilitators of PBL are not necessarily content experts but little is known on how this concept has affected the outcomes of PBL sessions in learning Medical Biochemistry. We aimed to evaluate the impact of having the content expert as a facilitator in conducting PBL. METHODS: A total of 150 first and second year medical students from the University Kebangsaan Malaysia were interviewed with a validated set of questions to acquire their views on the roles of facilitators in PBL in learning Medical Biochemistry. Their achievement were evaluated through their essay marks derived from various PBL packages. RESULTS: All respondents agreed that PBL sessions associated with Medical Biochemistry are best appreciated when conducted by a content-expert facilitator. Their exam marks reflected well on their perception. CONCLUSION: PBL sessions related to Medical Biochemistry is best facilitated by Biochemistry lecturers as the content experts. PMID- 26870132 TI - Recurrent mutation in CDMP1 in a family with Grebe chondrodysplasia: broadening the phenotypic manifestation of syndrome in Pakistani population. AB - Grebe syndrome (OMIM-200700) is a very rare type of acromesomelic dysplasia with autosomal recessive inheritance. We studied a Pakistani family with two affected individuals having typical features of Grebe chondrodysplasia. Patients were observed with short and deformed limbs having a proximo-distal gradient of severity. Hind-limbs were more severely affected than fore-limbs. Digits on autopods were very short and nonfunctional. Index subject also had nearsightedness. However, symptoms in the craniofacial and axial skeleton were minimal. Genetic analysis revealed four base pair insertion mutation (c.1114insGAGT) in gene coding cartilage-derived morphogenetic protein-1 (CDMP1). This mutation was predicted to cause premature stop codon. The clinical presentation in this study broadens the range of phenotypes associated with CDMP1 mutation in Pakistani population. PMID- 26870133 TI - Pulmonary renal syndrome in a patient with vasculitis: Case report and review of literature. AB - Granulomatosis with polyangiitis (GPA) previously known as Wegner's granulomatosis, is a small vessel vasculitis that preferentially involves capillaries, arterioles and venules, presenting as multisystemic disease classically with alveolar haemorrhage and renal insufficiency. We report a case of GPA diagnosed on history, clinical findings and supported by imaging and very high levels of C-ANCA. Renal biopsy confirmed the typical histopathological findings. We discuss herein the management of the case and review of literature. PMID- 26870134 TI - Disorders associated with malabsorption of iron: A critical review. AB - Malabsorption is a disorder of the gastrointestinal tract that leads to defective digestion, absorption and transport of important nutrients across the intestinal wall. Small intestine is the major site where most of the nutrients are absorbed. There are three main mechanisms of malabsorption; premucosal, mucosal and postmucosal. Premucosal malabsorption is the inadequate digestion due to improper mixing of gastrointestinal enzymes and bile with chyme. This could be because of surgical resection of the small intestine or a congenital deficiency of the enzymes and bile responsible for digestion e.g. postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis etc. Mucosal malabsorption occurs in celiac disease, tropical sprue, Crohn's disease etc. Postmucosal condition arises due to impaired nutrients transport e.g. intestinal lymphangiectasia, macroglobulinemia etc. Disorders of malabsorption lead to decreased iron absorption and produce iron deficiency anemia. Using the index terms malabsorption, postgastrectomy, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gallstones, cholangitis, celiac disease, tropical sprue, Crohn's disease intestinal lymphangiectasia, macroglobulinemia and iron deficiency anemia the MEDLINE and EMBASE databases were searched. Additional data sources included bibliographies and references of identified articles. PMID- 26870135 TI - Outcome of pediatric procedural sedation & analgesia in a tertiary care hospital in Pakistan. AB - BACKGROUND AND OBJECTIVE: Procedural sedation and analgesia (PSA) is pharmacologically induced state which allows patients to tolerate painful procedures while maintaining protective reflexes. It is the standard of care but there is limited data from Pakistan. Our objective was to assess the safety of the procedural sedation and analgesia in pediatric population at a tertiary care setting. METHODS: A retrospective notes and record review was conducted at the Aga Khan University Hospital, Karachi over 4 years from April 2010 to August 2014. Patients were between ages 6 months to 16 years and were in low risk category. The combination of Ketamine and Propofol were used. Data collected on the standardized hospital PSA form. All procedures were performed by two trained persons. RESULTS: A total of 3489 diagnostic and therapeutic procedures were performed. Satisfactory level of sedation was achieved for 3486 (99%) of procedures. Adverse events occurred in 21 (0.6%) patients including: 12 (0.3%) episodes of hypoxia, 07 (0.2%) episodes of apnea, 02 (0.06%) episodes of post sedation hallucination. No major events were noted. CONCLUSION: Procedural sedation & analgesia for children using Propofol and Ketamine is found safe and effective in our setting. PMID- 26870136 TI - The bread and butter of statistical analysis "t-test": Uses and misuses. PMID- 26870137 TI - Etiological and clinical characteristics of central diabetes insipidus in children: a single center experience. AB - BACKGROUND: Central diabetes insipidus (CDI) results from a number of conditions affecting the hypothalamic-neurohypophyseal system to cause vasopressin deficiency. Diagnosis of CDI is challenging, and clinical data and guidelines for management are lacking. We aim to characterize clinical and radiological characteristics of a cohort of pediatric patients with CDI. METHODS: A chart review of 35 patients with CDI followed at North Carolina Children's Hospital from 2000 to 2015 was undertaken. The frequencies of specific etiologies of CDI and characteristic magnetic resonance imaging (MRI) findings were determined. The presence of additional hormone deficiencies at diagnosis and later in the disease course was ascertained. Patient characteristics and management strategies were evaluated. RESULTS: The cohort included 14 female and 21 male patients with a median age of 4.7 years (range, less than 1 month to 16 years) at diagnosis. Median duration of follow-up was 5 years (range, 2 months to 16 years). The cause of CDI was intracranial mass in 13 patients (37.2 %), septo-optic dysplasia in 9 patients (25.7 %), holoprosencephaly in 5 patients (14.2 %), Langerhans cell histiocytosis in 3 patients (8.6 %), isolated pituitary hypoplasia in 2 patients (5.7 %), and encephalocele in 1 patient (2.9 %). Patients were symptomatic for a mean of 6.3 months (range, less than 1 month to 36 months) prior to diagnosis of CDI. Growth hormone (GH), thyrotropin (TSH), adrenocorticotropic hormone (ACTH), and gonadotropin deficiencies were present at diagnosis in 34, 23, 23, and 6 % of patients, respectively. GH, TSH, ACTH, and gonadotropin deficiencies were diagnosed during follow-up in 23, 40, 37, and 14 % of patients, respectively. In patients with structural CNS abnormalities, development of additional hormone deficiencies occurred anywhere from 2 months to 13 years after the time of initial presentation. CONCLUSIONS: All patients in our cohort had an underlying organic etiology for CDI, with intracranial masses and CNS malformations being most common. Therefore, MRI of the brain is indicated in all pediatric patients with CDI. Other pituitary hormone deficiencies should be investigated at diagnosis as well as during follow-up. PMID- 26870139 TI - Clinco-Pathological Patterns in Women with Dysfunctional Uterine Bleeding. AB - BACKGROUND: The term dysfunctional uterine bleeding (DUB) refers to any abnormal bleeding from the uterus, unassociated with tumour, inflammation and pregnancy. The histological diagnosis of DUB is very essential for adequate management especially in perimenopausal and postmenopausal females. The present study was undertaken with the aim of evaluating DUB in various age groups, carry out histopathological study of the endometrium and analyze its clinic-pathological patterns. METHODS: The study included 500 cases of atypical uterine bleeding, out of which 120 cases of DUB were included based on clinical features and detailed investigations. Study was conducted in Jawaharlal Nehru Medical College, Aligarh Muslim University, between March 2003 to December 2004 Endometrial tissue was collected by D&C procedure and the samples were sent for histopathological evaluation by pathologist. RESULT: Hyperplasia was the commonest endometrial pathology (20.5%) followed by luteal phase insufficiency (15.6%) and secretory endometrium (13.7%). Endometritis including tubercular endometritis (12.7%), post abortal (5.8%), proliferative (6.8%), polyp (3.9%), atrophic (3.9%), exogenous hormone changes (2.9%) and anovulatory cycles (6.8%) made up for the remaining lesions. CONCLUSION: DUB occurs secondary to a wide variety of functional and structural abnormalities, warranting a thorough evaluation especially in perimenoupausal females. Menorrhagia is a common symptom and the most likely etiology relates to the patient's age. Significant number of endometrial samples revealed pathology rendering endometrial curetting and biopsy an important procedure. Cervical cytology is a valuable adjunct however histopathology remains the gold standard in diagnosis. PMID- 26870138 TI - Thyroid Papillary Microcarcinoma: Etiology, Clinical Manifestations,Diagnosis, Follow-up, Histopathology and Prognosis. AB - BACKGROUND: Thyroid carcinoma is the most common malignancy of the endocrine system. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for 70-90% of well-differentiated thyroid malignancies. Thyroid papillary microcarcinoma is a subtype of papillary carcinoma that included tumors with less than 10mm diameter. As a result of diagnostic methods improvement, prevalence of this tumor is increasing. In this study we reviewed different characteristics of tumor. METHODS: We searched various factors about this tumor in different databases (PubMed, Ovid, Google scholar, Iran medex and SID databases, from July 2012 until August 2013), after that, the articles were classified. Data of each article were extracted and sorted in tables. Data of each factor in different articles were summarized. RESULTS: Etiology, clinical presentation, prognosis, histopathology, follow-up, diagnosis and also age, gender, tumor size and treatment were factors about this tumor described in details here. CONCLUSION: Awareness and better understanding of the characteristics of this tumor and manage it as an individual and valuable tumor can take an effective step in promoting public health practice. PMID- 26870140 TI - Clinical Characteristic of the HIV/AIDS Patients with Cryptosporidiosis Referring to Behavioral Diseases Consultation Center, Imam Khomeini Hospital, Tehran in 2013. AB - BACKGROUND: Cryptosporidium is known as an opportunist disease-causing agent in man in recent decades. It causes diarrhea and intestinal disorders in the immune deficit and immune competent individuals. This study was aimed to investigate the clinical characteristics of HIV/AIDS patients with cryptosporidiosis infection. METHODS: This cross-sectional descriptive study was performed on 53 HIV/AIDS patients referred to the Behavior Disease Consultation Center of Imam Khomeini Hospital in Tehran, Iran in 2013. First, the patients were studied clinically and the context data were recorded in a questionnaire for parasitological examination and referred to the laboratory for eosinophil count, and CD4 count per ml of blood. RESULTS: Cryptosporidiosis was observed in 4 (7.6%) of the total 53 HIV/AIDS patients. The highest prevalence of infection was observed in the age range of 30-39 yr. It was observed in different sexes as 5.7% of male and 1.9% of female, but statistically was insignificant (P=0.163).75% of patients had no intestinal symptom, 11.4% with acute diarrhea and 3.8% with chronic diarrhea. Cryptosporidiosis cases were observed in 5.7% of patients without intestinal symptom. CONCLUSION: Practitioners in the clinical examination for the detection of the opportunistic intestinal protozoan infection should use clinical and paraclinical characteristics of the HIV/AIDS patients for the diagnostic of Cryptosporidium and other opportunistic parasitic diseases. PMID- 26870141 TI - Enzymatic Digestion Pattern of Varicella Zoster Virus ORF38 and ORF54 in Chickenpox Patients Using RFLP Technique. AB - BACKGROUND: Varicella zoster virus (VZV) causes chickenpox in children and zoster (zona) in the elderly. Using RFLP-PCR method for detection of VZV specific SNPs ORF38, 54 and 62 could distinguish the profile of VZV isolates. The aim of this study was to investigate enzymatic digestion pattern of VZV ORF38 and ORF54 in chickenpox patients using RFLP technique. METHODS: Thirty-eight chickenpox patients, who referred to the hospitals of Iran University of Medical Sciences in Tehran from May 2010 to June 2015 were enrolled in this cross sectional study. After the DNA extraction, PCR amplification of 38 VZV isolates performed by specific primers of ORFs 38 and 54, then RFLP assay and digestion carried out by PstI (for ORF38) and BglI (for ORF54) restriction enzymes. RESULTS: Of 38 positive VZV DNA, the mean age (yr)+/-SD was 34.4+/-23.3 (range: 7-89). 22 (57.9%) were female and 16 (42.1%) were male. The predominant VZV profile of BglI(+) PstI(+) were 89.5% (34/38) followed by 10.5% (4/38) PstI(+) BglI?. Statistical analysis showed that there was no significant relationship between genotype, age, sex, and year of infection variables (P value> 0.05). The common VZV genotype among Iranian patients with chickenpox and zona infection is genotype BglI(+) PstI(+) followed by PstI(+) BglI?. CONCLUSION: There are different VZV circulating genotypes that call for for more research on this field by widely population and other methods such as nucleotide sequencing to justify the accurate VZV genotype prevalence in Iran. PMID- 26870142 TI - Developing Michigan Cancer Foundation 7 Cells with Stable Expression of E7 Gene of Human Papillomavirus Type 16. AB - BACKGROUND: Human papillomavirus (HPV) is responsible for the development of cervical neoplasia. Infection with human papillomavirus type 16 (HPV-16) is a major risk factor for the development of cervical cancer. The virus encodes three oncoproteins (E5, E6 and E7), of which, the E7 oncoprotein is the major protein involved in cell immortalization and transformation of the infected cells. The aim of the current study was to develop Michigan Cancer Foundation 7 (MCF7) cells, which could stably express E7 protein of HPV type 16. METHODS: E7 gene of HPV type 16 was introduced into MCF7 cells by Lipofectamine 2000 reagent and the transfected cells were treated with G418 antibiotic. After antibiotic selection of the transfected cells, stable expression of E7 gene of HPV16 was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Antibiotic selections of transfected cells were performed and transfected cells were alive in cytotoxic concentration of the antibiotic. RNA was extracted from transfected cells and E7 gene of HPV16 was amplified by RT-PCR method and a 350-bp band corresponds to E7 was observed. CONCLUSION: Results confirmed the stable transfection of cells. The stably transfected cells can be used as a useful tool in future studies on HPV16 and cancers caused by this virus. PMID- 26870143 TI - Relation between Resistance to Antipseudomonal beta-Lactams and ampC and mexC Genes of Pseudomonas aeruginosa. AB - BACKGROUND: In order to select a better antibiotic choice for treatment of Pseudomonas aeruginosa infections, this study was conducted to determine the frequency of resistance to some antipseudomonal beta-lactams in P. aeruginosa isolates from patients in Tehran, Iran. In addition, the relation between presence of genes known to be responsible for resistance to beta-lactams (ampC, mexC 1,2, and mexC 3,4 genes) and resistance phenotype among P. aeroginosa isolates was evaluated. METHODS: P. aeruginosa strains were isolated and identified by routine methods and PCR for oprL gene. Disk diffusion method was employed to determine the antimicrobial susceptibility pattern according to CLSI recommendations. PCR was used to detect the resistance genes. RESULTS: Among 100 isolates of P. aeruginosa, 82% had ampC, 86% mexC 1,2 and 89% mexC 3,4 genes and combinations of these genes were seen in most of isolates and only 3% of isolates had none of these genes. Resistance to mezlocillin, cefepime, ceftazidime and piperacillin/ tazobactam was seen in 46%, 41%, 36% and 29% of isolates, respectively. Significant relation (P value <=0.05 by Chi-square or Fisher Exact test) was observed between the presence of ampC gene and resistance to all the studied beta-lactams in this study. No relation was observed for mexC genes, although many of isolates containing these two genes were phenotypically resistant. DISCUSSION: This study had shown for the first time, the presence of ampC and mexC genes in significant percent of clinical isolates of P. aeruginosa in Tehran, Iran, and relation between presence of ampC gene and resistance to beta-lactams. PMID- 26870144 TI - Clinico-Pathological Study of Cutaneous Granulomatous Lesions- a 5 yr Experience in a Tertiary Care Hospital in India. AB - BACKGROUND: Granulomatous dermatoses are common skin pathology, often need histopathological confirmation for diagnosis. Histologically six sub-types of granulomas found in granulomatous skin diseases- tuberculoid, sarcoidal, necrobiotic, suppurative, foreign body & histoid type. The aims of the present study were clinico-pathological evaluation of granulomatous skin lesions and their etiological classification based on histopathological examination. METHODS: It was a five years (Jan 2009- Dec 2013) retrospective study involving all the skin biopsies. Detailed clinical and histopathological features were analyzed and granulomatous skin lesions were categorized according to type of granuloma & etiology. Special stains were used in few cases for diagnostic purpose. RESULTS: Among 1280 skin biopsies, 186 cases (14.53%) were granulomatous skin lesions with a ratio 1:24. In histopathological sub-typing, tuberculoid granuloma was most common type (126 cases, 67.74%). Most common etiology of granuloma in the study was leprosy (107 cases, 57.52%). Other etiologies were cutaneous tuberculosis, foreign body granulomas, fungal lesions, cutaneous leishmaniasis, sarcoidosis and granuloma annulare. CONCLUSION: Histopathology is established as gold standard investigation for diagnosis, categorization and clinico-pathological correlation of granulomatous skin lesions. PMID- 26870145 TI - Ovarian Hemangioma: a Rare Case Report and Review of the Literature. AB - Ovarian hemangiomas are benign and rare tumors of female genital tract with less than 60 reported cases in the literature. A 38- yr- old woman was admitted to Be'sat Hospital, Tehran, Iran in 2012, due to severe abdominal pain. Ultrasound evaluation revealed a 6 cm left ovarian cystic mass and serum tumor markers were normal. Then, left salpingo-oophorectomy was performed for the patient. Microscopic examination revealed a follicular cyst and an incidental cavernous hemangioma consisting thin-walled vascular channels filled with blood that lined with flatten endothelial cells. In IHC staining strong immunoreactivity for CD31 and CD34 were seen, finally, the diagnosis of primary ovarian hemangioma, cavernous-type was made. The clinicopathologic presentation of this unusual benign tumor is discussed. PMID- 26870146 TI - Immature Teratoma with Embryonal Carcinoma; a Rare Malignant Mixed Germ Cell Tumor in a 13-Year-Old Girl. AB - Malignant mixed germ cell tumors,though rare overall, are the most common type of malignant ovarian neoplasms in young and adolescent girls. These tumors are rapidly growing and can metastasize. We report a case of 13-yr-old girl who presented at SHKM GMC, Nalhar, Mewat, Haryana, India in December 2013 with huge abdominal lump of a malignant mixed germ cell tumor comprising both immature teratoma and embryonal carcinoma. This report illustrates the aggressiveness of this tumor and emphasises the need of early diagnosis and treatment. PMID- 26870147 TI - The Report of KRAS Mutation and NRAS Wild Type in a Patient with Thyroid Metastasis from Colon Cancer: a Rare Case Report. AB - Colorectal cancer (CRC) metastasis to the thyroid gland is rare. Here we report a 45 yr-old man in western Iran referred to Hematology Clinic, Kermanshah City, Iran in March 2014 with complaint of exertional dyspnea, multi-nodular goiter as well as complaint of exertional dyspnea, and multi-nodular goiter. His history included a low anterior resection of rectum in 9 months ago for a high-risk stage II rectal adenocarcinoma. He did not show clinical signs of hyperthyroidism other than thyroid enlargement. In thyroid nodule the FNA cytology, pathology reported anaplastic thyroid malignancy. Pathologists reported final diagnosis of colorectal metastasis of thyroid gland. Then due to metastatic pattern of disease, his pathology was evaluated for RAS molecular assay. In the patients of metastatic CRC, RAS testing is the first step to identify those patients that could benefit from anti-EGFR monoclonal antibodies treatment. PMID- 26870148 TI - Solitary Psoas Muscle Metastasis of Gastroesphageal Junction Adenocarcinoma. AB - Metastasis of gastroesphageal junction (GEJ) adenocarcinoma in skeletal muscle is rare and primary sites for skeletal muscle metastases are usually lung, renal and colorectal cancer. We have encountered with the first case report of solitary psoas muscle metastasis of GEJ adenocarcinoma. Here we describe a 65 years old man was diagnosed with GEJ adenocarcinoma in Gastroenterology Department, Imam Hussein Hospital, Tehran, Iran in February 2014. We were not able to use PET techniques due to lack of access. Staging CT scans demonstrated a small mass lateral to right psoas muscle. A CT-guided core needle biopsy of right psoas muscle was performed that supported a diagnosis of adenocarcinoma consistent with primary adenocarcinoma of the GEJ. Distant metastasis to skeletal muscle rarely occurs in patients with GEJ adenocarcinoma, but heightened awareness to these soft tissue lesions is warranted. CT or MR imaging could show findings suggestive of metastatic disease, although PET is preferable modality. PMID- 26870149 TI - Congenital Anaplastic Rhabdomyosarcoma Presenting As Abdominal Wall Mass. AB - Rhabdomyosarcoma encompasses a group of malignant myogenic neoplasms expressing a multitude of clinical and pathological diversities. It is the commonest soft tissue sarcoma of childhood but neonates are rarely affected. Embryonal subtype is the most frequent. Head-neck and genitourinary tracts are predominant sites, while trunk is considered among the unusual sites of rhabdomyosarcoma. Herein we report a case of anaplastic rhabdomyosarcoma in a newborn girl presenting, at the Pediatric Surgery Outpatient Department of North Bengal Medical College and Hospital, India in 2013 with a large tumor mass in the left flank region, arising from abdominal wall muscles. PMID- 26870150 TI - Sarcomatoid Transrormation of Chromophobe Renal Cell Carcinoma. PMID- 26870151 TI - Drivers of hibernation in the brown bear. AB - BACKGROUND: Hibernation has been a key area of research for several decades, essentially in small mammals in the laboratory, yet we know very little about what triggers or ends it in the wild. Do climatic factors, an internal biological clock, or physiological processes dominate? Using state-of-the-art tracking and monitoring technology on fourteen free-ranging brown bears over three winters, we recorded movement, heart rate (HR), heart rate variability (HRV), body temperature (Tb), physical activity, ambient temperature (TA), and snow depth to identify the drivers of the start and end of hibernation. We used behavioral change point analyses to estimate the start and end of hibernation and convergent cross mapping to identify the causal interactions between the ecological and physiological variables over time. RESULTS: To our knowledge, we have built the first chronology of both ecological and physiological events from before the start to the end of hibernation in the field. Activity, HR, and Tb started to drop slowly several weeks before den entry. Bears entered the den when snow arrived and when ambient temperature reached 0 degrees C. HRV, taken as a proxy of sympathetic nervous system activity, dropped dramatically once the bear entered the den. This indirectly suggests that denning is tightly coupled to metabolic suppression. During arousal, the unexpected early rise in Tb (two months before den exit) was driven by TA, but was independent of HRV. The difference between Tb and TA decreased gradually suggesting that bears were not thermoconforming. HRV increased only three weeks before exit, indicating that late activation of the sympathetic nervous system likely finalized restoration of euthermic metabolism. Interestingly, it was not until TA reached the presumed lower critical temperature, likely indicating that the bears were seeking thermoneutrality, that they exited the den. CONCLUSIONS: We conclude that brown bear hibernation was initiated primarily by environmental cues, but terminated by physiological cues. PMID- 26870152 TI - Multivitamins and minerals modulate whole-body energy metabolism and cerebral blood-flow during cognitive task performance: a double-blind, randomised, placebo controlled trial. AB - BACKGROUND: The brain is by far the most metabolically active organ in the body, with overall energy expenditure and local blood-supply closely related to neural activity. Both energy metabolism and cerebral vaso-dilation are dependent on adequate micronutrient status. This study investigated whether supplementation with ascending doses of multi-vitamin/minerals could modulate the metabolic and cerebral blood-flow consequences of performing cognitive tasks that varied in difficulty. METHODS: In this randomised, double-blind, placebo-controlled, parallel-groups study 97 healthy females (25-49 y), who were not selected on the basis of any nutritional parameters, received either placebo or one of two doses of multivitamins/minerals. Cerebral blood-flow (CBF) parameters in the frontal cortex, and total energy expenditure (TotalEnergy), carbohydrate and fat oxidation (CarbOxi/FatOxi), were measured during 5 tasks of graded cognitive difficulty and a control task (5 min per task) using Near-infrared spectroscopy (NIRS) and Indirect calorimetry of exhaled pulmonary gas (ICa) respectively. Assessments took place 60 min after the first dose and following eight weeks supplementation. RESULTS: During task performance supplementation with the first dose of micronutrients led to a dose-dependent increase in TotalEnergy and FatOxi throughout the post-dose assessment period following the higher dose, and increases in the total concentration of haemoglobin, a proxy measure for CBF, during task performance following the lower dose of vitamins/minerals (also containing coenzyme-Q10). Chronic supplementation over 8 weeks led to a dose dependent increase in TotalEnergy during the task period. There were no interpretable effects on mood or cognitive performance. CONCLUSIONS: These results show that acute supplementation with micronutrients in healthy adults can modulate metabolic parameters and cerebral blood flow during cognitive task performance, and that the metabolic consequences are sustained during chronic supplementation. These findings suggest that both brain function and metabolism are amenable to micronutrient supplementation, even in adults who are assumed to have nutritional status typical of the population. TRIAL REGISTRATION: ClinicalTrials.gov - NCT02381964. PMID- 26870154 TI - Whole-Exome Sequencing Identifies Novel Somatic Mutations in Chinese Breast Cancer Patients. AB - Most breast cancer genomes harbor complex mutational landscapes. Somatic alterations have been predominantly discovered in breast cancer patients of European ancestry; however, little is known about somatic aberration in patients of other ethnic groups including Asians. In the present study, whole-exome sequencing (WES) was conducted in DNA extracted from tumor and matched adjacent normal tissue samples from eleven early onset breast cancer patients who were included in the Shanghai Breast Cancer Study. We discovered 159 somatic missense and ten nonsense mutations distributed among 167 genes. The most frequent 50 somatic mutations identified by WES were selected for validation using Sequenom MassARRAY system in the eleven breast cancer patients and an additional 433 tumor and 921 normal tissue/blood samples from the Shanghai Breast Cancer Study. Among these 50 mutations selected for validation, 32 were technically validated. Within the validated mutations, somatic mutations in the TRPM6, HYDIN, ENTHD1, and NDUFB10 genes were found in two or more tumor samples in the replication stage. Mutations in the ADRA1B, CBFB, KIAA2022, and RBM25 genes were observed once in the replication stage. To summarize, this study identified some novel somatic mutations for breast cancer. Future studies will need to be conducted to determine the function of these mutations/genes in the breast carcinogenesis. PMID- 26870153 TI - Quantum Coherence in Photosynthesis for Efficient Solar Energy Conversion. AB - The crucial step in the conversion of solar to chemical energy in Photosynthesis takes place in the reaction center where the absorbed excitation energy is converted into a stable charge separated state by ultrafast electron transfer events. However, the fundamental mechanism responsible for the near unity quantum efficiency of this process is unknown. Here we elucidate the role of coherence in determining the efficiency of charge separation in the plant photosystem II reaction centre (PSII RC) by comprehensively combining experiment (two dimensional electronic spectroscopy) and theory (Redfield theory). We reveal the presence of electronic coherence between excitons as well as between exciton and charge transfer states which we argue to be maintained by vibrational modes. Furthermore, we present evidence for the strong correlation between the degree of electronic coherence and efficient and ultrafast charge separation. We propose that this coherent mechanism will inspire the development of new energy technologies. PMID- 26870155 TI - Study of the occurrence of intra-abdominal hypertension and abdominal compartment syndrome in patients of blunt abdominal trauma and its correlation with the clinical outcome in the above patients. AB - BACKGROUND: Intra-abdominal pressure (IAP) measurements have been identified as essential for diagnosis and management of both intra-abdominal hypertension (IAH) and Abdominal compartment syndrome (ACS). It has gained prominent status in ICUs worldwide. We aimed to evaluate the utility of measurement of rise in bladder pressure to assess IAP levels in blunt abdominal trauma (BAT) patients. PATIENTS AND METHODS: Thirty patients of BAT with solid organ injuries were included in this study. Intra-abdominal pressure was measured through a Foleys bladder catheter throughout their stay. Bladder pressure was compared with clinical parameters like mean arterial pressures(MAP), respiratory rate(RR), serum creatinine(SC) and abdominal girth(AG) and also with outcome in terms of intervention whether operative(OI) or non-operative(NOI). RESULTS: Bladder pressure showed significant correlation with MAP (R = -0.418; P = 0.022), AG (R = 0.755; P = 0.000), SC (R = 0.689; P = 0.000) and RR (R = 0.537; P = 0.002). Bladder pressure (R = 0.851; P = 0.000), SC (R = 0.625; P = 0.000), MAP (R = 0.350; P = 0.058) and maximum AG difference (R = 0.634; P = 0.000) showed significant correlation with intervention. In total, 17 patients (56 %) required intervention, 9 patients (30 %) underwent NOI (pigtailing or aspiration) while 8 (27 %) needed OI. More than 3 derailed parameters were associated with 100 % intervention (Mean 3.47, SD-1.23). High APACHE III score on admission (>40) was associated with increased intervention (p = 0.001). Intervention correlates well with Grade of injury (p = 0.000) and not with number of organs injured (p = 0.061). Blood transfusion of 2 or more units of blood was associated with increased intervention (p = 0.000). CONCLUSION: Increased bladder pressure and other clinical parameters (MAP, SC, RR and change in AG) correlates well with intervention. Elevated bladder pressure correlates well with other clinical parameters in patients with BAT. Bladder pressure, SC, MAP, RR and AG difference can be used to determine the group of patients that can be managed conservatively and those that would benefit with minimal intervention or exploration. During Non operative management (NOM) of patients with BAT and multiple solid organ injuries, IAP monitoring may be a simple and objective guideline to suggest further intervention whether NOI or OI. Although routine bladder pressure measurements will result in unnecessary monitoring of large number of patients it is hoped that patients with IAH can be detected early and subsequent ACS with morbid abdominal exploration can be prevented. However the criterion for non operative failure and the point of decompression needs further refinement to prevent an increase of nontherapeutic operations. PMID- 26870158 TI - Characteristics of non-diabetic foot ulcers in Western Sydney, Australia. AB - BACKGROUND: There are few studies investigating the characteristics, risk factors and socioeconomic status of patients with non-diabetic foot ulcers. The aim of this study was to explore the characteristics of non-diabetic foot ulcers in a large tertiary referral outpatient hospital setting in Western Sydney, Australia. METHODS: From 2011 to 2013, data from 202 patients with non-diabetic foot ulcers during their initial visit were retrospectively extracted for analysis from Westmead Hospital's Foot Wound Clinic Registry. Data including demographics, socioeconomic status and foot ulcer characteristics were recorded on a standardised data collection form. RESULTS: Demographics and physical characteristics were: 54 % male, median age 78 years [interquartile range (IQR): 64-87], median body mass index (BMI) of 23.8 kg/m(2) (IQR: 20-26.9), 35 % had loss of protective sensation and the median postcode score for socioeconomic status was 996 (IQR: 935-1034). Foot ulcer characteristics were: median cross sectional area of 1.2 cm(2) (IQR: 0.3-5.0), 30.5 % plantar and 27 % dorsal, 22.1 % University of Texas (UT) Wound Classification for Diabetic Foot Ulcers Grade of 1C-3C (with ischaemia). CONCLUSIONS: Unlike diabetic foot ulcers, non-diabetic foot ulcers largely affected older males and females. In accordance with diabetic foot ulcer characteristics, socioeconomic status was not related to non-diabetic foot ulcers in Western Sydney. Based on the findings of this study the epidemiological pattern of non-diabetic foot ulceration and its pathogenesis requires further investigation. PMID- 26870159 TI - Long-term release of a thiobenzamide from a backbone functionalized poly(lactic acid). AB - Hydrogen sulfide is emerging as a critically important molecule in medicine, yet there are few methods for the long-term delivery of molecules that degrade to release H2S. In this paper the first long-term release of a thiobenzamide that degrades to release H2S is described. A series of polymers were synthesized by the copolymerization of L-lactide and a lactide functionalized with 4 hydroxythiobenzamide. A new method to attach functional groups to a derivative of L-lactide is described based on the addition of a thiol to an alpha,beta unsaturated lactide using catalytic I2. This reaction proceeded under mild conditions and did not ring-open the lactone. The copolymers had molecular weights from 8 to 88 kg mol-1 with PDIs below 1.50. Two sets of microparticles were fabricated from a copolymer; the average diameters of the microparticles were 0.53 and 12 MUm. The degradation of the smaller microparticles was investigated in buffered water to demonstrate the slow release of thiobenzamide over 4 weeks. Based on the ability to synthesize polymers with different loadings of thiobenzamide and that thiobenzamide is a known precursor to H2S, these particles provide a polymer-based method to deliver H2S over days to weeks. PMID- 26870160 TI - Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer. AB - Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib. PMID- 26870162 TI - Endometriosis and breast cancer: A survey of the epidemiological studies. AB - Endometriosis is a chronic gynecological disease with a wide spectrum of clinical manifestations that affects approximately 10% of women of reproductive age. Recent reviews have demonstrated the connection between endometriosis and breast cancer, which represents the most frequently diagnosed female cancer and the most common cause of cancer-related mortality among women worldwide. The aim of this study was to conduct a survey of available published epidemiological studies indicating the association between endometriosis and breast cancer, and simultaneously to categorize the results based on the strength of the association, with the intention of the critical evaluation of the existing data. We performed a rigorous search of the PubMed/Medline database, using the key words 'endometriosis' and 'breast cancer' for all studies published in the English language until September 2015. We found 4 retrospective cohort studies, 4 case-control studies and 3 case-cohort studies that demonstrated a notable risk for developing breast cancer among women with endometriosis. By contrast, we also found 5 case-control studies, 1 prospective cohort study, 1 case-cohort study and 1 cross-sectional study that demonstrated a negative association between endometriosis and breast cancer. In conclusion, as regards the clarification of a 'robust' or 'weak' association between endometriosis and breast cancer, no definite conclusions could be drawn, due to the limited number of studies and the limitations of each of these studies. New well-designed, prospective cohort or randomized control trials with long-term follow-up are warranted in order to provide evidence-based clinical recommendations for proper counseling, screening and treatment strategies for patients with endometriosis, and hence to improve public health. PMID- 26870161 TI - Use of genetically engineered stem cells for glioma therapy. AB - Glioblastoma, the most common and most malignant type of primary brain tumor, is associated with poor prognosis, even when treated using combined therapies, including surgery followed by concomitant radiotherapy with temozolomide-based chemotherapy. The invasive nature of this type of tumor is a major reason underlying treatment failure. The tumor-tropic ability of neural and mesenchymal stem cells offers an alternative therapeutic approach, where these cells may be used as vehicles for the invasion of tumors. Stem cell-based therapy is particularly attractive due to its tumor selectivity, meaning that the stem cells are able to target tumor cells without harming healthy brain tissue, as well as the extensive tumor tropism of stem cells when delivering anti-tumor substances, even to distant tumor microsatellites. Stem cells have previously been used to deliver cytokine genes, suicide genes and oncolytic viruses. The present review will summarize current trends in experimental studies of stem cell-based gene therapy against gliomas, and discuss the potential concerns for translating these promising strategies into clinical use. PMID- 26870163 TI - CT pelvimetry and clinicopathological parameters in evaluation of the technical difficulties in performing open rectal surgery for mid-low rectal cancer. AB - The present study aimed to evaluate the predictive value of pelvic anatomical and clinicopathological parameters for use in the estimation of the likely technical difficulties that may be encountered when performing open rectal surgery for mid low rectal cancer. Sixty consecutive patients, undergoing open rectal surgery for mid-low rectal cancer were recruited between June 2009 and April 2014. All of the surgical procedures conducted, were low anterior resection (LAR) or abdominoperineal resection (APR). The operations were performed by the same surgeon and surgical team. Pelvic dimensions and angles were measured using three dimensional reconstruction of spiral computerized tomography (CT) images. Operative time and intraoperative blood loss were used as indicators of operative difficulty. The independent variables were pelvic anatomical and clinicopathological parameters, and the dependent variables were operative time and intraoperative blood loss. Univariate and multivariate analyses were performed in order to determine the predictive significance of these variables. The pelvis width was significantly wider in females than in males (P<0.05), while the sacrococcygeal bending degree was significantly greater in males than in females (P<0.05). No significant difference were detected between the pelvis depth of females and males (P>0.05). Multivariate analyses showed that body mass index (BMI), tumor height, lymph node metastasis, anteroposterior diameter of the pelvic inlet, anteroposterior diameter of the pelvic outlet, height of the pubic symphysis, the sacrococcygeal distance, sacrococcygeal-pubic angle and diameter of the upper pubis to the coccyx were the main factors affecting the operative time (all P<0.05), while the maximum diameter of the tumor was the primary factor affecting intraoperative blood loss (P<0.05). Between the two procedures, the clinicopathological parameters appeared to be more valuable for predicting difficulty in LAR, in which operative time was associated with tumor height and tumor staging (RC2=0.312; P<0.001). By contrast, the pelvic anatomical parameters appeared to be more valuable predictors of variation in APR, in which intraoperative blood loss was associated with the anteroposterior diameter of the mid-pelvis, the anteroposterior diameter of the pelvic outlet, the interspinous diameter, the depth of the sacral curvature and the sacropubic distance (RC2=0.608; P=0.002). BMI, tumor height and the maximum diameter of the tumor may be used to predict the operative difficulty in performing open rectal surgery for mid-low rectal cancer. In addition to the associated clinicopathological parameters, wider, shallower and less curved pelvises may make the greatest contribution to reducing operative time and intraoperative blood loss. Operative difficulty is likely to be increased in deeper and narrower pelvises, or in those with greater sacrococcygeal curvature. PMID- 26870164 TI - Obstructive hydrocephalus as a result of giant cell tumor of the thoracic spine: A case report. AB - Giant cell tumors (GCTs) are rare bone tumors that account for ~5% of all primary bone tumors. When GCTs occur in the spine, patients usually present with localized pain and neurological symptoms, such as radiating pain or hyperesthesia. In the current report, an unusual case of a GCT of the thoracic spine associated with hydrocephalus is described. A 48-year-old male presented with urinary retention, loss of sensation in the lower limbs and inability to walk. The patient eventually developed hydrocephalus combined with altered consciousness, indicated by an inability to follow simple commands. Magnetic resonance (MR) imaging demonstrated the presence of a soft tissue mass at the T2 level, and biopsy examination of the tissue confirmed that it was a GCT. The patient experienced a sudden loss of consciousness due to an acute episode of obstructive hydrocephalus. A ventriculoperitoneal shunting procedure was performed to treat the hydrocephalus, and the patient regained normal consciousness, although the paraplegia persisted. An MR examination performed 30 months following surgery demonstrated that the tumor size was stable, consistent with the slow growth that is characteristic of GCTs. Diagnosis of GCTs may be challenging, and relies on radiographic and histopathologic findings. Although rare, acute hydrocephalus as a result of GCTs should not be excluded from a differential diagnosis. PMID- 26870165 TI - Aberrant expression of hSef and Sprouty4 in endometrial adenocarcinoma. AB - Fibroblast growth factor (FGF) 2-mediated signaling of the mitogen-activated protein kinase/RAS/extracellular signal-regulated kinase 1/2 pathway is a critical modulator in angiogenesis and is therefore essential for the pathogenesis of endometrial carcinoma. Human similar expression to FGFs (hSef) and Sprouty4 have each been reported to be negative regulators of FGF signaling. The aim of the present study was to investigate the expression of hSef and Sprouty4 in human endometrial adenocarcinoma. Using immunohistochemistry analysis, the expression of hSef and Sprouty4 was detected in human endometrial adenocarcinomas. Increased hSef expression was found to be present in endometrial adenocarcinomas. In addition, decreased hSef expression was identified in the blood vessels of endometrial adenocarcinoma samples. However, the expression of Sprouty4 was downregulated in human endometrial adenocarcinoma. Aberrant expression of hSef and Sprouty4 are involved in the pathogenesis of human endometrial adenocarcinoma. PMID- 26870166 TI - Identification of potential therapeutic targets for papillary thyroid carcinoma by bioinformatics analysis. AB - The aim of the present study was to identify potential therapeutic targets for papillary thyroid carcinoma (PTC) and to investigate the possible mechanism underlying this disease. The gene expression profile, GSE53157, was downloaded from the Gene Expression Omnibus database. Only 10 chips, including 3 specimens of normal thyroid tissues and 7 specimens of well-differentiated thyroid carcinomas, were analyzed in the present study. Differentially-expressed genes (DEGs) between PTC patients and normal individuals were identified. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of DEGs were performed. Modules in the protein-protein interaction (PPI) network were identified. Significant target genes were selected from the microRNA (miRNA) regulatory network. Furthermore, the integrated network was constructed with the miRNA regulatory and PPI network modules, and key target genes were screened. A total of 668 DEGs were identified. Modules M1, M2 and M3 were identified from the PPI network. From the modules, DEGs of cyclin-dependent kinase inhibitor 1A, S100 calcium binding protein A6 (S100A6), dual specificity phosphatase 5, keratin 19, met proto-oncogene (MET) and lectin galactoside-binding soluble 3 were included in the Malacards database. In the miRNA regulatory and integrated networks, genes of cyclin-dependent kinase inhibitor 1C (CDKN1C), peroxisome proliferator activated receptor gamma, aryl hydrocarbon receptor, basic helix-loop-helix family, member e40 and reticulon 1 were the key target genes. S100A6, MET and CDKN1C may exhibit key roles in the progression and development of PTC, and may be used as specific therapeutic targets in the treatment of PTC. However, further experiments are required to confirm these results. PMID- 26870167 TI - High mobility group box 1 regulates tumor metastasis in cutaneous squamous cell carcinoma via the PI3K/AKT and MAPK signaling pathways. AB - The present study examined the mechanisms of high mobility group box 1 (HMGB1) induced cell migration in human cutaneous squamous cell carcinoma (CSCC) SCC13 cells. Western blotting, a chemotaxis assay and ELISA were performed to analyze HMGB1 level in SCC13 cells and its ability to regulate tumor metastasis. The results demonstrated a significantly higher level of HMGB1 in the SCC13 cell supernatant compared with the human epidermoid carcinoma A431 cell supernatant. Administration of HMGB1 to the SCC13 cells caused cell migration, which occurred in a time- and dose-dependent manner. Moreover, HMGB1 significantly activated the phosphosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways by an increased level of phosphorylation in p85PI3K, AKT, p38 and p42/44 MAPK. Taken together, these data suggest that HMGB1 regulates tumor metastasis in CSCC via the PI3K/AKT and MAPK signaling pathways. PMID- 26870168 TI - MMP-1/2 and TIMP-1/2 expression levels, and the levels of collagenous and elastic fibers correlate with disease progression in a hamster model of tongue cancer. AB - In the present study, the presence of extracellular matrix components, including collagenous and elastic fibers, and the expression of their key regulating enzymes, were investigated in different stages of hamster tongue carcinoma development. Immunohistochemical and computer-assisted morphological analyses were performed to quantify the staining intensity and area (integral optical density) of matrix metalloproteinase (MMP)-1 and -2, tissue inhibitors of metalloproteinase (TIMP)-1 and -2, and the extent of elastic and collagenous fibers in histological sections. MMP-1, MMP-2, TIMP-1 and TIMP-2 expression levels gradually increased with tongue cancer progression, and were associated with disease pathology staging (r=0.705, 0.633, 0.759 and 0.751, respectively). By contrast, elastic fiber levels gradually decreased with cancer progression and were negatively correlated with disease staging (r=-0.881). The levels of collagenous fibers gradually increased with cancer progression and showed a positive correlation (r=0.619). In summary, the study demonstrated that MMP1/2 and TIMP1/2 expression levels, and collagenous and elastic fiber levels were significantly correlated with disease progression in a hamster model of tongue cancer. PMID- 26870169 TI - Expression and prognostic value of SFRP1 and beta-catenin in patients with glioblastoma. AB - The roles of secreted frizzled-related protein-1 (SFRP1) and beta-catenin in human cancer have been widely studied, and it has recently been demonstrated that these proteins are associated with numerous human carcinomas. However, their clinical significance in glioblastoma multiforme (GBM) has not been examined. The current study aimed to analyze the correlation between the expression of SFRP1 and beta-catenin, and clinicopathological characteristics in GBM patients. The expression of SFRP1 and beta-catenin was assessed by immunohistochemistry in 113 samples of GBM and 40 normal brain tissues. Compared with normal brain tissues, GBM tissues exhibited significantly lower expression of SFRP1, and higher expression of beta-catenin (both P<0.05). A Kaplan-Meier analysis revealed that patients with positive SFRP1 expression had a significantly longer overall survival (OS) time relative to those with negative SFRP1 expression (P<0.000), and that patients with positive beta-catenin expression had a shorter OS time than those with negative beta-catenin expression (P<0.000). A multivariate Cox regression analysis indicated that adjuvant treatment, SFRP1 expression and beta catenin expression were independent prognostic factors for OS (P<0.000, P=0.008 and P=0.001, respectively) in patients with GBM. The current data suggest that expression of SFRP1 and beta-catenin may be considered significant prognostic indicators for patients with GBM. PMID- 26870170 TI - Effect of overexpression of HOX genes on its invasive tendency in cerebral glioma. AB - Transcription factors encoded by HOX genes are vital in the determination of cell fate and identity during embryonic development. In certain malignancies, HOX genes also behave as oncogenes. The present study demonstrated suppression of the invasive tendency of glioblastoma multiforme U-118 and U-138 cells by the introduction of the antisense fragments of HOXA6 and B13 genes using electroporation. The invasion index indicated 79 and 72% reductions in the invasive ability of antisense HOXA6 and B13, respectively. No significant differences in the invasive index of the parental and mock cells of each HOX gene were observed (invasive index, 0.75-0.91; P=0.05). A reduction in invasion tendency was also observed following betulinic acid (BA) treatment: The results from the matrigel assay analysis clearly demonstrated a significant inhibition in the invasive behaviour of U-118 and U-138 cell lines from day 15 following BA treatment, with a maximum effect on day 30. The invasion index demonstrated 62 and 65% reductions in invasion ability in the U-118 and U-138 cell lines, respectively. The suppression of HOXC6 and B13 expression by the introduction of the corresponding antisense fragments in addition to BA reduced invasion tendency in U-118 and U-138 cell lines. The mechanism underlying the association between the HOX gene and invasive behavior in glioma cells is yet to be understood. However, the anti-invasive behavior of BA may aid understanding of the mechanism in future studies. PMID- 26870171 TI - Alveolar soft-part sarcoma in the left forearm with cardiac metastasis: A case report and literature review. AB - Alveolar soft-part sarcoma (ASPS) is an uncommon soft-tissue neoplasm, which is commonly found in the deep soft tissues of the extremities, with a propensity for recurrence and metastasis. However, the metastasis of ASPS to the heart is exceedingly rare. The present study reports such a rare case with cardiac metastasis. Using computed tomography, a 37-year-old man was diagnosed with brain, lung and spleen metastases from a previously treated ASPS in the left forearm. Cardiac metastasis was then diagnosed 1 month later. Despite chemotherapy and palliative whole-brain radiotherapy, the patient succumbed to the disease shortly after. This case suggests that the widespread metastases and cardiac involvement of ASPS may result in a poor outcome. PMID- 26870172 TI - Immunosuppressant therapy successfully improved regorafenib-induced severe hepatic injury in a patient with metastatic gastrointestinal stromal tumor: A case report. AB - A 75-year-old man diagnosed with ileal gastrointestinal tumor with peritoneal dissemination was subjected to salvage treatment with regorafenib at 120 mg/day. Following the initiation of the treatment, liver dysfunction appeared on day 28, and continued to worsen despite termination of the treatment. Since no increase in the levels of serum immunoglobulins of the patient was observed, and negative results were obtained for the analysis of viral markers and autoantibodies, a diagnosis of regorafenib-induced hepatitis was suggested. In consequence, the patient received steroid pulse therapy and continuous administration of prednisolone, without sufficient improvement. Liver biopsy revealed interface hepatitis with prominent plasma cell infiltration, suggesting regorafenib-induced autoimmune hepatitis. The patient was then administered azathioprine and prednisolone, which improved the hepatic injury. The present case represents the first report of successful treatment of regorafenib-induced severe hepatic injury by the use of an immunosuppressant. PMID- 26870173 TI - Primary alveolar soft part sarcoma of the right femur and primary lymphoma of the left femur: A case report and literature review. AB - Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor, particularly in bone, which usually affects young patients. Primary lymphoma of bone (PLB) is a rare form of non-Hodgkins lymphoma that occurs primarily in bone. In the present report, the case of a 42-year-old woman affected by ASPS and PLB in the left and right femur, respectively, is presented. The radiological features of digital radiography, computed tomography and magnetic resonance imaging examination are discussed, and compared with previous findings reported in the literature. To the best of our knowledge, the present study is the first case of ASPS and PLB occurring concomitantly in a patient. PMID- 26870174 TI - Malignant renal epithelioid angiomyolipoma: A case report and review of the literature. AB - Malignant renal epithelioid angiomyolipoma (EAML) is rare, and currently there is no malignant criteria for its pathological diagnosis. In the present study, the case of a patient who suffered malignant renal EAML and underwent nephrectomy is reported. The histological patterns of the tumor were composed of sheets or nests of large polygonal epithelioid cells and thick-walled blood vessels, with clear mitoses. Immunohistochemistry demonstrated that the epithelioid and smooth muscle cells characteristically expressed human melanoma black-45, epithelial membrane antigen and actin. Pathological evaluation revealed malignant EAML with regional lymph node metastases. Magnetic resonance imaging and X-ray examination identified multiple liver and lung nodules at 16 months post-surgery. Since the patient did not respond to the initial treatment with doxorubicin and cisplatin, sorafenib was subsequently administered. However, the treatment was not effective, and the patient succumbed to multiple metastases six months later. PMID- 26870175 TI - Phosphorylation of BMK1 induces prostatic carcinoma cell proliferation by promoting entry into the S phase of the cell cycle. AB - Big mitogen-activated protein kinase 1 (BMK1) is activated by mitogens and oncogenic signals, and is strongly implicated in tumorigenesis. In the present study, it was demonstrated that the activation of BMK1, but not extracellular signal-regulated kinase (ERK)1/2, can induce proliferation in prostate cancer cells. It was found that the proliferation of epidermal growth factor (EGF) treated cells was accelerated by 40% compared with non-treated cells using a CCK8 assay. In addition, cell cycle analysis using flow cytometry showed that the proportion of cells in the S phase increased significantly in the BMK1-activated PC-3 cells, suggesting that the activation of BMK1 promotes entry into the S phase of the cell cycle in prostate cancer cells. Furthermore, western blot analysis indicated that EGF-mediated activation of BMK1, but not ERK1/2, participates in the proliferation and cell cycle regulation in prostate cancer cells. Furthermore, the effects of cell cycle regulation by the activation of BMK1 were associated with the increased expression levels of cyclin A and cyclin E, whereas the expression of cyclin B and cyclin D1 was unchanged in this process. Therefore, the present study demonstrated that the activation of BMK1 can induce proliferation by promoting entry into the S phase through the upregulation of cyclin A and cyclin E expression levels in prostate cancer cells. PMID- 26870176 TI - Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma. AB - Multiple osteochondroma (MO), also known as multiple hereditary exostoses, is an autosomal dominant skeletal disorder with characteristic multiple cartilage capped tumours (osteochondromas or exostoses) growing outward from the metaphyseal region of the long tubular bones. Mutations in exostosin glycosyltransferase 1 (EXT1) or EXT2 are the most commonly associated mutations with MO and are responsible for 70-95% of cases. In the present study, a genetic analysis was performed on a large family with MO using polymerase chain reaction and direct DNA sequencing of the entire coding regions of EXT1 and EXT2. Sanger sequencing identified a novel heterozygous frameshift mutation, c.119_120delCT (p.Thr40ArgfsX15), in exon 2 of the EXT2 gene in the proband and all other affected individuals, while this deleterious mutation was not detected in the healthy family members and normal controls. The c.119_120delCT mutation is located in the transmembrane region of the EXT2 protein and results in a truncated EXT2 protein lacking 665 amino acids at the C-terminus, which includes the critical exostosin and glycosyltransferase family 64 domains. Thus, the present study identified a novel causative frameshift mutation in EXT2 from a large MO family. This study is useful for extending the known mutational spectrum of EXT2, for understanding the genetic basis of MO in the patients studied, and for further application of mutation screening in the genetic counseling and subsequent prenatal diagnosis of this family. PMID- 26870177 TI - Correlation between the expression of hTERT gene and the clinicopathological characteristics of hepatocellular carcinoma. AB - The aim of the present study was to detect the expression levels of the human telomerase reverse transcriptase (hTERT) gene in hepatocellular carcinoma (HCC), and investigate its significance in the incidence and development of the cancer. HCC tissues and corresponding para-carcinoma liver tissues were surgically collected from 78 patients with HCC who presented to Shandong Provincial Hospital (Jinan, Shandong, China). hTERT expression at the protein and mRNA levels were detected by immunohistochemistry (streptavidin peroxidase method) and reverse transcription polymerase chain reaction, respectively, in the HCC tissues and corresponding para-carcinoma liver tissues of 78 HCC patients and in 12 samples of normal liver tissue. The data were analyzed using SPSS 17.0 statistical software, and employing chi2 tests and t-tests. hTERT protein was mainly expressed in the HCC cell cytoplasm, but was occasionally observed in the cell nucleus. The positive rates of hTERT protein and mRNA expression in the HCC patients were 84.62% (66/78) and 78.21% (61/78), respectively, which was significantly higher compared with the rates of 10.26% (8/78) and 8.97% (7/78) in the paired para-carcinoma liver tissues (P<0.01). hTERT protein and mRNA were not expressed in the normal liver tissues (0/12). chi2 test and t-test analysis revealed that hTERT gene expression was correlated with tumor grade, the presence/absence of a portal vein tumor thrombus, hepatitis B surface antigen positivity and a high alpha-fetoprotein level (P<0.05) rather than patient age, gender or tumor size. Expression of the hTERT gene may play a pivotal role in the incidence and development of HCC. The hTERT gene potentially serves as an important molecular and biological index for diagnosing and predicating the biological behavior of HCC. PMID- 26870178 TI - Expression of pigment epithelium-derived factor is associated with a good prognosis and is correlated with epithelial-mesenchymal transition-related genes in infiltrating ductal breast carcinoma. AB - Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E cadherin, vimentin, Snail and nuclear factor-kappaB (NF-kappaB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-kappaB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-kappaB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF- and E cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF kappaB-positive tumors. Vimentin, E-cadherin and NF-kappaB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation. PMID- 26870179 TI - Gene expression profiling analysis of MENX-associated rat pituitary adenomas contributes to understand molecular mechanisms of human pituitary adenomas. AB - The present study aimed to screen potential genes associated with pituitary adenomas to obtain further understanding with regard to the pathogenesis of pituitary adenomas. The microarray GSE23207 dataset, containing 16 pituitary adenoma samples from multiple endocrine neoplasia syndrome-associated rats and 5 normal pituitary tissue samples, was downloaded from Gene Expression Omnibus. The Linear Models for Microarray Data package was used to identify the differentially expressed genes (DEGs) with the cut-off criteria of a |log2fold change (FC)|>1 and adjusted P-values of <0.05. The potential functions of the DEGs were predicted by functional and pathway enrichment analysis with the Database for Annotation, Visualization and Integrated Discovery. Furthermore, the interaction associations of the up- and downregulated DEGs obtained from the Search Tool for the Retrieval of Interacting Genes database were respectively revealed by the protein-protein interaction networks visualized with Cytoscape. A total of 391 upregulated and 238 downregulated DEGs in were screened in the pituitary adenoma samples. The upregulated DEGs with a higher degree in the protein-protein interaction network (e.g., CCNA2, CCNB1 and CDC20) were significantly involved in cell cycle and cell division. Notably, PTTG1 was enriched in every functional term. These DEGs interacted with each other. The downregulated DEGs (e.g., GABRA1, GABRA4 and GABRB1) also interacted with each other, and were relevant to neuroactive ligand-receptor interaction; the DEG POU1F1, interacting with POMC, was correlated with the development of the pituitary gland, adenohypophysis and endocrine system. Certain DEGs, including CCNB1, CCNA2, CDC20, GABRA1, GABRA4, GABRB1, POU1F1 and POMC, and particularly PTTG1, were shown to be closely involved in the pathogenesis of pituitary adenomas. PMID- 26870180 TI - MicroRNA-183-5p promotes the proliferation, invasion and metastasis of human pancreatic adenocarcinoma cells. AB - The aim of the current study was to investigate the potential role of microRNA 183-5p (miR-183-5p) in the proliferation, invasion and metastasis of pancreatic cancer, and to identify promising target genes of oncogenic miR-183-5p. Western blotting and quantitative polymerase chain reaction (qPCR) were used to investigate whether these oncogenic microRNAs may be useful as biomarkers in pancreatic carcinoma (PaCa). Potential target genes were verified using miRDB, PicTar and TargetSCAN, and qPCR was used to detect the expression of miR-183 and suppressor of cytokine signaling 6 (SOCS-6; a potential target of miR-183) in PANC-1 PaCa cells and in the HPDE6-C7 pancreatic ductal cell line for comparison. The function of miR-183 in cell proliferation, wound healing, invasion and migration was also investigated using a miR-183 inhibitor. Western blot analysis was used to confirm SOCS-6 as a tumor suppressor and qPCR was used to detect and confirm that this potential target gene is directly regulated by miR-183. The results indicated that the expression of miR-183 in PANC-1 cells was upregulated compared with that in HPDE6-C7 cells, whilst the expression of SOCS-6 was downregulated. SOCS-6 expression was also significantly lower in PaCa tissues compared with that in matched normal pancreatic tissues from PaCa patients. Furthermore, expression of miR-183 was inversely correlated with that of SOCS-6. miR-183 knockdown decreased cell growth and motility in pancreatic cancer cells and significantly increased the expression of SOCS-6. These data suggest that oncogenic miR-183 may be useful as a pancreatic cancer biomarker. In addition, inhibition of miR-183 expression may be beneficial as PaCa treatment. SOCS-6 is a potential target gene of miR-183. PMID- 26870181 TI - De-escalation of radiation dose for human papillomavirus-positive oropharyngeal head and neck squamous cell carcinoma: A case report and preclinical and clinical literature review. AB - Traditionally, head and neck squamous cell carcinoma (HNSCC) has been considered to be a relatively homogeneous disease. However, recent data have demonstrated that human papillomavirus (HPV)-positive and HPV-negative disease are two different clinical entities associated with different outcomes. Preclinical and clinical studies have reported a divergence in treatment strategies as well as prognostic outcomes for HNSCCs that are HPV-positive versus HPV-negative. The present study describes the case of a 52-year-old man who presented with stage IVB cT2N3M0 right tonsillar HPV-positive squamous cell carcinoma. Induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF), followed by chemoradiation therapy with carboplatin and 70 Gray (Gy) radiation in daily fractions was recommended. The patient completed the TPF and carboplatin treatment; however, he was unable to tolerate the radiation course, receiving a final dose of 46 Gy. A 60-day follow-up right neck salvage dissection was subsequently performed. Despite having received a partial radiation treatment of 46 Gy, the patient had no pathological evidence of disease at 60 days post radiation treatment. Repeat positron emission tomography-computed tomography at 32 months after the right neck dissection revealed no evidence of disease. The present study also discusses the current preclinical in vitro and in vivo targets for HPV-positive HNSCC and the obstacles presented in advancing clinical treatment modalities. Previous preclinical models investigating radiation sensitivity have yielded mixed results. Thus, it is important to understand and establish representative preclinical models for studying HPV and HNSCC to improve clinical research and therapeutic development. This review may guide future understanding of the role of HPV in HNSCC. PMID- 26870182 TI - Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells. AB - Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a naturally occurring plant polyphenol, isolated from water caltrop, which has been reported to exert anticancer effects. The present study investigated the antiproliferative effects of GA on the HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cell lines using MTT and colony formation assays. In particular, the underlying mechanism of GA-induced apoptosis in SMMC-7721 cells was studied in vitro by flow cytometry and western blotting. The results of the present study indicated that GA was capable of inhibiting the proliferation of HepG2 and SMMC-7721 cells in a time- and dose-dependent manner, as well as inducing the apoptosis of SMMC-7721 cells. GA induced caspase-3, caspase-9 and reactive oxygen species activity, elevated the expression of apoptosis regulator Bcl-2-like protein 4 and reduced the mitochondrial membrane potential in SMMC-7721 cells. When compared with HL-7702 normal human hepatocytes, GA demonstrated selective toxicity for HCC cells. In conclusion, GA is able to induce apoptosis in SMMC-7721 cells in vitro via mitochondrial-mediated pathways, and may possess the potential to be a novel therapeutic compound for use in the treatment of HCC. PMID- 26870183 TI - Downregulation of survivin expression exerts antitumoral effects on mouse breast cancer cells in vitro and in vivo. AB - Metastasis constantly occurs in the majority of cases of primary breast cancer at late stage or following surgical treatment. Survivin, a member of the inhibitor of apoptosis protein family, has long been recognized as a promising anticancer target, but its antitumor effects remain largely unexplored. In order to elucidate the role of survivin in breast cancer metastasis, short interfering RNA (siRNA) was used in the present study to specifically downregulate survivin expression in the murine breast cancer cell line 4T1. The results demonstrated that blocking the expression of survivin by siRNA inhibited the proliferation, migration and invasion abilities of murine breast cancer cells in vitro. Vascular endothelial growth factor (VEGF)-C is a lymphatic endothelial cell-stimulating factor that may lead to the formation of lymphatic vessels in lymph nodes. In the present study, the inhibition of survivin by siRNA was able to reduce the overexpression of VEGF-C in 4T1 cells. Furthermore, intratumoral injections of the survivin-siRNA significantly inhibited the growth of orthotopically transplanted 4T1 tumors in vivo. In addition, the number of pulmonary metastases and the microlymphatic vessel density were significantly reduced in vivo, following transfection with survivin-siRNA. The results of the present study suggested that the Akt/hypoxia-inducible factor-1alpha signaling pathway participates in the survivin-mediated downregulation of VEGF-C expression observed in breast cancer cells treated with survivin-siRNA. Therefore, the use of siRNA specifically targeting survivin may be a potential anticancer method in the future. PMID- 26870184 TI - Knockdown of protein phosphatase 5 inhibits ovarian cancer growth in vitro. AB - Ovarian cancer is the most common cause of gynecological cancer-related mortality. Serine/threonine protein phosphatase 5 (PP5, PPP5C) has been recognized to be involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, including cell growth, differentiation, proliferation, motility and apoptosis. In this study, to evaluate the functional role of PP5 in ovarian cancer cells, lentivirus-mediated RNA interference (RNAi) was applied to silence PPP5C in the human ovarian cancer cell line CAOV-3. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. Cell colony forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. The results demonstrated that lentivirus-mediated RNAi specifically suppressed the expression of PPP5C at the mRNA and protein levels in CAOV-3 cells. Further investigations revealed that PP5 knockdown significantly inhibited the proliferation and colony formation of CAOV-3 cells. Moreover, the cell cycle of CAOV-3 cells was arrested at the G0/G1 phase following PP5 knockdown. This study highlights the crucial role of PP5 in promoting ovarian cancer cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of PP5 RNAi therapy for the treatment of ovarian cancer. PMID- 26870185 TI - Epidermal growth factor receptor expression and gene copy number analysis in gastric carcinoma samples from Chinese patients. AB - Epidermal growth factor receptor (EGFR) expression and gene copy number have been observed to be associated with a positive clinical response to EGFR inhibitors. The present study aimed to evaluate EGFR expression and gene copy number in samples of gastric carcinoma (GC) from Chinese patients. EGFR expression and gene copy number were detected using immunohistochemistry and fluorescence in situ hybridization, in tissue array slides containing 150 individual samples of GC tissue. The association between EGFR status, clinicopathological features and overall patient survival was analyzed. Out of the 150 cases of GC evaluated, 63 (42.00%) demonstrated weak EGFR expression and 20 (13.33%) demonstrated EGFR overexpression. EGFR expression was observed to be associated with tumor location (P<0.05). Out of 104 cases of GC, which produced a clear FISH signal, 6 (5.77%) exhibited EGFR gene amplification and 5 (4.80%) exhibited balanced polysomy. Patients exhibiting GC, who demonstrated weak EGFR expression, EGFR overexpression or increased EGFR gene copy number, possessed an unfavorable prognosis. Multivariate analysis revealed that EGFR expression, tumor/node/metastasis stage and tumor location were potential independent unfavorable prognostic factors for GC patients. In conclusion, EGFR overexpression, gene amplification and polysomy were observed in GC patients and were associated with an unfavorable prognosis. Evaluation of EGFR status may therefore facilitate the identification of a subset of GC patients sensitive to treatment with EGFR-targeted therapies. PMID- 26870186 TI - Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. AB - The present study investigated the anti-tumor activity of N-(4 tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox amide (BCTC), a potent and specific inhibitor of transient receptor potential cation channel subfamily M member 8 (TRPM8) in prostate cancer (PCa) DU145 cells. TRPM8 expression in DU145 and normal prostate PNT1A cells was detected by reverse transcription polymerase chain reaction and western blot analysis. The effect of BCTC on DU145 cells was analyzed by flow cytometry analysis, and MTT, scratch motility and Transwell invasion assays. The molecular mechanism through which BCTC acts was investigated by western blot analysis. TRPM8 expression was increased in DU145 cells compared with PNT1A cells at the mRNA and protein levels. The present study provided evidence that inhibition of TRPM8 by BCTC reduced the viability of DU145 cells, but not PNT1A cells. In addition, BCTC inhibited cell cycle progression, migration and invasion in DU145 cells. Cell cycle-associated proteins, including phosphorylated protein kinase B, cyclin D1, cyclin dependent kinase (CDK) 2 and CDK6 were downregulated by BCTC, while phosphorylated glycogen synthase kinase 3beta was upregulated. However, investigations in the present study revealed that BCTC failed to trigger apoptosis in DU145 cells. In addition, in BCTC-treated DU145 cells, phosphorylated extracellular signal-regulated kinase 1/2 was downregulated substantially while phosphorylated p38 (p-p38) and phosphorylated c-Jun N terminal kinases (p-JNK) were upregulated. The anti-proliferative activity of BCTC on DU145 cells was attenuated by p38 and JNK-specific inhibitors, suggesting that MAPK pathways are involved. Overall, the TRPM8 specific antagonist BCTC demonstrated excellent anti-tumor activity in PCa DU145 cells, and therefore has the potential to become a targeted therapeutic strategy against PCa. PMID- 26870187 TI - Large cell neuroendocrine cervical tumor treated by radical surgery and adjuvant chemotherapy: A case report and literature review. AB - Neuroendocrine carcinomas of the uterine cervix are rare, but extremely aggressive, gynecological malignancies that are associated with an overall poor prognosis. The present study reports the case of a 41-year-old patient diagnosed with large cell neuroendocrine cervical tumor. A radical total hysterectomy with bilateral adnexectomy, pelvic and lymph node dissection was performed. The post operative course was uneventful, and the patient was discharged on post-operative day 8. PMID- 26870188 TI - Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer. AB - Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P=0.023]. In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed. PMID- 26870189 TI - Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition. AB - Inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as a novel therapeutic strategy for the treatment of oral squamous cell carcinoma (OSCC). The EGFR-directed inhibitor cetuximab is currently the only approved targeted therapy for the treatment of OSCC. EGFR status may affect the patient response to cetuximab treatment. In the present study, via analysis of the immunomarker for EGFR, it was revealed that 58.3% of the total cases investigated stained positively for EGFR expression, and furthermore, that invasiveness was inversely correlated with EGFR expression. Expression levels of EGFR were quantified, and the correlation between EGFR expression and cetuximab sensitivity was investigated using three varying grades of invasive human OSCC line. EGFR expression in high-grade invasive cells was significantly downregulated compared with that of low-grade invasive cells. There was no significant antiproliferative effect in the high-grade invasive cells treated with various concentrations of cetuximab. The EMT-associated genes, N-cadherin, vimentin and Snail, were upregulated in the high-grade invasive cells. The low-grade invasive cells exhibited characteristics of typical epithelial cells, including the expression of E-cadherin and absence of the expression of N-cadherin, vimentin and Snail. Transforming growth factor-beta induced low-grade invasive cells to undergo an epithelial-mesenchymal transition (EMT)-associated gene switch, which resulted in low levels of EGFR expression. The results of the present study suggested that loss of EGFR expression in OSCC was associated with EMT, and may have functional implications with regard to tumor invasiveness and the resistance to cetuximab treatment. PMID- 26870190 TI - Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife(r) system: A preliminary report. AB - The CyberKnife(r) is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment. PMID- 26870191 TI - Anaplastic lymphoma kinase protein expression predicts micrometastases and prognosis for patients with hepatocellular carcinoma. AB - The present study aimed to investigate anaplastic lymphoma kinase (ALK) status in hepatocellular carcinoma (HCC) and to evaluate whether abnormalities in expression were associated with patient prognosis. ALK status was investigated using immunohistochemistry (IHC), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) assays in 342 HCC patients. In addition, rapid amplification of complementary DNA ends coupled PCR sequencing was performed, in order to confirm the presence of ALK abnormalities in patients exhibiting ALK messenger RNA (mRNA) overexpression. The correlation between ALK expression and the clinicopathological features and prognosis of the HCC patients was statistically analyzed. The results of the present study revealed overexpression of ALK protein and mRNA; furthermore, ALK gene copy number gains were observed via IHC (44.7%; 153/342), RT-qPCR (47.4%; 162/342) and FISH (32.7%; 112/342) analyses, although ALK rearrangement or mutation was not demonstrated in the results of any of these assays. ALK protein expression levels were significantly associated with hepatitis C virus (HCV) status (P<0.001) and the presence of micrometastases (P=0.011). Within the entire patient cohort, ALK expression was associated with poor progression-free survival (PFS; P=0.041). Subsequent analysis in patient subgroups that demonstrated hepatitis B surface antigen positivity, HCV negativity, stage III-IV disease, recurrence and micrometastasis positivity revealed that overall survival (OS) and PFS were significantly reduced in those patients exhibiting ALK expression compared with those patients who were negative for ALK expression. Multivariate analysis revealed that ALK expression was an independent risk factor for OS (P=0.042) and PFS (P=0.033), particularly for patients with stage III-IV tumors. Thus, ALK may serve as a novel indicator for the metastatic behavior and prognosis of HCC. PMID- 26870193 TI - Early tumor cavitation with regorafenib in metastatic colorectal cancer: A case report. AB - Tumoral cavity formation is a characteristic phenomenon reported in anti angiogenic therapy in lung lesions. A 57-year-old male with multiple pulmonary metastases from colorectal cancer treated with an oral tyrosine kinase inhibitor, regorafenib, exhibited a characteristic cavity formation after the first two cycles. The decrease in the size of tumors was calculated as 38%, and there were associated decreases in the serum concentrations of the tumor markers carcinoembryonic antigen and CA19-9. After eight cycles of treatment, the cavity gradually disappeared through filling-in. This unique morphological response is not only reported in lung cancer but also in liver metastasis in colorectal cancer. However, the association between morphological changes including cavity formation and clinical benefit remains controversial. Pulmonary hemorrhage and pneumothorax are well-known consequences of cavitation, as reported with the other anti-angiogenic inhibitors. Early tumor cavitation in lung metastasis may demonstrate the predictive potential of regorafenib in colorectal cancer, although it is necessary to be mindful of toxicity. PMID- 26870192 TI - Clinicopathological and prognostic significance of metastasis-associated protein 1 expression and its correlation with angiogenesis in lung invasive adenocarcinomas, based on the 2011 IASLC/ATS/ERS classification. AB - Based on previous findings regarding the angiogenic activities and prognostic roles of metastasis-associated protein 1 (MTA1) in early-stage non-small cell lung cancer, the clinicopathological and prognostic significance of MTA1 protein expression, and its correlation with angiogenesis in lung invasive adenocarcinoma, were further assessed in the present study, according to the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. High protein expression levels of MTA1 were commonly observed in patients with lung invasive adenocarcinoma, and were significantly correlated with tumor size (P=0.030), lymph node metastasis (P=0.021) and microvessel density (P=0.015). Survival analysis demonstrated that patients with high protein expression levels of MTA1 exhibited significantly shorter five-year disease-free and overall survival than those patients whose protein expression levels of MTA1 were low (24.5% vs. 48.7%, P=0.001, and 34.7% vs. 59.2%, P=0.005, respectively). In addition, Cox regression multivariate analysis demonstrated that high protein expression levels of MTA1 significantly correlated with unfavorable five-year disease-free survival (P=0.024). These findings indicate that MTA1 protein expression may possess clinical potential as an indicator of progressive phenotype. Therefore, MTA1 is a promising prognostic predictor to identify subgroups of patients with high risk of relapse, and a potentially novel therapeutic target for antiangiogenesis in patients with lung invasive adenocarcinoma. PMID- 26870194 TI - Expression and clinical significance of Oct-4 and E-cad in non-small-cell lung cancer. AB - Non-small-lung cancer (NSCLC) is a common malignant tumor and is a leading cause of cancer mortality. Tumor stem cells are associated with tumor pathogenesis and development as well as invastion and metastasis. In the present study, the expression and correlation of tumor stem cell markers, octamer-binding transcription factor 4 (Oct-4) and E-cadherin (E-cad) in NSCLC and normal lung tissue were investigated. Additionally, the molecular mechanisms of invasion and metastasis of NSCLC were assessed. The expression of Oct-4 and E-cad was examined in 65 pathologically diagnosed cases of NSCLC using immunohistochemistry. The correlation between Oct-4 and E-cad, as well as the association with pathological grade and clinical staging were also analyzed. Fifteen cases of normal lung tissues served as the control. The positive expression of Oct-4 and abnormal expression of E-cad was higher in the NSCLC tissue compared to the normal lung tissue, and increased as NSCLC malignancy increased. The differences in each grade each stage were statistically significant (P<0.05). A correlation was identified between the abnormal expression of Oct-4 and E-cad (P<0.05, coefficient of contingency C=0.439). In conclusion, the expression of Oct-4 promoted the epithelial-mesenchymal transition in lung cancer. PMID- 26870195 TI - Magnifying chromoendoscopic and endocytoscopic findings of juvenile polyps in the colon and rectum. AB - A precise endoscopic diagnosis is necessary for endoscopic therapy for neoplastic and non-neoplastic lesions, including juvenile polyps (JPs). Therefore, the present study aimed to clarify the characteristic endoscopic findings of JPs. A total of 154 JPs were evaluated by magnifying chromoendoscopy, 20 of which were also assessed by endocytoscopy using an ultra-high magnification endoscope. Endoscopic images were evaluated in terms of gross appearance, color, pit pattern, surface inflammatory changes and vascularity of polyps. Endocytoscopic images were evaluated with regard to the morphology of glandular cavities, nuclei of glandular cells and interstitial features. Reddish surfaces (98.1%), surface erosion (92.2%), open pits (90.3%) and low pit density (90.3%) were observed in the majority of JPs by chromoendoscopy. In addition, dilated ductal openings surrounded by normal glandular cells (100%), greater distances between gland basal layers (100%) and interstitial infiltration by inflammatory cells (100%) were observed in all JPs examined by endocytoscopy. These findings indicate that there is a tetralogy of magnifying chromoendoscopic findings characteristic of JPs: Reddish surfaces, surface erosion, open pits and low pit density. There is also a triad of endocytoscopic findings characteristic of JPs, namely dilated ductal openings surrounded by normal glandular cells, greater distances between gland basal layers, and interstitial infiltration by inflammatory cells. The aforementioned magnifying chromoendoscopic and endocytoscopic characteristics of JPs may be useful factors for diagnosing JPs. PMID- 26870196 TI - Disappearance of giant cells and presence of newly formed bone in the pulmonary metastasis of a sacral giant-cell tumor following denosumab treatment: A case report. AB - A giant-cell tumor of the bone (GCTB) is a benign but locally aggressive bone tumor. Recently, the receptor activator of nuclear factor kappaB (RANK) ligand inhibitor, denosumab, has demonstrated activity against giant-cell tumors. The current study reports a case of a sacral GCTB with lung metastasis. A 19-year-old male patient presented with right buttock pain and right lower leg pain, and a sacral GCTB was diagnosed based on the histological analysis of a biopsy specimen. The patient was successfully treated with neoadjuvant denosumab therapy, which allowed curettage. In addition, the pulmonary nodule reduced in size following denosumab administration, and surgical resection was performed. Since the operation, the patient has been managed with the continued use of denosumab with no sign of recurrence. Microscopic findings from the surgical specimen following denosumab treatment revealed that the giant cells had disappeared and woven bone had formed. The specimen from the pulmonary nodule exhibited similar findings to the surgical specimen. It was reported that denosumab treatment was able to reduce the number of giant cells and RANK positive stromal cells, and cause the formation of new bone in the primary lesion. The present study reports the first case to demonstrate the efficiency of denosumab in treating pulmonary metastasis of GCTB. PMID- 26870197 TI - Treatment of bone defect with calcium phosphate cement subsequent to tumor curettage in pediatric patients. AB - The aim of the present study was to investigate the mid- to long-term clinical performance of calcium phosphate cement (CPC) in the treatment of benign bone tumors in pediatric patients with a follow-up of at least 2-years. The cases of 33 patients with benign bone tumors treated by curettage and subsequent implantation of CPC were retrospectively reviewed. The patients consisted of 13 males and 20 females, with a median age of 13 years and median follow-up time of 79 months. All patients were alive at the time of review. No toxicity was detected in routine blood tests. Radiography was used to confirm that CPC was well adapted to the surrounding host bone, although the resorbability of CPC was not obtained for all patients at the final follow-up. Local tumor recurrence occurred in 4 patients. None of the patients reported post-operative fractures. In total, 6 patients required a second surgical procedure, as follows: 4 patients in whom local tumor recurrence occurred; 1 patient with post-operative superficial wound infection, who underwent wound debridement; and 1 patient that required the removal of CPC due to deep infection at the proximal humerus. All patients had regained full physical function without any pain at the final follow up. The present study recommends that the properties of CPC should be taken into consideration and applied to the reconstruction of bone defects subsequent to curettage of bone tumors. PMID- 26870198 TI - Askin's tumor: 11 cases and a review of the literature. AB - Askin's tumor is a peripheral primitive neruoectodermal tumor within the thoracopulmonary region, which primarily occurs in children and young adults. In addition, Askin's tumor is commonly misdiagnosed, as it is rare and easily mistaken for other small round-cell tumors. The present study aimed to investigate the clinical characteristics, prognostic factors and treatment outcomes of patients diagnosed with Askin's tumor. Computed tomography (CT) scans, histopathology and immunohistochemical analysis were used for diagnosis. Patients were treated with combined (surgery-chemotherapy-radiotherapy) or mono therapy (chemotherapy or radiotherapy) methods. A total of 11 consecutive patients with Askin's tumor (aged 8-22 years) were treated at the First Affiliated Hospital of Zhengzhou University between April 2010 and June 2013; nine patients underwent combined therapy and two patients were treated using mono therapy. Chest lumps, swelling and pain were the most common presenting symptoms. Patients were followed up for <=24 months post surgery and the results revealed that the median survival time of the combined and mono-therapy treatment groups were 15 and 7 months, respectively. Primary tumor size, metastasis, lactate dehydrogenase indicators and tumor stages were found to be important prognostic factors affecting patient outcome. In conclusion, the results of the present study demonstrated that the combination of surgery, chemotherapy and radiotherapy resulted in the optimal outcome for Askin's tumor patients. PMID- 26870199 TI - Neuroendocrine carcinoma of the ureter: A case report and literature review. AB - Primary neuroendocrine carcinoma (NEC) of the ureter is a rare entity, with few cases reported in the literature. These tumors are usually locally aggressive and are associated with a poor prognosis due to the thin walls of the ureter. This is the case report of a 69-year-old male patient who presented with left flank pain and gross hematuria. Following diagnosis of ureteral carcinoma, nephroureterectomy was performed. Postoperatively, the patient refused chemotherapy and radiotherapy, and succumbed to extensive metastases after 12 months of follow-up. The aim of the present study was to provide a literature review of NEC and its clinical and pathological characteristics, diagnostic methods and latest modifications in therapy. PMID- 26870200 TI - Clinical and computed tomography imaging features of renal medullary carcinoma: A report of six cases. AB - Patients with renal medullary carcinoma (RMC) have a poor prognosis, usually due to late diagnosis. Computed tomography (CT) analysis may aid the differentiation between RMC and other types of renal cell carcinoma, in order to establish an accurate early diagnosis. There is a limited number of reports in the literature focusing on clinical and multi-slice CT (MSCT) imaging findings of RMC. Consequently, the present study aimed to characterize the clinical and MSCT imaging features of RMC. For this purpose, the MSCT imaging findings of 6 patients with RMC were retrospectively studied. The patients were subjected to MSCT in order to investigate the characteristics of the tumors, including location, size, density, calcification, cystic or solid appearance, capsule sign, enhancement pattern and presence of retroperitoneal lymph node metastasis. The tumors in the current study presented a mean diameter of 7.48+/-3.25 cm, and were observed to be solitary and heterogeneous with necrotic components. The majority of the tumors did not contain calcifications (5/6); displayed an ill-defined margin (4/6); were centered in the medulla; extended into the renal pelvis or peripelvic tissues (6/6); and did not exhibit a fibrous capsule. Localized caliectasis was observed in 3 of the 6 cases. The attenuation of the solid region of the RMC on unenhanced CT was equal to that of the renal cortex or medulla (42.3+/-2.7 vs. 40.7+/-3.6 and 41.2+/-3.9 Hounsfield units, respectively; P>0.05) while, on enhanced CT, the enhancement of the tumor was lower than that of the normal renal cortex and medulla during all phases (cortical phase, 52.6+/-4.8 vs. l99.5+/-9.7 and 72.7+/-6.4; medullary phase, 58.6+/-5.7 vs. 184.6+/-10.8 and 93.5+/-7.8; delayed phase, 56.8+/-6.1 vs. 175.7+/-8.5 and 96.5+/-7.9, respectively; P<0.05). In conclusion, RMC tends to be an infiltrative, ill defined heterogeneous mass with intratumoral necrosis, which arises from the renal medulla, and displays lower enhancement than the renal cortex and medulla during all phases on enhanced CT. Despite its rarity in adults, RMC should be included in a differential diagnosis when CT imaging reveals these features. PMID- 26870202 TI - Double primary hepatic cancer (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) in a single patient: A case report. AB - Double primary hepatic cancer, consisting of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) located separately within a single liver simultaneously, is extremely rare. The present study reports a case of double hepatic nodules, in which HCC and ICC occurred simultaneously in the right hepatic lobe. The 47-year-old male patient, who was a carrier of hepatitis B virus, was admitted to our hospital for physical examination, which revealed two liver masses. The results of initial laboratory tests, including liver function tests, were within normal limits, with the exception of mildly elevated aspartate aminotransferase and alanine aminotransferase, and decreased albumin levels. alpha-fetoprotein was in the normal range, while carbohydrate antigen 19-9 was marginally elevated. Abdominal ultrasonography and enhanced computed tomography revealed two tumors located in segments (S) VI and VII of the liver, respectively, with malignant behavior. Examination of the two masses following resection of S VI and VII confirmed a diagnosis of combined HCC and ICC. After 8 months of follow-up, no signs of recurrence have been observed with chemical therapy. PMID- 26870201 TI - Differential effect of psoralidin in enhancing apoptosis of colon cancer cells via nuclear factor-kappaB and B-cell lymphoma-2/B-cell lymphoma-2-associated X protein signaling pathways. AB - Worldwide, colon cancer is the third most common cancer in terms of incidence, following lung and breast cancer. Resistance to psoralidin frequently occurs following its use as an anticancer treatment. However, the mechanisms underlying the effects of psoralidin on colon cancer, remain to be elucidated. Hence, the present study investigated the anticancer effects and potential mechanism of action of psoralidin on SW480 human colon cancer cells. In the present study, an MTT assay was performed to measure the viability of SW480 cells. Additionally, an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit, DAPI staining assay and caspase-3 colorimetric assay kits were used to analyze the cellular apoptosis of SW480 cells. The nuclear factor-kappaB (NF-kappaB) p65 activity and B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) protein expression of SW480 cells was detected using NF-kappaB colorimetric assay kits and western blot analysis, respectively. Bcl-2 inhibitor ABT-737 was added to SW480 cells and the subsequent effects and mechanism of action of psoralidin on SW480 colon cancer cells was studied. In the present study, psoralidin reduced SW480 cell viability and enhanced the cellular apoptosis of SW480 cells in a dose dependent manner. Caspase-3 activity of SW480 cells was increased following treatment with psoralidin. Additionally, psoralidin was able to reduce the NF kappaB p65 activity of SW480 cells. Furthermore, psoralidin was able to reduce Bcl-2 protein expression and increase Bax protein expression in SW480 cells. Notably, Bcl-2 inhibitor was observed to enhance the effects of psoralidin on SW480 cells. The results of the present study suggest that psoralidin may be a candidate drug for the treatment of colon cancer by inhibition of the NF-kappaB and Bcl-2/Bax signaling pathways. PMID- 26870203 TI - GADD45A expression is correlated with patient prognosis in esophageal cancer. AB - The prognosis of patients with esophageal cancer remains poor, and the tumor-node metastasis classification system is not sufficient for predicting patient prognoses. Therefore, the identification of novel predictive markers for esophageal cancer is required. The present study investigated the clinicopathological significance of growth arrest and DNA damage-inducible 45alpha (GADD45A) and p53 in resectable esophageal squamous cell carcinoma (ESCC). The study consisted of 62 patients with esophageal cancer who underwent surgery between 2001 and 2007. The expression of the GADD45A gene product (GADD45A) and the p53 protein was analyzed by immunohistochemistry. The correlations among GADD45A expression, clinicopathological factors and prognosis were then analyzed in the patients with ESCC. GADD45A and p53 were expressed in 56.5% (35/62) and 48.4% (30/62) of patients, respectively. The expression of GADD45A did not show a marked correlation with that of p53. However, GADD45A expression correlated with pathological stage (stage 0-I vs. stages II-IV; P=0.014) and did not correlate with the tumor (T) or node (N) status. Furthermore, patients who were positive for GADD45A exhibited a significantly higher survival rate than those who were negative for GADD45A (log-rank test, P=0.009). Multivariate analysis indicated that T status, N status and GADD45A expression were significant variables predicting survival (hazard ratio, 2.486; 95% confidence interval, 1.168-5.290; P=0.018). Overall, GADD45A expression significantly affected the survival of patients with ESCC, and the reduced expression of GADD45A was correlated with a poor prognosis following curative surgery in these patients. PMID- 26870204 TI - Giant recurrent dumbbell-shaped hypoglossal schwannoma in an elderly male: A case report. AB - Dumbbell-shaped hypoglossal Schwannomas of the 12th cranial nerve are extremely rare, and complete removal of these tumors is difficult, particularly in elderly patients with recurrent tumors. The present study reports the case of a 61-year old male with a giant recurrent dumbbell-shaped hypoglossal schwannoma that arose extracranially. The recurrent tumor was completely removed in a one-stage surgical procedure via the far lateral suboccipital approach in combination with the transcervical approach. To the best of our knowledge, such a lesion has not been reported previously. The life expectancy and natural course of the disease are important factors to take into account when considering the individual end point of surgery in patients. More studies on hypoglossal schwannomas are required, particularly cases in which the hypoglossal schwannoma was not totally resected, not only in order to develop more definitive and secure surgical treatments, but also to reduce the resultant unnecessary suffering of patients. PMID- 26870205 TI - Recombinant adenovirus expressing hIFN-lambda1 inhibits gastric adenocarcinoma cell line SGC-7901 proliferation. AB - The aim of the present study is to investigate the effect of a recombinant plasmid adenovirus (pAd) expressing human interferon-lambda1 (hIFN-lambda1) on the proliferation of the gastric adenocarcinoma cell line SGC-7901. For this purpose, human gastric adenocarcinoma SGC-7901 cells were infected with recombinant pAd-hIFN-lambda1, pAd-LacZ and phosphate-buffered saline (PBS), respectively, and the subsequent effects on the proliferation of the infected cells were compared. Cell proliferation was evaluated by MTT assay, while mRNA and protein expression of hIFN-lambda1 were detected by reverse transcription polymerase chain reaction analysis and immunofluorescence assay, respectively. In addition, terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay and flow cytometry were conducted to analyze the rate of cell apoptosis. The results indicated that the proliferation of gastric adenocarcinoma SGC-7901 cells was significantly inhibited by pAd-hIFN-lambda1. Furthermore, the apoptosis rate and the mRNA and protein expression levels of hIFN-lambda1 were higher in pAd-hIFN-lambda1-transfected cells, compared with the pAd-LacZ and PBS control groups. In conclusion, recombinant pAd-hIFN-lambda1 induced the expression of hIFN-lambda1 in gastric adenocarcinoma SGC-7901 cells, and significantly inhibited cell proliferation by promoting apoptosis in these cancer cells. PMID- 26870206 TI - Expression of high mobility group box 1 protein predicts a poorer prognosis for patients with osteosarcoma. AB - The high mobility group box 1 (HMGB1) protein functions as an extracellular signaling molecule that is critical in inflammation and carcinogenesis. The HMGB1 protein is actively secreted by natural killer cells, monocytes and macrophages, and acts as an inflammatory cytokine. The present study enrolled 174 patients that underwent a tumorectomy between 2006 and 2013 in Shandong Provincial Hospital. The age of the patients ranged between 13 and 74 years, with a median age of 27 years. The tumors of the patients were staged according to the Union for International Cancer Control 2009 tumor-node-metastasis tumor staging system. Nuclear grading was based on the Fuhrman grading system. In the osteosarcoma tissue samples, HMGB1 expression was detected in 84 samples (48.3%) with a low immunoreactivity and in 90 samples (51.7%) with a high immunoreactivity. The association between clinicopathological characteristics and tumor cell HMGB1 expression (low vs. high) was summarized. The association between HMGB1 expression and tumor size, tumor stage and nuclear grade was statistically significant (P=0.034, 0.008 and 0.019, respectively). There was no significant association between HMGB1 expression and the age of the patients (P=0.335; Table I). The current study demonstrated that patients with a high HMGB1 expression (>50% cells expressing HMGB1) had poorer survival rates, and therefore a poorer prognosis, compared with patients with low HMGB1 immunostaining (10-50% cells expressing HMGB1). The results of the present study suggest that higher expression levels of HMGB1 are significantly associated with a poorer prognosis and may act as a marker for prognosis in osteosarcoma, particularly osteosarcoma recurrence. Additional studies investigating the biological features of HMGB1 may confirm the potential role of HMGB1 as a novel target for anticancer therapy in osteosarcoma. PMID- 26870207 TI - Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study. AB - Although adjuvant platinum-based chemotherapy has been demonstrated to improve survival in patients with completely resected non-small cell lung cancer (NSCLC), individualized approaches to therapy are urgently required to improve the treatment efficacy and reduce unnecessary toxicity. It was hypothesized in the present study that the protein levels of excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase M1 (RRM1) and class III beta-tubulin (TUBB3) may influence the therapeutic effect of adjuvant cisplatin-based chemotherapy. The expression of ERCC1, BRCA1, RRM1 and TUBB3 in tissues obtained from 84 patients with NSCLC was analyzed in the present non interventional study by immunohistochemistry prior to adjuvant chemotherapy. All patients received adjuvant cisplatin-based chemotherapy. The primary endpoint in the present study was disease free survival (DFS). Out of the 84 tumors, the expression of ERCC1, BRCA1, RRM1 and TUBB3 was identified in 46 (55%), 11 (13%), 73 (87%) and 76 (90%) tissues, respectively. A beneficial response to adjuvant cisplatin-based chemotherapy in DFS was associated with the absence of the expression of ERCC1 [hazard ratio (HR), 2.166; 95% confidence interval (CI), 1.049-4.474; P=0.037] and BRCA1 (HR, 2.419; 95% CI, 1.127-5.193; P=0.023), but not with the expression status of RRM1 (HR, 0.568; 95% CI, 0.234-1.379; P=0.212) or TUBB3 (HR, 1.874; 95% CI, 0.448-7.842; P=0.39). In addition, patients lacking the expression of ERCC1 and BRCA1 benefited more from adjuvant cisplatin-based chemotherapy compared with patients that expressed either ERCC1 or BRCA1 (HR, 3.102; 95% CI, 1.343-7.163; P=0.008). The expression of ERCC1 and BRCA1 was significantly associated with the DFS time in patients with NSCLC treated with adjuvant cisplatin-based chemotherapy, respectively. The combination of the ERCC1 and BRCA1 expression levels may be a promising prognostic prediction for adjuvant cisplatin-based chemotherapy. PMID- 26870208 TI - Slug overexpression is associated with poor prognosis in thymoma patients. AB - Slug, a member of the Snail family of transcriptional factors, is a newly identified suppressive transcriptional factor of E-cadherin. The present study investigated the expression pattern of Slug in thymomas to evaluate its clinical significance. Immunohistochemistry was used to investigate the expression pattern of the Slug protein in archived tissue sections from 100 thymoma and 60 histologically normal thymus tissue samples. The associations between Slug expression and clinicopathological factors, such as prognosis, were analyzed. Positive expression of Slug was detected in a greater proportion of thymoma samples [51/100 (51%) patients, P<0.001] compared with normal thymus tissues [9/60 (15%) cases]. Of the 100 patients with thymoma, 42 (42%) displayed high levels of Slug expression (high-level group) and 58 (58%) displayed low levels of Slug expression (low-level group). The 10-year survival rate was improved for patients in the low-level group when compared with those in the high-level group (P=0.002). A multivariate analysis using the Cox proportional hazards regression model demonstrated that Slug overexpression was not an independent prognostic factor. In conclusion, the present study demonstrated that Slug overexpression was associated with poor prognosis in patients with thymoma. Therefore, Slug may be a potential diagnostic biomarker and a predictor of poor prognosis in thymoma patients. PMID- 26870209 TI - Periosteal osteosarcoma and Marfan's syndrome: A case report and literature review. AB - Periosteal osteosarcoma (POS) is a rare primary malignant bone tumor arising from the surface of long bones. In addition, Marfan's syndrome (MFS) is an infrequent hereditary autosomal dominant connective tissue disorder with high penetrance and variable phenotypes, which primarily affects the ocular, skeletal and cardiovascular systems. The present study reported a case of POS and MFS co occurring in a child. A 6-year-old girl with MFS presented with pain, swelling and deformity in the right thigh following a fall. The patient was diagnosed with a right femoral shaft fracture and underwent open internal fixation surgery at a local hospital. At 2 weeks following surgery, the patient's parents observed increased swelling in the right thigh and thus, revisited the clinic. X-ray examination revealed extensive osteotylus around the fracture site and the clinician decided to remove the internal fixation. Following removal of the implant, aggravated swelling and superficial venous engorgement were observed. The patient was then admitted to Nanfang Hospital, where magnetic resonance imaging was performed, which identified symptoms of an abnormal periosteal reaction with bone erosion, indicating POS. The patient underwent a wide resection of the tumor and the histopathological examination confirmed the diagnosis of POS. No recurrence was identified at 9 months postoperatively. In conclusion, the present case report may result in increased awareness of the possibility of malignant bone tumors in a hereditary patient with osteotylus overgrowth following fracture surgery; in addition, the present case indicated a possible correlation between POS and MFS. PMID- 26870210 TI - 18F-fluorodeoxyglucose PET/CT for detection of disease in patients with prostate specific antigen relapse following radical treatment of a local-stage prostate cancer. AB - The present study aimed to retrospectively review the contribution of 18F fluorodeoxygluose-positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of biochemical recurrence in patients with a diagnosis of local-stage prostate cancer (PCa) who underwent radical prostatectomy (RP) or received external beam radiation therapy (EBRT). A total of 28 patients who underwent RP or received EBRT for PCa between July 2007 and April 2013, and who underwent 18F-FDG PET/CT scanning for re-staging due to biochemical recurrence were included in the present study. The mean age of the patients was 65.07 years and the standard deviation was 7.51 years (range, 51-82 years). Of the 28 patients, 23 (82.1%) underwent RP and 5 (17.9%) received definitive EBRT. Prior to scanning, all patients were required to fast for 6 h, and ~1 h after the intravenous injection of 555 MBq 18F-FDG, whole-body PET scans were performed from the skull base to the upper thighs. Whole-body CT scans were performed in the craniocaudal direction. 18F-FDG PET images were reconstructed using CT data for attenuation correction. Histopathology examination or clinical follow-up was used to confirm any suspicious recurrent or metastatic lesions. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT were 61.6, 75.0, 61.6, 75.0 and 71.4%, respectively. 18F-FDG PET/CT can detect local and distant metastases with a high accuracy in the assessment of biochemical recurrence, thus detecting occult metastases and allowing the re-staging of PCa in the patients receiving definitive treatment. It is considered that 18F-FDG PET/CT may be useful in re-assessing the patients with PCa receiving definitive treatment. PMID- 26870211 TI - Molecular determinants for lymph node metastasis in clinically early-stage endometrial cancer. AB - Patients with occult lymph node metastasis in endometrioid-type endometrial cancer (EC) are prone to the development of recurrences and have worse outcomes compared with patients without lymph node metastasis. In the current study, the aim was to identify molecular parameters associated with lymph node metastasis in EC clinically early-stage disease. A univariate analysis of differentially expressed genes, proteins and clinicopathological parameters (including myometrial invasion and tumor grade) was performed, comparing EC patients with and without lymph node metastasis (n=262 patients from The Cancer Genome Atlas). Significant parameters were introduced in a multivariate model and a gene expression pathway analysis. Lymph node metastasis was associated with expression of 268 unique genes (P<0.001), 19 unique proteins (P<0.05), tumor grade and myometrial invasion in univariate analysis. Multivariate analysis demonstrated 10 genes independently associated with lymph node metastasis and 4 independently associated proteins. Myometrial invasion was the only independent clinicopathological parameter associated with lymph node status. The enrichment pathway analysis demonstrated that expression of epidermal growth factor receptor, Bcl2 antagonist of cell death and phosphatase and tensin homolog pathways were significantly involved in lymph node metastasis (P<=0.001). A gene expression signature to predict lymph node status in EC was created for future validation. Few studies have focused on the association between EC's molecular characteristics and nodal metastasis. Defining molecular risk factors for EC lymphatic nodal metastasis may help to individualize treatment and improve patient outcomes. PMID- 26870213 TI - Mesonephric carcinoma of the uterine corpus: A report of two cases. AB - Mesonephric carcinoma of the uterine corpus is an extremely rare malignancy that originates from the mesonephric remnant of the female reproductive tract. There have been no previous reports of mesonephric carcinoma accompanied by a sarcomatous component. The current study presents two cases of uterine corpus mesonephric carcinoma with sarcomatous components that occurred in postmenopausal women. Immunohistochemically, the tumour cells were positive for vimentin and CD10. The tumours of these patients were located in the uterine myometrium; therefore, treatment was similar to that for endometrial cancer. Although the follow-up period was short in the current cases, no metastatic disease was identified in the second case and thus, this may increase clinical knowledge with regard to the biological behavior of these rare malignancies. PMID- 26870212 TI - Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis. AB - Epstein-Barr virus-induced gene 3 (EBI3) encodes a secretory glycoprotein, and has previously been identified as upregulated in a series of cancers. However, the clinical significance of EBI3 in cervical cancer and the potential of EBI3 as a therapeutic target for this disease have not been elucidated. In the present study, EBI3 expression was analyzed by immunohistochemistry in 90 clinicopathologically characterized cervical cancer tissue samples. The association between EBI3 expression and survival of patients with cervical cancer was also analyzed. The expression level of EBI3 in cervical cancer tissues was found to be significantly increased compared with the expression levels in the normal squamous epithelium. In addition, EBI3 expression was significantly correlated with the clinical stage and size of tumors (P<0.05). Furthermore, the presence of EBI3 expression was associated with a poor prognosis compared with patients without EBI3 expression. Multivariate analysis revealed that EBI3 expression was an independent predictor of overall survival (hazard ratio, 4.032; 95% confidence interval, 1.538-7.436; P=0.035). To the best of our knowledge, the present results indicate for the first time that EBI3 expression is significantly associated with the progression and poor prognosis of cervical cancer. EBI3 may be a potential prognostic marker and a therapeutic target in cervical cancer. PMID- 26870214 TI - Angiotensin II type 2 receptor-interacting protein 3a suppresses proliferation, migration and invasion in tongue squamous cell carcinoma via the extracellular signal-regulated kinase-Snai2 pathway. AB - Our previous studies demonstrated that the downregulation of microtubule associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein (MTUS1/ATIP) is associated with poor differentiation and prognosis in tongue squamous cell carcinoma (TSCC), and that ATIP1 exerts an antiproliferative effect on TSCC. The aim of the present study was to further investigate the anticancer effect of MTUS1/ATIP3a in TSCC. It was observed that UM1 cells (a TSCC cell line with high migration and invasion ability) exhibited lower expression of ATIP3a compared with UM2 cells (a TSCC cell line with lower migration and invasion ability). Restoration of ATIP3a expression in UM1 cells exerted antiproliferative effects and inhibited migration and invasion, whereas knockdown of ATIP3a promoted proliferation, migration and invasion in UM2 cells. Restoration of ATIP3a expression inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and the expression of Snai2 and vimentin in UM1 cells, whereas knockdown of ATIP3a promoted the phosphorylation of ERK1/2 and the expression of Snai2 and vimentin in UM2 cells. Therefore, MTUS1/ATIP3a was found to suppress the proliferation, migration and invasion of TSCC cells via the ERK1/2-Snai2 pathway. PMID- 26870215 TI - Expression of microRNA-10a, microRNA-342-3p and their predicted target gene TIAM1 in extranodal NK/T-cell lymphoma, nasal type. AB - MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes in different types of human cancer. T-lymphoma invasion and metastasis inducing factor 1 (TIAM1) participates in the development of several types of human cancer. However, the expression of miRNAs and TIAM1 in extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTCL) remains poorly understood. In the present study, the association between the expression levels of miR-10a and miR-342-3p and the protein expression levels of TIAM1 was examined in ENKTCL tissues. The expression levels of miR-10a, miR-22, miR-340, miR-342-3p and miR-590-5p in 15 primary ENKTCL tissues were analyzed using quantitative polymerase chain reaction, and the protein expression levels of TIAM1 in 21 primary ENKTCL tissues were analyzed using immunohistochemistry. The expression levels of miR-10a and miR-342-3p were lower in ENKTCL tissues than in normal NK cells, but no significant differences were observed in the expression levels of miR-22, miR-340 and miR-590-5p in ENKTCL tissues, compared with normal NK cells. The low expression levels of miR-10a detected in the tissues of patients with ENKTCL were inversely correlated with the age of the patients, whereas the low expression levels of miR-342-3p measured in these samples were not correlated with any demographic or clinical features of the patients. The protein expression levels of TIAM1 were higher in ENKTCL tissues than in normal and reactive lymph node hyperplasia tissues, and positively correlated with the Ann Arbor stage and international prognostic index score of the tumors. Furthermore, the expression levels of miRNA-10a and miRNA-342-3p were inversely correlated with the protein expression levels of TIAM1 in ENKTCL tissues. These data suggest that TIAM1 may contribute to the pathogenesis of ENKTCL, and miRNA-10a and miRNA-342-3p may be involved in the development of ENKTCL via the TIAM1 pathway. PMID- 26870216 TI - A metanephric adenoma of the kidney associated with polycythemia: A case report. AB - Metanephric adenoma (MA) of the kidney is a rare and frequently benign tumor with a favorable prognosis that is often diagnosed following surgical treatment. In the present study, a 54-year-old female patient presented with complaints of intermittent right-flank pain and anterior abdominal pain occurring over 2 years and sporadic gross hematuria occurring over 3 months. Ultrasonography and computerized tomography imaging revealed a neoplasm lesion localized in the right kidney. Successful open approach radical nephrectomy was performed and post surgical histopathological examination verified the lesion as a MA of the kidney. Radical nephrectomy, cryoablation or radiofrequency may used to treat MA and a selective panel of immunostains, including WT1, EMA and AMACR, may be useful for diagnosis. PMID- 26870217 TI - Efficacy and safety of homoharringtonine plus cytarabine and aclarubicin for patients with myelodysplastic syndrome-RAEB. AB - The aim of the present study was to evaluate the treatment outcome of homoharringtonine, cytarabine (AraC) and aclarubicin combination therapy as induction treatment for myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB). A total of 24 patients with MDS-RAEB who were aged between 18 and 66 years were treated with homoharringtonine, AraC and aclarubicin (HAA regimen). The HAA regimen consisted of homoharringtonine (2 mg/m2 intramuscularly twice daily, days 1-3), AraC (75 mg/m2 injected subcutaneously twice daily, days 1-7) and aclarubicin (12 mg/m2, days 1-7). The overall response rate was 79% with a complete remission rate of 58.3% and partial remission rate of 20.7%. There was no evidence of early mortality in this group of patients. The median overall survival (OS) was 36.2 months (95% confidence interval, 24.6-47.4 months), and the estimated three year overall survival rate was 45.8%. In conclusion, HAA combination therapy is a suitable induction regimen for patients with MDS-RAEB, which may improve the outcome for de novo higher-risk MDS patients, particularly of those with favorable and intermediate cytogenetics. PMID- 26870218 TI - CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression. AB - Chemokines and their receptors have been shown to contribute to tumor growth and metastatic spread in various gastrointestinal cancer entities. In the present study, the mRNA expression profiles and clinical significance of chemokine ligand CXCL12 and its corresponding receptor CXCR4 were investigated in patients with gastric cancer (GC). Using quantitative polymerase chain reaction, the expression profile of CXCL12/CXCR4 was analyzed in resection specimens from the patients with GC (n=66) and in corresponding normal gastric tissues. Upon investigating CXCL12/CXCR4 mRNA expression levels in the GC tissues, significant downregulation of CXCL12 expression was demonstrated (P<0.05), whereas CXCR4 mRNA expression was shown to be significantly upregulated (P<0.05). Likewise, in gastric carcinoma patients undergoing neoadjuvant chemotherapy, CXCR4 expression was found to be significantly upregulated (P<0.05), whereas in GC patients with lymph and vein infiltration, CXCL12 mRNA expression was significantly downregulated (P<0.05). These results demonstrate a significant inverse association between the development and progress of GC and CXCL12/CXCR4 mRNA expression. CXCR4 mRNA upregulation was promoted under the effect of neoadjuvant chemotherapy prior to surgery in GC patients, whereas higher tumor stages with lymph and vein infiltration negatively affected CXCL12 mRNA expression. PMID- 26870219 TI - Overexpression of MCPH1 inhibits uncontrolled cell growth by promoting cell apoptosis and arresting the cell cycle in S and G2/M phase in lung cancer cells. AB - Microcephalin (MCPH1/BRIT1) is a large nuclear protein that is involved in the early cellular response to DNA damage, the expression of which is reduced in a variety of types of human tumors. A recent study by our group demonstrated that MCPH1 expression is markedly decreased in lung cancer. However, it remains unclear whether inducing the expression of MCPH1 may ameliorate lung cancer, and, if so, which mechanisms underlie this process. The results of the present study demonstrated that MCPH1 expression was downregulated in lung cancer tissues compared with that in normal lung tissues. Furthermore, MCPH1 overexpression in A549 non-small cell lung carcinoma cells, successfully inhibited cell proliferation via arrest of the cell cycle in the S and G2/M phases. In addition, MCPH1 overexpression promoted cell apoptosis, in association with a significant increase in the quantities of Bax and active caspase-3, as well as a decrease in the level of Bcl-2. In conclusion the present results indicated that MCPH1 is involved in the regulation of apoptosis and entry into mitosis, suggesting that MCPH1 may function as a tumor suppressor and that it may be important in the pathogenesis of lung cancer. PMID- 26870220 TI - Quantitative assessment of the association between glutathione S-transferase M1 polymorphism and the risk of developing nasopharyngeal cancer. AB - Glutathione S-transferases (GSTs) participate in the detoxification and elimination of electrophilic carcinogens by conjugating them to glutathione. Previous studies have reported a potential association between GSTM1 polymorphism and the risk of developing nasopharyngeal cancer (NPC). However, those findings remain controversial. In the present study, a meta-analysis was conducted by pooling the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) of all the available case-control studies on NPC. A comprehensive search of PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases up to May 13th, 2014 was performed to identify eligible studies. A total of 12 separate publications, involving 1,593 cases of NPC and 2,868 controls, were included in the meta-analysis. The results demonstrated that the null genotype of GSTM1 was significantly associated with increased risk of developing NPC (OR=1.530, 95% CI=1.348-1.737, Pheterogeneity=0.370). Subgroup analysis by ethnicity suggested that Asian carriers of the GSTM1 null genotype were more susceptible to NPC than individuals from other ethnic groups (OR=1.516, 95% CI=1.328-1.731, Pheterogeneity=0.270). Sensitivity analysis confirmed the stability of these observations. In conclusion, the results from the present meta analysis indicated that the GSTM1 polymorphism may be involved in the development of NPC, particularly in Asians. PMID- 26870221 TI - Analysis of factors affecting endocrine therapy resistance in breast cancer. AB - The present study aimed to identify the factors involved in the resistance to endocrine therapy in breast cancer (BC) patients with a positive estrogen receptor status via the collection of clinical, pathological and immunohistochemical indices. A retrospective survey was performed in patients who experienced the relapse and metastasis of BC between November 2007 and March 2013. A total of 45 patients were enrolled, and the observational duration was 7 84 months. The Kaplan-Meier method was used to create a survival curve, while the log-rank test was used to analyze the survival curve and the Cox regression analysis was used to investigate the associated factors contributing to the resistance to endocrine therapy. Univariate analysis showed that the age of onset, the use of radiotherapy, the endocrine treatment program, and the expression levels of progesterone receptor (PR) and CerbB2 affected the impact of endocrine treatment. The Cox regression analysis indicated that the age of onset, the use of radiotherapy, and the expression levels of PR and CerbB2 affected the disease-free survival time after endocrine therapy. A young age of onset, not receiving radiotherapy, a low expression level of PR and a high expression level of CerbB2 were the risk factors involved in the resistance to endocrine therapy in patients with BC. PMID- 26870222 TI - Signal transduction by M3 muscarinic acetylcholine receptor in prostate cancer. AB - The present study aimed to investigate the potential mechanisms used during signal transduction by M3 muscarinic acetylcholine receptor (CHRM3) in prostate cancer. The microarray datasets of GSE3325, including 5 clinically localized primary prostate cancers and 4 benign prostate tissues, were downloaded from the Gene Expression Omnibus database. The differentially-expressed genes (DEGs) in primary prostate cancer tissues compared with benign controls were screened using the Limma package. Gene Ontology and pathway enrichment analyses were performed using the Database for Annotation Visualization and Integrated Discovery. Next, a protein-protein interaction (PPI) network was constructed. Additionally, microRNAs (miRNAs) associated with DEGs were predicted and miRNA-target DEG analysis was performed using a Web-based Gene Set Analysis Toolkit. Finally, the PPI network and the miRNA-target DEG network were integrated using Cytoscape. In total, 224 DEGs were screened in the prostate cancer tissues, including 113 upregulated and 111 downregulated genes. CHRM3 and epidermal growth factor (EGF) were enriched in the regulation of the actin cytoskeleton. EGF and v-myc avian myelocytomatosis viral oncogene homolog (Myc) were enriched in the mitogen activated protein kinase (MAPK) signaling pathway. EGF with the highest degree of connectivity was the hub node in the PPI network, and miR-34b could interact with Myc directly in the miRNA-target DEG network. EGF and Myc may exhibit significant roles in the progression of prostate cancer via regulation of the actin cytoskeleton and the MAPK signaling pathway. CHRM3 may activate these two pathways in prostate cancer progression. Thus, these two key factors and pathways may be crucial mechanisms during signal transduction by CHRM3 in prostate cancer. PMID- 26870223 TI - Epidermal growth factor receptor exon 20 p.S768I mutation in non-small cell lung carcinoma: A case report combined with a review of the literature and investigation of clinical significance. AB - Epidermal growth factor receptor (EGFR) plays a significant role in non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer worldwide. Therefore, EGFR may be a useful molecular target for personalized therapy utilizing tyrosine kinase inhibitors (TKIs). Somatic activating EGFR mutations may be used to identify tumors sensitive to the effects of small-molecule EGFR TKIs (gefitinib and erlotinib), and alternative, less frequently observed mutations, including the majority of mutations identified within exon 20, may be associated with a lack of response to TKIs. However, due to the comparative rarity of EGFR exon 20 mutations, clinical information concerning the association between EGFR exon 20 mutations and responsiveness to TKIs has been limited within the relevant literature, particularly for certain rare mutations, including p.S768I. The current study reports the case of a patient with NSCLC harboring a p.S768I mutation in the EGFR gene [a substitution at codon 768 of exon 20 (c.2303G>T, p.S768I)], as well as a mutation at codon 719, exon 18 (p.G719A). The relevant literature concerning this rare EGFR somatic mutation is also reviewed. PMID- 26870224 TI - Immunohistochemical expression of vascular endothelial growth factor in canine oral squamous cell carcinomas. AB - Angiogenesis is crucial for the growth and metastasis of malignant tumours, and various proangiogenic factors promote this process. One of these factors is vascular endothelial growth factor (VEGF), which appears to play a key role in tumour angiogenesis. The aim of the present study was to assess whether VEGF expression is associated with angiogenesis, disease progression and neoplastic proliferation in canine oral squamous cell carcinoma (OSCC) tissue. VEGF immunoreactivity was quantified by immunohistochemistry in 30 specimens, including normal oral mucosa and OSCC tissues graded as well, moderately or poorly differentiated. VEGF expression was correlated with tumour cell proliferation, as assessed using the proliferating cell nuclear antigen (PCNA) marker and microvessel density (data already published). The present results revealed that VEGF and PCNA expression increased significantly between normal oral tissue and neoplastic tissue, and between well and moderately/poorly differentiated tumours. In addition, VEGF expression was strongly correlated with PCNA expression and microvessel density. It was concluded that VEGF may promote angiogenesis through a paracrine pathway, stimulating endothelial cell proliferation and, similarly, may induce tumour cell proliferation through an autocrine pathway. The present results suggest that the evaluation of VEGF may be a useful additional criterion for estimating malignancy and growth potential in canine OSCCs. PMID- 26870225 TI - MicroRNA-147 suppresses proliferation, invasion and migration through the AKT/mTOR signaling pathway in breast cancer. AB - The Akt/mTOR pathway is considered to be the most frequently aberrantly activated pathway in human tumors. It is activated in a variety of types of tumor, and is therefore an attractive target for study, including it's potential regulation by microRNAs. A number of microRNAs (miRs) have been demonstrated to target the Akt/mTOR pathway. A previous study reported that miR-147 targets the EGFR-driven cell-cycle protein network in breast cancer. EGFR serves a crucial role upstream to Akt/mTOR. To define the function and mechanism of miR-147 in breast cancer, the present study assessed miR-147 expression in a normal mammary epithelial cell line and three breast cancer cell lines, and observed that miR-147 expression was markedly low in the highly invasive cell line, MDA-MB-231. Ectopic expression of miR-147 in MDA-MB-231 resulted in a reduction of the phosphorylation of crucial molecules in the Akt/mTOR pathway and the proliferation, invasion and migration of the cell line was also reduced. The effects of miR-147 expression are similar to that of shRNA which is specifically designed to silence the expression of Akt. The findings of the present study indicate that miR-147 suppressed the proliferation, invasion and migration of breast cancer cells through targeting the Akt/mTOR signaling pathway. As a new microRNA targeting Akt/mTOR pathway. Using miR-147 may therefore provide an effective therapeutic approach to suppress tumorigenicity in breast cancer. PMID- 26870226 TI - Sinomenine, a COX-2 inhibitor, induces cell cycle arrest and inhibits growth of human colon carcinoma cells in vitro and in vivo. AB - Certain non-steroidal anti-inflammatory drugs may possess anti-tumorigenic effects in certain cancer cell types. Sinomenine (SIN) is an alkaloid from Sinomenium acutum, a Chinese medicinal plant that inhibits inflammatory reactions and that has been used in the treatment of neuralgia and rheumatic diseases. In this study, we investigated the anticancer effects of SIN against colorectal cancer in vitro and in vivo, as well as the underlying mechanisms. The effects of SIN on proliferation, cell cycle progression and cyclooxygenase (COX)-2 expression were examined in human colorectal cancer-derived SW1116 cells. The in vivo effects of SIN were examined in a model of SW1116 tumor xenograft growth in athymic nude mice. Changes in COX-2 expression induced by the biological effects of SIN were analyzed by western blot analysis. The effects of SIN treatment on G1 phase cell cycle regulators in xenografts were analyzed by immunohistochemistry. Our findings demonstrate that SIN inhibits the proliferation of SW1116 cells by promoting their accumulation in the G1 phase, with concomitant suppression of COX 2 expression. Time- and dose-dependent inhibition of tumor growth and reduced toxicity were observed in nude mice administered daily intraperitoneal injections of SIN at doses of 25, 50 and 100 mg/kg. SIN-treated tumors also exhibited reduced COX-2 expression, a marked increase in Cip1/p21 protein levels and a decrease in the levels of cyclin D1 and cyclin E. SIN may be an effective chemopreventive agent against colorectal cancer. The growth inhibitory properties of SIN against colorectal cancer may be mediated via a COX-2 inhibitory effect and cell cycle arrest in the G1 phase. PMID- 26870227 TI - Tongue lipoma in an older male: A case report and literature review of patients with tongue lipoma reported in China. AB - Lipoma is the most common benign tumor that occurs at any region where adipose tissue is present. However, as the tongue is devoid of adipocyte it is an extremely rare site for a lipoma to develop, particularly in China. The present study reports the presence of a tongue lipoma in a 78-year-old man that measured 2.2*2.0*1.5 cm and was located on the left ventral region of the tongue. The tumor was completely excised, and subsequent to 4 years of follow-up, there was no recurrence of the lesion. In addition, the present study reviewed the literature concerning tongue lipomas in China and analyzed 18 other cases of patients with tongue lipomas in the past 30 years, between 1 January 1985 and 31 December 2014. PMID- 26870228 TI - Circulating microRNA-125b and microRNA-130a expression profiles predict chemoresistance to R-CHOP in diffuse large B-cell lymphoma patients. AB - Numerous studies have reported the aberrant expression profiles of microRNAs (miRNAs) in diffuse large B-cell lymphoma (DLBCL), although very few of these studies were concerned with chemoresistance to R-CHOP in DLBCL patients. This study was designed to assess the correlation between circulating miRNA expression and chemoresistance and prognosis in DLBCL patients. At the start of the study, we demonstrated that miRNA expression levels in serum were significantly associated with those in formalin-fixed, paraffin-embedded tissues, which indicated that circulating miRNAs may be powerful, non-invasive biomarkers reflecting miRNAs levels isolated from tumor tissue. Then from eight potential drug-resistant miRNAs which were deregulated in DLBCL and which had been reported to be associated with drug resistance in other carcinomas, we screened out the circulating miR-125b and miR-130a, which may related to R-CHOP resistance. Dynamic monitoring of the levels of circulating miR-125b and miR-130a further demonstrated that they were involved in recurrence, progression and chemoresistance in DLBCL patients. Finally, we demonstrated that high miR-125b indicated poor prognosis, as patients with higher miR-125b levels had a shorter overall survival. To our knowledge, this is the first study demonstrating that miR-125b and miR-130a are associated with the risk of chemoresistance in DLBCL patients, and that dynamic monitoring of the levels of circulating miR-125b and miR-130a predicts the therapeutic response and disease status of DLBCL patients. PMID- 26870230 TI - Management of pathological femoral fracture secondary to breast cancer in pregnancy: A case report. AB - Bone metastasis resulting from breast cancer in pregnancy is rare. In the literature there are few reports regarding osteolytic lesions in pregnancy and no data on the treatment of such femoral fractures. The present study reports a case of a 29-week primigravida presenting with severe lumbosciatica in the left side, refractory to medical therapy. During neurosurgical examination a spontaneous pathological fracture of the left femur occurred. Damage control orthopedic principals were applied and a biopsy specimen from the femoral lesion was obtained, providing a diagnosis of metastases from breast adenocarcinoma. Cesarean section was performed at 32 gestational weeks. Following delivery, an internal fixator was placed in the left femur for definitive treatment of the fracture and staging of cancer was conducted. Subsequently, adjuvant treatment comprising left mastectomy and percutaneous radiofrequency thermoablation of the sacroiliac lesion were performed. A follow-up one-year following percutaneous radiofrequency thermoablation of the sacroiliac lesion detected no metastatic bone pain, and identified a stable sacroiliac lesion. PMID- 26870229 TI - MicroRNA-101 suppresses migration and invasion via targeting vascular endothelial growth factor-C in hepatocellular carcinoma cells. AB - MicroRNAs (miRNAs) are a class of non-coding RNAs 18-25 nucleotides in length, which play important roles in the regulation of cancer progression through gene silencing. miRNA (miR)-101 has been suggested to be associated with hepatocellular carcinoma (HCC). However, the detailed role of miR-101 in HCC metastasis and the underlying mechanism remain largely unclear. The present study demonstrated that the expression of miR-101 was significantly reduced in HCC tissues compared with that in matched normal adjacent tissues. miR-101 was also found to be downregulated in four HCC cell lines compared with its expression in a normal liver cell line. Vascular endothelial growth factor (VEGF)-C was further identified as a direct target of miR-101, and the protein expression of VEGF-C was downregulated by miR-101 in HepG2 HCC cells. Furthermore, the overexpression of miR-101 and the knockdown of VEGF-C significantly inhibited HepG2 cell migration and invasion, while restoration of VEGF-C reversed the inhibitory effect of miR-101 overexpression on HepG2 cell migration and invasion. Finally, the expression of VEGF-C was notably increased in HCC tissues and cell lines. These findings suggest that miR-101 exerts a suppressive effect on HCC cell migration and invasion, at least in part through the direct inhibition of VEGF-C protein expression. Therefore, the miR-101/VEGF-C axis may serve as a potential therapeutic target for HCC metastasis. PMID- 26870231 TI - Expression of stem cell markers nanog and PSCA in gastric cancer and its significance. AB - The present study aimed to determine the expression of stem cell markers Nanog compared with PSCA in gastric cancer tissues and adjacent normal tissues, and to investigate the association between tumor stem cells and initiation, progression, metastasis, and prognosis of gastric cancer. One hundred chemotherapy- and radiotherapy-naive patients with pathologically confirmed gastric cancer were enrolled from the General Surgery Department and Surgical Oncology Department of the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, P.R. China), between October 2011 and June 2013. Surgically resected specimens of cancer tissues and adjacent normal tissues (>5 cm from the boundary of cancerous component) were collected. The mRNA expression levels of Nanog and PSCA in those tissues was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The correlation between the expression of stem cell markers Nanog and PSCA in gastric cancer tissues and clinicopathological factors was analyzed. The qPCR results demonstrated that the relative expression of Nanog was increased in gastric cancer tissues compared with in the adjacent tissues (P<0.05); and relative expression of PSCA was reduced in gastric cancer tissues compared with adjacent tissues (P<0.05). The expression of Nanog and PSCA in gastric cancer tissues was associated with tumor differentiation. The expression of Nanog was increased in poorly-differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). The expression of PSCA was reduced in poorly differentiated and undifferentiated tumors compared with moderately- and well-differentiated tumors (P<0.05). However, the expression of Nanog and PSCA was not associated with age, gender, tumor size, TNM stage, depth of invasion, or lymph node metastasis. Therefore, Nanog and PSCA may have potential as molecular markers to reflect the differentiation status of gastric cancer. PMID- 26870232 TI - Helicobacter pylori-infected MSCs acquire a pro-inflammatory phenotype and induce human gastric cancer migration by promoting EMT in gastric cancer cells. AB - Accumulating clinical and experimental evidence has suggested that Helicobacter pylori (H. pylori) infection-associated gastric cancer (GC) is associated with high rates of mortality and serious health effects. The majority of patients succumb to H. pylori infection-associated GC due to metastasis. Mesenchymal stem cells (MSCs), which have multipotent differentiation potential, may be recruited into the tumor-associated stroma. MSCs are crucial components of the H. pylori infection-associated GC microenvironment, and may be critical for GC cell migration. In this study, an MSCs/H. pylori co-culture model was designed, and the effect of H. pylori-infected MSCs on the migration of GC cells was evaluated using a Transwell migration assay. H. pylori-infected MSC cytokine expression was evaluated using Luminex/ELISA. The expression of epithelial-mesenchymal transition (EMT) markers in the GC cells treated with supernatants from H. pylori infected MSCs were detected by western blot analysis. The results demonstrated that the interaction between MSCs and H. pylori may induce GC cell migration, through secretion of a combination of cytokines that promote EMT in GC cells. The expression of phosphorylated forms of nuclear factor-kappaB (NF-kappaB) was observed to be increased in MSCs by H. pylori. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate blocked the effects of H. pylori-infected MSCs on SGC-7901 human stomach adenocarcinoma cell migration. Overall, the results of the present study suggest that H. pylori-infected MSCs acquire a pro-inflammatory phenotype through secretion of a combination of multiple cytokines, a number of which are NF-kappaB-dependent. These cytokines enhance H. pylori infection associated GC cell migration by promoting EMT in GC cells. The results of the present study provide novel evidence for the modulatory effect of MSCs in the tumor microenvironment and provide insight into the significance of stromal cell involvement in GC progression. PMID- 26870233 TI - Epidural angiomatous meningioma of the thoracic spine: A case report. AB - Spinal epidural angiomatous meningiomas (AMs) are extremely rare lesions. Here, we report on a case of an epidural AM of the thoracic spine with chronic but severe cord compression. The patient underwent a T6-T8 laminectomy through the posterior approach. En bloc resection was achieved, and histopathological examination demonstrated an AM. Delayed paraplegia occurred 4 h postoperatively. The patient was treated with methylprednisolone, hyperbaric oxygen and rehabilitation. Gradually, over the next six months, the bilateral leg strength was improved compared with the preoperative status, and no tumor recurrence was noted. Although epidural AM is extremely rare, it should be included in the differential diagnosis of spinal epidural lesions. A definitive diagnosis is difficult based on magnetic resonance imaging alone due to the nonspecific characteristics of the tumor. Since AM is a histologically benign and highly vascularized tumor, timely gross total resection (GTR) is the most effective treatment. A good clinical outcome may be expected following GTR (Simpson grade I and II resection). PMID- 26870234 TI - Costimulation with anti-cluster of differentiation 3 and anti-cluster of differentiation 28 reduces the activity of mucin 1-stimulated human mononuclear cells. AB - Cytotoxic T-lymphocyte activation and extension of the cell life span is necessary in order to enable immunotherapy to perform effectively against cancer. In the present study, mucin 1 (MUC1)-stimulated human mononuclear cells (M1SHMCs) were costimulated with bead-attached monoclonal antibodies specific for cluster of differentiation (CD)3 and CD28 receptors. The study was undertaken to determine whether costimulation was capable of enhancing the killing of cancer cells in vitro and of protecting non-obese diabetic severe combined immunodeficient mice from tumor development. Lysis of MCF-7 tumor cells by M1SHMCs was reduced following costimulation with anti-CD3 and anti-CD28. Furthermore, costimulation with anti-CD3 and anti-CD28 eliminated the protective effects of M1SHMCs on MCF-7 breast cancer cell growth in the non-obese diabetic severe combined immunodeficient mice. The present study suggested that costimulation with anti-CD3 and anti-CD28 is not advisable following antigen activation of lymphocytes under the conditions used here. Using a lower anti CD3/CD28 bead to T-cell ratio may prevent immune suppression, however, further studies are required to support this hypothesis. PMID- 26870235 TI - Intramuscular myxoma of the paraspinal muscles: A case report and systematic review of the literature. AB - Intramuscular myxoma (IM) is a rare mesenchymal tumor of the head and neck region. The current study reports a case of a 45-year-old man who presented with a painless neck mass. Imaging showed involvement of the levator scapulae and scalene muscles. Core needle biopsy was consistent with intramuscular myxoma. Surgical excision was performed and follow-up for 30 months showed no recurrence. The present study includes a systematic review of head and neck IMs, with a summary of the clinical and demographic parameters of all reported cases in the head and neck region. Surgery was curative in 28 of the 29 published cases, as well as in the current case (96.7%), with the lone recurrent tumor cured following re-resection. Females constituted 57% of the cases and the mean age was 49.7+/-20.4 years. Although uncommon, IM should be considered in the differential diagnosis of deep neck masses, and surgical excision is the treatment of choice with a low risk of recurrence. PMID- 26870236 TI - The effects of buthionine sulfoximine on the proliferation and apoptosis of biliary tract cancer cells induced by cisplatin and gemcitabine. AB - Patients with biliary tract cancer (BTC) have a poor prognosis. Advanced BTC patients have been treated with cisplatin in combination with gemcitabine, however, the treatment has had little impact on survival rates, and more effective treatments are urgently required for this disease. Previous studies discovered that buthionine sulfoximine (BSO), a potent inhibitor of glutathione (GSH) synthesis, was able to enhance the cytotoxic effect of various drugs in cancer cells. Phase I studies demonstrated that continuous-infusion of BSO was relatively non-toxic and resulted in the depletion of tumor GSH. However, the synergistic effect of BSO and cisplatin in BTC cells remains unknown, and no reports are available regarding sensitization to gemcitabine by BSO. In the present study, the effect of BSO in combination with cisplatin or gemcitabine in the treatment of BTC cells was examined in vitro. Cytotoxic effects were measured using an MTT assay, Annexin V assay and fluorescence-activated cell sorting analysis. Antiapoptotic protein expression levels were examined using western blot analysis. The results revealed that a sub-toxic concentration of BSO was capable of significantly enhancing cisplatin-induced apoptosis in BTC cells. The mechanisms of BSO's effect on BTC cells may be attributable to the reduction of GSH levels and downregulation of the expression of antiapoptotic proteins (Bcl-2, Bcl-xL and Mcl-1). Furthermore, BSO enhanced the antiproliferative effect of gemcitabine. In conclusion, the present data are the first results to indicate that BSO may sensitize BTC cells to standard first-line chemotherapeutic agents (cisplatin and gemcitabine). Combining BSO with cisplatin and gemcitabine is a promising therapeutic strategy for the treatment of BTC. PMID- 26870237 TI - Peptic ulcers accompanied with gastrointestinal bleeding, pylorus obstruction and cholangitis secondary to choledochoduodenal fistula: A case report. AB - Peptic ulcers are an extremely common condition, usually occurring in the stomach and proximal duodenum. However, cases of peptic ulcers accompanied with multiple complications are extremely rare and hard to treat. The present case reinforces the requirement for the early recognition and correct treatment of peptic ulcers accompanied with multiple complications. A 67-year-old man presented with recurrent abdominal pain, fever and melena. The laboratory results showed anemia (hemoglobin 62 g/l) and hypoproteinemia (23 g/l). Abdominal imaging examinations revealed stones in the gallbladder and right liver, with air in the dilated intrahepatic and extrahepatic bile ducts. Endoscopic retrograde cholangiopancreatography failed due to a deformed pylorus. The patient was finally diagnosed with peptic ulcers accompanied with gastrointestinal (GI) bleeding, pylorus obstruction and cholangitis secondary to a choledochoduodenal fistula during an emergency pancreatoduodenectomy, which was performed due to a massive hemorrhage of the GI tract. The patient recovered well after the surgery. PMID- 26870238 TI - Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway. AB - Numerous studies have demonstrated that resveratrol has a potential use in cancer prevention and treatment. However, the effects of resveratrol on cancer cell motility and invasiveness remain unclear. The current study aimed to examine the effects of resveratrol on cell migration and invasion in human glioblastoma cells, and to explore the underlying molecular mechanisms. In wound-healing and Matrigel transwell assays, resveratrol was found to significantly inhibit the migration and invasion of U87MG, T98G and U251 glioblastoma cells in vitro. Results from western blot analysis and gelatin zymography revealed that resveratrol also suppressed the expression and activity of matrix metalloproteinase 2 (MMP-2; P<0.05), an important mediator of cell migration and invasion. Furthermore, using a pull-down assay, increased activation of RhoA was observed in glioblastoma cells treated with resveratrol vs. controls (P<0.05). Notably, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway by C3 transferase or Y-27362 was found to attenuate the resveratrol-induced reductions in cell migration and invasion (P<0.05), and also partially rescued the decreased expression and activity of MMP-2 induced by resveratrol (P<0.05). Taken together, the results suggest that resveratrol may inhibit glioblastoma cell motility and invasiveness via activating the RhoA/ROCK signaling pathway. PMID- 26870239 TI - Effect of CPU-XT-008, a combretastatin A-4 analogue, on the proliferation, apoptosis and expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells. AB - The present study investigated the effect of the combretastatin A-4 analogue CPU XT-008 on the proliferation, apoptosis and expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) in human umbilical vein endothelial cells (HUVECs). The proliferation capacity of HUVECs was analyzed with a cell viability assay, while their apoptosis and migration abilities were evaluated via flow cytometry and monolayer denudation assay, respectively. The mRNA and protein expression levels of VEGF and FGF-2 in these cells were determined by reverse transcription-polymerase chain reaction, and cell-based ELISA, western blotting and immunocytochemistry, respectively. The results demonstrated that CPU-XT-008 inhibited proliferation and migration, and induced apoptosis in HUVECs in a dose-dependent manner. In addition, CPU-XT-008 downregulated the mRNA and protein expression levels of VEGF and FGF-2 in these cells. These findings suggest that CPU-XT-008 exerts anti-angiogenic effects in HUVECs, which may explain the inhibition of cell proliferation and migration, induction of apoptosis, and reduction in the mRNA and protein expression levels of VEGF and FGF-2 observed in the present study. PMID- 26870241 TI - Recurrence rate and progression of chondrosarcoma is correlated with heat shock protein expression. AB - Heat shock proteins (HSPs) are involved in tumour immunity, and are correlated with survival and drug resistance in numerous types of cancer. The present study investigated the expression of HSPs and multiple drug resistance (MDR) in human chondrosarcoma. HSP and P-glycoprotein (the MDR1 gene product) expression was evaluated by immunohistochemical analysis of paraffin-embedded sections obtained from 37 patients with chondrosarcoma (19 male and 18 female; aged 33-85 years; mean age, 48.5 years). HSP73 and 90 were significantly overexpressed in patients with local recurrence: HSP73 was expressed in 7/7 patients (100%) with local recurrence and 9/18 patients (50%) without recurrence (P<0.02), while HSP90 was expressed in all patients with recurrence but only 8/18 (44%) without recurrence (P<0.02). A marked association was also identified between HSP expression and survival. HSP72 and 73 were significantly overexpressed in tumours from patients who succumbed to the disease (all positive for HSP72 and 73; P<0.05). No differences were observed between HSP27, 73 or 90-positive or -negative tumours according to age or gender. In addition, HSP72 expression was correlated with differentiation of the tumours (P<0.02). These results indicate that HSP72, 73 and 90 may function as novel prognostic markers for chondrosarcoma, and initiate further studies regarding the use of such markers for the identification of patients with poor prognosis. PMID- 26870240 TI - Immunosuppression of breast cancer cells mediated by transforming growth factor beta in exosomes from cancer cells. AB - Exosomes derived from tumor cells are essential for processes involved in tumor progression, including angiogenesis, tumor cell proliferation and immunoregulation. In addition, exosome secretion may contribute to the mechanisms of hypoxia-induced angiogenesis and metastasis of tumors. In the present study, as it is one of the most common cancers in females, breast cancer, cell lines were cultured under hypoxic (1% O2) and normoxic conditions to evaluate the effects of hypoxia on exosome production. Under hypoxic conditions an increase in the number of exosomes in the medium, determined by CD63 immunoblotting, was observed. Application of these exosomes to T cells revealed that they were able to suppress T cell proliferation. As transforming growth factor-beta (TGF-beta), interleukin-10, and prostaglandin E2 are important factors in the mediation of T cell suppression, the exosomes were subsequently treated with antibodies against these three factors. The results revealed that anti-TGF-beta was capable of ameliorating the immunosuppressive effects of exosomes. These data demonstrate that hypoxia enhances the secretion of exosomes by breast cancer cells, which acts to suppress T cell proliferation via TGF-beta. The findings have significant implications for understanding the underlying mechanisms of immunosuppression in tumor microenvironments, and for the potential development of cancer therapies. PMID- 26870242 TI - Identification of key genes associated with gastric cancer based on DNA microarray data. AB - The present study aimed to identify genes with a differential pattern of expression in gastric cancer (GC), and to find novel molecular biomarkers for GC diagnosis and therapeutic treatment. The gene expression profile of GSE19826, including 12 GC samples and 15 normal controls, was downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) were screened in the GC samples compared with the normal controls. Two-way hierarchical clustering of DEGs was performed to distinguish the normal controls from the GC samples. The co-expression coefficient was analyzed among the DEGs using the data from COXPRESdb. The gene co-expression network was constructed based on the DEGs using Cytoscape software, and modules in the network were analyzed by ClusterOne and Bingo. Furthermore, enrichment analysis of the DEGs in the modules was performed using the Database for Annotation, Visualization and Integrated Discovery. In total, 596 DEGs in the GC samples and 57 co-expression gene pairs were identified. A total of 7 genes were enriched in the same module, for which the function was phosphate transport and which was annotated to participate in the extracellular matrix-receptor interaction pathway. These genes were collagen, type VI, alpha3 (COL6A3), COL1A2, COL1A1, COL5A2, thrombospondin 2, COL11A1 and COL5A1. Overall, the present study identified several biomarkers for GC using the gene expression profiling of human GC samples. The COL family is a promising prognostic marker for GC. Gene expression products represent candidate biomarkers endowed with great potential for the early screening and therapy of GC patients. PMID- 26870243 TI - Successful mucosal incision-assisted biopsy for the histological diagnosis of duodenal lymphoma: A case report. AB - Tissue sampling of primary duodenal lymphoma is essential for its histological diagnosis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is frequently used for submucosal tumor (SMT)-like duodenal tumors, is adequate for cytological diagnosis, but not for histological diagnosis. Therefore, in the present study, a mucosal incision-assisted biopsy (MIAB) was performed in an 81 year-old woman for the diagnosis of an SMT-like duodenal mass, as tissue sampling for histological analysis using a regular endoscopic biopsy had failed to establish a definite diagnosis of malignant lymphoma. EUS-FNA had also led to poor tissue sampling due to the difficult location of the duodenal tumor. The pathological examination of biopsy samples using MIAB revealed the presence of a diffuse proliferation of atypical lymphocytes, and the expression of cluster of differentiation (CD)20 and CD79a, but no expression of CD3 in the tumor specimens. The patient was diagnosed with diffuse large B-cell lymphoma. To the best of knowledge, this is first report of a case using MIAB as a sampling method for the histological diagnosis of SMT-like primary duodenal lymphoma. This case suggests that MIAB may be an essential method for obtaining tissue samples from SMT-like duodenal tumors. PMID- 26870244 TI - Integrin beta1-mediated acquired gefitinib resistance in non-small cell lung cancer cells occurs via the phosphoinositide 3-kinase-dependent pathway. AB - The present study aimed to explore the role of integrin beta1 and the relevant signaling pathways in acquired gefitinib resistance in non-small cell lung cancer (NSCLC). The inhibitory effects of gefitinib, with or without LY294002, on cellular proliferation were evaluated by 3-(4,5-dimethylthiazol-2-yl) 2,5 diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were analyzed by flow cytometry, while western blotting was used to evaluate the expression of EGFR, phosphorylated (phospho)-EGFR, protein kinase B (Akt), phospho-Akt, extracellular signal-regulated kinase (Erk) and phospho-Erk. The gene expression profiles of PC9 and PC9/G cells were determined by DNA microarray. Integrin beta1 was knocked down in PC9/G cells by transiently transfected short interfering RNA (siRNA). A scrambled siRNA sequence was used as a control. Apoptosis of transfected cells was determined by Annexin V phycoerythrin-Cy5/propidium iodide staining. Sequencing products were amplified by nested PCR. The resistant index of PC9/G cells to gefitinib was ~138- to 256 fold higher than that of PC9 cells, and this resistance was accompanied by significant increase in integrin beta1 expression in PC9/G cells. Knockdown of integrin beta1 with short hairpin RNA in PC9/G cells markedly inhibited proliferation and enhanced apoptosis in response to gefitinib, restoring the sensitivity of PC9/G cells gefitinib. Phosphoinositide 3-kinase (PI3K)/Akt activation was observed in PC9/G cells in the presence of gefitinib and the sensitivity of PC9/G cells to gefitinib was also able to be restored by PI3K/Akt pathway inhibitor LY294002. Finally, knockdown of integrin beta1 significantly reduced the levels of phospho-Akt. These findings suggest that integrin beta1 signaling via the PI3K/Akt pathway may be a significant mechanism underlying gefitinib resistance, and may potentially present an alternative therapeutic target for the treatment of NSCLC unresponsive to EGFR inhibitors. PMID- 26870245 TI - miR-135b inhibits tumour metastasis in prostate cancer by targeting STAT6. AB - MicroRNAs (miRNAs) are small non-coding RNAs that participate in several cellular functions and tumour progression. A previous microarray study demonstrated that miR-135b is downregulated in prostate cancer (PCa) cells, but the role and molecular mechanism of miR-135b in the regulation of tumour metastasis remain to be elucidated. In the present study, significant downregulation of miR-135b in PCa tissues, compared with noncancerous tissues, was detected by reverse transcription-quantitative polymerase chain reaction. Furthermore, the expression of miR-135b was demonstrated to be associated with the pathological stage and the levels of total and free prostate-specific antigen (PSA) in PCa cells. In addition, signal transducer and activator of transcription 6 (STAT6) was identified as a target of miR-135b in PCa cells by luciferase activity and western blot assays. The upregulation of miR-135b in PCa cells led to reduced expression of STAT6 in the cytoplasm and nucleus of these cells, while the overexpression of miR-135b and knockdown of STAT6 were able to inhibit the migration and invasion abilities of PCa cells in vitro. Therefore, the results of the present study indicate that miR-135b suppresses tumour metastasis by targeting STAT6. PMID- 26870246 TI - BRIP1 inhibits the tumorigenic properties of cervical cancer by regulating RhoA GTPase activity. AB - Breast cancer 1, early onset (BRCA1)-interacting protein 1 (BRIP1), a DNA dependent adenosine triphosphatase and DNA helicase, is required for BRCA associated DNA damage repair functions, and may be associated with the tumorigenesis and aggressiveness of various cancers. The present study investigated the expression of BRIP1 in normal cervix tissues and cervical carcinoma via reverse transcription-quantitative polymerase chain reaction (RT qPCR) and immunohistochemistry assays. BRIP1 expression was observed to be reduced in squamous cancer tissue and adenocarcinoma compared with normal cervix tissue, and there were significant correlations between the reduction in BRIP1 expression and unfavorable variables, including the International Federation of Gynecologists and Obstetricians stage and presence of lymph node metastases. In order to elucidate the role of BRIP1 in cervical cancer, a BRIP1 recombinant plasmid was constructed and overexpressed in a cervical cancer cell line (HeLa). The ectopic expression of BRIP1 markedly inhibited the tumorigenic properties of HeLa cells in vitro, as demonstrated by decreased cell growth, invasion and adhesion, and increased cell apoptosis. In addition, it was identified that the inhibitory tumorigenic properties of BRIP1 may be partly attributed to the attenuation of RhoA GTPase activity. The present study provides a novel insight into the essential role of BRIP1 in cervical cancer, and suggests that BRIP1 may be a useful therapeutic target for the treatment of this common malignancy. PMID- 26870247 TI - Expression of PTEN and KAI1 tumor suppressor genes in pancreatic carcinoma and its association with different pathological factors. AB - Pancreatic carcinoma is a common cancer type with a poor prognosis. The aim of the present study was to examine the expression of tumor suppressor genes phosphatase and tensin homolog deleted in chromosome 10 (PTEN) and KAI1 in pancreatic carcinoma and its association with clinical pathological factors. A total of 50 hospitalized cases of pancreatic cancer including 28 males and 22 females aged 31-82 years were included in the present study. Ten cases of normal pancreatic tissue were obtained from cadavers and served as the controls. The pancreatic specimens were embedded in paraffin blocks and slides were prepared for immunohistochemical analysis to determine the expression of PTEN and KAI1 in normal pancreatic tissue and pancreatic carcinoma samples. The positive expression rate of PTEN in the normal pancreatic tissue was higher than that in pancreatic carcinoma (P<0.05), while the positive expression rate of KAI1 in the normal pancreatic tissue was lower than that in pancreatic carcinoma (P<0.05). Pathological factors such as clinical stage of disease, histological grade and the presence or absence of lymphatic metastasis significantly affected the expression of PTEN and KAI1 (P<0.05). In conclusion, the positive expression of PTEN and KAI1 in pancreatic carcinoma is closely associated with the development of pancreatic carcinoma. PMID- 26870248 TI - Surgical resection of solitary omental metastasis from non-small cell lung cancer: Report of three cases. AB - In the present study we report three cases of solitary omental metastasis from non-small cell lung cancer, which had been surgically resected at our institute. The primary site was resected in one patient (case 1) and the other two patients were treated with chemotherapy and demonstrated complete response (cases 2 and 3). The omental metastasis appeared 4 months after pneumonectomy in case 1. Two metachronous omental tumors appeared 55 and 79 months after the initial chemotherapy in case 2. In Case 3, an omental tumor appeared 6 months after chemotherapy. Case 1 succumbed to recurrence 8 months after the resection of the omental tumor. Case 2 survives with recurrent disease 8 months after resection of the second omental metastasis, and case 3 survives 6 months after resection of the omental tumor. Although omental metastasis from non-small cell lung cancer is extremely rare, it should be considered when a patient with history of lung cancer has a tumor around the stomach. PMID- 26870250 TI - Expression profile of cathepsins indicates the potential of cathepsins B and D as prognostic factors in breast cancer patients. AB - Breast cancer is one of the most prevalent types of cancer in women and contributes to 32% of all female cancer cases. Cathepsins, a family of proteins, are known to have a critical role in human cancers. However, previous studies on the systematic analysis of the role of cathepsin family members in breast cancer are limited. The aim of the present study was to identify biological markers to predict prognosis and treatment response of breast cancer patients, as well as to elucidate novel therapeutic targets. The present study analyzed the expression of six members of cathepsin family, including cathepsins B, G, D, K, L and V in 188 breast cancer tissue specimens using immunohistochemistry. The data showed that all members of the tested cathepsin families featured cytoplasmic staining. Notably, expression of cathepsin L was associated with advanced tumor stages, while cathepsins B and K expression levels were associated with positive estrogen receptor expression; in addition, cathepsin K expression was also demonstrated to be associated with progesterone receptor expression. Cathepsins V and D expression levels were found to be associated with breast cancer metastasis, while the expression levels of cathepsins B and D were associated with poor disease-free survival in breast cancer patients. In addition, univariate analysis demonstrated that breast cancer metastasis to the bone and the expression of cathepsin B protein were associated with poor disease-free survival. In conclusion, the results of the present study indicated that the altered expression of cathepsins, in particular cathepsins B and D, contributed to the progression of breast cancer and poor disease-free survival in breast cancer patients. PMID- 26870249 TI - Identification of metastasis-associated genes in colorectal cancer using metaDE and survival analysis. AB - The aim of the present study was to detect the candidate genes involved in the metastasis of colorectal cancer (CRC). Gene expression profiles of primary and metastatic CRC samples in the GSE14297 and GSE49355 datasets were downloaded from the Gene Expression Omnibus database. Subsequent to processing, Fishers exact test and the metaDE package in R language were applied to screen the differentially expressed genes (DEGs) between primary and metastatic CRC samples. In addition, function and pathway enrichment analysis was performed using online tools in the Database for Annotation, Visualization, and Integrated Discovery resource and common DEGs in GSE14297 and GSE49355 were identified. Their expression values in another dataset, GSE29621, were then collected in order to screen the genes with high standard deviations between primary and metastatic samples, which were considered as candidate metastasis-associated genes. Candidate genes were finally verified by performing survival analysis via the log rank test. A total of 370 DEGs were screened in GSE14297 and GSE49355, and 77 common DEGs were identified. Upregulated DEGs were mainly enriched in the immune, energy metabolism and drug metabolism-associated functions. Downregulated DEGs were mainly enriched in cell adhesion-associated functions. A total of 12 genes, including the carbonic anhydrase II (CA2), carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7), Fc fragment of immunoglobulin G binding protein (FCGBP), and placenta-specific 8 (PLAC8), were the candidate metastasis associated genes, among which FCGBP expression significantly decreased the overall survival time of patients. The selected candidate metastasis-associated gene, FCGBP, may be used as a potential therapeutic target in patients with metastatic CRC. PMID- 26870251 TI - The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice. AB - Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials. PMID- 26870252 TI - Genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia cell line. AB - Thorough examination of genetic heterogeneity of cell lines is uncommon. In order to address this issue, the present study analyzed the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line. For this purpose, traditional techniques such as fluorescence in situ hybridization and immunocytochemistry were used, in addition to more advanced techniques, including cell sorting, Sanger sequencing and massive parallel sequencing. The results indicated that the RPMI-8402 cell line consists of several genetically different cell subpopulations. Furthermore, massive parallel sequencing of RPMI-8402 provided insight into the evolution of T-ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T-ALL. Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research. PMID- 26870253 TI - Sentinel lymph node biopsy in T1/T2 squamous cell carcinomas of the tongue: A prospective study. AB - Commonly used staging procedures often cannot predict the absence of cervical metastases (CM) in squamous cell carcinomas (SCCs) of the oral cavity. Due to the high incidence of occult CM in numerous N0 cases in the clinic, an elective neck dissection (ND) is performed. The sentinel lymph node biopsy (SNB) is a common concept in the modern surgical therapy of malignancies. The present study evaluates the applicability of this concept for T1/T2-SCC of the tongue. In a prospective clinical study, 10 consecutive patients with T1/T2-SCC of the tongue and cN0 necks, were enrolled. Following sentinel lymph node (SLN) scintigraphy, all patients underwent SNB with a gamma-probe and a subsequent ND. SNB specimens were compared with histopathological assessments of surgical specimens from the ND. A total of 5 female and 5 male patients (mean age, 52 years; women, 62 years; men, 42 years), with a median follow-up time of 33.5 months (range, 10-40 months), were treated. All patients presented with detectable SLNs. In 7 cases, the SLN(s) and the residual ND were negative for CM. In 3 cases, the SLN(s) were positive without further CM in the other neck nodes. Furthermore, 1 patient showed additional CMs after 10 months in the contralateral neck and lung metastasis after 18 months, but none at the time of the initial treatment. The concept of an SNB appears to be applicable to the management of the cN0 neck in small SCC of the tongue. The role of SNB in the management of SCC requires further investigation by prospective trials with larger patient numbers. PMID- 26870254 TI - Intraluminal superior vena cava metastasis from adenosquamous carcinoma of the duodenum: A case report. AB - In 2013, a 76-year-old male with a cardiac pacemaker was diagnosed with adenosquamous carcinoma of the duodenum. Subsequently, a pancreatoduodenectomy and lymph node dissection were performed, and 12 cycles of adjuvant chemotherapy (modified FOLFOX6 regimen), which consisted of fluorouracil, leucovorin and oxaliplatin, were administered via a central venous catheter. At 5 months after the completion of adjuvant chemotherapy, the patient experienced the sudden onset of severe pain at the back right of the ear, edema of the right side of the face and right jugular vein dilatation. Computed tomography (CT) revealed filling defects in the superior vena cava (SVC) and right brachiocephalic vein, indicating catheter-induced venous thrombosis. Although the catheter was removed and anti-coagulation therapy, aspiration of the thrombosis and ballooning dilatation were performed immediately, the patient's symptoms were not ameliorated. Notably, histological examination following thrombus aspiration revealed metastatic cancer cells, and fluorodeoxyglucose-positron emission tomography/CT identified metabolically active nodules in the SVC at locations consistent with the initial duodenal tumors detected by CT and in the first thoracic vertebrae. The tumor thrombus rapidly increased in size and resulted in worsening dyspnea. Subsequently, radiotherapy was performed, followed by chemotherapy, which relieved the systemic symptoms and suppressed the tumor growth. Adenosquamous carcinoma of the duodenum is extremely rare, and to the best of our knowledge, intraluminal SVC metastasis as a result of adenosquamous carcinoma of the duodenum has not been reported previously. The placement of a cardiac pacemaker, central venous catheter and tumor cells possessing high metastatic potential are hypothesized to have contributed to this rare case of metastasis. PMID- 26870255 TI - Melittin suppresses cathepsin S-induced invasion and angiogenesis via blocking of the VEGF-A/VEGFR-2/MEK1/ERK1/2 pathway in human hepatocellular carcinoma. AB - Melittin, a significant constituent of Apis mellifera (honeybee) venom, is a water-soluble toxic peptide that has traditionally been used as an antitumor agent. However, the underlying mechanisms by which it inhibits tumor cell growth and angiogenesis remain to be elucidated. In the present study, screening for increased cathepsin S (Cat S) expression levels was performed in MHCC97-H cells and various other hepatocellular carcinoma cell lines by reverse transcription polymerase chain reaction and western blot analysis. A pcDNA3.1-small hairpin RNA (shRNA)-Cat S vector was stably transfected into MHCC97-H cells (shRNA/MHCC97-H) in order to knockdown the expression of Cat S. The effects resulting from the inhibition of Cat S-induced proliferation, invasion and angiogenesis by melittin were examined using cell proliferation, cell viability, flat plate colony formation, migration, wound healing, Transwell migration and ELISA assays. In order to substantiate the evidence for melittin-mediated inhibition of Cat S induced angiogenesis, Cat S RNA was transfected into primary human umbilical vein endothelial cells (Cat S-HUVECs) to induce overexpression of the Cat S gene. The effects of melittin on HUVECs were examined using Transwell migration and tube formation assays. The findings demonstrated that melittin was able to significantly suppress MHCC97-H cell (Mock/MHCC97-H) proliferation, invasion and angiogenesis, as well as capillary tube formation of Cat S-HUVECs, in a dose dependent manner. However, proliferation, invasion and angiogenesis in shRNA/MHCC97-H and in native HUVECs (Mock-HUVECs) were unaffected. In addition, melittin specifically decreased the expression of phosphorylated (activated) Cat S, and components of the vascular endothelial growth factor (VEGF)-A/VEGF receptor 2 (VEGFR-2)/mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK)1/2 signaling pathway in Mock/MHCC97-H cells. In conclusion, the inhibition of tumor cell growth and anti angiogenic activity exerted by melittin may be associated with anti-Cat S actions, via the inhibition of VEGF-A/VEGFR-2/MEK1/ERK1/2 signaling. PMID- 26870256 TI - Novel method for the detection and quantification of malignant cells in the CSF of patients with leptomeningeal metastasis of lung cancer. AB - The aim of the present study was to discuss a novel method for the detection of malignant tumor cells in cerebrospinal fluid (CSF), by observing tumor marker immunostaining fluorescence in situ hybridization (TM-iFISH) enrichment and by counting CSF malignant tumor cells in patients with lung cancer leptomeningeal metastasis (LM). A total of 10 CSF samples were collected from 6 patients that presented with lung cancer LM. For each patient, 20 ml CSF was obtained through a lumbar puncture, of which 7.5 ml was used to count the number of malignant tumor cells in the CSF using TM-iFISH enrichment. Cytological and biochemical examinations were conducted on the remaining 10 ml and 2.5 ml CSF, respectively. The 10 CSF samples were successfully analyzed by TM-iFISH, and the tumor cell count range was 3-1,823 cells/7.5 ml CSF in 7 of the samples detected. There were no tumor cells detected in the remaining 3 samples. Tumor cells were revealed in 3 of the samples through the CSF cytological examinations, and albumin protein levels were indicated to be greater than the normal range (normal range, 0.15 0.45 g/l), in 9 of the samples using CSF biochemical examinations. Additionally, TM-iFISH was performed again to count the CSF malignant tumor cells in 3 of the patients following intrathecal injection of chemotherapy (methotrexate 10 mg and dexamethasone 5 mg). The results indicated that the malignant tumor cell count of 2 of the patients had decreased in comparison to the pre-treatment cell count. As it is capable of enriching and counting CSF malignant tumor cells in patients with lung cancer LM, TM-iFISH may be an effective method to diagnose lung cancer LM and to evaluate its efficacy. PMID- 26870257 TI - Nine susceptibility loci for hepatitis B virus-related hepatocellular carcinoma identified by a pilot two-stage genome-wide association study. AB - Previous studies have indicated that complex interactions among viral, environmental and genetic factors lead to hepatocellular carcinoma (HCC). To identify susceptibility alleles for hepatitis B virus (HBV)-related HCC, the present study conducted a pilot two-phase genome-wide association study (GWAS) in 660 Han Chinese individuals. In phase 1, a total of 500,447 single-nucleotide polymorphisms (SNPs) were genotyped in 50 HCC cases and 50 controls using Affymetrix GeneChip 500k Array Set. In phase 2, 1,152 SNPs were selected from phase 1 and genotyped in 282 cases and 278 controls using the Illumina GoldenGate platform. The prior probability of HCC in control subjects was assigned at 0.01, and false-positive report probability (FPRP) was utilized to evaluate the statistical significance. In phase 1, one SNP (rs2212522) showed a significant association with HCC (Pallele=5.23*10-8; ORallele=4.96; 95% CI, 2.72-9.03). In phase 2, among 27 SNPs with unadjusted Pallele<0.05, 9 SNPs were associated with HCC based on FPRP criteria (FPRP <0.20). The strongest statistical evidence for an association signal was with rs2120243 (combined ORallele=1.76; 95% CI, 1.39 2.22; P=2.00*10-6), which maps within the fourth intron of VEPH1. The second strongest statistical evidence for an association was identified for rs1350171 (combined ORallele=1.66; 95% CI, 1.33-2.07; P=6.48*10-6), which maps to the region downstream of the FZD4 gene. The other potential susceptibility genes included PCDH9, PRMT6, LHX1, KIF2B and L3MBTL4. In conclusion, this pilot two phase GWAS provides the evidence for the existence of common susceptibility loci for HCC. These genes involved various signaling pathways, including those associated with transforming growth factor beta, insulin/phosphoinositide 3 kinase, Wnt and epidermal growth factor receptor. These associations must be replicated and validated in larger studies. PMID- 26870259 TI - Effects of plant-derived anti-leukemic drugs on individualized leukemic cell population profiles in Egyptian patients. AB - Leukemias are a group of cancer types that originate from blood-forming tissues. In this disease, an abnormally large number of immature white blood cells is produced by the bone marrow. The relationship between treatments with plant derived drugs and leukemia-associated immunophenotypes (LAIPs) of clinically isolated leukemia cells has yet to be established. The aim of the present study was to develop a preliminary clinical prognostic map for commonly expressed LAIPs in patients clinically diagnosed with leukemia, as well as to assess the potential involvement of LAIPs in the response rate to 10 natural products of plant origin. An increased expression of LAIPs, including CD4, CD14, CD33 and CD34, was considered a surrogate marker of the desired response of leukemia cells to treatment with plant-derived drugs. By contrast, the increased expression of the LAIPs, MPO and DR, was associated with poor prognostic outcomes following treatment with the plant-derived drugs. The results showed that 5 of the 10 plant derived drugs tested induced the expression of several desirable LAIPs biomarkers. These findings clearly highlight the potential treatment efficacy of certain plant-derived drugs against leukemic cell types. PMID- 26870258 TI - Globular adiponectin enhances invasion in human breast cancer cells. AB - Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer. PMID- 26870260 TI - Pathological confirmation of 4 cases with isolated cortical vein thrombosis previously misdiagnosed as brain tumor. AB - Isolated cortical vein thrombosis (ICoVT) is a rare form of cerebral venous thrombosis and is easily misdiagnosed as brain tumor due to its atypical clinical presentations and radiological findings similar to brain tumors. The present study focused on 4 patients with ICoVT, 2 men and 2 women. In the 2 male patients, the onset of disease was insidious, with progressive numbness and weakness in limbs as the major symptoms. By contrast, 2 female patients suffered from acute onset of symptoms, presenting with headache and seizures. Brain computed tomography and magnetic resonance imaging showed large hemorrhagic lesions surrounded by massive edemas in the 4 patients. Brain biopsies were performed in the 4 patients due to concern for brain tumors. However, the pathological results supported the diagnosis of ICoVT, and the subsequent anticoagulant treatment administered was effective for all 4 patients. In conclusion, ICoVT can be easily misdiagnosed as brain tumor because of the atypical clinical and imaging features. The results suggested that the possibility of ICoVT always be considered in patients with neuroimaging showing cortical hemorrhagic lesions with massive edemas. PMID- 26870261 TI - Mantle cell lymphoma with multiple lymphomatous polyposis and intussusception: A case report. AB - Mantle cell lymphoma (MCL) is a rare malignant lymphoma of the gastrointestinal (GI) tract that may present as multiple lymphomatous polyposis (MLP); however, MLP with intussusception is rarely reported in MCL. In the present study, a 54 year-old male patient was diagnosed with MCL, presenting with numerous polypoid lesions of the complete GI tract combined with ileocecal intussusception. Right hemicolectomy was performed in order to prevent complicated intussusception and for tumor debulking. In addition, 6 cycles of chemotherapy were performed with the rituximab plus hyper-CVAD regimen. Subsequent to the planned chemotherapy cycles, follow-up examination demonstrated a complete response and the remission lasted for 3 years until the present time. PMID- 26870263 TI - Clinicopathological features of dermatofibrosarcoma protuberans. AB - Dermatofibrosarcoma protuberans (DFSP) is a superficial cutaneous tumor of low malignant potential characterized by a high rate of local recurrence. The histopathological appearance shows uniform spindle neoplastic cells arranged in a predominantly storiform pattern, typically with positive staining for cluster of differentiation (CD)34 and vimentin on immunohistochemistry. A minority of cases of DFSP have areas of sarcomatous transformation. Wide surgical excision is the cornerstone of treatment for DFSP. The objective of the present study was to determine the clinicopathological features of DFSP. Pathological records were searched for cases of DFSP in the database of the Department of Pathology, Faculty of Medicine Ramathibodi Hospital (Mahidol University, Bangkok, Thailand) between 1994 and 2013. The results showed 68 cases with DFSP. The mean age at diagnosis was 40 years (range, 3-86 years). Among this group of patients, 26 cases (38.2%) experienced local recurrence and 6 (8.8%) exhibited sarcomatous transformation of DFSP. The factors that predict the recurrence of DFSP are an incorrect first pathological diagnosis and an inadequate surgical margin. The factors that predict the sarcomatous transformation of DFSP are a larger tumor size and an incorrect first pathological diagnosis. In patients who have tumors with spindle cells arranged in a storiform pattern, CD34 immunohistochemical staining provides the definitive diagnosis. Exact histopathological categorization is important to select the appropriate treatment and predict the clinical outcome. PMID- 26870262 TI - Epidermal inclusion cyst of the breast: A literature review. AB - An epidermal inclusion cyst (EIC) of the breast is a rare, benign condition that may potentially be malignant. The present study conducted a systematic review of the literature in order to identify pathological hypotheses, clinical characteristics, and diagnostic and treatment options. A search for relevant studies was conducted through the Scopus, Embase and Medline databases during September 2014. The search term employed was ?epidermal inclusion cyst breast?. Studies were selected if they contained adequate information regarding symptoms at presentation, diagnostic tools, pathology, characteristics, type of procedure performed and follow-up routines. A total of 35 papers describing 91 patients affected by EIC of the breast were identified. Following this, a total of 82 patients, including an additional case supplied from the present study, were selected for further analysis. EIC of the breast typically occurs during the fifth decade of life. A palpable mass of the breast was present in 65 (79%) patients. Ultrasonographic imaging was consistently utilized as a diagnostic tool in all the cases analyzed, whereas fine-needle aspiration cytology was used in 70% of the cases and mammography in 65%. No tumor recurrence was reported at a mean follow-up time of 53 months. The present study demonstrated that elliptical excision is the preferred treatment for EIC of the breast, with pathological analysis required to exclude malignancy. PMID- 26870264 TI - Sigmoid colonic metastasis by lymphatic spread occurring with unilateral Krukenberg tumor considered to be caused by stage IA early gastric cancer: A case report. AB - Gastric cancer is one of the most common malignancies in Asia, and the second most common cause of cancer-associated mortality in Japan. Colorectal metastases originating from gastric adenocarcinoma are extremely rare. The present study reports an unusual case of lymphogenous sigmoid metastasis of gastric adenocarcinoma occurring in a 58-year-old female patient. Endoscopic and radiological findings were indicative of 0-IIc+IIa early gastric cancer, and radical distal gastrectomy with D2 lymph node dissection was performed. The pathological diagnosis was stage IA gastric adenocarcinoma (T1bN0M0), according to the Japanese classification of gastric cancer. A follow-up examination at 18 months post surgery revealed a recurrence of paraaortic lymph node metastasis, detected by abdominal computed tomography (CT) and positron emission tomography (PET)/CT. The patient received chemotherapy with S-1 and cisplatin. Subsequently, radiotherapy was administered to the paraaortic lymph nodes at levels Th11-L3. Follow-up abdominal CT and PET/CT revealed an enlarged left ovary, and abnormal uptake in the left ovary and sigmoid colon. An oophorectomy and sigmoidectomy with D3 lymph node dissection were performed. The pathological diagnosis was metastatic adenocarcinoma; this was identical to the gastric pathology in the previous pathological report. The patient continued treatment with chemotherapy. Although sigmoid colonic metastasis from gastric cancer is extremely rare, metastasis from gastric cancer must be considered during the differential diagnosis of cases involving a colorectal mass and a previous history of gastric cancer. PMID- 26870265 TI - Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the alpha7 nicotine acetylcholine receptor and phosphoinositide kinase 3-dependent pathway. AB - Cigarette smoking not only promotes lung carcinogenesis, but it has also been demonstrated to promote the progression of lung cancer. Despite nicotine being a major component of cigarette smoke, it is not carcinogenic when acting alone. Instead, it is believed to function as a tumor promoter. Due to the fatal consequences of lung cancer being primarily associated with the processes of invasion and metastasis, the present study aimed to determine the effect of nicotine on the migratory activity of lung cancer cells. The effect of nicotine on the migration of lung cancer A549 cells was evaluated by a wound healing assay. Hepatocyte growth factor (HGF) was used as a pro-migratory stimulus. During several of the experiments, specific inhibitors of alpha7-nicotine acetylcholine receptor (alpha7-nAchR), phosphoinositide kinase-3 (PI3K) and extracellular signal-related kinase (ERK)1/2 were included. The phosphorylation levels of Akt and ERK1/2 were examined using a cell-based protein phosphorylation assay. It was observed that nicotine did not induce cell migration by itself, but that it instead promoted HGF-induced cell migration. The effects of nicotine were inhibited by the pretreatment of the cells with the alpha7-nAchR inhibitor, methyllycaconitine, and the PI3K inhibitor, LY294002. The mitogen-activated protein kinase/ERK kinase kinase inhibitor exerted modest, but non-significant inhibitory activity on the effect of nicotine. Nicotine did not induce Akt phosphorylation by itself, but instead promoted the HGF-induced phosphorylation of Akt. It was also observed that nicotine had no effect on ERK1/2 phosphorylation. The results from the present study indicate that nicotine, when alone, does not have a pro-migratory function, but instead enhances responsiveness to the pro-migratory stimulus emitted by HGF. The current study provides an insight into the mechanism of tumor promotion by demonstrating that nicotine and alpha7-nAchRs act in synergy with the HGF-induced PI3K/Akt signaling pathway, increasing the sensitivity of lung cancer cells to HGF, and thereby promoting cell migration, a vital step in invasion and metastasis. PMID- 26870266 TI - Downregulation of Pygopus 2 inhibits vascular mimicry in glioma U251 cells by suppressing the canonical Wnt signaling pathway. AB - Gliomas are the most common type of malignant primary brain tumor, and the Wnt signaling pathway is associated with glioma malignancy. Pygopus protein plays an important role in developmental brain patterning, and has been identified to be a component of the Wnt signaling pathway. In the present study, the Pygopus 2 (Pygo2) protein was examined in 80 glioma tissue samples. Short hairpin (sh)RNA Pygo2 was transfected into glioma U251 cells, and the cell proliferation, colony formation and bromodeoxyuridine (BrdU) incorporation were analyzed. Western blot analysis and reverse transcription-polymerase chain reaction were used to detect the expression of Pygo2. A vascular mimicry assay was performed to examine the vascular mimicry of U251 cells. A luciferase reporter assay was used to detect the beta-catenin/Wnt system. The cyclin D1 protein was also detected using western blot analysis. The results demonstrated that inhibition of the expression of Pygo2 significantly triggered the decrease of cell proliferation, colony formation and BrdU incorporation compared with the cells treated with scramble control shRNA (shRNA-Scr). shRNA-Pygo2 transfection was found to inhibit vascular mimicry and block the Wnt signaling pathway compared to the cells transfected with shRNA-Scr. The transfection of shRNA-Pygo2 also decreased the expression of the Wnt target gene cyclin D1. In conclusion, shRNA-Pygo2 suppressed glioma cell proliferation effectively and inhibited vascular mimicry by inhibiting the expression of cyclin D1 in the canonical Wnt/beta-catenin pathway in brain glioma cells. PMID- 26870268 TI - Decitabine for the treatment of atypical chronic myeloid leukemia: A report of two cases. AB - Atypical chronic myeloid leukemia (aCML) is a hematopoietic stem/progenitor cell disorder, predominantly involving neutrophils. At present, a limited number of studies regarding the treatment of aCML have been published, and the therapies that are currently available exhibit unsatisfactory outcomes. In the present study, the cases of two aCML patients treated with decitabine (DCA) therapy who achieved remission are presented. A 48-year-old male, who presented with fatigue and a cough that had lasted two months, and a 69-year-old male who presented with dizziness, fatigue and shortness of breath with exercise, were diagnosed with aCML following bone marrow examination, flow cytometry and chromosome banding analysis. The two patients were treated with four cycles of DCA chemotherapy (20 mg/m2, days 1-5) and remission was achieved in each patient. The present study evaluated the clinical manifestations, diagnostic criteria and relevant treatment regimens of aCML, which may provide insights for the treatment of affected patients. Routine blood and bone marrow examinations were performed weekly prior to each cycle. Symptoms were relieved in both patients after the first cycle and the two patients were followed up for 3 months after completion of the final cycle. The findings of the current case report indicate that DCA may present an efficacious treatment for aCML. PMID- 26870267 TI - Baicalein inhibits the migration and invasion of colorectal cancer cells via suppression of the AKT signaling pathway. AB - The anticancer effect of baicalein has been known for a number of years. However, its anti-metastatic effect and associated mechanisms in colorectal cancer (CRC) remain unclear. The present study investigated the hypothesis that treatment with baicalein may inhibit the proliferation, motility and invasion of human CRC cell lines via regulation of the protein kinase B (AKT) signaling pathway. Baicalein was demonstrated to significantly inhibit the migration and invasion of CRC cells (P=0.01). Additionally, after treatment with baicalein for 24 h, the protein expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in CRC cells were significantly reduced in a dose-dependent manner (P=0.01). Furthermore, treatment with baicalein significantly reduced the expression levels of phosphorylated AKT (P=0.01). In conclusion, baicalein appears to inhibit CRC cell migration and invasion by reducing the expression of MMP-2 and MMP-9 via suppression of the AKT signaling pathway. Thus, baicalein is a potential novel therapeutic agent for patients with CRC. PMID- 26870269 TI - Expression and clinical significance of cyclooxygenase-2 and interleukin-32 in primary gastric B-cell lymphoma. AB - Cyclooxygenase-2 (COX-2) and interleukin-32 (IL-32) expression has been examined in various carcinomas and inflammations, and has been suggested to be significant in tumor progression and prognosis. The present study was conducted to investigate the expression of COX-2 and IL-32 in primary gastric B-cell lymphoma in order to define their clinical significance and their association with Helicobacter pylori (Hp) infection. COX-2 and IL-32 protein expression was detected in 31 primary gastric B-cell lymphoma patients and 19 chronic gastritis patients with immunohistochemistry. COX-2 and IL-32 expression was significantly higher in primary gastric lymphoma (PGL) tissues compared with gastritis tissues (51.6 vs. 21.1% for COX-2, P=0.032; and 58.1 vs. 26.3% for IL-32, P=0.029) and was significantly higher in Hp+ lymphoma tissues compared with Hp- lymphoma tissues (66.7 vs. 20% for COX-2, P=0.015; and 71.4 vs. 30% for IL-32, P=0.029). In the PGL tissues, the expression level of COX-2 was positively correlated with the expression level of IL-32, and the two were each positively correlated with Hp infection (P=0.004 for COX-2 and IL-32; P=0.01 for COX-2 and Hp infection; and P=0.003 for IL-32 and Hp infection). COX-2 expression was found to be significantly associated (P<0.05) with an aggressive tumor type, higher expression of Ki-67, frequent lymph node metastasis and advanced stage. IL-32 expression was found to be significantly correlated (P<0.05) with frequent lymph node metastasis and an advanced stage. The survival time was longer in the COX-2- and IL-32- lymphoma patients compared with the COX-2+ and IL-32+ lymphoma patients, but these differences were not statistically significant. These results suggested that Hp infection and the expression of COX-2 and IL-32 were closely linked with each other, and that the overexpression of COX-2 and IL-32 was correlated with tumor progression in primary gastric B-cell lymphoma, thus indicating potential novel therapeutic target. PMID- 26870270 TI - Upregulation of ULK1 expression in PC-3 cells following tumor protein P53 transfection by sonoporation. AB - The aim of the present study was to investigate whether ultrasound combined with microbubbles was able to enhance liposome-mediated transfection of genes into human prostate cancer cells, and to examine the association between autophagy and tumor protein P53 (P53). An MTT assay was used to evaluate cell viability, while flow cytometry and fluorescence microscopy were used to measure gene transfection efficiency. Autophagy was observed using transmission electron microscopy. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to assess the expression of autophagy-associated genes. The results of the present study revealed that cell viability was significantly reduced following successfully enhanced transfection of P53 by ultrasound combined with microbubbles. In addition, serine/threonine-protein kinase ULK1 levels were simultaneously upregulated. Castration-resistant prostate cancer is difficult to treat and is investigated in the present study. P53 has a significant role in a number of key biological functions, including DNA repair, apoptosis, cell cycle, autophagy, senescence and angiogenesis. Prior to the present study, to the best of our knowledge, increased transfection efficiency and reduced side effects have been difficult to achieve. Ultrasound is considered to be a 'gentle' technique that may be able to achieve increased transfection efficiency and reduced side effects. The results of the present study highlight a potential novel therapeutic strategy for the treatment of prostate cancer. PMID- 26870271 TI - Establishment and molecular characterization of cell lines from Japanese patients with malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is an aggressive disease that is resistant to conventional therapies. Cell lines are useful models for studying the biological characteristics of tumors; therefore, the establishment of MPM cell lines is valuable for exploring novel therapeutic strategies for MPM. In the present study, 4 MPM cell lines (YUMC8, YUMC44, YUMC63, and YUMC64) were established, which consisted of 2 epithelioid and 2 sarcomatoid mesothelioma histological subtypes, from Japanese patients with MPM. The DNA methylation status, mutations, copy number gains, protein expression of representative genes, and the sensitivity to several drugs were examined in these 4 cell lines. Methylation of P16 was demonstrated in 3/4 cell lines, in which the protein expression of p16 was lost. Methylation of RASSF1A was observed in 3/4 cell lines. Copy number gains of EGFR, HER2 or MET were not detected in the 4 cell lines. Mutations in various genes, including EGFR, KRAS, HER2, BRAF, and PIK3CA, which are frequently detected in non-small cell lung cancer, were not detected in the 4 cell lines. microRNA-34b/c is a direct transcriptional target of p53 and is often silenced in MPM by promoter methylation. In the present study, miR-34b/c was heavily methylated in 2/4 established MPM cell lines. For cell adhesion molecules, E-cadherin expression was detected in the 2 epithelioid MPM cell lines, whereas N-cadherin expression was detected in all 4 established cell lines by western blotting. Vimentin was strongly expressed in the 2 sarcomatoid MPM cell lines. None of the established MPM cell lines demonstrated significant responses to the drugs tested, including NVP-AUY922, 17-DMAG, Trichostatin A, and Vorinostat. Although novel molecular findings were not observed in the current characterization of these MPM cell lines, these lines will be useful for future extensive analyses of the biological behavior of MPM and the development of novel therapeutic strategies. PMID- 26870272 TI - Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report. AB - Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients. PMID- 26870273 TI - Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2. AB - The Warburg effect is important in tumor growth. The human M2 isoform of pyruvate kinase (PKM2) is a key enzyme that regulates aerobic glycolysis in tumor cells. Recent studies have demonstrated that PKM2 is a potential target for cancer therapy. The present study investigated the effects of pantoprazole (PPZ) treatment and PKM2 transfection on human gastric adenocarcinoma SGC-7901 cells in vitro. The present study revealed that PPZ inhibited the proliferation of tumor cells, induced apoptosis and downregulated the expression of PKM2, which contributes to the current understanding of the functional association between PPZ and PKM2. In summary, PPZ may suppress tumor growth as a PKM2 protein inhibitor. PMID- 26870274 TI - Prognostic implications of survivin and lung resistance protein in advanced non small cell lung cancer treated with platinum-based chemotherapy. AB - Platinum-based chemotherapy is the first-line treatment for non-small cell lung cancer (NSCLC), but the chemotherapy often results in the development of chemoresistance. The present study aimed to explore the prognostic implications of survivin and lung resistance protein (LRP) in advanced NSCLC treated with platinum-based chemotherapy. Tumor samples were collected from 61 hospitalized patients with stage IIIB-IV NSCLC that underwent platinum-based chemotherapy. All patient samples were collected in the Oncology Department of the Third Affiliated Hospital of Guangxi Medical University between January 2006 and January 2011. Cytoplasmic survivin and LRP expression were evaluated using immunohistochemistry. The expression of LRP and survivin reached 77% (47/61) and 76% (45/61), respectively. Positive expression of survivin was associated with a lower median progression-free survival (PFS) time (4 vs. 9 months; P=0.038) and a lower median overall survival (OS) time compared with the absence of survivin expression (9 vs. 16 months; P=0.039). Patients with LRP and survivin expression (n=41) demonstrated a median PFS time of 4 months. However, patients with either LRP or survivin expression (n=10) demonstrated a median PFS time of 8 months, which is similar to the median PFS time of the 10 patients with no expression of LRP and survivin (9 months; P=0.022). Either the expression of survivin or the combined expression of LRP and survivin is associated with a poor prognosis in advanced NSCLC treated with platinum-based chemotherapy. PMID- 26870275 TI - Expression of hepatocyte growth factor and c-Met is characteristic of alpha fetoprotein-producing colorectal adenocarcinoma: A report of three cases. AB - alpha-fetoprotein (AFP)-producing colorectal adenocarcinoma is rare and typically not well recognized. In the present study, 3 cases of AFP-producing colorectal cancer are described. All 3 of these cases demonstrated increased levels of blood AFP associated with disease progression. Only case 2 exhibited classical histological hepatoid features. Following immunohistochemical tissue staining, all 3 cases were observed to be positive for AFP expression. In addition, the expression of hepatocyte growth factor (HGF), c-Met receptor and the transcription factor c-Myc were identified to be associated with the expression of AFP. The 3 cases demonstrated resistance to multiple drugs, including epidermal growth factor receptor inhibitors, despite the presence of wild-type Kirsten rat sarcoma viral oncogene homolog (K-RAS; codons 12 and 13), neuroblastoma-RAS (codons 12 and 13) and B-Raf proto-oncogene, serine/threonine kinase (V600E). We propose that hepatoid histological features or a positive AFP finding by immunohistochemistry are sufficient for a diagnosis of AFP-producing colorectal adenocarcinoma. Furthermore, we speculates that autocrine HGF/c-Met activation may be capable of inducing the dedifferentiation of common adenocarcinoma cells, reverting them to a cancer stem cell state and producing AFP or hepatoid differentiation. Consequently, therapy targeted to the HGF/c-Met signaling pathway may potentially be effective for the treatment of AFP-producing colorectal adenocarcinoma. PMID- 26870276 TI - CCR7 as a predictive biomarker associated with computed tomography for the diagnosis of lymph node metastasis in bladder carcinoma. AB - The aim of the present study was to investigate whether the expression levels of CC-chemokine receptor 7 (CCR7) combined with computed tomography (CT) was associated with lymph node metastasis in bladder transitional cell carcinoma (BTCC). For this purpose, 115 cases of BTCC were analyzed at the Department of Urology of Xiangya Hospital, Central South University (Changsha, China). Preoperative CT scans of abdomen and pelvis, immunohistochemistry of CCR7 expression in the tumor specimens and pathological findings for lymph node metastasis were assessed. In addition, the sensitivity, specificity and accuracy of CCR7 and CT for the diagnosis of lymph node metastasis in BTCC were evaluated separately and jointly. The expression levels of CCR7 were observed to be significantly higher in BTCC than in normal controls (P<0.01). Multivariate analysis indicated that the overexpression of CCR7 was an independent predictor for lymph node metastasis in BTCC (P<0.05). The sensitivity, specificity and accuracy of CCR7 combined with CT scan for the diagnosis of lymph node metastasis in BTCC were 92.3, 83.6 and 70.0%, respectively. By contrast, the sensitivity, specificity and accuracy of CCR7 alone were 88.1, 69.9 and 76.5%, respectively, while the sensitivity, specificity and accuracy of CT alone were 52.4, 79.5 and 69.6%, respectively. The results of the present study indicated that CCR7 is an independent predictor of lymph node metastasis in BTCC. Therefore, the use of CCR7 combined with CT may improve the accuracy of the diagnosis of lymph node metastasis in BTCC. PMID- 26870277 TI - Spontaneous acute epidural hematoma developed due to skull metastasis of hepatocelluar carcinoma: A case report and review of the literature. AB - Acute epidural hematoma (AEDH) is one of the most common pathological types of head trauma, and may develop without an accidental event, although this is uncommon. The present study reports the case of a 41-year-old male patient that developed spontaneous AEDH due to skull metastasis of hepatocellular carcinoma (HCC). The man was admitted to Chonnam National University Hwasun Hospital and Medical School due to drowsiness and right-sided hemiparesis. A computed tomography scan of the head revealed the presence of a large AEDH and a lytic bone lesion in the left posterior fossa and parieto-occipital region, which exhibited heterogeneous enhancement. The perioperative findings revealed a large amount of mixed-stage epidural hematoma and a soft hemorrhagic mass that exhibited lytic change on the occipital bone. No evidence of head trauma, such as skull fracture or scalp contusion, was detected. The pathological diagnosis was hematoma with metastatic HCC. The current study reports the rare case of a patient with a metastatic tumor located in the skull that resulted in the development of spontaneous AEDH. Once a sudden and unpredicted neurological deficit occurs in a patient with HCC that is also diagnosed with skull metastasis, the possibility of spontaneous AEDH developing from the metastasis should be considered. PMID- 26870278 TI - Expression levels of HER2 and MRP1 are not prognostic factors of long-term survival in 829 patients with esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is the eighth most frequent neoplasm in China. However, the expression levels of human epidermal growth factor receptor 2 (HER2) and multidrug resistance protein 1 (MRP1) in patients with ESCC remain to be determined. In the present study, 829 ESCC cases were evaluated using immunohistochemistry. The association between the expression levels of HER2 and MRP1 and the patient's clinicopathological factors was analyzed using Fisher's exact test or chi2 test. Univariate analysis was performed via Kaplan-Meier survival curves, while the Cox proportional hazard model was used for multivariate analysis. A significant correlation was observed between the expression levels of HER2 and the patient's gender (P<0.050), tumor size (P=0.013) and venous/lymphatic invasion (P=0.039). However, no significant correlation was identified between the expression levels of MRP1 and the clinicopathological factors of the patients. In univariate analysis, gender, differentiation, depth of invasion, clinical stage, adjuvant radiotherapy or chemotherapy and lymph node metastasis were significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients with ESCC (P<0.050). The graphical representation of the Kaplan-Meier estimate curves suggested that the expression levels of HER2 or MRP1 did not exert any influence on prognosis (log-rank test, P>0.050). In multivariate analysis, tumor location, gender, clinical stage, differentiation and lymph node metastasis were identified as independent factors of prognosis in patients with ESCC (P<0.050). However, the expression levels of HER2 or MRP1 were not independently associated with PFS or OS in these patients. In conclusion, the present large-scale study demonstrates that the protein expression levels of HER2 and MRP1 does not exert any influence on the prognosis of ESCC. PMID- 26870279 TI - Hepatocyte growth factor increases the invasive potential of PC-3 human prostate cancer cells via an ERK/MAPK and Zeb-1 signaling pathway. AB - Hepatocyte growth factor (HGF) has been implicated in epithelial-mesenchymal transition (EMT) in numerous types of cancer. However, to the best of our knowledge, there has been no previous evidence that HGF has a role in prostate cancer. The present study aimed to investigate the effect of HGF on EMT and invasive potential, as well as the underlying molecular mechanisms, in a human prostate cancer cell line. Therefore, PC-3 cells were treated with various concentrations of HGF for varying durations. EMT-associated proteins, including E cadherin and vimentin, were examined by western blot analysis. The effects of HGF on cell proliferation, migration, invasion and tumorigenicity were assessed using MTT, wound-healing, Transwell and soft-agar assays. Subsequently, the role of c Met in the mediation of EMT-like changes was investigated using reverse transcription-polymerase chain reaction, western blot analysis and gene knockdown by small interfering RNA. Finally, western blot analysis was used to quantify the expression of a downstream transcription factor and extracellular signal-related kinase/mitogen activated protein kinase (ERK/MAPK) signaling pathway proteins. The results indicated that treatment with HGF induced EMT-like changes and enhanced the invasive potential of PC-3 cells. There was an increase in the expression of ERK, phosphorylated-ERK and zinc finger E-box binding homeobox-1 (Zeb-1), suggesting that EMT-like changes may be mediated through the ERK/MAPK and Zeb-1 signaling pathway. Furthermore, HGF-mediated EMT-like changes were associated with c-Met activation, and these changes were able to be blocked by c Met knockdown. The present study demonstrated that HGF-induced EMT increased the invasive potential of PC-3 human prostate cancer cells through activating the ERK/MAPK and Zeb-1 signaling pathway. PMID- 26870280 TI - Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. AB - Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential carcinogenic biomarker in certain types of cancer, such as melanoma. However, its function and clinical significance in non-small cell lung cancer (NSCLC) has not been well studied. Therefore, the present study aimed to analyze the association between ATF2/phosphorylated (p)-ATF2 expression and NSCLC malignant behavior, and discuss its clinical significance. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect the expression of ATF2 in NSCLC cell lines and fresh NSCLC tissue samples. In addition, immunohistochemistry (IHC) was performed to identify the location and expression of ATF2 and p-ATF2 (threonine 71) in paraffin-embedded sections of NSCLC and adjacent normal tissue. The results demonstrated that ATF2 was markedly overexpressed in the NSCLC cells and significantly overexpressed in the fresh NSCLC tissues compared with the control cells and samples (86 paraffin-embedded tissue sections), respectively (P<0.01). Further data demonstrated that ATF2 expression levels were significantly increased in tumor tissues compared to normal tissues and ATF2 was located in the cytoplasm and nucleus. ATF2 expression was closely associated with adverse clinical characteristics such as TNM stage (P=0.002), tumor size (P=0.018) and metastasis (P=0.027). In addition, nuclear p-ATF2 staining was positive in 65/86 samples of NSCLC. Furthermore, the Kaplan-Meier analysis indicated that patients with high levels of ATF2 and p-ATF2 expression had a significantly shorter overall survival compared with patients exhibiting a low expression (P<0.01 and P<0.05, respectively). Subsequent in vitro experiments revealed that cell growth decreased following knockdown of ATF2 expression using RNA interference, indicating that ATF2 may suppress cell proliferation. Taken together, the results of the present study demonstrated that ATF2 and p-ATF2 were significantly overexpressed in NSCLC tissues, and ATF2 and p-ATF2 overexpression predicted significantly worse outcomes for patients with NSCLC. PMID- 26870281 TI - Retroperitoneal laparoscopic management of a solitary extramedullary plasmacytoma associated with human immunodeficiency virus infection: A case report. AB - Extramedullary plasmacytoma (EMP) is a rare malignant tumor that is characterized by a malignant plasma cell neoplasm. Such neoplasms in human immunodeficiency virus (HIV)-infected patients are extremely rare. To the best of our knowledge, the present study describes the first case of a solitary adrenal EMP in a patient with HIV. A 35-year-old male who had been diagnosed with HIV 3 months previously presented with a 2-week history of intermittent right flank pain. Abdominal computed tomography revealed a soft-tissue density mass in the right adrenal gland area. The patient subsequently underwent a retroperitoneal laparoscopic adrenalectomy. Post-operative pathological diagnosis revealed a solitary EMP. Although the patient refused to undergo post-operative radiotherapy and chemotherapy, no recurrence was detected after 2 years of follow-up. The present case illustrates the fact that this rare type of solitary EMP associated with acquired immune deficiency syndrome (AIDS) can occur in the adrenal glands, and that retroperitoneal laparoscopic resection of the tumor may be a good method to manage this condition. In addition, although rare, solitary EMP should be considered in the differential diagnosis of an adrenal mass in HIV-infected patients. PMID- 26870282 TI - Fusion of platelet-derived growth factor receptor beta to CEV14 gene in chronic myelomonocytic leukemia: A case report and review of the literature. AB - Myeloid tumor possessing platelet-derived growth factor receptor beta (PDGFRbeta) gene rearrangement is a rare hematological malignancy, which presents with typical characteristics of myeloid proliferation disorders and eosinophilia. In the present study, an elderly chronic myelomonocytic leukemia patient was diagnosed with chromosome rearrangement. Fluorescence in situ hybridization (FISH) was conducted with a PDGFRbeta isolate probe, and gene translocation between PDGFRbeta on chromosome 5 and genes on the chromosomes of group D (13-15) was detected. Karyotype analysis revealed a chromosome 5 break, and PDGFRbeta thyroid hormone receptor interactor 11 (CEV14) gene fusion was confirmed via reverse transcription-polymerase chain reaction (RT-PCR), which additionally revealed the chromosome rearrangement t(5;14)(q33;q32). Due to the correlation between PDGFRbeta-CEV14 expression and effectiveness of treatment with tyrosine kinase inhibitors, this fusion gene is considered to be an oncogene. In the present study, an elderly patient was diagnosed with a myeloid tumor associated with the fusion gene PDGFRbeta-CEV14, using the methods of FISH and RT-PCR. These methods were confirmed to be of significant value in improving diagnosis, guiding treatment and increasing the cure rate of patients, due to their ability to detect multiple rearrangement genes associated with PDGFRbeta in myelodysplastic and myeloproliferative neoplasms. PMID- 26870283 TI - Photodynamic therapy with a novel porphyrin-based photosensitizer against human gastric cancer. AB - The objective of the present study was to evaluate the effects of novel porphyrin based photosensitizer meso-5-[rho-diethylene triamine pentaacetic acid- aminophenyl]-10,15,20-triphenyl-porphyrin (DTP)-mediated photodynamic therapy (PDT) on the HGC27 and SNU-1 human gastric cancer cell lines. The absorption spectrum of DTP was analyzed using a microplate spectrophotometer. The HGC27 or SNU-1 cells were incubated with DTP and exposed to illumination by a 650-nm laser. The experiments were divided into four groups: A blank control, cells treated with DTP without light, cells exposed to laser light without DTP and cells treated with a combination of DTP and light together. The phototoxicity of DTP was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell apoptosis was detected by flow cytometry and Hoechst 33342 staining. In addition, the intracellular distribution of DTP was investigated by laser scanning confocal microscopy. DTP-PDT demonstrated marked phototoxicity towards HGC27- and SNU-1 cells. The rate of cell death increased significantly in a DTP concentration-dependent and light dose-dependent manner, with maximum mortality rates of 74.14 and 67.76%, respectively. There were significant differences between the therapeutic and control groups (P<0.01). In addition, the growth of cells treated with DTP or laser light alone was not inhibited. Further evaluation revealed that, following DTP-PDT, HGC27 and SNU-1 cells demonstrated notable apoptotic changes, including condensed chromatin, fragmented nuclei and apoptotic bodies, and the percentage of apoptotic cells was significantly higher than that of the control groups (P<0.01). Furthermore, confocal laser scanning microscopy revealed that DTP localized to the lysosomes but not mitochondria in the two types of tumor cell. In conclusion, significant phototoxicity and reduced cytotoxicity in dark conditions make the novel photosensitizer DTP a promising potential PDT drug for future use in the treatment of human gastric cancer. PMID- 26870284 TI - Evolution and prognosis of breast osteosarcoma: A case report. AB - Breast osteosarcoma is a rare malignancy of unknown etiology, with no standard adjuvant treatment at present. The prognosis of the disease is poor, and it has a high propensity for recurrence and metastasis. The current report presents the case of a 52-year-old woman, in whom adenomyoepithelioma gradually developed into breast osteosarcoma following three separate surgeries. The patient survived for 41 months from the initial lesion occurrence and resection in the left breast; during this time, she underwent surgery and chemotherapy (liposomal doxorubicin and cisplatin) for the treatment of disease recurrence and lung metastasis, along with molecular-targeted therapy (sunitinib). However, the patient eventually succumbed to respiratory failure due to progressive disease. The present case underwent a clear pathological transformation process, and may provide a basis for an improved understanding of the clinical characteristics and treatment of breast osteosarcoma. PMID- 26870285 TI - Prostatic adenocarcinoma presenting with metastases to the testis and epididymis: A case report. AB - Few cases of testicular metastases from prostate carcinoma have been reported, and asymptomatic metastases of prostate carcinoma to both the testis and epididymis are extremely rare. The current study presents the case of a 69-year old male with testicular and epididymal metastases from prostate carcinoma. The patient was admitted to The First Hospital of Shijiazhuang with a 2-year history of lower urinary tract symptoms. Digital rectal examination revealed an enlarged multinodular prostate, and the serum prostate-specific antigen (PSA) level was >100 ng/ml. Magnetic resonance imaging showed prostate carcinoma with seminal vesicle involvement. A prostate biopsy showed prostate gland adenocarcinoma. The Gleason score was 3+3. The immunohistochemistry results were as follows: Prostatic acid phosphatase (+++), PSA (+++), P504s (+++), p63 (-) and cytokeratin 34betaE12 (-), with a Ki-67 of ~5%. The patient was treated with a bilateral orchiectomy. The testicular pathology showed that the right testis and epididymis were invaded with metastatic adenocarcinoma. The left testis and epididymis were normal. The patient was treated with conventional flutamide endocrine therapy. At present the patient remains in a stable condition after 24 months of follow-up. PMID- 26870286 TI - Paraganglioma of the urinary bladder with chromosome duplications detected by fluorescence in situ hybridization in urine exfoliated cells: A case report. AB - Paragangliomas of the urinary bladder are rare neoplasms derived from chromaffin tissue with a chromosomal imbalance. Their preoperative diagnosis and assessment of malignant potential remain significant challenges for urologists. The current report presents the case of a 34-year-old male who presented with a history of paroxysmal gross hematuria lasting for 7 months. Chromosome duplications were detected by fluorescence in situ hybridization (FISH) in urine exfoliated cells, and the diagnosis was confirmed by histopathology following a transurethral resection. To the best of our knowledge, this is the first reported case of urinary bladder paraganglioma in which chromosomal duplications were detected by FISH in urine exfoliated cells. This may be helpful to its differential diagnosis and malignant potential determination. PMID- 26870287 TI - Acquired amegakaryocytic thrombocytopenic purpura induced by percutaneous ethanol injection during treatment of hepatocellular carcinoma: A case report. AB - Percutaneous ethanol injection is an important localized treatment method for patients presenting with hepatocellular carcinoma (HCC). Among the advantages of percutaneous ethanol injection are its minimal invasiveness, simplicity, low cost and low risk of complications. However, the increasing popularity of percutaneous ethanol injection has resulted in serious adverse effects attributed to individual variations. The present study describes the case of a patient who exhibited acquired amegakaryocytic thrombocytopenic purpura, caused by percutaneous ethanol injection treatment for HCC. This complication was promptly identified, and platelet transfusion and injection of recombinant human interleukin-11 resulted in a rapid recovery of the patient's platelet count. Attention should be given to this rare complication in patients administered percutaneous ethanol injection treatment for HCC. PMID- 26870288 TI - Role of deregulated microRNAs in non-small cell lung cancer progression using fresh-frozen and formalin-fixed, paraffin-embedded samples. AB - Non-small cell lung cancer (NSCLC) is responsible for the highest number of cancer-associated mortalities worldwide, and the five-year survival rate is <15% following the initial diagnosis. MicroRNAs (miRNAs) serve important functions in a number of human diseases, including cancer. The present study investigated the expression status, clinical relevance and functional role of miRNA in NSCLC. miRNA expression profiling was performed in lung adenocarcinoma and adjacent unaffected lung tissues using 47 groups of fresh-frozen (FF) and 45 of formalin fixed, paraffin-embedded (FFPE) samples from 11 pulmonary bulla. miR-21, -30e, 363 and -623 were further examined for differential expression in two independent cohorts. Other miRNAs, including miR-5100 and miR-650, were upregulated, while miR-10a and -26b were downregulated in FF NSCLC tissues. The associations between these miRNAs and their clinicopathological features were also investigated. miR 363, -10a and -145 were associated with lymph node status (P=0.002, 0.005 and 0.007, respectively) and miR-650 and -145 were associated with differentiation (P=0.01 and 0.05, respectively). No associations were identified for the other miRNAs examined. In the FFPE NSCLC samples, miR-30e-5p correlated with the differentiation of the tissue (P=0.011). The present study indicates that these miRNAs may be appropriate candidates for molecular diagnostic and prognostic markers in NSCLC. PMID- 26870289 TI - Myeloid-derived suppressor cells enhance the expression of melanoma-associated antigen A4 in a Lewis lung cancer murine model. AB - The cancer-testis (CT) family of antigens are expressed in multiple types of malignant neoplasm and are silent in normal tissues, apart from the testis. Immunotherapy targeting CT antigens is a promising therapeutic strategy for treatment of solid tumors. One member of this family, melanoma-associated antigen A4 (MAGE-A4), has been demonstrated to be expressed in melanomas and lung cancer. Patients with tumors expressing the MAGE-A4 antigen exhibit specific cellular and humoral immune responses to the antigen, resulting in a favorable prognosis. Conversely, the expression of MAGE-A4 is associated with poor survival in lung cancer. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells, which are upregulated in the cancer microenvironment. Little is known regarding any potential correlation between the expression of MAGE-A4 antigens and the accumulation of MDSCs. The present study aimed to examine the association between circulating MDSC levels and MAGE-A4 expression in a mouse model of Lewis lung cancer. The expression of MAGE-A4 in tumor cells or tissues was evaluated using western blotting, while the percentage of MDSCs (CD11b+Gr-1+) in the blood was detected by flow cytometry. In addition, the suppressive capacity of MDSCs and the effectiveness of MDSC depletion were assessed in C57BL/6 tumor-bearing mice. MDSCs were demonstrated to upregulate MAGE-A4 expression via the phosphosphorylated-signal transducer and activator of transcription 3705 pathway, while depletion of MDSCs decreased the tumor growth rate, prolonged median survival and enhanced the recognition of MAGE-A4 by CD8+ T cells. These findings indicated that immunotherapeutic strategies involving induction of cytotoxic T lymphocytes that target MAGE-A4, in combination with MDSC depletion, may be an effective approach to immunotherapy for cancer types with high expression of MAGE-A4. PMID- 26870290 TI - Mangiferin inhibition of proliferation and induction of apoptosis in human prostate cancer cells is correlated with downregulation of B-cell lymphoma-2 and upregulation of microRNA-182. AB - Mangiferin, a flavonoid extracted from the mango tree, possesses anti inflammatory, antibacterial, anti-herpes simplex and antitumor activity, and is able to affect immune function. The present study investigated the anticancer effects of mangiferin treatment on PC3 human prostate cancer cells, and the potential underlying mechanisms. In the present study, an MTT assay was used to analyze the proliferation of PC3 cells. Subsequently, flow cytometry and colorimetric assay kits were utilized to measure the PC3 cell apoptotic rate. The expression levels of B-cell lymphoma-2 (Bcl-2) and microRNA-182 (miR-182) were detected using western blot analysis and quantitative reverse transcription polymerase chain reaction, respectively. Finally, miR-182 and anti-miR-182 were transfected into PC3 cells, which were used to investigate the effects of mangiferin. Mangiferin treatment reduced the proliferation of PC3 human prostate cancer cells in a concentration- and time-dependent manner. In addition, mangiferin was able to promote apoptosis and induce the caspase-3 activity of PC3 human prostate cancer cells. Mangiferin treatment was also able to significantly reduce Bcl-2 expression levels and enhance miR-182 expression in PC3 cells. Finally, it was observed that mangiferin inhibited proliferation and induced apoptosis in PC3 human prostate cancer cells, and this effect was correlated with downregulation of Bcl-2 and upregulation of miR-182. PMID- 26870291 TI - Pretreatment levels of serum osteoprotegerin and p53 protein and urine telomerase as prognostic factors affecting survival in Egyptian bladder cancer patients. AB - A non-invasive marker is required for the diagnosis and follow-up of patients with bladder cancer. The aim of the current study was to evaluate the potential prognostic significance of serum osteoprotegerin (OPG), p53 protein and urine telomerase in patients with bladder cancer. For all patients, serum levels of OPG and p53 protein were determined using enzyme-linked immunosorbent assay (ELISA), and urine telomerase was assessed using a polymerase chain reaction ELISA technique. Patients were assigned into group 1 (cystectomy and adjuvant radiotherapy) or group 2 (transurethral resection and chemoradiotherapy). The results revealed that serum OPG and p53, and urine telomerase levels were significantly higher in bladder cancer patients compared with in healthy individuals (P<0.0001). High serum OPG was associated with significantly lower overall survival and disease-free survival rates (both P=0.001), and was correlated with advanced tumor stages (P<0.0001), high tumor grades (P<0.0001) and the occurrence of disease relapse (P=0.001). Serum p53 and urine telomerase did not demonstrate prognostic significance. These findings indicate that serum OPG level may be used as a diagnostic tool and a prognostic variable for patients with muscle invasive bladder cancer. Future trials are required to elucidate its therapeutic role in such patients. PMID- 26870292 TI - Appropriate use of tumour biomarkers for treatment with innovative drugs: A retrospective study. AB - Performing randomised clinical trials to address the clinical usefulness of predictive and prognostic tumour markers is a complex process for several reasons, and observational experiences may thus play an important role. The present study performed an observational retrospective analysis in Area Vasta Romagna, Italy, collecting information on tumour marker determination in 760 consecutive patients who started a new line of anticancer therapy between January and June 2010. The determination of well-known biomarkers was requested for all gastrointestinal stromal tumour (GIST) patients (n=13) and for almost all breast cancer patients (n=369), and targeted therapies were consequently prescribed. Conversely, Kirsten rat sarcoma viral oncogene homolog (KRAS) determination in colon cancer patients (n=177) was requested in ~50% of advanced cases, while epidermal growth factor receptor (EGFR) determination was required in slightly more than 30% of the same patients. EGFR and KRAS determinations were requested in only 15% and 7.5% of non-small cell lung cancer (NSCLC) patients (n=201), respectively. There would appear to be greater appropriateness of tumour marker determination for breast cancer and GISTs than for colon cancer and NSCLC. Resources can be further optimised by standardising tumour marker determinations in terms of the timing of requests and the consequent use of the results for tailored treatment planning. PMID- 26870293 TI - Villoglandular papillary adenocarcinoma of the uterine cervix: A report of 4 cases and a review of the literature. AB - To investigate the clinicopathological features, management and prognosis of villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix, the current study presents 4 cases of VGPA of the uterine cervix. The median age of the patients was 55 years (range, 47-70 years), with all 4 patients presenting with stage Ib disease. Human papillomavirus (HPV) infection was detected in 3 patients; this was mainly HPV-16. No history of oral contraceptive use was found in these cases. While 2 of the patients underwent a radical hysterectomy with bilateral salpingo-oophorectomy plus bilateral pelvic lymphadenectomy, 1 patient underwent a radical hysterectomy with bilateral pelvic lymphadenectomy and the remaining patient received a simple total hysterectomy plus post-operative radiotherapy. Of these patients, only 1 had been correctly diagnosed pre operatively. In 2 patients, the biopsy results had been interpreted as cervical adenocarcinoma, and in the third, the biopsy result was of cervical intraepithelial neoplasia. All 4 patients presented with cervical wall invasion, including invasion of the inner two-thirds in 1 patient. No lymphovascular space invasion or lymph node metastasis was detected. The follow-up time ranged from 49 to 83 months (median, 64 months), and the patients are currently alive and well, with no evidence of recurrent disease. Taking these results as a whole, VGPA is an uncommon type of cervical adenocarcinoma, characterized by its excellent prognosis. HPV infection is associated with the molecular pathogenesis of VGPA, while oral contraceptive use can be excluded. As the disease has a low pre operative diagnostic accuracy, frequent cervical wall invasion and concomitant lesions, conservative treatment strategies should be carefully considered. PMID- 26870294 TI - DNA hypermethylation of the vimentin gene inversely correlates with vimentin expression in intestinal- and diffuse-type gastric cancer. AB - The vimentin gene is a hallmark of epithelial-to-mesenchymal transition and has been observed to be overexpressed in various types of tumor cell line and tissue. Previous studies have reported correlations between vimentin DNA methylation levels and subsequent vimentin expression levels in solid tumors, including breast and colorectal cancer; however, to the best of our knowledge, such a correlation has not been reported for gastric cancer (GC) using Lauren classification. Therefore, the present study aimed to quantify DNA methylation levels of the vimentin gene using quantitative (q) methylation-specific polymerase chain reaction (PCR) in intestinal-type GC cell lines (MKN-28, AGS and MKN-1), diffuse-type GC cell lines (SGC-7901, SNU-5 and KATO III), the GES-1 immortalized human non-neoplastic gastric epithelial cell line, as well as in tumor and paratumor normal tissue samples. Furthermore, the present study analyzed the messenger RNA expression of the vimentin gene in these cell lines and tissues by reverse transcription-qPCR. A comparison of the clinicopathological features was conducted between patients, grouped according to the Lauren classification. The present study identified that the vimentin promoter region was hypermethylated in all GC cell lines and tumor tissue samples when compared with immortalized normal gastric epithelial cells and paratumor normal tissues. In addition, vimentin promoter methylation levels were observed to be higher in intestinal-type cell lines when compared with those of diffuse type lines and tissues. Correspondingly, vimentin expression levels were lower in intestinal-type gastric cell lines compared with those of diffuse-type cell lines and tissues, and were lowest in the non-neoplastic gastric cell line and paratumor normal tissues. Patients with diffuse-type GC were on average younger (P=0.023), and exhibited higher tumor (P=0.020), node (P=0.032) and TNM classification of malignant tumor stage (P=0.039) than those with intestinal-type GC. Following treatment of AGS cells (which demonstrated the highest methylation level of the vimentin gene) with 5-aza-2'-deoxycytidine, vimentin expression was restored significantly. Thus, the present study revealed that vimentin promoter methylation levels are inversely correlated with vimentin expression levels in GC (according to Lauren classification). High levels of methylation in the vimentin gene promoter region may be involved in carcinogenesis and the development of GC, and may provide a novel molecular classification for GC. PMID- 26870295 TI - Radiation dose to the lymph drainage area in esophageal cancer with involved field irradiation. AB - The aim of this study was to quantify the radiation dose to the corresponding lymph drainage area in esophageal cancer using three-dimensional conformal radiation therapy (3D-CRT) with involvED-field IRradiation (IFI) and to analyze associated factors. A retrospective analysis oF 81 patients with esophageal cancer was conducted. According to the location of the lesions, the lymph drainage area was delineated and the dosimetric parameters were calculated. The 1 , 3-, 5- and 8-year survival rates of the patients were 67.90, 33.33, 20.99 and 11.11%, respectively. Based on the dose-volume histogram in the treatment plan, we calculated the volume percentage of the planning target volume including clinically positive lymph nodes (PTV-N) receiving radiation doses of 30, 35, 40, 45 and 50 Gy (VPTV-N30-50). The median values of VPTV-N30-50 were 73, 70, 67, 64 and 58%, respectively. The prescribed dose size exhibited no correlation with VPTV-N30-35, but did exhibit a significant correlation with VPTV-N40-50; the radiation field was not correlated with VPTV-N30-45, but exhibited a significant correlation with VPTV-N50; The length of the lesion on esophageal barium meal X ray and the PTV were significantly correlated with VPTV-N30-50. The analysis of variance revealed that the VPTV-NX value in the upper thoracic segment was higher compared with that in the middle and lower thoracic segments; VPTV-N30-35 values differed significantly according to the different locations of the lesions, whereas VPTV-N40-50 values exhibited no significant differences. The value of VPTV-NX exerted no significant effect on long-term patient survival. Therefore, the corresponding lymph drainage area of esophageal cancer IS subjected to a certain Radiation dose when patients undergo 3D-CRT with IFI, which may play a role in the prevention of regional nodal metastasis. However, this hypothesis requires confirmation by further clinical studies. PMID- 26870296 TI - Central nervous system recurrence of desmoplastic small round cell tumor following aggressive multimodal therapy: A case report. AB - Patients with desmoplastic small round cell tumors (DSRCTs) have an extremely poor outcome despite the use of aggressive therapy. The current study presents the case of 16-year-old male with metastatic DSRCT, in which multimodal therapy, including intensive chemotherapies using frequent autologous stem cell support, gross resection of primary and metastatic lesions, and whole abdominopelvic intensity-modulated radiation therapy, was administered. Subsequent to these treatments, there was no evidence of active disease. However, cerebellar and pineal body lesions, and bone metastasis to the left humerus were detected 1 year and 2 months after the initial diagnosis. Combination chemotherapy with irinotecan and temozolomide was initially effective against the central nervous system (CNS) metastatic lesions; however, the patient succumbed due to progressive CNS disease after seven courses of combination chemotherapy. Additional studies are required to accumulate information regarding CNS recurrence of DSRCT. PMID- 26870297 TI - Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells. AB - GATA5 is a transcription factor that is capable of suppressing the development of various types of human cancer. The present study investigated the expression of GATA5 and GATA4, and examined their roles in the proliferation and colony formation ability of hepatocellular carcinoma (HCC) tissues and cells. The GATA4 and GATA5 expression levels and gene promoter methylation of HCC tissue samples from 38 patients and HCC cell lines were analyzed using reverse transcription polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP), respectively. The effects of GATA4 and GATA5 overexpression on the proliferation and colony forming ability of HCC cells were also assessed using cell viability and colony formation assays. A luciferase reporter assay was utilized to investigate the transcriptional interaction of GATA4 and GATA5 with canonical Wnt signaling. The results indicated that the expression levels of GATA4 and GATA5 were lost or reduced following methylation of gene promoters in HCC tissues and cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine (5-AZA), restored GATA4 and GATA5 expression in HCC cell lines. Furthermore, methylation of the GATA5 promoter was observed to be associated with the age of patients exhibiting HCC. Restoration of GATA4 and GATA5 expression inhibited colony formation and induced apoptosis of HCC cells in vitro. The present study concluded that the expression levels of GATA4 and GATA5 were reduced in HCC tissues and cell lines. Treatment with 5-AZA restored GATA4 and GATA5 expression in HCC cell lines, suppressing tumor cell growth and colony formation, as well as inducing apoptosis. PMID- 26870298 TI - Truncated neurokinin-1 receptor is an ubiquitous antitumor target in hepatoblastoma, and its expression is independent of tumor biology and stage. AB - The substance P (SP; also known as TAC1)/neurokinin-1 receptor (NK1R; also known as TACR1) complex is a critical part in the development of cancer. Therefore, NK1R antagonists, such as the clinical drug aprepitant, are currently under investigation as future anticancer agents. In a previous study, NK1R (TACR1) was identified as a potent anticancer target in hepatoblastoma (HB). However, little is known regarding the exact distribution of this target among HB subsets and whether it correlates with clinical features and prognosis. In the present study, mRNA was isolated from 47 children with HB, and reverse transcription quantitative polymerase chain reaction was performed on the samples to analyze the expression of full-length-TACR1 (fl-TACR1) and truncated-TACR1 (tr-TACR1). These data were correlated with data obtained from 9 tumor-free controls, as well as with the presence of metastasis, PRETEXT, vascular invasion, histology, age of diagnosis, multifocality, CTNNB1 mutation, gender and overall survival. Additionally, the present study investigated a recently described 16-gene signature characterizing HB known to correlate with prognosis. Compared with tumor-free liver tissue, tumorous tissue expressed TACR1 significantly higher for the truncated version (P=0.0301), and by trend also for the full-length version. Accordingly, the expression of fl-TACR1 correlated with the expression of the truncated version (P=0.0074). Furthermore, a low expression of fl-TACR1 correlated with characteristics of the 16-gene signature known to predict prognosis (P=0.0222). However, there was no correlation between tr-TACR1 and the tumor characteristics investigated, including outcome, although a clear trend was observed for some tumor characteristics. The current results reinforced the previously described findings that in HB, tr-TACR1 is overexpressed compared with tumor-free liver tissue. Furthermore, to the best of our knowledge, the present study demonstrated for the first time that tr-TACR1 is expressed ubiquitously among the different subsets of HB. Therefore, NK1R may serve as a potent anticancer target in a large variety of patients with HB, independent of tumor biology and clinical stage. PMID- 26870299 TI - Predicting the failure of retrograde ureteral stent insertion for managing malignant ureteral obstruction in outpatients. AB - Malignant ureteral obstruction (MUO) is an unpropitious sign that is commonly observed in patients with advanced incurable cancer. The present study aimed to evaluate predictive factors for the failure of retrograde ureteral stent insertion in the management of MUO in outpatients. A total of 164 patients with MUO were retrospectively assessed in this study. Clinical factors, including age, gender, type of malignancy, level of obstruction, cause of obstruction, pre operative creatinine level, degree of hydronephrosis, condition of the contralateral ureter, prior radiotherapy, Eastern Cooperative Oncology Group performance status (ECOG PS), bladder wall invasion and technical failure, were recorded for each case. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for predicting the failure of retrograde ureteral stent insertion. In total, 38 out of 164 patients experienced bilateral obstruction, therefore, a total of 202 ureteral units were available for data analysis. The rate of insertion failure in MUO was 34.65%. Multivariate analyses identified ECOG PS, degree of hydronephrosis and bladder wall invasion as independent predictors for insertion failure. Overall, the present study found that rate of retrograde ureteral stent insertion failure is high in outpatients with MUO, and that ECOG PS, degree of hydronephrosis and bladder invasion are potential independent predictors of insertion failure. PMID- 26870300 TI - Non-invasive detection of nasopharyngeal carcinoma using saliva surface-enhanced Raman spectroscopy. AB - The present study evaluated the use of saliva surface-enhanced Raman spectroscopy (SERS) for the detection of non-invasive nasopharyngeal carcinoma (NPC). SERS measurements were taken from 62 saliva samples, of which 32 were from NPC patients and 30 from healthy volunteers. Notable biochemical Raman bands in the SERS spectra were tentatively assigned to various saliva components. The saliva SERS spectra obtained from the NPC patients and the healthy volunteers were also analyzed by multivariate statistical techniques based on principal component analysis and linear discriminant analysis (PCA-LDA). Significant differences were observed between the saliva SERS spectral intensities for NPC patients and healthy volunteers, particularly at 447, 496, 635, 729, 1134, 1270 and 1448 cm-1, which primarily contained signals associated with proteins, nucleic acids, fatty acids, glycogen and collagen. The classification results based on the PCA-LDA method provided a relatively high diagnostic sensitivity of 86.7%, specificity of 81.3% and diagnostic accuracy of 83.9% for NPC identification. The results from the present study demonstrate that saliva SERS analysis used in conjunction with PCA-LDA diagnostic algorithms possesses a promising clinical application for the non-invasive detection of NPC. PMID- 26870301 TI - Re-evaluation of various molecular targets located on CD34+CD38-Lin- leukemia stem cells and other cell subsets in pediatric acute myeloid leukemia. AB - Leukemia stem cells (LSCs) are hypothesized to be capable of driving the development of leukemia, and are responsible for disease relapse. Antibody therapy targeting cell surface antigens has significantly improved the treatment outcomes of leukemia. Therefore, it is important to identify cell surface markers that are expressed on LSCs, and that are unexpressed or expressed at reduced levels on normal hematopoietic stem cells (HSCs), in order to establish novel therapeutic targets. In the present study, the immunophenotypic characteristics of cluster of differentiation (CD)34+CD38-lineage (Lin)- stem cells were analyzed, and antigen expression levels were compared with the expression of other cell components, using multicolor flow cytometry, in 54 patients with newly diagnosed acute myeloid leukemia (AML) and 11 control patients with immune thrombocytopenia. The findings indicated that CD133 and human leukocyte antigen (HLA)-DR were expressed on normal HSCs and on AML LSCs, with no significant difference (P>0.05). By contrast, CD33, CD123 and CD44 were highly expressed on AML LSCs, and demonstrated significant differences compared with their expression on normal HSCs (CD33, 81.7 vs. 18.3%; CD123, 75.8 vs. 19.1%; CD44, 97.7 vs. 84.4%). Among the aforementioned antigens, CD33 and CD123 were promising candidates for targeted therapy for the treatment of AML. This was particularly evident for CD123 in immature AML subtype cells, which may require additional investigation within a clinical trial setting. CD44, CD133 and HLA-DR may not be suitable for leukemia targeting due to their broad and high expression levels on normal HSCs and other tissues. PMID- 26870302 TI - Refractory hypoglycemia controlled by systemic chemotherapy with advanced hepatocellular carcinoma: A case report. AB - Non-islet cell tumor hypoglycemia (NICTH) is an uncommon but serious complication of malignancy. Patients with NICTH may appear unwell due to the underlying tumor, particularly when the mechanism of hypoglycemia is extensive tumor burden in the liver. Hepatocellular carcinoma (HCC) is reported to be the second most common cause of NICTH. The therapeutic strategies used in treating NICTH involve reduction of the tumor mass or tumor load, and palliative treatment of symptoms if curative attempts fail. In the present study we report the successful control of hypoglycemia using systemic chemotherapy in an advanced HCC patient who presented with refractory NICTH. PMID- 26870303 TI - Solitary fibrous tumor of the salivary gland: A case report. AB - Solitary fibrous tumors (SFTs) are rare soft-tissue tumors of mesenchymal origin. Occasionally, these lesions have been indicated to associate with the salivary glands. Through the analysis of magnetic resonance imaging sequences, the present study reports a case of a solitary salivary gland lesion, demonstrating a well circumscribed, soft-tissue tumor with marked signal changes and homogenous enhancement. SFT should be considered as a differential diagnosis when a solid mass exhibiting hypointensity on T1-weighted images and hyperintensity on T2 weighted images has been detected in the salivary gland. Due to the potentially malignant nature of SFTs, it is necessary for radiologists to improve their understanding of such lesions. PMID- 26870304 TI - miR-128 regulates the apoptosis and proliferation of glioma cells by targeting RhoE. AB - In this study, we investigate whether miR-128 is capable of regulating the apoptosis and proliferation of human U251 glioma cells by downregulating RhoE. The expression of miR-128 was assessed by quantitative polymerase chain reaction in normal brain tissue and glioma samples. A significant downregulation of the expression of miR-128 was detected in glioma in contrast to normal brain tissue. Following the transfection of pre-miR-128 and anti-miR-128 into U251 cells, the high expression of miR-128 could inhibit proliferation and induce apoptosis in U251 cells, and those effects could be restored by miR-128 knockdown. To analyze the regulation mechanism of miR-128, TargetScan, miRanda and PicTar were used to ascertain whether RhoE was a potential target gene. Next, luciferase activity assay and western blot analysis confirmed that RhoE was a direct and specific target gene of miR-128. The advanced effects of pre-miR-128 on the apoptosis and proliferation of U251 cells were reversed by the upregulation of RhoE expression. In summary, aberrantly expressed miR-128 regulates apoptosis and proliferation in human glioma U251 cells partly by directly targeting RhoE. This finding may offer a new potential therapeutic strategy for the treatment of glioma. PMID- 26870305 TI - Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments. AB - BACKGROUND: Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between places within an environment). METHODS: Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C. RESULTS: Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together. CONCLUSIONS: Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo spatial processing in the atypical groups. PMID- 26870306 TI - An ultra-sensitive dual-mode imaging system using metal-enhanced fluorescence in solid phantoms. AB - In this study we developed a highly sensitive dual modal imaging system designed for gold nanoparticles (GNPs) conjugated to various fluorophores in solid phantoms. The system consists of fluorescence lifetime imaging microscopy (FLIM) for surface imaging, diffusion reflection (DR) for deep tissue imaging (up to 1cm), and metal enhanced fluorescence (MEF). We detected quenching in fluorescent intensity (FI) for the conjugation of gold nanospheres (GNS) as well as gold nanorods (GNRs) to Fluorescein, which has an excitation peak at a wavelength shorter than the surface plasmon resonance (SPR) of both types of GNPs, and enhanced FI in conjugation to Rhodamine B and Sulforhodamine B, both with excitation peaks in the GNPs' SPR. The enhanced FI was detected in solution as well as in solid phantoms from FLIM measurements. DR measurements detected GNR presence within the solid phantoms by recording dropped rates of light scattering using wavelengths corresponding to the GNRs' absorption. With the inclusion of MEF, this promising dual modal imaging technique enables efficient and sensitive molecular and functional imaging. PMID- 26870307 TI - Prevalence of Quinolone Resistance Genes Among Extended-Spectrum B-Lactamase Producing Escherichia coli in Mashhad, Iran. AB - BACKGROUND: Escherichia coli is an important bacterial species based on incidence and associated infection severity. Some E. coli strains produce extended-spectrum beta lactamase (ESBL) and are called ESBL-producing E. coli. These strains are resistant to most classes of cephalosporin and a number of other classes of antibiotics. Plasmids carrying qnr genes have been found to transmit quinolone resistance. OBJECTIVES: The aim of this study was to determine the frequency of qnr genes in ESBL-producing and non-ESBL-producing E. coli isolated from outpatient and hospitalized patient clinical specimens from Imam Reza hospital in Mashhad, Iran. MATERIALS AND METHODS: Two hundred E. coli strains, isolated from different clinical specimens were used. ESBL-producing E. coli were detected by determining susceptibility to ceftazidime, cefotaxime, and cefpodoxime with the phenotypic confirmatory test (PCT). PCR analysis was employed to detect the qnrA, qnrB, qnrS, bla TEM , and bla SHV genes. RESULTS: Eighty-six (43%) isolates were ciprofloxacin-resistant. The PCT identified 85 (42.5%) of 200 E. coli isolates as ESBL-producing. The bla TEM , bla SHV , qnrA, qnrB, and qnrS gene were found in 65 (76.47%), 23 (27%), 63 (31%), 34 (17%), and 14 (7%) isolates, respectively. CONCLUSIONS: The high prevalence of quinolone resistance genes, which indicates antibiotic resistance, in the Imam Reza Hospital of Mashhad is a major concern. Hence, the antibiotics prescription policy should be revised, and infection control measures should be improved. PMID- 26870308 TI - The Cytoplasmic and Periplasmic Expression Levels and Folding of Organophosphorus Hydrolase Enzyme in Escherichia coli. AB - BACKGROUND: Organophosphorus hydrolase (OPH) is a type of organophosphate degrading enzyme which is widely used in the bioremediation process. OBJECTIVES: In this study, the periplasmic and cytoplasmic productions and the activity of recombinant OPH in Escherichia coli were investigated and compared using two pET systems (pET21a and pET26b). MATERIALS AND METHODS: The sequence encoding the opd gene was synthesized and expressed in the form of inclusion body using pET21a-opd and in the periplasmic space in pET26b-opd. RESULTS: Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis showed a band of about 37 kDa with a maximum expression level at 30 degrees C from pET21a-opd.However, the obtained results of the periplasmic space extraction of OPH (pET26b-opd) showed a very weak band, while the cytoplasmic expression of OPH (pET21a-opd) produced a strong protein band. CONCLUSIONS: The activities studied by the production of PNP were determined by following the increase at 410 nm. The maximum PNP was produced at 30 degrees C with an optical density of 10.62 in the presence of cytoplasmic expression of OPH (pET21a-opd). Consequently, our results suggest cytoplasmic expression system as an appropriate candidate with a high amount of OPH in spite of inclusion body formation, which needs an additional refolding step. PMID- 26870309 TI - Production of Monoclonal Antibody Against Recombinant Polypeptide From the Erns Coding Region of the Bovine Viral Diarrhea Virus. AB - BACKGROUND: Bovine viral diarrhea (BVD) is an economically important cattle disease with a worldwide distribution. Detection and elimination of animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) is essential for the control of BVD and eradication of BVDV. There are usually no pathognomonic clinical signs of BVDV infection. Diagnostic investigations therefore rely on laboratory-based detection of the virus, or virus-induced antigens or antibodies. OBJECTIVES: Erns as an immunogenic protein of BVDV, is genetically and antigenically conserved among different isolates and therefore, is a candidate antigen for development of the enzyme linked immunosorbent assay (ELISA) for serological studies or identification of PI animals. The aim of this study was to produce a monoclonal antibody (MAb) against recombinant Erns. MATERIALS AND METHODS: For this purpose, recombinant maltose-binding protein (MBP)-Erns protein was expressed in Escherichia coli and purified using amylose resin chromatography column and used as an antigen in MAb production. Spleen cells of the immunized mice with the recombinant antigen were fused with SP2/0 myeloma cells. Next, culture supernatants of primary clones of fused cells were screened by indirect ELISA. After three rounds of cloning, the reactivity of the MAbs with recombinant and natural antigen was established by Western blotting. RESULTS: Based on our results, MAb against recombinant Erns was produced and reacted successfully with recombinant and natural antigens. CONCLUSIONS: With regards to the role of Erns in the identification of PI animals, it appears that Erns recombinant antigen and the specific monoclonal antibodies produced against it may be suitable for developing BVDV laboratory diagnostic assays. PMID- 26870310 TI - Detection of Epstein-Barr Virus DNA in Langerhans Cell Histiocytosis. AB - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare histiocytic proliferation of unknown etiology. It is characterized by granuloma-like proliferation of Langerhans-type dendritic cells and mainly affects young children. Although multiple investigators have suggested the possible role of viruses, such as Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), Herpes simplex virus (HSV) types 1 and 2, and Cytomegalovirus (CMV) in the pathogenesis of LCH, it remains, however, debated. OBJECTIVES: The EBV infection is reported to be associated with LCH. Nevertheless, no report could be found about involved Iranian children in English medical literature. In this study, we investigated the presence of EBV in Iranian children with LCH. PATIENTS AND METHODS: In this retrospective study, in which we investigated the prevalence of presence of EBV DNA in LCH, using paraffin-embedded tissue samples of 30 patients with LCH and 30 age and tissue-matched controls, who were operated for reasons other than infectious diseases (between the years 2002 and 2012), by real-time polymerase chain reaction (RT-PCR) method, in the department of pediatric pathology. No ethical issues arose in the study, because only the pathology reports were reviewed, retrospectively, and the patients were anonymous. RESULTS: There was a significant difference in prevalence of EBV presence between patients and controls. The EBV was found by RT-PCR in 19 (63.33%) out of 30 patients and only in eight (26.7%) of 30 control samples. The P = 0.004, was calculated using chi square test (OR: 4.75; 95% CI: 1.58 - 14.25). CONCLUSIONS: Our study is the first investigation performed on patients with LCH and its possible association with EBV in Iran. Considering the P = 0.004, which is statistically significant, the findings do support the hypothesis of a possible role for EBV in the pathogenesis of LCH. These results are in accordance with several previous investigations, with positive findings. PMID- 26870311 TI - Optimization of Recombinant Expression of Synthetic Bacterial Phytase in Pichia pastoris Using Response Surface Methodology. AB - BACKGROUND: Escherichia coli phytase is an acidic histidine phytase with great specific activity. Pichia pastoris is a powerful system for the heterologous expression of active and soluble proteins which can express recombinant proteins in high cell density fermenter without loss of product yield and efficiently secrete heterologous proteins into the media. Recombinant protein expression is influenced by expression conditions such as temperature, concentration of inducer, and pH. By optimization, the yield of expressed proteins can be increase. Response surface methodology (RSM) has been widely used for the optimization and studying of different parameters in biotechnological processes. OBJECTIVES: In this study, the expression of synthetic appA gene in P. pastoris was greatly improved by adjusting the expression condition. MATERIALS AND METHODS: The appA gene with 410 amino acids was synthesized by P. pastoris codon preference and cloned in expression vector pPinkalpha-HC, under the control of AOX1 promoter, and it was transformed into P. pastoris GS115 by electroporation. Recombinant phytase was expressed in buffered methanol-complex medium (BMMY) and the expression was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and enzymatic assay. To achieve the highest level of expression, methanol concentration, pH and temperature were optimized via RSM. Finally, the optimum pH and temperature for recombinant phytase activity was determined. RESULTS: Escherichia coli phytase was expressed in P. pastoris under different cultivation conditions (post-induction temperature, methanol concentration, and post-induction pH). The optimized conditions by RSM using face centered central composite design were 1% (v/v) methanol, pH = 5.8, and 24.5 degrees C. Under the optimized conditions, appA was successfully expressed in P. pastoris and the maximum phytase activity was 237.2 U/mL after 72 hours of expression. CONCLUSIONS: By optimization of recombinant phytase expression in shake flask culture, we concluded that P. pastoris was a suitable host for high level expression of phytase and it can possess high potential for industrial applications. PMID- 26870312 TI - Seroepidemiology of Rubella in Women Under 25 Years Old Attending Medical Centers in Ahvaz, Iran in 2013. AB - BACKGROUND: Rubella is a mild viral infection affecting women of reproductive age, and the fetus in early pregnancy, leading to miscarriage, stillbirth and Congenital Rubella Syndrome. OBJECTIVES: The present study aimed to assess serum level of anti-rubella antibodies in women younger than 25 years attending medical centers in Ahvaz city. PATIENTS AND METHODS: This descriptive cross-sectional study was conducted on 760 women younger than 25 years attending medical centers in Ahvaz. A sample of 3 mL of venous blood was taken from each woman and ELISA method was used to assess anti-rubella IgG levels. Antibody level more than 11 IU/mL was considered safe. Data was analyzed by SPSS software using Chi-square, ANOVA and Pearson Correlation tests. RESULTS: Of total samples, 683 women (88.9%) had immunity against rubella, 80 (10.4%) no immunity and 5 (0.7%) intermediate levels of antibody. Immunity to rubella increased significantly with aging (P = 0.001) and a significant association was found between age and antibody titer (P = 0.001, r = 0.261). CONCLUSIONS: More than 95% of 15 to 25 year-old women (main reproductive age in Iran) are within acceptable immunity range. Level of immunity to rubella in women of reproductive age in this region appears satisfactory. PMID- 26870313 TI - Assay of Blood and Synovial Fluid of Patients With Rheumatoid Arthritis for Staphylococcus aureus Enterotoxin D: Absence of Bacteria But Presence of Its Toxin. AB - BACKGROUND: Rheumatoid arthritis (RA) is the most common chronic inflammatory disease. The staphylococcal superantigens are considered as the causative agent of RA disease. OBJECTIVES: This study aimed to assess the presence of staphylococcal enterotoxin D in synovial fluid and blood of patients with RA. PATIENTS AND METHODS: A total of 120 blood and SF samples of patients with RA were studied. Bacterial culture, primer pairs design, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) methods have been used to assess of the staphylococcal enterotoxin D. The data were analyzed through descriptive statistics. RESULTS: During this study and after sequential subcultures, only 5 bacterial strains were isolated. The results of PCR showed the presence of staphylococcal enterotoxin D gene in almost 50% of SF and also in 48.4% of blood samples of patients with RA. Similarly, the ELISA method detected staphylococcal enterotoxin D in 36.16% of SF and in 33.33% of blood of patients with RA. CONCLUSIONS: The result of this study showed that a high percentage of patients with RA have shown staphylococcal enterotoxin D (superantigen D) or entD gene in SF and in blood. However, the origin of this superantigen was not clarified and no Staphylococcus aureus enterotoxin D producer was isolated. This finding indicates other role of this superantigen besides its intoxication. Therefore, staphylococcal enterotoxin D as a biomarker may provide a good model for the diagnosis and treatment of patients with RA. PMID- 26870314 TI - Mannose-Binding Lectin Serum Levels in Patients With Candiduria. AB - BACKGROUND: Candida species are normal mycoflora of human body which are capable to cause urinary tract infection (UTI). Mannose-binding lectin (MBL) is a kind of innate immune system and decreasing plasma levels of MBL may disrupt the natural immune response and increase susceptibility to infections. OBJECTIVES: The aim of the present study was to assess MBL in the serum of patients with candiduria and compare them with control. PATIENTS AND METHODS: The blood and urine samples were collected from 335 patients (hospitalized in Golestan hospital, Ahvaz) using standard methods and the growing colonies on CHROMagar were identified using routine diagnostic tests. MBL activity in the serum of 45 patients with candiduria and 45 controls was measured using Eastbiopharm enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: In this study, 45 (13.4 %) urine samples were positive for Candida species (17 males and 28 females). The most common isolated yeast was Candida albicans (34%), followed by C. glabrata (32.1%), C. tropicalis (9.4%), other Candida species (22.6%), and Rhodotorula species (1.9%). The mean serum levels of MBL were 0.85 +/- 0.01 ng/mL and 1.02 +/ 0.03 ng/mL among candiduric patients and controls, respectively, and there was no significant difference between the two groups (P = 0.6). CONCLUSIONS: Our results showed that there was no significant relationship between MBL serum levels and candiduria. PMID- 26870316 TI - Evaluating sex as a biological variable in preclinical research: the devil in the details. AB - Translating policy into action is a complex task, with much debate surrounding the process whereby US and Canadian health funding agencies intend to integrate sex and gender science as an integral component of methodological rigor and reporting in health research. Effective January 25, 2016, the US National Institutes of Health implemented a policy that expects scientists to account for the possible role of sex as a biological variable (SABV) in vertebrate animal and human studies. Applicants for NIH-funded research and career development awards will be asked to explain how they plan to factor consideration of SABV into their research design, analysis, and reporting; strong justification will be required for proposing single-sex studies. The Canadian Institutes of Health Research is revising their peer review accreditation process to ensure that peer reviewers are skilled in applying a critical lens to protocols that should be incorporating sex and gender science. The current paper outlines the components that peer reviewers in North America will be asked to assess when considering whether SABV is appropriately integrated into research designs, analyses, and reporting. Consensus argues against narrowly defining rules of engagement in applying SABV, with criteria provided for reviewers as guidance only. Scores will not be given for each criterion; applications will be judged on the overall merit of scientific innovation, rigor, reproducibility, and potential impact. PMID- 26870315 TI - Y-chromosome phylogeographic analysis of the Greek-Cypriot population reveals elements consistent with Neolithic and Bronze Age settlements. AB - BACKGROUND: The archeological record indicates that the permanent settlement of Cyprus began with pioneering agriculturalists circa 11,000 years before present, (ca. 11,000 y BP). Subsequent colonization events followed, some recognized regionally. Here, we assess the Y-chromosome structure of Cyprus in context to regional populations and correlate it to phases of prehistoric colonization. RESULTS: Analysis of haplotypes from 574 samples showed that island-wide substructure was barely significant in a spatial analysis of molecular variance (SAMOVA). However, analyses of molecular variance (AMOVA) of haplogroups using 92 binary markers genotyped in 629 Cypriots revealed that the proportion of variance among the districts was irregularly distributed. Principal component analysis (PCA) revealed potential genetic associations of Greek-Cypriots with neighbor populations. Contrasting haplogroups in the PCA were used as surrogates of parental populations. Admixture analyses suggested that the majority of G2a-P15 and R1b-M269 components were contributed by Anatolia and Levant sources, respectively, while Greece Balkans supplied the majority of E-V13 and J2a-M67. Haplotype-based expansion times were at historical levels suggestive of recent demography. CONCLUSIONS: Analyses of Cypriot haplogroup data are consistent with two stages of prehistoric settlement. E-V13 and E-M34 are widespread, and PCA suggests sourcing them to the Balkans and Levant/Anatolia, respectively. The persistent pre-Greek component is represented by elements of G2-U5(xL30) haplogroups: U5*, PF3147, and L293. J2b-M205 may contribute also to the pre-Greek strata. The majority of R1b-Z2105 lineages occur in both the westernmost and easternmost districts. Distinctively, sub-haplogroup R1b- M589 occurs only in the east. The absence of R1b- M589 lineages in Crete and the Balkans and the presence in Asia Minor are compatible with Late Bronze Age influences from Anatolia rather than from Mycenaean Greeks. PMID- 26870317 TI - YeATS - a tool suite for analyzing RNA-seq derived transcriptome identifies a highly transcribed putative extensin in heartwood/sapwood transition zone in black walnut. AB - The transcriptome provides a functional footprint of the genome by enumerating the molecular components of cells and tissues. The field of transcript discovery has been revolutionized through high-throughput mRNA sequencing (RNA-seq). Here, we present a methodology that replicates and improves existing methodologies, and implements a workflow for error estimation and correction followed by genome annotation and transcript abundance estimation for RNA-seq derived transcriptome sequences (YeATS - Yet Another Tool Suite for analyzing RNA-seq derived transcriptome). A unique feature of YeATS is the upfront determination of the errors in the sequencing or transcript assembly process by analyzing open reading frames of transcripts. YeATS identifies transcripts that have not been merged, result in broken open reading frames or contain long repeats as erroneous transcripts. We present the YeATS workflow using a representative sample of the transcriptome from the tissue at the heartwood/sapwood transition zone in black walnut. A novel feature of the transcriptome that emerged from our analysis was the identification of a highly abundant transcript that had no known homologous genes (GenBank accession: KT023102). The amino acid composition of the longest open reading frame of this gene classifies this as a putative extensin. Also, we corroborated the transcriptional abundance of proline-rich proteins, dehydrins, senescence-associated proteins, and the DNAJ family of chaperone proteins. Thus, YeATS presents a workflow for analyzing RNA-seq data with several innovative features that differentiate it from existing software. PMID- 26870318 TI - Double-Blinding and Bias in Medication and Cognitive-Behavioral Therapy Trials for Major Depressive Disorder. AB - While double-blinding is a crucial aspect of study design in an interventional clinical trial of medication for a disorder with subjective endpoints such as major depressive disorder, psychotherapy clinical trials, particularly cognitive behavioral therapy trials, cannot be double-blinded. This paper highlights the evidence-based medicine problem of double-blinding in the outcome research of a psychotherapy and opines that psychotherapy clinical trials should be called, "partially-controlled clinical data" because they are not double-blinded. The implications for practice are, 1. For practitioners to be clear with patients the level of rigor to which interventions have been studied, 2. For authors of psychotherapy outcome studies to be clear that the problem in the inability to blind a psychotherapy trial severely restricts the validity of any conclusions that can be drawn, and 3. To petition National Health Insurance plans to use caution in approving interventions studied without double-blinded confirmatory trials as they may lead patients to avoid other treatments shown to be effective in double-blinded trials. PMID- 26870319 TI - Predictors of psychiatric rehospitalization among elderly patients. AB - The population of Hong Kong and the proportion of elderly people have been increasing rapidly. The aim of this retrospective cohort study is to determine predictive factors for psychiatric rehospitalization within 2 years among elderly patients who were discharged from psychiatric wards, in attempt to reduce their rehospitalization rate and to reintegrate them into the community. Patients aged 65 and over, who were discharged from psychiatric wards of Pamela Youde Nethersole Eastern Hospital from 1 March 2010 to 29 February 2012, were identified. Rehospitalization within 2 years after discharge was the primary outcome measure, and the time to rehospitalization was measured as the secondary outcome. Patients were subgrouped into readmitted and non-readmitted groups. Logistic regression and Cox regression analyses were applied to the potential predictive factors with odds ratios and hazard ratios obtained, respectively, for the significant findings. Kaplan-Meier survival curves were plotted for graphical representation of the study results in survival analysis. 368 individuals satisfying the study criteria were identified. The same four factors were shown to be significantly associated with rehospitalization in both multiple logistic regression and Cox regression survival analysis. Referral to other psychiatric disciplines upon discharge (p< 0.001, OR=0.325, HR=0.405) was associated with a lower rehospitalization risk and correlated to a longer time to rehospitalization. History of suicidal behaviors (p< 0.001, OR=4.906, HR=3.161), history of violent behaviors (p< 0.001, OR=5.443, HR=3.935) and greater number of previous psychiatric admissions (p< 0.001, OR=1.250, HR=1.121) were associated with a higher rehospitalization risk and predicted earlier rehospitalization. The rehospitalization rate of elderly patients was 5.2% at 1 month, 9.5% at 3 months, 15.0% at 6 months, 17.1% at 1 year, 18.8% at 1.5 year and 20.9% at 2 years. PMID- 26870320 TI - A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions. AB - The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity. Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium. PMID- 26870321 TI - Optical characterization of epidermal cells and their relationship to DNA recovery from touch samples. AB - The goal of this study was to investigate the relative contributions of different cellular and genetic components to biological samples created by touch or contact with a surface - one of the most challenging forms of forensic evidence. Touch samples were generated by having individuals hold an object for five minutes and analyzed for quantity of intact epidermal cells, extracellular DNA, and DNA from pelleted cell material after elution from the collection swab. Comparisons were made between samples where individuals had washed their hands immediately prior to handling and those where hand washing was not controlled. The vast majority (84-100%) of DNA detected in these touch samples was extracellular and was uncorrelated to the number of epidermal cells detected. Although little to no extracellular or cell pellet-associated DNA was detected when individuals washed their hands prior to substrate handling, we found that a significant number of epidermal cells (between ~5x10 (3) and ~1x10 (5)) could still be recovered from these samples, suggesting that other types of biological information may be present even when no amplifiable nuclear DNA is present. These results help to elucidate the biological context for touch samples and characterize factors that may contribute to patterns of transfer and persistence of genetic material in forensic evidence. PMID- 26870322 TI - Measuring the primary cilium length: improved method for unbiased high-throughput analysis. AB - BACKGROUND: Primary cilia are cellular protrusions involved in mechanic and chemical sensing on almost all cells of our body. Important signaling pathways, including Hedgehog, TGFbeta, and Ca(2+), are linked to cilia and/or cilia function. Cilia can vary in length, which has functional implications. To measure these lengths correctly, a standardized method with high reliability and throughput is required. To date, methods for length measurements in cultured cells after fluorescent staining for ciliary components are error prone with a possible human selection bias, primarily caused by the orientation of cilia with respect of the imaging plane. In tissue sections, accurate measurements become an even larger challenge due to additional random sectioning plane. Cilia can be reconstructed in 3D and measured one by one, but this is a labor-intensive procedure. Therefore, we developed a new, high-throughput method with less selection bias. RESULTS: To identify the optimal type of measurement of straight and relatively short cilia, three methods were compared. The first method is based on maximum intensity projection (MIP), the second method is based on the Pythagorean theorem (PyT), and the third is based on 3D alternative angled slicing (DAAS). We investigated whether cilia visible in the plane of focus ('flat cilia'), and the ones that are angled with respect to the plane of focus are represented differently among the various methods. To test the agreement between the methods, intraclass correlations are calculated. To measure flat cilia, MIP and DAAS provided representative results, with the MIP method allowing for higher throughput. However, when measuring the angled cilia with MIP, the actual cilium length is overtly underestimated. DAAS and PyT are exchangeable methods for length measurements of the angled cilia, while PyT exhibits higher throughput and is therefore the preferred method for measuring the length of an angled cilium. CONCLUSION: PyT is a universal measuring method to measure straight cilia, without selection bias. MIP provides similar results for flat cilia, but underestimates the length of angled cilia. In addition, PyT facilitates high-throughput length measurements. Manual tracking or reconstruction will be the method of choice to measure irregularly shaped cilia. PMID- 26870323 TI - Colib'read on galaxy: a tools suite dedicated to biological information extraction from raw NGS reads. AB - BACKGROUND: With next-generation sequencing (NGS) technologies, the life sciences face a deluge of raw data. Classical analysis processes for such data often begin with an assembly step, needing large amounts of computing resources, and potentially removing or modifying parts of the biological information contained in the data. Our approach proposes to focus directly on biological questions, by considering raw unassembled NGS data, through a suite of six command-line tools. FINDINGS: Dedicated to 'whole-genome assembly-free' treatments, the Colib'read tools suite uses optimized algorithms for various analyses of NGS datasets, such as variant calling or read set comparisons. Based on the use of a de Bruijn graph and bloom filter, such analyses can be performed in a few hours, using small amounts of memory. Applications using real data demonstrate the good accuracy of these tools compared to classical approaches. To facilitate data analysis and tools dissemination, we developed Galaxy tools and tool shed repositories. CONCLUSIONS: With the Colib'read Galaxy tools suite, we enable a broad range of life scientists to analyze raw NGS data. More importantly, our approach allows the maximum biological information to be retained in the data, and uses a very low memory footprint. PMID- 26870324 TI - Colorectal cancer survival in Jamaica. AB - OBJECTIVE: To determine the intermediate and long-term survival of patients diagnosed with colorectal cancer (CRC) and to determine factors that affect survival. METHOD: Patients were identified from a prospectively maintained colonoscopy database. All patients who underwent colonoscopy during the period January 2008 to December 2012 and had histologically confirmed invasive carcinoma were included. These patients were contacted at the end of 2013 to determine their survival status. In addition to demographics, variables analyzed included presenting complaint and tumor site and stage at presentation. RESULTS: Of 1757 patients being subjected to colonoscopy, 118 had endoscopic and histologic documentation of invasive CRC. Of these the survival status of 102 was determined as of December 2013 and they formed the basis of our study. The mean age of the group was 62 years with approximately 20% of the group being age 50 years or younger. Females (54%) slightly outnumbered males. Anemia or overt rectal bleeding was a dominant indication (44%) and 65% of the tumours were left sided. There were 58 (57%) deaths and the median overall survival time was two years post diagnosis. Log rank tests for equality of survivorship looking at age, gender, tumor site and presentation revealed that only presenting complaint was a predictor of survivorship (p < 0.001). Patients presenting with bleeding or anemia have the best survival. CONCLUSIONS: Long-term survival from colorectal cancer remains poor with only about 33% of patients being alive five years after their diagnosis. PMID- 26870325 TI - Mixture models detect large effect QTL better than GBLUP and result in more accurate and persistent predictions. AB - BACKGROUND: Accurate evaluation of SNP effects is important for genome wide association studies and for genomic prediction. The genetic architecture of quantitative traits differs widely, with some traits exhibiting few if any quantitative trait loci (QTL) with large effects, while other traits have one or several easily detectable QTL with large effects. METHODS: Body weight in broilers and egg weight in layers are two examples of traits that have QTL of large effect. A commonly used method for genome wide association studies is to fit a mixture model such as BayesB that assumes some known proportion of SNP effects are zero. In contrast, the most commonly used method for genomic prediction is known as GBLUP, which involves fitting an animal model to phenotypic data with the variance-covariance or genomic relationship matrix among the animals being determined by genome wide SNP genotypes. Genotypes at each SNP are typically weighted equally in determining the genomic relationship matrix for GBLUP. We used the equivalent marker effects model formulation of GBLUP for this study. We compare these two classes of models using egg weight data collected over 8 generations from 2,324 animals genotyped with a 42 K SNP panel. RESULTS: Using data from the first 7 generations, both BayesB and GBLUP found the largest QTL in a similar well-recognized QTL region, but this QTL was estimated to account for 24 % of genetic variation with BayesB and less than 1 % with GBLUP. When predicting phenotypes in generation 8 BayesB accounted for 36 % of the phenotypic variation and GBLUP for 25 %. When using only data from any one generation, the same QTL was identified with BayesB in all but one generation but never with GBLUP. Predictions of phenotypes in generations 2 to 7 based on only 295 animals from generation 1 accounted for 10 % phenotypic variation with BayesB but only 6 % with GBLUP. Predicting phenotype using only the marker effects in the 1 Mb region that accounted for the largest effect on egg weight from generation 1 data alone accounted for almost 8 % variation using BayesB but had no predictive power with GBLUP. CONCLUSIONS: In conclusion, In the presence of large effect QTL, BayesB did a better job of QTL detection and its genomic predictions were more accurate and persistent than those from GBLUP. PMID- 26870326 TI - Efficacy of traditional Chinese medicine in treating cancer. AB - The morbidity associated with cancer has rapidly increased in recent years, and in the previous 5 years has had a tendency to be the leading cause of fatality compared with cardiovascular disease. Therefore, effective measures are required with an aim to reduce the incidence. Based on the results of clinical investigation, a multidisciplinary treatment strategy for cancer, which includes radiotherapy, chemotherapy, surgery, targeted therapy and immunotherapy, are prominently used in clinical practice. However, the therapies are insufficient due to multidrug resistance, adverse effects and the presence of the root of the cancer. Therefore, there is a necessity to develop more effective or adjunctive therapies for cancer prevention and treatment. Cancer is now widely recognized as a systemic humoral disease. Similarly, the function of herbal drugs is to modulate the whole body system in a more holistic way. Recently, herbal drugs have been applied to one of the efficient approaches for cancer therapy. Furthermore, there is evidence that various herbal medicines have been proven to be useful and effective in sensitizing the conventional agents against the various factors at the cellular and molecular levels that are associated with the occurrence of cancer and in prolonging survival time, alleviating side effects of chemotherapy and radiotherapy and improving the quality of life in cancer patients. PMID- 26870328 TI - Substance-P in symptomatic mediopatellar plica as a predictor of patellofemoral pain. AB - The present study aimed to investigate the expression of a neuropeptide of symptomatic mediopatellar plica (MP) to prove that there was a significant correlation between the expression of substance-P (SP) in MP and patellofemoral pain. The specimens of synovial plica were obtained by knee arthroscopy. Semi quantitative analysis was used to investigate the expression of SP, and compared the innervation density of SP among the three groups: Blank control (asymptomatic plica), positive control (symptomatic plica with other injuries) and experimental (symptomatic plica without other injuries) groups by the paired t-test, one-way analysis of variance and Student-Newman-Keuls test in 60 patients. The expression levels of SP nerve fibers in the superior plica were 24.60+/-26.17, 117.36+/ 73.62 and 59.06+/-44.06 in the blank control, positive control and experimental groups, respectively. The density of nerve fibers in medial plica was 23.23+/ 18.41 in the blank control group, 268.00+/-71.60 in the positive control group and 255.44+/-87.91 in the experimental group. The density of nerve fibers of MP was higher compared to that of the superior plica. The density was highest in the positive control group, and lowest in the blank control group in MP. There was a close correlation between the density of SP expression and the degree of patellofemoral pain. The SP expression intensity has an important role in the incidence of patellofemoral pain and is responsible for the pathogenesis of symptomatic MP. PMID- 26870327 TI - Crimean-Congo hemorrhagic fever: Risk factors and control measures for the infection abatement. AB - Crimean-Congo hemorrhagic fever (CCHF) is a vector-borne viral disease, widely distributed in different regions of the world. The fever is caused by the CCHF virus (CCHFV), which belongs to the Nairovirus genus and Bunyaviridae family. The virus is clustered in seven genotypes, which are Africa-1, Africa-2, Africa-3, Europe-1, Europe-2, Asia-1 and Asia-2. The virus is highly pathogenic in nature, easily transmissible and has a high case fatality rate of 10-40%. The reservoir and vector of CCHFV are the ticks of the Hyalomma genus. Therefore, the circulation of this virus depends upon the distribution of the ticks. The virus can be transmitted from tick to animal, animal to human and human to human. The major symptoms include headache, high fever, abdominal pain, myalgia, hypotension and flushed face. As the disease progresses, severe symptoms start appearing, which include petechiae, ecchymosis, epistaxis, bleeding gums and emesis. Enzyme linked immunosorbent assay, quantitative polymerase chain reaction, antigen detection, serum neutralization and isolation of the virus by cell culture are the diagnostic techniques used for this viral infection. There is no specific antiviral therapy available thus far. However, ribavirin has been approved by the World Health Organization for the treatment of CCHFV infection. Awareness campaigns regarding the risk factors and control measures can aid in reducing the spread of this disease to a greater extent, particularly in developing countries. PMID- 26870329 TI - Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4. AB - The antigen-presenting capacity of specific cells and tumor immunogenicity involved in innate cellular immunity are important for initiating an antitumor response to advanced neuroblastoma. The present study was performed to establish a method of producing antigen-presenting cells that induced an immune response to murine neuroblastoma cells through culture with neuroblastoma cells that had undergone immunogenic cell death. Immunogenic death of neuro-2a murine neuroblastoma cells was induced by exposure to doxorubicin. Mouse bone marrow cells were cultured in medium containing granulocyte-macrophage colony stimulating factor, followed by the addition of doxorubicin-treated neuro-2a cells to the culture with or without lipopolysaccharide (LPS) and/or interleukin 4. Subsequently, cluster of differentiation (CD) 8alpha+ lymphocytes were co cultured with neuro-2a cells and the adherent bone marrow cells obtained by the above procedure to evaluate CD8alpha+ lymphocyte proliferation and interferon gamma production. Furthermore, the surface antigen profile of adherent bone marrow cells was analyzed by flow cytometry. When adherent bone marrow cells were treated with LPS and/or interleukin-4, followed by co-culture with CD8alpha+ lymphocytes and neuro-2a cells, interferon-gamma production by the CD8alpha+ cells increased in response to anti-CD3/CD28 antibody stimulation. CD11c major histocompatibility complex II (MHC II) double-positive cells were increased among adherent cells derived from cultured bone marrow cells. These cells were positive for DEC-205, but not CD8alpha. These findings suggest that co-culture of bone marrow-derived cells with tumor cells (that have undergone immunogenic death by exposure to doxorubicin) plus stimulation by LPS and interleukin-4 induces antigen-presenting cells that can evoke an immune response to neuroblastoma. Bone marrow-derived DEC-205+ CD11c+ MHC II+ dendritic cells are key antigen-presenting cells in the induction of an immune response following phagocytosis of doxorubicin-treated neuroblastoma cells. PMID- 26870330 TI - Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats. AB - The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer. PMID- 26870331 TI - Comparison of the influence on renal function between cefepime and cefpirome. AB - Although known for their broad spectrum and curative efficacy on drug-resistant pathogens and as nephrotoxicity-free, impairments were observed on renal function during clinical treatment of the two most commonly used fourth-generation cephalosporins: Cefpirome and cefepime. The present study aimed to further explore the exact influences of them on renal function. In vitro, the cell viability of renal cells cultured in drug-combined medium was tested for six dilutions. In vivo, a clinical cohort study was carried out to detect the influence of cefpirome and cefepime on the serum creatinine (SCr) level of patients. Cefpirome had an inhibition rate with half maximal inhibitory concentration (IC50) of 143.5 umol/l on renal mesangial cells, which was greater compared to the IC50 of 7.702 umol/l for cefepime. The clinical cohort study data revealed that cefpirome treatment could lead to a greater increase of the average SCr level compared to cefepime on days 3 and 7 during therapy, and in addition, a greater incidence of SCr >445 umol/l, an indicator of clinical renal failure. Furthermore, patients with an average age >65 years were observed as more susceptible to an SCr rise caused by either cefpirome or cefepime, with a larger augment in the average SCr, as well as a higher incidence of SCr >445 umol/l compared to patients aged <65 years. In conclusion, cefpirome may have more potential to cause renal impairment compared to cefepime, therefore, more caution and comprehensive analysis of patient conditions is required during the clinical choice of fourth-generation cephalosporins. PMID- 26870333 TI - Mechanical characteristics of the pulmonary artery in beagle dogs with hepatopulmonary syndrome and portopulmonary hypertension. AB - The continuous changes in pulmonary hemodynamic properties in hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) have not been fully characterized in large animal models of HPS and PoPH. Beagle dog models of HPS and PoPH were induced by chronic common bile duct ligation and Sephadex microspheres, respectively. The model was validated by catheter examination and pathological analyses, and the hemodynamic characteristics of the models were observed. The results revealed that the cross-sectional area of the blood vessel was significantly increased in HPS models, but it was significantly decreased in the PoPH models. Furthermore, the resistance of pulmonary circulation was elevated in models of HPS, but it was decreased in models of PoPH. The present findings renew the traditional view that pulmonary hypertension is due to the enhanced peripheral resistance. PMID- 26870332 TI - Comparison of the effects of melatonin and genistein on radiation-induced nephrotoxicity: Results of an experimental study. AB - The aim of the present study was to compare the effects of melatonin and genistein on radiation-induced nephrotoxicity (RIN). A total of 70 Swiss Albino mice were divided into 7 groups. Five control groups were defined, which were sham irradiation (C, G1), radiation therapy only (RT, G2), melatonin (M, G3), genistein (G, G4) and polyethylene glycol-400 (G5), respectively. The co treatment groups were the RT plus melatonin (RT+M, G6) and RT plus genistein (RT+G, G7) groups. Irradiation was applied using a cobalt-60 teletherapy machine (80-cm fixed source-to-surface distance, 2.5-cm depth). Melatonin was administered (100 mg/kg, intraperitoneal injection) 30 min before the single dose of irradiation, whereas genistein was administered (200 mg/kg, subcutaneous injection) 1 day before the single dose of irradiation. All the mice were sacrificed 6 months after irradiation. As an end point, the extent of renal tubular atrophy for each mouse was quantified with image analysis of histological sections of the kidney. Tissue malondialdehyde (MDA) levels were also measured in each animal. In the histopathological examination of the mouse kidneys, there was a statistically significant reduction (P<0.05) in the presence of tubular atrophy between the RT+M and RT+G groups and the RT group. There was a statistically significant increase in MDA levels in the irradiated versus sham groups (RT vs. C; P<0.05); however, MDA levels were significantly decreased by co-treatment with melatonin or genistein vs. RT alone (RT+M and RT+G vs. RT; P<0.05). In conclusion, the present experimental study showed that melatonin and genistein supplementation prior to irradiation-protected mice against RIN, which may have therapeutic implications for radiation-induced injuries. PMID- 26870334 TI - Professional oral health care reduces the duration of hospital stay in patients undergoing orthognathic surgery. AB - The present study reviewed the records of 58 patients who underwent orthognathic surgery [sagittal split ramus osteotomy (SSRO), Le Fort I osteotomy, genioplasty, anterior maxillary alveolar osteotomy] between 2010 and 2015. To investigate the influence of preoperative oral health care on postoperative inflammation, infection and length of hospital stay in those patients, white blood cell (WBC) count and C-reactive protein (CRP) levels were compared between patients who received and did not receive preoperative oral care. The mean CRP level throughout the postoperative term was lower in the oral care group as compared to the non-oral care group. By contrast, the oral care group had a lower occurrence of postoperative infectious complications (surgical site infection, anastomotic leak) (13.6 vs. 20.8%) and a shorter average length of hospital stay (16.2+/-3.8 vs. 21.2+/-7.4 days). These results suggest that preoperative professional oral health care decreases the duration of hospital stay following orthognathic surgery by inhibiting inflammation and infectious complications during the postoperative stage. PMID- 26870335 TI - Effect of interleukin-2 treatment combined with magnetic fluid hyperthermia on Lewis lung cancer-bearing mice. AB - The present study aimed to investigate the therapeutic effect of interleukin-2 (IL-2) treatment combined with magnetic fluid hyperthermia (MFH) on Lewis lung cancer-bearing mice. Magnetic fluids were prepared in vitro and directly injected into the tumors in the mice, which were subjected to an alternating magnetic field. The temperature in the tumor reached 43 degrees C and was maintained by controlling the strength of magnetic field for 30 min. Twenty-four hours later, IL-2 was injected directly into the tumors. Mice were divided into four groups: Group I (control), II (MFH), III (IL-2) and IV (IL-2+MFH). The tumor grew gradually in groups II and IV (both P<0.05) compared to the control group. Histological analysis showed that the tumor cells underwent apoptosis and necrosis. Immunohistochemistry results demonstrated that heat-shock protein 70 and cluster of differentiation (CD) 8-positive and CD4-positive T cells were strongly expressed following hypothermia. Therefore, the present study provided evidence that IL-2 treatment combined with MFH improves the therapeutic effect on lung cancer-bearing mice. PMID- 26870336 TI - CXC chemokine receptor 7 expression in cervical intraepithelial neoplasia. AB - Cervical intraepithelial neoplasia (CIN), also known as transformation and dysplasia of cervical intraepithelial cells, is the precancerous lesion of squamous cell carcinoma. CXC chemokine receptor 7 (CXCR7) has been indicated in tumor development and metastasis of multiple malignancies or precancerous lesion. However, the protein expression and function of CXCR7 in different stages of human CIN remains unclear. The present study examined CXCR7 protein expression in cervical tissue samples from 34 patients, including 7 patients with normal cervical tissues (negative control), 10 patients with stage I of CIN (CIN I), 8 patients with CIN II and 9 patients with CIN III. Receiver operating characteristic curves (ROC) were established to evaluate the prognostic value of CXCR7 in differentiating various stages of CIN. Immunohistochemical staining showed that protein expression of CXCR7 was higher in CIN tissues compared with the normal cervical epithelium (P<0.05). High-grade CIN tissues expressed a higher level of CXCR7 compared to low-grade samples. The ROC curve of integral optical density analysis showed that CXCR7 could discriminate CIN I-III from normal cervical epithelium with 88.9% sensitivity and 71.4% specificity, and CIN II-III from the negative control and CIN I with 92.7% sensitivity and 50.0% specificity. ROC curve of area analysis also showed that CXCR7 could discriminate CIN I-III from normal cervical epithelium with 70.4% sensitivity and 100.0% specificity, and CIN II-III from the negative control and CIN I with 50.0% sensitivity and 90.0% specificity. An increase in CXCR7 expression may represent a novel predictor of CIN. The wide expression of CXCR7 in CIN also supports the assumption that CXCR7 plays a role in precancerous lesion progression, as well as proliferation, migration and angiogenesis. PMID- 26870337 TI - Dyslipidemia in patients with systemic lupus erythematosus: Association with disease activity and B-type natriuretic peptide levels. AB - The aim of the present study was to evaluate the association between the levels of lipids and B-type natriuretic peptide (BNP) in systemic lupus erythematosus (SLE) patients with heart failure (HF). A total of 46 patients with active SLE and 40 healthy, age-matched control subjects were studied. BNP was measured by an immunofluorescence assay in fresh plasma. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoprotein (Apo) B, ApoA-I and lipoprotein(a) were assessed. Compared with the control subjects, HDL-C and ApoA-I levels were considerably decreased and TG level increased markedly from SLE patients. The average concentration of HDL-C and ApoA-I in the SLE group with HF was significantly reduced compared to those patients without HF. The results showed that the levels of HDL-C and ApoA-I in SLE patients were negatively correlated with BNP. Disease activity was associated with the TC and TG levels. The present data indicated the presence of a cardiovascular (CV) risk in active SLE with high disease activity, which was demonstrated by the high frequency of dyslipidemia and higher BNP concentrations. Therefore, dyslipoproteinemia may underlie some of the increased risk for CV disease and HF in patients with SLE. PMID- 26870338 TI - ADAMTS13 and 15 are not regulated by the full length and N-terminal domain forms of TIMP-1, -2, -3 and -4. AB - A disintegrin and metalloproteinase with thombospondin motifs (ADAMTS) 13 and 15 are secreted zinc proteinases involved in the turnover of von Willebrand factor and cancer suppression. In the present study, ADAMTS13 and 15 were subjected to inhibition studies with the full-length and N-terminal domain forms of tissue inhibitor of metalloproteinases (TIMPs)-1 to -4. TIMPs have no ability to inhibit the ADAMTS proteinases in the full-length or N-terminal domain form. While ADAMTS13 is also not sensitive to the hydroxamate inhibitors, batimastat and ilomastat, ADAMTS15 can be effectively inhibited by batimastat (Kiapp 299 nM). In conclusion, the present results indicate that TIMPs are not the regulators of these two ADAMTS proteinases. PMID- 26870339 TI - Apoptosis-mediated antiproliferative activity of friedolanostane triterpenoid isolated from the leaves of Garcinia celebica against MCF-7 human breast cancer cell lines. AB - The leaves of Garcinia celebica strongly inhibit the proliferation of MCF-7 human breast adenocarcinoma cell lines. The present study focused on investigating the active anticancer and antiproliferative compound from the G. celebica leaves and assessing its mechanism of action. Ethanol extracts of G. celebica were fractionated based on their polarity using n-hexane, ethyl acetate and water. The antiproliferative properties were tested in vitro against MCF-7 human breast cancer cell lines using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. The active compound was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested for its antiproliferative properties and the mechanism by which it induces apoptosis in MCF-7 cells by western blot analysis of the activated apoptotic proteins. This resulted in the isolation of a friedolanostane triterpenoid, which was determined to be methyl-3alpha, 23-dihydroxy-17,14 friedolanstan-8,14,24-trien-26-oat. This compound inhibited MCF-7 cell proliferation in a time- and dose-dependent manner with IC50 values of 82 and 70 uM for the 24 and 48 h treatments, respectively. Furthermore, the western blot analysis suggested that the compound exerted its anticancer activities by promoting apoptosis through the inhibition of the oncogenic protein Akt, thereby increasing the expression of poly (ADP-ribose) polymerase (PARP) protein. These results suggest that methyl-3alpha,23-dihydroxy-17,14-friedolanstan-8,14,24-trien 26-oat is the anticancer compound found in G. celebica, providing a basis for its potential use in cancer disease management. PMID- 26870340 TI - Internal tandem duplication and tyrosine kinase domain mutations in FLT3 alter the response to daunorubicin in Ba/F3 cells. AB - Internal tandem duplication (ITD) and activating point mutations, mainly at aspartic acid 835 in the tyrosine kinase domain (TKD), are frequently identified in the Fms-related tyrosine kinase 3 (FLT3) receptor gene in acute myeloid leukemia. The ITD in FLT3 (FLT3-ITD) confers resistance to several chemotherapeutic drugs; however, the relative effects of FLT3-ITD and FLT3-TKD mutations on the efficacy of these drugs have not been reported. In the present study, ITD or TKD mutant forms of FLT3 in Ba/F3 cells were expressed, as in the absence of interleukin-3 (IL-3) the growth of these cells is completely dependent on FLT3 oncogenic signals. As a result, the 50% effective dose for daunorubicin was significantly higher in both Ba/F3-FLT3-ITD clones, and also in one of the two Ba/F3-FLT3-TKD clones when cells were cultured without IL-3. This phenomenon was not observed for cytarabine in either Ba/F3-FLT3-ITD or Ba/F3-FLT3-TKD cells. Collectively, these results indicate that ITD and TKD mutations in FLT3 may confer daunorubicin resistance in Ba/F3 cells. PMID- 26870341 TI - Study of the biological features of in vitro cultured gammadelta T cells. AB - The aim of the present study was to investigate the biological features of in vitro cultured gammadelta T cells. The gammadelta T cells were in vitro cultured and on different culture days cell proliferation, phenotype, killing activity and the secretion of cytokines were analyzed. Cell numbers were counted by an automated cell counter, phenotype of the cells and cytokines were analyzed by flow cytometry, and killing activities of the cells against gastric cancer SGC 7901 cells were tested using the cell counting kit-8. From days 7 to 14, in vitro cultured gammadelta T cells enter the exponential phase. On day 14, maximum proliferation fold was observed, and on day 10, the maximum specific growth rate umax was achieved. Flow phenotype cluster of differentiation 3+-T-cell receptor gammadelta+ of the gammadelta T cells in the first 7-17 days achieved a higher proportion and showed no significant differences between 10 days. Secretion of the cytokines interferon-gamma and tumor necrosis factor-alpha gradually increased in the first 7-14 days. The maximum was achieved on day 14, and subsequently began to decrease. The cytolytic activity of the gammadelta T cells to kill the SGC-7901 cells in the first 7-14 days had an improved killing effect, a slight decline from the first 17 days; in the effector cell to target cell (E:T) ratio 20:1, 10:1 and 5:1 conditions, gammadelta T cells kill SGC-7901 cells more effectively than 1:1 and 1:2. In conclusion, gammadelta T cells cultured in the first 7-14 days are suitable for clinical transfusion, and the optimal transfusion time is day 10. An E:T ratio >5:1 is preferred. PMID- 26870342 TI - Association between vascular endothelial growth factor gene polymorphisms and the risk of osteonecrosis of the femoral head: Systematic review. AB - Emerging evidence has shown that vascular endothelial growth factor (VEGF) gene polymorphisms are the key initiators that regulate the expression of the VEGF protein, which has a vital role in osteonecrosis of the femoral head (ONFH). The aim of the present study was to investigate whether polymorphisms of the VEGF genes are associated with the occurrence of ONFH. A comprehensive search was performed on MEDLINE, Embase, Web of Science and China National Knowledge Infrastructure databases before June 2015. Meta-analyses were carried out for the VEGF gene -634G/C polymorphisms (single-nucleotide polymorphism with 3 eligible studies). The pooled odds ratios with 95% confidence intervals (CIs) were used to evaluate the strength of the association. All the eligible studies, involving 1,564 individuals, were identified. According to the inclusion criteria, 3 case control studies were finally included in the meta-analysis. The present meta analysis indicates that the VEGF gene -634G/C polymorphism [CC+GC vs. GG: Response rate (RR)=0.79; 95% CI, 0.67-0.92; GG vs. GC: RR=0.83; 95% CI, 0.72 0.97; GG vs. CC: RR=0.82; 95% CI, 0.72-0.93] is associated with the occurrence of ONFH, and the association with the male subgroup (RR=0.78; 95% CI, 0.65-0.94; P=0.009) is more evident. In conclusion, the present meta-analysis suggests that the VEGF gene -634G/C polymorphism has a significant association with ONFH occurrence among the investigated patients (P<0.01). PMID- 26870343 TI - Formation of size-controllable spheroids using gingiva-derived stem cells and concave microwells: Morphology and viability tests. AB - Human mesenchymal stem cells have previously been isolated and characterized from the gingiva, and gingiva-derived stem cells have been applied for tissue engineering purposes. The present study was performed to generate size controllable stem cell spheroids using concave microwells. Gingiva-derived stem cells were isolated, and the stem cells of 1*105 (group A) or 2*105 (group B) cells were seeded in polydimethylsiloxane-based, concave micromolds with 600 um diameters. The morphology of the microspheres was viewed under an inverted microscope, and the changes in the diameter and cell viability were analyzed. The gingiva-derived stem cells formed spheroids in the concave microwells. The diameters of the spheroids were larger in group A compared to group B. No significant changes in shape or diameter were noted with increases in incubation time. Cell viability was higher in group B at each time point when compared with group A. Within the limits of the study, the size-controllable stem cell spheroids could be generated from gingival cells using microwells. The shape of the spheroids and their viability were clearly maintained during the experimental periods. PMID- 26870344 TI - Tamoxifen induces hepatotoxicity and changes to hepatocyte morphology at the early stage of endocrinotherapy in mice. AB - Clinically, hepatotoxicity is an inevitable side effect during long-term endocrinotherapy in breast cancer patients. Various studies have reported the specific mechanism and protective methods for this long-term hepatotoxicity, however, the short-term influences of tamoxifen (TAM) on hepatocytes remain to be elucidated. The previous study investigated TAM-induced liver injury at the early stage of endocrine treatment. Mice were assigned into 2 groups: The experiment group was administrated with intraperitoneal (i.p.) injection of 6 mg/kg/day TAM for 2 weeks, and the control group was administrated with i.p. injection of physiological saline of the same dose. Body weights in each group were detected every day, and alanine aminotransferase and aspartate aminotransferase levels were measured every 3 days. Small pieces of the liver tissues were obtained and processed for protein extraction, biochemical detection and histopathological analysis 2 weeks later. The results indicated that TAM decreased the mice body weights. Morphologically, with the treatment of TAM for only 2 weeks, at the microscopic and ultrastructural levels the structure of hepatic cords became blurred in sections of the regions, although the lobules of the liver remained visible. Partially, hepatic cells were swelled in spherical shapes. Nuclei appeared to be pyknotic and exhibited uneven chromatin distribution. In addition, it was observed in the transmission electron microscopy analysis that nuclei became pyknotic and unevenly distributed. The majority of the nuclei were endowed with distinct heterochromatin and thick nucleoli. The mitochondrial cristae became vague and disorganized. Finally, western blotting was used and detected a significant increase of the caspase-3 level in the liver tissues. In conclusion, the experiments elucidated that TAM (6 mg/kg/day) would cause hepatotoxicity at the early stage of endocrine treatment in mice, and the underlying mechanism was involved with hepatocyte apoptosis. PMID- 26870345 TI - Assessment of biochemical parameters and characterization of TNFalpha -308G/A and PTPN22 +1858C/T gene polymorphisms in the risk of obesity in adolescents. AB - Obesity is currently considered an inflammatory condition associated with autoimmune diseases, suggesting a common origin. Among other factors, candidate genes may explain the development of this disease. Polymorphisms in the tumor necrosis factor alpha (TNFalpha) and lymphoid protein tyrosine phosphatase (PTPN22) genes lead to an increased risk to development of immune and inflammatory diseases. The aim of the present study was to analyze the biochemical parameters and the effect of the TNFalpha -308G/A and PTPN22 +1858C/T polymorphisms in the susceptibility of adolescents to obesity. A group of 253 adolescent subjects were recruited and classified as obese, overweight or normal weight according to their nutritional status. Anthropometric measurements, clinical and biochemical data were analyzed. DNA was extracted from peripheral blood samples by the phenol-chloroform method, and TNFalpha -308G/A and PTPN22 1858C/T polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assays. Clinical, genetic and biochemical parameters were analyzed to determine the existence of a possible association with the development of obesity. Statistically significant differences in body mass index, insulin, triglyceride levels and homeostatic model assessment for insulin resistance (HOMA-IR) index were observed among the three groups analyzed (P<=0.05). The studied polymorphisms did not confer a risk for developing obesity in the analyzed population (P>0.05); however, significantly low levels of insulin and decreased rates of HOMA-IR were observed in the 1858 CT genotype carriers of the PTPN22 gene. In conclusion, no association between the TNFalpha -308G/A and PTPN22 +1858C/T polymorphisms and the risk to development of obesity in the adolescent population analyzed was observed. However, the 1858 CT genotype of the PTPN22 gene was associated with variations of certain biochemical parameters analyzed. PMID- 26870346 TI - V-PYRRO/NO downregulates mRNA expression levels of leukotriene C4 synthase during hepatic ischemia reperfusion injury in rats via inhibition of the nuclear factor kappaB activation pathway. AB - The aim of the present study was to explore the mechanism underlying the effects of a selective liver nitric oxide (NO) donor, O2-vinyl1-(pyrrolidin-1-yl)-diazen 1-ium-1,2-diolate (V-PYRRO/NO), on the gene expression of leukotriene C4 synthase (LTC4S) during hepatic ischemia/reperfusion (I/R). Adult male Sprague-Dawley rats were divided into 3 groups: Sham (control), I/R and V-PYRRO/NO + I/R groups. The liver was subjected to 1 h of partial hepatic ischemia followed by 5 h of reperfusion, saline or V-PYRRO/NO (1.06 umol/kg/h) administered intravenously. The mRNA expression levels of LTC4S in rat liver tissue were examined by the reverse transcription-polymerase chain reaction method, the protein expression levels of nuclear factor-kappaB (NF-kappaB) p65, p50 and IkappaBalpha in liver cell lysates and nuclear extracts were detected by western blot analysis. Hepatic mRNA expression of LTC4S was lower in V-PYRRO/NO + I/R group compared to the I/R group. In addition, the protein expression levels of NF-kappaB p65 and p50 in the nucleus extract were lower in the V-PYRRO/NO + I/R group when compared with the I/R group. However, the IkappaBalpha protein in the 3 groups was not changed. Immunohistochemistry staining revealed that the I/R liver exhibited strong cytoplasmic and nuclear staining for NF-kappaB p65; however, the V-PYRRO/NO + I/R group liver presented slight cytoplasmic and nuclear staining. In conclusion, V PYRRO/NO may downregulate LTC4S mRNA expression by inhibiting NF-kappaB activation independent of IkappaBalpha during hepatic I/R injury. PMID- 26870347 TI - Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models. AB - 2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect. PMID- 26870348 TI - Mass spectrometric signatures of the blood plasma metabolome for disease diagnostics. AB - In metabolomics, a large number of small molecules can be detected in a single run. However, metabolomic data do not include the absolute concentrations of each metabolite. Generally, mass spectrometry analyses provide metabolite concentrations that are derived from mass peak intensities, and the peak intensities are strictly dependent on the type of mass spectrometer used, as well as the technical characteristics, options and protocols applied. To convert mass peak intensities to actual concentrations, calibration curves have to be generated for each metabolite, and this represents a significant challenge depending on the number of metabolites that are detected and involved in metabolome-based diagnostics. To overcome this limitation, and to facilitate the development of diagnostic tests based on metabolomics, mass peak intensities may be expressed in quintiles. The present study demonstrates the advantage of this approach. The examples of diagnostic signatures, which were designed in accordance to this approach, are provided for lung and prostate cancer (leading causes of mortality due to cancer in developed countries) and impaired glucose tolerance (which precedes type 2 diabetes, the most common endocrinology disease worldwide). PMID- 26870349 TI - Impact of single-nucleotide polymorphisms on radiation pneumonitis in cancer patients. AB - Radiation pneumonitis (RP) is one of the most important dose-limiting toxicities in the radiotherapy of thoracic tumors, which reduces the rate of local tumor control and overall survival and severely affects the patients' quality of life. Single-nucleotide polymorphisms (SNPs) have recently attracted increasing attention as biomarkers for predicting the development of RP. SNPs in inflammation-related, DNA repair-related, stress response-related and angiogenesis-related genes were proved to be associated with RP, with different underlying mechanisms. Radiogenomics focuses on the differences in radiosensitivity caused by gene sequence variation, which may prove helpful in investigating the abovementioned associations. In this review, we aimed to investigate the associations between RP and SNPs reported in recent studies and highlight the main content and prospects of radiogenomics. PMID- 26870350 TI - Expression of zinc finger E-box-binding homeobox factor 1 in epithelial ovarian cancer: A clinicopathological analysis of 238 patients. AB - A growing body of evidence indicates that aberrant activation of epithelial-to mesenchymal transition (EMT) plays a key role in tumor cell invasion and metastasis. Zinc finger E-box-binding homeobox factor 1 (ZEB1), as a crucial mediator of EMT, contributes to the malignant progression of various epithelial tumors. To determine whether ZEB1 is involved in the progression of ovarian cancer, we immunohistochemically evaluated the expression of ZEB1 in 238 cases of epithelial ovarian cancer (EOC) and analyzed its associations with clinicopathological parameters. Positive expression of ZEB1 was observed in 32.8% (78/238) of EOCs and it was found to be significantly associated with advanced tumor stage (P=0.001). The survival analysis indicated that the expression of ZEB1 was associated with a poor 5-year progression-free survival (PFS) (P=0.021). A similar tendency was also observed between the expression of ZEB1 and 5-year overall survival, although it did not reach statistical significance (P=0.118). Moreover, the multivariate analysis demonstrated that ZEB1 expression was an independent risk factor for 5-year PFS in ovarian cancer. Taken together, our data provide evidence that ZEB1 may play a crucial role in promoting aggressive ovarian carcinoma progression. Therefore, ZEB1 may serve as an effectively predictive marker and a potential target for therapeutic intervention in EOC. PMID- 26870351 TI - CXCL10/CXCR3 overexpression as a biomarker of poor prognosis in patients with stage II colorectal cancer. AB - The CXCL10/CXCR3 axis of inflammatory mediators is one of the most important groups of chemokine axes, which has been proven to be a lymphocyte-associated metastasis mediator in several tumors. The term inflammatory adhesions refers to tumors found to be attached to the surrouding tissues during surgery, although no cancer cell infiltration is later identified on pathological examination. The aim of the present study was to investigate the clinical characteristics of stage II colorectal cancer (CRC) and determine the correlation between the CXCL10/CXCR3 axis, inflammatory adhesions and prognosis. Clinicohistopathological data were collected from 401 CRC patients who had undergone R0 resection. Statistical analysis was performed with SPSS 17.0 software. Immunohistochemistry (IHC) was applied to measure the expression of CXCL10 and CXCR3 in 71 recurrent CRC patients, 72 non-recurrent CRC patients and 10 samples from normal peritumoral tissues, all retrieved from the Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Inflammatory adhesions, tumor location and size and the number of high-risk factors for reccurrence were more significantly associated with overall survival (OS) rather than disease-free survival in all the patients as determined by the log-rank and Cox's regression hazard analysis. Further analysis demonstrated that only the presence of inflammatory adhesions (P=0.025) was associated with the OS of recurrent patients. Patients with recurrence exhibited higher CXCR3 (P<0.001) and CXCL10 (P<0.001) expression compared with non-recurrent patients, as determined by IHC. The correlation between clinicopathological variables, CXCL10/CXCR3 expression and survival was also analyzed: Inflammatory adhesions and general tumor type (ulcerated vs. elevated) exhibited a significant correlation with CXCR3; however, the expression of CXCL10 was not significantly correlated with tumor location, histological type, size, gender, or preoperative carcinoembryonic antigen and hemoglobin levels. Furthermore, patients exhibiting a high expression of CXCR3 presented with a higher risk of relapse; among those, patients with inflammatory adhesions always exhibited worse survival. However, no such association was identified for CXCL10 expression. In conclusion, CXCR3 expression may be used as a prognostic marker and may contribute to the prediction of clinical outcome in stage II CRC patients. PMID- 26870353 TI - Tubular adenoma of the common bile duct with uptake in 18F-FDG PET: A case report. AB - A 64-year-old man presented with epigastric discomfort and nausea. Laboratory analyses revealed increased levels of total and direct bilirubin, and increased levels of aminotransferases. Computed tomography revealed the presence of a mass in the distal common bile duct. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography revealed a 25 mm filling defect in the distal common bile duct, and biopsy of the lesion disclosed the presence of tubular adenoma. Using fluorine-18 fluorodeoxyglucose positron emission tomography (18F FDG PET) revealed an increased accumulation of the tracer in the lesion, with a maximum standard uptake value (SUVmax) of 3.3. The patient received a pylorus preserving pancreatoduodenectomy. The histopathological examination revealed a tubular adenoma with low-grade atypia. The patient remains alive 15 months following the surgery, with no evidence of recurrence of the adenoma. 18F-FDG PET has been successfully applied in clinical practice to detect a wide variety of tumor types, including lymphoma, lung, colon and bile duct cancer. In the present study, a case of bile duct adenoma with low-grade atypia was reported, revealing the uptake of 18F-FDG. 18F-FDG PET may be able to detect premalignant tumors of the bile duct, although whether 18F-FDG PET is able to differentially discriminate between diagnoses of adenoma and carcinoma of the bile duct remains to be fully elucidated, and the assessment of further case studies is required. PMID- 26870354 TI - Anaplastic carcinoma of the pancreas arising in an intraductal papillary mucinous neoplasm: A case report. AB - We herein report a case of anaplastic carcinoma of the pancreas arising in an intraductal papillary mucinous neoplasm (IPMN). A 68-year-old Japanese woman was admitted to our hospital complaining of fatigue. Computed tomography revealed an irregular mass in the pancreatic head, which displayed high-signal intensity on diffusion-weighted magnetic resonance imaging. Accordingly, the patient was diagnosed with pancreatic cancer and underwent pancreaticoduodenectomy. The histopathological findings revealed intraductal papillary proliferative changes involving the main and branch ducts of the pancreatic head. Based on the immunohistochemistry results, the intraductal lesion was diagnosed as IPMN. The pathological diagnosis for the invasive carcinoma was anaplastic giant-cell carcinoma of the pancreas (ACP), and the focus of IPMN dedifferentiation to ACP was found to be located at the periphery of the IPMN. At 18 months postoperatively, the patient remains disease-free. PMID- 26870355 TI - Feasibility of intensity-modulated radiotherapy combined with gemcitabine and S-1 for patients with pancreatic cancer. AB - The aim of the present study was to establish whether intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine and S-1 is a feasible treatment option for patients with locally advanced pancreatic ductal adenocarcinoma. Patients with pancreatic ductal adenocarcinoma were prospectively enrolled. An IMRT dose of 50.4 Gy in 28 fractions with concurrent gemcitabine at a dose of 600 mg/m2 and S-1 at a dose of 60 mg were administrated. Adverse events and associated dosimetric factors were assessed. Between February 2012 and January 2014, 17 patients with borderline resectable and 4 with unresectable pancreatic cancer were enrolled. None of the patients experienced grade 3 or worse nausea and vomiting. The planning target volume (>=200 vs. <200 ml) was a statistically significant predictive factor for neutrocytopenia (>=500 vs. 500/ul, P=0.02). Concurrent IMRT with gemcitabine and S-1 for patients with locally advanced pancreatic cancer is feasible, with tolerable hematological toxicities and low gastrointestinal toxicities. PMID- 26870352 TI - Presentation of multiple myeloma mimicking bone metastasis from colon adenocarcinoma: A case report and literature review. AB - We herein present the case report of a 83-year-old female patient who had undergone right colon resection for adenocarcinoma 2 years earlier, and developed osteolytic lesions of the right femur 6 months ago. A roentgenogram of the right thigh, technetium-99m phosphate bone scintigraphy and combined 18F-fluoro-2-deoxy D-glucose positron emission tomography/computed tomography imaging were performed, and the results revealed multiple osteolytic lesions in the humerus bilaterally, the right scapula and the right femur. The lesions were suspected to be colon cancer metastases. To improve the quality of life of the patient, palliative surgery was performed. However, the intraoperative biopsy of the focal lesions and immunohistochemical evaluation revealed multiple myeloma (MM). Chemotherapy was administered 2 weeks after surgery and the patient recovered uneventfully. The manifestations of MM and bone metastases are occasionally similar. Although the coexistence of the two diseases is rare, both conditions should be considered in the differential diagnosis of osteolytic lesions. PMID- 26870356 TI - Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer. AB - There are limited studies reported that describe the efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. The present study examined the therapeutic efficacy of eribulin and trastuzumab in the treatment of recurrent breast cancer. Between October 2011 and August 2013, 5 recurrent breast cancer patients who were treated with eribulin and trastuzumab were included in the study. The cancer stages in the 5 women who received this regimen were stage IIIB in 1 (20%) and stage IV in 4 (80%). The sites of recurrence were the lung in 3 patients, liver in 2, bone in 1, brain in 1, supraclavicular lymph nodes in 1, infraclavicular lymph nodes in 1 and mediastinal lymph nodes in 1. The median number of prior treatment regimens was 5 (range, 5-11). Complete response was achieved in 0 patients, 1 achieved partial response, 3 had stable disease, and 1 had progressive disease. The overall response rate was 20%, and the clinical benefit rate was 80%. Patients also reported grade 3/4 neutropenia (80.0%). However, hematological toxicity was reversible and manageable. The most common grade 3/4 nonhematological toxicities were fatigue (20.0%), peripheral neuropathy (20.0%) and appetite loss (20.0%). No patients withdrew from treatment, and favorable compliance was achieved in the study. The results indicated that eribulin and trastuzumab have the potential to be one of the drugs for treatment of recurrent breast cancer. PMID- 26870357 TI - Determination of prognosis of Philadelphia chromosome-negative myeloproliferative neoplasms with a simple clinical examination: Retrospective analysis of 71 patients in a single institution. AB - Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF), are clonal hematopoietic diseases. A single-institution retrospective analysis was performed, including 71 MPN patients diagnosed at the Hakodate Municipal Hospital between April, 2001 and April, 2014, and certain clinical characteristics were identified as effective prognostic factors. The patients were categorized by risk factor scoring based on age, number of abnormal blood cell lineages and splenomegaly at diagnosis, and the association between this categorization and prognosis was analyzed using a statistical procedure. The effect of Janus kinase 2 (JAK2) V617F mutation on prognosis was also investigated. The MPN patients were consolidated into three risk groups based on the margin of intergroup survival differences: i) Score 1-2 (n=23), ii) score 3 (n=24) and iii) score 4-5 (n=24). MPN patients with scores of 4 or 5 exhibited poorer overall survival (OS) compared with those with lower scores (P<0.001). In addition, there were significant differences in event-free survival (EFS) among scoring groups (P=0.0059). PV and ET had a better prognosis compared with PMF, although this analysis suggested that PV and ET patients with scores of 4 or 5 may have a poorer prognosis in terms of OS (P=0.0052) and EFS (P=0.022) and should be closely followed up. We observed no significant prognostic effect of the JAK2V167F mutation for OS (P=0.28) or EFS (P=0.17). Our results suggested that a simple scoring system based on age, blood cell counts and presence of splenomegaly at diagnosis may be used for the long-term prognosis of MPN patients. PMID- 26870358 TI - Epiglottic diffuse B-cell malignant lymphoma: A case report. AB - A 55-year-old male patient was admitted to our department with complaints of dysphagia and throat soreness for 2 months. A tumor of the left epiglottis, with an irregular surface, was identified by video laryngoscopy. The diagnosis of malignant lymphoma was confirmed by biopsy during laryngomicrosurgery. The atypical diffuse lymphocytic lymphoma was positive for CD20 and Bcl-2, and negative for CD3, CD10 and Bcl-1. The diagnosis was diffuse large B-cell malignant lymphoma. The patient was treated with eight cycles of rituximab with cyclophosphamide + doxorubicin + vincristine + prednisolone (R-CHOP regimen). This is a rare case of extranodal non-Hodgkin lymphoma occurring in the epiglottis. PMID- 26870359 TI - TERT promoter mutations are rare in bone and soft tissue sarcomas of Japanese patients. AB - Recurrent hot-spot mutations in the telomerase reverse transcriptase (TERT) promoter have been reported in various types of tumor. In several tumor types, TERT promoter mutations are associated with poor clinical outcomes. TERT promoter mutations are reported to be rare in soft tissue tumors, with the exception of myxoid liposarcoma (MLS). Our previous study reported that TERT promoter mutations occurred in a subset of solitary fibrous tumors (SFTs) and were associated with adverse clinical outcomes in Japanese individuals. The site specific frequency (e.g. central nervous or soft tissue origin) of TERT promoter mutations in our SFT cases appeared to be different from previously reported values in a European population. These findings prompted the present study to elucidate the potential role of ethnic background in the different frequencies of TERT promoter mutations in bone and soft tissue sarcomas. In the present study, TERT promoter mutations were examined in 180 cases of bone and soft tissue sarcomas. TERT promoter region mutations were identified in 10 cases [5 SFTs, 3 MLSs, 1 undifferentiated pleomorphic sarcoma (UPS) and 1 malignant granular cell tumor]. All mutations were C228T. The frequencies of TERT promoter mutation in MLS and UPS were 23.1 (3/13) and 5% (1/20), respectively. Only 1/5 patients with TERT-mutated tumors experienced local recurrence or distant metastasis. The present study revealed the first case of a malignant granular cell tumor with a TERT promoter mutation and revealed that the frequency of TERT promoter mutations in MLSs of Japanese patients is lower compared with that reported in German patients, providing evidence of a possible ethnic difference in the frequency of TERT promoter mutations. PMID- 26870360 TI - Expression of metabotropic glutamate receptor 4 in osteosarcoma. AB - Metabotropic glutamate receptor 4 (mGluR4) has been associated with the pathogenesis of osteosarcoma. The aim of this study was to investigate mGluR4 expression and its clinical significance in osteosarcoma patients. mGluR4 expression was investigated using immunohistochemistry (IHC) in 58 osteosarcomas and 32 giant-cell tumors of bone. The correlations between mGluR4 expression and clinicopathological characteristics were analyzed with the Chi-squared test and survival curves were generated using the Kaplan-Meier method. The IHC results demonstrated that 20.69% (12/58) of the osteosarcomas and 43.75% (14/32) of the giant-cell tumors were mGluR4-positive. The statistical analysis revealed that mGluR4 expression was correlated with gender, age, Enneking stage and tumor volume in osteosarcomas (P<0.05). In the multivariate stepwise Cox regression analysis, Enneking stage was found to be statistically significantly associated with survival (P<0.05) and the survival analysis demonstrated that the survival probability was significantly higher in patients with higher mGluR4 expression compared with those with lower expression (P<0.05). Therefore, mGluR4 expression may be used to estimate the prognosis of osteosarcoma patients. PMID- 26870361 TI - Management of the N0 neck in recurrent laryngeal squamous cell carcinoma. AB - The most effective therapeutic approach for the node-negative (N0) neck in patients with recurrent laryngeal squamous cell carcinoma (SCC) remains a subject of dispute. In the present study, the records of 163 patients with recurrent laryngeal SCC were retrospectively reviewed. All patients had a N0 neck at recurrence. At the time of recurrence, the N0 neck was managed using a wait-and see strategy (observation group) or treatment (treatment group). A total of 125 (76.7%) patients accepted the wait-and-see strategy and 38 (23.3%) patients underwent treatments, including surgery, radiotherapy and/or chemotherapy. The Kaplan-Meier method with the computation of log-rank was used for analysis of survival. The t-test, chi2 test or Fisher's exact test was used for comparisons of non-survival data in the groups. P<0.05 was considered to indicate a statistically significant difference in the two-sided tests. The 3- and 5-year overall survival rates after recurrence were 64.5 and 54.6% for the observation group, and 49.9 and 42.5% for the treatment group, respectively (P=0.011). The present study suggests that a wait-and-see policy is a satisfactory management option for the N0 neck in recurrent laryngeal SCC. PMID- 26870362 TI - Prognostic value of cancer stem cell marker CD133 expression in esophageal carcinoma: A meta-analysis. AB - CD133 has been identified as a putative neoplastic stem cell marker in esophageal carcinoma. However, the prognostic value of CD133 overexpression in patients with esophageal carcinoma remains controversial. A meta-analysis of previous studies was performed, in order to assess the association of CD133 overexpression with the clinicopathological characteristics of esophageal carcinoma patients. A total of 7 studies, including 538 patients, were subjected to the final analysis. Our results indicated that a positive CD133 expression was significantly associated with lymph node metastasis [odds ratio (OR)=3.09, 95% confidence interval (CI): 1.93-4.95; P<0.00001], clinical stage (OR=4.26, 95% CI: 1.55-11.73; P=0.005) and histopathological grade (OR=2.40, 95% CI: 1.16-4.94; P=0.02). There was no statistically significant association of CD133 with depth of invasion (OR=1.89, 95% CI: 0.42-8.43; P=0.41). Based on the results of this study, we concluded that CD133 is an efficient prognostic factor in esophageal carcinoma. Higher CD133 expression is significantly associated with lymph node metastasis, clinical stage and histopathological grade. PMID- 26870363 TI - Outcomes and toxicity of radiotherapy for refractory bone and soft tissue sarcomas. AB - Surgical resection is a well-established treatment option for sarcoma. However, anatomical barriers often hamper radical surgical procedures. The treatment of unresectable sarcoma, including local or distant failures following initial treatment, is challenging. The aim of the present study was to analyze the outcome of radiotherapy (RT) for refractory sarcoma, including unresectable, metastatic and recurrent disease, following radical treatment. We retrospectively reviewed a total of 67 tumors in 28 patients who were treated with RT between 2007 and 2014. Clinical target volume (CTV) was generally not defined in a preventive manner; therefore, in the majority of the cases, CTV equaled the gross tumor volume. The total delivered dose, number of fractions and biological equivalent dose were 52 (range, 40-69), 10 (range, 4-24) and 92.2 (range, 56 119.6) Gy, respectively. Only 1 patient developed local failure, with a median follow-up of 11 months (range, 1-59 months). Therefore, the 12-month progression free survival rate for 67 sites was 96.8%. The overall survival rates at 12 and 36 months were 75.8 and 30.2%, respectively. A total of 2 patients developed grade >2 toxicities, including grade 3 mucositis and grade 4 pericardial effusion. Our results demonstrated that radical RT using modern techniques is highly feasible, achieves excellent local control, and may be an effective treatment option for refractory sarcoma. PMID- 26870364 TI - Unplanned discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia. AB - This study was conducted to investigate the outcomes of patients with chronic myeloid leukemia (CML) who discontinued tyrosine kinase inhibitor (TKI) treatment. A single-center retrospective analysis was performed, including 46 chronic-phase (CP) CML patients who achieved complete molecular response (CMR) with TKIs. TKI treatment was discontinued in 13 patients based on their requests. The BCR-ABL transcript levels were monitored in the peripheral blood by quantitative polymerase chain reaction analysis following treatment discontinuation. Of the 13 patients who discontinued TKI treatment, 7 remained in CMR, with a median follow-up of 26 months (range, 10-60 months). The remaining 6 patients lost CMR following TKI discontinuation; 2 of these patients achieved a second CMR following re-administration of TKIs, 2 patients spontaneously achieved CMR and 2 remained in complete hematological response (CHR) without TKI treatment with a median follow-up of 29.5 months (range, 10-52 months). In conclusion, the survival of patients who lost CMR following TKI discontinuation may not be affected, even without re-administration of TKIs. Vigilant observation is recommended for such patients. The limitations of this study included the small patient sample, retrospective design and patient heterogeneity. Therefore, the results must be interpreted with caution. PMID- 26870365 TI - Clinical pretreatment risk factors and prediction of outcome using gallium 67 scintigraphy in patients with Hodgkin's lymphoma. AB - This study was conducted to investigate the prognostic effect and implications of gallium 67 scintigraphy (gallium scan) at mid-treatment and at the end of first line treatment in patients with early- and advanced-stage Hodgkin's lymphoma (HL). A total of 216 HL patients were included in the study. Gallium scan was performed at mid-treatment and at the end of first-line treatment. The overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan Meier method. The log-rank test was used to identify univariate predictors of EFS and OS. For early-stage disease, bulky mediastinal involvement (yes vs. no, 98 vs. 79%, respectively; P=0.01), erythrocyte sedimentation rate (good vs. adverse, 98 vs. 88%, respectively; P=0.03), presence of B symptoms (no vs. yes, 94 vs. 78%, respectively; P=0.006), post-chemotherapy disease status [complete response (CR) vs. unconfirmed CR (uCR) vs. partial response (PR) vs. progressive disease (PGR), 95 vs. 90 vs. 87 vs. 0%, respectively; P<0.01] and gallium scan at mid treatment and at the end of treatment (negative vs. positive, 88 vs. 20%, P<0.001; and 85 vs. 10%, P<0.001, respectively) significantly affected the EFS. In addition, age (<50 vs. >=50 years, 96 vs. 78%, respectively; P=0.01), presence of B symptoms (no vs. yes, 97 vs. 87%, respectively; P=0.03), post-chemotherapy disease status (CR vs. uCR vs. PR vs. PGR, 95 vs. 90 vs. 90 vs. 0%, respectively; P<0.01) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 87 vs. 60%, P<0.001; and 95 vs. 0%, P<0.001, respectively) significantly affected the OS. For advanced-stage disease, Hassenclever index (1-3 vs. 4-6, 80 vs. 57%, respectively; P=0.05) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 84 vs. 18%, P<0.001; and 84 vs. 0%, P<0.001, respectively) significantly affected the EFS, whereas age at diagnosis (<50 vs. >=50 years, 92 vs. 78%, respectively; P=0.04), Hassenclever index (1-3 vs. 4-6, 86 vs. 61%, respectively; P=0.04) and gallium scan results at mid-treatment and at the end of treatment (negative vs. positive, 98 vs. 40%, P<0.001; and 97 vs. 23%, P<0.001, respectively) significantly affected the OS. On the multivariate analysis, gallium scan at the end of first-line treatment retained statistical significance in terms of EFS and OS. In conclusion, post-chemotherapy gallium scan is an important prognostic factor in patients with early- or advanced-stage HL and a predictor of adverse outcome. PMID- 26870366 TI - Prognostic role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 in various cancers: A meta-analysis. AB - Several studies have investigated the correlation between the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and cancer prognosis, with inconsistent results. Therefore, a meta-analysis was conducted to identify the potential correlation after pooling data from eligible studies. PubMed/Medline, Web of Science and The Cochrane Library electronic databases were searched for eligible studies on the prognostic role of MALAT1 in cancer, from inception to January, 2015. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to summarize the effect. A total of 1,198 patients from 10 studies were included in the analysis. The results suggested that MALAT1 expression was significantly associated with overall survival (HR=2.07, 95% CI: 1.67-2.56), disease-free survival (HR=2.60, 95% CI: 1.69-4.00) and recurrence-free survival (HR=3.28, 95% CI: 1.52-7.09). MALAT1 was also found to be significantly associated with tumor size (P=0.013). Overall, MALAT1 expression may be considered as a potential prognostic factor for cancer patients. PMID- 26870367 TI - Novel agent induction therapy alone or followed by autologous stem cell transplantation in younger patients with multiple myeloma: A single-center retrospective study of 114 cases. AB - To define the role of autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM) in the era of novel agents, we analyzed follow-up data of patients treated by these agents alone or followed by ASCT. From January, 2008 to December, 2012, 136 patients with de novo MM, aged <65 years, completed bortezomib- or thalidomide-based induction therapy and 114 patients achieved at least a partial response (PR). A total of 42 patients underwent ASCT. After a median follow-up of 39 months (range, 5-74 months), the median progression-free survival (PFS) was 23 months in the non-ASCT group vs. 42 months in the ASCT group (P=0.001), and the 5-year overall survival (OS) rate was 58.9 vs. 81.2%, respectively (P=0.03). The multivariate analysis revealed that complete response (CR) and maintenance therapy (MT) were independent factors of improved OS in both groups. Moreover, a subgroup analysis was performed according to the response status to evaluate the role of ASCT and MT. In the CR subgroup, neither ASCT nor MT exerted a significant effect on PFS or OS. In the very good PR subgroup, ASCT after MT (ASCT/MT) significantly improved PFS, but not OS. In patients exhibiting PR, ASCT/MT significantly prolonged PFS and OS. Therefore, ASCT in the era of novel agents maintains an important role in younger MM patients, particularly those achieving a PR after induction therapy. Furthermore, MT is a key factor associated with long-term survival in all MM patients. PMID- 26870368 TI - Follicular cholangitis associated with focal biliary stricture treated with left hepatectomy after 8 years of follow-up: A rare case report. AB - Follicular cholangitis may lead to severe focal biliary stricture, which is difficult to distinguish from cholangiocarcinoma. This is the report of a rare case of follicular cholangitis associated with an intrahepatic focal biliary stricture in a 69-year-old woman. The patient visited our hospital for upper abdominal pain in 2006. Computed tomography revealed common bile duct stones and focal stricture of the left intrahepatic duct. Endoscopic retrograde cholangiopancreatography revealed a severe B3 stricture and dilation of the peripheral biliary tract. Repeated cytology revealed no malignancy. The patient was followed up for 8 years and repeated attacks of cholangitis severely compromised her quality of life. A left hepatectomy was performed, and the pathological findings were consistent with follicular cholangitis. It is generally difficult to make a definitive diagnosis after identifying a biliary stricture, and the stricture is often treated with surgical resection. The clinical presentation and radiological findings of follicular cholangitis are similar to those of cholangiocarcinoma; therefore, if a conservative approach is selected, frequent follow-up is recommended. The present case suggests that follicular cholangitis should be considered in the differential diagnosis of biliary stricture. PMID- 26870369 TI - Adequacy of endobronchial ultrasound-guided transbronchial needle aspiration samples processed as histopathological samples for genetic mutation analysis in lung adenocarcinoma. AB - Phenotyping non-small-cell lung cancer is becoming increasingly important with the advent of molecular testing. Tumours harbouring somatic mutations in the gene that encodes for the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) have been found to increase responsiveness to tyrosine kinase inhibitors. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for mediastinal node sampling. The available prospective data on EBUS-TBNA sample suitability for molecular profiling are currently limited. The aim of this prospective study was to evaluate the adequacy of EBUS-TBNA samples for EGFR and anaplastic lymphoma kinase (ALK) genetic mutation analysis in confirmed primary lung adenocarcinomas. We conducted a prospective analysis of 410 consecutive patients referred for EBUS TBNA between 2010 and 2014. Rapid on-site cytological evaluation was not used. The samples were obtained using 21-gauge (21G) or 22G needles and were prepared as histopathological samples. A total of 91 samples were confirmed as lung adenocarcinomas and 80 of these samples were sent for EGFR mutation analysis. EBUS-TBNA had a diagnostic accuracy of 98.3% for malignancy. EGFR mutation testing was possible in 79/80 cases (98.75%). EGFR mutations were detected in 5/80 (6.3%) samples. ALK gene analysis, which became available during the study period, was requested and successfully performed in 21/21 samples (100%). The total combined genotyping success rate was 100/101 (99.0%). This UK study confirmed the high clinical utility of EBUS-TBNA samples processed as histopathological specimens for EGFR and ALK genotyping in primary lung adenocarcinoma. The needle gauge did not affect genotyping efficacy. PMID- 26870370 TI - Angiomyolipoma of the rib: A rare case report. AB - Angiomyolipoma is a benign mesenchymal tumor, most commonly arising from the kidney. With the exception of the liver, extrarenal angiomyolipoma is an infrequent entity that may be misdiagnosed as other tumors. Angiomyolipoma occurring in the skeleton is an extremely rare occurrence and often difficult to differentiate from other bone diseases. We herein present a case of angiomyolipoma in the rib of a 44-year-old male patient, a highly unusual location for this type of tumor. Angiomyolipoma of the skeleton usually exhibits an infiltrative tendency. Although this clinical entity is rare, angiomyolipoma should be considered in the differential diagnosis of skeletal lesions, particularly in patients presenting with imaging findings of fat within the lesions. PMID- 26870371 TI - Clinical outcome of immunotherapy with dendritic cell vaccine and cytokine induced killer cell therapy in hepatobiliary and pancreatic cancer. AB - The aim of this study was to determine the therapeutic effects of adoptive immunotherapy following dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy and evaluate its cytotoxicity, survival benefits and quality of life (QOL) changes in patients with hepatobiliary and pancreatic cancer (HPC). We performed a retrospective analysis of 407 clinical cases, including 77 patients with HPC who received immunotherapy with DC vaccine and CIK cells (I group) and 330 patients with similar characteristics who underwent baseline treatment but did not receive immunotherapy [non-immunotherapy (NI) group)] as the control group. After a follow-up period of 294+/-207.5 days, the median survival time (MST) of the two groups was compared using the Kaplan-Meier method. In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The most notable adverse events included fever (28%), insomnia (25%), anorexia (17%), skin rash (12%) and arthralgia (31%). No severe toxicities were observed in patients in the I group; in addition, the MST was significantly longer in the I group compared with that in the NI group (P=0.014). Thus, the DC vaccine and CIK cell therapy was associated with mild adverse effects, but was able to induce an immune response and effectively eliminate tumor cells, thereby improving the QOL and prolonging the MST of the patients. PMID- 26870372 TI - Increased erythropoietin levels as a biomarker of pancreatic adenocarcinoma: A case report. AB - Pancreatic cancer is one of the deadliest cancers commonly diagnosed at an advanced stage. Early diagnosis is crucial for the timely and potentially curative treatment of this highly fatal disease. Although screening tests have improved the survival rate in malignancies such as colon, breast, cervical and prostate cancer, there is currently no effective screening method available for the early detection of pancreatic cancer. As the sensitivity and specificity of existing biomarkers, such as carbohydrate antigen 19-9, for the early detection of pancreatic cancer is low, there is a pressing need for the identification of novel cancer markers. An increase in erythropoietin (EPO) levels has been observed in several cases of pancreatic neoplasms. However, the potential role of EPO as a biomarker of pancreatic cancer or malignant transformation requires further investigation. We herein present a case of increased EPO levels in an adult male patient with stage IV pancreatic cancer. PMID- 26870373 TI - Asymptomatic Paget's disease of bone in a 62-year-old Nigerian man: three years post-alendronate therapy. AB - Paget's disease is a chronic and progressive disorder of bone characterized by focal areas of excessive osteoclastic resorption accompanied by a secondary increase in the osteoblastic activity. Paget's disease of bone (PBD) is a rare endocrine disease especially among Africans and Asians. Hence the detection of a case in a middle-aged Nigerian is of interest. We present the case of a 62-year old Nigerian man in apparent good health who was found to have a markedly elevated serum total alkaline phosphatase (ALP) of 1179 U/l (reference range, 40 115 U/l) 4 years ago during a routine medical check-up in the USA. He had no history suggestive of PDB and also had no known family history of bone disease. Examination findings were not remarkable except for a relatively large head. A repeat ALP in our centre was 902 U/l (reference range, 40-120 U/l). Cranial CT scan showed diffuse cranial vault thickening consistent with Paget's disease which was confirmed by Tc-99m hydroxymethylene diphosphonate. He was placed on 40 mg alendronate tablets daily for 6 months. The patient has remained asymptomatic and has been in continuing biochemical remission during the 3-year follow-up period. The most recent ALP result is 88 U/l (reference range, 30-132 U/l) in April 2015. LEARNING POINTS: Serum total alkaline phosphatase remains a sensitive marker of bone turnover and an isolated increase above the upper limit of normal warrants more intense scrutiny in form of investigations targeted at excluding PD.Paget's disease is very rare but can occur in the Africans as seen in this Nigerian man and most patients are asymptomatic.Asymptomatic patients can benefit from treatment if disease is active, polyostotic or the lesions are located in bones with future risk of complications such as long bones, vertebrae and skull.Bisphosphonates are still the mainstay of treatment and alendronate is a useful therapeutic option for treatment. PMID- 26870374 TI - Crystal engineering and IUCrJ. AB - Crystal engineering is discussed, along with its three key concepts: crystal packing; the design of solids; and physical and chemical properties. PMID- 26870375 TI - CryoEM at IUCrJ: a new era. AB - In this overview, we briefly outline recent advances in electron cryomicroscopy (cryoEM) and explain why the journal IUCrJ, published by the International Union of Crystallography, could provide a natural home for publications covering many present and future developments in the cryoEM field. PMID- 26870376 TI - Perovskites take the lead in local structure analysis. AB - Materials with the much-loved perovskite structure are being used to develop and test new methods for interpreting local structural arrangements in crystals, and these methods are in turn uncovering unexpected new structural insight. PMID- 26870377 TI - Peptide binding to a bacterial signal peptidase visualized by peptide tethering and carrier-driven crystallization. AB - Bacterial type I signal peptidases (SPases) are membrane-anchored serine proteases that process the signal peptides of proteins exported via the Sec and Tat secretion systems. Despite their crucial importance for bacterial virulence and their attractiveness as drug targets, only one such enzyme, LepB from Escherichia coli, has been structurally characterized, and the transient nature of peptide binding has stymied attempts to directly visualize SPase-substrate complexes. Here, the crystal structure of SpsB, the type I signal peptidase from the Gram-positive pathogen Staphylococcus aureus, is reported, and a peptide tethering strategy that exploits the use of carrier-driven crystallization is described. This enabled the determination of the crystal structures of three SpsB peptide complexes, both with cleavable substrates and with an inhibitory peptide. SpsB-peptide interactions in these complexes are almost exclusively limited to the canonical signal-peptide motif Ala-X-Ala, for which clear specificity pockets are found. Minimal contacts are made outside this core, with the variable side chains of the peptides accommodated in shallow grooves or exposed faces. These results illustrate how high fidelity is retained despite broad sequence diversity, in a process that is vital for cell survival. PMID- 26870378 TI - Total scattering and pair distribution function analysis in modelling disorder in PZN (PbZn1/3Nb2/3O3). AB - The ability of the pair distribution function (PDF) analysis of total scattering (TS) from a powder to determine the local ordering in ferroelectric PZN (PbZn1/3Nb2/3O3) has been explored by comparison with a model established using single-crystal diffuse scattering (SCDS). While X-ray PDF analysis is discussed, the focus is on neutron diffraction results because of the greater extent of the data and the sensitivity of the neutron to oxygen atoms, the behaviour of which is important in PZN. The PDF was shown to be sensitive to many effects not apparent in the average crystal structure, including variations in the B-site-O separation distances and the fact that <110> Pb(2+) displacements are most likely. A qualitative comparison between SCDS and the PDF shows that some features apparent in SCDS were not apparent in the PDF. These tended to pertain to short-range correlations in the structure, rather than to interatomic separations. For example, in SCDS the short-range alternation of the B-site cations was quite apparent in diffuse scattering at (1/2 1/2 1/2), whereas it was not apparent in the PDF. PMID- 26870379 TI - Comparison between diffraction contrast tomography and high-energy diffraction microscopy on a slightly deformed aluminium alloy. AB - The grain structure of an Al-0.3 wt%Mn alloy deformed to 1% strain was reconstructed using diffraction contrast tomography (DCT) and high-energy diffraction microscopy (HEDM). 14 equally spaced HEDM layers were acquired and their exact location within the DCT volume was determined using a generic algorithm minimizing a function of the local disorientations between the two data sets. The microstructures were then compared in terms of the mean crystal orientations and shapes of the grains. The comparison shows that DCT can detect subgrain boundaries with disorientations as low as 1 degrees and that HEDM and DCT grain boundaries are on average 4 um apart from each other. The results are important for studies targeting the determination of grain volume. For the case of a polycrystal with an average grain size of about 100 um, a relative deviation of about <=10% was found between the two techniques. PMID- 26870380 TI - Protein crystal structure from non-oriented, single-axis sparse X-ray data. AB - X-ray free-electron lasers (XFELs) have inspired the development of serial femtosecond crystallography (SFX) as a method to solve the structure of proteins. SFX datasets are collected from a sequence of protein microcrystals injected across ultrashort X-ray pulses. The idea behind SFX is that diffraction from the intense, ultrashort X-ray pulses leaves the crystal before the crystal is obliterated by the effects of the X-ray pulse. The success of SFX at XFELs has catalyzed interest in analogous experiments at synchrotron-radiation (SR) sources, where data are collected from many small crystals and the ultrashort pulses are replaced by exposure times that are kept short enough to avoid significant crystal damage. The diffraction signal from each short exposure is so 'sparse' in recorded photons that the process of recording the crystal intensity is itself a reconstruction problem. Using the EMC algorithm, a successful reconstruction is demonstrated here in a sparsity regime where there are no Bragg peaks that conventionally would serve to determine the orientation of the crystal in each exposure. In this proof-of-principle experiment, a hen egg-white lysozyme (HEWL) crystal rotating about a single axis was illuminated by an X-ray beam from an X-ray generator to simulate the diffraction patterns of microcrystals from synchrotron radiation. Millions of these sparse frames, typically containing only ~200 photons per frame, were recorded using a fast-framing detector. It is shown that reconstruction of three-dimensional diffraction intensity is possible using the EMC algorithm, even with these extremely sparse frames and without knowledge of the rotation angle. Further, the reconstructed intensity can be phased and refined to solve the protein structure using traditional crystallographic software. This suggests that synchrotron-based serial crystallography of micrometre-sized crystals can be practical with the aid of the EMC algorithm even in cases where the data are sparse. PMID- 26870381 TI - Rapid experimental SAD phasing and hot-spot identification with halogenated fragments. AB - Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a 'magic bullet' that is capable of binding at many of the ligand 'hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are 'hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals. PMID- 26870382 TI - Yes, one can obtain better quality structures from routine X-ray data collection. AB - Single-crystal X-ray diffraction structural results for benzidine dihydrochloride, hydrated and protonated N,N,N,N-peri(dimethylamino)naphthalene chloride, triptycene, dichlorodimethyltriptycene and decamethylferrocene have been analysed. A critical discussion of the dependence of structural and thermal parameters on resolution for these compounds is presented. Results of refinements against X-ray data, cut off to different resolutions from the high-resolution data files, are compared to structural models derived from neutron diffraction experiments. The Independent Atom Model (IAM) and the Transferable Aspherical Atom Model (TAAM) are tested. The average differences between the X-ray and neutron structural parameters (with the exception of valence angles defined by H atoms) decrease with the increasing 2thetamax angle. The scale of differences between X-ray and neutron geometrical parameters can be significantly reduced when data are collected to the higher, than commonly used, 2thetamax diffraction angles (for Mo Kalpha 2thetamax > 65 degrees ). The final structural and thermal parameters obtained for the studied compounds using TAAM refinement are in better agreement with the neutron values than the IAM results for all resolutions and all compounds. By using TAAM, it is still possible to obtain accurate results even from low-resolution X-ray data. This is particularly important as TAAM is easy to apply and can routinely be used to improve the quality of structural investigations [Dominiak (2015 ?). LSDB from UBDB. University of Buffalo, USA]. We can recommend that, in order to obtain more adequate (more accurate and precise) structural and displacement parameters during the IAM model refinement, data should be collected up to the larger diffraction angles, at least, for Mo Kalpha radiation to 2thetamax = 65 degrees (sin thetamax/lambda < 0.75 A(-1)). The TAAM approach is a very good option to obtain more adequate results even using data collected to the lower 2thetamax angles. Also the results of translation-libration-screw (TLS) analysis and vibrational entropy values are more reliable for 2thetamax > 65 degrees . PMID- 26870383 TI - Advanced electron crystallography through model-based imaging. AB - The increasing need for precise determination of the atomic arrangement of non periodic structures in materials design and the control of nanostructures explains the growing interest in quantitative transmission electron microscopy. The aim is to extract precise and accurate numbers for unknown structure parameters including atomic positions, chemical concentrations and atomic numbers. For this purpose, statistical parameter estimation theory has been shown to provide reliable results. In this theory, observations are considered purely as data planes, from which structure parameters have to be determined using a parametric model describing the images. As such, the positions of atom columns can be measured with a precision of the order of a few picometres, even though the resolution of the electron microscope is still one or two orders of magnitude larger. Moreover, small differences in average atomic number, which cannot be distinguished visually, can be quantified using high-angle annular dark-field scanning transmission electron microscopy images. In addition, this theory allows one to measure compositional changes at interfaces, to count atoms with single atom sensitivity, and to reconstruct atomic structures in three dimensions. This feature article brings the reader up to date, summarizing the underlying theory and highlighting some of the recent applications of quantitative model-based transmisson electron microscopy. PMID- 26870385 TI - Correction. AB - [This corrects the article DOI: 10.1136/bmjdrc-2015-000123.]. PMID- 26870384 TI - Complications of indwelling pleural catheter use and their management. AB - The growing utilisation of indwelling pleural catheters (IPCs) has put forward a new era in the management of recurrent symptomatic pleural effusions. IPC use is safe compared to talc pleurodesis, though complications can occur. Pleural infection affects <5% of patients, and is usually responsive to antibiotic treatment without requiring catheter removal or surgery. Pleural loculations develop over time, limiting drainage in 10% of patients, which can be improved with intrapleural fibrinolytic therapy. Catheter tract metastasis can occur with most tumours but is more common in mesothelioma. The metastases usually respond to analgaesics and/or external radiotherapy. Long-term intermittent drainage of exudative effusions or chylothorax can potentially lead to loss of nutrients, though no data exist on any clinical impact. Fibrin clots within the catheter lumen can result in blockage. Chest pain following IPC insertion is often mild, and adjustments in analgaesics and drainage practice are usually all that are required. As clinical experience with the use of IPC accumulates, the profile and natural course of complications are increasingly described. We aim to summarise the available literature on IPC-related complications and the evidence to support specific strategies. PMID- 26870386 TI - Comparative effects of long-acting and short-acting loop diuretics on cardiac sympathetic nerve activity in patients with chronic heart failure. AB - OBJECTIVE: Short-acting loop diuretics are known to enhance cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). The effects of two loop diuretics-long-acting azosemide and short-acting furosemide-on CSNA were evaluated using (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with CHF. METHODS: The present study was a subanalysis of our previously published study, which had reported that serial (123)I-MIBG studies were the most useful prognostic indicator in patients with CHF. Patients with CHF (n=208, left ventricular ejection fraction <45%) but no history of cardiac events for at least 5 months prior to the study were identified according to their histories of acute decompensated heart failure requiring hospitalisation. Patients underwent (123)I MIBG scintigraphy immediately before hospital discharge and at a 6-month follow up. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio and washout rate (WR) were determined using (123)I-MIBG scintigraphy. A total of 108 patients were selected, and propensity score matching was used to compare patients treated with either oral azosemide (n=54) or furosemide (n=54). RESULTS: After treatment, (123)I-MIBG scintigraphic parameters improved in both groups. However, the degree of change in % denervation was -13.8+/-10.5 in the azosemide group and -5.7+/-12.7 in the furosemide group (p<0.01), the change in H/M ratio was 0.20+/-0.16 in the azosemide group and 0.06+/-0.19 in the furosemide group (p<0.01), and the change in WR was -11.3+/-9.2% in the azosemide group and -3.0+/ 12.7% in the furosemide group (p<0.01). Moreover, multivariate analysis showed an independent and significant positive relationship between furosemide and delta-WR from hospital discharge to 6 months after treatment in patients with CHF (p=0.001). CONCLUSIONS: These findings indicate that azosemide suppresses CSNA compared with furosemide in patients with CHF. TRIAL REGISTRATION NUMBER: UMIN000000626 (UMIN-CTR Clinical Trial). PMID- 26870387 TI - Clinical, ECG and echocardiographic clues to the diagnosis of TTR-related cardiomyopathy. AB - BACKGROUND: Signs of cardiac transthyretin (TTR) amyloidosis (ATTR) in patients with echocardiographic increase in interventricular septal thickness (IVST) are lacking. OBJECTIVES: To identify clinical and ECG/echocardiographic signs associated with increased IVST in ATTR. METHODS: Analysis of patients with baseline echocardiography in the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry (N=1682). Patients were categorised into IVST classes according to the American Society of Echocardiography classification adapted to gender (ie, normal, mild, moderate, severe); then into two combined IVST classes (normal-mild and moderate-severe). RESULTS: 425 patients were included: 336 with a TTR mutation (m-TTR) and 89 with wild-type TTR (WT-TTR). 72% were men. Median (25th, 75th centile) age was 62 (45, 72) years. Non-Val30Met and WT-TTR were frequent in moderate (41% and 35%) and severe (50% and 33%) IVST classes. Median IVST was 15 mm (14, 16) (moderate) and 20 mm (18, 22) (severe). In the combined moderate severe class, 85% of patients were >=55 years of age; 81% were men; 86% had blood pressure <140 mm Hg; and 77% had increased right ventricle thickness (>=7 mm). Up to 66% of patients had cardiac sparkling. Systolic dysfunction (left ventricular ejection fraction <50%), restrictive pattern and low voltage were less frequent, and observed in 49%, 18% and 33% of patients, respectively. CONCLUSIONS: Increased IVST, especially in men >=55 years with normal systolic blood pressure, increase in right ventricle free wall and valve thicknesses, and sparkling, should alert practitioners to the possibility of ATTR. Absence of restrictive pattern and low voltage should not rule out the suspicion. TRIAL REGISTRATION NUMBER: NCT00628745 (clinicaltrials.gov). PMID- 26870388 TI - Stress-coping skills and neuroticism in apical ballooning syndrome (Takotsubo/stress cardiomyopathy). AB - INTRODUCTION: Apical ballooning syndrome (ABS) is typically associated with an antecedent stressful situation. Affected patients have been reported to have higher frequencies of premorbid affective disorders. We hypothesised that patients with ABS would have elevated levels of neuroticism (tendency to experience negative affect) and greater vulnerability to stress. METHODS: In this cross-sectional study, all active participants in the Mayo Clinic ABS prospective follow-up registry were invited to complete the third edition of the NEO Personality Inventory (NEO-PI-3). The NEO-PI-3 is the universally accepted measure of the 'Five-Factor Model' of personality. Inventory responses were scored using the NEO-PI-3 computer program and the data were compared with US normative sample used in standardisation of the inventory. Significance was set at 0.0014 to account for multiple comparisons. RESULTS: Of 106 registry participants approached, 53 completed the inventory. There was no difference in age, gender, time from ABS diagnosis, type of antecedent stressor (emotional, physical or none) or severity of initial illness between the responders and non responders. Responders had mean Neuroticism T-scores of 48.0+/-10.6 (95% CI 45.1 to 50.9); p=0.18, when compared with the normal mean of 50. There was also no significant difference in the facet scale of Vulnerability: 46.9+/-8.4 (44.6 to 49.2), p=0.038, at alpha=0.0014. CONCLUSIONS: Contrary to our hypothesis, patients with ABS do not manifest higher levels of neuroticism and do not have greater vulnerability to stress than the general population. These findings have implications for the clinicians' perception of, and approach to, patients with ABS. PMID- 26870390 TI - Does the timing of cardiac rehabilitation impact fitness outcomes? An observational analysis. AB - OBJECTIVES: To ascertain the characteristics associated with delayed cardiac rehabilitation (CR) and determine if an association between CR timing and fitness outcomes exists in patients receiving routine care. METHODS: The study used data from the UK National Audit of Cardiac Rehabilitation, a data set which captures information on routine CR practice and patient outcomes. Data from 1 January 2012 to 8 September 2015 were included. Logistic regression models were used to explore the relationship between timing of CR and fitness-related outcomes as measured by patient-reported exercise level (150 min/week: yes/no), Dartmouth quality of life physical fitness scale and the incremental shuttle-walk test. RESULTS: Based on UK data current CR practice shows that programmes do not always adhere to recommendations on the start of prompt CR, that is, start CR within 28 days of referral (42 days for coronary artery bypass graft (CABG)). Wait time exceeded recommendations in postmyocardial infarction (post-MI), elective percutaneous coronary intervention (PCI), MI-PCI and post-CABG surgery patients. This was particularly pronounced in the medically managed post-MI group, median wait time 40 days. Furthermore, statistical analysis revealed that delayed CR significantly impacts fitness outcomes. For every 1-day increase in CR wait time, patients were 1% less likely to improve across all fitness-related measures (p<0.05). CONCLUSIONS: With the potential for suboptimal patient outcome if starting CR is delayed, efforts should be made to identify and overcome barriers to timely CR provision. PMID- 26870391 TI - Systemic lupus erythematosus and primary fibromyalgia can be distinguished by testing for cell-bound complement activation products. AB - OBJECTIVE: We sought to establish the performance of cell-bound complement activation products (CB-CAPs) as a diagnostic tool to distinguish primary fibromyalgia (FM) from systemic lupus erythematosus (SLE). METHODS: A total of 75 SLE and 75 primary FM adult subjects who fulfilled appropriate classification criteria were enrolled prospectively. CB-CAPs (erythrocyte-C4d (EC4d) and B lymphocyte-C4d (BC4d)) were determined by flow cytometry. Antinuclear antibodies (ANAs) were determined using indirect immunofluorescence while other autoantibodies were determined by solid-phase assays. The CB-CAPs in a multi analyte assay with algorithm (MAAA) relied on two consecutive tiers of analysis that was reported as an overall positive or negative assessment. Test performance was assessed using sensitivity, specificity, positive and negative likelihood ratio (LR). RESULTS: ANAs yielded 80% positives for SLE and 33% positives for FM. High CB-CAP expression (EC4d >14 units or BC4d >60 units) was 43% sensitive and 96% specific for SLE. The CB-CAPs in MAAA assessment was evaluable in 138 of the 150 subjects enrolled (92%) and yielded 60% sensitivity (CI 95% 48% to 72%) for SLE with no FM patient testing positive (100% specificity). A positive test result was associated with a strong positive LR for SLE (>24, CI 95%; 6 to 102), while a negative test result was associated with a moderate negative LR (0.40; CI 95% 0.30 to 0.54). CONCLUSION: Our data indicate that CB-CAPs in MAAA can distinguish FM from SLE. PMID- 26870389 TI - Pentoxifylline for vascular health: a brief review of the literature. AB - Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti inflammatory effects on neutrophils and macrophage/monocytes-some of them attributable to pentoxifylline metabolites-appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable. PMID- 26870392 TI - Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. AB - The global development of a biosimilar product is a methodologically complex affair, lined with potential design pitfalls and operational missteps to be avoided. Without careful attention to experimental design and meticulous execution, a development programme may fail to demonstrate equivalence, as would be anticipated for a biosimilar product, and not receive regulatory approval based on current guidance. In order to demonstrate similarity of a biosimilar product versus the originator (ie, the branded product), based on regulatory guidance, a stepwise approach is usually taken, starting with a comprehensive structural and functional characterisation of the new biological moiety. Given the sequential nature of the review process, the extent and nature of the non clinical in vivo studies and the clinical studies to be performed depend on the level of evidence obtained in these previous step(s). A clinical efficacy trial is often required to further demonstrate biosimilarity of the two products (biosimilar vs branded) in terms of comparative safety and effectiveness. Owing to the focus on demonstrating biosimilarity and not safety and efficacy de novo, designing an adequate phase III (potentially pivotal) clinical efficacy study of a biosimilar may present some unique challenges. Using adalimumab as an example, we highlight design elements that may deserve special attention. PMID- 26870393 TI - Social Role Participation Questionnaire for patients with ankylosing spondylitis: translation into Dutch, reliability and construct validity. AB - OBJECTIVE: The Social Role Participation Questionnaire (SRPQ) assesses the influence of health on participation in 11 specific and one general participation role across 4 participation dimensions: 'importance', 'satisfaction with time', 'satisfaction with performance' and 'physical difficulty'. This study aimed to translate the SRPQ into Dutch, and assess the clinimetric properties and aspects of its validity among patients with ankylosing spondylitis (AS). METHODS: Translation was performed using the dual panel approach. For each participation dimension, internal consistency, test-retest reliability (n=31), and construct validity were assessed in 246 patients with AS. RESULTS: The translation required only minor adaptations. Cronbach alphas were alpha>=0.7. A strong correlation was present between satisfaction with 'time' and 'performance'(r=0.85). Test-retest reliability was satisfactory (kappa=0.79-0.95). Correlations with participation domains of the Short-Form Health Survey 36 (SF-36), the WHO Disease Assessment Score II, and generic as well as disease-specific health outcomes (Physical and Mental component scale of the SF-36, Satisfaction With Life Scale, Bath Ankylosing Spondylitis Disease Index (BASDAI), Bath Ankylosing Spondylitis Functioning Index (BASFI)) were at least moderate (r=-0.41 to 0.75) for all dimensions except for 'role importance' where correlations were weak (r<=40). Discriminative ability across 5 self-reported health states was good for all dimensions (p<0.01). The 'general participation' role showed similar reliability and validity for each dimension, as the average of the all 11 roles. CONCLUSIONS: The Dutch version of the SRPQ is available to help understand social role participation of patients with AS. The dimension 'role importance' measures a distinct aspect of participation. The general participation item was a good global measure of participation. PMID- 26870394 TI - Factors associated with a bad functional prognosis in early inflammatory back pain: results from the DESIR cohort. AB - BACKGROUND: Spondyloarthritis (SpA) is a heterogeneous disease with hardly predictable potential courses. We aimed at determining prognostic factors of bad functional outcome at 2 years in patients with early inflammatory back pain (IBP). METHODS: Data from patients included in the French multicentre devenir des spondylarthropathies indifferenciees recentes (DESIR) cohort, that is, suffering from IBP starting before 50 years of age and lasting for 3-36 months, were used. A bad functional outcome at 24 months was defined as an increase in bath ankylosing spondylitis functional index (BASFI), or BASFI at 2 years higher than the 75th centile in the cohort. Demographic, clinical, biological and radiological data collected at inclusion were compared in patients with bad functional outcome versus others, by chi(2) test, then by a multivariate logistic regression model with stepwise selection of relevant factors. RESULTS: 513 patients (54.4% females, 72.2% fulfilling ASAS criteria) were assessed. Of those, 130 (25.3%) fulfilled the aforementioned criteria of a bad functional outcome (BASFI increase >=4 units or >=36 at 2 years). Multivariate analysis revealed that not fulfilling ASAS criteria, female sex, age >33 years, lower educational level, active smoking status and high disease activity according to bath ankylosing spondylitis disease activity index (BASDAI) at baseline were independently associated with a bad functional outcome at 24 months. Sensitivity analyses restricted to patients fulfilling ASAS criteria for SpA resulted in similar results. CONCLUSION: We observed, in a large prospective cohort of patients with early IBP, formerly described bad prognostic factors, especially a low educational level, an older age and a high disease activity at onset, and revealed that active smoking status and female sex were also independently associated with a poor outcome. Fulfilment of ASAS criteria, on the other hand, was predictive of a better outcome, most likely due to the more consensual management of a defined disease. PMID- 26870395 TI - Crystal structure of bis-p-anizidinegossypol with an unknown solvate. AB - The title compound, C44H44N2O8, (systematic name: 1,1',6,6'-tetra-hydroxy-5,5' diisopropyl-8,8'-bis-{[(4-meth-oxy-phen-yl)iminium-yl]meth-yl}-3,3'-dimethyl-2,2' bi-naphthalene-7,7'-diolate) has been obtained by the addition of p-anizidine to gossypol dissolved in di-chloro-methane. In the solid state, the title compound exists in the enamine or quinoid form. The two naphthyl moieties are inclined to one another by 72.08 (5) degrees . The pendant phenyl rings are inclined at 22.26 (14) and 23.86 (13) degrees to the corresponding naphthyl rings. In the crystal, mol-ecules are incorporated into layers through inversion-related pairs of O-H?O inter-actions [graph sets R 2 (2)(20) and R 2 (2)(10)] and translation-related O H?O inter-actions [graph set C(15)]. The packing of these layers in the crystal structure gives rise to channels in the [011] direction, with hydro-phobic inter actions occurring between adjacent layers. The channels are 5-7 A wide, and the void volume of each cell is 655 A(3), corresponding to 26.6% of the cell volume. Disordered guest mol-ecules, probably solvent and water mol-ecules, occupy these voids of the crystal; their contribution to the scattering was removed with the SQUEEZE routine [Spek (2015 ?). Acta Cryst. C71, 9-18] of PLATON [Spek (2009 ?). Acta Cryst. D65, 148-155]. PMID- 26870396 TI - Crystal structure and computational study of 3,4-dihy-droxy-3-hy-droxy-methyl-9 methyl-6-methyl-idene-3a,4,5,6,6a,9,9a,9b-octa-hydro-azuleno[4,5-b]furan 2,8(3H,7H)-dione. AB - In the mol-ecule of title compound, C15H20O6, also known as cynarinin A, the cyclo-pentane ring having twist conformation and a gamma-lactone ring assuming an envelope conformation are trans- and cis-fused, respectively, to a cyclo-heptane ring adopting a twist-chair conformation. In the crystal, O-H?O hydrogen bonds link neighbouring mol-ecules, forming a three-dimensional network. Theoretical calculations of the mol-ecular structure using the CNDO approximation and MOPAC PM3 geometry optimization are in satisfactory agreement with the results of the X ray structure analysis. PMID- 26870397 TI - Crystal structure of 1,3-bis-(2,3-di-methyl-quinoxalin-6-yl)benzene. AB - The title compound, C26H22N4 (I), was synthesized by C-H iridium-catalyzed borylation followed by Suzuki coupling. The mol-ecular structure of (I) consists of a central benzene ring with 3-di-methyl-quinoxalin-6-yl groups at the 1 and 3 positions. These 2,3-di-methyl-quinoxalin-6-yl groups twist significantly out of the plane of the benzene ring. There are inter-molecular pi-pi inter-actions which result in a two-dimensional extended structure. The layers extend parallel to the ab plane and stack along the c axis. PMID- 26870398 TI - Crystal structure of 2-{[(E)-(4-anilinophen-yl)iminium-yl]meth-yl}-5-(di-ethyl amino)-phenolate. AB - The title compound, C23H25N3O, crystallized with one single mol-ecule in the asymmetric unit and is present in the zwitterionic form. There is an intra molecular N-H?O hydrogen bond in the mol-ecule with the phenol ring being inclined to the central benzene ring by 20.67 (14) degrees . The terminal amino phenyl ring forms a dihedral angle of 54.21 (14) degrees with the central benzene ring. The two outer aromatic rings are inclined to one another by 74.54 (14) degrees . In the crystal, the mol-ecules are connected by N-H?O hydrogen bonds, with adjacent molecules related by a 21 screw axis, generating -A-B-A-B- zigzag chains extending along [010]. The chains are linked via C-H?pi and pi-pi inter-actions [with a centroid-centroid distance of 3.444 (3) A] between the benzene ring and the imino group of symmetry-related mol-ecules, forming slabs lying parallel to (100). PMID- 26870399 TI - Crystal structure of hydrazine iron(III) phosphate, the first transition metal phosphate containing hydrazine. AB - The title compound, poly[(MU2-hydrazine)(MU4-phosphato)iron(III)], [Fe(PO4)(N2H4)] n , was prepared under hydro-thermal conditions. Its asymmetric unit contains one Fe(III) atom located on an inversion centre, one P atom located on a twofold rotation axis, and two O, one N and two H atoms located on general positions. The Fe(III) atom is bound to four O atoms of symmetry-related PO4 tetra-hedra and to two N atoms of two symmetry-related hydrazine ligands, resulting in a slightly distorted FeO4N2 octa-hedron. The crystal structure consists of a three-dimensional hydrazine/iron phoshate framework whereby each PO4 tetra-hedron bridges four Fe(III) atoms and each hydrazine ligand bridges two Fe(III) atoms. The H atoms of the hydrazine ligands are also involved in moderate N-H?O hydrogen bonding with phosphate O atoms. The crystal structure is isotypic with the sulfates [Co(SO4)(N2H4)] and [Mn(SO4)(N2H4)]. PMID- 26870400 TI - Crystal structure of 2,2''-bis-(2,7-di-chloro-9-hy-droxy-9H-fluoren-9-yl) 1,1':4',1''-terphenyl tri-ethyl-amine trisolvate. AB - In the title solvate, C44H26Cl4O2.3C6H15N, the asymmetric part of the unit cell comprises two halves of the diol mol-ecules, 2,2''-bis-(2,7-di-chloro-9-hy-droxy 9H-fluoren-9-yl)-1,1':4',1''-terphenyl, and three mol-ecules of tri-ethyl-amine, i. e. the diol mol-ecules are located on crystallographic symmetry centres. Two of the solvent mol-ecules are disordered over two positions [occupancy ratios of 0.567 (3):0.433 (3) and 0.503 (3):0.497 (3)]. In the diol mol-ecules, the outer rings of the 1,1':4',1''-terphenyl elements are twisted with reference to their central arene ring and the mean planes of the fluorenyl moieties are inclined with respect to the terphenyl ring to which they are connected, the latter making dihedral angles of 82.05 (8) and 82.28 (8) degrees . The presence of two 9 fluoren-9-ol units attached at positions 2 and 2'' of the terphenyl moiety induces a 'folded' geometry which is stabilized by intra-molecular C-H?O hydrogen bonds and pi-pi stacking inter-actions, the latter formed between the fluorenyl units and the central ring of the terphenyl unit [centroid-centroid distances = 3.559 (1) and 3.562 (1) A]. The crystal is composed of 1:2 complex units, in which the solvent mol-ecules are associated with the diol mol-ecules via O-H?N hydrogen bonds, while the remaining solvent mol-ecule is linked to the host by a C-H?N hydrogen bond. The given pattern of inter-molecular inter-actions results in formation of chain structures extending along [010]. PMID- 26870401 TI - Crystal structure of tris-(piperidinium) hydrogen sulfate sulfate. AB - In the title molecular salt, 3C5H12N(+).HSO4 (-).SO4 (2-), each cation adopts a chair conformation. In the crystal, the hydrogen sulfate ion is connected to the sulfate ion by a strong O-H?O hydrogen bond. The packing also features a number of N-H?O hydrogen bonds, which lead to a three-dimensional network structure. The hydrogen sulfate anion accepts four hydrogen bonds from two cations, whereas the sulfate ion, as an acceptor, binds to five separate piperidinium cations, forming seven hydrogen bonds. PMID- 26870402 TI - Crystal structures of bis- and hexakis[(6,6'-di-hydroxy-bipyridine)copper(II)] nitrate coordination complexes. AB - Two multinuclear complexes synthesized from Cu(NO3)2 and 6,6'-di-hydroxy bipyridine (dhbp) exhibit bridging nitrate and hydroxide ligands. The dinuclear complex (6,6'-di-hydroxy-bipyridine-2kappa(2) N,N')[MU-6-(6-hy-droxy-pyridin-2 yl)pyridin-2-olato-1:2kappa(3) N,N':O (2)](MU-hydroxido-1:2kappa(2) O:O')(MU nitrato-1:2kappa(2) O:O')(nitrato-1kappaO)dicopper(II), [Cu2(C10H7N2O2)(OH)(NO3)2(C10H8N2O2)] or [Cu(6-OH-6'-O-bpy)(NO3)(MU-OH)(MU NO3)Cu(6,6'-dhbp)], (I), with a 2:1 ratio of nitrate to hydroxide anions and one partially deprotonated dhbp ligand, forms from a water-ethanol mixture at neutral pH. The hexa-nuclear complex bis-(MU3-bi-pyridine-2,2'-diolato-kappa(3) O:N,N':O')tetra-kis-(6,6'-di-hydroxy-bipyridine-kappa(2) N,N')tetra-kis-(MU hydroxido-kappa(2) O:O')bis-(methanol-kappaO)tetra-kis-(MU-nitrato-kappa(2) O:O')hexa-copper(II), [Cu6(C10H6N2O2)2(CH4O)2(OH)4(NO3)4(C10H8N2O2)4] or [Cu(6,6' dhbp)(MU-NO3)2(MU-OH)Cu(6,6'-O-bpy)(MU-OH)Cu(6,6'dhbp)(CH3OH)]2, (II), with a 1:1 NO3-OH ratio and two fully protonated and fully deprotonated dhbp ligands, was obtained by methanol recrystallization of material obtained at pH 3. Complex (II) lies across an inversion center. Complexes (I) and (II) both display intra molecular O-H?O hydrogen bonding. Inter-molecular O-H?O hydrogen bonding links symmetry-related mol-ecules forming chains along [100] for complex (I) with pi stacking along [010] and [001]. Complex (II) forms inter-molecular O-H?O hydrogen bonded chains along [010] with pi-stacking along [100] and [001]. PMID- 26870403 TI - Crystal structure of 4,4'-di-bromo-2',5'-dimeth-oxy-[1,1'-biphen-yl]-2,5-dione (BrHBQBr). AB - In the title compound, C14H10Br2O4, the dihedral angle between the aromatic rings is 67.29 (19) degrees . Both meth-oxy-group C atoms lie close to the plane of their attached ring [deviations = -0.130 (4) and 0.005 (5) A]. In the crystal, mol-ecules pack in a centrosymmetric fashion and inter-act via a mixture of weak pi-pi stacking inter-actions [centroid-centoid separations = 4.044 (2) and 4.063 (3) A], weak C-H?O hydrogen bonding, and Br?Br halogen bonding. This induces a geometry quite different than that predicted by theory. PMID- 26870404 TI - Crystal structures of two erbium(III) complexes with 4-amino-benzoic acid and 4 chloro-3-nitro-benzoic acid. AB - The crystal structures of two erbium(III) complexes with 4-amino-benzoic acid (4 ABAH), namely bis-(MU2-4-amino-benzoato-kappa(2) O:O')bis-[bis(4-amino-benzoato kappa(2) O,O')di-aqua-erbium(III)] dihydrate, [Er2(C7H6NO2)6(H2O)4].2H2O, (I), and 4-chloro-3-nitro-benzoic acid (CLNBAH), namely poly[hexa-kis-(MU2-4-chloro-3 nitro-benzoato-kappa(2) O:O')bis-(dimethyl sulfoxide-kappaO)dierbium(III)], [Er2(C7H3ClNO4)6(C2H6OS)2] n , (II), have been determined. In the structure of solvatomorphic compound (I), the symmetry-related irregular ErO8 coordination polyhedra in the discrete centrosymmetric dinuclear complex comprise two monodentate water mol-ecules and six carboxyl-ate O-atom donors, four from two bidentate carboxyl-ate O,O'-chelate groups and two from the bis-monodentate O:O' bridging group of the third 4-ABA anion. The Er-O bond-length range is 2.232 (3) 2.478 (3) A and the Er?Er separation in the dinuclear complex unit is 4.7527 (4) A. One of the coordinating water mol-ecules is involved in an intra-unit O-H?O hydrogen-bonding association with an inversion-related carboxyl-ate O-atom acceptor. In contrast, the anhydrous compound (II) is polymeric, based on centrosymmetric dinuclear repeat units comprising ErO7 coordination polyhedra which involve four O-atom donors from two bidentate O:O'-bridging carboxyl-ate groups, one O-atom donor from the monodentate dimethyl sulfoxide ligand and two O atom donors from the third bridging CLNBA anion. The latter provides the inter unit link in the one-dimensional coordination polymer extending along [100]. The Er-O bond-length range in (II) is 2.239 (6)-2.348 (6) A and the Er?Er separation within the dinuclear unit is 4.4620 (6) A. In the crystal of (I), extensive inter dimer O-H?O and N-H?O hydrogen-bonding inter-actions involving both the coordinating water mol-ecules and the solvent water mol-ecules, as well as the amine groups of the 4-ABA anions, give an overall three-dimensional network structure. Within this structure are also weak pi-pi ring inter-actions between two of the coordinating ligands [ring-centroid separations = 3.676 (3) and 3.711 (2) A]. With (II), only weak intra-polymer C-H?O, C-H?Cl and C-H?S inter-actions are present. PMID- 26870405 TI - Crystal structures of three mercury(II) complexes [HgCl2 L] where L is a bidentate chiral imine ligand. AB - The crystal structures of three complexes [HgCl2 L] were determined, namely, (S) (+)-di-chlorido-[1-phenyl-N-(pyridin-2-yl-methyl-idene)ethyl-amine-kappa(2) N,N']mercury(II), [HgCl2(C14H14N2)], (S)-(+)-di-chlorido-[1-(4-methyl-phen-yl)-N (pyridin-2-yl-methyl-idene)ethyl-amine-kappa(2) N,N']mercury(II), [HgCl2(C15H16N2)], and (1S,2S,3S,5R)-(+)-di-chlorido-[N-(pyridin-2-yl-methyl idene)isopino-camph-eyl-amine-kappa(2) N,N']mercury(II), [HgCl2(C16H22N2)]. The complexes consist of a bidentate chiral imine ligand coordinating to HgCl2 and crystallize with four independent mol-ecules in the first complex and two independent mol-ecules in the other two. The coordination geometry of mercury is tetra-hedral, with strong distortion towards a disphenoidal geometry, as a consequence of the imine bite angle being close to 70 degrees . The Cl-Hg-Cl angles span a large range, 116.0 (2)-138.3 (3) degrees , which is related to the aggregation state in the crystals. For small Cl-Hg-Cl angles, complexes have a tendency to form dimers, via inter-molecular Hg?Cl contacts. These contacts become less significant in the third complex, which features the largest intra molecular Cl-Hg-Cl angles. PMID- 26870406 TI - Crystal structure of di-MU-aqua-MU-(pyrazine N,N'-dioxide)-kappa(2) O:O-bis-(di aqua-sodium) tetra-phenyl-borate dihydrate pyrazine N,N'-dioxide monosolvate. AB - The search for novel lanthanide coordination networks using pyrazine N,N'-dioxide (pzdo, C4H4N2O2) as a structure-directing unit, led to the synthesis and the structure determination of the title compound, [Na2(C4H4N2O2)(H2O)6][B(C6H5)4]2.C4H4N2O2.2H2O. The crystal structure is comprised of discrete [{Na(H2O)2}2(MU-H2O)2(MU-pzdo)](2+) cations and tetra phenyl-borate anions, as well as pzdo and H2O solvent mol-ecules. The dinuclear cation is located about a twofold rotation axis, and the symmetry-related Na(I) atoms display a distorted square-pyramidal coordination sphere defined by two O atoms of terminal water ligands, two O atoms of bridging water ligands and one O atom of a bridging pzdo ligand. In the crystal, O-H?O hydrogen bonds link the dinuclear cation and solvent pzdo mol-ecules (point-group symmetry -1) into rectangular grid-like layers parallel to the bc plane. Additional C-H?O, O-H?O, C H?pi and O-H?pi inter-actions link the anion and solvent water mol-ecules to the layers. The layers are further linked into a three-dimensional network through a combination of C-H?pi and O-H?pi hydrogen bonds involving the tetra-phenyl-borate anion. PMID- 26870407 TI - Crystal structure of (2',3,6'-tri-chloro-biphenyl-2-yl)boronic acid tetra-hydro furan monosolvate. AB - The title compound, C12H8BCl3O2.C4H8O, crystallizes as a tetra-hydro-furan monosolvate. The boronic acid group adopts a syn-anti conformation and is significantly twisted along the carbon-boron bond by 69.2 (1) degrees , due to considerable steric hindrance from the 2',6'-di-chloro-phenyl group that is located ortho to the boronic acid substituent. The phenyl rings of the biphenyl are almost perpendicular to one another, with a dihedral angle of 87.9 (1) degrees between them. In the crystal, adjacent mol-ecules are linked via O-H?O inter-actions to form centrosymmetric dimers with R 2 (2)(8) motifs, which have recently been shown to be energetically very favourable. The hy-droxy groups are in an anti conformation and are also engaged in hydrogen-bonding inter-actions with the O atom of the tetra-hydro-furan solvent mol-ecule. Cl?Cl halogen-bonding inter-actions [Cl?Cl = 3.464 (1) A] link neigbouring dimers into chains running along [010]. Further aggregation occurs due to an additional Cl?Cl halogen bond [Cl?Cl = 3.387 (1) A]. PMID- 26870408 TI - Crystal structure of 9,10-bis-(1,3-di-thiol-2-yl-idene)-9,10-di-hydro-anthracene. AB - The crystal structure of the well-studied 9,10-bis-(1,3-di-thiol-2-yl-idene)-9,10 di-hydro-anthracene mol-ecule, C20H12S4, (I), also known as exTTF, is reported. The mol-ecular structure of (I) consists of a di-hydro-anthracene moiety with two 1,3-di-thiol-2-yl-idene substituents. This is a saddle-shaped mol-ecule, which inter-acts with a close neighbor through various pi-pi and C-H?pi contacts to form a 'dimer'. These 'dimers' inter-act through a series of C-H?S and C-H?pi contacts to construct a complex three-dimensional extended structure. PMID- 26870409 TI - The crystal structures of tetra-kis-(MU-n-butyrato-kappa(2) O:O')bis[bromidorhenium(III)] and tetra-kis-(MU-n-butyrato-kappa(2) O:O')bis[chlorido-rhenium(III)] aceto-nitrile disolvate. AB - The title complexes, [Re2Br2(O2CC3H7)4], (1), and [Re2(O2CC3H7)4Cl2].2CH3CN, (2), both exhibit paddlewheel structures with four carboxyl-ate ligands bridging two Re(III) atoms. The Re-Re distances are 2.2325 (2) and 2.2299 (3) A, indicating quadruple bonds between the Re(III) atoms in each complex. Both complexes contain an inversion center at the mid-point of the Re-Re bond. The Re-Br bond [2.6712 (3) A] in (1) is 0.1656 (6) A longer than the Re-Cl distance [2.5056 (5) A] of (2). In (2), the N atom of each co-crystallized aceto-nitrile solvent mol-ecule is nearly equidistant between and in close contact with two carboxyl-ate C atoms. PMID- 26870410 TI - Crystal structure of {6,6'-dibenzoyl-4,4'-di-tert-butyl-2,2'-[(ethane-1,2-di yl)di-nitrilo-bis-(phenyl-methanylyl-idene)]diphenolato-kappa(4) O (1),N,N',O (1')}nickel(II). AB - The mononuclear title complex, [Ni(C50H46N2O4)], crystallizes in the triclinic space group P-1, with two mol-ecules in the asymmetric unit (Z' = 2). Each Ni(II) atom has a slightly distorted square-planar geometry [omega = 3.91 (5) degrees and 2.04 (7) degrees ] defined by the two phenolate O and two imine N atoms of the tetra-dentate Schiff base ligand. The dihedral angles between the central phenolate ring and peripheral phenyl rings are 60.5 (2)/70.0 (2) and 86.4 (2)/56.1 (2) degrees in mol-ecule A, and 89.43 (19)/18.0 (2) and 63.87 (19)/68.2 (2) degrees in mol-ecule B. The two central phenolate rings are twisted by angles of 19.37 (19) and 19.36 (18) degrees in the two mol-ecules. The packing is stabilized through intra- and inter-molecular C-H?O and C-H?pi inter-actions, forming chains parallel to the b axis. The tert-butyl groups in one of the two mol-ecules are positionally disordered with a refined occupancy ratio of 0.707 (13):0.293 (13). PMID- 26870411 TI - Crystal structures of 3,5-bis-[(E)-3-hy-droxy-benzyl-idene]-1-methyl-piperidin-4 one and 3,5-bis-[(E)-2-chloro-benzyl-idene]-1-methyl-piperidin-4-one. AB - The title compounds, C20H19NO3, (1), and C20H17Cl2NO, (2), are the 3-hy-droxy benzyl-idene and 2-chloro-benzyl-idene derivatives, respectively, of curcumin [systematic name: (1E,6E)-1,7-bis-(4-hy-droxy-3-meth-oxy-phen-yl)-1,6-hepta-diene 3,5-dione]. The dihedral angles between the benzene rings in each compound are 21.07 (6) degrees for (1) and 13.4 (3) degrees for (2). In both compounds, the piperidinone rings adopt a sofa confirmation and the methyl group attached to the N atom is in an equatorial position. In the crystal of (1), two pairs of O-H?N and O-H?O hydrogen bonds link the mol-ecules, forming chains along [10-1]. The chains are linked via C-H?O hydrogen bonds, forming undulating sheets parallel to the ac plane. In the crystal of (2), mol-ecules are linked by weak C-H?Cl hydrogen bonds, forming chains along the [204] direction. The chains are linked along the a-axis direction by pi-pi inter-actions [inter-centroid distance = 3.779 (4) A]. For compound (2), the crystal studied was a non-merohedral twin with the refined ratio of the twin components being 0.116 (6):0.886 (6). PMID- 26870412 TI - Crystal structure of di-chlorido-bis-(1,3-diazinane-2-thione-kappaS)cadmium. AB - In the structure of the title compound, [CdCl2(C4H8N2S)2], the Cd(II) atom is coordinated by two chloride ions and two 1,3-diazinane-2-thione (Diaz) mol-ecules through their S atoms. The geometry around the Cd(II) atom is distorted tetra hedral, with bond angles in the range 101.55 (7)-117.91 (8) degrees . The CH2 groups of one Diaz ligand are disordered over two sets of sites with an occupancy ratio of 0.711 (12):0.289 (12). The mol-ecular structure is stabilized by intra molecular N-H?Cl hydrogen-bonding inter-actions, generating a butterfly syn conformation. Inter-molecular N-H?Cl and N-H?S inter-actions lead to the formation of a three-dimensional network structure. The structure has been determined from a crystal twinned by nonmerohedry, by a 180 degrees rotation around the reciprocal c axis. The twin ratio refined to 0.8866 (6):0.1134 (6). PMID- 26870413 TI - Crystal structure of nitridobis(tri-methyl-silanolato)[1,1,1-trimethyl-N-(tri methyl-sil-yl)silanaminato]molybdenum(VI). AB - In the title compound, [Mo(C6H18NSi2)(C3H9OSi)2N], the Mo(VI) cation is located on a mirror plane and is coordinated by a nitride anion, a 1,1,1-trimethyl-N-(tri methyl-sil-yl)silanaminate anion and two tri-methyl-silanolate anions in a distorted tetra-hedral geometry; the N atom and two Si atoms of the 1,1,1 trimethyl-N-(tri-methyl-sil-yl)silanaminato anionic ligand are also located on the mirror plane. The Mo N bond length of 1.633 (6) A is much shorter than the Mo N single-bond length of 1.934 (7) A. No hydrogen bonding is observed in the crystal structure. PMID- 26870414 TI - Crystal structure of N-(2,2,2-tri-chloro-1-hy-droxy-eth-yl)formamide. AB - The title compound, C3H4Cl3NO2, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The two mol-ecules have the same conformation; the mol-ecular overlap gives weighted and unit-weight r.m.s. fits of 0.047 and 0.043 A, respectively. The conformation of the N-(hydroxeth-yl)formamide chains are very similar, as indicated by the C-N(H)-C=O and C-N(H)-C-O(H) torsion angles, which are, respectively, -1.8 (3) and -91.5 (2) degrees for mol-ecule A, and 2.1 (3) and -95.7 (2) degrees for mol-ecule B. In the crystal, individual mol ecules are linked by pairs of O-H?O hydrogen bonds, forming A-A and B-B inversion dimers with R 2 (2)(12) ring motifs. The dimers are linked via N-H?O hydrogen bonds, forming alternating layers of A and B mol-ecules parallel to the bc plane. Within the layers of B mol-ecules, there are weak C-H?Cl hydrogen bonds present. PMID- 26870415 TI - Crystal structures of two bis-(iodo-meth-yl)benzene derivatives: similarities and differences in the crystal packing. AB - The isomeric derivatives 1,2-bis-(iodo-meth-yl)benzene, (I), and 1,3-bis-(iodo meth-yl)benzene (II), both C8H8I2, were prepared by metathesis from their di bromo analogues. The ortho-derivative, (I), lies about a crystallographic twofold axis that bis-ects the C-C bond between the two iodo-methyl substituents. The packing in (I) relies solely on C-H?I hydrogen bonds supported by weak parallel slipped pi-pi stacking inter-actions [inter-centroid distance = 4.0569 (11) A, inter-planar distance = 3.3789 (8) A and slippage = 2.245 A]. While C-H?I hydrogen bonds are also found in the packing of (II), type II, I?I halogen bonds [I?I = 3.8662 (2) A] and C-H?pi contacts feature prominently in stabilizing the three-dimensional structure. PMID- 26870416 TI - Crystal structure of 10a-hy-droxy-9-(3-nitro-phen-yl)-3,6-diphenyl 3,4,5,6,7,8a,9,10a-octa-hydro-1H-xanthene-1,8(2H)-dione. AB - In the octa-hydroxanthenedione unit of the title compound, C31H27NO6, the central di-hydro-pyran ring shows an envelope conformation, while the bilateral cyclo hexene and cyclo-hexane rings adopt a half-boat conformation and a chair conformation, respectively. The nitro-benzene ring is twisted with respect to the two benzene rings, making dihedral angles of 63.1 (1) and 63.0 (1) degrees . In the crystal, O-H?O hydrogen bonds link the mol-ecules into supra-molecular chains propagating along the a-axis direction. PMID- 26870417 TI - Crystal structure of (3E,5E)-3,5-bis-[4-(di-ethyl-aza-nium-yl)benzyl-idene]-1 methyl-4-oxopiperidin-1-ium trichloride dihydrate: a potential biophotonic material. AB - In the trication of the title hydrated mol-ecular salt, C28H40N3O(3+).3Cl( ).2H2O, the central heterocyclic ring adopts a sofa conformation, with the exocyclic N-C bond in an equatorial orientation. The dihedral angles between the planar part of this heterocyclic ring and the two almost flat side-chain fragments, which include the aromatic ring and bridging atoms, are 28.8 (1) and 41.1 (1) degrees . Both di-ethyl-aza-niumyl substituents have a tetra-hedral geometry, while the dihedral angles between the above-mentioned flat part of the aryl fragments and the imaginary planes drawn through atoms C-N-C of the di-ethyl aza-niumyl substituents are 86.3 (2) and 80.4 (1) degrees , respectively. In the crystal, N-H?Cl hydrogen bonds link the cations and anions into [100] chains. The chains are cross-linked by numerous C-H?O and C-H?Cl inter-actions, generating a three-dimensional network. One of the chloride ions is disordered over two adjacent positions in a 0.895 (4):0.105 (4) ratio. PMID- 26870418 TI - Crystal structures of two 2,9-di-thia-13-aza-dispiro-[4.1.4(7).3(5)]tetra-decan-6 ones. AB - In the title compounds 4,11-dihy-droxy-13-methyl-1,8-di-p-tolyl-2,9-di-thia-13- aza-dispiro-[4.1.4(7).3(5)]tetra-decan-6-one, C26H31NO3S2, (I), and 13-benzyl 4,11-dihy-droxy-1,8-bis-(4-methyl-phen-yl)-2,9-di-thia-13-aza-dispiro [4.1.4(7).3(5)]tetradecan-6-one, C32H35NO3S2, (II), the piperidine rings adopt distorted chair conformations. The thio-phene rings in (I) have envelope conformations, with the spiro C atoms as the flaps. In (II), one thio-phene ring (D) has an envelope conformation, with the hy-droxy-substituted C atom as the flap, while the other thio-phene ring (E) has a twisted conformation on the C-C bond involving the spiro C atom and the toluyl-substituted C atom. In (I), the mean plane of the piperidine ring makes dihedral angles of 75.16 (9) and 73.33 (8) degrees with the mean planes of the thio-phene rings (D and E), respectively. In (II), the corresponding dihedral angles are 70.95 (11) and 77.43 (12) degrees . In both compounds, there is an intra-molecular O-H?O hydrogen bond forming an S(6) ring motif. In the crystal of (I), mol-ecules are linked via O H?N and C-H?O hydrogen bonds, forming chains along [010]. There are also pi-pi inter-actions present involving inversion-related benzene rings, linking the chains to form slabs parallel to (100). In the crystal of (II), mol-ecules are linked via O-H?O hydrogen bonds, forming inversion dimers with an R 4 (4)(8) ring motif. The dimers are linked by C-H?pi inter-actions, forming slabs parallel to (001). PMID- 26870419 TI - Crystal structure of N-[(1S,2S)-2-amino-cyclo-hex-yl]-2,4,6-tri-methyl-benzene sulfonamide. AB - The title compound, C15H24N2O2S, was synthesized via a substitution reaction between the enanti-opure (1S,2S)-(+)-1,2-di-amino-cyclo-hexane and 2,4,6-tri methyl-benzene-1-sulfonyl chloride. The cyclo-hexyl and phenyl substituents are oriented gauche around the sulfonamide S-N bond. In the crystal, mol-ecules are linked via N-H?N hydrogen bonds, forming chains propagating along [100]. PMID- 26870420 TI - Crystal structure of 4-({(1E,2E)-3-[3-(4-fluoro-phen-yl)-1-isopropyl-1H-indol-2 yl]allyl-idene}amino)-1H-1,2,4-triazole-5(4H)-thione. AB - The asymmetric unit of the titled compound, C22H20FN5S, comprises two independent mol-ecules (A and B), both of which have a trans conformation with respect to the methene C=C [1.342 (2) and 1.335 (2) A] and the acyclic N=C [1.283 (2) and 1.281 (2) A] bonds. In mol-ecule A, the triazole ring makes dihedral angles of 55.01 (12) and 18.17 (9) degrees with the benzene and indole rings, respectively. The corresponding dihedral angles for mol-ecule B are 54.54 (11) and 14.60 (10) degrees , respectively. In the crystal, mol-ecules are consolidated into -A-B-A-B chains along [010] via N-H?N hydrogen bonds. The chains are further linked into layers parallel to the ac plane via pi-pi inter-actions involving inversion related triazole rings [centroid-centroid distances = 3.3436 (11)-3.4792 (13) A]. PMID- 26870421 TI - Crystal structure of (+/-)-(5SR,6SR)-6-ethenyl-1-[(RS)-1-phenyl-eth-oxy]-1-aza spiro-[4.5]decan-2-one. AB - In the title compound, C19H25NO2, the pyrrolidine ring adopts an envelope form, with the spiro C atom as the flap, while the cyclo-hexane ring shows a chair form. A weak intra-molecular C-H?O inter-action supports the mol-ecular conformation, generating an S(6) ring motif. In the crystal, pairs of C-H?O inter actions connect the mol-ecules into inversion dimers with an R 2 (2)(16) ring motif. The dimers are linked by a second pair of C-H?O inter-actions, enclosing an R 4 (2)(12) ring motif, into a tape structure along the b axis. PMID- 26870422 TI - Crystal structures of tris-[1-oxo-pyridine-2-olato(1-)]silicon(IV) chloride chloro-form-d 1 disolvate, tris-[1-oxo-pyridine-2-olato(1-)]silicon(IV) chloride aceto-nitrile unqu-anti-fied solvate, and fac-tris-[1-oxo-pyridine-2-thiol-ato(1 )]silicon(IV) chloride chloro-form-d 1 disolvate. AB - The cations in the title salts, [Si(OPO)3]Cl.2CDCl3, (I), [Si(OPO)3]Cl.xCH3CN, (II), and fac-[Si(OPTO)3]Cl.2CDCl3, (III) (OPO = 1-oxo-2-pyridin-one, C5H4NO2, and OPTO = 1-oxo-2-pyridine-thione, C5H4NOS), have distorted octa-hedral coordination spheres. The first two structures contain the same cation and anion, but different solvents of crystallization led to different solvates and packing arrangements. In structures (I) and (III), the silicon complex cations and chloride anions are well separated, while in (II), there are two C-H?Cl distances that fall just within the sum of the van der Waals radii of the C and Cl atoms. The pyridine portions of the OPO ligands in (I) and (II) are modeled as disordered with the planar flips of themselves [(I): 0.574 (15):0.426 (15), 0.696 (15):0.304 (15), and 0.621 (15):0.379 (15); (II): 0.555 (13):0.445 (13), 0.604 (14):0.396 (14) and 0.611 (13):0.389 (13)], demonstrating that both fac and mer isomers are co-crystallized. In (II), highly disordered solvent, located in two independent channels along [100], was unable to be modeled. Reflection contributions from this solvent were fixed and added to the calculated structure factors using the SQUEEZE [Spek (2015 ?). Acta Cryst. C71, 9-18] function of program PLATON, which determined there to be 54 electrons in 225 A(3) accounted for per unit cell (25 electrons in 109 A(3) in one channel, and 29 electrons in 115 A(3) in the other). In (I) and (II), all species lie on general positions. In (III), all species are located along crystallographic threefold axes. PMID- 26870423 TI - Crystal structure of (E)-13-(pyrimidin-5-yl)parthenolide. AB - The title compound, C19H22N2O3, {systematic name (1aR,4E,7aS,8E,10aS,10bR)-1a,5 dimethyl-8-[(pyrimidin-5-yl)-methylid-ene]-2,3,6,7,7a,8,10a,10b-octa-hydro oxireno[2',3':9,10]cyclo-deca-[1,2-b]furan-9(1aH)-one} was obtained from the reaction of parthenolide [systematic name (1aR,7aS,10aS,10bR,E)-1a,5-dimethyl-8 methyl-ene-2,3,6,7,7a,8,10a,10b-octa-hydro-oxireno[2',3':9,10]cyclodeca-[1,2 b]furan-9(1aH)-one] with 5-bromo-pyrimidine under Heck reaction conditions, and was identified as an E isomer. The mol-ecule possesses ten-, five- (lactone) and three-membered (epoxide) rings with a pyrimidine group as a substituent. The ten membered ring displays an approximate chair-chair conformation, while the lactone ring shows a flattened envelope-type conformation. The dihedral angle between the pyrimidine moiety and the lactone ring system is 29.43 (7) degrees . PMID- 26870424 TI - Crystal structure of racemic cis-2-amino-1,2-di-phenyl-ethanol (ADE). AB - In the title racemic compound, C14H15NO, the hy-droxy and amino groups form a bent tweezer-like motif towards the phenyl groups. In the crystal, enanti-omers aggregate with each other and are linked by O-H?N hydrogen bonds, forming chiral 21-helical columnar structures from C(5) chains along the b-axis direction. Left- and right-handed 21 helices are formed from (1S,2R)-2-amino-1,2-di-phenyl-ethanol and (1R,2S)-2-amino-1,2-di-phenyl-ethanol, respectively. PMID- 26870425 TI - Crystal structure of 3-O-benzyl-4(R)-C-(1-benzyl-1H-1,2,3-triazol-4-yl)-1,2-O-iso propyl-idene-alpha-d-erythro-furan-ose. AB - The title compound, C23H25N3O4, {systematic name: 1-benzyl-4-[(3aR,5R,6R,6aR)-6 benz-yloxy-2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxol-5-yl]-1H-1,2,3 triazole}, consists of a substituted 2,2-di-methyl-tetra-hydro-furo[2,3 d][1,3]dioxole. The furan-ose ring adopts an envelope conformation close to C 3 exo, where the C atom substituted by the benz-yloxy group is the flap. The fused dioxolane ring also adopts an envelope conformation, with the methyl-ene C atom as the flap. In the crystal, mol-ecules are linked by weak C-H?O hydrogen bonds, forming zigzag chains along [010]. PMID- 26870426 TI - Crystal structure of 7-{[bis-(pyridin-2-ylmeth-yl)amino]-meth-yl}-5-chloro quinolin-8-ol. AB - In the title compound, C22H19ClN4O, the quinolinol moiety is almost planar [r.m.s. deviation = 0.012 A]. There is an intra-molecular O-H?N hydrogen bond involving the hy-droxy group and a pyridine N atom forming an S(9) ring motif. The dihedral angles between the planes of the quinolinol moiety and the pyridine rings are 44.15 (9) and 36.85 (9) degrees . In the crystal, mol-ecules are linked via C-H?O hydrogen bonds forming inversion dimers with an R 4 (4)(10) ring motif. The dimers are linked by C-H?N hydrogen bonds, forming ribbons along [01-1]. The ribbons are linked by C-H?pi and pi-pi inter-actions [inter-centroid distance = 3.7109 (11) A], forming layers parallel to (01-1). PMID- 26870427 TI - Ca4As3 - a new binary calcium arsenide. AB - The crystal structure of the binary compound tetra-calcium triarsenide, Ca4As3, was investigated by single-crystal X-ray diffraction. Ca4As3 crystallizes in the Ba4P3 structure type and is thus a homologue of isotypic Sr4As3. The unit cell contains 32 Ca(2+) cations, 16 As(3-) isolated anions and four centrosymmetric [As2](4-) dumbbells. The As atoms in each of the dumbbells are connected by a single bond, thus this calcium arsenide is a Zintl phase. PMID- 26870428 TI - Crystal structure of bis-(acetonyltri-phenyl-phospho-nium) tetra-chlorido cobaltate(II). AB - The complex title salt, (C21H20OP)2[CoCl4], is the reaction product of CoCl2 with acetonyltri-phenyl-phospho-nium chloride in aceto-nitrile. In the anion, the Co(II) atom exhibits a typical tetra-hedral environment, with Co-Cl distances ranging from 2.2721 (6) to 2.2901 (6) A, and with Cl-Co-Cl angles ranging from 106.12 (2) to 112.24 (2) degrees . The two phospho-nium cations likewise show the expected tetra-hedral configuration, with P-C distances ranging from 1.785 (2) to 1.8059 (18) A and C-P-C angles ranging from 106.98 (8) to 112.85 (15) degrees . The mol-ecules inter-act in the lattice mainly through Coulombic and van der Waals forces because there is no particular polarity to the charges carried by the cations or anion. In the crystal, the cations and anions are arranged in sheets parallel to (001). PMID- 26870429 TI - Crystal structure of bis-{MU-1-[(E)-(3-meth-oxy-phen-yl)diazen-yl]naphthalen-2 olato-kappa(3) N (2),O:O}bis-({1-[(E)-(3-meth-oxy-phen-yl)diazen-yl]naphthalen-2 olato-kappa(2) N (2),O}copper(II)). AB - The title dinuclear Cu(II) complex, [Cu2(C17H13N2O2)4], is located on an inversion centre. The Cu(II) atoms are each five-coordinated in a distorted square-pyramidal geometry by two N atoms and two O atoms from two bidentate ligands and one bridging O atom from another ligand. In the dinuclear complex, the Cu?Cu separation is 3.366 (3) A. In the crystal, complex mol-ecules are linked via weak C-H?O hydrogen bonds, forming a layer parallel to (-101). PMID- 26870430 TI - Crystal structure of 1,1'-bis-(2-meth-oxy-carbonyl-2-methyl-prop-yl)ferrocene. AB - The Fe atom in the title ferrocene derivative, [Fe(C11H15O2)2], is situated on an inversion centre. As a result of the point-group symmetry -1 of the mol-ecule, the ferrocene moiety adopts a staggered conformation. The average Fe-C(Cp) bond length (Cp is cyclo-penta-dien-yl) is 2.045 (4) A, in agreement with that of other disubstituted ferrocenes. The Fe-C bond length involving the substituted C atom is slightly longer [2.0521 (17) A] than the remaining Fe-C bond lengths caused by the inductive effect of the methyl-ene group on the Cp ring. Apart from van der Waals forces, no significant inter-molecular inter-actions are observed in the crystal packing. PMID- 26870431 TI - Crystal structure of di-aqua-[5,10,15,20-tetra-kis-(4-meth-oxy-phen yl)porphyrinato-kappa(4) N]iron(III) di-aqua-(18-crown-6)potassium bis-(tri fluoro-methane-sulfonate)-18-crown-6 (1/2). AB - In the title compound, [Fe(III)(C48H36N4O2)(H2O)2][K(C12H24O6)(H2O)2](SO3CF3)2.2C12H24O6, the Fe(III) atom is situated on an inversion centre and is octa-hedrally coordin-ated by four pyrrole N atoms of the deprotenated 5,10,15,20-tetra-kis-(4-meth-oxy-phen yl)porphyrinate ligand and two water mol-ecules. The average equatorial Fe N(pyrrole) bond length [2.043 (6) A] is consistent with a high-spin (S = 5/2) iron(III) metalloporphyrin derivative. The K(+) cation, which also lies on an inversion centre, is chelated by the six O atoms of one 18-crown-6 mol-ecule and is additionally coordinated by two water mol-ecules in a distorted hexa-gonal bipyramidal geometry. In the crystal, the cations, anions and one non coordinating 18-crown-6 mol-ecule are linked by classical O-H?O hydrogen bonds and non-conventional C-H?O hydrogen bonds, leading to a one-dimensional supra molecular architecture along [10-1]. The crystal packing is further stabilized by weak C-H?pi inter-actions involving pyrrole and phenyl rings of the porphyrins, as well as weak C-H?F contacts involving the (SO3CF3)(-) counter-ion and the 18 crown-6 mol-ecules. PMID- 26870432 TI - Crystal structure of di-MU-acetato-di-acetatobis-(MU-6,6'-dimeth-oxy-2,2' {[(propane-1,3-diylbis(aza-nylyl-idene)]bis-(methanylyl-idene)}diphenolato)tetra zinc. AB - The tetra-nuclear title complex, [Zn4(C19H20N2O4)2(CH3COO)4], is formed from two dinuclear motifs related by an inversion centre. The two crystallographically independent Zn(II) ions in the asymmetric unit are in different coordination environments. One is square-based pyramidal with one O atom of an acetate group occupying the axial position and two N and O atoms of one bmspd [H2bmspd = N,N' bis-(3-meth-oxy-salicyl-idene)propyl-ene-1,3-di-amine] Schiff base ligand forming the basal plane. The other Zn(II) atom is six-coordinated by four O atoms of the bmspd ligand forming the equatoral plane and two O atoms of different acetate groups located in the axial positions. As a result, the two phenolic planes of the bicompartmental Schiff base ligand are distorted slightly. However, the planes of the two Schiff base ligands are parallel. In addition, the Zn-N and Zn O bond lengths span the reasonable ranges 2.062 (2)-2.073 (2) and 1.9261 (15) 2.4356 (16) A, respectively. The Zn?Zn distances separated by phenolic O atoms are 3.2466 (4) A while the Zn?Zn distances bridged by acetate groups are 5.9835 (6) A. The tetra-nuclear moieties are connected by van der Waals interactions, and form a chain along c axis. PMID- 26870433 TI - Crystal structure of bis-{MU2-[(2-imino-cyclo-pentyl-idene)methyl-idene]aza-nido kappa(2) N:N'}bis-[(eta(5)-penta-methyl-cyclo-penta-dien-yl)zirconium(IV)] hexane monosolvate. AB - The title compound, [Zr2(C10H15)4(C6H6N2)2].C6H14, was obtained by the stoichiometric reaction of adipo-nitrile with [Zr(C10H15)2(eta(2)-Me3SiC2SiMe3)]. Intra-molecular nitrile-nitrile couplings and deprotonation of the substrate produced the (1-imino-2-enimino)-cyclo-pentane ligand, which functions as a five membered bridge between the two metal atoms. The Zr(IV) atom exhibits a distorted tetra-hedral coordination sphere defined by two penta-methyl-cyclo-penta-dienyl ligands, by the imino unit of one (1-imino-2-enimino)-cyclo-pentane and by the enimino unit of the second (1-imino-2-enimino)-cyclo-pentane. The cyclo-pentane ring of the ligand shows an envelope conformation. The asymmetric unit contains one half of the complex and one half of the hexane solvent mol-ecule, both being completed by the application of inversion symmetry. One of the penta-methyl-cyclo penta-dienyl ligands is disordered over two sets of sites with a refined occupancy ratio of 0.8111 (3):0.189 (3). In the crystal, the complex mol-ecules are packed into rods extending along [100], with the solvent mol-ecules located in between. The rods are arranged in a distorted hexa-gonal packing. PMID- 26870434 TI - Crystal structure of bis-(4-acetyl-anilinium) tetra-chlorido-cobaltate(II). AB - The structure of the title salt, (C8H10NO)2[CoCl4], is isotypic with the analogous cuprate(II) structure. The asymmetric unit contains one 4-acetyl anilinium cation and one half of a tetra-chlorido-cobaltate(II) anion for which the Co(II) atom and two Cl(-) ligands lie on a mirror plane. The Co-Cl distances in the distorted tetra-hedral anion range from 2.2519 (6) to 2.2954 (9) A and the Cl-Co-Cl angles range from 106.53 (2) to 110.81 (4) degrees . In the crystal, cations are self-assembled by inter-molecular N-H?O hydrogen-bonding inter actions, leading to a C(8) chain motif with the chains running parallel to the b axis. pi-pi stacking inter-actions between benzene rings, with a centroid-to centroid distance of 3.709 A, are also observed along this direction. The CoCl4 (2-) anions are sandwiched between the cationic chains and inter-act with each other through inter-molecular N-H?Cl hydrogen-bonding inter-actions, forming a three-dimensional network structure. PMID- 26870435 TI - Crystal structure of tri-aqua-(2,6-di-methyl-pyrazine-kappaN (4))bis-(thio cyanato-kappaN)manganese(II) 2,5-di-methyl-pyrazine disolvate. AB - In the crystal structure of the title complex, [Mn(NCS)2(C6H8N2)(H2O)3].2C6H8N2, the Mn(II) cation is coordinated by two terminally N-bonded thio-cyanate anions, three water mol-ecules and one 2,6-di-methyl-pyrazine ligand within a slightly distorted N3O3 octa-hedral geometry; the entire complex mol-ecule is generated by the application of a twofold rotation axis. The asymmetric unit also contains an uncoordinating 2,5-di-methyl-pyrazine ligand in a general position. Obviously, the coordination to the 2,6-di-methyl-pyrazine ligand is preferred because coordination to the 2,5-di-methyl-pyrazine is hindered due to the bulky methyl group proximate to the N atom. The discrete complexes are linked by water-O H?N(2,6-di-methyl-pyzazine/2,5-di-methyl-pyza-zine) hydrogen bonding, forming a three-dimensional network. In the crystal, mol-ecules are arranged in a way that cavities are formed in which unspecified, disordered solvent molecules reside. These were modelled employing the SQUEEZE routine in PLATON [Spek (2015 ?). Acta Cryst. C71, 9-18]. The composition of the unit cell does not take into account the presence of the unspecified solvent. PMID- 26870436 TI - Crystal structure of tris-(N-methyl-salicylaldiminato-kappa(2) N,O)vanadium(III). AB - The structure of the title complex, [V(C8H8NO)3], comprises neutral and discrete complexes, in which the V(III) cation is coordinated by three anionic N-methyl alicylaldiminate ligands within a slightly distorted mer-N3O3 octa-hedral geometry. In the crystal structure, the mol-ecules are linked via C-H?O hydrogen bonds into supra-molecular chains that extend along the c axis. PMID- 26870437 TI - Crystal structure of bis(bis{(E)-[(6-{(E)-[(4-fluorobenzyl)imino]methyl}pyridin-2 yl)methylidene](4-fluorophenyl)amine}nickel(II)) tetra-bromide nona-hydrate. AB - In the title complex, [Ni(C21H17F2N3)2]2Br4.9H2O, there are two independent metal complexes per asymmetric unit and two ligands per metal complex. The structural features (bond lengths and angles) of the two complexes are almost identical. In each complex, the nickel(II) ion is coordinated in an octa-hedral environment by six N atoms from two chelating (9E)-N-({6-[(E)-(4-fluoro-benzyl-imino)-meth yl]pyridin-2-yl}methyl-ene)(4-fluoro-phen-yl)methanammine ligands. The Ni-N bond lengths range from 1.973 (2) to 2.169 (2) A, while the chelate N-Ni-N angles range from 77.01 (10) to 105.89 (9) degrees . Additionally, there are four bromide anions and nine solvent water mol-ecules within the asymmetric unit. The water mol-ecules form a hydrogen-bonded network, displaying C-H?O, C-H?Br, O H?Br, O-H?O and O-H?F inter-actions into layers parallel to (111). In each unit, the fluoro-phenyl rings of one ligand are stacked with the central ring of the other ligand via pi-pi inter-actions, with the closest centroid-to-plane distances being 3.445 (5), 3.636 (5), 3.397 (5) and 3.396 (5) A. PMID- 26870438 TI - Crystal structure of a third polymorph of tris-(acetyl-acetonato-kappa(2) O,O')iron(III). AB - In the structure of the title complex, [Fe(C5H7O2)3] or Fe(acac)3, the asymmetric unit contains one mol-ecule in a general position. The coordination sphere of the Fe(III) atom is that of a slightly distorted octahedron. The crystal under investigation was a two-component pseudo-merohedral twin in the monoclinic system with a beta angle close to 90 degrees . Twin law [100/0-10/00-1] reduced the R1 residual [I > 2sigma(I)] from 0.0769 to 0.0312, and the mass ratio of twin components refined to 0.8913 (5):0.1087 (5). In the crystal, mol-ecules are arranged in sheets normal to [001] via non-classical C-H?O hydrogen bonding. No other significant inter-molecular inter-actions are observed. The structure is a new polymorph of Fe(acac)3 and is isotypic with one polymorph of its gallium analog. PMID- 26870439 TI - Crystal structure of [1-(3-eth-oxy-2-oxido-benzyl-idene-kappaO (2))-4-phenyl-thio semicarbazidato-kappa(2) N (1),S](tri-phenylphosphane-kappaP)nickel(II). AB - In the title complex, [Ni(C16H15N3O2S)(C18H15P)], the Ni(II) atom has a distorted tetra-hedral coordination geometry, comprised of N, S, O and P atoms of the tridentate thiosemicarbazide ligand and the P atom of the triphenylphosphane ligand. The benzene ring makes a dihedral angle of 53.08 (11) degrees with the phenyl ring of the phenyl-thio-semicarbazide moiety and dihedral angles of 73.69 (11), 20.38 (11) and 71.30 (11) degrees with the phenyl rings of tri-phenyl phosphane ligand. A pair of N-H?N hydrogen bonds generates an R 2 (2)(8) ring graph-set motif. The eth-oxy group is disordered over two positions, with site occupancies of 0.631 (9) and 0.369 (9). The mol-ecular structure is stabilized by a weak intra-molecular C-H?O hydrogen bond. In the crystal, weak N-H?N and C-H?pi inter-actions connect the mol-ecules, forming a three-dimensional network. PMID- 26870440 TI - Crystal structure of trans-di-aqua-bis-(1H-pyrazole-3-carboxyl-ato-kappa(2) N,O)copper(II) dihydrate. AB - In the title compound, [Cu(C4H3N2O2)2(H2O)2].2H2O, the Cu(II) ion is located on an inversion centre and exhibits an axially elongated octa-hedral coordination geometry. The equatorial plane is formed by two N,O-bidentate 1H-pyrazole-3 carboxyl-ate ligands in a trans configuration. The axial positions are occupied by two water mol-ecules. The mononuclear complex mol-ecules are arranged in layers parallel to the ab plane. Each complex mol-ecule is linked to four adjacent species through inter-molecular O-H?O and N-H?O hydrogen bonds that are established between the coordinating water mol-ecules and carboxyl-ate O atoms or protonated N atoms of the organic ligands. These layers are further connected into a three-dimensional network by additional hydrogen bonds involving solvent water mol-ecules and non-coordinating carboxyl-ate O atoms. PMID- 26870441 TI - Crystal structure of cis-bis-{4-phenyl-1-[(3R)-1,7,7-tri-methyl-2-oxobi-cyclo [2.2.1]heptan-3-ylidene]thio-semicarbazidato-kappa(3) O,N (1),S}cadmium(II) with an unknown solvent mol-ecule. AB - The reaction between the racemic mixture of the camphor-4-phenyl-thio semicarbazone derivative and cadmium acetate dihydrate yielded the title compound, [Cd(C17H20N3OS)2]. The Cd(II) ion is six-coordinated in a distorted octa-hedral environment by two deprotonated thio-semicarbazone ligands acting as an O,N,S-donor in a tridentate chelating mode, forming five-membered chelate rings. In the crystal, the mol-ecules are connected via pairs of N-H?S and C-H?S inter-actions, building centrosymmetric dimers. One of the ligands is disordered in the campher unit over two sets of sites with site-occupancy factors of 0.7 and 0.3. The structure contains additional solvent mol-ecules, which are disordered and for which no reasonable split model was found. Therefore, the data were corrected for disordered solvent using the SQUEEZE routine [Spek (2015 ?). Acta Cryst. C71, 9-18] in PLATON. Since the disordered solvents were removed by data processing, and the number of solvent entities was a suggestion only, they were not considered in the chemical formula and subsequent chemical or crystal information. PMID- 26870442 TI - Crystal structure of bis-(4-acetyl-anilinium) tetra-chlorido-mercurate(II). AB - The structure of the title salt, (C8H10NO)2[HgCl4], is isotypic with that of the cuprate(II) and cobaltate(II) analogues. The asymmetric unit contains one 4 acetyl-anilinium cation and one half of a tetra-chlorido-mercurate(II) anion (point group symmetry m). The Hg-Cl distances are in the range 2.4308 (7)-2.5244 (11) A and the Cl-Hg-Cl angles in the range of 104.66 (2)-122.94 (4) degrees , indicating a considerable distortion of the tetra-hedral anion. In the crystal, cations are linked by an inter-molecular N-H?O hydrogen-bonding inter-action, leading to a C(8) chain motif with the chains extending parallel to the b axis. There is also a pi-pi stacking inter-action with a centroid-to-centroid distance of 3.735 (2) A between neighbouring benzene rings along this direction. The anions lie between the chains and inter-act with the cations through inter molecular N-H?Cl hydrogen bonds, leading to the formation of a three-dimensional network structure. PMID- 26870443 TI - The crystal structure of a new polymorph of hexa-aqua-nickel(II) bis-(6-oxo-1,6 di-hydro-pyridine-3-carboxyl-ate). AB - In a new polymorph of the title salt, [Ni(H2O)6](C6H4NO3)2, the metal atom of the cationic complex lies on a symmetry centre and is coordinated by six water mol ecules to provide a quite regular octa-hedral coordination environment. These cations inter-act with 6-oxo-1,6-di-hydro-pyridine-3-carboxyl-ate anions through electrostatic inter-actions and by means of O-H?O and N-H?O hydrogen bonds involving the carboxyl-ate, keto and protonated imine groups of the anion, and the coordinating water mol-ecules from the cationic complex entity to generate a supra-molecular three-dimensional architecture. The previously reported polymorph of this compound presents a network of hydrogen bonds, in which the organic anions establish mutual hydrogen-bonding inter-actions involving their keto and protonated imine groups. PMID- 26870444 TI - Crystal structure of bis-(1,3-di-amino-propane-kappa(2) N,N')bis-[2-(4-nitro-phen yl)acetato-kappaO]zinc(II). AB - In the structure of the title compound, [Zn(C8H6NO4)2(C3H10N2)2], the Zn(II) atom is located on a center of symmetry with one independent Zn-O distance of 2.199 (2) A, and two Zn-N distances of 2.157 (2) and 2.144 (2) A. The overall coordination geometry around the Zn(II) atom is octa-hedral. Several types of hydrogen-bonding inter-actions are evident. Both intra-molecular [2.959 (3) A] and inter-molecular [3.118 (3) and 3.124 (3) A inter-actions occur between the O atoms of the acetate group and the amino N atoms, and weak inter-molecular C-H-O inter-actions involving the nitro groups, leading to an extended chain of the molecules aligned along the ac plane. PMID- 26870445 TI - Crystal structure of di-aqua-bis-(2,6-di-methyl-pyrazine-kappaN (4))bis-(thio cyanato-kappaN)cobalt(II) 2,5-di-methyl-pyrazine monosolvate. AB - In the crystal structure of the title compound, [Co(NCS)2(C6H8N2)2(H2O)2].C6H8N2, the Co(II) cation is coordinated by the N atoms of two terminal thio-cyanate anions, the O atoms of two water mol-ecules and two N atoms of two 2,6-di-methyl pyrazine ligands. The coordination sphere of the resulting discrete complex is that of a slightly distorted octa-hedron. The asymmetric unit comprises a Co(II) cation and half of a 2,5-di-methyl-pyrazine ligand, both of which are located on centres of inversion, and a water ligand, a 2,6-di--methyl-pyrazine ligand and one thio-cyanate anion in general positions. In the crystal, the discrete complexes are arranged in such a way that cavities are formed in which the 2,5-di methyl-pyrazine solvent mol-ecules are located. The coordination of the 2,5-di methyl-pyrazine mol-ecules to the metal is apparently hindered due to the bulky methyl groups in vicinal positions to the N atoms, leading to a preferential coordination of the 2,6-di-methyl-pyrazine ligands. The discrete complexes are linked by O-H?N hydrogen bonds between one water H atom and the non-coordinating N atom of the 2,6-di-methyl-pyrazine ligands. The remaining water H atom is hydrogen bonded to one N atom of the 2,5-di-methyl-pyrazine solvent mol-ecule. This arrangement leads to the formation of a two-dimensional network extending parallel to (010). PMID- 26870446 TI - Redetermination of the crystal structure of 3,5-di-methyl-pyrazolium beta-octa molybdate tetra-hydrate. AB - The title compound, (C5H9N2)4[Mo8O26].4H2O, was reported previously from a room temperature data collection from which only the metal atoms could be refined anisotropically [FitzRoy et al. (1989 ?). Inorg. Chim. Acta, 157, 187-194]. The current redetermination at 180 (2) K models all the non-H atoms with anisotropic displacement parameters and fully describes the supra-molecular N-H?O and O-H?O hydrogen-bonded network connecting the 3,5-di-methyl-pyrazolium cations, the water mol-ecules of crystallization and the beta-octa-molybdate anion. All H atoms involved in the three-dimensional hydrogen-bonding network could be located from difference Fourier maps, with the exception of those of one disordered water mol-ecule, firstly seen in this structural report [refined over two distinct locations with site-occupancy factors of 0.65 (2) and 0.35 (2)]. The complete beta-octa-molybdate anion is generated by a crystallographic inversion centre. PMID- 26870447 TI - Crystal structure of bis-{N-[(di-ethyl-amino)-dimethyl-sil-yl]anilido-kappa(2) N,N'}zinc. AB - The title zinc amide, [Zn(C12H21N2Si)2], was prepared by the metathetical reaction of [LiN(SiMe2NEt2)(C6H5)]2 with zinc dichloride. It is mononuclear and the mol-ecule is generated by twofold rotation symmetry. The central Zn(II) atom is N,N'-chelated by each of the two N-silylated anilide ligands in a highly distorted tetra-hedral environment. Two N-Si-N ligands are arranged in a cis fashion around the Zn(II) atom. The Zn-Namine bonds [2.2315 (12) A] are much longer than the Zn-Nanilide bonds [1.9367 (11) A]. PMID- 26870448 TI - Crystal structure of tris-(N-methyl-salicyl-aldiminato-kappa(2) N,O)chromium(III). AB - The crystal structure of the title compound, [Cr(C8H8NO)3], is isotypic with the vanadium(III) analogue. The asymmetric unit consists of one Cr(3+) cation and three N-methyl-salicylaldiminate anions. The metal cation is octa-hedrally coordinated by three N,O-chelating N-methyl-salicylaldiminate ligands, leading to discrete and neutral complexes. In the crystal, neighbouring complexes are linked via C-H?O hydrogen-bonding inter-actions into chains propagating parallel to the c axis. PMID- 26870449 TI - Crystal structure of bis-[MU-S-hexyl 3-(2-oxido-benzyl-idene)di-thio-carbazato kappa(4) O,N (3),S:O]dicopper(II). AB - The title compound, [Cu2(C14H18N2OS2)2], is a binuclear copper(II) complex of an oxybenzyl-idenedi-thio-carbazate ligand. The ligand coordinates in a tridentate manner through N-, S- and O-donor atoms. Each O atom also bridges to a second Cu(II) ion to form the binuclear species. It has a central Cu2O2 rhomboid moiety and a metal-to-metal separation of 2.9923 (6) A. In the crystal, the binuclear complexes stack along the a axis with all the hexyl chains located side-by-side, forming a hydro-phobic region. The complexes are linked via C-H?N hydrogen bonds, forming chains along the c-axis direction. One Cu(II) atom has the S atom of a symmetry-related complex located approximately in the apical position at 2.9740 (11) A. This weak inter-action links the chains to form slabs parallel to the ac plane. PMID- 26870450 TI - Crystal structure of bis-(1,3-di-meth-oxy-imidazolin-2-yl-idene)silver(I) hexa fluorido-phosphate, N-heterocyclic carbene (NHC) complex. AB - The title salt, [Ag(C5H8N2O2)2]PF6, was obtained by deprotonation and metalation of 1,3-di-meth-oxy-imidazolium hexa-fluorido-phosphate using silver(I) oxide in methanol. The C-Ag-C angle in the cation is 178.1 (2) degrees , and the N-C-N angles are 101.1 (4) and 100.5 (4) degrees . The meth-oxy groups adopt an anti conformation. In the crystal, anions (A) are sandwiched between cations (C) in a layered arrangement {C...A...C} n stacked along [001]. Within a C...A...C layer, the hexafluoridophosphate anions accept several C-H?F hydrogen bonds from the cationic complex. PMID- 26870451 TI - Crystal structure of {bis-[(1H-benzimid-azol-2-yl-kappaN (3))meth yl]sulfane}dichloridomercury(II). AB - In the asymmetric unit of the title compound, [HgCl2(C16H14N4S)], the Hg(II) cation is linked to two Cl atoms and two imidazole N atoms of the chelating bis [(1H-benzimidazol-2-yl)meth-yl]sulfane ligand, forming a slightly distorted tetra hedral environment. The substitued imidazole rings of the ligand are almost perfectly planar [with maximum deviations of 0.017 (3) and 0.012 (3) A] and form a dihedral angle of 42.51 (5) degrees . The crystal packing can be described as alternating layers parallel to (010). In this arrangement, N-H?Cl hydrogen bonds between the N-H groups of the benzimidazole moieties and chloride ligands are responsible for the formation of the chain-like packing pattern along [010] exhibiting a C(6) graph-set motif. PMID- 26870452 TI - Crystal structure of catena-poly[1,3-di-benzyl-benzimidazolium [[chlorido mercurate(II)]-di-MU-chlorido]]. AB - The asymmetric unit of the polymeric title compound, {(C21H19N2)[HgCl3]} n , comprises one-half of the cationic mol-ecule, the other half being generated by application of twofold rotation symmetry, one Hg and two Cl atoms. The Hg(II) atom, lying on a twofold rotation axis, exhibits a distorted triangular coordination environment and is surrounded by three Cl atoms with Hg-Cl distances in the range 2.359 (2)-2.4754 (13) A. Two additional longer distances [Hg?Cl = 3.104 (14) A] lead to the formation of polymeric [HgCl1/1Cl4/2](-) chains extending along [001]. The crystal packing can be described by cationic layers alternating parallel to (-110) with the anionic chains located between the layers. The packing is consolidated by pi-pi stacking inter-actions between the benzene rings of the central benzimidazole entities, with centroid-to-centroid distances of 3.643 (3) A. PMID- 26870453 TI - Crystal structure of dimethyl-1kappa(2) C-bis(MU-4-methylphenolato-1:2kappa(2) O:O)(N,N,N',N'-tetramethylethylenediamine-2kappa(2) N,N')indium(III)lithium(I). AB - The mixed bimetallic title compound, [InLi(CH3)2(C7H7O)2(C6H16N2)] or [(tmeda)Li MU-(4-MeC6H4O)2InMe2] (tmeda is N,N,N',N'-tetra-methyl-ethylenedi-amine), exhibits a four-membered LiO2In ring core via bridging 4-methyl-phenolate groups. The Li and In atoms are in distorted tetra-hedral N2O2 and C2O2 bonding environments, respectively. The Li atom is further chelated by a tmeda group, yielding a spiro-cyclic structure. PMID- 26870454 TI - Crystal structure of di-MU2-chlorido-bis-[(1-aza-4-azoniabi-cyclo-[2.2.2]octane kappaN (1))di-chlorido-dicadmium]. AB - In the structure of the binuclear title compound, [Cd2(C6H13N2)2Cl6], two Cd(II) atoms are bridged by two Cl(-) ligands, defining a centrosymmetric Cd2Cl2 motif. Each metal cation is additionally coordinated by two Cl(-) ligands and the N atom of a protonated 1,4-di-aza-bicyclo-[2.2.2]octane (H-DABCO)(+) ligand, leading to an overall trigonal-bipyramidal coordination environment with one of the bridging Cl(-) ligands and the N atom at the apical sites. In the crystal, the neutral dimers are linked via N-H?Cl hydrogen bonds, forming a two-dimensional network expanding parallel to (100). PMID- 26870455 TI - Crystal structure of 8-iodo-quinolinium tetra-chlorido-aurate(III). AB - The structure of the title salt, (C9H7IN)[AuCl4], is comprised of planar 8-iodo quinolinium cations (r.m.s. deviation = 0.05 A) and square-planar tetra-chlorido aurate(III) anions. The asymmetric unit contains one 8-iodo-quinolinium cation and two halfs of [AuCl4](-) anions, in each case with the central Au(III) atom located on an inversion center. Inter-molecular halogen-halogen contacts were found between centrosymmetric pairs of I [3.6178 (4) A] and Cl atoms [3.1484 (11), 3.3762 (13), and 3.4935 (12) A]. Inter-molecular N-H?Cl and C-H?Cl hydrogen bonding is also found in the structure. These inter-actions lead to the formation of a three-dimensional network. Additionally, there is an intra-molecular N-H?I hydrogen bond between the aromatic iminium and iodine. There are no aurophilic inter-actions or short contacts between I and Au atoms, and there are no notable pi-stacking inter-actions between the aromatic cations. PMID- 26870456 TI - Crystal structure of di-bromido-tetra-kis(propan-2-ol-kappaO)nickel(II). AB - The asymmetric unit of the mononuclear title complex, [NiBr2(C3H8O)4], comprises a Ni(II) cation located on a centre of inversion, one Br(-) anion and two propan 2-ol ligands. The Ni(II) cation exhibits a distorted trans-Br2O4 environment. There are O-H?Br hydrogen bonds connecting neighbouring mol-ecules into rows along [100]. These rows are arranged in a distorted hexa-gonal packing and are held together by van der Waals forces only. PMID- 26870457 TI - Crystal structure of bis-(MU-2-benzoyl-benzoato-kappa(2) O:O')bis-[bis-(2,2'-bi pyridine-kappa(2) N,N')manganese(II)] bis-(perchlorate). AB - The title compound, [Mn2(C6H5COC6H4COO)2(C10H8N2)4](ClO4)2, comprises a centrosymmetric binuclear cation and two perchlorate anions. In the complex cation, two Mn(II) atoms are bridged by two O atoms of two different 2-benzoyl benzoate ligands, each Mn(II) atom being further coordinated by two 2,2'-bi pyridine (bipy) ligands in a distorted octa-hedral environment. Within the binuclear mol-ecule, the Mn?Mn separation is 4.513 (7) A. Inter-molecular C-H?O and C-H? pi inter-actions link the mol-ecules into a three-dimensional network. PMID- 26870458 TI - Crystal structure of a one-dimensional coordination polymer of tin(IV) bromide with 1,4-di-thiane. AB - The title compound, [SnBr4(C4H8S2)] {systematic name: catena poly[[tetrabromidotin(IV)]-MU-1,4-dithiane-kappa(2) S:S']}, represents the first 1,4-di-thiane complex with tin as coordination centre. The asymmetric unit consist of half a formula unit with the tin(IV) atom at the centre of symmetry at 0,0,1/2 (Wyckoff symbol b) and a centrosymmetric 1,4-di-thiane mol-ecule with the centre of symmetry in 1/2,0,1 (Wyckoff symbol c). The tin(IV) atom is coordinated in a distorted octa-hedral manner by the four bromine atoms and two sulfur atoms of two 1,4-di-thiane mol-ecules in a trans-position. Sn-Br [mean value: 2.561 (5) A] and Sn-S distances [2.6546 (6) A] are in the typical range for octa-hedrally coordinated tin(IV) atoms and the di-thiane mol-ecule adopts a chair conformation. The one-dimensional polymeric chains propagate along the [101] direction with weak inter-molecular Br?Br [3.5724 (4) A] between parallel chains and weak Br?H inter-actions [2.944-2.993 A] within the chains. PMID- 26870459 TI - Crystal structure of di-aqua-bis-(2,6-di-methyl-pyrazine-kappaN)bis-(thio-cyanato kappaN)cobalt(II) 2,5-di-methyl-pyrazine tris-olvate. AB - In the crystal structure of the title compound, [Co(NCS)2(C6H8N2)2(H2O)2].3C6H8N2, the Co(II) cation is coordinated by two terminally N-bound thio-cyanate anions, two water mol-ecules and two 2,6-di methyl-pyrazine ligands, forming a discrete complex with a slightly distorted octa-hedral N4O2 coordination environment. The asymmetric unit contains one Co(II) cation and three halves of 2,5-di-methyl-pyrazine solvate mol-ecules, all entities being completed by inversion symmetry, as well as one thio-cyanate anion, an aqua ligand and a 2,6-di-methyl-pyrazine ligand, all in general positions. In the crystal, discrete complexes are arranged in a way that cavities are formed where the noncoordinating 2,5-di-methyl-pyrazine mol-ecules are located. The coordination of the latter to the metal is prevented due to the bulky methyl groups in vicinal positions to the N atoms, leading to a preferential coordination through the 2,6-di-methyl-pyrazine ligands. The complex mol-ecules are linked by O-H?N hydrogen bonds between the water H atoms and the N atoms of 2,5-di-methyl-pyrazine solvent mol-ecules, leading to a layered structure extending parallel to (100). PMID- 26870460 TI - Crystal structure of tris-(MU-bis-{4-[(pyridin-2-yl-methyl-idene)amino]-phen yl}methane-kappa(4) N,N':N'',N''')dizinc tetra-kis-(tetra-fluorido-borate) aceto nitrile tris-olvate. AB - The asymmetric unit of the title compound, [Zn2(C25H20N4)3](BF4)4.3CH3CN, consists of one dinuclear Zn(II) complex cation with a triple-helical [Zn2 L 3](4+) motif (L is bis-{4-[(pyridin-2-yl-methyl-idene)amino]-phen-yl}methane), four BF4 (-) anions and three CH3CN solvent mol-ecules. The Zn?Zn separation is 11.3893 (14) A and the ligands wrap around the two Zn(II) atoms, forming a triple helix as defined by the Zn-N-N-Zn torsion angles of 104.05 (18), 99.06 (19) and 101.40 (19) degrees . The Zn-N(pyrid-yl) distances in the octahedral ZnN6 coordination sphere are in the range 2.128 (5)-2.190 (5) A and the Zn-N(imine) distances are in the range 2.157 (5)-2.277 (5) A. PMID- 26870461 TI - Crystal structure of bis-(quinolin-1-ium) tetra-chlorido-ferrate(III) chloride. AB - The asymmetric unit of the title hybrid compound, (C9H8N)[FeCl4]Cl, comprises a tetra-hedral tetra-chlorido-ferrate(III) anion, [FeCl4](-), a Cl(-) anion and two quinolinium cations. There are N-H?Cl hydrogen-bonding inter-actions between the protonated N atoms of the quinolinium cations and the chloride anion, which together with pi-pi stacking between adjacent quinolinium rings [centroid-to centroid distances between C6 and C5N rings in adjacent stacked quinolinium cations of 3.609 (2) and 3.802 (2) A] serve to hold the structure together. PMID- 26870462 TI - Crystal structure of tri-hydrogen bis-{[1,1,1-tris-(2-oxido-ethyl-amino-meth yl)ethane]-cobalt(III)} trinitrate. AB - The title compound, [Co2(L)2](3+).3NO3 (-) [where L = CH3C(CH2NHCH2CH2OH1/2)3], has been synthesized from the ligand 1,1,1-tris-(2-hy-droxy-ethyl-amino-meth yl)ethane. The cobalt(III) dimer has an inter-esting and uncommon O-H?O hydrogen bonding motif with the three bridging hy-droxy H atoms each being equally disordered over two positions. In the dimeric trication, the octa-hedrally coordinated Co(III) atoms and the capping C atoms lie on a threefold rotation axis. The N atoms of two crystallographically independent nitrate anions also lie on threefold rotation axes. N-H?O hydrogen bonding between the complex cations and nitrate anions leads to the formation of a three-dimensional network structure. The compound is a racemic conglomerate of crystals containing either d or l mol-ecules. The crystal used for this study is a d crystal. PMID- 26870463 TI - Crystal structure of (E)-5-benz-yloxy-2-{[(4-nitro-phen-yl)imino]-meth-yl}phenol. AB - In the title compound, C20H16N2O4, the mol-ecule adopts an E conformation about the N=C bond. There is an intra-molecular O-H?N hydrogen bond forming an S(6) ring motif. The nitro-benzene and benz-yloxy rings are inclined to the central benzene ring by 4.34 (10) and 27.66 (11) degrees , respectively, and to one another by 31.40 (12) degrees . In the crystal, mol-ecules are linked via C-H?O hydrogen bonds, forming zigzag chains along [001]. Within the chains there are C H?pi inter-actions present. The chains are linked via pi-pi inter-actions [inter centroid distance = 3.7048 (15) A], forming slabs parallel to the bc plane. PMID- 26870464 TI - Crystal structure of (tert-butyl-carbamo-yl)(4-chloro-2-oxo-2H-chromen-3 yl)methyl acetate. AB - In the title compound, C17H18ClNO5, which was synthesized by reacting 4-chloro-3 formyl-coumarin, acetic acid and tert-butyl isocyanide, the acetamido side chain is convoluted with ring-to-side chain C-C-C-C, C-C-C-N and C-C-N-C torsion angles of -123.30 (14), -135.73 (12) and 176.10 (12) degrees , respectively. In the crystal, N-H?O and weak C-H?O hydrogen bonds are present, which together with pi pi coumarin-ring inter-actions [ring centroid separations = 3.4582 (8) and 3.6421 (9) A], give rise to a layered structure lying parallel to (001). PMID- 26870465 TI - Crystal structure of 3,4-dimethyl 2-(tert-butyl-amino)-5-[2-oxo-4-(thio-morpholin 4-yl)-2H-chromen-3-yl]furan-3,4-di-carboxyl-ate ethyl acetate hemisolvate. AB - In the title hemisolvate, C25H28N2O7S.0.5C4H8O2, the thio-morpholine ring adopts a chair conformation, with the exocyclic N-C bond in an equatorial orientation. The dihedral angle between the coumarin ring system (r.m.s. deviation = 0.044 A) and the furan ring is 64.84 (6) degrees . An intra-molecular N-H?O hydrogen bond closes an S(6) ring. The ethyl acetate solvent mol-ecule is disordered about a crystallographic inversion centre. In the crystal, the components are linked by C H?O and C-H?S hydrogen bonds, generating a three-dimensional network. PMID- 26870466 TI - Crystal structure of 2-oxo-N'-phenyl-2H-chromene-3-carbohydrazide. AB - In the title compound, C16H12N2O3, the 2H-chromene moiety is essentially planar, with an r.m.s. deviation of the nine constituent atoms from the mean plane of 0.0093 A, and makes a dihedral angle of 76.84 (3) degrees with the pendant phenyl ring. An intra-molecular N-H?O hydrogen bond helps to determine the conformation of the side chain. In the crystal, N-H?O and N-H?N hydrogen bonds link the mol-ecules, forming [100] chains. PMID- 26870467 TI - Crystal structure of cyproconazole. AB - The title compound [systematic name: 2-(4-chloro-phen-yl)-3-cyclo-propyl-1-(1H 1,2,4-triazol-1-yl)butan-2-ol], C15H18ClN3O, is a conazole fungicide. The asymmetric unit comprises two enanti-omeric pairs (mol-ecules A and B) in which the dihedral angles between the chloro-phenyl and triazole rings are 46.54 (9) (mol-ecule A) and 67.03 (8) degrees (mol-ecule B). In the crystal, C-H?O, O-H?N and C-H?Cl hydrogen bonds and weak C-H?pi inter-actions [3.473 (2) A] link adjacent mol-ecules, forming columns along the a axis. PMID- 26870468 TI - Crystal structure of a methimazole-based ionic liquid. AB - The structure of 1-methyl-2-(prop-2-en-1-ylsulfan-yl)-1H-imidazol-3-ium bromide, C7H11N2S(+).Br(-), has monoclinic (P21/c) symmetry. In the crystal, the components are linked by N-H?Br and C-H?Br hydrogen bonds. The crystal structure of the title compound undeniably proves that methimazole reacts through the thione tautomer, rather than the thiol tautomer in this system. PMID- 26870469 TI - Crystal structure of (Z)-3-allyl-5-(3-bromo-benzyl-idene)-2-sulfanyl-idene-1,3 thia-zolidin-4-one. AB - In the title compound, C13H10BrNOS2, the rhodanine (systematic name: 2-sulfanyl idene-1,3-thia-zolidin-4-one) and the 3-bromo-benzyl-idene ring systems are inclined slightly, forming a dihedral angle of 5.86 (12) degrees . The rhodanine moiety is linked to an allyl group at the N atom and to the 3-bromo-benzyl-idene ring system. The allyl group, C=C-C, is nearly perpendicular to the mean plane through the rhodanine ring, maling a dihedral angle of 87.2 (5) degrees . In the crystal, mol-ecules are linked by pairs of C-H?O hydrogen bonds, forming inversion dimers with an R 2 (2)(10) ring motif. PMID- 26870470 TI - Crystal structure of (Z)-3-allyl-5-(4-chloro-benzyl-idene)-2-sulfanyl-idene-1,3 thia-zolidin-4-one. AB - In the title compound, C13H10ClNOS2, the dihedral angle between the rhodanine (r.m.s. deviation = 0.008 A) and 4-chloro-benzyl-idene rings is 1.79 (11) degrees . The allyl group attached to the N atom, which lies almost perpendicular to the rhodanine ring, is disordered over two orientations in a 0.519 (13):0.481 (13) ratio. A short intra-molecular C-H?S inter-action closes an S(6) ring. In the crystal, mol-ecules are linked by pi-pi stacking inter-actions [centroid-centroid separation = 3.600 (15) A], generating inversion dimers. PMID- 26870471 TI - Crystal structure of (1R,3S,8R,11R)-11-acetyl-3,7,7-trimethyl-10-oxatri-cyclo [6.4.0.0(1,3)]dodecan-9-one. AB - The title compound, C16H24O3, is built up from three fused rings, a six-membered, a seven-membered and a three-membered ring. The absolute configuration of the title compound was determined as (1R,3S,8R,11R) based on the synthetic pathway. The six-membered ring has an half-chair conformation whereas the seven-membered ring displays a boat conformation. In the cyrstal, C-H?O hydrogen bonds build up a two-dimensional network parallel to (0 0 1). The crystal studied was an inversion twin with a minor twin component of 34%. PMID- 26870472 TI - Crystal structure of (tert-butyl-dimethyl-sil-yl)tri-phenyl-germane, Ph3Ge SiMe2(t-Bu). AB - In the title compound, Ph3Ge-SiMe2(t-Bu) or C24H30GeSi, the Si and Ge atoms both possess a tetra-hedral coordination environment with C-E-C (E = Si, Ge) angles in the range 104.47 (5)-114.67 (5) degrees . The mol-ecule adopts an eclipsed conformation, with three torsion angles less than 29.5 degrees . In the crystal, neighbouring mol-ecules are combined to dimers by six T-shaped C-H?pi inter actions, forming sixfold phenyl embraces (6PE). PMID- 26870473 TI - Crystal structure of 2-amino-4-(4-meth-oxy-phen-yl)-4H-benzo[g]chromene-3-carbo nitrile. AB - In the title compound, C21H16N2O2, the naphthalene fragment is twisted slightly, as indicated by the dihedral angle of 3.2 (2) degrees between the two six membered rings. The pendant 4-meth-oxy-phenyl ring makes a dihedral angle of 86.08 (6) degrees with the central six-membered ring of the 4H-benzo[g]chromene ring system. In the crystal, mol-ecules are linked by pairs of N-H?N hydrogen bonds, forming inversion dimers which are linked into chains propagating in the b axis direction by N-H?O hydrogen bonds. PMID- 26870474 TI - Crystal structure of 3,4-di-meth-oxy-phenol. AB - The title compound, C8H10O3, has two planar mol-ecules in the asymmetric unit possessing mean deviations from planarity of 0.051 and 0.071 A. In the crystal, there are two distinct infinite chains, both along [010]. The chains are formed by O-H?O inter-actions between the phenol and both the 3-meth-oxy and the 4-meth oxy groups. PMID- 26870475 TI - Crystal structure of 3-(4-methyl-phen-yl)-1-phenyl-5-[(E)-2-phenyl-ethen-yl]-1H pyrazole. AB - In the title compound, C24H20N2, the dihedral angles between the pyrazole ring and the pendant phenyl, toluoyl and phenyl-ethenyl rings are 41.50 (8), 4.41 (8) and 31.07 (8) degrees , respectively. In the crystal, inversion dimers linked by a pi-pi stacking inter-actions between the phenyl-ethenyl rings are observed [centroid-centroid separation = 3.5857 (9) A]. PMID- 26870476 TI - Crystal structure of 4-(4-meth-oxy-phen-oxy)benzaldehyde. AB - The title compound, C14H12O3, was synthesized via the nucleophilic addition of 4 meth-oxy-phenol to 4-fluoro-benzaldehyde. The dihedral angle between the least squares planes of the benzene rings is 71.52 (3) degrees and the C-O-C angle at the central O atom is 118.82 (8) degrees . In the crystal, weak C-H?O hydrogen bonds link the molecules to generate supra-molecular layers in the bc plane. The layers are linked by weak C-H?pi inter-actions. PMID- 26870477 TI - Crystal structure of (Z)-ethyl 2-{5-[(2-benzyl-idene-3-oxo-2,3-di-hydro benzo[b][1,4]thia-zin-4-yl)meth-yl]-1H-1,2,3-triazol-1-yl}acetate. AB - The title compound, C22H20N4O3S, features two fused six-membered rings linked to a 1,2,3-triazole ring which is attached to an ethyl acetate group. The heterocycle in the benzo-thia-zine residue has an envelope conformation with the S atom being the flap. The conformation of the ethyl acetate side chain, which is directed to the same side of the mol-ecule as the C6 ring of the fused-ring system, may be partially established by a pair of weak intra-molecular C H?O(carbon-yl) inter-actions. The three-dimensional packing is aided by inter molecular C-H?O and C-H?N inter-actions. PMID- 26870478 TI - Crystal structure of 5-bromo-1-ethyl-indoline-2,3-dione. AB - The title compound, C10H8BrNO2, crystallizes with two independent molcules (A and B) in the asymmetric unit. In each mol-ecule, the indoline ring system is almost planar, with the largest deviation from the mean plane being 0.016 (2) A in mol ecule A and 0.040 (13) A in mol-ecule B. In each mol-ecule, the ethyl group is nearly perpendicular to the indoline ring system with C-C-N-C torsion angles of 94.8 (3) and 93.0 (3) degrees in mol-ecules A and B, respectively. In the crystal, the two mol-ecules are inclined to each other, making a dihedral angle of 6.28 (8) degrees . In the molecular packing, the A and B mol-ecules are linked by C-H?O hydrogen bonds, forming -A-B-A-B- chains along [01-1]. Parallel chains are linked via a weak slipped parallel pi-pi inter-action [inter-centroid distance = 3.6107 (14) A] and a short Br?O contact [3.183 (2) A], forming a three dimensional structure. PMID- 26870479 TI - Crystal structure of N''-(2-eth-oxy-2-oxoeth-yl)-N,N,N',N'-tetra-methyl-N''-[3 (1,3,3-tri-methyl-ureido)prop-yl]guanidinium tetra-phenyl-borate. AB - In the title salt, C16H34N5O3 (+).C24H20B(-), the C-N bond lengths in the cation are 1.3368 (16), 1.3375 (18) and 1.3594 (17) A, indicating partial double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal-planar geometry and the positive charge is delocal-ized in the CN3 plane. In the crystal, weak C-H?O contacts are observed between neighbouring guanidinium ions and between guanidinium ions and tetra-phenyl-borate anions. In addition, C-H?pi inter-actions involving guanidinium H atoms and aromatic rings of the anion are present. The phenyl rings form aromatic pockets, in which the cations are embedded. This leads to the formation of a two-dimensional supramolecular pattern along the ab plane. PMID- 26870480 TI - Crystal structure of ethyl 3-(4-chloro-phen-yl)-5-[(E)-2-(di-methyl-amino)-ethen yl]-1,2-oxazole-4-carboxyl-ate. AB - In the title compound, C16H17ClN2O3, two mol-ecules, A and B, with different conformations, comprise the asymmetric unit. In mol-ecule A, the C=O group of the ester points away from the benzene ring [C-C-C=O = -170.8 (3) degrees ], whereas in mol-ecule B, it points back towards the benzene ring [C-C-C=O = 17.9 (4) degrees ]. The dihedral angles betweeen the oxazole and benzene rings also differ somewhat [46.26 (13) for mol-ecule A and 41.59 (13) for mol-ecule B]. Each mol ecule features an intra-molecular C-H?O inter-action, which closes an S(6) ring. In the crystal, the B mol-ecules are linked into [001] C(12) chains by weak C H?Cl inter-actions. PMID- 26870481 TI - Crystal structure of (E)-diethyl 2-[(1-phenyl-sulfonyl-1H-indol-3-yl)methyl idene]succinate. AB - In the title compound, C23H23NO6S, the phenyl ring is perpendicular [dihedral angle = 89.34 (9) degrees ] to the indole ring system. In the mol-ecule, the eth oxy groups are each disordered over two sets of sites with occupancy ratios of 0.671 (6):0.329 (6) and 0.75 (3):0.25 (3). The mol-ecular conformation is consolidated by a weak C-H?O interaction, which generates an S(6) graph-set motif. The packing of the mol-ecules in the crystal structure features weak C H?pi inter-actions. PMID- 26870482 TI - Crystal structure of 5-[4-(di-methyl-amino)-phen-yl]-3-(4-methyl-phen-yl)-4,5-di hydro-1H-pyrazole-1-carbaldehyde. AB - The title compound, C19H21N3O, comprises a central pyrazole ring which is N connected to an aldehyde group and C-connected twice to substituted benzene rings. The pyrazole ring is twisted on the C-C single bond, and the least-squares plane through this ring forms dihedral angles of 82.44 (5) and 4.52 (5) degrees with the (di-methyl-amino)-benzene and p-tolyl rings, respectively. In the crystal, weak C-H?O hydrogen bonds link mol-ecules into supra-molecular tubes along the b axis. PMID- 26870483 TI - Crystal structure of pyrazoxyfen. AB - The title compound, C20H16Cl2N2O3 (systematic name: 2-{[4-(2,4-di-chloro-benzo yl)-1,3-di-methyl-pyrazol-5-yl}-oxy}-1-phenyl-ethan-1-one), is the benzoyl pyrazole herbicide pyrazoxyfen. The asymmetric unit comprises two independent mol ecules, A and B, in which the pyrazole ring makes dihedral angles of 80.29 (10) and 61.70 (10) degrees and 87.60 (10) and 63.92 (8) degrees , respectively, with the di-chloro-phenyl and phenyl rings. In the crystal, C-H?O and C-H?N hydrogen bonds, and C-H?pi and pi-pi [3.646 (2) A] inter-actions link adjacent mol-ecules, forming a two-dimensional network parellel to (011). In addition, the networks are linked by weak inter-molecular C-Cl?pi [3.356 (2), 3.950 (2), 3.250 (2) and 3.575 (2) A] inter-actions, resulting in a three-dimensional architecture. PMID- 26870484 TI - Crystal structure of benzobi-cyclon. AB - In the title compound, C22H19ClO4S2 [systematic name: 3-(2-chloro-4-mesylbenzo yl)-4-(phenyl-sulfan-yl)bi-cyclo-[3.2.1]oct-3-en-2-one], which is an unclassified herbicide, the dihedral angle between the plane of the phenyl and chloro-benzene rings is 19.9 (2) degrees . In the crystal, C-H?O hydrogen bonds link adjacent mol-ecules, generating two-dimensional networks extending parellel to (011). PMID- 26870485 TI - Crystal structure of 13-phenyl-2,3,4,13-tetra-hydro-1H-indazolo[1,2-b]phthalazine 1,6,11-trione. AB - The title compound, C21H16N2O3, consists of an indazolone moiety, bearing a phenyl group, fused to a phthalazine ring system (r.m.s. deviation = 0.018 A). The phenyl ring is almost normal to the mean plane of the five-membered ring of the indazolone moiety, making a dihedral angle of 89.64 (7) degrees . The six membered ring of the indazolone moiety has an envelope conformation, with the central methyl-ene C atom as the flap. In the crystal, mol-ecules are linked via C-H?O hydrogen bonds, forming slabs parallel to the bc plane. The slabs are linked via C-H?pi and pi-pi inter-actions [the shortest inter-centroid distance involving rings of pyrazolo-phthalazine moieties is 3.6430 (8) A], forming a three-dimensional structure. PMID- 26870486 TI - Crystal structure of 4'-(2-meth-oxy-quinolin-3-yl)-1'-methyl-dispiro-[indan-2,2' pyrrolidine-3',3''-indoline]-1,3,2''-trione. AB - In the title compound, C30H23N3O4, the central 1-methyl-pyrrolidine ring adopts a twist conformation on the N-CH2 bond. The pyrrolidin-2-one ring of the indolin-2 one ring system also has a twist conformation on the C-C bond involving the spiro C atom and the carbonyl C atom. The five-membered ring of the indene-1,3-dione moiety has an envelope conformation with the spiro C atom as the flap. The quinoline ring system adopts an almost planar conformation (r.m.s. deviation = 0.04 A). The mean planes of the indolin-2-one ring system, the indene-1,3-dione ring system and the the quinoline ring system are inclined to the mean plane of the central 1-methyl-pyrrolidine ring by 77.97 (7), 86.98 (7) and 46.58 (6) degrees , respectively. In the crystal, mol-ecules are linked via N-H?N hydrogen bonds, forming chains along the b axis. The chains are linked via a number of C H?O hydrogen bonds, and C-H?pi and pi-pi inter-actions [inter-centroid distance = 3.7404 (9) A], forming a three-dimensional network. PMID- 26870487 TI - Crystal structure of (E)-(benzyl-idene)(pyridin-2-ylmeth-yl)amine. AB - In the title mol-ecule, C13H12N2, all non-H atoms, except for those of the pyridine ring, are essentially coplanar, with an r.m.s. deviation of 0.025 A. The mean plane of these atoms forms a dihedral angle of 80.98 (4) degrees with the pyridine ring. In the crystal, weak C-H?pi inter-actions link the mol-ecules, forming a three-dimensional network. PMID- 26870488 TI - Crystal structure of 1-mesityl-3-methyl-4-phenyl-1H-1,2,3-triazol-3-ium iodide. AB - In the cation of the title salt, C18H20N3 (+).I(-), the mesityl and phenyl rings are inclined to the central triazolium ring by 61.39 (16) and 30.99 (16) degrees , respectively, and to one another by 37.75 (15) degrees . In the crystal, mol ecules are linked via C-H?I hydrogen bonds, forming slabs parallel to the ab plane. Within the slabs there are weak pi-pi inter-actions present involving the mesityl and phenyl rings [inter-centroid distances are 3.8663 (18) and 3.8141 (18) A]. PMID- 26870489 TI - Crystal structure of 2-amino-3-cyano-4-(4-meth-oxy-phen-yl)-4H-1-benzo-thieno[3,2 b]pyran. AB - The three fused five- and six-membered rings in the title compound, C19H14N2O2S, are virtually coplanar, with the maximum deviation from the mean plane being 0.060 (1) A. This benzothieno[3,2-b]pyran ring system is nearly perpendic-ular to the plane of the 4-meth-oxy-phenyl ring, forming a dihedral angle of 83.65 (5) degrees . In the crystal, mol-ecules are linked by pairs of N-H?N hydrogen bonds into inversion dimers. The dimeric units are further connected by an N-H?O hydrogen bond into a tape running along the b axis. The tapes are linked together by C-H?N and pi-pi inter-actions [centroid-centroid distance = 3.7743 (8) A], forming a three-dimensional network. PMID- 26870490 TI - Crystal structure of N-[3-(di-methyl-amino)-prop-yl]-N',N',N'',N''-tetra-methyl-N (N,N,N',N'-tetra-methyl-form-amid-in-ium-yl)guanidinium bis-(tetra-phenyl borate). AB - In the title salt, C15H36N6 (2+).2C24H20B(-), the three N-C bond lengths in the central C3N unit of the bis-amidinium ion range between 1.388 (3) and 1.506 (3) A, indicating single- and double-bond character. Furthermore, four C-N bonds have double-bond character. Here, the bond lengths range from 1.319 (3) to 1.333 (3) A. Delocalization of the positive charges occurs in the N/C/N and C/N/C planes. The dihedral angle between both N/C/N planes is 70.5 (2) degrees . In the crystal, C-H?pi inter-actions between H atoms of the cation and the benzene rings of both tetra-phenyl-borate ions are present. The benzene rings form aromatic pockets, in which the bis-amidinium ion is embedded. This leads to the formation of a two-dimensional supra-molecular pattern along the ab plane. PMID- 26870491 TI - Crystal structure of 1-{(Z)-[(2E)-3-(4-chloro-phen-yl)-1-phenyl-prop-2-en-1-yl idene]amino}-3-ethyl-thio-urea. AB - In the title thio-semicarbazone compound, C18H18ClN3S, the CN3S residue is almost planar (r.m.s. deviation = 0.0031 A) and forms dihedral angles of 65.99 (7) and 34.60 (10) degrees with the phenyl and chloro-benzene rings, respectively; the dihedral angle between the aromatic rings is 85.13 (8) degrees . The conformation about the C=N bond is Z, and that about the C=C bonds is E. The imine N and ethyl N atoms are syn and are linked by an eth-yl-imine N-H?N hydrogen bond. This H atom also forms an inter-molecular hydrogen bond to the thione S atom, resulting in a supra-molecular helical chain propagating along the b axis. The chains are consolidated into a three-dimensional architecture by phenyl-C-H?Cl contacts and weak pi-pi inter-actions between centrosymmetrically related chloro-benzene rings [inter-centroid distance = 3.9127 (15) A]. PMID- 26870492 TI - Crystal structure of ethyl 2-(2-{1-[N-(4-bromo-phen-yl)-2-oxo-2-phenyl-acetamido] 2-tert-butyl-amino-2-oxo-ethyl}-1H-pyrrol-1-yl)acetate. AB - In the title compound, C28H30BrN3O5, there is an intra-molecular N-H?O hydrogen bond and an intra-molecular C-H?O hydrogen bond, both forming S(9) ring motifs. The planes of the 4-bromo-phenyl ring and the phenyl ring are inclined to that of the pyrrole ring by 48.05 (12) and 77.45 (14) degrees , respectively, and to one another by 56.25 (12) degrees . In the crystal, mol-ecules are linked via C-H?O hydrogen bonds and C-H?pi inter-actions, forming slabs parallel to (10-1). PMID- 26870493 TI - Crystal structure of 4-methyl-sulfanyl-2-(2H-tetra-zol-2-yl)pyrimidine. AB - The title compound, C6H6N6S, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The conformation of the two mol-ecules differs slightly. While the tetra-zole ring is inclined to the pyrim-idene ring by 5.48 (7) and 4.24 (7) degrees in mol-ecules A and B, respectively, the N-C-S-C torsion angles of the thio-methyl groups differ by ca 180 degrees . In the crystal, the A and B mol-ecules are linked via a C-H?N hydrogen bond. They stack along the b-axis direction forming columns within which there are weak pi-pi inter-actions present [shortest inter-centroid distance = 3.6933 (13) A]. PMID- 26870494 TI - Crystal structure of 2-(5-meth-oxy-1-benzo-furan-3-yl)acetic acid. AB - The benzo-furan residue in the title compound, C11H10O4, is essentially planar (the r.m.s. deviation for the nine non-H atoms = 0.011 A). While the meth-oxy group is coplanar with the fused ring system [C-C-O-C torsion angle = 3.1 (3) degrees ], the acetic acid residue occupies a position almost prime [C-C-C-C = 77.0 (2) degrees ]. In the crystal, centrosymmetrically related mol-ecules are linked by O-H?O hydrogen bonds to form eight-membered {?HOCO}2 synthons. The dimeric aggregates assemble into supra-molecular layers in the ab plane via benzene-C-H?O(ring) inter-actions. PMID- 26870495 TI - Crystal structure of methyl (2R,3S)-3-[(tert-butyl-sulfin-yl)amino]-2-fluoro-3 phenyl-propano-ate. AB - The title compound, C14H20FNO3S, contains two chiral carbon centres and the absolute configuration has been confirmed as (2R,3S). In the crystal, adjacent mol-ecules are linked by weak C-H?O hydrogen bonds, generating zigzag chains along the a-axis direction. PMID- 26870496 TI - Crystal structure of 1-(5-amino-2H-tetra-zol-2-yl)-2-methyl-propan-2-ol. AB - The title compound, C5H11N5O, crystallized with two independent mol-ecules in the asymmetric unit. The two mol-ecules differ in the orientation of the 2-methyl propan-2-ol unit, with the hy-droxy H atoms pointing in opposite directions. In the crystal, mol-ecules are linked via O-H?O and N-H?O hydrogen bonds, forming ribbons propagating along [10-1]. The ribbons are linked via N-H?N hydrogen bonds, forming a three-dimensional structure. PMID- 26870498 TI - Crystal structure of 2-bromo-3-di-methyl-amino-N,N,N',N',4-penta-methyl-4-(tri methyl-sil-yloxy)pent-2-eneamidinium bromide. AB - The reaction of the ortho-amide 1,1,1-tris-(di-methyl-amino)-4-methyl-4-(tri methyl-sil-yloxy)pent-2-yne with bromine in benzene, yields the title salt, C15H33BrN3OSi(+).Br(-). The C-N bond lengths in the amidinium unit are 1.319 (6) and 1.333 (6) A, indicating double-bond character, pointing towards charge delocalization within the NCN plane. The C-Br bond length of 1.926 (5) A is characteristic for a C-Br single bond. Additionally, there is a bromine-bromine inter-action [3.229 (3) A] present involving the anion and cation. In the crystal, weak C-H?Br inter-actions between the methyl H atoms of the cation and the bromide ions are present. PMID- 26870497 TI - Crystal structure of (Z)-7,8-di-chloro-4-(2-oxo-propyl-idene)-4,5-di-hydro-1H-1,5 benzodiazepin-2(3H)-one. AB - In the title compound, C12H10Cl2N2O2, the seven-membered heterocycle displays a half-chair conformation. The mean plane through the oxo-propyl-idene group makes a dihedral angle of 36.44 (9) degrees with the fused benzene ring. An intra molecular N-H?O hydrogen bond to close an S(6) loop is noted. An important feature of the mol-ecular packing are N-H?O hydrogen bonds that lead to the formation of helical supra-molecular chains along the b axis. PMID- 26870499 TI - Crystal structure of (1Z,2E)-cinnamaldehyde oxime. AB - The title compound, C9H9NO, crystallized with two independent mol-ecules (A and B) in the asymmetric unit. The conformation of the two mol-ecules differs slightly with the phenyl ring in mol-ecule A, forming a dihedral angle of 15.38 (12) degrees with the oxime group (O-N=C), compared to the corresponding angle of 26.29 (11) degrees in mol-ecule B. In the crystal, the A and B mol-ecules are linked head-to-head by O-H?N hydrogen bonds, forming -A-B-A-B- zigzag chains along [010]. Within the chains and between neighbouring chains there are C-H?pi inter-actions present, forming a three-dimensional structure. PMID- 26870500 TI - Crystal structure of 4,8-di-tert-butyl-6,6-di-chloro-13-ethyl-2,10-dimethyl-13,14 di-hydro-12H-dibenzo[d,i][1,3,7,2]dioxaza-silecine toluene 0.25-solvate. AB - The coordination polyhedron at the silicon atom in the title compound, C26H37Cl2NO2Si.0.25C7H8, is typical for penta-coordinated silicon derivatives and represents a slightly distorted trigonal bipyramid with an N atom and a Cl atom in the apical positions and the two O atoms and the other Cl atom occupying the equatorial sites. There are two independent mol-ecules in the asymmetric unit. The N-Si-Cl fragment in each is close to linear [178.24 (5) and 178.71 (5) degrees ], in good agreement with 4e-3c theory, as is the elongation of the apical bond lengths [Si-Cl = 2.1663 (7) and 2.1797 (7) A] in comparison with the equatorial bonds [Si-Cl = 2.0784 (7) and 2.0748 (7) A]. Orthogonal least-squares fitting of the two independent mol-ecules resulted in r.m.s. deviation of 0.017 A. The conformations of the two mol-ecules are almost the same, with corresponding torsion angles differing by less than 5.5 degrees . The toluene solvent mol-ecule is disordered about an inversion centre. PMID- 26870501 TI - Crystal structure of 3-bromo-9-ethyl-9H-carbazole. AB - In the title compound, C14H12BrN, the tricyclic ring system is essentially planar (r.m.s. deviation 0.026 A). The carbon atoms of the ethyl group deviate from the mean plane by 0.148 (9) (CH2) and 1.59 (1) A (CH3). In the crystal, H?pi contacts [2.698-2.898 A] shorter than the van der Waals contact distance of 3.70 A are observed. A scalable to gram quantities selective synthesis of mono-bromine substituted carbazole derivatives was developed. PMID- 26870502 TI - Crystal structure of 4-{2-[4-(di-methyl-amino)-phen-yl]diazen-1-yl}-1-methyl pyridinium iodide. AB - The mol-ecular geometry of the ionic title compound, C14H17N4 (+).I(-) or DAZOP(+).I(-), is essentially featureless. Regarding the crystal structure, in addition to the obvious cation-anion Coulombic inter-actions, the packing is mostly directed by non-covalent inter-actions involving both ring systems, as well as the iodide anion. It consists of cationic mol-ecules aligned along [101] and disposed in an anti-parallel fashion while linked into pi-bonded dimeric entities by a stacking contact involving symmetry-related phenyl rings, with a centroid-centroid distance of 3.468 (3) A and a slippage of 0.951 A. The dimers are, in addition, sustained by a number of C-H?I and I?pi (I?centroid = 3.876 A) inter-actions involving the anion. Finally, inter-dimeric contacts are of the C H?I and C-H?pi types. PMID- 26870503 TI - Crystal structure of (Z)-4-methylbenzyl 3-[1-(5-methylpyridin-2 yl)ethylidene]dithiocarbazate. AB - In the title di-thio-carbazate compound, C17H19N3S2, the central CN2S2 residue is essentially planar (r.m.s. deviation = 0.0288 A) and forms dihedral angles of 9.77 (8) and 77.47 (7) degrees with the substituted-pyridyl and p-tolyl rings, respectively, indicating a highly twisted mol-ecule; the dihedral angle between the rings is 85.56 (8) degrees . The configuration about the C=N bond is Z, which allows for the formation of an intra-molecular N-H?N(pyrid-yl) hydrogen bond. The packing features tolyl-methyl-C-H?N(imine), pyridyl-C-H?pi(tol-yl) and pi-pi inter-actions [between pyridyl rings with a distance = 3.7946 (13) A], which generates jagged supra-molecular layers that stack along the b axis with no directional inter-actions between them. PMID- 26870504 TI - Crystal structure of 4,6-di-chloro-5-methyl-pyrimidine. AB - The title compound, C5H4Cl2N2, is essentially planar with an r.m.s. deviation for all non-H atoms of 0.009 A. The largest deviation from the mean plane is 0.016 (4) A for an N atom. In the crystal, mol-ecules are linked by pairs of C-H?N hydrogen bonds, forming inversion dimers, enclosing an R (2) 2(6) ring motif. PMID- 26870505 TI - Crystal structure of 3-(di-ethyl-amino)-phenol. AB - The title compound, C10H15NO, has two mol-ecules in the asymmetric unit. Each mol ecule has a near-planar C8NO unit excluding H atoms and the terminal methyl groups on the di-ethyl-amino groups, with mean deviations from planarity of 0.036 and 0.063 A. In the crystal, hydrogen bonding leads to four-membered O-H?O-H?O H.. rings. No pi-pi inter-actions were observed in the structure. PMID- 26870506 TI - Crystal structure of N,N,N',N',N'',N''-hexa-methyl-guanidinium cyanate 1.5 hydrate. AB - The title hydrated salt, C7H18N3 (+).OCN(-).1.5H2O, was synthesized starting from N,N,N',N',N'',N''-hexa-methyl-guanidinium chloride by a twofold anion-exchange reaction. The asymmetric unit contains two cations, two cyanate anions and three water mol-ecules. One cation shows orientational disorder and two sets of N-atom positions were found related by a 60 degrees rotation, with an occupancy ratio of 0.852 (6):0.148 (6). The C-N bond lengths in both guanidin-ium ions range from 1.329 (2) to 1.358 (10) A, indicating double-bond character, pointing towards charge delocalization within the NCN planes. Strong O-H?N hydrogen bonds between the crystal water mol-ecules and the cyanate ions and strong O-H?O hydrogen bonds between the water mol-ecules are present, resulting in a two-dimensional hydrogen bonded network running parallel to the (001) plane. The hexa-methyl-guanidinium ions are packed in between the layers built up by water mol-ecules and cyanate ions. PMID- 26870507 TI - Crystal structure of N-[3-(di-methyl-aza-nium-yl)prop-yl]-N',N',N'',N''-tetra methyl-N-(N,N,N',N'-tetra-methyl-form-am-id-in-ium-yl)-guanidinium dibromide hydroxide monohydrate. AB - The asymmetric unit of the title hydrated salt, C15H37N6 (3+).2Br(-).OH(-).H2O, contains one cation, three partial-occupancy bromide ions, one hydroxide ion and one water mol-ecule. Refinement of the site-occupancy factors of the three disordered bromide ions converges with occupancies 0.701 (2), 0.831 (2) and 0.456 (2) summing to approximately two bromide ions per formula unit. The structure was refined as a two-component inversion twin with volume fractions 0.109 (8):0.891 (8) for the two domains. The central C3N unit of the bis-amidinium ion is linked to the aliphatic propyl chain by a C-N single bond. The other two bonds in this unit have double-bond character as have the four C-N bonds to the outer NMe2 groups. In contrast, the three C-N bonds to the central N atom of the (di-methyl aza-nium-yl)propyl group have single-bond character. Delocalization of the two positive charges occurs in the N/C/N and C/N/C planes, while the third positive charge is localized on the di-methyl-ammonium group. The crystal structure is stabilized by O-H?O, N-H?Br, O-H?Br and C-H?Br hydrogen bonds, forming a three dimensional network. PMID- 26870508 TI - Crystal structure of (E)-3-[4-(benzyl-idene-amino)-5-sulfanyl-idene-3-(p-tol-yl) 4,5-di-hydro-1H-1,2,4-triazol-1-yl]-3-(4-meth-oxy-phen-yl)-1-phenyl-propan-1-one. AB - The title compound, C32H28N4O2S, crystallizes as a racemate. In the mol-ecule, the bond-angle sum at the C atom of the sulfanyl-idene entity bound to the triazole ring is 360 degrees , with an annular N-C-N bond angle of 102.6 (2) degrees and two larger N-C-S angles of 127.3 (2) and 130.1 (2) degrees . The essentially planar 1,2,4-triazole ring (r.m.s. deviation = 0.013 A) is nearly perpendicular to the phenylpropanone and methoxyphenyl rings , making dihedral angles of 76.9 (2) and 85.2 (2) degrees , respectively and subtends dihedral angles of 17.6 (2) and 40.3 (2) degrees with the tolyl and benzylideneamino rings, respectively. There is no pi-pi stacking between the mol-ecules. The crystal packing is dominated by weak C-H?O and C-H?N inter-actions, leading to a three-dimensional network structure. An intra-molecular C-H?S inter-action also occurs. PMID- 26870509 TI - Crystal structure of (9S,10S)-10-eth-oxy-9-hy-droxy-6,6,9-trimethyl-3-pentyl 7,8,9,10-tetra-hydro-6H-benzo[c]chromen-1-yl 4-methyl-benzene-sulfonate. AB - In the structure of the title compound, C30H40O6S, the cyclo-hexene and heterocyclic rings are linked by a double bond. The cyclo-hexene ring has a half chair conformation (the methyl-ene group adjacent to the hy-droxy substituent lies above the remaining atoms) and the hy-droxy and eth-oxy groups have equatorial and bis-ectional dispositions, respectively. The heterocyclic ring has an envelope conformation (with the CMe2 C atom being the flap). The dihedral angle between the aromatic rings is 53.88 (10) degrees . A long intra-molecular C H?S inter-action is noted. In the mol-ecular packing, hy-droxy-O-H?O(sulfonate) hydrogen bonds lead to a helical chain along [010]. Connections between chains are of the type methyl-C-H?O(sulfonate) and lead to supra-molecular layers that lie parallel to (001). The studied crystal was an inversion twin. PMID- 26870510 TI - Crystal structure of piperazine-1,4-diium bis-(4-amino-benzene-sulfonate). AB - The asymmetric unit of the title salt, C4H12N2 (2+).2C6H6NO3S(-), consists of half a piperazindiium dication, located about an inversion centre, and a 4-amino benzene-sulfonate anion. The piperazine ring adopts a chair conformation. In the crystal, the cations and anions are linked via N-H?O and C-H?O hydrogen bonds, forming a three-dimensional framework. Within the framework there are C-H?pi inter-actions and the N-H?O hydrogen bonds result in the formation of R 4 (4)(22) and R 3 (4)(13) ring motifs. PMID- 26870511 TI - Crystal structure of N''-benzyl-N''-[3-(benzyl-dimethyl-aza-nium-yl)prop-yl] N,N,N',N'-tetra-methyl-guanidinium bis-(tetra-phenyl-borate). AB - In the crystal structure of the title salt, C24H38N4 (2+).2C24H20B(-), the C-N bond lengths in the central CN3 unit of the guanidinium ion are 1.3364 (13), 1.3407 (13) and 1.3539 (13) A, indicating partial double-bond character. The central C atom is bonded to the three N atoms in a nearly ideal trigonal-planar geometry and the positive charge is delocalized in the CN3 plane. The bonds between the N atoms and the terminal methyl groups of the guanidinium moiety and the four C-N bonds to the central N atom of the (benzyl-dimethyl-aza-nium yl)propyl group have single-bond character. In the crystal, C-H?pi inter-actions between the guanidin-ium H atoms and the phenyl C atoms of the tetra-phenyl borate ions are present, leading to the formation of a two-dimensional supra molecular pattern parallel to the ac plane. PMID- 26870512 TI - Crystal structure of methyl (2Z)-2-{[N-(2-formyl-phen-yl)-4-methyl-benzene sulfonamido]-meth-yl}-3-(4-meth-oxy-phen-yl)prop-2-enoate. AB - In the title compound, C26H25NO6S, the S atom shows a distorted tetra-hedral geometry, with O-S-O [119.46 (9) degrees ] and N-S-C [107.16 (7) degrees ] angles deviating from ideal tetra-hedral values, a fact attributed to the Thorpe-Ingold effect. The sulfonyl-bound phenyl ring forms dihedral angles of 41.1 (1) and 83.3 (1) degrees , respectively, with the formyl-phenyl and phenyl rings. The dihedral angle between formyl-phenyl and phenyl rings is 47.6 (1) degrees . The crystal packing features C-H?O hydrogen-bond inter-actions. PMID- 26870513 TI - Crystal structure of (E)-4,4,4-tri-fluoro-3-phenyl-but-2-enoic acid. AB - In the title compound, C10H7F3O2, the dihedral angle between the benzene ring and the ethyl-ene plane is 76.34 (11) degrees . In the crystal, O-H?O hydrogen bonds link the mol-ecules into C(4) chains propagating in [010]. PMID- 26870514 TI - Crystal structure of 15-(2-chloro-phen-yl)-6b-hy-droxy-17-methyl-6b,7,16,17-tetra hydro-7,14a-methanona-phtho[1',8':1,2,3]pyrrolo-[3',2':8,8a]azuleno[5,6 b]quinolin-14(15H)-one. AB - In the title compound, C34H25ClN2O2, the fused pyrrolidine ring adopts an envelope conformation with the N atom as the flap. The two adjacent cyclo-pentane rings also adopt envelope conformations. The mean plane of the pyrrolidine ring makes dihedral angles of 40.53 (10) and 80.23 (10) degrees with the mean planes of the cyclo-pentane rings. The dihedral angle between the mean planes of the cyclo-pentane rings is 46.71 (9) degrees . An intra-molecular O-H?N hydrogen bond is observed. In the crystal, mol-ecules are linked by C-H?O, C-H?N and C-H?pi inter-actions, forming a layer parallel to (10-2). PMID- 26870515 TI - Crystal structure of 5-(4-meth-oxy-phen-yl)-3-(4-methyl-phen-yl)-4,5-di-hydro-1H pyrazole-1-carbaldehyde. AB - In the title compound, C18H18N2O2, the pyrazole ring has a twisted conformation on the CH-CH2 bond. The tolyl ring and the 4-meth-oxy-phenyl ring are inclined to the mean plane of the pyrazole ring by 4.40 (9) and 86.22 (9) degrees , respectively, while the two aromatic rings are inclined to one another by 88.75 (9) degrees . In the crystal, mol-ecules are linked via bifurcated C-H?(O,O) hydrogen bonds and C-H?pi inter-actions, forming sheets lying parallel to the ab plane. PMID- 26870516 TI - Crystal structure of 1-{3-(4-methyl-phen-yl)-5-[(E)-2-phenyl-ethen-yl]-4,5-di hydro-1H-pyrazol-1-yl}ethan-1-one. AB - The title compound, C20H20N2O, was studied as a part of our work on pyrazoline derivatives. It represents a trans-isomer. The central pyrazoline ring adopts an envelope conformation with the asymmetric C atom having the largest deviation of 0.107 (1) A from the mean plane. It forms dihedral angles of 6.2 (1) and 86.4 (1) degrees with the adjacent p-tolyl and styrene groups, respectively. In the crystal, C-H?O inter-actions link mol-ecules into infinite chains along the c axis. PMID- 26870517 TI - Crystal structure of 4-methyl-N-{(E)-meth-yl[(3aR,8aS)-2-oxo-3,3a,8,8a-tetra hydro-2H-indeno-[1,2-d][1,3]oxazol-3-yl]-lambda(4)-sulfanyl-idene}benzene sulfonamide. AB - The formulation that the title compound, C18H18N2O4S2, adopts is a zwitterionic core with the charge separated to the sulfilimine S and N atoms and is supported by the two different S-N bond distances about the sulfinimine N atom [1.594 (2) and 1.631 (2) A, respectively] that are typical for such bonds. The notably unusual bond is S-N(oxazolidinone) [1.692 (2) A] that is longer than a typical S N bond [1.603 (18) A, Mogul analysis; Macrae et al. (2008 ?). J. Appl. Cryst. 41, 466-470]. The bond-angle sum about sulfilimine sulfur (308.35 degrees ) reflects the trigonal-pyramidal geometry of this atom. Two of the angles are less than 100 degrees . Despite the pyramidalization of this sulfur, there are no significant inter-molecular inter-actions, beyond usual van der Waals contacts, in the crystal packing. PMID- 26870518 TI - Crystal structure of 1,3-bis-{[4-(acetyl-sulfanyl)phenyl]ethynyl}azulene. AB - In the title compound, C30H20O2S2, the dihedral angles between the central azulene ring system (r.m.s. deviation = 0.039 A) and the pendant benzene rings are 28.96 (7) and 55.15 (7) degrees . The dihedral angles between the benzene rings and their attached acetyl-sulfanyl groups are 59.60 (10) and 84.79 (10) degrees . The expected pi-pi stacking inter-actions are not observed in the crystal structure; instead, the packing features C-H?O hydrogen bonds, which link the mol-ecules into C(12) [010] chains, which are supported by weak C-H?pi contacts. PMID- 26870519 TI - Crystal structure of N'-[(E)-(1S,3R)-(3-isopropyl-1-methyl-2-oxo-cyclo-pent yl)methyl-idene]-4-methyl-benzene-sulfono-hydrazide. AB - The title compound, C17H24N2O3S, was synthesized in order to determine the relative configuration of the corresponding beta-keto aldehyde. In the U-shaped mol-ecule, the five-membered ring approximates an envelope, with the methyl-ene C atom adjacent to the quaternary C atom being the flap, and the methyl and isopropyl substituents lying to the same side of the ring. The dihedral angles between the four nearly coplanar atoms of the five-membered ring and the flap and the aromatic ring are 35.74 (15) and 55.72 (9) degrees , respectively. The bond angles around the S atom are in the range from 103.26 (12) to 120.65 (14) degrees . In the crystal, mol-ecules are linked via N-H?O hydrogen bonds, forming a chain along the a axis. PMID- 26870520 TI - Crystal structure of (Z)-3-allyl-5-(4-methyl-benzyl-idene)-2-sulfanyl-idene-1,3 thia-zolidin-4-one. AB - In the title compound, C14H13NOS2, the atoms of the allyl group are disordered over two sets of sites, with an occupancy ratio of 0.559 (10):0.441 (10). The rhodanine ring makes a dihedral angle of 5.51 (12) degrees with the mean plane through the p-tolyl group. There are no specific inter-molecular inter-actions in the crystal packing. PMID- 26870521 TI - Crystal structure of ethyl 5-[3-(di-methyl-amino)-acrylo-yl]-2-{[(di-methyl amino)-methyl-idene]-amino}-4-methylthio-phene-3-carb-oxy-late. AB - In the title compound, C16H23N3O3S, the dihedral angles between the thio-phene ring and the almost planar di-methyl-amino-methyl-ene-amino (r.m.s. deviation = 0.005 A) and di-methyl-amino-acryloyl (r.m.s. deviation = 0.033 A) substituents are 6.99 (8) and 6.69 (7) degrees , respectively. The ester CO2 group subtends a dihedral angle of 44.92 (18) degrees with the thio-phene ring. An intra molecular C-H?O hydrogen bond generates an S(6) ring. In the crystal, inversion dimers linked by pairs of C-H?O hydrogen bonds generate R (2) 2(14) loops. In addition, a weak C-H?pi inter-action is observed. PMID- 26870522 TI - Crystal structure of 2-[2-phenyl-1-(phenyl-sulfon-yl)eth-yl]-1-phenyl-sulfonyl-1H indole. AB - In the title compound, C28H23NO4S2, the indole ring system (r.m.s. deviation = 0.007 A) subtends dihedral angles of 78.69 (13) and 38.97 (13) degrees with the planes of the N- and C-bonded sulfonyl-benzene rings, respectively, and these two benzene rings are inclined to each other at an angle of 65.45 (16) degrees . The methyl-ene-linked phenyl ring is twisted at an angle of 81.80 (13) degrees from the indole ring. The mol-ecular structure features two short intra-molecular C H?O contacts, which both generate S(6) rings. In the crystal, mol-ecules are linked by C-H?O hydrogen bonds and C-H?pi inter-actions, generating a three dimensional network. PMID- 26870523 TI - Crystal structure of 4-[(E)-(4-fluoro-benzyl-idene)amino]-3-methyl-1H-1,2,4 triazole-5(4H)-thione. AB - The title compound, C10H9FN4S, crystallizes with two mol-ecules (A and B) in the asymmetric unit. The dihedral angle between the planes of the trizole and fluoro benzene rings is 7.3 (3) degrees in mol-ecule A and 41.1 (3) degrees in mol ecule B. Mol-ecule A features an intra-molecular C-H?S hydrogen bond, which closes an S(6) ring. In the crystal, A+B dimers linked by pairs of N-H?S hydrogen bonds occur, generating R 2 (2)(8) loops. Weak pi-pi stacking contacts [centroid centroid separation = 3.739 (6) A] are also observed. PMID- 26870524 TI - Crystal structure of N-(1-acetyl-3-chloro-1H-indazol-6-yl)-4-meth-oxy-benzene sulfonamide. AB - In the title compound, C16H14ClN3O4S, the six-membered ring of the indazole group is connected to a sulfonamide group. The indazole system is essentially planar, with the greatest deviation from the mean plane being 0.007 (2) A. The dihedral angle between the two six-membered rings is 74.99 (9) degrees . The crystal structure exhibits inversion dimers in which mol-ecules are linked by pairs of N H?O and C-H?O hydrogen bonds. PMID- 26870525 TI - Crystal structure of (eth-oxy-ethyl-idene)di-methyl-aza-nium ethyl sulfate. AB - In the title salt, C6H14NO(+).C2H5SO4 (-), the C-N bond lengths in the cation are 1.2981 (14), 1.4658 (14) and 1.4707 (15) A, indicating double- and single-bond character, respectively. The C-O bond length of 1.3157 (13) A shows double-bond character, indicating charge delocalization within the NCO plane of the iminium ion. In the crystal, C-H?O hydrogen bonds between H atoms of the cations and O atoms of neighbouring ethyl sulfate anions are present, generating a three dimensional network. PMID- 26870526 TI - Crystal structure of ethyl 2-{2-[(1Z)-1-hy-droxy-3-(4-nitro-phen-yl)-3-oxoprop-1 en-1-yl]phen-oxy}acetate. AB - The title compound, C19H17NO7, crystallized in a ratio of about 6:4 of the two possible keto-enol forms. This was observed as disorder over the central C3H2O2 unit. The dihedral angle between the rings is 8.2 (2) degrees .The mol-ecules pack by C-H?O interactions in a layered fashion parallel to (-104). PMID- 26870527 TI - Crystal structure of (5Z)-5-(5-bromo-2-hy-droxy-benzyl-idene)-1,3-thia-zolidine 2,4-dione. AB - In the title compound, C10H6BrNO3S, the dihedral angle between the thia-zolidine ring (r.m.s. deviation = 0.014 A) and the benzene ring is 5.78 (14) degrees . The S atom of the heterocyclic ring is syn to the OH group attached to the benzene ring. In the crystal, inversion dimers linked by pairs of N-H?O hydrogen bonds generate R 2 (2)(8) loops. The dimers are linked into [001] ribbons by pairwise O H?O hydrogen bonds with R 2 (2)(18) motifs. There are no short contacts involving the Br atom. PMID- 26870528 TI - Crystal structure of 1-hy-droxy-2,2,6,6-tetra-methyl-piperidin-1-ium tri-fluoro methane-sulfonate. AB - In the cation of the title salt, C9H20NO(+).CF3O3S(-), the six-membered heterocyclic ring displays a chair conformation. In the crystal, centrosymmetric pairs of cations and anions are linked by N-H?O and O-H?O hydrogen bonds to form rings with a R 4 (4)(14) graph-set motif. PMID- 26870529 TI - Crystal structure of 2,5-bis-(di-phenyl-phosphan-yl)furan. AB - In the title compound, C28H22OP2, each of the P atoms has an almost perfect pyramidal geometry, with C-P-C angles varying from 100.63 (10) to 102.65 (9) degrees . In the crystal, neighbouring mol-ecules are linked via weak C-H?pi inter-actions, forming supra-molecular chains along the b-axis direction. PMID- 26870530 TI - Crystal structure of 1-(cyclo-pentyl-idene-amino)-3-(prop-2-en-1-yl)thio-urea. AB - In the title compound, C9H15N3S, the cyclo-pentyl ring adopts an envelope conformation with one of the methyl-ene C atoms as the flap. The thio semicarbazide fragment is almost planar (r.m.s. deviation = 0.038 A) and a short intra-molecular N-H?N contact occurs. In the crystal, mol-ecules are linked into helical (41 symmetry) chains propagating in [001] by N-H?N and N-H?S hydrogen bonds. A very weak C-H?S inter-action is also observed. PMID- 26870531 TI - Crystal structure of 2-(thio-phen-3-yl)ethyl pyrene-1-carboxyl-ate. AB - In the title compound, C23H16O2S, the thio-phene group is rotationally disordered into two fractions almost parallel to each other, with occupation factors of 0.523 (7) and 0.477 (7), and subtending dihedral angles of 10.5 (5) and 9.3 (5) degrees , respectively, to the thio-phene group. The mol-ecules are held together by weak C-H?O and C-H?pi hydrogen bonds, producing a laminar arrangement, which are further connected in a perpendicular fashion by S?pi contacts [S?centroid = 3.539 (8) and 3.497 (8) A]. In spite of the presence of the entended pyrene group, the structure does not present any parallel pi-pi stacking inter-actions. The structure was refined as an inversion twin. PMID- 26870532 TI - Crystal structure of (7-fluoro-2-oxo-2H-chromen-4-yl)methyl morpholine-4-carbodi thio-ate. AB - In the title compound, C15H14FNO3S2, the 2H-chromene ring system is close to being planar (r.m.s. deviation = 0.024 A) and the morpholine ring adopts a chair conformation. The dihedral angle between the 2H-chromene ring system and the morpholine ring (all atoms) is 88.21 (11) degrees . In the crystal, inversion dimers linked by pairs of very weak C-H?F hydrogen bonds generate R 2 (2)(8) loops; C-H?O hydrogen bonds connect the dimers into [010] chains. Weak aromatic pi-pi stacking inter-actions between the pyran rings of the chromene systems [centroid-centroid distance = 3.6940 (16) A] are also observed. PMID- 26870533 TI - Crystal structure of (2E)-1-(5-bromo-thio-phen-2-yl)-3-(2-chloro-phen-yl)prop-2 en-1-one. AB - In the title compound, C13H8BrClOS, the thienyl ring is not coplanar with the benzene ring, their planes forming a dihedral angle of 13.2 (4) degrees . In the crystal, mol-ecules stack along the a axis, with the inter-planar separation between thienyl rings and between benzene rings being 3.925 (6) A. The sample is an inversion twin. PMID- 26870534 TI - Crystal structure of 1-(2,4-di-nitro-phen-yl)-3,5-diphenyl-1H-pyrazole. AB - In the title mol-ecule, C21H14N4O4, the phenyl rings make dihedral angles of 39.61 (8) and 9.4 (1) degrees , respectively, with the central pyrazole ring. The dihedral angle between the pyrazole and di-nitro-phenyl rings is 46.95 (5) degrees . In the crystal, mol-ecules pack in helical stacks parallel to the a axis aided by weak C-H?O inter-actions. PMID- 26870535 TI - Crystal structure of 3-benzyl-1-[(cyclo-hexyl-idene)amino]-thio-urea. AB - The conformation of the title compound, C14H19N3S, is partially determined by an intra-molecular N-H?N hydro-gen-bond inter-action, although the N-H?N angle of 108 degrees is quite small. The cyclo-hexyl-idene ring has a chair conformation and its mean plane is inclined to the benzene ring by 46.30 (8) degrees . In the crystal, mol-ecules are linked by pairs of N-H?S hydrogen bonds, forming inversion dimers, with an R 2 (2)(8) ring motif. The dimers are reinforced by pairs of C-H?S hydrogen bonds, and are linked by further weak C-H?S hydrogen bonds, forming chains propagating along [100]. PMID- 26870536 TI - Crystal structure of 1,1'-[selanediyl-bis(4,1-phenyl-ene)]bis-(2-chloro-ethan-1 one). AB - In the title mol-ecule, C16H12Cl2O2Se, the C-Se-C angle is 100.05 (14) degrees , with the dihedral angle between the planes of the benzene rings being 69.92 (17) degrees . The average endocyclic angles (Se-Car-Car; ar = aromatic) facing the Se atom are 120.0 (3) and 119.4 (3) degrees . The Se atom is essentially coplanar with the benzene rings, with Se-Car-Car-Car torsion angles of -179.2 (3) and 179.7 (3) degrees . In the crystal, mol-ecules are linked via C-H?O hydrogen bonds forming chains propagating along the a-axis direction. The chains are linked via C-H?pi inter-actions, forming a three-dimensional network. PMID- 26870537 TI - Crystal structure of 3-(9H-carbazol-9-yl)-N'-[(E)-4-chloro-benzyl-idene]propano hydrazide. AB - In the title compound, C22H18ClN3O, the carbazole ring system is essentially planar (r.m.s deviation = 0.003 A), and makes a dihedral angle of 9.01 (8) degrees with the plane of the chloro-phenyl ring. In the crystal, neighbouring mol-ecules are linked into centrosymmetric R 2 (2)(8) dimers by pairs of N-H?O inter-actions and into a three-dimensional network by C-H?pi inter-actions. The dimers are arranged into layers parallel to (010). PMID- 26870538 TI - Crystal structure of ethyl 2,4-di-chloro-quinoline-3-carboxyl-ate. AB - In the crystal structure of the title compound, C12H9Cl2NO2, the mean planes through the quinoline and carboxyl-ate groups have r.m.s. deviations of 0.006 and 0.021 A, respectively, and form a dihedral angle of 87.06 (19) degrees . In the crystal, mol-ecules are linked via very weak C-H?O hydrogen bonds, forming chains, which propagate along the c-axis direction. PMID- 26870539 TI - Crystal structure of 4-formyl-2-nitro-phenyl 4-chloro-2-nitro-benzoate. AB - In the title compound, C14H7ClN2O7, the central ester moiety is essentially planar, with an r.m.s. deviation of 0.0113 A. The ester group is twisted away from the chloro- and formyl-substituted rings by 84.60 (9) and 88.55 (9) degrees , respectively. The crystal packing shows inter-molecular C-H?O inter-actions. These inter-actions generate R 2 (2)(20) and R 4 (4)(22) edge-fused rings parallel to (20-2). PMID- 26870540 TI - Crystal structure of (E)-N-[(2-meth-oxy-naphthalen-1-yl)methyl-idene]-3-nitro aniline. AB - In the title compound, C18H14N2O3, the dihedral angle between the naphthalene ring system and the benzene ring is 59.99 (13) degrees . A short intra-molecular C-H?N contact closes an S(6) ring. The nitro group is disordered over two orientations in a statistical ratio. In the crystal, weak C-H?O hydrogen bonds and very weak pi-pi stacking inter-actions [centroid-centroid separation = 3.9168 (17) A] are observed. PMID- 26870541 TI - Crystal structure of N-(2-hy-droxy-5-methyl-phen-yl)benzamide. AB - In the title compound, C14H13NO2, the mean plane of the non-H atoms of the central amide fragment C-N-C(=O)-C (r.m.s. deviation = 0.029 A) forms dihedral angles of 5.63 (6) and 10.20 (5) degrees with the phenyl and hy-droxy-phenyl rings, respectively. A short intra-molecular N-H?O contact is present. In the crystal, the mol-ecules are linked by O-H?O hydrogen bonds to generate C(7) chains along [100]. The chains are reinforced by weak C-H?O contacts, which together with the O-H?O bonds lead to R 2 (2)(7) loops. Very weak N-H?O inter actions link the mol-ecules into inversion dimers. PMID- 26870542 TI - Crystal structure of the bora-benzene-2,6-lutidine adduct. AB - In the title compound, C12H14BN, the complete mol-ecule is generated by a crystallographic twofold axis, with two C atoms, the B atom and the N atom lying on the rotation axis. The dihedral angle between the bora-benzene and pyridine rings is 81.20 (6) degrees . As well as dative electron donation from the N atom to the B atom [B-N = 1.5659 (18) A], the methyl substituents on the lutidine ring shield the B atom, which further stabilizes the mol-ecule. In the crystal, weak aromatic pi-pi stacking between the pyridine rings [centroid-centroid separation = 3.6268 (9) A] is observed, which generates [001] columns of mol-ecules. PMID- 26870543 TI - Crystal structure of 1-(1-methyl-1H-imidazol-2-yl)-4-phenyl-1H-1,2,3-triazole dihydrate. AB - The title compound, C12H11N5.2H2O, which crystallizes as a dihydrate, was obtained by Cu(I)-catalysed azide-alkyne cyclo-addition from 2-azido-1-methyl imidazole and phenyl-ethyne. The dihedral angles between the central triazole ring (r.m.s. deviation = 0.004 A) and the pendant imidazole (r.m.s. deviation = 0.006 A) and phenyl rings are 12.3 (2) and 2.54 (19) degrees , respectively. In the crystal, the water mol-ecules are connected into [010] chains by O-H?O hydrogen bonds, while O-H?N hydrogen bonds connect the water mol-ecules to the organic mol-ecules, generating corrugated (100) sheets. PMID- 26870544 TI - Crystal structure of 4-[(E)-(4-hy-droxy-benzyl-idene)amino]-1,5-dimethyl-2-phenyl 1H-pyrazol-3(2H)-one. AB - The asymmetric unit of the title compound, C18H17N3O2, comprises three independent mol-ecules (1, 2 and 3). In mol-ecule 1, the dihedral angles between the pyrazolone ring and the pendant phenyl and hydroxybenzene rings are 54.43 (6) and 28.72 (6) degrees , respectively. The corresponding data for mol-ecule 2 are 86.84 (6) and 25.69 (5) degrees , respectively, and for mol-ecule 3 are 47.41 (7) and 17.09 (7) degrees , respectively. The three mol-ecules feature an intra molecular C-H?O inter-action, which closes an S(6) ring in each case. In the crystal, mol-ecules are linked by O-H?O hydrogen bonds, which generate [100] chains incorporating all three asymmetric mol-ecules. Two weak C-H?O interactions connect three independent molecules to each other along the c-axis direction. PMID- 26870545 TI - Crystal structure of 2-amino-4-(4-chloro-phen-yl)-1-(4-methyl-phen-yl)-5-oxo 1,4,5,6,7,8-hexa-hydro-quinoline-3-carbo-nitrile. AB - In the title compound, C23H20ClN3O, each of the cyclo-hexene and 1,4-di-hydro pyridine rings of the 1,4,5,6,7,8-hexa-hydro-quinoline ring system adopts a twisted-boat conformation. The dihedral angle between the two benzene rings is 11.52 (7) degrees . In the crystal, mol-ecules are linked through a pair of amino nitrile N-H?N hydrogen bonds, forming inversion dimers. These assemble into a three-dimensional network via C-H?O and C-H?pi inter-actions. PMID- 26870546 TI - Crystal structure of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)meth-yl]-2-(thia-zol-4 yl)-1H-benzimidazole. AB - The benzimidazole ring in the title compound, C16H17N3O2S, is almost planar, with the greatest deviation from the mean plane being 0.032 (1) A. The fused-ring system makes dihedral angles of 19.91 (7) and 24.51 (8) degrees with the best plane through each of the thia-zol-4-yl and 1,3-dioxolan-4-yl rings, respectively; the latter exhibits an envelope conformation with the methyl-ene C atom being the flap. Finally, the thia-zol-4-yl ring makes a dihedral angle of 33.85 (9) degrees with the 1,3-dioxolan-4-yl ring. In the crystal, mol-ecules are connected by a pair of C-H?pi(imidazole) inter-actions to form centrosymmetric aggregates. PMID- 26870547 TI - Crystal structure of 2,6-bis-(2-hy-droxy-5-methyl-phen-yl)-4-phenyl-pyridinium bromide di-chloro-methane hemisolvate hemihydrate. AB - The asymmetric unit in the structure of the title compound, C25H22NO2 (+).Br ( ).0.5CH2Cl2.0.5H2O, comprises two pseudosymmetry-related cations, two bromide anions, a di-chloro-methane molecule and a water mol-ecule of solvation. The two independent cations are conformationally similar with the comparative dihedral angles between the central pyridine ring and the three benzene substituent rings being 3.0 (2), 36.4 (1) and 24.2 (1) degrees , and 3.7 (2), 36.5 (1) and 24.8 (1) degrees , respectively. In the crystal, the cations, anions and water mol-ecules are linked through O-H?O and O-H?Br hydrogen bonds, forming an insular unit. Within the cations there are also intra-molecular N-H?O hydrogen bonds. Adjacent centrosymmetrically related aggregates are linked by pi-pi stacking inter-actions between the pyridine ring and a benzene ring in both cations [ring-centroid separations = 3.525 (3) and 3.668 (3) A], forming chains extending across the ac diagonal. Voids between these chains are filled by dichloromethane molecules. PMID- 26870548 TI - Crystal structure of hexa-prop-2-en-1-yl 4,4',4'',4''',4'''',4''''' [1,3,5,2lambda(5),4lambda(5),6lambda(5)-tri-aza-triphosphinine-2,2,4,4,6,6-hexa yl-hexa-kis-(-oxy)]hexa-benzoate. AB - In the title compound, C60H54N3O18P3, the central phosphazene ring is essentially planar, with an r.m.s. deviation of the six fitted atoms of 0.068 A. The P-N bond lengths are within the narrow range 1.575 (2)-1.585 (2) A, indicating the electrons are delocalized within the ring. The two ethenyl benzoate substituents on each P atom are located up and down with respect to the plane of the central P3N3 ring. The atoms of two terminal propenyl groups are disordered over two sets of sites, with refined site-occupancy ratios of 0.249 (12):0.751 (12) and 0.476 (9):0.524 (9). No intermolecular interactions are observed. PMID- 26870549 TI - Crystal structure of 2-(2,3-di-methyl-anilino)-N'-[(1E)-2-hy-droxy-benzyl idene]benzohydrazide. AB - The asymmetric unit of the title compound, C22H21N3O2, consists of two independent mol-ecules (A and B) having differing conformations. The differences mainly concern the dihedral angles which the hy-droxy-phenyl and di-methyl-phenyl rings subtend to the central phenyl-ene ring, these being 30.16 (6) and 58.60 (6) degrees in mol-ecule A and 13.42 (7) and 60.31 (7) degrees in B. With the exception of the dimethyphenyl substituent, the conformations of the rest of each mol-ecule are largely determined by intra-molecular O-H?N and N-H?O hydrogen bonds. In the crystal, N-H?O hydrogen bonds link the mol-ecules into chains extending parallel to the a axis in which the types of mol-ecules alternate in an ...A...B...A...B... fashion. PMID- 26870550 TI - Crystal structure of 5,5'-bis-(di-methyl-amino)-N,N'-(3-methyl-3-aza-pentane-1,5 di-yl)di(naphthalene-1-sulfonamide). AB - In the title compound, C29H37N5O4S2, two arms substituted with dansyl derivatives are connected to a central tertiary amine, where the dihedral angle between the planes of two dansyl units is 56.39 (4) degrees . Each arm contains a sulfonamide functional group and both N-H groups in the compound are pointed to the same side. The central part of the mol-ecule is disordered over three sets of sites with a refined occupancy ratio of 0.547 (4):0.328 (4):0.125 (3). No intra molecular pi-pi or hydrogen-bonding inter-actions are observed. In the crystal, mol-ecules are linked via pairs of N-H?O inter-actions involving the same acceptor atom, forming inversion dimers. In addition, C-H?O inter-actions exist between molecules, providing further stabilization of dimers. PMID- 26870551 TI - Crystal structure of 1,2,3,4-di-O-methyl-ene-alpha-d-galacto-pyran-ose. AB - The title compound, C8H12O6, was synthesized by de-acetyl-ation of 6-acetyl 1,2,3,4-di-O-methyl-ene-alpha-d-galactose with sodium methoxide. The central part of the mol-ecule consists of a six-membered C5O pyran-ose ring with a twist-boat conformation. Both fused dioxolane rings adopt an envelope conformation with C and O atoms as the flap. In the crystal, O-H?O and C-H?O hydrogen bonds are present between adjacent mol-ecules, generating a three-dimensional network. PMID- 26870552 TI - Crystal structure of 2-[9-(2-hy-droxy-phen-yl)-1,8-dioxo-1,2,3,4,5,6,7,8,9,10 deca-hydro-acridin-10-yl]acetic acid. AB - The title compound, C21H21NO5, crystallizes with two mol-ecules in the asymmetric unit. In each mol-ecule, the central 1,4-di-hydro-pyridine ring adopts a shallow sofa conformations (with the C atom bearing the phenol ring as the flap), whereas the pendant cyclo-hexene rings both have twisted-boat conformations. Each mol ecule features an intra-molecular O-H?O hydrogen bond, which closes an S(8) ring. In the crystal, the mol-ecules are linked by O-H?O, C-H?O and C-H?pi inter actions, forming a three-dimensional network. PMID- 26870553 TI - Crystal structure of (5Z)-5-(2-hy-droxy-benzyl-idene)-1,3-thia-zolidine-2,4 dione. AB - The title compound, C10H7NO3S, crystallizes with four independent mol-ecules in the asymmetric unit with slightly different conformations; the dihedral angles between the six- and five-membered rings are 2.6 (1), 1.09 (9), 8.6 (1) and 6.2 (1) degrees . In the crystal, mol-ecules are linked by O-H?O and N-H?O hydrogen bonds, forming sheets lying parallel to (101). PMID- 26870554 TI - Crystal structure of N'-[bis-(ethyl-sulfan-yl)methyl-idene]-2-hy-droxy-4-meth-oxy benzohydrazide. AB - In the title compound, C13H18N2O3S2, the amide group is in the plane of the benzoyl ring with a C-N-N-C torsion angle of 177.63 (12) degrees . The two di thio-ate groups are in an anti conformation [torsion angles = 173.68 (8) and 9.98 (10) degrees ]. An intra-molecular N-H?O hydrogen bond is observed. In the crystal, an O-H?O hydrogen bond and a weak C-H?O contact involving the same acceptor atom generate an S(6) ring motif and give rise to chains along [010]. PMID- 26870555 TI - Crystal structure of phenyl N-(4-nitro-phen-yl)carbamate. AB - The asymmetric unit of the title compound, C13H10N2O4, contains two independent mol-ecules (A and B). The dihedral angle between the aromatic rings is 48.18 (14) degrees in mol-ecule A and 45.81 (14) degrees in mol-ecule B. The mean plane of the carbamate N-C(=O)-O group is twisted slightly from the attached benzene and phenyl rings, making respective dihedral angles of 12.97 (13) and 60.93 (14) degrees in A, and 23.11 (14) and 59.10 (14) degrees in B. In the crystal, A and B mol-ecules are arranged alternately through N-H?O hydrogen bonds and C-H?pi inter-actions, forming chains along the a axis. The chains are further linked by C-H?O hydrogen bonds into a double-chain structure. PMID- 26870556 TI - Crystal structure of 5-(5,6-di-hydro-benzo[4,5]imidazo[1,2-c]quinazolin-6-yl)-2 meth-oxy-phenol. AB - In the mol-ecule of the title compound, C21H17N3O2, the 5,6-di-hydro benzimidazo[1,2-c]quinazoline moiety is disordered over two orientations about a pseudo-mirror plane, with a refined occupancy ratio of 0.863 (2):0.137 (2). The dihedral angles formed by the benzimidazole ring system and the benzene ring of the quinazoline group are 14.28 (5) and 4.7 (3) degrees for the major and minor disorder components, respectively. An intra-molecular O-H?O hydrogen bond is present. In the crystal, mol-ecules are linked by O-H?N hydrogen bonds, forming chains running parallel to [10-1]. PMID- 26870557 TI - Crystal structure of 1-bromo-4-methane-sulfonyl-2,3-di-methyl-benzene. AB - The title compound, C9H11BrO2S, is an important inter-mediate in the synthesis of the herbicide Topramezone. In the crystal, there are weak inter-molecular Br?O inter-actions of 3.286 (4) A. The dihedral angle between the plane of the benzene ring and that defined by the O-S-O atoms of the methane-sulfonyl group is 49.06 (3) degrees . PMID- 26870558 TI - Crystal structure of 3-benzyl-1-[(1,2,3,4-tetra-hydro-naphthalen-1-yl idene)amino]-thio-urea. AB - In the title compound, C18H19N3S, the dihedral angle between the planes of the benzene rings is 58.63 (8) degrees . The six-membered ring bonded to the thio semicarbazide group (r.m.s. deviation = 0.038 A) adopts a sofa conformation, with one of the methyl-ene-group C atoms as the flap. A short intra-molecular N-H?N contact is observed. In the crystal, mol-ecules are linked by weak N-H?S inter actions to generate C(4) chains propagating in the [010] direction, with adjacent mol-ecules related by glide symmetry. PMID- 26870559 TI - Crystal structure of 3-(prop-2-en-1-yl)-1-{[(1E)-1,2,3,4-tetra-hydro-naphthalen-1 yl-idene]amino}-thio-urea. AB - In the title compound, C14H17N3S, the dihedral angle between the planes of the benzene ring and the thio-semicarbazone group (r.m.s. deviation = 0.031 A) is 8.45 (4) degrees . A short intra-molcular N-H?N contact is seen. In the crystal, weak N-H?S hydrogen bonds connect the mol-ecules into C(4) chains propagating in the [010] direction, with adjacent mol-ecules in the chain related by 21 screw axis symmetry. PMID- 26870560 TI - Crystal structure of 2-butyl-sulfanyl-4,6-bis-[(E)-4-(di-methyl-amino)-styr yl]pyrimidine. AB - In the title compound, C28H34N4S, the dihedral angles between the pyrimidine ring and the pendant 4-(di-methyl-amino)-benzene rings are 14.20 (5) and 14.56 (4) degrees . The butyl side chain adopts an anti conformation [C-C-C-C = -171.53 (13) degrees ]. No directional inter-actions beyond van der Waals contacts occur in the crystal structure The title mol-ecule has a D-A-D structure, in which the pyrimidine ring is the electron-withdrawing part and the 4-(di-methyl-amino) benzene rings are the electron-donating parts. PMID- 26870561 TI - Crystal structure of 2-(4-meth-oxy-phen-yl)-6-nitro-imidazo[1,2-a]pyridine-3 carbaldehyde. AB - In the title compound, C15H11N3O4, the imidazo[1,2-a] pyridine ring system is almost planar [r.m.s. deviation = 0.028 (2) A]. Its mean plane makes dihedral angles of 33.92 (7) and 34.56 (6) degrees with the meth-oxy-phenyl ring and the nitro group, respectively. The cohesion of the crystal structure is ensured by C H?N and C-H?O hydrogen bonds, forming layers almost parallel to the ac plane. PMID- 26870563 TI - Crystal structure of (E)-3-(4-hy-droxy-benz-yl)-4-{[4-(methyl-sulfan-yl)benzyl idene]amino}-1H-1,2,4-triazole-5(4H)-thione. AB - In the title compound, C17H16N4OS2, the triazole and methyl-thio-benzyl-idene rings are nearly coplanar, making a dihedral angle of 6.52 (12) degrees . An intra-molecular C-H?S hydrogen bond forms an S(6) ring motif. The hy-droxy-benzyl ring is almost normal to the triazole and methyl-thio-benzyl-idene rings, making dihedral angles of 78.56 (12) and 84.79 (11) degrees , respectively. In the crystal, mol-ecules are linked through O-H?N and N-H?O hydrogen bonds, forming layers parallel to the ac plane. The layers are linked via C-H?N hydrogen bonds, forming a three-dimensional structure. In addition, a short pi-pi inter-action is observed [inter-centroid distance = 3.764 (3) A], involving inversion-related methyl-thio-benzyl-idene rings. PMID- 26870562 TI - Crystal structure of 4-(4-meth-oxy-phen-yl)-4',4'-dimethyl-3-p-tolyl-3',4'-di hydro-1'H,3H-spiro-[isoxazole-5,2'-naphthalen]-1'-one. AB - In the title compound, C28H27NO3, the cyclo-hexa-none and isoxazole rings have envelope conformations, with the methyl-ene and spiro C atoms as the flaps, respectively. The mean plane of the isoxazole ring is inclined slightly to the p tolyl ring, making a dihedral angle of 14.20 (9) degrees , and is nearly perpendicular to the mean plane through the tetra-lone moiety and to the meth-oxy phenyl ring [dihedral angles = 83.41 (8) and 72.12 (9) degrees , respectively]. The crystal packing is stabilized mainly by van der Waals forces. PMID- 26870564 TI - Crystal structure of (1-eth-oxy-ethyl-idene)di-methyl-aza-nium tetra-phenyl borate. AB - In the cation of the title salt, C6H14NO(+).C24H20B(-), the C-N bond lengths are 1.297 (2), 1.464 (2) and 1.468 (2) A, indicating double- and single-bond character, respectively. The C-O bond length of 1.309 (2) A shows double-bond character, pointing towards charge delocalization within the NCO plane of the iminium ion. In the crystal, C-H?pi inter-actions between the iminium H atoms and the phenyl C atoms of the anion are present. The phenyl rings form aromatic pockets, in which the iminium ions are embedded. PMID- 26870565 TI - Crystal structure of 4,4'-[(1,3,5,7-tetra-oxo-1,3,3a,4,4a,5,7,7a,8,8a-deca-hydro 4,8-etheno-pyrrolo-[3,4-f]iso-indole-2,6-di-yl)bis-(methyl-ene)]bis-(pyridin-1 ium) dinitrate. AB - In the title salt, C24H22N4O4 (2+).2NO3 (-), the cation is U-shaped with the two iso-indole dione rings inclined to one another by 60.41 (13) degrees , while the two outer pyridine rings are inclined to one another by 2.77 (12) degrees . The dihedral angles between the pyridine ring and the adjacent iso-indole dione ring are 71.82 (12) and 86.44 (13) degrees . In the crystal, each nitrate anion is linked to a protonated pyridine ring by N-H?O hydrogen bonds. These units are linked by a series of C-H?O hydrogen bonds, forming a three-dimensional structure. PMID- 26870566 TI - Crystal structure of ethyl 2-[9-(5-bromo-2-hy-droxy-phen-yl)-1,8-dioxo 1,2,3,4,5,6,7,8,9,10-deca-hydro-acridin-10-yl]acetate. AB - In the title compound, C23H24BrNO5, the central 1,4-di-hydro-pyridine ring of the 1,2,3,4,5,6,7,8,9,10-deca-hydro-acridine ring system adopts a half-chair conformation. The two cyclo-hexene rings fused to the central ring both have a twisted-boat conformation. The mean planes of the bromo-hydroxy-phenyl ring and the major and minor components of the disordered ethyl amino-acetate moiety make dihedral angles of 78.99 (12), 85.9 (2) and 88.3 (9) degrees , respectively, with the 1,4-di-hydro-pyridine ring. The terminal ethyl group of the ethyl amino acetate moiety is disordered over two sets of sites with refined occupancies of 0.768 (17) and 0.232 (17). The mol-ecular conformation is stabilized by an intra molecular O-H?O hydrogen bond, forming an S(8) ring motif. In the crystal, C-H?O hydrogen bonds connect the mol-ecules into layers parallel to (001), enclosing R 1 (2)(7) ring motifs. PMID- 26870567 TI - Crystal structure of 4-bromo-2-(1H-imidazo[4,5-b]pyridin-2-yl)phenol. AB - In the title compound, C12H8BrN3O, the 4-bromo-phenol ring is coplanar with the planar imidazo[4,5-b]pyridine moiety (r.m.s deviation = 0.015 A), making a dihedral angle of 1.8 (2) degrees . There is an intra-molecular O-H?N hydrogen bond forming an S(6) ring motif. In the crystal, mol-ecules are linked via N-H?N and O-H?Br hydrogen bonds, forming undulating sheets parallel to (10-2). The sheets are linked by pi-pi inter-actions [inter-centroid distance = 3.7680 (17) A], involving inversion-related mol-ecules, forming a three-dimensional structure. PMID- 26870568 TI - Crystal structure of 6-de-oxy-alpha-l-psico-furan-ose. AB - The title compound, C6H12O5, was crystallized from an aqueous solution of 6-de oxy-l-psicose (6-de-oxy-l-allulose, (3S,4S,5S)-1,3,4,5-tetra-hydroxy-hexan-2 one), and the mol-ecule was confirmed as alpha-furan-ose with a (3) T 4 (or E 4) conformation, which is a predominant tautomer in solution. This five-membered furan-ose ring structure is the second example in the field of the 6-de-oxy ketohexose family. The cell volume of the title compound [742.67 (7) A(3), Z = 4 at room temperature] is only 1.4% smaller than that of beta-d-psico-pyran-ose, C6H12O6 (753.056 A(3), Z = 4 at room temperature). PMID- 26870569 TI - Crystal structure of 4-{[(2,4-di-hydroxy-benzyl-idene)amino]-meth-yl}cyclo-hexane carb-oxy-lic acid. AB - In the title compound, C15H19NO4, the cyclo-hexyl ring adopts a chair conformation with both exocyclic C-C bonds in equatorial orientations. The dihedral angle between the basal plane of cyclo-hexyl ring and the 2,4-di-hydroxy benzaldehyde moiety is 84.13 (13) degrees . An intra-molecular O-H?N hydrogen bonds closes an S(6) ring. In the crystal, Oc-H?Op (c = carb-oxy-lic acid, p = phenol) hydrogen bonds link the mol-ecules into [100] C(13) chains whereas an Op H?Oc hydrogen bond generates [101] C(15) chains. Together, these bonds generate (010) sheets incorporating R 2 (2)(20) loops. Weak C-H?O and C-H?pi inter-actions also occur. PMID- 26870570 TI - Crystal structure of (4-meth-oxy-phen-yl)[(4-meth-oxy-phen-yl)phospho nato]dioxidophosphate(1-) 2-amino-6-benzyl-3-eth-oxy-carbon-yl-4,5,6,7-tetra hydro-thieno[2,3-c]pyridin-6-ium. AB - The asymmetric unit of the title mol-ecular salt, C17H21N2O2S(+).C14H15O7P2 (-), comprises two cations and two anions. Each cation features an intra-molecular N H?O hydrogen bond, which closes an S(6) ring; in each case the hydro-pyridine ring adopts a half-chair conformation. In the anions, the dihedral angles between the aromatic rings are 64.1 (2) and 54.9 (2) degrees . In each case, the diphosphate groups are close to eclipsed [C-P?P-C pseudo-torsion angles = 11.6 (2) and -19.3 (2) degrees ]. One of the meth-oxy groups in each anion is disordered over two orientations in a 0.539 (18):0.461 (18) ratio in one anion and 0.82 (2):0.18 (2) in the other. In the crystal, O-H?O and N-H?O hydrogen bonds link the components into [100] chains. Numerous C-H?O inter-actions cross link the chains into a three-dimensional network. PMID- 26870571 TI - Crystal structure of 4-benzyl-2H-benzo[b][1,4]thia-zin-3(4H)-one. AB - In the title compound, C15H13NOS, the thia-zine ring adopts a twisted boat conformation and the dihedral angle between the aromatic rings is 86.54 (4) degrees . In the crystal, mol-ecules are linked by weak C-H?O inter-actions, resulting in chains along [010]. PMID- 26870572 TI - Crystal structure of catena-poly[N,N,N',N'-tetra-methyl-guanidinium [(chlorido cadmate)-di-MU-chlorido]]. AB - In the structure of the title salt, {(C5H14N3)[CdCl3]} n , the Cd(II) atom of the complex anion is five-coordinated by one terminal and four bridging Cl atoms. The corresponding coordination polyhedron is a distorted trigonal bipyramid, with Cd Cl distances in the range 2.4829 (4)-2.6402 (4) A. The bipyramids are condensed into a polyanionic zigzag chain extending parallel to [101]. The tetra-methyl guanidinium cations are situated between the polyanionic chains and are linked to them through N-H?Cl hydrogen bonds, forming a layered network parallel to (010). PMID- 26870573 TI - Crystal structure of aqua-bis-(hepta-fluoro-butano-ato-kappaO)(1,10' phenanthroline-kappa(2) N,N')copper(II). AB - The title compound, [Cu(C4F7O2)2(C12H8N2)(H2O)], is mononuclear and contains a penta-coordinated Cu(II) ion. The geometry of Cu(II) ion can be described as distorted square-pyramidal with two O atoms of two butano-ate anions and two N atoms of the o-phenanthroline ligand occupying the basal plane, and a water O atom located at the axial position. In the crystal, C-H?(O,F) and O-H?(O,F) hydrogen bonds and pi-pi inter-actions [centroid-to-centroid distance 3.533 (2) A] link the mol-ecules into a three-dimensional supra-molecular structure. PMID- 26870574 TI - Crystal structures of ethyl 6-(4-methyl-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate and ethyl 6-(4-fluoro-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate. AB - The crystal structures of two chromone derivatives, viz. ethyl 6-(4-methyl-phen yl)-4-oxo-4H-chromene-2-carboxyl-ate, C19H16O4, (1), and ethyl 6-(4-fluoro-phen yl)-4-oxo-4H-chromene-2-carboxyl-ate C18H13FO4, (2), have been determined: (1) crystallizes with two mol-ecules in the asymmetric unit. A comparison of the dihedral angles beween the mean planes of the central chromone core with those of the substituents, an ethyl ester moiety at the 2-position and a para-substituted phenyl ring at the 6-position shows that each mol-ecule differs significantly from the others, even the two independent mol-ecules (a and b) of (1). In all three mol-ecules, the carbonyl groups of the chromone and the carboxyl-ate are trans-related. The supra-molecular structure of (1) involves only weak C-H?pi inter-actions between H atoms of the substituent phenyl group and the phenyl group, which link mol-ecules into a chain of alternating mol-ecules a and b, and weak pi-pi stacking inter-actions between the chromone units. The packing in (2) involves C-H?O inter-actions, which form a network of two inter-secting ladders involving the carbonyl atom of the carboxyl-ate group as the acceptor for H atoms at the 7-position of the chromone ring and from an ortho-H atom of the exocyclic benzene ring. The carbonyl atom of the chromone acts as an acceptor from a meta-H atom of the exocyclic benzene ring. pi-pi inter-actions stack the mol-ecules by unit translation along the a axis. PMID- 26870575 TI - Crystal structure of MU-fluorido-bis-{(eta(4)-cyclo-octa-diene)[hexa-fluorido anti-monato(V)]platinum(II)} hexa-fluorido-anti-monate(V) hydrogen fluoride 0.75 solvate. AB - In the complex cation of the binuclear solvated title salt, [Pt2F(SbF6)2(C8H12)2]SbF6.0.75HF, an F atom bridges the two platinum(II) atoms with a bond angle of 123.3 (2) degrees . The corresponding Pt-F bond lengths are in the range of other fluorine-bridged binuclear platinum(II) complexes. Two of the three SbF6 (-) anions each coordinate with one F atom to one platinum(II) atom. Including the eta(4)-bound cyclo-octa-diene (COD) ligands, the overall coordination sphere of each platinum(II) atom is square-planar. The third SbF6 ( ) anion is not bound to the complex. Hydrogen fluoride is present in the crystal structure as a solvent disordered over three positions, each with an occupancy of 0.25. F?F distances of 2.5512 (7), 2.6076 (8) and 3.2215 (10) A to surrounding SbF6 (-) anions are indicative of F-H?F hydrogen-bonding inter-actions although no H atoms could be localized for the disordered solvent mol-ecules. The resulting hydrogen-bonded network is three-dimensional. PMID- 26870576 TI - Crystal structure of the coordination compound of triiodidomethyltin(IV) with 2,2'-bi-pyridine, MeSnI3.bipy. AB - The title compound, (2,2'-bi-pyridine-kappa(2) N,N')tri-iodido-meth-yltin(IV), [Sn(CH3)I3(C10H8N2)], crystallizing in the non-centrosymmetric ortho-rhom-bic space group Pca21 as an inversion twin, represents one of the few structurally characterized coordination compounds of an organotin(IV) trihalide with 2,2' biypridine. Its distorted octa-hedral geometry shows a meridional arrangement of the I atoms and the methyl group is in-plane with the five-membered chelate ring. Asymmetric bonding of the biypridine ligand to the tin(IV) atom is reflected by different Sn-N bond lengths [2.268 (4) A versus 2.293 (4) A] and caused by the static trans effect of the methyl group. Sn-I bond lengths show some differences with respect to their orientation to the methyl group or the bi-pyridine ligand, respectively. Angular distortions in the coordination sphere of the Sn(IV) atom mainly arise from the large I atoms. Distortion of the 2,2'-bi-pyridine ligand as a result of its coordination to the Sn(IV) atom are described by the twisting angle of 2.5 (2) degrees between the least-squares planes of the two pyridine rings, as well as by the angle of 6.2 (2) degrees between the two lines through the pyridine-connecting C atoms and the para-orientated C atoms. Directional inter-molecular inter-actions are restricted to weak I?H van der Waals contacts. PMID- 26870577 TI - Crystal structure of poly[di-aqua-(MU-2-carb-oxy-acetato-kappa(3) O,O':O'')(2 carb-oxy-acetato-kappaO)di-MU-chlorido-dicobalt(II)]. AB - The asymmetric unit of the title polymer, [Co2(C3H3O4)2Cl2(H2O)2] n , comprises one Co(II) atom, one water mol-ecule, one singly deprotonated malonic acid mol ecule (HMal(-); systematic name 2-carb-oxy-acetate) and one Cl(-) anion. The Co(II) atom is octa-hedrally coordinated by the O atom of a water mol-ecule, by one terminally bound carboxyl-ate O atom of an HMal(-) anion and by two O atoms of a chelating HMal(-) anion, as well as by two Cl(-) anions. The Cl(-) anions bridge two Co(II) atoms, forming a centrosymmetric Co2Cl2 core. Each malonate ligand is involved in the formation of six-membered chelate rings involving one Co(II) atom of the dinuclear unit and at the same time is coordinating to another Co(II) atom of a neighbouring dinuclear unit in a bridging mode. The combination of chelating and bridging coordination modes leads to the formation of a two dimensional coordination polymer extending parallel to (001). Within a layer, O Hwater?Cl and O-Hwater?O hydrogen bonds are present. Adjacent layers are linked through O-H?O=C hydrogen bonds involving the carb-oxy-lic acid OH and carbonyl groups. PMID- 26870578 TI - Crystal structures of [Ln(NO3)3(MU2-bpydo)2], where Ln = Ce, Pr or Nd, and bpydo = 4,4'-bi-pyridine N,N'-dioxide: layered coordination networks containing 4(4) grids. AB - Three isostructural coordination networks of Ce, Pr, and Nd nitrate with 4,4'-bi pyridine N,N'-dioxide (bpydo) are reported, namely poly[[tris-(nitrato-kappa(2) O,O')cerium(III)]-bis-(MU2-4,4'-bi-pyridine N,N'-dioxide-kappa(2) N:N')], [Ce(NO3)3(C10H8N2O2)2], poly[[tris-(nitrato-kappa(2) O,O')praeseodymium(III)]-bis (MU2-4,4'-bi-pyridine N,N'-dioxide-kappa(2) N:N')], [Pr(NO3)3(C10H8N2O2)2], and poly[[tris(nitrato-kappa(2) O,O')neodymium(III)]-bis-(MU2-4,4'-bi-pyridine N,N' dioxide-kappa(2) N:N'], [Nd(NO3)3(C10H8N2O2)2]. All three compounds are isostructural to the previously reported La analogue. The asymmetric unit of [Ln(NO3)3(MU2-bpydo)2] contains one lanthanide cation, two bpydo ligands, and three nitrate anions. Both bpydo ligands act as end-to-end MU2-bridges and display nearly ideal cis and gauche conformations, respectively. The bpydo ligands link the ten-coordinate Ln (III) cations, forming inter-digitating 4(4) grid-like layers extending parallel to (-101), where inter-digitation of layers is promoted by C-H?O inter-actions between nitrate anions and bpydo ligands. The inter-digitated layers are linked to sets of neighboring layers via further C-H?O and pi-pi inter-actions. PMID- 26870579 TI - Crystal structure of ethyl (1RS,6SR)-4-(2-methyl-1H-imidazol-4-yl)-2-oxo-6-(2,3,5 tri-chloro-phen-yl)cyclo-hex-3-ene-1-carboxyl-ate. AB - The title compound, C19H17Cl3N2O3, has been prepared in a cyclo-condensation reaction between 2,3,5-tri-chloro-benzaldehye and 4-acetyl-2-methyl-1H-imidazole. The cyclo-hexenone ring adopts an envelope conformation with the C atom substituted by the tri-chloro-phenyl ring as the flap. The mutually trans ester and aryl substituents both occupy equatorial sites. In the crystal, a combination of N-H?O and C-H?N hydrogen bonds links the mol-ecules into ribbons of edge-fused centrosymmetric rings, which enclose R 2 (2)(14) and R 4 (4)(16) alternate ring motifs, propagating along the b-axis direction. PMID- 26870580 TI - Crystal structures of three complexes of zinc chloride with tri-tert-butyl phosphane. AB - Under anhydrous conditions and in the absence of a Lewis-base solvent, a zinc chloride complex with tri-tert-butyl-phosphane as the MU-bridged dimer is formed, viz. di-MU-chlorido-bis-[chlorido-bis-(tri-tert-butyl-phosphane)zinc], [ZnCl4(C12H27P)2], (1), which features a nearly square-shaped (ZnCl)2 cyclic core and whose Cl atoms inter-act weakly with C-H groups on the phosphane ligand. In the presence of THF, monomeric di-chlorido-(tetra-hydro-furan-kappaO)(tri-tert butyl-phosphane-kappaP)zinc, [ZnCl2(C4H8O)(C12H27P)] or [P(tBu3)(THF)ZnCl2], (2), is formed. This slightly distorted tetra-hedral Zn complex has weak C-H?Cl inter actions between the Cl atoms and phosphane and THF C-H groups. Under ambient conditions, the hydrolysed complex tri-tert-butyl-phospho-nium aqua-tri-chlorido zincate 1,2-di-chloro-ethane monosolvate, (C12H28P)[ZnCl3(H2O)].C2H4Cl2 or [HPtBu3](+) [(H2O)ZnCl3](-).C2H4Cl2, (3), is formed. This complex forms chains of [(H2O)ZnCl3](-) anions from hydrogen-bonding inter-actions between the water H atoms and Cl atoms that propagate along the b axis. PMID- 26870581 TI - Crystal structure of the thermochromic bis-(di-ethyl-ammonium) tetra-chlorido cuprate(II) complex. AB - In the structure of the title complex salt, (Et2NH2)2[CuCl4], the asymmetric unit consists of four unique di-ethyl-ammonium cations and three unique tetra-chlorido cuprate anions. Two of the three anions are located with their copper atoms on independent crystallographic twofold axes, while the remaining tetra-chlorido cuprate is located at a general position of the ortho-rhom-bic space group P21212. Two of the three Cu atoms adopt a distorted square-planar/disphenoidal geometry and the third Cu atom has a regular square-planar coordination environment. The di-ethyl-ammonium cations form an extensive hydrogen-bonded network through N-H?Cl inter-actions with the tetra-chlorido-cuprate anions, resulting in a two-dimensional sheet-like hydrogen-bonded network parallel to the ab direction. The complex was observed to undergo a color shift from deep green at room temperature to pale yellow at temperatures above 328 K. PMID- 26870582 TI - Investigations into the construction of the penta-substituted ring C of Neosurugatoxin - a crystallographic study. AB - The crystal structures of three cyclo-penta-[c]furans with various substituents at the 4-, 5- and 6-positions of the ring system are reported, namely, (+/-) (3aR,4S,5S,6aS)-4-methyl-5-phenyl-hexa-hydro-1H-cyclo-penta-[c]furan-4,5-diol, C14H18O3, (I), (+/-)-(3aR,4S,5S,6aS)-4-benz-yloxy-4-methyl-5-phenyl-hexa-hydro-1H cyclo-penta-[c]furan-5-ol, C21H24O3, (II), and (+/-)-(1aR,1bS,4aR,5S,5aR)-5-benz yloxy-5-methyl-5a-phenyl-hexa-hydro-2H-oxireno[2',3':3,4]cyclopenta-[1,2-c]furan, C21H22O3, (III). The dominant inter-action in (I) and (II) is an O-H?O hydrogen bond across the bicyclic 5,5-ring system between the non-functionalized hy-droxy group and the tetra-hydro-furan O atom, which appears to influence the envelope conformations of the fused five-membered rings, whereas in (III), the rings have different conformations. A weak intra-molecular C-H?O inter-action appears to influence the degree of tilt of the phenyl ring attached to the 5-position and is different in (I) compared to (II) and (III). PMID- 26870583 TI - Crystal structure of tris-(trans-1,2-di-amino-cyclo-hexane-kappa(2) N,N')cobalt(III) trichloride monohydrate. AB - The synthesis of the title hydrated complex salt, [Co(C6H14N2)3]Cl3.H2O, from racemic trans-1,2-di-amino-cyclo-hexane and [CoCl(NH3)5]Cl2 and its structural characterization are presented in this paper. The product was synthesized in the inter-est of understanding the hydrogen-bonding patterns of coordination complexes. Previous characterizations of the product in the I-42d space group have not yielded coordinates; thus, this paper provides the first coordinates for this complex in this space group. The octahedrally coordinated cation adopts twofold rotation symmetry, with outer-sphere chloride counter-ions and solvent water mol-ecules forming a hydrogen-bonded network with amine H atoms. PMID- 26870584 TI - Crystal structure of the co-crystal butyl-paraben-isonicotinamide (1/1). AB - The title 1:1 co-crystal, C11H14O3.C6H6N2O [systematic name: butyl 4-hy-droxy benzoate-isonicotinamide (1/1)], crystallizes with one mol-ecule of butyl-paraben (BPN) and one mol-ecule of isonicotinamide (ISN) in the asymmetric unit. In the crystal, BPN and ISN mol-ecules form hydrogen-bonded (O-H?N and N-H?O) dimers of paired BPN and ISN mol-ecules. These dimers are further connected to each other via N-H?O=C hydrogen bonds, creating ribbons in [011] which further stack along the a axis to form a layered structure with short C?C contacts of 3.285 (3) A. Packing inter-actions within the crystal structure were assessed using PIXEL calculations. PMID- 26870585 TI - Crystal structure of a new hybrid compound based on an iodido-plumbate(II) anionic motif. AB - Crystals of the one-dimensional organic-inorganic lead iodide-based compound catena-poly[bis-(piperazine-1,4-diium) [[tetra-iodido-plumbate(II)]-MU-iodido] iodide monohydrate], (C4N2H12)2[PbI5]I.H2O, were obtained by slow evaporation at room temperature of a solution containing lead iodide and piperazine in a 1:2 molar ratio. Inorganic lead iodide chains, organic (C4N2H12)(2+) cations, water mol-ecules of crystallization and isolated I(-) anions are connected through N H?.I, N-H?OW and OW-H?I hydrogen-bond inter-actions. Zigzag chains of corner sharing [PbI6](4-) octa-hedra with composition [PbI4/1I2/2](3-) running parallel to the a axis are present in the structure packing. PMID- 26870586 TI - Crystal structure of N-{4-[(6-chloro-pyridin-3-yl)meth-oxy]phen-yl}-2,6-di-fluoro benzamide. AB - In the title compound, C19H13ClF2N2O2, the conformation of the N-H bond in the amide segment is anti to the C=O bond. The mol-ecule is not planar, with dihedral angles between the central benzene ring and the outer benzene and pyridyl rings of 73.35 (7) and 81.26 (6) degrees , respectively. A weak intra-molecular C-H?O hydrogen bond occurs. In the crystal, N-H?N, C-H?O and C-H?F hydrogen bonds lead to the formation of dimers. The N-H?N inversion dimers are linked by pi-pi contacts between adjacent pyridine rings [centroid-centroid = 3.8541 (12) A] and C-H?pi inter-actions. These contacts combine to stack the mol-ecules along the a axis. PMID- 26870587 TI - Crystal structure of K0.75[Fe(II) 3.75Fe(III) 1.25(HPO3)6].0.5H2O, an open framework iron phosphite with mixed-valent Fe(II)/Fe(III) ions. AB - Single crystals of the title compound, potassium hexa-phosphito-penta ferrate(II,III) hemihydrate, K0.75[Fe(II) 3.75Fe(III) 1.25(HPO3)6].0.5H2O, were grown under mild hydro-thermal conditions. The crystal structure is isotypic with Li1.43[Fe(II) 4.43Fe(III) 0.57(HPO3)6].1.5H2O and (NH4)2[Fe(II) 5(HPO3)6] and exhibits a [Fe(II) 3.75Fe(III) 1.25(HPO3)6](0.75-) open framework with disordered K(+) (occupancy 3/4) as counter-cations. The anionic framework is based on (001) sheets of two [FeO6] octa-hedra (one with point group symmetry 3.. and one with point group symmetry .2.) linked along [001] through [HPO3](2-) oxoanions. Each sheet is constructed from 12-membered rings of edge-sharing [FeO6] octa-hedra, giving rise to channels with a radius of ca 3.1 A where the K(+) cations and likewise disordered water mol-ecules (occupancy 1/4) are located. O?O contacts between the water mol-ecule and framework O atoms of 2.864 (5) A indicate hydrogen-bonding inter-actions of medium strength. The infrared spectrum of the compound shows vibrational bands typical for phosphite and water groups. The Mossbauer spectrum is in accordance with the presence of Fe(II) and Fe(III) ions. PMID- 26870588 TI - Crystal structure of di-chlorido-bis-(dimethyl N-cyano-dithio-imino carbonate)cobalt(II). AB - The structure of the mononuclear title complex, [{(H3CS)2C=NC N}2CoCl2], consists of a Co(II) atom coordinated in a distorted tetra-hedral manner by two Cl(-) ligands and the terminal N atoms of two dimethyl N-cyano-dithio-imino carbonate ligands. The two organic ligands are almost coplanar, with a dihedral angle of 5.99 (6) degrees between their least-squares planes. The crystal packing features pairs of inversion-related complexes that are held together through C-H?Cl and C-H?S inter-actions and pi-pi stacking [centroid-to-centroid distance = 3.515 (su?) A]. Additional C-H?Cl and C-H?S inter-actions, as well as Cl?S contacts < 3.6 A, consolidate the crystal packing. PMID- 26870589 TI - Crystal structure of (RS)-(4-chloro-phen-yl)(pyridin-2-yl)methanol. AB - In the title racemic compound, C12H10ClNO, the dihedral angle between the benzene and pyridine rings is 74.34 (6) degrees . In the crystal, the mol-ecules are linked by O-H?N hydrogen bonds, forming zigzag C(5) [001] chains in which alternating R- and S-configuration mol-ecules are related by c-glide symmetry. In addition, inversion-related pairs of mol-ecules are linked into dimers by pairs of weak C-Cl?pi(pyrid-yl) inter-actions, which link the hydrogen-bonded chains into (100) sheets. Structural comparisons are drawn with a number of related compounds. PMID- 26870590 TI - Crystal structure of tris-(di-methyl-amido-kappaN)-bis-(di-methyl-amine-kappaN) zirconium(IV) iodide. AB - Zirconium amides have become increasingly popular and useful due to their widespread use as precursors to other zirconium complexes and their use in the production of solid oxide fuel cells (SOFCs). Herein we report the mol-ecular structure of tris-(di-methyl-amido)-bis-(di-methyl-amine)-zirconium(IV) iodide, [Zr(C2H6N)3(C2H7N)2]I. The bond lengths and bond angles are consistent with a slightly distorted trigonal-bipyramidal coordination geometry around the metal atom. N?I contacts of 3.6153 (15) and 3.5922 (14) A are consistent with the presence of N-H?I inter-actions. These N-H?I inter-actions link the complex cations and iodide anions into extended chains that propagate parallel to the a axis. PMID- 26870591 TI - A 2:1 co-crystal of p-nitro-benzoic acid and N,N'-bis-(pyridin-3-ylmeth yl)ethanedi-amide: crystal structure and Hirshfeld surface analysis. AB - The title 2:1 co-crystal, 2C7H5NO4.C14H14N4O2, in which the complete di-amide mol ecule is generated by crystallographic inversion symmetry, features a three-mol ecule aggregate sustained by hydroxyl-O-H?N(pyrid-yl) hydrogen bonds. The p-nitro benzoic acid mol-ecule is non-planar, exhibiting twists of both the carb-oxy-lic acid and nitro groups, which form dihedral angles of 10.16 (9) and 4.24 (4) degrees , respectively, with the benzene ring. The di-amide mol-ecule has a conformation approximating to a Z shape, with the pyridyl rings lying to either side of the central, almost planar di-amide residue (r.m.s. deviation of the eight atoms being 0.025 A), and forming dihedral angles of 77.22 (6) degrees with it. In the crystal, three-mol-ecule aggregates are linked into a linear supra-molecular ladder sustained by amide-N-H?O(nitro) hydrogen bonds and orientated along [10-4]. The ladders are connected into a double layer via pyridyl- and benzene-C-H?O(amide) inter-actions, which, in turn, are connected into a three-dimensional architecture via pi-pi stacking inter-actions between pyridyl and benzene rings [inter-centroid distance = 3.6947 (8) A]. An evaluation of the Hirshfeld surfaces confirm the importance of inter-molecular inter-actions involving oxygen atoms as well as the pi-pi inter-actions. PMID- 26870592 TI - Crystal structure of [bis-(2-amino-ethyl-kappaN)(2-{[4-(tri-fluoro-meth-yl)benzyl idene]amino}-eth-yl)amine-kappaN]di-chlorido-copper(II). AB - The Cu(II) atom in the title compound, [CuCl2(C14H21F3N4)], adopts a coordination geometry that is between distorted square-based pyramidal and very Jahn-Teller elongated octa-hedral. It is coordinated by three N atoms from the bis-(2-amino eth-yl)(2-{[4-(tri-fluoro-meth-yl)benzyl-idene]amino}-eth-yl)amine and two chloride ligands. The two crystallographically unique copper complexes present in the asymmetric unit exhibit noticeable differences in the coordination bond lengths. Considering the Cu(II) atoms as having square-pyramidal geometry, the basal Cu-Cl bond lengths are typical [2.2701 (12) and 2.2777 (12) A], while the apical distances are considerably elongated [2.8505 (12) and 2.9415 (12) A]. For each mol-ecule, a Cu(II) atom from inversion-related mol-ecules are in nearby proximity to the remaining axial Cu(II) sites, but the Cu?Cl distances are very long [3.4056 (12) and 3.1645 (12) A], attributable to van der Waals contacts. Nonetheless, these contacts appear to have some structure-directing properties, leading to association into dimers. These dimers associate via stacking of the aromatic rings to form extended zigzag chains. PMID- 26870593 TI - Crystal structure of a mixed-ligand terbium(III) coordination polymer containing oxalate and formate ligands, having a three-dimensional fcu topology. AB - The title compound, poly[(MU 3-formato)(MU 4-oxalato)terbium(III)], [Tb(CHO2)(C2O4)] n , is a three-dimensional coordination polymer, and is isotypic with the La(III), Ce(III) and Sm(III) analogues. The asymmetric unit contains one Tb(III) ion, one formate anion (CHO2 (-)) and half of an oxalate anion (C2O4 (2 )), the latter being completed by application of inversion symmetry. The Tb(III) ion is nine-coordinated in a distorted tricapped trigonal-prismatic manner by two chelating carboxyl-ate groups from two C2O4 (2-) ligands, two carboxyl-ate oxygen atoms from another two C2O4 (2-) ligands and three oxygen atoms from three CHO2 ( ) ligands, with the Tb-O bond lengths and the O-Tb-O bond angles ranging from 2.4165 (19) to 2.478 (3) A and 64.53 (6) to 144.49 (4) degrees , respectively. The CHO2 (-) and C2O4 (2-) anions adopt MU 3-bridging and MU 4-chelating-bridging coordination modes, respectively, linking adjacent Tb(III) ions into a three dimensional 12-connected fcu topology with point symbol (3(24).4(36).5(6)). The title compound exhibits thermal stability up to 623 K, and also displays strong green photoluminescence in the solid state at room temperature. PMID- 26870594 TI - Crystal structure of 3-ferrocenyl-1-phenyl-1H-pyrrole, [Fe(eta(5)-C5H4 (c) C4H3 NPh)(eta(5)-C5H5)]. AB - The mol-ecular structure of the title compound, [Fe(C5H5)(C15H12N)], consists of a ferrocene moiety with an N-phenyl-pyrrole heterocycle bound to one cyclo-penta dienyl ring. The 1,3-disubstitution of the pyrrole results in an L-shaped arrangement of the mol-ecule with plane inter-sections of 2.78 (17) degrees between the pyrrole and the N-bonded phenyl ring and of 8.17 (18) degrees between the pyrrole and the cyclo-penta-dienyl ring. In the crystal, no remarkable inter-molecular inter-actions are observed. PMID- 26870595 TI - Crystal structures of [Mn(bdc)(Hspar)2(H2O)0.25].2H2O containing MnO6+1 capped trigonal prisms and [Cu(Hspar)2](bdc).2H2O containing CuO4 squares (Hspar = sparfloxacin and bdc = benzene-1,4-di-carboxyl-ate). AB - The syntheses and crystal structures of 0.25-aqua-(benzene-1,4-di-carboxyl-ato kappa(2) O,O')bis-(sparfloxacin-kappa(2) O,O')manganese(II) dihydrate, [Mn(C8H4O4)(C19H22F2N4O3)2(H2O)0.25].2H2O or [Mn(bdc)(Hspar)2(H2O)0.25].2H2O, (I), and bis-(sparfloxacin-kappa(2) O,O')copper(II) benzene-1,4-di-carboxyl-ate dihydrate, [Cu(C19H22F2N4O3)2](C8H4O4).2H2O or [Cu(Hspar)2](bdc).2H2O, (II), are reported (Hspar = sparfloxacin and bdc = benzene-1,4-di-carboxyl-ate). The Mn(2+) ion in (I) is coordinated by two O,O'-bidentate Hspar neutral mol-ecules (which exist as zwitterions) and an O,O'-bidentate bdc dianion to generate a distorted MnO6 trigonal prism. A very long bond [2.580 (12) A] from the Mn(2+) ion to a 0.25-occupied water mol-ecule projects through a square face of the prism. In (II), the Cu(2+) ion lies on a crystallographic inversion centre and a CuO4 square-planar geometry arises from its coordination by two O,O'-bidentate Hspar mol-ecules. The bdc dianion acts as a counter-ion to the cationic complex and does not bond to the metal ion. The Hspar ligands in both (I) and (II) feature intra-molecular N-H?O hydrogen bonds, which close S(6) rings. In the crystals of both (I) and (II), the components are linked by N-H?O, O-H?O and C-H?O hydrogen bonds, generating three-dimensional networks. PMID- 26870596 TI - Crystal structure of bis-(benzyl-amine-kappaN)[5,10,15,20-tetra-kis-(4-chloro phen-yl)porphyrinato-kappa(4) N]iron(II) n-hexane monosolvate. AB - In the title compound, [Fe(II)(C44H24Cl4N4)(C6H5CH2NH2)2].C6H14 or [Fe(II)(TPP Cl)(BzNH2)2].n-hexane [where TPP-Cl and BzNH2 are 5,10,15,20-tetra-kis-(4-chloro phen-yl)porphyrinate and benzyl-amine ligands, respectively], the Fe(II) cation lies on an inversion centre and is octa-hedrally coordinated by the four pyrrole N atoms of the porphyrin ligand in the equatorial plane and by two amine N atoms of the benzyl-amine ligand in the axial sites. The crystal structure also contains one inversion-symmetric n-hexane solvent mol-ecule per complex mol ecule. The average Fe-Npyrrole bond length [1.994 (3) A] indicates a low-spin complex. The crystal packing is sustained by N-H?Cl and C-H?Cl hydrogen-bonding inter-actions and by C-H?pi inter-molecular inter-actions, leading to a three dimensional network structure. PMID- 26870597 TI - Crystal structure of 7,8,9,10-tetra-hydro-benzo[b]naphtho-[2,1-d]furan. AB - In the title compound, C16H14O, the cyclo-hexene ring has a half-chair conformation. The mean plane, calculated through all non-H atoms of the mol ecule, except for the central CH2 atoms of the cyclo-hexene ring, which deviate by 0.340 (3) and -0.369 (3) A from this mean plane, has an r.m.s. deviation of 0.012 A. In the crystal, there are C-H?pi contacts present, resulting in the formation of zigzag chains propagating along the [010] direction. PMID- 26870598 TI - The continuing transformation of Acta Crystallographica Section E and the launch of IUCrData. PMID- 26870599 TI - Face Basosquamous Carcinoma, a Case Report. AB - Face basosquamous or metatypical carcinoma is a rare and controversial form of skin cancer. It is characterized by increased incidence of recurrence and distant metastases. We present the case of a patient of 71 years with an ulcerative lesion of 3/4 cm in the nasal pyramid. The injury occurred due to trauma to the nasal pyramid, produced 13 years ago. After investigation, which included ORL examination, imaging and oncology exam, surgery was decided to completely ablate tumor formation. The resulted defect of 4/5 cm was covered by mobilizing a forehead flap based on right supratrohleare artery pedicle. Histopathological examination revealed the diagnosis of basosquamous or metatypical carcinoma. The patient was referred to the oncology service for treatment. PMID- 26870600 TI - Surgical Repair of Abdominal Aortic and Renal Artery Aneurysms in Takayasu's Arteritis. AB - Takayasu's arteritis is a large vessel vasculitis that can be a challenging diagnosis to make and has a varied clinical presentation. Management largely depends on affected vessel disease severity and individual patient considerations. The diagnosis must be considered in a young patient with large vessel aneurysms. We present a case of a 30 year-old woman of Pacific Islander descent who presented to the Tripler Army medical Center Vascular Surgery Department in Honolulu, Hawai'i seeking repair of her abdominal aortic and renal artery aneurysms prior to conception. A 30 year-old Pacific Islander woman with a history of a saccular abdominal aortic aneurysm and renal artery aneurysms presented to our clinic seeking vascular surgery consultation prior to a planned pregnancy. She had a renal artery stent placed at an outside institution for hypertension. She met the diagnosis of Takayasu's arteritis by Sharma's criteria. Physical exam was significant for a palpable, pulsatile, abdominal mass and CT angiography revealed a saccular irregular-appearing infra-renal abdominal aortic aneurysm, extending to the aortic bifurcation, with a maximum diameter of 3.3 cm. A right renal artery aneurysm was also identified proximally, contiguous with the aorta, with a maximal transverse diameter of 1.7 cm. The patient underwent a supraceliac bypass to the right renal artery with a 7 mm Dacron graft, as well as excision of the right renal artery aneurysm. The abdominal aortic aneurysm was replaced using a Hemashield Dacron bifurcated 14 mm x 7 mm bypass graft. Intraoperative measurements of the renal artery aneurysm were 1.5 x 1.5 cm and the saccular appearing distal abdominal aortic aneurysm measured 3.6 x 3.3 cm. The patient was discharged from the hospital 7 days post-operatively. At 1-year follow up, CT scan of the abdominal aorta revealed the repair was without any evidence of aneurysm formation, anastomotic pseudoaneurysm formation, or areas of stenosis. She has remained normotensive with a normal serum creatinine 18 months after her repair. She has since delivered her second child. It is rare for Takayasu's arteritis to present with aneurysmal disease. It is much more common to present with stenosis or occlusion. It has yet to be proven that Takayasu's truly has a higher incidence in those of Asian descent. Takayasu's can be a difficult diagnosis to make but can be aided with the use of Sharma's criteria. Our particular patient posed unique considerations on the effects of the physiology of pregnancy on her aneurysms and repair. Managing the active phases of disease is imperative, and though medical management is first line, surgical intervention may be necessary. Surgical intervention should be performed in a quiescent period of disease if possible given that biological inflammation at the time of intervention increases the complication rate. Repair of aneurysmal disease in a young female should also be considered prior to pregnancy. PMID- 26870601 TI - The Paradox of Discrimination, the "Aloha Spirit," and Symptoms of Depression in Hawai'i. AB - It remains to be determined whether the "aloha spirit" is a cultural resource that influences psychological well-being in Hawai'i. Thus, the purpose of this study is to investigate whether the aloha spirit is associated with levels of psychological distress and the risk of depression, while taking into account various risk factors. Data for this study were drawn from an anonymous survey of undergraduate students (N = 1,028) at the University of Hawai'i. Regression results revealed that having learned the aloha spirit was associated with significantly lower levels (b = -1.76; P < .01) of psychological distress and a reduced odds of depression (OR = .69; P < .01) over and above the effects of perceived discrimination, local identity, levels of ethnic identification, race/ethnicity, immigrant status, duration of residence in Hawai'i, and other sociodemographic factors. In contrast, everyday discrimination was associated with significantly higher levels (b = 0.41; P < .001) of psychological distress and a greater odds of depression (OR = 1.08; P < .001). Together, these findings highlight the paradox of discrimination and the aloha spirit in Hawai'i by documenting their distinct relationships with mental health. Overall, this study contributes to medical and public health research on mental health disparities during the transition to adulthood by delving into the social context of daily life in the understudied, multicultural location of Hawai'i. PMID- 26870603 TI - Medical School Hotline: Cultural Competency in Serving the Homeless in Hawai'i at the John A. Burns School of Medicine. PMID- 26870602 TI - Colonoscopy Screening among Native Hawaiians at Queen's Medical Center between August 2011 and January 2013. AB - A retrospective chart review in the Endoscopy Department at Queen's Medical Center identified 358 Native Hawaiian patients who had completed a colonoscopy screening procedure between August 2011 and January 2013, through either the Direct Referral Colonoscopy program or its Traditional Referral program. The differences in the characteristics of Native Hawaiian patients were summarized and compared between the two referral programs to identify potential barriers for future interventions and increase colorectal cancer screening. The combined colonoscopy screening rate among Native Hawaiians was 13%. Younger patients and those with private insurance were found to be undergoing colonoscopy screening through the Direct Referral program. The findings of this study underscore the need to reduce disparities in colonoscopy screening among Native Hawaiians. PMID- 26870604 TI - Insights in Public Health: Building Well-Being: Linking the Built Environment to Health. PMID- 26870605 TI - The Daniel K. Inouye College of Pharmacy Scripts: Prescription Drug Pricing. AB - Prescription drugs have reduced morbidity and mortality and improved the quality of life of millions of Americans. Yet, concerns over drug price increases loom. Drug spending has risen relatively slowly over the past decade because many of the most popular brand-name medicines lost patent protection. In the near future, there will be fewer low-cost generics coming into the market to offset the rising prices of brand-name drugs. Drug expenditures are influenced by both volume and price. This article focuses on how drug prices are set in the United States and current trends. Drug prices are determined through an extremely complicated set of interactions between pharmaceutical manufacturers, wholesalers, retailers, insurers, pharmacy benefit managers (PBMs), managed care organizations, hospitals, chain stores, and consumers. The process differs depending on the type of drug and place of delivery. Rising drug prices have come under increased scrutiny due to increased cost inflation and because many price increases come as a result of mergers and acquisitions of generic drug companies or changes in ownership of brand name drug manufacturers. Other countries have reigned in drug prices by negotiating with or regulating pharmaceutical manufacturers. The best long-term solution to rising drug prices is yet to be determined but the United States will continue to debate this issue and the discussions will get more heated if drug expenditures continue to rise at a rapid rate (ie, increasing 13% in 2014 from the previous year). PMID- 26870607 TI - Can we set a global threshold age to define mature forests? AB - Globally, mature forests appear to be increasing in biomass density (BD). There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1) how climate and forest age control global forest BD and (2) whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost effectiveness of different methods for determining whether forests should be classified as mature. PMID- 26870608 TI - A comparison of rumen microbial profiles in dairy cows as retrieved by 454 Roche and Ion Torrent (PGM) sequencing platforms. AB - Next generation sequencing (NGS) technology is a widely accepted tool used by microbial ecologists to explore complex microbial communities in different ecosystems. As new NGS platforms continue to become available, it becomes imperative to compare data obtained from different platforms and analyze their effect on microbial community structure. In the present study, we compared sequencing data from both the 454 and Ion Torrent (PGM) platforms on the same DNA samples obtained from the rumen of dairy cows during their transition period. Despite the substantial difference in the number of reads, error rate and length of reads among both platforms, we identified similar community composition between the two data sets. Procrustes analysis revealed similar correlations (M (2) = 0.319; P = 0.001) in the microbial community composition between the two platforms. Both platforms revealed the abundance of the same bacterial phyla which were Bacteroidetes and Firmicutes; however, PGM recovered an additional four phyla. Comparisons made at the genus level by each platforms revealed differences in only a few genera such as Prevotella, Ruminococcus, Succiniclasticum and Treponema (p < 0.05; chi square test). Collectively, we conclude that the output generated from PGM and 454 yielded concurrent results, provided stringent bioinformatics pipelines are employed. PMID- 26870609 TI - PhyloPythiaS+: a self-training method for the rapid reconstruction of low-ranking taxonomic bins from metagenomes. AB - Background. Metagenomics is an approach for characterizing environmental microbial communities in situ, it allows their functional and taxonomic characterization and to recover sequences from uncultured taxa. This is often achieved by a combination of sequence assembly and binning, where sequences are grouped into 'bins' representing taxa of the underlying microbial community. Assignment to low-ranking taxonomic bins is an important challenge for binning methods as is scalability to Gb-sized datasets generated with deep sequencing techniques. One of the best available methods for species bins recovery from deep branching phyla is the expert-trained PhyloPythiaS package, where a human expert decides on the taxa to incorporate in the model and identifies 'training' sequences based on marker genes directly from the sample. Due to the manual effort involved, this approach does not scale to multiple metagenome samples and requires substantial expertise, which researchers who are new to the area do not have. Results. We have developed PhyloPythiaS+, a successor to our PhyloPythia(S) software. The new (+) component performs the work previously done by the human expert. PhyloPythiaS+ also includes a new k-mer counting algorithm, which accelerated the simultaneous counting of 4-6-mers used for taxonomic binning 100 fold and reduced the overall execution time of the software by a factor of three. Our software allows to analyze Gb-sized metagenomes with inexpensive hardware, and to recover species or genera-level bins with low error rates in a fully automated fashion. PhyloPythiaS+ was compared to MEGAN, taxator-tk, Kraken and the generic PhyloPythiaS model. The results showed that PhyloPythiaS+ performs especially well for samples originating from novel environments in comparison to the other methods. Availability. PhyloPythiaS+ in a virtual machine is available for installation under Windows, Unix systems or OS X on: https://github.com/algbioi/ppsp/wiki. PMID- 26870610 TI - miR-27b attenuates apoptosis induced by transmissible gastroenteritis virus (TGEV) infection via targeting runt-related transcription factor 1 (RUNX1). AB - Transmissible gastroenteritis virus (TGEV), belonging to the coronaviridae family, is the key cause of the fatal diarrhea of piglets and results in many pathological processes. microRNAs (miRNAs) play a key role in the regulation of virus-induced apoptosis. During the process of apoptosis induced by TGEV infection in PK-15 cells, the miR-27b is notably down-regulated. Thus, we speculate that miR-27b is involved in regulating the process of apoptosis in PK 15 cells. In this study we demonstrated that the over-expression of miR-27b led to the inhibition of TGEV-induced apoptosis, reduction of Bax protein level, and decrease of caspase-3 and -9 activities. Conversely, silencing of miR-27b by miR 27b inhibitors enhanced apoptosis via up-regulating Bax expression and promoting the activities of caspase-3 and -9 in TGEV-infected cells. Subsequently, the runt related transcription factor 1 (RUNX1) is a candidate target of miR-27b predicted by bioinformatics search. We further identified that the miR-27b directly bound to the 3' UTR of RUNX1 mRNA and suppressed RUNX1 expression, which indicates RUNX1 is the direct target gene of miR-27b. The over-expression of RUNX1 increased apoptosis and knockdown RUNX1blocked apoptosis of viral-infected cells via regulating Bax expression and the activities of caspase-3 and -9. Our data reveal that miR-27b may repress the mitochondrial pathway of apoptosis by targeting RUNX1, indicating that TGEV may induce apoptosis via down-regulating miR-27b and that miR-27b may act as a target for therapeutic intervention. PMID- 26870611 TI - Inside-out flowers of Lacandonia brasiliana (Triuridaceae) provide new insights into fundamental aspects of floral patterning. AB - Background and Aims. A recently described Brazilian species, Lacandonia brasiliana, shares with its longer established putative sister species from Mexico, L. schismatica, inverted floral patterning (carpels surrounding stamens) that is almost unique among angiosperms. We present a detailed ontogenetic study of L. brasiliana for comparison with other members of the tribe Triurideae (Triuridaceae) to explore the possible evolutionary origins of "inside-out" flowers. Methods. Wild-source populations of L. brasiliana were compared morphologically and ontogenetically with related species of Triurideae, using light and scanning electron microscopy. Key Results. Relatively few morphological differences separate flowers of L. brasiliana and L. schismatica. Both species have tepals with late-developing subapical appendages. In both species, the three central (almost sessile) anthers develop precociously with respect to the carpels; the anthers remain closed, and fertilization is achieved via pollen-tube growth from germinating pollen grains of the same cleistogamous flower. Carpels are initiated on fascicles. Conclusions. The close similarity between the two Lacandonia species makes it unlikely that they arose independently from two separate homeotic transformation events; they could either represent sister species or two populations of a single disjunct species. Our study underlines the problematic generic and species boundaries within Triurideae. We present an evolutionary scenario of character evolution in Triuridaceae. The inside-out Lacandonia flower could have resulted from a stabilized homeotic transformation; this hypothesis is not in conflict with constrasting theories of the origin of the Triuridaceae flower, which coincided with a shift to unisexuality. The unisexual yet highly plastic flowers that are typical of Triuridaceae could have pre-adapted the origin of the extraordinary Lacandonia morphology. PMID- 26870612 TI - Gene expression changes in diapause or quiescent potato cyst nematode, Globodera pallida, eggs after hydration or exposure to tomato root diffusate. AB - Plant-parasitic nematodes (PPN) need to be adapted to survive in the absence of a suitable host or in hostile environmental conditions. Various forms of developmental arrest including hatching inhibition and dauer stages are used by PPN in order to survive these conditions and spread to other areas. Potato cyst nematodes (PCN) (Globodera pallida and G. rostochiensis) are frequently in an anhydrobiotic state, with unhatched nematode persisting for extended periods of time inside the cyst in the absence of the host. This paper shows fundamental changes in the response of quiescent and diapaused eggs of G. pallida to hydration and following exposure to tomato root diffusate (RD) using microarray gene expression analysis encompassing a broad set of genes. For the quiescent eggs, 547 genes showed differential expression following hydration vs. hydratation and RD (H-RD) treatment whereas 708 genes showed differential regulation for the diapaused eggs following these treatments. The comparison between hydrated quiescent and diapaused eggs showed marked differences, with 2,380 genes that were differentially regulated compared with 987 genes following H-RD. Hydrated quiescent and diapaused eggs were markedly different indicating differences in adaptation for long-term survival. Transport activity is highly up regulated following H-RD and few genes were coincident between both kinds of eggs. With the quiescent eggs, the majority of genes were related to ion transport (mainly sodium), while the diapaused eggs showed a major diversity of transporters (amino acid transport, ion transport, acetylcholine or other molecules). PMID- 26870613 TI - Molecular characterisation of the Chlamydia pecorum plasmid from porcine, ovine, bovine, and koala strains indicates plasmid-strain co-evolution. AB - Background. Highly stable, evolutionarily conserved, small, non-integrative plasmids are commonly found in members of the Chlamydiaceae and, in some species, these plasmids have been strongly linked to virulence. To date, evidence for such a plasmid in Chlamydia pecorum has been ambiguous. In a recent comparative genomic study of porcine, ovine, bovine, and koala C. pecorum isolates, we identified plasmids (pCpec) in a pig and three koala strains, respectively. Screening of further porcine, ovine, bovine, and koala C. pecorum isolates for pCpec showed that pCpec is common, but not ubiquitous in C. pecorum from all of the infected hosts. Methods. We used a combination of (i) bioinformatic mining of previously sequenced C. pecorum genome data sets and (ii) pCpec PCR-amplicon sequencing to characterise a further 17 novel pCpecs in C. pecorum isolates obtained from livestock, including pigs, sheep, and cattle, as well as those from koala. Results and Discussion. This analysis revealed that pCpec is conserved with all eight coding domain sequences (CDSs) present in isolates from each of the hosts studied. Sequence alignments revealed that the 21 pCpecs show 99% nucleotide sequence identity, with 83 single nucleotide polymorphisms (SNPs) shown to differentiate all of the plasmids analysed in this study. SNPs were found to be mostly synonymous and were distributed evenly across all eight pCpec CDSs as well as in the intergenic regions. Although conserved, analyses of the 21 pCpec sequences resolved plasmids into 12 distinct genotypes, with five shared between pCpecs from different isolates, and the remaining seven genotypes being unique to a single pCpec. Phylogenetic analysis revealed congruency and co evolution of pCpecs with their cognate chromosome, further supporting polyphyletic origin of the koala C. pecorum. This study provides further understanding of the complex epidemiology of this pathogen in livestock and koala hosts and paves the way for studies to evaluate the function of this putative C. pecorum virulence factor. PMID- 26870614 TI - A model for HIV disclosure of a parent's and/or a child's illness. AB - HIV prevalence in Kenya remains steady at 5.6% for adults 15 years and older, and 0.9% among children aged below 14 years. Parents and children are known to practice unprotected sex, which has implications for continued HIV spread within the country. Additionally, due to increased accessibility of antiretroviral therapy, more HIV-positive persons are living longer. Therefore, the need for HIV disclosure of a parent's and/or a child's HIV status within the country will continue for years to come. We conducted a qualitative phenomenological study to understand the entire process of disclosure from the time of initial HIV diagnosis of an index person within an HIV-affected family, to the time of full disclosure of a parent's and/or a child's HIV status to one or more HIV-positive, negative, or untested children within these households. Participants were purposively selected and included 16 HIV-positive parents, seven HIV-positive children, six healthcare professionals (physician, clinical officer, psychologist, registered nurse, social worker, and a peer educator), and five HIV negative children. All participants underwent an in-depth individualized semistructured interview that was digitally recorded. Interviews were transcribed and analyzed in NVivo 8 using the modified Van Kaam method. Six themes emerged from the data indicating that factors such as HIV testing, living with HIV, evolution of disclosure, questions, emotions, benefits, and consequences of disclosure interact with each other and either impede or facilitate the HIV disclosure process. Kenya currently does not have guidelines for HIV disclosure of a parent's and/or a child's HIV status. HIV disclosure is a process that may result in poor outcomes in both parents and children. Therefore, understanding how these factors affect the disclosure process is key to achieving optimal disclosure outcomes in both parents and children. To this end, we propose an HIV disclosure model incorporating these six themes that is geared at helping healthcare professionals provide routine, clinic-based, targeted, disclosure related counseling/advice and services to HIV-positive parents and their HIV positive, HIV-negative, and untested children during the HIV disclosure process. The model should help improve HIV disclosure levels within HIV-affected households. Future researchers should test the utility and viability of our HIV disclosure model in different settings and cultures. PMID- 26870615 TI - LPS- or Pseudomonas aeruginosa-mediated activation of the macrophage TLR4 signaling cascade depends on membrane lipid composition. AB - It is well known that PUFA impede the LPS-mediated activation of the transcription factor NFkappaB. However, the underlying mode of action has not been clarified yet. To address this issue in a comprehensive approach, we used the monocyte/macrophage cell line RAW264.7 to investigate the consequences of a PUFA supplementation on the TLR4 pathway with a focus on (i) the gene expression of TLR4 itself as well as of its downstream mediators, (ii) the membrane microdomain localization of TLR4 and CD14, (iii) the stimulation-induced interaction of TLR4 and CD14. Our data indicate that the impairment of the TLR4 mediated cell activation by PUFA supplementation is not due to changes in gene expression of mediator proteins of the signaling cascade. Rather, our data provide evidence that the PUFA enrichment of macrophages affects the TLR4 pathway at the membrane level. PUFA incorporation into membrane lipids induces a reordering of membrane microdomains thereby affecting cellular signal transduction. It is important to note that this remodeling of macrophage rafts has no adverse effect on cell viability. Hence, microdomain disruption via macrophage PUFA supplementation has a potential as non-toxic strategy to attenuate inflammatory signaling. PMID- 26870616 TI - Role of heparan sulfate in mediating CXCL8-induced endothelial cell migration. AB - CXCL8 (Interleukin-8, IL-8) plays an important role in angiogenesis and wound healing by prompting endothelial cell migration. It has been suggested that heparan sulfate (HS) could provide binding sites on endothelial cells to retain and activate highly diffusible cytokines and inflammatory chemokines. In the present study, we aimed to test the hypothesis that HS is essential for enhancement of endothelial cell migration by CXCL8, and to explore the underlying mechanism by detecting the changes in expression and activity of Rho GTPases and in the organization of actin cytoskeleton after enzymatic removal of HS on human umbilical vein endothelial cells (HUVECs) by using heparinase III. Our results revealed that the wound healing induced by CXCL8 was greatly attenuated by removal of HS. The CXCL8-upregulated Rho GTPases including Cdc42, Rac1, and RhoA, and CXCL8-increased Rac1/Rho activity were suppressed by removal of HS. The polymerization and polarization of actin cytoskeleton, and the increasing of stress fibers induced by CXCL8 were also abolished by heparinase III. Taken together, our results demonstrated an essential role of HS in mediating CXCL8 induced endothelial cell migration, and highlighted the biological importance of the interaction between CXCL8 and heparan sulfate in wound healing. PMID- 26870617 TI - Identification of fibrillogenic regions in human triosephosphate isomerase. AB - Background. Amyloid secondary structure relies on the intermolecular assembly of polypeptide chains through main-chain interaction. According to this, all proteins have the potential to form amyloid structure, nevertheless, in nature only few proteins aggregate into toxic or functional amyloids. Structural characteristics differ greatly among amyloid proteins reported, so it has been difficult to link the fibrillogenic propensity with structural topology. However, there are ubiquitous topologies not represented in the amyloidome that could be considered as amyloid-resistant attributable to structural features, such is the case of TIM barrel topology. Methods. This work was aimed to study the fibrillogenic propensity of human triosephosphate isomerase (HsTPI) as a model of TIM barrels. In order to do so, aggregation of HsTPI was evaluated under native like and destabilizing conditions. Fibrillogenic regions were identified by bioinformatics approaches, protein fragmentation and peptide aggregation. Results. We identified four fibrillogenic regions in the HsTPI corresponding to the beta3, beta6, beta7 y alpha8 of the TIM barrel. From these, the beta3-strand region (residues 59-66) was highly fibrillogenic. In aggregation assays, HsTPI under native-like conditions led to amorphous assemblies while under partially denaturing conditions (urea 3.2 M) formed more structured aggregates. This slightly structured aggregates exhibited residual cross-beta structure, as demonstrated by the recognition of the WO1 antibody and ATR-FTIR analysis. Discussion. Despite the fibrillogenic regions present in HsTPI, the enzyme maintained under native-favoring conditions displayed low fibrillogenic propensity. This amyloid-resistance can be attributed to the three-dimensional arrangement of the protein, where beta-strands, susceptible to aggregation, are protected in the core of the molecule. Destabilization of the protein structure may expose inner regions promoting beta-aggregation, as well as the formation of hydrophobic disordered aggregates. Being this last pathway kinetically favored over the thermodynamically more stable fibril aggregation pathway. PMID- 26870618 TI - Durable Disease Control with MEK Inhibition in a Patient with NRAS-mutated Atypical Chronic Myeloid Leukemia. AB - Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare hematologic neoplasms characterized by leukocytosis and a hypercellular bone marrow. Although recurrent mutations in the colony-stimulating factor 3 receptor (CSF3R) are frequently observed in patients with (CNL), the mutational landscape in (aCML) is less well-defined. In this report, we describe an 81-year old male who was diagnosed with aCML. He presented with leukocytosis and anemia but no significant clinical symptoms. Standard laboratory studies revealed the absence of the Philadelphia chromosome. Massively parallel sequencing demonstrated no mutations in CSF3R, but the presence of a heterozygous NRAS-G12D variant (47% allele frequency). The patient was started on treatment with trametinib, an MEK1/2 inhibitor with Food and Drug Administration approval for malignant melanoma. Therapy with trametinib resulted in exceptional improvements in his blood counts and continued disease control with 14 months of follow-up. This case highlights the need for clinical trials evaluating the safety and efficacy of MEK1/2 as a therapeutic target for the treatment of patients with NRAS-mutated aCML/CNL. PMID- 26870620 TI - Policy Address. PMID- 26870619 TI - Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101. AB - Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types. We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.. PMID- 26870621 TI - Health Literacy Training for Public Health Nurses in Fukushima: A Multi-site Program Evaluation. AB - Public health nurses (PHNs) are community residents' access points to health information and services in Japan. After the Fukushima nuclear accident, they were challenged to communicate radiation-related health information to best meet community needs. We previously developed and evaluated the outcome of a single site health literacy training program to augment PHNs' ability to improve community residents' access to written health information. This paper presents an evaluation of an identical training program using data combined from multiple sites, and further included proximal and distal evaluations to document the impact of health literacy training in a post-disaster setting. A total of 64 participants, primarily experienced PHNs, attended one of three multi-session health literacy workshops conducted in multiple sites across Fukushima. Quantitative and qualitative data on PHNs' training satisfaction, self-evaluation of achievements regarding training goals, and application of learned skills were collected and analyzed. Each workshop consisted of two 2-hour sessions introducing health literacy and assessment tools and developing skills to improve written materials, followed by a one-month follow-up assessment on PHNs' application of the gained skills in the field. Post-training evaluations on the appropriateness and usefulness of the workshop were highly positive. At the end of the one-month follow-up, 45% of participants had gained confidence in assessing and revising written materials and had applied the skills they had gained to develop and communicate health information in various settings and modes. This increase in confidence was associated with further application of the learned skills at the municipal level. However, participants reported difficulties in explaining risks, and the need to learn more about plain language to be able to paraphrase professional terms. This paper highlighs the positive outcomes of health literacy training among PHNs. Practical strategies to reinforce their skills to use plain language and communicate the epidemiological concept of risk are also recommended. PMID- 26870623 TI - Looking Back on My 44 Years with Japan: Connecting with Medicine, Public Health, and International Health. PMID- 26870622 TI - Study of Global Health Strategy Based on International Trends: -Promoting Universal Health Coverage Globally and Ensuring the Sustainability of Japan's Universal Coverage of Health Insurance System: Problems and Proposals. AB - The Japanese government at present is implementing international health and medical growth strategies mainly from the viewpoint of business. However, the United Nations is set to resolve the Post-2015 Development Agenda in the fall of 2015; the agenda will likely include the achievement of universal health coverage (UHC) as a specific development goal. Japan's healthcare system, the foundation of which is its public, nationwide universal health insurance program, has been evaluated highly by the Lancet. The World Bank also praised it as a global model. This paper presents suggestions and problems for Japan regarding global health strategies, including in regard to several prerequisite domestic preparations that must be made. They are summarized as follows. (1) The UHC development should be promoted in coordination with the United Nations, World Bank, and Asian Development Bank. (2) The universal health insurance system of Japan can be a global model for UHC and ensuring its sustainability should be considered a national policy. (3) Trade agreements such as the Trans-Pacific Partnership (TPP) should not disrupt or interfere with UHC, the form of which is unique to each nation, including Japan. (4) Japan should disseminate information overseas, including to national governments, people, and physicians, regarding the course of events that led to the establishment of the Japan's universal health insurance system and should make efforts to develop international human resources to participate in UHC policymaking. (5) The development of separate healthcare programs and UHC preparation should be promoted by streamlining and centralizing maternity care, school health, infectious disease management such as for tuberculosis, and emergency medicine such as for traffic accidents. (6) Japan should disseminate information overseas about its primary care physicians (kakaritsuke physicians) and develop international human resources. (7) Global health should be developed in integration with global environment problem management. (8) Support systems, such as for managing large-scale disasters of international scale or preventing the spread of infectious diseases, should be developed and maintained. (9) International healthcare policy, which the Japanese government is trying to promote in accordance with international trends, and international development of Japanese healthcare industry should be reconsidered. PMID- 26870624 TI - Participation in Relief Activities in the Aftermath of the Great Nepal Earthquake and Disaster Reconstruction Assistance. PMID- 26870625 TI - Report from the Junior Doctors Network on the WMA Council Session and JDN Meeting, Oslo 2015. PMID- 26870626 TI - Managing a Narrow Escape from Death. PMID- 26870627 TI - From the Editor's Desk. PMID- 26870634 TI - For 'Physitians of the Soule': The Roles of 'Flight' and 'Hatred of Abomination' in Thomas Wright's The Passions of the Minde in Generall. AB - This article attempts to understand how Thomas Wright's 1604 work, The Passions of the Minde in Generall, might have fitted into his overall mission as an English Catholic preacher, particularly when read via Wright's understanding of Thomas Aquinas's passion of fuga seu abominatio. Some historians claim that Wright was a controversialist, previously describing The Passions as either a radical departure from Wright's mission, or the work of a different Thomas Wright. Earlier attempts to find a missionary element within The Passions have been inadequate. Through a close reading of The Passions, specifically analysing Wright's interpretation of fuga seu abominatio within the context of Wright's intended readership, the main message of The Passions, and his background, this article suggests a possible reading of the text as a work aimed specifically at fellow English Catholics. To Wright, the passions of hatred of abomination and flight or detestation, derived primarily from Aquinas's fuga seu abominatio, were not simply a form of disgust, as often assumed, but the potential worldly or otherworldly harm that someone we love, such as a neighbour, might face from the abominable evil of sin and damnation. By linking hatred of abomination, flight or detestation, and Wright's particular view of sin together, Wright was teaching English Catholics how these passions might be used to cure diseased souls, turning the work into a guide for preaching. PMID- 26870635 TI - Ly6G-mediated depletion of neutrophils is dependent on macrophages. AB - Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings. PMID- 26870636 TI - Capsular Plication for Treatment of Iatrogenic Hip Instability. AB - The most commonly reported reasons for persistent hip pain after hip arthroscopy are residual femoroacetabular impingement, dysplasia and dysplasia variants, or extra-articular impingement. There are some cases in which the underlying osseous pathomorphology has been appropriately treated, and the cause of persistent hip pain can be soft-tissue injuries such as chondrolabral tears or capsular abnormalities. Capsular defects after hip arthroscopy may suggest an alteration of the biomechanical properties of the iliofemoral ligament and lead to iatrogenically induced hip instability. There are a growing number of biomechanical and clinical studies showing the importance of capsular management during hip arthroscopy. We describe the workup, examination under anesthesia, diagnostic arthroscopy, and technique of capsular plication for iatrogenic instability of the hip. PMID- 26870637 TI - Arthroscopic Scapulothoracic Decompression for Snapping Scapula Syndrome. AB - Snapping scapula syndrome at the superomedial corner of the scapula can lead to significant shoulder dysfunction. Bursectomy with or without partial scapulectomy is currently the most beneficial primary method of treatment in patients in whom nonoperative therapy fails. Arthroscopic access to the scapulothoracic space is simple and reproducible with the technique described in this report. The bursal tissue can be cleared, optimizing visualization of the scapulothoracic space and the anatomic structures. Arthroscopic decompression of the scapulothoracic bursa and resection of the superomedial corner of the scapula are highlighted in a video example. PMID- 26870638 TI - Arthroscopic Superior Capsular Reconstruction for Treatment of Massive Irreparable Rotator Cuff Tears. AB - Massive irreparable rotator cuff tears have been troublesome entities to treat, especially in younger patients. Few good options exist, leaving most patients in recent years receiving a reverse total shoulder arthroplasty. Reverse shoulder arthroplasty carries serious risks, a limited lifespan, and no other viable options should it fail. Recent biomechanical studies have shown that the superior capsule is critical to containing the glenohumeral joint reduced, allowing the larger muscles like the deltoid and pectoralis major to function properly. The superior capsular reconstruction is an anatomic reconstruction of the superior capsule to restore the normal restraint to superior translation that occurs with a deficient rotator cuff. The technique described in this article is an arthroscopic reconstruction of the superior capsule with dermal allograft. PMID- 26870639 TI - Inside-Out Trans-Arthroscopic Drain Application During Knee Joint Arthroscopy. AB - Although knee joint arthroscopy is one of the most frequently performed surgical procedures worldwide, there is no consensus on how to apply a drain in the joint if it is decided to use one. Therefore we describe a simple technique to safely apply a drain intra-articularly under full arthroscopic control, avoiding placement of the drain through the arthroscopic portal. PMID- 26870640 TI - Arthroscopic Treatment of Annular Drive Through and Radial Lateral Collateral Ligament Articular-Side Tear of the Elbow. AB - An elongation or partial articular-sided tear of the radial lateral collateral ligament (R-LCL) is a rare injury causing disability and instability of the elbow. In our experience this condition is often associated with a pathologic sign of the annular ligament named the "annular drive through" caused by a redundancy of the ligament. The benefits of performing an arthroscopic procedure for surgical stabilization of the R-LCL include smaller incisions with less soft tissue dissection, better visualization of the joint, better repair accessibility, and elimination of the annular drive-through sign. The main steps of the operation are as follows: evaluation of annular drive through, inspection of the radial side of the joint, anterior capsulotomy, insertion of a suture anchor through the anterolateral portal, shuttling of the suture anchor through the ligament, and elimination of the annular drive-through sign. By use of this technique, it is possible to repair a lesion of the R-LCL with a suture anchor that ensures an anatomic repair and, at the same time, returns the annular ligament to its physiological tension. PMID- 26870641 TI - Endoscopic Ganglionectomy of the Elbow. AB - Resection of the ganglion of the elbow is indicated if the size or location of the cyst impairs function or causes significant pain. Arthroscopic decompression or endoscopic resection of the cyst is the minimally invasive surgical option. It has the potential advantage of better cosmetic results and less soft-tissue dissection. Endoscopic resection is indicated if the cyst is not communicating with the joint or the communication is not identifiable arthroscopically or if there is a long and narrow communication placing the cyst away from the elbow joint. Preoperative magnetic resonance imaging is essential for surgical planning. PMID- 26870642 TI - Arthroscopic-Assisted Management of Unstable Distal-Third Clavicle Fractures: Conoid Ligament Reconstruction and Fracture Cerclage With Sutures. AB - Surgical treatment is usually indicated for the management of Neer type IIB fractures of the distal third of the clavicle. These unstable injuries have shown a rate of nonunion that oscillates around 30% to 45% when managed conservatively, and surgical strategies often require a second operation for implant removal. We describe an arthroscopic-assisted technique for the treatment of Neer type IIB unstable distal-third clavicle fractures that overcomes the issues related to open surgery, metal hardware, and implant irritation. This technique increases the load to failure of the construct by means of adding a synthetic conoid ligament reconstruction with a nonrigid suspension device, and it allows the diagnosis and treatment of associated glenohumeral injuries. Our technique incorporates a fracture interfragmentary fixation with sutures, thus avoiding a second operation for implant removal. PMID- 26870643 TI - Treatment of Osteochondral Lesions of the Talus With Bone Marrow Stimulation and Chitosan-Glycerol Phosphate/Blood Implants (BST-CarGel). AB - Bone marrow stimulation (BMS) techniques represent the first-line treatment for unstable osteochondral lesions of the talus or after conservative treatment failure. These techniques are intended to penetrate the subchondral bone to elicit bleeding and allow precursor cells and cytokines from bone marrow to populate the lesion. However, the fibrocartilaginous repair tissue arising after marrow stimulation confers inferior mechanical and biological properties compared with the original hyaline cartilage. The limitations of BMS can be overcome by the use of the soluble chitosan-based polymer BST-CarGel (Piramal Life Sciences, Laval, Quebec, Canada). When mixed with freshly drawn autologous whole blood and applied to a lesion surgically prepared by BMS, BST-CarGel acts as a natural bioscaffold that increases the quantity and improves the residency of the blood clot formed in the cartilage lesion, enhancing the local healing response. The use of BST-CarGel has been previously described in the knee and hip joints with successful results. We describe the arthroscopic technique for BST-CarGel application in combination with BMS techniques for the treatment of osteochondral lesions of the talus. PMID- 26870644 TI - Arthroscopic Repair of a Posterior Bony Bankart Lesion. AB - Posterior bony defects of the glenoid rim, particularly those associated with instability, are often a frustrating challenge for arthroscopists because of the defects' inaccessibility from standard portals. This challenge is enhanced when the lesion is chronic and fibrous malunion of the fragment makes mobilization difficult. We present our technique for arthroscopic repair of the relatively uncommon chronic posterior bony Bankart lesion. By use of lateral positioning and a standard anterior viewing portal and posterior working portal, as well as a strategically placed posterolateral accessory portal, the lesion is first freed from its malreduced position and ultimately repaired using suture anchor fixation of the bony fragment along with its associated labrum directly to the remaining glenoid rim. This technique, facilitated by precise portal placement, results in satisfactory fragment reduction, appropriate capsular tension, and restoration of anatomy. PMID- 26870645 TI - Hip Arthroscopic Osteochondral Autologous Transplantation for Treating Osteochondritis Dissecans of the Femoral Head. AB - Osteochondritis dissecans (OCD) of the femoral head is not a common source of hip pain. Hip arthroscopy is becoming a more frequent indication for intra-articular pathologies of the hip. Osteochondral autologous transplantation is a promising technique that theoretically can reconstruct osteochondral lesions of the femoral head. We describe our technique for arthroscopic antegrade osteochondral autologous transplantation for the treatment of OCD of the femoral head. The advantages of this technique include that it is a less invasive method with the ability to assess and treat intra-articular pathologies associated with OCD of the femoral head at same time. Case series and outcomes after this technique are not currently reported in the literature; however, it could be a less invasive method and provide favorable clinical outcomes for patients with OCD lesions of the femoral head. PMID- 26870646 TI - Arthroscopically Assisted Treatment of Acute Dislocations of the Acromioclavicular Joint. AB - Arthroscopically assisted treatments for dislocations of the acromioclavicular joint combine the advantages of exact and visually controlled coracoid tunnel placement with the possibility of simultaneous treatment of concomitant injuries. The clinical results of previous arthroscopically assisted techniques have been favorable at midterm and long-term follow-up. The presented surgical technique combines the advantages of arthroscopically positioned coracoclavicular stabilization with an additional suture cord cerclage of the acromioclavicular joint capsule for improved horizontal stability. PMID- 26870647 TI - Medial Closing-Wedge Distal Femoral Osteotomy: Fixation With Proximal Tibial Locking Plate. AB - Distal femoral varus osteotomy is a well-established procedure for the treatment of lateral compartment cartilage lesions and degenerative disease, correcting limb alignment and decreasing the progression of the pathology. Surgical techniques can be performed with a lateral opening-wedge or medial closing-wedge correction of the deformity. Fixation methods for lateral opening-wedge osteotomies are widely available, and there are various types of implants that can be used for fixation. However, there are currently only a few options of implants for fixation of a medial closing-wedge osteotomy on the market. This report describes a medial, supracondylar, V-shaped, closing-wedge distal femoral osteotomy using a locked anterolateral proximal tibial locking plate that fits anatomically to the medial side of the distal femur. This is a great option as a stable implant for a medial closing-wedge distal femoral osteotomy. PMID- 26870648 TI - Eversion-Inversion Labral Repair and Reconstruction Technique for Optimal Suction Seal. AB - Labral tears are a significant cause of hip pain and are currently the most common indication for hip arthroscopy. Compared with labral debridement, labral repair has significantly better outcomes in terms of both daily activities and athletic pursuits in the setting of femoral acetabular impingement. The classic techniques described in the literature for labral repair all use loop or pass through intrasubstance labral sutures to achieve a functional hip seal. This hip seal is important for hip stability and optimal joint biomechanics, as well as in the prevention of long-term osteoarthritis. We describe a novel eversion inversion intrasubstance suturing technique for labral repair and reconstruction that can assist in restoration of the native labrum position by re-creating an optimal seal around the femoral head. PMID- 26870649 TI - Arthroscopic Hip Labral Reconstruction and Augmentation Using Knotless Anchors. AB - Biomechanical stability is the primary function of the acetabular labrum. It provides a hip suction seal and optimal joint function. Labral tears are a common reason for hip arthroscopy, to improve patient function and to prevent long-term degenerative arthropathy. Arthroscopic labral repair has shown significantly better outcomes in return to premorbid activity levels when compared with labral debridement. Injury to the acetabular labrum is a challenge and can lead to long term complications. In this scenario, arthroscopic labral reconstruction has shown good results regarding patient subjective and objective outcomes. We describe a technique for complete arthroscopic labral reconstruction using tensor fascia lata allograft. PMID- 26870650 TI - Arthroscopic Lysis of Arthrofibrosis of the Fifth Tarsometatarsal Joint. AB - Loss of motion of the fifth tarsometatarsal joint can be a cause of lateral foot pain after Lisfranc fracture-dislocation or fracture of the fifth metatarsal tubercle. Arthroscopic lysis of the joint can be an effective surgical treatment with the advantage of minimal soft-tissue trauma and early vigorous mobilization of the joint. The lysis can be extended to the fourth tarsometatarsal joint and the adjacent tendons if indicated. PMID- 26870651 TI - Arthroscopic Anterior Capsular Reconstruction of the Hip for Recurrent Instability. AB - Symptomatic anterior instability of the hip is typically iatrogenic in nature and poses a challenging problem for the orthopaedist. With early recognition, capsular repair and plication are often effective in restoring stability. Cases involving multiple instability episodes or those with delayed presentation, however, may have patulous and deficient capsular tissue precluding successful capsulorrhaphy. Capsular reconstruction may play an important role in restoring stability in these difficult cases. We present an arthroscopic technique for iliofemoral ligament reconstruction, with Achilles tendon allograft, to address instability of the hip due to anterior capsular deficiency. PMID- 26870652 TI - Primary Frozen Shoulder Syndrome: Arthroscopic Capsular Release. AB - Idiopathic adhesive capsulitis, or primary frozen shoulder syndrome, is a fairly common orthopaedic problem characterized by shoulder pain and loss of motion. In most cases, conservative treatment (6-month physical therapy program and intra articular steroid injections) improves symptoms and restores shoulder motion. In refractory cases, arthroscopic capsular release is indicated. This surgical procedure carries several advantages over other treatment modalities. First, it provides precise and controlled release of the capsule and ligaments, reducing the risk of traumatic complications observed after forceful shoulder manipulation. Second, release of the capsule and the involved structures with a radiofrequency device delays healing, which prevents adhesion formation. Third, the technique is straightforward, and an oral postoperative steroid program decreases pain and allows for a pleasant early rehabilitation program. Fourth, the procedure is performed with the patient fully awake under an interscalene block, which boosts the patient's confidence and adherence to the physical therapy protocol. In patients with refractory primary frozen shoulder syndrome, arthroscopic capsular release emerges as a suitable option that leads to a faster and long-lasting recovery. PMID- 26870654 TI - Creating and Closing the T-Capsulotomy for Improved Visualization During Arthroscopic Treatment of Femoroacetabular Impingement. AB - Treatment of femoroacetabular impingement through an arthroscopic approach has gained widespread popularity in recent years. Although outcomes are generally favorable, one of the most common reasons for failure is incomplete resection of cam lesions of the femoral neck. As a result, the T-capsulotomy has been introduced as a method for improving access to the femoral head-neck junction, which is not always visible through a standard interportal capsulotomy. The T capsulotomy has the benefits of improving arthroscopic visualization of the femoral neck, reducing overall fluoroscopy exposure for the patient and surgeon, and facilitating capsular plication. We present a reliable and efficient method for creating and repairing the T-capsulotomy. We routinely perform this technique in patients with cam lesions that are too large or too distal to safely visualize and decompress through an interportal capsulotomy. PMID- 26870653 TI - Horizontal and Vertical Stabilization of Acute Unstable Acromioclavicular Joint Injuries Arthroscopy-Assisted. AB - We describe the technical aspects of an arthroscopy-assisted procedure indicated for the management of acute unstable acromioclavicular joint injuries, consisting of a synthetic augmentation of both the coracoclavicular and acromioclavicular ligaments, that anatomically reproduces the coracoclavicular biomechanics and offers fixation that keeps the torn ends of the ligaments facing one another, thus allowing healing of the native structures without the need for a second surgical procedure for metal hardware removal. PMID- 26870655 TI - A Simple Technique for Capsular Repair After Hip Arthroscopy. AB - Capsulotomy is typically performed during arthroscopic treatment for femoroacetabular impingement. As the frequency of hip arthroscopy continues to expand rapidly, increased attention is being paid to the implications of interportal capsulotomy and the need for repair. To minimize the risk of postoperative instability, capsular closure has been recommended to restore the anatomy and biomechanical function of the capsule. We present a reliable, efficient, and effective method for arthroscopic closure of the interportal capsulotomy after hip arthroscopy. PMID- 26870656 TI - Anterior Cruciate Ligament Remnant-Preserving Reconstruction Using a "Lasso-Loop" Knot Configuration. AB - Anterior cruciate ligament (ACL) rupture predisposes to altered kinematics and possible knee joint degeneration. Graft fiber maturation and ligamentization may eliminate this risk during ACL reconstruction procedures. ACL remnant-sparing techniques support the theory that the preserved tissue enhances revascularization, preserves the mechanoreceptors, and leads to anatomic remodeling. The purpose of this article is to present a simple and reproducible technique of tensioning the preserved ACL remnant over the femur. A nonabsorbable suture is passed through the ACL remnant with a "lasso-loop" technique using a curved rotator cuff hook. Femoral and tibial tunnel preparation is performed according to a standard surgical technique for the EndoButton device (Smith & Nephew Endoscopy, Andover, MA). The free ends of the ACL remnant suture are retrieved through the tibial tunnel and passed through each outside hole of the EndoButton device. The hamstring graft is passed through the tibial and femoral tunnels and fixed to the femoral cortex by flipping the EndoButton and to the tibia by an interference screw. Finally, non-sliding half-stitch locking knots are made to secure the ACL remnant suture on the EndoButton device, by use of a knot pusher. This technique offers simple and secure tensioning of the ACL remnant on the fixation device. PMID- 26870657 TI - Perineal Post Padding Technique to Improve Hip Distraction in Tall Patients. AB - Hip distraction is necessary for safe arthroscopic entry into the hip joint. Achieving sufficient distraction is difficult in exceedingly tall patients (>190.5 cm) because of size limitations of currently available hip distraction systems. Inadequate distraction can delay the surgical procedure and potentially lead to complications. By repurposing a foam head-positioning block, we report a safe and inexpensive positioning technique for extending the traction distance for tall patients by 2 inches. PMID- 26870658 TI - An unexpected and devastating adverse event of dasatinib: Rhabdomyolysis. AB - We, herein, describe a 52-year-old male whom developed rhabdomyolysis and acute renal failure likely related to dasatinib shortly after the administration of treatment. After withdrawal of dasatinib, the myalgia reduced, and his CK returned to normal levels within a week. On follow-up acute renal failure did resolve without requiring dialysis, but unfortunately the patient died of severe respiratory distress. We recommend that musculoskeletal symptoms should be monitorized during therapy with dasatinib, and CML patients with musculoskeletal symptoms should have CK levels checked in order to prevent this unexpected but devastating adverse event. PMID- 26870659 TI - Four hepatosplenic T-cell lymphoma cases of Japanese patients. AB - Hepatosplenic T-cell lymphoma (HSTCL), a rare type of gammadelta T-cell lymphoma, is characterized by hepatosplenomegaly and cytopenias. It is associated with immunodeficiency and its age of onset is reportedly between the 20s and 30s. We herein report 4 Japanese HSTCL cases. Three of them, including an elderly case that was 74 years of age, were not at adolescence. No cases had a history of immunodeficiency. All other disease phenotypes were similar to the typical HSTCL cases. These findings suggest that there are a certain proportion of HSTCL patients who presented after middle age. PMID- 26870662 TI - Hypothermia associated with clobazam use in adult epilepsy. AB - Clobazam, a 1,5-benzodiazepine FDA-approved in 2011, is commonly used to treat anxiety and epilepsy. It has not associated with hypothermia until very recently, in a case report involving two pediatric patients. Here, we report the first case of hypothermia development in an adult patient with epilepsy associated with clobazam use. A couple months after starting clobazam, the patient started developing episodes of hypothermia every several weeks, with temperatures ranging from 90 degrees F-95 degrees F. Normothermia was achieved with Bair Hugger therapy. Thyroid-stimulating hormone and cortisol levels were normal, and there was no evidence of infection in most instances. After 11 total episodes of hypothermia over a year of clobazam use, the drug was discontinued. It has now been 7 months after discontinuation, and the patient has not experienced any more episodes of hypothermia. Early recognition of the link between clobazam and hypothermia may prevent avoidable Emergency Department visits and hospitalizations. PMID- 26870660 TI - An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome. AB - Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop. PMID- 26870661 TI - Increased frontal sleep slow wave activity in adolescents with major depression. AB - Sleep slow wave activity (SWA), the major electrophysiological characteristic of deep sleep, mirrors both cortical restructuring and functioning. The incidence of Major Depressive Disorder (MDD) substantially rises during the vulnerable developmental phase of adolescence, where essential cortical restructuring is taking place. The goal of this study was to assess characteristics of SWA topography in adolescents with MDD, in order to assess abnormalities in both cortical restructuring and functioning on a local level. All night high-density EEG was recorded in 15 patients meeting DSM-5 criteria for MDD and 15 sex- and age-matched healthy controls. The actual symptom severity was assessed using the Children's Depression Rating Scale-Revised (CDRS-R). Topographical power maps were calculated based on the average SWA of the first non-rapid eye movement (NREM) sleep episode. Depressed adolescents exhibited significantly more SWA in a cluster of frontal electrodes compared to controls. SWA over frontal brain regions correlated positively with the CDRS-R subscore "morbid thoughts". Self reported sleep latency was significantly higher in depressed adolescents compared to controls whereas sleep architecture did not differ between the groups. Higher frontal SWA in depressed adolescents may represent a promising biomarker tracing cortical regions of intense use and/or restructuring. PMID- 26870664 TI - Compliance to Care Guidelines for Duchenne Muscular Dystrophy. AB - BACKGROUND: International care guidelines for Duchenne muscular dystrophy (DMD) were published in 2010, but compliance in clinical practice is unknown. OBJECTIVE: The objective of our study was to compare real-world DMD care in Germany, Italy, the UK, and the US with the clinical recommendations. METHODS: DMD patients from Germany, Italy, the UK, and the US were identified through Translational Research in Europe - Assessment & Treatment of Neuromuscular Diseases (TREAT-NMD) registries and invited with a caregiver to complete a questionnaire with questions regarding DMD-related healthcare. Estimates of care were stratified by disease stage (early/late ambulatory/non-ambulatory) and compared against the care guidelines. RESULTS: A total of 770 patients (173 German, 122 Italian, 191 UK, and 284 US) completed the questionnaire. Poor compliance to guidelines of routine follow-up by neuromuscular, cardiac, and respiratory specialists, physiotherapy, and access to medical devices and aids were observed in all countries. Less than 27% (209 of 770) of patients met all absolute recommendations, ranging from 9% (11 of 122) in Italy to 37% (70 of 191) in the UK, and from 49% (76 of 155) in the early ambulatory class to 16% (33 of 205) in the late non-ambulatory class. CONCLUSIONS: We show that the medical management of DMD varies substantially between Germany, Italy, the UK, and the US. Experience of real-world DMD care appears to be in poor agreement with the DMD clinical guidelines and increased compliance is urgently needed to improve treatment outcomes and enable patients to lead fulfilling, independent lives into adulthood. PMID- 26870663 TI - Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. AB - BACKGROUND AND OBJECTIVE: Congenital myasthenic syndromes are rare inherited disorders characterized by fatigable weakness caused by malfunction of the neuromuscular junction. We performed whole exome sequencing to unravel the genetic aetiology in an English sib pair with clinical features suggestive of congenital myasthenia. METHODS: We used homozygosity mapping and whole exome sequencing to identify the candidate gene variants. Mutant protein expression and function were assessed in vitro and a knockdown zebrafish model was generated to assess neuromuscular junction development. RESULTS: We identified a novel homozygous missense mutation in the SLC25A1 gene, encoding the mitochondrial citrate carrier. Mutant SLC25A1 showed abnormal carrier function. SLC25A1 has recently been linked to a severe, often lethal clinical phenotype. Our patients had a milder phenotype presenting primarily as a neuromuscular (NMJ) junction defect. Of note, a previously reported patient with different compound heterozygous missense mutations of SLC25A1 has since been shown to suffer from a neuromuscular transmission defect. Using knockdown of SLC25A1 expression in zebrafish, we were able to mirror the human disease in terms of variable brain, eye and cardiac involvement. Importantly, we show clear abnormalities in the neuromuscular junction, regardless of the severity of the phenotype. CONCLUSIONS: Based on the axonal outgrowth defects seen in SLC25A1 knockdown zebrafish, we hypothesize that the neuromuscular junction impairment may be related to pre synaptic nerve terminal abnormalities. Our findings highlight the complex machinery required to ensure efficient neuromuscular function, beyond the proteomes exclusive to the neuromuscular synapse. PMID- 26870665 TI - Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy. AB - BACKGROUND: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. OBJECTIVE: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. METHOD: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. RESULTS: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. CONCLUSIONS: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID- 26870666 TI - Congenital Myasthenic Syndromes with Predominant Limb Girdle Weakness. AB - Congenital myasthenic syndromes are a heterogeneous group of genetically determined disorders characterized by impaired neuromuscular transmission. They usually present from birth to childhood and are characterised by exercise induced weakness and fatigability. Genotype-phenotype correlations are difficult. However, in some patients particular phenotypic aspects may point towards a specific genetic defect. The absence of ptosis and ophthalmoparesis in patients with limb-girdle weakness makes the diagnosis of a neuromuscular transmission defect particularly challenging (LG-CMS). This is illustrated by a well documented case published by Walton in 1956. The diagnosis of LG-CMS is secured by demonstrating a neuromuscular transmission defect with single fibre EMG or repetitive nerve stimulation, in the absence of auto-antibodies. Ultimately, a genetic test is required to identify the underlying cause and assure counselling and optimization of treatment. LG-CMS are inherited in autosomal recessive traits, and are often associated with mutations in DOK7 and GFPT1, and less frequently with mutations in COLQ, ALG2, ALG14 and DPAGT. Genetic characterization of CMS is of the upmost importance when choosing the adequate treatment. Some of the currently used drugs can either ameliorate or aggravate the symptoms depending on the underlying genetic defect. The drug most frequently used for the treatment of CMS is pyridostigmine an acetylcholinesterase inhibitor. However, pyridostigmine is not effective or is even detrimental in DOK7- and COLQ-related LG-CMS, while beta-adrenergic agonists (ephedrine, salbutamol) show some sustained benefit. Standard clinical trials may be difficult, but standardized follow-up of patients and international collaboration may help to improve the standards of care of these conditions. PMID- 26870667 TI - Dispensing apparatus for use in a cued food delivery task. AB - Neurobiological models of obesity postulate that obese individuals have difficulty regulating food intake partly because they attribute excessive salience to stimuli signaling food availability. Typically, human studies that investigate the relationship between brain responses to food-related stimuli and obesity present food cues without subsequent delivery of food. However, in order to identify the brain correlates of cue reactivity, we must record brain responses to food-related cues signaling food availability. Therefore, we have developed a dispensing apparatus for use in a cued-food delivery task in which event-related potentials (ERPs) to food-related images predicting food delivery and images not predicting food delivery can be recorded. Here, we describe a method where:*The experimental apparatus dispenses an edible item (i.e., a chocolate candy) which may or may not be eaten, or a non-edible control item (e.g., a plastic bead).*Deposit boxes are available to store uneaten candies and the non-edible control items.*The dispensing mechanism is capable of recording the exact timestamp when each delivery event occurs (e.g., release from the dispenser, arrival in the receptacle, storage in the deposit box). PMID- 26870668 TI - Analysis of hair cortisol levels in captive chimpanzees: Effect of various methods on cortisol stability and variability. AB - Hair cortisol has been reported to be a useful measure of long-term hypothalamic pituitary-adrenal (HPA) axis activation in several species. It serves as a practical tool for long-term stress assessment, but it is important to understand the methodological factors that can affects hair cortisol assays to avoid methodological artifacts. To that end, we tested several procedures for measuring cortisol levels in hair collected from captive chimpanzees. The results showed that reproducibility was high, and we found no differences in cortisol levels among the various storage, drying, and sampling methods. However, the fineness of homogenized hair, sample weight, and extraction time affected absolute hair cortisol concentration. Although hair cortisol levels were stable over time, factors that may influence measurement results should be kept constant throughout a study.*We modified and validated a methodology involving enzyme immunoassays to reliably measure the hair cortisol levels of captive chimpanzees.*The results revealed that the fineness of homogenized hair, sample weight, and extraction time caused variations in absolute hair cortisol concentrations in chimpanzees. In contrast, storage, drying, and sampling from similar body parts did not affect the results. PMID- 26870670 TI - Modelling the prevalence of hepatitis C virus amongst blood donors in Libya: An investigation of providing a preventive strategy. AB - AIM: To determine hepatitis C virus (HCV) seroprevalence among the Libyan population using blood donors and applying the autoregressive integrated moving average (ARIMA) model to predict future trends and formulate plans to minimize the burden of HCV infection. METHODS: HCV positive cases were collected from 1008214 healthy blood donors over a 6-year period from 2008 to 2013. Data were used to construct the ARIMA model to forecast HCV seroprevalence among blood donors. The validity of the model was assessed using the mean absolute percentage error between the observed and fitted seroprevalence. The fitted ARIMA model was used to forecast the incidence of HCV beyond the observed period for the year 2014 and further to 2055. RESULTS: The overall prevalence of HCV among blood donors was 1.8%, varying over the study period from 1.7% to 2.5%, though no significant variation was found within each calendar year. The ARIMA model showed a non-significant auto-correlation of the residuals, and the prevalence was steady within the last 3 years as expressed by the goodness-of-fit test. The forecast incidence showed an increase in HCV seropositivity in 2014, ranging from 500 to 700 per 10000 population, with an overall prevalence of 2.3%-2.7%. This may be extended to 2055 with minimal periodical variation within each 6-year period. CONCLUSION: The applied model was found to be valuable in evaluating the seroprevalence of HCV among blood donors, and highlighted the growing burden of such infection on the Libyan health care system. The model may help in formulating national policies to prevent increases in HCV infection and plan future strategies that target the consequences of the infection. PMID- 26870671 TI - Pathogenicity of a currently circulating Chinese variant pseudorabies virus in pigs. AB - AIM: To test the pathogenicity of pseudorabies virus (PRV) variant HN1201 and compare its pathogenicity with a classical PRV Fa strain. METHODS: The pathogenicity of the newly-emerging PRV variant HN1201 was evaluated by different inoculating routes, virus loads, and ages of pigs. The classical PRV Fa strain was then used to compare with HN1201 to determine pathogenicity. Clinical symptoms after virus infection were recorded daily and average daily body weight was used to measure the growth performance of pigs. At necropsy, gross pathology and histopathology were used to evaluate the severity of tissue damage caused by virus infection. RESULTS: The results showed that the efficient infection method of RPV HN1201 was via intranasal inoculation at 10(7) TCID50, and that the virus has high pathogenicity to 35- to 127-d old pigs. Compared with Fa strain, pigs infected with HN1201 showed more severe clinical symptoms and pathological lesions. Immunochemistry results revealed HN1201 had more abundant antigen distribution in extensive organs. CONCLUSION: All of the above results suggest that PRV variant HN1201 was more pathogenic to pigs than the classical Fa strain. PMID- 26870669 TI - Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication. AB - Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. One of HSV-1 alpha (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID- 26870672 TI - Neuropathology of JC virus infection in progressive multifocal leukoencephalopathy in remission. AB - AIM: To investigate the neuropathology of the brain in a rare case of remission following diagnosis of progressive multifocal leukoencephalopathy (PML). METHODS: Consent from the family for an autopsy was obtained, clinical records and radiograms were retrieved. A complete autopsy was performed, with brain examination after fixation and coronal sectioning at 1 cm intervals. Fourteen regions were collected for paraffin embedding and staining for microscopic analysis. Histologic sections were stained with Luxol blue, hematoxylin/eosin, and immunostained for myelin basic protein, neurofilament, SV40 T antigen and p53. The biopsy material was also retrieved and sections were stained with hematoxylin/eosin and immunostained for SV40 and p53. Sections were examined by American Board of Pathology certified pathologists and images captured digitally. RESULTS: Review of the clinical records was notable for a history of ulcerative colitis resulting in total colectomy in 1977 and a liver transplant in 1998 followed by immune-suppressive therapy. Neurological symptoms presented immediately, therefore a biopsy was obtained which was diagnosed as PML. Immunotherapy was adjusted and clinical improvement was noted. No subsequent progression was reported. Review of the biopsy demonstrated atypical astrocytes and enlarged hyperchromatic oligodendroglial cells consistent with JC virus infection. Strong SV40 and p53 staining was found in glial cells and regions of dense macrophage infiltration were present. On gross examination of the post mortem brain, a lesion in the same site as the original biopsy in the cerebellum was identified but no other lesions in the brain were found. Microscopic analysis of this cerebellar lesion revealed a loss of myelin and axons, and evidence of axonal damage. This single burned-out lesion was equivocally positive for SV40 antigen with little p53 staining. Examination of thirteen other brain regions found no other occult sites. CONCLUSION: Our study reveals residual damage, rare macrophages or other inflammation and minimal evidence of persistent virus. This case demonstrates the possibility of complete remission of PML. PMID- 26870673 TI - Rosa damascena as holy ancient herb with novel applications. AB - Rosa damascena as an ornamental plant is commonly known as "Gole Mohammadi" in Iran. Iranian people have been called this plant, the flower of Prophet "Mohammad". R. damascena is traditionally used for treatment of abdominal and chest pains, strengthening the heart, menstrual bleeding, digestive problems and constipation. This paper reviews the ethnopharmacology, phytochemistry and pharmaceutical investigations on R. damascena. All relevant databases and local books on ethnopharmacology of R. damascena were probed without limitation up to 31st March 2015 and the results of these studies were collected and reviewed. R. damascena has an important position in Iranian traditional medicine. It is economically a valuable plant with therapeutic applications in modern medicine. The antimicrobial, antioxidant, analgesic, anti-inflammatory, anti-diabetic and anti-depressant properties of R. damascena have been confirmed. Citronellol and geraniol as the main components of R. damascena essential oil are responsible for pharmacological activities. Overall, R. damascena as holy ancient plant with modern pharmacological investigations should be more investigated as traditional uses in large preclinical and clinical studies. PMID- 26870674 TI - Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content. AB - Beetroot ( tian cai) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription-polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID- 26870675 TI - Effects of auditory stimulation with music of different intensities on heart period. AB - Various studies have indicated that music therapy with relaxant music improves cardiac function of patients treated with cardiotoxic medication and heavy-metal music acutely reduces heart rate variability (HRV). There is also evidence that white noise auditory stimulation above 50 dB causes cardiac autonomic responses. In this study, we aimed to evaluate the acute effects of musical auditory stimulation with different intensities on cardiac autonomic regulation. This study was performed on 24 healthy women between 18 and 25 years of age. We analyzed HRV in the time [standard deviation of normal-to-normal RR intervals (SDNN), percentage of adjacent RR intervals with a difference of duration >50 ms (pNN50), and root-mean square of differences between adjacent normal RR intervals in a time interval (RMSSD)] and frequency [low frequency (LF), high frequency (HF), and LF/HF ratio] domains. HRV was recorded at rest for 10 minutes. Subsequently, the volunteers were exposed to baroque or heavy-metal music for 5 minutes through an earphone. The volunteers were exposed to three equivalent sound levels (60-70, 70-80, and 80-90 dB). After the first baroque or heavy-metal music, they remained at rest for 5 minutes and then they were exposed to the other music. The sequence of songs was randomized for each individual. Heavy metal musical auditory stimulation at 80-90 dB reduced the SDNN index compared with control (44.39 +/- 14.40 ms vs. 34.88 +/- 8.69 ms), and stimulation at 60-70 dB decreased the LF (ms(2)) index compared with control (668.83 +/- 648.74 ms(2) vs. 392.5 +/- 179.94 ms(2)). Baroque music at 60-70 dB reduced the LF (ms(2)) index (587.75 +/- 318.44 ms(2) vs. 376.21 +/- 178.85 ms(2)). In conclusion, heavy metal and baroque musical auditory stimulation at lower intensities acutely reduced global modulation of the heart and only heavy-metal music reduced HRV at higher intensities. PMID- 26870676 TI - Exploratory studies on the therapeutic effects of Kumarabharana Rasa in the management of chronic tonsillitis among children at a tertiary care hospital of Karnataka. AB - The effect of an Ayurvedic poly-herbo-mineral formulation Kumarabharana Rasa (KR) in the management of chronic tonsillitis (Tundikeri) in children has been assessed in this study. This clinical study was a double-arm study with a pre- and post-test design at the outpatient level in a tertiary Ayurveda hospital attached to a teaching institute located in district headquarters in Southern India. Patients (n = 40) with chronic tonsillitis satisfying diagnostic criteria and aged between 5 and 10 years were selected from the outpatient Department of Kaumarbhritya, SDM College of Ayurveda and Hospital, Hassan. Among them, 20 patients were treated with Kumarabharana rasa (tablet form) at a dose of 500 mg once daily for 30 days (Group A). The other 20 patients were treated with Godhuma Vati (placebo) at a dose of 500 mg once daily for 30 days (Group B). In both groups, Madhu was the Anupana advised. After completion of 30 days of treatment, the patients were assessed on the following day and another investigation took place 15 days later. Statistically significant effects (p < 0.05) in the reduction of all signs and symptoms of chronic tonsillitis after KR treatment were observed. These results indicate that Kumarabharana Rasa has an ameliorative effect in reducing the signs and symptoms of chronic tonsillitis. PMID- 26870677 TI - Immediate effect of yogic visual concentration on cognitive performance. AB - The ancient Indian yoga text, Hatha Yoga Pradipika, describes six cleansing techniques. The objective of cleansing techniques is to purify and prepare the body for the practice of yoga postures, breath regulation, and meditation. Yogic visual concentration technique (trataka) is one of these techniques. A previous study showed an increase in critical flicker fusion (CFF) following yogic visual concentration (trataka). The present study planned to assess the immediate effect of trataka on cognitive performance using the Stroop color-word test. Performance on the Stroop color-word test was assessed in 30 healthy male volunteers with ages ranging from 18 years to 31 years old (22.57 +/- 3.65 years). The participants were tested before and after yogic visual concentration (trataka) and during a control session on two separate days. There was a significant improvement in performance on the Stroop color-word test after trataka compared to the control session [repeated measures analysis of variance (RM ANOVA) with Bonferroni adjustment; p < 0.001]. Performance on the Stroop color-word test was better after trataka compared to the control session suggesting that the trataka technique increased the selective attention, cognitive flexibility, and response inhibition. PMID- 26870678 TI - Efficacy of Dragon's blood cream on wound healing: A randomized, double-blind, placebo-controlled clinical trial. AB - The blood-red sap of Dragon's blood has been used in folk medicine for fractures, wounds, inflammation, gastrointestinal disorders, rheumatism, blood circulation dysfunctions, and cancer. Existing in vitro and in vivo bioactivity of this herb on different mechanisms of healing shows strong potential of this sap in wound healing. This clinical trial study was designated to evaluate the wound healing effect of Dragon's blood on human wounds. Sixty patients, between the ages of 14 65 years, who were referred to remove their skin tag, were assigned to this double-blind, placebo-controlled, randomized clinical trial and received either Dragon's blood or a placebo cream. They were visited on the 3rd, 5th, 7th, 10th, 14th, and 20th day of the trial to check the process of healing and to measure the wound's surface. At the end of trial, there was a significant difference in the mean duration of wound healing between the two groups (p = 0.0001). The phenolic compounds and the alkaloid taspine, which exist in Dragon's-blood resin, are probably the main reasons for the wound healing property of this plant. Being natural accessible, safe, and affordable makes Dragon's blood cream, a good choice for addition to the wound healing armamentarium. Further studies on wounds with different causes and among larger populations are suggested to ensure the effectiveness and safety of Dragon's blood. PMID- 26870679 TI - Isolation and characterization of bioactive components from Mirabilis jalapa L. radix. AB - The present investigation was carried out to isolate and characterize bioactive components from Mirabilis jalapa L. radix ( zi mo li gen). Thin-layer chromatography was used for the separation of spots from fractions of the crude extract. Separated spots were collected for identification of their activities. Free-radical scavenging activity was evaluated by spraying thin-layer chromatography plates (spotted with fractions) with 0.2% of 2,2-diphenyl-1 picrylhydrazyl solution. Activity against human pathogens such as Staphylococcus aureus and Candida albicans were determined using the agar diffusion method. Potential spots were subjected to infrared (IR) analysis and gas chromatography for characterization. Two spots (5F1 and 1F3) showed free-radical scavenging activity. The 1F3 spot was active against both S. aureus and C. albicans, whereas the 5F1 spot was active against S. aureus only. IR spectral analysis indicated that 5F1 spot to be a triterpenoid. Using IR spectral analysis and an IR library search, the 1F3 spot was identified to be a flavone, which may have a hydroxyl group in ring "A" of the flavone nucleus. Our results indicated that the 1F3 and 5F1 spots are potential free-radical scavengers. Both 1F3 and 5F1 exhibited antimicrobial activity. IR spectral analysis coupled with an IR library search indicated 1F3 and 5F1 to be a flavone and a triterpenoid, respectively. PMID- 26870680 TI - Antcin K, an active triterpenoid from the fruiting bodies of basswood cultivated Antrodia cinnamomea, induces mitochondria and endoplasmic reticulum stress mediated apoptosis in human hepatoma cells. AB - Liver cancer is the second leading cause of cancer deaths in Taiwan as per the 2011 statistics and ranks fourth in cancer-related mortality in the world. Recent researches have shown that Antrodia cinnamomea, a Taiwan-specific medicinal mushroom, has biological activities, including hepatoprotection, anti inflammation, antihepatitis B virus activity, and anticancer activity. In the present study, the antiproliferative activity and molecular mechanisms of antcin K, the most abundant ergostane triterpenoid from the fruiting bodies of basswood cultivated A. cinnamomea, were investigated using human hepatoma Hep 3B cells. The results showed that antcin K effectively reduced Hep 3B cells viability within 48 hours. Antcin K induced phosphatidylserine exposure, chromatin condensation, and DNA damage, but did not significantly increase autophagosome content or cause cell expansion and cell lysis. Thus, the principal mode of Hep 3B cells death induced by antcin K was apoptosis, rather than autophagy or necrosis. In-depth investigation of the molecular mechanisms revealed that antcin K first promoted reactive oxygen species generation and adenosine triphosphate depletion, leading to endoplasmic reticulum stress and resulting in mitochondrial membrane permeability changes. After losing the mitochondrial membrane potential, caspase-independent and caspase-dependent apoptosis-related proteins were released, including HtrA2, apoptotic-induced factor, endonuclease G, and cytochrome c. Cytochrome c activated caspase-9 and caspase-3, and cut downstream protein PARP, ultimately leading to cell apoptosis. These results suggested that antcin K induced mitochondrial and endoplasmic reticulum stress-mediated apoptosis in human hepatoma cells. Coupled with these findings, antcin K has a potential to be a complementary agent in liver cancer therapy. PMID- 26870681 TI - Effects of the natural compounds embelin and piperine on the biofilm-producing property of Streptococcus mutans. AB - We aimed to evaluate the effects of the natural compounds embelin and piperine on the biofilm-formation property of Streptococcus mutans. A total of 30 clinical isolates were identified as S. mutans and screened for biofilm formation using the microtiter plate method. The strongest biofilm producer (SM03) was used for identifying both minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC). We subsequently used this concentration against each of the strong biofilm producer isolates at A 492 < 0.5 optical density (OD). Of the 30 isolates screened for biofilm formation, 18 isolates showed strong biofilm formation, 09 isolates showed moderate formation, and 03 isolates showed poor/nonbiofilm formation. The MIC of embelin for the strongest biofilm producer (SM03) was 0.55 +/- 0.02, whereas that of piperine was 0.33 +/- 0.02. The MBIC of embelin was 0.0620 +/- 0.03, whereas that of piperine was 0.0407 +/- 0.03, which was lower than that of embelin. At OD492 < 0.5, the MBIC of both compounds significantly inhibited biofilm formation of all the 18 strong biofilm-forming isolates. The results of this study demonstrate a significant antibiofilm effect of the natural compounds embelin and piperine, which can contribute towards the development of a database for novel drug candidates for treating oral infections caused by S. mutans. PMID- 26870682 TI - Comparison of efficacy of alternative medicine with allopathy in treatment of oral fungal infection. AB - This clinical study assessed and compared the efficacy of tea tree oil (TTO), an alternative form of medicine, with clotrimazole (i.e., allopathy) and a conservative form of management in the treatment of oral fungal infection. In this interventional, observational, and comparative study, we enrolled 36 medically fit individuals of both sexes who were aged 20-60 years old. The participants were randomly assigned to three groups. Group I was given TTO (0.25% rinse) as medicament, Group II was given clotrimazole, and Group III was managed with conservative treatment. The results were analyzed from the clinical evaluation of lesions, changes in four most common clinical parameters of lesions, and subjective symptoms on periodic follow-up. Based on the results, the percentage efficiency of the two groups were taken and compared through a bar graph on the scale of 1. No toxicity to TTO was reported. Group I (TTO) was found to be more efficient than the other two groups, as changes in four parameter indices of lesions were noted, and results for all three groups were compared on a percentage basis. The study concluded that TTO, being a natural product, is a better nontoxic modality compared to clotrimazole, in the treatment of oral fungal infection and has a promising future for its potential application in oral health products. PMID- 26870684 TI - Quality standards for Hutabhugadi curna (Ayurvedic Formulary of India). AB - In India, herbal medicines are mainly based on the Ayurvedic system. The main drawback of traditional medicines is a lack of standardized products. Standardization of any herbal formulation is essential in order to assess the quality, purity, safety, and efficacy of drugs based on the analysis of their active properties. Testing of Ayurvedic preparations using scientific methodologies will add to quality and authenticity of the product. This article reports standardization parameters for Hutabhugadi curna (HC) used traditionally in the treatment of Agnimandya (digestive impairment), Pandu (anemia), Sopha (edema), and Arsa (piles). The formulation was prepared as per Ayurvedic Formulary of India, and it was standardized by organoleptic characterization, macro-microscopic evaluation, physicochemical testing, and thin-layer chromatography/high-performance thin-layer chromatography profiling employing a standard methodology. Results of the experiments conducted provided diagnostic characteristics to identify and standardize the formulation prepared using official ingredients of HC. Based on the data obtained, a monograph on quality standards for HC is proposed. The monograph based on the present investigation results would serve as a document to control the quality of HC. PMID- 26870683 TI - Effects of white rice containing enriched gamma-aminobutyric acid on blood pressure. AB - Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter with beneficial effects including antihypertension and antistress properties. In this study, we examined the effects of GABA-enriched white rice (GABA rice) on blood pressure (BP) in 39 mildly hypertensive adults in a randomized, double-blind, placebo controlled study. The participants were divided into a test group (n = 22) who consumed rice with 11.2 mg GABA/100 g of rice and a placebo group (n = 17) who consumed rice with 2.7 mg GABA/100 g of rice. For 8 weeks, the participants took 150 g of either the GABA rice or the placebo rice. Hematological examinations were performed on both groups at 0, 4, and 8 weeks after the start of rice consumption. Home BP was self-measured two times daily, morning and evening, from 1 weeks before to 2 weeks after the intervention. Although the hospital BP and evening BP measurements of the participants showed no significant change, consumption of the GABA rice improved the morning BP compared with the placebo rice after the 1(st) week and during the 6(th) and 8(th) weeks. These results showed the possibility that the GABA rice improves morning hypertension. PMID- 26870685 TI - Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines. AB - Medicinal plants are noted for their many advantages including the ability to treat diseases such as cancer. In this study, we examined the antitumor effect of the medicinal plant Nigella sativa on the morphology, survival, and apoptosis of ACHN (human renal adenocarcinoma) and GP-293 (normal renal epithelial) cell lines. From a hydroalcoholic extract of N. sativa, n-hexane and ethyl acetate fractions were extracted. Cells were treated with various concentrations of total hydroalcholic extract and n-hexane and ethyl acetate fractions; cell viability, morphological changes, and apoptosis were then determined. Results were presented as mean +/- standard error of the mean (SEM). One-way analysis of variance (ANOVA) was applied for the statistical analysis of the data. The total extract and the fractions in a dose- and time-dependent manner reduced the cell viability in ACHN with no effect on the GP-293 cell line. In addition, the total extract resulted in more morphological changes in the ACHN cells compared to the GP-293 cells. The effect of the total extract in inducing apoptosis after 48 hours in the ACHN cell line was greater than in GP-293. In addition, the effect of the two fractions was lower than the total extract at all used concentrations. Therefore, the effect of total extract and n-hexane and ethyl acetate fractions of N. sativa on cell viability and apoptosis in the ACHN cell line is greater than in the GP 293 cell line. However, the effect of the total extract is higher than either of the two fractions on their own. PMID- 26870686 TI - Exploration of the anticandidal mechanism of Cassia spectabilis in debilitating candidiasis. AB - Candida albicans has become resistant to the commercially available, toxic, and expensive anti-Candida agents that are on the market. These factors force the search for new antifungal agents from natural resources. Cassia spectabilis had been traditionally employed by healers for many generations. The possible mechanisms of the C. spectabilis leaf extract were determined by potassium leakage study and the effect of the extract on the constituents of the cell wall and enzymes as well as the morphological changes on C. albicans cells were studied along with cytotoxicity assays. The cytotoxicity result indicated that the extract is nontoxic as was clearly substantiated by a half maximal inhibitory concentration (IC50) value of 59.10 MUg/mL. The treated cells (C. spectabilis extract) demonstrated potassium leakage of 1039 parts per million (ppm) compared to Amphotericin B (AmpB)-treated cells with a released potassium value of 1115 ppm. The effects of the extract on the cell wall proteins illustrated that there were three major types of variations in the expression of treated cell wall proteins: the presence of new proteins, the absence of proteins, and the amount of expressed protein. The activities of two enzymes, alpha-glucosidase and proteinase, were determined to be significantly high, thereby not fully coinciding with the properties of the antifungal reaction triggered by C. spectabilis. The morphology of C. albicans cells treated with the C. spectabilis extract showed that the cells had abnormalities and were damaged or detached within the microcolonies. Our study verifies C. spectabilis leaf extract as an effective anti-C. albicans agent. PMID- 26870687 TI - Preparation and chemical characteristics of Karunguruvai Khadi used in the traditional Siddha formulation of herbo-mineral-based medicine. AB - INTRODUCTION: Khadi is an extract that has been used in the preparation of Pooneeru (muppu) in Siddha medicine, but it has not been scientifically evaluated for modern medicinal purposes. The present study examines the preparation and chemical composition of Khadi. MATERIALS AND METHODS: According to the method of the palm leaf literature, Karunguruvai and Samba paddy grains were selected for the preparation of Khadi. After removing the husk of the paddies, the cleaned Karunguruvai and Samba rice were processed according to the methods of Swami and Ramasamy Khon. The processed Khadi of Karunguruvai and Samba were analyzed for chemical constituents and were microbiologically assessed. The chemical composition of the paddy grains was also evaluated to compare with the Khadi constituents. RESULTS: The major elements of the paddy grains of Karunguruvai and Samba were calcium (CaO) and sodium (Na2O). The predominant trace elements in the Samba rice were nickel and cadmium, whereas Karunguruvai rice contained arsenic, nickel, copper, and cadmium. Samba Khadi contained the trace elements mercury, chromium, lead, copper, and cobalt, whereas Karunguruvai Khadi had a high content of mercury, vanadium, arsenic, nickel, copper, cadmium, barium, and strontium. Karunguruvai Khadi also contained silicon dioxide (SiO2), aluminum oxide (Al2O3), iron oxide (FeO), manganese oxide (MnO), calcium oxide (CaO), and sodium carbonate (Na2O). By contrast, Samba Khadi contained only ferrous oxide (FeO), calcium oxide (CaO), sulfur dioxide (SO2), and carbon dioxide (CO2), which were chemical constituents of the Samba rice. DISCUSSION: The composition of Karunguruvai rice was compared with Samba rice and it is identified the absence of heavy metals in Samba as well as Karunguruvai rice. Both of rice powders have more or less similar chemical compounds except phosphorous content. Karunguruvai rice possesses more CaO than Samba rice. The bacterial and fungal activities were assessed during the different stages of Khadi preparation-no activities were found in any form of the Khadi. This suggests that Khadi may have a preventive effect against fungal and bacterial infections. CONCLUSION: The result of the chemical analysis of Khadi extracts showed that Khadi prepared from the Karunguruvai paddy grains (rice) was the best base solvent for ion exchange in the preparation of muppu than Samba Khadi. The analysis of the composition of these two types of Karunguruvai Khadi show that it is a good solvent for the elimination of heavy metals and for the enrichment of elements in Pooneeru powder (muppu), the chuurnam of Siddha drugs. These characteristics enhance the therapeutic potential and safety of the drugs for healing chronic diseases. PMID- 26870688 TI - Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria. AB - The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy. PMID- 26870689 TI - Ethnoveterinary medicine of the Shervaroy Hills of Eastern Ghats, India as alternative medicine for animals. AB - The Eastern Ghats of India is well known for its wealth of natural vegetation and Shervaroy is a major hill range of the Eastern Ghats of Tamil Nadu. Ethnomedicinal studies in the Eastern Ghats of Tamil Nadu or the Shervaroy Hills have been carried out by various researchers. However, there is not much information available on ethnoveterinary medicine in the Eastern Ghats of India. The aim of this study was to examine the potential use of folk plants as alternative medicine for cattle to cure various diseases in the Shervaroy Hills of the Eastern Ghats. Based on interactions with traditional medicine practitioners, it has been observed that a total of 21 medicinal plants belonging to 16 families are used to cure various diseases such as mastitis, enteritis, arthritis, stomatitis, salivation from the mouth, wounding, and conjunctivitis in animals. It has been observed that the traditional knowledge of ethnoveterinary medicine is now confined only among the surviving older people and a few practitioners in the tribal communities of the Shervaroy Hills. Unfortunately, no serious attempts have been made to document and preserve this immense treasure of traditional knowledge. PMID- 26870690 TI - Clinical efficacy and tolerability of Gosha-jinki-gan, a Japanese traditional herbal medicine, for nocturia. AB - We evaluated the efficacy and tolerability of Gosha-jinki-gan (GJG; ji sheng shen qi wan) in 30 cases of nocturia ( ye niao) unresponsive to alpha1-blockers or antimuscarinic drugs. All patients received GJG extract powder (2.5 g) three times a day for 12 weeks as an add-on therapy to alpha1-blockers or antimuscarinic drugs. Subjective outcomes assessed by the International Prostate Symptom Score-quality of life, and the benign prostatic hyperplasia impact index and objective outcomes assessed by urinary frequency and the urine production rate at night showed significant improvement after treatment. Moreover, other objective outcomes assessed by maximum flow rates, postvoid residual, serum human atrial natriuretic peptide levels, and urinary 8-hydroxy-2'-deoxyguanosine levels did not change. Adverse events were observed in 10% of cases; however, these events were mild. GJG appears to be a safe and effective potential therapeutic alternative for patients with nocturia unresponsive to alpha1-blockers or antimuscarinic drugs. Further clinical investigations are required to elucidate the precise pathophysiologic mechanisms of GJG in nocturia. PMID- 26870691 TI - Effect of Coleus forskohlii and its major constituents on cytochrome P450 induction. AB - Coleus forskohlii Briq. has been used traditionally for the treatment of several ailments since antiquity in Ayurveda. In the present study, an approach has been made to evaluate the effect of C. forskohlii and its major constituents on cytochrome P450 (CYP3A, CYP2B, and CYP2C) mRNA expression in rat hepatocytes. To gain better understanding of the herb-drug interaction potential of the chemical constituents present in C. forskohlii, the extract was subjected to column chromatography followed by standardization with respect to forskolin, 1 deoxyforskolin, and 1,9-dideoxyforskolin using reversed-phase high-performance liquid chromatography (RP-HPLC). Hepatocytes were treated with extracts, fractions, and phytoconstituents, followed by extraction and purification of total mRNA. Study of mRNA expression was carried out through reverse transcription polymerase chain reaction, followed by agarose gel electrophoresis. Results revealed that the test substances did not show any significant mRNA expression compared to the control against CYP3A, CYP2B, and CYP2C. Positive controls such as dexamethasone and rifampin showed significantly high (p < 0.001) induction potential compared to the control. It can be concluded that C. forskohlii and its major constituents may not be involved in CYP450 induction based drug interaction. PMID- 26870692 TI - Report from the Second International Conference of Traditional and Complementary Medicine on Health 2015. AB - The Second International Conference of Traditional and Complementary Medicine on Health was held from October 24th through 27th at the GIS National Taiwan University Convention Center in Taipei. Twenty-seven invited speakers, representative of fourteen Countries, delivered their lecture in front of an audience of more than two hundreds of attendees. In addition, a poster exhibition with seventy-two presenters completed the scientific sessions. The leitmotif of the Conference was to promote a common platform in which all medical knowledge is integrated to improve the health care system. Traditional medicine and complementary medicine are characterized by a holistic approach to prevent and cure diseases, making use of natural products and/or physical manipulations. In this context, the Conference emphasized the importance of the Quality Control and of standardized methods for the authentication, preparation and characterization of the herbal products and nutrient supplements, as well as the need for controlled clinical trials and for experimental studies to demonstrate the efficacy and to understand the underlying mechanisms of the preventive and curative treatments. In this report, we highlight the novel findings and the perspectives in Traditional and Complementary Medicine (TCM; chuan tong ji hu bu yi xue) that emerged during the conference. PMID- 26870693 TI - First Images of a Three-Layer Compton Telescope Prototype for Treatment Monitoring in Hadron Therapy. AB - A Compton telescope for dose monitoring in hadron therapy is under development at IFIC. The system consists of three layers of LaBr3 crystals coupled to silicon photomultiplier arrays. (22)Na sources have been successfully imaged reconstructing the data with an ML-EM code. Calibration and temperature stabilization are necessary for the prototype operation at low coincidence rates. A spatial resolution of 7.8 mm FWHM has been obtained in the first imaging tests. PMID- 26870694 TI - Potential of Induced Metabolic Bioluminescence Imaging to Uncover Metabolic Effects of Antiangiogenic Therapy in Tumors. AB - Tumor heterogeneity at the genetic level has been illustrated by a multitude of studies on the genomics of cancer, but whether tumors can be heterogeneous at the metabolic level is an issue that has been less systematically investigated so far. A burning-related question is whether the metabolic features of tumors can change either following natural tumor progression (i.e., in primary tumors versus metastasis) or therapeutic interventions. In this regard, recent findings by independent teams indicate that antiangiogenic drugs cause metabolic perturbations in tumors as well as metabolic adaptations associated with increased malignancy. Induced metabolic bioluminescence imaging (imBI) is an imaging technique that enables detection of key metabolites associated with glycolysis, including lactate, glucose, pyruvate, and ATP in tumor sections. Signals captured by imBI can be used to visualize the topographic distribution of these metabolites and quantify their absolute amount. imBI can be very useful for metabolic classification of tumors as well as to track metabolic changes in the glycolytic pathway associated with certain therapies. Imaging of the metabolic changes induced by antiangiogenic drugs in tumors by imBI or other emerging technologies is a valuable tool to uncover molecular sensors engaged by metabolic stress and offers an opportunity to understand how metabolism-based approaches could improve cancer therapy. PMID- 26870695 TI - Validation of Claims Algorithms for Progression to Metastatic Cancer in Patients with Breast, Non-small Cell Lung, and Colorectal Cancer. AB - BACKGROUND: Validated algorithms for identifying progression to metastatic cancer could permit the use of administrative claims databases for research in this area. OBJECTIVE: To identify simple algorithms that could accurately detect cancer progression to metastatic breast, non-small cell lung, and colorectal cancer (CRC) using medical and pharmacy claims data. METHODS: Adults with stage I III breast, non-small cell lung cancer (NSCLC), or CRC in the Geisinger Health System from 2004 to 2011 were selected. Evidence of progression was extracted via manual chart review as the reference standard. In addition to secondary malignancy diagnosis (ICD-9 code for metastases), diagnoses, procedures, and treatments were selected with clinician input as indicators of cancer progression. Random forests models provided variable importance scores. In addition to codes for secondary malignancy, several more complex algorithms were constructed and performance measures calculated. RESULTS: Among those with breast cancer [17/502 (3.4%) progressed], the performance of a secondary malignancy code was suboptimal [sensitivity: 64.7%; specificity: 86.0%; positive predictive value (PPV): 13.9; negative predictive value (NPV): 98.6%]; requiring malignancy at another site or initiation of immunotherapy increased PPV and specificity but decreased sensitivity. For NSCLC [61/236 (25.8%) progressed], codes for secondary malignancy alone (PPV: 47.4%; NPV: 84.8%; sensitivity: 60.7%; specificity: 76.6%) performed similarly or better than more complex algorithms. For CRC [33/276 (12.0%) progressed], secondary malignancy codes had good specificity (92.7%) and NPV (92.3%) but low sensitivity (42.4%) and PPV (43.8%); an algorithm with change in chemotherapy increased sensitivity but decreased other metrics. CONCLUSION: Selected algorithms performed similarly to the presence of a secondary tumor diagnosis code, with low sensitivity/PPV and higher specificity/NPV. Accurate identification of cancer progression likely requires verification through chart review. PMID- 26870696 TI - Preventing Cervical Cancer in the United States: Barriers and Resolutions for HPV Vaccination. AB - Human papillomavirus (HPV) vaccination rates for preadolescent and adolescent girls in the United States are far behind those of other developed nations. These rates differ substantially by region and state, socioeconomic status, and insurance status. In parents and young women, a lack of awareness and a misperception of the risk of this vaccine drive low vaccination rates. In physicians, lack of comfort with discussion of sexuality and the perception that the vaccine should be delayed to a later age contribute to low vaccination rates. Patient- and physician-targeted educational campaigns, systems-based interventions, and school-based vaccine clinics offer a variety of ways to address the barriers to HPV vaccination. A diverse and culturally appropriate approach to promoting vaccine uptake has the potential to significantly improve vaccination rates in order to reach the Healthy People 2020 goal of over 80% vaccination in adolescent girls. This article reviews the disparities in HPV vaccination rates in girls in the United States, the influences of patients', physicians', and parents' attitudes on vaccine uptake, and the proposed interventions that may help the United States reach its goal for vaccine coverage. PMID- 26870697 TI - Radiation Metabolomics: Current Status and Future Directions. AB - Human exposure to ionizing radiation (IR) disrupts normal metabolic processes in cells and organs by inducing complex biological responses that interfere with gene and protein expression. Conventional dosimetry, monitoring of prodromal symptoms, and peripheral lymphocyte counts are of limited value as organ- and tissue-specific biomarkers for personnel exposed to radiation, particularly, weeks or months after exposure. Analysis of metabolites generated in known stress responsive pathways by molecular profiling helps to predict the physiological status of an individual in response to environmental or genetic perturbations. Thus, a multi-metabolite profile obtained from a high-resolution mass spectrometry-based metabolomics platform offers potential for identification of robust biomarkers to predict radiation toxicity of organs and tissues resulting from exposures to therapeutic or non-therapeutic IR. Here, we review the status of radiation metabolomics and explore applications as a standalone technology, as well as its integration in systems biology, to facilitate a better understanding of the molecular basis of radiation response. Finally, we draw attention to the identification of specific pathways that can be targeted for the development of therapeutics to alleviate or mitigate harmful effects of radiation exposure. PMID- 26870698 TI - Targeting of Mutant p53 and the Cellular Redox Balance by APR-246 as a Strategy for Efficient Cancer Therapy. AB - TP53 is the most frequently mutated gene in cancer. The p53 protein activates transcription of genes that promote cell cycle arrest or apoptosis, or regulate cell metabolism, and other processes. Missense mutations in TP53 abolish specific DNA binding of p53 and allow evasion of apoptosis and accelerated tumor progression. Mutant p53 often accumulates at high levels in tumor cells. Pharmacological reactivation of mutant p53 has emerged as a promising strategy for improved cancer therapy. Small molecules that restore wild type activity of mutant p53 have been identified using various approaches. One of these molecules, APR-246, is a prodrug that is converted to the Michael acceptor methylene quinuclidinone (MQ) that binds covalently to cysteines in p53, leading to refolding and restoration of wild type p53 function. MQ also targets the cellular redox balance by inhibiting thioredoxin reductase (TrxR1) and depleting glutathione. This dual mechanism of action may account for the striking synergy between APR-246 and platinum compounds. APR-246 is the only mutant p53-targeting compound in clinical development. A phase I/IIa clinical trial in hematological malignancies and prostate cancer showed good safety profile and clinical effects in some patients. APR-246 is currently tested in a phase Ib/II trial in patients with high-grade serous ovarian cancer. PMID- 26870699 TI - Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture. AB - Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS), which is a zoonosis endemic in eastern Asia, especially in China. The reservoir host of HTNV is field mouse (Apodemus agraricus). The main manifestation of HFRS, including acute kidney injury, increases vascular permeability, and coagulation abnormalities. In this paper, we review the current knowledge of the pathogenesis of HFRS including virus factor, immunity factor and host genetic factors. Furthermore, the treatment and prevention will be discussed. PMID- 26870700 TI - Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism. AB - Microsporidia are a group of intracellular pathogens causing self-limited and severe diseases in immunocompetent and immunocompromised individuals, respectively. A cellular type 1 adaptive response, mediated by IL-12, IFNgamma, CD4+, and CD8+ T cells has been shown to be essential for host resistance, and dendritic cells (DC) play a key role at eliciting anti-microsporidial immunity. We investigated the in vitro response of DC and DC precursors/progenitors to infection with Encephalitozoon intestinalis (Ei), a common agent of human microsporidosis. Ei-exposed DC cultures up-regulated the surface expression of MHC class II and the costimulatory molecules CD86 and CD40, only when high loads of spores were used. A vigorous secretion of IL-6 but not of IL-1beta or IL-12p70 was also observed in these cultures. Ei-exposed DC cultures consisted of immature infected and mature bystander DC, as assessed by MHC class II and costimulatory molecules expression, suggesting that intracellular Ei spores deliver inhibitory signals in DC. Moreover, Ei selectively inhibited the secretion of IL-12p70 in LPS-stimulated DC. Whereas Ei-exposed DC promoted allogeneic naive T cell proliferation and IL-2 and IFNgamma secretion in DC-CD4+ T cell co-cultures, separated co-cultures with bystander or infected DCs showed stimulation or inhibition of IFNgamma secretion, respectively. When DC precursors/progenitors were exposed to Ei spores, a significant inhibition of DC differentiation was observed without shifting the development toward cells phenotypically or functionally compatible with myeloid-derived suppressor cells. Neutralization experiments demonstrated that this inhibitory effect is IL-6-dependent. Altogether this investigation reveals a novel potential mechanism of immune escape of microsporidian parasites through the modulation of DC differentiation and maturation. PMID- 26870702 TI - Effect of Abstinence on Audio-Visual Reaction Time in Chronic Smokers Pursuing a Professional Course. AB - INTRODUCTION: It has now been proven that tobacco abuse is the leading cause for various carcinomas such as oral, lung and oesophageal. It also leads to atherosclerosis of major vessels, development of hypertension, autoimmune disorders, COPD, bronchitis, asthma, bronchiectasis, etc. Most smokers are dependent on nicotine and abstinence from smoking results in tobacco withdrawal and craving. It also affects cognitive skills and reaction time. Many students in professional college have the habit of smoking. In spite of awareness programmes carried out in schools, colleges and having ban on smoking, prevalence of smoking is rising in India. AIM: To observe the effect of abstinence on audiovisual reaction time and to note the cause for reverting to smoking by the students pursing professional course. MATERIALS AND METHODS: Sixty male volunteers in the age group of 18-25 years participated in the study. The volunteers were divided in to two groups (control group and study group). Cigarette smokers consuming at least 10-19 cigarettes per day for more than 2-3 years were included as subjects in study group. The study was conducted using a audiovisual reaction time apparatus in a quiet and bright lit room. All volunteers were subjected to baseline readings after demonstrating working of the apparatus. Auditory (high pitched and low pitched sound) and visual (red light and green light) reaction time was recorded. Thirty students in study group were subjected to these tests immediately after smoking and after 12 hours of abstinence. After all the individuals were tested, the recorded values were compared by Student's t-test. RESULTS: Statistically significant difference was recorded in auditory and visual reaction time in study group subjects immediately after smoking and after 12 hours of abstinence as compared to base line readings. CONCLUSION: It was observed that auditory and visual reaction time was prolonged in chronic smokers after 12 hours of abstinence. PMID- 26870701 TI - MicroRNAs in the Host-Apicomplexan Parasites Interactions: A Review of Immunopathological Aspects. AB - MicroRNAs (miRNAs), a class of small non-coding regulatory RNAs, have been detected in a variety of organisms ranging from ancient unicellular eukaryotes to mammals. They have been associated with numerous molecular mechanisms involving developmental, physiological and pathological changes of cells and tissues. Despite the fact that miRNA-silencing mechanisms appear to be absent in some Apicomplexan species, an increasing number of studies have reported a role for miRNAs in host-parasite interactions. Host miRNA expression can change following parasite infection and the consequences can lead, for instance, to parasite clearance. In this context, the immune system signaling appears to have a crucial role. PMID- 26870703 TI - A Prospective Comparative Study of the Toxicity Profile of 5-Flurouracil, Adriamycin, Cyclophosphamide Regime VS Adriamycin, Paclitaxel Regime in Patients with Locally Advanced Breast Carcinoma. AB - INTRODUCTION: A 5-flurouracil, Adriamycin, Cyclophosphamide (FAC) and Adriamycin, Paclitaxel (AT) are two popular chemotherapeutic regimens for treatment of breast carcinoma. The most time tested and popular regimen is FAC. It is extensively studied for efficacy and toxicity. But data regarding toxicity profile and efficacy of AT regimen is sparse. AIM: To study the toxicity profile, severity of toxicities and clinical response rate of FAC and AT regimens in patients with locally advanced breast carcinoma. MATERIALS AND METHODS: A prospective observational study with 50 patients in each treatment arm. Study duration was 12 months from November 2012 to October 2013. Consecutive patients with locally advanced breast carcinoma receiving treatment with either FAC or AT regimen, satisfying inclusion criteria were enrolled into the study after getting informed written consent. Prior to initiation of treatment detailed medical history was taken from all patients. General clinical examination, examination of organ systems and local examination of breast lump were done. After each cycle of chemotherapy and after completion of treatment patients were interviewed and examined for clinical response and toxicities. Toxicities were graded with WHO toxicity grading criteria. All data were entered in a structured proforma. At least 50% reduction in tumour size was taken as adequate clinical response. STATISTICAL ANALYSIS: Data was analysed using Chi-square test with help of Excel 2007 and SPSS-16 statistical software. RESULTS: Different pattern of toxicities were seen with FAC and AT regimens. Anaemia, thrombocytopenia, stomatitis, hyperpigmentation, photosensitivity and diarrhoea were more common with patients receiving FAC regimen. Leucopenia, peripheral neuropathy, myalgia, arthralgia, vomiting and injection site reactions were more common in AT regimen. Both FAC and AT regimens gave 100% clinical response. CONCLUSION: FAC and AT regimens are equally efficacious but have different toxicity profiles. Patient's predisposition to toxicities may govern the selection of a particular regime. PMID- 26870704 TI - Diuretic Activity of Ethanolic Root Extract of Mimosa Pudica in Albino Rats. AB - INTRODUCATION: Diuretics are the drugs which increase the urine output. This property is useful in various pathological conditions of fluid overload. The presently available diuretics have lot of adverse effects. Our study has evaluated the diuretic activity of ethanolic root extract of Mimosa pudica as an alternative/new drug which may induce diuresis. AIM: To evaluate the diuretic activity of ethanolic root extract of Mimosa pudicaa in albino rats. MATERIALS AND METHODS: Ethanolic root extract of Mimosa pudica (EEMP) was prepared using soxhlet's apparatus. Albino rats were divided into 5 groups of 6 rats each. Group I (Control) received distilled water 25ml/kg orally. Group-II (Standard) received Furosemide 20mg/kg orally. Group-III received EEMP 100 mg/kg, Group-IV received EEMP 200 mg/kg and Group-V received EEMP 400 mg/kg. The urine samples were collected for all the groups upto 5 hours after dosing and urine volume was measured. Urine was analysed for electrolytes (Na+, K+ and Cl-). ANOVA, Dunnet's test and p-values were measured and data was analysed. RESULTS: EEMP exhibited significant diuretic activity by increasing urine volume and also by enhancing elimination of Sodium (Na+), Potassium (K+) and Chloride (Cl-) at doses of 100 and 200mg/kg. CONCLUSION: EEMP possesses significant diuretic activity and has a beneficial role in volume overload conditions. PMID- 26870705 TI - Frequency of Anxiety in Patients With Drug Poisoning in Rafsanjan City, Iran, in 2013. AB - BACKGROUND: Expansion of technology and progression of sciences have led to wider access to agricultural and industrial drugs and chemicals, which has resulted in many problems. Both in wanted and unwanted ways people may take these toxic agents, which perhaps may be along with many unpredictable, life-threatening and mortal outcomes. Based on many studies, most of intentional poisonings arise from an origin of patients' psychological backgrounds, which confirms necessity and importance of the recent study. OBJECTIVES: This study aimed to study the prevalence of psychiatric disorders in patients with drug poisoning. PATIENTS AND METHODS: In this descriptive cross-sectional study, 116 cases of poisoning referred to emergency room of Ali-Ebn-Abitaleb Hospital in Rafsanjan city, Iran, were randomly selected. Frequency of anxiety among participants was evaluated through the Spielberger questionnaire. A past history of depression and obsession was also evaluated through interview by a psychiatrist based on diagnostic and statistical manual of mental disorders (DSM-5) criteria. All data were then collected and analyzed using SPSS version 17. RESULTS: Anxiety, as the second most common reason of psychiatric disorders in cases of poisoning, with a prevalence of 12.1% in form of mild, 75.9% moderate and 12.1% severe, was confirmed among the participants of this study. CONCLUSIONS: The prevalence of anxiety among cases of poisoning with both drugs and chemicals are noticeably higher than general population. This fact strongly suggests the necessity of in advance consultation and treatment of any underlying psychiatric disorders of patients to prevent prospective complications. PMID- 26870706 TI - Temperament and Character Dimensions: Correlates of Impulsivity in Morphine Addicts. AB - BACKGROUND: Given the role of temperament and character dimensions on impulsivity in addicts, the purpose of this study was to temperament and character dimensions: correlates of impulsivity in morphine addicts. OBJECTIVES: The aim of this study was to determine and verify the association of temperament and character dimensions with impulsivity in morphine addicts. PATIENTS AND METHODS: The research method was descriptive and correlational. The study sample consisted of 120 morphine addicts referred to drug addiction treatment centers in Ardabil city in 2013. The participants were selected through convenience sampling method from 5 centers. We used impulsivity scale as well as temperament and character inventory to collect data. RESULTS: The results showed that significant relationship existed between impulsivity and characteristics such as novelty seeking, harm avoidance, reward dependence, persistence, self-directedness, and cooperativeness, while no significant relationship between impulsivity and self transcendence was observed. The results of the multiple regression analysis showed that 47% of the impulsivity variance was explained by temperament and character dimensions. CONCLUSIONS: These findings suggest that temperament and character dimensions are associated with impulsivity. The findings also have important implications for prevention, pathology, and treatment in the morphine addicts. PMID- 26870707 TI - Effectiveness of Hope Therapy Protocol on Depression and Hope in Amphetamine Users. AB - BACKGROUND: Addiction has surpassed the boundaries of health and treatment and turned into a social crisis and a debilitating and major concern in today's world. Amphetamine, one of the addictive drugs, is classified as psycho stimulants drugs, which increase arousal, alertness, and motor activity. Humans report that this drug produces a significant euphoria and is highly addictive. OBJECTIVES: The present study aimed to evaluate the effectiveness of hope therapy protocol (HTP) on depression reduction and hope increase in amphetamine users. PATIENTS AND METHODS: This study has a quasi-experimental design with experimental and control groups. The sample included all amphetamine consumers referring to day drug addiction treatment center in Ray City, Iran, selected with convenience method. In order to analyze the data, multivariate analysis of covariance (MANCOVA) was applied using SPSS software. RESULTS: The results showed that F value of mean scores in depression and hope post-tests of the experimental and control groups are 24.94 and 25.73, respectively, which are significant (P < 0.01). Therefore, hope therapy training could reduce depressive symptoms in amphetamine consumers and improve their hope. CONCLUSIONS: Performing HTP can improve hopefulness and symptoms of patients, specially addicted ones. In addition, it can prevent substance abusers from returning to drugs and leaving the treatment period unfinished. PMID- 26870708 TI - Quality of Life in Methadone Maintenance Treated Patients in Iran. AB - BACKGROUND: Measurement of life quality as an index of health status has a widespread application in health care domain. OBJECTIVES: The current study aimed to determine the quality of life of referents to addiction cessation centers of Iran. PATIENTS AND METHODS: In this cross-sectional study, 988 addicts who had referred to addiction cessation centers in Shahroud were studied through SF-36 questionnaire. The data were analyzed using linear regression in structural equation modeling and STATA 12 statistical software. RESULTS: The mean +/- SD age of the participants was 41.2 +/- 11.8 years. Most of the referents used smoking followed by eating method of opium abuse. The mean +/- SD score of life quality was 67.8 +/- 17.2, the mean +/- SD score of life quality in physical health dimension was 76.9 +/- 26.7, and the mean +/- SD score in mental health dimension was 64.5 +/- 18.4. Univariate analysis showed a significant relationship between life quality and gender, place of residence, education, occupation, marital status, and income (P <= 0.05). However, in multivariate analysis a significant relationship was observed only between gender, socioeconomic status, and quality of life score. CONCLUSIONS: Although most studies have reported low and weak quality of life in addicts, the findings of this study shows that the life quality score of addicts is rather good. It seems that the maintenance treatment that addicts receive in addiction cessation centers has been effective in improving the quality of life of the patients. Hence, expanding methadone treatment centers can play a leading role in the improvement of life quality in addicts. PMID- 26870709 TI - Iran's Activities on Prevention, Treatment and Harm Reduction of Drug Abuse. AB - CONTEXT: In the present review study, authors investigated Iran's activities regarding prevention, abuse and harm reduction of drugs nationwide. The issue appears to be important in order to show the trend of activities in the country. EVIDENCE ACQUISITION: In this report, authors gathered data from different Farsi/English peer review journals issued both in printed and online versions. These journals have been indexed in PubMed, ISI, ISC, SID, Magiran, UN, etc. These are among the most referred and cited databases. RESULTS: Summarizing the data led to three distinguished sections: 1) drug supply reduction activities; 2) drug demand reduction activities; 3) harm reduction activities. CONCLUSIONS: As the results showed, the trend of activities was encouraging and some additional activities could be included to future programs relying on early-onset preventions. PMID- 26870710 TI - Sleep Quality and Sexual Function in Patients Under Methadone Maintenance Treatment. AB - BACKGROUND: Methadone maintenance has remained the main modality of treatment for opioid dependent subjects. Side effects of methadone treatment may be potential obstacles to its continuation. Sleep quality and sexual function are two culture based concerns, directly related to patients' compliance with methadone maintenance treatment (MMT) program. OBJECTIVES: This research was conducted to examine the frequency of sleep disparity and sexual dysfunction in patients under MMT referring to MMT clinics of Kerman, Iran. PATIENTS AND METHODS: In this cross sectional study, 198 adult subjects under MMT for more than 6 months were enrolled. Measurement tool consisted of Pittsburgh sleep quality index (PSQI), Arizona sexual experience scale (ASEX), the 12-item general health questionnaire (GHQ-12), and a demographic questionnaire. The questionnaires were self completed, except where individuals were illiterate. RESULTS: Mean +/- SD age of the subjects was 41.2 +/- 7.9 years and 93.4% of them were male. More than half of them used heroin. Prevalence of poor sleeping and sexual dysfunction in patients under MMT were 67.7% and 18.2%, respectively. There was no association between sleep quality or sexual dysfunction and demographics or methadone dose. However, a significant correlation was observed between mental health and sleep quality (r =0.16, P = 0.033), and sexual function (r = 0.18, P = 0.011). CONCLUSIONS: Sleep quality showed a poorer profile than sexual function. Therefore, more emphasis should be laid on treatment of sleep disparity during follow up of MMT patients comparing to their sexual function. Patients should be reassured that probable sexual dysfunctions should not be regarded as a consequence of MMT. PMID- 26870711 TI - Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Risk (HIV/AIDS) Taking Behavior and HIV/AIDS Knowledge With African-American Women. PMID- 26870712 TI - Role of Temperament, Personality Traits and Onset Age of Smoking in Predicting Opiate Dependence. AB - BACKGROUND: According to drug gateway theory, smoking cigarettes, especially, low onset age of smoking, is one of the risk factors for future use. OBJECTIVES: The present study aimed to compare nicotine and opiate addicts to identify the differences in personality traits and onset age of smoking in the two groups that cause some individuals to appeal to other substances after starting to use cigarettes. PATIENTS AND METHODS: Two groups of opiate and nicotine addicts were randomly selected. Revised version of the Cloninger temperament inventory questionnaire, the Fagrastrom nicotine dependence and the Maudsley addiction profile were used. ANOVA and logistic regression were applied for data analysis. RESULTS: Opiate addicts had higher scores in novelty seeking dimension and lower scores in cooperativeness compared to nicotine addicts. The onset age of smoking cigarette in opiate addicts was lower than nicotine addicts. CONCLUSIONS: Low onset age of smoking cigarettes, high novelty seeking and low cooperativeness in opiate dependents are among the important personality traits in future use of drugs that can predict the subsequent onset of using opiate drugs. PMID- 26870714 TI - Internet Gaming Addiction: A Technological Hazard. AB - INTRODUCTION: The Internet is considered a beneficial tool in research, communication, and information. Still, its excessive and prolonged use has the potential of causing addiction. The presentation of this technological hazard may range from a mild socio-personal distress to a gross disorganization in behavior and self-care. No reported study on Internet gaming addiction is available from India. CASE PRESENTATION: We reported a case of two brothers, diagnosed with Internet gaming addiction, who showed grossly disorganized behavior and severely compromised self-care. The condition was managed by pharmacological and non pharmacological therapies, with sustained improvement after 6 months follow up. CONCLUSIONS: Internet gaming addiction may cause severe personal, social, and occupational problems. Despite the range of severity and various presentations of this disorder, DSM-5 lacks the severity classifier. Early identification and management may result in complete recovery. PMID- 26870713 TI - Developing a Brief Scale to Measure HIV Transmission Risk Among Injecting Drug Users. AB - BACKGROUND: One of the main concerns of policymakers is to measure the impact of harm reduction programs and different interventions on the risk of HIV transmission among Injecting Drug Users (IDUs). Looking simultaneously at multiple factors and conditions that affect the risk of HIV transmission may provide policymakers a better insight into the mixed nature of HIV transmission. OBJECTIVES: The present study aimed to design a simple, brief, and multi dimensional scale for measuring HIV transmission risk among IDUs. PATIENTS AND METHODS: From October 2013 to March 2014, we conducted face-to-face interviews with 147 IDUs. Eligible participants were individuals 18 years or older who had injected drugs at least once during the last year and had not participated in similar studies within the 2 months before the interview. To design a scale for measuring HIV transmission risk, we specified 11 items, which address different dimensions of HIV risk taking behaviors/situations based on experts' opinion. We applied exploratory factor analysis (EFA) with principal component extraction to develop scales. Eigen values greater than 1 were used as a criterion for factor extraction. RESULTS: We extracted 7 items based on first factor, which were accounted for 21% of the variations. The final scale contained 7 items: 4 items were related to injecting practice and 3 items related to sexual behaviors. The Cronbach's alpha coefficient was 0.66, acceptable for such a brief scale. CONCLUSIONS: Applying a simple and brief scale that incorporates the different dimensions of HIV transmission risk may provide policymakers and harm reductionists with a better understanding of HIV transmission in this key group and may be advantageous for evaluating intervention programs. PMID- 26870715 TI - Galectin-3 Serum Levels Are Independently Associated With Microalbuminuria in Chronic Heart Failure Outpatients. AB - BACKGROUND: Galectin-3 (Gal-3) is a novel biomarker reflecting inflammation status and fibrosis involving worsening of both cardiac and renal functions. OBJECTIVES: The aim of this study was to evaluate the relationship between Gal-3 serum levels and microalbuminuria in a group of chronic heart failure (CHF) outpatients. PATIENTS AND METHODS: We enrolled CHF outpatients having stable clinical conditions and receiving conventional therapy. All patients underwent clinical evaluation, routine chemistry analysis, echocardiography, and evaluation of the urinary albumin/creatinine ratio (UACR). RESULTS: Among the patients enrolled, 61 had microalbuminuria (UACR, 30-299) and 133 normoalbuminuria (UACR, < 30). Patients with normoalbuminuria showed significantly higher levels of Gal-3 than those without (19.9 +/- 8.8 vs. 14.6 +/- 5.5 ng/mL). The stepwise regression analysis indicated that Gal-3 was the first determinant of microalbuminuria (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02 - 1.14, P = 0.012), followed by diabetes (OR 2.14; 95% CI: 1.00 - 4.57; P = 0.049) and high central venous pressure (OR 2.80; 95% CI: 1.04 - 7.58; P= 0.042). CONCLUSIONS: Our findings indicate an independent association between Gal-3 levels and microalbuminuria, an early marker of altered renal function. This suggests the possible role of Gal-3 in the progression of cardiorenal syndrome in CHF outpatients. PMID- 26870716 TI - Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer. AB - A splice variant of androgen receptor (AR), AR-V7, lacks in androgen-binding portion and leads to aggressive cancer characteristics. Reverse transcription polymerase chain reactions (PCRs) and subsequent nested PCRs for the amplification of AR-V7 and prostate-specific antigen (PSA) transcripts were done for whole blood of patients with prostate cancer and male controls. With primary reverse transcription PCRs, AR-V7 and PSA were detected in 4.5% and 4.7% of prostate cancer, respectively. With nested PCRs, AR-V7 messenger RNA (mRNA) was positive in 43.8% of castration-sensitive prostate cancer and 48.1% of castration resistant prostate cancer (CRPC), while PSA mRNA was positive in 6.3% of castration-sensitive prostate cancer and 18.5% of CRPC. Whole-blood samples of controls showed AR-V7 mRNA expression by nested PCR. Based on multivariate analysis, expression of AR-V7 mRNA in whole blood was not significantly correlated with clinical parameters and PSA mRNA in blood, while univariate analysis showed a correlation between AR-V7 mRNA and metastasis at initial diagnosis. Detection of AR-V7 mRNA did not predict the reduction of serum PSA in patients with CRPC following abiraterone and enzalutamide administration. In conclusion, AR-V7 mRNA expression in normal hematopoietic cells may have annihilated the manifestation of aggressiveness of prostate cancer and the prediction of the effectiveness of abiraterone and enzalutamide by the assessment of AR-V7 mRNA in blood. PMID- 26870717 TI - Bisphosphonate-related osteonecrosis of the jaw in metastatic breast cancer patients: a review of 25 cases. AB - BACKGROUND: Intravenous bisphosphonates have been used in metastatic breast cancer patients to reduce pathologic bone fracture and bone pain. However, necrosis of the jaw has been reported in those who received intravenous bisphosphonates. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is caused by dental extraction, dental implant surgery, and denture wearing; however, it occurs spontaneously. The purpose of this study was to report BRONJ in metastatic breast cancer patients. METHODS: Consecutive 25 female patients were referred from the Department of Oncology from 2008 to 2014 for jaw bone discomfort. Staging of breast cancer, history of bisphosphonate infusion, etiology of BRONJ, and treatment results were reviewed. Average age of the patients was 55.4 years old (38-74). Twelve maxillae and 16 mandibles were involved. Conservative treatments such as irrigation, antibiotic medication, analgesics, and oral gargle were applied for all patients for the initial treatment. Patients who had sequestrum underwent debridement and primary closure. RESULTS: The etiologies of BRONJ were dental extraction (19 cases), dental implant (2 cases), and endodontic treatment (1 case). However, three patients did not have any risk factors to cause BRONJ. Three patients died of progression of metastasis during follow-up periods. Surgical debridement was performed in 21 patients with success in 18 patients. Three patients showed recurred bone exposure and infection after operation. CONCLUSIONS: Prevention of the BRONJ is critical in metastatic breast cancer patients. Conservative treatment to reduce pain, discomfort, and infection is recommended for the initial therapy. However, if there is a sequestrum, surgical debridement and primary closure is the key to treat the BRONJ. PMID- 26870718 TI - Editorial: Current Challenges in Immune and Other Acquired Cytopenias of Childhood. PMID- 26870719 TI - Dietary Prebiotics, Milk Fat Globule Membrane, and Lactoferrin Affects Structural Neurodevelopment in the Young Piglet. AB - INTRODUCTION: Milk fat globule membrane (MFGM) and lactoferrin have been identified as two components that have potential to affect neurodevelopment. While concentrations of some MFGM constituents in infant formulas are within human milk range, they may not be present at optimal or clinically effective levels. However, lactoferrin levels of infant formulas are consistently reported to be lower than human milk. This study sought to provide a novel combination of prebiotics, bovine-derived MFGM, and lactoferrin and assess their influence on neurodevelopment. METHODS: Twenty-four male piglets were provided either TEST (n = 12) or CONT (n = 12) diet from 2 to 31 days of age. Piglets underwent spatial T maze assessment starting at 17 days of age, were subjected to magnetic resonance imaging at 30 days of age, and were euthanized for tissue collection at 31 days of age. RESULTS: Diffusion tensor imaging revealed differences in radial (P = 0.032) and mean (P = 0.028) diffusivities in the internal capsule, where CONT piglets had higher rates of diffusion compared with TEST piglets. Voxel-based morphometry indicated larger (P < 0.05) differences in cortical gray and white matter concentrations, with CONT piglets having larger tissue clusters in these regions compared with TEST piglets. In the spatial T-maze assessment, CONT piglets exhibited shorter latency to choice compared with TEST piglets on day 2 of acquisition and days 3 and 4 of reversal. CONCLUSION: Observed differences in microstructure maturation of the internal capsule and cortical tissue concentrations suggest that piglets provided TEST diet were more advanced developmentally than piglets provided CONT diet. Therefore, supplementation of infant formula with prebiotics, MFGM, and lactoferrin may support neurodevelopment in human infants. PMID- 26870720 TI - Experience with Quality Assurance in Two Store-and-Forward Telemedicine Networks. AB - Despite the increasing use of telemedicine around the world, little has been done to incorporate quality assurance (QA) into these operations. The purpose of the present study was to examine the feasibility of QA in store-and-forward teleconsulting using a previously published framework. During a 2-year study period, we examined the feasibility of using QA tools in two mature telemedicine networks [Medecins Sans Frontieres (MSF) and New Zealand Teledermatology (NZT)]. The tools included performance reporting to assess trends, automated follow-up of patients to obtain outcomes data, automated surveying of referrers to obtain user feedback, and retrospective assessment of randomly selected cases to assess quality. In addition, the senior case coordinators in each network were responsible for identifying potential adverse events from email reports received from users. During the study period, there were 149 responses to the patient follow-up questions relating to the 1241 MSF cases (i.e., 12% of cases), and there were 271 responses to the follow-up questions relating to the 639 NZT cases (i.e., 42% of cases). The collection of user feedback reports was combined with the collection of patient follow-up data, thus producing the same response rates. The outcomes data suggested that the telemedicine advice proved useful for the referring doctor in the majority of cases and was likely to benefit the patient. The user feedback was overwhelmingly positive, over 90% of referrers in the two networks finding the advice received to be of educational benefit. The feedback also suggested that the teleconsultation had provided cost savings in about 20% of cases, either to the patient/family, or to the hospital/clinic treating the patient. Various problems were detected by regular monitoring, and certain adverse events were identified from email reports by the users. A single aberrant quality reading was detected by using a process control chart. The present study demonstrates that a QA program is feasible in store-and-forward telemedicine, and shows that it was useful in two different networks, because certain problems were detected (and then solved) that would not have been identified until much later. It seems likely that QA could be used much more widely in telemedicine generally to benefit patient care. PMID- 26870721 TI - Corrigendum: Examining the Correlation between Objective Injury Parameters, Personality Traits and Adjustment Measures among Burn Victims. AB - [This corrects the article on p. 49 in vol. 3, PMID: 25874193.]. PMID- 26870723 TI - Employing the Precautionary Principle to Evaluate the Use of E-Cigarettes. AB - Electronic cigarettes (e-cigarettes) have emerged onto the public market as an alternative to tobacco cigarettes; however, science is inconclusive as e cigarettes have not been thoroughly investigated, including their short- and long term risks and benefits (1, 2). The question arises of whether e-cigarettes will become the future tobacco crisis. This paper connects the precautionary principle to the use of e-cigarettes in an effort to guide decision-makers in the prevention of adverse health outcomes and societal costs. PMID- 26870722 TI - Biosurveillance in Central Asia: Successes and Challenges of Tick-Borne Disease Research in Kazakhstan and Kyrgyzstan. AB - Central Asia is a vast geographic region that includes five former Soviet Union republics: Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan. The region has a unique infectious disease burden, and a history that includes Silk Road trade routes and networks that were part of the anti-plague and biowarfare programs in the former Soviet Union. Post-Soviet Union biosurveillance research in this unique area of the world has met with several challenges, including lack of funding and resources to independently conduct hypothesis driven, peer-review quality research. Strides have been made, however, to increase scientific engagement and capability. Kazakhstan and Kyrgyzstan are examples of countries where biosurveillance research has been successfully conducted, particularly with respect to especially dangerous pathogens. In this review, we describe in detail the successes, challenges, and opportunities of conducting biosurveillance in Central Asia as exemplified by our recent research activities on ticks and tick borne diseases in Kazakhstan and Kyrgyzstan. PMID- 26870724 TI - Asthma 101 for Schools: Successes and Challenges in Transitioning to Online Delivery. AB - Florida Asthma Program staff worked with evaluators from the Florida State University College of Medicine to assess participation and quality of the American Lung Association's Asthma 101 asthma management education program for school faculty and staff between 2011 and 2014. This included transitioning the program to an online training format for the 2013-2014 school year. Asthma 101 helps school personnel master the basics of asthma physiology and management, with content tailored specifically for elementary and secondary educational settings. The program is assessed with questionnaires at multiple timepoints, yielding a quasi-experimental evaluation design. Evaluators reviewed quantitative data from pretests and qualitative and quantitative data from post-program satisfaction questionnaires. Program spreadsheets listing the dates for delivery and number of attendees were also reviewed. Overall, evaluation findings were positive. In the 2011-2012 program year, 16 different course sessions were offered, and more than half of enrolled participants came from Title I schools. A total of 228 people were trained. In the 2012-2013 program year, 19 different course sessions were offered. Enrollment totals (638) and matching pre- and posttest totals (562) soundly exceeded the target metric of 425. At least 170 (27%) of a total of 638 participants could be verified as coming from the target demographic of Title I school faculty and staff. In the 2013-2014 program year, the course was offered online on a rolling basis via the Florida TRAIN course management system. Enrollment remained high and learner outcomes remained consistently strong across all content areas for knowledge and satisfaction. A total of 406 people participated in the training; complete pre- and posttest data were available for 341 of these individuals; and satisfaction data were available for 325. Of the 406 trainees, 199 (49%) reported working for Title I schools. Evaluation yielded very positive results. An overwhelming majority of participants reported finding the course consistently strong across the board and highly impactful for their own ability to help students manage their asthma effectively. Most participants also reported that they would change/improve their asthma management behaviors in the workplace. Recommendations were developed to help expand future program reach. PMID- 26870726 TI - Experiences in Engaging the Public on Biotechnology Advances and Regulation. AB - Public input is often sought as part of the biosafety decision-making process. Information and communication about the advances in biotechnology are part of the first step to engagement. This step often relies on the developers and introducers of the particular innovation, for example, an industry-funded website has hosted various authorities to respond to questions from the public. Alternative approaches to providing information have evolved, as demonstrated in sub-Saharan Africa where non-governmental organizations and associations play this role in some countries and subregions. Often times, those in the public who choose to participate in engagement opportunities have opinions about the overall biosafety decision process. Case-by-case decisions are made within defined regulatory frameworks, however, and in general, regulatory consultation does not provide the opportunity for input to the overall decision-making process. The various objectives on both sides of engagement can make the experience challenging; there are no clear metrics for success. The situation is challenging because public input occurs within the context of the local legislative framework, regulatory requirements, and the peculiarities of the fairly recent biosafety frameworks, as well as of public opinion and individual values. Public engagement may be conducted voluntarily, or may be driven by legislation. What can be taken into account by the decision makers, and therefore what will be gathered and the timing of consultation, also may be legally defined. Several practical experiences suggest practices for effective engagement within the confines of regulatory mandates: (1) utilizing a range of resources to facilitate public education and opportunities for understanding complex technologies; (2) defining in advance the goal of seeking input; (3) identifying and communicating with the critical public groups from which input is needed; (4) using a clearly defined approach to gathering and assessing what will be used in making the biosafety decision; and (5) communicating using clear and simple language. These practices create a foundation for systematic methods to gather, acknowledge, respond to, and even incorporate public input. Applying such best practices will increase transparency and optimize the value of input from the public. PMID- 26870727 TI - Editorial: Cyanobacteria: The Green E. coli. PMID- 26870725 TI - Detecting Aquaporin Function and Regulation. AB - Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery. PMID- 26870728 TI - A Comparative Data-Based Modeling Study on Respiratory CO2 Gas Exchange during Mechanical Ventilation. AB - The goal of this study is to derive a minimally complex but credible model of respiratory CO2 gas exchange that may be used in systematic design and pilot testing of closed-loop end-tidal CO2 controllers in mechanical ventilation. We first derived a candidate model that captures the essential mechanisms involved in the respiratory CO2 gas exchange process. Then, we simplified the candidate model to derive two lower-order candidate models. We compared these candidate models for predictive capability and reliability using experimental data collected from 25 pediatric subjects undergoing dynamically varying mechanical ventilation during surgical procedures. A two-compartment model equipped with transport delay to account for CO2 delivery between the lungs and the tissues showed modest but statistically significant improvement in predictive capability over the same model without transport delay. Aggregating the lungs and the tissues into a single compartment further degraded the predictive fidelity of the model. In addition, the model equipped with transport delay demonstrated superior reliability to the one without transport delay. Further, the respiratory parameters derived from the model equipped with transport delay, but not the one without transport delay, were physiologically plausible. The results suggest that gas transport between the lungs and the tissues must be taken into account to accurately reproduce the respiratory CO2 gas exchange process under conditions of wide-ranging and dynamically varying mechanical ventilation conditions. PMID- 26870729 TI - Spatio-Temporal Detection of the Thiomonas Population and the Thiomonas Arsenite Oxidase Involved in Natural Arsenite Attenuation Processes in the Carnoules Acid Mine Drainage. AB - The acid mine drainage (AMD) impacted creek of the Carnoules mine (Southern France) is characterized by acid waters with a high heavy metal content. The microbial community inhabiting this AMD was extensively studied using isolation, metagenomic and metaproteomic methods, and the results showed that a natural arsenic (and iron) attenuation process involving the arsenite oxidase activity of several Thiomonas strains occurs at this site. A sensitive quantitative Selected Reaction Monitoring (SRM)-based proteomic approach was developed for detecting and quantifying the two subunits of the arsenite oxidase and RpoA of two different Thiomonas groups. Using this approach combined with FISH and pyrosequencing-based 16S rRNA gene sequence analysis, it was established here for the first time that these Thiomonas strains are ubiquitously present in minor proportions in this AMD and that they express the key enzymes involved in natural remediation processes at various locations and time points. In addition to these findings, this study also confirms that targeted proteomics applied at the community level can be used to detect weakly abundant proteins in situ. PMID- 26870730 TI - Tolerance to Excess-Boron Conditions Acquired by Stabilization of a BOR1 Variant with Weak Polarity in Arabidopsis. AB - Boron (B) is a metalloid that is essential for plant growth but is toxic when present in excess. Arabidopsis BOR1 is a borate exporter, facilitating B translocation from root to shoot under limited-B conditions. BOR1 shows stele side polar localization in the plasma membrane of various root cells, presumably to support B translocation toward the stele. BOR1 is degraded under high-B supply through vacuolar sorting via ubiquitination at the K590 residue to prevent the accumulation of B to a toxic level in shoots. A previous study showed that overexpression of BOR1 under control of the cauliflower mosaic virus 35S RNA promoter improved the growth of Arabidopsis under limited-B conditions without affecting the growth under sufficient-to-excess-B conditions. In this study, we unexpectedly found that ubiquitous expression of a stabilized BOR1 variant improved tolerance to excess-B in Arabidopsis. We established transgenic plants expressing BOR1-GFP fused with hygromycin phosphotransferase (HPT) and BOR1(K590A)-GFP-HPT under control of the ubiquitin 10 promoter. BOR1-GFP-HPT and BOR1(K590A)-GFP-HPT were expressed in various cell types in leaves and roots and showed weak polar localization in root tip cells. BOR1-GFP-HPT, but not BOR1(K590A)-GFP-HPT, was degraded through an endocytic pathway under high-B conditions. Transgenic plants with the stabilized variant BOR1(K590A)-GFP-HPT showed improved root and shoot growth under excess-B conditions. The concentration of B was greater in the shoots of plants with BOR1(K590A)-GFP-HPT or BOR1-GFP-HPT than in those of untransformed wild-type plants. These results suggest that BOR1(K590A)-GFP-HPT confers tolerance to excess-B by excluding B from the cytosol of shoot cells. Results from this study indicate the potential for engineering the trafficking properties of a transporter to produce plants that are tolerant to mineral stress. PMID- 26870731 TI - Virtual Nuclear Envelope Breakdown and Its Regulators in Fission Yeast Meiosis. AB - Ran, a small GTPase, is required for the spindle formation and nuclear envelope (NE) formation. After NE breakdown (NEBD) during mitosis in metazoan cells, the Ran-GTP gradient across the NE is lost and Ran-GTP becomes concentrated around chromatin, thus affecting the stability of microtubules and promoting the assembly of spindle microtubules and segregation of chromosomes. Mitosis in which chromosomes are segregated subsequent to NEBD is called "open mitosis." In contrast, many fungi undergo a process termed "closed mitosis" in which chromosome segregation and spindle formation occur without NEBD. Although the fission yeast Schizosaccharomyces pombe undergoes a closed mitosis, it exhibits a short period during meiosis (anaphase of the second meiosis; called "anaphase II") when nuclear and cytoplasmic proteins are mixed in the presence of intact NE and nuclear pore complexes (NPC). This "virtual" nuclear envelope breakdown (vNEBD) involves changes in the localization of RanGAP1, an activator of Ran-GTP hydrolysis. Recently, Nup132, a component of the structural core Nup107-160 subcomplex of the NPC, has been shown to be involved in the maintenance of the nuclear cytoplasmic barrier in yeast meiosis. In this review, we highlight the possible roles of RanGAP1 and Nup132 in vNEBD and discuss the biological significance of vNEBD in S. pombe meiosis. PMID- 26870732 TI - High Light Intensity Leads to Increased Peroxule-Mitochondria Interactions in Plants. AB - Peroxules are thin protrusions from spherical peroxisomes produced under low levels of reactive oxygen species (ROS) stress. Whereas, stress mitigation favors peroxule retraction, prolongation of the ROS stress leads to the elongation of the peroxisome into a tubular form. Subsequently, the elongated form becomes constricted through the binding of proteins such as dynamin related proteins 3A and 3B and eventually undergoes fission to increase the peroxisomal population within a cell. The events that occur in the short time window between peroxule initiation and the tubulation of the entire peroxisome have not been observed in living plant cells. Here, using fluorescent protein aided live-imaging, we show that peroxules are formed after only 4 min of high light (HL) irradiation during which there is a perceptible increase in the cytosolic levels of hydrogen peroxide. Using a stable, double transgenic line of Arabidopsis thaliana expressing a peroxisome targeted YFP and a mitochondrial targeted GFP probe, we observed sustained interactions between peroxules and small, spherical mitochondria. Further, it was observed that the frequency of HL-induced interactions between peroxules and mitochondria increased in the Arabidopsis anisotropy1 mutant that has reduced cell wall crystallinity and where we show accumulation of higher H2O2 levels than wild type plants. Our observations suggest a testable model whereby peroxules act as interaction platforms for ROS distressed mitochondria that may release membrane proteins and fission factors. These proteins might thus become easily available to peroxisomes and facilitate their proliferation for enhancing the ROS-combating capability of a plant cell. PMID- 26870733 TI - The Effect of a Combination Treatment Using Palonosetron, Promethazine, and Dexamethasone on the Prophylaxis of Postoperative Nausea and Vomiting and QTc Interval Duration in Patients Undergoing Craniotomy under General Anesthesia: A Pilot Study. AB - INTRODUCTION: Postoperative nausea and vomiting (PONV) is a displeasing experience that distresses surgical patients during the first 24 h after a surgical procedure. The incidence of postoperative nausea occurs in about 50%, the incidence of postoperative vomiting is about 30%, and in high-risk patients, the PONV rate could be as high as 80%. Therefore, the study design of this single arm, non-randomized, pilot study assessed the efficacy and safety profile of a triple therapy combination with palonosetron, dexamethasone, and promethazine to prevent PONV in patients undergoing craniotomies under general anesthesia. METHODS: The research protocol was approved by the institutional review board and 40 subjects were provided written informed consent. At induction of anesthesia, a triple therapy of palonosetron 0.075 mg IV, dexamethasone 10 mg IV, and promethazine 25 mg IV was given as PONV prophylaxis. After surgery, subjects were transferred to the surgical intensive care unit or post anesthesia care unit as clinically indicated. Ondansetron 4 mg IV was administered as primary rescue medication to subjects with PONV symptoms. PONV was assessed and collected every 24 h for 5 days via direct interview and/or medical charts review. RESULTS: The overall incidence of PONV during the first 24 h after surgery was 30% (n = 12). The incidence of nausea and emesis 24 h after surgery was 30% (n = 12) and 7.5% (n = 3), respectively. The mean time to first emetic episode, first rescue, and first significant nausea was 31.3 (+/-33.6), 15.1 (+/-25.8), and 21.1 (+/-25.4) hours, respectively. The overall incidence of nausea and vomiting after 24-120 h period after surgery was 30% (n = 12). The percentage of subjects without emesis episodes over 24-120 h postoperatively was 70% (n = 28). No subjects presented a prolonged QTc interval >=500 ms before and/or after surgery. CONCLUSION: Our data demonstrated that this triple therapy regimen may be an adequate alternative regimen for the treatment of PONV in patients undergoing neurological surgery under general anesthesia. More studies with a control group should be performed to demonstrate the efficacy of this regimen and that palonosetron is a low risk for QTc prolongation. CLINICALTRIALSGOV IDENTIFIER: NCT02635828 (https://clinicaltrials.gov/show/NCT02635828). PMID- 26870734 TI - Pathophysiological Factors in the Relationship between Chronological Age and Calculated Lung Age as Detected in a Screening Setting in Community-Dwelling Subjects. AB - AIM: To explore the relationship between pathophysiological factors and premature lung aging in a cohort of community-dwelling subjects in a health-screening setting. METHODS: 16,107 pharmacy customers in Germany (5954 males, 10,153 females; mean age 59.7 years) participated in a lung function screening project by providing demographic data, including smoking status and known airway conditions and performing spirometry with a Vitalograph, a spirometry screening device. Lung age was calculated from the spirometric findings, and the difference between chronological age and calculated lung age was analyzed in its relationship to the demographic data in general linear models. RESULTS: In the overall cohort, calculated lung age exceeded chronological age by 10.0 years. Based on the subset of non-smokers not reporting any airway conditions, Vitalograph data in this setting may underestimate FEV1 to some degree, but this apparently had little impact on the detection of association of lung age with pathophysiological factors or the corresponding effect sizes. The most important factors associated with greater lung age based on strength of association were presence of dyspnea, being a smoker, and reporting a history of COPD or asthma. Corresponding effect sizes for the difference between age and lung age were 6.5, 5.7, 13.9, and 8.3 years over the chronological age. DISCUSSION AND CONCLUSION: These data confirm the usefulness of screening devices of lung function testing for epidemiological but potentially also for pharmaco-epidemiological studies. PMID- 26870736 TI - Multifunctional Gold-Mesoporous Silica Nanocomposites for Enhanced Two-Photon Imaging and Therapy of Cancer Cells. AB - Three dimensional sub-micron resolution has made two-photon nanomedicine a very promising medical tool for cancer treatment since current techniques cause significant side effects for lack of spatial selectivity. Two-photon-excited (TPE) photodynamic therapy (PDT) has been achieved via mesoporous nanoscaffolds, but the efficiency of the treatment could still be improved. Herein, we demonstrate the enhancement of the treatment efficiency via gold-mesoporous organosilica nanocomposites for TPE-PDT in cancer cells when compared to mesoporous organosilica particles. We performed the first comparative study of the influence of the shape and spatial position of gold nanoparticles (AuNPs) with mesoporous silica nanoparticles (MSN) functionalized with thiol groups and doped with a two-photon electron donor (2PS). The resulting multifunctional nanocarriers displayed TPE-fluorescence and were imaged inside cells. Furthermore, mesoporous organosilica NPs decorated gold nanospheres (AuNSs) induced 63 percent of selective killing on MCF-7 breast cancer cells. This study thus provides insights for the design of more effective multifunctional two photon-sensitive nanocomposites via AuNPs for biomedical applications. PMID- 26870735 TI - Effect of Housing Types on Growth, Feeding, Physical Activity, and Anxiety-Like Behavior in Male Sprague-Dawley Rats. AB - BACKGROUND: Animal welfare and accurate data collection are equally important in rodent research. Housing influences study outcomes and can challenge studies that monitor feeding, so housing choice needs to be evidence-based. The goal of these studies was to (1) compare established measures of well-being between rodents housed in wire grid-bottom floors with a resting platform compared to solid bottom floors with bedding and (2) determine whether presence of a chewable device (Nylabone) affects orexin-A-induced hyperphagia. METHODS: Rodents were crossed over to the alternate housing twice after 2-week periods. Time required to complete food intake measurements was recorded as an indicator of feasibility. Food intake stimulated by orexin-A was compared with and without the Nylabone. Blood corticosterone and hypothalamic BDNF were assessed. RESULTS: Housing had no effect on growth, energy expenditure, corticosterone, hypothalamic BDNF, behavior, and anxiety measures. Food intake was disrupted after housing cross over. Time required to complete food intake measurements was significantly higher for solid-bottom bedded cages. The Nylabone had no effect on orexin-A-stimulated feeding. CONCLUSION: Well-being is not significantly different between rodents housed on grid-bottom floors and those in solid-bottom-bedded cages based on overall growth and feeding but alternating between housing confounds measures of feeding. PMID- 26870737 TI - Commentary: Heart Fat Infiltration in Subjects With and Without Coronary Artery Disease. PMID- 26870738 TI - Spatial and Functional Organization of Pig Trade in Different European Production Systems: Implications for Disease Prevention and Control. AB - Understanding the complexity of live pig trade organization is a key factor to predict and control major infectious diseases, such as classical swine fever (CSF) or African swine fever (ASF). Whereas the organization of pig trade has been described in several European countries with indoor commercial production systems, little information is available on this organization in other systems, such as outdoor or small-scale systems. The objective of this study was to describe and compare the spatial and functional organization of live pig trade in different European countries and different production systems. Data on premise characteristics and pig movements between premises were collected during 2011 from Bulgaria, France, Italy, and Spain, which swine industry is representative of most of the production systems in Europe (i.e., commercial vs. small-scale and outdoor vs. indoor). Trade communities were identified in each country using the Walktrap algorithm. Several descriptive and network metrics were generated at country and community levels. Pig trade organization showed heterogeneous spatial and functional organization. Trade communities mostly composed of indoor commercial premises were identified in western France, northern Italy, northern Spain, and north-western Bulgaria. They covered large distances, overlapped in space, demonstrated both scale-free and small-world properties, with a role of trade operators and multipliers as key premises. Trade communities involving outdoor commercial premises were identified in western Spain, south-western and central France. They were more spatially clustered, demonstrated scale-free properties, with multipliers as key premises. Small-scale communities involved the majority of premises in Bulgaria and in central and Southern Italy. They were spatially clustered and had scale-free properties, with key premises usually being commercial production premises. These results indicate that a disease might spread very differently according to the production system and that key premises could be targeted to more cost-effectively control diseases. This study provides useful epidemiological information and parameters that could be used to design risk-based surveillance strategies or to more accurately model the risk of introduction or spread of devastating swine diseases, such as ASF, CSF, or foot and-mouth disease. PMID- 26870739 TI - Practices and Perceptions of Animal Contact and Associated Health Outcomes in Pregnant Women and New Mothers. AB - Companion animals play an important role in our society. However, pregnant women and new mothers might have specific concerns about animal-associated health outcomes because of their altered immune function and posture as well as their newborn babies. The study was conducted to collect baseline data for developing an evidence-based intervention for pregnant women and new mothers to help them adopt certain behaviors to prevent adverse animal-associated health outcomes. A survey, using the Health Belief Model as the theoretical framework, was developed and administered to 326 women attending the Women, Infants, and Children programs in Illinois and Indiana in 2015. Prevalence of dog and cat ownership was estimated to be 39% (95% CI: 33-45%) and 26% (95% CI: 21-31%), respectively. Regardless of pet ownership, 74% of the respondents reported having some type of animal contact in the past month. Pregnancy or the birth of a child altered some animal contact practices among the study participants; particularly a discontinuation or decrease in cleaning cat litter boxes. Reports of diseases contracted from animals were low (4%) in this study. By contrast, animal associated injuries were prevalent (42%), and the majority were caused by animals the respondents owned (56%). Overall, respondents indicated that they appreciated the benefits of a program addressing animal-associated health outcomes and did not indicate strong resistance to adopt certain behaviors. The majority recognized human health-care providers as a source of information about animal contact and associated health outcomes but less frequently identified veterinarians as a source for such information. In addition, although most of the respondents felt that health-care providers and veterinarians should initiate discussions about preventing animal-associated illness and injuries, only 41% among those who had visited doctors or prenatal care services reported that their health-care providers discussed these issues with them. The results indicate the importance of an intervention concerning animal contact and associated health outcomes for the target population and provide insights to the potential implications of program implementation. PMID- 26870740 TI - Simulation of Spread of African Swine Fever, Including the Effects of Residues from Dead Animals. AB - To study the spread of African swine fever (ASF) within a pig unit and the impact of unit size on ASF spread, a simulation model was created. In the model, an animal can be in one of the following stages: susceptible, latent, subclinical, clinical, or recovered. Animals can be infectious during the subclinical stage and are fully infectious during the clinical stage. ASF virus (ASFV) infection through residues of dead animals in the slurries was also modeled in an exponentially fading-out pattern. Low and high transmission rates for ASFV were tested in the model. Robustness analysis was carried out in order to study the impact of uncertain parameters on model predictions. The results showed that the disease may fade out within the pig unit without a major outbreak. Furthermore, they showed that spread of ASFV is dependent on the infectiousness of subclinical animals and the residues of dead animals, the transmission rate of the virus, and importantly the unit size. Moreover, increasing the duration of the latent or the subclinical stages resulted in longer time to disease fade out. The proposed model is a simple and robust tool simulating the spread of ASFV within a pig house taking into account dynamics of ASFV spread and the unit size. The tool can be implemented in simulation models of ASFV spread between herds. PMID- 26870741 TI - Modeling Classical Swine Fever Outbreak-Related Outcomes. AB - The study was carried out to estimate classical swine fever (CSF) outbreak related outcomes, such as epidemic duration and number of infected, vaccinated, and depopulated premises, using defined most likely CSF outbreak scenarios. Risk metrics were established using empirical data to select the most likely CSF outbreak scenarios in Indiana. These scenarios were simulated using a stochastic between-premises disease spread model to estimate outbreak-related outcomes. A total of 19 single-site (i.e., with one index premises at the onset of an outbreak) and 15 multiple-site (i.e., with more than one index premises at the onset of an outbreak) outbreak scenarios of CSF were selected using the risk metrics. The number of index premises in the multiple-site outbreak scenarios ranged from 4 to 32. The multiple-site outbreak scenarios were further classified into clustered (N = 6) and non-clustered (N = 9) groups. The estimated median (5th, 95th percentiles) epidemic duration (days) was 224 (24, 343) in the single site and was 190 (157, 251) and 210 (167, 302) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. The median (5th, 95th percentiles) number of infected premises was 323 (0, 488) in the single-site outbreak scenarios and was 529 (395, 662) and 465 (295, 640) in the clustered and non-clustered multiple-site outbreak scenarios, respectively. Both the number and spatial distributions of the index premises affected the outcome estimates. The results also showed the importance of implementing vaccinations to accommodate depopulation in the CSF outbreak controls. The use of routinely collected surveillance data in the risk metrics and disease spread model allows end users to generate timely outbreak-related information based on the initial outbreak's characteristics. Swine producers can use this information to make an informed decision on the management of swine operations and continuity of business, so that potential losses could be minimized during a CSF outbreak. Government authorities might use the information to make emergency preparedness plans for CSF outbreak control. PMID- 26870742 TI - Wavefront-optimized surface retreatments of refractive error following previous laser refractive surgery: a retrospective study. AB - BACKGROUND: Retreatments are sometimes necessary to correct residual or induced refractive errors following refractive surgery. Many different combinations of primary treatment methods and retreatment techniques have been studied, however, few studies have investigated wavefront-optimized (WFO) technology for retreatment following primary refractive surgery. This study aimed to report the outcomes of WFO photorefractive keratectomy (PRK) retreatments of refractive error following previous laser refractive surgery with PRK, laser in situ keratomileusis (LASIK), or laser-assisted subepithelial keratectomy (LASEK). METHODS: We reviewed records of patients who underwent WFO PRK retreatments using the Allegretto Wave Eye-Q 400 Hz Excimer Laser System (Alcon Surgical) between January 2008 and April 2011 at Walter Reed Army Medical Center and Madigan Army Medical Center. Outcomes were recorded in terms of uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent (MRSE), corrected distance visual acuity (CDVA), and complications at 1 month (M), 3 M, and 6 M post-op. RESULTS: Seventy-eight patients (120 eyes) underwent WFO PRK retreatment during the study period. Primary surgery was surface ablation in 87 eyes (78 PRK, 9 LASEK) and LASIK in 33 eyes. The mean spherical equivalent before retreatment was -0.79 +/- 0.94 D (-3.00 to 1.88 D). UDVA was >= 20/20 in 69 eyes (60.0 %) at 1 M, 54 eyes (71.1 %) at 3 M, and 27 eyes (73.0 %) at 6 M follow-up. MRSE was within +/-0.50 D of emmetropia in 78 eyes (67.8 %) at 1 M, 59 eyes (77.6 %) at 3 M, and 25 eyes (67.6 %) at 6 M follow-up. CDVA was maintained within +/-1 line of pre-op in 113 of 115 eyes (98.3 %) at 1 M, 74 of 76 eyes (97.4 %) at 3 M, and 37 eyes (100 %) at 6 M follow-up. CONCLUSION: Although follow-up was limited beyond 3 M, WFO PRK retreatments in patients with residual refractive error may be a safe and effective procedure. Further studies are necessary to determine the long term safety and stability of outcomes. PMID- 26870743 TI - Guiding Principles for Data Architecture to Support the Pathways Community HUB Model. AB - INTRODUCTION: The Pathways Community HUB Model provides a unique strategy to effectively supplement health care services with social services needed to overcome barriers for those most at risk of poor health outcomes. Pathways are standardized measurement tools used to define and track health and social issues from identification through to a measurable completion point. The HUB use Pathways to coordinate agencies and service providers in the community to eliminate the inefficiencies and duplication that exist among them. PATHWAYS COMMUNITY HUB MODEL AND FORMALIZATION: Experience with the Model has brought out the need for better information technology solutions to support implementation of the Pathways themselves through decision-support tools for care coordinators and other users to track activities and outcomes, and to facilitate reporting. Here we provide a basis for discussing recommendations for such a data infrastructure by developing a conceptual model that formalizes the Pathway concept underlying current implementations. REQUIREMENTS FOR DATA ARCHITECTURE TO SUPPORT THE PATHWAYS COMMUNITY HUB MODEL: The main contribution is a set of core recommendations as a framework for developing and implementing a data architecture to support implementation of the Pathways Community HUB Model. The objective is to present a tool for communities interested in adopting the Model to learn from and to adapt in their own development and implementation efforts. PROBLEMS WITH QUALITY OF DATA EXTRACTED FROM THE CHAP DATABASE: Experience with the Community Health Access Project (CHAP) data base system (the core implementation of the Model) has identified several issues and remedies that have been developed to address these issues. Based on analysis of issues and remedies, we present several key features for a data architecture meeting the just mentioned recommendations. IMPLEMENTATION OF FEATURES: Presentation of features is followed by a practical guide to their implementation allowing an organization to consider either tailoring off-the-shelf generic systems to meet the requirements or offerings that are specialized for community-based care coordination. DISCUSSION: Looking to future extensions, we discuss the utility and prospects for an ontology to include care coordination in the Unified Medical Language System (UMLS) of the National Library of Medicine and other existing medical and nursing taxonomies. CONCLUSIONS AND RECOMMENDATIONS: Pathways structures are an important principle, not only for organizing the care coordination activities, but also for structuring the data stored in electronic form in the conduct of such care. We showed how the proposed architecture encourages design of effective decision support systems for coordinated care and suggested how interested organizations can set about acquiring such systems. Although the presentation focuses on the Pathways Community HUB Model, the principles for data architecture are stated in generic form and are applicable to any health information system for improving care coordination services and population health. PMID- 26870744 TI - Improved pulmonary nodule classification utilizing quantitative lung parenchyma features. AB - Current computer-aided diagnosis (CAD) models for determining pulmonary nodule malignancy characterize nodule shape, density, and border in computed tomography (CT) data. Analyzing the lung parenchyma surrounding the nodule has been minimally explored. We hypothesize that improved nodule classification is achievable by including features quantified from the surrounding lung tissue. To explore this hypothesis, we have developed expanded quantitative CT feature extraction techniques, including volumetric Laws texture energy measures for the parenchyma and nodule, border descriptors using ray-casting and rubber-band straightening, histogram features characterizing densities, and global lung measurements. Using stepwise forward selection and leave-one-case-out cross validation, a neural network was used for classification. When applied to 50 nodules (22 malignant and 28 benign) from high-resolution CT scans, 52 features (8 nodule, 39 parenchymal, and 5 global) were statistically significant. Nodule only features yielded an area under the ROC curve of 0.918 (including nodule size) and 0.872 (excluding nodule size). Performance was improved through inclusion of parenchymal (0.938) and global features (0.932). These results show a trend toward increased performance when the parenchyma is included, coupled with the large number of significant parenchymal features that support our hypothesis: the pulmonary parenchyma is influenced differentially by malignant versus benign nodules, assisting CAD-based nodule characterizations. PMID- 26870745 TI - Association of computerized texture features on MRI with early treatment response following laser ablation for neuropathic cancer pain: preliminary findings. AB - Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment modality for cancer pain management that targets the cingulum (pain center in the brain) and has shown promise over radio frequency (RF)-based ablation, due to magnetic resonance image (MRI) guidance that allows for precise ablation. Since laser ablation for pain management is currently exploratory and is only performed at a few centers worldwide, its short- and long-term effects on the cingulum are currently unknown. Traditionally, treatment effects for neurological conditions are evaluated by monitoring changes in intensities and/or volume of the ablation zone on post-treatment Gadolinium-contrast T1-w (Gd-T1) MRI. However, LITT introduces subtle localized changes corresponding to tissues response to treatment, which may not be appreciable on visual inspection of volumetric or intensity changes. Additionally, different MRI protocols [Gd-T1, T2w, gradient echo sequence (GRE), fluid-attenuated inversion recovery (FLAIR)] are known to capture complementary diagnostic information regarding the patient's response to treatment; the utility of these MRI protocols has so far not been investigated to evaluate early and localized response to LITT treatment in the context of neuropathic cancer pain. In this work, we present the first attempt at (a) examining early treatment-related changes on a per-voxel basis via quantitative comparison of computer-extracted texture descriptors across pre- and post-LITT multiparametric (MP-MRI) (Gd-T1, T2w, GRE, FLAIR), subtle microarchitectural texture changes that may not be appreciable on original MR intensities or volumetric differences, and (b) investigating the efficacy of different MRI protocols in accurately capturing immediate post-treatment changes reflected (1) within and (2) outside the ablation zone. A retrospective cohort of four patient studies comprising pre- and immediate (24 h) post-LITT 3 Tesla Gd-T1, T2w, GRE, and FLAIR acquisitions was considered. Our quantitative approach first involved intensity standardization to allow for grayscale MR intensities acquired pre- and post-LITT to have a fixed tissue-specific meaning within the same imaging protocol, the same body region, and within the same patient. An affine registration was then performed on individual post-LITT MRI protocols to a reference MRI protocol pre-LITT. A total of 78 computerized texture features (co occurrence matrix homogeneity, neighboring gray-level dependence matrix, Gabor) are then extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxelwise comparison of the changes in MRI texture features between pre- and post-LITT MRI indicate that (a) Gabor texture features at specific orientations were highly sensitive as well as specific in predicting subtle microarchitectural changes within and around the ablation zone pre- and post LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate potential for noninvasive computerized MP-MRI features over volumetric features in determining localized microarchitectural early focal treatment changes post-LITT for neuropathic cancer pain treatment. PMID- 26870747 TI - Consistency of visual assessments of mammographic breast density from vendor specific "for presentation" images. AB - Discussions of percent breast density (PD) and breast cancer risk implicitly assume that visual assessments of PD are comparable between vendors despite differences in technology and display algorithms. This study examines the extent to which visual assessments of PD differ between mammograms acquired from two vendors. Pairs of "for presentation" digital mammography images were obtained from two mammography units for 146 women who had a screening mammogram on one vendor unit followed by a diagnostic mammogram on a different vendor unit. Four radiologists independently visually assessed PD from single left mediolateral oblique view images from the two vendors. Analysis of variance, intra-class correlation coefficients (ICC), scatter plots, and Bland-Altman plots were used to evaluate PD assessments between vendors. The mean radiologist PD for each image was used as a consensus PD measure. Overall agreement of the PD assessments was excellent between the two vendors with an ICC of 0.95 (95% confidence interval: 0.93 to 0.97). Bland-Altman plots demonstrated narrow upper and lower limits of agreement between the vendors with only a small bias (2.3 percentage points). The results of this study support the assumption that visual assessment of PD is consistent across mammography vendors despite vendor-specific appearances of "for presentation" images. PMID- 26870746 TI - Image toggling saves time in mammography. AB - When two images are perfectly aligned, even subtle differences are readily detected when the images are "toggled" back and forth in the same location. However, substantial changes between two photographs can be missed if the images are misaligned ("change blindness"). Nevertheless, recent work from our lab, testing nonradiologists, suggests that toggling misaligned photographs leads to superior performance compared to side-by-side viewing (SBS). In order to determine if a benefit of toggling misaligned images may be observed in clinical mammography, we developed an image toggling technique where pairs of new and prior breast imaging exam images could be efficiently toggled back and forth. Twenty-three radiologists read 10 mammograms evenly divided in toggle and SBS modes. The toggle mode led to a 6-s benefit in reaching a decision [[Formula: see text], [Formula: see text]]. The toggle viewing mode also led to a 5% improvement in diagnostic accuracy, though in our small sample this effect was not statistically reliable. Time savings were found even though successive mammograms were not perfectly aligned. Given the ever-increasing caseload for radiologists, this simple manipulation of how the images are viewed could save valuable time in clinical practice, allowing radiologists to read more cases or spend more time on difficult cases. PMID- 26870748 TI - Radiologists remember mountains better than radiographs, or do they? AB - Expertise with encoding material has been shown to aid long-term memory for that material. It is not clear how relevant this expertise is for image memorability (e.g., radiologists' memory for radiographs), and how robust over time. In two studies, we tested scene memory using a standard long-term memory paradigm. One compared the performance of radiologists to naive observers on two image sets, chest radiographs and everyday scenes, and the other radiologists' memory with immediate as opposed to delayed recognition tests using musculoskeletal radiographs and forest scenes. Radiologists' memory was better than novices for images of expertise but no different for everyday scenes. With the heterogeneity of image sets equated, radiologists' expertise with radiographs afforded them better memory for the musculoskeletal radiographs than forest scenes. Enhanced memory for images of expertise disappeared over time, resulting in chance level performance for both image sets after weeks of delay. Expertise with the material is important for visual memorability but not to the same extent as idiosyncratic detail and variability of the image set. Similar memory decline with time for images of expertise as for everyday scenes further suggests that extended familiarity with an image is not a robust factor for visual memorability. PMID- 26870749 TI - Teaching search patterns to medical trainees in an educational laboratory to improve perception of pulmonary nodules. AB - The goal of this research is to demonstrate that teaching healthcare trainees a formal search or scan pattern for evaluation of the lungs improves their ability to identify pulmonary nodules on chest radiographs (CXRs). A group of physician assistant trainees were randomly assigned to control and experimental groups. Each group was shown two sets of CXRs, each set with a nodule prevalence of approximately 50%. The experimental group received search pattern training between case sets, whereas the control group did not. Both groups were asked to mark nodules when present and indicate their diagnostic confidence. Subject performance at nodule detection was quantified using changes in area under the localization receiver operating characteristic curve ([Formula: see text]). There was no significant improvement in performance between case sets for the control group. There was a significant improvement in subject performance after training for the experimental group, [Formula: see text], [Formula: see text]. These results demonstrate that teaching a search pattern to trainees improves their ability to identify nodules and decreases the number of perceptual errors in nodule identification, and suggest that our knowledge of medical image perception may be used to develop rational tools for the education of healthcare trainees. PMID- 26870750 TI - Brightness-preserving fuzzy contrast enhancement scheme for the detection and classification of diabetic retinopathy disease. AB - The contrast enhancement of retinal image plays a vital role for the detection of microaneurysms (MAs), which are an early sign of diabetic retinopathy disease. A retinal image contrast enhancement method has been presented to improve the MA detection technique. The success rate on low-contrast noisy retinal image analysis shows the importance of the proposed method. Overall, 587 retinal input images are tested for performance analysis. The average sensitivity and specificity are obtained as 95.94% and 99.21%, respectively. The area under curve is found as 0.932 for the receiver operating characteristics analysis. The classifications of diabetic retinopathy disease are also performed here. The experimental results show that the overall MA detection method performs better than the current state-of-the-art MA detection algorithms. PMID- 26870751 TI - Early age at menarche and wheezing in adolescence. The 1993 Pelotas (Brazil) birth cohort study. AB - OBJECTIVE: To evaluate the effect of menarche before 11 years of age on the incidence of wheezing/asthma in girls 11 to 18 years of age. METHODS: The study sample comprised 1,350 girls from a birth cohort that started in 1993 in the urban area of the city of Pelotas, southern Brazil; this cohort was followed until 18 years of age. We assessed wheezing by the question, "Have you ever had wheezing in the chest at any time in the past?," from the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Early menarche was defined as occurring before 11 years of age. We estimated the cumulative incidence of wheezing excluding from the analysis all those participants who reported wheezing before age of 11 years. We performed the chi-square test to assess the association between ever wheezing and independent variables. Poisson regression models with robust variance were used to estimate cumulative incidence ratios. RESULTS: The average age at menarche in the cohort girls was 12 years (95% CI: 11.1-12.1). The prevalence of early menarche before 11 years of age was 11% (95% CI: 9.7-12.3). The cumulative incidence of wheezing from 11 to 18 years of age was 33.5% (95% CI: 30.9- 36.0). The crude association between ever wheezing in adolescence and early menarche before age 11 was 1.19 (95% CI: 0.96 1.48). After adjusting for early childhood and contemporaneous variables, no significant association for early menarche before 11 years of age and wheezing during adolescence was found (CIR: 1.18; CI95%: 0.93-1.49). CONCLUSION: Early menarche before 11 years of age is not associated with an increased risk of wheezing during adolescence. PMID- 26870752 TI - Proteomic data on the nuclear interactome of human MCM9. AB - We present data relating to the interactome of MCM9 from the nuclei of human cells. MCM9 belongs to the AAA+ superfamily, and contains an MCM domain and motifs that may confer DNA helicase activity. MCM9 has been shown to bind MCM8, and has been implicated in DNA replication and homologous recombination. However, the mechanistic basis of MCM9's role in DNA repair is poorly understood, and proteins with which it interacts were hitherto unknown. We performed tandem affinity purification of MCM9 and its interacting proteins from nuclear extracts of human cells, followed by proteomic analysis, thereby generating a set of mass spectrometry data corresponding to the MCM9 interactome [1]. The proteomic data set comprises 29 mass spectrometry RAW files, deposited to the ProteomeXchange Consortium, and freely available from the PRIDE partner repository with the data set identifier PXD000212. A set of 22 interacting proteins identified from the proteomic data was used to create an MCM9-centered interactive network diagram, using the Cytoscape program. These data allow the scientific community to access, mine and explore the human nuclear MCM9 interactome. PMID- 26870753 TI - Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology. AB - The presented data provides additional information about the assessment of affinity purified nicotinic acetylcholine receptor (nAChR) rich membrane solubilized with long chain (16 saturated carbons) lysophospholipid with glycerol headgroup (LFG-16). The assessment of stability and functionality of solubilized membrane protein is a critical step prior to further crystallization trails. One of the key factors for this task is the appropriate choice of a detergent that can support nAChR activity and stability comparable to the crude membranes. The stability of the nAChR-LFG-16 complex incorporated into lipid cubic phase (LCP) was monitored for a period of 30 days by means of fluorescence recovery after photobleaching (FRAP) and the functionality was evaluated after its incorporation into Xenopus oocyte by means of the two electrode voltage clamp technique. PMID- 26870754 TI - Data for the crystal structure of APRIL-BAFF-BAFF heterotrimer. AB - The TNF family ligands B cell activation factor (BAFF) and a proliferation inducing ligand (APRIL) modulate B cell function by forming homotrimers and heterotrimers. To determine the structure of a heterotrimer of BAFF and APRIL, these ligands were expressed as a single chain protein in HEK 293 cells, purified by affinity and size exclusion chromatographies, and crystallized. Crystals belonging to the orthorhombic crystal system with a space group of C2221 diffracted to 2.43 A. Initial structural solution was obtained by the molecular replacement method, and the structure was further refined to an R factor of 0.179 and free R factor of 0.234. The atomic coordinates and structure factors have been deposited into the Protein Data Bank (accession code 4ZCH). PMID- 26870755 TI - Proteome-wide dataset supporting the study of ancient metazoan macromolecular complexes. AB - Our analysis examines the conservation of multiprotein complexes among metazoa through use of high resolution biochemical fractionation and precision mass spectrometry applied to soluble cell extracts from 5 representative model organisms Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Strongylocentrotus purpuratus, and Homo sapiens. The interaction network obtained from the data was validated globally in 4 distant species (Xenopus laevis, Nematostella vectensis, Dictyostelium discoideum, Saccharomyces cerevisiae) and locally by targeted affinity-purification experiments. Here we provide details of our massive set of supporting biochemical fractionation data available via ProteomeXchange (PXD002319-PXD002328), PPIs via BioGRID (185267); and interaction network projections via (http://metazoa.med.utoronto.ca) made fully accessible to allow further exploration. The datasets here are related to the research article on metazoan macromolecular complexes in Nature [1]. PMID- 26870757 TI - Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg) Kausel). AB - Jaboticaba (Plinia trunciflora (O. Berg) Kausel) is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase) activity and ATP biosynthesis of human lung fibroblast cells (MRC-5) treated with amiodarone. The data presented in this article demonstrate that the polyphenols rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells. PMID- 26870756 TI - Dataset for a case report of a homozygous PEX16 F332del mutation. AB - This dataset provides a clinical description along with extensive biochemical and molecular characterization of a patient with a homozygous mutation in PEX16 with an atypical phenotype. This patient described in Molecular Genetics and Metabolism Reports was ultimately diagnosed with an atypical peroxisomal disorder on exome sequencing. A clinical timeline and diagnostic summary, results of an extensive plasma and fibroblast analysis of this patient's peroxisomal profile is provided. In addition, a table of additional variants from the exome analysis is provided. PMID- 26870758 TI - Thermal sensitivity analysis data utilizing Q10 scanning, Boltzmann slope factor and the change of molar heat capacity. AB - As a further elaboration of the recently devised Q10 scanning analysis ("Exceptionally high thermal sensitivity of rattlesnake TRPA1 correlates with peak current amplitude" [1]), the interval between current data points at two temperatures was shortened and the resulting parameters representing thermal sensitivities such as peak Q10s and temperature points of major thermosensitivity events are presented for two TRPA1 orthologues from rattlesnakes and boas. In addition, the slope factors from Boltzmann fitting and the change of molar heat capacity of temperature-evoked currents were evaluated and compared as alternative ways of thermal sensitivity appraisal of TRPA1 orthologues. PMID- 26870759 TI - Data on the standardization of a cyclohexanone-responsive expression system for Gram-negative bacteria. AB - Engineering of robust microbial cell factories requires the use of dedicated genetic tools somewhat different from those traditionally used for laboratory adapted microorganisms. We have edited and formatted the ChnR/P chnB regulatory node of Acinetobacter johnsonii to ease the targeted engineering of ectopic gene expression in Gram-negative bacteria. The proposed compositional standard was thoroughly verified with a monomeric and superfolder green fluorescent protein (msf*GFP) in Escherichia coli. The expression data presented reflect a tightly controlled transcription initiation signal in response to cyclohexanone. Data in this article are related to the research paper "Genetic programming of catalytic Pseudomonas putida biofilms for boosting biodegradation of haloalkanes" [1]. PMID- 26870760 TI - Exogenous control over intracellular acidification: Enhancement via proton caged compounds coupled to gold nanoparticles and an alternative pathway with DMSO. AB - Proton caged compounds exhibit a characteristic behavior when directly dosed into cells or being coupled to gold nanoparticles prior to the dosing. When irradiated in the near ultraviolet region, they release protons that interact with intracellular HCO3 (-) to yield H2CO3. The dissociation of carbonic acid, then, releases CO2 that can be distinctively singled out in infrared spectra. In the process of searching a pathway to augment the intracellular uptake of proton caged compounds, we probed the association of 1-(2-nitrophenyl)-ethylhexadecyl sulfonate (HDNS) with DMSO, an agent to enhance the membrane permeability. We found out a different UV-induced protonation mechanism that opens up to new conduits of employing of proton caged compounds. Here, we report the infrared data we collected in this set of experiments. PMID- 26870761 TI - Validation and application of the personnel factor for the garment used in cleanrooms. AB - The cleanroom environment has many potential sources of contamination, including: operators, equipment, structures, and any surface that can create particles via friction, heat, exhaust, outgassing, and static electricity charge. Operatives working in the cleanroom are the major source of particles. While cleanroom operators work, they emit millions of particles from every activity. Particles migrate up the cleanroom garment to the head and drop to the legs during cleanroom movements. Specialized textile fabrics have been used in cleanroom garments for many years. The need for this type of fabric has increased mainly due to the need to protect critical operations in cleanrooms as well as creating comfort for operators and other personnel. This study covers the general static wind-driven method, the Helmke Drum method and the dispersal chamber to measure particle penetration, shedding, and generation, in regards to the filtration efficiency of cleanroom fabrics and garments. Firstly, particle penetration is shown to increase with increasing face velocity and decreasing particle size below 1 MUm. Secondly, that a recommended upper particle-size limit should be 5 um. Using the Helmke drum test, the size distribution of particles released from the garment is shown to follow a power law distribution, with a slope of less than 1. Furthermore, the study introduces dynamic body box for testing fabrics as well as cleanroom garments. It is more practical and sensitive when compared to traditional methods and is based on a more concise technical approach. The life time cycle performance of a typical cleanroom garment coverall is examined, particularly looking at the implications of pre-use steralization. PMID- 26870762 TI - Increasing Healthspan: Prosper and Live Long. PMID- 26870763 TI - Mesenchymal Stem Cells and their Potential for Microengineering the Chondrocyte Niche. PMID- 26870764 TI - The Colon as the Potassium Target: Entering the Colonic Age of Hyperkalemia Treatment? PMID- 26870765 TI - Hepatitis E In Transplant Recipients: Why Is This Not A Problem In Japan? PMID- 26870766 TI - Improving Exploitation of Whole Genome Sequencing Data for Public Health, Forensic Microbiology and Biosafety. PMID- 26870767 TI - Linezolid for Treating Tuberculosis: A Delicate Balancing Act. PMID- 26870768 TI - Tuberculous Pericarditis: A Complex Puzzle to Put Together. PMID- 26870769 TI - Are the Present Doses of Anti Tubercular Drugs Adequate for Severe Disease? PMID- 26870770 TI - Bromodomain Blockade for Intimal Hyperplasia--A Good BET? PMID- 26870771 TI - Stable Coronary Artery Disease Patients: Different Practice Patterns in Everyday Clinical Situations. PMID- 26870772 TI - Haemoglobin C Promotes Distinct Membrane Properties in Heterozygous HbSC red Cells. PMID- 26870773 TI - Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer: Epithelial Mesenchymal Transition (EMT), the Missing Link? PMID- 26870774 TI - Chronic Obstructive Pulmonary Disease, Neutrophils and Bacterial Infection: A Complex Web Involving IL-17 and IL-22 Unravels. PMID- 26870775 TI - Muscle specific iron deficiency has systemic consequences. PMID- 26870776 TI - Mimecan: A Newly Identified Adipokine and Regulator of Appetite. PMID- 26870777 TI - Famine From Feast: Low Red Cell Vitamin C Levels in Diabetes. PMID- 26870778 TI - Emerging Role of VEGFC in Pathological Angiogenesis. PMID- 26870779 TI - Syk and Yea Shall Find. PMID- 26870780 TI - The pons and human affective processing--Implications for Parkinson's disease. PMID- 26870781 TI - Predicting Molecular Models: Where Are We Going? PMID- 26870782 TI - Arterial or Venous: Where Are the Circulating Tumor Cells? PMID- 26870783 TI - Differences in Uptake of Risk Reduction Strategies Among Underserved Populations. PMID- 26870784 TI - A Novel Class of Small Molecule Compounds that Inhibit Hepatitis C Virus Infection by Targeting the Prohibitin-CRaf Pathway. AB - Identification of novel drug targets and affordable therapeutic agents remains a high priority in the fight against chronic hepatitis C virus (HCV) infection. Here, we report that the cellular proteins prohibitin 1 (PHB1) and 2 (PHB2) are pan-genotypic HCV entry factors functioning at a post-binding step. While predominantly found in mitochondria, PHBs localize to the plasma membrane of hepatocytes through their transmembrane domains and interact with both EGFR and CRaf. Targeting PHB by rocaglamide (Roc-A), a natural product that binds PHB1 and 2, reduced cell surface PHB1 and 2, disrupted PHB-CRaf interaction, and inhibited HCV entry at low nanomolar concentrations. A structure-activity analysis of 32 synthetic Roc-A analogs indicated that the chiral, racemic version of aglaroxin C, a natural product biosynthetically related to Roc-A, displayed improved potency and therapeutic index against HCV infection. This study reveals a new class of HCV entry inhibitors that target the PHB1/2-CRaf pathway. PMID- 26870785 TI - A Nationwide Survey of Hepatitis E Virus Infection and Chronic Hepatitis E in Liver Transplant Recipients in Japan. AB - BACKGROUND: Recently, chronic hepatitis E has been increasingly reported in organ transplant recipients in European countries. In Japan, the prevalence of hepatitis E virus (HEV) infection after transplantation remains unclear, so we conducted a nationwide cross-sectional study to clarify the prevalence of chronic HEV infection in Japanese liver transplant recipients. METHODS: A total of 1893 liver transplant recipients in 17 university hospitals in Japan were examined for the presence of immunoglobulin G (IgG), IgM and IgA classes of anti-HEV antibodies, and HEV RNA in serum. FINDINGS: The prevalence of anti-HEV IgG, IgM and IgA class antibodies was 2.9% (54/1893), 0.05% (1/1893) and 0% (0/1893), respectively. Of 1651 patients tested for HEV RNA, two patients (0.12%) were found to be positive and developed chronic infection after liver transplantation. In both cases, HEV RNA was also detected in one of the blood products transfused at the perioperative period. Analysis of the HEV genomes revealed that the HEV isolates obtained from the recipients and the transfused blood products were identical in both cases, indicating transfusion-transmitted HEV infection. INTERPRETATION: The prevalence of HEV antibodies in liver transplant recipients was 2.9%, which is low compared with the healthy population in Japan and with organ transplant recipients in European countries; however, the present study found, for the first time, two Japanese patients with chronic HEV infection that was acquired via blood transfusion during or after liver transplantation. PMID- 26870786 TI - Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years. AB - BACKGROUND: Anthrax is a rare disease in humans but elicits great public fear because of its past use as an agent of bioterrorism. Injectional anthrax has been occurring sporadically for more than ten years in heroin consumers across multiple European countries and this outbreak has been difficult to trace back to a source. METHODS: We took a molecular epidemiological approach in understanding this disease outbreak, including whole genome sequencing of Bacillus anthracis isolates from the anthrax victims. We also screened two large strain repositories for closely related strains to provide context to the outbreak. FINDINGS: Analyzing 60 Bacillus anthracis isolates associated with injectional anthrax cases and closely related reference strains, we identified 1071 Single Nucleotide Polymorphisms (SNPs). The synapomorphic SNPs (350) were used to reconstruct phylogenetic relationships, infer likely epidemiological sources and explore the dynamics of evolving pathogen populations. Injectional anthrax genomes separated into two tight clusters: one group was exclusively associated with the 2009-10 outbreak and located primarily in Scotland, whereas the second comprised more recent (2012-13) cases but also a single Norwegian case from 2000. INTERPRETATION: Genome-based differentiation of injectional anthrax isolates argues for at least two separate disease events spanning > 12 years. The genomic similarity of the two clusters makes it likely that they are caused by separate contamination events originating from the same geographic region and perhaps the same site of drug manufacturing or processing. Pathogen diversity within single patients challenges assumptions concerning population dynamics of infecting B. anthracis and host defensive barriers for injectional anthrax. FUNDING: This work was supported by the United States Department of Homeland Security grant no. HSHQDC-10-C-00,139 and via a binational cooperative agreement between the United States Government and the Government of Germany. This work was supported by funds from the German Ministry of Defense (Sonderforschungsprojekt 25Z1-S-431,214). Support for sequencing was also obtained from Illumina, Inc. These sources had no role in the data generation or interpretation, and had not role in the manuscript preparation. PANEL 1 RESEARCH IN CONTEXT SYSTEMATIC REVIEW: We searched PubMed for any article published before Jun. 17, 2015, with the terms "Bacillus anthracis" and "heroin", or "injectional anthrax". Other than our previously published work (Price et al., 2012), we found no other relevant studies on elucidating the global phylogenetic relationships of B. anthracis strains associated with injectional anthrax caused by recreational heroin consumption of spore-contaminated drug. There were, however, publically available genome sequences of two strains involved (Price et al., 2012, Grunow et al., 2013) and the draft genome sequence of Bacillus anthracis UR-1, isolated from a German heroin user (Ruckert et al., 2012) with only limited information on the genotyping of closely related strains (Price et al., 2012, Grunow et al., 2013). LAY PERSON INTERPRETATION: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a > 12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution. PMID- 26870787 TI - Distinct Transcriptional and Anti-Mycobacterial Profiles of Peripheral Blood Monocytes Dependent on the Ratio of Monocytes: Lymphocytes. AB - The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio. Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were characterised by microarray. Transcript expression was tested for association with ML ratio calculated from leucocyte differential counts by linear regression. The ML ratio was associated with mycobacterial growth in vitro (beta = 2.23, SE 0.91, p = 0.02). Using sorted monocytes and lymphocytes, in vivo ML ratio (% variance explained R(2) = 11%, p = 0.02) dominated over in vitro ratios (R(2) = 5%, p = 0.10) in explaining mycobacterial growth. Expression of 906 genes was associated with the ML ratio and 53 with monocyte count alone. ML-ratio associated genes were enriched for type-I and -II interferon signalling (p = 1.2 * 10(- 8)), and for genes under transcriptional control of IRF1, IRF2, RUNX1, RELA and ESRRB. The ML-ratio associated gene set was enriched in TB disease (3.11-fold, 95% CI: 2.28-4.19, p = 5.7 * 10(- 12)) and other inflammatory diseases including atopy, HIV, IBD and SLE. The ML ratio is associated with distinct transcriptional and anti mycobacterial profiles of monocytes that may explain the disease associations of the ML ratio. PMID- 26870788 TI - Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis. AB - Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3.10, 95% CI 1.23-7 . 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0.004) or 600 mg (P < 0.0001). Increasing mean linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's rho = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 MUg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use. PMID- 26870789 TI - Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality. AB - BACKGROUND: Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. METHODS: Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. FINDINGS: Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20-71) years. The median, follow up was for 11.97 (range: 0.03 74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4-58) days or 3.91(range: 0.5-8.96) log10CFU/mL, which overlapped with the range of 3.24-7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5.23 months on directly observed therapy, a CD4 + count of <= 199.5/mL, and TTP <= 14 days (bacillary load >= 5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. INTERPRETATION: Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drives mortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition. PMID- 26870790 TI - Poor Penetration of Antibiotics Into Pericardium in Pericardial Tuberculosis. AB - Pericardial tuberculosis (TB) is associated with high therapy failure and high mortality rates. Antibiotics have to penetrate to site of infection at sufficient non-protein bound concentrations, and then enter bacteria to inhibit intracellular biochemical processes. The antibiotic concentrations achieved in pericardial fluid in TB pericarditis have never been measured before. We recruited two cohorts of patients with TB pericarditis, and left a pigtail catheter in-situ for serial drug concentration measurements over 24 h. Altogether, 704 drug concentrations were comodeled for pharmacokinetic analyses. The drug concentrations achieved in pericardial fluid were compared to the minimum inhibitory concentrations (MICs) of clinical Mycobacterium tuberculosis isolates. The total rifampicin concentration pericardial-to-serum ratios in 16 paired samples were 0.19 +/- 0.33. The protein concentrations of the pericardial fluid in TB pericarditis were observed to be as high as in plasma. The non protein bound rifampicin concentrations in pericardial fluid were 4-fold lower than rifampicin MICs in the pilot study, and the peak concentration was 0.125 versus 0.208 mg/L in the second (p = 0.001). The rifampicin clearance from pericardial fluid was 9.45 L/h versus 7.82 L/h in plasma (p = 0.002). Ethambutol peak concentrations had a pericardial-to-plasma ratio of 0.55 +/- 0.22; free ethambutol peak concentrations were 2.30-lower than MICs (p < 0.001). The pericardial fluid pH was 7.34. The median pyrazinamide peak concentrations were 42.93 mg/L versus a median MIC of 800 mg/L at pH 7.34 (p < 0.0001). There was no significant difference between isoniazid pericardial fluid and plasma concentrations, and isoniazid peak concentrations were above MIC. This is the first study to measure anti-TB drug concentrations, pH and protein in the pericardial TB fluid. Pericardial concentrations of the key sterilizing drugs for TB were below MIC, which could contribute to poor outcomes. A new regimen that overcomes these limitations might need to be crafted. PMID- 26870791 TI - BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries. AB - BACKGROUND: Intimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic "readers" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known. METHODS: We investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model. RESULTS: While BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(-), substantially down regulated PDGF receptor-alpha which, in JQ1(+)-treated arteries versus vehicle control, was also reduced. CONCLUSIONS: Blocking BET bromodomains mitigates neointima formation, suggesting an epigenetic approach for effective prevention of intimal hyperplasia and associated vascular diseases. PMID- 26870792 TI - Practice Patterns for Outpatients With Stable Coronary Artery Disease: A Case Vignette-based Survey Among French Cardiologists. AB - BACKGROUND: Although medical management of patients with coronary artery disease (CAD) is often based on scientific guidelines, a number of everyday clinical situations are not specifically covered by recommendations or the level of evidence is low. The aim of this study was to assess practice patterns regarding routine management of patients with stable CAD. METHODS: A survey comprising six questions on two clinical scenarios regarding stable CAD management was sent to 345 cardiologists from the Nord-Pas-de-Calais Region (France). We first assessed practice patterns globally and then searched for associations with physician characteristics (age, gender, sub-specialty, and type of practice). FINDINGS: The response rate was 92%. Regarding management of asymptomatic CAD, 86% of the cardiologists performed routine exercise testing, before which, 69% withdrew beta blockers. After a positive exercise test, 26% immediately performed coronary angiography and 67%, further imaging tests. In the absence of left ventricular dysfunction or history of myocardial infarction, routine beta-blocker prescription for stable CAD was selected by 43%. When anticoagulation was needed for atrial fibrillation, 41% initiated direct oral anticoagulants rather than vitamin-K antagonists and 50% combined aspirin with anticoagulants. For recurrent stable angina in patients with known CAD, 24% performed coronary angiography directly, 49% requested a stress test, and 27% opted for medical therapy without further diagnostic testing. Age, gender of the cardiologist, academic environment, and practice of interventional cardiology were associated with certain management patterns. INTERPRETATION: When not guided by high-level recommendations, practice patterns for routine clinical situations in stable CAD vary considerably. Future clinical trials should address these clinical interrogations. PMID- 26870793 TI - Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype). AB - Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease. PMID- 26870795 TI - IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease. AB - Progression of chronic obstructive pulmonary disease (COPD) is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS) and to stimulate peripheral blood mononuclear cells (PBMC) from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1beta and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1beta and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation. PMID- 26870794 TI - Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium. AB - BACKGROUND: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. METHODS: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. FINDINGS: Significant dose-response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%quit_for_5-9 years to 89%quit_for_>= 20 years declined SCLC risk vs. subjects who had quit smoking < 5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects. INTERPRETATION: This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study. PMID- 26870796 TI - Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle. AB - Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid beta oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders. PMID- 26870797 TI - Mimecan, a Hormone Abundantly Expressed in Adipose Tissue, Reduced Food Intake Independently of Leptin Signaling. AB - Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in A(y)/a and db/db mice. Furthermore, the expression of interleukin (IL)-1beta and IL-6 was up regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1beta and IL-6 expression in the hypothalamus. PMID- 26870798 TI - Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure. AB - Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 MUg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naive recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naive recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism. PMID- 26870799 TI - Low Red Blood Cell Vitamin C Concentrations Induce Red Blood Cell Fragility: A Link to Diabetes Via Glucose, Glucose Transporters, and Dehydroascorbic Acid. AB - Strategies to prevent diabetic microvascular angiopathy focus on the vascular endothelium. Because red blood cells (RBCs) are less deformable in diabetes, we explored an original concept linking decreased RBC deformability to RBC ascorbate and hyperglycemia. We characterized ascorbate concentrations from human and mouse RBCs and plasma, and showed an inverse relationship between RBC ascorbate concentrations and deformability, measured by osmotic fragility. RBCs from ascorbate deficient mice were osmotically sensitive, appeared as spherocytes, and had decreased beta-spectrin. These aberrancies reversed with ascorbate repletion in vivo. Under physiologic conditions, only ascorbate's oxidation product dehydroascorbic acid (DHA), a substrate for facilitated glucose transporters, was transported into mouse and human RBCs, with immediate intracellular reduction to ascorbate. In vitro, glucose inhibited entry of physiologic concentrations of dehydroascorbic acid into mouse and human RBCs. In vivo, plasma glucose concentrations in normal and diabetic mice and humans were inversely related to respective RBC ascorbate concentrations, as was osmotic fragility. Human RBC beta spectrin declined as diabetes worsened. Taken together, hyperglycemia in diabetes produced lower RBC ascorbate with increased RBC rigidity, a candidate to drive microvascular angiopathy. Because glucose transporter expression, DHA transport, and its inhibition by glucose differed for mouse versus human RBCs, human experimentation is indicated. PMID- 26870800 TI - Inhibition of Cyclic Adenosine Monophosphate (cAMP)-response Element-binding Protein (CREB)-binding Protein (CBP)/beta-Catenin Reduces Liver Fibrosis in Mice. AB - Wnt/beta-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of beta-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the effects of PRI-724, a selective inhibitor of the cAMP-response element-binding protein-binding protein (CBP)/beta-catenin interaction, on liver fibrosis were examined using carbon tetrachloride (CCl4)- or bile duct ligation (BDL)-induced mouse liver fibrosis models. Following repetitive CCl4 administrations, the nuclear translocation of beta-catenin was observed only in the non-parenchymal cells in the liver. PRI-724 treatment reduced the fibrosis induced by CCl4 or BDL. C-82, an active form of PRI-724, inhibited the activation of isolated primary mouse quiescent hepatic stellate cells (HSCs) and promoted cell death in culture-activated HSCs. During the fibrosis resolution period, an increase in F4/80(+) CD11b(+) and Ly6C(low) CD11b(+) macrophages was induced by CCl4 and was sustained for two weeks thereafter, even after having stopped CCl4 treatment. PRI-724 accelerated the resolution of CCl4-induced liver fibrosis, and this was accompanied by increased matrix metalloproteinase (MMP)-9, MMP-2, and MMP-8 expression in intrahepatic leukocytes. In conclusion, targeting the CBP/beta-catenin interaction may become a new therapeutic strategy in treating liver fibrosis. PMID- 26870801 TI - Environmental Enteropathy, Oral Vaccine Failure and Growth Faltering in Infants in Bangladesh. AB - BACKGROUND: Environmental enteropathy (EE) is a subclinical enteric condition found in low-income countries that is characterized by intestinal inflammation, reduced intestinal absorption, and gut barrier dysfunction. We aimed to assess if EE impairs the success of oral polio and rotavirus vaccines in infants in Bangladesh. METHODS: We conducted a prospective observational study of 700 infants from an urban slum of Dhaka, Bangladesh from May 2011 to November 2014. Infants were enrolled in the first week of life and followed to age one year through biweekly home visits with EPI vaccines administered and growth monitored. EE was operationally defied as enteric inflammation measured by any one of the fecal biomarkers reg1B, alpha-1-antitrypsin, MPO, calprotectin, or neopterin. Oral polio vaccine success was evaluated by immunogenicity, and rotavirus vaccine response was evaluated by immunogenicity and protection from disease. This study is registered with ClinicalTrials.gov, number NCT01375647. FINDINGS: EE was present in greater than 80% of infants by 12 weeks of age. Oral poliovirus and rotavirus vaccines failed in 20.2% and 68.5% of the infants respectively, and 28.6% were malnourished (HAZ < - 2) at one year of age. In contrast, 0%, 9.0%, 7.9% and 3.8% of infants lacked protective levels of antibody from tetanus, Haemophilus influenzae type b, diphtheria and measles vaccines respectively. EE was negatively associated with oral polio and rotavirus response but not parenteral vaccine immunogenicity. Biomarkers of systemic inflammation and measures of maternal health were additionally predictive of both oral vaccine failure and malnutrition. The selected biomarkers from multivariable analysis accounted for 46.3% variation in delta HAZ. 24% of Rotarix(r) IgA positive individuals can be attributed to the selected biomarkers. INTERPRETATION: EE as well as systemic inflammation and poor maternal health were associated with oral but not parenteral vaccine underperformance and risk for future growth faltering. These results offer a potential explanation for the burden of these problems in low-income problems, allow early identification of infants at risk, and suggest pathways for intervention. FUNDING: The Bill and Melinda Gates Foundation (OPP1017093). PMID- 26870802 TI - Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling. AB - Retinal neovascularization is the most common cause of moderate to severe vision loss in all age groups. Despite the use of anti-VEGFA therapies, this complication continues to cause blindness, suggesting a role for additional molecules in retinal neovascularization. Besides VEGFA and VEGFB, hypoxia induced VEGFC expression robustly. Based on this finding, we tested the role of VEGFC in pathological retinal angiogenesis. VEGFC induced proliferation, migration, sprouting and tube formation of human retinal microvascular endothelial cells (HRMVECs) and these responses require CREB-mediated DLL4 expression and NOTCH1 activation. Furthermore, down regulation of VEGFC levels substantially reduced tip cell formation and retinal neovascularization in vivo. In addition, we observed that CREB via modulating the DLL4-NOTCH1 signaling mediates VEGFC induced tip cell formation and retinal neovascularization. In regard to upstream mechanism, we found that down regulation of p38beta levels inhibited hypoxia induced CREB-DLL4-NOTCH1 activation, tip cell formation, sprouting and retinal neovascularization. Based on these findings, it may be suggested that VEGFC besides its role in the regulation of lymphangiogenesis also plays a role in pathological retinal angiogenesis and this effect depends on p38beta and CREB mediated activation of DLL4-NOTCH1 signaling. PMID- 26870804 TI - A Pontine Region is a Neural Correlate of the Human Affective Processing Network. AB - The in vivo neural activity of the pons during the perception of affective stimuli has not been studied despite the strong implications of its role in affective processing. To examine the activity of the pons during the viewing of affective stimuli, and to verify its functional and structural connectivity with other affective neural correlates, a multimodal magnetic resonance imaging methodology was employed in this study. We observed the in vivo activity of the pons when viewing affective stimuli. Furthermore, small-world connectivity indicated that the functional connectivity (FC) between the pons and the cortico limbic affective regions was meaningful, with the coefficient lambda being positively associated with self-reported emotional reactivity. The FC between the pons and the cortico-limbic-striatal areas was related to self-reported negative affect. Corroborating this finding was the observation that the tract passing through the pons and the left hippocampus was negatively related to self-reported positive affect and positively correlated with emotional reactivity. Our findings support the framework that the pons works conjunctively with the distributed cortico-limbic-striatal systems in shaping individuals' affective states and reactivity. Our work paves the path for future research on the contribution of the pons to the precipitation and maintenance of affective disorders. PMID- 26870803 TI - Stress Granules Modulate SYK to Cause Microglial Cell Dysfunction in Alzheimer's Disease. AB - Microglial cells in the brains of Alzheimer's patients are known to be recruited to amyloid-beta (Abeta) plaques where they exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. In this study, we show that microglia stressed by exposure to sodium arsenite or Abeta(1-42) peptides or fibrils form extensive stress granules (SGs) to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of SGs, is active within the resulting SGs and stimulates the production of reactive oxygen and nitrogen species that are toxic to neuronal cells. This sequestration of SYK inhibits the ability of microglial cells to phagocytose Escherichia coli or Abeta fibrils. We find that aged microglial cells are more susceptible to the formation of SGs; and SGs containing SYK and phosphotyrosine are prevalent in the brains of patients with severe Alzheimer's disease. Phagocytic activity can be restored to stressed microglial cells by treatment with IgG, suggesting a mechanism to explain the therapeutic efficacy of intravenous IgG. These studies describe a mechanism by which stress, including exposure to Abeta, compromises the function of microglial cells in Alzheimer's disease and suggest approaches to restore activity to dysfunctional microglial cells. PMID- 26870806 TI - A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance). AB - BACKGROUND: Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely. METHODS: This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray(r) platform for TaqMan(r) RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature. FINDINGS: Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity. CONCLUSIONS: A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC. PMID- 26870807 TI - Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells. AB - BACKGROUND: CTCs provide prognostic information and their application is under investigation in multiple tumor types. Of the multiple variables inherent in any such process, none is more important to outcome than the appropriateness of the sample source. To address this question, we investigated CTCs in paired peripheral venous and arterial blood specimens obtained from stage IV uveal melanoma patients. METHODS: Blood specimens were obtained from both common femoral arteries and antecubital veins in 17 uveal melanoma patients with multiple hepatic metastases for CTC measurements. FINDING: CTCs were detectable with greater frequency (100%) and in larger numbers (median 5, range 1 to 168) in all arterial blood specimens than in venous samples (52.9%; median 1, range 0 to 8). Patients with hepatic as well as extra-hepatic metastasis showed higher number of arterial CTCs, compared to patients with liver-only metastasis (p = 0.003). There was no significant association between the number of arterial CTCs and the tumor burden within the liver in patients who had liver-only metastases. INTERPRETATION: Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs. PMID- 26870805 TI - The Sigma-2 Receptor and Progesterone Receptor Membrane Component 1 are Different Binding Sites Derived From Independent Genes. AB - The sigma-2 receptor (S2R) is a potential therapeutic target for cancer and neuronal diseases. However, the identity of the S2R has remained a matter of debate. Historically, the S2R has been defined as (1) a binding site with high affinity to 1,3-di-o-tolylguanidine (DTG) and haloperidol but not to the selective sigma-1 receptor ligand (+)-pentazocine, and (2) a protein of 18-21 kDa, as shown by specific photolabeling with [(3)H]-Azido-DTG and [(125)I] iodoazido-fenpropimorph ([(125)I]-IAF). Recently, the progesterone receptor membrane component 1 (PGRMC1), a 25 kDa protein, was reported to be the S2R (Nature Communications, 2011, 2:380). To confirm this identification, we created PGRMC1 knockout NSC34 cell lines using the CRISPR/Cas9 technology. We found that in NSC34 cells devoid of or overexpressing PGRMC1, the maximum [(3)H]-DTG binding to the S2R (Bmax) as well as the DTG-protectable [(125)I]-IAF photolabeling of the S2R were similar to those of wild-type control cells. Furthermore, the affinities of DTG and haloperidol for PGRMC1 (KI = 472 MUM and 350 MUM, respectively), as determined in competition with [(3)H]-progesterone, were more than 3 orders of magnitude lower than those reported for the S2R (20-80 nM). These results clarify that PGRMC1 and the S2R are distinct binding sites expressed by different genes. PMID- 26870809 TI - Erratum to "Efficacy of Adjunctive Tofacitinib Therapy in Mouse Models of Tuberculosis" [EBioMedicine 2 (8), August 2015, 868-873]. PMID- 26870808 TI - Prediction of Cancer Prevention: From Mammogram Screening to Identification of BRCA1/2 Mutation Carriers in Underserved Populations. AB - BACKGROUND: The US Preventative Service Task Force recommends that physicians perform a genetic risk assessment to identify women at risk for BRCA1/2 mutations associated with hereditary breast and ovarian cancer (HBOC) syndrome. However, outcomes data after a diagnosis of HBOC syndrome especially in diverse populations, are minimal. Here we asked if genetic screening of high-risk underserved women identified in the mammogram population reduces cancer incidence. METHODS: We evaluated 61,924 underserved women at screening mammography for family histories suggestive of HBOC syndrome over the course of 21 months. Data were collected retrospectively from patients at two safety net hospitals through chart review. A computer model was used to calculate the long term effect of this screening on cancer incidence by assessing both the mutation detection rate and the completion of prophylactic surgeries in BRCA1/2 mutation carriers. FINDINGS: We identified 20 of the 85 (23.5%) expected BRCA1/2 mutation carriers in the underserved population. The frequencies of prophylactic mastectomies and oophorectomies in the mutation carriers were 25% and 40%, respectively. Using these data, our model predicted only an 8.8% reduction in both breast and ovarian cancer in the underserved patients. This contrasts with a 57% reduction in breast cancer and 51% reduction in ovarian cancer in an insured reference population. Our data indicate that underserved patients with HBOC syndrome are difficult to identify and when identified are limited in their ability to adhere to NCCN guidelines for cancer prevention. INTERPRETATION: Screening for women at risk for HBOC syndrome in mammogram populations will only prevent cancers if we can increase compliance with management guidelines. This study provides prototypic baseline data for step-wise analysis of the efficacy of the use of family history analysis in the mammography setting for detection and management of HBOC syndrome. PMID- 26870810 TI - Towards a Biopsychosocial Model of Gulf War Illness? PMID- 26870811 TI - Localization of Viral Antigens Improves Understanding of Congenital Rubella Syndrome Pathophysiology. PMID- 26870812 TI - Plasma Biomarkers of HIV-associated Cognitive Disease. PMID- 26870813 TI - Thiamine Metabolites and Dementia? PMID- 26870814 TI - Allergy Associations with the Adult Fecal Microbiota: Cause, Effect or Biomarker? PMID- 26870816 TI - Human Leukemic Cells performing Oxidative Phosphorylation (OXPHOS) Generate an Antioxidant Response Independently of Reactive Oxygen species (ROS) Production. AB - Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS) generate reactive oxygen species (ROS) through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE), e.g. the genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 and releases NRF2, which activates AREs. We show in vitro and in vivo that OXPHOS induces, both in primary leukemic cells and cell lines, de novo expression of NQO-1 and HO-1 and also the MAPK ERK5 and decreases KEAP1 mRNA. ERK5 activates the transcription factor MEF2, which binds to the promoter of the miR-23a-27a-24-2 cluster. Newly generated miR 23a destabilizes KEAP1 mRNA by binding to its 3'UTR. Lower KEAP1 levels increase the basal expression of the NRF2-dependent genes NQO-1 and HO-1. Hence, leukemic cells performing OXPHOS, independently of de novo ROS production, generate an antioxidant response to protect themselves from ROS. PMID- 26870815 TI - Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma. AB - Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors. PMID- 26870817 TI - P-glycoprotein Mediates Ceritinib Resistance in Anaplastic Lymphoma Kinase rearranged Non-small Cell Lung Cancer. AB - The anaplastic lymphoma kinase (ALK) fusion oncogene is observed in 3%-5% of non small cell lung cancer (NSCLC). Crizotinib and ceritinib, a next-generation ALK tyrosine kinase inhibitor (TKI) active against crizotinib-refractory patients, are clinically available for the treatment of ALK-rearranged NSCLC patients, and multiple next-generation ALK-TKIs are currently under clinical evaluation. These ALK-TKIs exhibit robust clinical activity in ALK-rearranged NSCLC patients; however, the emergence of ALK-TKI resistance restricts the therapeutic effect. To date, various secondary mutations or bypass pathway activation-mediated resistance have been identified, but large parts of the resistance mechanism are yet to be identified. Here, we report the discovery of p-glycoprotein (P gp/ABCB1) overexpression as a ceritinib resistance mechanism in ALK-rearranged NSCLC patients. P-gp exported ceritinib and its overexpression conferred ceritinib and crizotinib resistance, but not to PF-06463922 or alectinib, which are next-generation ALK inhibitors. Knockdown of ABCB1 or P-gp inhibitors sensitizes the patient-derived cancer cells to ceritinib, in vitro and in vivo. P gp overexpression was identified in three out of 11 cases with in ALK-rearranged crizotinib or ceritinib resistant NSCLC patients. Our study suggests that alectinib, PF-06463922, or P-gp inhibitor with ceritinib could overcome the ceritinib or crizotinib resistance mediated by P-gp overexpression. PMID- 26870819 TI - Reduced Human Leukocyte Antigen (HLA) Protection in Gulf War Illness (GWI). AB - BACKGROUND: Gulf War Illness (GWI) is a disease of unknown etiology with symptoms suggesting the involvement of an immune process. Here we tested the hypothesis that Human Leukocyte Antigen (HLA) composition might differ between veterans with and without GWI. METHODS: We identified 144 unique alleles of Class I and II HLA genes in 82 veterans (66 with and 16 without GWI). We tested the hypothesis that a subset of HLA alleles may classify veterans in their respective group using a stepwise linear discriminant analysis. In addition, each participant rated symptom severity in 6 domains according to established GWI criteria, and an overall symptom severity was calculated. FINDINGS: We found 6 Class II alleles that classified participants 84.1% correctly (13/16 control and 56/66 GWI). The number of copies of the 6 alleles was significantly higher in the control group, suggesting a protective role. This was supported by a significant negative dependence of overall symptom severity on the number of allele copies, such that symptom severity was lower in participants with larger numbers of allele copies. INTERPRETATION: These results indicate a reduced HLA protection (i.e. genetic susceptibility) in veterans with GWI. FUNDING: University of Minnesota and U.S. Department of Veterans Affairs. PMID- 26870818 TI - Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity. AB - Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naive animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development. PMID- 26870820 TI - Immunolocalization and Distribution of Rubella Antigen in Fatal Congenital Rubella Syndrome. AB - BACKGROUND: An estimated 100,000 cases of congenital rubella syndrome (CRS) occur worldwide each year. The reported mortality rate for infants with CRS is up to 33%. The cellular mechanisms responsible for the multiple congenital defects in CRS are presently unknown. Here we identify cell types positive for rubella virus (RV) in CRS infants. METHODS: Cells and organs involved in RV replication were identified in paraffin-embedded autopsy tissues from three fatal case-patients by histopathologic examination and immunohistochemical (IHC) staining using a rabbit polyclonal RV antibody. Normal rabbit antisera and RV antisera preabsorbed with highly purified RV served as negative controls. RESULTS: RV antigen was found in interstitial fibroblasts in the heart, adventitial fibroblasts of large blood vessels, alveolar macrophages, progenitor cells of the outer granular layer of the brain, and in capillary endothelium and basal plate in the placenta. The antibody specificity was verified by IHC staining of multiple tissue sections from other infectious disease cases. RV infection of each cell type is consistent with abnormalities which have been identified in patients with CRS, in the heart, large blood vessels, and brain. Antigen distribution was consistent with inflammatory response to vascular injury and systemic spread of RV. CONCLUSIONS: The identification of RV positive cell types in CRS is important to better understand the pathology and pathogenesis of CRS. PMID- 26870821 TI - Genetic Variation in NFKBIE Is Associated With Increased Risk of Pneumococcal Meningitis in Children. AB - BACKGROUND: Streptococcus pneumoniae and Neisseria meningitidis are frequent pathogens in life-threatening infections. Genetic variation in the immune system may predispose to these infections. Nuclear factor-kappaB is a key component of the TLR-pathway, controlled by inhibitors, encoded by the genes NFKBIA, NFKBIE and NFKBIZ. We aimed to replicate previous findings of genetic variation associated with invasive pneumococcal disease (IPD), and to assess whether similar associations could be found in invasive meningococcal disease (IMD). METHODS: Cases with IPD and IMD and controls were identified by linking Danish national registries. DNA was obtained from the Danish Neonatal Screening Biobank. The association between SNPs and susceptibility to IPD and IMD, mortality and pneumococcal serotypes was investigated. RESULTS: 372 children with pneumococcal meningitis, 907 with pneumococcal bacteremia and 1273 controls were included. We included 406 cases with meningococcal meningitis, 272 with meningococcal bacteremia, and 672 controls. The NFKBIE SNP was associated with increased risk of pneumococcal meningitis (aOR 1.68; 95% CI: 1.20-2.36), but not bacteremia (aOR 1.08; 95% CI: 0.86-1.35). The remaining SNPs were not associated with susceptibility to invasive disease. None of the SNPs were associated with risk of IMD or mortality. CONCLUSIONS: A NFKBIE polymorphism was associated with increased risk of pneumococcal meningitis. PMID- 26870822 TI - Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal. AB - Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV 1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4 + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal. PMID- 26870824 TI - Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study. AB - BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. METHODS: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. FINDINGS: Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naive neuroasymptomatic subjects with low blood CD4(+) T cells. INTERPRETATION: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings. PMID- 26870823 TI - Small CD4 Mimetics Prevent HIV-1 Uninfected Bystander CD4 + T Cell Killing Mediated by Antibody-dependent Cell-mediated Cytotoxicity. AB - Human immunodeficiency virus type 1 (HIV-1) infection causes a progressive depletion of CD4 + T cells. Despite its importance for HIV-1 pathogenesis, the precise mechanisms underlying CD4 + T-cell depletion remain incompletely understood. Here we make the surprising observation that antibody-dependent cell mediated cytotoxicity (ADCC) mediates the death of uninfected bystander CD4 + T cells in cultures of HIV-1-infected cells. While HIV-1-infected cells are protected from ADCC by the action of the viral Vpu and Nef proteins, uninfected bystander CD4 + T cells bind gp120 shed from productively infected cells and are efficiently recognized by ADCC-mediating antibodies. Thus, gp120 shedding represents a viral mechanism to divert ADCC responses towards uninfected bystander CD4 + T cells. Importantly, CD4-mimetic molecules redirect ADCC responses from uninfected bystander cells to HIV-1-infected cells; therefore, CD4 mimetic compounds might have therapeutic utility in new strategies aimed at specifically eliminating HIV-1-infected cells. PMID- 26870825 TI - Hypothermic Preconditioning Reverses Tau Ontogenesis in Human Cortical Neurons and is Mimicked by Protein Phosphatase 2A Inhibition. AB - Hypothermia is potently neuroprotective, but the molecular basis of this effect remains obscure. Changes in neuronal tau protein are of interest, since tau becomes hyperphosphorylated in injury-resistant, hypothermic brains. Noting inter species differences in tau isoforms, we have used functional cortical neurons differentiated from human pluripotent stem cells (hCNs) to interrogate tau modulation during hypothermic preconditioning at clinically-relevant temperatures. Key tau developmental transitions (phosphorylation status and splicing shift) are recapitulated during hCN differentiation and subsequently reversed by mild (32 degrees C) to moderate (28 degrees C) cooling--conditions which reduce oxidative and excitotoxic stress-mediated injury in hCNs. Blocking a major tau kinase decreases hCN tau phosphorylation and abrogates hypothermic neuroprotection, whilst inhibition of protein phosphatase 2A mimics cooling induced tau hyperphosphorylation and protects normothermic hCNs from oxidative stress. These findings indicate a possible role for phospho-tau in hypothermic preconditioning, and suggest that cooling drives human tau towards an earlier ontogenic phenotype whilst increasing neuronal resilience to common neurotoxic insults. This work provides a critical step forward in understanding how we might exploit the neuroprotective benefits of cooling without cooling patients. PMID- 26870826 TI - Measurement of Blood Thiamine Metabolites for Alzheimer's Disease Diagnosis. AB - BACKGROUND: Brain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD). AIMS: To explore the diagnostic value of the measurement of blood thiamine metabolites for AD. METHODS: Blood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable gamma that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients. RESULTS: TDP and the gamma exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The gamma had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the gamma can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for gamma) and frontotemporal dementia (84.6% for TDP, 100.0% for gamma). Interpretation. The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits. PMID- 26870827 TI - A Single-blinded, Randomized Clinical Trial of How to Implement an Evidence-based Treatment for Generalized Anxiety Disorder [IMPLEMENT]--Effects of Three Different Strategies of Implementation. AB - BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF. PMID- 26870830 TI - Engineering Viruses to Fight Cancer. PMID- 26870828 TI - Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project. AB - BACKGROUND: Alteration of the gut microbial population (dysbiosis) may increase the risk for allergies and other conditions. This study sought to clarify the relationship of dysbiosis with allergies in adults. METHODS: Publicly available American Gut Project questionnaire and fecal 16S rRNA sequence data were analyzed. Fecal microbiota richness (number of observed species) and composition (UniFrac) were used to compare adults with versus without allergy to foods (peanuts, tree nuts, shellfish, other) and non-foods (drug, bee sting, dander, asthma, seasonal, eczema). Logistic and Poisson regression models adjusted for potential confounders. Odds ratios and 95% confidence intervals (CI) were calculated for lowest vs highest richness tertile. Taxonomy associations considered 122 non-redundant taxa (of 2379 total taxa) with >= 0.1% mean abundance. RESULTS: Self-reported allergy prevalence among the 1879 participants (mean age, 45.5 years; 46.9% male) was 81.5%, ranging from 2.5% for peanuts to 40.5% for seasonal. Fecal microbiota richness was markedly lower with total allergies (P = 10(-9)) and five particular allergies (P <= 10(-4)). Richness odds ratios were 1.7 (CI 1.3-2.2) with seasonal, 1.8 (CI 1.3-2.5) with drug, and 7.8 (CI 2.3-26.5) with peanut allergy. These allergic participants also had markedly altered microbial community composition (unweighted UniFrac, P = 10(-4) to 10( 7)). Total food and non-food allergies were significantly associated with 7 and 9 altered taxa, respectively. The dysbiosis was most marked with nut and seasonal allergies, driven by higher Bacteroidales and reduced Clostridiales taxa. INTERPRETATION: American adults with allergies, especially to nuts and seasonal pollen, have low diversity, reduced Clostridiales, and increased Bacteroidales in their gut microbiota. This dysbiosis might be targeted to improve treatment or prevention of allergy. PMID- 26870829 TI - Research Investments in Global Health: A Systematic Analysis of UK Infectious Disease Research Funding and Global Health Metrics, 1997-2013. AB - BACKGROUND: Infectious diseases account for a significant global burden of disease and substantial investment in research and development. This paper presents a systematic assessment of research investments awarded to UK institutions and global health metrics assessing disease burden. METHODS: We systematically sourced research funding data awarded from public and philanthropic organisations between 1997 and 2013. We screened awards for relevance to infection and categorised data by type of science, disease area and specific pathogen. Investments were compared with mortality, disability-adjusted life years (DALYs) and years lived with disability (YLD) across three time points. FINDINGS: Between 1997-2013, there were 7398 awards with a total investment of L3.7 billion. An increase in research funding across 2011-2013 was observed for most disease areas, with notable exceptions being sexually transmitted infections and sepsis research where funding decreased. Most funding remains for pre-clinical research (L2.2 billion, 59.4%). Relative to global mortality, DALYs and YLDs, acute hepatitis C, leishmaniasis and African trypanosomiasis received comparatively high levels of funding. Pneumonia, shigellosis, pertussis, cholera and syphilis were poorly funded across all health metrics. Tuberculosis (TB) consistently attracts relatively less funding than HIV and malaria. INTERPRETATION: Most infections have received increases in research investment, alongside decreases in global burden of disease in 2013. The UK demonstrates research strengths in some neglected tropical diseases such as African trypanosomiasis and leishmaniasis, but syphilis, cholera, shigellosis and pneumonia remain poorly funded relative to their global burden. Acute hepatitis C appears well funded but the figures do not adequately take into account projected future chronic burdens for this condition. These findings can help to inform global policymakers on resource allocation for research investment. PMID- 26870831 TI - From Ultrasonography to High Resolution Magnetic Resonance Imaging: Towards an Optimal Management Strategy for Vulnerable Carotid Atherosclerotic Plaques. PMID- 26870832 TI - Keep Harm at Bay: Oxidative Phosphorylation Induces Nrf2-Driven Antioxidant Response Via ERK5/MEF2/miR-23a Signaling to Keap-1. PMID- 26870833 TI - The Yin and Yang of ADCC-Mediating Antibodies. PMID- 26870835 TI - A new approach to predict soil temperature under vegetated surfaces. AB - In this article, the setup and the application of an empirical model, based on Newton's law of cooling, capable to predict daily mean soil temperature (Tsoil) under vegetated surfaces, is described. The only input variable, necessary to run the model, is a time series of daily mean air temperature. The simulator employs 9 empirical parameters, which were estimated by inverse modeling. The model, which primarily addresses forested sites, incorporates the effect of snow cover and soil freezing on soil temperature. The model was applied to several temperate forest sites, managing the split between Central Europe (Austria) and the United States (Harvard Forest, Massachusetts; Hubbard Brook, New Hampshire), aiming to cover a broad range of site characteristics. Investigated stands differ fundamentally in stand composition, elevation, exposition, annual mean temperature, precipitation regime, as well as in the duration of winter snow cover. At last, to explore the limits of the formulation, the simulator was applied to non-forest sites (Illinois), where soil temperature was recorded under short cut grass. The model was parameterized, specifically to site and measurement depth. After calibration of the model, an evaluation was performed, using ~50 % of the available data. In each case, the simulator was capable to deliver a feasible prediction of soil temperature in the validation time interval. To evaluate the practical suitability of the simulator, the minimum amount of soil temperature point measurements, necessary to yield expedient model performance was determined. In the investigated case 13-20 point observations, uniformly distributed within an 11-year timeframe, have been proven sufficient to yield sound model performance (root mean square error <0.9 degrees C, Nash Sutcliffe efficiency >0.97). This makes the model suitable for the application on sites, where the information on soil temperature is discontinuous or scarce. PMID- 26870834 TI - Evolving Therapeutic Strategies for the Classic Philadelphia-Negative Myeloproliferative Neoplasms. AB - Despite the emergence of JAK inhibitors, there is a need for disease-modifying treatments for Philadelphia-negative myeloproliferative neoplasms (MPNs). JAK inhibitors ameliorate symptoms and address splenomegaly, but because of the heterogeneous contributors to the disease process, JAK inhibitor monotherapy incompletely addresses the burden of disease. The ever-growing understanding of MPN pathogenesis has provided the rationale for testing novel and targeted therapeutic agents, as monotherapies or in combination, in preclinical and clinical settings. A number of intriguing options have emerged, and it is hoped that further progress will lead to significant changes in the natural history of MPNs. PMID- 26870837 TI - Clinical Clarity versus Terminological Order - The Readiness of SNOMED CT Concept Descriptors for Primary Care. AB - As SNOMED usage becomes more ingrained within applications, its range of concept descriptors, and particularly its synonym adequacy, becomes more important. A simulated clinical scenario involving various term-based concept searches is used to assess whether SNOMED's concept descriptors provide sufficient differentiation to enable possible concept selection between similar terms. Four random samples from different SNOMED concept populations are utilized. Of particular interest are concepts mapped duplicately into UMLS concepts due to shared term patterns. While overall synonym problems are rare (1%), some concept populations exhibited a high rate of potential problems for clinical use (17-62%). The vast majority of issues are due to SNOMED's inherent structure and fine granularity. Many findings hint at a lack of clear delineation between reference and interface terminological qualities. Closer attention should be given to practical clinical use-case scenarios. Reducing SNOMED's structural complexity may alleviate many of the described findings and encourage clinical adoption. PMID- 26870838 TI - New therapies for antiemetic prophylaxis for chemotherapy. AB - A number of new advances have occurred over the past 2 years in the management of chemotherapy-related nausea and vomiting (CINV). A new neurokinin-1 receptor antagonist (NK1RA), netupitant, has been combined with palonosetron in a single oral tablet for treating the effects of moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC). Rolapitant, another NK1RA, unlike aprepitant, has a long half-life and does not block CYP-3A4 and therefore has fewer drug interactions. Olanzapine reduces nausea more effectively than aprepitant in patients who are receiving HEC and is a better rescue antiemetic than is metoclopramide. Ginger lacks efficacy as an antiemetic agent for CINV. Although there was some evidence in a pilot study of gabapentin as an antiemetic, it was no better in reducing CINV than was placebo. Compliance to guidelines in multiple settings ranges from 50%-60% but is improved by computerized order entry of antiemetics and recommendations displayed with chemotherapy. PMID- 26870839 TI - Management of epidermal growth factor receptor inhibitor-associated rash: a systematic review. AB - Cancer patients treated with epidermal growth factor receptor inhibitors (EGFRIs) frequently experience skin toxicities (rash) that can compromise their quality of life and lead to dose reduction or discontinuation of treatment. Reflecting the need for effective management of EGFRI-associated rash, a number of clinical practice guidelines and management recommendations have been developed. The objective of this systematic review is to identify and summarize all available published recommendations of rash management strategies and evaluate their basis of evidence, to describe consensus in the recommendations, and where there is a lack of consensus to describe the opportunities for future clinical research to improve clinical practice in the management of EGFRI rash. Fifty-nine articles published from 2005-2011 were selected for inclusion in the systematic review. Common drug recommendations were oral and topical antibiotics, topical corticosteroids, and antihistamines; low-grade rash was generally recommended to be managed with topical antibiotics or corticosteroids, grade 2 rash with oral antibiotics or antihistamines, and severe grades of rash with oral corticosteroids or delay/dose reduction of EGFRI. The focus of clinical practice guidelines and recommendations was on reactive management. A better understanding of pre-emptive versus reactive treatment with the implementation of appropriately designed randomized controlled studies could support a more effective management of EGFRI-associated rash and improve patient outcomes. Consideration of patients' self-reported outcomes and consistent grading of rash toxicity are also recommended. Funding/sponsor: Eli Lilly & Co, Bristol-Myers Squibb. PMID- 26870836 TI - Collateral Lethality: A new therapeutic strategy in oncology. AB - Genomic deletion of tumor suppressor genes (TSG) is a rite of passage for virtually all human cancers. The synthetic lethal paradigm has provided a framework for the development of molecular targeted therapeutics that are functionally linked to the loss of specific TSG functions. In the course of genomic events that delete TSGs, a large number of genes with no apparent direct role in tumor promotion also sustain deletion as a result of chromosomal proximity to the target TSG. In this perspective, we review the novel concept of "collateral lethality", which has served to identify cancer-specific therapeutic vulnerabilities resulting from co-deletion of passenger genes neighboring TSG. The large number of collaterally deleted genes, playing diverse functions in cell homeostasis, offers a rich repertoire of pharmacologically targetable vulnerabilities presenting novel opportunities for the development of personalized anti-neoplastic therapies. PMID- 26870840 TI - Cyclical hypofractionated radiotherapy technique for palliative treatment of locally advanced head and neck cancer: institutional experience and review of palliative regimens. AB - BACKGROUND: Effective palliation in patients with locally advanced head and neck cancer is important. Cyclical hypofractionated radiotherapy (Quad Shot) is a short-course palliative regimen with good patient compliance, low rates of acute toxicity, and delayed late fibrosis. OBJECTIVE: To review use of the Quad Shot technique at our institution in order to quantify the palliative response in locally advanced head and neck cancer. METHODS: The medical records of 70 patients with head and neck squamous cell carcinoma who had been treated with the Quad Shot technique were analyzed retrospectively (36 had been treated with intensity-modulated radiation therapy and 34 with 3-D conformal radiotherapy). They had received cyclical hypofractionated radiotherapy administrated as 14.8 Gy in 4 fractions over 2 days, twice daily, repeated every 3 weeks for a total of 3 cycles. The total prescribed dose was 44.4 Gy. Primary endpoints were improvement in pain using a verbal numeric pain rating scale (range 1-10, 10 being severe pain) and dysphagia using the Food Intake Level Scale, and the secondary endpoints included overall survival (OS), local regional recurrence-free survival (LRRFS), progression-free survival (PFS) and time to progression. RESULTS: Pain response occurred in 61% of the patients. The mean pain scores decreased significantly from pre to post treatment (5.81 to 2.55, ?? = .009). The mean initial dysphagia score improved from 2.20 to 4.77 55 (?? = .045). 26% of patients developed mucositis (<= grade 2), with 9% developing grade 3-level mucositis. 12 patients had tumor recurrence. The estimated 1-year PFS was 20.7%. The median survival was 3.85 months with an estimated 1-year OS of 22.6%. Pain response (hazard ratio [HR], 2.69; 95% confidence index [CI], I.552-1.77) and completion of all 3 cycles (HR, 1.71; 95% CI, 1.003-2.907) were predictive for improved OS. LIMITATIONS: This study is a retrospective analysis. CONCLUSION: Quad Shot is an appropriate palliative regimen for locally advanced head and neck cancer. PMID- 26870841 TI - Impact of surgery for stage IA non-small-cell lung cancer on patient quality of life. AB - BACKGROUND: There is a paucity of literature comparing quality of life (QoL) before and after surgery in stage IA lung cancer, where surgical resection is the recommended curative treatment. OBJECTIVE: To assess the impact of surgery on physical and mental health-related QoL in patients with stage IA lung cancer treated with surgical resection. METHODS: Participants in the I-ELCAP cohort who were diagnosed with their first primary pathologic stage IA non-small-cell lung cancer, underwent surgery, and provided follow-up information on QoL 1 year later were included in the present analysis (N = 107). QoL information was collected using the SF-12 (12-item Short Form Health Survey), which generates 2 component scores related to mental health and physical health. RESULTS: Statistical analyses indicated that physical health QoL was significantly worsened from before surgery to after surgery, whereas mental health QoL marginally improved from before to after surgery. Physical health QoL worsened for women from baseline to follow-up, but not for men. Only lobectomy (not limited resection) had an impact on QoL from before to after surgery. LIMITATIONS: Results are considered preliminary given the small sample size and multiple comparisons. CONCLUSIONS: The current study findings have implications for lung cancer health care professionals in regard to how they can most effectively present the possible impact of surgery on quality of life to this subset of patients in which disease has not yet significantly progressed. PMID- 26870842 TI - Thyroid nodule: not as clear-cut as it seems. AB - Benign etiologies and primary thyroid cancers are the most common causes of incidental thyroid nodules. Clinically evident metastases to the thyroid gland are not common and account for 2%-3% of thyroid cancers, though the incidence of thyroid metastases reaches 24% in autopsy studies.1 The most common clinically detected thyroid metastases originate from renal cell carcinoma (RCC; 48.1%).2 We report here a rare case of a man with clear-cell RCC with late recurrence in the thyroid gland as a solitary metastasis, 13 years after the primary diagnosis. The patient received neo-adjuvant targeted therapy with sunitinib, then underwent thyroidectomy. The surgical margins were positive, and the patient had adjuvant radiation therapy. He is currently on long-term surveillance. PMID- 26870843 TI - Periodontal Dressing as an Adjunct after Scaling and Root Planing--A Useful Preventive Tool? AB - PURPOSE: To determine the preventive effect of a periodontal dressing containing colophony, zinc oxide and magnesium oxide applied after scaling and root planing on clinical variables, subgingival bacteria and local immune response in patients with chronic periodontitis. MATERIALS AND METHODS: In this randomised prospective clinical study, 28 volunteers with generalised moderate chronic periodontitis were treated with full-mouth scaling in a split-mouth design. In the test quadrants, the periodontal dressing was applied during the first three days. At baseline and after 6 and 12 weeks, probing pocket depth (PD), attachment level (AL) and bleeding on probing (BOP) were recorded, and subgingival plaque samples were taken for laboratory analysis. RESULTS: In both groups, PD, AL and BOP were significantly reduced (p=0.001). BOP was significantly lower in the control than the test group after 6 weeks (p=0.046). Significantly reduced bacterial counts of Porphyromonas gingivalis were found in the control group after 12 weeks (p=0.013). No differences were found for the microbiological results between the groups. After 12 weeks, interleukin (IL)-8 and matrix metalloproteinase (MMP)-8 were significantly higher in the test group (p=0.023 and p=0.003, respectively). CONCLUSION: The adjunctive application of a periodontal dressing had no additional preventive effect on clinical data 12 weeks after scaling and root planing. PMID- 26870844 TI - Association of Oral Health-related Quality of Life with Periodontal Status and Treatment Needs. AB - PURPOSE: To evaluate the association of oral health-related quality of life (OHRQoL) with periodontal parameters and treatment needs in a Turkish population and compare the OHRQoL of patients with gingivitis and periodontitis. MATERIALS AND METHODS: The present study had a cross-sectional design. The study population consisted of 404 patients with periodontitis (n = 130), gingivitis (n = 141) or periodontal health (n = 133). Patients' sociodemographic information as well as periodontal parameters such as plaque index (PI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL) and the community periodontal index of treatment needs were recorded. The impact of oral health on the patients' quality of life was assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire. RESULTS: The OHIP-14 scores in subjects with gingivitis and periodontitis were higher than in periodontally healthy individuals (p < 0.05). Although the total OHIP-14 scores in subjects with periodontitis were higher than those for the subjects with gingivitis, no statistically significant difference existed between the gingivitis and periodontitis groups (p > 0.05). When characterised according to periodontal treatment needs (TN), the total and individual domain OHIP-14 scores were highest in subjects at the TN3 level. The total OHIP-14 scores of subjects correlated with periodontal status, BOP, PD >= 4 mm (% of sites), CAL >= 4 mm (% of sites) and TN. CONCLUSIONS: Our results disclosed that the adverse effects on OHRQoL perceived by patients were similar in subjects with gingivitis and periodontitis. When planning treatment, it should be kept in mind that the pain and physical discomfort domains of the individual subscales are of primary importance to the patients. However, longitudinal studies are needed to clarify the relationship between periodontal status and OHRQoL. PMID- 26870846 TI - Effect of an Educational Programme on the Knowledge Level Among an Emergency Service Medical Team Regarding Tooth Avulsion. AB - PURPOSE: To evaluate the effectiveness of an educational intervention in improving the level of knowledge of tooth avulsion among non-dental healthcare professionals of an emergency medical service in Brazil and the maintenance of this knowledge after a 6-month period. MATERIALS AND METHODS: An intervention study was carried out involving the administration of a questionnaire and presentation of a lecture to 73 healthcare professionals (11 physicians, 41 nurses and 21 paramedics) of an emergency medical service in Brazil. The questionnaire was administered before (T0), immediately after (T1) and 6 months after the lecture (T2). McNemar's test was used to compare the responses, with the significance level set at 5% (p < 0.05). RESULTS: A general improvement was found regarding the concept of tooth avulsion, replantation, conduct in cases of avulsion, ideal time for replantation, ability to perform replantation and storage medium prior to replantation between baseline (T0) and the post-lecture evaluations (p < 0.05). However, an increase in insecurity regarding replantation was found between T1 and T2 (p < 0.001). CONCLUSION: The educational intervention led to a significant increase in the number of correct answers regarding the measures to be taken in cases of tooth avulsion. The professionals' knowledge level remained high 6 months after the lecture. However, a certain degree of insecurity was found regarding the ability to perform replantation. PMID- 26870845 TI - Racial and Ethnic Differences in Self-Reported Periodontal Disease in the Multi Ethnic Study of Atherosclerosis (MESA). AB - PURPOSE: Racial and ethnic disparities in periodontal disease exist in the United States. This study examined the prevalence of self-reported periodontal disease, and the extent to which racial/ethnic disparities in the reported disease were reduced or eliminated after controlling for various risk factors in a multi ethnic study population of older adults. MATERIALS AND METHODS: Information from the baseline examination (July 2000-August 2002) of the Multi-Ethnic Study of Atherosclerosis (MESA) was used. Study participants (N = 6256) were age 45-84 years and identified themselves as either: white, black, Hispanic or Chinese. Periodontal disease was assessed by self-report; demographic and socioeconomic status (SES) indicators, biomedical risk factors and psychosocial stress factors were used as predictors of self-reported periodontal disease. RESULTS: Chinese displayed the highest prevalence of self-reported periodontal disease (39.8%), followed by blacks (32.0%) and whites (26.0%), with Hispanics displaying the lowest prevalence (17.4%). Chinese and black participants had a significantly higher prevalence of disease compared to whites that persisted after adjusting for demographic and SES indicators, biomedical risk factors and psychosocial stress factors. After such adjustment, Hispanics did not differ significantly from whites in their reporting of disease. CONCLUSION: Racial/ethnic disparities in self-reported periodontal disease persisted after adjusting for all study covariates. This study highlights the need for continued research into the determinants of racial/ethnic disparities in periodontal disease in order to better target interventions aimed at reducing the burden of disease in all segments of the U.S. population. PMID- 26870847 TI - Are Carious Lesions in Previously Sealed Occlusal Surfaces Detected as well on Colour Photographs as by Visual Clinical Examination? AB - PURPOSE: To compare the level of agreement between carious lesion assessments according to the visual clinical examination and the colour photograph methods. MATERIALS AND METHODS: Data on the presence of enamel/dentin carious lesions in previously sealed occlusal surfaces in first molars were obtained by two trained and calibrated examiners through visual clinical examination and from colour photographs 4 years after sealing. Kappa statistics were applied to calculate agreement between assessment methods. Data analysis was performed using sign, Bowker symmetry and McNemar's tests. RESULTS: The prevalence of dentin carious lesions was very low. The kappa coefficients for detecting enamel/dentin carious lesions using the two assessment methods were 0.65 (CI: 0.56-0.74) for examiner 1 and 0.70 (CI: 0.62-0.78) for examiner 2. Examiner 2 observed more enamel/dentin carious lesions on colour photographs than did examiner 1 (p = 0.008). Sensitivity analyses did not confirm this outcome. CONCLUSIONS: There was no difference in the detection of enamel/dentin carious lesions in previously sealed occlusal surfaces using colour photographs vs visual clinical examination. The colour photograph method is therefore equivalent to the visual clinical examination in detecting enamel/dentin carious lesions. More studies are required. PMID- 26870848 TI - Five-year Sealant Retention and Efficacy in a Multi-operated School-based Oral Health Programme in Kuwait. AB - PURPOSE: To evaluate sealant retention in a multi-operator school-based oral health programme and sealant efficacy in preventing caries in a high caries-risk population. MATERIALS AND METHODS: Sealant retention and caries status in previously placed sealants on permanent first molars were evaluated in 503 children ages 6 to 8 years at 20 primary schools. A total of 2538 sealants were applied on 876 first permanent molars and evaluated for retention and efficacy in preventing caries from 2002 to 2007. These sealants were placed on occlusal and buccal or palatal surfaces using a standard protocol after isolation with rubber dam or cotton roll. Caries was scored in teeth in which the sealants were partially or completely lost. RESULT: 1752 sealants (69%) were examined at the end of the fifth year, with 58.3% of the sealants completely retained, 7.4% partially lost, 19% completely lost, 6.2% resealed and 9.1% restored. Only 3.1% of the previously sealed teeth were carious and 87.8% of previously sealed teeth were caries free. In multivariate analysis, occlusal surfaces were 2.0 times more likely to retain a sealant than were the buccal and palatal pits (p < 0.0001). No differences in sealant retention vs caries by arch, or teeth isolated using rubber-dam vs cotton roll were seen. CONCLUSION: The present study shows the effectiveness of sealants in caries prevention in a multi-operator school sealant programme, and provides evidence supporting their use in such programmes for high caries populations. PMID- 26870849 TI - Microbiological Distribution of Six Periodontal Pathogens Between Untreated Italian and Dutch Periodontal Patients. AB - PURPOSE: To compare prevalence and microbial load of six periodontal pathogens between Italian and Dutch patients affected by chronic periodontitis, using oligonucleotide probe technology. MATERIALS AND METHODS: Subgingival plaque samples data from 352 Italians and 115 Dutch periodontal patients were analysed and compared. Bleeding on probing, suppuration, probing pocket depth, clinical attachment level, age, gender, ethnicities and smoking habits were recorded. Presence and level of bacterial species were determined by realtime polymerase chain reaction under the identical microbiological protocol. Statistical analysis was performed using the chi-square test, Mann-Whitney U-test and binary unconditional logistic regression (alpha = 0.05). RESULTS: Between populations, only Treponema denticola and Porphyromonas gingivalis differed significantly, being more prevalent in the Italian group (p = 0.0001). Except for Tannerella forsythia, all bacterial loads differed significantly: Treponema denticola (p = 0.0001) and Prevotella intermedia (p = 0.001) were higher in Italians, while Porphyromonas gingivalis (p = 0.001), Fusobacterium nucleatum (p = 0.03) and Aggregatibacter actinomycetemcomitans (p = 0.001) were higher in Dutch patients. CONCLUSIONS: Significant differences in prevalence and bacterial load of periodontal pathogens exist between Italian and Dutch patients affected by chronic periodontitis. The microbiological profile, and particularly the bacterial load of pathogens, varied significantly between populations. PMID- 26870850 TI - Prevalence and Predictors of Early Childhood Caries in 3- to 6-year-old South Indian Children--A Cross-sectional Descriptive Study. AB - PURPOSE: To determine the prevalence and potential risk factors of ECC in 3- to 6 year-old preschool children. MATERIALS AND METHODS: A sample of 477 preschool children aged 3 to 6 years was randomly selected from the schools in the area of study. Caries was recorded according to the WHO criteria from 1997. Information regarding demographic data, socioeconomic status, feeding habits, oral hygiene practices, birthweight and the children's visits to the dentist was obtained through a structured questionnaire. The data were analysed using Student's t test, the chi-square test and Pearson's correlation analysis. RESULTS: The prevalence of early childhood caries in 3- to 6-year-old preschool children was found to be 27.3% with a mean dmft of 2.36. ECC increased significantly with age and is more predominant in girls. The maxillary arch was more affected than mandibular arch and children belonging to the low socioeconomic group showed higher caries prevalence. ECC is more prevalent in children accustomed to on demand breast feeding, bottle feeding at night, between-meal snacking and sweetened pacifier use. Factors such as increased frequency of toothbrushing, use of toothbrush and fluoridated dentifrice were found to be the protective factors against the risk of ECC. CONCLUSION: A strong correlation between the risk factors studied and ECC was found. Health education, proper guidelines on feeding and oral hygiene practices and access to early oral health care can substantially reduce the risk and prevalence of ECC. PMID- 26870851 TI - Soda Consumption Among Methamphetamine Users in the USA: Impact on Oral Health. AB - PURPOSE: Dental disease is associated with methamphetamine (MA) use and partly attributed to excessive consumption of sugared sodas. Hence, the purpose of this study was to verify patterns of sugared soda intake and their relationship to oral health. MATERIALS AND METHODS: Detailed assessments with 541 MA users at two dental clinics were conducted. Assessment included a lifetime history of methamphetamine use, sugared soda consumption and a dental exam. RESULTS: Subjects were predominantly male (80.8%; mean age 44.4 years), on average had used MA for 11.6 years and drank an average of 35.3 sodas per month. Number of days of MA use over the past 30 days was significantly associated with soda consumption. Increased years of MA use was associated with the likelihood of users reporting less overall satisfaction with life because of their teeth, specifically difficulty eating, and dry mouth. This is the first study to show a statistically significant association between MA use and sugared soda consumption. CONCLUSIONS: MA users' consumption of sugared sodas is higher than in the adult general population, and this is the first study to show a statistically significant association between MA use and sugared soda consumption. In addition, increased soda consumption was associated with more dental problems among MA users. PMID- 26870852 TI - CAMBRA as a Tool for Caries Risk Prediction Among 12- to 13-year-old Institutionalised Children - A Longitudinal Follow-up Study. AB - PURPOSE: To evaluate CAMBRA (Caries Management by Risk Assessment) as a tool for caries risk prediction among 12- to 13-year-old institutionalised children and to validate it against the new increment of caries lesions. MATERIALS AND METHODS: A longitudinal follow-up study was conducted among 72 institutionalised children. Baseline data were collected in the month of August, 2011. Children were individually interviewed to record the nonclinical information necessary to complete the CAMBRA. Clinical information for the assessment of visible plaque was recorded using the Silness and Loe plaque index and evidence of decalcification and caries was recorded using ICDAS criteria. The children underwent the follow-up examination in August 2013 to determine the new increment of dental caries. RESULTS: 19.44% of the subjects were classified as low risk, 22.22% as moderate risk, and 58.33% as high risk for caries. The highest odds ratio (OR) for disease indicators was 7.31 for restorations in the last 3 years. The highest OR for pathological factors was 7.15 for mutans streptococci, followed by 5.54 for visible heavy plaque. The highest OR for protective factors was 0.56, i.e. a negative association of fluoride toothpaste. Among those subjects assessed as moderate and high risk for caries at baseline, 37.5% and 47.6%, respectively, had new cavities at the follow-up examination. Sensitivity for CAMBRA was found to be 47.62% with a specificity of 80%, and the area under the ROC curve was found to be 0.638. CONCLUSION: CAMBRA was valid and highly predictive in determining the caries risk among institutionalised children. PMID- 26870853 TI - Comparative Assessment of Oral Health Related Quality of Life in Chronic Periodontitis Patients of Rural and Urban Populations in Punjab. AB - PURPOSE: To assess and compare the oral health related quality of life in patients suffering from chronic periodontitis using the short questionnaire of oral health impact profile (OHIP-14) in rural and urban populations of Punjab state, India. MATERIALS AND METHODS: One hundred patients suffering from chronic periodontitis were screened and divided into two groups, rural and urban (50 participants in each group). The clinical parameters plaque index (PI), gingival index (GI), pocket probing depth (PPD) and OHIP-14 were assessed in all patients. RESULTS: The mean PI (2.11 +/- 0.635), GI (1.61 +/- 0.45), PPD (3.12 +/- 0.692) and OHIP-14 (11.49 +/- 9.733) scores were significantly higher in the rural than in the urban population (1.69 +/- 0.45, 1.56 +/- 0.355, 3.30 +/- 0.973, 5.88 +/- 5.588, respectively) suffering from chronic periodontitis. The most affected domain in the rural population was functional limitation, whereas psychological disability was the most affected in the urban population. A statistically significant positive correlation was observed between the periodontal parameters and OHIP-14 (p < 0.001) in both groups. CONCLUSION: Within the limitations of the study, periodontal status and oral health related quality of life are significantly correlated with each other in both rural and urban populations. PMID- 26870854 TI - beta-Cyclodextrin functionalized carbon quantum dots as sensors for determination of water-soluble C60 fullerenes in water. AB - A selective photoluminescence method based on Carbon Quantum Dots (CQDs) functionalized with carboxymethyl-beta-cyclodextrin for the direct determination of water-soluble C60 fullerene has been developed. CQDs were synthesized using a top-down methodology from multiwall carbon nanotubes (MWCNTs) and further functionalized with N-Boc-ethylenediamine to confer monoprotected amine groups onto their surface. Once amine-functionalized CQDs were obtained after deprotection, an amidation reaction with carboxymethyl-beta-cyclodextrin cavitands was achieved and the obtained fluorescent beta-cyclodextrin functionalized Carbon Quantum Dots (cd-CQDs) were investigated for the inclusion complexation of water-soluble C60. Quenching of their fluorescence was observed owing to the non-covalent self-assembly of cd-CQDs and C60, making possible the quantification of C60. A method to determine water-soluble C60 is then proposed with detection and quantification limits of 0.525 and 1.751 MUg mL(-1), respectively. The method was validated by determining soluble C60 fullerene in spiked river water. One added value of the paper is the fact that it can be ascribed to the "Third Way in Analytical Nanoscience and Nanotechnology". PMID- 26870856 TI - Preface. PMID- 26870855 TI - Surface modification of strontium-doped porous bioactive ceramic scaffolds via poly(DOPA) coating and immobilizing silk fibroin for excellent angiogenic and osteogenic properties. AB - For bioceramic scaffolds employed in clinical applications, excellent bioactivity and tenacity were of great importance. Modifying inorganic SCPP scaffolds with biological macromolecules could obviously improve its bioactivity and eliminate its palpable brittleness. However, it was hard to execute directly due to extremely bad interfacial compatibility between them. In this research, dopamine (DOPA) was introduced onto strontium-doped calcium polyphosphate (SCPP) scaffolds, subsequently the preliminary material was successfully further modified by silk fibroin (SF). SCPP/D/SF possessed suitable biomechanical properties, ability to stimulate angiogenic factor secretion and excellent biocompatibility. Biomechanical examination demonstrated that SCPP/D/SF scaffolds yielded better compressive strength because of improved interfacial compatibility. MTT assay and CLSM observation showed that SCPP/D/SF scaffolds had good cytocompatibility and presented better inducing-cell-migration potential than pure SCPP scaffolds. Meanwhile, its ability to stimulate angiogenic factor secretion was measured through the ELISA assay and immunohistological analysis in vitro and in vivo respectively. The results revealed, superior to SCPP, SCPP/D/SF could effectively promote VEGF and bFGF expression, possibly leading to enhancing angiogenesis and osteogenesis. In a word, SCPP/D/SF could serve as a potential bone tissue engineering scaffold for comparable biomechanical properties and excellent bioactivity. It provided a novel idea for modification of inorganic materials to prepare promising bone tissue engineering scaffolds with the ability to accelerate bone regeneration and vascularization. PMID- 26870858 TI - Cough and confusion in an elderly man with chronic lymphocytic leukemia. PMID- 26870859 TI - Placental abnormalities. Prenatally undiagnosed vasa previa. PMID- 26870857 TI - Matt Griffiths replies. PMID- 26870860 TI - Chest X-ray quiz. PMID- 26870861 TI - [Acute rheumatic fever and infectious-inflammatory diseases of the pharynx: the relationship, treatment, and prophylaxis]. AB - The relationship between pharyngeal infections, such as tonsillitis and pharyngitis, caused by group A beta-hemolytic streptococci (BHSA) and acute rheumatic fever (ARF) is a well-established fact confirmed by numerous studies carried out along the following lines: epidemiological, immunological, therapeutic, and prophylactic. The currently available data provide an opportunity to discuss the existence of "rheumatogenic" BHSA strains exhibiting a number of characteristic clinical and morphological properties. According to the current recommendations penicillins remain the means of first-line therapy for the treatment of acute forms of BHSA-induced tonsillitis and pharyngitis, whereas the macrolides should be applied only as the alternative medications in the patients with intolerance to beta-lactam antibiotics. This article contains characteristics of BHSA-carrier state and the principal indications for the prescription of antibiotics to the patients with these conditions. The key principle of secondary medicamental prophylaxis of acute respiratory infections are expounded along with the main fines of future research on the problems associated with BHSA-induced pharyngeal infections. PMID- 26870862 TI - [The modern strategy for the treatment of the patients presenting with odontogenic maxillary sinusitis and the oroantral fistula]. AB - The objective of the present study was the comparative analysis of various methods for the plastic correction of the oroantral fistula with the use of the mucosal flap and the osteoplastic materials based on the data from the literature and on-line publkations. The characteristics of an ideal material for the plastic correction ot the oroantral fistula and the conditions for carrying out this surgery are discussed. PMID- 26870863 TI - [Yakov Solomonivich Temkin. The vast mind and the kind heart]. PMID- 26870864 TI - A Tribute to Franz Halberg, MD. PMID- 26870865 TI - Response. PMID- 26870866 TI - Response. PMID- 26870868 TI - Duty of candour. PMID- 26870869 TI - What does revalidation mean for you? PMID- 26870870 TI - Smoke screens. PMID- 26870871 TI - European influence. PMID- 26870872 TI - Bond Activation by Metal-Carbene Complexes in the Gas Phase. AB - "Bare" metal-carbene complexes, when generated in the gas phase and exposed to thermal reactions under (near) single-collision conditions, exhibit rather unique reactivities in addition to the well-known metathesis and cyclopropanation processes. For example, at room temperature the unligated [AuCH2](+) complex brings about efficient C-C coupling with methane to produce C2Hx (x = 4, 6), and the couple [TaCH2](+)/CO2 gives rise to the generation of the acetic acid equivalent CH2?C?O. Entirely unprecedented is the thermal extrusion of a carbon atom from halobenzenes (X = F, Cl, Br, I) by [MCH2](+) (M = La, Hf, Ta, W, Re, Os) and its coupling with the methylene ligand to deliver C2H2 and [M(X)(C5H5)](+). Among the many noteworthy C-N bond-forming processes, the formation of CH3NH2 from [RhCH2](+)/NH3, the generation of CH2?NH2(+) from [MCH2](+)/NH3 (M = Pt, Au), and the production of [PtCH?NH2](+) from [PtCH2](+)/NH3 are of particular interest. The latter species are likely to be involved as intermediates in the platinum-mediated large-scale production of HCN from CH4/NH3 (the DEGUSSA process). In this context, a few examples are presented that point to the operation of co-operative effects even at a molecular level. For instance, in the coupling of CH4 with NH3 by the heteronuclear clusters [MPt](+) (M = coinage metal), platinum is crucial for the activation of methane, while the coinage metal M controls the branching ratio between the C-N bond forming step and unwanted soot formation. For most of the gas-phase reactions described in this Account, detailed mechanistic insight has been derived from extensive computational work in conjunction with time-honored labeling and advanced mass-spectrometry-based experiments, and often a coherent description of the experimental findings has been achieved. As for some transition metals, in particular those from the third row, the metal-carbene complexes can be formed directly from methane, coupling of the so-generated [MCH2] species with an inert molecule such as CH4, CO2, or NH3 constitutes a route to activate and functionalize methane under ambient conditions. Clearly, while these gas-phase studies cannot be translated directly to formally related processes in solution or those that occur at a surface, they nevertheless provide a conceptual mechanistic understanding and permit researchers to probe directly the remarkable intrinsic features of these elusive molecules and, in a broader context, help to identify the active site of a catalyst, the so-called "aristocratic atoms". PMID- 26870873 TI - Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds with Hypervalent Iodine Reagents. AB - Alkynes have found widespread applications in synthetic chemistry, biology, and materials sciences. In recent years, methods based on electrophilic alkynylation with hypervalent iodine reagents have made acetylene synthesis more flexible and efficient, but they lead to the formation of one equivalent of an iodoarene as side-product. Herein, a more efficient strategy involving a copper-catalyzed oxy alkynylation of diazo compounds with ethynylbenziodoxol(on)e (EBX) reagents is described, which proceeds with generation of nitrogen gas as the only waste. This reaction is remarkable for its broad scope in both EBX reagents and diazo compounds. In addition, vinyl diazo compounds gave enynes selectively as single geometric isomers. The functional groups introduced during the transformation served as easy handles to access useful building blocks for synthetic and medicinal chemistry. PMID- 26870874 TI - 9-Fluorenylmethyl (Fm) Disulfides: Biomimetic Precursors for Persulfides. AB - The development of a functional disulfide, FmSSPy-A (Fm = 9-fluorenylmethyl; Py = pyridinyl), is reported. It can effectively convert small molecule and protein thiols (-SH) to form -S-SFm adducts under mild conditions. This method allows for a H2S-free and biomimetic protocol to generate highly reactive persulfides (in their anionic forms). The high nucleophilicity of persulfides toward a number of thiol-blocking reagents is also demonstrated. The method holds promise for further understanding the chemical biology of persulfides and S-sulfhydration. PMID- 26870875 TI - Quantitation of Key Tastants and Re-engineering the Taste of Parmesan Cheese. AB - Targeted quantitation of 65 candidate taste compounds and ranking on the basis of dose-over-threshold (DoT) factors, followed by taste re-engineering and omission experiments in aqueous solution as well as in a cheese-like model matrix, led to the identification of a total of 31 key tastants (amino acids, organic acids, fatty acids, biogenic amines, and minerals) with DoT factors >=1.0 and a total of 15 subthreshold, but kokumi-enhancing, gamma-glutamyl peptides in extraordinarily high concentrations of 20468 MUmol/kg. Among the gamma-glutamyl peptides, gamma Glu-Gly, gamma-Glu-Ala, gamma-Glu-Thr, gamma-Glu-Asp, gamma-Glu-Lys, gamma-Glu Glu, gamma-Glu-Trp, gamma-Glu-Gln, and gamma-Glu-His have been identified for the first time in Parmesan cheese. The excellent match of the sensory profile of the taste recombinants and the authentic cheese demonstrated the identified taste compounds to be fully sufficient to create the characteristic taste profile of the Parmesan cheese. This molecular blueprint of a Parmesan's chemosensory signature might be a useful molecular target for visualizing analytically the changes in taste profiles throughout cheese manufacturing and opens new avenues for a more scientifically directed taste improvement of cheese by tailoring manufacturing parameters ("molecular food engineering"). PMID- 26870876 TI - Molecular-Scale Study of Aspartate Adsorption on Goethite and Competition with Phosphate. AB - Knowledge of the interfacial interactions between aspartate and minerals, especially its competition with phosphate, is critical to understanding the fate and transport of amino acids in the environment. Adsorption reactions play important roles in the mobility, bioavailability, and degradation of aspartate and phosphate. Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) measurements and density functional theory (DFT) calculations were used to investigate the interfacial structures and their relative contributions in single adsorbate and competition systems. Our results suggest three dominant mechanisms for aspartate: bidentate inner-sphere coordination involving both alpha- and gamma-COO(-), outer-sphere complexation via electrostatic attraction and H bonding between aspartate NH2 and goethite surface hydroxyls. The interfacial aspartate is mainly governed by pH and is less sensitive to changes of ionic strength and aspartate concentration. The phosphate competition significantly reduces the adsorption capacity of aspartate on goethite. Whereas phosphate adsorption is less affected by the presence of aspartate, including the relative contributions of diprotonated monodentate, monoprotonated bidentate, and nonprotonated bidentate structures. The adsorption process facilitates the removal of bioavailable aspartate and phosphate from the soil solution as well as from the sediment pore water and the overlying water. PMID- 26870877 TI - Electrocatalytic Currents from Single Enzyme Molecules. AB - Single molecule enzymology provides an opportunity to examine details of enzyme mechanisms that are not distinguishable in biomolecule ensemble studies. Here we report, for the first time, detection of the current produced in an electrocatalytic reaction by a single redox enzyme molecule when it collides with an ultramicroelectrode. The catalytic process provides amplification of the current from electron-transfer events at the catalyst leading to a measurable current. This new methodology monitors turnover of a single enzyme molecule. The methodology might complement existing single molecule techniques, giving further insights into enzymatic mechanisms and filling the gap between fundamental understanding of biocatalytic processes and their potential for bioenergy production. PMID- 26870878 TI - One-Step Synthesis and Characterization of N-Doped Carbon Nanodots for Sensing in Organic Media. AB - Photoluminescent nitrogen-doped carbon nanodots (N-doped CNDs) soluble in organic media are synthesized in a one-step synthesis from a single-source precursor (an amphiphilic polymer), which exhibits a very high quantum yield (QY = 78%), excitation wavelength-dependent emission, and upconversion emission properties. The evolution of N-doped CND formation is studied via ultraviolet-visible and photoluminescence spectroscopy. Their analytical application as an effective sensor for the direct determination of nitroaromatic explosives and byproducts is shown based on their selective response via a fluorescence quenching mechanism. The proposed method is validated in soil samples by directly using the sensor in organic media without any further treatment or additional functionalization, which is an interesting aspect for practical applications. PMID- 26870879 TI - Inhalational Alzheimer's disease: an unrecognized - and treatable - epidemic. AB - Alzheimer's disease is one of the most significant healthcare problems today, with a dire need for effective treatment. Identifying subtypes of Alzheimer's disease may aid in the development of therapeutics, and recently three different subtypes have been described: type 1 (inflammatory), type 2 (non-inflammatory or atrophic), and type 3 (cortical). Here I report that type 3 Alzheimer's disease is the result of exposure to specific toxins, and is most commonly inhalational (IAD), a phenotypic manifestation of chronic inflammatory response syndrome (CIRS), due to biotoxins such as mycotoxins. The appropriate recognition of IAD as a potentially important pathogenetic condition in patients with cognitive decline offers the opportunity for successful treatment of a large number of patients whose current prognoses, in the absence of accurate diagnosis, are grave. PMID- 26870880 TI - The relationships among the levels of oxidative and antioxidative parameters, FEV1 and prolidase activity in COPD. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by poorly reversible airflow limitations associated with an abnormal inflammatory response of the lung. METHODS: We investigated whether prolidase levels in serum, total antioxidant status, total oxidative status (TOS), and the oxidative stress index (OSI) were associated with the etiopathogenesis of COPD, and whether there is a relationship between prolidase activity and oxidative parameters and carotid artery intima-media thickness (CIMT) in patients with COPD. This study included 91 patients with COPD and 15 control cases. Routine haematological and biochemical parameters were determined in all patients. All subjects were fully informed about the study and provided consent. RESULTS: The mean age of the patients with COPD was 61.3 +/- 10.5 years and that of the control group was 56.2 +/- 12.1 years. The control group had a significantly higher plasma prolidase level than that in the COPD group. TOS and OSI levels in the control group were significantly lower than those in the COPD group. However, no significant differences were found in TALs or CIMT levels between the COPD and control groups. A negative correlation was detected between prolidase activity and age; however, no significant difference in age was observed between the two groups. CONCLUSION: These results indicate that prolidase activity decreases in patients with COPD. PMID- 26870881 TI - Pentacene on Au(1 1 1), Ag(1 1 1) and Cu(1 1 1): From physisorption to chemisorption. AB - We measured the electronic and the molecular surface structure of pentacene deposited on the (1 1 1)-surfaces of coinage metals by means of ultraviolet photoelectron spectroscopy (UPS) and low-energy electron diffraction (LEED). Pentacene is almost flat-lying in monolayers on all three substrates and highly ordered on Au(1 1 1) and on Cu(1 1 1). On Ag(1 1 1), however, weak chemisorption leads to almost disordered monolayers, both, at room temperature and at 78 K. On Cu(1 1 1) pentacene is strongly chemisorbed and the lowest unoccupied molecular orbital becomes observable in UPS by a charge transfer from the substrate. On Ag(1 1 1) and Cu(1 1 1) multilayers adopt a tilted orientation and a high degree of crystallinity. On Au(1 1 1), most likely, also in multilayers the molecular short and long axes are parallel to the substrate, leading to a distinctively different electronic structure than on Ag(1 1 1) and Cu(1 1 1). Overall, it could be demonstrated that the substrate not only determines the geometric and electronic characteristics of molecular monolayer films but also plays a crucial role for multilayer film growth. PMID- 26870882 TI - Carbon-dot-decorated TiO2 nanotube arrays used for photo/voltage-induced organic pollutant degradation and the inactivation of bacteria. AB - Photoluminescent carbon dots (c-dots) have recently attracted growing interest as a new member of the carbon-nanomaterial family. Here, we report for the first time that c-dot-decorated TiO2 nanotube arrays (c-dot/TiNTs) exhibit highly enhanced abilities regarding photo/voltage-induced organic pollutant degradation and bacterial inactivation. By applying UV irradiation (365 nm) or an electrochemical potential over 3 V (versus Ag/AgCl), an organic dye and a herbicide were efficiently degraded. Moreover, the inactivation of Gram-positive S. aureus and Gram-negative E. coli bacteria was realized on a c-dot/TiNT film. The c-dots were able to absorb light efficiently resulting in multiple exciton generation and also a reduction in the recombination of the e(-)/h(+) pair produced in c-dot/TiNT film during photo/voltage-induced degradation. It was also possible to readily regenerate the surface using ultraviolet light irradiation, leaving the whole film structure undamaged and with high reproducibility and stability. PMID- 26870883 TI - Correction to "Molecular Dynamics Simulation for the Dynamics and Kinetics of Folding Peptides in the Gas Phase". PMID- 26870884 TI - A useful tool to improve the case detection rate of primary aldosteronism: the aldosterone-renin ratio (ARR)-App. AB - The aldosterone-renin ratio is the most popular test for the case detection of primary aldosteronism, which entails the most common, albeit overlooked, form of endocrine secondary hypertension. A major hindrance to the clinical use of the aldosterone-renin ratio depends on the difficulty of achieving the calculation of this ratio, given that laboratories provide plasma aldosterone in different units of measurement, and renin is measured as plasma renin activity or direct active renin. We have therefore developed an App, which can be downloaded from the ESH website and the Apple store, to assist practising physicians in performing this calculation. Our hope is that this simple tool will help in increasing the detection rate of primary aldosteronism and ultimately the long-term cure of many hypertensive patients. PMID- 26870885 TI - Core-Shell Electrospun Fibers Encapsulating Chromophores or Luminescent Proteins for Microscopically Controlled Molecular Release. AB - Core-shell fibers are emerging as interesting microstructures for the controlled release of drugs, proteins, and complex biological molecules, enabling the fine control of microreservoirs of encapsulated active agents, of the release kinetics, and of the localized delivery. Here we load luminescent molecules and enhanced green fluorescent proteins into the core of fibers realized by coaxial electrospinning. Photoluminescence spectroscopy evidences unaltered molecular emission following encapsulation and release. Moreover, the release kinetics is microscopically investigated by confocal analysis at individual-fiber scale, unveiling different characteristic time scales for diffusional translocation at the core and at the shell. These results are interpreted by a two stage desorption model for the coaxial microstructure, and they are relevant in the design and development of efficient fibrous systems for the delivery of functional biomolecules. PMID- 26870886 TI - Endoscopic Excision of Forehead and Eyebrow Benign Tumors in Children. AB - OBJECTIVE: Direct excision of dermoid cysts of the eyebrow and forehead may lead to a prominent facial scar. Endoscopic techniques have greatly reduced the morbidity of excising benign orbitofacial masses. Access, visualization, and dissection of these masses are comparable to open approaches without the use of large or conspicuous incisions. This study evaluates the efficacy of the endoscopic approach in the treatment of dermoid cysts of the eyebrow and defines the place of this approach as an alternative to open surgery. MATERIALS AND METHODS: Between July 2008 and April 2015, a total of 23 pediatric patients (13 females and 10 males) with dermoid cysts of the brow underwent excision by endoscopy. The mean age was 11.9 months (2-32 months). The lesion was located on the lateral brow in 17 cases and on the hairless forehead in 6 cases. To assess osseous involvement, sonography and magnetic resonance imaging study were performed in 22 and 1 case, respectively. Medical photos documentation was done systematically. For those children having an excision of cyst by endoscopy, the operative time, hystopathological examination, specimen size, and hospital stay were evaluated. In addition, parents of these patients were contacted to determine satisfaction with the procedure. RESULTS: All procedures were successfully performed endoscopically. The mean operative time was 41 minutes (range 17-120 minutes). There was no intraoperative complication. The mean specimen size was 12 mm. In postoperative period, 1 patient presented edema on the forehead with uneventful course. All procedures were performed on the day surgery. The hystopathological examinations were dermoid cysts in 21 cases, hemangioma in 1 case, and dermatofibroma in 1 case. The mean follow-up was 45.5 months (4-84 months). There was no residual mass or recurrence after long follow up. Cosmetic results were excellent and all families were pleased with the outcome. CONCLUSIONS: Endoscopic excision of forehead masses and dermoid cysts of the eyebrow is safe and it has proven to be an effective and minimally invasive alternative to the conventional approach. The main advantage of this procedure is the minimization of scar visibility compared with open surgery. PMID- 26870887 TI - Changes in blood product utilization in a seven-hospital system after the implementation of a patient blood management program: A 9-year follow-up. AB - OBJECTIVES: To analyze changes in red blood cell (RBC), platelet (PLT), and plasma transfusion volumes 9 years after the implementation of a multifaceted patient blood management (PBM) program across multiple hospitals. METHODS: Between fiscal years 2007 and 2015, the annual transfusion volumes for seven hospitals in a regional healthcare system were analyzed by hospital, and between 2014 and 2015, by four service lines including emergency department, intensive care unit (ICU), medical/surgical ward, and operating room at each hospital. The number of units of RBCs administered to transfused recipients on the wards and in ICUs was also enumerated. RESULTS: For these seven hospitals combined, there was a 29.9% reduction in the number of RBCs transfused between 2007 and 2015, a 24.8% reduction in plasma units, and a 25.7% reduction in PLT units. The two largest hospitals saw some of the largest reductions in RBC transfusions (40.1, 25.1%), and plasma transfusions (26.1, 33.8%), and one of those hospitals had a 49.5% reduction in PLT transfusions. Smaller-sized hospitals also had reductions in transfusion volumes, while some volumes increased at hospitals when new or expanded clinical services were introduced. The number of RBC units per transfused recipient was generally between 1.5 and 2 units on the wards and slightly higher in the ICUs. DISCUSSION: Although the overall volume of transfusions has generally decreased at each hospital site over time, the appropriateness of the administered transfusions cannot be evaluated by these data. CONCLUSION: The system-wide implementation of a PBM program has reduced transfusion volumes. PMID- 26870888 TI - Nutrition, gut microbiota and child health outcomes. AB - PURPOSE OF REVIEW: Diet is one of the main drivers of the composition and function of the gut microbiota. The scope of this review is to summarize recent studies assessing the role of gut microbiota in clinical pediatric conditions and to review studies using nutritional approaches to favorably modify the gut microbiota to improve health outcomes in children. RECENT FINDINGS: New studies underscore that breastfeeding and infant diet impact the gut microbiome and metagenome. A comprehensive study using metagenomic shotgun sequencing, suggests that the cessation of breastfeeding rather than the introduction of solid foods, drives the functional maturation of the infant gut microbiome toward an adult like state. There is further support for the view that a disturbed early gut microbiota is implicated in allergic and autoimmune diseases. New studies using prebiotics, probiotics, and synbiotics in various pediatric disorders have yielded promising results, yet the evidence for specific guidelines on their use is still low. SUMMARY: Intestinal dysbiosis is associated with several pediatric disorders but a cause-effect relationship remains to be clearly demonstrated in most conditions. Future studies using new systems biology approaches are anticipated to provide further insight into the functional capacities of the gut microbiome and its establishment in childhood. This may then lay the ground for improved treatment and prevention strategies targeting the gut microbiota. PMID- 26870889 TI - Neuromuscular junction degeneration in muscle wasting. AB - PURPOSE OF REVIEW: Denervation is a hallmark of age-related and other types of muscle wasting. This review focuses on recent insights and current viewpoints regarding the mechanisms and clinical relevance of maintaining the neuromuscular junction to counteract muscle wasting resulting from aging or neural disease/damage. RECENT FINDINGS: Activity-dependent regulation of autophagy, the agrin-muscle specific kinase-Lrp4 signaling axis, and sympathetic modulation are principal mechanisms involved in stabilizing the neuromuscular junction. These findings are derived from several animal models and were largely confirmed by human gene expression analysis as well as insights from rare neuromuscular diseases such as amyotrophic lateral sclerosis and congenital myasthenic syndromes. Based on these insights, agrin-derived fragments are currently being evaluated as biomarkers for age-related muscle wasting. Tuning of autophagy, of the agrin pathway, and of sympathetic input are being studied as clinical treatment of muscle wasting disorders. SUMMARY: Basic research has revealed that maintenance of neuromuscular junctions and a few signaling pathways are important in the context of age-dependent and other forms of muscle wasting. These findings have recently started to enter clinical practice, but further research needs to substantiate and refine our knowledge. PMID- 26870890 TI - Genetic and epigenetic background and protein expression profiles in relation to telomerase activation in medullary thyroid carcinoma. AB - Medullary thyroid carcinomas (MTCs) exhibit telomerase activation in strong association with shorter patient survival. To understand the background of telomerase activation we quantified TERT copy numbers and TERT promoter methylation in 42 MTCs and normal thyroid references. Gain of TERT was demonstrated by quantitative PCR in 5/39 sporadic MTC. Increased methylation index (MetI) for CpG methylation at the TERT promoter was found in sporadic MTCs (P < 0.0001) and in MEN 2 associated MTCs (P = 0.011) vs. normal thyroid tissues. MetI correlated positively with TERT gene expression (r = 0.432, P = 0.006) and negatively with telomere length (r = -0.343, P = 0.032). MTC cases with MetI above the median of 52% had shorter survival as compared to cases with lower MetI (P = 0.005 for overall survival and P = 0.007 for disease-related survival).Protein expression profiles obtained by mass spectrometry were then studied in relation to telomerase activation in MTCs. Comparing protein levels between tumors defined by telomerase activity status, 240 proteins were associated with telomerase activity. Among telomerase activation positive cases a set of proteins was found to discriminate between MTCs with high and low TERT gene expression with enrichment for proteins involved in telomerase regulation. XRCC5 mRNA expression was found increased in MTCs vs. normal thyroid (P = 0.007). In conclusion the findings suggest a role for TERT copy number gain, TERT promoter methylation and XRCC5 expression in telomerase activation and telomere maintenance of MTC. PMID- 26870891 TI - Molecular spectrum of TP53 mutations in plasma cell dyscrasias by next generation sequencing: an Italian cohort study and overview of the literature. AB - The prevalence of TP53 mutations greatly varies between tumor types; in multiple myeloma (MM) they were rarely detected at presentation, while increased frequency was reported with disease progression. Using next-generation sequencing, we analyzed TP53 exons 4-9 in a large representative cohort comprising patients with MM at diagnosis and more aggressive forms of plasma cell (PC) dyscrasia, identifying mutations in 4/129 (3%) MM, 6/24 (25%) primary PC leukemia, and 2/10 (20%) secondary PC leukemia cases. A similar increase in prevalence associated with disease aggressiveness (5%, 29.2% and 44%, respectively) was observed for TP53 deletion. Interestingly, in five patients mutations were not concomitant with TP53 deletion. Furthermore, longitudinal analysis revealed the acquisition of TP53 mutations in three of nineteen cases analyzed at relapse. Identified variants were mostly missense mutations concentrated in the DNA binding domain, only partly reflecting the pattern globally observed in human cancers. Our data confirm that TP53 mutations are rare in MM at presentation and rather represent a marker of progression, similarly to del(17p); however, their occurrence even in absence of deletions supports the importance of their assessment in patients with PC dyscrasia, in terms of both risk stratification and therapeutic implications. PMID- 26870892 TI - RHAMM splice variants confer radiosensitivity in human breast cancer cell lines. AB - Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify patients for adjuvant therapies. Recently, a role of the receptor of hyaluronan-mediated motility (RHAMM) has been suggested for tumor progression. Our aim was (i) to investigate the prognostic value of RHAMM in breast cancer and (ii) to unravel its potential function in the radiosusceptibility of breast cancer cells. We demonstrate that RHAMM mRNA expression in breast cancer biopsies is inversely correlated with tumor grade and overall survival. Radiosusceptibility in vitro was evaluated by sub-G1 analysis (apoptosis) and determination of the proliferation rate. The potential role of RHAMM was addressed by short interfering RNAs against RHAMM and its splice variants. High expression of RHAMMv1/v2 in p53 wild type cells (MCF-7) induced cellular apoptosis in response to ionizing radiation. In comparison, in p53 mutated cells (MDA-MB-231) RHAMMv1/v2 was expressed sparsely resulting in resistance towards irradiation induced apoptosis. Proliferation capacity was not altered by ionizing radiation in both cell lines. Importantly, pharmacological inhibition of the major ligand of RHAMM, hyaluronan, sensitized both cell lines towards radiation induced cell death. Based on the present data, we conclude that the detection of RHAMM splice variants in correlation with the p53 mutation status could help to predict the susceptibility of breast cancer cells to radiotherapy. Additionally, our studies raise the possibility that the response to radiotherapy in selected cohorts may be improved by pharmaceutical strategies against RHAMM and its ligand hyaluronan. PMID- 26870893 TI - Knockdown of Golgi phosphoprotein 2 inhibits hepatocellular carcinoma cell proliferation and motility. AB - Golgi phosphoprotein 2 (GP73) is highly expressed in hepatocellular carcinoma (HCC) cells, where it serves as a biomarker and indicator of disease progression. We used MTS assays, anchorage-independent cell colony formation assays and a xenograft tumor model to show that GP73-specific siRNAs inhibit HCC proliferation in HepG2, SMMC-7721, and Huh7 cell lines and in vivo. Following GP73 silencing, levels of p-Rb, a factor related to metastasis, were reduced, but cell cycle progression was unaffected. Our results suggest that GP73 silencing may not directly suppress proliferation, but may instead inhibit cell motility. Results from proliferation assays suggest GP73 reduces expression of epithelial mesenchymal transition (EMT)-related factors and promotes cell motility, while transwell migration and invasion assays indicated a possible role in metastasis. Immunofluorescence co-localization microscopy and immunoblotting showed that GP73 decreases expression of N-cadherin and E-cadherin, two key factors in EMT, which may in turn decrease intracellular adhesive forces and promote cell motility. This study confirmed that GP73 expression leads to increased expression of EMT related proteins and that GP73 silencing reduces HCC cell migration in vitro. These findings suggest that GP73 silencing through siRNA delivery may provide a novel low-toxicity therapy for the inhibition of tumor proliferation and metastasis. PMID- 26870896 TI - Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women. PMID- 26870895 TI - Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma. AB - BACKGROUND: Gastric cancer is one of the main causes of global mortality. Here, reactive oxygen species (ROS) could largely contribute to gastric carcinogenesis. Hence, the present work was aimed to assess the role of ROS, oxidant status, NADPH oxidases (NOXs) expression, during human gastric adenocarcinoma. METHODS: We obtained subcellular fraction from samples of gastric mucosa taken from control subjects (n = 20), and from 40 patients with gastric adenocarcinoma, as well as samples of distant areas (tumour-free gastric mucosa). RESULTS: Parameters indicative of lipid peroxidation and cell proliferation were selectively increased in both tumour-free and in cancerous gastric mucosa, despite of glutathione (GSH) content, glutathione reductase (GR) and superoxide dismutase (SOD) activities were increased in the adenocarcinoma. These high levels of antioxidant defences inversely correlated with down-regulated expression for NOX2 and 4; however, over-expression of NOX1 occurred with increased caspase-3 activity and overexpressed checkpoint 1 (MDC1) and cyclin D1 proteins. In the tumour-free mucosa an oxidant stress took place, without changing total GSH but with decreased activities for GR and mitochondrial SOD; moreover, over-expression of checkpoint 1 (MDC1) correlated with lower NOX2 and 4 expression in this mucosa. CONCLUSIONS: Chronically injured gastric mucosa increases lipoperoxidative events and cell proliferation. In the adenocarcinoma, cell proliferation was further enhanced, oxidant stress decreased which seemed to be linked to NOX1, MDC1 and cyclin D1 over-expression, but with a lower NOXs activity leading a 'low tone' of ROS formation. Therefore, our results could be useful for early detection and treatment of gastric adenocarcinoma. PMID- 26870894 TI - First in-depth analysis of the novel Th2-type cytokines in salmonid fish reveals distinct patterns of expression and modulation but overlapping bioactivities. AB - IL-4 and IL-13 are closely related canonical type-2 cytokines in mammals and have overlapping bioactivities via shared receptors. They are frequently activated together as part of the same immune response and are the signature cytokines produced by T-helper (Th)2 cells and type-2 innate lymphoid cells (ILC2), mediating immunity against extracellular pathogens. Little is known about the origin of type-2 responses, and whether they were an essential component of the early adaptive immune system that gave a fitness advantage by limiting collateral damage caused by metazoan parasites. Two evolutionary related type-2 cytokines, IL-4/13A and IL-4/13B, have been identified recently in several teleost fish that likely arose by duplication of an ancestral IL-4/13 gene as a consequence of a whole genome duplication event that occurred at the base of this lineage. However, studies of their comparative expression levels are largely missing and bioactivity analysis has been limited to IL-4/13A in zebrafish. Through interrogation of the recently released salmonid genomes, species in which an additional whole genome duplication event has occurred, four genomic IL-4/13 loci have been identified leading to the cloning of three active genes, IL-4/13A, IL 4/13B1 and IL-4/13B2, in both rainbow trout and Atlantic salmon. Comparative expression analysis by real-time PCR in rainbow trout revealed that the IL-4/13A expression is broad and high constitutively but less responsive to pathogen associated molecular patterns (PAMPs) and pathogen challenge. In contrast, the expression of IL-4/13B1 and IL-4/13B2 is low constitutively but is highly induced by viral haemorrhagic septicaemia virus (VHSH) infection and during proliferative kidney disease (PKD) in vivo, and by formalin-killed bacteria, PAMPs, the T cell mitogen PHA, and the T-cell cytokines IL-2 and IL-21 in vitro. Moreover, bioactive recombinant cytokines of both IL-4/13A and B were produced and found to have shared but also distinct bioactivities. Both cytokines rapidly induce the gene expression of antimicrobial peptides and acute phase proteins, providing an effector mechanism of fish type-2 cytokines in immunity. They are anti inflammatory via up-regulation of IL-10 and down-regulation of IL-1beta and IFN gamma. They modulate the expression of cellular markers of T cells, macrophages and B cells, the receptors of IFN-gamma, the IL-6 cytokine family and their own potential receptors, suggesting multiple target cells and important roles of fish type-2 cytokines in the piscine cytokine network. Furthermore both cytokines increased the number of IgM secreting B cells but had no effects on the proliferation of IgM+ B cells in vitro. Taken as a whole, fish IL-4/13A may provide a basal level of type-2 immunity whilst IL-4/13B, when activated, provides an enhanced type-2 immunity, which may have an important role in specific cell-mediated immunity. To our knowledge this is the first in-depth analysis of the expression, modulation and bioactivities of type-2 cytokines in the same fish species, and in any early vertebrate. It contributes to a broader understanding of the evolution of type-2 immunity in vertebrates, and establishes a framework for further studies and manipulation of type-2 cytokines in fish. PMID- 26870897 TI - Long-term follow-up of endoscopic third ventriculostomy performed in the pediatric population. AB - OBJECTIVE Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus and avoids the risk for foreign-body infection associated with ventriculoperitoneal (VP) shunts. The short-term failure rate of ETV strongly depends on the indications for its use but is generally thought to be lower in the long term than that of VP shunts. However, few studies are available with long-term follow-up data of ETV for hydrocephalus in children. The authors reviewed the long-term success of ETV at their institution to investigate the rate of any late failures of this procedure. METHODS Between April 1998 and June 2006, 113 children (including neonates and children up to 16 years old) had primary or secondary ETV for different causes of hydrocephalus. The patients' medical records and the authors' electronic operation database were reviewed for evidence of additional surgery (i.e., repeat ETV or VP shunt insertion). These records were checked at both the pediatric and adult neurosurgical hospitals for those patients who had their care transferred to adult services. RESULTS The median length of follow-up was 8.25 years (range 1 month to 16 years). Long-term follow-up data for 96 patients were available, 47 (49%) of whom had additional ETV or VP shunt insertion for ETV failure. Twenty patients (21%) had a second procedure within 1 month, 17 patients (18%) between 1 and 12 months, 7 patients (7%) between 1 and 5 years, and 3 patients (3%) between 5 and 8 years. CONCLUSIONS In the authors' series, ETV had an initial early failure rate for the treatment of pediatric hydrocephalus as reported previously, and this rate significantly depended on patient age and hydrocephalus etiology. Once stabilized and effective, ETV appeared to be durable but not guaranteed, and some late decline in effectiveness was observed, with some ETV failures occurring many years later. Thus, successful ETV in children cannot be guaranteed for life, and some form of follow-up is recommended long term into adulthood. PMID- 26870899 TI - Tailored disconnection based on presurgical evidence in catastrophic epilepsy: report of 2 cases. AB - Catastrophic epilepsy in infants, often due to extensive cortical dysplasia, has devastating consequences with respect to brain development. Conventional lobar, multilobar, or hemispheric resection in these infants is challenging, carrying an increased operative risk compared with that in older children. Removing a larger tissue volume versus removing or disconnecting the epileptogenic region does not always guarantee better seizure outcome. The authors describe 2 infants with catastrophic epilepsy who benefited from individually tailored disconnections based on a hypothesized epileptogenic zone following intensive presurgical evaluation. Two infants with catastrophic epilepsy and epileptic spasms underwent leukotomies between 3 and 12 months of age. They were followed up postoperatively for 19-36 months. Both patients had 90%-100% seizure reduction and a significantly improved neurodevelopmental outcome without postoperative complication. Cortical malformation was seen in both patients. Modifications of established surgical disconnection techniques, tailored to each patient's specific epileptogenic zone, optimized seizure and neurodevelopmental outcomes while minimizing the risks associated with more extensive resections. PMID- 26870898 TI - Mesial temporal lobe morphology in intractable pediatric epilepsy: so-called hippocampal malrotation, associated findings, and relevance to presurgical assessment. AB - OBJECTIVE Diagnostic criteria for hippocampal malrotation (HIMAL) on brain MRI typically include a rounded hippocampus, vertical collateral sulcus, and architectural blurring. Relationship to epileptogenesis remains speculative, and usefulness for surgical guidance is unknown. The study was performed to determine the prevalence of hippocampal rotational anomalies in a cohort of pediatric patients with intractable epilepsy undergoing evaluation for surgery and to determine the significance of this finding in the context of surgical planning. METHODS Forty-eight surgically treated children with intractable epilepsy were compared with matched healthy subjects; reviewers were blinded to surgical side. Each temporal lobe was evaluated for rounded hippocampus, blurring, vertical collateral sulcus, wide choroidal fissure, enlarged temporal horn, low fornix, hippocampal signal, and findings of hippocampal sclerosis. A mesial temporal lobe (MTL) score was calculated by summing the number of features, and the collateral sulcus angle (CSA) was measured in each temporal lobe. Surgical side, pathological diagnosis, and imaging findings elsewhere in the brain were tabulated. Presence of HIMAL, associated imaging features, and MTL score were compared between sides, between epilepsy and control groups, in relationship to side of surgery, and in relationship to postoperative outcome. RESULTS Only 3 epilepsy patients (6.2%) and no controls exhibited all 3 features of HIMAL (p = 0.12). Eight of 48 (16.7%) epilepsy versus 2 of 48 (4.6%) control subjects had both a rounded hippocampus and vertical collateral sulcus (suggesting HIMAL) (p = 0.045). In control and epilepsy subjects, most findings were more prevalent on the left, and the left CSA was more vertical (p < 0.0001). Epilepsy subjects had higher MTL scores (z = -2.95, p = 0.002) and more acute CSAs (p = 0.04) than controls. Only lateralizing raw MTL score had a significant association with surgical side (p = 0.03, OR 7.33); however, this was not significant when hippocampal sclerosis cases were excluded. HIMAL findings were more prevalent and MTL scores were higher in patients with resections involving the temporal lobes. On group analysis, HIMAL findings did not predict eventual surgical side and did not predict outcome, although the numbers are small. In 4 patients the abnormally rotated hippocampus was resected and showed hippocampal sclerosis and/or dysplastic changes on histopathology. All of these patients had a good outcome after surgery. CONCLUSIONS While increased in prevalence in children with intractable epilepsy, imaging findings of HIMAL did not have preoperative lateralizing utility in this group. Findings of HIMAL (including round hippocampus, architectural blurring, and vertical collateral sulcus) did not predict outcome after surgery, although the small number of patients with these findings limits evaluation. In the small number of patients in which the malrotated hippocampus was removed, outcome was good. Further research is needed to continue to define this association in children with intractable epilepsy, focusing on a temporal lobe cohort. PMID- 26870900 TI - Sweet Dream Liquid Chinese Medicine Ameliorates Learning and Memory Deficit in a Rat Model of Paradoxical Sleep Deprivation through the ERK/CREB Signaling Pathway. AB - Sweet dream oral liquid (SDOL), a traditional Chinese herbal compound contains 17 traditional Chinese medicines. It has various pharmacological effects, such as improving brain dysfunction and increasing sleeping quality. This study investigated the neuroprotective effect and the underlying mechanisms of SDOL impaired hippocampus learning and memory-induced paradoxical sleep deprivation (PSD) in rats. Sixty Male Wistar rats were randomly divided into six groups. Before PSD, SDOL treatment group rats were intragastrically administered SDOL for 25 days at dose of 2.1, 4.2, and 8.4 mL/kg body weight per day. Normal control group, large platform control group, and PSD groups were treated with normal saline instead of SDOL. After 25 days treatment, PSD and SDOL groups were deprived of paradoxical sleep for 72 h. Then two behavioral studies were conducted to test the spatial learning and memory ability using the open field test and Morris water maze test. Expression of the c-fos, c-jun, cyclic AMP response element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), mitogen-activated protein kinases (MAPK)/ERK kinase (MEK), and p CREB, p-ERK, and p-MEK in the hippocampus were also assayed by western blot. In this study, PSD decreased the levels of p-CREB, p-ERK, p-MEK, c-fos, and c-jun. However, SDOL treatment increased expressions of these proteins. Our results showed that SDOL improved 72-h PSD-induced cognitive impairment. These affects may be mediated by increasing the contents of c-fos, c-jun, and p-CREB/ERK signaling. PMID- 26870901 TI - Role of reactive oxygen species in age-related neuromuscular deficits. AB - Although it is now clear that reactive oxygen species (ROS) are not the key determinants of longevity, a number of studies have highlighted the key role that these species play in age-related diseases and more generally in determining individual health span. Age-related loss of skeletal muscle mass and function is a key contributor to physical frailty in older individuals and our current understanding of the key areas in which ROS contribute to age-related deficits in muscle is through defective redox signalling and key roles in maintenance of neuromuscular integrity. This topical review will describe how ROS stimulate adaptations to contractile activity in muscle that include up-regulation of short term stress responses, an increase in mitochondrial biogenesis and an increase in some catabolic processes. These adaptations occur through stimulation of redox regulated processes that lead to the activation of transcription factors such as NF-kappaB, AP-1 and HSF1 which mediate changes in gene expression. They are attenuated during ageing and this appears to occur through an age-related increase in mitochondrial hydrogen peroxide production. The potential for redox mediated cross-talk between motor neurons and muscle is also described to illustrate how ROS released from muscle fibres during exercise may help maintain the integrity of axons and how the degenerative changes in neuromuscular structure that occur with ageing may contribute to mitochondrial ROS generation in skeletal muscle fibres. PMID- 26870902 TI - Critical Situations in Daily Life as Experienced by Patients With Inflammatory Bowel Disease. AB - Crohn disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are chronic and have a fluctuating clinical course that impacts daily life. Daily life with a chronic disease involves thinking and worrying about the limitations that chronic disease causes. Knowledge about how patients who suffer from IBD manage critical incidents in daily life is lacking. The aim of the study was to describe how patients living with IBD experience critical incidents in daily life in relation to their disease and symptoms. Thirty adult patients were interviewed focusing on critical incidents in daily life. Data were analyzed using the critical incident technique. The study comprised 224 critical incidents and was grouped into 21 subcategories and 5 categories: losing bowel control, having a body that smells, being unable to meet own and others' expectations, not being believed or seen, and experiencing frustration due to side effects and ineffective treatment. These categories formed one main area describing the overall result "The bowels rule life." The uncertain nature of IBD created critical incidents in which the bowel ruled life, causing patients to avoid social interaction. It also placed considerable demands on the family and sometimes had a negative effect on the afflicted person's career. PMID- 26870903 TI - Actinophage R4 integrase-based site-specific chromosomal integration of non replicative closed circular DNA. AB - The actinophage R4 integrase (Sre)-based molecular genetic engineering system was developed for the chromosomal integration of multiple genes in Escherichia coli. A cloned DNA fragment containing two attP sites, green fluorescent protein (gfp) as a first transgene, and an antibiotic resistance gene as a selection marker was self-ligated to generate non-replicative closed circular DNA (nrccDNA) for integration. nrccDNA was introduced into attB-inserted E. coli cells harboring the plasmid expressing Sre by electroporation. The expressed Sre catalyzed site specific integration between one of the two attP sites on nrccDNA and the attB site on the E. coli chromosome. The integration frequency was affected by the chromosomal location of the target site. A second nrccDNA containing two attB sites, lacZalpha encoding the alpha fragment of beta-galactosidase as a transgene, and another antibiotic resistance gene was integrated into the residual attP site on the gfp-integrated E. coli chromosome via one of the two attB sites according to reiterating site-specific recombination. The integrants clearly exhibited beta-galactosidase activity and green fluorescence, suggesting the simultaneous expression of multiple recombinant proteins in E. coli. The results of the present study showed that a step-by-step integration procedure using nrccDNA achieved the chromosomal integration of multiple genes. PMID- 26870904 TI - Generalized pustular psoriasis associated with Turner syndrome and dilated cardiomyopathy. PMID- 26870905 TI - Relationship between motivational style and glycemic control in Jordanian patients with type 2 diabetes mellitus. AB - BACKGROUND: Although, there is increased recognition of the importance of blood glucose control and diabetes education in type 2 diabetes mellitus (T2DM), the relationship between motivation and long term outcomes, glycemic control, are lacking. The primary aims of the present study were to: (i) describe the motivational style of Jordanian patients with T2DM regarding self-care management, taking medications, and self-monitoring of blood glucose (SMBG), as well as following therapeutic dietary instructions and exercising regularly; and b) examine the significance of these factors in predicting glycemic control. METHODS: A package including a treatment self-regulation questionnaire concerning diabetes, was administered to a convenience sample of 110 patients with T2DM. In addition, the most recent HbA1c results were extracted from the patients' medical records. RESULTS: Fifty-eight patients (52.7 %) reported being intrinsically motivated with regard to taking medication and regular SMBG, whereas half the participants (50 %) were intrinsically motivated to follow therapeutic dietary instructions and regular exercise. Patients who were intrinsically motivated were 8.3-fold more likely (95 % confidence interval [CI] 1.44-47.86) to have glycemic control than those reporting extrinsic motivation. In addition, those who were intrinsically motivated to follow therapeutic dietary instructions and exercise regularly were 10.50-fold more likely (95 % CI 2.50-48.78) times more likely to report glycemic control than those reporting extrinsic motivation. CONCLUSION: Interventional strategies should focus on promoting intrinsic motivation in order to enhance glycemic control. PMID- 26870907 TI - Aripiprazole Use in Children Diagnosed with Down Syndrome and Comorbid Autism Spectrum Disorders. PMID- 26870906 TI - Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature. AB - Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaine-seeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals. PMID- 26870908 TI - Surface etching, chemical modification and characterization of silicon nitride and silicon oxide--selective functionalization of Si3N4 and SiO2. AB - The ability to selectively chemically functionalize silicon nitride (Si3N4) or silicon dioxide (SiO2) surfaces after cleaning would open interesting technological applications. In order to achieve this goal, the chemical composition of surfaces needs to be carefully characterized so that target chemical reactions can proceed on only one surface at a time. While wet chemically cleaned silicon dioxide surfaces have been shown to be terminated with surficial Si-OH sites, chemical composition of the HF-etched silicon nitride surfaces is more controversial. In this work, we removed the native oxide under various aqueous HF-etching conditions and studied the chemical nature of the resulting Si3N4 surfaces using infrared absorption spectroscopy (IRAS), x-ray photoelectron spectroscopy (XPS), low energy ion scattering (LEIS), and contact angle measurements. We find that HF-etched silicon nitride surfaces are terminated by surficial Si-F and Si-OH bonds, with slightly subsurface Si-OH, Si O-Si, and Si-NH2 groups. The concentration of surficial Si-F sites is not dependent on HF concentration, but the distribution of oxygen and Si-NH2 displays a weak dependence. The Si-OH groups of the etched nitride surface are shown to react in a similar manner to the Si-OH sites on SiO2, and therefore no selectivity was found. Chemical selectivity was, however, demonstrated by first reacting the -NH2 groups on the etched nitride surface with aldehyde molecules, which do not react with the Si-OH sites on a SiO2 surface, and then using trichloro-organosilanes for selective reaction only on the SiO2 surface (no reactivity on the aldehyde-terminated Si3N4 surface). PMID- 26870910 TI - Mid- and long-term anxiety levels associated with presymptomatic testing of Huntington's disease, Machado-Joseph disease, and familial amyloid polyneuropathy. AB - OBJECTIVE: To study anxiety as a variable of the mid- and long-term psychological impact of pre-symptomatic testing for three autosomal dominant late-onset disorders - Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloid polyneuropathy (FAP) TTR V30M - in a Portuguese sample. METHODS: This cross-sectional study included 203 participants: 170 (83.7%) underwent pre symptomatic testing for FAP, 29 (14.3%) for HD, and 4 (2%) for MJD. Of the 203 participants, 73 (36.0%) were asymptomatic carriers, 29 (14.5%) were symptomatic carriers, 9 (4.5%) were diagnosed with FAP and had a liver transplant, and 89 (44.5%) were non-carriers. Most were women (58.1%) and married (66.5%). The anxiety variable was assessed using the Zung Self-Rating Anxiety Scale (SAS). RESULTS: The anxiety scores were higher for symptomatic carriers and for those who underwent psychological support consultations over the years. For symptomatic carriers, the mean scores were superior to 40 points, which reflects clinical anxiety. CONCLUSION: Although it was not possible to differentiate between the mid- and long-term psychological impacts, this study supports the conclusion that the proximity to the age of symptoms onset might be a trigger for anxiety. PMID- 26870909 TI - Cognition and functioning in bipolar depression. AB - OBJECTIVES: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. METHODS: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. RESULTS: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). CONCLUSION: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes. PMID- 26870911 TI - Eating behaviors, body image, perfectionism, and self-esteem in a sample of Portuguese girls. AB - OBJECTIVE: Eating disorders are an increasingly prevalent health problem among adolescent girls. It is well known that biological, psychosocial, and family related factors interact in the development of this group of disorders. However, the mechanisms underlying the interaction between these variables are still poorly understood, especially in Portuguese adolescents. The aim of this study was to investigate the relationship between eating behaviors, body dissatisfaction, self-esteem, and perfectionism in a sample of Portuguese girls. METHOD: A community sample of 575 Portuguese girls attending secondary school, answered self-report questionnaires including data on weight, height, and the Portuguese versions of the Contour Figures Rating Scale, the Child and Adolescent Perfectionism Scale, the Children Eating Attitudes Test, and the Rosenberg Self Esteem Scale. SPSS version 20.0 for Windows was used for statistical analyses. RESULTS: High scores in the Children Eating Attitudes Test were associated with significantly higher levels of body dissatisfaction (r = 0.339), socially prescribed perfectionism (r = 0.175), self-oriented perfectionism (r = 0.211), and low self-esteem (r = -0.292) (all p < 0.001). Self-oriented perfectionism partially mediated the relation between body dissatisfaction and disordered eating behaviors. CONCLUSION: In this sample, dysfunctional eating behaviors appeared to correlate strongly with body dissatisfaction, low self-esteem, and perfectionism in girls. These themes should be addressed among female adolescents in the community. PMID- 26870912 TI - Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder. AB - OBJECTIVE: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. METHODS: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. RESULTS: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. CONCLUSION: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease. PMID- 26870913 TI - Depression, quality of life, and body composition in patients with end-stage renal disease: a cohort study. AB - Objective:: To prospectively evaluate depressive symptoms, nutritional status, and quality of life (QoL) and search for possible associations in patients with end-stage renal disease undergoing hemodialysis. Methods:: A cohort study of 104 adult patients with end-stage renal disease undergoing hemodialysis was conducted. Anthropometric, clinical, and biochemical variables were evaluated after a midweek hemodialysis session. The participants' body composition was assessed by direct segmental multi-frequency bioimpedance analysis. The WHOQOL Bref questionnaire was used to evaluate QoL. Participants were separated into two groups - depressive symptoms and no depressive symptoms - at inclusion and evaluated annually for 2 years thereafter using the Beck Depression Inventory. Survival analysis used the Kaplan-Meier method and Cox regression analysis for the goodness of fit of associated factors. All-cause mortality was the outcome of interest. Results:: Participants' mean age was 55.3+/-15.6 years, 60% were male, and the median time on hemodialysis was 17.5 (8.0-36.8) months. Thirty-two patients had depressive symptoms and a significantly lower QoL compared with the 72 patients in the no depressive symptoms group. The fitted outcome model showed that lean body mass had a protective effect against all-cause mortality (hazard ratio [HR] = 0.89; 95%CI 0.80-0.99; p = 0.038). Conclusion:: Depressive symptoms were highly prevalent in the cohort, and correlated with the physical and psychological components of the QoL life questionnaire, as well as with C reactive protein and phosphorus levels. Lean body mass was protective for the assessed outcome. PMID- 26870914 TI - Long-term outcome of insulin pump therapy: reduction of hypoglycaemia and impact on glycaemic control. AB - AIMS: To determine the long-term outcome of continuous subcutaneous insulin infusion (CSII) in Type 1 diabetes according to Catalan National Health Service indications. METHODS: Retrospective observational study including 178 patients with Type 1 diabetes who started CSII treatment in our centre (2003-2008). All patients were followed in our CSII programme for outpatients for at least 5 years. Data on annual HbA1c levels were collected, and the main indication for starting CSII was analysed. RESULTS: Twenty-seven of 178 patients were excluded because of loss to follow-up or withdrawal from CSII, thus 151 patients (aged 37.4 +/- 10.5 years, 64% women) were analysed. The main indications for starting CSII were suboptimal metabolic control (60.9%), severe hypoglycaemia/hypoglycaemia unawareness (25.5%) and others (13.6%). HbA1c was 64 +/- 13 mmol/mol (8.0 +/- 1.2%) at the start of CSII and 62 +/- 13 mmol/mol (7.8 +/- 1.2%) after 5 years in the total cohort (P = 0.1). The severe hypoglycaemia rates were 0.66 +/- 1.61 and 0.17 +/- 0.42 episodes/patient/year (P < 0.001). In patients with suboptimal metabolic control, HbA1c decreased from 68 +/- 12 mmol/mol (8.4 +/- 1.1%) to 64 +/- 14 mmol/mol (8.0 +/- 1.3%) (P = 0.016), with 37.4% of those in this group having an HbA1c <= 58 mmol/mol (7.5%) after 5 years. In patients starting CSII due to severe hypoglycaemia the problem was considered resolved in 93%, and in 64% of those starting CSII because of suboptimal glycaemic control, HbA1c improved significantly. CONCLUSIONS: CSII therapy achieves and maintains its efficacy mainly in terms of reducing severe hypoglycaemia. In the whole group of patients, the reduction in HbA1c is transient and disappears after 5 years. PMID- 26870916 TI - Avoiding the first cesarean section--results of structured organizational and cultural changes. AB - INTRODUCTION: In 2006 the overall rates of instrumental deliveries (10%) and cesarean sections (CS) (20%) were high in our unit. We decided to improve quality of care by offering more women a safe and attractive normal vaginal delivery. The target group was primarily nulliparous women at term with spontaneous onset of labor and cephalic presentation. MATERIAL AND METHODS: Implementation of a "nine item list" of structured organizational and cultural change in Linkoping 2006-15. The nine items include monitoring of obstetric results, recruitment of a midwife coordinator, risk classification of women, introduction of three different midwife competence levels, improved teamwork, obstetrical morning round, fetal monitoring skills, obstetrical skills training, and public promotion of the strategy. RESULTS: The CS rate in nulliparous women at term with spontaneous onset of labor decreased from 10% in 2006 to 3% in 2015. During the same period the overall CS rate dropped from 20% to 11%. The prevalence of children born at the unit with umbilical cord pH <7 and Apgar score <4 at 5 min were the same over the years studied. At present, 95.2% of women delivering at our unit are satisfied with their delivery experience. CONCLUSIONS: The CS rates have declined after implementing the nine items of organizational and cultural changes. It seems that a specific and persistent multidisciplinary activity with a focus on the Robson group 1 can reduce CS rates without increased risk of neonatal complications. PMID- 26870917 TI - The ethics of complexity. Genetics and autism, a literature review. AB - It is commonly believed that the etiology of autism is at least partly explained through genetics. Given the complexity of autism and the variability of the autistic phenotype, genetic research and counseling in this field are also complex and associated with specific ethical questions. Although the ethics of autism genetics, especially with regard to reproductive choices, has been widely discussed on the public fora, an in depth philosophical or bioethical reflection on all aspects of the theme seems to be missing. With this literature review we wanted to map the basic questions and answers that exist in the bioethical literature on autism genetics, research, counseling and reproduction, and provide suggestions as to how the discussion can proceed. We found 19 papers that fitted the description of "bioethics literature focusing on autism genetics," and analyzed their content to distill arguments and themes. We concluded that because of the complexity of autism, and the uncertainty with regard to its status, more ethical reflection is needed before definite conclusions and recommendations can be drawn. Moreover, there is a dearth of bioethical empirical studies querying the opinions of all parties, including people with autism themselves. Such empirical bioethical studies should be urgently done before bioethical conclusions regarding the aims and desirability of research into autism genes can be done. Also, fundamental philosophical reflection on concepts of disease should accompany research into the etiology of autism. PMID- 26870918 TI - Sarcocystid organisms found in bile from a dog with acute hepatitis: a case report and review of intestinal and hepatobiliary Sarcocystidae infections in dogs and cats. AB - Sarcocystidae is a family of coccidian protozoa from the phylum Apicomplexa that includes Toxoplasma, Neospora, Sarcocystis, Hammondia, and Besnoitia spp. All species undergo a 2-host sexual and asexual cycle. In the definitive host, replication is enteroepithelial, and infection is typically asymptomatic or less commonly causes mild diarrhea. Clinical disease is most frequently observed in the intermediate host, often as an aberrant infection, and is mostly associated with neurologic, muscular, or hepatic inflammation. Here, we review the literature regarding intestinal Sarcocystidae infections in dogs and cats, with emphasis on the life cycle stages and the available diagnostic assays and their limitations. We also report the diagnostic findings for an 11-year-old dog with acute neutrophilic hepatitis, biliary protozoa, and negative biliary culture. Although Toxoplasma and Neospora IgG titers were both high, PCR for these 2 organisms was negative for bile. The organisms were identified by 18S rDNA PCR as most consistent with Hammondia, either H heydorni or H triffittae. This is the first report of presumed Hammondia organisms being found in canine bile. PMID- 26870920 TI - Palladium-catalyzed direct arylation of indoles with arylsulfonyl hydrazides. AB - A novel method to synthesise 2-arylindoles is demonstrated via direct arylation of indoles with arylsulfonyl hydrazides. Under the optimized reaction conditions, the reaction well tolerates a wide variety of functional groups to afford structurally diverse 2-arylindoles in good to excellent yields at 70 degrees C. PMID- 26870919 TI - The role of diet in children's exposure to organophosphate pesticides. AB - BACKGROUND: Studies suggest that some of the greatest exposure to OPs in children occurs in agricultural communities and various pathways of exposure including the take-home pathway, proximity to orchards, and diet have been explored. However, the importance of the dietary pathway of exposure for children in agricultural communities is not well understood. OBJECTIVES: Our goal was to ascertain whether there were associations between measures of OP exposure and apple juice, fruit, and vegetable consumption across growing seasons by children of farmworkers and non-farmworkers in a rural agricultural setting. METHODS: Study participants were children of farmworker (N=100) or non-farmworker (N=100) households from a longitudinal cohort study. Dietary intake of fruits and vegetables was assessed using a "5-A-Day" abbreviated food frequency questionnaire, and exposure to OPs was characterized using three urinary di-methyl and three di-ethyl metabolite measurements per child for each of three growing seasons. We used generalized estimating equations to examine data. RESULTS: Consumption frequency of fruits and vegetables was similar between children of farmworkers and non-farmworkers and across seasons. There were a few significant trends between dimethyl metabolites (DMAP) and fruit, vegetable or apple juice consumption; however, no clear pattern held across seasons or occupation. One difference was found in vegetable consumption during the harvest season, where the farmworker families showed a significant relationship between vegetable consumption and dimethyl metabolite levels (p=0.002). We also found a significant difference in this relationship between farmworkers and non-farmworkers (p=0.001). No significant trends between fruit and vegetable consumption and diethyl (DEAP) metabolites were found. CONCLUSIONS: Our study shows the importance of considering season and parents' occupation in understanding OP exposure routes among children in an agricultural community. The impact of these factors on dietary OP exposure requires a more thorough analysis of the availability and consumption of produce from different sources including farms using pesticides where parents worked. PMID- 26870922 TI - Axial zero-field splitting in mononuclear Co(ii) 2-N substituted N-confused porphyrin: Co(2-NC3H5-21-Y-CH2C6H4CH3-NCTPP)Cl (Y = o, m, p) and Co(2-NC3H5-21 CH2C6H5-NCTPP)Cl. AB - The inner C-benzyl- and C-o-xylyl (or m-xylyl, p-xylyl)-substituted cobalt(ii) complexes of a 2-N-substituted N-confused porphyrin were synthesized from the reaction of 2-NC3H5NCTPPH (1) and CoCl2.6H2O in toluene (or o-xylene, m-xylene, p xylene). The crystal structures of diamagnetic chloro(2-aza-2-allyl-5,10,15,20 tetraphenyl-21-hydrogen-21-carbaporphyrinato-N,N',N'')zinc(ii) [Zn(2-NC3H5-21-H NCTPP)Cl; 3 ] and paramagnetic chloro(2-aza-2-allyl-5,10,15,20-tetraphenyl-21 benzyl-21-carbaporphyrinato-N,N',N'')cobalt(ii) [Co(2-NC3H5-21-CH2C6H5NCTPP)Cl; 7], and chloro(2-aza-2-allyl-5,10,15,20-tetraphenyl-21-Y-xylyl-21 carbaporphyrinato-N,N',N'')cobalt(ii) [Co(2-NC3H5-21-Y-CH2C6H4CH3NCTPP)Cl] [Y = o (8), m (9), p (10)] were determined. The coordination sphere around the Zn(2+) (or Co(2+)) ion in 3 (or 7-10) is a distorted tetrahedron (DT). The free energy of activation at the coalescence temperature Tc for the exchange of phenyl ortho protons o-H (26) with o-H (22) in 3 in a CDCl3 solvent is found to be DeltaG = 61.4 kJ mol(-1) through (1)H NMR temperature-dependent measurements. The axial zero-field splitting parameter |D| was found to vary from 35.6 cm(-1) in 7 (or 30.7 cm(-1) in 8) to 42.0 cm(-1) in 9 and 46.9 cm(-1) in 10 through paramagnetic susceptibility measurements. The magnitude of |D| can be related to the coordination sphere at the cobalt sites. PMID- 26870921 TI - Conformational Fixation of a Rectangular Antiaromatic [28]Hexaphyrin Using Rationally Installed Peripheral Straps. AB - A rectangular [28]hexaphyrin bearing outer straps at the long side has been synthesized by SN Ar reaction of [26]hexaphyrin with allyl alcohol, intramolecular olefin metathesis by using Hoveyda-Grubbs second-generation catalyst, and reduction with NaBH4 . The peripheral straps enforce a rectangular conformation for the [28]hexaphyrin, which shows Huckel antiaromatic character, as confirmed by its planar X-ray structure, a strong paratropic ring current, characteristic UV/Vis/NIR absorption features, small electrochemical HOMO-LUMO gap, and very fast S1 decay. PMID- 26870923 TI - Current Resources for Evidence-Based Practice, March/April 2016. PMID- 26870924 TI - Recent advances in understanding the enzymatic reactions of [4+2] cycloaddition and spiroketalization. AB - Diels-Alder-like [4+2] cycloaddition and ketalization of dihydroxy ketones are cyclization reactions with different mechanisms that produce characteristic cyclohexene and spiroketal units, respectively. Here, we review newly identified, naturally occurring '[4+2] cycloadditionases' and 'spiroketalases' and reveal several similarities between the two types of enzymes. During catalysis, these enzymes control product stereochemistry or/and enhance the transformation rate. They exhibit convergent evolution of [4+2] cycloaddition or spiroketalization activity, which is likely dependent on interactions of variable protein folds with specialized chemical structures. An understanding of these similarities is expected to allow for establishment of the underlying principles for the application and catalyst design of associated enzymatic reactions in organic chemistry and synthetic biology. PMID- 26870925 TI - Intraperitoneal bupivacaine with or without incisional bupivacaine for postoperative analgesia in dogs undergoing ovariohysterectomy. AB - OBJECTIVE: Intraperitoneal (IP) bupivacaine provides postoperative analgesia in dogs undergoing ovariohysterectomy (OHE) alone or in combination with incisional (INC) bupivacaine. This study investigated whether the combination of INC and IP bupivacaine is superior to IP bupivacaine alone. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Thirty-nine privately owned dogs undergoing OHE, aged 25 +/- 23 months and weighing 11.8 +/- 5.7 kg. METHODS: Dogs were premedicated with acepromazine (0.05 mg kg(-1) ) and morphine (0.5 mg kg(-1) ) intramuscularly (IM); anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Carprofen (4 mg kg(-1) ) was administered subcutaneously (SC) after intubation. Bupivacaine (3 mg kg(-1) ) IP was administered before complete closure of the linea alba to all dogs. Dogs were randomly assigned into two groups: group B received bupivacaine (n = 20; 1 mg kg(-1) ) and group S received saline (n = 19; 0.2 mL kg(-1) ) INC as a subcutaneous 'splash' before skin closure. Postoperative analgesia was assessed with a dynamic interactive visual analogue scale, the short form of the Glasgow Composite Pain Scale, and mechanical nociceptive threshold (MNT) measurement at 0.5, 1, 2, 4, 6, 8, 12 and 20 hours after surgery by one blinded observer. Parametric data were tested using t-test; nonparametric data were analysed using the two-sample Wilcoxon test (p < 0.05). RESULTS: There was no significant difference between groups with regard to age, weight, surgical and anaesthetic duration, incision length, sedation and pain scores. MNT values decreased in both groups at all time points as compared with the baseline. No dog required rescue analgesia. No postoperative complications were observed. CONCLUSION AND CLINICAL RELEVANCE: Bupivacaine IP and carprofen SC after morphine IM did provide satisfactory postoperative analgesia in dogs undergoing OHE with the anaesthetic protocol used. There appears to be no clinical advantage to adding bupivacaine INC. Neither protocol could prevent the development of primary hyperalgesia. PMID- 26870926 TI - A Farewell to Arms. PMID- 26870927 TI - Inheriting a Jewel: A Thrilling Challenge. PMID- 26870928 TI - New Therapeutic Strategies for Primary Sclerosing Cholangitis. AB - Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, which in the majority of patients progresses to liver transplantation or death. To date, no medical treatment has been proven to be of benefit, although ursodeoxycholic acid is widely used. The etiopathogenesis of PSC is unclear, although it is associated with inflammatory bowel disease. Various hypotheses have been suggested, which have led to different therapeutic strategies. Recent studies have suggested that the microbiome may play a role in PSC, raising the possibility of efficacy of antibiotics and fecal microbiota transplantation. Gut homing T cells may be important in the pathogenesis of PSC, and several agents are in development, targeting various receptors, integrins, and ligands on this pathway, including VAP-1, MAdCAM-1, alpha4beta7, and CCR9. Nuclear receptor agonists such as obeticholic acid and fibrates hold promise, as do other therapies that alter bile acid composition such as norUDCA. Antifibrotic agents such as Loxl2 inhibitors are also being assessed. In conclusion, it is likely that an effective drug therapy for PSC will become available over the next decade. PMID- 26870929 TI - Primary Biliary Cirrhosis Beyond Ursodeoxycholic Acid. AB - Although ursodeoxycholic acid remains the only approved pharmacotherapy for patients with primary biliary cirrhosis, the better characterization of factors responsible for the poor response to this drug and the emergence of several new putative therapeutic targets now offer significant opportunities to improve the management of patients and our capacity to treat them more efficiently. The availability of novel treatment options, such as fibrates, budesonide, and obeticholic acid, all capable of improving prognostic markers, invites us to reconsider our management and treatment strategies. Early identification of high risk patients should remain a priority to deliver adjunctive therapies to appropriately selected populations and increase their chances of success. Given the absence of comparative trials, the choice between second-line treatments should be dictated by the biochemical, histological, and expected tolerance profiles. Here the author presents a brief overview of what should be known in this field and proposes a practical approach to facilitate decision making. PMID- 26870931 TI - Targeting Dysbiosis for the Treatment of Liver Disease. AB - The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. PMID- 26870932 TI - Hepatic Encephalopathy: Pharmacological Therapies Targeting Ammonia. AB - Hepatic encephalopathy (HE) is a major complication in patients with decompensated cirrhosis, leading to higher readmission rates causing a profound burden of disease and considerable health care costs. Because ammonia is thought to play a crucial role in the pathogenesis of HE, therapies directed at reducing ammonia levels are now being aggressively developed. Ammonia scavengers such as AST-120 (spherical carbon adsorbent), glycerol phenylbutyrate, sodium phenylacetate or sodium benzoate, and ornithine phenylacetate have been used to improve HE symptoms. A new approach, bowel cleansing with polyethylene glycol 3350, appears to be a promising therapy, with a recent study demonstrating a more rapid improvement in overt HE (at 24 hours after treatment) than lactulose. Extracorporeal devices, although now used primarily in research settings, have also been utilized in patients with refractory HE, but are not approved for clinical management. PMID- 26870930 TI - Targeting Cell Death and Sterile Inflammation Loop for the Treatment of Nonalcoholic Steatohepatitis. AB - Nonalcoholic fatty liver disease represents a wide spectrum of conditions and is currently the most common form of chronic liver disease affecting both adults and children in the United States and many other parts of the world. Great effort has been focused on the development of novel therapies for those patients with the more advanced forms of the disease, in particular those with nonalcoholic steatohepatitis (NASH) and liver fibrosis that can be associated with significant morbidity and mortality. In this review, the authors focus on the role of cell death and sterile inflammatory pathways as well as the self-perpetuating deleterious cycle they may trigger as novel therapeutic targets for the treatment of fibrotic NASH. PMID- 26870933 TI - Therapeutic Strategies for the Treatment of Alcoholic Hepatitis. AB - Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline. Neither of these two drugs impacts medium- and long-term mortality, which is mainly driven by abstinence from alcohol. With the emerging data on the benefits of liver transplantation, liver transplantation could be an important salvage option for a very highly select group of AH patients. More data are needed on the use of liver transplantation in AH as the basis for deriving protocols for selecting cases and for posttransplant management. Currently, many clinical trials are examining the efficacy and safety of new or repurposed compounds in severe AH. These drugs are targeted at various pathways in the pathogenesis of AH: the gut-liver axis, the inflammatory cascade, and liver injury. With increasing interest of researchers and clinicians, supported by funding from the National Institute on Alcohol Abuse and Alcoholism, the future seems promising for the development of effective and safe pharmacological interventions for severe AH. PMID- 26870934 TI - Nuclear Receptor Modulation for the Treatment of Nonalcoholic Fatty Liver Disease. AB - Nuclear receptors (NRs) are ligand-activated transcriptional regulators of several key metabolic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, and energy expenditure as well as inflammation, fibrosis, and cellular proliferation in the liver. Dysregulation of these processes contributes to the pathogenesis and progression of nonalcoholic fatty liver disease (NAFLD). This places NRs at the forefront of novel therapeutic approaches for NAFLD. Some NRs are already pharmacologically targeted in metabolic disorders such as hyperlipidemia (peroxisomal proliferator-activated receptor alpha [PPARalpha], fibrates) and diabetes (PPARgamma, glitazones) with potential applications for NAFLD. Other NRs with potential therapeutic implications are the vitamin D receptor (VDR) and xenobiotic sensors such as constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Further new perspectives include combined ligands for NR isoforms such as PPARalpha/delta ligands. Other novel key players represent the nuclear bile acid receptor farnesoid X receptor (FXR; targeted by synthetic FXR ligands such as obeticholic acid) and RAR-related orphan receptor gamma two (RORgammat). In this review the authors provide an overview of the preclinical and clinical evidence of current and future treatment strategies targeting NRs in metabolism, inflammation, and fibrogenesis of NAFLD. PMID- 26870935 TI - Antifibrotic Therapies: Where Are We Now? AB - Fibrosis is the wound-healing response of tissues to injury. Extensive characterization of organ fibrosis mechanisms has identified common core pathways in renal, pulmonary, skin, and liver fibrosis that offer novel antifibrotic approaches across tissues, in addition to organ-specific and/or disease-specific pathways. A growing number of small molecules and biologics have been identified that are reaching clinical trials for one or more fibrotic diseases, making new antifibrotic options for liver fibrosis an emerging reality. The accelerating pace of drug development, which will also include drug repurposing or combination therapies, heightens the need for novel methods for noninvasive fibrosis assessment without liver biopsy, which is critical to establishing surrogate endpoints for patients in clinical trials who have a low risk of hepatic decompensation. In this article the authors review mechanisms of liver fibrosis and outline potential therapeutic targets and antifibrotic therapies in preclinical studies and clinical trials. PMID- 26870936 TI - An Unusual Cause of Acute Liver Failure: Three Cases of Hemophagocytic Lymphohistiocytosis Presenting at a Transplant Center. AB - Acquired hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disorder of the immune system. Hemophagocytic lymphohistiocytosis has been associated with infections, autoimmune disorders, and malignancy. This case series describes three patients admitted to an academic liver transplant center from February 2014 to February 2015 with acute liver failure (ALF) who were ultimately diagnosed with HLH. All cases were female patients (44 to 53 years of age) transferred for workup of ALF. All developed fevers and cytopenias and underwent rapid evaluation for liver transplant by a multidisciplinary team. A complete workup for ALF was negative for intrinsic liver disease and none had significant alcohol or toxin exposure. The patients had liver biopsies showing diffuse lobular necroinflammation, of which two had evidence of hemophagocytosis on histopathology. The diagnosis of HLH was made by bone marrow biopsy featuring histiocytes with hemophagocytosis. All cases were treated with chemotherapy, but died during their hospitalization. Hemophagocytic lymphohistiocytosis can present as ALF in adult patients. Given the low success rate of treatment, early diagnosis is critical. Therefore, a high degree of suspicion should be exercised in patients with unexplained ALF. PMID- 26870937 TI - Distribution of Ticks and the Risk of Lyme Disease and Other Tick-Borne Pathogens of Public Health Significance in Ontario, Canada. AB - Over the past two decades, the northward spread of Ixodes scapularis across Ontario, Canada, has accelerated and the risk of Lyme disease has increased. Active surveillance is a recognized and effective method for detecting reproducing populations of I. scapularis. In this study, we conducted field sampling consistent with an active surveillance approach from May to October 2014 at 104 sites in central, eastern, and southern Ontario to determine the current distribution of I. scapularis and other tick species, and enhance our understanding of the geographic risk associated with Borrelia burgdorferi and other tick-borne pathogens of public health significance in this region. I. scapularis was present at 20 of the 104 sites visited. Individuals of the tick species Dermacentor variabilis, Haemaphysalis leporispalustris, and Ixodes dentatus were also collected. I. scapularis was positive by PCR for B. burgdorferi at five sites. These sites formed a significant spatial cluster in eastern Ontario. No ticks were PCR positive for Borrelia miyamotoi, Anaplasma phagocytophilum, and Babesia microti. This study provides an up-to-date picture of the distribution of I. scapularis and other tick species, and the risk of B. burgdorferi and other pathogens of public health significance in central, eastern, and southern Ontario. This information may allow for more effective surveillance efforts and public health interventions for Lyme disease and other tick-borne diseases in this region. PMID- 26870938 TI - From evoked potentials to cortical currents: Resolving V1 and V2 components using retinotopy constrained source estimation without fMRI. AB - Despite evoked potentials' (EP) ubiquity in research and clinical medicine, insights are limited to gross brain dynamics as it remains challenging to map surface potentials to their sources in specific cortical regions. Multiple sources cancellation due to cortical folding and cross-talk obscures close sources, e.g. between visual areas V1 and V2. Recently retinotopic functional magnetic resonance imaging (fMRI) responses were used to constrain source locations to assist separating close sources and to determine cortical current generators. However, an fMRI is largely infeasible for routine EP investigation. We developed a novel method that replaces the fMRI derived retinotopic layout (RL) by an approach where the retinotopy and current estimates are generated from EEG or MEG signals and a standard clinical T1-weighted anatomical MRI. Using the EEG-RL, sources were localized to within 2 mm of the fMRI-RL constrained localized sources. The EEG-RL also produced V1 and V2 current waveforms that closely matched the fMRI-RL's (n = 2) r(1,198) = 0.99, P < 0.0001. Applying the method to subjects without fMRI (n = 4) demonstrates it generates waveforms that agree closely with the literature. Our advance allows investigators with their current EEG or MEG systems to create a library of brain models tuned to individual subjects' cortical folding in retinotopic maps, and should be applicable to auditory and somatosensory maps. The novel method developed expands EP's ability to study specific brain areas, revitalizing this well-worn technique. Hum Brain Mapp 37:1696-1709, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26870939 TI - Nuclear energy and biodiversity conservation: response to Brook and Bradshaw 2015. PMID- 26870940 TI - Catalytic Response and Stability of Nickel/Alumina for the Hydrogenation of 5 Hydroxymethylfurfural in Water. AB - The catalytic response of Ni on Al2O3 obtained from Ni-Al layered double hydroxides was studied for the liquid-phase hydrogenation of hydroxymethyl furfural to tetrahydrofuran-2,5-diyldimethanol (THFDM) in water. The successive calcination and reduction of the precursors caused the removal of interlayer hydroxyl and carbonate groups and the reduction of Ni(2+) to Ni(0). Four reduced mixed oxide catalysts were obtained, consisting of different amount of Ni metal contents (47-68 wt%) on an Al-rich amorphous component. The catalytic activity was linked to Ni content whereas selectivity was mainly affected by reaction temperature. THFDM was formed in a stepwise manner at low temperature (353 K) whereas 3-hydroxymethyl cyclopentanone was generated at higher temperature. Coke formation caused deactivation; however, the catalytic activity can be regenerated using heat treatment. The results establish Ni on Al2O3 as a promising catalyst for the production of THFDM in water. PMID- 26870941 TI - Development of a Topical Treatment for Psoriasis Targeting RORgamma: From Bench to Skin. AB - BACKGROUND: Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies. Thus, for the majority of psoriasis patients ineligible for systemic treatments, a small molecule targeting RORgammat, the master regulator of IL-17 family cytokines, may represent an alternative topical medicine with biologic-like efficacy. METHODS AND FINDINGS: The preclinical studies described in this manuscript bridge the gap from bench to bedside to provide the scientific foundation for a compound entering clinical trials for patients with mild to moderate psoriasis. In addition to several ex vivo reporter assays, primary T cell cultures, and the imiquimod mouse model, we demonstrate efficacy in a newly developed human ex vivo skin assay, where Th17 skewed cytokine expression is induced from skin-resident immune cells. Importantly, the skin barrier remains intact allowing for the demonstration of topical drug delivery. With the development of this novel assay, we demonstrate potent compound activity in the target tissue: human skin. Finally, target engagement by this small molecule was confirmed in ex vivo lesional psoriatic skin. CONCLUSIONS: Our work describes a progressive series of assays to demonstrate the potential clinical value of a novel RORgamma inverse agonist small molecule with high potency and selectivity, which will enter clinical trials in late 2015 for psoriasis patients. PMID- 26870942 TI - Lithium Ameliorates LPS-Induced Astrocytes Activation Partly via Inhibition of Toll-Like Receptor 4 Expression. AB - BACKGROUND/AIMS: Astrocytes are critical for the development of postoperative cognitive dysfunction (POCD). In addition, astrocytes express toll-like receptors 4 (TLR4) and build up responses to innate immune triggers by releasing pro inflammatory molecules. The pathogenesis of neurological disorders often involves the activation of astrocytes and associated inflammatory processes. Lithium, a primary drug for the treatment of bipolar disorder, has recently been suggested to have a role in neuroprotection during neurodegenerative diseases. In this study, we aimed to investigate whether lithium can ameliorate LPS-induced astrocytes activation via inhibition of TLR4 expression. METHODS: Primary astrocytes cells were pretreated with lithium and stimulated with lipopolysaccharide (LPS). Cellular activation, cytokine production, and TLR4 expression, were assessed. RESULTS: Lithium significantly inhibited LPS-induced astrocytes activation and pro-inflammatory cytokine production, as well as LPS induced TLR4 expression. CONCLUSIONS: Lithium can inhibit LPS-induced TLR4 expression and astrocytes activation. These results indicate that lithium plays an important role in astrocytes activation and neuroinflammation-related diseases, which may open new avenues for neuroscience and biomedical research, and also offers new insight into the treatment of POCD. PMID- 26870943 TI - The Subjective Sensation of Synchrony: An Experimental Study. AB - People performing actions together have a natural tendency to synchronize their behavior. Consistently, people doing a task together build internal representations not only of their actions and goals, but also of the other people performing the task. However, little is known about which are the behavioral mechanisms and the psychological factors affecting the subjective sensation of synchrony, or "connecting" with someone else. In this work, we sought to find which factors induce the subjective sensation of synchrony, combining motion capture data and psychological measures. Our results show that the subjective sensation of synchrony is affected by performance quality together with task category, and time. Psychological factors such as empathy and negative subjective affects also correlate with the subjective sensation of synchrony. However, when people estimate synchrony as seen from a third person perspective, their psychological factors do not affect the accuracy of the estimation. We suggest that to feel this sensation it is necessary to, first, have a good joint performance and, second, to assume the existence of an attention monitoring mechanism that reports that the attention of both participants (self and other) is focused on the task. PMID- 26870945 TI - Probing the Catalytic Mechanism of Vibrio harveyi GH20 beta-N Acetylglucosaminidase by Chemical Rescue. AB - BACKGROUND: Vibrio harveyi GH20 beta-N-acetylglucosaminidase (VhGlcNAcase) is a chitinolytic enzyme responsible for the successive degradation of chitin fragments to GlcNAc monomers, activating the onset of the chitin catabolic cascade in marine Vibrios. METHODS: Two invariant acidic pairs (Asp303-Asp304 and Asp437-Glu438) of VhGlcNAcase were mutated using a site-directed mutagenesis strategy. The effects of these mutations were examined and the catalytic roles of these active-site residues were elucidated using a chemical rescue approach. Enhancement of the enzymic activity of the VhGlcNAcase mutants was evaluated by a colorimetric assay using pNP-GlcNAc as substrate. RESULTS: Substitution of Asp303, Asp304, Asp437 or Glu438 with Ala/Asn/Gln produced a dramatic loss of the GlcNAcase activity. However, the activity of the inactive D437A mutant was recovered in the presence of sodium formate. Our kinetic data suggest that formate ion plays a nucleophilic role by mimicking the beta-COO-side chain of Asp437, thereby stabilizing the reaction intermediate during both the glycosylation and the deglycosylation steps. CONCLUSIONS: Chemical rescue of the inactive D437A mutant of VhGlcNAcase by an added nucleophile helped to identify Asp437 as the catalytic nucleophile/base, and hence its acidic partner Glu438 as the catalytic proton donor/acceptor. GENERAL SIGNIFICANCE: Identification of the catalytic nucleophile of VhGlcNAcases supports the proposal of a substrate assisted mechanism of GH20 GlcNAcases, requiring the catalytic pair Asp437-Glu438 for catalysis. The results suggest the mechanistic basis of the participation of beta-N-acetylglucosaminidase in the chitin catabolic pathway of marine Vibrios. PMID- 26870944 TI - Luteoloside Acts as 3C Protease Inhibitor of Enterovirus 71 In Vitro. AB - Luteoloside is a member of the flavonoids family that exhibits several bioactivities including anti-microbial and anti-cancer activities. However, the antiviral activity of luteoloside against enterovirus 71 (EV71) and the potential mechanism(s) responsible for this effect remain unknown. In this study, the antiviral potency of luteoloside against EV71 and its inhibitory effects on 3C protease activity were evaluated. First, we investigated the cytotoxicity of luteoloside against rhabdomyosarcoma (RD) cells, which was the cell line selected for an in vitro infection model. In a subsequent antiviral assay, the cytopathic effect of EV71 was significantly and dose-dependently relieved by the administration of luteoloside (EC50 = 0.43 mM, selection index = 5.3). Using a plaque reduction assay, we administered luteoloside at various time points and found that the compound reduced EV71 viability in RD cells rather than increasing defensive mobilization or viral absorption. Moreover, biochemical studies focused on VP1 (a key structural protein of EV71) mRNA transcript and protein levels also revealed the inhibitory effects of luteoloside on the EV71 viral yield. Finally, we performed inhibition assays using luteoloside to evaluate its effect on recombinant 3C protease activity. Our results demonstrated that luteoloside blocked 3C protease enzymatic activity in a dose-dependent manner (IC50 = 0.36 mM) that was similar to the effect of rutin, which is a well-known C3 protease inhibitor. Collectively, the results from this study indicate that luteoloside can block 3C protease activity and subsequently inhibit EV71 production in vitro. PMID- 26870946 TI - Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy. AB - BACKGROUND: The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia. FINDINGS: We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters. CONCLUSION: The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies. PMID- 26870947 TI - Charged Molecules Modulate the Volume Exclusion Effects Exerted by Crowders on FtsZ Polymerization. AB - We have studied the influence of protein crowders, either combined or individually, on the GTP-induced FtsZ cooperative assembly, crucial for the formation of the dynamic septal ring and, hence, for bacterial division. It was earlier demonstrated that high concentrations of inert polymers like Ficoll 70, used to mimic the crowded cellular interior, favor the assembly of FtsZ into bundles with slow depolymerization. We have found, by fluorescence anisotropy together with light scattering measurements, that the presence of protein crowders increases the tendency of FtsZ to polymerize at micromolar magnesium concentration, being the effect larger with ovomucoid, a negatively charged protein. Neutral polymers and a positively charged protein also diminished the critical concentration of assembly, the extent of the effect being compatible with that expected according to pure volume exclusion models. FtsZ polymerization was also observed to be strongly promoted by a negatively charged polymer, DNA, and by some unrelated polymers like PEGs at concentrations below the crowding regime. The influence of mixed crowders mimicking the heterogeneity of the intracellular environment on the tendency of FtsZ to assemble was also studied and nonadditive effects were found to prevail. Far from exactly reproducing the bacterial cytoplasm environment, this approach serves as a simplified model illustrating how its intrinsically crowded and heterogeneous nature may modulate FtsZ assembly into a functional Z-ring. PMID- 26870948 TI - Artificial Saliva Formulations versus Human Saliva Pretreatment in Dental Erosion Experiments. AB - The aim of this study was to evaluate the erosion-preventive effect of different artificial saliva formulations and human saliva in vitro compared to human saliva in situ. In the in vitro experiment, bovine enamel and dentin specimens were stored in artificial saliva (4 different formulations, each n = 20), deionized water (n = 20) or human saliva (n = 6 enamel and dentin specimens/volunteer) for 120 min. In the in situ experiment, each of the 6 enamel and dentin specimens was worn intraorally by 10 volunteers for 120 min. The specimens were then eroded (HCl, pH 2.6, 60 s). Half of the specimens were subjected to microhardness analysis (enamel) and the determination of calcium release into the acid (enamel and dentin), while the other half were again placed in the respective medium or worn intraorally, respectively, for 120 min before a second erosion was performed. Knoop microhardness of enamel and the calcium release of enamel and dentin into the acid were again determined. Statistical analysis was conducted by two-way repeated-measures ANOVA or two-way ANOVA (alpha = 0.05). Enamel microhardness was not significantly different between all test groups after the first and the second erosive challenge, respectively. Enamel calcium loss was significantly lower in situ compared to the in vitro experiment, where there was no significant difference between all test groups. Dentin calcium loss was significantly lower than deionized water only after the first and than all except one artificial saliva after the second erosion. Under the conditions of this experiment, the use of artificial saliva formulations and human saliva in vitro does not reflect the intraoral situation in dental erosion experiments adequately. PMID- 26870949 TI - RV-Typer: A Web Server for Typing of Rhinoviruses Using Alignment-Free Approach. AB - Rhinoviruses (RV) are increasingly being reported to cause mild to severe infections of respiratory tract in humans. RV are antigenically the most diverse species of the genus Enterovirus and family Picornaviridae. There are three species of RV (RV-A, -B and -C), with 80, 32 and 55 serotypes/types, respectively. Antigenic variation is the main limiting factor for development of a cross-protective vaccine against RV.Serotyping of Rhinoviruses is carried out using cross-neutralization assays in cell culture. However, these assays become laborious and time-consuming for the large number of strains. Alternatively, serotyping of RV is carried out by alignment-based phylogeny of both protein and nucleotide sequences of VP1. However, serotyping of RV based on alignment-based phylogeny is a multi-step process, which needs to be repeated every time a new isolate is sequenced. In view of the growing need for serotyping of RV, an alignment-free method based on "return time distribution" (RTD) of amino acid residues in VP1 protein has been developed and implemented in the form of a web server titled RV-Typer. RV-Typer accepts nucleotide or protein sequences as an input and computes return times of di-peptides (k = 2) to assign serotypes. The RV-Typer performs with 100% sensitivity and specificity. It is significantly faster than alignment-based methods. The web server is available at http://bioinfo.net.in/RV-Typer/home.html. PMID- 26870951 TI - Correction: Niger's Child Survival Success, Contributing Factors and Challenges to Sustainability: A Retrospective Analysis. PMID- 26870950 TI - Intra-Aortic Balloon Pump Counterpulsation during Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction and Cardiogenic Shock: Insights from the British Columbia Cardiac Registry. AB - BACKGROUND: Cardiogenic shock complicating ST-elevation myocardial infarction (STEMI) is associated with significant morbidity and mortality. In the primary percutaneous coronary intervention (PPCI) era, randomized trials have not shown a survival benefit with intra-aortic balloon pump (IABP) therapy. This differs to observational data which show a detrimental effect, potentially reflecting bias and confounding. Without robust and valid risk adjustment, findings from non randomized studies may remain biased. METHODS: We compared long-term mortality following IABP therapy in patients with cardiogenic shock undergoing PPCI during 2008-2013 from the British Columbia Cardiac Registry. We addressed measured and unmeasured confounding using propensity score and instrumental variable methods. RESULTS: A total of 12,105 patients with STEMI were treated with PPCI during the study period. Of these, 700 patients (5.8%) had cardiogenic shock. Of the patients with cardiogenic shock, 255 patients (36%) received IABP therapy. Multivariable analyses identified IABP therapy to be associated with increased mortality up to 3 years (HR = 1.67, 95% CI:1.20-2.67, p<0.001). This association was lost in propensity-matched analyses (HR = 1.23, 95% CI: 0.84-1.80, p = 0.288). When addressing measured and unmeasured confounders, instrumental variable analyses demonstrated that IABP therapy was not associated with mortality at 3 years (Delta = 16.7%, 95% CI: -12.7%, 46.1%, p = 0.281). Subgroup analyses demonstrated IABP was associated with increased mortality in non diabetics; patients not undergoing multivessel intervention; patients without renal disease and patients not having received prior thrombolysis. CONCLUSIONS: In this observational analysis of patients with STEMI and cardiogenic shock, when adjusting for confounding, IABP therapy had a neutral effect with no association with long-term mortality. These findings differ to previously reported observational studies, but are in keeping with randomized trial data. PMID- 26870953 TI - Anterior Corticospinal Tract Revisited: A Study Using Human Fetuses. AB - In the human corticospinal tract (CST), the anterior CST is known to be much thinner than the lateral CST, but fetal development of the CST remains obscure. In this study, we examined horizontal histological sections of the cervical spinal cord from 50 midterm fetuses (crown-rump length, CRL, 70-150 mm; 12-18 weeks) as well as 15 late-stage fetuses (CRL 230-250 mm; 28-30 weeks). While the lateral CST appeared at 14-15 weeks in the cervical cord of the midterm fetuses, we found the anterior CST in only 3 fetuses: CRL 117 mm (15 weeks), and CRL 144 and 150 mm (18 weeks). However, in the late-stage fetuses, the anterior CST exhibited a spectrum of variations, including bilaterally thick tracts (3 fetuses), a unilaterally thick tract (5 fetuses) and a thin or absent tract (7 fetuses). In the group with the thickest anterior CST, the cross-sectional area reached 40% of that of the lateral CST. In contrast to the stable morphology of the lateral CST, the shape of the anterior tract varied slightly between the cervical segments. Immunohistochemical observations demonstrated no difference between the lateral and anterior CSTs: (1) in macrophage infiltration, which suggests apoptosis, and (2) in the arrangement of radial glial fibers. Our findings indicate that the development of the anterior CST starts later than that of the lateral tract, with significant individual variations. The functional relevance of the anterior CST, if present, might not be found in an independent cortical input to motor neurons but in a remodeling of the ascending tracts. PMID- 26870952 TI - Muscle Logic: New Knowledge Resource for Anatomy Enables Comprehensive Searches of the Literature on the Feeding Muscles of Mammals. AB - BACKGROUND: In recent years large bibliographic databases have made much of the published literature of biology available for searches. However, the capabilities of the search engines integrated into these databases for text-based bibliographic searches are limited. To enable searches that deliver the results expected by comparative anatomists, an underlying logical structure known as an ontology is required. DEVELOPMENT AND TESTING OF THE ONTOLOGY: Here we present the Mammalian Feeding Muscle Ontology (MFMO), a multi-species ontology focused on anatomical structures that participate in feeding and other oral/pharyngeal behaviors. A unique feature of the MFMO is that a simple, computable, definition of each muscle, which includes its attachments and innervation, is true across mammals. This construction mirrors the logical foundation of comparative anatomy and permits searches using language familiar to biologists. Further, it provides a template for muscles that will be useful in extending any anatomy ontology. The MFMO is developed to support the Feeding Experiments End-User Database Project (FEED, https://feedexp.org/), a publicly-available, online repository for physiological data collected from in vivo studies of feeding (e.g., mastication, biting, swallowing) in mammals. Currently the MFMO is integrated into FEED and also into two literature-specific implementations of Textpresso, a text-mining system that facilitates powerful searches of a corpus of scientific publications. We evaluate the MFMO by asking questions that test the ability of the ontology to return appropriate answers (competency questions). We compare the results of queries of the MFMO to results from similar searches in PubMed and Google Scholar. RESULTS AND SIGNIFICANCE: Our tests demonstrate that the MFMO is competent to answer queries formed in the common language of comparative anatomy, but PubMed and Google Scholar are not. Overall, our results show that by incorporating anatomical ontologies into searches, an expanded and anatomically comprehensive set of results can be obtained. The broader scientific and publishing communities should consider taking up the challenge of semantically enabled search capabilities. PMID- 26870955 TI - Benevolent Ideology and Women's Economic Decision-Making: When Sexism Is Hurting Men's Wallet. AB - Can ideology, as a widespread "expectation creator," impact economic decisions? In two studies we investigated the influence of the Benevolent Sexism (BS) ideology (which dictates that men should provide for passive and nurtured women) on women's economic decision-making. In Study 1, using a Dictator Game in which women decided how to share amounts of money with men, results of a Generalized Linear Mixed Model analysis show that higher endorsement of BS and contextual expectations of benevolence were associated with more very unequal offers. Similarly, in an Ultimatum Game in which women received monetary offers from men, Study 2's Generalized Linear Mixed Model's results revealed that BS led women to reject more very unequal offers. If women's endorsement of BS ideology and expectations of benevolence prove contrary to reality, they may strike back at men. These findings show that BS ideology creates expectations that shape male female relationships in a way that could be prejudicial to men. PMID- 26870954 TI - A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice. AB - The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method. PMID- 26870956 TI - Meta-Analysis of Tumor Stem-Like Breast Cancer Cells Using Gene Set and Network Analysis. AB - Generally, cancer stem cells have epithelial-to-mesenchymal-transition characteristics and other aggressive properties that cause metastasis. However, there have been no confident markers for the identification of cancer stem cells and comparative methods examining adherent and sphere cells are widely used to investigate mechanism underlying cancer stem cells, because sphere cells have been known to maintain cancer stem cell characteristics. In this study, we conducted a meta-analysis that combined gene expression profiles from several studies that utilized tumorsphere technology to investigate tumor stem-like breast cancer cells. We used our own gene expression profiles along with the three different gene expression profiles from the Gene Expression Omnibus, which we combined using the ComBat method, and obtained significant gene sets using the gene set analysis of our datasets and the combined dataset. This experiment focused on four gene sets such as cytokine-cytokine receptor interaction that demonstrated significance in both datasets. Our observations demonstrated that among the genes of four significant gene sets, six genes were consistently up regulated and satisfied the p-value of < 0.05, and our network analysis showed high connectivity in five genes. From these results, we established CXCR4, CXCL1 and HMGCS1, the intersecting genes of the datasets with high connectivity and p value of < 0.05, as significant genes in the identification of cancer stem cells. Additional experiment using quantitative reverse transcription-polymerase chain reaction showed significant up-regulation in MCF-7 derived sphere cells and confirmed the importance of these three genes. Taken together, using meta analysis that combines gene set and network analysis, we suggested CXCR4, CXCL1 and HMGCS1 as candidates involved in tumor stem-like breast cancer cells. Distinct from other meta-analysis, by using gene set analysis, we selected possible markers which can explain the biological mechanisms and suggested network analysis as an additional criterion for selecting candidates. PMID- 26870957 TI - The Epigenomic Landscape of Prokaryotes. AB - DNA methylation acts in concert with restriction enzymes to protect the integrity of prokaryotic genomes. Studies in a limited number of organisms suggest that methylation also contributes to prokaryotic genome regulation, but the prevalence and properties of such non-restriction-associated methylation systems remain poorly understood. Here, we used single molecule, real-time sequencing to map DNA modifications including m6A, m4C, and m5C across the genomes of 230 diverse bacterial and archaeal species. We observed DNA methylation in nearly all (93%) organisms examined, and identified a total of 834 distinct reproducibly methylated motifs. This data enabled annotation of the DNA binding specificities of 620 DNA Methyltransferases (MTases), doubling known specificities for previously hard to study Type I, IIG and III MTases, and revealing their extraordinary diversity. Strikingly, 48% of organisms harbor active Type II MTases with no apparent cognate restriction enzyme. These active 'orphan' MTases are present in diverse bacterial and archaeal phyla and show motif specificities and methylation patterns consistent with functions in gene regulation and DNA replication. Our results reveal the pervasive presence of DNA methylation throughout the prokaryotic kingdoms, as well as the diversity of sequence specificities and potential functions of DNA methylation systems. PMID- 26870958 TI - Sensitive Detection of Plasmodium vivax Using a High-Throughput, Colourimetric Loop Mediated Isothermal Amplification (HtLAMP) Platform: A Potential Novel Tool for Malaria Elimination. AB - INTRODUCTION: Plasmodium vivax malaria has a wide geographic distribution and poses challenges to malaria elimination that are likely to be greater than those of P. falciparum. Diagnostic tools for P. vivax infection in non-reference laboratory settings are limited to microscopy and rapid diagnostic tests but these are unreliable at low parasitemia. The development and validation of a high throughput and sensitive assay for P. vivax is a priority. METHODS: A high throughput LAMP assay targeting a P. vivax mitochondrial gene and deploying colorimetric detection in a 96-well plate format was developed and evaluated in the laboratory. Diagnostic accuracy was compared against microscopy, antigen detection tests and PCR and validated in samples from malaria patients and community controls in a district hospital setting in Sabah, Malaysia. RESULTS: The high throughput LAMP-P. vivax assay (HtLAMP-Pv) performed with an estimated limit of detection of 1.4 parasites/ MUL. Assay primers demonstrated cross reactivity with P. knowlesi but not with other Plasmodium spp. Field testing of HtLAMP-Pv was conducted using 149 samples from symptomatic malaria patients (64 P. vivax, 17 P. falciparum, 56 P. knowlesi, 7 P. malariae, 1 mixed P. knowlesi/P. vivax, with 4 excluded). When compared against multiplex PCR, HtLAMP-Pv demonstrated a sensitivity for P. vivax of 95% (95% CI 87-99%); 61/64), and specificity of 100% (95% CI 86-100%); 25/25) when P. knowlesi samples were excluded. HtLAMP-Pv testing of 112 samples from asymptomatic community controls, 7 of which had submicroscopic P. vivax infections by PCR, showed a sensitivity of 71% (95% CI 29-96%; 5/7) and specificity of 93% (95% CI87-97%; 98/105). CONCLUSION: This novel HtLAMP-P. vivax assay has the potential to be a useful field applicable molecular diagnostic test for P. vivax infection in elimination settings. PMID- 26870959 TI - Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting. AB - BACKGROUND AND PURPOSE: Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes. METHODS: Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients. RESULTS: A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03 2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10-3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12-3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events. CONCLUSIONS: PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events. PMID- 26870960 TI - EPICE-HIV: An Epidemiologic Cost-Effectiveness Model for HIV Treatment. AB - The goal of this research was to establish a new and innovative framework for cost-effectiveness modeling of HIV-1 treatment, simultaneously considering both clinical and epidemiological outcomes. EPICE-HIV is a multi-paradigm model based on a within-host micro-simulation model for the disease progression of HIV-1 infected individuals and an agent-based sexual contact network (SCN) model for the transmission of HIV-1 infection. It includes HIV-1 viral dynamics, CD4+ T cell infection rates, and pharmacokinetics/pharmacodynamics modeling. Disease progression of HIV-1 infected individuals is driven by the interdependent changes in CD4+ T cell count, changes in plasma HIV-1 RNA, accumulation of resistance mutations and adherence to treatment. The two parts of the model are joined through a per-sexual-act and viral load dependent probability of disease transmission in HIV-discordant couples. Internal validity of the disease progression part of the model is assessed and external validity is demonstrated in comparison to the outcomes observed in the STaR randomized controlled clinical trial. We found that overall adherence to treatment and the resulting pattern of treatment interruptions are key drivers of HIV-1 treatment outcomes. Our model, though largely independent of efficacy data from RCT, was accurate in producing 96-week outcomes, qualitatively and quantitatively comparable to the ones observed in the STaR trial. We demonstrate that multi-paradigm micro-simulation modeling is a promising tool to generate evidence about optimal policy strategies in HIV-1 treatment, including treatment efficacy, HIV-1 transmission, and cost effectiveness analysis. PMID- 26870962 TI - Elevated Toll-Like Receptor-Induced CXCL8 Secretion in Human Blood Basophils from Allergic Donors Is Independent of Toll-Like Receptor Expression Levels. AB - Human blood basophils have recently gained interest in addition to their function as allergic effector cells. Previous work suggests the involvement of innate immune mechanisms in the development and exacerbation of allergic responses, which might be mediated by basophils. We assayed the expression levels of Toll like receptor (TLR) 1, 2, 4 and 6 on purified basophils from birch pollen-, house dust mite-, and non-allergic individuals. Additionally, we compared cytokine and chemokine secretion upon TLR stimulation in these basophil donor groups. Expression of TLR4 on the basophils of the allergic donor groups was decreased and CXCL8 secretion was elevated upon stimulation of TLR1/2 and TLR2/6 compared to the non-allergic donors. Decreased TLR expression and elevated CXCL8 secretion may represent possible mechanisms for aggravation of allergic symptoms in case of parasitic infection. PMID- 26870961 TI - Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair. AB - Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression. PMID- 26870964 TI - Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients. AB - AIMS/INTRODUCTION: Irisin is a newly identified myokine which can promote energy expenditure. Urotensin II (UII) is identified as the most potent mammalian vasoconstrictor to date. Previous studies showed that UII can aggravate insulin resistance while irisin alleviate insulin resistance. Through this study, it is our aim to elucidate if UII can induce insulin resistance and also have an association with the irisin level in hemodialysis (HD) patients. MATERIALS AND METHODS: One hundred and twenty-eight patients on maintenance hemodialysis treatment and forty healthy subjects were enrolled in this study. Blood irisin concentrations and UII concentrations were measured by ELISA and RIA respectively. The body composition was analyzed by bioelectrical impedance. RESULTS: The serum irisin levels and UII levels were both significantly lower in HD patients in comparison to that of the healthy subjects. The serum irisin levels were lower in HD patients with protein energy wasting than those of the patients without protein energy wasting. The independent determinants of circulating Ln (irisin) (the natural logarithm of irisin) were UII lean body mass and patients with protein energy wasting. CONCLUSIONS: Our results are the first to provide the clinical evidence of the association among irisin, UII, and protein energy wasting. Our results hint that UII and protein energy wasting might inhibit the release or synthesis of irisin from skeletal muscles in HD patients. PMID- 26870963 TI - Do Case Rates Affect Physicians' Clinical Practice in Radiation Oncology?: An Observational Study. AB - Case rate payments combined with utilization monitoring may have the potential to improve the quality of care by reducing over and under-treatment. Thus, a national managed care organization introduced case rate payments at one multi site radiation oncology provider while maintaining only fee-for-service payments at others. This study examined whether the introduction of the payment method had an effect on radiation fractions administered when compared to clinical guidelines. The number of fractions of radiation therapy delivered to patients with bone metastases, breast, lung, prostate, and skin cancer was assessed for concordance with clinical guidelines. The proportion of guideline-based care ascertained from the payer's claims database was compared before (2011) and after (2013) the payment method introduction using relative risks (RR). After the introduction of case rates, there were no significant changes in guideline-based care in breast, lung, and skin cancer; however, patients with bone metastases and prostate cancer were significantly more likely to have received guideline-based care (RR = 2.0 and 1.1, respectively, p<0.05). For the aggregate of all cancers, the under-treatment rate significantly declined (p = 0.008) from 4% to 0% after the introduction of case rate payments, while the over-treatment rate remained steady at 9%, with no significant change (p = 0.20). These findings suggest that the introduction of case rate payments did not adversely affect the rate of guideline-based care at the provider examined. Additional research is needed to isolate the effect of the payment model and assess implications in other populations. PMID- 26870967 TI - Correction: A Two-Stage Algorithm for Origin-Destination Matrices Estimation Considering Dynamic Dispersion Parameter for Route Choice. PMID- 26870966 TI - A Generic Mechanism for Enhanced Cytokine Signaling via Cytokine-Neutralizing Antibodies. AB - Enhancement or inhibition of cytokine signaling and corresponding immune cells responses are critical factors in various disease treatments. Cytokine signaling may be inhibited by cytokine-neutralizing antibodies (CNAs), which prevents further activation of cytokine receptors. However, CNAs may result in enhanced instead of inhibitory-cytokine signaling (an "agonistic effect") in various in vitro and in vivo experiments. This may lead to lack of efficacy or adverse events for cytokine-inhibiting based medicines. Alternatively, cytokine-antibody complexes may produce stronger signaling vs. cytokine alone, thereby increasing the efficacy of stimulating cytokine-based drugs, at equal or lower cytokine doses. In this paper, the effect of cytokine signaling enhancement by a CNA was studied in a generic mathematical model of interleukin-4 (IL-4) driven T-cell proliferation. The occurrence of the agonistic effect depends upon the antibody to-cytokine binding affinity and initial concentrations of antibody and cytokine. Model predictions were in agreement with experimental studies. When the cytokine receptor consists of multiple subunits with substantially differing affinities (e.g., IL-4 case), the choice of the receptor chain to be blocked by the antibody is critical, for the agonistic effect to appear. We propose a generic mechanism for the effect: initially, binding of the CNA to the cytokine reduces free cytokine concentration; yet, cytokine molecules bound within the cytokine-CNA complex-and released later and over time-are "rescued" from earlier clearance via cellular internalization. Hence, although free cytokine-dependent signalling may be less potent initially, it will also be more sustained over time; and given non linear dynamics, it will lead ultimately to larger cellular effector responses, vs. the same amount of free cytokine in the absence of CNA. We suggest that the proposed mechanism is a generic property of {cytokine, CNA, receptor} triads, both in vitro and in vivo, and can occur in a predictable fashion for a variety of cytokines of the immune system. PMID- 26870965 TI - Impact of Increasing Dietary Calcium Levels on Calcium Excretion and Vitamin D Metabolites in the Blood of Healthy Adult Cats. AB - BACKGROUND: Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. RESULTS: Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D2 and 25(OH)D3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). CONCLUSIONS: In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P. PMID- 26870968 TI - [ULTRASOUND MONITORING FEATURES OF POSTOPERATIVE HEPATIC ECHINOCOCCOSIS]. AB - The aim of the study was to investigate ultrasound features (US) of liver after post operative anti-parasite recurrence treatment of patients with echinococcosis. The clinical analyses of 50 patients were carried out. It was concluded that the use of ultrasound can provide valuable data to the clinician to assess and monitor anti parasitic therapy echinococcosis of liver in post operative period. During the monitoring the positive dynamics of disease was observed in 94,5% of cases, in 5% of cases toxic hepatites with septic complication was diagnosed, and in 0,5% of cases the disease recurrence was revealed. Ultrasound semiotics of liver after post operative anti-parasite recurrence treatment of patients with echinococcosis was presented. Control and monitoring of patients in the postoperative period echinococcosis with appropriate antirelapse antiparasitic therapy should be held not less than 1-5 years. PMID- 26870969 TI - EFFECT OF SMOKING ON TRASIENTLY EVOKED OTOACOUSTIC EMISSION. AB - Evoked otoacoustic emissions, EOAEs, are proved to be sounds aroused in response to external acoustic stimulus by the cochlear outer hair cells. Transiently evoked otoacoustic emissions, TEOAEs, are the most clinically utilized EOAEs. TEOAEs are detectable in 98% of people with normal hearing, regardless of age or sex, while two ears of any individual produce similar TEOAEs waveforms. The objective of the presented study was the comparison of TEOAE magnitudes in cigarette smokers and nonsmokers. The TEOAE occurrence and characteristics in individuals of both samples with audiometrically proved hearing losses and in those without were also specifically examined. 30 smokers and and 30 nonsmokers within the age range of 30-59 years were involved in the present study after informed concent. OAEs were performed to each subject by Madsen Capella's OAE/middle ear analyzer-GN Otometrics, (Danmark). After OAE testing each subject was performed routine pure-tone audiometry and tympanometry. Obtained results were statistically treated by the student's t-distribution. According to our results 76.6% of smokers and 3.33% of nonsmokers had marked different level decrease in TEOAE amplitude. Audiographic measurments showed altered audiogram in 6.7% of smokers and in 3.33% of nonsmokers. Based on the above mentioned results we suppose that smoking has significant influence on hearing function, especially on cochlear apparatus; At the same time, TOEAE, as a sensitive method can be used for very early detection of hearing loss, even when there are neither any subjective complains nor some changies on audiogram. PMID- 26870971 TI - IMAGING GUIDED PERCUTANEAL CORE BIOPSY OF PULMONARY AND PLEURAL MASSES - TECHNIQUE AND COMPLICATIONS. AB - Paper presents the ultrasound (US) and computed tomography (CT) guided percutaneous lung core biopsy technique and procedure associated complications. 148 percutaneous biopsies of lung and peural lesions were performed in 143 patients ( in 5 (3.4%) cases the repeated procedure was needed). Procedure was guided by US in 42 cases, by CT - in 106 cases. Post-biopsy CT scan was performed and patients observed for any complications. No complications were detected after US guided procedures; No major complications were detected after CT guided biopsy procedures; minor complications (pneumothorax, hemothorax and hemophtysis) were detected in 24 (22.6%) cases. In 18 (17.0%) cases pneumothorax, in 1 (0/9%) cases - hemothorax and in 5 (4.7%) cases hemophtisis was detected on CT guided procedures. All hemothorax and hemophtisis and 13(12.3%) pneumothorax cases happened to be self-limited; in 3(2.8%) pneumothorax cases aspiration and in 2(1.9%) cases - pleural drainage was needed. Ultrasound is the most efficient for biopsy guidance if the "target" can be adequately imaged by this technique. If US guidance is impossible biopsy should be performed under CT guidance. Pneumothorax and hemothoraxs was associated with multiple needle passes, lesion diameter <2 cm and larger diameter needle use. Hemoptysis was not associated with multiple needle passes, lesioan size and larger diameter needle. No air embolism was detected on our study. The safety and biopsy procedure success high rate proves the use of imaging guided percutaneal core biopsy of pulmonary and pleural masses as a first choice procedure when the lung or pleural mass morphology is needed. PMID- 26870970 TI - IMAGING GUIDED PERCUTANEAL CORE BIOPSY OF THORACIC BONE AND SOFT TISSUE LESIONS - TECHNIQUE AND COMPLICATIONS. AB - The purpose of the paper is to present our experience of Imaging Guided Percutaneal Core Biopsy (IGPCB) of thoracic bone and soft tissue lesions in terms of procedure planning, biopsy technique, procedure complications and their management. The results of investigation of 81 patients are presented. According to imaging guidance type the patients were subdivided in two main groups - US guided biopsy (26 patients, 26 procedures) and CT guided biopsy (55 patients, 59 procedures). 85 procedures were performed. In 4 cases the repeated biopsy procedure has been performed as the obtained specimen appeared to be non informative. Adequate tissue material was obtained at the first attempt in 77 (95.1 %) cases; in 4 (4.9%) cases the repeated procedure was needed (when the target size was above 2-5 or >5 cm using CT guided biopsy and it was due to tumor necrosis. Procedure related complications were detected in 1 (%) case (CT guided biopsy). In 1 case the significant pain, requiring administration of additional analgetics in postprocedure period was mentioned. Percutaneous US and CT guided bone and soft tissue lesions biopsy is an effective, highly accurate, and safe method of tissue obtaining for the diagnosis of indeterminate lesions. US is fast, cheap, avoids ionizing radiation, and allows the needle tip to be monitored throughout the procedure. CT has the ability to visualize both bone and soft tissue with the advantage of making easier needle localization into lesions too deep to see on US. CT also allows for better visualization lesions with a large amount of overlying cortex, and deep-seated lesions with extensive overlying soft tissue. CT-guided percutaneous biopsy is a safe and accurate method. US is the preferable tool for biopsy procedure guidance if the target is adequately imaged by US. CT should be used in cases when US imaging is not possible due to visualization problem. PMID- 26870972 TI - BASAL CELL CARCINOMA OF THE HEAD-AND-NECK REGION: A SINGLE CENTER ANALYSIS OF 1,750 TUMORS. AB - Basal cell carcinoma (BCC) is the most common malignancy in humans with a pre dominance for the sun-exposed head-and-neck region. Its incidence is rising world wide. Early detection and appropriate treatment ensures an excellent prognosis. We analyzed patients with BCC of the head-and-neck region treated at our Department from January 2008 to December 2012 with a follow-up between 2 to 6 years. Data were collected retrospectively. During a 4-year period, 1,750 BCC lesions of head-and-neck region were excised from 1,380 patients. Distribution of gender among the patients was nearly even. Mean age of patients was 74.3+/-11.4 years. Solid histological subtype dominated the series. Most tumors were removed surgically by delayed MOHS technique (77.0%). The recurrence rate of BCC was 1.6%. The highest recurrence rate of 15.5% was seen in cases of morphea-like BCC compared to 3.9% among solid BCC. The recurrence rate among R0 resected tumors was 0.24% compared to 19.8% among R1-resections (Pearson's Chi-square 56.000). The majority of recurrences occurred within the first 5 year-interval (64%). Multivariate analysis of risk factors for recurrences demonstrated an Odd's ratio for recurrences of 54.89 (95% confidence interval, 21.16, 142.37) in case of R1 resection status. Gender had a minor influence with a slight benefit toward males versus females (Odd's ratio 0.51; 95% confidence interval, 0.28, 0.92). The age of the patients had no impact on recurrence rate. Although there is relatively low mortality attributable to BCC, the morbidity and cost of treatment are significant. Surgical excision remains the mainstay of treatment. For head-and neck BCC, delayed MOHS surgery offers significantly lower recurrence in both primary BCC and recurrent (secondary) BCC. PMID- 26870973 TI - [ADIPONECTIN AND A VIOLATION OF METABOLIC CONTROL AT DIFFERENT STAGES OF NONALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH TYPE 2 DIABETES]. AB - One of the urgent problems of Endocrinology is the study of the mechanisms of formation and progression of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus (DM) type 2. Prognosis depends on the stage of NAFLD in which the changes occur and secretion of adipocytokines in the first place, adiponectin. The aim of the study was to: define adiponectin levels in the circulation of patients with type 2 diabetes at different stages of NAFLD and its impact on the detection of metabolic changes, the establishment of linkages with carbohydrate, lipid, protein metabolism, and liver function. The study determined the relevance of the study of pathogenetic mechanisms of NAFLD in the future, because the violation of metabolic control and reduce the protective properties of adipocytokines in patients with comorbid disorders is of great interest to further improve diagnostic capabilities, prevent complications and improve the quality of life of these patients. PMID- 26870974 TI - [FREQUENCY OF POLYMORPHISM OF VKORC1 AND CYP2C9 GENES IN TWO REGIONS OF GEORGIA]. AB - The aim of the research was to study the frequency of VKROC1 and CYP2C9 genes different alleles for healthy donors and for patients with thrombosis, in two regions of Georgia - in Samegrelo and in Tbilisi and to reveal the interdependence of the studied genes products in the treatment of thrombosis with warfarin. Warfarin is an anticoagulant, causing the inactivation of the VKORC1 gene product, which is one of the clotting factors. The protein product of CYP2C9 gene is involved in the metabolism of warfarin. Genotyping of blood samples for studied genes alleles was carried out using a tube scanner (ESE Quant Tube Scaner), allowing to identify SNPs. In the studied group of patients with thrombosis from Samegrelo region the wild-type homozygotes by the gene VKORC1 were - 90%; heterozygotes - 10%; mutant homozygotes have not met at all. In the studied group of patients with thrombosis from Tbilisi, also predominated homozygous wild type (60%); heterozygotes were - 40%; mutant homozygotes were not met. The genotypes of healthy donors fromTbilisi does not differed from the same indicator of of Samegrelo (homozygous "wild" AA - 37%; genotype AB - 47%; and mutant genotype - BB - 16%). In patients with thrombosis, from Samegrelo, wild tipe homozygotes and heterozygotes by CYP2C9 gene were almost the same rate (51% and 49% -, respectively); mutant homozygotes were not revealed. In patients from Tbilisi, the frequency of wild-type homozygotes was 70%, heterozygotes and mutant homozygotes was 20% and 10% - respectively. The ratio of the frequencies of CYP2C9 gene alleles in healthy donors from Tbilisi and Samegrelo is not different - wild-type homozygotes - 77%; heterozygotes - 23%; mutant homozygotes in both regions were not met. VKORC1 and / or CYP2C9 genes polymorphisms are presented in a number of clinical dosing algorithms and in prospective clinical trials. It is revealed the significant variation of genotypes in patients with thrombosis (in both studied regions), which indicates the importance of as in treatment process, as well as for the prevention of thrombosis. PMID- 26870975 TI - [THE ROLE OF GENETIC POLYMORPHISMS TOLL-LIKE RECEPTOR 4 AND 7 IN THE CHRONIC HEPATITIS C AND GENDER FEATURES OF THEIR DISTRIBUTION]. AB - The aim of the study was to investigate the prevalence of polymorphisms Asp299Gly (rs4986790) TLR4 gene and Gln11Leu (rs179008) TLR7 gene in patients with chronic hepatitis C in general and in gender distribution. To achieve this goal the study using the methods of "case-control", which included 125 patients with chronic hepatitis C who were treated in the Poltava Regional Clinical Hospital of Infectious Diseases. The group of population control for the study of the prevalence of polymorphisms Asp299Gly TLR4 gene included 90 healthy residents of the Poltava region, for Gln11Leu gene TLR7 - 85. Gender groups were equivalent. The study found that in patients with chronic hepatitis C genotype Asp299Gly TLR4 gene was detected in 15.2%, allele 299Gly - in 7.6%, which is 4.5-4.6 times higher than their rate in control group (3.3% and 1.7%, respectively, p<0.01). The presence of polymorphism of the TLR4 gene in the genome can be considered as a predictor of development of chronic hepatitis C, factors of increased risk are the Asp299Gly genotype and the allele 299Gly (OR=5.19, p<0.01 and OR=4.85, p<0.05 respectively). Rolymorphic genotypes Gln11Leu and Leu11Leu of the TLR7 gene recorded in 18.4% of patients with chronic hepatitis C, among them Gln11Leu heterozygous genotype was detected in 16.8%, homozygous Leu11Leu - at 1.6%, with no statistical difference from the population control (25.9%, 22.4%, 3.5%, respectively, p>0.05). "Mutant" genotypes of the TLR7 gene were determined significantly more often in women with chronic hepatitis C (27.1%) and in healthy people (39.5%) comparing to men (13.0% and 14.9%, respectively, p<0.05). PMID- 26870976 TI - [PSYCHOEDUCATIONAL PROGRAM AS A WAY OF CORRECTING MOTIVATIONAL COMPONENTS IN PATIENTS WITH PARANOID SCHIZOPHRENIA WITH ABDOMINAL OBESITY]. AB - The aim of the study was to investigate the influence of motivational and targeted psychoeducational programs designed for patients with paranoid schizophrenia with abdominal obesity. We observed 34 women aged 18-42 with continuous-flow type paranoid schizophrenia. All patients had a concomitant abdominal obesity, which developed secondarily after long-term administration of second generation antipsychotic medications (at least 1 year). Based on clinical psychopathological and psychometric methods of assessment and on the analysis of Treatment Satisfaction Questionnaire we have developed modules for psychoeducational programs. Based on the results of the treatment we conclude that the application of psychoeducational programs is an effective component of complex treatment of patients with paranoid schizophrenia. Abdominal obesity should be regarded as an important and the main side effect of long-term therapy with atypical antipsychotic medications. It has a marked negative effect on subjective assessment of patients and decreases the level of their mental and social adaptation. This factor should be the basis for the formation of re socialization and compliance-oriented actions. PMID- 26870977 TI - THE CURRENT PROBLEMS OF NONSPECIFIC BACK PAIN. AB - The article deals with various aspects of pain in degenerative diseases of the spine and with the actual problems of non-specific back pain. The data on the mechanisms of pain and analgesic treatment algorithms of the patients with radicular syndrome, and pharmacological and non-pharmacological therapies is provided. The effect of structural-modifying drugs in relief of nonspecific back pain was investigated and compared with a traditional nonsteroidal anti inflammatory drug (NSAID) therapy in combination with B vitamins, without chondroprotectors. The study population was composed of 85 patients (42 men and 43 women) aged 38 to 68 years (mean age - (46,3+/-2,6) years) with chronic vertebral pain syndromes (VPS). For objectification assessment of pain, severity of pain, and evaluate the effectiveness of therapy we used the visual analog scale (VAS).The majority (88%) of the patients included in the study, complained of a moderately severe pain (from 40 to 70 mm on the VAS). Patients were divided into two groups. The first (primary) group consisted of 55 patients (30 men and 25 women). The following treatment was applied: all patients of the first group, in addition to the NSAID administered with hondroprotektror arbitrarily - Struktum 1000 mg twice a day or 300 mg Piaskledin once a day for 40-60 days.The second (control) group consisted of 30 patients (14 men, 16 women). Patients in the control group administered with a traditional NSAID therapy in combination with B vitamins, without chondroprotectors. The results of the study on the influence of drugs Piaskledin 300, Struktum for the relief of nonspecific back pain revealed that in the treatment of vertebral pain, a combination of non steroidal anti-inflammatory drugs with structure-modifying agents could achieve rapid rehabilitation of patients with locomotor activity and improve quality of life in general. PMID- 26870978 TI - THE CONTENT OF MICROELEMENTS IN BLOOD SERUM AND ERYTHROCYTES IN CHILDREN WITH DIABETES MELLITUS TYPE I DEPENDING ON LEVEL OF GLYCEMIC CONTROL. AB - The aim of this paper is to investigate the content of chromium, cobalt and nickel in serum and erythrocytes in children with type 1 diabetes mellitus, depending on the level of glycemic control. The study was conducted on 68 children with type 1 diabetes mellitus. The patients were divided into four groups based on glycemic control. Group I was composed of 9 children with optimal level of glycemic control. Group II - 25 children with suboptimal level of glycemic control. Group III - 34 children with a high risk to life level of glycemic control. Group IV (control group) consisted of 30 healthy children. Compensation state of type 1 diabetes was evaluated according to ISPAD (Consensus for the Management of Type 1 Diabetes Mellitus in Children and Adolescens 2000). The content of trace elements in biological agents was determined by atomic absorbtion spectrophotometry method with C-115M1 mass-spectrophotometer, manufactured by "Selmi" enterprise (Ukraine). It is found that there is a decrease in serum concentrations of chromium and erythrocyte content of cobalt in patients with optimal level of glycemic control. The deficiency of chromium is accompanied by the deficiency of cobalt in patients with suboptimal level of glycemic control. The lower levels of cobalt and nickel are recorded simultaneously, but there is theexcess of chromium in the erythrocytes of these patients. Patients, who suffer from 1 type diabetes mellitus and high risk for life level of glycemic control have considerable polideficiency of cobalt, nickel and chromium in serum.The increasing level of chromium was recorded only in the erythrocytes. The level of glycemic control and the duration of 1 type diabetes mellitus are important in the forecasting of the development of chronic diabetic complications. It is found that the duration of 1 type diabetes mellitus influences the levels of cobalt and nickel in serum mostly, while the level of glycemic control influences the chromium content. PMID- 26870979 TI - [CEFTRIAXONE-INDUCED GALLBADDER LITHIASIS IN CASE OF INTENSTINAL BACTERIAL INFECTIONS (CASE REPORTS)]. AB - Ceftriaxone is a third generation cephalosporin antibiotic and is one of the most often applicable parenteral drug, which has wide antimicrobial activity range. According to the literature gall bladder lithiasis is a complication which is described in the first days of the treatment with this antibiotic. The cases are seen mostly as undergdiagnosed conditions when ultrasound examination is performed due to the abdominal colics. The aim of the study was to observe Cholelithiasis in ceftriaxone-treated patients. Last year few cases of Cholelithiasis were observed in Children's Infectious Diseases Hospital. All of them were related to the dysentery treatment with ceftriaxone. All of the cases of Cholelithiasis were diagnosed at the beginning of the antibiotic therapy (in first 2-3 days of hospitalization). Gall bladder concernments/sludge were found accidentally. Cholelithiasis in these cases was transitory and in 2 weeks ultrasound investigation revealed no calculi/sludge in the gall bladder. Further findings are supposed to be analyzed on a bigger number of the patients. It is necessary to follow up with gall bladder concernments till their absolute resolution. PMID- 26870980 TI - [METABOLIC PROCESSES OF ORGANISM IN REMOTE PERIOD AFTER THE COMBINED EFFECTS OF RADIATION AND EMOTIONAL STRESS]. AB - Aim of the research was to study the role of free radical oxidation in the tissues of adrenal and immune organs and cells in remote period after combined effects of sublethal dose of gamma radiation (6 Gy) and emotional stress. Forty male Wistar rats were divided into four groups: I - control; II - exposed to emotional stress; III - exposed to radiation; IV - under the combined effects of emotional stress and radiation. Emotional stress in groups II and IV was simulated by tail suspension. In groups III and IV rats were irradiated once 90 days before the investigation at 6 Gy via TERAGAM So60 ("ISOTREND spol. s.r.o.", Czech Republic). The results of study showed that after the long term exposure gamma radiation has inhibitory effect of the radiation factor in the antioxidant protection. Ionizing radiation combined with emotional stress in remote period has a more pronounced effect on the formation of lipid hyper peroxidation syndrome than separately. Influence of the combined effects of emotional stress and ionizing radiation resulted in increased levels of DC and MDA, inhibition of enzyme activity of catalase and glutathione reductase in almost all the study objects, resulting in the development of dual-oxidative stress. PMID- 26870981 TI - SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY). AB - In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity. PMID- 26870982 TI - [SOME ASPECTS OF URBAN POPULATION AWARENESS ABOUT JOINT RESPONSIBILITY FOR OWN HEALTH]. AB - One of the key goals of public health policy is to improve the joint responsibility of the population in the promotion of their health. In this context, the aim of this study was to determine the public opinion poll on attitudes to own health and to health care. Total covered 450 people, aged 18 to 60 years. The share of women was 60.0%, men - 40.0%. Almost half of respondents (47.0%) had higher education, 36.0% - specialized secondary education and 17.0% - secondary education. More than half (60.0%) of respondents were employed in the production of intellectual work, 40.0% - individuals, over 2/3 (67.2%) of the respondents at the time of the survey had a family. As a result of self-rated health, a third (35.6%) of the respondents rated their health as good to excellent. Men are more often evaluated positively their health than women. Persons engaged in mental labor rarely considered themselves unhealthy than engaged in the production of physical labor. The majority of respondents agree that the health - the most important thing in life (82.9%), for young people it is not significant and is ranked only third place (4.7%), giving primacy of material well-being (73.7%), and the appearance of the human (15.8%). They also found that the higher the education level, the more demanding patients to themselves as responsible for the health and the quality of medical services provided by the clinic. The bulk of the population doesn't want to part with the usual attributes inherent in the current system of public health (69.6%) state and free. With the introduction of compulsory health insurance of the population is afraid of losing with the innovations at least minimal social guarantees for the protection of health. PMID- 26870983 TI - [THE LEVEL OF NAPHTHALENE AND ITS DERIVATES IN TOBACCO SMOKE]. AB - The composition of cigarette smoke in spite of its tremendous complexity is relatively known, but little is known about the influence of Ecologic Factors (air flows, temperature, light) on the Migration Character of individual and specific components of Tobacco Smoke constansate in environmental atmosphere on different distance from burning cigarette. Oxidation in air, and photochemical reactions can produce many compounds which were not originally present in the Tobacco Smoke. Gas liquid Chromatography with high-resolution capillary column is applied. The tobacco skome volume was taked and analyzed in the distance of 2,0 m and 4,0 m from burning cigarette. The content of naphthalene and its derivates in the air samples was revealed. Our data show that distance of exposition from burning cigarette can change the structure and volume of each component of tobacco smoke. The studies are necessary in different direction. First, this phenomen still needs to be explained. The second, it would be interesting to investigate the retention of tobacco smoke components in lung tissue, for a considerable time after the smoking process. The obtained data is very important from the point of ecological assessment of the environment and sensitivity to the components of tobacco smoke. PMID- 26870984 TI - ALTERATION OF OXIDATIVE METABOLISM AND IMMUNOLOGICAL PARAMETERS UNDER THE INFLUENCE OF UVA RADIATION IN WOMEN OF DIFFERENT AGES. AB - Purpose of study was to investigate the alteration of oxidative and immunological metabolism in blood of reproductive and menopausal age women after UVA irradiation. Women of two groups (1 - menopausal, 2 - reproductive age) were exposed to radiation with wave length 320-400 nm for 5-10 minutes per session in the solarium for the period of 3 months (6 days per month).. Parameters of oxidative metabolism - activity of red blood cells (RBC), antioxidant enzymes catalase (CAT) and superoxiddismutase (SOD) were studied by spectrophotometric method; reactive oxygen (O2-) and lipid (LOO/) free radicals content in whole blood were studied by Electron Paramagnetic Resonance (EPR) methods with use of specific spin-traps - 5,5-Dimethyl-1-Pyrroline-N-Oxide (DMPO) and alpha-phenyl-N tert-butylnitrone (PBN) (SIGMA). Parameters of immunological metabolism - IFN alpha, IL-2, IL-10 cytokines content in blood were studied by immunoenzymatic assay ELISA. The study protocol has been approved by the Ethical Committee of the Tbilisi State Medical University. After the course of UVA irradiation in menopausal women CAT activity increased by 20%, SOD - by 24%, and EPR signal of spin trapped lipoperoxide radicals was detected. No alterations in blood redox balance were detected in women of reproductive age. Values of blood immunological parameters in menopausal women were not changed under the influence of UV radiation; in women of reproductive age IL-10 content increase by 93% (within a normal value range) was revealed. Research results have shown that UVA rays cause a particularly significant influence on the oxidative metabolism in the women of menopausal age. Increase of IL-10 blood levels in women of reproductive age (considering its imunosupressing activity) represents an additional risk of cancerogenesis. Based on the study results, we recommend avoiding UV (including UVA) radiation procedures to women of both reproductive and menopausal ages. PMID- 26870985 TI - Associations Between Dehydration, Cognitive Impairment, and Frailty in Older Hospitalized Patients: An Exploratory Study. AB - HOW TO OBTAIN CONTACT HOURS BY READING THIS ARTICLE INSTRUCTIONS 1.2 contact hours will be awarded by Villanova University College of Nursing upon successful completion of this activity. A contact hour is a unit of measurement that denotes 60 minutes of an organized learning activity. This is a learner-based activity. Villanova University College of Nursing does not require submission of your answers to the quiz. A contact hour certificate will be awarded once you register, pay the registration fee, and complete the evaluation form online at http://goo.gl/gMfXaf. To obtain contact hours you must: 1. Read the article, "Associations Between Dehydration, Cognitive Impairment, and Frailty in Older Hospitalized Patients: An Exploratory Study" found on pages 19-27, carefully noting any tables and other illustrative materials that are included to enhance your knowledge and understanding of the content. Be sure to keep track of the amount of time (number of minutes) you spend reading the article and completing the quiz. 2. Read and answer each question on the quiz. After completing all of the questions, compare your answers to those provided within this issue. If you have incorrect answers, return to the article for further study. 3. Go to the Villanova website listed above to register for contact hour credit. You will be asked to provide your name; contact information; and a VISA, MasterCard, or Discover card number for payment of the $20.00 fee. Once you complete the online evaluation, a certificate will be automatically generated. This activity is valid for continuing education credit until April 30, 2019. CONTACT HOURS This activity is co-provided by Villanova University College of Nursing and SLACK Incorporated. Villanova University College of Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. ACTIVITY OBJECTIVES 1. Describe the incidence of dehydration in older hospitalized patients. 2. Identify risk and management strategies related to dehydration in older hospitalized patients. DISCLOSURE STATEMENT Neither the planners nor the author have any conflicts of interest to disclose. The current exploratory study (a) assessed the prevalence of dehydration in older adults (age <=60 years) with and without cognitive impairment (CI) admitted to the hospital; and (b) examined associations between dehydration, CI, and frailty. Forty-four patients participated and dehydration was assessed within 24 hours of admission and at Day 4 or discharge (whichever occurred first). Patients' cognitive function and frailty statuses were assessed using validated instruments. Twenty seven (61%) patients had CI and 61% were frail. Prevalence of dehydration at admission was 29% (n = 12) and 19% (n = 6) at study exit, and dehydration status did not differ according to CI or frailty status. However, within the non-CI group, significantly more frail than fit patients were dehydrated at admission (p = 0.03). Findings indicate dehydration is common among older hospitalized patients and that frailty may increase the risk for dehydration in cognitively intact older adults. [Journal of Gerontological Nursing, 42(5), 19-27.]. PMID- 26870986 TI - Memory Matters: A Mixed-Methods Feasibility Study of a Mobile Aid to Stimulate Reminiscence in Individuals With Memory Loss. AB - Reminiscence interventions are potentially effective in improving well-being of persons with memory loss (PWMLs) and may also enhance relationships with family and professional caregivers. Using a parallel convergent mixed-methods design, the feasibility of "Memory Matters" (MM), a mobile device application developed to promote reminiscence, was evaluated. Eighteen PWMLs and eight family members were enrolled from a long-term care facility and asked to use MM for 4 weeks. Participants were observed using MM at enrollment and 2 weeks and completed 1 month interviews. Six staff participants also completed a system review checklist and/or focus group at 1 month. Three qualitative domains were identified: (a) context of use, (b) barriers to use, and (c) MM influences on outcomes. Participants reported real-time social engagement, ease of use, and other benefits. However, PWMLs were unlikely to overcome barriers without assistance. Empirical data indicated that family and staff perceived MM favorably. Participants agreed that MM could provide stimulating, reminiscence-based activity. [Journal of Gerontological Nursing, 42(7), 15-24.]. PMID- 26870987 TI - "It Doesn't Require Much Effort Once You Get to Know Them": Certified Nursing Assistants' Views of Communication in Long-Term Care. AB - Certified nursing assistants (CNAs) provide the majority of hands-on care and become highly sensitive to residents' communication behaviors. Yet, CNAs feel disempowered when communicating residents' concerns to higher levels of authority. A grounded theory approach using focus group interviews with 23 CNAs was used to describe the communication environment in long-term care (LTC) and explore CNAs' perceptions of the acceptability of communication plans, a recent Canadian intervention to facilitate resident-staff communication. Findings suggest the communication environment in LTC relates to three overlapping constructs: (a) CNA and resident communication style; (b) paradox of context; and (c) dedication to residents. Although CNAs frequently interact with residents, a division between "top and bottom staff" communication was apparent in the findings. The current study suggested that communication plans may improve the communication environment in LTC settings. [Journal of Gerontological Nursing, 42(4), 42-51.]. PMID- 26870988 TI - Current Telerehabilitation Research With Older Adults at Home: An Integrative Review. AB - Increased demand for in-home rehabilitation services for older adults may be met through telerehabilitation information and communication technologies. The current article reports the results of an integrative literature review summarizing current in-home telerehabilitation research with older adults. Nine studies from 2006-2015 are included. Six studies employed a remote therapist using real-time video. Three studies used text- or web-based messaging and electronic surveys. Six studies relied on dial-up Internet service and the remaining three studies used broad-band Internet connections. Future research should address (a) in-home and wearable sensing technologies to monitor health and (b) mobile devices, such as tablet computers, to collect patient self reports. Interoperable platforms are needed to integrate disparate devices and support continuity of care across post-acute care settings. [Journal of Gerontological Nursing, 42(10), 15-20.]. PMID- 26870989 TI - Orbital dependent ultrafast charge transfer dynamics of ferrocenyl-functionalized SAMs on gold studied by core-hole clock spectroscopy. AB - Understanding the charge transport properties in general of different molecular components in a self-assembled monolayer (SAM) is of importance for the rational design of SAM molecular structures for molecular electronics. In this study, we study an important aspect of the charge transport properties, i.e. the charge transfer (CT) dynamics between the active molecular component (in this case, the ferrocenyl moieties of a ferrocenyl-n-alkanethiol SAM) and the electrode using synchrotron-based core-hole clock (CHC) spectroscopy. The characteristic CT times are found to depend strongly on the character of the ferrocenyl-derived molecular orbitals (MOs) which mediate the CT process. Furthermore, by systemically shifting the position of the ferrocenyl moiety in the SAM, it is found that the CT characteristics of the ferrocenyl MOs display distinct dependence on its distance to the electrode. These results demonstrate experimentally that the efficiency and rate of charge transport through the molecular backbone can be modulated by resonant injection of charge carriers into specific MOs. PMID- 26870990 TI - 3D periodic multiscale TiO2 architecture: a platform decorated with graphene quantum dots for enhanced photoelectrochemical water splitting. AB - Micropatterned TiO2 nanorods (TiO2NRs) via three-dimensional (3D) geometry engineering in both microscale and nanoscale decorated with graphene quantum dots (GQDs) have been demonstrated successfully. First, micropillar (MP) and microcave (MC) arrays of anatase TiO2 films are obtained through the sol-gel based thermal nanoimprinting method. Then they are employed as seed layers in hydrothermal growth to fabricate the 3D micropillar/microcave arrays of rutile TiO2NRs (NR), which show much-improved photoelectrochemical water-splitting performance than the TiO2NRs grown on flat seed layer. The zero-dimensional GQDs are sequentially deposited onto the surfaces of the microscale patterned nanorods. Owing to the fast charge separation that resulted from the favorable band alignment of the GQDs and rutile TiO2, the MP-NR-GQDs electrode achieves a photocurrent density up to 2.92 mA cm(-2) under simulated one-sun illumination. The incident-photon-to current-conversion efficiency (IPCE) value up to 72% at 370 nm was achieved on the MP-NR-GQDs electrode, which outperforms the flat-NR counterpart by 69%. The IPCE results also imply that the improved photocurrent mainly benefits from the distinctly enhanced ultraviolet response. The work provides a cost-effective and flexible pathway to develop periodic 3D micropatterned photoelectrodes and is promising for the future deployment of high performance optoelectronic devices. PMID- 26870992 TI - Mutual amplification of HNF4alpha and IL-1R1 composes an inflammatory circuit in Helicobacter pylori associated gastric carcinogenesis. AB - Helicobacter pylori (Hp) is an environmental inducer of gastritis and gastric cancer (GC). The immune response to Hp and the associated changes in somatic gene expression are key determinants governing the transition from gastritis to GC. We show that hepatocyte nuclear factor 4alpha (HNF4alpha) is upregulated by Hp infection via NF-kappaB signaling and that its protein and mRNA levels are elevated in GC. HNF4alpha in turn stimulates expression of interleukin-1 receptor 1(IL-1R1), which amplifies the inflammatory response evoked by its ligand IL 1beta. IL-1beta/IL-1R1 activates NF-kappaB signaling, thereby increasing HNF4alpha expression and forming a feedback loop that sustains activation of the NF-kappaB pathway and drives the inflammation towards GC. Examination of clinical samples revealed that HNF4alpha and IL-1R1 levels increase with increasing severity of Hp-induced gastritis and reach their highest levels in GC. Co expression of HNF4alpha and IL-1R1 was a crucial indicator of malignant transformation from gastritis to GC, and was associated with a poorer prognosis in GC patients. Disruption of the HNF4alpha/IL-1R1/IL-1beta/NF-kappaB circuit during Hp infection maybe an effective means of preventing the associated GC. PMID- 26870991 TI - Histone acetyltransferase inhibitor CPTH6 preferentially targets lung cancer stem like cells. AB - Cancer stem cells (CSCs) play an important role in tumor initiation, progression, therapeutic failure and tumor relapse. In this study, we evaluated the efficacy of the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2 yl]hydrazone (CPTH6), a novel pCAF and Gcn5 histone acetyltransferase inhibitor, as a small molecule that preferentially targets lung cancer stem-like cells (LCSCs) derived from non-small cell lung cancer (NSCLC) patients. Notably, although CPTH6 inhibits the growth of both LCSC and NSCLC cell lines, LCSCs exhibit greater growth inhibition than established NSCLC cells. Growth inhibitory effect of CPTH6 in LCSC lines is primarily due to apoptosis induction. Of note, differentiated progeny of LCSC lines is more resistant to CPTH6 in terms of loss of cell viability and reduction of protein acetylation, when compared to their undifferentiated counterparts. Interestingly, in LCSC lines CPTH6 treatment is also associated with a reduction of stemness markers. By using different HAT inhibitors we provide clear evidence that inhibition of HAT confers a strong preferential inhibitory effect on cell viability of undifferentiated LCSC lines when compared to their differentiated progeny. In vivo, CPTH6 is able to inhibit the growth of LCSC-derived xenografts and to reduce cancer stem cell content in treated tumors, as evidenced by marked reduction of tumor-initiating capacity in limiting dilution assays. Strikingly, the ability of CPTH6 to inhibit tubulin acetylation is also confirmed in vivo. Overall, our studies propose histone acetyltransferase inhibition as an attractive target for cancer therapy of NSCLC. PMID- 26870993 TI - Cancer-selective cytotoxic Ca2+ overload in acute myeloid leukemia cells and attenuation of disease progression in mice by synergistically acting polyphenols curcumin and carnosic acid. AB - Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by extremely heterogeneous molecular and biologic abnormalities that hamper the development of effective targeted treatment modalities. While AML cells are highly sensitive to cytotoxic Ca2+ overload, the feasibility of Ca2+- targeted therapy of this disease remains unclear. Here, we show that apoptotic response of AML cells to the synergistically acting polyphenols curcumin (CUR) and carnosic acid (CA), combined at low, non-cytotoxic doses of each compound was mediated solely by disruption of cellular Ca2+ homeostasis. Specifically, activation of caspase cascade in CUR+CA-treated AML cells resulted from sustained elevation of cytosolic Ca2+ (Ca2+cyt) and was not preceded by endoplasmic reticulum stress or mitochondrial damage. The CUR+CA-induced Ca2+cyt rise did not involve excessive influx of extracellular Ca2+ but, rather, occurred due to massive Ca2+ release from intracellular stores concomitant with inhibition of Ca2+cyt extrusion through the plasma membrane. Notably, the CUR+CA combination did not alter Ca2+ homeostasis and viability in non-neoplastic hematopoietic cells, suggesting its cancer-selective action. Most importantly, co administration of CUR and CA to AML-bearing mice markedly attenuated disease progression in two animal models. Collectively, our results provide the mechanistic and translational basis for further characterization of this combination as a prototype of novel Ca2+-targeted pharmacological tools for the treatment of AML. PMID- 26870994 TI - Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry. AB - Influenza viruses possess a great threat to human health, but there is still no effective drug to deal with the outbreak of possible new influenza subtypes. In this study, we first fractionated sialylated immunoglobulin G (IgG), mainly Fab sialylated fraction, with sambucus nigra agglutinin affinity chromatography. We then demonstrated that sialylated IgG possessed more effective neutralizing activity against 2009 A (H1N1) subtype than that of IgG mixture, and sialosides on the Fab is crucial in this neutralization reaction as when such residues were removed with neuraminidase A digestion the blocking effect was significantly reduced. It appears that sialic acid residues attached to Fab could serve as binding moieties to receptor binding site of influenza virus. These findings indicate that sialylated IgG probably is an effective anti-influenza broad spectrum drug utilizing its receptor mimicry to competitively inhibit the attachment of influenza viruses with sialic acid receptors on target cells. This property would be particularly useful if it can be applied to prevent newly emerged influenza virus strain infections in future epidemics. PMID- 26870995 TI - EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer. AB - The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan(r) Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization. PMID- 26870996 TI - Survival benefit of surgery with radiotherapy vs surgery alone to patients with T2-3N0M0 stage esophageal adenocarcinoma. AB - BACKGROUND & AIMS: This study is designed to analyze survival benefit of (neo-) adjuvant radiotherapy to patients with T2-3N0M0 stage esophageal adenocarcinoma (EAC). METHODS: T2-3N0M0 stage EAC patients from 2004 to 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, sex, race were summarized. Univariate, multivariate analysis, and stratified cox analysis based on different T stages were performed to explore the survival effect of (neo-)adjuvant radiotherapy to T2-3N0M0 stage EAC. RESULTS: T2 3N0M0 stage EAC patients with surgery were more likely to be white race, T3 stage. Univariate analysis showed sex, age, and T stage were the prognostic factors of survival (P<0.05). Multivariate analysis proved (neo-)adjuvant radiotherapy can prolong survival time of T2-3N0M0 stage EAC (P<0.05). Further analysis based on different T stages showed that both neoadjuvant radiotherapy (HR 0.615; 95% CI 0.475-0.797) and adjuvant radiotherapy (HR 0.597; 95% 0.387 0.921) significantly reduced the risk of death of T3N0M0 stage EAC, but neither of which significantly reduced death risk of T2N0M0 stage EAC (P>0.05). CONCLUSIONS: sex, age are the independent prognostic factors of T2-3N0M0 EAC. Significant survival benefit of (neo-)adjuvant radiotherapy is only observed in patients with T3N0M0 stage EAC, but not in those with T2N0M0 stage. PMID- 26870997 TI - The status of epidermal growth factor receptor in borderline ovarian tumours. AB - The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18 21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs. PMID- 26870999 TI - Gypenoside L, Isolated from Gynostemma pentaphyllum, Induces Cytoplasmic Vacuolation Death in Hepatocellular Carcinoma Cells through Reactive-Oxygen Species-Mediated Unfolded Protein Response. AB - Exploring novel anticancer agents that can trigger non-apoptotic or non autophagic cell death is urgent for cancer treatment. In this study, we screened and identified an unexplored anticancer activity of gypenoside L (Gyp-L) isolated from Gynostemma pentaphyllum. We showed that treatment with Gyp-L induces non apoptotic and non-autophagic cytoplasmic vacuolation death in human hepatocellular carcinoma (HCC) cells. Mechanically, Gyp-L initially increased the intracellular reactive oxygen species (ROS) levels, which, in turn, triggered protein ubiquitination and unfolded protein response (UPR), resulting in Ca(2+) release from endoplasm reticulum (ER) inositol trisphosphate receptor (IP3R) operated stores and finally cytoplasmic vacuolation and cell death. Interruption of the ROS-ER-Ca(2+) signaling pathway by chemical inhibitors significantly prevented Gyp-L-induced vacuole formation and cell death. In addition, Gyp-L induced ER stress and vacuolation death required new protein synthesis. Overall, our works provide strong evidence for the anti-HCC activity of Gyp-L and suggest a novel therapeutic option by Gyp-L through the induction of a unconventional ROS ER-Ca(2+)-mediated cytoplasmic vacuolation death in human HCC. PMID- 26870998 TI - Integrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer. AB - BACKGROUND: Studies on the accuracy of microRNAs (miRNAs) in diagnosing non-small cell lung cancer (NSCLC) have still controversial. Therefore, we conduct to systematically identify miRNAs related to NSCLC, and their target genes expression changes using microarray data sets. METHODS: We screened out five miRNAs and six genes microarray data sets that contained miRNAs and genes expression in NSCLC from Gene Expression Omnibus. RESULTS: Our analysis results indicated that fourteen miRNAs were significantly dysregulated in NSCLC. Five of them were up-regulated (miR-9, miR-708, miR-296-3p, miR-892b, miR-140-5P) while nine were down-regulated (miR-584, miR-218, miR-30b, miR-522, miR486-5P, miR-34c 3p, miR-34b, miR-516b, miR-592). The integrating diagnosis sensitivity (SE) and specificity (SP) were 82.6% and 89.9%, respectively. We also found that 4 target genes (p < 0.05, fold change > 2.0) were significant correlation with the 14 discovered miRNAs, and the classifiers we built from one training set predicted the validation set with higher accuracy (SE = 0.987, SP = 0.824). CONCLUSIONS: Our results demonstrate that integrating miRNAs and target genes are valuable for identifying promising biomarkers, and provided a new insight on underlying mechanism of NSCLC. Further, our well-designed validation studies surely warrant the investigation of the role of target genes related to these 14 miRNAs in the prediction and development of NSCLC. PMID- 26871000 TI - Molecular Dynamics Study on the Inhibition Mechanisms of Drugs CQ1-3 for Alzheimer Amyloid-beta40 Aggregation Induced by Cu(2.). AB - The aggregation of amyloid-beta (Abeta) peptide induced by Cu(2+) is a key factor in development of Alzheimer's disease (AD), and metal ion chelation therapy enables treatment of AD. Three CQi (i = 1, 2, and 3 with R = H, Cl, and NO2, respectively) drugs had been verified experimentally to be much stronger inhibitors than the pioneer clioquinol (CQ) in both disaggregation of Abeta40 aggregate and reduction of toxicity induced by Cu(2+) binding at low pH. Due to the multiple morphologies of Cu(2+)-Abeta40 complexes produced at different pH states, we performed a series of molecular dynamics simulations to explain the structural changes and morphology characteristics as well as intrinsic disaggregation mechanisms of three Cu(2+)-Abeta40 models in the presence of any of the three CQi drugs at both low and high pH states. Three inhibition mechanisms for CQi were proposed as "insertion", "semi-insertion", and "surface" mechanisms, based on the morphologies of CQi-model x (CQi-x, x = 1, 2, and 3) and the strengths of binding between CQi and the corresponding model x. The insertion mechanism was characterized by the morphology with binding strength of more than 100 kJ/mol and by CQi being inserted or embedded into the hydrophobic cavity of model x. In those CQi-x morphologies with lower binding strength, CQi only attaches on the surface or inserts partly into Abeta peptide. Given the evidence that the binding strength is correlated positively with the effectiveness of drug to inhibit Abeta aggregation and thus to reduce toxicity, the data of binding strength presented here can provide a reference for one to screen drugs. From the point of view of binding strength, CQ2 is the best drug. Because of the special role of Asp23 in both Abeta aggregation and stabilizing the Abeta fibril, the generation of a H-bond between CQ3 and Asp23 of the Abeta40 peptide is believed to be responsible for CQ3 having the strongest disaggregation capacity. Therefore, besides strong binding, stronger propensity to H-bond with Asp23 would be another key factor to be taken seriously into account in drug screens. Meanwhile, the structural characteristics of drug CQi itself are also worthy of attention. First, the increasing polarity from CQ1 and CQ2 to CQ3 in turn results in increasing probability and strength of the interaction between the drug and the N-terminal (NT) region of Abeta40, which obviously inhibits Abeta peptide aggregation induced by Cu(2+) binding. Second, both the benzothiazole ring and phenol ring of CQi can overcome the activation energy barrier (~16 kJ/mol) to rotate flexibly around the intramolecular C7-N14 bond to achieve the maximum match and interaction with the ambient Abeta40 residues. Such a structural feature of CQi paves the new way for ones in selection and modification of a drug. PMID- 26871001 TI - Surface Charge Visualization at Viable Living Cells. AB - Scanning ion conductance microscopy (SICM) is demonstrated to be a powerful technique for quantitative nanoscale surface charge mapping of living cells. Utilizing a bias modulated (BM) scheme, in which the potential between a quasi reference counter electrode (QRCE) in an electrolyte-filled nanopipette and a QRCE in bulk solution is modulated, it is shown that both the cell topography and the surface charge present at cellular interfaces can be measured simultaneously at high spatial resolution with dynamic potential measurements. Surface charge is elucidated by probing the properties of the diffuse double layer (DDL) at the cellular interface, and the technique is sensitive at both low-ionic strength and under typical physiological (high-ionic strength) conditions. The combination of experiments that incorporate pixel-level self-referencing (calibration) with a robust theoretical model allows for the analysis of local surface charge variations across cellular interfaces, as demonstrated on two important living systems. First, charge mapping at Zea mays root hairs shows that there is a high negative surface charge at the tip of the cell. Second, it is shown that there are distinct surface charge distributions across the surface of human adipocyte cells, whose role is the storage and regulation of lipids in mammalian systems. These are new features, not previously recognized, and their implications for the functioning of these cells are highlighted. PMID- 26871002 TI - Material Stock Demographics: Cars in Great Britain. AB - Recent literature on material flow analysis has been focused on quantitative characterization of past material flows. Fewer analyses exist on past and prospective quantification of stocks of materials in-use. Some of these analyses explore the composition of products' stocks, but a focus on the characterization of material stocks and its relation with service delivery is often neglected. We propose the use of the methods of human demography to characterize material stocks, defined herein as stock demographics, exploring the insights that this approach could provide for the sustainable management of materials. We exemplify an application of stock demographics by characterizing the composition and service delivery of iron, steel, and aluminum stocks of cars in Great Britain, 2002-2012. The results show that in this period the stock has become heavier, it is traveling less, and it is idle for more time. The visualization of material stocks' dynamics demonstrates the pace of product replacement as a function of its usefulness and enables the formulation of policy interventions and the exploration of future trends. PMID- 26871003 TI - Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity. AB - The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs. PMID- 26871004 TI - In Situ Characterization of Ultrathin Films by Scanning Electrochemical Impedance Microscopy. AB - Control over the properties of ultrathin films plays a crucial role in many fields of science and technology. Although nondestructive optical and electrical methods have multiple advantages for local surface characterization, their applicability is very limited if the surface is in contact with an electrolyte solution. Local electrochemical methods, e.g., scanning electrochemical microscopy (SECM), cannot be used as a robust alternative yet because their methodological aspects are not sufficiently developed with respect to these systems. The recently proposed scanning electrochemical impedance microscopy (SEIM) can efficiently elucidate many key properties of the solid/liquid interface such as charge transfer resistance or interfacial capacitance. However, many fundamental aspects related to SEIM application still remain unclear. In this work, a methodology for the interpretation of SEIM data of "charge blocking systems" has been elaborated with the help of finite element simulations in combination with experimental results. As a proof of concept, the local film thickness has been visualized using model systems at various tip-to-sample separations. Namely, anodized aluminum oxide (Al2O3, 2-20 nm) and self-assembled monolayers based on 11-mercapto-1-undecanol and 16-mercapto-1-hexadecanethiol (2.1 and 2.9 nm, respectively) were used as model systems. PMID- 26871007 TI - Self-averaging and ergodicity of subdiffusion in quenched random media. AB - We study the self-averaging properties and ergodicity of the mean square displacement m(t) of particles diffusing in d dimensional quenched random environments which give rise to subdiffusive average motion. These properties are investigated in terms of the sample to sample fluctuations as measured by the variance of m(t). We find that m(t) is not self-averaging for d<2 due to the inefficient disorder sampling by random motion in a single realization. For d>=2 in contrast, the efficient sampling of heterogeneity by the space random walk renders m(t) self-averaging and thus ergodic. This is remarkable because the average particle motion in d>2 obeys a CTRW, which by itself displays weak ergodicity breaking. This paradox is resolved by the observation that the CTRW as an average model does not reflect the disorder sampling by random motion in a single medium realization. PMID- 26871008 TI - Control and generation of drifting patterns by asymmetrical Fourier filtering. AB - We report the theoretical and experimental demonstration of one-dimensional drifting patterns generated by asymmetrical Fourier filtering in the transverse plane of an optical feedback system with a Kerr type nonlinearity. We show, with good agreement between our theoretical (analytics and numerics) calculations and experimental observations that at the primary instability threshold the group velocity is always different from zero. Consequently, the system is convective at this threshold, then exhibits drifting patterns. PMID- 26871009 TI - Equilibrium microphase separation in the two-leaflet model of lipid membranes. AB - Because of the coupling between local lipid composition and the thickness of the membrane, microphase separation in two-component lipid membranes can take place; such effects may underlie the formation of equilibrium nanoscale rafts. Using a kinetic description, this phenomenon is analytically and numerically investigated. The phase diagram is constructed through the stability analysis for linearized kinetic equations, and conditions for microphase separation are discussed. Simulations of the full kinetic model reveal the development of equilibrium membrane nanostructures with various morphologies from the initial uniform state. PMID- 26871010 TI - Periodically driven DNA: Theory and simulation. AB - We propose a generic model of driven DNA under the influence of an oscillatory force of amplitude F and frequency nu and show the existence of a dynamical transition for a chain of finite length. We find that the area of the hysteresis loop, A_{loop}, scales with the same exponents as observed in a recent study based on a much more detailed model. However, towards the true thermodynamic limit, the high-frequency scaling regime extends to lower frequencies for larger chain length L and the system has only one scaling (A_{loop}~nu^{-1}F^{2}). Expansion of an analytical expression for A_{loop} obtained for the model system in the low-force regime revealed that there is a new scaling exponent associated with force (A_{loop}~nu^{-1}F^{2.5}), which has been validated by high-precision numerical calculation. By a combination of analytical and numerical arguments, we also deduce that for large but finite L, the exponents are robust and independent of temperature and friction coefficient. PMID- 26871011 TI - Large deformation of self-oscillating polymer gel. AB - A self-oscillating gel is a system that generates an autonomous volume oscillation. This oscillation is powered by the chemical energy of the Belousov Zhabotinsky (BZ) reaction, which demonstrates metal ion redox oscillation. A self oscillating gel is composed of Poly-N-isopropylacrylamide (PNIPAAm) with a metal ion. In this study, we found that the displacement of the volume oscillation in a self-oscillating gel could be controlled by its being subjected to a prestraining process. We also revealed the driving mechanism of the self-oscillating gel from the point of view of thermodynamics. We observed that the polymer-solvent interaction parameter chi is altered by the redox changes to the metal ion incorporated in the self-oscillating gel. The prestraining process leads to changes in chi and changes in enthalpy and entropy when the self-oscillating gel is in a reduced and oxidized state. We found that nonprestrained gel samples oscillate in a poor solution (chi>0.5) and prestrained gel samples oscillate in a good solution (chi<0.5). PMID- 26871012 TI - Microscopic treatment of solute trapping and drag. AB - The long wavelength limit of a recent microscopic phase-field crystal (PFC) theory of a binary alloy mixture is used to derive an analytical approximation for the segregation coefficient as a function of the interface velocity, and relate it to the two-point correlation function of the liquid and the thermodynamic properties of solid and liquid phases. Our results offer the first analytical derivation of solute segregation from a microscopic model, and support recent molecular dynamics and numerical PFC simulations. Our results also provide an independent framework, motivated from classical density functional theory, from which to elucidate the fundamental nature of solute drag, which is still highly contested in the literature. PMID- 26871013 TI - Extreme stiffness tunability through the excitation of nonlinear defect modes. AB - The incremental stiffness characterizes the variation of a material's force response to a small deformation change. In lattices with noninteracting vibrational modes, the excitation of localized states does not have any effect on material properties, such as the incremental stiffness. We report that, in nonlinear lattices, driving a defect mode introduces changes in the static force displacement relation of the material. By varying the defect excitation frequency and amplitude, the incremental stiffness can be tuned continuously to arbitrarily large positive or negative values. Furthermore, the defect excitation parameters also determine the displacement region at which the force-displacement relation is being tuned. We demonstrate this phenomenon experimentally in a compressed array of spheres tuning its incremental stiffness from a finite positive value to zero and continuously down to negative infinity. PMID- 26871014 TI - Nonlinear plastic modes in disordered solids. AB - We propose a theoretical framework within which a robust micromechanical definition of precursors to plastic instabilities, often termed soft spots, naturally emerges. They are shown to be collective displacements (modes) z[over ] that correspond to local minima of a barrier function b(z[over ]), which depends solely on inherent structure information. We demonstrate how some heuristic searches for local minima of b(z[over ]) can a priori detect the locus and geometry of imminent plastic instabilities with remarkable accuracy, at strains as large as gamma_{c}-gamma~10^{-2} away from the instability strain gamma_{c}. Our findings suggest that the a priori detection of the entire field of soft spots can be effectively carried out by a systematic investigation of the landscape of b(z[over ]). PMID- 26871015 TI - Sub-Gaussian behavior of the Townsend-Perry constants in turbulent boundary layers. AB - A theory is developed to explain the sub-Gaussian behavior of the Townsend-Perry constants (A_{p}) recently measured for high-order fluctuation moments in turbulent boundary layers. It yields the generalized logarithmic law for high order moments and A_{p}/A_{1}=(l^{*})^{zeta_{p}/p-zeta_{1}}C_{p}^{1/p}/C_{1}, where zeta_{p} are the Kolmogorov-Obukhov-She-Leveque scaling characterizing intermittence effects; l^{*}=1/225 is the only free parameter describing a specific ratio between inertial and energy-containing eddy sizes; C_{p} are raw moments of a Gaussian with unity mean and variance. The predicted A_{p}/A_{1} are in good agreement with experimental data. PMID- 26871016 TI - Anomalous dissipation and kinetic-energy distribution in pipes at very high Reynolds numbers. AB - A symmetry-based theory is developed for the description of (streamwise) kinetic energy K in turbulent pipes at extremely high Reynolds numbers (Re's). The theory assumes a mesolayer with continual deformation of wall-attached eddies which introduce an anomalous dissipation, breaking the exact balance between production and dissipation. An outer peak of K is predicted above a critical Re of 10^{4}, in good agreement with experimental data. The theory offers an alternative explanation for the recently discovered logarithmic distribution of K. The concept of anomalous dissipation is further supported by a significant modification of the k-omega equation, yielding an accurate prediction of the entire K profile. PMID- 26871017 TI - From measurements to inferences of physical quantities in numerical simulations. AB - We propose a change of style for numerical estimations of physical quantities from measurements to inferences. We estimate the most probable quantities for all the parameter region simultaneously by using the raw data cooperatively. Estimations with higher precisions are made possible. We can obtain a physical quantity as a continuous function, which is processed to obtain another quantity. We applied the method to the Heisenberg spin-glass model in three dimensions. A dynamic correlation-length scaling analysis suggests that the spin-glass and the chiral-glass transitions occur at the same temperature with a common exponent nu. The value is consistent with the experimental results. We explained a spin chirality separation problem by a size-crossover effect. PMID- 26871018 TI - Nonequilibrium behaviors of the three-dimensional Heisenberg model in the Swendsen-Wang algorithm. AB - Recently, it was shown [Y. Nonomura, J. Phys. Soc. Jpn. 83, 113001 (2014)JUPSAU0031-901510.7566/JPSJ.83.113001] that the nonequilibrium critical relaxation of the two-dimensional (2D) Ising model from a perfectly ordered state in the Wolff algorithm is described by stretched-exponential decay, and a universal scaling scheme was found to connect nonequilibrium and equilibrium behaviors. In the present study we extend these findings to vector spin models, and the 3D Heisenberg model could be a typical example. To evaluate the critical temperature and critical exponents precisely using the above scaling scheme, we calculate nonequilibrium ordering from the perfectly disordered state in the Swendsen-Wang algorithm, and we find that the critical ordering process is described by stretched-exponential growth with a comparable exponent to that of the 3D XY model. The critical exponents evaluated in the present study are consistent with those in previous studies. PMID- 26871019 TI - Exploring percolative landscapes: Infinite cascades of geometric phase transitions. AB - The evolution of many kinetic processes in 1+1 (space-time) dimensions results in 2D directed percolative landscapes. The active phases of these models possess numerous hidden geometric orders characterized by various types of large-scale and/or coarse-grained percolative backbones that we define. For the patterns originated in the classical directed percolation (DP) and contact process we show from the Monte Carlo simulation data that these percolative backbones emerge at specific critical points as a result of continuous phase transitions. These geometric transitions belong to the DP universality class and their nonlocal order parameters are the capacities of corresponding backbones. The multitude of conceivable percolative backbones implies the existence of infinite cascades of such geometric transitions in the kinetic processes considered. We present simple arguments to support the conjecture that such cascades of transitions are a generic feature of percolation as well as of many other transitions with nonlocal order parameters. PMID- 26871020 TI - Simple average expression for shear-stress relaxation modulus. AB - Focusing on isotropic elastic networks we propose a simple-average expression G(t)=MU_{A}-h(t) for the computational determination of the shear-stress relaxation modulus G(t) of a classical elastic solid or fluid. Here, MU_{A}=G(0) characterizes the shear transformation of the system at t=0 and h(t) the (rescaled) mean-square displacement of the instantaneous shear stress tau[over ](t) as a function of time t. We discuss sampling time and ensemble effects and emphasize possible pitfalls of alternative expressions using the shear-stress autocorrelation function. We argue finally that our key relation may be readily adapted for more general linear response functions. PMID- 26871021 TI - Random-field Ising model on isometric lattices: Ground states and non-Porod scattering. AB - We use a computationally efficient graph cut method to obtain ground state morphologies of the random-field Ising model (RFIM) on (i) simple cubic (SC), (ii) body-centered cubic (BCC), and (iii) face-centered cubic (FCC) lattices. We determine the critical disorder strength Delta_{c} at zero temperature with high accuracy. For the SC lattice, our estimate (Delta_{c}=2.278+/-0.002) is consistent with earlier reports. For the BCC and FCC lattices, Delta_{c}=3.316+/ 0.002 and 5.160+/-0.002, respectively, which are the most accurate estimates in the literature to date. The small-r behavior of the correlation function exhibits a cusp regime characterized by a cusp exponent alpha signifying fractal interfaces. In the paramagnetic phase, alpha=0.5+/-0.01 for all three lattices. In the ferromagnetic phase, the cusp exponent shows small variations due to the lattice structure. Consequently, the interfacial energy E_{i}(L) for an interface of size L is significantly different for the three lattices. This has important implications for nonequilibrium properties. PMID- 26871022 TI - Hysteretic and intermittent regimes in the subcritical bifurcation of a quasi-one dimensional system of interacting particles. AB - In this article, we study the effects of white Gaussian additive thermal noise on a subcritical pitchfork bifurcation. We consider a quasi-one-dimensional system of particles that are transversally confined, with short-range (non-Coulombic) interactions and periodic boundary conditions in the longitudinal direction. In such systems, there is a structural transition from a linear order to a staggered row, called the zigzag transition. There is a finite range of transverse confinement stiffnesses for which the stable configuration at zero temperature is a localized zigzag pattern surrounded by aligned particles, which evidences the subcriticality of the bifurcation. We show that these configurations remain stable for a wide temperature range. At zero temperature, the transition between a straight line and such localized zigzag patterns is hysteretic. We have studied the influence of thermal noise on the hysteresis loop. Its description is more difficult than at T=0 K since thermally activated jumps between the two configurations always occur and the system cannot stay forever in a unique metastable state. Two different regimes have to be considered according to the temperature value with respect to a critical temperature T_{c}(tau_{obs}) that depends on the observation time tau_{obs}. An hysteresis loop is still observed at low temperature, with a width that decreases as the temperature increases toward T_{c}(tau_{obs}). In contrast, for T>T_{c}(tau_{obs}) the memory of the initial condition is lost by stochastic jumps between the configurations. The study of the mean residence times in each configuration gives a unique opportunity to precisely determine the barrier height that separates the two configurations, without knowing the complete energy landscape of this many-body system. We also show how to reconstruct the hysteresis loop that would exist at T=0 K from high-temperature simulations. PMID- 26871023 TI - Absence of absorbing phase transitions in a conserved lattice-gas model in one dimension. AB - A one-dimensional conserved lattice-gas model is known to undergo continuous absorbing phase transitions where some of the critical exponents are exactly known. In one dimension, we recently showed that the model is mapped onto a two species reaction A+B->0 with diffusion rate of D_{A}>0 and D_{B}=0. In this work, it is explicitly shown from the scaling theory for A+B->0 that the observed scaling behavior of the conserved lattice-gas model is not associated with the absorbing phase transitions. Instead, the model indeed undergoes a crossover between two different scaling behaviors of A+B->0, the scaling behaviors of equal and unequal initial densities of two species. The crossover is similar to the absorbing transitions in many respects but some important features of continuous transitions such as the diverging fluctuations of an order parameter are absent. PMID- 26871024 TI - Quantum phase transition in a coupled two-level system embedded in anisotropic three-dimensional photonic crystals. AB - The quantum phase transition (QPT) describes a sudden qualitative change of the macroscopic properties mapped from the eigenspectrum of a quantum many-body system. It has been studied intensively in quantum systems with the spin-boson model, but it has barely been explored for systems in coupled spin-boson models. In this paper, we study the QPT with coupled spin-boson models consisting of coupled two-level atoms embedded in three-dimensional anisotropic photonic crystals. The dynamics of the system is derived exactly by means of the Laplace transform method, which has been proven to be equivalent to the dissipationless non-Markovian dynamics. Drawing on methods for analyzing the ground state, we obtain the phase diagrams through two exact critical equations and two QPTs are found: one QPT is that from the phase without one bound state to the phase with one bound state and another is that from one phase with the bound state having one eigenvalue to another phase where the bound state has two eigenvalues. Our analytical results also suggest a way of control to overcome the effect of decoherence by engineering the spectrum of the reservoirs to approach the non Markovian regime and to form the bound state of the whole system for quantum devices and quantum statistics. PMID- 26871025 TI - Phase transition of anisotropic frustrated Heisenberg model on the square lattice. AB - We have investigated the J_{1}-J_{2} Heisenberg model with exchange anisotropy on a square lattice and focused on possible AF1-AF2 phase transition below the Neel point and its dependence on the exchange anisotropy, where AF1 and AF2 represent Neel state and collinear state, respectively. We use the double-time Green's function method and adopt the random-phase approximation. The less the exchange anisotropy, the stronger the quantum fluctuation of the system will be. Both the Neel state and collinear state can exist and have the same Neel temperature for arbitrary anisotropy and spin quantum number S when J_{2}/J_{1}=0.5. Under such parameters, the calculated free energies show that there may occur a first-order phase transition between the Neel state and collinear state for an arbitrary S when anisotropy is not strong. PMID- 26871026 TI - Superfluid phase transition with activated velocity fluctuations: Renormalization group approach. AB - A quantum field model that incorporates Bose-condensed systems near their phase transition into a superfluid phase and velocity fluctuations is proposed. The stochastic Navier-Stokes equation is used for a generation of the velocity fluctuations. As such this model generalizes model F of critical dynamics. The field-theoretic action is derived using the Martin-Siggia-Rose formalism and path integral approach. The regime of equilibrium fluctuations is analyzed within the perturbative renormalization group method. The double (epsilon,delta)-expansion scheme is employed, where epsilon is a deviation from space dimension 4 and delta describes scaling of velocity fluctuations. The renormalization procedure is performed to the leading order. The main corollary gained from the analysis of the thermal equilibrium regime suggests that one-loop calculations of the presented models are not sufficient to make a definite conclusion about the stability of fixed points. We also show that critical exponents are drastically changed as a result of the turbulent background and critical fluctuations are in fact destroyed by the developed turbulence fluctuations. The scaling exponent of effective viscosity is calculated and agrees with expected value 4/3. PMID- 26871027 TI - Continuous and discontinuous absorbing-state phase transitions on Voronoi Delaunay random lattices. AB - We study absorbing-state phase transitions (APTs) in two-dimensional Voronoi Delaunay (VD) random lattices with quenched coordination disorder. Quenched randomness usually changes the criticality and destroys discontinuous transitions in low-dimensional nonequilibrium systems. We performed extensive simulations of the Ziff-Gulari-Barshad model, and verified that the VD disorder does not change the nature of its discontinuous transition. Our results corroborate recent findings of Barghathi and Vojta [H. Barghathi and T. Vojta, Phys. Rev. Lett. 113, 120602 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.120602], stating the irrelevance of topological disorder in a class of random lattices that includes VD, and raise the interesting possibility that disorder in nonequilibrium APT may, under certain conditions, be irrelevant for the phase coexistence. We also verify that the VD disorder is irrelevant for the critical behavior of models belonging to the directed percolation and Manna universality classes. PMID- 26871028 TI - Nonequilibrium thermodynamic potentials for continuous-time Markov chains. AB - We connect the rare fluctuations of an equilibrium (EQ) process and the typical fluctuations of a nonequilibrium (NE) stationary process. In the framework of large deviation theory, this observation allows us to introduce NE thermodynamic potentials. For continuous-time Markov chains, we identify the relevant pairs of conjugated variables and propose two NE ensembles: one with fixed dynamics and fluctuating time-averaged variables, and another with fixed time-averaged variables, but a fluctuating dynamics. Accordingly, we show that NE processes are equivalent to conditioned EQ processes ensuring that NE potentials are Legendre dual. We find a variational principle satisfied by the NE potentials that reach their maximum in the NE stationary state and whose first derivatives produce the NE equations of state and second derivatives produce the NE Maxwell relations generalizing the Onsager reciprocity relations. PMID- 26871030 TI - Macroscopic time-reversal symmetry breaking at a nonequilibrium phase transition. AB - We study the entropy production in a globally coupled Brownian particles system that undergoes an order-disorder phase transition. Entropy production is a characteristic feature of nonequilibrium dynamics with broken detailed balance. We find that the entropy production rate is subextensive in the disordered phase and extensive in the ordered phase. It is found that the entropy production rate per particle vanishes in the disordered phase and becomes positive in the ordered phase following critical scaling laws. We derive the scaling relations for associated critical exponents. The disordered phase exemplifies a case where the entropy production is subextensive with the broken detailed balance. PMID- 26871029 TI - Kinetic theory of age-structured stochastic birth-death processes. AB - Classical age-structured mass-action models such as the McKendrick-von Foerster equation have been extensively studied but are unable to describe stochastic fluctuations or population-size-dependent birth and death rates. Stochastic theories that treat semi-Markov age-dependent processes using, e.g., the Bellman Harris equation do not resolve a population's age structure and are unable to quantify population-size dependencies. Conversely, current theories that include size-dependent population dynamics (e.g., mathematical models that include carrying capacity such as the logistic equation) cannot be easily extended to take into account age-dependent birth and death rates. In this paper, we present a systematic derivation of a new, fully stochastic kinetic theory for interacting age-structured populations. By defining multiparticle probability density functions, we derive a hierarchy of kinetic equations for the stochastic evolution of an aging population undergoing birth and death. We show that the fully stochastic age-dependent birth-death process precludes factorization of the corresponding probability densities, which then must be solved by using a Bogoliubov--Born--Green--Kirkwood--Yvon-like hierarchy. Explicit solutions are derived in three limits: no birth, no death, and steady state. These are then compared with their corresponding mean-field results. Our results generalize both deterministic models and existing master equation approaches by providing an intuitive and efficient way to simultaneously model age- and population-dependent stochastic dynamics applicable to the study of demography, stem cell dynamics, and disease evolution. PMID- 26871032 TI - Coulomb potential V(r)=1/r problem on the Bethe lattice. AB - We study the problem of a particle hopping on the Bethe lattice in the presence of a Coulomb potential. We obtain an exact solution to the particle's Green's function along with the full energy spectrum. In addition, we present a mapping of a generalized radial potential problem defined on the Bethe lattice to an infinite number of one-dimensional problems that are easily accessible numerically. The latter method is particularly useful when the problem admits no analytical solution. PMID- 26871031 TI - Large fluctuations and singular behavior of nonequilibrium systems. AB - We present a general geometrical approach to the problem of escape from a metastable state in the presence of noise. The accompanying analysis leads to a simple condition, based on the norm of the drift field, for determining whether caustic singularities alter the escape trajectories when detailed balance is absent. We apply our methods to systems lacking detailed balance, including a nanomagnet with a biaxial magnetic anisotropy and subject to a spin-transfer torque. The approach described within allows determination of the regions of experimental parameter space that admit caustics. PMID- 26871033 TI - Connectivity percolation in suspensions of attractive square-well spherocylinders. AB - We have studied the connectivity percolation transition in suspensions of attractive square-well spherocylinders by means of Monte Carlo simulation and connectedness percolation theory. In the 1980s the percolation threshold of slender fibers has been predicted to scale as the fibers' inverse aspect ratio [Phys. Rev. B 30, 3933 (1984)PRBMDO1098-012110.1103/PhysRevB.30.3933]. The main finding of our study is that the attractive spherocylinder system reaches this inverse scaling regime at much lower aspect ratios than found in suspensions of hard spherocylinders. We explain this difference by showing that third virial corrections of the pair connectedness functions, which are responsible for the deviation from the scaling regime, are less important for attractive potentials than for hard particles. PMID- 26871034 TI - Order-parameter scaling in fluctuation-dominated phase ordering. AB - In systems exhibiting fluctuation-dominated phase ordering, a single order parameter does not suffice to characterize the order, and it is necessary to monitor a larger set. For hard-core sliding particles on a fluctuating surface and the related coarse-grained depth (CD) models, this set comprises the long wavelength Fourier components of the density profile, which capture the breakup and remerging of particle-rich regions. We study both static and dynamic scaling laws obeyed by the Fourier modes Q_{mL} and find that the mean value obeys the static scaling law ~L^{-phi}f(m/L) with phi?2/3 and phi?3/5 for Edwards Wilkinson (EW) and Kardar-Parisi-Zhang (KPZ) surface evolution, respectively, and phi?3/4 for the CD model. The full probability distribution P(Q_{mL}) exhibits scaling as well. Further, time-dependent correlation functions such as the steady state autocorrelation and cross-correlations of order-parameter components are scaling functions of t/L^{z}, where L is the system size and z is the dynamic exponent, with z=2 for EW and z=3/2 for KPZ surface evolution. In addition we find that the CD model shows temporal intermittency, manifested in the dynamical structure functions of the density and the weak divergence of the flatness as the scaled time approaches 0. PMID- 26871035 TI - Non-self-averaging in Ising spin glasses and hyperuniversality. AB - Ising spin glasses with bimodal and Gaussian near-neighbor interaction distributions are studied through numerical simulations. The non-self-averaging (normalized intersample variance) parameter U_{22}(T,L) for the spin glass susceptibility [and for higher moments U_{nn}(T,L)] is reported for dimensions 2,3,4,5, and 7. In each dimension d the non-self-averaging parameters in the paramagnetic regime vary with the sample size L and the correlation length xi(T,L) as U_{nn}(beta,L)=[K_{d}xi(T,L)/L]^{d} and so follow a renormalization group law due to Aharony and Harris [Phys. Rev. Lett. 77, 3700 (1996)PRLTAO0031 900710.1103/PhysRevLett.77.3700]. Empirically, it is found that the K_{d} values are independent of d to within the statistics. The maximum values [U_{nn}(T,L)]_{max} are almost independent of L in each dimension, and remarkably the estimated thermodynamic limit critical [U_{nn}(T,L)]_{max} peak values are also practically dimension-independent to within the statistics and so are "hyperuniversal." These results show that the form of the spin-spin correlation function distribution at criticality in the large L limit is independent of dimension within the ISG family. Inspection of published non-self-averaging data for three-dimensional Heisenberg and XY spin glasses the light of the Ising spin glass non-self-averaging results show behavior which appears to be compatible with that expected on a chiral-driven ordering interpretation but incompatible with a spin-driven ordering scenario. PMID- 26871036 TI - On-site residence time in a driven diffusive system: Violation and recovery of a mean-field description. AB - We investigate simple one-dimensional driven diffusive systems with open boundaries. We are interested in the average on-site residence time defined as the time a particle spends on a given site before moving on to the next site. Using mean-field theory, we obtain an analytical expression for the on-site residence times. By comparing the analytic predictions with numerics, we demonstrate that the mean-field significantly underestimates the residence time due to the neglect of time correlations in the local density of particles. The temporal correlations are particularly long-lived near the average shock position, where the density changes abruptly from low to high. By using domain wall theory, we obtain highly accurate estimates of the residence time for different boundary conditions. We apply our analytical approach to residence times in a totally asymmetric exclusion process (TASEP), TASEP coupled to Langmuir kinetics (TASEP+LK), and TASEP coupled to mutually interactive LK (TASEP+MILK). The high accuracy of our predictions is verified by comparing these with detailed Monte Carlo simulations. PMID- 26871037 TI - Optimizing work output for finite-sized heat reservoirs: Beyond linear response. AB - We uncover an optimization principle for the finite-time heat-work conversion process performed between two finite-sized heat reservoirs in the nonlinear response regime that is characterized by rather generic flux-force relations. We solve the problem of maximizing work output in a given time interval by means of the variational method. Moreover, in the limiting case that the cold reservoir is infinite, we find the corresponding optimized process can be determined by a single quantity, which plays the role similar to that of the Hamiltonian in classical mechanics. Some theoretical implications are discussed consequently, under the generalized tight-coupling condition which applies to both linear and nonlinear response cases. Our results can hopefully help design and control realistic thermodynamical processes. PMID- 26871038 TI - Thermostatistics of small nonlinear systems: Poissonian athermal bath. AB - We extend an earlier study [W. A. M. Morgado and S. M. Duarte Queiros, Phys. Rev. E 90, 022110 (2014)PLEEE81539-375510.1103/PhysRevE.90.022110] to the case of a small system subject to nonlinear interaction and in contact with an athermal shot-noise reservoir. We first focus on steady state properties, namely, on the impact of the singular measure of the reservoir in the steady state energy. We introduce the concept of temperatures of higher order, which aim to represent the effect produced by the cumulants of the noise of order larger than 2 in the form of sources of energy of higher order and new response functions such as high order specific heats that zero out when the system is thermal or linear. Afterwards, we study the effect of the nature of the noise in the heat and energy fluxes and determine asymptotic expressions for its large deviation functions. Finally, by analyzing the probabilistics of the injected power, we verify that the exponential form of its fluctuation relation is only asymptotically valid, whereas in the thermal case it is valid for the injected power at all times. PMID- 26871039 TI - Nonstationary Feller process with time-varying coefficients. AB - We study the nonstationary Feller process with time varying coefficients. We obtain the exact probability distribution exemplified by its characteristic function and cumulants. In some particular cases we exactly invert the distribution and achieve the probability density function. We show that for sufficiently long times this density approaches a Gamma distribution with time varying shape and scale parameters. Not far from the origin the process obeys a power law with an exponent dependent of time, thereby concluding that accessibility to the origin is not static but dynamic. We finally discuss some possible applications of the process. PMID- 26871040 TI - Dynamical phase transitions in totally asymmetric simple exclusion processes with two types of particles under periodically driven boundary conditions. AB - Driven diffusive systems have provided simple models for nonequilibrium systems with nontrivial structures. Steady-state behavior of these systems with constant boundary conditions have been studied extensively. Comparatively less work has been carried out on the responses of these systems to time-dependent parameters. We report the modifications to the probability density function of a two-particle exclusion model in response to a periodically changing perturbation to its boundary conditions. The changes in the shape of the distribution as a function of the frequency of the perturbation contains considerable structure. A dynamical phase transition in which the system response changes abruptly as a function of perturbation frequency was observed. We interpret this structure to be a consequence of the existence of a typical time scale associated with the dynamics of density shock profiles within the system. PMID- 26871041 TI - Minimal exactly solved model with the extreme Thouless effect. AB - We present and analyze a minimal exactly solved model that exhibits a mixed-order phase transition known in the literature as the Thouless effect. Such hybrid transitions do not fit into the modest classification of thermodynamic transitions and, as such, they used to be overlooked or incorrectly identified in the past. The recent series of observations of such transitions in many diverse systems suggest that a new taxonomy of phase transitions is needed. The spin model we present due to its simplicity and possible experimental designs could bring us to this goal. We find the Hamiltonian of the model from which partition function is easily calculated. Thermodynamic properties of the model, i.e., discontinuous magnetization and diverging susceptibility, are discussed. Finally, its generalizations and further research directions are proposed. PMID- 26871042 TI - Numerical evidence for approximate consistency and Markovianity of some quantum histories in a class of finite closed spin systems. AB - Closed quantum systems obey the Schrodinger equation, whereas nonequilibrium behavior of many systems is routinely described in terms of classical, Markovian stochastic processes. Evidently, there are fundamental differences between those two types of behavior. We discuss the conditions under which the unitary dynamics may be mapped onto pertinent classical stochastic processes. This is first principally addressed based on the notions of "consistency" and "Markovianity." Numerical data are presented that show that the above conditions are to good approximation fulfilled for Heisenberg-type spin models comprising 12-20 spins. The accuracy to which these conditions are met increases with system size. PMID- 26871043 TI - Dynamical thermalization in Bose-Hubbard systems. AB - We numerically study a Bose-Hubbard ring of finite size with disorder containing a finite number of bosons that are subject to an on-site two-body interaction. Our results show that moderate interactions induce dynamical thermalization in this isolated system. In this regime the individual many-body eigenstates are well described by the standard thermal Bose-Einstein distribution for well defined values of the temperature and the chemical potential, which depend on the eigenstate under consideration. We show that the dynamical thermalization conjecture works well at both positive and negative temperatures. The relations to quantum chaos, quantum ergodicity, and the Aberg criterion are also discussed. PMID- 26871044 TI - Calculating work in weakly driven quantum master equations: Backward and forward equations. AB - I present a technical report indicating that the two methods used for calculating characteristic functions for the work distribution in weakly driven quantum master equations are equivalent. One involves applying the notion of quantum jump trajectory [Phys. Rev. E 89, 042122 (2014)PLEEE81539 375510.1103/PhysRevE.89.042122], while the other is based on two energy measurements on the combined system and reservoir [Silaev et al., Phys. Rev. E 90, 022103 (2014)PLEEE81539-375510.1103/PhysRevE.90.022103]. These represent backward and forward methods, respectively, which adopt a very similar approach to that of the Kolmogorov backward and forward equations used in classical stochastic theory. The microscopic basis for the former method is also clarified. In addition, a previously unnoticed equality related to the heat is also revealed. PMID- 26871045 TI - Probability-current analysis of energy transport in open quantum systems. AB - We introduce a probability-current analysis of excitation energy transfer between states of an open quantum system. Expressing the energy transfer through currents of excitation probability between the states in a site representation enables us to gain key insights into the energy transfer dynamics. In particular, the analysis yields direct identification of the pathways of energy transport in large networks of sites and quantifies their relative weights, as well as the respective contributions of unitary dynamics, coherence, dephasing, and relaxation and dissipation processes to the energy transfer. It thus provides much more information than studying only excitation probabilities of the states as a function of time. Our analysis is general and can be readily applied to a broad range of dynamical descriptions of open quantum system dynamics with coupling to non-Markovian or Markovian environments. PMID- 26871046 TI - Conflict between fastest relaxation of a Markov process and detailed balance condition. AB - We consider the optimization of Markovian dynamics to pursue the fastest convergence to the stationary state. The brachistochrone method is applied to the continuous-time master equation for finite-size systems. The principle of least action leads to a brachistochrone equation for the transition-rate matrix. Three state systems are explicitly analyzed, and we find that the solution violates the detailed balance condition. The properties of the solution are studied in detail to observe the optimality of the solution. We also discuss the counterdiabatic driving for the Markovian dynamics. The transition-rate matrix is then divided into two parts, and the state is given by an eigenstate of the first part. The second part violates the detailed balance condition and plays the role of a counterdiabatic term. PMID- 26871047 TI - Stroboscopic prethermalization in weakly interacting periodically driven systems. AB - Time-periodic driving provides a promising route toward engineering nontrivial states in quantum many-body systems. However, while it has been shown that the dynamics of integrable, noninteracting systems can synchronize with the driving into a nontrivial periodic motion, generic nonintegrable systems are expected to heat up until they display a trivial infinite-temperature behavior. In this paper we show that a quasiperiodic time evolution over many periods can also emerge in weakly interacting systems, with a clear separation of the timescales for synchronization and the eventual approach of the infinite-temperature state. This behavior is the analog of prethermalization in quenched systems. The synchronized state can be described using a macroscopic number of approximate constants of motion. We corroborate these findings with numerical simulations for the driven Hubbard model. PMID- 26871048 TI - Quantum discord length is enhanced while entanglement length is not by introducing disorder in a spin chain. AB - Classical correlation functions of ground states typically decay exponentially and polynomially, respectively, for gapped and gapless short-range quantum spin systems. In such systems, entanglement decays exponentially even at the quantum critical points. However, quantum discord, an information-theoretic quantum correlation measure, survives long lattice distances. We investigate the effects of quenched disorder on quantum correlation lengths of quenched averaged entanglement and quantum discord, in the anisotropic XY and XYZ spin glass and random field chains. We find that there is virtually neither reduction nor enhancement in entanglement length while quantum discord length increases significantly with the introduction of the quenched disorder. PMID- 26871049 TI - Entropy production of a Brownian ellipsoid in the overdamped limit. AB - We analyze the translational and rotational motion of an ellipsoidal Brownian particle from the viewpoint of stochastic thermodynamics. The particle's Brownian motion is driven by external forces and torques and takes place in an heterogeneous thermal environment where friction coefficients and (local) temperature depend on space and time. Our analysis of the particle's stochastic thermodynamics is based on the entropy production associated with single particle trajectories. It is motivated by the recent discovery that the overdamped limit of vanishing inertia effects (as compared to viscous fricion) produces a so called "anomalous" contribution to the entropy production, which has no counterpart in the overdamped approximation, when inertia effects are simply discarded. Here we show that rotational Brownian motion in the overdamped limit generates an additional contribution to the "anomalous" entropy. We calculate its specific form by performing a systematic singular perturbation analysis for the generating function of the entropy production. As a side result, we also obtain the (well-known) equations of motion in the overdamped limit. We furthermore investigate the effects of particle shape and give explicit expressions of the "anomalous entropy" for prolate and oblate spheroids and for near-spherical Brownian particles. PMID- 26871050 TI - Gauge invariance and geometric phase in nonequilibrium thermodynamics. AB - We show the link between U(1) lattice gauge theories and the off-equilibrium thermodynamics of a large class of nonlinear oscillators networks. The coupling between the oscillators plays the role of a gauge field, or connection, on the network. The thermodynamical forces that drive energy flows are expressed in terms of the curvature of the connection, analogous to a geometric phase. The model, which holds both close and far from equilibrium, predicts the existence of persistent energy and particle currents circulating in closed loops through the network. The predictions are confirmed by numerical simulations. Possible extension of the theory and experimental applications to nanoscale devices are briefly discussed. PMID- 26871051 TI - From single-file diffusion to two-dimensional cage diffusion and generalization of the totally asymmetric simple exclusion process to higher dimensions. AB - A two-dimensional constrained diffusion model is presented and characterized by numerical simulations. The model generalizes the one-dimensional single-file diffusion model by considering a cage diffusion constraint induced by neighboring particles, which is a more stringent condition than volume exclusion. Using numerical simulations we characterize the diffusion process and we particularly show that asymmetric transition probabilities lead to the two-dimensional Kardar Parisi-Zhang universality class. Therefore, this very simple model effectively generalizes the one-dimensional totally asymmetric simple exclusion process to higher dimensions. PMID- 26871052 TI - Lloyd-model generalization: Conductance fluctuations in one-dimensional disordered systems. AB - We perform a detailed numerical study of the conductance G through one dimensional (1D) tight-binding wires with on-site disorder. The random configurations of the on-site energies epsilon of the tight-binding Hamiltonian are characterized by long-tailed distributions: For large epsilon, P(epsilon)~1/epsilon^{1+alpha} with alpha?(0,2). Our model serves as a generalization of the 1D Lloyd model, which corresponds to alpha=1. First, we verify that the ensemble average <-lnG> is proportional to the length of the wire L for all values of alpha, providing the localization length xi from < lnG>=2L/xi. Then, we show that the probability distribution function P(G) is fully determined by the exponent alpha and <-lnG>. In contrast to 1D wires with standard white-noise disorder, our wire model exhibits bimodal distributions of the conductance with peaks at G=0 and 1. In addition, we show that P(lnG) is proportional to G^{beta}, for G->0, with beta<=alpha/2, in agreement with previous studies. PMID- 26871054 TI - Steepest-entropy-ascent quantum thermodynamic modeling of the relaxation process of isolated chemically reactive systems using density of states and the concept of hypoequilibrium state. AB - This paper presents a study of the nonequilibrium relaxation process of chemically reactive systems using steepest-entropy-ascent quantum thermodynamics (SEAQT). The trajectory of the chemical reaction, i.e., the accessible intermediate states, is predicted and discussed. The prediction is made using a thermodynamic-ensemble approach, which does not require detailed information about the particle mechanics involved (e.g., the collision of particles). Instead, modeling the kinetics and dynamics of the relaxation process is based on the principle of steepest-entropy ascent (SEA) or maximum-entropy production, which suggests a constrained gradient dynamics in state space. The SEAQT framework is based on general definitions for energy and entropy and at least theoretically enables the prediction of the nonequilibrium relaxation of system state at all temporal and spatial scales. However, to make this not just theoretically but computationally possible, the concept of density of states is introduced to simplify the application of the relaxation model, which in effect extends the application of the SEAQT framework even to infinite energy eigenlevel systems. The energy eigenstructure of the reactive system considered here consists of an extremely large number of such levels (on the order of 10^{130}) and yields to the quasicontinuous assumption. The principle of SEA results in a unique trajectory of system thermodynamic state evolution in Hilbert space in the nonequilibrium realm, even far from equilibrium. To describe this trajectory, the concepts of subsystem hypoequilibrium state and temperature are introduced and used to characterize each system-level, nonequilibrium state. This definition of temperature is fundamental rather than phenomenological and is a generalization of the temperature defined at stable equilibrium. In addition, to deal with the large number of energy eigenlevels, the equation of motion is formulated on the basis of the density of states and a set of associated degeneracies. Their significance for the nonequilibrium evolution of system state is discussed. For the application presented, the numerical method used is described and is based on the density of states, which is specifically developed to solve the SEAQT equation of motion. Results for different kinds of initial nonequilibrium conditions, i.e., those for gamma and Maxwellian distributions, are studied. The advantage of the concept of hypoequilibrium state in studying nonequilibrium trajectories is discussed. PMID- 26871053 TI - Survival of interacting diffusing particles inside a domain with absorbing boundary. AB - Suppose that a d-dimensional domain is filled with a gas of (in general, interacting) diffusive particles with density n_{0}. A particle is absorbed whenever it reaches the domain boundary. Employing macroscopic fluctuation theory, we evaluate the probability P that no particles are absorbed during a long time T. We argue that the most likely gas density profile, conditional on this event, is stationary throughout most of the time T. As a result, P decays exponentially with T for a whole class of interacting diffusive gases in any dimension. For d=1 the stationary gas density profile and P can be found analytically. In higher dimensions we focus on the simple symmetric exclusion process (SSEP) and show that -lnP?D_{0}TL^{d-2}s(n_{0}), where D_{0} is the gas diffusivity, and L is the linear size of the system. We calculate the rescaled action s(n_{0}) for d=1, for rectangular domains in d=2, and for spherical domains. Near close packing of the SSEP s(n_{0}) can be found analytically for domains of any shape and in any dimension. PMID- 26871055 TI - Fine structure of the entanglement entropy in the O(2) model. AB - We compare two calculations of the particle density in the superfluid phase of the O(2) model with a chemical potential MU in 1+1 dimensions. The first relies on exact blocking formulas from the Tensor Renormalization Group (TRG) formulation of the transfer matrix. The second is a worm algorithm. We show that the particle number distributions obtained with the two methods agree well. We use the TRG method to calculate the thermal entropy and the entanglement entropy. We describe the particle density, the two entropies and the topology of the world lines as we increase MU to go across the superfluid phase between the first two Mott insulating phases. For a sufficiently large temporal size, this process reveals an interesting fine structure: the average particle number and the winding number of most of the world lines in the Euclidean time direction increase by one unit at a time. At each step, the thermal entropy develops a peak and the entanglement entropy increases until we reach half-filling and then decreases in a way that approximately mirrors the ascent. This suggests an approximate fermionic picture. PMID- 26871056 TI - Pattern density function for reconstruction of three-dimensional porous media from a single two-dimensional image. AB - Three-dimensional (3D) structures are useful for studying the spatial structures and physical properties of porous media. A 3D structure can be reconstructed from a single two-dimensional (2D) training image (TI) by using mathematical modeling methods. Among many reconstruction algorithms, an optimal-based algorithm was developed and has strong stability. However, this type of algorithm generally uses an autocorrelation function (which is unable to accurately describe the morphological features of porous media) as its objective function. This has negatively affected further research on porous media. To accurately reconstruct 3D porous media, a pattern density function is proposed in this paper, which is based on a random variable employed to characterize image patterns. In addition, the paper proposes an original optimal-based algorithm called the pattern density function simulation; this algorithm uses a pattern density function as its objective function, and adopts a multiple-grid system. Meanwhile, to address the key point of algorithm reconstruction speed, we propose the use of neighborhood statistics, the adjacent grid and reversed phase method, and a simplified temperature-controlled mechanism. The pattern density function is a high-order statistical function; thus, when all grids in the reconstruction results converge in the objective functions, the morphological features and statistical properties of the reconstruction results will be consistent with those of the TI. The experiments include 2D reconstruction using one artificial structure, and 3D reconstruction using battery materials and cores. Hierarchical simulated annealing and single normal equation simulation are employed as the comparison algorithms. The autocorrelation function, linear path function, and pore network model are used as the quantitative measures. Comprehensive tests show that 3D porous media can be reconstructed accurately from a single 2D training image by using the method proposed in this paper. PMID- 26871057 TI - Phase transition of the Ising model on a fractal lattice. AB - The phase transition of the Ising model is investigated on a planar lattice that has a fractal structure. On the lattice, the number of bonds that cross the border of a finite area is doubled when the linear size of the area is extended by a factor of 4. The free energy and the spontaneous magnetization of the system are obtained by means of the higher-order tensor renormalization group method. The system exhibits the order-disorder phase transition, where the critical indices are different from those of the square-lattice Ising model. An exponential decay is observed in the density-matrix spectrum even at the critical point. It is possible to interpret that the system is less entangled because of the fractal geometry. PMID- 26871058 TI - Efficiency at maximum power of a discrete feedback ratchet. AB - Efficiency at maximum power is found to be of the same order for a feedback ratchet and for its open-loop counterpart. However, feedback increases the output power up to a factor of five. This increase in output power is due to the increase in energy input and the effective entropy reduction obtained as a consequence of feedback. Optimal efficiency at maximum power is reached for time intervals between feedback actions two orders of magnitude smaller than the characteristic time of diffusion over a ratchet period length. The efficiency is computed consistently taking into account the correlation between the control actions. We consider a feedback control protocol for a discrete feedback flashing ratchet, which works against an external load. We maximize the power output optimizing the parameters of the ratchet, the controller, and the external load. The maximum power output is found to be upper bounded, so the attainable extracted power is limited. After, we compute an upper bound for the efficiency of this isothermal feedback ratchet at maximum power output. We make this computation applying recent developments of the thermodynamics of feedback controlled systems, which give an equation to compute the entropy reduction due to information. However, this equation requires the computation of the probability of each of the possible sequences of the controller's actions. This computation becomes involved when the sequence of the controller's actions is non Markovian, as is the case in most feedback ratchets. We here introduce an alternative procedure to set strong bounds to the entropy reduction in order to compute its value. In this procedure the bounds are evaluated in a quasi Markovian limit, which emerge when there are big differences between the stationary probabilities of the system states. These big differences are an effect of the potential strength, which minimizes the departures from the Markovianicity of the sequence of control actions, allowing also to minimize the departures from the optimal performance of the system. This procedure can be applied to other feedback ratchets and, more in general, to other control systems. PMID- 26871059 TI - Phase transitions and entropies for synchronizing oscillators. AB - We study a generic model of coupled oscillators. In the model there is competition between phase synchronization and diffusive effects. For a model with a finite number of states we derive how a phase transition occurs when the coupling parameter is varied. The phase transition is characterized by a symmetry breaking and a discontinuity in the first derivative of the order parameter. We quantitatively account for how the synchronized pulse is a low-entropy structure that facilitates the production of more entropy by the system as a whole. For a model with many states we apply a continuum approximation and derive a potential Burgers' equation for a propagating pulse. No phase transition occurs in that case. However, positive entropy production by diffusive effects still exceeds negative entropy production by the shock formation. PMID- 26871060 TI - Scale invariance implies conformal invariance for the three-dimensional Ising model. AB - Using the Wilson renormalization group, we show that if no integrated vector operator of scaling dimension -1 exists, then scale invariance implies conformal invariance. By using the Lebowitz inequalities, we prove that this necessary condition is fulfilled in all dimensions for the Ising universality class. This shows, in particular, that scale invariance implies conformal invariance for the three-dimensional Ising model. PMID- 26871061 TI - Quantum fuel with multilevel atomic coherence for ultrahigh specific work in a photonic Carnot engine. AB - We investigate scaling of work and efficiency of a photonic Carnot engine with a number of quantum coherent resources. Specifically, we consider a generalization of the "phaseonium fuel" for the photonic Carnot engine, which was first introduced as a three-level atom with two lower states in a quantum coherent superposition by M. O. Scully, M. Suhail Zubairy, G. S. Agarwal, and H. Walther [Science 299, 862 (2003)SCIEAS0036-807510.1126/science.1078955], to the case of N+1 level atoms with N coherent lower levels. We take into account atomic relaxation and dephasing as well as the cavity loss and derive a coarse-grained master equation to evaluate the work and efficiency analytically. Analytical results are verified by microscopic numerical examination of the thermalization dynamics. We find that efficiency and work scale quadratically with the number of quantum coherent levels. Quantum coherence boost to the specific energy (work output per unit mass of the resource) is a profound fundamental difference of quantum fuel from classical resources. We consider typical modern resonator set ups and conclude that multilevel phaseonium fuel can be utilized to overcome the decoherence in available systems. Preparation of the atomic coherences and the associated cost of coherence are analyzed and the engine operation within the bounds of the second law is verified. Our results bring the photonic Carnot engines much closer to the capabilities of current resonator technologies. PMID- 26871062 TI - Effect of geometrical frustration on inverse freezing. AB - The interplay between geometrical frustration (GF) and inverse freezing (IF) is studied within a cluster approach. The model considers first-neighbor (J_{1}) and second-neighbor (J_{2}) intracluster antiferromagnetic interactions between Ising spins on a checkerboard lattice and long-range disordered couplings (J) among clusters. We obtain phase diagrams of temperature versus J_{1}/J in two cases: the absence of J_{2} interaction and the isotropic limit J_{2}=J_{1}, where GF takes place. An IF reentrant transition from the spin-glass (SG) to paramagnetic (PM) phase is found for a certain range of J_{1}/J in both cases. The J_{1} interaction leads to a SG state with high entropy at the same time that can introduce a low-entropy PM phase. In addition, it is observed that the cluster size plays an important role. The GF increases the PM phase entropy, but larger clusters can give an entropic advantage for the SG phase that favors IF. Therefore, our results suggest that disordered systems with antiferromagnetic clusters can exhibit an IF transition even in the presence of GF. PMID- 26871063 TI - Physical origin of nonequilibrium fluctuation-induced forces in fluids. AB - Long-range thermal fluctuations appear in fluids in nonequilibrium states leading to fluctuation-induced Casimir-like forces. Two distinct mechanisms have been identified for the origin of the long-range nonequilibrium fluctuations in fluids subjected to a temperature or concentration gradient. One is a coupling between the heat or mass-diffusion mode with a viscous mode in fluids subjected to a temperature or concentration gradient. Another one is the spatial inhomogeneity of thermal noise in the presence of a gradient. We show that in fluids fluctuation-induced forces arising from mode coupling are several orders of magnitude larger than those from inhomogeneous noise. PMID- 26871064 TI - Experimental study of stable imbibition displacements in a model open fracture. I. Local avalanche dynamics. AB - We report the results of an experimental investigation of the spatiotemporal dynamics of stable imbibition fronts in a disordered medium, in the regime of capillary disorder, for a wide range of experimental conditions. We have used silicone oils of various viscosities MU and nearly identical oil-air surface tension and forced them to slowly invade a model open fracture at different constant flow rates v. In this first part of the study we have focused on the local dynamics at a scale below the size of the quenched disorder. Changing MU and v independently, we have found that the dynamics is not simply controlled by the capillary number Ca~MUv. Specifically, we have found that the wide statistical distributions of local front velocities, and their large spatial correlations along the front, are indeed controlled by the capillary number Ca. However, local velocities exhibit also very large temporal correlations, and these correlations depend more strongly on the mean imposed velocity v than on the viscosity MU of the invading fluid. Correlations between local velocities lead to a burstlike dynamics. Avalanches, defined as clusters of large local velocities, follow power-law distributions-both in size and duration-with exponential cutoffs that diverge as Ca->0, the pinning-depinning transition of stable imbibition displacements. Large data sets have led to reliable statistics, from which we have derived accurate values of critical exponents of the relevant power-law distributions. We have investigated also the dependence of their cutoffs on MU and v and related them to the autocorrelations of local velocities in space and time. PMID- 26871065 TI - Experimental study of stable imbibition displacements in a model open fracture. II. Scale-dependent avalanche dynamics. AB - We report the results of an experimental investigation of the spatiotemporal dynamics of stable imbibition fronts in a disordered medium, in the regime of capillary disorder, for a wide range of experimental conditions. We have used silicone oils of various viscosities MU and nearly identical oil-air surface tension, and forced them to slowly invade a model open fracture at very different flow rates v. In this second part of the study we have carried out a scale dependent statistical analysis of the front dynamics. We have specifically analyzed the influence of MU and v on the statistical properties of the velocity V_{l}, the spatial average of the local front velocities over a window of lateral size l. We have varied l from the local scale defined by our spatial resolution up to the lateral system size L. Even though the imposed flow rate is constant, the signals V_{l}(t) present very strong fluctuations which evolve systematically with the parameters MU, v, and l. We have verified that the non-Gaussian fluctuations of the global velocity V_{l}(t) are very well described by a generalized Gumbel statistics. The asymmetric shape and the exponential tail of those distributions are controlled by the number of effective degrees of freedom of the imbibition fronts, given by N_{eff}=l/l_{c} (the ratio of the lateral size of the measuring window l to the correlation length l_{c}~1/sqrt[MUv]). The large correlated excursions of V_{l}(t) correspond to global avalanches, which reflect extra displacements of the imbibition fronts. We show that global avalanches are power-law distributed, both in sizes and durations, with robustly defined exponents-independent of MU, v, and l. Nevertheless, the exponential upper cutoffs of the distributions evolve systematically with those parameters. We have found, moreover, that maximum sizes xi_{S} and maximum durations xi_{T} of global avalanches are not controlled by the same mechanism. While xi_{S} are also determined by l/l_{c}, like the amplitude fluctuations of V_{l}(t), xi_{T} and the temporal correlations of V_{l}(t) evolve much more strongly with imposed flow rate v than with fluid viscosity MU. PMID- 26871066 TI - Directed percolation process in the presence of velocity fluctuations: Effect of compressibility and finite correlation time. AB - The direct bond percolation process (Gribov process) is studied in the presence of random velocity fluctuations generated by the Gaussian self-similar ensemble with finite correlation time. We employ the renormalization group in order to analyze a combined effect of the compressibility and finite correlation time on the long-time behavior of the phase transition between an active and an absorbing state. The renormalization procedure is performed to the one-loop order. Stable fixed points of the renormalization group and their regions of stability are calculated in the one-loop approximation within the three-parameter (E,y,eta) expansion. Different regimes corresponding to the rapid-change limit and frozen velocity field are discussed, and their fixed points' structure is determined in numerical fashion. PMID- 26871067 TI - Resonant torus-assisted tunneling. AB - We report a new type of dynamical tunneling, which is mediated by a resonant torus, i.e., a nonisolated periodic orbit. To elucidate the phenomenon, we take an open elliptic cavity and show that a pair of resonances localized on two classically disconnected tori tunnel through a resonant torus when they interact with each other. This so-called resonant torus-assisted tunneling is verified by using Husimi functions, corresponding actions, Husimi function distributions, and the standard deviations of the actions. PMID- 26871068 TI - Uniform framework for the recurrence-network analysis of chaotic time series. AB - We propose a general method for the construction and analysis of unweighted epsilon-recurrence networks from chaotic time series. The selection of the critical threshold epsilon_{c} in our scheme is done empirically and we show that its value is closely linked to the embedding dimension M. In fact, we are able to identify a small critical range Deltaepsilon numerically that is approximately the same for the random and several standard chaotic time series for a fixed M. This provides us a uniform framework for the nonsubjective comparison of the statistical measures of the recurrence networks constructed from various chaotic attractors. We explicitly show that the degree distribution of the recurrence network constructed by our scheme is characteristic to the structure of the attractor and display statistical scale invariance with respect to increase in the number of nodes N. We also present two practical applications of the scheme, detection of transition between two dynamical regimes in a time-delayed system and identification of the dimensionality of the underlying system from real-world data with a limited number of points through recurrence network measures. The merits, limitations, and the potential applications of the proposed method are also highlighted. PMID- 26871069 TI - Energy shell structure in a dielectric elliptic microcavity. AB - An energy shell structure depending on eccentricity is analyzed in a dielectric elliptic microcavity. Through the analysis, it is explicated that the energy shell structure is governed by classical constant actions of periodic orbits. For clarification, the relation between dominances of the periodic orbits and bifurcation behaviors are obtained and the length spectra based on eigenvalues computed by a numerical method are compared with the exact lengths of the periodic orbits obtained by analytic calculations. By matching effective wave numbers obtained from the periodic orbit lengths to exact wave numbers of stationary states in closed and open cavities, we find deviations provoked from the openness. We show that these deviations are caused by additional phase factors in the Einstein-Brillouin-Keller quantization. PMID- 26871070 TI - Chaos in the honeycomb optical-lattice unit cell. AB - Natural and artificial honeycomb lattices are of great interest because the band structure of these lattices, if properly constructed, contains a Dirac point. Such lattices occur naturally in the form of graphene and carbon nanotubes. They have been created in the laboratory in the form of semiconductor 2DEGs, optical lattices, and photonic crystals. We show that, over a wide energy range, gases (of electrons, atoms, or photons) that propagate through these lattices are Lorentz gases and the corresponding classical dynamics is chaotic. Thus honeycomb lattices are also of interest for understanding eigenstate thermalization and the conductor-insulator transition due to dynamic Anderson localization. PMID- 26871071 TI - Chimera states in bursting neurons. AB - We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global, and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of the stability function in the incoherent (i.e., disorder), coherent, chimera, and multichimera states. Surprisingly, we find that chimera and multichimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is in contrast with the existence of chimera states in populations of nonlocally or globally coupled oscillators. A chemical synaptic coupling function is used which plays a key role in the emergence of chimera states in bursting neurons. The existence of chimera, multichimera, coherent, and disordered states is confirmed by means of the recently introduced statistical measures and mean phase velocity. PMID- 26871072 TI - Infinite hierarchy of nonlinear Schrodinger equations and their solutions. AB - We study the infinite integrable nonlinear Schrodinger equation hierarchy beyond the Lakshmanan-Porsezian-Daniel equation which is a particular (fourth-order) case of the hierarchy. In particular, we present the generalized Lax pair and generalized soliton solutions, plane wave solutions, Akhmediev breathers, Kuznetsov-Ma breathers, periodic solutions, and rogue wave solutions for this infinite-order hierarchy. We find that "even- order" equations in the set affect phase and "stretching factors" in the solutions, while "odd-order" equations affect the velocities. Hence odd-order equation solutions can be real functions, while even-order equation solutions are always complex. PMID- 26871073 TI - Phase oscillators in modular networks: The effect of nonlocal coupling. AB - We study the dynamics of nonlocally coupled phase oscillators in a modular network. The interactions include a phase lag, alpha. Depending on the various parameters the system exhibits a number of different dynamical states. In addition to global synchrony there can also be modular synchrony when each module can synchronize separately to a different frequency. There can also be multicluster frequency chimeras, namely coherent domains consisting of modules that are separately synchronized to different frequencies, coexisting with modules within which the dynamics is desynchronized. We apply the Ott-Antonsen ansatz in order to reduce the effective dimensionality and thereby carry out a detailed analysis of the different dynamical states. PMID- 26871074 TI - Deterministic particle transport in a ratchet flow. AB - This study is motivated by the issue of the pumping of particle through a periodic modulated channel. We focus on a simplified deterministic model of small inertia particles within the Stokes flow framework that we call "ratchet flow." A path-following method is employed in the parameter space in order to retrace the scenario which from bounded periodic solutions leads to particle transport. Depending on whether the magnitude of the particle drag is moderate or large, two main transport mechanisms are identified in which the role of the parity symmetry of the flow differs. For large drag, transport is induced by flow asymmetry, while for moderate drag, since the full transport solution bifurcation structure already exists for symmetric settings, flow asymmetry only makes the transport effective. We analyzed the scenarios of current reversals for each mechanism as well as the role of synchronization. In particular we show that, for large drag, the particle drift is similar to phase slip in a synchronization problem. PMID- 26871075 TI - Chimera patterns under the impact of noise. AB - We investigate two types of chimera states, patterns consisting of coexisting spatially separated domains with coherent and incoherent dynamics, in ring networks of Stuart-Landau oscillators with symmetry-breaking coupling, under the influence of noise. Amplitude chimeras are characterized by temporally periodic dynamics throughout the whole network, but spatially incoherent behavior with respect to the amplitudes in a part of the system; they are long-living transients. Chimera death states generalize chimeras to stationary inhomogeneous patterns (oscillation death), which combine spatially coherent and incoherent domains. We analyze the impact of random perturbations, addressing the question of robustness of chimera states in the presence of white noise. We further consider the effect of symmetries applied to random initial conditions. PMID- 26871076 TI - Correlation functions and correlation widths in quantum-chaotic scattering for mesoscopic systems and nuclei. AB - We derive analytical expressions for the correlation functions of the electronic conductance fluctuations of an open quantum dot under several conditions. Both the variation of energy and that of an external parameter, such as an applied perpendicular or parallel magnetic fields, are considered in the general case of partial openness. These expressions are then used to obtain the ensemble-averaged density of maxima, a measure recently suggested to contain invaluable information concerning the correlation widths of chaotic systems. The correlation width is then calculated for the case of energy variation, and a significant deviation from the Weisskopf estimate is found in the case of two terminals. The results are extended to more than two terminals. All of our results are analytical. The use of these results in other fields, such as nuclei, where the system can only be studied through a variation of the energy, is then discussed. PMID- 26871077 TI - Competition between drift and spatial defects leads to oscillatory and excitable dynamics of dissipative solitons. AB - We have reported in Phys. Rev. Lett. 110, 064103 (2013)PRLTAO0031 900710.1103/PhysRevLett.110.064103 that in systems which otherwise do not show oscillatory dynamics, the interplay between pinning to a defect and pulling by drift allows the system to exhibit excitability and oscillations. Here we build on this work and present a detailed bifurcation analysis of the various dynamical instabilities that result from the competition between a pulling force generated by the drift and a pinning of the solitons to spatial defects. We show that oscillatory and excitable dynamics of dissipative solitons find their origin in multiple codimension-2 bifurcation points. Moreover, we demonstrate that the mechanisms leading to these dynamical regimes are generic for any system admitting dissipative solitons. PMID- 26871078 TI - Experimental and theoretical approach for the clustering of globally coupled density oscillators based on phase response. AB - We investigated the phase-response curve of a coupled system of density oscillators with an analytical approach. The behaviors of two-, three-, and four coupled systems seen in the experiments were reproduced by the model considering the phase-response curve. Especially in a four-coupled system, the clustering state and its incidence rate as functions of the coupling strength are well reproduced with this approach. Moreover, we confirmed that the shape of the phase response curve we obtained analytically was close to that observed in the experiment where a perturbation is added to a single-density oscillator. We expect that this approach to obtaining the phase-response curve is general in the sense that it could be applied to coupled systems of other oscillators such as electrical-circuit oscillators, metronomes, and so on. PMID- 26871079 TI - Generalized Gaussian wave packet dynamics: Integrable and chaotic systems. AB - The ultimate semiclassical wave packet propagation technique is a complex, time dependent Wentzel-Kramers-Brillouin method known as generalized Gaussian wave packet dynamics (GGWPD). It requires overcoming many technical difficulties in order to be carried out fully in practice. In its place roughly twenty years ago, linearized wave packet dynamics was generalized to methods that include sets of off-center, real trajectories for both classically integrable and chaotic dynamical systems that completely capture the dynamical transport. The connections between those methods and GGWPD are developed in a way that enables a far more practical implementation of GGWPD. The generally complex saddle-point trajectories at its foundation are found using a multidimensional Newton-Raphson root search method that begins with the set of off-center, real trajectories. This is possible because there is a one-to-one correspondence. The neighboring trajectories associated with each off-center, real trajectory form a path that crosses a unique saddle; there are exceptions that are straightforward to identify. The method is applied to the kicked rotor to demonstrate the accuracy improvement as a function of h that comes with using the saddle-point trajectories. PMID- 26871080 TI - Breather-to-soliton transitions, nonlinear wave interactions, and modulational instability in a higher-order generalized nonlinear Schrodinger equation. AB - We study the nonlinear waves on constant backgrounds of the higher-order generalized nonlinear Schrodinger (HGNLS) equation describing the propagation of ultrashort optical pulse in optical fibers. We derive the breather, rogue wave, and semirational solutions of the HGNLS equation. Our results show that these three types of solutions can be converted into the nonpulsating soliton solutions. In particular, we present the explicit conditions for the transitions between breathers and solitons with different structures. Further, we investigate the characteristics of the collisions between the soliton and breathers. Especially, based on the semirational solutions of the HGNLS equation, we display the novel interactions between the rogue waves and other nonlinear waves. In addition, we reveal the explicit relation between the transition and the distribution characteristics of the modulation instability growth rate. PMID- 26871081 TI - Hopf bifurcation analysis for a dissipative system with asymmetric interaction: Analytical explanation of a specific property of highway traffic. AB - A dissipative system with asymmetric interaction, the optimal velocity model, shows a Hopf bifurcation concerned with the transition from a homogeneous motion to the formation of a moving cluster, such as the emergence of a traffic jam. We investigate the properties of Hopf bifurcation depending on the particle density, using the dynamical system for the traveling cluster solution of the continuum system derived from the original discrete system of particles. The Hopf bifurcation is revealed as a subcritical one, and the property explains well the specific phenomena in highway traffic: the metastability of jamming transition and the hysteresis effect in the relation of car density and flow rate. PMID- 26871082 TI - Phase-locked scroll waves defy turbulence induced by negative filament tension. AB - Scroll waves in a three-dimensional media may develop into turbulence due to negative tension of the filament. Such negative tension-induced instability of scroll waves has been observed in the Belousov-Zhabotinsky reaction systems. Here we propose a method to restabilize scroll wave turbulence caused by negative tension in three-dimensional chemical excitable media using a circularly polarized (rotating) external field. The stabilization mechanism is analyzed in terms of phase-locking caused by the external field, which makes the effective filament tension positive. The phase-locked scroll waves that have positive tension and higher frequency defy the turbulence and finally restore order. A linear theory for the change of filament tension caused by a generic rotating external field is presented and its predictions closely agree with numerical simulations. PMID- 26871083 TI - Rogue waves for a system of coupled derivative nonlinear Schrodinger equations. AB - Rogue waves (RWs) are unexpectedly strong excitations emerging from an otherwise tranquil background. The nonlinear Schrodinger equation (NLSE), a ubiquitous model with wide applications to fluid mechanics, optics, plasmas, etc., exhibits RWs only in the regime of modulation instability (MI) of the background. For a system of multiple waveguides, the governing coupled NLSEs can produce regimes of MI and RWs, even if each component has dispersion and cubic nonlinearity of opposite signs. A similar effect is demonstrated here for a system of coupled derivative NLSEs (DNLSEs) where the special feature is the nonlinear self steepening of narrow pulses. More precisely, these additional regimes of MI and RWs for coupled DNLSEs depend on the mismatch in group velocities between the components, and the parameters for cubic nonlinearity and self-steepening. RWs considered in this paper differ from those of the NLSEs in terms of the amplification ratio and criteria of existence. Applications to optics and plasma physics are discussed. PMID- 26871084 TI - Chimera states in networks of phase oscillators: The case of two small populations. AB - Chimera states are dynamical patterns in networks of coupled oscillators in which regions of synchronous and asynchronous oscillation coexist. Although these states are typically observed in large ensembles of oscillators and analyzed in the continuum limit, chimeras may also occur in systems with finite (and small) numbers of oscillators. Focusing on networks of 2N phase oscillators that are organized in two groups, we find that chimera states, corresponding to attracting periodic orbits, appear with as few as two oscillators per group and demonstrate that for N>2 the bifurcations that create them are analogous to those observed in the continuum limit. These findings suggest that chimeras, which bear striking similarities to dynamical patterns in nature, are observable and robust in small networks that are relevant to a variety of real-world systems. PMID- 26871085 TI - Discrete breathers for a discrete nonlinear Schrodinger ring coupled to a central site. AB - We examine the existence and properties of certain discrete breathers for a discrete nonlinear Schrodinger model where all but one site are placed in a ring and coupled to the additional central site. The discrete breathers we focus on are stationary solutions mainly localized on one or a few of the ring sites and possibly also the central site. By numerical methods, we trace out and study the continuous families the discrete breathers belong to. Our main result is the discovery of a split bifurcation at a critical value of the coupling between neighboring ring sites. Below this critical value, families form closed loops in a certain parameter space, implying that discrete breathers with and without central-site occupation belong to the same family. Above the split bifurcation the families split up into several separate ones, which bifurcate with solutions with constant ring amplitudes. For symmetry reasons, the families have different properties below the split bifurcation for even and odd numbers of sites. It is also determined under which conditions the discrete breathers are linearly stable. The dynamics of some simpler initial conditions that approximate the discrete breathers are also studied and the parameter regimes where the dynamics remain localized close to the initially excited ring site are related to the linear stability of the exact discrete breathers. PMID- 26871086 TI - Temporal dynamics of connectivity and epidemic properties of growing networks. AB - Traditional mathematical models of epidemic disease had for decades conventionally considered static structure for contacts. Recently, an upsurge of theoretical inquiry has strived towards rendering the models more realistic by incorporating the temporal aspects of networks of contacts, societal and online, that are of interest in the study of epidemics (and other similar diffusion processes). However, temporal dynamics have predominantly focused on link fluctuations and nodal activities, and less attention has been paid to the growth of the underlying network. Many real networks grow: Online networks are evidently in constant growth, and societal networks can grow due to migration flux and reproduction. The effect of network growth on the epidemic properties of networks is hitherto unknown, mainly due to the predominant focus of the network growth literature on the so-called steady state. This paper takes a step towards alleviating this gap. We analytically study the degree dynamics of a given arbitrary network that is subject to growth. We use the theoretical findings to predict the epidemic properties of the network as a function of time. We observe that the introduction of new individuals into the network can enhance or diminish its resilience against endemic outbreaks and investigate how this regime shift depends upon the connectivity of newcomers and on how they establish connections to existing nodes. Throughout, theoretical findings are corroborated with Monte Carlo simulations over synthetic and real networks. The results shed light on the effects of network growth on the future epidemic properties of networks and offers insights for devising a priori immunization strategies. PMID- 26871087 TI - Spontaneous symmetry breaking and phase coexistence in two-color networks. AB - We consider an equilibrium ensemble of large Erdos-Renyi topological random networks with fixed vertex degree and two types of vertices, black and white, prepared randomly with the bond connection probability p. The network energy is a sum of all unicolor triples (either black or white), weighted with chemical potential of triples MU. Minimizing the system energy, we see for some positive MU the formation of two predominantly unicolor clusters, linked by a string of N_{bw} black-white bonds. We have demonstrated that the system exhibits critical behavior manifested in the emergence of a wide plateau on the N_{bw}(MU) curve, which is relevant to a spinodal decomposition in first-order phase transitions. In terms of a string theory, the plateau formation can be interpreted as an entanglement between baby universes in two-dimensional gravity. We conjecture that the observed classical phenomenon can be considered as a toy model for the chiral condensate formation in quantum chromodynamics. PMID- 26871088 TI - Community detection in networks with unequal groups. AB - Recently, a phase transition has been discovered in the network community detection problem below which no algorithm can tell which nodes belong to which communities with success any better than a random guess. This result has, however, so far been limited to the case where the communities have the same size or the same average degree. Here we consider the case where the sizes or average degrees differ. This asymmetry allows us to assign nodes to communities with better-than-random success by examining their local neighborhoods. Using the cavity method, we show that this removes the detectability transition completely for networks with four groups or fewer, while for more than four groups the transition persists up to a critical amount of asymmetry but not beyond. The critical point in the latter case coincides with the point at which local information percolates, causing a global transition from a less-accurate solution to a more-accurate one. PMID- 26871089 TI - Unwinding the hairball graph: Pruning algorithms for weighted complex networks. AB - Empirical networks of weighted dyadic relations often contain "noisy" edges that alter the global characteristics of the network and obfuscate the most important structures therein. Graph pruning is the process of identifying the most significant edges according to a generative null model and extracting the subgraph consisting of those edges. Here, we focus on integer-weighted graphs commonly arising when weights count the occurrences of an "event" relating the nodes. We introduce a simple and intuitive null model related to the configuration model of network generation and derive two significance filters from it: the marginal likelihood filter (MLF) and the global likelihood filter (GLF). The former is a fast algorithm assigning a significance score to each edge based on the marginal distribution of edge weights, whereas the latter is an ensemble approach which takes into account the correlations among edges. We apply these filters to the network of air traffic volume between US airports and recover a geographically faithful representation of the graph. Furthermore, compared with thresholding based on edge weight, we show that our filters extract a larger and significantly sparser giant component. PMID- 26871090 TI - Neural networks with excitatory and inhibitory components: Direct and inverse problems by a mean-field approach. AB - We study the dynamics of networks with inhibitory and excitatory leak-integrate and-fire neurons with short-term synaptic plasticity in the presence of depressive and facilitating mechanisms. The dynamics is analyzed by a heterogeneous mean-field approximation, which allows us to keep track of the effects of structural disorder in the network. We describe the complex behavior of different classes of excitatory and inhibitory components, which give rise to a rich dynamical phase diagram as a function of the fraction of inhibitory neurons. Using the same mean-field approach, we study and solve a global inverse problem: reconstructing the degree probability distributions of the inhibitory and excitatory components and the fraction of inhibitory neurons from the knowledge of the average synaptic activity field. This approach unveils new perspectives on the numerical study of neural network dynamics and the possibility of using these models as a test bed for the analysis of experimental data. PMID- 26871091 TI - Structural inference for uncertain networks. AB - In the study of networked systems such as biological, technological, and social networks the available data are often uncertain. Rather than knowing the structure of a network exactly, we know the connections between nodes only with a certain probability. In this paper we develop methods for the analysis of such uncertain data, focusing particularly on the problem of community detection. We give a principled maximum-likelihood method for inferring community structure and demonstrate how the results can be used to make improved estimates of the true structure of the network. Using computer-generated benchmark networks we demonstrate that our methods are able to reconstruct known communities more accurately than previous approaches based on data thresholding. We also give an example application to the detection of communities in a protein-protein interaction network. PMID- 26871092 TI - Intellectual interchanges in the history of the massive online open-editing encyclopedia, Wikipedia. AB - Wikipedia is a free Internet encyclopedia with an enormous amount of content. This encyclopedia is written by volunteers with various backgrounds in a collective fashion; anyone can access and edit most of the articles. This open editing nature may give us prejudice that Wikipedia is an unstable and unreliable source; yet many studies suggest that Wikipedia is even more accurate and self consistent than traditional encyclopedias. Scholars have attempted to understand such extraordinary credibility, but usually used the number of edits as the unit of time, without consideration of real time. In this work, we probe the formation of such collective intelligence through a systematic analysis using the entire history of 34534110 English Wikipedia articles, between 2001 and 2014. From this massive data set, we observe the universality of both timewise and lengthwise editing scales, which suggests that it is essential to consider the real-time dynamics. By considering real time, we find the existence of distinct growth patterns that are unobserved by utilizing the number of edits as the unit of time. To account for these results, we present a mechanistic model that adopts the article editing dynamics based on both editor-editor and editor-article interactions. The model successfully generates the key properties of real Wikipedia articles such as distinct types of articles for the editing patterns characterized by the interrelationship between the numbers of edits and editors, and the article size. In addition, the model indicates that infrequently referred articles tend to grow faster than frequently referred ones, and articles attracting a high motivation to edit counterintuitively reduce the number of participants. We suggest that this decay of participants eventually brings inequality among the editors, which will become more severe with time. PMID- 26871093 TI - Identifying the direct risk source to contain epidemics more effectively. AB - We investigate the impact of people's perceptions regarding the risk of an epidemic by analyzing the differences between local and global risk perceptions on affecting the epidemic threshold. Three issues are introduced to explain such differences: the indirect risk source, the heterogeneous global risk, and heterogeneity in individuals' intrinsic susceptibilities. When the direct risk source is completely undetected, the local risk perception tends to have no effect on the epidemic threshold, and the effect of the local risk is nearly equivalent to that of the global risk perception, thereby also suggesting a reason why global risk perception cannot affect the epidemic threshold. However, there is a surprising effect of the global risk perception: When its heterogeneity is sufficiently high, an increased epidemic threshold value sometimes may lead to a greater infected ratio. PMID- 26871094 TI - Value of peripheral nodes in controlling multilayer scale-free networks. AB - We analyze the controllability of a two-layer network, where driver nodes can be chosen randomly only from one layer. Each layer contains a scale-free network with directed links and the node dynamics depends on the incoming links from other nodes. We combine the in-degree and out-degree values to assign an importance value w to each node, and distinguish between peripheral nodes with low w and central nodes with high w. Based on numerical simulations, we find that the controllable part of the network is larger when choosing low w nodes to connect the two layers. The control is as efficient when peripheral nodes are driver nodes as it is for the case of more central nodes. However, if we assume a cost to utilize nodes that is proportional to their overall degree, utilizing peripheral nodes to connect the two layers or to act as driver nodes is not only the most cost-efficient solution, it is also the one that performs best in controlling the two-layer network among the different interconnecting strategies we have tested. PMID- 26871095 TI - Models for microtubule cargo transport coupling the Langevin equation to stochastic stepping motor dynamics: Caring about fluctuations. AB - One-dimensional models coupling a Langevin equation for the cargo position to stochastic stepping dynamics for the motors constitute a relevant framework for analyzing multiple-motor microtubule transport. In this work we explore the consistence of these models focusing on the effects of the thermal noise. We study how to define consistent stepping and detachment rates for the motors as functions of the local forces acting on them in such a way that the cargo velocity and run-time match previously specified functions of the external load, which are set on the base of experimental results. We show that due to the influence of the thermal fluctuations this is not a trivial problem, even for the single-motor case. As a solution, we propose a motor stepping dynamics which considers memory on the motor force. This model leads to better results for single-motor transport than the approaches previously considered in the literature. Moreover, it gives a much better prediction for the stall force of the two-motor case, highly compatible with the experimental findings. We also analyze the fast fluctuations of the cargo position and the influence of the viscosity, comparing the proposed model to the standard one, and we show how the differences on the single-motor dynamics propagate to the multiple motor situations. Finally, we find that the one-dimensional character of the models impede an appropriate description of the fast fluctuations of the cargo position at small loads. We show how this problem can be solved by considering two dimensional models. PMID- 26871096 TI - Automated inference procedure for the determination of cell growth parameters. AB - The growth rate and carrying capacity of a cell population are key to the characterization of the population's viability and to the quantification of its responses to perturbations such as drug treatments. Accurate estimation of these parameters necessitates careful analysis. Here, we present a rigorous mathematical approach for the robust analysis of cell count data, in which all the experimental stages of the cell counting process are investigated in detail with the machinery of Bayesian probability theory. We advance a flexible theoretical framework that permits accurate estimates of the growth parameters of cell populations and of the logical correlations between them. Moreover, our approach naturally produces an objective metric of avoidable experimental error, which may be tracked over time in a laboratory to detect instrumentation failures or lapses in protocol. We apply our method to the analysis of cell count data in the context of a logistic growth model by means of a user-friendly computer program that automates this analysis, and present some samples of its output. Finally, we note that a traditional least squares fit can provide misleading estimates of parameter values, because it ignores available information with regard to the way in which the data have actually been collected. PMID- 26871097 TI - Rigidity of transmembrane proteins determines their cluster shape. AB - Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as alpha-helices and beta-sheets have different structural rigidities. We use molecular dynamics simulation of a coarse-grained model of protein-embedded lipid membranes to investigate the mechanisms of protein clustering. For a variety of protein concentrations, our simulations under thermal equilibrium conditions reveal that the structural rigidity of transmembrane domains dramatically affects interactions and changes the shape of the cluster. We have observed stable large aggregates even in the absence of hydrophobic mismatch, which has been previously proposed as the mechanism of protein aggregation. According to our results, semiflexible proteins aggregate to form two-dimensional clusters, while rigid proteins, by contrast, form one dimensional string-like structures. By assuming two probable scenarios for the formation of a two-dimensional triangular structure, we calculate the lipid density around protein clusters and find that the difference in lipid distribution around rigid and semiflexible proteins determines the one- or two dimensional nature of aggregates. It is found that lipids move faster around semiflexible proteins than rigid ones. The aggregation mechanism suggested in this paper can be tested by current state-of-the-art experimental facilities. PMID- 26871098 TI - Analytical catch-slip bond model for arbitrary forces and loading rates. AB - Some biological bonds exhibit a so-called catch regime, where the bond strengthens with increasing load. We build upon recent advances in slip-bond kinetics to develop an analytically tractable, microscopic catch-slip bond model. To facilitate the analysis of force-spectroscopy data, we calculate the bond's mean lifetime and the rupture-force distribution for static loading and linear force ramps. Our results are applicable for arbitrary forces and loading rates, covering the whole range of conditions found in experiments and all-atom simulations. A generalization to account for force transducers of finite stiffness is also provided. PMID- 26871099 TI - Theory of pinned fronts. AB - The properties of a front between two different phases in the presence of a smoothly inhomogeneous external field that takes its critical value at the crossing point is analyzed. Two generic scenarios are studied. In the first, the system admits a bistable solution and the external field governs the rate in which one phase invades the other. The second mechanism corresponds to a continuous transition that, in the case of reactive systems, takes the form of a transcritical bifurcation at the crossing point. We solve for the front shape and for the response of competitive fronts to external noise, showing that static properties and also some of the dynamical features cannot discriminate between the two scenarios. A reliable indicator turns out to be the fluctuation statistics. These take a Gaussian form in the bifurcation case and a double peaked shape in a bistable system. Our results are discussed in the context of biological processes, such as species and communities dynamics in the presence of a resource gradient. PMID- 26871100 TI - Chaperone-assisted translocation of flexible polymers in three dimensions. AB - Polymer translocation through a nanometer-scale pore assisted by chaperones binding to the polymer is a process encountered in vivo for proteins. Studying the relevant models by computer simulations is computationally demanding. Accordingly, previous studies are either for stiff polymers in three dimensions or flexible polymers in two dimensions. Here, we study chaperone-assisted translocation of flexible polymers in three dimensions using Langevin dynamics. We show that differences in binding mechanisms, more specifically, whether a chaperone can bind to a single site or multiple sites on the polymer, lead to substantial differences in translocation dynamics in three dimensions. We show that the single-binding mode leads to dynamics that is very much like that in the constant-force driven translocation and accordingly mainly determined by tension propagation on the cis side. We obtain beta~1.26 for the exponent for the scaling of the translocation time with polymer length. This fairly low value can be explained by the additional friction due to binding particles. The multiple-site binding leads to translocation the dynamics of which is mainly determined by the trans side. For this process we obtain beta~1.36. This value can be explained by our derivation of beta=4/3 for constant-bias translocation, where translocated polymer segments form a globule on the trans side. Our results pave the way for understanding and utilizing chaperone-assisted translocation where variations in microscopic details lead to rich variations in the emerging dynamics. PMID- 26871101 TI - Elastic regimes of subisostatic athermal fiber networks. AB - Athermal models of disordered fibrous networks are highly useful for studying the mechanics of elastic networks composed of stiff biopolymers. The underlying network architecture is a key aspect that can affect the elastic properties of these systems, which include rich linear and nonlinear elasticity. Existing computational approaches have focused on both lattice-based and off-lattice networks obtained from the random placement of rods. It is not obvious, a priori, whether the two architectures have fundamentally similar or different mechanics. If they are different, it is not clear which of these represents a better model for biological networks. Here, we show that both approaches are essentially equivalent for the same network connectivity, provided the networks are subisostatic with respect to central force interactions. Moreover, for a given subisostatic connectivity, we even find that lattice-based networks in both two and three dimensions exhibit nearly identical nonlinear elastic response. We provide a description of the linear mechanics for both architectures in terms of a scaling function. We also show that the nonlinear regime is dominated by fiber bending and that stiffening originates from the stabilization of subisostatic networks by stress. We propose a generalized relation for this regime in terms of the self-generated normal stresses that develop under deformation. Different network architectures have different susceptibilities to the normal stress but essentially exhibit the same nonlinear mechanics. Such a stiffening mechanism has been shown to successfully capture the nonlinear mechanics of collagen networks. PMID- 26871102 TI - Individuality and universality in the growth-division laws of single E. coli cells. AB - The mean size of exponentially dividing Escherichia coli cells in different nutrient conditions is known to depend on the mean growth rate only. However, the joint fluctuations relating cell size, doubling time, and individual growth rate are only starting to be characterized. Recent studies in bacteria reported a universal trend where the spread in both size and doubling times is a linear function of the population means of these variables. Here we combine experiments and theory and use scaling concepts to elucidate the constraints posed by the second observation on the division control mechanism and on the joint fluctuations of sizes and doubling times. We found that scaling relations based on the means collapse both size and doubling-time distributions across different conditions and explain how the shape of their joint fluctuations deviates from the means. Our data on these joint fluctuations highlight the importance of cell individuality: Single cells do not follow the dependence observed for the means between size and either growth rate or inverse doubling time. Our calculations show that these results emerge from a broad class of division control mechanisms requiring a certain scaling form of the "division hazard rate function," which defines the probability rate of dividing as a function of measurable parameters. This "model free" approach gives a rationale for the universal body-size distributions observed in microbial ecosystems across many microbial species, presumably dividing with multiple mechanisms. Additionally, our experiments show a crossover between fast and slow growth in the relation between individual-cell growth rate and division time, which can be understood in terms of different regimes of genome replication control. PMID- 26871103 TI - Swing motion as a diffusion mechanism of lipid bilayers in a gel phase. AB - Lipid bilayers are a model system for studying the properties of cell membranes. For lipid bilayers of a single lipid component, there is a phase transition from a fluid phase to a gel phase as the temperature is decreased. The dynamic behavior of lipids in the gel phase is interesting: some models show dynamic heterogeneity with a large disparity in timescales between fast and slow molecules, and a spatial segregation of the slow molecules. In this paper we study the dynamics of coarse-grained models of lipid bilayers using the dry Martini, Lennard-Jones Martini, polarizable Martini, and BMW models. All four models show similar dynamical behaviors in the gel phase although the transition temperature is model-dependent. We find that the primary mode of transport in the gel phase is a hopping of the lipid molecules. Hopping is seen in both the translational and rotational dynamics, which are correlated, i.e., the lipid molecules display a swing-like motion in the gel phase. PMID- 26871104 TI - Single-molecule force measurements of the polymerizing dimeric subunit of von Willebrand factor. AB - Von Willebrand factor (VWF) multimers are large adhesive proteins that are essential to the initiation of hemostatic plugs at sites of vascular injury. The binding of VWF multimers to platelets, as well as VWF proteolysis, is regulated by shear stresses that alter VWF multimeric conformation. We used single molecule manipulation with atomic force microscopy (AFM) to investigate the effect of high fluid shear stress on soluble dimeric and multimeric forms of VWF. VWF dimers are the smallest unit that polymerizes to construct large VWF multimers. The resistance to mechanical unfolding with or without exposure to shear stress was used to evaluate VWF conformational forms. Our data indicate that, unlike recombinant VWF multimers (RVWF), recombinant dimeric VWF (RDVWF) unfolding force is not altered by high shear stress (100dynes/cm^{2} for 3 min at 37^{?}C). We conclude that under the shear conditions used (100dynes/cm^{2} for 3 min at 37^{?}C), VWF dimers do not self-associate into a conformation analogous to that attained by sheared large VWF multimers. PMID- 26871105 TI - Inducing rostrum interfacial waves by fluid-solid coupling in a Chinese river dolphin (Lipotesvexillifer). AB - Through numerically solving the appropriate wave equations, propagation of biosonar signals in a Chinese river dolphin (baiji) was studied. The interfacial waves along the rostrum-tissue interfaces, including both compressional (longitudinal) and shear (transverse) waves in the solid rostrum through fluid solid coupling were examined. The baiji's rostrum was found to effect acoustic beam formation not only as an interfacial wave generator but also as a sound reflector. The wave propagation patterns in the solid rostrum were found to significantly change the wave movement through the bone. Vibrations in the rostrum, expressed in solid displacement, initially increased but eventually decreased from posterior to anterior sides, indicating a complex physical process. Furthermore, the comparisons among seven cases, including the combination of (1) the rostrum, melon, and air sacs; (2) rostrum-air sacs; (3) rostrum-melon; (4) only rostrum; (5) air sacs-melon; (6) only air sacs; and (7) only melon revealed that the cases including the rostrum were better able to approach the complete system by inducing rostrum-tissue interfacial waves and reducing the differences in main beam angle and -3 dB beam width. The interfacial waves in the rostrum were considered complementary with reflection to determine the obbligato role of the rostrum in the baiji's biosonar emission. The far-field beams formed from complete fluid-solid models and non-fluid-solid models were compared to reveal the effects brought by the consideration of shear waves of the solid structures of the baiji. The results may provide useful information for further understanding the role of the rostrum in this odontocete species. PMID- 26871106 TI - Wavelength selection of rippling patterns in myxobacteria. AB - Rippling patterns of myxobacteria appear in starving colonies before they aggregate to form fruiting bodies. These periodic traveling cell density waves arise from the coordination of individual cell reversals, resulting from an internal clock regulating them and from contact signaling during bacterial collisions. Here we revisit a mathematical model of rippling in myxobacteria due to Igoshin et al. [Proc. Natl. Acad. Sci. USA 98, 14913 (2001)PNASA60027 842410.1073/pnas.221579598 and Phys. Rev. E 70, 041911 (2004)PLEEE81539 375510.1103/PhysRevE.70.041911]. Bacteria in this model are phase oscillators with an extra internal phase through which they are coupled to a mean field of oppositely moving bacteria. Previously, patterns for this model were obtained only by numerical methods, and it was not possible to find their wave number analytically. We derive an evolution equation for the reversal point density that selects the pattern wave number in the weak signaling limit, shows the validity of the selection rule by solving numerically the model equations, and describes other stable patterns in the strong signaling limit. The nonlocal mean-field coupling tends to decohere and confine patterns. Under appropriate circumstances, it can annihilate the patterns leaving a constant density state via a nonequilibrium phase transition reminiscent of destruction of synchronization in the Kuramoto model. PMID- 26871107 TI - Membrane tubulation from giant lipid vesicles in alternating electric fields. AB - We report on the formation of tubular membrane protrusions from giant unilamellar vesicles in alternating electric fields. The construction of the experimental chamber permitted the application of external AC fields with strength of dozens of V/mm and kHz frequency during relatively long time periods (several minutes). Besides the vesicle electrodeformation from quasispherical to prolate ellipsoidal shape, the formation of long tubular membrane protrusions with length of up to several vesicle diameters, arising from the vesicular surface in the field direction, was registered and analyzed. The threshold electric field at which the electro-induced protrusions appeared was lower than the field strengths inducing membrane electroporation. PMID- 26871108 TI - Cell-substrate impedance fluctuations of single amoeboid cells encode cell-shape and adhesion dynamics. AB - We show systematic electrical impedance measurements of single motile cells on microelectrodes. Wild-type cells and mutant strains were studied that differ in their cell-substrate adhesion strength. We recorded the projected cell area by time-lapse microscopy and observed irregular oscillations of the cell shape. These oscillations were correlated with long-term variations in the impedance signal. Superposed to these long-term trends, we observed fluctuations in the impedance signal. Their magnitude clearly correlated with the adhesion strength, suggesting that strongly adherent cells display more dynamic cell-substrate interactions. PMID- 26871109 TI - Transient amplification limits noise suppression in biochemical networks. AB - Cell physiology is orchestrated, on a molecular level, through complex networks of biochemical reactions. The propagation of random fluctuations through these networks can significantly impact cell behavior, raising challenging questions about how network design shapes the cell's ability to suppress or exploit these fluctuations. Here, drawing on insights from statistical physics, fluid dynamics, and systems biology, we explore how transient amplification phenomena arising from network connectivity naturally limit a biochemical system's ability to suppress small fluctuations around steady-state behaviors. We find that even a simple system consisting of two variables linked by a single interaction is capable of amplifying small fluctuations orders of magnitude beyond the levels predicted by linear stability theory. We also find that adding additional interactions can promote further amplification, even when these interactions implement classic design strategies known to suppress fluctuations. These results establish that transient amplification is an essential factor determining baseline noise levels in stable intracellular networks. Significantly, our analysis is not bound to specific systems or interaction mechanisms: we find that noise amplification is an emergent phenomenon found near steady states in any network containing sufficiently strong interactions, regardless of its form or function. PMID- 26871110 TI - Closed-loop feedback control and bifurcation analysis of epileptiform activity via optogenetic stimulation in a mathematical model of human cortex. AB - Optogenetics provides a method of neuron stimulation that has high spatial, temporal, and cell-type specificity. Here we present a model of optogenetic feedback control that targets the inhibitory population, which expresses light sensitive channelrhodopsin-2 channels, in a mean-field model of undifferentiated cortex that is driven to seizures. The inhibitory population is illuminated with an intensity that is a function of electrode measurements obtained via the cortical model. We test the efficacy of this control method on seizurelike activity observed in two parameter spaces of the cortical model that most closely correspond to seizures observed in patients. We also compare the effect of closed loop and open-loop control on seizurelike activity using a less-complicated ordinary differential equation model of the undifferentiated cortex in parameter space. Seizurelike activity is successfully suppressed in both parameter planes using optimal illumination intensities less likely to have adverse effects on cortical tissue. PMID- 26871111 TI - Nonuniform elastic properties of macromolecules and effect of prestrain on their continuum nature. AB - Many experimental and theoretical methods have been developed to calculate the coarse-grained continuum elastic properties of macromolecules. However, all of those methods assume uniform elastic properties. Following the continuum mechanics framework, we present a systematic way of calculating the nonuniform effective elastic properties from atomic thermal fluctuations obtained from molecular dynamics simulation at any coarse-grained scale using a potential of the mean-force approach. We present the results for a mutant of Sesbania mosaic virus capsid, where we calculate the elastic moduli at different scales and observe an apparent problem with the chosen reference configuration in some cases. We present a possible explanation using an elastic network model, where inducing random prestrain results in a similar behavior. This phenomenon provides a novel insight into the continuum nature of macromolecules and defines the limits on details that the elasticity theory can capture. Further investigation into prestrains could elucidate important aspects of conformational dynamics of macromolecules. PMID- 26871112 TI - Determination of linear viscoelastic properties of an entangled polymer melt by probe rheology simulations. AB - Particle rheology is used to extract the linear viscoelastic properties of an entangled polymer melt from molecular dynamics simulations. The motion of a stiff, approximately spherical particle is tracked in both passive and active modes. We demonstrate that the dynamic modulus of the melt can be extracted under certain limitations using this technique. As shown before for unentangled chains [Karim et al., Phys. Rev. E 86, 051501 (2012)PLEEE81539 375510.1103/PhysRevE.86.051501], the frequency range of applicability is substantially expanded when both particle and medium inertia are properly accounted for by using our inertial version of the generalized Stokes-Einstein relation (IGSER). The system used here introduces an entanglement length d_{T}, in addition to those length scales already relevant: monomer bead size d, probe size R, polymer radius of gyration R_{g}, simulation box size L, shear wave penetration length Delta, and wave period Lambda. Previously, we demonstrated a number of restrictions necessary to obtain the relevant fluid properties: continuum approximation breaks down when d?Lambda; medium inertia is important and IGSER is required when R?Lambda; and the probe should not experience hydrodynamic interaction with its periodic images, L?Delta. These restrictions are also observed here. A simple scaling argument for entangled polymers shows that the simulation box size must scale with polymer molecular weight as M_{w}^{3}. Continuum analysis requires the existence of an added mass to the probe particle from the entrained medium but was not observed in the earlier work for unentangled chains. We confirm here that this added mass is necessary only when the thickness L_{S} of the shell around the particle that contains the added mass, L_{S}>d. We also demonstrate that the IGSER can be used to predict particle displacement over a given timescale from knowledge of medium viscoelasticity; such ability will be of interest for designing nanoparticle-based drug delivery. PMID- 26871113 TI - Nature of the collapse transition in interacting self-avoiding trails. AB - We study the interacting self-avoiding trail (ISAT) model on a Bethe lattice of general coordination q and on a Husimi lattice built with squares and coordination q=4. The exact grand-canonical solutions of the model are obtained, considering that up to K monomers can be placed on a site and associating a weight omega_{i} with an i-fold visited site. Very rich phase diagrams are found with nonpolymerized, regular polymerized, and dense polymerized phases separated by lines (or surfaces) of continuous and discontinuous transitions. For a Bethe lattice with q=4 and K=2, the collapse transition is identified with a bicritical point and the collapsed phase is associated with the dense polymerized (solidlike) phase instead of the regular polymerized (liquidlike) phase. A similar result is found for the Husimi lattice, which may explain the difference between the collapse transition for ISATs and for interacting self-avoiding walks on the square lattice. For q=6 and K=3 (studied on the Bethe lattice only), a more complex phase diagram is found, with two critical planes and two coexistence surfaces, separated by two tricritical and two critical end-point lines meeting at a multicritical point. The mapping of the phase diagrams in the canonical ensemble is discussed and compared with simulational results for regular lattices. PMID- 26871114 TI - Shell formation in short like-charged polyelectrolytes in a harmonic trap. AB - Inspired by recent experiments and simulations on pattern formation in biomolecules by optical tweezers, a theoretical description based on the reference interaction site model (RISM) is developed to calculate the equilibrium density profiles of small polyelectrolytes in an external potential. The formalism is applied to the specific case of a finite number of Gaussian and rodlike polyelectrolytes trapped in a harmonic potential. The density profiles of the polyelectrolytes are studied over a range of lengths and numbers of polyelectrolytes in the trap, and the strength of the trap potential. For smaller polymers we recover the results for point charges. In the mean field limit the longer polymers, unlike point charges, form a shell at the boundary layer. When the interpolymer correlations are included, the density profiles of the polymers show sharp shells even at weaker trap strengths. The implications of these results are discussed. PMID- 26871115 TI - Strong-coupling electrostatic theory of polymer counterions close to planar charges. AB - Strong-coupling phenomena, such as like-charge macroion attraction, opposite charged macroion repulsion, charge renormalization, and charge inversion, are known to be mediated by multivalent counterions. Most theories treat the counterions as point charges and describe the system by a single coupling parameter that measures the strength of the Coulomb interactions. In many biological systems, the counterions are highly charged and have finite sizes and can be well-described by polyelectrolytes. The shapes and orientations of these polymer counterions play a major role in the thermodynamics of these systems. In this work we apply a field-theoretic description in the strong-coupling regime to the polymer counterions in the presence of a fixed charge distribution. We work out the special cases of rodlike polymer counterions confined by one, and two charged walls, respectively. The effects of the geometry of the rodlike counterions and the excluded volume of the walls on the density, pressure, and free energy of the rodlike counterions are discussed. PMID- 26871116 TI - Poisson-Boltzmann thermodynamics of counterions confined by curved hard walls. AB - We consider a set of identical mobile pointlike charges (counterions) confined to a domain with curved hard walls carrying a uniform fixed surface charge density, the system as a whole being electroneutral. Three domain geometries are considered: a pair of parallel plates, the cylinder, and the sphere. The particle system in thermal equilibrium is assumed to be described by the nonlinear Poisson Boltzmann theory. While the effectively one-dimensional plates and the two dimensional cylinder have already been solved, the three-dimensional sphere problem is not integrable. It is shown that the contact density of particles at the charged surface is determined by a first-order Abel differential equation of the second kind which is a counterpart of Enig's equation in the critical theory of gravitation and combustion or explosion. This equation enables us to construct the exact series solutions of the contact density in the regions of small and large surface charge densities. The formalism provides, within the mean-field Poisson-Boltzmann framework, the complete thermodynamics of counterions inside a charged sphere (salt-free system). PMID- 26871117 TI - Analysis of spatial correlations in a model two-dimensional liquid through eigenvalues and eigenvectors of atomic-level stress matrices. AB - Considerations of local atomic-level stresses associated with each atom represent a particular approach to address structures of disordered materials at the atomic level. We studied structural correlations in a two-dimensional model liquid using molecular dynamics simulations in the following way. We diagonalized the atomic level stress tensor of every atom and investigated correlations between the eigenvalues and orientations of the eigenvectors of different atoms as a function of distance between them. It is demonstrated that the suggested approach can be used to characterize structural correlations in disordered materials. In particular, we found that changes in the stress correlation functions on decrease of temperature are the most pronounced for the pairs of atoms with separation distance that corresponds to the first minimum in the pair density function. We also show that the angular dependencies of the stress correlation functions previously reported by Wu et al. [Phys. Rev. E 91, 032301 (2015)10.1103/PhysRevE.91.032301] do not represent the anisotropic Eshelby's stress fields, as it is suggested, but originate in the rotational properties of the stress tensors. PMID- 26871118 TI - Theory for the dynamics of dense systems of athermal self-propelled particles. AB - We present a derivation of a recently proposed theory for the time dependence of density fluctuations in stationary states of strongly interacting, athermal, self propelled particles. The derivation consists of two steps. First, we start from the equation of motion for the joint distribution of particles' positions and self-propulsions and we integrate out the self-propulsions. In this way we derive an approximate, many-particle evolution equation for the probability distribution of the particles' positions. Second, we use this evolution equation to describe the time dependence of steady-state density correlations. We derive a memory function representation of the density correlation function and then we use a factorization approximation to obtain an approximate expression for the memory function. In the final equation of motion for the density correlation function the nonequilibrium character of the active system manifests itself through the presence of a new steady-state correlation function that quantifies spatial correlations of the velocities of the particles. This correlation function enters into the frequency term, and thus it describes the dependence of the short-time dynamics on the properties of the self-propulsions. More importantly, the correlation function of particles' velocities enters into the vertex of the memory function and through the vertex it modifies the long-time glassy dynamics. PMID- 26871119 TI - Two-scale evolution during shear reversal in dense suspensions. AB - We use shear-reversal simulations to explore the rheology of dense, non-Brownian, noninertial, suspensions, resolving lubrication forces between neighboring particles and modeling particle surface contacts. The transient stress response to an abrupt reversal of the direction of shear shows rate-independent, nonmonotonic behavior, capturing the salient features of the corresponding classical experiments. Based on analyses of the hydrodynamic and particle contact stresses and related contact networks, we demonstrate distinct responses at small and large strains, associated with contact breakage and structural reorientation, respectively, emphasizing the importance of particle contacts. Consequently, the hydrodynamic and contact stresses evolve over disparate strain scales and with opposite trends, resulting in nonmonotonic behavior when combined. We further elucidate the roles of particle roughness and repulsion in determining the microstructure and hence the stress response at each scale. PMID- 26871120 TI - Charge reversal at a planar boundary between two dielectrics. AB - Despite the ubiquitous character and relevance of the electric double layer in the entire realm of interface and colloid science, very little is known of the effect that surface heterogeneity exerts on the underlying mechanisms of ion adsorption. Herein, computer simulations offer a perspective that, in sharp contrast to the homogeneously charged surface, discrete groups promote multivalent counterion binding, leading to charge reversal but possibly having not a sign change of the electrophoretic mobility. Counterintuitively, the introduction of dielectric images yields a significantly greater accumulation of counterions, which further facilitates the magnitude of charge reversal. The reported results are very sensitive to both the degree of ion hydration and the representation of surface charges. Our findings shed light on the mechanism for charge reversal over a broad range of coupling regimes operating the adsorption of counterions through surface group bridging attraction with their own images and provide opportunities for experimental studies and theoretical development. PMID- 26871121 TI - Nonholonomic diffusion of a stochastic sled. AB - A sled is a stylized mechanical model of a system which is constrained to move in space in a specific orientation, i.e., in the direction of the runners of the sled or a blade. The negation of motion transverse to the runners renders the sled a nonholonomic mechanical system. In this paper we report on the unexpected and fascinating richness of the dynamics of such a sled if it is subject to random forces. Specifically we show that the ensuing random dynamics is characterized by relatively smooth sections of motion interspersed by episodes of persistent tumbling (change of orientation) and sharp reversals resembling the random walks of bacterial cells. In the presence of self-propulsion, the diffusivity of the sled can be enhanced and suppressed depending on the directionality and strength of the propulsive force. PMID- 26871123 TI - Colloidal particles driven across periodic optical-potential-energy landscapes. AB - We study the motion of colloidal particles driven by a constant force over a periodic optical potential energy landscape. First, the average particle velocity is found as a function of the driving velocity and the wavelength of the optical potential energy landscape. The relationship between average particle velocity and driving velocity is found to be well described by a theoretical model treating the landscape as sinusoidal, but only at small trap spacings. At larger trap spacings, a nonsinusoidal model for the landscape must be used. Subsequently, the critical velocity required for a particle to move across the landscape is determined as a function of the wavelength of the landscape. Finally, the velocity of a particle driven at a velocity far exceeding the critical driving velocity is examined. Both of these results are again well described by the two theoretical routes for small and large trap spacings, respectively. Brownian motion is found to have a significant effect on the critical driving velocity but a negligible effect when the driving velocity is high. PMID- 26871122 TI - Improved efficiency of heat generation in nonlinear dynamics of magnetic nanoparticles. AB - The deterministic Landau-Lifshitz-Gilbert equation has been used to investigate the nonlinear dynamics of magnetization and the specific loss power in magnetic nanoparticles with uniaxial anisotropy driven by a rotating magnetic field. We propose a new type of applied field, which is "simultaneously rotating and alternating," i.e., the direction of the rotating external field changes periodically. We show that a more efficient heat generation by magnetic nanoparticles is possible with this new type of applied field and we suggest its possible experimental realization in cancer therapy which requires the enhancement of loss energies. PMID- 26871124 TI - Quantitative approximation schemes for glasses. AB - By means of a systematic expansion around the infinite-dimensional solution, we obtain an approximation scheme to compute properties of glasses in low dimensions. The resulting equations take as input the thermodynamic and structural properties of the equilibrium liquid, and from this they allow one to compute properties of the glass. They are therefore similar in spirit to the Mode Coupling approximation scheme. Our scheme becomes exact, by construction, in dimension d->infinity, and it can be improved systematically by adding more terms in the expansion. PMID- 26871125 TI - Gelation in mixtures of polymers and bidisperse colloids. AB - We investigated the effects of varying the volume fraction of large particles (r) on the linear rheology and microstructure of mixtures of polymers and bidisperse colloids, in which the ratio of the small and large particle diameters was alpha=0.31 or alpha=0.45. Suspensions formulated at a total volume fraction of phi_{T}=0.15 and a constant concentration of polymer in the free volume c/c^{*}~0.7 contained solid-like gels for small r and fluids or fluids of clusters at large r. The solid-like rheology and microstructure of these suspensions changed little with r when r was small, and fluidized only when r>0.8. By contrast, dense suspensions with phi_{T}=0.40 and alpha=0.31 contained solid-like gels at all concentrations of large particles and exhibited only modest rheological and microstructural changes upon varying the volume fraction of large particles. These results suggest that the effect of particle-size dispersity on the properties of colloid-polymer mixtures are asymmetric in particle size and are most pronounced near a gelation boundary. PMID- 26871127 TI - Long-lived anomalous thermal diffusion induced by elastic cell membranes on nearby particles. AB - The physical approach of a small particle (virus, medical drug) to the cell membrane represents the crucial first step before active internalization and is governed by thermal diffusion. Using a fully analytical theory we show that the stretching and bending of the elastic membrane by the approaching particle induces a memory in the system, which leads to anomalous diffusion, even though the particle is immersed in a purely Newtonian liquid. For typical cell membranes the transient subdiffusive regime extends beyond 10 ms and can enhance residence times and possibly binding rates up to 50%. Our analytical predictions are validated by numerical simulations. PMID- 26871126 TI - Self-propulsion and interactions of catalytic particles in a chemically active medium. AB - Enzymatic "machines," such as catalytic rods or colloids, can self-propel and interact by generating gradients of their substrates. We theoretically investigate the behaviors of such machines in a chemically active environment where their catalytic substrates are continuously synthesized and destroyed, as occurs in living cells. We show how the kinetic properties of the medium modulate self-propulsion and pairwise interactions between machines, with the latter controlled by a tunable characteristic interaction range analogous to the Debye screening length in an electrolytic solution. Finally, we discuss the effective force arising between interacting machines and possible biological applications, such as partitioning of bacterial plasmids. PMID- 26871129 TI - Nematic liquid crystals in a spatially step-wise magnetic field. AB - We study the molecular reorientation induced by a textured external field in a nematic liquid crystal (nLC). In particular, we consider an infinitely wide cell with strong planar anchoring boundary conditions, subjected to a spatially periodic piecewise magnetic field. In the framework of the Frank's continuum theory, we use the perturbation analysis to study in detail the field-induced splay-bend Freedericksz transition. A numerical approach, based on the finite differences method, is instead employed to solve the fully nonlinear equations. At high field strengths, an analytic approach allows us to draw the bulk profile of the director in terms of elliptic integrals. Finally, through the application of the Bruggeman texture hydrodynamics theory, we qualitatively discuss on the LCs piecewise director configuration under sliding interfaces, which can be adopted to actively regulate friction. Our study opens the pathway for the application of highly controlled nLC texturing for tribotronics. PMID- 26871128 TI - Influence of molecular-weight polydispersity on the glass transition of polymers. AB - It is well known that the polymer glass transition temperature T_{g} is dependent on molecular weight, but the role of molecular-weight polydispersity on T_{g} is unclear. Using molecular-dynamics simulations, we clarify that for polymers with the same number-average molecular weight, the molecular-weight distribution profile (either in Schulz-Zimm form or in bimodal form) has very little influence on the glass transition temperature T_{g}, the average segment dynamics (monomer motion, bond orientation relaxation, and torsion transition), and the relaxation time spectrum, which are related to the local nature of the glass transition. By analyzing monomer motions in different chains, we find that the motion distribution of monomers is altered by molecular-weight polydispersity. Molecular weight polydispersity dramatically enhances the dynamic heterogeneity of monomer diffusive motions after breaking out of the "cage," but it has a weak influence on the dynamic heterogeneity of the short time scales and the transient spatial correlation between temporarily localized monomers. The stringlike cooperative motion is also not influenced by molecular-weight polydispersity, supporting the idea that stringlike collective motion is not strongly correlated with chain connectivity. PMID- 26871130 TI - Electric-field-induced weakly chaotic transients in ferroelectric liquid crystals. AB - Nonlinear dynamics induced in surface stabilized ferroelectric liquid crystals by strong alternating external electric fields is studied both theoretically and experimentally. As has already been shown, molecular reorientations induced by sufficiently strong fields of high-enough frequencies can reveal a long transient behavior that has a weakly chaotic character. The resulting complex dynamics of ferroelectric liquid crystals can be considered not only as a consequence of irregular motions of particular molecules but also as a repercussion of a surface enforced partial decorrelation of nonlinear molecular motions within smectic layers. To achieve more insight into the nature of this phenomenon and to show that the underlying complex field-induced behavior of smectic liquid crystals is not exceptional, ranges of system parameters for which the chaotic behavior occurs are determined. It is proved that there exists a large enough set of initial phase trajectory points, for which weakly chaotic long-time transitory phenomena occur, and, thereby, it is demonstrated that such a chaotic behavior can be regarded as being typical for strongly field-driven thin liquid crystal systems. Additionally, the influence of low-amplitude random noise on the duration of the transient processes is numerically studied. The strongly nonlinear contribution to the electro-optic response, experimentally determined for liquid crystal samples at frequencies lower than the actual field frequency, is also analyzed for long-time signal sequences. Using a statistical approach to distinguish numerically response signals of samples from noise generated by measuring devices, it is shown that the distribution of sample signals distinctly differs from the device noise. This evidently corroborates the occurrence of the nonlinear low-frequency effect, found earlier for different surface stabilized liquid crystal samples. PMID- 26871131 TI - Tunable topological valence in nematic shells on spherocylindrical colloidal particles. AB - We perform molecular dynamics simulations of the orientational ordering on nematic shells delimited by spherocylindrical nanoscopic colloidal particles. We show that under conditions of degenerate planar anchoring, the equilibrium director field structure in these shells exhibits pairs of +1/2 topological defects at the poles of spherical cups in the absence of an external electric field. In addition, a certain number of pairs of +/-1/2 defects occurs on the spherical cups far from the poles, thus resulting in a total of eight valence spots. A strong field applied along the main spherocylindrical axis removes the +/-1/2 defect pairs while it coalesces the polar ones into a single +1 topological defect. A strong transverse field destroys all defects on the spherical cups but generates four +1/2 defects in the cylindrical part. Therefore, an external field can be used to control the number of valence centers in spherocylindrical nematic shells, thus unveiling their capability of acting as multivalent building blocks for nanophotonic devices. PMID- 26871132 TI - Phases and structures of sunset yellow and disodium cromoglycate mixtures in water. AB - We study phases and structures of mixtures of two representative chromonic liquid crystal materials, sunset yellow FCF (SSY) and disodium cromoglycate (DSCG), in water. A variety of combinations of isotropic, nematic (N), and columnar (also called M) phases are observed depending on their concentrations, and a phase diagram is made. We find a tendency for DSCG-rich regions to show higher-order phases while SSY-rich regions show lower-order ones. We observe uniform mesophases only when one of the materials is sparse in the N phases. Their miscibility in M phases is so low that essentially complete phase separation occurs. X-ray scattering and spectroscopy studies confirm that SSY and DSCG molecules do not mix when they form chromonic aggregates and neither do their aggregates when they form M phases. PMID- 26871133 TI - Analytical description of the Saturn-ring defect in nematic colloids. AB - We derive an analytical formula for the Saturn-ring configuration around a small colloidal particle suspended in nematic liquid crystal. In particular we obtain an explicit expression for the ring radius and its dependence on the anchoring energy. We work within Landau-de Gennes theory: Nematic alignment is described by a tensorial order parameter. For nematic colloids this model had previously been used exclusively to perform numerical computations. Our method demonstrates that the tensorial theory can also be used to obtain analytical results, suggesting a different approach to the understanding of nematic colloidal interactions. PMID- 26871134 TI - Experimental realization of an incompressible Newtonian fluid in two dimensions. AB - The Brownian diffusion of micron-scale inclusions in freely suspended smectic-A liquid crystal films a few nanometers thick and several millimeters in diameter depends strongly on the air surrounding the film. Near atmospheric pressure, the three-dimensionally coupled film-gas system is well described by Hughes Pailthorpe-White hydrodynamic theory but at lower pressure (p?70 torr), the diffusion coefficient increases substantially, tending in high vacuum toward the two-dimensional limit where it is determined by film size. In the absence of air, the films are found to be a nearly ideal physical realization of a two dimensional, incompressible Newtonian fluid. PMID- 26871135 TI - Width and extremal height distributions of fluctuating interfaces with window boundary conditions. AB - We present a detailed study of squared local roughness (SLRDs) and local extremal height distributions (LEHDs), calculated in windows of lateral size l, for interfaces in several universality classes, in substrate dimensions d_{s}=1 and 2. We show that their cumulants follow a Family-Vicsek-type scaling, and, at early times, when xi?l (xi is the correlation length), the rescaled SLRDs are given by log-normal distributions, with their nth cumulant scaling as (xi/l)^{(n 1)d_{s}}. This gives rise to an interesting temporal scaling for such cumulants as _{c}~t^{gamma_{n}}, with gamma_{n}=2nbeta+(n-1)d_{s}/z=[2n+(n 1)d_{s}/alpha]beta. This scaling is analytically proved for the Edwards-Wilkinson (EW) and random deposition interfaces and numerically confirmed for other classes. In general, it is featured by small corrections, and, thus, it yields exponents gamma_{n} (and, consequently, alpha,beta and z) in good agreement with their respective universality class. Thus, it is a useful framework for numerical and experimental investigations, where it is usually hard to estimate the dynamic z and mainly the (global) roughness alpha exponents. The stationary (for xi?l) SLRDs and LEHDs of the Kardar-Parisi-Zhang (KPZ) class are also investigated, and, for some models, strong finite-size corrections are found. However, we demonstrate that good evidence of their universality can be obtained through successive extrapolations of their cumulant ratios for long times and large l. We also show that SLRDs and LEHDs are the same for flat and curved KPZ interfaces. PMID- 26871136 TI - Variational formulation and numerical accuracy of a quantitative phase-field model for binary alloy solidification with two-sided diffusion. AB - We present the variational formulation of a quantitative phase-field model for isothermal low-speed solidification in a binary dilute alloy with diffusion in the solid. In the present formulation, cross-coupling terms between the phase field and composition field, including the so-called antitrapping current, naturally arise in the time evolution equations. One of the essential ingredients in the present formulation is the utilization of tensor diffusivity instead of scalar diffusivity. In an asymptotic analysis, it is shown that the correct mapping between the present variational model and a free-boundary problem for alloy solidification with an arbitrary value of solid diffusivity is successfully achieved in the thin-interface limit due to the cross-coupling terms and tensor diffusivity. Furthermore, we investigate the numerical performance of the variational model and also its nonvariational versions by carrying out two dimensional simulations of free dendritic growth. The nonvariational model with tensor diffusivity shows excellent convergence of results with respect to the interface thickness. PMID- 26871137 TI - Protocol dependence of the jamming transition. AB - We propose a theoretical framework for predicting the protocol dependence of the jamming transition for frictionless spherical particles that interact via repulsive contact forces. We study isostatic jammed disk packings obtained via two protocols: isotropic compression and simple shear. We show that for frictionless systems, all jammed packings can be obtained via either protocol. However, the probability to obtain a particular jammed packing depends on the packing-generation protocol. We predict the average shear strain required to jam initially unjammed isotropically compressed packings from the density of jammed packings, shape of their basins of attraction, and path traversed in configuration space. We compare our predictions to simulations of shear strain induced jamming and find quantitative agreement. We also show that the packing fraction range, over which shear strain-induced jamming occurs, tends to zero in the large system limit for frictionless packings with overdamped dynamics. PMID- 26871138 TI - Scaling collapse at the jamming transition. AB - The jamming transition of particles with finite-range interactions is characterized by a variety of critical phenomena, including power-law distributions of marginal contacts. We numerically study a recently proposed simple model of jamming, which is conjectured to lie in the same universality class as the jamming of spheres in all dimensions. We extract numerical estimates of the critical exponents, theta=0.451+/-0.006 and gamma=0.404+/-0.004, that match the exponents observed in sphere packing systems. We analyze finite-size scaling effects that manifest in a subcritical cutoff regime and size-independent but protocol-dependent scaling curves. Our results support the conjectured link with sphere jamming, provide more precise measurements of the critical exponents than previously reported, and shed light on the finite-size scaling behavior of continuous constraint satisfiability transitions. PMID- 26871139 TI - Model for the erosion onset of a granular bed sheared by a viscous fluid. AB - We study theoretically the erosion threshold of a granular bed forced by a viscous fluid. We first introduce a model of interacting particles driven on a rough substrate. It predicts a continuous transition at some threshold forcing theta_{c}, beyond which the particle current grows linearly J~theta-theta_{c}. The stationary state is reached after a transient time t_{conv} which diverges near the transition as t_{conv}~|theta-theta_{c}|^{-z} with z~2.5. Both features are consistent with experiments. The model also makes quantitative testable predictions for the drainage pattern: The distribution P(sigma) of local current is found to be extremely broad with P(sigma)~J/sigma, and spatial correlations for the current are negligible in the direction transverse to forcing, but long range parallel to it. We explain some of these features using a scaling argument and a mean-field approximation that builds an analogy with q models. We discuss the relationship between our erosion model and models for the plastic depinning transition of vortex lattices in dirty superconductors, where our results may also apply. PMID- 26871140 TI - Local rheological measurements in the granular flow around an intruder. AB - The rheological properties of granular matter within a two-dimensional flow around a moving disk is investigated experimentally. Using a combination of photoelastic and standard tessellation techniques, the strain and stress tensors are estimated at the grain scale in the time-averaged flow field around a large disk pulled at constant velocity in an assembly of smaller disks. On the one hand, one observes inhomogeneous shear rate and strongly localized shear stress and pressure fields. On the other hand, a significant dilation rate, which has the same magnitude as the shear strain rate, is reported. Significant deviations are observed with local rheology that justify the need of searching for a nonlocal rheology. PMID- 26871142 TI - Turning intractable counting into sampling: Computing the configurational entropy of three-dimensional jammed packings. AB - We present a numerical calculation of the total number of disordered jammed configurations Omega of N repulsive, three-dimensional spheres in a fixed volume V. To make these calculations tractable, we increase the computational efficiency of the approach of Xu et al. [Phys. Rev. Lett. 106, 245502 (2011)10.1103/PhysRevLett.106.245502] and Asenjo et al. [Phys. Rev. Lett. 112, 098002 (2014)10.1103/PhysRevLett.112.098002] and we extend the method to allow computation of the configurational entropy as a function of pressure. The approach that we use computes the configurational entropy by sampling the absolute volume of basins of attraction of the stable packings in the potential energy landscape. We find a surprisingly strong correlation between the pressure of a configuration and the volume of its basin of attraction in the potential energy landscape. This relation is well described by a power law. Our methodology to compute the number of minima in the potential energy landscape should be applicable to a wide range of other enumeration problems in statistical physics, string theory, cosmology, and machine learning that aim to find the distribution of the extrema of a scalar cost function that depends on many degrees of freedom. PMID- 26871141 TI - Transport coefficients of solid particles immersed in a viscous gas. AB - Transport properties of a suspension of solid particles in a viscous gas are studied. The dissipation in such systems arises from two sources: inelasticity in particle collisions and viscous dissipation due to the effect of the gas phase on the particles. Here we consider a simplified case in which the mean relative velocity between the gas and solid phases is taken to be zero, such that "thermal drag" is the only remaining gas-solid interaction. Unlike the previous, more general, treatment of the drag force [Garzo et al., J. Fluid Mech. 712, 129 (2012)]JFLSA70022-112010.1017/jfm.2012.404, here we take into account contributions to the (scaled) transport coefficients eta^{*} (shear viscosity), kappa^{*} (thermal conductivity), and MU^{*} (Dufour-like coefficient) coming from the temperature dependence of the (dimensionless) friction coefficient gamma^{*} characterizing the amplitude of the drag force. At moderate densities, the thermal drag model (which is based on the Enskog kinetic equation) is solved by means of the Chapman-Enskog method and the Navier-Stokes transport coefficients are determined in terms of the coefficient of restitution, the solid volume fraction, and the friction coefficient. The results indicate that the effect of the gas phase on eta^{*} and MU^{*} is non-negligible (especially in the case of relatively dilute systems) while the form of kappa^{*} is the same as the one obtained in the dry granular limit. Finally, as an application of these results, a linear stability analysis of the hydrodynamic equations is carried out to analyze the conditions for stability of the homogeneous cooling state. A comparison with direct numerical simulations shows a good agreement for conditions of practical interest. PMID- 26871143 TI - Head-on collisions of dense granular jets. AB - We study head-on impacts of equal-speed but unequal-width incompressible jets in two dimensions with a focus on dense granular jets. We use discrete particle simulations to show that head-on impact of granular jets produces a quasi-steady state where a fraction of the excess incident momentum from the larger jet is captured by an impact center that drifts steadily over time. By varying the dissipation in our discrete particle simulations and through additional analogous continuum jet impacts of different rheologies, we show that this central drift speed is remarkably dependent primarily on the total dissipation rate to the power 1.5, and largely independent of the dissipation mechanism. We finish by presenting a simple control volume analysis that qualitatively captures the emergence of the drift speed but not the scaling. PMID- 26871144 TI - Mechanical impulse propagation in a three-dimensional packing of spheres confined at constant pressure. AB - Mechanical impulse propagation in granular media depends strongly on the imposed confinement conditions. In this work, the propagation of sound in a granular packing contained by flexible walls that enable confinement under hydrostatic pressure conditions is investigated. This configuration also allows the form of the input impulse to be controlled by means of an instrumented impact pendulum. The main characteristics of mechanical wave propagation are analyzed, and it is found that the wave speed as function of the wave amplitude of the propagating pulse obeys the predictions of the Hertz contact law. Upon increasing the confinement pressure, a continuous transition from nonlinear to linear propagation is observed. Our results show that in the low-confinement regime, the attenuation increases with an increasing impulse amplitude for nonlinear pulses, whereas it is a weak function of the confinement pressure for linear waves. PMID- 26871145 TI - Conical wave propagation and diffraction in two-dimensional hexagonally packed granular lattices. AB - Linear and nonlinear mechanisms for conical wave propagation in two-dimensional lattices are explored in the realm of phononic crystals. As a prototypical example, a statically compressed granular lattice of spherical particles arranged in a hexagonal packing configuration is analyzed. Upon identifying the dispersion relation of the underlying linear problem, the resulting diffraction properties are considered. Analysis both via a heuristic argument for the linear propagation of a wave packet and via asymptotic analysis leading to the derivation of a Dirac system suggests the occurrence of conical diffraction. This analysis is valid for strong precompression, i.e., near the linear regime. For weak precompression, conical wave propagation is still possible, but the resulting expanding circular wave front is of a nonoscillatory nature, resulting from the complex interplay among the discreteness, nonlinearity, and geometry of the packing. The transition between these two types of propagation is explored. PMID- 26871146 TI - Reversible plastic events during oscillatory deformation of amorphous solids. AB - The effect of oscillatory shear strain on nonaffine rearrangements of individual particles in a three-dimensional binary glass is investigated using molecular dynamics simulations. The amorphous material is represented by the Kob-Andersen mixture at the temperature well below the glass transition. We find that during periodic shear deformation of the material, some particles undergo reversible nonaffine displacements with amplitudes that are approximately power-law distributed. Our simulations show that particles with large amplitudes of nonaffine displacement exhibit a collective behavior; namely, they tend to aggregate into relatively compact clusters that become comparable with the system size near the yield strain. Along with reversible displacements there exist a number of irreversible ones. With increasing strain amplitude, the probability of irreversible displacements during one cycle increases, which leads to permanent structural relaxation of the material. PMID- 26871147 TI - Mechanism of chirality conversion by periodic change of temperature: Role of chiral clusters. AB - By grinding crystals in a solution, the chirality of crystal structure (and the molecular chirality for the case of chiral molecules as well) can be converted, and the cause of the phenomenon is attributed to crystal growth with chiral clusters. We show that the recently found chirality conversion with a periodic change of temperature can also be explained by crystal growth with chiral clusters. With the use of a generalized Becker-Doring model, which includes enantio-selective incorporation of small chiral clusters to large solid clusters, the change of cluster distribution and the mass flow between clusters are studied. The chiral clusters act as a reservoir to pump out the minority species to the majority, and the exponential amplification of the enantiomeric excess found in the experiment is reproduced in the numerical calculation. PMID- 26871148 TI - Probabilistic model of waiting times between large failures in sheared media. AB - Using a probabilistic approximation of a mean-field mechanistic model of sheared systems, we analytically calculate the statistical properties of large failures under slow shear loading. For general shear F(t), the distribution of waiting times between large system-spanning failures is a generalized exponential distribution, rho_{T}(t)=lambda(F(t))P(F(t))exp[ ?_{0}^{t}dtaulambda(F(tau))P(F(tau))], where lambda(F(t)) is the rate of small event occurrences at stress F(t) and P(F(t)) is the probability that a small event triggers a large failure. We study the behavior of this distribution as a function of fault properties, such as heterogeneity or shear rate. Because the probabilistic model accommodates any stress loading F(t), it is particularly useful for modeling experiments designed to understand how different forms of shear loading or stress perturbations impact the waiting-time statistics of large failures. As examples, we study how periodic perturbations or fluctuations on top of a linear shear stress increase impact the waiting-time distribution. PMID- 26871149 TI - Richtmyer-Meshkov instability of a three-dimensional SF_{6}-air interface with a minimum-surface feature. AB - The Richmyer-Meshkov instability of a three-dimensional (3D) SF_{6}-air single mode interface with a minimum-surface feature is investigated experimentally. The interface produced by the soap film technique is subjected to a planar shock and the evolution of the shocked interface is captured by time-resolved schlieren photography. Different from the light-heavy single-mode case, a phase inversion occurs in the shock-interface interaction and a bubblelike structure is observed behind the shocked interface, which may be ascribed to the difference in pressure perturbation at different planes. The superimposition of spikelike forward-moving jets forms a complex structure, indicating a distinctly 3D effect. Quantitatively, it is also found that the instability at the symmetry plane grows much slower than the prediction of two-dimensional linear model, but matches the extended 3D linear and nonlinear models accounting for the curvature effects. Therefore, the opposite curvatures of the 3D interface are beneficial for suppressing the growth of the instability. PMID- 26871151 TI - Infrared properties of the energy spectrum in freely decaying isotropic turbulence. AB - The low wave number expansion of the energy spectrum takes the well known form E(k,t)=E_{2}(t)k^{2}+E_{4}(t)k^{4}+?, where the coefficients are weighted integrals against the correlation function C(r,t). We show that expressing E(k,t) in terms of the longitudinal correlation function f(r,t) immediately yields E_{2}(t)=0 by cancellation. We verify that the same result is obtained using the correlation function C(r,t), provided only that f(r,t) falls off faster than r^{ 3} at large values of r. As power-law forms are widely studied for the purpose of establishing bounds, we consider the family of model correlations f(r,t)=alpha_{n}(t)r^{-n}, for positive integer n, at large values of the separation r. We find that for the special case n=3, the relationship connecting f(r,t) and C(r,t) becomes indeterminate, and (exceptionally) E_{2}?0, but that this solution is unphysical in that the viscous term in the Karman-Howarth equation vanishes. Lastly, we show that E_{4}(t) is independent of time, without needing to assume the exponential decrease of correlation functions at large distances. PMID- 26871150 TI - Hydraulic transport across hydrophilic and hydrophobic nanopores: Flow experiments with water and n-hexane. AB - We experimentally explore pressure-driven flow of water and n-hexane across nanoporous silica (Vycor glass monoliths with 7- or 10-nm pore diameters, respectively) as a function of temperature and surface functionalization (native and silanized glass surfaces). Hydraulic flow rates are measured by applying hydrostatic pressures via inert gases (argon and helium, pressurized up to 70 bar) on the upstream side in a capacitor-based membrane permeability setup. For the native, hydrophilic silica walls, the measured hydraulic permeabilities can be quantitatively accounted for by bulk fluidity provided we assume a sticking boundary layer, i.e., a negative velocity slip length of molecular dimensions. The thickness of this boundary layer is discussed with regard to previous capillarity-driven flow experiments (spontaneous imbibition) and with regard to velocity slippage at the pore walls resulting from dissolved gas. Water flow across the silanized, hydrophobic nanopores is blocked up to a hydrostatic pressure of at least 70 bar. The absence of a sticking boundary layer quantitatively accounts for an enhanced n-hexane permeability in the hydrophobic compared to the hydrophilic nanopores. PMID- 26871152 TI - Critical behavior in the inverse to forward energy transition in two-dimensional magnetohydrodynamic flow. AB - We investigate the critical transition from an inverse cascade of energy to a forward energy cascade in a two-dimensional magnetohydrodynamic flow as the ratio of magnetic to mechanical forcing amplitude is varied. It is found that the critical transition is the result of two competing processes. The first process is due to hydrodynamic interactions and cascades the energy to the large scales. The second process couples small-scale magnetic fields to large-scale flows, transferring the energy back to the small scales via a nonlocal mechanism. At marginality the two cascades are both present and cancel each other. The phase space diagram of the transition is sketched. PMID- 26871153 TI - Slip boundary conditions over curved surfaces. AB - Molecular dynamics simulations are used to investigate the influence of surface curvature on the slip boundary condition for a simple fluid. The slip length is measured for flows in planar and cylindrical geometries with a range of wall fluid interactions. As wall curvature increases, the slip length decreases dramatically for closely packed surfaces and increases for sparse ones. The magnitude of the changes depends on the crystallographic orientation and differs for flow along and perpendicular to the direction of curvature. These different patterns of behavior are related to the curvature-induced variation in the ratio of the spacing between fluid atoms to the spacing between minima in the potential from the solid surface. The results are consistent with a microscopic theory for the viscous friction between fluid and wall that expresses the slip length in terms of the lateral response of the fluid to the wall potential and the characteristic decay time of this response. PMID- 26871154 TI - Microelectrokinetic turbulence in microfluidics at low Reynolds number. AB - There is commonly no turbulence in microfluidics, and the flows are believed to be either laminar or chaotic, since Reynolds number (Re) in microflows is usually on the order of unity or lower. However, we recently demonstrated that it is possible to achieve turbulence with low Re (based on the measured flow velocity and the width of the channel entrance) when a pressure-driven flow is electrokinetically forced in a quasi T-microchannel. To be able to measure high frequency velocity fluctuations in microchannels, a velocimeter with submicrometer spatial resolution and microsecond temporal resolution, called a laser-induced fluorescence photobleaching anemometer, is developed. Here we characterize the microelectrokinetic turbulence and observe some typical and important features of high Re flows, such as Kolmogorov -5/3 spectrum of velocity fluctuation, which usually can be realized only at very high Re in macroturbulent flows. PMID- 26871155 TI - Soluble surfactant spreading: How the amphiphilicity sets the Marangoni hydrodynamics. AB - Amphiphiles are molecules combining hydrophilic and hydrophobic parts. The way they arrange in bulk and at interfaces is related to the balance between these two parts, and can be quantified by introducing the critical micellar concentration (cmc). Amphiphiles (also named "surfactants") are also at the origin of dynamical effects: local gradients of interfacial concentrations create the so-called Marangoni flows. Here we study the coupling between the molecule amphiphilicity and these Marangoni flows. We investigate in detail a spreading configuration, where a local excess of surfactants is locally sustained, and follow how these surfactants spread at the interface and diffuse in bulk. We have measured the features of this flow (maximal distance and maximal speed), for different types of surfactant, and as a function of all experimentally available parameters, as well as for two different configurations. In parallel, we propose a detailed hydrodynamical model. For all the measured quantities, we have found a good agreement between the data and the model, evidencing that we have captured the key mechanisms under these spreading experiments. In particular, the cmc turns out to be-as for the static picture of a surfactant-a key element even under dynamical conditions, allowing us to connect the molecule amphiphilicity to its ability to create Marangoni flows. PMID- 26871156 TI - Spreading of turbulence in plane Couette flow. AB - We investigate the growth in the spanwise direction of turbulent spots invading a laminar flow in a plane Couette flow. Direct numerical simulation is used to track the nucleation of streaks during the spot growth. Experiment and direct numerical simulation allow us to study the velocity of the spot fronts and of the vortices observed at the spots' edges. All these results show that two mechanisms are involved when turbulent spots grow: a formerly proposed local growth occurring at the spot spanwise tips but also in comparable proportion a global growth induced by large-scale advection identified in the present work. PMID- 26871157 TI - Transport of inertial particles by viscous streaming in arrays of oscillating probes. AB - A mechanism for the transport of microscale particles in viscous fluids is demonstrated. The mechanism exploits the trapping of such particles by rotational streaming cells established in the vicinity of an oscillating cylinder, recently analyzed in previous work. The present work explores a strategy of transporting particles between the trapping points established by multiple cylinders undergoing oscillations in sequential intervals. It is demonstrated that, by controlling the sequence of oscillation intervals, an inertial particle is effectively and predictably transported between the stable trapping points. Arrays of cylinders in various arrangements are investigated, revealing a technique for constructing arbitrary particle trajectories. It is found that the domain from which particles can be transported and trapped by an oscillator is extended, even to regions in which particles are shielded, by the presence of other stationary cylinders. The timescales for transport are examined, as are the mechanisms by which particles are drawn away from an obstacle toward the trapping point of an oscillator. PMID- 26871158 TI - Power-exponential velocity distributions in disordered porous media. AB - Velocity distribution functions link the micro- and macro-level theories of fluid flow through porous media. Here we study them for the fluid absolute velocity and its longitudinal and lateral components relative to the macroscopic flow direction in a model of a random porous medium. We claim that all distributions follow the power-exponential law controlled by an exponent gamma and a shift parameter u_{0} and examine how these parameters depend on the porosity. We find that gamma has a universal value 1/2 at the percolation threshold and grows with the porosity, but never exceeds 2. PMID- 26871159 TI - Particle stresses in dilute, polydisperse, two-way coupled turbulent flows. AB - Direct numerical simulations are performed of turbulent planar Couette flow which are seeded with two-way coupled particles at low volume concentration. Based on an understanding of the development of particle stress (horizontal momentum carried vertically on average by the particle phase) in monodisperse systems at various particle Stokes numbers, several bidisperse and continuously polydisperse systems are simulated which are chosen to understand how flows containing blends of particle Stokes numbers can be effectively modeled in the dilute regime. Under noninteracting conditions, the particle stresses from particles with different inertia and different feedback stresses are shown to be linearly additive, providing a convenient method for effectively representing dispersed phase stress in polydisperse systems. While this is true, it is demonstrated that a single effective particle size is in general not sufficient at representing the entire mixture. PMID- 26871160 TI - Interparticle collision mechanism in turbulence. AB - Direct numerical simulations of particle-laden homogeneous isotropic turbulence are performed to investigate interparticle collisions in a wide range of Stokes numbers. Dynamics of the particles are described by Stokes drag including particle-particle interactions via hard-sphere collisions, while fluid turbulence is solved using a pseudospectral method. Particular emphasis is placed on interparticle-collision-based conditional statistics of rotation and dissipation rates of the fluid experienced by heavy particles, which provide essential information on the collision process. We also investigate the collision statistics of collision time interval and angle. Based on a Lamb vortex model for a vortex structure, we claim that collision events occur in the edge region for vortical structures in the intermediate-Stokes-number regime, suggesting that the sling effect enhances collision as well as clustering. PMID- 26871161 TI - Structure of sheared and rotating turbulence: Multiscale statistics of Lagrangian and Eulerian accelerations and passive scalar dynamics. AB - The acceleration statistics of sheared and rotating homogeneous turbulence are studied using direct numerical simulation results. The statistical properties of Lagrangian and Eulerian accelerations are considered together with the influence of the rotation to shear ratio, as well as the scale dependence of their statistics. The probability density functions (pdfs) of both Lagrangian and Eulerian accelerations show a strong and similar dependence on the rotation to shear ratio. The variance and flatness of both accelerations are analyzed and the extreme values of the Eulerian acceleration are observed to be above those of the Lagrangian acceleration. For strong rotation it is observed that flatness yields values close to three, corresponding to Gaussian-like behavior, and for moderate and vanishing rotation the flatness increases. Furthermore, the Lagrangian and Eulerian accelerations are shown to be strongly correlated for strong rotation due to a reduced nonlinear term in this case. A wavelet-based scale-dependent analysis shows that the flatness of both Eulerian and Lagrangian accelerations increases as scale decreases, which provides evidence for intermittent behavior. For strong rotation the Eulerian acceleration is even more intermittent than the Lagrangian acceleration, while the opposite result is obtained for moderate rotation. Moreover, the dynamics of a passive scalar with gradient production in the direction of the mean velocity gradient is analyzed and the influence of the rotation to shear ratio is studied. Concerning the concentration of a passive scalar spread by the flow, the pdf of its Eulerian time rate of change presents higher extreme values than those of its Lagrangian time rate of change. This suggests that the Eulerian time rate of change of scalar concentration is mainly due to advection, while its Lagrangian counterpart is only due to gradient production and viscous dissipation. PMID- 26871162 TI - Grouping behavior of coaxial settling particles in a narrow channel. AB - Using numerical simulations, we studied the grouping behaviors of particles settling along their line of centers in narrow channels having a Reynolds number range of 5 <= Re <= 50. The calculations are based on our previously developed lattice Boltzmann direct-forcing-fictitious-domain method. We report the grouping behavior and investigate the dependence on the number of particles n, the initial interparticle separation h_{0}, and the Reynolds number Re. In particular, the mode of grouping is found to be independent of the number of particles when the Reynolds numbers is small. The two lowermost particles always come together first and form a vertical doublet and then the next two lowest particles form another doublet, and so on. Therefore, we observe n/2 doublets or (n-1)/2 doublets when n is even or odd, respectively. The uppermost particle is always left behind when n is odd. Furthermore, the separation between these doublets remains constant, displaying a power-law dependence decreasing from top to bottom. PMID- 26871163 TI - Geometrical properties of turbulent premixed flames and other corrugated interfaces. AB - This study focuses on the geometrical properties of turbulent flame fronts and other interfaces. Toward that end, we use an original tool based on proper orthogonal decomposition (POD), which is applied to the interface spatial coordinates. The focus is mainly on the degree of roughness of the flame front, which is quantified through the scale dependence of its coverage arclength. POD is first validated by comparing with the caliper technique. Fractal characteristics are extracted in an unambiguous fashion using a parametric expression which appears to be impressively well suited for representing Richardson plots. Then it is shown that, for the range of Reynolds numbers investigated here, the scale-by-scale contribution to the arclength does not comply with scale similarity, irrespectively of the type of similarity which is invoked. The finite ratios between large and small scales, referred to as finite Reynolds number effects, are likely to explain this observation. In this context, the Reynolds number that ought to be achieved for a proper inertial range to be discernible, and for scale similarity to be likely to apply, is calculated. Fractal characteristics of flame folding are compared to available predictions. It is confirmed that the inner cutoff satisfactorily correlates with the Kolmogorov scale while the outer cutoff appears to be proportional to the integral length scale. However, the scaling for the fractal dimension is much less obvious. It is argued that much higher Reynolds numbers have to be reached for drawing firm statements about the evolution (or constancy) of the fractal dimension with respect to flame and flow parameters. Finally, a heuristic phenomenology of corrugated interfaces is highlighted. The degree of generality of the latter phenomenology is confirmed by comparing the folding of different interfaces including a turbulent-nonturbulent interface, a liquid jet destabilized by a surrounding air jet, a cavitating flow, and an isoscalar evolving in a turbulent medium. The latter outcome is likely to have strong implications for modeling the corrugation of turbulent interfaces occurring in many physical situations. PMID- 26871164 TI - Evolution of secondary whirls in thermoconvective vortices: Strengthening, weakening, and disappearance in the route to chaos. AB - The appearance, evolution, and disappearance of periodic and quasiperiodic dynamics of fluid flows in a cylindrical annulus locally heated from below are analyzed using nonlinear simulations. The results reveal a route of the transition from a steady axisymmetric vertical vortex to a chaotic flow. The chaotic flow regime is reached after a sequence of successive supercritical Hopf bifurcations to periodic, quasiperiodic, and chaotic flow regimes. A scenario similar to the Ruelle-Takens-Newhouse scenario is verified in this convective flow. In the transition to chaos we find the appearance of subvortices embedded in the primary axisymmetric vortex, flows where the subvortical structure strengthens and weakens, that almost disappears before reforming again, leading to a more disorganized flow to a final chaotic regime. Results are remarkable as they connect to observations describing formation, weakening, and virtual disappearance before revival of subvortices in some atmospheric swirls such as dust devils. PMID- 26871165 TI - Evolution of the single-mode Rayleigh-Taylor instability under the influence of time-dependent accelerations. AB - From nonlinear models and direct numerical simulations we report on several findings of relevance to the single-mode Rayleigh-Taylor (RT) instability driven by time-varying acceleration histories. The incompressible, direct numerical simulations (DNSs) were performed in two (2D) and three dimensions (3D), and at a range of density ratios of the fluid combinations (characterized by the Atwood number). We investigated several acceleration histories, including acceleration profiles of the general form g(t)~t^{n}, with n>=0 and acceleration histories reminiscent of the linear electric motor experiments. For the 2D flow, results from numerical simulations compare well with a 2D potential flow model and solutions to a drag-buoyancy model reported as part of this work. When the simulations are extended to three dimensions, bubble and spike growth rates are in agreement with the so-called level 2 and level 3 models of Mikaelian [K. O. Mikaelian, Phys. Rev. E 79, 065303(R) (2009)10.1103/PhysRevE.79.065303], and with corresponding 3D drag-buoyancy model solutions derived in this article. Our generalization of the RT problem to study variable g(t) affords us the opportunity to investigate the appropriate scaling for bubble and spike amplitudes under these conditions. We consider two candidates, the displacement Z and width s^{2}, but find the appropriate scaling is dependent on the density ratios between the fluids-at low density ratios, bubble and spike amplitudes are explained by both s^{2} and Z, while at large density differences the displacement collapses the spike data. Finally, for all the acceleration profiles studied here, spikes enter a free-fall regime at lower Atwood numbers than predicted by all the models. PMID- 26871166 TI - Continuation and stability of convective modulated rotating waves in spherical shells. AB - Modulated rotating waves (MRW), bifurcated from the thermal-Rossby waves that arise at the onset of convection of a fluid contained in a rotating spherical shell, and their stability, are studied. For this purpose, Newton-Krylov continuation techniques are applied. Nonslip boundary conditions, an Ekman number E=10^{-4}, and a low Prandtl number fluid Pr=0.1 in a moderately thick shell of radius ratio eta=0.35, differentially heated, are considered. The MRW are obtained as periodic orbits by rewriting the equations of motion in the rotating frame of reference where the rotating waves become steady states. Newton-Krylov continuation allows us to obtain unstable MRW that cannot be found by using only time integrations, and identify regions of multistability. For instance, unstable MRW without any azimuthal symmetry have been computed. It is shown how they become stable in a small Rayleigh-number interval, in which two branches of traveling waves are also stable. The study of the stability of the MRW helps to locate and classify the large sequence of bifurcations, which takes place in the range analyzed. In particular, tertiary Hopf bifurcations giving rise to three frequency stable solutions are accurately determined. PMID- 26871167 TI - Metallic-thin-film instability with spatially correlated thermal noise. AB - We study the effects of stochastic thermal fluctuations on the instability of the free surface of a flat liquid metallic film on a solid substrate. These fluctuations are represented by a stochastic noise term added to the deterministic equation for the film thickness within the long-wave approximation. Unlike the case of polymeric films, we find that this noise, while remaining white in time, must be colored in space, at least in some regimes. The corresponding noise term is characterized by a nonzero correlation length, l_{c}, which, combined with the size of the system, leads to a dimensionless parameter beta that accounts for the relative importance of the spatial correlation (beta~l_{c}^{-1}). We perform the linear stability analysis (LSA) of the film both with and without the noise term and find that for l_{c} larger than some critical value (depending on the system size), the wavelength of the peak of the spectrum is larger than that corresponding to the deterministic case, while for smaller l_{c} this peak corresponds to smaller wavelength than the latter. Interestingly, whatever the value of l_{c}, the peak always approaches the deterministic one for larger times. We compare LSA results with the numerical simulations of the complete nonlinear problem and find a good agreement in the power spectra for early times at different values of beta. For late times, we find that the stochastic LSA predicts well the position of the dominant wavelength, showing that nonlinear interactions do not modify the trends of the early linear stages. Finally, we fit the theoretical spectra to experimental data from a nanometric laser-melted copper film and find that at later times, the adjustment requires smaller values of beta (larger space correlations). PMID- 26871168 TI - Diffuse interface method for a compressible binary fluid. AB - Multicomponent, multiphase, compressible flows are very important in real life, as well as in scientific research, while their modeling is in an early stage. In this paper, we propose a diffuse interface model for compressible binary mixtures, based on the balance of mass, momentum, energy, and the second law of thermodynamics. We show both analytically and numerically that this model is able to describe the phase equilibrium for a real binary mixture (CO_{2} + ethanol is considered in this paper) very well by adjusting the parameter which measures the attraction force between molecules of the two components in the model. We also show that the calculated surface tension of the CO_{2} + ethanol mixture at different concentrations match measurements in the literature when the mixing capillary coefficient is taken to be the geometric mean of the capillary coefficient of each component. Three different cases of two droplets in a shear flow, with the same or different concentration, are simulated, showing that the higher concentration of CO_{2} the smaller the surface tension and the easier the drop deforms. PMID- 26871169 TI - Statistics of highly heterogeneous flow fields confined to three-dimensional random porous media. AB - We present a strong relationship between the microstructural characteristics of, and the fluid velocity fields confined to, three-dimensional random porous materials. The relationship is revealed through simultaneously extracting correlation functions R_{uu}(r) of the spatial (Eulerian) velocity fields and microstructural two-point correlation functions S_{2}(r) of the random porous heterogeneous materials. This demonstrates that the effective physical transport properties depend on the characteristics of complex pore structure owing to the relationship between R_{uu}(r) and S_{2}(r) revealed in this study. Further, the mean excess plot was used to investigate the right tail of the streamwise velocity component that was found to obey light-tail distributions. Based on the mean excess plot, a generalized Pareto distribution can be used to approximate the positive streamwise velocity distribution. PMID- 26871170 TI - Thin three-dimensional droplets on an oscillating substrate with contact angle hysteresis. AB - Recent experiments [P. Brunet, J. Eggers, and R. D. Deegan, Phys. Rev. Lett. 99, 144501 (2007)10.1103/PhysRevLett.99.144501] have shown that a liquid droplet on an inclined plane can be made to move uphill by sufficiently strong, vertical oscillations. In order to investigate this counterintuitive phenomenon we use a model in which liquid inertia and viscosity are assumed negligible so that the motion of the droplet is dominated by the applied acceleration due to the oscillation of the plate, gravity, and surface tension. We explain how the leading order motion of the droplet can be separated into a spreading mode and a swaying mode. For a linear contact line law, the maximum rise velocity occurs when these modes are in phase. We show that, both with and without contact angle hysteresis, the droplet can climb uphill and also that, for certain contact line laws, the motion of the droplet can produce footprints similar to experimental results. We show that if the two modes are out of phase when there is no contact angle hysteresis, the inclusion of hysteresis can force them into phase. This in turn increases the rise velocity of the droplet and can, in some cases, cause a sliding droplet to climb. PMID- 26871171 TI - Nanoscale dynamics of Joule heating and bubble nucleation in a solid-state nanopore. AB - We present a mathematical model for Joule heating of an electrolytic solution in a nanopore. The model couples the electrical and thermal dynamics responsible for rapid and extreme superheating of the electrolyte within the nanopore. The model is implemented numerically with a finite element calculation, yielding a time and spatially resolved temperature distribution in the nanopore region. Temperatures near the thermodynamic limit of superheat are predicted to be attained just before the explosive nucleation of a vapor bubble is observed experimentally. Knowledge of this temperature distribution enables the evaluation of related phenomena including bubble nucleation kinetics, relaxation oscillation, and bubble dynamics. PMID- 26871172 TI - Spatiotemporal instability of an electrified falling film. AB - The linear spatiotemporal response to an infinitesimal disturbance is analyzed for an electrified falling film based on the Orr-Sommerfeld boundary value problem. Four spatial branches are identified, which lose their spatial symmetry in the presence of an electric field. In addition, the absolute and convective instabilities are studied within the frameworks of the saddle point approach and the collision criterion. The collision criterion offers two unstable branches that characterize the exact range of the unstable wave packet that is diminished in the presence of an electric field. In contrast, the saddle point approach offers only one unstable branch. The associated unstable range of the wave packet is similar to that predicted by the collision criterion only when the electric field is enhanced. It is shown that the electrified falling film is convectively unstable. PMID- 26871173 TI - Phase-field theory of multicomponent incompressible Cahn-Hilliard liquids. AB - In this paper, a generalization of the Cahn-Hilliard theory of binary liquids is presented for multicomponent incompressible liquid mixtures. First, a thermodynamically consistent convection-diffusion-type dynamics is derived on the basis of the Lagrange multiplier formalism. Next, a generalization of the binary Cahn-Hilliard free-energy functional is presented for an arbitrary number of components, offering the utilization of independent pairwise equilibrium interfacial properties. We show that the equilibrium two-component interfaces minimize the functional, and we demonstrate that the energy penalization for multicomponent states increases strictly monotonously as a function of the number of components being present. We validate the model via equilibrium contact angle calculations in ternary and quaternary (four-component) systems. Simulations addressing liquid-flow-assisted spinodal decomposition in these systems are also presented. PMID- 26871174 TI - Self-similar propagation of Hermite-Gauss water-wave pulses. AB - We demonstrate both theoretically and experimentally propagation dynamics of surface gravity water-wave pulses, having Hermite-Gauss envelopes. We show that these waves propagate self-similarly along an 18-m wave tank, preserving their general Hermite-Gauss envelopes in both the linear and the nonlinear regimes. The measured surface elevation wave groups enable observing the envelope phase evolution of both nonchirped and linearly frequency chirped Hermite-Gauss pulses, hence allowing us to measure Gouy phase shifts of high-order Hermite-Gauss pulses for the first time. Finally, when increasing pulse amplitude, nonlinearity becomes essential and the second harmonic of Hermite-Gauss waves was observed. We further show that these generated second harmonic bound waves still exhibit self similar Hermite-Gauss shapes along the tank. PMID- 26871175 TI - Gas flow through rough microchannels in the transition flow regime. AB - A multiple-relaxation-time lattice Boltzmann model of Couette flow is developed to investigate the rarified gas flow through microchannels with roughness characterized by fractal geometry, especially to elucidate the coupled effects of roughness and rarefaction on microscale gas flow in the transition flow regime. The results indicate that the surface roughness effect on gas flow behavior becomes more significant in rarefied gas flow with the increase of Knudsen number. We find the gas flow behavior in the transition flow regime is more sensitive to roughness height than that in the slip flow regime. In particular, the influence of fractal dimension on rarefied gas flow behavior is less significant than roughness height. PMID- 26871176 TI - Ferrofluid patterns in Hele-Shaw cells: Exact, stable, stationary shape solutions. AB - We investigate a quasi-two-dimensional system composed of an initially circular ferrofluid droplet surrounded by a nonmagnetic fluid of higher density. These immiscible fluids flow in a rotating Hele-Shaw cell, under the influence of an in plane radial magnetic field. We focus on the situation in which destabilizing bulk magnetic field effects are balanced by stabilizing centrifugal forces. In this framing, we consider the interplay of capillary and magnetic normal traction effects in determining the fluid-fluid interface morphology. By employing a vortex-sheet formalism, we have been able to find a family of exact stationary N fold polygonal shape solutions for the interface. A weakly nonlinear theory is then used to verify that such exact interfacial solutions are in fact stable. PMID- 26871177 TI - Pair creation in collision of gamma-ray beams produced with high-intensity lasers. AB - Direct production of electron-positron pairs in two-photon collisions, the Breit Wheeler process, is one of the basic processes in the universe. However, it has never been directly observed in the laboratory because of the absence of the intense gamma-ray sources. Laser-induced synchrotron sources emission may open a way to observe this process. The feasibility of an experimental setup using a MeV photon source is studied in this paper. We compare several gamma-ray sources and estimate the expected number of electron-positron pairs and competing processes by using numerical simulations including quantum electrodynamic effects. PMID- 26871178 TI - Avalanche structural rearrangement through cracking-healing in weakly stressed cold dusty plasma liquids. AB - We experimentally investigate the spatiotemporal dynamical behaviors of the avalanche structural rearrangement through micro-cracking-healing in weakly stressed cold dusty plasma liquids, and the kinetic origins for their different spatial and temporal classifications. The crystalline ordered domains can be cracked or temporarily sustain and transfer the weak stress to remote regions for cracking-healing. It is found that cracking sites form a fractal network with cluster size following power law distribution in the xyt space. The histograms of the persistent times for sustaining regional ordered and disordered structure, the temporal cracking burst width, and quiescent time between two bursts all follow power law decays with fast descending tails. Cracking can be classified into a single temporal burst with simple line like spatial patterns and the successive cracking fluctuation with densely packed cracking clusters. For an ordered region, whether the Burgers vectors of the incoming dislocations from the boundary allow direct dislocation reduction is the key for the above two classifications through cracking a large ordered domain into medium scale corotating ordered domains or small patches. The low regional structural order at the end of a cracking burst can be regarded as an alarm for predicting the short quiescent period before the next cracking burst. PMID- 26871179 TI - Fast magnetic-field annihilation in the relativistic collisionless regime driven by two ultrashort high-intensity laser pulses. AB - The magnetic quadrupole structure formation during the interaction of two ultrashort high power laser pulses with a collisionless plasma is demonstrated with 2.5-dimensional particle-in-cell simulations. The subsequent expansion of the quadrupole is accompanied by magnetic-field annihilation in the ultrarelativistic regime, when the magnetic field cannot be sustained by the plasma current. This results in a dominant contribution of the displacement current exciting a strong large scale electric field. This field leads to the conversion of magnetic energy into kinetic energy of accelerated electrons inside the thin current sheet. PMID- 26871180 TI - Anisotropic confinement effects in a two-dimensional plasma crystal. AB - The spectral asymmetry of the wave-energy distribution of dust particles during mode-coupling-induced melting, observed for the first time in plasma crystals by Couedel et al. [Phys. Rev. E 89, 053108 (2014)PLEEE81539 375510.1103/PhysRevE.89.053108], is studied theoretically and by molecular dynamics simulations. It is shown that an anisotropy of the well confining the microparticles selects the directions of preferred particle motion. The observed differences in intensity of waves of opposed directions are explained by a nonvanishing phonon flux. Anisotropic phonon scattering by defects and Umklapp scattering are proposed as possible reasons for the mean phonon flux. PMID- 26871181 TI - Evolution of a plasma vortex in air. AB - We report the generation of a vortex-shaped plasma in air by using a capacitively coupled dielectric barrier discharge system. We show that a vortex-shaped plasma can be produced inside a helium gas vortex and is capable of propagating for 3 cm. The fluctuation of the plasma ring shows a scaling relation with the Reynolds number of the vortex. The transient discharge reveals the property of corona discharge, where the conducting channel within the gas vortex and the blur plasma emission are observed at each half voltage cycle. PMID- 26871182 TI - Cross-field transport in Goldreich-Sridhar magnetohydrodynamic turbulence. AB - I derive analytically the temporal dependence of the perpendicular transport coefficient of a charged particle in the three-dimensional anisotropic turbulence conjectured by Goldreich-Sridhar by implementing multispacecraft constraints on the turbulence power spectrum. The particle motion away from the turbulent local field line is assessed as gradient-curvature drift of the guiding center and compared with the magnetic field line random walk. At inertial scales much smaller than the turbulence outer scale, particles decorrelate from field lines in a free-streaming motion, with no diffusion. In the solar wind at 1 AU, for energy sufficiently small (<1 keV protons), the perpendicular average displacement due to field line tangling generally dominates over two decades of turbulent scales. However, for higher energies (?25 MeV protons) within the range of multispacecraft measurements, the longitudinal spread originating from transport due to gradient-curvature drift reaches up to ?10^{?}-20^{?}. This result highlights the role of perpendicular transport in the interpretation of interplanetary and interstellar data. PMID- 26871183 TI - Attospiral generation upon interaction of circularly polarized intense laser pulses with conelike targets. AB - The generation of high-intensity attopulses has been investigated in cylindrical geometry by using a three-dimensional particle-in-cell plasma simulation code. Due to the rotation-symmetric target, a circularly polarized laser pulse is considered, propagating on the axis of a hollow conelike target. The large incidence angle and constant ponderomotive pressure lead to nanobunching of relativistic electrons responsible for the laser-driven synchrotron emission. A numerical method is developed to find the source and direction of the coherent radiation that ensures the existence of attopulses. The intensity modulation in the harmonic spectrum is well described by the model of coherent synchrotron emission extended to the regime of higher order gamma spikes. The spatial distribution of the higher harmonics resembles a spiral shape which gets focused into a small volume behind the target. PMID- 26871184 TI - Interaction-induced nonlinear refractive-index reduction of gases in the midinfrared regime. AB - The nonlinear optical response of a dilute atomic gas to ultrashort high intensity midinfrared pulse excitation is calculated fully microscopically. The optically induced polarization dynamics is evaluated for the interacting many electron system in a gas of hydrogen atoms. It is shown that the many-body effects during the excitation distinctly influence not only the atomic ionization dynamics, but also the nonlinear polarization response in the midinfrared regime. The delicate balance between the Kerr focusing and the ionization-induced defocusing is dramatically modified and a significant decrease of the nonlinear refractive index is predicted for increasing wavelength of the exciting pulse. PMID- 26871185 TI - Molecular dynamics simulations of bubble nucleation in dark matter detectors. AB - Bubble chambers and droplet detectors used in dosimetry and dark matter particle search experiments use a superheated metastable liquid in which nuclear recoils trigger bubble nucleation. This process is described by the classical heat spike model of F. Seitz [Phys. Fluids (1958-1988) 1, 2 (1958)PFLDAS0031 917110.1063/1.1724333], which uses classical nucleation theory to estimate the amount and the localization of the deposited energy required for bubble formation. Here we report on direct molecular dynamics simulations of heat-spike induced bubble formation. They allow us to test the nanoscale process described in the classical heat spike model. 40 simulations were performed, each containing about 20 million atoms, which interact by a truncated force-shifted Lennard-Jones potential. We find that the energy per length unit needed for bubble nucleation agrees quite well with theoretical predictions, but the allowed spike length and the required total energy are about twice as large as predicted. This could be explained by the rapid energy diffusion measured in the simulation: contrary to the assumption in the classical model, we observe significantly faster heat diffusion than the bubble formation time scale. Finally we examine alpha-particle tracks, which are much longer than those of neutrons and potential dark matter particles. Empirically, alpha events were recently found to result in louder acoustic signals than neutron events. This distinction is crucial for the background rejection in dark matter searches. We show that a large number of individual bubbles can form along an alpha track, which explains the observed larger acoustic amplitudes. PMID- 26871186 TI - Determination of macroscopic transport coefficients of a dissipative particle dynamics solvent. AB - We present an approach to determine macroscopic transport coefficients of a dissipative particle dynamics (DPD) solvent. Shear viscosity, isothermal speed of sound, and bulk viscosity result from DPD-model input parameters and can be determined only a posteriori. For this reason approximate predictions of these quantities are desirable in order to set appropriate DPD input parameters. For the purpose of deriving an improved approximate prediction we analyze the autocorrelation of shear and longitudinal modes in Fourier space of a DPD solvent for Kolmogorov flow. We propose a fitting function with nonexponential properties which gives a good approximation to these autocorrelation functions. Given this fitting function we improve significantly the capability of a priori determination of macroscopic solvent transport coefficients in comparison to previously used exponential fitting functions. PMID- 26871187 TI - Multipseudopotential interaction: A consistent study of cubic equations of state in lattice Boltzmann models. AB - A method is developed to analytically and consistently implement cubic equations of state into the recently proposed multipseudopotential interaction (MPI) scheme in the class of two-phase lattice Boltzmann (LB) models [S. Khajepor, J. Wen, and B. Chen, Phys. Rev. E 91, 023301 (2015)]10.1103/PhysRevE.91.023301. An MPI forcing term is applied to reduce the constraints on the mathematical shape of the thermodynamically consistent pseudopotentials; this allows the parameters of the MPI forces to be determined analytically without the need of curve fitting or trial and error methods. Attraction and repulsion parts of equations of state (EOSs), representing underlying molecular interactions, are modeled by individual pseudopotentials. Four EOSs, van der Waals, Carnahan-Starling, Peng-Robinson, and Soave-Redlich-Kwong, are investigated and the results show that the developed MPI LB system can satisfactorily recover the thermodynamic states of interest. The phase interface is predicted analytically and controlled via EOS parameters independently and its effect on the vapor-liquid equilibrium system is studied. The scheme is highly stable to very high density ratios and the accuracy of the results can be enhanced by increasing the interface resolution. The MPI drop is evaluated with regard to surface tension, spurious velocities, isotropy, dynamic behavior, and the stability dependence on the relaxation time. PMID- 26871188 TI - Computational dynamics of acoustically driven microsphere systems. AB - We propose a computational framework for the self-consistent dynamics of a microsphere system driven by a pulsed acoustic field in an ideal fluid. Our framework combines a molecular dynamics integrator describing the dynamics of the microsphere system with a time-dependent integral equation solver for the acoustic field that makes use of fields represented as surface expansions in spherical harmonic basis functions. The presented approach allows us to describe the interparticle interaction induced by the field as well as the dynamics of trapping in counter-propagating acoustic pulses. The integral equation formulation leads to equations of motion for the microspheres describing the effect of nondissipative drag forces. We show (1) that the field-induced interactions between the microspheres give rise to effective dipolar interactions, with effective dipoles defined by their velocities and (2) that the dominant effect of an ultrasound pulse through a cloud of microspheres gives rise mainly to a translation of the system, though we also observe both expansion and contraction of the cloud determined by the initial system geometry. PMID- 26871189 TI - Wideband analytical equivalent circuit for one-dimensional periodic stacked arrays. AB - A wideband equivalent circuit is proposed for the accurate analysis of scattering from a set of stacked slit gratings illuminated by a plane wave with transverse magnetic or electric polarization that impinges normally or obliquely along one of the principal planes of the structure. The slit gratings are printed on dielectric slabs of arbitrary thickness, including the case of closely spaced gratings that interact by higher-order modes. A Pi-circuit topology is obtained for a pair of coupled arrays, with fully analytical expressions for all the circuit elements. This equivalent Pi circuit is employed as the basis to derive the equivalent circuit of finite stacks with any given number of gratings. Analytical expressions for the Brillouin diagram and the Bloch impedance are also obtained for infinite periodic stacks. PMID- 26871191 TI - Lattice Boltzmann modeling of three-phase incompressible flows. AB - In this paper, based on multicomponent phase-field theory we intend to develop an efficient lattice Boltzmann (LB) model for simulating three-phase incompressible flows. In this model, two LB equations are used to capture the interfaces among three different fluids, and another LB equation is adopted to solve the flow field, where a new distribution function for the forcing term is delicately designed. Different from previous multiphase LB models, the interfacial force is not used in the computation of fluid velocity, which is more reasonable from the perspective of the multiscale analysis. As a result, the computation of fluid velocity can be much simpler. Through the Chapman-Enskog analysis, it is shown that the present model can recover exactly the physical formulations for the three-phase system. Numerical simulations of extensive examples including two circular interfaces, ternary spinodal decomposition, spreading of a liquid lens, and Kelvin-Helmholtz instability are conducted to test the model. It is found that the present model can capture accurate interfaces among three different fluids, which is attributed to its algebraical and dynamical consistency properties with the two-component model. Furthermore, the numerical results of three-phase flows agree well with the theoretical results or some available data, which demonstrates that the present LB model is a reliable and efficient method for simulating three-phase flow problems. PMID- 26871190 TI - Reaction rates for a generalized reaction-diffusion master equation. AB - It has been established that there is an inherent limit to the accuracy of the reaction-diffusion master equation. Specifically, there exists a fundamental lower bound on the mesh size, below which the accuracy deteriorates as the mesh is refined further. In this paper we extend the standard reaction-diffusion master equation to allow molecules occupying neighboring voxels to react, in contrast to the traditional approach, in which molecules react only when occupying the same voxel. We derive reaction rates, in two dimensions as well as three dimensions, to obtain an optimal match to the more fine-grained Smoluchowski model and show in two numerical examples that the extended algorithm is accurate for a wide range of mesh sizes, allowing us to simulate systems that are intractable with the standard reaction-diffusion master equation. In addition, we show that for mesh sizes above the fundamental lower limit of the standard algorithm, the generalized algorithm reduces to the standard algorithm. We derive a lower limit for the generalized algorithm which, in both two dimensions and three dimensions, is of the order of the reaction radius of a reacting pair of molecules. PMID- 26871192 TI - Multiscale modeling of dislocation-precipitate interactions in Fe: From molecular dynamics to discrete dislocations. AB - The stress-driven motion of dislocations in crystalline solids, and thus the ensuing plastic deformation process, is greatly influenced by the presence or absence of various pointlike defects such as precipitates or solute atoms. These defects act as obstacles for dislocation motion and hence affect the mechanical properties of the material. Here we combine molecular dynamics studies with three dimensional discrete dislocation dynamics simulations in order to model the interaction between different kinds of precipitates and a 1/2<111>{110} edge dislocation in BCC iron. We have implemented immobile spherical precipitates into the ParaDis discrete dislocation dynamics code, with the dislocations interacting with the precipitates via a Gaussian potential, generating a normal force acting on the dislocation segments. The parameters used in the discrete dislocation dynamics simulations for the precipitate potential, the dislocation mobility, shear modulus, and dislocation core energy are obtained from molecular dynamics simulations. We compare the critical stresses needed to unpin the dislocation from the precipitate in molecular dynamics and discrete dislocation dynamics simulations in order to fit the two methods together and discuss the variety of the relevant pinning and depinning mechanisms. PMID- 26871193 TI - Nonparametric k-nearest-neighbor entropy estimator. AB - A nonparametric k-nearest-neighbor-based entropy estimator is proposed. It improves on the classical Kozachenko-Leonenko estimator by considering nonuniform probability densities in the region of k-nearest neighbors around each sample point. It aims to improve the classical estimators in three situations: first, when the dimensionality of the random variable is large; second, when near functional relationships leading to high correlation between components of the random variable are present; and third, when the marginal variances of random variable components vary significantly with respect to each other. Heuristics on the error of the proposed and classical estimators are presented. Finally, the proposed estimator is tested for a variety of distributions in successively increasing dimensions and in the presence of a near-functional relationship. Its performance is compared with a classical estimator, and a significant improvement is demonstrated. PMID- 26871194 TI - Erratum: Transport and diffusion properties of interacting colloidal particles in two-dimensional microchannels with a periodic potential [Phys. Rev. E 91, 022313 (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevE.91.022313. PMID- 26871195 TI - Publisher's Note: Curvature-induced crosshatched order in two-dimensional semiflexible polymer networks [Phys. Rev. E 92, 060602(R) (2015)]. AB - This corrects the article DOI: 10.1103/PhysRevE.92.060602. PMID- 26871196 TI - Effects of isoquinoline alkaloid berberine on lipid peroxidation, antioxidant defense system, and liver damage induced by lead acetate in rats. AB - OBJECTIVES: Liver is considered a target organ affected by lead toxicity. Oxidative stress is among the mechanisms involved in liver damage. Here we investigated the effects of the natural alkaloid berberine on oxidative stress and hepatotoxicity induced by lead in rats. METHODS: Animals received an aqueous solution of lead acetate (500 mg Pb/l in the drinking water) and/or daily oral gavage of berberine (50 mg/kg) for 8 weeks. Rats were then weighed and used for the biochemical, molecular, and histological evaluations. RESULTS: Lead-induced oxidative stress, shown by increasing lipid peroxidation along with a concomitant decrease in hepatic levels of thiol groups, total antioxidant capacity, the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, and reduced versus oxidized glutathione ratio. Berberine corrected all the disturbances in oxidative stress markers induced by lead administration. Berberine also prevented the elevated levels of enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) and the decrease in body weight and albumin. The protective effects of berberine were comparable with silymarin. Furthermore, berberine attenuated liver damage, shown by decreased necrosis and inflammatory cell infiltration. DISCUSSION: Berberine represents a potential therapeutic option against lead-induced hepatotoxicity through inhibiting lipid peroxidation and enhancing antioxidant defenses. CONCLUSION: Berberine exerted protective effects on lead-induced oxidative stress and hepatotoxicity in rats. PMID- 26871197 TI - Combination of low-dose imatinib plus nilotinib for the treatment of chronic phase chronic myeloid leukaemia after imatinib failure. AB - OBJECTIVES: This is a feasibility study to evaluate whether simultaneous administration of low doses of imatinib and nilotinib in chronic-phase chronic myeloid leukaemia (CP-CML) patients has the potential for transcript elimination after failure to imatinib. METHODS: Ten patients were enrolled; eight had cytogenetic relapse and two had confirmed loss of major molecular response (MMR). At baseline, BCR-ABL kinase domain mutation was detected in four patients. RESULTS: After 6 months of therapy, major cytogenetic response, complete cytogenetic response, and MMR were achieved in seven, four, and four patients, respectively. Grade 4 thrombocytopenia developed in one patient, and grade 1 skin rash in four. DISCUSSION AND CONCLUSION: These results suggest that imatinib might have inhibitory effects on the clearance of nilotinib, increasing its efficacy. This dual therapy was well tolerated and resulted in improvement of cytogenetic and molecular responses in patients with CP-CML after failure to imatinib. ClinicalTrials.gov registration number: NCT01819389. PMID- 26871198 TI - Extrapyramidal Symptoms as a Result of Risperidone Discontinuation During Combination Therapy with Methylphenidate in a Pediatric Patient. PMID- 26871199 TI - Pharmacogenomics of anti-TNF response in psoriasis, where are we? PMID- 26871200 TI - Murine liver damage caused by exposure to nano-titanium dioxide. AB - Due to its unique physiochemical properties, nano-titanium dioxide (nano-TiO2) is widely used in all aspects of people's daily lives, bringing it into increasing contact with humans. Thus, this material's security issues for humans have become a heavily researched subject. Nano-TiO2 can enter the body through the mouth, skin, respiratory tract or in other ways, after which it enters the blood circulation and is deposited in the liver, changing biochemical indicators and causing liver inflammation. Meanwhile, the light sensitivity of these nanoparticles allows them to become media-generating reactive oxygen species (ROS), causing an imbalance between oxidation and anti-oxidation that leads to oxidative stress and liver damage. Nano-TiO2 can be transported into cells via phagocytosis, where the nanoparticles bind to the mitochondrial membrane, resulting in the disintegration of the membrane and the electron transport chain within the mitochondria. Thus, more ROS are produced. Nano-TiO2 can also enter the nucleus, where it can directly embed into or indirectly affect DNA, thereby causing DNA breakage or affecting gene expression. These effects include increased mRNA and protein expression levels of inflammation-related factors and decreased mRNA and protein expression levels of IkappaB and IL-2, resulting in inflammation. Long-term inflammation of the liver causes HSC cell activation, and extracellular matrix (ECM) deposition is promoted by multiple signalling pathways, resulting in liver fibrosis. In this paper, the latest progress on murine liver injury induced by environmental TiO2 is systematically described. The toxicity of nano-TiO2 also depends on size, exposure time, surface properties, dosage, administration route, and its surface modification. Therefore, its toxic effects in humans should be studied in greater depth. This paper also provides useful reference information regarding the safe use of nano TiO2 in the future. PMID- 26871201 TI - Perioperative pregabalin for reducing pain, analgesic consumption, and anxiety and enhancing sleep quality in elective neurosurgical patients: a prospective, randomized, double-blind, and controlled clinical study. AB - OBJECTIVE The aim of this study was to assess in-hospital (immediate) postoperative pain scores and analgesic consumption (primary goals) and preoperative anxiety and sleep quality (secondary goals) in patients who underwent craniotomy and were treated with pregabalin (PGL). Whenever possible, out-of-hospital pain scores and analgesics usage data were obtained as well. METHODS This prospective, randomized, double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014. Patients received either 150 mg PGL (n = 50) or 500 mg starch (placebo; n = 50) on the evening before surgery, 1.5 hours before surgery, and twice daily for 72 hours following surgery. All patients spent the night before surgery in the hospital, and no other premedication was administered. Opioids and nonsteroidal antiinflammatory drugs were used for pain, which was self-rated by means of a numerical rating scale (score range 0-10). RESULTS Eighty-eight patients completed the study. Data on the American Society of Anesthesiologists class, age, body weight, duration of surgery, and intraoperative drugs were similar for both groups. The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group (p < 0.01). Analgesic consumption was also lower in the PGL group, both immediately and 1 month after surgery. There were fewer requests for antiemetics in the PGL group, and the rate of postoperative nausea and vomiting was lower. The preoperative anxiety level and the quality of sleep were significantly better in the PGL group (p < 0.01). There were no PGL-associated major adverse events. CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety, improves sleep quality, and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects. Clinical trial registration no.: NCT01612832 ( clinicaltrials.gov ). PMID- 26871203 TI - One-year outcome in patients with idiopathic normal-pressure hydrocephalus: comparison of lumboperitoneal shunt to ventriculoperitoneal shunt. AB - OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is treated with cerebrospinal fluid shunting, and implantation of a ventriculoperitoneal shunt (VPS) is the current standard treatment. The objective of this study was to compare the efficacy and safety of VPSs and lumboperitoneal shunts (LPSs) for patients with iNPH. METHODS The authors conducted a prospective multicenter study of LPS use for patients with iNPH. Eighty-three patients with iNPH (age 60 to 85 years) who presented with ventriculomegaly and high-convexity and medial subarachnoid space tightness on MR images were recruited from 20 neurological or neurosurgical centers in Japan between March 1, 2010, and October 19, 2011. The primary outcome was the modified Rankin Scale (mRS) score 1 year after surgery, and the secondary outcome included scores on the iNPH grading scale (iNPHGS). A previously conducted VPS cohort study with the same inclusion criteria and primary and secondary end points was used as a historical control. RESULTS The proportion of patients who achieved a favorable outcome (i.e., improvement of at least 1 point in their mRS score) was 63% (95% CI 51%-73%) and was comparable to values reported with VPS implantation (69%, 95% CI 59%-78%). Using the iNPHGS, the 1-year improvement rate was 75% (95% CI 64%-84%) and was comparable to the rate found in the VPS study (77%, 95% CI 68%-84%). The proportion of patients experiencing serious adverse events (SAEs) and non-SAEs did not differ significantly between the groups at 1 year after surgery (SAEs: 19 [22%] of 87 LPS patients vs 15 [15%] of 100 VPS patients, p = 0.226; non-SAEs: 24 [27.6%] LPS patients vs 20 [20%] VPS patients, p = 0.223). However, shunt revisions were more common in LPS-treated patients than in VPS-treated patients (6 [7%] vs 1 [1%]). CONCLUSIONS The efficacy and safety rates for LPSs with programmable valves are comparable to those for VPSs for the treatment of patients with iNPH. Despite the relatively high shunt failure rate, an LPS can be the treatment of choice because of its minimal invasiveness and avoidance of brain injury. PMID- 26871202 TI - Association of nosocomial infections with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage. AB - OBJECTIVE Delayed cerebral ischemia (DCI) is a recognized complication of aneurysmal subarachnoid hemorrhage (aSAH) that contributes to poor outcome. This study seeks to determine the effect of nosocomial infection on the incidence of DCI and patient outcome. METHODS An exploratory analysis was performed on 156 patients with aSAH enrolled in the Cerebral Aneurysm Renin Angiotensin System study. Clinical and radiographic data were analyzed with univariate analysis to detect risk factors for the development of DCI and poor outcome. Multivariate logistic regression was performed to identify independent predictors of DCI. RESULTS One hundred fifty-three patients with aSAH were included. DCI was identified in 32 patients (20.9%). Nosocomial infection (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.09-11.2, p = 0.04), ventriculitis (OR 25.3, 95% CI 1.39-458.7, p = 0.03), aneurysm re-rupture (OR 7.55, 95% CI 1.02-55.7, p = 0.05), and clinical vasospasm (OR 43.4, 95% CI 13.1-143.4, p < 0.01) were independently associated with the development of DCI. Diagnosis of nosocomial infection preceded the diagnosis of DCI in 15 (71.4%) of 21 patients. Patients diagnosed with nosocomial infection experienced significantly worse outcomes as measured by the modified Rankin Scale score at discharge and 1 year (p < 0.01 and p = 0.03, respectively). CONCLUSIONS Nosocomial infection is independently associated with DCI. This association is hypothesized to be partly causative through the exacerbation of systemic inflammation leading to thrombosis and subsequent ischemia. PMID- 26871204 TI - Involvement of circulating endothelial progenitor cells in carotid plaque growth and vulnerability. AB - OBJECTIVE The roles of endothelial progenitor cells (EPCs) in the development of carotid plaque are still obscure. This study aimed to clarify this by assessing the histological findings of specimens obtained from carotid endarterectomy. METHODS This study included 34 patients who underwent carotid endarterectomy. MR imaging was performed to semiquantitatively analyze the components of the carotid plaques in all patients. The surgical specimens were subjected to immunohistochemistry. The distributions of the CD34-, CD133-, VEGF-2R-positive cells in the carotid plaques were precisely analyzed, and their number was quantified. Simultaneously, the CD34-positive microvessels were localized. RESULTS The plaque component was judged as lipid-rich plaque in 19 patients, intraplaque hemorrhage (IPH) in 11 patients, and fibrous plaque in 4 patients. The CD34-positive microvessels were densely distributed in the plaque shoulder and interface-to-media regions. The CD34-, CD133-, and VEGF-2R-positive cells were mainly localized around the CD34-positive microvessels. The number of CD34 positive microvessels significantly correlated with the number of CD34-, CD133-, and VEGF-2R-positive cells (R = 0.308, p = 0.009; R = 0.324, p = 0.006; and R = 0.296, p = 0.013, respectively). Vulnerable plaques (lipid-rich and IPH) had significantly higher numbers of the CD34-positive microvessels (p = 0.007) and CD34-, CD133-, and VEGF-2R-positive cells than fibrous plaques (p = 0.031, p = 0.013, and p = 0.002). CONCLUSIONS These findings strongly suggest that neovascularization in the plaque shoulder and interface-to-media regions may play a key role in delivering EPCs from the peripheral blood to the carotid plaque, promoting the growth of carotid plaque. Furthermore, the invaded EPCs, especially the CD133-positive immature EPCs, may be related to plaque vulnerability. PMID- 26871205 TI - Borderline basal ganglia hemorrhage volume: patient selection for good clinical outcome after stereotactic catheter drainage. AB - OBJECTIVE The purpose of this study was to determine predisposing factors for good clinical outcome in patients with spontaneous basal ganglia hemorrhage with borderline volumes (defined as a hematoma volume between 20 and 50 cm3) who had undergone treatment by stereotactic catheter drainage. METHODS From the 298 patients whose information had been prospectively collected in the institutional database between January 2010 and December 2013, 93 patients were included in this retrospective study and divided into 2 groups: best medical treatment alone (Group A, n = 44) and best medical treatment plus catheterization (Group B, n = 49). All patients met the following criteria: 1) a diagnosis of spontaneous basal ganglia hemorrhage, and 2) a borderline hematoma volume (20 to 50 cm3). Postoperative modified Rankin Scale (mRS) scores and recovery of motor weakness were compared between the 2 groups, and predisposing factors for good clinical outcome were evaluated. RESULTS Patients in Group B showed earlier recovery of motor weakness and improved mRS scores than patients in Group A. The final mRS score at 12 months was better in Group B than in Group A (p = 0.006). Predisposing factors for a good clinical outcome were a hematoma volume < 30 cm3 (OR 6.158, 95% CI 1.221-31.053, p = 0.028), an initial Glasgow Coma Scale (GCS) score >= 13 (OR 6.331, 95% CI 1.129-35.507, p = 0.036), the absence of internal capsule involvement (OR 4.680, 95% CI 1.152-19.010, p = 0.031), and catheterization (OR 13.376, 95% CI 2.423-73.842, p = 0.003) based on logistic regression analysis. CONCLUSIONS Good clinical outcome can be expected after stereotactic catheter drainage in patients with a hematoma volume between 20 and 30 cm3, an initial GCS score >= 13, and the absence of internal capsule involvement. Among these patients, stereotactic catheter drainage may have a beneficial effect on early recovery of motor weakness and functional outcome, indicating that lateral-type basal ganglia hematoma compression not involving the internal capsule may be better treated using stereotactic catheter drainage than treated medically. PMID- 26871206 TI - Aneurysm remnant after clipping: the risks and consequences. AB - OBJECTIVE The complete clipping of a cerebral aneurysm usually warrants its sustained occlusion, while clip remnants may have far-reaching consequences. The aim of this study is to identify the risk factors for clip remnants requiring retreatment and/or exhibiting growth. METHODS All consecutive patients with primary aneurysm clipping performed at University Hospital of Essen between January 1, 2003, and December 31, 2013, were eligible for this study. Aneurysm occlusion was judged on obligatory postoperative digital subtraction angiography and the need for repeated vascular control. The identified clip remnants were correlated with various demographic and clinical characteristics of the patients, aneurysm features, and surgery-related aspects. RESULTS Of 616 primarily clipped aneurysms, postoperative angiography revealed 112 aneurysms (18%) with clip remnants requiring further control (n = 91) or direct retreatment (n = 21). Seven remnants exhibited growth during follow-up, whereas 2 cases were associated with aneurysmal bleeding. Therefore, a total of 28 aneurysms (4.5%) were retreated as clip remnants (range 1 day to 67 months after clipping). In the multivariate analysis, the need for retreatment of clip remnant was correlated with the aneurysm's initial size (> 12 mm; OR 3.22; p = 0.035) and location (anterior cerebral artery > internal carotid artery > posterior circulation > middle cerebral artery; OR 1.85; p = 0.003). Younger age with a cutoff at 45 years (OR 33.31; p = 0.004) was the only independent predictor for remnant growth. CONCLUSIONS The size and location of the aneurysm are the main risk factors for clip remnants requiring retreatment. Because of the risk for growth, younger individuals (< 45 years old) with clip remnants require a long-term (> 5 years) vascular follow-up. Clinical trial registration no: DRKS00008749 (Deutsches Register Klinischer Studien). PMID- 26871207 TI - Transcranial magnetic resonance-guided focused ultrasound for temporal lobe epilepsy: a laboratory feasibility study. AB - OBJECTIVE In appropriate candidates, the treatment of medication-refractory mesial temporal lobe epilepsy (MTLE) is primarily surgical. Traditional anterior temporal lobectomy yields seizure-free rates of 60%-70% and possibly higher. The field of magnetic resonance-guided focused ultrasound (MRgFUS) is an evolving field in neurosurgery. There is potential to treat MTLE with MRgFUS; however, it has appeared that the temporal lobe structures were beyond the existing treatment envelope of currently available clinical systems. The purpose of this study was to determine whether lesional temperatures can be achieved in the target tissue and to assess potential safety concerns. METHODS Cadaveric skulls with tissue mimicking gels were used as phantom targets. An ablative volume was then mapped out for a "virtual temporal lobectomy." These data were then used to create a target volume on the InSightec ExAblate Neuro system. The target was the amygdala, uncus, anterior 20 mm of hippocampus, and adjacent parahippocampal gyrus. This volume was approximately 5cm3. Thermocouples were placed on critical skull base structures to monitor skull base heating. RESULTS Adequate focusing of the ultrasound energy was possible in the temporal lobe structures. Using clinically relevant ultrasound parameters (power 900 W, duration 10 sec, frequency 650 kHz), ablative temperatures were not achieved (maximum temperature 46.1 degrees C). Increasing sonication duration to 30 sec demonstrated lesional temperatures in the mesial temporal lobe structures of interest (up to 60.5 degrees C). Heating of the skull base of up to 24.7 degrees C occurred with 30 sec sonications. CONCLUSIONS MRgFUS thermal ablation of the mesial temporal lobe structures relevant in temporal lobe epilepsy is feasible in a laboratory model. Longer sonications were required to achieve temperatures that would create permanent lesions in brain tissue. Heating of the skull base occurred with longer sonications. Blocking algorithms would be required to restrict ultrasound beams causing skull base heating. In the future, MRgFUS may present a minimally invasive, non-ionizing treatment of MTLE. PMID- 26871208 TI - The anconeus epitrochlearis muscle may protect against the development of cubital tunnel syndrome: a preliminary study. AB - OBJECTIVE The authors hypothesized that when the anatomical variant of an anconeus epitrochlearis is present, the risk of developing cubital tunnel syndrome would be reduced by replacing the normal roof of the cubital tunnel (Osborne's ligament) with a more forgiving muscular structure, the anconeus epitrochlearis. The authors further hypothesized that when the presence of an anconeus epitrochlearis contributes to ulnar neuropathy, it would be secondary to muscular hypertrophy, thereby making it more likely to occur in the dominant arm. Therefore, the goal of the present study was to evaluate these hypotheses. METHODS This retrospective cohort study was performed by reviewing the records of all adult patients who underwent operative intervention for cubital tunnel syndrome between 2005 and 2014 as the experimental group and all asymptomatic patients in the medical literature who were part of a series reporting the prevalence of an anconeus epitrochlearis as the control group. The primary outcome of interest was the presence of an anconeus epitrochlearis in asymptomatic individuals versus patients with cubital tunnel syndrome. RESULTS During the study period, 168 patients underwent decompression of the ulnar nerve for cubital tunnel syndrome, and an anconeus epitrochlearis was found at surgery in 9 (5.4%) patients. The control group consisted of 634 asymptomatic patients from the medical literature, and an anconeus epitrochlearis was present in 98 (15.5%) of these patients. An anconeus epitrochlearis was present significantly less frequently in the symptomatic patients than in asymptomatic individuals (p < 0.001). Among patients undergoing surgical decompression, an anconeus epitrochlearis was associated with symptoms in the dominant arm (p = 0.037). CONCLUSIONS The authors found that an anconeus epitrochlearis was present significantly less often in patients with cubital tunnel syndrome than in asymptomatic controls. The mechanism of protection may be that this muscle decreases the rigidity of the entrance into the cubital tunnel. When an anconeus epitrochlearis does contribute to cubital tunnel syndrome, it is significantly more likely to occur in the dominant arm, possibly due to repetitive use and hypertrophy of the anconeus epitrochlearis. The presence of an anconeus epitrochlearis may be protective against the development of cubital tunnel syndrome, although this is a preliminary finding. PMID- 26871209 TI - The challenge of the 67th Brazilian Conference of Nursing: In what direction is the Brazilian Nursing going? PMID- 26871210 TI - Nursing education: training evaluation by graduates, employers and teachers. AB - OBJECTIVE: to support the assessment and the necessary changes in the curriculum of an undergraduate degree in Nursing. METHODS: it is a descriptive study developed in two stages as an action research. In the first stage, the speeches of 19 graduates and 15 employers were interviewed and analyzed; in the second stage, five teachers participated in the focus group. For processing the data, the content analysis was adopted. RESULTS: based on the assessment of the actors, an action plan was created with suggestions regarding the curriculum flexibility, content resizing, continuing education, practice enhancement, active methodologies and autonomy of the student. CONCLUSION: the participation of actors participants of the training process and performance of professional nurses in the evaluation of a curriculum pointed aspects to realignment and provided concrete benefits to improving the quality of undergraduate course curriculum, scenario of this study. PMID- 26871211 TI - Evaluation of environmentally sustainable actions in the medication process. AB - OBJECTIVE: to analyze sustainable actions from an environmental point of view in the medication process, from the reception of the prescription of the pharmacy to waste discard by nursing. METHOD: study before and after performed through Lean Six Sigma methodology. The sample consisted of the amount and type of waste resulting from the pharmacy and nursing services of a medical-surgical clinical unit. RESULTS: after the intervention was obtained at the pharmacy a reduction of 74.8% of chemical, infectious and sharps waste, an increase of 33.3% of common recyclable and 20% of common non-recyclable. In nursing, there was a reduction of 22.5% of chemical, infectious and sharps waste, an increase of 22.9% of common recyclable and an increase of 20% of common non-recyclable. CONCLUSION: the practice of sustainable actions in the hospital is possible, contributing to the optimization of resources and waste production with benefits to the institution, environment, and health. PMID- 26871212 TI - Health indicators of workers of the hospital area. AB - OBJECTIVE: to analyze the health indicators of workers of hospital area for exposure to workloads, wear processes and its consequences. METHOD: a retrospective, descriptive and exploratory study performed in a hospital in southern Brazil. The population consisted of 1,050 workers notifications of registered in the Monitoring System of Nursing Workers Health, in 2011. RESULTS: 80.8% of the records were female workers, with 34.2% aged between 31 to 40 years old, corresponding to 2478 working lost days. The results subsidized the implementation of nine indicators that showed the prevalence of respiratory and osteoarticular problems. CONCLUSION: the results allow the reflection and redirection of actions for workers' health, as the processes of becoming ill are compounded by exposure to psychic burdens. These indicators, when monitored, can contribute to the transformation of the profile of morbidity of these workers. PMID- 26871213 TI - Influence of sociodemographic and clinical characteristics at the impact of valvular heart disease. AB - OBJECTIVE: to analyze the sociodemographic and clinical characteristics of patients with valvular heart disease and to verify the influence of these variables on the impact of valve disease in daily life. METHOD: the study involved 86 outpatients. Data collection was performed in two stages - face-to face interview for sociodemographic and clinical characterization and through telephone contact for the application of the Instrument to Measure the Impact of Valvular Heart Disease on Patient's Everyday Life (IDCV). Data were analyzed through descriptive statistics and multiple regression analysis. RESULTS: it was noticed that the total score of IDCV and its domains were influenced by age, schooling, presence or absence of symptoms, use or not of diuretic. CONCLUSION: The impact of the disease was influenced by sociodemographic and clinical variables. The results provide subsidies for the design of nursing interventions aimed at reducing the impact of the disease on the patient's daily life with valve disease. PMID- 26871214 TI - Factors associated with inconsistent condom use among people living with HIV/Aids. AB - OBJECTIVE: to analyze the prevalence and factors associated with inconsistent use of condoms among people living with HIV/ Aids (PLWHA). METHOD: it is a cross sectional study with 228, with individual interviews conducted in 2011. A multivariate analysis was performed with a logistic regression model. RESULTS: 143 participants met the inclusion criteria, and the prevalence of inconsistent condom use was 28.7%. However, there was greater adherence among men (79.3%). In the multivariate analysis, the independent variable daily use of alcohol (OR=11.02; 95% CI 1.84, 65.92; p = 0.021) was associated with inconsistent condom use. The chance of men making consistent condom use was higher than women (OR = 0.36, 95% CI 0.15, 0.81; p = 0.015). CONCLUSION: the prevalence of inconsistent condom male use among PLWHA was low, however, evidenced greater compliance among men over women with a statistically significant difference and the daily use of alcohol was associated with inconsistent condom use. PMID- 26871215 TI - Evaluating child care in the Family Health Strategy. AB - OBJECTIVE: to evaluate the healthcare provided to children under two years old by the Family Health Strategy. METHOD: evaluative, quantitative, cross-sectional study that used the Primary Care Assessment Tool - Child Version for measuring the access, longitudinality, coordination, integrality, family orientation and community orientation. RESULTS: a total of 586 adults responsible for children under two years old and linked to 33 health units in eleven municipalities of the state of Minas Gerais, Brazil, were interviewed. The evaluation was positive for the attributes longitudinality and coordination, and negative for access, integrality, Family orientation and community orientation. CONCLUSION: there are discrepancies between health needs of children and what is offered by the service; organizational barriers to access; absence of counter-reference; predominance of curative and long-standing and individual preventive practices; verticalization in organization of actions; and lack of good communication between professionals and users. PMID- 26871216 TI - Implementation of fast tests for syphilis and HIV in prenatal care in Fortaleza - Ceara. AB - OBJECTIVE: to describe the implementation of the Fast Test (FT) of syphilis and HIV in prenatal care in primary healthcare units in Fortaleza, Ceara. METHOD: a descriptive study with a quantitative approach. There were training supervisions carried out in 24 units between May and August 2014, and the inclusion criterion was to have at least one trained professional. RESULTS: the physical space, the availability, validity and the performance of FT in prenatal were analyzed. The data were presented in simple frequency tables. It was identified adequate space in 79.2% of the units, availability of FT in 62.5%, performing the tests in 37.5%, and of these, 55.6% doing these procedures in routine prenatal care. CONCLUSION: the primary units have difficulties in implementing FT in syphilis and HIV in the prenatal routine. This activity is seen as an effective strategy to reduce vertical transmission of these infections. PMID- 26871217 TI - Coping strategies for oncology nurses in high complexity. AB - OBJECTIVE: to identify the coping strategies of oncology services of nurses in highly complex hospital care before the person with cancer. METHOD: it is a qualitative research, with 18 nurses in inpatient oncology units and/or outpatient chemotherapy in two cities in southern Brazil, sampled by a snowball and carrying out semi-structured interviews. Data were submitted to thematic analysis. RESULTS: three categories emerged that show strategies such as denial and resignation in care, for support in the health team and the plurality and multiplicity of perspectives on the care, including the patient and his family and the search for personal and professional improvement. CONCLUSION: coping strategies are expressed in the cultural understanding of what it means to have cancer or not and management of health institutions for nurses to work with satisfaction. The service in education is a major factor in the development of ethical competence. PMID- 26871218 TI - Evaluation of quality of life of visually impaired. AB - OBJECTIVE: to evaluate the quality of life of visually impaired using WHOQOL-100. METHOD: exploratory, descriptive, and quantitative study, performed between April and May 2013 with 20 visually impaired of the Blind Association of Ceara, through interviews. RESULTS: the analysis showed that males predominated (80%), 41-55 years (40%), students (50%) and personal income than the minimum wage (70%). Participants were self-rated with good quality of life (68.75%). The facets with the highest rates were personal relationships (74.06%), sexual activity (66.88%) and spirituality/religion/personal beliefs (65%). With lower rates were financial (43.44%), physical environment: pollution/noise/traffic/climate (46.88%), physical security and protection (37.19%), transport (35.63%) and medication or treatment dependency (8.25%). CONCLUSION: these results reflect the importance of the nurse to perform health education actions promoting the empowerment, autonomy and guaranteed of access in society for this clientele. PMID- 26871219 TI - Evaluation of the care program implementation to people with high blood pressure. AB - OBJECTIVE: to evaluate the implementation of the care program for people with hypertension in Maringa-PR. METHOD: it is an evaluative research of cross sectional design. Data were collected through structured interviews with 63 nurses between April and June 2013. RESULTS: as missing or insufficient, there were: transportation for outside activities; work equipment; educational materials; training resources; inclusion of the family in the care plan; risk classification of individuals; determination of therapy from the risk classification and referral of the patient to medical and/or specialized tests. CONCLUSION: in addition to qualifying structure, there are: the need to identify people with hypertension as risk factors, perform risk stratification and systematic care planning, establishing an advanced clinical practice, such as support for self-care and management cases, accomplish with existing protocols and develop collective actions based on information systems. PMID- 26871220 TI - Children with special health needs and family: implications for Nursing. AB - OBJECTIVE: to understand the family experience of children and adolescents with myelomeningocele by the discovery of chronic illness and their daily life in the realization of needed care to these people. METHOD: qualitative study, developed from October 2013 to February 2014, with family, in a pediatric hospital in Fortaleza. Data were collected through interviews and checked by analysis thematic category. RESULTS: it was found that the diagnosis after the birth of the child caused fear and anguish to the families in front of the unknown and the unexpected and that over the years they started to deal with many challenges conducting the daily care due to the disease sequelae. CONCLUSION: nursing plays an important role in the lives of families, children and adolescents, through emotional support, guidelines and care inserted in the health care network. PMID- 26871221 TI - Assessment of the risk of pressure ulcer development among hospitalized HIV/Aids patients. AB - OBJECTIVE: to assess the risk of pressure ulcer development among hospitalized HIV/Aids. Metod: study quantitative descriptive with 35 patients admitted to an infectious diseases hospital in Curitiba-PR-BR. Characterized clinical and epidemiological of patients using a data collection instrument and the Braden Scale. Data was compiled using Excel(r) and a simple descriptive analysis. RESULTS: two patients were found to have pressure ulcers and the most common comorbidities associated with HIV/Aids were pneumocystis pneumonia, caused by pneumocisti cariini (16), and pulmonary tuberculosis (13). The lowest scores were obtained in the friction and shear subscale, followed by the activity, nutrition, mobility and moisture subscales. The highest score was obtained in the sensory perception subscale. Two patients were classified as 'very high risk', six as 'high risk', three as 'low risk', and the rest as 'no risk'. CONCLUSION: risk assessment using scales provides objective information to assist with systemized and targeted nursing decision-making. PMID- 26871222 TI - Defining characteristics of the nursing diagnosis "ineffective airway clearance". AB - OBJECTIVE: to analyze the defining characteristics of the nursing diagnosis "ineffective airway clearance" in children with acute respiratory infection. METHOD: cross-sectional descriptive study, developed in two hospitals specialized in care for children. It was held a detailed respiratory evaluation of the child to identify the defining characteristics of the diagnosis under study. RESULTS: a total of 249 children were evaluated, 55.8% were male and the median age was 13.76 months. Ineffective airway clearance was identified in 222 children (89.2%). The following defining characteristics presented statistically significant associations: dyspnea, expectoration, orthopnea, respiratory adventitious sounds, decreased breath sounds and ineffective cough. Decreased breath sounds, ineffective cough and respiratory adventitious sounds composed the logistic regression model. CONCLUSION: the characteristics decreased breath sounds, ineffective cough and respiratory adventitious sounds have better predictive capacity for the diagnosis "ineffective airway clearance" in children with acute respiratory infection. PMID- 26871223 TI - Significations of being the caregiver of the companion with cancer: an existential look. AB - OBJECTIVE: to unveil the significances of women who experience being the caregiver of their companion with cancer. METHOD: a Heidegger's phenomenological research, performed with ten women who are caregivers of their companions with cancer in a town in the northwest of the state of Parana, Brazil, from December 2013 to February 2014. The following guiding question was used: "How has it been for you to care for your companion with cancer?". RESULTS: from the analysis of the speeches the following ontological themes emerged: "Taking responsibility of caring for the companion with cancer", "Learning to live with the intimacy changes" and "Learning to live with the feelings related to care". The data revealed the wives' sense of responsibilities for caring and the influence of feelings in the act of caring, including the impact on the couple's intimacy. CONCLUSION: in the midst of difficulties, the feelings of affection are the driving force behind these women to continue their actions as wife-caregivers. PMID- 26871224 TI - Hospitalizations sensitive to primary health care at a regional hospital in the Federal District. AB - OBJECTIVE: to characterize hospitalizations for sensitive conditions to primary care of a regional hospital in the Federal District. METHOD: this is a descriptive study, such as case series that considered users admitted between 2008 and 2012 in the Regional Hospital of Ceilandia. The selection of hospitalizations was based on the Brazilian List, and the data were obtained from the Hospital information System. The descriptive statistics was used in the data processing and analysis. RESULTS: ACSC (Ambulatory Care Sensitive Conditions) showed a growth tendency, mainly due to cerebrovascular diseases, lung diseases and infections in the kidney and urinary tract. Female and elderly patients showed a higher frequency of hospitalizations. CONCLUSION: the results may help managers and health professionals to implement actions that aim higher solvability of primary care, and contribute to the systematization of nursing care and improved health care. PMID- 26871225 TI - Exposure and sun protection practices of university students. AB - OBJECTIVE: to learn exposure and sun protection practices for university students. METHOD: a descriptive, cross-sectional study performed at a university in Sao Paulo. RESULTS: the sample consisted of 385 young and data collection conducted through a form. Of the total, 239 (62%) young people were classified as skin type III and IV and 69 (17.9%) affirmed to have a history of skin cancer in the family. Most affirmed exposure to the sun between 10 a.m and 04 p.m and for more than one hour; 112 (29.1%) informed not employ safeguards. Among those who use sunscreen, the minority does so regularly. CONCLUSION: although the sample was made up of people with greater access to information, it was found exposure and sunscreen improperly. Education, individual and collective actions should be strengthened and prioritized given the incidence of skin cancer in the country. PMID- 26871226 TI - Quality of life and accession to the pharmacological treatment among elderly hypertensive. AB - OBJECTIVE: to compare variables obtained in adherence and non-adherence to drug treatment for hypertension, according to socioeconomic situation, time of diagnosis, self-reported morbidities, indicative of depression and quality of life. METHOD: cross-sectional analytical study of 524 elderly with adherence and 505 non-adherence to the treatment. A descriptive analysis, Chi-square test and Student t test (p < 0.05) were held. RESULTS: there was higher proportion of older subjects, indicative of morbidity and depression among those with adherence. Non-adherence subjects had lower scores in all domains and quality of life facets. CONCLUSION: actions favoring the adherence to pharmacological treatment should be recommended, to minimize the impact of comorbidities and improve quality of life. PMID- 26871227 TI - Clinical competences of nursing assistants: a strategy for people management. AB - OBJECTIVE: to identify the clinical competences of nursing assistants in a hospital organization and to understand how professional acquired these competences. METHOD: an exploratory study of a qualitative approach, performed at a private hospital in southern Brazil, through a semi-structured interview, in May and June 2013 with 20 nursing assistants. RESULTS: the nursing assistantswho worked longer in the same work unit had a higher list of clinical competences. The acquisition of clinical competences occurred through interaction with other professionals; in daily nursing practice; in previous experiences and in formal learning. FINAL CONSIDERATIONS: the identification of clinical competences and the way nursing assistants acquire these competences can be important resources for managing people, which can be used by nurse managers to better allocate these professionals and provide th e opportunity for their professional development. PMID- 26871228 TI - Profile of patients with brain tumors and the role of nursing care. AB - OBJECTIVE: to describe the profile of 200 patients with central nervous system tumors (CNST), and the role of the nursing care. METHOD: prospective, quantitative and descriptive analysis of medical records of 200 patients with TSNC. RESULTS: a total of 61% of our patients had benign CNST and 39% had malignant tumors. The extent of patient dependence, according to the Karnofsky Performance Status scale, was significantly greater for patients with malignant CNST (p < .05), indicating that these patients needed more support with their activities of daily living. CONCLUSION: patients with CNST need specialized care, with specific guidance regarding their disease and aspects of daily living after treatment. Thus, the nurse can function as a key element for the effectiveness of care provided to patients and family members with the aim of enhancing the quality of life of all those affected, directly or indirectly, by the disease. PMID- 26871229 TI - Conditions of functional health literacy of an elderly diabetics group. AB - OBJECTIVE: to evaluate the conditions of functional health literacy of an elderly diabetics group. METHOD: cross-sectional and descriptive study, with diabetic's elderly assisted in the SUS (N = 114). The social and health conditions were evaluated as well as functional health literacy by S-TOFHLA test (short version); the simple proportions, average, standard deviation and Pearson's Chi-square were described by SPSS software (20.0) with alpha = 5% value. RESULTS: the mean age was 67.4 years, 74.0% of the elderly were women, had up to four years of schooling; 29.8% had a long-standing illness, 64.0% reported having high blood pressure, 47.4% smoke or were smokers, 73.7% had low functional health literacy, which was associated with schooling p = 0.001. CONCLUSIONS: the low functional health literacy could be a self-care conditioning and can be influenced by low schooling because it implies to have skills to understand and make decisions aimed at self-management of health. PMID- 26871230 TI - Clinical indicators of sexual dysfunction in pregnant women: integrative literature review. AB - OBJECTIVE: to identify the nursing diagnosis clinical indicators of sexual dysfunction in pregnant women. METHOD: it is an integrative literature review, with research in databases using the keywords "sexual*", "pregnan*" and "function*". Studies included had an abstract available for analysis, referring to pregnant women over 18 years old, written in Portuguese, French, Spanish and English, with publication date between 2010 and 2014. Studies that reporting pregnant women with an associated pathology were excluded. RESULTS: sexual dysfunction in pregnant women is consistent in the literature. Nine defining characteristics were identified and 16 related factors, some not classified in NANDA International. CONCLUSION: clinical indicators can be added to the nursing diagnosis to favor an accurate diagnosis and effective interventions in the surveillance of pregnancy as a period of healthy sexual experience. PMID- 26871232 TI - Nurses' performance on primary care in the National Health Service in England. AB - OBJECTIVE: To analyze the expansion of nursing roles in primary care in the English National Health Service and the implications for professional practice. METHOD: qualitative research in case study format, held in London, England, in six primary care units. Data were obtained through interviews with nine nurses. After the thematic data analysis, two units emerged: the nurses' performance characteristics and effects of the expansion of nursing roles. RESULTS: expansion of nurses' roles: consultation, diagnosis and drug therapy, case management and monitoring of chronic conditions. Repercussions: for the user, there was improved access, communication and comprehensive care, increased duration of consultations, resulting in greater adherence; for nurses, there was the expansion of professional skills, knowledge and professional recognition; to the health care system, it resulted in cost savings. CONCLUSION: benefits in expanding nursing roles, were visible, contributing to primary care quality. PMID- 26871231 TI - Meleis' Nursing Theories Evaluation: integrative review. AB - OBJECTIVE: to analyze the application of the theory evaluation model proposed by Meleis in Brazilian studies. METHOD: integrative review of online articles published from 2002 to 2012 in the databases LILACS and BDENF. RESULTS: the 16 selected studies confirmed the use of only three of the five stages proposed for Meleis' theories analysis: Description of the Theory, Criticism of the Theory and Analysis of the Theory, with a predominance of a single unit of analysis in each. CONCLUSION: the analysis of nursing theories provides support to nurses in the practice, research, education and administration of the different dimensions of care. Meleis' model figures as very important by contributing to the development of knowledge of nursing discipline, considering that its use as a method allows several reflections on theories in order that they be revalidated to support a more theoretical and practical applicability. PMID- 26871233 TI - Qualitative methodologies in health research: interpretive referential of Patricia Benner. AB - OBJECTIVE: this article reports on the experience of using the interpretive phenomenological framework of Patricia Benner in a Brazilian context. Benner's interpretive phenomenology, based on existential and interpretative philosophy, aims to understand human experiences in the particular worlds of research participants. Data were collected through interviews with nine nurses in November and December 2014. RESULTS: data analysis process according to Benner's framework consisted of: transcription, coding, thematic analysis, and search for paradigmatic cases and examples. Therefore, the prior knowledge of the researcher is an important part of the study, consisting in manners of the research conduction. CONCLUSION: The use of this methodological framework entailed a great challenge for the researcher, however, it also enabled a unique opportunity to illuminate important existential phenomena related to the daily lives of research participants. PMID- 26871234 TI - Nursing process documentation: rationale and methods of analytical study. AB - OBJECTIVE: to describe the methods used to analyze the associations between variables of service, nursing and the nursing process documentation in institutions of the Department of Health of the State of Sao Paulo. METHOD: multilevel analytical study with data obtained in the domains of institution, units of the institution and nursing professionals who work there, using standardized instruments. The analyses had as axis the degree of completeness of the nursing process documentation in units or institutions and their association with variables of nursing personnel, of units and of institutions. CONCLUSION: This study will provide important empirical evidence on the factors involved in the nursing process documentation. PMID- 26871235 TI - ERRATUM. PMID- 26871236 TI - ERRATUM. PMID- 26871237 TI - Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus. AB - OBJECTIVE: CES1 encodes carboxylesterase-1, an important drug-metabolizing enzyme with high expression in the liver. Previous studies have reported a genomic translocation of the 5' region from the poorly expressed pseudogene CES1P1, to CES1, yielding the structural variant CES1VAR. The aim of this study was to characterize this translocation and its effect on CES1 expression in the human liver. MATERIALS AND METHODS: Experiments were conducted in human liver tissues and cell culture (HepG2). The promoter and exon 1 of CES1 were sequenced by Sanger and Ion Torrent sequencing to identify gene translocations. The effects of CES1 5'UTRs on mRNA and protein expression were assessed by quantitative real time PCR, allelic ratio mRNA analysis by primer extension (SNaPshot), quantitative targeted proteomics, and luciferase reporter gene assays. RESULTS: Sequencing of CES1 identified two translocations: first, CES1VAR (17% minor allele frequency) comprising the 5'UTR, exon 1, and part of intron 1. A second shorter translocation, CES1SVAR, was observed excluding exon 1 and intron 1 regions (<0.01% minor allele frequency). CES1VAR is associated with 2.6-fold decreased CES1 mRNA and ~1.35-fold lower allelic mRNA. Luciferase reporter constructs showed that CES1VAR decreases luciferase activity 1.5-fold, whereas CES1SVAR slightly increases activity. CES1VAR was not associated with CES1 protein expression or metabolism of the CES1 substrates enalapril, clopidogrel, or methylphenidate in the liver. CONCLUSION: The frequent translocation variant CES1VAR reduces mRNA expression of CES1 in the liver by ~30%, but protein expression and metabolizing activity in the liver were not detectably altered - possibly because of variable CES1 expression masking small allelic effects. Whether drug therapies are affected by CES1VAR will require further in-vivo studies. PMID- 26871239 TI - Progressive Motor Deficits and Psychosis After Stroke: A Case Presentation. PMID- 26871238 TI - Effects of Fentanyl and Morphine on Shivering During Spinal Anesthesia in Patients Undergoing Endovenous Ablation of Varicose Veins. AB - BACKGROUND We sought to investigate the effect of morphine and fentanyl on shivering when used adjunctively with bupivacaine during spinal anesthesia in patients undergoing varicose vein surgery on an outpatient basis. MATERIAL AND METHODS The study included a total of 90 patients, aged 25-45 years, ASA I-II, scheduled to undergo endovenous laser ablation under spinal anesthesia for lower extremity venous insufficiency/varicose vein disease. Patients were randomly allocated into 3 groups: Group M (morphine group) received 5 mg 0.5% hyperbaric bupivacaine + 0.1 mg morphine, Group F (fentanyl group) received 5 mg 0.5% hyperbaric bupivacaine + 25 ug fentanyl, and Group C (control group) received 5 mg 0.5% hyperbaric bupivacaine + physiologic saline. The level of sensory blockade was assessed with pin-prick test and the level of motor blockade was assessed with Bromage scale at 5-min intervals. Shivering grade and time to first postoperative analgesic requirement was recorded. RESULTS Level and time of sensory block showed a slight but insignificant increase in the Morphine Group and Fentanyl Group. Time of postoperative analgesic requirement was significantly longer in patients who received morphine (p<0.05). Shivering was significantly less common in patients who received morphine and fentanyl than in patients who are in the Control Group (p<0.02). CONCLUSIONS Morphine or fentanyl may be used as adjunctives to spinal anesthesia to prevent shivering in patients undergoing venous surgery. PMID- 26871240 TI - Cerebral Mycotic Aneurysm and Infective Endocarditis: A Case Study. AB - Neurologic complications occur in 20%-40% of patients with infective endocarditis. Mycotic aneurysms are one example of these complications, and although rare, they can confound a patient's recovery and increase morbidity and mortality. This article will examine one patient's experience and the devastating effects that this complication had on his life. The information in this article will help to support neurological nurses in refining care and facilitating the best possible recovery for patients who develop this condition. PMID- 26871241 TI - Nursing Roles and Functions in the Acute and Subacute Rehabilitation of Patients With Stroke: Going All In for the Patient. AB - BACKGROUND: The description of nursing roles and functions in rehabilitation of patients with stroke remains sparse. AIM: The aim of this study was to describe the experienced roles and functions of nurses during in-hospital rehabilitation of patients with stroke. METHODS: Within a phenomenological hermeneutic approach, 19 nurses working with in-hospital rehabilitation of patients with stroke participated in three focus group interviews during 2013. FINDINGS: The nurses' experiences were described in two themes: (a) the nurse's role and function in relation to the patient's needs 24/7 and (b) the nurse's role and function in the interdisciplinary team. Getting to know the patient as a person was essential to the nurses to care for the patient's basic needs; these must come first working with rehabilitation and always include the relatives. Recognition of the team members' individual skills with focus on the patient's needs must be the center of attention. CONCLUSION: An interdisciplinary rehabilitation program actively needs to include the patient by integrating the patient's perspective in the goals as well as in daily rehabilitation. In the team, nurses had the role of coordinator and the patient's voice. PMID- 26871243 TI - Preventing Cancer: Bad Luck or Lifestyle? PMID- 26871244 TI - Clinical Nurse Specialists' Perceptions of Care for Vulnerable Patients. AB - The vulnerable and underserved are populations that have higher risks in health care. A clinical nurse specialist is an advanced practice registered nurse who can help mitigate risks and provide holistic care for these patients. Researching clinical nurse specialists' perceptions of their role in caring for the vulnerable populations is important to ensuring quality care and filling in current practice weaknesses. PMID- 26871242 TI - Parent Perceptions of How Nurse Encounters Can Provide Caring Support for the Family in Early Acute Care After Children's Severe Traumatic Brain Injury. AB - OBJECTIVE: A child's severe traumatic brain injury (TBI) creates a family crisis requiring extensive cultural, informational, psychological, and environmental support. Nurses need to understand parents' expectations of caring in early acute care so they can tailor their attitudes, beliefs, and behaviors appropriately to accommodate the family's needs. METHODS: In a previous qualitative study of 42 parents or caregivers from 37 families of children with moderate-to-severe TBI, parents of children with severe TBI (n = 25) described their appraisals of nurse caring and uncaring behaviors in early acute care. Swanson's theory of caring was used to categorize parents' descriptions to inform nursing early acute care practices and family-centered care. RESULTS: Caring nurse encounters included (a) involving parents in the care of their child and reflecting on all sociocultural factors shaping family resources and responses (knowing); (b) respecting that family grief can be co-mingled with resilience and that parents are typically competent to be involved in decision making (maintaining belief); (d) actively listening and engaging parents to fully understand family values and needs (being with); (e) decreasing parents' workload to get information and emotional support and provide a safe cultural, psychological, and physical environment for the family (doing for); and (f) providing anticipatory guidance to navigate the early acute care system and giving assistance to learn and adjust to their situation (enabling). CONCLUSION: Application of Swanson's caring theory is prescriptive in helping individual nurses and early acute care systems to meet important family needs after children's severe TBI. PMID- 26871245 TI - Does Telephone Follow-Up and Education Affect Self-Care and Metabolic Control in Diabetic Patients? AB - The major goal of diabetes control is to assist patients to perform self-care and metabolic control. One possible way to achieve this goal is education and regular monitoring of patients by telephone. Thus, the present study was conducted with the aim of investigating the impact of education and telephone follow-up on self care and metabolic control in diabetic patients. This experimental study was conducted at a hospital in the Central Anatolia region of Turkey, with 88 diabetic patients including 44 intervention subjects and 44 control subjects. After an initial discussion, patients in the intervention group received education and telephone follow-up for 3 months. Required approvals were obtained before initiation of the study. Data were collected using a questionnaire form and the Diabetes Self-Care Scale. The Diabetes Self-Care Scale scores ranged between 140 and 210, where higher scores indicated increased self-care activities of patients. At the end of the study, the self-care score was found to increase from 61.3 +/- 10.9 to 89.9 +/- 12.3 in the intervention group (P < .005), but it showed a reduction from 56.5 +/- 7.6 to 54.7 +/- 9.3 after 3-month period in the control group. Education and telephone follow-up was also found to reduce the values of several variables of metabolic control including hemoglobin A1c, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and systolic blood pressure. In conclusion, education and telephone follow-up of diabetic patients led to increased self-care scores and had a positive impact on metabolic control variables. In light of these findings, we suggest that education and tele health home monitoring may be provided on a continuous basis to help patients sustain self-care behaviors that they have adopted during the study period. PMID- 26871246 TI - Amish Culture and Their Utilization of Burns and Wounds Ointment for the Treatment of Burns. AB - As indicated in the 2010 United States Religion Census, there are approximately 251,000 Amish people in the United States and Ontario. This census also demonstrated that a new Amish community is founded on average about every three and-a-half weeks, suggesting that this religious culture is the fastest-growing religion throughout the United States. Because of the rapid growth of the Amish population, it is essential for health care workers to understand their background, cultural, and health care beliefs, especially in the treatment of burns. The purpose of this article is to examine the Amish background, cultural, and health care beliefs, specifically the utilization of burns and wounds ointment and burdock leaves in the treatment of burns. PMID- 26871247 TI - Engel's Model as a Conceptual Framework in Nursing Research: Well-being and Disability of Patients With Migraine. AB - Exploring, selecting, and utilizing an appropriate conceptual framework is a vital step in development of a research work. This article discusses the application of "Engel's model on biopsychosocial well-being," in exploring the relationship between biopsychosocial well-being and disability of patients with migraine headaches. PMID- 26871248 TI - A Randomized Controlled Trial of Listening to Recorded Music for Heart Failure Patients: Study Protocol. AB - AIMS: To describe a conceptual framework and to test the effectiveness of a recorded music-listening protocol on symptom burden and quality of life in heart failure (HF) patients. BACKGROUND: Heart failure is an important public health problem. Many HF patients experience symptoms burden and poor quality of life, even with current improvements in pharmacological treatments. Recorded music listening has been shown to improve outcomes in cardiovascular patients, but it has never been tested on HF patients and with a specific music protocol and a randomized controlled trial methodology. METHODS: This study is a multicenter blinded randomized controlled trial that will involve 150 patients. Eligible patients will have a diagnosis of HF, in New York Heart Association functional classification of I to III, and will be recruited from 3 large hospitals in Northern Italy. Patients will be randomly allocated in a 1:1 ratio to receive recorded music-listening intervention with or without standard care for 3 months. Data will be collected at baseline and at the end of the first, second, and third month during the intervention, and at 6 months for follow-up. The following variables will be collected from HF patients with validated protocols: quality of life (primary endpoint), use of emergency services, rehospitalization rates, all cause mortality, self-care, somatic symptoms, quality of sleep, anxiety and depression symptoms, and cognitive function. DISCUSSION: This study will examine the effect of recorded music listening on HF patients and will inform clinical practice. If the findings are found to be positive, the protocol could be used as a tool for evidence-based applications of recorded music in HF patients. The framework developed in this study may be helpful for future research focused on the effects of music in HF patients. PMID- 26871249 TI - Successful Fecal Bacteria Transplantation and Nurse Management for a Patient With Intractable Functional Constipation: A Case Study. AB - Intractable functional constipation is a common gastrointestinal disorder that features persistent difficult defecation, reduced bowel movements, or a feeling of incomplete defecation. Despite many therapeutic approaches, there has not been an established standard treatment protocol. Fecal microbiota transplantation (FMT), an innovative therapy that was introduced recently, has been preliminarily shown to have good effects and is expected to have good prospects. However, nursing is also of great importance during the process of FMT. An innovative nursing care protocol is combined with FMT, with a view to improving the clinical symptoms and quality of life of patients with intractable functional dyspepsia. This case-based study addresses the effects of nursing interventions used during the treatment of one patient with intractable functional constipation who received FMT. PMID- 26871250 TI - Echinacea Formula (Echinaforce(r) Hotdrink): Effects of a Proprietary Echinacea Formula Compared With Oseltamivir in the Early Treatment of Influenza. PMID- 26871251 TI - Supplement Nonchalance Influenced by Supplement Naivete. PMID- 26871252 TI - Extracellular matrix proteins in the regulation of thrombus formation. AB - PURPOSE OF REVIEW: Exposure of subendothelial extracellular matrix (ECM) proteins to the circulation is the key event that initiates platelet accumulation and clot formation after vessel injury. Soluble ECM proteins are also essential for support and regulation of these events. This review discusses the current understanding of ECM proteins in thrombosis and hemostasis. RECENT FINDINGS: Fibrinogen and von Willebrand factor (VWF) are considered essential for thrombosis and hemostasis. Interestingly, alphaIIbbeta3 integrin-dependent thrombus formation persists in the absence of fibrinogen and VWF, suggesting that other alphaIIbbeta3 ligand (s), likely ECM proteins, can still mediate thrombosis. Fibronectin increases in platelets of fibrinogen-deficient humans and mice. This ECM protein can rapidly deposit onto the injured vessel wall prior to platelet accumulation. By switching from the soluble to insoluble form, plasma fibronectin supports hemostasis and inhibits excessive thrombosis. Fibrin, fibronectin, VWF, vitronectin, neutrophil extracellular traps, and other ECM proteins in the blood clot form a de-facto ECM, which interacts with various types of blood cells to regulate the evolution and resolution of the clot. SUMMARY: ECM proteins are intricately involved in major steps of thrombus formation. Further investigations of ECM proteins will reveal new therapeutic targets for treatment of thrombosis and bleeding disorders. VIDEO ABSTRACT: http://links.lww.com/COH/A12 PMID- 26871253 TI - Metabolic regulation of hematopoietic stem cell commitment and erythroid differentiation. AB - PURPOSE OF REVIEW: Hematopoietic stem cell (HSC) renewal and lineage differentiation are finely tuned processes, regulated by cytokines, transcription factors and cell-cell contacts. However, recent studies have shown that fuel utilization also conditions HSC fate. This review focuses on our current understanding of the metabolic pathways that govern HSC self-renewal, commitment and specification to the erythroid lineage. RECENT FINDINGS: HSCs reside in a hypoxic bone marrow niche that favors anaerobic glycolysis. Although this metabolic pathway is required for stem cell maintenance, other pathways also play critical roles. Fatty acid oxidation preserves HSC self-renewal by promoting asymmetric division, whereas oxidative phosphorylation induces lineage commitment. Committed erythroid progenitors support the production of 2.4 million erythrocytes per second in human adults via a synchronized regulation of iron, amino acid and glucose metabolism. Iron is indispensable for heme biosynthesis in erythroblasts; a process finely coordinated by at least two hormones, hepcidin and erythroferrone, together with multiple cell surface iron transporters. Furthermore, hemoglobin production is promoted by amino acid-induced mTOR signaling. Erythropoiesis is also strictly dependent on glutamine metabolism; under conditions where glutaminolysis is inhibited, erythropoietin-signaled progenitors are diverted to a myelomonocytic fate. Indeed, the utilization of both glutamine and glucose in de-novo nucleotide biosynthesis is a sine qua non for erythroid differentiation. SUMMARY: Diverse metabolic networks function in concert with transcriptional, translational and epigenetic programs to regulate HSC potential and orient physiological as well as pathological erythroid differentiation. PMID- 26871255 TI - Single donor electronics and quantum functionalities with advanced CMOS technology. AB - Recent progresses in quantum dots technology allow fundamental studies of single donors in various semiconductor nanostructures. For the prospect of applications figures of merits such as scalability, tunability, and operation at relatively large temperature are of prime importance. Beyond the case of actual dopant atoms in a host crystal, similar arguments hold for small enough quantum dots which behave as artificial atoms, for instance for single spin control and manipulation. In this context, this experimental review focuses on the silicon-on insulator devices produced within microelectronics facilities with only very minor modifications to the current industrial CMOS process and tools. This is required for scalability and enabled by shallow trench or mesa isolation. It also paves the way for real integration with conventional circuits, as illustrated by a nanoscale device coupled to a CMOS circuit producing a radio-frequency drive on chip. At the device level we emphasize the central role of electrostatics in etched silicon nanowire transistors, which allows to understand the characteristics in the full range from zero to room temperature. PMID- 26871254 TI - Usefulness of Flow Cytometric Mepacrine Uptake/Release Combined with CD63 Assay in Diagnosis of Patients with Suspected Platelet Dense Granule Disorder. AB - Dense granule disorder is one of the most common platelet abnormalities, resulting from dense granule deficiency or secretion defect. This study was aimed to evaluate the clinical usefulness of the flow cytometric combination of mepacrine uptake/release assay and CD63 expression detection in the management of patients with suspected dense granule disorder. Over a period of 5 years, patients with abnormal platelet aggregation and/or reduced adenosine triphosphate (ATP) secretion suggestive of dense granule disorder were consecutively enrolled. The flow cytometric assays were systematically performed to further investigate dense granule functionality. Among the 26 included patients, 18 cases showed impaired mepacrine uptake/release and reduced CD63 expression on activated platelets, consistent with delta-storage pool deficiency (SPD). Another seven patients showed decrease in mepacrine release and CD63 expression but mepacrine uptake was normal, indicating secretion defect rather than delta-SPD. Unfortunately, ATP secretion could not be measured in 7 out of the 26 patients due to insufficient sample and/or severe thrombocytopenia. This test combination provides a rapid and effective method to detect the heterogeneous abnormalities of platelet dense granule by distinguishing between storage and release defects. This combination is particularly advantageous for severely thrombocytopenic patients and pediatric patients in which only minimal sample is required. PMID- 26871256 TI - Spectroscopy and control of near-surface defects in conductive thin film ZnO. AB - The electronic structure of inorganic semiconductor interfaces functionalized with extended pi-conjugated organic molecules can be strongly influenced by localized gap states or point defects, often present at low concentrations and hard to identify spectroscopically. At the same time, in transparent conductive oxides such as ZnO, the presence of these gap states conveys the desirable high conductivity necessary for function as electron-selective interlayer or electron collection electrode in organic optoelectronic devices. Here, we report on the direct spectroscopic detection of a donor state within the band gap of highly conductive zinc oxide by two-photon photoemission spectroscopy. We show that adsorption of the prototypical organic acceptor C60 quenches this state by ground state charge transfer, with immediate consequences on the interfacial energy level alignment. Comparison with computational results suggests the identity of the gap state as a near-surface-confined oxygen vacancy. PMID- 26871257 TI - Towards promising modification of GeSi nanostructures via self-assembly on miscut Si(001) substrates. AB - Self-assembled GeSi nanostructures on miscut Si(001) substrates are studied systematically with regard to the miscut angle and azimuth, the amount of Ge and the growth temperature. The comprehensive dependence of the spatial arrangement, which can exhibit one- and two-dimensional (1D and 2D) ordering, as well as the shape and density, of GeSi nanostructures on the miscut angle is observed. The orientation and side-walls of the 1D ordered in-plane GeSi nanowires on miscut Si(001) substrates are intimately associated with the miscut azimuth towards the <110> or <010> directions. Furthermore, the unique evolution of the GeSi nanostructures with the amount of Ge and the growth temperature on miscut Si (001) substrates towards the <010> direction is discovered. Such promising features of self-assembled GeSi nanostructures on miscut Si (001) substrates are explained in terms of the thermodynamics and growth kinetics, which are both affected significantly by the substrate vicinality. These results demonstrate that the miscut substrates offer a promising degree of freedom for the feasible modification of self-assembled nanostructures. PMID- 26871259 TI - Increase of interleukin-10-producing B cells associated with long-term remission after i.v. immunoglobulin treatment for pemphigus. AB - We present a refractory case of pemphigus vulgaris that achieved long-term remission after i.v. immunoglobulin treatment (IVIG). We evaluated the fluctuation of circulating interleukin-10-producing B cells (B10 cells) during the course in our case and other three patients with pemphigus treated with IVIG without clinical remission. B10 cells were observed predominantly in CD1d(-) , CD5(-) , CD9(-) and CD27(+) populations among CD19(+) cells in healthy controls, as well as in patients with pemphigus. The frequency of B10 cells among CD19(+) cells increased in our case, but not in the other three patients without clinical remission, which leads to speculation on the association between the increase of B10 cells and the achievement of long-term remission after IVIG treatment. PMID- 26871258 TI - Studying the features of 57 confirmed CRISPR loci in 29 strains of Escherichia coli. AB - Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) system is a novel type of innate defense system in prokaryotes for destruction of exogenous elements. To gain further insight into behavior and organization of the system, the extensive analysis of the available sequenced genomes is necessary. The dynamic nature of CRISPR loci is possibly valuable for typing and relative analyses of strains and microbial population. There are a few orderly bioinformatics investigations about the structure of CRISPR sequences in the Escherichia coli strains. In this study, 57 CRISPR loci were selected from 32 Escherichia coli strains to investigate their structural characteristics and potential functions using bioinformatics tools. Our results showed that most strains contained several loci that mainly included conserved direct repeats, while the spacers were highly variable. Moreover, RNA analysis of the sequences indicated that all loci could form stable RNA secondary structures and showed homology mostly with phages compared to plasmids. Only three strains included cas genes around their loci. PMID- 26871260 TI - Investigation and modeling of the effects of light spectrum and incident angle on the growth of Chlorella vulgaris in photobioreactors. AB - An in-depth investigation of how various illumination conditions influence microalgal growth in photobioreactors (PBR) has been presented. Effects of both the light emission spectrum (white and red) and the light incident angle (0 degrees and 60 degrees ) on the PBR surface were investigated. The experiments were conducted in two fully controlled lab-scale PBRs, a torus PBR and a thin flat-panel PBR for high cell density culture. The results obtained in the torus PBR were used to build the kinetic growth model of Chlorella vulgaris taken as a model species. The PBR model was then applied to the thin flat-panel PBR, which was run with various illumination conditions. Its detailed representation of local rate of photon absorption under various conditions (spectral calculation of light attenuation, incident angle influence) enabled the model to take into account all the tested conditions with no further adjustment. This allowed a detailed investigation of the coupling between radiation field and photosynthetic growth. Effects of all the radiation conditions together with pigment acclimation, which was found to be relevant, were investigated in depth. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:247-261, 2016. PMID- 26871261 TI - Does inflammation induced by ultraviolet B and heat rekindling alter pain-related behaviour in rats? AB - OBJECTIVE: To investigate whether induction of the ultraviolet B and heat rekindling (UVB/HR) model alters burrowing behaviour in rats. STUDY DESIGN: Randomized, blinded, prospective experimental study. ANIMALS: Sixteen adult male Wistar rats weighing 250-300 g. METHODS: In the UVB/HR group (n = 8), UV irradiation was delivered to the heel area of the right plantar pelvic limb paw at a dose of 1000 mJ cm(-2) , using a narrow-band UVB light source. Twenty-four hours later, heat rekindling was performed by placement of a feedback-controlled thermode set at a constant temperature of 45 degrees C over the area of UVB irradiation for 5 minutes. Both interventions were carried out under pentobarbital anaesthesia. The 'sham' group (n = 8) was anaesthetized only. In the burrowing test, rats were housed singly for 2 hours in cages furnished with a burrow filled with sand. The amount of sand remaining in the burrow after 2 hours was weighed and the amount displaced from the burrow calculated. The burrowing test was carried out for two consecutive days prior to UVB irradiation (day 0), on day 1 prior to HR, on days 2 and 3 after UVB exposure and at equivalent time points in the sham group. RESULTS: Rats in the sham group burrowed means (SD) of 2429 (73) g and 2358 (124) g of sand on days -2 and 3, respectively, while those in the UVB/HR group burrowed 2460 (26) and 2419 (58) g on days -2 and 3, respectively. There was no significant effect of treatment on the amount of sand burrowed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Pain associated with UVB/HR model induction is below the threshold required to affect rat burrowing behaviour and therefore questions the face validity of UVB/HR as a translational model of inflammatory pain. PMID- 26871262 TI - The use of public health e-learning resources by pharmacists in Wales: a quantitative evaluation. AB - OBJECTIVE: The aim of this study was to examine how communicable disease e learning resources were utilised by pharmacy professionals and to identify whether uptake of the resources was influenced by disease outbreaks. METHOD: Retrospective analysis of routine data regarding the number of individuals completing e-learning resources and statutory notifications of communicable disease. RESULTS: A high proportion of pharmacy professionals in Wales (38.8%, n = 915/2357) accessed the resources; around one in six completed multiple resources (n = 156). The most commonly accessed were those where there had been a disease outbreak during the study period. There was a strong positive correlation between e-learning uptake and number of disease cases; this was observed both for measles and scarlet fever. CONCLUSIONS: Communicable disease e-learning appears to be an acceptable method for providing communicable disease information to pharmacy professionals. Study findings suggest that e-learning uptake is positively influenced by disease outbreaks this reflects well both on pharmacy professionals and on the e-learning resources themselves. PMID- 26871263 TI - Diffusion tensor imaging of the human kidney: Does image registration permit scanning without respiratory triggering? AB - PURPOSE: To investigate if image registration of diffusion tensor imaging (DTI) allows omitting respiratory triggering for both transplanted and native kidneys MATERIALS AND METHODS: Nine kidney transplant recipients and eight healthy volunteers underwent renal DTI on a 3T scanner with and without respiratory triggering. DTI images were registered using a multimodal nonrigid registration algorithm. Apparent diffusion coefficient (ADC), the contribution of perfusion (FP ), and the fractional anisotropy (FA) were determined. Relative root mean square errors (RMSE) of the fitting and the standard deviations of the derived parameters within the regions of interest (SDROI ) were evaluated as quality criteria. RESULTS: Registration significantly reduced RMSE in all DTI-derived parameters of triggered and nontriggered measurements in cortex and medulla of both transplanted and native kidneys (P < 0.05 for all). In addition, SDROI values were lower with registration for all 16 parameters in transplanted kidneys (14 of 16 SDROI values were significantly reduced, P < 0.04) and for 15 of 16 parameters in native kidneys (9 of 16 SDROI values were significantly reduced, P < 0.05). Comparing triggered versus nontriggered DTI in transplanted kidneys revealed no significant difference for RMSE (P > 0.14) and for SDROI (P > 0.13) of all parameters. In contrast, in native kidneys relative RMSE from triggered scans were significantly lower than those from nontriggered scans (P < 0.02), while SDROI was slightly higher in triggered compared to nontriggered measurements in 15 out of 16 comparisons (significantly for two, P < 0.05). CONCLUSION: Registration improves the quality of DTI in native and transplanted kidneys. Diffusion parameters in renal allografts can be measured without respiratory triggering. In native kidneys, respiratory triggering appears advantageous. J. Magn. Reson. Imaging 2016;44:327-334. PMID- 26871264 TI - Radiology in the Christchurch earthquake of 22 February 2011: Challenges, interim processes and clinical priorities. AB - INTRODUCTION: The Canterbury earthquake of 22 February 2011 initiated a mass casualty event for Christchurch Hospital, which suffered damage itself, and faced logistical difficulties in continued operation. Radiology was part of the hospital-wide response. This paper reviews the radiology department response and surveys opinions of emergency doctors to provide an overview of events of the day and thoughts regarding any potential future response. METHODS: Two main approaches were undertaken: (i) informal data gathering and discussions with staff including radiographers, sonographers, radiologists, emergency doctors and others present on the day regarding their experiences; and (ii) survey of emergency doctors regarding their experiences and recommendations. A comparison with other similar events was also conducted. RESULTS: (1) Diagnostic radiology services were initially constrained by a lack of power and lift access. Usual imaging and reporting pathways were interrupted. Alternative processes were initiated to ensure an ongoing radiology service with available resources. Lessons were learned and changes implemented locally.(2) Survey data confirmed several primary outcomes: (i) Ultrasound was crucial while CT was down; (ii) all available imaging modalities remain important in a disaster response; and (iii) preliminary reports from radiologists in the emergency department (ED) were useful in the immediate post-earthquake period. CONCLUSION: Although resources were limited, a diagnostic radiology service remained operational. The Christchurch experience reinforces the need for disaster planning and rehearsal of plans. PMID- 26871265 TI - Organic Linker Defines the Excited-State Decay of Photocatalytic MIL-125(Ti)-Type Materials. AB - Recently, MIL-125(Ti) and NH2 -MIL-125(Ti), two titanium-based metal-organic frameworks, have attracted significant research attention in the field of photocatalysis for solar fuel generation. This work reveals that the differences between these structures are not only based on their light absorption range but also on the decay profile and topography of their excited states. In contrast to MIL-125(Ti), NH2 -MIL-125(Ti) shows markedly longer lifetimes of the charge separated state, which improves photoconversion by the suppression of competing decay mechanisms. We used spectroelectrochemistry and ultrafast spectroscopy to demonstrate that upon photoexcitation in NH2 -MIL-125(Ti) the electron is located in the Ti-oxo clusters and the hole resides on the aminoterephthalate unit, specifically on the amino group. The results highlight the role of the amino group in NH2 -MIL-125(Ti), the electron donation of which extends the lifetime of the photoexcited state substantially. PMID- 26871267 TI - Veterinary clinical pathology trainees benefit from toxicologic externship opportunities in the biopharmaceutical industry. PMID- 26871266 TI - Simvastatin improves the homing of BMSCs via the PI3K/AKT/miR-9 pathway. AB - Bone marrow-derived mesenchymal stem cells (BMSCs) have great therapeutic potential for many diseases. However, the homing of BMSCs to injury sites remains a difficult problem. Recent evidence indicates that simvastatin stimulates AKT phosphorylation, and p-AKT affects the expression of chemokine (CXC motif) receptor-4 (CXCR4). Therefore, simvastatin may improve the expression of CXCR4 in BMSCs, and microRNAs (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR4 in BMSCs. Stromal cell-derived factor-1alpha (SDF-1alpha)-induced migration of BMSCs was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR4). The PI3K/AKT pathway was activated by simvastatin in this process, and LY294002 reversed the overexpression of CXCR4 caused by simvastatin. MiR-9 directly targeted CXCR4 in rat BMSCs, and simvastatin decreased miR-9 expression. P-AKT affected the expression of miR-9; as the phosphorylation of AKT increased, miR-9 expression decreased. In addition, LY294002 increased miR-9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSCs via the PI3K/AKT pathway. MiR-9 also participated in this process, and the phosphorylation of AKT affected miR-9 expression, suggesting that simvastatin might have beneficial effects in stem cell therapy. PMID- 26871268 TI - A service evaluation comparing CVVH an CVVHD in minimising circuit failure. AB - BACKGROUND: A significant problem during continuous renal replacement therapy is premature circuit failure, affecting efficacy and molecular clearance. Techniques to improve circuit failure are anticoagulation, access site and modality. A modality change was introduced, moving from continuous veno-venous haemofiltration to continuous veno-venous haemodiafiltration as a result of existing issues with failing circuit times and failure rates. AIM: The aim of this service evaluation was to ascertain if the use of continuous veno-venous haemodiafiltration compared to continuous veno-venous haemofiltration had affected failed circuit survival times and rates. METHODS: A service evaluation was chosen because the focus was to ascertain what effect a practice change had had on a particular service. The service evaluation was registered with the local trust's audit department and gained university ethical approval. It was anticipated that the data generated would be used to inform, question and improve practices. Patients who received renal replacement therapy (RRT) from May 2012 to January 2013 were retrospectively identified. Patients received continuous veno venous haemofiltration for the duration of their treatment before September 2012 and continuous veno-venous haemodiafiltration after. A total of 78 patients were identified as receiving RRT; 41 of these patients had failed circuits. RESULTS: A total of 182 failed circuits were analysed. The median duration of failed circuits during continuous veno-venous haemofiltration was shorter (2.75 h, standard deviation (SD) = 13.82) when compared to continuous veno-venous haemodiafiltration (11 h, SD = 15.26, p < 0.001, 95% confidence interval (CI) 2.5 10). Circuit failure rate in continuous veno-venous haemofiltration was 56% compared to 43% in continuous veno-venous haemodiafiltration. After performing a Cox regression analysis, continuous veno-venous haemofiltration appeared to have a 1.87 times (CI 1.18-2.82, p > 0.007) more likely chance of failure. CONCLUSION: The use of continuous veno-venous haemodiafiltration has had an overall positive effect on the haemofiltration service by reducing the number of failed circuits and increasing circuit survival times, which may have improved the efficacy of the service. Continuous veno-venous haemodiafiltration may be a more appropriate modality of choice in non-septic patients requiring prolonged continuous RRT episodes. PMID- 26871269 TI - Likelihood of repeat abortion in a Swedish cohort according to the choice of post abortion contraception: a longitudinal study. AB - INTRODUCTION: Despite high access to contraceptive services, 42% of the women who seek an abortion in Sweden have a history of previous abortion(s). The reasons for this high repeat abortion rate remain obscure. The objective of this study was to study the choice of contraceptive method after abortion and related odds of repeat abortions within 3-4 years. MATERIAL AND METHODS: This is a retrospective cohort study based on a medical record review at three hospitals in Sweden. We included 987 women who had an abortion during 2009. We reviewed medical records from the date of the index abortion until the end of 2012 to establish the choice of contraception following the index abortion and the occurrence of repeat abortions. We calculated odds ratios (OR) with 95% CI. RESULTS: While 46% of the women chose oral contraceptives, 34% chose long-acting reversible contraceptives (LARC). LARC was chosen more commonly by women with a previous pregnancy, childbirth and/or abortion. During the follow-up period, 24% of the study population requested one or more repeat abortion(s). Choosing LARC at the time of the index abortion was associated with fewer repeat abortions compared with choosing oral contraceptives (13% vs. 26%, OR 0.36; 95% CI 0.24 0.52). Subdermal implant was as effective as intrauterine device in preventing repeat abortions beyond 3 years. CONCLUSIONS: Choosing LARC was associated with fewer repeat abortions over more than 3 years of follow up. PMID- 26871270 TI - Urinary C-peptide analysis in an intervention study: experience from the DEFEND-2 otelixizumab trial. AB - AIMS: To demonstrate that analysis of urinary C-peptide across multiple study sites in the context of an intervention trial (DEFEND-2) is a viable alternative to mixed meal testing and delivers results that correlate to mixed meal testing estimation of endogenous insulin production. METHODS: Second morning void urine was collected for analysis and was available from 161 subjects at baseline (55 placebo, 106 otelixizumab), and 146 subjects (47 placebo, 99 otelixizumab) at month 12. Urinary C-peptide concentration was corrected for urinary creatinine [urinary C-peptide/creatinine ratio (UCPCR)] and serum C-peptide from the mixed meal tolerance test was calculated using area under the plasma concentration-time curve (AUC) normalized over 120 min. The correlation between mixed meal stimulated C-peptide AUC (mmol/l/min) and UCPCR (nmol/mmol), as well as the correlation between insulin use (IU/kg), and HbA1c (%) with UCPCR, was determined. RESULTS: UCPCR and mixed meal testing C-peptide AUC were correlated, with a correlation coefficient of 0.4172. UCPCR was not correlated with exogenous insulin use (r = -0.089) or with HbA1c (r = -0.032). CONCLUSIONS: Urinary C peptide estimation should be considered as a measure of endogenous insulin production in future Type 1 diabetes mellitus outcome trials. A change in the timing for urine collection (to 120 min post standard meal) may provide a tighter correlation to C-peptide measured via a traditional mixed meal test. PMID- 26871271 TI - Epigenetic regulation of subgenome dominance following whole genome triplication in Brassica rapa. AB - Subgenome dominance is an important phenomenon observed in allopolyploids after whole genome duplication, in which one subgenome retains more genes as well as contributes more to the higher expressing gene copy of paralogous genes. To dissect the mechanism of subgenome dominance, we systematically investigated the relationships of gene expression, transposable element (TE) distribution and small RNA targeting, relating to the multicopy paralogous genes generated from whole genome triplication in Brassica rapa. The subgenome dominance was found to be regulated by a relatively stable factor established previously, then inherited by and shared among B. rapa varieties. In addition, we found a biased distribution of TEs between flanking regions of paralogous genes. Furthermore, the 24-nt small RNAs target TEs and are negatively correlated to the dominant expression of individual paralogous gene pairs. The biased distribution of TEs among subgenomes and the targeting of 24-nt small RNAs together produce the dominant expression phenomenon at a subgenome scale. Based on these findings, we propose a bucket hypothesis to illustrate subgenome dominance and hybrid vigor. Our findings and hypothesis are valuable for the evolutionary study of polyploids, and may shed light on studies of hybrid vigor, which is common to most species. PMID- 26871272 TI - Hysteroscopic myomectomy outcomes after 3-month treatment with either Ulipristal Acetate or GnRH analogues: a retrospective comparative study. AB - Ulipristal Acetate (UPA) modifies the endometrium, as well as fibroids, and therefore it might make hysteroscopic surgery more difficult. To confirm that pre treatment with UPA is as safe and effective an option as pre-treatment with GnRH analogues, considered the gold standard. We present the first series of 26 hysteroscopic myomectomies after 3 months treatment with UPA and we compare the results with a series of 24 cases pretreated with GnRH analogues. This was a retrospective cohort study between July 2013 and May 2015. We analyszed patients with submucous myomas >2.5 in diameter. Hysteroscopic myomectomy was performed after 3 months of treatment with either UPA (5mg daily) or the GnRH agonist (3.75mg/month). Both groups were similar in age, myoma initial size and classification. There were no significant differences between UPA and GnRHa treated groups in terms of percentage of myomas resected (93% vs 98%), duration of surgery (38 vs 37min), fluid deficit (200 vs 350ml) and complications. In the surgeon's subjective opinion, UPA treatment was associated with an easier resection. Based on our experience, previous treatment with UPA does not difficult Hhysteroscopic myomectomy. Endometrial changes have no impact on surgery. Safety and feasibility are comparable to hysteroscopic myomectomies with previous treatment with GnRH analogues. This allows us to take advantage of the reduction in size of fibroids before surgery with less side effects. PMID- 26871273 TI - The quantitative lung index and the prediction of survival in fetuses with congenital diaphragmatic hernia. AB - INTRODUCTION: The lung-to-head ratio (LHR) is routinely used to select the best candidates for prenatal surgery and to follow-up the fetuses with congenital diaphragmatic hernia (CDH). Since this index is gestation-dependent, the quantitative lung index (QLI) was proposed as an alternative parameter that stays constant throughout pregnancy. Our objective was to study the performance of QLI to predict survival in fetuses with CDH. MATERIALS AND METHODS: Observational retrospective study of fetuses with isolated CDH, referred to our center. LHR was originally used for the prenatal surgery evaluation. We calculated the QLI and compared the performance of both indexes (QLI and LHR) to predict survival. RESULTS: From January-2009 to February-2015 we followed 31 fetuses with isolated CDH. The mean QLI was 0.66 (95% CI: 0.57-0.75) for survivors and 0.41 (95% CI: 0.25-0.58) for non-survivors (p<0.01) and the mean LHR was 1.38 (95% CI: 1.17 1.60) for survivors and 0.91 (95% CI: 0.57-1.25) for non-survivors (p<0.02). All operated fetuses (n=12) had a LHR <1 and a QLI <0.5 and none of them survived when the QLI was <0.32. When separately considering the prenatal surgery status, the mean values of the QLI (but not those of the LHR) were still significantly different between survivors and non-survivors. The comparative ROC curves showed a better performance of the QLI with respect to the LHR for the prediction of survival, especially in the group of operated fetuses, although differences were not statistically significant. COMMENT: The QLI seems to be a better predictor for survival than the LHR, especially for the group of fetuses undergoing prenatal surgery. PMID- 26871274 TI - Differential contribution of orexin receptors within the ventral tegmental area to modulation of persistent inflammatory pain. AB - BACKGROUND: Orexinergic neurons in the lateral hypothalamus (LH) play an important role in pain modulation. In addition, ventral tegmental area (VTA) is known as a part of descending pain modulatory circuitry. Little is known about the interaction between the LH and neural substrates involving in modulation of formalin-induced nociception. Accordingly, we aimed to examine the pain modulatory role of VTA orexin receptors in the formalin test. METHODS: Seventy eight male Wistar rats were unilaterally implanted with two cannulae above the LH and VTA. Intra-VTA administration of SB-334867 (orexin-1 receptor antagonist) or TCS OX2 29 (orexin-2 receptor antagonist) was performed 5 min before intra-LH microinjection of carbachol (a cholinergic receptor agonist). The procedure was followed by subcutaneous injection of formalin after 5-min interval time. RESULTS: Carbachol attenuated formalin-induced biphasic pain responses and SB 334867 or TCS OX2 29 administration dose-dependently antagonized the LH-induced analgesia during both phases. Blockade of orexin-1 and -2 receptors had more profound effects on the reduction of antinociception during the late phase compared to the early phase. Also, contribution of orexin-1 receptors in mediation of LH-induced analgesia was greater than orexin-2 receptors during the late phase. CONCLUSION: Formalin test, a model of persistent inflammatory pain, mimics the conditions encountered in clinical situations. Pain modulatory role of orexinergic system in the formalin test through a neural pathway from the LH to the VTA provides the evidence that orexins can be useful therapeutic targets for chronic pain treatment. WHAT DOES THIS STUDY ADD?: There is a pathway from the lateral hypothalamus (LH) to the ventral tegmental area (VTA) which modulates biphasic formalin-induced pain. Blockade of VTA orexin receptors dose-dependently reduces LH-induced analgesia during both phases. Anti-analgesic effect of orexin receptor antagonists is more considerable during the late phase. Contribution of orexin-1 receptors to mediation of LH-induced analgesia is more than orexin-2 receptors during the late phase. PMID- 26871275 TI - Residual trapping of supercritical CO2 in oil-wet sandstone. AB - Residual trapping, a key CO2 geo-storage mechanism during the first decades of a sequestration project, immobilizes micrometre sized CO2 bubbles in the pore network of the rock. This mechanism has been proven to work in clean sandstones and carbonates; however, this mechanism has not been proven for the economically most important storage sites into which CO2 will be initially injected at industrial scale, namely oil reservoirs. The key difference is that oil reservoirs are typically oil-wet or intermediate-wet, and it is clear that associated pore-scale capillary forces are different. And this difference in capillary forces clearly reduces the capillary trapping capacity (residual trapping) as we demonstrate here. For an oil-wet rock (water contact angle theta=130 degrees ) residual CO2 saturation SCO2,r (~8%) was approximately halved when compared to a strongly water-wet rock (theta=0 degrees ; SCO2,r~15%). Consequently, residual trapping is less efficient in oil-wet reservoirs. PMID- 26871277 TI - Catalytic reduction-adsorption for removal of p-nitrophenol and its conversion p aminophenol from water by gold nanoparticles supported on oxidized mesoporous carbon. AB - A highly efficient method for removal of p-nitrophenol and its conversion p aminophenol from water was proposed using a novel catalyst-adsorbent composite of gold nanoparticles supported on functionalized mesoporous carbon (Au@CMK-3-O). The immobilized gold nanoparticles presented excellent catalytic ability to converse p-nitrophenol into p-aminophenol with the help of sodium borohydride, and the oxidized mesoporous carbon (CMK-3-O) serving as both carrier and adsorbent also exhibited high efficiency to remove p-aminophenol. The morphology and structure of the composite were characterized via SEM, TEM, FTIR and XPS analysis. Moreover, the mechanism of reaction process and the parameters of kinetics and thermodynamics were investigated. The activation energy was figured as 86.8 kJ mol(-1) for the adsorption and reduction of p-nitrophenol to p aminophenol. The thermodynamic analysis based on the rate constants evaluated by pseudo-first-order model reveals that the adsorption-reduction process is an endothermic procedure with the rise of randomness. The anti-oxidation and regeneration study indicates that Au@CMK-3-O can be reused for 6 times with more than 90% conversion efficiency and keep high activity after exposing in air for 1 month, which possesses great prospects in application of nitroaromatic pollutant removal. PMID- 26871276 TI - Magnetically separable and recyclable Fe3O4-polydopamine hybrid hollow microsphere for highly efficient peroxidase mimetic catalysts. AB - Magnetic Fe3O4-polydopamine (PDA) hybrid hollow microspheres, in which Fe3O4 nanoparticles were firmly incorporated in the cross-linked PDA shell, have been prepared through the formation of core/shell PS/Fe3O4-PDA composites based on template-induced covalent assembly method, followed by core removal in a tetrahydrofuran solution. The morphology, composition, thermal property and magnetic property of the magnetic hybrid hollow microspheres were characterized by SEM, TEM, FT-IR, XRD, TGA, and vibrating sample magnetometer, respectively. Results revealed that the magnetic hybrid hollow microspheres had about 380 nm of inner diameter and about 30 nm of shell thickness, and 13.6 emu g(-1) of magnetization saturation. More importantly, the Fe3O4-PDA hybrid hollow microspheres exhibited intrinsic peroxidase-like activity, as they could quickly catalyze the oxidation of typical substrates 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. Compared with PDA/Fe3O4 composites where Fe3O4 nanoparticles were loaded on the surface of PDA microspheres, the stability of Fe3O4-PDA hybrid hollow microspheres was greatly improved. As-prepared magnetic hollow microspheres might open up a new application field in biodetection, biocatalysis, and environmental monitoring. PMID- 26871278 TI - Development of a liquid chromatography/tandem mass spectrometry assay for the quantification of PM01183 (lurbinectedin), a novel antineoplastic agent, in mouse, rat, dog, Cynomolgus monkey and mini-pig plasma. AB - Lurbinectedin (PM01183) is a new synthetic tetrahydroisoquinoline alkaloid that binds to selected sequences in the minor groove of DNA, inducing PM01183-DNA adducts that stall replication, DNA repair and transcription and gives rise to double-strand breaks and finally, caspase-dependent apoptotic cell death. PM01183 has demonstrated clinical antitumor activity in platinum resistant/refractory ovarian cancer patients. A rapid and sensitive liquid chromatography/tandem mass spectrometry assay was developed and validated to quantify PM01183 in plasma from nonclinical species. The bioanalysis consisted of a supported liquid extraction, followed by a gradient phase chromatography and, detection by positive ion electrospray tandem mass spectrometry. The calibration range for PM01183 was established using PM01183 standards from 0.1 to 100 ng/mL in blank plasma. The multiple reaction monitoring, based on the transition m/z 767.3->273.0, was specific for PM01183, and that based on the transition m/z 771.4->277.0 was specific for the internal standard (deuterated PM01183). No endogenous material interfered with the analysis of PM01183 and the internal standard from blank plasma. The limit of detection (LOD) of the assay was calculated as 0.025 ng/mL. The correlation coefficients for the calibration curves ranged from 0.9937 to 0.9987. The mean inter-day accuracies for all calibration standards ranged from 92 to 108% (<=8% bias), and the mean inter-day precision for calibration standards was always less than 12%. The mean intra and inter-day assay accuracy for all quality control replicates remained between 91 and 109%. The mean intra and inter-day assay precision was less than 10% for all QC levels. The method was validated to demonstrate the specificity, recovery, limit of quantification, accuracy and precision of measurements. The assay has been used to support preclinical pharmacokinetic and toxicokinetic studies of PM01183 in nonclinical species. The main PK parameters in dogs (3 male and 3 female, respectively) were calculated as follows: maximum concentration (Cmax, 12.9+/-0.6 and 10.2+/-3.0 ng/mL) and the area under the plasma concentration-time curve (AUC, 24.9+/-0.7 and 22.6+/-6.1 ng h/mL). The results showed that plasma samples could be monitored for PM01183 for long enough to accurately estimate pharmacokinetics information. PMID- 26871279 TI - Forced degradation of nepafenac: Development and validation of stability indicating UHPLC method. AB - This paper presents stability study of the nonsteroidal anti-inflammatory drug (NSAID) nepafenac. In order to investigate stability of nepafenac, it was subjected to forced degradation under different stress conditions: acid and base hydrolysis, oxidation, humidity, heat and light. A novel stability indicating reverse phase ultra high performance liquid chromatographic (UHPLC) method coupled to ultraviolet detector has been developed to separate nepafenac and all related compounds (2-aminobenzophenone, Cl-thionepafenac, thionepafenac, Cl nepafenac, hydroxy-nepafenac, and cyclic-nepafenac). Efficient chromatographic separation was achieved on a Waters Acquity BEH C18 stationary phase with a gradient elution. Quantification was carried out at 235 nm at a flow rate of 0.6 mL/min(-1). The resolution between nepafenac and six potential impurities is found to be greater than 2.0. The developed method was validated with respect to specificity, LOD, LOQ, linearity, precision, accuracy and robustness. The r(2) values for nepafenac and six potential impurities were all greater than 0.999. The developed method is capable to detect impurities of nepafenac at a level of 0.005% with respect to test concentration of 1.0mg/mL. Significant degradation is observed in acid, base and oxidative degradation conditions and degradation products (DPs) were identified using mass spectrometry analysis; two of them were found to be a known process related impurities (hydroxy- and cyclic-nepafenac) whereas four degradation products were identified as new degradation impurities. The forced degradation samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.5%. PMID- 26871280 TI - Determination of residual fipronil in chicken egg and muscle by LC-MS/MS. AB - A simple, sensitive and reliable method was developed and applied to the residue analysis of fipronil in chicken egg and muscle by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Chicken egg and muscle samples were extracted with acetronitrile, then salting out by dehydration with anhydrous magnesium sulfate and sodium chloride. The extracts were purified by the C18 solid phase extraction cartridge prior to analysis by LC-MS/MS. The matrix-matched calibration curve showed a good linear within the concentration range from 0.01 to 2.00MUgkg(-1) (r(2)>=0.999). The average recoveries of fipronil at three spiked levels of 0.01, 0.1 and 1.0MUgkg(-1) ranged from 79.7% to 98.0%, and the relative standard deviations were less than 8.8%. The decision limit (CCalpha) and detection capability (CCbeta) of fipronil in chicken egg and muscle matrices were all 0.002MUgkg(-1) and 0.01MUgkg(-1), respectively. The method has also been successfully applied to monitoring fipronil in the real samples. PMID- 26871281 TI - Metabolic profile of anhydrosafflor yellow B in rats by ultra-fast liquid chromatography/quadrupole time-of-flight mass spectrometry. AB - Anhydrosafflor yellow B (AHSYB) is one of the major active water-soluble pigments from Carthamus tinctorius, which has been found to inhibit ADP-induced platelet aggregation and possess significant antioxidant activity. However, the metabolic fate of AHSYB in vivo remains unknown. In order to explore whether AHSYB is extensively metabolized, the metabolites of AHSYB in plasma, urine, bile, and feces samples after intravenous administration to the rats were investigated by ultra-fast liquid chromatography/quadrupole time-of-flight mass spectrometry (UFLC/Qq-TOF-MS/MS) combined with MetabolitepilotTM software. In total, AHSYB and 22 metabolites including both phase I and phase II metabolism processes were found and tentatively identified from the bio-samples. The metabolic pathways were involved in oxidation, reduction, hydroxylation, methylation, dimethylation, O-acetylation, hydrolyzation, sulfation, glucuronidaton, glutathionation and combination with glucose. The results showed that the renal and biliary routes play an important role in the clearance and excretion of AHSYB as well as hepatocyte metabolism. All of these results were reported for the first time and would contribute to a further understanding of the in vivo intermediated processes and metabolic mechanism of AHSYB and its analogs. PMID- 26871282 TI - Estrogen receptor-mediated miR-486-5p regulation of OLFM4 expression in ovarian cancer. AB - Estrogen signaling influences the development and progression of ovarian tumors, but the underlying mechanisms are not well understood. In a previous study we demonstrated that impairment of estrogen receptor alpha (ERalpha)-mediated olfactomedin 4 (OLFM4) expression promotes the malignant progression of endometrioid adenocarcinoma, and we identified OLFM4 as a potential target of miR 486-5p. In this study we investigated the role of OLFM4 in ovarian serous adenocarcinoma. Ovarian serous adenocarcinoma tissues had reduced OLFM4 expression. Expression of OLFM4 was positively correlated with ERalpha expression, and estrogen (E2) treatment in ovarian cancer cells induced OLFM4 expression in an ERalpha-dependent manner. In contrast to ERalpha, miR-486-5p levels were inversely correlated with OLFM4 expression in ovarian serous adenocarcinoma. Ovarian cancer cells transfected with miR-486-5p mimics showed decreased OLFM4 mRNA expression, and ovarian cancer cells treated with E2 showed reduced cellular miR-486-5p levels. OLFM4 knockdown enhanced proliferation, migration, and invasion by ovarian cancer cells. Low expression of OLFM4 was also associated with high tumor FIGO stage and poor tumor differentiation. These results suggest OLFM4 is downregulated by miR-486-5p, which contributes to ovarian cancer tumorigenesis. Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer. PMID- 26871284 TI - Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer. AB - Cytokine-induced killer (CIK) cells represent a realistic approach in cancer immunotherapy with confirmed survival benefits in the context of metastatic solid tumors. However, therapeutic effects are limited to a fraction of patients. In this study, immune-resistance elements and ideal combination therapies were explored. Initially, phenotypic analysis was performed to document CD3, CD56, NKG2D, DNAM-1, PD-L1, PD-1, CTLA-4, TIM-3, 2B4, and LAG-3 on CIK cells. Upon engagement of CIK cells with the tumor cells, expression of PD-1 on CIK cells and PD-L1 on both cells were up-regulated. Over-expression of PD-L1 levels on tumor cells via lentiviral transduction inhibited tumoricidal activity of CIK cells, and neutralizing of PD-L1/PD-1 signaling axis could enhance their tumor-killing effect. Conversely, blockade of NKG2D, a major activating receptor of CIK cells, largely caused dysfunction of CIK cells. Functional study showed an increase of NKG2D levels along with PD-L1/PD-1 blockade in the presence of other immune effector molecule secretion. Additionally, combined therapy of CIK infusion and PD-L1/PD-1 blockade caused a delay of in vivo tumor growth and exhibited a survival advantage over untreated mice. These results provide a preclinical proof of-concept for simultaneous PD-L1/PD-1 pathways blockade along with CIK infusion as a novel immunotherapy for unresectable cancers. PMID- 26871283 TI - Pinin interacts with C-terminal binding proteins for RNA alternative splicing and epithelial cell identity of human ovarian cancer cells. AB - Unlike many other human solid tumors, ovarian tumors express many epithelial markers at a high level for cell growth and local invasion. The phosphoprotein Pinin plays a key role in epithelial cell identity. We showed that clinical ovarian tumors and ovarian cancer cell lines express a high level of Pinin when compared with normal ovarian tissues and immortalized normal ovarian surface epithelial cell lines. Pinin co-localized and physically interacted with transcriptional corepressor C-terminal binding proteins, CtBP1 and CtBP2, in the nuclei of cancer cells. Knockdown of Pinin in ovarian cancer cells resulted in specific reduction of CtBP1 protein expression, cell adhesion, anchorage independent growth, and increased drug sensitivity. Whole transcriptomic comparison of next-generation RNA sequencing data between control ovarian cancer cell lines and cancer cell lines with respective knockdown of Pinin, CtBP1, and CtBP2 expression also showed reduced expression of CtBP1 mRNA in the Pinin knockdown cell lines. The Pinin knockdown cell lines shared significant overlap of differentially expressed genes and RNA splicing aberrations with CtBP1 knockdown and in a lesser degree with CtBP2 knockdown cancer cells. Hence, Pinin and CtBP are oncotargets that closely interact with each other to regulate transcription and pre-mRNA alternative splicing and promote cell adhesion and other epithelial characteristics of ovarian cancer cells. PMID- 26871285 TI - Therapeutic response and side effects of repeated radioligand therapy with 177Lu PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer. AB - Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64-82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17 2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients. PMID- 26871286 TI - Rad18 is required for functional interactions between FANCD2, BRCA2, and Rad51 to repair DNA topoisomerase 1-poisons induced lesions and promote fork recovery. AB - Camptothecin (CPT) and its analogues are chemotherapeutic agents that covalently and reversibly link DNA Topoisomerase I to its nicked DNA intermediate eliciting the formation of DNA double strand breaks (DSB) during replication. The repair of these DSB involves multiple DNA damage response and repair proteins. Here we demonstrate that CPT-induced DNA damage promotes functional interactions between BRCA2, FANCD2, Rad18, and Rad51 to repair the replication-associated DSB through homologous recombination (HR). Loss of any of these proteins leads to equal disruption of HR repair, causes chromosomal aberrations and sensitizes cells to CPT. Rad18 appears to function upstream in this repair pathway as its downregulation prevents activation of FANCD2, diminishes BRCA2 and Rad51 protein levels, formation of nuclear foci of all three proteins and recovery of stalled or collapsed replication forks in response to CPT. Taken together this work further elucidates the complex interplay of DNA repair proteins in the repair of replication-associated DSB. PMID- 26871287 TI - MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR. AB - The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability. PMID- 26871288 TI - Sodium alginate prevents progression of non-alcoholic steatohepatitis and liver carcinogenesis in obese and diabetic mice. AB - Obesity and related metabolic abnormalities play a key role in liver carcinogenesis. Non-alcoholic steatohepatitis (NASH), which is often complicated with obesity and diabetes mellitus, is associated with the development of hepatocellular carcinoma (HCC). Sodium alginate (SA), which is extracted from brown seaweeds, is marketed as a weight loss supplement because of its high viscosity and gelling properties. In the present study, we examined the effects of SA on the progression of NASH and related liver carcinogenesis in monosodium glutamate (MSG)-treated mice, which show obesity, diabetes mellitus, and NASH like histopathological changes. Male MSG-mice were intraperitoneally injected with diethylnitrosamine at 2 weeks of age, and, thereafter, they received a basal diet containing high- or low-molecular-weight SA throughout the experiment (16 weeks). At sacrifice, control MSG-treated mice fed the basal-diet showed significant obesity, hyperinsulinemia, steatosis and hepatic tumor development. SA administration suppressed body weight gain; improved insulin sensitivity, hyperinsulinemia, and hyperleptinemia; attenuated inflammation in the liver and white adipose tissue; and inhibited hepatic lipogenesis and progression of NASH. SA also reduced oxidative stress and increased anti-oxidant enzyme levels in the liver. Development of hepatic tumors, including liver cell adenoma and HCC, and hepatic pre-neoplastic lesions was significantly inhibited by SA supplementation. In conclusion, oral SA supplementation improves liver steatosis, insulin resistance, chronic inflammation, and oxidative stress, preventing the development of liver tumorigenesis in obese and diabetic mice. SA may have ability to suppress steatosis-related liver carcinogenesis in obese and diabetic subjects. PMID- 26871289 TI - Lipid tethering of breast tumor cells enables real-time imaging of free-floating cell dynamics and drug response. AB - Free-floating tumor cells located in the blood of cancer patients, known as circulating tumor cells (CTCs), have become key targets for studying metastasis. However, effective strategies to study the free-floating behavior of tumor cells in vitro have been a major barrier limiting the understanding of the functional properties of CTCs. Upon extracellular-matrix (ECM) detachment, breast tumor cells form tubulin-based protrusions known as microtentacles (McTNs) that play a role in the aggregation and re-attachment of tumor cells to increase their metastatic efficiency. In this study, we have designed a strategy to spatially immobilize ECM-detached tumor cells while maintaining their free-floating character. We use polyelectrolyte multilayers deposited on microfluidic substrates to prevent tumor cell adhesion and the addition of lipid moieties to tether tumor cells to these surfaces through interactions with the cell membranes. This coating remains optically clear, allowing capture of high resolution images and videos of McTNs on viable free-floating cells. In addition, we show that tethering allows for the real-time analysis of McTN dynamics on individual tumor cells and in response to tubulin-targeting drugs. The ability to image detached tumor cells can vastly enhance our understanding of CTCs under conditions that better recapitulate the microenvironments they encounter during metastasis. PMID- 26871290 TI - Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer. AB - Diallyl disulfide (DADS) has been shown to have multi-targeted antitumor activities. We have previously discovered that it has a repressive effect on LIM kinase-1 (LIMK1) expression in gastric cancer MGC803 cells. This suggests that DADS may inhibit epithelial-mesenchymal transition (EMT) by downregulating LIMK1, resulting in the inhibition of invasion and growth in gastric cancer. In this study, we reveal that LIMK1 expression is correlated with tumor differentiation, invasion depth, clinical stage, lymph node metastasis, and poor prognosis. DADS downregulated the Rac1-Pak1/Rock1-LIMK1 pathway in MGC803 cells, as shown by decreased p-LIMK1 and p-cofilin1 levels, and suppressed cell migration and invasion. Knockdown and overexpression experiments performed in vitro demonstrated that downregulating LIMK1 with DADS resulted in restrained EMT that was coupled with decreased matrix metalloproteinase-9 (MMP-9) and increased tissue inhibitor of metalloproteinase-3 (TIMP-3) expression. In in vitro and in vivo experiments, the DADS-induced suppression of cell proliferation was enhanced and antagonized by the knockdown and overexpression of LIMK1, respectively. Similar results were observed for DADS-induced changes in the expression of vimentin, CD34, Ki-67, and E-cadherin in xenografted tumors. These results indicate that downregulation of LIMK1 by DADS could explain the inhibition of EMT, invasion and proliferation in gastric cancer cells. PMID- 26871292 TI - Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells. AB - We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the "TNF network", has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate.The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets. To achieve our aim, we used a systems biology approach, combining data from phospho proteomic mass spectrometry and gene expression array analysis. Among the potential therapeutic kinase targets identified was the protein kinase Casein kinase II (CK2).Knockdown of CK2 expression in malignant cells by siRNA or treatment with the specific CK2 inhibitor CX-4945 significantly decreased Notch signaling and reduced constitutive cytokine release in ovarian cancer cell lines that expressed the TNF network as well as malignant cells isolated from high grade serous ovarian cancer ascites. The expression of the same cytokines was also inhibited after treatment with CX-4945 in a 3D organotypic model. CK2 inhibition was associated with concomitant inhibition of proliferative activity, reduced angiogenesis and experimental peritoneal ovarian tumor growth.In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer. PMID- 26871291 TI - Establishment of an integrated model incorporating standardised uptake value and N-classification for predicting metastasis in nasopharyngeal carcinoma. AB - BACKGROUND: Previous studies reported a correlation between the maximum standardised uptake value (SUVmax) obtained by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and distant metastasis in nasopharyngeal carcinoma (NPC). However, an integrated model incorporating SUVmax and anatomic staging for stratifying metastasis risk has not been reported. RESULTS: The median SUVmax for primary tumour (SUV-T) and cervical lymph nodes (SUV-N) was 13.6 (range, 2.2 to 39.3) and 8.4 (range, 2.6 to 40.9), respectively. SUV-T (HR, 3.396; 95% CI, 1.451-7.947; P = 0.005), SUV-N (HR, 2.688; 95%CI, 1.250-5.781; P = 0.011) and N-classification (HR, 2.570; 95%CI, 1.422-4.579; P = 0.001) were identified as independent predictors for DMFS from multivariate analysis. Three valid risk groups were derived by RPA: low risk (N0-1 + SUV-T <10.45), medium risk (N0-1 + SUV-T >10.45) and high risk (N2-3). The three risk groups contained 100 (22.3%), 226 (50.3%), and 123 (27.4%) patients, respectively, with corresponding 3-year DMFS rates of 99.0%, 91.5%, and 77.5% (P <0.001). Moreover, multivariate analysis confirmed the RPA-based prognostic grouping as the only significant prognostic indicator for DMFS (HR, 3.090; 95%CI, 1.975-4.835; P <0.001). METHODS: Data from 449 patients with with histologically-confirmed, stage I-IVB NPC treated with radiotherapy or chemoradiotherapy were retrospectively analysed. A prognostic model for distant metastasis-free survival (DMFS) was derived by recursive partitioning analysis (RPA) combining independent predictors identified by multivariate analysis. CONCLUSION: SUV-T, SUV-N and N classification were identified as independent predictors for DMFS. An integrated RPA-based prognostic model for DMFS incorporating SUV-N and N-classification was proposed. PMID- 26871293 TI - Arsenic trioxide inhibits glioma cell growth through induction of telomerase displacement and telomere dysfunction. AB - Glioblastomas are resistant to many kinds of treatment, including chemotherapy, radiation and other adjuvant therapies. As2O3 reportedly induces ROS generation in cells, suggesting it may be able to induce telomerase suppression and telomere dysfunction in glioblastoma cells. We show here that As2O3 induces ROS generation as well as telomerase phosphorylation in U87, U251, SHG4 and C6 glioma cells. It also induces translocation of telomerase from the nucleus to the cytoplasm, thereby decreasing total telomerase activity. These effects of As2O3 trigger an extensive DNA damage response at the telomere, which includes up-regulation of ATM, ATR, 53BP1, gamma-H2AX and Mer11, in parallel with telomere fusion and 3' overhang degradation. This ultimately results in induction of p53- and p21 mediated cell apoptosis, G2/M cell cycle arrest and cellular senescence. These results provide new insight into the antitumor effects of As2O3 and can perhaps contribute to solving the problem of glioblastoma treatment resistance. PMID- 26871294 TI - The relationship between EZH2 expression and microRNA-31 in colorectal cancer and the role in evolution of the serrated pathway. AB - Polycomb group protein enhancer of zeste homolog 2 (EZH2) is a methyltransferase that correlates with the regulation of invasion and metastasis and is overexpressed in human cancers such as colorectal cancer. MicroRNA-31 (miR-31) plays an oncogenic role and is associated with BRAF mutation and poor prognosis in colorectal cancer. EZH2 is functionally considered to suppress miR-31 expression in human cancers; however, no study has reported its relationship with colon cancer. We therefore evaluated EZH2 expression using immunohistochemistry and assessed miR-31 and epigenetic alterations using 301 colorectal carcinomas and 207 premalignant lesions. Functional analysis was performed to identify the association between EZH2 and miR-31 using cancer cell lines. In the current study, negative, weak, moderate, and strong EZH2 expressions were observed in 15%, 19%, 25%, and 41% of colorectal cancers, respectively. EZH2 was inversely associated with miR-31 (P < 0.0001), independent of clinicopathological and molecular features. In a multivariate stage-stratified analysis, high EZH2 expression was related to favorable prognosis (P = 0.0022). Regarding premalignant lesions, negative EZH2 expression was frequently detected in sessile serrated adenomas/polyps (SSA/Ps) (76%; P < 0.0001) compared with hyperplastic polyps, traditional serrated adenomas, and non-serrated adenomas (25-36%). Functional analysis demonstrated that the knockdown of EZH2 increased miR-31 expression. In conclusion, an inverse association was identified between EZH2 and miR-31 in colorectal cancers. Our data also showed that upregulation of EZH2 expression may be rare in SSA/Ps. These results suggest that EZH2 suppresses miR 31 in colorectal cancer and may correlate with differentiation and evolution of serrated pathway. PMID- 26871296 TI - Immunogenicity and safety of xenogeneic vascular endothelial growth factor receptor-2 DNA vaccination in mice and dogs. AB - Vascular endothelial growth factor receptor-2 (VEGFR-2) is an attractive target in oncology due to its crucial role in angiogenesis. In this study a DNA vaccine coding for human VEGFR-2 was evaluated in healthy mice and dogs, administered by intradermal injection and electroporation. In mice, three doses and vaccination schedules were evaluated. Cellular immune responses were measured by intracellular IFN-gamma staining and a cytotoxicity assay and antibodies by ELISA. Safety was assessed by measuring regulatory T cells and myeloid derived suppressor cells and a wound healing assay. The vaccine was subsequently evaluated in dogs, which were vaccinated three times with 100ug. Cellular immune responses were measured by intracellular IFN-gamma staining and antibodies by a flow cytometric assay. In mice, maximal cellular responses were observed after two vaccinations with 5ug. Humoral responses continued to increase with higher dose and number of vaccinations. No abnormalities in the measured safety parameters were observed. The vaccine was also capable of eliciting a cellular and humoral immune response in dogs. No adverse effects were observed, but tolerability of the electroporation was poor. This study will facilitate the evaluation of the vaccine in tumor bearing animals, ranging from rodent models to dogs with spontaneous tumors. PMID- 26871297 TI - Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study. AB - BACKGROUND: Extended-release guanfacine hydrochloride (GXR), a selective alpha2A adrenergic agonist, is a nonstimulant medication for attention deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD. METHODS: Children/adolescents (6 17 years) with ADHD received open-label GXR (1-7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (>=50% increase in ADHD Rating Scale version IV total score and >=2-point increase in Clinical Global Impression-Severity compared with RWP baseline, at two consecutive visits). The key secondary endpoint was time to treatment failure (TTF). TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01081145; EudraCT 2009-018161-12. RESULTS: A total of 528 participants enrolled; 316 (59.8%) entered the RWP. Treatment failure occurred in 49.3% of the GXR and 64.9% of the placebo group (p = 0.006). TTF was significantly longer in GXR versus placebo (p = 0.003). GXR was well tolerated. CONCLUSIONS: Guanfacine hydrochloride demonstrated long-term maintenance of efficacy compared with placebo in children/adolescents with ADHD. Implications of the placebo substitution design and findings with different ADHD medications are discussed. PMID- 26871298 TI - Fluorescence-Based Transport Assays Revisited in a Human Renal Proximal Tubule Cell Line. AB - Apical transport is key in renal function, and the activity of efflux transporters and receptor-mediated endocytosis is pivotal in this process. The conditionally immortalized proximal tubule epithelial cell line (ciPTEC) endogenously expresses these systems. Here, we used ciPTEC to investigate the activity of three major efflux transporters, viz., breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp), as well as protein uptake through receptor-mediated endocytosis, using a fluorescence-based setup for transport assays. To this end, cells were exposed to Hoechst33342, chloromethylfluorescein-diacetate (CMFDA), and calcein-AM in the presence or absence of model inhibitors for BCRP (KO143), P-gp (PSC833), or MRPs (MK571). Overexpression cell lines MDCKII-BCRP and MDCKII-P-gp were used as positive controls, and membrane vesicles overexpressing one transporter were used to determine substrate and inhibitor specificities. Receptor-mediated endocytosis was investigated by determining the intracellular accumulation of fluorescently labeled receptor-associated protein (RAP-GST). In ciPTEC, BCRP and P-gp showed similar expressions and activities, whereas MRP4 was more abundantly expressed. Hoechst33342, GS-MF, and calcein are retained in the presence of KO143, MK571, and PSC833, showing clearly redundancy between the transporters. Noteworthy is the fact that both KO143 and MK571 can block BCRP, P-gp, and MRPs, whereas PSC833 appears to be a potent inhibitor for BCRP and P-gp but not the MRPs. Furthermore, ciPTEC accumulates RAP-GST in intracellular vesicles in a dose- and time dependent manner, which was reduced in megalin-deficient cells. In conclusion, fluorescent-probe-based assays are fast and reproducible in determining apical transport mechanisms, in vitro. We demonstrate that typical substrates and inhibitors are not specific for the designated transporters, reflecting the complex interactions that can take place in vivo. The set of tools we describe are also compatible with innovative kidney culture models and allows studying transport mechanisms that are central to drug absorption, disposition, and detoxification. PMID- 26871295 TI - miR-451a is underexpressed and targets AKT/mTOR pathway in papillary thyroid carcinoma. AB - Papillary Thyroid Carcinoma (PTC) is the most frequent thyroid cancer. Although several PTC-specific miRNA profiles have been reported, only few upregulated miRNAs are broadly recognized, while less consistent data are available about downregulated miRNAs. In this study we investigated miRNA deregulation in PTC by miRNA microarray, analysis of a public dataset from The Cancer Genome Atlas (TCGA), literature review and meta-analysis based on a univocal miRNA identifier derived from miRBase v21. A list of 18 miRNAs differentially expressed between PTC and normal thyroid was identified and validated in the TCGA dataset. Furthermore, we compared our signature with miRNA profiles derived from 15 studies selected from literature. Then, to select possibly functionally relevant miRNA, we integrated our miRNA signature with those from two in vitro cell models based on the PTC-driving oncogene RET/PTC1. Through this strategy, we identified commonly deregulated miRNAs, including miR-451a, which emerged also by our meta analysis as the most frequently reported downregulated miRNA. We showed that lower expression of miR-451a correlates with aggressive clinical-pathological features of PTC as tall cell variant, advanced stage and extrathyroid extension. In addition, we demonstrated that ectopic expression of miR-451a impairs proliferation and migration of two PTC-derived cell lines, reduces the protein levels of its recognized targets MIF, c-MYC and AKT1 and attenuates AKT/mTOR pathway activation.Overall, our study provide both an updated overview of miRNA deregulation in PTC and the first functional evidence that miR-451a exerts tumor suppressor functions in this neoplasia. PMID- 26871299 TI - Using thermal balance model to determine optimal reactor volume and insulation material needed in a laboratory-scale composting reactor. AB - A comprehensive model of thermal balance and degradation kinetics was developed to determine the optimal reactor volume and insulation material. Biological heat production and five channels of heat loss were considered in the thermal balance model for a representative reactor. Degradation kinetics was developed to make the model applicable to different types of substrates. Simulation of the model showed that the internal energy accumulation of compost was the significant heat loss channel, following by heat loss through reactor wall, and latent heat of water evaporation. Lower proportion of heat loss occurred through the reactor wall when the reactor volume was larger. Insulating materials with low densities and low conductive coefficients were more desirable for building small reactor systems. Model developed could be used to determine the optimal reactor volume and insulation material needed before the fabrication of a lab-scale composting system. PMID- 26871300 TI - A Novel Mechanistic Study on Ultrasound-Assisted, One-Pot Synthesis of Functionalized Benzimidazo[2,1-b]quinazolin-1(1H)-ones. AB - Ultrasound-assisted synthesis of benzimidazo[2,1-b]quinazolin-1(1H)-ones was achieved via piperidine-catalyzed three-component reaction of 2 aminobenzimidazoles, an aromatic aldehyde, and 1,3-dione in aqueous isopropanol. This mechanism was first suspected following our identification of unusual reaction intermediates in a one-pot reaction. An unprecedented coupling reaction, it involved a nucleophilic attack by 2-aminobenzimidazole on in situ generated Michael adduct, followed by electrocyclic ring formation reaction. In contrast to the commonly accepted mechanism, that the direct reaction of 2-amino benzimidazole with a Knoevenagel adduct cannot deliver target compounds. PMID- 26871301 TI - Life-Cycle Assessment of Advanced Nutrient Removal Technologies for Wastewater Treatment. AB - Advanced nutrient removal processes, while improving the water quality of the receiving water body, can also produce indirect environmental and health impacts associated with increases in usage of energy, chemicals, and other material resources. The present study evaluated three levels of treatment for nutrient removal (N and P) using 27 representative treatment process configurations. Impacts were assessed across multiple environmental and health impacts using life cycle assessment (LCA) following the Tool for the Reduction and Assessment of Chemical and Other Environmental Impacts (TRACI) impact-assessment method. Results show that advanced technologies that achieve high-level nutrient removal significantly decreased local eutrophication potential, while chemicals and electricity use for these advanced treatments, particularly multistage enhanced tertiary processes and reverse osmosis, simultaneously increased eutrophication indirectly and contributed to other potential environmental and health impacts including human and ecotoxicity, global warming potential, ozone depletion, and acidification. Average eutrophication potential can be reduced by about 70% when Level 2 (TN = 3 mg/L; TP = 0.1 mg/L) treatments are employed instead of Level 1 (TN = 8 mg/L; TP = 1 mg/L), but the implementation of more advanced tertiary processes for Level 3 (TN = 1 mg/L; TP = 0.01 mg/L) treatment may only lead to an additional 15% net reduction in life-cycle eutrophication potential. PMID- 26871303 TI - Dyadic Transition to Parenthood: A Longitudinal Assessment of Personal Growth among Parents of Pre- and Full-term Infants. AB - This study examined the contribution of birth circumstances (premature and full term birth) and individual and spousal factors (attachment orientations, parental self-efficacy and perceived infant temperament), measured 1 month post-partum, to the personal growth of first-time parents (n = 121) 1 and 5 months post-partum. The study overcame the limitations of prior research by accurately measuring actor effects while controlling for and assessing partner effects, by applying the actor-partner interdependence model. The findings confirm that becoming a parent, under normative and stressful circumstances, can lead to personal growth and parents of premature babies experience higher levels of growth than parents of full terms. Moreover, 1 month post-partum, actor effects were found for higher attachment anxiety and higher parental self-efficacy. Furthermore, personal growth at 1 month post-partum was found to be the strongest predictor of personal growth 5 months after childbirth. Five months post-partum, a positive partner effect was found for parental self-efficacy. Mothers reported higher growth than fathers only 5 months after the birth. It seems time plays an important role as to which variables contribute to personal growth. In the early stages of parenthood, personal growth is mostly an individual experience. Theoretical and clinical implications are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26871304 TI - Recent progress in imidoyl radical-involved reactions. AB - Much attention has been paid to imidoyl radical-involved reactions in recent years. As a divergent reactive intermediate, imidoyl radicals are used for the synthesis of functionalized heterocycles, nitriles, imines, amines, etc. This review is intended to highlight some recent progress in the past decade. PMID- 26871302 TI - A General Approach for Generating Fluorescent Probes to Visualize Piconewton Forces at the Cell Surface. AB - Mechanical forces between cells and their extracellular matrix (ECM) are mediated by dozens of different receptors. These biophysical interactions play fundamental roles in processes ranging from cellular development to tumor progression. However, mapping the spatial and temporal dynamics of tension among various receptor-ligand pairs remains a significant challenge. To address this issue, we have developed a synthetic strategy to generate modular tension probes combining the native chemical ligation (NCL) reaction with solid phase peptide synthesis (SPPS). In principle, this approach accommodates virtually any peptide or expressed protein amenable to NCL. We generated a small library of tension probes displaying different ligands, flexible linkers, and fluorescent reporters, enabling the mapping of integrin and cadherin tension, and demonstrating the first example of long-term (~3 days) molecular tension imaging. This approach provides a toolset to better understand mechanotransduction events fundamental to cell biology. PMID- 26871305 TI - Digitized morphometric analysis of dental pulp of permanent mandibular second molar for age estimation of Davangere population. AB - OBJECTIVE: The aim of the present study is to estimate the age of Davangere population by evaluating the pulp to tooth area ratio (PTR) by using digitized intraoral periapical radiographs of permanent mandibular second molar. METHODS: 400 intraoral periapical radiograph (IOPA) of permanent mandibular 2nd molar of both the sexes aged 14-60 years were used. Digital camera was used to image the radiographs. Images were computed and PTR was calculated by AUTOCAD software. Intra and Inter observer variability was also assessed. Regression analysis was used to estimate the age of an individual by taking PTR as dependent variable. RESULTS: The mean PTR of males and females was 0.10 +/- 0.02 and 0.09 +/- 0.02 respectively. Negative correlation was observed, when age was compared with PTR {r = -0.441, -0.406 & -0.419 among males, females and total subjects (p < 0.001)}. Regression analysis showed a Standard Error of Estimate (SEE) of 12 years. The Kappa coefficient value for the intra and inter examiner variability was 0.85 & 0.83 respectively. CONCLUSION: Our results showed that permanent mandibular 2(nd) molar can be taken as an index tooth for estimating the age of the adults using digitized periapical radiograph and AUTOCAD software. Also high differences were observed between estimated and chronological age of 12 years which is not in the acceptable range. But it provides a new window for research in the forensic sciences in estimating the adult age. PMID- 26871306 TI - Intra- and extra-familial child homicide in Sweden 1992-2012: A population-based study. AB - Previous studies have shown decreasing child homicide rates in many countries - in Sweden mainly due to a drop in filicide-suicides. This study examines the rate of child homicides during 21 years, with the hypothesis that a decline might be attributable to a decrease in the number of depressive filicide offenders (as defined by a proxy measure). In addition, numerous characteristics of child homicide are presented. All homicide incidents involving 0-14-year-old victims in Sweden during 1992-2012 (n = 90) were identified in an autopsy database. Data from multiple registries, forensic psychiatric evaluations, police reports, verdicts and other sources were collected. Utilizing Poisson regression, we found a 4% annual decrease in child homicides, in accordance with prior studies, but no marked decrease regarding the depressive-offender proxy. Diagnoses from forensic psychiatric evaluations (n = 50) included substance misuse (8%), affective disorders (10%), autism-spectrum disorders (18%), psychotic disorders (28%) and personality disorders (30%). Prior violent offences were more common among offenders in filicides than filicide-suicides (17.8% vs. 6.9%); and about 20% of offenders in each group had previously received psychiatric inpatient care. Aggressive methods of filicide predominated among fathers. Highly lethal methods of filicide (firearms, fire) were more commonly followed by same-method suicide than less lethal methods. Interestingly, a third of the extra-familial offenders had an autism-spectrum disorder. Based on several findings, e.g., the low rate of substance misuse, the study concludes that non-traditional risk factors for violence must be highlighted by healthcare providers. Also, the occurrence of autism-spectrum disorders in the present study is a novel finding that warrants further investigation. PMID- 26871307 TI - Enantioselective Total Synthesis of Lycoposerramine-Z Using Chiral Phosphoric Acid Catalyzed Intramolecular Michael Addition. AB - A new enantioselective total synthesis of phlegmarine-type Lycopodium alkaloid lycoposerramine-Z (1) has been accomplished, using one-pot chemoselective sequential additions of two different Grignard reagents to the bis-Weinreb-amide intermediate and an efficient construction of the fully fuctionalized cyclohexanone intermediate with a chiral phosphoric acid catalyzed enantioselective intramolecular Michael addition. PMID- 26871308 TI - Tuning the surface structure of supported PtNi(x) bimetallic electrocatalysts for the methanol electro-oxidation reaction. AB - The structures of PtNix nanoalloy particles were modified through thermal annealing in different atmospheres. The evolution of surface structures was uncovered by advanced transmission electron microscopy, and the structure function correlation in methanol electro-oxidation was probed. It provided new insights into the design and synthesis of highly efficient electrocatalysts. PMID- 26871309 TI - Total facial selectivity of a D-erythrosyl aromatic imine in [4pi + 2pi] cycloadditions; synthesis of 2-alkylpolyol 1,2,3,4-tetrahydroquinolines. AB - Different electron-rich dienophiles were combined with the imine obtained from 2,4-O-benzylidene-d-erythrose and p-anisidine furnishing enantiomerically pure tetrahydroquinolines, by inverse electron-demand [4pi + 2pi] cycloaddition. The imine was also reacted with 2-substituted electron-rich 1,3-butadienes giving the diastereomeric pure product, resulting from the normal electron demand cycloaddition. The facial selectivity of both processes is proposed on the basis of a 1,4-relationship between the hydroxyl group and the nitrogen atom in the chiral N-(p-methoxyphenyl)imine derivative. PMID- 26871311 TI - Synthesis and spectral measurements of sulphonated graphene: some anomalous observations. AB - The present report demonstrates how a sulphonation process, a key route for synthesizing water soluble graphene, can influence the optical behavior of precursor graphene oxide, intermediate reaction products and sulphonated graphene. We observed that there is constant emission maximum at 500 nm for graphene oxide in the excitation range of 320-450 nm. During sulphonation, sulphonated reduced graphene oxide (rGO-SO3H) is initially formed which has an emission at 358 nm. However, the reduction of oxygen containing groups in rGO SO3H with hydrazine hydrate leading to the formation of SG caused a shift in the emission to 430 nm, which has been attributed to the extended delocalization of pi-electrons involving the phenyl sulphonate group. In the present investigation, we have identified many existing anomalies in the important spectral features of these materials, such as violation of Kasha's rule on fluorescence and pH dependence emission. Furthermore, it has also been shown that proper care is necessary to be taken in monitoring the fluorescence of sulphonated graphene in view of possible interference from the components produced during sulphonation. PMID- 26871310 TI - A rock in a hard place: Cement pulmonary emboli after percutaneous vertebroplasty. PMID- 26871312 TI - Utilizing a Key Aptamer Structure-Switching Mechanism for the Ultrahigh Frequency Detection of Cocaine. AB - Aptasensing of small molecules remains a challenge as detection often requires the use of labels or signal amplification methodologies, resulting in both difficult-to-prepare sensor platforms and multistep, complex assays. Furthermore, many aptasensors rely on the binding mechanism or structural changes associated with target capture by the aptameric probe, resulting in a detection scheme customized to each aptamer. It is in this context that we report herein a sensitive cocaine aptasensor that offers both real-time and label-free measurement capabilities. Detection relies on the electromagnetic piezoelectric acoustic sensor (EMPAS) platform. The sensing interface consists of a S-(11 trichlorosilyl-undecanyl)benzenethiosulfonate (BTS) adlayer-coated quartz disc onto which a structure-switching cocaine aptamer (MN6) is immobilized, completing the preparation of the MN6 cocaine aptasensor (M6CA). The EMPAS system has recently been employed as the foundation of a cocaine aptasensor based on a structurally rigid cocaine aptamer variant (MN4), an aptasensor referred to by analogy as M4CA. M6CA represents a significant increase in terms of analytical performance, compared to not only M4CA but also other cocaine aptamer-based sensors that do not rely on signal amplification, producing an apparent K(d) of 27 +/- 6 MUM and a 0.3 MUM detection limit. Remarkably, the latter is in the range of that achieved by cocaine aptasensors relying on signal amplification. Furthermore, M6CA proved to be capable not only of regaining its cocaine-binding ability via simple buffer flow over the sensing interface (i.e., without the necessity to implement an additional regeneration step, such as in the case of M4CA), but also of detecting cocaine in a multicomponent matrix possessing potentially assay-interfering species. Finally, through observation of the distinct shape of its response profiles to cocaine injection, demonstration was made that the EMPAS system in practice offers the possibility to distinguish between the binding mechanisms of structure-switching (MN6) vs rigid (MN4) aptameric probes, an ability that could allow the EMPAS to provide a more universal aptasensing platform than what is ordinarily observed in the literature. PMID- 26871313 TI - Local Scale Transformations on the Lattice with Tensor Network Renormalization. AB - Consider the partition function of a classical system in two spatial dimensions, or the Euclidean path integral of a quantum system in two space-time dimensions, both on a lattice. We show that the tensor network renormalization algorithm [G. Evenbly and G. Vidal Phys. Rev. Lett. 115, 180405 (2015)] can be used to implement local scale transformations on these objects, namely, a lattice version of conformal maps. Specifically, we explain how to implement the lattice equivalent of the logarithmic conformal map that transforms the Euclidean plane into a cylinder. As an application, and with the 2D critical Ising model as a concrete example, we use this map to build a lattice version of the scaling operators of the underlying conformal field theory, from which one can extract their scaling dimensions and operator product expansion coefficients. PMID- 26871314 TI - Permutation Symmetry Determines the Discrete Wigner Function. AB - The Wigner function provides a useful quasiprobability representation of quantum mechanics, with applications in various branches of physics. Many nice properties of the Wigner function are intimately connected with the high symmetry of the underlying operator basis composed of phase point operators: any pair of phase point operators can be transformed to any other pair by a unitary symmetry transformation. We prove that, in the discrete scenario, this permutation symmetry is equivalent to the symmetry group being a unitary 2 design. Such a highly symmetric representation can only appear in odd prime power dimensions besides dimensions 2 and 8. It suffices to single out a unique discrete Wigner function among all possible quasiprobability representations. In the course of our study, we show that this discrete Wigner function is uniquely determined by Clifford covariance, while no Wigner function is Clifford covariant in any even prime power dimension. PMID- 26871315 TI - Strong Measurements Give a Better Direct Measurement of the Quantum Wave Function. AB - Weak measurements have thus far been considered instrumental in the so-called direct measurement of the quantum wave function [4J. S. Lundeen, Nature (London) 474, 188 (2011).]. Here we show that a direct measurement of the wave function can be obtained by using measurements of arbitrary strength. In particular, in the case of strong measurements, i.e., those in which the coupling between the system and the measuring apparatus is maximum, we compared the precision and the accuracy of the two methods, by showing that strong measurements outperform weak measurements in both for arbitrary quantum states in most cases. We also give the exact expression of the difference between the original and reconstructed wave function obtained by the weak measurement approach; this will allow one to define the range of applicability of such a method. PMID- 26871316 TI - Soluble Model Fluids with Complete Scaling and Yang-Yang Features. AB - Yang-Yang (YY) and singular diameter critical anomalies arise in exactly soluble compressible cell gas (CCG) models that obey complete scaling with pressure mixing. Thus, on the critical isochore rho=rho(c), C(MU)?-Td(2)MU/dT(2) diverges as |t|^(-alpha) when t?T-T(c)->0^(-) while rho(d)-rho(c)~|t|^(2beta) where rho(d)(T)=1/2[rho(liq)+rho(gas)]. When the discrete local CCG cell volumes fluctuate freely, the YY ratio R(MU)=C(MU)/C(V) may take any value infinity0. More general decorated CCGs, including "hydrogen bonding" water models, illuminate energy-volume coupling as relevant to R(MU). PMID- 26871317 TI - New Features of Gravitational Collapse in Anti-de Sitter Spacetimes. AB - Gravitational collapse of a massless scalar field in spherically symmetric anti de Sitter (AdS) spacetimes presents a new phenomenology with a series of critical points whose dynamics is discretely self-similar as in the asymptotically flat case. Each critical point is the limit of a branch of scalar field configurations that have bounced off the AdS boundary a fixed number of times before forming an apparent horizon. We present results from a numerical study that focus on the interfaces between branches. We find that there is a mass gap between branches and that subcritical configurations near the critical point form black holes with an apparent horizon mass that follows a power law of the form M(AH)-M(g)?(p(c) p)^(xi), where M(g) is the mass gap and the exponent xi?0.7 appears to be universal. PMID- 26871318 TI - Audio-Band Frequency-Dependent Squeezing for Gravitational-Wave Detectors. AB - Quantum vacuum fluctuations impose strict limits on precision displacement measurements, those of interferometric gravitational-wave detectors among them. Introducing squeezed states into an interferometer's readout port can improve the sensitivity of the instrument, leading to richer astrophysical observations. However, optomechanical interactions dictate that the vacuum's squeezed quadrature must rotate by 90 degrees around 50 Hz. Here we use a 2-m-long, high finesse optical resonator to produce frequency-dependent rotation around 1.2 kHz. This demonstration of audio-band frequency-dependent squeezing uses technology and methods that are scalable to the required rotation frequency and validates previously developed theoretical models, heralding application of the technique in future gravitational-wave detectors. PMID- 26871320 TI - Dark Matter Halos as Particle Colliders: Unified Solution to Small-Scale Structure Puzzles from Dwarfs to Clusters. AB - Astrophysical observations spanning dwarf galaxies to galaxy clusters indicate that dark matter (DM) halos are less dense in their central regions compared to expectations from collisionless DM N-body simulations. Using detailed fits to DM halos of galaxies and clusters, we show that self-interacting DM (SIDM) may provide a consistent solution to the DM deficit problem across all scales, even though individual systems exhibit a wide diversity in halo properties. Since the characteristic velocity of DM particles varies across these systems, we are able to measure the self-interaction cross section as a function of kinetic energy and thereby deduce the SIDM particle physics model parameters. Our results prefer a mildly velocity-dependent cross section, from sigma/m~2 cm^{2}/g on galaxy scales to sigma/m~0.1 cm^{2}/g on cluster scales, consistent with the upper limits from merging clusters. Our results dramatically improve the constraints on SIDM models and may allow the masses of both DM and dark mediator particles to be measured even if the dark sector is completely hidden from the standard model, which we illustrate for the dark photon model. PMID- 26871319 TI - Evidence of Halo Assembly Bias in Massive Clusters. AB - We present significant evidence of halo assembly bias for SDSS redMaPPer galaxy clusters in the redshift range [0.1, 0.33]. By dividing the 8,648 clusters into two subsamples based on the average member galaxy separation from the cluster center, we first show that the two subsamples have very similar halo mass of M_{200m}?1.9*10^{14} h^{-1}M_{?} based on the weak lensing signals at small radii R?10 h^{-1}Mpc. However, their halo bias inferred from both the large scale weak lensing and the projected autocorrelation functions differs by a factor of ~1.5, which is a signature of assembly bias. The same bias hypothesis for the two subsamples is excluded at 2.5sigma in the weak lensing and 4.4sigma in the autocorrelation data, respectively. This result could bring a significant impact on both galaxy evolution and precision cosmology. PMID- 26871321 TI - On-Shell Recursion Relations for Effective Field Theories. AB - We derive the first ever on-shell recursion relations applicable to effective field theories. Based solely on factorization and the soft behavior of amplitudes, these recursion relations employ a new rescaling momentum shift to construct all tree-level scattering amplitudes in the nonlinear sigma model, Dirac-Born-Infeld theory, and the Galileon. Our results prove that all theories with enhanced soft behavior are on-shell constructible. PMID- 26871326 TI - Doppler Cooling Trapped Ions with a UV Frequency Comb. AB - We demonstrate Doppler cooling of trapped magnesium ions using a frequency comb at 280 nm obtained from a frequency tripled Ti:sapphire laser. A comb line cools on the 3s_{1/2}-3p_{3/2} transition, while the nearest blue-detuned comb line contributes negligible heating. We observe the cooling-heating transition and long-term cooling of ion chains with several sympathetically cooled ions. Spatial thermometry shows that the ion is cooled to near the Doppler limit. Doppler cooling with frequency combs has the potential to open many additional atomic species to laser cooling by reaching further into the vacuum and extreme ultraviolet via high-harmonic generation and by providing a broad bandwidth from which multiple excitation sidebands can be obtained. PMID- 26871324 TI - Observation of Anomalous Internal Pair Creation in ^{8}Be: A Possible Indication of a Light, Neutral Boson. AB - Electron-positron angular correlations were measured for the isovector magnetic dipole 17.6 MeV (J^{pi}=1^{+}, T=1) state->ground state (J^{pi}=0^{+}, T=0) and the isoscalar magnetic dipole 18.15 MeV (J^{pi}=1^{+}, T=0) state->ground state transitions in ^{8}Be. Significant enhancement relative to the internal pair creation was observed at large angles in the angular correlation for the isoscalar transition with a confidence level of >5sigma. This observation could possibly be due to nuclear reaction interference effects or might indicate that, in an intermediate step, a neutral isoscalar particle with a mass of 16.70+/ 0.35(stat)+/-0.5(syst) MeV/c^{2} and J^{pi}=1^{+} was created. PMID- 26871325 TI - Electron Localization in Dissociating H_{2}^{+} by Retroaction of a Photoelectron onto Its Source. AB - We investigate the dissociation of H_{2}^{+} into a proton and a H^{0} after single ionization with photons of an energy close to the threshold. We find that the p^{+} and the H^{0} do not emerge symmetrically in the case of the H_{2}^{+} dissociating along the 1ssigma_{g} ground state. Instead, a preference for the ejection of the p^{+} in the direction of the escaping photoelectron can be observed. This symmetry breaking is strongest for very small electron energies. Our experiment is consistent with a recent prediction by Serov and Kheifets [Phys. Rev. A 89, 031402 (2014)]. In their model, which treats the photoelectron classically, the symmetry breaking is induced by the retroaction of the long range Coulomb potential onto the dissociating H_{2}^{+}. PMID- 26871327 TI - Electron Elevator: Excitations across the Band Gap via a Dynamical Gap State. AB - We use time-dependent density functional theory to study self-irradiated Si. We calculate the electronic stopping power of Si in Si by evaluating the energy transferred to the electrons per unit path length by an ion of kinetic energy from 1 eV to 100 keV moving through the host. Electronic stopping is found to be significant below the threshold velocity normally identified with transitions across the band gap. A structured crossover at low velocity exists in place of a hard threshold. An analysis of the time dependence of the transition rates using coupled linear rate equations enables one of the excitation mechanisms to be clearly identified: a defect state induced in the gap by the moving ion acts like an elevator and carries electrons across the band gap. PMID- 26871328 TI - Feshbach-Resonance-Enhanced Coherent Atom-Molecule Conversion with Ultranarrow Photoassociation Resonance. AB - We reveal the existence of high-density Feshbach resonances in the collision between the ground and metastable states of ^{171}Yb and coherently produce the associated Feshbach molecules by photoassociation. The extremely small transition rate is overcome by the enhanced Franck-Condon factor of the weakly bound Feshbach molecule, allowing us to observe Rabi oscillations with long decay time between an atom pair and a molecule in an optical lattice. We also perform the precision measurement of the binding energies, which characterizes the observed resonances. The ultranarrow photoassociation will be a basis for practical implementation of optical Feshbach resonances. PMID- 26871329 TI - Mechanically Mediated Microwave Frequency Conversion in the Quantum Regime. AB - We report the observation of efficient and low-noise frequency conversion between two microwave modes, mediated by the motion of a mechanical resonator subjected to radiation pressure. We achieve coherent conversion of more than 10^{12} photons/s with a 95% efficiency and a 14 kHz bandwidth. With less than 10^{-1} photons.s^{-1}.Hz^{-1} of added noise, this optomechanical frequency converter is suitable for quantum state transduction. We show the ability to operate this converter as a tunable beam splitter, with direct applications for photon routing and communication through complex quantum networks. PMID- 26871330 TI - Quantum Optics Theory of Electronic Noise in Coherent Conductors. AB - We consider the electromagnetic field generated by a coherent conductor in which electron transport is described quantum mechanically. We obtain an input-output relation linking the quantum current in the conductor to the measured electromagnetic field. This allows us to compute the outcome of measurements on the field in terms of the statistical properties of the current. We moreover show how under ac bias the conductor acts as a tunable medium for the field, allowing for the generation of single- and two-mode squeezing through fermionic reservoir engineering. These results explain the recently observed squeezing using normal tunnel junctions [G. Gasse et al., Phys. Rev. Lett. 111, 136601 (2013); J.-C. Forgues et al., Phys. Rev. Lett. 114, 130403 (2015)]. PMID- 26871331 TI - Coherent Population Trapping of a Single Nuclear Spin Under Ambient Conditions. AB - We demonstrate coherent population trapping of a single nuclear spin in a room temperature solid. To this end, we exploit a three-level system with a Lambda configuration in the microwave domain, which consists of nuclear spin states addressed through their hyperfine coupling to the electron spin of a single nitrogen-vacancy defect in diamond. Moreover, the Lambda-scheme relaxation is externally controlled through incoherent optical pumping and separated in time from consecutive coherent microwave excitations. Such a scheme allows us (i) to monitor the sequential accumulation of population into the dark state and (ii) to reach a novel regime of coherent population trapping dynamics for which periodic arrays of dark resonances can be observed, owing to multiple constructive interferences. This Letter offers new prospects for quantum state preparation, information storage in hybrid quantum systems, and metrology. PMID- 26871332 TI - Cavity Light Bullets in Passively Mode-Locked Semiconductor Lasers. AB - We demonstrate the existence of stable three-dimensional dissipative localized structures in the output of a laser coupled to a distant saturable absorber. These phase invariant cavity light bullets are individually addressable and can be envisioned for three-dimensional optical information storage. An effective theory provides for an intuitive picture and allows us to relate their formation to the morphogenesis of static spatial autosolitons and temporal cellular patterns. PMID- 26871333 TI - Universal Nature of the Nonlinear Stage of Modulational Instability. AB - We characterize the nonlinear stage of modulational instability (MI) by studying the longtime asymptotics of the focusing nonlinear Schrodinger (NLS) equation on the infinite line with initial conditions tending to constant values at infinity. Asymptotically in time, the spatial domain divides into three regions: a far left and a far right field, in which the solution is approximately equal to its initial value, and a central region in which the solution has oscillatory behavior described by slow modulations of the periodic traveling wave solutions of the focusing NLS equation. These results demonstrate that the asymptotic stage of MI is universal since the behavior of a large class of perturbations characterized by a continuous spectrum is described by the same asymptotic state. PMID- 26871334 TI - Optical Rogue Waves in Vortex Turbulence. AB - We present a spatiotemporal mechanism for producing 2D optical rogue waves in the presence of a turbulent state with creation, interaction, and annihilation of optical vortices. Spatially periodic structures with bound phase lose stability to phase unbound turbulent states in complex Ginzburg-Landau and Swift-Hohenberg models with external driving. When the pumping is high and the external driving is low, synchronized oscillations are unstable and lead to spatiotemporal vortex mediated turbulence with high excursions in amplitude. Nonlinear amplification leads to rogue waves close to turbulent optical vortices, where the amplitude tends to zero, and to probability density functions (PDFs) with long tails typical of extreme optical events. PMID- 26871335 TI - Optimal Phase-Control Strategy for Damped-Driven Duffing Oscillators. AB - Phase-control techniques of chaos aim to extract periodic behaviors from chaotic systems by applying weak harmonic perturbations with a suitably chosen phase. However, little is known about the best strategy for selecting adequate perturbations to reach desired states. Here we use experimental measures and numerical simulations to assess the benefits of controlling individually the three terms of a Duffing oscillator. Using a real-time analog indicator able to discriminate on-the-fly periodic behaviors from chaos, we reconstruct experimentally the phase versus perturbation strength stability areas when periodic perturbations are applied to different terms governing the oscillator. We verify the system to be more sensitive to perturbations applied to the quadratic term of the double-well Duffing oscillator and to the quartic term of the single-well Duffing oscillator. PMID- 26871336 TI - Optimal Parametric Feedback Excitation of Nonlinear Oscillators. AB - An optimal parametric feedback excitation principle is sought, found, and investigated. The principle is shown to provide an adaptive resonance condition that enables unprecedentedly robust movement generation in a large class of oscillatory dynamical systems. Experimental demonstration of the theory is provided by a nonlinear electronic circuit that realizes self-adaptive parametric excitation without model information, signal processing, and control computation. The observed behavior dramatically differs from the one achievable using classical parametric modulation, which is fundamentally limited by uncertainties in model information and nonlinear effects inevitably present in real world applications. PMID- 26871337 TI - Displacement of an Electrically Charged Drop on a Vibrating Bath. AB - In this work, the manipulation of an electrically charged droplet bouncing on a vertically vibrated bath is investigated. When a horizontal, uniform, and static electric field is applied to it, a motion is induced. The droplet is accelerated when the droplet is small. On the other hand, large droplets appear to move with a constant speed that depends linearly on the applied electrical field. In the latter regime, high-speed imaging of one bounce reveals that the droplet experiences an acceleration due to the electrical force during the flight and decelerates to 0 when interacting with the surface of the bath. Thus, the droplet moves with a constant average speed on a large time scale. We propose a criterion based on the force necessary to move a charged droplet at the surface of the bath to discriminate between constant speed and accelerated droplet regimes. PMID- 26871338 TI - Quantum Radiation Reaction: From Interference to Incoherence. AB - We investigate quantum radiation reaction in laser-electron interactions across different energy and intensity regimes. Using a fully quantum approach which also accounts exactly for the effect of the strong laser pulse on the electron motion, we identify in particular a regime in which radiation reaction is dominated by quantum interference. We find signatures of quantum radiation reaction in the electron spectra which have no classical analogue and which cannot be captured by the incoherent approximations typically used in the high-intensity regime. These signatures are measurable with presently available laser and accelerator technology. PMID- 26871322 TI - Observation of B->D(*) pi^(+)pi^(-)l^(-)nu Decays in e^(+)e^(-) Collisions at the Upsilon(4S) Resonance. AB - We report on measurements of the decays of B- mesons into the semileptonic final states B-->D^(*)pi^(+)pi^(-)l^(-)nu-, where D^(*) represents a D or D^(*) meson and l^(-) is an electron or a muon. These measurements are based on 471*10^(6) BB - pairs recorded with the BABAR detector at the SLAC asymmetric B factory PEP-II. We determine the branching fraction ratios R_{pi^{+}pi^{-}}^{(*)}=B(B[over -] >D^{(*)}pi^{+}pi^{-}l^{-}nu[over -])/B(B[over -]->D^{(*)}l^{-}nu[over -]) using events in which the second B meson is fully reconstructed. We find R_{pi^{+}pi^{ }}=0.067+/-0.010+/-0.008 and R_{pi^{+}pi^{-}}^{*}=0.019+/-0.005+/-0.004, where the first uncertainty is statistical and the second is systematic. Based on these results and assuming isospin invariance, we estimate that B[over -] >D^{(*)}pipil^{-}nu[over -] decays, where pi denotes either a pi^{+/-} and pi^{0} meson, account for up to half the difference between the measured inclusive semileptonic branching fraction to charm hadrons and the corresponding sum of previously measured exclusive branching fractions. PMID- 26871339 TI - Concept of a Contact Spectrum and Its Applications in Atomic Quantum Hall States. AB - A unique feature of ultracold atoms is the separation of length scales, r_{0}?k_{F}^{-1}, where k_{F} and r_{0} are the Fermi momentum characterizing the average particle distance and the range of interaction between atoms, respectively. For s-wave scattering, Shina Tan discovered that such diluteness leads to universal thermodynamic relations governed by contact. Here, we show that the concept of contact can be generalized to an arbitrary partial-wave scattering. Contact of all partial-wave scatterings forms a contact spectrum, which establishes universal thermodynamic relations with notable differences from those in the presence of s-wave scattering alone. Such a contact spectrum is particularly useful for characterizing many-body correlations in atomic quantum Hall states (QHSs). It has an interesting connection with a special bipartite entanglement spectrum of QHSs and enables an intrinsic probe of atomic QHSs using short-range two-body correlations. PMID- 26871340 TI - Thermodynamics of an Attractive 2D Fermi Gas. AB - Thermodynamic properties of matter are conveniently expressed as functional relations between variables known as equations of state. Here we experimentally determine the compressibility, density, and pressure equations of state for an attractive 2D Fermi gas in the normal phase as a function of temperature and interaction strength. In 2D, interacting gases exhibit qualitatively different features to those found in 3D. This is evident in the normalized density equation of state, which peaks at intermediate densities corresponding to the crossover from classical to quantum behavior. PMID- 26871341 TI - Equation of State of Ultracold Fermions in the 2D BEC-BCS Crossover Region. AB - We report the experimental measurement of the equation of state of a two dimensional Fermi gas with attractive s-wave interactions throughout the crossover from a weakly coupled Fermi gas to a Bose gas of tightly bound dimers as the interaction strength is varied. We demonstrate that interactions lead to a renormalization of the density of the Fermi gas by several orders of magnitude. We compare our data near the ground state and at finite temperature with predictions for both fermions and bosons from quantum Monte Carlo simulations and Luttinger-Ward theory. Our results serve as input for investigations of close-to equilibrium dynamics and transport in the two-dimensional system. PMID- 26871342 TI - Cascade of Solitonic Excitations in a Superfluid Fermi gas: From Planar Solitons to Vortex Rings and Lines. AB - We follow the time evolution of a superfluid Fermi gas of resonantly interacting ^{6}Li atoms after a phase imprint. Via tomographic imaging, we observe the formation of a planar dark soliton, its subsequent snaking, and its decay into a vortex ring, which, in turn, breaks to finally leave behind a single solitonic vortex. In intermediate stages, we find evidence for an exotic structure resembling the Phi soliton, a combination of a vortex ring and a vortex line. Direct imaging of the nodal surface reveals its undulation dynamics and its decay via the puncture of the initial soliton plane. The observed evolution of the nodal surface represents dynamics beyond superfluid hydrodynamics, calling for a microscopic description of unitary fermionic superfluids out of equilibrium. PMID- 26871343 TI - Pairing of Fermions with Unequal Effective Charges in an Artificial Magnetic Field. AB - Artificial magnetic fields (AMFs) created for ultracold systems depend sensitively on the internal structure of the atoms. In a mixture, each component experiences a different AMF depending on its internal state. This enables the study of Bardeen-Cooper-Schrieffer pairing of fermions with unequal effective charges. In this Letter, we investigate the superconducting (SC) transition of a system formed by such pairs as a function of field strength. We consider a homogeneous two-component Fermi gas of unequal effective charges but equal densities with attractive interactions. We find that the phase diagram is altered drastically compared to the usual balanced charge case. First, for some AMFs there is no SC transition and isolated SC phases are formed, reflecting the discrete Landau level (LL) structure. SC phases become reentrant both in AMF and temperature. For extremely high fields where both components are confined to their lowest LLs, the effect of the charge imbalance is suppressed. Charge asymmetry reduces the critical temperature even in the low-field semiclassical regime. We discuss a pair breaking mechanism due to the unequal Lorentz forces acting on the components of the Cooper pairs to identify the underlying physics. PMID- 26871344 TI - Apparent First-Order Wetting and Anomalous Scaling in the Two-Dimensional Ising Model. AB - The global phase diagram of wetting in the two-dimensional Ising model is obtained through the exact calculation of the surface excess free energy. In addition to a surface field for inducing wetting, a surface-coupling enhancement is also included. The wetting transition (of second order) is critical for any finite ratio of surface coupling J_{s} to bulk coupling J, and becomes of first order in the limit J_{s}/J->infinity. However, for J_{s}/J?1, the critical region is exponentially small and is practically invisible to numerical studies. A distinct preasymptotic regime exists in which the transition displays first-order character. In this regime, surprisingly, the surface susceptibility and surface specific heat develop a divergence and show anomalous scaling with an exponent equal to 3/2. PMID- 26871345 TI - Chern Kondo Insulator in an Optical Lattice. AB - We propose to realize and observe Chern Kondo insulators in an optical superlattice with laser-assisted s and p orbital hybridization and a synthetic gauge field, which can be engineered based on the recent cold atom experiments. Considering a double-well square optical lattice, the localized s orbitals are decoupled from itinerant p bands and are driven into a Mott insulator due to the strong Hubbard interaction. Raman laser beams are then applied to induce tunnelings between s and p orbitals, and generate a staggered flux simultaneously. Because of the strong Hubbard interaction of s orbital states, we predict the existence of a critical Raman laser-assisted coupling, beyond which the Kondo screening is achieved, and then a fully gapped Chern Kondo phase emerges, with the topology characterized by integer Chern numbers. Being a strongly correlated topological state, the Chern Kondo phase is different from the single-particle quantum anomalous Hall state, and can be identified by measuring the band topology and double occupancy of s orbitals. The experimental realization and detection of the predicted Chern Kondo insulator are also proposed. PMID- 26871346 TI - Kibble-Zurek Mechanism in Topologically Nontrivial Zigzag Chains of Polariton Micropillars. AB - We consider a zigzag chain of coupled micropillar cavities, taking into account the polarization of polariton states. We show that the TE-TM splitting of photonic cavity modes yields topologically protected polariton edge states. During the strongly nonadiabatic process of polariton condensation, the Kibble Zurek mechanism leads to a random choice of polarization, equivalent to the dimerization of polymer chains. We show that dark-bright solitons appear as domain walls between polarization domains, analogous to the Su-Schrieffer-Heeger solitons in polymers. The soliton density scales as a power law with respect to the quenching parameter. PMID- 26871347 TI - Kondo Breakdown and Quantum Oscillations in SmB_{6}. AB - Recent quantum oscillation experiments on SmB_{6} pose a paradox, for while the angular dependence of the oscillation frequencies suggest a 3D bulk Fermi surface, SmB_{6} remains robustly insulating to very high magnetic fields. Moreover, a sudden low temperature upturn in the amplitude of the oscillations raises the possibility of quantum criticality. Here we discuss recently proposed mechanisms for this effect, contrasting bulk and surface scenarios. We argue that topological surface states permit us to reconcile the various data with bulk transport and spectroscopy measurements, interpreting the low temperature upturn in the quantum oscillation amplitudes as a result of surface Kondo breakdown and the high frequency oscillations as large topologically protected orbits around the X point. We discuss various predictions that can be used to test this theory. PMID- 26871323 TI - Measurement of Azimuthal Asymmetries in Inclusive Charged Dipion Production in e^{+}e^{-} Annihilations at sqrt[s]=3.65 GeV. AB - We present a measurement of the azimuthal asymmetries of two charged pions in the inclusive process e^{+}e^{-}->pipiX, based on a data set of 62 pb^{-1} at the center-of-mass energy of 3.65 GeV collected with the BESIII detector. These asymmetries can be attributed to the Collins fragmentation function. We observe a nonzero asymmetry, which increases with increasing pion momentum. As our energy scale is close to that of the existing semi-inclusive deep inelastic scattering experimental data, the measured asymmetries are important inputs for the global analysis of extracting the quark transversity distribution inside the nucleon and are valuable to explore the energy evolution of the spin-dependent fragmentation function. PMID- 26871349 TI - Anomalous Coulomb Drag in Electron-Hole Bilayers due to the Formation of Excitons. AB - Several recent experiments have reported an anomalous temperature dependence of the Coulomb drag effect in electron-hole bilayers. Motivated by these puzzling data, we study theoretically a low-density electron-hole bilayer, where electrons and holes avoid quantum degeneracy by forming excitons. We describe the ionization-recombination crossover between the electron-hole plasma and exciton gas and calculate both the intralayer and drag resistivity as a function of temperature. The latter exhibits a minimum followed by a sharp upturn at low temperatures, in qualitative agreement with the experimental observations [see, e.g., J. A. Seamons et al., Phys. Rev. Lett. 102, 026804 (2009)]. Importantly, the drag resistivity in the proposed scenario is found to be rather insensitive to a mismatch in electron and hole concentrations, in sharp contrast to the scenario of electron-hole Cooper pairing. PMID- 26871348 TI - Quantum Oscillation in Narrow-Gap Topological Insulators. AB - The canonical understanding of quantum oscillation in metals is challenged by the observation of the de Haas-van Alphen effect in an insulator, SmB_{6} [Tan et al, Science 349, 287 (2015)]. Based on a two-band model with inverted band structure, we show that the periodically narrowing hybridization gap in magnetic fields can induce the oscillation of low-energy density of states in the bulk, which is observable provided that the activation energy is small and comparable to the Landau level spacing. Its temperature dependence strongly deviates from the Lifshitz-Kosevich theory. The nontrivial band topology manifests itself as a nonzero Berry phase in the oscillation pattern, which crosses over to a trivial Berry phase by increasing the temperature or the magnetic field. Further predictions to experiments are also proposed. PMID- 26871350 TI - Quantum Dephasing in a Gated GaAs Triple Quantum Dot due to Nonergodic Noise. AB - We extract the phase coherence of a qubit defined by singlet and triplet electronic states in a gated GaAs triple quantum dot, measuring on time scales much shorter than the decorrelation time of the environmental noise. In this nonergodic regime, we observe that the coherence is boosted and several dephasing times emerge, depending on how the phase stability is extracted. We elucidate their mutual relations, and demonstrate that they reflect the noise short-time dynamics. PMID- 26871351 TI - Quantum Transport and Observation of Dyakonov-Perel Spin-Orbit Scattering in Monolayer MoS_{2}. AB - Monolayers of group 6 transition metal dichalcogenides are promising candidates for future spin-, valley-, and charge-based applications. Quantum transport in these materials reflects a complex interplay between real spin and pseudospin (valley) relaxation processes, which leads to either positive or negative quantum correction to the classical conductivity. Here we report experimental observation of a crossover from weak localization to weak antilocalization in highly n-doped monolayer MoS_{2}. We show that the crossover can be explained by a single parameter associated with electron spin lifetime of the system. At low temperatures and high carrier densities, the spin lifetime is inversely proportional to momentum relaxation time; this indicates that spin relaxation occurs via a Dyakonov-Perel mechanism. PMID- 26871352 TI - Magnetostriction and Magnetostructural Domains in Antiferromagnetic YBa2Cu3O6. AB - We use high-resolution neutron Larmor diffraction and capacitative dilatometry to investigate spontaneous and forced magnetostriction in undoped, antiferromagnetic YBa_{2}Cu_{3}O_{6.0}, the parent compound of a prominent family of high temperature superconductors. Upon cooling below the Neel temperature T_{N}=420 K, Larmor diffraction reveals the formation of magnetostructural domains of characteristic size ~240 nm. In the antiferromagnetic state, dilatometry reveals a minute (4*10^{-6}) orthorhombic distortion of the crystal lattice in external magnetic fields. We attribute these observations to exchange striction and spin orbit coupling induced magnetostriction, respectively, and show that they have an important influence on the thermal and charge transport properties of undoped and lightly doped cuprates. PMID- 26871353 TI - Anisotropic Absorption of Pure Spin Currents. AB - Spin transfer in magnetic multilayers offers the possibility of ultrafast, low power device operation. We report a study of spin pumping in spin valves, demonstrating that a strong anisotropy of spin pumping from the source layer can be induced by an angular dependence of the total Gilbert damping parameter, alpha, in the spin sink layer. Using lab- and synchrotron-based ferromagnetic resonance, we show that an in-plane variation of damping in a crystalline Co_{50}Fe_{50} layer leads to an anisotropic alpha in a polycrystalline Ni_{81}Fe_{19} layer. This anisotropy is suppressed above the spin diffusion length in Cr, which is found to be 8 nm, and is independent of static exchange coupling in the spin valve. These results offer a valuable insight into the transmission and absorption of spin currents, and a mechanism by which enhanced spin torques and angular control may be realized for next-generation spintronic devices. PMID- 26871354 TI - Complex Field-Induced States in Linarite PbCuSO4(OH)2 with a Variety of High Order Exotic Spin-Density Wave States. AB - Low-temperature neutron diffraction and NMR studies of field-induced phases in linarite are presented for magnetic fields H?b axis. A two-step spin-flop transition is observed, as well as a transition transforming a helical magnetic ground state into an unusual magnetic phase with sine-wave-modulated moments ?H. An effective J[over ~]_{1}-J[over ~]_{2} single-chain model with a magnetization dependent frustration ratio alpha_{eff}=-J[over ~]_{2}/J[over ~]_{1} is proposed. The latter is governed by skew interchain couplings and shifted to the vicinity of the ferromagnetic critical point. It explains qualitatively the observation of a rich variety of exotic longitudinal collinear spin-density wave, SDW_{p}, states (9>=p>=2). PMID- 26871355 TI - Spatial Evolution of the Ferromagnetic Phase Transition in an Exchange Graded Film. AB - A combination of experiments and numerical modeling was used to study the spatial evolution of the ferromagnetic phase transition in a thin film engineered to have a smooth gradient in exchange strength. Mean-field simulations predict, and experiments confirm, that a 100 nm Ni_{x}Cu_{1-x} alloy film with Ni concentration that varies by 9% as a function of depth behaves predominantly as if composed of a continuum of uncoupled ferromagnetic layers with continuously varying Curie temperatures. A mobile boundary separating ordered and disordered regions emerges as the temperature is increased. We demonstrate continuous control of the boundary position with temperature, and reversible control of the magnetization on both sides of the boundary with the magnetic field. PMID- 26871356 TI - Parametric Harmonic Generation as a Probe of Unconstrained Spin Magnetization Precession in the Shallow Barrier Limit. AB - We study the parametric excitation of high orders of magnetization precession in ultrathin films having perpendicular magnetic anisotropy. We observe that for a given driving field amplitude the harmonic generation can be increased by lowering the barrier with the application of an in-plane magnetic field in the manner of the Smit-Beljers effect. In this effect, the magnetic stiffness is reduced not by lowering the magnitude of the magnetic field upon which the spins precess, but rather by effectively releasing the field's "anchoring" point. This results in a shallow energy barrier where the electrons' spin is locally unconstrained. While the observation is unveiled in the form of nonlinear high harmonic generation, we believe that the physics whereby the barrier is suppressed by an external magnetic field may apply to other phenomena associated with ultrathin films. In these cases, such unconstrained motion may serve as a sensitive probe of the torques associated with proximate spin currents. Moreover, our approach may be used as a model system for the study of phase transitions in the field of nonlinear dynamics. PMID- 26871357 TI - Density Shock Waves in Confined Microswimmers. AB - Motile and driven particles confined in microfluidic channels exhibit interesting emergent behavior, from propagating density bands to density shock waves. A deeper understanding of the physical mechanisms responsible for these emergent structures is relevant to a number of physical and biomedical applications. Here, we study the formation of density shock waves in the context of an idealized model of microswimmers confined in a narrow channel and subject to a uniform external flow. Interestingly, these density shock waves exhibit a transition from "subsonic" with compression at the back to "supersonic" with compression at the front of the population as the intensity of the external flow increases. This behavior is the result of a nontrivial interplay between hydrodynamic interactions and geometric confinement, and it is confirmed by a novel quasilinear wave model that properly captures the dependence of the shock formation on the external flow. These findings can be used to guide the development of novel mechanisms for controlling the emergent density distribution and the average population speed, with potentially profound implications on various processes in industry and biotechnology, such as the transport and sorting of cells in flow channels. PMID- 26871358 TI - Solvent Role in the Formation of Electric Double Layers with Surface Charge Regulation: A Bystander or a Key Participant? AB - The charge formation at interfaces involving electrolyte solutions is due to the chemical equilibrium between the surface reactive groups and the potential determining ions in the solution (i.e., charge regulation). In this Letter we report our findings that this equilibrium is strongly coupled to the precise molecular structure of the solution near the charged interface. The neutral solvent molecules dominate this structure due to their overwhelmingly large number. Treating the solvent as a structureless continuum leads to a fundamentally inadequate physical picture of charged interfaces. We show that a proper account of the solvent effect leads to an unexpected and complex system behavior that is affected by the molecular and ionic excluded volumes and van der Waals interactions. PMID- 26871359 TI - Probing the Role of Mobility in the Collective Motion of Nonequilibrium Systems. AB - By systematically varying the mobility of self-propelled particles in a 2D lattice, we experimentally study the influence of particle mobility on system's collective motion. Our system is intrinsically nonequilibrium due to the lack of energy equipartition. By constructing the covariance matrix of spatial fluctuations and solving for its eigenmodes, we obtain the collective motions of the system with various magnitudes. Interestingly, our structurally ordered nonequilibrium system exhibits properties almost identical to disordered glassy systems under thermal equilibrium: the modes with large overall motions are spatially correlated and quasilocalized while the modes with small collective motions are highly localized, resembling the low- and high-frequency modes in glass. More surprisingly, a peak similar to the boson peak forms in our nonequilibrium system as the number of mobile particles increases, revealing the possible origin of the boson peak from a dynamic aspect. We further illustrate that the spatially correlated large-movement modes can be produced by the cooperation of highly active particles above a threshold fraction, while the localized small-movement modes can be created by adding individual inactive particles. Our study clarifies the role of mobility in collective motions, and further suggests a promising possibility of extending the powerful mode analysis approach to nonequilibrium systems. PMID- 26871360 TI - Erratum: Vanishing Quantum Discord is Necessary and Sufficient for Completely Positive Maps [Phys. Rev. Lett. 102, 100402 (2009)]. PMID- 26871361 TI - Erratum: Strong Monogamy Conjecture for Multiqubit Entanglement: The Four-Qubit Case [Phys. Rev. Lett. 113, 110501 (2014)]. PMID- 26871362 TI - Erratum: Topological Jamming of Spontaneously Knotted Polyelectrolyte Chains Driven through a Nanopore [Phys. Rev. Lett. 109, 118301 (2012)]. PMID- 26871367 TI - OX130 Monoclonal Antibody Recognizes Human SIRPbeta1 but Cross-Reacts on SIRPalpha from One Allele. AB - The SIRP family of myeloid-paired receptors are characterized by having both activating and inhibiting members with extracellular regions that are relatively similar. Making good reagents to these receptors is not straightforward, particularly as they are relatively polymorphic. We describe the production of a monoclonal antibody (MAb) called OX130 that recognizes both common alleles of the human activating SIRPbeta1 receptor but also cross-reacts with one of the common alleles of the inhibitory human SIRPalpha receptor. Thus one might get different outcomes when this MAb is used in assays from different individuals and shows the importance of characterizing SIRP MAb in this way. PMID- 26871368 TI - Fusion genes in malignant neoplastic disorders of haematopoietic system. AB - OBJECTIVES: The new World Health Organization's (WHO) classification of haematopoietic and lymphoid tissue neoplasms incorporating the recurrent fusion genes as the defining criteria for different haematopoietic malignant phenotypes is reviewed. The recurrent fusion genes incorporated in the new WHO's classification and other chromosomal rearrangements of haematopoietic and lymphoid tissue neoplasms are reviewed. METHODOLOGY: Cytokines and transcription factors in haematopoiesis and leukaemic mechanisms are described. Genetic features and clinical implications due to the encoded chimeric neoproteins causing malignant haematopoietic disorders are reviewed. RESULTS AND DISCUSSION: Multiple translocation partner genes are well known for leukaemia such as MYC, MLL, RARA, ALK, and RUNX1. With the advent of more sophisticated diagnostic tools and bioinformatics algorithms, an exponential growth in fusion genes discoveries is likely to increase. CONCLUSION: Demonstration of fusion genes and their specific translocation breakpoints in malignant haematological disorders are crucial for understanding the molecular pathogenesis and clinical phenotype of cancer, determining prognostic indexes and therapeutic responses, and monitoring residual disease and relapse status. PMID- 26871369 TI - Pharmacogenetics of Cytochrome P450 Enzymes in American Indian and Caucasian Children Admitted to a Psychiatric Hospital. AB - OBJECTIVE: The cytochrome P450 (CYP450) enzyme system metabolizes many psychiatric medications. We compare frequencies of alleles and phenotypes for CYP2D6, CYP2C9, and CYP2C19 in American Indian (AI) and Caucasian youth treated at a psychiatric hospital in the Northwestern United States. METHODS: A retrospective chart review evaluated CYP450 pharmacogenetic (PGx) data from the Shodair Children's Hospital Clinical Genetic Laboratory between 2006 and 2014. CYP2D6 genotyping was performed using the xTAG(r) CYP2D6 Kit (Luminex, Austin, TX). CYP2C9 and CYP2C19 genotyping was performed by laboratory-developed assays using allele-specific quantitative polymerase chain reaction (qPCR) and/or melt curve analysis. RESULTS: A total of 123 AIs and 688 Caucasians met criteria for inclusion. The overall prevalence of CYP2D6 poor metabolizers was 8.3% (95% Confidence Interval [CI] 6.1%, 10.4%), 9.3% in Caucasians (95% CI 7.1%, 11.5%), and 2.4% in AIs (95% CI 0%, 5.2%). The overall prevalence of CYP2D6 ultrarapid metabolizers was 1.6% (95% CI 0.7%, 2.5%), 1.6% in the Caucasians (95% CI 0.7%, 2.5%), and 1.6% in AIs (95% CI 0%, 3.9%). The overall prevalence of CYP2C9 poor metabolizers was 3% (95% CI 1.7%, 4.2%), 3.2% in Caucasians (95% CI 1.8%, 4.6%), and 1.8% in AIs (95% CI 0%, 4.2%). The overall prevalence of CYP2C19 poor metabolizers was 2.5% (95% CI 1.3%, 3.6%), 2.9% in Caucasians (95% CI 1.6%, 4.2%), and 0% in AIs. The overall prevalence of CYP2C19 ultrarapid metabolizers was 1.5% (95% CI 0.6%, 2.4%), 1.6% in Caucasians (95% CI 0.6%, 2.6%), and 0.9% in AIs (95% CI 0%, 2.6%). CONCLUSIONS: This study is the first to identify differences in polymorphism frequencies of the CYP450 system in AIs and Caucasian youth admitted to a psychiatric hospital. Our findings warrant further study of these populations to determine if these differences are generalizable to the larger population of Caucasian and AI/Alaska Native youth in the Northwestern United States. PMID- 26871370 TI - Erratum. PMID- 26871372 TI - A specific nanomanufacturing challenge. AB - For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO((r)) brick scaled down by a factor of 10(n) for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts. PMID- 26871373 TI - Letter to the Editor: A paradigm shift toward MRI-guided and MRI-verified DBS surgery. PMID- 26871371 TI - Perceptions of pharmacogenetic research to guide tobacco cessation by patients, providers and leaders in a tribal healthcare setting. AB - AIM: Describe patients,' providers' and healthcare system leaders' perceptions of pharmacogenetic research to guide tobacco cessation treatment in an American Indian/Alaska Native primary care setting. MATERIALS & METHODS: This qualitative study used semistructured interviews with 20 American Indian/Alaska Native current or former tobacco users, 12 healthcare providers and nine healthcare system leaders. RESULTS: Participants supported pharmacogenetic research to guide tobacco cessation treatment provided that a community-based participatory research approach be employed, research closely coordinate with existing tobacco cessation services and access to pharmacogenetic test results be restricted to providers involved in tobacco cessation. CONCLUSION: Despite a history of mistrust toward genetic research in tribal communities, participants expressed willingness to support pharmacogenetic research to guide tobacco cessation treatment. PMID- 26871374 TI - Clinical outcomes of middle fossa craniotomy for superior semicircular canal dehiscence repair. AB - OBJECTIVE Superior semicircular canal dehiscence (SSCD) is a rare disorder characterized by the formation of a third opening in the inner ear between the superior semicircular canal and the middle cranial fossa. Aberrant communication through this opening causes a syndrome of hearing loss, pulsatile tinnitus, disequilibrium, and autophony. This study analyzed the clinical outcomes of a single-institution series of patients with SSCD undergoing surgical repair by the same otolaryngologist and neurosurgeon. METHODS All patients who underwent SSCD repair at the University of California, Los Angeles, between March 2011 and November 2014 were included. All patients had their SSCD repaired via middle fossa craniotomy by the same otolaryngologist and neurosurgeon. Outcomes were analyzed with Fisher's exact test. RESULTS A total of 18 patients with a mean age of 56.2 years (range 27-84 years) and an average follow-up of 5.0 months (range 0.2-21.8 months) underwent 21 cases of SSCD repair. Following treatment, all patients (100%) reported resolution in >= 1 symptom associated with SSCD. Autophony (p = 0.0005), tinnitus (p = 0.0059), and sound- and/or pressure-induced dizziness (p = 0.0437) showed significant symptomatic resolution. Following treatment, 29% (2/7) of patients developed imbalance, 20% (1/5) of patients developed sound- and/or pressure-induced dizziness, and 18% (2/11) of patients developed aural fullness. Among patients with improved symptoms following surgical repair, none reported recurrence of symptoms at subsequent follow-up visits. CONCLUSIONS SSCD remains an underdiagnosed and undertreated condition. Surgical repair of SSCD using a middle fossa craniotomy is associated with a high rate of symptom resolution. Continued investigation using a larger patient cohort and longer-term follow-up could further demonstrate the effectiveness of using middle fossa craniotomy for SSCD repair. PMID- 26871375 TI - Virtual and stereoscopic anatomy: when virtual reality meets medical education. AB - OBJECTIVE The authors sought to construct, implement, and evaluate an interactive and stereoscopic resource for teaching neuroanatomy, accessible from personal computers. METHODS Forty fresh brains (80 hemispheres) were dissected. Images of areas of interest were captured using a manual turntable and processed and stored in a 5337-image database. Pedagogic evaluation was performed in 84 graduate medical students, divided into 3 groups: 1 (conventional method), 2 (interactive nonstereoscopic), and 3 (interactive and stereoscopic). The method was evaluated through a written theory test and a lab practicum. RESULTS Groups 2 and 3 showed the highest mean scores in pedagogic evaluations and differed significantly from Group 1 (p < 0.05). Group 2 did not differ statistically from Group 3 (p > 0.05). Size effects, measured as differences in scores before and after lectures, indicate the effectiveness of the method. ANOVA results showed significant difference (p < 0.05) between groups, and the Tukey test showed statistical differences between Group 1 and the other 2 groups (p < 0.05). No statistical differences between Groups 2 and 3 were found in the practicum. However, there were significant differences when Groups 2 and 3 were compared with Group 1 (p < 0.05). CONCLUSIONS The authors conclude that this method promoted further improvement in knowledge for students and fostered significantly higher learning when compared with traditional teaching resources. PMID- 26871376 TI - Letter to the Editor: Cadaveric CSF reconstitution model for neuroendoscopic intraventricular procedures. PMID- 26871377 TI - Letter to the Editor: Last call for clipping aneurysms? PMID- 26871379 TI - Benefits and Enjoyment of a Swimming Intervention for Youth With Cerebral Palsy: An RCT Study. AB - PURPOSE: To investigate enjoyment and specific benefits of a swimming intervention for youth with cerebral palsy (CP). METHODS: Fourteen youth with CP (aged 7 to 17 years, Gross Motor Function Classification System levels I to III) were randomly assigned to control and swimming groups. Walking ability, swimming skills, fatigue, and pain were assessed at baseline, after a 10-week swimming intervention (2/week, 40-50 minutes) or control period, after a 5-week follow-up and, for the intervention group, after a 20-week follow-up period. The level of enjoyment of each swim-session was assessed. RESULTS: Levels of enjoyment were high. Walking and swimming skills improved significantly more in the swimming than in the control group (P = .043; P = .002, respectively), whereas fatigue and pain did not increase. After 20 weeks, gains in walking and swimming skills were retained (P = .017; P = .016, respectively). CONCLUSION: We recommend a swimming program for youth with CP to complement a physical therapy program. PMID- 26871380 TI - Hope may not be the best component of an exercise regimen. PMID- 26871378 TI - Russell Meyers (1905-1999): pioneer of functional and ultrasonic neurosurgery. AB - Advances in functional neurosurgery, including neuromodulation and more recently ultrasonic ablation of basal ganglia structures, have improved the quality of life for patients with debilitating movement disorders. What is little known, however, is that both of these neurosurgical advances, which remain on the cutting edge, have their origin in the pioneering work of Russell Meyers, whose contributions are documented in this paper. Meyers' published work and professional correspondence are reviewed, in addition to documents held by the Department of Neurosurgery at the University of Iowa. Meyers was born in Brooklyn, New York, and received his neurosurgical training at hospitals in New York City under Jefferson Browder. In 1939, a chance encounter with a young woman with damaged bilateral ventral striata convinced Meyers that the caudate could be resected to treat Parkinsonism without disrupting consciousness. Shortly thereafter, he performed the first caudate resection for postencephalitic Parkinsonism. In 1946, Meyers became the first chairman of neurosurgery at the State University of Iowa (now the University of Iowa), which led to the recruitment of 8 faculty members and the training of 18 residents during his tenure (1946-1963). Through collaboration with the Fry brothers at the University of Illinois, Meyers performed the first stereotactic ultrasonic ablations of deep brain structures to treat tremor, choreoathetosis, dystonia, intractable pain, and hypothalamic hamartoma. Meyers left academic neurosurgery in 1963 for reasons that are unclear, but he continued clinical neurosurgery work for several more years. Despite his early departure from academic medicine, Meyers' contributions to functional neurosurgery provided a lasting legacy that has improved the lives of many patients with movement disorders. PMID- 26871381 TI - Bulldog scalp. PMID- 26871382 TI - A 60-year-old man with forehead swelling. PMID- 26871383 TI - Can patients opt to turn off implantable cardioverter-defibrillators near the end of life? PMID- 26871384 TI - The ethics of ICDs: History and future directions. PMID- 26871385 TI - Veterans, guilt, and suicide risk: An opportunity to collaborate with chaplains? PMID- 26871386 TI - Many shades of guilt. PMID- 26871387 TI - A tale of two sisters with liver disease. PMID- 26871388 TI - Common neurologic emergencies for nonneurologists: When minutes count. AB - Neurologic emergencies arise frequently and, if not diagnosed and treated quickly, can have devastating results, with high rates of long-term disability and death. Prompt recognition is an important skill. This article provides detailed analyses of acute stroke, subarachnoid hemorrhage, status epilepticus, and other neurologic emergencies for physicians who are not neurologists. PMID- 26871389 TI - The intersection of obstructive lung disease and sleep apnea. AB - Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have synergistic detrimental effects. Their comorbid association leads to compromised gas exchange (hypoxia and hypercapnia) and higher rates of morbidity and death. As our understanding of the pathophysiologic processes of sleep evolves, the relationship between OSA and obstructive lung diseases such as COPD ("overlap syndrome") or asthma ("alternative overlap syndrome") has become more apparent. The pathophysiology of the combined conditions and optimal management are still being defined, but the effect on quality of life and morbidity underscore the importance of proper diagnosis and appropriately tailored management in these patients. PMID- 26871390 TI - Prescribing exercise to help your patients lose weight. AB - Exercise, in conjunction with diet, is critical to losing weight and maintaining health in obese patients. While it can be challenging for an obese person to transition to a healthy lifestyle, the physical and emotional benefits of a regular exercise program make it worth the effort. PMID- 26871391 TI - Patient information: Obesity and exercise. PMID- 26871393 TI - Venous hemodynamic improvement after endovenous radiofrequency ablation of saphenous varicose veins. AB - BACKGROUND: Endovenous radiofrequency ablation (RFA) has been a viable treatment option for patients with saphenous varicose veins. The purpose of our study was to assess venous hemodynamic change before and after RFA by using air plethysmography (APG). METHODS: We prospectively analyzed the data of consecutive 91 patients with 124 limbs who underwent RFA for primary varicose veins. Overall venous hemodynamics of the limb was assessed using APG. The Venous Filling Index (VFI) was determined as a measure of reflux (normal range, <2 mL). Duplex scanning were performed to evaluate saphenous vein occlusion, deep venous thrombus and endovenous heat-induced thrombosis (EHIT). RESULTS: The VFI were significantly reduced from 4.1+/-3.1 preoperatively to 1.4+/-1.0, 1.3+/-0.8 and 1.4+/-1.2 at 1 week, 1 month and 4 month postoperatively, respectively. The percentage of the VFI >2 mL/s was 77% preoperatively, while it significantly decreased to 17%, 16%, and 18% at 1 week, 1 month, and 4 month postoperatively, respectively. Duplex scanning showed 100% of saphenous vein occlusion and no significant EHIT II-IV. CONCLUSIONS: Correction or significant improvement of venous reflux was achieved by RFA. Together with duplex scanning findings, RFA is a safe and hemodynamically effective treatment for varicose veins. PMID- 26871392 TI - Transcutaneous oxygen pressure as a surrogate index of lower limb amputation. AB - INTRODUCTION: A large number of clinical trials of therapeutic angiogenesis in patients with critical limb ischemia have been conducted in recent years. However, limb amputation, which is used as a primary endpoint in such studies, is not often required in Japan, which can make it difficult to carry out related clinical trials. Transcutaneous oxygen pressure (TcPO2) is widely used to evaluate the severity of limb ischemia, to decide the level of amputation, and to predict wound healing after limb amputation. The aim of the present study was to elucidate whether TcPO2 can be a surrogate index of limb ischemia, and to define an appropriate cutoff value for wound healing after limb amputation using meta analysis. EVIDENCE ACQUISITION: A computer search was performed to identify studies describing the association between TcPO2 and limb ischemic events. From these, studies focused on wound healing after limb amputation were combined and analyzed. EVIDENCE SYNTHESIS: Eleven studies were identified for inclusion in this analysis. The analysis demonstrated that TcPO2 20 mmHg was a valid cutoff value for limb amputation and TcPO2 30 mmHg would be an appropriate value for wound healing after limb amputation. CONCLUSIONS: TcPO2 of 20 and 30 mmHg were considered appropriate cutoff values for limb amputation and wound healing after amputation, respectively. PMID- 26871394 TI - Baroreflex sensitivity and carotid intima-media thickness in risk stratification of prehypertensives and hypertensives. AB - BACKGROUND? The aim of the study was to evaluate the clinical significance of baroreflex sensitivity (BRS) and carotid intima media thickness (IMT) in risk stratification of hypertensives and subjects with high normal blood pressure (SHNBP). METHODS? A total of 20 patients (61+/-13 years of age, 10 female/10 male) with essential, treated hypertension and 20 subjects (59+/-8 years of age, 10 female/10 male) with high normal blood pressure were enrolled. The interrelationship between BRS expressed in ms/mmHg (BRS) and IMT of common carotid artery (CCA) in hypertensives and subjects with high normal blood pressure (SHNBP, prehypertensives) was evaluated. BRS was determined by the sequence and spectral method: a five-minute non-invasive beat-to-beat recording of blood pressure (BP) and R-R interval with use of Collin CBM-7000 monitor, controlled breathing at a frequency of 0.1 Hz. Duplex ultrasonographic examination of the carotid wall and IMT of both CCA and carotid bulb were performed in all patients. RESULTS? Essential hypertension was associated with decreased BRS (r =-0.53, P<0.001). We found out that there was no significant difference between BRS and IMT CCA values in mild treated hypertensives and those in SHNBP. This finding was independent of age-dependent decrease of BRS. SHNBP and hypertensives with critical value BRS<=5 ms/mmHg have significantly increased IMT CCA. CONCLUSIONS? Decreased BRS is an early sign of autonomic dysfunction even in prehypertensive period. SHNBP and hypertensives with BRS<=5ms/mmHg have significantly increased IMT CCA. The principal result of this study showed that BRS and carotid IMT in relatively low-risk hypertensives and SHNBP could identify subjects at higher cardiovascular risk. PMID- 26871395 TI - Histologic and sonographic features of holmium laser in the treatment of chronic venous disease. AB - BACKGROUND: A new holmium laser (HOL) has been introduced to the market. The device is able to reduce the great saphenous vein (GSV) caliber in a tumescence free procedure, favoring an effective sclerotherapy of large vessels. Aim of the present investigation is to provide the first in vivo data about the effect of HOL on GSV histology. METHODS: Six chronic venous disease (C2-5, Ep, As, Pr) patients (M:F ratio 1:1; age: 57+/-8, BMI 24+/-2 kg/m2) underwent HOL-assisted caliber reduction of the GSV, high-ligation and flush ligation of the incompetent tributaries. Three cm of proximal great saphenous vein not treated by laser and 3 cm of a contiguous segment that was just previously treated by HOL were harvested. Histological assessments were performed. Patent GSV lumen caliber was assessed at the mid-thigh right before, and after the procedure. Periprocedural pain was graded by Visual Analogue Scale. RESULTS: GSV samples after holmium laser therapy showed thickening of the vascular wall with a decreased, yet patent lumen. Immunostaining demonstrated intact endothelial lining in both the treated and not treated segments. Expansion of collagen fibers was observed in the laser treated segments. Collagen appeared more homogeneous than in controls, with an amorphous appearance. Laser treated veins showed a reduction in elastic fibers with greater fragmentation. Smooth muscle cells appeared swollen. The caliber of the mid-thigh great saphenous vein lumen decreased from 8.1+/-0.8 mm to 3.9+/-0.2 mm (P<0.0001). The average periprocedural pain was 1+/-0.6. CONCLUSIONS: HOL significantly reduces the caliber of the GSV. The endothelial lining is spared, while the remaining wall is thickened by a hyalinization-like process. PMID- 26871396 TI - Prevalence of metabolic syndrome in patients undergoing total joint arthroplasty and relevance of biomarkers. AB - BACKGROUND: Metabolic syndrome (MetS) is a collection of clinical conditions, including central obesity, hypertension, glucose intolerance and dyslipidemia. The long-term inflammatory and metabolic dysfunction associated with MetS may contribute to osteoarthritic processes leading up to total joint arthroplasty (TJA). The purpose of this study was to investigate levels of metabolic biomarkers and the prevalence of MetS in patients undergoing TJA. METHODS: Under IRB approval, citrated plasma samples were collected from 41 patients undergoing total hip and knee arthroplasty (THA/TKA) preoperatively and day 1 postoperatively. Control group consisted of 25 healthy human plasma samples (female and male, 18-35 years old) purchased from George King Biomedical Inc. (Overland Park, KS, USA). Samples were profiled for c-peptide, ferritin, IL-6, insulin, resistin, TNF-alpha, IL-1a, leptin, and PAI-1 using metabolic biochips purchased from RANDOX Co. (Antrim, Northern Ireland). NCEP/ATP III guidelines were used to evaluate which patients met MetS criteria. RESULTS: Levels of IL-6, resistin, TNF-a, IL-1a, leptin, and PAI-1 were significantly elevated in patients undergoing TJA compared to normal. C-peptide and insulin were both decreased in TJA compared to normal. No significance was found when comparing TJA to normal for ferritin. TNFalpha was significantly lower in TJA+MetS compared to TJA-MetS, while other biomarkers showed no difference in TJA+/-MetS populations. Insulin & c-peptide both showed a significant decrease in TJA-MetS compared to normal, but levels in TJA+MetS patients were not significantly different from controls. Resistin showed significant increases in TJA+MetS vs. normal, but not in TJA-MetS vs. normal. CONCLUSIONS: Overall, the differing metabolic profile seen in patients undergoing TJA suggest ongoing metabolic dysfunction. Insulin and c peptide patterns among the different test groups hint toward a complex and dysfunctional metabolic process involved, with leptin and underlying insulin resistance playing a role. Increased resistin in TJA+MetS, but not in TJA-MetS, compared to normal, suggests that while elevated resistin levels may be associated with the osteoarthritic process, levels are further attenuated by MetS, which is highly prevalent in this population. Increased TNFalpha in TJA MetS compared to TJA+MetS may be an artifact of differing sample populations or a true complication of the complex pathophysiology and medical regimen seen in patients with both OA and MetS. The lack of difference seen in the remaining biomarkers suggest that having MetS as a comorbidity does not contribute to the elevated levels seen in patients undergoing TJA. PMID- 26871397 TI - Human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease. AB - BACKGROUND: Specific monocyte and macrophage subsets have been implicated in atherosclerosis, with intermediate monocytes proportionally elevated in cardiovascular disease and M1 macrophages abundant in unstable atherosclerotic plaques. While several studies have shown altered proportions of these subsets in atherosclerosis, studies examining functional and phenotypic subset alterations remain scarce. METHODS: We used whole blood flow cytometry to investigate the expression of M1 (CD86) and M2 (CD163) markers on monocyte subsets of atherosclerotic patients and controls. RESULTS: Atherosclerotic patients had a more inflammatory monocyte profile than controls, indicated by increased intermediate subset proportions, a higher classical monocyte CD86/CD163 ratio, and elevated serum M1-related chemokines. A more inflammatory profile appeared to correlate with atherosclerotic risk, as in controls classical monocyte CD86/CD163 ratio was negatively correlated with HDL and apolipoprotein A1, and positively correlated with interleukin-1beta. CONCLUSIONS: We conclude that monocyte subsets show functional and phenotypic changes in cardiovascular disease and such changes are likely to contribute to atherosclerotic progression. PMID- 26871398 TI - On Inverse Association Between Helicobacter pylori Gastritis and Microscopic Colitis: The European Data. PMID- 26871399 TI - Branded name for ultramicronized palmitoylethanolamide and flawed science. PMID- 26871401 TI - What can we gain from increased placebo responses in U.S. clinical trials of neuropathic pain? PMID- 26871400 TI - Reply. PMID- 26871402 TI - New therapeutic options for respiratory tract infections. AB - PURPOSE OF REVIEW: The progressive increase of respiratory tract infections caused by multidrug-resistant organisms (MDROs) has been associated with delays in the prescription of an adequate antibiotic treatment and increased mortality, representing a major concern in both community and hospital settings. When infections because of methicillin-resistant Staphylococcus aureus (MRSA) are suspected, vancomycin still represents the first choice, although its efficacy has been recently questioned in favor of new drugs, reported to provide better clinical outcomes. Moreover, few therapeutic options are currently available for the treatment of severe infections caused by Multidrug-resistant (MDR) Gram negative pathogens, which are frequently resistant to all the available beta lactams, including carbapenems. We have reviewed the therapeutic options for the treatment of respiratory tract infections that have recently become available with promising implications for clinical practice, including ceftaroline, ceftrobiprole, tedizolid, telavancin, delafloxacin, eravacycline, and new beta lactams/beta-lactamase inhibitors. RECENT FINDINGS: A number of new antimicrobials with activity against MDROs have been recently approved for the treatment of respiratory tract infections, and other agents are under investigation. Recent developments, with a specific focus on the possible advantages of new drugs for the management of respiratory tract infections caused by MDROs in everyday clinical practice are discussed. SUMMARY: Newly approved and investigational drugs for the treatment of respiratory tract infections are expected to offer many advantages for the management of patients with suspected or confirmed infections caused by MDROs. Most promising features among new compounds include the broad spectrum of activity against both MRSA and MDR Gram negative bacteria, a limited risk of antimicrobial resistance, the availability of oral formulations, and a promising safety profile. PMID- 26871403 TI - Varicella zoster virus and giant cell arteritis. AB - PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a serious disease and the most common cause of vasculitis in the elderly. Here, studies describing the recent discovery of varicella zoster virus (VZV) in the temporal arteries of patients with GCA are reviewed. RECENT FINDINGS: GCA is characterized by severe headache/head pain and scalp tenderness. Many patients also have a history of vision loss, jaw claudication, polymyalgia rheumatica, fever, night sweats, weight loss, and fatigue. The erythrocyte sedimentation rate and C-reactive protein are usually elevated. Diagnosis is confirmed by temporal artery biopsy, which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. The present review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA but whose temporal artery biopsies are pathologically negative for GCA. Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, particularly in skip areas that correlate with adjacent GCA disease. SUMMARY: The presence of VZV in GCA-positive and GCA-negative temporal arteries reflects the possible role of VZV in triggering the immunopathology of GCA and indicates that both groups of patients should be treated with antivirals in addition to corticosteroids. Whether oral antiviral agents and steroids are as effective as intravenous acyclovir and steroids, and the dosage and duration of treatment, remain to be determined. PMID- 26871404 TI - Role of orexin-2 receptors in the nucleus accumbens in antinociception induced by carbachol stimulation of the lateral hypothalamus in formalin test. AB - Orexins, which are mainly produced by orexin-expressing neurons in the lateral hypothalamus (LH), play an important role in pain modulation. Previously, it has been established that the nucleus accumbens (NAc) is involved in the modulation of formalin-induced nociceptive responses, a model of tonic pain. In this study, the role of intra-accumbal orexin-2 receptors (OX2rs) in the mediation of formalin-induced pain was investigated. A volume of 0.5 MUl of 10, 20, and 40 nmol/l solutions of TCS OX2 29, an OX2r antagonist, were unilaterally microinjected into the NAc 5 min before an intra-LH carbachol microinjection (0.5 MUl of 250 nmol/l solution). After 5 min, animals received a subcutaneous injection of formalin 2.5% (50 MUl) into the hind paw. Pain-related behaviors were assessed at 5 min intervals during a 60-min test period. The findings showed that TCS OX2 29 administration dose dependently blocked carbachol-induced antinociception during both phases of formalin-induced pain. The antianalgesic effect of TCS OX2 29 was greater during the late phase compared with the early phase. These observations suggest that the NAc, as a part of a descending pain modulatory circuitry, partially mediates LH-induced analgesia in the formalin test through recruitment of OX2rs. This makes the orexinergic system a good potential therapeutic target in the control of persistent inflammatory pain. PMID- 26871406 TI - A dose-response study of separate and combined effects of the serotonin agonist 8 OH-DPAT and the dopamine agonist quinpirole on locomotor sensitization, cross sensitization, and conditioned activity. AB - Chronic treatment with the dopamine D2/D3 agonist, quinpirole, or the serotonin 1A agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), induces behavioral sensitization. It is not known whether both drugs produce sensitization through a shared mechanism. Here, we examine whether quinpirole and 8-OH-DPAT show cross-sensitization and impact sensitization, as would be expected from shared mechanisms. Male rats (N=208) were assigned randomly to 16 groups formed by crossing four doses of quinpirole (0, 0.03125, 0.0625, or 0.125 mg/kg) with four doses of 8-OH-DPAT (0, 0.03125, 0.625, or 0.125 mg/kg). After a course of 10 drug treatments administered twice per week in locomotor activity chambers, all groups were challenged on separate tests with quinpirole (0.1 mg/kg), 8-OH DPAT (0.1 mg/kg), or saline, and locomotor activity was evaluated. Challenge tests with quinpirole and 8-OHDPAT showed no cross-sensitization between the drugs. Chronic quinpirole (0.125 mg/kg) administration induced a sensitized quinpirole response that was attenuated dose-dependently by chronic 8-OH-DPAT cotreatment. Cotreatment with quinpirole (0.0625 mg/kg) and 8-OH-DPAT (all doses) induced quinpirole sensitization. Chronic 8-OH-DPAT (0.125 mg/kg) induced a sensitized 8-OHDPAT response that was prevented by chronic cotreatment with the lowest but not the highest dose of quinpirole. Cotreatment with 8-OHDPAT (0.0625) and quinpirole (0.125 mg/kg) induced sensitization to 8-OH-DPAT. The saline challenge test showed elevated locomotor activity in chronic quinpirole (0.125 mg/kg) and 8-OHDPAT (0.0625, 0.125 mg/kg) alone groups, and in seven of nine cotreated groups. The absence of cross-sensitization suggests separate mechanisms of sensitization to quinpirole and 8-OH-DPAT. Cotreatment effects suggest that induction of sensitization can be modulated by serotonin 1A and D2/D3 activity. PMID- 26871405 TI - Prior nicotine self-administration attenuates subsequent dopaminergic deficits of methamphetamine in rats: role of nicotinic acetylcholine receptors. AB - Preclinical studies have demonstrated that oral nicotine exposure attenuates long term dopaminergic damage induced by toxins, including repeated, high doses of methamphetamine. It is suggested that alterations in nicotinic acetylcholine receptor (nAChR) expression, including alpha4beta2* and alpha6beta2* subtypes, likely contribute to this protection. The current study extended these findings by investigating whether nicotine self-administration in male, Sprague-Dawley rats (a) attenuates short-term dopaminergic damage induced by methamphetamine and (b) causes alterations in levels of alpha4beta2* and alpha6beta2* nAChR subtypes. The findings indicate that nicotine self-administration (0.032 mg/kg/infusion for 14 days) per se did not alter alpha4beta2* and alpha6beta2* nAChR expression or dopamine transporter (DAT) expression and function. Interestingly, prior nicotine self-administration attenuated methamphetamine-induced decreases in DAT function when assessed 24 h, but not 1 h, after methamphetamine treatment (4*7.5 mg/kg/injection). The ability of nicotine to attenuate the effects of methamphetamine on DAT function corresponded with increases in alpha4beta2*, but not alpha6beta2*, nAChR binding density. Understanding the role of nAChRs in methamphetamine-induced damage has the potential to elucidate mechanisms underlying the etiology of disorders involving dopaminergic dysfunction, as well as to highlight potential new therapeutic strategies for prevention or reduction of dopaminergic neurodegeneration. PMID- 26871407 TI - Ultrasound Shear Wave Elastography for Liver Disease. A Critical Appraisal of the Many Actors on the Stage. AB - In the last 12 - 18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan((r)) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan((r)), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4 cm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely choosen depth within 8 cm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens((r)) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips((r)) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2 - 3 cm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1 - 2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba((r)), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer((r)) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i. e., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5 Hz and in larger regions; thus this technique is also termed real-time 2 D SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan((r)) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. . The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e. g. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2 - 3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. . Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. . Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan(r), where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. . Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED) PMID- 26871408 TI - EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III - Abdominal Treatment Procedures (Short Version). AB - The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online). PMID- 26871409 TI - EFSUMB statement on medical student education in ultrasound [short version]. AB - The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we summarise EFSUMB policy statements on medical student education in ultrasound. PMID- 26871410 TI - Letter to the Editor: Shear Wave Elastography May Be Superior to Grayscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology. PMID- 26871411 TI - Effects of molecule anchoring and dispersion on nanoscopic friction under electrochemical control. AB - The application of electric fields is a promising strategy for in situ control of friction. While there have recently been many experimental studies on friction under the influence of electric fields, theoretical understanding is very limited. Recently, we introduced a simple theoretical model for friction under electrochemical conditions that focused on the interaction of a force microscope tip with adsorbed molecules whose orientation was dependent on the applied electric field. Here we focus on the effects of anchoring of the molecules on friction. We show that anchoring affects the intensity and width of the peak in the friction that occurs near a reorientation transition of adsorbed molecules, and explain this by comparing the strength of molecule-molecule and molecule-tip interactions. We derive a dispersion relation for phonons in the layer of adsorbed molecules and demonstrate that it can be used to understand important features of the frictional response. PMID- 26871412 TI - Disorder-derived, strong tunneling attenuation in bis-phosphonate monolayers. AB - Monolayers of alkyl bisphosphonic acids (bisPAs) of various carbon chain lengths (C4, C8, C10, C12) were grown on aluminum oxide (AlO(x)) surfaces from solution. The structural and electrical properties of these self-assembled monolayers (SAMs) were compared with those of alkyl monophosphonic acids (monoPAs). Through contact angle (CA) and Kelvin-probe (KP) measurements, ellipsometry, and infrared (IR) and x-ray photoelectron (XPS) spectroscopies, it was found that bisPAs form monolayers that are relatively disordered compared to their monoPA analogs. Current-voltage (J-V) measurements made with a hanging Hg drop top contact show tunneling to be the prevailing transport mechanism. However, while the monoPAs have an observed decay constant within the typical range for dense monolayers, beta(mono) = 0.85 +/- 0.03 per carbon atom, a surprisingly high value, beta(bis) = 1.40 +/- 0.05 per carbon atom, was measured for the bisPAs. We attribute this to a strong contribution of 'through-space' tunneling, which derives from conformational disorder in the monolayer due to strong interactions of the distal phosphonic acid groups; they likely form a hydrogen-bonding network that largely determines the molecular layer structure. Since bisPA SAMs attenuate tunnel currents more effectively than do the corresponding monoPA SAMs, they may find future application as gate dielectric modification in organic thin film devices. PMID- 26871413 TI - Cross-linking multiwall carbon nanotubes using PFPA to build robust, flexible and highly aligned large-scale sheets and yarns. AB - Multi-walled carbon nanotube (CNT) structures, including unidirectionally aligned sheets and spun yarns, were fabricated by direct dry-spinning methods from spinnable CNT arrays. We improved the mechanical properties of the CNT structures. CNTs were tailored in sheets and yarns using perfluorophenyl azide (PFPA) as a binding agent. The azide group of PFPA bonds to graphene crystal surfaces under UV radiation exposed for 1 h. For the CNT sheet, Young's modulus increased from 1.6 to 32.9 GPa and tensile strength increased from 35.9 MPa to 144.5 MPa. For the CNT yarns Young's modulus increased from 29.5 to 78.0 GPa and tensile strength increased from 639.1 to 675.6 MPa. With this treatment, the CNT sheets became more robust and more flexible materials. Since cross-linking of CNTs by PFPA is a simple and rapid process, it is suitable for fabrication of enhanced CNT materials. PMID- 26871414 TI - Cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration-dependent manner in cancer cells. AB - BACKGROUND INFORMATION: Checkpoint adaptation (entry into mitosis with damaged DNA) is a process that links arrest at the G2/M cell cycle checkpoint and cell death in cancer cells. It is not known, however, whether cells treated with the genotoxic agent, cisplatin, undergo checkpoint adaptation or if checkpoint adaptation is a major pathway leading to cell death or not. Therefore, we investigated the relationship between treatment with cisplatin and cytotoxicity in cancer cells. RESULTS: Treatment of HT-29 human colorectal adenocarcinoma cells with cisplatin can induce cell death by one of two different mechanisms. Cells treated with a cytotoxic 30 MUM amount of cisplatin died after undergoing checkpoint adaptation. Before dying, however, almost all treated cells were positive for histone gammaH2AX staining and contained high levels of cyclin B1. Rounded cells appeared that were positive for phospho-Ser10 histone H3, with low levels of phospho-Tyr15 cyclin-dependent kinase 1, high levels of cyclin dependent kinase 1 activity, and checkpoint kinase 1 that was not phosphorylated on Ser345. These cells were in mitosis with damaged DNA. Strikingly, with 30 MUM cisplatin, 81% of cells had entered mitosis before dying. By contrast, after treatment with 100 MUM cisplatin, nearly all cells died but only 7% of cells had entered mitosis. Instead, these cells died by apoptosis; they were positive for annexin-V staining, contained cleaved caspase 3, cleaved caspase 9 and cleaved PARP and did not contain Mcl-1. CONCLUSIONS: Our data demonstrate that cancer cells treated with cisplatin can undergo one of two modes of cell death depending upon concentration used. These findings suggest that checkpoint adaptation is likely a primary pathway in genotoxic cell death at pharmacological concentrations of cisplatin. SIGNIFICANCE: Checkpoint adaptation might be a common biochemical pathway taken by human cancer cells in response to pharmacologically relevant, cytotoxic amounts of damaged DNA. PMID- 26871415 TI - Enzymatic generation of peptides from potato proteins by selected proteases and characterization of their structural properties. AB - The use of low grade starting material for the generation of peptides with bioactivity properties is of interest. The proteins from the potato starch industry byproduct is a promising source, as several health benefits may be associated with their hydrolysates. The efficiency of selected proteases (Novo Pro-D, Alcalase, Flavourzyme, and Papain), exhibiting different substrate specificities and cleavage action modes, to hydrolyze potato protein isolate (patatin and protease inhibitors) was investigated. Novo Pro-D resulted in the lowest degree of hydrolysis, whereas Alcalase, Flavourzyme, and Papain exhibited a high catalytic efficiency for the hydrolysis of potato proteins. The degree of hydrolysis behaved in a concentration dependent manner. However, the end-product profile (peptides and free amino acids) was dependent not only on the protease specificity, its cleavage action mode (endo/exo) and the availability of the intermediate substrates but also on the contribution of the protease inhibitors to the reaction kinetics through their inhibitory effects. Indeed, the dependence of the exo-activity on the catalytic efficiency of the endo-action of protease was shown to be significant. Papain generated more unique peptide sequences with homology assessment matching several potato proteins when compared with Flavourzyme. This can be attributed to the high exo-peptidase activity of Flavourzyme resulting in the generation of shorter peptides which were difficult to match. Flavourzyme produced more peptides originated from patatin fraction, whereas Papain resulted in the release of more peptides corresponding to the protease inhibitor fractions. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:420-429, 2016. PMID- 26871416 TI - Intranasal administration of midazolam in blue-and-yellow macaws (Ara araruana): evaluation of sedative effects. PMID- 26871417 TI - Treatment of Moderate to Severe Pediatric Psoriasis: A Retrospective Case Series. AB - BACKGROUND: Psoriasis has an estimated prevalence of 0.5% to 2.0% in children. There is a paucity of data regarding the management and safety of treatments currently available for children with moderate to severe psoriasis. The aim of this study was to evaluate the treatment response and safety of systemic therapies used to manage moderate to severe pediatric psoriasis in a single referral center. Despite a small sample size, it was hypothesized that multiple therapeutics used for adult psoriasis would have a similar side-effect profile and positive disease response when used in a pediatric population. METHODS: A retrospective case series evaluated 51 children with moderate to severe psoriasis treated with systemic therapies for adverse event occurrence and for disease response using a 5-point Physician Global Assessment scale. RESULTS: Fifty-one patients, some of whom used multiple treatment options, produced 80 treatment data points. Adverse events were reported in 29 of these 80 treatments, with most being minor, subjective side effects. Overall, the most commonly reported side effect was fatigue, which was reported in 7.5% of treatments. Because of the small sample size, the data collected are limited and may not represent a comprehensive safety profile, nor do they allow comparison of efficacy between therapies. This case series found that biologic and immunomodulating therapies provide well-tolerated treatments with positive disease response for moderate to severe pediatric psoriasis. CONCLUSION: Although sample size and study design limit the data from this study, the study provides some guidance where little exists and helps to support the use of these treatments in this setting. PMID- 26871419 TI - Exploring the process of professional socialisation and development during pharmacy pre-registration training in England. AB - OBJECTIVES: To explore the process of professional socialisation in pharmacy trainees during pre-registration training. METHODS: A prospective, longitudinal qualitative design was used. A purposive sample of 20 trainees from community and hospital pharmacy in North West England was recruited. A total of 79 semi structured interviews were conducted with trainees on three occasions during training and once four months after training. Data were analysed thematically using template analysis. KEY FINDINGS: Early on in training, non-pharmacists played a significant role in socialising trainees into the work setting; pharmacists played the stronger role towards the end. Pre-registration tutors were strong role models throughout training. Training experiences differed between settings, where services provided and patient mix varied. Hospital trainees learnt about specialist medicines on ward rotations. Community trainees developed knowledge of over-the-counter, and less complex, medicines. In hospital, trainees were exposed to a range of role models in comparison to community where this was generally limited to a small pharmacy team. Newly qualified pharmacists were challenged by having full responsibility and accountability. CONCLUSION: This study showed the experiences encountered by trainees that affect their professional socialisation. More standardisation across training sites may reduce the variation in experiences and professional socialisation and development. Formal training for pre-registration tutors and support staff that play a key role in supporting trainees could be considered. Support for newly qualified pharmacists may allay the challenging transition they face when entering practice. PMID- 26871418 TI - Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to cell spread. AB - Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes, mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral-virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA-binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant - which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell-to-cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter - suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non-antibiotic therapeutics for gram positive infections. (c) 2016 John Wiley & Sons Ltd. PMID- 26871421 TI - Influence of gamma-Secretase Inhibitor 24-Diamino-5-Phenylthiazole DAPT on Platelet Activation. AB - BACKGROUND/AIMS: DAPT (24-diamino-5-phenylthiazole) inhibits gamma-secretase, which cleaves the signaling molecule CD44, a negative regulator of platelet activation and apoptosis. CD44 is a co-receptor for macrophage migration inhibitory factor (MIF) an anti-apoptotic pro-inflammatory cytokine expressed and released from blood platelets. Whether DAPT influences platelet function, remained, however, elusive. Activators of platelets include collagen related peptide (CRP). The present study thus explored whether DAPT modifies the stimulating effect of CRP on platelet function. METHODS: Platelets isolated from wild-type mice were exposed for 30 minutes to DAPT (10 uM). Flow cytometry was employed to estimate Orai1 abundance with specific antibodies, cytosolic Ca(2+) activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P selectin abundance, integrin activation from alpha(IIb)beta3 integrin abundance, generation of reactive oxygen species (ROS) from DCFDA fluorescence, mitochondrial transmembrane potential from TMRE fluorescence, phospholipid scrambling of the cell membrane from annexin-V-binding, relative platelet volume from forward scatter and aggregation utilizing staining with CD9-APC and CD9-PE. RESULTS: Exposure of platelets to 2-5 ug/ml CRP was followed by significant increase of Orai1 abundance, [Ca2+]i, and P-selectin abundance, as well as by alpha(IIb)beta3 integrin activation, ROS generation, mitochondrial depolarization, enhanced annexin-V-binding, decreased cell volume, and aggregation. All CRP induced effects were significantly blunted in the presence of DAPT. CONCLUSIONS: The gamma-secretase inhibitor DAPT counteracts agonist induced platelet activation, apoptosis and aggregation. PMID- 26871420 TI - Assessment of the precision and reproducibility of ventricular volume, function, and mass measurements with ferumoxytol-enhanced 4D flow MRI. AB - PURPOSE: To compare the precision and interobserver agreement of ventricular volume, function, and mass quantification by 3D time-resolved (4D) flow MRI relative to cine steady-state free precession (SSFP). MATERIALS AND METHODS: With Institutional Research Board approval, informed consent, and HIPAA compliance, 22 consecutive patients with congenital heart disease (CHD) (10 males, 6.4 +/- 4.8 years) referred for 3T ferumoxytol-enhanced cardiac MRI were prospectively recruited. Complete ventricular coverage with standard 2D short-axis cine SSFP and whole chest coverage with axial 4D flow were obtained. Two blinded radiologists independently segmented images for left ventricular (LV) and right ventricular (RV) myocardium at end systole (ES) and end diastole (ED). Statistical analysis included linear regression, analysis of variance (ANOVA), Bland-Altman (BA) analysis, and intraclass correlation (ICC). RESULTS: Significant positive correlations were found between 4D flow and SSFP for ventricular volumes (r = 0.808-0.972, P < 0.001), ejection fraction (EF) (r = 0.900-928, P < 0.001), and mass (r = 0.884-0.934, P < 0.001). BA relative limits of agreement for both ventricles were between -52% to 34% for volumes, -29% to 27% for EF, and -41% to 48% for mass, with wider limits of agreement for the RV compared to the LV. There was no significant difference between techniques with respect to mean square difference of ED-ES mass for either LV (F = 2.05, P = 0.159) or RV (F = 0.625, P = 0.434). Interobserver agreement was moderate to good with both 4D flow (ICC 0.523-0.993) and SSFP (ICC 0.619-0.982), with overlapping confidence intervals. CONCLUSION: Quantification of ventricular volume, function, and mass can be accomplished with 4D flow MRI with precision and interobserver agreement comparable to that of cine SSFP. J. Magn. Reson. Imaging 2016;44:383 392. PMID- 26871422 TI - Three Cases of Intravascular Large B-Cell Lymphoma Detected in a Biopsy of Skin Lesions. AB - Intravascular large B-cell lymphoma (IVL) is a rare subtype of extranodal malignant lymphoma. The proliferation of neoplastic B cells within small blood vessels causes eruptions and other symptoms in a variety of organs. The random skin biopsy is useful for diagnosing this condition in its early stages. In order to assess the diagnostic utility of this method, we examined 3 cases with the aim of comparing the occurrence of tumor cells in lesional and healthy-looking skin by performing a random skin biopsy of 32 separate sites. Our findings from the total of 32 biopsy specimens collected from the 3 cases indicated that 16 of the 17 sites on the lesional skin and 1 of the 15 sites on the healthy-looking skin were positive for neoplastic cells. This finding suggested that IVL cells occurred more frequently in the lesional skin than in the healthy-looking skin. PMID- 26871423 TI - Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms. AB - OBJECTIVES: Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. METHODS: A series of 583 consecutive cancer patients (68.4 +/- 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. RESULTS: Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. CONCLUSIONS: The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients. PMID- 26871424 TI - Morphometric Analysis of Predictors of Cervical Syrinx Formation in the Setting of Chiari I Malformation. AB - BACKGROUND/AIMS: We performed a morphometric analysis of Chiari I malformations to look for predictors of cervical syrinx formation. METHODS: Eighteen patients with Chiari I malformation and associated cervical syrinx and 16 patients with Chiari I malformation without associated cervical syrinx were included in the study. Chiari I size was obtained from the radiology report; foramen magnum diameter, cerebellar volume, posterior fossa volume and intracranial volume were calculated using OsiriX software, and average measurements were compared between the two groups. RESULTS AND CONCLUSION: Patients with Chiari I with syrinx had an average tonsillar descent of 13.03 +/- 5.31 mm compared to 9.25 +/- 3.31 mm in the Chiari I without syrinx group (p < 0.05). Patients with Chiari I and syrinx also showed increased cerebellar crowding with a higher cerebellar volume to posterior fossa volume ratio; however, this difference was not significant (0.83 vs. 0.81; p = 0.1872). No difference between groups was found in posterior fossa volume, intracranial volume and foramen magnum diameter. Therefore, only Chiari I size based on the extent of tonsillar herniation was found to be a determinant of cervical syrinx formation. PMID- 26871425 TI - Treatment of suicidal depression with ketamine in rapid cycling bipolar disorder. PMID- 26871426 TI - Acute polymorphic psychotic disorder: Differences from other acute and transient psychoses. PMID- 26871427 TI - Comparison of attitudes of the psychiatrists and nurses towards patients with mental illness in a Chinese psychiatric hospital: Implications for training. PMID- 26871428 TI - Selective and Stable Ethylbenzene Dehydrogenation to Styrene over Nanodiamonds under Oxygen-lean Conditions. AB - For the first time, significant improvement of the catalytic performance of nanodiamonds was achieved for the dehydrogenation of ethylbenzene to styrene under oxygen-lean conditions. We demonstrated that the combination of direct dehydrogenation and oxidative dehydrogenation indeed occurred on the nanodiamond surface throughout the reaction system. It was found that the active sp(2)-sp(3) hybridized nanostructure was well maintained after the long-term test and the active ketonic carbonyl groups could be generated in situ. A high reactivity with 40% ethylbenzene conversion and 92% styrene selectivity was obtained over the nanodiamond catalyst under oxygen-lean conditions even after a 240 h test, demonstrating the potential of this procedure for application as a promising industrial process for the ethylbenzene dehydrogenation to styrene without steam protection. PMID- 26871429 TI - DNA, the central molecule of aging. AB - Understanding the molecular mechanism of aging could have enormous medical implications. Despite a century of research, however, there is no universally accepted theory regarding the molecular basis of aging. On the other hand, there is plentiful evidence suggesting that DNA constitutes the central molecule in this process. Here, we review the roles of chromatin structure, DNA damage, and shortening of telomeres in aging and propose a hypothesis for how their interplay leads to aging phenotypes. PMID- 26871430 TI - Genetic variants in multisynthetase complex genes are associated with DNA damage levels in Chinese populations. AB - Aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) form a multisynthetase complex (MSC) and play an important role in the process of DNA damage repair. We hypothesized that genetic variants in key ARSs and AIMPs might regulate the DNA damage response. Therefore, we systematically screened 23 potentially functional polymorphisms in MSC genes and evaluated the association between the genetic variants and DNA damage levels in 307 subjects from three cities in southern, central and northern China (Zhuhai, Wuhan and Tianjin, respectively). We examined personal 24-h PM2.5 exposure levels and DNA damage levels in peripheral blood lymphocytes for each subject. We found that the variant allele of rs12199241 in AIMP3 was significantly associated with DNA damage levels (beta=0.343, 95%CI: 0.133-0.554, P=0.001). Meanwhile, the results of rs5030754 in EPRS and rs3784929 in KARS indicated their suggestive roles in DNA damage processes (beta=0.331, 95%CI: 0.062-0.599, P=0.016 for rs5030754; beta=0.192, 95%CI: 0.016-0.368, P=0.033 for rs3784929, respectively). After multiple testing, rs12199241 was still significantly associated with DNA damage levels. Combined analysis of these three polymorphisms showed a significant allele-dosage association between the number of risk alleles and higher DNA damage levels (Ptrend<0.001). These findings indicate that genetic variants in MSC genes may account for PM2.5-modulated DNA damage levels in Chinese populations. PMID- 26871432 TI - Comparison of the Diagnostic Accuracy of Three Rapid Tests for the Serodiagnosis of Hepatic Cystic Echinococcosis in Humans. AB - BACKGROUND: The diagnosis of cystic echinococcosis (CE) is based primarily on imaging, in particular with ultrasound for abdominal CE, complemented by serology when imaging results are unclear. In rural endemic areas, where expertise in ultrasound may be scant and conventional serology techniques are unavailable due to lack of laboratory equipment, Rapid Diagnostic Tests (RDTs) are appealing. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the diagnostic accuracy of 3 commercial RDTs for the diagnosis of hepatic CE. Sera from 59 patients with single hepatic CE cysts in well-defined ultrasound stages (gold standard) and 25 patients with non-parasitic cysts were analyzed by RDTs VIRapid HYDATIDOSIS (Vircell, Spain), Echinococcus DIGFA (Unibiotest, China), ADAMU-CE (ICST, Japan), and by RIDASCREEN Echinococcus IgG ELISA (R-Biopharm, Germany). Sensitivity, specificity and ROC curves were compared with McNemar and t-test. For VIRapid and DIGFA, correlation between semiquantitative results and ELISA OD values were evaluated by Spearman's coefficient. Reproducibility was assessed on 16 randomly selected sera with Cohen's Kappa coefficient. Sensitivity and Specificity of VIRapid (74%, 96%) and ADAMU-CE (57%, 100%) did not differ from ELISA (69%, 96%) while DIGFA (72%, 72%) did (p = 0.045). ADAMU-CE was significantly less sensitive in the diagnosis of active cysts (p = 0.019) while DIGFA was significantly less specific (p = 0.014) compared to ELISA. All tests were poorly sensitive in diagnosing inactive cysts (33.3% ELISA and ADAMU-CE, 42.8% DIGFA, 47.6% VIRapid). The reproducibility of all RDTs was good-very good. Band intensity of VIRapid and DIGFA correlated with ELISA OD values (r = 0.76 and r = 0.79 respectively, p<0.001). CONCLUSIONS/SIGNIFICANCE: RDTs may be useful in resource-poor settings to complement ultrasound diagnosis of CE in uncertain cases. VIRapid test appears to perform best among the examined kits, but all tests are poorly sensitive in the presence of inactive cysts, which may pose problems with accurate diagnosis. PMID- 26871431 TI - Expression of Ferritin Light Chain (FTL) Is Elevated in Glioblastoma, and FTL Silencing Inhibits Glioblastoma Cell Proliferation via the GADD45/JNK Pathway. AB - Accumulating evidence suggests that iron-associated proteins contribute to tumor initiation and development. Ferritin light chain (FTL), a key protein in iron metabolism, is associated with the survival of glioblastoma multiforme (GBM) patients; however, the molecular mechanisms underlying this association remain largely unclear. Therefore, in the present study, we investigated the role of FTL in the pathogenesis of GBM. By using quantitative real-time RT-PCR, we found that expression of FTL was higher in patients with GBM than in those with low-grade glioma. Immunofluorescence showed that FTL was mainly localized in the nucleus of GBM cells and was closely associated with mitotic spindles. Knockdown of FTL resulted in inhibition of cell growth and activation of the GADD45A/JNK pathway in GBM cells. Immunoblotting revealed that levels of GADD45A protein decreased in GBM cells when FTL expression increased. Furthermore, transfection of GADD45A in GBM cells significantly decreased cell viability, and this effect was impeded by co-transfection of FTL. Moreover, FTL was found to localize with GADD45A in GBM cells, and a coimmunoprecipitation experiment showed that the two proteins physically interacted. Taken together, these results demonstrate a novel mechanism by which FTL regulates the growth of GBM cells via the GADD45/JNK pathway. PMID- 26871435 TI - Experimental Study of the Bending Properties and Deformation Analysis of Web Reinforced Composite Sandwich Floor Slabs with Four Simply Supported Edges. AB - Web-reinforced composite sandwich panels exhibit good mechanical properties in one-way bending, but few studies have investigated their flexural behavior and deformation calculation methods under conditions of four simply supported edges. This paper studies the bending performance of and deformation calculation methods for two-way web-reinforced composite sandwich panels with different web spacing and heights. Polyurethane foam, two-way orthogonal glass-fiber woven cloth and unsaturated resin were used as raw materials in this study. Vacuum infusion molding was used to prepare an ordinary composite sandwich panel and 5 web reinforced composite sandwich panels with different spacing and web heights. The panels were subjected to two-way panel bending tests with simple support for all four edges. The mechanical properties of these sandwich panels during the elastic stage were determined by applying uniformly distributed loads. The non-linear mechanical characteristics and failure modes were obtained under centrally concentrated loading. Finally, simulations of the sandwich panels, which used the mechanical model established herein, were used to deduce the formulae for the deflection deformation for this type of sandwich panel. The experimental results show that webs can significantly improve the limit bearing capacity and flexural rigidity of sandwich panels, with smaller web spacing producing a stronger effect. When the web spacing is 75 mm, the limit bearing capacity is 4.63 times that of an ordinary sandwich panel. The deduced deflection calculation formulae provide values that agree well with the measurements (maximum error <15%). The results that are obtained herein can provide a foundation for the structural design of this type of panel. PMID- 26871434 TI - Maternal Snoring May Predict Adverse Pregnancy Outcomes: A Cohort Study in China. AB - OBJECTIVE: To examine the prevalence of snoring during pregnancy and its effects on key pregnancy outcomes. METHODS: Pregnant women were consecutively recruited in their first trimester. Habitual snoring was screened by using a questionnaire in the 1st and 3rd trimester, respectively. According to the time of snoring, participants were divided into pregnancy onset snorers, chronic snorers and non snorers. Logistic regressions were performed to examine the associations between snoring and pregnancy outcomes. RESULTS: Of 3 079 pregnant women, 16.6% were habitual snorers, with 11.7% were pregnancy onset snorers and 4.9% were chronic snorers. After adjusting for potential confounders, chronic snorers were independently associated with gestational diabetes mellitus (GDM) (RR 1.66, 95%CI 1.09-2.53). Both pregnancy onset and chronic snorers were independently associated with placental adhesion (RR 1.96, 95%CI 1.17-3.27, and RR 2.33, 95%CI 1.22-4.46, respectively). Pregnancy onset snorers were at higher risk of caesarean delivery (RR 1.37, 95%CI 1.09-1.73) and having macrosomia (RR 1.54, 95%CI 1.05-2.27) and large for gestational age (LGA) (RR 1.71, 95%CI 1.31-2.24) infants. In addition, being overweight or obese before pregnancy plays an important role in mediating snoring and adverse pregnancy outcomes. CONCLUSIONS: Maternal snoring may increase the risk of adverse pregnancy outcomes, and being overweight or obese before pregnancy with snoring is remarkable for researchers. Further studies are still needed to confirm our results. PMID- 26871436 TI - The Synthesis of a Coumarin Carbohydrazide Dinuclear Copper Complex Based Fluorescence Probe and Its Detection of Thiols. AB - Small-molecule thiols, such as cysteine (CYS) and glutathione (GSH), are essential for maintaining the cellular redox environment and play important roles in regulating various cellular physiological functions. A fluorescence probe (compound 1-Cu2+) for thiols based on coumarin carbohydrazide dinuclear copper complex was developed. Compound 1 was synthesized from the reaction of 7 (diethylamino)-2-oxo-2H-chromene-3-carbohydrazide with 4-tert-butyl-2,6- diformylphenol. Accordingly, the copper complex (compound 1-Cu2+) was prepared by mixing compound 1 with 2 equivalents copper ions. Compound 1 had strong fluorescence while compound 1-Cu2+ hardly possessed fluorescence owing to the quenching nature of paramagnetism Cu2+ to the fluorescence molecule excited state. However, the fluorescence intensity of compound 1-Cu2+ was increased dramatically after the addition of thiol-containing amino acids, but not the other non-sulfhydryl amino acids. UV-vis absorption and fluorescence spectra indicated that compound 1-Cu2+ had good selectivity and sensitivity for thiols such as glutathione in CH3CN:H2O (3:2, v/v) PBS solution. The fluorescence imaging experiments implied that compound 1-Cu2+ has potential application in thiol-containing amino acids detection in living cells. PMID- 26871437 TI - Progression of Neuronal Damage in an In Vitro Model of the Ischemic Penumbra. AB - Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2~20mmHg) reduced spontaneous activity, due to impeded synaptic function. After ~6 hours, activity and connectivity partially recovered, even during continuing hypoxia. If the oxygen supply was restored within 12 hours, changes in network connectivity were completely reversible. For longer periods of hypoxia (12-30 h), activity levels initially increased, but eventually decreased and connectivity changes became partially irreversible. After ~30 hours, all functional connections disappeared and no activity remained. Since this complete silence seemed unrelated to hypoxic depths, but always followed an extended period of low activity, we speculate that irreversible damage (at least partly) results from insufficient neuronal activation. This opens avenues for therapies to improve recovery by neuronal activation. PMID- 26871439 TI - Omnivory of an Insular Lizard: Sources of Variation in the Diet of Podarcis lilfordi (Squamata, Lacertidae). AB - Through 17 years and from a sample of 7,790 faecal pellets and 26,346 prey items, we studied the diet of the Balearic lizard Podarcis lilfordi in Aire Island (Menorca, Balearic Islands, Spain). We analysed the diet in terms of prey frequencies, as well as by their volume and biomass contributions. The diet of the Balearic lizard was extremely variable through the years, months and areas under study. The dominance of small clumped prey, particularly ants, was confirmed. However, the main contribution by volume corresponded to beetles, with a relevant role for Diplopoda and terrestrial Isopoda during some months and at particular areas of the island. Several prey items were probably captured at the base of shrubs, under stones or inside rock crevices. Therefore, our estimations of electivity would only be reliable for epigeal and flying prey. The capacity of the Balearic lizard to include marine subsidies in its diet, such as coastal crustaceans, is noteworthy. Also, its consumption of carrion from carcasses of gulls and rabbits and leftovers from human visitors is remarkable. Juvenile conspecifics can also be a sporadic food resource, especially during the second half of summer, whereas the consumption of vegetal matter is constant for each whole year. The shifts of vegetal exploitation among areas of the island and months take place according to availability of different plant species at each area or during a given period. Thus, lizards are able to conduct a thorough monitoring of plant phenology, exploiting a large variety of plant species. Omnivory does not imply the indiscriminate inclusion of any edible food in its diet. Rather, the inclusion of several food items means the adoption of a wide range of foraging behaviours adapted to the exploitation of each food resource. PMID- 26871438 TI - MW151 Inhibited IL-1beta Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses. AB - A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a closed head injury model of mild TBI suppressed acute cytokine up-regulation and downstream cognitive impairment. Here, we report results from a diffuse brain injury model in mice using midline fluid percussion. Low dose (0.5-5.0 mg/kg) administration of MW151 suppresses interleukin-1 beta (IL-1beta) levels in the cortex while sparing reactive microglia and astrocyte responses. To probe molecular mechanisms, we used live cell imaging of the BV-2 microglia cell line to demonstrate that MW151 does not affect proliferation, migration, or phagocytosis of the cells. Our results provide insight into the roles of glial responses to brain injury and indicate the feasibility of using appropriate dosing for selective therapeutic modulation of injurious IL-1beta increases while sparing other glial responses to injury. PMID- 26871440 TI - Networking in the Plant Microbiome. AB - Almost all higher organisms, including plants, insects, and mammals, are colonized by complex microbial communities and harbor a microbiome. Emerging studies with plants reveal that these microbiomes are structured and form complex, interconnected microbial networks. Within these networks, different taxa have different roles, and keystone species have been identified that could be crucial for plant health and ecosystem functioning. A new paper in this issue of PLOS Biology by Agler et al. highlights the presence of microbial hubs in these networks that may act as mediators between the plant and its microbiome. A next major frontier is now to link microbiome composition to function. In order to do this, we present a number of hypothetical examples of how microbiome diversity and function potentially influence host performance. PMID- 26871441 TI - Identification of Cell Cycle Dependent Interaction Partners of the Septins by Quantitative Mass Spectrometry. AB - The septins are a conserved family of GTP-binding proteins that, in the baker's yeast, assemble into a highly ordered array of filaments at the mother bud neck. These filaments undergo significant structural rearrangements during the cell cycle. We aimed at identifying key components that are involved in or regulate the transitions of the septins. By combining cell synchronization and quantitative affinity-purification mass-spectrometry, we performed a screen for specific interaction partners of the septins at three distinct stages of the cell cycle. A total of 83 interaction partners of the septins were assigned. Surprisingly, we detected DNA-interacting/nuclear proteins and proteins involved in ribosome biogenesis and protein synthesis predominantly present in alpha factor arrested that do not display an assembled septin structure. Furthermore, two distinct sets of regulatory proteins that are specific for cells at S-phase with a stable septin collar or at mitosis with split septin rings were identified. Complementary methods like SPLIFF and immunoprecipitation allowed us to more exactly define the spatial and temporal characteristics of selected hits of the AP-MS screen. PMID- 26871442 TI - Hepatitis C Virus Resistance to Carbohydrate-Binding Agents. AB - Carbohydrate binding agents (CBAs), including natural lectins, are more and more considered as broad-spectrum antivirals. These molecules are able to directly inhibit many viruses such as Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Dengue Virus, Ebola Virus or Severe Acute Respiratory Syndrome Coronavirus through binding to envelope protein N-glycans. In the case of HIV, it has been shown that CBAs select for mutant viruses with N-glycosylation site deletions which are more sensitive to neutralizing antibodies. In this study we aimed at evaluating the HCV resistance to CBAs in vitro. HCV was cultivated in the presence of increasing Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A or Griffithsin concentrations, during more than eight weeks. At the end of lectin exposure, the genome of the isolated strains was sequenced and several potential resistance mutations in the E1E2 envelope glycoproteins were identified. The effect of these mutations on viral fitness as well as on sensitivity to inhibition by lectins, soluble CD81 or the 3/11 neutralizing antibody was assessed. Surprisingly, none of these mutations, alone or in combination, conferred resistance to CBAs. In contrast, we observed that some mutants were more sensitive to 3/11 or CD81-LEL inhibition. Additionally, several mutations were identified in the Core and the non-structural proteins. Thus, our results suggest that in contrast to HIV, HCV resistance to CBAs is not directly conferred by mutations in the envelope protein genes but could occur through an indirect mechanism involving mutations in other viral proteins. Further investigations are needed to completely elucidate the underlying mechanisms. PMID- 26871444 TI - Correction: Classifiers for Ischemic Stroke Lesion Segmentation: A Comparison Study. PMID- 26871445 TI - Correction: Spatial Variation of Phosphorous Retention Capacity in Subsurface Flow Constructed Wetlands: Effect of Wetland Type and Inflow Loading. PMID- 26871443 TI - Inverse Association of Plasma IgG Antibody to Aggregatibacter actinomycetemcomitans and High C-Reactive Protein Levels in Patients with Metabolic Syndrome and Periodontitis. AB - The association between clinically diagnosed periodontitis, a common chronic oral infection, and metabolic syndrome has been previously reported. The aim of this study was to investigate the association of plasma IgG levels against Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, C-reactive protein, and periodontal status with metabolic syndrome. Plasma IgG levels and C-reactive protein were measured by enzyme-linked immunosorbent assay, and salivary levels of A. actinomycetemcomitans and P. gingivalis were determined by quantitative real-time polymerase chain reaction. Among 127 individuals aged 35-76 years, 57 participants had metabolic syndrome and severe periodontitis, 25 had metabolic syndrome and an absence of severe periodontitis, 17 healthy individuals had severe periodontitis, and 28 healthy individuals were without severe periodontitis. Patients with metabolic syndrome had reduced humoral immune response to A. actinomycetemcomitans (p = 0.008), regardless of their salivary levels or periodontitis status compared with healthy participants. The IgG antibody response to P. gingivalis, regardless of their salivary levels or participants' health condition, was significantly higher in severe periodontitis patients (p<0.001). Plasma IgG titers for P. intermedia were inconsistent among metabolic syndrome or periodontal participants. Our results indicate that the presence of lower levels of IgG antibodies to A. actinomycetemcomitans (OR = 0.1; 95%CI 0.0-0.7), but not P. gingivalis, a severe periodontitis status (OR = 7.8; 95%CI 1.1-57.0), high C-reactive protein levels (OR = 9.4; 95%CI 1.0-88.2) and body mass index (OR = 3.0; 95%CI 1.7-5.2), are associated with the presence of metabolic syndrome. The role of the decreased IgG antibody response to A. actinomycetemcomitans, increased C-reactive protein levels on the association between periodontal disease and metabolic syndrome in a group of Thai patients is suggested. PMID- 26871446 TI - Spaceborne SAR Imaging Algorithm for Coherence Optimized. AB - This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR) by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR) research and application. PMID- 26871447 TI - Large-Scale Modelling of the Environmentally-Driven Population Dynamics of Temperate Aedes albopictus (Skuse). AB - The Asian tiger mosquito, Aedes albopictus, is a highly invasive vector species. It is a proven vector of dengue and chikungunya viruses, with the potential to host a further 24 arboviruses. It has recently expanded its geographical range, threatening many countries in the Middle East, Mediterranean, Europe and North America. Here, we investigate the theoretical limitations of its range expansion by developing an environmentally-driven mathematical model of its population dynamics. We focus on the temperate strain of Ae. albopictus and compile a comprehensive literature-based database of physiological parameters. As a novel approach, we link its population dynamics to globally-available environmental datasets by performing inference on all parameters. We adopt a Bayesian approach using experimental data as prior knowledge and the surveillance dataset of Emilia Romagna, Italy, as evidence. The model accounts for temperature, precipitation, human population density and photoperiod as the main environmental drivers, and, in addition, incorporates the mechanism of diapause and a simple breeding site model. The model demonstrates high predictive skill over the reference region and beyond, confirming most of the current reports of vector presence in Europe. One of the main hypotheses derived from the model is the survival of Ae. albopictus populations through harsh winter conditions. The model, constrained by the environmental datasets, requires that either diapausing eggs or adult vectors have increased cold resistance. The model also suggests that temperature and photoperiod control diapause initiation and termination differentially. We demonstrate that it is possible to account for unobserved properties and constraints, such as differences between laboratory and field conditions, to derive reliable inferences on the environmental dependence of Ae. albopictus populations. PMID- 26871448 TI - A Randomized Controlled Trial of Innovative Postpartum Care Model for Mother-Baby Dyads. AB - OBJECTIVE: To evaluate the efficacy, safety, and maternal satisfaction of a newly established integrative postpartum community-based clinic providing comprehensive support for mothers during the first month after discharge from the hospital. Our primary interests were breastfeeding rates, readmission and patient satisfaction. METHODS: A randomized controlled trial was conducted in Ottawa, Canada, where 472 mothers were randomized via a 1:2 ratio to either receive standard of care (n = 157) or to attend the postpartum breastfeeding clinic (n = 315). Outcome data were captured through questionnaires completed by the participants at 2, 4, 12 and 24 weeks postpartum. Unadjusted and adjusted logistic regression models were conducted to determine the effect of the intervention on exclusive breastfeeding at 12 weeks (primary outcome). Secondary outcomes included breastfeeding rate at 2, 4 and 24 weeks, breastfeeding self-efficacy scale, readmission rate, and satisfaction score. RESULTS: More mothers in the intervention group (n = 195, 66.1%) were exclusively breastfeeding at 12 weeks compared to mothers in the control group (n = 81, 60.5%), however no statistically significant difference was observed (OR = 1.28; 95% CI:0.84-1.95)). The rate of emergency room visits at 2 weeks for the intervention group was 11.4% compared to the standard of care group (15.2%) (OR = 0.69; 95% CI: 0.39-1.23). The intervention group was significantly more satisfied with the overall care they received for breastfeeding compared to the control group (OR = 1.96; 95% CI: 3.50-6.88)). CONCLUSION: This new model of care did not significantly increase exclusive breastfeeding at 12 weeks. However, there were clinically meaningful improvements in the rate of postnatal problems and satisfaction that support this new service delivery model for postpartum care. A community-based multidisciplinary postpartum clinic is feasible to implement and can provide appropriate and highly satisfactory care to mother-baby dyads. This model of care may be more beneficial in a population that is not already predisposed to breastfeed. TRIAL REGISTRATION: ClinicalTrials.gov NCT02043119. PMID- 26871449 TI - Pretreatment Gastric Lavage Reduces Postoperative Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasms. AB - AIM: For patients receiving endoscopic submucosal dissection (ESD), there is urgent need pertaining to the prevention of postoperative bleeding. We conducted a retrospective propensity score-matched study that evaluated whether pre-ESD gastric lavage prevents postoperative bleeding after ESD for gastric neoplasms. METHODS: From September 2002 to October 2015, the 760 consecutive patients receiving ESD for gastric neoplasm were enrolled and data regarding them were retrospectively analyzed. All patients received conventional preventive treatment against delayed bleeding after ESD, including the administration of proton pump inhibitor and preventive coagulation of visible vessels, at the end of the ESD procedure. RESULTS: Pre-ESD risk factors for postoperative bleeding included tumor size and no gastric lavage. Using multivariate analysis tumor size >2.0 cm (HR 2.90, 95% CI 1.65-5.10, p = 0.0002) and no gastric lavage (HR 3.20, 95% CI 1.13-9.11, p = 0.029) were found to be independent risk factors. Next, we evaluated the effect of gastric lavage on the prevention of post-ESD bleeding using a propensity score-matching method. A total of 284 subjects (142 per group) were selected. Adjusted odds ratio of gastric lavage for post-ESD bleeding was 0.25 (95% CI 0.071-0.886, p = 0.032). CONCLUSION: Pretreatment gastric lavage reduced postoperative bleeding in patients receiving ESD for gastric neoplasm. PMID- 26871450 TI - My Early Days with Ari Helenius: Detergents and Viruses. PMID- 26871451 TI - Nest Material Shapes Eggs Bacterial Environment. AB - Selective pressures imposed by pathogenic microorganisms to embryos have selected in hosts for a battery of antimicrobial lines of defenses that includes physical and chemical barriers. Due to the antimicrobial properties of volatile compounds of green plants and of chemicals of feather degrading bacteria, the use of aromatic plants and feathers for nest building has been suggested as one of these barriers. However, experimental evidence suggesting such effects is scarce in the literature. During two consecutive years, we explored experimentally the effects of these nest materials on loads of different groups of bacteria (mesophilic bacteria, Enterobacteriaceae, Staphylococcus and Enterococcus) of eggshells in nests of spotless starlings (Sturnus unicolor) at the beginning and at the end of the incubation period. This was also explored in artificial nests without incubation activity. We also experimentally increased bacterial density of eggs in natural and artificial nests and explored the effects of nest lining treatments on eggshell bacterial load. Support for the hypothetical antimicrobial function of nest materials was mainly detected for the year and location with larger average values of eggshell bacterial density. The beneficial effects of feathers and plants were more easily detected in artificial nests with no incubation activity, suggesting an active role of incubation against bacterial colonization of eggshells. Pigmented and unpigmented feathers reduced eggshell bacterial load in starling nests and artificial nest boxes. Results from artificial nests allowed us to discuss and discard alternative scenarios explaining the detected association, particularly those related to the possible sexual role of feathers and aromatic plants in starling nests. All these results considered together confirm the antimicrobial functionality mainly of feathers but also of plants used as nest materials, and highlight the importance of temporally and geographically environmental variation associated with risk of bacterial proliferation determining the strength of such effects. Because of costs associated to nest building, birds should adjust nest building effort to expected bacterial environments during incubation, a prediction that should be further explored. PMID- 26871452 TI - Primitive Genepools of Asian Pears and Their Complex Hybrid Origins Inferred from Fluorescent Sequence-Specific Amplification Polymorphism (SSAP) Markers Based on LTR Retrotransposons. AB - Recent evidence indicated that interspecific hybridization was the major mode of evolution in Pyrus. The genetic relationships and origins of the Asian pear are still unclear because of frequent hybrid events, fast radial evolution, and lack of informative data. Here, we developed fluorescent sequence-specific amplification polymorphism (SSAP) markers with lots of informative sites and high polymorphism to analyze the population structure among 93 pear accessions, including nearly all species native to Asia. Results of a population structure analysis indicated that nearly all Asian pear species experienced hybridization, and originated from five primitive genepools. Four genepools corresponded to four primary Asian species: P. betulaefolia, P. pashia, P. pyrifolia, and P. ussuriensis. However, cultivars of P. ussuriensis were not monophyletic and introgression occurred from P. pyrifolia. The specific genepool detected in putative hybrids between occidental and oriental pears might be from occidental pears. The remaining species, including P. calleryana, P. xerophila, P. sinkiangensis, P. phaeocarpa, P. hondoensis, and P. hopeiensis in Asia, were inferred to be of hybrid origins and their possible genepools were identified. This study will be of great help for understanding the origin and evolution of Asian pears. PMID- 26871454 TI - Sugammadex, airway obstruction, and drifting across the ethical divide: a personal account. PMID- 26871453 TI - TDM1 Regulation Determines the Number of Meiotic Divisions. AB - Cell cycle control must be modified at meiosis to allow two divisions to follow a single round of DNA replication, resulting in ploidy reduction. The mechanisms that ensure meiosis termination at the end of the second and not at the end of first division are poorly understood. We show here that Arabidopsis thaliana TDM1, which has been previously shown to be essential for meiotic termination, interacts directly with the Anaphase-Promoting Complex. Further, mutations in TDM1 in a conserved putative Cyclin-Dependant Kinase (CDK) phosphorylation site (T16-P17) dominantly provoked premature meiosis termination after the first division, and the production of diploid spores and gametes. The CDKA;1 CYCA1.2/TAM complex, which is required to prevent premature meiotic exit, phosphorylated TDM1 at T16 in vitro. Finally, while CYCA1;2/TAM was previously shown to be expressed only at meiosis I, TDM1 is present throughout meiosis. These data, together with epistasis analysis, lead us to propose that TDM1 is an APC/C component whose function is to ensure meiosis termination at the end of meiosis II, and whose activity is inhibited at meiosis I by CDKA;1-TAM-mediated phosphorylation to prevent premature meiotic exit. This provides a molecular mechanism for the differential decision of performing an additional round of division, or not, at the end of meiosis I and II, respectively. PMID- 26871455 TI - Quantitative Proteomics of the Infectious and Replicative Forms of Chlamydia trachomatis. AB - The obligate intracellular developmental cycle of Chlamydia trachomatis presents significant challenges in defining its proteome. In this study we have applied quantitative proteomics to both the intracellular reticulate body (RB) and the extracellular elementary body (EB) from C. trachomatis. We used C. trachomatis L2 as a model chlamydial isolate for our study since it has a high infectivity:particle ratio and there is an excellent quality genome sequence. EBs and RBs (>99% pure) were quantified by chromosomal and plasmid copy number using PCR, from which the concentrations of chlamydial proteins per bacterial cell/genome were determined. RBs harvested at 15h post infection (PI) were purified by three successive rounds of gradient centrifugation. This is the earliest possible time to obtain purified RBs, free from host cell components in quantity, within the constraints of the technology. EBs were purified at 48h PI. We then used two-dimensional reverse phase UPLC to fractionate RB or EB peptides before mass spectroscopic analysis, providing absolute amount estimates of chlamydial proteins. The ability to express the data as molecules per cell gave ranking in both abundance and energy requirements for synthesis, allowing meaningful identification of rate-limiting components. The study assigned 562 proteins with high confidence and provided absolute estimates of protein concentration for 489 proteins. Interestingly, the data showed an increase in TTS capacity at 15h PI. Most of the enzymes involved in peptidoglycan biosynthesis were detected along with high levels of muramidase (in EBs) suggesting breakdown of peptidoglycan occurs in the non-dividing form of the microorganism. All the genome-encoded enzymes for glycolysis, pentose phosphate pathway and tricarboxylic acid cycle were identified and quantified; these data supported the observation that the EB is metabolically active. The availability of detailed, accurate quantitative proteomic data will be invaluable for investigations into gene regulation and function. PMID- 26871456 TI - The effect of fathers' and mothers' educational level on adult oral health in Japan. AB - OBJECTIVES: Previous studies have shown that childhood socioeconomic status is associated with oral health in adulthood, but these studies have not examined the effects of fathers' and mothers' characteristics separately. Our objective was to examine the effects of fathers' and mothers' educational level on oral health in adulthood. METHODS: A questionnaire survey was conducted for community-dwelling adults aged 25-50 years. A total of 4385 agreed to participate and complete the survey. Self-rated oral health was used to evaluate current oral health. We conducted multiple logistic regression analyses to determine whether the fathers' or mothers' education was associated with current oral health after adjusting for the respondents' own education, current income, and childhood economic status. RESULTS: Among respondents, 29.7% of men and 23.0% of women reported their own oral health as fair or poor. Among men, both the fathers' and mothers' education were significantly associated with oral health after adjusting for other socioeconomic indicators. After including the fathers' and mothers' education into the model simultaneously, a significant association remained only for the mothers' education; those whose mothers' educational attainment was junior high school had significantly higher odds ratio for poor oral health (1.90, 95% confidence interval 1.13-3.18) compared with those whose mothers' educational attainment was university or higher. Among women, neither the fathers' nor mothers' education was associated with oral health. Both childhood and current economic statuses were associated with oral health among women. CONCLUSIONS: Parental education was associated with adult oral health only among men. Among men, the association was stronger for the mothers' education than for the fathers' education. Further research should explore underlying mechanisms by which parental education, especially the mothers' education, affects their sons' oral health in later life. PMID- 26871457 TI - Speckle Tracking Based Strain Analysis Is Sensitive for Early Detection of Pathological Cardiac Hypertrophy. AB - Cardiac hypertrophy is a key pathological process of many cardiac diseases. However, early detection of cardiac hypertrophy is difficult by the currently used non-invasive method and new approaches are in urgent need for efficient diagnosis of cardiac malfunction. Here we report that speckle tracking-based strain analysis is more sensitive than conventional echocardiography for early detection of pathological cardiac hypertrophy in the isoproterenol (ISO) mouse model. Pathological hypertrophy was induced by a single subcutaneous injection of ISO. Physiological cardiac hypertrophy was established by daily treadmill exercise for six weeks. Strain analysis, including radial strain (RS), radial strain rate (RSR) and longitudinal strain (LS), showed marked decrease as early as 3 days after ISO injection. Moreover, unlike the regional changes in cardiac infarction, strain analysis revealed global cardiac dysfunction that affects the entire heart in ISO-induced hypertrophy. In contrast, conventional echocardiography, only detected altered E/E', an index reflecting cardiac diastolic function, at 7 days after ISO injection. No change was detected on fractional shortening (FS), E/A and E'/A' at 3 days or 7 days after ISO injection. Interestingly, strain analysis revealed cardiac dysfunction only in ISO-induced pathological hypertrophy but not the physiological hypertrophy induced by exercise. Taken together, our study indicates that strain analysis offers a more sensitive approach for early detection of cardiac dysfunction than conventional echocardiography. Moreover, multiple strain readouts distinguish pathological cardiac hypertrophy from physiological hypertrophy. PMID- 26871458 TI - Association of hearing impairment with insulin resistance, beta-cell dysfunction and impaired fasting glucose before onset of diabetes. AB - AIM: Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance (IR), beta-cell dysfunction and impaired fasting glucose (IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population. METHODS: Participants included 1589 males and 2496 females, who were >= 20 years of age and without diabetes from the Korea National Health and Nutritional Examination Surveys of the Korean population (2010). Audiometric tests and laboratory examinations were performed. Homeostasis model assessments of IR and beta-cell function (HOMA-IR and HOMA-beta) were calculated. RESULTS: The prevalence of both high- and low-/mid-frequency hearing impairment among subjects with IFG was higher compared with those with normal glycaemia (42.2% vs. 24.5%, 14.7% vs. 7.8%, respectively). After adjustment for age, HOMA IR and HOMA-beta showed significant association with high-frequency hearing impairment in males. In the multiple logistic regression analyses adjusting for confounding variables, the presence of IFG, higher HOMA-IR and lower HOMA-beta remained as independent risk factors for high-frequency mild hearing impairment in males < 70 years [odds ratio (OR) 1.441, 95% confidence interval (95% CI), 1.056 to 1.967; OR, 1.448, 95% CI, 1.039 to 2.101; and OR, 0.447, 95% CI, 0.274 to 0.729, P < 0.05, respectively). CONCLUSIONS: IR, beta-cell dysfunction and IFG are associated with high-frequency mild hearing impairment in the male population < 70 years before the onset of diabetes. PMID- 26871459 TI - Chiral separation on various modified amino alcohol-derived HPLC chiral stationary phases. AB - 3,5-Dinitrobenzoyl chloride was previously used for the preparation of (R) phenylglycinol- and (S)-leucinol-derived chiral stationary phases. In this study, 3,5-bis(trifluoromethyl)benzoyl chloride, 2-furoyl chloride, 2-theonyl chloride, 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride, diphenylcarbamoyl chloride, and 1-adamantanecarbonyl chloride were used to prepare six new phenylglycinol-derived chiral stationary phases (CSPs) and five new leucinol derived CSPs. Using these 11 CSPs, chiral separation of nine pi-acidic amino acid derivatives and five pi-basic compounds was performed, and the separation results were compared. An adamantyl-derived CSP showed good separation. PMID- 26871461 TI - Quantification in Hyperpolarized NMR. AB - Quantitative aspects of hyperpolarized NMR are analyzed in the present work, and it is shown theoretically and experimentally that measured "apparent" signal enhancements could deviate significantly from real enhancements of polarization. Expressions are given as a function of spin count to deduce real enhancements from measured "apparent" enhancements, and vice versa. While the findings are of particular relevance to high-field work employing high-Q probes, and to analytical applications of hyperpolarized NMR whose objective is the measurement of spin count, our experiments demonstrate their significance even for low- and moderate-field work with probes of moderate Q-factor. PMID- 26871462 TI - Altered function of intracortical networks in chronic lateral epicondylalgia. AB - BACKGROUND: Lateral epicondylalgia (LE) is a musculotendinous condition characterized by persistent pain, sensorimotor dysfunction and motor cortex reorganization. Although there is evidence linking cortical reorganization with clinical symptoms in LE, the mechanisms underpinning these changes are unknown. Here we investigated activity in motor cortical (M1) intracortical inhibitory and facilitatory networks in individuals with chronic LE and healthy controls. METHODS: Surface electromyography was recorded bilaterally from the extensor carpi radialis brevis (ECRB) muscle of 14 LE (4 men, 41.5 +/- 9.9 years) and 14 control participants (4 men, 42.1 +/- 11.1 years). Transcranial magnetic stimulation of M1 was used to evaluate resting and active motor threshold, corticomotor output, short- (SICI) and long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) of both hemispheres. RESULTS: In individuals with LE, SICI (p = 0.005), ICF (p = 0.026) and LICI (p = 0.046) were less in the M1 contralateral to the affected ECRB muscle compared with healthy controls. Motor cortical threshold (rest: p = 0.57, active: p = 0.97) and corticomotor output (p = 0.15) were similar between groups. No differences were observed between individuals with LE and healthy controls for the M1 contralateral to the unaffected ECRB muscle. CONCLUSIONS: These data provide evidence of less intracortical inhibition mediated by both GABAA and GABAB receptors, and less intracortical facilitation in the M1 contralateral to the affected ECRB in individuals with LE compared with healthy controls. Similar changes were not present in the M1 contralateral to the unaffected ECRB. These changes may provide the substrate for M1 reorganization in chronic LE and could provide a target for future therapy. WHAT DOES THIS STUDY ADD: Lateral epicondylalgia (LE) is a common musculoskeletal condition characterized by elbow pain and sensorimotor dysfunction. The excitability and organization of the motor cortical representation of the wrist extensor muscles is altered in LE, but the mechanisms that underpin these changes are unknown. evidence of less intracortical inhibition mediated by both GABAA and GABAB receptors, and less intracortical facilitation mediated by NMDA receptors, in the M1 contralateral to the affected extensor carpi radialis brevis muscle in chronic LE compared with healthy controls. Altered activity in intracortical networks may contribute to altered motor cortex organization in LE and could provide a potential target for future treatments. PMID- 26871460 TI - Effects of meditation practice on spontaneous eyeblink rate. AB - A rapidly growing body of research suggests that meditation can change brain and cognitive functioning. Yet little is known about the neurochemical mechanisms underlying meditation-related changes in cognition. Here, we investigated the effects of meditation on spontaneous eyeblink rates (sEBR), a noninvasive peripheral correlate of striatal dopamine activity. Previous studies have shown a relationship between sEBR and cognitive functions such as mind wandering, cognitive flexibility, and attention-functions that are also affected by meditation. We therefore expected that long-term meditation practice would alter eyeblink activity. To test this, we recorded baseline sEBR and intereyeblink intervals (IEBI) in long-term meditators (LTM) and meditation-naive participants (MNP). We found that LTM not only blinked less frequently, but also showed a different eyeblink pattern than MNP. This pattern had good to high degree of consistency over three time points. Moreover, we examined the effects of an 8 week course of mindfulness-based stress reduction on sEBR and IEBI, compared to an active control group and a waitlist control group. No effect of short-term meditation practice was found. Finally, we investigated whether different types of meditation differentially alter eyeblink activity by measuring sEBR and IEBI after a full day of two kinds of meditation practices in the LTM. No effect of meditation type was found. Taken together, these findings may suggest either that individual difference in dopaminergic neurotransmission is a self-selection factor for meditation practice, or that long-term, but not short-term meditation practice induces stable changes in baseline striatal dopaminergic functioning. PMID- 26871463 TI - Family quality of life among families with a child who has a severe neurodevelopmental disability: Impact of family and child socio-demographic factors. AB - We aimed to examine family quality of life (FQOL) of Northern Israeli families having a child with a severe neurodevelopmental disability and its relation to socio-demographics. The cohort included caregivers of 70 children ages (mean +/- standard deviation) 5.36 +/- 3.53 years. Families were two-parent (85.7%), lived in the periphery (67.1%) and included Jews (60%), Muslims (18.6%), Druze (14.3%) and Christians (7.1%). Religiosity included: secular (38.6%), traditional (31.4%), religious (30%). Children's diagnosis included autistic spectrum disorder (41.4%), intellectual disability (21.4%), cerebral palsy (17.1%), genetic syndromes (17.1%) and sensorineural hearing loss (2.9%). Degree of support (1-minimal,5-greatest) required by the child was 3.67 +/- 1.28 for physical and 3.49 +/- 1.36 for communication. Primary caregivers completed the FQOL Survey. Domain scores were highest for family relations and lowest for financial well-being. Dimension scores were highest for importance and lowest for opportunities. Overall FQOL approximated average. Jewish families and residents of a major urban area reported higher and more religious families reported lower overall FQOL. Regression analysis found ethnicity contributing to overall FQOL and domain scores with residence contributing to support from services. Ethnicity and child dependence contributed to dimension scores. Northern Israeli families having a child with a severe neurodevelopmental disability report average FQOL scores. However, family and child dependence characteristics affect FQOL scores. Professionals working with these families should consider FQOL information when making recommendations. PMID- 26871464 TI - Developmental and physical-fitness associations with gross motor coordination problems in Peruvian children. AB - The aims of this cross-sectional study were to examine the developmental characteristics (biological maturation and body size) associated with gross motor coordination problems in 5193 Peruvian children (2787 girls) aged 6-14 years from different geographical locations, and to investigate how the probability that children suffer with gross motor coordination problems varies with physical fitness. Children with gross motor coordination problems were more likely to have lower flexibility and explosive strength levels, having adjusted for age, sex, maturation and study site. Older children were more likely to suffer from gross motor coordination problems, as were those with greater body mass index. However, more mature children were less likely to have gross motor coordination problems, although children who live at sea level or at high altitude were more likely to suffer from gross motor coordination problems than children living in the jungle. Our results provide evidence that children and adolescents with lower physical fitness are more likely to have gross motor coordination difficulties. The identification of youths with gross motor coordination problems and providing them with effective intervention programs is an important priority in order to overcome such developmental problems, and help to improve their general health status. PMID- 26871465 TI - HIF-3alpha1 promotes colorectal tumor cell growth by activation of JAK-STAT3 signaling. AB - Hypoxic environment is critical in colorectal cancer (CRC) development. Most studies have mainly focused on hypoxia-inducible factor (HIF)-1alpha and HIF 2alpha as the major hypoxic transcription factors in CRC development and progression. However, the role of HIF-3alpha in CRC is not clear. Here we found that HIF-3alpha protein was increased in colorectal tumors from both mouse models and human patients. Moreover, increased HIF-3alpha expression was correlated with decreased survival. Overexpression of a long isoform of HIF-3alpha, HIF-3alpha1, increased cell growth in two CRC cell lines. Surprisingly, overexpressed HIF 3alpha1 was localized to the cytosol and increased phosphorylated signal transducer and activator of transcription 3 (p-STAT3). STAT3 inhibition effectively reduced p-STAT3 levels and cell growth induced by HIF-3alpha1. The activation of p-STAT3 was independent of the transcriptional activity of HIF 3alpha1. However, the inhibition of the upstream regulator Janus kinase (JAK) abolished HIF-3alpha1-induced p-STAT3 and cell growth. Together, these results demonstrated that HIF-3alpha1 promotes CRC cell growth by activation of the JAK STAT3 signaling pathway through non-canonical transcription-independent mechanisms. PMID- 26871466 TI - Intercellular transfer of small RNAs from astrocytes to lung tumor cells induces resistance to chemotherapy. AB - Brain metastases are resistant to chemotherapy and carry a poor prognosis. Studies have shown that tumor cells are surrounded by activated astrocytes, whose cytoprotective properties they exploit for protection from chemotherapy-induced apoptosis. The mechanism of such astrocytic protection is poorly understood. A non-mutational mechanism of resistance to chemotherapy that is receiving increased attention is the regulation of gene translation mediated by small noncoding RNAs (sRNAs), and particularly microRNAs (miRNAs). With the aim of examining the role of astrocytic sRNAs in promoting resistance of human lung tumor PC14 cells to chemotherapy-induced apoptosis, here we used a miRNA microarray to compare sRNA profiles of human lung tumor cells cultured with and without astrocytes. We found that sRNAs are transferred from astrocytes to PC14 cells in a contact-dependent manner. Transfer was rapid, reaching a plateau after only 6 hours in culture. The sRNA transfer was inhibited by the broad-spectrum gap-junction antagonist carbenoxolone, indicating that transfer occurs via gap junctions. Among the transferred sRNAs were several that are implicated in survival pathways. Enforced expression of these sRNAs in PC14 cells increased their resistance to the chemotherapeutic agent paclitaxel. These novel findings might be of clinical relevance for the treatment of patients with brain metastases. PMID- 26871468 TI - Mutant p53 protects ETS2 from non-canonical COP1/DET1 dependent degradation. AB - Mutations in the tumor suppressor gene TP53 contribute to the development of approximately half of all human cancers. One mechanism by which mutant p53 (mtp53) acts is through interaction with other transcription factors, which can either enhance or repress the transcription of their target genes. Mtp53 preferentially interacts with the erythroblastosis virus E26 oncogene homologue 2 (ETS2), an ETS transcription factor, and increases its protein stability. To study the mechanism underlying ETS2 degradation, we knocked down ubiquitin ligases known to interact with ETS2. We observed that knockdown of the constitutive photomorphogenesis protein 1 (COP1) and its binding partner De etiolated 1 (DET1) significantly increased ETS2 stability, and conversely, their ectopic expression led to increased ETS2 ubiquitination and degradation. Surprisingly, we observed that DET1 binds to ETS2 independently of COP1, and we demonstrated that mutation of multiple sites required for ETS2 degradation abrogated the interaction between DET1 and ETS2. Furthermore, we demonstrate that mtp53 prevents the COP1/DET1 complex from ubiquitinating ETS2 and thereby marking it for destruction. Mechanistically, we show that mtp53 destabilizes DET1 and also disrupts the DET1/ETS2 complex thereby preventing ETS2 degradation. Our study reveals a hitherto unknown function in which DET1 mediates the interaction with the substrates of its cognate ubiquitin ligase complex and provides an explanation for the ability of mtp53 to protect ETS2. PMID- 26871467 TI - Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma. AB - HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment. PMID- 26871469 TI - Inverse agonist of estrogen-related receptor alpha suppresses the growth of triple negative breast cancer cells through ROS generation and interaction with multiple cell signaling pathways. AB - There is an urgent clinical need for targeted therapy approaches for triple negative breast cancer (TNBC) patients. Increasing evidences suggested that the expression of estrogen-related receptor alpha (ERRalpha) was correlate with unfavorable clinical outcomes of breast cancer patients. We here show that inhibition of ERRalpha by its inverse agonist XCT-790 can suppress the proliferation, decrease G2/M phases, and induce mitochondrial-related apoptosis of TNBC cells. XCT-790 elevates the proteins related to endoplasmic reticulum (ER) stress such as ATF4/6, XBT-1 and CHOP. It also increases the expression of growth inhibition related proteins such as p53 and p21. Further, XCT-790 can increase the generation of reactive oxygen species (ROS) in TNBC cells mainly through inhibition of SOD1/2. While ROS scavenger NAC abolishes XCT-790 induced ER-stress and growth arrest. XCT-790 treatment can rapidly activate the signal molecules including ERK1/2, p38-MAPK, JNK, Akt, p65, and IkappaBalpha, while NAC attenuates effects of XCT-790 induced phosphorylation of ERK1/2, p38-MAPK and Akt. Further, the inhibitors of ERK1/2, JNK, Akt, and NF-kappaB attenuate XCT-790 induced ROS generation. These data suggest that AKT/ROS and ERK/ROS positive feedback loops, NF-kappaB/ROS, and ROS/p38-MAPK, are activated in XCT-790 treated TNBC cells. In vivo experiments show that XCT-790 significantly suppresses the growth of MDA-MB-231 xenograft tumors, which is associated with up regulation of p53, p21, ER-stress related proteins while down regulation of bcl-2. The present discovery makes XCT-790 a promising candidate drug and lays the foundation for future development of ERRalpha-based therapies for TNBC patients. PMID- 26871471 TI - Exploiting machine learning for predicting skeletal-related events in cancer patients with bone metastases. AB - The aim of the bone metastases (BM) treatment is to prevent the occurrence of skeletal-related events (SREs). In clinical, physicians could only predict the occurrence of SREs by subjective experience. Machine learning (ML) could be used as predictive models in the medical field. But there is no published research using ML to predict SREs in cancer patients with BM. The purpose of this study was to assess the associations of clinical variables with the occurrence of SREs and to subsequently develop prediction models to help identify SREs risk groups.We analyzed 1143 cancer patients with BM. We used the statistical package of SPSS and SPSS Modeler for data analysis and the development of the prediction model. We compared the performance of logistic regression (LR), decision tree (DT) and support vector machine(SVM). The results suggested that Visual Analog Scale (VAS) scale was a key factor to SREs in LR, DT and SVM model. Modifiable factors such as Frankel classification, Mirels score, Ca, aminoterminal propeptide of type I collagen (PINP) and bone-specific alkaline phosphatase (BALP) were identified. We found that the result of applying LR, DT and SVM classification accuracy was 79.2%, 85.8% and 88.2%, with 9, 4 and 8 variables, respectively.In conclusion, DT and SVM achieved higher accuracies with smaller number of variables than the number of variables used in LR. ML techniques can be used to build model to predict SREs in cancer patients with BM. PMID- 26871470 TI - Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD 1/PD-L1 in high grade serous ovarian cancer. AB - Immune checkpoint inhibitors (e.g., anti-PD-1 and anti-PD-L1 antibodies) have demonstrated remarkable efficacy against hypermutated cancers such as melanomas and lung carcinomas. One explanation for this effect is that hypermutated lesions harbor more tumor-specific neoantigens that stimulate recruitment of an increased number of tumor-infiltrating lymphocytes (TILs), which is counterbalanced by overexpression of immune checkpoints such as PD-1 or PD-L1. Given that BRCA1/2 mutated high grade serous ovarian cancers (HGSOCs) exhibit a higher mutational load and a unique mutational signature with an elevated number of larger indels up to 50 bp, we hypothesized that they may also harbor more tumor-specific neoantigens, and, therefore, exhibit increased TILs and PD-1/PD-L1 expression. Here, we report significantly higher predicted neoantigens in BRCA1/2-mutated tumors compared to tumors without alterations in homologous recombination (HR) genes (HR-proficient tumors). Tumors with higher neoantigen load were associated with improved overall survival and higher expression of immune genes associated with tumor cytotoxicity such as genes of the TCR, the IFN-gamma and the TNFR pathways. Furthermore, immunohistochemistry studies demonstrated that BRCA1/2 mutated tumors exhibited significantly increased CD3+ and CD8+ TILs, as well as elevated expression of PD-1 and PD-L1 in tumor-associated immune cells compared to HR-proficient tumors. Survival analysis showed that both BRCA1/2-mutation status and number of TILs were independently associated with outcome. Of note, two distinct groups of HGSOCs, one with very poor prognosis (HR proficient with low number of TILs) and one with very good prognosis (BRCA1/2-mutated tumors with high number of TILs) were defined. These findings support a link between BRCA1/2 mutation status, immunogenicity and survival, and suggesting that BRCA1/2-mutated HGSOCs may be more sensitive to PD-1/PD-L1 inhibitors compared to HR-proficient HGSOCs. PMID- 26871472 TI - Loss of MEN1 activates DNMT1 implicating DNA hypermethylation as a driver of MEN1 tumorigenesis. AB - Multiple endocrine neoplasia type 1 (MEN1) syndrome results from mutations in the MEN1 gene and causes tumor formation via largely unknown mechanisms. Using a novel genome-wide methylation analysis, we studied tissues from MEN1-parathyroid tumors, Men1 knockout (KO) mice, and Men1 null mouse embryonic fibroblast (MEF) cell lines. We demonstrated that inactivation of menin (the protein product of MEN1) increases activity of DNA (cytosine-5)-methyltransferase 1 (DNMT1) by activating retinoblastoma-binding protein 5 (Rbbp5). The increased activity of DNMT1 mediates global DNA hypermethylation, which results in aberrant activation of the Wnt/beta-catenin signaling pathway through inactivation of Sox regulatory genes. Our study provides important insights into the role of menin in DNA methylation and its impact on the pathogenesis of MEN1 tumor development. PMID- 26871473 TI - Effectiveness of the Monte Carlo method in stereotactic radiation therapy applied to quasi-homogenous brain tumors. AB - This study was aimed to evaluate the effectiveness of Monte Carlo (MC) method in stereotactic radiotherapy for brain tumor. The difference in doses predicted by the conventional Ray-tracing (Ray) and the advanced MC algorithms was comprehensively investigated through the simulations for phantom and patient data, actual measurement of dose distribution, and the retrospective analysis of 77 brain tumors patients. These investigations consistently showed that the MC algorithm overestimated the dose than the Ray algorithm and the MC overestimation was generally increased as decreasing the beams size and increasing the number of beams delivered. These results demonstrated that the advanced MC algorithm would be inaccurate than the conventional Raytracing algorithm when applied to a (quasi ) homogeneous brain tumors. Thus, caution may be needed to apply the MC method to brain radiosurgery or radiotherapy. PMID- 26871474 TI - MALAT1 long ncRNA promotes gastric cancer metastasis by suppressing PCDH10. AB - EZH2, the catalytic component of polycomb repressive complex 2 (PRC2), is frequently overexpressed in human cancers and contributes to tumor initiation and progression, in part through transcriptional silencing of tumor suppressor genes. A number of noncoding RNAs (ncRNAs) recruit EZH2 to specific chromatin loci, where they modulate gene expression. Here, we used RNA immunoprecipitation sequencing (RIP-seq) to profile EZH2-associated transcripts in human gastric cancer cell lines. We identified 8,256 transcripts, including both noncoding and coding transcripts, some of which were derived from cancer-related loci. In particular, we found that long noncoding RNA (lncRNA) MALAT1 binds EZH2, suppresses the tumor suppressor PCDH10, and promotes gastric cellular migration and invasion. Our work thus provides a global view of the EZH2-associated transcriptome and offers new insight into the function of EZH2 in gastric tumorigenesis. PMID- 26871475 TI - Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib resistant melanoma in vivo. AB - The majority of human melanomas bears BRAF mutations and thus is treated with inhibitors of BRAF, such as vemurafenib. While patients with BRAF mutations often demonstrate an initial dramatic response to vemurafenib, relapse is extremely common. Thus, novel agents are needed for the treatment of these aggressive melanomas. Honokiol is a small molecule compound derived from Magnolia grandiflora that has activity against solid tumors and hematopoietic neoplasms. In order to increase the lipophilicity of honokiol, we have synthesized honokiol DCA, the dichloroacetate ester of honokiol. In addition, we synthesized a novel fluorinated honokiol analog, bis-trifluoromethyl-bis-(4-hydroxy-3-allylphenyl) methane (hexafluoro). Both compounds exhibited activity against A375 melanoma in vivo, but honokiol DCA was more active. Gene arrays comparing treated with vehicle control tumors demonstrated induction of the respiratory enzyme succinate dehydrogenase B (SDHB) by treatment, suggesting that our honokiol analogs induce respiration in vivo. We then examined its effect against a pair of melanomas, LM36 and LM36R, in which LM36R differs from LM36 in that LM36R has acquired vemurafenib resistance. Honokiol DCA demonstrated in vivo activity against LM36R (vemurafenib resistant) but not against parental LM36. Honokiol DCA and hexafluoro inhibited the phosphorylation of DRP1, thus stimulating a phenotype suggestive of respiration through mitochondrial normalization. Honokiol DCA may act in vemurafenib resistant melanomas to increase both respiration and reactive oxygen generation, leading to activity against aggressive melanoma in vivo. PMID- 26871476 TI - Clinical implications of TP53 mutations in myelodysplastic syndromes treated with hypomethylating agents. AB - We screened TP53 mutations in 168 MDS patients who were treated with HMA and evaluated predictive and prognostic value of TP53 mutations. Overall response to HMA was not different based on TP53 mutation status (45% vs. 32% in TP53-mutated and wild type [WT], respectively, P = 0.13). However, response duration was significantly shorter in TP53-mutated patients compared to WT patients (5.7 months vs. 28.5 months, P = 0.003). Longitudinal analysis of TP53 mutations after HMA showed that TP53 mutations almost always persisted at times of disease progression. TP53-mutated patients showed significantly worse overall survival (OS) compared to WT patients (9.4 months vs. 20.7 months, P <0.001). Further, TP53 mutations distinguished prognosis in the subgroup of patients with complex karyotype and Revised International Prognostic Scoring System (IPSS-R) defined very high-risk disease. Multivariate analysis showed that TP53 mutation status is significantly prognostic for OS after adjusting prognostic effect from other factors. The current study provides evidence that TP53 mutations are independently prognostic in MDS patients treated with HMA. While TP53-mutated MDS patients initially respond well to HMA, their duration of response is significantly shorter than WT patients. Novel strategies to improve duration of response in TP53-mutated MDS are urgently needed. PMID- 26871477 TI - MicroRNA-150 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting the GAB1-ERK axis. AB - MicroRNA-150 (miR-150) is frequently dysregulated in cancer and is involved in carcinogenesis and cancer progression. In this study, we found that miR-150 was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared to adjacent noncancerous tissues. Low levels of miR-150 were significantly associated with worse clinicopathological characteristics and a poor prognosis for patients with HCC. miR-150 overexpression inhibited cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo. Further experiments indicated that Grb2-associated binding protein 1 (GAB1) was a direct target of miR-150 in HCC cells. In addition, GAB1 expression was increased in HCC tissues and inversely correlated with miR-150 levels. Knockdown of GAB1 mimicked the tumor-suppressive effects of miR-150 overexpression on HCC cells, whereas restoration of GAB1 expression partially abolished the inhibitory effects. Moreover, miR-150 overexpression decreased GAB1 expression, subsequently downregulated phospho-ERK1/2 and suppressed epithelial-mesenchymal-transition (EMT). These effects caused by miR-150 overexpression were alleviated by exogenous GAB1 expression. Taken together, this study demonstrates that miR-150 may be useful as a prognostic marker and that the identified miR-150-GAB1-ERK axis is a potential therapeutic target for HCC. PMID- 26871480 TI - Cyclic (di)nucleotides: the common language shared by microbe and host. AB - Fluency in a common language allows individuals to convey information and carry out complex activities that otherwise would be difficult or even impossible without the benefit of shared communication. Cyclic (di)nucleotides have recently been recognized as such an accessible language understood by both microbe and the host, ever since remarkable progresses have revealed the molecular details of these nucleotide second messengers used in cellular communication systems. Though undergoing separate evolutionary pathways in prokaryotes and eukaryotes, cyclic (di)nucleotides enable microbes to influence host cells immediately and fiercely by modulating a variety of cellular activities. Here we highlight recent insights in cyclic (di)nucleotides and focus on the balancing of these indispensable signaling molecules by synthases and phosphodiesterases. PMID- 26871479 TI - G protein-coupled receptor GPR160 is associated with apoptosis and cell cycle arrest of prostate cancer cells. AB - G protein-coupled receptors (GPCRs) represent the largest membrane protein family implicated in the therapeutic intervention of a variety of diseases including cancer. Exploration of biological actions of orphan GPCRs may lead to the identification of new targets for drug discovery. This study investigates potential roles of GPR160, an orphan GPCR, in the pathogenesis of prostate cancer. The transcription levels of GPR160 in the prostate cancer tissue samples and cell lines, such as PC-3, LNCaP, DU145 and 22Rv1 cells, were significantly higher than that seen in normal prostate tissue and cells. Knockdown of GPR160 by lentivirus-mediated short hairpin RNA constructs targeting human GPR160 gene (ShGPR160) resulted in prostate cancer cell apoptosis and growth arrest both in vitro and in athymic mice. Differential gene expression patterns in PC-3 cells infected with ShGPR160 or scramble lentivirus showed that 815 genes were activated and 1193 repressed. Functional annotation of differentially expressed genes (DEGs) revealed that microtubule cytoskeleton, cytokine activity, cell cycle phase and mitosis are the most evident functions enriched by the repressed genes, while regulation of programmed cell death, apoptosis and chemotaxis are enriched significantly by the activated genes. Treatment of cells with GPR160 targeting shRNA lentiviruses or duplex siRNA oligos increased the transcription of IL6 and CASP1 gene significantly. Our data suggest that the expression level of endogenous GPR160 is associated with the pathogenesis of prostate cancer. PMID- 26871481 TI - Survival games at the dinner table: regulation of Enterobacterial virulence through nutrient sensing and acquisition. AB - The ability of bacterial pathogens to colonize specific host niches is largely dependent on acquisition of essential metabolites and co-factors for growth and sensing and adapting in response to specific environmental cues. Nutrient availability in host environments is strongly influenced by host physiology and immunity, diet, and competition with other members of the host microbiota. Rapid adaptation to environmental cues and nutrient availability is a hallmark of bacterial fitness and virulence. This adaptability requires complex regulatory networks that tightly link sensing of nutrient availability to expression of virulence genes accordingly. This review focuses on recent findings highlighting the ability of bacterial pathogens to compete for nutrient acquisition in the host-microbiota environment, and emphasizes key aspects mediating the multi tiered regulatory cascades that coordinately control nutrient sensing and expression of virulence genes in pathogenic Enterobacteria. PMID- 26871478 TI - Mutanome and expression of immune response genes in microsatellite stable colon cancer. AB - The aim of this study was to analyze the impact of the mutanome in the prognosis of microsatellite stable stage II CRC tumors. The exome of 42 stage II, microsatellite stable, colon tumors (21 of them relapse) and their paired mucosa were sequenced and analyzed. Although some pathways accumulated more mutations in patients exhibiting good or poor prognosis, no single somatic mutation was associated with prognosis. Exome sequencing data is also valuable to infer tumor neoantigens able to elicit a host immune response. Hence, putative neoantigens were identified by combining information about missense mutations in each tumor and HLAs genotypes of the patients. Under the hypothesis that neoantigens should be correctly presented in order to activate the immune response, expression levels of genes involved in the antigen presentation machinery were also assessed. In addition, CD8A level (as a marker of T-cell infiltration) was measured. We found that tumors with better prognosis showed a tendency to generate a higher number of immunogenic epitopes, and up-regulated genes involved in the antigen processing machinery. Moreover, tumors with higher T-cell infiltration also showed better prognosis. Stratifying by consensus molecular subtype, CMS4 tumors showed the highest association of expression levels of genes involved in the antigen presentation machinery with prognosis. Thus, we hypothesize that a subset of stage II microsatellite stable CRC tumors are able to generate an immune response in the host via MHC class I antigen presentation, directly related with a better prognosis. PMID- 26871482 TI - Cell cycle control in Alphaproteobacteria. AB - Alphaproteobacteria include many medically and environmentally important organisms. Despite the diversity of their niches and lifestyles, from free-living to host-associated, they usually rely on very similar mechanisms to control their cell cycles. Studies on Caulobacter crescentus still lay the foundation for understanding the molecular details of pathways regulating DNA replication and cell division and coordinating these two processes with other events of the cell cycle. This review highlights recent discoveries on the regulation and the mode of action of conserved global regulators and small molecules like c-di-GMP and (p)ppGpp, which play key roles in cell cycle control. It also describes several newly identified mechanisms that modulate cell cycle progression in response to stresses or environmental conditions. PMID- 26871483 TI - Evaluating differences in Pavlovian fear acquisition and extinction as predictors of outcome from cognitive behavioural therapy for anxious children. AB - BACKGROUND: Extinction is a key theoretical model of exposure-based treatments, such as cognitive behavioural therapy (CBT). This study examined whether individual differences in physiological responses and subjective stimulus evaluations as indices of fear extinction predicted response to CBT. METHODS: Thirty-two nonanxious comparisons and 44 anxious, 7-to-13-year-old children completed a Pavlovian conditioning and extinction task. Anxious children then completed group-based CBT. Skin conductance responses (SCRs) as well as subjective arousal and valence evaluations were measured in response to a conditioned stimulus paired with an aversive tone (CS+) and another conditioned stimulus presented alone (CS-). Both stimuli were presented alone during extinction. Diagnostic and symptom measures were completed before and after treatment. RESULTS: Like nonanxious comparisons, treatment responders did not acquire conditioned negative stimulus evaluations and displayed elevated SCRs that declined significantly across extinction trials. Nonresponders, by contrast, showed elevated negative stimulus evaluations of both CSs that were sensitive to extinction trials but showed no change in SCRs during extinction. Change in physiological but not evaluative indices of fear extinction predicted better treatment outcomes. CONCLUSIONS: Individual differences in evaluative and physiological indices of fear extinction might moderate response to CBT. PMID- 26871484 TI - Policy Analysis: Valuation of Ecosystem Services in the Southern Appalachian Mountains. AB - This study estimates the economic value of an increase in ecosystem services attributable to the reduced acidification expected from more stringent air pollution policy. By integrating a detailed biogeochemical model that projects future ecological recovery with economic methods that measure preferences for specific ecological improvements, we estimate the economic value of ecological benefits from new air pollution policies in the Southern Appalachian ecosystem. Our results indicate that these policies generate aggregate benefits of about $3.7 billion, or about $16 per year per household in the region. The study provides currently missing information about the ecological benefits from air pollution policies that is needed to evaluate such policies comprehensively. More broadly, the study also illustrates how integrated biogeochemical and economic assessments of multidimensional ecosystems can evaluate the relative benefits of different policy options that vary by scale and across ecosystem attributes. PMID- 26871485 TI - A Molten Salt Lithium-Oxygen Battery. AB - Despite the promise of extremely high theoretical capacity (2Li + O2 <-> Li2O2, 1675 mAh per gram of oxygen), many challenges currently impede development of Li/O2 battery technology. Finding suitable electrode and electrolyte materials remains the most elusive challenge to date. A radical new approach is to replace volatile, unstable and air-intolerant organic electrolytes common to prior research in the field with alkali metal nitrate molten salt electrolytes and operate the battery above the liquidus temperature (>80 degrees C). Here we demonstrate an intermediate temperature Li/O2 battery using a lithium anode, a molten nitrate-based electrolyte (e.g., LiNO3-KNO3 eutectic) and a porous carbon O2 cathode with high energy efficiency (~95%) and improved rate capability because the discharge product, lithium peroxide, is stable and moderately soluble in the molten salt electrolyte. The results, supported by essential state-of-the art electrochemical and analytical techniques such as in situ pressure and gas analyses, scanning electron microscopy, rotating disk electrode voltammetry, demonstrate that Li2O2 electrochemically forms and decomposes upon cycling with discharge/charge overpotentials as low as 50 mV. We show that the cycle life of such batteries is limited only by carbon reactivity and by the uncontrolled precipitation of Li2O2, which eventually becomes electrically disconnected from the O2 electrode. PMID- 26871486 TI - Stimuli-Responsive Codelivery of Oligonucleotides and Drugs by Self-Assembled Peptide Nanoparticles. AB - Ever more emerging combined treatments exploiting synergistic effects of drug combinations demand smart, responsive codelivery carriers to reveal their full potential. In this study, a multifunctional stimuli-responsive amphiphilic peptide was designed and synthesized to self-assemble into nanoparticles capable of co-bearing and -releasing hydrophobic drugs and antisense oligonucleotides for combined therapies. The rational design was based on a hydrophobic l-tryptophan-d leucine repeating unit derived from a truncated sequence of gramicidin A (gT), to entrap hydrophobic cargo, which is combined with a hydrophilic moiety of histidines to provide electrostatic affinity to nucleotides. Stimuli responsiveness was implemented by linking the hydrophobic and hydrophilic sequence through an artificial amino acid bearing a disulfide functional group (H3SSgT). Stimuli-responsive peptides self-assembled in spherical nanoparticles in sizes (100-200 nm) generally considered as preferable for drug delivery applications. Responsive peptide nanoparticles revealed notable nucleotide condensing abilities while maintaining the ability to load hydrophobic cargo. The disulfide cleavage site introduced in the peptide sequence induced responsiveness to physiological concentrations of reducing agent, serving to release the incorporated molecules. Furthermore, the peptide nanoparticles, singly loaded or coloaded with boron-dipyrromethene (BODIPY) and/or antisense oligonucleotides, were efficiently taken up by cells. Such amphiphilic peptides that led to noncytotoxic, reduction-responsive nanoparticles capable of codelivering hydrophobic and nucleic acid payloads simultaneously provide potential toward combined treatment strategies to exploit synergistic effects. PMID- 26871487 TI - Elevated congenital anomaly rates and incorporated cesium-137 in the Polissia region of Ukraine. AB - BACKGROUND: Investigations soon after the 1986 Chornobyl (Chernobyl in Russian) accident of exposed populations residing elsewhere in Europe led government and international agencies to conclude that exposures to cesium-137 (Cs-137) were not teratogenic. Our observations of elevated population rates of neural tube defects (NTDs) and microcephaly and microphthalmia (M/M) in the Rivne Province in Ukraine, which were among the highest in Europe, prompted this follow-up investigation inclusive of whole-body counts (WBCs) of Cs-137 among ambulatory patients and pregnant women residing in Polissia, the most polluted region in Rivne. METHODS: Yearly (2000-2012) population rates of NTDs and M/M and WBC patterns of ambulatory patients (2001-2010) and pregnant women (2011-2013) in Polissia and non-Polissia regions of Rivne were analyzed. RESULTS: The NTD and M/M population rates in Rivne remain elevated and are statistically significantly higher in Polissia than in non-Polissia. The WBCs among residents in Polissia are statistically significantly higher than among those from non-Polissia. CONCLUSION: NTD and M/M rates are highest in the Polissia region of Rivne and are among the highest in Europe. In Polissia, the WBCs of Cs-137 are above officially set permissible upper limits. The results are based on aggregate data of NTDs and M/Ms and average WBC values. Further investigations of causality of the high rates of NTDs and M/Ms are needed and urgent strengthening policies and implementations to reduce exposures to teratogens, in particular radioactive nuclides and alcohol, and consumption of folic acid supplements are indicated. PMID- 26871488 TI - Effect of tillage system on yield and weed populations of soybean ( Glycin Max L.). AB - Field experiment was conducted at Agricultural and Natural Resources Research Center of Golestan Province, Iran, to determine the effects of tillage system and weed management regime on yield and weed populations in soybean ( Glycin max L.). The experimental design was a split plot where the whole plot portion was a randomized complete block with three replicates. Main plots were tillage system: 1- No-till row crop seeding, 2- No-till seed drilling, 3- Tillage with disc harrow and drill planting, 4- Tillage with chisel packer and drill planting. The subplots were weed management regimes: 1-Weed control with herbicide application, 2- Hand weeding, 3- Herbicide application plus hand weeding, and 4- Non-weeding. Results indicated that the main effects of tillage system and weed management regime were significant for seed yield, pod number per plant, seed number per pod, weed density and biomass, while their interaction were significant only for weed density, weed biomass, and seed number per pod. The highest grain yields (3838 kg ha-1) were recorded for No-till row crop seeding. The highest seed yield (3877 kg ha-1) also was recorded for weed control with herbicide and hand weeding treatment, followed by hand weeding (3379 kg ha-1). PMID- 26871489 TI - First report of multiple anthelmintic resistance in nematodes of sheep in Colombia. AB - This study aimed to report the presence of parasites resistant to the most used anthelmintic drugs in sheep in Colombia. Four farms (denominated farm 1, 2, 3 and 4) were selected where the animals were not treated with anthelmintics for two months before the trial. Animals with faecal egg count (FEC) above 150 and of different ages were allocated into six groups, each consisting of at least 5 animals. The drugs and dosages used were: ivermectin 1% (0.2 mg/kg), albendazole 25% (5 mg/kg), fenbendazole 10% (5 mg/kg), levamisole 10% (5 mg/kg), and moxidectin 1% (0.2 mg/kg). Anthelmintic efficacy was determined by the FEC reduction test (FECRT) with a second sampling 14 days post-treatment. The efficacy of albendazole and fenbendazole at farm 1 was above 95%, which was different from the others farms. The FECRT indicated the presence of multidrug resistance in the other farms where no tested drugs showed activity higher than 79% (albendazole: 0 to 55%, fenbendazole: 51.4 to 76.6%, ivermectin: 67.3 to 93.1%, levamisole: 0 to 78.1%, and moxidectin: 49.2 to 64.1%).Haemonchus contortus was the predominant (96%) species, followed by a small presence of Trichostrongylus sp. (3%) andCooperia sp. (1%). Therefore, we report for the first time the existence of multiple anthelmintic resistance in gastrointestinal nematodes of sheep in Colombia. PMID- 26871490 TI - DNA damage and cytotoxicity in pathology laboratory technicians exposed to organic solvents. AB - The aim of this study was to evaluate potential DNA damage and cytotoxicity in pathology laboratory technicians exposed to organic solvents, mainly xylene. Peripheral blood and buccal cells samples were collected from 18 technicians occupationally exposed to organic solvents and 11 non-exposed individuals. The technicians were sampled at two moments: Monday and Friday. DNA damage and cytotoxicity were evaluated using the Comet Assay and the Buccal Micronucleus Cytome assay. Fifteen subjects (83.5%) of the exposed group to solvents complained about some symptom probably related to contact with vapours of organic solvents. DNA damage in the exposed group to solvents was nearly 2-fold higher on Friday than on Monday, and in both moments the individuals of this group showed higher levels of DNA damage in relation to controls. No statistical difference was detected in buccal cell micronucleus frequency between the laboratory technicians and the control group. However, in the analysis performed on Friday, technicians presented higher frequency (about 3-fold) of karyolytic and apoptotic like cells (karyorrhectic and pyknotic) in relation to control group. Considering the damage frequency and the working time, a positive correlation was found in the exposed group to solvents (r=0.468; p=0.05). The results suggest that pathology laboratory workers inappropriately exposed to organic solvents have increased levels of DNA damage. PMID- 26871491 TI - Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate. AB - The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest. PMID- 26871492 TI - Bioaccumulation of mercury, cadmium, zinc, chromium, and lead in muscle, liver, and spleen tissues of a large commercially valuable catfish species from Brazil. AB - The increasing amounts of heavy metals entering aquatic environments can result in high accumulation levels of these contaminants in fish and their consumers, which pose a serious risk to ecosystems and human health. We investigated the concentrations of mercury (Hg), cadmium (Cd), zinc (Zn), chromium (Cr), and lead (Pb) in muscle, liver, and spleen tissues of Pseudoplatystoma corruscans specimens collected from two sites on the Paraopeba River, Brazil. The level of heavy metals concentrations in the tissues was often higher in viscera (i.e. liver and spleen) than in muscle, and thus, the viscera should not be considered for human consumption. Correlations between metal concentrations and fish size were not significant. Although the levels of muscle bioaccumulation of Hg, Cd, Zn, Cr, and Pb, generally do not exceed the safe levels for human consumption, the constant presence of heavy metals in concentrations near those limits considered safe for human consumption, is a reason for concern, and populations who constantly consume fish from polluted rivers should be warned. Our findings also indicate that in a river network where certain areas are connected to other areas with high rates of environmental pollutants, people should be cautious about the regular consumption of fish, even when the fish consumed are caught in stretches of the basin where contamination levels are considered low, since many of the freshwater fish with high commercial value, such as the catfish surubim, are migratory. PMID- 26871493 TI - Ethanol reduces ripening of 'Royal Gala' apples stored in controlled atmosphere. AB - This work aims at evaluate ethanol effect of acetaldehyde application in post storage quality of 'Royal Gala' apples maintenance, and to compare them with consolidated storage techniques. Thus two experiments were performed during the years of 2008 and 2009. In the first experiment (2008), the application of ethanol, acetaldehyde or 1-MCP and ethylene scrubbing were tested. Fruits were stored in controlled atmosphere (CA) with 1.0kPa O2 and 2.0kPa CO2 at 0.5 degrees C. In the second experiment (2009), the treatments tested were ethanol application combined or not with low relative humidity (LRH) and LRH alone. In this experiment, apples were stored in CA with 1.2kPa O2 + 2.5kPa CO2 at 0.5 degrees C. After eight months of storage, 0.5 mL ethanol kg-1 apples month-1 or 0.25 mL acetaldehyde kg-1 apples month-1 increased mealiness, flesh browning, and decays incidence and reduced flesh firmness. In contrast, 0.3 mL ethanol kg-1 apples month-1, tested on second experiment, prevented fruit softening and decreased ACC oxidase activity and ethylene production. Although lower relative humidity was not efficient in maintaining post-storage quality, it enhanced the positive effect of ethanol application at 0.3 mL kg-1 apples month-1. PMID- 26871494 TI - Morpho-anatomy and ontogeny of the underground system of Chrysolaena simplex (Less.) Dematt. (Asteraceae). AB - The occurrence of thickened underground systems in Asteraceae is widely reported in the literature. Given the great complexity of underground systems, which may originate from roots, stems, or both, morpho-anatomical analyses are essential to ensure the use of correct terminology. The goals of this study were to describe the morpho-anatomy and ontogeny, investigate the occurrence of secondary metabolites and evaluate the effects of seasonality on the underground system of Chrysolaena simplex (Less.) Dematt. Samples were studied using standard protocols of plant anatomy, scanning electron microscopy, histochemical and phytochemical. The underground system of C. simplex was categorised as a rhizophore which started from cotyledonary node. In adult individuals, with rhizophores completely developed, the primary roots degenerated and adventitious radicular systems are formed. The buds in the subterranean portions promote the rhizophore growing, and form aerial stems when exposed to light. Lipophilic droplets were evident in the parenchymatous cells of the cortex and pith, endodermis and buds. Inulin-type fructans were observed in the stem axis and buds of the rhizophore. The presence of buds, secondary metabolites and the storage of fructans and lipids in the rhizophore can be seen as adaptive traits. PMID- 26871495 TI - Cytisus scoparius (Fam. Fabaceae) in southern Brazil - first step of an invasion process? AB - The occurrence of Scotch broom Cytisus scoparius (L.) Link (Fabaceae), is reported for the first time in Brazil. The species has been registered in the species-rich Campos Sulinos grasslands, in the Campos de Cima da Serra, and in the Serra do Sudeste. Naturalizing populations were frequently formed in natural habitats near to human settlements, where prevailing land uses and disturbances facilitate dispersal and establishment. The plant is an invasive species that has globally caused significant damage to biodiversity and economic losses. In Brazil, the species has a strong potential for spreading into a wide range of ecosystems. The Atlantic Forest biome and part of the Pampa biome, together known as the Campos Sulinos, represent optimal areas for the species. Features of the observed populations and recommendations for management are presented. PMID- 26871496 TI - High temperatures and absence of light affect the hatching of resting eggs of Daphnia in the tropics. AB - Temperature and light are acknowledged as important factors for hatching of resting eggs. The knowledge of how they affect hatching rates of this type of egg is important for the comprehension of the consequences of warming waters in recolonization of aquatic ecosystems dependent on dormant populations. This study aimed at comparing the influence of different temperature and light conditions on hatching rates of Daphnia ambigua andDaphnia laevis resting eggs from tropical environments. The ephippia were collected in the sediment of three aquatic ecosystems, in southeastern Brazil. For each lake, the resting eggs were exposed to temperatures of 20, 24, 28 and 32 degrees C, under light (12 h photoperiod) and dark conditions. The results showed that the absence of light and high temperatures have a negative influence on the hatching rates. Statistical differences for hatching rates were also found when comparing the studied ecosystems (ranging from 0.6 to 31%), indicating the importance of local environmental factors for diapause and maintenance of active populations. PMID- 26871497 TI - Ecology of the bromeligenous frog Phyllodytes luteolus (Anura, Hylidae) from three restinga remnants across Brazil's coast. AB - In this study, we analyzed diet, sexual dimorphism and bromeliad use in three populations of the hylid frog Phyllodytes luteolus from restinga habitats along the Brazilian coast. We found 13 arthropods categories in 161 stomachs. Ants and termites were the dominant prey items. The similar trophic niche across populations suggests this species has a conservative diet. We found sexual dimorphism regarding body size and jaw width. We recordedP. luteolus in five bromeliad species, but predominantly inAechmeablanchetiana (35.6% of individuals recorded). We recorded solitary individuals in 44% of occupied bromeliads, and never found two males sharing the same bromeliad. The data is suggestive that populations ofP. luteolus has a conservative diet independent of area, with ants and termites the being most relevant prey items. The sexual dimorphism in jaw and the solitary males may suggest that this species have territorial behavior. PMID- 26871498 TI - Intra-uterine experimental infection by Ureaplasma diversum induces TNF-alpha mediated womb inflammation in mice. AB - Ureaplasma diversum is an opportunistic pathogen associated with uterine inflammation, impaired embryo implantation, infertility, abortions, premature birth of calves and neonatal pneumonia in cattle. It has been suggested that the intra-uterine infection by Ureaplasma diversum can cause vascular changes that hinder the success of pregnancy. Thus, the aim of this study was to evaluate the changes of intrauterine site of A/J mice in estrus or proestrus phase inoculated with Ureaplasma diversum. The infection was monitored at 24, 48 and 72 hours by the PCR methodology to detect the Ureaplasma in the inoculation site and the profile of circulating blood cells. Morphological changes, intensity of inflammation and the production of cytokines were compared. The infected mice showed local inflammation through the production of IFN-gamma and TNF-alpha. Ureaplasma diversum infections in the reproductive tract of studied mice seemed to be associated with the production of pro-inflammatory cytokines in uterine parenchyma. The levels of TNF-alpha of infected mice were dependent on the bacterial load of inoculated Ureaplasma. Uterine experimental infections by Ureaplasma diversum have not been mentioned yet and herein we presented the first report of an intrauterine infection model in mice. PMID- 26871499 TI - Evaluation of antimicrobial activity of the endophytic actinomycete R18(6) against multiresistant Gram-negative bacteria. AB - Endophytic actinomycetes are promising sources of antimicrobial substances. This study evaluates the activity of metabolites produced by the endophytic actinomycete R18(6) against Gram-negative bacteria multiresistant to antimicrobials. R18(6) isolate was grown in submerged cultures under different conditions: carbon source, temperature, pH and incubation time to optimize antimicrobials production. The actinomycete grown in base medium supplemented with 1% glucose, pH 6.5 and incubation at 30 oC for 96 h with shaking at 100 rpm, exhibited the highest activity against the used Gram-negative bacteria. Minimum inhibitory concentration (MIC) of the crude extract produced by the microorganism varied between 1/32 and 1/256. It had bactericide or bacteriostatic activity, depending on the Gram-negative organism. The active extract was stable at high temperatures, and unstable in medium containing proteolytic enzymes. Micromorphology of R18(6) was investigated by optical and scan microscopy, revealing that it was morphologically similar to the genusStreptomyces. PMID- 26871501 TI - (4S)-4,8-dihydroxy-1-tetralone and other chemical constituents from Pestalotiopsis sp. EJC07, endophytic fromBauhinia guianensis. AB - The present work reports the isolation of eight compounds fromPestalotiopsis sp. EJC07 isolated as endophytic fromBauhinia guianensis, a tipical plant of the Amazon. The compounds (4S)-4,8-dihydroxy-1-tetralone (1), uracil (2), uridin (3), p-hydroxybenzoic acid (4), ergosterol (5), ergosterol peroxide (6), cerevisterol (7) and ducitol (8) were isolated by chromatographic procedures and identified by spectral methods of 1D and 2D NMR and MS. The compound 1 is being reported for the first time in the genusPestalotiopsis. PMID- 26871500 TI - Collaboration Networks in the Brazilian Scientific Output in Evolutionary Biology: 2000-2012. AB - This article analyzes the existing collaboration networks in the Brazilian scientific output in Evolutionary Biology, considering articles published during the period from 2000 to 2012 in journals indexed by Web of Science. The methodology integrates bibliometric techniques and Social Network Analysis resources to describe the growth of Brazilian scientific output and understand the levels, dynamics and structure of collaboration between authors, institutions and countries. The results unveil an enhancement and consolidation of collaborative relationships over time and suggest the existence of key institutions and authors, whose influence on research is expressed by the variety and intensity of the relationships established in the co-authorship of articles. International collaboration, present in more than half of the publications, is highly significant and unusual in Brazilian science. The situation indicates the internationalization of scientific output and the ability of the field to take part in the science produced by the international scientific community. PMID- 26871503 TI - Extremely efficient hydroboration of ketones and aldehydes by copper carbene catalysis. AB - A readily available copper carbene complex, (IPr)CuOtBu, catalyses the hydroboration of ketones and aldehydes even at very low catalyst loadings (0.1 mol%), in some cases with turnover frequencies exceeding 6000 h(-1). Carbonyl reduction occurs selectivitily in the presence of other reducible functional groups including alkenes, nitriles, esters, and alkyl chlorides. PMID- 26871502 TI - How does the stressed out ER find relief during virus infection? AB - The endoplasmic reticulum and Golgi network (ERGN) is vital to most cellular biosynthetic processes. Many positive strand RNA viruses depend upon the ERGN for replication, maturation, and egress. Viruses induce changes in ER architecture and stimulate fatty acid synthesis to create environments that can scaffold replication complexes, plant virus movement complexes, or virion maturation. Potato virus X (PVX) and Turnip mosaic virus (TuMV) each encode small membrane binding proteins that embed in the ERGN and activate the unfolded protein response (UPR). The UPR ensures ERGN homeostasis in the face of environmental assaults that could negatively impact the biosynthetic functions of the ERGN. This article explores the relationship between ER stress, the UPR, and membrane synthesis occurring during virus infection. PMID- 26871504 TI - Development of a Scalable Synthesis of Tofogliflozin. AB - An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography. PMID- 26871505 TI - Nitrogen redistribution and its relationship with the expression of GmATG8c during seed filling in soybean. AB - It is well known that some nitrogen in the vegetative organs is redistributed to the seeds during seed filling in soybean (Glycine max [L.] Merrill). This redistribution is considered to affect the seed yield of soybean. However, it is still not clear when the nitrogen moves from the vegetative part to the seeds, and the relationship between nitrogen redistribution and leaf senescence has not been clarified. The soybean variety Fukuyutaka was grown in the experimental field of Saga University, Japan from 22 July to 31 October, 2014. After the first flower stage (R1), the plant samples were collected weekly and were separated into leaf, petiole, stem, podshell and seed. The nitrogen concentrations in each plant part were determined. Fresh leaf samples were provided for the determination of soluble protein and autophagy gene GmATG8c expression. The nitrogen that accumulated in the vegetative parts reached its highest level at 60days after sowing (DAS), then began to decrease at 73DAS (R6). This decrease is considered to be the consequence of nitrogen redistribution from the vegetative parts to the seeds. The movement of nitrogen from the vegetative parts to the seeds was estimated to occur at around 73DAS (R6). At this stage, leaf SPAD values, leaf nitrogen, and soluble protein concentrations began to decrease simultaneously, suggesting the onset of leaf senescence. Furthermore, the expression of the autophagy gene GmATG8c in the leaves increased dramatically from 73 to 85DAS, which is the duration of nitrogen redistribution. The results suggest that the nitrogen redistribution from the vegetative parts to the seeds could be one of the initiating factors of leaf senescence, and the autophagy gene GmATG8c was associated with this process. PMID- 26871506 TI - Combined NMR and molecular dynamics modeling study of transport properties in sulfonamide based deep eutectic lithium electrolytes: LiTFSI based binary systems. AB - The trend toward Li-ion batteries operating at increased (>4.3 V vs. Li/Li(+)) voltages requires the development of novel classes of lithium electrolytes with electrochemical stability windows exceeding those of LiPF6/carbonate electrolyte solutions. Several new classes of electrolytes have been synthesized and investigated over the past decade, in the search for LIB electrolytes with improved properties (increased hydrolytic stability, improved thermal abuse tolerance, higher oxidation voltages, etc.) compared with the present state-of the-art LiPF6 and organic carbonates-based formulations. Among these are deep eutectic electrolytes (DEEs), which share many beneficial characteristics with ionic liquids, such as low vapor pressure and large electrochemical stability windows, with the added advantage of a significantly higher lithium transference number. The present work presents the pulsed field gradient NMR characterization of the transport properties (diffusion coefficients and cation transport numbers) of binary DEEs consisting of a sulfonamide solvent and lithium bis(trifluoromethanesulfonyl)imide salt. Insights into the structural and dynamical properties, which enable one to rationalize the observed ionic conductivity behavior were obtained from a combination of NMR data and MD simulations. The insights thus gained should assist the formulation of novel DEEs with improved properties for LIB applications. PMID- 26871507 TI - Carbon Quantum Dots Induced Ultrasmall BiOI Nanosheets with Assembled Hollow Structures for Broad Spectrum Photocatalytic Activity and Mechanism Insight. AB - Carbon quantum dots (CQDs) induced ultrasmall BiOI nanosheets with assembled hollow microsphere structures were prepared via ionic liquids 1-butyl-3 methylimidazolium iodine ([Bmim]I)-assisted synthesis method at room temperature condition. The composition, structure, morphology, and photoelectrochemical properties were investigated by multiple techniques. The CQDs/BiOI hollow microspheres structure displayed improved photocatalytic activities than pure BiOI for the degradation of three different kinds of pollutants, such as antibacterial agent tetracycline (TC), endocrine disrupting chemical bisphenol A (BPA), and phenol rhodamine B (RhB) under visible light, light above 580 nm, or light above 700 nm irradiation, which showed the broad spectrum photocatalytic activity. The key role of CQDs for the improvement of photocatalytic activity was explored. The introduction of CQDs could induce the formation of ultrasmall BiOI nanosheets with assembled hollow microsphere structure, strengthen the light absorption within full spectrum, increase the specific surface areas and improve the separation efficiency of the photogenerated electron-hole pairs. Benefiting from the unique structural features, the CQDs/BiOI microspheres exhibited excellent photoactivity. The h(+) was determined to be the main active specie for the photocatalytic degradation by ESR analysis and free radicals trapping experiments. The CQDs can be further employed to induce other nanosheets be smaller. The design of such architecture with CQDs/BiOI hollow microsphere structure can be extended to other photocatalytic systems. PMID- 26871508 TI - Diagnostic dilemma of sacral abscess presented with seizure and altered conscious level in a patient with spinal cord injury. AB - CONTEXT: Infection and septicaemia may clinically presented with seizure and altered conscious level. In spinal cord injury (SCI) population, they are at risk of having pressure ulcer which can be complicated further with infection and septicaemia. FINDINGS: A 40-year-old man with complete T4 SCI and multiple clean and non-healing pressure ulcers at sacral and bilateral ischial tuberosity regions was initially admitted for negative pressure wound therapy (NPWT) dressing. He had an episode of seizure and subsequently had fluctuating altered conscious level before the diagnosis of deep-seated sacral abscess was made and managed. Prior investigations to rule out common possible sources of infections and management did not resolve the fluctuating event of altered consciousness. CLINICAL RELEVANCE: We presented an unusual case presentation of septicemia in a patient with SCI with underlying chronic non-healing pressure ulcer. He presented with seizure and fluctuating altered conscious level. Even though a chronic non healing ulcer appeared clinically clean, a high index of suspicion for deep seated abscess is warranted as one of the possible sources of infection, especially when treatment for other common sources of infections fails to result in clinical improvement. PMID- 26871510 TI - Need for and Steps Toward a Clinical Guideline for the Telemental Healthcare of Children and Adolescents. AB - OBJECTIVE: This article identifies and describes key considerations toward the development of a clinical guideline intended to optimize telemental healthcare (TMH) of children and adolescents. METHODS: The literature was searched with key terms and title words. Of 2824 articles that met primary or secondary key word search criteria, 326 met both criteria, and 118 thematically related directly to child and adolescent TMH. Only 44 studies met levels of evidence I-III and expert recommendation criteria used in clinical guidelines; review of their references found 8 additional studies (52 total). Data from adult, child, and adolescent in person psychiatric care and adult TMH were applied to provide context in developing the key considerations. RESULTS: TMH guidelines for adults are well delineated, and TMH guidelines for children and adolescents are likely to closely overlap in terms of general clinical, technical, and administrative issues. However, for a child and adolescent focus, modifications of existing general guidelines appear necessary; for example, based on developmental status, family involvement, and patient-site modifications for space and sound. Additional clinical issues include specify who, exactly, is the "patient" (i.e., the patient, family, and /or other stakeholders), modalities of care (i.e., age related psychotherapies such as play therapy or behavior management), and psychopharmacology. CONCLUSIONS: Specific clinical, administrative, and technical issues are key considerations - based on the nuances of established child and adolescent mental healthcare - and must be considered in developing a clinical guideline for TMH of these patients. Developing such guidance should proceed from a careful review of the growing evidence base, and through expert consensus processes. PMID- 26871512 TI - Analysis of aDR5scFv with Specific Identification and Function. AB - Death receptor 5 (DR5) can selectively induce cell death in a wide variety of tumor cells. However, at least certain versions of the recombinant soluble TRAIL (sTRAIL) or anti-DR5 monoclonal antibody (mAb) are also shown to cause apoptosis in normal cells (especially in hepatocytes), hampering its clinical use for cancer therapy. Recently, the development of small recombinant antibody fragments as high-affinity therapeutic reagents with reduced immunogenicity has come under the spotlight. A popular format of engineered recombinant antibody fragment is the single-chain fixed-variable (scFv) molecule, in which the VH and VL regions of the parental antibody are joined by a polypeptide linker. The scFv fragment retains the target specificity and antigen binding affinity of the intact antibody, whereas it can be genetically designed and produced in large quantities by ectopically expressing both VH and VL regions from a single cDNA in cells. In this study, an aDR5scFv was constructed and expressed, and it was conformed so that it could recognize and bind eDR5 specifically. The therapeutic effects on human lung adenocarcinoma cells lines 973 in vitro and in vivo were detected by MTT assay, flow cytometry, hematoxylin and eosin staining, and TUNEL assay. aDR5scFv was able to induce 973 cell apoptosis in an in vitro system. The protein expressions of caspase-3, Bax, and cytochrome c were raised, and aDR5scFv also inhibited tumor growth in mice with its effect as well as with radiotherapy. It is concluded that aDR5scFv could possibly be considered as a novel therapeutic candidate for the treatment of tumors. PMID- 26871513 TI - Development and Characterization of Monoclonal Antibodies Against NS1 Protein of Duck Tembusu Virus. AB - To produce monoclonal antibodies (MAbs) against NS1 protein of duck Tembusu virus (TMUV), the NS1 gene sequence was cloned into the prokaryotic expression vector pET-28a(+). The prokaryotic protein NS1 was successfully expressed in BL21 (DE3) and used as the immunogen in mice. Six MAbs against NS1 protein were obtained by using the standard hybridoma technique. All MAbs can react with the denatured NS1 protein in the Western blot assay and the native NS1 protein from the TMUV infected BHK-21 cells in the immunofluorescence assay. The ELISA titers of the cell supernatants and ascites of MAbs were at a high level. The subtypes of the MAbs were determined by the Rapid Mouse Isotyping Kit-Gold series. Six MAbs possessed higher specificity and sensitivity, which indicated that MAbs against NS1 protein of TMUV may be used as valuable tools for analysis of the protein functions and pathogenesis of TMUV. PMID- 26871511 TI - Trastuzumab-Resistant Luminal B Breast Cancer Cells Show Basal-Like Cell Growth Features Through NF-kappaB-Activation. AB - A major clinical problem in the treatment of breast cancer is mortality due to metastasis. Understanding the molecular mechanisms associated with metastasis should aid in designing new therapeutic approaches for breast cancer. Trastuzumab is the main therapeutic option for HER2+ breast cancer patients; however, the molecular basis for trastuzumab resistance (TZR) and subsequent metastasis is not known. Earlier, we found expression of basal-like molecular markers in TZR tissues from patients with invasive breast cancer.(( 1 )) The basal-like phenotype is a particularly aggressive form of breast cancer. This observation suggests that TZR might contribute to an aggressive phenotype. To understand if resistance to TZR can lead to basal-like phenotype, we generated a trastuzumab resistant human breast cancer cell line (BT-474-R) that maintained human epidermal growth factor receptor 2 (HER2) overexpression and HER2 mediated signaling. Analysis showed that nuclear factor-kappa B (NF-kappaB) was constitutively activated in the BT-474-R cells, a feature similar to the basal like tumor phenotype. Pharmacologic inhibition of NF-kappaB improved sensitivity of BT-474-R cells to trastuzumab. Interestingly, activation of HER2 independent NF-kappaB is not shown in luminal B breast cancer cells. Our study suggests that by activating the NF-kappaB pathway, luminal B cells may acquire a HER2+ basal like phenotype in which NF-kappaB is constitutively activated; this notion is consistent with the recently proposed "progression through grade" or "evolution of resistance" hypothesis. Furthermore, we identified IKK-alpha/IKK-beta and nuclear accumulation of RelA/p65 as the major determinants in the resistant cells. Thus our study additionally suggests that the nuclear accumulation of p65 may be a useful marker for identifying metastasis-initiating tumor cells and targeting RelA/p65 may limit metastasis of breast and other cancers associated with NF-kappaB activation. PMID- 26871514 TI - Development and Characterization of Monoclonal Antibodies Specific for 3-(1 naphthoyl) Indole Derivatives. AB - 3-(1-naphthoyl) indole is one of the raw materials that synthesizes a synthetic cannabinoid such as 1-pentyl-3-(1-naphthoyl) indole (JWH-018) and 1-butyl-3-(1 naphthoyl) indole (JWH-073). It is important to detect the 3-(1-naphthoyl) indole derivatives rapidly, sensitively, and comprehensively. We developed two monoclonal antibodies (MAb) against 3-(1-naphthoyl) indole derivatives, named NT1 (IgG1) and NT2 (IgG1), which were possibly effective for detecting 3-(1 naphthoyl) indole derivatives. The cross-reactive ability of these MAbs was evaluated using a competitive enzyme-linked immunosorbent assay (ELISA). In the results, we found both of these antibodies recognize 3-(1-naphthoyl) indole and its derivatives. However neither of these antibodies recognize naphtoic acid, 4 methyl-naphtoic acid, and indole. Sixty to 100 nanomole per liter of 3-(1 naphthoyl) indole derivatives, such as 1-methyl-3-(1-naphthoyl) indole, 1-ethyl-3 (1-naphthoyl) indole, and 1-octyl-3-(1-naphthoyl) indole, can be detected using both of the obtained MAbs. Thus, the MAbs produced in this study could be a useful tool for the detection of 3-(1-naphthoyl) indole derivatives. PMID- 26871521 TI - Tungsten oxide nanowire synthesis from amorphous-like tungsten films. AB - A synthesis technique which can lead to direct integration of tungsten oxide nanowires onto silicon chips is essential for preparing various devices. The conversion of amorphous tungsten films deposited on silicon chips by pulsed layer deposition to nanowires by annealing is an apt method in that direction. This perspective discusses the ingenious features of the technique reported by Dellasega et al on the various aspects of tungsten oxide nanowire synthesis. PMID- 26871520 TI - Personalizing supportive care in oncology patients using pharmacogenetic-driven treatment pathways. AB - Cancer patients frequently suffer from disease- and treatment-related pain, nausea and depression, which severely reduces patients' quality of life. It is critical that clinicians are aware of drug-gene interactions and recognize the utility of applying pharmacogenetic information to personalize and improve supportive care. Pharmacogenetic-based algorithms may enhance clinical outcomes by allowing the clinician to select the 'least genetically vulnerable' drug. This review summarizes clinically relevant drug-gene interactions and presents pharmacogenetic-driven treatment pathways for depression, nausea/vomiting and pain. Ideally, this review provides a resource for clinicians to consult when selecting pharmacotherapy for a patient who presents with limited pharmacogenetic test results, with the hope of better controlling burdensome symptoms and improving the quality of life for cancer patients. PMID- 26871522 TI - A State-Level Assessment of Hospital-Based Palliative Care and the Use of Life Sustaining Therapies in the United States. AB - BACKGROUND: It is unknown how the prevalence of hospitals with palliative care programs (PCPs) at the state level in the United States correlates with the treatment of critically ill patients. OBJECTIVE: We examined the relationship between state-level PCP prevalence and commonly used treatments for critically ill patients as well as other public health metrics. METHODS: We compiled state level data for the year 2011 from multiple published sources. These included the poverty rate from the U.S. Census, public health measures such as the number of primary care physicians per 100,000 persons from America's Health Ranking website, and state-level rates for a series of validated ICD-9 (International Classification of Diseases, 9th Revision) procedure codes used for critically ill patients (e.g., prolonged acute mechanical ventilation [PAMV]) from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality. State-level percentages of PCPs came from a published report by the Center to Advance Palliative Care (CAPC). We used the Kruskal-Wallis test and Pearson's correlation coefficient for statistical inference. RESULTS: State-level poverty rates were negatively correlated with the percent of hospitals with PCPs: r = -0.39, p = 0.005. States with more hospital based PCPs had significantly lower rates of PAMV, tracheostomies, and hemodialysis but higher rates of nutritional support than states with fewer PCPs. CONCLUSIONS: States with more poverty and/or at high risk for delivering inefficient health care had fewer hospital PCPs. Hospital-based PCPs may influence the frequency of some interventions for critically ill patients. PMID- 26871524 TI - Notes from the Guest Editor. PMID- 26871523 TI - INTRAOCULAR PRESSURE IN PATIENTS WITH DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE INTRAVITREAL IMPLANT IN THE 3-YEAR MEAD STUDY. AB - PURPOSE: To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema treated with dexamethasone intravitreal implant (DEX implant). METHODS: Randomized, multicenter, 3-year, Phase III study. Patients (N = 1,048) with diabetic macular edema were randomized to DEX implant 0.7-mg, DEX implant 0.35 mg, or sham procedure with retreatment allowed at >=6-month intervals (seven injections maximum). RESULTS: In the DEX implant 0.7-mg, DEX implant 0.35-mg, and sham groups, respectively, >=10-mmHg IOP increases from baseline occurred in 27.7%, 24.8%, and 3.7% of patients, and their frequency did not increase with repeat injections. IOP-lowering medication was used by 41.5%, 37.6%, and 9.1% of patients. Only one patient (0.3%) in each DEX implant group had filtering surgery to manage a steroid-induced IOP increase. Among DEX implant 0.7-mg-treated patients with and without a >=10-mmHg IOP increase, 21.9% (21 of 96) and 22.4% (57 of 255), respectively, achieved >=15-letter best-corrected visual acuity gain at the end of the study, and mean average change in central retinal thickness from baseline was -127 MUm and -106 MUm, respectively. CONCLUSION: DEX implant demonstrated clear benefit of treatment despite increases in IOP. Sequential implants had no cumulative effect on IOP. PMID- 26871525 TI - Whose Death Is It Anyway? Perspectives on End-of-Life in Canada. AB - People die every minute in Canada, but how they die has become increasingly contentious as the demand for physician-assisted death and euthanasia has become louder and more widespread. Several events have propelled the debate around choice in end-of-life care, including the posthumous release of a video in which infectious disease expert Dr. Donald Low expressed his frustrations over his inability to control the manner of his death, the passing of Bill 52 in Quebec and the Supreme Court's decision to hear the Carter case challenging the constitutionality of the law against assisted suicide. Baby boomers are demanding more autonomy and choice in dying. Is the medical profession listening? PMID- 26871526 TI - Canadian Medical Association Perspectives on End-of-Life in Canada. AB - The Canadian Medical Association (CMA) is the representative body for the physicians of Canada. Over the past year, the association has been devoting significant time and resources to considering the important issues involved in care at the end of life. It has conducted a series of public town hall meetings across the country to allow Canadians to express their view on these issues, the only organization to have done so. The CMA will be appearing before the Supreme Court in the Carter case in October 2014 as a "friend of the court" and will continue to represent the views of the medical profession in these complex and difficult areas. PMID- 26871527 TI - "Speak Up, We Can't Hear You". AB - The author supports the lead authors' call for physicians to be open about their support for legalized assisted death. Citing evidence from Canada and internationally, the author demonstrates that support for euthanasia is growing in the medical community, and that many physicians would like to see legislative changes to support this trend. The commentary concludes with a call for physicians to educate themselves so that they can advocate more effectively on behalf of their patients. PMID- 26871528 TI - Why Don't More Physicians Support Assisted Death? AB - In this issue of Healthcare Papers, Maureen Taylor and Sandra Martin make a compelling case for the medical community to speak out in favour of physician assisted death (PAD) in Canada. As a member of the medical community, I want to echo that call to my colleagues. But I also want to explain my own evolution in thinking about PAD, in the hope that this will help non-physicians understand why this is such a difficult issue for physicians to tackle. I also hope that it will convince some of my colleagues to heed Taylor and Martin's call to speak out in favour of PAD. PMID- 26871529 TI - Why Am I Here? AB - In this essay I reflect on the meaning of death in life. Drawing on experiences as a practicing family physician providing care for dying patients and being witness to the deaths of family members, I argue for greater efforts to explicitly and openly support frank discussions about death and dying. I endorse the recommendations of the Royal Society of Canada expert panel, and point out remaining challenges that must be met regardless of whether there is a change in the legal structures regarding the permissibility of aid in dying. I conclude by arguing that understanding death in our lives helps shape its meaning and human significance. PMID- 26871530 TI - Assisted Dying in Canada. AB - This paper makes an affirmative ethical case in favour of the decriminalization of assisted dying in Canada. It then proceeds to defending the affirmative case against various slippery-slope arguments that are typically deployed by opponents of assisted dying. Finally, a recent case of questionable professional conduct by anti-euthanasia campaigners cum academics is flagged as a warning to all of us not to permit the quality of the professional debate to deteriorate unacceptably, despite the personal emotional investments involved on all sides of the debate. PMID- 26871531 TI - Increasing Interest and Demand? Is Our System Well-Enough Prepared for Policy Change? AB - The article co-authored by Maureen Taylor and Sandra Martin raises important issues that are resulting in new debate and attention in our thinking concerning physician-assisted death. It is likely that a change in policy is forthcoming, especially with the emerging force of a growing demographic who value personal choice and autonomy and are well-versed in the range of medical technologies and practices available. The issue of physician-assisted death cannot be understood apart from considering current models of healthcare and the role of adequate supportive care and psychosocial support. Despite having access to research and frameworks to inform quality palliative care, as well as communication competencies and guidelines to assist practitioners in the management of debilitating symptoms, our current healthcare system consists of healthcare professionals who continue to be challenged in their abilities to alleviate complex and challenging symptoms and distress. We will need to carefully assess our systems and plan well ahead for changes in policy to provide optimal, ethical and safe approaches to the offering of services around assisted death as an option for end-of-life care. PMID- 26871532 TI - Is It Time to Get MAD? AB - Like the rest of Canada, the vast majority of Quebecers do not have access to comprehensive, quality, palliative end-of-life care. Nevertheless, despite every substantive argument, compelling study, troubling precedent and cautionary tale regarding physician-hastened death, the Quebec Government has passed Bill 52 - a Bill legalizing euthanasia or what is euphemistically being called medical aid in dying (MAD). While the Bill purports to ensure that "everyone may have access, throughout the continuum of care, to quality care that is appropriate to their needs, including prevention and relief of suffering," it states that organizational structures, institutions and palliative care hospices will carry out this mandate "within the limits of the human, material and financial resources at their disposal." Perhaps, given the limitation of those resources, the only detail Bill 52 provides regarding how they will fulfill their mandate pertains to the administration and tracking of MAD. How will Quebecers feel when they realize that while their healthcare system can offer them euthanasia, it cannot assure them or their loved ones, access to healthcare professionals proficient in palliative care? All of which begs the question, is it really time to get MAD? PMID- 26871533 TI - Educating health professionals about evidence-based practice: still as important today as it was 20 years ago. PMID- 26871534 TI - Experimental manipulations of pain catastrophizing influence pain levels in patients with chronic pain and healthy volunteers. AB - Pain catastrophizing (PC) has been related to pain levels in both patients experiencing acute or chronic pain and in healthy volunteers exposed to experimental pain. Still, it is unclear whether high levels of pain catastrophizing lead to high levels of pain or vice versa. We therefore tested whether levels of pain catastrophizing could be increased and decreased in the same participant through hypnotic suggestions and whether the altered level of situation-specific pain catastrophizing was related to increased and decreased pain levels, respectively. Using the spontaneous pain of 22 patients with chronic tension-type headache and experimentally induced pain in 22 healthy volunteers, participants were tested in 3 randomized sessions where they received 3 types of hypnotic suggestions: Negative (based on the 13 items in the Pain Catastrophizing Scale), Positive (coping-oriented reversion of the Pain Catastrophizing Scale), and Neutral (neutral sentence) hypnotic suggestions. The hypnotic suggestions significantly increased and decreased situation-specific PC in both patients and healthy volunteers (P < 0.001). Also, the levels of pain intensity and pain unpleasantness were significantly altered in both patients and healthy volunteers (P < 0.001). Furthermore, regression analyses showed that changes in pain catastrophizing predicted changes in pain in patients (R = 0.204-0.304; P < 0.045) and in healthy volunteers (R = 0.328-0.252; P < 0.018). This is the first study to successfully manipulate PC in positive and negative directions in both patients with chronic pain and healthy volunteers and to show that these manipulations significantly influence pain levels. These findings may have important theoretical and clinical implications. PMID- 26871535 TI - Brain activations during pain: a neuroimaging meta-analysis of patients with pain and healthy controls. AB - In response to recent publications from pain neuroimaging experiments, there has been a debate about the existence of a primary pain region in the brain. Yet, there are few meta-analyses providing assessments of the minimum cerebral denominators of pain. Here, we used a statistical meta-analysis method, called activation likelihood estimation, to define (1) core brain regions activated by pain per se, irrelevant of pain modality, paradigm, or participants and (2) activation likelihood estimation commonalities and differences between patients with chronic pain and healthy individuals. A subtraction analysis of 138 independent data sets revealed that the minimum denominator for activation across pain modalities and paradigms included the right insula, secondary sensory cortex, and right anterior cingulate cortex (ACC). Common activations for healthy subjects and patients with pain alike included the thalamus, ACC, insula, and cerebellum. A comparative analysis revealed that healthy individuals were more likely to activate the cingulum, thalamus, and insula. Our results point toward the central role of the insular cortex and ACC in pain processing, irrelevant of modality, body part, or clinical experience; thus, furthering the importance of ACC and insular activation as key regions for the human experience of pain. PMID- 26871536 TI - Trends and predictors of opioid use after total knee and total hip arthroplasty. AB - Few studies have assessed postoperative trends in opioid cessation and predictors of persistent opioid use after total knee arthroplasty (TKA) and total hip arthroplasty (THA). Preoperatively, 574 TKA and THA patients completed validated, self-report measures of pain, functioning, and mood and were longitudinally assessed for 6 months after surgery. Among patients who were opioid naive the day of surgery, 8.2% of TKA and 4.3% of THA patients were using opioids at 6 months. In comparison, 53.3% of TKA and 34.7% of THA patients who reported opioid use the day of surgery continued to use opioids at 6 months. Patients taking >60 mg oral morphine equivalents preoperatively had an 80% likelihood of persistent use postoperatively. Day of surgery predictors for 6-month opioid use by opioid-naive patients included greater overall body pain (P = 0.002), greater affected joint pain (knee/hip) (P = 0.034), and greater catastrophizing (P = 0.010). For both opioid-naive and opioid users on the day of surgery, decreases in overall body pain from baseline to 6 months were associated with decreased odds of being on opioids at 6 months (adjusted odds ratio [aOR] = 0.72, P = 0.050; aOR = 0.62, P = 0.001); however, change in affected joint pain (knee/hip) was not predictive of opioid use (aOR = 0.99, P = 0.939; aOR = 1.00, P = 0.963). In conclusion, many patients taking opioids before surgery continue to use opioids after arthroplasty and some opioid-naive patients remained on opioids; however, persistent opioid use was not associated with change in joint pain. Given the growing concerns about chronic opioid use, the reasons for persistent opioid use and perioperative prescribing of opioids deserve further study. PMID- 26871537 TI - Twin-twin transfusion and laser therapy. AB - PURPOSE OF REVIEW: Twin-to-twin transfusion syndrome (TTTS) is an uncommon, but dangerous, complication of monochorionic diamniotic twin gestations. The purpose of this review is to provide an update on the evolving treatments in TTTS as it pertains primarily to laser photocoagulation, as well as to provide recently published information on outcomes. RECENT FINDINGS: The Solomon laser technique, in which selective fetoscopic laser photocoagulation is first performed and then followed by laser of the vascular equator from one side of the placenta to the other, reduces TTTS complications of twin anemia-polycythemia syndrome and recurrent TTTS. The addition of fetal echocardiography to the historical staging of TTTS adds important information that may guide future therapies. The postlaser ablation rate of neurodevelopmental delay in TTTS has recently been reported to be 14%. Cotwin demise is a significant complication of untreated TTTS and survival carries a 25% risk of cystic periventricular leukomalacia, middle cerebral artery infarction, and injury to other central nervous system structures as noted by neuroimaging. SUMMARY: Laser therapy for TTTS is clearly the only therapy that halts the disease process, allows both fetuses an opportunity to survive and protects a surviving cotwin in the event of the demise of one twin. Laser techniques have evolved greatly over the last 25 years and recent reports with the addition of the Solomon technique appearing to reduce some postlaser complications (twin anemia-polycythemia sequence and recurrent TTTS). Future focus of TTTS therapy should be centered on understanding the pathophysiology of the disease better with improvement in staging of the disease and on comparison of different laser techniques with the overall goal of not only increasing twin survival rates but also reducing long term neurodevelopmental morbidity. PMID- 26871538 TI - The continuing threat of syphilis in pregnancy. AB - PURPOSE OF REVIEW: Syphilis in pregnancy continues to be a worldwide threat to mothers and their fetuses, and in recent years has been increasing in prevalence. The purpose of this short review is to address current issues in the diagnosis and management of syphilis complicating pregnancies. RECENT FINDINGS: Maternal syphilis infections and congenital syphilis appear to be increasing in both high and low resource settings. Treponema pallidum ssp. pallidum, the causative spirochete of syphilis, remains one of the few human infectious pathogens that has not been successfully cultured, making identification difficult and research in targeted antimicrobial therapies challenging. Fortunately, syphilis remains sensitive to penicillin, which remains the foundational therapy for this infection. Patients with syphilis and significant penicillin allergies remain a specific challenge in treatment. Of concern is the emergence of T. pallidum resistant to macrolides such as azithromycin. This will limit options in patients with penicillin allergies, and potentially contribute to suboptimal treatment. During pregnancy, penicillin is the only known effective treatment for congenital syphilis, and pregnant patients with penicillin allergy should be desensitized and treated with penicillin. Research focusing on protein expression of the genome of T. pallidum may lead to more accurate screening and diagnosis and development of novel antibiotic therapies. SUMMARY: Obstetric and pediatric providers, public health organizations, and governments should recognize the re emergence of syphilis globally and in their local healthcare environments. Screening of all pregnant patients with robust treatment and follow-up represents the most effective method to reduce congenital syphilis currently available. PMID- 26871539 TI - [Intramedullary Stabilisation of Displaced Midshaft Clavicular Fractures in Heavy Workers and Complex Fracture Pattern]. AB - BACKGROUND: The medical literature recommends plate osteosynthesis (PO) for complex displaced midshaft clavicular fractures (DMCF) OTA type 15B3 and for heavy workers with displaced clavicular fractures. Recovery of DMCF treated with intramedullary stabilisation (IMS) will be examined and compared to published data for duration of inability to work (DIW) after conservative treatment as well as after PO, with respect to the DIW. PATIENTS AND METHODS: Between 09/2009 and 07/2015, the DIW of 58 patients (8 f, 50 m, mean age 38.4 [20-59] years) with DMCF treated with open reduction and IMS (Titanium Elastic Nail [TEN], Synthes, Umkirch, Germany) was determined. Inclusion criteria were the presence of closed unilateral DMCF and presence of a job with national insurance at the time of accident. DIW was counted in days, starting with the accident, and ending on the last day before resumption of full work. All patients were functionally treated for 6 weeks postoperatively without weights for the shoulder and with a maximum of 90 degrees abduction/flexion. The workload was classified in accordance with REFA criteria: group 0-1 (low physical workload) and group 2-4 (high physical workload). Fracture patterns (simple vs. complex) and postoperative physiotherapy (yes vs. no) were investigated for both REFA groups, as these factors may influence DIW. Fracture classification was performed in accordance with the OTA classification, as simple fractures (OTA type 15B1 and 15B2), and complex fractures (OTA type 15B3). Effects were concerned significant if p <= 0.05. RESULTS: Median DIW was independent of physical workload, with 39.86 (3-150) days (n = 58). Patients with low physical workload (REFA 0-1; n = 33) had shorter duration of DIW, with an average of 32.48 (3-136) days than patients with higher physical workload (REFA 2-4; n = 25), with 49.6 (14-150) days (p = 0.02). The fracture type did not influence this significantly (simple fractures [n = 35]: average 40.54 [3-150] days; complex fractures [n = 23]: average 38.82 [14-136] days, p = 0.85). Within each REFA group, differences in DIW for each fracture type were greater, but did not attain statistical significance. Patients without postoperative PT (n = 30) had a shorter DIW, with an average of 30.5 (3-84) days, than patients with postoperative PT (n = 28), with an average of 49.89 (14-150) days (p = 0.021). Within both REFA groups, DIW changed similarly with postoperative PT, in some cases with statistical significance. CONCLUSION: DIW after IMS of DMCF does not depend on the complexity of the fracture. For heavy workers, DIW after IMS is significantly longer than for light physical workers. IMS of DMCF permits immediate pain-adapted movement of the shoulder, with a maximal abduction/flexion up to 90 degrees , no matter what the fracture type. Patients given additional professional PT showed longer DIW than those without such treatment. PMID- 26871540 TI - [Bone Marrow Lesion - Risk-Factors and Pathophysiological Relevance: Systematic Review]. AB - AIM: The objective of this systematic review and meta-analysis is to obtain information about risks and associated factors for knee symptoms and the progression of osteoarthritis in idiopathic bone marrow lesion (BML). MATERIALS AND METHODS: The primary search on 31. 12. 2013 included the databases PubMed, EMBASE, Web of Science and Cochrane by the search strategy [[bone marrow edema] AND [knee]]. This review was continuously updated up to 31. 10. 2015. RESULTS: A total of 30 studies (from 1331 primary findings) were included in the final evaluation. The mean frequency of BML in all studies was 37.2 %. The occurrence of BML was strongly dependent on the MRI technique used (1.0 to 3.0 T). In longitudinal studies, the incidence of BML was 3.2 (95 % CI 1.7-6.3)/1000 person months. Weakly associated factors included female gender (OR = 1.3 [95 % CI 1.1 1.7], p = 0.009), increasing age (OR = 1.05 [95 % CI 0.9-1.3], p = 0.127), and overweight or obesity (OR = 1.1 [95 % CI 1.1-1.2]; p < 0.01). BMLs are significantly associated with cartilage lesions (OR = 5.5 [95 % CI 1.3-22.5]). Radiological osteoarthritis is also significantly associated with the development of BML (OR = 3.6 [95 % CI 1.2-10.6]) and the progression of osteoarthritis within a 3-year interval (OR = 4.4 [95 % CI 3.1-6.4]). CONCLUSIONS: The occurrence of BML is an important index for severe degenerative pathologies in the knee. It appears that MRT symptoms predict the progression of the disease. The clinical relevance and possible consequences for treatment are unclear. PMID- 26871542 TI - The magnetic monopole and the separation between fast and slow magnetic degrees of freedom. AB - The Landau-Lifshitz-Gilbert (LLG) equation that describes the dynamics of a macroscopic magnetic moment finds its limit of validity at very short times. The reason for this limit is well understood in terms of separation of the characteristic time scales between slow degrees of freedom (the magnetization) and fast degrees of freedom. The fast degrees of freedom are introduced as the variation of the angular momentum responsible for the inertia. In order to study the effect of the fast degrees of freedom on the precession, we calculate the geometric phase of the magnetization (i.e. the Hannay angle) and the corresponding magnetic monopole. In the case of the pure precession (the slow manifold), a simple expression of the magnetic monopole is given as a function of the slowness parameter, i.e. as a function of the ratio of the slow over the fast characteristic times. PMID- 26871543 TI - Agrobacterium-mediated transformation of Vitis Cv. Monastrell suspension-cultured cells: Determination of critical parameters. AB - Although some works have explored the transformation of differentiated, embryogenic suspension-cultured cells (SCC) to produce transgenic grapevine plants, to our knowledge this is one of the first reports on the efficient transformation of dedifferentiated Vitis vinifera cv Monastrell SCC. This protocol has been developed using the sonication-assisted Agrobacterium-mediated transformation (SAAT) method. A construct harboring the selectable nptII and the eyfp/IV2 marker genes was used in the study and transformation efficiencies reached over 50 independent transformed SCC per gram of infected cells. Best results were obtained when cells were infected at the exponential phase. A high density plating (500 mg/dish) gave significantly better results. As selective agent, kanamycin was inefficient for the selection of Monastrell transformed SCC since wild type cells were almost insensitive to this antibiotic whereas application of paromomycin resulted in very effective selection. Selected eyfp expressing microcalli were grown until enough tissue was available to scale up a new transgenic SCC. These transgenic SCC lines were evaluated molecularly and phenotypically demonstrating the presence and integration of both transgenes, the absence of Agrobacterium contamination and the ability of the transformed SCC to grow in highly selective liquid medium. The methodology described here opens the possibility of improving the production of valuable metabolites. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:725-734, 2016. PMID- 26871544 TI - Guess who? Children use prosody to infer intended listeners. AB - This study examined the relative influence of prosody and semantic content in children's inferences about intended listeners. Children (n = 72), who ranged in age from 5 to 10 years, heard greetings with prosody and content that was either infant or adult directed and chose the intended listener from amongst an infant or an adult. While content affected all children's choices, the effect of prosody was stronger (at least, for children aged 7-10 years). For conditions in which prosodic cues were suggestive of one listener, and content cues, another, children aged 7-10 years chose the listener according to prosody. In contrast, the youngest age group (5- to 6-year-olds) chose listeners at chance levels in these incongruent conditions. While prosodic cues were most influential in determining children's choices, their ratings of how certain they felt about their choices indicated that content nonetheless influenced their thinking about the intended listener. Results are the first to show the unique influence of prosody in children's thinking about appropriate speech styles. Findings add to work showing children's ability to use prosody to make inferences about speakers' communicative intentions. PMID- 26871545 TI - Prescribing or dispensing medication represents the best opportunity for GPs and pharmacists to engage older people in alcohol-related clinical conversations. AB - OBJECTIVES: This research aimed to identify older Australian drinkers' knowledge about Australian Alcohol Guidelines and their beliefs about the risks and benefits of alcohol; their recall of alcohol-related issues being raised with them by their community pharmacist and General Practitioner (GP); and their receptiveness to alcohol-related information being provided by either health professional. METHODS: This research was conducted in Perth, Western Australia. Flyers calling for participants were placed in local health and service centres, and advertisements were placed in local media. Participants who met eligibility requirements were posted a survey pack (n = 190) including an information letter, consent form, quantitative survey, and return addressed, postage paid envelope. 188 people aged over 60 years returned completed questionnaires. KEY FINDINGS: Women were more familiar with national alcohol guidelines, and were more conservative about the potential health benefits of alcohol. While 90% of participants were receptive to their GP asking about their alcohol use, only 30% of men and 20% of women recalled their GP raising this issue with them in the prior 12 months. Of these, high-risk drinkers were six times more likely than low risk drinkers to have been asked by their GP. Likewise, 50% of men and 65% of women were receptive to having alcohol-related health conversations with their community pharmacist, but less than 4% recalled their pharmacist raising this issue. Participants were most receptive to receiving information about alcohol medication interactions. CONCLUSIONS: This research highlights that prescribing and dispensing medication represents the ideal opportunity for health professionals to deliver alcohol-related information to older people. PMID- 26871541 TI - Colonoscopy Surveillance after Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. AB - The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance. PMID- 26871546 TI - A one-dimensional statistical mechanics model for nucleosome positioning on genomic DNA. AB - The first level of folding of DNA in eukaryotes is provided by the so-called '10 nm chromatin fibre', where DNA wraps around histone proteins (~10 nm in size) to form nucleosomes, which go on to create a zig-zagging bead-on-a-string structure. In this work we present a one-dimensional statistical mechanics model to study nucleosome positioning within one such 10 nm fibre. We focus on the case of genomic sheep DNA, and we start from effective potentials valid at infinite dilution and determined from high-resolution in vitro salt dialysis experiments. We study positioning within a polynucleosome chain, and compare the results for genomic DNA to that obtained in the simplest case of homogeneous DNA, where the problem can be mapped to a Tonks gas. First, we consider the simple, analytically solvable, case where nucleosomes are assumed to be point-like. Then, we perform numerical simulations to gauge the effect of their finite size on the nucleosomal distribution probabilities. Finally we compare nucleosome distributions and simulated nuclease digestion patterns for the two cases (homogeneous and sheep DNA), thereby providing testable predictions of the effect of sequence on experimentally observable quantities in experiments on polynucleosome chromatin fibres reconstituted in vitro. PMID- 26871547 TI - What Makes Health Systems Research in Developing Countries Ethical? Application of the Emanuel Framework for Clinical Research to Health Systems Research. AB - The growing importance of health systems research has opened debate about appropriate ethical frameworks and guidelines for the ethical review and conduct of health systems research. In this article we consider a detailed proposal from Hyder et al. (2014) and consider it in relation to the conventional criteria for ethics review of clinical research outlined by Emanuel et al. (2004; 2008) and argue that the Emanuel criteria can be usefully applied to the review of health systems research to supplement the Hyder et al. proposals. We argue further that health systems researchers and reviewers would benefit from many of the debates that have characterized the ethics of clinical research over the past three decades. PMID- 26871548 TI - Importance of different region-of-interest protocols for the apparent diffusion coefficient measurement of tumors in diffusion-weighted magnetic resonance imaging. PMID- 26871550 TI - A Pediatric Case of Sclerodermatous Graft-Versus-Host Disease Responsive to Ultraviolet A1 Phototherapy. AB - Graft-versus-host disease (GVHD) is one of the major complications after hematopoietic stem cell transplantation and is responsible for post-therapeutic morbidity, mortality, and poor quality of life of recipients. Sclerodermatous graft-versus-host disease (sGVHD) is a rare variant of chronic GVHD characterized by deposition of collagen in the skin and other soft tissues and resulting in loss of range of motion and functional capabilities. Treatment of sGVHD is challenging and largely limited by systemic side effects. Ultraviolet A1 phototherapy has been reported to be effective in connective tissue disorders, including sGVHD. We report a case of sGVHD in a 15-year-old girl that was resistant to traditional therapy but showed improvement in cutaneous symptoms with ultraviolet A1 phototherapy three times a week for 6 weeks (10 J/cm(2) single dose, 180 J/cm(2) cumulative dose). PMID- 26871549 TI - Non-volatile memory devices with redox-active diruthenium molecular compound. AB - Reduction-oxidation (redox) active molecules hold potential for memory devices due to their many unique properties. We report the use of a novel diruthenium based redox molecule incorporated into a non-volatile Flash-based memory device architecture. The memory capacitor device structure consists of a Pd/Al2O3/molecule/SiO2/Si structure. The bulky ruthenium redox molecule is attached to the surface by using a 'click' reaction and the monolayer structure is characterized by x-ray photoelectron spectroscopy to verify the Ru attachment and molecular density. The 'click' reaction is particularly advantageous for memory applications because of (1) ease of chemical design and synthesis, and (2) provides an additional spatial barrier between the oxide/silicon to the diruthenium molecule. Ultraviolet photoelectron spectroscopy data identified the energy of the electronic levels of the surface before and after surface modification. The molecular memory devices display an unsaturated charge storage window attributed to the intrinsic properties of the redox-active molecule. Our findings demonstrate the strengths and challenges with integrating molecular layers within solid-state devices, which will influence the future design of molecular memory devices. PMID- 26871551 TI - Fc Receptor Inhibition Reduces Susceptibility to Oxidative Stress in Human RPE Cells Treated with Bevacizumab, but not Aflibercept. AB - BACKGROUND/AIMS: VEGF-A is induced by oxidative stress, and functions as a survival factor for various cell types, including retinal pigment epithelial (RPE) cells. Anti-vascular endothelial growth factor (VEGF) drugs like aflibercept and bevacizumab have shown to be most effective in treating neovascular age-related macular degeneration (AMD), however uptake of the drugs might lead to interference with cell physiology. Herein, we evaluated the significance of the Fc receptor (FcR) within this context and moreover explored the impact of VEGF inhibition under normal conditions as well as under oxidative stress, in terms of potential adverse effects. METHODS: ARPE-19 (human RPE) cells were treated with aflibercept and bevacizumab in presence or absence of H2O2 as oxidative stress stimulus. After 24h cells were evaluated for drug uptake, VEGF-A expression and secretion, levels of intracellular reactive oxygen species (ROS) as well as cell proliferation. Experiments were repeated with cells being pre incubated with an FcR inhibitor prior to drug application. RESULTS: Both drugs inhibited extracellular levels of VEGF-A and were taken up into the RPE, resulting in significantly reduced intracellular levels of VEGF-A. When oxidative stress was applied, intracellular ROS levels in cells treated with both drugs rose, and cell proliferation was reduced. Prior incubation with the FcR inhibitor lessened the uptake of bevacizumab, but not aflibercept into RPE cells, and simultaneously enhanced cell survival under oxidative stress conditions. CONCLUSIONS: Our results indicate that uptake and accumulation of aflibercept and bevacizumab within RPE cells affect the intracellular VEGF-A metabolism negatively, leading to a biologically relevant reduced cell survival under oxidative stress. The FcR plays a substantial role in the uptake of bevacizumab, but not aflibercept, which allows an enhanced RPE cell survival through FcR blockage in an environment dominated by oxidative stress, as clinically significant for various inflammatory retinal disorders. PMID- 26871552 TI - In vivo human corneal deformation analysis with a Scheimpflug camera, a critical review. AB - Corneal morphological analysis has greatly improved in recent years, providing physicians with new and reliable parameters to study. Moreover, today corneal functional too is a routine analysis, thanks to biomechanical evaluation allowed by an ocular response analyzer (Reichert Ophthalmic Instrument, Depew, NY, USA). Corvis ST (OCULUS Optikgerate GmbH, Wetzlar, Germany), that relies on the ultrahigh speed Scheimpflug camera, is a new device providing corneal deformation parameters measured ny scanning the cornea response to an air puff; it is an instrument able to measure intraocular pressure too. This device could open up a whole new prospective in screening, detecting and managing corneal diseases, intraocular pressure measurement and in evaluating surgical procedures involving the cornea. This paper provides a comprehensive explanation of Corvis ST measurement principles and parameters and a literature review of scientific studies. PMID- 26871554 TI - In Situ Fluorine Doping of TiO2 Superstructures for Efficient Visible-Light Driven Hydrogen Generation. AB - With the aid of breakthroughs in nanoscience and nanotechnology, it is imperative to develop metal oxide semiconductors through visible light-driven hydrogen generation. In this study, TiOF2 was incorporated as an n-type F-dopant source to TiO2 mesocrystals (TMCs) with visible-light absorption during the topotactic transformation. The crystal growth, structural change, and dynamic morphological evolution, from the initial intermediate NH4 TiOF3 to HTiOF3, TiOF2, and F-doped TMCs, were verified through in situ temperature-dependent techniques to elucidate the doping mechanism from intermediate TiOF2. The visible-light efficiencies of photocatalytic hydrogen were dependent on the contents of the dopant as compared with the pure TMC and a controled reference. Using femtosecond time-resolved diffuse reflectance spectroscopy, the charge-transfer dynamics were monitored to confirm the improvement of charge separation after doping. PMID- 26871553 TI - Safety and Efficacy of Banaba-Moringa oleifera-Green Coffee Bean Extracts and Vitamin D3 in a Sustained Release Weight Management Supplement. AB - This 60-day, 30-subject pilot study examined a novel combination of ingredients in a unique sustained release (Carbopol matrix) tablet consumed twice daily. The product was composed of extracts of banaba leaf, green coffee bean, and Moringa oleifera leaf and vitamin D3. Safety was assessed using a 45-measurement blood chemistry panel, an 86-item self-reported Quality of Life Inventory, bone mineral density, and cardiovascular changes. Efficacy was assessed by calculating a body composition improvement index (BCI) based on changes in dual energy X-ray absorptiometry measured fat mass (FM) and fat-free mass (FFM) as well as between the study group (SG) and a historical placebo group. No changes occurred in any blood chemistry measurements. Positive changes were found in the Quality of Life (QOL) inventory composite scores. No adverse effects were observed. Decreases occurred in FM (p = 0.004) and increases in FFM (p = 0.009). Relative to the historical placebo group, the SG lost more FM (p < 0.0001), gained more FFM (p = <0.0001), and had a negative BCI of -2.7 lb. compared with a positive BCI in the SG of 3.4 lb., a 6.1 discordance (p = 0.0009). The data support the safety and efficacy of this unique product and demonstrate importance of using changes in body composition versus scale weight and BMI. PMID- 26871555 TI - Ambient temperature and risk of cardiovascular hospitalization: An updated systematic review and meta-analysis. AB - The association between temperatures and risk of cardiovascular mortality has been recognized but the association drawn from previous meta-analysis was weak due to the lack of sufficient studies. This paper presented a review with updated reports in the literature about the risk of cardiovascular hospitalization in relation to different temperature exposures and examined the dose-response relationship of temperature-cardiovascular hospitalization by change in units of temperature, latitudes, and lag days. The pooled effect sizes were calculated for cold, heat, heatwave, and diurnal variation using random-effects meta-analysis, and the dose-response relationship of temperature-cardiovascular admission was modelled using random-effect meta-regression. The Cochrane Q-test and index of heterogeneity (I(2)) were used to evaluate heterogeneity, and Egger's test was used to evaluate publication bias. Sixty-four studies were included in meta analysis. The pooled results suggest that for a change in temperature condition, the risk of cardiovascular hospitalization increased 2.8% (RR, 1.028; 95% CI, 1.021-1.035) for cold exposure, 2.2% (RR, 1.022; 95% CI, 1.006-1.039) for heatwave exposure, and 0.7% (RR, 1.007; 95% CI, 1.002-1.012) for an increase in diurnal temperature. However no association was observed for heat exposure. The significant dose-response relationship of temperature - cardiovascular admission was found with cold exposure and diurnal temperature. Increase in one-day lag caused a marginal reduction in risk of cardiovascular hospitalizations for cold exposure and diurnal variation, and increase in latitude was associated with a decrease in risk of cardiovascular hospitalizations for diurnal temperature only. There is a significant short-term effect of cold exposure, heatwave and diurnal variation on cardiovascular hospitalizations. Further research is needed to understand the temperature-cardiovascular relationship for different climate areas. PMID- 26871556 TI - Characteristics of extended-spectrum beta-lactamase (ESBL)- and pAmpC beta lactamase-producing Enterobacteriaceae of water samples in Tunisia. AB - The presence of extended-spectrum beta-lactamase and plasmid-mediated AmpC beta lactamase producing Enterobacteriaceae (ESBL-Eb and pAmpC-Eb, respectively) was analyzed in 57 wastewater and 57 surface-water samples in Tunisia. Twenty-four of the 57 wastewater samples (42.1%) and one of the 57 surface-water samples (1.7%, a river that received effluents of a wastewater-treatment-plant) contained ESBL Eb or pAmpC-Eb; one ESBL/pAmpC-Eb per positive sample was further characterized. Beta-lactamase genes detected were as follows: blaCTX-M-1 (10 Escherichia coli),blaCTX-M-15 (eight E. coli, one Klebsiella pneumoniae, one Citrobacter freundii), blaCTX-M-14 (one E. coli) and blaCMY-2 (four E. coli). The blaTEM-1, blaOXA-1 or blaSHV-1 genes were also found in 72% of these isolates. The ISEcp1, orf477 or IS903 sequences were found upstream or downstream of blaCTX-M genes. Class 1 integrons were present in 16 of the 25 ESBL-Eb/pAmpC-Eb strains (64%), and contained five different gene-cassette arrays. Most of the strains (76%) showed a multiresistant phenotype and qnr genes were identified in four strains. Molecular typing of ESBL/CMY-2-producing E. coli isolates showed 23 different PFGE-patterns and 15 different sequence-types (ST10, ST46, ST48, ST58, ST69, ST101, ST117, ST131, ST141, ST288, ST359, ST399, ST405, ST617, and the new ST4530); these strains were ascribed to phylogroups A (11 isolates), B1 (3 isolates), D (6 isolates) and B2 (3 isolates). From one to five plasmids were detected in each strain (size from 30kb to >240kb) and ESBL or pAmpC genes were transferred by conjugation in 69.5% of the E. coli strains. In conclusion, ESBL Eb and pAmpC-Eb strains are frequently detected in wastewater samples and they might be a source for dissemination in other environments with repercussion in public health. PMID- 26871557 TI - Control of sulfide and methane production in anaerobic sewer systems by means of Downstream Nitrite Dosage. AB - Bioproduction of hydrogen sulfide (H2S) and methane (CH4) under anaerobic conditions in sewer pipes causes detrimental effects on both sewer facilities and surrounding environment. Among the strategies used to mitigate the production of both compounds, the addition of nitrite (NO2(-)) has shown a greater long-term inhibitory effect compared with other oxidants such as nitrate or oxygen. The aim of this study was to determine the effectiveness of a new method, the Downstream Nitrite Dosage strategy (DNO2D), to control H2S and CH4 emissions in sewers. Treatment effectiveness was assessed on H2S and CH4 abatement on the effluent of a laboratory sewer pilot plant that mimics a full-scale anaerobic rising sewer. The experiment was divided in three different periods: system setup (period 1), nitrite addition (period 2) and system recovery (period 3). Different process and molecular methods were combined to investigate the impact of NO2(-) addition on H2S and CH4 production. Results showed that H2S load was reduced completely during nitrite addition when compared to period 1 due to H2S oxidation but increased immediately after nitrite addition stopped. The H2S overproduction during recovery period was associated with the bacterial reduction of different sulfur species (elemental sulfur/thiosulfate/sulfite) accumulated within the sewer biofilm matrix. Oxidation of CH4 was also detected during period 2 but, contrary to sulfide production, re-establishment of methanogenesis was not immediate after stopping nitrite dosing. The analysis of bulk and active microbial communities along experimental treatment showed compositional changes that agreed with the observed dynamics of chemical processes. Results of this study show that DNO2D strategy could significantly reduce H2S and CH4 emissions from sewers during the addition period but also suggest that microbial agents involved in such processes show a high resilience towards chemical stressors, thus favoring the re-establishment of H2S and CH4 production after stopping nitrite addition. PMID- 26871558 TI - Prospective Evaluation of a Panel of Plasma Cytokines and Chemokines as Potential Markers of Pelvic Endometriosis in Symptomatic Women. AB - BACKGROUND: Endometriosis is a chronic inflammatory disease for which no accurate peripheral diagnostic marker is available. Many cytokines and chemokines have been found altered in the plasma and peritoneal fluid of women with endometriosis compared to healthy controls, but little is known about their diagnostic utility to confirm or discard endometriosis among symptomatic women. OBJECTIVE: The study aims to assess the diagnostic value of a panel of plasma cytokines and chemokines to detect endometriosis in women undergoing laparoscopy for gynecological complains. METHODS: We performed a prospective cohort study evaluating simultaneously plasma concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 in 75 symptomatic women (chronic pelvic pain, infertility or ovarian cyst) submitted to laparoscopy. Assays were performed by Cytometric Bead Array System. Endometriosis was confirmed by histopathological examination of surgical specimens. RESULTS: Plasma IL-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 concentrations were not able to distinguish the women who eventually were diagnosed with endometriosis. CONCLUSION: Although previously shown to be altered in women with endometriosis compared to healthy women, the tested cytokines and chemokines were not useful to predict the presence of endometriosis among symptomatic women. This finding suggests that inflammatory markers modified by endometriosis may also be altered by other conditions associated with similar symptoms, which limits their use in clinical practice. PMID- 26871559 TI - A Novel SRY Gene Mutation p.F109L in a 46,XY Female with Complete Gonadal Dysgenesis. AB - 46,XY complete gonadal dysgenesis (CGD) is a disorder of sexual development that can result from different mutations in genes associated with sex determination. Patients are phenotypically females, and the disease is often diagnosed in late adolescence because of delayed puberty. Here, we present the clinical and molecular data of a 46,XY female CGD patient with gonadoblastoma with dysgerminoma and incidentally found inherited thrombophilia. The clinical significance of the described de novo SRY gene mutation c.325T>C (p.F109L) is discussed. This case report supports the critical role of the HGM domain in the SRY gene and the need of a multidisciplinary approach for CGD patients. PMID- 26871560 TI - Distribution of Dengue Virus Types 1 and 4 in Blood Components from Infected Blood Donors from Puerto Rico. AB - BACKGROUND: Dengue is a mosquito-borne viral disease caused by the four dengue viruses (DENV-1 to 4) that can also be transmitted by blood transfusion and organ transplantation. The distribution of DENV in the components of blood from infected donors is poorly understood. METHODS: We used an in-house TaqMan qRT-PCR assay to test residual samples of plasma, cellular components of whole blood (CCWB), serum and clot specimens from the same collection from blood donors who were DENV-RNA-reactive in a parallel blood safety study. To assess whether DENV RNA detected by TaqMan was associated with infectious virus, DENV infectivity in available samples was determined by culture in mosquito cells. RESULTS: DENV RNA was detected by TaqMan in all tested blood components, albeit more consistently in the cellular components; 78.8% of CCWB, 73.3% of clots, 86.7% of sera and 41.8% of plasma samples. DENV-1 was detected in 48 plasma and 97 CCWB samples while DENV-4 was detected in 21 plasma and 31 CCWB samples. In mosquito cell cultures, 29/111 (26.1%) plasma and 32/97 (32.7%) CCWB samples were infectious. A subset of samples from 29 donors was separately analyzed to compare DENV viral loads in the available blood components. DENV viral loads did not differ significantly between components and ranged from 3-8 log10 PCR-detectable units/ml. CONCLUSIONS: DENV was present in all tested components from most donors, and viral RNA was not preferentially distributed in any of the tested components. Infectious DENV was also present in similar proportions in cultured plasma, clot and CCWB samples, indicating that these components may serve as a resource when sample sizes are limited. However, these results suggest that the sensitivity of the nucleic acid tests (NAT) for these viruses would not be improved by testing whole blood or components other than plasma. PMID- 26871564 TI - Course and predictors of pain and physical functioning in patients with hip osteoarthritis: Systematic review and meta-analysis. AB - OBJECTIVE: To systematically summarize the literature on: (i) the course of pain and physical functioning; and (ii) predictors of deterioration of pain and physical functioning in patients with osteoarthritis of the hip. METHODS: A literature search was conducted in PubMed, CINAHL, Embase, PsychINFO and SPORTDiscus up to July 2015. Meta-analyses and qualitative data syntheses were performed. RESULTS: Eleven of the 15 included studies were of high quality. With regard to the course of pain and physical functioning, high heterogeneity was found across studies (I2 > 71%) and within study populations (reflected by large standard deviations (SDs) of change scores). Therefore, the course of pain and physical functioning was interpreted to be indistinct. Clinical characteristics (higher comorbidity count and presence of knee osteoarthritis), health behaviour factors (no supervised exercise and physical inactivity) and socio-demographics (lower education) were found to predict deterioration of pain (weak evidence). Higher comorbidity count and lower vitality were found to predict deterioration of physical functioning (strong evidence). For several other predictive factors weak evidence was found (e.g. bilateral hip pain, increase in hip pain (change), bilateral knee pain, presence of knee osteoarthritis). CONCLUSION: Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. Several clinical characteristics, health behaviours and psychosocial factors prognosticate deterioration of pain and physical functioning. These findings may guide future research aimed at the identification of subgroups of patients with hip osteoarthritis. PMID- 26871562 TI - Umbilical Cord Blood Transplantation Is a Feasible Rescue Therapeutic Option for Patients Suffering from Graft Failure after Previous Hematopoietic Stem Cell Transplantation. AB - OBJECTIVE: Umbilical cord blood (UCB) is an important graft source for hematopoietic stem cell transplantation (SCT). Due to less stringent human leukocyte antigen (HLA) matching criteria compared to bone marrow or peripheral blood stem cells, UCB enables patients lacking an HLA-matched donor to receive potentially curative SCT. METHODS: We retrospectively analyzed the efficacy and safety of UCB transplantation (UCBT) at our center. RESULTS: Between June 2009 and June 2015, 27 UCBT were performed in 25 patients. Reasons for the use of UCB were lack of adequate related or unrelated stem cell donor (n = 20) and graft failure after previous SCT (n = 7). Median time to neutrophil engraftment was 22 days. Four patients experienced primary graft failure. Thirteen patients developed acute graft-versus-host disease (GVHD), whereupon 6 subsequently also developed chronic GVHD. After a median follow-up time of 19 months, 9 patients relapsed and 12 patients died. Cause of death was relapse in 8 and transplant related events in 4 patients. Median overall survival and progression-free survival have not been reached yet. CONCLUSION: In our experience, UCBT is an alternative graft source for patients lacking a suitable related or unrelated donor and a feasible treatment option for patients experiencing graft failure after previous SCT. PMID- 26871561 TI - Decreasing Hepatitis C Virus Infection in Thailand in the Past Decade: Evidence from the 2014 National Survey. AB - Hepatitis C virus (HCV) infection affects >= 180 million individuals worldwide especially those living in developing countries. Recent advances in direct-acting therapeutics promise effective treatments for chronic HCV carriers, but only if the affected individuals are identified. Good treatment coverage therefore requires accurate epidemiological data on HCV infection. In 2014, we determined the current prevalence of HCV in Thailand to assess whether over the past decade the significant number of chronic carriers had changed. In total, 5964 serum samples from Thai residents between 6 months and 71 years of age were obtained from 7 provinces representing all 4 geographical regions of Thailand and screened for the anti-HCV antibody. Positive samples were further analyzed using RT-PCR, sequencing, and phylogenetic analysis to identify the prevailing HCV genotypes. We found that 56 (0.94%) samples tested positive for anti-HCV antibody (mean age = 36.6+/-17.6 years), while HCV RNA of the core and NS5B subgenomic regions was detected in 23 (41%) and 19 (34%) of the samples, respectively. The seropositive rates appeared to increase with age and peaked in individuals 41-50 years old. These results suggested that approximately 759,000 individuals are currently anti HCV-positive and that 357,000 individuals have viremic HCV infection. These numbers represent a significant decline in the prevalence of HCV infection. Interestingly, the frequency of genotype 6 variants increased from 8.9% to 34.8%, while the prevalence of genotype 1b declined from 27% to 13%. These most recent comprehensive estimates of HCV burden in Thailand are valuable towards evidence based treatment coverage for specific population groups, appropriate allocation of resources, and improvement in the national public health policy. PMID- 26871565 TI - A rare example of germ-line chromothripsis resulting in large genomic imbalance. AB - Chromothripsis is a recently described 'chromosome catastrophe' phenomenon in which multiple genomic rearrangements are generated in a single catastrophic event. Chromothripsis has most frequently been associated with cancer, but there have also been rare reports of chromothripsis in patients with developmental disorders and congenital anomalies. In contrast to the massive DNA loss that often accompanies chromothripsis in cancer, only minimal DNA loss has been reported in the majority of cases of chromothripsis that have occurred in the germ line. Presumably, this is because in most instances, large genomic losses would be lethal in utero. We report on a female patient with developmental delay and dysmorphism. G-banded chromosome analysis detected a subtle, interstitial deletion of chromosome 13 and a complex rearrangement of one X chromosome. Subsequent array comparative genomic hybridisation studies indicated nine deletions on the X chromosome ranging from 327 kb to 8 Mb in size. A 4.4 Mb deletion on chromosome 13 was also confirmed, compatible with the patient's clinical phenotype. We propose that this is a rare example of constitutional chromothripsis in association with relatively large genomic imbalances and that these have been tolerated in this case as they have occurred in a female on the X chromosome, which has undergone preferential X inactivation. PMID- 26871566 TI - Testicular Busulfan Injection in Mice to Prepare Recipients for Spermatogonial Stem Cell Transplantation Is Safe and Non-Toxic. AB - Current methods of administering busulfan to remove the endogenous germ cells cause hematopoietic toxicity, require special instruments and a narrow transplantation time. We use a direct testicular injection of busulfan method for preparing recipients for SSC transplantation. Male ICR mice (recipients) were divided into four groups, and two experimental groups were treated with a bilateral testicular injection of 4 or 6 mg/kg/side busulfan (n = 60 per concentration group). Mice received an intraperitoneal injection (i.p.) of 40 mg/kg busulfan (n = 60, positive control) and bilateral testicular injections of 50% DMSO (n = 60, negative control). Donor SSCs from RFP-transgenic C57BL/6J mice were introduced into the seminiferous tubules of each recipient testis via efferent duct injection on day 16-17 after busulfan treatment. Recipient mice mated with mature female ICR mice and the number of progeny was recorded. The index detected at day 14, 21, 28, 35 and 70 after busulfan treatment. Blood analysis shows that the toxicity of busulfan treated groups was much lower than i.p. injection groups. Fertility was restored in mice treated with busulfan and donor-derived offspring were obtained after SSC transplantation. Our study indicated that intratesticular injection busulfan for the preparation of recipients in mice is safe and feasible. PMID- 26871567 TI - Molecular Epidemiology and Transmission Dynamics of Recent and Long-Term HIV-1 Infections in Rural Western Kenya. AB - OBJECTIVE: To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naive participants in rural western Kenya. METHODS: Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression. RESULTS: Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age <=19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2-4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002. CONCLUSIONS: Recent HIV-1 infection was more frequent among 13-19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions. PMID- 26871568 TI - Degradation, Promoter Recruitment and Transactivation Mediated by the Extreme N Terminus of MHC Class II Transactivator CIITA Isoform III. AB - Multiple relationships between ubiquitin-proteasome mediated protein turnover and transcriptional activation have been well documented, but the underlying mechanisms are still poorly understood. One way to induce degradation is via ubiquitination of the N-terminal alpha-amino group of proteins. The major histocompatibility complex (MHC) class II transactivator CIITA is the master regulator of MHC class II gene expression and we found earlier that CIITA is a short-lived protein. Using stable and transient transfections of different CIITA constructs into HEK-293 and HeLa cell lines, we show here that the extreme N terminal end of CIITA isoform III induces both rapid degradation and transactivation. It is essential that this sequence resides at the N-terminal end of the protein since blocking of the N-terminal end with an epitope-tag stabilizes the protein and reduces transactivation potential. The first ten amino acids of CIITA isoform III act as a portable degron and transactivation sequence when transferred as N-terminal extension to truncated CIITA constructs and are also able to destabilize a heterologous protein. The same is observed with the N terminal ends of several known N-terminal ubiquitination substrates, such as Id2, Cdt1 and MyoD. Arginine and proline residues within the N-terminal ends contribute to rapid turnover. The N-terminal end of CIITA isoform III is responsible for efficient in vivo recruitment to the HLA-DRA promoter and increased interaction with components of the transcription machinery, such as TBP, p300, p400/Domino, the 19S ATPase S8, and the MHC-II promoter binding complex RFX. These experiments reveal a novel function of free N-terminal ends of proteins in degradation-dependent transcriptional activation. PMID- 26871569 TI - Mortality and Morbidity of Urban Road Traffic Crashes in Africa: Capture Recapture Estimates in Bamako, Mali, 2012. AB - BACKGROUND: Low- and middle-income countries are currently facing the massive public health challenge of road traffic injuries. The lack of effective surveillance systems hinders proper assessment of epidemiologic status and intervention priorities. The objective of our study was to estimate the mortality and morbidity attributable to road crashes in Bamako, Mali using the capture recapture method. METHODS: During the 1 January, 2012-31 April, 2012 period, we collected data on road traffic crashes from the road accident registers of the police forces of Bamako, Mali on the one hand, and from a register kept by health facilities in the same area. An automatic, then manual matching procedure was performed to find pairs of records related to the same crash victims. The number of victims and the number of fatalities were estimated by the capture-recapture method using the Chapman estimator. RESULTS: The health facility and the police registries included 3587 and 1432 records, respectively. The matching procedure identified 603 common records, 31 of which were fatalities. The annual incidence estimate for road victims was 1038 in 100 000 and the annual incidence estimate for road fatalities was 12 in 100 000. Victims from both sources were more likely to be male, in the 15-34 age group, and almost half of all injured road users and two in three fatalities were using motorized two-wheelers. One victim out of five was a pedestrian. CONCLUSION: Our estimates are in line with available literature data from low-income countries. While more cases were reported by health facilities than by police forces, we believe that an effective surveillance system should not be based solely on medical reports as much would be missing as regards the crash circumstances and characteristics. PMID- 26871570 TI - Mucorales-Specific T Cells in Patients with Hematologic Malignancies. AB - BACKGROUND: Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. METHODS AND FINDINGS: By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-gamma, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. CONCLUSIONS: Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM. PMID- 26871571 TI - IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response. AB - During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guerin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-gamma- and IL 17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice. PMID- 26871572 TI - Procrastination, Distress and Life Satisfaction across the Age Range - A German Representative Community Study. AB - Addressing the lack of population-based data the purpose of this representative study was to assess procrastination and its associations with distress and life satisfaction across the life span. A representative German community sample (1,350 women; 1,177 men) between the ages of 14 and 95 years was examined by the short form of the General Procrastination Scale (GPS-K; 1) and standardized scales of perceived stress, depression, anxiety, fatigue and life satisfaction. As hypothesized, procrastination was highest in the youngest cohort (14-29 years). Only in the youngest and most procrastinating cohort (aged 14 to 29 years), men procrastinated more than women. As we had further hypothesized, procrastination was consistently associated with higher stress, more depression, anxiety, fatigue and reduced satisfaction across life domains, especially regarding work and income. Associations were also found with lack of a partnership and unemployment. Findings are discussed with regard to potential developmental and cohort effects. While procrastination appears to be a pervasive indicator for maladjustment, longitudinal analyses in high-risk samples (e.g. late adolescence, unemployment) are needed to identify means and mechanisms of procrastinating. PMID- 26871573 TI - Regulation of alpha-Transducin and alpha-Gustducin Expression by a High Protein Diet in the Pig Gastrointestinal Tract. AB - BACKGROUND: The expression of taste receptors (TASRs) and their signalling molecules in the gastrointestinal (GI) epithelial cells, including enteroendocrine cells (EECs), suggests they participate in chemosensing mechanisms influencing GI physiology via the release of endocrine messengers. TASRs mediate gustatory signalling by interacting with different transducers, including alpha-gustducin (Galphagust) and alpha-transducin (Galphatran) G protein subunits. This study tested whether Galphatran and Galphagust immunoreactive (-IR) cells are affected by a short-term (3 days) and long-term (30 days) high protein (Hp) diet in the pig GI tract. RESULT: In the stomach, Galphagust and Galphatran-IR cells contained serotonin (5-HT) and ghrelin (GHR), while in the small and large intestine, Galphagust and Galphatran-IR colocalized with 5-HT-, cholecystokinin (CCK)- and peptide YY (PYY)-IR. There was a significant increase in the density of Galphatran-IR cells in the pyloric mucosa in both short- and long-term Hp diet groups (Hp3 and Hp30) vs. the control group (Ctr) (P<0.05), while the increase of Galphagust-IR cells in the pyloric mucosa was significant in Hp30 group vs. Ctr and vs. Hp3 (P<0.05); these cells included Galphatran / 5HT-IR and Galphatran / GHR-IR cells (P<0.05 and P<0.001 vs. Ctr, respectively) as well as Galphagust /5-HT-IR or Galphagust / GHR-IR cells (P<0.05 and P<0.01 vs. Ctr, respectively). In the small intestine, we recorded a significant increase in Galphatran-IR cells in the duodenal crypts and a significant increase of Galphagust-IR cells in the jejunal crypts in Hp3 group compared to HP30 (P<0.05). With regard to the number of Galphatran-Galphagust IR cells colocalized with CCK or 5-HT, there was only a significant increase of Galphatran / CCK-IR cells in Hp3 group compared to Ctr (P = 0.01). CONCLUSION: This study showed an upregulation of selected subpopulations of Galphagust / Galphatran-IR cells in distinct regions of the pig GI tract by short- and long term Hp diet lending support to TASR-mediated effects in metabolic homeostasis and satiety mechanisms. PMID- 26871574 TI - Phylogenomics Reveals Three Sources of Adaptive Variation during a Rapid Radiation. AB - Speciation events often occur in rapid bursts of diversification, but the ecological and genetic factors that promote these radiations are still much debated. Using whole transcriptomes from all 13 species in the ecologically and reproductively diverse wild tomato clade (Solanum sect. Lycopersicon), we infer the species phylogeny and patterns of genetic diversity in this group. Despite widespread phylogenetic discordance due to the sorting of ancestral variation, we date the origin of this radiation to approximately 2.5 million years ago and find evidence for at least three sources of adaptive genetic variation that fuel diversification. First, we detect introgression both historically between early branching lineages and recently between individual populations, at specific loci whose functions indicate likely adaptive benefits. Second, we find evidence of lineage-specific de novo evolution for many genes, including loci involved in the production of red fruit color. Finally, using a "PhyloGWAS" approach, we detect environment-specific sorting of ancestral variation among populations that come from different species but share common environmental conditions. Estimated across the whole clade, small but substantial and approximately equal fractions of the euchromatic portion of the genome are inferred to contribute to each of these three sources of adaptive genetic variation. These results indicate that multiple genetic sources can promote rapid diversification and speciation in response to new ecological opportunity, in agreement with our emerging phylogenomic understanding of the complexity of both ancient and recent species radiations. PMID- 26871577 TI - Correction: Deconstructing a Species-Complex: Geometric Morphometric and Molecular Analyses Define Species in the Western Rattlesnake (Crotalus viridis). PMID- 26871576 TI - Lipid Droplet Formation, Their Localization and Dynamics during Leishmania major Macrophage Infection. AB - Leishmania, the causative agent of vector-borne diseases, known as leishmaniases, is an obligate intracellular parasite within mammalian hosts. The outcome of infection depends largely on the activation status of macrophages, the first line of mammalian defense and the major target cells for parasite replication. Understanding the strategies developed by the parasite to circumvent macrophage defense mechanisms and to survive within those cells help defining novel therapeutic approaches for leishmaniasis. We previously showed the formation of lipid droplets (LDs) in L. major infected macrophages. Here, we provide novel insights on the origin of the formed LDs by determining their cellular distribution and to what extent these high-energy sources are directed to the proximity of Leishmania parasites. We show that the ability of L. major to trigger macrophage LD accumulation is independent of parasite viability and uptake and can also be observed in non-infected cells through paracrine stimuli suggesting that LD formation is from cellular origin. The accumulation of LDs is demonstrated using confocal microscopy and live-cell imagin in parasite-free cytoplasmic region of the host cell, but also promptly recruited to the proximity of Leishmania parasites. Indeed LDs are observed inside parasitophorous vacuole and in parasite cytoplasm suggesting that Leishmania parasites besides producing their own LDs, may take advantage of these high energy sources. Otherwise, these LDs may help cells defending against parasitic infection. These metabolic changes, rising as common features during the last years, occur in host cells infected by a large number of pathogens and seem to play an important role in pathogenesis. Understanding how Leishmania parasites and different pathogens exploit this LD accumulation will help us define the common mechanism used by these different pathogens to manipulate and/or take advantage of this high-energy source. PMID- 26871575 TI - HMGB1 Is Involved in IFN-alpha Production and TRAIL Expression by HIV-1-Exposed Plasmacytoid Dendritic Cells: Impact of the Crosstalk with NK Cells. AB - Plasmacytoid dendritic cells (pDCs) are innate sensors of viral infections and important mediators of antiviral innate immunity through their ability to produce large amounts of IFN-alpha. Moreover, Toll-like receptor 7 (TLR7) and 9 (TLR9) ligands, such as HIV and CpG respectively, turn pDCs into TRAIL-expressing killer pDCs able to lyse HIV-infected CD4+ T cells. NK cells can regulate antiviral immunity by modulating pDC functions, and pDC production of IFN-alpha as well as cell-cell contact is required to promote NK cell functions. Impaired pDC-NK cell crosstalk was reported in the setting of HIV-1 infection, but the impact of HIV-1 on TRAIL expression and innate antiviral immunity during this crosstalk is unknown. Here, we report that low concentrations of CCR5-tropic HIV-1Ba-L promote the release of pro-inflammatory cytokines such as IFN-alpha, TNF-alpha, IFN-gamma and IL-12, and CCR5-interacting chemokines (MIP-1alpha and MIP-1beta) in NK-pDCs co-cultures. At high HIV-1BaL concentrations, the addition of NK cells did not promote the release of these mediators, suggesting that once efficiently triggered by the virus, pDCs could not integrate new activating signals delivered by NK cells. However, high HIV-1BaL concentrations were required to trigger IFN alpha-mediated TRAIL expression at the surface of both pDCs and NK cells during their crosstalk. Interestingly, we identified the alarmin HMGB1, released at pDC NK cell synapse, as an essential trigger for the secretion of IFN-alpha and IFN related soluble mediators during the interplay of HIV-1 exposed pDCs with NK cells. Moreover, HMGB1 was found crucial for mTRAIL translocation to the plasma membrane of both pDCs and NK cells during their crosstalk following pDC exposure to HIV-1. Data from serum analyses of circulating HMGB1, HMGB1-specific antibodies, sTRAIL and IP-10 in a cohort of 67 HIV-1+ patients argue for the in vivo relevance of these observations. Altogether, these findings identify HMGB1 as a trigger for IFN-alpha-mediated TRAIL expression at the surface of pDCs and NK cells, and they suggest a novel mechanism of innate control of HIV-1 infection. PMID- 26871578 TI - DEPTOR promoter genetic variants and insulin resistance in obese children and adolescents. AB - BACKGROUND: Insulin resistance (IR) is one of the major metabolic complications of obesity in children and adolescents. DEP domain-containing mammalian target of rapamycin interacting protein (DEPTOR) is involved in downstream insulin signaling and DEPTOR's effects are regulated by its level of expression. OBJECTIVES: To analyze promoter region of DEPTOR for genetic variants associated with altered IR in obese children and adolescents. SUBJECTS AND METHODS: IR was determined in 322 normoglycemic obese subjects [173 females, 149 males; mean age 13.3 +/- 3.5 yr, mean BMI-SDS 2.85 +/- 0.83, HbA1C 5.2 +/- 0.2% (33 +/- 2.5 mmol/mol)] using homeostatic model assessment - insulin resistance [HOMA-IR (>2 prepubertal and >3 pubertal)] and whole body insulin sensitivity index [WBISI (<6.5 prepubertal and <4.5 pubertal)]. Genetic variants, determined by high resolution melting analysis, were confirmed by Sanger sequencing, whereas population allele distribution was determined by TaqMan genotyping probes. RESULTS: Genetic variant c.-143T>C (rs7840156) was associated with a significant 2-fold decreased risk to present with IR, determined by HOMA-IR [odds ratio (OR) = 0.614, 95% confidence interval (CI) = 0.435-0.867, p = 0.0057) and WBISI (OR = 0.582, 95% CI = 0.414-0.817, p = 0.0018). The CC genotype had lower mean HOMA-IR value (2.47 +/- 0.44 vs. 3.04 +/- 0.14, p = 0.0177) and higher mean WBISI value (7.00 +/- 0.71 vs. 5.27 +/- 0.33, p = 0.0235) than TT genotype. Variant c.-143T>C was located in evolutionary highly conserved region in DEPTOR promoter region. CONCLUSION: Presented results on association between insulin sensitivity and genetic variants in DEPTOR gene suggest DEPTOR and mammalian target of rapamycin signaling pathway to be potential target for future research and pharmacological interventions. PMID- 26871579 TI - Use of Selective Cyclooxygenase-2 Inhibitors, Other Analgesics, and Risk of Glioma. AB - BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors are analgesic, antipyretic, and anti-inflammatory drugs. They have been found to inhibit the development of glioma in laboratory investigations. Whether these drugs reduce the risk of glioma incidence in humans is unknown. METHODS: We conducted a matched case-control analysis using the U.K.-based Clinical Practice Research Datalink (CPRD). We identified 2,469 cases matched to 24,690 controls on age, sex, calendar time, general practice, and number of years of active history in the CPRD prior to the index date. We conducted conditional logistic regression analyses to determine relative risks, estimated as odds ratios (ORs) with 95% confidence intervals (CIs) of glioma in relation to use of selective COX-2 inhibitors, adjusted for several confounding variables. RESULTS: Use of selective COX-2 inhibitors was unrelated to risk of glioma (adjusted OR for 1-9 versus 0 prescriptions = 1.02; 95% CI = 0.92-1.13, 10-29 versus 0 prescriptions = 1.01; 95% CI = 0.80-1.28, >=30 versus 0 prescriptions = 1.16; 95% CI = 0.86-1.55). Trends for increasing numbers of prescriptions for other non-steroidal anti inflammatory drugs (NSAIDs), and non-NSAID analgesics were also not associated with glioma risk. CONCLUSION: Further epidemiologic studies are needed to confirm the null relation of use of selective COX-2 inhibitors to glioma risk and to explain the discrepancy between laboratory investigations and our observational study. IMPACT: Use of selective COX-2 inhibitors is unrelated to glioma risk. PMID- 26871580 TI - An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection. AB - Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub communities, with each community containing a consortium of organisms that co occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism. PMID- 26871581 TI - Systems Biology Approaches for the Prediction of Possible Role of Chlamydia pneumoniae Proteins in the Etiology of Lung Cancer. AB - Accumulating evidence has recently supported the association of bacterial infection with the growth and development of cancers, particularly in organs that are constantly exposed to bacteria such as the lungs, colon, cervical cancer etc. Our in silico study on the proteome of Chlamydia pneumoniae suggests an unprecedented idea of the etiology of lung cancer and have revealed that the infection of C. pneumoniae is associated with lung cancer development and growth. It is reasonable to assume that C. pneumoniae transports its proteins within host intracellular organelles during infection, where they may work with host-cell proteome. The current study was performed for the prediction of nuclear targeting protein of C. pneumoniae in the host cell using bioinformatics predictors including ExPASy pI/Mw tool, nuclear localization signal (NLS) mapper, balanced sub cellular localization predictor (BaCeILo), and Hum-mPLoc 2.0. We predicted 47/1112 nuclear-targeting proteins of C. pneumoniae connected with several possible alterations in host replication and transcription during intracellular infection. These nuclear-targeting proteins may direct to competitive interactions of host and C. pneumoniae proteins with the availability of same substrate and may be involved as etiological agents in the growth and development of lung cancer. These novel findings are expected to access in better understanding of lung cancer etiology and identifying molecular targets for therapy. PMID- 26871582 TI - A different kind of case report: I. PMID- 26871583 TI - Lengthened Cutaneous Silent Period in Fibromyalgia Suggesting Central Sensitization as a Pathogenesis. AB - The pathogenesis of fibromyalgia (FM) has not been clearly elucidated, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main mechanism. The cutaneous silent period (CSP), which is a spinal reflex mediated by A-delta cutaneous afferents, is useful for the evaluation of sensorimotor integration at the spinal and supraspinal levels. To understand the pathophysiology of FM, we compared CSP patterns between patients with FM and normal healthy subjects. Twenty-four patients with FM diagnosed in accordance with the 1990 American College of Rheumatology classification system and 24 age- and sex-matched healthy volunteers were recruited. The CSP was measured from the abductor pollicis brevis muscle. Demographic data, number of tender points, and visual analog scale and FM impact questionnaire scores were collected. The measured CSP and clinical parameters of the patient and control groups were compared. In addition, possible correlations between the CSP parameters and the other clinical characteristics were analyzed. Mean CSP latencies did not differ between patients (55.50 +/- 10.97 ms) and healthy controls (60.23 +/- 11.87 ms; p = 0.158), although the mean CSP duration was significantly longer in patients (73.75 +/- 15.67 ms) than in controls (63.50 +/- 14.05 ms; p = 0.021). CSP variables did not correlate with any clinical variables. The significantly longer CSP duration in FM patients suggests central dysregulation at the spinal and supraspinal levels, rather than peripheral small fiber dysfunction. PMID- 26871584 TI - Routine Primary Prophylaxis for Febrile Neutropenia with Biosimilar Granulocyte Colony-Stimulating Factor (Nivestim) or Pegfilgrastim Is Cost Effective in Non Hodgkin Lymphoma Patients undergoing Curative-Intent R-CHOP Chemotherapy. AB - OBJECTIVE: This study aims to compare the cost-effectiveness of various strategies of myeloid growth factor prophylaxis for reducing the risk of febrile neutropenia (FN) in patients with non-Hodgkin lymphoma in Singapore who are undergoing R-CHOP chemotherapy with curative intent. METHODS: A Markov model was created to compare seven prophylaxis strategies: 1) primary prophylaxis (PP) with nivestim (biosimilar filgrastim) throughout all cycles of chemotherapy; 2) PP with nivestim during the first two cycles of chemotherapy; 3) secondary prophylaxis (SP) with nivestim; 4) PP with pegfilgrastim throughout all cycles of chemotherapy; 5) PP with pegfilgrastim during the first two cycles of chemotherapy; 6) SP with pegfilgrastim; and 7) no prophylaxis (NP). The perspective of a hospital was taken and cost-effectiveness was expressed as the cost per episode of FN avoided over six cycles of chemotherapy. A probabilistic sensitivity analysis was conducted. RESULTS: Strategies 3, 6, and 7 were dominated in the base case analysis by strategy 5. The costs associated with strategies 2, 5, 1, and 4 were US$3,813, US$4,056, US$4,545, and US$5,331, respectively. The incremental cost-effectiveness ratios for strategy 5 vs. strategy 2, strategy 1 vs. strategy 5, and strategy 4 vs. strategy 1 were US$13,532, US$22,565, and US$30,452, respectively, per episode of FN avoided. Strategy 2 has the highest probability to be cost-effective (ranged from 48% to 60%) when the willingness to pay (WTP) threshold is lower than US$10,000 per FN episode prevented. CONCLUSION: In Singapore, routine PP with granulocyte colony stimulating factor (nivestim or pegfilgrastim) is cost-effective for reducing the risk of FN in patients receiving R-CHOP. PMID- 26871585 TI - Reduced thermal threshold in patients with Temporomandibular Disorders. AB - BACKGROUND: Many studies have demonstrated the presence of somatosensory modulation changes at different sites in patients with temporomandibular disorders (TMDs) using different modalities. However, the neck area, a well-know condition related to TMD, remains unexplored. OBJECTIVE: To assess the thermal pain threshold in patients with TMD and controls at cephalic and extra-cephalic areas, including the neck. METHODS: Twenty female patients with TMDs diagnosed by the Research Diagnostic Criteria for TMD (RDC/TMD) and twenty age-matched controls underwent a first interview about neck pain and disability (NDI questionnaire). A blinded evaluator assessed the thermal pain threshold for cold (CPT) and heat (HPT) stimuli in accordance with an ascending method of limits of the Quantitative Sensory Testing at the following sites: periorbital, masseter, cervical posterior and ventral forearm. The groups were compared using a t-test with alpha = 5%. RESULTS: Patients with TMDs reported pain at higher temperature for cold stimuli in all sites (P < 0.05) and at lower temperature for heat stimuli in the right periorbital site (P < 0.05) than controls. Pain and disability due tothis symptom were reported more often in the TMD group (P < 0.05). CONCLUSION: Patients with TMD have pain modulation changes in the neck area as well, especially for cold stimuli, associated with higher disability and a higher report of neck pain than controls. These findings reinforce the evidence regarding the relationship between TMDs and neck pain. PMID- 26871587 TI - The Perceived Likelihood of Outcome of Critical Care Patients and Its Impact on Triage Decisions: A Case-Based Survey of Intensivists and Internists in a Canadian, Quaternary Care Hospital Network. AB - INTRODUCTION: There is high variability amongst physicians' assessments of appropriate ICU admissions, which may be based on potential assessments of benefit. We aimed to examine whether opinions over benefit of ICU admissions of critically ill medical inpatients differed based on physician specialty, namely intensivists and internists. MATERIALS AND METHODS: We carried out an anonymous, web-based questionnaire survey containing 5 typical ICU cases to all ICU physicians regardless of their base specialty as well as to all internists in 3 large teaching hospitals. For each case, we asked the participants to determine if the patient was an appropriate ICU admission and to assess different parameters (e.g. baseline function, likelihood of survival to ICU discharge, etc.). Agreement was measured using kappa values. RESULTS: 21 intensivists and 22 internists filled out the survey (response rate = 87.5% and 35% respectively). Predictions of likelihood of survival to ICU admission, hospital discharge and return to baseline were not significantly different between the two groups. However, agreement between individuals within each group was only slight to fair (kappa range = 0.09-0.22). There was no statistically significant difference in predicting ICU survival and prediction of survival to hospital discharge between both groups. The accuracy with which physicians predicted actual outcomes ranged between 35% and 100% and did not significantly differ between the two groups. A greater proportion of internists favoured non resuscitative measures (24.6% of intensivists and 46.9% internists [p = 0.002]). CONCLUSION: In a case-based survey, physician specialty base did not affect assessments of ICU admission benefit or accuracy in outcome prediction, but resulted in a statistically significant difference in level of care assignments. Of note, significant disagreement amongst individuals in each group was found. PMID- 26871586 TI - Carriage of lambda Latent Virus Is Costly for Its Bacterial Host due to Frequent Reactivation in Monoxenic Mouse Intestine. AB - Temperate phages, the bacterial viruses able to enter in a dormant prophage state in bacterial genomes, are present in the majority of bacterial strains for which the genome sequence is available. Although these prophages are generally considered to increase their hosts' fitness by bringing beneficial genes, studies demonstrating such effects in ecologically relevant environments are relatively limited to few bacterial species. Here, we investigated the impact of prophage carriage in the gastrointestinal tract of monoxenic mice. Combined with mathematical modelling, these experimental results provided a quantitative estimation of key parameters governing phage-bacteria interactions within this model ecosystem. We used wild-type and mutant strains of the best known host/phage pair, Escherichia coli and phage lambda. Unexpectedly, lambda prophage caused a significant fitness cost for its carrier, due to an induction rate 50 fold higher than in vitro, with 1 to 2% of the prophage being induced. However, when prophage carriers were in competition with isogenic phage susceptible bacteria, the prophage indirectly benefited its carrier by killing competitors: infection of susceptible bacteria led to phage lytic development in about 80% of cases. The remaining infected bacteria were lysogenized, resulting overall in the rapid lysogenization of the susceptible lineage. Moreover, our setup enabled to demonstrate that rare events of phage gene capture by homologous recombination occurred in the intestine of monoxenic mice. To our knowledge, this study constitutes the first quantitative characterization of temperate phage-bacteria interactions in a simplified gut environment. The high prophage induction rate detected reveals DNA damage-mediated SOS response in monoxenic mouse intestine. We propose that the mammalian gut, the most densely populated bacterial ecosystem on earth, might foster bacterial evolution through high temperate phage activity. PMID- 26871588 TI - Vitamin D deficiency is associated with prediabetes in obese Swedish children. AB - AIM: Low vitamin D levels have been associated with obesity and living in areas that lack sunshine, such as northern Europe. The aim of this study was to investigate the vitamin D status of a group of obese children in Sweden and to investigate the associations between vitamin D status and markers of glucose metabolism and metabolic risk markers. METHODS: This was a prospective cross sectional study of 202 obese children between 4.5 and 17.9 years of age who had been referred to the National Childhood Obesity Centre at Karolinska University Hospital, Stockholm. We examined age, gender, 25-hydroxyvitamin D (25(OH)D), f glucose, f-insulin and metabolic risk markers. Vitamin D deficiency was defined as less than 30 25(OH)D nmol/L. Children with and without a vitamin D deficiency were compared. RESULTS: Just over a third (33.2%) of our study population had vitamin D levels <30 nmol/L 25(OH)D. A significant interaction effect was found between age and 25(OH)D. An association was also found between low 25(OH)D levels and impaired fasting glycaemia (IFG) independent of age and season. CONCLUSION: Low vitamin D levels were common among obese adolescents living in Sweden and were strongly associated with age and associated with a higher risk of IFG. PMID- 26871589 TI - Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets. AB - OBJECTIVE: To design an experimental pediatric animal model of acute kidney injury induced by cisplatin. METHODS: Prospective comparative observational animal study in two different phases. Acute kidney injury was induced using three different doses of cisplatin (2, 3 and 5 mg/kg). The development of nephrotoxicity was assessed 2 to 4 days after cisplatin administration by estimating biochemical parameters, diuresis and renal morphology. Analytical values and renal morphology were compared between 15 piglets treated with cisplatin 3 mg/kg and 15 control piglets in the second phase of the study. RESULTS: 41 piglets were studied. The dose of 3 mg/kg administered 48 hours before the experience induced a significant increase in serum creatinine and urea without an increase in potassium levels. Piglets treated with cisplatin 3 mg/kg had significantly higher values of creatinine, urea, phosphate and amylase, less diuresis and lower values of potassium, sodium and bicarbonate than control piglets. Histological findings showed evidence of a dose-dependent increase in renal damage. CONCLUSIONS: a dose of 3 mg/kg of cisplatin induces a significant alteration in renal function 48 hours after its administration, so it can be used as a pediatric animal model of non-oliguric acute kidney injury. PMID- 26871590 TI - Differential heart rate responses to social and monetary reinforcement in women with obesity. AB - Obesity is often accompanied by weight stigmatization; subsequently, individuals with obesity frequently face social rejection. It has been shown that recurrent negative social experiences can alter the perception of social cues. However, the way individuals with obesity process social stimuli is not well understood. This study aims to investigate obesity-related alterations in social compared to nonsocial information processing. Women with obesity (n = 14) and without obesity (n = 14) participated in a social and a monetary incentive delay task in which they anticipated and received positive, negative, and neutral outcomes in the form of faces or money. During the experiment, phasic heart rate changes and reaction times were measured. Women with obesity, compared to lean women, exhibited a stronger differentiation during the anticipation of monetary and social reinforcement, showing slower reaction times to social cues compared to monetary cues. During the outcome processing phase, women with obesity relative to controls demonstrated diminished heart rate responses particularly to negative social outcomes. Interestingly, differences in cardiac responses in participants with obesity were moderated by weight-related teasing experiences. In women with obesity, a higher BMI was associated with blunted cardiac responses to social cues relative to monetary cues only if they reported more emotional pain after weight-related teasing. Our results contribute to a better understanding of social information processing in obesity and give first evidence for the role of negative social experiences in reinforcement processing. PMID- 26871592 TI - Fast, Accurate Simulation of Polaron Dynamics and Multidimensional Spectroscopy by Multiple Davydov Trial States. AB - By employing the Dirac-Frenkel time-dependent variational principle, we study the dynamical properties of the Holstein molecular crystal model with diagonal and off-diagonal exciton-phonon coupling. A linear combination of the Davydov D1 (D2) ansatz, referred to as the "multi-D1 ansatz" ("multi-D2 ansatz"), is used as the trial state with enhanced accuracy but without sacrificing efficiency. The time evolution of the exciton probability is found to be in perfect agreement with that of the hierarchy equations of motion, demonstrating the promise the multiple Davydov trial states hold as an efficient, robust description of dynamics of complex quantum systems. In addition to the linear absorption spectra computed for both diagonal and off-diagonal cases, for the first time, 2D spectra have been calculated for systems with off-diagonal exciton-phonon coupling by employing the multiple D2 ansatz to compute the nonlinear response function, testifying to the great potential of the multiple D2 ansatz for fast, accurate implementation of multidimensional spectroscopy. It is found that the signal exhibits a single peak for weak off-diagonal coupling, while a vibronic multipeak structure appears for strong off-diagonal coupling. PMID- 26871591 TI - Exome Sequencing in Classic Hairy Cell Leukaemia Reveals Widespread Variation in Acquired Somatic Mutations between Individual Tumours Apart from the Signature BRAF V(600)E Lesion. AB - In classic Hairy cell leukaemia (HCLc), a single case has thus far been interrogated by whole exome sequencing (WES) in a treatment naive patient, in which BRAF V(600)E was identified as an acquired somatic mutation and confirmed as occurring near-universally in this form of disease by conventional PCR-based cohort screens. It left open however the question whether other genome-wide mutations may also commonly occur at high frequency in presentation HCLc disease. To address this, we have carried out WES of 5 such typical HCLc cases, using highly purified splenic tumour cells paired with autologous T cells for germline. Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these HCLc exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease. These data then place mutant BRAF at the centre of the neoplastic drive in HCLc. A comparison of our exome data with emerging genetic findings in HCL indicates that additional somatic mutations may however occur recurrently in smaller subsets of disease. As mutant BRAF alone is insufficient to drive malignant transformation in other histological cancers, it suggests that individual tumours utilise largely differing patterns of genetic somatic mutations to coalesce with BRAF V(600)E to drive pathogenesis of malignant HCLc disease. PMID- 26871593 TI - Colonic content in health and its relation to functional gut symptoms. AB - BACKGROUND: Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. METHODS: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. KEY RESULTS: In healthy subjects both gaseous (87 +/- 24 mL) and non-gaseous colonic content (714 +/- 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 +/- 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. CONCLUSIONS & INFERENCES: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved. PMID- 26871594 TI - Laying a Community-Based Foundation for Data-Driven Semantic Standards in Environmental Health Sciences. AB - BACKGROUND: Despite increasing availability of environmental health science (EHS) data, development, and implementation of relevant semantic standards, such as ontologies or hierarchical vocabularies, has lagged. Consequently, integration and analysis of information needed to better model environmental influences on human health remains a significant challenge. OBJECTIVES: We aimed to identify a committed community and mechanisms needed to develop EHS semantic standards that will advance understanding about the impacts of environmental exposures on human disease. METHODS: The National Institute of Environmental Health Sciences sponsored the "Workshop for the Development of a Framework for Environmental Health Science Language" hosted at North Carolina State University on 15-16 September 2014. Through the assembly of data generators, users, publishers, and funders, we aimed to develop a foundation for enabling the development of community-based and data-driven standards that will ultimately improve standardization, sharing, and interoperability of EHS information. DISCUSSION: Creating and maintaining an EHS common language is a continuous and iterative process, requiring community building around research interests and needs, enabling integration and reuse of existing data, and providing a low barrier of access for researchers needing to use or extend such a resource. CONCLUSIONS: Recommendations included developing a community-supported web-based toolkit that would enable a) collaborative development of EHS research questions and use cases, b) construction of user-friendly tools for searching and extending existing semantic resources, c) education and guidance about standards and their implementation, and d) creation of a plan for governance and sustainability. CITATION: Mattingly CJ, Boyles R, Lawler CP, Haugen AC, Dearry A, Haendel M. 2016. Laying a community-based foundation for data-driven semantic standards in environmental health sciences. Environ Health Perspect 124:1136-1140; http://dx.doi.org/10.1289/ehp.1510438. PMID- 26871596 TI - Exploring the multifaceted nature of the common lymphoid progenitor compartment. AB - While the common lymphoid progenitor compartment was originally thought to be a rather homogenous cell population, it has become increasingly clear that this compartment is highly heterogeneous both with regard to phenotypic and functional features. The exploration of this cellular complexity has generated novel molecular insights into regulatory events in lymphoid lineage restriction and provided support for the idea that multiple lineage restriction events occur at this developmental stage. Furthermore, the identification of multiple lineage restricted progenitors with mixed lineage potential challenges a strictly hierarchical model for lymphoid development. Instead we propose a model based on competence windows during which cell fates are established through the action of lineage determining factors. PMID- 26871595 TI - The development of adult innate lymphoid cells. AB - Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID- 26871597 TI - Regulation of T cell signaling and autoimmunity by RNA-binding proteins. AB - Post-transcriptional gene regulation by RNA-binding proteins controls mRNA half life and efficiency of translation. Recently, the RNA-binding proteins Roquin and Regnase-1 have been shown to play pivotal roles in T lymphocytes by preventing inflammatory and autoimmune disease. These factors share an overlapping set of target mRNAs and are both regulated by proteolytic cleavage through the paracaspase MALT1. This review discusses the mouse models of inactivation or deregulation and how these trans-acting factors recognize target mRNAs. Based on different affinities of cis-elements in target mRNAs and regulation of the trans acting factors, we propose the following model: Increasing TCR signal strength will gradually inactivate Roquin and Regnase-1 causing differential target mRNA derepression that specifies cell fate decisions and effector functions of T cells. PMID- 26871598 TI - Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer. AB - BACKGROUND: Previous preclinical and clinical studies have shown that levels of tumor-infiltrating lymphocytes (TILs) significantly correlated with prognosis in non-small cell lung cancer (NSCLC), and survival after therapy; however, this finding remains controversial. We performed a meta-analysis, to evaluate, systematically, the clinical utilization of TIL subtypes in patients with NSCLC. METHODS: The PubMed, ISI Web of Science, EMBASE, and Cochrane Library databases were searched to identify relevant studies. We pooled estimates of treatment effects, and hazards were summarized using random or fixed effects models to evaluate survival outcomes. RESULTS: A total of 24 relevant studies involving 7,006 patients were eligible. The median percentage of lymph node positivity was 45.7% (95% confidence interval [CI], 37.1-56.4%). Pooled analysis shows that high levels of CD8+ TILs had a good prognostic effect on survival with a hazard ratio (HR) of 0.91 (P = 0.013) for death and 0.74 (P = 0.001) for recurrence, as did high levels of CD3+ and CD4+ TILs, with HRs of 0.77 (P = 0.009) and 0.78 (P = 0.005) for death, respectively. By contrast, high levels of FoxP3+ regulatory TILs had a worse prognostic effect for overall and recurrence-free survival, with HRs of 1.69 (P = 0.042) and 1.79 (P = 0.001), respectively. No individual study affected the results, and no publication bias was found. CONCLUSIONS: Our findings support the hypothesis that TILs could be a prognostic marker in NSCLC. High-quality randomized studies are needed to verify statistically the effect of TILs on prognosis in future research. PMID- 26871599 TI - Monoamine oxidase A (MAO A) inhibitors decrease glioma progression. AB - Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI 148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-alone drugs or as combination therapy with low dose TMZ for drug resistant gliomas. NMI can also be used as a non-invasive imaging tool. Thus has a dual function for both therapy and diagnosis. PMID- 26871600 TI - A propensity score matching analysis of survival following segmentectomy or wedge resection in early-stage lung invasive adenocarcinoma or squamous cell carcinoma. AB - PURPOSE: To compare the survival outcomes following segmentectomy or wedge resection in early-stage lung cancer. METHODS: A total of 5880 patients with invasive lung adenocarcinoma or squamous cell carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database were included in this study, of which 1156 received segmentectomy. Baseline characteristics were balanced using propensity score methods. Cox regression analysis was used to compare overall survival (OS) and lung cancer-specific survival (LCSS) following segmentectomy or wedge resection after matching patients based on propensity scores. RESULTS: Overall, patients undergoing segmentectomy and wedge resection had no significant different OS and LCSS both in the invasive adenocarcinoma group and the squamous cell carcinoma group. Segmentectomy was associated with improved OS (hazard ratio = 0.626, 95% confidence interval: 0.457-0.858, P = 0.004) and LCSS (hazard ratio = 0.643, 95% CI: 0.440-0.939, P = 0.022) in invasive adenocarcinoma patients <= 65 years old. In patients with <= 2 cm invasive adenocarcinoma, segmentectomy was associated with significantly better OS (hazard ratio = 0.811, 95% confidence interval: 0.666-0.988, P = 0.038). CONCLUSIONS: Survival following segmentectomy or wedge resection was generally equivalent in lung invasive adenocarcinoma and squamous cell carcinoma. However, invasive adenocarcinoma patients who were <= 65 years or had tumors <= 2 cm in size may have improved survival outcomes after segmentectomy. PMID- 26871601 TI - Acquisition of tumorigenic potential and enhancement of angiogenesis in pulmonary stem/progenitor cells through Oct-4 hyperexpression. AB - Cancer stem cells, also known as cancer initiating cells (CICs), are considered to be responsible for tumor growth and chemoresistance. Different hypotheses have been proposed to explain the origin of CICs, including mutations in adult stem/progenitor cells or the acquisition of stem-like characteristics in differentiated cells; however, studies have yielded conflicting identification for CICs and have little information for the origin to generate CICs. Part of the difficulty in identifying CICs may stem from the fact that the CICs studied have been largely derived from cancer cell lines or well-developed tumors. In previous studies, we have reported the enrichment of mouse pulmonary stem/progenitor cells (mPSCs) by using serum-free primary selection culture followed by FACS isolation using the coxsackievirus/adenovirus receptor (CAR) as the positive selection marker. Here, we demonstrated that overexpression of the pluripotent transcription factor Oct-4 is sufficient to induce CAR+/mPSCs transformation, which we name CAR+/mPSCsOct-4_hi. These transformed cells possess cancer initiating and chemoresistance potential, as well as exhibiting remarkable expression of certain proangiogenic factors, including angiopoietins (ANGs) and VEGF, and enhanced angiogenic potential. Moreover, CAR+/mPSCsOct-4_hi actively participated in tumor blood vessel formation and triggered a novel angiogenic mechanism, the angiopoietins/Tie2 signaling pathway. These study provide critical evidence supporting the possible origin to generate CICs, and help elucidate the pathways responsible for CICs-mediated blood vessel formation. PMID- 26871603 TI - Phonocardiogram signal compression using sound repetition and vector quantization. AB - BACKGROUND: A phonocardiogram (PCG) signal can be recorded for long-term heart monitoring. A huge amount of data is produced if the time of a recording is as long as days or weeks. It is necessary to compress the PCG signal to reduce storage space in a record and play system. In another situation, the PCG signal is transmitted to a remote health care center for automatic analysis in telemedicine. Compression of the PCG signal in that situation is necessary as a means for reducing the amount of data to be transmitted. Since heart beats are of a cyclical nature, compression can make use of the similarities in adjacent cycles by eliminating repetitive elements as redundant. This study proposes a new compression method that takes advantage of these repetitions. METHODS: Data compression proceeds in two stages, a training stage followed by the compression as such. In the training stage, a section of the PCG signal is selected and its sounds and murmurs (if any) decomposed into time-frequency components. Basic components are extracted from these by clustering and collected to form a dictionary that allows the generative reconstruction and retrieval of any heart sound or murmur. In the compression stage, the heart sounds and murmurs are reconstructed from the basic components stored in the dictionary. Compression is made possible because only the times of occurrence and the dictionary indices of the basic components need to be stored, which greatly reduces the number of bits required to represent heart sounds and murmurs. The residual that cannot be reconstructed in this manner appears as a random sequence and is further compressed by vector quantization. What we propose are quick search parameters for this vector quantization. RESULTS: For normal PCG signals the compression ratio ranges from 20 to 149, for signals with median murmurs it ranges from 14 to 35, and for those with heavy murmurs, from 8 to 20, subject to a degree of distortion of ~5% (in percent root-mean-square difference) and a sampling frequency of 4kHz. DISCUSSION: We discuss the selection of the training signal and the contribution of vector quantization. Performance comparisons between the method proposed in this study and existing methods are conducted by computer simulations. CONCLUSIONS: When recording and compressing cyclical sounds, any repetitive components can be removed as redundant. The redundancies in the residual can be reduced by vector quantization. The method proposed in this study achieves a better performance than existing methods. PMID- 26871602 TI - The mannose receptor LY75 (DEC205/CD205) modulates cellular phenotype and metastatic potential of ovarian cancer cells. AB - The molecular basis of epithelial ovarian cancer (EOC) dissemination is still poorly understood. Previously, we identified the mannose receptor LY75 gene as hypomethylated in high-grade (HG) serous EOC tumors, compared to normal ovarian tissues. LY75 represents endocytic receptor expressed on dendritic cells and so far, has been primarily studied for its role in antigen processing and presentation. Here we demonstrate that LY75 is overexpressed in advanced EOC and that LY75 suppression induces mesenchymal-to-epithelial transition (MET) in EOC cell lines with mesenchymal morphology (SKOV3 and TOV112), accompanied by reduction of their migratory and invasive capacity in vitro and enhanced tumor cell colonization and metastatic growth in vivo. LY75 knockdown in SKOV3 cells also resulted in predominant upregulation of functional pathways implicated in cell proliferation and metabolism, while pathways associated with cell signaling and adhesion, complement activation and immune response were mostly suppressed. Moreover, LY75 suppression had an opposite effect on EOC cell lines with epithelial phenotype (A2780s and OV2008), by directing epithelial-to-mesenchymal transition (EMT) associated with reduced capacity for in vivo EOC cell colonization, as similar/identical signaling pathways were reversely regulated, when compared to mesenchymal LY75 knockdown EOC cells.To our knowledge, this is the first report of a gene displaying such pleiotropic effects in sustaining the cellular phenotype of EOC cells and points to novel functions of this receptor in modulating EOC dissemination. Our data also support previous findings regarding the superior capacity of epithelial cancer cells in metastatic colonization of distant sites, compared to cancer cells with mesenchymal-like morphology. PMID- 26871604 TI - Endovascular thrombectomy in acute ischemic stroke: a major breakthrough and a big challenge for Brazil. PMID- 26871605 TI - Testing for haptic perception. PMID- 26871606 TI - Correction to "Chiral Conjugated Corrals". PMID- 26871607 TI - Single Particle Deformation and Analysis of Silica-Coated Gold Nanorods before and after Femtosecond Laser Pulse Excitation. AB - We performed single particle deformation experiments on silica-coated gold nanorods under femtosecond (fs) illumination. Changes in the particle shape were analyzed by electron microscopy and associated changes in the plasmon resonance by electron energy loss spectroscopy. Silica-coated rods were found to be more stable compared to uncoated rods but could still be deformed via an intermediate bullet-like shape for silica shell thicknesses of 14 nm. Changes in the size ratio of the rods after fs-illumination resulted in blue-shifting of the longitudinal plasmon resonances. Two-dimensional spatial mapping of the plasmon resonances revealed that the flat side of the bullet-like particles showed a less pronounced longitudinal plasmonic electric field enhancement. These findings were confirmed by finite-difference time-domain (FDTD) simulations. Furthermore, at higher laser fluences size reduction of the particles was found as well as for particles that were not completely deformed yet. PMID- 26871608 TI - Stereochemical Course of the Reaction Catalyzed by RimO, a Radical SAM Methylthiotransferase. AB - RimO is a member of the growing radical S-adenosylmethionine (SAM) superfamily of enzymes, which use a reduced [4Fe-4S] cluster to effect reductive cleavage of the 5' C-S bond of SAM to form a 5'-deoxyadenosyl 5'-radical (5'-dA(*)) intermediate. RimO uses this potent oxidant to catalyze the attachment of a methylthio group ( SCH3) to C3 of aspartate 89 of protein S12, one of 21 proteins that compose the 30S subunit of the bacterial ribosome. However, the exact mechanism by which this transformation takes place has remained elusive. Herein, we describe the stereochemical course of the RimO reaction. Using peptide mimics of the S12 protein bearing deuterium at the 3 pro-R or 3 pro-S positions of the target aspartyl residue, we show that RimO from Bacteroides thetaiotaomicron (Bt) catalyzes abstraction of the pro-S hydrogen atom, as evidenced by the transfer of deuterium into 5'-deoxyadenosine (5'-dAH). The observed kinetic isotope effect on H atom versus D atom abstraction is ~1.9, suggesting that this step is at least partially rate determining. We also demonstrate that Bt RimO can utilize the flavodoxin/flavodoxin oxidoreductase/NADPH reducing system from Escherichia coli as a source of requisite electrons. Use of this in vivo reducing system decreases, but does not eliminate, formation of 5'-dAH in excess of methylthiolated product. PMID- 26871609 TI - Chiral all-organic nitroxide biradical liquid crystals showing remarkably large positive magneto-LC effects. AB - The liquid crystalline chiral nitroxide biradical (S,S,S,S)-3 synthesized has shown much larger 'positive magneto-LC effects' in the chiral nematic (N*) phase than the monoradical (S,S)-1. PMID- 26871611 TI - High-performance piezoelectric nanogenerators for self-powered nanosystems: quantitative standards and figures of merit. AB - Harvesting energies from the atmosphere cost-effectively is critical for both addressing worldwide long-term energy needs at the macro-scale, and achieving the sustainable maintenance-free operation of nanodevices at the micro-scale (Wang and Wu 2012 Angew. Chem. Int. Ed. 51 11700-21). Piezoelectric nanogenerator (NG) technology has demonstrated its great application potential in harvesting the ubiquitous and abundant mechanical energy. Despite of the progress made in this rapidly-advancing field, a fundamental understanding and common standard for consistently quantifying and evaluating the performance of the various types of piezoelectric NGs is still lacking. In their recent study Crossley and Kar Narayan (2015 Nanotechnology 26 344001), systematically investigated dynamical properties of piezoelectric NGs by taking into account the effect of driving mechanism and load frequency on NG performance. They further defined the NGs' figures of merit as energy harvested normalized by applied strain or stress for NGs under strain-driven or stress-driven conditions, which are commonly seen in the vibrational energy harvesting. This work provides new insight and a feasible approach for consistently evaluating piezoelectric nanomaterials and NG devices, which is important for designing and optimizing nanoscale piezoelectric energy harvesters, as well as promoting their applications in emerging areas e.g. the internet of things, wearable devices, and self-powered nanosystems. PMID- 26871610 TI - Aberrant local striatal functional connectivity in attention deficit/hyperactivity disorder. AB - BACKGROUND: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. METHODS: We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. RESULTS: Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. CONCLUSIONS: Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD. PMID- 26871612 TI - Dinuclear Zinc(II) Macrocyclic Complex as Receptor for Selective Fluorescence Sensing of Pyrophosphate. AB - A new diethylenetriamine-derived macrocycle known as L, bearing 2-methylquinoline arms and containing m-xylyl spacers, was prepared in good yield by a one-pot [2 + 2] Schiff base condensation procedure, followed by reduction with sodium borohydride. Up to now this is the first hexaazamacrocycle with appended fluorophore units. Single-crystal X-ray diffraction determination of the dinuclear zinc(II) complex of L showed that metal centers are located at about 7.20(2) A from one another. This complex exhibits only weak fluorescence in aqueous solution, but the addition of 1 equiv of pyrophosphate (PPi) caused a 21 fold enhancement of the fluorescence intensity. The sensor response is linear up to a value of 10 MUM HPPi(3-) and has a detection limit of 300 nM. The receptor behaves as a highly selective sensor for pyrophosphate as other anions, including phosphate, phenylphosphate (PhP), adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP), failed to induce any fluorescence change and practically do not affect the fluorescence intensity of the sensor in the presence of HPPi(3-). Competition titrations carried out in aqueous solution at pH 7.4 [in 20 mM 3-(N-morpholino)propanesulfonic acid (MOPS) buffer] by spectrofluorometry revealed a high association constant value of 6.22 log units for binding of PPi by the dinuclear zinc(II) receptor, one of the highest reported values for colorimetric/fluorometric sensors able to work under real aqueous physiological conditions, while association constant values for binding of the other phosphorylated substrates are in the 5.51-4.03 log unit range. PMID- 26871613 TI - Relative Reactivity of Stable Ligated Boranes and a Borohydride Salt in Rhodium(II)-Catalyzed Boron-Hydrogen Insertion Reactions. AB - Relative reactivities of a series of neutral ligated boranes L-BH3 (where L is NHC, amine, pyridine, or phosphine) and the cyanoborohydride anion have been assessed in Rh(II)-catalyzed B-H insertion reactions with methyl 2-phenyl-2 diazoacetate. Stable alpha-boryl ester products were isolated by flash chromatography in all cases except for the salt product from cyanoborohydride. All of the substrates were either comparable to or more reactive than 1,4 cyclohexadiene, which is one of the most reactive substrates in C-H insertion reactions. The range of reactivity between the most reactive pyridine-borane and the least reactive phosphine-borane is a factor of approximately 40. PMID- 26871614 TI - Association between Adherence to the Mediterranean Diet and Presence of Nonalcoholic Fatty Liver Disease in Children. AB - OBJECTIVE: The study's objective was to analyze the association between the adherence to the Mediterranean diet (MD) and the presence of nonalcoholic fatty liver disease (NAFLD) in children. METHODS: The study consisted of three groups of children. Group 1 included obese/overweight children with recent diagnosis of NAFLD (n = 106, 12.4 +/- 2.6 years). Group 2 included obese children without NAFLD (n = 21, 11.3 +/- 2.6 years). Group 3 included the healthy children (without known chronic disease) with normal BMI (n = 54, 11.8 +/- 2.9 years). Compliance to the MD was assessed by the KIDMED index score. RESULTS: KIDMED index score in obese children with NAFLD, without NAFLD, and healthy children were 2.6 +/- 2.4, 4.6 +/- 1.2, and 6.2 +/- 1.9, respectively (p < 0.05 for group 1 versus 2, 1 versus 3, and 2 versus 3). Diet compliance was good in only 4.7% of the patients with NAFLD, whereas it was 31.5% in healthy children. KIDMED index score was negatively correlated with BMI (p < 0.05, r = -0.53), but no correlation was found with other parameters. The area under the receiver operation curve (AUROC) for predicting fatty liver disease in obese children (n = 127) with BMI and KIDMED index score was 0.78 (p < 0.05) and 0.24 (p < 0.05), respectively. BMI >26 has a sensitivity of 79.2% and specificity of 52.4%, and KIDMED index score <=3 has a sensitivity of 66.9% and specificity of 76.1%. CONCLUSIONS: MD is an inexpensive and nontoxic dietary regimen and may be used as a therapeutic option in obese children with NAFLD. PMID- 26871615 TI - Copula-based regression modeling of bivariate severity of temporary disability and permanent motor injuries. AB - The analysis of factors influencing the severity of the personal injuries suffered by victims of motor accidents is an issue of major interest. Yet, most of the extant literature has tended to address this question by focusing on either the severity of temporary disability or the severity of permanent injury. In this paper, a bivariate copula-based regression model for temporary disability and permanent injury severities is introduced for the joint analysis of the relationship with the set of factors that might influence both categories of injury. Using a motor insurance database with 21,361 observations, the copula based regression model is shown to give a better performance than that of a model based on the assumption of independence. The inclusion of the dependence structure in the analysis has a higher impact on the variance estimates of the injury severities than it does on the point estimates. By taking into account the dependence between temporary and permanent severities a more extensive factor analysis can be conducted. We illustrate that the conditional distribution functions of injury severities may be estimated, thus, providing decision makers with valuable information. PMID- 26871616 TI - Examining links between cognitive markers, movement initiation and change, and pedestrian safety in older adults. AB - OBJECTIVE: The purpose of this study was to determine the extent to which mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function, specifically executive functions, including spatial planning, visual attention, and within participant variability, differentially predicted collisions in the near and far sides of the road with increasing age. METHODS: Adults aged over 45 years participated in cognitive tests measuring executive function and visual attention (using Useful Field of View; UFoV((r))), mobility assessments (walking speed, sit-to-stand, self-reported mobility, and postural sway assessed using motion capture cameras), and gave road crossing choices in a two-way filmed real traffic pedestrian simulation. RESULTS: A stepwise regression model of walking speed, start-up delay variability, and processing speed) explained 49.4% of the variance in near-side crossing errors. Walking speed, start-up delay measures (average and variability), and spatial planning explained 54.8% of the variance in far-side unsafe crossing errors. Start-up delay was predicted by walking speed only (explained 30.5%). CONCLUSION: Walking speed and start-up delay measures were consistent predictors of unsafe crossing behaviours. Cognitive measures, however, differentially predicted near-side errors (processing speed), and far-side errors (spatial planning). These findings offer potential contributions for identifying and rehabilitating at-risk older pedestrians. PMID- 26871617 TI - Spectroscopic properties and location of the Ce(3+) energy levels in Y3Al2Ga3O12 and Y3Ga5O12 at ambient and high hydrostatic pressure. AB - In this study, we present the high pressure spectroscopy of Y3Al2Ga3O12 (YAGG) and Y3Ga5O12 (YGG) ceramics doped with Ce(3+) and Cr(3+). We have found that high hydrostatic pressure recovers the Ce(3+) luminescence in YGG. The pressure induced shifts of the ground state and the 5d1 excited state of Ce(3+) with respect to the conduction band edge were estimated. Our experimental data allowed us to also obtain the shifts of the conduction and valence band edges, and the ground state and the 5d1 state of Ce(3+) ions have been estimated with respect to the vacuum level. It has been shown that simple equivalence between the external hydrostatic pressure and intrinsic chemical pressure related to different compositions of the isostructural matrices does not exist in garnet lattices. PMID- 26871622 TI - A Mechanism for Somatic Brain Mosaicism. AB - Double-strand break repair is required for neural development, and brain cells contain somatic genomic variations. Now, Wei et al. demonstrate that neural stem and progenitor cells undergo very frequent DNA breaks in a very restricted set of genes involved in neural cell adhesion and synapse function. PMID- 26871623 TI - Pluripotency without Proliferation. AB - Mouse embryonic stem cells (mESCs) are capable of unlimited proliferation without losing pluripotency. Scognamiglio et al. now reveal that Myc depletion shifts mESCs into a dormant state reminiscent of embryonic diapause in which pluripotency remains fully preserved, thus decoupling pluripotency from proliferative programs. PMID- 26871618 TI - The Food and Drug Administration Office of Women's Health: Impact of Science on Regulatory Policy: An Update. AB - The U.S. Food and Drug Administration Office of Women's Health (FDA OWH) has supported women's health research for ~20 years, funding more than 300 studies on women's health issues, including research on diseases/conditions that disproportionately affect women in addition to the evaluation of sex differences in the performance of and response to medical products. These important women's health issues are studied from a regulatory perspective, with a focus on improving and optimizing medical product development and the evaluation of product safety and efficacy in women. These findings have influenced industry direction, labeling, product discontinuation, safety notices, and clinical practice. In addition, OWH-funded research has addressed gaps in the knowledge about diseases and medical conditions that impact women across the life span such as cardiovascular disease, pregnancy, menopause, osteoporosis, and the safe use of numerous medical products. PMID- 26871624 TI - Let It Go and Open Up, an Ensemble of Ion Channel Active States. AB - Ligand binding usually moves the target protein from an ensemble of inactive states to a well-defined active conformation. Matthies et al. flip this scheme around, finding that, for the magnesium channel CorA, loss of ligand binding induces an ensemble of conformations that turn the channel on. PMID- 26871625 TI - A Receptor for All Occasions. AB - Cells communicate with their environment, in part, through cell surface receptors. Engineering receptors that both sense arbitrary inputs and provide outputs orthogonal to endogenous signaling pathways has been a challenge. Now, Lim and colleagues report a system based on synthetic Notch receptors that allows independent control of both inputs and outputs in diverse cell types. PMID- 26871626 TI - A New Way to Diversify Antibodies by DNA Transposition. AB - While searching for new therapeutics against malaria, Lanzavecchia and colleagues discovered that antibodies can be diversified by DNA sequences encoded outside of antibody genes. PMID- 26871627 TI - The Cellular Phase of Alzheimer's Disease. AB - The amyloid hypothesis for Alzheimer's disease (AD) posits a neuron-centric, linear cascade initiated by Abeta and leading to dementia. This direct causality is incompatible with clinical observations. We review evidence supporting a long, complex cellular phase consisting of feedback and feedforward responses of astrocytes, microglia, and vasculature. The field must incorporate this holistic view and take advantage of advances in single-cell approaches to resolve the critical junctures at which perturbations initially amenable to compensatory feedback transform into irreversible, progressive neurodegeneration. PMID- 26871628 TI - Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation. AB - The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP. PMID- 26871629 TI - Distinct Circuits for the Formation and Retrieval of an Imprinted Olfactory Memory. AB - Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. We show that exposing newly hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted, but not for adult-learned, aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. PMID- 26871630 TI - Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells. AB - Repair of DNA double-strand breaks (DSBs) by non-homologous end joining is critical for neural development, and brain cells frequently contain somatic genomic variations that might involve DSB intermediates. We now use an unbiased, high-throughput approach to identify genomic regions harboring recurrent DSBs in primary neural stem/progenitor cells (NSPCs). We identify 27 recurrent DSB clusters (RDCs), and remarkably, all occur within gene bodies. Most of these NSPC RDCs were detected only upon mild, aphidicolin-induced replication stress, providing a nucleotide-resolution view of replication-associated genomic fragile sites. The vast majority of RDCs occur in long, transcribed, and late-replicating genes. Moreover, almost 90% of identified RDC-containing genes are involved in synapse function and/or neural cell adhesion, with a substantial fraction also implicated in tumor suppression and/or mental disorders. Our characterization of NSPC RDCs reveals a basis of gene fragility and suggests potential impacts of DNA breaks on neurodevelopment and neural functions. PMID- 26871631 TI - Self-Organization of Embryonic Genetic Oscillators into Spatiotemporal Wave Patterns. AB - In vertebrate embryos, somites, the precursor of vertebrae, form from the presomitic mesoderm (PSM), which is composed of cells displaying signaling oscillations. Cellular oscillatory activity leads to periodic wave patterns in the PSM. Here, we address the origin of such complex wave patterns. We employed an in vitro randomization and real-time imaging strategy to probe for the ability of cells to generate order from disorder. We found that, after randomization, PSM cells self-organized into several miniature emergent PSM structures (ePSM). Our results show an ordered macroscopic spatial arrangement of ePSM with evidence of an intrinsic length scale. Furthermore, cells actively synchronize oscillations in a Notch-signaling-dependent manner, re-establishing wave-like patterns of gene activity. We demonstrate that PSM cells self-organize by tuning oscillation dynamics in response to surrounding cells, leading to collective synchronization with an average frequency. These findings reveal emergent properties within an ensemble of coupled genetic oscillators. PMID- 26871633 TI - Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin. AB - Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. To understand how shelterin protects telomere ends, we investigated the structural organization of telomeric chromatin in human cells using super-resolution microscopy. We found that telomeres form compact globular structures through a complex network of interactions between shelterin subunits and telomeric DNA, but not by DNA methylation, histone deacetylation, or histone trimethylation at telomeres and subtelomeric regions. Mutations that abrogate shelterin assembly or removal of individual subunits from telomeres cause up to a 10-fold increase in telomere volume. Decompacted telomeres accumulate DDR signals and become more accessible to telomere-associated proteins. Recompaction of telomeric chromatin using an orthogonal method displaces DDR signals from telomeres. These results reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin mediated compaction of telomeric chromatin provides robust protection of chromosome ends against the DDR machinery. PMID- 26871632 TI - Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause. AB - Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state. PMID- 26871635 TI - Redefining the Translational Status of 80S Monosomes. AB - Fully assembled ribosomes exist in two populations: polysomes and monosomes. While the former has been studied extensively, to what extent translation occurs on monosomes and its importance for overall translational output remain controversial. Here, we used ribosome profiling to examine the translational status of 80S monosomes in Saccharomyces cerevisiae. We found that the vast majority of 80S monosomes are elongating, not initiating. Further, most mRNAs exhibit some degree of monosome occupancy, with monosomes predominating on nonsense-mediated decay (NMD) targets, upstream open reading frames (uORFs), canonical ORFs shorter than ~ 590 nt, and ORFs for which the total time required to complete elongation is substantially shorter than that required for initiation. Importantly, mRNAs encoding low-abundance regulatory proteins tend to be enriched in the monosome fraction. Our data highlight the importance of monosomes for the translation of highly regulated mRNAs. PMID- 26871634 TI - Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating. AB - CorA, the major Mg(2+) uptake system in prokaryotes, is gated by intracellular Mg(2+) (KD ~ 1-2 mM). X-ray crystallographic studies of CorA show similar conformations under Mg(2+)-bound and Mg(2+)-free conditions, but EPR spectroscopic studies reveal large Mg(2+)-driven quaternary conformational changes. Here, we determined cryo-EM structures of CorA in the Mg(2+)-bound closed conformation and in two open Mg(2+)-free states at resolutions of 3.8, 7.1, and 7.1 A, respectively. In the absence of bound Mg(2+), four of the five subunits are displaced to variable extents (~ 10-25 A) by hinge-like motions as large as ~ 35 degrees at the stalk helix. The transition between a single 5-fold symmetric closed state and an ensemble of low Mg(2+), open, asymmetric conformational states is, thus, the key structural signature of CorA gating. This mechanism is likely to apply to other structurally similar divalent ion channels. PMID- 26871638 TI - SnapShot: SMC Protein Complexes Part II. AB - This second of two SnapShots on SMC proteins depicts their roles at different stages of the eukaryotic cell cycle. The composition and architecture of SMC protein complexes and their regulators appear in SMC Protein Complexes Part I (available at http://www.cell.com/cell/pdf/S0092-8674%2815%2901690-6.pdf). To view this SnapShot, open or download the PDF. PMID- 26871636 TI - Multiplexed Intact-Tissue Transcriptional Analysis at Cellular Resolution. AB - In recently developed approaches for high-resolution imaging within intact tissue, molecular characterization over large volumes has been largely restricted to labeling of proteins. But volumetric nucleic acid labeling may represent a far greater scientific and clinical opportunity, enabling detection of not only diverse coding RNA variants but also non-coding RNAs. Moreover, scaling immunohistochemical detection to large tissue volumes has limitations due to high cost, limited renewability/availability, and restricted multiplexing capability of antibody labels. With the goal of versatile, high-content, and scalable molecular phenotyping of intact tissues, we developed a method using carbodiimide based chemistry to stably retain RNAs in clarified tissue, coupled with amplification tools for multiplexed detection. The resulting technology enables robust measurement of activity-dependent transcriptional signatures, cell identity markers, and diverse non-coding RNAs in rodent and human tissue volumes. The growing set of validated probes is deposited in an online resource for nucleating related developments from across the scientific community. PMID- 26871637 TI - Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. AB - While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms"). PMID- 26871640 TI - Caregivers' Self-Reported Absence of Social Support Networks is Related to Treatment Abandonment in Children With Cancer. AB - BACKGROUND: Treatment abandonment (TxA) is a primary cause of therapy failure in children with cancer in low-/middle-income countries. We explored the absence of social support network (SSN), among other predictive factors, and TxA in children with cancer in Cali, Colombia. PROCEDURE: In this prospective cohort study, we included children diagnosed with cancer at a public university hospital. A social worker and a psychologist administered semistructured questionnaires to patients' caregivers. We extracted information from the questionnaires about social, economic, and psychological conditions of the patients' families. Outcomes were death, relapse, and TxA. Failure either to start or to continue the planned course of curative treatment for 4 weeks or more was defined as TxA. We identified events with Cali's childhood cancer outcomes surveillance system (VIGICANCER). We adjusted the hazard ratios (HRs) for potential confounders using multivariate Cox regression analyses. RESULTS: Among 188 patients diagnosed from January 2011 to June 2013, 99 interviews were conducted. Median age was 5 years old (range: 0.3, 14.9), 53% were male, 17% were of Colombian-Indian ethnicity, and 68% lived in rural areas. The 2-year cumulative incidence of TxA was 21% (95% confidence interval [CI]: 13, 35) and the annual proportion was 14%. The adjusted HR for the absence of SSN was 4.9 (95% CI: 1.6, 15.3). CONCLUSIONS: We found a strong association between the absence of SSN and TxA that was independent of other covariates, including surrogate measures of wealth. Our findings highlight the imperative understanding of social ties and support surrounding children's families for planning strategies to prevent TxA. PMID- 26871641 TI - Are Home- and Community-Based Services Cost-Effective? PMID- 26871639 TI - GALNT14 genotype effectively predicts the therapeutic response in unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization. AB - AIM: Transcatheter arterial chemoembolization is currently the standard treatment in hepatocellular carcinoma patients with Barcelona Clinic Liver Cancer stage B. Genomic variants of GALNT14 were recently identified as effective predictors for chemotherapy responses in Barcelona Clinic Liver Cancer stage C patients. METHODS: We investigated the prognosis predictive value of GALNT14 genotypes in 327 hepatocelluar carcinoma patients treated by transcatheter arterial chemoembolization. RESULT: Cox proportional hazards model analysis showed that the genotype 'TT' was associated with shorter time-to-response (multivariate p < 0.001), time-to-complete-response (p = 0.004) and longer time-to-tumor progression (p < 0.001), compared with the genotype 'non-TT'. In patients with albumin <3.5 g/dl, genotype 'TT' was associated with longer overall survival (p = 0.027). Finally, genotype 'TT' correlated with higher cancer-to-noncancer ratios of GALNT14 protein levels, lower cancer-to-noncancer ratios of antiapoptotic cFLIP-S, and a clustered glycosylation pattern in the extracellular domain of death receptor 5. CONCLUSION: GALNT14 genotypes were significantly associated with clinical outcomes of transcatheter arterial chemoembolization. The differential status of extrinsic apoptotic signaling between cancerous and non cancerous tissues might underlie the clinical association. PMID- 26871642 TI - Access to Care Among Nonelderly Veterans. AB - BACKGROUND: Veteran access to care is an important policy issue that has not previously been examined with population-based survey data. OBJECTIVES: This study compares access to care for nonelderly adult Veterans versus comparable non Veterans, overall and within subgroups defined by simulated eligibility for health care from the Veterans Health Administration and by insurance status. RESEARCH DESIGN: We use household survey data from the Medical Expenditure Panel Survey from 2006 to 2011. We use iterative proportional fitting to standardize (control for) differences in age, sex, income, medical conditions, disability, Census region, and Metropolitan Statistical Area. SUBJECTS: Nonelderly Veterans and comparable non-Veterans. MEASURES: For medical, dental, and prescription medicine treatments, we use 4 access measures: delaying care, inability to obtain care, perceiving delay as a big problem, and perceiving inability to obtain care as a big problem. We also examine having a usual source of care. RESULTS: Frequencies of access barriers are similar for nonelderly Veterans and comparable non-Veterans for dental and prescription medicine treatments. For medical treatment, we find that Veterans eligible for VA health care and Veterans with VA use who are uninsured report fewer access problems than the comparable non Veteran populations for 2 measures: inability to obtain care and reporting inability to obtain care as a big problem. CONCLUSIONS: Our results show that uninsured Veterans, the most policy-relevant group, have better access to care than comparable non-Veterans. Our results highlight the importance of adjusting Veteran and non-Veteran comparisons to account for the higher than average health care needs of Veterans. PMID- 26871643 TI - A First Look at PCMH Implementation for Minority Veterans: Room for Improvement. AB - BACKGROUND: Implementation of Patient Aligned Care Teams (PACT), a patient centered medical home model, has been inconsistent among the >900 primary care facilities in the Veterans Health Administration. OBJECTIVE: Estimate if the degree of PACT implementation at a facility varied with the percentage of minority veteran patients at the facility. RESEARCH DESIGN: Cross-sectional, facility-level analysis of PACT implementation measures in 2012. SUBJECTS: Veterans Health Administration hospital-based and community-based primary care facilities. MEASURES: We used a previously validated PACT Implementation Progress Index (Pi) and its 8 domains: access, continuity of care, care coordination, comprehensiveness, self-management support, and patient-centered care and communication, shared decision-making domains, and team functioning. Facilities were categorized as low (<5.2%, n=208), medium (5.2%-25.8%, n=413), and high (>25.8%, n=206) percent minority based on the percent of their own veteran population. RESULTS: Most minority veterans received care in high minority (69%) and medium minority facilities (29%). In adjusted analyses, medium and high minority facilities scored 0.773 (P=0.009) and 0.930 (P=0.008) points lower on the Pi score relative to low minority facilities. Relative to low minority facilities, both medium and high minority facilities were less likely of having high Pi scores (>=2) and more likely of having low Pi scores (<=-2). Both medium and high minority facilities had the same 3 domain scores lower than low minority facilities (care coordination, comprehensiveness, and self-management). CONCLUSION: Overall PACT implementation varied with respect to the racial/ethnic composition of a facility, with medium and high minority facilities having a lower implementation scores. PMID- 26871644 TI - Availability of Care Concordant With Patient-centered Medical Home Principles Among Those With Chronic Conditions: Measuring Care Outcomes. AB - BACKGROUND: Care delivery redesign in the form of patient-centered medical home (PCMH) is considered as a potential solution to improve patient outcomes and reduce costs, particularly for patients with chronic conditions. But studies of prevalence or impact at the population level are rare. OBJECTIVES: We aimed to assess whether desired outcomes indicating better care delivery and patient centeredness were associated with receipt of care according to 3 important PCMH principles. RESEARCH DESIGN: We analyzed data from a representative population survey in California in 2009, focusing on a population with chronic condition who had a usual source of care. We used bivariate, logistic, and negative-binomial regressions. MEASURES: The indicators of PCMH concordant care included continuity of care (personal doctor), care coordination, and care management (individual treatment plan). Outcomes included flu shots, count of outpatient visits, any emergency department visit, timely provider communication, and confidence in self care. RESULTS: We found that patients whose care was concordant with all 3 PCMH principles were more likely to receive flu shots, more outpatient care, and timely response from providers. Concordance with 2 principles led to some desired outcomes. Concordance with only 1 principle was not associated with desired outcomes. CONCLUSIONS: Patients who received care that met 3 key aspects of PCMH: coordination, continuity, and management, had better quality of care and more efficient use of the health care system. PMID- 26871645 TI - Overcrowding in Psychiatric Wards is Associated With Increased Risk of Adverse Incidents. AB - OBJECTIVE: To study the association between bed occupancy in psychiatric wards and rate of adverse incidents (AIs) including aggressive behavior and falls. METHODS: This is a retrospective study analyzing bed occupancy and AIs' data in 4 closed wards in a state psychiatric hospital in Israel over a 20-month period. Ward-level daily records were extracted from the hospital's electronic admission discharge and AI registries, creating a log of 609 days for each of the 4 wards. Relationships between gross and net bed occupancy and AIs rate were calculated, in general and for each ward and type of incidents. RESULTS: Average gross occupancy was 106+/-14.8% and net occupancy was 96.4+/-15.6%. Gross occupancy >100% was recorded in 51% of days. Net occupancy was higher on days with at least 1 incident than on no-incident days (98.6+/-14.8% vs. 95.7+/-15.7%, P<0.0001). AIs occurred in 18.6% of days in the lowest occupancy quadrant (up to 85% occupancy), compared with 26.7% of days in the highest occupancy quadrant (106% and above). Moreover, aggressive behavior-type incidents were significantly lower in the lowest occupancy quadrant days compared with the highest occupancy quadrant (8.3% vs. 14.1%, P<0.01). Evidence of a dose-response effect of bed occupancy on AIs rate was found. CONCLUSIONS: Overoccupancy is prevalent in psychiatric wards and is associated with an increased rate of aggressive AIs and falls. Policy makers should be convinced about the necessity to reduce overcrowding in psychiatric wards and to improve safety of inpatient facilities. PMID- 26871646 TI - High-resolution core-level photoemission measurements on the pentacene single crystal surface assisted by photoconduction. AB - Upon charge carrier transport behaviors of high-mobility organic field effect transistors of pentacene single crystal, effects of ambient gases and resultant probable 'impurities' at the crystal surface have been controversial. Definite knowledge on the surface stoichiometry and chemical composites is indispensable to solve this question. In the present study, high-resolution x-ray photoelectron spectroscopy (XPS) measurements on the pentacene single crystal samples successfully demonstrated a presence of a few atomic-percent of (photo-)oxidized species at the first molecular layer of the crystal surface through accurate analyses of the excitation energy (i.e. probing depth) dependence of the C1s peak profiles. Particular methodologies to conduct XPS on organic single crystal samples, without any charging nor damage of the sample in spite of its electric insulating character and fragility against x-ray irradiation, is also described in detail. PMID- 26871647 TI - Health Behavior Change Interventions for Teenage and Young Adult Cancer Survivors: A Systematic Review. AB - PURPOSE: It is important that teenage and young adult (TYA) cancer survivors adopt a healthy lifestyle, since health vulnerabilities associated with their diagnosis and treatment may be exacerbated by poor health behaviors. This review aims to synthesize the current literature on health behavior change interventions created specifically for TYA-aged cancer survivors. METHOD: MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched for studies investigating interventions targeting one or more health behaviors, including: physical activity, diet, smoking cessation, and alcohol consumption. Studies were eligible for review if the study population were defined as TYA cancer survivors and the mean age of the sample was younger than 30 years of age. RESULTS: Twelve studies were identified, of which nine were randomized controlled trials. Physical activity was the most commonly targeted health behavior. Six of the 12 interventions included within this review were successful in changing health behavior. Due to the heterogeneity of intervention characteristics, the relationship between intervention efficacy or outcome and intervention content, delivery mode, or theoretical framework was not discernible. Nevertheless, trends emerged relating to the delivery and content of health behavior interventions designed specifically for TYA cancer survivors. CONCLUSION: More research is required to identify the most effective means of promoting health behavior change among the TYA cancer survivor population. Specifically, future research should focus on providing evidence of the efficiency and feasibility of interventions that use online technologies to facilitate remote intervention delivery and peer support. PMID- 26871648 TI - Editorial: Modified extended approach improves recovery following spinal accessory to suprascapular nerve transfer. PMID- 26871649 TI - Results of spinal accessory to suprascapular nerve transfer in 110 patients with complete palsy of the brachial plexus. AB - OBJECTIVE Transfer of the spinal accessory nerve to the suprascapular nerve is a common procedure, performed to reestablish shoulder motion in patients with total brachial plexus palsy. However, the results of this procedure remain largely unknown. METHODS Over an 11-year period (2002-2012), 257 patients with total brachial plexus palsy were operated upon in the authors' department by a single surgeon and had the spinal accessory nerve transferred to the suprascapular nerve. Among these, 110 had adequate follow-up and were included in this study. Their average age was 26 years (SD 8.4 years), and the mean interval between their injury and surgery was 5.2 months (SD 2.4 months). Prior to 2005, the suprascapular and spinal accessory nerves were dissected through a classic supraclavicular L-shape incision (n = 29). Afterward (n = 81), the spinal accessory and suprascapular nerves were dissected via an oblique incision, extending from the point at which the plexus crossed the clavicle to the anterior border of the trapezius muscle. In 17 of these patients, because of clavicle fractures or dislocation, scapular fractures or retroclavicular scarring, the incision was extended by detaching the trapezius from the clavicle to expose the suprascapular nerve at the suprascapular fossa. In all patients, the brachial plexus was explored and elbow flexion reconstructed by root grafting (n = 95), root grafting and phrenic nerve transfer (n = 6), phrenic nerve transfer (n = 1), or third, fourth, and fifth intercostal nerve transfer. Postoperatively, patients were followed for an average of 40 months (SD 13.7 months). RESULTS Failed recovery, meaning less than 30 degrees abduction, was observed in 10 (9%) of the 110 patients. The failure rate was 25% between 2002 and 2004, but dropped to 5% after the staged/extended approach was introduced. The mean overall range of abduction recovery was 58.5 degrees (SD 26 degrees ). Comparing before and after distal suprascapular nerve exploration (2005-2012), the range of abduction recovery was 45 degrees (SD 25.1 degrees ) versus 62 degrees (SD 25.3 degrees ), respectively (p = 0.002). In patients who recovered at least 30 degrees of abduction, recovery of elbow flexion to at least an M3 level of strength increased the range of abduction by an average of 13 degrees (p = 0.01). Before the extended approach, 2 (7%) of 29 patients recovered active external rotation of 20 degrees and 120 degrees . With the staged/extended approach, 32 (40%) of 81 recovered some degree of active external rotation. In these patients, the average range of motion measured from the thorax was 87 degrees (SD 40.6 degrees ). CONCLUSIONS In total palsies of the brachial plexus, using the spinal accessory nerve for transfer to the suprascapular nerve is reliable and provides some recovery of abduction for a large majority of patients. In a few patients, a more extensive approach to access the suprascapular nerve, including, if necessary, dissection in the suprascapular fossa, may enhance outcomes. PMID- 26871650 TI - Ectopic ganglion in cauda equina: case report. AB - Macroscopic ectopic or heterotopic ganglionic tissue within the cauda equina is a very rare pathological finding and is usually associated with spinal dysraphism. However, it may mimic genuine neoplasms of the cauda equina. The authors describe a 29-year-old woman with a history of back pain, right leg pain, and urinary incontinence in whom imaging demonstrated an enhancing mass located in the cauda equina at the L1-2 interspace. The patient subsequently underwent biopsy and was found to have a focus of ectopic ganglionic tissue that was 1.3 cm in greatest dimension. To the authors' knowledge, ectopic or heterotopic ganglionic tissue within the cauda equina in a patient without evidence of spinal dysraphism has never been reported. This patient presented with imaging and clinical findings suggestive of a neoplasm, and an open biopsy proved the lesion to be ectopic ganglionic tissue. The authors suggest that ectopic ganglionic tissue be added to the list of differential diagnoses of a space-occupying lesion arising from the cauda equina. PMID- 26871651 TI - Prognostic value of magnetic resonance imaging findings in patients with sciatica. AB - OBJECTIVE This study aimed to determine the prognostic value of MRI variables to predict outcome in patients with herniated disc-related sciatica, and whether MRI could facilitate the decision making between early surgery and prolonged conservative care in these patients. METHODS A prospective observational evaluation of patients enrolled in a randomized trial with 1-year follow-up was completed. A total of 283 patients with sciatica who had a radiologically confirmed disc herniation were randomized either to surgery or to prolonged conservative care with surgery if needed. Outcome measures were recovery and leg pain severity. Recovery was registered on a 7-point Likert scale. Complete/near complete recovery was considered a satisfactory outcome. Leg pain severity was measured on a 0- to 100-mm visual analog scale. Multiple MRI characteristics of the degenerated disc herniation were independently scored by 3 spine experts. Cox models were used to study the influence of MRI variables on rate of recovery, and linear mixed models were used to determine the predictive value of MRI variables for leg pain severity during follow-up. The interaction of each MRI predictor with treatment allocation was tested. There were no study-specific conflicts of interest. RESULTS Baseline MRI variables associated with less leg pain severity were the reader's assessment of presence of nerve root compression (p < 0.001), and assessment of extrusion compared with protrusion of the disc herniation (p = 0.006). Both variables tended to be associated, but not significantly, with satisfactory outcome during follow-up (HR 1.45, 95% CI 0.93-2.24, and HR 1.24, 95% CI 0.96-1.61, respectively). The size of disc herniation at baseline was not associated with outcome. There was no significant change in the effects between treatment groups. CONCLUSIONS MRI assessment of the presence of nerve root compression and extrusion of a herniated disc at baseline was associated with less leg pain during 1-year follow-up, irrespective of a surgical or conservative treatment. MRI findings seem not to be helpful in determining which patients might fare better with early surgery compared with a strategy of prolonged conservative care. Clinical trial registration no.: ISRCTN26872154 ( controlled trials.com ). PMID- 26871652 TI - Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis. AB - OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor-alpha, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord. PMID- 26871653 TI - De Novo Mutation in ABCC9 Causes Hypertrichosis Acromegaloid Facial Features Disorder. AB - A 13-year-old Egyptian girl with generalized hypertrichosis, gingival hyperplasia, coarse facial appearance, no cardiovascular or skeletal anomalies, keloid formation, and multiple labial frenula was referred to our clinic for counseling. Molecular analysis of the ABCC9 gene showed a de novo missense mutation located in exon 27, which has been described previously with Cantu syndrome. An overlap between Cantu syndrome, acromegaloid facial syndrome, and hypertrichosis acromegaloid facial features disorder is apparent at the phenotypic and molecular levels. The patient reported here gives further evidence that these syndromes are an expression of the ABCC9-related disorders, ranging from hypertrichosis and acromegaloid facies to the severe end of Cantu syndrome. PMID- 26871654 TI - Concept Development of the Eindhoven Diabetes Education Simulator Project. AB - OBJECTIVE: This study was designed to define the concept of an educational diabetes game following a user-centered design approach. MATERIALS AND METHODS: The concept development of the Eindhoven Diabetes Education Simulator (E-DES) project can be divided in two phases: concept generation and concept evaluation. Four concepts were designed by the multidisciplinary development team based on the outcomes of user interviews. Four other concepts resulted from the Diabetes Game Jam. Several users and experts evaluated the concepts. These user evaluations and a feasibility analysis served as input for an overall evaluation and discussion by the development team resulting in the final concept choice. RESULTS: The four concepts of the development team are a digital board game, a quiz platform, a lifestyle simulator, and a puzzle game. The Diabetes Game Jam resulted in another digital board game, two mobile swipe games, and a fairy tale themed adventure game. The combined user evaluations and feasibility analysis ranked the quiz platform and the digital board game equally high. Each of these games fits one specific subgroup of users best: the quiz platform best fits an eager-to-learn, more individualistic patient, whereas the board game best fits a less-eager-to-learn, family-oriented patient. The choice for a specific concept is therefore highly dependent on the choice of our specific target audience. CONCLUSIONS: The user-centered design approach with multiple evaluations has enabled us to choose the most promising concept from eight different options. A digital board game is chosen for further development because the target audience for E-DES is the less-motivated, family-oriented patients. PMID- 26871655 TI - Effective recovery of poly-beta-hydroxybutyrate (PHB) biopolymer from Cupriavidus necator using a novel and environmentally friendly solvent system. AB - This work demonstrates a significant advance in bioprocessing for a high-melting lipid polymer. A novel and environmental friendly solvent mixture, acetone/ethanol/propylene carbonate (A/E/P, 1:1:1 v/v/v) was identified for extracting poly-hydroxybutyrate (PHB), a high-value biopolymer, from Cupriavidus necator. A set of solubility curves of PHB in various solvents was established. PHB recovery of 85% and purity of 92% were obtained from defatted dry biomass (DDB) using A/E/P. This solvent mixture is compatible with water, and from non defatted wet biomass, PHB recovery of 83% and purity of 90% were achieved. Water and hexane were evaluated as anti-solvents to assist PHB precipitation, and hexane improved recovery of PHB from biomass to 92% and the purity to 93%. A scale-up extraction and separation reactor was designed, built and successfully tested. Properties of PHB recovered were not significantly affected by the extraction solvent and conditions, as shown by average molecular weight (1.4 * 10(6) ) and melting point (175.2 degrees C) not being different from PHB extracted using chloroform. Therefore, this biorenewable solvent system was effective and versatile for extracting PHB biopolymers. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:678-685, 2016. PMID- 26871656 TI - Management of aniridia and iris defects: an update on iris prosthesis options. AB - PURPOSE OF REVIEW: This review examines the advantages and limitations of the various iris prostheses as treatment for aniridia. RECENT FINDINGS: Multiple prosthetic iris devices have been developed for implantation in eyes with aniridia. However, none is currently approved for use in the USA. SUMMARY: Aniridia can be congenital or traumatic in etiology and can lead to glare and other visual disturbances. Treatment options include colored contact lenses, corneal tattooing, and corneal stromal implants, although these carry significant risks of infection and corneal scarring. Prosthetic iris devices can often simultaneously treat aphakia or cataract as well as aniridia, and various models are currently available around the world from Morcher GMBH (Kapuzinerweg 12, 70374 Stuttgart, Germany), Ophtec USA Inc. (6421 Congress Ave Suite 12, Boca Raton, FL 33487, USA) and HumanOptics (Erlangen, Germany). Surgical planning and technique are important in optimizing the safety of these devices. The CustomFlex iris prosthesis from HumanOptics can be implanted within the capsular bag or ciliary sulcus with scleral fixation and offers excellent cosmetic outcomes. At present, the HumanOptics prosthetic iris is being investigated in a multicenter clinical trial. PMID- 26871657 TI - Systemic safety of intravitreal anti-vascular endothelial growth factor agents in age-related macular degeneration. AB - PURPOSE OF REVIEW: The purpose of review is to summarize the literature addressing nonocular adverse events in patients with neovascular age-related macular degeneration treated with intravitreal vascular endothelial growth factor (VEGF) inhibitors and to present possible mechanisms of effect. RECENT FINDINGS: The incidence of overall nonocular serious adverse events varied from 0 to 39.3% and nonocular adverse events ranged from 0 to 86.9%. Few studies have reported a significant association between use of intravitreal anti-VEGF agents and overall incidence of adverse events, stroke, myocardial infarction, nonocular hemorrhage and death, with overall greater concern in patients treated with bevacizumab. Additionally, history of stroke or other arterial thromboembolic event may be a risk factor for future stroke in patients treated with intravitreal anti-VEGF agents. Theories explaining the mechanisms of increased risk of nonocular adverse events secondary to anti-VEGF agent use surround the necessity of VEGF for the normal functioning of the endothelium and the damage incurred with use of anti VEGF agents. SUMMARY: Current data are insufficient to definitively conclude that intravitreal anti-VEGF agents are safe, although there is a trend toward an overall favorable systemic safety profile. Caution should be exerted in patients with a history of cardiovascular disease, as these patients may be at greater risk for nonocular serious adverse events. PMID- 26871659 TI - Identification of a new cyathane diterpene that induces mitochondrial and autophagy-dependent apoptosis and shows a potent in vivo anti-colorectal cancer activity. AB - Diterpenes has been reported to possess multiple bioactivities consisting of anti microbial and anti-inflammatory properties. This study reveals a new cyathane type diterpene (cyathin Q) from the culture of the fungus Cyathus africanus by bioactivity-guided separation. The structure of cyathin Q was determined based on spectroscopic measurements (NMR and MS). The bioactivity evaluation shows that cyathin Q has a strong anticancer activity against HCT116 cells and Bax-deficient HCT116 in vitro and in vivo. This compound induced hallmarks of apoptotic events in HCT116 cells, including caspase activation, cytochrome c release, poly (ADP ribose) polymerase (PARP) cleavage, and depolarization of the mitochondrial inner transmembrane potential. This process is accompanied with the increased mitochondrial ROS, down-regulation of Bcl-2 protein, and up-regulation of Bim protein. We also observed the cleavage of autophagy-related protein ATG5 in cyathin Q-induced apoptosis. Taken together, our study identified a new fungal diterpene that exhibited anticancer activity via induction of mitochondria and autophagy-dependent apoptosis in HCT116 cells. PMID- 26871658 TI - Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents. AB - A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 MUM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m DNA complex which might further block DNA replication to exert the powerful bioactivities. PMID- 26871660 TI - Discovery of a new selective inhibitor of A Disintegrin And Metalloprotease 10 (ADAM-10) able to reduce the shedding of NKG2D ligands in Hodgkin's lymphoma cell models. AB - Hodgkin's lymphoma (HL) is the most common malignant lymphoma in young adults in the western world. This disease is characterized by an overexpression of ADAM-10 with increased release of NKG2D ligands, involved in an impaired immune response against tumor cells. We designed and synthesized two new ADAM-10 selective inhibitors, 2 and 3 based on previously published ADAM-17 selective inhibitor 1. The most promising compound was the thiazolidine derivative 3, with nanomolar activity for ADAM-10, high selectivity over ADAM-17 and MMPs and good efficacy in reducing the shedding of NKG2D ligands (MIC-B and ULBP3) in three different HL cell lines at non-toxic doses. Molecular modeling studies were used to drive the design and X-ray crystallography studies were carried out to explain the selectivity of 3 for ADAM-10 over MMPs. PMID- 26871661 TI - WHAT'S NEW IN SHOCK? MARCH 2016. PMID- 26871662 TI - ADQI XIV PREFACE. PMID- 26871663 TI - ACUTE DIALYSIS QUALITY INITIATIVE (ADQI) XIV SEPSIS PHENOTYPES AND TARGETS FOR BLOOD PURIFICATION IN SEPSIS: THE BOGOTA CONSENSUS. AB - Despite widespread use, there is currently no consensus on how extracorporeal blood purification therapies should be applied or studied in patients with sepsis. One major obstacle has been the lack of clear descriptions of specific sepsis phenotypes tied to mechanisms that would permit the identification of molecular targets. Current evidence suggests that sepsis-related morbidity and mortality involve widely different clinical phenotypes that variably include mitochondrial dysfunction, abnormalities of vascular biology including endothelial dysfunction and coagulopathy, epithelial dysfunction, and immune suppression and dysregulation. While most cases of sepsis involve some element of all of these pathobiologic processes, the magnitude of each varies greatly from patient to patient in part as a result of the pathogen and in part related to host-specific factors. Thus, the purpose of the fourteenth international consensus conference of acute dialysis quality initiative was to develop consensus for a conceptual model of sepsis-induced organ failure that can be treated by extracorporeal blood purification and possibly also with drugs or other therapies. We assembled a group of experts from around the world and used a modified Delphi method to reach consensus. Specific findings and recommendations for future research are provided in the four accompanying papers. PMID- 26871666 TI - IL-13 and the Airway Epithelium. It Is All in the Genes. PMID- 26871667 TI - Making Precision Medicine Socially Precise. Take a Deep Breath. PMID- 26871664 TI - THE ENDOTHELIUM IN SEPSIS. AB - Sepsis affects practically all aspects of endothelial cell (EC) function and is thought to be the key factor in the progression from sepsis to organ failure. Endothelial functions affected by sepsis include vasoregulation, barrier function, inflammation, and hemostasis. These are among other mechanisms often mediated by glycocalyx shedding, such as abnormal nitric oxide metabolism, up regulation of reactive oxygen species generation due to down-regulation of endothelial-associated antioxidant defenses, transcellular communication, proteases, exposure of adhesion molecules, and activation of tissue factor. This review covers current insight in EC-associated hemostatic responses to sepsis and the EC response to inflammation. The endothelial cell lining is highly heterogeneous between different organ systems and consequently also in its response to sepsis. In this context, we discuss the response of the endothelial cell lining to sepsis in the kidney, liver, and lung. Finally, we discuss evidence as to whether the EC response to sepsis is adaptive or maladaptive. This study is a result of an Acute Dialysis Quality Initiative XIV Sepsis Workgroup meeting held in Bogota, Columbia, between October 12 and 15, 2014. PMID- 26871668 TI - Innate Lymphoid Cells and Acute Respiratory Distress Syndrome. PMID- 26871665 TI - MITOCHONDRIAL FUNCTION IN SEPSIS. AB - Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long-term morbidity and mortality. Clearly, interest is mitochondrial function both as a target for intracellular injury and response to extrinsic stress have been a major focus of basic science and clinical research into the pathophysiology of acute illness. However, mitochondria have multiple metabolic and signaling functions that may be central in both the expression of sepsis and its ultimate outcome. In this review, the authors address five primary questions centered on the role of mitochondria in sepsis. This review should be used both as a summary source in placing mitochondrial physiology within the context of acute illness and as a focal point for addressing new research into diagnostic and treatment opportunities these insights provide. PMID- 26871669 TI - Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Smooth Muscle. A Novel Role in Cystic Fibrosis Airway Obstruction. PMID- 26871670 TI - Seeking an Accurate, Point-of-Contact Diagnostic Test for Bacterial Pneumonia. PMID- 26871671 TI - Mucking around in the Genome: MUC5B in Idiopathic Pulmonary Fibrosis. PMID- 26871672 TI - Mucins MUC5B and MUC5AC in Distal Airways and Honeycomb Spaces: Comparison among Idiopathic Pulmonary Fibrosis/Usual Interstitial Pneumonia, Fibrotic Nonspecific Interstitial Pneumonitis, and Control Lungs. PMID- 26871673 TI - MUC5B Promoter Variant rs35705950 Affects MUC5B Expression in the Distal Airways in Idiopathic Pulmonary Fibrosis. PMID- 26871674 TI - Neurocritical Care Society Views on "Potentially Inappropriate Treatments in Intensive Care Units". PMID- 26871676 TI - "Want" Is a Four-Letter Word in End-of-Life Communication. PMID- 26871677 TI - What is Legionnaires' Disease? PMID- 26871675 TI - Reply: Neurocritical Care Society Views on "Potentially Inappropriate Treatments in Intensive Care Units". PMID- 26871678 TI - Treatment patterns and characteristics of older antipsychotic users in Germany. AB - The aim of this study was to investigate the characteristics and treatment patterns of older antipsychotic (AP) users in Germany. We carried out a cohort study in the German Pharmacoepidemiological Research Database and identified new AP users aged at least 65 years between 2005 and 2011. Possible indications, comedication, and information on persistence and adherence, concurrent multiple use, and switch of APs were assessed. Overall, 298,847 individuals were included in the cohort. Almost 70% entered the cohort with a typical antipsychotic (TAP). Melperone (23.4%) was used most frequently, followed by promethazine (18.3%), sulpiride (11.0%), and risperidone (10.3%). AP users had a low prevalence of schizophrenia and bipolar disorders in contrast to dementia. Initiators of atypical antipsychotics had more treatment episodes compared with TAPs (median 3 vs. 2), but lower median persistence (14 vs. 22 days). Persistence was also lower in patients with, rather than without, dementia. The overall percentage of concurrent multiple use and switch to other APs was low with 5.6%, but higher in patients with, rather than without, dementia. In conclusion, APs were used for a broad range of indications, mostly other than schizophrenia and bipolar disorders. Low persistence and a high number of treatment episodes suggest frequent 'as-needed' treatment, especially in dementia patients. PMID- 26871679 TI - From Ethical Exceptionalism to Ethical Exceptions: The Rule and exception Model and the Changing Meaning of Ethics In German Bioregulation. AB - Germany is an interesting case with respect to the governance of reprogenetics. It has a strong profile in the technosciences and high aims regarding the global bioeconomy, yet her regulation of human genetics, reproductive medicine and embryo research has for a long time been rather restrictive. German biopolitical exceptionalism has often been explained by reference to Catholicism and the legacy of the Nazi past. The Germans, so goes the common story, have learnt the lessons of history and translated them into unconditional respect for human dignity, which in turn translates into unconditional protection of human life, including the human embryo, and the firm repudiation of any eugenic distinction between 'life worth to live' and 'life not worth to live'. This, however, is not the whole story. Alongside deontological strictness we find another strand of governing body politics and reprogenetics in Germany, the rule-and-exception model, running from the mid-1970s abortion law via the 2002 Stem Cell Act to the 2011 regulation of pre-implantation genetic diagnosis. In contrast to the former, that strongly draws on Kant and his concept of human dignity, the latter bears resemblances to Carl Schmitt's concept of state of exception. The article will show that the rule-and-exception model builds the exception into the rule and transforms the meaning and mandate of ethics, namely from safeguarding ethical standards to deciding about the exception. Given that the exception has now tended to become the rule, the question is whether the lessons of history will govern German reprogenetics for much longer. PMID- 26871680 TI - Kinetics of cellular uptake of viruses and nanoparticles via clathrin-mediated endocytosis. AB - Several viruses exploit clathrin-mediated endocytosis to gain entry into host cells. This process is also used extensively in biomedical applications to deliver nanoparticles (NPs) to diseased cells. The internalization of these nano objects is controlled by the assembly of a clathrin-containing protein coat on the cytoplasmic side of the plasma membrane, which drives the invagination of the membrane and the formation of a cargo-containing endocytic vesicle. Current theoretical models of receptor-mediated endocytosis of viruses and NPs do not explicitly take coat assembly into consideration. In this paper we study cellular uptake of viruses and NPs with a focus on coat assembly. We characterize the internalization process by the mean time between the binding of a particle to the membrane and its entry into the cell. Using a coarse-grained model which maps the stochastic dynamics of coat formation onto a one-dimensional random walk, we derive an analytical formula for this quantity. A study of the dependence of the mean internalization time on NP size shows that there is an upper bound above which this time becomes extremely large, and an optimal size at which it attains a minimum. Our estimates of these sizes compare well with experimental data. We also study the sensitivity of the obtained results on coat parameters to identify factors which significantly affect the internalization kinetics. PMID- 26871681 TI - Associations between ADHD symptoms and smoking outcome expectancies in a non clinical sample of daily cigarette smokers. AB - BACKGROUND AND OBJECTIVES: Smoking outcome expectancies for positive reinforcement (PR: beliefs that smoking produces desirable outcomes) and negative reinforcement (NR: beliefs that smoking alleviates negative affect) are modifiable cognitive manifestations of affect-mediated smoking motivation. Based on prior data and theory, we hypothesized that NR and PR expectancies are associated with ADHD symptom levels in a non-clinical sample of cigarette smokers. (Am J Addict 2016; XX:XX -XX) METHODS: Daily cigarette smokers (N = 256) completed self-report measures of ADHD symptoms and smoking outcome expectancies. Cross-sectional associations of overall ADHD symptomatology and the ADHD symptom dimensions of inattention (IN: difficulty concentrating and distractibility) and hyperactivity impulsivity (HI: poor inhibitory control and motor activity restlessness) with PR and NR smoking outcome expectancies were examined. RESULTS: Higher levels of overall, IN and HI ADHD symptoms were positively associated with NR smoking expectancies after statistically controlling for anxiety, depression, alcohol/drug use problems, nicotine dependence, and other smoking expectancies. Although neither HI nor IN symptom dimensions exhibited empirically unique relations to NR expectancies over and above one another, the collective variance across IN and HI was associated with NR expectancies. PR expectancies were not associated with ADHD symptoms. DISCUSSION AND CONCLUSIONS: Although PR and NR expectancies may be important etiological influences in the overall population of smokers, NR outcome expectancies appear to be disproportionately expressed in smokers with elevated ADHD symptoms. Cognitive manifestations of NR motivation, which may be modifiable via intervention, are prominent in smokers with elevated ADHD symptoms. SCIENTIFIC SIGNIFICANCE: Beliefs that smoking alleviates negative affect may underlie ADHD-smoking comorbidity. PMID- 26871682 TI - Self-assembled monolayers based spintronics: from ferromagnetic surface functionalization to spin-dependent transport. AB - Chemically functionalized surfaces are studied for a wide range of applications going from medicine to electronics. Whereas non-magnetic surfaces have been widely studied, functionalization of magnetic surfaces is much less common and has almost never been used for spintronics applications. In this article we present the functionalization of La2/3Sr1/3MnO3, a ferromagnetic oxide, with self assembled monolayers for spintronics. La2/3Sr1/3MnO3 is the prototypical half metallic manganite used in spintronics studies. First, we show that La2/3Sr1/3MnO3 can be functionalized by alkylphosphonic acid molecules. We then emphasize the use of these functionalized surfaces in spintronics devices such as magnetic tunnel junctions fabricated using a nano-indentation based lithography technique. The observed exponential increase of tunnel resistance as a function of alkyl chain length is a direct proof of the successful connection of molecules to ferromagnetic electrodes. For all alkyl chains studied we obtain stable and robust tunnel magnetoresistance, with effects ranging from a few tens to 10 000%. These results show that functionalized electrodes can be integrated in spintronics devices and open the door to a molecular engineering of spintronics. PMID- 26871683 TI - Multimodal optical analysis of meningioma and comparison with histopathology. AB - Meningioma is the most frequent primary central nervous system tumor. The risk of recurrence and the prognosis are correlated with the extent of the resection that ideally encompasses the infiltrated dura mater and, if required, the infiltrated bone. No device can deliver real-time intraoperative histopathological information on the tumor environment to help the neurosurgeon to achieve a gross total removal. This study assessed the abilities of nonlinear microscopy to provide relevant and real-time data to help resection of meningiomas. Nine human meningioma samples (four World Health Organization Grade I, five Grade II) were analyzed using different optical modalities: spectral analysis and imaging, lifetime measurements, fluorescence lifetime imaging microscopy, fluorescence emitted under one- and two-photon excitation and the second-harmonic generation signal imaging using a multimodal setup. Nonlinear microscopy produced images close to histopathology as a gold standard. The second-harmonic generation signal delineated the collagen background and two-photon fluorescence underlined cell cytoplasm. The matching between fluorescence images and Hematoxylin and Eosin staining was possible in all cases. Grade I meningioma emitted less autofluorescence than Grade II meningioma and Grade II meningioma exhibited a distinct lifetime value. Autofluorescence was correlated with the proliferation rates and seemed to explain the observed differences between Grade I and II meningiomas. This preliminary multimodal study focused on human meningioma samples confirms the potential of tissue autofluorescence analysis and nonlinear microscopy in helping intraoperatively neurosurgeons to reach the actual boundaries of the tumor infiltration. Correspondence between H&E staining (top pictures) and the two-photon fluorescence imaging (bottom pictures). PMID- 26871684 TI - Direct Conversion of Greenhouse Gas CO2 into Graphene via Molten Salts Electrolysis. AB - Producing graphene through the electrochemical reduction of CO2 remains a great challenge, which requires precise control of the reaction kinetics, such as diffusivities of multiple ions, solubility of various gases, and the nucleation/growth of carbon on a surface. Here, graphene was successfully created from the greenhouse gas CO2 using molten salts. The results showed that CO2 could be effectively fixed by oxygen ions in CaCl2-NaCl-CaO melts to form carbonate ions, and subsequently electrochemically split into graphene on a stainless steel cathode; O2 gas was produced at the RuO2-TiO2 inert anode. The formation of graphene in this manner can be ascribed to the catalysis of active Fe, Ni, and Cu atoms at the surface of the cathode and the microexplosion effect through evolution of CO in between graphite layers. This finding may lead to a new generation of proceedures for the synthesis of high value-added products from CO2, which may also contribute to the establishment of a low-carbon and sustainable world. PMID- 26871685 TI - Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR. AB - Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ-specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high-resolution magic-angle-spinning (HR-MAS) NMR and solution NMR-based metabolic profiling were used to investigate dose-dependent metabolic changes in multiple organs and tissues--including the jejunum, spleen, liver, and plasma--of rats exposed to X-ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low-dose (2 Gy) and high-dose (6 Gy) X-ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high-dose compared with the low-dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X-ray radiation. PMID- 26871686 TI - Bone Marrow Stromal Cells Promote Neuronal Restoration in Rats with Traumatic Brain Injury: Involvement of GDNF Regulating BAD and BAX Signaling. AB - BACKGROUND/AIMS: To investigate the effects of bone marrow stromal cells (BMSCs) and underlying mechanisms in traumatic brain injury (TBI). METHODS: Cultured BMSCs from green fluorescent protein-transgenic mice were isolated and confirmed. Cultured BMSCs were immediately transplanted into the regions surrounding the injured-brain site to test their function in rat models of TBI. Neurological function was evaluated by a modified neurological severity score on the day before, and on days 7 and 14 after transplantation. After 2 weeks of BMSC transplantation, the brain tissue was harvested and analyzed by microarray assay. And the coronal brain sections were determined by immunohistochemistry with mouse anti-growth-associated protein-43 kDa (anti-GAP-43) and anti-synaptophysin to test the effects of transplanted cells on the axonal regeneration in the host brain. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and Western blot were used to detect the apoptosis and expression of BAX and BAD. RESULTS: Microarray analysis showed that BMSCs expressed growth factors such as glial cell-line derived neurotrophic factor (GDNF). The cells migrated around the injury sites in rats with TBI. BMSC grafts resulted in an increased number of GAP-43-immunopositive fibers and synaptophysin-positive varicosity, with suppressed apoptosis. Furthermore, BMSC transplantation significantly downregulated the expression of BAX and BAD signaling. Moreover, cultured BMSC transplantation significantly improved rat neurological function and survival. CONCLUSION: Transplanted BMSCs could survive and improve neuronal behavior in rats with TBI. Mechanisms of neuroprotection and regeneration were involved, which could be associated with the GDNF regulating the apoptosis signals through BAX and BAD. PMID- 26871687 TI - Assessment of Cervicovaginal Cancer Antigen 125 Levels: A Preliminary Study for Endometrial Cancer Screening. AB - AIM: We primarily aimed to compare the levels of serum and cervicovaginal cancer antigen 125 (CA 125) in women with and without endometrial carcinoma in order to reveal whether cervicovaginal CA 125 could be used as a non-invasive method. METHODS: A preliminary case-control study was designed. The study group consisted of patients who were operated for endometrial adenocarcinoma or endometrial intraepithelial neoplasia. The control group consisted of patients who underwent surgery for benign gynecological diseases. Serum and cervicovaginal secretions were immediately collected before surgery to compare levels of CA 125. RESULTS: The mean cervicovaginal CA 125 levels in patients with endometrial cancer and controls were 1,598.1 +/- 1,691.1 versus 947.0 +/- 1,282.7 U/ml, respectively (p = 0.016). Whereas area under receiver operating characteristic curve was 0.62 for serum CA 125, it was 0.68 for cervicovaginal CA 125. The optimal threshold of CA 125 in cervicovaginal secretion was calculated to be 575 U/ml, which detected endometrial precancer or cancer with sensitivity of 78% and specificity of 57%. The positive and negative predictive values for this threshold were 38.7 and 88.2%, respectively. CONCLUSION: In conclusion, detection of CA 125 in cervicovaginal secretion has a potential role for the non-invasive screening of endometrial precancers and cancers. PMID- 26871688 TI - Acute Ischemia of the Glans Penis after Circumcision Treated with Hyperbaric Therapy and Pentoxifylline: Case Report and Revision of the Literature. AB - Acute severe ischemia of glans penis after circumcision is a very rare event and, if not treated, can lead to irreversible necrosis with severe consequences such as loss of part of the penis. The possible causes for this condition could be blood-vessel binding or cauterization, dorsal penile nerve block (DPNB), local anesthesia with vasoconstricting agents and wound dressing compression. The aim of the treatment is to provide good blood supply and thus, oxygen delivery to the ischemic penis. The therapeutic options include hyperbaric therapy (HBOT), pentoxifylline (PTX), enoxaparina, iloprost, antiplatelet, corticosteroids and peridural anesthesia. We report the case of a 24-year-old male who developed an acute severe glans penis ischemia after circumcision done under DPNB. The patient was successfully treated with HBOT in combination with PTX. PMID- 26871692 TI - Effects of neuromuscular electrical stimulation and low-level laser therapy on neuromuscular parameters and health status in elderly women with knee osteoarthritis: A randomized trial. AB - OBJECTIVE: To determine the effects of neuromuscular electrical stimulation and low-level laser therapy on neuromuscular parameters and health status in elderly subjects with knee osteoarthritis. DESIGN: A randomized evaluator-blinded clinical trial. SUBJECTS: Forty-five elderly women with knee osteoarthritis. METHODS: Subjects were randomized into 1 of the following 3 intervention groups: electrical stimulation group (18-32 min pulsed current, stimulation frequency 80 Hz, pulse duration 400 MUs, stimulation intensity 40% of maximal isometric voluntary contraction), laser group (dose 4-6 J per point, 6 points at the knee joint) or combined group (electrical stimulation plus laser therapy). The outcomes included muscle thickness and anatomical cross-sectional area (ultrasonography), knee extensors' electrical activity (electromyography), torque (dynamometry) and health status (Western Ontario and McMaster Universities Osteoarthritis Index). All groups underwent a 4-week control period (without intervention) followed by an 8-week intervention period. RESULTS: Muscle thickness and anatomical cross-sectional area increased in the electrical stimulation and combined groups. All groups presented similar improvements in torque, electrical activity and health status. CONCLUSION: Electrical stimulation alone or in combination with laser therapy generated positive effects on all evaluated parameters. Laser therapy increased health status and electrical activity, but had no effect on muscle mass. PMID- 26871689 TI - Epidemiology, Impact and Control of Rabies in Nepal: A Systematic Review. AB - BACKGROUND: Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal. METHODS: We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal. FINDINGS: So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10-100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle. INTERPRETATION: Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal. PMID- 26871693 TI - Aquaporin-1 Expression in Retinal Pigment Epithelial Cells Overlying Retinal Drusen. AB - PURPOSE: In the outer retina, age-related macular degeneration (AMD) results in reduced hydraulic conductivity in Bruch's membrane, possibly leading to altered water transport in retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may express aquaporin-1 (AQP1) to compensate for these changes. Therefore, we wanted to investigate the expression of AQP1 in RPE cells of human eyes with age-related maculopathy (ARM) and AMD, and eyes with tumour-associated drusen. METHODS: Nine human eyes with ARM, 6 eyes with AMD and 9 eyes with choroidal malignant melanoma were examined for immunoreactivity to AQP1. AQP1 labelling in the RPE cells was evaluated for each drusen and grouped according to size and AQP1 labelling. AQP1 labelling in the RPE outside drusen was also evaluated. RESULTS: AQP1 labelling was observed in the apical membrane of the RPE cells situated above drusen in all three groups. There was a significant association between AQP1 labelling and drusen size (p < 0.001), and AQP1 labelling was more frequently observed in large drusen. CONCLUSION: AQP1 was expressed in RPE cells covering drusen but not in RPE cells outside drusen. We suggest that AQP1 expression is upregulated in the cell membranes of RPE cells above drusen in order to alleviate the increased need for fluid transport across the growing drusen. PMID- 26871690 TI - Effect of Dietary Restriction and Subsequent Re-Alimentation on the Transcriptional Profile of Bovine Skeletal Muscle. AB - Compensatory growth (CG), an accelerated growth phenomenon which occurs following a period of dietary restriction is exploited worldwide in animal production systems as a method to lower feed costs. However the molecular mechanisms regulated CG expression remain to be elucidated fully. This study aimed to uncover the underlying biology regulating CG in cattle, through an examination of skeletal muscle transcriptional profiles utilising next generation mRNA sequencing technology. Twenty Holstein Friesian bulls were fed either a restricted diet for 125 days, with a target growth rate of 0.6 kg/day (Period 1), following which they were allowed feed ad libitum for a further 55 days (Period 2) or fed ad libitum for the entirety of the trial. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2 respectively and RNAseq analysis was performed. During re-alimentation in Period 2, previously restricted animals displayed CG, growing at 1.8 times the rate of the ad libitum control animals. Compensating animals were also more feed efficient during re alimentation and compensated for 48% of their previous dietary restriction. 1,430 and 940 genes were identified as significantly differentially expressed (Benjamini Hochberg adjusted P < 0.1) in periods 1 and 2 respectively. Additionally, 2,237 genes were differentially expressed in animals undergoing CG relative to dietary restriction. Dietary restriction in Period 1 was associated with altered expression of genes involved in lipid metabolism and energy production. CG expression in Period 2 occurred in association with greater expression of genes involved in cellular function and organisation. This study highlights some of the molecular mechanisms regulating CG in cattle. Differentially expressed genes identified are potential candidate genes for the identification of biomarkers for CG and feed efficiency, which may be incorporated into future breeding programmes. PMID- 26871694 TI - Ranking of Business Process Simulation Software Tools with DEX/QQ Hierarchical Decision Model. AB - The omnipresent need for optimisation requires constant improvements of companies' business processes (BPs). Minimising the risk of inappropriate BP being implemented is usually performed by simulating the newly developed BP under various initial conditions and "what-if" scenarios. An effectual business process simulations software (BPSS) is a prerequisite for accurate analysis of an BP. Characterisation of an BPSS tool is a challenging task due to the complex selection criteria that includes quality of visual aspects, simulation capabilities, statistical facilities, quality reporting etc. Under such circumstances, making an optimal decision is challenging. Therefore, various decision support models are employed aiding the BPSS tool selection. The currently established decision support models are either proprietary or comprise only a limited subset of criteria, which affects their accuracy. Addressing this issue, this paper proposes a new hierarchical decision support model for ranking of BPSS based on their technical characteristics by employing DEX and qualitative to quantitative (QQ) methodology. Consequently, the decision expert feeds the required information in a systematic and user friendly manner. There are three significant contributions of the proposed approach. Firstly, the proposed hierarchical model is easily extendible for adding new criteria in the hierarchical structure. Secondly, a fully operational decision support system (DSS) tool that implements the proposed hierarchical model is presented. Finally, the effectiveness of the proposed hierarchical model is assessed by comparing the resulting rankings of BPSS with respect to currently available results. PMID- 26871696 TI - Arterial Spin Labeling Perfusion Study in the Patients with Subacute Mild Traumatic Brain Injury. AB - BACKGROUND: This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient's cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits. OBJECTIVE: To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients. METHODS: After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients. RESULT: We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes. CONCLUSION: First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms. PMID- 26871697 TI - A Population-Based Cohort Study on Peripheral Arterial Disease in Patients with Schizophrenia. AB - PURPOSE: Peripheral arterial disease (PAD) is considered the leading cause of atherosclerotic cardiovascular morbidity. Several risk factors of PAD have been observed in patients with schizophrenia. Therefore, we hypothesize that the incidence of PAD is higher in the schizophrenia population than in the general population. METHODS: The patients in this population-based cohort study were selected from the Taiwanese National Health Insurance Research Database on the basis of the claims data from 2000 to 2011. We compared the incidence of PAD between schizophrenia and nonschizophrenia cohorts. Cox proportional hazard regression models were employed for analyzing the risk of PAD after adjustment for sex, age, and comorbidities. RESULTS: The adjusted hazard ratio (HR) for PAD in the schizophrenia cohort was 1.26-fold higher than that in the nonschizophrenia cohort. Furthermore, patients with schizophrenia using atypical antipsychotics exhibited a high adjusted HR for PAD. CONCLUSION: Compared with the general population, the risk of PAD is higher among patients with schizophrenia. Early diagnosis and intervention can mitigate complications resulting from cardiovascular diseases and lower mortality. PMID- 26871695 TI - Sex Differences in Circadian Dysfunction in the BACHD Mouse Model of Huntington's Disease. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies indicate there may be sex differences in disease progression. One of the early symptoms of HD is disruptions in the circadian timing system, but it is currently unknown whether sex is a factor in these alterations. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s) and designing early intervention strategies, we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in circadian behavioral rhythms are detectable in an animal model of the disease. Similar to BACHD males, BACHD females display circadian disruptions at both 3 and 6 months of age; however, deficits to BACHD female mouse activity levels, rhythm precision, and behavioral fragmentation are either delayed or less severe relative to males. These sex differences are associated with a smaller suprachiasmatic nucleus (SCN) in BACHD male mice at age of symptom onset (3 months), but are not associated with sex-specific differences in SCN daytime electrical activity deficits, or peptide expression (arginine vasopressin, vasoactive intestinal peptide) within the SCN. Notably, BACHD females exhibited delayed motor coordination deficits, as measured using rotarod and challenge beam. These findings suggest a sex specific factor plays a role both in non-motor and motor symptom progression for the BACHD mouse. PMID- 26871698 TI - Aluminium Accumulation and Intra-Tree Distribution Patterns in Three Arbor aluminosa (Symplocos) Species from Central Sulawesi. AB - Accumulation of Aluminium (Al) at concentrations far above 1,000 mg kg-1 in aboveground plant tissues of Arbor aluminosa (Symplocos) species is the main reason why traditional Indonesian weavers rely on their leaves and bark as a mordant for dyeing textile. Recently, Symplocos species have become a flagship species for the conservation efforts of weaving communities due to their traditionally non-sustainable sampling and increasing demand for Symplocos plant material. Here we investigated Symplocos odoratissima, S. ophirensis and S. ambangensis at three montane rainforest sites in Central Sulawesi to measure Al levels in different tissues and organs. The highest Al concentrations were found in old leaves (24,180 +/- 7,236 mg.kg-1 dry weight, mean +/- SD), while young leaves had significantly lower Al levels (20,708 +/- 7,025 mg.kg-1). Al accumulation was also lower in bark and wood tissue of the trunk (17,231 +/- 8,356 mg.kg-1 and 5,181 +/- 2,032 mg.kg-1, respectively). Two Al excluding species (Syzigium sp. and Lithocarpus sp.) contained only high Al levels in their roots. Moreover, no difference was found in soil pH (4.7 +/- 0.61) and nutrient (K, Ca, Fe, Mg) availability at different soil levels and within or outside the crown of Symplocos trees, except for the upper soil layer. Furthermore, a positive and significant correlation between Al and Ca concentrations was found at the whole plant level for Symplocos, and at the leaf level for S. ophirensis and S. ambangensis, suggesting a potential role of Ca in Al uptake and/or detoxification within the plant. Our results provide evidence for strong Al accumulation in Symplocos species and illustrate that both Al accumulation and exclusion represent two co-occurring strategies of montane rainforest plants for dealing with Al toxicity. Indonesian weavers should be encouraged to harvest old leaves, which have the most efficient mordant capacity due to high Al concentrations. PMID- 26871699 TI - Debriefing as an Essential Part of Keeping Ourselves Healthy. PMID- 26871700 TI - Diabetic Macular Edema at the time of Cataract Surgery trial: a prospective, randomized clinical trial of intravitreous bevacizumab versus triamcinolone in patients with diabetic macular oedema at the time of cataract surgery - preliminary 6 month results. AB - BACKGROUND: To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME). DESIGN: Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne. PARTICIPANTS: Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months. METHODS: Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months. MAIN OUTCOME MEASURES: Change in central macular thickness (CMT) and best corrected visual acuity at 6 months. RESULTS: Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of >=6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (-43.8-um reduction TA vs. +37.3-um increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up; BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group. CONCLUSIONS: When administered at the time of cataract surgery in patients with DME, at 6 months both TA and BVB improve visual acuity; however, only TA results in a sustained reduction in CMT. Further follow-up will determine whether this translates into better long-term visual outcomes in the TA group. PMID- 26871702 TI - A different kind of case report: II. PMID- 26871701 TI - A Fine Balance of Synaptophysin Levels Underlies Efficient Retrieval of Synaptobrevin II to Synaptic Vesicles. AB - Synaptobrevin II (sybII) is a vesicular soluble NSF attachment protein receptor (SNARE) protein that is essential for neurotransmitter release, and thus its correct trafficking to synaptic vesicles (SVs) is critical to render them fusion competent. The SV protein synaptophysin binds to sybII and facilitates its retrieval to SVs during endocytosis. Synaptophysin and sybII are the two most abundant proteins on SVs, being present in a 1:2 ratio. Synaptophysin and sybII are proposed to form a large multimeric complex, and the copy number of the proteins in this complex is also in a 1:2 ratio. We investigated the importance of this ratio between these proteins for the localisation and trafficking of sybII in central neurons. SybII was overexpressed in mouse hippocampal neurons at either 1.6 or 2.15-2.35-fold over endogenous protein levels, in the absence or presence of varying levels of synaptophysin. In the absence of exogenous synaptophysin, exogenous sybII was dispersed along the axon, trapped on the plasma membrane and retrieved slowly during endocytosis. Co-expression of exogenous synaptophysin rescued all of these defects. Importantly, the expression of synaptophysin at nerve terminals in a 1:2 ratio with sybII was sufficient to fully rescue normal sybII trafficking. These results demonstrate that the balance between synaptophysin and sybII levels is critical for the correct targeting of sybII to SVs and suggests that small alterations in synaptophysin levels might affect the localisation of sybII and subsequent presynaptic performance. PMID- 26871703 TI - Assessing Disease and Mortality among Small Cetaceans Stranded at a World Heritage Site in Southern Brazil. AB - Cetaceans are considered environmental sentinels and their health often reflects either anthropogenic or natural spatio-temporal disturbances. This study investigated the pathological findings and mortality of small cetaceans with the aim of detecting hazards and monitoring health trends in a high-biodiversity area. Between 2007 and 2012, 218 stranded cetaceans were recorded on the Parana coast, southern Brazil. Fifty-seven (26.1%) of these animals, including 50 Sotalia guianensis, 2 Pontoporia blainvillei, 2 Stenella frontalis, 1 Stenella longirostris, 1 Tursiops truncatus and 1 Globicephala melas were necropsied and samples were collected for histopathology. Causes of death were determined in 46 of the 57 (80.7%) animals and most (30 or 65.2%) were ascribed to anthropogenic activities, including fisheries bycatch (28/30) and trauma (2/30). The remaining 16 fatalities were considered natural, and attributed to pneumonia (10/16), emaciation (3/16), septicemia (1/16), neonatal pathology (1/16) and choking via food obstruction (1/16). Irrespective of the cause, bronchointerstitial pneumonia, associated with parasitism, lymphadenitis and membranous glomerulonephritis were common findings among all fatalities. These results suggest, that while anthropogenic activities are a leading cause of cetacean strandings in Parana, underlying pre-existing diseases may contribute towards deaths. Although the studied area is considered a biosphere reserve by UNESCO, complex anthropogenic and natural interactions might be occurring, increasing cetacean susceptibility to hazards. This study may help facilitate developing an effective conservation plan for coastal cetaceans focusing on reducing fisheries interactions, habitat degradation and pollution as mechanisms for ultimately increasing species resilience. PMID- 26871704 TI - Implementation of an Interdisciplinary, Team-Based Complex Care Support Health Care Model at an Academic Medical Center: Impact on Health Care Utilization and Quality of Life. AB - INTRODUCTION: The Geriatric Resources for the Assessment and Care of Elders (GRACE) program has been shown to decrease acute care utilization and increase patient self-rated health in low-income seniors at community-based health centers. AIMS: To describe adaptation of the GRACE model to include adults of all ages (named Care Support) and to evaluate the process and impact of Care Support implementation at an urban academic medical center. SETTING: 152 high-risk patients (>=5 ED visits or >=2 hospitalizations in the past 12 months) enrolled from four medical clinics from 4/29/2013 to 5/31/2014. PROGRAM DESCRIPTION: Patients received a comprehensive in-home assessment by a nurse practitioner/social worker (NP/SW) team, who then met with a larger interdisciplinary team to develop an individualized care plan. In consultation with the primary care team, standardized care protocols were activated to address relevant key issues as needed. PROGRAM EVALUATION: A process evaluation based on the Consolidated Framework for Implementation Research identified key adaptations of the original model, which included streamlining of standardized protocols, augmenting mental health interventions and performing some assessments in the clinic. A summative evaluation found a significant decline in the median number of ED visits (5.5 to 0, p = 0.015) and hospitalizations (5.5 to 0, p<0.001) 6 months before enrollment in Care Support compared to 6 months after enrollment. In addition, the percent of patients reporting better self-rated health increased from 31% at enrollment to 64% at 9 months (p = 0.002). Semi-structured interviews with Care Support team members identified patients with multiple, complex conditions; little community support; and mild anxiety as those who appeared to benefit the most from the program. DISCUSSION: It was feasible to implement GRACE/Care Support at an academic medical center by making adaptations based on local needs. Care Support patients experienced significant reductions in acute care utilization and significant improvements in self-rated health. PMID- 26871705 TI - MicroRNAs Are Involved in the Regulation of Ovary Development in the Pathogenic Blood Fluke Schistosoma japonicum. AB - Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production. PMID- 26871708 TI - Correction: Strong Associations Exist among Oxidative Stress and Antioxidant Biomarkers in the Circulating, Cellular and Urinary Anatomical Compartments in Guatemalan Children from the Western Highlands. PMID- 26871707 TI - Heat and PAHs Emissions in Indoor Kitchen Air and Its Impact on Kidney Dysfunctions among Kitchen Workers in Lucknow, North India. AB - Indoor air quality and heat exposure have become an important occupational health and safety concern in several workplaces including kitchens of hotels. This study investigated the heat, particulate matter (PM), total volatile organic compounds (TVOCs) and polycyclic aromatic hydrocarbons (PAHs) emissions in indoor air of commercial kitchen and its association with kidney dysfunctions among kitchen workers. A cross sectional study was conducted on 94 kitchen workers employed at commercial kitchen in Lucknow city, North India. A questionnaire-based survey was conducted to collect the personal and occupational history of the kitchen workers. The urine analysis for specific gravity and microalbuminuria was conducted among the study subjects. Indoor air temperature, humidity, wet/ dry bulb temperature and humidex heat stress was monitored during cooking activities at the kitchen. Particulate matter (PM) for 1 and 2.5 microns were monitored in kitchen during working hours using Hazdust. PAHS in indoor air was analysed using UHPLC. Urinary hydroxy-PAHs in kitchen workers were measured using GC/MS-MS. Higher indoor air temperature, relative humidity, PM1 and PM2.5 (p<0.001) was observed in the kitchen due to cooking process. Indoor air PAHs identified are Napthalene, fluorine, acenaphthene, phenanthrene, pyrene, chrysene and indeno [1,2,3-cd) pyrene. Concentrations of all PAHs identified in kitchen were above the permissible OSHA norms for indoor air. Specific gravity of urine was significantly higher among the kitchen workers (p<0.001) as compared to the control group. Also, the prevalence of microalbuminuria was higher (p<0.001) among kitchen workers. Urinary PAH metabolites detected among kitchen workers were 1-NAP, 9-HF, 3-HF, 9-PHN and 1-OHP. Continuous heat exposure in kitchens due to cooking can alter kidney functions viz., high specific gravity of urine in kitchen workers. Exposure to PM, VOCs and PAHs in indoor air and presence of urinary PAHs metabolites may lead to inflammation, which can cause microalbuminuria in kitchen workers, as observed in the present study. PMID- 26871710 TI - An overview of burning mouth syndrome for the dermatologist. AB - Burning mouth syndrome is characterized by an idiopathic burning pain affecting the oral mucosa, with no clinically apparent changes. It can present to a variety of health professionals including dermatologists. This article summarizes the important aspects of the condition, including theories of pathogenesis, diagnosis and management. PMID- 26871706 TI - Developing a Physiologically-Based Pharmacokinetic Model Knowledgebase in Support of Provisional Model Construction. AB - Developing physiologically-based pharmacokinetic (PBPK) models for chemicals can be resource-intensive, as neither chemical-specific parameters nor in vivo pharmacokinetic data are easily available for model construction. Previously developed, well-parameterized, and thoroughly-vetted models can be a great resource for the construction of models pertaining to new chemicals. A PBPK knowledgebase was compiled and developed from existing PBPK-related articles and used to develop new models. From 2,039 PBPK-related articles published between 1977 and 2013, 307 unique chemicals were identified for use as the basis of our knowledgebase. Keywords related to species, gender, developmental stages, and organs were analyzed from the articles within the PBPK knowledgebase. A correlation matrix of the 307 chemicals in the PBPK knowledgebase was calculated based on pharmacokinetic-relevant molecular descriptors. Chemicals in the PBPK knowledgebase were ranked based on their correlation toward ethylbenzene and gefitinib. Next, multiple chemicals were selected to represent exact matches, close analogues, or non-analogues of the target case study chemicals. Parameters, equations, or experimental data relevant to existing models for these chemicals and their analogues were used to construct new models, and model predictions were compared to observed values. This compiled knowledgebase provides a chemical structure-based approach for identifying PBPK models relevant to other chemical entities. Using suitable correlation metrics, we demonstrated that models of chemical analogues in the PBPK knowledgebase can guide the construction of PBPK models for other chemicals. PMID- 26871709 TI - The Impact of HIV Co-Infection on the Genomic Response to Sepsis. AB - HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID- 26871711 TI - Body mass index curves for Italian preterm infants are comparable with American curves for infants born before 34 weeks of gestational age. AB - AIM: Body mass index (BMI)-for-age curves have been developed in the USA, but not compared with other populations. This study created gender-specific intrauterine BMI-for-age curves for Italian preterm infants and compared them with the USA version. METHODS: Data on 92 262 newborn infants, born at 26-42 weeks of gestational age in the north-eastern Italian region of Friuli Venezia Giulia between 2005 and 2013, were analysed to create gender-specific BMI-for-age curves. Gender-specific and age-specific BMI Z scores for Italian infants were calculated using the parameters of the USA growth curves and the World Health Organization charts. RESULTS: Gender-specific BMI-for-age at birth curves were developed for premature Italian infants from 26 gestational weeks. The comparison with the USA charts showed no significant difference in BMI percentiles in Italian infants born at <=33 gestational weeks, but infants born at >=34 gestational weeks had a significantly higher BMI than the USA population, by 0.2 standard deviations. CONCLUSION: We developed the first European BMI-for-age at birth curves for premature infants. According to our findings, the Italian curves were comparable to the USA curves for the subgroup of infants born at <=33 gestational weeks, but not >=34 gestational weeks. PMID- 26871712 TI - Impact of Reducing Complement Inhibitor Binding on the Immunogenicity of Native Neisseria meningitidis Outer Membrane Vesicles. AB - Neisseria meningitidis recruits host human complement inhibitors to its surface to down-regulate complement activation and enhance survival in blood. We have investigated whether such complement inhibitor binding occurs after vaccination with native outer membrane vesicles (nOMVs), and limits immunogenicity of such vaccines. To this end, nOMVs reactogenic lipopolysaccharide was detoxified by deletion of the lpxl1 gene (nOMVlpxl1). nOMVs unable to bind human complement factor H (hfH) were generated by additional deletions of the genes encoding factor H binding protein (fHbp) and neisserial surface protein A (NspA) (nOMVdis). Antibody responses elicited in mice with nOMVdis were compared to those elicited with nOMVlpxl1 in the presence of hfH. Results demonstrate that the administration of human fH to mice immunized with fHbp containing OMVlpxl1 decreased immunogenicity against fHbp (but not against the OMV as a whole). The majority of the OMV-induced bactericidal immune response (OMVlpxl1 or OMVdis) was versus PorA. Despite a considerable reduction of hfH binding to nOMVdis, and the absence of the vaccine antigen fHbp, immunogenicity in mice was not different from nOMVlpxl1, in the absence or presence of hfH (serum bactericidal titers of 1:64 vs 1:128 after one dose in the nOMVdis and nOMVlpxl1-immunized groups respectively). Therefore, partial inhibition of fH binding did not enhance immunity in this model. PMID- 26871713 TI - The prognostic value of interim and end-of-treatment PET/CT in patients with newly diagnosed peripheral T-cell lymphoma. PMID- 26871714 TI - Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly diagnosed, previously untreated multiple myeloma: an open-label phase I trial. AB - The safety and efficacy of siltuximab (CNTO 328) was tested in combination with lenalidomide, bortezomib and dexamethasone (RVD) in patients with newly diagnosed, previously untreated symptomatic multiple myeloma. Fourteen patients were enrolled in the study, eleven of whom qualified to receive therapy. A majority of patients (81.8%) completed the minimal number or more of the four required cycles, while two patients completed only three cycles. The maximum tolerated dose (MTD) of siltuximab with RVD was dose level -1 (siltuximab: 8.3 mg/kg; bortezomib: 1.3 mg/m(2); lenalidomide: 25 mg; dexamethasone: 20 mg). Serious adverse events were grade 3 pneumonia and grade 4 thrombocytopenia, and no deaths occurred during the study or with follow-up (median follow-up 28.1 months). An overall response rate, after 3-4 cycles of therapy, of 90.9% (95% confidence interval (CI): 58.7%, 99.8%) (9.1% complete response (95% CI: 0.2%, 41.3%), 45.5% very good partial response (95% CI: 16.7%, 76.6%) and 36.4% partial response (95% CI: 10.9%, 69.2%)) was seen. Two patients withdrew consent, and nine patients (81.8%) opted for autologous stem cell transplantation. PMID- 26871716 TI - Time to manage: patient strategies for coping with an absence of care coordination and continuity. AB - This paper examines how people with chronic illnesses respond to absences of continuity and coordination of care. Little work has been done on how the ill person might mitigate flaws in a less than optimal system. Our qualitative research, carried out among 91 participants in Australia, reveals that people with chronic illnesses create strategies to facilitate the management of their care. These strategies included efforts to improve communication between themselves and their health care practitioners; keeping personal up-to-date medication lists; and generating their own specific management plans. While we do not submit that it is patients' responsibility to attend to gaps in the health system, our data suggests that chronically ill people can, in and through such strategies, exert a measure of agency over their own care; making it effectively more continuous and coordinated. Participants crafted strategies according to the particular social and bodily rhythms that their ongoing illnesses had lent to their lives. Our analysis advances the view that the ill body itself is capable of enfolding the health system into the rhythms of illness - rather than the ill body always fitting into the overarching structural tempo. This entails an agent centric view of time in illness experience. A Virtual Abstract of this paper can be found at: https://youtu.be/UwbxlEJOTx8. PMID- 26871715 TI - A Signal Processing Approach for Detection of Hemodynamic Instability before Decompensation. AB - Advanced hemodynamic monitoring is a critical component of treatment in clinical situations where aggressive yet guided hemodynamic interventions are required in order to stabilize the patient and optimize outcomes. While there are many tools at a physician's disposal to monitor patients in a hospital setting, the reality is that none of these tools allow hi-fidelity assessment or continuous monitoring towards early detection of hemodynamic instability. We present an advanced automated analytical system which would act as a continuous monitoring and early warning mechanism that can indicate pending decompensation before traditional metrics can identify any clinical abnormality. This system computes novel features or bio-markers from both heart rate variability (HRV) as well as the morphology of the electrocardiogram (ECG). To compare their effectiveness, these features are compared with the standard HRV based bio-markers which are commonly used for hemodynamic assessment. This study utilized a unique database containing ECG waveforms from healthy volunteer subjects who underwent simulated hypovolemia under controlled experimental settings. A support vector machine was utilized to develop a model which predicts the stability or instability of the subjects. Results showed that the proposed novel set of features outperforms the traditional HRV features in predicting hemodynamic instability. PMID- 26871717 TI - No Negative Impact of Palliative Sedation on Relatives' Experience of the Dying Phase and Their Wellbeing after the Patient's Death: An Observational Study. AB - BACKGROUND: Palliative sedation is the widely-used intervention of administering sedating agents to induce a state of unconsciousness to take away a dying patient's perception of otherwise irrelievable symptoms. However, it remains questionable whether this ethically complex intervention is beneficial for patients and whether the associated lack of communication in the last phase of life has a negative impact on relatives' wellbeing. METHODS: An observational questionnaire study was conducted among relatives of a consecutive sample of patients who died a non-sudden death in the Erasmus MC Cancer Institute or in the hospice 'Laurens Cadenza' (both in Rotterdam) between 2010 and 2013. RESULTS: Relatives filled in questionnaires regarding 151 patients who had been sedated and 90 patients who had not been sedated. The median time since all patients had passed away was 21 (IQR 14-32) months. No significant differences were found in relatives' assessments of the quality of end-of-life care, patients' quality of life in the last week before death and their quality of dying, between patients who did and did not receive sedation, or in relatives' satisfaction with their own life, their general health and their mental wellbeing after the patient's death. CONCLUSIONS: The use of sedation in these patients appears to have no negative effect on bereaved relatives' evaluation of the patient's dying phase, or on their own wellbeing after the patient's death. PMID- 26871718 TI - Structure-Based Design of Peptidic Inhibitors of the Interaction between CC Chemokine Ligand 5 (CCL5) and Human Neutrophil Peptides 1 (HNP1). AB - Protein-protein interactions (PPIs) are receiving increasing interest, much sparked by the realization that they represent druggable targets. Recently, we successfully developed a peptidic inhibitor, RRYGTSKYQ ("SKY" peptide), that shows high potential in vitro and in vivo to interrupt a PPI between the platelet borne chemokine CCL5 and the neutrophil-derived granule protein HNP1. This PPI plays a vital role in monocyte adhesion, representing a key mechanism in acute and chronic inflammatory diseases. Here, we present extensive and detailed computational methods applied to develop the SKY peptide. We combined experimentally determined binding affinities (KD) of several orthologs of CCL5 with HNP1 with in silico studies to identify the most likely heterodimeric CCL5 HNP1 complex which was subsequently used as a starting structure to rationally design peptidic inhibitors. Our method represents a fast and simple approach that can be widely applied to determine other protein-protein complexes and moreover to design inhibitors or stabilizers of protein-protein interaction. PMID- 26871719 TI - Reduction of Genetic Diversity of the Harpy Eagle in Brazilian Tropical Forests. AB - Habitat loss and fragmentation intensify the effects of genetic drift and endogamy, reducing genetic variability of populations with serious consequences for wildlife conservation. The Harpy Eagle (Harpia harpyja) is a forest dwelling species that is considered near threatened and suffers from habitat loss in the forests of the Neotropical region. In this study, 72 historical and current samples were assessed using eight autosomal microsatellite markers to investigate the distribution of genetic diversity of the Harpy Eagle of the Amazonian and Atlantic forests in Brazil. The results showed that the genetic diversity of Harpy Eagle decreased in the regions where deforestation is intense in the southern Amazon and Atlantic Forest. PMID- 26871721 TI - Structural Evolution and Electronic Properties of VnC2(0/-) and VnC4(0/-) (n = 1 6) Clusters: Insights from Photoelectron Spectroscopy and Theoretical Calculations. AB - The structural evolution and electronic properties of VnC2(-/0) and VnC4(-/0) (n = 1-6) clusters were investigated using photoelectron spectroscopy and density functional theory calculations. The adiabatic and vertical detachment energies of VnC2(-) and VnC4(-) (n = 1-6) clusters were obtained from their photoelectron spectra. The most stable structures were identified by comparing the results of our calculations with the experimental data. We found that the carbon atoms of VnC2(-/0) and VnC4(-/0) (n = 1-6) clusters were separated gradually with increasing number of vanadium atoms. For VnC2(-/0) (n = 3-6) and VnC4(-/0) (n = 4 6) clusters, the carbon atoms are separated by the vanadium atoms. The geometry of V4C4 is a cubic structure and the geometries of V5C4 and V6C4 are formed by one and two vanadium atoms capping the cubic V4C4 structure, respectively. PMID- 26871720 TI - Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility. AB - Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker. PMID- 26871722 TI - Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2. AB - Somatic mutations of the cohesin complex subunit STAG2 are present in diverse tumor types. We and others have shown that STAG2 inactivation can lead to loss of sister chromatid cohesion and alterations in chromosome copy number in experimental systems. However, studies of naturally occurring human tumors have demonstrated little, if any, correlation between STAG2 mutational status and aneuploidy, and have further shown that STAG2-deficient tumors are often euploid. In an effort to provide insight into these discrepancies, here we analyze the effect of tumor-derived STAG2 mutations on the protein composition of cohesin and the expected mitotic phenotypes of STAG2 mutation. We find that many mutant STAG2 proteins retain their ability to interact with cohesin; however, the presence of mutant STAG2 resulted in a reduction in the ability of regulatory subunits WAPL, PDS5A, and PDS5B to interact with the core cohesin ring. Using AAV-mediated gene targeting, we then introduced nine tumor-derived mutations into the endogenous allele of STAG2 in cultured human cells. While all nonsense mutations led to defects in sister chromatid cohesion and a subset induced anaphase defects, missense mutations behaved like wild-type in these assays. Furthermore, only one of nine tumor-derived mutations tested induced overt alterations in chromosome counts. These data indicate that not all tumor-derived STAG2 mutations confer defects in cohesion, chromosome segregation, and ploidy, suggesting that there are likely to be other functional effects of STAG2 inactivation in human cancer cells that are relevant to cancer pathogenesis. PMID- 26871723 TI - Genome-Wide Diversity and Phylogeography of Mycobacterium avium subsp. paratuberculosis in Canadian Dairy Cattle. AB - Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne's disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six "Bison type" isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Quebec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale. PMID- 26871725 TI - The Incidence of Abortion in Nigeria. AB - CONTEXT: Because of Nigeria's low contraceptive prevalence, a substantial number of women have unintended pregnancies, many of which are resolved through clandestine abortion, despite the country's restrictive abortion law. Up-to-date estimates of abortion incidence are needed. METHODS: A widely used indirect methodology was used to estimate the incidence of abortion and unintended pregnancy in Nigeria in 2012. Data on provision of abortion and postabortion care were collected from a nationally representative sample of 772 health facilities, and estimates of the likelihood that women who have unsafe abortions experience complications and obtain treatment were collected from 194 health care professionals with a broad understanding of the abortion context in Nigeria. RESULTS: An estimated 1.25 million induced abortions occurred in Nigeria in 2012, equivalent to a rate of 33 abortions per 1,000 women aged 15-49. The estimated unintended pregnancy rate was 59 per 1,000 women aged 15-49. Fifty-six percent of unintended pregnancies were resolved by abortion. About 212,000 women were treated for complications of unsafe abortion, representing a treatment rate of 5.6 per 1,000 women of reproductive age, and an additional 285,000 experienced serious health consequences but did not receive the treatment they needed. CONCLUSION: Levels of unintended pregnancy and unsafe abortion continue to be high in Nigeria. Improvements in access to contraceptive services and in the provision of safe abortion and postabortion care services (as permitted by law) may help reduce maternal morbidity and mortality. PMID- 26871726 TI - Understanding the Broader Sexual and Reproductive Health Needs of Female Sex Workers in Dhaka, Bangladesh. AB - CONTEXT: Little is known about the sexual and reproductive health care needs of female sex workers in Dhaka, Bangladesh. METHODS: Survey data were collected from 354 hotel-based and 323 street-based female sex workers using a venue-based stratified cluster sampling approach. In addition, in-depth interviews were conducted with 20 female sex workers recruited from drop-in centers. We calculated unmet need for family planning and examined fertility desires, use of condoms and other contraceptive methods, experiences with gender-based violence, sexual and reproductive health service needs, and preferences on where to receive services. RESULTS: The prevalence of unmet need was 25% among hotel-based female sex workers and 36% among street-based female sex workers. Almost all participants reported having used condoms in the past 30 days, and 44% of hotel based sex workers and 30% of street-based sex workers reported dual method use during that period. Condom use was inconsistent, however, and condom breakage and nonuse for extra money were common. Many women reported experiencing gender-based violence. Sexual and reproductive health services had been obtained by 64% of hotel-based and 89% of street-based sex workers in the past six months; drop-in centers were their preferred site for receiving health services. CONCLUSIONS: Female sex workers in Dhaka need family planning and other sexual and reproductive health services and prefer receiving them from drop-in centers. PMID- 26871724 TI - Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension. AB - We previously reported that 15-lipoxygenase (15-LO) and its metabolite 15 hydroxyeicosatetraenoic acid (15-HETE) were up-regulated in pulmonary arterial cells from both pulmonary artery hypertension patients and hypoxic rats and that these factors mediated the progression of pulmonary hypertension (PH) by affecting the proliferation and apoptosis of pulmonary arterial (PA) cells. However, the underlying mechanisms of the remodeling induced by 15-HETE have remained unclear. As reactive oxygen species (ROS) and 15-LO are both induced by hypoxia, it is possible that ROS are involved in the events of hypoxia-induced 15 LO expression that lead to PH. We employed immunohistochemistry, tube formation assays, bromodeoxyuridine (BrdU) incorporation assays, and cell cycle analyses to explore the role of ROS in the process of 15-HETE-mediated hypoxic pulmonary hypertension (HPH). We found that exogenous 15-HETE facilitated the generation of ROS and that this effect was mainly localized to mitochondria. In particular, the mitochondrial electron transport chain and nicotinamide-adenine dinucleotide phosphate oxidase 4 (Nox4) were responsible for the significant 15-HETE stimulated increase in ROS production. Moreover, ROS induced by 15-HETE stimulated endothelial cell (EC) migration and promoted pulmonary artery smooth muscle cell (PASMC) proliferation under hypoxia via the p38 MAPK pathway. These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling (PVR) via the p38 MAPK pathway. PMID- 26871727 TI - Belief in Family Planning Myths at the Individual and Community Levels and Modern Contraceptive Use in Urban Africa. AB - CONTEXT: Negative myths and misconceptions about family planning are a barrier to modern contraceptive use. Most research on the subject has focused on individual beliefs about contraception; however, given that myths spread easily within communities, it is also important to examine how the prevalence of negative myths in a community affects the aggregate level of method use. METHODS: Baseline data collected in 2010-2011 by the Measurement, Learning & Evaluation project on women aged 15-49 living in selected cities in Kenya, Nigeria and Senegal were used. Multivariate analyses examined associations between modern contraceptive use and belief in negative myths for individuals and communities. RESULTS: In each country, the family planning myths most prevalent at the individual and community levels were that "people who use contraceptives end up with health problems," "contraceptives are dangerous to women's health" and "contraceptives can harm your womb." On average, women in Nigeria and Kenya believed 2.7 and 4.6 out of eight selected myths, respectively, and women in Senegal believed 2.6 out of seven. Women's individual-level belief in myths was negatively associated with their modern contraceptive use in all three countries (odds ratios, 0.2-0.7). In Nigeria, the women's community-level myth variable was positively associated with modern contraceptive use (1.6), whereas the men's community-level myth variable was negatively associated with use (0.6); neither community-level variable was associated with modern contraceptive use in Kenya or Senegal. CONCLUSION: Education programs are needed to dispel common myths and misconceptions about modern contraceptives. In Nigeria, programs that encourage community-level discussions may be effective at reducing myths and increasing modern contraceptive use. PMID- 26871728 TI - Unmet Need for Family Planning in Sri Lanka: Low Enough or Still an Issue? AB - CONTEXT: Family planning efforts achieved considerable success in Sri Lanka during the late 20th century; however, overall levels and trends may mask relatively high levels of unmet need under certain conditions. METHODS: Data from the 2007 Demographic and Health Survey of Sri Lanka (DHS-SL) were used to estimate unmet need for limiting and spacing births among ever-married women aged 15-49, overall and by key characteristics. Twelve definitions of unmet need of varying stringency were used to assess the sensitivity of results to a variety of measurement issues. Comparable estimates from the 1987 DHS-SL were used to provide context on changes in unmet need over time. RESULTS: Total unmet need in 2007 ranged from 1.6% under the narrowest definition to 19.3% under the broadest. Levels of unmet need for spacing births in 2007 were lower than 3% for all measures and for most subsamples. In contrast, levels of unmet need for limiting were generally higher and more varied, both in relation to the definition of unmet need used and across subsamples. Unmet need for limiting was particularly high in certain groups if women's use of traditional contraceptive methods and practice of prolonged abstinence were considered not to meet their contraceptive need. CONCLUSIONS: Continued progress regarding contraceptive prevalence and method mix could contribute to further reducing unmet need for family planning in Sri Lanka and to meeting women's reproductive and health goals. Renewed policy emphasis on the family planning needs and concerns of selected groups would promote such goals. PMID- 26871729 TI - How Reliable Are Reports of Early Adolescent Reproductive and Sexual Health Events in Demographic and Health Surveys? AB - CONTEXT: Age at sexual debut, age at first marriage or first union and age at first birth are among the most widely used indicators of health and well-being for female adolescents. However, the accuracy of estimates for these indicators, particularly for younger adolescents, is poorly understood. METHODS: For each of nine countries in Africa and Latin America, Demographic and Health Survey (DHS) data from two surveys conducted five years apart were used to examine women's reports of age at sexual debut, marriage or first union, and first birth. The consistency of estimates between surveys and across birth cohorts is described, focusing particularly on the reporting of events occurring before age 15 and age 16. RESULTS: Marked differences in estimates for very early first births and marriage were found. Women aged 15-19 were much less likely to report marriages and first births before age 15 than were women from the same birth cohort when asked five years later at ages 20-24. Early sexual debut was reported more consistently in consecutive surveys than early marriages or births. CONCLUSIONS: Caution should be exercised when inferring changes in early adolescent sexual and reproductive health on the basis of estimates from the DHS. Greater effort should be made to develop data collection instruments that reduce misreporting of self reported data from women sampled in household surveys. PMID- 26871730 TI - Electrical pharyngeal stimulation increases substance P level in saliva. AB - BACKGROUND: Substance P (SP) is a neuropeptide known to enhance the swallow response. It likely acts as a neurotransmitter in the pharyngeal mucosa in response to local stimuli. It has been proposed that dysphagia after stroke may be related to reduced levels of SP, which therefore constitutes a therapeutic target. In the present pilot study, we evaluated whether electrical pharyngeal stimulation (EPS), a neuromodulation device to enhance cortical reorganization for the restoration of swallowing function after brain injury, is able to increase SP in saliva or serum. METHODS: In a randomized crossover study design, 20 healthy volunteers were treated with 10 min of real (0.2-ms pulses, 5 Hz, 280 V, stimulation intensity (mA) individually adjusted to tolerance level) or sham EPS on two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Blood and saliva samples were taken prior to, during, and up to 1 h after EPS and analyzed for their SP concentration by ELISA. KEY RESULTS: Following real EPS but not sham stimulation, SP levels in saliva increased immediately and significantly about 28% (p < 0.01) compared to baseline. Serum levels remained unchanged. CONCLUSIONS & INFERENCES: Electrical pharyngeal stimulation is able to induce pharyngeal SP release in healthy subjects. PMID- 26871731 TI - Systematic drug perturbations on cancer cells reveal diverse exit paths from proliferative state. AB - During a cell state transition, cells travel along trajectories in a gene expression state space. This dynamical systems framework complements the traditional concept of molecular pathways that drive cell phenotype switching. To expose the structure that hinders cancer cells from exiting robust proliferative state, we assessed the perturbation capacity of a drug library and identified 16 non-cytotoxic compounds that stimulate MCF7 breast cancer cells to exit from proliferative state to differentiated state. The transcriptome trajectories triggered by these drugs diverged, then converged. Chemical structures and drug targets of these compounds overlapped minimally. However, a network analysis of targeted pathways identified a core signaling pathway--indicating common stress response and down-regulation of STAT1 before differentiation. This multi trajectory analysis explores the cells' state transition with a multitude of perturbations in combination with traditional pathway analysis, leading to an encompassing picture of the dynamics of a therapeutically desired cell-state switching. PMID- 26871732 TI - Phosphate adsorption on lanthanum loaded biochar. AB - To attain a low-cost and high-efficient phosphate adsorbent, lanthanum (La) loaded biochar (La-BC) prepared by a chemical precipitation method was developed. La-BC and its pristine biochar (CK-BC) were comparatively characterized using zeta potential, BET surface area, scanning electron microscopy/energy dispersive spectrometer (SEM-EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The adsorption ability and the mechanisms during adsorption process for the La-BC samples were also investigated. La loaded on the surface of biochar can be termed as La-composites (such as LaOOH, LaONO3 and La(OH)3), leading to the decrease of negative charge and surface area of biochar. La-BC exhibited the high adsorption capacity to phosphate compared to CK-BC. Adsorption isotherm and adsorption kinetic studies showed that the Langmuir isotherm and second order model could well describe the adsorption process of La-BC, indicating that the adsorption was dominated by a homogeneous and chemical process. The calculated maximum adsorption capacity was as high as 46.37 mg g(-1) (computed in P). Thermodynamic analysis revealed that the adsorption was spontaneous and endothermic. SEM, XRD, XPS and FT-IR analysis suggested that the multi-adsorption mechanisms including precipitation, ligand exchange and complexation interactions can be evidenced during the phosphate adsorption process by La-composites in La-BC. PMID- 26871734 TI - Combining ECT with pharmacological treatment of depressed inpatients in a naturalistic study is not associated with serum BDNF level increase. AB - BACKGROUND: BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls. METHODS: Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group. RESULTS: There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00). CONCLUSION: Combination of ECT with pharmacological treatment did not result in increased serum BDNF levels and did not restore levels to that of controls. PMID- 26871733 TI - Substance use after bariatric surgery: A review. AB - BACKGROUND: Prevalence of obesity has increased dramatically. Obese individuals may undergo bariatric surgery to lose excessive body fat and mitigate obesity related comorbidities. However, bariatric patients are particularly vulnerable to substance use problems. We conducted a review to examine the prevalence change and factors associated with substance use and determine the association between substance use and health status after weight loss among bariatric patients. METHODS: We searched peer-reviewed articles published between January 1990 and January 2015 in several databases (PubMed, PsycINFO, Cochrane Library, Google Scholar) using different keywords combinations. Studies that focused on pre surgery substance use only or without reported effect measurements were excluded. RESULTS: Overall, 40 studies were included in the review. Preoperative history of substance use was a reliable correlate of postoperative substance use. The prevalence of postoperative alcohol use was higher among patients with preoperative history of alcohol use than those without. Postoperative prevalence of alcohol use ranged from 7.6% to 11.8%. No significant prevalence change in cigarette smoking from pre-to postoperative period was observed. Time effect was not observed on smoking or drug use prevalence, while an increase in alcohol consumption was inconsistent across studies. The proportion of new-onset substance users among bariatric patients after surgery ranged from 34.3% to 89.5%. CONCLUSION: Substance use is associated with poor health among bariatric patients. Preoperative assessment and postoperative follow-up should include interventions to reduce relapse among users and prevent substance use initiation. PMID- 26871735 TI - Protein cross-linking tools for the construction of nanomaterials. AB - Across bioengineering there is a need to couple proteins to other proteins, or to peptides. Although traditional chemical conjugations have dominated in the past, more and more highly specific coupling strategies are becoming available that are based on protein engineering. Here we review the use of protein modification approaches such as enzymatic and autocatalytic protein-protein coupling, as well as the use of hetero-dimerizing (or hetero-oligomerizing) modules, applied to the specific case of linking together de novo designed recombinant polypeptides into precisely structured nanomaterials. Such polypeptides are increasingly being investigated for biomedical and other applications. In this review, we describe the protein-engineering based cross-linking strategies that dramatically expand the repertoire of possible molecular structures and, hence, the range of materials that can be produced from them. PMID- 26871736 TI - Laser Writing Block Copolymer Self-Assembly on Graphene Light-Absorbing Layer. AB - Recent advance of high-power laser processing allows for rapid, continuous, area selective material fabrication, typically represented by laser crystallization of silicon or oxides for display applications. Two-dimensional materials such as graphene exhibit remarkable physical properties and are under intensive development for the manufacture of flexible devices. Here we demonstrate an area selective ultrafast nanofabrication method using low intensity infrared or visible laser irradiation to direct the self-assembly of block copolymer films into highly ordered manufacturing-relevant architectures at the scale below 12 nm. The fundamental principles underlying this light-induced nanofabrication mechanism include the self-assembly of block copolymers to proceed across the disorder-order transition under large thermal gradients, and the use of chemically modified graphene films as a flexible and conformal light-absorbing layers for transparent, nonplanar, and mechanically flexible surfaces. PMID- 26871737 TI - Controllable synthesis of few-layered and hierarchically porous boron nitride nanosheets. AB - Few-layered porous boron nitride nanosheets (BNNS) have been prepared using a dynamic magnesium diboride (MgB2) template and ammonium chloride (NH4Cl) etchant. Magnesium-based intermediates serve as layer separators in the synthesis and prevent extensive aggregation, resulting in few-layered BNNS. The resultant BNNS are hierarchically porous and show good CO2/N2 adsorption selectivity. PMID- 26871738 TI - Correction to "An Investigation of (Diacetoxyiodo)arenes as Precursors for Preparing No-Carrier-Added [(18)F]Fluoroarenes from Cyclotron-Produced [(18)F]Fluoride Ion". PMID- 26871739 TI - Nanoscale Imaging of Charge Carrier and Exciton Trapping at Structural Defects in Organic Semiconductors. AB - Charge carrier and exciton trapping in organic semiconductors crucially determine the performance of organic (opto-)electronic devices such as organic field-effect transistors, light-emitting diodes, or solar cells. However, the microscopic origin of the relevant traps generally remains unclear, as most spectroscopic techniques are unable to simultaneously probe the electronic and morphological structure of individual traps. Here, we employ low-temperature scanning tunneling microscopy (STM) and spectroscopy (STS) as well as tight-binding calculations derived from ab initio calculations to image the localized electronic states arising at structural defects in thin C60 films (<10 ML). The spatially and spectrally resolved STM-induced luminescence at these states reveals an enhanced radiative decay of excitons, which is interpreted in terms of the local symmetry lowering and the trapping of excitons by an X-trap. The combined mapping of the STM-induced luminescence, electronic structure, and morphology thus provides new insights into the origin and characteristics of individual exciton traps in organic semiconductors and offers new avenues to study charge carrier and exciton dynamics on molecular scales. PMID- 26871740 TI - Data graphs and mechanistic explanation. AB - It is a widespread assumption in philosophy of science that representations of data are not explanatory-that they are mere stepping stones towards an explanation, such as a representation of a mechanism. I draw on instances of representational and explanatory practice from mammalian chronobiology to suggest that this assumption is unsustainable. In many instances, biologists employ representations of data in explanatory ways that are not reducible to constraints on or evidence for representations of mechanisms. Data graphs are used to represent relationships between quantities across conditions, and often these representations are necessary for explaining particular aspects of the phenomena under study. The benefit of the analysis is two-fold. First, it provides a more accurate account of explanatory practice in broadly mechanistic investigation in biology. Second, it suggests that there is not an explanatorily "fundamental" type of representation in biology. Rather, the practice of explanation consists in the construction of different types of representations and their employment for distinct explanatory purposes. PMID- 26871741 TI - Direct Evidence of a Tryptophan Analogue Radical Formed in a Concerted Electron Proton Transfer Reaction in Water. AB - Proton-coupled electron transfer (PCET) is a fundamental reaction step of many chemical and biological processes. Well-defined biomimetic systems are promising tools for investigating the PCET mechanisms relevant to natural proteins. Of particular interest is the possibility to distinguish between stepwise and concerted transfer of the electron and proton, and how PCET is controlled by a proton acceptor such as water. Thus, many tyrosine and phenolic derivatives have been shown to undergo either stepwise or concerted PCET, where the latter process is defined by simultaneous tunneling of the electron and proton from the same transition state. For tryptophan instead, it is theoretically predicted that a concerted pathway can never compete with the stepwise electron-first mechanism (ETPT) when neat water is the primary proton acceptor. The argument is based on the radical pK(a) (~4.5) that is much higher than that for water (pK(a)(H3O(+)) = 0), which thermodynamically disfavors a concerted proton transfer to H2O. This is in contrast to the very acidic radical cation of tyrosine (pK(a) ~ -2). However, in this study we show, by direct time-resolved absorption spectroscopy on two [Ru(bpy)3](2+)-tryptophan (bpy = 2,2'-bipyridine) analogue complexes, that also tryptophan oxidation with water as a proton acceptor can occur via a concerted pathway, provided that the oxidant has weak enough driving force. This rivals the theoretical predictions and suggests that our current understanding of PCET reactions in water is incomplete. PMID- 26871742 TI - Performance of signal-to-noise ratio estimation for scanning electron microscope using autocorrelation Levinson-Durbin recursion model. AB - A new technique to quantify signal-to-noise ratio (SNR) value of the scanning electron microscope (SEM) images is proposed. This technique is known as autocorrelation Levinson-Durbin recursion (ACLDR) model. To test the performance of this technique, the SEM image is corrupted with noise. The autocorrelation function of the original image and the noisy image are formed. The signal spectrum based on the autocorrelation function of image is formed. ACLDR is then used as an SNR estimator to quantify the signal spectrum of noisy image. The SNR values of the original image and the quantified image are calculated. The ACLDR is then compared with the three existing techniques, which are nearest neighbourhood, first-order linear interpolation and nearest neighbourhood combined with first-order linear interpolation. It is shown that ACLDR model is able to achieve higher accuracy in SNR estimation. PMID- 26871743 TI - First report of Lecanodiaspis dendrobii Douglas, 1892 (Hemiptera: Lecanodiaspididae) and the associated parasitoid Cephaleta sp. (Hymenoptera: Pteromalidae) in Brazil. AB - Lecanodiaspis dendrobii Douglas, 1892 (Hemiptera: Coccoidea: Lecanodiaspididae) and the associated parasitoid Cephaleta sp. (Hymenoptera: Pteromalidae) are reported for the first time in Brazil. Specimens of this scale insect were collected on branches and stems of Acacia mangium Willd., Leucaena leucocephala (Lam.) de Wit (Fabaceae), Morus nigra L. (Moraceae), Citrus reticulata Blanco (Rutaceae), Tectona grandis L. f. (Verbenaceae), Anacardium occidentale (Anacardiaceae), Annona squamosa L. and Xylopia aromatica (Lam.) Mart. (Annonaceae), in three municipalities of the Roraima state. All plants here mentioned are recorded for the first time as a host for L. dendrobii. Morphological characters of L. dendrobii and symptoms presented by the host plants infested by this pest are included in this work. PMID- 26871744 TI - Antimicrobial and antioxidant activity of essential oil and different plant extracts of Psidium cattleianum Sabine. AB - The goals of the study were to determinethe antimicrobial and antioxidant activities of essential oil and plant extracts aqueous and ethanolic of Psidium cattleianum Sabine; the chemical composition of the essential oil of P. cattleianum; and the phytochemical screening of aqueous and ethanolic extracts of the same plant. Regarding the antimicrobial activity, the ethanolic extract exhibited moderate antimicrobial activity with respect to bacteria K. pneumoniae and S. epidermidis, whereas, regarding other microorganisms, it showed activity considered weak. The aqueous extract and the essential oil showed activity considered weak, although they inhibited the growth of microorganisms. About the antioxidant potential, the ethanolic and aqueous extracts exhibited a scavenging index exceeding 90%, while the essential oil didn't show significant antioxidant activity. Regarding the phytochemical composition, the largest class of volatile compounds identified in the essential oil of P. cattleianum included the following terpenic hydrocarbons: alpha-copaene (22%); eucalyptol (15%), delta cadinene (9.63%) and alpha-selinene (6.5%). The phytochemical screening of extracts showed the presence of tannins, flavonoids, and triterpenoids for aqueous and ethanolic extracts. The extracts and essential oils inhibit the growth of microrganisms and plant extracts showed significant antioxidant activity. Also, the phytochemical characterization of the essential oil showed the presence of compounds interest commercial, as well as extracts showed the presence of important classes and compounds with biological activities. PMID- 26871745 TI - Home range and density of three sympatric felids in the Southern Atlantic Forest, Brazil. AB - Home range and minimal population densities of Southern tiger cat (Leopardus guttulus), margay (Lepardus wiedii) and jaguarundi (Puma yagouaroundi) were estimated between 2005 and 2006 in Taquari Valley, near the southern edge of the Atlantic Rainforest in Brazil. Home range data were collected by conventional radio telemetry (VHF) locations in a highly fragmented landscape. The average home range size, calculated using 95% kernel density estimates, was 16.01 km2 for Southern tiger cat, 21.85 km2 for margay and 51.45 km2 for jaguarundi. Telemetry data were used to obtain minimal density estimates of 0.08 Southern tiger cats / km2, and 0.04 jaguarundi / km2. The density estimates arise from areas where ocelot (Leopardus pardalis) and other larger-bodied carnivores were locally extinct, and they suggest a specific type of mesopredator release known as the ocelot effect, which is likely enabling the increase in smaller felid populations in this area. PMID- 26871746 TI - Seasonal variability of the essential oil of Hesperozygis ringens (Benth.) Epling. AB - This study was developed to evaluate the effect of seasonality on the yield and chemical composition of the essential oil (EO) of Hesperozygis ringens (Benth.) Epling, a native species from the Brazilian Pampa. Leaves were collected from four specimens of a single population in each of the four seasons for a year and were extracted in triplicate by hydro-distillation for 2 hours. The yield of EO (% w/w) was calculated on fresh weight basis (FWB), and the 16 oil samples were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) were used as statistical tools to evaluate differences in chemical composition. The highest yields were obtained in autumn, spring and summer (2.32-4.38%), while the lowest yields were detected in winter, ranging from 1.15 to 1.91%. Oxygenated monoterpenoids were the predominant class of chemical constituents in the EO obtained in all seasons, showing the highest contents in autumn and summer, and pulegone was identified as a major compound, whose contents varied between 54.13 and 81.17%. The EO samples were divided into three chemical groups by HCA and PCA and were assigned to the same group, except for the three samples gathered in winter. The results showed a seasonal influence on the yield and chemical composition of the EO. PMID- 26871747 TI - Effects of water-soluble fraction of petroleum on growth and prey consumption of juvenile Hoplias aff. malabaricus (Osteichthyes: Erythrinidae). AB - The influence of the water-soluble fraction of petroleum (WSF) on prey consumption and growth of juvenile trahira Hoplias aff. malabaricus was investigated. Juveniles were submitted to either WSF or Control treatment over 28 days, and jewel tetra Hyphessobrycon eques adults were offered daily as prey for each predator. Total prey consumption ranged from 16 to 86 individuals. Despite the initially lower prey consumption under WSF exposure, there were no significant differences in overall feeding rates between the two treatments. Water-soluble fraction of petroleum had a negative effect on the growth in length of H. aff. malabaricus juveniles. Although unaffected, prey consumption suggested a relative resistance in H. aff. malabaricus to WSF exposition and the lower growth of individuals exposed to WSF than the Control possibly reflects metabolic costs. The implications of the main findings for the individual and the food chain are discussed, including behavioral aspects and the role played by this predator in shallow aquatic systems. PMID- 26871748 TI - Floral morphology and anatomy of Dalechampia alata Klotzsch ex Baill. (Euphorbiaceae), with emphasis on secretory structures. AB - The morphology and anatomy of the flower of Dalechampia alata, as well as the chemical nature of the exudates secreted in the inflorescence were studied using light microscope. This is the first report showing the presence of colleters in the genus Dalechampia. In the staminate flower occur a group of small secretory glands. The histochemical results indicate that the substance secreted from the glands is lipidic and resinuous in nature, while in the colleters it consists of polysaccharides and lipid-rich substances. The ovule of D. alata are anatropous, subglobose and bitegmic. It presents obturator, micropyle occluded by nucellar beak and meristematic activity in the ovary wall. The secretion produced in the stigmatic and transmitting tissue consists of polysaccharides. PMID- 26871749 TI - The role of Pteridium arachnoideum(Kaulf) on the seed bank of the endangered Brazilian Cerrado. AB - The native bracken (Pteridium arachnoideum) often occurs in mono-specific stands in the Brazilian Cerrado, and this dominance can impact on both the above-ground vegetation and soil seed bank. This study investigated how invasion by this species over a 20-year period changed the seed bank and the relationship between the seed bank and litter mass. We extracted soil samples from three replicated invaded and uninvaded sites, and followed seedling emergence for six months. We collected the above-ground biomass and litter of P. arachnoideum in ten 1m2 plots from three invaded sites. There was no difference between invaded and uninvaded areas in seed bank richness, diversity or overall abundance. The most abundant family was the Melastomataceae, followed by the Poaceae. The Melastomataceae was more abundant in uninvaded sites, but the most common species of this family (Tibouchinastenocarpa) was not affected. The grasses were more common in invaded sites in the rainy season and were affected by heterogeneity in the litter layer. The seed bank could play a role in the recovery of these invaded areas, but the presence of weeds and invasive grasses could constrain their use as a management strategy. PMID- 26871750 TI - Limnoperna fortunei Dunker, 1857 larvae in different environments of a Neotropical floodplain: relationships of abiotic variables and phytoplankton with different stages of development. AB - Limnoperna fortunei Dunker, 1857 is an Asian invasive freshwater bivalve. Although there need to contain their spread, studies about the biology of the larvae are scarce. We correlated the larval stages of L. fortunei with biotic factors such as phytoplankton and main abiotic variables in lotic environments of the Upper Parana River floodplain. The four samples were taken quarterly during the year 2012. The Principal component analysis (PCA) showed only spatial differences, as did a Canonical Correspondence Analysis (CCA). High densities of larvae were recorded in all samples the Parana River and Baia River only in December, especially those in their initial stage. In the biovolume of Class of algae, Bacillarophyceae showed the highest value, but Chlorophycea who was strongly correlated with the density of D-stage larvae. The large variety of phytoplankton, especially microplankton Chlorophyceae, high values of PO4, NH4 and temperature were positively correlated with high densities of D-stage larvae. We conclude that high temperature, and food availability, indicated by phytoplankton community, favored the reproduction of L. fortunei and enhance the ability of specie dispersion due to the increase in the emission of propagules. Therefore, studies that address the biology of golden mussel larvae should be performed in order to prevent its spread. PMID- 26871751 TI - Mites occurrence on Pachira aquatica Aubl. including aspects of external mouthpart morphology of Brachytydeus formosa (Acari: Tydeidae). AB - Pachira aquatica Aubl. is commonly used as an ornamental plant in urban areas of Brazil. The objective of the study was to investigate the occurrence of mites on P. aquatica, with emphasis on Brachytydeus formosa (Cooreman), and to describe aspects the external features of its mouthpart. The study was conducted in 2012 in Jaboticabal, State of Sao Paulo, Brazil. Ten trees of P. aquatica were selected for the experiment. Approximately 130 leaflets were collected from each tree, which were located in different quadrants (north, south, east, and west) and strata (upper, middle, and lower). The leaflets were placed in paper bags and transported to the laboratory. The mites were prepared on optical microscope slides. A total of eleven species of mites were found, belonging to eight different families. The species and genera of the organisms included B. formosa, Eutetranychus banksi (McGregor), Agistemus sp., Tyrophagus putrescentiae (Schrank, 1781), Brevipalpus phoenicis (Geijskes), Brevipalpus sp., Cheletogenes sp., Iphiseiodes zuluagai Denmark & Muma, Euseius sp., Neoseiulus sp., and only one specimen from the Bdellidae family. The predominant species was B. formosa, with 8,142 mites equally distributed among the four quadrants and mostly in the middle and upper strata of the plant. B. formosa mites from leaflets of P. aquatica were separated for the study of the external mouthpart morphology by scanning electron microscopy (SEM). PMID- 26871752 TI - Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano materials. AB - Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology. PMID- 26871753 TI - Allostery in molecular self-assemblies: metal ions triggered self-assembly and emissions of terthiophene. AB - Binding of metal ions to the head of a coordinating amphiphile TTC4L substantially changes the emission color of the terthiophene group attached to the chain end via a conformation triggered self-assembly. This is in analogy with the allostery of proteins in which binding a ligand to one site may affect its performance at another site through conformational change. PMID- 26871754 TI - Isomorphous Substitution of Rare-Earth Elements in Lacunary Apatite Pb8Na2(PO4)6. AB - The substitution of rare-earth elements (REEs) for Pb in the lacunary apatite Pb8Na2(PO4)6 with void structural channels was studied by means of powder X-ray diffraction (including the Rietveld refinement), scanning electron microscopy, energy-dispersive X-ray microanalysis, and IR spectroscopy and also measurements of the electrical conductivity. The substitution limits (xmax in Pb8 xLnxNa2(PO4)6Ox/2) at 800 degrees C were found to decrease with the atomic number of the REE from 1.40 for La to 0.12 for Yb with a rapid drop from light to heavy lanthanides (between Gd and Tb). The REE atoms substitute for Pb predominantly at Pb2 sites of the apatite structure according to the scheme 2Pb(2+) + ? -> 2Ln(3+) + O(2-), where ? is a vacancy in the structural channel. The substitution in lacunary apatite produces quite different changes in the structural parameters compared with broadly studied alkaline-earth hydroxyapatites. In spite of the much lower ionic radii of REE than that of Pb(2+), the mean distances ?Pb1-O? somewhat increase, whereas the distances ?Pb2 Pb2? and ?Pb2-O4? do not change considerably with the degree of substitution. This implies control of the substitution by not only spatial and charge accommodation of REE ions but also the availability of a stereochemically active 6s(2) electron pair on Pb(2+). The high-temperature electrical conductivity shows dependence on the degree of substitution with a minimum at x = 0.2 indicative of a possible change of the type of conductivity. PMID- 26871757 TI - Cyanophenyl vs. pyridine substituent: impact on the adlayer structure and formation on HOPG and Au(111). AB - A new cyano substituted bis(terpyridine) derivative CN-BTP was synthesized and its adsorption on highly oriented pyrolytic graphite (HOPG) and Au(111) was investigated. CN-BTP is closely related to the previously investigated 2,4'-BTP, where the cyanophenyl groups are replaced by pyridine moieties. The scanning tunneling microscopy (STM) investigation of CN-BTP at the liquid|HOPG interface shows a highly ordered herringbone structure that is stabilized by double weak intermolecular C-HN hydrogen bonds, partially through the -CN substituents, which is different from the most stable square structure of 2,4'-BTP. The adsorption processes were investigated using cyclic voltammetry (CV) on Au(111) in a neutral phosphate buffer. A fast and full adlayer formation could be observed with CN BTP, whereas an extremely slow process with 2,4'-BTP under the same conditions was found. Our data show that the CN substituents on BTP not only change the structure of the monolayer at the liquid|HOPG interface, but also accelerate the phase transition process in the electrolyte dramatically. This could be explained by the adlayer-substrate interactions, which is supported by DFT calculations. Our findings might be extended more generally to further pyridine comprising self assembling molecules to fine-tune the adlayer structure and phase transition/adsorption kinetics by replacing pyridine by cyanophenyl moieties. PMID- 26871755 TI - Contributions of Coulombic and Hofmeister Effects to the Osmotic Activation of Escherichia coli Transporter ProP. AB - Osmosensing transporters mediate osmolyte accumulation to forestall cellular dehydration as the extracellular osmolality increases. ProP is a bacterial osmolyte-H(+) symporter, a major facilitator superfamily member, and a paradigm for osmosensing. ProP activity is a sigmoid function of the osmolality. It is determined by the osmolality, not the magnitude or direction of the osmotic shift, in cells and salt-loaded proteoliposomes. The activation threshold varies directly with the proportion of anionic phospholipid in cells and proteoliposomes. The osmosensory mechanism was probed by varying the salt composition and concentration outside and inside proteoliposomes. Data analysis was based on the hypothesis that the fraction of maximal transporter activity at a particular luminal salt concentration reflects the proportion of ProP molecules in an active conformation. ProP attained the same activity at the same osmolality when diverse, membrane-impermeant salts were added to the external medium. Contributions of Coulombic and/or Hofmeister salt effects to ProP activation were examined by varying the luminal salt cation (K(+) and Na(+)) and anion (chloride, phosphate, and sulfate) composition and then systematically increasing the luminal salt concentration by increasing the external osmolality. ProP activity increased with the sixth power of the univalent cation concentration, independent of the type of anion. This indicates that salt activation of ProP is a Coulombic, cation effect resulting from salt cation accumulation and not site-specific cation binding. Possible origins of this Coulombic effect include folding or assembly of anionic cytoplasmic ProP domains, an increase in local membrane surface charge density, and/or the juxtaposition of anionic protein and membrane surfaces during activation. PMID- 26871756 TI - The ergogenic supplement beta-hydroxy-beta-methylbutyrate (HMB) attenuates insulin resistance through suppressing GLUT-2 in rat liver. AB - This study investigates the effect of the ergogenic supplement beta-hydroxy-beta methylbutyrate (HMB) on insulin resistance induced by high-fructose diet (HFD) in rats. Male Sprague Dawley rats were fed 60% HFD for 12 weeks and HMB (320 mg.kg( 1).day(-1), orally) for 4 weeks. HFD significantly increased fasting insulin, fasting glucose, glycosylated hemoglobin (HBA1C), liver glycogen content, and homeostasis model assessment of insulin resistance (HOMA-IR) index, while it decreased glucose and insulin tolerance. Furthermore, HFD significantly increased serum triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL-C) levels, while it significantly decreased high density lipoprotein cholesterol (HDL-C). Moreover, HFD significantly increased mRNA expression of glucose transporter type-2 (GLUT-2), the mammalian target of rapamycin (mTOR), and sterol regulatory element-binding protein-1c (SREBP-1c) but decreased peroxisome proliferator-activated receptor alpha (PPAR-alpha) in liver. Aortic relaxation to acetylcholine (ACh) was impaired and histopathology showed severe hepatic steatosis. HMB significantly increased insulin tolerance and decreased fasting insulin, HOMA-IR, HBA1C, hepatic glycogen content, serum TG, LDL-C, and VLDL-C. Additionally, HMB enhanced ACh-induced relaxation, ameliorated hepatic steatosis, and decreased mRNA expression of GLUT-2. In conclusion, HMB may attenuate insulin resistance and hepatic steatosis through inhibiting GLUT-2 in liver. PMID- 26871758 TI - Racial and Gender Differences in Dating Violence Victimization and Disordered Eating Among U.S. High Schools. AB - BACKGROUND: In 2013, 1 in every 10 students who dated or went out with someone in the previous 12 months reported some form of dating violence (DV). Only a few studies have evaluated the relationship between DV and disordered eating (DE). This study aims to evaluate gender differences in the association between DV victimization and DE behaviors using a nationally representative sample of high school students in the United States. MATERIALS AND METHODS: Data came from the 2013 National Youth Risk Behavior Survey. Students who reported dating or going out with anyone in the previous 12 months and responded to DV and DE questions were included (N = 9,677). DV was categorized as physical DV, sexual DV, physical and sexual DV, and none. The outcome, or DE, was determined by questions about unhealthy weight control behaviors. Multiple logistic regression models provided odds ratios (ORs) and 95% confidence intervals. Race/ethnicity was an effect modifier; thus, stratified analyses assessed for gender and racial/ethnic differences. RESULTS: The prevalence of past-year physical DV, sexual DV, both physical and sexual DV, and any DV was 5.4%, 5.4%, 4.7%, and 15.5%, respectively. OR estimates were more robust in males than in females. Victims of physical and sexual DV were significantly more likely to report DE, namely among Hispanic and non-Hispanic White males and all female race/ethnic groups, with the exception of non-Hispanic Black females. CONCLUSIONS: Findings strengthen support for routine DV screening. Adolescent violence prevention programs should consider risky behaviors, such as DE. Interventions should account for gender and racial/ethnic differences. PMID- 26871761 TI - Peripheral iridotomy for pigmentary glaucoma. AB - BACKGROUND: Glaucoma is a chronic optic neuropathy characterized by retinal ganglion cell death resulting in damage to the optic nerve head and the retinal nerve fiber layer. Pigment dispersion syndrome is characterized by a structural disturbance in the iris pigment epithelium (the densely pigmented posterior surface of the iris) that leads to dispersion of the pigment and its deposition on various structures within the eye. Pigmentary glaucoma is a specific form of open-angle glaucoma found in patients with pigment dispersion syndrome.Topcial medical therapy is usually the first-line treatment; however, peripheral laser iridotomy has been proposed as an alternate treatment. Peripheral laser iridotomy involves creating an opening in the iris tissue to allow drainage of fluid from the posterior chamber to the anterior chamber and vice versa. Equalizing the pressure within the eye may help to alleviate the friction that leads to pigment dispersion and prevent visual field deterioration. However, the effectiveness of peripheral laser iridotomy in reducing the development or progression of pigmentary glaucoma is unknown. OBJECTIVES: The objective of this review was to assess the effects of peripheral laser iridotomy compared with other interventions, including medication, trabeculoplasty, and trabeculectomy, or no treatment, for pigment dispersion syndrome and pigmentary glaucoma. SEARCH METHODS: We searched a number of electronic databases including CENTRAL, MEDLINE and EMBASE and clinical trials websites such as (mRCT) and ClinicalTrials.gov. We last searched the electronic databases on 2 November 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that had compared peripheral laser iridotomy versus no treatment or other treatments for pigment dispersion syndrome and pigmentary glaucoma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures for systematic reviews. Two review authors independently screened articles for eligibility, extracted data, and assessed included trials for risk of bias. We did not perform a meta-analysis because of variability in reporting and follow-up intervals for primary and secondary outcomes of interest. MAIN RESULTS: We included five RCTs (260 eyes of 195 participants) comparing yttrium-aluminum-garnet (YAG) laser iridotomy versus no laser iridotomy. Three trials included participants with pigmentary glaucoma at baseline, and two trials enrolled participants with pigment dispersion syndrome. Only two trials reported the country of enrollment: one - Italy, the other - United Kingdom. Overall, we assessed trials as having high or unclear risk of bias owing to incomplete or missing data and selective outcome reporting.Data on visual fields were available for one of three trials that included participants with pigmentary glaucoma at baseline. At an average follow-up of 28 months, the risk of progression of visual field damage was uncertain when comparing laser iridotomy with no iridotomy (risk ratio (RR) 1.00, 95% confidence interval (95% CI) 0.16 to 6.25; 32 eyes; very low-quality evidence). The two trials that enrolled participants with pigment dispersion syndrome at baseline reported the proportion of participants with onset of glaucomatous visual field changes during the study period. At three-year follow-up, one trial reported that the risk ratio for conversion to glaucoma was 2.72 (95% CI 0.76 to 9.68; 42 eyes; very low quality evidence). At 10-year follow-up, the other trial reported that no eye showed visual field progression.One trial reported the mean change in intraocular pressure (IOP) in eyes with pigmentary glaucoma: At an average of nine months of follow-up, the mean difference in IOP between groups was 2.69 mmHg less in the laser iridotomy group than in the control group (95% CI -6.05 to 0.67; 14 eyes; very low-quality evidence). This trial also reported the mean change in anterior chamber depth at an average of nine months of follow-up and reported no meaningful differences between groups (mean difference 0.04 mm, 95% CI -0.07 to 0.15; 14 eyes; very low-quality evidence). No other trial reported mean change in anterior chamber depth. Two trials reported greater flattening of iris configuration in the laser iridotomy group than in the control group among eyes with pigmentary glaucoma; however, investigators provided insufficient data for analysis. No trial reported data related to mean visual acuity, aqueous melanin granules, costs, or quality of life outcomes.Two trials assessed the need for additional treatment for control of IOP. One trial that enrolled participants with pigmentary glaucoma reported that more eyes in the laser iridotomy group required additional treatment between six and 23 months of follow-up than eyes in the control group (RR 1.73, 95% CI 1.08 to 2.75; 46 eyes); however, the other trial enrolled participants with pigment dispersion syndrome and indicated that the difference between groups at three-year follow-up was uncertain (RR 0.91, 95% CI 0.38 to 2.17; 105 eyes). We graded the certainty of evidence for this outcome as very low.Two trials reported that no serious adverse events were observed in either group among eyes with pigment dispersion syndrome. Mild adverse events included postoperative inflammation; two participants required cataract surgery (at 18 and 34 months after baseline), and two participants required a repeat iridotomy. AUTHORS' CONCLUSIONS: We found insufficient evidence of high quality on the effectiveness of peripheral iridotomy for pigmentary glaucoma or pigment dispersion syndrome. Although adverse events associated with peripheral iridotomy may be minimal, the long-term effects on visual function and other patient important outcomes have not been established. Future research on this topic should focus on outcomes that are important to patients and the optimal timing of treatment in the disease process (eg, pigment dispersion syndrome with normal IOP, pigment dispersion syndrome with established ocular hypertension, pigmentary glaucoma). PMID- 26871762 TI - The Impact of Personalized Preventive Care on Health Care Quality, Utilization, and Expenditures. AB - The objective of this study was to evaluate the impact on health care utilization and expenditure trends over time of a personalized preventive medicine program delivering individualized care focused on lifestyle behavior modification, disease prevention, and compliance with quality-related metrics. MD-Value in Prevention (MDVIP) is a network of affiliated primary care physicians who utilize a model of health care delivery based on an augmented physician-patient relationship and focused on personalized preventive health care. Multivariate modeling was used to control for demographics, socioeconomics, supply of health care services, and health status among 10,186 MDVIP members and randomly selected, matched nonmembers. Health care utilization and expenditure trends were tracked from the pre period prior to member enrollment for a period of up to 3 years post enrollment. MDVIP members experienced reduced utilization of emergency room and urgent care services compared to nonmembers. Program savings ranges indicated that, over time, increasing percentages of members achieved cost savings compared to nonmembers. Older age groups were more likely to realize savings in the early years with preventive activities indicating condition management, and younger age groups were most likely to achieve savings by the third year after enrollment. These results indicate that a primary care model based on an enhanced physician-patient relationship and focused on quality and personalized preventive care within a time frame of 3 years can achieve positive health care expenditure outcomes and improved health management. PMID- 26871763 TI - Neurological PRESentations in Sickle Cell Patients Are Not Always Stroke: A Review of Posterior Reversible Encephalopathy Syndrome in Sickle Cell Disease. AB - Acute neurological changes in sickle cell disease (SCD) patients often raise the suspicion for stroke. Posterior reversible encephalopathy syndrome (PRES) can mimic stroke in its clinical presentation. We aimed to (i) review the PRES literature in SCD patients including clinical presentation, risk factors, pathophysiology, and management and (ii) elucidate the distinction between PRES and stroke in SCD. The exact pathophysiology of PRES in SCD remains elusive but is likely multifactorial and related to sickling, ischemia, and chronic anemia predisposing to vasogenic edema. PRES and stroke in SCD are distinguishable conditions. Our review may help elucidate a clinical approach to this distinction. PMID- 26871764 TI - Single-Step Transepithelial PRK vs Alcohol-Assisted PRK in Myopia and Compound Myopic Astigmatism Correction. AB - Transepithelial photorefractive keratectomy (tPRK), where both the epithelium and stroma are removed in a single-step, is a relatively new procedure of laser refractive error correction. This study compares the 3-month results of myopia and compound myopic astigmatism correction by tPRK or conventional alcohol assisted PRK (aaPRK).This prospective, nonrandomized, case-control study recruited 148 consecutive patients; 93 underwent tPRK (173 eyes) and 55 aaPRK (103 eyes). Refractive results, predictability, safety, and efficacy were evaluated during the 3-month follow-up. The main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and mean refractive spherical equivalent (MRSE).Mean preoperative MRSE was -4.30 +/- 1.72 D and -4.33 +/- 1.96 D, respectively (P = 0.87). The 3-month follow-up rate was 82.1% in the tPRK group (n = 145) and 86.4% in aaPRK group (n = 90), P = 0.81. Postoperative UDVA was 20/20 or better in 97% and 94% of eyes, respectively (P = 0.45). In the tPRK and aaPRK groups, respectively, 13% and 21% of eyes lost 1 line of CDVA, and 30% and 31% gained 1 or 2 lines (P = 0.48). Mean postoperative MRSE was -0.14 +/- 0.26 D in the tPRK group and -0.12 +/- 0.20 D in the aaPRK group (P = 0.9). The correlation between attempted versus achieved MRSE was equally high in both groups.Single-step transepithelial PRK and conventional PRK provide very similar results 3 months postoperatively. These procedures are predictable, effective, and safe for correction of myopia and compound myopic astigmatism. PMID- 26871765 TI - Childhood Body Weight in Relation to Cause-Specific Mortality: 67 Year Follow-up of Participants in the 1947 Scottish Mental Survey. AB - The association between childhood body weight and adult health has been little examined, and findings are inconsistent.In a representative sample of the Scottish nation (the Scottish Mental Survey of 1947), we examined the association between body mass index measured at 11 years of age and future cause-specific mortality by age 77 years. In this cohort study, a maximum of 67 years of follow up of 3839 study members gave rise to 1568 deaths (758 from cardiovascular disease, 610 from any malignancy). After adjustment for covariates, there was some evidence of a relation between elevated childhood body mass index and rates of mortality ascribed to all-causes (hazard ratio per 1 SD increase in body mass index; 95% confidence interval: 1.09; 1.03, 1.14), cardiovascular disease (1.09; 1.01, 1.17), all cancers combined (1.12; 1.03, 1.21), smoking-related cancers (1.13; 1.03, 1.25), and breast cancer in women (1.27; 1.04, 1.56).In conclusion, we provide further observational evidence for the need for weight control measures in youth. PMID- 26871766 TI - Neurological Sequelae in Adults After E coli O104: H4 Infection-Induced Hemolytic Uremic Syndrome. AB - In an outbreak of shiga toxin-producing Escherichia coli infections and associated hemolytic-uremic syndrome (STEC O104:H4) in Germany in the year 2011 neurological complications in adult patients occurred unexpectedly frequent, ranging between 48% and 100% in different patient groups. Few is known about the long-term effects of such complications and so we performed follow-up exams on 44 of the patients treated for STEC-HUS at Hannover Medical Scool in this observational study. Standardized follow-up exams including neurological and neuropsychological assessments, laboratory testing, magnetic resonance imaging (MRI), and EEG were carried out. Subgroups were examined 2 (n = 34), 7 (n = 22), and 19 (n = 23) months after disease onset. Additionally, at the 19-month follow up, quality of life, sleep quality, and possible fatigue were assessed.Nineteen months after disease onset 31 patients were reassessed, 22 of whom still suffered from symptoms such as fatigue, headache, and attention deficits. In the neuropsychological assessments only 39% of the patients performed normal, whereas 61% scored borderline pathological or lower. Upon reviewal, the follow-up data most prominently showed a secondary decline of cognitive function in about one quarter of the patients. Outcome was not related to treatment or laboratory data in the acute phase of the disease nor length of hospitalization. Prognosis of STEC-HUS associated brain dysfunction in adults with regard to severity of symptoms is mostly good; some patients however still have not made a full recovery. Patients' caretakers have to be aware of possible secondary decline of brain function as was observed in this study. PMID- 26871767 TI - The Impact of Oral Hygiene Maintenance on the Association Between Periodontitis and Osteoporosis: A Nationwide Population-Based Cross Sectional Study. AB - Both periodontitis and osteoporosis have similar sign of bone resorption in nature. However, the relationship of the severity between these 2 bone-loss diseases is still uncertain.The aim of this study was to investigate the association between the severity of osteoporosis and periodontitis regarding the impact of oral hygiene maintenance. In total, 35,127 osteoporosis patients and 50,498 comparisons were derived from the Longitudinal Health Insurance Database of Taiwan between 2000 and 2010. The population was subdivided into groups according to the different level oral hygiene maintenance and the severity of periodontitis and osteoporosis. The association between osteoporosis and periodontitis was estimated by multinomial logistic regression and rank correlation by Kendall rank correlation test, presented by odds ratio (OR), and 5% confidence intervals (CIs).After controlling the age, sex, and comorbidities, variables in the good oral hygiene maintenance population, we found that periodontitis raised 1.29-fold risk of osteoporosis (95% CI = 1.12-1.49); the risk of osteoporosis was increased with the elevated severity of periodontitis from 1.27 (95% CI = 1.08-1.48) to 1.38 (95% CI = 1.01-1.89). There is a positive correlation between the severity of periodontitis and osteoporosis occurrence in this population (OR = 1.27-1.46; Kendall rank correlation test P = 0.0003). In the poor oral hygiene maintenance population, periodontitis patients had 6.02 fold risk of osteoporosis than those who without periodontitis (95% CI = 4.65 7.81); the risk of osteoporosis was increased with periodontitis severity from 5.96 (95% CI = 4.48-7.92) to 6.37 (95% CI = 3.36-12.1).This result indicated the periodontitis and osteoporosis are conjunctive. The sudden periodontal breakdown of those who with good oral hygiene maintenance might be an indicator for the risk of osteoporosis; if those who were diagnosed as osteoporosis must pay more attention to their periodontal health. Good oral hygiene maintenance might be a crucial factor for preventing the deterioration of osteoporosis progressing; the oral hygiene maintenance plays a significant influence on the association between periodontitis and osteoporosis. PMID- 26871768 TI - SUVmax and Tumor Size Predict Surgical Outcome of Synchronous Multiple Primary Lung Cancers. AB - To assess surgical outcomes in synchronous multiple primary lung cancer (SMPLC) and correlations with clinicopathological features and prognostic/predictive factors.We retrospectively reviewed patients diagnosed with early-stage nonsmall cell lung cancer (NSCLC) between January 2006 and June 2012. In total, 564 patients with resectable NSCLC underwent a preoperative positron emission tomography-computed tomography scan followed by anatomic resection. We reviewed the clinical features of 35 SMPLC patients. Surgical outcomes, prognosis, and tumor imaging features were evaluated (median follow-up = 44 months).In total, 35 eligible SMPLC patients (6.21%) were identified (11 men [31%], 24 women [69%], mean age = 65 years]). The tumors were bilateral in 17 patients (49%) and in different lobes of the ipsilateral lung in 18 patients (51%). Most patients (26/35, 74%) had 2 primary tumors, and 26% (9/35) had more than 2 tumors (6 with 3 tumors; 3 with 4 tumors). The median size of the most advanced tumor was 3.0 cm (range 0.9-54). The median standard uptake value (SUV) of the largest tumor was 3.1 (range 1.0-13.3). The patients were treated as follows: 30 lobectomies, 2 sublobar resections, 2 sequential bilateral lobectomies, and 1 bi-lobectomy. Twenty-four patients (69%) received adjuvant therapy. The overall cumulative 5 year survival was 91.5% (median overall survival = 45.5 months). Patients with a reference tumor <= 3 cm and SUV <= 3.1 had an expected 5-year survival of 100%. Patients with a reference tumor > 3 cm and SUV > 3.1 had an expected 5-year survival rate of 53.3%.SMPLC patients can benefit from aggressive surgery. The size and SUVmax of the reference tumor may predict postoperative outcomes. PMID- 26871769 TI - Circulating "LncPPARdelta" From Monocytes as a Novel Biomarker for Coronary Artery Diseases. AB - To investigate long noncoding RNA NONHSAT112178 (LncPPARdelta) as a biomarker for coronary artery disease (CAD) in peripheral blood monocyte cells, RT-qPCR was performed to validate the microarray results, receiver operating characteristic curve was applied to study the potential of LncPPARdelta as a biomarker. Diagnostic models from LncPPARdelta alone or combination of risk factors were constructed by Fisher criteria. The expression of genes neighboring the LncPPARdelta gene was examined with RT-qPCR in THP-1 cell line treated with LncPPARdelta siRNA. Using a diagnostic model by Fisher criteria, the consideration of risk factors increased the optimal sensitivity from 70.00% to 82.00% and decreased the specificity from 94.00% to 78.00%. The consideration of risk factors also increased area under the receiver operating characteristic curve from 0.727 to 0.785 (P = 0.001), from 0.712 to 0.768 (P = 0.01), and from 0.769 to 0.835 (P = 0.07), in the original, training, and test sets, respectively. Finally, we found that the expression of peroxisome proliferator activated receptor delta (PPARdelta), Adipose Differentiation-Related Protein (ADRP), and Angiopoietin-like 4 (ANGPTL4) were affected by LncPPARdelta silencing.Our present study indicated that LncPPARdelta, especially combined with risk factors, can be a good biomarker for CAD. LncPPARdelta regulates the expression of neighboring protein-coding genes, PPARdelta and its direct target genes ADRP and ANGPTL4. PMID- 26871770 TI - Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis: A Prospective Clinical Study. AB - Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity.Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders.A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021).Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID- 26871771 TI - Role of Pharmacogenetics in Improving the Safety of Psychiatric Care by Predicting the Potential Risks of Mania in CYP2D6 Poor Metabolizers Diagnosed With Bipolar Disorder. AB - One of the main concerns in psychiatric care is safety related to drug management. Pharmacogenetics provides an important tool to assess causes that may have contributed the adverse events during psychiatric therapy. This study illustrates the potential of pharmacogenetics to identify those patients for which pharmacogenetic-guided therapy could be appropriate. It aimed to investigate CYP2D6 genotype in our psychiatric population to assess the value of introducing pharmacogenetics as a primary improvement for predicting side effects.A broad series of 224 psychiatric patients comprising psychotic disorders, depressive disturbances, bipolar disorders, and anxiety disorders was included. The patients were genotyped with the AmpliChip CYP450 Test to analyzing 33 allelic variants of the CYP2D6 gene.All bipolar patients with poor metabolizer status showed maniac switching when CYP2D6 substrates such as selective serotonin reuptake inhibitors were prescribed. No specific patterns were identified for adverse events for other disorders.We propose to utilize pharmacogenetic testing as an intervention to aid in the identification of patients who are at risk of developing affective switching in bipolar disorder treated with selective serotonin reuptake inhibitors, CYP2D6 substrates, and inhibitors. PMID- 26871772 TI - Perioperative Computed Tomography Assessments of the Pancreas Predict Nonalcoholic Fatty Liver Disease After Pancreaticoduodenectomy. AB - Nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has become a clinically important issue. Although pancreatic exocrine insufficiency has been reported to be a main cause of NAFLD after PD, a clinically practical examination to assess the pancreatic exocrine function has not been established. The aim of this study was to evaluate risk factors for NAFLD after PD with a focus on perioperative computed tomography (CT) assessments of the pancreas.A retrospective review of 245 patients followed for more than 6 months after PD was conducted. We evaluated several pancreatic CT parameters, including the pancreatic parenchymal thickness, pancreatic duct-to-parenchymal ratio, pancreatic attenuation, and remnant pancreatic volume (RPV) on pre- and/or postoperative CT around 6 months after surgery. The variables, including the pancreatic CT parameters, were compared between the groups with and without NAFLD after PD.The incidence of NAFLD after PD was 19.2%. A multivariate analysis identified 5 independent risk factors for NAFLD after PD: a female gender (odds ratio [OR] 5.66, P < 0.001), RPV < 12 mL (OR 4.73, P = 0.001), preoperative pancreatic attenuation of <30 Hounsfield units (OR 4.50, P = 0.002), dissection of the right-sided nerve plexus around the superior mesenteric artery (OR 3.02, P = 0.017) and a preoperative serum carbohydrate antigen 19-9 level of >=70 U/mL (OR 2.58, P = 0.029).Our results showed that 2 pancreatic CT parameters, the degree of preoperative pancreatic attenuation and RPV, significantly influence the development of NAFLD after PD. Perioperative CT assessments of the pancreas may be helpful for predicting NAFLD after PD. PMID- 26871773 TI - Plasma and Synovial Fluid TrxR Levels are Correlated With Disease Risk and Severity in Patients With Rheumatoid Arthritis. AB - This study was designed and performed to establish the relationship between plasma and synovial fluid (SF) levels of thioredoxin reductase (TrxR) and disease activity in Chinese patients with rheumatoid arthritis (RA).This study consisted of a total of 224 patients diagnosed with RA, 224 age and sex-matched healthy controls, and 156 patient controls. The disease activity of RA patients was calculated as diseases activity score that include 28-joint counts (DAS 28), which was divided into low-diseases activity (LDA) and high-diseases activity (HDA) groups.Increased plasma TrxR was detected in patients with RA than healthy controls (P < 0.0001). With an area under the curve (AUC) of 0.874, plasma TrxR showed a evidently greater discriminatory ability than C-reactive protein (CRP; AUC, 0.815), antistreptolysin-O (ASO; AUC, 0.631), rheumatoid factor (RF, AUC, 0.793), and erythrocyte sedimentation rate (ESR, AUC, 0.789) in diagnosing RA. RA patients with HDA had significantly elevated TrxR levels in plasma and SF than did those with LDA (P < 0.0001). With an AUC of 0.874, plasma TrxR levels as an indicator for screening of HDA showed a significantly greater discriminatory ability than CRP (AUC, 0.690), ASO (AUC, 0.597), RF (AUC, 0.657), and ESR (AUC, 0.603). Similarly, SF TrxR levels as an indicator for screening of HDA also showed a significantly greater discriminatory ability as compared with above biomarkers.TrxR levels in plasma and SF were positively correlated with the severity of RA. TrxR levels may therefore serve as a new biomarker in addition of the traditional biomarkers for assessing the risk and severity of RA. Further analysis of TrxR release machinery may give us a new understanding of pathogenesis of RA. PMID- 26871775 TI - The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma: A Systematic Review and Meta-Analysis. AB - Effects of antiinterleukin 13 therapies in patients with asthma remain inconsistent. Therefore, we aimed to further clarify the efficacy and safety of antiinterleukin 13 therapies in adult asthmatics by a systematic review and meta analysis.Randomized controlled trials which reported pulmonary functions, fraction of exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ), rescue use of short-acting-beta-agonist (SABA), and rate of asthmatic exacerbation and adverse events were identified in Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), American College of Physician (ACP) Journal Club, and ISI Web of Science, reference lists and by manual searches. Randomized-effect models were used in meta-analysis to calculate pooled mean difference and relative risks (RR).Eight studies with 957 patients were enrolled. Systematic review showed that treatment with antiinterleukin 13 antibodies could significantly improve peak expiratory flow (PEF), decrease FeNO and asthmatic exacerbation, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. Two studies reported opposite results in reducing rescue use of SABA. Meta-analysis showed that antiinterleukin 13 monoclonal therapies could significantly decrease asthmatic exacerbation (RR 0.55, 95% CI: 0.31-0.96, z = 2.10, P = 0.04), but did not significantly improve the FEV1 (95% CI: -1.03 to 2.22, z = 0.72, P = 0.47) or increasing adverse events (RR 1.00, 95% CI: 0.91-1.10, z = 0.00, P = 1.00).Antiinterleukin 13 monoclonal therapies could be safely used to improve PEF, decrease FeNO and asthmatic exacerbation, and probably reduce rescue use of SABA, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. PMID- 26871774 TI - Comparison of the Efficacy and Safety of Different ACE Inhibitors in Patients With Chronic Heart Failure: A PRISMA-Compliant Network Meta-Analysis. AB - Heart failure is a public health problem and a great economic burden for patients and healthcare systems. Suppression of the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE)-inhibitors remains the mainstay of treatment for heart failure. However, the abundance of ACE inhibitors makes it difficult for doctors to choose.We performed this network meta-analysis of ACEIs in patients with heart failure in order to address this area of uncertainty.We searched PubMed, Embase, CENTRAL, and Medline.Any randomized controlled trial evaluating the efficacy and safety of captopril, enalapril, lisinopril, ramipril, or trandolapril or combined interventions of 2 or more of these drugs.Two reviewers extracted the data and made the quality assessment. At first, we used Stata software (version 12.0, StataCorp, College Station, TX) to make traditional pairwise meta-analyses for studies that directly compared different interventions. Then, network meta-analysis was performed using WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).A total of 29 studies were included. Lisinopril was associated with a higher rate of all-cause mortality compared with placebo (odds ratio 65.9, 95% credible interval 1.91 to 239.6) or ramipril (14.65, 1.23 to 49.5). Enalapril significantly reduced systolic blood pressure when compared with placebo (standardized mean differences -0.6, 95% credible interval -1.03 to -0.18). Both captopril (odds ratio 76.2, 95% credible interval 1.56 to 149.3) and enalapril (274.4, 2.4 to 512.9) were associated with a higher incidence of cough compared to placebo.Some important outcomes such as rehospitalization and cardiac death were not included. The sample size and the number of studies were limited, especially for ramipril.Our results suggest that enalapril might be the best option when considering factors such as increased ejection fraction, stroke volume, and decreased mean arterial pressure. However, enalapril was associated with the highest incidence of cough, gastrointestinal discomfort, and greater deterioration in renal function. Trandolapril ranked first in reducing systolic and diastolic blood pressure. Ramipril was associated with the lowest incidence of all-cause mortality. Lisinopril was the least effective in lowering systolic and diastolic blood pressure and was associated with the highest incidence of all-cause mortality. PMID- 26871777 TI - Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke: A Multimodal Magnetic Resonance Imaging Study. AB - The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores.Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients.These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke. PMID- 26871776 TI - Pretreatment Dynamic Contrast-Enhanced MRI Improves Prediction of Early Distant Metastases in Patients With Nasopharyngeal Carcinoma. AB - The identification of early distant metastases (DM) in patients with newly diagnosed, previously untreated nasopharyngeal carcinoma (NPC) plays an important role in selecting the most appropriate treatment approach. Here, we sought to investigate the predictive value of distinct MRI parameters for the detection of early DM.Between November 2010 and June 2011, a total of 51 newly diagnosed NPC patients were included. All of the study participants were followed until December 2014 at a single institution after completion of therapy. DM was defined as early when they were detected on pretreatment FDG-PET scans or within 6 months after initial diagnosis. The following parameters were tested for their ability to predict early DM: pretreatment FDG-PET standardized uptake value (SUV), MRI derived AJCC tumor staging, tumor volume, and dynamic contrast-enhanced (DCE) values. The DCE-derived ve was defined as the volume fraction of the extravascular, extracellular space.Compared with patients without early DM, patients with early DM had higher SUV, tumor volume, DCE mean (median) ve, ve skewness, ve kurtosis, and the largest mean ve selected among sequential slices (P < 0.05). No differences were identified when early DM were defined only according to the results of pretreatment FDG-PET. Among different quantitative DCE parameters, the mean ve had the highest area under curve (AUC, 0.765). However, the AUCs of SUV, tumor volume, mean ve, ve skewness, ve kurtosis, or the largest mean ve selected among the sequential slices did not differ significantly from one another (P = 0.82).Taken together, our results suggest that DCE-derived ve may be a useful parameter in combination with SUV and tumor volume for predicting early DM. Dynamic contrast-enhanced MRI may be complementary to FDG PET for selecting the most appropriate treatment approach in NPC patients. PMID- 26871778 TI - The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis. AB - Few randomized clinical trials have evaluated the efficacy of ginseng in patients with type 2 diabetes mellitus (T2DM). The current meta-analysis evaluated the ginseng-induced improvement in glucose control and insulin sensitivity in patients with type-2 diabetes or impaired glucose tolerance.Randomized clinical trials comparing ginseng supplementation versus control, in patients with T2DM or impaired glucose tolerance, were hand-searched from Medline, Cochrane, and Google Scholar databases by 2 independent reviewers using the terms "type 2 diabetes/diabetes/diabetic, impaired glucose tolerance, and ginseng/ginsenoside(s)." The primary outcome analyzed was the change in HbA1c, whereas the secondary outcomes included fasting glucose, postprandial glucose, fasting insulin, postprandial insulin, insulin resistance Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), triglycerides, total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL).Of the 141 studies identified, 8 studies were chosen for the current meta-analysis. The average number of patients, age, and sex distribution among the groups were comparable. Results reveal no significant difference in HbA1c levels between the ginseng supplementation and the control groups (pooled standardized difference in means = -0.148, 95% CI: -0.637 to 0.228, P = 0.355). Ginseng supplementation improved fasting glucose, postprandial insulin, and HOMA-IR levels, though no difference in postprandial glucose or fasting insulin was observed among the groups. Similarly, triglycerides, total cholesterol, and LDL levels showed significant difference between the treatment groups, while no difference in HDL was seen. In addition, ginseng-related therapy was ineffective in decreasing the fasting glucose levels in patients treated with oral hypoglycemic agents or insulin.The present results establish the benefit of ginseng supplementation in improving glucose control and insulin sensitivity in patients with T2DM or impaired glucose intolerance. PMID- 26871779 TI - Putaminal Diffusivity Correlates With Disease Progression in Parkinson's Disease: Prospective 6-Year Study. AB - Diffusion tensor imaging (DTI) is an increasingly used noninvasive imaging tool. However its long-term clinical utility is unclear. Parkinson's disease (PD) is a common neurodegenerative disease.We prospectively examined a cohort of 46 Parkinson's disease (PD) patients who underwent diffusion tensor imaging (DTI) of the brain at baseline and 6 years later on a 1.5 Tesla scanner using a standardized protocol. DTI parameters of mean diffusivity (MD) and fractional anisotrophy (FA) were extracted using regions-of-interest (ROIs) analysis from various brain regions.Compared to the baseline scan, MD increased in all brain regions (P < 0.0001). FA increased in the substantia nigra and posterior putamen, but decreased in the frontal white matter (P < 0.0001). Linear regression analysis demonstrated that the MD in the anterior putamen increased 11.6 units (95% CI = [4.71, 18.43]) (P = 0.0003) for every unit increase of United PD Rating Scale (UPDRS).Our 6-year prospective longitudinal study demonstrated increased diffusivity in all brain regions and that in the anterior putamen correlated with disease progression. Serial diffusion data may be useful as an additional objective in vivo biomarker for motor progression in PD. PMID- 26871780 TI - Low Response of Renin-Angiotensin System to Sodium Intake Intervention in Chinese Hypertensive Patients. AB - The interactions of sodium balance and response of renin-angiotensin-aldosterone system are important for maintaining the hemodynamic stability in physiological conditions. However, the influence of short-term sodium intake intervention in the response of renin-angiotensin system (RAS) on hypertensive patients is still unclear. Thus, we conducted a clinical trial to investigate the effects of short term sodium intake intervention on the response of RAS in hypertensive patients.One hundred twenty-five primary Chinese hypertensive patients were divided into high, moderate, and low sodium groups by 24-hour urinary sodium excretion (UNa). All the patients received a 10-day dietary sodium intake intervention with standardized sodium (173.91mmol/day) and potassium (61.53mmol/day). Blood pressure, urinary sodium, urinary potassium, plasma sodium, potassium, creatinine, the levels of plasma renin activity, plasma angiotensin II concentrations (AT-II), and plasma aldosterone concentrations were detected before and after the intervention.Before the intervention, no differences were found in blood pressure and RAS among 3 groups. After standardized dietary sodium intake intervention, both UNa excretion and systolic pressure decreased in high-sodium group, while they increased in moderate and low sodium groups. Intriguingly, there were no changes in the levels of plasma renin activity, AT-II, and plasma aldosterone concentrations among 3 groups during the intervention.The present study demonstrated that the influenced sodium excretion and blood pressure by short-term sodium intake intervention were independent of RAS quick response in Chinese hypertensive patients. PMID- 26871781 TI - Change of the Corticospinal Tract in the Unaffected Hemisphere by Change of the Dominant Hand Following Stroke: A Cohort Study. AB - We investigated the change of the corticospinal tract (CST) in the unaffected hemisphere by the change of the dominant hand in stroke patients, using diffusion tensor tractography (DTT).Forty-eight stroke patients with right-hand dominance were recruited. The patients were assigned to 3 groups: group A (12 patients) right-hand dominance was maintained after the right-hand weakness, group B (17 patients)-right-hand dominance changed to the left-hand dominance after the right hand weakness, and group C (19 patients)-right-hand dominance was maintained after the left-hand weakness had developed. The function of the unaffected upper extremity was evaluated using the grip strength (GS), Manual Function Test (MFT), Purdue Pegboard Test (PPT), and modified Barthel Index (MBI). DTT was performed twice (1st DTT, 2nd DTT), and the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and voxel number (VN) of the CST in the unaffected hemisphere were measured.In group B, the VN on 2nd DTT was significantly increased compared with the 1st DTT, and all other clinical data (GS, MFT, PPT, and MBI) showed a significant increase between 1st and 2nd DTT (P < 0.05). The change of the VN showed moderate correlation with the change of the GS (r = 0.499, P < 0.05), PPT (r = 0.531, P < 0.05), and MBI (r = 0.551, P < 0.05).We found that the fiber number of the CST in the unaffected hemisphere was increased by the change of the dominant hand in stroke patients. We believe that our results have important implications in terms of neurorehabilitation. PMID- 26871783 TI - Injury of the Ascending Reticular Activating System in Patients With Fatigue and Hypersomnia Following Mild Traumatic Brain Injury: Two Case Reports. AB - We report on patients with post-traumatic fatigue and hypersomnia who showed injury of the lower portion of the ascending reticular activating system (ARAS) between the pontine reticular formation (RF) and the intralaminar thalamic nucleus (ILN) following mild traumatic brain injury (TBI), using diffusion tensor tractography (DTT).Two patients with mild TBI resulting from a car accident were enrolled in this study. Patient 1 was a 51-year-old woman showed abnormalities as 6.9 (cut off: 3.7 points) and 18 (cut off: 10) on the Fatigue Severity Scale and the Epworth Sleepiness Scale at 11 months after onset. Patient 2 was a 64-year old woman who revealed abnormalities on the Fatigue Severity Scale and the Epworth Sleepiness Scale with 6.8 and 19 at 3 months after onset.In both patients, the upper ARAS in which the neural connectivity of the ILN to the cerebral cortex did not show significant abnormalities. However, we observed the narrowing of the left dorsal lower ARAS between the pontine RF and the ILN in both patients and the tearing (patient 1) and narrowing (patient 2) of the left ventral lower ARAS between the pontine RF and the hypothalamus.Injuries of the dorsal and ventral lower ARAS were demonstrated in patients with fatigue and hypersomnia following mild TBI. We believe that these injuries of the ARAS might be a pathogenetic mechanism of fatigue and hypersomnia in patients with TBI. PMID- 26871782 TI - Tumor Vascular Permeability Pattern Is Associated With Complete Response in Immunocompetent Patients With Newly Diagnosed Primary Central Nervous System Lymphoma: Retrospective Cohort Study. AB - A dynamic contrast-enhanced MR imaging (DCE-MRI) could provide the information about tumor drug delivery efficacy. We investigated the potential utility of the permeability pattern of DCE-MRI for predicting tumor response to high dose methotrexate treatment and progression-free survival (PFS) in patients with primary CNS lymphoma (PCNSL). Clinical and conventional imaging parameters were assessed as potential predictors of tumor response in 48 immunocompetent PCNSL patients in a preliminary study. Fifty additional immunocompetent patients (27 men and 23 women; mean age, 60.6 years) with PCNSL underwent DCE-MRI before starting first-line treatment with high dose-methotrexate. The DCE-MRI pattern was categorized as diffuse or nondiffuse. After 4 courses of high dose methotrexate, patients underwent follow-up brain MR imaging to identify their complete response (CR). Predictors of CR and PFS were analyzed using clinical parameters, conventional MRI, and DCE-MRI. CR was noted in 20 (74.1%) of 27 patients with diffuse DCE-MRI pattern and in 4 (17.4%) of 23 patients with nondiffuse DCE-MRI pattern. The diffuse DCE-MRI pattern showed a significantly higher association with CR than the nondiffuse pattern (P < 0.001). Multivariate Cox proportional hazards model revealed that the DCE-MRI pattern (hazard ratio = 0.70; P = 0.045), age (hazard ratio = 1.47; P = 0.041), and adjuvant autologous stem-cell transplantation (hazard ratio = 6.97; P = 0.003) tended to be associated with a PFS. The pretreatment diffuse DCE-MRI pattern can be used as a potential imaging biomarker for predicting CR and a longer PFS in patients with newly diagnosed PCNSLs. PMID- 26871784 TI - A Case Report of Late Onset Mania Caused by Hyponatremia in a Patient With Empty Sella Syndrome. AB - Recurrent manic-like episodes can be induced by hyponatremia possibly due to empty sella syndrome. In the present case, the patient was proven to have syndrome of inappropriate antidiuretic hormone (SIADH) secretion with manic symptoms that resolved after the normalization of the plasma sodium level.To our knowledge, this is the first case of hyponatremia-induced manic symptoms in a patient with empty sella syndrome. More attention should be paid to late-onset mania, because it may be the sign of a more serious medical problem. PMID- 26871785 TI - High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT. AB - Tumor-associated macrophages (TAMs) are associated with poor prognosis in numerous human cancers and play important roles in tumor progression. Epithelial mesenchymal transition (EMT) contributes to invasion and metastasis in cancer. However, the associations between TAMs and EMT are not clear in gastric cancer (GC). The present study was designed to investigate the effects of TAMs on EMT in human GC.TAMs marker CD68 and EMT-related proteins were detected by immunohistochemistry (IHC) in human GC tissues and their clinical significance were evaluated.A high level of infiltration of TAMs was associated with aggressive characteristics of tumor and an independent poor prognostic factor in human GC tissues. Infiltration of TAMs was also associated with EMT-related proteins in human GC tissues.Our findings suggest that the high level of infiltration TAMs was associated with aggressive features of GC and is an independent poor prognostic factor in GC patients. TAMs are associated with EMT induction in human GC tissues. The level of TAMs infiltration may be used as a prognostic factor and even a therapeutic target in GC. PMID- 26871786 TI - Upregulation of miRNA-130a Represents Good Prognosis in Patients With HBV-Related Acute-on-Chronic Liver Failure: A Prospective Study. AB - Prompt and accurate prediction of the outcome is the key to make correct medical decision and to reduce the mortality in patients with HBV-related acute-on chronic liver failure (ACLF). Increasing evidence have certified that small, noncoding microRNAs (miRNAs) play critically regulatory roles in the pathogenesis of liver diseases. However, it remains unclear whether and how miRNAs involve in the prognosis of ACLF.Microarray analysis was performed to characterize the miRNA expression profiles in liver tissues from 1 HBV-related ACLF patient and 1 matched healthy control. Nine miRNAs with at least 5 folds difference between these 2 persons were picked out. The present prospective study involving 39 HBV related ACLF patients including 20 recovered and 19 nonrecovered patients, which include death (n = 9) and liver transplantation (n = 10). The serum expression of these miRNAs detected by quantitative real-time Polymerase Chain Reaction (qRT RCR) was then compared between the 2 groups. Moreover, the correlation between the serum miRNAs and the prognostic indexes for ACLF was analyzed.The result of microarray analysis showed 9 miRNAs had different expression in liver tissues of ACLF patient compared with healthy control (upregulated: miRNA-130a, -21, -143, and -200a; downregulated: miRNA-486-5p, -192, -148a, -122, and -194). Unlike the expression profiles in liver tissue, 8 serum miRNAs except miRNA-194 were markedly upregulated in ACLF patients (P < 0.05). Remarkably, the serum expression of miRNA-130a and miRNA-486-5p was higher in recovered than nonrecovered ACLF patients (P < 0.05). Especially, the serum miRNA-130a was negatively correlated with international normalized ratio, prothrombin time, Model for End-Stage Liver Disease score, and positively correlated with prothrombin time activity. The AUC for recovered versus nonrecovered patients of miRNA-130a was 0.741 (P = 0.02).miRNA-130a might be a useful prognosis biomarker in patients with HBV-related ACLF. PMID- 26871788 TI - Effect of Weekend Admissions on the Treatment Process and Outcomes of Internal Medicine Patients: A Nationwide Cross-Sectional Study. AB - Many studies address the effect of weekend admission on patient outcomes. This population-based study aimed to evaluate the relationship between weekend admission and the treatment process and outcomes of general internal medicine patients in Taiwan.A total of 82,340 patients (16,657 weekend and 65,683 weekday admissions) aged >=20 years and admitted to the internal medicine departments of 17 medical centers between 2007 and 2009 were identified from the Taiwan National Health Insurance Research Database. A generalized estimating equation (GEE) analysis was used to compare patients admitted on weekends and those admitted on weekdays.Patients who were admitted on weekends were more likely to undergo intubation (odds ratio [OR]: 1.27; 95% confidence interval [CI]: 1.16-1.39; P < 0.001) and/or mechanical ventilation (OR, 1.25; 95% CI, 1.15-1.35; P < 0.001), cardio-pulmonary resuscitation (OR: 1.45; 95% CI: 1.05-2.01; P = 0.026), and be transferred to the intensive care unit (ICU) (OR: 1.16; 95% CI: 1.03-1.30; P = 0.015) compared with those admitted on weekdays. Weekend-admitted patients also had higher odds of in-hospital mortality (OR: 1.19; 95% CI: 1.09-1.30; P < 0.001) and hospital treatment cost (OR: 1.04; 95% CI: 1.01-1.06; P = 0.008) than weekday admitted patients.General internal medicine patients who were admitted on weekends experienced more intensive care procedures and higher ICU admission, in hospital mortality, and treatment cost. Intensive care utilization may serve as early indicator of poorer outcomes and a potential entry point to offer preventive intervention before proceeding to intensive treatment. PMID- 26871789 TI - Transverse Stress Fracture of the Proximal Patella: A Case Report. AB - Among stress fractures associated with sports activities, patellar stress fracture is rare. Regarding patella stress fractures, so far only distal transverse or lateral longitudinal fractures have been reported, but there are no reports of transverse fractures occurring in the proximal patella. We describe an extremely rare case of transverse stress fracture of proximal patella in a 9-year old athlete.A 9-year old boy, who participated in sports (sprints and Kendo) presented with left knee pain without any external injury. In plain radiographs, a fracture line was observed in the proximal 1/3 of the left patella, and a patella stress fracture was diagnosed. For treatment, because 7 months of conservative therapy showed no improvement, internal fixation was carried out using Acutrak screws, and bone union was thus achieved. Three months after the operation, he was able to return to his previous level of athletic sports activity.Regarding the mechanism of onset, it is believed that the causes are longitudinal traction force and patellofemoral contact pressure. On the other hand, the contact region of the patella with the femur changes with the flexion angle of the knee. In the current case, the fracture occurred at a site where the patella was in contact with the femur at a flexion angle of >90 degrees , so it is believed that it occurred as a clinical condition from being subjected to repeated longitudinal traction force and patellofemoral contact pressure at a flexion angle of >90 degrees , during the sports activities of sprints and Kendo. The nonunion of the transverse stress fracture of his proximal patella was successfully treated with internal fixation using Acutrak screws. PMID- 26871787 TI - Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study. AB - The implications of low triiodothyronine syndrome (LT3S) in patients with radiation enteritis (RE) have not been properly investigated. As such, we conducted this cohort study to investigate the association between LT3S and RE, to explore the etiology of LT3S in RE, to evaluate the clinical features and clinical outcomes of LT3S patients, and to inspect the correlation of clinical variables and LT3S in RE.This prospective study included 39 RE patients. Medical records and various laboratory parameters (including thyroidal, tumorous, nutritional, and radiotherapy variables) were collected in all participants.Our results showed that the incidence of LT3S was 84.6% in patients with RE. Total protein (71.7 +/- 5.7 vs 63.2 +/- 9.6 g/L, P = 0.04) and albumin (ALB, 46.0 +/- 4.6 vs 38.7 +/- 5.3 g/L, P = 0.01) were significantly lower in LT3S group compared with those in euthyroid group. Standard thyroid-stimulating hormone index (-0.89 +/- 2.11 vs -2.39 +/- 1.33, P = 0.03) and sum activity of deiodinases (19.74 +/- 4.19 vs 12.55 +/- 4.32 nmol/L, P = 0.01) were significantly lower in LT3S group. Patients with LT3S suffered longer duration of hospitalization (48.25 +/- 23.29 days in LT3S vs 26.75 +/- 10.56 days in euthyroid, P = 0.036). Low serum ALB (beta = 0.694, 95% CI = 0.007-0.190, P = 0.037) was the only significant predictor of LT3S.LT3S was common in RE patients. A hypodeiodination condition and a potential pituitary-thyrotroph dysfunction might play a role in the pathophysiology of LT3S in RE. Worse nutritional status and clinical outcomes were confirmed in RE patients with LT3S. Furthermore, total protein and ALB were observed as protective and differentiating parameters of LT3S in RE. In summary, this was the 1st investigation to evaluate the clinical correlation between RE and LT3S, investigate the prevalence of LT3S in RE, and explore the pathogenesis of LT3S, despite the limitation of a relatively small sample size. These results will hopefully encourage future research to place greater emphasis on early identification of LT3S in RE patients. PMID- 26871791 TI - A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI: Correlation With Immunity and Immune Reconstitution. AB - The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect.A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status.The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings.No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm (3.00-52.00 cells/mm) in group 1 and 42.00 cells/mm (10.00-252.00 cells/mm) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021).Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy. PMID- 26871790 TI - Folic Acid and Vitamins D and B12 Correlate With Homocysteine in Chinese Patients With Type-2 Diabetes Mellitus, Hypertension, or Cardiovascular Disease. AB - Elevated serum homocysteine has been shown to be a risk factor for hypertension, cardiovascular disease (CVD), and type-2 diabetes mellitus (T2DM).We characterized the relationships between the serum levels of homocysteine, folic acid, and vitamins D2, D3, and B12 in patients with T2DM, CVD, and hypertension in Shanghai, China. The levels of these serum biochemical markers were determined for 9311 Chinese patients (mean age: 79.50 +/- 13.26 years) with T2DM (N = 839), hypertension (N = 490), or CVD (N = 7925). The demographic and serum biochemical data were compared using an analysis of variance. We performed stratified analyses using Pearson linear regression to investigate correlations between the different variables in the T2DM, CVD, and hypertension groups and in patients aged < 50, 50 to 64, 65 to 80, and >=80 years. A subgroup analysis was also performed to identify correlations between the serum biochemical markers. Stratified chi-squared analyses were performed based on the levels of folic acid and total vitamin D.In all 3 patient groups, elevated levels of vitamin D2 and homocysteine were observed, whereas the levels of folic acid and vitamins D3 and B12 were lower than the reference range for each serum marker (P < 0.05 for all). The linear regression and stratified analyses showed that the highest levels of folic acid and vitamins D2 and D3 correlated with the lowest level of homocysteine in T2DM, CVD, and hypertension patients (P < 0.05 for all), whereas the highest level of vitamin B12 correlated with a lowest level of homocysteine in CVD patients only (P < 0.05).Our results indicate that the contributions of both vitamin D2 and vitamin D3 should be considered in investigations of the effects of vitamin D supplements in T2DM, CVD, and hypertension patients. Our findings warrant future studies of the benefits of vitamin D and folic acid supplements for reducing the risk of T2DM, CVD, and hypertension in elderly Chinese people, as well as the benefits of vitamin B12 supplements for reducing the risk of CVD alone. PMID- 26871792 TI - Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty: A Nationwide Cohort Study. AB - Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery.A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n = 270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow up time was 10 years (range, 7-21).The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events.During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11).Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls. PMID- 26871793 TI - Plexiform Neurofibroma: A Case Report. AB - Plexiform neurofibromas represent an uncommon variant (30%) of neurofibromatosis type 1 (NF-1) in which neurofibromas arise from multiple nerves as bulging and deforming masses involving also connective tissue and skin folds.We report a rare case of a 30-year-old man who presented with a progressive facial deformity that began in early childhood. Skin examination also revealed multiple neurofibromas and cafe-au-lait macules on the trunk and arms. Histopathological examination on biopsy samples showed overgrowth of peripheral nerve components and connective tissue. Two diagnostic criteria for NF-1 (plexiform variant) were met, the patient did not accept to undergo genetic testing. Craniofacial MRI confirmed the presence of a deforming mass arising from the left side of his face giving homolateral eye dislocation.Surgery is the mainstay of the treatment. However, the patient expressed the preference to avoid surgery and chose to undergo clinical follow-up every 6 months.Diagnosis of plexiform neurofibromas is usually made clinically, especially if classical hallmarks of NF-1 are present. Therapy is surgical, aiming at resecting deforming masses and cancerous tissue when malignant transformation occurs. PMID- 26871794 TI - The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial. AB - The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4 T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01B_3 and control group ( 0.096 log10 copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4 T-cell count, ART initiation, or HIV related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4 T-cells, but had no significant impact on F4-specific CD8 T-cell and anti-F4 antibody levels.F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4 T-cell responses, but did not reduce HIV-1 VL, impact CD4 T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID- 26871795 TI - The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma: A Retrospective Chinese Cohort Study. AB - The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126-0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT. PMID- 26871796 TI - Optical Coherence Tomography Assessment Before and After Vitamin Supplementation in a Patient With Vitamin A Deficiency: A Case Report and Literature Review. AB - Vitamin A is an essential fat-soluble vitamin important for the function of various body systems. In the eye, vitamin A is essential for the synthesis of visual pigments in photoreceptors. Vitamin A deficiency is a rare condition in the developed countries and might follow bariatric or intestinal bypass surgery.We present the case of a 67-year-old male that complained of visual loss and nyctalopia. Patient had bariatric surgery 15 years before for weight loss. Low serum levels of vitamin A confirmed the diagnosis and patient started vitamin A supplementation. Visual fields, macular thickness, and ganglion cell layer thickness were recorded and monitored 1 month, 6 months, and 1 year after the beginning of therapy. Visual fields were significantly altered and central macular thickness and ganglion cell layer thickness were reduced, but the first 2 showed a significant recovery with vitamin supplementation therapy. By the 1st month of treatment patient referred a complete remission of visual symptoms. Further, we observed hyperreflective material accumulating beneath a partially disrupted ellipsoid band in the high definition optical coherence tomography that also improved progressively with vitamin repletion.Newer and more sophisticated imaging systems have increased our knowledge of the mechanisms responsible for retinal diseases. To our knowledge, this is the first description of the effect of vitamin A deficiency and vitamin supplementation on macular thickness. This case also highlights the importance of considering bariatric bypass surgery as a cause of vitamin A deficiency in developed countries. PMID- 26871797 TI - Effects of Heart Bypass Surgery on Plasma Abeta40 and Abeta42 Levels in Infants and Young Children. AB - Accumulation of beta-amyloid (Abeta) plaques is a pathological hallmark of Alzheimer disease. Abeta levels in animals and adults were reported to be associated with postoperative cognitive dysfunction (POCD). Our goal was to determine the plasma levels of Abeta in infants and young children after cardiac surgery with cardiopulmonary bypass (CPB).Forty-two infants and young children aged from 1 to 35 months undergoing cardiac surgery with general anesthetics were prospectively enrolled from January to June 2014 at a tertiary medical center. Perioperative plasma samples were obtained, and Abeta42 and Abeta40 levels were measured using ELISA. Other clinical characteristics of the patients were also recorded.Plasma levels of Abeta42 and Abeta40 decreased dramatically 2 hours after surgery and remained significantly lower 6 hours after operation. Baseline Abeta42 level correlated significantly with surgical intensive care unit (SICU) length of stay (LOS) and was an independent predictor for SICU LOS on multivariate analysis.Cardiac surgery with CPB decreases plasma Abeta levels. Plasma levels of Abeta42 and Abeta40 might be used as novel biomarkers for predicting outcomes in the patient population. PMID- 26871799 TI - Preoperative Neutrophil-to-lymphocyte Ratio Predicts Long-term Survival in Patients Undergoing Total Laryngectomy With Advanced Laryngeal Squamous Cell Carcinoma: A Single-center Retrospective Study. AB - There is increasing evidence that the neutrophil-to-lymphocyte ratio (NLR) is a stage-independent predictor of poor outcome in patients with cancer. The purpose of this study was to investigate the association between cancer-specific survival (CSS), overall survival (OS), and the preoperative NLR in patients with advanced laryngeal squamous cell carcinoma (LSCC) undergoing total laryngectomy (TL).All patients with a new diagnosis of advanced laryngeal cancer (stages III and IV) presenting at the Department of Head and Neck Oncology, Sun Yat-sen University Cancer Center between January 1990 and July 2010 (n = 420) were included. To evaluate the independent prognostic relevance of the NLR, univariate and multivariate Cox regression models were used. CSS and OS were estimated using the Kaplan-Meier method.Four-hundred twenty patients were enrolled in this study. Patients with an NLR >=2.59 showed a significantly lower CSS (P = .014) and OS (P = .032) than patients with an NLR <2.59. The Cox proportional multivariate hazard model showed that a higher preoperative NLR was independently correlated with a poor CSS and OS, with hazard ratios of 1.42 (95% confidence interval [CI] 1.06 1.91, P = .018) and 1.31 (95% CI 1.00-1.71, P = .046), respectively.The NLR may be an independent prognostic marker for CSS and OS in patients with advanced LSCC undergoing TL. PMID- 26871800 TI - Management of Postoperative Pain in Medical Institutions in Shandong Province in China. AB - The aim of the study was to investigate current situation of postoperative pain management in medical institutions in Shandong Province.A questionnaire was developed on the basis of guidelines of acute pain and pain quality assessment scale. The questionnaire was used to obtain information regarding the nature and scale of the medical institution, structure of pain management organization, implementation of pain assessment, and analgesic techniques and processes used in clinical practice. A multistage stratified and cluster sampling method was employed to investigate the current situation of postoperative pain management in 168 medical institutions in Shandong Province.For acute pain service (APS), 32% of the hospitals established postoperative pain management organizations similar to APS. For pain evaluation, 57.1% of the hospitals evaluated pain as the fifth vital sign, and 47.0% of the hospitals evaluated pain at rest and during activity. Furthermore, 43.0% of the surveyed hospitals employed patient controlled analgesia mode, of which hospitals employing brachial plexus block, lumbar plexus block, and femoral nerve block analgesia accounted for 5.0%, 1.0%, and 4.0%, respectively. The survey revealed that 51.0% of the hospitals educated patients about pain and pain management, of which patients were postoperatively educated by ward nurses in 5.0% and patients were educated by APS during ward rounds in 2.0%.There is a lack of standardized postoperative pain management, the involvement of nurses in pain management is scarce, and the pain assessment and education and application of advanced analgesic management techniques were found to be inadequate in medical institutions in Shandong Province. PMID- 26871798 TI - Hepatitis C Virus Subtype and Evolution Characteristic Among Drug Users, Men Who Have Sex With Men, and the General Population in Beijing, China. AB - The aim of this study was to characterize the current molecular epidemiology of hepatitis C virus (HCV) infection and evaluate the evolutionary patterns of HCV subtypes in Beijing, China, among different subpopulations.The whole blood samples and behavioral data were collected from a total of 10,354 subjects, including drug users (DUs), men who have sex with men (MSM), and the general population, in Beijing from 2010 to 2011. Samples were tested for HCV infection using both enzyme-linked immunosorbent assay (ELISA) and real-time PCR. All viremic subjects were then sequenced by nested PCR over core/E1 and NS5B regions. Phylogenetic and phylogeographic analysis was performed by BEAST software.In total, 217 subjects (2.1%) were tested positive for HCV by antibody or vRNA-based testing. HCV prevalence rates for DUs, MSM, and the general population were 26.2%, 0.54%, and 0.37%, respectively. The 156 HCV RNA-positive samples were sequenced. Nine HCV genotypes, including 1a, 1b, 2a, 3a, 3b, 6a, 6n, 6u and 6v, were detected. The most prevalent subtypes were 3b (36.09%), 1b (32.54%), and 3a (16.57%). Bayesian evolutionary analysis estimated that the time of introduction of subtype 1b into Beijing was 2004 (95% CI: 1997.7, 2007.7), with subtypes 3a and 3b being introduced later in 2006. Evolutionary analyses further suggested that subtype 1b from Beijing and Shanghai were closely related, whereas subtype 3a sequences were more similar with sequences from Yunnan, Guangzhou, Hong Kong, and Jiangsu. Subtype 3b sequences were closely related to those from Yunnan, Guangdong, and Hong Kong.Thus, the current HCV epidemic in Beijing is complex, heavily affecting DUs, and involving multiple genotypes that likely spread from different regions in China with its large migrant population. PMID- 26871801 TI - Association of Megsin Gene Variants With IgA Nephropathy in Northwest Chinese Population: A STROBE-Compliant Observational Study. AB - Megsin is a mesangial cell-predominant gene that encodes a serpin family protein which is expressed in the renal mesangium. Overexpression of megsin has been observed in the glomeruli of patients with IgA nephropathy (IgAN). The aim of this study was to evaluate the association of megsin polymorphisms (rs1055901 and rs1055902) with IgAN in a Chinese population.We examined 351 patients with histologically proven IgAN and compared them with 310 age, sex, and ethnicity matched healthy subjects. Two single nucleotide polymorphisms (SNPs) in megsin were genotyped by Sequenom MassARRAY. SPSS 18.0 was used for statistical analyses, and SNP Stats to test for associations between these polymorphisms and IgAN risk. Odds ratios with 95% confidence intervals were used to assess the relationships.We found that rs1055901 and rs1055902 SNPs were not correlated with susceptibility to IgAN in Northwest Chinese population. Analyses of the relationship between genotypes and clinical variables indicated that in patients with IgAN, rs1055901 was associated with 24-hour proteinuria, an increase in blood pressure, and Lee's grade (P = 0.04, 0.02, and 0.04, respectively), and rs1055902 was associated with 24-hour proteinuria and Lee's grade (P = 0.03 and 0.01, respectively). However, the results showed no association between these gene variants and sex of the patients.These results indicate that megsin gene variants may play a role in the severity, development, and/or progression of IgAN in Northwest Chinese population. PMID- 26871802 TI - Complementary and Alternative Medicine Treatment Options for Otitis Media: A Systematic Review. AB - Otitis media (OM) has numerous presentations in children. Together with conventional medical therapies aimed to prevent and/or treat OM, a rising number of complementary and alternative medicine (CAM) treatment options can be offered. Since OM is common in children, parents may ask healthcare professionals about possible CAM therapies. Many physicians feel that their knowledge is limited regarding these therapies, and that they desire some information. Therefore, we conducted a literature review of CAM therapies for OM, taking into account that many of these treatments, their validity and efficacy and have not been scientifically demonstrated.We performed a search in MEDLINE (accessed via PubMed) using the following terms: "CAM" in conjunction with "OM" and "children. Retrieved publications regarding treatment of OM in children which included these terms included randomized controlled trials, prospective/retrospective studies, and case studies.The following CAM options for OM treatment in children were considered: acupuncture, homeopathy, herbal medicine/phytotherapy, osteopathy, chiropractic, xylitol, ear candling, vitamin D supplement, and systemic and topical probiotics. We reviewed each treatment and described the level of scientific evidence of the relevant publications.The therapeutic approaches commonly associated with CAM are usually conservative, and do not include drugs or surgery. Currently, CAM is not considered by physicians a potential treatment of OM, as there is limited supporting evidence. Further studies are warranted in order to evaluate the potential value of CAM therapies for OM. PMID- 26871803 TI - The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality. AB - The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC.We followed up 51,164 participants (aged 44-94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC.During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08-4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10-3.34). Both never smokers (HR, 0.46; 95% CI, 0.32-0.65) and quitters (HR, 0.62; 95% CI, 0.39-0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18-0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis. PMID- 26871804 TI - Changes in Plasma Adiponectin Concentrations in Patients With Hemorrhagic Fever With Renal Syndrome: An Observational Prospective Study. AB - The objective is to observe the changes in plasma adiponectin (APN) and its predictive capacity for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS).One hundred and five patients who were treated at our center between October 2011 and December 2012 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group, and a critical-type group according to the HFRS criteria for clinical classification. Ninety-three plasma samples from the patients in the acute stage and 78 samples from the patients in the convalescent stage were obtained, and 28 samples from healthy subjects were obtained as controls. The concentrations of APN were detected using the enzyme-linked immunosorbent assay. The levels of white blood cells, platelets, hematocrit, albumin, blood urea nitrogen, serum creatinine, and uric acid in the samples were routinely tested. The levels of APN among the different types were compared; the correlation between APN and the laboratory parameters was analyzed. The predictive effectiveness for prognosis of APN and the laboratory parameters as mentioned above were evaluated using the receiver operating characteristic curve analysis.The levels of APN in the mild- and moderate-type patients in the acute stage were significantly higher than the severe-type and control (P < 0.05) and decreased with the severity of the disease, while there were no obvious difference among severe-, critical-type and control groups. The levels of APN in patients in the convalescent stage were higher than the control group (P < 0.05), and the APN levels of the critical-type group were higher compared with the mild type groups (P < 0.05). Adiponectin was negatively correlated with white blood cells and hematocrit and positively correlated with platelets, albumin, and uric acid (P < 0.001). Adiponectin showed no statistical significance for predicting prognosis, with the area under the curve equal to 0.609 (95% CI: 0.237-0.745, P = 0.215).Adiponectin can be considered as a novel biomarker for disease severity in patients with HFRS, while it seems to have no predictive capacity for prognosis of HFRS. PMID- 26871806 TI - Multiple Stent Fractures After Everolimus-Eluting Stent Implantation Causing Acute Myocardial Infarction: A Case Report. AB - Stent fracture is an uncommon complication of drug-eluting stent implantation, but it has a clinical significance because of its potential association with adverse cardiac events such as in-stent restenosis, target lesion revascularization, and stent thrombosis. Multiple stent fractures account for a small proportion, but they may lead to more serious complications. Newer generation drug-eluting stents are designed for improved safety and efficacy compared with early generation drug-eluting stents. Multiple stent fractures after newer generation drug-eluting stent implantation are a rare case.We report a case of 25-year-old male who presented with acute myocardial infarction caused by multiple stent fractures after everolimus-eluting stents implantation and was treated by balloon angioplasty.Physicians should be aware of the possibility of multiple stent fractures even after newer generation drug-eluting stent implantation. PMID- 26871805 TI - Low-Dose Ketamine Pretreatment Reduces the Incidence and Severity of Myoclonus Induced by Etomidate: A Randomized, Double-Blinded, Controlled Clinical Trial. AB - Myoclonic movement induced by etomidate is a common but undesirable problem during general anesthesia induction. To investigate the influence of pretreatment with low-dose ketamine on the incidence and severity of myoclonus induced by etomidate, 104 patients were randomized allocated to 1 of 2 equally sized groups (n = 52) to receive either intravenous low-dose ketamine 0.5 mg/kg (group K) or an equal volume of normal saline (group S) 1 minute before induction of anesthesia with 0.3-mg/kg etomidate. The incidence and severity of myoclonus were assessed for 2 minutes after administration of etomidate. Here, we found that the incidence and intensity of myoclonus were both significantly reduced in low-dose ketamine-treated group compared with saline-treated group. The incidence of adverse effects was low and similar between groups. These results demonstrate that intravenous infusion of low-dose ketamine 0.5 mg/kg 1 minute prior to etomidate administration is effective in relieving etomidate-induced myoclonic movements during general anesthesia induction. PMID- 26871807 TI - The Impact of Emergency Physician Seniority on Clinical Efficiency, Emergency Department Resource Use, Patient Outcomes, and Disposition Accuracy. AB - The ability of emergency physicians (EPs) to continue within the specialty has been called into question due to high stress in emergency departments (EDs).The purpose of this study was to investigate the impact of EP seniority on clinical performance.A retrospective, 1-year cohort study was conducted across 3 EDs in the largest health-care system in Taiwan. Participants included 44,383 adult nontrauma patients who presented to the EDs. Physicians were categorized as junior, intermediate, and senior EPs according to <=5, 6 to 10, and >10 years of ED work experience. The door-to-order and door-to-disposition time were used to evaluate EP efficiency. Emergency department resource use indicators included diagnostic investigations of electrocardiography, plain film radiography, laboratory tests, and computed tomography scans. Discharge and mortality rates were used as patient outcomes. Disposition accuracy was evaluated by ED revisit rate.Senior EPs were found to have longer door-to-order (11.3, 12.4 minutes) and door-to-disposition (2, 1.7 hours) time than nonsenior EPs in urgent and nonurgent patients (junior: 9.4, 10.2 minutes and 1.7, 1.5 hours; intermediate: 9.5, 10.7 minutes and 1.7, 1.5 hours). Senior EPs tended to order fewer electrocardiograms, radiographs, and computed tomography scans in nonurgent patients. Adjusting for age, sex, disease acuity, and medical setting, patients treated by junior and intermediate EPs had higher mortality in the ED (adjusted odd ratios, 1.5 and 1.6, respectively).Compared with EPs with <=10 years of work experience, senior EPs take more time for order prescription and patient disposition, use fewer diagnostic investigations, particularly for nonurgent patients, and are associated with a lower ED mortality rate. PMID- 26871809 TI - Classic Case Report of Donohue Syndrome (Leprechaunism; OMIM *246200): The Impact of Consanguineous Mating. AB - Donohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births). We discuss how the disease presents, its genetic underpinning, and its prevention.The case was encountered in an Arab male born on 1 September, 2014, for consanguineous parents. The delivery was via cesarean section at 37 weeks gestation due to severe intrauterine growth restriction and nonprogress labor term. The patient was admitted to the Neonatal Intensive Care Unit due to infection, and jaundice. Dysmorphic features, abnormalities of the craniofacial region, low birth weight, skin abnormalities, abdominal distension and hypertrichosis were observed. Laboratory examinations showed, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anemia.The diagnosis of DS was done based on the combinations of typical dysmorphic characteristics, clinical evaluation, supported by genetic analysis and exaggerated biochemical results. Genetic diagnosis of DS was performed through analysis of DNA via polymerase chain reaction (PCR). A qualitative real time PCR was used, to monitor the amplification of a targeted DNA molecule during the PCR. Other technique using sequencing of the INSR gene, which permits genetic diagnosis, counseling, and antenatal diagnoses in subsequent pregnancies, were also performed.Treatment of DS is supportive and requires the combined efforts of a multidisciplinary team, which include pediatricians, endocrinologists, dermatologists, and other health care professionals. Currently, treatment with recombinant insulin-like growth factor 1 demonstrates effectiveness, and a combination treatment with insulin-like growth factor binding protein 3 resulted in an increased lifespan.There is a scarcity of genetic information on DS among the Arab population. Consanguinity is one of underlying reasons for the appearance of rare genetic disorders. Inbreeding has long been considered a controversial phenomenon. Genetic counseling and overwhelming the alertness of the negative consequences of consanguinity on public health are warranted. PMID- 26871810 TI - TNM Staging of Colorectal Cancer Should be Reconsidered According to Weighting of the T Stage: Verification Based on a 25-Year Follow-Up. AB - The gradient monotonicity of existing tumor, node, metastases staging systems for colorectal cancer is unsatisfactory. Our proposed T-plus staging system strengthens weighting of the T stage. In this study, applicability of the T-plus staging system was verified with data of a Chinese colorectal cancer center.Records of 2080 nonmetastatic, advanced cancer patients undergoing colorectal cancer surgery from 1985 to 2011 were reviewed for T, N stage pathology and follow-up information. Using overall and disease-specific survival data, the 7th edition tumor, node, metastases staging system and the T-plus staging system were compared for stage homogeneity and discrimination and gradient monotonicity.For gradient monotonicity, the T-plus staging system was superior for both colon and rectal cancer. With Kaplan-Meier survival curves, the T-plus staging system discriminated among different stages, and the corresponding survival was inversely associated with the stage. However, for the 7th edition tumor, node, metastases staging system, stage IIIa had a better prognosis than stage II for rectal cancer and stage I for colon cancer. For homogeneity within the same stage and discrimination between different stages, the 2 staging systems were similar for colorectal cancer, but the T-plus system was clearly better for colon cancer.The T-plus staging system provides good gradient monotonicity. For future colorectal cancer staging systems, we propose replacement of lymph node status as the criterion to discriminate colorectal cancer stage II and stage III with greater weighting of the T stage. PMID- 26871808 TI - Association Between Cd Exposure and Risk of Prostate Cancer: A PRISMA-Compliant Systematic Review and Meta-Analysis. AB - Several observational studies on the association between Cd exposure and risk of prostate cancer have yielded inconsistent results. To address this issue, we conducted a meta-analysis to evaluate the correlation between Cd exposure and risk of prostate cancer.Relevant studies in PubMed and Embase databases were retrieved until October 2015. We compared the highest and lowest meta-analyses to quantitatively evaluate the relationship between Cd exposure and risk of prostate cancer. Summary estimates were obtained using a random-effects model.In the general population, high Cd exposure was not associated with increased prostate cancer (OR 1.21; 95% CI 0.91-1.64), whereas the combined standardized mortality ratio of the association between Cd exposure and risk of prostate cancer was 1.66 (95% CI 1.10-2.50) in populations exposed to occupational Cd. In addition, high D Cd intake (OR 1.07; 95% CI 0.96-1.20) and U-Cd concentration (OR 0.86; 95% CI 0.48-1.55) among the general population was not related to the increased risk of prostate cancer. In the dose analysis, the summary relative risk was 1.07 (95% CI 0.73-1.57) for each 0.5 MUg/g creatinine increase in U-Cd and 1.02 (95% CI 0.99 1.06) for each 10 MUg/day increase of dietary Cd intake. However, compared with nonoccupational exposure, high occupational Cd exposure may be associated with the increased risk of prostate cancer.This meta-analysis suggests high Cd exposure as a risk factor for prostate cancer in occupational rather than nonoccupational populations. However, these results should be carefully interpreted because of the significant heterogeneity among studies. Additional large-scale and high-quality prospective studies are needed to confirm the association between Cd exposure and risk of prostate cancer. PMID- 26871811 TI - Observational Study: Familial Relevance and Oncological Significance of Revised Bethesda Guidelines in Colorectal Patients That Have Undergone Curative Resection. AB - Amsterdam criteria for the hereditary nonpolyposis colorectal cancer (HNPCC) exclude most suspect cases of possible hereditary colorectal cancer (CRC). By contrast, revised Bethesda guidelines excessively broaden the disease spectrum. The aim of this study is to retrospectively evaluate the cliniciopathilogical characteristics of patients fulfilling the revised Bethesda guidelines and to review the efficacy and limitations of the revised guidelines.This retrospective study enrolled 3609 patients who underwent curative surgery for primary CRC. Patients were classified into the Bethesda group or the control group according to whether they fulfilled the revised Bethesda guidelines. Patients were further categorized when they fulfilled a minimum of 2 items of the revised guidelines. Individual items were analyzed for deficient mismatch repair (d-MMR).The median follow-up was 82.9 (interquartile range, 72-101) months. Patients in the Bethesda group were younger and had a higher rate of reduced mismatch repair (MMR) protein expression, microsatellite instability, and right colonic involvement (all P < 0.001) than the control group. As a predictor of d-MMR, the revised Bethesda guidelines showed a sensitivity of 63.0% and a specificity of 72.6%. Items 1 and 2, respectively, or the item pair 1 and 2, were independent predictors of d-MMR (all P < 0.001). Patients fulfilling the Bethesda guidelines showed clinicopathological features of HNPCC.The revised Bethesda guidelines appear to be a competent predictor of d-MMR. Specifically, items 1 and 2 are significant predictors of d-MMR and may be relevant to the application of the revised Bethesda guidelines. PMID- 26871812 TI - Platelet to Lymphocyte Percentage Ratio Is Associated With Brachial-Ankle Pulse Wave Velocity in Hemodialysis. AB - Increased arterial stiffness in patients receiving hemodialysis (HD) is highly prevalent and is associated with cardiovascular morbidity and mortality. In HD, inflammation is one of the major causes of increased arterial stiffness. Activation of platelets and decreased lymphocyte percentage (LYMPH%) may exhibit inflammation. The aim of this study is to examine the relationship between platelet to LYMPH% ratio and arterial stiffness in HD patients.A total of 220 patients receiving HD were enrolled in this study. The brachial-ankle pulse wave velocity (baPWV) was measured using an ankle-brachial index form device. Multivariate linear regression analysis was performed to investigate the relations of the platelet to LYMPH% ratio and baPWV. The value of the platelet to LYMPH% ratio was 59.2 +/- 33.3 (10 cells/L/%). After multivariate stepwise analysis, diabetes (beta: 163.973, P = 0.02), high systolic blood pressure (per 1 mm Hg, beta: 9.010, P < 0.001), high platelet to LYMPH% ratio (per 10 cells/L/%, beta: 3.334, P < 0.01), and low albumin (per 0.1 mg/dL, beta: -55.912, P < 0.001) were independently associated with an increased baPWV. Furthermore, high white blood cells (per 10 cells/L, beta: 3.941, P < 0.001), high neutrophil percentage (per 1%, beta: 1.144, P < 0.001), and high CRP (per 1 mg/L, beta: 9.161, P = 0.03) were independently associated with an increased platelet to LYMPH% ratio.An increased platelet to LYMPH% ratio is associated with an increased baPWV in HD patients. An easy and inexpensive laboratory measure of platelet to LYMPH% ratio may provide an important information regarding arterial stiffness in patients with HD. PMID- 26871813 TI - Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study. AB - Programmed cell death 4 (PDCD4) is a novel tumor suppressor, which is involved in the initiation and progression of cancers. However, the role of PDCD4 in hepatocellular carcinoma (HCC) has not been reported. The aim of this study was to investigate the molecular mechanism and clinical significance of PDCD4 inactivation in HCC.The mRNA levels of PDCD4 in HCC tissues and adjacent nontumor tissues were analyzed by quantitative real-time polymerase chain reaction (qRT PCR). Bisulfite sequencing PCR was performed to determine the methylation status of PDCD4 promoter. Furthermore, the mRNA expression level and the methylated level of PDCD4 were analyzed with the clinical and pathological characteristics.qRT-PCR analysis showed that PDCD4 mRNA levels in tumor tissues were significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of PDCD4 promoter was significantly higher in HCC tissues than that in adjacent nontumor tissues. PDCD4 mRNA levels and promoter methylation levels were both statistically correlated with metastasis and the degree of differentiation in HCC. In addition, the correlation between PDCD4 hypermethylation, mRNA levels, and overall survival (OS) was statistically significant.Our results indicated that PDCD4 may be a novel candidate of tumor suppressor gene in HCC, and that promoter hypermethylation is an important mechanism for its downregulation and is also a good predictor of OS for HCC. PMID- 26871814 TI - Adult Degenerative Scoliosis: Can Cobb Angle on a Supine Posteroanterior Radiograph Be Used to Predict the Cobb Angle in a Standing Position? AB - It is necessary to assess coronal Cobb angle in the diagnosis and treatment of patients with adult degenerative scoliosis (ADS). But as most ADS patients are elderly patients who are difficult or unable to stand upright without assistance, it is difficult to obtain standing posteroanterior X-ray radiographs. Whether it is possible to use Cobb angle obtained on a supine posteroanterior X-ray radiograph to predict Cobb angle in a standing position remains unanswered.To study the correlation between X-ray plain radiographic parameters obtained from the supine position and those obtained from the standing position in ADS patients.Medical records and radiological information were obtained from ADS patients prospectively. Posteroanterior X-ray views of the spine were taken in both standing and supine positions simultaneously in the same ADS patients to record information about the position of the apical and end vertebrae in the coronal position and measure Cobb angle and rotation degree of the apical vertebra. Correlation and linear regression were used to analyze the correlation between the Cobb angle and the rotation degree of the apical vertebra on the X ray plain radiographs obtained from the standing and supine positions.Of 94 ADS patients who met the inclusion criteria, 14 (15%) patients were male and 80 (85%) patients were female who ranged in age from 41 to 92 years with a mean of 67 years. The mean Cobb angle on the supine X-ray radiographs was 21 +/- 10 degrees versus 26 +/- 12 degrees on the standing X-ray radiographs, the difference being statistically significant (P < 0.01). The rotation angle of the apical vertebra in the supine and standing positions was 1.8 +/- 0.7 and 1.9 +/- 0.7, respectively, the difference being statistically significant (P < 0.05). Correlation analysis showed a strong correlation in Cobb angle between the supine and standing X-ray plain radiographs (r = 0.92, P < 0.01). The correlation coefficient of the rotation of the apical vertebra was rho = 0.81 (P < 0.01). The equation of predicting the standing Cobb angle from the supine position as shown by the linear regression analysis is as follows: standing Cobb angle = 1.15 * supine Cobb angle + 1.53 (R = 0.838). There was no significant difference between supine Cobb angle +5 degrees and standing Cobb angle (P = 0.413).The posteroanterior X-ray plain radiograph of the spine can provide information similar to that obtained from the standing coronary position in ADS patients, including the position of the apical and end vertebrae. There was a strong correlation between the Cobb angle and the degree of rotation of the apical vertebra on the X-ray radiographs obtained from the supine and standing positions, indicating that the supine Cobb angle can be used to predict the Cobb angle on the standing X-ray radiograph. The supine X-ray radiograph can replace the standing posteroanterior radiograph in terms of the coronal parameters. PMID- 26871815 TI - Cytomegalovirus Infection in Ireland: Seroprevalence, HLA Class I Alleles, and Implications. AB - Cytomegalovirus (CMV) infections occur worldwide and primary infection usually occurs in early childhood and is often asymptomatic whereas primary infection in adults may result in symptomatic illness. CMV establishes a chronic latent infection with intermittent periods of reactivation. Primary infection or reactivation associate with increased mortality and morbidity in those who are immunocompromised. Transplacental transmission may result in significant birth defects or long-term sensorineural hearing loss.We performed a study to determine the CMV seroprevalence and the association between HLA Class I alleles and frequency of CMV infection in Ireland. The presence of CMV IgG, a marker of previous CMV infection, was determined for a cohort of 1849 HLA typed solid organ transplant donors between 1990 and 2013. The presence of CMV IgG was correlated with HLA type.The CMV seroprevalence in solid organ transplant donors was 33.4% (range 22-48% per annum) over the time period 1990 to 2013. Multivariate logistic regression analysis showed that both age and HLA alleles were associated with CMV seropositivity. A significant and positive relationship between age and CMV seropositivity was observed (OR = 1.013, P < 0.001, CI [1.007, 1.019]). Chi square analysis revealed that the female gender was independently associated with CMV seropositivity (P < 0.01). Seroprevalence in women of reproductive age (20-39 years) was significantly higher than men of the same age (37% vs 26%, P < 0.01). The frequencies of HLA-A1, HLA-A2, and HLA-A3 in our cohort were 40.8%, 48.8%, and 25.9%, respectively. Logistic regression analysis showed that the presence of HLA-A1 but not HLA-A2 or HLA-A3 was independently associated with CMV seronegativity (P < 0.01). Interestingly, individuals who co-expressed HLA-A2 and HLA-A3 alleles were significantly more likely to be CMV seropositive (P < 0.02). The frequencies of HLA-B5, HLA-B7, and HLA-B8 in our cohort were 6.1%, 31.2%, and 30.8%, respectively. The presence of the most common inherited haplotype in the Irish population, HLA-A1, B8 was significantly associated with CMV seronegativity (OR = 1.278, P < 0.001, CI [1.049, 1.556]).CMV seroprevalence is lower in Ireland compared with other countries. The high frequency of HLA-A1 in the Irish population may, in part, have a role in the reduced susceptibility to CMV infection. PMID- 26871816 TI - Per-Oral Endoscopic Myotomy Versus Laparoscopic Heller Myotomy for Achalasia: A Meta-Analysis of Nonrandomized Comparative Studies. AB - We aimed to assess the short-term outcomes of per-oral endoscopic myotomy (POEM) compared with laparoscopic Heller myotomy (LHM) for achalasia through a meta analysis of nonrandomized comparative studies.We searched PubMed, Embase, Medline, Cochrane Library, and Google Scholar for studies that compared POEM and LHM for achalasia and were published between January 1, 2008 and December 31, 2014. The Methodological Index for Nonrandomized Studies (MINORS) was used to evaluate the quality of the studies. Random- and fixed-effects meta-analytical models were used, and between-study heterogeneity was assessed.Four nonrandomized comparative studies that included 317 patients (125 in the POEM group and 192 in the LHM group) met our research criteria and were assessed. There were no differences between the POEM and LHM groups in terms of sex, preoperative Eckhart score, length of myotomy, operation time, length of hospital stay, and complications. The patients in the POEM group were older than those in the LHM group (MD =2.81, 95% CI 0.27-5.35; P = 0.03) with high between-study homogeneity (chi = 1.96, df = 2, I = 0%; P = 0.38). The patients in the POEM group had a lower Eckardt score after surgery compared with those in the LHM group (MD = 0.30, 95% CI -0.42 to -0.18; P < 0.001) with high between-study homogeneity (chi = 0.00, df = 1, I = 0%; P = 1.00).The efficacy and safety of POEM appear to be comparable to those of LHM. Multicenter and randomized trials with larger sample size are needed to further compare the efficacy and safety of POEM and LHM for the treatment of achalasia. PMID- 26871817 TI - Influence of Renal Insufficiency on the Prescription of Evidence-Based Medicines in Patients With Coronary Artery Disease and Its Prognostic Significance: A Retrospective Cohort Study. AB - The purpose of this study was to discuss the present situation of discharge medications in coronary artery disease (CAD) patients with different levels of renal function and assess the potential impact of these medications on the prognosis of this patient population.A retrospective cohort study was conducted. From July 2008 to Jan 2012, consecutive patients with CAD confirmed by coronary angiography of West China Hospital were enrolled and were grouped into 3 estimated glomerular filtration rate (eGFR) categories: >=60, 30 to 60, and <30 mL/min/1.73 m. The endpoints were all-cause mortality and cardiac mortality.There are 3002 patients according to the inclusion criteria and follow-up requirement. The mean follow-up time was 29.1 +/- 12.5 months. CAD patients with worse renal function included more cardiovascular risk factors (advanced age, history of hypertension or diabetes, and diagnosis of acute myocardial infarction). The cumulative survival curves of the patients according to renal function showed that the eGFR <30 mL/min and 30 mL/min <= eGFR <60 mL/min groups had a significantly higher risk of all-cause death and cardiovascular death than the group with an eGFR >=60 mL/min. The prescription of evidence-based medicines (EBMs) at discharge (antiplatelet agents, beta-blockers, statins, and angiotensin converting enzyme inhibitors [ACEIs] or angiotensin-receptor blockers [ARBs]) was a factor in reducing the risk of all-cause death and cardiovascular death. However, EBMs prescribed at discharge revealed an obvious underuse in renal insufficiency (RI) patients. The results of Cox regression showed that irrespective of the eGFR level, greater use of EBMs resulted in a greater reduction in the risk of all-cause death and cardiovascular death.A higher percentage of patients with CAD and concomitant RI suffered from cardiovascular disease (CVD) risk factors, whereas a lower percentage of these patients used EBMs to prevent CVD events. Strict use of EBMs, including beta-blockers, statins, and ACEIs or ARBs, can lead to more clinical benefits, even for patients with CAD and concomitant RI. Thus, treatment of this patient population with EBMs should be stressed. PMID- 26871819 TI - Impact of Previous Stroke on Short-Term Myocardial Reinfarction in Patients With Acute ST Segment Elevation Myocardial Infarction: An Observational Multicenter Study. AB - Myocardial reinfarction is frequent after ST-elevation myocardial infarction (STEMI). The incidence of previous stroke in STEMI patients is also high. We aim to evaluate the risk factors for short-term myocardial reinfarction in STEMI patients in a multicenter study.STEMI patients with chest pain onset within 12 hours in 247 hospitals in China were enrolled. Seven and 30-day follow-ups from admission to hospitals were performed. The primary outcome of our study was myocardial reinfarction at 30 days after STEMI. The study population was stratified into 2 groups: STEMI patients with mayocardial reinfarction and without mayocardial reinfarction. Survival curve was constructed using Kaplan Meier survival methods with log-rank statistics. Multivariable Cox regression model was performed to determine the risk factors for myocardial reinfarction events in STEMI patients.A total of 6876 STEMI patients were enrolled. The proportion of STEMI patients with previous stroke was 9.4%. Rate of 30-day myocardial reinfarction was 2.0% among all STEMI patients. Rate of 30-day myocardial reinfarction was 4.2% in STEMI patients with previous stroke which was statistically higher than that in STEMI patients without previous stroke (P < 0.001). Multivariable Cox regression analysis showed that previous stroke (HR, 3.673; 95% CI, 1.180-11.43) and statin use (HR, 0.230; 95% CI, 0.080-0.664) were independent predictors for 30-day myocardial reinfarction.A large proportion of STEMI patients had previous stroke history. Short-term myocardial reinfarction after STEMI is not infrequent. STEMI patients with previous stroke confronted higher rates of short-term myocardial reinfarction and statin could decline the risk of short-term myocardial reinfarction. PMID- 26871818 TI - Warfarin Use and Risk of Stroke in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Meta-Analysis. AB - In spite of the substantial burden of atrial fibrillation and associated elevated ischemic stroke risk in patients undergoing hemodialysis, the role of warfarin in these high-risk patients remains uncertain. Our objective was to clarify the association between warfarin use and risk of stroke for patients with atrial fibrillation undergoing dialysis.PubMed and Embase from January 1966 to January 2015 were searched to identify relevant studies. Inclusion criteria were cohort studies, patients with atrial fibrillation undergoing hemodialysis, and reported quantitative estimates of the multivariate adjusted relative risk (RR) and 95% confidence interval (CI) for future stroke associated with warfarin use. We identified 8 studies, with a total of 9539 participants and 706 stroke events. Three studies reported total stroke as primary endpoint and other studies reported ischemic stroke as primary endpoint. Pooling the results showed that warfarin use was associated with higher risk of any stroke (RR 1.50, 95% CI: 1.13 1.99). By stroke type, warfarin was not significantly linked to risk of ischemic stroke (RR 1.01, 95% CI: 0.65-1.57, P = 0.97), but was related to greater hemorrhagic stroke risk (RR 2.30, 95% CI: 1.62-3.27). Warfarin heightened overall bleeding risk (RR 1.27, 95% CI: 1.03-1.56), but not death (RR 0.67, 95% CI: 0.37 1.21).Among patients with atrial fibrillation undergoing hemodialysis, use of warfarin is associated with a higher risk of hemorrhagic stroke, but did not increase overall mortality. PMID- 26871820 TI - Clinical Immunophenotype at Disease Onset in Previously Healthy Patients With Cryptococcal Meningitis. AB - Cryptococcal meningitis (CM) is a global disease with significant morbidity and mortality. Although low peripheral blood cluster of differentiation 4 (CD4) cell counts are found to be related to a high burden of cryptococcus in HIV-infected patients, little is known about possible immune defects in previously healthy patients (PHPs). We performed a retrospective study of 41 CM patients treated from January 2005 to December 2014 who did not have HIV-infection. There were 33 PHPs and 8 not previously healthy patients (non-PHPs). We analyzed clinical test data pertaining to peripheral blood T cells, antibodies, inflammation markers, and cerebral spinal fluid (CSF) completed during the disease onset phase and 5 years following diagnosis. PHPs had significantly higher counts of cluster of differentiation 3 (CD3), cluster of differentiation 4 (CD4), and cluster of differentiation 45 (CD45) cells, and lower percentages of CD8 cells than non-PHPs (P < 0.05). Measurements of inflammatory markers and immunoglobulin in blood were comparable except for lower immunoglobulin A (IgA) levels in non-PHPs (P = 0.0410). Examination of CSF revealed lower white blood cell (WBC) counts in non PHPs. Five-year mortality in PHPs was higher than in non-PHPs (22.0% vs 12.5%) but this was not statistically significant (P > 0.05). Multivariate analysis revealed that higher immunoglobulin G (IgG) levels in serum during disease onset may be an independent predictor of mortality (P = 0.015). In conclusion, PHPs demonstrate an immunophenotype that is distinct from that of non-PHPs, leading to an improved understanding of the immunology of cryptococcal meningitis. PMID- 26871821 TI - The Relation Between Sacral Angle and Vertical Angle of Sacral Curvature and Lumbar Disc Degeneration: A Case-Control Study. AB - The purpose of this study is to determine the reliability and validity of a goniometric measurement of the vertical angle of the sacrum and sacral angle (SA), and their relationships to lumbar degeneration.A herniated lumbar disc is one of the most frequent medical issues. Investigators in a number of studies have reported associated risk factors for prevalent disc degeneration. Atypical lumbosacral angles and curvature are thought to contribute to the degradation of the spine by many researchers. This study analyzed 360 patients referred to our clinic from 2013 to 2015 due to low back pain. A cross-sectional case-control study was designed in order to compare the sagittal alignment of the lumbosacral area in 3 groups of patients suffering from LBP. A total 120 patients were in a control group with a normal lumbar magnetic resonance imaging (MRI), 120 patients had lumbar disk herniation (LDH), and 120 patients had spinal stenosis. From the sagittal plan of lumbar MRI, SA and vertical angle of sacral curvature (VASC) were determined and then analyzed.The means of VASC in these groups were: 38.98 (SD: 6.36 +/- 0.58), 40.89 (SD: 7.69 +/- 0.69), and 40.54 (SD: 7.13 +/- 0.92), respectively (P = 0.089). Moreover, studies of SA in 3 groups showed that the means of SA were: 39.30 (SD: 6.69 +/- 0.63), 40.52 (SD: 7.47 +/- 0.65), and 35.63 (SD: 6.07 +/- 0.79), respectively. Relation between SA and spinal stenosis was just statistically significant (P <= 0.05).One significant limitation of our study is the lack of standing MRI for increased accuracy of measurement. However, we were reluctant to give patients needless exposure to radiation from conventional X-ray, and instead used MRI scans. We did not find any significant correlation between the VASC and LDH in lumbar MRI. Also, SA is not an independent risk factor for LDH in men and women. We suggested that there are several biomechanical factors involved in LDH. PMID- 26871822 TI - Transient Monoplegia as a Result of Unilateral Femoral Artery Ischemia Detected by Multimodal Intraoperative Neuromonitoring in Posterior Scoliosis Surgery: A Case Report. AB - This is to report a case of 16-year-old girl with transient right lower limb monoplegia as a result of femoral artery ischemia detected by multimodal intraoperative spinal cord neuromonitoring (MISNM) during posterior correction surgery of adolescent idiopathic scoliosis.A patient with a marfanoid body habitus and LENKE IA type scoliosis with the right thoracic curve of 48 degrees of Cobb angle was admitted for posterior spinal fusion from Th6 to L2. After selective pedicle screws instrumentation and corrective maneuvers motor evoked potentials (MEP) began to decrease with no concomitant changes in somato-sensory evoked potentials recordings.The instrumentation was released first partially than completely with rod removal but the patient demonstrated constantly increasing serious neurological motor deficit of the whole right lower limb. Every technical cause of the MEP changes was eliminated and during the wake-up test the right foot was found to be pale and cold with no popliteal and dorsalis pedis pulses palpable. The patient was repositioned and the pelvic pad was placed more cranially. Instantly, the pulse and color returned to the patient's foot. Following MEP recordings showed gradual return of motor function up to the baseline at the end of the surgery, whereas somato-sensory evoked potentials were within normal range through the whole procedure.This case emphasizes the importance of the proper pelvic pad positioning during the complex spine surgeries performed in prone position of the patient. A few cases of neurological complications have been described which were the result of vascular occlusion after prolonged pressure in the inguinal area during posterior scoliosis surgery when the patient was in prone position. If incorrectly interpreted, they would have a significant impact on the course of scoliosis surgery. PMID- 26871824 TI - Clinical Features and Outcomes of Patients With Genotype 3 Hepatitis C Virus Infection in Korea: A Retrospective Observational Study. AB - Hepatitis C virus (HCV) genotype 3 infection is very rare in high-income Asia Pacific. The aim of our retrospective observational study was to evaluate the incidence, clinical features, and treatment outcomes of patients with a genotype 3 HCV infection in the Gyeongnam Province of Korea. Ninety-eight consecutive patients diagnosed with a genotype 3 HCV infection at Gyeongsang National University Hospital, between January 2005 and December 2014, were enrolled into the study. Relevant characteristics of the study group included: 80.6% men, mean age of 41.8 years, and including 69 patients with chronic hepatitis, 25 with liver cirrhosis, and 4 with hepatocellular carcinoma (HCC). Risk factors for HCV infection, sustained virologic response rate, development of HCC, and mortality in patients with genotype 3 were retrospectively analyzed.Among all patients diagnosed with a HCV infection during the study period, the prevalence of genotype 3 was 7.3%. The incidence of genotype 3 was higher in young patients with a risk factor of IVDU (54.0%) and tattooing (62.3%). Among 45 treatment naive genotype 3 patients, sustained virologic response was achieved with a combination of pegylated-interferon alpha and ribavirin in 75.6%. The cumulative 5-year incidence of HCC was 13.6%, and 8.9% for overall mortality. Liver cirrhosis at enrollment was an independent risk factor for HCC development.This is the first study to elucidate the clinical features and outcomes among the patients with HCV genotype 3 infection in Korea. Further prospective studies are needed to investigate transmission routes and outcomes for HCV genotype 3 infections. PMID- 26871823 TI - Small-Cell Lung Cancer Transformation in Patients With Pulmonary Adenocarcinoma: A Case Report and Review of Literature. AB - Despite the demonstrated benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) based therapies, EGFR mutant lung adenocarcinoma will eventually acquire drug resistance. Transformation to small-cell lung cancer (SCLC) is considered to be a rare resistance mechanism of EGFR-TKI therapy.We describe a case of a 46-year-old man presenting with refractory cough. Percutaneous transthoracic biopsy was performed and confirmed an EGFR exon 21 L858R lung adenocarcinoma. However, the patient relapsed after successful treatment with gefitinib for 1 year, at which point rebiopsy identified an SCLC and chemotherapy composed of platinum and pemetrexed was started. However, despite the brief success of chemotherapy, our patient died of aggressive cancer progression and complications of chemotherapy.Our case highlights the importance of rebiopsy when managing drug resistance and presents a possible origin of the transformed cells. We also summarize the clinical characteristics of cases involving transformed SCLC from previous studies and discuss whether it could be a new subtype of SCLC. PMID- 26871825 TI - The Epidemiological Investigation on the Risk Factors of Hepatocellular Carcinoma: A Case-Control Study in Southeast China. AB - Incidence of hepatocellular carcinoma (HCC) ranked the fifth in male and ninth in the female counterparts, and 50% of incidence HCC cases were occurred in China with high hepatitis B virus (HBV) prevalence. HCC has seriously compromised the health status of general population in China. A case-control study of 314 HCC cases and 346 controls was conducted in Xiamen, which is an epidemic area in China for both hepatitis B infection and HCC. Face-to-face interview was conducted to gather information on demographic characteristics as well as exposure of environmental factors. Commercial enzyme-linked immunosorbent assay kits were used to determine the status of serological markers of HBV infection. Odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders.As expected, HBV and alcohol intake still are the major risk factors of HCC. Liver disease history and passive smoking are also associated with elevated HCC risk. Indoor air pollution and pesticide exposure have newly identified as risk factors of HCC. Fruit and tea intake can significantly lower the HCC risk.The application of HBV vaccine and reduction on alcohol intake should be further promoted in high risk population. Fruit and tea can be served as chemoprevention in daily life due to their high accessibility. PMID- 26871826 TI - Using a Distant Abdominal Skin Flap to Treat Digital Constriction Bands: A Case Report for Vohwinkel Syndrome. AB - In this study, a Vohwinkel syndrome case is presented where in 5th digit constriction bands in the right hand were reconstructed using a distant abdominal skin flap. Vohwinkel syndrome, or keratoderma hereditarium mutilans, is a rare, autosomal dominant genetic skin condition that causes palmoplantar hyperkeratosis and constricts finger and/or toe bands. In a typical manifestation, the finger and toe constriction bands lead to progressive strangulation and autoamputation, which requires immediate clinical treatment. Topical keratolytics and systemic retinoids have been used to treat hyperkeratosis but without consistent results. Only 1 effective approach for autoamputation has been accepted, reconstructive surgery.Applying a distant abdominal skin flap produced satisfying postoperative effects at the 18-month follow-up. PMID- 26871827 TI - Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia: A Nationwide Population Based Cohort Study. AB - Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to beta-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics.This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups.After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77-0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92-1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30-1.62) between the 2 groups.The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID- 26871828 TI - Developing and Evaluating Medical Humanities Problem-Based Learning Classes Facilitated by the Teaching Assistants Majored in the Liberal Arts: A Longitudinal Crossover Study. AB - Although medical humanities courses taught by teachers from nonmedical backgrounds are not unusual now, few studies have compared the outcome of medical humanities courses facilitated by physicians to that by teaching assistants majored in the liberal arts. The objectives of this study were to (1) analyze the satisfaction of medical students with medical humanities problem-based learning (PBL) classes facilitated by nonmedical teaching assistants (TAF) majored in the liberal arts, and those facilitated by the attending physicians (APF) and (2) examine the satisfaction of medical students with clinical medicine-related and clinical medicine-unrelated medical humanities PBL classes.A total of 123 medical students, randomly assigned to 16 groups, participated in this study. There were 16 classes in the course: 8 of them were TAF classes; and the others were APF classes. Each week, each group rotated from 1 subject of the 16 subjects of PBL to another subject. All of the 16 groups went through all the 16 subjects in the 2013 spring semester. We examined the medical students' satisfaction with each class, based on a rating score collected after each class was completed, using a scale from 0 (the lowest satisfaction) to 100 (the highest satisfaction). We also conducted multivariate linear regression analysis to examine the association between the independent variables and the students' satisfaction.Medical students were more satisfied with the TAF (91.35 +/- 7.75) medical humanities PBL classes than APF (90.40 +/- 8.42) medical humanities PBL classes (P = 0.01). Moreover, medical students were more satisfied with the clinical medicine-unrelated topics (92.00 +/- 7.10) than the clinical medicine-related topics (90.36 +/- 7.99) in the medical humanities PBL course (P = 0.01).This medical humanities PBL course, including nonmedical subjects and topics, and nonmedical teaching assistants from the liberal arts as class facilitators, was satisfactory. This pedagogical approach of student-centered, nonmedical topics, nonmedical facilitators, and small groups, which is associated with a deep approach to learning medical humanities, should be highly encouraged. PMID- 26871829 TI - Successful Treatment of Lung Calciphylaxis With Sodium Thiosulfate in a Patient With Sickle Cell Disease: A Case Report. AB - Calciphylaxis is a small vessel vasculopathy, characterized by medial wall calcification that develops in a few patients with chronic renal failure. The prognosis of skin calciphylaxis has improved considerably since the introduction of sodium thiosulfate (STS), but it remains unclear whether this therapy is effective against organ lesions related to calciphylaxis. Pulmonary calciphylaxis is a usually fatal medical condition that may occur in association with skin involvement in patients with end-stage renal disease.We report here the case of a 49-year-old woman homozygous sickle cell disease patient on chronic hemodialysis with biopsy-proven systemic calciphylaxis involving the lungs and skin. On admission, ulcerative skin lesions on the lower limbs and bilateral pulmonary infiltrates on chest computerized tomography scan were the main clinical and radiological findings. Skin and bronchial biopsies demonstrated calciphylaxis lesions. The intravenous administration of STS in association with cinacalcet for 8 consecutive months led to a clear improvement in skin lesions and thoracic lesions on chest computerized tomography scan.This case suggests for the first time that organ lesions related to calciphylaxis, and particularly lung injury, are potentially reversible. This improvement probably resulted from the combination of 3 interventions (more frequent dialysis, cinacalcet, and STS), rather than the administration of STS alone. PMID- 26871830 TI - Validation of Serological Antibody Profiles Against Human Papillomavirus Type 16 Antigens as Markers for Early Detection of Cervical Cancer. AB - Cervical cancer (CC) is the second most frequent neoplasia among women worldwide. Cancer prevention programs around the world have used the Papanicolaou (Pap) smear as the primary diagnostic test to reduce the burden of CC. Nevertheless, such programs have not been effective in developing countries, thus leading to research on alternative tests for CC screening. During the virus life cycle and in the process toward malignancy, different human papillomavirus (HPV) proteins are expressed, and they induce a host humoral immune response that can be used as a potential marker for different stages of the disease. We present a new Slot blot assay to detect serum antibodies against HPV16 E4, E7, and VLPs-L1 antigens. The system was validated with sera from a female population (n = 485) aged 18 to 64 years referred to the dysplasia clinic at the General Hospital in Cuautla, Morelos, Mexico. To evaluate the clinical performance of the serological markers, the sensitivity, specificity, positive, and negative predictive values and receiver-operating characteristic curves (for antibodies alone or in combination) were calculated in groups of lesions of increasing severity. The results showed high prevalence of anti-E4 (73%) and anti-E7 (80%) antibodies in the CC group. Seropositivity to 1, 2, or 3 antigens showed associations of increasing magnitude with CC (odds ratio [OR] = 12.6, 19.9, and 58.5, respectively). The highest association with CC was observed when the analysis was restricted to only anti E4+E7 antibodies (OR = 187.7). The best clinical performance to discriminate CC from cervical intraepithelial neoplasia 2 to 3 was the one for the combination of anti-E4 and/or anti-E7 antibodies, which displayed high sensitivity (93.3%) and moderate specificity (64.1%), followed by anti-E4 and anti-E7 antibodies (73.3% and 80%; 89.6% and 66%, respectively). In addition, the sensitivity of anti-E4 and/or anti-E7 antibodies is high at any time of sexual activity (TSA), which suggests they can be biomarkers for the early detection of CC. The sensitivity of anti-E4 antibodies was low (<10%) when the TSA was <10 years, and it increased up to 100% in relation to the TSA, suggesting that anti-E4 antibodies can be useful as HPV exposure markers at early stages of the disease. PMID- 26871831 TI - Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes: A Diagnostic Accuracy and Observational Outcome Study. AB - In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far.This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality.One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367-557) in patients with AAS and 383 U/L (IQR 331-460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37-51) and the specificity was 73% (95% CI 69-76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH >= 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH >= 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11-4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH >= 450 U/L in elderly, hemodynamically stable and in nonsurgically treated patients.Plasma LDH constitutes a biomarker of poor outcome in patients with AAS. LDH is a rapid and universally available assay that could be used to improve risk stratification and to individualize treatment in patient groups where options are controversial. PMID- 26871833 TI - Hemodynamic Effects of Nasal Intermittent Positive Pressure Ventilation in Preterm Infants. AB - Nasal intermittent positive pressure ventilation (NIPPV) and nasal continuous positive airway pressure (NCPAP) have proven to be effective modes of noninvasive respiratory support in preterm infants. Although they are increasingly used in neonatal intensive care, their hemodynamic consequences have not been fully evaluated. The aim of this study was to investigate the hemodynamic changes between NIPPV and NCPAP in preterm infants.This prospective observational study enrolled clinically stable preterm infants requiring respiratory support received NCPAP and nonsynchronized NIPPV at 40/minute for 30 minutes each, in random order. Cardiac function and cerebral hemodynamics were assessed by ultrasonography after each study period. The patients continued the study ventilation during measurements.Twenty infants with a mean gestational age of 27 weeks (range, 25-32 weeks) and birth weight of 974 g were examined at a median postnatal age of 20 days (range, 9-28 days). There were no significant differences between the NCPAP and NIPPV groups in right (302 vs 292 mL/kg/min, respectively) and left ventricular output (310 vs 319 mL/kg/min, respectively), superior vena cava flow (103 vs 111 mL/kg/min, respectively), or anterior cerebral artery flow velocity.NIPPV did not have a significant effect on the hemodynamics of stable preterm infants. Future studies assessing the effect of NIPPV on circulation should focus on less stable and very preterm infants. PMID- 26871832 TI - Multinodular Goiter Spontaneous Hemorrhage in ESRD Patients Result in Acute Respiratory Failure: A Case Report. AB - Euthyroid multinodular goiters may lead to acute respiratory failure caused by airway obstruction or laryngotracheal compression. Here, we present a case admitted to the nephrologist with multinodular goiter spontaneous hemorrhage along with respiratory failure and end-stage renal disease (ESRD), which required urgent surgical intervention.We report the case of a 63-year-old woman with ESRD who presented with a rapidly enlarging nodular goiter resulting in acute respiratory failure. Endotracheal intubation and emergency partial thyroidectomy were performed, revealing multinodular goiter spontaneous hemorrhage by postoperative histopathology. Several cases of benign goiters necessitating endotracheal intubation have been reported. Goiters are among the rare diagnoses in patients consulting at our institution's Nephrology.This case illustrates that ESRD patients with benign goiter may lead to acute respiratory failure due to airway obstruction or laryngotracheal compression. It was found in agreement with previous reports. This case highlights that ESRD patient at risk of this life threatening complication such as multinodular goiter hemorrhage should be managed with elective thyroidectomy to reduce morbidity and mortality. PMID- 26871834 TI - The Efficacy of Taxanes- and Oxaliplatin-Based Chemotherapy in the Treatment of Gastric Cancer After D2 Gastrectomy for Different Lauren Types. AB - To investigate the efficacy of Taxanes- and Oxaliplatin-based chemotherapies (TC and OC) in the treatment of gastric cancer patients after D2 gastrectomy with different Lauren types. In this study, 299 patients of gastric adenocarcinoma with D2 lymph node dissection were reviewed between 2007 and 2014. Chemotherapies were classified as Oxaliplatin-based and Taxanes-based regimen. Treatment outcomes were analyzed according to different Lauren types, such as the intestinal type, diffuse type, and mixed type groups, respectively. The disease free survival (DFS) and overall survival (OS) were estimated using the Kaplan Meier method. The log-rank test was used for univariate analysis, and Cox regression was used for multivariate analysis. In diffuse type gastric cancer, the Oxaliplatin-based arm had a longer median DFS and OS compared with Taxanes based arm (DFS: 47.0 vs 28.6 months, P = 0.04; OS: 51.9 vs 34.5 months, P = 0.048). The chemotherapy regimen was an independent prognostic factor for DFS and OS of diffuse type gastric cancer patients by multivariate analysis (P = 0.01). In the intestinal type, although the DFS and OS of intestinal type patients in TC group were higher than those in OC group (DFS: 53.4 vs 42.4 months; OS: 69.7 vs 57.8 months), there was no statistical significance observed (both P > 0.05). For the mixed type, the 2 different chemotherapy regimens achieved similar median DFS and OS. In a conclusion, the patients of diffuse type were more sensitive to OC, and the intestinal type patients may be benefit from TC. Therefore, it will be of benefit for gastric patients by introducing Lauren classification clinically and to help the choice of chemotherapy regimen for gastric patients after D2 gastrectomy. PMID- 26871835 TI - Rosiglitazone Use and the Risk of Bladder Cancer in Patients With Type 2 Diabetes. AB - Patients with diabetes have a higher incidence of bladder cancer; however, the association between thiazolidinedione use and bladder cancer risk has been controversial. We aimed to investigate whether pioglitazone or rosiglitazone use is associated with bladder cancer risk in patients with type 2 diabetes mellitus.This nationwide nested case-control study used data set obtained from the Korean National Health Insurance Service National Sample Cohort 2002 to 2013. Among the 47,738 patients with incident diabetes, 85 cases of newly diagnosed bladder cancer and 850 controls (1:10 matched by age, sex, index year, and diabetes diagnosis year) were recruited. Type 2 diabetes mellitus and bladder cancer were diagnosed using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision code.More cases of bladder cancer were diagnosed in men (81.2%), and the stratified age peaked at 70 to 79 years old. Exclusive rosiglitazone use raised the incidence of bladder cancer (odds ratio [OR] = 3.07, 95% confidence interval [CI ] = 1.48-6.37). The risk of bladder cancer started to increase after less than 3 months use (OR = 3.30, 95% CI = 1.02-10.70) and peaked at 3 to 12 months of rosiglitazone use (OR = 4.48, 95% CI = 1.51-13.31). Patients were first exposed to exclusive rosiglitazone within 1 year (OR = 11.74, 95% CI = 2.46-56.12) and those who had consistently used it for 1 year (OR = 4.48 95% CI = 1.51-13.31), had higher risks of bladder cancer compared with nonthiazolidinedione users. Neither pioglitazone use nor exclusive pioglitazone use were associated with an increased incidence of bladder cancer.Rosiglitazone use is associated with an increased risk of incident bladder cancer independent of age and sex in patients with type 2 diabetes mellitus. The highest odds of bladder cancer in rosiglitazone users was seen in those with <1 year of exposure. PMID- 26871836 TI - GDP (Gemcitabine, Dexamethasone, and Cisplatin) Is Highly Effective and Well Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type. AB - This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2 8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL. PMID- 26871837 TI - Discharge Against Medical Advice From the Emergency Department: Results From a Tertiary Care Hospital in Beirut, Lebanon. AB - Patients who leave the emergency department against medical advice are at high risk for complications. Against medical advice (AMA) discharges are also considered high-risk events potentially leading to malpractice litigation.Our aim was to characterize patients who leave AMA in a payment prior to service emergency department (ED) model and to identify predictors for return visits to ED after leaving AMA.We conducted a retrospective review study of charts of ED patients who were discharged AMA between January 1, 2012 and January 1, 2013 at a tertiary care center in Beirut Lebanon. We carried out a descriptive analysis and a bivariate analysis comparing AMA patients without and with return visit within 72 hours. This was followed by a Logistic regression to identify predictors of return visits after leaving AMA.A total of 1213 ED patients were discharged AMA during the study period. Mean age was 46.9 years (+/-20.9). There were 654 men (53.9%), 737 married (60.8%). The majority (1059 patients (87.3%)) had an emergency severity index of 3 or less (1 or 2). ED average length of stay was 3.8 hours (+/-6.8). Self payers accounted for 53.9%. Reasons for leaving AMA were: no reason mentioned (44.1%), incomplete workup (30.5%), refusing admission (12.4%), financial reasons (7.9%), long wait times (2.9%), and others (2.2%). Discharge diagnoses were mainly cardiac (23.4%), gastrointestinal (16.4%), infectious (10.1%), and trauma (9.8%).One hundred nineteen returned to ED within 72 hours (9.8%). Predictors of returning to ED after leaving AMA were: older age (OR 1.02 95% CI (1.01-1.03)), private insurance status (OR 4.64 95% (CI 2.89-7.47) within network insurance status (OR 7.20 95% CI (3.86-13.44), longer ED length of stay during the first visit (OR 1.03 95% CI (1.01-1.05).In our setting, the rate of return visit to ED after leaving AMA was 9.8%. Reasons for leaving AMA, high-risk discharge diagnoses and predictors of return visit were identified. Financial status was a strong predictor of return to ED after leaving AMA. PMID- 26871838 TI - Radiotherapy Combined With Androgen Deprivation for Bone Oligometastases After Primary Curative Radiotherapy for Prostate Cancer: A Retrospective Study. AB - To evaluate the effects and toxicity of radiotherapy (RT) combined with androgen deprivation (AD) for bone oligometastases after primary curative RT for prostate cancer (PCa).We retrospectively analyzed 30 consecutively treated PCa patients with bone oligometastases from April 2005 to July 2014. All patients underwent RT combined with AD for oligometastatic bones after curative RT for PCa. Measured outcomes included overall survival (OS) rate, local control (LC), progression free survival (PFS), pain relief, and toxicities. Statistical analysis was performed with SPSS17.0.The median follow-up was 32.5 months (range, 0.6-50.3). The 3-year PFS and OS rates were 22.8% (95% CI, 13.4-37.5%) and 69% (95% CI, 51.7 81.1%), respectively. The number of bone oligometastases and RT schedule were found to be significantly associated with OS on univariate analysis (P < 0.05, respectively). The 3-year OS for patients with 1 and >1 metastases was 78.8% versus 42.2%, respectively (P = 0.037). The long-course RT was associated with better 3-year OS compared with short-course (76.4% vs 44.1%, P = 0.03). A total of 15 (83.3%, 15/18) patients achieved pain relief. No grade 3 toxicity was observed.Long-course RT combined with ADT was effective and well-tolerated in PCa patients with bone oligometastases after curative RT for PCa. Further randomized controlled trials are needed to corroborate the findings. PMID- 26871839 TI - Moxibustion is an Alternative in Treating Knee Osteoarthritis: The Evidence From Systematic Review and Meta-Analysis. AB - Knee osteoarthritis (KOA) is a common disorder in elderly. There is no known cure for KOA, and thus therapeutic strategies of alleviating symptoms are increasingly emphasized. Moxibustion has been widely used to treat KOA; however, results are inconclusive. The aim of our study is to critically reassess the effects of moxibustion on KOA.We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese Biomedical Literature database (CBM) through 25 November 2015. Two independent reviewers selected studies and abstracted information, as well as assessed the risk of bias using Cochrane risk of bias tool. The random-effects meta-analyses were performed based on abstracted data.We initially captured 163 citations and added 4 records through checking review. After critical appraisal, 13 RCTs were included. Meta-analyses indicated that moxibustion is not statistically different from oral drug in improving the response rate (MD = 1.09; 95% CI = 1.00, 1.20; P = 0.05), alleviating pain and improving physical function. Our meta-analysis also found that moxibustion is superior to usual care and sham moxibustion in reducing WOMAC score (MD = 7.56; 95% CI = 4.11, 11.00; P = 0.00), pain and function, as well as increasing QoL. Moreover, most AEs caused by moxibustion can heal without medical care.We concluded that moxibustion treatment is equal to the oral drugs and intra articular injections and may be an alternative in treating patients with KOA. PMID- 26871840 TI - Associations Between the Periodontal Disease in Women Before Menopause and Menstrual Cycle Irregularity: The 2010-2012 Korea National Health and Nutrition Examination Survey. AB - The association between menstrual cycle irregularities and system disease has been evaluated in previous studies. However, the association between periodontal disease and menstrual cycle irregularity has not been fully investigated. The study aimed to evaluate the relationship between periodontal disease and tooth loss in women before menopause and menstrual cycle irregularity using nationally representative data.This study performed a cross-sectional analysis and used hierarchical multivariable logistic regression analysis models. Data from Korean National Health and Nutrition Examination Survey (KNHANES) between 2010 and 2012 were analyzed. The analysis in this study was confined to a total of 1553 respondents over 19 years old who had not gone through menopause and had no missing values for the reproductive factors and outcome variables. A community periodontal index was greater than or equal to code 3 was used to define periodontal treatment needs.The risk of periodontal treatment needs tended to increase in the presence of menstrual cycle irregularity after adjustment for potential confounders (P for trend in the odds ratios = .0481 in model 1; 0.0613 in model 2; 0.0369 in model 3; 0.0456 in model 4). The number of natural teeth of 28 did not reach statistically significant differences (P for trend in the odds ratios = 0.2204 in model 1; 0.2373 in model 2; 0.2814 in model 3; 0.2609 in model 4).Menstrual cycle irregularity was positively associated with the risk of periodontal treatment needs in Korean women before menopause. However, there was no significant association between tooth loss and menstrual cycle irregularity. Menstrual cycle irregularity may be considered to be a potential risk indicator for periodontal treatment needs in Korean women before menopause. PMID- 26871841 TI - Distinctive Patterns of Initially Presenting Metastases and Clinical Outcomes According to the Histological Subtypes in Stage IV Non-Small Cell Lung Cancer. AB - This study was designed to compare the primary patterns of metastases and clinical outcomes between adenocarcinoma (Adenoca) and squamous cell carcinoma (SQ) in initially diagnosed stage IV non-small cell lung cancer (NSCLC).Between June 2007 and June 2013, a total of 427 eligible patients were analyzed. These patients were histologically confirmed as Adenoca or SQ and underwent systemic imaging studies, including 18F-fluorodeoxyglucose positron emission tomography/computed tomography and brain imaging. Synchronous metastatic sites were categorized into 7 areas, and whole-body metastatic scores were calculated from 1 to 7 by summation of each involved region. We compared the patient, tumor, and metastatic characteristics according to the histological subtypes, and examined clinical outcomes.The enrolled study cohort comprised 81% (n = 346) Adenoca patients and 19% (n = 81) SQ patients. The median age of the study population was 65 years (range, 30-94 years), and 263 (61.6%) patients were male. The most common metastatic sites were thoracic lymph nodes (LNs) (84.3%), followed by lung to lung/lymphangitic spread (59%) and bone (54.8%). The distribution of patient characteristics revealed that age >=65 years (69.1% vs 50.6%; P = 0.003) and male sex (84% vs 56.4%; P < 0.001) were more frequently found in SQ patients. Regarding metastatic features, bone metastasis (60.4% vs 30.9%; P < 0.001), lung to lung/lymphangitic metastasis (63% vs 42%; P = 0.001), and brain metastasis (35% vs 16%; P = 0.001) were significantly and more frequently found in Adenoca patients. Patients with high metastatic scores (score 3-6) were more frequently found to have Adenoca (91.6% vs 73.4%; P < 0.001). In multivariate prognostic evaluation, sex (P = 0.001), age (P < 0.001), histology (P < 0.001), LN status (P = 0.032), pleural/pericardial metastasis (P = 0.003), abdomen/pelvis metastasis (P < 0.001), axilla/neck metastasis (P = 0.006), and treatment factors (P < 0.001) remained independent prognostic factors affecting overall survival.We observed distinctive patterns of primary metastases and clinical outcomes according to the histological subtypes in stage IV NSCLC. Future studies need to disclose the underlying mechanism of these unique metastatic features and tumor biologies. PMID- 26871842 TI - Cervical Intradural Disc Herniation Causing Progressive Quadriparesis After Spinal Manipulation Therapy: A Case Report and Literature Review. AB - Cervical intradural disc herniation (IDH) is an extremely rare condition, comprising only 0.27% of all disc herniations. Three percent of IDHs occur in the cervical, 5% in the thoracic, and over 92% in the lumbar spinal canal. There have been a total of 31 cervical IDHs reported in the literature. The pathogenesis and imaging characteristics of IDH are not fully understood. A preoperative diagnosis is key to facilitating prompt intradural exploration in patients with ambivalent findings, as well as in preventing reoperation. The purpose of reporting our case is to remind clinicians to consider the possibility of cervical IDH during spinal manipulation therapy in patient with chronic neck pain.The patient signed informed consent for publication of this case report and any accompanying image. The ethical approval of this study was waived by the ethics committee of Chonbuk National University Hospital, because this study was case report and the number of patients was <3.A 32-year-old man was transferred our emergency department with progressive quadriparesis. He had no history of trauma, but had received physical therapy with spinal manipulation for chronic neck pain over the course of a month. The day prior, he had noticed neck pain and tingling in the bilateral upper and lower extremities during the manipulation procedure. The following day, he presented with bilateral weakness of all 4 extremities, which rendered him unable to walk. Neurological examination demonstrated a positive Hoffmann sign and ankle clonus bilaterally, hypoesthesia below the C5 dermatome, 3/5 strength in the bilateral upper extremities, and 2/5 strength in the lower extremities. This motor weakness was progressive, and he further complained of voiding difficulty.Urgent magnetic resonance imaging (MRI) of the cervical spine revealed large, central disc herniations at C4-C5 and C5-C6 that caused severe spinal cord compression and surrounding edema. We performed C4-C5-C6 anterior cervical discectomy and fusion.The patient's limb weakness improved rapidly within 1 day postoperatively, and he was discharged 4 weeks later. At his 12-month follow-up, the patient had recovered nearly full muscle power.We presented an extremely rare case of cervical IDH causing progressive quadriparesis after excessive spinal manipulation therapy. The presence of a "halo" and "Y-sign" were useful MRI markers for cervical IDH in this case. PMID- 26871843 TI - Risk of Psychiatric Disorders Following Symptomatic Menopausal Transition: A Nationwide Population-Based Retrospective Cohort Study. AB - Menopausal transition is highly symptomatic in at least 20% of women. A higher prevalence of psychiatric symptoms, including depression, anxiety, and sleep disturbance, has been shown in women with symptomatic menopausal transition. However, a clear correlation between symptomatic menopausal transition and psychiatric disorders has not been established.We explored the association between symptomatic menopausal transition and subsequent newly diagnosed psychiatric disorders, including schizophrenia as well as bipolar, depressive, anxiety, and sleep disorders.We investigated women who were diagnosed with symptomatic menopausal transition by an obstetrician-gynecologist according to the data in the Taiwan National Health Insurance Research Database. A comparison cohort comprised age-matched women without symptomatic menopausal transition. The incidence rate and the hazard ratios of subsequent newly diagnosed psychiatric disorders were evaluated in both cohorts, based on the diagnoses of psychiatrists.The symptomatic menopausal transition and control cohorts each consisted of 19,028 women. The incidences of bipolar disorders (hazard ratio [HR] = 1.69, 95% confidence interval [CI] = 1.01-2.80), depressive disorders (HR = 2.17, 95% CI = 1.93-2.45), anxiety disorders (HR = 2.11, 95% CI = 1.84-2.41), and sleep disorders (HR = 2.01, 95% CI = 1.73-2.34) were higher among the symptomatic menopausal transition women than in the comparison cohort. After stratifying for follow-up duration, the incidence of newly diagnosed bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders following a diagnosis of symptomatic menopausal transition remained significantly increased in the longer follow-up groups (1-5 and >= 5 years).Symptomatic menopausal transition might increase the risk of subsequent newly onset bipolar disorders, depressive disorders, anxiety disorders, and sleep disorders. A prospective study is necessary to confirm these findings. PMID- 26871844 TI - Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study. AB - Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women. PMID- 26871845 TI - Laparoscopic Anatomical Left Hepatectomy for Intrahepatic Bile Duct Papillary Mucinous Cystadenoma With Intraoperative Vascular Repair: A Case Report. AB - Laparoscopic hepatectomy has been widely performed for patients with benign liver tumors such as hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma.We here present a case of a 78-year-old female patient who was initially admitted to our department due to fever and jaundice for 2 days. Abdominal enhanced computed tomography scan showed intrahepatic and extrahepatic bile duct dilatation with liver atrophy of left lobe. Unenhanced nodules were seen within the left intrahepatic bile duct. Ultrasonography revealed intrahepatic and extrahepatic bile duct dilatation with viscous fluid, tubular adenoma? Tumor markers including alpha fetoprotein, carcinoembryonic antigen, and CA19-9 were normal. Preoperative total bilirubin was 64.4 mmol/L.Laparoscopic anatomical left hepatectomy and common bile duct exploration were performed. In this procedure, a lot of mucus was seen within the common bile duct and left intrahepatic bile duct. No bile duct stones were found after the exploration. During parenchymal transection, intraoperative hemorrhage from middle hepatic vein was met, and we repaired middle hepatic vein by laparoscopic suture (5-0 Prolene). No air embolism and hypotension were met. This operation took 232 minutes and estimated blood loss was 300 mL. Postoperative ultrasonography indicated a normal outflow of middle hepatic vein and there was no stricture. The patient's postoperative course was uneventful and was discharged on the 6th day after surgery. Postoperative pathological diagnosis was intrahepatic bile duct papillary mucinous cystadenoma. PMID- 26871846 TI - The Impact of Creatinine Clearance Rate, Daily Urinary Albumin, and Their Joint Effect on Predicting Death in Diabetic Inpatients After Discharge: An Observational Study. AB - Renal clearance function and urinary albumin excretion are important markers for diabetic nephropathy. We assessed whether the creatinine clearance rate (CCR) and daily urinary albumin (DUA) excretion, which both require 24-hour urine data, are better predictors of mortality in diabetic inpatients compared with the estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR).We enrolled 1011 patients who were hospitalized due to poor glucose control, and collected clinical information, including 24-hour urine data, from their medical records. We determined the mortality rate after discharge by examining the national registry data in Taiwan.The subjects had a median follow-up of 6.5 years (interquartile range between 3.5 and 9.6 years). Subjects with a CCR < 60 mL/min and a DUA >= 300 mg/d had the highest mortality rate, with a hazard ratio of 3.373 (95% confidence interval = 2.469-4.609), compared with the mortality rate in subjects with a CCR >= 60 mL/min and a DUA < 300 mg/d. In terms of predicting mortality in diabetic inpatients, ACR had a similar sensitivity to DUA (40.3% versus 38.0%), but eGFR provided lower sensitivity than CCR (54.5% versus 66.5%).Creatinine clearance rate and DUA have an additive effect on predicting mortality in diabetic inpatients after discharge. Moreover, CCR is a more sensitive predictor of mortality than eGFR. Therefore, determining CCR using 24 hour urine data, as well as either ACR or DUA, should provide better prediction of mortality in diabetic nephropathy patients. PMID- 26871848 TI - Abdominal Kaposiform Hemangioendothelioma Associated With Lymphangiomatosis Involving Mesentery and Ileum: A Case Report of MRI, CT, and 18F-FDG PET/CT Findings. AB - Kaposiform hemangioendothelioma (KH) is a rare vascular tumor of intermediate malignancy that occurs mainly in the childhood. Adult patients with KH are rare. Imaging findings of KH have rarely been reported before. We present magnetic resonance imaging (MRI), computed tomography (CT), and fluorine-18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT findings in an adult patient with KH associated with lymphangiomatosis involving mesentery and ileum.A 22-year-old female complained of a 9-month history of intermittent melena, weakness, and palpitation. Laboratory tests revealed anemia and hypoproteinemia. Fecal occult blood test was positive. Abdominal enhanced MRI and CT showed a large abdominal mass involving mesentery and ileum. On enhanced MRI, there were many hypervascular nodules in the mass. On FDG PET/CT, the mass and the nodules showed slight FDG uptake. Small bowel capsule endoscopy showed numerous grape-shaped red nodules in the luminal wall of the involved ileum. The patient underwent resection of the abdominal mass and a segment of the ileum invaded by the abdominal mass. KH arising within lymphangiomatosis involving mesentery and ileum was confirmed by pathology. After surgery, the patient's symptoms improved.This is the first case of KH associated with lymphangiomatosis involving mesentery and ileum. In this case, the lymphangiomatosis overshadowed the small tumor nodules resulting in unusual imaging findings. Familiarity with these imaging findings is helpful for diagnosis and differential diagnosis of KH. PMID- 26871847 TI - The Effects of Dexmedetomidine on Myocardial Function Assessed by Tissue Doppler Echocardiography During General Anesthesia in Patients With Diastolic Dysfunction: A CONSORT-Prospective, Randomized, Controlled Trial. AB - Dexmedetomidine is a commonly used sedative and adjuvant agent to general anesthesia. The present was designed to evaluate the effects of dexmedetomidine on myocardial function by using tissue Doppler echocardiography during general anesthesia in patients with diastolic dysfunction.Forty patients undergoing orthostatic surgery with ejection fraction preserved diastolic dysfunction grade 2 or 3 were randomly allocated to the Control and Dex group (n = 20, each). In the Dex group, dexmedetomidine was given as an initial loading dose of 1.0 MUg/kg over 10 minutes followed by a maintenance dose of 0.5 MUg/kg/h. The ratio of peak early diastolic transmitral or transtricuspid inflow velocity to early diastolic mitral or tricuspid annular velocity (LV or RV E/e') and left or right ventricular myocardial performance index (LV or RV MPI) were measured at before and after the administration dexmedetomidine or saline.The Dex group showed significant decrease of heart rate (P = 0.038), and increase of mean blood pressure (P < 0.001), LV E/e' (P = 0.025), and LV MPI (P < 0.001) compared to those of the Control group on a linear mixed model analysis. Also, the Dex group showed significant increase of RV E/e' (P < 0.001) and RV MPI (P = 0.028) compared to those of the Control group.Intraoperative dexmedetomidine administration during general anesthesia was appeared to deteriorate biventricular function in patients with diastolic dysfunction. We suggest careful consideration and a need for reducing dosage when administrating dexmedetomidine in patients with diastolic dysfunction. PMID- 26871849 TI - In Acute Myocardial Infarction Liver Parameters Are Associated With Stenosis Diameter. AB - Detection of high-risk subjects in acute myocardial infarction (AMI) by noninvasive means would reduce the need for intracardiac catheterization and associated complications. Liver enzymes are associated with cardiovascular disease risk. A potential predictive value for liver serum markers for the severity of stenosis in AMI was analyzed.Patients with AMI undergoing percutaneous coronary intervention (PCI; n = 437) were retrospectively evaluated. Minimal lumen diameter (MLD) and percent stenosis diameter (SD) were determined from quantitative coronary angiography. Patients were classified according to the severity of stenosis (SD >= 50%, n = 357; SD < 50%, n = 80). Routine heart and liver parameters were associated with SD using random forests (RF). A prediction model (M10) was developed based on parameter importance analysis in RF.Age, alkaline phosphatase (AP), aspartate aminotransferase (AST), and MLD differed significantly between SD >= 50 and SD < 50. Age, AST, alanine aminotransferase (ALT), and troponin correlated significantly with SD, whereas MLD correlated inversely with SD. M10 (age, BMI, AP, AST, ALT, gamma-glutamyltransferase, creatinine, troponin) reached an AUC of 69.7% (CI 63.8-75.5%, P < 0.0001).Routine liver parameters are associated with SD in AMI. A small set of noninvasively determined parameters can identify SD in AMI, and might avoid unnecessary coronary angiography in patients with low risk. The model can be accessed via http://stenosis.heiderlab.de. PMID- 26871850 TI - Predictive Significance of a New Prognostic Score for Patients With Diffuse Large B-Cell Lymphoma in the Interim-Positron Emission Tomography Findings. AB - We hypothesized that the objective treatment response of patients with diffuse large B-cell lymphoma (DLBCL) was affected by many factors such as pathophysiological, biological, and pharmaceutical mechanisms. This retrospective study aimed to evaluate the predictive significance of clinical prognostic factors and interim fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT), and to find a new prognostic predictor significantly associated with DLBCL patients' outcome. A total of 105 adult patients with DLBCL were reviewed. Each patient underwent an interim F-FDG PET/CT scan after the second chemotherapy cycle. The visual method based on the Deauville 5-point scale was used to evaluate the interim-PET/CT scans. The relationships among the prognostic factors, the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were analyzed with Kaplan-Meier plots. The predictive value of the newly constructed prognostic score was analyzed with multivariate analysis (Cox proportional hazard regression model). The visual analysis showed statistically significant differences in both PFS and OS between the patients with a negative interim-PET/CT and those with a positive interim PET/CT. Advanced age, advanced stage, and DLBCL subtype were also significantly associated with outcome. A new prognostic score that composed of the above 4 factors was obtained. New prognostic score stratified patients into 4 risk groups with 3-year PFS of 98.5%, 73.9%, 11.1%, and 0%, and 3-year OS of 100%, 91.3%, 55.6%, and 0% (P < 0.001 for PFS and OS). Multivariate analysis showed that the new prognostic score had the greatest ability to predict relapse (P < 0.001) and death (P < 0.001). In DLBCL patients, interim F-FDG PET/CT can provide significant independent prognostic information. Our work illustrates that the new prognostic score has the strongest potential for accurately prognostication, for stratification in clinical trials, and for design of novel strategies for DLBCL patients in the high-risk group. PMID- 26871851 TI - Tissue Kallikrein Prevents Restenosis After Stenting of Severe Atherosclerotic Stenosis of the Middle Cerebral Artery: A Randomized Controlled Trial. AB - In-stent restenosis (ISR) following intracranial artery stenting affects long term clinical outcome. This randomized controlled trial sought to identify the long-term efficacy of exogenous tissue kallikrein (TK) for preventing ISR after intracranial stenting of symptomatic middle cerebral artery (MCA) atherosclerotic stenosis.Sixty-one patients successfully treated with intracranial stenting for symptomatic MCA M1 segment stenosis (>70%) were enrolled and randomized into 2 groups: control group and TK group. Patients in the TK group received human urinary kallidinogenase for 7 days, followed by maintenance therapy of pancreatic kallikrein for 6 months. The primary end point was angiographically verified ISR at 6 months, and secondary end points included vascular events and death within 12 months. Endogenous TK plasma concentrations of patients were measured before stenting and at the 6-month follow-up time-point.Patients in the TK group had lower occurrence rates of ISR and vascular events than patients in the control group. There was no difference in endogenous TK levels in plasma at 6 months postoperatively between the TK and control groups. Further subgroup analysis revealed that patients without ISR had higher endogenous TK levels at baseline and lower concentrations at 6 months postoperatively compared with patients who underwent ISR.Exogenous TK is effective for the prevention of ISR after intracranial stenting. PMID- 26871852 TI - Depression and the Risk of Myocardial Infarction and Coronary Death: A Meta Analysis of Prospective Cohort Studies. AB - Findings regarding the association between depression and risk of coronary heart disease are inconsistent. We aimed to assess the association between depression and risk of myocardial infarction (MI) and coronary death through a meta analysis.We performed an electronic literature search of MEDLINE, EMBASE, PsycINFO, ISI Web of Science, and Scopus databases through August 1, 2015, and manual search of the references of the eligible papers and related review articles. Two investigators independently conducted study selection and data abstraction. Disagreement was resolved by consensus. Confounder-adjusted hazard ratios (HRs) were pooled using a random-effects model. Heterogeneity was evaluated using the Cochran Q statistic and Higgins index. Publication bias was assessed by funnel plot and Egger test. Study quality was appraised with the Newcastle-Ottawa Scale.Among 19 eligible cohort studies including 323,709 participants, 8447 cases of MI and coronary death were reported during follow-up ranging from 4 to 37 years. The pooled adjusted HRs for patients with depression (vs those without) were 1.22 (95% CI, 1.13-1.32) for combined MI and coronary death, 1.31 (95% CI, 1.09-1.57) for MI alone (9 studies), and 1.36 (95% CI, 1.14 1.63) for coronary death alone (8 studies). The increased risk of MI and coronary death associated with depression was consistent using modified inclusion criteria, across most subgroups, and after adjusting for possible publication bias.Depression is associated with a significantly increased risk of MI and coronary death. Effective prevention and treatment of depression may decrease such risk. PMID- 26871853 TI - Current Safety of Renal Allograft Biopsy With Indication in Adult Recipients: An Observational Study. AB - Renal biopsy remains the golden standard diagnosis of renal function deterioration. The safety in native kidney biopsy is well defined. However, it is a different story in allograft kidney biopsy. We conduct this retrospective study to clarify the safety of allograft kidney biopsy with indication.All variables were grouped by the year of biopsy and they were compared by Mann-Whitney U test (for continuous variables) or Chi-square test (for categorical variables). We collected possible factors associated with complications, including age, gender, body weight, renal function, cause of uremia, status of coagulation, hepatitis, size of needle, and immunosuppressants.We recruited all renal transplant recipients undergoing allograft biopsy between January of 2009 and December of 2014. This is the largest database for allograft kidney biopsy with indication. Of all the 269 biopsies, there was no difference in occurrence among the total 14 complications (5.2%) over these 6 years. There were only 3 cases of hematomas (1.11%), 6 gross hematuria (2.23%), 1 hydronephrosis (0.37%), and 2 hemoglobin decline (0.74%). The outcome of this cohort is the best compared to all other studies, and it is even better than the allograft protocol kidney biopsy. Among all possible factors, patients with pathological report containing "medullary tissue only" were susceptible to complications (P < 0.001, 1.8 of relative risk).In modern era, this study demonstrates the safety of allograft kidney biopsy with indication. Identifying the renal capsule before biopsy to avoid puncture into medulla is the most important element to prevent complications. PMID- 26871854 TI - Thrombocytopenia in Systemic Lupus Erythematosus: Clinical Manifestations, Treatment, and Prognosis in 230 Patients. AB - The aim of the study was to examine the clinical characteristics and prognosis according to severity of thrombocytopenia and response to treatment for thrombocytopenia in patients with systemic lupus erythematosus (SLE).We retrospectively evaluated 230 SLE patients with thrombocytopenia, and reviewed their clinical data and laboratory findings. Thrombocytopenia was defined as platelet counts under 100,000/mm, and patients were divided into 3 thrombocytopenia groups according to severity: mild (platelet counts >50,000/mm), moderate (>20,000/mm, <=50,000/mm), and severe (<=20,000/mm). Clinical characteristics, treatments, and prognoses were compared among the groups. Furthermore, complete remission of thrombocytopenia was defined as platelet counts >100,000/mm after treatment.There was no significant difference in clinical or laboratory findings among the groups according to severity of thrombocytopenia. However, hemorrhagic complications were more frequent in severe thrombocytopenia (P < 0.001) and mortality was also higher (P = 0.001). Complete remission was achieved in 85.2% of patients. The clinical characteristics and modality of treatment did not differ between the patients with and without complete remission. Mortality in patients with complete remission (1.5%) was significantly lower than in those without complete remission (29.4%, P < 0.001). Survival was significantly higher in patients with complete remission from thrombocytopenia (odds ratio = 0.049, 95% confidence interval: 0.013-0.191, P < 0.001).The severity of thrombocytopenia in SLE patients can be a useful independent prognostic factor to predict survival. Moreover, complete remission of thrombocytopenia after treatment is an important prognostic factor. The severity of thrombocytopenia and response to treatment should be closely monitored to predict prognosis in SLE patients. PMID- 26871855 TI - Assessment of Arterial Stiffness, Volume, and Nutritional Status in Stable Renal Transplant Recipients. AB - Reduction of cardiovascular death might have a significant effect on the long term survival rates of renal transplant recipients (RTRs). The aim of the study was to assess the relation between arterial stiffness and graft function, adipose tissue content, and hydration status in patients after kidney transplantation (KTx).The study included 83 RTR patients (mean age: 55 +/- 13 years) who had been admitted to a nephrology-transplantation outpatient clinic 0.5 to 24 years after KTx. Clinical and laboratory data were analyzed and eGFR was calculated with the CKD-EPI formula. Arterial stiffness was assessed in all RTRs with pulse wave propagation velocity (PWV) with the use of a complior device. In addition, fluid and nutritional status was assessed with a Tanita BC 418 body composition analyzer. The control group consisted of 31 hospital workers who received no medication and had no history of cardiovascular disease.Multivariable linear regression analysis, with PWV as a dependent variable, retained the following independent predictors in the final regression model: red blood cell distribution width (RDW) (B = 0.323; P = 0.004), age (B = 0.297; P = 0.005), tacrolimus therapy (B = -0.286; P = 0.004), and central DBP (B = 0.185; P = 0.041). Multivariable linear regression analysis with eGFR as a dependent variable retained the following independent predictors in the final regression model; creatinine concentration (B = -0.632; P = 0.000), hemoglobin (B = 0.280; P = 0.000), CRP (B = -0.172; P = 0.011), tacrolimus therapy (B = 0.142; P = 0.039), and triglycerides (B = -0.142; P = 0.035).Our data indicates that: kidney transplant recipients can present modifiable CVD risk factors linked to increased arterial stiffness, DBP, waist circumference, SCr, time on dialysis, CyA therapy, and visceral fat mass; RDW is a parameter associated with arterial stiffness; and parameters such as CyA therapy, time on dialysis, PWV, RDW, and triglycerides show negative associations with the allograft function assessed with eGFR. PMID- 26871856 TI - Body Mass Index of Young Men in China: Results From Four National Surveys Conducted Between 1955 and 2012. AB - To analyze the characteristics and trends of body mass index (BMI) among young men in China using data from a series of national surveys conducted between 1955 and 2012, and to provide evidence for policy making and disease control and prevention.BMI-related data were collected by routine medical examination from young men, most aged 18 to 20 years, in 4 national surveys (1955, 1974, 2001, and 2012) using a stratified cluster sampling method in 31 provinces, autonomous regions, and municipalities in China. The characteristics and trends of BMI during this period were analyzed by region, year, age, and economic level.Totals of 266,791, 118,092, 69,776, and 57,969 participants were included in the 4 national surveys, respectively. Between 1955 and 2012, height, weight, and BMI showed increasing trends in men aged 18 to 20 years at the national level and in each of the 6 areas of China. BMI also differed among geographical regions. Data from the 2012 national survey showed that age (17-22 years) was correlated positively with the prevalence of overweight and negatively with the prevalence of underweight (both P < 0.05). Gross domestic product was correlated negatively with the prevalence of underweight (r = -0.25) and positively with the prevalence of overweight and obesity (r = 0.45 and 0.240, respectively; all P < 0.001).BMI increased with economic development among young men from 1955 to 2012, with distinct variation among geographic areas in China. Although underweight remains prevalent in young men, especially in urban and northern regions, overweight and obesity are increasingly prevalent and warrant public health attention. PMID- 26871857 TI - Serum Calcium Concentration Is Inversely Associated With Radiographic Knee Osteoarthritis: A Cross-Sectional Study. AB - To examine the relationship between serum calcium (Ca) concentration and radiographic knee osteoarthritis (OA).This study covered a total of 2855 subjects. The serum Ca concentration was detected by the Arsenazo III method. The radiographic OA of the knee was defined as changes equivalent to Kellgren Lawrence grade 2 on 1 side at least. The serum Ca concentration was categorized into 4 quartiles, which are <=2.27, 2.28-2.34, 2.35-2.41, and >=2.42 mmol/L, respectively. The relationship between serum Ca and radiographic knee OA was examined using the multivariable logistic analysis after adjusting a series of potential confounding factors. For each quartile of the relationship between serum Ca concentration and radiographic knee OA, the OR with 95% CI was calculated, and the one with the lowest value was considered to be the reference.An inverse association existed between serum Ca concentration and radiographic OA of the knee in the multivariable model and the model where the factors of age, sex, and BMI were adjusted. The multivariable-adjusted OR (95% CI) for radiographic knee OA in the second, third, and fourth quartiles of serum Ca concentration were 1.05 (95% CI: 0.83-1.31), 1.01 (95% CI: 0.80-1.27), and 0.79 (95% CI: 0.62-1.00), respectively, in comparison with the reference (first) quartile. A trend approaching to statistical significant (P = 0.06) was observed. Meanwhile, the relative odds of radiographic OA of the knee were decreased by 0.79 times in the fourth quartile in comparison with the reference.There is likely to be an inverse association between serum Ca concentration and radiographic OA of the knee. PMID- 26871858 TI - Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study. AB - The aim of this study was to evaluate the risk of depression in and effect of L thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18-2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66 1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression. PMID- 26871859 TI - Association Between 3 IL-10 Gene Polymorphisms and Cardiovascular Disease Risk: Systematic Review With Meta-Analysis and Trial Sequential Analysis. AB - Previous studies have yielded controversial results related to the contribution of interleukin 10 (IL-10) gene polymorphisms (IL-10 -592C/A, IL-10 -1082G/A, and IL-10 -819C/T) in the progression of cardiovascular disease (CVD). Thus, we performed a meta-analysis to summarize this situation.Eligible studies were retrieved by searching PubMed, Embase, Web of Science, and Cochrane Library with the last search up to July 7, 2015. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). False-positive report probability (FPRP) analysis was conducted for all significant findings. Genotype-based mRNA expression analysis was also performed using data from 270 individuals with different ethnicities.Finally, 19 studies for IL-10 -592C/A polymorphism (7284 cases and 7469 controls), 21 studies for IL-10 -1082G/A polymorphism (8263 cases and 5765 controls), and 12 studies for IL-10 -819C/T polymorphism (4502 cases and 3190 controls) were included in the meta-analyses. With respect to IL-10 -819C/T polymorphism, statistically significant decreased CVD risk was found when all studies were pooled into the meta-analysis (T vs C: OR = 0.91, 95% CI = 0.84 0.98; TT + TC vs CC: OR = 0.90, 95% CI = 0.81-1.00). Subgroup analyses stratified by disease subtype suggested the -819C/T polymorphism was significantly associated with a decreased CAD risk (T vs C: OR = 0.90, 95% CI = 0.83-0.97; TT vs CC: OR = 0.81, 95% CI = 0.66-1.00; TT vs TC + CC: OR = 0.82, 95% CI = 0.69 0.98; TT + TC vs CC: OR = 0.89, 95% CI = 0.80-0.99), which was noteworthy finding as evaluated by FPRP. However, with regard to IL-10 -592C/A and IL-10 -1082G/A polymorphisms, no significant association with CVD risk was observed in the overall and subgroup analyses.In conventional meta-analyses, the results suggested that IL-10 -819C/T polymorphism was associated with decreased risk of CVD, especially CAD outcome, whereas IL-10 -592C/A and IL-10 -1082G/A polymorphisms might have no influence on the susceptibility of CVD. However, trial sequential analysis does not allow us to draw any solid conclusion for the association between IL-10 -592C/A or IL-10 -1082G/A polymorphism and CVD risk. Further large and well-designed studies are still needed. PMID- 26871861 TI - Synergistic Action of IL-8 and Bone Marrow Concentrate on Cartilage Regeneration Through Upregulation of Chondrogenic Transcription Factors. AB - The objective of this study was to determine whether a biphasic scaffold loaded with a combination of a chemokine and bone marrow concentrate (BMC) could improve tissue regeneration in knee articular cartilage of beagles with cylindrical osteochondral defects. For this investigation, an osteochondral defect (6 mm in diameter and 8 mm deep) was created in the weight-bearing articular surface of the femoral medial condyle in beagles. Bone marrow was aspirated from the posterior iliac crests of beagles to obtain mesenchymal stem cells (MSCs) for in vitro assay. Hematoxylin and eosin (HE), Masson's trichrome (MT), safranin O/fast green staining, and immunohistochemistry were performed for histological analysis. Quantitative real-time polymerase chain reaction was performed to understand the roles of BMC in chondrogenic differentiation of MSCs. At 12 weeks after transplantation of biphasic scaffolds, we observed that interleukin-8 (IL 8) or the combination of IL-8 and BMC induced massive bone regeneration compared to saline, BMC only, and MSCs. In gross appearance, the osteochondral defect site was nearly completely filled with repair tissue in the group that received the combination of IL-8 and BMC but not in the other groups. Moreover, histological analysis showed obvious differences in cartilage regeneration among groups. HE and MT staining showed that the cartilage defect sites of the group receiving the combination of IL-8 and BMC were regenerated with cartilage-like tissues showing chondrocyte morphology. Safranin O staining showed hyaline cartilage regeneration in the group receiving IL-8 and BMC, whereas fibrous-like tissues were formed in the other groups. Furthermore, immunostaining revealed the presence of type II collagen and aggrecan in regenerated cartilage tissue of the group receiving IL-8 and BMC, whereas regenerated cartilage tissues of the other groups weakly expressed type II collagen and aggrecan. These results indicate that the combination of a chemokine IL-8 and BMC has significant positive effects on osteochondral regeneration in a beagle model through enhancing expression of the chondrogenic transcription factors and markers such as Sox9 and type II collagen. PMID- 26871860 TI - Adipose-Derived Stem Cell-Seeded Hydrogels Increase Endogenous Progenitor Cell Recruitment and Neovascularization in Wounds. AB - Adipose-derived mesenchymal stem cells (ASCs) are appealing for cell-based wound therapies because of their accessibility and ease of harvest, but their utility is limited by poor cell survival within the harsh wound microenvironment. In prior work, our laboratory has demonstrated that seeding ASCs within a soft pullulan-collagen hydrogel enhances ASC survival and improves wound healing. To more fully understand the mechanism of this therapy, we examined whether ASC seeded hydrogels were able to modulate the recruitment and/or functionality of endogenous progenitor cells. Employing a parabiosis model and fluorescence activated cell sorting analysis, we demonstrate that application of ASC-seeded hydrogels to wounds, when compared with injected ASCs or a noncell control, increased the recruitment of provascular circulating bone marrow-derived mesenchymal progenitor cells (BM-MPCs). BM-MPCs comprised 23.0% of recruited circulating progenitor cells in wounds treated with ASC-seeded hydrogels versus 8.4% and 2.1% in those treated with controls, p < 0.05. Exploring the potential for functional modulation of BM-MPCs, we demonstrate a statistically significant increase in BM-MPC migration, proliferation, and tubulization when exposed to hydrogel-seeded ASC-conditioned medium versus control ASC-conditioned medium (73.8% vs. 51.4% scratch assay closure; 9.1% vs. 1.4% proliferation rate; 10.2 vs. 5.5 tubules/HPF; p < 0.05 for all assays). BM-MPC expression of genes related to cell stemness and angiogenesis was also significantly increased following exposure to hydrogel-seeded ASC-conditioned medium (p < 0.05). These data suggest that ASC-seeded hydrogels improve both progenitor cell recruitment and functionality to effect greater neovascularization. PMID- 26871862 TI - Coculturing Human Islets with Proangiogenic Support Cells to Improve Islet Revascularization at the Subcutaneous Transplantation Site. AB - While subcutaneous tissue has been proposed as a clinically relevant site for pancreatic islet transplantation, a major issue of concern remains, which is its poor vascular state. In an effort to overcome this limitation, we present an efficient and reproducible method to form human composite islets (CIs) with proangiogenic cell types in a controlled manner using nonadherent agarose microwell templates. In this study, we assessed the three-dimensional structure, function, and angiogenic potential of human CIs with human mesenchymal stromal cells (hMSCs), with or without human umbilical vein endothelial cells (HUVECs), and preconditioned hMSCs (PC-hMSCs) in EGM-2 under shear stress. Distinct cellular rearrangements could be observed in CIs, but islet functionality was maintained. In vitro angiogenesis assays found significantly enhanced sprout formation in case of CIs. In particular, the number of sprouts emanating from CIs with PC-hMSCs was significantly increased compared to other conditions. Subsequent in vivo assessment confirmed the proangiogenic potential of CIs. However, in contrast to our in vitro angiogenesis assays, CIs with hMSCs and HUVECs exhibited a higher in vivo angiogenic potential compared to control islets or islets combined with hMSCs or PC-hMSCs. These findings highlight the importance and necessity of verifying in vitro studies with in vivo models to reliably predict, in this case, revascularization outcomes. Regardless, we demonstrate here the therapeutic potential of CIs with proangiogenic support cells to enhance islet revascularization at a clinically relevant, although poorly vascularized, transplantation site. PMID- 26871864 TI - Enhanced Electrocatalytic Activities of PtCuCoNi Three-Dimensional Nanoporous Quaternary Alloys for Oxygen Reduction and Methanol Oxidation Reactions. AB - Control of morphology and composition could precisely and efficiently alter the catalytic properties of Pt-based materials, improving the electrocatalytic activity and durability. Here we proposed a rapid, controllable synthesis of three-dimensional PtCuCoNi quaternary alloys with low Pt-group metal, which were directly synthesized by reducing metal precursors in aqueous solution. The resultant quaternary alloys show excellent oxygen reduction and methanol oxidation reaction activities in acid solution. By rational tuning of the composition of PtCuCoNi alloys, they achieved a mass activity of 0.72 A/mgPt on the basis of Pt mass for oxygen reduction reaction. Moreover, the durability is also higher than that of commercial Pt/C catalyst. These PtCuCoNi quaternary alloys characterized by three-dimensional porous nanostructures hold attractive promise as substitutes for carbon-supported Pt catalysts with improved activity and stability. PMID- 26871865 TI - Immobilization and electrochemical properties of ruthenium and iridium complexes on carbon electrodes. AB - We report the synthesis and surface immobilization of two new pyrene-appended molecular metal complexes: a ruthenium tris(bipyridyl) complex (1) and a bipyridyl complex of [Cp*Ir] (2) (Cp* = pentamethylcyclopentadienyl). X-ray photoelectron spectroscopy confirmed successful immobilization on high surface area carbon electrodes, with the expected elemental ratios for the desired compounds. Electrochemical data collected in acetonitrile solution revealed a reversible reduction of 1 near -1.4 V, and reduction of 2 near -0.75 V. The noncovalent immobilization, driven by association of the appended pyrene groups with the surface, was sufficiently stable to enable studies of the molecular electrochemistry. Electroactive surface coverage of 1 was diminished by only 27% over three hours soaking in electrolyte solution as measured by cyclic voltammetry. The electrochemical response of 2 resembled its soluble analogues, and suggested that ligand exchange occurred on the surface. Together, the results demonstrate that noncovalent immobilization routes are suitable for obtaining fundamental understanding of immobilized metal complexes and their reductive electrochemical properties. PMID- 26871863 TI - Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement. AB - Cartilage has a poor healing response, and few viable options exist for repair of extensive damage. Hyaluronic acid (HA) hydrogels seeded with mesenchymal stem cells (MSCs) polymerized through UV crosslinking can generate functional tissue, but this crosslinking is not compatible with indirect rapid prototyping utilizing opaque anatomic molds. Methacrylate-modified polymers can also be chemically crosslinked in a cytocompatible manner using ammonium persulfate (APS) and N,N,N',N'-tetramethylethylenediamine (TEMED). The objectives of this study were to (1) compare APS/TEMED crosslinking with UV crosslinking in terms of functional maturation of MSC-seeded HA hydrogels; (2) generate an anatomic mold of a complex joint surface through rapid prototyping; and (3) grow anatomic MSC-seeded HA hydrogel constructs using this alternative crosslinking method. Juvenile bovine MSCs were suspended in methacrylated HA (MeHA) and crosslinked either through UV polymerization or chemically with APS/TEMED to generate cylindrical constructs. Minipig porcine femoral heads were imaged using microCT, and anatomic negative molds were generated by three-dimensional printing using fused deposition modeling. Molded HA constructs were produced using the APS/TEMED method. All constructs were cultured for up to 12 weeks in a chemically defined medium supplemented with TGF-beta3 and characterized by mechanical testing, biochemical assays, and histologic analysis. Both UV- and APS/TEMED-polymerized constructs showed increasing mechanical properties and robust proteoglycan and collagen deposition over time. At 12 weeks, APS/TEMED-polymerized constructs had higher equilibrium and dynamic moduli than UV-polymerized constructs, with no differences in proteoglycan or collagen content. Molded HA constructs retained their hemispherical shape in culture and demonstrated increasing mechanical properties and proteoglycan and collagen deposition, especially at the edges compared to the center of these larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement. PMID- 26871867 TI - Pathway Analysis of Proteomics Profiles in Rabies Infection: Towards Future Biomarkers? AB - Rabies is a zoonotic viral disease that invariably leads to fatal encephalitis, which can be prevented provided post-exposure prophylaxis is initiated timely. Ante-mortem diagnostic tests are inconclusive, and rabies is nontreatable once the clinical signs appear. A large number of host factors are responsible for the altered neuronal functions observed in rabies; however their precise role remains uninvestigated. We therefore used two-dimensional electrophoresis and mass spectrometry analysis to identify differentially expressed host proteins in an experimental murine model of rabies. We identified 143 proteins corresponding to 45 differentially expressed spots (p < 0.05) in neuronal tissues of Swiss albino mice in response to infection with neurovirulent rabies strains. Time series analyses revealed that a majority of the alterations occur at 4 to 6 days post infection, in particular affecting the host's cytoskeletal architecture. Extensive pathway analysis and protein interaction studies using the bioinformatic tools such as Ingenuity Pathway Analysis and STRING revealed novel pathways and molecules (e.g., protein ubiquitination) unexplored hitherto. Further activation/inhibition studies of these pathway molecular leads would be relevant to identify novel biomarkers and mechanism-based therapeutics for rabies, a disease that continues to severely impact global health. PMID- 26871866 TI - Picoplankton Bloom in Global South? A High Fraction of Aerobic Anoxygenic Phototrophic Bacteria in Metagenomes from a Coastal Bay (Arraial do Cabo- Brazil). AB - Marine habitats harbor a great diversity of microorganism from the three domains of life, only a small fraction of which can be cultivated. Metagenomic approaches are increasingly popular for addressing microbial diversity without culture, serving as sensitive and relatively unbiased methods for identifying and cataloging the diversity of nucleic acid sequences derived from organisms in environmental samples. Aerobic anoxygenic phototrophic bacteria (AAP) play important roles in carbon and energy cycling in aquatic systems. In oceans, those bacteria are widely distributed; however, their abundance and importance are still poorly understood. The aim of this study was to estimate abundance and diversity of AAPs in metagenomes from an upwelling affected coastal bay in Arraial do Cabo, Brazil, using in silico screening for the anoxygenic photosynthesis core genes. Metagenomes from the Global Ocean Sample Expedition (GOS) were screened for comparative purposes. AAPs were highly abundant in the free-living bacterial fraction from Arraial do Cabo: 23.88% of total bacterial cells, compared with 15% in the GOS dataset. Of the ten most AAP abundant samples from GOS, eight were collected close to the Equator where solar irradiation is high year-round. We were able to assign most retrieved sequences to phylo-groups, with a particularly high abundance of Roseobacter in Arraial do Cabo samples. The high abundance of AAP in this tropical bay may be related to the upwelling phenomenon and subsequent picoplankton bloom. These results suggest a link between upwelling and light abundance and demonstrate AAP even in oligotrophic tropical and subtropical environments. Longitudinal studies in the Arraial do Cabo region are warranted to understand the dynamics of AAP at different locations and seasons, and the ecological role of these unique bacteria for biogeochemical and energy cycling in the ocean. PMID- 26871868 TI - An Improved Molecular Histology Method for Ion Suppression Monitoring and Quantification of Phosphatidyl Cholines During MALDI MSI Lipidomics Analyses. AB - Tissue lipidomics is one of the latest omics approaches for biomarker discovery in pharmacology, pathology, and the life sciences at large. In this context, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is the most versatile tool to map compounds within tissue sections. However, ion suppression events occurring during MALDI MSI analyses make it impossible to use this method for quantitative investigations without additional validation steps. This is especially true for lipidomics, since different lipid classes are responsible for important ion suppression events. We propose here an improved lipidomics method to assess local ion suppression of phospatidylcholines in tissues. Serial tissue sections were spiked with different amounts of PC(16:0 d31/18:1) using a nebulization device. Settings for standard nebulization were strictly controlled for a detection similar to when using spiked tissue homogenates. The sections were simultaneously analyzed by MALDI MSI using a Fourier transform ion cyclotron resonance analyzer. Such a spray-based approach allows taking into account the biochemical heterogeneity of the tissue for the detection of PC(16:0 d31/18:1). Thus, here we present the perspective to use this method for quantification purposes. The linear regression lines are considered as calibration curves and we calculate PC(16:0/18:1) quantification values for different ROIs. Although those values need to be validated by a using a different independent approach, the workflow offers an insight into new quantitative mass spectrometry imaging (q-MSI) methods. This approach of ion suppression monitoring of phosphocholines in tissues may be highly interesting for a large range of applications in MALDI MSI, particularly for pathology using translational science workflows. PMID- 26871869 TI - The JMJD3 Histone Demethylase and the EZH2 Histone Methyltransferase in Prostate Cancer. PMID- 26871870 TI - Do Referral Patterns in Adolescents and Young Adults with Testicular Cancer Impact Oncologic Outcomes? AB - PURPOSE: Oncologic outcomes in advanced testicular cancer (TC) depend on appropriate and timely care. Often this care is referred to tertiary academic medical centers (AMCs). The aim of this study was to compare oncologic outcomes of adolescent and young adult (AYA) patients with TC treated from the outset at an AMC to those whose care was initiated elsewhere with subsequent referral. METHODS: An institutional TC database was reviewed, and those AYA patients initiating TC care either inside or outside an AMC were compared. Patients were classified as initiating care outside if they had any non-orchiectomy surgery, chemotherapy, or radiotherapy for TC outside an AMC. RESULTS: A total of 183 patients were reviewed, of whom 59 initiated TC care outside and 124 were managed initially at an AMC. Patients initiating care outside were more likely to have non-seminoma histology and more often presented with metastatic disease (Stage II [30.5%] or III [35.6%] vs. Stage II [19.4%] or III [19.4%]; p = 0.007). Lower 3 year event-free survival (EFS) was observed in those initiating treatment outside an AMC (60.6% vs. 78.7%; p = 0.027). However, on multivariate analysis adjusting for stage and histology, the location of initiating TC care was no longer significant (hazard ratio = 1.5, 95% confidence interval 0.8-2.9). CONCLUSION: AYA patients initially treated for TC in the community and subsequently referred to an AMC were initially observed to experience worse EFS than those who were managed at an AMC from the outset. However, on multivariate analysis, these findings were largely explained by referral bias, where AYA patients with advanced disease were more likely to be referred to AMCs. PMID- 26871873 TI - Understanding the Relationship Between Exergame Play Experiences, Enjoyment, and Intentions for Continued Play. AB - OBJECTIVE: Although it is generally understood that exergames can be beneficial, more research is needed to understand how in-game experiences influence enjoyment and the likelihood for continued use of these types of games. Therefore, the objective of this research is to understand how player performance in an exergame affects psychological responses (autonomy, competence, and presence), enjoyment of the experience, and likelihood for future play. SUBJECTS AND METHODS: Sixty two college students (mean age, 20.32 years) participated in an experiment where they played a challenge event on the "Biggest Loser" exergame for the Nintendo (Kyoto, Japan) WiiTM console. Participants were given up to two chances to see if they could "win" the challenge event. A lab assistant recorded player performance for each session in minutes and seconds (range, 30 seconds-10 minutes). The attempt in which the participant achieved the greatest amount of time playing was used as a measure of player performance. After playing, subjects filled out a questionnaire with items pertaining to enjoyment, competence, autonomy, presence, and future intentions for continued use of the exergame. RESULTS: The results suggest that player achievement (longer time spent playing) directly and indirectly predicts feelings of autonomy, competence, presence, enjoyment, and future intentions to play. Individuals who performed better felt more autonomous and experienced greater presence, leading to greater enjoyment. Enjoyment and presence were found to mediate the relationship between player performance and future intentions to play an exergame. CONCLUSIONS: This study suggests that performance in exergames is related to psychological experiences that fuel enjoyment and the likelihood for future exergame use. The theoretical and practical significances of these findings are discussed, as well as future research involving exergames. PMID- 26871874 TI - Characterization of a bacterioruberin-producing Haloarchaea isolated from the marshlands of the Odiel river in the southwest of Spain. AB - In this work, we describe the isolation, identification, pigment characterization, and optimization of the culture conditions for a haloarchaea strain isolated from salt evaporation ponds in the Odiel river, at Southwest of Spain. The haloarchaea belongs to the genus Halorobrum, as deduced from the analysis of its 16S rRNA encoding gene and has been designated as Halorubrum sp. SH1. The growth conditions for the new strain were optimized studying temperature, NaCl concentration, agitation rate and light intensity. The C50 carotenoids, bacterioruberin, and its derivatives bisanhydrobacterioruberin and trisanhydrobacterioruberin, were found to be the predominant pigments produced by this strain of Halorubrum, as determined using HPLC-DAD and UHPLC-ESI-MS/MS techniques. This extremely halophilic archaeon could be a good candidate for the production of bacterioruberins of high added-value due to their coloring, antioxidant, and possible anticancer properties. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:592-600, 2016. PMID- 26871875 TI - Protecting Future Children from In-Utero Harm. AB - The actions of pregnant women can cause harm to their future children. However, even if the possible harm is serious and likely to occur, the law will generally not intervene. A pregnant woman is an autonomous person who is entitled to make her own decisions. A fetus in-utero has no legal right to protection. In striking contrast, the child, if born alive, may sue for injury in-utero; and the child is entitled to be protected by being removed from her parents if necessary for her protection. Indeed, there is a legal obligation for health professionals to report suspected harm, and for authorities to protect the child's wellbeing. We ask whether such contradictory responses are justified. Should the law intervene where a pregnant woman's actions risk serious and preventable fetal injury? The argument for legal intervention to protect a fetus is sometimes linked to the concept of 'fetal personhood' and the moral status of the fetus. In this article we will suggest that even if the fetus is not regarded as a separate person, and does not have the legal or moral status of a child, indeed, even if the fetus is regarded as having no legal or moral status, there is an ethical and legal case for intervening to prevent serious harm to a future child. We examine the arguments for and against intervention on behalf of the future child, drawing on the example of excessive maternal alcohol intake. PMID- 26871876 TI - Using the Digits-In-Noise Test to Estimate Age-Related Hearing Loss. AB - OBJECTIVE: Age-related hearing loss is common in the elderly population. Timely detection and targeted counseling can lead to adequate treatment with hearing aids. The Digits-In-Noise (DIN) test was developed as a relatively simple test to assess hearing acuity. It is a potentially powerful test for the screening of large populations, including the elderly. However, until to date, no sensitivity or specificity rates for detecting hearing loss were reported in a general elderly population. The purpose of this study was to evaluate the ability of the DIN test to screen for mild and moderate hearing loss in the elderly. DESIGN: Data of pure-tone audiometry and the DIN test were collected from 3327 adults ages above 50 (mean: 65), as part of the Rotterdam Study, a large population based cohort study. Sensitivity and specificity of the DIN test for detecting hearing loss were calculated by comparing speech reception threshold (SRT) with pure-tone average threshold at 0.5, 1, 2, and 4 kHz (PTA0.5,1,2,4). Receiver operating characteristics were calculated for detecting >20 and >35 dB HL average hearing loss at the best ear. RESULTS: Hearing loss varied greatly between subjects and, as expected, increased with age. High frequencies and men were more severely affected. A strong correlation (R = 0.80, p < 0.001) was found between SRTs and PTA0.5,1,2,4. Moreover, 65% of variance in SRT could be explained by pure-tone thresholds. For detecting mild or moderate hearing loss, receiver operating characteristics showed areas under the curve of 0.86 and 0.98, respectively. CONCLUSIONS: This study demonstrates that the DIN test has excellent test characteristics when screening for moderate hearing loss (or more) in an elderly population. It is less suited to screen for mild hearing loss. The test is easy to complete and should be suitable for implementation as an automated self-test in hearing screening programs. Ultimately, when combined with active counseling, hearing screening could lead to higher hearing aid coverage in the hearing impaired elderly. PMID- 26871877 TI - Effects of Negative Middle Ear Pressure on Wideband Acoustic Immittance in Normal Hearing Adults. AB - OBJECTIVES: Wideband acoustic immittance (WAI) measurements are capable of quantifying middle ear performance over a wide range of frequencies relevant to human hearing. Static pressure in the middle ear cavity affects sound transmission to the cochlea, but few datasets exist to quantify the relationship between middle ear transmission and the static pressure. In this study, WAI measurements of normal ears are analyzed in both negative middle ear pressure (NMEP) and ambient middle ear pressure (AMEP) conditions, with a focus on the effects of NMEP in individual ears. DESIGN: Eight subjects with normal middle ear function were trained to induce consistent NMEPs, quantified by the tympanic peak pressure (TPP) and WAI. The effects of NMEP on the wideband power absorbance level are analyzed for individual ears. Complex (magnitude and phase) WAI quantities at the tympanic membrane (TM) are studied by removing the delay due to the residual ear canal (REC) volume between the probe tip and the TM. WAI results are then analyzed using a simplified classical model of the middle ear. RESULTS: For the 8 ears presented here, NMEP has the largest and most significant effect across ears from 0.8 to 1.9 kHz, resulting in reduced power absorbance by the middle ear and cochlea. On average, NMEP causes a decrease in the power absorbance level for low- to mid-frequencies, and a small increase above about 4 kHz. The effects of NMEP on WAI quantities, including the absorbance level and TM impedance, vary considerably across ears. The complex WAI at the TM and fitted model parameters show that NMEP causes a decrease in the aggregate compliance at the TM. Estimated REC delays show little to no dependence on NMEP. CONCLUSIONS: In agreement with previous results, these data show that the power absorbance level is most sensitive to NMEP around 1 kHz. The REC effect is removed from WAI measurements, allowing for direct estimation of complex WAI at the TM. These estimates show NMEP effects consistent with an increased stiffness in the middle ear, which could originate from the TM, tensor tympani, annular ligament, or other middle ear structures. Model results quantify this nonlinear, stiffness related change in a systematic way, that is not dependent on averaging WAI results in frequency bands. Given the variability of pressure effects, likely related to intersubject variability at AMEP, TPP is not a strong predictor of change in WAI at the TM. More data and modeling will be needed to better quantify the relationship between NMEP, WAI, and middle ear transmission. PMID- 26871878 TI - Vinegar-amended anaerobic biosand filter for the removal of arsenic and nitrate from groundwater. AB - The performance of a vinegar-amended anaerobic biosand filter was evaluated for future application as point-of-use water treatment in rural areas for the removal of arsenic and nitrate from groundwater containing common ions. Due to the importance of sulfate and iron in arsenic removal and their variable concentrations in groundwater, influent sulfate and iron concentrations were varied. Complete removal of influent nitrate (50 mg/L) and over 50% removal of influent arsenic (200 MUg/L) occurred. Of all conditions tested, the lowest median effluent arsenic concentration was 88 MUg/L. Iron removal occurred completely when 4 mg/L was added, and sulfate concentrations were lowered to a median concentration <2 mg/L from influent concentrations of 22 and 50 mg/L. Despite iron and sulfate removal and the establishment of reducing conditions, arsenic concentrations remained above the World Health Organization's arsenic drinking water standard. Further research is necessary to determine if anaerobic biosand filters can be improved to meet the arsenic drinking water standard and to evaluate practical implementation challenges. PMID- 26871879 TI - Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes. AB - RATIONALE: We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. OBJECTIVES: To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS: A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. MEASUREMENTS AND MAIN RESULTS: Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). CONCLUSIONS: The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145). PMID- 26871880 TI - Factors Affecting Women's Autonomous Decision Making In Research Participation Amongst Yoruba Women Of Western Nigeria. AB - Research is a global enterprise requiring participation of both genders for generalizable knowledge; advancement of science and evidence based medical treatment. Participation of women in research is necessary to reduce the current bias that most empirical evidence is obtained from studies with men to inform health care and related policy interventions. Various factors are assumed to limit autonomy amongst the Yoruba women of western Nigeria. This paper seeks to explore the experience and understanding of autonomy by the Yoruba women in relation to research participation. Focus is on factors that affect women's autonomous decision making in research participation. An exploratory qualitative approach comprising four focus group discussions, 42 in-depth interviews and 14 key informant interviews was used. The study permits a significant amount of triangulation, as opinions of husbands and religious leaders are also explored. Interviews and discussions were audiotaped and transcribed verbatim. Content analysis was employed for data analysis. Findings show that concepts of autonomy varied amongst the Yoruba women. Patriarchy, religion and culture are conceived to have negative impact on the autonomy of women in respect to research participation. Among the important findings are: 1) male dominance is strongly emphasized by religious leaders who should teach equality, 2) while men feel that by making decisions for women, they are protecting them, the women on the other hand see this protection as a way of limiting their autonomy. We recommend further studies to develop culturally appropriate and workable recruitment methods to increase women's participation in research. PMID- 26871883 TI - Modeling closure of circular wounds through coordinated collective motion. AB - Wound healing enables tissues to restore their original states, and is achieved through collective cell migration into the wound space, contraction of the wound edge via an actomyosin filament 'purse-string,' as well as cell division. Recently, experimental techniques have been developed to create wounds with various regular morphologies in epithelial monolayers, and these experiments of circular closed-contour wounds support coordinated lamellipodial cell crawling as the predominant driver of gap closure. Through utilizing a particle-based mechanical tissue simulation, exhibiting long-range coordination of cell motility, we computationally model these closed-contour experiments with a high level of agreement between experimentally observed and simulated wound closure dynamics and tissue velocity profiles. We also determine the sensitivity of wound closure time in the model to changes in cell motility force and division rate. Our simulation results confirm that circular wounds can close due to collective cell migration without the necessity for a purse-string mechanism or for cell division, and show that the alignment mechanism of cellular motility force with velocity, leading to collective motion in the model, may speed up wound closure. PMID- 26871884 TI - Gambling involvement indicative of underlying behavioral and mental health disorders. AB - BACKGROUND AND OBJECTIVES: In spite of increased gambling opportunities, risk factors associated with recreational gambling remain poorly understood. This study assessed behavioral risk factors associated with frequency of recreational gambling. METHODS: Data were derived from the 2013 Massachusetts Behavioral Risk Factor Surveillance System. Gambling frequency was divided into two or more times per week, 1-4 times a month, less than 10 times in total, and not at all. Health risk behaviors included smoking, drinking, obesity, seat belt use, and sleep patterns. Multivariate logistic regression was used to assess relationships between overall gambling participation and gambling frequency and behavioral risk behaviors. Final analytical sample included 3,988 survey respondents. Statistical analyses were performed using STATA. RESULTS: Significant differences exist in the socio-demographic characteristics of recreational gamblers. Highest gambling frequency is associated with increased odds of alcohol consumption (ie, having at least one alcohol drink during the past 30 days) (OR 1.9; p < .05), binge drinking (ie, having five or more alcohol drinks at least once during the past 30 days) (OR 3.7; p < .001), and tobacco use (ie, having smoked at least 100 cigarettes in a lifetime) (OR 3.4; p < .001). The odds of having fourteen days of poor mental health are twofold for recreational gamblers who gamble two or more times per week (OR 2.2; p < .05). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Differing behavioral and mental health risk factors emerge among recreational gamblers by gambling frequency. Gambling frequency may be a better proxy for assessing the risk of developing gambling related behavioral disorders than overall endorsement of gambling participation. PMID- 26871882 TI - Male Clients of Male Sex Workers in China: An Ignored High-Risk Population. AB - BACKGROUND: There is a high prevalence of HIV/syphilis among male sex workers, but no formal study has ever been conducted focusing on male clients of male sex workers (MCM). A detailed investigation was thus called for, to determine the burden and sociobehavioral determinants of HIV and syphilis among these MCM in China. METHODS: As part of a multicenter cross-sectional study, using respondent driven and snowball sampling, 2958 consenting adult men who have sex with men (MSM) were recruited, interviewed, and tested for HIV and syphilis between 2008 and 2009. The distributions of sociodemographic characteristics, risk behaviors, and HIV/syphilis prevalence were determined and compared between MCM and other MSM. RESULTS: Among recruited MSM, 5.0% (n = 148) were MCM. HIV prevalences for MCM and other MSM were 7.4% and 7.7%, whereas 18.9% and 14.0% were positive for syphilis, respectively. Condomless anal intercourse (CAI) was reported by 59.5% of MCM and 48.2% of MSM. Multiple logistic regression revealed that compared with other MSM, MCM were more likely to have less education [for <= elementary level, adjusted odds ratio (aOR) = 3.13, 95% confidence interval (95% CI): 1.42 to 6.90], higher income (for >500 US Dollars per month, aOR = 2.97, 95% CI: 1.53 to 5.77), more often found partners at parks/restrooms (aOR = 4.01, 95% CI: 2.34 to 6.85), reported CAI (aOR = 1.49, 95% CI: 1.05 to 2.10), reported a larger sexual network (for >= 10, aOR = 2.70, 95% CI: 1.44 to 5.07), and higher odds of syphilis (aOR = 1.54, 95% CI: 1.00 to 2.38). CONCLUSIONS: The greater frequency of risk behaviors and high prevalence of HIV and syphilis indicated that HIV/syphilis prevention programs in China need to pay special attention to MCM as a distinct subgroup, which was completely ignored until date. PMID- 26871881 TI - Discontinuation of Initial Antiretroviral Therapy in Clinical Practice: Moving Toward Individualized Therapy. AB - BACKGROUND: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. METHODS: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of >= 1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. RESULTS: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4 cell (P = 0.011), and higher lymphocyte T CD8 cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). CONCLUSIONS: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity. PMID- 26871885 TI - Musical molecules: the molecular junction as an active component in audio distortion circuits. AB - Molecular junctions that have a non-linear current-voltage characteristic consistent with quantum mechanical tunneling are demonstrated as analog audio clipping elements in overdrive circuits widely used in electronic music, particularly with electric guitars. The performance of large-area molecular junctions fabricated at the wafer level is compared to currently standard semiconductor diode clippers, showing a difference in the sound character. The harmonic distributions resulting from the use of traditional and molecular clipping elements are reported and discussed, and differences in performance are noted that result from the underlying physics that controls the electronic properties of each clipping component. In addition, the ability to tune the sound using the molecular junction is demonstrated. Finally, the hybrid circuit is compared to an overdriven tube amplifier, which has been the standard reference electric guitar clipped tone for over 60 years. In order to investigate the feasibility of manufacturing molecular junctions for use in commercial applications, devices are fabricated using a low-density format at the wafer level, where 38 dies per wafer, each containing two molecular junctions, are made with exceptional non-shorted yield (99.4%, representing 718 out of 722 tested devices) without requiring clean room facilities. PMID- 26871886 TI - Kinetic analysis of nanoparticle-protein interactions using a plasmon waveguide resonance. AB - A plasmon waveguide resonance (PWR) sensor is proposed for studying the interaction between gold nanoparticles and proteins. The ability of the PWR sensor to operate in both TM and TE Polarizations, i.e. its polarization diversity, facilitates the simultaneous spectroscopy of the nanoparticles surface reactions using both polarizations. The response of each polarization to streptavidin-biotin binding at the surface of gold nanoparticles is investigated in real time. Finally, using the principles of multimode spectroscopy, the nanoparticle's surface reactions are decoupled from the bulk solution refractive index variations. Schematic diagram of the NP-modified PWR sensor. PMID- 26871887 TI - Investigation of the Hydrogenation of 5-Methylfurfural by Noble Metal Nanoparticles in a Microcapillary Reactor. AB - On-column reaction gas chromatography (ocRGC) was successfully utilized as high throughput platform for monitoring of the conversion and selectivity of hydrogenation of 5-methylfurfural catalyzed by polymer-stabilized Ru and Pd nanoparticles. We were able to elucidate the effect of various reaction conditions, mainly together with the catalyst loading on the conversion rate and the selectivity of the reaction. Our strategy yields significant improvements in reaction analysis times and cost effectiveness in comparison to standard methods. We are able to demonstrate that ocRGC approach provides valuable information about the reaction system that gives scientists a tool to design suitable catalytic systems for enhanced sustainable chemistry in the future. PMID- 26871888 TI - The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold. AB - Today, chronic respiratory disease is one of the leading causes of mortality globally. Epithelial dysfunction can play a central role in its pathophysiology. The development of physiologically-representative in vitro model systems using tissue-engineered constructs might improve our understanding of epithelial tissue and disease. This study sought to engineer a bilayered collagen-hyaluronate (CHyA B) scaffold for the development of a physiologically-representative 3D in vitro tracheobronchial epithelial co-culture model. CHyA-B scaffolds were fabricated by integrating a thin film top-layer into a porous sub-layer with lyophilisation. The film layer firmly connected to the sub-layer with delamination occurring at stresses of 12-15 kPa. Crosslinked scaffolds had a compressive modulus of 1.9 kPa and mean pore diameters of 70 MUm and 80 MUm, depending on the freezing temperature. Histological analysis showed that the Calu-3 bronchial epithelial cell line attached and grew on CHyA-B with adoption of an epithelial monolayer on the film layer. Immunofluorescence and qRT-PCR studies demonstrated that the CHyA B scaffolds facilitated Calu-3 cell differentiation, with enhanced mucin expression, increased ciliation and the formation of intercellular tight junctions. Co-culture of Calu-3 cells with Wi38 lung fibroblasts was achieved on the scaffold to create a submucosal tissue analogue of the upper respiratory tract, validating CHyA-B as a platform to support co-culture and cellular organisation reminiscent of in vivo tissue architecture. In summary, this study has demonstrated that CHyA-B is a promising tool for the development of novel 3D tracheobronchial co-culture in vitro models with the potential to unravel new pathways in drug discovery and drug delivery. PMID- 26871889 TI - Ectopic bone formation in rapidly fabricated acellular injectable dense collagen Bioglass hybrid scaffolds via gel aspiration-ejection. AB - Gel aspiration-ejection (GAE) has recently been introduced as an effective technique for the rapid production of injectable dense collagen (IDC) gel scaffolds with tunable collagen fibrillar densities (CFDs) and microstructures. Herein, a GAE system was applied for the advanced production and delivery of IDC and IDC-Bioglass((r)) (IDC-BG) hybrid gel scaffolds for potential bone tissue engineering applications. The efficacy of GAE in generating mineralizable IDC-BG gels (from an initial 75-25 collagen-BG ratio) produced through needle gauge numbers 8G (3.4 mm diameter and 6 wt% CFD) and 14G (1.6 mm diameter and 14 wt% CFD) was investigated. Second harmonic generation (SHG) imaging of as-made gels revealed an increase in collagen fibril alignment with needle gauge number. In vitro mineralization of IDC-BG gels was confirmed where carbonated hydroxyapatite was detected as early as day 1 in simulated body fluid, which progressively increased up to day 14. In vivo mineralization of, and host response to, acellular IDC and IDC-BG gel scaffolds were further investigated following subcutaneous injection in adult rats. Mineralization, neovascularization and cell infiltration into the scaffolds was enhanced by the addition of BG and at day 21 post injection, there was evidence of remodelling of granulation tissue into woven bone-like tissue in IDC-BG. SHG imaging of explanted scaffolds indicated collagen fibril remodelling through cell infiltration and mineralization over time. In sum, the results suggest that IDC-BG hybrid gels have osteoinductive properties and potentially offer a novel therapeutic approach for procedures requiring the injectable delivery of a malleable and dynamic bone graft that mineralizes under physiological conditions. PMID- 26871890 TI - Antimicrobial peptide melimine coating for titanium and its in vivo antibacterial activity in rodent subcutaneous infection models. AB - Implant-associated infections represent a significant health problem and financial burden on healthcare systems. Current strategies for the treatment or prevention of such infections are still inadequate and new strategies are needed in this era of antibiotic resistance. Melimine, a synthetic antimicrobial peptide with broad spectrum activity against bacteria, fungi and protozoa, has been shown to be a promising candidate for development as antimicrobial coating for biomedical devices and implants. In this study, the in vitro and in vivo antimicrobial activity of melimine-coated titanium was tested. The titanium surface was amine-functionalised with 3-aminopropyltriethoxysilane (APTES) followed by reaction with a bifunctional linker 4-(N-maleimidomethyl)cyclohexane 1-carboxylic 3-sulfo-n-hydroxysuccinimide ester (Sulfo-SMCC) to yield a maleimide functionalised surface. Melimine was then tethered to the surface via a thioether linkage through a Michael addition reaction of the cysteine at its N-terminus with the maleimide moiety. Melimine coating significantly reduced in vitro adhesion and biofilm formation of Pseudomonas aeruginosa by up to 62% and Staphylococcus aureus by up to 84% on the titanium substrates compared to the blank (p < 0.05). The activity was maintained after ethylene oxide gas sterilisation. The coating was also challenged in both mouse and rat subcutaneous infection models and was able to reduce the bacterial load by up to 2 log10 compared to the uncoated surface (p < 0.05). Melimine coating is a promising candidate for development as a surface antimicrobial that can withstand industrial sterilisation while showing good biocompatibility. PMID- 26871891 TI - Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. AB - As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy. PMID- 26871892 TI - CE: Original Research: End-of-Life Care Behind Bars: A Systematic Review. AB - : To conduct a systematic review of the published research literature on end-of life (EOL) care in prisons in order to determine the current state of the science and suggest implications for nursing practice and areas for future research.Applying the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, we performed a comprehensive search of the literature using the following databases: CINAHL, Criminal Justice Abstracts, the National Criminal Justice Reference Service, PsycINFO, PubMed, and Sociological Abstracts. All databases were searched from the time of their inception through June 2014. All English-language articles that reported on original quantitative and qualitative research involving EOL or palliative care delivered to prisoners were included. We abstracted data, using the matrix method, and independently reviewed and graded the evidence on its level of strength and quality in accordance with the Johns Hopkins Nursing Evidence-Based Practice rating scales.Nineteen articles, all published between 2002 and 2014, met the inclusion criteria. Of these, 53% were published between 2009 and 2014, and 58% reported findings from qualitative research. One article reported on research conducted in the United Kingdom; the remaining 18 reported on research conducted in the United States. Capacity (that is, the number of prisoners requiring EOL care and the ability of the prison to accommodate them) and the site of EOL care delivery varied across studies, as did the criteria for admission to EOL or hospice services. Care was provided by prison health care staff, which variously included numerous professional disciplines, corrections officers, and inmate caregivers. The inmate caregivers, in particular, provided a wide array of services and were viewed positively by both EOL patients and health care staff. There are insufficient data to characterize the patients' and inmate caregivers' perceptions of the EOL care staff and the quality of care they provided. The screening criteria applied to inmate caregivers and the training they received varied widely among care programs. Inmates providing EOL care viewed caregiving as a transformational experience. Likewise, prison administrators and health care staff viewed inmate participation positively.This literature review reveals the challenges of providing EOL care to prisoners and may inspire nurses to consider steps they can take individually or within nursing organizations to improve this care and address the unique challenges faced by dying inmates. By being aware of these issues and advocating for best practices, nurses can help inmates at the end of life to have a dignified death. PMID- 26871893 TI - CE: Mental Health Matters: Revisiting Child Sexual Abuse and Survivor Issues. AB - Child sexual abuse is a global issue that nurses must be aware of and knowledgeable about as they care for children in various care settings. This article focuses on the prevalence, potential risk factors, and possible signs and symptoms of child sexual abuse. It also provides information about what nurses can do should they suspect that a child has been or is being abused. Because consequences can be far reaching and exist for many years after the abuse, this article also addresses the possible long-term issues faced by survivors and provides resources that nurses can share with patients. PMID- 26871894 TI - Meta-Analyses of Association Between BRAF(V600E) Mutation and Clinicopathological Features of Papillary Thyroid Carcinoma. AB - BACKGROUND/AIMS: The function of BRAF V600E as a prognostic biomarker continues controversial by reason of conflicting results in the published articles. METHODS: A systematical literature search for relevant articles was performed in PubMed, Cochrane Library, Google Scholar, Medline and Embase updated to August 5, 2015. The Chi-square test and I2 were employed to examine statistical heterogeneity. Pooled ORs with their corresponding 95% confidence intervals (95%CIs) were calculated to assess the relationship between clinicopathological features and BRAF(V600E) mutation. Subgroup analyses by ethnicity were also performed to explore the potential sources of heterogeneity. Furthermore, publication bias was detected using the funnel plot and all statistical analyses were conducted by the software of R 3.12. RESULTS: Of 25,241 cases with PTC, 15,290 (60.6%) were positive for BRAF mutation and 9,951 (39.4%) were tested negative for BRAF mutation. Negative status of BRAF(V600E) mutation negative was significantly associated with gender (OR = 0.90, 95%CI = 0.83-0.97) and concomitant hashimoto thyroiditis (OR = 0.53, 95%CI = 0.43-0.64). By contrast, positive status of BRAF(V600E) mutation was a significant predictor of multifocality (OR = 1.23; 95%CI = 1.14-1.32), extrathyroidal extension (OR = 2.23; 95%CI = 1.90-2.63), TNM stage (OR = 1.67; 95%CI = 1.53-1.81), lymph node metastasis (OR = 1.67; 95%CI = 1.45-1.93), vascular invasion (OR = 1.47; 95%CI = 1.22-1.79) and recurrence/persistence (OR = 2.33; 95%CI = 1.71-3.18). However, there was no significant association between BRAF(V600E) mutation and factors including age > 45 (OR = 0.98; 95%CI = 0.89-1.07), tumor size (OR = 0.84; 95%CI = 0.64-1.09) and distant metastasis (OR = 1.23; 95%CI = 0.67-2.27). CONCLUSION: This meta-analysis confirmed significant associations between BRAF(V600E) mutation and female gender, multifocality, ETE, LNM, TNM stage, concomitant hashimoto thyroiditis, vascular invasion and recurrence/persistence, suggesting the predictive value of BRAF(V600E) mutation for PTC prognosis. PMID- 26871895 TI - A Brief Review of the Link between Environment and Male Reproductive Health: Lessons from Studies of Testicular Germ Cell Cancer. AB - During the past few decades there has been a significantly increasing trend in germ cell tumours all over the world, particularly in countries with Caucasian populations. The changes in incidence have occurred so fast that only environmental factors can explain this development. This review focuses on the hypothesis that testicular germ cell cancer, which originates from germ cell neoplasia in situ, is of foetal origin and associated with other male reproductive problems through a testicular dysgenesis syndrome, also including foetal origin of impaired spermatogenesis, hypospadias and cryptorchidism. There is little doubt that environmental factors associated with modern lifestyles have - in a broad sense - had an adverse influence on male reproductive health. The hypothesis that exposure to endocrine-disrupting chemicals plays a fundamental role in this trend is plausible. This is based on evidence from animal studies that demonstrate adverse reproductive effects caused by a number of endocrine disrupting chemicals to which humans are exposed as part of our modern lifestyle. PMID- 26871896 TI - Optical Intensities of Different Compartments of Subretinal Fluid in Acute Vogt Koyanagi-Harada Disease. AB - PURPOSE: To investigate the optical intensity in different compartments of subretinal fluid in acute Vogt-Koyanagi-Harada (VKH) disease by using spectral domain optical coherence tomography (SD-OCT). METHODS: Fifty acute VKH eyes and 25 cases with acute central serous chorioretinopathy (CSCR) were included in this retrospective comparative study. The optical intensities of subretinal fluid, vitreous humour and the entire scanned region displayed by SD-OCT were measured with Image J by three independent readers. In the VKH eyes with subretinal septa, the subretinal fluid was segmented into two types of compartments, supra-septa space and sub-septa space. Optical intensity ratios of different compartments of subretinal fluids divided by vitreous humour or the entire scanned region were compared. RESULTS: The measurement of optical intensity was highly reproducible (intraclass correlation coefficient> 0.9). The optical intensity of the supra septa space divided by the vitreous humour was significantly higher compared to that of sub-septa space in VKH (mean difference = 4.27 +/- 5.15, p <0.001). The optical intensity ratio of the supra-septa space (1.14 +/- 0.12), but not subsepta space (1.05 +/- 0.05) in VKH, was significantly higher compared to that of the subretinal space in VKH without the subretinal septa (1.07 +/- 0.08), and the subretinal fluid in CSCR (1.08 +/- 0.09). Similar results were found for the optical intensity ratios divided by the entire scan region. CONCLUSION: The optical intensity in the supra-septa space of VKH is higher compared to the sub septa space in VKH, subretinal space in VKH and CSCR, suggesting that the components in these spaces are different. PMID- 26871897 TI - Physiological Contribution in Spontaneous Oscillations: An Approximate Quality Assurance Index for Resting-State fMRI Signals. AB - Resting-state fMRI (rs-fMRI) is receiving substantial attention for its sensitivity to functional abnormality in the brain networks of people with psychiatric and neurological disorders. However, because of the variety of rs fMRI processing methods, the necessity of rs-fMRI quality assurance is increasing. Conventionally, the temporal signal-to-noise ratio (tSNR) is generally adopted for quality examination, but the tSNR does not guarantee reliable functional connectivity (FC) outcomes. Theoretically, intrinsic FC is supposed to reflect the spontaneous synchronization of neuronal basis, rather than that from thermal noise or non-neuronal physiological noise. Therefore, we proposed a new quality-assurance index for rs-fMRI to estimate the physiological contributions in spontaneous oscillations (PICSO). The PICSO index was designed as a voxel-wise measure for facilitating practical applications to all existing rs-fMRI data sets on the basis of two assumptions: Gaussian distributions in temporal fluctuations and ultra-slow changes of neural-based physiological fluctuations. To thoroughly validate the sensitivity of the proposed PICSO index to FC, we calibrated the preprocessing steps according to phantom data and verified the relationship between the PICSO and factors that are considered to affect FC in healthy participants (n = 12). Our results demonstrated that FC showed a significantly positive correlation with the PICSO. Moreover, for generating robust FC outcomes, directly acquiring data at a relatively large voxel size was more effective than performing smoothness on high-resolution data sets. In conclusion, compared with tSNR, the PICSO index is more sensitive to the resulting FC, providing a practical quality-assurance indicator for all existing rs-fMRI data sets. PMID- 26871900 TI - Management of primary malignant lymphoma of the parotid gland in a series of seven hundred and forty-five patients. PMID- 26871898 TI - Control of Trachoma from Achham District, Nepal: A Cross-Sectional Study from the Nepal National Trachoma Program. AB - BACKGROUND: The WHO seeks to control trachoma as a public health problem in endemic areas. Achham District in western Nepal was found to have TF (trachoma follicular) above 20% in a 2006 government survey, triggering 3 annual mass drug administrations finishing in 2010. Here we assess the level of control that has been achieved using surveillance for clinical disease, ocular chlamydia trachomatis infection, and serology for antibodies against chlamydia trachomatis protein antigens. METHODS: We conducted a cross-sectional survey of children aged 1-9 years in communities in Achham District in early 2014 including clinical examination validated with photographs, conjunctival samples for Chlamydia trachomatis (Amplicor PCR), and serological testing for antibodies against chlamydia trachomatis protein antigens pgp3 and CT694 using the Luminex platform. FINDINGS: In 24 randomly selected communities, the prevalence of trachoma (TF and/or TI) in 1-9 year olds was 3/1124 (0.3%, 95% CI 0.1 to 0.8%), and the prevalence of ocular chlamydia trachomatis infection was 0/1124 (0%, 95% CI 0 to 0.3%). In 18 communities selected because they had the highest prevalence of trachoma in a previous survey, the prevalence of TF and/or TI was 7/716 (1.0%, 95% CI 0.4 to 2.0%) and the prevalence of ocular chlamydia trachomatis infection was 0/716 (0%, 95% CI 0 to 0.5%). In 3 communities selected for serological testing, the prevalence of trachoma was 0/68 (0%, 95% CI 0 to 5.3%), the prevalence of ocular chlamydia trachomatis infection was 0/68 (0%, 95% CI 0 to 0.5%), the prevalence of antibodies against chlamydia trachomatis protein antigen pgp3 was 1/68 (1.5%, 95% CI 0.04% to 7.9%), and the prevalence of antibodies against chlamydia trachomatis protein antigen CT694 was 0/68 (0%, 95% CI 0 to 5.3%). CONCLUSION/SIGNIFICANCE: This previously highly endemic district in Nepal has little evidence of recent clinical disease, chlamydia trachomatis infection, or serological evidence of trachoma, suggesting that epidemiological control has been achieved. PMID- 26871899 TI - Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review. AB - Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity. PMID- 26871901 TI - Positive Selection or Free to Vary? Assessing the Functional Significance of Sequence Change Using Molecular Dynamics. AB - Evolutionary arms races between pathogens and their hosts may be manifested as selection for rapid evolutionary change of key genes, and are sometimes detectable through sequence-level analyses. In the case of protein-coding genes, such analyses frequently predict that specific codons are under positive selection. However, detecting positive selection can be non-trivial, and false positive predictions are a common concern in such analyses. It is therefore helpful to place such predictions within a structural and functional context. Here, we focus on the p19 protein from tombusviruses. P19 is a homodimer that sequesters siRNAs, thereby preventing the host RNAi machinery from shutting down viral infection. Sequence analysis of the p19 gene is complicated by the fact that it is constrained at the sequence level by overprinting of a viral movement protein gene. Using homology modeling, in silico mutation and molecular dynamics simulations, we assess how non-synonymous changes to two residues involved in forming the dimer interface-one invariant, and one predicted to be under positive selection-impact molecular function. Interestingly, we find that both observed variation and potential variation (where a non-synonymous change to p19 would be synonymous for the overprinted movement protein) does not significantly impact protein structure or RNA binding. Consequently, while several methods identify residues at the dimer interface as being under positive selection, MD results suggest they are functionally indistinguishable from a site that is free to vary. Our analyses serve as a caveat to using sequence-level analyses in isolation to detect and assess positive selection, and emphasize the importance of also accounting for how non-synonymous changes impact structure and function. PMID- 26871902 TI - Approaches to Foster Transfer of Formal Principles: Which Route to Take? AB - Enabling learners to transfer knowledge about formal principles to new problems is a major aim of science and mathematics education, which, however, is notoriously difficult to reach. Previous research advocates different approaches of how to introduce principles to foster the transfer of knowledge about formal principles. One approach suggests teaching a generic formalism of the principles. Another approach suggests presenting (at least) two concrete cases instantiating the principle. A third approach suggests presenting a generic formalism accompanied by a case. As yet, though, empirical results regarding the transfer potential of these approaches are mixed and difficult to integrate as the three approaches have rarely been tested competitively. Furthermore, the approaches have been evaluated in relation to different control conditions, and they have been assessed using varying transfer measures. In the present experiment, we introduced undergraduates to the formal principles of propositional logic with the aim to systematically compare the transfer potential of the different approaches in relation to each other and to a common control condition by using various learning and transfer tasks. Results indicate that all approaches supported successful learning and transfer of the principles, but also caused systematic differences in the magnitude of transfer. Results indicate that the combination of a generic formalism with a case was surprisingly unsuccessful while learners who compared two cases outperformed the control condition. We discuss how the simultaneous assessment of the different approaches allows to more precisely capture the underlying learning mechanisms and to advance theory on how these mechanisms contribute to transfer performance. PMID- 26871904 TI - Preeclampsia and Future Risk for Maternal Ophthalmic Complications. AB - Objective To investigate whether patients with a history of preeclampsia have an increased risk of long-term ophthalmic complications. Study Design A population based study comparing the incidence of long-term maternal ophthalmic complications in a cohort of women with and without a history of preeclampsia. Results During the study period, a total of 103,183 deliveries met the inclusion criteria; 8.1% (n = 8,324) occurred in patients with a diagnosis of preeclampsia during at least one of their pregnancies. Patients with preeclampsia had a significantly higher incidence of long-term ophthalmic morbidity such as diabetic retinopathy and retinal detachment. In addition, a positive linear correlation was found between the severity of preeclampsia and the prevalence of future ophthalmic morbidities (0.3 vs. 0.5 vs. 2.2%, respectively). Kaplan-Meier survival curve indicated that women with preeclampsia had higher rates of total ophthalmic morbidity (0.2 vs. 0.4%, for no preeclampsia and with preeclampsia, respectively; odds ratio = 2.06, 95% confidence interval: 1.42-2.99; p < 0.001). In a Cox proportional hazards model, adjusted for confounders, a history of preeclampsia remained independently associated with ophthalmic complications. Conclusion Preeclampsia is an independent risk factor for long-term maternal ophthalmic morbidity, specifically diabetic retinopathy and retinal detachment. This risk is more substantial depending on the severity of the disease. PMID- 26871903 TI - Integration of Stem Cell to Chondrocyte-Derived Cartilage Matrix in Healthy and Osteoarthritic States in the Presence of Hydroxyapatite Nanoparticles. AB - We investigated the effectiveness of integrating tissue engineered cartilage derived from human bone marrow derived stem cells (HBMSCs) to healthy as well as osteoarthritic cartilage mimics using hydroxyapatite (HA) nanoparticles immersed within a hydrogel substrate. Healthy and diseased engineered cartilage from human chondrocytes (cultured in agar gels) were integrated with human bone marrow stem cell (HBMSC)-derived cartilaginous engineered matrix with and without HA, and evaluated after 28 days of growth. HBMSCs were seeded within photopolymerizable poly (ethylene glycol) diacrylate (PEGDA) hydrogels. In addition, we also conducted a preliminary in vivo evaluation of cartilage repair in rabbit knee chondral defects treated with subchondral bone microfracture and cell-free PEGDA with and without HA. Under in vitro conditions, the interfacial shear strength between tissue engineered cartilage derived from HBMSCs and osteoarthritic chondrocytes was significantly higher (p < 0.05) when HA nanoparticles were incorporated within the HBMSC culture system. Histological evidence confirmed a distinct spatial transition zone, rich in calcium phosphate deposits. Assessment of explanted rabbit knees by histology demonstrated that cellularity within the repair tissues that had filled the defects were of significantly higher number (p < 0.05) when HA was used. HA nanoparticles play an important role in treating chondral defects when osteoarthritis is a co-morbidity. We speculate that the calcified layer formation at the interface in the osteoarthritic environment in the presence of HA is likely to have attributed to higher interfacial strength found in vitro. From an in vivo standpoint, the presence of HA promoted cellularity in the tissues that subsequently filled the chondral defects. This higher presence of cells can be considered important in the context of accelerating long-term cartilage remodeling. We conclude that HA nanoparticles play an important role in engineered to native cartilage integration and cellular processes. PMID- 26871905 TI - Randomized, Double-Blinded Trial of Magnesium Sulfate Tocolysis versus Intravenous Normal Saline for Preterm Nonsevere Placental Abruption. AB - Objective To evaluate the efficacy and safety of magnesium sulfate in the resolution of vaginal bleeding and contractions in nonsevere placental abruption. Study Design Thirty women between 24 and 34 weeks of gestation diagnosed with nonsevere placental abruption were randomized to receive magnesium sulfate tocolysis or normal saline infusion. The primary outcome was the proportion of women undelivered at 48 hours with resolution of vaginal bleeding and uterine contractions. Maternal and neonatal outcomes were also compared. Results Fifteen (50%) women received magnesium sulfate tocolysis and 15 (50%) received intravenous saline. There was no difference in the number of women who were undelivered at 48 hours with resolution of vaginal bleeding and contractions in the magnesium sulfate (80.0%) and saline (66.7%; p-value = 0.68) groups. There were no differences between groups in the gestational age at randomization, time to uterine quiescence, time on study drug, length of hospitalization, days from randomization to delivery, incidence of side effects, or admissions to the neonatal intensive care unit. Conclusions Magnesium sulfate tocolysis did not provide a significant difference in pregnancy prolongation in the management of preterm nonsevere placental abruption. Recruitment goals were not met due to the introduction of the use of magnesium sulfate for neuroprotection. PMID- 26871906 TI - Easy as ABC: A System to Stratify Category II Fetal Heart Rate Tracings. AB - Objective To evaluate whether a subcategory system for category II tracings can improve team communication and perinatal outcomes. Study Design We collected data prospectively for 15 months, first using the NICHD system, followed by the ABC system, which divides category II tracings into subcategories A, B, and C, each representing increased risk for metabolic acidemia. We surveyed providers about communication effectiveness and agreement on tracing interpretation for each system. In cases where the communication system was used to alert an off-site physician about a category II tracing, we compared arrival to L&D and NICU admissions. Results The ABC system was preferred (69%, n = 152) and considered a more effective tool for communicating concerning fetal status (80% vs. 43%, p < 0.01). Participants also reported greater agreement on tracing interpretation (79% for ABC vs. 64% for NICHD, p = 0.046). When an off-site physician was contacted about a category II tracing (n = 95), they were more likely to arrive to L&D (44% vs. 20%, p < 0.01) and have fewer NICU admissions (0% vs. 6%, p < 0.01) with the ABC system. Conclusion The ABC system resulted in improved team communication, increased physician response, and decreased NICU admissions. Using standardized communication may offer a useful strategy for identifying and expediting care. PMID- 26871907 TI - miRNA Repertoires of Demosponges Stylissa carteri and Xestospongia testudinaria. AB - MicroRNAs (miRNAs) are small regulatory RNAs that are involved in many biological process in eukaryotes. They play a crucial role in modulating genetic expression of their targets, which makes them integral components of transcriptional regulatory networks. As sponges (phylum Porifera) are commonly considered the most basal metazoan, the in-depth capture of miRNAs from these organisms provides additional clues to the evolution of miRNA families in metazoans. Here, we identified the core proteins involved in the biogenesis of miRNAs, and obtained evidence for bona fide miRNA sequences for two marine sponges Stylissa carteri and Xestospongia testudinaria (11 and 19 respectively). Our analysis identified several miRNAs that are conserved amongst demosponges, and revealed that all of the novel miRNAs identified in these two species are specific to the class Demospongiae. PMID- 26871908 TI - Comparison of the Combined versus Conventional Apgar Scores in Predicting Adverse Neonatal Outcomes. AB - OBJECTIVES: Assessing the value of the Combined-Apgar score in predicting neonatal mortality and morbidity compared to the Conventional-Apgar. METHODS: This prospective cohort study evaluated 942 neonates (166 very preterm, 233 near term, and 543 term) admitted to a tertiary referral hospital. At 1- and 5-minutes after delivery, the Conventional and Combined Apgar scores were recorded. The neonates were followed, and the following information was recorded: the occurrence of severe hyperbilirubinemia requiring medical intervention, the requirement for mechanical ventilation, the occurrence of intraventricular hemorrhage (IVH), and neonatal mortality. RESULTS: Before adjusting for the potential confounders, a low Conventional (<7) or Combined (<10) Apgar score at 5 minutes was associated with adverse neonatal outcomes. However, after adjustment for the gestational age, birth weight and the requirement for neonatal resuscitation in the delivery room, a depressed 5-minute Conventional-Apgar score lost its significant associations with all the measured adverse outcomes; after the adjustments, a low 5-minute Combined-Apgar score remained significantly associated with the requirement for mechanical ventilation (OR,18.61; 95%CI,6.75 51.29), IVH (OR,4.8; 95%CI,1.91-12.01), and neonatal mortality (OR,20.22; 95%CI,4.22-96.88). Additionally, using Receiver Operating Characteristics (ROC) curves, the area under the curve was higher for the Combined-Apgar than the Conventional-Apgar for the prediction of neonatal mortality and the measured morbidities among all the admitted neonates and their gestational age subgroups. CONCLUSIONS: The newly proposed Combined-Apgar score can be a good predictor of neonatal mortality and morbidity in the admitted neonates, regardless of their gestational age and resuscitation status. It is also superior to the Conventional Apgar in predicting adverse neonatal outcomes in very preterm, near term and term neonates. PMID- 26871909 TI - Trajectories of Pain and Function after Primary Hip and Knee Arthroplasty: The ADAPT Cohort Study. AB - BACKGROUND AND PURPOSE: Pain and function improve dramatically in the first three months after hip and knee arthroplasty but the trajectory after three months is less well described. It is also unclear how pre-operative pain and function influence short- and long-term recovery. We explored the trajectory of change in function and pain until and beyond 3-months post-operatively and the influence of pre-operative self-reported symptoms. METHODS: The study was a prospective cohort study of 164 patients undergoing primary hip (n = 80) or knee (n = 84) arthroplasty in the United Kingdom. Self-reported measures of pain and function using the Western Ontario and McMaster Universities Osteoarthritis index were collected pre-operatively and at 3 and 12 months post-operatively. Hip and knee arthroplasties were analysed separately, and patients were split into two groups: those with high or low symptoms pre-operatively. Multilevel regression models were used for each outcome (pain and function), and the trajectories of change were charted (0-3 months and 3-12 months). RESULTS: Hip: Most improvement occurred within the first 3 months following hip surgery and patients with worse pre-operative scores had greater changes. The mean changes observed between 3 and twelve months were statistically insignificant. One year after surgery, patients with worse pre-operative scores had post-operative outcomes similar to those observed among patients with less severe pre-operative symptoms. Knee: Most improvement occurred in the first 3 months following knee surgery with no significant change thereafter. Despite greater mean change during the first three months, patients with worse pre-operative scores had not 'caught-up' with those with less severe pre-operative symptoms 12 months after their surgery. CONCLUSION: Most symptomatic improvement occurred within the first 3 months after surgery with no significant change between 3-12 months. Further investigations are now required to determine if patients with severe symptoms at the time of their knee arthroplasty have a different pre-surgical history than those with less severe symptoms and if they could benefit from earlier surgical intervention and tailored rehabilitation to achieve better post-operative patient-reported outcomes. PMID- 26871910 TI - Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host. AB - African trypanosomes thrive in the bloodstream and tissue spaces of a wide range of mammalian hosts. Infections of cattle cause an enormous socio-economic burden in sub-Saharan Africa. A hallmark of the trypanosome lifestyle is the flagellate's incessant motion. This work details the cell motility behavior of the four livestock-parasites Trypanosoma vivax, T. brucei, T. evansi and T. congolense. The trypanosomes feature distinct swimming patterns, speeds and flagellar wave frequencies, although the basic mechanism of flagellar propulsion is conserved, as is shown by extended single flagellar beat analyses. Three dimensional analyses of the trypanosomes expose a high degree of dynamic pleomorphism, typified by the 'cellular waveform'. This is a product of the flagellar oscillation, the chirality of the flagellum attachment and the stiffness of the trypanosome cell body. The waveforms are characteristic for each trypanosome species and are influenced by changes of the microenvironment, such as differences in viscosity and the presence of confining obstacles. The distinct cellular waveforms may be reflective of the actual anatomical niches the parasites populate within their mammalian host. T. vivax displays waveforms optimally aligned to the topology of the bloodstream, while the two subspecies T. brucei and T. evansi feature distinct cellular waveforms, both additionally adapted to motion in more confined environments such as tissue spaces. T. congolense reveals a small and stiff waveform, which makes these parasites weak swimmers and destined for cell adherence in low flow areas of the circulation. Thus, our experiments show that the differential dissemination and annidation of trypanosomes in their mammalian hosts may depend on the distinct swimming capabilities of the parasites. PMID- 26871912 TI - Looking back, looking forward: Recovery journeys in a high secure hospital. AB - A qualitative study of staff and service users' views of recovery was undertaken in a UK high secure hospital working to implement recovery practices. 30 staff and 25 service users participated in semi-structured interviews or focus groups. Thematic analysis identified four broad accounts of how recovery was made sense of in the high secure environment: the importance of meaningful occupation; valuing relationships; recovery journeys and dialogue with the past; and recovery as personal responsibility. These themes are discussed with an emphasis on service user strategies of cooperation or resistance, respectively advancing or impeding progress through the system. In this context the notion of cooperation is, for many, commensurate with compliance with a dominant medical model. The policy framing of recovery opens up contemplation of treatment alternatives, more participatory approaches to risk management, and emphasise the value of relational skills, but may not elude the overarching bio-psychiatric episteme. PMID- 26871911 TI - Structural and Functional Characterization of a Caenorhabditis elegans Genetic Interaction Network within Pathways. AB - A genetic interaction (GI) is defined when the mutation of one gene modifies the phenotypic expression associated with the mutation of a second gene. Genome-wide efforts to map GIs in yeast revealed structural and functional properties of a GI network. This provided insights into the mechanisms underlying the robustness of yeast to genetic and environmental insults, and also into the link existing between genotype and phenotype. While a significant conservation of GIs and GI network structure has been reported between distant yeast species, such a conservation is not clear between unicellular and multicellular organisms. Structural and functional characterization of a GI network in these latter organisms is consequently of high interest. In this study, we present an in-depth characterization of ~1.5K GIs in the nematode Caenorhabditis elegans. We identify and characterize six distinct classes of GIs by examining a wide-range of structural and functional properties of genes and network, including co expression, phenotypical manifestations, relationship with protein-protein interaction dense subnetworks (PDS) and pathways, molecular and biological functions, gene essentiality and pleiotropy. Our study shows that GI classes link genes within pathways and display distinctive properties, specifically towards PDS. It suggests a model in which pathways are composed of PDS-centric and PDS independent GIs coordinating molecular machines through two specific classes of GIs involving pleiotropic and non-pleiotropic connectors. Our study provides the first in-depth characterization of a GI network within pathways of a multicellular organism. It also suggests a model to understand better how GIs control system robustness and evolution. PMID- 26871913 TI - Time for a patient-oriented outcome in vitiligo: the vitiligo noticeability scale. PMID- 26871914 TI - Rare inherited skin diseases and the Genomics England 100 000 Genome Project. PMID- 26871915 TI - A biosimilarity index for psoriasis. PMID- 26871916 TI - Treating actinic keratosis. PMID- 26871917 TI - Prediction of high total naevus count to estimate melanoma risk. We need more, don't we? PMID- 26871918 TI - CARD14 alterations and psoriasis: are psoriasis and related disorders genetic autoinflammatory diseases? PMID- 26871919 TI - Hand dermatitis in construction workers: a lesson in genetic epidemiology. PMID- 26871920 TI - A possible mechanism of hypercoagulation status in scleroderma. PMID- 26871921 TI - Labelling: do we have it right? PMID- 26871922 TI - Kidney disease in moderate-to-severe psoriasis: a critical appraisal. AB - AIM: Using a population-based cohort, Wan et al. examined the risk of moderate-to advanced (stage 3-5) chronic kidney disease (CKD) in patients with psoriasis. SETTING AND DESIGN: A population-based cohort was constructed using The Health Improvement Network (THIN) database. THIN is an electronic primary healthcare records database containing routinely collected medical diagnosis and drug prescribing data on > 9 million patients in the U.K. Data were collected prospectively on 143 883 adults (aged 18-90 years) with psoriasis. Of these, 7354 had severe psoriasis, as defined by prescription codes for systemic medication or treatment codes for phototherapy. Patients with psoriasis were matched with up to five nonpsoriasis age- and practice-matched controls. Patients with a diagnosis of CKD before study entry were excluded. In addition, baseline data from the Incident Health Outcomes and Psoriasis Events (iHOPE) study, a cohort of 8731 primary care patients aged 25-64 years with psoriasis, was included. Psoriasis severity was categorized according to body surface area (BSA) involvement as estimated by general practitioners. A similar method using a patient-reported BSA assessment tool was previously validated by the same group. Patients were matched by age and practice with 10 nonpsoriasis controls. STUDY EXPOSURE: Psoriasis, identified on the basis of a recorded diagnostic code for psoriasis. OUTCOMES: Incident CKD was defined as the presence of a recorded diagnostic code consistent with moderate-to-advanced (stage 3-5) CKD or laboratory parameters consistent with the diagnosis (estimated glomerular filtration rate < 60 mL min(-1) 1.73 m( 2) ) during follow-up. Prevalent CKD (as defined above) in the cross-sectional data from the iHOPE study. RESULTS: The adjusted hazard ratios for incident CKD were 1.05 [95% confidence interval (CI) 1.02-1.07], 0.99 (95% CI 0.97-1.02) and 1.93 (95% CI 1.79-2.08) in the overall, mild and severe psoriasis groups, respectively. In the nested cross-sectional study (iHOPE) the adjusted prevalence odds ratios for CKD were 0.89 (95% CI 0.72-1.10), 1.36 (95% CI 1.06-1.74) and 1.58 (95% CI 1.07-2.34) in the mild, moderate and severe psoriasis groups, respectively. CONCLUSIONS: Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced CKD, independently of traditional risk factors. PMID- 26871923 TI - Response to 'Kidney disease in moderate-to-severe psoriasis: a critical appraisal'. PMID- 26871924 TI - Kidney disease in moderate-to-severe psoriasis: commentary. PMID- 26871926 TI - Cover Image: Music box spines. PMID- 26871925 TI - Heritability of naevus patterns in an adult twin cohort from the Brisbane Twin Registry: a cross-sectional study. AB - BACKGROUND: Heritability of naevi counts is widely acknowledged as a potential surveillance parameter for prevention purposes. The contribution of heritability to the changes seen in naevus number and morphology over time and their corresponding dermoscopic characteristics is unknown, but is important to understand in order to account for adequate prevention measures. OBJECTIVES: To identify naevus characteristics that are strongly influenced by heritability. METHODS: This cross-sectional study included 220 individuals [76 monozygotic (MZ), 144 dizygotic (DZ)], recruited from the Brisbane Twin Naevus Study. Participants received full body imaging and dermoscopy of naevi >= 5 mm in diameter. Dermoscopic type, total naevus count (TNC), change in TNC with age, and naevus distribution, size, colour and profile were compared between MZ and DZ twins. Heritability of these traits was assessed via Falconer's estimate. RESULTS: Significant differences were found in comparing MZ and DZ twins for TNC, numbers of naevi 5.0-7.9 mm in diameter, counts of light-brown naevi, naevi on the back and sun-protected sites, and naevi with the 'nonspecific' dermoscopic pattern. CONCLUSIONS: This study strongly supports a heritable component to TNC, as well as changes in TNC, and the number of medium-sized naevi, light-brown naevi, specific sites and certain dermoscopic features in adults. These characteristics should be taken into account by naevus surveillance programmes and further studied to identify candidate gene associations for clinical and dermoscopic patterns in conjunction with melanoma risk stratification. PMID- 26871928 TI - Plain language summaries. PMID- 26871930 TI - European Lampreys: New Insights on Postglacial Colonization, Gene Flow and Speciation. AB - Ice ages are known to be the most dominant palaeoclimatic feature occurring on Earth, producing severe climatic oscillations and consequently shaping the distribution and the population structure of several species. Lampreys constitute excellent models to study the colonization of freshwater systems, as they commonly appear in pairs of closely related species of anadromous versus freshwater resident adults, thus having the ability to colonize new habitats, through the anadromous species, and establish freshwater resident derivates. We used 10 microsatellite loci to investigate the spatial structure, patterns of gene flow and migration routes of Lampetra populations in Europe. We sampled 11 populations including the migratory L. fluviatilis and four resident species, L. planeri, L. alavariensis, L. auremensis and L. lusitanica, the last three endemic to the Iberian Peninsula. In this southern glacial refugium almost all sampled populations represent a distinct genetic cluster, showing high levels of allopatric differentiation, reflecting long periods of isolation. As result of their more recent common ancestor, populations from northern Europe are less divergent among them, they are represented by fewer genetic clusters, and there is evidence of strong recent gene flow among populations. These previously glaciated areas from northern Europe may have been colonized from lampreys expanding out of the Iberian refugia. The pair L. fluviatilis/L. planeri is apparently at different stages of speciation in different locations, showing evidences of high reproductive isolation in the southern refugium, and low differentiation in the north. PMID- 26871931 TI - Correction: Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography. PMID- 26871933 TI - Occupational allergy to pharmaceutical products. AB - PURPOSE OF REVIEW: Occupational allergy in healthcare workers is common and can lead to significant costs from both loss of productivity within the workforce as well as those associated with diagnosis and treatment. This review aims to provide an update on drugs implicated in causing occupational allergy. RECENT FINDINGS: Drugs traditionally reported as causing occupational allergy, such as penicillin, remain problematic. However, as their use reduces and newer drugs, such as cephalosporins, are used more frequently there is a changing pattern to occupational sensitization. In some studies up to 17% of healthcare workers now appear sensitized to cephalosporins. Other drug classes also reported include proton pump inhibitors and benzodiazepines. Interestingly, drugs such as omeprazole and tetrazepam rarely cause allergy in patients but can be very sensitizing if applied topically or inhaled. Recent studies involving pharmaceutical company employees show that this problem can no longer be considered primarily related to healthcare workers. SUMMARY: The diagnosis of occupational allergy to drugs can be complicated and has been shown to take up to 5 years from the onset of symptoms. Ultimately, workplace avoidance remains key; however, an up to date awareness of culprit drugs and the patterns of allergy seen are key to a prompt resolution of symptoms. PMID- 26871932 TI - Predicting Where a Radiation Will Occur: Acoustic and Molecular Surveys Reveal Overlooked Diversity in Indian Ocean Island Crickets (Mogoplistinae: Ornebius). AB - Recent theory suggests that the geographic location of island radiations (local accumulation of species diversity due to cladogenesis) can be predicted based on island area and isolation. Crickets are a suitable group for testing these predictions, as they show both the ability to reach some of the most isolated islands in the world, and to speciate at small spatial scales. Despite substantial song variation between closely related species in many island cricket lineages worldwide, to date this characteristic has not received attention in the western Indian Ocean islands; existing species descriptions are based on morphology alone. Here we use a combination of acoustics and DNA sequencing to survey these islands for Ornebius crickets. We uncover a small but previously unknown radiation in the Mascarenes, constituting a three-fold increase in the Ornebius species diversity of this archipelago (from two to six species). A further new species is detected in the Comoros. Although double archipelago colonisation is the best explanation for species diversity in the Seychelles, in situ cladogenesis is the best explanation for the six species in the Mascarenes and two species of the Comoros. Whether the radiation of Mascarene Ornebius results from intra- or purely inter- island speciation cannot be determined on the basis of the phylogenetic data alone. However, the existence of genetic, song and ecological divergence at the intra-island scale is suggestive of an intra island speciation scenario in which ecological and mating traits diverge hand-in hand. Our results suggest that the geographic location of Ornebius radiations is partially but not fully explained by island area and isolation. A notable anomaly is Madagascar, where our surveys are consistent with existing accounts in finding no Ornebius species present. Possible explanations are discussed, invoking ecological differences between species and differences in environmental history between islands. PMID- 26871934 TI - Scaffold Hopping Approach to a New Series of Pyridine Derivatives as Potent Inhibitors of CDK2. AB - A scaffold hopping approach was exploited to guide the discovery of a series of pyridine derivatives as novel cyclin-dependent kinase (CDK2) inhibitors. These new compounds were designed, synthesized, and evaluated as CDK2 inhibitors. Most of the compounds showed potent inhibition against CDK2, and preliminary structure activity relationship trends were revealed. A docking study on the most potent compound 6g implied the structural basis for potent CDK2 inhibition. All of the synthesized compounds were also evaluated for their cytotoxicity against the H522 and U87 cancer cell lines. The most potent and drug-like compound 6g was further tested against a normal cell line (L02), demonstrating that this compound is selectively toxic toward cancer cell lines. The results provide the foundation for further improving the potency of this series of compounds. PMID- 26871935 TI - Treatment of colon cancer with oncolytic herpes simplex virus in preclinical models. AB - Cancer stem cells (CSCs), which are a rare population in any type of cancer, including colon cancer, are tumorigenic and responsible for cancer recurrence and metastasis. CSCs have been isolated from a number of different solid tumors recently, although the isolation of CSCs in colon cancer is still challenging. We cultured colon cancer cells in stem cell medium to obtain colonosphere cells. These cells possessed the characteristics of CSCs, with a high capacity of tumorigenicity, migration and invasion in vitro and in vivo. The isolation and identification of CSCs have provided new targets for the therapeutics. Oncolytic herpes simplex viruses (oHSV) are an effective strategy for killing colon cancer cells in preclinical models. Here, we examined the efficacy of an oncolytic herpes simplex virus type 2 (oHSV2) in killing colon cancer cells and colon cancer stem-like cells (CSLCs). oHSV2 was found to be highly cytotoxic to the adherent and sphere cells in vitro, and oHSV2 treatment in vivo significantly inhibited tumor growth. This study demonstrates that oHSV2 is effective against colon cancer cells and colon CSLCs and could be a promising strategy for treating colon cancer patients. PMID- 26871936 TI - Prevalence and Patterns of Multi-Morbidity in Serbian Adults: A Cross-Sectional Study. AB - INTRODUCTION: Like many developing countries, Serbia is facing a growing burden of chronic diseases. Within such public health issue, multi-morbidity requires a special attention. AIMS: This study investigated the prevalence of multi morbidity in the Serbia population and assessed the co-occurrence of chronic diseases by age and gender. METHODS: We analyzed data from the 2013 National Health Survey, which included 13,103 individuals >= 20 years old. Multi-morbidity patterns were identified by exploratory factor analysis of data on self-reported chronic diseases, as well as data on measured body weight and height. The analysis was stratified by age and gender. RESULTS: Multi-morbidity was present in nearly one-third of respondents (26.9%) and existed in all age groups, with the highest prevalence among individuals aged 65 years and older (47.2% of men and 65.0% of women). Six patterns of multi-morbidity were identified: non communicable, cardio-metabolic, respiratory, cardiovascular, aggregate, and mechanical/mental/metabolic. The non-communicable pattern was observed in both genders but only in the 20-44 years age group, while the aggregate pattern occurred only in middle-aged men. Cardio-metabolic and respiratory patterns were present in all age groups. Cardiovascular and mechanical/mental/metabolic patterns showed similar presentation in both men and women. CONCLUSIONS: Multi morbidity is a common occurrence among adults in Serbia, especially in the elderly. While several patterns may be explained by underlying pathophysiologies, some require further investigation and follow-up. Recognizing the complexity of multi-morbidity in Serbia is of great importance from both clinical and preventive perspectives given that it affects one-third of the population and may require adjustment of the healthcare system to address the needs of affected individuals. PMID- 26871937 TI - Mortality Patterns in Patients with Multiple Trauma: A Systematic Review of Autopsy Studies. AB - PURPOSE: A high percentage (50%-60%) of trauma patients die due to their injuries prior to arrival at the hospital. Studies on preclinical mortality including post mortem examinations are rare. In this review, we summarized the literature focusing on clinical and preclinical mortality and studies included post-mortem examinations. METHODS: A literature search was conducted using PubMed/Medline database for relevant medical literature in English or German language published within the last four decades (1980-2015). The following MeSH search terms were used in different combinations: "multiple trauma", "epidemiology", "mortality ", "cause of death", and "autopsy". References from available studies were searched as well. RESULTS: Marked differences in demographic parameters and injury severity between studies were identified. Moreover, the incidence of penetrating injuries has shown a wide range (between 4% and 38%). Both unimodal and bimodal concepts of trauma mortality have been favored. Studies have shown a wide variation in time intervals used to analyze the distribution of death. Thus, it is difficult to say which distribution is correct. CONCLUSIONS: We have identified variable results indicating bimodal or unimodal death distribution. Further more stundardized studies in this field are needed. We would like to encourage investigators to choose the inclusion criteria more critically and to consider factors affecting the pattern of mortality. PMID- 26871938 TI - Development and validation of a cyclodextrin-modified capillary electrophoresis method for the enantiomeric separation of vildagliptin enantiomers. AB - The enantiomers of vildagliptin, an orally available and selective dipeptidyl peptidase-4 inhibitor used for the treatment of type II diabetes, have been separated by CD-modified CZE, using uncoated fused-silica capillary. After screening 13 negatively charged CD derivatives as potential chiral selectors, sulfobutyl-ether-alpha-CD (SBE-alpha-CD) was selected for the enantioseparation. For the optimization, a factorial analysis study was performed by orthogonal experimental design. Six experimental factors were chosen as variable parameters: temperature, applied voltage, chiral selector and BGE concentrations, pH, and the parameters of the hydrodynamic injection. The optimized system still was not considered final as the second peak (S-enantiomer) migrated too close to the EOF, resulting in a potential inaccuracy during the determination of the chiral impurity. To fine-tune the method "one factor at a time" variation approach was applied. The final method (applying 15 degrees C capillary temperature, 40 mbar * 4 s hydrodynamic injection, 25 kV voltage in 75 mM acetate-Tris buffer [pH 4.75] containing 20 mM SBE-alpha-CD as chiral selector) was validated according to the ICH guideline. RSD percentage of the resolution value, migration times, and corrected peak areas were below 5% during testing repeatability and intermediate precision. LOD and LOQ values were found to be 2.5 and 7.5 MUg/mL, respectively. The method is considered linear in the 7.5-180 MUg/mL range for the R-enantiomer. The robustness of the method was justified using Plackett-Burmann statistical experimental design. PMID- 26871939 TI - Antidyskinetic effect of A2A and 5HT1A/1B receptor ligands in two animal models of Parkinson's disease. AB - BACKGROUND: The serotonin 5-HT1A/1B receptor agonist eltoprazine suppressed dyskinetic-like behavior in animal models of Parkinson's disease (PD) but simultaneously reduced levodopa (l-dopa)-induced motility. Moreover, adenosine A2A receptor antagonists, such as preladenant, significantly increased l-dopa efficacy in PD without exacerbating dyskinetic-like behavior. OBJECTIVES: We evaluated whether a combination of eltoprazine and preladenant may prevent or suppress l-dopa-induced dyskinesia, without impairing l-dopa's efficacy in relieving motor signs, in 2 PD models: unilateral 6-hydroxydopamine-lesioned rats and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. METHODS: Rotational behavior and abnormal involuntary movements, or disability and l-dopa induced dyskinesia were evaluated in 6-hydroxydopamine-lesioned rats and MPTP treated monkeys, respectively. Moreover, in the rodent striatum, induction of immediate-early gene zif-268, an index of long-term changes, was correlated with dyskinesia. RESULTS: In 6-hydroxydopamine-lesioned rats, combined administration of l-dopa (4 mg/kg) plus eltoprazine (0.6 mg/kg) plus preladenant (0.3 mg/kg) significantly prevented or reduced dyskinetic-like behavior without impairing motor activity. Zif-268 was increased in the striatum of rats treated with l-dopa and l-dopa plus preladenant compared with vehicle. In contrast, rats treated with eltoprazine (with or without preladenant) had lower zif-268 activation after chronic treatment in both the dyskinetic and l-dopa-non-primed groups. Moreover, acute l-dopa plus eltoprazine plus preladenant prevented worsening of motor performance (adjusting step) and sensorimotor integration deficit. Similar results were obtained in MPTP-treated monkeys, where a combination of preladenant with eltoprazine was found to counteract dyskinesia and maintain the full therapeutic effects of a low dose of l-dopa. CONCLUSIONS: Our results suggest a promising nondopaminergic pharmacological strategy for the treatment of dyskinesia in PD. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26871940 TI - Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program. AB - A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities. PMID- 26871942 TI - The Challenge of Planning Conservation Strategies in Threatened Seascapes: Understanding the Role of Fine Scale Assessments of Community Response to Cumulative Human Pressures. AB - Assessing the distribution and intensity of human threats to biodiversity is a prerequisite for effective spatial planning, harmonizing conservation purposes with sustainable development. In the Mediterranean Sea, the management of Marine Protected Areas (MPAs) is rarely based on explicit consideration of the distribution of multiple stressors, with direct assessment of their effects on ecosystems. This gap limits the effectiveness of protection and is conducive to conflicts among stakeholders. Here, a fine scale assessment of the potential effects of different combinations of stressors (both land- and marine-based) on vulnerable rocky habitats (i.e. lower midlittoral and shallow infralittoral) along 40 km of coast in the western Mediterranean (Ionian Sea) has been carried out. The study area is a paradigmatic example of socio-ecological interactions, where several human uses and conservation measures collide. Significant differences in the structure of assemblages according to different combinations of threats were observed, indicating distinct responses of marine habitats to different sets of human pressures. A more complex three-dimensional structure, higher taxon richness and beta-diversity characterized assemblages subject to low versus high levels of human pressure, consistently across habitats. In addition, the main drivers of change were: closeness to the harbour, water quality, and the relative extension of beaches. Our findings suggest that, although efforts to assess cumulative impacts at large scale may help in individuating priority areas for conservation purposes, the fact that such evaluations are often based on expert opinions and not on actual studies limits their ability to represent real environmental conditions at local scale. Systematic evaluations of local scale effects of anthropogenic drivers of change on biological communities should complement broad scale management strategies to achieve effective sustainability of human exploitation of marine resources. PMID- 26871941 TI - The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication. AB - Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471) of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection. PMID- 26871943 TI - Understanding HIV Risk Behavior among Tuberculosis Patients with Alcohol Use Disorders in Tomsk, Russian Federation. AB - Russian Federation's (RF) HIV epidemic is the fastest growing of any country. This study explores factors associated with high HIV risk behavior in tuberculosis (TB) patients with alcohol use disorders in Tomsk, RF. This analysis was nested within the Integrated Management of Physician-delivered Alcohol Care for TB Patients (IMPACT, trial number NCT00675961) randomized controlled study of integrating alcohol treatment into TB treatment in Tomsk. Demographics, HIV risk behavior (defined as participant report of high-risk intravenous drug use and/or multiple sexual partners with inconsistent condom use in the last six months), clinical data, alcohol use, depression and psychosocial factors were collected from 196 participants (161 male and 35 female) at baseline. Forty-six participants (23.5%) endorsed HIV risk behavior at baseline. Incarceration history(Odds Ratio (OR)3.93, 95% confidence interval (CI) 1.95, 7.95), age under 41 (OR:2.97, CI:1.46, 6.04), drug addiction(OR: 3.60 CI:1.10, 11.77), history of a sexually transmitted disease(STD)(OR 2.00 CI:1.02, 3.90), low social capital (OR:2.81 CI:0.99, 8.03) and heavier alcohol use (OR:2.56 CI: 1.02, 6.46) were significantly more likely to be associated with HIV risk behavior at baseline. In adjusted analysis, age under 41(OR: 4.93, CI: 2.10, 11.58), incarceration history(OR: 3.56 CI:1.55, 8.17) and STD history (OR: 3.48, CI: 1.5, 8.10) continued to be significantly associated with HIV risk behavior. Understanding HIV transmission dynamics in Russia remains an urgent priority to inform strategies to address the epidemic. Larger studies addressing sex differences in risks and barriers to protective behavior are needed. PMID- 26871945 TI - Effective growth-suppressive activity of maternal embryonic leucine-zipper kinase (MELK) inhibitor against small cell lung cancer. AB - Maternal embryonic leucine zipper kinase (MELK), that plays a critical role in maintenance of cancer stem cells (CSCs), is predominantly expressed in various types of human cancer including small cell lung cancer (SCLC). SCLC usually acquires resistance to anti-cancer drugs and portends dismal prognosis. We have delineated roles of MELK in development/progression of SCLC and examined anti tumor efficacy of OTS167, a highly potent MELK inhibitor, against SCLC. MELK expression was highly upregulated in both SCLC cell lines and primary tumors. siRNA-mediated MELK knockdown induced significant growth inhibition in SCLC cell lines. Concordantly, treatment with OTS167 exhibited strong cytotoxicity against eleven SCLC cell lines with IC50 of < 10 nM. As similar to siRNA knockdown, OTS167 treatment induced cytokinetic defects with intercellular bridges, and in some cell lines we observed formation of neuronal protrusions accompanied with increase of a neuronal differentiation marker (CD56), indicating that the compound induced differentiation of cancer cells to neuron-like cells. Furthermore, the MELK inhibition decreased its downstream FOXM1 activity and Akt expression in SCLC cells, and led to apoptotic cell death. OTS167 appeared to be more effective to CSCs as measured by the sphere formation assay, thus MELK inhibition might become a promising treatment modality for SCLC. PMID- 26871944 TI - Hyperinsulinemia enhances interleukin-17-induced inflammation to promote prostate cancer development in obese mice through inhibiting glycogen synthase kinase 3 mediated phosphorylation and degradation of interleukin-17 receptor. AB - Interleukin-17 (IL-17) plays important roles in inflammation, autoimmune diseases, and some cancers. Obese people are in a chronic inflammatory state with increased serum levels of IL-17, insulin, and insulin-like growth factor 1 (IGF1). How these factors contribute to the chronic inflammatory status that promotes development of aggressive prostate cancer in obese men is largely unknown. We found that, in obese mice, hyperinsulinemia enhanced IL-17-induced expression of downstream proinflammatory genes with increased levels of IL-17 receptor A (IL-17RA), resulting in development of more invasive prostate cancer. Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL 17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL 17RA, thus inhibiting IL-17-mediated inflammation. IL-17RA phosphorylation was reduced, while the IL-17RA levels were increased in the proliferative human prostate cancer cells compared to the normal cells. Insulin and IGF1 enhanced IL 17-induced inflammatory responses through suppressing GSK3, which was shown in the cultured cell lines in vitro and obese mouse models of prostate cancer in vivo. These findings reveal a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men. PMID- 26871946 TI - ERbeta decreases the invasiveness of triple-negative breast cancer cells by regulating mutant p53 oncogenic function. AB - Most (80%) of the triple-negative breast cancers (TNBCs) express mutant p53 proteins that acquire oncogenic activities including promoting metastasis. We previously showed that wild-type ERbeta (ERbeta1) impedes epithelial to mesenchymal transition (EMT) and decreases the invasiveness of TNBC cells. In the present study we searched for signaling pathways that ERbeta1 uses to inhibit EMT and invasion in TNBC cells. We show that ERbeta1 binds to and opposes the transcriptional activity of mutant p53 at the promoters of genes that regulate metastasis. p63 that transcriptionally cooperates with mutant p53 also binds to ERbeta1. Downregulation of p63 represses the epithelial phenotype of ERbeta1 expressing cells and alters the expression of mutant p53 target genes. These results describe a novel mechanism through which ERbeta1 can disturb oncogenic signals to inhibit aggressiveness in TNBCs. PMID- 26871947 TI - Longitudinal tracking of subpopulation dynamics and molecular changes during LNCaP cell castration and identification of inhibitors that could target the PSA /lo castration-resistant cells. AB - We have recently demonstrated that the undifferentiated PSA-/lo prostate cancer (PCa) cell population harbors self-renewing long-term tumor-propagating cells that are refractory to castration, thus representing a therapeutic target. Our goals here are, by using the same lineage-tracing reporter system, to track the dynamic changes of PSA-/lo and PSA+ cells upon castration in vitro, investigate the molecular changes accompanying persistent castration, and develop large numbers of PSA-/lo PCa cells for drug screening. To these ends, we treated LNCaP cells infected with the PSAP-GFP reporter with three regimens of castration, i.e., CDSS, CDSS plus bicalutamide, and MDV3100 continuously for up to ~21 months. We observed that in the first ~7 months, castration led to time-dependent increases in PSA-/lo cells, loss of AR and PSA expression, increased expression of cancer stem cell markers, and many other molecular changes. Meanwhile, castrated LNCaP cells became resistant to high concentrations of MDV3100, chemotherapeutic drugs, and other agents. However, targeted and medium-throughput library screening identified several kinase (e.g., IGF-1R, AKT, PI3K/mTOR, Syk, GSK3) inhibitors as well as the BCL2 inhibitor that could effectively sensitize the LNCaP-CRPC cells to killing. Of interest, LNCaP cells castrated for >7 months showed evidence of cyclic changes in AR and the mTOR/AKT signaling pathways potentially involving epigenetic mechanisms. These observations indicate that castration elicits numerous molecular changes and leads to enrichment of PSA-/lo PCa cells. The ability to generate large numbers of PSA-/lo PCa cells should allow future high-throughput screening to identify novel therapeutics that specifically target this population. PMID- 26871949 TI - Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation. AB - BACKGROUND: Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep((r)) . We aim to use these biomarkers to study the pathophysiology in IBS-C and FC. METHODS: Twenty-four FC and 24 IBS-C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep((r)) followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h. KEY RESULTS: Weighted average position score for FC was 3.6 (2.5-4.2), significantly greater than IBS-C at 2.0 (1.5-3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63 142) mL vs 39 (15-70) mL in IBS-C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS-C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS-C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep((r)) was greater for FC, being 295 (116 526) min, compared to IBS-C at 84 (49-111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep((r)) , r = 0.44, p < 0.01. Using a cut-off >230 min distinguishes FC from IBS-C with low sensitivity of 55% but high specificity of 95%. CONCLUSION & INFERENCES: Our objective MRI biomarkers allow a distinction between FC and IBS-C. PMID- 26871950 TI - Structural and Biochemical Insights into the Peptidoglycan Hydrolase Domain of FlgJ from Salmonella typhimurium. AB - FlgJ is a glycoside hydrolase (GH) enzyme belonging to the Carbohydrate Active enZyme (CAZy) family GH73. It facilitates passage of the bacterial flagellum through the peptidoglycan (PG) layer by cleaving the beta-1,4 glycosidic bond between N-acetylglucosamine and N-acetylmuramic acid sugars that comprise the glycan strands of PG. Here we describe the crystal structure of the GH domain of FlgJ from bacterial pathogen Salmonella typhimurium (StFlgJ). Interestingly, the active site of StFlgJ was blocked by the C-terminal alpha-helix of a neighbouring symmetry mate and a beta-hairpin containing the putative catalytic glutamic acid residue Glu223 was poorly resolved and could not be completely modeled into the electron density, suggesting it is flexible. Previous reports have shown that the GH73 enzyme Auto from Listeria monocytogenes is inhibited by an N-terminal alpha helix that may occlude the active site in similar fashion. To investigate if the C-terminus of StFlgJ inhibits GH activity, the glycolytic activity of StFlgJ was assessed with and without the C-terminal alpha-helix. The GH activity of StFlgJ was unaffected by the presence or absence of the alpha-helix, suggesting it is not involved in regulating activity. Removal of the C-terminal alpha-helix did, however, allow a crystal structure of the domain to be obtained where the flexible beta-hairpin containing residue Glu223 was entirely resolved. The beta hairpin was positioned such that the active site groove was fully solvent exposed, placing Glu223 nearly 21.6 A away from the putative general acid/base residue Glu184, which is too far apart for these two residues to coordinate glycosidic bond hydrolysis. The mobile nature of the StFlgJ beta-hairpin is consistent with structural studies of related GH73 enzymes, suggesting that a dynamic active site may be common to many GH73 enzymes, in which the active site opens to capture substrate and then closes to correctly orient active site residues for catalysis. PMID- 26871948 TI - Improving the clinical impact of biomaterials in cancer immunotherapy. AB - Immunotherapies for cancer have progressed enormously over the past few decades, and hold great promise for the future. The successes of these therapies, with some patients showing durable and complete remission, demonstrate the power of harnessing the immune system to eradicate tumors. However, the effectiveness of current immunotherapies is limited by hurdles ranging from immunosuppressive strategies employed by tumors, to inadequate specificity of existing therapies, to heterogeneity of disease. Further, the vast majority of approved immunotherapies employ systemic delivery of immunomodulators or cells that make addressing some of these challenges more difficult. Natural and synthetic biomaterials - such as biocompatible polymers, self-assembled lipid particles, and implantable biodegradable devices - offer unique potential to address these hurdles by harnessing the benefits of therapeutic targeting, tissue engineering, co-delivery, controlled release, and sensing. However, despite the enormous investment in new materials and nanotechnology, translation of these ideas to the clinic is still an uncommon outcome. Here we review the major challenges facing immunotherapies and discuss how the newest biomaterials and nanotechnologies could help overcome these challenges to create new clinical options for patients. PMID- 26871951 TI - Transstadial Effects of Bti on Traits of Aedes aegypti and Infection with Dengue Virus. AB - Most mosquito control efforts are primarily focused on reducing the adult population size mediated by reductions in the larval population, which should lower risk of disease transmission. Although the aim of larviciding is to reduce larval abundance and thus recruitment of adults, nonlethal effects on adults are possible, including transstadial effects on phenotypes of adults such as survival and pathogen infection and transmission. In addition, the mortality induced by control efforts may act in conjunction with other sources of mosquito mortality in nature. The consequences of these effects and interactions may alter the potential of the population to transmit pathogens. We tested experimentally the combined effects of a larvicide (Bacillus thuringiensis ssp. israelensis, Bti) and competition during the larval stages on subsequent Aedes aegypti (Linnaeus) traits, population performance, and susceptibility to dengue-1 virus infection. Ae. aegypti that survived exposure to Bti experienced accelerated development, were larger, and produced more eggs with increasing amounts of Bti, consistent with competitive release among surviving mosquitoes. Changing larval density had no significant interactive effect with Bti treatment on development and growth to adulthood. Larval density, but not Bti or treatment interaction, had a strong effect on survival of adult Ae. aegypti females. There were sharper declines in cumulative daily survival of adults from crowded than uncrowded larval conditions, suggesting that high competition conditions of larvae may be an impediment to transmission of dengue viruses. Rates of infection and dengue-1 virus disseminated infections were found to be 87+/-13% and 88+/-12%, respectively. There were no significant treatment effects on infection measurements. Our findings suggest that larvicide campaigns using Bti may reduce the number of emerged adults, but survivors will have a fitness advantage (growth, development, enhanced production of eggs) relative to conspecifics that are not under larvicide pressure. However, under most circumstances, these transstadial effects are unlikely to outweigh reductions in the adult population by Bti and altered risk of disease transmission. PMID- 26871952 TI - Predictors of alcohol-related negative consequences in adolescents: A systematic review of the literature and implications for future research. AB - OBJECTIVE: To conduct a systematic review of the literature examining risk and protective factors of alcohol related negative consequences (ARNCs) among adolescents. METHODS: We conducted a systematic search of original empirical articles published between January 1, 1990 and June 1, 2015. The qualitative synthesis was performed using the Theory of Triadic Influence as a framework. RESULTS: Fifty-two studies were reviewed. Intrapersonal (e.g., personality traits, drinking motives and expectancies, depression), interpersonal (e.g., parental and peer alcohol use, violence exposure) and attitudinal factors (e.g., media exposure to alcohol, religiosity) influence ARNCs. Emerging evidence of new trends contributing to ARNCs include ready mixed alcohol drinks and childhood trauma and abuse. CONCLUSIONS: Risk factors from all domains of influence were observed. More research is needed on protective factors and how alcohol use interacts with preventive factors in predicting ARNCs. The conceptualization of negative consequences varies significantly between studies and may impact the external validity of previous research. PMID- 26871953 TI - Decreased TUSC3 Promotes Pancreatic Cancer Proliferation, Invasion and Metastasis. AB - Pancreatic cancer is an aggressive disease with dismal prognosis. It is of paramount importance to understand the underlying etiological mechanisms and identify novel, consistent, and easy-to-apply prognostic factors for precision therapy. TUSC3 (tumor suppressor candidate 3) was identified as a potential tumor suppressor gene and previous study showed TUSC3 is decreased in pancreatic cancer at mRNA level, but its putative tumor suppressor function remains to be verified. In this study, TUSC3 expression was found to be suppressed both at mRNA and protein levels in cell line models as well as in clinical samples; decreased TUSC3 expression was associated with higher pathological TNM staging and poorer outcome. In three pairs of cell lines with different NF-kappaB activity, TUSC3 expression was found to be reversely correlated with NF-kappaB activity. TUSC3 silenced pancreatic cancer cell line exhibited enhanced potential of proliferation, migration and invasion. In an orthotopic implanted mice model, TUSC3 silenced cells exhibited more aggressive phenotype with more liver metastasis. In conclusion, the current study shows that decreased immunological TUSC3 staining is a factor prognostic of poor survival in pancreatic cancer patients and decreased TUSC3 promotes pancreatic cancer cell proliferation, invasion and metastasis. The reverse correlation between NF-kappaB activity and TUSC3 expression may suggest a novel regulation pattern for this molecule. PMID- 26871954 TI - Intra-Articular Corticosteroids in Addition to Exercise for Reducing Pain Sensitivity in Knee Osteoarthritis: Exploratory Outcome from a Randomized Controlled Trial. AB - OBJECTIVE: To assess the effects of one intra-articular corticosteroid injection two weeks prior to an exercise-based intervention program for reducing pain sensitivity in patients with knee osteoarthritis (OA). DESIGN: Randomized, masked, parallel, placebo-controlled trial involving 100 participants with clinical and radiographic knee OA that were randomized to one intra-articular injection on the knee with either 1 ml of 40 mg/ml methylprednisolone (corticosteroid) dissolved in 4 ml lidocaine (10 mg/ml) or 1 ml isotonic saline (placebo) mixed with 4 ml lidocaine (10 mg/ml). Two weeks after the injections all participants undertook a 12-week supervised exercise program. Main outcomes were changes from baseline in pressure-pain sensitivity (pressure-pain threshold [PPT] and temporal summation [TS]) assessed using cuff pressure algometry on the calf. These were exploratory outcomes from a randomized controlled trial. RESULTS: A total of 100 patients were randomized to receive either corticosteroid (n = 50) or placebo (n = 50); 45 and 44, respectively, completed the trial. Four participants had missing values for PPT and one for TS at baseline; thus modified intention-to-treat populations were analyzed. The mean group difference in changes from baseline at week 14 was 0.6 kPa (95% CI: -1.7 to 2.8; P = 0.626) for PPT and 384 mm*sec (95% CI: -2980 to 3750; P = 0.821) for TS. CONCLUSIONS: These results suggest that adding intra-articular corticosteroid injection 2 weeks prior to an exercise program does not provide additional benefits compared to placebo in reducing pain sensitivity in patients with knee OA. TRIAL REGISTRATION: EU clinical trials (EudraCT): 2012-002607-18. PMID- 26871957 TI - Enhancing nutrient recovery and compost maturity of coconut husk by vermicomposting technology. AB - Vermicompost was prepared by five different treatments from relatively resistant coconut husk mixed with either pig slurry or poultry manure. The recovery of vermicompost varied from 35% to 43% and it resulted in significant increase in pH, microbial biomass carbon, macro and micro nutrients concentration. Among the treatments highest relative N (1.6) and K (1.3) recovery were observed for 20% feedstock substitution by pig slurry while poultry manure substitution recorded highest P recovery (2.4). Compost maturity parameters significantly differed and well correlated. The characteristics of different treatments established the maturity indices as C/N 15-20; Cw<1.8; Cw/Norg<0.55; Lignin<10-12; CHA/CFA>1.5 and HI>15.0. The manurial value of the coconut husk compost was improved by feedstock substitution with pig slurry (80:20). The results revealed the technical feasibility of converting coconut husk into valuable compost by feedstock substitution with pig slurry. PMID- 26871956 TI - Intensification of microalgae drying and oil extraction process by vapor recompression and heat integration. AB - Reducing energy penalty caused by drying and oil extraction is the most critical challenge in microalgae biodiesel production. In this study, vapor recompression and heat integration are utilized to optimize the performance of wet microalgae drying and oil extraction. In the microalgae drying stage, the hot exhaust stream is recompressed and coupled with wet microalgae to recover the condensate heat. In the oil extraction stage, the exergy rate of recovered solvent is also elevated by compressor and then exchanged heat with feed and bottom stream in the distillation column. Energy and mass balance of the intensified process is investigated and compared with the conventional microalgae drying-extraction process. The simulation results indicated that the total energy consumption of the intensified process can be saved by 52.4% of the conventional route. PMID- 26871955 TI - Biomineralization-Inspired Synthesis of Copper Sulfide-Ferritin Nanocages as Cancer Theranostics. AB - It is essential to control the size and morphology of nanoparticles strictly in nanomedicine. Protein cages offer significant potential for templated synthesis of inorganic nanoparticles. In this study, we successfully synthesized ultrasmall copper sulfide (CuS) nanoparticles inside the cavity of ferritin (Fn) nanocages by a biomimetic synthesis method. The uniform CuS-Fn nanocages (CuS-Fn NCs) showed strong near-infrared absorbance and high photothermal conversion efficiency. In quantitative ratiometric photoacoustic imaging (PAI), the CuS-Fn NCs exhibited superior photoacoustic tomography improvements for real-time in vivo PAI of entire tumors. With the incorporation of radionuclide (64)Cu, (64)CuS Fn NCs also served as an excellent PET imaging agent with higher tumor accumulation compared to free copper. Following the guidance of PAI and PET, CuS Fn NCs were applied in photothermal therapy to achieve superior cancer therapeutic efficiency with good biocompatibility both in vitro and in vivo. The results demonstrate that the bioinspired multifunctional CuS-Fn NCs have potential as clinically translatable cancer theranostics and could provide a noninvasive, highly sensitive, and quantitative in vivo guiding method for cancer photothermal therapies in experimental and clinical settings. PMID- 26871958 TI - Novel carbon-rich additives preparation by degradative solvent extraction of biomass wastes for coke-making. AB - In this work, two extracts (Soluble and Deposit) were produced by degradative solvent extraction of biomass wastes from 250 to 350 degrees C. The feasibilities of using Soluble and Deposit as additives for coke-making were investigated for the first time. The Soluble and Deposit, having significantly higher carbon content, lower oxygen content and extremely lower ash content than raw biomasses. All Solubles and most of Deposits can melt completely at the temperature ranged from 80 to 120 degrees C and 140 to 180 degrees C, respectively. The additions of Soluble or Deposit into the coke-making coal significantly improved their thermoplastic properties with as high as 9 degrees C increase of the plastic range. Furthermore, the addition of Deposit or Soluble also markedly enhanced the coke quality through increasing coke strength after reaction (CSR) and reducing coke reactivity index (CRI). Therefore, the Soluble and Deposit were proved to be good additives for coke-making. PMID- 26871961 TI - All-graphene oxide device with tunable supercapacitor and battery behaviour by the working voltage. AB - We propose a new type of all-graphene oxide device. Reduced graphene oxide (rGO)/graphene oxide (GO)/rGO functions as both a supercapacitor and a battery, depending on the working voltage. The rGO/GO/rGO operates as a supercapacitor until 1.2 V. At greater than 1.5 V, it behaves as a battery using redox reaction. PMID- 26871960 TI - Proton magnetic resonance spectroscopy in juvenile myoclonic epilepsy: A systematic review and meta-analysis. AB - PURPOSE: We sought to systematically review and perform a meta-analysis of the magnetic resonance spectroscopy (MRS) findings regarding juvenile myoclonic epilepsy (JME). METHODS: We searched for studies in the PubMed, Web of Science, and Embase electronic databases. Two authors collected articles and extracted data independently. A meta-analysis was performed for diverse metabolites in different brain areas. The mean difference (MD) and 95% confidence interval (CI) were used to compare continuous variables. RESULTS: A decreased NAA/Cr was observed in the motor cortex (MD=0.14, 95%CI=0.09 to 0.20), and the NAA was reduced in the thalamus (MD=0.74, 95%CI=0.37 to 1.10) and the frontal lobe (MD=0.87, 95%CI=0.45 to 1.28); the GLX/Cr was increased in the insula (MD=-0.10, 95%CI=-0.14 to -0.06) and the striatum (MD=-0.11, 95%CI=-0.17 to -0.05). CONCLUSIONS: JME may be a multi-regional, thalamo-frontal network epilepsy rather than an idiopathic generalized epilepsy syndrome. PMID- 26871959 TI - The sensitivity and significance of lateralized interictal slow activity on magnetoencephalography in focal epilepsy. AB - OBJECTIVE: Asymmetric large-amplitude slow activity is sometimes observed on interictal electroencephalography (EEG) in epilepsy. However, few studies have examined slowing during magnetoencephalography (MEG) recordings, which are performed primarily to localize interictal spikes. Also, no prior investigations have compared the sensitivity of MEG to scalp EEG in detecting slow rhythms. METHODS: We performed a retrospective cohort study of focal epilepsy patients who received MEG followed by surgical resection at our institution. We examined MEG, simultaneous EEG, and long-term EEG recordings for prominent asymmetric slow activity (delta-range, 1-4 Hz), and evaluated post-operative seizure outcomes. RESULTS: We studied 132 patients with >= 1 year post-operative follow-up (mean, 3.6 years). Mean age was 27 (range, 3-68) years, and 55% of patients were male. Asymmetric large-amplitude slow wave activity was observed on interictal MEG in 21 of 132 (16%) patients. Interictal slowing lateralized to the hemisphere of resection in all but one (95%) patient. Among the 21 patients with interictal MEG slowing, 11 (52%) individuals had similarly lateralized EEG slowing, 7 patients had no EEG slowing, and 3 had bilateral symmetric EEG slowing. Meanwhile, none of the 111 patients without lateralized MEG slowing had asymmetric EEG slowing, suggesting significantly higher sensitivity of MEG versus EEG in detecting asymmetric slowing (chi(2)=63.4, p<0.001). MEG slowing was associated with shorter epilepsy duration with an odds ratio of 5.4 (1.7-17.0, 95% confidence interval). At last follow-up, 92 (70%) patients were seizure free (Engel I outcome), with no difference in seizure freedom rates between patients with (71%) or without (69%) asymmetric MEG slowing (chi(2)=0.4, p=0.99). SIGNIFICANCE: MEG has higher sensitivity than scalp EEG in detecting asymmetric slow activity in focal epilepsy, which reliably lateralizes to the epileptogenic hemisphere. Other uses of MEG beyond spike localization may further improve presurgical evaluations in epilepsy. PMID- 26871962 TI - Silver-Catalyzed Cascade Radical Cyclization: A Direct Approach to 3,4 Disubstituted Dihydroquinolin-2(1H)-ones through Activation of the P-H Bond and Functionalization of the C(sp(2))-H Bond. AB - A silver-catalyzed cascade cyclization of cinnamamides with diphenylphosphine oxide was developed, in which activation of the P-H bond and functionalization of the C(sp(2))-H bond occurred. A direct method for the synthesis of 3,4 disubstituted dihydroquinolin-2(1H)-ones was developed. PMID- 26871964 TI - Effects of soluble sulfide on zebrafish (Danio rerio) embryonic development. AB - Zebrafish embryos were used to investigate the developmental effects of sulfide. Mortality, teratogenic effects, and developmental parameters of early developmental embryos were recorded. The biodistribution of sulfide in developing zebrafish embryos and larvae were measured through fluorescence imaging. The influences of sulfide on the cardiac function and development velocity of zebrafish embryos were dependent on sulfide concentration. Heart rate and development velocity increased with exposure to lower sulfide concentrations, which may be attributed to the cardioprotective properties of H2S. Meanwhile, heart rate and development velocity decreased, whereas pericardial edema, yolk sac edema, and trunk abnormalities occurred with exposure to higher sulfide concentrations. Sulfide accumulated in the blastoderm of early developmental embryos and was then transported to the yolk sac and yolk extension with the embryonic development. Finally, sulfide was transferred from the yolk to the eyes of zebrafish larvae. The details of mechanism of sulfide toxicity require further research. PMID- 26871963 TI - Synthesis and Antibacterial Activity of Four Stereoisomers of the Spider Pathogenic Fungus Metabolite Torrubiellone D. AB - Four stereoisomers of the spider-pathogenic fungus metabolite torrubiellone D were synthesized for the first time in 10% overall yield starting from L-tyrosine or D-tyrosine. The 3-decatrienoyl side chain was assembled and attached via (E) selective HWE and Wittig olefinations. Their antibiotic activities against drug susceptible Escherichia coli strains differed considerably. PMID- 26871965 TI - Enhanced Thermoelectric Properties in the Counter-Doped SnTe System with Strained Endotaxial SrTe. AB - We report enhanced thermoelectric performance in SnTe, where significantly improved electrical transport properties and reduced thermal conductivity were achieved simultaneously. The former was obtained from a larger hole Seebeck coefficient through Fermi level tuning by optimizing the carrier concentration with Ga, In, Bi, and Sb dopants, resulting in a power factor of 21 MUW cm(-1) K( 2) and ZT of 0.9 at 823 K in Sn(0.97)Bi(0.03)Te. To reduce the lattice thermal conductivity without deteriorating the hole carrier mobility in Sn(0.97)Bi(0.03)Te, SrTe was chosen as the second phase to create strained endotaxial nanostructures as phonon scattering centers. As a result, the lattice thermal conductivity decreases strongly from ~2.0 Wm(-1) K(-1) for Sn(0.97)Bi(0.03)Te to ~1.2 Wm(-1) K(-1) as the SrTe content is increased from 0 to 5.0% at room temperature and from ~1.1 to ~0.70 Wm(-1) K(-1) at 823 K. For the Sn(0.97)Bi(0.03)Te-3% SrTe sample, this leads to a ZT of 1.2 at 823 K and a high average ZT (for SnTe) of 0.7 in the temperature range of 300-823 K, suggesting that SnTe is a robust candidate for medium-temperature thermoelectric applications. PMID- 26871966 TI - Benzothiadiazole-Mediated Induced Resistance to Colletotrichum musae and Delayed Ripening of Harvested Banana Fruit. AB - Benzothiadiazole (BTH) works as a plant activator. The effects of different BTH treatments and fungicides SPORGON on fruit ripening and disease incidence were investigated. The results showed that BTH treatment significantly delayed fruit ripening, maintained fruit firmness, color, and good fruit quality, and dramatically reduced the incidence of disease. BTH effectively inhibited the invasion and development of pathogenic bacteria and controlled the occurrence of disease. BTH treatment enhanced the activities of defense-related enzymes, including chitinase, phenylalanine ammonia-lyase, peroxidase, and polyphenol oxidase, increased the content of hydrogen peroxide and total antioxidant capacity, and reduced malondialdehyde content. Cellular structure analysis after inoculation confirmed that BTH treatment effectively maintained the cell structural integrity. SPORGON did not provide benefits for delaying fruit ripening or for the resistance system, while it can control the disease only during the earlier stage and not at later stages. PMID- 26871967 TI - Mono-(2-ethylhexyl) Phthalate Increases Oxidative Stress Responsive miRNAs in First Trimester Placental Cell Line HTR8/SVneo. AB - Phthalates, an endocrine disruptor group, cause oxidative stress (OS) in the placenta. However, no studies have reported OS-related miRNAs induced by phthalates. In the present study, we demonstrate that mono-(2-ethylhexyl) phthalate (MEHP) induces OS responsive miR-17-5p, miR-155-5p, and miR-126-3p in HTR8/SVneo in a dose- and time-dependent manner. Furthermore, MEHP altered the expression of phosphoinositide-3-kinase regulatory subunit 1alpha, phosphatase and tensin homolog, CDKN2A interacting protein, superoxide dismutase 2, and 3beta hydroxysterol-D24 reductase, which are involved in OS and predicted to be regulated by these miRNAs. Our results suggest that placental exposure to MEHP may result in aberrant miRNA expression leading to pregnancy complications. PMID- 26871969 TI - Effects of continuous vs interval exercise training on oxygen uptake efficiency slope in patients with coronary artery disease. AB - The oxygen uptake efficiency slope (OUES) is a submaximal index incorporating cardiovascular, peripheral, and pulmonary factors that determine the ventilatory response to exercise. The purpose of this study was to evaluate the effects of continuous exercise training and interval exercise training on the OUES in patients with coronary artery disease. Thirty-five patients (59.3+/-1.8 years old; 28 men, 7 women) with coronary artery disease were randomly divided into two groups: continuous exercise training (n=18) and interval exercise training (n=17). All patients performed graded exercise tests with respiratory gas analysis before and 3 months after the exercise-training program to determine ventilatory anaerobic threshold (VAT), respiratory compensation point, and peak oxygen consumption (peak VO2). The OUES was assessed based on data from the second minute of exercise until exhaustion by calculating the slope of the linear relation between oxygen uptake and the logarithm of total ventilation. After the interventions, both groups showed increased aerobic fitness (P<0.05). In addition, both the continuous exercise and interval exercise training groups demonstrated an increase in OUES (P<0.05). Significant associations were observed in both groups: 1) continuous exercise training (OUES and peak VO2 r=0.57; OUES and VO2 VAT r=0.57); 2) interval exercise training (OUES and peak VO2 r=0.80; OUES and VO2 VAT r=0.67). Continuous and interval exercise training resulted in a similar increase in OUES among patients with coronary artery disease. These findings suggest that improvements in OUES among CAD patients after aerobic exercise training may be dependent on peripheral and central mechanisms. PMID- 26871968 TI - Efficacy of a quadruple therapy regimen for Helicobacter pylori eradication after partial gastrectomy. AB - We aimed to evaluate the effectiveness and safety of bismuth-containing quadruple therapy plus postural change after dosing for Helicobacter pylori eradication in gastrectomized patients. We compared 76 gastric stump patients with H. pylori infection (GS group) with 50 non-gastrectomized H. pylori-positive patients who met the treatment indication (controls). The GS group was divided into GS group 1 and GS group 2. All groups were administered bismuth potassium citrate (220 mg), esomeprazole (20 mg), amoxicillin (1.0 g), and furazolidone (100 mg) twice daily for 14 days. GS group 1 maintained a left lateral horizontal position for 30 min after dosing. H. pylori was detected using rapid urease testing and histologic examination of gastric mucosa before and 3 months after therapy. Mucosal histologic manifestations were evaluated using visual analog scales of the updated Sydney System. GS group 1 had a higher prevalence of eradication than the GS group 2 (intention-to-treat [ITT]: P=0.025; per-protocol [PP]: P=0.030), and the control group had a similar prevalence. GS group 2 had a lower prevalence of eradication than controls (ITT: P=0.006; PP: P=0.626). Scores for chronic inflammation and activity declined significantly (P<0.001) 3 months after treatment, whereas those for atrophy and intestinal metaplasia showed no significant change. Prevalence of adverse reactions was similar among groups during therapy (P=0.939). A bismuth-containing quadruple therapy regimen plus postural change after dosing appears to be a relatively safe, effective, economical, and practical method for H. pylori eradication in gastrectomized patients. PMID- 26871970 TI - Implantation of muscle satellite cells overexpressing myogenin improves denervated muscle atrophy in rats. AB - This study evaluated the effect of muscle satellite cells (MSCs) overexpressing myogenin (MyoG) on denervated muscle atrophy. Rat MSCs were isolated and transfected with the MyoG-EGFP plasmid vector GV143. MyoG-transfected MSCs (MTMs) were transplanted into rat gastrocnemius muscles at 1 week after surgical denervation. Controls included injections of untransfected MSCs or the vehicle only. Muscles were harvested and analyzed at 2, 4, and 24 weeks post transplantation. Immunofluorescence confirmed MyoG overexpression in MTMs. The muscle wet weight ratio was significantly reduced at 2 weeks after MTM injection (67.17+/-6.79) compared with muscles injected with MSCs (58.83+/-5.31) or the vehicle (53.00+/-7.67; t=2.37, P=0.04 and t=3.39, P=0.007, respectively). The muscle fiber cross-sectional area was also larger at 2 weeks after MTM injection (2.63*103+/-0.39*103) compared with MSC injection (1.99*103+/-0.58*103) or the vehicle only (1.57*103+/-0.47*103; t=2.24, P=0.049 and t=4.22, P=0.002, respectively). At 4 and 24 weeks post-injection, the muscle mass and fiber cross sectional area were similar across all three experimental groups. Immunohistochemistry showed that the MTM group had larger MyoG-positive fibers. The MTM group (3.18+/-1.13) also had higher expression of MyoG mRNA than other groups (1.41+/-0.65 and 1.03+/-0.19) at 2 weeks after injection (t=2.72, P=0.04). Transplanted MTMs delayed short-term atrophy of denervated muscles. This approach can be optimized as a novel stand-alone therapy or as a bridge to surgical re innervation of damaged muscles. PMID- 26871971 TI - Cardioprotection against experimental myocardial ischemic injury using cornin. AB - Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 uM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt. PMID- 26871972 TI - Enhanced ubiquitination and proteasomal degradation of catalytically deficient human choline acetyltransferase mutants. AB - Choline acetyltransferase (ChAT) is essential for cholinergic neuron function as it mediates synthesis of the neurotransmitter acetylcholine. ChAT mutations have been linked to the neuromuscular disorder congenital myasthenic syndrome (CMS). One CMS-related ChAT mutation, V18M, reduces enzyme activity and cellular protein levels, and is positioned within a highly conserved proline-rich motif with the sequence 14 PKLPVPP20 . We demonstrate that N-terminal truncation that includes this proline-rich motif, as well as mutation of prolines-17/19 together to alanine (P17A/P19A), dramatically reduces ChAT steady-state protein levels and cellular activity when expressed in cholinergic SN56 neural cells. The in vitro activity of bacterially expressed recombinant P17A/P19A-ChAT is also reduced, although this is not caused by changes in protein secondary structure or thermal stability. Treatment of SN56 cells with the proteasome inhibitor MG132 increases cellular P17A/P19A-ChAT steady-state protein levels, and by immunoprecipitation we found that ChAT is ubiquitinated and that polyubiquitination of P17A/P19A-ChAT is increased compared to wild-type (WT) ChAT. Using a novel fluorescent biorthogonal pulse-chase protocol in SN56 cells, we determined that the protein half-life of P17A/P19A-ChAT (2.2 h) is substantially reduced compared to WT-ChAT (19.7 h). Lastly, we show that two CMS-related ChAT mutants (V18M and A513T) have enhanced ubiquitination, and that treatment with MG132 can partially restore both the steady-state protein levels as well as cellular activity of some CMS-mutant ChAT. These results identify a novel mechanism for regulation of ChAT through the ubiquitin-proteasome system that is influenced by the conserved N-terminal proline-rich motif of ChAT and may be implicated in CMS pathology. Choline acetyltransferase (ChAT) synthesizes acetylcholine in cholinergic neurons. In this study we find that steady-state protein levels of human 69-kDa ChAT are regulated by the ubiquitin-proteasome system. Mutation of a highly conserved N terminal proline-rich motif in human 69-kDa ChAT reduces both cellular ChAT protein levels, through enhanced ubiquitination and proteasomal degradation, and enzyme activity. Ubiquitination of catalytically deficient congenital myasthenic syndrome (CMS)-mutant ChAT is increased in cells, and importantly proteasome inhibition partially restores steady-state protein levels as well as cellular activity of some CMS-mutant ChAT proteins. PMID- 26871973 TI - In vitro study on apoptotic cell death by effective magnetic hyperthermia with chitosan-coated MnFe2O4. AB - Magnetic nanoparticles (MNPs) have been widely investigated as a hyperthermic agent for cancer treatment. In this study, thermally responsive Chitosan-coated MnFe2O4 (Chitosan-MnFe2O4) nanoparticles were developed to conduct localized magnetic hyperthermia for cancer treatment. Hydrophobic MnFe2O4 nanoparticles were synthesized via thermal decomposition and modified with 2,3 dimercaptosuccinic acid (DMSA) for further conjugation of chitosan. Chitosan MnFe2O4 nanoparticles exhibited high magnetization and excellent biocompatibility along with low cell cytotoxicity. During magnetic hyperthermia treatment (MHT) with Chitosan-MnFe2O4 on MDA-MB 231 cancer cells, the targeted therapeutic temperature was achieved by directly controlling the strength of the external AC magnetic fields. In vitro Chitosan-MnFe2O4-assisted MHT at 42 degrees C led to drastic and irreversible changes in cell morphology and eventual cellular death in association with the induction of apoptosis through heat dissipation from the excited magnetic nanoparticles. Therefore, the Chitosan-MnFe2O4 nanoparticles with high biocompatibility and thermal capability can be an effective nano mediated agent for MHT on cancer. PMID- 26871974 TI - Role of highly branched, high molecular weight polymer structures in directing uniform polymer particle formation during nanoprecipitation. AB - The new macromolecular architecture, hyperbranched polydendrons, are composed of a broad distribution of molecular weights and architectural variation; however, nanoprecipitation of these materials yields highly uniform, dendron-functional nanoparticles. By isolating different fractions of the diverse samples, the key role of the most highly branched structures in directing nucleation and growth has been explored and determined. PMID- 26871976 TI - Retraction of DNA Cell Biol: 31:1064-1069, 2012, DOI: 10.1089/dna.2011.1552. PMID- 26871975 TI - Dicopper(II) Metallacyclophanes with N,N'-2,6-Pyridinebis(oxamate): Solution Study, Synthesis, Crystal Structures, and Magnetic Properties. AB - The complexing ability of copper(II) in solution by the ligand N,N'-2,6 pyridinebis(oxamic acid) (H4mpyba, H4L) was determined through potentiometric and UV-vis spectroscopy at 25 degrees C and 0.15 M NaCl. The logarithms of the equilibrium constants for its copper(II) complexes according to the eqs 2H2L + 2Cu ? [Cu2(H2L)2], 2H2L + 2Cu ? [Cu2(H2L) (HL)] + H, 2H2L + 2Cu ? [Cu2(HL)2] + 2H, 2H2L + 2Cu ? [Cu2(HL)(L)] + 3H, and 2H2L + 2Cu ? [Cu2L2] + 4H were 12.02(7), 8.04(5), 1.26(6), -7.51(6), and -16.36(6), respectively. The knowledge of the solution behavior has supported the synthesis of three new compounds bearing the common building block Cu2L2(4-). Their formulas are (Me4N)4[Cu2(mpyba)2(H2O)2].H2O (1), (Me4N)4[K2Na2Cu4(mpyba)4(H2O)6.8].1.6H2O (2), and [Na6Cu2(mpyba)2Cl2(H2O)8].7H2O (3) (Me4N(+) = tetramethylammonium cation). The [Cu2(mpyba)2(H2O)2](4-) tetraanionic unit, which is present in 1, has a [3,3] metallacyclophane-type motif connected by two N-Cu-N bonds. In 2, a heterotrimetallic decanuclear nanocage is formed through front-to-front assembly of two [Cu2(mpyba)2](4-) units, which also coordinate to potassium(I) and sodium(I) cations by means of carboxylate oxygens from oxamate. The structure of 3 consists of heterobimetallic layers of formula [Na6Cu2(mpyba)2Cl2(H2O)8] and crystallization water molecules, which are interlinked by hydrogen bonds leading to a supramolecular three-dimensional network. The investigation of the magnetic properties of 1-3 in the temperature range 1.9-300 K shows the occurrence of ferromagnetic interactions between the dicopper(II) metallacyclophane unit [J = +6.85 (1), +7.40 (2), and +7.90 cm(-1) (3); H = -JSCu1.SCu2, where SCu1 = SCu2 = 1/2]. Theoretical calculations on 1-3 were carried to substantiate the nature and magnitude of the involved magnetic interactions and to support the occurrence of a spin polarization mechanism accounting for them. PMID- 26871977 TI - Effects of temperature, salt concentration, and the protonation state on the dynamics and hydrogen-bond interactions of polyelectrolyte multilayers on lipid membranes. AB - Polyelectrolyte multilayers, which consist of poly-l-lysines (PLL) and hyaluronic acids (HA), are simulated on phospholipid membranes with explicit water at different temperatures, salt concentrations, and protonation states of PLL that correspond to pH 7 or higher. PLL and HA polymers, which are initially sequentially deposited as three HA/PLL bilayers above the membrane, partially intermix with each other within 300 ns, and with a significant amount of water at almost half of its bulk density. With reduced protonation of amine groups of PLL, the polymers diffuse faster, especially at higher temperatures, and for 0% protonation, disperse into the water, due to the many fewer hydrogen bonds between PLL and HA polymers. When PLL is protonated, the addition of salt ions weakens electrostatic interactions between PLL and HA and, at 0.5 M NaCl, eventually reduces the number of hydrogen bonds, which in experiments leads to hole formation inside the PLL/HA film. Multilayers are stabilized by hydrogen bonds, primarily between charged groups and to a lesser extent between uncharged groups. PLL and HA also electrostatically interact with lipid head groups of membranes which reduces the lateral mobility of membrane lipids, to an extent dependent on the salt concentration. These findings help quantitate the effects of temperature, salt, and the protonation state (or pH) on the stability and dynamics of multilayers and membranes, and show trends that compare favorably with the experimental observations of the swelling of multilayers. PMID- 26871981 TI - Specific allergen immunotherapy for the treatment of atopic eczema. AB - BACKGROUND: Specific allergen immunotherapy (SIT) is a treatment that may improve disease severity in people with atopic eczema (AE) by inducing immune tolerance to the relevant allergen. A high quality systematic review has not previously assessed the efficacy and safety of this treatment. OBJECTIVES: To assess the effects of specific allergen immunotherapy (SIT), including subcutaneous, sublingual, intradermal, and oral routes, compared with placebo or a standard treatment in people with atopic eczema. SEARCH METHODS: We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), LILACS (from 1982), Web of ScienceTM (from 2005), the Global Resource of EczemA Trials (GREAT database), and five trials databases. We searched abstracts from recent European and North American allergy meetings and checked the references of included studies and review articles for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of specific allergen immunotherapy that used standardised allergen extracts in people with AE. DATA COLLECTION AND ANALYSIS: Two authors independently undertook study selection, data extraction (including adverse effects), assessment of risk of bias, and analyses. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We identified 12 RCTs for inclusion in this review; the total number of participants was 733. The interventions included SIT in children and adults allergic to either house dust mite (10 trials), grass pollen, or other inhalant allergens (two trials). They were administered subcutaneously (six trials), sublingually (four trials), orally, or intradermally (two trials). Overall, the risk of bias was moderate, with high loss to follow up and lack of blinding as the main methodological concern.Our primary outcomes were 'Participant- or parent reported global assessment of disease severity at the end of treatment'; 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'; and 'Adverse events, such as acute episodes of asthma or anaphylaxis'. SCORing Atopic Dermatitis (SCORAD) is a means of measuring the effect of atopic dermatitis by area (A); intensity (B); and subjective measures (C), such as itch and sleeplessness, which we used.For 'Participant- or parent-reported global assessment of disease severity at the end of treatment', one trial (20 participants) found improvement in 7/9 participants (78%) treated with the SIT compared with 3/11 (27%) treated with the placebo (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.02 to 7.96; P = 0.04). Another study (24 participants) found no difference: global disease severity improved in 8/13 participants (62%) treated with the SIT compared with 9/11 (81%) treated with the placebo (RR 0.75, 95% CI 0.45 to 1.26; P = 0.38). We did not perform meta-analysis because of high heterogeneity between these two studies. The quality of the evidence was low.For 'Participant- or parent-reported specific symptoms of eczema, by subjective measures', two trials (184 participants) did not find that the SIT improved SCORAD part C (mean difference (MD) -0.74, 95% CI -1.98 to 0.50) or sleep disturbance (MD -0.49, 95% CI -1.03 to 0.06) more than placebo. For SCORAD part C itch severity, these two trials (184 participants) did not find that the SIT improved itch (MD -0.24, 95% CI -1.00 to 0.52). One other non-blinded study (60 participants) found that the SIT reduced itch compared with no treatment (MD 4.20, 95% CI -3.69 to -4.71) and reduced the participants' overall symptoms (P < 0.01), but we could not pool these three studies due to high heterogeneity. The quality of the evidence was very low.Seven trials reported systemic adverse reactions: 18/282 participants (6.4%) treated with the SIT had a systemic reaction compared with 15/210 (7.1%) with no treatment (RR 0.78, 95% CI 0.41 to 1.49; the quality of the evidence was moderate). The same seven trials reported local adverse reactions: 90/280 participants (32.1%) treated with the SIT had a local reaction compared with 44/204 (21.6%) in the no treatment group (RR 1.27, 95% CI 0.89 to 1.81). As these had the same study limitations, we deemed the quality of the evidence to also be moderate.Of our secondary outcomes, there was a significant improvement in 'Investigator- or physician-rated global assessment of disease severity at the end of treatment' (six trials, 262 participants; RR 1.48, 95% CI 1.16 to 1.88). None of the studies reported our secondary outcome 'Parent- or participant-rated eczema severity assessed using a published scale', but two studies (n = 184), which have been mentioned above, used SCORAD part C, which we included as our primary outcome 'Participant- or parent-reported specific symptoms of eczema, by subjective measures'.Our findings were generally inconclusive because of the small number of studies. We were unable to determine by subgroup analyses a particular type of allergen or a particular age or level of disease severity where allergen immunotherapy was more successful. We were also unable to determine whether sublingual immunotherapy was associated with more local adverse reactions compared with subcutaneous immunotherapy. AUTHORS' CONCLUSIONS: Overall, the quality of the evidence was low. The low quality was mainly due to the differing results between studies, lack of blinding in some studies, and relatively few studies reporting participant-centred outcome measures. We found limited evidence that SIT may be an effective treatment for people with AE. The treatments used in these trials were not associated with an increased risk of local or systemic reactions. Future studies should use high quality allergen formulations with a proven track record in other allergic conditions and should include participant-reported outcome measures. PMID- 26871982 TI - Pharmacological and non-pharmacological interventions for reducing rocuronium bromide induced pain on injection in children and adults. AB - BACKGROUND: Rocuronium bromide is a routinely used muscle relaxant in anaesthetic practice. Its use, however, is associated with intense pain on injection. While it is well established that rocuronium bromide injection causes pain in awake patients, anaesthetized patients also tend to show withdrawal movements of the limbs when this muscle relaxant is administered. Various strategies, both pharmacological and non-pharmacological, have been studied to reduce the incidence and severity of pain on rocuronium bromide injection. We wanted to find out which of the existing modalities was best to reduce pain on rocuronium injection. OBJECTIVES: The objectives of this review were to assess the ability of both pharmacological and non-pharmacological interventions to reduce or eliminate the pain that accompanies rocuronium bromide administration. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 7), MEDLINE via Ovid SP (1966 to July 2013) and EMBASE via Ovid SP (1980 to July 2013). We also searched specific websites. We reran the searches in February 2015 and will deal with the 11 studies of interest found through this search when we update the review. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared the use of any drug or a non pharmacological method with control patients, or those receiving no treatment to reduce the severity of pain with rocuronium injection. Our primary outcome was pain on rocuronium bromide injection measured by a pain score assessment. Our secondary outcomes were rise in heart rate and blood pressure following administration of rocuronium and adverse events related to the interventions. DATA COLLECTION AND ANALYSIS: We used the standardized methods for conducting a systematic review as described in the Cochrane Handbook for Systematic Reviews of Interventions. Two authors independently extracted details of trial methodology and outcome data from reports of all trials considered eligible for inclusion. We made all analyses on an intention-to-treat basis. We used a fixed-effect model where there was no evidence of significant heterogeneity between studies and a random-effects model if heterogeneity was likely. MAIN RESULTS: We included 66 studies with 7840 participants in the review, though most analyses were based on data from fewer participants. In total there are 17 studies awaiting classification. No studies were at a low risk of bias. We noted substantial statistical and clinical heterogeneity between trials. Most of the studies reported the primary outcome pain as assessed by verbal response from participants in an awake state but some trials reported withdrawal of the injected limb as a proxy for pain after induction of anaesthesia in response to rocuronium administration. Few studies reported adverse events and no study reported heart rate and blood pressure changes after administration of rocuronium. Lidocaine was the most commonly studied intervention drug, used in 29 trials with 2256 participants. The risk ratio (RR) of pain on injection if given lidocaine compared to placebo was 0.23 (95% confidence interval (CI) 0.17 to 0.31; I2 = 65%, low quality of evidence). The RR of pain on injection if fentanyl and remifentanil were given compared to placebo was 0.42 (95% CI 0.26 to 0.70; I2 = 79%, low quality of evidence) and (RR 0.10, 95% CI 0.04 to 0.26; I2 = 74%, low quality of evidence), respectively. Pain on injection of intervention drugs was reported with the use of lidocaine and acetaminophen in one study. Cough was reported with the use of fentanyl (one study), remifentanil (five studies, low quality evidence) and alfentanil (one study). Breath holding and chest tightness were reported with the use of remifentanil in two studies (very low quality evidence) and one study (very low quality evidence), respectively. The overall rate of complications was low. AUTHORS' CONCLUSIONS: The evidence to suggest that the most commonly investigated pharmacological interventions reduce pain on injection of rocuronium is of low quality due to risk of bias and inconsistency. There is low or very low quality evidence for adverse events, due to risk of bias, inconsistency and imprecision of effect. We did not compare the various interventions with one another and so cannot comment on the superiority of one intervention over another. Complications were reported more often with use of opioids. PMID- 26871978 TI - Metabolic Effects of a Commonly Used Combined Hormonal Oral Contraceptive in Women With and Without Polycystic Ovary Syndrome. AB - BACKGROUND: Data on combined hormonal oral contraceptives' (OCs) effects on metabolic changes in women with polycystic ovary syndrome (PCOS) have been conflicting and were predominantly based on OCs with cyproterone acetate (unavailable in the United States) Most studies did not include normal women as controls. We compared metabolic changes before and after an OC commonly used in the United States between women with and without PCOS. METHODS: Ten PCOS and 20 control women took ethinyl estradiol 35 MUg and norgestimate 0.18/0.215/0.25 mg. Fasting glucose and insulin, area-under-the-curve (AUC) glucose and insulin, insulin sensitivity (homeostatic model assessment of insulin sensitivity index [HOMA-ISI] and Matsuda index), insulinogenic index (Deltainsulin0-30 minutes/Deltaglucose0-30 minutes), blood pressure, and lipids were evaluated at baseline and after three cycles of OC. RESULTS: At baseline, PCOS women had lower insulin sensitivity (Matsuda index p = 0.0093, HOMA-ISI p = 0.0397), higher fasting insulin (p = 0.0495), fasting glucose (p = 0.0393), AUC insulin (p = 0.0023), and triglycerides (p = 0.0044) versus controls. Baseline AUC glucose did not differ between PCOS women and controls. After 3 months of OC use, glucose tolerance worsened in PCOS women versus controls (p = 0.0468). Higher baseline androgens were predictive of worsened glucose tolerance, and a reduction of AUC insulin during OC use. The insulinogenic index significantly decreased in PCOS women (p < 0.01), while fasting insulin and insulin resistance significantly worsened in control women. CONCLUSION: Women with PCOS exhibited worsened glucose tolerance (demonstrated by AUC glucose) after 3 months of a commonly used OC compared with control women. Larger studies with longer follow-up should confirm these findings. PMID- 26871983 TI - Influence of a Brazilian wild green propolis on the enamel mineral loss and Streptococcus mutans' count in dental biofilm. AB - OBJECTIVE: This study investigated the anti-demineralizing and antibacterial effects of a propolis ethanolic extract (EEP) against Streptococcus mutans dental biofilm. DESIGN: Blocks of sound bovine enamel (n=24) were fixed on polystyrene plates. S. mutans inoculum (ATCC 25175) and culture media were added (48 h-37 degrees C) to form biofilm. Blocks with biofilm received daily treatment (30 MUL/1 min), for 5 days, as following: G1 (EEP 33.3%); G2 (chlorhexidine digluconate 0.12%); G3 (ethanol 80%); and G4 (Milli-Q water). G5 and G6 were blocks without biofilm that received only EEP and Milli-Q water, respectively. Final surface hardness was evaluated and the percentage of hardness loss (%HL) was calculated. The EEP extract pH and total solids were determined. S. mutans count was expressed by log10 scale of Colony-Forming Units (CFU/mL). One way ANOVA was used to compare results which differed at a 95% significance level. RESULTS: G2 presented the lowest average %HL value (68.44% +/- 12.98) (p=0.010), while G4 presented the highest (90.49% +/- 5.38%HL) (p=0.007). G1 showed %HL (84.41% +/- 2.77) similar to G3 (87.80% +/- 6.89) (p=0.477). Groups G5 and G6 presented %HL=16.11% +/- 7.92 and 20.55% +/- 10.65; respectively (p=0.952). G1 and G4 differed as regards to S. mutans count: 7.26 +/- 0.08 and 8.29 +/- 0.17 CFU/mL, respectively (p=0.001). The lowest bacterial count was observed in chlorhexidine group (G2=6.79 +/- 0.10 CFU/mL) (p=0.043). There was no difference between S. mutans count of G3 and G4 (p=0.435). The EEP showed pH 4.8 and total soluble solids content=25.9 Brix. CONCLUSION: The EEP seems to be a potent antibacterial substance against S. mutans dental biofilm, but presented no inhibitory action on the de-remineralization of caries process. PMID- 26871984 TI - Altered distribution of Ghrelin protein in mice molar development. AB - OBJECTIVE: Ghrelin, an appetite-stimulating hormone, plays diverse regulatory functions in cell growth, proliferation, differentiation and apoptosis during mammalian development. There is limited information currently available regarding Ghrelin expression during mammalian tooth development, thus we aimed to establish the spatiotemporal expression of Ghrelin during murine molar odontogenesis. DESIGN: Immunohistochemistry was performed to detect the expression pattern of Ghrelin in mandible molar from E15.5 to PN7 during murine tooth development. RESULTS: The results showed that Ghrelin initially expressed in the inner enamel epithelium and the adjacent mesenchymal cells below, further with persistent expression in the ameloblasts and odontoblasts throughout the following developmental stages. In addition, Ghrelin was also present in Hertwig's epithelial root sheath at the beginning of tooth root formation. CONCLUSIONS: These results suggest that Ghrelin was present in tooth organs throughout the stages of tooth development, especially in ameloblasts and odontoblasts with little spatiotemporal expression differences. However, the potential regulatory roles of this hormone in tooth development still need to be validated by functional studies. PMID- 26871985 TI - Standardisation of sheep model for endodontic regeneration/revitalisation research. AB - OBJECTIVE: Different endodontic regeneration/revitalisation protocols have been suggested for the treatment of immature permanent teeth with pulp necrosis. Many aspects of these protocols require further investigating necessitating a suitable standardised animal model for research purposes. The focus of this study was to examine the anatomy and histology of sheep teeth at different stages of development to find an appropriate dental age for endodontic regeneration/revitalisation research. DESIGN: Sheep teeth at mature and immature dental ages were investigated. Standardized radiography, computed tomography, and histology were used to measure root length, apical-third dentine thickness and apex diameter, and to evaluate tissue development stages. RESULTS: A mature sheep tooth has an apical area which consists of a major foramen, intermediate dilatation and minor foramen. From the time of eruption to maturation no major changes occur in the incisor root lengths, but the apical foramen width decreases and the dentinal wall thickness increases. The two-tooth age exhibited the most similar features to that of an immature permanent human tooth. CONCLUSION: Sheep appears to be an appropriate animal model for endodontic regeneration/revitalization research with similar dimension and characteristics to human anterior teeth. Each dental age has its advantages and disadvantages. The two-tooth age showed the most favourable criteria making this age the most suitable for in vivo regeneration/revitalisation research. PMID- 26871986 TI - US of the Peripheral Nerves of the Lower Extremity: A Landmark Approach. AB - Ultrasonography (US) is commonly used to assess the peripheral nerves of the lower extremity because of its many advantages over magnetic resonance (MR) imaging. The most obvious advantages over MR imaging are superior soft-tissue resolution, low cost, portability, lack of magnetic susceptibility artifact, and the ability to image patients who cannot undergo MR imaging. US has been shown to have equal specificity and greater sensitivity than MR imaging in the evaluation of peripheral nerves. Additional benefits are the capability of real-time and dynamic imaging, and the ability to scan an entire extremity quickly without the need for a patient to lie motionless for long periods of time, as with MR imaging. Any abnormal findings can be easily compared against the contralateral side. Published literature has shown that US has clinical utility in patients suspected of having peripheral nerve disease: US can be used to guide diagnostic and therapeutic decisions, as well as help confirm electrodiagnostic findings. Common indications for lower extremity peripheral nerve US are the evaluation for injury due to penetrating trauma, entrapment by scar tissue, or tumor. To confidently perform US of the peripheral nerves of the lower extremity, it is important to gain a thorough knowledge of anatomic landmarks and the course of each nerve. Readers who may not be familiar with US will be introduced to the basics of scanning the peripheral nerves of the lower extremity. Important anatomic landmarks and common sites of injury and entrapment will be reviewed. PMID- 26871987 TI - Renal Arteriovenous Shunts: Clinical Features, Imaging Appearance, and Transcatheter Embolization Based on Angioarchitecture. AB - Renal arteriovenous (AV) shunt, a rare pathologic condition, is divided into two categories, traumatic and nontraumatic, and can cause massive hematuria, retroperitoneal hemorrhage, pain, and high-output heart failure. Although transcatheter embolization is a less-invasive and effective treatment option, it has a potential risk of complications, including renal infarction and pulmonary embolism, and a potential risk of recanalization. The successful embolization of renal AV shunt requires a complete occlusion of the shunted vessel while preventing the migration of embolic materials and preserving normal renal arterial branches, which depends on the selection of adequate techniques and embolic materials for individual cases, based on the etiology and imaging angioarchitecture of the renal AV shunts. A classification of AV malformations in the extremities and body trunk could precisely correspond with the angioarchitecture of the nontraumatic renal AV shunts. The selection of techniques and choice of adequate embolic materials such as coils, vascular plugs, and liquid materials are determined on the basis of cause (eg, traumatic vs nontraumatic), the classification, and some other aspects of the angioarchitecture of renal AV shunts, including the flow and size of the fistulas, multiplicity of the feeders, and endovascular accessibility to the target lesions. Computed tomographic angiography and selective digital subtraction angiography can provide precise information about the angioarchitecture of renal AV shunts before treatment. Color Doppler ultrasonography and time-resolved three-dimensional contrast-enhanced magnetic resonance angiography represent useful tools for screening and follow-up examinations of renal AV shunts after embolization. In this article, the classifications, imaging features, and an endovascular treatment strategy based on the angioarchitecture of renal AV shunts are described. PMID- 26871988 TI - Birth Prevalence of Sickle Cell Trait and Sickle Cell Disease in Shelby County, TN. AB - BACKGROUND: Accurate quantification of the regional burden of sickle cell disease (SCD) is vital to allocating health-related resources. Shelby County, TN, which includes the city of Memphis and the regional pediatric SCD treatment center at St. Jude Children's Research Hospital, is home to a large population of African Americans. PROCEDURE: We postulated that the regional birth prevalence of SCD in Shelby County, TN, would differ from national rates. Using data from 2002 to 2012, we estimated the birth prevalence of SCD and sickle cell trait (SCT) in Shelby County and evaluated the distribution of SCD cases by ZIP code of residence with geographic information systems (GIS). RESULTS: The prevalence of SCD in African Americans was 1/287 (95% confidence interval [CI]: 1/323, 1/256) live births, significantly higher than the nationally reported 1/350 -1/500. The prevalence of SCT in African Americans was 1/14.7 (95% CI: 1/15.0, 1/14.3) live births, significantly lower than the nationally reported 1/12. We found that 48% of the SCD cases resided in only six of the 37 residential ZIP codes, and using GIS mapping there were two clusters composed of two and four adjacent urban ZIP codes. SCT cases were also centered predominantly in the same two clusters, but slightly more dispersed. CONCLUSIONS: Recent Shelby County birth prevalence estimates differ substantially from national estimates with higher SCD and lower SCT than expected. Preliminary evidence suggests substantial clustering in two small geographic urban areas within Shelby County that may provide target areas for educational and outreach services. PMID- 26871989 TI - Musculoskeletal Asymmetry in Football Athletes: A Product of Limb Function over Time. AB - PURPOSE: Asymmetrical loading patterns are commonplace in football sports. Our aim was to examine the influence of training age and limb function on lower-body musculoskeletal morphology. METHODS: Fifty-five elite football athletes were stratified into less experienced (<=3 yr; n = 27) and more experienced (>3 yr; n = 28) groups by training age. All athletes underwent whole-body dual-energy x-ray absorptiometry scans and lower-body peripheral quantitative computed tomography tibial scans on the kicking and support limbs. RESULTS: Significant interactions between training age and limb function were evident across all skeletal parameters (F16, 91 = 0.182, P = 0.031, Wilks Lambda = 0.969). Asymmetries between limbs were significantly larger in the more experienced players than the less experienced players for tibial mass (P <= 0.044, d >= 0.50), total cross sectional area (P <= 0.039, d >= 0.53), and stress-strain indices (P <= 0.050, d >= 0.42). No significant asymmetry was evident for total volumetric density. More experienced players also exhibited greater lower-body tibial mass (P <= 0.001, d >= 1.22), volumetric density (P <= 0.009, d >= 0.79), cross-sectional area (P <= 0.387, d >= 0.21), stress-strain indices (P <= 0.012, d >= 0.69), fracture loads (P <= 0.018, d >= 0.57), and muscle mass and cross-sectional area (P <= 0.016, d >= 0.68) than less experienced players. CONCLUSIONS: Asymmetries were evident in athletes as a product of limb function over time. Chronic exposure to routine high-impact gravitational loads afforded to the support limb preferentially improved bone mass and structure (cross-sectional area and cortex thickness) as potent contributors to bone strength relative to the high-magnitude muscular loads predominantly afforded to the kicking limb. PMID- 26871990 TI - The Effect of Head Impact Location on Day of Diagnosed Concussion in College Football. AB - INTRODUCTION: Scientists and clinicians have attempted to identify and understand biomechanical factors that influence concussion likelihood. The effect of impact frequency to a given head location before the concussion has not been evaluated. The purpose of this study was to compare the frequency of impacts to a given head location on days of diagnosed concussion to the frequency of impacts to a given head location before kinematically matched nonconcussive impacts. METHODS: Head impact data were gathered from 33 Division I National Collegiate Athletic Association football players. Twenty-four concussions were identified and matched with impacts of similar kinematic and injury criterion values (linear acceleration, rotational acceleration, Gadd severity index, and head injury criterion) that occurred during the same event type (game, practice, or scrimmage). In addition, these same matching criteria were used to match all players to the closest kinematic/same player group. All impacts within a session before the impact of interest (concussive or matched impact) were analyzed. RESULTS: On days of diagnosed concussion, the concussive group sustained a lower percentage of impacts to the front of the head (34.5%) and a greater frequency of impacts to the sides (19.6%) and top (18.9%) of the head (chi(3) = 10.23, P = 0.017) as compared with the matched nonconcussive group (front = 42.5%, sides = 16.6%, top = 14.0%). No significant difference in frequency was found in impacts to the back of the head. CONCLUSION: It may be more difficult to mitigate concussive forces sustained in impacts to the top and sides of the head than the front of the head. These findings fall in line with previous research demonstrating that reduced impact magnitudes may lessen concussion risk. Studying appropriate training paradigms to develop safer playing techniques on the field is warranted. PMID- 26871992 TI - Statistical investigation of the length-dependent deviations in the electrical characteristics of molecular electronic junctions fabricated using the direct metal transfer method. AB - We fabricated and analyzed the electrical transport characteristics of vertical type alkanethiolate molecular junctions using the high-yield fabrication method that we previously reported. The electrical characteristics of the molecular electronic junctions were statistically collected and investigated in terms of current density and transport parameters based on the Simmons tunneling model, and we determined representative current-voltage characteristics of the molecular junctions. In particular, we examined the statistical variations in the length dependent electrical characteristics, especially the Gaussian standard deviation sigma of the current density histogram. From the results, we found that the magnitude of the sigma value can be dependent on the individual molecular length due to specific microscopic structures in the molecular junctions. The probable origin of the molecular length-dependent deviation of the electrical characteristics is discussed. PMID- 26871991 TI - Childhood Physical Activity and Adulthood Earnings. AB - PURPOSE: This study examined the associations between childhood physical activity level and adulthood earnings. METHODS: The data were drawn from the ongoing longitudinal Young Finns Study, which was combined with register-based Finnish Longitudinal Employer-Employee Data and register-based parents' background information from the Longitudinal Population Census of Statistics Finland. The study consisted of children who were 9 yr (n = 1257, 52% boys), 12 yr (n = 1662, 51% boys), and 15 yr (n = 1969, 49% boys) of age at the time when physical activity was measured. The children were followed until 2010, when they were between 33 and 45 yr old. Leisure-time physical activity in childhood was self reported, whereas earnings in adulthood were register based and covered over a 10 yr period from 2000 to 2010. Ordinary least squares models were used to analyze the relationship between physical activity and earnings. RESULTS: Childhood physical activity level was positively associated with long-term earnings among men (P < 0.001). In more detail, a higher level of leisure-time physical activity at the age of 9, 12, and 15 yr was associated with an approximate 12%-25% increase in average annual earnings over a 10-yr period. The results were robust to controlling, e.g., an individual's chronic conditions and body fat, parents' education and physical activity, and family income. Among women, no relation was observed. CONCLUSIONS: The findings provide evidence that childhood physical activity can have far-reaching positive effects on adulthood earnings. Possibilities for improving physical activity during childhood may not only promote health but also affect long-term labor market outcomes. PMID- 26871993 TI - 3D Printed PEG-Based Hybrid Nanocomposites Obtained by Sol-Gel Technique. AB - In this work, three-dimensional (3D) structured hybrid materials were fabricated combining 3D printing technology with in situ generation of inorganic nanoparticles by sol-gel technique. Those materials, consisting of silica nanodomains covalently interconnected with organic polymers, were 3D printed in complex multilayered architectures, incorporating liquid silica precursors into a photocurable oligomer in the presence of suitable photoinitiators and exposing them to a digital light system. A post sol-gel treatment in acidic vapors allowed the in situ generation of the inorganic phase in a dedicated step. This method allows to build hybrid structures operating with a full liquid formulation without meeting the drawbacks of incorporating inorganic powders into 3D printable formulations. The influence of the generated silica nanoparticle on the printed objects was deeply investigated at macro- and nanoscale; the resulting light hybrid structures show improved mechanical properties and, thus, have a huge potential for applications in a variety of advanced technologies. PMID- 26871994 TI - Adipose Tissue Hypoxia, Inflammation, and Fibrosis in Obese Insulin-Sensitive and Obese Insulin-Resistant Subjects. AB - CONTEXT: A substantial number of obese individuals are relatively insulin sensitive and the etiology for this variation remains unknown. OBJECTIVE: The primary objective was to detect factors in adipose tissue differentiating obese insulin-sensitive (OBIS) from obese insulin-resistant (OBIR) individuals and investigate whether adipose tissue hypoxia is a contributing factor in the pathogenesis of insulin resistance. DESIGN AND SETTING: This was a cross sectional study in the general community. PARTICIPANTS: Subjects consisted of nondiabetic OBIS and OBIR subjects with similar body mass index, age, and total body fat but different insulin sensitivity index as well as lean insulin sensitive subjects. INTERVENTIONS(S): There were no interventions. MAIN OUTCOME MEASURE(S): We examined adipocytokines and the expression of candidate genes regulating hypoxia, inflammation, and lipogenesis in adipose tissue and adipose tissue oxygenation. RESULTS: OBIS subjects had increased plasma adiponectin but similar plasma TNFalpha and leptin levels as compared with OBIR subjects. Genes regulating inflammation (CD68, MCP1, scavenger receptor A, and oxidized LDL receptor 1) were increased by 40%-60% (P < .05) in OBIR vs OBIS cohorts. In addition, genes involved in extracellular matrix formation such as collagen VI and MMP7 were up-regulated by 43% and 78% (P < .05), respectively, in OBIR vs OBIS. The expression of HIF1alpha and VEGF gene expression was increased by 37% and 52%, respectively, in OBIR vs OBIS (P < .01). Despite the differential expression in hypoxia-related genes, adipose tissue oxygenation measured by a Licox oxygen probe was not different between OBIS and OBIR subjects, but it was higher in lean subjects as compared with obese subjects. CONCLUSIONS: We confirmed that adipose tissue inflammation and fibrosis play an important role in the pathogenesis of insulin resistance independent of obesity in humans. Whether hypoxia is simply a consequence of adipose tissue expansion or is related to the pathogenesis of obesity-induced insulin resistance is yet to be understood. PMID- 26871995 TI - Incident Type 2 diabetes and the effect of early regression to normoglycaemia in a population with impaired glucose regulation. AB - AIMS: To report contemporary regression rates from impaired glucose regulation to normal glucose tolerance, identify modifiable factors associated with early regression, and establish whether it affects subsequent diabetes risk in a population-based cohort. METHODS: Participants with impaired glucose regulation (impaired fasting glucose and/or impaired glucose tolerance on a 75-g oral glucose tolerance test) at baseline in the UK-based ADDITION-Leicester study had annual Type 2 diabetes re-screens for 5 years or until diabetes diagnosis. Logistic regression models investigated modifiable risk factors for regression to normal glucose tolerance at 1 year (n = 817). Cox regression models estimated subsequent diabetes risk (n = 630). RESULTS: At 1 year, 54% of participants had regressed to normal glucose tolerance, and 6% had progressed to diabetes. Regression to normal glucose tolerance was associated with weight loss of 0.1-3% [adjusted odds ratio 1.81 (95% CI 1.08, 3.03) compared with maintaining or gaining weight] and a waist circumference reduction of > 3 cm [adjusted odds ratio 1.78 (95% CI 1.03, 3.06) compared with maintaining or increasing waist circumference]. Those with normal glucose tolerance at 1 year subsequently had lower diabetes risk than those who remained with impaired glucose regulation [adjusted hazard ratio 0.19 (95% CI 0.10, 0.37)]. CONCLUSIONS: Early regression to normal glucose tolerance was associated with reduced diabetes incidence, and might be induced by small reductions in weight or waist circumference. If confirmed in experimental research, this could be a clear and achievable target for individuals diagnosed with impaired glucose regulation. PMID- 26871996 TI - Arsenic trioxide-based therapy is suitable for patients with psoriasis-associated acute promyelocytic leukemia - A retrospective clinical study. AB - OBJECTIVE: Many patients with psoriasis have developed acute promyelocytic leukemia (APL) whereas few reports on psoriasis-associated APL were found in the published literature. This study was aimed to study the etiology, clinical characteristics, and prognosis of psoriasis-associated APL and to map a suitable treatment regime for this condition. METHODS: This study retrospectively analyzed the clinical data of 17 patients with psoriasis-associated APL diagnosed and treated in our hospital in the past decade. RESULTS: The 17 patients accounted for 8.3% of the total patients diagnosed with de novo APL during the same period in our hospital. Their clinical characteristics of APL were similar to those of general APL. Four patients had a definite history of taking bimolane. All patients received arsenic trioxide (ATO)-based remission induction and postremission treatment. After induction, 15 patients (88%) achieved hematologic complete remission. With a median follow-up of 27 months, the 3-year estimates of overall survival were 77.2% +/- 12.4% and the 3-year estimates of event-free survival were 70.6% +/- 13.5%. In addition, the ATO-based remission induction and postremission treatment significantly improved psoriasis symptoms in 83 and 85.7% of patients, respectively. Through the final follow-up, no chronic arsenicosis or secondary malignancy was observed. CONCLUSIONS: Psoriasis patients are at high risk for APL. The increased risk is most likely associated with the genetic background and bimolane treatment. The ATO-based therapy is especially suitable for patients with psoriasis-associated APL. Our study also brings a new treatment option for psoriasis. PMID- 26871997 TI - Justice and Surgical Innovation: The Case of Robotic Prostatectomy. AB - Surgical innovation promises improvements in healthcare, but it also raises ethical issues including risks of harm to patients, conflicts of interest and increased injustice in access to health care. In this article, we focus on risks of injustice, and use a case study of robotic prostatectomy to identify features of surgical innovation that risk introducing or exacerbating injustices. Interpreting justice as encompassing matters of both efficiency and equity, we first examine questions relating to government decisions about whether to publicly fund access to innovative treatments. Here the case of robotic prostatectomy exemplifies the difficulty of accommodating healthcare priorities such as improving the health of marginalized groups. It also illustrates challenges with estimating the likely long-term costs and benefits of a new intervention, the difficulty of comparing outcomes of an innovative treatment to those of established treatments, and the further complexity associated with patient and surgeon preferences. Once the decision has been made to fund a new procedure, separate issues of justice arise at the level of providing care to individual patients. Here, the case of robotic prostatectomy exemplifies how features of surgical innovation, such as surgeon learning curves and the need for an adequate volume of cases at a treatment centre, can exacerbate injustices associated with treatment cost and the logistics of travelling for treatment. Drawing on our analysis, we conclude by making a number of recommendations for the just introduction of surgical innovations. PMID- 26871998 TI - Obstructive Sleep Apnea Is Not Associated with Higher Health Care Use after Colonoscopy under Conscious Sedation. AB - RATIONALE: The use of sedation allows medical procedures to be performed outside the operating room while ensuring patient comfort and a controlled environment to increase the yield of the procedure. There is concern about a higher risk of adverse events with use of sedation in patients with obstructive sleep apnea. OBJECTIVES: We aimed to determine if the presence of obstructive sleep apnea increased the risk of hospitalization and/or health care use after patients received moderate conscious sedation for an elective, ambulatory colonoscopy. METHODS: We conducted a retrospective case-control database and chart review study. We compared hospital admissions, intensive care unit (ICU) admissions, and emergency room visits at 24 hours, 7 days, and 30 days in patients with obstructive sleep apnea (n = 3,860) and without obstructive sleep apnea (n = 2,374) who had undergone an elective, ambulatory colonoscopy with sedation. MEASUREMENTS AND MAIN RESULTS: We found no significant differences in hospital admissions, ICU admissions, or emergency room visits between the two groups at any time point within the 30 days following the procedures. In a sensitivity analysis in which we compared 827 individuals with polysomnographically confirmed sleep apnea with control subjects, there was still no difference in hospital admissions, ICU admissions, or emergency room visits in the 30 days after receiving sedation for the procedure. Outcomes were not different in individuals with various severities of obstructive sleep apnea. CONCLUSIONS: The presence of obstructive sleep apnea was not associated with increased early hospital admissions, ICU admissions, or emergency room visits after colonoscopy with sedation. PMID- 26871999 TI - Perceptions of the Cause, Impact and Management of Persistent Fatigue in Patients with Rheumatoid Arthritis Following Tumour Necrosing Factor Inhibition Therapy. AB - INTRODUCTION: Fatigue is a major symptom of rheumatoid arthritis (RA), the most common chronic inflammatory joint disease. The present study explored patients' experiences of RA fatigue to elucidate unique elements and management strategies. METHODS: This single site study recruited tumour necrosis factor-alpha inhibitor (TNFi)-treated RA patients with a moderate/good response in disease activity and persistent moderate/greater fatigue on a five-point verbal rating scale. This qualitative descriptive design used semi-structured questions, individual interviews and content analysis of narrative data. RESULTS: Ten patients were interviewed (six women), with age and disease duration ranges of 44-75 and 6-36 years, respectively. Perceptions of the RA fatigue experience generated four categories (experiencing a distinct, yet seldom discussed RA symptom; seeking an explanation for fatigue; being in an incapacitating state; and trying to manage) and eight subcategories. Fatigue was newly identified as a distinct part of the entity of RA. While patients proposed many plausible root causes, the only rational explanation for the nature of this fatigue was that it was integral to their RA. Singularly, fatigue contributed considerably to RA-imposed lifestyle restrictions. Patients had learnt to accommodate and self-manage fatigue in the absence of professional input. Novel management strategies proposed included patients talking about the nature of RA fatigue with others and the need for staff to alert patients to this distinct symptom of RA. CONCLUSION: Fatigue, branded as a distinct symptom of RA, exerted an identifiable impact on patients. Fatigue is potentially amenable to modification; talking about fatigue was proposed as a novel management strategy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26872000 TI - Effect of High-Intensity Interval Versus Continuous Exercise Training on Functional Capacity and Quality of Life in Patients With Coronary Artery Disease: A RANDOMIZED CLINICAL TRIAL. AB - PURPOSE: There is strong evidence that exercise training has beneficial health effects in patients with cardiovascular disease. Most studies have focused on moderate continuous training (MCT); however, a body of evidence has begun to emerge demonstrating that high-intensity interval training (HIIT) has significantly better results in terms of morbidity and mortality. The aim of this study was to compare the effects of MCT versus HIIT on functional capacity and quality of life and to assess safety. METHODS: Seventy-two patients with ischemic heart disease were assigned to either HIIT or MCT for 8 weeks. We analyzed cardiopulmonary exercise test data, quality of life, and adverse events. RESULTS: High-intensity interval training resulted in a significantly greater increase in (Equation is included in full-text article.)O2peak (4.5 +/- 4.7 mL.kg.min) compared with MCT (2.5 +/- 3.6 mL.kg.min) (P < .05). The aerobic threshold (VT1) increased by 21% in HIIT and 14% in MCT. Furthermore, there was a significant (P < .05) increase in the distance covered in the 6-minute walk distance test in the HIIT group (49.6 +/- 6.3 m) when compared with the MCT group (29.6 +/- 12.0 m). Both training protocols improved quality of life. No adverse events were reported in either of the groups. CONCLUSIONS: On the basis of the results of this study, HIIT should be considered for use in cardiac rehabilitation as it resulted in a greater increase in functional capacity compared with MCT. We also observed greater improvement in quality of life without any increase in cardiovascular risk. PMID- 26872001 TI - Responsive Copolymer Brushes of Poly[(2-(Methacryloyloxy)Ethyl) Trimethylammonium Chloride] (PMETAC) and Poly((1)H,(1)H,(2)H,(2)H-Perfluorodecyl acrylate) (PPFDA) to Modulate Surface Wetting Properties. AB - Polymer brushes have a large potential for controlling properties such as surface lubrication or wetting through facile functionalization. Polymer chemistry, chain density, and length impact on the wetting properties of brushes. This study explores the use of diblock copolymer brushes with different block length and spatial arrangement of the blocks to tune surface wettability. Block copolymer brushes of the polyelectrolyte [2-(methacryloyloxy)ethyl] trimethylammonium chloride (PMETAC) with a contact angle of 17 degrees and a hydrophobic block of (1)H, (1)H, (2)H, (2)H-perfluorodecyl Acrylate (PPFDA) with a contact angle of 130 degrees are synthesized by RAFT polymerization. By changing the sequence of polymerization either block is synthesized as top or bottom block. By varying the concentration of initiator the length of the blocks is varied. Contact angle values with intermediate values between 17 degrees and 130 degrees are measured. In addition, by changing solvent pH and in presence of a different salt the contact angle of the copolymer brushes can be fine tuned. Brushes are characterized by atomic force microscopy, Raman confocal microscopy, and X-ray photoelectron spectroscopy. PMID- 26872002 TI - In sickness and in health: classmates are highly motivated to provide in-hospital support during childhood cancer therapy. AB - OBJECTIVES: Extended hospitalization for school-aged cancer patients increases their risk of social marginalization. School-aged children mature through peer interaction, but healthcare providers fail to incorporate this in rehabilitation efforts. The RESPECT study offers classmates to cancer patients to become ambassadors during hospital stays. This study explores classmate decision-making patterns about ambassadorship. METHODS: An open-ended question was prospectively and consecutively provided to classmates (N = 221) (and parents) of 10 children diagnosed with cancer in 2014 and enrolled in the RESPECT study. Statements were analysed using thematic content analysis. RESULTS: Of 221 classmates, 140 responded (63%). Of these, 81 applied for ambassadorship (median 8/patient), 58 declined, one was undecided. Nine forms were incomplete; leaving 131 in total that revealed 303 statements for analysis. Five major themes emerged: existing friendship (132/303 statements), personal resources (academic, emotional and social) (107/303), attitudes towards the ambassadorship (34/303), hospital environment (18/303) and logistics (12/303). Of the classmates with pre-existing friendships, 77% applied for ambassadorship and 80% with a surplus of personal resources applied. These were predominant predictors for ambassadorship application. Classmate motives were condensed into four archetypes: pre-existing friendship with a surplus of resources (100% applied), non-friend classmates with a surplus of resources (63% applied), pre-existing friendship with limited resources (22% applied) and non-friend classmates with limited resources (0% applied). CONCLUSION: Classmates are highly motivated to support patients during serious illness, irrespective of pre-existing friendships. Ambassadors offer a novel in-hospital approach to promote rehabilitation in children with severe/chronic diseases. Results need validation in other settings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26872003 TI - Dielectric relaxation properties of carboxylic acid-terminated n-alkyl monolayers tethered to Si(1 1 1): dynamics of dipoles and gauche defects. AB - Molecular-level insights into the organization and dynamics of n-alkyl monolayers covalently bonded to Si(1 1 1) were gained from admittance measurements of dipolar relaxation in rectifying Hg|| HOOC-C10H(25-n) Si junctions performed as a function of applied voltage and temperature. A collective behavior of dipole dynamics is inferred from the non-Debye asymmetric relaxation peak shape and strong coupling of the dipole relaxation path with some bending vibrations of the n-alkyl OML (multi-excitation entropy model). A variety of relaxation mechanisms is observed in the frequency range (0.1 Hz-10 MHz) with different dependence of relaxation frequency and dipolar strength on measurement temperature and applied voltage. Their microscopic origin is discussed by comparing the activation energy of relaxation frequency with previous molecular mechanics calculations of saddle point energy barriers for structural defects such as gauche conformations or chain kinks in n-alkanes assemblies. Gauche conformations organized in pairs (kinks) have vanishing relaxation strength below an order-disorder transition temperature T(D) = 175 K and their probability strongly increases with applied reverse voltage, above T(D). The presence of hydrogen bonds between terminal carboxylic acid functionalities is inferred from a comparison with a similar junction bearing a low density of carboxylic acid end groups. This temperature dependent hydrogen-bond network provides some additional stiffness against external electrostatic stress, as deduced from the rather weak sensitivity of relaxation frequencies to applied bias voltage. PMID- 26872004 TI - Multicolor multiphoton microscopy based on a nanosecond supercontinuum laser source. AB - Multicolor multiphoton microscopy is experimentally demonstrated for the first time on a spectral bandwidth of excitation of 300 nm (full width half maximum) thanks to the implementation a nanosecond supercontinuum (SC) source compact and simple with a low repetition rate. The interest of such a wide spectral bandwidth, never demonstrated until now, is highlighted in vivo: images of glioma tumor cells stably expressing eGFP grafted on the brain of a mouse and its blood vessels network labelled with Texas Red((r)) are obtained. These two fluorophores have a spectral bandwidth covering the whole 300 nm available. In parallel, a similar image quality is obtained on a sample of mouse muscle in vitro when excited with this nanosecond SC source or with a classical high rate, femtosecond and quasi monochromatic laser. This opens the way for (i) a simple and very complete biological characterization never performed to date with multiphoton processes, (ii) multiple means of contrast in nonlinear imaging allowed by the use of numerous fluorophores and (iii) other multiphoton processes like three photon ones. PMID- 26872005 TI - Predictors of adherence to a 12-week exercise program among men treated for prostate cancer: ENGAGE study. AB - Understanding the factors that influence adherence to exercise programs is necessary to develop effective interventions for people with cancer. We examined the predictors of adherence to a supervised exercise program for participants in the ENGAGE study - a cluster randomized controlled trial that assessed the efficacy of a clinician-referred 12-week exercise program among men treated for prostate cancer. Demographic, clinical, behavioral, and psychosocial data from 52 participants in the intervention group were collected at baseline through self report and medical records. Adherence to the supervised exercise program was assessed through objective attendance records. Adherence to the supervised exercise program was 80.3%. In the univariate analyses, cancer-specific quality of life subscales (role functioning r = 0.37, P = 0.01; sexual activity r = 0.26, P = 0.06; fatigue r = -0.26, P = 0.06, and hormonal symptoms r = -0.31, P = 0.03) and education (d = -0.60, P = 0.011) were associated with adherence. In the subsequent multivariate analysis, role functioning (B = 0.309, P = 0.019) and hormonal symptoms (B = -0.483, P = 0.054) independently predicted adherence. Men who experienced more severe hormonal symptoms had lower levels of adherence to the exercise program. Those who experienced more positive perceptions of their ability to perform daily tasks and leisure activities had higher levels of adherence to the exercise program. Hormonal symptoms and role functioning need to be considered when conducting exercise programs for men who have been treated for prostate cancer. PMID- 26872007 TI - The effect of Toll-like receptor 4 on beta2-glycoprotein I-induced B cell activation in mouse model. AB - Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human beta2-glycoprotein I (beta2GPI). However, the roles of TLR4 in the activation of B cells and production of anti-beta2GPI antibodies in vivo have been rarely studied. This study aimed to investigate the activation of B cells from TLR4-defective (C3H/HeJ) and TLR4-intact (C3H/HeN) mice pre immunized with human beta2GPI. After beta2GPI injection, the level of anti beta2GPI antibody in the serum of TLR4-defective and TLR4-intact mice was gradually increased and the number and size of germinal centers in the spleen were also significantly increased. Compared with C3H/HeJ mice, we observed significantly higher anti-beta2GPI antibody titer and more germinal centers in C3H/HeN mice. Moreover, the beta2GPI-induced expression of CD40L, CD40, CD80, CD86 and MHC II in C3H/HeN mice was significantly higher than that in C3H/HeJ mice. Furthermore, the beta2GPI-induced expression of B cell activating factor (BAFF) in the spleen and IL-6 and IL-10 in B cells from C3H/HeN mice was also significantly increased compared to C3H/HeJ mice. Taken together, our results suggest that TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with beta2GPI, but the immunological mechanisms of antiphospholipid syndrome (APS) need further investigation. PMID- 26872008 TI - Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer. AB - BACKGROUND: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. METHODS: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. RESULTS: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. CONCLUSIONS: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation. PMID- 26872009 TI - Lynch Syndrome Screening in the Gynecologic Tract: Current State of the Art. AB - Lynch syndrome underlies approximately 5% of endometrial cancers and ~1% of ovarian cancers. Gynecologic malignancies are often the presenting cancer in these patients. Therefore, there is considerable benefit to identifying these patients and enrolling them and affected family members in surveillance programs for secondary malignancies. The molecular basis for Lynch syndrome is a defect in the DNA mismatch repair (MMR) system. Tumors can be screened for these defects using immunohistochemistry to identify loss of MMR proteins or by enlisting polymerase chain reaction to identify the microsatellite instability that attends dysfunctional MMR. However, diagnostic confirmation of Lynch syndrome requires germline mutational testing. The algorithm for screening endometrial carcinomas for Lynch syndrome remains a subject of debate, with some studies supporting universal screening and others proposing a hybrid approach informed by clinicopathologic features. This review discusses the rationales and relative merits of current Lynch syndrome-screening approaches for endometrial and ovarian cancers and provides pathologists with an informed approach to Lynch syndrome testing in gynecologic cancers. It also addresses the clinical difficulties presented by cases with discordant screening and germline results (Lynch-like cancers) and emphasizes the critical role of strong communication with clinician and genetic counseling colleagues to ensure that the significance of a positive screening test is appropriately conveyed to patients. Finally, it discusses the need for more nuanced cost-effective analyses and the potential role for next generation sequencing panels in future screening efforts. PMID- 26872010 TI - Primary and Metastatic Cutaneous Melanomas Express ALK Through Alternative Transcriptional Initiation. AB - A number of common driver mutations have been identified in melanoma, but other genetic or epigenetic aberrations are also likely to play a role in the pathogenesis of melanoma and present potential therapeutic targets. Translocations of the anaplastic lymphoma kinase (ALK), for example, have been reported in spitzoid melanocytic neoplasms leading to kinase-fusion proteins that result in immunohistochemically detectable ALK expression. In this study, we sought to determine whether ALK was also expressed in nonspitzoid primary and metastatic cutaneous melanomas. ALK immunohistochemistry was performed on 603 melanomas (303 primary and 300 metastatic tumors) from 600 patients. ALK immunohistochemistry expression was identified in 7 primary and 9 metastatic tumors. In 5 of 7 primary tumors and in 6 of 9 metastatic lesions, the majority of tumor cells were immunoreactive for ALK. In the other 2 primary and 3 metastatic lesions, positive staining was identified in less than half of the tumor cells. ALK positivity was found in the presence or absence of BRAF or NRAS mutations. In contrast to prior observations with ALK-positive Spitz tumors, none of the ALK-positive melanomas harbored a translocation. Instead, the ALK-positive melanomas predominantly expressed the recently described ALK isoform, ALK, which lacks the extracellular and transmembrane domains of wild-type ALK, consists primarily of the intracellular tyrosine kinase domain, and originates from an alternative transcriptional initiation site within the ALK gene. The findings are clinically relevant as patients with metastatic melanoma who have ALK expression may potentially benefit from treatment with ALK kinase inhibitors. PMID- 26872012 TI - Primary Pseudomyogenic Hemangioendothelioma of Bone. AB - Pseudomyogenic hemangioendothelioma (PMH) is a well-recognized neoplasm that usually arises in the soft tissue; concurrent bone involvement occurs in 24% of cases. PMH of bone without soft tissue involvement is rare. We describe the clinicopathologic findings of 10 such cases, the largest series reported to date. The study included 9 male and 1 female patient; their ages ranged from 12 to 74 years (mean 36.7 y). All patients had multiple tumors with a distinct regional distribution: 45% restricted to the lower extremity; 25% to the spine and pelvis; and 15% to the upper extremity. On imaging studies the tumors were well circumscribed and lytic. The neoplasms were composed of spindled cells arranged in intersecting fascicles with scattered epithelioid cells; epithelioid cells predominated in 3 cases. The neoplastic cells contained abundant densely eosinophilic cytoplasm and vesicular nuclei. There was limited cytologic atypia and necrosis, few mitoses (0 to 2/10 high-power fields), and inconspicuous stroma. Unique findings included abundant intratumoral reactive woven bone and hemorrhage with numerous osteoclast-like giant cells. Immunohistochemically, most tumors were positive for keratin, ERG, and CD31; CD34 was negative. The balanced t(7:19)(q22;13) translocation was documented in 3 cases. Follow-up is limited, but no patient developed documented visceral dissemination, and all have stable or progressive osseous disease. PMH exclusively involving bone is rare. It is multicentric, often involves the lower extremity, and has unusual morphology. The differential diagnosis includes epithelioid vascular neoplasms, giant cell tumor, bone forming neoplasms, and metastatic carcinoma. Because of its rarity, unusual presentation, and morphology, accurate diagnosis can be challenging. PMID- 26872011 TI - Frequent HRAS Mutations in Malignant Ectomesenchymoma: Overlapping Genetic Abnormalities With Embryonal Rhabdomyosarcoma. AB - Malignant ectomesenchymoma (MEM) is an exceedingly rare pediatric sarcoma with a predilection for infants and young children and is composed of dual malignant mesenchymal and neuroectodermal components. Microscopically, MEM displays areas of rhabdomyosarcoma (RMS) with intermixed neuronal/neuroblastic foci. The molecular alterations associated with MEM and its relationship with embryonal RMS (ERMS) and malignant peripheral nerve sheath tumor (MPNST) have not yet been elucidated. In this study we used whole-transcriptome sequencing in 2 MEM index cases with available frozen tissue, followed by screening of the identified genetic abnormalities in 5 additional cases. No candidate fusion genes were detected by FusionSeq analysis; however, the mutation detection algorithms revealed HRAS and PTPRD hotspot mutations in both index cases, with 1 case harboring an additional FBXW7 mutation. As these mutation profiles have been previously described in ERMS we have tested their incidence in a control group of 7 age-matched ERMS. In addition, the gene signature of MEM was compared with that of RMS, MPNST, and neuronal lineage. All 7 MEM patients were male, with a mean age of 7.5 months (range, 0.6 to 17 mo). All except 1 occurred in the pelvic/urogenital region. Most cases showed ERMS elements, with occasional spindle or undifferentiated/round cell areas. The intermixed neuroectodermal components were mostly scattered ganglion cells, ganglioneuroma, or ganglioneuroblastoma. By Sanger sequencing, 6 of 7 (86%) MEMs had HRAS mutations, with no additional case harboring PTPRD or FBXW7 mutations. The only case lacking HRAS mutation showed neuroblastic micronodules without ganglion cells. The trimethylation at lysine 27 of histone H3 (H3K27me3) expression, typically lost in MPNST, was retained in all cases. In the control ERMS group, 5 of 7 (71%) showed RAS mutations, equally distributed among NRAS, KRAS, and HRAS genes. The expression profiling of MEM showed upregulation of skeletal muscle and neuronal genes, with no significant overlap with MPNST. Our results of common HRAS mutations and composite gene signature with RMS and neuronal/neuroblastic elements suggest a closer genetic link of MEM to RMS rather than to MPNST. PMID- 26872014 TI - MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma. AB - BACKGROUND/AIMS: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). METHODS: Quantitative real-time PCR was used to detect the expression miR 361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR 361-5p in vivo. RESULTS: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. CONCLUSION: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients. PMID- 26872015 TI - Hormonal Eligibility Criteria for 'Includes Females' Competition: A Practical but Problematic Solution. AB - The International Association of Athletics Federations (IAAF) and the International Olympic Committee (IOC) adopted testosterone level criteria for eligibility (i.e. 10 nmol/l or 290 ng/dl in blood for IAAF, levels 'within the male range' for IOC) to compete in the 'includes females' category. The policies address the assertion that women with very high endogenous testosterone (unless they are androgen-resistant) have an unfair advantage over women with lower natural levels. Recently, the Court of Arbitration for Sport suspended the 'hyperandrogenism regulation' by the IAAF, but added: 'since there are separate categories of male and female competition, it is necessary for the IAAF to formulate a basis for the division of athletes into male and female categories for the benefit of the broad class of female athletes. The basis chosen should be necessary, reasonable and proportionate to the legitimate objective being pursued' [Branch J: Dutee Chand, Female Sprinter with High Testosterone Level, Wins Right to Compete. The New York Times, July 27, 2015]. An analysis of available evidence below - scientific as well as experiential - suggests that androgen-based criteria can, in fact, be rationally defended as the best currently available and practical approach to determine eligibility for competition in the 'includes females' category. However, to justify such policies, the IOC and IAAF must also show them to be not only rational, but also fair, necessary, and consistent with the treatment of athletes with other endogenous non-physiologic advantages. PMID- 26872013 TI - Prognostic Factors of Hepatosplenic T-cell Lymphoma: Clinicopathologic Study of 28 Cases. AB - Hepatosplenic T-cell lymphoma (HSTCL) is a rare type of lymphoma. Patients have a poor prognosis, and there is no standard of care. We evaluated 28 HSTCL patients to determine factors that may be associated with outcome. There were 19 men and 9 women with a median age of 32.5 years. Most patients had massive splenomegaly, and bone marrow showed sinusoidal involvement by lymphoma. The HSTCL cells expressed gammadelta T-cell receptor (TCR) in 20 (74%), alphabeta TCR in 5 (19%), and neither in 2 (7%) patients (1 case not assessed). Conventional cytogenetics and/or fluorescence in situ hybridization analysis in 24 patients at diagnosis showed isochromosome 7q (i7q) in 10 (42%) and trisomy 8 in 8 (33%) patients. Median overall survival (OS) and event-free survival (EFS) were each 28.3 months. Serum bilirubin level >=1.5 mg/dL, alphabeta TCR expression, and trisomy 8 each correlated significantly with shorter OS and EFS. Patients with HSTCL received a variety of chemotherapy regimens with no regimen better than any other. However, patients who underwent stem cell transplant showed longer survival (OS: hazard ratio 0.3, P=0.09; EFS: hazard ratio 0.2, P=0.034). In conclusion, although HSTCL patients have a poor prognosis overall, the data presented support the novel suggestions that HSTCL patients can be stratified into 2 prognostic groups, with an elevated serum bilirubin level, alphabeta TCR expression, and trisomy 8 identifying a poorer prognostic group. In addition, the outcomes of this patient cohort suggest that stem cell transplantation has value for the treatment of patients with HSTCL. PMID- 26872016 TI - Compensatory Increase of Transglutaminase 2 Is Responsible for Resistance to mTOR Inhibitor Treatment. AB - The mechanistic target of rapamycin complex 1 (mTORC1) plays a crucial role in controlling cell growth and homeostasis. Deregulation of mTOR signaling is frequently observed in some cancers, making it an attractive drug target for cancer therapy. Although mTORC1 inhibitor rapalog-based therapy has shown positive results in various pre-clinical animal cancer studies, tumors rebound upon treatment discontinuation. Moreover, several recent clinical trials showed that the mTORC1 inhibitors rapamycin and rapalog only reduce the capacity for cell proliferation without promoting cell death, consistent with the concept that rapamycin is cytostatic and reduces disease progression but is not cytotoxic. It is imperative that rapamycin-regulated events and additional targets for more effective drug combinations be identified. Here, we report that rapamycin treatment promotes a compensatory increase in transglutaminase 2 (TGM2) levels in mTORC1-driven tumors. TGM2 inhibition potently sensitizes mTORC1-hyperactive cancer cells to rapamycin treatment, and a rapamycin-induced autophagy blockade inhibits the compensatory TGM2 upregulation. More importantly, tumor regression was observed in MCF-7-xenograft tumor-bearing mice treated with both mTORC1 and TGM2 inhibitors compared with those treated with either a single inhibitor or the vehicle control. These results demonstrate a critical role for the compensatory increase in transglutaminase 2 levels in promoting mTORC1 inhibitor resistance and suggest that rational combination therapy may potentially suppress cancer therapy resistance. PMID- 26872017 TI - The Association between Belgian Older Adults' Physical Functioning and Physical Activity: What Is the Moderating Role of the Physical Environment? AB - BACKGROUND: Better physical functioning in the elderly may be associated with higher physical activity levels. Since older adults spend a substantial part of the day in their residential neighborhood, the neighborhood physical environment may moderate associations between functioning and older adults' physical activity. The present study investigated the moderating role of the objective and perceived physical environment on associations between Belgian older adults' physical functioning and transport walking, recreational walking, and moderate-to vigorous physical activity. METHODS: Data from 438 older adults were included. Objective physical functioning was assessed using the Short Physical Performance Battery. Potential moderators included objective neighborhood walkability and perceptions of land use mix diversity, access to recreational facilities, access to services, street connectivity, physical barriers for walking, aesthetics, crime-related safety, traffic speeding-related safety, and walking infrastructure. Transport and recreational walking were self-reported, moderate to-vigorous physical activity was assessed through accelerometers. Multi-level regression analyses were conducted using MLwiN to examine two-way interactions between functioning and the environment on both walking outcomes. Based on a previous study where environment x neighborhood income associations were found for Belgian older adults' moderate-to-vigorous physical activity, three-way functioning x environment x income interactions were examined for moderate-to vigorous physical activity. RESULTS: Objectively-measured walkability moderated the association between functioning and transport walking; this positive association was only present in high-walkable neighborhoods. Moreover, a three way interaction was observed for moderate-to-vigorous physical activity. Only in high-income, high-walkable neighborhoods, there was a positive association between functioning and moderate-to-vigorous physical activity. No functioning x walkability interactions were observed for recreational walking, and none of the perceived environmental variables moderated the positive association between physical functioning and the physical activity outcomes. CONCLUSIONS: For older adults with better physical functioning, living in a high-walkable neighborhood could be beneficial to engage in more transport walking. Living in high-income, high-walkable neighborhoods and having better functioning might also be beneficial for more engagement in moderate-to-vigorous physical activity. This might suggest a protective role of neighborhood walkability for preventing declining physical functioning and consequently decreasing physical activity levels in older adults. However, given the cross-sectional design of the present study, this suggestion needs to be confirmed through longitudinal assessment investigating over-time changes in the observed associations. PMID- 26872018 TI - Can Intrapartum Cardiotocography Predict Uterine Rupture among Women with Prior Caesarean Delivery?: A Population Based Case-Control Study. AB - OBJECTIVE: To compare cardiotocographic abnormalities recorded during labour in women with prior caesarean delivery (CD) and complete uterine rupture with those recorded in controls with prior CD without uterine rupture. STUDY DESIGN: Women with complete uterine rupture during labour between 1997 and 2008 were identified in the Danish Medical Birth Registry (n = 181). Cases were validated by review of medical records and 53 cases with prior CD, trial of labour, available cardiotocogram (CTG) and complete uterine rupture were included and compared with 43 controls with prior CD, trial of labour and available CTG. The CTG tracings were assessed by 19 independent experts divided into groups of three different experts for each tracing. The assessors were blinded to group, outcome and clinical data. They analyzed occurrence of defined abnormalities and classified the traces as normal, suspicious, pathological or pre-terminal according to international guidelines (FIGO). RESULTS: A pathological CTG during the first stage of labour was present in 77% of cases and in 53% of the controls (OR 2.58 [CI: 0.96-6.94] P = 0.066). Fetal tachycardia was more frequent in cases with uterine rupture (OR 2.50 [CI: 1.0-6.26] P = 0.053). Significantly more cases showed more than 10 severe variable decelerations compared with controls (OR 22 [CI: 1.54-314.2] P = 0.022). Uterine tachysystole was not correlated with the presence of uterine rupture. CONCLUSION: A pathological cardiotocogram should lead to particular attention on threatening uterine rupture but cannot be considered a strong predictor as it is common in all women with trial of labour after caesarean delivery. PMID- 26872019 TI - Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin Induced Allergic Airway Inflammation in a Mouse Model. AB - BACKGROUND: Recently, academic studies suggest that global growth of airway allergic disease has a close association with dietary changes including reduced consumption of fiber. Therefore, appropriate dietary fiber supplementation might be potential to prevent airway allergic disease (AAD). OBJECTIVE: We investigated whether dietary fiber intake suppressed the induction of AAD and tried to elucidate the possible underlying mechanisms. METHODS: The control mice and AAD model mice fed with 4% standard-fiber chow, while low-fiber group of mice fed with a 1.75% low-fiber chow. The two fiber-intervened groups including mice, apart from a standard-fiber diet, were also intragastric (i.g.) administrated daily with poorly fermentable cellulose or readily fermentable pectin (0.4% of daily body weight), respectively. All animals except normal mice were sensitized and challenged with ovalbumin (OVA) to induce airway allergic inflammation. Hallmarks of AAD were examined by histological analysis and ELISA. The variation in intestinal bacterial composition was assessed by qualitative analysis of 16S ribosomal DNA (rDNA) content in fecal samples using real-time PCR. RESULTS: Low fiber diet aggravated inflammatory response in ovalbumin-induced allergic mice, whereas dietary fiber intake significantly suppressed the allergic responses, attenuated allergic symptoms of nasal rubbing and sneezing, decreased the pathology of eosinophil infiltration and goblet cell metaplasia in the nasal mucosa and lung, inhibited serum OVA-specific IgE levels, and lowered the levels of Th2 cytokines in NALF and BALF, but, increased Th1 (IFN-gamma) cytokines. Additionally, dietary fiber intake also increased the proportion of Bacteroidetes and Actinobacteria, and decreased Firmicutes and Proteobacteria. Levels of probiotic bacteria, such as Lactobacillus and Bifidobacterium, were upgraded significantly. CONCLUSION: Long-term deficiency of dietary fiber intake increases the susceptibility to AAD, whereas proper fiber supplementation promotes effectively the balance of Th1/Th2 immunity and then attenuates allergic inflammatory responses significantly, as well as optimizes the structure of intestinal microbiota, which suggests potential for novel preventive and therapeutic intervention. PMID- 26872021 TI - Association of MMP-9 Gene Polymorphisms with Glaucoma: A Meta-Analysis. AB - The aim of this study was to evaluate the associations between matrix metalloproteinase-9 (MMP-9) gene polymorphisms (rs17576 and rs3918249) and glaucoma risk. All eligible studies were searched in PubMed, Embase, the Cochrane Library and the China Knowledge Resource Integrated Database. Pooled odds ratios and 95% confidence intervals were used to assess associations between MMP-9 gene polymorphisms and glaucoma. Seven studies on rs17576 (1,357 cases and 1,432 controls) and 3 studies on rs3918249 (550 cases and 794 controls) were included. The results suggest that rs17576 was not associated with glaucoma risk based on current publications. However, stratification analyses indicated that GG genotypes increased the risk of primary open-angle glaucoma in a recessive model (GG vs. AA + AG). The rs3918249 polymorphism was also associated with a decreased risk of glaucoma, especially for Caucasian patients. To sum up, our data indicate that rs17576 polymorphism is not related to glaucoma and rs3918249 polymorphism might be a protective factor against glaucoma. PMID- 26872022 TI - Added Qualifications in Microsurgery: Consideration for Subspecialty Certification in Microvascular Surgery in Europe. AB - Background While implementation of subspecializations may increase expertise in a certain area of treatment, there also exist downsides. Aim of this study was, across several disciplines, to find out if the technique of microsurgery warrants the introduction of a "Certificate of Added Qualifications (CAQ) in microsurgery." Methods An anonymous, web-based survey was administered to directors of microsurgical departments in Europe (n = 205). Respondents were asked, among other questions, whether they had completed a 12-month microvascular surgery fellowship and whether they believed a CAQ in microvascular surgery should be instituted. Results The response rate was 57%, and 33% of the respondents had completed a 12-month microvascular surgery fellowship.A total of 61% of all surgeons supported a CAQ in microsurgery. Answers ranged from 47% of support to 100% of support, depending on the countries surveyed. Discussion This is one of the few reports to evaluate the potential role of subspecialty certification of microvascular surgery across several European countries. The data demonstrate that the majority of directors of microsurgical departments support such a certificate. There was significantly greater support for a CAQ in microsurgery among those who have completed a formal microvascular surgery fellowship themselves. Conclusion This study supports the notion that further discussion and consideration of subspecialty certification in microvascular surgery appears necessary. There are multiple concerns surrounding this issue. Similar to the evolution of hand surgery certification, an exploratory committee of executive members of the respective medical boards and official societies may be warranted. PMID- 26872020 TI - Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury. AB - Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1beta, TNF-alpha and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID- 26872024 TI - A Simple, Visually Oriented Communication System to Improve Postoperative Care Following Microvascular Free Tissue Transfer: Development, Results, and Implications. AB - Background Communication, particularly transmission of information between the surgical and nursing teams, has been identified as one of the most crucial determinants of patient outcomes. Nonetheless, transfer of information among and between the physician and nursing teams in the immediate postoperative period is often informal, verbal, and inconsistent. Methods An iterative process of multidisciplinary information gathering was undertaken to create a novel postoperative communication system (the "Pop-form"). Once developed, nurses were surveyed on multiple measures regarding the perceived likelihood that it would improve their ability to provide directed patient care. Data were quantified using a Likert scale (0-10), and statistically analyzed. Results The Pop-form records and transfers operative details, specific anatomic monitoring parameters, and senior physician contact information. Sixty-eight nurses completed surveys. The perceived usefulness of different components of the Pop-form system was as follows: 8.9 for the description of the procedure; 9.3 for the operative diagram; 9.4 for the monitoring details and parameters; and 9.4 for the direct contact information for the appropriate surgical team member. All respondents were in favor of widespread adoption of the Pop-form. Conclusion This uniform, visual communication system requires less than 1 minute to compose, yet formalizes and standardizes inter-team communication, and therefore shows promise for improving outcomes following microvascular free tissue transfer. We believe that this simple, innovative communication tool has the potential to be more broadly applied to many other health care settings. PMID- 26872023 TI - Successful Salvage of Late Anastomotic Thrombosis after Free Tissue Transfer. AB - Background Anastomotic thrombosis following free tissue transfer (FTT) on or after day 5 ("late thrombosis") is reported to have extremely low rates of salvage. Analysis of our institution's experience with FTT was performed to make recommendations about the optimal management of late thrombosis, and to identify any variables that are correlated with increased salvage rates. Methods The study included patients who underwent FTT between 1986 and 2014, then suffered anastomotic thrombosis on or after postoperative day 5. Twenty-six variables involving demographic information, flap characteristics, circumstances of the thrombotic event, and details of any salvage attempt were analyzed. Patients whose FTT were successfully salvaged and those whose were not were statistically compared. Results Of the 3,212 patients who underwent FTT, 23 suffered late thrombosis (0.7%), and the salvage rate was 60.8% (14 of 23). The salvage rate for reconstruction of the head and neck was 53.3%, breast was 66.7%, and extremity was 100%. There was a statistically significantly greater salvage rate in flaps performed after 1998 than in those performed before 1998 (p = 0.023). There was a nonstatistically significant trend toward increased salvage rates in patients who had no anastomotic thrombotic risk factors, reconstruction using fasciocutaneous flaps, and anastomotic revision using new recipient vessels. Conclusion Our data demonstrate that flap survival after episodes of late thrombosis can be higher than what the literature has previously reported. This underscores the importance of rigorous postoperative monitoring, as well as the importance of exploration at the earliest instance of concern for threatened flap viability. PMID- 26872025 TI - The Early Years of Practice: An Assessment of Operative Efficiency and Cost of Free Flap and Implant Breast Reconstruction at an Academic Institution. AB - Objective The purpose of this study was to evaluate the short-term costs, and financial implications of improvements in operative efficiency of free flap and implant-based breast reconstruction within an academic practice. Methods The billing records of 162 patients who underwent postmastectomy implant-based or free flap breast reconstruction by two newly hired microsurgeons at an academic institution during the 2011, 2012, and 2013 fiscal years were reviewed. Actual data on professional revenue, relative value units (RVUs), and facility costs for the first stage of reconstruction as well as costs of postoperative complications were assessed. Results Free flaps consistently generated more revenue and RVUs than implants (p < 0.001). Rates of major complications and associated costs were greater for free flaps during the first 2 years of practice; however, by the 3rd year rates were similar between free flaps and implants (14.3 vs. 18.2%, p = 0.72). There was a 26% reduction in free flap operative time in 2013 as compared with 2011. Operative efficiency (hourly RVU) of first stage procedures increased each year for both modalities. At the completion of reconstruction, flaps and implants had comparable hourly reimbursement ($1,053 vs. $947, p = 0.72) and hourly RVU (22 vs. 29, p = 0.06). Conclusions Contrary to perceptions that free flap breast reconstructions are financially inefficient for the surgeon, we have found that these complex reconstructive procedures are profitable. Even in the early years of practice, hourly reimbursements from completed flap reconstructions are similar to reimbursements received from similar staged implant reconstructions. PMID- 26872026 TI - The Use of Vascularized Fascia as Carrier in Cases of Prelaminated Fasciocartilaginous and Osseofascial Flaps. AB - Background This experimental study investigates the use of vascularized fascia as carrier for prelaminated cartilage and bone flaps. Methods A total of 30 male New Zealand white rabbits were divided into two equal groups (A and B). The fascia surrounding the inguinal fat and superficial inferior epigastric vessels was dissected. In group A, the fascia was wrapped around a template (20 * 40 mm) of cartilage harvested from the rabbit's ear. In group B, the fascia was wrapped around a 15 * 35 mm piece of rib cortical bone. After a maturation period of 4 weeks, group A was subdivided into three groups (A1, A2, and A3). In group A1 (six animals) the animals were sacrificed and the flaps were sent for histological examination, in A2 (six animals) the flaps were rotated 180 degrees and anchored at knee level, and in A3 (two animals) the flaps were transferred as free flaps to the right SIE (superficial inferior epigastric vessels). The animals of subgroups A2 and A3 were sacrificed after another maturation period of 2 weeks and the flaps were sent for histological examination. After a maturation period of 6 weeks, group B was subdivided into three subgroups (B1, B2, and B3) corresponding to the cartilage subgroups. Subgroups B2 and B3 were sacrificed after 2 weeks. Results All flaps of groups A and B demonstrated good viability apart from one specimen of subgroup B2. Angiogenesis was present in all groups. Conclusion Meticulously dissected vascularized fascia can be successfully used for prelamination of complex fasciocartilaginous or osseofascial flaps. The required maturation periods are 4 and 6 weeks, respectively. PMID- 26872027 TI - Effects of Bezafibrate on the Survival of Random Skin Flaps in Rats. AB - Background Bezafibrate is widely used in clinics for its comparable angiogenic effect. Our research is to investigate the effect of bezafibrate on random skin flap survival. Materials and Methods The "McFarlane flap" rat models were established in 30 male Sprague-Dawley rats which were divided into two groups. The treatment group was given bezafibrate (400 mg/kg/day; gavage administration), and the control group received the vehicle. The flap surviving area was measured after 7 days, and the tissue samples were taken for histological analysis and edema measurement. Vascular endothelial growth factor (VEGF) was determined using immunohistochemical methods. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined with kits. Results Seven days after the operation, the surviving area in the treatment group was larger than in the control group (p < 0.01). The expression of VEGF was increased in the treatment group compared with that in the control group. And the activity of SOD was lower in the treatment group compared with those in the control group (p < 0.01). However, tissue edema, inflammatory cell infiltration, and MDA level were markedly lower in the treatment group than those in the control group (p < 0.01). Conclusion Bezafibrate improves the survival of random skin flaps effectively. PMID- 26872028 TI - Neurological Deficits before and after Surgical Resection of Schwannomas in the Upper Extremities. AB - Background Schwannomas are the most common primary solitary tumor among peripheral nerve sheath tumors. The occurrence of transient or permanent neurological deficits after schwannoma resection is more common than previously recognized. Here, the neurological deficits before and after surgical resection of schwannomas in the upper extremities were examined. Methods The study included 43 upper-extremity schwannomas that were treated surgically between January 2000 and July 2013. The neurological status of each patient (such as pain, sensory disturbances, and motor disturbances) was evaluated preoperatively, immediately postoperatively, and at the final postoperative follow-up. Results Out of the 43 cases, 34 cases exhibited neurological symptoms before the operation, and in 31 of the 34 cases, neurological symptoms were either reduced or disappeared after the surgery. In 20 of the 43 cases, new neurological deficits that had not been observed preoperatively were noted immediately postoperatively; the newly acquired neurological deficits disappeared over time in 5 of the 20 cases. Significantly, more newly acquired neurological deficits remained in cases where the tumor was located in the upper arm and elbow than in cases where the tumor was located in the distal forearm. Conclusion New neurological deficits occurred after surgery in about half of the cases. This ratio was higher than expected, suggesting that schwannoma resection is not always a complication-free operation. Therefore, patients should be informed preoperatively about the possibility of neurological deficits. Furthermore, extreme care should be taken not to damage the affected and uninvolved nerves during surgery. PMID- 26872029 TI - D-Alanylation of Teichoic Acids and Loss of Poly-N-Acetyl Glucosamine in Staphylococcus aureus during Exponential Growth Phase Enhance IL-12 Production in Murine Dendritic Cells. AB - Staphylococcus aureus is a major human pathogen that has evolved very efficient immune evading strategies leading to persistent colonization. During different stages of growth, S. aureus express various surface molecules, which may affect the immune stimulating properties, but very little is known about their role in immune stimulation and evasion. Depending on the growth phase, S. aureus may affect antigen presenting cells differently. Here, the impact of growth phases and the surface molecules lipoteichoic acid, peptidoglycan and poly-N-acetyl glucosamine on the induction of IL-12 imperative for an efficient clearance of S. aureus was studied in dendritic cells (DCs). Exponential phase (EP) S. aureus was superior to stationary phase (SP) bacteria in induction of IL-12, which required actin-mediated endocytosis and endosomal acidification. Moreover, addition of staphylococcal cell wall derived peptidoglycan to EP S. aureus stimulated cells increased bacterial uptake but abrogated IL-12 induction, while addition of lipoteichoic acid increased IL-12 production but had no effect on the bacterial uptake. Depletion of the capability to produce poly-N-acetyl glucosamine increased the IL-12 inducing activity of EP bacteria. Furthermore, the mutant dltA unable to produce D-alanylated teichoic acids failed to induce IL-12 but like peptidoglycan and the toll-like receptor (TLR) ligands LPS and Pam3CSK4 the mutant stimulated increased macropinocytosis. In conclusion, the IL-12 response by DCs against S. aureus is highly growth phase dependent, relies on cell wall D alanylation, endocytosis and subsequent endosomal degradation, and is abrogated by receptor induced macropinocytosis. PMID- 26872031 TI - Resistance to Bacillus thuringiensis Mediated by an ABC Transporter Mutation Increases Susceptibility to Toxins from Other Bacteria in an Invasive Insect. AB - Evolution of pest resistance reduces the efficacy of insecticidal proteins from the gram-positive bacterium Bacillus thuringiensis (Bt) used widely in sprays and transgenic crops. Recent efforts to delay pest adaptation to Bt crops focus primarily on combinations of two or more Bt toxins that kill the same pest, but this approach is often compromised because resistance to one Bt toxin causes cross-resistance to others. Thus, integration of Bt toxins with alternative controls that do not exhibit such cross-resistance is urgently needed. The ideal scenario of negative cross-resistance, where selection for resistance to a Bt toxin increases susceptibility to alternative controls, has been elusive. Here we discovered that selection of the global crop pest, Helicoverpa armigera, for >1000-fold resistance to Bt toxin Cry1Ac increased susceptibility to abamectin and spineotram, insecticides derived from the soil bacteria Streptomyces avermitilis and Saccharopolyspora spinosa, respectively. Resistance to Cry1Ac did not affect susceptibility to the cyclodiene, organophospate, or pyrethroid insecticides tested. Whereas previous work demonstrated that the resistance to Cry1Ac in the strain analyzed here is conferred by a mutation disrupting an ATP binding cassette protein named ABCC2, the new results show that increased susceptibility to abamectin is genetically linked with the same mutation. Moreover, RNAi silencing of HaABCC2 not only decreased susceptibility to Cry1Ac, it also increased susceptibility to abamectin. The mutation disrupting ABCC2 reduced removal of abamectin in live larvae and in transfected Hi5 cells. The results imply that negative cross-resistance occurs because the wild type ABCC2 protein plays a key role in conferring susceptibility to Cry1Ac and in decreasing susceptibility to abamectin. The negative cross-resistance between a Bt toxin and other bacterial insecticides reported here may facilitate more sustainable pest control. PMID- 26872030 TI - The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9. AB - microRNAs are a novel set of small, non-protein-coding nucleotide RNAs that negatively regulate the expression of target mRNAs. miRNA-21 is a microRNA that is highly enriched in endothelial cells. miRNA-21 has been shown to be a potential pro-angiogenic factor in some biological systems. Our previous study showed that the expression of miRNA-21 was up-regulated after spinal cord injury. However, the effect of miRNA-21 on angiogenesis in the spinal cord was unclear. In this study, to understand the role of miRNA-21 on injured endothelial cells exclusively, an oxygen and glucose deprivation model of endothelial cells was constructed, and the up-regulation of miRNA-21 was discovered in this model. An increased level of miRNA-21 by mimics promoted the survival, migration and tube formation of endothelial cells, which simultaneously inhibited tissue inhibitor of metalloproteinase-3 (TIMP3) expression and promoted matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) expression and secretion. A decreased level of miRNA-21 by antagomir exerted an opposite effect. As is well known, survival, migration and tube formation of endothelial cells are necessary prerequisites for angiogenesis after injury. TIMP3 was validated as a direct target of miRNA-21 by dual-luciferase reporter assay. Silencing with small interfering RNA against TIMP3 promoted tube formation and increased MMP2 and MMP9 expression at the protein level. In vivo, we found that decreased levels of miRNA 21 inhibited angiogenesis after spinal cord injury in rats using synchrotron radiation micro-computed tomography. In summary, these findings suggest that miRNA-21 has a protective effect on angiogenesis by reducing cell death and promoting cell survival, migration and tube formation via partially targeting the TIMP3 by potentially regulating MMP2 and MMP9. TIMP3 is a functional target gene. Identifying the role of miRNA-21 in the protection of angiogenesis might offer a novel therapeutic target for secondary spinal cord injury, in which angiogenesis is indispensable. PMID- 26872032 TI - High-Throughput Sequencing Identifies MicroRNAs from Posterior Intestine of Loach (Misgurnus anguillicaudatus) and Their Response to Intestinal Air-Breathing Inhibition. AB - MicroRNAs (miRNAs) exert important roles in animal growth, immunity, and development, and regulate gene expression at the post-transcriptional level. Knowledges about the diversities of miRNAs and their roles in accessory air breathing organs (ABOs) of fish remain unknown. In this work, we used high throughput sequencing to identify known and novel miRNAs from the posterior intestine, an important ABO, in loach (Misgurnus anguillicaudatus) under normal and intestinal air-breathing inhibited conditions. A total of 204 known and 84 novel miRNAs were identified, while 47 miRNAs were differentially expressed between the two small RNA libraries (i.e. between the normal and intestinal air breathing inhibited group). Potential miRNA target genes were predicted by combining our transcriptome data of the posterior intestine of the loach under the same conditions, and then annotated using COG, GO, KEGG, Swissprot and Nr databases. The regulatory networks of miRNAs and their target genes were analyzed. The abundances of nine known miRNAs were validated by qRT-PCR. The relative expression profiles of six known miRNAs and their eight corresponding target genes, and two novel potential miRNAs were also detected. Histological characteristics of the posterior intestines in both normal and air-breathing inhibited group were further analyzed. This study contributes to our understanding on the functions and molecular regulatory mechanisms of miRNAs in accessory air-breathing organs of fish. PMID- 26872034 TI - Assertive community treatment (ACT) case managers' professional identities: A focus group study. AB - Assertive community treatment (ACT) case managers provide healthcare services to people with severe and persistent mental illness. These case managers take on generic roles in multidisciplinary teams and provide all-around services in the clients' private homes. This focus group study aimed to gain insight into Danish ACT case managers' professional identity work by examining their discussions of ethical dilemmas and collaboration in their everyday practice. Data were collected during five focus groups at three ACT teams in the North Denmark Region and subjected to discourse analysis emphasizing how identity work was accomplished through talk. The findings indicated that the case managers constructed professional identities by actively positioning themselves and the particular ACT approach in relation to other mental healthcare professionals and clients. They represented themselves as achieving better client-related outcomes by being more assertive and persistent, and as responsible caregivers who provided the help that their clients needed when other services had failed to do so. They depicted their services as being focused on the clients' well-being, and their persistent efforts to establish and sustain interpersonal relationships with clients were an important part of their service. Basic nursing tasks were described as an important part of their everyday work, and even though such tasks were not distinctive for ACT case managers, the representations of their work seemed to give them a sense of worth as professionals and legitimized a unique role in the community mental healthcare services. PMID- 26872033 TI - Pathophysiology of Endometriosis: Role of High Mobility Group Box-1 and Toll-Like Receptor 4 Developing Inflammation in Endometrium. AB - Oxidative stress has been proposed as a potential factor associated with the establishment and progression of endometriosis. Although a few studies have shown possible mechanisms which may play roles in development, progression of endometriosis, few are known in regards of initiation of the disease, especially in the relationship with endometrium. The aim of our study was to investigate whether normal endometrium may be changed by Damage-associated molecular patterns (DAMPs), which may contribute developing pathologic endometrium to induce endometriosis. Endometrial tissues were obtained from 10 patients with fibroids undergoing hysterectomy at a university hospital. High mobility group box-1 (HMGB 1), which is a representative DAMP, has been chosen that may induce alteration in endometrium. In preceding immunohistochemistry experiments using paraffin-block sections from endometriosis (N = 33) and control (N = 27) group, retrospectively, HMGB-1 expression was shown in both epithelial and stromal cell. HMGB-1 expression was significantly increased in secretory phase of endometriosis group, comparing to the controls. To examine the alteration of endometrial stromal cell (HESC) by oxidative stress in terms of HMGB-1, cell proliferation and expression of its receptor, TLR4 was measured according to recombinant HMGB-1 use. Cell proliferation was assessed by CCK-8 assay; real-time PCR and western blotting were used to quantify Toll like receptor 4 (TLR4) mRNA and protein expression respectively. A TLR4 antagonist (LPS-RS) and an inhibitor of the NF-kappaB pathway (TPCA-1, an IKK-2 inhibitor) were used to confirm the relationships between HMGB-1, TLR4, and the NF-kappaB pathway. Passive release of HMGB-1 was significantly proportional to the increase in cell death (P<0.05). HESCs showed significant proliferation following treatment with rHMGB-1 (P<0.05), and increased TLR4 expression was observed following rHMGB-1 treatment (P<0.05) in a concentration-dependent manner. Treatment with a TLR4 antagonist and an NF-kappaB inhibitor resulted in suppression of rHMGB-1-induced HESC proliferation (P<0.05). Levels of IL-6 were significantly decreased following treatment with an NF-kappaB inhibitor (P<0.05). Our results support the development of altered, pathological endometrium resulted from oxidative stress in normal endometrium. These findings may provide important insights into the changes in endometrium linking the development and progression of endometriosis. PMID- 26872035 TI - Alternative Pathway Inhibition by Exogenous Factor H Fails to Attenuate Inflammation and Vascular Leakage in Experimental Pneumococcal Sepsis in Mice. AB - Streptococcus pneumoniae is a common cause of sepsis. Effective complement activation is an important component of host defence against invading pathogens, whilst excessive complement activation has been associated with endothelial dysfunction and organ damage. The alternative pathway amplification loop is important for the enhancement of complement activation. Factor H is a key negative regulator of the alternative pathway amplification loop and contributes to tight control of complement activation. We assessed the effect of inhibition of the alternative pathway on sepsis associated inflammation and disease severity using human factor H treatment in a clinically relevant mice model of pneumococcal sepsis. Mice were infected intravenously with live Streptococcus pneumoniae. At the first clinical signs of infection, 17 hours post-infection, mice were treated with ceftriaxone antibiotic. At the same time purified human factor H or in controls PBS was administered. Treatment with human factor H did not attenuate disease scores, serum pro-inflammatory cytokines, or vascular permeability and did not significantly affect C3 and C3a production at 26 h post infection. Therefore, we conclude that inhibition of the alternative complement pathway by exogenous human factor H fails to attenuate inflammation and vascular leakage at a clinically relevant intervention time point in pneumococcal sepsis in mice. PMID- 26872037 TI - Epidemiology of chronic spontaneous urticaria: results from a nationwide, population-based study in Italy. AB - BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disease, but there is a paucity of precise epidemiological data on this disease. OBJECTIVES: To obtain information on the epidemiology of CSU in Italy. METHODS: The data source was the Health Search IMS Health Longitudinal Patient Database. The study population was formed by patients aged >= 15 years, registered with a total of 700 general practitioners, homogeneously distributed across Italy. An algorithm based on the International Classification of Diseases, ninth revision, Clinical Modification was used for the identification of patients with CSU. The annual prevalence and incidence rates of CSU over a 12-year period (2002-2013) were estimated, along with demographic and clinical determinants. RESULTS: The annual prevalence of CSU ranged from 0.02% in 2002 to 0.38% in 2013. The incidence was 0.10-1.50 per 1000 person-years. For both prevalence and incidence rates, female patients outnumbered male. The risk of CSU was statistically significantly higher in the presence of the following variables: obesity; anxiety, dissociative and somatoform disorders; malignancies; use of immunosuppressive drugs; and chronic use of systemic corticosteroids. History of autoimmune thyroiditis showed a trend towards an increased risk of CSU, though it was not statistically significant. Smoking was associated with a significantly reduced risk of CSU. CONCLUSIONS: Our findings on CSU prevalence are consistent with those obtained in previous studies. Furthermore, this large population-based study provides important information regarding the association of CSU with demographic and clinical determinants, which have been examined in the primary-care setting. PMID- 26872036 TI - FastGGM: An Efficient Algorithm for the Inference of Gaussian Graphical Model in Biological Networks. AB - Biological networks provide additional information for the analysis of human diseases, beyond the traditional analysis that focuses on single variables. Gaussian graphical model (GGM), a probability model that characterizes the conditional dependence structure of a set of random variables by a graph, has wide applications in the analysis of biological networks, such as inferring interaction or comparing differential networks. However, existing approaches are either not statistically rigorous or are inefficient for high-dimensional data that include tens of thousands of variables for making inference. In this study, we propose an efficient algorithm to implement the estimation of GGM and obtain p value and confidence interval for each edge in the graph, based on a recent proposal by Ren et al., 2015. Through simulation studies, we demonstrate that the algorithm is faster by several orders of magnitude than the current implemented algorithm for Ren et al. without losing any accuracy. Then, we apply our algorithm to two real data sets: transcriptomic data from a study of childhood asthma and proteomic data from a study of Alzheimer's disease. We estimate the global gene or protein interaction networks for the disease and healthy samples. The resulting networks reveal interesting interactions and the differential networks between cases and controls show functional relevance to the diseases. In conclusion, we provide a computationally fast algorithm to implement a statistically sound procedure for constructing Gaussian graphical model and making inference with high-dimensional biological data. The algorithm has been implemented in an R package named "FastGGM". PMID- 26872038 TI - Case of metachronous and multifocal extramammary Paget's disease. PMID- 26872039 TI - Coupled RNA-SIP and metatranscriptomics of active chemolithoautotrophic communities at a deep-sea hydrothermal vent. AB - The chemolithoautotrophic microbial community of the rocky subseafloor potentially provides a large amount of organic carbon to the deep ocean, yet our understanding of the activity and metabolic complexity of subseafloor organisms remains poorly described. A combination of metagenomic, metatranscriptomic, and RNA stable isotope probing (RNA-SIP) analyses were used to identify the metabolic potential, expression patterns, and active autotrophic bacteria and archaea and their pathways present in low-temperature hydrothermal fluids from Axial Seamount, an active submarine volcano. Metagenomic and metatranscriptomic results showed the presence of genes and transcripts for sulfur, hydrogen, and ammonium oxidation, oxygen respiration, denitrification, and methanogenesis, as well as multiple carbon fixation pathways. In RNA-SIP experiments across a range of temperatures under reducing conditions, the enriched (13)C fractions showed differences in taxonomic and functional diversity. At 30 degrees C and 55 degrees C, Epsilonproteobacteria were dominant, oxidizing hydrogen and primarily reducing nitrate. Methanogenic archaea were also present at 55 degrees C, and were the only autotrophs present at 80 degrees C. Correspondingly, the predominant CO2 fixation pathways changed from the reductive tricarboxylic acid (rTCA) cycle to the reductive acetyl-CoA pathway with increasing temperature. By coupling RNA-SIP with meta-omics, this study demonstrates the presence and activity of distinct chemolithoautotrophic communities across a thermal gradient of a deep-sea hydrothermal vent. PMID- 26872040 TI - A bacterial filter protects and structures the gut microbiome of an insect. AB - Associations with symbionts within the gut lumen of hosts are particularly prone to disruption due to the constant influx of ingested food and non-symbiotic microbes, yet we know little about how partner fidelity is maintained. Here we describe for the first time the existence of a gut morphological filter capable of protecting an animal gut microbiome from disruption. The proventriculus, a valve located between the crop and midgut of insects, functions as a micro-pore filter in the Sonoran Desert turtle ant (Cephalotes rohweri), blocking the entry of bacteria and particles ?0.2 MUm into the midgut and hindgut while allowing passage of dissolved nutrients. Initial establishment of symbiotic gut bacteria occurs within the first few hours after pupation via oral-rectal trophallaxis, before the proventricular filter develops. Cephalotes ants are remarkable for having maintained a consistent core gut microbiome over evolutionary time and this partner fidelity is likely enabled by the proventricular filtering mechanism. In addition, the structure and function of the cephalotine proventriculus offers a new perspective on organismal resistance to pathogenic microbes, structuring of gut microbial communities, and development and maintenance of host-microbe fidelity both during the animal life cycle and over evolutionary time. PMID- 26872041 TI - Integrated multi-omics analyses reveal the biochemical mechanisms and phylogenetic relevance of anaerobic androgen biodegradation in the environment. AB - Steroid hormones, such as androgens, are common surface-water contaminants. However, literature on the ecophysiological relevance of steroid-degrading organisms in the environment, particularly in anoxic ecosystems, is extremely limited. We previously reported that Steroidobacter denitrificans anaerobically degrades androgens through the 2,3-seco pathway. In this study, the genome of Sdo. denitrificans was completely sequenced. Transcriptomic data revealed gene clusters that were distinctly expressed during anaerobic growth on testosterone. We isolated and characterized the bifunctional 1-testosterone hydratase/dehydrogenase, which is essential for anaerobic degradation of steroid A-ring. Because of apparent substrate preference of this molybdoenzyme, corresponding genes, along with the signature metabolites of the 2,3-seco pathway, were used as biomarkers to investigate androgen biodegradation in the largest sewage treatment plant in Taipei, Taiwan. Androgen metabolite analysis indicated that denitrifying bacteria in anoxic sewage use the 2,3-seco pathway to degrade androgens. Metagenomic analysis and PCR-based functional assays showed androgen degradation in anoxic sewage by Thauera spp. through the action of 1 testosterone hydratase/dehydrogenase. Our integrative 'omics' approach can be used for culture-independent investigations of the microbial degradation of structurally complex compounds where isotope-labeled substrates are not easily available. PMID- 26872042 TI - Novel microbial assemblages inhabiting crustal fluids within mid-ocean ridge flank subsurface basalt. AB - Although little is known regarding microbial life within our planet's rock-hosted deep subseafloor biosphere, boreholes drilled through deep ocean sediment and into the underlying basaltic crust provide invaluable windows of access that have been used previously to document the presence of microorganisms within fluids percolating through the deep ocean crust. In this study, the analysis of 1.7 million small subunit ribosomal RNA genes amplified and sequenced from marine sediment, bottom seawater and basalt-hosted deep subseafloor fluids that span multiple years and locations on the Juan de Fuca Ridge flank was used to quantitatively delineate a subseafloor microbiome comprised of distinct bacteria and archaea. Hot, anoxic crustal fluids tapped by newly installed seafloor sampling observatories at boreholes U1362A and U1362B contained abundant bacterial lineages of phylogenetically unique Nitrospirae, Aminicenantes, Calescamantes and Chloroflexi. Although less abundant, the domain Archaea was dominated by unique, uncultivated lineages of marine benthic group E, the Terrestrial Hot Spring Crenarchaeotic Group, the Bathyarchaeota and relatives of cultivated, sulfate-reducing Archaeoglobi. Consistent with recent geochemical measurements and bioenergetic predictions, the potential importance of methane cycling and sulfate reduction were imprinted within the basalt-hosted deep subseafloor crustal fluid microbial community. This unique window of access to the deep ocean subsurface basement reveals a microbial landscape that exhibits previously undetected spatial heterogeneity. PMID- 26872044 TI - Diagnosis and treatment of obstructive sleep apnea during pregnancy. AB - PURPOSE OF REVIEW: This review aims to provide an update on recent advances in the diagnosis and treatment of obstructive sleep apnea (OSA) during pregnancy and its effect on maternal and fetal outcomes. RECENT FINDINGS: Current OSA screening tools may not perform well in this population. There are some pieces of evidence linking poorer maternal and neonatal outcome with pregnant patients having OSA. At present, there are inadequate data on which to base fetal or maternal parameters for treatment of OSA, and no evidence that treatment in the short-term impacts maternal or neonatal outcomes. SUMMARY: Further research is needed to help in the detection and treatment of OSA in pregnancy. PMID- 26872043 TI - Ubiquitous Gammaproteobacteria dominate dark carbon fixation in coastal sediments. AB - Marine sediments are the largest carbon sink on earth. Nearly half of dark carbon fixation in the oceans occurs in coastal sediments, but the microorganisms responsible are largely unknown. By integrating the 16S rRNA approach, single cell genomics, metagenomics and transcriptomics with (14)C-carbon assimilation experiments, we show that uncultured Gammaproteobacteria account for 70-86% of dark carbon fixation in coastal sediments. First, we surveyed the bacterial 16S rRNA gene diversity of 13 tidal and sublittoral sediments across Europe and Australia to identify ubiquitous core groups of Gammaproteobacteria mainly affiliating with sulfur-oxidizing bacteria. These also accounted for a substantial fraction of the microbial community in anoxic, 490-cm-deep subsurface sediments. We then quantified dark carbon fixation by scintillography of specific microbial populations extracted and flow-sorted from sediments that were short term incubated with (14)C-bicarbonate. We identified three distinct gammaproteobacterial clades covering diversity ranges on family to order level (the Acidiferrobacter, JTB255 and SSr clades) that made up >50% of dark carbon fixation in a tidal sediment. Consistent with these activity measurements, environmental transcripts of sulfur oxidation and carbon fixation genes mainly affiliated with those of sulfur-oxidizing Gammaproteobacteria. The co localization of key genes of sulfur and hydrogen oxidation pathways and their expression in genomes of uncultured Gammaproteobacteria illustrates an unknown metabolic plasticity for sulfur oxidizers in marine sediments. Given their global distribution and high abundance, we propose that a stable assemblage of metabolically flexible Gammaproteobacteria drives important parts of marine carbon and sulfur cycles. PMID- 26872046 TI - Correction: Evasion of Immunity to Plasmodium falciparum: Rosettes of Blood Group A Impair Recognition of PfEMP1. PMID- 26872045 TI - Glycomics and glycoproteomics of membrane proteins and cell-surface receptors: Present trends and future opportunities. AB - Membrane proteins mediate cell-cell interactions and adhesion, the transfer of ions and metabolites, and the transmission of signals from the extracellular environment to the cell interior. The extracellular domains of most cell membrane proteins are glycosylated, often at multiple sites. There is a growing awareness that glycosylation impacts the structure, interaction, and function of membrane proteins. The application of glycoproteomics and glycomics methods to membrane proteins has great potential. However, challenges also arise from the unique physical properties of membrane proteins. Successful analytical workflows must be developed and disseminated to advance functional glycoproteomics and glycomics studies of membrane proteins. This review explores the opportunities and challenges related to glycomic and glycoproteomic analysis of membrane proteins, including discussion of sample preparation, enrichment, and MS/MS analyses, with a focus on recent successful workflows for analysis of N- and O-linked glycosylation of mammalian membrane proteins. PMID- 26872048 TI - Assessment of genetic fidelity and composition: Mixed elicitors enhance triterpenoid and flavonoid biosynthesis of Glycyrrhiza uralensis Fisch. tissue cultures. AB - Glycyrrhiza uralensis has acquired significant importance due to its medicinal properties and health function. In this study, the quality of G. uralensis adventitious roots was evaluated in terms of genetic stability, active compounds, and anti-inflammatory activity. Monomorphic banding pattern obtained from the mother plant and tissue cultures of G. uralensis with randomly amplified polymorphic DNA markers confirmed the genetic stability of adventitious roots. Neoliquiritin (neoisoliquiritin), ononin, liquiritin, and glycyrrhizic acid were identified from G. uralensis adventitious roots on the basis of high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. This study also revealed that adventitious roots possessed a better anti inflammatory effect than native roots. To increase the contents of G. uralensis active components, elicitors were used in the adventitious roots culture. The combination of methyl jasmonate and phenylalanine synergistically stimulated the accumulation of glycyrrhetinic acid (0.22 mg/g) and total flavonoid (5.43 mg/g) compared with single treatment. In conclusion, G. uralensis adventitious roots can be an exploitable system for the production of licorice. PMID- 26872049 TI - Hydrogen Bond Basicity Prediction for Medicinal Chemistry Design. AB - Hydrogen bonding is discussed in the context of medicinal chemistry design. Minimized molecular electrostatic potential (Vmin) is shown to be an effective predictor of hydrogen bond basicity (pKBHX), and predictive models are presented for a number of hydrogen bond acceptor types relevant to medicinal chemistry. The problems posed by the presence of nonequivalent hydrogen bond acceptor sites in molecular structures are addressed by using nonlinear regression to fit measured pKBHX to calculated Vmin. Predictions are made for hydrogen bond basicity of fluorine in situations where relevant experimental measurements are not available. It is shown how predicted pKBHX can be used to provide insight into the nature of bioisosterism and to profile heterocycles. Examples of pKBHX prediction for molecular structures with multiple, nonequivalent hydrogen bond acceptors are presented. PMID- 26872047 TI - Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome. AB - Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. AIMS: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL. PMID- 26872050 TI - Focus Group Study Exploring Factors Related to Frequent Sickness Absence. AB - INTRODUCTION: Research investigating frequent sickness absence (3 or more episodes per year) is scarce and qualitative research from the perspective of frequent absentees themselves is lacking. The aim of the current study is to explore awareness, determinants of and solutions to frequent sickness absence from the perspective of frequent absentees themselves. METHODS: We performed a qualitative study of 3 focus group discussions involving a total of 15 frequent absentees. Focus group discussions were audiotaped and transcribed verbatim. Results were analyzed with the Graneheim method using the Job Demands Resources (JD-R) model as theoretical framework. RESULTS: Many participants were not aware of their frequent sickness absence and the risk of future long-term sickness absence. As determinants, participants mentioned job demands, job resources, home demands, poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Managing these factors and improving communication (skills) were regarded as solutions to reduce frequent sickness absence. CONCLUSIONS: The JD-R model provided a framework for determinants of and solutions to frequent sickness absence. Additional determinants were poor health, chronic illness, unhealthy lifestyles, and diminished feeling of responsibility to attend work in cases of low job resources. Frequent sickness absence should be regarded as a signal that something is wrong. Managers, supervisors, and occupational health care providers should advise and support frequent absentees to accommodate job demands, increase both job and personal resources, and improve health rather than express disapproval of frequent sickness absence and apply pressure regarding work attendance. PMID- 26872052 TI - Sequential process in brain-derived neurotrophic factor-induced functional periodontal tissue regeneration. AB - We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin alphaVbeta3, and integrin alpha2beta1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration. PMID- 26872051 TI - Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin. AB - BACKGROUND: Light fractionation significantly increases the efficacy of 5 aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. RESULTS: In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. DISCUSSION: The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy. PMID- 26872053 TI - Interaction of the Heparin-Binding Consensus Sequence of beta-Amyloid Peptides with Heparin and Heparin-Derived Oligosaccharides. AB - Alzheimer's disease (AD) is characterized by the presence of amyloid plaques in the AD brain. Comprised primarily of the 40- and 42-residue beta-amyloid (Abeta) peptides, there is evidence that the heparan sulfate (HS) of heparan sulfate proteoglycans (HSPGs) plays a role in amyloid plaque formation and stability; however, details of the interaction of Abeta peptides with HS are not known. We have characterized the interaction of heparin and heparin-derived oligosaccharides with a model peptide for the heparin- and HS-binding domain of Abeta peptides (Ac-VHHQKLV-NH2; Abeta(12-18)), with mutants of Abeta(12-18), and with additional histidine-containing peptides. The nature of the binding interaction was characterized by NMR, binding constants and other thermodynamic parameters were determined by isothermal titration calorimetry (ITC), and relative binding affinities were determined by heparin affinity chromatography. The binding of Abeta(12-18) by heparin and heparin-derived oligosaccharides is pH dependent, with the imidazolium groups of the histidine side chains interacting site-specifically within a cleft created by a trisaccharide sequence of heparin, the binding is mediated by electrostatic interactions, and there is a significant entropic contribution to the binding free energy as a result of displacement of Na(+) ions from heparin upon binding of cationic Abeta(12-18). The binding constant decreases as the size of the heparin-derived oligosaccharide decreases and as the concentration of Na(+) ion in the bulk solution increases. Structure binding relationships characterized in this study are analyzed and discussed in terms of the counterion condensation theory of the binding of cationic peptides by anionic polyelectrolytes. PMID- 26872055 TI - In Vitro Longitudinal Relaxivity Profile of Gd(ABE-DTTA), an Investigational Magnetic Resonance Imaging Contrast Agent. AB - PURPOSE: MRI contrast agents (CA) whose contrast enhancement remains relatively high even at the higher end of the magnetic field strength range would be desirable. The purpose of this work was to demonstrate such a desired magnetic field dependency of the longitudinal relaxivity for an experimental MRI CA, Gd(ABE-DTTA). MATERIALS AND METHODS: The relaxivity of 0.5mM and 1mM Gd(ABE-DTTA) was measured by Nuclear Magnetic Relaxation Dispersion (NMRD) in the range of 0.0002 to 1T. Two MRI and five NMR instruments were used to cover the range between 1.5 to 20T. Parallel measurement of a Gd-DTPA sample was performed throughout as reference. All measurements were carried out at 37 degrees C and pH 7.4. RESULTS: The relaxivity values of 0.5mM and 1mM Gd(ABE-DTTA) measured at 1.5, 3, and 7T, within the presently clinically relevant magnetic field range, were 15.3, 11.8, 12.4 s-1mM-1 and 18.1, 16.7, and 13.5 s-1mM-1, respectively. The control 4 mM Gd-DTPA relaxivities at the same magnetic fields were 3.6, 3.3, and 3.0 s-1mM-1, respectively. CONCLUSIONS: The longitudinal relaxivity of Gd(ABE DTTA) measured within the presently clinically relevant field range is three to five times higher than that of most commercially available agents. Thus, Gd(ABE DTTA) could be a practical choice at any field strength currently used in clinical imaging including those at the higher end. PMID- 26872054 TI - Th17 Pathway As a Target for Multipotent Stromal Cell Therapy in Dogs: Implications for Translational Research. AB - Detrimental Th17 driven inflammatory and autoimmune disease such as Crohn's disease, graft versus host disease and multiple sclerosis remain a significant cause of morbidity and mortality worldwide. Multipotent stromal/stem cell (MSC) inhibit Th17 polarization and activation in vitro and in rodent models. As such, MSC based therapeutic approaches are being investigated as novel therapeutic approaches to treat Th17 driven diseases in humans. The significance of naturally occurring diseases in dogs is increasingly recognized as a realistic platform to conduct pre-clinical testing of novel therapeutics. Full characterization of Th17 cells in dogs has not been completed. We have developed and validated a flow cytometric method to detect Th17 cells in canine blood. We further demonstrate that Th17 and other IL17 producing cells are present in tissues of dogs with naturally occurring chronic inflammatory diseases. Finally, we have determined the kinetics of a canine specific Th17 polarization in vitro and demonstrate that canine MSC inhibit Th17 polarization in vitro, in a PGE2 independent mechanism. Our findings provide fundamental research tools and suggest that naturally occurring diseases in dogs, such as inflammatory bowel disease, may be harnessed to translate novel MSC based therapeutic strategies that target the Th17 pathway. PMID- 26872056 TI - OncoBinder facilitates interpretation of proteomic interaction data by capturing coactivation pairs in cancer. AB - High-throughput methods such as co-immunoprecipitationmass spectrometry (coIP-MS) and yeast 2 hybridization (Y2H) have suggested a broad range of unannotated protein-protein interactions (PPIs), and interpretation of these PPIs remains a challenging task. The advancements in cancer genomic researches allow for the inference of "coactivation pairs" in cancer, which may facilitate the identification of PPIs involved in cancer. Here we present OncoBinder as a tool for the assessment of proteomic interaction data based on the functional synergy of oncoproteins in cancer. This decision tree-based method combines gene mutation, copy number and mRNA expression information to infer the functional status of protein-coding genes. We applied OncoBinder to evaluate the potential binders of EGFR and ERK2 proteins based on the gastric cancer dataset of The Cancer Genome Atlas (TCGA). As a result, OncoBinder identified high confidence interactions (annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) or validated by low-throughput assays) more efficiently than co-expression based method. Taken together, our results suggest that evaluation of gene functional synergy in cancer may facilitate the interpretation of proteomic interaction data. The OncoBinder toolbox for Matlab is freely accessible online. PMID- 26872057 TI - The molecular and clinical verification of therapeutic resistance via the p38 MAPK-Hsp27 axis in lung cancer. AB - Treatment failure followed by relapse and metastasis in patients with non-small cell lung cancer is often the result of acquired resistance to cisplatin-based chemotherapy. A cancer stem cell (CSC)-mediated anti-apoptotic phenomenon is responsible for the development of drug resistance. The underlying molecular mechanism related to cisplatin resistance is still controversial, and a new strategy is needed to counteract cisplatin resistance. We used a nonadhesive culture system to generate drug-resistant spheres (DRSPs) derived from cisplatin resistant H23 lung cancer cells. The expressions of drug-resistance genes, properties of CSCs, and markers of anti-apoptotic proteins were compared between control cells and DRSPs. DRSPs exhibited upregulation of cisplatin resistance related genes. Gradual morphological alterations showing epithelial-to mesenchymal transition phenomenon and increased invasion and migration abilities were seen during induction of DRSPs. Compared with control cells, DRSPs displayed increased CSC and anti-apoptotic properties, greater resistance to cisplatin, and overexpression of p-Hsp27 via activation of p38 MAPK signaling. Knockdown of Hsp27 or p38 decreased cisplatin resistance and increased apoptosis in DRSPs. Clinical studies confirmed that the expression of p-Hsp27 was closely associated with prognosis. Overexpression of p-Hsp27 was usually detected in advanced-stage patients with lung cancer and indicated short survival. SUMMARY: DRSPs were useful for investigating drug resistance and may provide a practical model for studying the crucial role of p-Hsp27 in the p38 MAPK-Hsp27 axis in CSC-mediated cisplatin resistance. Targeting this axis using siRNA Hsp27 may provide a treatment strategy to improve prognosis and prolong survival in lung cancer patients. PMID- 26872059 TI - Overexpression of TSC-22 (transforming growth factor- beta-stimulated clone-22) causes marked obesity, splenic abnormality and B cell lymphoma in transgenic mice. AB - In this study, we generated transgenic (Tg) mice, which overexpressed transforming growth factor (TGF)-beta stimulated clone-22 (TSC-22), and investigate the functional role of TSC-22 on their development and pathogenesis. We obtained 13 Tg-founders (two mice from C57BL6/J and 11 mice from BDF1). Three of 13 Tg-founders were sterile, and the remaining Tg-founders also could generate only a limited number of the F1 generation. We obtained 32 Tg-F1 mice. Most of the Tg-mice showed marked obesity. Histopathological examination could be performed on 31 Tg-mice; seventeen mice died by some disease in their entire life and 14 mice were killed for examination. Most of the Tg-mice examined showed splenic abnormality, in which marked increase of the megakaryocytes, unclearness of the margin of the red pulp and the white pulp, and the enlargement of the white pulp was observed. B cell lymphoma was developed in 10 (71%) of 14 disease died F1 mice. These results indicate that constitutive over-expression of TSC-22 might disturb the normal embryogenesis and the normal lipid metabolism, and induce the oncogenic differentiation of hematopoietic cells. PMID- 26872058 TI - Age-related reduction of antibody response against the human endogenous retrovirus K envelope in women. AB - In the present study, the correlation between the antibody response against human endogenous retrovirus K (HERV-K) envelope and human age was investigated. Antibody levels were compared in groups in their 20s (n = 25), 30s (n = 39), 40s (n = 68), 50s (n = 32), and 60s and over (n = 25), which included healthy individuals and breast cancer and/or cervical cancer patients. It appeared that both IgM and IgG responses against the HERV-K envelope fell with increasing age. There were no differences in anti-HERV-K envelope antibody levels between healthy individuals and cancer patients. Therefore, our results indicated that the anti HERV-K antibody levels cannot be considered as cancer-specific marker. Also, IgG1 appeared to be the predominant subtype in the reduction of the IgG response by age. Receiver operating characteristic curves of anti-HERV-K envelope IgM levels indicated that the groups of people in their 20s or 30s could be distinguished from those in their 40s, 50s or 60s and over with satisfactory sensitivity and specificity. These findings indicate that the serum antibody level of HERV-K envelope is a critical parameter reflecting person's age. PMID- 26872061 TI - Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis. AB - BACKGROUND AND PURPOSE: The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability. METHODS: In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands, immunoglobulin G index and leukocyte count were investigated. Long-term MS risk and disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite components) were examined in a retrospective cohort of 78 patients with ON as the first demyelinating episode (mean follow-up 14 years). The predictive ability of CHI3L2 was compared with CHI3L1. RESULTS: Cerebrospinal fluid levels of CHI3L2 and chitotriosidase were significantly elevated in patients with ON and were associated with MS risk measures. CHI3L2 levels predicted MS development after ON (hazard ratio 1.95, P = 0.00039, Cox regression) and cognitive impairment by the Paced Auditory Serial Addition Test (P = 0.0357, linear regression) at follow-up. In a multivariate analysis of MS risk, CHI3L2 performed better than CHI3L1. CONCLUSIONS: CHI3L2 and chitotriosidase are promising biomarkers in patients with a first demyelinating episode. Our findings thus support a role for these proteins as biomarkers in early MS. PMID- 26872060 TI - Construction and analysis of cardiac hypertrophy-associated lncRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in cardiac hypertrophy. AB - Cardiac hypertrophy (CH) could increase cardiac after-load and lead to heart failure. Recent studies have suggested that long non-coding RNA (lncRNA) played a crucial role in the process of the cardiac hypertrophy, such as Mhrt, TERMINATOR. Some studies have further found a new interacting mechanism, competitive endogenous RNA (ceRNA), of which lncRNA could interact with micro-RNAs (miRNA) and indirectly interact with mRNAs through competing interactions. However, the mechanism of ceRNA regulated by lncRNA in the CH remained unclear. In our study, we generated a global triple network containing mRNA, miRNA and lncRNA, and extracted a CH related lncRNA-mRNA network (CHLMN) through integrating the data from starbase, miRanda database and gene expression profile. Based on the ceRNA mechanism, we analyzed the characters of CHLMN and found that 3 lncRNAs (SLC26A4 AS1, RP11-344E13.3 and MAGI1-IT1) were high related to CH. We further performed cluster module analysis and random walk with restart for the CHLMN, finally 14 lncRNAs had been discovered as the potential CH related disease genes. Our results showed that lncRNA played an important role in the CH and could shed new light to the understanding underlying mechanisms of the CH. PMID- 26872063 TI - Missense Variant in MAPK Inactivator PTPN5 Is Associated with Decreased Severity of Post-Burn Hypertrophic Scarring. AB - BACKGROUND: Hypertrophic scarring (HTS) is hypothesized to have a genetic mechanism, yet its genetic determinants are largely unknown. The mitogen activated protein kinase (MAPK) pathways are important mediators of inflammatory signaling, and experimental evidence implicates MAPKs in HTS formation. We hypothesized that single-nucleotide polymorphisms (SNPs) in MAPK-pathway genes would be associated with severity of post-burn HTS. METHODS: We analyzed data from a prospective-cohort genome-wide association study of post-burn HTS. We included subjects with deep-partial-thickness burns admitted to our center who provided blood for genotyping and had at least one Vancouver Scar Scale (VSS) assessment. After adjusting for HTS risk factors and population stratification, we tested MAPK-pathway gene SNPs for association with the four VSS variables in a joint regression model. In addition to individual-SNP analysis, we performed gene based association testing. RESULTS: Our study population consisted of 538 adults (median age 40 years) who were predominantly White (76%) males (71%) admitted to our center from 2007-2014 with small-to-moderate-sized burns (median burn size 6% total body surface area). Of 2,146 SNPs tested, a rare missense variant in the PTPN5 gene (rs56234898; minor allele frequency 1.5%) was significantly associated with decreased severity of post-burn HTS (P = 1.3*10-6). In gene-based analysis, PTPN5 (P = 1.2*10-5) showed a significant association and BDNF (P = 9.5*10-4) a borderline-significant association with HTS severity. CONCLUSIONS: We report PTPN5 as a novel genetic locus associated with HTS severity. PTPN5 is a MAPK inhibitor expressed in neurons, suggesting a potential role for neurotrophic factors and neuroinflammatory signaling in HTS pathophysiology. PMID- 26872062 TI - Engineered Promoters for Potent Transient Overexpression. AB - The core promoter, which is generally defined as the region to which RNA Polymerase II is recruited to initiate transcription, plays a pivotal role in the regulation of gene expression. The core promoter consists of different combinations of several short DNA sequences, termed core promoter elements or motifs, which confer specific functional properties to each promoter. Earlier studies that examined the ability to modulate gene expression levels via the core promoter, led to the design of strong synthetic core promoters, which combine different core elements into a single core promoter. Here, we designed a new core promoter, termed super core promoter 3 (SCP3), which combines four core promoter elements (the TATA box, Inr, MTE and DPE) into a single promoter that drives prolonged and potent gene expression. We analyzed the effect of core promoter architecture on the temporal dynamics of reporter gene expression by engineering EGFP expression vectors that are driven by distinct core promoters. We used live cell imaging and flow cytometric analyses in different human cell lines to demonstrate that SCPs, particularly the novel SCP3, drive unusually strong long term EGFP expression. Importantly, this is the first demonstration of long-term expression in transiently transfected mammalian cells, indicating that engineered core promoters can provide a novel non-viral strategy for biotechnological as well as gene-therapy-related applications that require potent expression for extended time periods. PMID- 26872065 TI - Size-Independent Exciton Localization Efficiency in Colloidal CdSe/CdS Core/Crown Nanosheet Type-I Heterostructures. AB - CdSe/CdS core/crown nanoplatelet type I heterostructures are a class of two dimensional materials with atomically precise thickness and many potential optoelectronic applications. It remains unclear how the precise thickness and lack of energy disorder affect the properties of exciton transport in these materials. By steady-state photoluminescence excitation spectroscopy and ultrafast transient absorption spectroscopy, we show that in five CdSe/CdS core/crown structures with the same core and increasing crown size (with thickness of ~1.8 nm, width of ~11 nm, and length from 20 to 40 nm), the crown-to core exciton localization efficiency is independent of crown size and increases with photon energy above the band edge (from 70% at 400 nm to ~100% at 370 nm), while the localization time increases with the crown size. These observations can be understood by a model that accounts for the competition of in-plane exciton diffusion and selective hole trapping at the core/crown interface. Our findings suggest that the exciton localization efficiency can be further improved by reducing interfacial defects. PMID- 26872066 TI - Manifestations of bodily isomerism. AB - We report the findings present in 49 postmortem specimens from patients with so called heterotaxy, concentrating on those found in the extracardiac systems of organs. Also known as bodily isomerism, we suggest that it is important to segregate the syndromes into their isomeric subtypes to be able to make inferences regarding likely extracardiac and intracardiac findings to allow for proper surveillance. We demonstrate that this is best done on the basis of the atrial appendages, which were isomeric in all the hearts obtained from the specimens available for our inspection. The abdominal organs do not demonstrate isomerism, and they show variable features when compared to the isomeric atrial appendages. PMID- 26872064 TI - Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections. AB - The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1-3 distinct haplotypes per infestation. PMID- 26872067 TI - Utilisation of extended release quetiapine (Seroquel XLTM): Results from an observational cohort study in England. AB - BACKGROUND: A post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England. AIM: To present a description of the drug utilisation characteristics of quetiapine XL. METHODS: An observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated. RESULTS: The final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n=3820), MDD (n=2844), schizophrenia (n=2373) and other (non-licensed) indications (n=3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300 mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100mg/day [IQR 50, 300]). CONCLUSIONS: The prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved. PMID- 26872068 TI - Effect of Decompressive Craniectomy on Perihematomal Edema in Patients with Intracerebral Hemorrhage. AB - BACKGROUND: Perihematomal edema contributes to secondary brain injury in the course of intracerebral hemorrhage. The effect of decompressive surgery on perihematomal edema after intracerebral hemorrhage is unknown. This study analyzed the course of PHE in patients who were or were not treated with decompressive craniectomy. METHODS: More than 100 computed tomography images from our published cohort of 25 patients were evaluated retrospectively at two university hospitals in Switzerland. Computed tomography scans covered the time from admission until day 100. Eleven patients were treated by decompressive craniectomy and 14 were treated conservatively. Absolute edema and hematoma volumes were assessed using 3-dimensional volumetric measurements. Relative edema volumes were calculated based on maximal hematoma volume. RESULTS: Absolute perihematomal edema increased from 42.9 ml to 125.6 ml (192.8%) after 21 days in the decompressive craniectomy group, versus 50.4 ml to 67.2 ml (33.3%) in the control group (Delta at day 21 = 58.4 ml, p = 0.031). Peak edema developed on days 25 and 35 in patients with decompressive craniectomy and controls respectively, and it took about 60 days for the edema to decline to baseline in both groups. Eight patients (73%) in the decompressive craniectomy group and 6 patients (43%) in the control group had a good outcome (modified Rankin Scale score 0 to 4) at 6 months (P = 0.23). CONCLUSIONS: Decompressive craniectomy is associated with a significant increase in perihematomal edema compared to patients who have been treated conservatively. Perihematomal edema itself lasts about 60 days if it is not treated, but decompressive craniectomy ameliorates the mass effect exerted by the intracerebral hemorrhage plus the perihematomal edema, as reflected by the reduced midline shift. PMID- 26872070 TI - Palladium-mediated borylation of pentafluorosulfanyl functionalized compounds: the crucial role of metal fluorido complexes. AB - Stoichiometric reactions of SF5 functionalized bromo or iodo aromatics at [Pd(PiPr3)2] (1) led to the oxidative addition products 3, 5 and 7. They were converted into their corresponding palladium fluorido complexes, which reacted readily with bis(pinacolato)diboron (B2pin2) to give the borylated SF5 aromatic compounds. Based on these studies a catalytic borylation of SF5 organyls was developed. PMID- 26872069 TI - UBA5 Mutations Cause a New Form of Autosomal Recessive Cerebellar Ataxia. AB - Autosomal recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders. For many affected patients, the genetic cause remains undetermined. Through whole-exome sequencing, we identified compound heterozygous mutations in ubiquitin-like modifier activating enzyme 5 gene (UBA5) in two Chinese siblings presenting with ARCA. Moreover, copy number variations in UBA5 or ubiquitin-fold modifier 1 gene (UFM1) were documented with the phenotypes of global developmental delays and gait disturbances in the ClinVar database. UBA5 encodes UBA5, the ubiquitin-activating enzyme of UFM1. However, a crucial role for UBA5 in human neurological disease remains to be reported. Our molecular study of UBA5-R246X revealed a dramatically decreased half-life and loss of UFM1 activation due to the absence of the catalytic cysteine Cys250. UBA5-K310E maintained its interaction with UFM1, although with less stability, which may affect the ability of this UBA5 mutant to activate UFM1. Drosophila modeling revealed that UBA5 knockdown induced locomotive defects and a shortened lifespan accompanied by aberrant neuromuscular junctions (NMJs). Strikingly, we found that UFM1 and E2 cofactor knockdown induced markedly similar phenotypes. Wild-type UBA5, but not mutant UBA5, significantly restored neural lesions caused by the absence of UBA5. The finding of a UBA5 mutation in cerebellar ataxia suggests that impairment of the UFM1 pathway may contribute to the neurological phenotypes of ARCA. PMID- 26872071 TI - Oxidation of cefazolin by potassium permanganate: Transformation products and plausible pathways. AB - Cefazolin was demonstrated to exert high reactivity toward permanganate (Mn(VII)), a common oxidant in water pre-oxidation treatment. In this study, five transformation products were found to be classified into three categories according to the contained characteristic functional groups: three (di-)sulfoxide products, one sulfone product and one di-ketone product. Products analyses showed that two kinds of reactions including oxidation of thioether and the cleavage of unsaturated CC double bond occurred during transformation of cefazolin by Mn(VII). Subsequently, the plausible transformation pathways under different pH conditions were proposed based on the identified products and chemical reaction principles. More importantly, the simulation with real surface water matrix indicated that the proposed transformation pathways of cefazolin could be replayed in real water treatment practices. PMID- 26872072 TI - Copper-Catalyzed SN2'-Selective Allylic Substitution Reaction of gem Diborylalkanes. AB - A Cu/(NHC)-catalyzed SN2'-selective substitution reaction of allylic electrophiles with gem-diborylalkanes is reported. Different substituted gem diborylalkanes and allylic electrophiles can be employed in this reaction, and various synthetic valuable functional groups can be tolerated. The asymmetric version of this reaction was initially researched with chiral N-heterocyclic carbene (NHC) ligands. PMID- 26872073 TI - Protective Role of Flavonoids and Lipophilic Compounds from Jatropha platyphylla on the Suppression of Lipopolysaccharide (LPS)-Induced Inflammation in Macrophage Cells. AB - Seventeen polyphenols (e.g, apigenin, genistein, and luteolin glycosides) and 11 lipophilic compounds (e.g., fatty acids, sterols, and terpenes) were detected by LC-MS/MS-ESI and GC-MS, respectively, in Jatropha platyphylla. Extracts from pulp, kernel, and leaves and fractions were studied to know their effect on some pro-inflammatory mediators. Phenolic and lipophilic extracts showed significant inhibitory effects on ROS and NO production while not affecting mitochondrial activity or superoxide generation rate in lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells. In addition, NO production was also diminished by lipophilic leaf fractions F1 and F2 with the latter fraction showing a greater effect and composed mainly of sterols and terpene. Furthermore, total extracts showed nonselective inhibitions against cyclooxygenase COX-1 and COX-2 activities. All together, these results suggest that J. platyphylla extracts have potential in treating inflammatory diseases and their activity is mediated by flavonoids and lipophilic compounds. PMID- 26872074 TI - Infant emotional distress, maternal restriction at a home meal, and child BMI gain through age 6years in the Colorado Adoption Project. AB - Infant temperament and parental feeding practices may be risk factors for childhood obesity, however most studies have relied upon parent-report assessments. We tested whether infant emotional distress and maternal restrictive feeding at 12-months of age, assessed observationally at a home feeding interaction, predicted child BMI through age 6years. We conducted a prospective observational study of 86 children (34 girls and 52 boys, from 55 adoptive and 31 non-adoptive families) enrolled in the Colorado Adoption Project. Mother-infant feeding interactions were video-recorded during a home snack or meal at year 1, and child anthropometrics (length or height, and weight) were assessed at years 1 through 6. The main outcome measures were child weight-for-length at year 1 and body mass index (BMI: kg/m(2)) at years 2-6. Results of generalized linear models indicated that greater infant emotional distress at 12-months predicted greater increases in child weight status through age 6years, B=0.62 and odds ratio (OR)=1.87. In separate analyses, restrictive feeding interacted with child sex in predicting weight status trajectories (p=.012). Male infants whose mothers displayed any compared to no restriction at year 1 showed a downward BMI trajectory from 2 to 6years; for female infants, exposure to any compared to no restriction prompts predicted increasing BMI from 4 to 6years. In sum, early obesity prevention strategies should pay greater attention to infant temperament, especially distress and negative affect, and how parents respond to such cues. Additionally, 'responsive feeding' strategies that provide an alternative to restriction warrant greater research during infancy. PMID- 26872075 TI - Walking the tightrope: proteostasis and neurodegenerative disease. AB - A characteristic of many neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), is the aggregation of specific proteins into protein inclusions and/or plaques in degenerating brains. While much of the aggregated protein consists of disease specific proteins, such as amyloid-beta, alpha-synuclein, or superoxide dismutase1 (SOD1), many other proteins are known to aggregate in these disorders. Although the role of protein aggregates in the pathogenesis of neurodegenerative diseases remains unknown, the ubiquitous association of misfolded and aggregated proteins indicates that significant dysfunction in protein homeostasis (proteostasis) occurs in these diseases. Proteostasis is the concept that the integrity of the proteome is in fine balance and requires proteins in a specific conformation, concentration, and location to be functional. In this review, we discuss the role of specific mechanisms, both inside and outside cells, which maintain proteostasis, including molecular chaperones, protein degradation pathways, and the active formation of inclusions, in neurodegenerative diseases associated with protein aggregation. A characteristic of many neurodegenerative diseases is the aggregation of specific proteins, which alone provides strong evidence that protein homeostasis is disrupted in these disease states. Proteostasis is the maintenance of the proteome in the correct conformation, concentration, and location by functional pathways such as molecular chaperones and protein degradation machinery. Here, we discuss the potential roles of quality control pathways, both inside and outside cells, in the loss of proteostasis during aging and disease. PMID- 26872076 TI - Bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes versus cold-knife transurethral incision for the treatment of posterior urethral stricture: a prospective, randomized study. AB - OBJECTIVE: Evaluate the efficiency and safety of bipolar plasma vaporization using plasma-cutting and plasma-loop electrodes for the treatment of posterior urethral stricture. Compare the outcomes following bipolar plasma vaporization with conventional cold-knife urethrotomy. METHODS: A randomized trial was performed to compare patient outcomes from the bipolar and cold-knife groups. All patients were assessed at 6 and 12 months postoperatively via urethrography and uroflowmetry. At the end of the first postoperative year, ureteroscopy was performed to evaluate the efficacy of the procedure. The mean follow-up time was 13.9 months (range: 12 to 21 months). If re-stenosis was not identified by both urethrography and ureteroscopy, the procedure was considered "successful". RESULTS: Fifty-three male patients with posterior urethral strictures were selected and randomly divided into two groups: bipolar group (n=27) or cold-knife group (n=26). Patients in the bipolar group experienced a shorter operative time compared to the cold-knife group (23.45+/-7.64 hours vs 33.45+/-5.45 hours, respectively). The 12-month postoperative Qmax was faster in the bipolar group than in the cold-knife group (15.54+/-2.78 ml/sec vs 18.25+/-2.12 ml/sec, respectively). In the bipolar group, the recurrence-free rate was 81.5% at a mean follow-up time of 13.9 months. In the cold-knife group, the recurrence-free rate was 53.8%. CONCLUSIONS: The application of bipolar plasma-cutting and plasma-loop electrodes for the management of urethral stricture disease is a safe and reliable method that minimizes the morbidity of urethral stricture resection. The advantages include a lower recurrence rate and shorter operative time compared to the cold-knife technique. PMID- 26872077 TI - Eszopiclone versus zopiclone in the treatment of insomnia. AB - OBJECTIVE: To determine the therapeutic effects of two selective GABA-A agonists, zopiclone and eszopiclone, in the treatment of insomnia. METHODS: This study comprised a phase III, single-center, randomized, double-blind, double-dummy, parallel-group, non-inferiority trial. Patients were randomized to receive zopiclone 7.5 mg or eszopiclone 3 mg, both orally, for four weeks. In total, 199 patients were evaluated during two visits and then followed for at least six weeks. The primary endpoint was the Insomnia Severity Index after four weeks of treatment. Secondary endpoints were obtained through polysomnography data, including total sleep time, sleep latency and sleep efficiency. The frequency of adverse events was also analyzed. ClinicalTrials.gov: NCT01100164. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of eszopiclone over zopiclone. Analysis of objective parameters assessed by polysomnography showed that eszopiclone increased total sleep time and also improved sleep efficiency. The safety profile of both study treatments was similar and the most common events reported in both groups were dysgeusia, headache, dizziness, irritability and nausea. Adverse events were observed in 223 patients, 109 (85.2%) in the eszopiclone group and 114 (87.7%) in the zopiclone group. CONCLUSION: Based on the Insomnia Severity Index at the end of four weeks of treatment, eszopiclone demonstrated efficacy comparable to that of zopiclone in the treatment of insomnia, increasing total sleep time as well as sleep efficiency according to polysomnography. PMID- 26872078 TI - Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer. AB - OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range. PMID- 26872079 TI - Severe potential drug-drug interactions in older adults with dementia and associated factors. AB - OBJECTIVE: To identify the main severe potential drug-drug interactions in older adults with dementia and to examine the factors associated with these interactions. METHOD: This was a cross-sectional study. The enrolled patients were selected from six geriatrics clinics of tertiary care hospitals across Mexico City. The patients had received a clinical diagnosis of dementia based on the current standards and were further divided into the following two groups: those with severe drug-drug interactions (contraindicated/severe) (n=64) and those with non-severe drug-drug interactions (moderate/minor/absent) (n=117). Additional socio-demographic, clinical and caregiver data were included. Potential drug-drug interactions were identified using Micromedex Drug Reax 2.0(r) database. RESULTS: A total of 181 patients were enrolled, including 57 men (31.5%) and 124 women (68.5%) with a mean age of 80.11+/-8.28 years. One hundred and seven (59.1%) patients in our population had potential drug-drug interactions, of which 64 (59.81%) were severe/contraindicated. The main severe potential drug-drug interactions were caused by the combinations citalopram/anti platelet (11.6%), clopidogrel/omeprazole (6.1%), and clopidogrel/aspirin (5.5%). Depression, the use of a higher number of medications, dementia severity and caregiver burden were the most significant factors associated with severe potential drug-drug interactions. CONCLUSIONS: Older people with dementia experience many severe potential drug-drug interactions. Anti-depressants, antiplatelets, anti-psychotics and omeprazole were the drugs most commonly involved in these interactions. Despite their frequent use, anti-dementia drugs were not involved in severe potential drug-drug interactions. The number and type of medications taken, dementia severity and depression in patients in addition to caregiver burden should be considered to avoid possible drug interactions in this population. PMID- 26872080 TI - Six-minute walk test in children and adolescents with renal diseases: tolerance, reproducibility and comparison with healthy subjects. AB - OBJECTIVES: To evaluate exercise tolerance and the reproducibility of the six minute walk test in Brazilian children and adolescents with chronic kidney disease and to compare their functional exercise capacities with reference values for healthy children. METHODS: This cross-sectional study assessed the use of the six-minute walk test in children and adolescents aged 6-16 with stage V chronic kidney disease. For statistical analysis of exercise tolerance, including examinations of correlations and comparisons with reference values, the longest walked distances were considered. The reproducibility of the six-minute walk test was assessed using intraclass correlation coefficients. RESULTS: A total of 38 patients (14 females and 24 males) were evaluated, including 5 on peritoneal dialysis, 12 on hemodialysis and 21 who had undergone renal transplantation, with a median age of 11.2 years (6.5-16). The median walked distance was 538.5 meters (413-685) and the six-minute walk test was found to be reproducible. The walked distance was significantly correlated with age (r=0.66), weight (r=0.76), height (r=0.82), the height Z score (r=0.41), hemoglobin (r=0.46), hematocrit (r=0.47) and post-test systolic blood pressure (r=0.39). The chronic kidney disease patients predicted walked distance was 84.1% of the reference value according to age, 90.6% according to age-corrected height and 87.4% according to a predictive equation. CONCLUSIONS: The stage V chronic kidney disease patients had a significantly decreased functional exercise capacity, as measured by the six minute walk test, compared with the healthy pediatric reference values. In addition, the six-minute walk test was shown to be well tolerated, reliable and applicable as a low-cost tool to monitor functional exercise capacity in patients with renal disease. PMID- 26872081 TI - Endoscopic versus surgical treatment of ampullary adenomas: a systematic review and meta-analysis. AB - The aim of this study is to address the outcomes of endoscopic resection compared with surgery in the treatment of ampullary adenomas. A systematic review and meta analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. For this purpose, the Medline, Embase, Cochrane, Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS), Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were scanned. Studies included patients with ampullary adenomas and data considering endoscopic treatment compared with surgery. The entire analysis was based on a fixed-effects model. Five retrospective cohort studies were selected (466 patients). All five studies (466 patients) had complete primary resection data available and showed a difference that favored surgical treatment (risk difference [RD] = -0.24, 95% confidence interval [CI] = -0.44 to -0.04). Primary success data were identified in all five studies as well. Analysis showed that the surgical approach outperformed endoscopic treatment for this outcome (RD = -0.37, 95% CI = -0.50 to -0.24). Recurrence data were found in all studies (466 patients), with a benefit indicated for surgical treatment (RD = 0.10, 95% CI = -0.01 to 0.19). Three studies (252 patients) presented complication data, but analysis showed no difference between the approaches for this parameter (RD = -0.15, 95% CI = -0.53 to 0.23). Considering complete primary resection, primary success and recurrence outcomes, the surgical approach achieves significantly better results. Regarding complication data, this systematic review concludes that rates are not significantly different. PMID- 26872082 TI - Venous thromboembolism in Latin America: a review and guide to diagnosis and treatment for primary care. AB - There are various region-specific challenges to the diagnosis and effective treatment of venous thromboembolism in Latin America. Clear guidance for physicians and patient education could improve adherence to existing guidelines. This review examines available information on the burden of pulmonary embolism and deep vein thrombosis in Latin America and the regional issues surrounding the diagnosis and treatment of pulmonary embolism and deep vein thrombosis. Potential barriers to appropriate care, as well as treatment options and limitations on their use, are discussed. Finally, an algorithmic approach to the diagnosis and treatment of venous thromboembolism in ambulatory patients is proposed and care pathways for patients with pulmonary embolism and deep vein thrombosis are outlined for primary care providers in Latin America. PMID- 26872085 TI - Preparation of Microvolume Anion-Exchange Cartridge for Inductively Coupled Plasma Mass Spectrometry-Based Determination of (237)Np Content in Spent Nuclear Fuel. AB - Microvolume anion-exchange porous polymer disk-packed cartridges were prepared for Am/Np separation, which is required prior to the measurement of Neptunium-237 ((237)Np) with inductively coupled plasma mass spectrometry (ICPMS). Disks with a volume of 0.08 cm(3) were cut out from porous sheets having anion-exchange-group containing polymer chains densely attached on the pore surface. Four different amine-based groups, N,N-dimethylaminoethyl methacrylate, trimethylammonium, diethylamine, and triethylenediamine (TEDA), were selected as the anion-exchange groups to be introduced into the porous sheets. The separation performances of Am/Np were evaluated using a standard solution of (243)Am, which had the same activity as its daughter nuclide (239)Np in secular equilibrium. (239)Np recovery of close to 100% with practically no contamination of (243)Am was achieved using the TEDA-introduced disk-packed cartridge. The time to elute (239)Np from the cartridge was approximately 40 s. The TEDA-introduced disk-packed cartridge was applied to the separation of Np from a spent nuclear fuel sample to confirm its separation performance. A known amount of (243)Am ((239)Np) was added to the spent nuclear fuel sample solution to monitor the chemical yield of Np. The chemical yield of Np calculated from a measured concentration of (239)Np was 90.4%. Am leakage in the Np-eluted solution was less than 1 ppt, corresponding to 0.001% of the original Am concentration in the sample. This indicates that no additional (239)Np was produced by the decay of the (243)Am remaining in the Np eluted solution, thus providing a reliable chemical yield. U, which can cause a serious spectral interference involving the peak tail from the mass spectrum of (238)U, was thoroughly removed with the TEDA cartridge, providing interference free measurement of (237)Np. The concentration of (237)Np obtained by ICPMS was 718 +/- 12 ng/mg-U, which agrees well with the theoretically calculated value. Compared with the conventional separation technique using commercially available anion-exchange resin columns, the time required to adsorb, wash, and elute Np using the TEDA- introduced disk-packed cartridge was reduced by 75%. PMID- 26872083 TI - Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control. AB - The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: "diabetes kidney disease" and "renal failure" in combination with "diabetes treatment" and "oral antidiabetic drugs" or "oral hypoglycemic agents." The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID- 26872086 TI - Condition for the negative capacitance effect in metal-ferroelectric-insulator semiconductor devices. AB - In this paper, we report a detailed study of the negative capacitance field effect transistor (NCFET). We present the condition for the stabilization of the negative capacitance to achieve the voltage amplification across the active layer. The theory is based on Landau's theory of ferroelectrics combined with the surface potential model in all regimes of operation. We demonstrate the validity of the presented theory on experimental NCFETs using a gate stack made of P(VDF TrFE) and SiO2. The proposed analytical modeling shows good agreement with experimental data. PMID- 26872087 TI - Rhythms and Blues. PMID- 26872084 TI - Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis. AB - OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate. METHODS: Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with 3H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 umol/kg methotrexate, n=7), or commercial methotrexate (0.5 umol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis. RESULTS: The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment. CONCLUSIONS: The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were clearly superior to the effects of a commercial methotrexate preparation. This result is conceivably due to greater methotrexate uptake by the joints when the drug is associated with a nanoemulsion. PMID- 26872088 TI - Global optimization of small bimetallic Pd-Co binary nanoalloy clusters: a genetic algorithm approach at the DFT level. AB - The global optimisation of small bimetallic PdCo binary nanoalloys are systematically investigated using the Birmingham Cluster Genetic Algorithm (BCGA). The effect of size and composition on the structures, stability, magnetic and electronic properties including the binding energies, second finite difference energies and mixing energies of Pd-Co binary nanoalloys are discussed. A detailed analysis of Pd-Co structural motifs and segregation effects is also presented. The maximal mixing energy corresponds to Pd atom compositions for which the number of mixed Pd-Co bonds is maximised. Global minimum clusters are distinguished from transition states by vibrational frequency analysis. HOMO-LUMO gap, electric dipole moment and vibrational frequency analyses are made to enable correlation with future experiments. PMID- 26872090 TI - Comparative Assessment of Female Mouse Model of Graves' Orbitopathy Under Different Environments, Accompanied by Proinflammatory Cytokine and T-Cell Responses to Thyrotropin Hormone Receptor Antigen. AB - We recently described a preclinical model of Graves' orbitopathy (GO), induced by genetic immunization of eukaryotic expression plasmid encoding human TSH receptor (TSHR) A-subunit by muscle electroporation in female BALB/c mice. The onset of orbital pathology is characterized by muscle inflammation, adipogenesis, and fibrosis. Animal models of autoimmunity are influenced by their environmental exposures. This follow-up study was undertaken to investigate the development of experimental GO in 2 different locations, run in parallel under comparable housing conditions. Functional antibodies to TSHR were induced in TSHR A-subunit plasmid-immunized animals, and antibodies to IGF-1 receptor alpha-subunit were also present, whereas control animals were negative in both locations. Splenic T cells from TSHR A-subunit primed animals undergoing GO in both locations showed proliferative responses to purified TSHR antigen and secreted interferon-gamma, IL-10, IL-6, and TNF-alpha cytokines. Histopathological evaluation showed orbital tissue damage in mice undergoing GO, manifest by adipogenesis, fibrosis, and muscle damage with classic signs of myopathy. Although no inflammatory infiltrate was observed in orbital tissue in either location, the appearances were consistent with a "hit-and-run" immune-mediated inflammatory event. A statistically significant increase of cumulative incidence of orbital pathology when compared with control animals was shown for both locations, confirming onset of orbital dysimmune myopathy. Our findings confirm expansion of the model in different environments, accompanied with increased prevalence of T cell-derived proinflammatory cytokines, with relevance for pathogenesis. Wider availability of the model makes it suitable for mechanistic studies into pathogenesis and undertaking of novel therapeutic approaches. PMID- 26872089 TI - Endothelial Estrogen Receptor-alpha Does Not Protect Against Vascular Stiffness Induced by Western Diet in Female Mice. AB - Consumption of a diet high in fat and refined carbohydrates (Western diet [WD]) is associated with obesity and insulin resistance, both major risk factors for cardiovascular disease (CVD). In women, obesity and insulin resistance abrogate the protection against CVD likely afforded by estrogen signaling through estrogen receptor (ER)alpha. Indeed, WD in females results in increased vascular stiffness, which is independently associated with CVD. We tested the hypothesis that loss of ERalpha signaling in the endothelium exacerbates WD-induced vascular stiffening in female mice. We used a novel model of endothelial cell (EC) specific ERalpha knockout (EC-ERalphaKO), obtained after sequential crossing of the ERalpha double floxed mice and VE-Cadherin Cre-recombinase mice. Ten-week-old females, EC-ERalphaKO and aged-matched genopairs were fed either a regular chow diet (control diet) or WD for 8 weeks. Vascular stiffness was measured in vivo by pulse wave velocity and ex vivo in aortic explants by atomic force microscopy. In addition, vascular reactivity was assessed in isolated aortic rings. Initial characterization of the model fed a control diet did not reveal changes in whole body insulin sensitivity, aortic vasoreactivity, or vascular stiffness in the EC ERalphaKO mice. Interestingly, ablation of ERalpha in ECs reduced WD-induced vascular stiffness and improved endothelial-dependent dilation. In the setting of a WD, endothelial ERalpha signaling contributes to vascular stiffening in females. The precise mechanisms underlying the detrimental effects of endothelial ERalpha in the setting of a WD remain to be elucidated. PMID- 26872092 TI - Gallium(III) Tetraphenylporphyrinates Containing Hydrosulfide and Thiolate Ligands: Structural Models for Sulfur-Bound Iron(III) Hemes. AB - Gallium(III) tetraphenylporphyrinates (TPP) containing anionic sulfur ligands have been prepared and characterized in the solid state and solution. The complexes serve as structural models for iron(III) heme sites containing sulfur coordination that otherwise prove challenging to synthesize due to the propensity for reduction to iron(II). The compounds prepared include the first well characterized example of a trivalent metalloporphyrinate containing a terminal hydrosulfide ligand, [Ga(SH)(TPP)], as well as [Ga(SEt)(TPP)], [Ga(SPh)(TPP)], and [Ga(SSi(i)Pr3)(TPP)]. The stability of these compounds toward reduction has permitted an investigation of their solid-state structures and electrochemistry. The structural features and reaction chemistry of the complexes in relation to their iron(III) analogs is discussed. PMID- 26872091 TI - Transient Suppression of TGFbeta Receptor Signaling Facilitates Human Islet Transplantation. AB - Although islet transplantation is an effective treatment for severe diabetes, its broad application is greatly limited due to a shortage of donor islets. Suppression of TGFbeta receptor signaling in beta-cells has been shown to increase beta-cell proliferation in mice, but has not been rigorously examined in humans. Here, treatment of human islets with a TGFbeta receptor I inhibitor, SB 431542 (SB), significantly improved C-peptide secretion by beta-cells, and significantly increased beta-cell number by increasing beta-cell proliferation. In addition, SB increased cell-cycle activators and decreased cell-cycle suppressors in human beta-cells. Transplantation of SB-treated human islets into diabetic immune-deficient mice resulted in significant improvement in blood glucose control, significantly higher serum and graft insulin content, and significantly greater increases in beta-cell proliferation in the graft, compared with controls. Thus, our data suggest that transient suppression of TGFbeta receptor signaling may improve the outcome of human islet transplantation, seemingly through increasing beta-cell number and function. PMID- 26872096 TI - Time and order of eruption of first functional teeth in the upper jaw of post larval life of Sicyopterus japonicus (Gobiidiae: Sicydiinae) during cranial metamorphosis at the time of river recruitment. AB - OBJECTIVE: The present study was aimed at elucidating the time and order of eruption of first functional teeth in the upper jaw of post-larval life of Sicyopterus japonicus (S. japonicus) during cranial metamorphosis at the time of river recruitment. DESIGN: Fishes were caught at the post-larval stage at a river mouth and maintained for 7 days in a water tank. Each of 10 specimens was evaluated every day for 7 days by using microcomputed tomography, scanning electron microscopy, and light microscopy with peculiar attention to the development of the upper jaw teeth. RESULTS: Fishes caught at the river mouth were mostly transparent, with a rostral terminal mouth, and no teeth could be found in either the upper or lower jaw. At 2 days after collection, the mouth position changed from terminal to subterminal, resulting from a change in head shape. The initial eruption of first functional teeth was detected at the anterior two-thirds region of each upper jaw. These teeth erupted in adjacent positions, most had a tricuspid crown, and they represented miniature versions of adult teeth. At 5 days, the position of the mouth became further relocated from terminal rostral to ventral. The number of erupted teeth increased, followed by spreading of them anteriorly and posteriorly. At 7 days, they formed a single row of close-set tricuspid teeth along the entire length of each upper jaw. CONCLUSIONS: The present study demonstrated that even under laboratory conditions a rapid and drastic cranial metamorphosis took place within a week after the time of collection of post-larval S. japonicus from a river. The eruption of first functional teeth in the upper jaw of S. japonicus, which teeth are adapted to scraping algae off the substrate, was initially detected at 2 days after collection, and first functional dentition of the upper jaw was set up within 7 days after it. PMID- 26872095 TI - Human neutrophil peptide-1 affects matrix metalloproteinase-2, -8 and -9 secretions of oral squamous cell carcinoma cell lines in vitro. AB - OBJECTIVES: The present study aimed to investigate the effect of HNP-1 on the matrix metalloproteinase (MMP)-2, -8 and -9 secretions of two oral squamous cell carcinoma (OSCC) cell lines (UT-SCC-43A and UT-SCC-43B). DESIGN: In all experiments, the two OSCC cell lines were incubated with graded concentrations (0, 1, 5, and 10 MUg/ml) of HNP-1 for 24 and 48 h. Cell viability was measured using a colorimetric proliferation test and cell death was analyzed with a colorimetric cytotoxicity detection kit. Enzyme activity of MMP-2 and MMP-9 was detected by using gelatin zymography, and molecular weight forms of MMP-8 were determined by Western-blot and a densitometric quantitation method. RESULTS: Both cell lines showed a significant increase in LDH toxicity at 24h (UT-SCC-43A: p=0.005 & UT-SCC-43B: p=0.014). Reduced gelatinolytic activities of proMMP-2 were detected in UT-SCC-43B cell line after 24 and 48 h of incubation with HNP-1 (1 MUg/ml: p<0.001, 5 MUg/ml: p<0.001, and 10 MUg/ml: p=0.0225). MMP-8 levels of both cell lines decreased at 200-250 kDa after 24h of incubation, while after 48 h only UT-SCC-43B decreased at 45-50 kDa. CONCLUSIONS: Our results indicate that HNP-1 suppresses the secretion of MMP-2, -8, and -9 in OSCC cell lines. PMID- 26872098 TI - Normobaric oxygen therapy inhibits HIF-1alpha and VEGF expression in perihematoma and reduces neurological function defects. AB - It is unknown whether normobaric oxygen (NBO) therapy exerts neuroprotective effects against human intracerebral hemorrhage (ICH). In this study, the potential of NBO therapy for salvaging brain damage following ICH was investigated in a rodent model with oxygen delivered at different concentrations. A total of 164 male Sprague-Dawley rats were induced with ICH using a collagenase injection and divided randomly into one ICH control group (no treatment, n=86) and three NBO treatment groups (35, 50, or 90% oxygen, n=26/group). Twenty-six rats were used as sham controls. The Neurological Severity Score (NSS) was evaluated. Contents of brain water, hypoxia-inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) were measured in the perihematoma. A cellular apoptosis assay was performed. Compared with the sham control group, the ICH control group had higher NSS following ICH, which peaked at 24 h and began to decrease after 72 h. ICH rats also showed higher contents of brain water, HIF-1alpha, and VEGF (peaked at 72 h) in the ipsilateral perihematoma tissue than in the contralateral brain tissue. Compared with the ICH control group, all NBO groups showed improved NSSs, decreased contents of brain water, HIF-1alpha and VEGF, and fewer apoptotic cells in the perihematoma at 72 h after ICH, but statistical significance of these changes was achieved only with oxygen delivered at 90% (P<0.05, two-way analysis of variance). These results suggest that NBO therapy with oxygen delivered at 90% conferred best neuroprotection to ICH rats, potentially through amelioration of brain edema by suppressing HIF 1alpha and VEGF expression in the perihematoma. PMID- 26872097 TI - Guidewire Catheter Exchange in Pediatric Oncology: Indications, Postoperative Complications, and Outcomes. AB - BACKGROUND: Maintaining long-term central venous catheters (CVCs) in children undergoing chemotherapy can be challenging. Guidewire catheter exchange (GCE) replaces a CVC without repeat venipuncture. This study evaluated the indications, success rate, and complications of GCE in a large cohort of pediatric cancer patients. PROCEDURE: Medical records of pediatric cancer patients who underwent GCE at our institution between 2003 and 2013 were retrospectively reviewed. Variables analyzed included gender, age at GCE, primary cancer diagnosis, indication for GCE, absolute neutrophil count (ANC) at GCE, vein used, success rate, and postoperative complications (<30 days after exchange). RESULTS: A total of 435 GCEs performed in 407 patients (230 males and 177 females) were reviewed. Median age at GCE was 8 years (range, 0.2-24). Acute lymphoblastic leukemia was the most common diagnosis (50.6%). The primary indication for GCE was the desire to have an alternative type of CVC (71%). Other indications included catheter displacement (17%), catheter malfunction (11%), and catheter infection (1%). Median ANC at GCE was 2,581/mm(3) (range, 0-43,400). Left subclavian vein was more commonly used (57.7%). The success rate of GCE was 93.4% (406 of 435 procedures, 95% confidence interval: 91.0-97.5%). A total of 33 (7.5%) postoperative complications occurred including central line associated bloodstream infection (CLABSI) (n = 20, 4.5%), catheter dislodgement (n = 6, 1.4%), and catheter malfunction (n = 7, 1.6%). CONCLUSIONS: We conclude that GCE in pediatric cancer patients is associated with a high success rate and a low risk of complications. The most common postoperative complication, CLABSI, occurred at a rate significantly lower than following de novo CVC placement. PMID- 26872099 TI - Topographic analysis of the skull vibration-induced nystagmus test with piezoelectric accelerometers and force sensors. AB - Vibration-induced nystagmus is elicited by skull or posterior cervical muscle stimulations in patients with vestibular diseases. Skull vibrations delivered by the skull vibration-induced nystagmus test are known to stimulate the inner ear structures directly. This study aimed to measure the vibration transfer at different cranium locations and posterior cervical regions to contribute toward stimulus topographic optimization (experiment 1) and to determine the force applied on the skull with a hand-held vibrator to study the test reproducibility and provide recommendations for good clinical practices (experiment 2). In experiment 1, a 100 Hz hand-held vibrator was applied on the skull (vertex, mastoids) and posterior cervical muscles in 11 healthy participants. Vibration transfer was measured by piezoelectric sensors. In experiment 2, the vibrator was applied 30 times by two experimenters with dominant and nondominant hands on a mannequin equipped to measure the force. Experiment 1 showed that after unilateral mastoid vibratory stimulation, the signal transfer was higher when recorded on the contralateral mastoid than on the vertex or posterior cervical muscles (P<0.001). No difference was observed between the different vibratory locations when vibration transfer was measured on vertex and posterior cervical muscles. Experiment 2 showed that the force applied to the mannequin varied according to the experimenters and the handedness, higher forces being observed with the most experienced experimenter and with the dominant hand (10.3 +/- 1.0 and 7.8 +/- 2.9 N, respectively). The variation ranged from 9.8 to 29.4% within the same experimenter. Bone transcranial vibration transfer is more efficient from one mastoid to the other mastoid than other anatomical sites. The mastoid is therefore the optimal site for skull vibration-induced nystagmus test in patients with unilateral vestibular lesions and enables a stronger stimulation of the healthy side. In clinical practice, the vibrator should be placed on the mastoid and should be held by the clinician's dominant hand. PMID- 26872100 TI - Electrophysiological evidence that top-down knowledge controls working memory processing for subsequent visual search. AB - Items in working memory guide visual attention toward a memory-matching object. Recent studies have shown that when searching for an object this attentional guidance can be modulated by knowing the probability that the target will match an item in working memory. Here, we recorded the P3 and contralateral delay activity to investigate how top-down knowledge controls the processing of working memory items. Participants performed memory task (recognition only) and memory-or search task (recognition or visual search) in which they were asked to maintain two colored oriented bars in working memory. For visual search, we manipulated the probability that target had the same color as memorized items (0, 50, or 100%). Participants knew the probabilities before the task. Target detection in 100% match condition was faster than that in 50% match condition, indicating that participants used their knowledge of the probabilities. We found that the P3 amplitude in 100% condition was larger than in other conditions and that contralateral delay activity amplitude did not vary across conditions. These results suggest that more attention was allocated to the memory items when observers knew in advance that their color would likely match a target. This led to better search performance despite using qualitatively equal working memory representations. PMID- 26872101 TI - Improved Photoresponse Performance of Self-Powered ZnO/Spiro-MeOTAD Heterojunction Ultraviolet Photodetector by Piezo-Phototronic Effect. AB - Strain-induced piezoelectric potential (piezopotential) within wurtzite structured ZnO can engineer the energy-band structure at a contact or a junction and, thus, enhance the performance of corresponding optoelectronic devices by effectively tuning the charge carriers' separation and transport. Here, we report the fabrication of a flexible self-powered ZnO/Spiro-MeOTAD hybrid heterojunction ultraviolet photodetector (UV PD). The obtained device has a fast and stable response to the UV light illumination at zero bias. Together with responsivity and detectivity, the photocurrent can be increased about 1-fold upon applying a 0.753% tensile strain. The enhanced performance can be attributed to more efficient separation and transport of photogenerated electron-hole pairs, which is favored by the positive piezopotential modulated energy-band structure at the ZnO-Spiro-MeOTAD interface. This study demonstrates a promising approach to optimize the performance of a photodetector made of piezoelectric semiconductor materials through straining. PMID- 26872104 TI - Electrochemical functionalization of Au by aminobenzene and 2-aminotoluene. AB - Au surfaces are functionalized by aminobenzene (AB) and 2-aminotoluene (AT) using the electrochemical reduction of diazotized 1,4-diaminobenzene and 2,5 diaminotoluene. The IR spectroscopic measurements reveal the successful modification of Au surfaces by AB and AT. Both types of layers show similar thicknesses as obtained by microgravimetric measurements via electrochemical quartz crystal microbalance (EQCM). However, the faradaic efficiency for the grafting of AT onto an EQCM-Au sensor was 6% compared to 41% for the grafting of AB. This behavior points to a steric hindrance during the binding of AT to the EQCM surface induced by the additional methyl group present in the toluene derivative. The AB and AT functionalized surfaces have been further modified by the amidation reaction of EDC/NHS activated 4-nitrobenzoic acid. This model system reveals that the amidation reaction is slightly hindered in case of the AT layer due to the presence of the methyl group close to the amino group. This behavior leads to a four times less amount of amide bonds at the AT compared to AB modified Au surfaces as obtained from IR spectroscopic measurements. PMID- 26872103 TI - Curcumin Ameliorates Reserpine-Induced Gastrointestinal Mucosal Lesions Through Inhibiting IkappaB-alpha/NF-kappaB Pathway and Regulating Expression of Vasoactive Intestinal Peptide and Gastrin in Rats. AB - The objective of our study was to investigate whether curcumin protects against reserpine-induced gastrointestinal mucosal lesions (GMLs) in rats and to explore the mechanism of curcumin's action. Sprague-Dawley rats were randomly divided into four groups: control group, reserpine-treated group, reserpine treatment group with curcumin at high dose (200 mg/kg), and reserpine treatment group with curcumin at low dose (100 mg/kg). Rats in reserpine-treated group were induced by intraperitoneally administered reserpine (0.5 mg/kg) for 28 days. TUNEL staining and hematoxylin and eosin staining were used to evaluate the apoptotic cells and morphologic changes. In addition, to explore the mechanism of curcumin in protecting GMLs, we used serum of experimental rats to assess the level of vasoactive intestinal peptide (VIP), gastrin, interleukin-6, interleukin-10, tumor necrosis factor-alpha and interferon-gamma by ELISA and radioimmunoassay. The protein levels of NF-kappaB, p-IkappaB-alpha, IkappaB-alpha, Bcl-2, Bax, and cleaved-caspase-3 were examined by western blot analysis. Data were analyzed with SPSS 19.0 software package. Curcumin treatment prevented tissue damage and cell death in the reserpine-treated rats and effectively decreased inflammatory response and balanced the expression of VIP and gastrin in the reserpine-treated rats. NF-kappaB, p-IkappaB-alpha, Bax, and cleaved-caspase-3 were increased in the reserpine group, but the curcumin high-dose group inhibited them. Curcumin can target the IkappaB-alpha/NF-kappaB pathway to inhibit inflammatory response and regulate the level of VIP and gastrin in reserpine-induced GML rats. PMID- 26872102 TI - Time Course and Predictors of Structural Disease Progression in Pulmonary Metastases Arising from Follicular Cell-Derived Thyroid Cancer. AB - BACKGROUND: With the advent of molecular targeted therapy for the management of radioactive iodine (RAI) refractory, progressive metastatic thyroid cancer, it becomes important to define the time course and risk factors for structural disease progression in follicular cell-derived thyroid cancer (FCDTC) patients. This will help in defining the optimal time to start these therapies and better define their impact on structural disease progression. OBJECTIVES: This retrospective review of 199 consecutive patients with FCDTC presenting with lung metastasis examined the progression-free survival (PFS) in thyroid cancer patients with lung metastasis treated with surgery and RAI, and who had not received molecular targeted therapy or chemotherapy. RESULTS: The median overall survival (OS) was 10.45 years, while the median PFS was 3.65 years. A strong correlation was found between OS and PFS. PFS is shorter in patients with RAI refractory disease, poorly differentiated/Hurthle cell histologies, male sex, fluorodeoxyglucose-avid metastatic foci, older age (>45 years), and pulmonary metastases >1 cm. At final follow-up (a median of 6.9 years from lung metastasis diagnosis), 68% of the patients had progressed and 46% had died. CONCLUSIONS: With the exception of younger patients with low disease burden, most patients presenting with lung metastasis from FCDTC (RAI avid and RAI refractory) using standard-of-care approaches will have disease progression on long-term follow-up. Additional studies are needed to identify novel therapies that would improve the PFS of such patients. PMID- 26872105 TI - Optimizing diabetes control in people with Type 2 diabetes through nurse-led telecoaching. AB - AIMS: To study the effect of a target-driven telecoaching intervention on HbA1c and other modifiable risk factors in people with Type 2 diabetes. METHODS: We conducted a randomized controlled trial in patients receiving hypoglycaemic agents. The primary outcome was HbA1c level at 6 months in the entire sample and in a subgroup with HbA1c levels >= 53 mmol/mol (7%) at baseline. Secondary outcomes were HbA1c at 18 months; total cholesterol, LDL, HDL, triglycerides, blood pressure, BMI and proportion of people who had achieved guideline recommended targets at 6 and 18 months. RESULTS: A total of 287 participants were randomized to telecoaching and 287 to usual care. The mean (sd) baseline HbA1c level was 53 (11) mmol/mol [7.0 (1.0)%] overall and 63 (10) mmol/mol [7.9 (0.9)%] in the elevated HbA1c subgroup. At 6 months, the between-group differences in favour of telecoaching were: HbA1c -2 (95% CI -4; -1) mmol/mol [-0.2 (95% CI 0.3;-0.1)%; P=0.003] overall and -4 (95% CI -7; -2) mmol/mol [-0.4 (95% CI -0.7; 0.2)%; P=0.001] in the elevated HbA1c subgroup; BMI -0.4 kg/m(2) (95% CI -0.6; 0.1; P=0.003); total cholesterol -6 mg/dl (95% CI -11; -1, P=0.012). The proportion of participants on target for the composite of HbA1c , LDL and blood pressure increased by 8.9% in the intervention group and decreased by 1.3% in the control group (P=0.011). At 18 months, the difference in HbA1c was: -2 (95% CI 3;-0) mmol/mol [-0.2 (95% CI -0.3; -0.0)%; P=0.046] overall and -4 (-7; -1) mmol/mol [-0.4 (95% CI -0.7; -0.1)%; P=0.023] in the elevated HbA1c subgroup. CONCLUSION: Nurse-led telecoaching improved glycaemic control, total cholesterol levels and BMI in people with Type 2 diabetes. Twelve months after the intervention completion, there were sustained improvements in glycaemic control. PMID- 26872106 TI - Change in plasma a disintegrin and metalloprotease with thrombospondin type-1 repeats-13 and von Willebrand factor levels in venous thromboembolic patients. AB - OBJECTIVES: Venous thromboembolism (VTE) is an important cause of morbidity and mortality. A disintegrin and metalloprotease with thrombospondin type-1 repeats 13 (ADAMTS-13) is a metalloprotease that cleaves plasma von Willebrand factor (VWF) multimers. The presence of large VWF multimers in the plasma due to ADAMTS 13 deficiency is the main factor in the pathogenesis of thrombotic thrombocytopenic purpura. The present study aimed to investigate the relation of plasma levels of ADAMTS-13 and VWF antigen with VTE. METHODS: The present study included 30 patients with VTE and age- and gender-matched 30 healthy subjects. Patients with any condition (diabetes, icterus, hyperlipidemia, physical, or surgical trauma, acute coronary syndrome, pregnancy, renal insufficiency, liver disease, malignancy, collagen tissue disease, chronic or acute inflammation, drug use affecting thrombocyte function) that could affect plasma VWF antigen or ADAMTS-13 levels were excluded. Plasma ADAMTS-13 and VWF antigen levels in the VTE and control groups were quantitatively determined by enzyme-linked immunosorbent assay method. RESULTS: The median ADAMTS-13 level was 280 ng/ml (minimum-maximum, 70-1120 ng/ml) in the VTE group and 665 ng/ml (minimum-maximum, 350-2500 ng/ml) in the control group; the difference between the groups was significant (P < 0.0001). The mean VWF antigen level was 1750 +/- 616 mU/ml in the patient group, which was significantly higher than that of the control group (950 +/- 496 mU/ml) (P < 0.0001). CONCLUSION: Significantly lower ADAMTS-13 levels and significantly higher VWF antigen levels were concluded to be the result of a pathological process rather than an etiological factor for VTE. PMID- 26872107 TI - Improving the Impact and Implementation of Disaster Education: Programs for Children Through Theory-Based Evaluation. AB - A main weakness in the evaluation of disaster education programs for children is evaluators' propensity to judge program effectiveness based on changes in children's knowledge. Few studies have articulated an explicit program theory of how children's education would achieve desired outcomes and impacts related to disaster risk reduction in households and communities. This article describes the advantages of constructing program theory models for the purpose of evaluating disaster education programs for children. Following a review of some potential frameworks for program theory development, including the logic model, the program theory matrix, and the stage step model, the article provides working examples of these frameworks. The first example is the development of a program theory matrix used in an evaluation of ShakeOut, an earthquake drill practiced in two Washington State school districts. The model illustrates a theory of action; specifically, the effectiveness of school earthquake drills in preventing injuries and deaths during disasters. The second example is the development of a stage step model used for a process evaluation of What's the Plan Stan?, a voluntary teaching resource distributed to all New Zealand primary schools for curricular integration of disaster education. The model illustrates a theory of use; specifically, expanding the reach of disaster education for children through increased promotion of the resource. The process of developing the program theory models for the purpose of evaluation planning is discussed, as well as the advantages and shortcomings of the theory-based approaches. PMID- 26872109 TI - Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients. AB - BACKGROUND: Ezetimibe has been reported to inhibit viral entry and to reduce BMI and has been proposed as a novel therapeutic agent for chronic hepatitis C (CHC), potentiating the effects of pegylated interferon and ribavirin (peg-IFN/RBV). OBJECTIVE: The aim of the study was to assess the effects of ezetimibe coadministration with peg-IFN/RBV combination on the early virological response (EVR) rates in nonobese and obese patients with CHC genotype 4 (CHC-4). PATIENTS AND METHODS: A total of 144 CHC-4 patients were divided into two groups; group 1 included nonobese patients (n=76) and group 2 included obese patients (n=68). Each group was further subclassified into equal control and treated groups. The control groups received peg-IFN/RBV combination for 24 weeks, and the treated groups received peg-IFN/RBV plus ezetimibe for 12 weeks and then only peg-IFN/RBV for the remaining 12 weeks. RESULTS: The study revealed that EVR significantly improved in the obese patients (85.3 vs. 64.7% in the treated and control groups, respectively, at P<0.05) without any significant improvement in the nonobese patients. Biochemical responses (defined as normalization of alanine aminotransferase at week 12) were markedly improved in the treated groups in both the nonobese and obese groups compared with their respective controls. CONCLUSION: The addition of ezetimibe to peg-IFN/RBV combination significantly improves EVR rates in obese patients compared with nonobese patients, and remarkably improves the biochemical responses in both obese and nonobese patients with CHC-4. This may shed light on a new strategy for the treatment of CHC, particularly in obese Egyptian patients. PMID- 26872108 TI - Destruction of the World Trade Center Towers. Lessons Learned from an Environmental Health Disaster. AB - The assault and subsequent collapse of the World Trade Center towers in New York City on September 11, 2001 (9/11), released more than a million tons of debris and dust into the surrounding area, engulfing rescue workers as they rushed to aid those who worked in the towers, and the thousands of nearby civilians and children who were forced to flee. In December 2015, almost 15 years after the attack, and 5 years after first enactment, Congress reauthorized the James Zadroga 9/11 Health and Compensation Act, a law designed to respond to the adverse health effects of the disaster. This reauthorization affords an opportunity to review human inhalation exposure science in relation to the World Trade Center collapse. In this Special Article, we compile observations regarding the collective medical response to the environmental health disaster with a focus on efforts to address the adverse health effects experienced by nearby community members including local residents and workers. We also analyze approaches to understanding the potential for health risk, characterization of hazardous materials, identification of populations at risk, and shortfalls in the medical response on behalf of the local community. Our overarching goal is to communicate lessons learned from the World Trade Center experience that may be applicable to communities affected by future environmental health disasters. The World Trade Center story demonstrates that communities lacking advocacy and preexisting health infrastructures are uniquely vulnerable to health disasters. Medical and public health personnel need to compensate for these vulnerabilities to mitigate long-term illness and suffering. PMID- 26872111 TI - Idiopathic non-cirrhotic portal hypertension: the tip of the obliterative portal venopathies iceberg? PMID- 26872110 TI - Primary sclerosing cholangitis associated with inflammatory bowel disease: an observational study in a Southern Europe population focusing on new therapeutic options. AB - BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with a strong association with inflammatory bowel disease (IBD). Medical treatment for PSC is still disappointing, whereas immunomodulators and biologics have been proven to be effective in IBD. AIMS: This study aimed to analyze (i) the natural history of patients with PSC with or without IBD and (ii) the long term efficacy of biologics in patients with PSC and concomitant IBD or rheumatological disorders. PATIENTS AND METHODS: This study included 92 consecutive PSC patients, 50 (54.3%) men and 42 (45.7%) women, with a mean age of 32.0+/-14.3 years at diagnosis and a mean follow-up duration of 103.8+/-86 months. Forty-nine (53.3%) patients had associated IBD (38 ulcerative colitis, 10 Crohn's disease, one indeterminate colitis). RESULTS: No significant differences were found between PSC patients with and without associated IBD in terms of liver transplantation, cancer, and death rates. Cholangiocarcinoma was only identified among patients with PSC alone, whereas other cancers (hepatocellular carcinoma, colorectal, and gallbladder cancer) were found only in the group with associated IBD. Five PSC patients were treated with biologic agents: three with adalimumab and one with infliximab for IBD or for rheumatoid arthritis, and one patient with rituximab for rheumatoid arthritis. Adalimumab decreased alkaline phosphatase in two of three patients after 6 and 12 months, infliximab reduced gamma glutamyltransferase after 6 and 12 months, but liver function tests tended to deteriorate thereafter. Cholangiography changes remained stable in all patients. CONCLUSION: Biologic agents may improve liver function tests in PSC patients, but may be associated with adverse events including deterioration of liver function. PMID- 26872112 TI - A Naturalistic Randomized Placebo-Controlled Trial of Extended-Release Metformin to Prevent Weight Gain Associated With Olanzapine in a US Community-Dwelling Population. AB - OBJECTIVE: This 24-week pilot study assessed the efficacy, tolerability, and safety of adjunctive metformin versus placebo for the prevention of olanzapine associated weight gain in community-dwelling adult patients with schizophrenia, schizoaffective disorder, bipolar disorder, or major depression with psychotic features. METHODS: In a double-blind study, 25 patients were randomly assigned to receive 24 weeks of either olanzapine plus metformin or olanzapine plus placebo. Metformin extended release was titrated to 2000 mg daily as tolerated. No other antipsychotics were allowed, whereas psychotropic medications including antidepressants and mood stabilizers were permitted. The primary outcome measures were change in body weight and homeostatic model assessment for insulin resistance from baseline to week 24. RESULTS: The intent-to-treat population comprised patients who had 1 or more post-baseline visit. Mean change in body weight for the olanzapine plus metformin (O/M) group was 5.5 lb, which was less than the 12.8 lb gain for the olanzapine plus placebo (O/P) group (P < 0.05). Compared with O/P group who gained 7% of their body weight, patients in the O/M group gained 3% (P < 0.037). Body mass index change in the O/M group was 0.85 versus 2.02 in the O/P group (P < 0.045). There was a trend for a greater increase in baseline to end point homeostatic model assessment for insulin resistance and waist circumference in the O/P group versus the O/M group. CONCLUSIONS: In this naturalistic sample of typical US community-dwelling patients, metformin was effective and well tolerated for the prevention of olanzapine-associated weight gain. Adjunctive metformin should be studied in a similar but larger population to determine its role in the prevention of olanzapine-associated weight gain. PMID- 26872113 TI - Impact of Pharmacogenetic Markers of CYP2D6 and DRD2 on Prolactin Response in Risperidone-Treated Thai Children and Adolescents With Autism Spectrum Disorders. AB - OBJECTIVE: The aim of the study was to identify the impact of pharmacogenetic markers associated with prolactin concentration in risperidone-treated children and adolescents with autism spectrum disorders. METHODS: One hundred forty-seven children and adolescents with autism, aged 3 to 19 years, received risperidone. The clinical data of patients were recorded from medical records. Prolactin levels were measured by chemiluminescence immunoassay. Three CYP2D6 single nucleotide polymorphisms, CYP2D6*4 (1846G>A), *10 (100C>T), and *41 (2988G>A), 1 gene deletion (*5), and DRD2 Taq1A (rs1800497) polymorphism were genotyped by TaqMan real-time polymerase chain reaction. RESULTS: The 3 common allelic frequencies were CYP2D6*10 (55.10%), *1 (32.65%), and *5 (6.12%), respectively. Patients were grouped according to their CYP2D6 genotypes. There was no significant correlation between the concentrations of prolactin among the CYP2D6 genotypes. In addition, there were no statistical differences in the prolactin response among the CYP2D6-predicted phenotypes of extensive metabolizer and intermediate metabolizer. The DRD2 genotype frequencies were Taq1A A2A2 (38.77%), A1A2 (41.50%), and A1A1 (19.73%), respectively. There were statistically significant differences in prolactin level of patients among the 3 groups (P = 0.033). The median prolactin level in patients with DRD2 Taq1A A2A2 (17.80 ng/mL) was significantly higher than A1A2 (17.10 ng/mL) and A1A1 (12.70 ng/mL). CONCLUSIONS: DRD2 Taq1A A2A2 polymorphisms may play a significant role in the hyperprolactinemia- associated with risperidone treatment in children and adolescent with autism spectrum disorder. Many drugs used chronically in psychiatric diseases exert their effects mainly through the dopamine D2 receptor. It is therefore possible that these drugs could alter the expression of any dopamine receptor, thus affecting the pharmacodynamics characteristics and toxicity of drug substrates during pharmacotherapy. PMID- 26872114 TI - Risk of New-Onset Diabetes After Long-Term Treatment With Clozapine in Comparison to Other Antipsychotics in Patients With Schizophrenia. AB - It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking. PMID- 26872115 TI - Predicting Weight Gain in Patients Treated With Clozapine: The Role of Sex, Body Mass Index, and Smoking. AB - OBJECTIVES: Weight gain on clozapine is highly variable and poorly predictable. Its mechanisms are not well understood. This study explores the factors that predict weight gain between 3 and 12 months of clozapine therapy in community dwelling patients. METHODS: We conducted a retrospective audit of patients attending an outpatient clozapine clinic. Weight change from 3 to 12 months of therapy was recorded, expressed as a percentage of the 3-month weight. Univariate analyses compared percent weight change according to sex, smoking status, country of birth, and baseline body mass index. Correlations between weight gain, age, and clozapine dose were explored. A general linear model identified independent predictors of weight gain. RESULTS: The mean weight change from 3 to 12 months in 117 patients was +3.1% (range, -17% to +30%). Females gained more weight than males (+5.5% vs +1.3%, P = 0.01), smokers gained more than nonsmokers (+5.1% vs +1.2%, P = 0.02), and obese patients gained less than normal or overweight individuals (0.15% vs 4.6% and 5.2%, respectively, P = 0.01). Age and clozapine dose had no relation to weight change. On multivariate analysis, baseline BMI and smoking status remained independent predictors of percent weight change in females. These 2 predictors explained 25% of weight change in females in the first 3 to 12 months of therapy. These associations were not observed in males. CONCLUSIONS: We hypothesize that smoking affects weight change by promoting clozapine metabolism to norclozapine via cytochrome P450 enzymes. Verifying this hypothesis and exploring the mechanisms underpinning the sex dichotomy are areas for further research. PMID- 26872116 TI - Eosinophilia Associated With Olanzapine. PMID- 26872118 TI - The Delirium Related to Oral Paliperidone in Dementia: A Case Report. PMID- 26872119 TI - A Case Report of Camptocormia Coinciding With Olanzapine Use. PMID- 26872117 TI - Systematic Review of Pharmacological and Behavioral Treatments for Skin Picking Disorder. AB - Skin picking disorder (SPD) is a newly recognized psychiatric disorder in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. A systematic review was conducted to assess the efficacy of pharmacological and behavioral interventions for SPD. Electronic databases were searched for randomized controlled trials (RCTs) or uncontrolled trials involving at least 10 subjects that examined the efficacy of pharmacological and behavioral interventions for SPD. We examined the improvement associated with interventions compared with inactive control conditions in RCTs and improvement over time in uncontrolled trials and within the treatment arms of RCTs. We stratified studies on the basis of intervention type. Meta-analysis included 11 studies. All interventions (including inactive control conditions) demonstrated significant improvement over the course of short-term clinical trials in SPD. Only behavioral treatments demonstrated significant benefits compared with inactive control conditions. There was no evidence from RCTs that pharmacotherapy with selective serotonin reuptake inhibitors or lamotrigine were more effective at treating SPD than placebo. Our meta-analysis suggests that subjects with SPD show significant improvement during short-term trials, regardless of the efficacy of the underlying intervention. This finding suggests that uncontrolled trials are of particularly limited utility for assessing efficacy of treatments in SPD. Future research should concentrate on developing larger placebo-controlled RCTs to examine efficacy of novel pharmacological agents. In addition, research should focus on improving accessibility of behavioral treatments with demonstrated efficacy for SPD. PMID- 26872120 TI - Clozapine Underutilization in the Treatment of Schizophrenia: How Can Clozapine Prescription Rates Be Improved? PMID- 26872121 TI - Reply to Comments From Dr Lozano, et al--Concerning the Prevalence of Lithium Associated Hyperparathyroidism. PMID- 26872122 TI - Electrochemical Deposition of Azobenzene-Containing Network Films with High Contrast and Stable Photoresponse. AB - To fabricate stable photoresponsive films and devices, a cross-linked network that firmly fixes the position of the chromophores is an ideal structure, because aggregation and/or phase separation effects of chromophores in matrix can be effectively restrained in such robust films. Herein, the in situ electrochemical deposition (ED) of azo-based precursors containing multielectroactive carbazole units is utilized to construct highly cross-linked photoresponsive films. 2-(4 (9,9-bis(6-(9H-carbazol-9-yl)hexyl)-9H-fluoren-2-yl)phenyl)-1-(4-(9,9-bis(6-(9H carbazol-9-yl)hexyl)-9H-fluoren-7-yl)phenyl)diazene (BFCzAzo) with high solvability in electrolyte solution, high electroactivity, and highly efficient photoresponsive ability is synthesized by Suzuki coupling reaction as a kind of ED precursor. A highly cross-linked photoresponsive film is fabricated by ED method using BFCzAzo as ED precursor. The film can be patterned in large area by irradiation with interfering laser beam (355 nm), and the pattern possesses excellent thermal stability and insoluble ability in both organic and inorganic solvents. Excellent reversibility of the nanostructures is demonstrated by irradiation with 550 nm laser beam. PMID- 26872123 TI - A pilot trial of brief group cognitive-behavioral treatment for insomnia in an adult cancer survivorship program. AB - BACKGROUND: Cognitive-behavioral therapy for insomnia (CBT-Insomnia) is effective, yet rarely available for cancer survivors. This is unfortunate because survivors are at elevated risk for insomnia, which is associated with significant health consequences in this already at-risk population. Barriers to delivering CBT-Insomnia in oncology settings include a lack of trained providers, distance to cancer centers, and treatment duration. PURPOSE: To address insomnia treatment barriers, we adapted standard CBT-Insomnia treatment and evaluated a pilot group based approach for feasibility and efficacy in an adult cancer survivorship program. METHODS: Thirty-eight cancer survivors (mean age = 52.2 years) enrolled in our three-session program delivered over 1 month. They were primarily diagnosed with breast cancer (58.6%) and were an average of 6.0 years post diagnosis and 3.6 years post-treatment. Participants completed sleep logs throughout the study and measures of sleep at baseline and week 4. RESULTS: Participants reported experiencing insomnia symptoms an average of 2.4 years, with 89.7% indicating that the cancer experience had caused/exacerbated symptoms. Significant pre/post-intervention group improvements in sleep efficiency (77.3% to 88.5%), sleep quality, and insomnia symptoms were reported (all ps < .01). Less than 1 in 3 had discussed insomnia symptoms with their oncology providers in the prior year. CONCLUSIONS: Pilot data indicate that a brief, group-based CBT Insomnia intervention in a survivorship setting is both feasible and efficacious. There is a need to increase awareness about insomnia and its treatment among both cancer survivors and oncology providers. If validated in future studies, this novel approach can improve cancer survivors' access to much needed insomnia treatment. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26872124 TI - Fully unsupervised inter-individual IR spectral histology of paraffinized tissue sections of normal colon. AB - In label-free Fourier-transform infrared histology, spectral images are individually recorded from tissue sections, pre-processed and clustered. Each single resulting color-coded image is annotated by a pathologist to obtain the best possible match with tissue structures revealed after Hematoxylin-Eosin staining. However, the main limitations of this approach are the empirical choice of the number of clusters in unsupervised classification, and the marked color heterogeneity between the clustered spectral images. Here, using normal murine and human colon tissues, we developed an automatic multi-image spectral histology to simultaneously analyze a set of spectral images (8 images mice samples and 72 images human ones). This procedure consisted of a joint Extended Multiplicative Signal Correction (EMSC) to numerically deparaffinize the tissue sections, followed by an automated joint K-Means (KM) clustering using the hierarchical double application of Pakhira-Bandyopadhyay-Maulik (PBM) validity index. Using this procedure, the main murine and human colon histological structures were correctly identified at both the intra- and the inter-individual levels, especially the crypts, secreted mucus, lamina propria and submucosa. Here, we show that batched multi-image spectral histology procedure is insensitive to the reference spectrum but highly sensitive to the paraffin model of joint EMSC. In conclusion, combining joint EMSC and joint KM clustering by double PBM application allows to achieve objective and automated batched multi-image spectral histology. PMID- 26872125 TI - Studies of the structure and phase transitions of nano-confined pentanedithiol and its application in directing hierarchical molecular assemblies on Au(1 1 1). AB - Directing molecular devices into pre-designed integrated electronic circuits while enforcing selectivity and hierarchy is an inherent challenge for molecular electronics. Here we explore ways to direct the assembly of electrically-active molecular monolayers into specific locations as well as controlling their internal organization. We have accomplished this by two consecutive surface reactions: (1) forming pentanedithiol (C5DT) domains within an inert alkanethiol self-assembled monolayer (SAM) on Au; and (2) selectively binding porphyrin derivatives to the C5DT domains. The C5DT domains were fabricated by phase segregation during co-adsorption from a mixed C5DT/dodecanethiol (C12) solution and nanografting with Atomic Force Microscopy (AFM). AFM revealed that co absorbed and nanografted C5DT domains were in a standing-up phase and scanning tunneling microscopy (STM) showed that their molecular organization within about 5 nm, 40 nm, 50 nm and 120 nm domains, was dependent upon the size of the domain, such that structure of the C5DT transitions from (?3 * ?3) R30 degrees , to (2 * 2), and ultimately to a disordered phase with increasing domain size. This is due to the varying degrees of influence of the surrounding C12; providing sufficient van der Waals interactions as well as a geometric confinement to stabilize the standing-up phase of the C5DT. Understanding the molecular configuration of dithiol SAMs affords their use as a reactive template to subsequently bind active head groups. As a proof of principle, porphyrins with a pendant pentafluorophenyl ring were attached to the C5DT domains by a 'click' reaction between the fluorinated ring and the free thiol on the surface. From AFM and STM, these porphyrin derivatives reacted selectively with the C5DT domains with some porphyrins binding directly to the C5DT, subsequently allowing additional localized porphyrin deposition through pi-stacking. PMID- 26872126 TI - Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARgamma Signaling. AB - BACKGROUND/AIMS: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. METHODS: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. RESULTS: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARgamma expression and activity, respectively. Most importantly, the PPARgamma-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARgamma in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARgamma promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARgamma signaling in macrophages. CONCLUSION: These results demonstrate that macrophage CGI-58 enhances PPARgamma signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction. PMID- 26872127 TI - Analysis of bacterial community profiles of endodontically infected primary teeth using pyrosequencing. AB - OBJECTIVE: The purpose of this study was to identify the endodontic microbiome in primary teeth with dental caries using high-throughput pyrosequencing and to establish data on the oral microbiome of primary teeth with endodontic infection. METHODS: Ten primary teeth with dental caries and endodontic infection were included. Samples were collected from root canals using sterilized paper points and analyzed by pyrosequencing, based on the V1-V3 hypervariable region of the 16S rRNA gene. The data were analyzed using the CLcommunity software. RESULTS: Analysis of the 10 samples yielded a total of 64,291 16S rRNA gene sequences. In total, 1586 OTUs (range, 91-235), six bacterial phyla, including unclassified, and 187 genera were assigned. At the genus level, Neisseria (group A), Acinetobacter (group B), and Fusobacterium (group C) were prominent. These predominant microorganisms were associated with the clinical condition and reflected the progression of endodontic infection in primary teeth. CONCLUSIONS: This study revealed a relationship between the oral microbiome and endodontic infection in primary teeth. Additionally, anaerobic bacteria such as Fusobacterium species were dominant in the teeth with apical abscesses. PMID- 26872128 TI - Surgical Debridement Is Superior to Sole Antibiotic Therapy in a Novel Murine Posttraumatic Osteomyelitis Model. AB - INTRODUCTION: Bone infections after trauma, i.e. posttraumatic osteomyelitis, pose one of the biggest problems of orthopedic surgery. Even after sufficient clinical therapy including vast debridement of infected bone and antibiotic treatment, regeneration of postinfectious bone seems to be restricted. One explanation includes the large sized defects resulting from sufficient debridement. Furthermore, it remains unclear if inflammatory processes after bone infection do affect bone regeneration. For continuing studies in this field, an animal model is needed where bone regeneration after sufficient treatment can be studied in detail. METHODS: For this purpose we created a stable infection in murine tibiae by Staphylococcus aureus inoculation. Thereafter, osteomyelitic bones were debrided thoroughly and animals were subsequently treated with antibiotics. Controls included debrided, non-infected, as well as infected animals exclusively treated with antibiotics. To verify sufficient treatment of infected bone, different assessments detecting S. aureus were utilized: agar plates, histology and RT-qPCR. RESULTS: All three detection methods revealed massive reduction or eradication of S. aureus within debrided bones 1 and 2 weeks postoperatively, whereas sole antibiotic therapy could not provide sufficient treatment of osteomyelitic bones. Debrided, previously infected bones showed significantly decreased bone formation, compared to debrided, non-infected controls. DISCUSSION: Thus, the animal model presented herein provides a reliable and fascinating tool to study posttraumatic osteomyelitis for clinical therapies. PMID- 26872129 TI - A Computational Cognitive Biomarker for Early-Stage Huntington's Disease. AB - Huntington's disease (HD) is genetically determined but with variability in symptom onset, leading to uncertainty as to when pharmacological intervention should be initiated. Here we take a computational approach based on neurocognitive phenotyping, computational modeling, and classification, in an effort to provide quantitative predictors of HD before symptom onset. A large sample of subjects-consisting of both pre-manifest individuals carrying the HD mutation (pre-HD), and early symptomatic-as well as healthy controls performed the antisaccade conflict task, which requires executive control and response inhibition. While symptomatic HD subjects differed substantially from controls in behavioral measures [reaction time (RT) and error rates], there was no such clear behavioral differences in pre-HD. RT distributions and error rates were fit with an accumulator-based model which summarizes the computational processes involved and which are related to identified mechanisms in more detailed neural models of prefrontal cortex and basal ganglia. Classification based on fitted model parameters revealed a key parameter related to executive control differentiated pre-HD from controls, whereas the response inhibition parameter declined only after symptom onset. These findings demonstrate the utility of computational approaches for classification and prediction of brain disorders, and provide clues as to the underlying neural mechanisms. PMID- 26872130 TI - Centering the Organizing Center in the Arabidopsis thaliana Shoot Apical Meristem by a Combination of Cytokinin Signaling and Self-Organization. AB - Plants have the ability to continously generate new organs by maintaining populations of stem cells throught their lives. The shoot apical meristem (SAM) provides a stable environment for the maintenance of stem cells. All cells inside the SAM divide, yet boundaries and patterns are maintained. Experimental evidence indicates that patterning is independent of cell lineage, thus a dynamic self regulatory mechanism is required. A pivotal role in the organization of the SAM is played by the WUSCHEL gene (WUS). An important question in this regard is that how WUS expression is positioned in the SAM via a cell-lineage independent signaling mechanism. In this study we demonstrate via mathematical modeling that a combination of an inhibitor of the Cytokinin (CK) receptor, Arabidopsis histidine kinase 4 (AHK4) and two morphogens originating from the top cell layer, can plausibly account for the cell lineage-independent centering of WUS expression within SAM. Furthermore, our laser ablation and microsurgical experiments support the hypothesis that patterning in SAM occurs at the level of CK reception and signaling. The model suggests that the interplay between CK signaling, WUS/CLV feedback loop and boundary signals can account for positioning of the WUS expression, and provides directions for further experimental investigation. PMID- 26872131 TI - Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection. AB - BACKGROUND: The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. METHODS: A prospective multicenter study (GENDRES network) was conducted between 2011-2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. RESULTS: 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). CONCLUSION: Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases. PMID- 26872132 TI - Thymoquinone Rescues T Lymphocytes from Gamma Irradiation-Induced Apoptosis and Exhaustion by Modulating Pro-Inflammatory Cytokine Levels and PD-1, Bax, and Bcl 2 Signaling. AB - BACKGROUND/AIMS: Recent studies have shown that thymoquinone (TQ) exerts protective effects against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats. Nevertheless, there is no published work investigated the effects of TQ on T cell development and biology in animal models exposed to gamma radiation. Therefore, in the present study we focused on determining the effects of TQ on radiation damage in the thymus, radiation induced T cell imbalance, and on immune dysfunction induced by gamma-rays. METHODS: Three groups of rats were used: a control group, a gamma-irradiated group, and a gamma-irradiated group that was orally supplemented with TQ. Serum lipid profiles, malondialdehyde (MDA) levels, and pro-inflammatory cytokine levels were measured to assess gamma irradiation-induced oxidative stress and inflammatory capacity. T cell apoptosis was evaluated by annexin V/propidium iodide staining followed by flow cytometry analysis. The expression of pro apoptotic proteins such as Bax and caspase-3, the anti-apoptotic protein Bcl-2, and an exhaustion marker of T cells (PD-1) in CD4+ and CD8+ T cell populations was evaluated using flow cytometry analysis. The T cell architecture of the thymus gland was evaluated by histological analysis. RESULTS: Exposure to gamma radiation increased triglyceride, cholesterol, LDL-C, MDA, TNF-alpha and IL-6 levels and decreased HDL-C levels. The altered lipid profile and MDA and pro inflammatory cytokine (TNF-alpha and IL-6) levels induced by exposure to gamma radiation were significantly restored in TQ-treated gamma-irradiated rats. Rats exposed to gamma radiation exhibited increased exhaustion of T lymphocytes via down-regulation of Bcl-2 expression and upregulation of PD-1, Bax, and caspase-3 expression, which sensitized these cells to apoptosis. Interestingly, treatment of gamma-irradiated rats with TQ decreased T cell exhaustion and apoptosis by modulating the expression of Bcl-2, PD-1, Bax, and caspase-3. CONCLUSIONS: Our results provide evidence for the beneficial effects of TQ as an effective radioprotective candidate that enhances cellular immunity. PMID- 26872133 TI - Effect of Evodiamine on CYP Enzymes in Rats by a Cocktail Method. AB - The aim of this study was to assess the influence of evodiamine on the activities of the drug-metabolizing enzymes cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 in rats. The activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 were measured using specific probe drugs. After pretreatment for 1 week with evodiamine or physiological saline (control group) by oral administration, probe drugs phenacetin (5.0 mg/kg; CYP1A2 activity), tolbutamide (1.0 mg/kg; CYP2C9 activity), omeprazole (10 mg/kg; CYP2C19 activity), metoprolol (20 mg/kg; CYP2D6 activity) and midazolam (10 mg/kg; CYP3A4 activity) were administered to rats by oral administration. The blood was then collected at different times for ultra-performance liquid chromatography-tandem mass spectrometry analysis. The data showed that evodiamine exhibits an inhibitory effect on CYP1A2, CYP2C9 and CYP2D6 by increasing t(1/2), Cmax and AUC(0-infinity), and decreasing CL/F compared with those of the control group. However, no significant changes in CYP2C19 and CYP3A4 activities were observed. In conclusion, the results indicated that evodiamine could inhibit CYP1A2, CYP2C9 and CYP2D6, which may affect the disposition of medicines primarily dependent on these pathways. Our work may be the basis of related herb-drug interactions in the clinic. PMID- 26872135 TI - Correction: Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF Mediated Tissue Pathology. PMID- 26872136 TI - Do Not Divide Count Data with Count Data; A Story from Pollination Ecology with Implications Beyond. AB - Studies in ecology are often describing observed variations in a certain ecological phenomenon by use of environmental explanatory variables. A common problem is that the numerical nature of the ecological phenomenon does not always fit the assumptions underlying traditional statistical tests. A text book example comes from pollination ecology where flower visits are normally reported as frequencies; number of visits per flower per unit time. Using visitation frequencies in statistical analyses comes with two major caveats: the lack of knowledge on its error distribution and that it does not include all information found in the data; 10 flower visits in 20 flowers is treated the same as recording 100 visits in 200 flowers. We simulated datasets with various "flower visitation distributions" over various numbers of flowers observed (exposure) and with different types of effects inducing variation in the data. The different datasets were then analyzed first with the traditional approach using number of visits per flower and then by using count data models. The analysis of count data gave a much better chance of detecting effects than the traditionally used frequency approach. We conclude that if the data structure, statistical analyses and interpretations of results are mixed up, valuable information can be lost. PMID- 26872134 TI - A Microfluidic Channel Method for Rapid Drug-Susceptibility Testing of Pseudomonas aeruginosa. AB - The recent global increase in the prevalence of antibiotic-resistant bacteria and lack of development of new therapeutic agents emphasize the importance of selecting appropriate antimicrobials for the treatment of infections. However, to date, the development of completely accelerated drug susceptibility testing methods has not been achieved despite the availability of a rapid identification method. We proposed an innovative rapid method for drug susceptibility testing for Pseudomonas aeruginosa that provides results within 3 h. The drug susceptibility testing microfluidic (DSTM) device was prepared using soft lithography. It consisted of five sets of four microfluidic channels sharing one inlet slot, and the four channels are gathered in a small area, permitting simultaneous microscopic observation. Antimicrobials were pre-introduced into each channel and dried before use. Bacterial suspensions in cation-adjusted Mueller-Hinton broth were introduced from the inlet slot and incubated for 3 h. Susceptibilities were microscopically evaluated on the basis of differences in cell numbers and shapes between drug-treated and control cells, using dedicated software. The results of 101 clinically isolated strains of P. aeruginosa obtained using the DSTM method strongly correlated with results obtained using the ordinary microbroth dilution method. Ciprofloxacin, meropenem, ceftazidime, and piperacillin caused elongation in susceptible cells, while meropenem also induced spheroplast and bulge formation. Morphological observation could alternatively be used to determine the susceptibility of P. aeruginosa to these drugs, although amikacin had little effect on cell shape. The rapid determination of bacterial drug susceptibility using the DSTM method could also be applicable to other pathogenic species, and it could easily be introduced into clinical laboratories without the need for expensive instrumentation. PMID- 26872137 TI - Phytochemical Screening, Antidepressant and Analgesic Effects of Aqueous Extract of Anethum graveolens L. From Southeast of Morocco. AB - This study aims to investigate the antidepressant and analgesic properties of the aqueous extract of Anethum graveolens L. from South of Morocco (Rissani Errachidia region). Extract of plant is obtained by aqueous decoction and administered to Wistar rats orally. The extract has a significant antidepressant and analgesic effects compared with the drug references (sertraline and tramadol) without any adverse effects. The dose of 250 mg/kg, body weight shows the best antidepressant and analgesic effects than 1 g/kg, body weight. Phytochemical study of the aqueous extract of the plant has to show its highlight in polyphenols, flavonoids, and tannins. PMID- 26872138 TI - Comparison of Haploidentical Hematopoietic Stem Cell Transplantation and Immunosuppressive Therapy for the Treatment of Acquired Severe Aplastic Anemia in Pediatric Patients. AB - This study aimed to compare the efficacy and safety between haploidentical hematopoietic stem cell transplantation (HHCT) and immunosuppressive therapy (IST) for the treatment of pediatric acquired severe aplastic anemia (SAA). The clinical data of 28 children with SAA treated from June 2010 to October 2014 at our hospital were retrospectively reviewed. Of these patients, 18 were treated with HHCT and 10 with IST. The median follow-up time was 23.5 months (range, 3-52 months). There was no significant difference in overall survival rate between the HHCT group and the IST group (66.7% vs. 70%, P > 0.05). Graft-versus-host disease occurred in 83.3% (15/18) of the HHCT group, including 5 cases with grade III or higher. In comparison with IST, HHCT has similar efficacy and safety profiles in the treatment of pediatric SAA. PMID- 26872139 TI - A Topical Medication of All-Trans Retinoic Acid Reduces Sebum Excretion Rate in Patients With Forehead Acne. AB - Acne is a disease of the hair follicles of the face, chest, and back that affects almost all teenagers during puberty. This study is conducted to investigate if all-trans retinoic acid (ATRA) could reduce sebum excretion rate (SER) in acne patients by influencing content of skin-surface lipid production. Thirty-nine patients with forehead acne were topically treated with cream base (vehicle) and 0.025% ATRA cream once a night for 7 days. Separation and identification of sebum production collected from the skin on the acne were performed using thin-layer chromatography. SER was calculated according to the total amount of individual sebum productions that were quantified by using Alphaimager IS-2200 imaging analysis. Our data showed that the value of SER on the acne-affected skin was significantly decreased in the ATRA-treated patients as compared with ones treated with vehicle (P < 0.01). Treatment with ATRA resulted in inducing significant decreases in the contents of wax esters (WE), triglycerides and fatty acids, and free fatty acids (FFA) productions (all P < 0.01). In further analysis, the changes in the data before and after treatments with vehicle and ATRA were compared with significant differences exhibited in the values of SER, WE, and FFA (all P < 0.05). This study indicates that the topical application of ATRA in treatment of acne patients induces decrease in SER by inhibiting the excretion of WE and FFA productions. PMID- 26872140 TI - Development of Antibiotic Resistance during Simulated Treatment of Pseudomonas aeruginosa in Chemostats. AB - During treatment of infections with antibiotics in critically ill patients in the intensive care resistance often develops. This study aims to establish whether under those conditions this resistance can develop de novo or that genetic exchange between bacteria is by necessity involved. Chemostat cultures of Pseudomonas aeruginosa were exposed to treatment regimes with ceftazidime and meropenem that simulated conditions expected in patient plasma. Development of antibiotic resistance was monitored and mutations in resistance genes were searched for by sequencing PCR products. Even at the highest concentrations that can be expected in patients, sufficient bacteria survived in clumps of filamentous cells to recover and grow out after 3 to 5 days. At the end of a 7 days simulated treatment, the minimal inhibitory concentration (MIC) had increased by a factor between 10 and 10,000 depending on the antibiotic and the treatment protocol. The fitness costs of resistance were minimal. In the resistant strains, only three mutations were observed in genes associated with beta-lactam resistance. The development of resistance often observed during patient treatment can be explained by de novo acquisition of resistance and genetic exchange of resistance genes is not by necessity involved. As far as conclusions based on an in vitro study using P. aeruginosa and only two antibiotics can be generalized, it seems that development of resistance can be minimized by treating with antibiotics in the highest concentration the patient can endure for the shortest time needed to eliminate the infection. PMID- 26872141 TI - Prevention of laryngospasm with rocuronium in cats: a dose-finding study. AB - OBJECTIVE: To identify the dose of rocuronium that will prevent a laryngeal response to water spraying of the glottis in anesthetized cats. STUDY DESIGN: Randomized crossover study. ANIMALS: Eight healthy, adult, short-haired cats, aged 1-4 years, weighing 3.2-6.0 kg. METHODS: Each cat was anesthetized four times and administered one of four doses of rocuronium (0.1, 0.2, 0.3 and 0.6 mg kg(-1) ) in random order. The larynx was observed with a video-endoscope inserted through a laryngeal mask airway. Video-clips of the laryngeal response to a sterile water spray (0.2 mL) were obtained at baseline (without rocuronium) and at maximal effect of each treatment. Glottal closure score (0-2), duration of glottal closure, and number of adductive arytenoid movements were obtained from video-clips of laryngeal responses (reproduced in slow motion) at baseline and after treatment. Two observers blinded to treatment allocation scored the vigor of the laryngeal response on a visual analog scale (VAS). The duration of apnea (up to 5 minutes) was recorded for each treatment. RESULTS: Compared with baseline, rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) significantly decreased all glottal scores obtained from the videos (all p < 0.03). Both observers gave lower VAS scores after 0.3 mg kg(-1) (both p = 0.015). Apnea lasting >= 5 minutes occurred in none, one, three and seven of eight cats administered doses of rocuronium 0.1, 0.2, 0.3 and 0.6 mg kg(-1) , respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) consistently decreased the completeness and duration of the laryngeal response to water spray, and reduced the number of arytenoid adductive movements in response to that stimulus. However, a laryngeal response was never completely prevented. Rocuronium 0.3 mg kg(-1) may be useful for facilitating tracheal intubation. Positive pressure ventilation must be available for cats administered rocuronium. PMID- 26872142 TI - Neighborhood Regularized Logistic Matrix Factorization for Drug-Target Interaction Prediction. AB - In pharmaceutical sciences, a crucial step of the drug discovery process is the identification of drug-target interactions. However, only a small portion of the drug-target interactions have been experimentally validated, as the experimental validation is laborious and costly. To improve the drug discovery efficiency, there is a great need for the development of accurate computational approaches that can predict potential drug-target interactions to direct the experimental verification. In this paper, we propose a novel drug-target interaction prediction algorithm, namely neighborhood regularized logistic matrix factorization (NRLMF). Specifically, the proposed NRLMF method focuses on modeling the probability that a drug would interact with a target by logistic matrix factorization, where the properties of drugs and targets are represented by drug-specific and target-specific latent vectors, respectively. Moreover, NRLMF assigns higher importance levels to positive observations (i.e., the observed interacting drug-target pairs) than negative observations (i.e., the unknown pairs). Because the positive observations are already experimentally verified, they are usually more trustworthy. Furthermore, the local structure of the drug-target interaction data has also been exploited via neighborhood regularization to achieve better prediction accuracy. We conducted extensive experiments over four benchmark datasets, and NRLMF demonstrated its effectiveness compared with five state-of-the-art approaches. PMID- 26872143 TI - Metagenomic Sequencing of the Chronic Obstructive Pulmonary Disease Upper Bronchial Tract Microbiome Reveals Functional Changes Associated with Disease Severity. AB - Chronic Obstructive Pulmonary Disease (COPD) is a major source of mortality and morbidity worldwide. The microbiome associated with this disease may be an important component of the disease, though studies to date have been based on sequencing of the 16S rRNA gene, and have revealed unequivocal results. Here, we employed metagenomic sequencing of the upper bronchial tract (UBT) microbiome to allow for greater elucidation of its taxonomic composition, and revealing functional changes associated with the disease. The bacterial metagenomes within sputum samples from eight COPD patients and ten 'healthy' smokers (Controls) were sequenced, and suggested significant changes in the abundance of bacterial species, particularly within the Streptococcus genus. The functional capacity of the COPD UBT microbiome indicated an increased capacity for bacterial growth, which could be an important feature in bacterial-associated acute exacerbations. Regression analyses correlated COPD severity (FEV1% of predicted) with differences in the abundance of Streptococcus pneumoniae and functional classifications related to a reduced capacity for bacterial sialic acid metabolism. This study suggests that the COPD UBT microbiome could be used in patient risk stratification and in identifying novel monitoring and treatment methods, but study of a longitudinal cohort will be required to unequivocally relate these features of the microbiome with COPD severity. PMID- 26872144 TI - Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate? AB - BACKGROUND: Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF. METHODS: This retrospective, single center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy. RESULTS: Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(+/-11.8) years; median [IQR] TDF duration was 3.3 years. [1.5-7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/MUL [267.5-721.5] and 62 copies/mL [0-40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2-14.0; p = 0.024). CONCLUSION: Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients. PMID- 26872146 TI - A Feature Selection Algorithm to Compute Gene Centric Methylation from Probe Level Methylation Data. AB - DNA methylation is an important epigenetic event that effects gene expression during development and various diseases such as cancer. Understanding the mechanism of action of DNA methylation is important for downstream analysis. In the Illumina Infinium HumanMethylation 450K array, there are tens of probes associated with each gene. Given methylation intensities of all these probes, it is necessary to compute which of these probes are most representative of the gene centric methylation level. In this study, we developed a feature selection algorithm based on sequential forward selection that utilized different classification methods to compute gene centric DNA methylation using probe level DNA methylation data. We compared our algorithm to other feature selection algorithms such as support vector machines with recursive feature elimination, genetic algorithms and ReliefF. We evaluated all methods based on the predictive power of selected probes on their mRNA expression levels and found that a K Nearest Neighbors classification using the sequential forward selection algorithm performed better than other algorithms based on all metrics. We also observed that transcriptional activities of certain genes were more sensitive to DNA methylation changes than transcriptional activities of other genes. Our algorithm was able to predict the expression of those genes with high accuracy using only DNA methylation data. Our results also showed that those DNA methylation sensitive genes were enriched in Gene Ontology terms related to the regulation of various biological processes. PMID- 26872147 TI - Distinguishing morphology of reactive versus abnormal neoplastic peripheral blood lymphocytosis. Challenges illustrated by two proficiency testing surveys. PMID- 26872149 TI - Correction: Seeing Minds in Others - Can Agents with Robotic Appearance Have Human-Like Preferences? PMID- 26872145 TI - Fibroblast Growth Factor 21 (FGF21) Protects against High Fat Diet Induced Inflammation and Islet Hyperplasia in Pancreas. AB - Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue. In order to understand the physiology of FGF21 in the pancreas, we analyzed its expression and regulation in both acinar and islet tissues. We found that acinar tissue express 20-fold higher levels than that observed in islets. We also observed that pancreatic FGF21 is nutritionally regulated; a marked reduction in FGF21 expression was noted with fasting while obesity is associated with 3-4 fold higher expression. Acinar and islet cells are targets of FGF21, which when systemically administered, leads to phosphorylation of the downstream target ERK 1/2 in about half of acinar cells and a small subset of islet cells. Chronic, systemic FGF21 infusion down-regulates its own expression in the pancreas. Mice lacking FGF21 develop significant islet hyperplasia and periductal lymphocytic inflammation when fed with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased levels of inflammatory cells were coupled with elevated expression of cytokines such as TNFalpha, IFNgamma and IL1beta. We conclude that FGF21 acts to limit islet hyperplasia and may also prevent pancreatic inflammation. PMID- 26872148 TI - Atrial Anti-Arrhythmic Effects of Heptanol in Langendorff-Perfused Mouse Hearts. AB - Acute effects of heptanol (0.1 to 2 mM) on atrial electrophysiology were explored in Langendorff-perfused mouse hearts. Left atrial bipolar electrogram or monophasic action potential recordings were obtained during right atrial stimulation. Regular pacing at 8 Hz elicited atrial activity in 11 out of 11 hearts without inducing atrial arrhythmias. Programmed electrical stimulation using a S1S2 protocol provoked atrial tachy-arrhythmias in 9 of 17 hearts. In the initially arrhythmic group, 2 mM heptanol exerted anti-arrhythmic effects (Fisher's exact test, P < 0.05) and increased atrial effective refractory period (ERP) from 26.0 +/- 1.9 to 57.1 +/- 2.5 ms (ANOVA, P < 0.001) despite increasing activation latency from 18.7 +/- 1.1 to 28.9 +/- 2.1 ms (P < 0.001) and leaving action potential duration at 90% repolarization (APD90) unaltered (25.6 +/- 1.2 vs. 27.2 +/- 1.2 ms; P > 0.05), which led to increases in ERP/latency ratio from 1.4 +/- 0.1 to 2.1 +/- 0.2 and ERP/APD90 ratio from 1.0 +/- 0.1 to 2.1 +/- 0.2 (P < 0.001). In contrast, in the initially non-arrhythmic group, heptanol did not alter arrhythmogenicity, increased AERP from 47.3 +/- 5.3 to 54.5 +/- 3.1 ms (P < 0.05) and activation latency from 23.7 +/- 2.2 to 31.3 +/- 2.5 ms and did not alter APD90 (24.1 +/- 1.2 vs. 25.0 +/- 2.3 ms; P > 0.05), leaving both AERP/latency ratio (2.1 +/- 0.3 vs. 1.9 +/- 0.2; P > 0.05) and ERP/APD90 ratio (2.0 +/- 0.2 vs. 2.1 +/- 0.1; P > 0.05) unaltered. Lower heptanol concentrations (0.1, 0.5 and 1 mM) did not alter arrhythmogenicity or the above parameters. The present findings contrast with known ventricular pro-arrhythmic effects of heptanol associated with decreased ERP/latency ratio, despite increased ERP/APD ratio observed in both the atria and ventricles. PMID- 26872150 TI - Physical and Physiological Characteristics of Various-Sided Games in Elite Women's Soccer. AB - PURPOSE: To investigate the physical and physiological response to different formats of various-sided games. METHODS: Eighteen elite women's soccer players wore 15-Hz global positioning system devices and heart-rate (HR) monitors during various-sided games (small, 4 vs 4 and 5 vs 5; medium, 6 vs 6 and 7 vs 7; large, 8 vs 8 and 9 vs 9). RESULTS: Players covered more relative sprinting distance during large-sided games than in small-sided (P < .001, d = 0.69) and medium sided (P < .001, d = 0.54) games. In addition, a greater proportion of total acceleration efforts that had a commencement velocity <1 m/s were observed in small-sided games (44.7% +/- 5.5%) than in large-sided games (36.7% +/- 10.6%) (P = .018, d = 0.94). This was accompanied by a greater proportion of acceleration efforts with a final velocity equivalent to the sprint threshold in large-sided games (15.4% +/- 7.7%) than in small-sided games (5.2% +/- 2.5%) (P < .001, d = 1.78). The proportion of time spent in HR zone 4 (>85% maximum HR) was greater during small-sided games (69.8% +/- 2.5%) than in medium- (62.1% +/- 2.8%, d = 2.90) and large-sided games (54.9% +/- 3.1%) (P < .001, d = 5.29). CONCLUSIONS: The results from this study demonstrate that coaches can use small-sided games as an aerobic conditioning stimulus and to develop players' explosiveness and repeat sprint ability over short durations. Large-sided games can be used to maintain aerobic capacity and develop maximum speed over longer distances. PMID- 26872151 TI - A case of Stage IA classical Hodgkin lymphoma with FDG-avid tonsils. PMID- 26872152 TI - Morphing Metal and Elastomer Bicontinuous Foams for Reversible Stiffness, Shape Memory, and Self-Healing Soft Machines. AB - A metal-elastomer-foam composite that varies in stiffness, that can change shape and store shape memory, that self-heals, and that welds into monolithic structures from smaller components is presented. PMID- 26872153 TI - Promoting nuclear energy to sustain biodiversity conservation in the face of climate change: response to Brook and Bradshaw 2015. PMID- 26872156 TI - High-power temperature-stable GaInNAs distributed Bragg reflector laser emitting at 1180 nm. AB - We report a single-mode 1180 nm distributed Bragg reflector (DBR) laser diode with a high output power of 340 mW. For the fabrication, we employed novel nanoimprint lithography that ensures cost-effective, large-area, conformal patterning and does not require regrowth. The output characteristics exhibited outstanding temperature insensitivity with a power drop of only 30% for an increase of the mount temperature from 20 degrees C to 80 degrees C. The high temperature stability was achieved by using GaInNAs/GaAs quantum wells (QWs), which exhibit improved carrier confinement compared to standard InGaAs/GaAs QWs. The corresponding characteristic temperatures were T0=110 K and T1=160 K. Moreover, we used a large detuning between the peak wavelength of the material gain at room temperature and the lasing wavelength determined by the DBR. In addition to good temperature characteristics, GaInNAs/GaAs QWs exhibit relatively low lattice strain with direct impact on improving the lifetime of laser diodes at this challenging wavelength range. The single-mode laser emission could be tuned by changing the mount temperature (0.1 nm/ degrees C) or the drive current (0.5 pm/mA). The laser showed no degradation in a room-temperature lifetime test at 900 mA drive current. These compact and efficient 1180 nm laser diodes are instrumental for the development of compact frequency-doubled yellow-orange lasers, which have important applications in medicine and spectroscopy. PMID- 26872157 TI - Ultralow threshold optical bistability in metal/randomly layered media structure. AB - The Tamm plasmon polaritons (TPPs) at the metal/randomly layered media (RLM) structure were studied. The optical bistability was realized by replacing one of the RLM components of the Kerr nonlinear material. An ultralow switching threshold of 44 kW/cm2 was obtained, due to the field enhancement through the resonant transmission in the RLM and TPPs. A theoretical analysis was presented, matching the numerical simulation result well. The bistability threshold was found to be related to the mismatch in the excitation frequency of TPPs, the thickness of metal film, and the intensity of nonlinear response. PMID- 26872155 TI - Enzymatic removal of N-glycans by PNGase F coated magnetic microparticles. AB - Investigation of protein glycosylation is an important area in biomarker discovery and biopharmaceutical research. Alterations in protein N-glycosylation can be an indication of changes in pathological conditions in the medical field or production parameters of biotherapeutics. Rapid development of these disciplines calls for fast, high-throughput, and reproducible methods to analyze protein N-glycosylation. Currently used methods require either long deglycosylation times or large excess of enzymes. In this paper, we report on the use of PNGase F immobilization onto the surface of magnetic microparticles and their use in rapid and efficient removal of N-glycans from glycoproteins. The use of immobilized PNGase F also allowed reusability of the enzyme-coated beads as the magnetic microparticles can be readily partitioned from the sample by a magnet after each deglycosylation reaction. The efficiency and activity of the PNGase F coated magnetic beads was compared with in-solution enzyme reactions using standard glycoproteins possessing the major N-glycan types of neutral, high mannose, and highly sialylated carbohydrates. The PNGase F coated magnetic beads offered comparable deglycosylation level to the conventional in-solution based method in 10-min reaction times for the model glycoproteins of immunoglobulin G (mostly neutral carbohydrates), ribonuclease B (high mannose type sugars), and fetuin (highly sialylated oligosaccharides) with the special features of easy removal of the enzyme from the reaction mixture and reusability. PMID- 26872158 TI - Swept source digital holographic phase microscopy. AB - We propose a swept source-based digital holographic phase microscopy technique. By scanning source wavelength, a series of on-axis interferograms can be obtained for accurate determination of the sample phase using spectral domain interferometry. With these sample spectra, sources of undesirable interference artifacts, often significant in holographic systems, can be identified and avoided by placing the sample signal at a spectral frequency with a clean background. Pathlength sensitivity better than 0.3 nm can, thus, be achieved. The quantitative pathlength image of live sperm cells is obtained with clear identification of morphological features. In addition, the availability of sample spectrum also permits the retrieval of its spectroscopic information. The wavelength-dependent refractive indices of indocyanine green solution are obtained to demonstrate this capability. PMID- 26872159 TI - Removal of Rb(6(2)P) by H(2), CH(4), and C(2)H(6). AB - The saturated hydrocarbons methane and ethane are often used as collisional energy transfer agents in diode-pumped alkali vapor lasers (DPALs). Problems are encountered because the hydrocarbons eventually react with the optically pumped alkali atoms, resulting in the contamination of the gas lasing medium and damage of the gas cell windows. The reactions require excitation of the more highly excited states of the alkali atoms, which can be generated in DPAL systems by energy pooling processes. Knowledge of the production and loss rates for the higher excited states is needed for a quantitative understanding of the photochemistry. In the present study, we have used experimental and theoretical techniques to characterize the removal of Rb(6P2) by hydrogen, methane, and ethane. PMID- 26872154 TI - Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants. AB - BACKGROUND: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children. METHODS: A case cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed. FINDINGS: Median age at 25 hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV infected and 26% had low 25-hydroxyvitamin D (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01-3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03-3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs. CONCLUSIONS: Two novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child's risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT00080119. PMID- 26872160 TI - Real-time fluorescence lifetime actuation for cell sorting using a CMOS SPAD silicon photomultiplier. AB - Time-correlated single photon counting (TCSPC) is a fundamental fluorescence lifetime measurement technique offering high signal to noise ratio (SNR). However, its requirement for complex software algorithms for histogram processing restricts throughput in flow cytometers and prevents on-the-fly sorting of cells. We present a single-point digital silicon photomultiplier (SiPM) detector accomplishing real-time fluorescence lifetime-activated actuation targeting cell sorting applications in flow cytometry. The sensor also achieves burst-integrated fluorescence lifetime (BIFL) detection by TCSPC. The SiPM is a single-chip complementary metal-oxide-semiconductor (CMOS) sensor employing a 32*32 single photon avalanche diode (SPAD) array and eight pairs of time-interleaved time to digital converters (TI-TDCs) with a 50 ps minimum timing resolution. The sensor's pile-up resistant embedded center of mass method (CMM) processor accomplishes low latency measurement and thresholding of fluorescence lifetime. A digital control signal is generated with a 16.6 MUs latency for cell sorter actuation allowing a maximum cell throughput of 60,000 cells per second and an error rate of 0.6%. PMID- 26872161 TI - All optical signal level swapping and multilevel amplitude noise mitigation based on different regions of optical parametric amplification. AB - All optical signal level swapping and multilevel amplitude noise mitigation are experimentally demonstrated using the three gain regions of optical parametric amplification, i.e., linear, saturation, and inversion. The two-amplitude-shift keying and eight-quadrature-amplitude-modulation optical communication systems with baud rates of both 10 and 20 Gbaud have been employed to demonstrate the proposed approaches. Less than 1% error-vector-magnitude degradation is observed after signal level swapping. For amplitude noise mitigation, a more than 20% decrease in amplitude error is confirmed. PMID- 26872162 TI - Loss induced amplification of graphene plasmons. AB - This Letter introduces a new mechanism to reverse and control the effect of losses in the plasmonic systems by using a coupled parity-time symmetric graphene waveguide with complex potentials. In order to explore the uncharted properties of parity-time symmetric graphene plasmons, this Letter analytically shows the plasmonic parity-time symmetry breaking in the coupled graphene waveguide by Sommerfeld integration. This phase transition leads to the distinct spatial propagation behaviors of graphene plasmons in the exact or broken parity-time symmetric phase driven by a point source. Particularly, a loss induced plasmonic amplification, as a characteristic of exceptional point behavior, is for the first time, to the best of our knowledge, revealed in the realm of graphene plasmonics. PMID- 26872163 TI - Transparent ultraviolet photovoltaic cells. AB - Photovoltaic cells have been fabricated from p-GaN/MgO/n-ZnO structures. The photovoltaic cells are transparent to visible light and can transform ultraviolet irradiation into electrical signals. The efficiency of the photovoltaic cells is 0.025% under simulated AM 1.5 illumination conditions, while it can reach 0.46% under UV illumination. By connecting several such photovoltaic cells in a series, light-emitting devices can be lighting. The photovoltaic cells reported in this Letter may promise the applications in glass of buildings to prevent UV irradiation and produce power for household appliances in the future. PMID- 26872164 TI - Measured photoemission from electron wave packets in a strong laser field. AB - We present calibrated measurements of single-photon Thomson scattering from free electrons driven by a laser with intensity 1018 W/cm2. The measurements demonstrate that individual electrons radiate with the strength of point emitters, even when their wave packets spread to the scale of the driving laser wavelength. The result agrees with predictions of quantum electrodynamics. PMID- 26872165 TI - In-fiber reconfigurable generation of arbitrary (asymmetric) picosecond temporal intensity waveforms by time-domain optical pulse shaping. AB - A fiber-optic programmable optical pulse shaper is experimentally demonstrated using multi-level phase-only linear filtering, capable of synthesizing arbitrary (including asymmetric) temporal intensity waveforms. The reconfigurable filtering operation is implemented in the time domain with a single electro-optic phase modulator (EO-PM) driven by a high-speed electronic arbitrary waveform generator (AWG). The required multi-level modulation signal is calculated from a combination of optimization algorithms, namely the Gerchberg-Saxton algorithm (GSA) and a genetic algorithm (GA). We report the synthesis of high-quality, arbitrary temporal intensity profiles, including asymmetric triangular waveforms and ~150 Gbaud random on-off keying (OOK) pulse and pulse amplitude-modulation (PAM) code sequences, with a temporal resolution of ~2 ps over a maximum time window of ~60 ps. PMID- 26872166 TI - Theoretical scheme for simultaneously observing forward-backward photoelectron holography. AB - Photoelectron angular momentum distribution of He+ driven by a few cycle laser is investigated numerically. We simultaneously observe two dominant interference patterns with one shot of lasers by solving the 3D time-dependent Schrodinger equation. Analysis of a semiclassical model identifies these two interference patterns as two types of photoelectron holography. The interference pattern with Pz>0 is a type of forward rescattering holography, which comes from the interference between direct (reference) and rescattered (signal) forward electrons ionized in the same quarter-cycle. The interference pattern with Pz<0 is a type of backward rescattering holography, which comes from the interference between a direct electron ionized in the third quarter cycle and rescattered backward electron ionized in the first quarter-cycle. Moreover, we propose a method to distinguish this backward rescattering holography and intracycle interference patterns of direct electrons. PMID- 26872167 TI - High reflectance Cr/V multilayer with B(4)C barrier layer for water window wavelength region. AB - To develop the high reflectance mirror for the short wavelength range of the water window region (lambda=2.42-2.73 nm), Cr/V multilayers with B4C barrier layers are studied. The grazing incidence x-ray reflectometry results show that the multilayer interface widths are significantly reduced down to 0.21 0.31 nm, after the introduction of 0.1 nm B4C barrier layers at both interfaces. The [B4C/Cr/B4C/V] multilayer with a large number of bilayers of N=300 maintains the same small interface widths while the surface roughness is only 0.2 nm. According to the transmission electron microscope measurements, the layer structure improvement with barrier layers can be attributed to the suppression of the crystallization of vanadium inside the structure. Using the interface engineered multilayer, a maximum soft x-ray reflectance of 24.3% is achieved at lambda=2.441 nm, under the grazing incidence of 42 degrees . PMID- 26872168 TI - Continuous-wave, single-frequency 229 nm laser source for laser cooling of cadmium atoms. AB - Continuous-wave output at 229 nm for the application of laser cooling of Cd atoms was generated by the fourth harmonic using two successive second-harmonic generation stages. Employing a single-frequency optically pumped semiconductor laser as a fundamental source, 0.56 W of output at 229 nm was observed with a 10 mm long, Brewster-cut BBO crystal in an external cavity with 1.62 W of 458 nm input. Conversion efficiency from 458 nm to 229 nm was more than 34%. By applying a tapered amplifier (TA) as a fundamental source, we demonstrated magneto-optical trapping of all stable Cd isotopes including isotopes Cd111 and Cd113, which are applicable to optical lattice clocks. PMID- 26872169 TI - Time-resolved four-wave-mixing spectroscopy for inner-valence transitions. AB - Noncollinear four-wave-mixing (FWM) techniques at near-infrared (NIR), visible, and ultraviolet frequencies have been widely used to map vibrational and electronic couplings, typically in complex molecules. However, correlations between spatially localized inner-valence transitions among different sites of a molecule in the extreme ultraviolet (XUV) spectral range have not been observed yet. As an experimental step toward this goal, we perform time-resolved FWM spectroscopy with femtosecond NIR and attosecond XUV pulses. The first two pulses (XUV-NIR) coincide in time and act as coherent excitation fields, while the third pulse (NIR) acts as a probe. As a first application, we show how coupling dynamics between odd- and even-parity, inner-valence excited states of neon can be revealed using a two-dimensional spectral representation. Experimentally obtained results are found to be in good agreement with ab initio time-dependent R-matrix calculations providing the full description of multielectron interactions, as well as few-level model simulations. Future applications of this method also include site-specific probing of electronic processes in molecules. PMID- 26872170 TI - Flexible and fluorophore-doped luminescent solar concentrators based on polydimethylsiloxane. AB - We demonstrate a simple and inexpensive method to fabricate flexible and fluorophore-doped luminescent solar concentrators (LSCs). Polydimethylsiloxane (PDMS) serves as a host material which additionally offers the potential to cast LSCs in arbitrary shapes. The laser dye Pyrromethene 567 is used as a prototype fluorophore, and it is shown that it has a high quantum yield of 93% over the concentration range investigated. The optical efficiency and loss channels of the flexible LSCs are investigated; it is also demonstrated that the efficiency remains high while bending the LSC which is essential for flexible LSCs to make an impact on solar energy. PMID- 26872171 TI - Three-dimensional shape measurement with an arbitrarily arranged projection moire system. AB - A complete description of a three-dimensional shape measurement method with an arbitrarily arranged projection moire system is presented, including the mathematical derivation of theoretical equations, phase-to-height calibration technique, and experimental result of practical object. The proposed method requires neither a specific system setup configuration nor a manual determination of system geometric parameters, and it yields high measurement resolution and accuracy while allowing the system components to be arbitrarily positioned. A real experiment has been conducted to verify the validity of this method. PMID- 26872172 TI - Zernike x-ray ptychography. AB - We present an imaging technique combining Zernike phase-contrast imaging and ptychography. The contrast formation is explained by following the theory of Zernike phase-contrast imaging. The method is demonstrated with x-rays at a photon energy of 6.2 keV, showing how ptychographic reconstruction of a phase sample leads to a Zernike phase-contrast image appearing in the amplitude reconstruction. In addition, the results presented in this Letter indicate an improvement of the resolution of the reconstructed object in the case of Zernike ptychography compared with the conventional one. PMID- 26872173 TI - Photoacoustic elastography. AB - Elastography can noninvasively map the elasticity distribution in biological tissue, which can potentially be used to reveal disease conditions. In this Letter, we have demonstrated photoacoustic elastography by using a linear-array photoacoustic computed tomography system. The feasibility of photoacoustic elastography was first demonstrated by imaging the strains of single-layer and bilayer gelatin phantoms with various stiffness values. The measured strains agreed well with theoretical values, with an average error of less than 5.2%. Next, in vivo photoacoustic elastography was demonstrated on a mouse leg, where the fat and muscle distribution was mapped based on the elasticity contrast. We confirmed the photoacoustic elastography results by ultrasound elastography performed simultaneously. PMID- 26872174 TI - Enhancement of magneto-optical Faraday effects and extraordinary optical transmission in a tri-layer structure with rectangular annular arrays. AB - The properties of optics and magneto-optical Faraday effects in a metal dielectric tri-layer structure with subwavelength rectangular annular arrays are investigated. It is noteworthy that we obtained the strongly enhanced Faraday rotation of the desired sign along with high transmittance by optimizing the parameters of the nanostructure in the visible spectral ranges. In this system, we obtained two extraordinary optical transmission (EOT) resonant peaks with enhanced Faraday rotations, whose signs are opposite, which may provide the possibility of designing multi-channel magneto-optical devices. Study results show that the maximum of the figure of merit (FOM) of the structure can be obtained between two EOT resonant peaks accompanied by an enhanced Faraday rotation. The positions of the maximum value of the FOM and resonant peaks of transmission along with a large Faraday rotation can be tailored by simply adjusting the geometric parameters of our models. These research findings are of great importance for future applications of magneto-optical devices. PMID- 26872175 TI - Shot-to-shot diagnostic of the longitudinal photon source position at the SPring 8 Angstrom Compact Free Electron Laser by means of x-ray grating interferometry. AB - We present single-shot measurements of the longitudinal photon source position of the SPring-8 Angstrom Compact Free Electron Laser x-ray free electron laser by means of x-ray grating interferometry. The measurements were performed in order to study the behavior of the source under normal operation conditions and as a dependence on the active undulator length. The retrieved experimental results show that x-ray grating interferometry is a powerful in situ monitoring tool for investigating and tuning an x-ray free electron laser. PMID- 26872176 TI - Self-induced transparency mode locking, and area theorem. AB - Self-induced transparency mode locking (or coherent mode locking, CML), which is based on intracavity self-induced transparency soliton dynamics, potentially allows achievement of nearly single-cycle intracavity pulse durations, much below the phase relaxation time T2 in a laser which, despite having great promise, has not yet been realized experimentally. We develop a diagram technique which allows us to predict the main features of CML regimes in a generic two section laser far from the single-cycle limit. We show that CML can arise directly at the first laser threshold if the phase relaxation time is large enough. Furthermore, we discuss the stability of the corresponding mapping. We also predict the existence of "super-CML regimes," with a pulse coupled to several Rabi oscillations in the nonlinear medium. PMID- 26872177 TI - Photonic gauge potential in a system with a synthetic frequency dimension. AB - We generalize the concept of photonic gauge potential in real space by introducing an additional "synthetic" frequency dimension in addition to the real space dimensions. As an illustration, we consider a one-dimensional array of ring resonators, each supporting a set of resonant modes having a frequency comb with spacing Omega, and undergoing a refractive index modulation at the modulation frequency equal to Omega. We show that the modulation phase provides a gauge potential in the synthetic two-dimensional space with the dimensions being the frequency and the spatial axes. Such a gauge potential can create a topologically protected one-way edge state in the synthetic space that is useful for high efficiency generation of higher-order side bands. PMID- 26872178 TI - Noise analysis for through-focus scanning optical microscopy. AB - A systematic noise-analysis study for optimizing data collection and data processing parameters for through-focus scanning optical microscopy (TSOM) is presented. TSOM is a three-dimensional shape metrology method that can achieve sub-nanometer measurement sensitivity by analyzing sets of images acquired through focus using a conventional optical microscope. We show that the best balance between signal-to-noise performance and acquisition time can be achieved by judicious spatial averaging. Correct background-signal subtraction of the imaging system inhomogeneities is also critical, as well as careful alignment of the constituent images in the case of differential TSOM analysis. PMID- 26872179 TI - Dark-field imaging as a noninvasive method for characterization of whispering gallery modes in microdisk cavities. AB - Whispering gallery mode microdisk cavities fabricated by direct laser writing are studied using dark-field imaging and spectroscopy in the visible spectral range. Dark-field imaging allows us to directly visualize the spatial intensity distribution of whispering gallery modes. We extract their azimuthal and radial mode indices from dark-field images, and find the axial mode number from the dispersion relation. The scattering spectrum obtained in the confocal arrangement provides information on the density of optical states in the resonator. The proposed technique is a simple noninvasive way to characterize the optical properties of microdisk cavities. PMID- 26872181 TI - Scaled-model guidelines for formation-flying solar coronagraph missions. AB - Stray light suppression is the main concern in designing a solar coronagraph. The main contribution to the stray light for an externally occulted space-borne solar coronagraph is the light diffracted by the occulter and scattered by the optics. It is mandatory to carefully evaluate the diffraction generated by an external occulter and the impact that it has on the stray light signal on the focal plane. The scientific need for observations to cover a large portion of the heliosphere with an inner field of view as close as possible to the photospheric limb supports the ambition of launching formation-flying giant solar coronagraphs. Their dimension prevents the possibility of replicating the flight geometry in a clean laboratory environment, and the strong need for a scaled model is thus envisaged. The problem of scaling a coronagraph has already been faced for exoplanets, for a single point source on axis at infinity. We face the problem here by adopting an original approach and by introducing the scaling of the solar disk as an extended source. PMID- 26872180 TI - Slow light Mach-Zehnder interferometer as label-free biosensor with scalable sensitivity. AB - The design, fabrication, and characterization of a label-free Mach-Zehnder interferometer (MZI) optical biosensor that incorporates a highly dispersive one dimensional (1D) photonic crystal in one arm are presented. The sensitivity of this slow light MZI-based sensor scales with the length of the slow light photonic crystal region. The numerically simulated sensitivity of a MZI sensor with a 16 MUm long slow light region is 115,000 rad/RIU-cm, which is sevenfold higher than traditional MZI biosensors with millimeter-length sensing regions. An experimental bulk refractive index detection sensitivity of 84,000 rad/RIU-cm is realized and nucleic acid detection is also demonstrated. PMID- 26872182 TI - Phase matched parametric amplification via four-wave mixing in optical microfibers. AB - Four-wave mixing (FWM) based parametric amplification in optical microfibers (OMFs) is demonstrated over a wavelength range of over 1000 nm by exploiting their tailorable dispersion characteristics to achieve phase matching. Simulations indicate that for any set of wavelengths satisfying the FWM energy conservation condition there are two diameters at which phase matching in the fundamental mode can occur. Experiments with a high-power pulsed source working in conjunction with a periodically poled silica fiber (PPSF), producing both fundamental and second harmonic signals, are undertaken to investigate the possibility of FWM parametric amplification in OMFs. Large increases of idler output power at the third harmonic wavelength were recorded for diameters close to the two phase matching diameters. A total amplification of more than 25 dB from the initial signal was observed in a 6 mm long optical microfiber, after accounting for the thermal drift of the PPSF and other losses in the system. PMID- 26872183 TI - Effect of femtosecond photo-treatment on inscription of fiber Bragg gratings. AB - Pre- and post-treatment of optical fibers is typically used to improve the fiber Bragg grating (FBG) fabrication process. Here, we investigate experimentally the effects of femtosecond photo-treatment on the ability to inscribe and erase FBGs in standard, non-sensitized, silica SMF fibers. We observe "immunity" to inscription after applying a suitable pre-treatment to the fiber and full "erasure" of the FGB after applying a suitable post-treatment. We characterize the required photo-treatment parameters and compare to FBG inscription on an untreated fiber. We believe that pre/post-photo-treatment of the fibers with fs pulses may have practical advantages such as modifying standard grating structures or observing ultrafast transient effects more clearly. PMID- 26872184 TI - Achromatization of conical diffraction: application to the generation of a polychromatic optical vortex. AB - Vortex beams are plagued by the intrinsic chromaticity of the physical phenomenon used to generate them. To the authors' best knowledge, attempts to generate them in a broad spectral range remain quite scarce and limited in their results. Crystal optics and especially conical diffraction (CD) (or refraction) intrinsically create achromatic vortices. The vortex is created by a wavelength independent topological charge, embedded directly in the Fresnel equations. However, for biaxial crystals of low crystallographic symmetry, which includes all crystals used practically for CD, the dispersion of the binormal axis creates a chromaticity effect. In this Letter, we propose a new way to compensate this dispersion of the binormal axis of a biaxial crystal in order to generate white light vortex beams by CD in a 250 nm spectral range, covering almost all the visible range. The advantages of the ability to use CD in a wide spectral range vastly exceed the sole generation of vortex beams. PMID- 26872185 TI - Compact and high extinction ratio polarization beam splitter using subwavelength grating couplers. AB - A compact and high extinction ratio polarization beam splitter using subwavelength grating (SWG) couplers is proposed and characterized, where the SWG couplers are located between the two input/output strip waveguides, including SWG based transitions combined at both ends. The TM mode can be confined well in the strip waveguide and transmits along it with nearly neglected coupling, while the TE mode undergoes a strong coupling and is transferred to the adjacent waveguide with the help of SWG couplers due to dissimilar modal characteristics and cutoff conditions between these two polarizations. To further enhance the performance, an additional tapered waveguide is added in the lateral end of the input SWG based transition. Results show that a total length of 6.8 MUm with an insertion loss of 0.08 (0.36) dB, extinction ratio (ER) of 32.19 (20.93) dB, and reflection loss of -34.76 (-32.59) dB for TE (TM) mode is obtained at 1.55 MUm; its bandwidth can be enlarged to ~81 nm for an ER>18 dB. In addition, fabrication tolerances and mode-field evolution are also presented. PMID- 26872186 TI - Broadband two-stage frequency conversion of CO laser in AgGaSe(2) crystal. AB - For the first time, to the best of our knowledge, a broadband two-stage frequency conversion of multiline CO laser radiation was theoretically and experimentally demonstrated in a single AgGaSe2 crystal. The first stage is sum frequency generation of CO laser radiation. The second stage is concurrent difference frequency generation within 4.3-4.9 MUm spectral range when mixing sum frequency radiation with the pump radiation in the same AgGaSe2 crystal. Internal sum frequency generation efficiency of multiline CO laser was up to 1%, while internal difference frequency generation efficiency was up to 0.065%. PMID- 26872187 TI - Sub-diffuse optical biomarkers characterize localized microstructure and function of cortex and malignant tumor. AB - This study uses a sub-diffusive light transport model to analyze fiber-optic measurements of reflectance spectra to recover endogenous tissue biomarkers and to correct raw fluorescence emissions for distortions from background optical properties. Measurements in tissue-simulating phantoms validated accurate recovery of the reduced scattering coefficient [(0.3-3.4 mm-1), error 10%], blood volume fraction [(1-3 vol%), error 7%], and a dimensionless metric of anisotropic scattering, gamma, that is sensitive to submillimeter tissue ultrastructure [(1.29-2.06), error 11%]. In vivo sub-diffusive optical data acquired during clinical neurosurgeries characterize differences in microstructure (gamma), perfusion (blood volume), and metabolism (PpIX fluorescence) between normal cortex and malignant tumor. PMID- 26872188 TI - Photonic jets from Babinet's cuboid structures in the reflection mode. AB - In this Letter, we demonstrate applicability of Babinet's principle of complementary diffractive structures for the formation of near-field photonic jets in the reflection mode. Structures, complementary to dielectric cuboids, are characterized with additional geometric and electromagnetic parameters compared to initial cuboids and, for this reason, offer more opportunities for the design of photonic jets with required properties. Babinet's structures allow control of such parameters of photonic jets as the focus length, width, length, maximal field intensity, and ellipticity of jets. PMID- 26872189 TI - No free lunch: the trade-off between heralding rate and efficiency in microresonator-based heralded single photon sources. AB - Generation of heralded single photons has recently been demonstrated using spontaneous four-wave mixing in integrated microresonators. While the results of coincidence measurements on the generated photon pairs from these systems show promise for their utility in heralding applications, such measurements do not reveal all of the effects of photon losses within the resonator. These effects, which include a significant degradation of the heralding efficiency, depend strongly on the relative strengths of the coupling of the ring modes to loss modes and channel modes. We show that the common choice of critical coupling neither optimizes the rate of successfully heralded photons nor coincidences and derives the coupling conditions needed to do so. Optimizing these rates has a considerable negative effect on the heralding efficiency. PMID- 26872190 TI - UVC upconversion material under sunlight excitation: LiYF(4): Pr(3+). AB - UVC upconversion emission is observed in a LiYF4:Pr3+ microcrystal under sunlight excitation. The dependence of UVC UC emission intensity on the excitation density of a 488 nm laser and sunlight is investigated. The obtained data indicates that two-photon processes play an important role in UVC UC emission. The UVC UC mechanisms of Pr3+ under the excitation of a laser and sunlight are presented and discussed. The UVC emission under sunlight excitation has broad prospects for application. PMID- 26872191 TI - Dynamics of a small particle in a fluctuating random light field. AB - The dynamics of an electric dipole in a light field consisting of electromagnetic plane waves with polarizations randomly distributed and fluctuating phases is theoretically analyzed. The expression for the optical random-force fluctuations is derived and found to be proportional to the scattering cross section and to the square of the intensity divided by the frequency of the electromagnetic field. Under these fluctuations, and in the absence of damping, the dipole behaves like a super-diffusive particle with a kinetic energy growing linearly with time. The analytic predictions are tested against numerical simulations for the particular case of a resonant dipole. PMID- 26872192 TI - One-way surface magnetoplasmon cavity and its application for nonreciprocal devices. AB - We theoretically analyze surface magnetoplasmon modes in a compact circular cavity made of magneto-optical material under a static magnetic field. Such a cavity provides two different methods for the surface wave to circulate in a unidirectional manner around the cavity, which offers more freedom, both in the one-way direction and in the frequency range, for designing nonreciprocal photonic components. We also show the interaction between this one-way cavity and waveguides through the example of a circulator, which lays the fundamental groundwork for potential nonreciprocal devices. PMID- 26872193 TI - Assessment of mono-shot measurement as a fast and accurate determination of the laser-induced damage threshold in the sub-picosecond regime. AB - Standard test protocols need several laser shots to assess the laser-induced damage threshold of optics and, consequently, large areas are necessary. Taking into account the dominating intrinsic mechanisms of laser damage in the sub picosecond regime, a simple, fast, and accurate method, based on correlating the fluence distribution with the damage morphology after only one shot in optics is therein presented. Several materials and components have been tested using this method and compared to the results obtained with the classical 1/1 method. Both lead to the same threshold value with an accuracy in the same order of magnitude. Therefore, this mono-shot testing could be a straightforward protocol to evaluate damage threshold in short pulse regime. PMID- 26872194 TI - Fractal morphology of black carbon aerosol enhances absorption in the thermal infrared wavelengths. AB - In this Letter, we numerically calculate the mass absorption cross sections (MACs) of black carbon fractal aggregates in the thermal infrared solar spectrum. Compared to equivalent-size spheres, the MAC values of aggregates show a percent enhancement of ~150 and 400 at small and large length scales, respectively. The absorption properties of aggregates with size parameters >1 surprisingly continued to remain in the Rayleigh optics regime. We explain this phenomenon using the Maxwell-Garnett effective medium theory and the concept of phase shift parameter. PMID- 26872195 TI - Square-wave oscillations in a semiconductor ring laser subject to counter directional delayed mutual feedback. AB - Square-wave (SW) switching of the lasing direction in a semiconductor ring laser (SRL) is investigated using counter-directional mutual feedback. The SRL is electrically biased to a regime that supports lasing in either counter-clockwise (CCW) or clockwise (CW) direction. The CCW and CW modes are then counter directionally coupled by optical feedback, where the CCW-to-CW and CW-to-CCW feedback are delayed by tau1 and tau2, respectively. The mutual feedback invokes SW oscillations of the CCW and CW emission intensities with a period of T~tau1+tau2. When tau1=tau2, symmetric SWs with a duty cycle of 50% are obtained, where the switching time and electrical linewidth of the SWs can be reduced to, respectively, 1.4 ns and 1.1 kHz by strengthening the feedback. When tau1?tau2, asymmetric SWs are obtained with a tunable duty cycle of tau1/(tau1+tau2). High-order symmetric SWs with a period of T=(tau1+tau2)/n can also be observed for some integer n. Symmetric SWs of order n=13 with a period of T=10.3 ns are observed experimentally. PMID- 26872196 TI - Flexible terahertz modulator based on coplanar-gate graphene field-effect transistor structure. AB - The terahertz (THz) modulators, as an essential component of the THz system, have been developed by many efforts until now. However, the development of flexible THz modulators is hindered due to the lack of flexible THz modulating materials. Herein, for the first time to the best of our knowledge, we demonstrated the feasibility of flexible THz modulators based on the coplanar-gate field-effect transistor (FET) structure of ion-gel/graphene/polyethylene terephthalate. The THz transmittance through this THz graphene modulator can be well controlled with a modulation depth up to 22% by tuning the carrier concentration of graphene via electrical gating. Furthermore, because of the integration of high flexibilities of graphene, ion-gel, and polyethylene terephthalate (PET), the proposed THz graphene modulator shows superior flexible performance, where the modulation properties can be maintained almost unchanged, not only under bending deformations, but also before and after bending 1000 times. In addition, due to the unique structure of ion-gel/graphene/PET, the flexible THz graphene modulator has a low insertion loss (1.2 dB). Therefore, this Letter is expected to be beneficial for the potential applications, ranging from the traditional compact THz system to a new flexible THz technology. PMID- 26872197 TI - Silicon waveguide grating coupler for perfectly vertical fiber based on a tilted membrane structure. AB - A grating coupler for interfacing between a silicon-on-insulator waveguide and a single-mode fiber located at a perfectly vertical direction is demonstrated based on a tilted membrane structure. The proposed design is compatible with that of conventional grating couplers for oblique fibers and facilitates mass production. A peak coupling efficiency of 28.5% and 1 dB bandwidth of 38 nm are obtained experimentally for transverse-electrics polarized light. Back reflection in the SOI waveguide is also estimated to be 1.4%. The present grating coupler for perfectly vertical fiber exhibits similar performances to the conventional grating coupler for oblique fiber concerning coupling efficiency, bandwidth, and back reflections. PMID- 26872198 TI - Annular arrayed-waveguide fiber for autofocusing Airy-like beams. AB - We propose and theoretically demonstrate a novel optical fiber with an annular arrayed-waveguide to implement Airy phase and amplitude modulation, and generate an abruptly autofocusing circular Airy beam. The properties of wave propagation in Airy fiber and free space are studied by using the coupled-mode theory and angular spectrum method. The calculated results show that the output beam from such a fiber has a circular Airy-like pattern and can autofocus with the intensity maxima following a parabolic trajectory. We also show that the position of the focus point of the output beam from the Airy fiber can be easily controlled by changing input wavelength. PMID- 26872199 TI - Surface leakage current in 12.5 MUm long-wavelength HgCdTe infrared photodiode arrays. AB - Long-wavelength (especially >12 MUm) focal plane array (FPA) infrared detection is the cutting edge technique for third-generation infrared remote sensing. However, dark currents, which are very sensitive to the growth of small Cd composition HgCdTe, strongly limits the performance of long wavelength HgCdTe photodiode arrays in FPAs. In this Letter, 12.5 MUm long-wavelength Hg1 xCdxTe (x~0.219) infrared photodiode arrays are reported. The variable-area and variable-temperature electrical characteristics of the long wavelength infrared photodiodes are measured. The characteristics of the extracted zero-bias resistance-area product (l/R0A) varying with the perimeter-to-area (P/A) ratio clearly show that surface leakage current mechanisms severely limit the overall device performance. A sophisticated model has been developed for investigating the leakage current mechanism in the photodiodes. Modeling of temperature-dependent I-V characteristic indicates that the trap-assisted tunneling effect dominates the dark current at 50 K resulting in nonuniformities in the arrays. The extracted trap density, approximately 1013-1014 cm-3, with an ionized energy of 30 meV is determined by simulation. The work described in this Letter provides the basic mechanisms for a better understanding of the leakage current mechanism for long-wavelength (>12 MUm) HgCdTe infrared photodiode arrays. PMID- 26872200 TI - Ultrasensitive vector bending sensor based on multicore optical fiber. AB - In this Letter, we demonstrate a compellingly simple directional bending sensor based on multicore optical fibers (MCF). The device operates in reflection mode and consists of a short segment of a three-core MCF that is fusion spliced at the distal end of a standard single mode optical fiber. The asymmetry of our MCF along with the high sensitivity of the supermodes of the MCF make the small bending on the MCF induce drastic changes in the supermodes, their excitation, and, consequently, on the reflected spectrum. Our MCF bending sensor was found to be highly sensitive (4094 pm/deg) to small bending angles. Moreover, it is capable of distinguishing multiple bending orientations. PMID- 26872201 TI - Low-loss and broadband 2 * 2 silicon thermo-optic Mach-Zehnder switch with bent directional couplers. AB - A low-loss and broadband silicon thermo-optic switch is proposed and demonstrated experimentally by using a Mach-Zehnder Interferometer with 2*2 3 dB power splitters based on bent directional couplers (DCs). The bent DCs are introduced here to replace the traditional 2*2 3 dB power splitters based on multimode interferometers or straight DCs, so that one achieves a coupling ratio of ~50%? 50%, as well as low excess loss over a broadband. The demonstrated Mach-Zehnder switch (MZS) has a ~140 nm bandwidth for an excess loss of <1 dB and an extinction ratio of >20 dB. The present MZS also shows excellent reproducibility and good fabrication tolerance, which makes it promising for realizing N*N optical switches. PMID- 26872202 TI - Deep turbulence effects mitigation with coherent combining of 21 laser beams over 7 km. AB - We demonstrate coherent beam combining and adaptive mitigation of atmospheric turbulence effects over 7 km under strong scintillation conditions using a coherent fiber array laser transmitter operating in a target-in-the-loop setting. The transmitter system is composed of a densely packed array of 21 fiber collimators with integrated capabilities for piston, tip, and tilt control of the outgoing beams wavefront phases. A small cat's-eye retro reflector was used for evaluation of beam combining and turbulence compensation performance at the target plane, and to provide the feedback signal for control of piston and tip/tilt phases of the transmitted beams using the stochastic parallel gradient descent maximization of the power-in-the-bucket metric. PMID- 26872203 TI - Self-mixing interferometry with mutual independent orthogonal polarized light. AB - A self-mixing interferometry with mutual independent orthogonal polarized light is introduced. Its most important feature is that two mutual independent orthogonal lights are used as measuring and reference light. Frequency shifting and polarization multiplexing technologies are used in the proposed optical system. Phase variation of the two orthogonal polarized beams is simultaneously measured through heterodyne demodulation with a lock-in amplifier. The phase difference of the orthogonal polarized light accurately reflects the target displacement. The target in this system is a non-cooperative object which is different from a traditional Michelson interferometer. The primary experimental results show that this kind of self-mixing interferometry is very feasible. Under typical room conditions, the system's short-term resolution is better than 2 nm. PMID- 26872204 TI - Hybrid Pyrrole-Imidazole Alkaloids from the Sponge Agelas sceptrum. AB - A chemical investigation of the tropical sponge Agelas sceptrum from Plana Cays (Bahamas) led to the isolation of two hybrid pyrrole-imidazole alkaloids (PIAs), 15'-oxoadenosceptrin (1) and decarboxyagelamadin C (2). Herein, we report their challenging structure elucidation established by NMR and ECD spectroscopy. 15' Oxoadenosceptrin (1) shows sceptrin merged with an adenine moiety, not yet encountered in the PIA family, whereas decarboxyagelamadin C (2) is a close derivative of agelamadins C to E recently isolated from an Agelas sp. from Okinawa. PMID- 26872205 TI - Fracture risk in patients with haemophilia. PMID- 26872206 TI - Dermatan 4-O-sulfotransferase 1-deficient Ehlers-Danlos syndrome complicated by a large subcutaneous hematoma on the back. PMID- 26872207 TI - Ionic Liquid Dynamics Measured with 2D IR and IR Pump-Probe Experiments on a Linear Anion and the Influence of Potassium Cations. AB - The room-temperature ionic liquid EmimNTf2 (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) was studied with two-dimensional infrared (2D IR) spectroscopy and polarization selective pump-probe (PSPP) experiments using low-concentration selenocyanate (SeCN(-)) as the vibrational probe. SeCN(-) was added as EmimSeCN, which keeps the cation the same. KSeCN was also used, so K(+) was added. Two 2D IR polarization configurations were employed: ?XXXX? (all pulses have the same polarization) and ?XXYY? (the first two pulse polarizations are perpendicular to that of the third pulse and the echo). The spectral diffusion differs for the two configurations, demonstrating that reorientation induced spectral diffusion, in addition to structural spectral diffusion (SSD), plays a role in the observed dynamics. The SSD was extracted from the 2D IR time dependent data. The samples with EmimSeCN have dynamics on several fast time scales; however, when KSeCN is used, both the PPSP anisotropy decay and the 2D IR decays have low amplitude offsets (nondecaying values at long times). The size of the offsets increased with increased K(+) concentration. These results are explained in terms of a two-ensemble model. A small fraction of the SeCN(-) is located in the regions modified by the presence of K(+), causing a substantial slowing of the SeCN(-) orientational relaxation and spectral diffusion. Having a small ensemble of SeCN(-) that undergoes very slow dynamics is sufficient to explain the offsets. For the major ensemble, the dynamics with and without K(+) are the same. PMID- 26872209 TI - Genetics of congenital heart disease. AB - PURPOSE OF REVIEW: The goal of this review is to highlight recent discoveries in the field of genetics as it relates to congenital heart disease (CHD). Recent advancements in next generation sequencing technology and tools to interpret this growing body of data have allowed us to refine our understanding of the molecular mechanisms that result in CHD. RECENT FINDINGS: From multiple different study designs, the genetic lesions that cause CHD are increasingly being elucidated. Of the more novel findings, a forward genetic screen in mice has implicated recessive inheritance and the ciliome broadly in CHD pathogenesis. The developmental delays frequently observed in patients with CHD appear to result from mutations affecting genes that overlap heart and brain developmental regulation. A meta-analysis has provided clarity, discriminating pathologic from incidental copy number variations and defining a critical region or gene. SUMMARY: Recent technological advances have rapidly expanded our understanding of CHD genetics, and support the applicability to the clinical domain in both sporadic and inherited disease. Though significant gaps remain, genetic lesions remain the primary explanation for CHD pathogenesis, although the precise mechanism is likely multifactorial. PMID- 26872208 TI - Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. AB - Rapamycin, an inhibitor of mTOR signaling, has been shown to reverse diastolic dysfunction in old mice in 10 weeks, highlighting its therapeutic potential for a poorly treatable condition. However, the mechanisms and temporal regulation of its cardiac benefits remain unclear. We show that improved diastolic function in old mice begins at 2-4 weeks, progressing over the course of 10-week treatment. While TORC1-mediated S6 phosphorylation and TORC2 mediated AKT and PKCalpha phosphorylation are inhibited throughout the course of treatment, rapamycin inhibits ULK phosphorylation and induces autophagy during just the first week of treatment, returning to baseline at two weeks and after. Concordantly, markers of mitochondrial biogenesis increase over the first two weeks of treatment and return to control levels thereafter. This transient induction of autophagy and mitochondrial biogenesis suggests that damaged mitochondria are replaced by newly synthesized ones to rejuvenate mitochondrial homeostasis. This remodeling is shown to rapidly reverse the age-related reduction in fatty acid oxidation to restore a more youthful substrate utilization and energetic profile in old isolated perfused hearts, and modulates the myocardial metabolomein vivo. This study demonstrates the differential and dynamic mechanisms following rapamycin treatment and highlights the importance of understanding the temporal regulation of rapamycin effects. PMID- 26872210 TI - Effects of the Financial Crisis on Psychotropic Drug Consumption in a Cohort from a Semi-Urban Region in Catalonia, Spain. AB - PURPOSE: Evidence of whether the recent economic crisis has or has not had an effect on psychotropic drug consumption is very scarce. Our objective was to determine if there had in fact been an increase in psychotropic drug use as a result of the financial crisis. METHODS: In our study a retrospective cohort (between January 1, 2005, and December 31, 2012) was made up of individuals from the general population in a region in the northeast of Catalonia, Spain. We specified a generalized linear mixed model along with combined 'selection on observables' as (propensity scoring) matching and 'selection on unobservables' as (random coefficient) the panel data model methods, and performed inferences using a Bayesian framework. RESULTS: In the period following the economic crisis (post 2009), there was an increase in the consumption of psychotropic drugs which was significantly higher among those who had already been consuming psychotropic drugs prior to 2009 and those most likely to be unemployed. The increase was of greater significance when consumption was measured by the number of drugs being taken, rather than by the defined daily dose (DDD), with the greatest increase occurring in 2011; the very year in which Spain was most affected by the crisis. CONCLUSIONS: Once the financial crisis had ended, there was an increase in the severity, rather than the intensity, of mental health disorders in individuals who had already had disorders before the crisis. This increase occurred in those most likely to be unemployed, and the severity was accentuated in the toughest year of the economic crisis. PMID- 26872211 TI - Peroxiredoxin 5 Protects TGF-beta Induced Fibrosis by Inhibiting Stat3 Activation in Rat Kidney Interstitial Fibroblast Cells. AB - Renal fibrosis is a common final pathway of end-stage kidney disease which is induced by aberrant accumulation of myofibroblasts. This process is triggered by reactive oxygen species (ROS) and proinflammatory cytokines generated by various source of injured kidney cells. Peroxiredoxin 5 (Prdx5) is a thiol-dependent peroxidase that reduces oxidative stress by catalyzing intramolecular disulfide bonds. Along with its antioxidant effects, expression level of Prdx5 also was involved in inflammatory regulation by immune stimuli. However, the physiological effects and the underlying mechanisms of Prdx5 in renal fibrosis have not been fully characterized. Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO) for 1 or 7 days. For the in vitro model, NRK49F cells, a rat kidney interstitial fibroblast cell lines, were treated with transforming growth factor beta (TGF-beta) for 0, 1, 3, or 5 days. To access the involvement of its peroxidase activity in TGF-beta induced renal fibrosis, wild type Prdx5 (WT) and double mutant Prdx5 (DM), converted two active site cysteines at Cys 48 and Cys 152 residue to serine, were transiently expressed in NRK49F cells. The protein expression of Prdx5 was reduced in UUO kidneys. Upregulation of fibrotic markers, such as fibronectin and alpha-smooth muscle actin (alpha-SMA), declined at 5 days in time point of higher Prdx5 expression in TGF-beta treated NRK49F cells. The overexpression of wild type Prdx5 by transient transfection in NRK49F cells attenuated the TGF-beta induced upregulation of fibronectin and alpha-SMA. On the other hand, the transient transfection of double mutant Prdx5 did not prevent the activation of fibrotic markers. Overexpression of Prdx5 also suppressed the TGF beta induced upregulation of Stat3 phosphorylation, while phosphorylation of Smad 2/3 was unchanged. In conclusion, Prdx5 protects TGF-beta induced fibrosis in NRK49F cells by modulating Stat3 activation in a peroxidase activity dependent manner. PMID- 26872213 TI - Highly sensitive electrochemical biosensor based on nonlinear hybridization chain reaction for DNA detection. AB - In the present work we demonstrated an ultrasensitive detection platform for specific DNA based on nonlinear hybridization chain reaction (HCR) by triggering chain-branching growth of DNA dendrimers. HCR was initiated by target DNA (tDNA) and finally formed dendritic structure by self-assembly. The electrochemical signal was drastically enhanced by capturing multiple catalytic peroxidase with high-ordered growth. Electrochemical signals were obtained by measuring the reduction current of oxidized 3, 3', 5, 5'-tetramethylbenzidine sulfate (TMB), which was generated by HRP in the presence of H2O2. This method exhibited ultrahigh sensitivity to tDNA with detection limit of 0.4 fM. Furthermore, the biosensor was also capable of discriminating single-nucleotide difference among concomitant DNA sequences. PMID- 26872212 TI - Increased Frequency of T Follicular Helper Cells and Elevated Interleukin-27 Plasma Levels in Patients with Pemphigus. AB - Pemphigus is an autoimmune disease in which IgG auto-antibodies (auto-ab) against the desmosomal cadherins desmoglein (Dsg) 3 and Dsg1 cause loss of epidermal keratinocyte adhesion. Aim of this study was to investigate cytokines derived from antigen-presenting cells (APC) and their relation to CD4+ T cell subpopulations and to the auto-ab response in pemphigus. In this regard, patients with pemphigus were compared to patients with myasthenia gravis (MG), an unrelated auto-ab-mediated autoimmune disease, and healthy controls. In pemphigus and MG, the plasma concentrations of the APC-derived immunomodulatory cytokine IL 27 were highly increased. Strikingly, IL-27 strongly correlated with Dsg-specific IgG auto-ab titers. T helper (Th) 17 cells were augmented in both pemphigus and MG patients while T follicular helper (Tfh) cells, which are essential in providing B cell help, were increased only in pemphigus along with increasing plasma concentrations of IL-21, a cytokine produced by Th17 and Tfh cells. Moreover, we could detect Dsg3-specific autoreactive T cells producing IL-21 upon ex vivo stimulation with Dsg3. These findings suggest that IL-27 and IL-21 producing T cells, are involved in the pathogenesis of pemphigus. The further characterization of IL-21-producing T cells and of the role of IL-27 will lead to a more defined understanding of the auto-ab response in pemphigus. PMID- 26872215 TI - The synthesis and self-assembly of disc-cube dyads with spacers of different lengths. AB - Disc-cube dyads with a polyhedral oligomeric silsesquioxane (POSS) molecule covalently attached to a hexa-peri-hexabenzocoronene (HBC) molecule were designed and synthesized. The results demonstrate that the length of a spacer plays an important role in the self-assembly behavior of the HBC-POSS dyad. PMID- 26872214 TI - Concentration Sensing by the Moving Nucleus in Cell Fate Determination: A Computational Analysis. AB - During development of the vertebrate neuroepithelium, the nucleus in neural progenitor cells (NPCs) moves from the apex toward the base and returns to the apex (called interkinetic nuclear migration) at which point the cell divides. The fate of the resulting daughter cells is thought to depend on the sampling by the moving nucleus of a spatial concentration profile of the cytoplasmic Notch intracellular domain (NICD). However, the nucleus executes complex stochastic motions including random waiting and back and forth motions, which can expose the nucleus to randomly varying levels of cytoplasmic NICD. How nuclear position can determine daughter cell fate despite the stochastic nature of nuclear migration is not clear. Here we derived a mathematical model for reaction, diffusion, and nuclear accumulation of NICD in NPCs during interkinetic nuclear migration (INM). Using experimentally measured trajectory-dependent probabilities of nuclear turning, nuclear waiting times and average nuclear speeds in NPCs in the developing zebrafish retina, we performed stochastic simulations to compute the nuclear trajectory-dependent probabilities of NPC differentiation. Comparison with experimentally measured nuclear NICD concentrations and trajectory-dependent probabilities of differentiation allowed estimation of the NICD cytoplasmic gradient. Spatially polarized production of NICD, rapid NICD cytoplasmic consumption and the time-averaging effect of nuclear import/export kinetics are sufficient to explain the experimentally observed differentiation probabilities. Our computational studies lend quantitative support to the feasibility of the nuclear concentration-sensing mechanism for NPC fate determination in zebrafish retina. PMID- 26872217 TI - One-Pot Conversion of N-Allyl-alpha-cyano Esters to alpha-Allyl-alpha-cyano Lactams through a Hydrolysis/Ketene Formation/Cyclization/Claisen Rearrangement Sequence. AB - An intramolecular ketene aza-Claisen rearrangement is developed for the first time to enable the stereoselective synthesis of alpha-ally-alpha-cyano-lactams from N-allyl amino esters. This reaction also exhibits outstanding chemoselectivity when an unsymmetrical bis-N-allyl group is present in the starting molecule. The usefulness of this method is demonstrated by a short synthesis of optically active bicyclolactam from l-proline. PMID- 26872218 TI - 2alpha-Hydroxyursolic Acid Inhibited Cell Proliferation and Induced Apoptosis in MDA-MB-231 Human Breast Cancer Cells through the p38/MAPK Signal Transduction Pathway. AB - The mechanisms of action of 2alpha-hydroxyursolic acid in inhibiting cell proliferation and inducing apoptosis in MDA-MB-231 human breast cancer cells were investigated. The antiproliferative activity and cytotoxicity were determined by the methylene blue assay. The expression of proteins was determined using Western blot. 2alpha-Hydroxyursolic acid significantly inhibited MDA-MB-231 cell proliferation, and no cytotoxicity was observed at concentrations below 30 MUM. 2alpha-Hydroxyursolic acid significantly down-regulated expressions of TRAF2, PCNA, cyclin D1, and CDK4 and up-regulated the expressions of p-ASK1, p-p38, p p53, and p-21. 2alpha-Hydroxyursolic acid induced apoptosis in MDA-MB-231 cells by significantly increasing the Bax/Bcl-2 ratio and inducing the cleaved caspase 3. Additionally, treatment of SB203580, a p38 MAPK specific inhibitor, reversed the inhibition of PCNA, cyclin D1, and Bcl-2 expression induced by 2alpha hydroxyursolic acid in MDA-MB-231 cells. These results suggested that 2alpha hydroxyursolic acid exhibited anticancer activity through the inhibition of cell proliferation and the induction of apoptosis by regulating the p38/MAPK signal transduction pathway. PMID- 26872216 TI - The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java. AB - BACKGROUND: Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006 2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. CONCLUSIONS/SIGNIFICANCE: Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The circulation of all four serotypes of dengue virus was observed in most years of the study. PMID- 26872219 TI - Women's Acceptability of Misoprostol Treatment for Incomplete Abortion by Midwives and Physicians - Secondary Outcome Analysis from a Randomized Controlled Equivalence Trial at District Level in Uganda. AB - OBJECTIVE: This study aimed to assess women's acceptability of diagnosis and treatment of incomplete abortion with misoprostol by midwives, compared with physicians. METHODS: This was an analysis of secondary outcomes from a multi centre randomized controlled equivalence trial at district level in Uganda. Women with first trimester incomplete abortion were randomly allocated to clinical assessment and treatment with misoprostol by a physician or a midwife. The randomisation (1:1) was done in blocks of 12 and stratified for health care facility. Acceptability was measured in expectations and satisfaction at a follow up visit 14-28 days following treatment. Analysis of women's overall acceptability was done using a generalized linear mixed-effects model with an equivalence range of -4% to 4%. The study was not masked. The trial is registered at ClinicalTrials.org, NCT 01844024. RESULTS: From April 2013 to June 2014, 1108 women were assessed for eligibility of which 1010 were randomized (506 to midwife and 504 to physician). 953 women were successfully followed up and included in the acceptability analysis. 95% (904) of the participants found the treatment satisfactory and overall acceptability was found to be equivalent between the two study groups. Treatment failure, not feeling calm and safe following treatment, experiencing severe abdominal pain or heavy bleeding following treatment, were significantly associated with non-satisfaction. No serious adverse events were recorded. CONCLUSIONS: Treatment of incomplete abortion with misoprostol by midwives and physician was highly, and equally, acceptable to women. TRIAL REGISTRATION: ClinicalTrials.gov NCT01844024. PMID- 26872220 TI - Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children. AB - BACKGROUND: Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population. METHODS: Forty-six children with focal epilepsy and 20 controls (6-18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions"), for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions"). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject. FINDINGS: Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance. CONCLUSIONS: A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results. PMID- 26872224 TI - [Trends and reforms in long-term care policies for the elderly]. AB - One of the main public health concerns in medium and high-income countries is how to deal with problems of functional dependency of a growing number of elderly individuals. This study aimed to identify converging issues in 30 countries with formal long-term care systems. A systematic review included articles, studies, and comparative international reports published from 2010 to 2015. The results show three trends in the design and development of these policies: (a) focus on the oldest or most dependent elderly, (b) expansion of financing based on individual contribution, and (c) promotion of home care and financial benefits for care in specialized centers (nursing homes and similar establishments). All three have positive effects on cost containment, despite limited evidence of impacts on people's health. PMID- 26872225 TI - [Focus groups with women from quilombo communities in Brazil]. AB - This article discusses an experience using the focus group technique with women from a quilombo, or community of descendants of African slaves in Brazil. This is a descriptive qualitative anthropological study of 13 women from a quilombo in rural Rio Grande do Sul State, Brazil. The focus group technique allowed an approach, interaction, and exchange of knowledge, experiences, perceptions, and feelings, in addition to problematization and in-depth discussion concerning the meaning of women's health care in the quilombo. The focus group was a prime space for learning and understanding the life experiences of quilombola women and the meanings they assigned to the experiences. In order to use the focus group technique, researchers must display creativity, sensitivity, attention, respect, nonjudgmental attitudes, flexibility, prior preparation, and knowledge of the technique and specific study topic. PMID- 26872226 TI - Consumption of sugar-rich food products among Brazilian students:National School Health Survey (PeNSE 2012). AB - This study aimed to analyze the consumption of high-sugar foods by Brazilian schoolchildren and to identify associated factors, based on data from the National School Health Survey (PeNSE 2012). Consumption of these foods was classified as: do not consume sweets and soft drinks regularly; consume sweets or soft drinks regularly; and consume sweets and soft drinks regularly. Its association with sociodemographic information, eating habits, and family contexts were investigated via multiple ordinal regressions. Regular consumption of sweets and/or soft drinks was reported by 19.2% and 36.1% of adolescents, respectively, and higher prevalence was associated with female gender, age 14-15 years, higher maternal education, not living with the mother and father, not eating meals with the parents, eating while watching TV, and longer TV time. Nearly one-fifth of adolescents regularly consumed sweets and soft drinks, which was associated with socio-demographic and behavioral factors that should be targeted in order to improve their food consumption. PMID- 26872221 TI - Acylated but not des-acyl ghrelin is neuroprotective in an MPTP mouse model of Parkinson's disease. AB - The gut hormone ghrelin is widely beneficial in many disease states. However, ghrelin exists in two distinctive isoforms, each with its own metabolic profile. In Parkinson's Disease (PD) acylated ghrelin administration is neuroprotective, however, the role of des-acylated ghrelin remains unknown. In this study, we wanted to identify the relative contribution each isoform plays using the MPTP model of PD. Chronic administration of acylated ghrelin in mice lacking both isoforms of ghrelin (Ghrelin KO) attenuated the MPTP-induced loss on tyrosine hydroxylase (TH) neuronal number and volume and TH protein expression in the nigrostriatal pathway. Moreover, acylated ghrelin reduced the increase in glial fibrillary acidic protein and Ionized calcium binding adaptor molecule 1 microglia in the substantia nigra. However, injection of acylated ghrelin also elevated plasma des-acylated ghrelin, indicating in vivo deacetylation. Next, we chronically administered des-acylated ghrelin to Ghrelin KO mice and observed no neuroprotective effects in terms of TH cell number, TH protein expression, glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 cell number. The lack of a protective effect was mirrored in ghrelin-O-acyltransferase KO mice, which lack the ability to acylate ghrelin and consequently these mice have chronically increased plasma des-acyl ghrelin. Plasma corticosterone was elevated in ghrelin-O-acyltransferase KO mice and with des-acylated ghrelin administration. Overall, our studies suggest that acylated ghrelin is the isoform responsible for in vivo neuroprotection and that pharmacological approaches preventing plasma conversion from acyl ghrelin to des-acyl ghrelin may have clinical efficacy to help slow or prevent the debilitating effects of PD. Ghrelin exists in the plasma as acyl and des-acyl ghrelin. We determined the form responsible for in vivo neuroprotection in a mouse model of Parkinson's disease. Although exogenous acyl ghrelin is deacylated in situ to des-acyl, only acyl ghrelin was neuroprotective by attenuating dopamine cell loss and glial activation. Acyl ghrelin is a therapeutic option to reduce Parkinson's Disease progression. Cover Image for this issue: doi: 10.1111/jnc.13316. PMID- 26872227 TI - Factors associated with treatment for latent tuberculosis in persons living with HIV/AIDS. AB - The aim was to identify factors associated with non-initiation of prophylactic treatment of latent tuberculosis infection (LTBi) in persons living with HIV/AIDS (PLWA), based on a prospective cohort study of PLWA >= 18 years of age in two referral services for HIV/AIDS. Of the 232 patients eligible for treatment of LTBi, 69.8% initiated treatment. Following multivariate logistic regression analysis, only treatment in one of the two referral services was associated with non-initiation of treatment for LTBi (p < 0.001). TB incidence in the cohort was 0.6/100 person-years. TB incidence in patients that initiated treatment of LTBi was 0.4/100 person-years, compared to 1.2/100 person-years in those that did not initiate treatment, but the difference was not statistically significant. The study's most interesting finding was that the main factor associated with the likelihood of treatment for LTBi was the health service where the patient was treated. PMID- 26872228 TI - Parenting styles as a tobacco-use protective factor among Brazilian adolescents. AB - The objective was to evaluate the relationship between tobacco use (previous month and frequent use), parenting styles and parental smoking behavior in a sample of high school students. Participants were recruited from public and private high schools from 27 Brazilian state capitals (N = 17,246). The overall prevalence of tobacco use in life was 25.2%; 15.3% in the previous year; 8.6% in the previous month; and 3.2% for frequent use. Tobacco use by the parents was reported by 28.6% of the students. Regarding parenting styles, 39.2% were classified as negligent, 33.3% authoritative, 15.6% as indulgent and 11.9% authoritarian. Compared to adolescents with authoritative parents, those with negligent or indulgent parents were more prone to report tobacco use during the last month or frequent use. This study showed an association between parenting styles and tobacco use by high school students. Authoritative parents were associated with protection from frequent and previous month tobacco use among adolescents. PMID- 26872229 TI - Postpartum posttraumatic stress disorder in a fetal high-risk maternity hospital in the city of Rio de Janeiro, Brazil. AB - The objectives of this study were to estimate the prevalence of postpartum posttraumatic stress disorder (PTSD) in a maternity hospital for fetal high-risk pregnancies and to identify vulnerable subgroups. This was a cross-sectional study at a fetal high-risk maternity hospital in Rio de Janeiro, Brazil, with a sample of 456 women who had given birth at this hospital. The Trauma History Questionnaire and Post-Traumatic Stress Disorder Checklist were used to screen for lifetime traumatic events and PTSD symptoms, respectively. Overall prevalence of PTSD was 9.4%. Higher PTSD prevalence was associated with three or more births, a newborn with a 1-minute Apgar score of seven or less, history of mental disorder prior to or during the index pregnancy, postpartum depression, physical or psychological intimate partner violence during the pregnancy, a history of unwanted sexual experience, and lifetime exposure to five or more traumas. Rapid diagnosis and treatment of PTSD are essential to improve the mother's quality of life and the infant's health. PMID- 26872230 TI - Familial aggregation and dietary patterns in the Brazilian population. AB - The aim of the study was to identify dietary patterns in Brazil and verify aggregation among members of the same family based on the Brazilian National Dietary Survey, a nationwide dietary survey conducted in 2008-2009 in individuals over 10 years of age. Dietary intake was estimated with a food record. Dietary patterns were identified by factor analysis, and familial aggregation was verified by linear regression. Three major dietary patterns were identified: (1) a traditional snack featuring coffee, rolls, oils and fats, and cheese; (2) traditional main meal, based on rice, beans and other legumes, and meat; and (3) fast food type snacks, namely sandwiches, processed meats, soft drinks, snacks, and pizza. Pattern 2 showed the strongest association (beta = 0.37-0.64). Patterns 1 and 3 showed positive associations for all pairs of family members, with beta ranging from 0.27 to 0.44 and 0.32 to 0.42, respectively. The study showed familial aggregation of dietary patterns in the Brazilian population. PMID- 26872231 TI - [Back pain in adults: a population-based study in Campinas, Sao Paulo State, Brazil]. AB - This study aimed to estimate the prevalence of back pain in the urban population of Campinas, Sao Paulo State, Brazil, and identify the most affected groups. Data were obtained from a population survey in 2008-2009 that included 1,118 individuals aged 18-59 years. Overall prevalence of back pain was 30.6% (34.4% in women and 26.5% in men). After adjustment, prevalence was higher among women, those with less schooling, people working more than 40 hours a week, smokers and former smokers, those with no leisure-time physical activity, and those who were physically active in household chores and at work. Prevalence increased with age and with the number of children, number of diseases and health problems, and those with worse self-rated health. The results confirm the high prevalence of low back pain and the associated incapacity, indicating the population groups that require heightened attention from health services. PMID- 26872232 TI - [Intermedicality and protagonism: the role of indigenous health agents on the Kwata-Laranjal Indian Reservation in Amazonas State, Brazil]. AB - This article summarizes the results of an ethnographic study on the role of indigenous health agents on the Kwata-Laranjal Indian Reservation in Borba, Amazonas State, Brazil. The study aims to contribute to understanding the role of indigenous health agents in the expansion of the hegemonic medical model in a context of medical pluralism. The analysis included data from participant observation and interviews conducted from 2009 to 2011. Semi-structured interviews were held to record narratives on their work routine, experiences, and difficulties. The authors conclude that work by indigenous health agents is essential to primary care, and that their role extends beyond technical activities. The Munduruku indigenous health agents hold a key position in the links between indigenous and biomedical knowledge in contexts of intermedicality, emerging as new political actors in interethnic contexts. PMID- 26872233 TI - Factors associated with recidivism among adolescents girls in conflict with the law in an institution in Brasilia, Federal District, Brazil. AB - Recidivism is a challenge for the Brazilian socio-educational system because it is associated with personal, social and environmental factors, especially among juvenile offenders. This study examined key characteristics and potential association with recidivism in 391 female adolescent offenders from a correctional institution in Brasilia, Federal District, Brazil, between 2004 and 2011. Cross-sectional data on socio-demographics, drug use and offense characteristics from institutional information were examined. Associate factors with recidivism were examined using negative binomial regression analyses. 32.5% of offenders were recidivists at present admission and the mean frequency of recidivism among recidivists was 2.16. About half (53.6%) of the sample reported drug use. After the adjustment, recidivism was positively associated with: age; offender's drug use; residence status; offense type; and no family drug use. Factors associated with juvenile offenders' recidivism confirm findings from elsewhere, and should inform targeted interventions in Brazil. PMID- 26872234 TI - Physician-patient argumentation and communication, comparing Toulmin's model, pragma-dialectics, and American sociolinguistics. AB - This article discusses the application of theories of argumentation and communication to the field of medicine. Based on a literature review, the authors compare Toulmin's model, pragma-dialectics, and the work of Todd and Fisher, derived from American sociolinguistics. These approaches were selected because they belong to the pragmatic field of language. The main results were: pragma dialectics characterizes medical reasoning more comprehensively, highlighting specific elements of the three disciplines of argumentation: dialectics, rhetoric, and logic; Toulmin's model helps substantiate the declaration of diagnostic and therapeutic hypotheses, and as part of an interpretive medicine, approximates the pragma-dialectical approach by including dialectical elements in the process of formulating arguments; Fisher and Todd's approach allows characterizing, from a pragmatic analysis of speech acts, the degree of symmetry/asymmetry in the doctor-patient relationship, while arguing the possibility of negotiating treatment alternatives. PMID- 26872235 TI - [Association between coverage by oral health teams in the family health and the increase in dental care output in Brazilian municipalities, 1999 and 2011]. AB - The aim of this study was to analyze the association between population coverage by oral health teams under the Family Health Strategy (FHS) and the difference in 1999 and 2011 in rates of use of public dental services in Brazilian municipalities. The sample included all 5,507 municipalities in both years. Data were used from government information systems to perform logistic regression for modeling the increase in procedure rates. By 2011, 85% of Brazil's municipalities had oral health teams under the FHS and there had been an increase in infrastructure, human and financial resources. Dental care output increased 49.5% from 1999 to 2011. Municipalities that incorporated more than 3 oral health teams per 10,000 inhabitants showed higher odds of increasing their rates of community procedures (OR = 1.61, 95%CI: 1.23-2.11), prophylactic procedures (OR = 2.05, CI95%: 1.56-2.69), restorations (OR = 2.07, 95%CI: 1.58-2.71), and extractions (OR = 1.53, 95%CI: 1.19-1.97) after adjusting for socio-demographic factors and variations in physical, human and financial resources. The incorporation of oral health teams into the FHS appears more effective for increasing indicators of the use of dental services. PMID- 26872236 TI - [Non-adherence to biological therapy in patients with rheumatic diseases in the Brazilian Unified National Health System in Minas Gerais State, Brazil]. AB - This study examined non-adherence to biological therapy with adalimumab and etanercept and associated factors in patients with rheumatic diseases treated under the Brazilian Unified National Health System in Minas Gerais State, Brazil. A non-concurrent cohort study was performed from pharmacy records of adult patients that had recently initiated treatment. Patient non-adherence was measured by proportion of days covered (PDC), and non-adherent patients were defined as PDC < 0.8. A total of 1,150 patients were included, with the following breakdown: 64.3% rheumatoid arthritis, 8.5% psoriatic arthritis , and 27.2% ankylosing spondylitis. In total, 33.5% of patients were non-adherent. Factors such as younger age (19-39 years), female gender, diagnosis of rheumatoid arthritis , and initial treatment with etanercept were associated with low adherence. The results indicate a high prevalence of non-adherence, which can lead to worse health outcomes and increase healthcare use and costs. PMID- 26872237 TI - Prescribing errors in a Brazilian neonatal intensive care unit. AB - Pediatric patients, especially those admitted to the neonatal intensive care unit (ICU), are highly vulnerable to medication errors. This study aimed to measure the prescription error rate in a university hospital neonatal ICU and to identify susceptible patients, types of errors, and the medicines involved. The variables related to medicines prescribed were compared to the Neofax prescription protocol. The study enrolled 150 newborns and analyzed 489 prescription order forms, with 1,491 medication items, corresponding to 46 drugs. Prescription error rate was 43.5%. Errors were found in dosage, intervals, diluents, and infusion time, distributed across 7 therapeutic classes. Errors were more frequent in preterm newborns. Diluent and dosing were the most frequent sources of errors. The therapeutic classes most involved in errors were antimicrobial agents and drugs that act on the nervous and cardiovascular systems. PMID- 26872238 TI - [When and where motorcyclists have accidents and die in Belo Horizonte, Minas Gerais State, Brazil]. AB - The objective of this study was to analyze traffic accidents involving motorcycles in Belo Horizonte, Minas Gerais State, Brazil, from 2007 to 2011 and to identify clusters of high-risk and hazardous intersections in and around the city. Data were provided by the Military Police Brigade and the Emergency Medical Service (SAMU). Accident severity rates were used to identify critical intersections. Two techniques were used: kernel analysis and scan statistics (continuous Poisson model). High-risk clusters were located in the downtown area and on major thoroughfares. Surprisingly, the highest risk of accidents and death occurred not at intersections, but between them. Hazardous intersections are part of routes used to access regions around Greater Metropolitan Belo Horizonte. Two distinct trends in mortality rates and accidents were identified. Most motorcycle deaths occurred after 7:00 PM. The study concludes that there is an urgent need to improve motorcycle and public transportation routes. PMID- 26872239 TI - [Ethnic disparities in the use of reproductive health services by indigenous and African-descendant Colombian women]. AB - The aim of this study in Colombia was to analyze the use of reproductive health services (prenatal care, childbirth, and postpartum) according to women's ethnicity, based on the National Demographic and Health Survey for 2010. Ethnicity was self-reported (indigenous, African-descendant, or neither), and logistic models were performed for each service. The use of reproductive health services was lower among indigenous and African-descendant Colombian women when compared to those that did not declare their ethnicity. According to the regression models, indigenous women showed lower odds of having an adequate number of prenatal visits (OR = 0.61), and the same was true for African descendant women. The same situation prevailed for institutional childbirth care: indigenous women (OR = 0.33) and African-descendant women (OR = 0.60); and postpartum follow-up: indigenous (OR = 0.80), African-descendant (OR = 0.80). In conclusion, there are inequities in the use of reproductive health services by women belonging to ethnic groups in Colombia, who should be targeted with government strategies to guarantee their right to health. PMID- 26872240 TI - [Psychosocial Care Centers for Children and Adolescents in Brazil: geographic distribution and user profile]. AB - Few Brazilian studies have addressed the use of mental health services for children and adolescents. This study aimed to characterize the national distribution of Psychosocial Care Centers for Children and Adolescents (CAPSi) and describe the patient profile in this age group between 2008 and 2012. An ecological study was carried out, using records from the Authorizations for High Complexity Procedures (APAC) system and the Brazilian National Registry of Healthcare Organizations (CNES). Socio-demographics and disease profile were analyzed. In 2014, 208 CAPSi were recorded in the CNES, distributed across 23 of Brazil's 27 states. Treatments included predominantly behavioral disorders (29.7%), developmental disorders (23.6%), and mental retardation (12.5%). CAPSi are insufficient and unequally distributed. The disease profile suggests the need for linkage between specialized mental health services and primary care, in addition to the inclusion of inter-sector work. PMID- 26872241 TI - Selective and Sensitive Detection of Heavy Metal Ions in 100% Aqueous Solution and Cells with a Fluorescence Chemosensor Based on Peptide Using Aggregation Induced Emission. AB - A fluorescent peptidyl chemosensor for the detection of heavy metal ions in aqueous solution as well as in cells was synthesized on the basis of the peptide receptor for the metal ions using an aggregation-induced emission fluorophore. The peptidyl chemosensor (1) bearing tetraphenylethylene fluorophore showed an exclusively selective turn-on response to Hg(2+) among 16 metal ions in aqueous buffered solution containing NaCl. The peptidyl chemosensor complexed Hg(2+) ions and then aggregated in aqueous buffered solution, resulting in the significant enhancement (OFF-On) of emissions at around 470 nm. The fluorescent sensor showed a highly sensitive response to Hg(2+), and about 1.0 equiv of Hg(2+) was enough for the saturation of the emission intensity change. The detection limit (5.3 nM, R(2) = 0.99) of 1 for Hg(2+) ions was lower than the maximum allowable level of Hg(2+) in drinking water by EPA. Moreover, the peptidyl chemosensor penetrated live cells and detected intracellular Hg(2+) ions by the turn-on response. PMID- 26872242 TI - Directional surface enhanced Raman scattering on gold nano-gratings. AB - Directional plasmon excitation and surface enhanced Raman scattering (SERS) emission were demonstrated for 1D and 2D gold nanostructure arrays deposited on a flat gold layer. The extinction spectrum of both arrays exhibits intense resonance bands that are redshifted when the incident angle is increased. Systematic extinction analysis of different grating periods revealed that this band can be assigned to a propagated surface plasmon of the flat gold surface that fulfills the Bragg condition of the arrays (Bragg mode). Directional SERS measurements demonstrated that the SERS intensity can be improved by one order of magnitude when the Bragg mode positions are matched with either the excitation or the Raman wavelengths. Hybridized numerical calculations with the finite element method and Fourier modal method also proved the presence of the Bragg mode plasmon and illustrated that the enhanced electric field of the Bragg mode is particularly localized on the nanostructures regardless of their size. PMID- 26872243 TI - Laparoscopic Total Mesorectal Excision with Enbloc Resection of Seminal Vesicle for Locally Advanced Rectal Adenocarcinoma. AB - Complete surgical resection remains the primary goal of rectal cancer surgeries. However, in 10%-20% patients, rectal tumors invade adjacent pelvic organs and resection of such organs is essential to achieve an R0 resection. Seminal vesicle is the most commonly involved organ in males. Although laparoscopic surgery has been found to be safe and feasible for rectal cancer surgeries, multivisceral resection is considered complex, and hence majority of these patients are offered open surgical resection. However, with improved surgical expertise as well as better laparoscopic equipment, surgeons have been attempting more complex rectal surgeries through the laparoscopic approach. We are delineating the technical details as well as initial results of laparoscopic total mesorectal excision with enbloc resection of seminal vesicle. PMID- 26872244 TI - Controlling an electrostatic repulsion by oppositely charged surfactants towards positively charged fluorescent gold nanoclusters. AB - A novel positively charged fluorescent gold nanocluster was successfully synthesized using the shortest cationic thiol, thiocholine. Effective control of electrostatic repulsion by the introduction of an anionic surfactant afforded a nanocluster that showed blue fluorescence emission. PMID- 26872245 TI - Further Advancements of CROES, a New Platform for Producing Clinical Evidence. PMID- 26872246 TI - Fetal cardiovascular hemodynamics in twin-twin transfusion syndrome. AB - Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic diamniotic (MCDA) pregnancies. It originates from unbalanced transfer of fluid and vasoactive mediators from one twin to its co-twin via placental anastomoses. This results in hypovolemia in the donor and hypervolemia and vasoconstriction in the recipient twin. Consequently, the recipient demonstrates cardiovascular alterations including atrioventricular valve regurgitation, diastolic dysfunction, and pulmonary stenosis/atresia that do not necessarily correlate with Quintero-stages. Selective fetoscopic laser photocoagulation of placental vascular anastomoses disrupts the underlying pathophysiology and usually improves cardiovascular function in the recipient with normalization of systolic and diastolic function within weeks after treatment. Postnatal studies have demonstrated early decreased arterial distensibility in ex-donor twins, but 10 year follow up is encouraging with survivors showing normal cardiovascular function after TTTS. However, prediction and appropriate early management of TTTS remain poor. Assessment of the cardiovascular system provides additional insight into the pathophysiology and severity of TTTS and may permit more targeted early surveillance of MCDA pregnancies in future. It should form an integral part of the diagnostic algorithm. PMID- 26872247 TI - Obsessive-Compulsive Disorder Related to Mycoplasma-Associated Autoimmune Encephalopathy with Basal Ganglia Involvement. PMID- 26872248 TI - The not face: A grammaticalization of facial expressions of emotion. AB - Facial expressions of emotion are thought to have evolved from the development of facial muscles used in sensory regulation and later adapted to express moral judgment. Negative moral judgment includes the expressions of anger, disgust and contempt. Here, we study the hypothesis that these facial expressions of negative moral judgment have further evolved into a facial expression of negation regularly used as a grammatical marker in human language. Specifically, we show that people from different cultures expressing negation use the same facial muscles as those employed to express negative moral judgment. We then show that this nonverbal signal is used as a co-articulator in speech and that, in American Sign Language, it has been grammaticalized as a non-manual marker. Furthermore, this facial expression of negation exhibits the theta oscillation (3-8 Hz) universally seen in syllable and mouthing production in speech and signing. These results provide evidence for the hypothesis that some components of human language have evolved from facial expressions of emotion, and suggest an evolutionary route for the emergence of grammatical markers. PMID- 26872250 TI - Controllable synthesis of Zn/Cd(ii) coordination polymers: dual-emissive luminescent properties, and tailoring emission tendency under varying excitation energies. AB - Based on a new asymmetric semi-rigid V-shaped tricarboxylate ligand 3-(2',3' dicarboxylphenoxy)benzoic acid (H3dpob), a series of zinc/cadmium(ii) coordination polymers, {[Cd(Hdpob)(H2O)3].H2O}n (1), [Cd(Hdpob)(bib)]n (2), [Zn(Hdpob)(bib)0.5]n (3), {[Cd1.5(dpob)(2,2'-bipy)].0.5H2O}2n (4) and {[Cd3(dpob)2(4,4'-bipy)2].3H2O}n (5) [bib = 1,4-bis(1-imidazolyl)benzene; 2,2' bipy = 2,2'-bipyridine; 4,4'-bipy = 4,4'-bipyridine], have been successfully synthesized via hydro(solvo)thermal reactions. 1 forms a three dimensional (3D) supramolecular structure linked by two types of intermolecular hydrogen bonds based on zig-zag 1D chains, whereas 2 and 3 are obtained with a similar 2D layer structure by the same ligands and further connected into a 3D structure through hydrogen bonds. 4 displays a homochiral 2D structure though two achiral ligands 2,2'-bipy and H3dpob, which contains right-handed helical infinite chains. 5 is a 3D structure containing 2D metal-pyridine layer motifs, which are further pillared by beaded dpob(3-) ligands to complete the structure and form a 6 connected pcu (primitive cubic) net. In DMSO solvent, 1-5 illustrate dual emission properties but have different low-energy emission (LE) intensities relatively. Extraordinarily, the difference resulting from central metals between 2 and 3 makes the intensity of LE dramatically enhanced and quenched. In this regard, the luminescence of 2 and 3 can be tuned between blue and green regions by varying the excitation light, and the tuning tendency can be tailored with inverse directions. Comparing their tunable-sensitivity to energy quantitatively, the theoretical calculation displays that 3 (4.29%) is little higher than 2 (3.59%) in a relative lower excitation wavelength zone. Meanwhile, five coordination polymers show distinct luminescence thermochromism in the solid state. When the temperature decreases from 298 K to 77 K, the red-shift from blue/green to the pure yellow light region is highlighted. The fantastic and unique luminescence phenomenon not only brings an insight into the synthesis of dual-emissive materials, but helps us to understand the luminescence behavior deeply as well. PMID- 26872249 TI - Instruction to forget leads [corrected] to emotional devaluation. AB - OBJECTIVE: The aim of this study was to investigate if the interaction between emotion and memory is bidirectional. Specifically we tested if intentional forgetting of words and faces would lead to their subsequent emotional devaluation. METHOD: In three experiments we combined an item-method directed forgetting paradigm with an emotional evaluation task. In addition, to test the general response bias hypothesis, we manipulated the forget instruction so that participants would associate a positive encoding affect with this condition. RESULTS: We found that intentionally forgotten words and faces were subsequently emotionally devaluated as compared with the to-be-remembered words and faces. Furthermore, this effect was replicated for words when we associated a positive instruction with the forget condition, which supports that the devaluation was memory specific. CONCLUSION: These findings suggest that the Distractor Devaluation effect previously reported in the attention field can be generalized to memory. This is one the first studies to show an influence of memory processes, namely forgetting, on emotion. PMID- 26872251 TI - Constructing a Catalytic Cycle for C-F to C-X (X = O, S, N) Bond Transformation Based on Gold-Mediated Ligand Nucleophilic Attack. AB - A tricoordinated gold(I) chloride complex, tBuXantphosAuCl, supported by a sterically bulky 9,9-dimethyl-4,5-bis(di-tert-butylphosphino)xanthene ligand (tBuXantphos) was synthesized. This complex features a remarkably longer Au-Cl bond length [2.632(1) A] than bicoordinated linear gold complexes (2.27-2.30 A) and tricoordinated XantphosAuCl [2.462(1) A]. Single-crystal X-ray diffraction analysis of a cocrystal of tBuXantphosAuCl and pentafluoronitrobenzene (PFNB) and UV-vis spectroscopic titration experiments revealed the existence of an anion-pi interaction between the Cl anion ligand and PFNB. Stoichiometric reaction between PFNB and tBuXantphosAuOtBu, after replacement of Cl by a more nucleophilic tBuO anion ligand, showed higher reactivity and para selectivity in the transformation of C-F to C-OtBu bond, distinctively different from that when only KOtBu was used (ortho selectivity) under the identical condition. Mechanistic studies including density functional theory calculations suggested a gold-mediated nucleophilic ligand attack of the C-F bond pathway via an SNAr process. On the basis of these results, using trimethylsilyl derivatives TMS-X (X = OMe, SEt, NEt2) as the nucleophilic ligand source and the fluorine acceptor, catalytic transformation of the C-F bond of aromatic substrates to the C-X (X = O, S, N) bond was achieved with tBuXantphosAuCl as the catalyst (up to 20 turnover numbers). PMID- 26872252 TI - Gremlin-1 C-Terminus Regulates Function of Macrophage Migration Inhibitory Factor (MIF). AB - BACKGROUND/AIMS: The counterbalance of macrophage migration inhibitory factor (MIF) and Gremlin-1 is a useful tool to predict the acuity of coronary artery disease (CAD) and plaque stability. Gremlin1 is an endogenous antagonist of MIF and therefore influences plaque vulnerability. This study was designed to elucidate the mechanistic basis determining the biophysical binding of Gremlin-1 to MIF. METHODS: An in silico model suggested that several charged C-terminal amino acids are crucial in mediating Gremlin-1/MIF-binding. We produced several single amino acid exchange mutants of Gremlin-1 by site-directed mutagenesis. These Gremlin-1 mutants were tested for their ability to reduce MIF effects on monocytes. RESULTS: We observed that the critical element of the Gremlin-1 molecule for regulating MIF-induced chemotactic activity lies at the C-terminal region. A single amino acid exchange of an arginine to an alanine residue is sufficient to abolish the antagonistic effect of Gremlin-1 on MIF. Therefore, the Gremlin-1 mutant R172A failed to reduce MIF-induced monocyte differentiation into macrophages. CONCLUSION: Gremlin-1 C-terminus is essential for antagonizing MIF effects. Our results could offer a novel strategy utilizing Gremlin-1 to target pro-inflammatory effects of MIF in various diseases. PMID- 26872253 TI - The Level of Anxiety and Depression in Dialysis Patients Undertaking Regular Physical Exercise Training--a Preliminary Study. AB - BACKGROUND/AIMS: The aim of the study was to evaluate the effects of a six-month physical training undertaken by haemodialysis (HD) patients, on the depression and anxiety. METHODS: Patients with end stage renal disease (ESRD) were recruited from the dialysis station at the Department of Nephrology and Transplantation Medicine in Wroclaw. Physical training took place at the beginning of the first 4 hours of dialysis, three times a week for six months. A personal questionnaire, Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) were used in the study. RESULTS: A total of 28 patients completed the study: 20 were randomised to endurance training and 8 were randomised to resistance training. Statistical analysis of depression and anxiety at the initial (t1) and final examination (t2) indicated a significant reduction in depression and anxiety, particularly anxiety as a trait (X2) in the whole study group. The change in anxiety as a state correlated with the disease duration, duration of dialysis and the initial level of anxiety as a state (t1X1). The change in anxiety as a trait significantly correlated with age and the initial level of anxiety (t1X2). CONCLUSIONS: Undertaking physical training during dialysis by patients with ESRD is beneficial in reducing their levels of anxiety and depression. Both resistance and endurance training improves mood, but only endurance training additionally results in anxiety reduction. PMID- 26872254 TI - Inhibition of Gastric Acid Secretion by H2 Receptor Antagonists Associates a Definite Risk of Enteric Peritonitis and Infectious Mortality in Patients Treated with Peritoneal Dialysis. AB - BACKGROUND: Evidences linking treatment with inhibitors of gastric acid secretion (IGAS) and an increased risk of serious infections are inconclusive, both in the population at large and in the particular case of patients with chronic kidney disease. We have undertaken an investigation to disclose associations between treatment with IGAS and infectious outcomes, in patients undergoing chronic Peritoneal Dialysis (PD). METHOD: Observational, historic cohort, single center design. Six hundred and ninety-one patients incident on PD were scrutinized for an association among treatment with IGAS (H2 antagonists H2A or proton pump inhibitors PPI) (main study variable), on one side, and the risks of enteric peritoneal infection (main outcome), overall peritoneal infection, and general and infectious mortality (secondary outcomes). We applied a three-step multivariate approach, based on classic Cox models (baseline variables), time dependent analyses and, when appropriate, competing risk analyses. MAIN RESULTS: The clinical characteristics of patients treated with H2A, PPI or none of these were significantly different. Multivariate analyses disclosed a consistently increased risk of enteric peritonitis in patients treated with IGAS (RR 1.65, 95% CI 1.08-2.55, p = 0.018, Cox). Stratified analysis indicated that patients treated with H2A, rather than those on PPI, supported the burden of this risk. Similar findings applied for the risk of infectious mortality. On the contrary, we were not able to detect any association among the study variables, on one side, and the general risks of peritonitis or mortality, on the other. CONCLUSIONS: Treatment with IGAS associates increased incidences of enteric peritonitis and infectious mortality, among patients on chronic PD. The association is clear in the case of H2A but less consistent in the case of PPI. Our results support the convenience of preferring PPI to H2A, for gastric acid inhibition in PD patients. PMID- 26872256 TI - Correction: Aerosols transmit prions to immunocompetent and immunodeficient mice. PMID- 26872255 TI - A Seroepidemiological Study of Serogroup A Meningococcal Infection in the African Meningitis Belt. AB - The pattern of epidemic meningococcal disease in the African meningitis belt may be influenced by the background level of population immunity but this has been measured infrequently. A standardised enzyme-linked immunosorbent assay (ELISA) for measuring meningococcal serogroup A IgG antibodies was established at five centres within the meningitis belt. Antibody concentrations were then measured in 3930 individuals stratified by age and residence from six countries. Seroprevalence by age was used in a catalytic model to determine the force of infection. Meningococcal serogroup A IgG antibody concentrations were high in each country but showed heterogeneity across the meningitis belt. The geometric mean concentration (GMC) was highest in Ghana (9.09 MUg/mL [95% CI 8.29, 9.97]) and lowest in Ethiopia (1.43 MUg/mL [95% CI 1.31, 1.57]) on the margins of the belt. The force of infection was lowest in Ethiopia (lambda = 0.028). Variables associated with a concentration above the putative protective level of 2 MUg/mL were age, urban residence and a history of recent vaccination with a meningococcal vaccine. Prior to vaccination with the serogroup A meningococcal conjugate vaccine, meningococcal serogroup A IgG antibody concentrations were high across the African meningitis belt and yet the region remained susceptible to epidemics. PMID- 26872259 TI - Nuclear Export of Pre-Ribosomal Subunits Requires Dbp5, but Not as an RNA Helicase as for mRNA Export. AB - The DEAD-box RNA-helicase Dbp5/Rat8 is known for its function in nuclear mRNA export, where it displaces the export receptor Mex67 from the mRNA at the cytoplasmic side of the nuclear pore complex (NPC). Here we show that Dbp5 is also required for the nuclear export of both pre-ribosomal subunits. Yeast temperature-sensitive dbp5 mutants accumulate both ribosomal particles in their nuclei. Furthermore, Dbp5 genetically and physically interacts with known ribosomal transport factors such as Nmd3. Similar to mRNA export we show that also for ribosomal transport Dbp5 is required at the cytoplasmic side of the NPC. However, unlike its role in mRNA export, Dbp5 does not seem to undergo its ATPase cycle for this function, as ATPase-deficient dbp5 mutants that selectively inhibit mRNA export do not affect ribosomal transport. Furthermore, mutants of GLE1, the ATPase stimulating factor of Dbp5, show no major ribosomal export defects. Consequently, while Dbp5 uses its ATPase cycle to displace the export receptor Mex67 from the translocated mRNAs, Mex67 remains bound to ribosomal subunits upon transit to the cytoplasm, where it is detectable on translating ribosomes. Therefore, we propose a model, in which Dbp5 supports ribosomal transport by capturing ribosomal subunits upon their cytoplasmic appearance at the NPC, possibly by binding export factors such as Mex67. Thus, our findings reveal that although different ribonucleoparticles, mRNAs and pre-ribosomal subunits, use shared export factors, they utilize different transport mechanisms. PMID- 26872258 TI - Mid- to Long-Term Outcomes of Cervical Disc Arthroplasty versus Anterior Cervical Discectomy and Fusion for Treatment of Symptomatic Cervical Disc Disease: A Systematic Review and Meta-Analysis of Eight Prospective Randomized Controlled Trials. AB - PURPOSE: This study aimed to investigate the mid- to long-term outcomes of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for the treatment of 1-level or 2-level symptomatic cervical disc disease. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify relevant randomized controlled trials that reported mid- to long-term outcomes (at least 48 months) of CDA versus ACDF. All data were analyzed by Review Manager 5.3 software. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous variables. The weighted mean difference (WMD) and 95%CIs were calculated for continuous variables. A random effect model was used for heterogeneous data; otherwise, a fixed effect model was used. RESULTS: Eight prospective randomized controlled trials (RCTs) were retrieved in this meta-analysis, including 1317 and 1051 patients in CDA and ACDF groups, respectively. Patients after an ACDF had a significantly lower rate of follow-up than that after CDA. Pooled analysis showed patients in CDA group achieved significantly higher rates of overall success, Neck Disability Index (NDI) success, neurological success and significantly lower rates of implant/surgery-related serious adverse events and secondary procedure compared with that in ACDF group. The long-term functional outcomes (NDI, Visual Analog Scale (VAS) neck and arm pain scores, the Short Form 36 Health Survey physical component score (SF-36 PCS)), patient satisfaction and recommendation, and the incidence of superior adjacent segment degeneration also favored patients in CDA group with statistical difference. Regarding inferior adjacent segment degeneration, patients in CDA group had a lower rate without statistical significance. CONCLUSIONS: This meta-analysis showed that cervical disc arthroplasty was superior over anterior discectomy and fusion for the treatment of symptomatic cervical disc disease in terms of overall success, NDI success, neurological success, implant/surgery-related serious adverse events, secondary procedure, functional outcomes, patient satisfaction and recommendation, and superior adjacent segment degeneration. PMID- 26872260 TI - Mixed Compound of DCPTA and CCC Increases Maize Yield by Improving Plant Morphology and Up-Regulating Photosynthetic Capacity and Antioxidants. AB - DCPTA (2-diethylaminoethyl-3, 4-dichlorophenylether) and CCC (2 chloroethyltrimethyl- ammonium chloride) have a great effect on maize growth, but applying DCPTA individually can promote the increase of plant height, resulting in the rise of lodging percent. Plant height and lodging percent decrease in CCC treated plants, but the accumulation of biomass reduce, resulting in yield decrease. Based on the former experiments, the performance of a mixture which contained 40 mg DCPTA and 20 mg CCC as active ingredients per liter of solution, called PCH was tested with applying 40mg/L DCPTA and 20mg/L CCC individually. Grain yield, yield components, internode characters, leaf area per plant, plant height and lodging percent as well as chlorophyll content, chlorophyll fluorescence, enzymatic antioxidants, membranous peroxide and organic osmolyte were analyzed in two years (2011 and 2012), using maize hybrid, Zhengdan 958 (ZD 958) at density of 6.75 plants m-2. CCC, DCPTA and PCH were sprayed on the whole plant leaves at 7 expanded leaves stage and water was used as control. Compared to control, PCH significantly increased grain yield (by 9.53% and 6.68%) from 2011 to 2012. CCC significantly decreased kernel number per ear (by 6.78% and 5.69%) and thousand kernel weight (TKW) (by 8.57% and 6.55%) from 2011 to 2012. Kernel number per ear and TKW increased in DCPTA-treated and PCH-treated plants, but showed no significant difference between them. In CCC-treated and PCH-treated plants, internode length and plant height decreased, internode diameter increased, resulting in the significant decline of lodging percent. With DCPTA application, internode diameter increased, but internode length and plant height increased at the same time, resulting in the augment of lodging percent. Bending strength and puncture strength were increased by applying different plant growth regulators (PGRs). In PCH-treated plants, bending strength and puncture strength were greater than other treatments. Compared to control, the bending strength of 3rd internode was increased by 14.47% in PCH-treated plants in 2011, increased by 18.40% in 2012, and the difference was significant. Puncture strength of 1st, 3rd and 5th internode was increased by 37.25%, 29.17% and 26.09% in 2011 and 34.04%, 25% and 23.68% in 2012, compared to control. Leaf area and dry weight per plant reduced significantly in CCC-treated plants, increased in DCPTA-treated and PCH treated plants from 2011 to 2012. Chlorophyll content and chlorophyll fluorescence improved with CCC and DCPTA application. Due to the additive effect of DCPTA and CCC, PCH showed the significant effect on chlorophyll content and chlorophyll fluorescence. Compared to control, total enzyme activity (SOD, POD, CAT, APX and GR) and soluble protein content increased, malonaldehyde (MDA) and hydrogen peroxide (H2O2) content reduced in PCH-treated plants. The transportation of soluble sugar from leaf to kernel improved significantly at the late silking stage. The research provided the way for the further use of DCPTA and CCC into the production practice. PMID- 26872257 TI - Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes. AB - The 16p11.2 600 kb BP4-BP5 deletion and duplication syndromes have been associated with developmental delay; autism spectrum disorders; and reciprocal effects on the body mass index, head circumference and brain volumes. Here, we explored these relationships using novel engineered mouse models carrying a deletion (Del/+) or a duplication (Dup/+) of the Sult1a1-Spn region homologous to the human 16p11.2 BP4-BP5 locus. On a C57BL/6N inbred genetic background, Del/+ mice exhibited reduced weight and impaired adipogenesis, hyperactivity, repetitive behaviors, and recognition memory deficits. In contrast, Dup/+ mice showed largely opposite phenotypes. On a F1 C57BL/6N * C3B hybrid genetic background, we also observed alterations in social interaction in the Del/+ and the Dup/+ animals, with other robust phenotypes affecting recognition memory and weight. To explore the dosage effect of the 16p11.2 genes on metabolism, Del/+ and Dup/+ models were challenged with high fat and high sugar diet, which revealed opposite energy imbalance. Transcriptomic analysis revealed that the majority of the genes located in the Sult1a1-Spn region were sensitive to dosage with a major effect on several pathways associated with neurocognitive and metabolic phenotypes. Whereas the behavioral consequence of the 16p11 region genetic dosage was similar in mice and humans with activity and memory alterations, the metabolic defects were opposite: adult Del/+ mice are lean in comparison to the human obese phenotype and the Dup/+ mice are overweight in comparison to the human underweight phenotype. Together, these data indicate that the dosage imbalance at the 16p11.2 locus perturbs the expression of modifiers outside the CNV that can modulate the penetrance, expressivity and direction of effects in both humans and mice. PMID- 26872261 TI - CTGF/CCN2 Postconditioning Increases Tolerance of Murine Hearts towards Ischemia Reperfusion Injury. AB - BACKGROUND AND PURPOSE: Previous studies of ischemia-reperfusion injury (IRI) in hearts from mice with cardiac-restricted overexpression of CCN2 have shown that CCN2 increases tolerance towards IRI. The objectives of this study were to investigate to what extent post-ischemic administration of recombinant human CCN2 (rhCCN2) would limit infarct size and improve functional recovery and what signaling pathways are involved. EXPERIMENTAL APPROACH: Isolated mice hearts were perfused ad modum Langendorff, subjected to no-flow, global ischemia, and subsequently, exposed to mammalian cell derived, full-length (38-40kDa) rhCCN2 (250 nM) or vehicle during the first 15 min of a 60 min reperfusion period. KEY RESULTS: Post-ischemic administration of rhCCN2 resulted in attenuation of infarct size from 58 +/- 4% to 34 +/- 2% (p < 0.001) which was abrogated by concomitant administration of the PI3 kinase inhibitor LY294002 (45 +/- 3% vs. 50 +/- 3%, ns). In congruence with reduction of infarct size rhCCN2 also improved recovery of left ventricular developed pressure (p < 0.05). Western blot analyses of extracts of ex vivo-perfused murine hearts also revealed that rhCCN2 evoked concentration-dependent increase of cardiac phospho-GSK3beta (serine-9) contents. CONCLUSIONS AND IMPLICATIONS: We demonstrate that post-ischemic administration of rhCCN2 increases the tolerance of ex vivo-perfused murine hearts to IRI. Mechanistically, this postconditioning effect of rhCCN2 appeared to be mediated by activation of the reperfusion injury salvage kinase pathway as demonstrated by sensitivity to PI3 kinase inhibition and increased CCN2-induced phosphorylation of GSK3beta (Ser-9). Thus, the rationale for testing rhCCN2-mediated post ischemic conditioning of the heart in more complex models is established. PMID- 26872262 TI - High-Pitch CT Pulmonary Angiography in Third Generation Dual-Source CT: Image Quality in an Unselected Patient Population. AB - OBJECTIVES: To investigate the feasibility of high-pitch CT pulmonary angiography (CTPA) in 3rd generation dual-source CT (DSCT) in unselected patients. METHODS: Forty-seven patients with suspected pulmonary embolism underwent high-pitch CTPA on a 3rd generation dual-source CT scanner. CT dose index (CTDIvol) and dose length product (DLP) were obtained. Objective image quality was analyzed by calculating signal-to-noise-ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality on the central, lobar, segmental and subsegmental level was rated by two experienced radiologists. RESULTS: Median CTDI was 8.1 mGy and median DLP was 274 mGy*cm. Median SNR was 32.9 in the central and 31.9 in the segmental pulmonary arteries. CNR was 29.2 in the central and 28.2 in the segmental pulmonary arteries. Median image quality was "excellent" in central and lobar arteries and "good" in subsegmental arteries according to both readers. Segmental arteries varied between "excellent" and "good". Image quality was non diagnostic in one case (2%), beginning in the lobar arteries. Thirteen patients (28%) showed minor motion artifacts. CONCLUSIONS: In third-generation dual-source CT, high-pitch CTPA is feasible for unselected patients. It yields excellent image quality with minimal motion artifacts. However, compared to standard-pitch cohorts, no distinct decrease in radiation dose was observed. PMID- 26872264 TI - Protective Effect of Naringenin against Lipopolysaccharide-Induced Acute Lung Injury in Rats. AB - BACKGROUND/AIMS: Lipopolysaccharide (LPS) induces acute lung injury (ALI) through oxidative stress and inflammation. Naringenin exerts antioxidant and anti inflammatory effects. The possible protective effect of naringenin was investigated against ALI induced by LPS in rats. METHODS: Rats received a single injection of LPS (5 mg/kg, i.v.). Naringenin was given for 4 consecutive days, at 2 doses (50 and 100 mg/kg/day, p.o.), starting 3 days before LPS administration. RESULTS: LPS significantly increased wet/dry lung weight ratio, malondialdehyde, nitric oxide (NO), interleukin-6, and myeloperoxidase activity in the lung tissues. Naringenin, particularly the higher dose, significantly ameliorated the LPS-induced changes in the measured parameters. Also, naringenin markedly reduced the histopathological lung tissue injury that resulted from LPS. Naringenin significantly decreased the LPS-induced expression of nuclear factor-x03BA;B, inducible NO synthase, tumor necrosis factor-alpha, caspase-3, and significantly increased heat shock protein 70 expression in the lungs. CONCLUSION: Naringenin significantly protected against LPS-induced ALI in rats through its anti inflammatory, antioxidant, antinitrosative, and antiapoptotic effects. PMID- 26872265 TI - Correction: Binge Ethanol Prior to Traumatic Brain Injury Worsens Sensorimotor Functional Recovery in Rats. PMID- 26872263 TI - Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature. AB - End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10-11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes. PMID- 26872266 TI - Thrombin Generation in Zebrafish Blood. AB - To better understand hypercoagulability as an underlying cause for thrombosis, the leading cause of death in the Western world, new assays to study ex vivo coagulation are essential. The zebrafish is generally accepted as a good model for human hemostasis and thrombosis, as the hemostatic system proved to be similar to that in man. Their small size however, has been a hurdle for more widespread use in hemostasis related research. In this study we developed a method that enables the measurement of thrombin generation in a single drop of non-anticoagulated zebrafish blood. Pre-treatment of the fish with inhibitors of FXa and thrombin, resulted in a dose dependent diminishing of thrombin generation, demonstrating the validity of the assay. In order to establish the relationship between whole blood thrombin generation and fibrin formation, we visualized the resulting fibrin network by scanning electron microscopy. Taken together, in this study we developed a fast and reliable method to measure thrombin generation in whole blood collected from a single zebrafish. Given the similarities between coagulation pathways of zebrafish and mammals, zebrafish may be an ideal animal model to determine the effect of novel therapeutics on thrombin generation. Additionally, because of the ease with which gene functions can be silenced, zebrafish may serve as a model organism for mechanistical research in thrombosis and hemostasis. PMID- 26872267 TI - Kinetics of Indigenous Nitrate Reducing Sulfide Oxidizing Activity in Microaerophilic Wastewater Biofilms. AB - Nitrate decreases sulfide release in wastewater treatment plants (WWTP), but little is known on how it affects the microzonation and kinetics of related microbial processes within the biofilm. The effect of nitrate addition on these properties for sulfate reduction, sulfide oxidation, and oxygen respiration were studied with the use of microelectrodes in microaerophilic wastewater biofilms. Mass balance calaculations and community composition analysis were also performed. At basal WWTP conditions, the biofilm presented a double-layer system. The upper microaerophilic layer (~300 MUm) showed low sulfide production (0.31 MUmol cm-3 h-1) and oxygen consumption rates (0.01 MUmol cm-3 h-1). The anoxic lower layer showed high sulfide production (2.7 MUmol cm-3 h-1). Nitrate addition decreased net sulfide production rates, caused by an increase in sulfide oxidation rates (SOR) in the upper layer, rather than an inhibition of sulfate reducing bacteria (SRB). This suggests that the indigenous nitrate reducing sulfide oxidizing bacteria (NR-SOB) were immediately activated by nitrate. The functional vertical structure of the biofilm changed to a triple-layer system, where the previously upper sulfide-producing layer in the absence of nitrate split into two new layers: 1) an upper sulfide-consuming layer, whose thickness is probably determined by the nitrate penetration depth within the biofilm, and 2) a middle layer producing sulfide at an even higher rate than in the absence of nitrate in some cases. Below these layers, the lower net sulfide-producing layer remained unaffected. Net SOR varied from 0.05 to 0.72 MUmol cm-3 h-1 depending on nitrate and sulfate availability. Addition of low nitrate concentrations likely increased sulfate availability within the biofilm and resulted in an increase of both net sulfate reduction and net sulfide oxidation by overcoming sulfate diffusional limitation from the water phase and the strong coupling between SRB and NR-SOB syntrophic relationship. PMID- 26872269 TI - Kernel Manifold Alignment for Domain Adaptation. AB - The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across domains and data synthesis. To authors' knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational efficiency, and discuss the generalization performance of KEMA under Rademacher principles of stability. Aligning multimodal data with KEMA reports outstanding benefits when used as a data pre-conditioner step in the standard data analysis processing chain. KEMA exhibits very good performance over competing methods in synthetic controlled examples, visual object recognition and recognition of facial expressions tasks. KEMA is especially well-suited to deal with high-dimensional problems, such as images and videos, and under complicated distortions, twists and warpings of the data manifolds. A fully functional toolbox is available at https://github.com/dtuia/KEMA.git. PMID- 26872268 TI - Stress during Adolescence Alters Palatable Food Consumption in a Context Dependent Manner. AB - Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences. PMID- 26872271 TI - Dismantlable Thermosetting Adhesives Composed of a Cross-Linkable Poly(olefin sulfone) with a Photobase Generator. AB - A novel photodetachable adhesive was prepared using a photodepolymerizable cross linked poly(olefin sulfone). A mixture of a cross-linkable poly(olefin sulfone), a cross-linking reagent, and a photobase generator functioned as a thermosetting adhesive and exhibited high adhesive strength on quartz plates comparable to that obtained for commercially available epoxy adhesives. The cured resin was stable in the absence of UV light irradiation but completely lost its adhesive strength upon exposure of glued quartz plates to UV light in conjunction with heating to 100 degrees C. PMID- 26872270 TI - The Role of Endothelin System in Renal Structure and Function during the Postnatal Development of the Rat Kidney. AB - Renal development in rodents, unlike in humans, continues during early postnatal period. We aimed to evaluate whether the pharmacological inhibition of Endothelin system during this period affects renal development, both at structural and functional level in male and female rats. Newborn rats were treated orally from postnatal day 1 to 20 with vehicle or bosentan (Actelion, 20 mg/kg/day), a dual endothelin receptor antagonist (ERA). The animals were divided in 4 groups: control males, control females, ERA males and ERA females. At day 21, we evaluated renal function, determined the glomerular number by a maceration method and by morphometric analysis and evaluated possible structural renal alterations by three methods: -Smooth muscle actin (alpha-SMA) immunohistochemistry, Masson's trichrome and Sirius red staining. The pharmacological inhibition of Endothelin system with a dual ERA during the early postnatal period of the rat did not leads to renal damage in the kidneys of male and female rats. However, ERA administration decreased the number of glomeruli, the juxtamedullary filtration surface area and the glomerular filtration rate and increased the proteinuria. These effects could predispose to hypertension or renal diseases in the adulthood. On the other hand, these effects were more pronounced in male rats, suggesting that there are sex differences that could be greater later in life. These results provide evidence that Endothelin has an important role in rat renal postnatal development. However these results do not imply that the same could happen in humans, since human renal development is complete at birth. PMID- 26872272 TI - Endocytic control of signaling at the plasma membrane. AB - Signaling is regulated by endocytosis at multiple levels along endocytic routes. Endocytic control of signaling starts already at the plasma membrane, where cells employ different mechanisms to finely tune the type and strength of signals emanating from the cell surface. Here, we will review some of the most recently described endocytic mechanisms controlling signaling at the plasma membrane, through the regulation of internalization dynamics and through the integration of different internalization pathways triggered by canonical chemical stimuli or physical forces. PMID- 26872273 TI - Congenital factor XI and factor VII deficiencies assure an apparent opposite protection against arterial or venous thrombosis: An intriguing observation. AB - OBJECTIVE: To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency. PATIENTS AND METHODS: Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods. RESULTS: Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively. CONCLUSIONS: Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications. PMID- 26872274 TI - Molecular Detection of Tick-Borne Rickettsiales in Goats and Sheep from Southeastern China. AB - Members from Rickettsiales such as Anaplasma phagocytophilum, Ehrlichia chaffeensis, and some spotted fever group (SFG) Rickettsiae are important tick borne pathogens. One hundred goats and sheep from southeastern China were examined for the presence of Anaplasma, E. chaffeensis, and SFG Rickettsiae by PCR. A. phagocytophilum, Anaplasma bovis, and Anaplasma centrale were detected in 15, 49, and 16 samples, respectively. The A. phagocytophilum and A. centrale were highly homologous to strains from Japanese sika deer and Japanese cattle, respectively, whereas a diversity of A. bovis sequences were detected. New genetic variants of Anaplasma close to A. centrale have been revealed. No Ehrlichia was detected in this study. The presence of SFG Rickettsiae was determined in 26 samples. The coinfection with more than two pathogens tested in this study was as high as 29%. This study has molecularly characterized the circulation of Anaplasma and Rickettsiae in goats and sheep in southeastern China, which highlights the risk of contracting the pathogens upon tick exposure. PMID- 26872275 TI - Microsurgical Treatment of Meningiomas in the Torcular Herophili Region. AB - The Torcular Herophili region of the brain is anatomically complex, and surgery in this area requires much skill and care. Retrospective analysis on 35 cases of meningiomas in the Torcular Herophili region treated by microsurgery and confirmed by pathology. Tumor resection range was evaluated using the Simpson grading criteria. Postoperative complications and tumor recurrence were evaluated. Patients were followed up. The Karnofsky performance status was used to evaluate neurologic functions. Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) revealed the extent of disease in all patients. Simpson level I excision was done in 27 patients, level II in 5 patients, and level IV in 3 patients. Gamma knife treatment after surgery was performed in 3 patients. Symptoms of increased intracranial pressure were relieved after surgery. No patient died, and no patient suffered from any relevant operative complications and disabilities. Pathology reported typical meningioma (World Health Organization [WHO] level I) in 32 patients, and atypical meningioma (WHO level II) in 3 patients. Thirty-two patients were followed up for 0.5 to 5 years: 1 patient relapsed 2 years after operation (Simpson level IV excision), and 2 patients relapsed 3 years after operation (one Simpson level I and one level II). These results indicated that MRV should be performed to confirm the exact relationship between the tumor and venous sinus. The operative approach should be planned according to the MRI results, and the venous sinus should be preserved. Gamma knife might be a beneficial auxiliary treatment of meningioma in the Torcular Herophili region. PMID- 26872276 TI - Surgical Management of a Giant Residual Mandibular Cyst. PMID- 26872277 TI - Importance of Imaging Examinations to Planning the Removal of a Foreign Body From the Tongue. PMID- 26872278 TI - Effect of Porous Titanium Granules on Bone Regeneration and Primary Stability in Maxillary Sinus: A Human Clinical, Histomorphometric, and Microcomputed Tomography Analyses. AB - The aim of this randomized controlled study was to comparatively analyze the new bone (NB), residual bone, and graft-bone association in bone biopsies retrieved from augmented maxillary sinus sites by histomorphometry and microcomputed tomography (MicroCT) in a split-mouth model to test the efficacy of porous titanium granules (PTG) in maxillary sinus augmentation. Fifteen patients were included in the study and each patient was treated with bilateral sinus augmentation procedure using xenograft (equine origine, granule size 1000-2000 MUm) and xenograft (1 g) + PTG (granule size 700-1000 MUm, pore size >50 MUm) (1 g), respectively. After a mean of 8.4 months, 30 bone biopsies were retrieved from the implant sites for three-dimensional MicroCT and two-dimensional histomorphometric analyses. Bone volume and vital NB percentages were calculated. Immediate after core biopsy, implants having standard dimensions were placed and implant stability quotient values were recorded at baseline and 3 months follow up. There were no significant differences between groups according to residual bone height, residual bone width, implant dimensions, and implant stability quotient values (baseline and 3 months). According to MicroCT and two-dimensional histomorphometric analyses, the volume of newly formed bone was 57.05% and 52.67%, and 56.5% and 55.08% for xenograft + PTG and xenograft groups, respectively. No statistically significant differences found between groups according to NB percentages and higher Hounsfield unit values were found for xenograft + PTG group. The findings of the current study supports that PTG, which is a porous, permanent nonresorbable bone substitute, may have a beneficial osteoconductive effect on mechanical strength of NB in augmented maxillary sinus. PMID- 26872279 TI - Does Freeze-Thawing Influence the Effects of Platelet Concentrates? An In Vitro Study on Human Adipose-Derived Stem Cells. AB - Human adipose-derived stem cells (hASCs) have been proposed as a possible therapy for tissue regeneration in aesthetic, plastic, and reconstructive surgery. Today, platelet concentrates are used in a wide range of disciplines, but their storage has become a controversial aspect. The purpose of this in vitro study was to evaluate the effect of plasma rich in growth factors (PRGF), after a freeze thawing cycle, on the proliferation and biological activity of progenitor cells involved in soft tissue healing. Different formulations of activated PRGF were added to hASCs cultured in serum-free medium. Cell proliferation was assessed by MTT test and cell count up to 7 and 12-day incubation. Osteo-differentiation ability of hASCs was also tested after 7 and 14-day incubation by alkaline phosphatase assay. The effects of 4 PRGF preparations (fresh/frozen and with/without platelets) were compared with corresponding formulations of plasma poor in growth factors and with standard medium. hASCs cultured in the presence of platelet concentrates increased proliferation rate with respect to cells grown in standard medium without significant differences among all the tested plasma formulations on cell viability up to 12 days of culture. PRGF activity is preserved after cryopreservation and platelet-rich preparations promoted osteo differentiation of hASCs at day 7. In conclusion, PRGF supports the proliferation and the differentiation of progenitor cells in vitro also when applied after cryopreservation. Platelet concentrates, either alone or in combination with mesenchymal stem cells, might be a valuable tool in the field of tissue regeneration. PMID- 26872280 TI - The Role of Fine Needle Aspiration in the Diagnosis of Parotid Gland Tumors: Correlation With Preoperative Computerized Tomography Tumor Size. AB - The role of fine needle aspiration cytology (FNAC) in the diagnosis of parotid gland masses is still controversial, regarding its sensitivity and specificity that vary between 41% and 100% and between 86% and 100% respectively.The aim of this study was to identify the specificity and sensitivity of FNAC of parotid gland tumors in relation to the tumor size as characterized preoperatively by computer tomography. The medical files of 79 patients whom were referred to the MaxilloFacila Surgery Department, Rambam medical center, over a 10.5-year period (2000-2010) were analyzed retrospectively.The extensity of the operation was determined by the location of the tumor as presented in computed tomography (CT) radiography, and preoperative FNAC examination.The majority of the masses were located in the superficial lobe (88.52%), and only 11.48% of the patients were located in the deep lobe (8:1 ratio). FNAC results were nondiagnostic in 7 patients (8.86%), 62 patients were diagnosed as inflammatory and benign lesion in (78.48%), malignant tumors were diagnosed in 10 patients (12.65%).The sensitivity in our study was 90%, the specificity was 98%, positive predictive value was 90%, negative predictive value was 98%, and diagnostic accuracy was 88%. The positive predictive value was 90%, the negative predictive value was 98%.Analyzing the effect of the preoperative CT size upon the accuracy of the FNAC diagnosis, we found that lesion with preoperative CT size greater than 24 mm has a more accurate FNAC result (P = 0.034). PMID- 26872282 TI - Hemangioma of the Zygomatic Bone. AB - Benign masses arising from facial bones have been reported several times in the literature. Hemangiomas are one of the uncommon benign tumors. In this study, the authors aimed to present a rare patient of zygomatic intraosseos hemangioma and their management. A 40-year-old woman with a mass in her left lateral cantus admitted to our clinic. Preoperative computed tomography and magnetic resonance imaging revealed an osseos mass in her left zygoma. The authors conclude that it should be kept in mind that although they are very rare benign tumors, intraosseos hemangiomas can cause facial masses. Meticulous radiologic examination can give important clues for differential diagnosis before the surgery. PMID- 26872281 TI - Correlation Between Cephalometric Measures and End-of-Treatment Facial Attractiveness. AB - Sixty-nine experienced Chinese orthodontists evaluated 108 Chinese patients' facial attractiveness from set of photographs (frontal, lateral, and frontal smiling photos) taken at the end of orthodontic treatment. These 108 patients, which contained an equal number of patients with Class I, II, and III malocclusion, were randomly selected from 6 orthodontic treatment centers throughout China. Spearman rank-order correlation coefficients (rs) analyses were performed to examine agreement in ranking between all judge pairs. Pearson correlation and multivariate regression were performed to examine the correlation between cephalometric measures and end-of-treatment Photo Attractiveness Rank.96.68% judge pairs showed moderate correlated (+0.4 <= rs < +0.7) subjective rankings. Cephalometric measures significantly correlated with end-of-treatment Photo Attractiveness Rank included interincisal angle (r = 0.330, P < 0.05), L1/MP degrees (r = 0.386, P < 0.05), L1-NBmm (r = 0.451, P < 0.01), L1/NB degrees (r = 0.374, P < 0.05), and profile angle (r = 0.353, P < 0.05) in Class I patients with an explained variance of 32.8%, and ANB angle (r = 0.432, P < 0.01), angle of convexity (r = 0.448, P < 0.01), profile angle (r = 0.488, P < 0.01), Li to E-line (r = 0.374, P < 0.05), Li to B-line (r = 0.543, P < 0.01), and Z angle (r = 0.543, P < 0.01) in Class II patient with an explained variance of 43.3%.There was less association than expected between objective measurements on the lateral cephalograms and clinicians' rankings of facial attractiveness on clinical photography in Chinese patients. Straight-stand lower incisor was desired for facial attractiveness of Class I malocclusion; and sagittal relationship and lip prominence influence the esthetics of Class II malocclusion in Chinese population. PMID- 26872283 TI - Comminuted Frontal Sinus Fracture Reconstructed With Titanium Mesh. AB - Frontal sinus fractures (FSF) are relatively uncommon maxillofacial injuries. The most common cause of FSF is motor vehicle accidents with 62% percentage. Management of FSF depends on type of fracture, associated injuries, and involvement of naso-frontal duct. In this report, the authors presented a patient with comminuted fracture of anterior wall of frontal sinus reconstructed with titanium mesh. A 40-year-old man presented with depression of the frontal bone, facial pain, and epistaxis consisting of a motor vehicle accident. Computerized tomography scan revealed multiple comminuted fractures of anterior wall of frontal sinus and fractures of left orbital medial and superior walls. Titanium mesh was used for reconstruction. Postoperative course was uneventful. The titanium mesh, which is easy to handle with no complications, may provide excellent frontal contour after comminuted anterior wall fractures. PMID- 26872284 TI - Curative Transvenous Onyx Embolization of a Maxillary Arteriovenous Malformation in a Child: Report of a New Technique. AB - Endovascular management of maxillary arteriovenous malformation (AVMs) can be complex. Transarterial, transvenous, and direct puncture embolization has been described. The authors report the case of a 9-year-old girl with a hemorrhagic maxillary AVM, which has been treated by transvenous embolization after failure of transarterial embolization. The venous pouch was catheterized with a detachable tip microcatheter and occluded by slow Onyx injection. Onyx filled the pouch and retrogradely reached some arterial feeders, achieving complete occlusion. Bleeding episode ceased and at 6 months follow-up no recurrence was found. Maxillary AVMs can be successfully treated by transvenous Onyx embolization. PMID- 26872285 TI - Schwannoma Originating From the Nasal Septum. AB - Schwannomas are benign tumors deriving from Schwann cells of the nerve sheath. They can occur in all parts of the body. Involvement of the nasal septum is quite rare, with only few cases having been reported in the literature. The authors present a patient with a unilateral tumor diagnosed as a schwannoma of the nasal septum. PMID- 26872286 TI - Pharmacotherapy follow-up of key points in the safety of oral antineoplastic agents. AB - We assessed the impact of a pharmacotherapy follow-up programme on key safety points [adverse events (AE) and drug administration] in outpatients treated with oral antineoplastic agents (OAA). We performed a comparative, interventional, quasi-experimental study of outpatients treated with OAA in a Spanish hospital to compare pre-intervention group patients (not monitored by pharmacists during 2011) with intervention group patients (prospectively monitored by pharmacists during 2013). AE data were collected from medical records. Follow-up was 6 months, and 249 patients were included (pre-intervention, 115; intervention, 134). After the first month, AE were detected in 86.5% of patients in the pre intervention group and 80.6% of patients in the intervention group, P = 0.096. During the remaining months, 79.0% patients had at least one AE in the pre intervention group compared with 78.0% in the intervention group, P = 0.431. AE were more prevalent with sorafenib and sunitinib. In total, 173 drug interactions were recorded (pre-intervention, 80; intervention, 93; P = 0.045). Drug interactions were more frequent with erlotinib and gefitinib; food interactions were more common with sorafenib and pazopanib. Our follow-up of cancer outpatients revealed a reduction in severe AE and major drug interactions, thus helping health professionals to monitor the safety of OAA. PMID- 26872287 TI - Coenzyme Q10 Exerts Anti-Inflammatory Activity and Induces Treg in Graft Versus Host Disease. AB - The objective of this study was to determine whether coenzyme Q10 (CoQ10) can reduce the severity of graft versus host disease (GVHD) by inducing regulatory T cells (Tregs). CoQ10 or vehicle was orally administrated once a day for 22 days to mice with GVHD. We measured the alloresponse of the T cells and the GVHD clinical scores. Real-time polymerase chain reaction was used to examine messenger RNA (mRNA) level. Flow cytometry and enzyme-linked immunosorbent assay were used to evaluate protein expression. CoQ10 reduced the T-cell alloresponse and the expression of interferon (IFN)-gamma and interleukin (IL)-17. The severity of GVHD and gene expressions of IL-6 and tumor necrosis factor (TNF) alpha decreased with CoQ10 treatment. Furthermore, CoQ10 promoted weight gain and survival in GVHD mice. Flow cytometry revealed that CoQ10 dose dependently induced Treg differentiation, but FK506, an immunosuppressive drug, decreased Treg differentiation dose dependently. In conclusion, CoQ10 downregulates the alloreactivity of T cells and reduces GVHD severity, enhancing the differentiation of Tregs. PMID- 26872290 TI - Placing Design and Delivery at the Forefront of Physical Activity Intervention. PMID- 26872289 TI - Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study. AB - AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score >=64), physical activity level (estimated energy expenditure >=170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, >=1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia. PMID- 26872291 TI - Time-Dependent Effects of Cardiovascular Exercise on Memory. AB - We present new evidence supporting the hypothesis that the effects of cardiovascular exercise on memory can be regulated in a time-dependent manner. When the exercise stimulus is coupled temporally with specific phases of the memory formation process, a single bout of cardiovascular exercise may be sufficient to improve memory. PMID- 26872293 TI - Psychological burden at the time of diagnosis among Mexican breast cancer patients. PMID- 26872294 TI - Breaking up prolonged sitting time with walking does not affect appetite or gut hormone concentrations but does induce an energy deficit and suppresses postprandial glycaemia in sedentary adults. AB - Breaking up periods of prolonged sitting can negate harmful metabolic effects but the influence on appetite and gut hormones is not understood and is investigated in this study. Thirteen sedentary (7 female) participants undertook three 5-h trials in random order: (i) uninterrupted sitting (SIT), (ii) seated with 2-min bouts of light-intensity walking every 20 min (SIT + LA), and (iii) seated with 2 min bouts of moderate-intensity walking every 20 min (SIT + MA). A standardised test drink was provided at the start of each trial and an ad libitum pasta test meal provided at the end of each trial. Subjective appetite ratings and plasma acylated ghrelin, peptide YY, insulin, and glucose were measured at regular intervals. Area under the curve (AUC) was calculated for each variable. AUC values for appetite and gut hormone concentrations were unaffected in the activity breaks conditions compared with uninterrupted sitting (linear mixed modelling: p > 0.05). Glucose AUC was lower in SIT + MA than in SIT + LA (p = 0.004) and SIT (p = 0.055). There was no difference in absolute ad libitum energy intake between conditions (p > 0.05); however, relative energy intake was lower in SIT + LA (39%; p = 0.011) and SIT + MA (120%; p < 0.001) than in SIT. In conclusion, breaking up prolonged sitting does not alter appetite and gut hormone responses to a meal over a 5-h period. Increased energy expenditure from activity breaks could promote an energy deficit that is not compensated for in a subsequent meal. PMID- 26872295 TI - Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation. AB - A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 +/- 3.2 years; height, 178.9 +/- 5.5 cm; weight, 78.5 +/- 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENO increased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENO and TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men. PMID- 26872297 TI - Single-syringe ketamine-propofol for induction of anaesthesia in rabbits. AB - OBJECTIVE: To evaluate and compare three intravenous (IV) doses of a ketamine propofol admixture (ketofol) for induction of anaesthesia in unpremedicated rabbits. STUDY DESIGN: Prospective, randomized 'blinded' trial. ANIMALS: Twenty one healthy female New Zealand rabbits weighing 2.7 +/- 0.1 kg. METHODS: Animals were allocated randomly into three groups of seven animals and received 1 (KP1), 3 (KP3) or 5 (KP5) mg kg(-1) of both ketamine and propofol in a 1:1 mg kg(-1) ratio admixture. Cardiorespiratory parameters and arterial blood gases were measured at baseline, 2 and 5 minutes after drug administration. The time to loss of the righting reflex (LORR) and the duration of action and apnoea were recorded. The quality of induction and intubation were scored. Data were compared using a two-way anova or a t-test for unpaired data, as relevant. RESULTS: The time to LORR was the shortest (11 +/- 5 seconds) and the duration of action the longest (374 +/- 26 seconds) in group KP5. Group KP1 did not lose the righting reflex; instead mild to moderate sedation was observed in this group. The quality of induction in group KP5 was smooth, but ranged from smooth to fair in group KP3. Intubation was not possible in the KP1 group, and 10 animals in the other two groups showed some resistance to intubation. At 2 and 5 minutes, the pulse rate was significantly higher in all three groups compared with baseline, but no statistical differences were seen in arterial blood pressures. Hypoxaemia and dose-dependent respiratory depression were observed in all groups, with periods of apnoea in the KP5 group. CONCLUSIONS AND CLINICAL RELEVANCE: The IV ketamine propofol admixture had a dose-dependent effect. Haemodynamic function was well maintained in all groups but hypoxemia was observed at the highest doses and oxygen administration is recommended. Addition of premedication or topical lidocaine is advisable to make intubation easier. PMID- 26872298 TI - Reproduction in the extremes: That is one tough nut ...errhh...drupe to crack! PMID- 26872299 TI - Thermodynamics for the Formation of Double-Stranded DNA-Single-Walled Carbon Nanotube Hybrids. AB - For the first time, the thermodynamics are described for the formation of double stranded DNA (ds-DNA)-single-walled carbon nanotube (SWNT) hybrids. This treatment is applied to the exchange reaction of sodium cholate (SC) molecules on SWNTs and the ds-DNAs d(A)20 -d(T)20 and nuclear factor (NF)-kappaB decoy. UV/Vis/near-IR spectroscopy with temperature variations was used for analyzing the exchange reaction on the SWNTs with four different chiralities: (n,m)=(8,3), (6,5), (7,5), and (8,6). Single-stranded DNAs (ss-DNAs), including d(A)20 and d(T)20, are also used for comparison. The d(A)20-d(T)20 shows a drastic change in its thermodynamic parameters around the melting temperature (Tm ) of the DNA oligomer. No such Tm dependency was measured, owing to high Tm in the NF-kappaB decoy DNA and no Tm in the ss-DNA. PMID- 26872301 TI - Subjective judgments in the nuclear energy debate. PMID- 26872300 TI - Extranodal NK/T-cell lymphoma, nasal type of the uterine cervix: A case report. AB - We report a rare case of extranodal NK/T-cell lymphoma, nasal type of the uterine cervix that showed cytologic features mimicking cervical cancer. A 65-year-old woman presented with vaginal bleeding. Gynecological examination revealed a bulky tumor of the cervix. A conventional Papanicolaou-stained cervical smear showed hypercellularity consisting of numerous variably sized cohesive clusters that mimicked epithelial tumors, with a necrotic and inflammatory background. A small number of individually scattered cells were also identified. These scattered cells showed pleomorphic, often cleaved, or horseshoe-shaped nuclei and pale cytoplasm. Biopsy specimens revealed a diffuse growth of atypical cells with an angiocentric pattern. Extensive necrosis and infiltration of inflammatory cells were present. There were numerous mitotic figures. The tumor cells were positive for CD45RO, CD3epsilon, CD56, granzyme B, TIA-1, CD7, and Epstein-Barr virus (EBV)-encoded small RNA (EBER) by in situ hybridization, and negative for cytokeratin, chromogranin A, synaptophysin, CD4, CD5, CD8, CD20, and CD30. Based on these findings, this tumor was diagnosed as extranodal NK/T-cell lymphoma, nasal type of the uterine cervix. PMID- 26872302 TI - Randomized trial of a physical activity intervention in women with metastatic breast cancer. AB - BACKGROUND: Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer. METHODS: Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire. RESULTS: A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants. CONCLUSIONS: Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment. PMID- 26872303 TI - Male long-tailed macaques (Macaca fascicularis) understand the target of facial threat. AB - The cognitive demands of group living have resulted in the development of social competences in a wide range of animal species. Primates are well aware of the complex social structure within their group and infer information about social status by observing interactions of others. A capacity used to infer this information, Visual Perspective Taking (VPT), is present in apes and in monkeys. However, it is unclear whether monkeys really understand that another individual is looking at a specific target. We investigated whether monkeys understand the target of attention of conspecifics using a new paradigm, based on expectancy violation. Subjects were exposed to pictures of scenes involving group members. These pictures either represented congruent (agonistic signals consistent with the dominance hierarchy) or incongruent (signals contradict the dominance hierarchy) social situations. The only difference between scenes concerned the looking direction, that is, the target of attention, and facial expression of the central monkey in the picture. Female subjects did not differ in their looking times to incongruent and congruent scenes, but results may be confounded by their longer looking times at scenes involving kin than non-kin. Male subjects looked significantly longer at incongruent than congruent scenes, suggesting that they understand the target of attention of other individuals. Alternative explanations involving simpler cognitive capacities were excluded. This implies that monkey species share social cognitive capacities underlying VPT with apes and humans. Am. J. Primatol. 78:720-730, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26872304 TI - Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression. AB - Apigenin (4',5,7-trihydroxyflavone), a flavonoid commonly found in fruits and vegetables, has anticancer properties in various malignant cancer cells. However, the molecular basis of the anticancer effect remains to be elucidated. In this study, we investigated the cellular mechanisms underlying the induction of cell cycle arrest by apigenin. Our results showed that apigenin at the nonapoptotic induction concentration inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in the MDA-MB-231 breast cancer cell line. Immunoblot analysis indicated that apigenin suppressed the expression of cyclin A, cyclin B, and cyclin-dependent kinase-1 (CDK1), which control the G2-to-M phase transition in the cell cycle. In addition, apigenin upregulated p21WAF1/CIP1 and increased the interaction of p21WAF1/CIP1 with proliferating cell nuclear antigen (PCNA), which inhibits cell cycle progression. Furthermore, apigenin significantly inhibited histone deacetylase (HDAC) activity and induced histone H3 acetylation. The subsequent chromatin immunoprecipitation (ChIP) assay indicated that apigenin increased acetylation of histone H3 in the p21WAF1/CIP1 promoter region, resulting in the increase of p21WAF1/CIP1 transcription. In a tumor xenograft model, apigenin effectively delayed tumor growth. In these apigenin-treated tumors, we also observed reductions in the levels of cyclin A and cyclin B and increases in the levels of p21WAF1/CIP1 and acetylated histone H3. These findings demonstrate for the first time that apigenin can be used in breast cancer prevention and treatment through epigenetic regulation. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 434-444, 2017. PMID- 26872306 TI - Unilateral prurigo pigmentosa: A report of two cases. PMID- 26872305 TI - Benchmarking novel approaches for modelling species range dynamics. AB - Increasing biodiversity loss due to climate change is one of the most vital challenges of the 21st century. To anticipate and mitigate biodiversity loss, models are needed that reliably project species' range dynamics and extinction risks. Recently, several new approaches to model range dynamics have been developed to supplement correlative species distribution models (SDMs), but applications clearly lag behind model development. Indeed, no comparative analysis has been performed to evaluate their performance. Here, we build on process-based, simulated data for benchmarking five range (dynamic) models of varying complexity including classical SDMs, SDMs coupled with simple dispersal or more complex population dynamic models (SDM hybrids), and a hierarchical Bayesian process-based dynamic range model (DRM). We specifically test the effects of demographic and community processes on model predictive performance. Under current climate, DRMs performed best, although only marginally. Under climate change, predictive performance varied considerably, with no clear winners. Yet, all range dynamic models improved predictions under climate change substantially compared to purely correlative SDMs, and the population dynamic models also predicted reasonable extinction risks for most scenarios. When benchmarking data were simulated with more complex demographic and community processes, simple SDM hybrids including only dispersal often proved most reliable. Finally, we found that structural decisions during model building can have great impact on model accuracy, but prior system knowledge on important processes can reduce these uncertainties considerably. Our results reassure the clear merit in using dynamic approaches for modelling species' response to climate change but also emphasize several needs for further model and data improvement. We propose and discuss perspectives for improving range projections through combination of multiple models and for making these approaches operational for large numbers of species. PMID- 26872307 TI - Predictors of 30-Day Hospital Readmission After Posterior Cervical Fusion in 3401 Patients. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of the study was to determine readmission rates and predictors of readmission after posterior cervical fusion (PCF). SUMMARY OF BACKGROUND DATA: PCFs are common spinal operations for a variety of spinal disorders including cervical myelopathy, unstable fractures, cervical deformity, and tumors. Data elaborating on risk factors for 30-day readmission are limited. METHODS: Data were collected from the 2006 to 2013 American College of Surgeons National Surgical Quality Improvement Program database. Predictors of 30-day readmission comprising patient demographics, comorbidities, operative features, and postoperative complications were identified through logistic multivariable regression. RESULTS: A total of 3401 patients met study criteria. Rate of 30-day readmission was 6.20%. Multilevel fusion was performed in 69.16% of patients. Postoperative infection was the most reason, accounting for 17.06% of all readmissions. Age older than 70 years (odds ratio [OR] = 1.61, P = 0.012), renal failure requiring dialysis (OR = 3.69, P = 0.011), anemia (OR = 1.57, P = 0.006), multilevel fusion (OR = 1.61, P = 0.012), surgical site infections (OR = 20.4, P < 0.001), wound dehiscence (OR = 19.08, P < 0.001), postoperative pneumonia (OR = 2.75, P = 0.01), pulmonary embolism (OR = 15.39, P < 0.001), and progressing renal insufficiency (OR = 10.13, P = 0.061) were significant predictors of hospital readmission. CONCLUSION: The identified predictors of readmission after PCF can improve patient counseling, identification of high-risk patients, and guide changes in healthcare delivery pathways. Patients with modifiable risk factors such as anemia and kidney failure may benefit from preoperative optimization. In addition, postoperative complications represent a key target for intervention. LEVEL OF EVIDENCE: 3. PMID- 26872308 TI - Acquired resistance to HSP90 inhibitor 17-AAG and increased metastatic potential are associated with MUC1 expression in colon carcinoma cells. AB - Heat shock protein 90 (HSP90) is a molecular chaperone required for the stability and function of many proteins. The chaperoning of oncoproteins by HSP90 enhances the survival, growth, and invasive potential of cancer cells. HSP90 inhibitors are promising new anticancer agents, in which the benzoquinone ansamycin 17 allylamino-17-demethoxygeldanamycin (17-AAG) is currently in clinical evaluation. However, the implications of acquired resistance to this class of drug remain largely unexplored. In the present study, we have generated isogenic human colon cancer cell lines that are resistant to 17-AAG by continued culturing in the compound. Cross-resistance was found with another HSP90 inhibitor 17 dimethylaminoethylamino-17-demethoxygeldanamycin. The resistant cells showed obvious morphology changes with a metastatic phenotype and significant increases in migration and adhesion to collagens. Western blotting analysis of epithelial mesenchymal transition molecular markers found that expression of E-cadherin downregulated, whereas expression of N-cadherin and beta-catenin upregulated in the resistant cells. Mucin 1 (MUC1) has been reported to mediate metastasis as well as chemical resistance in many cancers. Here, we found that MUC1 expression was significantly elevated in the acquired drug resistance cells. 17-AAG treatment could decrease MUC1 more in parental cells than in acquired 17-AAG resistant cells. Further study found that knockdown of MUC1 expression by small interfering RNA could obviously re-sensitize the resistant cells to 17-AAG treatment, and decrease the cell migration and adhesion. These were coupled with a downregulation in N-cadherin and beta-catenin. The results indicate that HSP90 inhibitor therapies in colon carcinomas could generate resistance and increase metastatic potential that might mediated by upregulation of MUC1 expression. Findings from this study further our understanding of the potential clinical effects of HSP90-directed therapies in colon carcinomas. PMID- 26872309 TI - LJNK, an indoline-2,3-dione-based aminopeptidase N inhibitor with promising antitumor potency. AB - In our previous study, we found that LJNK showed potent aminopeptidase N (APN) inhibitory activity. In the current study, we further evaluated the antitumor effects of LJNK both in vitro and in vivo. Enzyme experiments showed that LJNK showed better inhibitory activity than bestatin against APN both from human carcinoma cells' surface and from porcine kidney microsomes. In addition, LJNK could suppress rat aortic ring microvessel growth and HUVEC tubular structure formation, which showed its stronger antiangiogenesis effects than bestatin. [(3 [4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide)] assay and clonogenic assay showed that LJNK suppressed cancer cell growth both in the short and the long term. Mice bearing H22 transplantation tumor proved its antitumor effects in vivo. Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that LJNK could induce 28.1% PLC/PRF/5 cell apoptosis and the apoptotic pathway was probably identified by western blot. The above-mentioned results suggested that LJNK inhibited cell proliferation and angiogenesis, and induced apoptosis by decreasing APN activity. PMID- 26872310 TI - Liver X receptor as a drug target for the treatment of breast cancer. AB - Liver X receptor (LXR) has been exploited widely as a drug target in breast cancer treatment, and various mechanisms underlying the effects of LXR in this area are well studied. The activated LXR plays important roles in estrogen receptor alpha (ERalpha) breast cancer cells, such as reducing cell proliferation and arresting cell cycle progression. Different LXR ligands have diverse effects on the development of breast cancer, such as the inhibitory effect of oxysterol, which can return cells to normocholesterol conditions and target other metabolic genes. Moreover, 27-hydroxycholesterol, a locally produced cholesterol metabolite, reportedly promotes the proliferation of ERalpha breast cancer cells in vitro and facilitates tumor metastasis with other LXR ligands. Moreover, the expression of LXR also exerts potential effects on immune surveillance, tumor immunity, and tumor microenvironment. These advances in breast cancer research indicate that LXR may be a new therapeutic target to treat the refractory or drug resistant subtypes of breast cancer. PMID- 26872311 TI - Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis. AB - The aim of this study was to compare the efficacies between adoptive immunotherapy combined chemoradiotherapy and chemoradiotherapy alone in patients with non-small-cell lung cancer (NSCLC). The databases PubMed, EMBASE, and Cochrane database were searched to identify eligible clinical trials. Data analyses were carried out using a comprehensive meta-analysis program, version 2 software. A total of seven articles were finally included in the analysis. Meta analyses showed that compared with chemoradiotherapy alone, adoptive immunotherapy combined with chemoradiotherapy could improve the 2-year overall survival [odds ratio (OR)=2.45, 95% confidence interval (CI): 1.60-3.75, P<0.001], but not 2-year progression-free survival (OR=1.81, 95% CI: 0.61-5.36, P=0.284). Specifically, early (OR=3.32, 95% CI: 1.38-7.95, P<0.01) but not advanced (OR=3.75, 95% CI: 0.96-14.68, P=0.057) NSCLC patients were likely to gain a large benefit from the adoptive immunotherapy. Most of the adoptive immunotherapy-induced adverse effects were self-limited, mainly including fever, shiver, nausea, fatigue, etc. and severe toxicities were not observed. Adoptive immunotherapy combined with chemoradiotherapy can delay the recurrence of NSCLC and improve survival in patients, where the benefits are even more significant in patients with early-stage NSCLC. PMID- 26872312 TI - Role of reverse transendothelial migration of neutrophils in inflammation. AB - Transmigration of neutrophils through vascular endothelial walls into the inflamed tissues is a critical defense mechanism of innate immune system against infection and injury caused by sepsis, trauma, ischemia-reperfusion, and other acute or chronic inflammatory diseases. However, their excessive infiltration and uncontrolled activation may lead to the destruction of normal tissue architecture and unrestrained inflammation. Transendothelial migration (TEM) in a luminal-to abluminal direction is widely known as the final step of neutrophil migration cascade into the inflamed tissues. Recent studies have shown that neutrophils not necessarily move from the vascular lumen to the extravascular tissues in a one way direction; they also proceed in an opposite direction, known as reverse transendothelial migration (rTEM) to get back into the vascular lumen again. This novel paradigm of neutrophil round trip is currently on the spotlight due to its possible interaction with immune system. Current review highlighting the growing demand of this newly identified neutrophil migratory event will not only rewrite the disease pathophysiology, but also help scientists design novel therapeutic strategy leading to the remission of inflammatory diseases in which controlling exaggerated neutrophil infiltration is a major challenge. PMID- 26872313 TI - Coordination of stress, Ca2+, and immunogenic signaling pathways by PERK at the endoplasmic reticulum. AB - The endoplasmic reticulum (ER) is the main coordinator of intracellular Ca2+ signaling, protein synthesis, and folding. The ER is also implicated in the formation of contact sites with other organelles and structures, including mitochondria, plasma membrane (PM), and endosomes, thereby orchestrating through interorganelle signaling pathways, a variety of cellular responses including Ca2+ homeostasis, metabolism, and cell death signaling. Upon loss of its folding capacity, incited by a number of stress signals including those elicited by various anticancer therapies, the unfolded protein response (UPR) is launched to restore ER homeostasis. The ER stress sensor protein kinase RNA-like ER kinase (PERK) is a key mediator of the UPR and its role during ER stress has been largely recognized. However, growing evidence suggests that PERK may govern signaling pathways through UPR-independent functions. Here, we discuss emerging noncanonical roles of PERK with particular relevance for the induction of danger or immunogenic signaling and interorganelle communication. PMID- 26872314 TI - Sex steroid hormone stability in serum tubes with and without separator gels. AB - BACKGROUND: A pilot study showing a decrease in androstenedione concentration in serum collected into gel-containing serum tubes (STs) triggered an investigation of the effect of serum collection tube on steroid hormone stability. METHODS: In the main study, two tube types were examined: BD Vacutainer(r) SSTTMII Advance and BD Vacutainer(r) Serum Tube. Forty-seven serum samples from apparently healthy volunteers were collected and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for testosterone, androstenedione, 17 hydroxyprogesterone (17-OHP) (n=20); and oestradiol (n=27). Primary specimens were centrifuged once, maintained at room temperature and extracted within 2 h for day zero (d0) results. To assess stability following refrigeration (2-8 degrees C), aliquots were taken from the primary tube on day one (d1) and day five (d5) and analysed immediately. Differences in measurand concentration between tubes at d0 and following storage (d1 and d5) were evaluated for statistical significance. RESULTS: There was a progressive and statistically significant decrease in androstenedione concentration from d0 to d5 (p<0.001) in the SSTTMII tubes. In addition, there was a statistically significant reduction in testosterone, 17-OHP and oestradiol concentrations at d5 (p<0.01). Interestingly, oestradiol and testosterone concentrations increased with time in plain STs (p<0.01). The only change likely to have a clinical impact was that of androstenedione in serum gel tubes. CONCLUSIONS: To optimise conditions and to reduce pre-analytical error we recommend the use of plain serum collection tubes for androstenedione and rapid separation of serum from cells when oestradiol and testosterone are requested. PMID- 26872315 TI - Effective quality management practices in routine clinical next-generation sequencing. AB - BACKGROUND: Molecular technologies have allowed laboratories to detect and establish the profiles of human cancers by identifying a variety of somatic variants. In order to improve personalized patient care, we have established a next-generation sequencing (NGS) test to screen for somatic variants in primary or advanced cancers. In this study, we describe the laboratory quality management program for NGS testing, and also provide an overview of the somatic variants identified in over 1000 patient samples as well as their implications in clinical practice. METHODS: Over the past one-and-a-half years, our laboratory received a total of 1028 formalin-fixed, paraffin-embedded (FFPE) tumor tissues, which consisted of non-small-cell lung carcinomas (NSCLCs), colon adenocarcinomas, glioma/glioblastomas, melanomas, breast carcinomas, and other tumor types. During this time period, we implemented a series of quality control (QC) checks that included (1) pre-DNA extraction, (2) DNA quantification, (3) DNA quality, (4) library quantification, (5) post-emulsification PCR, and (6) post-sequencing metrics. At least 10 ng of genomic DNA (gDNA) were used to prepare barcoded libraries using the AmpliSeq CHPv2. Samples were multiplexed and sequenced on Ion Torrent 318 chips using the Ion PGM System. Variants were identified using the Variant Caller Plugin, and annotation and functional predictions were performed using the Golden Helix SVS. RESULTS: A total of 1005 samples passed QC1-3, and following additional library preparation QC checkpoints, 877 samples were sequenced. Samples were classified into two categories: wild-type (127) and positive for somatic variants (750). Somatic variants were classified into clinically actionable (60%) and non-actionable (40%). CONCLUSIONS: The use of NGS in routine clinical laboratory practice allowed for the detection of tumor profiles that are essential for the selection of targeted therapies and identification of applicable clinical trials, contributing to the improvement of personalized patient care in oncology. PMID- 26872317 TI - The moderate essential amino acid restriction entailed by low-protein vegan diets may promote vascular health by stimulating FGF21 secretion. AB - The serum total and LDL cholesterol levels of long-term vegans tend to be very low. The characteristically low ratio of saturated to unsaturated fat in vegan diets, and the absence of cholesterol in such diets, clearly contribute to this effect. But there is reason to suspect that the quantity and composition of dietary protein also play a role in this regard. Vegan diets of moderate protein intake tend to be relatively low in certain essential amino acids, and as a result may increase hepatic activity of the kinase GCN2, which functions as a gauge of amino acid status. GCN2 activation boosts the liver's production of fibroblast growth factor 21 (FGF21), a factor which favorably affects serum lipids and metabolic syndrome. The ability of FGF21 to decrease LDL cholesterol has now been traced to at least two mechanisms: a suppression of hepatocyte expression of sterol response element-binding protein-2 (SREBP-2), which in turn leads to a reduction in cholesterol synthesis; and up-regulated expression of hepatocyte LDL receptors, reflecting inhibition of a mechanism that promotes proteasomal degradation of these receptors. In mice, the vascular benefits of FGF21 are also mediated by favorable effects on adipocyte function - most notably, increased adipocyte secretion of adiponectin, which directly exerts anti inflammatory effects on the vasculature which complement the concurrent reduction in LDL particles in preventing or reversing atherosclerosis. If, as has been proposed, plant proteins preferentially stimulate glucagon secretion owing to their amino acid composition, this would represent an additional mechanism whereby plant protein promotes FGF21 activity, as glucagon acts on the liver to boost transcription of the FGF21 gene. PMID- 26872316 TI - Thirty-minutes' exposure to smartphone call triggers neutrophil activation in vitro. AB - BACKGROUND: Despite accumulating evidence about the negative health effects of exposure to electromagnetic fields emitted by mobile phones, no information is available on the potential impact of radiofrequency (RF) waves on polymorphonuclear leukocytes biology. METHODS: Two sequential whole blood tubes were collected from 16 ostensibly healthy volunteers. After placing the former tube of each subject in a plastic rack, 1 cm from a commercial smartphone (carrier frequency, 900 MHz), a call was placed on the smartphone and a communication lasting 30 min was manually activated. The latter blood tube of each volunteer was placed in another plastic rack, for an identical period of time, avoiding close contact with sources of RF waves. A complete blood count was then assessed in all whole blood samples, using Advia 2120. RESULTS: The 30-min exposure of blood to RF waves did not induce significant variations of total and differential leukocyte counts. A significant decrease was however observed for many neutrophils parameters, with median percentage variation of -3.9% for the lobularity index (LI), -29.8% for the myeloperoxidase index (MPXI), -0.6% for the neutrophil cluster mean x (NEUTx) and -0.7% for the neutrophil cluster mean y (NEUTy), respectively. The percentage of blood samples with reduced values after exposure to RF waves was 81% for LI, 88% for NEUTx and 100% for both MPXI and NEUTy. CONCLUSIONS: The results of this study show that exposure to smartphone RF waves triggers activation of neutrophils in vitro, as mirrored by the significant variations observed in many activation parameters in Advia 2120. PMID- 26872318 TI - Neonatal exposure to estradiol-17beta modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats. AB - The sexually dimorphic organization in perinatal rat brain is influenced by steroid hormones. Exposure to high levels of estrogen or endocrine-disrupting compounds during perinatal period may perturb this process, resulting in compromised reproductive physiology and behavior as observed in adult In our recent observation neonatal exposure of the female rats to estradiol-17beta resulted in down-regulation of TNF-alpha, up-regulation of COX-2 and increase in SDN-POA size in pre-optic area in the adulthood. It is known that the control of reproductive performance in female involves a complex interplay of the hypothalamus, pituitary, and ovary. The present study was undertaken to understand the possible molecular mechanism involved in changes observed in the ovarian morphology and expression of selected genes in the ovary. Administration of estradiol-17beta (100 MUg) on day 2 and 3 after birth revealed up-regulation of ER-alpha, ER-beta, COX-2 and down-regulation of TNF-alpha expression. Also the decrease in the ovarian weight, altered ovarian morphology and changes in the 2D protein profiles were also seen. This is apparently the first report documenting that neonatal estradiol exposure modulates TNF-alpha and COX-2 expression in the ovary as seen during adult stage. Our results permit us to suggest that cues originating from the modified brain structure due to neonatal exposure of estradiol-17beta remodel the ovary at the molecular level in such a way that there is a disharmony in the reproductive function during adulthood and these changes are perennial and can lead to infertility and changes of reproductive behavior. PMID- 26872319 TI - Blood glucose screening among elderly Malaysians: Who to target? AB - BACKGROUND: Early detection of raised blood glucose can reduce the risk of developing diabetes. Despite being a high-risk group, a significant proportion of the elderly population does not undergo blood glucose screening. The aim of the present study was to examine the factors affecting blood glucose screening among the elderly. METHODS: Data from a sample of 2463 respondents in the National Health and Morbidity Survey 2011 were used. Pearson Chi-squared tests were conducted to find factors associated with screening behavior. A logit model was used to analyze the likelihood of screening. RESULTS: Income, age, education, ethnicity, employment status, availability of medical coverage, and smoking behavior were significantly associated with blood glucose screening. The likelihood of blood glucose screening was positively correlated with available monthly income and was higher in those aged 60-69 years, those attaining higher education, Malays, and elderly who are medically covered. CONCLUSIONS: The findings of the present study provide insights for health policy formulation for the elderly. As part of their efforts to reduce national health costs, governments should pay particular attention to the elderly, who are likely to be unscreened for blood glucose levels, because they face even larger risk exposure. PMID- 26872320 TI - Prediction of the Passive Intestinal Absorption of Medicinal Plant Extract Constituents with the Parallel Artificial Membrane Permeability Assay (PAMPA). AB - At the early drug discovery stage, the high-throughput parallel artificial membrane permeability assay is one of the most frequently used in vitro models to predict transcellular passive absorption. While thousands of new chemical entities have been screened with the parallel artificial membrane permeability assay, in general, permeation properties of natural products have been scarcely evaluated. In this study, the parallel artificial membrane permeability assay through a hexadecane membrane was used to predict the passive intestinal absorption of a representative set of frequently occurring natural products. Since natural products are usually ingested for medicinal use as components of complex extracts in traditional herbal preparations or as phytopharmaceuticals, the applicability of such an assay to study the constituents directly in medicinal crude plant extracts was further investigated. Three representative crude plant extracts with different natural product compositions were chosen for this study. The first extract was composed of furanocoumarins (Angelica archangelica), the second extract included alkaloids (Waltheria indica), and the third extract contained flavonoid glycosides (Pueraria montana var. lobata). For each medicinal plant, the effective passive permeability values Pe (cm/s) of the main natural products of interest were rapidly calculated thanks to a generic ultrahigh-pressure liquid chromatography-UV detection method and because Pe calculations do not require knowing precisely the concentration of each natural product within the extracts. The original parallel artificial membrane permeability assay through a hexadecane membrane was found to keep its predictive power when applied to constituents directly in crude plant extracts provided that higher quantities of the extract were initially loaded in the assay in order to ensure suitable detection of the individual constituents of the extracts. Such an approach is thus valuable for the high-throughput, cost-effective, and early evaluation of passive intestinal absorption of active principles in medicinal plants. In phytochemical studies, obtaining effective passive permeability values of pharmacologically active natural products is important to predict if natural products showing interesting activities in vitro may have a chance to reach their target in vivo. PMID- 26872322 TI - Polycyclic Spiro Lignans and Biphenyl Tetrahydrofuranone Lignans from Gymnotheca involucrata. AB - Four rare polycyclic spiro lignans (1-4) and four new biphenyl tetrahydrofuranone lignans (5-8) were isolated from the whole plant of Gymnotheca involucrata. The structures of the new compounds were elucidated on the basis of detailed spectroscopic analysis and the absolute configuration of 1 was confirmed by single crystal X-ray diffraction. Bioassay results showed that compounds 2 and 6 exhibited weak antifungal activity against Uromyces viciae-fabae at 100 ppm in leaf-disc assays, while compound 3 demonstrated moderate insecticidal activity against Diabrotica balteata at 500 ppm in an artificial diet assay. PMID- 26872321 TI - Sesquiterpenoids with PTP1B Inhibitory Activity and Cytotoxicity from the Edible Mushroom Pleurotus citrinopileatus. AB - One new perhydrobenzannulated 5,5-spiroketal sesquiterpene, pleurospiroketal F (1), as well as six new modified bisabolene sesquiterpenes pleurotins A-F (2-7) were isolated from solid-state fermentation of Pleurotus citrinopileatus. The structures of compounds 1-7 were determined by NMR and MS spectroscopic analysis. The absolute configuration of 1 was determined by X-ray diffraction analysis, while the absolute configurations of 3-7 were assigned using the in situ dimolybdenum circular dichroism method and circular dichroism data comparison. Protein tyrosine phosphatase 1B plays a crucial role as a negative regulator of the insulin-dependent signal cascades. Therefore, the protein tyrosine phosphatase 1B inhibitor can be used for treating type 2 diabetes mellitus and obesity. Compounds 2 and 6 showed moderate inhibitory effects on protein tyrosine phosphatase 1B with IC50 s of 32.1 uM and 30.5 uM, respectively. The kinetic study confirmed compound 2 to be a noncompetitive inhibitor. Compounds 1-7 did not show cytotoxic activity against cancer cell lines (IC50 > 50 uM). PMID- 26872323 TI - Noninvasive ventilation for neuromuscular respiratory failure: when to use and when to avoid. AB - PURPOSE OF REVIEW: Neuromuscular respiratory failure can occur from a variety of diseases, both acute and chronic with acute exacerbation. There is often a misunderstanding about how the nature of the neuromuscular disease should affect the decision on how to ventilate the patient. This review provides an update on the value and relative contraindications for the use of noninvasive ventilation in patients with various causes of primary neuromuscular respiratory failure. RECENT FINDINGS: Myasthenic crisis represents the paradigmatic example of the neuromuscular condition that can be best treated with noninvasive ventilation. Timely use of noninvasive ventilation can substantially reduce the duration of ventilatory assistance in these patients. Noninvasive ventilation can also be very helpful after extubation in patients recovering from an acute cause of neuromuscular respiratory failure who have persistent weakness. Noninvasive ventilation can improve quality of survival in patients with advanced motor neuron disorder (such as amyotrophic lateral sclerosis) and muscular dystrophies, and can avoid intubation when these patients present to the hospital with acute respiratory failure. Attempting noninvasive ventilation is not only typically unsuccessful in patients with Guillain-Barre syndrome, but can also be dangerous in these cases. SUMMARY: Noninvasive ventilation can be very effective to treat acute respiratory failure caused by myasthenia gravis and to prevent reintubation in other neuromuscular patients, but should be used cautiously for other indications, particularly Guillain-Barre syndrome. PMID- 26872325 TI - A prospective study to assess the diagnostic performance of the Sofia((r)) Immunoassay for Influenza and RSV detection. AB - BACKGROUND: Respiratory viruses RSV and influenza A and B viruses are responsible for important disease outbreaks during the winter season in temperate climate regions. Rapid diagnostic tests (RDTs) are assays designed to yield a rapid diagnosis, which facilitates patient management. The Sofia Influenza A+B Fluorescence Immunoassay and Sofia RSV Fluorescence Immunoassay are RDTs for Influenza and RSV detection that employ a new technology to enhance their sensitivity. OBJECTIVES: Sensitivity, specificity and positive and negative predictive values of the assays were calculated compared with the reference diagnostic method: real-time RT-PCR. STUDY DESIGN: A prospective evaluation was carried out on 1065 respiratory samples for Sofia Influenza A+B FIA and on 261 samples for Sofia RSV FIA from November 2013 to April 2014. RESULTS: The sensitivities of the Sofia Influenza A+B FIA for influenza A and influenza B detection were, respectively, 75.3% (244/324) and 50.0% (8/16). The sensitivity of the Sofia RSV FIA was 92.1% (128/139). There were no differences in Sofia FIA performance depending on the virus subtype. CONCLUSIONS: The results showed high sensitivity and specificity values for influenza A and RSV detection, but values were lower for influenza B. More information is needed regarding the performance for influenza B given the small number of positive samples assessed. PMID- 26872324 TI - Development of a Novel Thyroid Function Fluctuated Animal Model for Thyroid Associated Ophthalmopathy. AB - BACKGROUND: The establishment of a suitable and stable animal model is critical for research on thyroid-associated ophthalmopathy (TAO). In clinical practice, we found that patients treated with I-131 often exhibit TAO; therefore, we aimed to establish a novel thyroid function fluctuated animal model of TAO by simulating the clinical treatment process. METHODS: We treated SD rats with I-131 to damage the thyroid and then used sodium levothyroxine (L-T4) to supplement the thyroid hormone (TH) levels every seven days, leading to a fluctuating level of thyroid hormones that simulated the status of clinical TAO patients. Rats administered normal saline were considered as a control. The weight, intraocular pressure, and serum T3, T4, TSH and TRAb levels of the rats were measured, and the pathological changes were analyzed by H&E staining and transmission electron microscopy (TEM). RESULTS: The experimental rats (TAO group) exhibited significantly reduced weight and elevated intraocular pressure compared with the control rats. Meanwhile, the serum levels of T3 and T4 were up-regulated in the TAO group, but the TSH level decreased during the 10-week study. Moreover, increased numbers of blood vessels and inflammatory cell infiltrations were observed in the orbital tissues of the TAO rats, while no abnormal changes occurred in the control rats. The orbital myofibrils in the TAO rats appeared fractured and dissolved, with twisted structures. Mitochondrial swelling and vacuoles within the endoplasmic reticulum, swelling nerve fibers, shedding nerve myelin, and macrophages were found in the TAO group. CONCLUSION: Rats treated with I-131 and sodium levothyroxine exhibited characteristics similar to those of TAO patients in the clinic, providing an effective and simple method for the establishment of a stable animal model for research on the pathogenesis and treatment of TAO. PMID- 26872326 TI - Human pegivirus detected in a patient with severe encephalitis using a metagenomic pan-virus array. AB - We have used a metagenomic microarray to detect genomic RNA from human pegivirus in serum and cerebrospinal fluid from a patient suffering from severe encephalitis. No other pathogen was detected. HPgV in cerebrospinal fluid during encephalitis has never been reported before and its prevalence in cerebrospinal fluid needs further investigation. PMID- 26872327 TI - Nanosized yolk-shell Fe3O4@Zr(OH)x spheres for efficient removal of Pb(II) from aqueous solution. AB - In this work, Fe3O4@Zr(OH)x yolk-shell nanospheres (YSNs) were synthesized via a two-step process and further examined as adsorbents for the removal of Pb(II). To understand the hollow structure on the adsorption properties of Pb(II), another adsorbent without hollow cavities, i.e., Fe3O4@SiO2@Zr(OH)x core-shell nanospheres (CSNs), was also prepared for comparison. The adsorption results showed that Fe3O4@Zr(OH)x YSNs exhibited 41.6% higher Pb(II) adsorption capacity as compared to that of Fe3O4@SiO2@Zr(OH)x CSNs. The isotherm was well fitted to Langmuir adsorption model with qmax value of 310.8 mg/g after normalized by the weight of Zr in Fe3O4@Zr(OH)x YSNs. Scanning transmission electron microscopy (STEM) mapping results revealed that the existence of cavities between Fe3O4 cores and Zr(OH)x shells is responsible for the improved adsorption performance. XPS analysis indicated the surface hydroxyl groups played a key role in the Pb(II) adsorption. The removal efficiency of Pb(II) was maintained above 90% in five consecutive adsorption-desorption cycles. PMID- 26872328 TI - Photocatalytic degradation of Maxilon C.I. basic dye using CS/CoFe2O4/GONCs as a heterogeneous photo-Fenton catalyst prepared by gamma irradiation. AB - CS/CF/GONCs were synthesized via gamma irradiation cross-linking method with the aid of sonication. The nanocomposites exhibited a photo-Fenton catalytic feature for the degradation of Maxilon C.I. basic dye in aqueous medium using sunlight. The effects of pH, H2O2 concentration, and dosage of the catalyst, on the degradation rates of the dyes were examined. The optimal degradation rate was reached with 10mM H2O2 at pH 9.5. It was verified that the Maxilon C.I. basic dye degradation rate fits a pseudo-first-order kinetics for different initial concentrations of Maxilon C.I. dye. Fourth cyclic tests for Maxilon C.I. degradation showed that the magnetic catalyst was very stable, recoverable, highly active, and easy to separate using an external magnet. Hence, this magnetic catalyst has potential use in organic pollutant removal. PMID- 26872330 TI - Structural insights of nucleosome and the 30-nm chromatin fiber. AB - The eukaryotic genome is hierarchically packaged into chromatin in the nucleus. The organization and dynamics of 30-nm chromatin fibers, which is typically regarded as the secondary structure of chromatin, play a crucial role in regulating DNA accessibility for gene expression. Here we reviewed some recent progresses on the structural studies on nucleosomes, nucleosome-protein complexes, and chromatin fibers, focusing on the structural insights how the chromatin structure is regulated by different epigenetic regulation factors. PMID- 26872329 TI - Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese American Adults: The Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults. METHODS AND FINDINGS: Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. alpha Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake. CONCLUSION: Absence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease. PMID- 26872331 TI - Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens. AB - BACKGROUND AND OBJECTIVE: Significant controversy still exists about ritonavir boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI based regimens. METHODS: This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). RESULTS: A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on treatment analysis) at week 96 were 79.3% (CI95, 76.8-81.8) and 91.5% (CI95, 89.6 93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. CONCLUSION: Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for the administered drug. PMID- 26872332 TI - A literature review and meta-analyses of cannabis use and suicidality. AB - BACKGROUND: We lack a review of the epidemiological literature on cannabis use (acute use and chronic-usual quantity/frequency and heavy use) and suicidality (suicide death, suicide ideation, suicide attempt). METHODS: The English language literature on Medline, PsychInfo, Google Scholar, and public-use databases was searched for original articles, critical review reports, and public use data on cannabis use and suicide for the period ranging from 1990-2015 (February). Odds ratios (OR) from random effects in meta-analyses for any cannabis use and heavy cannabis use were calculated. RESULTS: The acute cannabis-suicidality literature mostly includes descriptive toxicology reports. In terms of death by suicide, the average positive cannabis rate was 9.50% for studies sampling from all suicides, with higher cannabis detection rates amongst suicide decedents by non-overdose methods. We found only 4 studies providing estimates for any chronic cannabis use and death by suicide (OR=2.56 (1.25-5.27)). After deleting duplicates we found 6 studies on any cannabis use and suicide ideation (OR=1.43 (1.13-1.83)), 5 studies on heavy cannabis use and suicide ideation (OR=2.53 (1.00-6.39)), 6 studies on any cannabis use and suicide attempt (OR=2.23 (1.24-4.00)) and 6 studies on heavy cannabis use and suicide attempt (OR=3.20 (1.72-5.94)). CONCLUSIONS: We currently lack evidence that acute cannabis use increases imminent risk for suicidality. The evidence tends to support that chronic cannabis use can predict suicidality, but the lack of homogeneity in the measurement of cannabis exposure and, in some instances, the lack of systematic control for known risk factors tempered this finding. PMID- 26872333 TI - Variability in Regularity: Mining Temporal Mobility Patterns in London, Singapore and Beijing Using Smart-Card Data. AB - To discover regularities in human mobility is of fundamental importance to our understanding of urban dynamics, and essential to city and transport planning, urban management and policymaking. Previous research has revealed universal regularities at mainly aggregated spatio-temporal scales but when we zoom into finer scales, considerable heterogeneity and diversity is observed instead. The fundamental question we address in this paper is at what scales are the regularities we detect stable, explicable, and sustainable. This paper thus proposes a basic measure of variability to assess the stability of such regularities focusing mainly on changes over a range of temporal scales. We demonstrate this by comparing regularities in the urban mobility patterns in three world cities, namely London, Singapore and Beijing using one-week of smart card data. The results show that variations in regularity scale as non-linear functions of the temporal resolution, which we measure over a scale from 1 minute to 24 hours thus reflecting the diurnal cycle of human mobility. A particularly dramatic increase in variability occurs up to the temporal scale of about 15 minutes in all three cities and this implies that limits exist when we look forward or backward with respect to making short-term predictions. The degree of regularity varies in fact from city to city with Beijing and Singapore showing higher regularity in comparison to London across all temporal scales. A detailed discussion is provided, which relates the analysis to various characteristics of the three cities. In summary, this work contributes to a deeper understanding of regularities in patterns of transit use from variations in volumes of travellers entering subway stations, it establishes a generic analytical framework for comparative studies using urban mobility data, and it provides key points for the management of variability by policy-makers intent on for making the travel experience more amenable. PMID- 26872335 TI - Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages. AB - Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFalpha and IFNgamma, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels. PMID- 26872334 TI - Combined Immune Therapy for the Treatment of Visceral Leishmaniasis. AB - Chronic disease caused by infections, cancer or autoimmunity can result in profound immune suppression. Immunoregulatory networks are established to prevent tissue damage caused by inflammation. Although these immune checkpoints preserve tissue function, they allow pathogens and tumors to persist, and even expand. Immune checkpoint blockade has recently been successfully employed to treat cancer. This strategy modulates immunoregulatory mechanisms to allow host immune cells to kill or control tumors. However, the utility of this approach for controlling established infections has not been extensively investigated. Here, we examined the potential of modulating glucocorticoid-induced TNF receptor related protein (GITR) on T cells to improve anti-parasitic immunity in blood and spleen tissue from visceral leishmaniasis (VL) patients infected with Leishmania donovani. We found little effect on parasite growth or parasite-specific IFNgamma production. However, this treatment reversed the improved anti-parasitic immunity achieved by IL-10 signaling blockade. Further investigations using an experimental VL model caused by infection of C57BL/6 mice with L. donovani revealed that this negative effect was prominent in the liver, dependent on parasite burden and associated with an accumulation of Th1 cells expressing high levels of KLRG-1. Nevertheless, combined anti-IL-10 and anti-GITR mAb treatment could improve anti-parasitic immunity when used with sub-optimal doses of anti parasitic drug. However, additional studies with VL patient samples indicated that targeting GITR had no overall benefit over IL-10 signaling blockade alone at improving anti-parasitic immune responses, even with drug treatment cover. These findings identify several important factors that influence the effectiveness of immune modulation, including parasite burden, target tissue and the use of anti parasitic drug. Critically, these results also highlight potential negative effects of combining different immune modulation strategies. PMID- 26872337 TI - Mechanical behavior of bilayered small-diameter nanofibrous structures as biomimetic vascular grafts. AB - To these days, the production of a small diameter vascular graft (<6mm) with an appropriate and permanent response is still challenging. The mismatch in the grafts mechanical properties is one of the principal causes of failure, therefore their complete mechanical characterization is fundamental. In this work the mechanical response of electrospun bilayered small-diameter vascular grafts made of two different bioresorbable synthetic polymers, segmented poly(ester urethane) and poly(L-lactic acid), that mimic the biomechanical characteristics of elastin and collagen is investigated. A J-shaped response when subjected to internal pressure was observed as a cause of the nanofibrous layered structure, and the materials used. Compliance values were in the order of natural coronary arteries and very close to the bypass gold standard-saphenous vein. The suture retention strength and burst pressure values were also in the range of natural vessels. Therefore, the bilayered vascular grafts presented here are very promising for future application as small-diameter vessel replacements. PMID- 26872336 TI - Vitamin D Supplementation Reduces Induction of Epithelial-Mesenchymal Transition in Allergen Sensitized and Challenged Mice. AB - Asthma is a chronic disease of the lung associated with airway hyperresponsiveness (AHR), airway obstruction and airway remodeling. Airway remodeling involves differentiation of airway epithelial cells into myofibroblasts via epithelial-mesenchymal transition (EMT) to intensify the degree of subepithelial fibrosis. EMT involves loss in E-cadherin with an increase in mesenchymal markers, including vimentin and N-cadherin. There is growing evidence that vitamin D has immunomodulatory and anti-inflammatory properties. However, the underlying molecular mechanisms of these effects are still unclear. In this study, we examined the contribution of vitamin D on the AHR, airway inflammation and expression of EMT markers in the airways of mice sensitized and challenged with a combination of clinically relevant allergens, house dust mite, ragweed, and Alternaria (HRA). Female Balb/c mice were fed with vitamin D-sufficient (2000 IU/kg) or vitamin D-supplemented (10,000 IU/kg) diet followed by sensitization with HRA. The density of inflammatory cells in the bronchoalveolar lavage fluid (BALF), lung histology, and expression of EMT markers by immunofluorescence were examined. Vitamin D-supplementation decreased AHR, airway inflammation in the BALF and the features of airway remodeling compared to vitamin D-sufficiency in HRA-sensitized and -challenged mice. This was accompanied with increased expression of E-cadherin and decreased vimentin and N-cadherin expression in the airways. These results indicate that vitamin D may be a beneficial adjunct in the treatment regime in allergic asthma. PMID- 26872338 TI - Exploring the biophysical evidence that mammalian two-pore channels are NAADP activated calcium-permeable channels. AB - Nicotinic acid adenine dinucleotide phosphate (NAADP) potently releases Ca(2+) from acidic intracellular endolysosomal Ca(2+) stores. It is widely accepted that two types of two-pore channels, termed TPC1 and TPC2, are responsible for the NAADP-mediated Ca(2+) release but the underlying mechanisms regulating their gating appear to be different. For example, although both TPC1 and TPC2 are activated by NAADP, TPC1 appears to be additionally regulated by cytosolic Ca(2+) . Ion conduction and permeability also differ markedly. TPC1 and TPC2 are permeable to a range of cations although biophysical experiments suggest that TPC2 is slightly more selective for Ca(2+) over K(+) than TPC1 and hence capable of releasing greater quantities of Ca(2+) from acidic stores. TPC1 is also permeable to H(+) and therefore may play a role in regulating lysosomal and cytosolic pH, possibly creating localised acidic domains. The significantly different gating and ion conducting properties of TPC1 and TPC2 suggest that these two ion channels may play complementary physiological roles as Ca(2+) release channels of the endolysosomal system. PMID- 26872339 TI - Gestation and breastfeeding in schistosomotic mothers differently modulate the immune response of adult offspring to postnatal Schistosoma mansoni infection. AB - Schistosoma mansoni antigens in the early life alter homologous and heterologous immunity during postnatal infections. We evaluate the immunity to parasite antigens and ovalbumin (OA) in adult mice born/suckled by schistosomotic mothers. Newborns were divided into: born (BIM), suckled (SIM) or born/suckled (BSIM) in schistosomotic mothers, and animals from noninfected mothers (control). When adults, the mice were infected and compared the hepatic granuloma size and cellularity. Some animals were OA + adjuvant immunised. We evaluated hypersensitivity reactions (HR), antibodies levels (IgG1/IgG2a) anti-soluble egg antigen and anti-soluble worm antigen preparation, and anti-OA, cytokine production, and CD4+FoxP3+T-cells by splenocytes. Compared to control group, BIM mice showed a greater quantity of granulomas and collagen deposition, whereas SIM and BSIM presented smaller granulomas. BSIM group exhibited the lowest levels of anti-parasite antibodies. For anti-OA immunity, immediate HR was suppressed in all groups, with greater intensity in SIM mice accompanied of the remarkable level of basal CD4+FoxP3+T-cells. BIM and SIM groups produced less interleukin (IL)-4 and interferon (IFN)-g. In BSIM, there was higher production of IL-10 and IFN-g, but lower levels of IL-4 and CD4+FoxP3+T-cells. Thus, pregnancy in schistosomotic mothers intensified hepatic fibrosis, whereas breastfeeding diminished granulomas in descendants. Separately, pregnancy and breastfeeding could suppress heterologous immunity; however, when combined, the responses could be partially restored in infected descendants. PMID- 26872340 TI - Bonafide, type-specific human papillomavirus persistence among HIV-positive pregnant women: predictive value for cytological abnormalities, a longitudinal cohort study. AB - This study investigated the rate of human papillomavirus (HPV) persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample), re-infection (detection of different types of HPV in the 2 samples), and type-specific HPV persistence (the same HPV type found in both samples). An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type specific persistence (30%) or re-infection (20%). A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR) was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43 22.79). Our findings show that bonafide (type-specific) HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting. PMID- 26872341 TI - Vitamin D status in a Brazilian cohort of adolescents and young adults with perinatally acquired human immunodeficiency virus infection. AB - The purpose was to determine the prevalence and related factors of vitamin D (VitD) insufficiency in adolescents and young adults with perinatally acquired human immunodeficiency virus. A cohort of 65 patients (17.6 +/- 2 years) at the Federal University of Rio de Janeiro, Brazil, were examined for pubertal development, nutrition, serum parathormone and serum 25-hydroxyvitamin D [s25(OH)D]. s25(OH)D levels < 30 ng/mL (< 75 nmol/L) were defined as VitD insufficiency. CD4+ T-cell counts and viral load, history of worst clinical status, immunologic status as nadir, current immunologic status, and antiretroviral (ART) regimen were also evaluated as risk factors for VitD insufficiency. Mean s25(OH)D was 37.7 +/- 13.9 ng/mL and 29.2% had VitD insufficiency. There was no difference between VitD status and gender, age, nutritional status, clinical and immunological classification, and type of ART. Only VitD consumption showed tendency of association with s25(OH)D (p = 0.064). Individuals analysed in summer/autumn season had a higher s25(OH)D compared to the ones analysed in winter/spring (42.6 +/- 14.9 vs. 34.0 +/- 11.9, p = 0.011). Although, the frequency of VitD insufficiency did not differ statistically between the groups (summer/autumn 17.9% vs. winter/spring 37.8%, p = 0.102), we suggest to monitor s25(OH)D in seropositive adolescents and young adults, especially during winter/spring months, even in sunny regions. PMID- 26872342 TI - An in-house real-time polymerase chain reaction: standardisation and comparison with the Cobas Amplicor HBV monitor and Cobas AmpliPrep/Cobas TaqMan HBV tests for the quantification of hepatitis B virus DNA. AB - This study aimed to standardise an in-house real-time polymerase chain reaction (rtPCR) to allow quantification of hepatitis B virus (HBV) DNA in serum or plasma samples, and to compare this method with two commercial assays, the Cobas Amplicor HBV monitor and the Cobas AmpliPrep/Cobas TaqMan HBV test. Samples from 397 patients from the state of Sao Paulo were analysed by all three methods. Fifty-two samples were from patients who were human immunodeficiency virus and hepatitis C virus positive, but HBV negative. Genotypes were characterised, and the viral load was measure in each sample. The in-house rtPCR showed an excellent success rate compared with commercial tests; inter-assay and intra-assay coefficients correlated with commercial tests (r = 0.96 and r = 0.913, p < 0.001) and the in-house test showed no genotype-dependent differences in detection and quantification rates. The in-house assay tested in this study could be used for screening and quantifying HBV DNA in order to monitor patients during therapy. PMID- 26872343 TI - Whole genome sequence of Klebsiella pneumoniae U25, a hypermucoviscous, multidrug resistant, biofilm producing isolate from India. AB - Klebsiella pneumoniae U25 is a multidrug resistant strain isolated from a tertiary care hospital in Chennai, India. Here, we report the complete annotated genome sequence of strain U25 obtained using PacBio RSII. This is the first report of the whole genome of K. pneumoniaespecies from Chennai. It consists of a single circular chromosome of size 5,491,870-bp and two plasmids of size 211,813 and 172,619-bp. The genes associated with multidrug resistance were identified. The chromosome of U25 was found to have eight antibiotic resistant genes [blaOXA 1,blaSHV-28, aac(6')1b-cr,catB3, oqxAB, dfrA1]. The plasmid pMGRU25-001 was found to have only one resistant gene (catA1) while plasmid pMGRU25-002 had 20 resistant genes [strAB, aadA1,aac(6')-Ib, aac(3)-IId,sul1,2, blaTEM-1A,1B,blaOXA 9, blaCTX-M-15,blaSHV-11, cmlA1, erm(B),mph(A)]. A mutation in the porin OmpK36 was identified which is likely to be associated with the intermediate resistance to carbapenems in the absence of carbapenemase genes. U25 is one of the few K. pneumoniaestrains to harbour clustered regularly interspaced short palindromic repeats (CRISPR) systems. Two CRISPR arrays corresponding to Cas3 family helicase were identified in the genome. When compared to K. pneumoniaeNTUHK2044, a transposase gene InsH of IS5-13 was found inserted. PMID- 26872344 TI - Adaptive coding of the value of social cues with oxytocin, an fMRI study in autism spectrum disorder. AB - The neuropeptide oxytocin (OT) is one of the major targets of research in neuroscience, with respect to social functioning. Oxytocin promotes social skills and improves the quality of face processing in individuals with social dysfunctions such as autism spectrum disorder (ASD). Although one of OT's key functions is to promote social behavior during dynamic social interactions, the neural correlates of this function remain unknown. Here, we combined acute intranasal OT (IN-OT) administration (24 IU) and fMRI with an interactive ball game and a face-matching task in individuals with ASD (N = 20). We found that IN OT selectively enhanced the brain activity of early visual areas in response to faces as compared to non-social stimuli. OT inhalation modulated the BOLD activity of amygdala and hippocampus in a context-dependent manner. Interestingly, IN-OT intake enhanced the activity of mid-orbitofrontal cortex in response to a fair partner, and insula region in response to an unfair partner. These OT-induced neural responses were accompanied by behavioral improvements in terms of allocating appropriate feelings of trust toward different partners' profiles. Our findings suggest that OT impacts the brain activity of key areas implicated in attention and emotion regulation in an adaptive manner, based on the value of social cues. PMID- 26872345 TI - Cell resistant zwitterionic polyelectrolyte coating promotes bacterial attachment: an adhesion contradiction. AB - Polymers of various architectures with zwitterionic functionality have recently been shown to effectively suppress nonspecific fouling of surfaces by proteins and prokaryotic (bacteria) or eukaryotic (mammalian) cells as well as other microorganisms and environmental contaminants. In this work, zwitterionic copolymers were used to make thin coatings on substrates with the layer-by-layer method. Polyelectrolyte multilayers, PEMUs, were built with [poly(allylamine hydrochloride)], PAH, and copolymers of acrylic acid and either the AEDAPS zwitterionic group 3-[2-(acrylamido)-ethyldimethyl ammonio] propane sulfonate (PAA-co-AEDAPS), or benzophenone (PAABp). Benzophenone allowed the PEMU to be toughened by photocrosslinking post-deposition. The attachment of two mammalian cell lines, rat aortic smooth muscle (A7r5) and mouse fibroblasts (3T3), and the biofilm-forming Gram-negative bacteria Escherichia coli was studied on PEMUs terminated with PAA-co-AEDAPS. Consistent with earlier studies, it is shown that PAH/PAA-co-AEDAPS PEMUs resist the adhesion of mammalian cells, but, contrary to our initial hypothesis, are bacterial adhesive and significantly so after maximizing the surface presentation of PAA-co-AEDAPS. This unexpected contrast in the adhesive behavior of prokaryotic and eukaryotic cells is explained by differences in adhesion mechanisms as well as different responses to the topology and morphology of the multilayer surface. PMID- 26872346 TI - Kidney Function and Cognitive Impairment in People Aged 80 Years and Over with Untreated Hypertension: A Cross-Sectional Survey. AB - BACKGROUND/AIMS: Both kidney dysfunction and cognitive impairment are common problems in hypertensive patients. However, few studies have explored the association between these conditions in hypertensive patients aged 80 or over. The current study was undertaken to determine the impact of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) on cognitive impairment among an 80-year-old population with untreated hypertension in China. METHODS: A total of 395 hypertensive patients aged 80 or over were assessed for the presence of cognitive impairment according to the 30-item Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a score below 24 on MMSE. eGFR was evaluated using the Chinese Modification of Diet in Renal Disease equation. CKD was defined according to categorical approach, which is based on "YES" (eGFR below 60 ml/min) or "NO" (eGFR above 60 ml/min). RESULTS: The mean (SD) age was 83.0 +/- 2.6 years for the sample, of whom 69.8% were female. There were 59 (14.9%) and 280 (71.1%) prevalent cases of CKD and cognitive impairment, respectively. CKD patients were older, had higher scores on Activity of Daily Living (ADL), and lower score on MMSE. After controlling for potential confounding, multiple logistic regressions demonstrated that both CKD and eGFR were associated with cognitive impairment in hypertensive patients aged 80 or over. CONCLUSION: Our study found that both CKD and eGFR were associated with cognitive impairment among hypertensive patients aged 80 or over in China. Therefore, targeted screening for cognitive impairment should be considered in these patients with CKD. PMID- 26872347 TI - Identification of Soil Microbes Capable of Utilizing Cellobiosan. AB - Approximately 100 million tons of anhydrosugars, such as levoglucosan and cellobiosan, are produced through biomass burning every year. These sugars are also produced through fast pyrolysis, the controlled thermal depolymerization of biomass. While the microbial pathways associated with levoglucosan utilization have been characterized, there is little known about cellobiosan utilization. Here we describe the isolation and characterization of six cellobiosan-utilizing microbes from soil samples. Each of these organisms is capable of using both cellobiosan and levoglucosan as sole carbon source, though both minimal and rich media cellobiosan supported significantly higher biomass production than levoglucosan. Ribosomal sequencing was used to identify the closest reported match for these organisms: Sphingobacterium multivorum, Acinetobacter oleivorans JC3-1, Enterobacter sp SJZ-6, and Microbacterium sps FXJ8.207 and 203 and a fungal species Cryptococcus sp. The commercially-acquired Enterobacter cloacae DSM 16657 showed growth on levoglucosan and cellobiosan, supporting our isolate identification. Analysis of an existing database of 16S rRNA amplicons from Iowa soil samples confirmed the representation of our five bacterial isolates and four previously-reported levoglucosan-utilizing bacterial isolates in other soil samples and provided insight into their population distributions. Phylogenetic analysis of the 16S rRNA and 18S rRNA of strains previously reported to utilize levoglucosan and our newfound isolates showed that the organisms isolated in this study are distinct from previously described anhydrosugar-utilizing microbial species. PMID- 26872348 TI - Age- and Sex-Dependency of Laser Speckle Flowgraphy Measurements of Optic Nerve Vessel Microcirculation. AB - PURPOSE: To investigate the relationship between various characteristics of a normal population and laser speckle flowgraphy (LSFG) measurements of mean blur rate (MBR) in the optic nerve head (ONH). METHODS: A total of 189 eyes of 189 normal subjects (93 male, 96 female, mean age 45 +/- 14 years old, age range: 20 72) without any history of hypertension, hyperlipidemia or diabetes were enrolled. ONH microcirculation was measured with LSFG and overall MBR (MA), vessel-area MBR (MV), and tissue-area MBR (MT) were derived from these measurements. The statistical association of these measurements with characteristics such as sex, age, intraocular pressure (IOP) and systolic blood pressure (SBP) was then determined. RESULTS: There was a trend towards decreased IOP and MV and increased SBP with age (P = 0.002, P = 0.035, and P = 0.006, respectively). Furthermore, IOP, MV and SBP were correlated with age (r = -0.23, P = 0.011; r = -0.24, P < 0.001; and r = 0.30, P < 0.001, respectively). Separate multiple regression analyses of independent contributing factors revealed that sex and IOP contributed to MA (P < 0.001 and P = 0.002, respectively), sex, IOP, and age contributed to MV (P < 0.001, P = 0.003, and P = 0.024, respectively), while only IOP contributed to MT (P = 0.003). CONCLUSION: In a normal population, MBR was affected by IOP in both the large vessel and capillary areas of the ONH, but not by SBP. MV was also affected by age and sex, while MT was stable independent of age or sex. PMID- 26872350 TI - Cortical Gyrification Patterns Associated with Trait Anxiety. AB - Dispositional anxiety is a stable personality trait that is a key risk factor for internalizing disorders, and understanding the neural correlates of trait anxiety may help us better understand the development of these disorders. Abnormal cortical folding is thought to reflect differences in cortical connectivity occurring during brain development. Therefore, assessing gyrification may advance understanding of cortical development and organization associated with trait anxiety. Previous literature has revealed structural abnormalities in trait anxiety and related disorders, but no study to our knowledge has examined gyrification in trait anxiety. We utilized a relatively novel measure, the local gyrification index (LGI), to explore differences in gyrification as a function of trait anxiety. We obtained structural MRI scans using a 3T magnetic resonance scanner on 113 young adults. Results indicated a negative correlation between trait anxiety and LGI in the left superior parietal cortex, specifically the precuneus, reflecting less cortical complexity among those high on trait anxiety. Our findings suggest that aberrations in cortical gyrification in a key region of the default mode network is a correlate of trait anxiety and may reflect disrupted local parietal connectivity. PMID- 26872349 TI - Electroencephalographic Fractal Dimension in Healthy Ageing and Alzheimer's Disease. AB - Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging. PMID- 26872351 TI - Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses. AB - Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF) has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM) at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test) and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1), weaning (3WK), adult (10WK) and aged (12-18MO) time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO2 from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (>=10 weeks) should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease. PMID- 26872353 TI - Quality of Health Management Information System for Maternal & Child Health Care in Haryana State, India. AB - BACKGROUND: Despite increasing importance being laid on use of routine data for decision making in India, it has frequently been reported to be riddled with problems. Evidence suggests lack of quality in the health management information system (HMIS), however there is no robust analysis to assess the extent of its inaccuracy. We aim to bridge this gap in evidence by assessing the extent of completeness and quality of HMIS in Haryana state of India. METHODS: Data on utilization of key maternal and child health (MCH) services were collected using a cross-sectional household survey from 4807 women in 209 Sub-Centre (SC) areas across all 21 districts of Haryana state. Information for same services was also recorded from HMIS records maintained by auxiliary nurse midwives (ANMs) at SCs to check under- or over-recording (Level 1 discordance). Data on utilisation of MCH services from SC ANM records, for a subset of the total women covered in the household survey, were also collected and compared with monthly reports submitted by ANMs to assess over-reporting while report preparation (Level 2 discordance) to paint the complete picture for quality and completeness of routine HMIS. RESULTS: Completeness of ANM records for various MCH services ranged from 73% for DPT1 vaccination dates to 94.6% for dates of delivery. Average completeness level for information recorded in HMIS was 88.5%. Extent of Level 1 discordance for iron-folic acid (IFA) supplementation, 3 or more ante-natal care (ANC) visits and 2 Tetanus toxoid (TT) injections was 41%, 16% and 2% respectively. In 48.2% cases, respondents from community as well as HMIS records reported at least one post-natal care (PNC) home visit by ANM. Extent of Level 2 discordance ranged from 1.6% to 6%. These figures were highest for number of women who completed IFA supplementation, contraceptive intra-uterine device insertion and provision of 2nd TT injection during ANC. CONCLUSIONS: HMIS records for MCH services at sub centre level in Haryana state were satisfactory in terms of completeness. However, there were significant differences in terms of reported and evaluated coverage of MCH services. Quality of HMIS needs to be improved in order to make it relevant for public health program planning and research. PMID- 26872352 TI - RecG Directs DNA Synthesis during Double-Strand Break Repair. AB - Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over replication of flanking DNA may occur with deleterious consequences. The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions. However, the primary role of RecG in live cells has remained elusive. Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break. Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks. These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over replication of the terminus region of the chromosome. The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules. This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability. PMID- 26872354 TI - Multiple Mating, Paternity and Complex Fertilisation Patterns in the Chokka Squid Loligo reynaudii. AB - Polyandry is widespread and influences patterns of sexual selection, with implications for sexual conflict over mating. Assessing sperm precedence patterns is a first step towards understanding sperm competition within a female and elucidating the roles of male- and female-controlled factors. In this study behavioural field data and genetic data were combined to investigate polyandry in the chokka squid Loligo reynaudii. Microsatellite DNA-based paternity analysis revealed multiple paternity to be the norm, with 79% of broods sired by at least two males. Genetic data also determined that the male who was guarding the female at the moment of sampling was a sire in 81% of the families tested, highlighting mate guarding as a successful male tactic with postcopulatory benefits linked to sperm deposition site giving privileged access to extruded egg strings. As females lay multiple eggs in capsules (egg strings) wherein their position is not altered during maturation it is possible to describe the spatial / temporal sequence of fertilisation / sperm precedence There were four different patterns of fertilisation found among the tested egg strings: 1) unique sire; 2) dominant sire, with one or more rare sires; 3) randomly mixed paternity (two or more sires); and 4) a distinct switch in paternity occurring along the egg string. The latter pattern cannot be explained by a random use of stored sperm, and suggests postcopulatory female sperm choice. Collectively the data indicate multiple levels of male- and female-controlled influences on sperm precedence, and highlights squid as interesting models to study the interplay between sexual and natural selection. PMID- 26872355 TI - Protein-energy malnutrition is frequent and precocious in children with cri du chat syndrome. AB - Protein-energy malnutrition (PEM) is poorly reported in cri du chat syndrome (CDCS) (OMIM #123450), a genetic disease that causes developmental delay and global growth retardation. The objective was to determine the nutritional status at different ages in children with CDCS and factors associated with PEM. A questionnaire focused on growth and nutritional care was sent to 190 families. Among 36 analyzable questionnaires, growth and nutritional indices compatible with PEM occurred in 47% of patients: 19% before 6 months of age, 24% between 6 12 months and 34% after 12 months. Eight patients received enteral feeding. Speech therapy for swallowing education was performed more often in malnourished children (63% vs. 22%, P < 0.02). PEM is frequent and occurs early in this disease, requiring closed nutritional monitoring. PMID- 26872356 TI - Migration of Ventriculoperitoneal Shunt into a Hernia Sac: An Unusual Complication of Ventriculoperitoneal Shunt Surgery in Children. AB - We report 2 cases of ventriculoperitoneal (VP) shunt migration into an inguinal hernia sac. In both cases hernia manifested itself on the right side in late infancy. We attempted to analyse the anatomical and mechanical factors leading to shunt migration as seen in the X-rays of our cases. PMID- 26872357 TI - Correction: Application and Revision of Montreal Cognitive Assessment in China's Military Retirees with Mild Cognitive Impairment. PMID- 26872359 TI - How Copper Nanowires Grow and How To Control Their Properties. AB - Scalable, solution-phase nanostructure synthesis has the promise to produce a wide variety of nanomaterials with novel properties at a cost that is low enough for these materials to be used to solve problems. For example, solution synthesized metal nanowires are now being used to make low cost, flexible transparent electrodes in touch screens, organic light-emitting diodes (OLEDs), and solar cells. There has been a tremendous increase in the number of solution phase syntheses that enable control over the assembly of atoms into nanowires in the last 15 years, but proposed mechanisms for nanowire formation are usually qualitative, and for many syntheses there is little consensus as to how nanowires form. It is often not clear what species is adding to a nanowire growing in solution or what mechanistic step limits its rate of growth. A deeper understanding of nanowire growth is important for efficiently directing the development of nanowire synthesis toward producing a wide variety of nanostructure morphologies for structure-property studies or producing precisely defined nanostructures for a specific application. This Account reviews our progress over the last five years toward understanding how copper nanowires form in solution, how to direct their growth into nanowires with dimensions ideally suited for use in transparent conducting films, and how to use copper nanowires as a template to grow core-shell nanowires. The key advance enabling a better understanding of copper nanowire growth is the first real-time visualization of nanowire growth in solution, enabling the acquisition of nanowire growth kinetics. By measuring the growth rate of individual nanowires as a function of concentration of the reactants and temperature, we show that a growing copper nanowire can be thought of as a microelectrode that is charged with electrons by hydrazine and grows through the diffusion-limited addition of Cu(OH)2(-). This deeper mechanistic understanding, coupled to an understanding of the structure property relationship of nanowires in transparent conducting films, enabled the production of copper nanowires that can be coated from solution to make films with properties that rival the dominant transparent conductor, indium tin oxide. Finally, we show how copper nanowires can be coated with Zn, Sn, In, Ni, Co, Ag, Au, and Pt to protect them from oxidation or enable their use as transparent electrocatalysts. PMID- 26872358 TI - A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics. AB - The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC's ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC's performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell phone-based fluorescence detector, the TTC will increase the availability of on site molecular diagnostics in low-resource settings. PMID- 26872360 TI - Temporal Gene Expression Analysis and RNA Silencing of Single and Multiple Members of Gene Family in the Lone Star Tick Amblyomma americanum. AB - Saliva is an integral factor in the feeding success of veterinary and medically important ticks. Therefore, the characterization of the proteins present in tick saliva is an important area of tick research. Here, we confirmed previously generated sialotranscriptome data using quantitative real-time PCR. The information obtained in this in-depth study of gene expression was used to measure the effects of metalloprotease gene silencing on tick feeding. We analyzed the temporal expression of seven housekeeping genes and 44 differentially expressed salivary molecules selected from a previously published Amblyomma americanum sialotranscriptome. Separate reference genes were selected for the salivary glands and midgut from among the seven housekeeping genes, to normalize the transcriptional expression of differentially expressed genes. The salivary gland reference gene, ubiquitin, was used to normalize the expression of 44 salivary genes. Unsurprisingly, each gene family was expressed throughout the blood meal, but the expression of specific genes differed at each time point. To further clarify the complex nature of the many proteins found in the saliva, we disrupted the translation of several members of the metalloprotease family. Intriguingly, the nucleotide sequence similarity of the reprolysin metalloprotease gene family is so homologous that a single synthesized dsRNA sequence knocked down multiple members of the family. The use of multigene knockdown yielded a more significant picture of the role of metalloproteases in tick feeding success, and changes were observed in the female engorgement weight and larval hatching success. Interestingly, the depletion of metalloprotease transcripts also reduced the total number of bacteria present in the salivary glands. These data provide insight into the expression and functions of tick salivary proteins expressed while feeding on its host. PMID- 26872361 TI - Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin. AB - Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 MUg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (<= 2 MUg/mL), and the MIC90 for Mannheimia haemolytica (1.0 MUg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (<= 2 MUg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points. PMID- 26872362 TI - Identifying Stable Reference Genes for qRT-PCR Normalisation in Gene Expression Studies of Narrow-Leafed Lupin (Lupinus angustifolius L.). AB - Quantitative Reverse Transcription PCR (qRT-PCR) is currently one of the most popular, high-throughput and sensitive technologies available for quantifying gene expression. Its accurate application depends heavily upon normalisation of gene-of-interest data with reference genes that are uniformly expressed under experimental conditions. The aim of this study was to provide the first validation of reference genes for Lupinus angustifolius (narrow-leafed lupin, a significant grain legume crop) using a selection of seven genes previously trialed as reference genes for the model legume, Medicago truncatula. In a preliminary evaluation, the seven candidate reference genes were assessed on the basis of primer specificity for their respective targeted region, PCR amplification efficiency, and ability to discriminate between cDNA and gDNA. Following this assessment, expression of the three most promising candidates [Ubiquitin C (UBC), Helicase (HEL), and Polypyrimidine tract-binding protein (PTB)] was evaluated using the NormFinder and RefFinder statistical algorithms in two narrow-leafed lupin lines, both with and without vernalisation treatment, and across seven organ types (cotyledons, stem, leaves, shoot apical meristem, flowers, pods and roots) encompassing three developmental stages. UBC was consistently identified as the most stable candidate and has sufficiently uniform expression that it may be used as a sole reference gene under the experimental conditions tested here. However, as organ type and developmental stage were associated with greater variability in relative expression, it is recommended using UBC and HEL as a pair to achieve optimal normalisation. These results highlight the importance of rigorously assessing candidate reference genes for each species across a diverse range of organs and developmental stages. With emerging technologies, such as RNAseq, and the completion of valuable transcriptome data sets, it is possible that other potentially more suitable reference genes will be identified for this species in future. PMID- 26872363 TI - TOPORS, a Dual E3 Ubiquitin and Sumo1 Ligase, Interacts with 26 S Protease Regulatory Subunit 4, Encoded by the PSMC1 Gene. AB - The significance of the ubiquitin-proteasome system (UPS) for protein degradation has been highlighted in the context of neurodegenerative diseases, including retinal dystrophies. TOPORS, a dual E3 ubiquitin and SUMO1 ligase, forms a component of the UPS and selected substrates for its enzymatic activities, such as DJ-1/PARK7 and APOBEC2, are important for neuronal as well as retinal homeostasis, respectively. TOPORS is ubiquitously expressed, yet its mutations are only known to result in autosomal dominant retinitis pigmentosa. We performed a yeast two-hybrid (Y2H) screen of a human retinal cDNA library in order to identify interacting protein partners of TOPORS from the retina, and thus begin delineating the putative disease mechanism(s) associated with the retina-specific phenotype resulting from mutations in TOPORS. The screen led to isolation of the 26 S protease regulatory subunit 4 (P26s4/ PSMC1), an ATPase indispensable for correct functioning of UPS-mediated proteostasis. The interaction between endogenous TOPORS and P26s4 proteins was validated by co-immuno-precipitation from mammalian cell extracts and further characterised by immunofluorescent co localisation studies in cell lines and retinal sections. Findings from hTERT-RPE1 and 661W cells demonstrated that TOPORS and P26s4 co-localise at the centrosome in cultured cells. Immunofluorescent staining of mouse retinae revealed a strong P26s4 reactivity at the interface between retinal pigmented epithelium (RPE) layer and the photoreceptors outer segments (OS). This finding leads us to speculate that P26s4, along with TOPORS, may have a role(s) in RPE phagocytosis, in addition to contributing to the overall photoreceptor and retinal homeostasis via the UPS. PMID- 26872364 TI - Holistic Evaluation of Quality Consistency of Ixeris sonchifolia (Bunge) Hance Injectables by Quantitative Fingerprinting in Combination with Antioxidant Activity and Chemometric Methods. AB - A widely used herbal medicine, Ixeris sonchifolia (Bge.) Hance Injectable (ISHI) was investigated for quality consistency. Characteristic fingerprints of 23 batches of the ISHI samples were generated at five wavelengths and evaluated by the systematic quantitative fingerprint method (SQFM) as well as simultaneous analysis of the content of seven marker compounds. Chemometric methods, i.e., support vector machine (SVM) and principal component analysis (PCA) were performed to assist in fingerprint evaluation of the ISHI samples. Qualitative classification of the ISHI samples by SVM was consistent with PCA, and in agreement with the quantitative evaluation by SQFM. In addition, the antioxidant activities of the ISHI samples were determined by both the off-line and on-line DPPH (2, 2-diphenyl-1-picryldrazyl) radical scavenging assays. A fingerprint efficacy relationship linking the chemical components and in vitro antioxidant activity was established and validated using the partial least squares (PLS) and orthogonal projection to latent structures (OPLS) models; and the online DPPH assay further revealed those components that had position contribution to the total antioxidant activity. Therefore, the combined use of the chemometric methods, quantitative fingerprint evaluation by SQFM, and multiple marker compound analysis in conjunction with the assay of antioxidant activity provides a powerful and holistic approach to evaluate quality consistency of herbal medicines and their preparations. PMID- 26872365 TI - MiR-214 Attenuates Osteogenic Differentiation of Mesenchymal Stem Cells via Targeting FGFR1. AB - BACKGROUND/AIMS: Postmenopausal osteoporosis is closely associated with reduction in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Previous studies have demonstrated that miR-214 plays an important role in the genesis and development of postmenopausal osteoporosis. Here, we performed this study to investigate the potential mechanism by which miR-214 regulates osteoblast differentiation of MSCs. METHODS: First, we explored the expression of miR-214 in MSCs of osteoporotic mice. Next, we examined the change of miR-214 during osteoblast differentiation of MSCs. Then, MSCs were infected with lentiviral vectors expressing miR-214 or miR-214 sponge to investigate the effect of miR-214 on osteoblast differentiation of MSCs. Further, bioinformatics analysis and luciferase reporter assay were performed to identify and validate the target gene of miR-214. RESULTS: MiR-214 was up-regulated in MSCs of osteoporotic mice and down-regulated during osteoblast differentiation of MSCs. Furthermore, overexpression of miR-214 inhibited osteoblast differentiation of MSCs in vitro, whereas inhibition of miR-214 function promoted this process, evidenced by increased expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Bioinformatics, Western blot analysis and luciferase reporter assay demonstrated that FGFR1 is a direct target of miR-214. CONCLUSIONS: MiR-214 attenuates osteogenesis by inhibiting the FGFR1/FGF signaling pathway. Our findings suggest that targeting miR-214 promises to be a potential therapy in treatment of postmenopausal osteoporosis. PMID- 26872366 TI - Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial. AB - BACKGROUND: Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. METHODS: This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and alpha amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. RESULTS: Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. CONCLUSION: For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration. PMID- 26872367 TI - Mechanical Power and Development of Ventilator-induced Lung Injury. AB - BACKGROUND: The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. METHODS: Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. RESULTS: In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r = 0.41, P = 0.001) and lung elastance (r = 0.33, P < 0.01) and decrease in PaO2/FIO2 (r = 0.40, P < 0.001) at the end of the study. CONCLUSION: In piglets, VILI develops if a mechanical power threshold is exceeded. PMID- 26872369 TI - Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway. AB - Tripartite motif-containing 29 (TRIM29) has been reported to be dysregulated in human cancers. Up-regulation of TRIM29 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. However, its expression biological function and clinical significance in nasopharyngeal carcinoma (NPC) remain unclear. In this study, TRIM29 expression was validated by qRT-PCR and immunohistochemistry in 69 NPC samples. Notably, TRIM29 protein expression was significantly and positively correlated with the tumor size, clinical stage and metastasis. TRIM29 was identified as the direct target of miR-335-5p and miR-15b 5p, both of which were down-regulated and negatively associated with TRIM29 expression in NPC cell lines and clinical samples. Ectopic TRIM29 expression promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in NPC cells, while its depletion inhibited cell invasion and EMT phenotype. Mechanistically, TRIM29 overexpression reduced PTEN expression and increase phosphorylated protein level of AKT, p70S6K and 4E-BP1. Correspondingly, AKT inhibitor and Rapamycin blocked the effect of TRIM29 on cell invasion. In conclusion, our results suggest that miR-335-5p and miR-15b-5p down-regulation results in TRIM29 over-expression, which induces proliferation, EMT and metastasis of NPC through the PTEN/AKT/mTOR signaling pathway. PMID- 26872370 TI - Single nucleotide polymorphism in the microRNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes. AB - Hypoxia-inducible factor-1 alpha (HIF-1alpha) is over-expressed in many cancers including pancreatic ductal adenocarcinoma (PDAC) and correlated with poor prognosis. We aim to determine the effect of germline genetic variants on the regulation of the homeostasis of the miRNA-gene regulatory loop in HIF1A gene and PDAC risk. HIF1A rs2057482 single nucleotide polymorphism (SNP) was genotyped in 410 PDAC cases and 490 healthy controls. The CC genotype SNP HIF1A is significantly correlated with PDAC risk (OR = 1.719, 95% CI: 1.293-2.286) and shorter overall survival (OS, P<0.0001) compared with the CT/TT alleles group. The C/T variants of rs2057482, a SNP located near the miR-199a binding site in HIF1A, could lead to differential regulation of HIF1A by miR-199a. Specifically, the C allele of rs2057482 weakened miR-199a-induced repression of HIF-1alpha expression on both mRNA and protein levels. In the PDAC tissue, individuals with the rs2057482-CC genotype expressed significantly higher levels of HIF-1alpha protein than those with the rs2057482-CT/TT genotype (P<0.0001). Both the CC genotype of SNP HIF1A and increased HIF-1alpha expression are significantly associated with shorter OS of patients with PDAC. After adjusted by TNM staging, differentiation grade, and the levels of CA19-9, both SNP HIF1A and HIF-1alpha expression retained highly significance on OS (P<0.0001). Taken together, our study demonstrates that host genetic variants could disturb the regulation of the miR-199a/HIF1A regulatory loop and alter PDAC risk and poor prognosis. In conclusion, the rs2057482-CC genotype increases the susceptibility to PDAC and associated with cancer progression. PMID- 26872371 TI - Competing endogenous RNA networks in human cancer: hypothesis, validation, and perspectives. AB - Non-coding RNAs represent a majority of the human transcriptome. However, less is known about the functions and regulatory mechanisms of most non-coding species. Moreover, little is known about the potential non-coding functions of coding RNAs. The competing endogenous RNAs (ceRNAs) hypothesis is proposed recently. This hypothesis describes potential communication networks among all transcript RNA species mediated by miRNAs and miRNA-recognizing elements (MREs) within RNA transcripts. Here we review the evolution of the ceRNA hypothesis, summarize the validation experiments and discusses the significance and perspectives of this hypothesis in human cancer. PMID- 26872368 TI - Cell polarity signaling in the plasticity of cancer cell invasiveness. AB - Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42. In epithelial tissues, their mutual interplay ensures apico-basal and planar cell polarity. Accordingly, altered functions of these polarity determinants lead to disrupted cell-cell adhesions, cytoskeleton rearrangements and overall loss of epithelial homeostasis. Polarity proteins are further engaged in diverse interactions that promote the establishment of front-rear polarity, and they help cancer cells to adopt different invasion modes. Invading cancer cells can employ either the collective, mesenchymal or amoeboid invasion modes or actively switch between them and gain intermediate phenotypes. Elucidation of the role of polarity proteins during these invasion modes and the associated transitions is a necessary step towards understanding the complex problem of metastasis. In this review we summarize the current knowledge of the role of cell polarity signaling in the plasticity of cancer cell invasiveness. PMID- 26872372 TI - Beyond evidence-based data: scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma. AB - The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long term response, and to preserve quality of life (QOL), minimizing treatment related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC. PMID- 26872373 TI - DARPP-32: from neurotransmission to cancer. AB - Dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32), also known as phosphoprotein phosphatase-1 regulatory subunit 1B (PPP1R1B), was initially discovered as a substrate of dopamine-activated protein kinase A (PKA) in the neostriatum in the brain. While phosphorylation at Thr-34 by PKA converts DARPP 32 into a potent inhibitor of protein phosphatase 1 (PP1), phosphorylation at Thr 75 transforms DARPP-32 into an inhibitor of PKA. Through regulation of DARPP-32 phosphorylation and modulation of protein phosphatase and kinase activities, DARPP-32 plays a critical role in mediating the biochemical, electrophysiological, and behavioral effects controlled by dopamine and other neurotransmitters in response to drugs of abuse and psychostimulants. Altered expression of DARPP-32 and its truncated isoform (t-DARPP), specifically in the prefrontal cortex, has been associated with schizophrenia and bipolar disorder. Moreover, cleavage of DARPP-32 by calpain has been implicated in Alzheimer's disease. Amplification of the genomic locus of DARPP-32 at 17q12 has been described in several cancers. DARPP-32 and t-DARPP are frequently overexpressed at the mRNA and protein levels in adenocarcinomas of the breast, prostate, colon, and stomach. Several studies demonstrated the pro-survival, pro-invasion, and pro angiogenic functions of DARPP-32 in cancer. Overexpression of DARPP-32 and t DARPP also promotes chemotherapeutic drug resistance and cell proliferation in gastric and breast cancers through regulation of pro-oncogenic signal transduction pathways. The expansion of DARPP-32 research from neurotransmission to cancer underscores the broad scope and implication of this protein in disparate human diseases. PMID- 26872374 TI - Metastatic pathway-specific transcriptome analysis identifies MFSD4 as a putative tumor suppressor and biomarker for hepatic metastasis in patients with gastric cancer. AB - Gastric cancer (GC) with hepatic metastasis remains a fatal disease. Global expression profiling was conducted using tissues from patients who had GC with synchronous hepatic metastasis, and major facilitator superfamily domain containing 4 (MFSD4) was identified as a candidate biomarker for hepatic metastasis in GC. Functional and expression analyses of this molecule in GC cell lines and clinical samples were conducted. We analyzed MFSD4 expression, DNA methylation, and copy number. RNA interference experiments evaluated the effects of MFSD4 expression on cell phenotype and apoptosis. We analyzed tissues of 200 patients with GC to assess the diagnostic performance of MFSD4 levels for predicting hepatic recurrence, metastasis, or both. Differential expression of MFSD4 mRNA by GC cell lines correlated positively with the levels of NUDT13 and OCLN mRNAs and inversely with those of BMP2. Hypermethylation of the MFSD4 promoter was detected in cells with lower levels of MFSD4 mRNA. Inhibition of MFSD4 expression significantly increased the invasiveness and motility of GC cells but did not influence cell proliferation or apoptosis. MFSD4 mRNA levels in primary GC tissues were reduced in patients with concomitant hepatic metastasis or recurrence compared with those without. Low levels of MFSD4 mRNA in primary GC tissues were an independent risk factor of hepatic recurrence and metastasis. MFSD4 expression in gastric tissues may represent a useful biomarker for identification of patients at high risk for hepatic recurrence, metastasis, or both. PMID- 26872375 TI - Regulation of laryngeal squamous cell cancer progression by the lncRNA H19/miR 148a-3p/DNMT1 axis. AB - Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer. The regulation of LSCC progression by long non-coding RNA (lncRNA) was not well understood. In this study, we reported that the lncRNA H19 was upregulated in LSCC. The expression levels of H19 were inversely correlated with the survival rate of LSCC patients. Knockdown of H19 expression inhibited LSCC cell migration, invasion and proliferation. We identified microRNA miR-148a-3p as an inhibitory target for H19. Overexpression of miR-148a-3p reduced LSCC migration, invasion and proliferation cell, while inhibition of miR-148a-3p did the opposite. The inhibition of LSCC progression induced by H19 knockdown required the activity of miR-148a-3p. We also identified DNA methyltransferase enzyme DNMT1 as a target of miR-148a-3p. Cellular DNA methylation levels were inhibited by both miR-148a-3p overexpression and H19 knockdown. In summary, our study demonstrated that the lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1. PMID- 26872376 TI - Enhanced eryptosis contributes to anemia in lung cancer patients. AB - OBJECTIVES: Anemia is a common complication of malignancy, which could result from either compromised erythropoiesis or decreased lifespan of circulating erythrocytes. Premature suicidal erythrocyte death, characterized by cell shrinkage and phosphatidylserine (PS) externalization, decreases erythrocyte lifespan and could thus cause anemia. Here, we explored whether accelerated eryptosis participates in the pathophysiology of anemia associated with lung cancer (LC) and its treatment. METHODS: Erythrocytes were drawn from healthy volunteers and LC patients with and without cytostatic treatment. PS exposure (annexin V-binding), cell volume (forward scatter), cytosolic Ca2+ (Fluo3 fluorescence), reactive oxygen species (ROS) production (DCFDA fluorescence) and ceramide formation (anti-ceramide antibody) were determined by flow cytometry. RESULTS: Hemoglobin concentration and hematocrit were significantly lower in LC patients as compared to healthy controls, even though reticulocyte number was higher in LC (3.0+/-0.6%) than in controls (1.4+/-0.2%). The percentage of PS exposing erythrocytes was significantly higher in LC patients with (1.4+/-0.1%) and without (1.2+/-0.3%) cytostatic treatment as compared to healthy controls (0.6+/-0.1%). Erythrocyte ROS production and ceramide abundance, but not Fluo3 fluorescence, were significantly higher in freshly drawn erythrocytes from LC patients than in freshly drawn erythrocytes from healthy controls. PS exposure of erythrocytes drawn from healthy volunteers was significantly more pronounced following incubation in plasma from LC patients than following incubation in plasma from healthy controls. CONCLUSIONS: Anemia in LC patients with and without cytostatic treatment is paralleled by increased eryptosis, which is triggered, at least in part, by increased oxidative stress and ceramide formation. PMID- 26872378 TI - The expression of presenilin 1 enhances carcinogenesis and metastasis in gastric cancer. AB - Presenilin 1 (PS-1, encoded by PSEN1) is a part of the gamma- (gamma-) secretase complex. Mutations in PSEN1 cause the majority of cases of familial Alzheimer's disease (FAD). Although in recent years PS-1 has been implicated as a tumor enhancer in various cancers, nothing is known regarding its role in gastric cancer (GC). In the present study, we investigate the role and clinical significance of PS-1 in GC. We observed that PS-1 was significantly upregulated and amplified in GC tissues and cell lines, and its aberrant expression was positively correlated with lymph node metastasis and with poor overall survival. Furthermore, PS-1 promoted tumor invasion and metastasis of GC both in vitro and vivo without affecting the proliferation of GC cells (MGC-803 and MKN-45). The results of treatment with the gamma-secretase inhibitor DAPT were consistent with the outcomes of PS-1 silencing. PS-1/gamma-secretase cleaves E-cadherin and releases its bound protein partner, beta-catenin, from the actin cytoskeleton, thereby allowing it to translocate into the nucleus and to activate the TCF/LEF-1 transcriptional activator, which may promote GC invasion and metastasis.In conclusion, PS-1 promotes invasion and metastasis in GC and may represent a novel prognostic biomarker and potential therapeutic target for GC treatment. PMID- 26872377 TI - Crosstalk between RON and androgen receptor signaling in the development of castration resistant prostate cancer. AB - Castrate-resistant prostate cancer (CRPC) is the fatal form of prostate cancer. Although reactivation of androgen receptor (AR) occurs following androgen deprivation, the precise mechanism involved is unclear. Here we show that the receptor tyrosine kinase, RON alters mechanical properties of cells to influence epithelial to mesenchymal transition and functions as a transcription factor to differentially regulate AR signaling. RON inhibits AR activation and subset of AR regulated transcripts in androgen responsive LNCaP cells. However in C4-2B, a castrate-resistant sub-line of LNCaP and AR-negative androgen independent DU145 cells, RON activates subset of AR-regulated transcripts. Expression of AR in PC-3 cells leads to activation of RON under androgen deprivation but not under androgen proficient conditions implicating a role for RON in androgen independence. Consistently, RON expression is significantly elevated in castrate resistant prostate tumors. Taken together our results suggest that RON activation could aid in promoting androgen independence and that inhibition of RON in combination with AR antagonist(s) merits serious consideration as a therapeutic option during hormone deprivation therapy. PMID- 26872379 TI - Dioxonaphthoimidazoliums AB1 and YM155 disrupt phosphorylation of p50 in the NF kappaB pathway. AB - The NF-kappaB pathway is overexpressed in non-small cell lung cancers (NSCLC) and contributes to the poor prognosis and high mortality characterizing this malignancy. Silencing the p50 and p65 NF-kappaB subunits in the NSCLC H1299 cell line led to profound loss in cell viability and downregulated anti-apoptotic proteins survivin and Mcl1. We also showed that a survivin suppressant, the dioxonaphthoimidazolium YM155, and its structural analog AB1 arrested the growth of H1299 cells at nanomolar concentrations. Both compounds were apoptogenic and suppressed survivin and other anti-apoptotic proteins (Mcl1, Bcl-2, Bcl-xl) in a dose- and/or time-dependent manner. YM155 and AB1 did not affect the expression of key proteins (IkappaBalpha, p65, p50) involved in NF-kappaB signaling. Stable IkappaBalpha levels suggest that the NF-kappaB/IkappaB complex and proteins upstream of IkappaBalpha, were not targeted. Neither did the compounds intercept the nuclear translocation of the p50 and p65 subunits. On the other hand, YM155 and AB1 suppressed the phosphorylation of the p50 subunit at Ser337 which is critical in promoting the binding of NF-kappaB dimers to DNA. Both compounds duly impeded the binding of NF-kappaB dimers to DNA and attenuated transcriptional activity of luciferase-transfected HEK293 cells controlled by NF-kappaB response elements. We propose that the "silencing" the NF-kappaB pathway effected by these compounds contributed to their potent apoptogenic effects on H1299. Notwithstanding, the mechanism(s) involved in their ability to abolish phosphorylation of p50 remains to be elucidated. Taken together, these results disclose a novel facet of functionalized dioxonaphthoimidazoliums that could account for their potent cell killing property. PMID- 26872380 TI - Inhibition of deubiquitinases primes glioblastoma cells to apoptosis in vitro and in vivo. AB - It remains a challenge in oncology to identify novel drug regimens to efficiently tackle glioblastoma, the most common primary brain tumor in adults. Here, we target deubiquitinases for glioblastoma therapy by utilizing the small-molecule inhibitor WP1130 which has been characterized as a deubiquitinase inhibitor that interferes with the function of Usp9X. Expression analysis data confirm that Usp9X expression is increased in glioblastoma compared to normal brain tissue indicating its potential as a therapeutic. Consistently, increasing concentrations of WP1130 decrease the cellular viability of established, patient derived xenograft (PDX) and stem cell-like glioblastoma cells. Specific down regulation of Usp9X reduces viability in glioblastoma cells mimicking the effects of WP1130. Mechanistically, WP1130 elicits apoptosis and increases activation of caspases. Moreover, WP1130 and siRNAs targeting Usp9X reduce the expression of anti-apoptotic Bcl-2 family members and Inhibitor of Apoptosis Proteins, XIAP and Survivin. Pharmacological and genetic interference with Usp9X efficiently sensitized glioblastoma cells to intrinsic and extrinsic apoptotic stimuli. In addition, single treatment with WP1130 elicited anti-glioma activity in an orthotopic proneural murine model of glioblastoma. Finally, the combination treatment of WP1130 and ABT263 inhibited tumor growth more efficiently than each reagent by its own in vivo without detectable side effects or organ toxicity. Taken together, these results suggest that targeting deubiquitinases for glioma therapy is feasible and effective. PMID- 26872381 TI - Hypoxia induces TFE3 expression in head and neck squamous cell carcinoma. AB - To assess the role of transcription factor MUE3 (TFE3) in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC), human HNSCC tissue arrays were investigated for TFE3 expression. Human HNSCC tissues with neoadjuvant inductive chemotherapey (docetaxel, cisplatin and fluorouracil, TPF) and mice HNSCC tissues from transgenic mice model were evaluated for TFE3 expression and the hypoxia pathway. The roles of EGF/EGFR mediated hypoxia in TFE3 nuclear expression were analyzed in vitro and in vivo. TFE3 expression was higher in human HNSCC tissues compared with that in normal oral mucosa. Moreover, high TFE3 expression was related to HIF-1alpha, PAI-1, and EGFR, which demonstrated the activation of the hypoxia pathway in HNSCC tissues. Furthermore, elevated TFE3 expression was observed in HNSCC after cisplatin-based chemotherapy, and high TFE3 expression may indicate poor response to TPF inductive chemotherapy. Furthermore, similar changes with increased TFE3 were observed in HNSCC of the transgenic mouse HNSCC model. Hypoxic culture in the human HNSCC cell line increased TFE3 expression, which promoted cell survival under hypoxia. EGFR inhibiton by cetuximab could attenuate hypoxia-induced TFE3 in the HNSCC cell line and transgenic mouse HNSCC model. These findings indicated that TFE3 was an important hypoxia-induced transcriptional factor in HNSCC. TFE3 could be regarded as a durgable therapeutic oncotarget by EGFR inhibition. PMID- 26872383 TI - A strategy to eradicate well-developed Krebs-2 ascites in mice. AB - We describe the strategy, which allows curing experimental mice engrafted with Krebs-2 ascites. The strategy is based on the facts that i) Krebs-2 tumor initiating stem cells (TISCs) are naturally capable of internalizing fragments of extracellular double-stranded DNA (dsDNA); ii) upon delivery into TISCs, these dsDNA fragments interfere with the on-going DNA repair process so that TISCs either die or lose their tumorigenic potential. The following 3-step regimen of therapeutic procedures leading to eradication of Krebs-2 ascites is considered. Firstly, three timed injections of cyclophosphamide (CP) exactly matching the interstrand cross-link (ICL) repair phases that lead to synchronization of ascites cells in late S/G2/M. Secondly, additional treatment of ascites 18 hours post each CP injection (at NER/HR transition timepoint) with a composite dsDNA based preparation interfering with the NER and HR repair pathways, so that tumorigenic properties of ascites cells are compromised. Thirdly, final treatment of mice with a combination of CP and dsDNA injections as ascites cells undergo apoptotic destruction, and the surviving TAMRA+ TISCs arrested in late S/G2/M phases massively enter into G1/S, when they regain sensitivity to CP+dsDNA treatment. Thus, this regimen assures that no viable cells, particularly Krebs-2 TISCs, remain. PMID- 26872382 TI - The E1B19K-deleted oncolytic adenovirus mutant AdDelta19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11. AB - Adenovirus-mediated sensitization of cancer cells to cytotoxic drugs depends on simultaneous interactions of early viral genes with cell death and survival pathways. It is unclear what cellular factors mediate these interactions in the presence of DNA-damaging drugs. We found that adenovirus prevents Chk1-mediated checkpoint activation through inactivation of Mre11 and downregulation of the pChk1 adaptor-protein, Claspin, in cells with high levels of DNA-damage induced by the cytotoxic drugs gemcitabine and irinotecan. The mechanisms for Claspin downregulation involve decreased transcription and increased degradation, further attenuating pChk1-mediated signalling. Live cell imaging demonstrated that low doses of gemcitabine caused multiple mitotic aberrations including multipolar spindles, micro- and multi-nucleation and cytokinesis failure. A mutant virus with the anti-apoptotic E1B19K-gene deleted (AdDelta19K) further enhanced cell killing, Claspin downregulation, and potentiated drug-induced DNA damage and mitotic aberrations. Decreased Claspin expression and inactivation of Mre11 contributed to the enhanced cell killing in combination with DNA-damaging drugs. These results reveal novel mechanisms that are utilised by adenovirus to ensure completion of its life cycle in the presence of cellular DNA damage. Taken together, our findings reveal novel cellular targets that may be exploited when developing improved anti-cancer therapeutics. PMID- 26872385 TI - Loss of Acetylcholine Signaling Reduces Cell Clearance Deficiencies in Caenorhabditis elegans. AB - The ability to eliminate undesired cells by apoptosis is a key mechanism to maintain organismal health and homeostasis. Failure to clear apoptotic cells efficiently can cause autoimmune diseases in mammals. Genetic studies in Caenorhabditis elegans have greatly helped to decipher the regulation of apoptotic cell clearance. In this study, we show that the loss of levamisole sensitive acetylcholine receptor, but not of a typical neuronal acetylcholine receptor causes a reduction in the number of persistent cell corpses in worms suffering from an engulfment deficiency. This reduction is not caused by impaired or delayed cell death but rather by a partial restoration of the cell clearance capacity. Mutants in acetylcholine turn-over elicit a similar phenotype, implying that acetylcholine signaling is the process responsible for these observations. Surprisingly, tissue specific RNAi suggests that UNC-38, a major component of the levamisole-sensitive receptor, functions in the dying germ cell to influence engulfment efficiency. Animals with loss of acetylcholine receptor exhibit a higher fraction of cell corpses positive for the "eat-me" signal phosphatidylserine. Our results suggest that modulation by ion channels of ion flow across plasma membrane in dying cells can influence the dynamics of phosphatidylserine exposure and thus clearance efficiency. PMID- 26872384 TI - Sequencing, De Novo Assembly, and Annotation of the Transcriptome of the Endangered Freshwater Pearl Bivalve, Cristaria plicata, Provides Novel Insights into Functional Genes and Marker Discovery. AB - BACKGROUND: The freshwater mussel Cristaria plicata (Bivalvia: Eulamellibranchia: Unionidae), is an economically important species in molluscan aquaculture due to its use in pearl farming. The species have been listed as endangered in South Korea due to the loss of natural habitats caused by anthropogenic activities. The decreasing population and a lack of genomic information on the species is concerning for environmentalists and conservationists. In this study, we conducted a de novo transcriptome sequencing and annotation analysis of C. plicata using Illumina HiSeq 2500 next-generation sequencing (NGS) technology, the Trinity assembler, and bioinformatics databases to prepare a sustainable resource for the identification of candidate genes involved in immunity, defense, and reproduction. RESULTS: The C. plicata transcriptome analysis included a total of 286,152,584 raw reads and 281,322,837 clean reads. The de novo assembly identified a total of 453,931 contigs and 374,794 non-redundant unigenes with average lengths of 731.2 and 737.1 bp, respectively. Furthermore, 100% coverage of C. plicata mitochondrial genes within two unigenes supported the quality of the assembler. In total, 84,274 unigenes showed homology to entries in at least one database, and 23,246 unigenes were allocated to one or more Gene Ontology (GO) terms. The most prominent GO biological process, cellular component, and molecular function categories (level 2) were cellular process, membrane, and binding, respectively. A total of 4,776 unigenes were mapped to 123 biological pathways in the KEGG database. Based on the GO terms and KEGG annotation, the unigenes were suggested to be involved in immunity, stress responses, sex determination, and reproduction. A total of 17,251 cDNA simple sequence repeats (cSSRs) were identified from 61,141 unigenes (size of >1 kb) with the most abundant being dinucleotide repeats. CONCLUSIONS: This dataset represents the first transcriptome analysis of the endangered mollusc, C. plicata. The transcriptome provides a comprehensive sequence resource for the conservation of genetic information in this species and enrichment of the genetic database. The development of molecular markers will assist in the genetic improvement of C. plicata. PMID- 26872386 TI - Prefrontal Lobe Brain Reserve Capacity with Resistance to Higher Global Amyloid Load and White Matter Hyperintensity Burden in Mild Stage Alzheimer's Disease. AB - BACKGROUND: Amyloid deposition and white matter lesions (WMLs) in Alzheimer's disease (AD) are both considered clinically significant while a larger brain volume is thought to provide greater brain reserve (BR) against these pathological effects. This study identified the topography showing BR in patients with mild AD and explored the clinical balances among BR, amyloid, and WMLs burden. METHODS: Thirty patients with AD were enrolled, and AV-45 positron emission tomography was conducted to measure the regional standardized uptake value ratio (SUVr) in 8 cortical volumes-of- interests (VOIs). The quantitative WMLs burden was measured from magnetic resonance imaging while the normalized VOIs volumes represented BR in this study. The cognitive test represented major clinical correlates. RESULTS: Significant correlations between the prefrontal volume and global (r = 0.470, p = 0.024), but not regional (r = 0.264, p = 0.223) AV-45 SUVr were found. AD patients having larger regional volume in the superior- (r = 0.572, p = 0.004), superior medial- (r = 0.443, p = 0.034), and middle prefrontal (r = 0.448, p = 0.032) regions had higher global AV-45 SUVr. For global WML loads, the prefrontal (r = -0.458, p = 0.019) and hippocampal volume (r = -0.469, p = 0.016) showed significant correlations while the prefrontal (r = -0.417, p = 0.043) or hippocampal volume (r = -0.422, p = 0.04) also predicted better composite memory scores. There were no interactions between amyloid SUVr and WML loads on the prefrontal volume. CONCLUSIONS: BR of the prefrontal region might modulate the adverse global pathological burden caused by amyloid deposition. While prefrontal volume positively associated with hippocampal volume, WMLs had an adverse impact on the hippocampal volume that predicts memory performance in mild stage AD. PMID- 26872387 TI - Population Genetics of Plasmodium vivax in Four Rural Communities in Central Vietnam. AB - BACKGROUND: The burden of malaria in Vietnam has drastically reduced, prompting the National Malaria Control Program to officially engage in elimination efforts. Plasmodium vivax is becoming increasingly prevalent, remaining a major problem in the country's central and southern provinces. A better understanding of P. vivax genetic diversity and structure of local parasite populations will provide baseline data for the evaluation and improvement of current efforts for control and elimination. The aim of this study was to examine the population genetics and structure of P. vivax isolates from four communities in Tra Leng commune, Nam Tra My district in Quang Nam, Central Vietnam. METHODOLOGY/PRINCIPAL FINDINGS: P. vivax mono infections collected from 234 individuals between April 2009 and December 2010 were successfully analyzed using a panel of 14 microsatellite markers. Isolates displayed moderate genetic diversity (He = 0.68), with no significant differences between study communities. Polyclonal infections were frequent (71.4%) with a mean multiplicity of infection of 1.91 isolates/person. Low but significant genetic differentiation (FST value from -0.05 to 0.18) was observed between the community across the river and the other communities. Strong linkage disequilibrium ([Formula: see text] = 0.113, p < 0.001) was detected across all communities, suggesting gene flow within and among them. Using multiple approaches, 101 haplotypes were grouped into two genetic clusters, while 60.4% of haplotypes were admixed. CONCLUSIONS/SIGNIFICANCE: In this area of Central Vietnam, where malaria transmission has decreased significantly over the past decade, there was moderate genetic diversity and high occurrence of polyclonal infections. Local human populations have frequent social and economic interactions that facilitate gene flow and inbreeding among parasite populations, while decreasing population structure. Findings provide important information on parasites populations circulating in the study area and are relevant to current malaria elimination efforts. PMID- 26872388 TI - Effect of Ethanol on the Metabolic Characteristics of HIV-1 Integrase Inhibitor Elvitegravir and Elvitegravir/Cobicistat with CYP3A: An Analysis Using a Newly Developed LC-MS/MS Method. AB - Elvitegravir (EVG), an integrase inhibitor for the treatment HIV infection, is increasingly becoming the part of first-line antiretroviral therapy (ART) regimen. EVG is mainly metabolized through cytochrome P450 (CYP) 3A4. Previously, we have shown that ethanol alters ART-CYP3A4 interactions with protease inhibitors thereby altering their metabolisms. However, as EVG is a fairly new class of drug, its kinetic characteristics and the effect of ethanol on EVG CYPP3A4 interaction is poorly understood. In this study, we characterized EVG and cobicistat (COBI)-boosted EVG metabolism in human microsomes followed by ethanol EVG, ethanol-COBI-EVG interaction with CYP3A. First, we developed and validated a simple, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC MS/MS) method for the quantification of EVG in the human liver microsomes. The lower limit of quantification for the drug was at 0.003 MUM (1.34 ng/ml). Extraction yield, matrix effects, drug stability, and calibration curves for the proposed method were validated according to the FDA guidelines. Time dependent kinetics data showed that 20mM ethanol decreases the apparent half-life of EVG degradation by ~50% compared to EVG alone. Our substrate kinetic results revealed that ethanol mildly decreases the catalytic efficiency for EVG metabolism. Inhibition studies demonstrated that EVG inhibits CYP3A4, and 20 mM ethanol causes a decrease in the IC50 of EVG. However, in the presence of COBI we were unable to determine these parameters effectively because COBI, being a strong inhibitor of CYP3A4, blocked the EVG/ethanol-CYP3A4 interactions. Docking studies predicted a shift of EVG or COBI binding to the active site of CYP3A4 in the presence of ethanol. Taken together, these results suggest that ethanol interacts with microsomal CYP3A and alters EVG-CYP3A4 interaction thereby altering EVG metabolism and inhibition of CYP3A4 by EVG. This finding has clinical significance because alcohol use is highly prevalent in HIV population, and there are no separate guidelines for these patients while they are on ART medication. PMID- 26872389 TI - The Impact of Hyperthermia on Receptor-Mediated Interleukin-6 Regulation in Mouse Skeletal Muscle. AB - In inflammatory cells, hyperthermia inhibits lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) gene expression and protein secretion. Since hyperthermia alone stimulates IL-6 in skeletal muscle, we hypothesized that it would amplify responses to other receptor-mediated stimuli. IL-6 regulation was tested in C2C12 myotubes and in soleus during treatment with epinephrine (EPI) or LPS. In EPI treated myotubes (100 ng/ml), 1 h exposure at 40.5 degrees C-42 degrees C transiently increased IL-6 mRNA compared to EPI treatment alone at 37 degrees C. In LPS-treated myotubes (1 MUg/ml), exposure to 41 degrees C-42 degrees C also increased IL-6 mRNA. In isolated mouse soleus, similar amplifications of IL-6 gene expression were observed in 41 degrees C, during both low (1 ng/ml) and high dose (100 ng/ml) EPI, but only in high dose LPS (1 MUg/ml). In myotubes, heat increased IL-6 secretion during EPI exposure but had no effect or inhibited secretion with LPS. In soleus there were no effects of heat on IL-6 secretion during either EPI or LPS treatment. Mechanisms for the effects of heat on IL-6 mRNA were explored using a luciferase-reporter in C2C12 myotubes. Overexpression of heat shock factor-1 (HSF-1) had no impact on IL-6 promoter activity during EPI stimulation, but elevated IL-6 promoter activity during LPS stimulation. In contrast, when the activator protein-1 (AP-1) element was mutated, responses to both LPS and EPI were suppressed in heat. Using siRNA against activating transcription factor-3 (ATF-3), a heat-stress-induced inhibitor of IL-6, no ATF-3 dependent effects were observed. The results demonstrate that, unlike inflammatory cells, hyperthermia in muscle fibers amplifies IL-6 gene expression to EPI and LPS. The effect appears to reflect differential engagement of HSF-1 and AP-1 sensitive elements on the IL-6 gene, with no evidence for involvement of ATF-3. The functional significance of increased IL-6 mRNA expression during heat may serve to overcome the well-known suppression of protein synthetic pathways occurring during heat shock. PMID- 26872390 TI - Cognition and Behaviour in Sotos Syndrome: A Systematic Review. AB - BACKGROUND: Research investigating cognition and behaviour in Sotos syndrome has been sporadic and to date, there is no published overview of study findings. METHOD: A systematic review of all published literature (1964-2015) presenting empirical data on cognition and behaviour in Sotos syndrome. Thirty four journal articles met inclusion criteria. Within this literature, data relating to cognition and/or behaviour in 247 individuals with a diagnosis of Sotos syndrome were reported. Ten papers reported group data on cognition and/or behaviour. The remaining papers employed a case study design. RESULTS: Intelligence quotient (IQ) scores were reported in twenty five studies. Intellectual disability (IQ < 70) or borderline intellectual functioning (IQ 70-84) was present in the vast majority of individuals with Sotos syndrome. Seven studies reported performance on subscales of intelligence tests. Data from these studies indicate that verbal IQ scores are consistently higher than performance IQ scores. Fourteen papers provided data on behavioural features of individuals with Sotos syndrome. Key themes that emerged in the behavioural literature were overlap with ASD, ADHD, anxiety and high prevalence of aggression/tantrums. CONCLUSION: Although a range of studies have provided insight into cognition and behaviour in Sotos syndrome, specific profiles have not yet been fully specified. Recommendations for future research are provided. PMID- 26872391 TI - [The meaning of hospitalization from the perspective of the caregiver: A qualitative study]. AB - OBJECTIVES: Knowing the meaning of hospitalization for the family caregiver of the hospitalized sick person. METHOD: Qualitative study using grounded theory. Participants were included if they met the following criteria: a) being part of the family; b) the sick person was admitted into a hospital in the state of Chihuahua; and c) the hospitalized person was over 18 years old. Sampling was applied by purpose. Data collection was conducted through in-depth interviews with an opening question. Similarly, memos were applied in the process of gathering. The analysis applied was based on grounded theory, with an open, axial and selective coding, identifying the categories and subcategories. During the analysis process the method of constant comparison was applied. RESULTS: Eighteen participants were included; 16 of whom were female. The mean age was 48.11 years old. The core category was identified: "the naked soul", formed by the categories; "I deal with the disease" which describes the situations experienced by the caregiver during and after the hospitalization process; "wartime" makes reference to the family problems that develop or worsen during the hospitalization process; and "dancing in the storm" focuses on all the positive changes occurring in the primary caregiver. CONCLUSIONS: Hospitalization causes uncertainty in the caregiver. Nurses help facilitate the adaptation of the caregiver at baseline and identify their own strengths. PMID- 26872392 TI - [Detection of palliative care needs in an acute care hospital unit. Pilot study]. AB - OBJECTIVES: Previous to wider prevalence studies, we designed the present pilot study to assess concordance and time invested in patient evaluations using a palliative care needs assessment tool. We also sought to estimate the prevalence of palliative care needs in an acute care hospital unit. METHODS: A cross sectional study was carried out, 4 researchers (2 doctors and 2 nurses) independently assessed all inpatients in an acute care hospital unit in Manacor Hospital, Mallorca (Spain), using the validated tool NECPAL CCOMS-ICO(c), measuring time invested in every case. Another researcher revised clinical recordings to analise the sample profile. RESULTS: Every researcher assessed 29 patients, 15 men and 14 women, mean age 74,03 +/- 10.25 years. 4-observer concordance was moderate (Kappa 0,5043), tuning out to be higher between nurses. Mean time per patient evaluation was 1.9 to 7.72 minutes, depending on researcher. Prevalence of palliative care needs was 23,28%. CONCLUSIONS: Moderate concordance lean us towards multidisciplinary shared assessments as a method for future research. Avarage of time invested in evaluations was less than 8 minutes, no previous publications were identified regarding this variable. More than 20% of inpatients of the acute care unit were in need of palliative care. PMID- 26872393 TI - The cost-effectiveness of training US primary care physicians to conduct colorectal cancer screening in family medicine residency programs. AB - BACKGROUND: Demand for a wide array of colorectal cancer screening strategies continues to outpace supply. One strategy to reduce this deficit is to dramatically increase the number of primary care physicians who are trained and supportive of performing office-based colonoscopies or flexible sigmoidoscopies. This study evaluates the clinical and economic implications of training primary care physicians via family medicine residency programs to offer colorectal cancer screening services as an in-office procedure. METHODS: Using previously established clinical and economic assumptions from existing literature and budget data from a local grant (2013), incremental cost-effectiveness ratios are calculated that incorporate the costs of a proposed national training program and subsequent improvements in patient compliance. Sensitivity analyses are also conducted. RESULTS: Baseline assumptions suggest that the intervention would produce 2394 newly trained residents who could perform 71,820 additional colonoscopies or 119,700 additional flexible sigmoidoscopies after ten years. Despite high costs associated with the national training program, incremental cost-effectiveness ratios remain well below standard willingness-to-pay thresholds under base case assumptions. Interestingly, the status quo hierarchy of preferred screening strategies is disrupted by the proposed intervention. CONCLUSIONS: A national overhaul of family medicine residency programs offering training for colorectal cancer screening yields satisfactory incremental cost effectiveness ratios. However, the model places high expectations on primary care physicians to improve current compliance levels in the US. PMID- 26872394 TI - Recognition and detection of 8-oxo-rG in RNA using the DNA/OMeRNA chimera probes containing fluorescent adenosine-diazaphenoxazine analog. AB - Recent studies indicate that oxidative damage to RNA results in dysfunction of translation and eventual pathogenesis. A representative oxidized base in RNA is 8 hydroxyguanosine (8-oxo-rG), however, unlike its DNA counterpart (8-oxo-dG), its role in pathogenesis has not attracted much attention until recently. The 2' deoxyadenosine derivative with a diazaphenoxazine skeleton at the 6-amino group (Adap) was shown to be selective for 8-oxo-dG in DNA. In this study, the 2'-O methoxy derivative of Adap (2'-OMeAdap) was designed as a selective molecule for 8-oxo-rG in RNA. 8-Oxo-rG in the homopurine RNA was selectively recognized by the ODN probe incorporating Adap. In contrast, although it was not possible by the Adap-containing ODN prove due to the instability of the corresponding duplex, 8 oxo-rG in homopyrimidine RNA was selectively detected by the 2'-OMeRNA probe incorporating 2'-OMeAdap. PMID- 26872395 TI - Tandem Copper-Catalyzed Propargylation/Alkyne Azacyclization/Isomerization Reaction under Microwave Irradiation: Synthesis of Fully Substituted Pyrroles. AB - A copper-catalyzed and microwave-assisted synthesis of fully substituted pyrroles has been developed. A series of pentasubstituted pyrroles, especially alpha arylpyrroles, could be obtained in moderate to good yields (up to 93%) through a tandem propargylation/alkyne azacyclization/isomerization sequence from readily available beta-enamino compounds and propargyl acetates. PMID- 26872396 TI - Invited commentary: Differential learning is different from contextual interference learning. AB - There has been renewed interest in the detailed structure of what is learned and the boundary conditions that foster motor learning. The accompanying article by Hossner et al. (2016), particularly their findings about augmented feedback in the context of different levels of additional noise, is consistent with this focus. Unfortunately, the findings from Hossner and colleagues appear to be based on incorrect interpretations of the differential learning (DL) approach. Essential discrepancies in the experimental conditions suggest the basis for the deviating results obtained in comparison to those of the original DL experiments. In this comment, it is also shown that the author's assumptions and interpretations underlying CI and the DL approaches obscure crucial problems and contradictions of classical learning theory. PMID- 26872397 TI - Psychological Comorbidity and Inflammatory Bowel Disease Activity: Cause or Effect? PMID- 26872398 TI - Repeated Measurements of Hepatitis B Surface Antigen Identify Carriers of Inactive HBV During Long-term Follow-up. AB - BACKGROUND & AIMS: Measurements of hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA might help to identify carriers of inactive HBV. We assessed the performance of repeated measurements of HBsAg over a median time period of 8 years. METHODS: We performed a retrospective study of 292 HBe antigen negative patients with chronic HBV infection, normal levels of alanine aminotransferase (ALT), levels of HBV DNA <20,000 IU/mL, and no cirrhosis who visited the outpatient clinics at 8 tertiary care centers in Europe, Asia, and Australia from 1990 through 2011. Patients were determined to be carriers of inactive HBV (level of HBV DNA <2000 IU/mL and serum levels of ALT that remained normal) or to have HBV activity (level of HBV DNA fluctuating >2000 IU/mL and/or abnormal levels of ALT) after each year of follow-up. Patients were followed for a median time of 8 years (range, 4-9 years). Dynamic regression analysis was used to study changes in level of HBsAg and HBV phase and to update the risk of HBV activity. RESULTS: One year after study enrollment, 189 patients (65%) had inactive HBV and 103 patients (35%) had HBV activity. Based on dynamic analysis, the probability that a patient would have HBV at any following year differed according to level of HBsAg; odds were 97% for patients with initial level of HBsAg <100 IU/mL, 85% for patients with initial levels 100-1000 IU/mL, and 76% for patients with initial levels >1000 IU/mL (P < .001). Having inactive virus for any 2 consecutive years predicted having inactive virus in any third year. However, 15% of patients with level of HBsAg >100 IU/mL had HBV activity in the third year. The combination of HBsAg level <100 IU/mL and HBV DNA level <2000 IU/mL identified patients whose virus remained inactive for the entire follow-up period, with 98% specificity and a positive predictive value of 97%, for all HBV genotypes. Patients with HBV activity who had levels of HBV DNA <5000 IU/mL and decreases in HBsAg of 0.5 log IU/mL or more for 1 year had a high probability of becoming carriers of inactive HBV in the next year. CONCLUSIONS: In a retrospective, dynamic analysis of almost 300 patients with chronic HBV infection, we found that levels of HBsAg <100 IU/mL identify patients with inactive virus with a high level of specificity. HBsAg levels should therefore be used to define phases of HBV infection in HBe antigen-negative patients. PMID- 26872399 TI - Do Proton Pump Inhibitors Exacerbate Nonsteroidal Anti-Inflammatory Drug-Induced Small-Bowel Enteropathy? PMID- 26872400 TI - Molecular Biomarkers in the Personalized Treatment of Colorectal Cancer. AB - Colorectal cancer (CRC) is a disease in which pathogenesis is influenced by genetic and epigenetic events that occur with tumor initiation and progression. Large variation exists in individual patient prognosis and response to chemotherapy, caused by molecular heterogeneity. Certain biomarkers have been identified that can predict clinical outcome beyond tumor staging, and inform treatment selection. Molecular testing is routinely performed in clinical practice for the selection of patients for targeted biological agents or immunotherapy, and is advocated for prognostic stratification. Estimating prognosis can avoid undertreatment or overtreatment and also guide the intensity of patient follow-up. Classifiers of CRC have been developed that integrate genetic and/or epigenetic features. The mutational status of KRAS and BRAF(V600E) oncogenes combined with analysis of the DNA mismatch repair system with/without the CpG island methylator phenotype (CIMP) has been shown to identify colon cancer subtypes with distinct clinical features and prognoses. Gene expression profiling has also been used to subtype CRCs and can overcome the limitations of single/limited gene testing. A recent effort identified 4 consensus molecular subtypes of biological relevance that were associated with different patient outcomes. Efforts to validate and refine these subtypes to include additional genomic features are ongoing. The focus of this article is to highlight molecular markers that can inform clinical decision-making in patients with CRC. PMID- 26872401 TI - Optimize Thiopurine Therapy in Autoimmune Hepatitis. PMID- 26872402 TI - Distribution and Characteristics of Colonic Diverticula in a United States Screening Population. AB - BACKGROUND & AIMS: Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population. METHODS: We analyzed data from a prospective study of 624 patients (mean age, 54 years) undergoing screening colonoscopy at the University of North Carolina Hospital from 2013 through 2015. The examination included a detailed assessment of colonic diverticula. To assess the association between participant characteristics and diverticula, we used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Of our population, 260 patients (42%) had 1 or more diverticula (mean number, 14; range, 1-158). Participants with diverticula were more likely to be older, male, and have a higher body mass index than those without diverticula. The distribution of diverticula differed significantly by race. Among white persons, 75% of diverticula were in the sigmoid colon, 11% in the descending splenic flexure, 6% in the transverse colon, and 8% were in the ascending colon or hepatic flexure. In black persons 64% of diverticula were in the sigmoid colon, 8% in the descending colon or splenic flexure, 7% in the transverse colon, and 20% in the ascending colon or hepatic flexure (P = .0008). The proportion of patients with diverticula increased with age: 35% were 50 years or younger, 40% were 51-60 years, and 58% were older than 60 years. The proportion of patients with more than 10 diverticula increased with age: 8% were 50 years or younger, 15% were 51-60 years, and 30% were older than 60 years. CONCLUSIONS: Older individuals not only have a higher prevalence of diverticula than younger individuals, but also a greater density, indicating that this is a progressive disease. Black persons have a greater percentage of their diverticula in the proximal colon and fewer in the distal colon compared with white persons. Understanding the distribution and determinants of diverticula is the first step in preventing diverticulosis and its complications. PMID- 26872403 TI - Building Connections With Role Models Using an Appreciative Inquiry Approach. PMID- 26872404 TI - Extracellular vesicles in cardiovascular disease: are they Jedi or Sith? AB - In the recent past, extracellular vesicles have become recognized as important players in cell biology and biomedicine. Extracellular vesicles, including exosomes, microvesicles and apoptotic bodies, are phospholipid bilayer-enclosed structures found to be secreted by most if not all cells. Extracellular vesicle secretion represents a universal and highly conserved active cellular function. Importantly, increasing evidence supports that extracellular vesicles may serve as biomarkers and therapeutic targets or tools in human diseases. Cardiovascular disease undoubtedly represents one of the most intensely studied and rapidly growing areas of the extracellular vesicle field. However, in different studies related to cardiovascular disease, extracellular vesicles have been shown to exert diverse and sometimes discordant biological effects. Therefore, it might seem a puzzle whether these vesicles are in fact beneficial or detrimental to cardiovascular health. In this review we provide a general introduction to extracellular vesicles and an overview of their biological roles in cardiovascular diseases. Furthermore, we aim to untangle the various reasons for the observed discrepancy in biological effects of extracellular vesicles in cardiovascular diseases. To this end, we provide several examples that demonstrate that the observed functional diversity is in fact due to inherent differences among various types of extracellular vesicles. PMID- 26872405 TI - Circumscribed choroidal hemangioma: A case report and literature review. AB - Choroidal hemangioma is a rare congenital ocular tumor that can present as either circumscribed or diffuse. Circumscribed choroidal hemangioma (CCH) typically manifests as a red-orange mass within the posterior pole and appears similar to other ocular conditions, such as choroidal melanoma and choroidal metastasis. Proper diagnosis is crucial and is aided by the use of ancillary testing. CCH itself is benign but can cause secondary complications such as subretinal fluid accumulation and subsequent retinal detachment. If these conditions should arise, several treatment options are available. PMID- 26872406 TI - Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage. AB - BACKGROUND: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. OBJECTIVE: So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. METHOD: Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. RESULTS: During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 +/- 2.5 pg/ml and 4.29 +/- 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 +/- 0.87 pg/ml in the non-survival group and 6.64 +/- 1.89 pg/ml in the survival group. Furthermore, it was 10.22 +/- 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 +/- 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C reactive protein levels (p < 0.01 for all). CONCLUSION: The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management. PMID- 26872407 TI - Development of an IFNgamma ELISPOT for the analysis of the human T cell response against mumps virus. AB - In the last decade, mumps virus (MuV) causes outbreaks in highly vaccinated populations. Sub-optimal T cell immunity may play a role in the susceptibility to mumps in vaccinated individuals. T cell responses to mumps virus have been demonstrated, yet the quality of the MuV-specific T cell response has not been analyzed using single cell immunological techniques. Here we developed an IFNgamma ELISPOT assay to assess MuV-specific T cell responses in peripheral blood mononuclear cells (PBMC) of healthy (vaccinated) donors and mumps patients. Various in vitro MuV-specific stimulation methods of PBMC were compared, using either live or inactivated MuV alone or MuV-infected autologous antigen presenting cells, i.e. Epstein Barr Virus-transformed B lymphoblastoid cell lines (EBV-BLCL) or (mitogen pre-activated) PBMC, for their ability to recall IFNgamma producing responder cells measured by ELISPOT. For the detection of MuV-specific T cell responses, direct exposure (24h) to live MuV was the preferred stimulation method when assay sensitivity and practical reasons were considered. Notably, flowcytometric confirmation of data revealed that primarily T cells and NK cells produce IFNgamma upon live MuV stimulation. Depleting PBMC from CD56(+) NK cells prior to stimulation with live MuV led to the enumeration of MuV-specific T cell responses by ELISPOT. Our assay constitutes a tool to evaluate memory MuV specific T cell responses in MuV vaccinated or infected persons. Furthermore, this study provides evidence that live MuV not only induces IFNgamma production by T cells, but also by NK cells. PMID- 26872409 TI - Identification of methylglyoxal as a major mutagen in wood and bamboo pyroligneous acids. AB - To identify the major mutagen in pyroligneous acid (PA), 10 wood and 10 bamboo pyroligneous acids were examined using the Ames test in Salmonella typhimurium strains TA100 and TA98. Subsequently, the mutagenic dicarbonyl compounds (DCs), glyoxal, methylglyoxal (MG), and diacetyl in PA were quantified using high performance liquid chromatography, and the mutagenic contribution ratios for each DC were calculated relative to the mutagenicity of PA. Eighteen samples were positive for mutagens and showed the strongest mutagenicity in TA100 in the absence of S9 mix. MG had the highest mutagenic contribution ratio, and its presence was strongly correlated with the specific mutagenicity of PA. These data indicate that MG is the major mutagen in PA. PMID- 26872408 TI - Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study. AB - Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site's MR system, to determine a manufacturer specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys were higher than those of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study. PMID- 26872410 TI - Anti-inflammatory effects and molecular mechanisms of 8-prenyl quercetin. AB - SCOPE: 8-prenyl quercetin (PQ) is a typical prenylflavonoid distributed in plant foods. It shows higher potential bioactivity than its parent quercetin (Q) although the mechanisms are not fully understood. This study aims to clarify the anti-inflammatory effects and molecular mechanisms of PQ in cell and animal models, compared to Q. METHODS AND RESULTS: RAW264.7 cells were treated with PQ or Q to investigate the influence on the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and protein kinases by Western blotting. Nitric oxide (NO) and prostaglandin E2 (PGE2 ) were measured by the Griess method and ELISA, respectively. Cytokines were assayed by the multiplex technology. Mouse paw edema was induced by LPS. The results revealed that PQ had stronger inhibition on the production of iNOS, COX-2, NO, PGE2 , and 12 kinds of cytokines, than Q. PQ also showed in vivo anti-inflammatory effect by attenuating mouse paw edema. Molecular data revealed that PQ had no competitive binding to Toll-like receptor 4 with LPS, but directly targeted SEK1-JNK1/2 (where SEK is stress-activated protein kinase and JNK1/2 is Jun-N-terminal kinase 1/2) and MEK1 ERK1/2 (where ERK is extracellular signal regulated kinase). CONCLUSION: PQ as a potential inhibitor revealed anti-inflammatory effect in both cell and animal models at least by targeting SEK1-JNK1/2 and MEK1-ERK1/2. PMID- 26872411 TI - Effects of white-nose syndrome on regional population patterns of 3 hibernating bat species. AB - Hibernating bats have undergone severe recent declines across the eastern United States, but the cause of these regional-scale declines has not been systematically evaluated. We assessed the influence of white-nose syndrome (an emerging bat disease caused by the fungus Pseudogymnoascus destructans, formerly Geomyces destructans) on large-scale, long-term population patterns in the little brown myotis (Myotis lucifugus), the northern myotis (Myotis septentrionalis), and the tricolored bat (Perimyotis subflavus). We modeled population trajectories for each species on the basis of an extensive data set of winter hibernacula counts of more than 1 million individual bats from a 4-state region over 13 years and with data on locations of hibernacula and first detections of white-nose syndrome at each hibernaculum. We used generalized additive mixed models to determine population change relative to expectations, that is, how population trajectories differed with a colony's infection status, how trajectories differed with distance from the point of introduction of white-nose syndrome, and whether declines were concordant with first local observation of the disease. Population trajectories in all species met at least one of the 3 expectations, but none met all 3. Our results suggest, therefore, that white-nose syndrome has affected regional populations differently than was previously understood and has not been the sole cause of declines. Specifically, our results suggest that in some areas and species, threats other than white-nose syndrome are also contributing to population declines, declines linked to white-nose syndrome have spread across large geographic areas with unexpected speed, and the disease or other threats led to declines in bat populations for years prior to disease detection. Effective conservation will require further research to mitigate impacts of white nose syndrome, renewed attention to other threats to bats, and improved surveillance efforts to ensure early detection of white-nose syndrome. PMID- 26872412 TI - Functional ionotropic glutamate receptors on peripheral axons and myelin. AB - INTRODUCTION: Neurotransmitter-dependent signaling is traditionally restricted to axon terminals. However, receptors are present on myelinating glia, suggesting that chemical transmission may also occur along axons. METHODS: Confocal microscopy and Ca(2+) -imaging using an axonally expressed FRET-based reporter was used to measure Ca(2+) changes and morphological alterations in myelin in response to stimulation of glutamate receptors. RESULTS: Activation of alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors induced a Ca(2+) increase in axon cylinders. However, only the latter caused structural alterations in axons, despite similar Ca(2+) increases. Myelin morphology was significantly altered by NMDA receptor activation, but not by AMPA receptors. Cu(2+) ions influenced the NMDA receptor-dependent response, suggesting that this metal modulates axonal receptors. Glutamate increased ribosomal signal in Schwann cell cytoplasm. CONCLUSIONS: Axon cylinders and myelin of peripheral nervous system axons respond to glutamate, with a consequence being an increase in Schwann cell ribosomes. This may have implications for nerve pathology and regeneration. Muscle Nerve 54: 451-459, 2016. PMID- 26872413 TI - Interactive effects of temperature and glyphosate on the behavior of blue ridge two-lined salamanders (Eurycea wilderae). AB - The objective of the present study was to evaluate the potential interactive effects of stream temperatures and environmentally relevant glyphosate-based herbicide concentrations on movement and antipredator behaviors of larval Eurycea wilderae (Blue Ridge two-lined salamander). Larval salamanders were exposed to 1 of 4 environmentally relevant glyphosate concentrations (0.00 ug acid equivalent [a.e.]/L, 0.73 ug a.e./L, 1.46 ug a.e./L, and 2.92 ug a.e./L) at either ambient (12 degrees C) or elevated (23 degrees C) water temperature. Behaviors observed included the exploration of a novel habitat, use of refuge, habitat selection relative to a potential predator, and burst movement distance. In the absence of glyphosate, temperature consistently affected movement and refuge-use behavior, with individuals moving longer distances more frequently and using refuge less at warm temperatures; however, when glyphosate was added, the authors observed inconsistent effects of temperature that may have resulted from differential toxicity at various temperatures. Larval salamanders made shorter, more frequent movements and demonstrated reduced burst distance at higher glyphosate concentrations. The authors also found that lower glyphosate concentrations sometimes had stronger effects than higher concentrations (i.e., nonmonotonic dose responses), suggesting that standard safety tests conducted only at higher glyphosate concentrations might overlook important sublethal effects on salamander behavior. These data demonstrate that sublethal effects of glyphosate based herbicides on natural behaviors of amphibians can occur with short-term exposure to environmentally relevant concentrations. Environ Toxicol Chem 2016;35:2297-2303. (c) 2016 SETAC. PMID- 26872415 TI - Louse-borne relapsing fever among East African refugees in Europe. AB - Louse-borne relapsing fever a neglected and forgotten disease by western physicians has recently re-emerged among East African migrants seeking asylum in Europe. We review here the cases observed so far together with a critical reappraisal of several issues regarding clinical presentation, diagnosis and treatment. PMID- 26872414 TI - Post-chikungunya rheumatic disorders in travelers after return from the Caribbean. AB - BACKGROUND: Due to increasing concerns about post-chikungunya (pCHIK) rheumatic disorders in Latin America we aimed to evaluate its occurrence in travelers returning to NYC from the Caribbean. METHOD: Patients diagnosed with chikungunya (CHIK) during 2014 at the Bronx-Lebanon Hospital Center (Bronx, NewYork) were identified by reviewing laboratory and electronic medical records. Patients and caregivers of pediatric patients were interviewed by phone >=9 months after the CHIK diagnosis to survey for chronic symptomatology and current health care needs. Reported chronic musculoskeletal complaints were categorized according to validated criteria. RESULTS: A total of 28 patients (54% females, median age [range] of 51.5 [0, 88] years) diagnosed with CHIK at our center were identified. Most (82%) had returned from the Dominican Republic. Nineteen (68%) patients were successfully contacted at a median (range) of 13 (9, 16) months since the acute diagnosis. A third (37%) reported ongoing complaints related to CHIK including joint pain (32%), muscle pain (32%), and joint swelling (26%). A presumptive diagnosis of pCHIK chronic inflammatory arthritis (n = 4) and pCHIK musculoskeletal disorder (n = 3) was established. CONCLUSIONS: A third of travelers with CHIK acquired in the Caribbean may be at risk for developing persistent symptoms suggestive of pCHIK rheumatic disorder. PMID- 26872416 TI - Zika virus and the risk of imported infection in returned travelers: Implications for clinical care. AB - Since late 2015, an unprecedented outbreak of Zika virus is spreading quickly across Southern America. The large size of the current outbreak in The Americas will also result in an increase in Zika virus infections among travelers returning from endemic areas. We report five cases of imported Zika virus infection to The Netherlands. Although the clinical course is usually mild, establishing the diagnosis is important, mainly because of the association with congenital microcephaly and the possibility of sexual transmission. PMID- 26872417 TI - Paraproteinemic keratopathy as the presenting sign of hematologic malignancy. PMID- 26872418 TI - T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis. AB - Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona fide dendritic cells were virtually absent from the brain parenchyma of both non tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease. PMID- 26872419 TI - Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets. AB - Although poorly understood, early-life infection is predicted to affect brain microglial cells, making them hypersensitive to subsequent stimuli. To investigate this, we assessed gene expression in hippocampal tissue obtained from a previously published study reporting increased microglial cell activity and reduced hippocampal-dependent learning in neonatal piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus that induces interstitial pneumonia. Infection altered expression of 455 genes, of which 334 were up-regulated and 121 were down-regulated. Functional annotation revealed that immune function genes were enriched among the up-regulated differentially expressed genes (DEGs), whereas calcium binding and synaptic vesicle genes were enriched among the down-regulated DEGs. Twenty-six genes encoding part of the microglia sensory apparatus (i.e., the sensome) were up-regulated (e.g., IL1R1, TLR2, and TLR4), whereas 15 genes associated with the synaptosome and synaptic receptors (e.g., NPTX2, GABRA2, and SLC5A7) were down-regulated. As the sensome may foretell microglia reactivity, we next inoculated piglets with culture medium or PRRSV at PD 7 and assessed hippocampal microglia morphology and function at PD 28 when signs of infection were waning. Consistent with amplification of the sensome, microglia from PRRSV piglets had enhanced responsiveness to chemoattractants, increased phagocytic activity, and secreted more TNFalpha in response to lipopolysaccharide and Poly I:C. Immunohistochemical staining indicated PRRSV infection increased microglia soma length and length-to-width ratio. Bipolar rod-like microglia not evident in hippocampus of control piglets, were present in infected piglets. Collectively, this study suggests early-life infection alters the microglia sensome as well as microglial cell morphology and function. PMID- 26872420 TI - Self-rated health and interleukin-6: Longitudinal relationships in older adults. AB - BACKGROUND: Both self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic. OBJECTIVE: To study the between- and within-person associations between SRH and IL-6. METHODS: Older adults (N=131; Mage=75 years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6 months over a period up to 5 years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models. RESULTS: In bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p<.001) but not dynamic SRH (within-person changes; p=.93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model. CONCLUSIONS: Better stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH-IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted. PMID- 26872421 TI - Reduced number of peripheral natural killer cells in schizophrenia but not in bipolar disorder. AB - Overwhelming evidence indicates that subthreshold inflammatory state might be implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BPD). It has been reported that both groups of patients might be characterized by abnormal lymphocyte counts. However, little is known about alterations in lymphocyte proportions that may differentiate SCZ and BPD patients. Therefore, in this study we investigated blood cell proportions quantified by means of microarray expression deconvolution using publicly available data from SCZ and BPD patients. We found significantly lower counts of natural killer (NK) cells in drug-naive and medicated SCZ patients compared to healthy controls across all datasets. In one dataset from SCZ patients, there were no significant differences in the number of NK cells between acutely relapsed and remitted SCZ patients. No significant difference in the number of NK cells between BPD patients and healthy controls was observed in all datasets. Our results indicate that SCZ patients, but not BPD patients, might be characterized by reduced counts of NK cells. Future studies looking at lymphocyte counts in SCZ should combine the analysis of data obtained using computational deconvolution and flow cytometry techniques. PMID- 26872422 TI - Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors. AB - Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH. PMID- 26872423 TI - Peripheral elimination of the sympathetic nervous system stimulates immunocyte retention in lymph nodes and ameliorates collagen type II arthritis. AB - OBJECTIVES: In collagen type II-induced arthritis (CIA), early activation of the sympathetic nervous system (SNS) is proinflammatory. Here, we wanted to find new target organs contributing to proinflammatory SNS effects. In addition, we wanted to clarify the importance of SNS-modulated immunocyte migration. METHODS: A new technique termed spatial energy expenditure configuration (SEEC) was developed to demonstrate bodily areas of high energy demand (to find new targets). We studied homing of labeled cells in vivo, lymphocyte expression of CCR7, supernatant concentration of CCL21, and serum levels of sphingosine-1-phosphate (S1P) in sympathectomized control/arthritic animals. RESULTS: During the course of arthritis, SEEC identified an early marked increase of energy expenditure in draining lymph nodes and spleen (nowhere else!). Although early sympathectomy ameliorated later disease, early sympathectomy increased energy consumption, organ weight, and cell numbers in arthritic secondary lymphoid organs, possibly a sign of lymphocyte retention (also in controls). Elimination of the SNS retained lymph node cells, elevated expression of CCR7 on lymph node cells, and increased CCL21. Serum levels of S1P, an important factor for lymphocyte egress, were higher in arthritic than control animals. Sympathectomy decreased S1P levels in arthritic animals to control levels. Transfer of retained immune cells from draining lymph nodes of sympathectomized donors to sympathectomized recipients markedly increased arthritis severity over weeks. CONCLUSIONS: By using the SEEC technique, we identified draining lymph nodes and spleen as major target organs of the SNS. The data show that the SNS increases egress of lymphocytes from draining lymph nodes to stimulate arthritic inflammation. PMID- 26872424 TI - Oxidative mitigation of aquatic methane emissions in large Amazonian rivers. AB - The flux of methane (CH4 ) from inland waters to the atmosphere has a profound impact on global atmospheric greenhouse gas (GHG) levels, and yet, strikingly little is known about the dynamics controlling sources and sinks of CH4 in the aquatic setting. Here, we examine the cycling and flux of CH4 in six large rivers in the Amazon basin, including the Amazon River. Based on stable isotopic mass balances of CH4 , inputs and outputs to the water column were estimated. We determined that ecosystem methane oxidation (MOX) reduced the diffusive flux of CH4 by approximately 28-96% and varied depending on hydrologic regime and general geochemical characteristics of tributaries of the Amazon River. For example, the relative amount of MOX was maximal during high water in black and white water rivers and minimal in clear water rivers during low water. The abundance of genetic markers for methane-oxidizing bacteria (pmoA) was positively correlated with enhanced signals of oxidation, providing independent support for the detected MOX patterns. The results indicate that MOX in large Amazonian rivers can consume from 0.45 to 2.07 Tg CH4 yr(-1) , representing up to 7% of the estimated global soil sink. Nevertheless, climate change and changes in hydrology, for example, due to construction of dams, can alter this balance, influencing CH4 emissions to atmosphere. PMID- 26872425 TI - Predictive factors of self-reported hand eczema in adult Danes: a population based cohort study with 5-year follow-up. AB - BACKGROUND: Information about predictive factors of hand eczema is crucial for primary prevention. OBJECTIVES: To investigate predictive factors of hand eczema in adult Danes from the general population. METHODS: Participants from a cross sectional 5-year follow-up study in the general population, aged 18-72 years (n = 2270), completed questionnaires about skin health and were grouped into four hand eczema groups: 'never', 'incident', 'nonpersistent' and 'persistent'. Multiple logistic regression models adjusted for age group and sex were used to evaluate associations with baseline variables. The participation rate for the follow-up study was 66.5% (29.7% of the participants originally invited to the baseline study). RESULTS: A history of atopic dermatitis (AD) was associated with both persistent and incident hand eczema [odds ratio (OR) 9.0, 95% confidence interval (95% CI) 5.6-14.4 and OR 3.0, 95% CI 1.7-5.2, respectively]. Thus, even in adulthood, a history of AD should be considered as a predictor of incident hand eczema. While filaggrin gene (FLG) null mutations were not associated with incident hand eczema, a statistically significant association was observed with persistent hand eczema (OR 3.1, 95% CI 1.8-5.2). Finally, contact sensitization (23 allergens without nickel) was also associated with persistent hand eczema (OR 2.5, 95% CI 1.2-5.0), independently of a history of AD. CONCLUSIONS: This study confirms a history of AD as the strongest predictor of persistent hand eczema. We additionally found that a history of AD was associated with incident hand eczema in adults, in contrast to FLG mutations, which were associated only with persistent hand eczema in individuals with a history of AD, and not with incident hand eczema. Our study adds new knowledge to the interplay between AD, FLG mutations and hand eczema in the adult general population. PMID- 26872426 TI - Tocilizumab and pregnancy: Four cases of pregnancy in young women with rheumatoid arthritis refractory to anti-TNF biologics with exposure to tocilizumab. AB - OBJECTIVES: To investigate the use of tocilizumab (TCZ) in pregnant patients with active rheumatoid arthritis (RA) refractory to anti-tumour necrosis factor (TNF) agents. METHODS: We retrospectively analysed the medical records of pregnant women with active RA treated between July 2008 and January 2015 by the Division of Maternal Medicine at our hospital. Inclusion criteria for this case series included active RA refractory to anti-TNF agents and exposure to TCZ at the time of conception. RESULTS: Our review of 28 patient hospital records identified four patients who met the inclusion criteria. All four patients had active synovitis before starting treatment with TCZ. Successful TCZ therapy allowed them to plan to become pregnant. When pregnancy was confirmed, TCZ was terminated as soon as possible in all patients. Three patients delivered full-term infants without any adverse outcomes. One patient had a partial molar pregnancy and miscarried during gestational week 11. Two patients remained in clinical remission with low-dose prednisolone (PSL) or no treatment for RA during pregnancy. CONCLUSIONS: TCZ may be a good alternative therapy for RA patients with symptoms that are hard to control with TNF blockers who desire to bear children. PMID- 26872427 TI - AGEs trigger autophagy in diabetic skin tissues and fibroblasts. AB - OBJECTIVE: Accumulation of advanced glycation end products (AGEs) contributes to the development of diabetic ulcers. Recent evidence indicates that AGEs administration enhanced autophagy in many cell types. As a positive trigger of autophagy, the effect of AGEs on autophagy in skin tissues and fibroblasts remains unknown. METHODS: Skin tissues were isolated from Spreqne-Dawley rats and immunohistochemical staining was performed to analyze the location of LC3 and FOXO1 in skin tissues. Then primary cultured foreskin fibroblast cells with treated with AGEs and the effect of AGEs on autophagy was investigated. Protein level expressions of LC3, Beclin-1 and FOXO1 in fibroblasts were analyzed by Western blotting. Autophagic flux is detected with autophagy inhibitor chloroquine and mRFP-GFP-LC3 tandem construct. RESULTS: Compared with skin from normal rats, immunohistochemical staining shows a predominant LC3 localization in fibroblasts cytoplasm in diabetic rats. Elevated expression of FOXO1 also existed in diabetic rats dermis fibroblasts when compared with normal rats in immunohistochemical analysis. In human skin fibroblasts cells, AGEs administration stimulated the autophagy related LC3-II/LC3-I and Beclin-1 expressions and increased autophagy flux. In mRFP-GFP-LC3 puncta formation assays, both autolysosome and autophagosome were increased in human fibroblasts after treatment with AGEs. Fibroblasts exposed to AGEs also have increased FOXO1 expression compared with control group. CONCLUSION: AGEs could induce autophagy at least in part via regulating the FOXO1 activity in diabetic skin tissues and fibroblasts. PMID- 26872428 TI - MiR-26b inhibits melanoma cell proliferation and enhances apoptosis by suppressing TRAF5-mediated MAPK activation. AB - Alterations in microRNA-26b (miR-26b) expression have been shown to participate in various malignant tumor developments. However, the possible function of miR 26b in human melanoma cells remains unclarified. In this study, quantitative polymerase chain reaction was used to explore the expression profiles of miR-26b in melanoma cells. The effect of miR-26b on cell viability was determined by using MTT assays and colony formation assay. The apoptosis levels were evaluated by using Annexin V/fluorescein isothiocyanate (FITC) apoptosis detection kit and the apoptosis cells were confirmed by Transmission Electron Microscopy (TEM). Luciferase reporter plasmids were constructed to confirm direct targeting. Our study found that the expression of miR-26b was downregulated in human melanoma specimens. Overexpression of miR-26b significantly increased the anti proliferative effects and apoptosis in A375 and B16F10 melanoma cells. In addition, luciferase gene reporter assays confirmed that TRAF5 was a direct target gene of miR-26b and the anti-tumor effect of miR-26b in melanoma cells was significantly counteracted by treatment with TRAF5 overexpression. Furthermore, the molecular mechanisms underlying the tumor suppressor of miR-26b in malignant melanomas may be due to the dephosphorylation of MAPK pathway caused by the decrease in TRAF5 expression when miR-26b is up-regulated in melanoma cells. These findings indicate that miR-26b might influence TRAF5-MAPK signaling pathways to facilitate the malignant progression of melanoma cells. PMID- 26872430 TI - Classification of ADAMTS binding sites: The first step toward selective ADAMTS7 inhibitors. AB - Genome-wide association studies identified ADAMTS7 as a risk locus for coronary artery disease. In carotid arteries of rats, neointima formation after balloon mediated injury goes along with enhanced Adamts7 expression. Vice versa, Adamts7 deficient mice display reduced neointima formation following vascular injury. Although a causal link between ADAMTS7 and coronary artery disease remains to be proven, inhibition of ADAMTS7 represents a potential new target for intervention in this disease. ADAMTS7, a member of the 'a disintegrin and metalloproteinase with thrombospondin motifs' (ADAMTS) family of proteins, contains a catalytic zinc ion in the binding site of its metalloproteinase domain. The structure of ADAMTS7 and its inhibitors are unknown. In this study, we used in silico methods, including homology modeling and pharmacophore modeling, to analyze the ADAMTS7 metalloproteinase domain, particularly its binding site. The results revealed structural and sequence differences relative to the binding sites of the other ADAMTS proteins; these non-conserved regions represent potential binding regions for selective ADAMTS7 inhibitors. The main contribution of this study is the proposal of a pharmacophore for ADAMTS7. The characterization of the ADAMTS7 binding site and definition of a pharmacophore are the first step toward developing a new therapeutic target for coronary artery disease. PMID- 26872429 TI - Reduced DPP4 activity improves insulin signaling in primary human adipocytes. AB - DPP4 is a ubiquitously expressed cell surface protease which is also released to the circulation as soluble DPP4 (sDPP4). Recently, we identified DPP4 as a novel adipokine oversecreted in obesity and thus potentially linking obesity to the metabolic syndrome. Furthermore, sDPP4 impairs insulin signaling in an autocrine and paracrine fashion in different cell types. However, it is still unknown which functional role DPP4 might play in adipocytes. Therefore, primary human adipocytes were treated with a specific DPP4 siRNA. Adipocyte differentiation was not affected by DPP4 silencing. Interestingly, DPP4 reduction improved insulin responsiveness of adipocytes at the level of insulin receptor, proteinkinase B (Akt) and Akt substrate of 160 kDa. To investigate whether the observed effects could be attributed to the enzymatic activity of DPP4, human adipocytes were treated with the DPP4 inhibitors sitagliptin and saxagliptin. Our data show that insulin-stimulated activation of Akt is augmented by DPP4 inhibitor treatment. Based on our previous observation that sDPP4 induces insulin resistance in adipocytes, and that adipose DPP4 levels are higher in obese insulin-resistant patients, we now suggest that the abundance of DPP4 might be a regulator of adipocyte insulin signaling. PMID- 26872432 TI - Transoral laser microsurgery for locally advanced (T3-T4a) supraglottic squamous cell carcinoma: Sixteen years of experience. AB - BACKGROUND: Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). METHODS: We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. RESULTS: One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy free survival with preserved function was 74.5%. CONCLUSION: TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016. PMID- 26872433 TI - [Irritable bowel syndrome: New pathophysiological hypotheses and practical issues]. AB - In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. PMID- 26872431 TI - Acute pancreatitis as a complication of childhood cancer treatment. AB - Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children. PMID- 26872434 TI - [Cardiac arrhythmias: Diagnosis and management]. AB - Cardiac arrhythmias, with, on top of the list, atrial fibrillation, are frequent conditions and any physician might have to get involved at any stage of patient care (from diagnosis to treatment), without always having the opportunity to immediately refer to the cardiologist. The aim of this review is to present a summary of pathophysiology, clinical and electrocardiographic presentations, as well as diagnostic and therapeutic strategies for the main cardiac arrhythmias. Supra-ventricular tachycardias (atrial fibrillation and flutter, atrioventricular reciprocating tachycardias) and ventricular tachycardias will be consecutively presented and discussed. PMID- 26872436 TI - Corrigendum. PMID- 26872435 TI - Serum pentraxin-3 and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) predict severity of infections in acute decompensated cirrhotic patients. AB - BACKGROUND: Pentraxin-3 (PTX3) and soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) are new candidate prognostic markers for comorbidities and mortality in various inflammatory diseases. Acute decompensation of cirrhosis is characterized by acute exacerbation of chronic systemic inflammation. Recently, increased circulating PTX3 levels have been reported in nonalcoholic steatohepatitis patients and positively correlated with disease severity. This study aims to explore serum PTX3/sTWEAK levels and their relationship with clinical outcomes in cirrhotic patients with acute decompensation. METHODS: We analyzed serum PTX3/sTWEAK levels in relation to inhospital and 3-month new clinical events and survivals in cirrhotic patients with acute decompensation. RESULTS: During admission, serum PTX3/sTWEAK levels were significantly higher in acute decompensated cirrhotic patients than controls and positively correlated with protein-energy wasting (PEW), new infections, long hospital stays, high medical costs, and high mortality. During a 3-month follow up, acute decompensated cirrhotic patients with high serum PTX3/sTWEAK levels had more episodes of unplanned readmission and high 3-month mortality. On multivariate analysis, high PTX3/sTWEAK levels and PEW were independent risk factors for high mortality. CONCLUSION: High serum PTX3/sTWEAK levels and PEW are common in cirrhotic patients with acute decompensation. As compared with low serum PTX3 and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. Therefore, high serum PTX3/sTWEAK levels on hospital admission predict disease severity and case fatality in cirrhotic patients with acute decompensation. PMID- 26872438 TI - Palliative care of bone pain due to skeletal metastases: Exploring newer avenues using neutron activated (45)Ca. AB - INTRODUCTION: With an objective to develop a cost-effective radiochemical formulation for palliation of pain due to skeletal metastases, we have demonstrated a viable method for large-scale production of (45)Ca (t1/2=163 days, Ebetamax=0.3MeV) using moderate flux research reactor, its purification from radionuclidic impurities adopting electrochemical approach and preclinical evaluation of (45)CaCl2. METHODS: Irradiation parameters were optimized by theoretical calculations for production of (45)Ca with highest possible specific activity along with minimum radionuclidic impurity burden. Based on this, the radioisotope was produced in reactor by irradiation of isotopically enriched (98% in (44)Ca) CaO target at a thermal neutron flux of ~1 * 10(14) n.cm(-2).s(-1) for 4 months. Scandium-46 impurity co-produced along with (45)Ca was efficiently removed adopting an electrochemical separation approach. The bone specificity of (45)CaCl2 was established by in vitro studies involving its uptake in hydroxyapatite (HA) particles and also evaluating its biodistribution pattern over a period of 2 weeks after in vivo administration in Wistar rats. RESULTS: Thermal neutron irradiation of 100mg of enriched (98% in (44)Ca) CaO target followed by radiochemical processing and electrochemical purification procedure yielded ~37 GBq of (45)Ca with a specific activity of ~370 MBq/mg and radionuclidic purity>99.99%. The reliability and reproducibility of this approach were amply demonstrated by process demonstration in several batches. In vitro studies indicated significant uptake of (45)CaCl2 (up to 65%) in HA particles. In vivo biodistribution studies in Wistar rats showed specific skeletal accumulation (40-46%ID) with good retention over a period of 2 weeks. CONCLUSIONS: To the best of our knowledge, this is the first study on utilization of (45)CaCl2 in the context of nuclear medicine. The results obtained in this study hold promise and warrant further investigations for future translation of (45)CaCl2 to the clinics, thereby potentially enabling a cost-effective approach for metastatic bone pain palliation especially in developing countries. PMID- 26872439 TI - Novel (188)Re multi-functional bone-seeking compounds: Synthesis, biological and radiotoxic effects in metastatic breast cancer cells. AB - INTRODUCTION: Radiolabeled bisphosphonates (BPs) have been used for bone imaging and delivery of beta(-) emitting radionuclides for bone pain palliation. As a beta(-) emitter, (188)Re has been considered particularly promising for bone metastases therapy. Aimed at finding innovative bone-seeking agents for systemic radiotherapy of bone metastases, we describe herein novel organometallic compounds of the type fac-[(188)Re(CO)3(k(3)-L)], (L=BP-containing chelator), their in vitro and in vivo stability, and their cellular damage in MDAMB231 cells, a metastatic breast cancer cell line. METHODS: After synthesis and characterization of the novel organometallic compounds of the type fac [(188)Re(CO)3(k(3)-L)] their radiochemical purity and in vitro stability was assessed by HPLC. In vivo stability and pharmacokinetic profile were evaluated in mice and the radiocytotoxic activity and DNA damage were assessed by MTT assay and by the cytokinesis-block micronucleus (CBMN) assay, respectively. RESULTS: Among all complexes, (188)Re3 was obtained with high radiochemical purity (>95%) and high specific activity and presented high in vitro and in vivo stability. Biodistribution studies of (188)Re3 in Balb/c mice showed fast blood clearance, high bone uptake (16.1 +/- 3.3% IA/g organ, 1h p.i.) and high bone-to-blood and bone-to-muscle radioactivity ratios, indicating that it is able to deliver radiation to bone in a very selective way. The radiocytotoxic effect elicited by (188)Re3 in the MDAMB231 cells was dependent on its concentration, and was higher than that induced by identical concentrations of [(188)ReO4](-). Additionally, (188)Re3 elicited morphological changes in the cells and induced DNA damage by the increased number of MN observed. CONCLUSION: Altogether, our results demonstrate that (188)Re3 could be considered an attractive candidate for further preclinical evaluation for systemic radionuclide therapy of bone metastases considering its ability to deliver radiation to bone in a very selective way and to induce radiation damage. PMID- 26872437 TI - Kinetics modeling and occupancy studies of a novel C-11 PET tracer for VAChT in nonhuman primates. AB - INTRODUCTION: Deficits in cholinergic function have been found in the aged brain and in neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). The vesicular acetylcholine transporter (VAChT) is a reliable biomarker for the cholinergic system. We previously reported the initial in vitro and ex vivo characterization of (-)-[(11)C]TZ659 as a VAChT specific ligand. Here, we report the in vivo specificity, tracer kinetics, and dose occupancy studies in the nonhuman primate brain. METHODS: MicroPET brain imaging of (-)-[(11)C]TZ659 was performed under baseline conditions in two male macaques. Tracer kinetic modeling was carried out using a two-tissue compartment model (2TCM) and Logan plot with arterial blood input function and using a simplified reference tissue model (SRTM) and Logan plot (LoganREF) without blood input. Specificity for VAChT was demonstrated by pretreatment with (+)-pentazocine, (-) vesamicol, or S-(-)-eticlopride. Target occupancy (Occ) was calculated following pretreatment with escalating doses of (-)-vesamicol. RESULTS: Baseline PET imaging revealed selective retention in the striatum with rapid clearance from the cerebellar hemispheres as a reference region. Total volume of distribution (VT) values derived from both 2TCM and Logan analysis with blood input revealed ~3-fold higher levels of (-)-[(11)C]TZ659 in the striatum than the cerebellar hemispheres. Injection of (-)-vesamicol either as a blocking or displacing agent significantly reduced striatal uptake of (-)-[(11)C]TZ659. In contrast, pretreatment with the sigma-1 ligand (+)-pentazocine had no impact. Pretreatment with the S-(-)-eticlopride, a dopamine D2-like receptor antagonist, increased striatal uptake of (-)-[(11)C]TZ659. Striatal binding potential (BPND, range of 0.33-1.6 with cerebellar hemispheres as the reference region) showed good correlation (r(2)=0.97) between SRTM and LoganREF. Occupancy studies found that ~0.0057 mg/kg of (-)-vesamicol produced 50% VAChT occupancy in the striatum. CONCLUSION: (-)-[(11)C]TZ659 demonstrated specific and reversible VAChT binding and favorable pharmacokinetic properties for assessing the density of VAChT in the living brain. PMID- 26872440 TI - PET imaging of dopamine transporters with [(18)F]FE-PE2I: Effects of anti Parkinsonian drugs. AB - PURPOSE: This study aimed to assess the striatal [(18)F]FE-PE2I binding and the immunohistochemical stain of tyrosine hydroxylase (TH) in the striatum, and to evaluate the effects of therapeutic drugs on [(18)F]FE-PE2I binding. METHODS: Dynamic PET/CT of [(18)F]FE-PE2I was performed in Parkinson's disease (PD) rat models, induced by the unilateral injection of 6-OHDA into the striatum. A simplified reference tissue model method was used to calculate the striatal binding potential (striatal BPND). Each of the four normal rats was pretreated with pramipexole, amantadine, and escitalopram 30 min before [(18)F]FE-PE2I injection. The effect of L-DOPA combined with benserazide was assessed in the normal and PD rats. RESULTS: The BPND was significantly lower in the lesioned striatum than in the striatum of the normal rats. After the pretreatment with pramipexole, amantadine, and escitalopram, the values of the striatal BPND did not differ from those of the controls. The pretreatment with L-DOPA/benserazide, however, significantly reduced the striatal BPND. The striatal BPND of the PD rats with L-DOPA/benserazide pretreatment was not different from that of the same PD rats with placebo treatment. CONCLUSION: [(18)F]FE-PE2I may be used as a radioligand for the in-vivo imaging of the DAT. In the normal rats, [(18)F]FE PE2I binding is unaffected by pramipexole, amantadine, and escitalopram. L DOPA/benserazide does not affect the striatal [(18)F]FE-PE2I binding in PD rats. PMID- 26872441 TI - Kit formulation for preparation and biological evaluation of a novel (99m)Tc-oxo complex with metronidazole xanthate for imaging tumor hypoxia. AB - INTRODUCTION: Achieving an ideal (99m)Tc labeled nitroimidazole hypoxia marker is still considered to be of great interest. Metronidazole xanthate (MNXT) ligand was synthesized and radiolabeled with (99m)Tc-glucoheptonate (GH) to form the (99m)TcO-MNXT complex, for the potential use as a novel probe for imaging tumor hypoxia. METHODS: For labeling, (99m)TcO-MNXT was prepared by ligand-exchange reaction with (99m)Tc-GH. The radiochemical purity of the (99m)TcO-MNXT complex was measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The distribution coefficient and stability of the complex was investigated. The structure of the (99m)TcO-MNXT complex was verified by preparation and characterization of the corresponding stable rhenium complex. The cellular uptake of the (99m)TcO-MNXT complex was determined in murine sarcoma S180 cell lines under hypoxic and aerobic conditions. The biodistribution and single photon emission computed tomography (SPECT) image studies of the (99m)TcO MNXT complex were performed in mice bearing S 180 tumor. RESULTS: The radiochemical purity of the (99m)TcO-MNXT complex was over 90%. It had good in vitro stability and its distribution coefficient indicated that it was a hydrophilic complex. When (99m)Tc and Re complexes were coinjected in HPLC, both radioactivity (for (99m)Tc complex) and UV detectors (for Re complex) showed nearly identical HPLC profiles, suggesting their structures are similar. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the (99m)TcO-MNXT complex had a good hypoxic selectivity and accumulated in the tumor with high uptake and good retention. Single photon emission computed tomography (SPECT) image studies showed that the tumor detection was observable. CONCLUSIONS: (99m)TcO-MNXT is prepared from a kit without the need for purification and shows high tumor uptake, tumor/blood and tumor/muscle ratios, suggesting that it would be a promising candidate for imaging tumor hypoxia. PMID- 26872442 TI - Noninvasive visualization of microRNA-155 in multiple kinds of tumors using a radiolabeled anti-miRNA oligonucleotide. AB - PURPOSE: We investigated whether a (99m)Tc radiolabeled anti-miRNA-155 oligonucleotide (AMO-155) could visualize the expression of miR-155 in multiple kinds of tumors in vivo. METHODS: AMO-155 was chemically synthesized and modified with 2'-O-methyl (2'-OMe) and phosphorothioate (PS). It was radiolabeled with (99m)Tc via the conjugation with NHS-MAG3 at 5' end. The characterization of radiolabeling and serum stability was evaluated using high performance liquid chromatography (HPLC) and agarose gel electrophoresis. The expression of C/EBPbeta, one of the miR-155 target proteins, was assessed using Western blot. The cellular uptake and delivery of AMO-155 was further evaluated in tumor cells. (99m)Tc-AMO-155 was tested in vivo in multiple tumor models, including miR-155 over-expressed and low-expressed tumor models. Finally, biodistribution of (99m)Tc-AMO-155 was evaluated. RESULTS: (99m)Tc-AMO-155 was prepared with high yield and radiochemical purity. It showed high stability in fresh human serum for 10h. (99m)Tc-AMO-155 displayed comparable capacity as unlabeled AMO-155 to increase the expression of C/EBPbeta protein in MCF-7 cells. (99m)Tc-AMO-155 showed an increased radioactive uptake in MCF-7 cells after 8h of incubation, whereas no change of (99m)Tc-pertechnetate uptake was observed. Carboxyfluorescein (FAM) labeled AMO-155 had higher fluorescent delivery than Control in HeLa and HepG2 cells by confocal microscopy. In miR-155 over-expressed tumor models, (99m)Tc-AMO-155 showed significantly higher tumor accumulation than (99m)Tc-Control. Furthermore, (99m)Tc-AMO-155 was capable of discriminating between MCF-7 and MDA-MB-231 tumors based on their expression of miR-155. CONCLUSIONS: Our study successfully prepared and proved (99m)Tc-AMO-155 as a prospective imaging agent for the noninvasive visualization of miR-155 expression in vivo. PMID- 26872443 TI - Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models. AB - OBJECTIVES: The aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy. METHODS: Galactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, (68)Ga, and injected (i.v., 45-95 MUCi, 1.5 pmol/g TBW) into 44 healthy, 19 DEN-, and 22 CDAA-treated male rats. Quantification of liver function was achieved by calculating T90, defined as the time for the liver to accumulate 90 percent of the [(68)Ga]GSA plateau value. All livers were excised immediately after imaging and prepared for a "blinded" histologic examination, which included fibrosis and fat content scores. Two sets of fibrosis scores were recorded for all of animals. The dominant fibrosis stage was recorded as the "Dominant Pattern" score and the "Maximum Pattern" score was assigned if a smaller distinct region with a higher fibrosis score was observed. RESULTS: Animals with Dominant Pattern F0-F1 liver fibrosis (D(-)=39) demonstrated significantly (P<0.0001) faster accumulation of [(68)Ga]GSA (2.40 +/- 0.52 min) than those with moderate to advanced Dominant Pattern fibrosis F2 and F4 (D(+)=26) (3.48 +/- 1.01 min). ROC analysis (F0-F1 vs F2-F4) produced an area under the binormal curve (AUC) of 0.867 +/- 0.045. Twenty seven of the 65 rats had small regions with higher fibrosis scores. Six of these Maximum Pattern scores reclassified the animals from D(-) to D(+). ROC analysis of F0-F1 versus F2-F4 rats without liver fat produced AUCs of 0.881 +/- 0.053 for the Dominant Pattern Score and 0.944 +/- 0.035 for the Maximum Pattern Score. CONCLUSIONS: PET Functional Imaging of [(68)Ga]GSA accurately discriminates early from moderate experimental fibrosis independent of steatosis grade. If validated in human studies, molecular imaging may emerge as a potential alternative to invasive liver biopsy. PMID- 26872444 TI - Is timolol an effective treatment for pyogenic granuloma? AB - BACKGROUND: Pyogenic granuloma (PG) is a benign vascular tumor that can be treated by cautery (chemical or thermal), laser, excision, curettage, sclerotherapy, and cryotherapy. Topical timolol is emerging as a non-invasive modality for the treatment of PGs. METHODS: We recruited a series of 10 patients with PG, who received treatment with 0.5% timolol maleate ophthalmic solution applied 4 times a day, 2 drops per dose. No other medication, topical or systemic, was given. Pulse rate, blood pressure, and blood glucose were monitored at baseline and weekly thereafter for the duration of treatment. ECG was done at baseline. The efficacy of the treatment was evaluated by considering a complete response, a partial response, and no response. RESULTS: Of 10 patients, four showed complete response within 3-24 days, with no recurrence at 3-month follow up. Three patients each showed partial or no response. No local or systemic side effects were reported in any of the patients. CONCLUSIONS: The response of PGs to beta blockers seems to be variable. Although topical timolol has the advantage of minimal adverse events, ease of administration, and better cosmetic outcomes, it's efficacy in PG may not be universal unlike in infantile hemangiomas. Topical timolol may be a treatment option in young children, incapacitated elderly, and over delicate areas like face, nails, and gums where invasive modalities are not desirable. PMID- 26872445 TI - Relationships between risky sexual behaviour, dysexecutive problems, and mental health in the years following interdisciplinary TBI rehabilitation. AB - Little is known about the long-term consequences of traumatic brain injury (TBI) regarding risky sexual behaviour. The objectives of the study were (1) to compare risky sexual behaviour in a sample of individuals with TBI having received interdisciplinary rehabilitation with that of healthy controls, and (2) to explore the relationships between risky sexual behaviour, executive functions, and mental health in individuals with TBI. The study group consisted of 42 individuals with TBI with a mean age of 37.9 years (SD = 9.7), 12.8 years of education (SD = 3.3), and 3.3 years post-injury (SD = 4.3). Healthy controls consisted of 47 participants, with a mean age of 37.6 years (SD = 10.7), and 13 years of education (SD = 3). Risky sexual behaviour was measured with the Sexual Risk Survey and executive function with the Dysexecutive Questionnaire. Mental health measures included the Generalised Anxiety Disorder Scale, and the Patient Health Questionnaire for depression. Compared to healthy controls, individuals with TBI reported more dysexecutive and mental health problems, without differences in risky sexual behaviour. In individuals with TBI, risky sexual behaviour was associated with behavioural, cognitive and emotional dysexecutive problems, but not with anxiety or depression. It was concluded that special attention should be given to individuals with TBI showing difficulties in executive functions given their association with risky sexual behaviour. PMID- 26872446 TI - Endograft repair for pseudoaneurysms and penetrating ulcers of the ascending aorta. AB - OBJECTIVE: The aim of this paper is to report midterm results of thoracic endovascular aortic repair (TEVAR) for ascending aortic pseudoaneurysms (AAPs) and penetrating aortic ulcers (PAUs) of the ascending aorta. METHODS: This study was retrospective and performed at tertiary centers. Eight patients with AAPs (n = 5) and PAUs (n = 3) received total endovascular repair of the ascending aorta. Patients with a history of type A aortic dissection or fusiform aneurysm were excluded. All patients analyzed were considered to be at high risk for open repair at the time of presentation. RESULTS: Urgent intervention was performed in 6 (75%) cases. Primary clinical success was achieved in 7 (87.5%) cases. A low flow type 3 endoleak remained asymptomatic and was managed conservatively. No TEVAR-related in-hospital mortality, primary conversion, cerebrovascular accidents, valve impairment, or myocardial infarction occurred. All patients were discharged home, alive and independent, after a median length of stay of 6 (range: 5-24) days. No patient was lost at a mean follow-up of 40 +/- 33 (range: 4-93) months. Ongoing primary clinical success was maintained in all but 1 patient (type 3 endoleak): aortically related reintervention was never required. No endograft breakage or migration was observed. At 1-year follow-up, 7 (87.5%) aortic lesions had significant reduction in diameter (>=5 mm). CONCLUSIONS: Ascending TEVAR was feasible, safe, and effective for AAPs and PAUs. In a very select subset of lesions, midterm results were favorable, with both standard and custom-designed endografts. PMID- 26872447 TI - Is there a role for postinduction positron emission tomography and computed tomography with fludeoxyglucose F 18? A call for standardization. PMID- 26872448 TI - Caught between a rock and a hard place: Venous thromboembolism screening in high risk patients. PMID- 26872449 TI - Improving operating room efficiency--A value proposition. PMID- 26872450 TI - Attitudes towards the Faecal Occult Blood Test (FOBT) versus the Faecal Immunochemical Test (FIT) for colorectal cancer screening: perceived ease of completion and disgust. AB - BACKGROUND: Colorectal cancer screening is key to early detection and thus to early treatment, but uptake is often sub-optimal, particularly amongst lower income groups. It is proposed that the imminent introduction of the single-sample Faecal Immunochemical Test (FIT) in Scotland may lead to increased uptake as compared to the current Faecal Occult Blood Test (FOBT), but underlying reasons are yet to be determined. The aim was to evaluate attitudes and intentions towards completing the FIT compared to the current FOBT for colorectal cancer screening. METHODS: A convenience sample of 200 adults (mean age 56.5, range 40 89; 59% female) living in Scotland rated both the FOBT and the FIT with regard to ease of completion, perceived disgust and intention to complete and return (all measured on Likert-type 1-7 scale). Participants were randomised to be presented (via a face-to-face contact) with either the FIT or FOBT first. RESULTS: Participants reported higher intention to complete and return the FIT versus the FOBT (mean difference 0.62, 95% CI (0.44, 0.79)). Overall, 85.0% (n = 170) of participants agreed or strongly agreed that they would intend to complete and return the FIT compared to 65.5% (n = 131) for the FOBT (chi(2) = 20.4, p < .001). The FIT was also perceived to be easier to complete (mean difference 0.85, 95% CI (0.70, 1.01) and much less disgusting (mean difference 1.11, 95% CI (0.94, 1.27)). Lower perceived disgust, higher socio-economic status and previous participation in any cancer screening were significant predictors of intention to complete the FOBT, whilst only higher perceived ease of completion predicted intention to complete the FIT. CONCLUSIONS: People reported higher intentions to complete and return a FIT than a FOBT test for colorectal cancer screening, largely due to a perception that it is easier and less disgusting to complete. The findings suggest that the introduction of the FIT as standard in the UK could result in a notable increase in screening uptake. PMID- 26872451 TI - Identification of blood meal sources in the main African malaria mosquito vector by MALDI-TOF MS. AB - BACKGROUND: The identification of blood meal sources in malaria vectors is critical to better understanding host/vector interactions and malaria epidemiology and control. Currently, the identification of mosquito blood meal origins is based on time-consuming and costly techniques such as precipitin tests, ELISA and molecular tools. Although these tools have been validated to identify the blood meal and trophic preferences of female Anopheles mosquitoes, they present several limitations. Recently, matrix-assisted, laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successfully used as a quick and accurate tool for arthropod identification, including mosquitoes. The aim of the present work was to test whether MALDI-TOF MS could also be applied to identification of blood meal sources from engorged mosquitoes. METHODS: Abdomen proteins extracted from Anopheles gambiae (stricto sensu, S molecular form) that were either unengorged or artificially engorged on seven distinct types of vertebrate blood (human, horse, sheep, rabbit, mouse, rat, dog) were submitted for MALDI-TOF MS. RESULTS: The comparison of mass spectrometry (MS) spectra from mosquito abdomens collected 1 h post-feeding, were able to discriminate blood meal origins. Moreover, using Aedes albopictus specimens, abdominal protein MS spectra from engorged mosquitoes were found specific to host blood source and independent of the mosquito species. A sequential analysis revealed stability of mosquito abdominal protein spectra up to 24 h post-feeding. CONCLUSIONS: These results indicate that MALDI-TOF MS could determine feeding patterns of freshly engorged mosquitoes up to 24 h post-blood meal. The MALDI-TOF MS technique appears to be an efficient tool for large epidemiological surveillance of vector-borne diseases and outbreak source identification. PMID- 26872453 TI - Evaluation of a modified knee rotation angle in MRI scans with and without trochlear dysplasia: a parameter independent of knee size and trochlear morphology. AB - PURPOSE: Regarding TT-TG in knee realignment surgery, two aspects have to be considered: first, there might be flaws in using absolute values for TT-TG, ignoring the knee size of the individual. Second, in high-grade trochlear dysplasia with a dome-shaped trochlea, measurement of TT-TG has proven to lack precision and reliability. The purpose of this examination was to establish a knee rotation angle, independent of the size of the individual knee and unaffected by a dysplastic trochlea. METHODS: A total of 114 consecutive MRI scans of knee joints were analysed by two observers, retrospectively. Of these, 59 were obtained from patients with trochlear dysplasia, and another 55 were obtained from patients presenting with a different pathology of the knee joint. Trochlear dysplasia was classified into low grade and high grade. TT-TG was measured according to the method described by Schoettle et al. In addition, a modified knee rotation angle was assessed. Interobserver reliability of the knee rotation angle and its correlation with TT-TG was calculated. RESULTS: The knee rotation angle showed good correlation with TT-TG in the readings of observer 1 and observer 2. Interobserver correlation of the parameter showed excellent values for the scans with normal trochlea, low-grade and high-grade trochlear dysplasia, respectively. All calculations were statistically significant (p < 0.05). CONCLUSION: The knee rotation angle might meet the requirements for precise diagnostics in knee realignment surgery. Unlike TT-TG, this parameter seems not to be affected by a dysplastic trochlea. In addition, the dimensionless parameter is independent of the knee size of the individual. LEVEL OF EVIDENCE: II. PMID- 26872454 TI - Management of patellar problems in skeletally mature patients with nail-patella syndrome. AB - PURPOSE: Nail-patella syndrome (NPS) or hereditary onychoosteodysplasia is a rare autosomal dominant disease, characterized by a tetrad of findings, which include fingernail abnormalities, hypoplasia of the patellae, radial head dislocation and prominent iliac horns. Most of the literature on the treatment of patellar problems in NPS concerns paediatric patients, and there is no standard treatment algorithm for adult patients. METHODS: We reviewed the charts of skeletally mature patients with NPS who presented to our clinic. We reviewed the presenting complaints, the physical examination findings and the radiographic imaging. RESULTS: We identified seven skeletally mature patients with NPS who presented with patellofemoral complaints. Their symptoms were instability, pain, or a combination of the two. Examination and imaging revealed a wide range of severity but included patellar instability and patellar arthritis. In our series, milder forms of the disease were treated with non-operative measures, but the majority of our patients required surgery including medial patellofemoral ligament reconstruction, tibial tuberosity transposition, patellofemoral and total knee arthroplasty. At midterm follow-up, most patients had good results. CONCLUSION: Nail-patella syndrome has a wide range of presentations and severity in skeletally mature patients. Knee surgeons should be familiar with the spectrum of clinical presentation and the range of treatment options available in order to provide optimum treatment for patients with this disorder. LEVEL OF EVIDENCE: IV. PMID- 26872455 TI - Lanostane Triterpenoids from Fruiting Bodies of Ganoderma leucocontextum. AB - Six new lanostane-type triterpenoids, namely leucocontextins S-X (1-6), together with twelve known compounds, were isolated from the fruiting bodies of Ganoderma leucocontextum. Their structures were established by MS and NMR data. PMID- 26872456 TI - The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia. AB - While the specific trigger of Parkinson Disease (PD) in most patients is unknown, considerable evidence suggests that the neuroinflammatory response makes an essential contribution to the neurodegenerative process. Drugs targeting metabotropic glutamate receptors (mGlu receptors), 7 Transmembrane (7TM) spanning/G protein coupled receptors that bind glutamate, are emerging as therapeutic targets for PD and may have anti-inflammatory properties. ADX88178 is novel potent, selective, and brain-penetrant positive allosteric modulator of the mGlu4 which is under evaluation for treatment of PD and other neurological disorders. We used microglia cultured from mouse brain to determine if ADX88178 had direct effects on the inflammatory responses of these cells. We studied both microglia from wild type and Grm4 knock out mice. We found that activation of mGlu4 with ADX88178 attenuated LPS-induced inflammation in primary microglia, leading to a decrease in the expression of TNFalpha, MHCII, and iNOS, markers of pro-inflammatory responses. These effects were absent in microglia from mice lacking mGlu4. These results demonstrate a cell-autonomous anti-inflammatory effect of ADX88178 mediated mGlu4 activation on microglia, and suggest that this drug or similar activators or potentiators of mGlu4 may have disease-modifying as well as symptomatic effects in PD and other brain disorders with an inflammatory component. PMID- 26872458 TI - Osteoblastic Actions of the Neuropeptide Y System to Regulate Bone and Energy Homeostasis. AB - Neural pathways are now a well-appreciated factor in the regulatory milieu controlling the maintenance of bone mass. A number of neural pathways from the brain to bone have been identified. These pathways often involve elements of the energy homeostatic apparatus, indicating links between the regulation of bone metabolism and energy balance. Neuropeptide Y is one such factor that co regulates these two processes. Initial studies outlined the skeletal actions of NPY from within the brain and the interactions with energy homeostatic processes. However, in recent years, an appreciation for the actions of NPY within bone cells has expanded. Cells of the osteoblastic lineage express both NPY ligand and a cognate receptor NPY, Y1R. Murine studies have demonstrated that both ligand and receptor actively control bone mass and osteoblast activity and interact with mechanical signals to integrate with the local loading environment. Local NPY signalling regulates osteoprogenitor production and differentiation, to cover the entire osteoblastic lineage. In addition, several recent studies have demonstrated extra-skeletal actions of osteoblastic NPY signalling, to regulate energy expenditure and with it adiposity, and in a separate study, to control release of a factor-controlling beta cell mass and insulin production/release and with it glucose tolerance. Thus, osteoblastic neuropeptide production and signalling illustrates the rapidly widening sphere of influence of skeletal tissue, and suggests a far more complex and interconnected physiology then is currently appreciated. PMID- 26872459 TI - Hydroxychloroquine hindering of diabetic isletopathy carries its signature on the inflammatory cytokines. AB - Hydroxychloroquine (HCQ) is supposed to have favorable effects in diabetes mellitus (DM). However no previous experimental studies had investigated its effect on the structure of the endocrine pancreas, islets of Langerhans (IOL), in DM. In addition, the mechanism by which HCQ acts in DM is not well understood. In this study, we hypothesized that the possible favorable effects of HCQ in DM at the structural as well as at metabolic levels could be accomplished, in part, by its anti-inflammatory action. A total of 45 rats were divided equally into; control, DM and HCQ + DM groups (received citrate buffer, 27.5 mg/kg single ip STZ and STZ + HCQ 200 mg/kg/w respectively). After 4 weeks, samples from pancreas were histologically studied for the resulting changes. The HCQ + DM group showed preservation of IOL structure, a significant increase (p < 0.05) in the beta-cell area, %, mass, IOL proliferation and neogenesis as well as correction of the significantly increased (p < 0.05) alpha-cell area, %, disturbed glucose homeostasis and lipid profile compared with the DM group. The significantly elevated inflammatory cytokines in the latter were lowered in the HCQ + DM group. Therefore, HCQ showed definite favorable effects on the histological as well as the metabolic profiles in DM which may be partly attributed to its anti inflammatory action. This notable improvement of DM by HCQ deserves further studies to distinctly approve HCQ as a promising oral hypoglycemic agent. PMID- 26872460 TI - Arboviruses and apoptosis: the role of cell death in determining vector competence. AB - A relatively small number of mosquito species transmit arboviruses such as dengue, yellow fever, chikungunya and West Nile viruses to hundreds of millions of people each year, yet we still lack a thorough understanding of the molecular factors that determine vector competence. Apoptosis has been shown to be an important factor in determining the outcome of virus infection for many viruses. However, until recently, it was not clear whether apoptosis plays a role in determining the outcome of arbovirus infections in mosquitoes. Recent work has begun to shed light on the roles of apoptosis in this important process. PMID- 26872461 TI - NHS "winter" pressure could become norm in summer, experts warn. PMID- 26872457 TI - Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio. AB - Quitting smoking significantly reduces the risk of tobacco-related morbidity and mortality, yet there is a high rate of relapse amongst smokers who try to quit. Phenotypic biomarkers have the potential to improve smoking cessation outcomes by identifying the best available treatment for an individual smoker. In this review, we introduce the nicotine metabolite ratio (NMR) as a reliable and stable phenotypic measure of nicotine metabolism that can guide smoking cessation treatment among smokers who wish to quit. We address how the NMR accounts for sources of variation in nicotine metabolism including genotype and other biological and environmental factors such as estrogen levels, alcohol use, body mass index, or menthol exposure. Then, we highlight clinical trials that validate the NMR as a biomarker to predict therapeutic response to different pharmacotherapies for smoking cessation. Current evidence supports the use of nicotine replacement therapy for slow metabolizers, and non-nicotine treatments such as varenicline for normal metabolizers. Finally, we discuss future research directions to elucidate mechanisms underlying NMR associations with treatment response, and facilitate the implementation of the NMR as biomarker in clinical practice to guide smoking cessation. PMID- 26872462 TI - Effector function of CTLs is increased by irradiated colorectal tumor cells that modulate OX-40L and 4-1BBL and is reversed following dual blockade. AB - BACKGROUND: Sub-lethal doses of ionizing radiation (IR) can alter the phenotype of target tissue by modulating genes that influence effector T cell activity. Previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor associated antigens (TAA). However, there is limited information available regarding how T cells themselves are altered following these interactions with irradiated tumor cells. METHODS: Here, several human colorectal tumor cell lines were exposed to radiation (0-10 Gy) in vitro and changes in the expression of molecules costimulatory to effector T cells (4-1BBL, OX-40L, CD70, ICOSL) were examined by flow cytometry. T cell effector function was assessed to determine if changes in these proteins were directly related to the changes in T cell function. RESULTS: We found OX-40L and 4-1BBL to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-IR while ICOSL and CD70 remained largely unaltered. Expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by TAA-specific T-cells. Importantly, blocking of both OX-40L and 4-1BBL reversed radiation enhanced T-cell killing of human tumor targets as well as T-cell survival and activation. CONCLUSIONS: Overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector T cell activity. PMID- 26872463 TI - Idiopathic Toe Walking: Tests and Family Predisposition. AB - The aim of this study is to provide clinical examination methods that were designed specifically to assess the level of severity among children with idiopathic toe walking (ITW). The idiopathic toe-walking pattern of 836 children was recorded and analyzed during 4 years. Questionnaires and clinical measurements were evaluated, along with differential tests, assessing the occurrence and severity of toe walking. Questions about family history and onset of toe walking were evaluated along with special tests and measurements assessing the occurrence and severity of toe walking. The different measurements apply during this study, ankle dorsiflexion, lumbar lordosis angle, as well as the clinical spin test, walking after spin test, and heel walking test revealed in all cases that children with a positive family predisposition were significantly more affected than children with negative family predisposition. It is concluded that children with ITW and a positive family predisposition were more intensively affected during all performed clinical tests than children with no family predisposition. The tests used during this study have not being used by any other researches, even though they showed significant differences between the children with ITW and children with a normal gait pattern. LEVELS OF EVIDENCE: Diagnostic, Level II: development of diagnostic test with consecutive patients and control patients. PMID- 26872464 TI - Pediatric spinal arteriovenous malformations and fistulas: a single institute's experience. AB - OBJECTIVE: Pediatric spinal vascular diseases are extremely rare. We aimed to evaluate their clinical characteristics and treatment outcomes in our institute. DESIGN: A total of 10 patient files were retrospectively reviewed, including 3 cases of intramedullary arteriovenous malformations (AVMs), 6 cases of perimedullary arteriovenous fistulas (AVFs), and 1 case of epidural AVF. Clinical features, radiological findings, treatment results, and clinical outcomes were evaluated. The median durations of the radiologic and clinical follow-ups were 17.7 and 107.9 months, respectively. RESULTS: The male to female ratio was 1:1, with a median age at diagnosis of 9 years. All AVMs were juvenile type, all perimedullary AVFs were high flow types (three type IVb and three type IVc), and one epidural AVF was associated with intradural venous drainage. Most cases (90 %) were located in the cervical spine and conus medullaris. Acute neurological deterioration was identified in five patients; however, bleeding was identified in only one patient. Two cases were surgically treated, seven cases underwent embolization, and one case underwent radiosurgery. Three cases were completely obliterated, and their clinical states were improved (n = 2; 66.7 %) and stationary (n = 1; 33.3 %). Meanwhile, seven cases were incompletely obliterated, and their clinical states were improved (n = 2; 28.6 %), stationary (n = 3; 42.8 %), and aggravated (n = 2; 28.6 %). CONCLUSIONS: Pediatric spinal AVMs and AVFs were mostly complex and high flow types, and complete obliteration could not be satisfactorily achieved. Incompletely treated lesions should be closely followed up because they may worsen. PMID- 26872465 TI - Sacral agenesis: evaluation of accompanying pathologies in 38 cases, with analysis of long-term outcomes. AB - PURPOSE: Sacral agenesis (SA), or caudal regression syndrome, is a congenital malformation of the spine of varying degree of severity. The aim of our study was to identify associated impairments in structure and function of the orthopedic, neurological, cardiopulmonary, genitourinary, and gastrointestinal systems, and to evaluate their impact on function. METHODS: This was a retrospective case series analysis of 38 patients with SA. Patients were divided into two groups: SA with myelomeningocele (group 1) and without myelomeningocele (group 2). Between group comparisons in terms of the features of the SA, impairments in associated systems, impact on gross motor function, need for surgery, and association with prenatal screening and maternal gestational diabetes were evaluated. RESULTS: The majority of comorbidities were orthopedic and neurological in nature. Impairments in sphincter control and independent transferring were more prevalent in group 1, resulting in lower function. Scoliosis, kyphosis, and hip dislocation/subluxation were the most common orthopedic problems, with a higher prevalence of kyphosis in group 1. The requirement for neurosurgery was significantly higher in group 1. CONCLUSIONS: Orthopedic and neurological comorbidities are commonly associated with SA and are more prevalent in the presence of a myelomeningocele. As the impairments impact a child's ability for maximum function, early identification and intervention is required to correct or ameliorate the impairment. LEVEL OF EVIDENCE: Level IV. PMID- 26872466 TI - Temperature-dependent development and the significance for estimating postmortem interval of Chrysomya nigripes Aubertin, a new forensically important species in China. AB - In forensic entomology, the developmental duration and larval body length of sarcosaprophagous flies are presently the two major approaches to estimate minimal postmortem interval (PMImin). A full characterization of the developmental stages of Calliphoridae, a predominating species on corpses, is especially important for PMI estimation. Chrysomya nigripes Aubertin, which appears on the corpse mainly during the decay and the post-decay stages, is of significant value for PMImin estimation. However, there are limited detailed reports on the development of such species. Hence, this study was conducted to address the development pattern of C. nigripes, in order to provide the basic data related to PMI estimation. In this study, the larvae of C. nigripes were collected from pig carcasses that were placed in the field. The colonies were cultured at constant temperatures of 16, 20, 24, 28, and 32 (+/-1) degrees C. The biological features of C. nigripes, the developmental pattern, and the body length with time at different temperatures were studied. The results showed that the average developmental duration of the C. nigripes larvae at 20, 24, 28, and 32 (+/-1) degrees C were 608.0 +/- 68.0 h, 327.0 +/- 53.8 h, 254.0 +/- 36.5 h, and 217.0 +/- 28.0 h, respectively. There were two phases of body length increment with developmental time: growing phase and plateau phase. The maximal body length was 11-12 mm, and the relationship between body length and developmental time can be simulated using the following equation: L = a + bT + cT(2) + dT(3). The data for developmental duration and larval body length at 16 degrees C were not obtained. In summary, this study comprehensively studied the developmental biology of C. nigripes, which has a significant value for estimating PMI from highly decayed carcasses. PMID- 26872468 TI - Do multiple temperature measurements improve temperature-based death time estimation? The information degradation inequality. AB - The accuracy of the input parameter values limits the accuracy of the output values in forensic temperature-based death time estimation (TDE) like in many scientific methods. A standard strategy to overcome this problem is to perform multiple measurements of the input parameter values, but such approaches are subject to noise accumulation and stochastic dependencies. A quantitative mathematical analysis of advantages as well as disadvantages of multiple measurements approaches (MMAs) was performed. The results are A general stochastic model of MMA. The information degradation inequality quantifying gains and losses of MMAs. Example calculations of the information degradation inequality for the following two MMAs relevant to TDE: o Multiple successive rectal temperature measurements o Multiple synchronous body layer temperature measurements Neither multiple successive rectal temperature measurements nor multiple synchronous body layer temperature measurements seem to significantly improve death time estimation. MMAs are superior to the single measurement approach only in the very early body cooling phase. PMID- 26872469 TI - Post-mortem 1.5T MR quantification of regular anatomical brain structures. AB - Recently, post-mortem MR quantification has been introduced to the field of post mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging. PMID- 26872471 TI - Additive antiangiogenesis effect of ginsenoside Rg3 with low-dose metronomic temozolomide on rat glioma cells both in vivo and in vitro. AB - BACKGROUND: Glioblastoma is the most common and deadly primary brain tumor in adults. Low-dose,metronomic (LDM) temozolomide (TMZ) displays improved efficacy in the treatment of glioblastoma by targeting angiogenesis, but has a limited effect on recurrence. The antiangiogenesis drug ginsenoside Rg3 (RG3) is the main active ingredient of ginseng, a popular herbal medicine. METHODS: Using an in vitro and a rat model of an orthotopic glioma allograft, this study was to determine whether RG3 enhanced the antiangiogenesis activity of LDM TMZ in the treatment of glioblastoma. RESULTS: Our results showed that combined use of TMZ with RG3 displayed additive inhibition on proliferation of both human umbilical vein endothelial cells (HUVEC) and rat C6 glioma cells in vitro. They additively arrested cell cycle, increased apoptosis, and decreased VEGF-A and BCL-2 expression in HUVEC. Antiangiogenesis effect was also evaluated in the rat model of orthotopic glioma allograft, based upon markers including relative cerebral blood volume (rCBV) by magnetic resonance imaging (MRI), VEGF levels and microvessel density (MVD)/CD34 staining. LDM TMZ alone was potent in suppressing angiogenesis and tumor growth, whereas RG3 alone only had modest antiangiogenesis effects. Combined treatment significantly and additively suppressed angiogenesis, without additive inhibitory effects on allografted tumor growth. CONCLUSIONS: These data provide evidence showing the efficacy of LDM TMZ on glioma treatment. The combined additive antiangiogenesis effect suggests that RG3 has the potential to further increase the efficacy of LDM TMZ in the treatment of glioblastoma. PMID- 26872470 TI - Sudden infant death syndrome caused by cardiac arrhythmias: only a matter of genes encoding ion channels? AB - Sudden infant death syndrome is the unexpected demise of a child younger than 1 year of age which remains unexplained after a complete autopsy investigation. Usually, it occurs during sleep, in males, and during the first 12 weeks of life. The pathophysiological mechanism underlying the death is unknown, and the lethal episode is considered multifactorial. However, in cases without a conclusive post mortem diagnosis, suspicious of cardiac arrhythmias may also be considered as a cause of death, especially in families suffering from any cardiac disease associated with sudden cardiac death. Here, we review current understanding of sudden infant death, focusing on genetic causes leading to lethal cardiac arrhythmias, considering both genes encoding ion channels as well as structural proteins due to recent association of channelopathies and desmosomal genes. We support a comprehensive analysis of all genes associated with sudden cardiac death in families suffering of infant death. It allows the identification of the most plausible cause of death but also of family members at risk, providing cardiologists with essential data to adopt therapeutic preventive measures in families affected with this lethal entity. PMID- 26872474 TI - Why diverticulosis haunts the Western world. PMID- 26872472 TI - Measurements of Chlorpyrifos Levels in Forager Bees and Comparison with Levels that Disrupt Honey Bee Odor-Mediated Learning Under Laboratory Conditions. AB - Chlorpyrifos is an organophosphate pesticide used around the world to protect food crops against insects and mites. Despite guidelines for chlorpyrifos usage, including precautions to protect beneficial insects, such as honeybees from spray drift, this pesticide has been detected in bees in various countries, indicating that exposure still occurs. Here, we examined chlorpyrifos levels in bees collected from 17 locations in Otago, New Zealand, and compared doses of this pesticide that cause sub-lethal effects on learning performance under laboratory conditions with amounts of chlorpyrifos detected in the bees in the field. The pesticide was detected at 17 % of the sites sampled and in 12 % of the colonies examined. Amounts detected ranged from 35 to 286 pg.bee(-1), far below the LD50 of ~100 ng.bee(-1). We detected no adverse effect of chlorpyrifos on aversive learning, but the formation and retrieval of appetitive olfactory memories was severely affected. Chlorpyrifos fed to bees in amounts several orders of magnitude lower than the LD50, and also lower than levels detected in bees, was found to slow appetitive learning and reduce the specificity of memory recall. As learning and memory play a central role in the behavioral ecology and communication of foraging bees, chlorpyrifos, even in sublethal doses, may threaten the success and survival of this important insect pollinator. PMID- 26872475 TI - Women's Behavioral Responses to the Threat of a Hypothetical Date Rape Stimulus: A Qualitative Analysis. AB - One in four college women experience sexual assault on campus; yet, campuses rarely provide the in-depth self-defense programs needed to reduce sexual assault risk. Further, little is known about the range of possible behaviors elicited by sexual assault threat stimuli besides assertion. To fill this gap, the aim of the current study was to explore qualitative themes in women's intended behavioral responses to a hypothetical sexual assault threat, date rape, by using a laboratory-controlled threat. College women (N = 139) were randomly assigned to one of four different levels of sexual assault threat presented via an audio recorded vignette. Participants articulated how they would hypothetically respond to the experimentally assigned threat. Responses were blinded and analyzed using Consensual Qualitative Research methodology. Six major themes emerged: assertion, compliance/acceptance, conditional decision making, avoidance, expressions of discomfort, and allusion to future contact. Although almost all participants described assertion, a number of non-assertive responses were described that are not currently recognized in the literature. These non-assertive responses, including compliance/acceptance, conditional decision making, and avoidance, may represent unique behavioral response styles and likely reflect the complex psychological process of behavioral response to threat. The variety of themes found illustrates the great range of behavioral responses to threat. This broad range is not currently well represented or measured in the literature and better understanding of these responses can inform future interventions, advocacy efforts, and policies focused on sexual assault. PMID- 26872477 TI - Associations Among Excess Weight Status and Tobacco, Alcohol, and Illicit Drug Use in a Large National Sample of Early Adolescent Youth. AB - Adolescent substance use and overweight/obesity each are public health priorities, with unique prevalences based on race/ethnicity. Whether these biobehavioral risks are linked in today's youth is unknown, leaving critical gaps in prevention science. Utilizing a national epidemiological sample of 10th grade students (N = 19,678; M age = 16.09 years; 69.5 % White, 14.5 % Black, 16.0 % Hispanic; 2008-2009 Monitoring the Future), we examined adolescent substance use behaviors (current use, grade of first use, polysubstance use) for adolescents of overweight (OV), obese (OB), or severely obese (SO) status compared to adolescents of healthy weight (HW) for each race/ethnicity group. We also examined how engagement in smoking behaviors (current, early grade at first use) was linked to other substance use behaviors for youth of varying degrees of excess weight. Relative to HW youth, White youth of excess weight, particularly SO, had higher odds of early (< grade 9) substance use and use of some illicit substances (inhalants, cocaine, amphetamines) within the past year. Among White early smokers, OB and SO had higher odds of other substance use, whereas White OB and SO recent smokers had lower odds of other substance use. Few significant findings based on weight status were identified for Black or Hispanic youth. These findings suggest adolescent health risk behaviors co-occur uniquely for White youth, in particular those who are SO and by early adolescence. Understanding the downstream public health consequences and how risk pathways of excess weight, tobacco, and other substance use may uniquely unfold for each race/ethnicity group is imperative. PMID- 26872478 TI - Evaluation of the Environmental Supports Scale with a Community Sample of Adolescents. AB - Environmental sources of psychosocial support have been found to modulate or protect against the development of psychopathology and risk behavior among adolescents. Capturing sources of environmental support across multiple developmental contexts requires the availability of well-validated, concise assessments-of which there are few in the existing literature. In order to address this need, the current study explored the factor structure, concurrent and convergent validity of the Environmental Supports Scale (ESS; Genetic, Social, and General Psychology Monographs, 117; 395-417, 1991) with a community sample of adolescents. An unconstrained exploratory factor analysis revealed a separate factor for home, school, and neighborhood settings. Internal consistency and test-retest reliability were evaluated for each factor. Concurrent and predictive validity analyses revealed that the ESS was associated in the expected directions across a range of constructs relevant to adolescent development including internalizing symptoms, well-being, external influences, and engagement in risk behavior. Convergent validity for the neighborhood context was established with an assessment of neighborhood environmental adversity. A brief assessment of perceived environmental support across key developmental contexts provides an important tool for research on resilience processes during adolescence and may help illuminate key protective factors and inform intervention and prevention efforts. PMID- 26872479 TI - Understanding and Measuring Coach-Teacher Alliance: A Glimpse Inside the 'Black Box'. AB - Coaching models are increasingly used in schools to enhance fidelity and effectiveness of evidence-based interventions; yet, little is known about the relationship between the coach and teacher (i.e., coach-teacher alliance), which may indirectly enhance teacher and student outcomes through improved implementation quality. There is also limited research on measures of coach teacher alliance, further hindering the field from understanding the active components for successful coaching. The current study examined the factor structure and psychometric characteristics of a measure of coach-teacher alliance as reported by both teachers and coaches and explored the extent to which teachers and coaches reliably rate their alliance. Data come from a sample of 147 teachers who received implementation support from one of four coaches; both the teacher and the coach completed an alliance questionnaire. Separate confirmatory factor analyses for each informant revealed four factors (relationship, process, investment, and perceived benefits) as well as an additional coach-rated factor (perceived teacher barriers). A series of analyses, including cross-rater correlations, intraclass correlation coefficients, and Kuder-Richardson reliability estimates suggested that teachers and coaches provide reliable, though not redundant, information about the alliance. Implications for future research and the utilization of the parallel coach-teacher alliance measures to increase the effectiveness of coaching are discussed. PMID- 26872476 TI - It is a matter of timing: asynchrony during pollen development and its consequences on pollen performance in angiosperms-a review. AB - Functional pollen is needed to successfully complete fertilization. Pollen is formed inside the anthers following a specific sequence of developmental stages, from microsporocyte meiosis to pollen release, that concerns microsporocytes/microspores and anther wall tissues. The processes involved may not be synchronous within a flower, an anther, and even a microsporangium. Asynchrony has been barely analyzed, and its biological consequences have not been yet assessed. In this review, different processes of pollen development and lifetime, stressing on the possible consequences of their differential timing on pollen performance, are summarized. Development is usually synchronized until microsporocyte meiosis I (occasionally until meiosis II). Afterwards, a period of mostly asynchronous events extends up to anther opening as regards: (1) meiosis II (sometimes); (2) microspore vacuolization and later reduction of vacuoles; (3) amylogenesis, amylolysis, and carbohydrate inter-conversion; (4) the first haploid mitosis; and (5) intine formation. Asynchrony would promote metabolic differences among developing microspores and therefore physiologically heterogeneous pollen grains within a single microsporangium. Asynchrony would increase the effect of competition for resources during development and pollen tube growth and also for water during (re)hydration on the stigma. The differences generated by developmental asynchronies may have an adaptive role since more efficient pollen grains would be selected with regard to homeostasis, desiccation tolerance, resilience, speed of (re)hydration, and germination. The performance of each pollen grain which landed onto the stigma will be the result of a series of selective steps determined by its development, physiological state at maturity, and successive environmental constrains. PMID- 26872480 TI - Traversing the folding pathway of proteins using temperature-aided cascade molecular dynamics with conformation-dependent charges. AB - Protein folding is a multi-micro second time scale event and involves many conformational transitions. Crucial conformational transitions responsible for biological functions of biomolecules are difficult to capture using current state of-the-art molecular dynamics (MD) simulations. Protein folding, being a stochastic process, witnesses these transitions as rare events. Many new methodologies have been proposed for observing these rare events. In this work, a temperature-aided cascade MD is proposed as a technique for studying the conformational transitions. Folding studies for Engrailed homeodomain and Immunoglobulin domain B of protein A have been carried out. Using this methodology, the unfolded structures with RMSD of 20 A were folded to a structure with RMSD of 2 A. Three sets of cascade MD runs were carried out using implicit solvation, explicit solvation, and charge updation scheme. In the charge updation scheme, charges based on the conformation obtained are calculated and are updated in the topology file. In all the simulations, the structure of 2 A was reached within a few nanoseconds using these methods. Umbrella sampling has been performed using snapshots from the temperature-aided cascade MD simulation trajectory to build an entire conformational transition pathway. The advantage of the method is that the possible pathways for a particular reaction can be explored within a short duration of simulation time and the disadvantage is that the knowledge of the start and end state is required. The charge updation scheme adds the polarization effects in the force fields. This improves the electrostatic interaction among the atoms, which may help the protein to fold faster. PMID- 26872481 TI - TRPV1 channel as a target for cancer therapy using CNT-based drug delivery systems. AB - Carbon nanotubes are being considered for the design of drug delivery systems (DDSs) due to their capacity to internalize molecules and control their release. However, for cellular uptake of drugs, this approach requires an active translocation pathway or a channel to transport the drug into the cell. To address this issue, it is suggested to use TRPV1 ion channels as a potential target for drug release by nano-DDSs since these channels are overexpressed in cancer cells and allow the permeation of large cationic molecules. Considering these facts, this work presents three studies using molecular dynamics simulations of a human TRPV1 (hTRPV1) channel built here. The purpose of these simulations is to study the interaction between a single-wall carbon nanotube (SWCNT) and hTRPV1, and the diffusion of doxorubicin (DOX) across hTRPV1 and across a POPC lipid membrane. The first study shows an attractive potential between the SWCNT surface and hTRPV1, tilting the adsorbed SWCNT. The second study shows low diffusion probability of DOX across the open hTRPV1 due to a high free energy barrier. Although, the potential energy between DOX and hTRPV1 reveals an attractive interaction while DOX is inside hTRPV1. These results suggest that if the channel is dilated, then DOX diffusion could occur. The third study shows a lower free energy barrier for DOX across the lipid membrane than for DOX across hTRPV1. Taking into account the results obtained, it is feasible to design novel nano-DDSs based on SWCNTs to accomplish controlled drug release into cells using as translocation pathway, the hTRPV1 ion channel. PMID- 26872482 TI - Boundary conditions for free A-DNA in solution and the relation of local to global DNA structures at reduced water activity. AB - Because of repeated claims that A-DNA cannot exist without aggregation or condensation, the state of DNA restriction fragments with 84-859 bp has been analyzed in aqueous solutions upon reduction of the water activity. Rotational diffusion times tau (d) measured by electric dichroism at different water activities with a wide variation of viscosities are normalized to values tau (c) at the viscosity of water, which indicate DNA structures at a high sensitivity. For short helices (chain lengths [Formula: see text] <= persistence length p), cooperative formation of A-DNA is reflected by the expected reduction of the hydrodynamic length; the transition to the A-form is without aggregation or condensation upon addition of ethanol at monovalent salt <=1 mM. The aggregation boundary, indicated by a strong increase of tau (c), is shifted to higher monovalent salt (>=4 mM) when ethanol is replaced by trifluoroethanol. The BA transition is not indicated anymore by a cooperative change of tau (c) for [Formula: see text] " p; tau (c) values for these long chains decrease upon reduction of the water activity continuously over the full range, including the BA transition interval. This suggests a non-cooperative BC transition, which induces DNA curvature. The resulting wide distribution of global structures hides changes of local length during the BA transition. Free A-DNA without aggregation/condensation is found at low-salt concentrations where aggregation is inhibited and/or very slow. In an intermediate range of solvent conditions, where the A-form starts to aggregate, a time window remains that can be used for analysis of free A-DNA in a quasi-equilibrium state. PMID- 26872485 TI - Incontinence and psychological problems in children: a common central nervous pathway? AB - Nocturnal enuresis is caused by a mismatch between the nocturnal bladder capacity and the nocturnal diuresis rate, in the presence of a deficient arousability in the majority of patients, according to the pediatric and urologic literature. Psychiatric and psychologic literature are still concentrating on the potential role of psychological factors and central nervous mechanisms in the pathogenesis, as is reflected in the DMS-5 criteria. However, research has clearly shown several important comorbidities between neuropsychological dysfunctions and nocturnal enuresis. Due to the increased comorbidity of (neuro)psychological problems, sleep problems, circadian rhythms, and enuresis, the question arises as to whether there is a possible common central pathway in the pathogenesis. It is likely that the coexistence of these problems can be attributed to a common central nervous system involvement. The specific role of the central nervous system remains unclear, but several pathways are possible. The high comorbidity between enuresis, sleep, and (neuro)psychological functioning is probably attributable to a common pathogenetic pathway, emphasizing the importance of a multidisciplinary focus in screening and treatment in children with nocturnal enuresis. PMID- 26872483 TI - From juvenile hyperuricaemia to dysfunctional uromodulin: an ongoing metamorphosis. AB - Familial juvenile hyperuricaemic nephropathy (FJHN) is a diagnosis that is easily missed. It has taken a long time to clarify the pathophysiology and prevalence of this disease entity which has been shown to be genetically identical to medullary cystic kidney disease (MCKD) type II. The initial suspicion that uric acid was the noxious agent has been replaced by the recognition that a mutant uromodulin (UMOD) is the real culprit-although the exact mechanisms of pathogenicity remain uncertain. The mutation has been traced to the UMOD gene in chromosome 16. The disease is characterised by the classic triad of autosomal dominant inheritance, progressive renal failure beginning in the third to fifth decade of life and gout. Phenotypically similar but genotypically distinct entities have been described over the last 10 years, making a clinical diagnosis difficult. These include mutations in the renin, hepatocyte nuclear factor 1-beta and mucin 1 genes. UMOD-associated kidney disease has been proposed as a logical diagnostic label to replace FJHN, but given all these other mutations, an over-arching diagnostic term of 'autosomal dominant tubulointerstitial kidney disease' (ADTKD) has been recently adopted. Allopurinol has been suggested as a therapeutic agent, but unfortunately this was based on non-randomised uncontrolled trials with small patient numbers. PMID- 26872484 TI - Role of hypoxia during nephrogenesis. AB - Mammals develop in a physiologically hypoxic state, and the oxygen tension of different tissues in the embryo is precisely controlled. Deviation from normal oxygenation, such as what occurs in placental insufficiency, can disrupt fetal development. Several studies demonstrate that intrauterine hypoxia has a negative effect on kidney development. As nascent nephrons are forming from nephron progenitors in the nephrogenic zone, they are exposed to varying oxygen tension by virtue of the development of the renal vasculature. Thus, nephrogenesis may be linked to oxygen tension. However, the mechanism(s) by which this occurs remains unclear. This review focuses on what is known about molecular mechanisms active in physiological and pathological hypoxia and their effects on kidney development. PMID- 26872486 TI - New York City flavoured tobacco product sales ban evaluation. AB - INTRODUCTION: The availability of flavoured tobacco products is associated with increased initiation and youth smoking. New York City prohibited all sales of flavoured cigars, cigarillos, little cigars, chew, snuff, snus, tobacco, pipe tobacco, roll-your-own tobacco, and dissolvables, excluding menthol, in October 2009; enforcement began in November 2010. This paper describes the sales ban evaluation. METHODS: Data on retail tobacco sales of cigars, smokeless and other tobacco products such as pipe tobacco and roll-your-own, were analysed using interrupted time series methods, estimating changes in flavoured and non flavoured tobacco product inflation-adjusted dollar sales overall, and by product type. Changes in ever use of flavoured tobacco products, any tobacco product use, and smoking prevalence among adolescents were estimated using multivariable logistic regression. RESULTS: Sales of flavoured tobacco products declined overall (87%; p<0.001), and for flavoured cigars (86%; p<0.001) and flavoured pipe and roll-your-own (91%; p<0.001) following ban enforcement, while non flavoured sales increased for cigars (5%; p=0.003) and pipe and roll-your-own (4%, p=0.030). In adjusted models, teens in 2013 had 37% lower odds of ever trying flavoured tobacco products (p<0.001), 28% lower odds of using any type of tobacco product (p=0.025), and a non-significant change in current smoking prevalence (p=0.114) compared with teens in 2010. CONCLUSIONS: Flavoured tobacco product sales and odds of ever using flavoured tobacco products or using any tobacco products among teens declined significantly after ban enforcement began. Collectively these findings demonstrate significant evidence that the flavoured tobacco products sales ban was successful in New York City, and could succeed elsewhere. PMID- 26872487 TI - Heat effects among migrant and seasonal farmworkers: a case study in Colorado. AB - BACKGROUND: Although migrant and seasonal farmworkers are highly vulnerable to ambient heat because of their working conditions, heat effects in this population have been rarely studied. OBJECTIVES: We estimated effects of heat on mean daily counts of clinic visits among migrant and seasonal farmworkers by taking advantage of a unique longitudinal medical records database in the USA. METHODS: We compiled a daily weather and clinic visit data set based on data from a health centre in Colorado for the summer of 2013. A total of 14 481 patients were included in our analysis, including 150 migrant farmworkers and 231 seasonal farmworkers with an average of 3 and 4 visits per day. We used Poisson regression to estimate the associations between heat and daily all-cause or cardiovascular specific clinic visits among migrant or seasonal farmworkers or other stratified patients. We defined heat effects as the percentage difference in average daily counts of clinic visits, comparing 90-50th centiles of daily mean apparent temperature, a composite index accounting for both temperature and humidity. We conducted a sensitivity analysis to evaluate the impact of adjustment for ozone levels and different heat definitions. RESULTS: Estimates of heat effects on average daily clinic visits among migrant farmworkers were positive (88.0%, 95% CI: 26.2% to 180.0%). We did not observe statistically significant associations between heat and clinic visits among other stratified groups. CONCLUSIONS: Our study appears to be the first to link heat effects with clinic data among migrant and seasonal farmworkers. This research suggests possible significant impact of heat on migrant farmworkers and provides justifications for further studies. PMID- 26872488 TI - Inorganic Phosphate Activates the AKT/mTORC1 Pathway and Shortens the Life Span of an alpha-Klotho-Deficient Model. AB - Inorganic phosphate (Pi) has been implicated in the pathogenesis of accelerated aging; however, the underlying mechanisms remain elusive. Herein, we demonstrated in cultured cells and in vivo that increased levels of extracellular Pi activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway by suppressing membrane-bound phosphatase and tensin homolog (PTEN) levels in a manner requiring the sodium-dependent Pi transporter PiT-1. High levels of extracellular Pi also led to phosphorylation of Ser/Thr clusters in the C-terminal tail of PTEN, which has been shown to dissociate PTEN from the membrane. Notably, blockade of mTORC1 activity by rapamycin treatment prolonged the life span of hyperphosphatemic alpha-Klotho-deficient (Kl(-/-)) mice. Dietary correction of hyperphosphatemia or treatment with rapamycin also rescued the brown adipose tissue dysfunction and oxidative damage observed in Kl(-/-) mice. Furthermore, rapamycin treatment partially rescued these effects and extended the life span when Kl(-/-) mice were maintained on a high-phosphate diet. Finally, rapamycin reduced circulating Pi levels in Kl(-/-) mice, apparently by decreasing the localization of sodium dependent Pi transport protein 2a at the renal brush border membrane. Therefore, the activation of mTORC1 may create a vicious loop that exacerbates the retention of Pi, which in turn may enhance oxidative damage and ultimately shorten the life span of Kl(-/-) mice. These results demonstrate that Pi has important roles in the aging process, and the blockade of mTORC1 may have therapeutic potential for premature aging-like symptoms associated with hyperphosphatemia. PMID- 26872491 TI - Can selection on a male mating character result in evolutionary change? A selection experiment on California wild radish, Raphanus sativus. AB - PREMISE OF THE STUDY: Whenever more pollen grains arrive on stigmas than necessary to fertilize ovules, sexual selection is possible. However, the role of sexual selection remains controversial, in part because of lack of evidence on genetic bases of traits and the response of relevant characters to selection. METHODS: In an experiment with Raphanus sativus, we selected on tendency to sire seeds in the stylar or basal regions of fruits. This character is likely related to pollen tube growth rate, and seed position affects rates of abortion and seed predation. We measured differences among families in seed siring and related characters and evaluated responses to selection. KEY RESULTS: All replicates showed strong effects of pollen donor family on proportion of seeds sired per fruit in mixed pollinations. Most also showed effects of pollen donor family on number of pollen grains per flower and pollen diameter. Two of four replicates showed a response to selection on position of seeds sired. In responding replicates, we found trade-offs in pollen grain size and number; plants with larger pollen grains sired more seeds in the basal region. CONCLUSIONS: Our data suggest a genetic basis for pollen donor ability to sire seeds in competition. The significant response to selection in two replicates shows that position of seeds sired can respond to selection. Thus, all components for sexual selection to occur and affect traits are present. Variation in results among replicates might be due to changes in greenhouse conditions. Environmental effects may contribute to the maintenance of variation in these fitness-related characters. PMID- 26872492 TI - Transient hybridization, not homoploid hybrid speciation, between ancient and deeply divergent conifers. AB - PREMISE OF THE STUDY: Homoploid hybrid speciation is receiving growing attention due the increasing recognition of its role in speciation. We investigate if individuals intermediate in morphology between the two species of the conifer genus Athrotaxis represent a homoploid hybrid species, A. laxifolia, or are spontaneous F1 hybrids. METHODS: A total of 1055 individuals of Athrotaxis cupressoides and A. selaginoides, morphologically intermediate individuals, and two putative hybrid swarms were sampled across the range of the genus and genotyped with 13 microsatellites. We used simulations to test the power of our data to identify the pure species, F1s, F2s, and backcross generations. KEY RESULTS: We found that Athrotaxis cupressoides and A. selaginoides are likely the most divergent congeneric conifers known, but the intermediates are F1 hybrids, sharing one allele each from A. cupressoides and A. selaginoides at six loci with completely species specific alleles. The hybrid swarms contain wide genetic variation with stronger affinities to the locally dominant species, A. selaginoides and A. selaginoides backcrosses outnumbering A. cupressoides backcrosses. In addition, we observed evidence for isolated advanced generation backcrosses within the range of the pure species. CONCLUSIONS: We conclude that, even though they can be large and long-lived, Athrotaxis hybrid swarms are on a trajectory of decline and will eventually be reabsorbed by the parental species. However, this process may take millennia and fossil evidence suggests that such events have occurred repeatedly since the early Quaternary. Given this timeline, our study highlights the many obstacles to homoploid hybrid speciation. PMID- 26872493 TI - Antibiotic resistance: the emergence of plasmid-mediated colistin resistance enhances the need of a proactive one-health approach. PMID- 26872489 TI - Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant. AB - The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor-specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor-specific antibody generation at the individual level. PMID- 26872494 TI - Acetone-butanol-ethanol fermentation of corn stover: current production methods, economic viability and commercial use. AB - Biobutanol is a next-generation liquid biofuel with properties akin to those of gasoline. There is a widespread effort to commercialize biobutanol production from agricultural residues, such as corn stover, which do not compete with human and animal foods. This pursuit is backed by extensive government mandates to expand alternative energy sources. This review provides an overview of research on biobutanol production using corn stover feedstock. Structural composition, pretreatment, sugar yield (following pretreatment and hydrolysis) and generation of lignocellulose-derived microbial inhibitory compounds (LDMICs) from corn stover are discussed. The review also discusses different Clostridium species and strains employed for biobutanol production from corn stover-derived sugars with respect to solvent yields, tolerance to LDMICs and in situ solvent recovery (integrated fermentation). Further, the economics of cellulosic biobutanol production are highlighted and compared to corn starch-derived ethanol and gasoline. As discussed herein, the economic competitiveness of biobutanol production from corn stover largely depends on feedstock processing and fermentation process design. PMID- 26872495 TI - Cadmium-induced cell killing in Sacharomyces cerevisiae involves increases in intracellular NO levels. AB - Cadmium is a widespread environmental pollutant and poses some potential risks to human health. However, the signaling events controlling cadmium toxicity are not fully understood. In this study, we examined the effect of cadmium chloride on cell viability and the intracellular nitric oxide (NO) level in yeast cells. The results showed that exposure of yeast cells to cadmium (0-100 MUM) could induce cell killing with significantly increased intracellular NO levels. Morphological analysis of the nuclei with 4('),6-diamidino-2-phenylindole staining and DNA strand breaks analysis showed that cadmium at 50 MUM can induce cell apoptosis in yeast cells. Treatment of yeast cells with cadmium (50 MUM) and the nitric oxide scavenger c-PTIO [2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-1-oxyl-3 oxide; 0.2 mM] showed that c-PTIO attenuated the cadmium-induced cell killing. Our findings indicated that cadmium-induced yeast cell killing is mediated by a directly increased intracellular NO level. PMID- 26872496 TI - Perception of occupational balance by people with mental illness: A new methodology. AB - Aims The aims were to (i) investigate initial construct validity of a tool for assessment of time allocation in occupational balance, and (ii) describe perceived occupational balance and its relationship with socio-demographics, well being, and personal recovery among people with mental illness. Methods Satisfaction with Daily Occupations and Occupational Balance (SDO-OB) was administered to 226 persons. SDO-OB reflects balance in five occupational domains: work, leisure, home chores, self-care, and overall occupational balance. Indicators for assessing construct validity were: satisfaction with everyday occupations, occupational value, symptom severity, and psychosocial functioning. For the second aim, the data collection included socio-demographics, life quality, self-esteem, self-mastery, and personal recovery. Results Occupational balance ratings indicated the participants were either under-occupied or in balance. Few were over-occupied. Feeling in balance was related to greater well being and recovery compared with being under-occupied. Risk factors for under occupation were younger age (in relation to work), and higher education (in relation to overall balance). Conclusions Associations with the indicators suggest initial construct validity. The SDO-OB is promising for assessment of occupational balance among people with mental illness. Being under-occupied was detrimental to well-being and recovery, and this indicates the importance of offering more occupational opportunities for people with mental illness. PMID- 26872497 TI - A case of neonatal lupus erythematosus in a very low-birth-weight infant that suffered intraventricular hemorrhage at birth. AB - This report describes the case of a very low-birth-weight male infant with neonatal lupus erythematosus. His mother had Sjogren's syndrome, and her previous child had suffered a complete heart block. Accordingly, maternal steroid (betamethasone) therapy was administered to prevent a congenital heart block for 15 weeks (from 13 to 27 weeks' gestation). At 28 weeks' gestation, the mother was weaned off the steroid therapy, and an emergency cesarean section was carried out at 29 weeks and 6 days' gestation because of a nonreassuring fetal status (NRFS). At birth, the infant exhibited grade-III intraventricular hemorrhage (IVH). Although it is unclear why the infant developed a NRFS and IVH, the condition of the fetus should be carefully monitored during and after long-term maternal steroid treatment. PMID- 26872498 TI - Cryopreserving turkey semen in straws and nitrogen vapour using DMSO or DMA: effects of cryoprotectant concentration, freezing rate and thawing rate on post thaw semen quality. AB - 1. This study was designed to identify a suitable protocol for freezing turkey semen in straws exposed to nitrogen vapour by examining the effects of dimethylacetamide (DMA) or dimethylsulfoxide (DMSO) as cryoprotectant (CPA), CPA concentration, freezing rate and thawing rate on in vitro post-thaw semen quality. 2. Pooled semen samples were diluted 1:1 (v:v) with a freezing extender composed of Tselutin diluent containing DMA or DMSO to give final concentrations of 8% or 18% DMA and 4% or 10% DMSO. The semen was packaged in 0.25 ml plastic straws and frozen at different heights above the liquid nitrogen (LN2) surface (1, 5 and 10 cm) for 10 min. Semen samples were thawed at 4 degrees C for 5 min or at 50 degrees C for 10 s. After thawing, sperm motility, viability and osmotic tolerance were determined. 3. Cryosurvival of turkey sperm was affected by DMSO concentration. Freezing rate affected the motility of sperm cryopreserved using both CPAs, while thawing rates showed an effect on the motility of sperm cryopreserved using DMA and on the viability of sperm cryopreserved using DMSO. Significant interactions between freezing rate * thawing rate on sperm viability in the DMA protocol were found. 4. The most effective freezing protocol was the use of 18% DMA or 10% DMSO with freezing 10 cm above the LN2 surface and a thawing temperature of 50 degrees C. An efficient protocol for turkey semen would improve prospects for sperm cryobanks and the commercial use of frozen turkey semen. PMID- 26872499 TI - Natural variation in the glucose content of dilute sulfuric acid-pretreated rice straw liquid hydrolysates: implications for bioethanol production. AB - Rice straw is a promising resource for bioethanol production. Because the glucose content of pretreatment liquid hydrolysates is highly correlated with ethanol yield, the selection of appropriate rice cultivars is essential. The glucose content in liquid hydrolysates of pretreated rice straws of 208 diverse cultivars was evaluated in natural field in 2013 and 2014 using a novel high-throughput system. The glucose content of the rice straw samples varied across cultivars and was affected by environmental factors such as temperature and solar radiation. Several high-quality cultivars exhibiting high glucose content in both years were identified. The results of this study can aid in development of novel rice cultivars suitable as both feedstocks for bioethanol production and cooking. PMID- 26872500 TI - Synthesis of a Series of gamma-Keto Allyl Phosphonates. AB - Under solvent-free conditions and at 80 degrees C, a DMAP- or imidazole-mediated clean and rapid conversion of cyclic Morita-Baylis-Hillman (MBH) acetates into the corresponding gamma-keto allyl phosphonates in 70-93% yields is described herein. This allylic nucleophilic substitution works well with primary and secondary acetates bearing, at the beta'-position, linear or branched alkyl groups and aryl groups. PMID- 26872501 TI - Feasibility and effectiveness of cognitive remediation in the treatment of borderline personality disorder. AB - Several studies have demonstrated that borderline personality disorder (BPD) is associated with neuropsychological deficits and there is evidence that the neurocognitive profile of patients with BPD may be related to the outcome of this disorder. The aim of this study was to investigate the feasibility and the effectiveness of a cognitive remediation intervention in patients with BPD. Thirty patients with a DSM-IV-TR diagnosis of BPD were assessed on clinical, neuropsychological and functional outcome measures at baseline and after 16 weeks of a computer-assisted cognitive remediation (CACR) intervention or treatment as usual (TAU). Patients who received CACR showed a greater improvement in working memory and psychosocial functioning measures than patients treated with TAU. Symptom severity was not significantly affected by CACR treatment. The findings of this pilot study suggest the feasibility and potential effectiveness on specific cognitive domains, but modest clinical usefulness of a computerised modality of cognitive remediation in the treatment of BPD. PMID- 26872502 TI - ACHA Guidelines. PMID- 26872503 TI - Development of an Innovative Treatment Paradigm for Intimate Partner Violence Victims With Depression and Pain Using Community-Based Participatory Research. AB - Intimate partner violence (IPV) is a public health issue with complex physical health, mental health and social consequences that can exacerbate survivors' barriers to health care engagement and support. Furthermore, health care professionals are often unaware of or feel ill-equipped to address survivors' complex needs. Depression and chronic pain are particularly prevalent co occurring problems for survivors and can impede engagement and outcomes in traditional health care. This study's purpose was to understand what interventions might be more responsive to survivors' myriad needs, particularlly those with depression and pain. Survivors were involved with the design, execution, analysis, and interpretation of results, based on community-based participatory research principles. Intervention development happened in two phases: the first consisted of focus groups with survivors to inform the intervention and the second included intervention design, informed by a community advisory board (CAB). Thirty-one survivors participated in Phase 1, and they reported preferring a range of support including formal help-seeking, informal coping strategies, and spirituality. In Phase 2, the CAB (comprised of survivors, health care professionals, and researchers) identified three distinct aspects of a comprehensive IPV intervention: (a) education regarding both the complex health issues and available local resources; (b) an integrated consultation service for providers to seek recommendations for responding to the full spectrum of survivors' needs; and (c) a trauma-informed, accessible clinic. Academic medical centers could not have designed this intervention in isolation; survivors and providers played an integral part of this process, and continue to inform our current work. PMID- 26872504 TI - Predicting Parent-Child Aggression Risk: Cognitive Factors and Their Interaction With Anger. AB - Several cognitive elements have previously been proposed to elevate risk for physical child abuse. To predict parent-child aggression risk, the current study evaluated the role of approval of parent-child aggression, perceptions of children as poorly behaved, and discipline attributions. Several dimensions of attributions specifically tied to parents' discipline practices were targeted. In addition, anger experienced during discipline episodes was considered a potential moderator of these cognitive processes. Using a largely multiple-indicator approach, a sample of 110 mothers reported on these cognitive and affective aspects that may occur when disciplining their children as well as responding to measures of parent-child aggression risk. Findings suggest that greater approval of parent-child aggression, negative perceptions of their child's behavior, and discipline attributions independently predicted parent-child aggression risk, with anger significantly interacting with mothers' perception of their child as more poorly behaved to exacerbate their parent-child aggression risk. Of the discipline attribution dimensions evaluated, mothers' sense of external locus of control and believing their child deserved their discipline were related to increase parent-child aggression risk. Future work is encouraged to comprehensively evaluate how cognitive and affective components contribute and interact to increase risk for parent-child aggression. PMID- 26872506 TI - Cyber Dating Abuse Victimization Among Secondary School Students From a Lifestyle Routine Activities Theory Perspective. AB - Controlling one's romantic partner through digital media is a form of cyber dating abuse. To design effective educational campaigns, a deeper understanding of how some young people become victim of this type of abuse within their romantic relationships is warranted. This study is the first to adopt a lifestyle routine activities theory perspective toward online romantic partner monitoring, by looking at whether secondary school students' risky digital lifestyle and their digital media use are linked to a higher chance of being controlled by a romantic partner, taking into account gender, age, and the length of the romantic relationship. The data of 466 secondary school students (71.0% girls, n = 331) between 16 and 22 years old ( M = 17.99 years; SD = 0.92) who were in a romantic relationship are analyzed. Linear regression analysis suggests that engagement in online risk behavior, the length of the romantic relationship, engagement in sexting with the romantic partner, and the amount of social networking site use were significantly linked to victimization of digital controlling behavior. The results are important to practitioners, as they indicate that messages about safe Internet use should be incorporated in prevention and educational campaigns with regard to cyber dating abuse. Suggestions for future research are discussed. PMID- 26872505 TI - Implementing Trauma and Grief Component Therapy for Adolescents and Think Trauma for Traumatized Youth in Secure Juvenile Justice Settings. AB - We describe a multiyear pilot dissemination of a trauma-focused group treatment, Trauma and Grief Component Therapy for Adolescents, coupled with a trauma informed staff training, Think Trauma, to six residential juvenile justice (JJ) facilities. All staff members were trained in Think Trauma. Seventy-seven youth from four facilities completed the treatment groups and 69 completed all pre- and postgroup assessment measures. The aims of this study were to determine whether trauma-focused interventions (a) could be implemented in complex JJ systems, (b) would be associated with a decrease in posttraumatic symptoms and reactions in youth, and (c) might contribute to reduced Incident Reports in facilities. A related question was whether we would receive feedback that youth who participated in the trauma and/or grief narrative components of the intervention were adversely affected. Pre- and postgroup assessments indicated significant reductions in symptoms of posttraumatic stress, depression, and anger, but not in anxiety or sexual concerns. There were significantly greater reductions in posttraumatic stress disorder (PTSD) among incarcerated youth who completed all modules of the group treatment intervention relative to incarcerated youth who received an abbreviated version. Two of the facilities tracked their Incident Reports and reported reductions. No Incident Reports or therapist feedback documented that the trauma/grief processing components of the intervention were destabilizing to the youth. PMID- 26872507 TI - A Longitudinal Examination of Mothers' Depression and PTSD Symptoms as Impacted by Partner-Abusive Men's Harm to Their Children. AB - Intimate partner violence (IPV) is a serious and widespread form of gender-based violence that disproportionately affects women. It is well established that IPV victimization contributes to depression and posttraumatic stress disorder (PTSD), and that many partner-abusive men continue to perpetuate abuse even after their relationship with the victim ends. In addition, when men harm their partners, they are more likely to harm their children, and evidence suggests that this harm continues post-separation. However, scant research has been conducted on men's harm to their children as an extension of IPV perpetration, with even less known about the mental health impact this form of abuse has on mothers. For this longitudinal cohort study, 40 partner-abused mothers who had separated, or were planning to separate, from an abusive partner with whom they shared children were recruited. Women were interviewed 4 times over 1 year. Results confirmed that, in addition to men's physical abuse perpetration relating to subsequent increases in mothers' depression and PTSD symptoms over time, their harm to the children predicted both mothers' depression and PTSD symptoms as well. PMID- 26872508 TI - The Prevalence and Correlates of Physical and Sexual Violence Affecting Female Sex Workers in Swaziland. AB - Female sex workers (FSW) have a heightened vulnerability to violence and negative sexual/reproductive health outcomes. Limited research has examined how experiencing physical and sexual violence (PSV) mediates risk for poor health outcomes among FSW in Swaziland. The present analyses aim to contribute to literature linking violence with poor health outcomes, high-risk behaviors, and reduced health service-seeking among FSW. Data were analyzed from a cross sectional study conducted in Swaziland between July and September 2011 with 325 adult women who reported exchanging sex for money, goods, or favors in the last 12 months, recruited through respondent-driven sampling (RDS). Logistic regression was used to assess the relationship between PSV and ancillary violence/abuse exposures, risk behaviors, and sexual/reproductive and mental health outcomes. PSV was conceptualized as either ever having been beaten up as a result of selling sex or ever being forced to have sex since the age of 18, or both. Prevalence of PSV in this sample was 59.0% in crude estimation, and 48.4% (95% confidence interval [CI]:[39.2,57.6]) with RDS weighting. Separate RDS weighted estimates of being beaten up as a result of sex work and ever being forced to have sex were 32.4% (95%CI=[24.4,40.4]) and 33.1% (95%CI =[25.0,41.2%]), respectively. Experiencing PSV was associated with being blackmailed (adjusted odds ratio [aOR]= 1.93, 95%CI= [1.07,3.52]), non-injection drug use in the last 12 months (aOR= 1.84, 95%CI= [1.02,3.33]), and feeling afraid to seek health services as a result of selling sex (aOR = 1.74, 95%CI= [1.01,2.99]). Given these findings, violence prevention strategies should be prioritized in programs that address Swazi FSW health, empowerment, and safety. PMID- 26872509 TI - Parental and Peer Attachment Characteristics: Differentiating Between Youth Sexual and Non-Sexual Offenders and Associations With Sexual Offense Profiles. AB - Attachment deficits have been suggested as an etiological explanation underlying the development of sexually abusive behaviors and general delinquency among youth. Yet, few researchers have explored the discriminating functions of attachment characteristics or investigated attachments as a stand-alone risk/protective factor explaining offending profiles among youth sexual offenders. This article explored the differences in characteristics of parental and peer attachments between youth sexual ( n = 355) and non-sexual offenders ( n = 150). Furthermore, associations between family and peer attachments and criminal profiles of sexual offenders were tested. The t-test results revealed that the groups of youth differed on various mother and father attachment characteristics, with youth sexual offenders exhibiting greater deficits. Regression models revealed lower levels of mother and peer trust and communication were associated with more severe sexual offenses; low levels of mother trust were associated with more victims; and low levels of mother trust and high father alienation were associated with more non-sexual criminality. Practice implications suggest the need to amalgamate families more consistently into treatment and addressing peer dynamics within groups and community contexts. PMID- 26872511 TI - Service user led organisations in mental health today. AB - BACKGROUND: Since 1990, health policy in England has stressed the importance of user involvement in shaping and delivering services. AIMS: To explore mental health service user-led organisations (ULOs) in England, as they interact with decision-makers to bring about change desired by them with a focus on institutional norms behaviour and specialised knowledge impacting service users' relationships with services. METHOD: An ethnography of five ULOs in two provider organisations (NHS Trusts) including observing their meetings and interactions with decision-makers, conducting in-depth interviews and collecting reflective diaries kept by two members of each group. RESULTS: During the study, one group ceased to operate. This was a group which refused to adopt the institutional rules and norms of managerial discourse. The other four groups survived by navigating the changing environment which existed at the time of the study, although often at some cost. Themes of autonomy and leadership were also identified. CONCLUSION: The current environment is one of the organisational complexity and change and the place of ULOs is an ambiguous one as they strive to maintain autonomy whilst at the same time being an acceptable voice to managers. PMID- 26872510 TI - Potential of APDM mobility lab for the monitoring of the progression of Parkinson's disease. AB - APDM's Mobility Lab system provides portable, validated, reliable, objective measures of balance and gait that are sensitive to Parkinson's disease (PD). In this review, we describe the potential of objective measures collected with the Mobility Lab system for tracking longitudinal progression of PD. Balance and gait are among the most important motor impairments influencing quality of life for people with PD. Mobility Lab uses body-worn, Opal sensors on the legs, trunk and arms during prescribed tasks, such as the instrumented Get Up and Go test or quiet stance, to quickly quantify the quality of balance and gait in the clinical environment. The same Opal sensors can be sent home with patients to continuously monitor the quality of their daily activities. Objective measures have the potential to monitor progression of mobility impairments in PD throughout its course to improve patient care and accelerate clinical trials. PMID- 26872512 TI - Early-stage hip involvement in patients with ankylosing spondylitis: A Chinese study based on magnetic resonance imaging. AB - OBJECTIVES: To evaluate the clinical characteristics and identify potential factors of the early-stage hip involvement in patients with ankylosing spondylitis (AS) based on the magnetic resonance imaging (MRI). METHODS: A cross sectional retrospective study of 655 consecutive patients was performed. Patients with hip pain or limited hip function but lacking definitive evidence of hip involvement on radiography underwent hip MRI. Based on the results of the imaging tests, the patients were classified into three categories: (1) no hip involvement; (2) early-stage hip involvement according to MRI but not radiography; (3) advanced-stage hip involvement according to a Bath Ankylosing Spondylitis Radiology Index-hip score >=2. RESULTS: One hundred and sixty-eight patients had early-stage hip involvement and 103 patients had advanced-stage hip involvement. Multivariate logistic regression analysis indicated that younger age at onset, worse BASMI score, and more active inflammation in the sacroiliac joints were associated with the occurrence of early-stage hip involvement. CONCLUSION: Negative plain radiography results cannot be used to rule out hip involvement. MRI was superior to radiography for the detection of early-stage hip involvement. Susceptible AS patients with symptoms or risk factors for hip involvement should undergo hip MRI to test for lesions in the early stage. PMID- 26872513 TI - Editorial Comment. PMID- 26872514 TI - The Relationship Between Nursing Experience and Education and the Occurrence of Reported Pediatric Medication Administration Errors. AB - Medication errors are one of the most common incidents in the hospitals. They can be harmful, and they are even more detrimental for pediatric patients. This study explored the relationship between nursing experience, education, the frequency and severity of reported pediatric medication administration errors (PMAEs). The data for this study were collected from a larger pan Canadian study. A survey tool was developed to collect self-reported data from nurses. In addition to descriptive statistics, a Poisson regression or a multiple linear regression was completed to address the research questions, and a Boneferrai correction was conducted to adjust for the small sample size. Results demonstrated that on units with more nurses with a higher level of current experience, more PMAEs were reported (p=.001), however; the PMAEs reported by these nurses were not as severe (p=.003). Implications to advance both safe medication delivery in the pediatric setting and safe culture of reporting for both actual and potential errors are identified. PMID- 26872515 TI - Relationship Between Clinical Outcomes and Spontaneous Canal Remodeling in Thoracolumbar Burst Fracture. AB - OBJECTIVES: To analyze the relationship between clinical factors and spontaneous canal remodeling. METHODS: We evaluated computed tomography scans, before surgery, within a week after surgery, 6 months after surgery, and 12 months after surgery. Thirty-eight consecutive patients who underwent posterior fixation and fusion after thoracolumbar burst fractures were included in. Factors potentially affecting the postoperative degree of reduction and spontaneous spinal remodeling were defined as age, location, degree of change of anterior vertebral compression ratio, fracture type of the retropulse bone, presence of injury to the posterior longitudinal ligament, and posterolateral complex fracture. Multiple regression analyses were conducted on these factors to analyze the extent of their influence on the reduction and resorption rates. RESULTS: The recovery rate of the anterior compression (P = 0.003) was significantly related to the reduction rate after surgery; in addition, the recovery rate of the anterior compression (P = 0.022) and the comminuted type of fracture (P = 0.019) were significantly associated with the resorption rate after surgery. CONCLUSIONS: During posterior fixation, the degree of the reduction of the vertebral body by distraction can affect the degree of postoperative reduction and spontaneous bone remodeling. Therefore, close attention must be given to the indirect reduction technique through distraction during the operation. Because comminuted fracture fragments affect spontaneous canal remodeling, the degree of postoperative resorption can be estimated by preoperative computed tomography imaging. PMID- 26872516 TI - Why Doctors Scan Patients Until They Glow. PMID- 26872517 TI - Traumatic Brain Injury Guidelines and Outcome: Please Don't Forget Postacute Care! PMID- 26872518 TI - Hyponatremia After Pituitary Surgery. PMID- 26872519 TI - Phantom Radiculopathy: Case Report and Review of the Literature. AB - BACKGROUND: Phantom radicular pain is very uncommon. To the best of our knowledge, only 14 cases have been described in the literature. A review of the literature revealed the most common cause of phantom radicular pain to be lumbar disc herniation and, furthermore, that treatment with epidural steroid injection or surgical decompression relieves pain in almost all cases. A significant number of patients with superimposed phantom radiculopathy may be missed because of the high incidence of degenerative lumbar spine diseases in the adult population, as well as the fact that amputee patients very often present with mixed stump and phantom pain. CASE DESCRIPTION: We report a case of a patient presenting with new onset phantom radicular pain (S1 left) 4 years after an above-the-knee amputation (left). Computed tomography myelography showed compression of the left S1 nerve root caused by recurrent disc herniation and scar tissue formation after previous discectomy at L5-S1. The patient experienced temporarily relief of the sciatic pain after a fluoroscopically-guided epidural transforaminal steroid injection. Subsequent microsurgical decompression led to complete remission of the phantom radicular pain. CONCLUSIONS: Amputees experiencing recurrent phantom radicular pain or new-onset superimposed pain deserve further radiologic evaluation. PMID- 26872520 TI - Indirect Revascularization for Non-Moyamoya Disease Anterior Circulation Arterial Steno-occlusion: Clinical Features, Surgical Treatment, and Medium-Term Outcomes in Adults. AB - BACKGROUND: Symptomatic anterior arterial steno-occlusion is often associated with neurofunctional deficits or a high risk of recurrent stroke or both. Although both medical and endovascular treatments are useful and suitable, few studies have investigated the continued use of indirect encephaloduroarteriosynangiosis (EDAS) bypass in patients with non-moyamoya disease ischemia. We retrospectively investigated clinical features, surgical treatments, and medium-term outcomes of indirect revascularization for patients with non-moyamoya disease anterior circulation arterial steno-occlusion in China. METHODS: EDAS without burr holes was performed in 51 adult patients with cerebral ischemic events and diagnosed nonmoyamoya anterior circulation arterial steno occlusion. Preoperative, postoperative, and follow-up neurologic status was evaluated using the National Institutes of Health Stroke Scale; changes on angiography and perfusion-weighted magnetic resonance imaging were evaluated. RESULTS: Unilateral EDAS was performed in 48 patients, and bilateral EDAS was performed in 3 patients. Four patients experienced complications before hospital discharge; only 23 patients underwent follow-up angiograms. Of the 51 patients, 44 (86.3%) exhibited improved muscle strength; 21 of 23 patients (91.3%) with follow-up angiography data exhibited evidence of new visible branches from the superficial temporal artery or middle meningeal artery or both. Preoperative and postoperative perfusion-weighted magnetic resonance imaging was performed for 5 patients. Despite clinical improvement in all patients, only 2 exhibited hemodynamic improvement. CONCLUSIONS: Indirect revascularization may be safe and effective for improving blood flow to the ischemic region following nonmoyamoya anterior circulation arterial steno-occlusion, especially in patients with residual postinfarction neurologic deficits. Our study demonstrates that improvements in ischemic symptoms after EDAS correspond to neovascularization from the superficial temporal artery or middle meningeal artery in ischemic brain areas. PMID- 26872521 TI - Comparison of the Mechanical Characteristics of a Universal Small Biplane Plating Technique Without Compression Screw and Single Anatomic Plate With Compression Screw. AB - To better understand the mechanical characteristics of biplane locked plating in small bone fixation, the present study compared the stability under cyclic cantilever loading of a 2-plate locked biplane (BPP) construct without interfragmentary compression with that of a single-plate locked construct with an additional interfragmentary screw (SPS) using surrogate bone models simulating Lapidus arthrodesis. In static ultimate plantar bending, the BPP construct failed at significantly greater load than did the SPS construct (556.2 +/- 37.1 N versus 241.6 +/- 6.3 N, p = .007). For cyclic failure testing in plantar bending at a 180-N starting load, the BPP construct failed at a significantly greater number of cycles (158,322 +/- 50,609 versus 13,718 +/- 10,471 cycles) and failure load (242.5 +/- 25.0 N versus 180.0 +/- 0.0 N) than the SPS construct (p = .002). For cyclic failure testing in plantar bending at a 120-N starting load, the results were not significantly different between the BPP and SPS constructs for the number of cycles (207,646 +/- 45,253 versus 159,334 +/- 69,430) or failure load (205.0 +/- 22.4 N versus 185.0 +/- 33.5 N; p = .300). For cyclic testing with 90 degrees offset loading (i.e., medial to lateral bending) at a 120-N starting load, all 5 BPP constructs (tension side) and 2 of the 5 SPS constructs reached 250,000 cycles without failure. Overall, the present study found the BPP construct to have superior or equivalent stability in multiplanar orientations of force application in both static and fatigue testing. Thus, the concept of biplane locked plating, using 2 low profile plates and unicortical screw insertion, shows promise in small bone fixation, because it provides consistent stability in multiplanar orientations, making it universally adaptable to many clinical situations. PMID- 26872522 TI - Surgical Outcomes for Resection of the Dorsal Exostosis of the Metatarsocuneiform Joints. AB - A retrospective case series testing the efficacy of surgical resection of the dorsal exostosis deformity of the metatarsocuneiform joints was performed. Surgery was performed in 26 consecutive patients (28 feet), in whom previous conservative therapy had failed. All 26 patients had bursitis at the level of the dorsal exostosis deformity. The patients were separated into 2 groups: group 1, those with bursitis and neuritis before surgery (n = 13; 46.4%), and group 2, those with bursitis without neuritis (n = 15; 53.5%). Both groups were evaluated using an 11-point visual analog scale administered preoperatively and <=1 year postoperatively. The mean pain rating in the patients with neuritis and bursitis before surgery (7.31 +/- 2.8) and in those with bursitis without neuritis (6.67 +/- 3.4) had both decreased to 0 at 6 months and 1 year after surgery. After surgery, 7 patients (25.2%) experienced neuritis. Of these 7 patients, 4 (57.1%) had continuation of neuritis that was present before surgery and 3 (42.9%) had an onset of neuropraxia that was secondary to the surgery itself. This might have resulted from retraction of the nerves during spur removal. Eventually, all the cases of neuritis resolved. One patient (3.6%) experienced regrowth of their dorsal exostosis deformity, 1 (3.6%) developed an abscess at the surgical site, and 1 (3.6%) developed pain elsewhere at the Lisfranc joint. All patients were subsequently treated at our institution and were pain free and had returned to full activity within 1 year. These results suggest that resection of the dorsal exostosis deformity of the metatarsocuneiform joints is an effective surgical procedure for patients with this deformity. PMID- 26872523 TI - The Neglected Achilles Tendon Rupture Repaired With Allograft: A Review of 14 Cases. AB - Various surgical techniques have been reported for the repair of neglected Achilles tendon ruptures, including V-Y advancements, synthetic augmentations, and collagen implants. The use of an Achilles tendon allograft allows bridging of large defects without donor site morbidity, with a relative ease of technique and adequate graft availability. The present retrospective report focused on the outcomes of a series of 14 patients with neglected ruptures treated with an Achilles tendon allograft. Patients were included in the present series if they had >=12 months of postoperative follow-up data available and the allograft had been used without any adjunctive procedures. Of the 14 patients, 6 were female (43%) and 8 were male (57%), with a mean follow-up period of 16.1 +/- 3 (range 12 to 27) months. The mean interval from the initial injury to surgery was 6.9 +/- 5 (range 1 to 28) months. The mean intraoperative defect size was 7.0 +/- 3 (range 4 to 15) cm. A calcaneal block was used in 2 patients (14%). All patients were able to perform a single heel rise at a mean of 27 +/- 11 (range 12 to 37) weeks postoperatively. Weightbearing in normal shoe gear was achieved at a mean of 13.5 +/- 3 (range 12 to 17) weeks. Complications included 1 delayed union (7%) of the calcaneal bone block. Repair of the neglected Achilles tendon rupture with an allograft appears to be an acceptable approach, with good overall outcomes and low risk. These results suggest that this method of repair compares favorably with established alternatives. PMID- 26872524 TI - Percutaneous Deltoid Ligament Augmentation Using Suture Tape for Medial Ankle Instability. AB - Compared with lateral ankle instability, medial ankle instability has many fewer treatment strategies and fewer reconstructive options available. The best method for deltoid ligament reconstruction remains unclear. Percutaneous deltoid ligament augmentation using suture tape represents a novel alternative technique for chronic medial ankle instability. PMID- 26872525 TI - Diagnostic Characteristics of Standard Radiographs and Magnetic Resonance Imaging of Ruptures of the Tibialis Posterior Tendon. AB - The present study aimed to diagnose complete rupture (CR) and longitudinal rupture (LR) of the posterior tibial tendon (PTT) from the magnetic resonance imaging findings in patients with PTT dysfunction and to analyze and compare the radiographs from each group to identify radiographic indicators related to the progression of PTT injury that would allow the radiographic diagnosis of CR. We evaluated 32 feet in 27 patients with PTT dysfunction (mean age 66.5, range 49 to 82, years). Radiographs were used to acquire weightbearing anteroposterior images of the foot, which were used to measure the talonavicular coverage angle. Lateral images of the foot were also acquired with the patients in the standing position. These were used to measure the lateral talometatarsal angle, calcaneal pitch angle, and medial cuneiform-fifth metatarsal height. From the axial MRI findings, the patients were divided into a CR group and an LR group, and the radiographic attributes of the CR group were analyzed. Of the 32 feet in 27 patients, 12 feet (37.5%) in 11 patients displayed CR and 20 feet (62.5%) in 18 patients displayed LR. The talonavicular coverage angle was 48.3 degrees +/- 17.3 degrees in the CR group and 33.6 degrees +/- 13.6 degrees in the LR group (p = .012), and the talometatarsal angle was -28.8 degrees +/- 22.5 degrees in the CR group and 25.4 degrees +/- 14.4 degrees in the LR group (p = .596). The calcaneal pitch angle was 10.4 degrees +/- 6.7 degrees in the CR group and 10.2 degrees +/- 8.0 degrees in the LR group (p = .935). Finally, the medial cuneiform-fifth metatarsal height was -4.2 +/- 7.1 mm in the CR group and 2.1 +/- 4.7 mm in the LR group (p = .005). When a medial cuneiform-fifth metatarsal height of <=0 mm or talonavicular coverage angle of >=50 degrees was used as the diagnostic criterion for CR on weightbearing radiographs, the sensitivity was 71.4%, specificity 88.9%, and diagnostic accuracy 81.3%; hence, we believe these to be satisfactory diagnostic criteria for CR. PMID- 26872526 TI - Associations between comorbid health conditions and the use of mental health services among adults with bipolar disorder. AB - Using a nationally representative sample, this study examined to what extent the number of comorbid health conditions was associated with various mental health service utilization among people with bipolar disorder. The results of logistic regression models indicate that a greater number of comorbid medical conditions were associated with higher odds of using specialty mental health service, while they were not associated with utilization of services provided by general health care providers. The type of bipolar disorder, functional impairment, and marital status were found to be associated with the use of a specialty service, while ethnicity was the only covariate significantly related to general health care use. PMID- 26872527 TI - Erratum. PMID- 26872529 TI - Loop-mediated isothermal amplification assay for rapid and sensitive detection of sheep pox and goat pox viruses in clinical samples. AB - A Loop-mediated isothermal amplification (LAMP) assay targeting the highly conserved DNA polymerase gene of capripox virus genome was developed and evaluated for rapid detection of sheep pox and goat pox viruses. The optimized LAMP assay is found specific and sensitive for amplification of target DNA with a diagnostic sensitivity and specificity of 96.6% and 100% respectively compared to quantitative PCR. The detection rate of LAMP, PCR and Q-PCR assays is found to be 81.5%, 67% and 83% respectively. This LAMP assay has the potential for rapid clinical diagnosis and surveillance of sheep pox and goat pox in field diagnostic laboratories. PMID- 26872528 TI - Language and understanding of cardiopulmonary resuscitation amongst an aged inpatient population. AB - Greater patient involvement in health decision-making requires exchange of information between the patient and the healthcare professionals. Decisions regarding healthcare at the end of life include consideration of cardiopulmonary resuscitation (CPR). The stated objectives of this study were to determine how often language around concepts of resuscitation is used in the community by examination of the English language corpora (ELC); to explore the understanding of the same language by a group of older hospital patients; and to determine the patients' knowledge of the process and success of CPR, as well as the sources of their information. Medical inpatients aged 75 years and older were surveyed to this end in the setting of a tertiary university teaching hospital. Interrogation of the Australian, British and American English Corpora was accomplished by a linguist, and a questionnaire and semi-structured interview were administered to ascertain patient knowledge. We demonstrated that although medical inpatients have some familiarity with terms relating to resuscitation, there is a lack of understanding of the context, process and outcomes of CPR. The predominant sources of information were television and print media. Examination of the ELC revealed a paucity of the use of terms related to resuscitation. This finding indicates that physicians have a duty of care to determine patients' understanding around resuscitation language, and terms used, in discussions of their preferences before assuming their engagement in shared decision-making. More open public discussion around death and resuscitation would increase the general knowledge of the population and would provide a better foundation for the discussions in times of need. PMID- 26872530 TI - New polymorphisms within the variable number tandem repeat (VNTR) 7 locus of Mycobacterium avium subsp. paratuberculosis. AB - Variable number tandem repeat (VNTR) is a frequently employed typing method of Mycobacterium avium paratuberculosis (MAP) isolates. Based on whole genome sequencing in a previous study, allelic diversity at some VNTR loci seems to over or under-estimate the actual phylogenetic variance among isolates. Interestingly, two closely related isolates on one farm showed polymorphism at the VNTR 7 locus, raising concerns about the misleading role that it might play in genotyping. We aimed to investigate the underlying basis of VNTR 7 polymorphism by analyzing sequence data for published genomes and field isolates of MAP and other M. avium complex (MAC) members. In contrast to MAP strains from cattle, strains from sheep displayed an "imperfect" repeat within VNTR 7, which was identical to respective allele types in other MAC genomes. Subspecies- and strain-specific single nucleotide polymorphisms (SNPs) and two novel (16 and 56 bp) repeats were detected. Given the combination of the three existing repeats, there are at least five different patterns for VNTR 7. The present findings highlight a higher polymorphism and probable instability of VNTR 7 locus that needs to be considered and challenged in future studies. Until then, sequencing of this locus in future studies is important to correctly assign the underlying allele types.(1). PMID- 26872531 TI - Phylogeography and evolution of the Red Salamander (Pseudotriton ruber). AB - Phylogeographic studies frequently result in the elevation of subspecific taxa to species given monophyly, or the synonymy of subspecies that are not monophyletic. However, given limited or incongruent datasets, retention of subspecies can be useful to describe hypothesized incipient species or to illustrate interesting biological phenomena driving morphological diversity. Four subspecific taxa have been used to describe largely allopatric geographic variation within the species Pseudotriton ruber, a plethodontid salamander occupying stream and spring habitats across eastern North America: P. r. vioscai occurs in lowland Coastal Plain habitats, while P. r. ruber, P. r. nitidus, and P. r. schencki occupy upland regions in and around the Appalachian Mountains. Pseudotriton ruber co occurs through its distribution with the aposematic newt Notophthalmus viridescens, and both species are hypothesized to be part of a Mullerian mimicry complex. In this study, we sequenced regions of two mitochondrial (cytochrome b, NADH dehydrogenase subunit 2) and one single copy nuclear protein-coding gene (pro-opiomelanocortin) from individuals sampled across much of the distribution of P. ruber and then used maximum-likelihood and Bayesian phylogenetic inference to test the monophyly of subspecies, reconstruct biogeographic history, and make inferences about morphological evolution. Phylogeographic hypotheses from mitochondrial and nuclear datasets described structure among populations of P. ruber which separated Coastal Plain and upland Appalachian populations, but subspecies were not monophyletic. Biogeographic reconstruction estimated the ancestor of all populations to have occupied and initially diverged in the Coastal Plain during the Pliocene (~3.6mya), before one lineage subsequently invaded upland areas of Appalachia. Bold bright coloration of high elevation subspecies P. r. nitidus and P. r. schencki appears to have evolved twice. We hypothesize that the Mullerian mimicry complex with N. viridescens and P. ruber may provide a selective mechanism driving the co-evolution of striking bright and dull morphological variation among populations of both species. While P. ruber subspecies were not consistent with our criteria for diagnosing species (monophyly) and therefore could not be elevated to species, we advocate for the retention of subspecies because they describe hypotheses about an incipient species (P. r. vioscai) and how Mullerian mimicry may shape morphological diversity of species. PMID- 26872533 TI - Cuticle expansion during feeding in the tick Amblyomma hebraeum (Acari: Ixodidae): The role of hydrostatic pressure. AB - Female Amblyomma hebraeum ticks (Acari: Ixodidae) increase their weight ~10-fold during a 'slow phase of engorgement' (7-9 days), and a further 10-fold during the 'rapid phase' (12-24h). During the rapid phase, the cuticle thins by half, with a plastic (permanent) deformation of greater than 40% in two orthogonal directions. A stress of 2.5 MPa or higher is required to achieve this degree of deformation (Flynn and Kaufman, 2015). Using a dimensional analysis of the tick body and applying the Laplace equation, we calculated that the tick must achieve high internal hydrostatic pressures in order to engorge fully: greater than 55 kPa at a fed:unfed mass ratio of ~20:1, when cuticle thinning commences (Flynn and Kaufman, 2011). In this study we used a telemetric pressure transducer system to measure the internal hydrostatic pressure of ticks during feeding. Sustained periods of irregular high frequency (>20 Hz) pulsatile bursts of high pressure (>55 kPa) were observed in two ticks: they had been cannulated just prior to the rapid phase of engorgement, and given access to a host rabbit for completion of the feeding cycle. The pattern of periods of high pressure generation varied over the feeding cycle and between the two specimens. We believe that these pressures exceed those reported so far for any other animal. PMID- 26872532 TI - Copper and protons directly activate the zinc-activated channel. AB - The zinc-activated channel (ZAC) is a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC is the least understood member of this family so in the present study we sought to characterize the properties of this channel further. We demonstrate that not only zinc (Zn(2+)) but also copper (Cu(2+)) and protons (H(+)) are agonists of ZAC, displaying potencies and efficacies in the rank orders of H(+)>Cu(2+)>Zn(2+) and H(+)>Zn(2+)>Cu(2+), respectively. The responses elicited by Zn(2+), Cu(2+) and H(+) through ZAC are all characterized by low degrees of desensitization. In contrast, currents evoked by high concentrations of the three agonists comprise distinctly different activation and decay components, with transitions to and from an open state being significantly faster for H(+) than for the two metal ions. The permeabilities of ZAC for Na(+) and K(+) relative to Cs(+) are indistinguishable, whereas replacing all of extracellular Na(+) and K(+) with the divalent cations Ca(2+) or Mg(2+) results in complete elimination of Zn(2+)-activated currents at both negative and positive holding potentials. This indicates that ZAC is non-selectively permeable to monovalent cations, whereas Ca(2+) and Mg(2+) inhibit the channel. In conclusion, this is the first report of a Cys-loop receptor being gated by Zn(2+), Cu(2+) and H(+). ZAC could be an important mediator of some of the wide range of physiological functions regulated by or involving Zn(2+), Cu(2+) and H(+). PMID- 26872534 TI - Sirt1 is essential for resveratrol enhancement of hypoxia-induced autophagy in the type 2 diabetic nephropathy rat. AB - Type 2 diabetic nephropathy (DN) is a serious end-stage kidney disease worldwide. Multiple studies demonstrate that resveratrol (RSV) has a beneficial effect on DN. However, whether RSV-induced improvement in kidney function in diabetes is due to the regulation of autophagy remains unclear. Here, we investigated the mechanisms underlying RSV-mediated protection against DN in diabetic rats, with a special focus on the role of NAD-dependent deacetylase sirtuin 1 (Sirt1) in regulating autophagy. We found that long-term RSV treatment in rats promoted Sirt1 expression and improved related metabolic levels in the diabetic kidney. Our study showed that, in cultured NRK-52E cells, Sirt1 knockdown inhibited the autophagy levels of proteins Atg7, Atg5, and LC3 and impaired the RSV amelioration of dysfunctional autophagy under hypoxic condition. Furthermore, exposed to 1% O2 over time induced autophagy dysfunction and apoptosis in NRK-52E cells, which could be improved by RSV treatment. Our data highlight the role of the Sirt1-mediated pathway in the effects of RSV on autophagy in vivo and in vitro, suggesting RSV could be a potential new therapy for type 2 DN. PMID- 26872535 TI - Comparative prognostic relevance of breast intra-tumoral microvessel density evaluated by CD105 and CD146: A pilot study of 42 cases. AB - Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. AIM: The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. METHODS: 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. RESULTS: High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). CONCLUSION: Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer. PMID- 26872536 TI - The relation between percentage of immunostained cells and amplification status in breast cancers with equivocal result for Her2 immunohistochemistry. AB - We analyzed Her2 amplification in breast cancers with equivocal IHC staining to investigate the significance of percentage of Her2 immunostained tumor cells. We especially included the breast cancers with complete/incomplete membrane staining at moderate intensity in less than 10% of the invasive tumor cells. Of 1804 breast cases, 180 had moderate complete/incomplete membrane Her2 immunostaining. According to 2013 ASCO/CAP guideline, 124 were in IHC score 2+ and 56 in 1+ category. The percentage of Her2 immunostained invasive tumor cells were determined by visual estimation at the time of diagnosis and categorized into three groups; <10%, 10-50%, and >50% for this review. FISH was performed by dual DNA probe and data of Her2/cep17 ratio, Her2/cell and Cep17/cell were recorded applying 2013 ASCO/CAP criteria. There were 22 cases (12.2%) in >50% group, 102 (56.7%) in 10-50% group, and 56 (31.1%) in <10% group. Overall Her2 amplification was 25.5%. Her2 was amplified in 12 (54.5%) cases in >50% group; 26 (25.4%) in 10 50% and 8 (14.3%) in <10%. Her2 amplification was more frequent in cancers with >50% moderately immunostained cells in IHC equivocal group. However, most of Her2 IHC equivocal breast cancers contain moderate amount (10-50%) of immunostained cells. Relatively small but non-neglectable number (14%) of cases in <10% group was Her2 amplified by FISH which approaches to overall incidence of Her2 overexpression (15-20%) in all breast cancer. Breast cancers with moderate complete/incomplete membrane Her2 IHC staining in <10% of invasive tumor cells should be regarded as equivocal and reflex FISH should be performed in these cases. PMID- 26872537 TI - Structural damage to the hip in systemic juvenile idiopathic arthritis: A case of regression with Anakinra. PMID- 26872538 TI - Impact of endo- and exogenous estrogens on heart rate variability in women: a review. AB - Measurement of heart rate variability (HRV) is an established method to assess the activity of the autonomic nervous system. The aim of this review was to examine the link between HRV, reproductive life stages and menopausal hormone therapy. A literature review was performed using the Medline database. Based on title and abstract, 45 studies were extracted out of 261 citations screened. Due to different study designs and evaluation methods, HRV indices were not directly comparable. Qualitative comparisons in between the vast majority of studies, however, demonstrated a decrease of the vagal dominance on the heart from the follicular to the luteal cycle phase, although some studies asserted no change. The intake of oral contraceptives appeared not to alter the vagal modulation of the heart. All investigations agreed on a decline of HRV towards higher sympathetic control after menopause. Different menopausal hormone therapy approaches showed a supporting impact of estrogen on HRV in most studies. A combined therapy of estrogen and progestogens revoked this benefit. Further research is needed to demonstrate how this process might be attenuated by different menopausal hormone therapies. PMID- 26872539 TI - Reply. PMID- 26872541 TI - Changes to nitrate isotopic composition of wastewater treatment effluent and rivers after upgrades to tertiary treatment in the Narragansett Bay watershed, RI. AB - Due to nitrogen load reduction policies, wastewater treatment facilities (WWTFs) have upgraded to tertiary treatment - where denitrification reduces and removes nitrogen. Changes to the stable isotopic composition of nitrate inputs after upgrades or how it transfers to the estuary have not been assessed in Rhode Island. We investigate whether these upgrades impact the isotopic signature of nitrate inputs to Narragansett Bay. Samples from rivers and WWTFs discharging to Narragansett Bay characterize the anthropogenic source nitrate (NO3(-)) isotopic composition (delta(15)N-NO3(-) and delta(18)O-NO3(-)) and temporal variability. At one WWTF, tertiary treatment increased effluent nitrate delta(15)N-NO3(-) and delta(18)O-NO3(-) values by ~160/00. Riverine values increased by ~40/00, likely due to the combination of decreases in N and upgrades. Combined river and WWTF flux-weighted isotopic compositions showed enriched values and an amplitude reduction in monthly variability. When seasonal isotopic means are significantly different from other sources, delta(15)N-NO3(-) may be a useful tracer of inputs. PMID- 26872540 TI - Insulin-like growth factor 2 modulates murine hematopoietic stem cell maintenance through upregulation of p57. AB - Hematopoietic stem cells (HSC) rely on a highly regulated molecular network to balance self-renewal and lineage specification to sustain life-long hematopoiesis. Despite a plethora of studies aimed at identifying molecules governing HSC fate, our current knowledge of the genes responsible is limited. We have found insulin-like growth factor 2 (IGF2) to be expressed predominantly within long-term HSCs. This study examines IGF2 expression patterns and the effects of the gene in HSCs. Through the overexpression and knockdown of IGF2 within purified HSCs, we report that IGF2 expression increases HSC-derived multilineage colonies in vitro and enhances hematopoietic contribution in vivo on competitive bone marrow transplantation. The effects of IGF2 are mediated by direct upregulation of the CDKi p57, exclusively within long-term HSCs, via activation of the PI3K-Akt pathway. Increased expression of p57 resulted in a concomitant increase in HSCs in the G0/G1 stage of the cell cycle. Analysis of genomic DNA methylation revealed that HSCs exhibited a hypomethylated state within the promoter region of the CDKN1C (p57) gene, providing a potential mechanism for the exclusive effects of IGF2 within HSCs. Our studies indicate a novel role for IGF2 in regulating HSC cell cycle and illustrate potential novel therapeutic targets for hematologic diseases. PMID- 26872542 TI - Trace metal contamination in surface sediments of intertidal zone from Qinhuangdao, China, revealed by geochemical and magnetic approaches: Distribution, sources, and health risk assessment. AB - Based on geochemical and magnetic approaches, the distribution, sources, and health risk of trace metals in surface sediments from a seashore tourist city were investigated. A significant correlation was found between magnetic susceptibility (chi) and trace metals, which suggested that levels of trace metals in the sediments can be effectively depicted by the magnetic approach. The spatial distribution of chi and trace metals matched well with the city layout with relatively higher values being found in the port and busy tourist areas. This result, together with enrichment factors (EFs) and Tomlinson pollution load index (PLI) of metals, suggested that the influence of human activities on the coastal environment was noticeable. Principal component analysis (PCA) indicated that trace metals in the sediments were derived from both anthropogenic and natural sources. Noncarcinogenic risk assessment showed that there was no potential health risk of exposure to metals by means of ingestion or inhalation. PMID- 26872543 TI - Purification and characterization of a fish granzymeA involved in cell-mediated immunity. AB - Granzymes are serine proteases involved in the induction of cell death against non-self cells. The enzymes differ in their primary substrate specificity and have one of four hydrolysis activities: tryptase, Asp-ase, Met-ase and chymase. Although granzyme genes have been isolated from several fishes, evidence for their involvement in cytotoxicity has not yet been reported. In the present study, we attempted to purify and characterize a fish granzyme involved in cytotoxicity using ginbuna crucian carp. The cytotoxicity of leukocytes was significantly inhibited by the serine protease inhibitor ''3, 4 dichloroisocoumarin''. In addition, we found that granzymeA-like activity (hydrolysis of Z-GPR-MCA) was inhibited by the same inhibitor and significantly enhanced by allo-antigen stimulation in vivo. Proteins from leukocyte extracts were subjected to two steps of chromatographic purification using benzamidine Sepharose and SP-Sepharose. The molecular weight of the purified enzyme was estimated to be 26,900 Da by SDS-PAGE analysis. The purified enzyme displayed a Km of 220 MUM, a Kcat of 21.7 sec(-1) and a Kcat/Km of 98,796 sec(-1) M(-1) with an optimal pH of 9.5 for the Z-GPR-MCA substrate. The protease was totally inhibited by serine protease inhibitors and showed granzymeA-like substrate specificity. Therefore, we conclude that the purified enzyme belongs to the mammalian granzymeA (EC 3.4.21.78) and appears to be involved in cytotoxicity in fish. PMID- 26872544 TI - Gut immunity in Lepidopteran insects. AB - Lepidopteran insects constitute one of the largest fractions of animals on earth, but are considered pests in their relationship with man. Key to the success of this order of insects is its ability to digest food and absorb nutrition, which takes place in the midgut. Because environmental microorganisms can easily enter Lepidopteran guts during feeding, the innate immune response guards against pathogenic bacteria, virus and microsporidia that can be devoured with food. Gut immune responses are complicated by both resident gut microbiota and the surrounding peritrophic membrane and are distinct from immune responses in the body cavity, which depend on the function of the fat body and hemocytes. Due to their relevance to agricultural production, studies of Lepidopteran insect midgut and immunity are receiving more attention, and here we summarize gut structures and functions, and discuss how these confer immunity against different microorganisms. It is expected that increased knowledge of Lepidopteran gut immunity may be utilized for pest biological control in the future. PMID- 26872546 TI - Antigen sampling in the fish intestine. AB - Antigen uptake in the gastrointestinal tract may induce tolerance, lead to an immune response and also to infection. In mammals, most pathogens gain access to the host though the gastrointestinal tract, and in fish as well, this route seems to be of significant importance. The epithelial surface faces a considerable challenge, functioning both as a barrier towards the external milieu but simultaneously being the site of absorption of nutrients and fluids. The mechanisms allowing antigen uptake over the epithelial barrier play a central role for maintaining the intestinal homeostasis and regulate appropriate immune responses. Such uptake has been widely studied in mammals, but also in fish, a number of experiments have been reported, seeking to reveal cells and mechanisms involved in antigen sampling. In this paper, we review these studies in addition to addressing our current knowledge of the intestinal barrier in fish and its anatomical construction. PMID- 26872545 TI - Role of histamine in the regulation of intestinal immunity in fish. AB - In mammals, during the acute inflammatory response, the complex interrelationship and cross-talk among histamine and the immune system has been fairly well characterized. There is a substantial body of information on its structure, metabolism, receptors, signal transduction, physiologic and pathologic effects. However, for early vertebrates, there is little such knowledge. In the case of teleost fish, this lack of knowledge has been due to the widely held belief that histamine is not present in this phylogenetic group. However, it has been recently demonstrated, that granules of mast cells in perciforms contain biologically active histamine. More importantly, the inflammatory response was clearly demonstrated to be regulated by the direct action of histamine on professional phagocytes. Nevertheless, the molecular basis and exact role of this biogenic amine in perciforms is still a matter of speculation. Therefore, this review intends to summarize recent experimental evidence regarding fish mast cells and correlate the same with their mammalian counterparts to establish the possible role of histamine in the fish intestinal inflammatory response. PMID- 26872547 TI - The effect of rapamycin on biodiesel-producing protist Euglena gracilis. AB - Rapamycin induces autophagy with lipid remodeling in yeast and mammalian cells. To investigate the lipid biosynthesis of Euglena gracilis, rapamycin was supplemented in comparison with two model algae, Chlamydomonas reinhardtii and Cyanidioschyzon merolae. In Euglena, rapamycin induced the reduction of chlorophylls and the accumulation of neutral lipids without deterring its cell proliferation. Its lipidomic profile revealed that the fatty acid composition did not alter by supplementing rapamycin. In Chlamydomonas, however, rapamycin induced serious growth inhibition as reported elsewhere. With a lower concentration of rapamycin, the alga accumulated neutral lipids without reducing chlorophylls. In Cyanidioschyzon, rapamycin did not increase neutral lipids but reduced its chlorophyll content. We also tested fatty acid elongase inhibitors such as pyroxasulfone or flufenacet in Euglena with no significant change in its neutral lipid contents. In summary, controlled supplementation of rapamycin can increase the yield of neutral lipids while the scheme is not always applicable for other algal species. PMID- 26872549 TI - Fractures lead to worsening of disease activity in rheumatoid arthritis. AB - OBJECTIVES: The cause of rheumatoid arthritis (RA) flares is multifactorial and not well understood. No reports of fractures influencing disease activity in patients with RA have been published. The purpose of this study was to determine whether fractures influence disease activity in patients with RA. METHODS: Hospital records of 470 patients with RA between 2011 and 2014 were analyzed. We first examined the incidence of flare using multiple regression analysis. Secondly, we examined the incidence of flare using DAS28-ESR, DAS28-CRP, and drug changes before bone fracture until bone union in the fracture cases. RESULTS: Multiple linear regression analysis showed that female sex (p < 0.001), bottom DAS28-ESR (p < 0.001), and fracture (p = 0.041) were independent factor for DAS28 ESR at the last observation period, and sex (p = 0.040), bottom DAS28-CRP (p < 0.001), and fracture (p = 0.019) were independent factor for DAS28-CRP at the last observation period. The average DAS28-ESR value was significantly increased from 3.19 (prefracture) to 3.58 (bone union). The average DAS28-CRP value was also significantly increased from 2.45 (prefracture) to 2.79 (bone union). CONCLUSIONS: We have demonstrated that fractures influence disease activity in patients with RA. Larger numbers of fracture cases are required to confirm the present observations; however, the prevention of fracture is clearly required in patients with RA. PMID- 26872548 TI - Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial. AB - BACKGROUND: Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. OBJECTIVE: To investigate the effects of intraileal infusion of native casein on plasma amino acid appearance, immune activation and gastrointestinal (GI) symptoms. DESIGN: A randomized single-blind cross over study was performed in 13 healthy subjects (6 male; mean age 26 +/- 2.9 years; mean body mass index 22.8 +/- 0.4 kg/m-2), who were intubated with a naso-ileal feeding catheter. Thirty minutes after intake of a standardized breakfast, participants received an ileal infusion, containing either control (C) consisting of saline, a low-dose (17.2 kcal) casein (LP) or a high-dose (51.7 kcal) of casein (HP) over a period of 90 min. Blood samples were collected for analysis of amino acids (AAs), C-reactive protein (CRP), pro inflammatory cytokines and oxylipins at regular intervals. Furthermore, GI symptom questionnaires were collected before, during and after ileal infusion. RESULTS: None of the subjects reported any GI symptoms before, during or after ileal infusion of C, LP and HP. Plasma concentrations of all AAs analyzed were significantly increased after infusion of HP as compared to C (p < 0.001), and most AAs were increased after infusion of LP (p < 0.001). In total, 12.49 +/- 1.73 and 3.18 +/- 0.87 g AAs were found in plasma after intraileal infusion of HP and LP, corresponding to 93 +/- 13% (HP) and 72 +/- 20% (LP) of AAs infused as casein, respectively. Ileal casein infusion did not affect plasma concentrations of CRP, IL-6, IL-8, IL-1beta and TNF-alpha. Infusion of HP resulted in a decreased concentration of 11,12-dihydroxyeicosatrienoic acid whereas none of the other oxylipins analyzed were affected. CONCLUSIONS: A single intraileal infusion of native casein results in a concentration and time dependent increase of AAs in plasma, suggesting an effective digestion and absorption of AAs present in casein. Also, ileal infusion did not result in immune activation nor in GI symptoms. CLINICALTRIALS.GOV: NCT01509469. PMID- 26872550 TI - Editorial 2016 for Ocular Immunology and Inflammation. PMID- 26872551 TI - Scleritis. PMID- 26872552 TI - Edge activators and a polycationic polymer enhance the formulation of porous voriconazole nanoagglomerate for the use as a dry powder inhaler. AB - PURPOSE: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1-5 MUm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles. METHOD: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size. RESULTS: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p < 0.05) with R(2 )=( )0.95. Small-sized particles were formed (353 nm), while their zeta potential was -30.7 mV. The agglomerates were 2.7 MUm in size and their zeta potential was 20.9 mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p < 0.05) and higher fine particle dose (FPD) (p < 0.01), fine particle fraction (FPF) (p < 0.01), and total emitted dose (TED) (p < 0.01) than the pure powder. CONCLUSION: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung. PMID- 26872553 TI - Unhealthy Fat in Street and Snack Foods in Low-Socioeconomic Settings in India: A Case Study of the Food Environments of Rural Villages and an Urban Slum. AB - OBJECTIVE: To describe the food environment in rural villages and an urban slum setting in India with reference to commercially available unbranded packaged snacks and street foods sold by vendors, and to analyze the type and quantity of fat in these foods. DESIGN: Cross-sectional. SETTING: Two low-income villages in Haryana and an urban slum in Delhi. PARTICIPANTS: Street vendors (n = 44) were surveyed and the nutritional content of snacks (n = 49) sold by vendors was analyzed. MAIN OUTCOME MEASURES: Vendors' awareness and perception of fats and oils, as well as the type of snacks sold, along with the content and quality of fat present in the snacks. ANALYSIS: Descriptive statistics of vendor survey and gas chromatography to measure fatty acid content in snacks. RESULTS: A variety of snacks were sold, including those in unlabeled transparent packages and open glass jars. Mean fat content in snacks was 28.8 g per 100-g serving in rural settings and 29.6 g per 100-g serving in urban settings. Sampled oils contained high levels of saturated fats (25% to 69% total fatty acids) and trans fats (0.1% to 30% of total fatty acids). CONCLUSIONS AND IMPLICATIONS: Interventions need to target the manufacturers of oils and fats used in freshly prepared products to improve the quality of foods available in the food environment of low socioeconomic groups in India. PMID- 26872555 TI - Thermoluminescence of novel MgO-CeO2 obtained by a glycine-based solution combustion method. AB - Thermoluminescence dosimetry properties of novel MgO-CeO2 obtained by solution combustion synthesis in a glycine-nitrate process, are presented for the very first time. X-ray diffraction indicates the presence of cubic MgO and cerianite (CeO2) for the annealed powder samples. Dosimetry features such as linear behaviour of the dose response without saturation in the dose interval studied, as well as asymptotic behaviour of the thermoluminescent signal fading place MgO CeO2 phosphor as a promising material for low-dose radiation dosimetry applications. PMID- 26872554 TI - Short and long-term outcomes of percutaneous left atrial appendage suture ligation: Results from a US multicenter evaluation. AB - BACKGROUND: Published studies of epicardial ligation of left atrial appendage (LAA) have reported discordant results. OBJECTIVE: The purpose of this study was to delineate the safety and efficacy of LAA closure with the LARIAT device. METHODS: This is a multicenter registry of 712 consecutive patients undergoing LAA ligation with LARIAT at 18 US hospitals. The primary end point was successful suture deployment, no leak by intraprocedural transesophageal echocardiography (TEE), and no major complication (death, stroke, cardiac perforation, and bleeding requiring transfusion) at discharge. A leak of 2-5 mm on follow-up TEE was the secondary end point. RESULTS: LARIAT was successfully deployed in 682 patients (95.5%). A complete closure was achieved in 669 patients (98%), while 13 patients (1.8%) had a trace leak (<2 mm). There was 1 death related to the procedure. Ten patients (1.44%) had cardiac perforation necessitating open heart surgery, while another 14 (2.01%) did not need surgery. The risk of cardiac perforation decreased significantly after the introduction of a micropuncture (MP) needle for pericardial access. Delayed complications (pericarditis requiring >2 weeks of treatment with nonsteroidal anti-inflammatory drugs/colchicine and pericardial and pleural effusion after discharge) occurred in 34 (4.78%) patients, and the risk decreased significantly with the periprocedural use of colchicine. Follow-up TEE (n = 480) showed a leak of 2-5 mm in 6.5% and a thrombus in 2.5%. One patient had a leak of >5 mm. CONCLUSION: LARIAT effectively closes the LAA and has acceptable procedural risks with the evolution of the use of the micropuncture needle for pericardial access and the use of colchicine for mitigating the postinflammatory response associated with LAA ligation and pericardial access. PMID- 26872556 TI - Development of the sporadic inclusion body myositis physical functioning assessment. AB - INTRODUCTION: Sporadic inclusion body myositis (sIBM) is a progressive idiopathic inflammatory myopathy characterized by atrophy and weakness of proximal and distal muscle groups that results in a loss of independence and the need for assistive devices and supportive care. To assess treatment benefit of new therapies, a patient-reported outcome measure of physical function was developed. METHODS: The tool was rigorously developed in accordance with the United States Food and Drug Administration (FDA) patient-reported outcomes (PRO) guidance. A single-visit, observational study was conducted. Standard qualitative analytical methods were employed to analyze interview data and generate questionnaire items. RESULTS: Twenty concept elicitation and 19 cognitive debriefing interviews were conducted, and 6 expert physicians were consulted. The tool consists of 11 items scored on a 0-10 numerical rating scale. Subjects completed the questionnaire utilizing either paper or electronic administration. CONCLUSION: We have developed a PRO tool in alignment with FDA PRO guidance for use in the functional assessment of treatment benefit in sIBM. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 653-657, 2016. PMID- 26872558 TI - (89) Zr-rituximab PET/CT to detect neurolymphomatosis. PMID- 26872557 TI - Season of diagnosis is associated with overall survival in patients with diffuse large B-cell lymphoma but not with Hodgkin's lymphoma - A population-based Swedish Lymphoma Register study. AB - OBJECTIVE AND METHODS: The aim of this study was to investigate the effect of season of diagnosis on the outcome of patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). In this study, we included curatively treated DLBCL (n = 5875) and HL (n = 1693) patients, diagnosed between 2000 and 2011, based on data from the Swedish Lymphoma Register. RESULTS: Overall survival was significantly better for patients diagnosed with DLBCL during the summer months, but not for patients diagnosed with HL. The difference remained in a multivariable analysis adjusted for age, stage, performance status, number of extra nodal sites and year of diagnosis (HR 1.08; 95% CI 1.02-1.14, P = 0.0069). When analyzing the DLBCL patients according to gender in the multivariable model, the effect of season was shown to be restricted to male patients (HR = 1.09, 95% CI 1.01-1.17, P = 0.0269. CONCLUSIONS: In summary, season of diagnosis was shown to have impact on overall survival in male patients with DLBCL. Possible explanations of our results are the higher vitamin D level during the summer months, the effects of sunlight on the circadian rhythm and the immune system, or the lower risk of infectious disease during the summer. Further investigations are needed to explore these hypotheses. PMID- 26872559 TI - T2* and T1 assessment of abdominal tissue response to graded hypoxia and hypercapnia using a controlled gas mixing circuit for small animals. AB - PURPOSE: To characterize T2* and T1 relaxation time response to a wide spectrum of gas challenges in extracranial tissues of healthy rats. MATERIALS AND METHODS: A range of graded gas mixtures (hyperoxia, hypercapnia, hypoxia, and hypercapnic hypoxia) were delivered through a controlled gas-mixing circuit to mechanically ventilated and intubated rats. Quantitative magnetic resonance imaging (MRI) was performed on a 3T clinical scanner; T2* and T1 maps were computed to determine tissue response in the liver, kidney cortex, and paraspinal muscles. Heart rate and blood oxygen saturation (SaO2 ) were measured through a rodent oximeter and physiological monitor. RESULTS: T2* decreases consistent with lowered SaO2 measurements were observed for hypercapnia and hypoxia, but decreases were significant only in liver and kidney cortex (P < 0.05) for >10% CO2 and <15% O2 , with the new gas stimulus, hypercapnic hypoxia, producing the greatest T2* decrease. Hyperoxia-related T2* increases were accompanied by negligible increases in SaO2 . T1 generally increased, if at all, in the liver and decreased in the kidney. Significance was observed (P < 0.05) only in kidney for >90% O2 and >5% CO2 . CONCLUSION: T2* and T1 provide complementary roles for evaluating extracranial tissue response to a broad range of gas challenges. Based on both measured and known physiological responses, our results are consistent with T2* as a sensitive marker of blood oxygen saturation and T1 as a weak marker of blood volume changes. J. Magn. Reson. Imaging 2016;44:305-316. PMID- 26872560 TI - Exercise: the lifelong supplement for healthy ageing and slowing down the onset of frailty. AB - The beneficial effects of exercise have been well recognized for over half a century. Dr Jeremy Morris's pioneering studies in the fifties showed a striking difference in cardiovascular disease between the drivers and conductors on the double-decker buses in London. These studies sparked off a vast amount of research on the effects of exercise in health, and the general consensus is that exercise contributes to improved outcomes and treatment for several diseases including osteoporosis, diabetes, depression and atherosclerosis. Evidence of the beneficial effects of exercise is reviewed here. One way of highlighting the impact of exercise on disease is to consider it from the perspective of good practice. However, the intensity, duration, frequency (dosage) and counter indications of the exercise should be taken into consideration to individually tailor the exercise programme. An important case of the beneficial effect of exercise is that of ageing. Ageing is characterized by a loss of homeostatic mechanisms, on many occasions leading to the development of frailty, and hence frailty is one of the major geriatric syndromes and exercise is very useful to mitigate, or at least delay, it. Since exercise is so effective in reducing frailty, we would like to propose that exercise be considered as a supplement to other treatments. People all over the world have been taking nutritional supplements in the hopes of improving their health. We would like to think of exercise as a physiological supplement not only for treating diseases, but also for improving healthy ageing. PMID- 26872562 TI - Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy. AB - BACKGROUND: To examine the association of diabetes and diabetic retinopathy (DR) with retinal ganglion cell (RGC) loss. DESIGN: Observational case-control study. PARTICIPANTS: Type 2 diabetes cases and age-gender matched controls without diabetes. METHODS: Spectral-domain optical coherence tomography (OCT) parameters of RGCs were calculated after automated segmentation of macular scans. DR severity was graded on fundus photographs using the modified Airlie House Classification system. Generalized estimating equation was used to compare OCT parameters between cases and controls, adjusted for covariates. MAIN OUTCOME MEASURES: Average ganglion cell-inner plexiform layer (GC-IPL) and average retinal nerve fibre layer (RNFL) thicknesses. RESULTS: We analyzed 227 cases and 227 controls. The mean age (years) of cases was 58.3 and controls was 58.1 (P = 0.13). Among cases, 101 had none, 25 had mild and 101 had moderate or severe DR. Compared with controls, GC-IPL and RNFL were thinner in all cases [mean difference (95% confidence interval [CI]): GC-IPL -4.49 um (-2.92; -6.06), RNFL 0.93 um (-0.09; -1.85)], including cases with no DR [mean difference (95% CI), GC IPL -4.37 um (-2.72; -6.02), RNFL -1.06 um (-0.10; -2.02)]. Cases with any DR had thinner GC-IPL than controls [mean difference (95% CI): GC-IPL -4.81 um (-2.12; 7.50)]. Among cases, subjects with moderate or severe DR had thinner GC-IPL than subjects with no DR [mean difference (95% CI): GC-IPL -2.07 um (-0.08; -4.07)]. CONCLUSIONS: RGC loss is present in subjects with diabetes and no DR, and is progressive in moderate or severe DR. RGC neuronal damage in diabetes and DR can be clinically detected using OCT. PMID- 26872561 TI - Urolithin A, C, and D, but not iso-urolithin A and urolithin B, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes. AB - SCOPE: Urolithins (Uro) are ellagic acid (EA)-derived metabolites produced by gut microbes. There is a growing interest in the biological activities of Uro. Our aim was to evaluate the impacts of Uro on regulating triglyceride (TG) accumulation using cultures of primary human adipocytes and hepatoma Huh7 cells. METHODS AND RESULTS: UroA, UroB, UroC, UroD, and iso-UroA were used to determine the effect of Uro on adipogenesis and lipogenesis. Individual Uro (30 MUM) were added to human adipogenic stem cells during differentiation. UroA, UroC, and UroD, but not iso-UroA and UroB, significantly inhibited new fat cell formation by decreasing TG accumulation and adipogenic protein and gene expressions. The regulation of TG synthesis by Uro was investigated via metabolic chasing with radiolabeled precursors. UroA, UroC, and UroD attenuated TG accumulation, while increasing the fatty acid (FA) oxidation in adipocytes and h/epatoma Huh7 cells. Furthermore, UroC, UroD, and UroA promoted the phosphorylation of AMP-activated protein kinase, suggesting that Uro may alter energy-sensing metabolic pathways in primary human adipocytes. CONCLUSIONS: Taken together, our results demonstrated that UroA, UroC, and UroD, but not isoUroA and UroB, reduce TG accumulation and increase FA oxidation in adipocytes as well as hepatocytes. PMID- 26872563 TI - Is early detection of basal cell carcinoma worthwhile? Systematic review based on the WHO criteria for screening. AB - The incidence of basal cell carcinoma (BCC) has risen three- to fourfold over the last 30 years and is expected to continue to increase with ageing of the population. Although BCC has a good prognosis, it causes significant morbidity and has an important impact on the public health budget due to direct treatment costs. Based on the existing evidence, a systematic evaluation of the World Health Organization criteria was performed to determine whether earlier detection of BCC could reduce morbidity and cost. BCC slowly increases in size, with a median increase in diameter of 0.5 mm over 10 weeks. There is an important delay in diagnosis ranging from 19 to 25 months. In several studies BCC size was the main determinant of treatment cost, surgical complexity, reconstruction technique and the specific surgical procedure performed, such as Mohs micrographic surgery or surgical excision. One study showed that size also seems to affect the cost per treatment for other nonsurgical options. The use of vismodegib, an inhibitor of the hedgehog pathway, is confined to locally advanced or metastatic BCC. Delays in diagnosis and appropriate treatment are the most important underlying causes in the occurrence of giant BCC and/or BCC with metastasis. Although the latter represent only a very small fraction of all BCCs, the majority of them are located in the facial region. The available data point to a slow increase in the size of BCCs over time. Size is one of the major determinants in choice of treatment and the associated cost, especially for facial BCC. Therefore we conclude that current data support early detection and adequate management of BCCs on the face. PMID- 26872564 TI - A study of the prevalence of smear-positive leprosy cases in a tertiary care center in the post-elimination phase of leprosy. AB - BACKGROUND: India has declared leprosy to be eliminated in the country, according to the WHO criteria of attaining a prevalence of less than 1 in 10,000. However, smear-positive leprosy cases are frequently being encountered. METHODS: This is an 18-year retrospective study done in the Department of Dermatology and Venereology, Government Medical College, Trivandrum. Data were collected from the records of all cases in the study period, and the prevalence of smear-positive cases was determined in the post-elimination phase and this was compared to the pre-elimination phase. RESULTS: A total of 901 cases were analyzed, which comprised 538 cases in the pre- and 363 cases in the post-elimination phase. The male/female ratio in the pre and post phases was 2.61 : 1 and 2.45 : 1, respectively. Borderline tuberculoid accounted for the commonest type in both the pre and post phases comprising 45.54 and 50.69%, respectively. Type 2 lepra reactions were seen in 40.21% of the reaction cases in the post-elimination phase. The smear-positive cases in the post-elimination phase accounted for 34.99% compared to 14.68% in the pre-elimination phase. Lepromatous leprosy (LL) accounted for 67.71% of the smear-positive cases in the post phase compared to 67.08% in the pre phase. CONCLUSIONS: There was an increase of 20.30% of smear positive cases in the post-elimination phase, which was statistically significant (P < 0.001), and the majority of them were LL (P < 0.001). PMID- 26872566 TI - Editorial. PMID- 26872565 TI - Conventional testicular sperm extraction (TESE) and non-obstructive azoospermia: is there still a chance in the era of microdissection TESE? Results from a single non-academic community hospital. AB - Spermatozoa can be retrieved in non-obstructive azoospermia (NOA) patients despite the absence of ejaculated spermatozoa in their semen because of the presence of isolated foci with active spermatogenesis. Conventional testicular sperm extraction (c-TESE) in patients with NOA has been partially replaced by micro-TESE. It is still under debate the problem regarding the higher costs related to micro-TESE when compared with c-TESE. In this study, we evaluated sperm retrieval rate (SRR) of c-TESE in naive NOA patients. Sixty-three NOA patients were referred to our centre for a c-TESE. For every subject, we collected demographic data, cause of infertility, time to first infertility diagnosis, serum levels of LH, FSH, total testosterone and prolactin. A statistical analysis was conducted to correlate all the clinical variables, the histology and the Johnsen score with the SRR. Sixty-three consecutive NOA patients with a mean age of 37.3 years were included. The positive SRR was 47.6%. No statistical differences were observed between positive vs. negative SRR regarding mean FSH (17.12 vs. 19.03 mUI/mL; p = 0.72), and LH (9.72 vs. 6.92 mUI/mL; p = 0.39) values. Interestingly, we found a statistically significant difference in terms of time to first infertility diagnosis (+SRR vs. -SRR; 44.5 vs. 57 months; p = 0.02) and regarding to age (+SSR vs. -SRR; 40.1 vs. 35.3; p = 0.04). There was a statistically significant decrease in SRRs with the decline in testicular histopathology from hypospermatogenesis to maturation arrest, and SCO. The mean Johnsen score was 5.9 with a mean percentage of Johnsen score >=8 tubules equal to 19%. The overall pregnancy rate was 26.6%. In our prospective cohort of patients successful SRR with c-TESE was 47.6%. Lower costs and high reproducibility of this technique still support this procedure as an actual reliable option in NOA patients for sperm retrieval. PMID- 26872568 TI - Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014. AB - AIMS: To investigate the link between lower urinary tract symptoms (LUTS) and metabolic disorders. MATERIALS AND METHODS: This report results from presentations and subsequent discussions about LUTS and metabolic disorders at the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, 2014. RESULTS: There are common pathophysiological determinants for the onset of LUTS and the metabolic syndrome (MetS). Both conditions are multifactorial, related to disorders in circadian rhythms and share common risk factors. As in men with erectile dysfunction, these potentially modifiable lifestyle factors may be novel targets to prevent and treat LUTS. The link between LUTS and metabolic disorders is discussed by using sleep, urine production and bladder function as underlying mechanisms that need to be further explored during future research. CONCLUSION: Recent findings indicate a bidirectional relationship between LUTS and the MetS. Future research has to explore underlying mechanisms to explain this relationship, in order to develop new preventive and therapeutic recommendations, such as weight loss and increasing physical activity. The second stage is to determine the effect of these new treatment approaches on the severity of LUTS and each of the components of the MetS. PMID- 26872567 TI - Implications for bidirectional signaling between afferent nerves and urothelial cells-ICI-RS 2014. AB - AIMS: To present a synopsis of the presentations and discussions from Think Tank I, "Implications for afferent-urothelial bidirectional communication" of the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. METHODS: The participants presented what is new, currently understood or still unknown on afferent-urothelial signaling mechanisms. New avenues of research and experimental methodologies that are or could be employed were presented and discussed. RESULTS: It is clear that afferent-urothelial interactions are integral to the regulation of normal bladder function and that its disruption can have detrimental consequences. The urothelium is capable of releasing numerous signaling factors that can affect sensory neurons innervating the suburothelium. However, the understanding of how factors released from urothelial cells and afferent nerve terminals regulate one another is incomplete. Utilization of techniques such as viruses that genetically encode Ca(2+) sensors, based on calmodulin and green fluorescent protein, has helped to address the cellular mechanisms involved. Additionally, the epithelial-neuronal interactions in the urethra may also play a significant role in lower urinary tract regulation and merit further investigation. CONCLUSION: The signaling capabilities of the urothelium and afferent nerves are well documented, yet how these signals are integrated to regulate bladder function is unclear. There is unquestionably a need for expanded methodologies to further our understanding of lower urinary tract sensory mechanisms and their contribution to various pathologies. PMID- 26872569 TI - What is the role of combination drug therapy in the treatment of overactive bladder? ICI-RS 2014. AB - AIMS AND METHODS: The role of combination therapy using oral antimuscarinic medications for the treatment of overactive bladder was proposed at the 2014 International Consultation on Incontinence-Research Society in Bristol, UK to identify key factors to consider when making clinical decisions and to guide future research design. RESULTS: Combination therapy is justified if monotherapy is associated with suboptimal efficacy or bothersome side effects. Combination therapy has the potential to improve efficacy with fewer side effects than monotherapy. Two Phase 2 studies comparing combination therapy that included an antimuscarinic demonstrated improvement in mean voided volume, the primary outcome chosen, with some combinations showing improved micturition frequency and quality of life. The two studies found no evidence of an increased safety risk with combination therapy compared to monotherapy. Future studies should use clinically meaningful or patient reported outcomes such as incontinence episodes when comparing efficacy. If surrogate measures are used, a clear justification should be provided. Cost analyses should be planned for clinical research trials evaluating combination drug therapy. CONCLUSIONS: Combination therapy is reasonable when monotherapy has suboptimal efficacy or bothersome side effects. Future research studies evaluating combination therapy for urgency urinary incontinence should ideally(1) be performed as part of a randomized clinical trial,(2) evaluate non-responders to monotherapy,(3) evaluate combination therapy using medications with different mechanisms of action,(4) include clinically meaningful and patient reported outcomes when evaluating efficacy, and(5) include cost-effectiveness analyses to justify any increased cost by showing improvement in efficacy or reduction in side effects. PMID- 26872570 TI - Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder? ICI-RS 2014. AB - AIMS: The use of botulinum toxin A (BoNT/A) is commonplace now in the management of refractory overactive bladder and neurogenic detrusor overactivity (NDO). Despite one formulation now having a license, the full mechanism of action is not fully understood. Furthermore practice varies worldwide in the way the toxin is delivered to the bladder. At the ICI-RS 2014 Meeting in Bristol, UK a Think Tank session was conducted on the topic of "Do we understand how botulinum toxin works and have we optimized the way it is administered to the bladder?" This manuscript reflects the Think Tank's summary and opinion. METHODS: An overview of the existing evidence and consensus regarding mechanism of action and practical aspects of BoNT/A administration was presented. Further avenues of potential research were suggested. RESULTS: BoNT/A effect in the bladder is complex with likely effects on both efferent and afferent nerves. The site of action is controversial with the relative contribution of the detrusor as opposed to the suburothelial effects remaining unclear and open to further studying. The classical concept of prevention of acetylcholine release in the bladder is not supported by a wealth of evidence on neurotransmitters although co-localization studies have suggested cholinergic nerves are the most affected by BoNT/A. There is more robust evidence for effects on the purinergic system and afferent desensitization and emerging evidence for central effects. A variety of technique studies were presented. OnabotlinumtoxinA has recently been studied in large phase III trials and with this there is a standardized injection technique which is trigone-sparing. The evidence for altering location of injection is mixed with some studies suggesting less voiding dysfunction in bladder base injections alone but others suggesting location of injection does not affect outcomes. Early pilot data and evidence of instillation either with electromotive drug administration (EMDA) or in liposomes were also presented as an alternative to injections. CONCLUSIONS: The mechanism of action of BoNT/A in the bladder is complex and not fully understood. There is emerging support for its role on afferent mechanisms. The technical aspects of the injection procedure have been standardized to a certain extent but further study is required in larger scale studies to assess minimizing voiding dysfunction, improving tolerability, and assessing alternatives to injections. PMID- 26872572 TI - Do we manage incontinence in children and adults with special needs adequately? ICI-RS 2014. AB - AIMS: To review studies on the associations of incontinence and special needs in children and adults and to outline future directions in research and clinical care. MATERIALS AND METHODS: A review of literature was conducted. Open questions and future directions were discussed during the ICI-RS meeting in 2014. RESULTS: Special needs comprise a wide variety of conditions and disabilities. Individuals with special needs carry a greater risk for all types of incontinence. There is a high tendency for incontinence to persist from childhood into adulthood. Many people do not receive adequate medical care for their incontinence. CONCLUSIONS: More detailed research is needed, especially in the adult population with special needs. Assessment and treatment of incontinence should be offered routinely to all those with special needs. PMID- 26872571 TI - Do we need to know more about the effects of hormones on lower urinary tract dysfunction? ICI-RS 2014. AB - This review article reflects the presentations and subsequent discussions during a think tank at the 5th International Consultation on Incontinence Research Society's annual meeting, held in Bristol, UK (September 22-24, 2014). It reviews the current state of knowledge on the role of hormones in lower urinary tract dysfunction (LUTD) and overactive bladder (OAB) and in particular: highlights some specific basic research findings from discussion participants; reviews future research topics; and discusses potential new therapeutic opportunities for LUTD and OAB. The role of the large conductance voltage- and Ca(2+) -activated K(+) (BK) channels, as novel therapeutic targets for OAB was discussed, in particular as recent studies on human detrusor smooth muscle suggest that estradiol exerts a direct non-genomic activation of the BK channels. Recent developments on the roles of sex hormones on diuresis, as well as the roles of melatonin and vitamin D on LUTD were also discussed. It was concluded that further basic science and translational studies are needed to better understand hormonal regulatory mechanisms of the lower urinary tract and the implications for novel treatment options for LUTD and OAB. PMID- 26872573 TI - Recommendations for future development of contractility and obstruction nomograms for women. ICI-RS 2014. AB - AIMS: At present, existing bladder outlet obstruction (BOO) nomograms for women are still not universally accepted. Moreover, only limited information is available regarding bladder contractility in women. The aim is to present the discussions and recommendations from the think tank session "Can we construct and validate contractility and obstruction nomograms for women?" held at the 2014 International Consultation on Incontinence-Research Society (ICI-RS) meeting in Bristol, UK. METHODS: An overview of clinical significance, bladder mechanics and modelling, lack of existing nomograms for women, and development of new nomograms were presented and discussed in a multidisciplinary think tank session. This think tank session was based on a collaboration between physicians, engineers, and researchers and consensus was achieved on future research initiatives. RESULTS AND CONCLUSIONS: Based on the think tank discussion, the ICI-RS panel put forward the following recommendations: the need to acquire normative age-matched data in women to define "normal" and "pathological" values of urodynamic parameters; the inclusion of additional clinical data in new nomograms and the use of this extra dimension to develop clinically applicable nomograms for female BOO and contractility; and finally, the need to take into account the variability of BOO in women when developing female bladder contractility nomograms. PMID- 26872574 TI - Detrusor underactivity and the underactive bladder: Symptoms, function, cause what do we mean? ICI-RS think tank 2014. AB - Impaired bladder emptying is a well-recognized cause of lower urinary tract symptoms. However, the symptoms produced do not always relate to voiding, and may include frequency, urgency and incontinence. Conversely, the etiology of symptoms of disturbed voiding is not necessarily dependent upon objectively impaired voiding. Terms including underactive bladder, detrusor underactivity, and impaired contractility describe aspects of these problems, and have been used somewhat interchangeably. It is possible that the present lack of effective therapy in many cases relates to both etiologic and diagnostic uncertainty stemming from terminologic imprecision. Detrusor underactivity has a standardized definition, unlike underactive bladder and impaired contractility. The relationships of symptoms, function, and cause were the focus of a 2014 ICI-RS Think Tank entitled Does Detrusor Underactivity Exist, and if so it is neurogenic, myogenic, or both? This review presents a summary of the problem and the Think Tank conclusions. A terminologic hierarchy and specific research goals are presented. PMID- 26872575 TI - Fundamentals and clinical perspective of urethral sphincter instability as a contributing factor in patients with lower urinary tract dysfunction--ICI-RS 2014. AB - AIMS: Urethral pathophysiology is often neglected in discussions of bladder dysfunction. It has been debated whether "urethral sphincter instability," referred to based on observed "urethral pressure variations," is an important aspect of overactive bladder syndrome (OAB). The purpose of this report is to summarize current urethral pathophysiology evidence and outline directions for future research based on a literature review and discussions during the ICI-RS meeting in Bristol in 2014. METHODS: Urethral pathophysiology with a focus on urethral pressure variation (UPV) was presented and discussed in a multidisciplinary think tank session at the ICI_R meeting in Bristol 2014. This think tank session was based on collaboration between physicians and basic science researchers. RESULTS: Experimental animal studies or studies performed in clinical series (predominantly symptomatic women) provided insights into UPV, but the findings were inconsistent and incomplete. However, UPV is certainly associated with lower urinary tract symptoms (likely OAB), and thus, future research on this topic is relevant. CONCLUSIONS: Future research based on adequately defined clinical (and urodynamic) parameters with precisely defined patient groups might shed better light on the cause of OAB symptoms. Further fundamental investigation of urethral epithelial-neural interactions via the release of mediators should enhance our knowledge and improve the management of patients with OAB. PMID- 26872577 TI - Re: Anding R, Smith P, Gammie A, Thiruchelvam N, Arlandis S, Giarenis I, Rantell A, Cardozo L, Rosier P. When should video be added to conventional urodynamics in adults and is it justified by the evidence? ICI-RS 2014. neurourol urodyn 2015. PMID- 26872576 TI - When should video be added to conventional urodynamics in adults and is it justified by the evidence? ICI-RS 2014. AB - AIMS: To debate and evaluate the evidence base regarding the added value of video to urodynamics in adults and to define research questions. METHODS: In the ICI-RS Meeting 2014 a Think Tank analyzed the current guidelines recommending video urodynamics (VUD) and performed a literature search to determine the level of evidence for the additional value of the imaging with urodynamic assessment of both neurogenic and non-neurogenic lower urinary tract dysfunction. RESULTS: Current guidelines do not specify the added value of imaging to urodynamics. Recommendations are based on single center series and expert opinion. Standard imaging protocols are not available and evidence regarding the balance between number and timing of pictures, patient positioning, and exposure time on the one hand and diagnosis on the other hand is lacking. On the basis of expert consensus VUD is relevant in the follow-up of patients with spinal dysraphism. Evidence for the value of VUD in non-neurogenic lower urinary tract dysfunction is sparse. There is some evidence that VUD is not necessary in uncomplicated female SUI, but expert opinion suggests it might improve the evaluation of patients with recurrent SUI. CONCLUSIONS: There is only low level evidence for the addition of video to urodynamics. The ICI-RS Think Tank encourages better reporting of results of imaging and systematic reporting of X-ray doses. Specific research hypotheses regarding the added value of imaging are recommended. The panel suggests the development of standards for technically optimal VUD that is practically achievable with machines that are on the market. PMID- 26872578 TI - When should video and EMG be added to urodynamics in children with lower urinary tract dysfunction and is this justified by the evidence? ICI-RS 2014. AB - AIMS: An ICI-RS Think Tank in 2014 discussed and evaluated the evidence for adding video and EMG to urodynamics (UDS) in children and also highlighted evidence gaps, with the aim of recommending further clinical and research protocols. METHODS: A systematic analysis of the relevant literature for both X ray (video) studies and electromyography, in combination with UDS in children with lower urinary tract dysfunction (LUTD), is summarized in this manuscript. The technical aspects are also critically reviewed. RESULTS: The body of evidence for the addition of X-ray (video) to filling and voiding cystometry and the evidence for the addition of pelvic muscle surface electromyography to urodynamics is scanty and insufficient. Standards are poor and variable so uncontrolled expert opinion dominates practice. CONCLUSIONS: The Think Tank has recommended that standardized ALARA ("As Low As Reasonably Achievable") principles should be adopted for video-urodynamics in children. The risk-benefit balance of X-ray exposure needs to be better evaluated and defined. Evaluation of images should be standardized and the association with pressure changes better analyzed and reported. Children's pelvic muscle surface electromyography technique should be standardized, technically improved, and its diagnostic relevance should be better evaluated. PMID- 26872579 TI - Does long-term profound inhibition of gastric acid secretion increase the risk of ECL cell-derived tumors in man? AB - OBJECTIVE: Since the description of ECL cell-derived tumors in rodents after long term profound acid inhibition inducing hypergastrinemia, there has been concern that proton pump inhibitors (PPIs) could also do that in man. The recent description of a Spanish family with gastric ECL cell tumors at the age of about 30 years secondary to a defect in the proton pump due to mutation in the ATP4A gene clearly shows that hypergastrinemia alone also is sufficient to induce ECL cell neoplasia in man. The present review aims to evaluate the risk of gastric neoplasia secondary to gastric acid inhibition. METHODS: Literature (MEDLINE) was searched for the role of the ECL cell in gastric carcinogenesis in animals and man in general and particularly secondary to long-term inhibition of acid secretion. RESULTS: An important proportion of patients treated with PPI develops hypergastrinemia causing ECL cell hyperplasia and the first descriptions of ECL cell carcinoids secondary to PPI have been reported. The role of the ECL cell has hitherto been under estimated in gastric carcinogenesis in man where for instance the signet ring cell type of gastric carcinoma seems to originate from the ECL cell. CONCLUSIONS: The first two of three steps in rodent ECL cell carcinogenesis (hyperplasia, carcinoid, and carcinoma) secondary to PPI dosing, have been described for man. It is every reason to believe that the final step, gastric carcinoma, will develop also in man. Clinical decisions should be based not only on so-called evidence based medicine, but also on physiological knowledge and animal studies. PMID- 26872580 TI - Morphological and chemical changes of aerosolized E. coli treated with a dielectric barrier discharge. AB - This study presents the morphological and chemical modification of the cell structure of aerosolized Escherichia coli treated with a dielectric barrier discharge (DBD). Exposure to DBD results in severe oxidation of the bacteria, leading to the formation of hydroxyl groups and carbonyl groups and a significant reduction in amine functionalities and phosphate groups. Near edge x-ray absorption fine structure (NEXAFS) measurements confirm the presence of additional oxide bonds upon DBD treatment, suggesting oxidation of the outer layer of the cell wall. Electron microscopy images show that the bacteria undergo physical distortion to varying degrees, resulting in deformation of the bacterial structure. The electromagnetic field around the DBD coil causes severe damage to the cell structure, possibly resulting in leakage of vital cellular materials. The oxidation and chemical modification of the bacterial components are evident from the Fourier transform infrared spectroscopy and NEXAFS results. The bacterial reculture experiments confirm inactivation of airborne E. coli upon treating with DBD. PMID- 26872581 TI - In vitro hemocompatibility testing: The importance of fresh blood. AB - The use of unactivated blood for hemocompatibility testing is essential to obtain reliable results. Here, the authors study the influence of heparinized whole blood storage time and temperature on blood activation and evaluate the importance of initiating hemocompatibility tests within 4 h of blood collection. Blood from healthy volunteers was collected and analyzed with minimal delay, after 30 min and after 60 min of storage at room temperature, 30 or 37 degrees C. In addition, blood was analyzed after 1, 2, or 4 h of storage at room temperature. Platelet count, mean platelet volume, platelet binding capacity to collagen and thromboxane B2 were measured to assess platelet function, complement complex C5b-9 and elastase were measured to assess activation of the inflammatory response system, and thrombin-antithrombin III was measured to assess activation of the coagulation system. Furthermore, free hemoglobin was measured in platelet poor plasma as an indicator for red blood cell damage. The authors found that storage at 30 degrees C significantly increased platelet and coagulation activity after 60 min and storage at 37 degrees C significantly increased platelet, coagulation, and white blood cell activity after 60 min. Storage at room temperature significantly decreased platelet binding to collagen after 4 h and increased platelet activity after 1 h onward and white blood cell activity after 4 h. Their results show that short-term storage of heparinized whole blood significantly influences biomarkers over time, especially at 30 and 37 degrees C compared to room temperature. However, blood stored at room temperature for 4 h is also affected. In particular, platelet function and white blood cell activity are significantly influenced after 4 h of stationary storage at room temperature; therefore, the authors propose that hemocompatibility tests should be initiated well within 4 h of blood collection, preferably within 2 h. PMID- 26872583 TI - A facile sonochemical route for the synthesis of MoS2/Pd composites for highly efficient oxygen reduction reaction. AB - For the alkaline fuel cell cathode reaction, it is very essential to develop novel catalysts with superior catalytic properties. Here, we report the synthesis of highly active and stable MoS2/Pd composites for the oxygen reduction reaction (ORR), via a simple, eco-friendly sonochemical method. The bulk MoS2 was first transformed into single and few layers MoS2 nanosheets through ultrasonic exfoliation. Then the exfoliated MoS2 nanosheets served as supporting materials for the nucleation and further in-situ growth of Pd nanoparticles to form MoS2/Pd composites via ultrasonic irradiation. Cyclic voltammetry and rotating disk voltammetry measurements demonstrate that as-prepared MoS2/Pd composites which provides a direct four-electron pathway for the ORR, have better electrocatalytic activity, long-term operation stability than commercial Pt/C catalyst. We expect that the present work would provide a promising strategy for the development of efficient oxygen reduction electrocatalyst. In addition, this study can also be extended to the preparation of other hybrid with desirable morphologies and functions. PMID- 26872582 TI - Quantifying element incorporation in multispecies biofilms using nanoscale secondary ion mass spectrometry image analysis. AB - Elucidating nutrient exchange in microbial communities is an important step in understanding the relationships between microbial systems and global biogeochemical cycles, but these communities are complex and the interspecies interactions that occur within them are not well understood. Phototrophic consortia are useful and relevant experimental systems to investigate such interactions as they are not only prevalent in the environment, but some are cultivable in vitro and amenable to controlled scientific experimentation. Nanoscale secondary ion mass spectrometry (NanoSIMS) is a powerful, high spatial resolution tool capable of visualizing the metabolic activities of single cells within a biofilm, but quantitative analysis of the resulting data has typically been a manual process, resulting in a task that is both laborious and susceptible to human error. Here, the authors describe the creation and application of a semiautomated image-processing pipeline that can analyze NanoSIMS-generated data, applied to phototrophic biofilms as an example. The tool employs an image analysis process, which includes both elemental and morphological segmentation, producing a final segmented image that allows for discrimination between autotrophic and heterotrophic biomass, the detection of individual cyanobacterial filaments and heterotrophic cells, the quantification of isotopic incorporation of individual heterotrophic cells, and calculation of relevant population statistics. The authors demonstrate the functionality of the tool by using it to analyze the uptake of (15)N provided as either nitrate or ammonium through the unicyanobacterial consortium UCC-O and imaged via NanoSIMS. The authors found that the degree of (15)N incorporation by individual cells was highly variable when labeled with (15)NH4 (+), but much more even when biofilms were labeled with (15)NO3 (-). In the (15)NH4 (+)-amended biofilms, the heterotrophic distribution of (15)N incorporation was highly skewed, with a large population showing moderate (15)N incorporation and a small number of organisms displaying very high (15)N uptake. The results showed that analysis of NanoSIMS data can be performed in a way that allows for quantitation of the elemental uptake of individual cells, a technique necessary for advancing research into the metabolic networks that exist within biofilms with statistical analyses that are supported by automated, user-friendly processes. PMID- 26872585 TI - Comparison of Gait Motion Including Postoperative Trunk Deflection Between Direct Lateral and Anterolateral Approaches in Supine Total Hip Arthroplasty. AB - BACKGROUND: A prospective study was conducted to compare the effect of an anterolateral approach in the supine position (ALS) with that of a direct lateral (DL) approach on gait motion, including trunk deflection, in walking after total hip arthroplasty. We hypothesized that trunk deflection in walking after ALS would be significantly improved in comparison with use of the DL approach. METHODS: The subjects were 15 patients, with 7 in the ALS group and 8 in the DL group. Walking before and 9 and 28 weeks after surgery was analyzed using 3 dimensional motion analysis. RESULTS: Walking velocity, stride length, hip joint range of motion in the sagittal plane in walking, and locomotion range of trunk inclination were significantly improved 28 weeks after surgery in both groups. In gait analysis, there were no significant differences between the 2 groups. CONCLUSION: This study was conducted to compare the effect of ALS with that of a DL approach on locomotion in walking after total hip arthroplasty. Hip pain at 9 weeks after surgery was significantly improved using ALS compared to the DL approach, but there were no significant differences in gait function at 28 weeks after surgery using ALS or DL approach. Further long-term studies are required to examine differences between these procedures. PMID- 26872584 TI - Liposomal Bupivacaine as an Adjunct to Postoperative Pain Control in Total Hip Arthroplasty. AB - BACKGROUND: Although pain management affects rehabilitation, length of stay, and functional outcome, an optimized pain management protocol has yet to be standardized. Opioids are the primary agent used to control acute postoperative pain; however, they are associated with a wide range of side effects. Liposomal bupivacaine (LB), a long-acting analgesic agent administered intraoperatively, has been introduced as a new modality to control pain for up to 72 hours after operation without affecting motor function. METHODS: Six hundred eighty-six primary total hip arthroplasty (THA) patients, who received the standard THA pain management protocol, were compared to a cohort of 586 primary THA patients, who were treated with an additional intraoperative injection of LB. All other pain management parameters and standard of care were identical. Statistical significance was set at P <= .05. RESULTS: Although patient-reported pain scores were statistically similar, the LB cohort demonstrated a significant decrease in total narcotic use (P < .001), specifically up to postoperative day 2 (P = .016). Physical therapy milestones were significantly achieved to a greater degree (P < .001) in the LB cohort. Operation time and hospital cost were unaffected (P = .072 and .811, respectively); however, the LB cohort exhibited a decrease in length of stay by 0.31 days (P < .001) and improvement in discharge disposition to home (P = .017). CONCLUSION: LB is a valuable adjunct to our THA pain management protocol, as we strive to achieve improved patient outcomes, reductions in length of stay, and enhanced quality of THA care. PMID- 26872587 TI - Barbed Suture Is Associated With Increased Risk of Wound Infection After Unicompartmental Knee Arthroplasty. AB - BACKGROUND: Literature addressing the risks of barbed suture in arthroplasty remains limited. No study to our knowledge has compared rates of wound infection between barbed and conventional suture after unicompartmental knee arthroplasty (UKA). We hypothesized that barbed suture would be associated with an increased risk of wound infection in patients undergoing UKA. METHODS: Electronic records were retrieved for 1040 UKA procedures. Odds ratios with postoperative wound infection as the outcome and barbed suture as the exposure were calculated. Binary logistic regression corrected for age, gender, body mass index, operative time, and risk factors (smoking, diabetes, renal insufficiency, and immunosuppression). Barbed suture consisted of Quill #2 polydioxanone (or #0 Vicryl) for deep closure and Quill 2-0 Monoderm for subcuticular closure. Conventional suture consisted of #0 Vicryl for deep closure and subcuticular 2-0 Monocryl or staples for skin closure. RESULTS: A total of 839 procedures were included. Barbed suture was used in 333 surgeries, and conventional suture was used in 506. Eight cases of postoperative wound infection were identified. All infections occurred in the barbed suture cohort. Regression analysis revealed an association between subcuticular barbed suture and postoperative wound infection (odds ratio = 22.818, confidence interval = 2.69-2923.91; P = .0074). CONCLUSIONS: The findings indicate that the use of barbed suture in subcuticular layer closure is associated with an increased risk of wound infection. This may be exacerbated by early intensive mobilization, commonly undertaken after UKA to permit rapid functional return. We recommend against the use of barbed suture for subcuticular layer closure in UKA. PMID- 26872586 TI - Cemented Total Hip Arthroplasty With Retrograde Ischioacetabular Steinmann Pin Reconstruction for Periacetabular Metastatic Carcinoma. AB - BACKGROUND: Surgical management of advanced periacetabular lesions is challenging because of extensive bone loss, particularly for Modified American Academy of Orthopaedic Surgeons Classification defects type IV (pelvic discontinuity with posterior column involvement). Multiple methods for rebuilding the acetabulum have been described; all involve passing Steinmann pins in a retrograde or an antegrade fashion from the anterior iliac wing or iliac crest around the acetabulum in an attempt to recreate the normal bony anatomy. However, these techniques fail to engage the ischium in its entirety. The ischial contribution to the posterior column is a critical element in a stable acetabular construct. METHODS: After curettage of the acetabular lesion, Steinmann pins are passed through the ischial tuberosity and posterior column into the sciatic buttress in a retrograde manner. The number of pins depends on the size of the defect and involvement of the posterior column. PATIENTS AND METHODS: Medical records of 11 patients with a Modified American Academy of Orthopaedic Surgeons Classification defect type IV treated with retrograde ischioacetabular Steinmann pin reconstruction at our institution between 2007 and 2012 were reviewed. European Quality of Life-5 dimensions and Lower Extremity Functional Scale questionnaires were used to assess patient functional outcomes. RESULTS: The 6 patients (4 females and 2 males; age range, 56-81 years) surviving 12 months postoperatively reported improved mobility and good quality-of-life scores. CONCLUSION: We described a new method for posterior acetabular column reconstruction that uses the ischial tuberosity and body as additional points of stabilization during the reconstruction of the posterior column. PMID- 26872588 TI - Cavity with ball-in-hole lesion in the lung. PMID- 26872590 TI - Knee Kinematics and Joint Moments During Stair Negotiation in Participants With Anterior Cruciate Ligament Deficiency and Reconstruction: A Systematic Review and Meta-Analysis. AB - OBJECTIVE: Biomechanical changes have been reported for patients with anterior cruciate ligament deficiency (ACLD) and anterior cruciate ligament (ACL reconstruction) (ACLR), likely due to loss of stability and changes in proprioception and neuromotor control. This review evaluated kinematics and kinetics of ACLD and ACLR knees, compared with those on the contralateral uninjured sides, as well as and those in asymptomatic controls during stair navigation. DESIGN: This is a systematic review and meta-analysis. LITERATURE SURVEY: Electronic database searches were conducted from their original available dates to January 2015. Studies that included participants with ACLD or ACLR and reported knee joint angles or moments during stair ascent or descent were included. METHODOLOGY: Nine studies met the inclusion criteria, and the methodological quality of these was assessed with a modified Downs and Black checklist. Effect sizes for differences between injured leg and uninjured contralateral leg or controls were calculated, and meta-analyses were performed if two or more studies considered the same variable. SYNTHESIS: Quality assessment showed an average (+/- standard deviation) of 70.3% +/- 7.2%. Meta analysis showed less knee flexion at initial contact for ACLR knees compared with that in contralateral knees during stair ascent, with a moderate effect size and minimal heterogeneity. Knees with ACLD showed less peak knee flexion compared with that on contralateral sides during stair ascent, with minimal heterogeneity. External knee flexion moments were lower for ACLR compared with those in controls and contralateral sides during ascent and descent, whereas these moments were decreased for the ACLD compared with controls only during ascent. Meta-analysis results exhibited moderate/high heterogeneity or small/trivial effect sizes. CONCLUSIONS: Differences for kinematics and kinetics for the ACL-injured knees indicate long-term compensatory and asymmetric movement patterns while ascending and descending stairs. Due to the heterogeneity as well as the small numbers of available studies, the consequences of these differences in terms of long-term function or posttraumatic osteoarthritis need further exploration. PMID- 26872591 TI - A Case for Nephron Sparing Surgery in the Management of Upper Tract Urothelial Carcinoma. AB - Upper tract urothelial carcinoma (UTUC) is rare and its management presents many challenges. Outside of distal ureterectomy for select cases, management has been primarily radical nephroureterectomy. Endoscopic nephron sparing management (NSM) is recognized to have some role in UTUC treatment; however, it is yet to gain firm footing in the treatment algorithm. In this review, we discuss the benefits of NSM with regards to oncologic outcomes, renal function preservation, and cost savings. Finally, we propose recognition of endoscopic NSM as a first-line treatment in selected patients with low risk disease. PMID- 26872589 TI - Influence of Menstrual Cycle and Oral Contraceptive Phase on Spinal Excitability. AB - BACKGROUND: Rates of musculoskeletal injury differ substantially between the genders, with females more likely to experience conditions such as anterior cruciate ligament (ACL) injuries than males in the same sports. Emerging evidence suggests a significant hormonal contribution. Most research has focused solely on how hormonal fluctuations affect connective tissue, but a direct link between hormonal shifts, ligamentous laxity, and ACL injury has not been borne out. There is also evidence to suggest that sex hormones can modulate the central nervous system, but how this affects neuromuscular control is not well understood. OBJECTIVE: To determine whether changes in sex hormone concentrations would alter spinal excitability, measured across the menstrual and oral contraceptive pill cycle. We hypothesized that spinal excitability would fluctuate across the menstrual cycle (with increased excitability during the periovulatory phase due to peak estradiol concentration), but that there would be no fluctuation in oral contraceptive users. DESIGN: This was a prospective cohort study. SETTING: The study took place at a biomechanics laboratory at a rehabilitation hospital. PARTICIPANTS: A total of 30 healthy women aged 18-35 who were similar in age, body composition, and exercise-training status were included. Fifteen of the women were eumenorrheic and nonusers of oral contraceptives (nonusers), and 15 of the women were taking oral contraceptives (users). MAIN OUTCOME MEASURES: H reflex (Hmax/Mmax ratio), serum estradiol, and progesterone concentrations were measured at 3 time points during the menstrual and contraceptive pill cycle. RESULTS: The H-reflex (Hmax/Mmax ratio) remained stable across the menstrual and contraceptive pill cycle. Spinal excitability was lower in the users compared with the nonusers across all testing sessions, but this was not statistically significant. CONCLUSIONS: Our results suggest that acute fluctuations of endogenous estradiol and progesterone do not modulate spinal excitability. However, long-term exposure to exogenous estrogen and progesterone (oral contraceptives) might have an impact on spinal excitability and neuromuscular control. Further research is necessary to better understand the potential differential effect of endogenous and exogenous sex hormones on spinal excitability. PMID- 26872592 TI - Environmental stimulation rescues maternal high fructose intake-impaired learning and memory in female offspring: Its correlation with redistribution of histone deacetylase 4. AB - Impairment of learning and memory has been documented in the later life of offspring to maternal consumption with high energy diet. Environmental stimulation enhances the ability of learning and memory. However, potential effects of environmental stimulation on the programming-associated deficit of learning and memory have not been addressed. Here, we examined the effects of enriched-housing on hippocampal learning and memory in adult female offspring rats from mother fed with 60% high fructose diet (HFD) during pregnancy and lactation. Impairment of spatial learning and memory performance in HFD group was observed in offspring at 3-month-old. Hippocampal brain-derived neurotrophic factor (BDNF) was decreased in the offspring. Moreover, the HFD group showed an up-regulation of histone deacetylase 4 (HDAC4) in the nuclear fractions of hippocampal neurons. Stimulation to the offspring for 4weeks after winning with an enriched-housing environment effectively rescued the decrease in cognitive function and hippocampal BDNF level; alongside a reversal of the increased distribution of nuclear HDAC4. Together these results suggest that later life environmental stimulation effectively rescues the impairment of hippocampal learning and memory in female offspring to maternal HFD intake through redistributing nuclear HDAC4 to increase BDNF expression. PMID- 26872593 TI - Pattern separation and pattern completion in the hippocampal system. Introduction to the Special Issue. PMID- 26872594 TI - Working memory performance inversely predicts spontaneous delta and theta-band scaling relations. AB - Electrophysiological studies have strongly implicated theta-band activity in human working memory processes. Concurrently, work on spontaneous, non-task related oscillations has revealed the presence of long-range temporal correlations (LRTCs) within sub-bands of the ongoing EEG, and has begun to demonstrate their functional significance. However, few studies have yet assessed the relation of LRTCs (also called scaling relations) to individual differences in cognitive abilities. The present study addressed the intersection of these two literatures by investigating the relation of narrow-band EEG scaling relations to individual differences in working memory ability, with a particular focus on the theta band. Fifty-four healthy adults completed standardized assessments of working memory and separate recordings of their spontaneous, non-task-related EEG. Scaling relations were quantified in each of the five classical EEG frequency bands via the estimation of the Hurst exponent obtained from detrended fluctuation analysis. A multilevel modeling framework was used to characterize the relation of working memory performance to scaling relations as a function of general scalp location in Cartesian space. Overall, results indicated an inverse relationship between both delta and theta scaling relations and working memory ability, which was most prominent at posterior sensors, and was independent of either spatial or individual variability in band-specific power. These findings add to the growing literature demonstrating the relevance of neural LRTCs for understanding brain functioning, and support a construct- and state-dependent view of their functional implications. PMID- 26872595 TI - Flow cytometric characterization of microglia in the offspring of PolyI:C treated mice. AB - The neuropathology of schizophrenia has been reported to be closely associated with microglial activation. In a previous study, using the prenatal PolyI:C schizophrenia animal model, we showed an increase in cell numbers and a reduction in microglial branching in 30-day-old PolyI:C descendants, which suggests that there is microglial activation during adolescence. To provide more information about the activation state, we aimed to examine the expression levels of Iba1, which was reported to be up-regulated in activated microglia. We used a flow cytometric approach and investigated CD11b and CD45, two additional markers for the identification of microglial cells. We demonstrated that intracellular staining against Iba1 can be used as a reliable flow cytometric method for identification of microglial cells. Prenatal PolyI:C treatment had long-term effects on CD11b and CD45 expression. It also resulted in a trend towards increased Iba1 expression. Imbalance in CD11b, CD45, and Iba1 expression might contribute to impaired synaptic surveillance and enhanced activation/inflammatory activity of microglia in adult offspring. PMID- 26872596 TI - Mitochondrial specific therapeutic targets following brain injury. AB - Traumatic brain injury is a complicated disease to treat due to the complex multi factorial secondary injury cascade that is initiated following the initial impact. This secondary injury cascade causes nonmechanical tissue damage, which is where therapeutic interventions may be efficacious for intervention. One therapeutic target that has shown much promise following brain injury are mitochondria. Mitochondria are complex organelles found within the cell. At a superficial level, mitochondria are known to produce the energy substrate used within the cell called ATP. However, their importance to overall cellular homeostasis is even larger than their production of ATP. These organelles are necessary for calcium cycling, ROS production and play a role in the initiation of cell death pathways. When mitochondria become dysfunctional, they can become dysregulated leading to a loss of cellular homeostasis and eventual cell death. Within this review there will be a deep discussion into mitochondrial bioenergetics followed by a brief discussion into traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. The review will conclude with a discussion pertaining to the therapeutic approaches currently being studied to ameliorate mitochondrial dysfunction following brain injury. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26872598 TI - Role of gap junctions on synchronization in human neocortical networks. AB - Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ. In the present study, we have investigated the effects of GAP-134, a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue. To delineate the impact of GJ on spatial spread of synchronous activity we evaluated the effects of carbenoxolone (CBX, a non selective GJ blocker) on the spread in three axes 1. vertically in a given cortical column, 2. laterally within the deep cortical layers and 3. laterally within the upper cortical layers. GAP-134 slightly increased the frequency of the 4AP-induced spontaneous epileptiform activities while leaving the PUI unaffected. CBX had no effect on the PUI within a cortical column or on the PUI in the deep cortical layers. CBX increased the PUI for long interelectrodes distances in the upper cortical layers. In conclusion we provide new arguments toward the role played by glial GJ to maintain the frequency of spontaneous activities. We show that neuronal GJ control the PUI only in upper cortical layers. PMID- 26872599 TI - Plasminogen-Dependent Matriptase Activation Accelerates Plasmin Generation by Differentiating Primary Human Keratinocytes. AB - Pericellular plasmin generation, an important pathophysiological process, can be initiated and accelerated by the autoactivation of the type 2 transmembrane serine protease matriptase and subsequent activation of urokinase plasminogen activator. The link between matriptase and plasminogen was initially thought to be one-directional: from matriptase, through plasminogen activator, to plasminogen. However, in the current study, we now show that primary human keratinocytes that are undergoing calcium-induced differentiation can rapidly activate matriptase in response to serum treatment via a mechanism dependent on intracellular calcium, protein kinase C, and phosphatidylinositol 3-kinases-based signaling. The serum factor, responsible for the induction of matriptase zymogen activation, was shown to be plasminogen. A sub-pM concentration of plasminogen (but not plasmin) acting at the cell surface is sufficient to induce matriptase activation, suggesting high potency and specificity of the induction. After matriptase zymogen activation, a proportion of active matriptase is shed into extracellular milieu and returns to the cell surface to accelerate plasmin generation. The ability of plasminogen to induce matriptase zymogen activation and the subsequent acceleration of plasmin generation by active matriptase reveals a feed-forward mechanism that allows differentiating human keratinocytes to rapidly and robustly activate pericellular proteolysis. PMID- 26872601 TI - DUX4 Is Derepressed in Late-Differentiating Keratinocytes in Conjunction with Loss of H3K9me3 Epigenetic Repression. PMID- 26872600 TI - Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma. AB - Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sezary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR. Importantly, in early stage MF, MTAP loss occurred independently of CDKN2A loss in 37% of samples. In peripheral blood mononuclear cells from patients with SS, codeletion with CDKN2A occurred in 18% of samples but loss of MTAP alone was uncommon. In CD4(+) cells from SS, reduced MTAP mRNA expression correlated with MTAP copy number loss (P < 0.01) but reduced MTAP expression was also detected in the absence of copy number loss. Deep sequencing of MTAP/CDKN2A-CDKN2B loci in 77 peripheral blood mononuclear cell DNA samples from patients with SS did not show any nonsynonymous mutations, but read-depth analysis suggested focal deletions consistent with MTAP and CDKN2A copy number loss detected with quantitative reverse transcription PCR. In a cutaneous T-cell lymphoma cell line, promoter hypermethylation was shown to downregulate MTAP expression and may represent a mechanism of MTAP inactivation. In conclusion, our findings suggest that there may be selection in early stages of MF for MTAP deletion within the cutaneous tumor microenvironment. PMID- 26872602 TI - The Alarmin IL-33 Derived from HSV-2-Infected Keratinocytes Triggers Mast Cell Mediated Antiviral Innate Immunity. PMID- 26872603 TI - Monosodium Urate Crystals Induce Functional Expression of P2Y14 Receptor in Human Keratinocytes. PMID- 26872604 TI - Rab11a Is Essential for Lamellar Body Biogenesis in the Human Epidermis. AB - Most of the skin barrier function is attributable to the outermost layer of the epidermis, the stratum corneum, which is composed of flattened, anucleated cells called corneocytes surrounded by a lipid-enriched lamellar matrix. The composition of the stratum corneum is directly dependent on the underlying granular keratinocytes, which are the last living cells in the stratified epidermis. Many components present in the intercorneocyte matrix are delivered by the underlying granular keratinocytes through a secretion process dependent on lysosome-related organelles called lamellar bodies. Because of the importance of lamellar bodies in the maintenance of the epidermal barrier, the mechanisms regulating their biogenesis must be better understood. In this study, we show that the Rab11a GTPase is highly expressed in terminally differentiated keratinocytes, where it is partly associated with lamellar bodies. Rab11a silencing in three-dimensional in vitro reconstructed human epidermis induces a barrier defect, a decrease in the amount of lipid found in the stratum corneum, a reduction in lamellar body density and secretion areas in granular keratinocytes, and the mis-sorting of lamellar body cargoes being driven to the lysosomal degradation pathway. Our results highlight the importance of Rab11a-dependent regulation of lamellar body biogenesis in keratinocytes and consequently on epidermal barrier homeostasis. PMID- 26872605 TI - In the home of the oculist (ABC, 1918). PMID- 26872606 TI - A Cross-Docking Study on Matrix Metalloproteinase Family. AB - BACKGROUND: Matrix metalloproteinases (MMPs) contribute to various physiological and pathophysiological processes. An imbalance in MMP activity causes pathological conditions including inflammatory diseases, cancer, and cardiovascular diseases. Each MMP member has many 3D structures available; therefore, selecting one structure for virtual screening becomes challenging. METHODS: In this study, we used the cross-docking approach to rank the available MMP structures for their probable successful performance in virtual screening. To determine structures that would offer best average RMSD (root mean square deviation), we performed cross-docking studies on 123 holo (protein-ligand) structures of seven MMP enzyme groups (MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, and MMP-13). RESULTS: MMP enzymes with more flexible residues had fewer structures with RMSD < 2.0 A. Further, same resolution and binding affinities, difference in ligand size, and chemotype of the co-crystalized ligand were parameters that could greatly affect the corresponding cross-dock results and the calculated average RMSD for the structures. Four of the six best MMP-12 receptors, which were identified using the average RMSD metric, had the highest EF1% (emrichment factor) in the retrospective enrichment study. CONCLUSION: According to the enrichment results, structures with lower average RMSD have a high probability of being appropriate candidates. These study findings will help in receptor selection for an MMP virtual screening protocol and lead to better enrichment of MMP inhibitors. PMID- 26872597 TI - Therapies targeting lipid peroxidation in traumatic brain injury. AB - Lipid peroxidation can be broadly defined as the process of inserting a hydroperoxy group into a lipid. Polyunsaturated fatty acids present in the phospholipids are often the targets for peroxidation. Phospholipids are indispensable for normal structure of membranes. The other important function of phospholipids stems from their role as a source of lipid mediators - oxygenated free fatty acids that are derived from lipid peroxidation. In the CNS, excessive accumulation of either oxidized phospholipids or oxygenated free fatty acids may be associated with damage occurring during acute brain injury and subsequent inflammatory responses. There is a growing body of evidence that lipid peroxidation occurs after severe traumatic brain injury in humans and correlates with the injury severity and mortality. Identification of the products and sources of lipid peroxidation and its enzymatic or non-enzymatic nature is essential for the design of mechanism-based therapies. Recent progress in mass spectrometry-based lipidomics/oxidative lipidomics offers remarkable opportunities for quantitative characterization of lipid peroxidation products, providing guidance for targeted development of specific therapeutic modalities. In this review, we critically evaluate previous attempts to use non-specific antioxidants as neuroprotectors and emphasize new approaches based on recent breakthroughs in understanding of enzymatic mechanisms of lipid peroxidation associated with specific death pathways, particularly apoptosis. We also emphasize the role of different phospholipases (calcium-dependent and independent) in hydrolysis of peroxidized phospholipids and generation of pro- and anti-inflammatory lipid mediators. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26872607 TI - Coat's like vasculopathy in leber congenital amaurosis secondary to homozygous mutations in CRB1: a case report and discussion of the management options. AB - BACKGROUND: Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, and retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features such as coat's like vasculopathy in retinitis pigmentosa patients. This is the first report of the occurrence of coat's like vasculopathy in a patient diagnosed with Leber congenital amaurosis caused by a CRB1 mutation. CASE PRESENTATION: An 18-year old Syrian female patient presented with bilateral gradual loss of vision since early childhood, with recent deterioration in her left eye. She appeared to have an asymmetric bilateral coat's like vasculopathy which was more severe in the left eye. The diagnosis of Leber congenital amaurosis was suggested, and a genetic CRB1 sequencing for the patient and her two younger siblings, who also had severe vision loss, was done, upon which the diagnosis of Leber congenital amaurosis associated with exudative retinal detachment due to coat's like vasculopathy was made. Treatment with panretinal photocoagulation was attempted in the worse left eye, but with no improvement. As the disease suddenly progressed in both eyes, pars plana vitrectomy with endolaser and silicone oil tamponade was performed in the better right eye which led to anatomical stabilization of the case without improvement in the visual acuity. CONCLUSION: Leber congenital amaurosis is reported to be associated with multiple systemic and ocular findings, none of which is coat's like vasculopathy. CRB1 gene mutations are associated with remarkable retinal findings in patients with retinitis pigmentosa and other fundus dystrophies. In this unique case we are reporting the incidence of coat's like vasculopathy in a patient diagnosed with Leber congenital amaurosis caused by CRB1 gene mutation, and its management. CRB1 mutant patients should be followed up closely as sudden progression can have permanent poor outcomes and as early management is vital in such cases. PMID- 26872608 TI - Effect of alirocumab on specific lipoprotein non-high-density lipoprotein cholesterol and subfractions as measured by the vertical auto profile method: analysis of 3 randomized trials versus placebo. AB - BACKGROUND: The effect of alirocumab on potentially atherogenic lipoprotein subfractions was assessed in a post hoc analysis using the vertical auto profile (VAP) method. METHODS: Patients from three Phase II studies with low-density lipoprotein cholesterol (LDL-C) >= 2.59 mmol/L (100 mg/dL) at baseline on stable statin therapy were randomised to receive subcutaneous alirocumab 50-150 mg every 2 weeks (Q2W) or 150-300 mg every 4 weeks (according to study) or placebo for 8 12 weeks. Samples from patients treated with alirocumab 150 mg Q2W (n = 74; dose common to all three trials) or placebo (n = 71) were analysed by VAP. Percent change in lipoprotein subfractions with alirocumab vs. placebo was analysed at Weeks 6, 8 or 12 using analysis of covariance. RESULTS: Alirocumab significantly reduced LDL-C and the cholesterol content of subfractions LDL1, LDL2 and LDL3+4. Significant reductions were also observed in triglycerides, apolipoproteins CII and CIII and the cholesterol content of very low-density, intermediate-density, and remnant lipoproteins. CONCLUSION: Alirocumab achieved reductions across a spectrum of atherogenic lipoproteins in patients receiving background statin therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01288443, NCT01288469, NCT01266876. PMID- 26872609 TI - The prognostic value of stromal and epithelial periostin expression in human breast cancer: correlation with clinical pathological features and mortality outcome. AB - BACKGROUND: PN is a secreted cell adhesion protein critical for carcinogenesis. In breast cancer, it is overexpressed compared to normal breast, and a few reports suggest that it has a potential role as a prognostic marker. METHODS: Tumour samples obtained at the time of mastectomy from 200 women followed for a median time of 18.7 years (range 0.5-29.5 years) were investigated through IHC with a polyclonal anti-PN antibody using tissue microarrays. Epithelial and stromal PN expression were scored independently according to the percentage of coloured cells; the 60th percentile of PN epithelial expression, corresponding to 1%, and the median value of PN stromal expression, corresponding to 90%, were used as arbitrary cut-offs. The relationships between epithelial and stromal PN expression and clinical-pathological features, tumour phenotype and the risk of mortality following surgery were analysed. Appropriate statistics, including the Fine and Gray competing risk proportional hazard regression model, were used. RESULTS: The expression of PN in tumour epithelial cells was significantly lower than that which was observed in stromal cells (p < 0.000). No specific association between epithelial or stromal PN expression and any of the clinical pathological parameters analysed was found as it was observed in respect to mortality when these variables were analysed individually. However, when both variables were considered as a function of the other one, the expression of PN in the stromal cells maintained a statistically significant predictive value with respect to both all causes and cancer-specific mortality only in the presence of high epithelial expression levels. No significant differences in either all causes or BCa-specific mortality rates were shown according to epithelial expression for tumours displaying higher stromal PN expression rates. However, the trends were opposite for the higher stromal values and the patients with high epithelial expression levels denoted the group with the worst prognosis, while higher epithelial values in patients with lower stromal expression levels denoted the group with the best prognosis, suggesting that PN epithelial/stromal interactions play a crucial role in breast carcinogenesis, most likely due to functional cross-talk between the two compartments. On the basis of PN expression in both compartments, we defined 4 subgroups of patients with different mortality rates with the group of patients characterized by positive epithelial and low stromal PN expression cells showing the lowest mortality risk as opposed to the groups of patients identified by a high PN expression in both cell compartments or those identified by a low or absent PN expression in both cell compartments showing the worst mortality rates. The differences were highly statistically significant and were also retained after multiparametric analysis. Competing risk analysis demonstrated that PN expression patterns characterizing each of previous groups are specifically associated with cancer-specific mortality. CONCLUSIONS: Although they require further validation through larger studies, our findings suggest that the patterns of expression of PN in both compartments can allow for the development of IHC "signatures" that maintain a strong independent predictive value of both all causes and, namely, of cancer-specific mortality. PMID- 26872610 TI - 2016 IMS Recommendations on women's midlife health and menopause hormone therapy. AB - The International Menopause Society (IMS) has produced these new 2016 recommendations on women's midlife health and menopause hormone therapy (MHT) to help guide health-care professionals in optimizing their management of women in the menopause transition and beyond. The term MHT has been used to cover therapies including estrogens, progestogens and combined regimens. For the first time, the 2016 IMS recommendations now include grades of recommendations, levels of evidence and 'good practice points', in addition to section-specific references. Where possible, the recommendations are based on and linked to the evidence that supports them, unless good-quality evidence is absent. Particular attention has been paid to published evidence from 2013 onwards, the last time the IMS recommendations were updated. Databases have been extensively searched for relevant publications using key terms specific to each specialist area within menopause physiology and medicine. Information has also been drawn from international consensus statements published by bodies such as the IMS, the European Menopause and Andropause Society and the North American Menopause Society. The recommendations have been produced by experts derived mainly from the IMS, with the assistance of key collaborators where deemed advantageous. In preparing these international recommendations, experts have taken into account geographical variations in medical care, prevalence of diseases, and country specific attitudes of the public, medical community and health authorities towards menopause management. The variation in availability and licensing of MHT and other products has also been considered. PMID- 26872611 TI - MAPK1/ERK2 as novel target genes for pain in head and neck cancer patients. AB - BACKGROUND: Genetic susceptibility plays an important role in the risk of developing pain in individuals with cancer. As a complex trait, multiple genes underlie this susceptibility. We used gene network analyses to identify novel target genes associated with pain in patients newly diagnosed with squamous cell carcinoma of the head and neck (HNSCC). RESULTS: We first identified 36 cancer pain-related genes (i.e., focus genes) from 36 publications based on a literature search. The Ingenuity Pathway Analysis (IPA) analysis identified additional genes that are functionally related to the 36 focus genes through pathway relationships yielding a total of 82 genes. Subsequently, 800 SNPs within the 82 IPA-selected genes on the Illumina HumanOmniExpress-12v1 platform were selected from a large scale genotyping effort. Association analyses between the 800 candidate SNPs (covering 82 genes) and pain in a patient cohort of 1368 patients with HNSCC (206 patients with severe pain vs. 1162 with non-severe pain) showed the highest significance for MAPK1/ERK2, a gene belonging to the MAP kinase family (rs8136867, p value = 8.92 * 10(-4); odds ratio [OR] = 1.33, 95 % confidence interval [CI]: 1.13-1.58). Other top genes were PIK3C2G (a member of PI3K [complex], rs10770367, p value = 1.10 * 10(-3); OR = 1.46, 95 % CI: 1.16-1.82), TCRA (the alpha chain of T-cell receptor, rs6572493, p value = 2.84 * 10(-3); OR = 0.70, 95 % CI: 0.55-0.88), PDGFC (platelet-derived growth factor C, rs6845322, p value = 4.88 * 10(-3); OR = 1.32, 95 % CI: 1.09-1.60), and CD247 (a member of CD3, rs2995082, p value = 7.79 * 10(-3); OR = 0.76, 95 % CI: 0.62-0.93). CONCLUSIONS: Our findings provide novel candidate genes and biological pathways underlying pain in cancer patients. Further study of the variations of these candidate genes could inform clinical decision making when treating cancer pain. PMID- 26872612 TI - Excess iodide downregulates Na(+)/I(-) symporter gene transcription through activation of PI3K/Akt pathway. AB - Transcriptional mechanisms associated with iodide-induced downregulation of NIS expression remain uncertain. Here, we further analyzed the transcriptional regulation of NIS gene expression by excess iodide using PCCl3 cells. NIS promoter activity was reduced in cells treated for 12-24 h with 10(-5) to 10(-3) M NaI. Site-directed mutagenesis of Pax8 and NF-kappaB cis-acting elements abrogated the iodide-induced NIS transcription repression. Indeed, excess iodide (10(-3) M) excluded Pax8 from the nucleus, decreased p65 total expression and reduced their transcriptional activity. Importantly, p65-Pax8 physical interaction and binding to NIS upstream enhancer were reduced upon iodide treatment. PI3K/Akt pathway activation by iodide-induced ROS production is involved in the transcriptional repression of NIS expression. In conclusion, the results indicated that excess iodide transcriptionally represses NIS gene expression through the impairment of Pax8 and p65 transcriptional activity. Furthermore, the data presented herein described novel roles for PI3K/Akt signaling pathway and oxidative status in the thyroid autoregulatory phenomenon. PMID- 26872613 TI - Expression of Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) in somatotropinomas: Relationship with Aryl hydrocarbon receptor Interacting Protein (AIP) and in vitro effects of fenofibrate in GH3 cells. AB - PURPOSE: To search for a possible role of Peroxisome Proliferator-Activated Receptor alpha (PPARalpha), a molecular partner of the Aryl hydrocarbon receptor Interacting Protein (AIP), in somatotropinomas. METHODS: Tumours from 51 acromegalic patients were characterized for PPARalpha and AIP expression by immunohistochemistry (IHC) and/or Real Time RT-PCR. Data were analysed according to tumour characteristics and pre-operative treatment with somatostatin analogues (SSA). The effects of fenofibrate were studied in GH3 cells in vitro. RESULTS: PPARalpha was expressed in most somatotropinomas. A modest relationship was found between PPARalpha and AIP expression, both being significantly higher in the presence of pre-operative SSA. However, only AIP expression was influenced by the response to treatment. Dual effects of fenofibrate were observed in GH3 cells, consisting of cell growth inhibition and an increase in GH secretion inhibited by octreotide. CONCLUSIONS: PPARalpha is a new player in somatotropinomas. Potential interactions between PPARalpha agonists and SSA may deserve further investigation. PMID- 26872614 TI - 17beta-Estradiol alters oxidative damage and oxidative stress response protein expression in the mouse mammary gland. AB - Although substantial evidence has demonstrated that parity and 17beta-estradiol (E2) reduce mammary carcinogenesis, it is not clear how this protection is conferred. Thus, we examined the effects of parity and E2 treatment in the mammary glands of ovariectomized 15 week-old virgin mice, 15 week-old primiparous mice, and 9 month-old retired breeders. E2 treatment significantly increased lipid peroxidation, protein carbonylation, and protein nitrosylation in the virgin mice, but not in the age-matched primiparous mice or retired breeders. Mammary gland expression of the oxidative stress response protein Cu/Zn superoxide dismutase was consistently reduced in all of the E2-treated mice regardless of parity. Expression of the oxidative stress and DNA repair protein apurinic endonuclease (Ape1) was significantly increased only in the mammary glands of the E2-treated retired breeders. These findings suggest that E2 and parity help to reduce mammary oncogenesis by maintaining the structure and function of proteins, lipids, and DNA. PMID- 26872615 TI - MiR-23b targets cyclin G1 and suppresses ovarian cancer tumorigenesis and progression. AB - BACKGROUND: It has been proposed that cyclin G1 (CCNG1) participates in p53 dependent G1-S and G2 checkpoints and might function as an oncogenic protein in the initiation and metastasis of ovarian carcinoma. MicroRNA 23b (miR-23b) is a critical regulatory factor in the progression of many cancer cell types that targets the relevant genes. METHODS: MiR-23b expression in ovarian tissues was quantified by quantitative reverse transcription-PCR. The ovarian cancer cell lines OVCAR3, HO8910-PM, and SKOV3/DDP were transfected with miR-23b, after we assayed the cell phenotype and expression of the relevant molecules. Dual luciferase reporter assay and a xenograft mouse model were used to examine the expression of miR-23b and its target gene CCNG1. RESULTS: MIR23B mRNA expression was significantly lower in epithelial ovarian carcinoma and borderline tumors than in normal ovarian tissues and benign tumors, and miR-23b expression among ages and pathological subtypes was significantly different. CCNG1 mRNA expression was significantly lower in normal ovarian tissues than in benign tumors, borderline tumors, and ovarian carcinomas, and expression among pathological subtypes was significantly different. MiR-23b overexpression inhibited ovarian cancer cell proliferation, invasion, and migration, and induced apoptosis. Dual luciferase reporter assay showed that miR-23b bound with the 3' untranslated region of CCNG1. MiR-23b overexpression significantly downregulated CCNG1, urokinase, survivin, Bcl-xL, P70S6K, and matrix metallopeptidase-9 (MMP9) mRNA and protein expression. Furthermore, miR-23b inhibited tumor growth and suppressed CCNG1 expression in vitro. CONCLUSIONS: Our findings show that miR-23b may inhibit ovarian cancer tumorigenesis and progression by downregulating CCNG1 and the expression of the relevant genes. MiR-23b is a potentially novel application for regulating ovarian carcinoma progression. PMID- 26872616 TI - Results of a prospective multicenter neuroendocrine tumor registry reporting on clinicopathologic characteristics of Greek patients. AB - BACKGROUND: The rare incidence of neuroendocrine neoplasms (NENs) has contributed to a paucity of large epidemiologic studies of patients with this condition. We investigated the occurrence and clinicopathologic features of NENs in Greece. METHODS: Between October 2010 and November 2012 we collected data on 246 newly diagnosed patients from a broad-based multi-institutional registry that comprises eight academic and hospital sites in Greece. The WHO 2010 pathologic classification and the 7th AJCC Staging system was applied in all cases. RESULTS: Of all patients 94 % had a sporadic and 6 % a multiple endocrine neoplasia tumor; 63.4 % were gastroenteropancreatic-(GEP)-NENs, 17.9 % Head & Neck NENs, 9.8 % NENs of Unknown Primary, 6.5 % Lung NENs and 2.4 % Pheochromocytomas. Gastric and pancreatic NENs were the most common primary sites. Poorly differentiated neuroendocrine carcinomas (NEC) were 9.3 %, all sporadic. Fifteen percent of patients were asymptomatic at presentation, 24 % had a first symptom of the disease related to endocrine syndrome and 61 % had symptoms related to locally advanced or metastatic disease. Metastatic disease was established in 25 % of tumors most frequently in the GEP NEN group. Findings are presented according to Ki-67 distribution. MRI had a higher diagnostic positive yield than Octreoscan. Somatostatin analogs, lanreotide and octreotide acetate, were prescribed at 38.5 & 61.5 % of NEN patients respectively and were found to be equally effective at providing symptomatic relief. CONCLUSIONS: This is to our knowledge the first study of a Greek tumor registry and one of the few European Registries providing information regarding clinicopathologic characteristics and therapies in patients with neuroendocrine tumors of various origin sites, beyond GEP NENs. PMID- 26872617 TI - Role of mass spectrometry in steroid assays. AB - In addition to protein hormones, steroids measurement constitutes the basis of modern endocrinology. Immunoassays have shown their limits in this field. In contrast, mass spectrometry shows an excellent sensitivity and specificity that make it the method of choice for steroids assays. The recent introduction of UHPLC-MS is a major advance which reinforces this position. In fact, mass spectrometry provides a lot of advantages such as determination of certain steroids in saliva, diagnosis of enzyme deficiencies, or measurement of molecules previously inaccessible like aldosterone. However, standardization is still needed to ensure good comparability of results between laboratories. In the future, mass spectrometry should not replace the immunoassays but rather complement it. PMID- 26872619 TI - New insight into the shortening of the collagen fibril D-period in human cornea. AB - Collagen fibrils type I display a typical banding pattern, so-called D periodicity, of about 67 nm, when visualized by atomic force or electron microscopy imaging. Herein we report on a significant shortening of the D-period for human corneal collagen fibrils type I (21 +/- 4 nm) upon air-drying, whereas no changes in the D-period were observed for human scleral collagen fibrils type I (64 +/- 4 nm) measured under the same experimental conditions as the cornea. It was also found that for the corneal stroma fixed with glutaraldehyde and air dried, the collagen fibrils show the commonly accepted D-period of 61 +/- 8 nm. We used the atomic force microscopy method to image collagen fibrils type I present in the middle layers of human cornea and sclera. The water content in the cornea and sclera samples was varying in the range of .066-.085. Calculations of the D-period using the theoretical model of the fibril and the FFT approach allowed to reveal the possible molecular mechanism of the D-period shortening in the corneal collagen fibrils upon drying. It was found that both the decrease in the shift and the simultaneous reduction in the distance between tropocollagen molecules can be responsible for the experimentally observed effect. We also hypothesize that collagen type V, which co-assembles with collagen type I into heterotypic fibrils in cornea, could be involved in the observed shortening of the corneal D-period. PMID- 26872618 TI - Prevention of Necrotizing Enterocolitis Through Manipulation of the Intestinal Microbiota of the Premature Infant. AB - PURPOSE: In spite of four decades of research, necrotizing enterocolitis (NEC) remains the most common gastrointestinal complication in premature infants with high mortality and long-term morbidity. The composition of the intestinal microbiota of the premature infant differs dramatically from that of the healthy term infant and appears to be an important risk factor for NEC. METHODS: We review the evidence of an association between intestinal dysbiosis and NEC and summarize published English language clinical trials and cohort studies involving attempts to manipulate the intestinal microbiota in premature infants. FINDINGS: Promising NEC prevention strategies that alter the intestinal microbiota include probiotics, prebiotics, synbiotics, lacteroferrin, and human milk feeding. IMPLICATIONS: Shaping the intestinal microbiota of the premature infant through human milk feeding and dietary supplements decreases the risk of NEC. Further studies to identify the ideal microbial composition and the most effective combination of supplements are indicated. PMID- 26872620 TI - Genetics of glucocorticoid regulation and posttraumatic stress disorder--What do we know? AB - CASTRO-VALE, I., E.F.C. van Rossum, J.C. Machado, R. Mota-Cardoso and D. Carvalho. Genetics of glucocorticoid regulation and posttraumatic stress disorder What do we know? NEUROSCI. BIOBEHAV. REV. 43 (1) XXX-XXX, 2014 - Posttraumatic stress disorder (PTSD) develops in a small proportion of those who have been exposed to a traumatic event. Genetic factors are estimated to be responsible for 30% of the variance in PTSD risk. Dysfunction of the hypothalamic-pituitary adrenal (HPA)-axis in PTSD has been found, particularly hypersensitivity of the glucocorticoid receptor (GR). In this review we aim to understand the genetic factors that influence glucocorticoid function in PTSD. Glucocorticoid action is regulated by a corticotrophin-releasing hormone, arginine vasopressin (AVP)/oxytocin pathway, GR, and regulators such as co-chaperone FKBP5. Single nucleotide polymorphisms (SNPs) in the GR gene, CRHR1 gene and FKBP5 gene affect HPA-axis sensitivity. The GR gene SNP BclI has been associated with hypersensitivity to glucocorticoids and PTSD symptoms. FKBP5 gene SNPs interacted with childhood adversity to moderate PTSD risk and in particular, the rs9470080 SNP was independently associated with lifetime PTSD. SNPs in the CRHR1 gene were also associated with PTSD risk. Gene-environment interaction studies have highlighted the importance of multifactorial vulnerability in PTSD, with epigenetic mechanisms contributing to the equation. PMID- 26872621 TI - Two cases of autoimmune and secondary pulmonary alveolar proteinosis during immunosuppressive therapy in dermatomyositis with interstitial lung disease. AB - Interstitial lung disease (ILD) with dermatomyositis often requires intensive immunosuppressive therapy. Here, we report two cases of pulmonary alveolar proteinosis (PAP) in dermatomyositis with ILD. One case was secondary PAP, and the other was autoimmune PAP positive for the anti-granulocyte macrophage-colony stimulating factor antibody. PAP arose during immunosuppressive therapy and symptoms ceased by attenuating immunosuppression. Exacerbation of pulmonary lesions during intensive immunosuppressive therapy may distinguish PAP from worsening ILD and attenuating immunosuppression should be considered. PMID- 26872622 TI - Effects of radiation from a radiofrequency identification (RFID) microchip on human cancer cells. AB - PURPOSE: Radiofrequency identification (RFID) microchips are used to remotely identify objects, e.g. an animal in which a chip is implanted. A passive RFID microchip absorbs energy from an external source and emits a radiofrequency identification signal which is then decoded by a detector. In the present study, we investigated the effect of the radiofrequency energy emitted by a RFID microchip on human cancer cells. MATERIALS AND METHODS: Molt-4 leukemia, BT474 breast cancer, and HepG2 hepatic cancer cells were exposed in vitro to RFID microchip-emitted radiofrequency field for 1 h. Cells were counted before and after exposure. Effects of pretreatment with the spin-trap compound N-tert-butyl alpha-phenylnitrone or the iron-chelator deferoxamine were also investigated. Results We found that the energy effectively killed/retarded the growth of the three different types of cancer cells, and the effect was blocked by the spin trap compound or the iron-chelator, whereas an inactive microchip and energy from the external source had no significant effect on the cells. Conclusions Data of the present study suggest that radiofrequency field from the microchip affects cancer cells via the Fenton Reaction. Implantation of RFID microchips in tumors may provide a new method for cancer treatment. PMID- 26872623 TI - Trigeminal nerve stimulation (TNS) for social anxiety disorder: A case study. PMID- 26872624 TI - Augmented simvastatin cytotoxicity using optimized lipid nanocapsules: a potential for breast cancer treatment. AB - CONTEXT: We noticed paucity in exploiting solutol-based lipid nanocapsules in statins formulations though they carry all favorable properties that are needed for cancer passive targeting such as their small particle size, stealth properties, ability to highly accommodate lipophilic drugs, good internalization and P-gp pump inhibition. OBJECTIVE: The aim of this study was to design and optimize new simvastatin drug delivery systems; lipid nanocapsules intended for administration through the intravenous route as potential treatment for breast cancer. METHODS: Optimized nanocapsules were prepared by the phase-inversion method according to a D-optimal mixture design, characterized and assessed for their cytotoxicity. RESULTS: Three successful models for particle size, polydispersity index (PDI) and percentage of drug released after 48 h were generated. The prepared lipid nanocapsules acquired spherical and homogenous morphology, good stability and tolerance to sterilization. The obtained release profiles demonstrated desired sustained release pattern. Furthermore, testing selected formulations on human breast cancer adenocarcinoma cells showed augmented cytotoxicity of simvastatin reaching low IC50 values as 1.4 +/- 0.02 MUg/ml compared to the pure drug. CONCLUSION: The proposed lipid nanocapsules pose promising candidates as simvastatin carriers intended for the targeting of breast cancer. PMID- 26872625 TI - Expression analysis of cytosolic DNA-sensing pathway genes in the intestinal mucosal layer of necrotic enteritis-induced chicken. AB - Necrotic enteritis (NE) is a serious problem to the poultry farms, which report NE outbreaks more than once per year, as a result of the inappropriate use of antibiotics in the feed. The NE affected bird die rapidly as a result of various pathophysiological complications in the intestine and immune system. Also, several studies have reported that the genes exclusively related to intestine and immune functions are significantly altered in response to NE. In this study, NE was induced in two genetically disparate chicken lines that are resistant (line 6.3) and sensitive (line 7.2) to avian leukosis and Marek's disease. The intestinal mucosal layer was collected from NE-induced and control chickens, and subjected to RNA-sequencing analysis. The involvement of differentially expressed genes in the intestinal mucosal layer of line 6.3 and 7.2 with the immune system related pathways was investigated. Among the identified immune system-related pathways, a candidate pathway known as chicken cytosolic DNA-sensing pathway (CDS pathway) was selected for further investigation. RNA-sequencing and pathway analysis identified a total of 21 genes that were involved in CDS pathway and differentially expressed in the intestinal mucosal layer of lines 6.3 and 7.2. The expression of CDS pathway genes was further confirmed by real-time qPCR. In the results, a majority of the CDS pathway genes were significantly altered in the NE-induced intestinal mucosal layer from lines 6.3 and 7.2. In conclusion, our study indicate that NE seriously affects several genes involved in innate immune defense and foreign DNA sensing mechanisms in the chicken intestinal mucosal layer. Identifying the immune genes affected by NE could be an important evidence for the protective immune response to NE-causative pathogens. PMID- 26872626 TI - Development of porcine ficolin-alpha monoclonal and polyclonal antibodies for determining the binding capacity of multiple GlcNAc-binding proteins to bacterial danger components. AB - Ficolins are a group of oligomeric defense proteins assembled from collagen-like stalks and fibrinogen-like domains that have common biochemical specificity for N acetyl-d-glucose amine (GlcNAc) and can function as opsonins. In this report, GlcNAc-binding protein (GBP) purified from porcine nonimmune serum was biochemically characterized as ficolin-alpha. Ficolin-alpha was used as an immunogen to generate both rabbit polyclonal and murine monoclonal anti-ficolin alpha antibodies, which are not yet commercially available. GBPs have been shown to be present in many animals, including humans; however, their functions are largely unknown. GBPs from chicken, dog, horse, bovine, and human sera were isolated using various chromatography methods. Interestingly, anti-ficolin-alpha antibody showed cross-reaction with those animal sera GBPs. Furthermore, anti ficolin-alpha antibody was reactive with the GlcNAc eluate of Escherichia coli O26-bound and Salmonella-bound porcine serum proteins. Functionally, GBPs and bacteria-reactive pig serum proteins were able to bind with pathogen-associated molecular patterns such as lipopolysaccharides and lipoteichoic acids. Our studies demonstrate that ficolin-alpha specific antibody was reactive with GBPs from many species as well as bacteria-reactive serum proteins. These proteins may play important roles in innate immunity by sensing danger components that can lead to antibacterial activity. PMID- 26872627 TI - Identification of stable reference genes for quantitative PCR in cells derived from chicken lymphoid organs. AB - Quantitative polymerase chain reaction (qPCR) is a powerful technique for quantification of gene expression, especially genes involved in immune responses. Although qPCR is a very efficient and sensitive tool, variations in the enzymatic efficiency, quality of RNA and the presence of inhibitors can lead to errors. Therefore, qPCR needs to be normalised to obtain reliable results and allow comparison. The most common approach is to use reference genes as internal controls in qPCR analyses. In this study, expression of seven genes, including beta-actin (ACTB), beta-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-glucuronidase (GUSB), TATA box binding protein (TBP), alpha-tubulin (TUBAT) and 28S ribosomal RNA (r28S), was determined in cells isolated from chicken lymphoid tissues and stimulated with three different mitogens. The stability of the genes was measured using geNorm, NormFinder and BestKeeper software. The results from both geNorm and NormFinder were that the three most stably expressed genes in this panel were TBP, GAPDH and r28S. BestKeeper did not generate clear answers because of the highly heterogeneous sample set. Based on these data we will include TBP in future qPCR normalisation. The study shows the importance of appropriate reference gene normalisation in other tissues before qPCR analysis. PMID- 26872628 TI - Protective efficacy of Streptococcus iniae derived enolase against Streptococcal infection in a zebrafish model. AB - Enolase (ENO) is one of the surface-exposed proteins of Streptococcus iniae, which previously had been identified as a plasminogen-binding protein. In this study, ENO was evaluated to induce cross-protective immunity against S. iniae and Streptococcus parauberis which are major pathogens causing streptococcosis in fish. Immunoblot analysis shows that S. iniae recombinant ENO (rENO) produced in Escherichia coli was cross-reactive with antisera against S. iniae, and S. parauberis serotype I and II. In the challenge experiment of streptococcal infection after vaccination in zebrafish, rENO elicited a similar protection with a whole cell bacterin against S. iniae and S. parauberis, which suggests its feasibility as an efficient vaccine against streptococcosis. PMID- 26872629 TI - Removal of Retained Adherent Placental Remnants Using the Hysteroscopy Endo Operative System. AB - STUDY OBJECTIVE: Removal of retained adherent placental remnants (RAPRs) may be challenging using traditional 5Fr or 7Fr hysteroscopic grasping forceps because they are very small. This is particularly true when the retained placental remnant is large. This video demonstrates the advantages of using the Hysteroscopy Endo-Operative System (HEOS), a specially designed operative hysteroscope with a 13Fr working channel, to remove retained placental remnants. DESIGN: Step-by-step explanation of the technique using videos and pictures (educative video) (Canadian Task Force Classification III). SETTING: Third Xiangya Hospital of Central South University, Hunan, China. PATIENT: A 32-year old woman was diagnosed with RAPRs 5 weeks after the evacuation of retained placenta after a spontaneous abortion at 16 weeks' gestation. Gynecologic examination revealed an anterior 8-week uterus and no tenderness. Serum beta human chorionic gonadotropin was 150 mIU/L. Sonography revealed an irregular intrauterine mass, 3.5 cm * 3.5 cm * 3 cm in size. INTERVENTION: Removal of RAPRs using HEOS (Sopro-comeg Company, Bordeaux, France). MEASUREMENT AND MAIN RESULTS: The operation time was only 12 minutes. The RAPRs were removed completely and quickly in 1 procedure with no complications. The serum beta-human chorionic gonadotropin titer normalized 1 week after the procedure. This study was approved by the institutional review board of the Third Xiangya Hospital of Central South University. CONCLUSIONS: When indicated, removal of RAPRs using HEOS is safe and simple because of its large and strong cold forceps. Additionally, it avoids electrical and thermal injury to the endometrium, which is particularly important in a population that wants to preserve fertility. PMID- 26872630 TI - Laparoscopic Management of Ovarian Cancer Patients With Localized Carcinomatosis and Lymph Node Metastases: Results of a Retrospective Multi-institutional Series. AB - STUDY OBJECTIVE: To investigate the feasibility and safety of laparoscopic cytoreduction in ovarian cancer patients with localized carcinomatosis or lymph node involvement. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: Multi-institutional study performed in 6 referral gynecologic oncology units. PATIENTS: Between June 2005 and December 2014, preoperatively presumed early-stage ovarian cancer patients, who accidentally revealed localized carcinomatosis or lymph node involvement at laparoscopic evaluation or at postoperative pathological examination managed by the laparoscopic approach. INTERVENTIONS: All patients with limited carcinomatosis and/or lymph node metastases underwent complete laparoscopic cytoreduction. MEASUREMENTS AND RESULTS: Sixty-nine patients were included in the analysis. Twenty-eight (40.6%) patients were staged III C because they had lymph node metastases. Pelvic lymphadenectomy was performed in 75.4% of cases, whereas aortic lymphadenectomy was performed in 79.7% of cases. Lymph node metastases were found in pelvic and aortic regions in 11 and 13 patients, respectively, whereas 4 patients had lymph node metastases in both regions. Twelve (17.4%) patients underwent complete pelvic peritonectomy because of the presence of nodules localized in several pelvic region sites. As of May 2015, the median follow-up was 35 months, and the median disease-free survival was 29 months. The 2-year disease-free survival rate was 77.1%, whereas the 2-year overall survival rate was 90.6%. The median time to recurrence was 26 months (range, 6 -55 months); 15 (21.7%) patients developed recurrence. CONCLUSION: The present study shows the technical and clinical feasibility of laparoscopic cytoreduction in ovarian cancer patients with limited carcinomatosis or lymph node involvement. PMID- 26872631 TI - Enhancing T cell therapy by overcoming the immunosuppressive tumor microenvironment. AB - Immune response to tumors can be successfully oriented for therapeutic purposes, as shown by the clinical efficacy of checkpoint blockade in extending the survival of patients with certain solid and hematologic neoplasms. Nonetheless, numerous patients do not benefit from these new treatments. Tumor-specific CD8(+) T lymphocytes, either endogenously revived by checkpoint interference or adoptively transferred after in vitro expansion and retargeting, can be extremely efficient in controlling metastatic disease but have to overcome a number of restraints imposed by growing tumors. This immune escape relies on a profound modification of the tumor environment, which is rendered less permissive to lymphocyte arrival, persistence, and functional activity. We review here emerging findings on the main negative circuits limiting the efficacy of cancer immunotherapy, as well as novel and conventional approaches that can translate into rational combination therapies. PMID- 26872632 TI - Uber for healthcare. PMID- 26872633 TI - Alpha-7 nicotinic agonist improves cognition in schizophrenia. PMID- 26872634 TI - EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): genetic profile and clinical implications. AB - The EBF1-PDGFRB gene fusion accounts for <1% of B-cell precursor acute lymphoblastic leukemia (ALL) cases and occurs within the Philadelphia-like ALL subtype. We report 15 EBF1-PDGFRB-positive patients from childhood ALL treatment trials (ALL 97/99, UKALL 2003, UKALL 2011) in the United Kingdom. The fusion arose from interstitial deletion of 5q33 (n = 11), balanced rearrangement (n = 2), or complex rearrangement (n = 2). There was a predominance of females (n = 11), median age of 12 years, and median white blood cell count of 48.8 * 10(9)/L. Among 12 patients who achieved complete remission on earlier trials (ALL 97/99 and UKALL 2003), 10 were positive for minimal residual disease (MRD) at the end of induction, and 7 relapsed 18 to 59 months after diagnosis. The majority (9 of 12) remained alive 6 to 9 years after diagnosis. There are reports of EBF1-PDGFRB positive patients who are refractory to conventional chemotherapy who achieve complete response when treated with the tyrosine kinase inhibitor imatinib. These findings have prompted screening for EBF1-PDGFRB in patients entered onto the current UKALL 2011 trial for whom induction therapy failed, who did not achieve remission by day 29, or who remained MRD positive (>0.5%) at week 14. Two UKALL 2011 patients, positive for EBF1-PDGFRB, received imatinib; 1 died 6 months after a matched unrelated bone marrow transplant as a result of undefined encephalopathy, and the other remained in remission 10 months after diagnosis. PMID- 26872635 TI - Double loop reconstruction following pancreaticoduodenectomy for malignant tumor: Short-term outcome. AB - BACKGROUND: To evaluate the use of a double loop reconstruction following pylorus preserving proximal pancreaticoduodenectomy (PPPPD). METHODS: Morbidity and mortality were evaluated in 55 patients undergoing PPPPD for malignant tumors, followed by a double loop reconstruction. RESULTS: The mean intra-operative blood loss was 908mL+/-531. In-hospital mortality was 5.4% (3/55 pts). The mean length of hospital stay was 17+/-5 days (range 12-45 days). Postoperative complications occurred in 25 patients (46.2%). Five patients developed an anastomotic leak, one biliary and four pancreatic (4/55; 7%). Delayed gastric emptying occurred in 8 patients (14.5%). Reoperation was required in two patients for hemorrhage. CONCLUSIONS: A double loop alimentary reconstruction following PPPPD led to a low incidence of DGE and pancreatic fistula. Although mortality rate was higher than that reported by referral centres, this technique has been performed in a not specialized unit attaining acceptable results. PMID- 26872636 TI - Psychometric validation of a patient-reported measure of physical functioning in sporadic inclusion body myositis. AB - INTRODUCTION: To assess self-reported physical functioning in patients with sporadic inclusion body myositis (sIBM), the sIBM Physical Functioning Assessment (sIFA) was developed. This research establishes the validity, reliability, and responsiveness of the sIFA in patients with sIBM. METHODS: Data from 3 small, noninterventional, observational studies were analyzed. Several measures of physical function were included to assess validity. Reliability (Cronbach alpha, test-retest intraclass correlations), construct validity (correlations, analyses of variance), and responsiveness (effect size estimates) were evaluated. RESULTS: Cronbach alphas (range = 0.86-0.91) and test-retest reliability (0.91) were highly satisfactory. Correlations with other measures provided evidence of convergent validity. sIBM patients able to walk without assistive devices scored significantly better on the sIFA (means = 36.0-47.05) than those who required power mobility or wheelchairs (means = 54.9-71.5), demonstrating the discriminating ability of the sIFA. Effect size estimates of responsiveness suggested mild functional progression. CONCLUSIONS: Psychometric analyses of the sIFA demonstrate satisfactory reliability, validity, and responsiveness. Muscle Nerve 54: 658-665, 2016. PMID- 26872637 TI - The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children. AB - OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters. METHODS: Tumour tissue from classical HL (cHL) (n = 87) and nodular lymphocyte predominant HL (NLPHL) (n = 11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages. RESULTS: In cHL, EBV positivity was more common in low age (P < 0.001) and in mixed cellularity (MC) (P < 0.001). Higher mast cell infiltration was seen in stage III-IV (P < 0.001), and with presence of B-symptoms (P = 0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (P = 0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells. CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters. PMID- 26872638 TI - Prevalence and Molecular Genotyping of Noroviruses in Market Oysters, Mussels, and Cockles in Bangkok, Thailand. AB - Noroviruses are the most common cause of acute gastroenteritis associated with bivalve shellfish consumption. This study aimed to detect and characterize noroviruses in three bivalve shellfish species: oysters (Saccostrea forskali), cockles (Anadara nodifera), and mussels (Perna viridis). The virus concentration procedure (adsorption-twice elution-extraction) and a molecular method were employed to identify noroviruses in shellfish. RT-nested PCR was able to detect known norovirus GII.4 of 8.8 * 10(-2) genome copies/g of digestive tissues from oyster and cockle concentrates, whereas in mussel concentrates, the positive result was seen at 8.8 * 10(2) copies/g of digestive tissues. From August 2011 to July 2012, a total of 300 shellfish samples, including each of 100 samples from oysters, cockles, and mussels were collected and tested for noroviruses. Norovirus RNA was detected in 12.3 % of shellfish samples. Of the noroviruses, 7.7 % were of the genogroup (G) I, 2.6 % GII, and 2.0 % were mixed GI and GII. The detection rate of norovirus GI was 2.1 times higher than GII. With regards to the different shellfish species, 17 % of the oyster samples were positive, while 14.0 and 6.0 % were positive for noroviruses found in mussels and cockles, respectively. Norovirus contamination in the shellfish occurred throughout the year with the highest peak in September. Seventeen norovirus-positive PCR products were characterized upon a partial sequence analysis of the capsid gene. Based on phylogenetic analysis, five different genotypes of norovirus GI (GI.2, GI.3, GI.4, GI.5, and GI.9) and four different genotypes of GII (GII.1, GII.2, GII.3, and GII.4) were identified. These findings indicate the prevalence and distribution of noroviruses in three shellfish species. The high prevalence of noroviruses in oysters contributes to the optimization of monitoring plans to improve the preventive strategies of acute gastroenteritis. PMID- 26872639 TI - End of Year 2015 in Polio Endemic Pakistan: Yet Another Beginning Towards End. PMID- 26872640 TI - Food Hardship and Obesity in a Sample of Low-Income Immigrants. AB - Very little work has examined the relationship between food hardship (having inconsistent financial resources to buy food) and obesity among immigrant groups. A cross-sectional study was conducted in a low-income, multi-racial/ethnic adult sample in greater Boston, MA (n = 828). Modified Poisson regression models estimated the association between food hardship obesity (BMI >= 30) among adults reporting food hardship; interactions were tested by place of birth. Body mass index (BMI) was based on anthropometric height and weight. In adjusted models, those experiencing food hardship were more likely to be obese (RR 1.17, CI 1.07, 1.29) than those not experiencing food hardship. Participants from Haiti reporting food hardship were more likely to be obese than those not reporting hardship (RR 1.58, CI 1.23, 2.04); this was not the case among other groups (US born, Puerto Rican, Latin American, Other). The relationship between food hardship and weight may vary among immigrant subgroups. PMID- 26872641 TI - Social Environmental Influences on Smoking and Cessation: Qualitative Perspectives Among Chinese-Speaking Smokers and Nonsmokers in California. AB - This qualitative study examines the social environmental influences on smoking and cessation from the perspectives of Chinese smokers and household nonsmokers in California. Seven focus groups were conducted with 63 participants. Three culturally influenced levels of potential intervention emerged from constant comparative analysis. At the individual level, participants focused more on irritating odor than health harms of exposure and had inaccurate beliefs about harms of smoking and cessation. At the relational level, peers kept smokers connected to pro-smoking norms. There was conflict in the home about smoking and failed cessation, but smokers recognized the benefits of cessation for family harmony and children's health. Physicians encouraged cessation but this tended to be insufficient to prompt action unless a smoker felt ill. At the societal level, participants recognized changes in social acceptability and environmental regulation of smoking upon immigration. Better implementation of smokefree policies, plus culturally nuanced strategies for equipping both nonsmokers and smokers to become smokefree, are needed. PMID- 26872642 TI - The Effect of Language on the Discharge Process in a Pediatric Emergency Department. AB - Health disparities linked to language have been clearly described in the literature. However, little is known about potential disparities in care related to language in the Pediatric Emergency Department (PED). This was a cross sectional observational study using convenience sampling of English and Spanish PED discharges before and after electronic medical record (EMR) implementation. There were minimal differences between English and Spanish-speaking families in interactional elements and basic dialogue during discharge. Yet Spanish-speaking families had longer wait times to discharge once the decision to discharge was made. Interestingly, implementation of EMR added efficiency in terms of seeing a physician after arrival and equalizing the discharge instruction process between both groups. Contrary to literature on language-related health disparities, our study revealed minimal differences between English and Spanish-speaking families specifically in the PED discharge process. PMID- 26872643 TI - The promise of urethral pressure reflectometry: an update. AB - INTRODUCTION AND HYPOTHESIS: The urethral closure mechanism in women is incompletely understood. Measuring closure function in a collapsed urethral tube without distending the tube and changing its natural shape is impossible with conventional methods. Over the last decade, studies with urethral pressure reflectometry (UPR), a method that measures pressure and the corresponding cross sectional area along the entire length of the urethra continuously by means of acoustic reflectometry, have been performed. The studies have mainly been performed on patients with stress urinary incontinence (SUI). METHODS: Our aim was to provide an overview of the studies conducted with UPR, establishing whether the method may be used in clinical practice. We reviewed all literature published on UPR. RESULTS: Urethral pressure reflectometry is easily performed with limited bother for the patient. The catheter consists of a 45-cm-long PVC tube connected to a thin and highly flexible polyurethane bag, which is placed in the urethra. When inserted, the bag only occupies 0.4 mm(2) of the urethra, respecting the natural shape and orientation of the urethra and, most importantly; respecting the laws of physics when measuring urethral pressure. UPR can discriminate patients with SUI from continent women and separate assessment of the sphincter function and support system is possible. Also, UPR has revealed statistically significant differences in urethral pressures after drug therapy for SUI. CONCLUSIONS: We conclude that UPR has a place in clinical practice. The method has shown groundbreaking potential in the understanding of urethral dysfunction in SUI patients. PMID- 26872644 TI - Impact of parity on ewe vaginal mechanical properties relative to the nonhuman primate and rodent. AB - INTRODUCTION AND HYPOTHESIS: Parity is the leading risk factor for the development of pelvic organ prolapse. To assess the impact of pregnancy and delivery on vaginal tissue, researchers commonly use nonhuman primate (NHP) and rodent models. The purpose of this study was to evaluate the ewe as an alternative model by investigating the impact of parity on the ewe vaginal mechanical properties and collagen structure. METHODS: Mechanical properties of 15 nulliparous and parous ewe vaginas were determined via uniaxial tensile tests. Collagen content was determined by hydroxyproline assay and collagen fiber thickness was analyzed using picrosirius red staining. Outcome measures were compared using Independent samples t or Mann-Whitney U tests. ANOVA (Gabriel's pairwise post-hoc test) or the Welch Alternative for the F-ratio (Games Howell post-hoc test) was used to compare data with previously published NHP and rodent data. RESULTS: Vaginal tissue from the nulliparous ewe had a higher tangent modulus and tensile strength compared with the parous ewe (p < 0.025). The parous ewe vagina elongated 42 % more than the nulliparous ewe vagina (p = 0.015). No significant differences were observed in collagen structure among ewe vaginas. The tangent modulus of the nulliparous ewe vagina was not different from that of the NHP or rodent (p = 0.290). Additionally, the tangent moduli of the parous ewe and NHP vaginas did not differ (p = 0.773). CONCLUSIONS: Parity has a negative impact on the mechanical properties of the ewe vagina, as also observed in the NHP. The ewe may serve as an alternative model for studying parity and ultimately prolapse development. PMID- 26872645 TI - Carl Gustav Nilsson 1944-2015. PMID- 26872646 TI - Prevalence of pelvic floor disorders in women with suspected gynecological malignancy: a survey-based study. AB - INTRODUCTION AND HYPOTHESIS: Understanding of pelvic floor disorders among women with gynecological cancer is limited. The objective of this study was to describe the prevalence of pelvic floor disorders in women with suspected gynecological malignancy before surgery. METHODS: A cross-sectional study was performed of women aged >=18 with a suspected gynecological malignancy who enrolled in the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC) from August 2012 to June 2013. Demographics were obtained from the HR/CSC self reported data; clinical data were abstracted from the electronic medical record. Subjects completed validated questionnaires (Rotterdam Symptom Checklist and the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms) to assess bladder and bowel function. RESULTS: Among 186 women scheduled for surgery for gynecological malignancy, 152 (82 %) completed baseline assessments before surgery. Mean age was 58.1 +/- 13.3 years, and mean BMI was 33.6 +/- 8.8 kg/m(2). The majority of subjects had uterine cancer (61.8 %), followed by ovarian (17.1 %) and cervical (11.1 %). At baseline, the rate of urinary incontinence (UI) was 40.9 %. A third of subjects reported stress UI, and one quarter reported urge UI. The overall rate of fecal incontinence was 3.9 %, abdominal pain was 47.4 %, constipation was 37.7 %, and diarrhea was 20.1 %. When comparing cancer types, there were no differences in pelvic floor symptoms. CONCLUSION: Pelvic floor disorders are common in women with suspected gynecological malignancy at baseline before surgery. Recognizing pelvic floor disorders in the preoperative setting will allow for more individualized, comprehensive care for these women. PMID- 26872647 TI - Natural history of pessary use in women aged 65 - 74 versus 75 years and older with pelvic organ prolapse: a 12-year study. AB - INTRODUCTION AND HYPOTHESIS: The feasibility of use and long-term outcomes of vaginal pessaries for the management of pelvic organ prolapse (POP) in older women remains unknown. Our aim was to determine successful fit rates and outcomes among older women seeking care for POP. METHODS: This was a retrospective cohort study of 304 consecutive women aged 65 years and older with symptomatic POP undergoing a pessary trial at the outpatient urogynecology clinic in Quebec, Canada. Women successfully fitted with a pessary were followed, and survival curves were used to ascertain the median time to pessary discontinuation for women aged 65 to 74 years in comparison with women aged 75 years and older. Long term use was defined as longer than 1 year. Predictors of a successful fitting and long-term discontinuation were ascertained using logistic and Cox regression analyses. RESULTS: Half of the women attempting a pessary trial were aged 75 years and older, and 63 % were fitted successfully regardless of age. Women with a history of hysterectomy or reconstructive pelvic surgery, or those with posterior vaginal wall prolapse were more likely to fail initial insertion. For women aged 65 to 74 years and women aged 75 years and older, the cumulative probabilities of continued pessary use were 87.5 % and 80.8 % at 1 year, 80.6 % and 70.9 % at 2 years, and 62.1 % versus 37.8 % at 5 years. Erosions occurred in 19.3 % of long-term users, with women aged 75 years and older more likely to experience vaginal erosions (HR 3.2, 95 % CI 1.6 - 6.3) and discontinue pessary use. CONCLUSION: Pessary use is a feasible and acceptable treatment option for the long-term management of symptomatic prolapse in over 60 % of all women aged 65 years and older. PMID- 26872648 TI - Potential host-related risk factors for recurrent urinary tract infection in Saudi women of childbearing age. AB - INTRODUCTION AND HYPOTHESIS: Risk factors for recurrent urinary tract infection (rUTI) in women may differ between individuals, age, and the community. This study aimed to evaluate host related risk factors for rUTI in sexually active Saudi women during the childbearing period. METHODS: A case-control study was conducted in five healthcare centers and included married, nonpregnant women aged 18-40 years. A total of 217 women had rUTI (cases) and 252 did not (controls). A validated questionnaire, with a face-to-face interview, was applied to assess various demographic, behavioral, medical, and sexual data. Additionally, a thorough physical examination, saliva and blood analyses, uroflowmetry, and genitourinary ultrasonography were performed. Multivariate logistic regression analysis was used to identify the significant host related risk factors associated with rUTI. RESULTS: In multivariate analysis, attributable risks for rUTI were a history of childhood UTI [odds ratio (OR) = 6.8)] back-to-front douching/wiping after bowel movement (OR = 2.6), younger age at first intercourse (OR = 6.3), increased frequency of sexual intercourse (OR = 4.8), obstructed urinary flow (OR = 1.9), and genital prolapse (OR = 3.4). A total of 9.68 % of cases and none of the controls had high postvoid residual urine (positive predictive value for rUTI = 100 %). CONCLUSIONS: This is the first reported study to evaluate host related risk factors for rUTI in childbearing-age women in Saudi Arabia. Study findings indicate the association between rUTI and various factors that have been already established, with addition of improper rectal hygiene as a potential risk for recurrence. PMID- 26872649 TI - Cauda equina syndrome: an uncommon cause of urinary retention in a young woman. PMID- 26872650 TI - Highlights of the 40th IUGA meeting in Nice, June 2015. PMID- 26872652 TI - Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study. AB - Central nervous system (CNS) involvement in patients with mature B non-Hodgkin lymphoma, post-transplantation proliferative disorder and acute lymphoblastic leukemia confers a significantly inferior prognosis as compared to patients without CNS disease. Intrathecal (IT) or intraventricular administration of rituximab is an option for this group of patients. We report 25 children with CNS involvement of CD20+ B lymphoid malignancies who received in total 163 IT/intraventricular rituximab doses. The median number of doses received by each patient was 6, with a median dose of 25 mg. The most common adverse events were Grades 1 and 2 peripheral neuropathies in five patients (20%), allergy in two patients, and headache in two patients. These events were self-limited, occurring in the 48 hours after treatment and resolving within 24 hr. Three patients presented with more severe though transient side effects, one with a Grade III neuropathy and two with seizure. Eighteen patients (72%) of those treated with IT/intraventricular rituximab, with or without other CNS directed treatment, achieved a CNS remission. This case series suggests that IT/intraventricular rituximab has therapeutic efficacy and relatively limited toxicity. Prospective trials of IT/intraventricular rituximab for patients with CNS involvement of CD20 + B lymphoid malignancies are warranted. PMID- 26872654 TI - The role of the US Great Plains low-level jet in nocturnal migrant behavior. AB - The movements of aerial animals are under the constant influence of atmospheric flows spanning a range of spatiotemporal scales. The Great Plains nocturnal low level jet is a large-scale atmospheric phenomenon that provides frequent strong southerly winds through a shallow layer of the airspace. The jet can provide substantial tailwind assistance to spring migrants moving northward, while hindering southward migration during autumn. This atmospheric feature has been suspected to play a prominent role in defining migratory routes, but the flight strategies used with respect to these winds are yet to be examined. Using collocated vertically pointing radar and lidar, we investigate the altitudinal selection behavior of migrants over Oklahoma during two spring and two autumn migration seasons. In general, migrants choose to fly within the jet in spring, often concentrating in the favorable wind speed maximum. Autumn migrants typically fly below the jet, although some will rapidly climb to reach altitudes above the inhibiting winds. The intensity of migration was relatively constant throughout the spring due to the predominantly favorable southerly jet winds. Conversely, autumn migrants were more apt to delay departure to wait for the relatively infrequent northerly winds. PMID- 26872653 TI - The Link Between Inadequate Sleep and Obesity in Young Adults. AB - The prevalence of obesity has increased dramatically over the past decade. Although an imbalance between caloric intake and physical activity is considered a key factor responsible for the increase, there is emerging evidence suggesting that other factors may be important contributors to weight gain, including inadequate sleep. Overall research evidence suggests that inadequate sleep is associated with obesity. Importantly, the strength and trajectory of the association seem to be influenced by multiple factors including age. Although limited, the emerging evidence suggests young adults might be at the center of a "perfect health storm," exposing them to the highest risk for obesity and inadequate sleep. Unfortunately, the methods necessary for elucidating the complex relationship between sleep and obesity are lacking. Uncovering the underlying factors and trajectories between inadequate sleep and weight gain in different populations may help to identify the windows of susceptibility and to design targeted interventions to prevent the negative impact of obesity and related diseases. PMID- 26872655 TI - Exploratory studies of the potential anti-cancer effects of creatine. AB - Two experiments were performed, in which male Wistar Walker 256 tumor-bearing rats were inoculated with 4 * 10(7) tumor cells subcutaneously and received either creatine (300 mg/kg body weight/day; CR) or placebo (water; PL) supplementation via intragastric gavage. In experiment 1, 50 rats were given PL (n = 22) or CR (n = 22) and a non-supplemented, non-inoculated group served as control CT (n = 6), for 40 days, and the survival rate and tumor mass were assessed. In experiment 2, 25 rats were given CR or PL for 15 days and sacrificed for biochemical analysis. Again, a non-supplemented, non-inoculated group served as control (CT; n = 6). Tumor and muscle creatine kinase (CK) activity and total creatine content, acidosis, inflammatory cytokines, and antioxidant capacity were assessed. Tumor growth was significantly reduced by approximately 30 % in CR when compared with PL (p = 0.03), although the survival rate was not significantly different between CR and PL (p = 0.65). Tumor creatine content tended to be higher in CR than PL (p = 0.096). Tumor CK activity in the cytosolic fraction was higher in CR than PL (p < 0.0001). Blood pCO2 was higher in CT and CR than PL (p = 0.0007 and p = 0.004, respectively). HCO3 was augmented in CT compared to PL (p = 0.03) and CR (p = 0.001). Plasma IL-6 was lower and IL-10 level was higher in CR than PL (p = 0.03 and p = 0.0007, respectively) and TNF-alpha featured a tendency of decrease in CR compared to PL (p = 0.08). Additionally, total antioxidant capacity tended to be lower in CT than PL (p = 0.07). Creatine supplementation was able to slow tumor growth without affecting the overall survival rate, probably due to the re-establishment of the CK-creatine system in cancer cells, leading to attenuation in acidosis, inflammation, and oxidative stress. These findings support the role of creatine as a putative anti-cancer agent as well as help in expanding our knowledge on its potential mechanisms of action in malignancies. PMID- 26872657 TI - Using Object Storage Technology vs Vendor Neutral Archives for an Image Data Repository Infrastructure. AB - The intent of this project was to use object storage and its database, which has the ability to add custom extensible metadata to an imaging object being stored within the system, to harness the power of its search capabilities, and to close the technology gap that healthcare faces. This creates a non-disruptive tool that can be used natively by both legacy systems and the healthcare systems of today which leverage more advanced storage technologies. The base infrastructure can be populated alongside current workflows without any interruption to the delivery of services. In certain use cases, this technology can be seen as a true alternative to the VNA (Vendor Neutral Archive) systems implemented by healthcare today. The scalability, security, and ability to process complex objects makes this more than just storage for image data and a commodity to be consumed by PACS (Picture Archiving and Communication System) and workstations. Object storage is a smart technology that can be leveraged to create vendor independence, standards compliance, and a data repository that can be mined for truly relevant content by adding additional context to search capabilities. This functionality can lead to efficiencies in workflow and a wealth of minable data to improve outcomes into the future. PMID- 26872656 TI - Incorporation of tryptophan analogues into the lantibiotic nisin. AB - Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin. PMID- 26872658 TI - Fully automated calculation of image-derived input function in simultaneous PET/MRI in a sheep model. AB - BACKGROUND: Obtaining the arterial input function (AIF) from image data in dynamic positron emission tomography (PET) examinations is a non-invasive alternative to arterial blood sampling. In simultaneous PET/magnetic resonance imaging (PET/MRI), high-resolution MRI angiographies can be used to define major arteries for correction of partial-volume effects (PVE) and point spread function (PSF) response in the PET data. The present study describes a fully automated method to obtain the image-derived input function (IDIF) in PET/MRI. Results are compared to those obtained by arterial blood sampling. METHODS: To segment the trunk of the major arteries in the neck, a high-resolution time-of-flight MRI angiography was postprocessed by a vessel-enhancement filter based on the inertia tensor. Together with the measured PSF of the PET subsystem, the arterial mask was used for geometrical deconvolution, yielding the time-resolved activity concentration averaged over a major artery. The method was compared to manual arterial blood sampling at the hind leg of 21 sheep (animal stroke model) during measurement of blood flow with O15-water. Absolute quantification of activity concentration was compared after bolus passage during steady state, i.e., between 2.5- and 5-min post injection. Cerebral blood flow (CBF) values from blood sampling and IDIF were also compared. RESULTS: The cross-calibration factor obtained by comparing activity concentrations in blood samples and IDIF during steady state is 0.98 +/- 0.10. In all examinations, the IDIF provided a much earlier and sharper bolus peak than in the time course of activity concentration obtained by arterial blood sampling. CBF using the IDIF was 22 % higher than CBF obtained by using the AIF yielded by blood sampling. CONCLUSIONS: The small deviation between arterial blood sampling and IDIF during steady state indicates that correction of PVE and PSF is possible with the method presented. The differences in bolus dynamics and, hence, CBF values can be explained by the different sampling locations (hind leg vs. major neck arteries) with differences in delay/dispersion. It will be the topic of further work to test the method on humans with the perspective of replacing invasive blood sampling by an IDIF using simultaneous PET/MRI. PMID- 26872660 TI - Different site, different clinical outcomes in perforated colorectal cancer? PMID- 26872659 TI - Risk factors for anastomotic dehiscence in colon cancer surgery--a population based registry study. AB - PURPOSE: The aim of this was to assess potential risk factors for anastomotic dehiscence in colon cancer surgery in a national cohort. METHODS: All patients, who had undergone a resection of a large bowel segment with an anastomosis between 2008 and 2011, were identified in the Swedish Colon Cancer Registry. Patient factors, socioeconomic factors, surgical factors, and medication and hospital data were combined to evaluate risk factors for anastomotic dehiscence. RESULTS: The prevalence of anastomotic dehiscence was 4.3 % (497/11 565). Male sex, ASA classification III-IV, prescribed medications, bleeding more than 300 mL, and uncommon colorectal resections were associated with a higher risk of anastomotic dehiscence. Hospital stay was increased with 14.5 days, and 30-day mortality as well as long-term mortality was higher in the anastomotic dehiscence group. CONCLUSIONS: There are several factors that are possible to know preoperatively or during surgery that can indicate whether an anastomosis is an appropriate option. Anastomotic dehiscence increases hospital stay and long-term mortality. PMID- 26872661 TI - Erratum to: Outcome for stage II and III rectal and colon cancer equally good after treatment improvement over three decades. PMID- 26872662 TI - MRI abnormalities found 1 year prior to symptom onset in a case of Creutzfeldt Jakob disease. PMID- 26872663 TI - Hypospadias as a novel feature in spinal bulbar muscle atrophy. AB - Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA. PMID- 26872664 TI - Endovascular mechanical thrombectomy in basilar artery occlusion: variables affecting recanalization and outcome. AB - Ischemic stroke due to basilar artery occlusion (BAO) is frequently associated with a poor prognosis. To date the most effective therapeutic approach has not been established and little is known about the predictors of clinical outcome. The aim of this study was to describe safety and efficacy of intra-arterial mechanical thrombectomy (IAMT) through latest generation devices in patients with BAO, focusing on those variables that may affect recanalization and clinical outcome. We analyzed retrospectively a series of 32 patients with BAO who underwent IAMT. We assessed the association of some clinical and neuroradiological features with recanalization rate and clinical outcome. Successful recanalization was achieved in 28 out of 32 patients (87.5 %). Symptomatic intracerebral hemorrhage (SICH) was observed in 2/32 patients (6.3 %) and mortality in the first 3 months was 25.0 %. At 3-month follow up evaluation, 13/32 patients (40.6 %) showed a good functional outcome (mRS score <=2). There were no statistical differences in term of age, gender, risk factors, cause of stroke, recanalization rate, pre-treatment pc-ASPECTS score and SICH frequencies between patients with favorable and unfavorable outcome. Increased length of thrombi was associated with unfavorable clinical outcome at 3 months. Recanalization rate was not affected by any of the variables considered. In BAO, IAMT through newest generation devices has high recanalization rates and low complication frequencies. Length of BAO is an important predictor of clinical outcome. PMID- 26872665 TI - Neurological diseases and health care utilization among first-generation immigrants. AB - Migrants may constitute a risk group and should have specific targets for health policy. To identify their health needs, it is important to investigate their epidemiological profile and their access to health services. The aim of this study was to identify the pattern of hospital and neurological services use among immigrants living in Brescia (Italy). The analysis took into account the records of 45,645 immigrants admitted to the ER (Emergency Room) as well as the discharge data of 6419 patients hospitalized in the Department of Neurology of the Azienda Ospedaliera Spedali Civili di Brescia, over a 3.5 years period. To take confounding factors into account, immigrant patients admitted to the department of Neurology were compared to a selection of Italian patients matched by age and sex. The main objectives were to explore causes of admission of the immigrant population-along with socio-demographic characteristics-to the Emergency Room and to the Neurology Units. Immigrants showed a similar pattern of hospital use to the Italian patients, although with a higher frequency of infective diseases and traumatic injuries. They also showed a higher mean Diagnosis-Related Group (DRG) weight than the Italians. Average length of hospitalization was longer in immigrant population. However, the use of neurological services by migrants is less than their demographic share. Poorer economic and social conditions, as well as a worse labor market experienced by immigrants may expose them to risk factors for injuries and infective diseases. Reducing the language and bureaucratic barriers, as well as enhancing cross-cultural skills of physicians, might be crucial in decreasing the length and the cost of hospitalization. PMID- 26872666 TI - Subacute progressive aphasia: a rare presentation of Creutzfeldt-Jakob disease. PMID- 26872668 TI - Vladimir K. Roth (1848-1916). PMID- 26872667 TI - Absence of MxA induction is related to a poor clinical response to interferon beta treatment in multiple sclerosis patients. AB - The aim of this study is to investigate whether induction of myxovirus resistance protein A (MxA) mRNA after 3 months of interferon-beta administration is related to the treatment response in multiple sclerosis (MS) patients. In this prospective study, MS patients were enrolled before starting treatment. Demographic, clinical and radiological variables were recorded. Blood samples were obtained before, and at 3 and 12 months after interferon-beta treatment. Real-time PCR was used to analyze MxA mRNA expression. Patients were classified as MxA-low or -high depending on MxA levels at baseline, and as MxA-induced or non-induced according to whether an increase in MxA expression was detected at month 3. Time to the next relapse was investigated using Cox proportional hazards regression analysis. One hundred and four patients were selected and followed for a median of 2.2 years (IQR 1.6-3.5). On Cox regression analysis, a higher EDSS score before treatment (HR 1.57; 95 % CI 1.02-2.40; p = 0.039), MxA-high status at baseline (HR 2.71; 95 % CI 1.26-5.81; p = 0.010), and MxA-non-induced at month 3 (HR 2.49; 95 % CI 1.08-5.68; p = 0.031), were predictors of poor response to interferon-beta in naive MS patients. Patients showing a lower capacity for MxA induction following 3 months of interferon-beta treatment are more likely to be non-responders to this therapy. PMID- 26872671 TI - Modulation of central nystagmus by vision, proprioception, and efference copy signals: a systematic evaluation. AB - Non-vestibular sensorimotor signals modulate the vestibular nucleus neuron to achieve current behavioral goals, and may generate or modulate nystagmus. In central lesions affecting the vestibular nuclei, non-vestibular signals such as mastication or swallowing may induce nystagmus. However, the influence of non vestibular signals on these types of nystagmus has not been investigated in a systematic way and the underlying mechanisms of the modulation are poorly understood. In this study, several non-vestibular sensorimotor stimuli were applied to evaluate the patterns of nystagmus modulation in a patient with suspected rhombencephalitis or imaging negative small infarction, probably involving the left dorsolateral medulla. The nystagmus was induced or significantly modulated by (1) visual inputs, and (2) combined proprioceptive and efference copy signals (during voluntary motion) unrelated to body or head orientation. In contrast, isolated proprioceptive signal, mental set, or non proprioceptive somatosensory inputs showed a negligible effect on the induction of nystagmus. Based on these modulations, we suggest that (1) the visually mediated nystagmus is due to a lesion-induced pursuit asymmetry, and (2) the nystagmus induced during voluntary motion is due to erroneous contribution of combined proprioceptive and efference copy signals during integration of non vestibular signals for ocular motor control. Various non-vestibular sensorimotor stimulations may induce nystagmus due to dysfunction of the central vestibular neural circuity. PMID- 26872669 TI - Immune-mediated processes in neurodegeneration: where do we stand? AB - Neurodegeneration is a pathological condition that predominantly affects neurons. It represents a large spectrum of disorders with heterogeneous symptoms and distinct clinical features. In addition to the devastating effects it can have on the affected individual, it constitutes a heavy burden to the society in terms of health care costs. Although the exact cause of neurodegeneration is not known, there are plenty of evidences supporting the notion that the immune system is strongly associated with various forms of neurodegenerative diseases. Given the numerous functions of immune cells, a change in their expression can either be beneficial or deleterious to the host. A better understanding of the molecular and cellular processes in neurodegeneration is therefore needed. This could facilitate the development of new therapeutic targets and provide effective means to dampen the progression of neurodegenerative disorders. The overarching aim of this paper is to provide an overview of the roles that the innate and adaptive immune systems play in the central nervous system, and to discuss their beneficial or detrimental effects during neurodegeneration. This paper also critically examines the contribution of immune and inflammatory-mediated responses in the development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyloid lateral sclerosis by illustrating key findings from animal and human studies. PMID- 26872670 TI - The role of mutations in COL6A3 in isolated dystonia. AB - Specific mutations in COL6A3 have recently been reported as the cause of isolated recessive dystonia, which is a rare movement disorder. In all patients, at least one mutation was located in Exons 41 and 42. In an attempt to replicate these findings, we assessed by direct sequencing the frequency of rare variants in Exons 41 and 42 of COL6A3 in 955 patients with isolated or combined dystonia or with another movement disorder with dystonic features. We identified nine heterozygous carriers of rare variants including five different missense mutations and an extremely rare synonymous variant. In these nine patients, we sequenced the remaining 41 coding exons of COL6A3 to test for a second mutation in the compound heterozygous state. In only one of them, a second rare variant was identified (Thr732Met + Pro3082Arg). Of note, this patient had been diagnosed with Parkinson's disease (with dystonic posturing) due to homozygous PINK1 mutations. The COL6A3 mutations clearly did not segregate with the disease in the four affected siblings of this family. Further, there was no indication for a disease-modifying effect of the COL6A3 mutations since disease severity or age at onset did not correlate with the number of COL6A3 mutated alleles in this family. In conjunction with the relatively high frequency of homozygous carriers of reported mutations in publically available databases, our data call a causal role for variants in COL6A3 in isolated dystonia into question. PMID- 26872672 TI - Necroptotic cell death in failing heart: relevance and proposed mechanisms. AB - As cardiomyocytes have a limited capability for proliferation, renewal, and repair, the loss of heart cells followed by replacement with fibrous tissue is considered to result in the development of ventricular dysfunction and progression to heart failure (HF). The loss of cardiac myocytes in HF has been traditionally believed to occur mainly due to programmed apoptosis or unregulated necrosis. While extensive research work is being carried out to define the exact significance and contribution of both these cell death modalities in the development of HF, recent knowledge has indicated the existence and importance of a different form of cell death called necroptosis in the failing heart. This new cell damaging process, resembling some of the morphological features of passive necrosis as well as maladaptive autophagy, is a programmed process and is orchestrated by a complex set of proteins involving receptor-interacting protein kinase 1 and 3 (RIP1, RIP3) and mixed lineage kinase domain-like protein (MLKL). Activation of the RIP1-RIP3-MLKL signaling pathway leads to disruption of cation homeostasis, plasma membrane rupture, and finally cell death. It seems likely that inhibition of any site in this pathway may prove as an effective pharmacological intervention for preventing the necroptotic cell death in the failing heart. This review is intended to describe general aspects of the signaling pathway associated with necroptosis, to describe its relationship with cardiac dysfunction in some models of cardiac injury and discuss its potential relevance in various types of HF with respect to the underlying pathologic mechanisms. PMID- 26872673 TI - The role of inflammation and cell death in the pathogenesis, progression and treatment of heart failure. AB - Chronic inflammation underlies a variety of seemingly unrelated conditions including coronary artery disease. The interest in exploring the role of inflammation in heart failure (CHF) arises from earlier observations that circulating pro-inflammatory biomarker levels are elevated in patients with both ischaemic and non-ischaemic cardiomyopathies and correlate with severity of disease and prognosis (McMurray et al. in Eur Heart J 33:1787-1847, 2012; Mosterd and Hoes in Heart 93:1137-1146, 2007; Owan et al. in New Engl J Med 355:251-259, 2006). In acute decompensated HF, pro-inflammatory biomarker levels have been associated with mortality and readmission rates (Cowie et al. in Heart 83:505 510, 2000). Similar to neurohormonal activation and inflammation, production of pro-inflammatory cytokines is a response to stress in an attempt to restore cellular function. However, sustained expression and exposure to cytokines can lead to left ventricular dysfunction, negative inotropic effects, altered cardiac metabolism, myocardial remodelling and HF progression. However, it is unclear whether elevated levels of pro-inflammatory biomarkers, such as high-sensitivity C-reactive protein, signify an ongoing inflammatory process that leads to HF progression, or are merely markers of advanced disease. Beta-blockers, renin angiotensin-aldosterone axis antagonists, statins and immunosuppressants have been found to decrease the levels of cytokines in small clinical studies of patients with HF (Hobbs et al. in Heart J 28:1128-1134, 2007). However, 'immunomodulatory' approaches applied in the RECOVER, RENAISSANCE, ATTACH, IMAC and ACCLAIM double-blind, placebo-controlled studies had neutral or negative effects on outcomes of patients with HF. In the present review, we focus on the role of inflammation in pathogenesis and progression of the HF, the value of pro inflammatory cytokines as biomarkers and the potential therapeutic applications of immunomodulation in HF patients. PMID- 26872675 TI - Role of cell death in the progression of heart failure. AB - All multicellular organisms develop during evolution the highly regulated and interconnected pathways of cell death. This complex network contributes to the pathogenesis of various cardiovascular disorders including ischemia/reperfusion injury, myocardial infarction, heart failure, dysrhythmias and atherosclerosis. Chronic cardiac remodeling response and transition to overt HF have been associated with modestly increased apoptosis, although the actual burden of chronic cell loss attributable to apoptosis is not clear. Central mediators of cardiomyocyte survival and death are the mitochondrial organelles. Based on its morphological characteristics, cell death can be classified into three major types: apoptosis, necrosis and autophagy. Recently, a new pathway of regulated necrosis, necroptosis, has also been reported in the failing heart. The mitochondrial (intrinsic) and the death-receptor-mediated (extrinsic) converge at mitochondria inducing release of mitochondrial apoptogens to initiate the caspase cascade and eventually degradation of the doomed cardiomyocyte. Activation of death receptors can initiate not only extrinsic apoptotic pathway, but also necrosis. On the other hand, autophagy, which is characterized by the massive formation of lysosomal-derived vesicles, containing degenerating cytoplasmic contents, is primarily a survival response to nutrient deprivation, and a selective form of autophagy, mitophagy, is also a protective mechanism that allows to eliminate damaged mitochondria and thereby to attenuate mitochondria mediated apoptosis and necrosis in the myocardium. Further insight into the molecular mechanisms underlying cell death will increase the efficiency and repertoire of therapeutic interventions available in cardiovascular disease. PMID- 26872674 TI - Mitochondrial dynamics and cell death in heart failure. AB - The highly regulated processes of mitochondrial fusion (joining), fission (division) and trafficking, collectively called mitochondrial dynamics, determine cell-type specific morphology, intracellular distribution and activity of these critical organelles. Mitochondria are critical for cardiac function, while their structural and functional abnormalities contribute to several common cardiovascular diseases, including heart failure (HF). The tightly balanced mitochondrial fusion and fission determine number, morphology and activity of these multifunctional organelles. Although the intracellular architecture of mature cardiomyocytes greatly restricts mitochondrial dynamics, this process occurs in the adult human heart. Fusion and fission modulate multiple mitochondrial functions, ranging from energy and reactive oxygen species production to Ca(2+) homeostasis and cell death, allowing the heart to respond properly to body demands. Tightly controlled balance between fusion and fission is of utmost importance in the high energy-demanding cardiomyocytes. A shift toward fission leads to mitochondrial fragmentation, while a shift toward fusion results in the formation of enlarged mitochondria and in the fusion of damaged mitochondria with healthy organelles. Mfn1, Mfn2 and OPA1 constitute the core machinery promoting mitochondrial fusion, whereas Drp1, Fis1, Mff and MiD49/51 are the core components of fission machinery. Growing evidence suggests that fusion/fission factors in adult cardiomyocytes play essential noncanonical roles in cardiac development, Ca(2+) signaling, mitochondrial quality control and cell death. Impairment of this complex circuit causes cardiomyocyte dysfunction and death contributing to heart injury culminating in HF. Pharmacological targeting of components of this intricate network may be a novel therapeutic modality for HF treatment. PMID- 26872677 TI - Chest wall motion analysis in healthy volunteers and adults with cystic fibrosis using a novel Kinect-based motion tracking system. AB - Respiratory disease is the leading cause of death in the UK. Methods for assessing pulmonary function and chest wall movement are essential for accurate diagnosis, as well as monitoring response to treatment, operative procedures and rehabilitation. Despite this, there is a lack of low-cost devices for rapid assessment. Spirometry is used to measure air flow expired, but cannot infer or directly measure full chest wall motion. This paper presents the development of a low-cost chest wall motion assessment system. The prototype was developed using four Microsoft Kinect sensors to create a 3D time-varying representation of a patient's torso. An evaluation of the system in two phases is also presented. Initially, static volume of a resuscitation mannequin with that of a Nikon laser scanner is performed. This showed the system has slight underprediction of 0.441 %. Next, a dynamic analysis through the comparison of results from the prototype and a spirometer in nine cystic fibrosis patients and thirteen healthy subjects was performed. This showed an agreement with correlation coefficients above 0.8656 in all participants. The system shows promise as a method for assessing respiratory disease in a cost-effective and timely manner. Further work must now be performed to develop the prototype and provide further evaluations. PMID- 26872679 TI - Value of preoperative 3T multiparametric MRI for surgical margin status in patients with prostate cancer. AB - PURPOSE: To examine the value of preoperative multiparametric magnetic resonance imaging (MRI) as a predictor of surgical margin (SM) status in patients with prostate cancer (PC). MATERIALS AND METHODS: The Institutional Review Board approved this retrospective study; the requirement for informed consent was waived. Fifty-six male patients with histologically proven PC underwent preoperative 3T multiparametric MRI including high b value (0, 2000 s/mm(2) ) diffusion-weighted imaging. In each patient, clinical data, such as biopsy Gleason score and D'Amico clinical risk score, and multiparametric MRI findings, such as tumor location, tumor size, tumor extension in the apical or proximal region, tumor apparent diffusion coefficient (ADC), and the presence or absence of MRI findings of extracapsular extension (ECE) were evaluated. Statistical evaluations included the Fisher's exact test, chi(2) test, Mann-Whitney U-test, and logistic regression analysis. RESULTS: On histopathological evaluation, 15 patients (27%) were SM-positive (SMP group), and 41 (73%) were SM-negative (SMN group). The tumor ADC was significantly lower in the SMP group than in the SMN group (P = 0.001). The frequency of tumor extension in the apex or base and suspected ECE on MRI were significantly higher in the SMP group than in the SMN group (P = 0.037 and 0.011, respectively). On multivariate analysis, tumor ADC was the only predictor of SM status in PC (P = 0.003). CONCLUSION: PC with positive SM was characterized by tumor extension in the apical and proximal regions, lower tumor ADC, and tumors with positive MRI findings of ECE, compared to tumors with negative SM. J. Magn. Reson. Imaging 2016;44:584-593. PMID- 26872676 TI - Atrophied cardiomyocytes and their potential for rescue and recovery of ventricular function. AB - Cardiomyocytes must be responsive to demands placed on the heart's contractile work as a muscular pump. In turn, myocyte size is largely dependent on the workload they perform. Both hypertrophied and atrophic myocytes are found in the normal and diseased ventricle. Individual myocytes become atrophic when encumbered by fibrillar collagen, such as occurs at sites of fibrosis. The mechanisms include: (a) being immobilized and subject to disuse with ensuing protein degradation mediated by redox-sensitive, proteolytic ligases of the ubiquitin-proteasome system and (b) dedifferentiated re-expressing fetal genes induced by low intracellular triiodothyronine (T3) via thyroid hormone receptor beta1. This myocyte-selective, low T3 state is a consequence of heterocellular signaling emanating from juxtaposed scar tissue myofibroblasts and their secretome with its de novo generation of angiotensin II. In a paracrine manner, angiotensin II promotes myocyte Ca(2+) entry and subsequent Ca(2+) overload with ensuing oxidative stress that overwhelms antioxidant defenses to activate deiodinase-3 and its enzymatic degradation of T3. In the failing heart, atrophic myocytes represent an endogenous population of viable myocytes which could be rescued to augment contractile mass, reduce systolic wall stress (afterload) and recover ventricular function. Experimental studies have shown the potential for the rescue and recovery of atrophic myocytes in rebuilding the myocardium--a method complementary to today's quest in regenerating myocardium using progenitor cells. PMID- 26872678 TI - Nonnegative matrix factorization and sparse representation for the automated detection of periodic limb movements in sleep. AB - Stroke is a leading cause of death and disability in adults, and incurs a significant economic burden to society. Periodic limb movements (PLMs) in sleep are repetitive movements involving the great toe, ankle, and hip. Evolving evidence suggests that PLMs may be associated with high blood pressure and stroke, but this relationship remains underexplored. Several issues limit the study of PLMs including the need to manually score them, which is time-consuming and costly. For this reason, we developed a novel automated method for nocturnal PLM detection, which was shown to be correlated with (a) the manually scored PLM index on polysomnography, and (b) white matter hyperintensities on brain imaging, which have been demonstrated to be associated with PLMs. Our proposed algorithm consists of three main stages: (1) representing the signal in the time-frequency plane using time-frequency matrices (TFM), (2) applying K-nonnegative matrix factorization technique to decompose the TFM matrix into its significant components, and (3) applying kernel sparse representation for classification (KSRC) to the decomposed signal. Our approach was applied to a dataset that consisted of 65 subjects who underwent polysomnography. An overall classification of 97 % was achieved for discrimination of the aforementioned signals, demonstrating the potential of the presented method. PMID- 26872681 TI - Elicited versus emitted behavior: Time to abandon the distinction. AB - The concept of emitted behavior was formulated as a part of the original argument for the validity of a new kind of learning called operant conditioning. The rationale for operant conditioning contrasted it with Pavlovian or classical conditioning, which was (and remains) fundamentally based on responses to conditioned and unconditioned stimuli. Classical conditioned responses were said to be elicited. In contrast, operant behavior was viewed as emitted and controlled primarily by response consequences rather than antecedents. I argue that the distinction between emitted and elicited behavior is no longer warranted for three major reasons. First, the distinction was based on a view of Pavlovian conditioning that is no longer viable. Second, the distinction is incompatible with both empirical data and contemporary conceptualizations of operant behavior. Third, the only way to overcome these problems is to define emitted and elicited in terms of the type of conditioning (operant and classical) that produces these behaviors, but that approach makes the definitions circular and does not avoid implications of the terms that are misleading and counterproductive in light of contemporary research and thinking. PMID- 26872680 TI - Classification and treatment of distal radius fractures: a survey among orthopaedic trauma surgeons and residents. AB - PURPOSE: Classification, the definition of an acceptable reduction and indications for surgery in distal radius fracture management are still subject of debate. The purpose of this study was to characterise current distal radius fracture management in Europe. METHODS: During the European Congress of Trauma and Emergency Surgery (ECTES) 2015 a 20-question multiple-choice survey was conducted among the attending surgeons and residents of the hand and wrist session. Consensus was defined as more than 50 % identical answers (moderate consensus 50-75 % and high consensus more than 75 %). RESULTS: A total of 46 surgeons and residents participated in the survey. High consensus was found among both surgeons and residents for defining the AO/OTA classification as the preferred classification system. For the definition of an acceptable reduction, a moderate to high consensus could be determined. Overall, high consensus was found for non-operative treatment instead of operative treatment in dislocated extra- and intra-articular distal radius fractures with an acceptable closed reduction, regardless of age. We found high (surgeons) and moderate (residents) consensus on the statement that an intra-articular gap or step-off >=2 mm, in patients younger than 65 years, is an absolute indication for ORIF. The same applied for ORIF in dislocated fractures without an acceptable closed reduction in patients younger than 75 years of age. CONCLUSION: Current distal radius fracture management in Europe is characterised by a moderate to high consensus on the majority of aspects of fracture management. PMID- 26872682 TI - Key players in neurodegenerative disorders in focus-New insights into the proteomic profile of Alzheimer's disease, schizophrenia, ALS, and multiple sclerosis-24th HUPO BPP Workshop: September 29, 2015, Vancouver, Canada. AB - The HUPO Brain Proteome Project (HUPO BPP) held its 24th workshop in Vancouver, Canada, September 29, 2015. The focus of the autumn workshop was on new insights into the proteomic profile of Alzheimer's disease, schizophrenia, ALS and multiple sclerosis. PMID- 26872683 TI - Current Updates on Classification, Diagnosis and Treatment of Hemophagocytic Lymphohistiocytosis (HLH). AB - Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyperinflammatory syndrome characterized by excessive activation of macrophages and T cells resulting from defective cytotoxicity. Severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and histiocytes (macrophages) secreting high amounts of inflammatory cytokines threatens the life of the patient and may lead to death unless arrested by appropriate treatment. HLH can be caused either by certain underlying genetic diseases (familial HLH), or may also occur due to particular triggers in patients with no known inherited disorder (acquired HLH). Due to life threatening nature of the disease, early diagnosis and initiation of immunosuppressive therapy is extremely important. HLH diagnosis is based on constellation of clinical manifestations and laboratory parameters which often overlap with those of severe infection or sepsis. Identification of patients with familial HLH and their underlying genetic defects requires specialized laboratory tests and is important for predicting relapses and planning early therapeutic hematopoietic stem cell transplantation (HSCT). A high suspicion and thorough clinical, immunological and genetic work-up is required for diagnosis of HLH. Prompt initiation of adequate treatment is essential for the survival. Substantial progress has been made in exploring the complex cause and pathophysiology of HLH and also in management of HLH patients. PMID- 26872684 TI - Next Generation Sequencing in the Clinic. PMID- 26872685 TI - Distinct oxidative cleavage and modification of bovine [Cu- Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule. AB - We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and alpha-amidation pathways, respectively. The three dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5A from the alpha-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. PMID- 26872686 TI - Extending the spectrum of AKT1 mosaicism: not just the Proteus syndrome. PMID- 26872687 TI - Audible blink in prostaglandin-associated periorbitopathy. PMID- 26872688 TI - Trachyonychia as the presenting sign of myeloma-associated amyloidosis. PMID- 26872689 TI - Age-related optimization of screw placement for reduced loosening risk in locked plating. AB - When using locked plating for bone fracture fixation, screw loosening is reported as one of the most frequent complications and is commonly attributed to an incorrect choice of screw configuration. Choosing a patient-optimized screw configuration is not straightforward as there are many interdependent variables that affect device performance. The aim of the study was to evaluate the influence that locking screw configuration has on loosening risk and how this is influenced by bone quality. This study uses finite element models that incorporate cortical bone heterogeneity, orthotropy, and geometrical nonlinearity to examine the effect of screw configuration on variables associated with loosening and interfragmentary motion. Strain levels within the bone were used as indicators of regions that may undergo loosening. The study found that, in healthy bone under axial loading, the most important variables influencing strain levels within the bone were the size of the bridging span (working length) and the plate rigidity. Unlike healthy bone, osteoporotic bone was found to be particularly sensitive to the spacing of the screws within the plate. Using two empty screw holes between the screws closest to the fracture was found to reduce the strain levels at the first screw by 49% in osteoporotic bone (compared to only 2.4% in healthy bone). The study also found that under torsional loading the total number of screws used was the most important variable with a 59% reduction in the strain around the screws closest to the fracture when using six rather than four screws in osteoporotic bone. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1856-1864, 2016. PMID- 26872690 TI - Development and validation of a theoretical test in non-anaesthesiologist administered propofol sedation for gastrointestinal endoscopy. AB - OBJECTIVE: Safety with non-anaesthesiologist-administered propofol sedation (NAAP) during gastrointestinal (GI) endoscopy is related to theoretical knowledge. A summative testing of knowledge before attempting supervised nurse administered propofol sedation (NAPS) in the clinic is advised. The aims of this study were to develop a theoretical test about propofol sedation, to gather validity evidence for the test and to measure the effect of a NAPS-specific training course. MATERIAL AND METHODS: A three-phased psychometric study on multiple choice questionnaire (MCQ) test development, gathering of validity evidence and evaluation of the effect of a specific NAAP course on the test result. A MCQ containing 86 questions was developed and administered 113 times to 91 participants representing novices, intermediates and experienced. RESULTS: Question difficulty analyses revealed 50 level I and II questions. The 50 MCQs showed mean (SD) intergroup differences (p = 0.001) between novices = 28.6 (4.82), intermediates = 36.8 (5.43) and experienced = 41.8 (4.65) and provided a pass score of 35.2. The course with pre-course test had significant effect on the knowledge of nurses (18% increase) and physicians (19% increase; p = 0.001 and 0.001, respectively). CONCLUSIONS: Data supported the validity of the developed MCQ test. The NAPS-specific course with pre-course testing adds theoretical knowledge to already well-prepared participants. PMID- 26872691 TI - PDD-5S: A useful screening tool for Parkinson's disease dementia. AB - INTRODUCTION: Parkinson's disease dementia (PDD) contributes to poor quality of life and increases the mortality risk. Early detection and diagnosis of PDD are essential for clinical care. METHODS: We recruited patients with idiopathic Parkinson's disease (PD), who underwent clinical assessments and neuropsychological tests, at 12 teaching hospitals in Taiwan. Probable PDD was diagnosed according to the Movement Disorder Society Task Force clinical criteria. Using binary logistic regression, we selected significant items from an original 30-item informant questionnaire. We utilized these items, along with a simple cognitive test, to discriminate between PDD and nondemented PD (PD-ND). RESULTS: Among the 265 PD patients (156 men, 109 women, mean age 71.9 +/- 9.1 years), 102 and 163 patients were diagnosed with probable PDD and PD-ND, respectively. The mean education of participants was 8.8 +/- 5.3 years, and the mean disease duration was 5.5 +/- 5.4 years. When the patients fulfilled either of the following criteria: (1) a score >= 3 for the five endorsed screening questions, (2) a score of 1-2 for the five above screening questions combined with a score <= 10 items for category verbal fluency, the sensitivity and specificity of the PDD screening tool were 80.4% and 80.4%, respectively. The area under the receiver operating characteristic curve (AUC) was 0.804. We tested this screening tool in another 137 unrelated PD patients and the sensitivity, specificity, and AUC were 77.4%, 96.4%, and 0.869, respectively. CONCLUSION: The "PDD-5S" is a brief and useful screening tool for PDD. PMID- 26872692 TI - Predictors of dual control of HIV and diabetes. AB - Diabetes is one of the most frequently diagnosed comorbidities in individuals living with HIV. Dual control of both conditions is essential because both diseases negatively impact the immune and vascular systems. The purpose of this retrospective study was to assess the factors associated with dual control of HIV and diabetes. Patients from a large urban Ryan White-funded HIV clinic with a diagnosis of diabetes were identified; inclusion criteria comprised age over 25 years, use of antiretroviral therapy for at least 6 months, and a diagnosis of diabetes. Optimal control was described as a non-detectable viral load (i.e. log10 HIV1-viral load <1.6) and HbA1c <=7%. Fewer than half of 186 patients had optimal control of HIV and diabetes. Direct logistic regression using backward stepwise entry identified three variables that significantly fit the model: age, insulin-based therapy, and African-American race. The full model was statistically significant. As patients with HIV now live longer, more effort needs to be given to adherence to improve health outcomes for co-morbidities. PMID- 26872693 TI - Evaluation of risk factors for high flow nasal oxygen failure: a means to avoid disillusion. PMID- 26872696 TI - Erythropoeitin Signaling in Macrophages Promotes Dying Cell Clearance and Immune Tolerance. AB - The failure of apoptotic cell clearance is linked to autoimmune diseases, nonresolving inflammation, and developmental abnormalities; however, pathways that regulate phagocytes for efficient apoptotic cell clearance remain poorly known. Apoptotic cells release find-me signals to recruit phagocytes to initiate their clearance. Here we found that find-me signal sphingosine 1-phosphate (S1P) activated macrophage erythropoietin (EPO) signaling promoted apoptotic cell clearance and immune tolerance. Dying cell-released S1P activated macrophage EPO signaling. Erythropoietin receptor (EPOR)-deficient macrophages exhibited impaired apoptotic cell phagocytosis. EPO enhanced apoptotic cell clearance through peroxisome proliferator activated receptor-gamma (PPARgamma). Moreover, macrophage-specific Epor(-/-) mice developed lupus-like symptoms, and interference in EPO signaling ameliorated the disease progression in lupus-like mice. Thus, we have identified a pathway that regulates macrophages to clear dying cells, uncovered the priming function of find-me signal S1P, and found a role of the erythropoiesis regulator EPO in apoptotic cell disposal, with implications for harnessing dying cell clearance. PMID- 26872694 TI - In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity. AB - According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL) mediated killing of virus-infected cells in vivo remains elusive. We used two photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity. PMID- 26872695 TI - The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. AB - Exposure to a plethora of environmental challenges commonly triggers pathological type 2 cell-mediated inflammation. Here we report the pathological role of the Wnt antagonist Dickkopf-1 (Dkk-1) upon allergen challenge or non-healing parasitic infection. The increased circulating amounts of Dkk-1 polarized T cells to T helper 2 (Th2) cells, stimulating a marked simultaneous induction of the transcription factors c-Maf and Gata-3, mediated by the kinases p38 MAPK and SGK 1, resulting in Th2 cell cytokine production. Circulating Dkk-1 was primarily from platelets, and the increase of Dkk-1 resulted in formation of leukocyte platelet aggregates (LPA) that facilitated leukocyte infiltration to the affected tissue. Functional inhibition of Dkk-1 impaired Th2 cell cytokine production and leukocyte infiltration, protecting mice from house dust mite (HDM)-induced asthma or Leishmania major infection. These results highlight that Dkk-1 from thrombocytes is an important regulator of leukocyte infiltration and polarization of immune responses in pathological type 2 cell-mediated inflammation. PMID- 26872697 TI - Interleukin-35 Limits Anti-Tumor Immunity. AB - Regulatory T (Treg) cells pose a major barrier to effective anti-tumor immunity. Although Treg cell depletion enhances tumor rejection, the ensuing autoimmune sequelae limits its utility in the clinic and highlights the need for limiting Treg cell activity within the tumor microenvironment. Interleukin-35 (IL-35) is a Treg cell-secreted cytokine that inhibits T cell proliferation and function. Using an IL-35 reporter mouse, we observed substantial enrichment of IL-35(+) Treg cells in tumors. Neutralization with an IL-35-specific antibody or Treg cell restricted deletion of IL-35 production limited tumor growth in multiple murine models of human cancer. Limiting intratumoral IL-35 enhanced T cell proliferation, effector function, antigen-specific responses, and long-term T cell memory. Treg cell-derived IL-35 promoted the expression of multiple inhibitory receptors (PD1, TIM3, LAG3), thereby facilitating intratumoral T cell exhaustion. These findings reveal previously unappreciated roles for IL-35 in limiting anti-tumor immunity and contributing to T cell dysfunction in the tumor microenvironment. PMID- 26872700 TI - Relationship between blood eosinophils and clinical characteristics in a cross sectional study of a US population-based COPD cohort. AB - BACKGROUND: Current evidence suggests that blood eosinophil levels (Eos) are associated with chronic obstructive pulmonary disease (COPD) treatment response and natural history. This analysis investigated the relationship between Eos levels and clinical characteristics in a representative cohort of US subjects with spirometry-defined COPD. METHODS: Cross-sectional data from the National Health And Nutrition Examination Survey (NHANES 2007-2010) of subjects >= 40 years with spirometry-defined COPD and Eos data (n = 948) were analyzed. Differences in clinical characteristics by Eos level (<= 2%, > 2%) were compared using chi-square tests. Characteristics associated with Eos > 2% were identified using multivariate logistic regression modeling. Characteristics associated with Eos >2% among subjects with normal lung function, plus other cut-points among the COPD population, were evaluated post hoc. FINDINGS: Most participants had Eos >2%; 70.7% with spirometry-defined COPD and 65.5% with normal lung function. Older age, male gender, and severe current asthma were significantly associated with Eos >2% in COPD subjects. The Eos <= 2% COPD group had higher reported rates of previous heart attack and anemia. Among participants with normal lung function, Eos > 2% was associated with being male, being overweight/obese, older age, hay fever, and congestive heart failure. INTERPRETATION: In this large US based cohort, Eos > 2% was prevalent in participants with COPD and normal lung function. Among participants with COPD, Eos > 2% was associated with specific characteristics including lower rates of some co-morbidities; however, the clinical implications and relationships between Eos levels, COPD mechanisms, and risk of outcomes require further evaluation. PMID- 26872701 TI - Positive effect of probiotic Lactobacillus plantarum in reversing LPS-induced infertility in a mouse model. AB - Bacterial infections have high incidence among the female population at reproductive age and are widely known to cause infertility due to inflammation. The purpose of the present study was to investigate the effect of the inflammatory agent LPS on fertility outcome and to evaluate the ability of Lactobacillus plantarum in ameliorating the LPS-mediated inflammation-induced infertility. Female BALB/c mice infused intravaginally with a single dose of 20 MUl sterile normal saline containing 5, 10 or 20 MUg LPS were divided into two groups for evaluation of tissue histology and pregnancy outcome. In the first group, aimed at observing changes in tissue histology, inflammation was observed in vaginal sections of mice instilled with a single dose of 20 MUg LPS, which were sacrificed on days 2, 5 and 8. In the second group, aimed at evaluating pregnancy outcome, female mice were administered 20 MUg LPS, which rendered them infertile upon mating on days 2, 5 and 8. In another experiment, normal histology of vaginal sections was observed in mice administered a single dose of 20 MUg LPS, followed by 108 c.f.u. L. plantarum in 20 MUl at 24 h intervals, until the mice were sacrificed on days 2, 5 and 8. Following similar treatment, female mice, when mated with proven male breeder mice on days 2, 5 and 8, retained their fertility and delivered pups. These results were further confirmed by the downregulation of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines on treatment with L. plantarum, revealing the role of probiotics in ameliorating inflammation-induced infertility. PMID- 26872698 TI - Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. AB - Checkpoint blockade immunotherapies can be extraordinarily effective, but might benefit only the minority of patients whose tumors are pre-infiltrated by T cells. Here, using lung adenocarcinoma mouse models, including genetic models, we show that autochthonous tumors that lacked T cell infiltration and resisted current treatment options could be successfully sensitized to host antitumor T cell immunity when appropriately selected immunogenic drugs (e.g., oxaliplatin combined with cyclophosphamide for treatment against tumors expressing oncogenic Kras and lacking Trp53) were used. The antitumor response was triggered by direct drug actions on tumor cells, relied on innate immune sensing through toll-like receptor 4 signaling, and ultimately depended on CD8(+) T cell antitumor immunity. Furthermore, instigating tumor infiltration by T cells sensitized tumors to checkpoint inhibition and controlled cancer durably. These findings indicate that the proportion of cancers responding to checkpoint therapy can be feasibly and substantially expanded by combining checkpoint blockade with immunogenic drugs. PMID- 26872702 TI - The policy and politics of the 2015 long-term care reform in the Netherlands. AB - As of 2015 a major reform in LTC is taking place in the Netherlands. An important objective of the reform is to reign in expenditure growth to safeguard the fiscal sustainability of LTC. Other objectives are to improve the quality of LTC by making it more client-tailored. The reform consists of four interrelated pillars: a normative reorientation, a shift from residential to non-residential care, decentralization of non-residential care and expenditure cuts. The article gives a brief overview of these pillars and their underlying assumptions. Furthermore, attention is paid to the political decision-making process and the politics of implementation and evaluation. Perceptions of the effects of the reform so far widely differ: positive views alternate with critical views. Though the reform is radical in various aspects, LTC care will remain a largely publicly funded provision. A statutory health insurance scheme will remain in place to cover residential care. The role of municipalities in publicly funded non-residential care is significantly upgraded. The final section contains a few policy lessons. PMID- 26872699 TI - Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells. AB - Normal repair of skeletal muscle requires local expansion of a special population of Foxp3(+)CD4(+) regulatory T (Treg) cells. Such cells failed to accumulate in acutely injured muscle of old mice, known to undergo ineffectual repair. This defect reflected reduced recruitment of Treg cells to injured muscle, as well as less proliferation and retention therein. Interleukin-33 (IL-33) regulated muscle Treg cell homeostasis in young mice, and its administration to old mice ameliorated their deficits in Treg cell accumulation and muscle regeneration. The major IL-33-expressing cells in skeletal muscle displayed a constellation of markers diagnostic of fibro/adipogenic progenitor cells and were often associated with neural structures, including nerve fibers, nerve bundles, and muscle spindles, which are stretch-sensitive mechanoreceptors important for proprioception. IL-33(+) cells were more frequent after muscle injury and were reduced in old mice. IL-33 is well situated to relay signals between the nervous and immune systems within the muscle context. PMID- 26872704 TI - Realizing a Vision and Moving Forward. PMID- 26872705 TI - Noteworthy Literature in Cardiac Surgery 2015. AB - In 2015, the cardiac literature has pushed for change in cardiac practice. The areas are evolving quickly based on new technology, ranging from percutaneous valves in the aortic position to mechanical support. The new devices in both these fields are changing the way patients are cared for very quickly. Another topic evolving is temperature management in aortic arch cases. This field is being pushed more by the threat of endovascular technology creeping into the arch than technology directly causing change in care. But that threat is real and inevitable. Finally, the discussion about optimal conduits is unending in coronary bypass grafting. A new algorithm has been proposed for utilization of more arterial grafts; however, there remains trepidation in changing from more vein grafts. Furthermore, those pushing for more arterial grafting seem to be black and white about these approaches rather than using what is best for the patient. These topics, among others, have made the literature from cardiac surgery in 2015 worth reading. PMID- 26872703 TI - Effects of a Web-Based Intervention for Stress Reduction in Primary Care: A Cluster Randomized Controlled Trial. AB - BACKGROUND: Preliminary findings suggest that Web-based interventions may be effective in achieving significant stress reduction. To date, there are no findings available for primary care patients. This is the first study that investigates a Web-based intervention for stress reduction in primary care. OBJECTIVE: The aim was to examine the short-term effectiveness of a fully automated Web-based coaching program regarding stress reduction in a primary care setting. METHODS: The study was an unblinded cluster randomized trial with an observation period of 12 weeks. Individuals recruited by general practitioners randomized to the intervention group participated in a Web-based coaching program based on education, motivation, exercise guidance, daily text message reminders, and weekly feedback through the Internet. All components of the program were fully automated. Participants in the control group received usual care and advice from their practitioner without the Web-based coaching program. The main outcome was change in the Perceived Stress Questionnaire (PSQ) over 12 weeks. RESULTS: A total of 93 participants (40 in intervention group, 53 in control group) were recruited into the study. For 25 participants from the intervention group and 49 participants from the control group, PSQ scores at baseline and 12 weeks were available. In the intention-to-treat analysis, the PSQ score decreased by mean 8.2 (SD 12.7) in the intervention group and by mean 12.6 (SD 14.7) in the control group. There was no significant difference identified between the groups (mean difference -4.5, 95% CI -10.2 to 1.3, P=.13). CONCLUSIONS: This trial could not show that the tested Web-based intervention was effective for reducing stress compared to usual care. The limited statistical power and the high dropout rate may have reduced the study's ability to detect significant differences between the groups. Further randomized controlled trials are needed with larger populations to investigate the long-term outcome as well as the contents of usual primary care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00003067; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?=DRKS00003067 (Archived by WebCite at http://www.webcitation.org/6eXk0PXmO). PMID- 26872708 TI - Corrigendum. PMID- 26872706 TI - Cardiopulmonary Bypass Without Heparin. AB - Due to familiarity, short half-life, ease of monitoring, and the availability of a reversal agent, heparin remains the anticoagulant of choice for cardiac operations requiring cardiopulmonary bypass (CPB). However, occasionally patients require CPB but should not receive heparin, most often because of acute or subacute heparin-induced thrombocytopenia (HIT). In these cases, if it is not feasible to wait for the disappearance of HIT antibodies, an alternative anticoagulant must be selected. A number of non-heparin anticoagulant options have been explored. However, current recommendations suggest the use of a direct thrombin inhibitor such as bivalirudin. This review describes the use of heparin alternatives for the conduct of CPB with a focus on the direct thrombin inhibitors. PMID- 26872709 TI - The Effect of Laser Fiber Cleave Technique and Lithotripsy Time on Power Output. AB - PURPOSE: Various cleave techniques have recently been shown to significantly impact initial laser fiber power output during holmium laser lithotripsy. The impact of cleave technique on long-term power output has not been well characterized. The purpose of this study was to determine the effect of laser cleave technique on power output over time. MATERIALS AND METHODS: In this randomized single-blinded study, five cleave techniques were tested on two holmium laser fiber diameters (200, 365 MUm) over 15 minutes of laser lithotripsy with calcium oxalate monohydrate stones. Comparisons between cleave techniques and fiber diameters were performed using independent samples Mann-Whitney U, Kruskal-Wallis, and homogeneity of variance tests with a significance of p < 0.05. RESULTS: The 365-MUm fiber was more durable and less affected by burnback degradation than the 200-MUm fiber (p < 0.05). While initial power output varied between cleave techniques, all significance disappeared by 3 minutes. Power output decreased rapidly by a mean of 0.62 W over 4 minutes (p < 0.05), following which there was no significant change. CONCLUSION: These findings confirm that initial laser fiber power output is significantly influenced by cleave technique, and the ceramic scissor is the optimal tool for cleaving between procedures. However, because of rapid fiber tip degradation and power loss, this study argues against routine cleaving to improve procedural efficiency in lengthy ureteroscopy cases. PMID- 26872711 TI - Editorial: On the Issue Celebrating the Centennial of the Johns Hopkins Bloomberg School of Public Health. PMID- 26872712 TI - The George W. Comstock Center for Public Health Research and Prevention: A Century of Collaboration, Innovation, and Translation. AB - The Johns Hopkins Bloomberg School of Public Health has been engaged in public health research and practice in Washington County, Maryland, nearly since its inception a century ago. In 2005, the center housing this work was renamed the George W. Comstock Center for Public Health Research and Prevention to honor its pioneering leader. Principles that guided innovation and translation well in the past included: research synergies and opportunities for translation realized through longstanding connection with the community; integration of training with public health research; lifelong learning, mentorship, and teamwork; and efficiency through economies of scale. These principles are useful to consider as we face the challenges of improving the health of the population over the next 100 years. PMID- 26872713 TI - Post-traumatic Stress Disorder After Sexual Abuse in Adolescent Girls. AB - The sexual assault of girls and women in this country is estimated at approximately 20%. The development of post-traumatic stress disorder (PTSD) after sexual abuse and assault is one of the potential lingering aftereffects. In this article we describe PTSD after sexual abuse and its effect on presenting complaints, such as sexually transmitted infections, contraception, and chronic pain, for the pediatric and adolescent gynecology (PAG) clinician. Treatment approaches, including the use of antidepressants and anxiolytics, as well as evidenced-based psychotherapies, are highlighted. In addition, this article will assist the PAG clinician in identifying trauma-related concerns during clinic visits and will cover specific screening tools to aid in identification of PTSD. A better understanding of PTSD after sexual abuse will allow PAG providers to deliver better care to their patients. PMID- 26872710 TI - Beyond the Intensive Care Unit (ICU): Countywide Impact of Universal ICU Staphylococcus aureus Decolonization. AB - A recent trial showed that universal decolonization in adult intensive care units (ICUs) resulted in greater reductions in all bloodstream infections and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) than either targeted decolonization or screening and isolation. Since regional health-care facilities are highly interconnected through patient-sharing, focusing on individual ICUs may miss the broader impact of decolonization. Using our Regional Healthcare Ecosystem Analyst simulation model of all health-care facilities in Orange County, California, we evaluated the impact of chlorhexidine baths and mupirocin on all ICU admissions when universal decolonization was implemented for 25%, 50%, 75%, and 100% of ICU beds countywide (compared with screening and contact precautions). Direct benefits were substantial in ICUs implementing decolonization (a median 60% relative reduction in MRSA prevalence). When 100% of countywide ICU beds were decolonized, there were spillover effects in general wards, long-term acute-care facilities, and nursing homes resulting in median 8.0%, 3.0%, and 1.9% relative MRSA reductions at 1 year, respectively. MRSA prevalence decreased by a relative 3.2% countywide, with similar effects for methicillin-susceptible S. aureus. We showed that a large proportion of decolonization's benefits are missed when accounting only for ICU impact. Approximately 70% of the countywide cases of MRSA carriage averted after 1 year of universal ICU decolonization were outside the ICU. PMID- 26872714 TI - Louisiana and Mississippi Family Physicians' Contraception Counseling for Adolescents with a Focus on Intrauterine Contraception. AB - STUDY OBJECTIVE: The adolescent pregnancy rate in Louisiana (LA) and Mississippi (MS) is one of the highest in the United States. One approach to decrease that rate is to increase contraceptive use. We sought to characterize LA and MS family physicians' (FPs) contraception counseling for adolescents with a focus on the intrauterine contraceptive device (IUD). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Online survey of resident and practicing physician members of the LA and MS Academy of FPs. RESULTS: Three hundred ninety-eight of 1616 invited FPs responded; 244 were included in our analysis. When counseling adolescents about contraception, respondents "frequently discussed" oral contraceptives and condoms 87.5% (210/240) and 83.8% (202/241) of the time, respectively. Newer and more highly effective contraceptives such as the ring, patch, IUD, and implant were "frequently discussed" only 34.6% (82/237)-39.3% (92/234) of the time. In the previous 6 months, 56% (136/243) of respondents ever discussed an IUD with an adolescent. Respondents were more likely to have discussed IUDs if they learned IUD insertion during residency, had on-site access to IUD inserters, believed they were competent and/or comfortable with IUD counseling. In 5 clinical scenarios asking whether the respondent would recommend an IUD to a 17- or a 27-year-old patient (in all scenarios patients were eligible for an IUD), respondents were restrictive overall and significantly fewer would recommend an IUD for the adolescent. CONCLUSION: Our results suggest that there are missed opportunities for full-scope contraception counseling by LA and MS FPs. When these FPs counsel adolescents about contraception they less frequently discuss newer methods and more highly effective methods. Additionally many LA and MS FPs use overly restrictive eligibility criteria when considering IUDs. PMID- 26872715 TI - Competition between fast- and slow-diffusing species in non-homogeneous environments. AB - We study an individual-based model in which two spatially distributed species, characterized by different diffusivities, compete for resources. We consider three different ecological settings. In the first, diffusing faster has a cost in terms of reproduction rate. In the second case, resources are not uniformly distributed in space. In the third case, the two species are transported by a fluid flow. In all these cases, at varying the parameters, we observe a transition from a regime in which diffusing faster confers an effective selective advantage to one in which it constitutes a disadvantage. We analytically estimate the magnitude of this advantage (or disadvantage) and test it by measuring fixation probabilities in simulations of the individual-based model. Our results provide a framework to quantify evolutionary pressure for increased or decreased dispersal in a given environment. PMID- 26872716 TI - [General concepts of epigenetics: Projections in paediatrics]. AB - Current evidence supports the notion that alterations in intrauterine growth and during the first years of life have a substantial effect on the risk for the development of chronic disease, which in some cases is even higher than those due to genetic factors. The persistence and reproducibility of the phenotypes associated with altered early development suggest the participation of mechanisms that would record environmental cues, generating a cellular reprogramming (i.e., epigenetic mechanisms). This review is an introduction to a series of five articles focused on the participation of epigenetic mechanisms in the development of highly prevalent chronic diseases (i.e., cardiovascular, metabolic, asthma/allergies and cancer) and their origins in the foetal and neonatal period. This series of articles aims to show the state of the art in this research area and present the upcoming clues and challenges, in which paediatricians have a prominent role, developing strategies for the prevention, early detection and follow-up. PMID- 26872717 TI - Contraception in Japan: Current trends. AB - OBJECTIVES: High proportion of Japanese uses condoms; lower proportion uses oral contraceptive pills (OCPs). We examined the longitudinal patterns for contraceptive usage in Japan and evaluated differences before and after OCP government approval. STUDY DESIGN: We accessed nationally representative survey data for women aged 16-49years from 1950 to 2014. RESULTS: Usage of condoms and OCP was 83.4% and 3.0%, respectively in 2014. OCP use before (1.21%) and after (1.97%) government approval did not differ significantly (p=.58). CONCLUSIONS: The prevalence of OCP usage remains low in Japan. A wide gap in use between Japan and other developed countries exists. IMPLICATIONS: Through a wide gap in OCP use between Japan and other countries, we revealed how choices of contraceptive methods and their benefits could be openly available for women of reproductive age, and how health care professionals disseminate appropriate knowledge about contraception for women in need. PMID- 26872718 TI - Cost of providing injectable contraceptives through a community-based social marketing program in Tigray, Ethiopia. AB - OBJECTIVE: To provide a cost analysis of an injectable contraceptive program combining community-based distribution and social marketing in Tigray, Ethiopia. METHODS: We conducted a cost analysis, modeling the costs and programmatic outcomes of the program's initial implementation in 3 districts of Tigray, Ethiopia. Costs were estimated from a review of program expense records, invoices, and interviews with health workers. Programmatic outcomes include number of injections and couple-year of protection (CYP) provided. We performed a sensitivity analysis on the average number of injections provided per month by community health workers (CHWs), the cost of the commodity, and the number of CHWs trained. RESULTS: The average programmatic CYP was US $17.91 for all districts with a substantial range from US $15.48-38.09 per CYP across districts. Direct service cost was estimated at US $2.96 per CYP. The cost per CYP was slightly sensitive to the commodity cost of the injectable contraceptives and the number of CHWs. The capacity of each CHW, measured by the number of injections sold, was a key input that drove the cost per CYP of this model. CONCLUSION: With a direct service cost of US $2.96 per CYP, this study demonstrates the potential cost of community-based social marketing programs of injectable contraceptives. The findings suggest that the cost of social marketing of contraceptives in rural communities is comparable to other delivery mechanisms with regards to CYP, but further research is needed to determine the full impact and cost-effectiveness for women and communities beyond what is measured in CYP. PMID- 26872719 TI - "If I know I am on the pill and I get pregnant, it's an act of God": women's views on fatalism, agency and pregnancy. AB - OBJECTIVES: Fatalism is the idea that outside forces have control over events. Pregnancy and pregnancy prevention play a prominent role in many women's lives, and we sought to understand if and how fatalism informed their thinking about these issues. STUDY DESIGN: We conducted in-depth interviews with 52 unmarried women between the ages of 18 and 30. We used NVivo to analyze the transcripts. The current analysis focuses on the ways that women discussed fatalism and pregnancy both in response to a direct question and as it came up spontaneously. RESULTS: The majority of respondents expressed a mix of fatalistic and non fatalistic views about pregnancy. Many related that "fate," "destiny" and/or God play a role in pregnancy, but most also asserted that pregnancy risk could be substantially reduced, most commonly by using contraception. Fatalism sometimes served a positive function, for example as a mechanism to deal with an unintended pregnancy. Having a fatalistic outlook did not preclude contraceptive use. Rather, some women using highly effective methods related that if they were to become pregnant, they would interpret it as a sign that the pregnancy was "meant to happen." Finally some women related that there was no guarantee a woman could get pregnant when she wanted to, suggesting that some degree of fatalism may be inevitable when it comes to pregnancy. CONCLUSIONS: Fatalism and agency should not be viewed as opposing outlooks when it comes to pregnancy and pregnancy prevention; having fatalistic views about pregnancy does not preclude contraceptive use. IMPLICATIONS: Given that women do not have total control over attainment of a wanted pregnancy or even prevention of pregnancy, some amount of fatalism about fertility is a logical and pragmatic response. Both research and clinical practice need to recognize that fatalism and contraceptive use are often not in conflict. PMID- 26872720 TI - A Phase III, single-arm study of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5mg) in postmenarcheal adolescents. AB - OBJECTIVE: To assess the safety profile of the low-dose levonorgestrel intrauterine system (LNG-IUS) total content 13.5mg (average approximate release rate 8MUg/24h over the first year; LNG-IUS 8; Jaydess(r)) in adolescents. STUDY DESIGN: In a Phase III study in 36 European centers, 304 healthy nulliparous or parous postmenarcheal adolescents (12-17years) received LNG-IUS 8 for 12months. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included: serious TEAEs, adverse events of special interest, overall user satisfaction, discontinuation rate at 12months, and Pearl Index. RESULTS: LNG-IUS 8 placement was successful in 303/304 participants (99.7%). Overall, 82.6% of participants reported TEAEs, and serious TEAEs and serious study drug-related TEAEs were reported by 7.6% and 1.0% of participants, respectively. No cases of pelvic inflammatory disease, ectopic pregnancy, or uterine perforation were reported. No pregnancies were reported during the 12 month study. At Month 12/study end, the overall user satisfaction rate was 83.9%. Overall, 51 participants (16.8%) prematurely discontinued the study before 12months; 13.8% of participants discontinued owing to TEAEs. CONCLUSIONS: No new or unexpected safety events were associated with the low-dose LNG-IUS 8. The safety profile of LNG-IUS 8 in adolescents was consistent with that previously reported in adults. The high overall user-satisfaction rate at study end and the low discontinuation rate over 12months demonstrate that LNG-IUS 8 is a highly acceptable contraceptive method among adolescents. IMPLICATIONS: This study is the first to assess the low-dose levonorgestrel intrauterine system LNG-IUS 8 (average approximate release rate 8MUg/24h over the first year and total content 13.5mg) specifically in females<18years of age and confirms the safety and efficacy of LNG-IUS 8 in an adolescent population. PMID- 26872722 TI - Fluoxetine-induced toxicity results in human placental glutathione S-transferase pi (GST-pi) dysfunction. AB - CONTEXT: The antidepressant drug fluoxetine (FLU) is considered in the group of selective serotonine re-uptake inhibitors. Its distribution in brain and binding to human brain glutathione S-transferase-pi (GST-pi) have been shown. FLU can cross blood brain barrier and placenta, accumulate in fetus and may cause congenital malformations. OBJECTIVE: To elucidate the interaction of placental GST-pi with FLU. MATERIALS AND METHODS: First, concentration-dependent inhibition of human placental GST-pi was evaluated by using different FLU concentrations and then 0.3125, 0.625, 1.25, 2.5 and 5 mM FLU concentrations were chosen and tested while keeping GSH concentration constant and 1-chloro-2,4-dinitrobenzene (CDNB) concentration varied and vice versa. The data were evaluated with different kinetic models and Statistica 9.00 for Windows. RESULTS: The Vm, at variable [CDNB] (142 +/- 16 U/mg protein) was 3 times higher than the Vm obtained at variable [GSH] (49 +/- 4 U/mg protein). On the other hand, the Km for CDNB was ~10 times higher than the Km for GSH (1.99 +/- 0.36 mM versus 0.21 +/- 0.06 mM). The IC50 value for FLU was 8.6 mM. Both at constant [CDNB] and variable [GSH] and at constant [GSH] and variable [CDNB] the inhibition types were competitive with the Ki values of 5.62 +/- 4.37 and 8.09 +/- 1.27 mM, respectively. CONCLUSION: Although the Ki values obtained for FLU in vitro are high, due to their uneven distribution, long elimination time and inhibitory behavior on detoxification systems, it may cause defects in adults but these effects may be much more severe in fetus and result in congenital malformations. PMID- 26872721 TI - The effect of enriched chicory inulin on liver enzymes, calcium homeostasis and hematological parameters in patients with type 2 diabetes mellitus: A randomized placebo-controlled trial. AB - BACKGROUNDS AND AIMS: Type 2 diabetic mellitus (T2DM) as one of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of enriched chicory inulin supplementation on liver enzymes, serum calcium and phosphorous concentrations and hematological parameters in patients with T2DM. METHODS: Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of chicory and subjects in control group received a placebo for two months. Anthropometric variables, glucose homeostasis, hematological parameters and metabolic indices including serum alanine aminotransfersae (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), calcium and phosphorous as well as creatinine concentrations, glomerular filtration rate (GFR) and blood pressure were assessed at the beginning and end of the trial. RESULTS: Significant reductions in fasting serum glucose (FSG), Hb A1C, AST and ALP concentrations were observed in chicory-treated group. Systolic and diastolic blood pressures were also reduced in chicory-treated group. Serum calcium significantly increased after chicory supplementation but no change in placebo treated group has been occurred (P=0.014). Supplementation with enriched chicory for two months significantly reduced hematocrit and mean corpuscular volume (MCV) values (P<0.05). Changes in serum insulin, creatinine and GFR were not significant. CONCLUSION: The present study showed beneficial effects of oligofructose-enriched chicory on the improvement of the glucose and calcium homeostasis, liver function tests, blood pressure and reduction in hematologic risk factors of diabetes in female patients with T2DM. Further studies in both genders are needed to generalize these findings to total population. PMID- 26872723 TI - Reprogramming carcinoma associated fibroblasts by AC1MMYR2 impedes tumor metastasis and improves chemotherapy efficacy. AB - Carcinoma associated fibroblasts (CAFs) produce a nutrient-rich microenvironment to fuel tumor progression and metastasis. Reactive oxygen species (ROS) levels and the inflammation pathway co-operate to transform CAFs. Therefore, elucidating the mechanism mediating the activity of CAFs might identify novel therapies. Abnormal miR-21 expression was reported to be involved in the conversion of resident fibroblasts to CAFs, yet the factor that drives transformation was poorly understood. Here, we reported that high miR-21 expression was strongly associated with lymph node metastasis in breast cancer, and the activation of the miR-21/NF-kB was required for the metastatic promoting effect of CAFs. AC1MMYR2, a small molecule inhibitor of miR-21, attenuated NF-kB activity by directly targeting VHL, thereby blocking the co-precipitation of NF-kB and beta-catenin and nuclear translocation. Taxol failed to constrain the aggressive behavior of cancer cells stimulated by CAFs, whereas AC1MMYR2 plus taxol significantly suppressed tumor migration and invasion ability. Remodeling and depolarization of F-actin, decreased levels of beta-catenin and vimentin, and increased E-cadherin were also detected in the combination therapy. Furthermore, reduced levels of FAP alpha and alpha-SMA were observed, suggesting that AC1MMYR2 was competent to reprogram CAFs via the NF-kB/miR-21/VHL axis. Strikingly, a significant reduction of tumor growth and lung metastasis was observed in the combination treated mice. Taken together, our findings identified miR-21 as a critical mediator of metastasis in breast cancer through the tumor environment. AC1MMYR2 may be translated into the clinic and developed as a more personalized and effective neoadjuvant treatment for patients to reduce metastasis and improve the chemotherapy response. PMID- 26872724 TI - Reciprocal activation between MMP-8 and TGF-beta1 stimulates EMT and malignant progression of hepatocellular carcinoma. AB - The efficiency of surgery in hepatocellular carcinoma (HCC) is limited due to metastasis and recurrence, but the molecular mechanisms are unclear. Here, we show that MMP-8 and TGF-beta1 accumulate in highly invasive HCC cell lines and invasive HCC patient tissues. Upregulation of MMP-8 and TGF-beta1 correlated with changes in cellular epithelial-mesenchymal transition (EMT) phenotypes and HCC migration and invasion. The expression of TGF-beta1 was markedly restored by MMP 8 overexpression in TGF-beta1-depleted HCC cells mainly via the activation of PI3K/Akt/Rac1 pathway. Similarly, the expression of MMP-8 was restored by TGF beta1 treatment in MMP-8-depleted HCC cells mainly through the activation of the same PI3K/Akt/Rac1 pathway. MMP-8 expression was significantly related to TGF beta1 expression in HCC patient tissues, and high expression of MMP-8 or TGF beta1 was significantly associated with TNM stage and HCC metastasis. Specifically, patients with high co-expression of MMP-8 and TGF-beta1 had a shorter time-to-recurrence than those with low co-expression. Therefore, the reciprocal positive interplay between MMP-8 and TGF-beta1 contributes to HCC invasion and metastasis by inducing EMT mainly through the PI3K/Akt/Rac1 pathway. PMID- 26872725 TI - The histone demethylase LSD1 is a novel oncogene and therapeutic target in oral cancer. AB - The histone demethylase LSD1 functions as a key pro-oncogene and attractive therapeutic target in human cancer. Here we sought to interrogate the oncogenic roles of LSD1 in OSCC tumorigenesis and therapeutic intervention by integrating chemical-induced OSCC model, genetic and pharmacological loss-of-function approaches. Our data revealed that aberrant LSD1 overexpression in OSCC was significantly associated with tumor aggressiveness and shorter overall survival. Increased abundance of LSD1 was detected along with disease progression in DMBA- or 4NQO-induced OSCC animal models. LSD1 depletion via siRNA-mediated knockdown in OSCC cells resulted in impaired cell proliferation, migration/invasion, tumorsphere formation and reduced xenograft growth while inducing cell apoptosis and enhancing chemosensitivity to 5-FU. Moreover, treatments of LSD1 chemical inhibitors (pargyline and tranylcypromine) induced its protein reduction probably via enhanced protein degradation and produced similar phenotypic changes resembling LSD1 silencing in OSCC cells. Pharmacological inhibition of LSD1 by intraperitoneal delivery of these inhibitors resulted in impaired xenograft overgrowth. Taken together, our data reveal the tumorigenic roles of LSD1 and identified LSD1 as a novel biomarker with diagnostic and prognostic significance, and also establish that targeting LSD1 by chemical inhibitors is a viable therapeutic strategy against OSCC. PMID- 26872726 TI - Psychometric study of the European Portuguese version of the PedsQL 3.0 Cancer Module. AB - BACKGROUND: Health-related quality of life (HRQoL) is an important outcome to assess the impact of cancer. This article examines the psychometric properties of the European Portuguese self-report version of the Pediatric Quality of Life InventoryTM Cancer Module (PedsQLTM 3.0 Cancer Module) in children and adolescents with cancer. METHODS: The participants, 332 children/adolescents diagnosed with cancer (8-18 years old), completed measures to assess HRQoL (PedsQLTM 3.0 Cancer Module and DISABKIDS Chronic Generic Measure; DCGM-12) and anxiety (Revised Children's Manifest Anxiety Scale - second edition; RCMAS-2). A subsample (n = 52) completed the PedsQLTM 3.0 Cancer Module a second time following one-week. The pediatric oncologists completed the Intensity of Treatment Rating Scale 3.0 (ITR 3.0). RESULTS: For the whole sample, the PedsQLTM 3.0 Cancer Module demonstrated good item discrimination (rs = .30 to .54). The confirmatory factor analysis testing the presence of eight first-order factors loading significantly in a second-order factor revealed an acceptable fit (CFI = .91; RMSEA = .05). The correlation of PedsQLTM 3.0 Cancer Module with DCGM-12 (rs = .17 to .58), and with RCMAS-2 (rs = -.16 to-.51) attested convergent validity. This inventory demonstrated minimally acceptable to very good internal consistency (alphas = .65 to .87) and temporal stability (ICCs = .61 to .81). CONCLUSIONS: These findings demonstrate that the European Portuguese self-report version of the PedsQLTM 3.0 Cancer Module is a valid and reliable instrument for assessing HRQoL in pediatric cancer. PMID- 26872727 TI - Organic Cation Transporter 1 (OCT1) mRNA expression in hepatocellular carcinoma as a biomarker for sorafenib treatment. AB - BACKGROUND: The polyspecific organ cation transporter 1 (OCT1) is one of the most important active influx pumps for drugs like the kinase inhibitor sorafenib. The aim of this retrospective study was the definition of the role of intratumoral OCT1 mRNA expression in hepatocellular carcinoma (HCC) as a biomarker in systemic treatment with sorafenib. METHODS: OCT1 mRNA expression levels were determined in biopsies from 60 primary human HCC by real time PCR. The data was retrospectively correlated with clinical parameters. RESULTS: Intratumoral OCT1 mRNA expression is a significant positive prognostic factor for patients treated with sorafenib according to Cox regression analysis (HR 0.653, 95%-CI 0.430-0.992; p = 0.046). Under treatment with sorafenib, a survival benefit could be shown using the lower quartile of intratumoral OCT1 expression as a cut-off. Macrovascular invasion (MVI) was slightly more frequent in patients with low OCT1 mRNA expression (p = 0.037). Treatment-induced AFP response was not associated with intratumoral OCT1 mRNA expression levels (p = 0.633). CONCLUSIONS: This study indicates a promising role for intratumoral OCT1 mRNA expression as a prognostic biomarker in therapeutic algorithms in HCC. Further prospective studies are warranted on this topic. PMID- 26872728 TI - Respiratory Effects on Fontan Circulation During Rest and Exercise Using Real Time Cardiac Magnetic Resonance Imaging. AB - BACKGROUND: It is known that respiration modulates cavopulmonary flows, but little data compare mean flows under breath-holding and free-breathing conditions to isolate the respiratory effects and effects of exercise on the respiratory modulation. METHODS: Real-time phase-contrast magnetic resonance combined with a novel method to track respiration on the same image acquisition was used to investigate respiratory effects on Fontan caval and aortic flows under breath holding, free-breathing, and exercise conditions. Respiratory phasicity indices that were based on beat-averaged flow were used to quantify the respiratory effect. RESULTS: Flow during inspiration was substantially higher than expiration under the free-breathing and exercise conditions for both inferior vena cava (inspiration/expiration: 1.6 +/- 0.5 and 1.8 +/- 0.5, respectively) and superior vena cava (inspiration/expiration: 1.9 +/- 0.6 and 2.6 +/- 2.0, respectively). Changes from rest to exercise in the respiratory phasicity index for these vessels further showed the impact of respiration. Total systemic venous flow showed no significant statistical difference between the breath-holding and free breathing conditions. In addition, no substantial difference was found between the descending aorta and inferior vena cava mean flows under either resting or exercise conditions. CONCLUSIONS: This study demonstrated that inferior vena cava and superior vena cava flow time variance is dominated by respiratory effects, which can be detected by the respiratory phasicity index. However, the minimal respiration influence on net flow validates the routine use of breath-holding techniques to measure mean flows in Fontan patients. Moreover, the mean flows in the inferior vena cava and descending aorta are interchangeable. PMID- 26872730 TI - The Impact of Thoracoscopic Surgery on Payment and Health Care Utilization After Lung Resection. AB - BACKGROUND: Lung resection by video-assisted thoracoscopic surgery (VATS) is associated with multiple clinical benefits compared with resection by thoracotomy (OPEN). Less is known about reimbursements, costs, and resource use with each approach. This study used a commercial insurance claims database to examine differences between VATS and OPEN lung resections in payment, health care utilization, and estimated days off work for health care visits. METHODS: All adult inpatient discharges for patients undergoing VATS or OPEN lung resection in 2010 were identified from the Truven MarketScan Database (Ann Arbor, MI). RESULTS: A total of 2,611 patients underwent lobectomy (VATS, 270; OPEN, 669) or wedge resection (VATS, 1,332; OPEN, 340). After adjustment, OPEN lobectomies had a longer length of stay (mean difference, 1.79 days) and higher payment to hospitals (mean difference, $3,497) and physicians (mean difference, $433) compared with VATS. Similar findings were noted after wedge resections. OPEN lobectomies had 1.28-times and 1.14-times more health care utilization days within 90 days and 365 days, respectively, after the operation compared with VATS, translating into increased expenditures of $3,260 at 90 days and $822 at 365 days for OPEN procedures. No significant differences in utilization were noted between OPEN and VATS wedge resections, except for fewer outpatient visits within 90 days in the OPEN group. CONCLUSIONS: Compared with an OPEN approach, lobectomy and wedge resection by VATS were associated with lower hospital and physician payments. In addition, lobectomy by VATS was associated with less health care utilization in the early postoperative period and during the first year after the operation. These payment and utilization reductions are important in an era of value-based purchasing in health care. PMID- 26872729 TI - Rifampin for Surgically Treated Staphylococcal Infective Endocarditis: A Propensity Score-Adjusted Cohort Study. AB - BACKGROUND: Rifampin is recommended as adjunctive treatment for staphylococcal prosthetic valve endocarditis (PVE). It is unclear whether this should hold for surgically treated patients. The purpose of this study was to examine whether adjunctive rifampin treatment in addition to cell wall active antimicrobial agents in patients with surgically treated staphylococcal infective endocarditis (IE) results in better outcomes. METHODS: Patients operated on for staphylococcal IE from April 1, 2008, to July 1, 2014, were identified from our institution's IE registry. Rifampin treatment was defined as 3 or more days of rifampin postoperatively. Cox proportional hazards regression was used to compare a composite outcome of death or reoperation for IE relapse, between patients treated and not treated with rifampin, adjusted for propensity to be treated with rifampin, methicillin resistance, all-purpose refined diagnosis related group (APR-DRG) severity score, and APR-DRG mortality risk. RESULTS: In all, 273 patients were identified. The mean age was 56 years, 66% were male, 50% had PVE, 60% had S. aureus or S. lugdunensis infection, 89% had left side involvement, and 57% had invasive disease. Fifty-one (27%) received 3 or more days of rifampin postoperatively. Ninety-two patients died or underwent reoperation for IE relapse at a median of 205 days (interquartile range 56 to 718 days). In a multivariable model, patients treated with rifampin had a similar hazard of death or reoperation for IE relapse as those not treated (hazard ratio 0.76, 95% confidence interval 0.44 to 1.32, p value 0.34). The results were robust to varying definitions of rifampin treatment. CONCLUSIONS: Among patients with surgically treated staphylococcal IE there was insufficient evidence to claim a reoperation-free survival benefit from treatment with rifampin. Rifampin should not be used as adjunctive therapy for staphylococcal IE in patients who have undergone surgical procedures for its treatment. PMID- 26872731 TI - Prospective Validation of a Novel Vasoactive-Ventilation-Renal Score as a Predictor of Outcomes After Pediatric Cardiac Surgery. AB - BACKGROUND: We sought to further validate the novel vasoactive-ventilation-renal (VVR) score in a prospective study of a heterogeneous cohort of children undergoing cardiac surgery that includes patients with single-ventricle anatomy and residual mixing lesions. METHODS: We prospectively performed an observational study of all children less than 18 years of age who underwent surgery for congenital heart disease at our center from November 2013 to June 2014. We calculated VVR score as follows: vasoactive-inotrope score + ventilation index + (change in serum creatinine from baseline * 10). Admission, peak, and 48-hour measurements were recorded. Outcomes of interest were prolonged duration of mechanical ventilation and intensive care unit and hospital stays, represented by the upper 25% for all patients. Areas under the receiver-operating characteristic curves (AUC) were determined for all study timepoints and outcome variables. RESULTS: Ninety-two patients were analyzed; their median age was 0.65 (range, 3 days to 17.9 years), and 17 (18%) had single-ventricle anatomy. The VVR measurements outperformed vasoactive-inotrope scores in isolation at all timepoints, with higher AUC values for all outcomes. Of the three timepoints assessed, the 48-hour VVR score most consistently predicted poor outcome, especially with regard to prolonged duration of mechanical ventilation (AUC 0.980) and prolonged intensive care unit stay (AUC 0.919). CONCLUSIONS: In a heterogeneous population of children undergoing cardiac surgery, the 48-hour VVR score was a very strong predictor of outcomes, and outperformed the more traditional vasoactive-inotrope score. The VVR score, therefore, represents a novel and potentially powerful means of predicting clinical outcomes relatively early in the hospital course of these patients. PMID- 26872732 TI - Propensity Score Analysis Comparing Videothoracoscopic Lobectomy With Thoracotomy: A French Nationwide Study. AB - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy has recently become the recommended approach for stage I non-small cell lung cancer. However, these guidelines are not based on any large randomized control trial. Our study used propensity scores and a sensitivity analysis to compare VATS lobectomy with open thoracotomy. METHODS: From 2005 to 2012, 24,811 patients (95.1%) were operated on by open thoracotomy and 1,278 (4.9%) by VATS. The end points were 30 day postoperative death, postoperative complications, hospital stay, overall survival, and disease-free survival. Two propensity scores analyses were performed: matching and inverse probability of treatment weighting, and one sensitivity analysis to unmask potential hidden bias. A subgroup analysis was performed to compare "high-risk" with "low-risk" patients. Results are reported by odds ratios or hazard ratios and their 95% confidence intervals. RESULTS: Postoperative death was not significantly reduced by VATS whatever the analysis. Concerning postoperative complications, VATS significantly decreased the occurrence of atelectasis and pneumopathy with both analysis methods, but there were no differences in the occurrence of other postoperative complications. VATS did not provide a benefit for high-risk patients. The VATS approach decreased the hospital length of stay from 2.4 days (95% confidence interval, -1.7 to -3 days) to -4.68 days (95% confidence interval, -8.5 to 0.9 days). Overall survival and disease-free survival were not influenced by the surgical approach. The sensitivity analysis showed potential biases. CONCLUSIONS: The results must be interpreted carefully because of the differences observed according to the propensity scores method used. A multicenter randomized controlled trial is necessary to limit the biases. PMID- 26872733 TI - High Risk of Prosthetic Valve Endocarditis and Death After Valve Replacement Operations in Dialysis Patients. AB - BACKGROUND: Despite a high burden of dialysis access-related bloodstream infections and an increasing incidence of endocarditis, few data are available addressing the risk of prosthetic valve endocarditis (PVE) in the dialysis population. We sought to assess the risk of PVE and death after valve replacement operations in patients receiving long-term dialysis. METHODS: A matched retrospective cohort study was conducted comprising patients admitted for valve replacement operations at two university hospitals. Patients without dialysis were matched 1:1 with dialysis patients by valve(s) replaced, year of operation, and presence of active endocarditis as the indication for valve replacement. Patient characteristics were compared using chi(2) and t tests. The development of PVE was defined by use of the modified Duke criteria and analyzed with Cox proportional hazards regression. RESULTS: Two hundred seventy-eight patients were included, with 139 in either cohort. The PVE risk per year of follow-up was 0.14 in the dialysis cohort and 0.03 in the nondialysis cohort. Dialysis remained a risk factor (adjusted hazard ratio 5.61 [95% confidence interval, 2.17 to 14.5], p = 0.0004) after age and race were controlled for. The 5-year survival rate was lower after valve replacement operation in the dialysis group (25.4%) than in the nondialysis group (75.9%, p < 0.001). CONCLUSIONS: The risk of PVE and death after valve replacement operations in dialysis patients is substantial and significantly higher than in patients without dialysis. These findings highlight the importance of a careful preoperative risk-benefit assessment and underscore the need to prevent hemodialysis-related bloodstream infections. PMID- 26872734 TI - The Impact of Vascular Complications on Survival of Patients on Venoarterial Extracorporeal Membrane Oxygenation. AB - BACKGROUND: There are various factors that can influence the survival of patients receiving venoarterial extracorporeal membrane oxygenation (VA ECMO). Vascular complications from femoral cannulation are common and are potentially serious. We analyzed the impact of vascular complications on survival of patients receiving VA ECMO. METHODS: Patients supported with VA ECMO by means of femoral cannulation from October 2010 to November 2014 were enrolled in this study. Data were gathered retrospectively by reviewing our institutional database. Patients were separated into two groups depending on the presence of major vascular complications, defined as patients who required surgical intervention. We evaluated predisposing factors for vascular complications and compared survival of patients in each group. RESULTS: There were 84 patients enrolled in the study. The rates of overall ECMO survival and survival to hospital discharge were 60% and 43%, respectively. Major vascular complications requiring surgical intervention were seen in 17 (20%) patients. Ten patients (12%) had compartment syndrome requiring prophylactic fasciotomy, and 10 patients (12%) had bleeding or hematoma requiring surgical exploration. The only significant predisposing factor for vascular complications was the absence of a distal perfusion catheter (odds ratio, 14.8; p = 0.03). The rate of survival to discharge was 18% and 49% in patients with and without vascular complications, respectively (p = 0.02). Vascular complications were an independent factor of significantly worse survival in patients receiving VA ECMO by multivariate analysis (hazard ratio, 2.17; p = 0.02). CONCLUSIONS: Vascular complications negatively affect survival in patients receiving VA ECMO support by means of femoral cannulation. The utilization of a distal perfusion catheter can decrease the incidence of complications. PMID- 26872735 TI - Aortic Valve Replacement With Carpentier-Edwards: Hemodynamic Outcomes for the 19 mm Valve. AB - BACKGROUND: To compare hemodynamic performance and clinical outcomes after aortic valve replacement for aortic stenosis with the 19-mm Carpentier-Edwards pericardial bioprosthesis versus larger valves. METHODS: Between January 1998 and December 2013, 447 consecutive patients underwent aortic valve replacement for aortic stenosis with the Carpentier-Edwards Perimount (n = 61) or Magna bioprostheses (n = 386). Based on the implanted valve size, the patients were classified into three groups: a 19-mm group (n = 54), a 21-mm group (n = 154), and a 23-mm to 27-mm group (n = 239). The in vivo effective orifice area index was measured by transthoracic echocardiography 12 months after operation (n = 331). The mean follow-up time was 4.9 +/- 3.5 (maximum 15.4) years. RESULTS: There were three early deaths (0.7%). At 10 years, overall survival (84.1%) was unaffected by patient-prosthesis mismatch (18.7%, 62 patients), and freedom from structural valve deterioration and endocarditis was 100% and 97.1%, respectively. Although the 19-mm group was significantly older and had a higher incidence of patient-prosthesis mismatch (n = 14, 30.4%), there were no significant differences in early outcomes, overall survival, cardiac-related mortality, or serial reduction of left ventricular mass index in comparison with patients with a larger bioprostheses. Independent risk factors for all-cause mortality were age, male gender, combined coronary artery bypass graft, and low hemoglobin level. CONCLUSION: The Carpentier-Edwards pericardial bioprosthesis appears to be associated with acceptable clinical outcomes and hemodynamic profile. PMID- 26872736 TI - [Mustarde flap lower eyelid reconstruction following lentigo maligna excision]. PMID- 26872738 TI - Health literacy: applying current concepts to improve health services and reduce health inequalities. AB - The concept of 'health literacy' refers to the personal and relational factors that affect a person's ability to acquire, understand and use information about health and health services. For many years, efforts in the development of the concept of health literacy exceeded the development of measurement tools and interventions. Furthermore, the discourse about and development of health literacy in public health and in clinical settings were often substantially different. This paper provides an update about recently developed approaches to measurement that assess health literacy strengths and limitations of individuals and of groups across multiple aspects of health literacy. This advancement in measurement now allows diagnostic and problem-solving approaches to developing responses to identified strengths and limitations. In this paper, we consider how such an approach can be applied across the diverse range of settings in which health literacy has been applied. In particular, we consider some approaches to applying health literacy in the daily practice of health-service providers in many settings, and how new insights and tools--including approaches based on an understanding of diversity of health literacy needs in a target community--can contribute to improvements in practice. Finally, we present a model that attempts to integrate the concept of health literacy with concepts that are often considered to overlap with it. With careful consideration of the distinctions between prevailing concepts, health literacy can be used to complement many fields from individual patient care to community-level development, and from improving compliance to empowering individuals and communities. PMID- 26872737 TI - Re: To screen or not to screen for adolescent idiopathic scoliosis? A review of the literature. PMID- 26872739 TI - Dyspnea, a high-risk symptom in patients suspected of myocardial infarction in the ambulance? A population-based follow-up study. AB - BACKGROUND: Systematic management of patients suffering high-risk symptoms is essential in emergency medical services. Patients with chest pain receive algorithm-based work-up and treatment. Though dyspnea is recognized as an independent predictor of mortality, no generally accepted prehospital treatment algorithm exists and this may affect outcome. The objective of this study was to compare mortality in patients suspected of myocardial infarction (MI) presenting with dyspnea versus chest pain in the ambulance. METHODS: Follow-up study in patients undergoing electrocardiogram-based telemedical triage because of suspected MI in an ambulance in the Central Denmark Region from 1 June 2008 to 1 January 2013. Primary outcome was 30-day mortality. Secondary outcomes were 4 year mortality and mortality rates in subgroups of patients with and without a confirmed MI. Absolute risk differences adjusted for comorbidity, age, systolic blood pressure and heart rate were calculated by a generalized linear regression model. RESULTS: Of 17,398 patients, 12,230 (70%) suffered from chest pain, 1464 (8%) from dyspnea, 3540 (20%) from other symptoms and 164 (1%) from cardiac arrest. Among patients with dyspnea, 30-day mortality was 13% (CI 12-15) and 4 year mortality was 50% (CI 47-54) compared to 2.9% (CI 2.6-3.2) and 20% (CI 19 21) in patients with chest pain. MI was confirmed in 121 (8.3%) patients with dyspnea and in 2319 (19%) with chest pain. Patients with dyspnea and confirmed MI had a 30-day and 4-year mortality of 21 % (CI 15-30) and 60% (CI 50-70) compared to 5.0% (CI 4.2-5.8) and 23% (CI 21-25) in patients with chest pain and confirmed MI. Adjusting for age, comorbidity, systolic blood pressure and heart rate did not change these patterns. CONCLUSION: Patients suspected of MI presenting with dyspnea have significantly higher short- and long-term mortality than patients with chest pain irrespective of a confirmed MI diagnosis. Future studies should examine if supplementary prehospital diagnostics can improve triage, facilitate early therapy and improve outcome in patients presenting with dyspnea. PMID- 26872742 TI - PPARgamma non-covalent antagonists exhibit mutable binding modes with a similar free energy of binding: a case study. AB - The structural and dynamical properties of PPARgamma receptor in a complex with either partial or full agonists have been intensively studied but little is known about the receptor antagonistic conformation. A composition of microsecond accelerated molecular dynamics (aMD) simulation show that like partial agonists a non-covalent PPARgamma full antagonist can bind in different modes of similar population size and free energies of binding. Four different and periodically exchanging ligand conformations are detected and described. The studied antagonist interacts with different receptor substructures and affects both the co-activator and the Cdk5 phosphorylation sites and, presumably, the natural complex with the DNA. However, no significant changes in the conformational states of the activation helix 12, and in particular an antagonist orientation, have been recorded. Finally, our results show also that the aMD approach can be successfully used in recovering the possible binding modes, considering fully the receptor flexibility, and is not dependent on the starting conformation. PMID- 26872741 TI - Towards integration of palliative care in patients with chronic heart failure and chronic obstructive pulmonary disease: a systematic literature review of European guidelines and pathways. AB - BACKGROUND: Despite the positive impact of Palliative Care (PC) on the quality of life for patients and their relatives, the implementation of PC in non-cancer health-care delivery in the EU seems scarcely addressed. The aim of this study is to assess guidelines/pathways for integrated PC in patients with advanced Chronic Heart Failure (CHF) and Chronic Obstructive Pulmonary Disease (COPD) in Europe via a systematic literature review. METHODS: Search results were screened by two reviewers. Eligible studies of adult patients with CHF or COPD published between 01/01/1995 and 31/12/2013 in Europe in 6 languages were included. Nine electronic databases were searched, 6 journals were hand-searched and citation tracking was also performed. For the analysis, a narrative synthesis was employed. RESULTS: The search strategy revealed 26,256 studies without duplicates. From these, 19 studies were included in the review; 17 guidelines and 2 pathways. 18 out of 19 focused on suffering reduction interventions, 13/19 on a holistic approach and 15/19 on discussions of illness prognosis and limitations. The involvement of a PC team was mentioned in 13/19 studies, the assessment of the patients' goals of care in 12/19 and the advance care planning in 11/19. Only 4/19 studies elaborated on aspects such as grief and bereavement care, 7/19 on treatment in the last hours of life and 8/19 on the continuation of goal adjustment. CONCLUSION: The results illustrate that there is a growing awareness for the importance of integrated PC in patients with advanced CHF or COPD. At the same time, however, they signal the need for the development of standardized strategies so that existing barriers are alleviated. PMID- 26872740 TI - Exome sequencing in one family with gastric- and rectal cancer. AB - BACKGROUND: Heritable factors are well known to increase the risk of cancer in families. Known susceptibility genes account for a small proportion of all colorectal cancer cases. The aim of this study was to identify the genetic background in a family suggested to segregate a dominant cancer syndrome with a high risk of rectal- and gastric cancer. We performed whole exome sequencing in three family members, 2 with rectal cancer and 1 with gastric cancer and followed it up in additional family members, other patients and controls. RESULTS: We identified 12 novel non-synonymous single nucleotide variants, which were shared among 5 affected members of this family. The mutations were found in 12 different genes; DZIP1L, PCOLCE2, IGSF10, SUCNR1, OR13C8, EPB41L4B, SEC16A, NOTCH1, TAS2R7, SF3A1, GAL3ST1, and TRIOBP. None of the mutations was suggested as a high penetrant mutation. It was not possible to completely rule out any of the mutations as contributing to disease, although seven were more unlikely than the others. Neither did we rule out the effect of all thousands of intronic, intergenic and synonymous variants shared between the three persons used for exome sequencing. CONCLUSIONS: We propose this family, suggested to segregate dominant disease, could be an example of complex inheritance. PMID- 26872743 TI - Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. AB - BACKGROUND: Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. NEW METHOD: A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50MUm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. RESULTS: Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. COMPARISON WITH EXISTING METHOD(S): Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. CONCLUSIONS: Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments. PMID- 26872744 TI - Use of a size-resolved 1-D resuspension scheme to evaluate resuspended radioactive material associated with mineral dust particles from the ground surface. AB - A size-resolved, one-dimensional resuspension scheme for soil particles from the ground surface is proposed to evaluate the concentration of radioactivity in the atmosphere due to the secondary emission of radioactive material. The particle size distributions of radioactive particles at a sampling point were measured and compared with the results evaluated by the scheme using four different soil textures: sand, loamy sand, sandy loam, and silty loam. For sandy loam and silty loam, the results were in good agreement with the size-resolved atmospheric radioactivity concentrations observed at a school ground in Tsushima District, Namie Town, Fukushima, which was heavily contaminated after the Fukushima Dai ichi Nuclear Power Plant accident in March 2011. Though various assumptions were incorporated into both the scheme and evaluation conditions, this study shows that the proposed scheme can be applied to evaluate secondary emissions caused by aeolian resuspension of radioactive materials associated with mineral dust particles from the ground surface. The results underscore the importance of taking soil texture into account when evaluating the concentrations of resuspended, size-resolved atmospheric radioactivity. PMID- 26872746 TI - Ovarian Pregnancy. PMID- 26872745 TI - Clinical features of organizing pneumonia associated with rheumatoid arthritis. AB - OBJECTIVES: To clarify the clinical features of organizing pneumonia (OP) associated with rheumatoid arthritis (RA) and to determine whether development of OP is related to RA activity. METHODS: A cross-sectional study was conducted, in which medical records of 499 consecutive RA patients who visited our hospital during one month were reviewed. OP was diagnosed by pathological findings by trans-bronchial biopsy or by clinical features (typical computed tomography findings, no causative agents, good response to glucocorticoids, and lack of response to antibiotics). RESULTS: Among 499 patients, OP was found in 19 patients and the estimated prevalence was 1.9-4.8%. No differences in clinical features were noted between the OP and non-OP groups. The mean age of OP development was 57.2 years and the period from the onset of RA to OP ranged from 4 to +34 years. Although 14 patients presented OP after the onset of RA, two developed OP before RA and three developed OP simultaneously with RA. Patients receiving tumor necrosis factor inhibitors also developed OP. RA disease activity just before onset of OP was low in 8 of 14 RA cases. At the onset of OP, only two patients showed exacerbations of arthritis, whereas most patients presented with fever and serum C-reactive protein (CRP) elevations. Glucocorticoids were effective for OP in all patients who received them. Relapse occurred in 4 of 19 cases. CONCLUSIONS: OP develops in approximately 4% of RA patients, which occurs independently from arthritis activity and at any time in RA patients. PMID- 26872747 TI - Not Fade Away. PMID- 26872748 TI - Preparedness for Implementing Change in Neonatal Ocular Prophylaxis Policies. PMID- 26872749 TI - Joint Position Paper on Rural Surgery and Operative Delivery. PMID- 26872750 TI - Pregnancy in Women With Intellectual and Developmental Disabilities. AB - OBJECTIVE: Our objectives were to describe the general fertility rate (GFR) and age-specific fertility rates (ASFRs) of women with intellectual and developmental disabilities (IDD) and the social and health characteristics of those with a singleton live birth, and to compare these to women without IDD. METHODS: In this population-based retrospective cohort study using linked Ontario health and social services administrative data, we identified 18- to 49-year-old women with IDD (N = 21 181) and without IDD (N = 990 776). The GFR and ASFRs (2009) were calculated for both groups and compared using rate ratios (RR) and 95% confidence intervals (CI). Among women with a singleton live birth (N = 423 with, N = 42 439 without IDD), social and health characteristics were compared using Pearson's Chi square tests. RESULTS: The GFR in women with IDD (20.3 per 1000) was lower than that in women without IDD (43.4 per 1000) (RR 0.47; 95% CI 0.43 to 0.51). ASFRs in 18- to 24-year-olds were similar in both groups. Among women with a singleton live birth, those with IDD were younger and had higher rates of poverty, epilepsy, obesity, and mental health issues. They also had high rates of medication use during pregnancy. CONCLUSION: In the largest study of fertility in women with IDD to date, we found that ASFRs are similar in young women with and without IDD. Women with IDD with a singleton live birth experience significant social and health disparities during pregnancy. These findings suggest the need to develop services to support the reproductive health of this vulnerable group. PMID- 26872751 TI - Fetal Outcomes of Prenatally Diagnosed Congenital Diaphragmatic Hernia: Nine Years of Clinical Experience in a Canadian Tertiary Hospital. AB - OBJECTIVE: To summarize the clinical outcome of congenital diaphragmatic hernia (CDH) identified on prenatal ultrasound. METHOD: We reviewed prenatally detected cases of CDH diagnosed between July 2000 and September 2009 at a single tertiary care facility. RESULTS: Ninety-one cases were identified. Sixty-nine cases had complete medical records including karyotype. Of these, 40 were isolated defects and 29 cases had additional congenital or chromosome anomalies. An abnormal karyotype was present in 17.4% overall, affecting 2.5% of cases of isolated CDH (1/40) and 37.9% of cases of non-isolated CDH (11/29). The rate of termination of pregnancy in cases of isolated CDH diagnosed prior to 24 weeks was 33.3% (10/30), and in cases of non-isolated CDH it was 73.9% (17/23). The survival rate of the 44 liveborn infants was 66.7% (24/36) for those with isolated CDH and 37.5% (3/8) for those with non-isolated CDH. The decision to terminate the pregnancy was made in 73.9% of fetuses with prenatally diagnosed karyotype or additional anatomical abnormalities, in contrast to 37.5% of prenatally diagnosed isolated CDH. CONCLUSION: The outcomes of pregnancies that continue after identification of CDH are in keeping with previous reports, with an overall survival rate of 61.4%. The presence of additional anatomical anomalies was the only predictor of mortality among liveborn infants. PMID- 26872752 TI - Maternal Risk Factors and Outcomes of Umbilical Cord Prolapse: A Population-Based Study. AB - OBJECTIVE: Umbilical cord prolapse (UCP) is a rare event believed to be associated with adverse outcomes. The purpose of our study was to use a large administrative database to better identify incidence, predictors, and outcomes of births with UCP. METHODS: We carried out a retrospective cohort study using data from the National Center for Health Statistics- Linked Birth Infant Death and Fetal Death (United States) data files during the years 2003-2005. The incidence, predictors, and outcomes of births with UCP were compared to births with no UCP. Logistic regression analysis was performed to estimate the adjusted effect of UCP on maternal and neonatal outcomes. RESULTS: There were 16 126 cases of UCP among 10 040 416 births, for an incidence of 16.1 cases per 10 000 births. While most cases occurred at term and in women with one or two previous births, early gestational age, grand multiparity, prolonged labour, and malpresentation were the strongest risk factors. UCP was associated with an increased risk of placental abruption, excessive bleeding, Caesarean sections, lower Apgar scores, requiring assisted ventilation, neonatal seizures, hyaline membrane disease, and fetal injuries. Deliveries by Caesarean section were associated with a greater risk of fetal injuries than vaginal delivery (18.5% vs 8.7%; OR 2.6, 95% CI 2.3 to 2.9, P < 0.001). CONCLUSION: Although there are established risk factors, UCP occurs most commonly in low risk women at term. When possible, vaginal delivery is preferred in women with UCP because it appears to be associated with a lower risk of fetal injury. PMID- 26872753 TI - Longitudinal Rates and Risk Factors for Adverse Birth Weight Among First Nations Pregnancies in Alberta. AB - OBJECTIVE: We wished to identify the prevalence, longitudinal trends, and associated risk factors for various birth weight categories by First Nations ethnicity in the province of Alberta. METHODS: We performed a retrospective analysis of administrative data for the years 2000 to 2009 inclusive. Age adjusted prevalence trends for high birth weight (HBW; > 4000g), very HBW (> 4500g), low birth weight (LBW; < 2500g), and very LBW (< 1500g) were compared via average annual percent change analyses. Logistic regression analysis was used to determine risk factors. RESULTS: First Nations ethnicity was a significant independent predictor of HBW (OR 1.82 [95% CI 1.75, 1.89]), very HBW (OR 2.35 [95% CI 2.18, 2.52]), and very LBW (OR 1.35 [95% CI 1.23, 1.48]), but not of LBW (OR 0.98 [95% CI 0.93, 1.03]). However, HBW prevalence decreased and other birth weight categories remained stable over time in First Nations populations. Gestational diabetes and maternal weight >= 91 kg were potentially manageable risk factors for HBW. Potentially manageable risk factors for LBW included pre gestational renal disease, hypertension, and maternal weight <= 45 kg, as well as smoking, illicit drug dependence, and alcohol consumption. CONCLUSION: Although HBW, very HBW, and very LBW remain more common in Alberta First Nations populations than in the general population, their prevalence is not increasing. PMID- 26872754 TI - A Ten-Year Review of Antenatal Complications and Pregnancy Outcomes Among HIV Positive Pregnant Women. AB - OBJECTIVE: To review the incidence of antenatal complications among a cohort of HIV-positive pregnant women over a 10-year period. METHODS: A retrospective review was performed of all HIV-positive pregnant women receiving multidisciplinary prenatal care at an urban tertiary care centre from March 2000 to March 2010. Collected data included the presence of additional infectious or medical conditions, genetic screening information, and the presence or absence of antenatal complications. RESULTS: One hundred and forty-two singleton pregnancies during the study period were identified. Almost 95% of women were taking combination antiretroviral therapy during pregnancy, and greater than 90% had viral loads less than 1000 copies/ml at delivery. The presence of co-infections was low. Forty-one women (29%) had other medical comorbidities. Genetic screening occurred in 104 pregnancies (73%); 4% were abnormal screens. Rates of any hypertension, gestational diabetes, and fetal growth restriction were all low. Thirty-two percent of women were colonized with group B streptococcus. CONCLUSION: This study adds strength to the argument that good outcomes can be achieved for HIV-positive pregnant women with good access to both prenatal and HIV care, and appropriate management. Women with HIV should be optimally cared for in advance of and during pregnancy in order to maximize the likelihood of good pregnancy outcomes. PMID- 26872755 TI - Luteinized Thecomas ("Thecomatosis") with Sclerosing Peritonitis (LTSP): Report of 2 Cases and Review of an Enigmatic Syndrome Associated with a Peritoneal Proliferation of Specialized (vimentin+/keratin+/CD34+) Submesothelial Fibroblasts. AB - OBJECTIVE: To present the clinicopathologic features of two cases of luteinized thecomas with sclerosing peritonitis (LTSP), characterize the cellular proliferation in the sclerosing peritonitis (SP), and review the literature. METHODS: The clinical, laboratory, and imaging data, operative findings, and pathology materials were reviewed and summarized. Samples of the SP were stained with keratin AE1/AE3, vimentin, CD34, calretinin, smooth muscle actin, ER/PR, CD10 and desmin. A literature search was performed to identify cases of LTSP for comparison. RESULTS: A total of 43 cases of LTSP syndrome were identified. Frequent clinical features included ascites (74%), abdominal pain (35%), bowel obstruction (42%), and bilateral masses (84%). We isolated a distinct form of ovarian luteinized thecoma (thecomatosis) and peculiar sclerosing peritonitis (SP). IHC analysis shows a proliferation of specialized (vimentin+/keratin+/CD34+) submesothelial fibroblasts (SMF) with patchy expression of calretinin and hormone receptors. CONCLUSION: LTSP syndrome is a rare entity presenting with abdominal pain, bowel obstruction, ascites, ovarian masses, and SP containing specialized (vimentin+/keratin+/CD34+) SMF. LTSP must be distinguished from abdominal cocoon, isolated SP, Meigs' syndrome, and peritoneal carcinomatosis. The importance of recognizing the diagnosis is stressed, as failure to manage this disease conservatively leads to significant morbidity and mortality. The SP and bowel obstruction may persist for months, even after resection of the tumours, resulting in extended medical therapy. Based on the immunophenotype of the peritoneal lesions, strategies to elucidate 'targeted' pharmacologic agents that could inhibit the proliferation of specialized (vimentin+/keratin+/CD34+) SMF may be of benefit. PMID- 26872756 TI - Outcomes of a Decade of Routine Cervical Screening in a Canadian Adolescent Obstetrics Clinic. AB - OBJECTIVE: New recommendations from the Ontario Cervical Cancer Screening Program indicate that initiation of screening should be delayed to age 21. However, there is sparse evidence pertaining to pregnant adolescents. Our objective was to determine whether early cervical cancer screening in pregnant adolescents confers an advantage over delayed screening in the prevention of cervical carcinoma. METHODS: We conducted a retrospective cohort study of cervical cancer screening in all pregnant adolescents receiving antenatal care through an obstetrics clinic for adolescents between 2000 and 2010. Clinic attendees had an antenatal and/or postpartum Pap smear, with follow-up according to standard recommendations. Results were recorded together with information on regression, persistence, or progression of abnormal cytology, colposcopy referrals, and cervical biopsies. There is a single regional colposcopy clinic. RESULTS: At least one Pap smear result was documented in 365 of the 388 patients. Of these 365 smears, 88 had abnormal cytology, 76 (86.4%) of which were reported as atypical cells of undetermined significance/low-grade squamous intraepithelial lesion, 11 (12.5%) high-grade squamous intraepithelial lesion (HSIL), and one atypical glandular cells (1.1%). Follow-up cytology was available for 78 patients. No patient lost to follow-up had subsequent referrals for colposcopic assessment in the region. Overall, cytologic abnormalities regressed in 75 (96.1%), persisted in two (2.6%), and progressed in one patient (1.3%). Twenty-three patients (of 365) required a total of 68 colposcopy visits and 17 biopsies, but ultimately only three loop electrosurgical excision procedures (LEEPs) and one laser vaporization were performed. Only one LEEP in a 20-year-old demonstrated HSIL. CONCLUSION: This population of pregnant adolescents had a high incidence of low-grade cervical abnormalities with a high rate of regression. Routinely screening these pregnant adolescents resulted in numerous repeat visits, repeat Pap smears, and colposcopy referrals, and led to patient anxiety and systemic costs. Not a single case of cervical cancer was prevented that would not otherwise have been identified by adherence to the new guidelines. PMID- 26872757 TI - Beyond Alcohol and Tobacco Smoke: Are We Doing Enough to Reduce Fetal Toxicant Exposure? PMID- 26872758 TI - Patient Decision-Making About the Disposition of Surplus Cryopreserved Embryos in Canada. AB - OBJECTIVE: The objective of this study was to identify factors that contribute to patient decision-making for disposition of surplus cryopreserved embryos in Canada. METHODS: In 2013, interviews were conducted with 45 IVF patients from three clinic sites, representing a total of 33 households. Patients interviewed all had unused cryopreserved embryos in storage in 2010. Initial demographic data collection was followed by one in-depth semi-structured interview conducted in 2013. Data were managed and coded thematically. RESULTS: Most patients (21 patients, representing 16 households) renewed storage agreements to keep embryos in storage at the time of the interview. Among patients who did not renew their storage agreements at some point between 2010 and 2013, six patients (representing 5 households) had since used all their embryos, two patients (representing one household) had decided to keep their embryos in storage in perpetuity, three patients (representing 3 households) discarded their embryos outright, and 13 patients (representing 9 households) donated their embryos to research or clinical training. Among patients who donated to research or clinical training, three key themes emerged: a desire to "give back," to contribute to scientific progress, and to avoid "wasting" embryos. These patients were not always certain about whether they had chosen research or clinical training. CONCLUSION: This study demonstrates the applicability of international findings about embryo disposition decision-making to the Canadian setting. Moreover, it identifies that while patients making disposition decisions often choose to donate embryos to research and/or clinical training, they are not always certain about what these options entail. Clinicians, counsellors, and others must ensure that patients are not only aware of their embryo disposition options, but that they understand the nature of these options as well. PMID- 26872759 TI - Future Career Plans and Practice Patterns of Canadian Obstetrics and Gynaecology Residents in 2011. AB - OBJECTIVE: The practice patterns of Obstetricians and Gynaecologists continue to evolve with each new generation of physicians. Diversifying subspecialties, changes in resident duty hours, job market saturation, and desire for work-life balance are playing stronger roles. Professional practice direction and needs assessment may be aided by awareness of future Obstetrics and Gynaecology physician career plans and expectations. The objective of this study was to determine the expected career plans and practice patterns of Canadian Obstetrics and Gynaecology residents following residency. METHODS: The SOGC Junior Member Committee administered its third career planning survey to Canadian Obstetrics and Gynaecology residents electronically in December 2011. The data collected was statistically analyzed and compared to previous surveys. RESULTS: There were 183 responses giving a response rate of 43%. More than one half of all residents were considering postgraduate training (58%). Projected practice patterns included: 84% maintaining obstetrical practice, 60% locuming, and 50% job-sharing. The majority of residents expected to work in a 6 to 10 person call group (48%), work 3 to 5 call shifts per month (72%), work 41 to 60 hours weekly (69%), and practise in a city with a population greater than 500 000 (45%). Only 18% of residents surveyed were in favour of streaming residency programs in Obstetrics and Gynaecology. CONCLUSION: Canadian resident career plan and expected practice pattern assessment remains an important tool for aiding in resource allocation and strategic development of care and training in Obstetrics and Gynaecology in Canada. PMID- 26872760 TI - Spontaneous Pregnancy Following Ulipristal Acetate Treatment in a Woman with a Symptomatic Uterine Fibroid. AB - BACKGROUND: Uterine fibroids (UFs) may impair fertility and promote miscarriage. The optimal treatment for women with UFs who wish to conceive is uncertain. CASE: A 35-year-old woman of African ancestry with a history of recurrent miscarriage (gravida 5, para 0) had a solitary submucosal UF (volume: 102.4 cm(3)) extending into the uterine cavity. Following a three-month course of ulipristal acetate (UPA) 5 mg daily, UF volume decreased to 72.1 cm(3). The patient conceived approximately two months after discontinuing UPA. She had an uncomplicated pregnancy and underwent a planned induction of labour at 38 weeks' gestation. The patient had a normal vaginal delivery of a healthy male infant weighing 3130 g. An ultrasound performed three months post-delivery revealed further reduction in UF volume to 14.5 cm(3). CONCLUSION: This report demonstrates the utility of UPA in the management of women with UFs who desire pregnancy but who opt for non surgical management. PMID- 26872761 TI - Use of Ulipristal Acetate for the Management of Fibroid-Related Acute Abnormal Uterine Bleeding. AB - BACKGROUND: Episodes of acute abnormal uterine bleeding related to uterine fibroids can cause significant morbidity. Traditional management with high-dose hormonal regimens may not be as effective when used in women with fibroids. CASE: A 32-year-old woman with a 12 cm uterine fibroid presented with an episode of acute abnormal uterine bleeding requiring blood transfusion. In lieu of using a hormonal maintenance regimen after the bleeding had stabilized, the patient was treated with ulipristal acetate 5 mg daily for three months. Amenorrhea was induced rapidly and the patient had no further episodes of acute excessive uterine bleeding. She subsequently underwent a laparoscopic myomectomy with a satisfactory outcome. CONCLUSION: Ulipristal acetate has been shown to induce amenorrhea rapidly in women with uterine fibroids, and it can be a useful treatment in the emergency management of fibroid-related acute abnormal uterine bleeding. PMID- 26872762 TI - Joint CAR/SOGC Statement on Performing Ultrasound Examinations of the Female Pelvis. PMID- 26872763 TI - Gender Differences in Heroin Addiction and Treatment: Results from the VEdeTTE Cohort. AB - BACKGROUND: Gender differences strongly affect heroin addiction, from risk factors to patterns of consumption, access to treatments, and outcomes. OBJECTIVES: To investigate gender differences in the VEdeTTE cohort of heroin addicts. METHODS: VEdeTTE is a cohort of 10,454 heroin users enrolled between 1998 and 2001 in 115 public drug treatment centres in Italy. Clinical and personal information were collected at intake through a structured interview. Treatments were recorded using a standardized form. Gender differences were explored with regard to characteristics at intake, treatments, and retention in methadone maintenance and therapeutic community. Cox Proportional models were carried out to identify risk factors for treatment abandon. RESULTS: Compared with men, at their first access to treatment women with drug addiction were younger, more frequently married, legally separated, divorced or widow, unemployed though better educated, HIV+; more frequently they lived with their partner and sons. They reported a higher use of sedatives, but a lower use of alcohol; more frequently they had psychiatric comorbidity, including depression, self-injuries, and suicide attempts. Psychotherapy was more frequently prescribed to women, pharmacological treatments to men. Methadone maintenance was less frequently abandoned by women. Drug abuse severity factors predicted abandon of methadone among women. High methadone doses and the combination with psychotherapy improved treatment retention in both genders. Low education level and severity factors among women and young age among men predicted abandon of therapeutic community. CONCLUSIONS: Gender differences in the VEdeTTE cohort suggest the need of a gender sensitive approach to improve treatment outcomes among heroin addicts. PMID- 26872764 TI - Phase II Study of Concurrent Pemetrexed, Cisplatin, and Radiation Therapy for Stage IIIA/B Unresectable Non-Small Cell Lung Cancer. AB - INTRODUCTION: Concurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non-small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established. PATIENTS AND METHODS: In the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m(2) intravenously on days 1 and 22, 20 mg/m(2) intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg(2)) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1 year OS rate was >= 70%. RESULTS: A total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively. CONCLUSION: Full-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation. PMID- 26872766 TI - Classic Spotlight: Regulatory Function of Leader RNAs. PMID- 26872767 TI - Classic Spotlight: the Birth of the Transcriptional Activator. PMID- 26872765 TI - Proportion of Non-Small-Cell Lung Cancer Patients that Would Have Been Eligible for Lung Cancer Screening. AB - BACKGROUND: Lung cancer screening is recommended for current smokers (CS) and former smokers (FS) who meet specific age and smoking criteria. We used existing criteria to estimate the proportion of non-small-cell lung cancer (NSCLC) patients that would have been screening-eligible. METHODS: We identified 2030 NSCLC patients at our institution from 1994 to 2014 and recorded their cigarette smoking status and history. Using criteria from the United States Preventative Services Task Force (USPSTF) and from other organizations, we ascertained the proportions of screening-eligible patients. Associations among smoking status, gender, race/ethnicity, and insurance type were assessed using Chi-Square test. RESULTS: In our cohort, 31.0% (n = 630) were CS, 43.0% (n = 873) were FS, and 26.0% (n = 527) were never smokers. There were 698 patients (34.4%) who met all USPSTF screening criteria. Among 1503 CS and FS, 77.5% (n = 1165) were between age 55 and 80 years, and 67.9% (n = 1021) had smoked >= 30 pack-years. Among FS, 50.4% (n = 440) had quit within 15 years of diagnosis. Median pack-years smoked was 40 (interquartile range, 20-55 pack-years). CS were more likely to meet screening criteria than FS (67.5% vs. 31.3%; P < .0001). Significant differences were found among individuals meeting criteria by gender, race/ethnicity, and insurance type. CONCLUSION: Only a third of patients diagnosed with NSCLC were eligible for lung cancer screening based on USPSTF criteria. FS were less likely to meet all screening criteria due to only half meeting the quit-time criterion. Additional evidence is needed to evaluate the utility of restricting screening among FS to those who quit within 15 years. PMID- 26872770 TI - MetaSINEs: Broad Distribution of a Novel SINE Superfamily in Animals. AB - SINEs (short interspersed elements) are transposable elements that typically originate independently in each taxonomic clade (order/family). However, some SINE families share a highly similar central sequence and are thus categorized as a SINE superfamily. Although only four SINE superfamilies (CORE-SINEs, V-SINEs, DeuSINEs, and Ceph-SINEs) have been reported so far, it is expected that new SINE superfamilies would be discovered by deep exploration of new SINEs in metazoan genomes. Here we describe 15 SINEs, among which 13 are novel, that have a similar 66-bp central region and therefore constitute a new SINE superfamily, MetaSINEs. MetaSINEs are distributed from fish to cnidarians, suggesting their common evolutionary origin at least 640 Ma. Because the 3' tails of MetaSINEs are variable, these SINEs most likely survived by changing their partner long interspersed elements for retrotransposition during evolution. Furthermore, we examined the presence of members of other SINE superfamilies in bivalve genomes and characterized eight new SINEs belonging to the CORE-SINEs, V-SINEs, and DeuSINEs, in addition to the MetaSINEs. The broad distribution of bivalve SINEs suggests that at least three SINEs originated in the common ancestor of Bivalvia. Our comparative analysis of the central domains of the SINEs revealed that, in each superfamily, only a restricted region is shared among all of its members. Because the functions of the central domains of the SINE superfamilies remain unknown, such structural information of SINE superfamilies will be useful for future experimental and comparative analyses to reveal why they have been retained in metazoan genomes during evolution. PMID- 26872771 TI - A Tale of Genome Compartmentalization: The Evolution of Virulence Clusters in Smut Fungi. AB - Smut fungi are plant pathogens mostly parasitizing wild species of grasses as well as domesticated cereal crops. Genome analysis of several smut fungi including Ustilago maydis revealed a singular clustered organization of genes encoding secreted effectors. In U. maydis, many of these clusters have a role in virulence. Reconstructing the evolutionary history of clusters of effector genes is difficult because of their intrinsically fast evolution, which erodes the phylogenetic signal and homology relationships. Here, we describe the use of comparative evolutionary analyses of quality draft assemblies of genomes to study the mechanisms of this evolution. We report the genome sequence of a South African isolate of Sporisorium scitamineum, a smut fungus parasitizing sugar cane with a phylogenetic position intermediate to the two previously sequenced species U. maydis and Sporisorium reilianum. We show that the genome of S. scitamineum contains more and larger gene clusters encoding secreted effectors than any previously described species in this group. We trace back the origin of the clusters and find that their evolution is mainly driven by tandem gene duplication. In addition, transposable elements play a major role in the evolution of the clustered genes. Transposable elements are significantly associated with clusters of genes encoding fast evolving secreted effectors. This suggests that such clusters represent a case of genome compartmentalization that restrains the activity of transposable elements on genes under diversifying selection for which this activity is potentially beneficial, while protecting the rest of the genome from its deleterious effect. PMID- 26872772 TI - No Distinction of Orthology/Paralogy between Human and Chimpanzee Rh Blood Group Genes. AB - On human (Homo sapiens) chromosome 1, there is a tandem duplication encompassing Rh blood group genes (Hosa_RHD and Hosa_RHCE). This duplication occurred in the common ancestor of humans, chimpanzees (Pan troglodytes), and gorillas, after splitting from their common ancestor with orangutans. Although several studies have been conducted on ape Rh blood group genes, the clear genome structures of the gene clusters remain unknown. Here, we determined the genome structure of the gene cluster of chimpanzee Rh genes by sequencing five BAC (Bacterial Artificial Chromosome) clones derived from chimpanzees. We characterized three complete loci (Patr_RHalpha, Patr_RHbeta, and Patr_RHgamma). In the Patr_RHbeta locus, a short version of the gene, which lacked the middle part containing exons 4-8, was observed. The Patr_RHalpha and Patr_RHbeta genes were located on the locations corresponding to Hosa_RHD and Hosa_RHCE, respectively, and Patr_RHgamma was in the immediate vicinity of Patr_RHbeta. Sequence comparisons revealed high sequence similarity between Patr_RHbeta and Hosa_RHCE, while the chimpanzee Rh gene closest to Hosa_RHD was not Patr_RHalpha but rather Patr_RHgamma. The results suggest that rearrangements and gene conversions frequently occurred between these genes and that the classic orthology/paralogy dichotomy no longer holds between human and chimpanzee Rh blood group genes. PMID- 26872773 TI - Drosophila Females Undergo Genome Expansion after Interspecific Hybridization. AB - Genome size (or C-value) can present a wide range of values among eukaryotes. This variation has been attributed to differences in the amplification and deletion of different noncoding repetitive sequences, particularly transposable elements (TEs). TEs can be activated under different stress conditions such as interspecific hybridization events, as described for several species of animals and plants. These massive transposition episodes can lead to considerable genome expansions that could ultimately be involved in hybrid speciation processes. Here, we describe the effects of hybridization and introgression on genome size of Drosophila hybrids. We measured the genome size of two close Drosophila species, Drosophila buzzatii and Drosophila koepferae, their F1 offspring and the offspring from three generations of backcrossed hybrids; where mobilization of up to 28 different TEs was previously detected. We show that hybrid females indeed present a genome expansion, especially in the first backcross, which could likely be explained by transposition events. Hybrid males, which exhibit more variable C values among individuals of the same generation, do not present an increased genome size. Thus, we demonstrate that the impact of hybridization on genome size can be detected through flow cytometry and is sex-dependent. PMID- 26872776 TI - Nobel official resigns in wake of storm over Italian surgeon. PMID- 26872774 TI - A Comparative Analysis of Mitochondrial Genomes in Eustigmatophyte Algae. AB - Eustigmatophyceae (Ochrophyta, Stramenopiles) is a small algal group with species of the genus Nannochloropsis being its best studied representatives. Nuclear and organellar genomes have been recently sequenced for several Nannochloropsis spp., but phylogenetically wider genomic studies are missing for eustigmatophytes. We sequenced mitochondrial genomes (mitogenomes) of three species representing most major eustigmatophyte lineages, Monodopsis sp. MarTras21, Vischeria sp. CAUP Q 202 and Trachydiscus minutus, and carried out their comparative analysis in the context of available data from Nannochloropsis and other stramenopiles, revealing a number of noticeable findings. First, mitogenomes of most eustigmatophytes are highly collinear and similar in the gene content, but extensive rearrangements and loss of three otherwise ubiquitous genes happened in the Vischeria lineage; this correlates with an accelerated evolution of mitochondrial gene sequences in this lineage. Second, eustigmatophytes appear to be the only ochrophyte group with the Atp1 protein encoded by the mitogenome. Third, eustigmatophyte mitogenomes uniquely share a truncated nad11 gene encoding only the C-terminal part of the Nad11 protein, while the N-terminal part is encoded by a separate gene in the nuclear genome. Fourth, UGA as a termination codon and the cognate release factor mRF2 were lost from mitochondria independently by the Nannochloropsis and T. minutus lineages. Finally, the rps3 gene in the mitogenome of Vischeria sp. is interrupted by the UAG codon, but the genome includes a gene for an unusual tRNA with an extended anticodon loop that we speculate may serve as a suppressor tRNA to properly decode the rps3 gene. PMID- 26872775 TI - Evolutionary Changes on the Way to Clathrin-Mediated Endocytosis in Animals. AB - Endocytic pathways constitute an evolutionarily ancient system that significantly contributed to the eukaryotic cell architecture and to the diversity of cell type specific functions and signaling cascades, in particular of metazoans. Here we used comparative proteomic studies to analyze the universal internalization route in eukaryotes, clathrin-mediated endocytosis (CME), to address the issues of how this system evolved and what are its specific features. Among 35 proteins crucially required for animal CME, we identified a subset of 22 proteins common to major eukaryotic branches and 13 gradually acquired during evolution. Based on exploration of structure-function relationship between conserved homologs in sister, distantly related and early diverged branches, we identified novel features acquired during evolution of endocytic proteins on the way to animals: Elaborated way of cargo recruitment by multiple sorting proteins, structural changes in the core endocytic complex AP2, the emergence of the Fer/Cip4 homology domain-only protein/epidermal growth factor receptor substrate 15/intersectin functional complex as an additional interaction hub and activator of AP2, as well as changes in late endocytic stages due to recruitment of dynamin/sorting nexin 9 complex and involvement of the actin polymerization machinery. The evolutionary reconstruction showed the basis of the CME process and its subsequent step-by step development. Documented changes imply more precise regulation of the pathway, as well as CME specialization for the uptake of specific cargoes and cell type-specific functions. PMID- 26872777 TI - What is grounded theory? PMID- 26872778 TI - Novel Approaches for Diagnosing Melanoma Skin Lesions Through Supervised and Deep Learning Algorithms. AB - Dermoscopy is a technique used to capture the images of skin, and these images are useful to analyze the different types of skin diseases. Malignant melanoma is a kind of skin cancer whose severity even leads to death. Earlier detection of melanoma prevents death and the clinicians can treat the patients to increase the chances of survival. Only few machine learning algorithms are developed to detect the melanoma using its features. This paper proposes a Computer Aided Diagnosis (CAD) system which equips efficient algorithms to classify and predict the melanoma. Enhancement of the images are done using Contrast Limited Adaptive Histogram Equalization technique (CLAHE) and median filter. A new segmentation algorithm called Normalized Otsu's Segmentation (NOS) is implemented to segment the affected skin lesion from the normal skin, which overcomes the problem of variable illumination. Fifteen features are derived and extracted from the segmented images are fed into the proposed classification techniques like Deep Learning based Neural Networks and Hybrid Adaboost-Support Vector Machine (SVM) algorithms. The proposed system is tested and validated with nearly 992 images (malignant & benign lesions) and it provides a high classification accuracy of 93 %. The proposed CAD system can assist the dermatologists to confirm the decision of the diagnosis and to avoid excisional biopsies. PMID- 26872779 TI - Differential Privacy Preserving in Big Data Analytics for Connected Health. AB - In Body Area Networks (BANs), big data collected by wearable sensors usually contain sensitive information, which is compulsory to be appropriately protected. Previous methods neglected privacy protection issue, leading to privacy exposure. In this paper, a differential privacy protection scheme for big data in body sensor network is developed. Compared with previous methods, this scheme will provide privacy protection with higher availability and reliability. We introduce the concept of dynamic noise thresholds, which makes our scheme more suitable to process big data. Experimental results demonstrate that, even when the attacker has full background knowledge, the proposed scheme can still provide enough interference to big sensitive data so as to preserve the privacy. PMID- 26872780 TI - Bringing Medicine to the Digital Age via Hackathons and Beyond. AB - Health care technology and innovation is a rapidly growing industry with great potential. Hackathons have become an increasingly popular venue for institutions to generate ideas and enthusiasm for innovation. These events can inspire change and eventual improvement in medical systems. However, alongside developers and business-savvy entrepreneurs, the ongoing participation by health care providers and researchers is essential for the careful development, implementation and evaluation of any technological intervention. PMID- 26872782 TI - Toward Proper Authentication Methods in Electronic Medical Record Access Compliant to HIPAA and C.I.A. Triangle. AB - This paper examines various methods encompassing the authentication of users in accessing Electronic Medical Records (EMRs). From a methodological perspective, multiple authentication methods have been researched from both a desktop and mobile accessibility perspective. Each method is investigated at a high level, along with comparative analyses, as well as real world examples. The projected outcome of this examination is a better understanding of the sophistication required in protecting the vital privacy constraints of an individual's Protected Health Information (PHI). In understanding the implications of protecting healthcare data in today's technological world, the scope of this paper is to grasp an overview of confidentiality as it pertains to information security. In addressing this topic, a high level overview of the three goals of information security are examined; in particular, the goal of confidentiality is the primary focus. Expanding upon the goal of confidentiality, healthcare accessibility legal aspects are considered, with a focus upon the Health Insurance Portability and Accountability Act of 1996 (HIPAA). With the primary focus of this examination being access to EMRs, the paper will consider two types of accessibility of concern: access from a physician, or group of physicians; and access from an individual patient. PMID- 26872781 TI - Feasibility and Preliminary Outcomes of a Web and Smartphone-Based Medication Self-Management Platform for Chronically Ill Patients. AB - OBJECTIVE: The aim of this study was to assess the feasibility and preliminary outcomes of a medication self-management platform for chronically ill patients, Medplan. METHODS: We performed a 6-month single-arm prospective pre-post intervention study of patients receiving treatment for hypertension and/or dyslipidemia and/or heart failure and/or human immunodeficiency virus infection. During the pre-intervention phase, participants were followed according to their usual care; during the intervention phase, they used Medplan. We evaluated adherence, health outcomes, healthcare resources and measured the satisfaction of patients and health care professionals. RESULTS: The study population comprised 42 patients. No differences were found in adherence to medication measured by proportion of days covered with medication (PDC). However, when adherence was measured using the SMAQ, the percentage of adherent patients improved during the intervention phase (p < 0.05), and the number of days with missed doses decreased (p < 0.05). Adherence measured using the Medplan app showed poor concordance with PDC. No differences were found in health outcomes or in the use of health care resources during the study period. The mean satisfaction score for Medplan was 7.2 +/- 2.7 out of 10 among patients and 7.3 +/- 1.7 among health care professionals. In fact, 71.4 % of participants said they would recommend the app to a friend, and 88.1 % wanted to continue using it. CONCLUSION: The Medplan platform proved to be feasible and was well accepted by its users. However, its impact on adherence differed depending on the assessment method. The lack of effect on PDC is mainly because patients were already good adherers at baseline. The study enabled us to validate the platform in real patients using many different mobile devices and to identify potential barriers to scaling up the platform. PMID- 26872783 TI - PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. AB - Entry into mitosis is driven by the phosphorylation of thousands of substrates, under the master control of Cdk1. During entry into mitosis, Cdk1, in collaboration with MASTL kinase, represses the activity of the major mitotic protein phosphatases, PP1 and PP2A, thereby ensuring mitotic substrates remain phosphorylated. For cells to complete and exit mitosis, these phosphorylation events must be removed, and hence, phosphatase activity must be reactivated. This reactivation of phosphatase activity presumably requires the inhibition of MASTL; however, it is not currently understood what deactivates MASTL and how this is achieved. In this study, we identified that PP1 is associated with, and capable of partially dephosphorylating and deactivating, MASTL during mitotic exit. Using mathematical modelling, we were able to confirm that deactivation of MASTL is essential for mitotic exit. Furthermore, small decreases in Cdk1 activity during metaphase are sufficient to initiate the reactivation of PP1, which in turn partially deactivates MASTL to release inhibition of PP2A and, hence, create a feedback loop. This feedback loop drives complete deactivation of MASTL, ensuring a strong switch-like activation of phosphatase activity during mitotic exit. PMID- 26872785 TI - Integrins synergise to induce expression of the MRTF-A-SRF target gene ISG15 for promoting cancer cell invasion. AB - Integrin-mediated activation of small GTPases induces the polymerisation of G actin into various actin structures and the release of the transcriptional co activator MRTF from G-actin. Here we report that pan-integrin-null fibroblasts seeded on fibronectin and expressing beta1- and/or alphaV-class integrin contained different G-actin pools, nuclear MRTF-A (also known as MKL1 or MAL) levels and MRTF-A-SRF activities. The nuclear MRTF-A levels and activities were highest in cells expressing both integrin classes, lower in cells expressing beta1 integrins and lowest in cells expressing the alphaV integrins. Quantitative proteomics and transcriptomics analyses linked the differential MRTF-A activities to the expression of the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), which is known to modify focal adhesion and cytoskeletal proteins. The malignant breast cancer cell line MDA-MB-231 expressed high levels of beta1 integrins, ISG15 and ISGylated proteins, which promoted invasive properties, whereas non-invasive MDA-MB-468 and MCF-7 cell lines expressed low levels of beta1 integrins, ISG15 and ISGylated proteins. Our findings suggest that integrin adhesion-induced MRTF-A-SRF activation and ISG15 expression constitute a newly discovered signalling circuit that promotes cell migration and invasion. PMID- 26872784 TI - TRAF2 exerts opposing effects on basal and TNFalpha-induced activation of the classic IKK complex in hematopoietic cells in mice. AB - The role of TRAF2 and TRAF5 in TNFalpha-induced NF-kappaB activation has become complicated owing to the accumulation of conflicting data. Here, we report that 7 day-old TRAF2-knockout (KO) and TRAF2 TRAF5 double KO (TRAF2/5-DKO) mice exhibit enhanced canonical IkappaB kinase (IKK) and caspase-8 activation in spleen and liver, and that subsequent knockout of TNFalpha suppresses the basal activity of caspase-8, but not of IKK. In primary TRAF2 KO and TRAF2/5-DKO cells, TNFalpha induced immediate IKK activation is impaired, whereas delayed IKK activation occurs normally; as such, owing to elevated basal and TNFalpha-induced delayed IKK activation, TNFalpha stimulation leads to significantly increased induction of a subset of NF-kappaB-dependent genes in these cells. In line with this, both TRAF2 KO and TRAF2/5-DKO mice succumb to a sublethal dose of TNFalpha owing to increased expression of NF-kappaB target genes, diarrhea and bradypnea. Notably, depletion of IAP1 and IAP2 (also known as BIRC2 and BIRC3, respectively) also results in elevated basal IKK activation that is independent of autocrine TNFalpha production and that impairs TNFalpha-induced immediate IKK activation. These data reveal that TRAF2, IAP1 and IAP2, but not TRAF5, cooperatively regulate basal and TNFalpha-induced immediate IKK activation. PMID- 26872786 TI - DNA replication initiator Cdc6 also regulates ribosomal DNA transcription initiation. AB - RNA-polymerase-I-dependent ribosomal DNA (rDNA) transcription is fundamental to rRNA processing, ribosome assembly and protein synthesis. However, how this process is initiated during the cell cycle is not fully understood. By performing a proteomic analysis of transcription factors that bind RNA polymerase I during rDNA transcription initiation, we identified that the DNA replication initiator Cdc6 interacts with RNA polymerase I and its co-factors, and promotes rDNA transcription in G1 phase in an ATPase-activity-dependent manner. We further showed that Cdc6 is targeted to the nucleolus during late mitosis and G1 phase in a manner that is dependent on B23 (also known as nucleophosmin, NPM1), and preferentially binds to the rDNA promoter through its ATP-binding domain. Overexpression of Cdc6 increases rDNA transcription, whereas knockdown of Cdc6 results in a decreased association of both RNA polymerase I and the RNA polymerase I transcription factor RRN3 with rDNA, and a reduction of rDNA transcription. Furthermore, depletion of Cdc6 impairs the interaction between RRN3 and RNA polymerase I. Taken together, our data demonstrate that Cdc6 also serves as a regulator of rDNA transcription initiation, and indicate a mechanism by which initiation of rDNA transcription and DNA replication can be coordinated in cells. PMID- 26872787 TI - Tailored placement of a turn-forming PA tag into the structured domain of a protein to probe its conformational state. AB - Placement of a tag sequence is usually limited to either terminal end of the target protein, reducing the potential of epitope tags for various labeling applications. The PA tag is a dodecapeptide (GVAMPGAEDDVV) that is recognized by a high-affinity antibody NZ-1. We determined the crystal structure of the PA-tag NZ-1 complex and found that NZ-1 recognizes a central segment of the PA tag peptide in a tight beta-turn configuration, suggesting that it is compatible with the insertion into a loop. This possibility was tested and confirmed using multiple integrin subunits and semaphorin. More specifically, the PA tag can be inserted at multiple locations within the integrin alphaIIb subunit (encoded by ITGA2B) of the fibrinogen receptor alphaIIbbeta3 integrin (of which the beta3 subunit is encoded by ITGB3) without affecting the structural and functional integrity, while maintaining its high affinity for NZ-1. The large choice of the sites for 'epitope grafting' enabled the placement of the PA tag at a location whose accessibility is modulated during the biological action of the receptor. Thus, we succeeded in converting a general anti-tag antibody into a special anti integrin antibody that can be classified as a ligand-induced binding site antibody. PMID- 26872788 TI - Intratumoral heterogeneity of (18)F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma. AB - PURPOSE: To assess whether intratumoral heterogeneity measured by (18)F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment (18)F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. RESULTS: The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. CONCLUSION: Intratumoral heterogeneity of (18)F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters. PMID- 26872790 TI - Visceral leishmaniasis, hypertriglyceridemia and secondary hemophagocytic lymphohistiocytosis. PMID- 26872789 TI - Analysis of pairwise correlations in multi-parametric PET/MR data for biological tumor characterization and treatment individualization strategies. PMID- 26872792 TI - Neurotropic infiltration and neuropathy of multifocal lymphoma. PMID- 26872791 TI - Trends in anemia treatment among patients with five non-myeloid malignancies treated with chemotherapy in a large integrated health care delivery system in California, 2000-2013. AB - PURPOSE: The aim of this study is to examine treatment patterns for chemotherapy induced anemia (CIA) between calendar periods when the changes in the US prescribing information, for erythropoiesis-stimulating agents (ESAs) took place. METHODS: Patients diagnosed with breast, lung, colorectal, ovarian, or gastric cancer (2000-2012) who developed grade 2+ CIA (hemoglobin (Hb) <10 g/dl) were identified from Kaiser Permanente Southern California Health Plan. We estimated the proportions of CIA episodes with ESA use, red blood cell (RBC) transfusion, or prescription nutritional supplements in three calendar periods: January 1, 2000-December 31, 2006 (P1), January 1, 2007-March 24, 2010 (P2), and March 25, 2010-June 30, 2013 (P3). Multivariable regressions were used to test the differences of CIA treatment approaches and Hb concentration prior to CIA treatment across these calendar periods. RESULTS: The proportions of CIA episodes with ESA use were 28 % in P1, 21 % in P2, and 3 % in P3. For RBC transfusion, they were 8 % in P1, 14 % in P2 and 16 % in P3. The trend of decreasing ESA use and increasing transfusion use were statistically significant. Relative to P1, the odds ratio (OR) was 0.69 (95% CI: 0.55, 0.86) for P2 and 0.08 (0.30, 0.88) for P3 for ESA use. For RBC transfusion, OR was 2.00 (1.56, 2.56) for P2 and 2.37 (1.88, 3.00) for P3. Use of prescription nutritional supplement was rare across calendar periods. There was a decreasing trend of Hb concentration prior to ESA use (p value <0.01), but no difference in Hb concentrations prior to transfusion. CONCLUSION: In the management of CIA, use of ESA has decreased over time, while use of RBC transfusion has increased. PMID- 26872795 TI - Spray drying of lipid-based systems loaded with Camellia sinensis polyphenols. AB - In this work, spray-dried lipid systems based on soy phosphatidylcholine, cholesterol and lauroyl polyoxylglycerides for entrapping Green tea polyphenols were produced. The aim was to study the effects of the encapsulating composition and spray drying conditions on the system performance and physicochemical product properties. The spray dryer powder production yield falls around 50.7 +/- 2.8%, which is typical for lab scale spray dryers. Wrinkled and rounded particles, with low surface porosities were generated, independent of the drying carriers (trehalose or lactose) used. The product showed high encapsulation efficiency of Green tea polyphenols, which was promptly redispersible in water. It presented low density, and good compressive and flow properties. The results herein reported confirm the feasibility of the entrapment of Green tea polyphenols in lipid-based compositions by spray drying in presence of the drying carriers evaluated. The spray-dried microparticles show high potential to be used as additive in food, nutraceutical and pharmaceutical products. PMID- 26872794 TI - First structure of archaeal branched-chain amino acid aminotransferase from Thermoproteus uzoniensis specific for L-amino acids and R-amines. AB - The gene TUZN1299 from the genome of the hyperthermophilic archaeon Thermoproteus uzoniensis encoding a new 32.8 kDa branched-chain amino acid aminotransferase (BCAT) was expressed in Escherichia coli. The recombinant protein TUZN1299 was purified to homogeneity in the PLP-bound form. TUZN1299 was active towards branched-chain amino acids (L-Val, L-Leu, L-Ile) and showed low but detectable activity toward (R)-alpha-methylbenzylamine. The enzyme exhibits high-temperature optimum, thermal stability, and tolerance to organic solvents. The structure of an archaeal BCAT called TUZN1299 was solved for the first time (at 2.0 A resolution). TUZN1299 has a typical BCAT type IV fold, and the organization of its active site is similar to that of bacterial BCATs. However, there are some differences in the amino acid composition of the active site. PMID- 26872793 TI - The unmet supportive care needs-what advanced lung cancer patients' caregivers need and related factors. AB - PURPOSE: To identify the unmet supportive care needs and related factors in caregivers of patients with advanced lung cancer. METHODS: A cross-sectional study of 166 lung cancer patient-caregivers dyads was recruited at a medical center. The supportive care needs, fatigue, and sleep disturbance of caregivers were collected. Patients were assessed for symptom severity, anxiety, and depression. Logistic regression was used to reveal the related factors of unmet supportive care needs. RESULTS: Of the 166 dyads surveyed, the top unmet needs were information needs, health care professional/health care service needs, and daily living needs. Patients' anxiety was positively correlated to overall caregiving needs, health care professional/health care service needs, interpersonal communication needs, and psychological/emotional needs of caregivers. The information needs and health care professional/health care service needs were related to the caregivers' fatigue. The sleep disturbance of caregivers was associated with their overall caregiving needs, daily living needs, and psychological/emotional needs. CONCLUSIONS: Future interventions to meet the needs of caregivers should include specific needs assessment and continuing education in caregiving. PMID- 26872796 TI - Using LEADS to shift to high performance. AB - Health systems across Canada are tasked to measure results of all their strategic initiatives. Included in most strategic plans is leadership development. How to measure leadership effectiveness in relation to organizational objectives is key in determining organizational effectiveness. The following findings offer considerations for a 21(st)-century approach to shifting to high-performance systems. PMID- 26872797 TI - Exploring distributed leadership in the BC Sepsis Network. AB - Commissioned research was undertaken to explore the role of networks in supporting large-scale change and improvement. Participatory action research and social network analysis were used to study the BC Sepsis Network. Findings of this research include insights into distributed leadership, enablers and barriers within a network approach; the importance of relationships and trust; and the need for meaningful and timely data. Recommendations are made for health leaders who are considering utilizing networks for improving patient quality and safety. PMID- 26872798 TI - Health reform in Canada: Enabling perspectives for health leadership. AB - Canadian healthcare leaders are experiencing unprecedented change. In Canada and worldwide, efforts are being made to create patient-centred service delivery models. In order to participate fully in that transformation, leaders must embrace the new leadership responsibilities vital to patient-centred change. To fail to do so will marginalize their role or render them irrelevant. This article reviews literature in the past 5 years to outline the change context for leaders and what they can do to enhance their effectiveness. Leaders are encouraged to redouble their efforts to develop their leadership capacity, engage physicians as partners, embrace complexity, engage the patient and public in reform efforts, and embrace appropriate technological trends within the consumer community. To reinvent leadership supportive of patient-centred change, healthcare leaders need to act individually to grow their own capacity and collectively to take control of the leadership needed in order to fulfill their role in change. PMID- 26872799 TI - If we don't change direction soon, we'll end up where we're going. AB - Change management initiatives are a key focus of healthcare systems across the country. This commentary, written by a former health minister, looks at change from the perspective of senior decision-makers. The need to directly link change management activities to broader transformation necessary to improve outcomes and ensure sustainability of healthcare in Canada is discussed. Suggestions for elements of a national transformation agenda, key enablers required to ensure the best change initiatives are leveraged across healthcare systems, and questions that should be asked by leaders in the evaluation of change initiatives are proposed. PMID- 26872800 TI - The role of change management in the District Health Authority Consolidation (Transition and Design) project in Nova Scotia. AB - The District Health Authority Consolidation (Transition and Design) project in Nova Scotia was initiated to consolidate the existing nine district health authorities into one provincial health authority. This article provides an overview of the internal change management approach and activities that were developed to support the various phases of the design and transition process. Three phases of work are outlined, and specific change management activities are described as are lessons learned from the overall approach. PMID- 26872801 TI - Gamification as a strategy to engage and motivate clinicians to improve care. AB - Approaching change through seeking commitment rather than requiring compliance is an effective way to promote desired behaviours in healthcare. Gamification was explored as a technique to engage clinicians in the adoption of sepsis identification and management tools. Positive extrinsic (eg, feedback and rewards) and intrinsic (eg, mastery, autonomy, relatedness, and purpose) motivators were integrated into a campaign to save lives, leading to a significant reduction in severe sepsis mortality and improvement in processes of care. PMID- 26872802 TI - Putting children first: An opportunity for Canada's new government. AB - For more than 50 years, the importance of studying new medicines in childhood has been widely recognized. Nonetheless, Health Canada has eschewed policies requiring such evaluation, despite effective reforms elsewhere. In 2012, the Council of Canadian Academies convened an expert panel to assess Canada's research base for labelling of pediatric therapies. The September 2014 report has not yet resulted in action, but it deserves consideration by the new government with timely recognition of the high priority that evidence-based treatment of children deserves. PMID- 26872803 TI - Simulating hypoxia-induced acidic environment in cancer cells facilitates mobilization and redox-cycling of genomic copper by daidzein leading to pro oxidant cell death: implications for the sensitization of resistant hypoxic cancer cells to therapeutic challenges. AB - This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper dependant pathway in which endogenous copper is mobilized by daidzein and redox cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens. PMID- 26872804 TI - Risk of skin cancer in multiple myeloma patients: a retrospective cohort study. AB - Immunosuppressed patients are known to have an increased incidence of skin cancer. Patients with multiple myeloma (MM) show impaired immune function. In the past, because of poor survival, the incidence of specific secondary primary malignancies such as skin cancer among these patients was difficult to establish. With more effective MM therapies that have emerged in recent years, these patients are living markedly longer, and therefore, it becomes of increasing importance to determine whether their risk of developing other medical problems such as skin cancer is increased. We performed a retrospective cohort study of 205 myeloma patients and 193 age-, race-, and gender-matched control subjects to assess the incidence of skin cancers among patients with MM and determine the specific types of and risk factors for skin cancer. We found that there is an increased occurrence of skin cancer among patients with MM compared to control subjects (26.8% vs. 16.1% in controls; P = 0.009). Among specific types of skin cancer, the proportion of patients with squamous cell carcinoma (SCC) was higher than controls (P = 0.016). In addition to MM diagnosis, older age and Caucasian ethnicity were predictors of skin cancer of any type. Furthermore, older age was also a predictor of SCC. PMID- 26872805 TI - Perfusion and metabolic scintigraphy with (123)I-BMIPP in prognosis of cardiac resynchronization therapy in patients with dilated cardiomyopathy. AB - OBJECTIVE: The objective of the study was to investigate the left ventricular (LV) myocardial perfusion and metabolism in patients with idiopathic dilated cardiomyopathy (DCM) and to identify the scintigraphic predictors of the efficacy of cardiac resynchronization therapy (CRT). METHODS: The study comprised 63 patients with DCM and severe heart failure (NYHA class III-IV). Before CRT, all patients received gamma-scintigraphy with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) and with (123)I-beta-methyl-iodophenyl pentadecanoic acid ((123)I BMIPP) for evaluation of myocardial perfusion and metabolism, respectively. Before and after 6 months of CRT, all patients underwent echocardiography study to assess cardiac hemodynamics. RESULTS: After 6 months of CRT, patients were divided into two groups: group 1 comprised responders in whom LV end systolic volume (LVESV) decreased by >=15 % (n = 39); group 2 comprised non-responders in whom LVESV decreased by <15 % (n = 24). Before CRT, LV pumping function did not significantly differ between groups. Significant differences were found in the following preoperative scintigraphic parameters: myocardial perfusion defect size [7.4 % (5.9; 13.2) % and 11.8 (8.8; 16.2) %, p < 0.05] and metabolic defect size [7.4 (4.4; 14.7) % and 8.8 (8.8; 17.6) %, p < 0.05]. Metabolic scintigraphy showed greater diagnostic efficacy in determining the indications for CRT compared with perfusion scintigraphy [areas under the ROC curves (AUC) of 0.722 and 0.612, respectively]. The best metabolic defect size threshold value of 7.35 % predicted CRT efficacy with the sensitivity and specificity rates of 77.8 and 66.7 %, respectively. CONCLUSION: Data of metabolic scintigraphy may be useful for the integrated prediction of CRT efficacy. PMID- 26872806 TI - Design and evaluation of an interactive training system for scrub nurses. AB - OBJECTIVE: The current trend toward increasingly integrated technological support systems and the rise of streamlined processes in the OR have led to a growing demand for personnel with higher levels of training. Although simulation systems are widely used and accepted in surgical training, they are practically non existent for perioperative nursing, especially scrub nursing. This paper describes and evaluates an interactive OR environment simulation to help train scrub nurses. METHODS: A system comprising multiple computers and monitors, including an interactive table and a touchscreen combined with a client-server software solution, was designed to simulate a scrub nurse's workplace. The resulting demonstrator was evaluated under laboratory conditions with a multicenter interview study involving three participating ear, nose, and throat (ENT) departments in Germany and Switzerland. RESULTS: The participant group of 15 scrub nurses had an average of 12.8 years hands-on experience in the OR. A series of 22 questions was used to evaluate various aspects of the demonstrator system and its suitability for training novices. DISCUSSION: The system received very positive feedback. The participants stated that familiarization with instrument names and learning the instrument table setup were the two most important technical topics for beginners. They found the system useful for acquiring these skills as well as certain non-technical aspects. CONCLUSIONS: Interactive training through simulation is a new approach for preparing novice scrub nurses for the challenges at the instrument table in the OR. It can also improve the lifelong training of perioperative personnel. The proposed system is currently unique in its kind. It can be used to train both technical and non technical skills and, therefore, contributes to patient safety. Moreover, it is not dependent on a specific type of surgical intervention or medical discipline. PMID- 26872807 TI - A novel toolpath force prediction algorithm using CAM volumetric data for optimizing robotic arthroplasty. AB - PURPOSE: Robotic total hip arthroplasty is a procedure in which milling operations are performed on the femur to remove material for the insertion of a prosthetic implant. The robot performs the milling operation by following a sequential list of tool motions, also known as a toolpath, generated by a computer-aided manufacturing (CAM) software. The purpose of this paper is to explain a new toolpath force prediction algorithm that predicts cutting forces, which results in improving the quality and safety of surgical systems. METHODS: With a custom macro developed in the CAM system's native application programming interface, cutting contact patch volume was extracted from CAM simulations. A time domain cutting force model was then developed through the use of a cutting force prediction algorithm. The second portion validated the algorithm by machining a hip canal in simulated bone using a CNC machine. Average cutting forces were measured during machining using a dynamometer and compared to the values predicted from CAM simulation data using the proposed method. RESULTS: The results showed the predicted forces matched the measured forces in both magnitude and overall pattern shape. However, due to inconsistent motion control, the time duration of the forces was slightly distorted. Nevertheless, the algorithm effectively predicted the forces throughout an entire hip canal procedure. CONCLUSION: This method provides a fast and easy technique for predicting cutting forces during orthopedic milling by utilizing data within a CAM software. PMID- 26872808 TI - Successful learning of surgical liver anatomy in a computer-based teaching module. AB - AIM: To analyze factors influencing the learning of surgical liver anatomy in a computer-based teaching module (TM). METHODS: Medical students in their third to fifth year of training (N [Formula: see text] 410) participated in three randomized trials, each with a different primary hypothesis, comparing two- (2D) and three-dimensional (3D) presentation modes in a TM for surgical liver anatomy. Computed tomography images were presented according to the study and allocation group. Students had to answer eleven questions on surgical liver anatomy and four evaluative questions. Scores and time taken to answer the questions were automatically recorded. Since the three studies used the same 15 questions in the TM, a pooled analysis was performed to compare learning factors across studies. RESULTS: 3D groups had higher scores (7.5 +/- 1.7 vs. 5.6 +/- 2.0; p < 0.001) and needed less time (503.5 +/- 187.4 vs. 603.1 +/- 246.7 s; p < 0.001) than 2D groups. Intensive training improved scores in 2D (p < 0.001). Men gave more correct answers than women, independent of presentation mode (7.2 +/- 2.0 vs. 6.5 +/- 2.1; p [Formula: see text] 0.003). An overall association was found between having fun and higher scores in 11 anatomical questions (p < 0.001). In subgroup analysis, 3D groups had more fun than 2D groups (84.7 vs. 65.1 %; p < 0.001). If given the option, more students in the 2D groups (58.9 %) would have preferred a 3D presentation than students in the 3D group (35.9 %) would have preferred 2D (p < 0.001). CONCLUSION: 3D was superior to 2D for learning of surgical liver anatomy. With training 2D showed similar results. Fun and gender were relevant factors for learning success. PMID- 26872809 TI - An all-joint-control master device for single-port laparoscopic surgery robots. AB - PURPOSE: Robots for single-port laparoscopic surgery (SPLS) typically have all of their joints located inside abdomen during surgery, whereas with the da Vinci system, only the tip part of the robot arm is inserted and manipulated. A typical master device that controls only the tip with six degrees of freedom (DOFs) is not suitable for use with SPLS robots because of safety concerns. METHODS: We designed an ergonomic six-DOF master device that can control all of the joints of an SPLS robot. We matched each joint of the master, the slave, and the human arm to decouple all-joint motions of the slave robot. Counterbalance masses were used to reduce operator fatigue. Mapping factors were determined based on kinematic analysis and were used to achieve all-joint control with minimal error at the tip of the slave robot. RESULTS: The proposed master device has two noteworthy features: efficient joint matching to the human arm to decouple each joint motion of the slave robot and accurate mapping factors, which can minimize the trajectory error of the tips between the master and the slave. CONCLUSIONS: We confirmed that the operator can manipulate the slave robot intuitively with the master device and that both tips have similar trajectories with minimal error. PMID- 26872810 TI - Endoscopic scene labelling and augmentation using intraoperative pulsatile motion and colour appearance cues with preoperative anatomical priors. AB - PURPOSE: Despite great advances in medical image segmentation, the accurate and automatic segmentation of endoscopic scenes remains a challenging problem. Two important aspects have to be considered in segmenting an endoscopic scene: (1) noise and clutter due to light reflection and smoke from cutting tissue, and (2) structure occlusion (e.g. vessels occluded by fat, or endophytic tumours occluded by healthy kidney tissue). METHODS: In this paper, we propose a variational technique to augment a surgeon's endoscopic view by segmenting visible as well as occluded structures in the intraoperative endoscopic view. Our method estimates the 3D pose and deformation of anatomical structures segmented from 3D preoperative data in order to align to and segment corresponding structures in 2D intraoperative endoscopic views. Our preoperative to intraoperative alignment is driven by, first, spatio-temporal, signal processing based vessel pulsation cues and, second, machine learning based analysis of colour and textural visual cues. To our knowledge, this is the first work that utilizes vascular pulsation cues for guiding preoperative to intraoperative registration. In addition, we incorporate a tissue-specific (i.e. heterogeneous) physically based deformation model into our framework to cope with the non-rigid deformation of structures that occurs during the intervention. RESULTS: We validated the utility of our technique on fifteen challenging clinical cases with 45 % improvements in accuracy compared to the state-of-the-art method. CONCLUSIONS: A new technique for localizing both visible and occluded structures in an endoscopic view was proposed and tested. This method leverages both preoperative data, as a source of patient-specific prior knowledge, as well as vasculature pulsation and endoscopic visual cues in order to accurately segment the highly noisy and cluttered environment of an endoscopic video. Our results on in vivo clinical cases of partial nephrectomy illustrate the potential of the proposed framework for augmented reality applications in minimally invasive surgeries. PMID- 26872812 TI - The contributions of the tissue inhibitor of metalloproteinase-1 genotypes to triple negative breast cancer risk. AB - The tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins which have been shown to be upregulated in various types of cancers. However, the contribution of TIMPs in breast cancer is not fully understood, not to mention triple negative breast cancer (TNBC). This study's aim was to evaluate the contribution of TIMP-1 rs4898, rs6609533, and rs2070584 genotypes to the risk of breast cancer, especially the subtype of TNBC. The contributions of these TIMP-1 genotypes to cancer risk were examined among 1232 breast cancer patients and 1232 healthy controls, and several clinicopathologic factors were also analyzed. The results showed that the percentages of CC, CT, and TT of TIMP-1 rs4898 were differentially distributed at 28.5%, 33.1% and 38.4% in the breast cancer patient group and 34.5%, 41.0% and 24.5% in the control group, respectively (P for trend = 7.99*10(-13)). It was also found that the CC genotype carriers were of increased risk for breast cancer (odds ratio = 1.90, 95% confidence interval = 1.55-2.33, P = 0.0001) than the TT genotype carriers. In addition, we analyzed the allelic frequency distributions of all three TIMP 1s, and the results showed that the C allele of TIMP-1 rs4898 contributes to an increase in breast cancer susceptibility (P = 2.41*10(-12)). On the other hand, there was no difference found in the distribution of genotypic or allelic frequencies among the patients and the controls for TIMP-1 rs6609533 and rs2070584. Thus, it is our conclusion that the CC genotype of TIMP-1 rs4898 compared to the TT wild-type genotype may increase the risk for breast cancer, especially TNBC in Taiwan, and may serve as an early detective and predictive marker. PMID- 26872811 TI - Dietary components as epigenetic-regulating agents against cancer. AB - Carcinogenesis is a complicated process that involves the deregulation of epigenetics resulting in cellular transformational events, such proliferation, differentiation, and metastasis. Epigenetic machinery changes the accessibility of chromatin to transcriptional regulation through DNA modification. The collaboration of epigenetics and gene transcriptional regulation creates a suitable microenvironment for cancer development, which is proved by the alternation in cell proliferation, differentiation, division, metabolism, DNA repair and movement. Therefore, the reverse of epigenetic dysfunction may provide a possible strategy and new therapeutic targets for cancer treatment. Many dietary components such as sulforaphane and epigallocatechin- 3-gallate have been demonstrated to exert chemopreventive influences, such as reducing tumor growth and enhancing cancer cell death. Anticancer mechanistic studies also indicated that dietary components could display the ability to reverse epigenetic deregulation in assorted tumors via reverting the adverse epigenetic regulation, including alternation of DNA methylation and histone modification, and modulation of microRNA expression. Therefore, dietary components as therapeutic agents on epigenetics becomes an attractive approach for cancer prevention and intervention at the moment. In this review, we summarize the recent discoveries and underlying mechanisms of the most common dietary components for cancer prevention via epigenetic regulation. PMID- 26872813 TI - M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis. AB - Cisplatin-induced nephrotoxicity leaded to apoptosis of tubular epithelial cells (ECs) and tubulointerstitial fibrosis through ROS stress and inflammatory cytokines. Tubulointerstitial fibrosis caused by cisplatin might be via activation of resident fibroblasts and epithelial-mesenchymal transition (EMT) of tubular ECs. Inflammatory niche was crucial for progression of fibroblast activation or EMT. It had been reported that M1/M2 macrophage polarization regulated pro-inflammation or pro-resolving phase in damage repairing. However, the role of macrophage polarization on cisplatin-induced EMT of tubular ECs had not been well elucidated. In this study, we used co-cultured cell model and condition medium to examine the interaction between tubular ECs, fibroblasts and M1/M2 macrophages. Our data showed that cisplatin alone induced incomplete EMT of tubular ECs, whereas fibroblasts co-cultured with cisplatin-treated ECs could lead to fibroblast activation by detection of alpha-SMA and collagen-1. Moreover, decrease of iNOS and increase of argenase-1 and CD206 expression indicated that macrophages co-cultured with cisplatin-treated ECs would turn to M2 phenotype. Finally, we found that condition medium of M2 macrophages could promote complete EMT of cisplatin-treated ECs. Taken together, cisplatin created an inflammatory niche via tubular ECs to activate fibroblasts and stimulated M2 macrophage polarization. M2 macrophages could turn back to promote EMT of cisplatin-treated ECs. These results revealed the cooperative roles of tubular ECs, fibroblast and M2 macrophages to facilitate the progression of renal fibroblasis. PMID- 26872814 TI - Solitary renal metastasis of esophageal squamous cell carcinoma mimicking primary renal neoplasm - A case report and literature review. AB - Solitary renal metastasis of esophageal cancer is rare clinically, with only 14 cases being reported in the literature. The authors here report a case of a 53 year-old man with a metachronous hypopharyngeal and esophageal squamous cell carcinoma who developed a solitary renal metastasis after complete chemoradiotherapy for esophageal cancer, and subsequently received a left nephrectomy. The metastatic esophageal cancer was indistinguishable from primary renal neoplasm in the computed tomography but showed the histopathologic characteristic of esophageal cancer in directly invading the renal artery, and the tumor spreading in the kidney. The patient died of pneumonia two months after diagnosis. Among the previous 14 reported cases, 12 occurred in Asians, and their overall survival time ranges from two months to nine years after nephrectomy, either with or without adjuvant chemotherapy. Accordingly, a solitary renal mass in patients with a history of esophageal cancer is warranted to differentiate metastatic esophageal cancer from primary renal neoplasm, and a reliable therapy needs to be planned early for improving the patient's chance of survival. PMID- 26872815 TI - Approach to Optimize Anti-TNF-alpha Therapy in Patients With IBD. AB - OPINION STATEMENT: Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine that plays a major role during the initiation and perpetuation of inflammatory bowel disease (IBD). Anti-TNF-alpha agents are the most widely used biologics that specifically target either or both circulating and membrane-bound TNF-alpha, thus preventing its pro-inflammatory activity. Despite their efficacy, one third of the patients receiving anti-TNF-alpha agents are primary non responders and nearly half of the patients that initially respond may subsequently lose response (secondary loss of response). Many of these cases can be explained by immunogenicity, which can lead to lower drug levels associated with reduced response and serious adverse effects that cause patients to withdraw from treatment. New treatment algorithms instruct practitioners to check drug and antibody levels when there is loss of response, and then provide guidance towards either dose optimization and/or change in the biologic agent or class to help regain efficacy. PMID- 26872816 TI - Unsuccessful Detection of Plant MicroRNAs in Beer, Extra Virgin Olive Oil and Human Plasma After an Acute Ingestion of Extra Virgin Olive Oil. AB - The recent description of the presence of exogenous plant microRNAs from rice in human plasma had profound implications for the interpretation of microRNAs function in human health. If validated, these results suggest that food should not be considered only as a macronutrient and micronutrient supplier but it could also be a way of genomic interchange between kingdoms. Subsequently, several studies have tried to replicate these results in rice and other plant foods and most of them have failed to find plant microRNAs in human plasma. In this scenario, we aimed to detect plant microRNAs in beer and extra virgin olive oil (EVOO)--two plant-derived liquid products frequently consumed in Spain--as well as in human plasma after an acute ingestion of EVOO. Our hypothesis was that microRNAs present in beer and EVOO raw material could survive manufacturing processes, be part of these liquid products, be absorbed by human gut and circulate in human plasma. To test this hypothesis, we first optimized the microRNA extraction protocol to extract microRNAs from beer and EVOO, and then tried to detect microRNAs in those samples and in plasma samples of healthy volunteers after an acute ingestion of EVOO. PMID- 26872817 TI - Concomitant presence of Aspergillus fumigatus and Stenotrophomonas maltophilia in the respiratory tract: a new risk for patients with liver disease? AB - Concomitant lung colonization by Aspergillus fumigatus and Stenotrophomonas maltophilia was reported mainly in patients with cystic fibrosis (CF) and immunocompromised patients. The aim of the study was to assess the frequency of co-culture of A. fumigatus and S. maltophilia in respiratory samples of hospitalized patients, and to determine its associated factors. Between 2007 and 2011, all patients who had A. fumigatus in their respiratory samples were retrospectively enrolled in the study. Their clinical and laboratory data, including the presence of S. maltophilia in a respiratory sample, were collected within the same month. Of the 257 enrolled patients (372 respiratory samples), 71 % were immunocompromised and 32 % had chronic respiratory disease. S. maltophilia was isolated within the same month in 20 patients (7.8 %). In the univariate analysis, factors associated with concomitant culture of A. fumigatus and S. maltophilia were liver disease (P = 0.009), orotracheal intubation (P = 0.001), ventilator-associated pneumonia (P = 0.006), central venous catheter (P = 0.003), parenteral nutrition (P = 0.008) and culture of Pseudomonas aeruginosa in respiratory samples (P = 0.002). In the multivariate analysis, the simultaneous presence of P. aeruginosa in the respiratory tract (odds ratio (OR) = 3.19, 95 % confidence interval (CI) 1.11-9.14, P = 0.031), liver disease (OR = 3.92, 95 % CI 1.32-11.62, P = 0.014) and orotracheal intubation (OR = 3.42, 95 % CI 1.17-9.96, P = 0.024) were independently associated with the co-culture of S. maltophilia and A. fumigatus. Factors independently associated with the concomitant culture of A. fumigatus and S. maltophilia were identified. These results support a future prospective study focusing on liver disease and its complications. PMID- 26872819 TI - From gene polymorphisms to serum cytokine levels in irritable bowel syndrome. PMID- 26872818 TI - The Impact of the Fourth Edition of the WHO Classification of Lung Tumours on Histological Classification of Resected Pulmonary NSCCs. AB - INTRODUCTION: Histopathological classification of lung cancer is of central importance in the diagnostic routine, and it guides therapy in most patients. The fourth edition of the World Health Organization (WHO) Classification of Lung Tumours was recently published and includes changes to the diagnostic procedure for non-small cell carcinomas (NSCCs), with more emphasis on immunohistochemical (IHC) staining. METHODS: A total of 656 unselective cases of resected pulmonary NSCC were diagnosed according to the 2004 WHO classification. After IHC staining with cytokeratin 5, p40, p63, thyroid transcription factor 1 (clones 8G7G3/1 and SPT24), and napsin A, the diagnoses were revised in accordance with the new fourth edition of the WHO classification. RESULTS: Reclassification led to a new histological annotation in 36 of the 656 cases (5%). Most notable was the decrease in cases previously classified as large cell carcinomas (56 versus 12 cases). This was partially due to the exclusion of 21 neuroendocrine tumors from this group, with 20 cases ascribed to the adenocarcinoma group on the basis of IHC markers. Only seven cases of adenocarcinoma or squamous cell carcinoma were reclassified after the addition of IHC staining. There was a substantial overlap in staining properties between different markers of squamous and adenocarcinomatous differentiation, respectively, but in 17 to 31 cases (3%-5%), the diagnosis depended on the choice of markers. CONCLUSIONS: The fourth edition of the WHO Classification of Lung Tumours leads to changes in histological type in 5% of resected NSCCs. The incorporation of IHC staining into NSCC diagnostics demands awareness that the choice of ancillary stains has an effect on diagnosis. PMID- 26872820 TI - Disruptive Innovation: Implementation of Electronic Consultations in a Veterans Affairs Health Care System. AB - BACKGROUND: Electronic consultations (e-consults) offer rapid access to specialist input without the need for a patient visit. E-consult implementation began in 2011 at VA Boston Healthcare System (VABHS). By early 2013, e-consults were available for all clinical services. In this implementation, the requesting clinician selects the desired consultation within the electronic health record (EHR) ordering menu, which creates an electronic form that is pre-populated with patient demographic information and allows free-text entry of the reason for consult. This triggers a message to the requesting clinician and requested specialty, thereby enabling bidirectional clinician-clinician communication. OBJECTIVE: The aim of this study is to examine the utilization of e-consults in a large Veterans Affairs (VA) health care system. METHODS: Data from the electronic health record was used to measure frequency of e-consult use by provider type (physician or nurse practitioner (NP) and/or physician assistant), and by the requesting and responding specialty from January 2012 to December 2013. We conducted chart reviews for a purposive sample of e-consults and semi-structured interviews with a purposive sample of clinicians and hospital leaders to better characterize the process, challenges, and usability of e-consults. RESULTS: A total of 7097 e-consults were identified, 1998 from 2012 and 5099 from 2013. More than one quarter (27.56%, 1956/7097) of the e-consult requests originated from VA facilities in New England other than VABHS and were excluded from subsequent analysis. Within the VABHS e-consults (72.44%, 5141/7097), variability in frequency and use of e-consults across provider types and specialties was found. A total of 64 NPs requested 2407 e-consults (median 12.5, range 1-415). In contrast, 448 physicians (including residents and fellows) requested 2349 e consults (median 2, range 1-116). More than one third (37.35%, 1920/5141) of e consults were sent from primary care to specialists. While most e-consults reflected a request for specialist input to a generalist's question in diagnosis or management in the ambulatory setting, we identified creative uses of e consults, including requests for face-to-face appointments and documentation of pre-operative chart reviews; moreover, 7.00% (360/5141) of the e-consults originated from our sub-acute and chronic care inpatient units. In interviews, requesting providers reported high utility and usability. Specialists recognized the value of e-consults but expressed concerns about additional workload. CONCLUSIONS: The e-consult mechanism is frequently utilized for its initial intended purpose. It has also been adopted for unexpected clinical and administrative uses, developing into a "disruptive innovation" and highlighting existing gaps in mechanisms for provider communication. Further investigation is needed to characterize optimal utilization of e-consults within specialty and the medical center, and what features of the e-consult program, other than volume, represent valid measures of access and quality care. PMID- 26872822 TI - Quantitative Analysis of Carbon Steel with Multi-Line Internal Standard Calibration Method Using Laser-Induced Breakdown Spectroscopy. AB - A multi-line internal standard calibration method is proposed for the quantitative analysis of carbon steel using laser-induced breakdown spectroscopy (LIBS). A procedure based on the method was adopted to select the best calibration curves and the corresponding emission lines pairs automatically. Laser-induced breakdown spectroscopy experiments with carbon steel samples were performed, and C, Cr, and Mn were analyzed via the proposed method. Calibration curves of these elements were constructed via a traditional single line internal standard calibration method and a multi-line internal standard calibration method. The calibration curves obtained were evaluated with the determination coefficient, the root mean square error of cross-validation, and the average relative error of cross-validation. All of the parameters were improved significantly with the proposed method. The results show that accurate and stable calibration curves can be obtained efficiently via the multi-line internal standard calibration method. PMID- 26872823 TI - Combining Laser-Induced Breakdown Spectroscopy with Molecular Laser-Induced Fluorescence. AB - We propose combining laser-induced breakdown spectroscopy (LIBS) with molecular laser-induced fluorescence (MLIF) with resulting plasma-borne molecules as a means of studying laser-induced plasma (LIP). Examples of this method with LIP created Al, Si, and B monoxides are presented. Applicability of the LIBS-MLIF method for elemental and isotope analysis is demonstrated. PMID- 26872821 TI - Large genomic differences between Moraxella bovoculi isolates acquired from the eyes of cattle with infectious bovine keratoconjunctivitis versus the deep nasopharynx of asymptomatic cattle. AB - Moraxella bovoculi is a recently described bacterium that is associated with infectious bovine keratoconjunctivitis (IBK) or "pinkeye" in cattle. In this study, closed circularized genomes were generated for seven M. bovoculi isolates: three that originated from the eyes of clinical IBK bovine cases and four from the deep nasopharynx of asymptomatic cattle. Isolates that originated from the eyes of IBK cases profoundly differed from those that originated from the nasopharynx of asymptomatic cattle in genome structure, gene content and polymorphism diversity and consequently placed into two distinct phylogenetic groups. These results suggest that there are genetically distinct strains of M. bovoculi that may not associate with IBK. PMID- 26872824 TI - Using a mHealth tutorial application to change knowledge and attitude of frontline health workers to Ebola virus disease in Nigeria: a before-and-after study. AB - BACKGROUND: The Ebola epidemic exposed the weak state of health systems in West Africa and their devastating effect on frontline health workers and the health of populations. Fortunately, recent reviews of mobile technology demonstrate that mHealth innovations can help alleviate some health system constraints such as balancing multiple priorities, lack of appropriate tools to provide services and collect data, and limited access to training in health fields such as mother and child health, HIV/AIDS and sexual and reproductive health. However, there is little empirical evidence of mHealth improving health system functions during the Ebola epidemic in West Africa. METHODS: We conducted quantitative cross-sectional surveys in 14 health facilities in Ondo State, Nigeria, to assess the effect of using a tablet computer tutorial application for changing the knowledge and attitude of health workers regarding Ebola virus disease. RESULTS: Of 203 participants who completed pre- and post-intervention surveys, 185 people (or 91%) were female, 94 participants (or 46.3%) were community health officers, 26 people (13 %) were nurses/midwives, 8 people (or 4%) were laboratory scientists and 75 people (37%) belonged to a group called others. Regarding knowledge of Ebola: 178 participants (or 87.7%) had foreknowledge of Ebola before the study. Further analysis showed an 11% improvement in average knowledge levels between pre- and post-intervention scores with statistically significant differences (P < 0.05) recorded for questions concerning the transmission of the Ebola virus among humans, common symptoms of Ebola fever and whether Ebola fever was preventable. Additionally, there was reinforcement of positive attitudes of avoiding the following: contact with Ebola patients, eating bush meat and risky burial practices as indicated by increases between pre- and post-intervention scores from 83 to 92%, 57 to 64% and 67 to 79%, respectively. Moreover, more participants (from 95 to 97%) reported a willingness to practice frequent hand washing and disinfecting surfaces and equipment following the intervention, and more health workers were willing (from 94 to 97%) to use personal protective equipment to prevent the transmission of Ebola. CONCLUSIONS: The modest improvements in knowledge and reported attitudinal change toward Ebola virus disease suggests mHealth tutorial applications could hold promise for training health workers and building resilient health systems to respond to epidemics in West Africa. PMID- 26872825 TI - Editorial: Innovative Methods and Advancement in Current HIV/AIDS Research. PMID- 26872826 TI - Acute intermittent porphyria precipitated by atazanavir/ritonavir. AB - Porphyrias are a group of metabolic disorders that are relatively uncommon and underdiagnosed. Although the association between HIV infection and antiretrovirals with porphyria cutanea tarda is well established, there are fewer data linking HIV and the acute hepatic porphyrias. We report the first case of acute intermittent porphyria precipitated by the drugs atazanavir and ritonavir, presenting with unexplained abdominal pain. PMID- 26872827 TI - Genome-wide studies reveal novel and distinct biological pathways regulated by SIN3 isoforms. AB - BACKGROUND: The multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, a single Sin3A gene encodes different isoforms of SIN3, of which SIN3 187 and SIN3 220 are the major isoforms. Previous studies have demonstrated functional non-redundancy of SIN3 isoforms. The role of SIN3 isoforms in regulating distinct biological processes, however, is not well characterized. RESULTS: We established a Drosophila S2 cell culture model system in which cells predominantly express either SIN3 187 or SIN3 220. To identify genomic targets of SIN3 isoforms, we performed chromatin immunoprecipitation followed by deep sequencing. Our data demonstrate that upon overexpression of SIN3 187, the level of SIN3 220 decreased and the large majority of genomic sites bound by SIN3 220 were instead bound by SIN3 187. We used RNA-seq to identify genes regulated by the expression of one isoform or the other. In S2 cells, which predominantly express SIN3 220, we found that SIN3 220 directly regulates genes involved in metabolism and cell proliferation. We also determined that SIN3 187 regulates a unique set of genes and likely modulates expression of many genes also regulated by SIN3 220. Interestingly, biological pathways enriched for genes specifically regulated by SIN3 187 strongly suggest that this isoform plays an important role during the transition from the embryonic to the larval stage of development. CONCLUSION: These data establish the role of SIN3 isoforms in regulating distinct biological processes. This study substantially contributes to our understanding of the complexity of gene regulation by SIN3. PMID- 26872828 TI - Immediate effect of vibratory stimuli on quadriceps function in healthy adults. AB - INTRODUCTION: The purpose of this study was to compare the effect of whole body vibration (WBV) and local muscle vibration (LMV) on quadriceps function. METHODS: Sixty adults were randomized to WBV, LMV, or control groups. Quadriceps function [Hoffmann (H)-reflex, active motor threshold (AMT), motor evoked potential (MEP) and electromyographic amplitude, peak torque (PT), rate of torque development (RTD), and central activation ratio (CAR)] was assessed before and immediately after and 10 and 20 minutes after interventions. RESULTS: WBV improved PT, CAR, AMT, EMG, and MEP amplitude, and EMG amplitude and CAR were greater than control after application. LMV improved EMG amplitude and AMT, and EMG amplitude was greater than control after application. AMT remained lower 10 and 20 minutes after WBV and LMV. No differences were noted between LMV and WBV. Vibration did not influence H-reflex or RTD. CONCLUSIONS: WBV and LMV increased quadriceps function and may be used to enhance the efficacy of strengthening protocols. Muscle Nerve 54: 469-478, 2016. PMID- 26872829 TI - Traumatic manual enucleation (gouging) from assault. PMID- 26872830 TI - Rasmussen number greater than one. AB - This essay describes the ramifying influence of Jens Rasmussen, illustrating how his work lives on through people whom he has influenced, even though they may have never directly collaborated. I approach this in three ways: a social network analysis of the 'Rasmussen number' (an analogue of the Erdos number); and two citations network analyses based on different search domains and different network structures. PMID- 26872831 TI - Perinatal vitamin D levels are not associated with later risk of developing pediatric-onset inflammatory bowel disease: a Danish case-cohort study. AB - Objective Basic and epidemiologic studies on inflammatory bowel disease (IBD) have suggested an association between vitamin D and IBD risk. Though, the literature on IBD - especially pediatric-onset IBD - and vitamin D is still in its cradle. We therefore wanted to examine if levels of 25(OH)D at birth were associated with increased risk of developing pediatric-onset IBD. Material and methods A case-cohort study composed of cases diagnosed with Crohn's disease, ulcerative colitis or indeterminate/unclassified colitis and healthy controls. Cases and controls were matched on date of birth and were born in the period 1981 2004. Cases were diagnosed before the age of 18 years. The concentration of 25(OH)D was assessed from neonatal dried blood spots using a highly sensitive liquid chromatography tandem mass spectrometry. Odds ratios (OR) were calculated using conditional logistic regression and two-way ANOVA were used to test for season and birth year 25(OH)D variations. A total of 384 matched pairs were included in the statistical analyses. Results No significant association were found between levels of 25(OH)D and IBD risk in the adjusted model (OR [95% CI] (per 25 nmol/L increase), 1.12 [0.88; 1.42], p = 0.35). 25(OH)D levels were found to fluctuate significantly with season (p < 0.001) and year (p < 0.001). Median/Q1-Q3 values for 25(OH)D were 27.1/16.5-39.5 nmol/L for cases and 25.7/16.1-39.4 nmol/L for controls. Conclusion Our study do not suggest that a window of vulnerability exist around time of birth in regards to 25(OH)D levels and later pediatric-onset IBD risk. PMID- 26872832 TI - Haspin has Multiple Functions in the Plant Cell Division Regulatory Network. AB - Progression of cell division is controlled by various mitotic kinases. In animal cells, phosphorylation of histone H3 at Thr3 by the kinase Haspin (haploid germ cell-specific nuclear protein kinase) promotes centromeric Aurora B localization to regulate chromosome segregation. However, less is known about the function of Haspin in regulatory networks in plant cells. Here, we show that inhibition of Haspin with 5-iodotubercidin (5-ITu) in Bright Yellow-2 (BY-2) cells delayed chromosome alignment. Haspin inhibition also prevented the centromeric localization of Aurora3 kinase (AUR3) and disrupted its function. This suggested that Haspin plays a role in the specific positioning of AUR3 on chromosomes in plant cells, a function conserved in animals. The results also indicated that Haspin and AUR3 are involved in the same pathway, which regulates chromosome alignment during prometaphase/metaphase. Remarkably, Haspin inhibition by 5-ITu also led to a severe cytokinesis defect, resulting in binuclear cells with a partially formed cell plate. The 5-ITu treatment did not affect microtubules, AUR1/2 or the NACK-PQR pathway; however, it did alter the distribution of actin filaments on the cell plate. Together, these results suggested that Haspin has several functions in regulating cell division in plant cells: in the localization of AUR3 on centromeres and in regulating late cell plate expansion during cytokinesis. PMID- 26872833 TI - A Feed-Forward Loop Consisting of the Response Regulator RpaB and the Small RNA PsrR1 Controls Light Acclimation of Photosystem I Gene Expression in the Cyanobacterium Synechocystis sp. PCC 6803. AB - Since cyanobacteria need to decrease PSI content to avoid absorption of excess light energy, down-regulation of PSI gene expression is one of the key characteristics of the high-light (HL) acclimation response. The transcriptional regulator RpaB and the small RNA PsrR1 (photosynthesis regulatory RNA1) have been suggested to be the two most critical factors for this response in Synechocystis sp. PCC 6803. In this study, we found that the HLR1 DNA-binding motif, the recognition sequence for RpaB, is highly conserved in the core promoter region of the psrR1 gene among cyanobacterial species. Gel mobility shift assay revealed that RpaB binds to the HLR1 sequence of psrR1 in vitro. RNA gel blot analysis together with chromatin affinity purification (ChAP) analysis suggested that PSI genes are activated and the psrR1 gene is repressed by the binding of RpaB under low-light (LL) conditions. A decrease in DNA binding affinity of RpaB occurs within 5 min after the shift from LL to HL conditions, leading to the prompt decrease in PSI promoter activity together with derepression of psrR1 gene expression. Accumulating PsrR1 molecules then prevent translation from pre existing PSI transcripts. By this dual repression at transcriptional and post transcriptional levels, rapid and strict down-regulation of PSI expression under HL is secured. Our findings suggest that RpaB and PsrR1 constitute a feed-forward loop for the regulation of PSI gene expression to achieve a rapid acclimation response to the damaging HL conditions. PMID- 26872834 TI - OsCOL10, a CONSTANS-Like Gene, Functions as a Flowering Time Repressor Downstream of Ghd7 in Rice. AB - Flowering time, or heading date, is a critical agronomic trait that determines the cropping season and regional adaptability, and ultimately grain yield in rice. A number of genes involved in photoperiodic flowering have been cloned and their roles in modulating expression of the flowering genes have been characterized to a certain extent. However, much less is known about the pathway in transmitting the day length response signal(s) to induce transition to reproductive growth. Here, we report a constitutive flowering repressor OsCOL10, which encodes a member of the CONSTANS-like (COL) family. Transgenic rice plants overexpressing OsCOL10 (driven by a strong promoter or by fusing it to the activation domain of VP64) showed delayed flowering time under both short and long days.OsCOL10 is affected by the circadian clock and is preferentially expressed in leaf mesophyll cells; it is localized to the nucleus and has transcriptional activation activity. Further studies show that OsCOL10 represses the expression of theFT-like genes RFT1 and Hd3a through Ehd1. Transcripts of OsCOL10 are more abundant in plants carrying a functional Ghd7 allele or overexpressing Ghd7 than in Ghd7-deficient plants, thus placing OsCOL10 downstream of Ghd7.Taking these findings together, we conclude that OsCOL10 functions as a flowering time repressor that links Ghd7 and Ehd1 in rice. PMID- 26872835 TI - Genome-Wide Identification, Evolution and Functional Divergence of MYB Transcription Factors in Chinese White Pear (Pyrus bretschneideri). AB - The MYB superfamily is large and functionally diverse in plants. To date, MYB family genes have not yet been identified in Chinese white pear (Pyrus bretschneideri), and their functions remain unclear. In this study, we identified 231 genes as candidate MYB genes and divided them into four subfamilies. The R2R3 MYB (PbrMYB) family shared an R2R3 domain with 104 amino acid residues, including five conserved tryptophan residues. The Pbr MYB family was divided into 37 functional subgroups including 33 subgroups which contained both MYB genes of Rosaceae plants and AtMYB genes, and four subgroups which included only Rosaceae MYB genes or AtMYB genes. PbrMYB genes with similar functions clustered into the same subgroup, indicating functional conservation. We also found that whole genome duplication (WGD) and dispersed duplications played critical roles in the expansion of the MYB family. The 87 Pbr MYB duplicated gene pairs dated back to the two WGD events. Purifying selection was the primary force driving Pbr MYB gene evolution. The 15 gene pairs presented 1-7 codon sites under positive selection. A total of 147 expressed genes were identified from RNA-sequencing data of fruit, and six Pbr MYB members in subgroup C1 were identified as important candidate genes in the regulation of lignin synthesis by quantitative real-time PCR analysis. Further correlation analysis revealed that six PbrMYBs were significantly correlated with five structural gene families (F5H, HCT, CCR, POD and C3'H) in the lignin pathway. The phylogenetic, evolution and expression analyses of the MYB gene family in Chinese white pear establish a solid foundation for future comprehensive functional analysis of Pbr MYB genes. PMID- 26872836 TI - Functional Analysis of a MATE Gene OsFRDL2 Revealed its Involvement in Al-Induced Secretion of Citrate, but a Lower Contribution to Al Tolerance in Rice. AB - The multidrug and toxic compound extrusion (MATE) transporters represent a large transporter family in plants, but the role of most genes in this family has not been examined. We functionally characterized a MATE family member, OsFRDL2, in rice (Oryza sativa). OsFRDL2 showed an efflux transport activity for citrate when it was expressed in both Xenopus oocytes and cultured tobacco cells. OsFRDL2 was mainly expressed in the roots and its expression was not induced by iron (Fe) deficiency, but it was rapidly up-regulated by aluminum (Al). Furthermore, the expression of OsFRDL2 was regulated by ART1, a C2H2-type zinc-finger transcription factor for Al tolerance. OsFRDL2 protein was localized at unidentified vesicles in the cytosol, but not co-localized with either mitochondria or peroxisomes when expressed in both onion epidermal cells and cultured tobacco cells. Knockout of OsFRDL2 decreased Al-induced secretion of citrate from the roots, but did not affect the internal citrate concentration. The Al-induced inhibition of root elongation was similar between the OsFRDL2 knockout line and its wild-type rice. Knockout of OsFRDL2 did not affect the translocation of Fe from the roots to the shoots. A double mutant between osfrdl2 and osfrdl4 or osfrdl1 did not further decrease the Al-induced citrate secretion and Fe translocation compared with the single mutant. Collectively, our results indicate that although OsFRDL2 is involved in the Al-induced secretion of citrate, its contribution to high Al tolerance is relatively small in rice. PMID- 26872837 TI - Redox-Dependent Conformational Dynamics of Decameric 2-Cysteine Peroxiredoxin and its Interaction with Cyclophilin 20-3. AB - 2-Cysteine peroxiredoxins (2-CysPrxs) switch between functions as a thiol peroxidase, chaperone, an interaction partner and possibly a proximity-based oxidase in a redox-dependent manner. In photosynthetic eukaryotes, 2-CysPrx localizes to the plastid, functions in the context of photosynthesis and enables an ascorbate peroxidase-independent water-water cycle for detoxifying H2O2 The high degree of evolutionary conservation of 2-CysPrx suggests that the switching is an essential characteristic and needed to transduce redox information to downstream pathways and regulation. The study aimed at exploring the dissociation behavior of 2-CysPrx and its interactions with cyclophilin depending on bulk phase conditions. Isothermal titration microcalorimetry (ITC), dynamic light scattering and size exclusion chromatography (SEC) proved the previously suggested model that reduced 2-CysPrx below a critical transition concentration (CTC) exists in its dimeric state, and above the CTC adopts the decameric state. The presence of cyclophilin 20-3 (Cyp20-3) affected the CTC of a 2-CysPrx decamer suggesting interaction which was further quantified by direct titration of 2 CysPrx with Cyp20-3, and in overlays. Finally catalytic inactivation assays showed the higher catalytic efficiency of 2-CysPrx at pH 8 compared with pH 7.2, but also revealed increased inactivation by hyperoxidation at pH 8. Interestingly, calculation of the average turnover number until inactivation gave rather similar values of 243 and 268 catalytic cycles at pH 8 and pH 7.2, respectively. These quantitative data support a model where 2-CysPrx and Cyp20-3, by interaction, form a redox-sensitive regulatory module in the chloroplast which is under control of the photosynthesis-linked stromal pH value, the redox state and additional stromal protein factor(s). PMID- 26872838 TI - A Transcription Factor gammaMYB1 Binds to the P1BS cis-Element and Activates PLA2 gamma Expression with its Co-Activator gammaMYB2. AB - Phospholipase A2(PLA2) hydrolyzes phospholipid molecules to produce two products that are both precursors of second messengers of signaling pathways and signaling molecules per se.Arabidopsis thaliana PLA2 paralogs (-beta,-gamma and -delta) play critical roles during pollen development, pollen germination and tube growth. In this study, analysis of the PLA2-gamma promoter using a deletion series revealed that the promoter region -153 to -1 is crucial for its pollen specificity. Using a yeast one-hybrid screening assay with the PLA2-gamma promoter and an Arabidopsis transcription factor (TF)-only library, we isolated two novel MYB-like TFs belonging to the MYB-CC family, denoted here as gammaMYB1 and gammaMYB2. By electrophoretic mobility shift assay, we found that these two TFs bind directly to the P1BS (phosphate starvation response 1-binding sequence)cis-element of the PLA2-gamma promoter. gammaMYB1 alone functioned as a transcriptional activator for PLA2-gamma expression, whereas gammaMYB2 directly interacted with gammaMYB1 and enhanced its activation. Overexpression of gammaMYB1 in the mature pollen grain led to increased expression of not only the PLA2-gamma gene but also of several genes whose promoters contain the P1BS cis element and which are involved in the Pi starvation response, phospholipid biosynthesis and sugar synthesis. Based on these results, we suggest that the TF gammaMYB1 binds to the P1BS cis-element, activates the expression of PLA2-gamma with the assistance of its co-activator, gammaMYB2, and regulates the expression of several target genes involved in many plant metabolic reactions. PMID- 26872839 TI - The Increasing Impact of Activity-Based Protein Profiling in Plant Science. AB - The active proteome dictates plant physiology. Yet, active proteins are difficult to predict based on transcript or protein levels, because protein activities are regulated post-translationally in their microenvironments. Over the past 10 years, activity-based protein profiling (ABPP) is increasingly used in plant science. ABPP monitors the activities of hundreds of plant proteins using tagged chemical probes that react with the active site of proteins in a mechanism dependent manner. Since labeling is covalent and irreversible, labeled proteins can be detected and identified on protein gels and by mass spectrometry using tagged fluorophores and/or biotin. Here, we discuss general concepts, approaches and practical considerations of ABPP, before we summarize the discoveries made using 40 validated probes representing 14 chemotypes that can monitor the active state of >4,500 plant proteins. These discoveries and new opportunities indicate that this emerging functional proteomic technology is a powerful discovery tool that will have an increasing impact on plant science. PMID- 26872840 TI - A multilevel analysis to explain self-reported adverse health effects and adaptation to urban heat: a cross-sectional survey in the deprived areas of 9 Canadian cities. AB - BACKGROUND: This study identifies the characteristics and perceptions related to the individual, the dwelling and the neighbourhood of residence associated with the prevalence of self-reported adverse health impacts and an adaptation index when it is very hot and humid in summer in the most disadvantaged sectors of the nine most populous cities of Quebec, Canada, in 2011. METHODS: The study uses a cross-sectional design and a stratified representative sample; 3485 people (individual-level) were interviewed in their residence. They lived in 1647 buildings (building-level) in 87 most materially and socially disadvantaged census dissemination areas (DA-level). Multilevel analysis was used to perform 3 level models nested one in the other to examine individual impacts as well as the adaptation index. RESULTS: For the prevalence of impacts, which is 46 %, the logistic model includes 13 individual-level indicators (including air conditioning and the adaptation index) and 1 building-level indicator. For the adaptation index, with values ranging from -3 to +3, the linear model has 10 individual-level indicators, 1 building-level indicator and 2 DA-level indicators. Of all these indicators, 9 were associated to the prevalence of impacts only and 8 to the adaptation index only. CONCLUSION: This 3-level analysis shows the differential importance of the characteristics of residents, buildings and their surroundings on self-reported adverse health impacts and on adaptation (other than air conditioning) under hot and humid summer conditions. It also identifies indicators specific to impacts or adaptation. People with negative health impacts from heat rely more on adaptation strategies while low physical activity and good dwelling/building insulation lead to lower adaptation. Better neighbourhood walkability favors adaptations other than air conditioning. Thus, adaptation to heat in these neighbourhoods seems reactive rather than preventive. These first multi-level insights pave the way for the development of a theoretical framework of the process from heat exposure to impacts and adaptation for research, surveillance and public health interventions at all relevant levels. PMID- 26872841 TI - The Relationship between Intolerance of Uncertainty and Anxiety in Men on Active Surveillance for Prostate Cancer. AB - PURPOSE: Anxiety may serve as a major barrier to participation in active surveillance. Intolerance of uncertainty, that is the tendency to perceive the potential for negative events as threatening, has been linked to cancer related worry. Accordingly we explored prospectively the relationship of intolerance of uncertainty with anxiety along with other clinical factors among men treated with active surveillance for prostate cancer. MATERIALS AND METHODS: A total of 119 men with D'Amico low risk prostate cancer participating in active surveillance completed the HADS (Hospital Anxiety and Depression Scale), MAX-PC (Memorial Anxiety Scale for Prostate Cancer), IUS (Intolerance of Uncertainty Scale) and I PSS (International Prostate Symptom Score) surveys from 2011 to 2014. We evaluated the relationship between anxiety and IUS score after adjusting for patient characteristics, cancer information and I-PSS using bivariable and multivariable analyses. RESULTS: Of the men 18 (15.1%) and 17 (14.3%) reported clinically significant anxiety on the generalized and prostate cancer specific scales, respectively. On bivariable analysis men with moderate/severe urinary symptoms and higher IUS scores reported more generalized and prostate cancer specific anxiety than men with mild urinary symptoms and lower IUS scores, respectively (p <=0.008). Men with depressive symptoms (p = 0.024) or a family history of prostate cancer (p = 0.006) experienced greater generalized anxiety. On multivariable analysis IUS score was significantly associated with generalized and prostate cancer specific anxiety (OR 1.22, 95% CI 1.09-1.38 and OR 1.29, 95% CI 1.13-1.49, respectively) while moderate/severe urinary symptoms were associated with prostate cancer specific anxiety (OR 6.89, 95% CI 1.33-35.68). CONCLUSIONS: Intolerance of uncertainty and urinary symptoms may promote anxiety in men on active surveillance for prostate cancer. Patient education, management of lower urinary tract symptoms and behavioral interventions may lessen anxiety related to uncertainty intolerance and help maintain patient engagement in active surveillance. PMID- 26872842 TI - Patterns of Care for Newly Diagnosed Benign Prostatic Hyperplasia in the United States. AB - PURPOSE: We examined diagnostic tests and treatment patterns in men with new onset benign prostatic hyperplasia using consolidated national electronic health record data. MATERIALS AND METHODS: The Humedica(r) electronic health record database consists of de-identified patient records from approximately 25 million patients in the United States. Using this database, men with a new benign prostatic hyperplasia diagnosis (benign prostatic hyperplasia, bladder neck obstruction, urinary retention and incomplete bladder emptying) between July 1, 2009 and June 30, 2012 were included in study. Exclusion criteria included conditions such as genitourinary cancers, radiation cystitis, neurogenic bladder and urological pain diagnoses. Diagnostic tests and treatments were summarized and stratified by age (less than 65 vs 65 years or greater) and serum prostate specific antigen level. RESULTS: A total of 38,252 men met inclusion criteria. Mean followup was 1,020 days. Serum creatinine in 92% of patients, serum prostate specific antigen in 76% and urinalysis in 52% were the most common tests. Invasive testing was obtained in less than 20% of patients. Treatments included watchful waiting in 40% of patients, pharmacological therapy in 59.4% and surgery in 2.2%. alpha-Blockers were prescribed in 50.7% of men. Men older than 65 years and with higher prostate specific antigen levels were less likely to be treated with watchful waiting. Therapy with a 5-ARI (5-alpha reductase inhibitor) was prescribed in 23% to 29% of men across all prostate specific antigen categories. CONCLUSIONS: The majority of clinical care for new onset benign prostatic hyperplasia was in concordance with guideline recommendations. Based on prostate specific antigen values, 5-ARI therapy was underutilized in men with large prostates and was over utilized in men with small prostates. PMID- 26872843 TI - An unusual case of atrial fibrillation. PMID- 26872844 TI - LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease. AB - To fulfill their multiple roles in organ development and adult tissue homeostasis, hedgehog (HH) morphogens act through their receptor Patched (PTCH) on target cells. However, HH actions also require HH binding proteins, auxiliary cell surface receptors that agonize or antagonize morphogen signaling in a context-dependent manner. Here, we discuss recent findings on the LDL receptor related protein 2 (LRP2), an exemplary HH binding protein that modulates sonic hedgehog activities in stem and progenitor cell niches in embryonic and adult tissues. LRP2 functions are crucial for developmental processes in a number of tissues, including the brain, the eye, and the heart, and defects in this receptor pathway are the cause of devastating congenital diseases in humans. Developmental Dynamics 245:569-579, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26872845 TI - The neurodevelopment of social buffering and fear learning: integration and crosstalk. PMID- 26872847 TI - Studying ritual and individual orientations to alcohol use: Drinking motives and their connection to intoxication in Finland in the 2000s. AB - BACKGROUND: Finland was an agricultural country until the 1960s. Thereafter, Finland modernized rapidly. Studies have postulated that as Finland becomes modernized, intoxication-oriented drinking would gradually decrease. Current studies, however, show that heavy episodic drinking has lately become more common among men and women. Simultaneously, drinking is seldom motivated by the purpose of getting drunk. The article tackles this conundrum by approaching drinking motives from a ritual and an individual perspective. We study what kinds of drinking motives currently exist in Finland, their prevalence among different population groups, how they vary by social background, and their association with intoxication. METHODS: The data were collected as part of the nationally representative Drinking Habit Survey in 2008. It consists of verbal descriptions on the most recent drinking occasion (N=521), estimations of its blood alcohol content, and responses to pre-defined standardized motive questions related to the latest drinking occasions (N=8732). RESULTS: Besides the motive 'to get drunk', also the motives of drinking as a 'time-out' ritual, 'to get into the mood' and 'I drunk to brighten up' predict a "wet" drinking occasion. Overall, Finns highlight drinking motives of sociability, relaxation, meal drinking and situational factors. The more educated orientate to their drinking more with motives that express mastery of cultural capital and individuality. The less educated and the young, again, orientate to their drinking more with motives that imply intoxication and external expectations. CONCLUSIONS: Whereas the ritual perspective discloses what kinds of situations predict intoxication, the individual perspective reveals what kinds of individualistic orientations are associated with drunkenness. These perspectives partly speak past each other and are difficult to combine. The article proposes that situational perspective would serve as a bridge between them and enable the incorporation of results from different research traditions. PMID- 26872846 TI - Characterising dark net marketplace purchasers in a sample of regular psychostimulant users. AB - BACKGROUND: The past five years has seen a proliferation in marketplaces operating on the 'dark net' selling licit and illicit substances. While monitoring systems have investigated the specific substances for sale on these marketplaces, less is known about consumer motivations for accessing these marketplaces and factors associated with their use. METHODS: An Australian national sample (n=800) recruited on the basis of regular psychostimulant use was recruited and asked about purchasing substances from dark net marketplaces and the reasons for doing so. Respondents who had purchased any drug from a dark net marketplace in the preceding year were compared to those who had not in terms of demographic information and factors including drug use, criminal activity, and sexual and mental health. RESULTS: Nine percent (n=68) of the sample had purchased from dark net markets in the past year. MDMA, LSD and cannabis were the three most commonly purchased substances, and the main benefits cited for purchasing online were the better quality and lower cost of drugs available. Controlling for other factors, participants who purchased from dark net marketplaces in the past year tended to be younger, more likely to be involved in recent property crime and to have used more classes of drugs in the preceding six months, specifically psychedelics and 'new psychoactive drugs'. CONCLUSIONS: Though a small minority of participants reported having purchased drugs online in the preceding six months, these appeared to be a more 'entrenched' group of consumers, with more diverse substance use and rates of criminal activity. For consumers in the current sample reporting recent dark net usage, country borders are now less of a significant barrier to purchase and there is a wider range of substances available than ever before. PMID- 26872848 TI - Understanding client satisfaction with HIV testing and counseling services: a mixed-methods study in four African countries. AB - This paper uses mixed methods to provide comparative evidence across four African countries and identify those aspects of the testing experience that are the most important components of clients' satisfaction with services. We analyze data from three sources: a survey of clients at health facilities that included closed ended questions about specific services and interactions around testing; responses to open-ended questions about testing experiences that were part of the same survey; and semi-structured interviews with a subsample of respondents who described their experience of testing and being diagnosed with HIV. High levels of reported satisfaction are found in both the survey and interview. The critical factors contributing to client satisfaction included: the three C's of testing counseling, consent, and confidentiality, client-provider interactions, convenience of location, "good services", and reliable test results. PMID- 26872849 TI - The venous lymph node flap for the treatment of peripheral lymphedema: Preliminary evidence. PMID- 26872850 TI - Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia. AB - Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans. PMID- 26872851 TI - Role of contralesional hemisphere in paretic arm reaching in patients with severe arm paresis due to stroke: A preliminary report. AB - Stroke is highly prevalent and a leading cause of serious, long-term disability among American adults. Impaired movement (i.e. paresis) of the stroke-affected arm is a major contributor to post-stroke disability, yet the mechanisms of upper extremity motor recovery are poorly understood, particularly in severely impaired patients who lack hand function. To address this problem, we examined the functional relevance of the contralesional hemisphere in paretic arm motor performance in individuals with severe arm paresis. Twelve individuals with severe stroke-induced arm paresis (Upper Extremity Fugl-Meyer Assessment=17.1 +/- 8.5; maximum score=66) participated in the study. Participants performed a reaching response time task with their paretic arm. At varying time intervals following a 'Go' cue, a pair of transcranial magnetic stimulation (TMS) pulses were delivered to contralesional hemisphere primary motor (M1) or dorsal pre motor cortex (PMd) to momentarily disrupt the pattern of neural firing. Response time components and hand-path characteristics were compared across the 2 sites for trials with and without TMS disruption. There was no significant effect of TMS disruption on overall Response time or Reaction time, but Movement time was significantly longer (i.e. slower) with disruption of the contralesional hemisphere (p=0.015), regardless of which area was stimulated. Peak hand-path velocity and hand-path smoothness were also significantly lower (p=0.005 and p<0.0001, respectively) with TMS disruption of the contralesional hemisphere. The data from this study provide evidence supporting a functionally relevant role of contralesional hemisphere motor areas in paretic arm reaching movements in individuals with severe post-stroke arm impairment. PMID- 26872852 TI - Longitudinal study on modulated corticospinal excitability throughout recovery in supratentorial stroke. AB - Corticospinal excitability (CSE) is modulated by stroke-induced lesions affecting the brain. This modulation is known to be dependent on the timing of the evaluation, and strongest abnormalities are often found in the acute stage. Our study aimed to characterize changes in CSE asymmetry between the affected and the unaffected hemisphere (AH and UH) during the first month after stroke onset and at 6 month follow-up. Neuronavigated transcranial magnetic stimulation (nTMS) was used to assess the CSE of the abductor pollicis brevis (APB) muscle of the hand and tibialis anterior (TA) muscle of the leg in 16 patients over 5 time-points. AH excitability recovered significantly during 6 months, whereas interhemispheric asymmetry remained significant up to 1 month post-stroke in the APB muscle. Greater initial CSE was associated with good motor function at 6 months. The motor cortical excitatory recovery initiated within week of the stroke and was most prominent within 1 month after stroke onset. Lesion size correlated with CSE of the UH at 10 days, while overall severity of the symptoms correlated inversely with CSE of the AH. This study demonstrates the quick improvement in the CSE via estimation of interhemispheric asymmetry; however, the recovery in the asymmetry continues to normalize even after reaching the threshold for normal values in CSE. PMID- 26872853 TI - A conceptual framework for rationalized and standardized Universal Newborn Hearing Screening (UNHS) programs. AB - Congenital hearing loss is the most frequent birth defect. The American Academy of Pediatrics and the Joint Committee on Infant Hearing established quality of care process indicators for Universal Newborn Hearing Screening starting from 1999. In a previous systematic review of Universal Newborn Hearing Screening studies we highlighted substantial variability in program design and in reported performance data. In order to overcome these heterogeneous findings we think it is necessary to optimize the implementation of Universal Newborn Hearing Screening programs with an appropriate application of the planning, executing, and monitoring, verifications and reporting phases. For this reason we propose a conceptual framework that logically integrates these three phases and, consequently, a tool (a check-list) for their rationalization and standardization.Our paper intends to stimulate debate on how to ameliorate the routine application of high quality Universal Newborn Hearing Screening programs. The conceptual framework is proposed to optimize, rationalise and standardise their implementation. The checklist is intended to allow an inter-program comparison by removing heterogeneity in processes description and assessment. PMID- 26872854 TI - Linear epidermolytic ichthyosis: detection of granular degeneration with shrinking nuclei showing focal parakeratosis. PMID- 26872855 TI - Scoring systems for infantile hemangioma: the Hemangioma Activity Score versus the Hemangioma Activity and Severity Index. PMID- 26872856 TI - Freezing and non-freezing cold weather injuries: a systematic review. AB - INTRODUCTION: The debilitating impact of cold weather on the human body is one of the world's oldest recorded injuries. The severe and life-changing damage which can be caused is now more commonly seen recreationally in extreme outdoor sports rather than in occupational settings such as the military. The diagnosis and treatment of these injuries need to be completed carefully but quickly to reduce the risk of loss of limb and possibly life. Therefore, we have conducted a systematic review of the literature surrounding cold weather injuries (CWIs) to ascertain the epidemiology and current management strategies. SOURCES OF DATA: Medline (PubMED), EMBASE, CINHAL, Cochrane Collaboration Database, Web of Science, Scopus and Google Scholar. AREAS OF AGREEMENT IMMEDIATE FIELD TREATMENT: The risk of freeze thaw freeze injuries. Delayed surgical intervention when possible. Different epidemiology of freezing and non-freezing injuries. AREAS OF CONTROVERSY: Prophylatic use of antibiotics; the use of vasodilators surgical and medical. GROWING POINTS: The use of ilioprost and PFG2a for the treatment of deep frostbite. AREAS TIMELY FOR DEVELOPING RESEARCH: The treatment of non-freezing CWIs with their long-term follow-up. PMID- 26872858 TI - Ebola virus disease: emergence, outbreak and future directions. AB - BACKGROUND: The West African Ebola crisis of 2013-15 is the largest outbreak since Ebola was first identified; Ebola has high case fatality. SOURCES OF DATA: Pubmed with terms 'Ebola' and 'EVD' from January 1976 to June 2015. Public domain material. AREAS OF AGREEMENT: The emergence of Ebola virus, virology, clinical features and the major elements of the 2014 outbreak and the public health response. Ebola is only transmitted by direct contact with infected individuals (including dead bodies) and their body fluids. Methods of control in hospitals and burials, and protection of healthcare workers are well established if difficult to achieve. AREAS OF CONTENTION: There remains uncertainty surrounding specific public health interventions and novel therapies (including vaccines). How best to reduce transmission in the community during major outbreaks remains unclear. FUTURE DIRECTIONS: The potential of vaccine and therapeutic candidates in the event of another outbreak on this scale. . SEARCH STRATEGY: We searched all entries on the MedLine database/PubMed from 1976-2015 with the MeSH terms 'ebola', 'EVD', 'haemorrhagic fever'. We also reviewed publically available information via institutional websites from Governmental, NGOs and news organizations pertaining to the above search terms. PMID- 26872859 TI - Vertebral osteomyelitis in adults: an update. AB - INTRODUCTION: The incidence of vertebral osteomyelitis is increasing, attributed to an ageing population with inherent co-morbidities and improved case ascertainment. SOURCES OF DATA: References were retrieved from the PubMed database using the terms 'vertebral osteomyelitis' and 'spondylodiscitis' between January 1, 2009 and April 30, 2014 published in English as checked in May 2014 (>1000 abstracts checked). AREAS OF AGREEMENT: Blood cultures and whole spine imaging with magnetic resonance imaging are essential investigations. Thorough debridement is the mainstay of surgical management, although placing metalwork in active infection is becoming increasingly common. AREAS OF CONTROVERSY: The extent of pursuing spinal biopsies to determine aetiology, antimicrobial choices and duration, monitoring the response to treatment, and surgical techniques and timing all vary widely in clinical practice with heterogeneous studies limiting comparisons. Surgery, rather than conservative approaches, is being proposed as the default management choice, because it can, in carefully selected patients, offer faster reduction in pain scores and improved quality of life. AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies are needed to define the most effective technique for spinal biopsies to maximize determining aetiology. High-quality trials are required to provide an evidence base for both the medical and surgical management of vertebral osteomyelitis, including challenging medical management as the default option. PMID- 26872857 TI - The aetiopathogenesis of fatigue: unpredictable, complex and persistent. AB - BACKGROUND: Chronic fatigue syndrome is a common condition characterized by severe fatigue with post-exertional malaise, impaired cognitive ability, poor sleep quality, muscle pain, multi-joint pain, tender lymph nodes, sore throat or headache. Its defining symptom, fatigue is common to several diseases. AREAS OF AGREEMENT: Research has established a broad picture of impairment across autonomic, endocrine and inflammatory systems though progress seems to have reached an impasse. AREAS OF CONTROVERSY: The absence of a clear consensus view of the pathophysiology of fatigue suggests the need to switch from a focus on abnormalities in one system to an experimental and clinical approach which integrates findings across multiple systems and their constituent parts and to consider multiple environmental factors. GROWING POINTS: We discuss this with reference to three key factors, non-determinism, non-reductionism and self organization and suggest that an approach based on these principles may afford a coherent explanatory framework for much of the observed phenomena in fatigue and offers promising avenues for future research. AREAS TIMELY FOR DEVELOPING RESEARCH: By adopting this approach, the field can examine issues regarding aetiopathogenesis and treatment, with relevance for future research and clinical practice. PMID- 26872860 TI - S100A7: A rAMPing up AMP molecule in psoriasis. AB - S100A7 (psoriasin), an EF-hand type calcium binding protein localized in epithelial cells, regulates cell proliferation and differentiation. An S100A7 overexpression may occur in response to inflammatory stimuli, such in psoriasis, a chronic inflammatory autoimmune-mediated skin disease. Increasing evidence suggests that S100A7 plays critical roles in amplifying the inflammatory process in psoriatic skin, perpetuating the disease phenotype. This review will discuss the interactions between S100A7 and cytokines in psoriatic skin. Furthermore, we will focus our discussion on regulation and functions of S100A7 in psoriasis. Finally, we will discuss the possible use of S100A7 as therapeutic target in psoriasis. PMID- 26872861 TI - A rare finding of brown fat in bone marrow as a mimic for metastatic disease. PMID- 26872862 TI - Meeting report: 4th ISIRV antiviral group conference: Novel antiviral therapies for influenza and other respiratory viruses. AB - The International Society for Influenza and other Respiratory Virus Diseases (isirv) held its 4th Antiviral Group Conference at the University of Texas on 2-4 June, 2015. With emerging resistance to the drugs currently licensed for treatment and prophylaxis of influenza viruses, primarily the neuraminidase inhibitor oseltamivir phosphate (Tamiflu) and the M2 inhibitors amantadine and rimantadine, and the lack of effective interventions against other respiratory viruses, the 3-day programme focused on the discovery and development of inhibitors of several virus targets and key host cell factors involved in virus replication or mediating the inflammatory response. Virus targets included the influenza haemagglutinin, neuraminidase and M2 proteins, and both the respiratory syncytial virus and influenza polymerases and nucleoproteins. Therapies for rhinoviruses and MERS and SARS coronaviruses were also discussed. With the emerging development of monoclonal antibodies as therapeutics, the potential implications of antibody-dependent enhancement of disease were also addressed. Topics covered all aspects from structural and molecular biology to preclinical and clinical studies. The importance of suitable clinical trial endpoints and regulatory issues were also discussed from the perspectives of both industry and government. This meeting summary provides an overview, not only for the conference participants, but also for those interested in the current status of antivirals for respiratory viruses. PMID- 26872863 TI - Contrasting effect of new HCMV pUL54 mutations on antiviral drug susceptibility: Benefits and limits of 3D analysis. AB - Human cytomegalovirus (HCMV) resistance to antiviral drugs is a major drawback of repeated or long-duration treatment in immunocompromised patients. Resistance testing is usually performed by genotypic assays. For accurate interpretation of these assays, the role of new mutations in HCMV resistance has to be assessed. Two previously unknown UL54 single point mutations (D515Y and V787A) were characterized for phenotypic drug-resistance by marker transfer analysis using bacterial artificial chromosome (BAC) mutagenesis. Increases in 50% inhibitory concentrations of ganciclovir and foscarnet were found for both mutated recombinant strains showing that mutations D515Y and V787A induce resistance to both antivirals. Importantly, none of those impacted the viral growth kinetics. For a better understanding of their molecular resistance mechanisms, a 3D homology model was used to localize the mutated amino-acids in functional domains of UL54 and predict their impact on UL54 function and resistance. However, 3D homology model analysis has limits and phenotypic characterization using BAC-HCMV is still essential to measure the role of unknown mutations. PMID- 26872865 TI - Antioxidant and hyaluronidase inhibitory activities of diverse phenolics in Phyllanthus emblica. AB - Fifty-eight phenolic compounds isolated from Phyllanthus emblica were screened and compared for their in vitro and in vivo antioxidant properties, as well as hyaluronidase (HAase) inhibitory activities. Among them, 20 compounds showed to be promising antioxidants due to the stronger scavenging activity in both DPPH radical and Danio rerio reactive oxygen species assays, while nine compounds were potential HAase inhibitors with 100-fold stronger activities than that of the positive control, DSCG. The structure activity relationship was discussed. PMID- 26872864 TI - Lactimidomycin is a broad-spectrum inhibitor of dengue and other RNA viruses. AB - Dengue virus, a member of the Flaviviridae family, is a mosquito-borne pathogen and the causative agent of dengue fever. Despite the nearly 400 million new infections estimated annually, no vaccines or specific antiviral therapeutics are currently available. We identified lactimidomycin (LTM), a recently established inhibitor of translation elongation, as a potent inhibitor of dengue virus 2 infection in cell culture. The antiviral activity is observed at concentrations that do not affect cell viability. We show that Kunjin virus and Modoc virus, two other members of the Flavivirus genus, as well as vesicular stomatitis virus and poliovirus 1, are also sensitive to LTM. Our findings suggest that inhibition of translation elongation, an obligate step in the viral replication cycle, may provide a general antiviral strategy against fast-replicating RNA viruses. PMID- 26872867 TI - Education in Professionalism: Metrics or Culture? PMID- 26872866 TI - Rational biosynthetic approaches for the production of new-to-nature compounds in fungi. AB - Filamentous fungi have the ability to produce a wide range of secondary metabolites some of which are potent toxins whereas others are exploited as food additives or drugs. Fungal natural products still play an important role in the discovery of new chemical entities for potential use as pharmaceuticals. However, in most cases they cannot be directly used as drugs due to toxic side effects or suboptimal pharmacokinetics. To improve drug-like properties, including bioactivity and stability or to produce better precursors for semi-synthetic routes, one needs to generate non-natural derivatives from known fungal secondary metabolites. In this minireview, we describe past and recent biosynthetic approaches for the diversification of fungal natural products, covering examples from precursor-directed biosynthesis, mutasynthesis, metabolic engineering and biocombinatorial synthesis. To illustrate the current state-of-the-art, challenges and pitfalls, we lay particular emphasis on the class of fungal cyclodepsipeptides which have been studied longtime for product diversification and which are of pharmaceutical relevance as drugs. PMID- 26872868 TI - Coronary Computed Tomographic Angiography at Low Concentration of Contrast Agent and Low Tube Voltage in Patients with Obesity:: A Feasibility Study. AB - RATIONALE AND OBJECTIVES: Using lower tube voltage can reduce the exposure to radiation and the dose of contrast agent. However, lower tube voltage is often linked to more noise and poor image quality, which create a need for more effective technology to resolve this problem. To explore the feasibility of coronary computed tomographic angiography (CCTA) in patients with obesity at low tube voltage (100 kV) and low contrast agent concentration (270 mg/mL) using iterative reconstruction. MATERIALS AND METHODS: A total of 48 patients with body mass index greater than 30 kg/m(2) were included and randomly divided into two groups. Group A received a traditional protocol (iopromide 370 mg/mL + 120 kV); group B received a protocol with low tube voltage (100 kV), low contrast agent concentration (270 mg/mL), and iterative reconstruction. The effective dose (ED), average attenuation values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), the figure of merit (FOM), image quality scores, and the total iodine intake were compared. RESULTS: No significant differences in average CT attenuations, SNR, CNR, and subjective scores were noticed between the two groups (P > 0.05), whereas the FOM of group B was significantly higher than that of group A. Effective radiation dose, total iodine, and iodine injection rate in group B were lower than those of group A (P <0.01). CONCLUSIONS: In patients with obesity, isotonic contrast agent with low iodine concentration and low-dose CCTA were feasible. Substantial reduction in radiation dose and the iodine intake could be achieved without compromising the image quality. PMID- 26872869 TI - Age and total and free prostate-specific antigen levels for predicting prostate volume in patients with benign prostatic hyperplasia. AB - OBJECTIVES: To investigate the predictive values of free prostate-specific antigen (fPSA), total PSA (tPSA) and age on the prostate volume. METHODS: The data of 2148 patients with lower urinary tract symptoms were analyzed retrospectively. The patients who had transrectal ultrasonography guided 10 core biopsies owing to the findings obtained on digital rectal examination and presence of high PSA levels (PSA = 2.5-10 ng/dl), and proven to have BPH histopathologically were included in the study. Age, tPSA, fPSA and the prostate volumes (PV) of the patients were noted. RESULTS: One thousand patients that fulfilled the inclusion criteria were included in the study. The PV of the patients were significantly correlated with age, tPSA and fPSA (p < 0.001 and r = 0.307, p < 0.001 and r = 0.382, p < 0.001 and r = 0.296, respectively). On linear regression model, fPSA was found as a stronger predictive for PV (AUC = 0.75, p < 0.001) when compared to age (AUC = 0.64, p < 0.001), and tPSA (AUC = 0.69, p = 0.013). CONCLUSIONS: Although tPSA is an important prognostic factor for predicting PV, the predictive value of fPSA is higher. PV can easily be predicted by using age, and serum tPSA and fPSA levels. PMID- 26872870 TI - Home Visiting Programs: What the Primary Care Clinician Should Know. AB - Responsibilities for primary care clinicians are rapidly expanding ascomplexities in families' lives create increased disparities in health and developmental outcomes for young children. Despite the demands on primary care clinicians to promote health in the context of complex family and community factors, most primary care clinicians are operating in an environment of limited training and a shortage of resources for supporting families. Partnerships with evidence-based home visiting programs for very young children and their families can provide a resource that will help to reduce the impact of adverse early childhood experiences and facilitate health equity. Home visiting programs in the United States are typically voluntary and designed to be preventative in nature, although families are usually offered services based on significant risk criteria since the costs associated with universal approaches have been considered prohibitive. Programs may be funded within the health (physical orbehavioral/mental health), child welfare, early education, or early intervention systems or by private foundation dollars focused primarily on oneof the above systems (e.g., health), with a wide range of outcomes targeted by the programs and funders. Services may be primarily focused on the child, the parent, or parent-child interactions. Services include the development of targeted and individualized intervention strategies, better coaching of parents, and improved modeling of interactions that may assist struggling families. This paper provides a broad overview ofthe history of home visiting, theoretical bases of home visiting programs, key components of evidence-based models, outcomes typically targeted, research on effectiveness, cost information, challenges and benefits of home visiting, and funding/sustainability concerns. Significance for primary care clinicians isdescribed specifically and information relevant for clinicians is emphasized throughout the paper. PMID- 26872871 TI - Steroid-resistant protein-losing gastroenteropathy complicated with Sjogren's syndrome successfully treated with mizoribine. AB - A 64-year-old woman with leg edema was diagnosed with protein-losing gastroenteropathy and Sjogren's syndrome. Central venous nutrition led to infection of her catheter, ascites, and deep vein thrombosis. Following successful treatment of these conditions with antibiotics and anticoagulants, she was treated unsuccessfully with prednisolone and steroid pulse therapy. Mizoribine add-on markedly reduced edema and normalized serum albumin. This is the first report of a steroid-resistant protein-losing gastroenteropathy patient with Sjogren's syndrome successfully treated with mizoribine. PMID- 26872872 TI - Calcium homeostasis and low-frequency magnetic and electric field exposure: A systematic review and meta-analysis of in vitro studies. AB - Low frequency magnetic field (LF MF) exposure is recurrently suggested to have the ability to induce health effects in society. Therefore, in vitro model systems are used to investigate biological effects of exposure. LF MF induced changes of the cellular calcium homeostasis are frequently hypothesised to be the possible target, but this hypothesis is both substantiated and rejected by numerous studies in literature. Despite the large amount of data, no systematic analysis of in vitro studies has been conducted to address the strength of evidence for an association between LF MF exposure and calcium homeostasis. Our systematic review, with inclusion of 42 studies, showed evidence for an association of LF MF with internal calcium concentrations and calcium oscillation patterns. The oscillation frequency increased, while the amplitude and the percentage of oscillating cells remained constant. The intracellular calcium concentration increased (SMD 0.351, 95% CI 0.126, 0.576). Subgroup analysis revealed heterogeneous effects associated with the exposure frequency, magnetic flux density and duration. Moreover, we found support for the presence of MF sensitive cell types. Nevertheless, some of the included studies may introduce a great risk of bias as a result of uncontrolled or not reported exposure conditions, temperature ranges and ambient fields. In addition, mathematical calculations of the parasitic induced electric fields (IEFs) disclosed their association with increased intracellular calcium. Our results demonstrate that LF MF might influence the calcium homeostasis in cells in vitro, but the risk of bias and high heterogeneity (I(2)>75%) weakens the analyses. Therefore any potential clinical implications await further investigation. PMID- 26872873 TI - Degenerative disease of the lumbar spine. AB - In the last 25 years, scientific research has brought about drastic changes in the concept of low back pain and its management. Most imaging findings, including degenerative changes, reflect anatomic peculiarities or the normal aging process and turn out to be clinically irrelevant; imaging tests have proven useful only when systemic disease is suspected or when surgery is indicated for persistent spinal cord or nerve root compression. The radiologic report should indicate the key points of nerve compression, bypassing inconsequential findings. Many treatments have proven inefficacious, and some have proven counterproductive, but they continue to be prescribed because patients want them and there are financial incentives for doing them. Following the guidelines that have proven effective for clinical management improves clinical outcomes, reduces iatrogenic complications, and decreases unjustified and wasteful healthcare expenditures. PMID- 26872874 TI - Temporal-specific roles of Rac1 during vascular development and retinal angiogenesis. AB - Angiogenesis, the formation of new blood vessels by remodeling and growth of pre existing vessels, is a highly orchestrated process that requires a tight balance between pro-angiogenic and anti-angiogenic factors and the integration of their corresponding signaling networks. The family of Rho GTPases, including RhoA, Rac1, and Cdc42, play a central role in many cell biological processes that involve cytoskeletal changes and cell movement. Specifically for Rac1, we have shown that excision of Rac1 using a Tie2-Cre animal line results in embryonic lethality in midgestation (embryonic day (E) 9.5), with multiple vascular defects. However, Tie2-Cre can be also expressed during vasculogenesis, prior to angiogenesis, and is active in some hematopoietic precursors that can affect vessel formation. To circumvent these limitations, we have now conditionally deleted Rac1 in a temporally controlled and endothelial-restricted fashion using Cdh5(PAC)-iCreERT2 transgenic mice. In this highly controlled experimental in vivo system, we now show that Rac1 is required for embryonic vascular integrity and angiogenesis, and for the formation of superficial and deep vascular networks in the post-natal developing retina, the latter involving a novel specific function for Rac1 in vertical blood vessel sprouting. Aligned with these findings, we show that RAC1 is spatially involved in endothelial cell migration, invasion, and radial sprouting activities in 3D collagen matrix in vitro models. Hence, Rac1 and its downstream molecules may represent potential anti-angiogeneic therapeutic targets for the treatment of many human diseases that involve aberrant neovascularization and blood vessel overgrowth. PMID- 26872875 TI - Contribution of hedgehog signaling to the establishment of left-right asymmetry in the sea urchin. AB - Most bilaterians exhibit a left-right asymmetric distribution of their internal organs. The sea urchin larva is notable in this regard since most adult structures are generated from left sided embryonic structures. The gene regulatory network governing this larval asymmetry is still a work in progress but involves several conserved signaling pathways including Nodal, and BMP. Here we provide a comprehensive analysis of Hedgehog signaling and it's contribution to left-right asymmetry. We report that Hh signaling plays a conserved role to regulate late asymmetric expression of Nodal and that this regulation occurs after Nodal breaks left-right symmetry in the mesoderm. Thus, while Hh functions to maintain late Nodal expression, the molecular asymmetry of the future coelomic pouches is locked in. Furthermore we report that cilia play a role only insofar as to transduce Hh signaling and do not have an independent effect on the asymmetry of the mesoderm. From this, we are able to construct a more complete regulatory network governing the establishment of left-right asymmetry in the sea urchin. PMID- 26872876 TI - Mouse sperm begin to undergo acrosomal exocytosis in the upper isthmus of the oviduct. AB - Recent evidence demonstrated that most fertilizing mouse sperm undergo acrosomal exocytosis (AE) before binding to the zona pellucida of the eggs. However, the sites where fertilizing sperm could initiate AE and what stimuli trigger it remain unknown. Therefore, the aim of this study was to determine physiological sites of AE by using double transgenic mouse sperm, which carried EGFP in the acrosome and DsRed2 fluorescence in mitochondria. Using live imaging of sperm during in vitro fertilization of cumulus-oocyte complexes, it was observed that most sperm did not undergo AE. Thus, the occurrence of AE within the female reproductive tract was evaluated in the physiological context where this process occurs. Most sperm in the lower segments of the oviduct were acrosome-intact; however, a significant number of sperm that reached the upper isthmus had undergone AE. In the ampulla, only 5% of the sperm were acrosome-intact. These results support our previous observations that most of mouse sperm do not initiate AE close to or on the ZP, and further demonstrate that a significant proportion of sperm initiate AE in the upper segments of the oviductal isthmus. PMID- 26872877 TI - Delivery of ibuprofen by natural macroporous sporopollenin exine capsules extracted from Phoenix dactylifera L. AB - Sporopollenin macroporous capsules (SMCs) were extracted from date palm (Phoenix dactylifera L.) spores and coated by a natural polymer composite (chitosan with glutaraldehyde). The polymer coated macroporous capsules SMC@poly were used in the in vitro-controlled delivery of ibuprofen. The materials obtained were characterized through spectral, thermal, scanning electron microscopy (SEM), X ray diffraction (XRD), and nitrogen adsorption-desorption isotherms. The IBU loading and releasing was studied by investigating the changes in various factors such as pH, temperature, and initial concentration. The results revealed that the loading of IBU increased when the concentration of IBU was decreased, following the Langmuir adsorption isotherm. The maximum loading of the IBU was observed at pH6.0 (97.2%, with 50mg/mL). The releasing results indicate that IBU was released faster when the pH was changed from 1.4 to 7.4. In addition, the cytotoxicity of the SMC, SMC@poly, and SMC@poly-IBU were tested against human intestinal Caco-2 cell line using MTT assay, and the results revea'led that all the materials in this study were biocompatible. PMID- 26872878 TI - Special issue: Extracellular matrix: Therapeutic tools and targets in cancer treatment. AB - Extracellular matrix (ECM) constituents play not only structural roles during development and tissue homeostasis, but also many biological functions throughout life. Molecular diversity and a vast interactome provide the basis for this multi functionality. Moreover, native or processed ECM molecules interact with various receptors, thereby activating signaling pathways that control cell differentiation, proliferation, adhesion and migration, all relevant to tumor biology. Thus, there is an emerging field focused on exploiting ECM components as novel therapeutic targets in the treatment of cancer and other diseases, providing potent tools to advance drug delivery and tissue penetration. In this special issue we provide a critical appraisal of this emerging field focusing on: 1) ECM proteins (matricellular proteins, collagen, elastin, fibronectin, proteoglycans), integrins, and protease-facilitated drug delivery; 2) ECM-derived therapeutics (hyaluronan, heparin, heparan sulfate), 3) ECM-like biomaterials, and 4) ECM as critical determinant in drug efficacy, with special emphasis on applications in tumor treatment. PMID- 26872879 TI - Environmental cues and attempts to change in daily cannabis users: An intensive longitudinal study. AB - INTRODUCTION: We tested whether environmental cues prompt or inhibit quit or reduction attempts among heavy cannabis users. METHODS: We recruited 196 daily cannabis users who intended to stop or reduce at some point in the next 3 months. Users called an Interactive Voice Response system daily over 3 months to report on cues that might prompt an attempt to quit or reduce (e.g., a request to stop), cues that might inhibit a quit/reduction attempt (e.g., someone offering cannabis), cannabis use, and attempts to stop or reduce cannabis. No treatment was provided. RESULTS: Our major findings were (a) cost and health/psychological problems were the most common prompting cues, and seeing others use and being offered cannabis were the most common inhibiting cues, (b) the number of different types of prompting cues prospectively predicted an increase in attempts to change in a dose-related manner, (c) more proximal cues appeared to be more strongly related to change, (d) requests to stop or reduce, and physical or psychological problems from cannabis, best predicted change attempts, and (e) inhibiting cues did not consistently predict the probability of an attempt to change. CONCLUSION: These preliminary results suggest several environmental cues prompt attempts to change cannabis use. Thus, interventions to increase the frequency of these cues, and specifically requests to stop or reduce cannabis use, and reinforcing concerns about health and mental adverse events from cannabis use, may increase cannabis reduction or cessation. PMID- 26872881 TI - Partial papillary muscle rupture following percutaneous mitral valvuloplasty without mitral regurgitation. PMID- 26872880 TI - The impact of an alcohol harm reduction intervention on interpersonal violence and engagement in sex work among female sex workers in Mombasa, Kenya: Results from a randomized controlled trial. AB - AIMS: To evaluate whether an alcohol harm reduction intervention was associated with reduced interpersonal violence or engagement in sex work among female sex workers (FSWs) in Mombasa, Kenya. DESIGN: Randomized controlled trial. SETTING: HIV prevention drop-in centers in Mombasa, Kenya. PARTICIPANTS: 818 women 18 or older in Mombasa who visited HIV prevention drop-in centers, were moderate-risk drinkers and engaged in transactional sex in past six months (410 and 408 in intervention and control arms, respectively). INTERVENTION: 6 session alcohol harm reduction intervention. COMPARATOR: 6 session non-alcohol related nutrition intervention. MEASUREMENTS: In-person interviews were conducted at enrollment, immediately post-intervention and 6-months post-intervention. General linear mixed models examined associations between intervention assignment and recent violence (physical violence, verbal abuse, and being robbed in the past 30 days) from paying and non-paying sex partners and engagement in sex work in the past 30 days. FINDINGS: The alcohol intervention was associated with statistically significant decreases in physical violence from paying partners at 6 months post intervention and verbal abuse from paying partners immediately post-intervention and 6-months post-intervention. Those assigned to the alcohol intervention had significantly reduced odds of engaging in sex work immediately post-intervention and 6-months post-intervention. CONCLUSIONS: The alcohol intervention was associated with reductions in some forms of violence and with reductions in engagement in sex work among FSWs in Mombasa, Kenya. PMID- 26872882 TI - The long-term survival of Acinetobacter baumannii ATCC 19606(T) under nutrient deprived conditions does not require the entry into the viable but non-culturable state. AB - Acinetobacter baumannii possesses a tremendous potential to thrive under hostile conditions. To learn more about its survival strategy and capacity to persist in the environment, we studied the effect of temperature, nutrient deprivation and dryness on the long-term survival of two A. baumannii strains (ATCC 19606(T) and a clinical isolate). Our results revealed that both strains show a great persistence under stress that appears to involve a bust-and-boom strategy. Bacterial survival was differentially affected by temperature and physical environment: Desiccation favored cell resistance to stress at 20 and 37 degrees C, while survival in aqueous environments was temperature dependent and led to changes in several cellular characteristics. In addition, we tested the ability of the A. baumannii ATCC 19606(T) strain to form biofilms by monitoring the expression of adhesion-/biofilm-related genes (ompA, bfmR and csuAB). The observed downregulation of these genes suggests that the potential difficulties to adhere to solid surfaces and form biofilms likely limit the capacity of starved cells to spread and colonize abiotic surfaces. PMID- 26872883 TI - Automatic tracking of laparoscopic instruments for autonomous control of a cameraman robot. AB - BACKGROUND: An automated instrument tracking procedure was designed and developed for autonomous control of a cameraman robot during laparoscopic surgery. MATERIAL AND METHODS: The procedure was based on an innovative marker-free segmentation algorithm for detecting the tip of the surgical instruments in laparoscopic images. A compound measure of Saturation and Value components of HSV color space was incorporated that was enhanced further using the Hue component and some essential characteristics of the instrument segment, e.g., crossing the image boundaries. The procedure was then integrated into the controlling system of the RoboLens cameraman robot, within a triple-thread parallel processing scheme, such that the tip is always kept at the center of the image. RESULTS: Assessment of the performance of the system on prerecorded real surgery movies revealed an accuracy rate of 97% for high quality images and about 80% for those suffering from poor lighting and/or blood, water and smoke noises. A reasonably satisfying performance was also observed when employing the system for autonomous control of the robot in a laparoscopic surgery phantom, with a mean time delay of 200ms. CONCLUSION: It was concluded that with further developments, the proposed procedure can provide a practical solution for autonomous control of cameraman robots during laparoscopic surgery operations. PMID- 26872884 TI - Model-based meta-analysis for development of a population-pharmacokinetic (PPK) model for Vitamin D3 and its 25OHD3 metabolite using both individual and arm level data. AB - Clinical studies investigating relationships between D3 and 25OHD3 vary in dosing regimen, assays, demographics, and control of exogenous D3. This leads to uncertain and conflicting exposure-related associations with D3 and 25OHD3. To elucidate this parent-metabolite system, a PPK model was developed to predict mean D3 and 25OHD3 exposure from varied doses and administration routes. Sources of exposure variability related to metabolite baseline, weight, and assay type were explored. Specific search criteria were used in PUBMED to identify public source PK data pertaining to D3 and 25OHD3 in healthy or osteoporotic populations. Overall 57 studies representing 5395 individuals were selected, including 25 individual-level profiles and treatment-arm data. IV, oral, single and multiple dose data were used, with D3 and 25OHD3 dosing. A nonlinear mixed effects model was developed to simultaneously model PK dispositions of D3 and 25OHD3 (NONMEM v7.2), which were described by 2-compartment models with nonlinear and linear clearances, respectively. Proportional and additive assay variances were included on the 25OHD3 prediction. Unit-level random effects were weighted by treatment-arm size. D3 model estimates, relative to bioavailability were: maximum rate of metabolism ([Formula: see text], 1.62 nmol/h), Michaelis-Menten constant ([Formula: see text], 6.39 nmol/L), central volume of distribution ([Formula: see text], 15.5 L), intercompartmental clearance ([Formula: see text], 0.185 L/h), peripheral volume of distribution ([Formula: see text], 2333 L/h), and baseline concentration ([Formula: see text], 3.75 nmol/L). For 25OHD3 ([Formula: see text] = metabolite): [Formula: see text] = 0.0153 L/h, [Formula: see text] = 4.35 L, [Formula: see text] = 6.87 L, [Formula: see text] = 0.0507 L/h. Simulations of 25OHD3 concentration indicated an inverse relationship between 25OHD3 baseline and response, as well as a less than proportional 25OHD3 response. Estimation of assay bias parameters suggested that HPLC-MS and RIA produced similar measurement results, whereas CPBA and CHEMI are over-predictive of 25OHD3 concentration, relative to HPLC-MS. PMID- 26872885 TI - Assessing Potential Conservation and Restoration Areas of Freshwater Fish Fauna in the Indian River Basins. AB - Conservation efforts globally are skewed toward terrestrial ecosystems. To date, conservation of aquatic ecosystems, in particular fish fauna, is largely neglected. We provide a country-wide assessment of Indian river ecosystems in order to identify and prioritize areas for protection and restoration of freshwater fish fauna. Using various biodiversity and anthropogenic attributes, coupled with tools of ecological modeling, we delineated areas for fish fauna conservation and restoration in the 20 major river basins of India. To do this, we used prioritization analyses and reserve selection algorithms to derive conservation value index (CVI) and vulnerability index (VI) of the river basins. CVI was estimated using endemicity, rarity, conservation value, and taxonomic singularity, while VI was estimated using a disturbance index derived from percent geographic area of the basin under human settlements, human population density, predominant land use, and total number of exotic fish species in each basin. The two indices, CVI and VI, were converted into geo-referenced maps, and each map was super-imposed onto species richness and forest cover maps, respectively. After superimposition, areas with high CVI and low VI shade intensities were delineated for conservation, while areas with high CVI and high VI shade intensities were demarcated for restoration. In view of the importance of freshwater fish for human livelihoods and consumption, and ecosystems of India's rivers, we call for urgent attention to the conservation of their fish fauna along with restoration of their degraded habitats. PMID- 26872886 TI - Spatial Variations of Soil Microbial Activities in Saline Groundwater-Irrigated Soil Ecosystem. AB - Spatial variations of soil microbial activities and its relationship with environmental factors are very important for estimating regional soil ecosystem function. Based on field samplings in a typical saline groundwater-irrigated region, spatial variations of soil microbial metabolic activities were investigated. Combined with groundwater quality analysis, the relationship between microbial activities and water salinity was also studied. The results demonstrated that moderate spatial heterogeneity of soil microbial activities presented under the total dissolved solids (TDS) of groundwater ranging from 0.23 to 12.24 g L(-1). Groundwater salinity and microbial activities had almost opposite distribution characteristics: slight saline water was mainly distributed in west Baqu and south Quanshan, while severe saline and briny water were dominant in east Baqu and west Huqu; however, total AWCD was higher in the east center and southwest of Baqu and east Huqu, while it was lower in east Baqu and northwest Huqu. The results of correlation analyses demonstrated that high salinity groundwater irrigation had significantly adverse effects on soil microbial activities. Major ions Ca(2+), Mg(2+), Cl(-), and SO4(2-) in groundwater decisively influenced the results. Three carbon sources, carbohydrates, amines, and phenols, which had minor utilization rates in all irrigation districts, were extremely significantly affected by high-salinity groundwater irrigation. The results presented here offer an approach for diagnosing regional soil ecosystem function changes under saline water irrigation. PMID- 26872887 TI - Reversing the Effect of Oral Anticoagulant Drugs: Established and Newer Options. AB - The vitamin K antagonists (VKAs) have been the standard (and only) oral anticoagulants used for the long-term treatment or prevention of venous thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy induced by VKAs can be reversed with vitamin K, and in urgent situations, the vitamin K-dependent coagulation factors can be replaced by transfusion. In the last decade, a new class of oral anticoagulants has been developed, direct oral anticoagulants that bind to a specific coagulation factor and neutralize it. These compounds were shown to be effective and safe compared with the VKAs and were licensed for specific indications, but without a specific reversal agent. The absence of a reversal agent is a barrier to more widespread use of these agents. Currently, for the management of major life-threatening bleeding with the direct oral anticoagulants, most authorities recommend the use of four factor prothrombin complex concentrates. There are now three reversal agents in development and poised to enter the market. Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin. PMID- 26872888 TI - Associations between self-reported concussion with later violence injury among Australian early adolescents. AB - Background: There is growing research finding associations between adolescents' concussion and negative outcomes, including violence, rarely however are the experiences of community-based early adolescents considered. Methods: This study examined associations between reports of concussion (Time-1) and reports of violence 1-year later (Time-2). Australian adolescents from 13 high-schools completed two identical surveys administered 12-months apart (n = 734 retained, initial mean age = 13.45). Results: At the first survey, 91 students (13%) reported they had a concussion, and of these students, 40% reported seeing a doctor/attending hospital during the prior 3 months. Both self-reported experience of violent injury (from getting in a fight) and violent behaviour (getting in a fight) were predicted by reports of concussion in Year 9. This prediction held, when adding sex, Year 9 reports of violence, alcohol use, truancy and engagement in passenger and driving risk-taking to logistic regression models. Year 9 concussion was not predictive of later injury in other contexts, including transportation, falls or sports. Conclusion: The study highlights the need to understand concussion among community-based early adolescents including consider associations with violence. PMID- 26872889 TI - Safety and efficacy of dual direct-acting antiviral therapy (daclatasvir and asunaprevir) for chronic hepatitis C virus genotype 1 infection in patients on hemodialysis. AB - BACKGROUND: Hepatitis C virus (HCV) infection is a major comorbidity in patients receiving hemodialysis. Interferon-based antiviral therapy to eradicate HCV is less effective in patients receiving hemodialysis than patients without renal dysfunction. Recently reported combination therapy with two oral direct-acting antiviral drugs, daclatasvir and asunaprevir, both of which are metabolized in the liver and excreted into the bile ducts, reportedly showed a high rate of HCV eradication. We evaluated the safety and efficacy of this therapy in patients receiving hemodialysis. METHODS: The safety and viral responses were compared among patients infected with HCV genotype 1, between 28 patients receiving hemodialysis, and propensity score-matched 56 patients without renal dysfunction. RESULTS: The reduction in serum HCV RNA levels 1 day after the start of therapy was significantly larger (p = 0.0329) and the disappearance of serum HCV RNA occurred significantly earlier (p = 0.0017) in patients receiving hemodialysis than those without renal dysfunction. The rates of sustained virologic response, i.e., the eradication of HCV, were comparable between two groups; the rate of SVR12 was 100 % in patients receiving hemodialysis and 94.6 % in patients without renal dysfunction. No adverse constitutional events were observed in either of the groups. The elevation of serum alanine aminotransferase levels, a known adverse effect of these drugs, was observed in comparable rate of patients between the two groups. CONCLUSIONS: The therapy with daclatasvir and asunaprevir has high antiviral efficacy in patients receiving hemodialysis with a comparable safety profile to patients without renal dysfunction. PMID- 26872891 TI - Increased expressions of claudin 4 and 7 in atypical adenomatous hyperplasia and adenocarcinoma of the lung. AB - Abnormal expression of claudin (Cldn), the main constituent of tight junctions, may play a crucial role in carcinogenesis. To elucidate these abnormalities of tight junctions in lung adenocarcinoma during carcinogenesis, we examined immunohistochemical expressions of Cldn4 and Cldn7 in human lung resection materials. Lung resection specimens from 86 patients were studied, including 16 atypical adenomatous hyperplasia (AAH), 19 adenocarcinoma in situ (AIS), 32 invasive adenocarcinoma (ADC), 5 AIS with AAH, 2 ADC with AAH, 10 ADC with AIS, and 2 ADC with AIS and AAH. The immunohistochemical staining (IHC) score was defined for both the extent and intensity of staining. IHC score for Cldn4 in AIS and ADC was significantly higher than that in alveolar epithelium (AE) and AAH (p < 0.001 for both). In addition, the AAH score was significantly higher than that in AE (p < 0.001). The Cldn7 score in ADC was significantly increased compared with AE and AAH (p < 0.001 for both). These results suggested that increase of Cldn4-expression may be involved in early molecular events during carcinogenesis of adenocarcinoma, whereas increase of Cldn7-expression may be associated with tumor invasion or progression. PMID- 26872890 TI - Intestine-specific homeobox (ISX) induces intestinal metaplasia and cell proliferation to contribute to gastric carcinogenesis. AB - BACKGROUND: Helicobacter pylori induces chronic inflammation and intestinal metaplasia (IM) through genetic and epigenetic changes and activation of intracellular signaling pathways that contribute to gastric carcinogenesis. However, the precise mechanism of IM in gastric carcinogenesis has not been fully elucidated. We previously found that intestine-specific homeobox (ISX) mRNA expression increased in organoids cultured from Helicobacter-infected mouse mucosa. In this study, we elucidate the role of ISX in the development of IM and gastric carcinogenesis. METHODS: ISX expression was assessed in Helicobacter infected mouse and human gastric mucosa. MKN45 gastric cancer cells were co cultured with H. pylori to determine whether Helicobacter infection induced ISX expression. We established stable MKN45 transfected cells expressing ISX (Stable ISX MKN45) and performed a spheroid colony formation assay and a xenograft model. We performed ISX immunohistochemistry in cancer and adjacent gastric tissues. RESULTS: ISX expression was increased in mouse and human gastric mucosa infected with Helicobacter. The presence of IM and H. pylori infection in human stomach was correlated with ISX expression. H. pylori induced ISX mRNA and protein expression. CDX1/2, cyclinD1, and MUC2 were upregulated in Stable-ISX MKN45, whereas MUC5AC was downregulated. Stable-ISX MKN45 cells formed more spheroid colonies, and had high tumorigenic ability. ISX expression in gastric cancer and adjacent mucosa were correlated. CONCLUSIONS: ISX expression induced by H. pylori infection may lead to IM and hyperproliferation of gastric mucosa through CDX1/2 and cyclinD1 expression, contributing to gastric carcinogenesis. PMID- 26872892 TI - The Effect of a High-Fat Meal on the Pharmacokinetics of Ixazomib, an Oral Proteasome Inhibitor, in Patients With Advanced Solid Tumors or Lymphoma. AB - Ixazomib is the first oral proteasome inhibitor to be investigated in the clinic. This clinical study assessed whether the pharmacokinetics of ixazomib would be altered if administered after a high-calorie, high-fat meal. In a 2-period, 2 sequence, crossover study design, adult patients with advanced solid tumors or lymphoma received a 4-mg oral dose of ixazomib as immediate-release capsules on day 1 without food (fasted, administered following an overnight fast) or with food (fed, following consumption of a high-calorie, high-fat meal), followed by another dose on day 15 in the alternate food intake condition (fasted to fed or fed to fasted). Twenty-four patients were enrolled; of these, 15 were included in the pharmacokinetic-evaluable population. Administration of ixazomib after a high fat meal reduced both the rate and extent of absorption of ixazomib. Under fed conditions, the median time to peak plasma concentration (Tmax ) of ixazomib was delayed by approximately 3 hours compared with administration in the fasted state (1.02 hours vs 4.0 hours), and there was a 28% reduction in total systemic exposure (area under the curve, AUC) and a 69% reduction in peak plasma concentration (Cmax ). Together, the results support the administration of ixazomib on an empty stomach, at least 1 hour before or at least 2 hours after food. These recommendations are reflected in the United States Prescribing Information for ixazomib (clinicaltrials.gov identifier NCT01454076). PMID- 26872893 TI - Change in Posterior Tibial Slope After Open-Wedge and Closed-Wedge High Tibial Osteotomy: A Meta-analysis. AB - BACKGROUND: It is unclear whether open- or closed-wedge high tibial osteotomy (HTO) results in significant changes in posterior tibial slope, with no consensus on the magnitude of such changes. Furthermore, methods of measuring posterior tibial slope differ among studies. This meta-analysis was therefore designed to evaluate whether posterior tibial slope increases after open-wedge HTO and decreases after closed-wedge HTO and to quantify the magnitudes of the slope changes after open- and closed-wedge HTO using various methods of measuring posterior tibial slope. HYPOTHESIS: Posterior tibial slope increases after open wedge and decreases after closed-wedge HTO. The magnitude of change is similar for the 2 methods, and the value obtained for posterior tibial slope change is affected by the method of measurement. STUDY DESIGN: Meta-analysis. METHODS: Multiple comprehensive databases, including MEDLINE, EMBASE, the Cochrane Library, and KoreaMed, were searched for studies that evaluated the posterior slope of the proximal tibia in patients who had undergone open- and/or closed wedge HTO. Studies were included that compared pre- and postoperative posterior tibial slopes, regardless of measurement method, including anterior and posterior tibial cortex or tibial shaft axis as a reference line, in patients who underwent open- or closed-wedge HTO. The quality of each included study was appraised with the Newcastle-Ottawa Scale. RESULTS: Twenty-seven studies were included in the meta-analysis. Pooled data, which included subgroups of 3 methods, showed that posterior tibial slope increased 2.02 degrees (95% CI, 2.66 degrees to 1.38 degrees ; P = .005) after open-wedge HTO and decreased 2.35 degrees (95% CI, 1.38 degrees to 3.32 degrees ; P < .001) after closed-wedge HTO. CONCLUSION: This meta-analysis confirmed that posterior tibial slope increased after open wedge HTO and decreased after closed-wedge HTO when the results of a variety of measurement methods were pooled. The magnitude of change after open- and closed wedge HTO was similar and small (approximately 2 degrees ), suggesting that both osteotomy techniques may have little effect on the biomechanics of the cruciate ligaments. PMID- 26872894 TI - The Functional and Structural Outcomes of Arthroscopic Iliopsoas Release. AB - BACKGROUND: Arthroscopic release of the iliopsoas tendon may alleviate pain associated with internal snapping hip, but previous reports of physical function, hip strength, and muscle atrophy after surgery are mixed. HYPOTHESIS: The hips of patients who underwent arthroscopic iliopsoas release would demonstrate significantly reduced hip flexion strength and iliopsoas muscle volume when compared with their contralateral hips and the hips of patients who underwent hip arthroscopy without psoas release. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Eighteen patients who underwent hip arthroscopy with iliopsoas release for symptomatic internal snapping hip and concomitant femoroacetabular impingement (FAI) and/or chondrolabral damage (release group) and 18 patients who underwent arthroscopy for FAI and/or chondrolabral damage without iliopsoas release (control group) were evaluated at a mean of 21 months (range, 16-30 months) postoperatively. Magnetic resonance images were performed and segmented to calculate iliopsoas volume. Isometric hip flexion strength was evaluated in the supine and seated positions with a custom testing apparatus. Differences between groups and differences between the operative and nonoperative limbs within groups were compared with unpaired and paired t tests, respectively. RESULTS: In the release group, the iliopsoas muscle of the surgical limb was significantly smaller (288 +/- 98 vs 384 +/- 113 cm(3), P < .001) and weaker in the seated position (13 +/- 4.7 vs 17 +/- 5.8 kg, P < .001) than the contralateral limb. Compared with the control group, the release group demonstrated a greater percentage decrease in iliopsoas volume on magnetic resonance imaging (-25% +/- 9.1% vs -0.6% +/- 4.6%, P < .001) and seated hip flexion strength (-19% +/- 16% vs -3.9% +/- 20%, P = .018) between the operative and contralateral limbs. There were no significant differences in supine strength between limbs or groups (all P > .168). CONCLUSION: Arthroscopic iliopsoas release results in iliopsoas atrophy with a 25% volume loss and a 19% reduction in seated hip flexion strength. PMID- 26872896 TI - A unique case of extra-group infant adoption in free-ranging Angola black and white colobus monkeys (Colobus angolensis palliatus). AB - Infant adoption has been reported in a variety of primate taxa both in captive and natural settings. Adoption by females may be adaptive by increasing inclusive fitness via shared genes between adoptive mother and adoptee or by providing valuable maternal practice which, in turn, may increase the female's future reproductive success. Others have argued that adoption may be non-adaptive and the result of a general attraction toward infants. Our study examines a unique case of adoption by an adult female Angola black and white colobus monkey (Colobus angolensis palliatus) who adopted an extra-group infant alongside her own biological infant. We compare infant behaviors and mother-infant interactions between biological infant and adoptee and then compare both biological infant and adoptee behavioral profiles to those of infants under normal circumstances. Data were collected from July 2014 to June 2015 on three habituated groups in the Diani Forest of Kenya. Scan sampling and pooled data were used to create daily and monthly behavioral profiles for the biological infant and adoptee, as well as a mean monthly profile of four infants under normal circumstances. Data include time spent (1) clinging to mother/adoptive mother, (2) clinging to another individual, (3) behaving independently, and (4) behaving in close proximity to mother/adoptive mother. Initially, the adoptee struggled to achieve behavioral profiles consistent with those of the biological infant and normal colobus infants of the same age as he spent significantly more time moving independently and significantly less time clinging to the adoptive mother. After the mysterious death of the biological infant in mid-January 2015, the adoptee assumed a behavioral profile similar to that of infants under normal conditions. This case does not support adaptive hypotheses for adoption (i.e., inclusive fitness or learning to mother). Instead, because the biological infant died, possibly due to the presence of the adoptee, we argue that this case of infant adoption was non adaptive. Ultimately, this adoption appears to have been an outcome of the adoptee's persistent desire to be cared for and the female's strong propensity to engage in allomaternal behavior. PMID- 26872897 TI - Rabbit model for osteoarthrosis of the temporomandibular joint as a basis for assessment of outcomes after intervention. AB - Osteoarthritis can be induced in the temporomandibular joint (TMJ) by primary or secondary trauma, or overloading of the joint. We have therefore systematically evaluated the histological progression of experimental osteoarthritis induced by a high concentration of monosodium iodoacetate into the rabbit TMJ. These findings may contribute to the establishment of a protocol to investigate the benefits of treatment of osteoarthritis of the TMJ. We used 21 male New Zealand rabbits; the 15 in the test group were given an intra-articular injection of monosodium iodoacetate 10mg/ml into the right TMJ and were killed after 60 (n=5), 80 (n=5), and 100 days (n=5). The six in the control group were given an injection of saline into the right TMJ. The assessment system for osteoarthritis based on six grades was used for the histological analysis of severity. The model was effective in producing histological changes in the cartilage consistent with those found in osteoarthritis at all time points. The within-group analysis indicated that the disease did not progress after 60 days. The successful induction of osteoarthritis in this way, its stabilisation after 60 days, and the appropriate size of the animal suggest that this experimental model is ideal for future studies of the effectiveness of treatment in osteoarthritis of the TMJ. PMID- 26872895 TI - Outcomes After Isolated Medial Patellofemoral Ligament Reconstruction for the Treatment of Recurrent Lateral Patellar Dislocations: A Systematic Review and Meta-analysis. AB - BACKGROUND: A patellar dislocation is a common knee injury in the young, athletic patient population. Recent trends indicate that the use of long-term nonoperative treatment is decreasing, and surgical intervention is more commonly recommended for those patients who fail initial nonoperative management with recurrent patellar dislocations. Medial patellofemoral ligament (MPFL) reconstruction has become increasingly utilized in this regard. PURPOSE: To evaluate outcomes, particularly return to sports and its relationship to postoperative instability, of isolated MPFL reconstruction for the treatment of recurrent patellar dislocations. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A review of the current literature was performed using the terms "medial patellofemoral ligament reconstruction" and "MPFL reconstruction" in the electronic search engines PubMed and EBSCOhost (CINAHL, MEDLINE, SPORTDiscus) on July 29, 2015, yielding 1113 abstracts for review. At the conclusion of the search, 14 articles met the inclusion criteria and were included in this review of the literature. Means were calculated for population size, age, follow-up time, and postoperative Tegner scores. Pooled estimates were calculated for postoperative Kujala scores, return to play, total risk of postoperative instability, risk of positive apprehension sign, and risk of reoperation. RESULTS: The mean patient age associated with MPFL reconstruction was 24.4 years, with a mean postoperative Tegner score of 5.7. The pooled estimated mean postoperative Kujala score was 85.8 (95% CI, 81.6-90.0), with 84.1% (95% CI, 71.1%-97.1%) of patients returning to sports after surgery. The pooled total risk of recurrent instability after surgery was 1.2% (95% CI, 0.3%-2.1%), with a positive apprehension sign risk of 3.6% (95% CI, 0%-7.2%) and a reoperation risk of 3.1% (95% CI, 1.1%-5.0%). CONCLUSION: A high percentage of young patients return to sports after isolated MPFL reconstruction for chronic patellar instability, with short-term results demonstrating a low incidence of recurrent instability, postoperative apprehension, and reoperations. PMID- 26872898 TI - Local heating of the wound with dressings soaked in saline at 42 degrees C can reduce postoperative bleeding: a single-blind, split-mouth, randomised controlled clinical trial. AB - Control of bleeding is essential during oral procedures. Although various chemical agents have been introduced and tested, hot water dressing has not to our knowledge been assessed before. Studies of operations for epistaxis or sinus conditions have suggested that irrigation with hot water can reduce bleeding, so we hypothesised that it might be effective in reducing bleeding after extraction too. Ten patients who required bilateral extractions took part in this split mouth, randomised, single-blind, controlled clinical trial. After extraction, sockets were packed with similar gauze dressings soaked in normal saline 4 ml at room temperature (control) and warmed to 42 degrees C (experimental). The extent of bleeding on each side was measured by subtracting the original weight of the gauze from its weight after absorption of blood. The difference between the weights was compared using Student's paired t test (alpha=0.05, beta<0.05). Mean (SD) weights were 22.1(2.2) g and 18.4 (2.5) g in the control and experimental groups, respectively, indicating an 18% reduction in the experimental group (p=0.002). Soaking gauze in normal saline heated to 42 degrees C can reduce bleeding after extraction. PMID- 26872899 TI - [Lesbian, gay & grey : Specific needs and concerns of elderly homosexual women and men]. AB - In 2050 society will face the challenge of the effects of demographic changes with approximately 30 % of the Swiss population aged 65 years and older. This change will also lead to a higher number of elderly persons who identify themselves as homosexual and who live together with a same sex partner. In the year 2050 approximately 90,000-300,000 homosexual persons who are 65 years and older will live in Switzerland. This article shows that the current state of research in gerontology is characterized by large gaps regarding homosexuals and research in homosexuality regarding ageing. With a focus on the third and fourth ages of life for homosexuals of both sexes and based on the latest international research data this article shows that elderly homosexual people face specific challenges and have specific needs, which should be taken into account in home care services and nursing homes. Due to their lifestyles elderly homosexuals are often single and live alone, have no biological children and are afraid of being discriminated or stigmatized particularly in the case of their need for nursing. As a further aggravating factor, studies have shown that elderly homosexuals have poorer health conditions than heterosexuals with an increased need for care at an earlier stage in life. PMID- 26872901 TI - AK progressing to NMSC: at what stage? PMID- 26872900 TI - [Mobile geriatric rehabilitation in nursing homes, in short-term care facilities and private homes : Setting-specific analysis of nationwide treatment documentation (Part 2)]. AB - BACKGROUND: Mobile geriatric rehabilitation can be provided in the setting of nursing homes, short-term care (STC) facilities and exclusively in private homes. OBJECTIVE: This study analyzed the common features and differences of mobile rehabilitation interventions in various settings. MATERIAL AND METHODS: Stratified by setting 1,879 anonymized mobile geriatric rehabilitation treatments between 2011 and 2014 from 11 participating institutions were analyzed with respect to patient, process and outcome-related features. RESULTS: Significant differences between the settings nursing home (n = 514, 27 %), STC (n = 167, 9 %) and private homes (n = 1198, 64 %) were evident for mean age (83 years, 83 years and 80 years, respectively), percentage of women (72 %, 64 % and 55 %), degree of dependency on pre-existing care (92 %, 76 % and 64 %), total treatment sessions (TS, 38 TS, 42 TS and 41 TS), treatment duration (54 days, 61 days and 58 days) as well as the Barthel index at the start of rehabilitation (34 points, 39 points and 46 points) and the gain in the Barthel index (15 points, 21 points and 18 points), whereby the gain in the capacity for self-sufficiency was significant in all settings. CONCLUSION: The setting-specific evaluation of mobile geriatric rehabilitation showed differences for relevant patient, process and outcome related features. Compared to inpatient rehabilitation mobile rehabilitation in all settings made an above average contribution to the rehabilitation of patients with pre-existing dependency on care. The gains in the capacity for self sufficiency achieved in all settings support the efficacy of mobile geriatric rehabilitation under the current prerequisites for applicability. PMID- 26872902 TI - Comparison of intra-operative specimen mammography to standard specimen mammography for excision of non-palpable breast lesions: a randomized trial. AB - Standard specimen mammography (SSM) is performed in the radiology department after wire-localized excision of non-palpable breast lesions to confirm the presence of the target and evaluate margins. Alternatively, intra-operative specimen mammography (ISM) allows surgeons to view images in the operating room (OR). We conducted a randomized study comparing ISM and SSM. Women undergoing wire-localized excision for breast malignancy or imaging abnormality were randomized to SSM or ISM. For SSM, the specimen was transported to the radiology department for imaging and interpretation. For ISM, the specimen was imaged in the OR for interpretation by the surgeon and sent for SSM. Interpretation time was from specimen leaving OR until radiologist interpretation for SSM and from placement in ISM device until surgeon interpretation for ISM. Procedure and interpretation times were compared. Concordance between ISM and SSM for target and margins was evaluated. 72 patients were randomized, 36 ISM and 36 SSM. Median procedure times were similar, 48.5 (17-138) min for ISM, and 54 (17-40) min for SSM (p = 0.72), likely since specimens in both groups traveled to radiology for SSM. Median interpretation time was significantly shorter with ISM, 1 (0.5-2.0) and 9 (4-16) min for ISM and SSM, respectively (p < 0.0001). Among specimens with ISM and SSM, concordance was 100 % (35/35) for target and 93 % (14/15) for margins. In this randomized trial, use of ISM compared with SSM significantly reduced interpretation times, while accurately identifying the target. This could result in decreased operative costs from shorter OR times with use of ISM. PMID- 26872904 TI - High-density lipoprotein of patients with breast cancer complicated with type 2 diabetes mellitus promotes cancer cells adhesion to vascular endothelium via ICAM 1 and VCAM-1 upregulation. AB - Adhesion of disseminating tumor cells to vascular endothelium is a pivotal starting point in the metastasis cascade. We have shown previously that diabetic high-density lipoprotein (HDL) has the capability of promoting breast cancer metastasis, and this report summarizes our more recent work studying the role of abnormal HDL in facilitating the adhesion of the circulating tumor cells to the endothelium. This is an initiating step in breast cancer metastasis, and this work assesses the role of ICAM-1 and VCAM-1 in this process. MDA-MB-231, MCF 7, and human umbilical vein endothelial cells (HUVECs) were treated with normal HDL from healthy controls (N-HDL), HDL from breast cancer patients (B-HDL), or HDL from breast cancer patients complicated with type 2 diabetes mellitus (BD-HDL), and the cell adhesion abilities were determined. ICAM-1 and VCAM-1 expression as well as the protein kinase C (PKC) activity were evaluated. The effect of PKC inhibitor and PKC siRNA on adhesion was also studied. The immunohistochemical staining of ICAM-1, VCAM-1, and E-selectin from breast cancer patients and breast cancer patients complicated with type 2 diabetes mellitus (T2DM) were examined. Our results indicate that BD-HDL promoted an increase in breast cancer cell adhesion to HUVECs and stimulated higher ICAM-1 and VCAM-1 expression on the cells surface of both breast cancer and HUVEC cells, along with the activation of PKC. Increased tumor cell (TC)-HUVEC adhesion, as well as ICAM-1 and VCAM-1 expression induced by BD-HDL, could be inhibited by staurosporine and PKC siRNA. In addition, a Db/db type 2 diabetes mouse model has more TC-Vascular Endothelium adhesion compared to a normal model. However, BD patients have a lower expression of ICAM-1, VCAM-1, and E-selectin in their tumor tissues. BD-HDL facilitates the adhesion of tumor cells to vascular endothelium by upregulating the expression of ICAM-1 and VCAM-1, thereby promoting the initial progression of breast cancer metastasis. This work indicates a prospective utilization of HDL-based strategies in the treatment of breast cancer patients with type 2 diabetes. PMID- 26872905 TI - [Erythematosquamous dermatoses in adolescence]. AB - Erythematosquamous dermatoses in adolescents comprise a wide range of differential diagnoses. Age-typical variations of the clinical manifestation, the need to differentiate common conditions from rare diseases as well as the tremendous psychosocial impact which the patients perceive especially in this vulnerable period of life can become major challenges for pediatric dermatologists. This article summarizes key features of common erythematosquamous dermatoses and less frequent skin diseases occurring during adolescence. PMID- 26872903 TI - Healthy dietary patterns and risk of breast cancer by molecular subtype. AB - We examined associations between dietary quality indices and breast cancer risk by molecular subtype among 100,643 women in the prospective Nurses' Health Study (NHS) cohort, followed from 1984 to 2006. Dietary quality scores for the Alternative Healthy Eating Index (AHEI), alternate Mediterranean diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) dietary patterns were calculated from semi-quantitative food frequency questionnaires collected every 2-4 years. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor status from immunostained tumor microarrays in combination with histologic grade. Cox proportional hazards models, adjusted for age and breast cancer risk factors, were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Competing risk analyses were used to assess heterogeneity by subtype. We did not observe any significant associations between the AHEI or aMED dietary patterns and risk of breast cancer by molecular subtype. However, a significantly reduced risk of HER2-type breast cancer was observed among women in 5th versus 1st quintile of the DASH dietary pattern [n = 134 cases, Q5 vs. Q1 HR (95 % CI) = 0.44 (0.25-0.77)], and the inverse trend across quintiles was significant (p trend = 0.02). We did not observe any heterogeneity in associations between AHEI (p het = 0.25), aMED (p het = 0.71), and DASH (p het = 0.12) dietary patterns and breast cancer by subtype. Adherence to the AHEI, aMED, and DASH dietary patterns was not strongly associated with breast cancer molecular subtypes. PMID- 26872906 TI - Linezolid-induced optic neuropathy with a rare pathological change in the inner retina. AB - We report a case of linezolid-induced optic neuropathy with transient microcystic spaces in the inner retina. We observed the retina using Fourier-domain optical coherence tomography (FD-OCT) in a patient with linezolid-induced optic neuropathy. A 49-year-old woman presented to our department with a 1-week history of bilateral photophobia. At the first visit, her best-corrected visual acuity (VA) was 0.6 in the right eye and 0.5 in the left eye. She had moderate optic disk edema and central scotomas bilaterally. FD-OCT showed bilateral microcystic spaces in the retina. Microcystic spaces were seen in the retinal nerve fiber layer (RNFL) and at the border of the RNFL and the retinal ganglion cell layer. Magnetic resonance imaging and laboratory tests showed no positive findings except for an elevated lactic acid level. One week after the first visit, the VA levels decreased to 0.06 and 0.07 in the right and left eyes, respectively. Because the patient had a 7-month history of linezolid treatment for persistent pyogenic arthritis, we suspected linezolid-induced optic neuropathy and immediately terminated treatment with this drug. The optic disk edema and the microcystic spaces in the retina resolved, and the VA improved to 1.2 at 6 weeks after linezolid withdrawal. Microcystic spaces, which resolved with linezolid withdrawal, were observed in linezolid-induced optic neuropathy. The microcystic spaces in the inner retina can be the first retinal sign of some optic neuropathies. PMID- 26872907 TI - Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. AB - Inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of rare hematological disorders characterized by the impairment of hematopoiesis, which harbor specific clinical presentations and pathogenic mechanisms. Some of these syndromes may progress through clonal evolution, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Most prominent are failures of DNA repair such as Fanconi Anemia and much rarer failure of ribosomal apparatus, e.g., Diamond Blackfan Anemia or of telomere elongation such as dyskeratosis congenita. In these congenital disorders, hematopoietic stem cell transplantation (HSCT) is often a consideration. However, HSCT will not correct the underlying disease and possible co-existing extra-medullary (multi)-organ defects, but will improve BMF. Indications as well as transplantation characteristics are most of the time controversial in this setting because of the rarity of reported cases. The present paper proposes a short overview of current practices. PMID- 26872908 TI - Comparison of myocardial T1 and T2 values in 3 T with T2* in 1.5 T in patients with iron overload and controls. AB - Myocardial iron quantification remains limited to 1.5 T systems with T2* measurement. The present study aimed at comparing myocardial T2* values at 1.5 T to T1 and T2 mapping at 3.0 T in patients with iron overload and healthy controls. A total of 17 normal volunteers and seven patients with a history of myocardial iron overload were prospectively enrolled. Mid-interventricular septum T2*, native T1 and T2 times were quantified on the same day, using a multi-echo gradient-echo sequence at 1.5 T and T1 and T2 mapping sequences at 3.0 T, respectively. Subjects with myocardial iron overload (T2* < 20 ms) in comparison with those without had significantly lower mean myocardial T1 times (868.9 +/- 120.2 vs. 1170.3 +/- 25.0 ms P = 0.005 respectively) and T2 times (34.9 +/- 4.7 vs. 45.1 +/- 2.0 ms P = 0.007 respectively). 3 T T1 and T2 times strongly correlated with 1.5 T, T2* times (Pearson's r = 0.95 and 0.91 respectively). T1 and T2 measures presented less variability than T2* in inter- and intra-observer analysis. Native myocardial T1 and T2 times at 3 T correlate closely with T2* times at 1.5 T and may be useful for myocardial iron overload quantification. PMID- 26872910 TI - Evidence That COG0325 Proteins are involved in PLP Homeostasis. AB - Pyridoxal 5'-phosphate (PLP) is an essential cofactor for nearly 60 Escherichia coli enzymes but is a highly reactive molecule that is toxic in its free form. How PLP levels are regulated and how PLP is delivered to target enzymes are still open questions. The COG0325 protein family belongs to the fold-type III class of PLP enzymes and binds PLP but has no known biochemical activity although it occurs in all kingdoms of life. Various pleiotropic phenotypes of the Escherichia coli COG0325 (yggS) mutant have been reported, some of which were reproduced and extended in this study. Comparative genomic, genetic and metabolic analyses suggest that these phenotypes reflect an imbalance in pyridoxal 5'-phosphate (PLP) homeostasis. The E. coli yggS mutant accumulates the PLP precursor pyridoxine 5'-phosphate (PNP), and is sensitive to an excess of pyridoxine but not of pyridoxal. The pyridoxine toxicity phenotype is complemented by the expression of eukaryotic yggS orthologs. It is also suppressed by the presence of amino acids specifically isoleucine, threonine and leucine suggesting the PLP dependent enzyme transaminase B (IlvE) is affected. These genetic results lay a foundation for future biochemical studies of the role of COG0325 proteins in PLP homeostasis. PMID- 26872909 TI - Fibrin-related markers for diagnosing acute-, subclinical-, and pre-venous thromboembolism in patients with major orthopedic surgery. AB - Venous thromboembolism (VTE) is a common complication in patients who have undergone major orthopedic surgery, but there are few predictors of VTE after major orthopedic surgery treated with an anticoagulant. We measured levels of fibrin-related markers (FRMs), such as D-dimer, soluble fibrin (SF), and fibrinogen and fibrin degradation products (FDPs) in 66 patients with acute-phase VTE, and 367 patients undergoing major orthopedic surgery. Plasma FDP, D-dimer, and SF levels were significantly higher in patients with acute VTE, but only FDP and D-dimer levels were significantly higher in subclinical VTE. Adequate cut-off levels of D-dimer were 2.2 MUg/ml for diagnosing acute VTE and 1.5 MUg/ml for diagnosing subclinical VTE. D-dimer of less than 1.9 or 0.7 MUg/ml ruled out acute VTE or subclinical VTE. D-dimer of more than 1.3 MUg/ml preoperatively showed a moderate risk for postoperative VTE. Measurement of FRMs is useful for evaluating the risk of subclinical or postoperative VTE in patients with major orthopedic surgery. In particular, FDP is the most valuable marker for diagnosing acute VTE, whereas D-dimer is the most valuable for diagnosing subclinical VTE or predicting VTE. PMID- 26872911 TI - Patient-reported outcome measures for cancer caregivers: a systematic review. AB - PURPOSE: Informal caregivers provide invaluable help and support to people with cancer. As treatments extend survival and the potential burdens on carers increase, there is a need to assess the impact of the role. This systematic review identified instruments that measure the impact of caregiving, evaluated their psychometric performance specifically in cancer and appraised the content. METHODS: A two-stage search strategy was employed to: (1) identify instruments that measure the impact of caregiving, and (2) run individual searches on each measure to identify publications evaluating psychometric performance in the target population. Searches were conducted in MEDLINE, EMBASE, CINAHL and PsycINFO and restricted to English for instrument used and article language. Psychometric performance was evaluated for content and construct validity, internal consistency, test-retest reliability, precision, responsiveness and acceptability. Individual scale items were extracted and systematically categorised into conceptual domains. RESULTS: Ten papers were included reporting on the psychometric properties of eight measures. Although construct validity and internal consistency were most frequently evaluated, no study comprehensively evaluated all relevant properties. Few studies met our inclusion criteria so it was not possible to consider the psychometric performance of the measures across a group of studies. Content analysis resulted in 16 domains with 5 overarching themes: lifestyle disruption; well-being; health of the caregiver; managing the situation and relationships. CONCLUSIONS: Few measures of caregiver impact have been subject to psychometric evaluation in cancer caregivers. Those that have do not capture well changes in roles and responsibilities within the family and career, indicating the need for a new instrument. PMID- 26872912 TI - Known-groups validity of the Patient-Reported Outcomes Measurement Information System (PROMIS((r))) in adolescents and young adults with special healthcare needs. AB - PURPOSE: To examine known-groups validity of the Patient-Reported Outcomes Measurement Information System (PROMIS((r))) Short Forms (SFs) for adolescents and young adults with special healthcare needs (SHCN) using data collected from the PROMIS Linking Study. METHODS: In total, 292 adolescents aged 14-17.9 years and 300 young adults aged 18-20 years with SHCN from the PROMIS Linking Study were used for analyses. Presence of SHCN was classified into three categories (medication use, service use, and functional limitations). HRQoL was measured with the PROMIS Pediatric and Adult SFs. Differences in health-related quality of life (HRQoL) domain scores between SHCN sample and the norms of the PROMIS pediatric and adult calibration samples, respectively, were compared using t tests. Associations of HRQoL scores with the presence of individual SHCN categories were tested using linear regression. RESULTS: All HRQoL domain scores for the SHCN samples were significantly worse than the respective calibration samples. Adolescents and young adults with SHCN-related service use and functional limitations reported worse HRQoL than those without service use and functional limitations (p's < 0.01). CONCLUSIONS: PROMIS Pediatric and Adult SFs possess satisfactory known-groups validity related to SHCN status. PMID- 26872913 TI - Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. PMID- 26872914 TI - CORR Insights(r): How Much Clinical and Functional Impairment do Children Treated With Knee Rotationplasty Experience in Adulthood? PMID- 26872915 TI - From Bench to Bedside: Targeted Therapy, Denosumab, and 21st Century Orthopaedics: Targets Abound, But Where Are The Therapies? PMID- 26872916 TI - The zebrafish fast myosin light chain mylpfa:H2B-GFP transgene is a useful tool for in vivo imaging of myocyte fusion in the vertebrate embryo. AB - BACKGROUND: Skeletal muscle fibers are multinucleated syncytia that arise from the fusion of mononucleated precursors, the myocytes, during embryonic development, muscle hypertrophy in post-embryonic growth and muscle regeneration after injury. Even though myocyte fusion is central to skeletal muscle differentiation, our current knowledge of the molecular mechanism of myocyte fusion in the vertebrates is rather limited. Previous work, from our group and others, has shown that the zebrafish embryo is a very useful model for investigating the cell biology and genetics of vertebrate myocyte fusion in vivo. RESULTS: Here, we report the generation of a stable transgenic zebrafish strain that expresses the Histone 2B-GFP (H2B-GFP) fusion protein in the nuclei of all fast-twitch muscle fibers under the control of the fast-twitch muscle-specific myosin light chain, phosphorylatable, fast skeletal muscle a (mylpfa) gene promoter. By introducing this transgene into a mutant for junctional adhesion molecule 3b (jam3b), which encodes a cell adhesion protein previously implicated in myocyte fusion, we demonstrate the feasibility of using this transgene for the analysis of myocyte fusion during the differentiation of the trunk musculature of the zebrafish embryo. CONCLUSIONS: Since we know so little about the molecules regulating vertebrate myocyte fusion, we propose that the mylpfa:H2B-GFP transgene will be a very useful reporter for conducting forward and reverse genetic screens to identify new components regulating vertebrate myocyte fusion. PMID- 26872917 TI - Pulmonary rehabilitation: the next steps. PMID- 26872920 TI - Efficacy of treatment of elevated coccidial oocyst counts in goats using amprolium versus ponazuril. AB - Coccidiosis is an important disease of young goats leading to weight loss, diarrhea, and death. In the USA, both ionophores and decoquinate are labeled for prevention of coccidia in goats. However, there are no drugs approved for treatment of clinical cases of coccidiosis in this species. Amprolium is labeled for treatment of coccidiosis in calves while ponazuril, a metabolite of toltrazuril, is labeled for treatment of equine protozoal myeloencephalitis. In this study, 150 young goats housed on concrete lots had fecal samples collected and McMaster fecal oocyst per gram counts performed at 0, 7, 14, and 21 days post processing. Goats were randomly assigned to receive either amprolium (50mg/kg once a day for 5 days by mouth) or ponazuril (10mg/kg by mouth once) if they had fecal oocyst counts >5,000 per gram. Fecal samples were obtained and oocyst counts performed at days 7, 14, 21, and 28 after the cessation of treatment. Goats were weighed on days 0 and 21 post-processing. Seven goats were enrolled into the amprolium group and 8 into the ponazuril group. Both treatments resulted in decreased oocyst counts post-treatment compared to before treatment. There was no significant difference between fecal coccidian oocyst counts between goats in each group. There was no significant difference in body weight between goats in each group. This study showed that both amprolium and ponazuril were effective in decreasing fecal coccidia oocyst counts in this group of goats. Use of both drugs is currently extra-label in the USA. PMID- 26872918 TI - The effectiveness of pharmacological agents for the treatment of uveitic macular oedema (UMO): a systematic review protocol. AB - BACKGROUND: Macular oedema (MO) describes the accumulation of fluid in the central part of the retina, known as the 'macula' which provides central vision. MO is the leading cause of sight loss in patients with intraocular inflammation (uveitis). There is a lack of consensus over the treatment of uveitic macular oedema (UMO). The proposed systematic review will evaluate the evidence on the effectiveness of pharmacological agents used to treat UMO. All systemic, local, or topical pharmacological agents will be included. METHOD/DESIGN: Standard systematic review methodology will be employed to identify, select and extract data from comparative studies (randomised/non-randomised trials and observational studies) of the pharmacological interventions in patients with UMO. Searches will be conducted through bibliographic databases (Cochrane Library, MEDLINE, EMBASE and CINAHL) and clinical trials registers. No restriction will be placed on either language or year of publication. Translation of non-English language articles will be undertaken to minimise selection bias. The primary outcome of interest will be best corrected visual acuity and secondary outcomes will be adverse events, health-related quality of life, assessment of UMO using central macular thickness (e.g. by optical coherence topography (OCT)), clinical and angiographic assessment of UMO, clinical estimation of vitreous haze. Risk of bias assessment appropriate to each study design will be undertaken. Data will be grouped by comparison, tabulated and narratively synthesised. Meta-analysis will be undertaken where clinical and methodological homogeneity exists. Subgroup and sensitivity analyses, also network analyses and intra/inter-pharmacological class analyses will be undertaken where deemed appropriate. DISCUSSION: A number of published studies have investigated the effectiveness of the pharmacological agents used to treat UMO. However, there is no recent systematic review that synthesises this evidence. This systematic review will analyse the effectiveness of systemic, local and topical therapies to treat UMO. The findings will provide important evidence to inform clinical and health policy decision-making for the treatment of UMO. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42015019170. PMID- 26872921 TI - Association between variation in faecal egg count for a natural mixed field challenge of nematode parasites and TLR4 variation. AB - Research has shown that Toll-like receptor 4 (TLR4) is important in immune responses to some helminth parasites. In sheep, variation in the PAMP region of TLR4 may result in structurally and thus functionally different TLR4 molecules, and this may consequently lead to variation in the TLR4 response to parasite infections. This study involved three separate, but related sheep breeds (Merino, Polwarth and Corriedale sheep) and a total of 885 lambs from five New Zealand farms that underwent a mixed field-challenge from gastro-intestinal parasites. Faecal samples were collected at approximately 4 and 9 months of age and faecal egg counts (FECs) for Nematodirus spp. and Strongyle species determined, along with the total number of eggs per gram (EPG). Analysis of the five farms collectively revealed an association (P=0.023) between the presence of TLR4 variant *02 (mean 24 EPG) and the absence of the variant (mean 32 EPG) at 9 months of age. Conversely the presence of *03 had a significantly (P=0.047) higher mean Nematodirus spp. FEC (mean 42 EPG) compared to the absence (mean 28 EPG) at 9 months of age. More associations were revealed when the data were split according to the dominant faecal parasite species. With a predominantly Trichostrongylus spp. FEC group of lambs at 9 months of age, the presence of TLR4 variant *02 was found to have significantly (P=0.003) lower Nematodirus spp. FEC (mean 4 EPG), and also significantly (P=0.033) lower total FEC (mean 312 EPG) when compared to sheep without the variant (mean 15 EPG and 449 EPG, respectively). The presence of TLR4 variant *03 and *04 were associated or tended to be associated (P=0.010 and P=0.088, respectively) with higher Nematodirus spp. FEC (mean 25 EPG and 22 EPG, respectively) when compared to lambs without the variant (mean 10 EPG and 11 EPG, respectively). These results suggest that TLR4 variation may be affecting the immune response to gastro-intestinal parasites in sheep, although principally to Nematodirus spp. infections and not Strongyle species infections. PMID- 26872919 TI - Prediabetes, undiagnosed diabetes, and diabetes among Mexican adults: findings from the Mexican Health and Aging Study. AB - PURPOSE: The purpose of the study was to examine the prevalence and determinants of prediabetes, undiagnosed diabetes, and diabetes among Mexican adults from a subsample of the Mexican Health and Aging Study. METHODS: We examined 2012 participants from a subsample of the Mexican Health and Aging Study. Measures included sociodemographic characteristics, body mass index, central obesity, medical conditions, cholesterol, high-density lipoprotein cholesterol, hemoglobin A1c, and vitamin D. Logistic regression was performed to identify factors associated with prediabetes, undiagnosed diabetes, and self-reported diabetes. RESULTS: Prevalence of prediabetes, undiagnosed, and self-reported diabetes in this cohort was 44.2%, 18.0%, and 21.4%, respectively. Participants with high waist-hip ratio (1.61, 95% confidence interval [CI] = 1.05-2.45) and high cholesterol (1.85, 95% CI = 1.36-2.51) had higher odds of prediabetes. Overweight (1.68, 95% CI = 1.07-2.64), obesity (2.38, 95% CI = 1.41-4.02), and high waist circumference (1.60, 95% CI = 1.06-2.40) were significantly associated with higher odds of having undiagnosed diabetes. Those residing in a Mexican state with high U.S. migration had lower odds of prediabetes (0.61, 95% CI = 0.45-0.82) and undiagnosed diabetes (0.53, 95% CI = 0.41-0.70). Those engaged in regular physical activity had lower odds of undiagnosed diabetes (0.74, 95% CI = 0.57 0.97). CONCLUSIONS: There is a high prevalence of prediabetes and undiagnosed diabetes among Mexican adults in this subsample. Findings suggest the need for resources to prevent, identify, and treat persons with prediabetes and undiagnosed diabetes. PMID- 26872923 TI - Scavenging hagfish as a transport host of Anisakid nematodes. AB - Hagfish are the most primitive craniates and scavengers, feeding on dead organisms as well as fish and invertebrates. Hagfish play an important ecological role in recycling nutrients, helping to recycle biomass from the upper water column. We investigated 265 specimens of four hagfish species, including Eptatretus burgeri, Eptatretus yangi, Eptatretus sheni and Eptatretus taiwanae from northeastern Taiwanese waters of the northwestern Pacific from November 2013 to June 2014. Eight species of Anisakid nematodes were identified: Anisakis pegreffii, Anisakis simplex s.s., a recombinant genotype of A. pegreffii and A. simplex s.s., Anisakis typica, Anisakis sp., Anisakis brevispiculata, Anisakis physeteris and Hysterothylacium amoyense. Anisakis sp. and H. amoyense represented new locality records. The prevalence, mean intensity and mean abundance of anisakid nematodes for all specimens were 21.51%, 5.39 larvae per fish and 1.16 larvae per fish, respectively. A. pegreffii was the most frequent species in E. burgeri, E. yangi and E. taiwanae, whereas in E. sheni, the dominant species was Anisakis sp. The number of nematodes was significantly related to the host length for E. burgeri and E. sheni, but was not related to the sex of the four hagfish species. This report of scavenging hagfish infected with Anisakid larvae suggests hagfish as a transport/paratenic host between cetaceans and piscivores. Anisakiasis may be caused by the consumption of infectious third-stage larvae in raw or undercooked hagfish. PMID- 26872922 TI - Fatal echinococcosis in three lemurs in the United Kingdom--A case series. AB - Tapeworms of the genus Echinococcus reside in the small intestine of a number of carnivorous species, predominantly canids. In enzootic areas, hydatidosis caused by taeniid metacestodes can present a significant problem in accidental intermediate hosts, including humans. Whereas the United Kingdom is currently considered free of Echinococcus multilocularis, Echinococcus granulosus sensu stricto (s.s.) and Echinococcus equinus are endemic in the UK and have been reported in a variety of captive mammals. The presentation of echinoccocosis in non-human primates widely parallels disease in humans, and public health concerns are related to the four genera, E. granulosus, E. multilocularis, Echinococcus vogeli and Echinococcus oligarthrus. In contrast, sporadic outbreaks and individual hydatid disease cases in non-human primates have been associated with several Echinococcus and Taenia species. Here we describe three fatal cases of cystic echinococcosis in two captive ring-tailed lemurs (Lemur catta) and one captive red-ruffed lemur (Varecia variegata rubra) and provide molecular tapeworm characterisation. To the best of the authors' knowledge, this includes the first report of Echinococcus ortleppi in a UK born ring-tailed lemur and provides the first in depth case reports of echinococcosis due to E. equinus in UK born ring tailed and red ruffed lemurs with detailed clinical and pathological findings. The cestode life cycle and implications for zoo collections are discussed. PMID- 26872924 TI - Viability of the Happy FactorTM targeted selective treatment approach on several sheep farms in Scotland. AB - The aim of this study was to examine the use of Happy FactorTM weight based targeted selective treatment (TST) on several commercial farms in Scotland in combination with findings from a long term trial on a research farm to assess the potential for TST use in varying farming operations as an alternative to the current regimen of whole flock treatment. Lambs on each farm were regularly weighed and climatic conditions and pasture availability measured for inclusion into the Happy FactorTM model to calculate weight targets. Half of the lambs were allocated to TST treatment and any failing to reach the weight target was treated with the anthelmintic of choice on that farm, while the remaining half of each flock was treated with anthelmintic as per normal practice on that farm (routine treatment, RT). The research farm (farm 1) hosted a long term trial using four anthelmintic treatment regimes over 6 years, and data from two regimes are presented here, alongside findings from three further farms: two commercial enterprises (farms 2 and 3) and a research farm operating as a commercial analogue with two breeds (farms 4a and 4b). The effect of TST strategy on lamb productivity and the number of anthelmintic treatments was investigated. There was no evidence (p>0.300) that mean bodyweight or growth rate was different between TST and RT groups on any of the farms and 95% confidence intervals of TST and RT groups generally suggested that TST had negligible unfavourable effects on the average growth of lambs for most of the farms. Growth rates ranged from 97.39 to 189.16g/day reflecting the varied nature of the farms. All commercial farms used significantly less (1.34 RT versus 1.14 TST treatments per animal, p<0.05) anthelmintic in lambs following TST, with a reduction from 1, 1, 1.03 and 1.14 to 0.77, 0.57, 0.82 and 0.81 in the number of treatments per animal for farms 2, 3, 4a and 4b respectively. This study suggests that TST is a viable means of controlling parasitic disease without incurring production losses. PMID- 26872925 TI - Serodiagnosis of bovine trypanosomosis caused by non-tsetse transmitted Trypanosoma (Duttonella) vivax parasites using the soluble form of a Trypanozoon variant surface glycoprotein antigen. AB - Previous studies have shown that a 64-kDa antigen (p64) that was purified from the Venezuelan TeAp-N/D1 isolate of Trypanosoma (Trypanozoon) equiperdum corresponds to the soluble form of its predominant variant surface glycoprotein (VSG), and exhibited cross-reactivity with Trypanosoma (Duttonella) vivax. The course of experimental acute infections of bovines with T. vivax were followed by measuring whole anti-p64 antibodies and specific anti-p64 IgG and IgM antibodies in animal sera by indirect enzyme-linked immunosorbent assay (ELISA). The value of p64 to diagnose bovine trypanosomosis was also examined using 350 sera from healthy and T. vivax-infected cows living in a trypanosomosis-endemic and enzootic stable area, and 48 sera obtained during a trypanosomosis outbreak. Serological assays showed that ~ 70-80% of the infected sera contained anti-p64 antibodies, based on the comparative immunodetection of the T. equiperdum clarified antigenic fraction used as a reference test. In the absence of a gold standard, Bayesian analysis for multiple testing estimated a sensitivity and specificity of 71.6% and 98.8%, respectively, for the indirect ELISA using p64 as antigen. An apparent prevalence of 37.7% for bovine trypanosomosis infection was also estimated with a Bayesian approach when the p64 ELISA test was used. Employing blood from acute infected cows, the indirect ELISA response against p64 was contrasted with the microhematocrit centrifuge method and analyses by polymerase chain reaction (PCR) using specific primers targeting the inter specific length variation of the internal transcribed spacer 1 region of the 18S ribosomal gene. The efficiency of p64 for the detection of anti-trypanosome antibodies in acute infected bovines was also corroborated serologically by comparing its response to that of the Indonesian Trypanosoma evansi Rode Trypanozoon antigen type (RoTat) 1.2 VSG, which possesses high specificity and sensitivity. As expected, PCR was the best method to detect parasites and diagnose bovine trypanosomosis; however, a substantial level of concordance (Cohen's kappa=0.667) was obtained when serological tests using p64 and RoTat 1.2 VSG were compared. Additionally, an agglutination assay was designed using p64 covalently coupled to carboxylate-modified latex microparticles, which was proven here to be suitable for a fast qualitative diagnosis of bovine trypanosomosis. PMID- 26872926 TI - Proteomics analysis of Echinococcus granulosus protoscolex stage. AB - Echinococcus granulosus protoscolex proteins were separated using two-dimensional electrophoresis and then identified using mass spectrometry; we identified 61 proteins, 28 which are newly described of which 4 could be involved in hydatid cyst fertility molecular mechanisms. PMID- 26872927 TI - Neospora caninum is the leading cause of bovine fetal loss in British Columbia, Canada. AB - The protozoan pathogen Neospora caninum is recognized as a leading cause of infectious abortions in cattle worldwide. To evaluate the impact of neosporosis on dairy and beef herd production, a retrospective, longitudinal study was performed to identify the impact of neosporosis alongside other causes of fetal abortion in British Columbia, Canada. Retrospective analysis of pathology records of bovine fetal submissions submitted to the Animal Health Centre, Abbotsford, British Columbia, a provincial veterinary diagnostic laboratory, from January 2007 to July 2013 identified 182 abortion cases (passive surveillance). From July 2013 to May 2014, an active surveillance program identified a further 54 abortion cases from dairy farmers in the Upper Fraser Valley, British Columbia. Of the total 236 fetal submissions analyzed, N. caninum was diagnosed in 18.2% of cases, making it the most commonly identified infectious agent associated with fetal loss. During active surveillance, N. caninum was associated with 41% of fetuses submitted compared to 13.3% during passive surveillance (p<0.001). Breed of dam was significantly associated with N. caninum diagnosis, with a higher prevalence in dairy versus beef breeds, and fetuses of 3-6 months gestational age had the highest prevalence of N. caninum. There was no significant association with dam parity. N. caninum was diagnosed in every year except 2009 and cases were geographically widespread throughout the province. Furthermore, the active surveillance program demonstrates that N. caninum is highly prevalent in the Upper Fraser Valley and is a major causal agent of production losses in this dairy intensive region. PMID- 26872928 TI - Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice. AB - Carvacrol is a compound isolated from some essential oils. It has been reported to possess anthelmintic activity. Acetylation of this monoterpene has been proposed as a potential way to reduce the toxicity and enhance the pharmacological effects of carvacrol. This study aimed to evaluate the effect of carvacryl acetate (CA) using in vitro and in vivo assays with gastrointestinal nematodes of small ruminants. The egg hatching test (EHT), larval development test (LDT) and adult worm motility (AWM) assessment were conducted to evaluate the effect of the acetylated product and pure carvacrol on Haemonchus contortus eggs, larvae and adults. The structural changes induced in adult H. contortus were assessed using scanning electron microscopy (SEM). CA and carvacrol acute toxicity was evaluated in mice. Finally, the efficacy of 250 mg/kg CA and 2.5mg/kg monepantel (positive control) were evaluated in 30 sheep naturally infected with gastrointestinal nematodes by the fecal egg count reduction test (FECRT). In vitro tests were analyzed by analysis of variance (ANOVA) followed by comparison with Tukey's test. The efficacy was calculated by the Boot Street program using the arithmetic average. The number of eggs in feces (epg) of the groups were transformed to log (x+1) and subjected to ANOVA to compare differences among the groups by Tukey's test. The level of significance was P<0.05. CA and carvacrol inhibited larval hatching by 89.3 and 97.7% at doses of 8.0 and 1.0mg/ml, respectively. At the concentration of 2mg/ml, CA and carvacrol inhibited 100% of larval development. At a concentration of 200 MUg/ml, CA and carvacrol inhibited the motility of adult worms by 100% and 58.3% at 24h post exposure, respectively. CA caused cuticle and vulvar flap wrinkling and bubbles to emerge from the tegument. Carvacrol caused more discreet effects on the cuticle and vulvar flap. The LD10 and LD50 of CA were 566.7 mg/kg and 1544.5mg/kg, respectively. The LD10 and LD50 of carvacrol were 546.8 mg/kg and 919 mg/kg, respectively. CA and monepantel reduced the epg of sheep by 65.9 and 96.4%, respectively, at 16 days post-treatment. CA showed in vitro and in vivo anthelmintic activity and was less toxic than carvacrol. PMID- 26872929 TI - An observational study of the vertical transmission of Theileria orientalis (Ikeda) in a New Zealand pastoral dairy herd. AB - Although only recently recognised, Theileria orientalis (Ikeda) is now the most important infectious cause of anaemia in New Zealand cattle. The aim of this study was to test if vertical transmission of T. orientalis (Ikeda) from dam to calf across the placenta occurs in naturally infected New Zealand dairy cattle and to also test whether the infection status of the dam at calving affects the future susceptibility of its offspring to T. orientalis (Ikeda) infection. Dairy cows (n=97) and their calves were sampled at calving; and the calves again at 4 months of age. All samples were measured for haematocrit and screened for T. orientalis genotypes using a multiplex Buffeli, Chitose and Ikeda specific TaqMan assay. Ikeda positive samples were further tested by singleplex PCR in triplicate to calculate the Ikeda infection intensity as genomes/MUl of blood from each infected animal. No T. orientalis (Ikeda) infected calves were born to either T. orientalis (Ikeda) infected or uninfected dams. There were 56/97 dams positive for T. orientalis (Ikeda) infection at calving and 79/90 calves positive for T. orientalis (Ikeda) infection at 4 months of age but no effect on calf susceptibility of dam infection status at calving. There was a significant negative effect of infection intensity on haematocrit after controlling for whether the infected animal was a dam or a 4 month old calf. Vertical trans uterine transmission of T. orientalis (Ikeda) infection is unlikely in chronically infected dairy cows and thus not a factor in the epidemiology of T. orientalis (Ikeda) infection. PMID- 26872930 TI - The efficacy of flubendazole against different developmental stages of the poultry roundworm Ascaridia galli in laying hens. AB - Infection with the poultry roundworm Ascaridia galli has increased in European countries due to the ban on battery cages. This study was conducted in two commercial laying hen flocks (F1 & F2) on different farms in central Sweden. The aims were to (1) investigate the efficacy of flubendazole (FLBZ, 1.43 mg/kg administered in drinking water for 7 days) against adult and larval stages including histotrophic larvae of A. galli, and (2) determine how long it took before the flocks were reinfected after deworming. Accordingly, 180 randomly selected hens were sacrificed before drug administration (bd), on day 3 and 7 during drug administration (dd), and on a weekly basis for up to five weeks post drug administration (pd). Intestinal contents and cloacal materials of each hen plus pooled faecal samples from manure belts were investigated to assess the worm burden and the parasite egg per gram faeces (epg). Additionally, drinking water, and serum and gastrointestinal digesta content samples obtained from ten treated animals were analyzed by HPLC to measure FLBZ and its reduced (R-FLBZ) and hydrolyzed (H-FLBZ) metabolites. No parasite eggs were observed in cloacal samples on day 21 and 28 pd on F1 and on day 21 pd on F2. The epg in manure decreased by 65% and 88% on day 3 dd and by 99% and 97% on day 35 pd on F1 and F2 respectively. Mean FLBZ concentrations quantified in duodenal contents ranged between 0.50 and 0.79 MUg/g. Although, no histotrophic larvae were found dd, they reappeared one week pd (7 +/- 7 F1, 0.5 +/- 0.5 F2). Adult worms were found in both flocks before drug administration (44 +/- 20 F1, 35 +/- 25 F2), on day 3 dd (4 +/- 3 F1, 2 +/- 2 F2), and then not until day 35 (0.2 +/- 0.6) on F1 and day 28 (0.4 +/- 0.9) pd on F2. Thus, the only period in which no A. galli were found was on day 7 dd. Although FLBZ was highly efficient our results indicate that the birds were reinfected already within one week pd. PMID- 26872931 TI - Mange mite infestation in small ruminants in Ethiopia: Systematic review and meta analysis. AB - Mange mites are economically important ectoparasites of sheep and goats responsible for rejection or downgrading of skins in tanneries or leather industries in Ethiopia. The objective of this systematic review was to compute the pooled prevalence estimate and identify factors influencing mange mite prevalence in sheep and goats at national level based on the available research evidence. Articles on mange mite infestation of small ruminants in Ethiopia were searched in PubMed, Web of Science, Google scholar and African journals on-line. The review was based on 18 cross-sectional studies carried out between 2003 and 2015 in four administrative states of Ethiopia. Accordingly, the pooled prevalence estimate in a random effects meta-analysis was estimated to be 4.4% (95% CI 3.0, 6.3) although there were evidence of a substantial amount of between study variance (I(2)=98.4%). In subgroup and multivariable meta-regression analyses, animal species, agro-ecology and administrative state were found to have significant effect on the prevalence estimate (P<0.05) and explained 32.87% of the explainable proportion of the heterogeneity noted between studies The prevalence was found to be higher in goats in lowland agro-ecology. Region wise the highest estimate was calculated for Amhara (6.4%) followed by Oromia (4.7%), Tigray (3.6%) and Southern Nations, Nationalities and People Region (SNNPR) (3.1%). Significant difference was noted between Amhara and SNNPR. The study further revealed that mites of the genus Sarcoptes, Demodex and Psoroptes are the most prevalent mites infesting small ruminants in Ethiopia. Valid studies were lacking from five regional states. As some of these regions are known for their large small ruminant population, further studies are warranted to produce better picture of the infestation at a national level. Meanwhile, the need for monitoring the ongoing control intervention is suggested. PMID- 26872932 TI - An outbreak of bovine meningoencephalomyelitis with identification of Halicephalobus gingivalis. AB - Halicephalobus gingivalis is an opportunistic parasite which is known to cause fatal meningoencephalomyelitis primarily in equines but sporadically also in humans. In April 2014, laboratory examination of the head of a young dairy calf, euthanized due to severe central nervous system symptoms, revealed the presence of granulomatous to necrotizing encephalitis and myriads of nematodes in the brain lesion. Morphologically the parasites were identified as H. gingivalis. The diagnosis was confirmed by molecular analysis of the large subunit (LSU) rRNA and the small subunit (SSU) rRNA genes, revealing genetic variations of 0.5-4.4% and 0.7-8.6%, respectively, between the H. gingivalis isolated from the Danish calf and published isolates, collected worldwide from free-living and parasitic stages of the nematode. Clinical symptoms and histological changes indicated infection with H. gingivalis from another three calves in the herd. This is the first scientific publication of H. gingivalis induced meningoencephalomyelitis in ruminants. As ante mortem diagnosis is a major challenge, the infection may easily remain undiagnosed in cattle. PMID- 26872934 TI - Benzimidazole resistance in equine cyathostomins in India. AB - Benzimidazole resistance is a major hindrance to the control of equine cyathostominosis throughout the world. There is a paucity of knowledge on the level of benzimidazole resistance in small strongyles of horses in India. In the present study, allele-specific PCR (AS-PCR) that detects F200Y mutation of the isotype 1 beta-tubulin gene and faecal egg count reduction test (FECRT) were used for detecting benzimidazole resistance in equine cyathostomin populations in different agro-climatic zones of Uttar Pradesh, India. Results of the FECRT revealed prevalence of benzimidazole resistance in cyathostomins in an intensively managed equine farm in the mid-western plain (FECR=27.5%, LCI=0) and in working horses (extensively managed) at three locations in central plains of Uttar Pradesh (FECR=75.7-83.6%, LCI=29-57%). Post-treatment larval cultures revealed the presence of exclusively cyathostomin larvae. Genotyping of cyathostomin larvae by AS-PCR revealed that the frequency of homozygous resistant (rr) individuals and the resistant allele frequency was significantly higher (p<0.001) in the intensively managed farm in the mid-western plain and in working horses at two locations in central plains of the state. The resistant allele (r) frequency in cyathostomins was significantly higher (p<0.05) in Vindhyan and Tarai and Bhabar zones of Uttar Pradesh. The prevalence of benzimidazole resistant allele (r) was significantly higher (p<0.05) in cyathostomins of intensively managed horses (allelic frequency-0.35) as compared to extensively managed horses (allelic frequency-0.22). The widespread prevalence of benzimidazole resistant alleles in equine cyathostomins in Uttar Pradesh, India, necessitates immediate replacement of the drugs of benzimidazole group with other unrelated effective anthelmintics for management and control of equine cyathostomins. PMID- 26872933 TI - Impact of the post-weaning nutritional history on the response to an experimental Haemonchus contortus infection in Creole goats and Black Belly sheep. AB - In small ruminants, the response against gastrointestinal nematode (GIN) infections is influenced not only by the host genotype and the physiological stage but also by environmental factors, particularly the nutritional status at the time of infection. In this study we evaluated the long-term effect and the interaction between the host species and the nutritional history on the response to GIN infection in two animal models differing in their phenotypic growth and their level of GIN resistance: Black Belly sheep and Creole goats. Lambs and kids were subjected to three distinct nutritional conditions at weaning: low dietary conditions (100% of the theoretical energy requirement for maintenance, corresponding to 548v. 484KJ/Kg BW(0.75) for lambs and kids respectively and 6% of crude protein, CP), medium dietary conditions (150% of the theoretical energy requirement for maintenance and 13% CP) and high dietary conditions (200% of the theoretical energy requirement for maintenance and 20% CP). This 3-months period was followed by a 1-month period on the medium dietary conditions for all the animals before an experimental Haemonchus contortus infection. We monitored the impact of the nutritional history (nutritional condition after weaning), on the intensity of the GIN infection by measuring individual faecal egg counts (FEC), growth rate (ADG), blood eosinophil counts and other pathophysiological parameters. The FEC, growth rate and blood eosinophil counts were significantly affected by the nutritional history in lambs but not in kids. The lowest FEC was found for lambs placed in high dietary conditions, however during the same period body weight loss was observed in this group. In low dietary conditions, kids were more resistant than lambs and the ADG was higher in lambs. However, the anaemia and the level of serum pepsinogen, marker of the abomasal mucosa integrity, were higher in kids. Our data suggest that the impact of the post-weaning nutritional history on the response to an experimental H. contortus infection is significantly affected by the host species. PMID- 26872935 TI - Efficacy and persistent activity of moxidectin against natural Muellerius capillaris infection in goats and pathological consequences of muelleriosis. AB - The effect of moxidectin against natural Muellerius capillaris infection in goats was evaluated in this study. Long-acting moxidectin at a single dose of 1 mg kg( 1) body weight was administered to an entire flock (n=10) of goats. The individual faecal larval count reduction was applied as an indicator of treatment efficacy. A significant reduction (>98%) in larval counts was observed in all surveyed animals 14 days after drug administration. Moxidectin demonstrated persistent activity in this study; the mean faecal larval count reduction was 99.1% +/- 1.8 on day 77 of the treatment. Macroscopic abnormalities and histological changes in the lungs of two infected goats were evident during the post-mortem examination. The pathological consequences of M. capillaris infection were observed even three months after parasite elimination. The results of this study indicate that moxidectin is a highly effective anthelmintic agent for the control of muelleriosis in goats. This drug provides animals with fifteen weeks of protections against M. capillaris reinfection. PMID- 26872936 TI - FAMACHA((c)) scores history of sheep characterized as resistant/resilient or susceptible to H. contortus in artificial infection challenge. AB - With the aim of validating the FAMACHA((c)) as a method for phenotypic selection of sheep resistant/resilient to gastrointestinal nematodes, 27 Suffolk ewes with known FAMACHA((c)) score histories were experimentally infected with 25,000 larvae of Haemonchus contortus. From the day of infection (day 0) to 60 days post infection, at intervals of 7-15 days, ewes were evaluated for packed cell volume (PCV) and fecal egg counts (FEC). A statistically significant increase (p<0.05) in FEC occurred between day 0 and day 60. PCV values showed a decrease (p<0.05) starting from day 21, compared to day 0. Based on the changes in FEC and PCV values from day 0 to day 60, 15 ewes (55.56%) were classified as susceptible (S) and 12 ewes (44.44%) as resistant/resilient (RR). A comparison of the average FEC after infection between susceptible (4487.6 eggs per gram-epg) and resistant/resilient (1317.9epg) ewes showed a significant difference (p<0.05) between the two groups. The difference in average PCV values after infection (24.8% and 30.3% for S and RR, respectively) was also significant (p<0.05). Data from 980 previous evaluations of FAMACHA((c)) scores from the 27 ewes showed that 58.33% of the ewes classified as RR and 46.67% of the S group had a history of only F1 and F2 scores. In the RR group, only one animal (8.33%) had an F4 score, occurring one time out of the 61 evaluations of this ewe. In contrast, 40.0% of S group ewes had F4 and/or F5 scores. During the period of FAMACHA((c)) score history that was evaluated, 69.56% of the total number of anthelmintic treatments in the flock were administered to ewes from group S. Since ewes with F4 and/or F5 scores during the FAMACHA((c)) score time period were classified as susceptible during the experimental infection (with the exception of one ewe), we conclude that the FAMACHA((c)) score history is a useful tool for the selection of ewes that are resistant/resilient, as well as for the identification of susceptible animals that should be culled. PMID- 26872937 TI - Flap Dynamics in Aspartic Proteases: A Computational Perspective. AB - Recent advances in biochemistry and drug design have placed proteases as one of the critical target groups for developing novel small-molecule inhibitors. Among all proteases, aspartic proteases have gained significant attention due to their role in HIV/AIDS, malaria, Alzheimer's disease, etc. The binding cleft is covered by one or two beta-hairpins (flaps) which need to be opened before a ligand can bind. After binding, the flaps close to retain the ligand in the active site. Development of computational tools has improved our understanding of flap dynamics and its role in ligand recognition. In the past decade, several computational approaches, for example molecular dynamics (MD) simulations, coarse grained simulations, replica-exchange molecular dynamics (REMD) and metadynamics, have been used to understand flap dynamics and conformational motions associated with flap movements. This review is intended to summarize the computational progress towards understanding the flap dynamics of proteases and to be a reference for future studies in this field. PMID- 26872938 TI - Small fiber neuropathy: Getting bigger! AB - Etiological and clinical heterogeneity of small fiber neuropathy (SFN) precludes a unifying approach and necessitates reliance on recognizable clinical syndromes. Symptoms of SFN arise from dysfunction in nociception, temperature, and autonomic modalities. This review focuses on SFN involving nociception and temperature, examining epidemiology, etiology, clinical presentation, diagnosis, pathophysiology, and management. Prevalence of SFN is 52.95 per 100,000 population, and diabetes and idiopathic are the most common etiologies. Dysesthesia, allodynia, pain, burning, and coldness sensations frequently present in a length-dependent pattern. Additional autonomic features in gastrointestinal, urinary, or cardiovascular systems are frequent but poorly objectified. SFN is diagnosed by intraepidermal nerve fiber density and quantitative sensory and autonomic tests in combination with normal nerve conduction. Pathophysiological understanding centers on sodium channel dysfunction, and genetic forms are beginning to be understood. Treatment is directed at the underlying etiology supported by symptomatic treatment using antidepressants and anticonvulsants. Little is known about long-term outcomes, and systematic cohort studies are needed. PMID- 26872940 TI - Design Considerations for Smoking Cessation Apps: Feedback From Nicotine Dependence Treatment Providers and Smokers. AB - BACKGROUND: Hundreds of smoking cessation apps are commercially available, but most are not theory-based or designed to take advantage of mobile technology in ways that could make them more engaging and possibly more effective. Considering input from both clinical experts (who understand best practice nicotine dependence treatment requirements) to inform appropriate content and from smokers (the end users) to express their preferences is important in designing these programs in the future. OBJECTIVE: To assess and compare the opinions of nicotine dependence treatment providers and smokers regarding the design of future smoking cessation apps. METHODS: We surveyed providers (n=264) and smokers who own smartphones (n=40) to assess their opinions on the importance of 21 app design features. Features represented 5 domains: cost, reputation, privacy and security, content and user experience, and communication. Domains were chosen to reflect best practice treatment, leverage mobile technology to support smoking cessation, and elicit important user preferences. Data were collected between June and July 2015. RESULTS: Most providers agreed that mHealth apps hold promise for helping people quit smoking (203/264, 76.9%) and would recommend them to their clients/patients (201/264, 76.1%), especially if the app were empirically validated (236/264, 89.4%). Few providers believe effective cessation apps currently exist (112/264, 42.4%). Few smokers (5/40, 13%) had ever downloaded a smoking cessation app; of the ones who had not, most said they would consider doing so (29/35, 83%). Both respondent groups indicated the following features were very to extremely important to include in cessation apps: free or low cost, keeps information private, matches individual needs and interests, adapts as one's needs and interests change, helps to manage nicotine withdrawal symptoms and medication side effects, and allows users to track their progress. Providers and smokers also indicated gaming and social media connectivity were less important than other features. Despite these similarities, the groups had significantly different opinions about the relative importance of various features. In particular, providers rated privacy as the most important feature, whereas smokers rated low cost and the ability to adaptively tailor content as the most important features. CONCLUSIONS: Smoking cessation apps hold great promise as intervention tools but only if they engage users and appropriately treat nicotine dependence. Intervention development should take into consideration the perspectives of both treatment experts and smokers. This paper highlights important perspectives from each of these groups to be considered when designing future app-based smoking cessation programs. PMID- 26872941 TI - Diagnosing Developmental Dysplasia of Hip in Newborns Using Clinical Screen and Ultrasound of Hips-An Indian Experience. AB - AIM: To study the cost-effectiveness of clinical screen with ultrasonography (USG) of hip for diagnosing developmental dysplasia of the hip (DDH) in newborns. METHODS: Retrospective study (2006-14). Term newborns had (i) target scan at 6 weeks-family history of DDH or breech presentation-and (ii) early scan-abnormal clinical screen. RESULTS: In all, 736 babies had USG scan. Five early scans (Graf's classification; three Type IIA, one Type IIC and one Type IIIB] and 15 target scans (Type IIA) were reported abnormal. All Type IIA DDH had subsequent 12 weeks' scans normal. Babies with Type IIIB and IIC had hip reduction surgery at 6 and 16 months of age, respectively. At cost 200 INR/scan, total 147 200 INR was incurred against two possible hip replacements prevented. CONCLUSION: Universal clinical screen with USG of hip can aid in early diagnosis of DDH in newborns. Large population-based studies from developing countries need to look in its cost-effectiveness. PMID- 26872939 TI - Evaluation of genetic variation among Brazilian soybean cultivars through genome resequencing. AB - BACKGROUND: Soybean [Glycine max (L.) Merrill] is one of the most important legumes cultivated worldwide, and Brazil is one of the main producers of this crop. Since the sequencing of its reference genome, interest in structural and allelic variations of cultivated and wild soybean germplasm has grown. To investigate the genetics of the Brazilian soybean germplasm, we selected soybean cultivars based on the year of commercialization, geographical region and maturity group and resequenced their genomes. RESULTS: We resequenced the genomes of 28 Brazilian soybean cultivars with an average genome coverage of 14.8X. A total of 5,835,185 single nucleotide polymorphisms (SNPs) and 1,329,844 InDels were identified across the 20 soybean chromosomes, with 541,762 SNPs, 98,922 InDels and 1,093 CNVs that were exclusive to the 28 Brazilian cultivars. In addition, 668 allelic variations of 327 genes were shared among all of the Brazilian cultivars, including genes related to DNA-dependent transcription elongation, photosynthesis, ATP synthesis-coupled electron transport, cellular respiration, and precursors of metabolite generation and energy. A very homogeneous structure was also observed for the Brazilian soybean germplasm, and we observed 41 regions putatively influenced by positive selection. Finally, we detected 3,880 regions with copy-number variations (CNVs) that could help to explain the divergence among the accessions evaluated. CONCLUSIONS: The large number of allelic and structural variations identified in this study can be used in marker-assisted selection programs to detect unique SNPs for cultivar fingerprinting. The results presented here suggest that despite the diversification of modern Brazilian cultivars, the soybean germplasm remains very narrow because of the large number of genome regions that exhibit low diversity. These results emphasize the need to introduce new alleles to increase the genetic diversity of the Brazilian germplasm. PMID- 26872942 TI - Excitotoxic Mechanisms in Non-Motor Dysfunctions and Levodopa- Induced Dyskinesia in Parkinson's Disease: The Role of the Interaction Between the Dopaminergic and the Kynurenine System. AB - Parkinson's disease is a common progressive neurodegenerative disorder presenting with characteristic motor symptoms. Non-motor dysfunctions and therapyrelated complications frequently develop, but are often underdiagnosed and undertreated. Levodopa- induced dyskinesia and impulse control disorders are suggested to share pathophysiological processes and m a y be related to alterations of the glutamatergic neurotransmission. Anti- glutamatergic interventions are therefore worth considering: several lines of evidence already indicate their beneficial effect. The kynurenine pathway offers the endogenous glutamate receptor antagonist kynurenic acid, which may act as a promising candidate for future drug development with the aim of assessment of the motor symptoms and therapy-related complications of Parkinson's disease. PMID- 26872945 TI - Should pre-implantation genetic screening be implemented to routine clinical practice? AB - The utilization of trophectoderm biopsy combined with comprehensive chromosome screening (CCS) tests for embryonic aneuploidy was recently suggested to improve IVF outcome, however, not without criticisms. Since mosaicism has been reported in as high as 90% of blastocyst-stage embryos, we aimed to evaluate the accuracy of trophectoderm multiple biopsies using next-generation sequencing (NGS). Eight top quality blastocysts underwent three trophectoderm biopsies each, followed by NGS. In four blastocysts, the rest of the embryo, which included the inner cell mass, was also analyzed. Five of the 24 (20.8%) trophectoderm biopsies revealed inconclusive results, while 4 (16.6%) demonstrated embryonic mosaicism. Overall, 10 (35.7%) of the 28 (24 trophectoderms and 4 inner cell masses) biopsies revealed mosaicism or inconclusive results. Our preliminary observations contribute to the ongoing discussion on the unrestricted clinical adoption of PGS, suggesting, that until proper evaluation of its effectiveness and cost effectiveness will be provided, PGS should be offered only under study conditions, and with appropriate informed consents. PMID- 26872944 TI - Are temporal patterns of sitting associated with obesity among blue-collar workers? A cross sectional study using accelerometers. AB - BACKGROUND: Little is known about associations of temporal patterns of sitting (i.e., distribution of sitting across time) with obesity. We aimed investigating the association between temporal patterns of sitting (long, moderate and brief uninterrupted bouts) and obesity indicators (body mass index (BMI), waist circumference and fat percentage), independently from moderate-vigorous physical activity (MVPA) and total sitting time among blue-collar workers. METHODS: Workers (n = 205) wore Actigraph GT3X+ accelerometers on the thigh and trunk for 1-4 working days. Using the validated Acti4 software, the total sitting time and time spent sitting in brief (<=5 mins), moderate (>5 and <=30 mins), and long (>30mins) bouts on working days were determined for the whole day, and for leisure and work separately. BMI (kg/m(2)), waist circumference (cm) and fat percentage were objectively measured. RESULTS: Results of linear regression analysis adjusted for multiple confounders indicated that brief bouts of sitting was negatively associated with obesity for the whole day (BMI, P < 0.01; fat percentage, P < 0.01; waist circumference, P < 0.01) and work (BMI, P < 0.01; fat percentage, P < 0.01; waist circumference, P < 0.01), but not for leisure. Sitting time in long bouts was positively associated with obesity indicators for the whole day (waist circumference, P = 0.05) and work (waist circumference, P = 0.01; BMI, P = 0.04), but not leisure. CONCLUSIONS: For the whole day as well as for work, brief bouts and long bouts of sitting showed opposite associations with obesity even after adjusting for MVPA and total sitting time, while sitting during leisure did not show these associations. Thus, the temporal distribution of sitting seems to influence the relationship between sitting and obesity. PMID- 26872946 TI - Tactical emergency medicine: lessons from Paris marauding terrorist attack. PMID- 26872943 TI - Expression of Arabidopsis Bax Inhibitor-1 in transgenic sugarcane confers drought tolerance. AB - The sustainability of global crop production is critically dependent on improving tolerance of crop plants to various types of environmental stress. Thus, identification of genes that confer stress tolerance in crops has become a top priority especially in view of expected changes in global climatic patterns. Drought stress is one of the abiotic stresses that can result in dramatic loss of crop productivity. In this work, we show that transgenic expression of a highly conserved cell death suppressor, Bax Inhibitor-1 from Arabidopsis thaliana (AtBI 1), can confer increased tolerance of sugarcane plants to long-term (>20 days) water stress conditions. This robust trait is correlated with an increased tolerance of the transgenic sugarcane plants, especially in the roots, to induction of endoplasmic reticulum (ER) stress by the protein glycosylation inhibitor tunicamycin. Our findings suggest that suppression of ER stress in C4 grasses, which include important crops such as sorghum and maize, can be an effective means of conferring improved tolerance to long-term water deficit. This result could potentially lead to improved resilience and yield of major crops in the world. PMID- 26872947 TI - Referrals for pulmonary hypertension rise by 21% in five years, audit finds. PMID- 26872949 TI - Herbivore-Triggered Electrophysiological Reactions: Candidates for Systemic Signals in Higher Plants and the Challenge of Their Identification. AB - In stressed plants, electrophysiological reactions (elRs) are presumed to contribute to long-distance intercellular communication between distant plant parts. Because of the focus on abiotic stress-induced elRs in recent decades, biotic stress-triggered elRs have been widely ignored. It is likely that the challenge to identify the particular elR types (action potential [AP], variation potential, and system potential [SP]) was responsible for this course of action. Thus, this survey focused on insect larva feeding (Spodoptera littoralis and Manduca sexta) that triggers distant APs, variation potentials, and SPs in monocotyledonous and dicotyledonous plant species (Hordeum vulgare, Vicia faba, and Nicotiana tabacum). APs were detected only after feeding on the stem/culm, whereas SPs were observed systemically following damage to both stem/culm and leaves. This was attributed to the unequal vascular innervation of the plant and a selective electrophysiological connectivity of the plant tissue. However, striking variations in voltage patterns were detected for each elR type. Further analyses (also in Brassica napus and Cucurbita maxima) employing complementary electrophysiological approaches in response to different stimuli revealed various reasons for these voltage pattern variations: an intrinsic plasticity of elRs, a plant-specific signature of elRs, a specific influence of the applied (a)biotic trigger, the impact of the technical approach, and/or the experimental setup. As a consequence, voltage pattern variations, which are not irregular but rather common, need to be included in electrophysiological signaling analysis. Due to their widespread occurrence, systemic propagation, and respective triggers, elRs should be considered as candidates for long-distance communication in higher plants. PMID- 26872948 TI - The Mechanistic Underpinnings of an ago1-Mediated, Environmentally Dependent, and Stochastic Phenotype. AB - The crucial role of microRNAs in plant development is exceedingly well supported; their importance in environmental robustness is studied in less detail. Here, we describe a novel, environmentally dependent phenotype in hypomorphic argonaute1 (ago1) mutants and uncover its mechanistic underpinnings in Arabidopsis (Arabidopsis thaliana). AGO1 is a key player in microRNA-mediated gene regulation. We observed transparent lesions on embryonic leaves of ago1 mutant seedlings. These lesions increased in frequency in full-spectrum light. Notably, the lesion phenotype was most environmentally responsive in ago1-27 mutants. This allele is thought to primarily affect translational repression, which has been linked with the response to environmental perturbation. Using several lines of evidence, we found that these lesions represent dead and dying tissues due to an aberrant hypersensitive response. Although all three canonical defense hormone pathways (salicylic acid, jasmonate, and jasmonate/ethylene pathways) were up regulated in ago1 mutants, we demonstrate that jasmonate perception drives the lesion phenotype. Double mutants of ago1 and coronatine insensitive1, the jasmonate receptor, showed greatly decreased frequency of affected seedlings. The chaperone HEAT SHOCK PROTEIN 90 (HSP90), which maintains phenotypic robustness in the face of environmental perturbations, is known to facilitate AGO1 function. HSP90 perturbation has been shown previously to up-regulate jasmonate signaling and to increase plant resistance to herbivory. Although single HSP90 mutants showed subtly elevated levels of lesions, double mutant analysis disagreed with a simple epistatic model for HSP90 and AGO1 interaction; rather, both appeared to act nonadditively in producing lesions. In summary, our study identifies AGO1 as a major, largely HSP90-independent, factor in providing environmental robustness to plants. PMID- 26872950 TI - Impact of serum as a dispersion agent for in vitro and in vivo toxicological assessments of TiO2 nanoparticles. AB - Nanoparticles (NP) have a tendency to agglomerate after dispersion in physiological media, which can be prevented by the addition of serum. This may however result in modification of the toxic potential of particles due to the formation of protein corona. Our study aimed to analyze the role of serum that is added to improve the dispersion of 10 nm TiO2 NPs on in vitro and in vivo effects following the exposure via the respiratory route. We characterized NP size, surface charge, sedimentation rate, the presence of protein corona and the oxidant-generating capacity after NP dispersion in the presence/absence of serum. The effect of serum on NP internalization, cytotoxicity and pro-inflammatory responses was assessed in a human pulmonary cell line, NCI-H292. Serum in the dispersion medium led to a slower sedimentation, but an enhanced cellular uptake of TiO2 NPs. Despite this greater uptake, the pro-inflammatory response in NCI H292 cells was lower after serum supplementation (used either as a dispersant or as a cell culture additive), which may be due to a reduced intrinsic oxidative potential of TiO2 NPs. Interestingly, serum could be added 2 h after the NP treatment without affecting the pro-inflammatory response. We also determined the acute pulmonary and hepatic toxicity in vivo 24 h after intratracheal instillation of TiO2 NPs in C57BL/6N mice. The use of serum resulted in an underestimation of the local acute inflammatory response in the lung, while a systemic response on glutathione reduction remained unaffected. In conclusion, serum as a dispersion agent for TiO2 NPs can lead to an underestimation of the acute pro-inflammatory response in vitro and in vivo. To avoid potential unwanted effects of dispersants and medium components, we recommend that the protocol of NM preparation should be thoroughly tested, and reflect as close as possible realistic exposure conditions. PMID- 26872951 TI - Comparative analysis of 3D culture methods on human HepG2 cells. AB - Human primary hepatocytes represent a gold standard in in vitro liver research. Due to their low availability and high costs alternative liver cell models with comparable morphological and biochemical characteristics have come into focus. The human hepatocarcinoma cell line HepG2 is often used as a liver model for toxicity studies. However, under two-dimensional (2D) cultivation conditions the expression of xenobiotic-metabolizing enzymes and typical liver markers such as albumin is very low. Cultivation for 21 days in a three-dimensional (3D) Matrigel culture system has been reported to strongly increase the metabolic competence of HepG2 cells. In our present study we further compared HepG2 cell cultivation in three different 3D systems: collagen, Matrigel and Alvetex culture. Cell morphology, albumin secretion, cytochrome P450 monooxygenase enzyme activities, as well as gene expression of xenobiotic-metabolizing and liver-specific enzymes were analyzed after 3, 7, 14, and 21 days of cultivation. Our results show that the previously reported increase of metabolic competence of HepG2 cells is not primarily the result of 3D culture but a consequence of the duration of cultivation. HepG2 cells grown for 21 days in 2D monolayer exhibit comparable biochemical characteristics, CYP activities and gene expression patterns as all 3D culture systems used in our study. However, CYP activities did not reach the level of HepaRG cells. In conclusion, the increase of metabolic competence of the hepatocarcinoma cell line HepG2 is not due to 3D cultivation but rather a result of prolonged cultivation time. PMID- 26872952 TI - An anatomical study of the pterygospinous bar and foramen of Civinini. AB - PURPOSE: The pterygospinous ligament extends from the posterior free margin of the lateral pterygoid plate till the spine of the sphenoid. The ligament may ossify partly or completely leading to the formation of the pterygospinous bar. A complete ossification of the ligament results in the formation of the foramen of Civinini. Presence of the complete or incomplete pterygospinous bar may lead to a difficulty in passing the needle during anaesthesia for the trigeminal neuralgia or the bar may also compress the mandibular nerve and its branches to cause lingual numbness, pain and speech impairment. METHOD: Presence of the complete or incomplete pterygospinous bar and the foramen of Civinini were studied in 55 dried adult skulls and 20 sphenoid bones. RESULTS: Partial or complete ossification of the pterygospinous ligament was seen in 17.33 % skulls. One skull showed the presence of bilateral complete pterygospinous bar while another skull had the unilateral complete pterygospinous bar on right side. Two skulls and one sphenoid had bilateral incomplete pterygospinous bar while seven skulls and one sphenoid bone had unilateral incomplete pterygospinous bar. In three cases, the bar was passing just below the foramen ovale. CONCLUSION: The pterygospinous bar when present medial to the foramen ovale may not have much clinical significance but when the bar is present just below the foramen ovale, it may cause a compression of the mandibular nerve and its branches and may also obstruct the passage for the transoval approach to the neighbouring regions. PMID- 26872953 TI - Ultraviolet B Phototherapy for Psoriasis: Review of Practical Guidelines. AB - Psoriasis is an inflammatory skin condition that affects approximately 2 % of people worldwide. Topical treatments, systemic treatments, biologic agents, and phototherapy are all treatment options for psoriasis. Ultraviolet (UV) B phototherapy is most appropriate for patients with >10 % affected body surface area who have not responded to topical treatments. This review outlines the use, dosage, safety, and efficacy of narrowband UVB (NB-UVB) and targeted phototherapy. NB-UVB and excimer laser are effective treatment options for psoriasis; they are administered two to three times weekly until clearance followed by maintenance treatment before discontinuation. Long-term data on NB UVB indicate that it has a good safety profile. NB-UVB is commonly used with adjunctive topical treatments such as emollients, calcipotriene, cortico steroids, retinoids, and tar. NB-UVB can be used in selected patients with traditional systemic agents such as methotrexate, mycophenolate mofetil, and cyclosporine, although the duration of the combined treatment should be kept to a minimum and patients need to be closely monitored. Acitretin can be safely used with phototherapy, but robust data on the combination use of biologic agents or phosphodiesterase inhibitors with phototherapy are lacking. PMID- 26872954 TI - Cutaneous Lupus Erythematosus: An Update on Pathogenesis, Diagnosis and Treatment. AB - Cutaneous lupus erythematosus (CLE) includes a broad range of dermatologic manifestations, which may or may not be associated with systemic disease. Recent studies in this area continue to shape our understanding of this disease and treatment options. Epidemiologic studies have found an incidence of CLE of 4.30 per 100,000, which approaches similar analysis for systemic lupus erythematosus (SLE). Although there have been extensive efforts to define SLE, the classification of CLE and its subgroups remains a challenge. Currently, diagnosis relies on clinical and laboratory findings as well as skin histology. The Cutaneous Lupus Area and Severity IndexTM (CLASITM) is a validated measure of disease activity and damage. CLE pathogenesis is multifactorial and includes genetic contributions as well as effects of ultraviolet (UV) light. Immune dysregulation and aberrant cell signaling pathways through cytokine cascades are also implicated. Patient education and avoidance of triggers are key to disease prevention. Antimalarials and topical steroids continue to be the standard of care; however, immunosuppressants, thalidomide analogs and monoclonal antibodies are possible systemic therapies for the treatment of recalcitrant disease. PMID- 26872955 TI - Social Skills Training for Adolescents With Intellectual Disabilities: A School Based Evaluation. AB - Individuals with intellectual disabilities (ID) often demonstrate impairments in social functioning, with deficits becoming more apparent during adolescence. This study evaluated the effects of the Superheroes Social Skills program, a program that combines behavioral skills training and video modeling to teach target social skills, on accurate demonstration of three target social skills in adolescents with ID. Skills taught in the present study include Expressing Wants and Needs, Conversation, and Turn Taking. Four adolescents with ID participated in a 3-week social skills intervention, with the intervention occurring twice per week. A multiple baseline across skills design was used to determine the effect of the intervention on social skill accuracy in both a training and generalization setting. All participants demonstrated substantial improvements in skill accuracy in both settings, with teacher ratings of social functioning further suggesting generalization of social skills to nontraining settings. PMID- 26872956 TI - Noncontingent Reinforcement to Improve Classroom Behavior of a Student With Developmental Disability. AB - The purpose of this study was to examine the effects of a noncontingent reinforcement intervention package implemented by an interning teacher in a special education classroom to address disruptive behavior and task engagement for a third-grade, 8-year-old boy with developmental disability. Using a within subject reversal design (A-B-A-B), a teacher interning in Max's classroom delivered 3-min breaks (i.e., escape) from classroom tasks on a fixed-time 2-min interval schedule for five daily sessions during the first intervention phase and for five daily sessions during the reimplementation phase; breaks were not contingent on his behavior. The intervention package also included a reinforcement menu for the student to select daily from escape activities (i.e., preferred activities including swinging and taking a walk) and a picture prompt to provide a continuous, visual reminder of the upcoming reinforcer. Results indicated increases in task engagement and decreases in disruptive behavior during phases when the intervention was applied. Implications for future research and practice are discussed. PMID- 26872958 TI - The Effects of a Brief Acceptance-Based Behavioral Treatment Versus Traditional Cognitive-Behavioral Treatment for Public Speaking Anxiety: An Exploratory Trial Examining Differential Effects on Performance and Neurophysiology. AB - Individuals with public speaking anxiety (PSA) experience fear and avoidance that can cause extreme distress, impaired speaking performance, and associated problems in psychosocial functioning. Most extant interventions for PSA emphasize anxiety reduction rather than enhancing behavioral performance. We compared the efficacy of two brief cognitive-behavioral interventions, a traditional cognitive behavior treatment (tCBT) and an acceptance-based behavior treatment (ABBT), on public speaking performance and anxiety in a clinical sample of persons with PSA. The effects of treatment on prefrontal brain activation were also examined. Participants (n = 21) were randomized to 90 min of an ABBT or a tCBT intervention. Assessments took place at pre- and post-treatment and included self rated anxiety and observer-rated performance measures, a behavioral assessment, and prefrontal cortical activity measurements using functional near-infrared spectroscopy (fNIRS). Exploratory results indicated that participants in the ABBT condition experienced greater improvements in observer-rated performance relative to those in the tCBT condition, while those in the tCBT condition experienced greater reductions in subjective anxiety levels. Individuals in the ABBT condition also exhibited a trend toward greater treatment-related reductions in blood volume in the left dorsolateral prefrontal cortex relative to those who received tCBT. Overall, these findings preliminarily suggest that acceptance based treatments may free more cognitive resources in comparison with tCBT, possibly resulting in greater improvements in objectively rated behavioral performances for ABBT interventions. PMID- 26872957 TI - Examining Effectiveness of Group Cognitive-Behavioral Therapy for Externalizing and Internalizing Disorders in Urban Schools. AB - This article presents outcome data of the implementation of three group cognitive behavioral therapy (GCBT) interventions for children with externalizing behavior problems, anxiety, and depression. School counselors and graduate students co-led the groups in two low-income urban schools. Data were analyzed to assess pre treatment to post-treatment changes in diagnostic severity level. Results of the exploratory study indicated that all three GCBT protocols were effective at reducing diagnostic severity level for children who had a primary diagnosis of an externalizing disorder, anxiety disorder, or depressive disorder at the clinical or intermediate (at-risk) level. All three GCBT protocols were implemented with relatively high levels of fidelity. Data on the effectiveness of the interventions for reducing diagnostic severity level for externalizing and internalizing spectrum disorders and for specific disorders are presented. A discussion of implementation of mental health evidence-based interventions in urban schools is provided. PMID- 26872960 TI - Minimalistic toy robot to analyze a scenery of speaker-listener condition in autism. AB - Atypical neural architecture causes impairment in communication capabilities and reduces the ability of representing the referential statements of other people in children with autism. During a scenery of "speaker-listener" communication, we have analyzed verbal and emotional expressions in neurotypical children (n = 20) and in children with autism (n = 20). The speaker was always a child, and the listener was a human or a minimalistic robot which reacts to speech expression by nodding only. Although both groups performed the task, everything happens as if the robot could allow children with autism to elaborate a multivariate equation encoding and conceptualizing within his/her brain, and externalizing into unconscious emotion (heart rate) and conscious verbal speech (words). Such a behavior would indicate that minimalistic artificial environments such as toy robots could be considered as the root of neuronal organization and reorganization with the potential to improve brain activity. PMID- 26872961 TI - Stage IV sporadic Burkitt's leukaemia with osteolysis in the maxillary sinuses. AB - We present a case of paediatric Stage IV sporadic Burkitt's leukaemia presenting as cheek enlargement with osteolysis of the maxilla. An 8-year-old boy was referred to our department with diffuse swelling of both cheeks. Head and neck examination revealed bilateral diffuse nontender swelling, non-fluctuant but slightly compressible. Computed tomography imaging showed enhancing bilateral bulky lesions expanding the maxillary sinuses, with associated osteolysis in the posterior walls of both sinuses. Laboratory results included blast cells in the peripheral blood, suggesting a haematopoietic tumour. We referred the patient to the Department of Paediatric Haematology and Oncology. Additional examinations eventually led to the diagnosis of Stage IV sporadic Burkitt's leukaemia. PMID- 26872962 TI - Characterizing Dust from Cutting Corian(r), a Solid-Surface Composite Material, in a Laboratory Testing System. AB - We conducted a laboratory test to characterize dust from cutting Corian((r)), a solid-surface composite material, with a circular saw. Air samples were collected using filters and direct-reading instruments in an automatic laboratory testing system. The average mass concentrations of the total and respirable dusts from the filter samples were 4.78+/-0.01 and 1.52+/-0.01mg cm(-3), respectively, suggesting about 31.8% mass of the airborne dust from cutting Corian((r)) is respirable. Analysis of the metal elements on the filter samples reveals that aluminum hydroxide is likely the dominant component of the airborne dust from cutting Corian((r)), with the total airborne and respirable dusts containing 86.0+/-6.6 and 82.2+/-4.1% aluminum hydroxide, respectively. The results from the direct-reading instruments confirm that the airborne dust generated from cutting Corian((r)) were mainly from the cutting process with very few particles released from the running circular saw alone. The number-based size distribution of the dusts from cutting Corian((r)) had a peak for fine particles at 1.05 um with an average total concentration of 871.9 particles cm(-3), and another peak for ultrafine particles at 11.8nm with an average total concentration of 1.19*10(6) particles cm(-3) The small size and high concentration of the ultrafine particles suggest additional investigation is needed to study their chemical composition and possible contribution to pulmonary effect. PMID- 26872959 TI - An enriched environment and 17-beta estradiol produce similar pro-cognitive effects on ovariectomized rats. AB - Estrogen depletion due to aging, surgery or pathological events can cause a multitude of problems, including neurodegenerative alterations. In rodents without ovaries, 17-beta estradiol (E2) has been shown to produce beneficial effects on cognition, stimulating brain regions (e.g., the neocortex, hippocampus and amygdala) related to cognition and learning. Another treatment that stimulates these brain regions is an enriched environment (EE), which is a complex set of external factors in the immediate surroundings that facilitates greater stimulation of sensorial, cognitive and motor circuits of the brain. The aim of the present study was to test, using an animal model of ovariectomy induced impairment of memory, the relative effect of E2 (with a time-released pellet; 1 MUg/rat/day), EE exposure and a combination of both treatments. Experimental and control groups were submitted to two memory tests 18 weeks post surgery: the autoshaping learning task (ALT) for measuring associative learning and the novel object recognition test (NORT) for evaluating short- and long-term memory. To assess potential motor impairments caused by treatments, all rats were tested after the ALT in an automatic activity counter. Results from ALT show that the ovariectomy blocked the conditioned responses displayed, an effect rescued by chronic treatment with estrogen or EE exposure. The combination of both treatments did not improve the results obtained separately. In the NORT, the exploration time for recognizing a novel object was similar in the short run with all groups, but greater in the long run with hormone administration or EE exposure. As with the ALT, in the NORT there was no improvement shown by the combination treatment. These data were not masked by changes in spontaneous activity because this parameter was not modified in the rats by either treatment. Possible action mechanisms are proposed, taking into account the role of corticosterone and BDNF on cognition. PMID- 26872963 TI - Impact of SERVE-HF on management of sleep disordered breathing in heart failure: a call for further studies. AB - Sleep disordered breathing (SDB) (obstructive sleep apnea, central sleep apnea/Cheyne-Stokes respiration or the combination of both) is highly prevalent in patients with a wide variety of cardiovascular diseases including hypertension, arrhythmia, coronary artery disease, myocardial infarction and stroke (reviewed previously in the September issue of this journal). Its close association with outcomes in chronic heart failure with reduced ejection fraction (HF-REF) suggests that it may be a potential treatment target. Herein, we provide an update on SDB and its treatment in HF-REF. PMID- 26872964 TI - Mutation Update and Review of Severe Methylenetetrahydrofolate Reductase Deficiency. AB - Severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency is caused by mutations in the MTHFR gene and results in hyperhomocysteinemia and varying severity of disease, ranging from neonatal lethal to adult onset. Including those described here, 109 MTHFR mutations have been reported in 171 families, consisting of 70 missense mutations, 17 that primarily affect splicing, 11 nonsense mutations, seven small deletions, two no-stop mutations, one small duplication, and one large duplication. Only 36% of mutations recur in unrelated families, indicating that most are "private." The most common mutation is c.1530A>G (numbered from NM_005957.4, p.Lys510 = ) causing a splicing defect, found in 13 families; the most common missense mutation is c.1129C>T (p.Arg377Cys) identified in 10 families. To increase disease understanding, we report enzymatic activity, detected mutations, and clinical onset information (early, <1 year; or late, >1 year) for all published patients available, demonstrating that patients with early onset have less residual enzyme activity than those presenting later. We also review animal models, diagnostic approaches, clinical presentations, and treatment options. This is the first large review of mutations in MTHFR, highlighting the wide spectrum of disease-causing mutations. PMID- 26872966 TI - A case of mutism on emergence from general anesthesia. PMID- 26872965 TI - Protective Role of Religious Involvement Against Depression and Suicidal Ideation Among Youth with Interpersonal Problems. AB - This study examined religious involvement-private religious practices (PRP), organizational religiousness (OR), and religious support (RS)-in relation to depressive symptoms and suicidal ideation (SI) and its protective role, considering youths' school and parent-family connectedness. Youth, ages 12-15 (n = 161), were screened for peer victimization, bullying perpetration, and low social connectedness, and assessed for depressive symptoms, SI, school connectedness, parent-family connectedness, and religious involvement. Results indicated PRP and RS were associated with lower levels of depressive symptoms; PRP and OR were associated with less SI. Controlling for connectedness, PRP remained associated with less SI only. Results suggest the importance of considering religious involvement as a target of youth depression and suicide prevention interventions. PMID- 26872967 TI - Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease. AB - PURPOSE: To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD). DESIGN: Case series. PARTICIPANTS: A total of 562 patients diagnosed with IRD. METHODS: We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data. MAIN OUTCOME MEASURES: Diagnostic yield of genomic testing. RESULTS: Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15-45) uplift in diagnostic yield. CONCLUSIONS: We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS. PMID- 26872968 TI - Multidisciplinary approach to breast angiosarcoma in an elderly patient: Repeated local relapses and significant objective responses. AB - Angiosarcomas are malignant tumors of endovascular origin, which may be divided into primary and secondary forms. Secondary breast angiosarcomas are an increasing problem, especially in patients treated with breast-conserving surgery followed by radiotherapy.We report a case of radiation-induced angiosarcoma of the breast in a 77-year-old woman who presented with a suspect lesion in her left breast. Excisional biopsy and subsequent immunohistochemical staining of the specimen was performed. Histological report was diagnostic for low-intermediate grade angiosarcoma. The tumor cells were diffusely positive for CD31 and CD34. We performed surgical resection with mastectomy.A multidisciplinary approach with bleomycin-based electrochemotherapy, radiation treatment, and chemotherapy with pegylated liposomal doxorubicin has been most useful to control subsequent local relapses. To date, the patient is under close observation and is performing well. No recurrence has been demonstrated after ending of chemotherapy. PMID- 26872969 TI - How RNase R Degrades Structured RNA: ROLE OF THE HELICASE ACTIVITY AND THE S1 DOMAIN. AB - RNase R, a ubiquitous 3' exoribonuclease, plays an important role in many aspects of RNA metabolism. In contrast to other exoribonucleases, RNase R can efficiently degrade highly structured RNAs, but the mechanism by which this is accomplished has remained elusive. It is known that RNase R contains an unusual, intrinsic RNA helicase activity that facilitates degradation of duplex RNA, but how it stimulates the nuclease activity has also been unclear. Here, we have made use of specifically designed substrates to compare the nuclease and helicase activities of RNase R. We have also identified and mutated several residues in the S1 RNA binding domain that are important for interacting with duplex RNA and have measured intrinsic tryptophan fluorescence to analyze the conformational changes that occur upon binding of structured RNA. Using these approaches, we have determined the relation of the RNA helicase, ATP binding, and nuclease activities of RNase R. This information has been combined with a structural analysis of RNase R, based on its homology to RNase II, whose structure has been determined, to develop a detailed model that explains how RNase R digests structured RNA and how this differs from its action on single-stranded RNA. PMID- 26872970 TI - A Conserved Pocket in the Dengue Virus Polymerase Identified through Fragment based Screening. AB - We performed a fragment screen on the dengue virus serotype 3 RNA-dependent RNA polymerase using x-ray crystallography. A screen of 1,400 fragments in pools of eight identified a single hit that bound in a novel pocket in the protein. This pocket is located in the polymerase palm subdomain and conserved across the four serotypes of dengue virus. The compound binds to the polymerase in solution as evidenced by surface plasmon resonance and isothermal titration calorimetry analyses. Related compounds where a phenyl is replaced by a thiophene show higher affinity binding, indicating the potential for rational design. Importantly, inhibition of enzyme activity correlated with the binding affinity, showing that the pocket is functionally important for polymerase activity. This fragment is an excellent starting point for optimization through rational structure-based design. PMID- 26872971 TI - Actin Filaments Are Involved in the Coupling of V0-V1 Domains of Vacuolar H+ ATPase at the Golgi Complex. AB - We previously reported that actin-depolymerizing agents promote the alkalization of the Golgi stack and thetrans-Golgi network. The main determinant of acidic pH at the Golgi is the vacuolar-type H(+)-translocating ATPase (V-ATPase), whose V1domain subunitsBandCbind actin. We have generated a GFP-tagged subunitB2construct (GFP-B2) that is incorporated into the V1domain, which in turn is coupled to the V0sector. GFP-B2 subunit is enriched at distal Golgi compartments in HeLa cells. Subcellular fractionation, immunoprecipitation, and inversal FRAP experiments show that the actin depolymerization promotes the dissociation of V1-V0domains, which entails subunitB2translocation from Golgi membranes to the cytosol. Moreover, molecular interaction between subunitsB2andC1and actin were detected. In addition, Golgi membrane lipid order disruption byd-ceramide-C6 causes Golgi pH alkalization. We conclude that actin regulates the Golgi pH homeostasis maintaining the coupling of V1-V0domains of V ATPase through the binding of microfilaments to subunitsBandCand preserving the integrity of detergent-resistant membrane organization. These results establish the Golgi-associated V-ATPase activity as the molecular link between actin and the Golgi pH. PMID- 26872972 TI - Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport. AB - Heat shock protein 90 (HSP90) is a molecular chaperone that is up-regulated in cancer and is required for the folding of numerous signaling proteins. Consequently, HSP90 represents an ideal target for the development of new anti cancer agents. The human HSP90 isoform, glucose-regulated protein 94 (GRP94), resides in the endoplasmic reticulum and regulates secretory pathways, integrins, and Toll-like receptors, which contribute to regulating immunity and metastasis. However, the cellular function of GRP94 remains underinvestigated. We report that GRP94 knockdown cells are defective in intracellular transport and, consequently, negatively impact the trafficking of F-actin toward the cellular cortex, integrin alpha2 and integrin alphaL toward the cell membrane and filopodia, and secretory vesicles containing the HSP90alpha-AHA1-survivin complex toward the leading edge. As a result, GRP94 knockdown cells form a multipolar spindle instead of bipolar morphology and consequently manifest a defect in cell migration and adhesion. PMID- 26872973 TI - Ajuga Delta24-Sterol Reductase Catalyzes the Direct Reductive Conversion of 24 Methylenecholesterol to Campesterol. AB - Dimunito/Dwarf1 (DWF1) is an oxidoreductase enzyme that is responsible for the conversion of C28- and C29-Delta(24(28))-olefinic sterols to 24-methyl- and 24 ethylcholesterols. Generally, the reaction proceeds in two steps via the Delta(24(25))intermediate. In this study, we characterized theArDWF1gene from an expression sequence tag library ofAjuga reptansvar.atropurpureahairy roots. The gene was functionally expressed in the yeast T21 strain. Thein vivoandin vitrostudy of the transformed yeast indicated that ArDWF1 catalyzes the conversion of 24-methylenecholesterol to campesterol. A labeling study followed by GC-MS analysis suggested that the reaction proceeded with retention of the C 25 hydrogen. The 25-H retention was established by the incubation of the enzyme with (23,23,25-(2)H3,28-(13)C)-24-methylenecholesterol, followed by(13)C NMR analysis of the resulting campesterol. Thus, it has been concluded that ArDWF1 directly reduces 24-methylenecholesterol to produce campesterol without passing through a Delta(24(25))intermediate. This is the first characterization of such a unique DWF1 enzyme. For comparison purposes,Oryza sativa DWF1(OsDWF1) was similarly expressed in yeast. Anin vivoassay of OsDWF1 supported the generally accepted two-step mechanism because the C-25 hydrogen of 24-methylenecholesterol was eliminated during its conversion to 24-methylcholesterol. As expected, the 24 methylcholesterol produced by OsDWF1 was a mixture of campesterol and dihydrobrassicasterol. Furthermore, the 24-methylcholesterol contained in theAjugahairy roots was determined to be solely campesterol through its analysis using chiral GC-MS. Therefore, ArDWF1 has another unique property in that only campesterol is formed by the direct reduction catalyzed by the enzyme. PMID- 26872975 TI - Transcription Elongation Factor NusA Is a General Antagonist of Rho-dependent Termination in Escherichia coli. AB - NusA is an essential protein that binds to RNA polymerase and also to the nascent RNA and influences transcription by inducing pausing and facilitating the process of transcription termination/antitermination. Its participation in Rho-dependent transcription termination has been perceived, but the molecular nature of this involvement is not known. We hypothesized that, because both Rho and NusA are RNA binding proteins and have the potential to target the same RNA, the latter is likely to influence the global pattern of the Rho-dependent termination. Analyses of the nascent RNA binding properties and consequent effects on the Rho-dependent termination functions of specific NusA-RNA binding domain mutants revealed an existence of Rho-NusA direct competition for the overlappingnut(NusA-binding site) andrut(Rho-binding site) sites on the RNA. This leads to delayed entry of Rho at therutsite that inhibits the latter's RNA release process. High density tiling microarray profiles of these NusA mutants revealed that a significant number of genes, together with transcripts from intergenic regions, are up regulated. Interestingly, the majority of these genes were also up-regulated when the Rho function was compromised. These results provide strong evidence for the existence of NusA-binding sites in different operons that are also the targets of Rho-dependent terminations. Our data strongly argue in favor of a direct competition between NusA and Rho for the access of specific sites on the nascent transcripts in different parts of the genome. We propose that this competition enables NusA to function as a global antagonist of the Rho function, which is unlike its role as a facilitator of hairpin-dependent termination. PMID- 26872974 TI - Regulation of Monocarboxylic Acid Transporter 1 Trafficking by the Canonical Wnt/beta-Catenin Pathway in Rat Brain Endothelial Cells Requires Cross-talk with Notch Signaling. AB - The transport of monocarboxylate fuels such as lactate, pyruvate, and ketone bodies across brain endothelial cells is mediated by monocarboxylic acid transporter 1 (MCT1). Although the canonical Wnt/beta-catenin pathway is required for rodent blood-brain barrier development and for the expression of associated nutrient transporters, the role of this pathway in the regulation of brain endothelial MCT1 is unknown. Here we report expression of nine members of the frizzled receptor family by the RBE4 rat brain endothelial cell line. Furthermore, activation of the canonical Wnt/beta-catenin pathway in RBE4 cells via nuclear beta-catenin signaling with LiCl does not alter brain endothelialMct1mRNA but increases the amount of MCT1 transporter protein. Plasma membrane biotinylation studies and confocal microscopic examination of mCherry tagged MCT1 indicate that increased transporter results from reduced MCT1 trafficking from the plasma membrane via the endosomal/lysosomal pathway and is facilitated by decreased MCT1 ubiquitination following LiCl treatment. Inhibition of the Notch pathway by the gamma-secretase inhibitorN-[N-(3,5 difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester negated the up regulation of MCT1 by LiCl, demonstrating a cross-talk between the canonical Wnt/beta-catenin and Notch pathways. Our results are important because they show, for the first time, the regulation of MCT1 in cerebrovascular endothelial cells by the multifunctional canonical Wnt/beta-catenin and Notch signaling pathways. PMID- 26872977 TI - Role of oxidative stress on platelet hyperreactivity during aging. AB - Thrombotic events are common causes of morbidity and mortality in the elderly. Age-accelerated vascular injury is commonly considered to result from increased oxidative stress. There is abundant evidence that oxidative stress regulate several components of thrombotic processes, including platelet activation. Thus oxidative stress can trigger platelet hyperreactivity by decreasing nitric oxide bioavailability. Therefore oxidative stress measurement may help in the early identification of asymptomatic subjects at risk of thrombosis. In addition, oxidative stress inhibitors and platelet-derived nitric oxide may represent a novel anti-aggregation/-activation approach. In this article the relative contribution of oxidative stress and platelet activation in aging is explored. PMID- 26872976 TI - Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats. AB - AIM: Rectovaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistula may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas. MAIN METHODS: BPC 157 (10MUg/kg or 10ng/kg) was given perorally, in drinking water (0.16MUg/ml or 0.16ng/ml, 12ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). The assessment (i.e., rectal and vaginal defect, fistula leakage, defecation through the fistula, adhesions and intestinal obstruction as healing processes) was at day 1, 3, 5, 7, 10, 14 and 21. KEY FINDINGS: Regularly, rectovaginal fistulas exhibited poor healing, with both of the defects persisting, continuous fistula leakage, defecation through the fistula, advanced adhesion formation and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally, in MUg- and ng-regimens rapidly improved the whole presentation, with both rectal and vaginal defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised till the values of healthy rats were achieved, there were no signs of defecation through the fistula. A counteraction of advanced adhesion formation and intestinal obstruction was achieved. Microscopic improvement was along with macroscopic findings. SIGNIFICANCE: BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats. PMID- 26872978 TI - Higher mitochondrial potential and elevated mitochondrial respiration are associated with excessive activation of blood platelets in diabetic rats. AB - AIMS: The high glucose concentration observed in diabetic patients is a recognized factor of mitochondrial damage in various cell types. Its impact on mitochondrial bioenergetics in blood platelets remains largely vague. The aim of the study was to determine how the metabolism of carbohydrates, which has been impaired by streptozotocin-induced diabetes may affect the functioning of platelet mitochondria. MATERIALS AND METHODS: Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Platelet mitochondrial respiratory capacity was monitored as oxygen consumption (high resolution respirometry). Mitochondrial membrane potential was assessed using a fluorescent probe, JC-1. Activation of circulating platelets was monitored by flow cytometry measuring of the expressions of CD61 and CD62P on a blood platelet surface. To determine mitochondrial protein density in platelets, Western Blot technique was used. KEY FINDINGS: The results indicate significantly elevated mitochondria mass, increased mitochondrial membrane potential (DeltaPsim) and enhanced respiration in STZ-diabetic animals, although the respiration control ratios appear to remain unchanged. Higher DeltaPsim and elevated mitochondrial respiration were closely related to the excessive activation of circulating platelets in diabetic animals. SIGNIFICANCE: Long-term diabetes can result in increased mitochondrial mass and may lead to hyperpolarization of blood platelet mitochondrial membrane. These alterations may be a potential underlying cause of abnormal platelet functioning in diabetes mellitus and hence, a potential target for antiplatelet therapies in diabetes. PMID- 26872979 TI - MicroRNA-30a promotes chondrogenic differentiation of mesenchymal stem cells through inhibiting Delta-like 4 expression. AB - AIMS: MicroRNAs (miRNAs) play important roles in chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the regulation of miR-30a during such process has not yet been well understood. The aim of the study was to investigate the effects of miR-30a on chondrogenic differentiation of MSCs and explore the underlying mechanisms. MATERIALS AND METHODS: MSCs were isolated from rat bone marrow, and their immunophenotypes and multilineage differentiation potentials were identified. MiR-30a mimics or inhibitor were transfected into rat MSCs and SW1353 cells, respectively, and then the effects of miR-30a on chondrogenic differentiation were detected. The predicted target gene Delta-like 4 (DLL4, a ligand of the Notch signaling family) was verified by luciferase reporter assay, quantitative real time PCR and western blot. KEY FINDINGS: MiR-30a was significantly up-regulated during chondrogenic differentiation of rat MSCs. Additionally, transfection of miR-30a mimics remarkably promoted the differentiation of rat MSCs into chondrocytes as evidence by the notably increased mRNA and protein expression levels of chondrogenic markers Collagen II and aggrecan as well as the enhanced alcian blue staining intensity, whereas inhibition of miR-30a obviously suppressed such process. Furthermore, during chondrogenesis, DLL4 expression was found to significantly decrease at both mRNA and protein levels, which was negatively regulated by miR-30a through directly targeting the 3'UTR of DLL4. SIGNIFICANCE: Our results indicate that miR-30a acts as a key promoter for chondrogenic differentiation of MSCs by down-regulating DLL4 expression, and provide a novel insight on miRNA-mediated MSC therapy for cartilage-related disorders including osteoarthritis. PMID- 26872980 TI - Propentofylline treatment on open field behavior in rats with focal ethidium bromide-induced demyelination in the ventral surface of the brainstem. AB - Propentofylline (PPF) is a xanthine derivative with pharmacological effects that are distinct from those of classic methylxanthines. It depresses the activation of microglial cells and astrocytes, which is associated with neuronal damage during neural inflammation and hypoxia. Our previous studies showed that PPF improved remyelination following gliotoxic lesions that were induced by ethidium bromide (EB). In the present study, the long-term effects of PPF on open field behavior in rats with EB-induced focal demyelination were examined. The effects of PPF were first evaluated in naive rats that were not subjected to EB lesions. Behavior in the beam walking test was also evaluated during chronic PPF treatment because impairments in motor coordination can interfere with behavior in the open field. The results showed that PPF treatment in unlesioned rats decreased general activity and caused motor impairment in the beam walking test. Gliotoxic EB injections increased general activity in rats that were treated with PPF compared with rats that received saline solution. Motor incoordination was also attenuated in PPF-treated rats. These results indicate that PPF reversed the effects of EB lesions on behavior in the open field and beam walking test. PMID- 26872981 TI - Oleuropein activated AMPK and induced insulin sensitivity in C2C12 muscle cells. AB - AIMS: Oleuropein has been recognized as an important medicinal compound because of its various biological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. Here, we evaluate the antioxidant activity as well as the mechanism of the hypoglycemic effects of oleuropein in C2C12 cells and we establish the mechanism underlying these effects. MAIN METHODS: To perform this study, C2C12 cells viability was analyzed via MTT assay and the antioxidant activity was investigated by ROS and TBARS assays. Also, the effect of oleuropein on AMPK and PI3 kinase signaling pathways was evaluated. KEY FINDINGS: Treatment with oleuropein was able to protect cells against H2O2 induced stress in cells. On the other hand, the molecular bases of its actions have been scarcely understood. Oleuropein significantly enhanced glucose consumption and the phosphorylation of AMPK (AMP-activated protein kinase/ACC (acetyl-CoA carboxylase)) and MAPKs (mitogen-activated protein kinases), but not PI3 kinase (Phosphatidylinositol 3-kinase)/Akt. However, the co-treatment of oleuropein and insulin improved the insulin sensitivity via insulin-dependent (PI3 kinase/Akt) and insulin independent (AMPK/ACC) pathways. These results could be confirmed from the findings of GLUT4 translocation which was strongly enhanced in the case of oleuropein. SIGNIFICANCE: Our results provide important insights for the possible mechanism of action of oleuropein as a therapeutic agent in diabetic patients. PMID- 26872982 TI - Increased rho kinase activity in mononuclear cells of dialysis and stage 3-4 chronic kidney disease patients with left ventricular hypertrophy: Cardiovascular risk implications. AB - AIMS: Cardiovascular disease (CVD) is the leading cause of excess mortality in chronic kidney disease (CKD) and dialysis patients (DP) who have higher prevalence of left ventricular hypertrophy (LVH), the strongest predictor of CV events. Rho kinase (ROCK) activation is linked in hypertensive patients to cardiac remodeling while ROCK inhibition suppresses cardiomyocyte hypertrophy and, in a human clinical condition opposite to hypertension, its downregulation associates with lack of CV remodeling. Information on ROCK activation-LVH link in CKD and DP is lacking. MATERIALS AND METHODS: Mononuclear cells (PBMCs) MYPT-1 phosphorylation, a marker of ROCK activity, and the effect of fasudil, a ROCK inhibitor, on MYPT-1 phosphorylation were assessed in 23 DPs, 13 stage 3-4 CKD and 36 healthy subjects (HS) by Western blot. LV mass was assessed by M-mode echocardiography. KEY FINDINGS: DP and CKD had higher MYPT-1 phosphorylation compared to HS (p<0.001 and p=0.003). Fasudil (500 and 1000MUM) dose dependently reduced MYPT-1 phosphorylation in DP (p<0.01). DP had higher LV mass than CKD (p<0.001). MYPT-1 phosphorylation was higher in patients with LVH (p=0.009) and correlated with LV mass both in DP and CKD with LVH (p<0.001 and p=0.006). SIGNIFICANCE: In DP and CKD, ROCK activity tracks with LVH. This ROCK activation LVH link provided in these CVD high-risk patients along with similar findings in hypertensive patients and added to opposite findings in a human model opposite to hypertension and in type 2 diabetic patients, identify ROCK activation as a potential LVH marker and provide further rationale for ROCK activation inhibition as target of therapy in CVD high-risk patients. PMID- 26872983 TI - Pregabalin can prevent, but not treat, cognitive dysfunction following abdominal surgery in aged rats. AB - AIMS: The present study aimed to explore the preventive or therapeutic effect of peri-operative pregabalin treatment on the memory deficits and related hippocampal inflammation following surgery in aged rats. MAIN METHODS: Aged rats underwent abdominal or sham surgery, and were then divided into 2 groups, either early or late pregabalin treatment. Fourteen days after surgery, the cognitive function was assessed using novel object recognition test, followed by measurement of hippocampal cytokines and voltage-dependent calcium channel alpha2delta subunit (CACNA2D1). The parabiotic experiments determined whether the humoral or neuronal pathway was involved in the neuroinflammation development following the abdominal surgery. The effects of pregabalin on LPS-induced cytokine release from hippocampal microglia were also evaluated. KEY FINDINGS: Early pregabalin treatment, which was administered pre-operatively and continued for 3 or 7days after surgery, prevented memory deficits and decreased hippocampal pro-inflammatory cytokine levels. In contrast, no beneficial effects were observed when pregabalin was administered late in the post-operative period. The hippocampal levels of CACNA2D1 did not change under any experimental condition. The data from the cross-circulation (parabiosis) experiments indicated that abdominal surgery may induce neuroinflammation via a neural transmission pathway from the periphery to the brain. The ex vivo experiments further demonstrated that pregabalin had no effect on LPS-induced cytokines release from hippocampal microglia. SIGNIFICANCE: Our findings highlight reveal that peri-operative pregabalin treatment during the early post-operative period can prevent neuroinflammation and memory deficits after surgery. It is likely this occurs through a peripheral and central neuro-immune interaction rather than through direct anti-inflammatory effects. PMID- 26872984 TI - Opisthorchis viverrini infections and associated risk factors in a lowland area of Binh Dinh Province, Central Vietnam. AB - Opisthorchiasis caused by Opisthorchis viverrini is a major public health problem in the Mekong Basin in South East Asia. It is associated with cholangiocarcinoma, a fatal cancer of the bile duct, which is very common in some areas of Thailand and Lao PDR. Although there is evidence of opisthorchiasis in the central and Southern provinces of Vietnam, data are scarce and Vietnam is often not considered an opisthorchiasis endemic area in the international literature. We conducted a cross-sectional survey in June 2015 in a lowland rural area of Binh Dinh Province in Central Vietnam to investigate the apparent prevalence of O. viverrini infection in the population and the associated risk factors. A total of 254 stool samples were collected and examined by the Kato Katz method. Consenting people shedding Opisthorchis-like eggs with their stools were treated with praziquantel and MgSO4 and adult worms were collected from stools for morphological and molecular identifications. Risk factors were studied with a structured questionnaire and the association with infection was evaluated by univariate and multivariate Firth's logistic regression analysis. The apparent prevalence in the investigated population determined by stool examination was 11.4% (CI: 8-16%). Infection with O. viverrini was confirmed in all 11 individuals consenting to receive praziquantel treatment and subsequent worm recovery from stools. The mean number of worms recovered after treatment/purgation was 14.5 (range 2-44). Male gender and the consumption of dishes prepared from raw small wild-caught freshwater fish (Carassius auratus) were found to be significant risk factors associated with opisthorchiasis in the area. These findings confirm the presence of O. viverrini infection in Central Vietnam related to the consumption of raw fish dishes. Awareness campaigns and control programs should be implemented in the region to combat this potentially fatal fluke infection. PMID- 26872985 TI - Effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 on the left ventricular pressure-volume relationship in the halothane-anesthetized dogs. AB - Cardiac effects of a prostagrandin EP4-receptor agonist ONO-AE1-329 were assessed in the halothane-anesthetized dogs under the monitoring of left ventricular pressure-volume relationship, which were compared with those of clinically recommended doses of dopamine, dobutamine and milrinone (n=4-5 for each treatment). ONO-AE1-329 was intravenously administered in doses of 0.3, 1 and 3 ng/kg/min for 10 min with a pause of 20 min. Dopamine in a dose of 3 ug/kg/min for 10 min, dobutamine in a dose of 1 ug/kg/min for 10 min and milrinone in a dose of 5 ug/kg/min for 10 min followed by 0.5 ug/kg/min for 10 min were intravenously administered. Low dose of ONO-AE1-329 increased the stroke volume. Middle dose of ONO-AE1-329 increased the cardiac output, left ventricular end diastolic volume, ejection fraction, maximum upstroke/downstroke velocities of the left ventricular pressure and external work, but decreased the end-systolic pressure and internal work besides the change by the low dose. High dose of ONO AE1-329 increased the heart rate and maximum elastance, but decreased the end systolic volume besides the changes by the middle dose. Dopamine, dobutamine and milrinone exerted essentially similar cardiac effects to ONO-AE1-329, but they did not significantly change the end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, end-systolic pressure, maximum elastance, external work or internal work. Thus, EP4-receptor stimulation by ONO-AE1-329 may have potential to better promote the passive ventricular filling than the conventional cardiotonic drugs, which could become a candidate of novel therapeutic strategy for the treatment of heart failure with preserved ejection fraction. PMID- 26872986 TI - Ambroxol inhalation ameliorates LPS-induced airway inflammation and mucus secretion through the extracellular signal-regulated kinase 1/2 signaling pathway. AB - Ambroxol, a metabolite of bromhexine, is shown to exert several pharmacological activities, including secretolytic, anti-inflammatory and antioxidant actions. Oral and intravenous administration of ambroxol is useful for the airway inflammatory diseases. However, little is known about its potential in inhalation therapy for lipopolysaccharide (LPS)-induced mucous hypersecretion and inflammatory response. In the present study, we compared the pharmacological effects of ambroxol by inhalation with intravenous administration and preliminarily explored its mechanism of action. Our results demonstrated that ambroxol administered by inhalation inhibited MUC5AC expression, reduced glycosaminoglycan levels, enhanced the function of mucociliary clearance and promoted sputum excretion, suggesting that ambroxol increases expectoration of sputum by reducing its viscosity. Moreover, ambroxol significantly alleviated LPS induced the influx of inflammatory cells and the extracellular signal-regulated kinase 1/2 (Erk 1/2) expression in lung tissues, and inhibited increases in the mRNA expression of the pro-inflammatory cytokines tumor necrosis factor (TNF) alpha, CCL-2 (monocyte chemotactic protein-1), KC (keratinocyte cell protein) and interleukin (IL)-1beta in lung tissues. The secretolytic and anti-inflammatory effects of inhaled ambroxol at a dose of 7.5 mg/ml was comparable to that of ambroxol at 20 mg/ml i.v. and dexamethasone at 0.5 mg/kg i.p. In addition, we found that ambroxol dose-dependently inhibited LPS-induced increases in the mRNA expression of MUC5AC, TNF-alpha, and IL-1beta in human bronchial epithelial cell (NCI-H292) by inhibiting the Erk signaling pathway. These results demonstrate the beneficial effects of ambroxol in inhalation therapy for the airway inflammatory diseases. PMID- 26872987 TI - Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors. AB - Meprobamate is a schedule IV anxiolytic and the primary metabolite of the muscle relaxant carisoprodol. Meprobamate modulates GABAA (gamma-aminobutyric acid Type A) receptors, and has barbiturate-like activity. To gain insight into its actions, we have conducted a series of studies using recombinant GABAA receptors. In alphaxbetazgamma2 GABAA receptors (where x=1-6 and z=1-3), the ability to enhance GABA-mediated current was evident for all alpha subunit isoforms, with the largest effect observed in alpha5-expressing receptors. Direct gating was present with all alpha subunits, although attenuated in alpha3-expressing receptors. Allosteric and direct effects were comparable in alpha1beta1gamma2 and alpha1beta2gamma2 receptors, whereas allosteric effects were enhanced in alpha1beta2 compared to alpha1beta2gamma2 receptors. In "extrasynaptic" (alpha1beta3delta and alpha4beta3delta) receptors, meprobamate enhanced EC20 and saturating GABA currents, and directly activated these receptors. The barbiturate antagonist bemegride attenuated direct effects of meprobamate. Whereas pentobarbital directly gated homomeric beta3 receptors, meprobamate did not, and instead blocked the spontaneously open current present in these receptors. In wild type homomeric rho1 receptors, pentobarbital and meprobamate were ineffective in direct gating; a mutation known to confer sensitivity to pentobarbital did not confer sensitivity to meprobamate. Our results provide insight into the actions of meprobamate and parent therapeutic agents such as carisoprodol. Whereas in general actions of meprobamate were comparable to those of carisoprodol, differential effects of meprobamate at some receptor subtypes suggest potential advantages of meprobamate may be exploited. A re-assessment of previously synthesized meprobamate-related carbamate molecules for myorelaxant and other therapeutic indications is warranted. PMID- 26872989 TI - Cross-talk between 5-hydroxytryptamine and substance P in the melanogensis and apoptosis of B16F10 melanoma cells. AB - Skin pigmentation is a complex process controlled by many different factors. Substance P (SP) regulates many biological functions, including melanogenesis and stress. Our previous study indicated that regulation of SP on melanocyte function was mediated by neurokinin 1 receptor (NK1 receptor). Substantial evidence has accumulated that psychological stress can be associated with skin pigmentation, so that the impact of 5-hydroxytryptamine (5-HT), one of the important factors participating in stress process, on melanogenesis has also been concerned. It has been reported that 5-HT induces melanin synthesis via 5-HT2A receptor. Furthermore, 5-HT2A receptor and NK1 receptor are G-protein coupled receptors (GPCRs) and both expressed on melanocyte, the present study was designed to investigate whether SP has influence on the adjustment function of 5-HT. Our data demonstrated that, SP inhibited 5-HT2A receptor expression to neutralize the pro melanogenesis effect of 5-HT on B16F10 cells. The up-regulation of NK1 receptor expression was simultaneous with the down-regulation of 5-HT2A receptor treated by SP. This inhibition of 5-HT2A receptor expression by SP could be reversed by NK1 receptor antagonist Spantide I. Our studies indicated that SP could directly induce B16F10 cells apoptosis in vitro. 5-HT and 5-HT2A receptor agonist could mitigate this apoptotic effect of SP. It is the strong evidence of possible cross talk between GPCRs and giving enlightenments when screening desirable drugs for target receptors. PMID- 26872988 TI - Novel effects of FTY720 on perinuclear reorganization of keratin network induced by sphingosylphosphorylcholine: Involvement of protein phosphatase 2A and G protein-coupled receptor-12. AB - Sphingosylphosphorylcholine (SPC) evokes perinuclear reorganization of keratin 8 (K8) filaments and regulates the viscoelasticity of metastatic cancer cells leading to enhanced migration. Few studies have addressed the compounds modulating the viscoelasticity of metastatic cancer cells. We studied the effects of sphingosine (SPH), sphingosine 1-phosphate (S1P), FTY720 and FTY720-phosphate (FTY720P) on SPC-induced K8 phosphorylation and reorganization using Western blot and confocal microscopy, and also evaluated the elasticity of PANC-1 cells by atomic force microscopy. FTY720, FTY720P, SPH, and S1P concentration-dependently inhibited SPC-evoked phosphorylation and reorganization of K8, and migration of PANC-1 cells. SPC triggered reduction and narrow distribution of elastic constant K and conversely, FTY720 blocked them. A common upstream regulator of JNK and ERK, protein phosphatase 2A (PP2A) expression was reduced by SPC, but was restored by FTY720 and FTY72P. Butyryl forskolin, a PP2A activator, suppressed SPC-induced K8 phosphorylation and okadaic acid, a PP2A inhibitor, induced K8 phosphorylation. Gene silencing of PP2A also led to K8 phosphorylation, reorganization and migration. We also investigated the involvement of GPR12, a high-affinity SPC receptor, in SPC-evoked keratin phosphorylation and reorganization. GPR12 siRNA suppressed the SPC-triggered phosphorylation and reorganization of K8. GPR12 overexpression stimulated keratin phosphorylation and reorganization even without SPC. FTY720 and FTY720P suppressed the GPR12-induced phosphorylation and reorganization of K8. The collective data indicates that FTY720 and FTY720P suppress SPC-induced phosphorylation and reorganization of K8 in PANC-1 cells by restoring the expression of PP2A via GPR12. These findings might be helpful in the development of compounds that modulate the viscoelasticity of metastatic cancer cells and various SPC actions. PMID- 26872990 TI - Oleuropein, a natural extract from plants, offers neuroprotection in focal cerebral ischemia/reperfusion injury in mice. AB - Oleuropein (OLE) was found to have anti-inflammatory and anti-oxidant effects. The latest study has shown that it can resist myocardial injury that follows an acute myocardial infarction and can rescue impaired spinal nerve cells. In this study, we investigated the neuroprotective effects of OLE on cerebral ischemia and reperfusion injury in a middle cerebral artery occlusion model in mice.OLE (100 mg/kg) was injected intraperitoneally 1h before ischemia. We found that the volume of cerebral infarction was significantly reduced after 75 min of ischemia and 24 h of reperfusion compared with the I/R (ischemia/reperfusion) group. This protective function occurred in a dose-dependent manner. We also found that treatment with OLE could reduce the cerebral infarct volume. The neuroprotective effect was prolonged from 2 h to 4 h when we injected OLE intracerebroventricularly after reperfusion. We then found that OLE can decrease the level of cleavedcaspase-3, an important marker of apoptosis, in the ischemic mouse brain. Finally, we explored the role of OLE in providing anti-apoptotic effects through the increased expression of Bcl-2 and the decreased expression of Bax, which are important markers in apoptosis. As shown above, the function and safety of OLE in cardiovascular disease may indicate that it is a potential therapeutic for stroke. PMID- 26872991 TI - Biphasic cardiovascular and respiratory effects induced by beta-citronellol. AB - beta-Citronellol is a monoterpene found in the essential oil of various plants with antihypertensive properties. In fact, beta-citronellol possesses hypotensive actions due to its vasodilator abilities. Here we aimed to show that beta citronellol recruits airway sensory neural circuitry to evoke cardiorespiratory effects. In anesthetized rats, intravenous injection of beta-citronellol caused biphasic hypotension, bradycardia and apnea. Bilateral vagotomy, perivagal capsaicin treatment or injection into the left ventricle abolished first rapid phase (named P1) but not delayed phase P2 of the beta-citronellol effects. P1 persisted after pretreatment with capsazepine, ondansetron, HC-030031 or suramin. Suramin abolished P2 of apnea. In awake rats, beta-citronellol induced biphasic hypotension and bradycardia being P1 abolished by methylatropine. In vitro, beta citronellol inhibited spontaneous or electrically-evoked contractions of rat isolated right or left atrium, respectively, and fully relaxed sustained contractions of phenylephrine in mesenteric artery rings. In conclusion, chemosensitive pulmonary vagal afferent fibers appear to mediate the cardiovascular and respiratory effects of beta-citronellol. The transduction mechanism in P1 seems not to involve the activation of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential ankyrin subtype 1 (TRPA1), purinergic (P2X) or 5-HT3 receptors located on airways sensory nerves. P2 of hypotension and bradycardia seems resulting from a cardioinhibitory and vasodilatory effect of beta-citronellol and the apnea from a purinergic signaling. PMID- 26872992 TI - Non-muscle myosin light chain promotes endothelial progenitor cells senescence and dysfunction in pulmonary hypertensive rats through up-regulation of NADPH oxidase. AB - Non-muscle myosin regulatory light chain (nmMLC20) is reported to exert transcriptional function in regulation of gene expression, and NADPH oxidase (NOX)-derived reactive oxygen species contribute to vascular remodeling of pulmonary artery hypertension (PAH). This study aims to determine if nmMLC20 can promote endothelial progenitor cells (EPCs) senescence and dysfunction through up regulation of NOX in PAH rats. The rats were exposed to10% hypoxia for 3 weeks to establish a PAH model, which showed an increase in right ventricle systolic pressure, right ventricular and pulmonary vascular remodeling, and the accelerated senescence and impaired functions in EPCs, accompanied by an increase in Rho-kinase (ROCK) and NOX activities, p-nmMLC20 level, NOX expression and H2O2 content; these phenomena were reversed by fasudil, a selective inhibitor of ROCK. Next, normal EPCs were cultured under hypoxia to induce senescence in vitro. Consistent with the in vivo findings, hypoxia increased the senescence and dysfunction of EPCs concomitant with an increase in ROCK and NOX activities, p nmMLC20 level, NOX expression and H2O2 content; these phenomena were reversed by fasudil. Knockdown of nmMLC20 showed similar results to that of fasudil except no effect on ROCK activity. Based on these observations, we conclude that nmMLC20 could promote the senescence and dysfunctions of EPCs in PAH through up regulation of NOX in a phosphorylation-dependent manner. PMID- 26872993 TI - ORM-3819 promotes cardiac contractility through Ca(2+) sensitization in combination with selective PDE III inhibition, a novel approach to inotropy. AB - This study is the first pharmacological characterization of the novel chemical entity, ORM-3819 (L-6-{4-[N'-(4-Hydroxi-3-methoxy-2-nitro-benzylidene)-hydrazino] phenyl}-5-methyl-4,5-dihydro-2H-pyridazin-3-one), focusing primarily on its cardiotonic effects. ORM-3819 binding to cardiac troponin C (cTnC) was confirmed by nuclear magnetic resonance spectroscopy, and a selective inhibition of the phosphodiesterase III (PDE III) isozyme (IC50=3.88+/-0.3 nM) was revealed during in vitro enzyme assays. The Ca(2+)-sensitizing effect of ORM-3819 was demonstrated in vitro in permeabilized myocyte-sized preparations from left ventricles (LV) of guinea pig hearts (DeltapCa50=0.12+/-0.01; EC50=2.88+/-0.14 uM). ORM-3819 increased the maximal rate of LV pressure development (+dP/dtmax) (EC50=8.9+/-1.7 nM) and LV systolic pressure (EC50=7.63+/-1.74 nM) in Langendorff perfused guinea pig hearts. Intravenous administration of ORM-3819 increased LV+dP/dtmax (EC50=0.13+/-0.05 uM/kg) and improved the rate of LV pressure decrease (-dP/dtmax); (EC50=0.03+/-0.02 uM/kg) in healthy guinea pigs. In an in vivo dog model of myocardial stunning, ORM-3819 restored the depressed LV+dP/dtmax and improved % segmental shortening (%SS) in the ischemic area (to 18.8+/-3), which was reduced after the ischaemia-reperfusion insult (from 24.1+/ 2.1 to 11.0+/-2.4). Our data demonstrate ORM-3819 as a potent positive inotropic agent exerting its cardiotonic effect by a cTnC-dependent Ca(2+)-sensitizing mechanism in combination with the selective inhibition of the PDE III isozyme. This dual mechanism of action results in the concentration-dependent augmentation of the contractile performance under control conditions and in the postischemic failing myocardium. PMID- 26872994 TI - Osmoregulation in larvae and juveniles of two recently separated Macrobrachium species: Expression patterns of ion transporter genes. AB - In this comparative study, osmoregulatory mechanisms were analyzed in two closely related species of palaemonid shrimp from Brazil, Macrobrachium pantanalense and Macrobrachium amazonicum. A previous investigation showed that all postembryonic stages of M. pantanalense from inland waters of the Pantanal are able to hyper osmoregulate in fresh water, while this species was not able to hypo-osmoregulate at high salinities. In M. amazonicum originating from the Amazon estuary, in contrast, all stages are able to hypo-osmoregulate, but only first-stage larvae, late juveniles and adults are able to hyper-osmoregulate in fresh water. The underlying molecular mechanisms of these physiological differences have not been known. We therefore investigated the expression patterns of three ion transporters (NKA alpha-subunit, VHA B-subunit and NHE3) following differential salinity acclimation in different ontogenetic stages (stage-V larvae, juveniles) of both species. Larval NKAalpha expression was at both salinities significantly higher in M. pantanalense than in M. amazonicum, whereas no difference was noted in juveniles. VHA was also more expressed in larvae of M. pantanalense than in those of M. amazonicum. When NHE3 expression is compared between the larvae of the two species, further salinity-related differences were observed, with generally higher expression in the inland species. Overall, a high expression of ion pumps in M. pantanalense suggests an evolutionary key role of these transporters in freshwater invasion. PMID- 26872995 TI - Morphological and metabolic adjustments in the small intestine to energy demands of growth, storage, and fasting in the first annual cycle of a hibernating lizard (Tupinambis merianae). AB - Seasonal plasticity in the small intestine of neonatal tegu lizards was investigated using morphometry and analysis of enzymes involved in supplying energy to the intestinal tissue. In the autumn, the intestinal mass (Mi) was 1.0% of body mass and the scaling exponent b=0.92 indicated that Mi was larger in smaller neonates. During arousal from dormancy Mi was 23% smaller; later in spring, Mi increased 60% in relation to the autumn and the exponent b=0.14 indicated that the recovery was disproportionate in smaller tegus. During the autumn, the intestinal villi were greatly elongated; by midwinter, the Hv, SvEp, and VvEp were smaller than during the autumn (59%, 54%, 29%) and were restored to autumn levels during spring. In the active tegus, the maximum activity (Vmax) of enzymes indicated that the enterocytes can obtain energy from different sources, and possess gluconeogenic capacity. During winter, the Vmax of CS, HOAD, GDH, PEPCK was 40-50% lower in relation to the autumn and spring, while the Vmax of HK, PK, LDH, AST was unchanged. The hypoglycemia and the mucosal atrophy/ischemia during winter would prevent the enterocytes from using glucose, whereas they could slowly oxidize fatty acids released from body stores and amino acids from the tissue proteolysis to satisfy their needs of energy. Contrastingly, starvation during spring caused severe mass loss (50%); the tissue protein and the VvEp and VvLP did not change while the thickness of the muscular layer increased 51%, which suggested different effects along the length of the organ. In addition, the Vmax of the glycolytic enzymes was lower, indicating that a regulatory mechanism would spare blood glucose for vital organs during unanticipated food restriction. PMID- 26872996 TI - Ammonia excretion in Caenorhabditis elegans: Physiological and molecular characterization of the rhr-2 knock-out mutant. AB - Previous studies have shown the free living soil nematode Caenorhabditis elegans (N2 strain) to be ammonotelic. Ammonia excretion was suggested to take place partially via the hypodermis, involving the Na(+)/K(+)-ATPase (NKA), V-ATPase (VAT), carbonic anhydrase, NHX-3 and a functional microtubule network and at least one Rh-like ammonia transporter RHR-1. In the current study, we show that a second Rh-protein, RHR-2, is highly expressed in the hypodermis, here also in the apical membrane of that tissue. To further characterize the role of RHR-2 in ammonia excretion, a knock-out mutant rhr-2 (ok403), further referred to as ?rhr 2, was employed. Compared to wild-type worms (N2), this mutant showed a lower rate of ammonia excretion and a lower hypodermal H(+) excretion rate. At the same time rhr-1, nka, vat, and nhx-3 showed higher mRNA expression levels when compared to N2. Also, in contrast to N2 worms, ?rhr-2 did not show enhanced ammonia excretion rates when exposed to a low pH environment, suggesting that RHR 2 represents the apical NH3 pathway that allows ammonia trapping via the hypodermis in N2 worms. A hypothetical model for the mechanism of hypodermal ammonia excretion is proposed on the basis of data in this and previous investigations. PMID- 26872997 TI - Locking compression plate versus revision-prosthesis for Vancouver type B2 periprosthetic femoral fractures after total hip arthroplasty. AB - INTRODUCTION: Revision arthroplasty is currently the recommended treatment for periprosthetic femoral fractures after primary total hip arthroplasty (THA) and stem loosening (Vancouver B2). However, open reduction and internal fixation (ORIF) utilizing locking compression plate (LCP) might be an effective treatment with a reduced surgical time and less complex procedure in a typically elderly patient collective with multiple comorbidities. The purpose of this study was to compare the functional and radiographic outcomes in two cohorts with Vancouver B2 periprosthetic femoral fractures after primary THA, treated either by ORIF with LCP fixation, or by revision arthroplasty utilizing a non-cemented long femoral stem. MATERIALS AND METHODS: 36 patients with Vancouver B2 periprosthetic femoral fractures following THA, who had been treated between 2000 and 2014, were reviewed. Eight fractures were treated with LCP fixation, fourteen fractures with the first-generation revision prosthesis (Helios), and fourteen fractures with the second-generation revision prosthesis (Hyperion). The patients were assessed clinically with the Parker mobility score and radiographically. RESULTS: A total of ten males and 26 females formed the basis of this report with an average age of 81 years (range, 64 to 96 years). All fractures treated with LCP fixation alone healed uneventfully and there were no signs of secondary stem migration, malalignement or plate breakage. The average surgical time was shorter in the ORIF cohort; however, the results were not statistically significant. The postoperative Parker mobility score at latest follow-up showed no difference between the groups. CONCLUSIONS: According to the results of the current study, we conclude that the use of LCP fixation can be a sufficient option for the treatment of Vancouver B2 periprosthetic femoral fractures correspondingly with femoral stem loosening. PMID- 26872998 TI - Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability. AB - Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) exhibit considerable trial-to-trial variability, potentially reducing the sensitivity and reproducibility of this measure. While increasing the number of trials will improve accuracy, prolonged recording blocks are not always feasible. In this study, we investigated the minimum number of trials required to provide a measure of human corticospinal excitability that is stable both within and between sessions. Single-pulse TMS was applied to the left primary motor cortex, and MEPs were recorded from the right first dorsal interosseous muscle. Approximately 20-30 trials were required to provide a stable measure of MEP amplitude with high within- and between-session reliability. Extending the number of trials beyond 30 provided no additional benefit. Collecting 30 trials may be optimal for reliably estimating corticospinal excitability using TMS. These findings may have significant implications for using TMS to measure corticospinal excitability in both basic and clinical research settings. PMID- 26872999 TI - Effects of maternal stress and perinatal fluoxetine exposure on behavioral outcomes of adult male offspring. AB - Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. METHODS: C57BL/6 dams exposed to chronic unpredictable stress from embryonic (E) day 4 to E18 and non stressed dams were administered Flx (25 mg/kg/d) in the drinking water from E15 to postnatal day 12. A separate control group consisted of animals that were not exposed to stress or Flx. At 12 days of age, brain levels of serotonin were assessed in the male offspring. At two months of age, the male offspring of mothers exposed to prenatal stress (PS), perinatal Flx, PS and Flx, or neither PS or Flx, went through a comprehensive behavioral test battery. At the end of testing brain-derived neurotropic factor (BDNF) levels were assessed in the frontal cortex of the offspring. RESULTS: Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive abilities, memory, sensorimotor information processing, or risk assessment behaviors. These results demonstrate that maternal exposure to stress and Flx have a number of sustained effects on the male offspring. PMID- 26873000 TI - The effect of surgical and psychological stress on learning and memory function in aged C57BL/6 mice. AB - Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. We therefore established a pre-clinical model in aged C57BL/6 mice and aimed to investigate the effects of surgical stress and psychological stress on learning and memory function and the possible roles of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. The surgical stress was induced by abdominal surgery under local anesthesia, and the psychological stress was induced by a communication box. Cognitive functions and markers of the AKT/mTOR pathway were assessed at 1, 3 and 7 days following the stress. The impairments of learning and memory function existed for up to 7 days following surgical stress and surgical stress plus psychological stress, whereas the psychological stress did not affect the cognitive function alone or combined with surgical stress. Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD. PMID- 26873001 TI - Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia. AB - BACKGROUND AND PURPOSE: The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used. METHODS: Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively. RESULTS: Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl 16:0/18:1) in the subacute to chronic phases. CONCLUSIONS: Histopathology and IMS can provide comprehensive and complementary information on cell death mechanisms in the hippocampal CA1 after global ischemia. IMS provided novel data on molecular changes in phospholipids immediately after TGI. Increased level of PC (diacyl-16:0/22:6) in the pyramidal cell layer of hippocampal CA1 prior to the histopathological change may represent an early step in delayed neuronal death mechanisms. PMID- 26873003 TI - A Critical Evaluation of Pharmacogenetic Information in Package Inserts for Selected Drugs Marketed in India and Its Comparison With US FDA-Approved Package Inserts. AB - Our objective was to compare the pharmacogenetic information provided in the package inserts (PIs) of 7 drugs marketed in the United States and India, namely, abacavir, capecitabine, carbamazepine, clopidogrel, irinotecan, valproic acid, and warfarin. We evaluated the pharmacogenetic information provided in Indian PIs for the highest level where it was included, robustness and completeness, clinical validity, and clinical utility and compared it with corresponding data of US PIs. Pharmacogenetic studies carried out in India were identified using PubMed. Pharmacogenetic information was provided in Indian PIs of all the drugs except irinotecan. It appeared in the same section as in US PIs for abacavir, capecitabine, carbamazepine (HLA-*3101), valproic acid (urea cycle disorders), and warfarin (protein C and protein S), whereas it appeared at lower levels for other drug-gene combinations. The robustness of pharmacogenetic testing was graded convincing for abacavir, adequate for carbamazepine and clopidogrel, and incomplete for the remaining drugs, and only abacavir and clopidogrel PIs provided full details of supporting studies. These details, when provided in the Indian PIs were identical to those in the US PIs. The Indian PIs did not provide data on Indian patients, although published studies are available. Both US and Indian PIs lacked critical information on the clinical validity and utility of pharmacogenetic testing. The pharmacogenetic information should provide country/ethnicity-specific data so that they are useful to clinicians. Where data are not available, the prevalence of genetic variation in the population of a country needs to be determined and should then be translated to the PIs. PMID- 26873002 TI - Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats. AB - The prefrontal cortex (PFC) is critical for the ability to flexibly adapt established patterns of behavior in response to a change in environmental contingencies. Impaired behavioral flexibility results in maladaptive strategies such as perseveration on response options that no longer produce a desired outcome. Pharmacological manipulations of prefrontal cortical GABAergic signaling modulate behavioral flexibility in animal models, and prefrontal cortical interneuron dysfunction is implicated in impaired behavioral flexibility that accompanies neuropsychiatric disease. As deficits in behavioral flexibility also emerge during the normal aging process, the goal of this study was to determine the role of GABAergic signaling, specifically via prefrontal cortical GABA(B) receptors, in such age-related deficits. Young and aged rats were trained in a set shifting task performed in operant chambers. First, rats learned to discriminate between two response levers to obtain a food reward on the basis of a cue light illuminated above the correct lever. Upon acquisition of this initial discrimination, the contingencies were shifted such that rats had to ignore the cue light and respond on the levers according to their left/right positions. Both young and aged rats acquired the initial discrimination similarly; however, aged rats were impaired relative to young following the set shift. Among aged rats, GABA(B) receptor expression in the medial prefrontal cortex (mPFC) was strongly correlated with set shifting, such that lower expression was associated with worse performance. Subsequent experiments showed that intra-mPFC administration of the GABA(B) receptor agonist baclofen enhanced set shifting performance in aged rats. These data directly link GABAergic signaling via GABA(B) receptors to impaired behavioral flexibility associated with normal aging. PMID- 26873005 TI - Erratum to: Phospholipase C-eta2 interacts with nuclear and cytoplasmic LIMK-1 during retinoic acid-stimulated neurite growth. PMID- 26873004 TI - From lizard body form to serpentiform morphology: The atlas-axis complex in African cordyliformes and their relatives. AB - The comparative vertebral morphology of the atlas-axis complex in cordyliforms, xantusiid and several skinks is studied here. These lizards are particularly interesting because of their different ecological adaptations and anti-predation strategies, where conformation ranges from the lizard-like body to a snake-like body. This transition to serpentiform morphology shows several evolutionary patterns in the atlas-axis complex: 1) the zygapophyseal articulations are lost in the early stage of the transition. In contrast to mammals, the atlas is more or less locked to the axis in lepidosaurs, but the absence of zygapophyseal articulation releases this locking for rotation. However despite its serpentiform morphology, Chamaesaura is different, in possessing this articulation; 2) the first intercentrum of Chamaesaura and Tetradactylus africanus (serpentiform grass swimmers) is fully curved anteriorly, underlying the occipital condyle. While this limits ventral skull rotation beyond a certain angle, it locks the skull, which is a crucial adaptation for a sit-and-wait position in grassland habitats that needs to keep the head stabilized; and 3) in Acontias, most of the atlas articular surface with the occipital condyle is formed by the lateral aspect of the articulation area relative to the area located in the dorsal region of the slightly reduced intercentrum. A similar state occurs in amphisbaenians, most likely reflecting a fossorial lifestyle of the limbless lizards. Although Chamaesaura and Tetradactylus live sympatrically in grasslands, Chamaesaura differs in several ways in atlas-axis complex: for example, aforementioned presence of the atlas-axis zygapophyseal articulation, and long posterodorsal processes. Its occipital condyle protrudes further posteriorly, placing the atlas axis complex further from the endocranium than in Tetradactylus. Hence, adaptation in the same niche, even among sister clades, can lead to different atlas-axis morphology due to different lifestyle strategies, for example, different foraging mode, while similar atlas-axis morphology can evolve in two lineages occupying different niches, as in Ablepharus and Scelotes. PMID- 26873006 TI - Effects of gastric pH on oral drug absorption: In vitro assessment using a dissolution/permeation system reflecting the gastric dissolution process. AB - The aim of the present study was to evaluate the effects of gastric pH on the oral absorption of poorly water-soluble drugs using an in vitro system. A dissolution/permeation system (D/P system) equipped with a Caco-2 cell monolayer was used as the in vitro system to evaluate oral drug absorption, while a small vessel filled with simulated gastric fluid (SGF) was used to reflect the gastric dissolution phase. After applying drugs in their solid forms to SGF, SGF solution containing a 1/100 clinical dose of each drug was mixed with the apical solution of the D/P system, which was changed to fasted state-simulated intestinal fluid. Dissolved and permeated amounts on applied amount of drugs were then monitored for 2h. Similar experiments were performed using the same drugs, but without the gastric phase. Oral absorption with or without the gastric phase was predicted in humans based on the amount of the drug that permeated in the D/P system, assuming that the system without the gastric phase reflected human absorption with an elevated gastric pH. The dissolved amounts of basic drugs with poor water solubility, namely albendazole, dipyridamole, and ketoconazole, in the apical solution and their permeation across a Caco-2 cell monolayer were significantly enhanced when the gastric dissolution process was reflected due to the physicochemical properties of basic drugs. These amounts resulted in the prediction of higher oral absorption with normal gastric pH than with high gastric pH. On the other hand, when diclofenac sodium, the salt form of an acidic drug, was applied to the D/P system with the gastric phase, its dissolved and permeated amounts were significantly lower than those without the gastric phase. However, the oral absorption of diclofenac was predicted to be complete (96-98%) irrespective of gastric pH because the permeated amounts of diclofenac under both conditions were sufficiently high to achieve complete absorption. These estimations of the effects of gastric pH on the oral absorption of poorly water soluble drugs were consistent with observations in humans. In conclusion, the D/P system with the gastric phase may be a useful tool for better predicting the oral absorption of poorly water-soluble basic drugs. In addition, the effects of gastric pH on the oral absorption of poorly water-soluble drugs may be evaluated by the D/P system with and without the gastric phase. PMID- 26873007 TI - [Recurrent hypoglycemia due to an occult insulinoma]. AB - A 64-year-old woman presented with a history of recurrent hypoglycemia. A prolonged fasting test revealed an increased "amended" insulin-glucose ratio. Transabdominal ultrasound (US), computed tomography (CT) scan, and magnetic resonance imaging (MRI) did not show abnormal results. An insulinoma was suspected based on a contrast-enhanced endoscopic US examination as well as a (68)gallium-DOTA-exendin-4 positron-emission tomography (PET)/CT. The diagnosis of an insulinoma was confirmed histologically after surgical removal of the tumor. Hypoglycemia did not occur during the postoperative period. The prolonged fasting test is the gold standard for the diagnosis of an insulinoma. Novel imaging procedures, such as contrast-enhanced endoscopic US or (68)gallium-DOTA exendin-4 PET/CT are valuable additions to the diagnostic workup. PMID- 26873008 TI - Granulomatosis with polyangiitis mimicking classic inflammatory bowel disease associated pyoderma gangrenosum. PMID- 26873009 TI - Comments on: titanium mesh in reconstructive surgery of the nasal pyramid. Follow up of our 11 initial cases. PMID- 26873010 TI - Ex vivo comparison of angioscopy and histopathology for the evaluation of coronary plaque characteristics. AB - The yellow plaque has been considered to be a vulnerable and high risk for acute coronary syndrome events but not fully evaluated. The aim of this study was to evaluate the relationship between angioscopic color grade and histological features in coronary autopsy specimens. We longitudinally sectioned 110 coronary arteries from 40 autopsy hearts with non-cardiovascular death. Harvested arteries were imaged with intravascular ultrasound to identify the focal plaque (plaque burden >50 %). An angioscopic examination of each focal plaque evaluated its color intensity as follows: 0 (white), 1 (light yellow), 2 (yellow), or 3 (dark yellow). The corresponding histological assessment was classified according to a modified version of the American Heart Association classification of atherosclerosis. Two hundred six plaques were matched to the histological analysis. Of these, 82 (40 %) were categorized as yellow (>=grade 1). Although, yellow plaque often includes thin-cap fibroatheroma (TCFA), the sensitivity, specificity, positive predictive value, negative predictive value, and overall diagnostic accuracy for histological TCFA were 83, 91, 22, 99 and 91 %, respectively. The false-positive coronary angioscopic diagnoses for TCFA that contributed to the low positive predictive value consisted of the following plaques: thick FA (>65 MUm), accumulations of large quantities of foam cells on the luminal surface, or dense calcified plates at the surface of the intima. Vulnerable coronary plaques were detected with high sensitivity and low positive predictive value from their yellow color on angioscopy. Not only fibroatheroma but also various types of plaques and their components, such as immature lipidic components and superficial calcium plates, appeared yellow on coronary angioscopy. PMID- 26873012 TI - A Comprehensive Evaluation of a Universal School-Based Depression Prevention Program for Adolescents. AB - The present study proposes and demonstrates a comprehensive framework for evaluation of a universal school-based depression prevention program. Efficacy was evaluated by considering the impact of continuous versus categorical approaches to operationalizing outcome, the effect of the intervention on key change agent variables, and moderation of intervention effects by student symptom severity at baseline. Participants 252 adolescent boys and girls (60 % male), aged 13 to 17 years (M = 13.62 years, SD = 0.60 years) from four schools in the state of Victoria, Australia, who were allocated by school into a waitlist = control (n = 88) or a CBT-based intervention (n = 164) group. The intervention involved six 45-min weekly sessions run during wellbeing classes. While the intervention and control groups did not differ in average improvement in symptoms by post-intervention, further analyses showed that responsiveness was highly variable within the intervention, and those with elevated depressive symptoms benefitted most. The proposed change agents of self-esteem, resilience, body image satisfaction, and perceived social support did not uniquely predict change in depressive symptoms but collectively accounted for substantial variance in this change process. Collectively, this framework provided insights into aspects of the intervention that worked and highlighted areas for improvement, thus providing clear direction for future research. PMID- 26873011 TI - The small molecule '1-(4-biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate' and its derivatives regulate global protein synthesis by inactivating eukaryotic translation initiation factor 2-alpha. AB - By environmental stresses, cells can initiate a signaling pathway in which eukaryotic translation initiation factor 2-alpha (eIF2-alpha) is involved to regulate the response. Phosphorylation of eIF2-alpha results in the reduction of overall protein neogenesis, which allows cells to conserve resources and to reprogram energy usage for effective stress control. To investigate the role of eIF2-alpha in cell stress responses, we conducted a viability-based compound screen under endoplasmic reticulum (ER) stress condition, and identified 1-(4 biphenylylcarbonyl)-4-(5-bromo-2-methoxybenzyl) piperazine oxalate (AMC-01) and its derivatives as eIF2-alpha-inactivating chemical. Molecular characterization of this signaling pathway revealed that AMC-01 induced inactivation of eIF2-alpha by phosphorylating serine residue 51 in a dose- and time-dependent manner, while the negative control compounds did not affect eIF2-alpha phosphorylation. In contrast with ER stress induction by thapsigargin, phosphorylation of eIF2-alpha persisted for the duration of incubation with AMC-01. By pathway analysis, AMC-01 clearly induced the activation of protein kinase RNA-activated (PKR) kinase and nuclear factor-kappaB (NF-kappaB), whereas it did not modulate the activity of PERK or heme-regulated inhibitor (HRI). Finally, we could detect a lower protein translation rate in cells incubated with AMC-01, establishing AMC-01 as a potent chemical probe that can regulate eIF2-alpha activity. We suggest from these data that AMC-01 and its derivative compounds can be used as chemical probes in future studies of the role of eIF2-alpha in protein synthesis-related cell physiology. PMID- 26873013 TI - Dioxin distribution characteristics and health risk assessment in different size particles of fly ash from MSWIs in China. AB - During the process of treating and recycling Municipal Solid Waste Incinerators (MSWIs) fly ash, polychlorinated dibenzo-p-dioxins (PCDD/Fs) and polychlorinated dibenzofurans (dl-PCBs) in fly ash may potentially mobilize in the atmosphere and be widely distributed in the environment because of the inevitable re-suspension. Thus, this work presents the distributions of PCDD/Fs and dl-PCBs in inhalable coarse particles (Dp10-2.5 (particle diameter in MUm)), fine particles (Dp<2.5) of fly ash and original fly ash from four MSWI plants in China. The results show that PCDD/Fs and dl-PCBs preferentially concentrated in Dp10-2.5 and Dp<2.5. Their mass concentrations and TEQ were significantly higher than those in the original fly ash, but the distribution of PCDD/Fs congeners in Dp10-2.5 and Dp<2.5 was close to that in the original fly ash. The main TEQ contribution included 1,2,3,7,8-PeCDD, 2,3,7,8-TeCDD in PCDDs and 2,3,4,7,8-PeCDF in PCDFs for Dp10-2.5, Dp<2.5 fractions and the original fly ash. Furthermore, the mass and TEQ contribution of dl-PCBs was relatively low. In addition, compared with the fluidized bed, the samples from the grate-type furnaces had significantly lower dioxin concentrations. In terms of potential health risk, the non-carcinogenic risk of PCDD/Fs in Dp10-2.5 and Dp<2.5 were estimated at 9.87 * 10(-1) to 4.81 and 1.19-7.95. For the carcinogenic risk of PCDD/Fs, both accumulation of Hazard Quotients (HQ) in Dp10-2.5 and Dp<2.5 exceeded the threshold limit and should be considered as unacceptable risk for onsite workers. The above findings could provide data to support the risk management of MSWI fly ash during the process of recycle and disposal. PMID- 26873014 TI - High-quality collection and disposal of WEEE: Environmental impacts and resultant issues. AB - Life cycle assessment of the collection, transport and recycling of various types of waste electrical and electronic equipment (WEEE) in Norway shows that small amounts of critical materials (refrigerants, precious/trace metals) are vital for the overall environmental accounts of the value chains. High-quality recycling ensures that materials and energy are effectively recovered from WEEE. This recovery means that responsible waste handling confers net environmental benefits in terms of global warming potential (GWP), for all types of WEEE analysed. For refrigeration equipment, the potential reduction of GWP by high-quality recycling is so large as to be of national significance. For all waste types, the magnitude of the net benefit from recovering materials and energy exceeds the negative consequences of irresponsible disposal. One outcome of this may be widespread misunderstanding of the need for recycling. Furthermore, framing public communication on recycling in terms of avoiding negative consequences, as is essentially universal, may not convey an appropriate message. The issue is particularly important where the consumer regards products as relatively disposable and environmentally benign, and/or where the "null option" of retaining the product at end-of-life is especially prevalent. The paper highlights the implications of all these issues for policy-makers, waste collectors and recyclers, and consumers. PMID- 26873015 TI - Preparation, in vitro degradability, cytotoxicity, and in vivo biocompatibility of porous hydroxyapatite whisker-reinforced poly(L-lactide) biocomposite scaffolds. AB - Biodegradable and bioactive scaffolds with interconnected macroporous structures, suitable biodegradability, adequate mechanical property, and excellent biocompatibility have drawn increasing attention in bone tissue engineering. Hence, in this work, porous hydroxyapatite whisker-reinforced poly(L-lactide) (HA w/PLLA) composite scaffolds with different ratios of HA and PLLA were successfully developed through compression molding and particle leaching. The microstructure, in vitro mineralization, cytocompatibility, hemocompatibility, and in vivo biocompatibility of the porous HA-w/PLLA were investigated for the first time. The SEM results revealed that these HA-w/PLLA scaffolds possessed interconnected pore structures. Compared with porous HA powder-reinforced PLLA (HA-p/PLLA) scaffolds, HA-w/PLLA scaffolds exhibited better mechanical property and in vitro bioactivity, as more formation of bone-like apatite layers were induced on these scaffolds after mineralization in SBF. Importantly, in vitro cytotoxicity displayed that porous HA-w/PLLA scaffold with HA/PLLA ratio of 1:1 (HA-w1/PLLA1) produced no deleterious effect on human mesenchymal stem cells (hMSCs), and cells performed elevated cell proliferation, indicating a good cytocompatibility. Simultaneously, well-behaved hemocompatibility and favorable in vivo biocompatibility determined from acute toxicity test and histological evaluation were also found in the porous HA-w1/PLLA1 scaffold. These findings may provide new prospects for utilizing the porous HA whisker-based biodegradable scaffolds in bone repair, replacement, and augmentation applications. PMID- 26873016 TI - Clinicopathological Features and Long-Term Outcomes of Intraductal Papillary Neoplasms of the Intrahepatic Bile Duct. AB - We intended to investigate the clinicopathological features of intrahepatic intraductal papillary neoplasms of the bile duct (IPNB), especially their malignant features and post-resection prognosis. Forty-three patients who met the definition of IPNB and who underwent liver resection between January 2002 and June 2015 were selected from our institutional database of liver resection cases. The mean age was 63.3 +/- 6.9 years and 24 were male. Hepatolithiasis was present in addition in 10 of the patients. Left- and right-sided hepatectomies and concurrent bile duct resection (BDR) were performed in 28, 15, and 10 patients, respectively; R0 resection was performed in 37 patients. The mean tumor diameter was 4.1 +/- 2.2 cm. Histological tumor grade was low in 4 cases, intermediate in 6, and malignant in 33. There was no cancer-related recurrence or death in the 10 patients with low-grade or intermediate lesions. In the 33 patients with malignant lesions, rates of tumor recurrence and overall survival were 12.5 and 96.2 % at 1 year, 36.4 and 91.3 % at 3 years, and 47.0 and 68.8 % at 5 years, respectively. Multivariate analysis showed that R1 resection was the only prognostic factor for tumor recurrence and patient survival. BDR was performed in only 2 of 6 patients undergoing R1 resection. Intrahepatic IPNB is a rare type of biliary neoplasm that encompasses a histological spectrum ranging from benign disease to invasive malignancy. Long-term survival was anticipated after curative resection. R1 resection reduced survival outcomes; therefore, we suggest that concurrent BDR should be performed if the resection margin of the bile duct is not reliably free of neoplastic involvement. PMID- 26873018 TI - Attentional Set-Shifting Across Species. AB - Attentional set-shifting, as a measure of executive flexibility, has been a staple of investigations into human cognition for over six decades. Mediated by the frontal cortex in mammals, the cognitive processes involved in forming, maintaining and shifting an attentional set are vulnerable to dysfunction arising from a number of human neurodegenerative diseases (such as Alzheimer's, Parkinson's and Huntington's diseases) and other neurological disorders (such as schizophrenia, depression, and attention deficit/hyperactivity disorder). Our understanding of these diseases and disorders, and the cognitive impairments induced by them, continues to advance, in tandem with an increasing number of tools at our disposal. In this chapter, we review and compare commonly used attentional set-shifting tasks (the Wisconsin Card Sorting Task and Intradimensional/Extradimensional tasks) and their applicability across species. In addition to humans, attentional set-shifting has been observed in a number of other animals, with a substantial body of literature describing performance in monkeys and rodents. We consider the task designs used to investigate attentional set-shifting in these species and the methods used to model human diseases and disorders, and ultimately the comparisons and differences between species specific tasks, and between performance across species. PMID- 26873019 TI - Translational Research on Nicotine Dependence. AB - Nicotine dependence is a chronic, relapsing disorder with complex biological mechanisms underlying the motivational basis for this behavior. Although more than 70 % of current smokers express a desire to quit, most relapse within one year, underscoring the need for novel treatments. A key focus of translational research models addressing nicotine dependence has been on cross-validation of human and animal models in order to improve the predictive value of medication screening paradigms. In this chapter, we review several lines of research highlighting the utility of cross-validation models in elucidating the biological underpinnings of nicotine reward and reinforcement, identifying factors which may influence individual response to treatment, and facilitating rapid translation of findings to practice. PMID- 26873020 TI - DNA damage in the oocytes SACs. PMID- 26873021 TI - A comparative analysis of two interferon-gamma releasing assays to detect past tuberculosis infections in Japanese rheumatoid arthritis patients. AB - OBJECTIVES: To compare the utility of QuantiFERON-TB Gold in tube (QFT-GIT) and T SPOT.TB assays to detect past tuberculosis infection in Japanese rheumatoid arthritis patients receiving methotrexate. METHODS: We compared the sensitivities and specificities, the rates of indeterminate results, and the rates of positive results in patients with total and CD4-positive lymphocyte counts of both assays simultaneously performed on 68 rheumatoid arthritis patients receiving methotrexate, in whom 33 had evidence of past tuberculosis infection by chest computed tomography and the other had neither history of tuberculosis exposure nor abnormalities in chest computed tomography. RESULTS: The sensitivities, specificities, and the rates of indeterminate results of QFT-GIT were 21.2%, 100%, and 4.4%, and those of T-SPOT.TB were 21.9%, 100%, and 1.5%, respectively. The overall agreement of both assays was good (kappa = 0.68). In patients with past tuberculosis infection, there are significant positive linear trends in positive rates of both assays across ranges of larger numbers of total and CD4 positive lymphocyte counts. CONCLUSIONS: Both assays were equally useful with high specificities, but may falsely identify past tuberculosis infection owing to low sensitivities. In patients with low total and CD4-positive lymphocyte counts, both assays might give higher rates of false negative results. PMID- 26873017 TI - Translational Assessment of Reward and Motivational Deficits in Psychiatric Disorders. AB - Deficits in reward and motivation are common symptoms characterizing several psychiatric and neurological disorders. Such deficits may include anhedonia, defined as loss of pleasure, as well as impairments in anticipatory pleasure, reward valuation, motivation/effort, and reward learning. This chapter describes recent advances in the development of behavioral tasks used to assess different aspects of reward processing in both humans and non-human animals. While earlier tasks were generally developed independently with limited cross-species correspondence, a newer generation of translational tasks has emerged that are theoretically and procedurally analogous across species and allow parallel testing, data analyses, and interpretation between human and rodent behaviors. Such enhanced conformity between cross-species tasks will facilitate investigation of the neurobiological mechanisms underlying discrete reward and motivated behaviors and is expected to improve our understanding and treatment of neuropsychiatric disorders characterized by reward and motivation deficits. PMID- 26873022 TI - HIV/AIDS stigma among a sample of primarily African-American and Latino men who have sex with men social media users. AB - The recent increase in social media use allows these technologies to rapidly reach communities with higher HIV prevalence, such as African-American and Latino men who have sex with men (MSM). However, no studies have looked at HIV/AIDS stigma among social media users from African-American and Latino MSM communities, or the association between stigma and social media use among these groups. This study sought to assess the level of HIV/AIDS stigma among a sample of social media-using African-American and Latino MSM from Los Angeles. A total of 112 (primarily African-American and Latino, n = 98, 88%) MSM Facebook users completed a survey on demographics, online social network use, and HIV/AIDS stigma. A composite stigma score was created by taking the cumulative score from a 15-item stigma questionnaire. Cumulative logistic models were used to assess the association between HIV/AIDS stigma and online social network use. In general, participants reported a low level of HIV/AIDS stigma (mean = 22.2/75, SD = 5.74). HIV/AIDS stigma composite score was significantly associated with increased time spent on online social networks each day (Adjusted odds ratios (AOR): 1.07, 95% CI: 1.00, 1.15). Among this diverse sample of MSM online social network users, findings suggest that HIV/AIDS stigma is associated with usage of social media. We discuss the implications of this work for future HIV prevention. PMID- 26873024 TI - The Impact of Domestication on the Circadian Clock. AB - A recent publication shows that, during their domestication and spread from Equatorial South America, circadian rhythms of tomatoes have been modified. The modifications have resulted in tomato plants that are adapted to growing under the long day conditions characteristic of summers at higher latitudes. PMID- 26873023 TI - Impact of long-term cropping of glyphosate-resistant transgenic soybean [Glycine max (L.) Merr.] on soil microbiome. AB - The transgenic soybean [Glycine max (L.) Merrill] occupies about 80 % of the global area cropped with this legume, the majority comprising the glyphosate resistant trait (Roundup Ready((r)), GR or RR). However, concerns about possible impacts of transgenic crops on soil microbial communities are often raised. We investigated soil chemical, physical and microbiological properties, and grain yields in long-term field trials involving conventional and nearly isogenic RR transgenic genotypes. The trials were performed at two locations in Brazil, with different edaphoclimatic conditions. Large differences in physical, chemical and classic microbiological parameters (microbial biomass of C and N, basal respiration), as well as in grain production were observed between the sites. Some phyla (Proteobacteria, Actinobacteria, Acidobacteria), classes (Alphaproteobacteria, Actinomycetales, Solibacteres) and orders (Rhizobiales, Burkholderiales, Myxococcales, Pseudomonadales), as well as some functional subsystems (clustering-based subsystems, carbohydrates, amino acids and protein metabolism) were, in general, abundant in all treatments. However, bioindicators related to superior soil fertility and physical properties at Londrina were identified, among them a higher ratio of Proteobacteria:Acidobacteria. Regarding the transgene, the metagenomics showed differences in microbial taxonomic and functional abundances, but lower in magnitude than differences observed between the sites. Besides the site-specific differences, Proteobacteria, Firmicutes and Chlorophyta were higher in the transgenic treatment, as well as sequences related to protein metabolism, cell division and cycle. Although confirming effects of the transgenic trait on soil microbiome, no differences were recorded in grain yields, probably due to the buffering capacity associated with the high taxonomic and functional microbial diversity observed in all treatments. PMID- 26873025 TI - Goal directed hemodynamic therapy based in esophageal Doppler flow parameters: A systematic review, meta-analysis and trial sequential analysis. AB - BACKGROUND: Numerous studies have compared perioperative esophageal doppler monitoring (EDM) guided intravascular volume replacement strategies with conventional clinical volume replacement in surgical patients. The use of the EDM within hemodynamic algorithms is called 'goal directed hemodynamic therapy' (GDHT). METHODS: Meta-analysis of the effects of EDM guided GDHT in adult non cardiac surgery on postoperative complications and mortality using PRISMA methodology. A systematic search was performed in Medline, PubMed, EMBASE, and the Cochrane Library (last update, March 2015). INCLUSION CRITERIA: Randomized clinical trials (RCTs) in which perioperative GDHT was compared to other fluid management. PRIMARY OUTCOMES: Overall complications. SECONDARY OUTCOMES: Mortality; number of patients with complications; cardiac, renal and infectious complications; incidence of ileus. Studies were subjected to quantifiable analysis, pre-defined subgroup analysis (stratified by surgery, type of comparator and risk); pre-defined sensitivity analysis and trial sequential analysis (TSA). RESULTS: Fifty six RCTs were initially identified, 15 fulfilling the inclusion criteria, including 1,368 patients. A significant reduction was observed in overall complications associated with GDHT compared to other fluid therapy (RR=0.75; 95%CI: 0.63-0.89; P=0.0009) in colorectal, urological and high risk surgery compared to conventional fluid therapy. No differences were found in secondary outcomes, neither in other subgroups. The impact on preventing the development of complications in patients using EDM is high, causing a relative risk reduction (RRR) of 50% for a number needed to treat (NNT)=6. CONCLUSIONS: GDHT guided by EDM decreases postoperative complications, especially in patients undergoing colorectal surgery and high-risk surgery. However, no differences versus restrictive fluid therapy and in intermediate-risk patients were found. PMID- 26873026 TI - Severe bilateral papilledema in acute lymphoblastic leukemia. PMID- 26873027 TI - Copper resistance and its regulation in the sulfate-reducing bacterium Desulfosporosinus sp. OT. AB - Desulfosporosinus sp. OT is a Gram-positive, acidophilic sulfate-reducing firmicute isolated from copper tailings sediment in the Norilsk mining-smelting area in Siberia and represents the first Desulfosporosinus species whose genome has been sequenced. Desulfosporosinus sp. OT is exceptionally copper resistant, which made it of interest to study the resistance mechanism. It possesses a copUAZ operon which is shown here to be involved in copper resistance. The copU gene encodes a CsoR-type homotetrameric repressor. By electrophoretic mobility shift assay, it was shown that CopU binds to the operator/promoter region of the copUAZ operon in the absence of copper and is released from the DNA by Cu+ or Ag+, implying that CopU regulates the operon in a copper/silver-dependent manner. DOT_CopA is a P1B-type ATPase related to other characterized, bacterial copper ATPases. When expressed in a copper-sensitive Escherichia coli DeltacopA mutant, it restores copper resistance to WT levels. His-tagged DOT_CopA was expressed from a plasmid in E. coli and purified by Ni-NTA affinity chromatography. The purified enzyme was most active in the presence of Cu(I) and bacterial phospholipids. These findings indicate that the copUAZ operon confers copper resistance to Desulfosporosinus sp. OT, but do not per se explain the basis of the high copper resistance of this strain. PMID- 26873028 TI - Oncologic surveillance in bladder cancer following radical cystectomy: A systematic review and meta-analysis. AB - PURPOSE: The existing guidance on bladder cancer surveillance following radical cystectomy is limited and variable. Additionally, the effect of surveillance on mortality is debatable. Herein, we perform a systematic review to evaluate the characteristics of alternative oncologic surveillance protocols and determine the association of detection of asymptomatic vs. symptomatic recurrences on mortality. METHODS: An electronic search of PubMed, MEDLINE, EMBASE, and Cochrane Library databases was performed from 1970 to 2015. In all, 3 reviewers independently assessed the 1,729 candidate studies for eligibility and abstracted data based on an a priori established protocol. Outcomes were pooled using random effects meta-analysis. RESULTS: We identified 7 studies for inclusion that were uncontrolled and thereby represented a body of evidence at high risk of bias; 5 studies developed surveillance protocols using a methodology similar to that of established guidelines. The majority proposed a pathologic stage-stratified approach, but ended surveillance for all patients at 5 years. Detection of asymptomatic recurrences was associated with a nonsignificant reduction in mortality (relative risk = 0.78; 95% CI: 0.58-1.04). This effect became statistically significant when upper and lower urinary tract recurrences were included in the analyses (relative risk = 0.69; 95% CI: 0.59-0.79). CONCLUSIONS: Only sparse evidence supports alternative oncologic surveillance protocols for bladder cancer following radical cystectomy. The majority of existing protocols proposed similar strategies to those recommended by published guidelines. Detecting asymptomatic recurrences may lead to a reduction in overall mortality, which could provide a rationale for surveillance. PMID- 26873030 TI - Reliable and Efficient Supply Chain Management in Radiology: Implementation of a Two-Bin Demand-Flow System. PMID- 26873029 TI - Let's Use Cognitive Science to Create Collaborative Workstations. AB - When informed by an understanding of cognitive science, radiologists' workstations could become collaborative to improve radiologists' performance and job satisfaction. The authors review relevant literature and present several promising areas of research, including image toggling, eye tracking, cognitive computing, intelligently restricted messaging, work habit tracking, and innovative input devices. The authors call for more research in "perceptual design," a promising field that can complement advances in computer-aided detection. PMID- 26873031 TI - Community Elder Mistreatment Intervention With Capable Older Adults: Toward a Conceptual Practice Model. AB - Community-based elder mistreatment response programs (EMRP), such as adult protective services, that are responsible for directly addressing elder abuse and neglect are under increasing pressure with greater reporting/referrals nationwide. Our knowledge and understanding of effective response interventions represents a major gap in the EM literature. At the center of this gap is a lack of theory or conceptual models to help guide EMRP research and practice. This article develops a conceptual practice model for community-based EMRPs that work directly with cognitively intact EM victims. Anchored by core EMRP values of voluntariness, self-determination, and least restrictive path, the practice model is guided by an overarching postmodern, constructivist, eco-systemic practice paradigm that accepts multiple, individually constructed mistreatment realities and solutions. Harm-reduction, client-centered, and multidisciplinary practice models are described toward a common EMRP goal to reduce the risk of continued mistreatment. Finally, the model focuses on client-practitioner relationship oriented practice skills such as engagement and therapeutic alliance to elicit individual mistreatment realities and client-centered solutions. The practice model helps fill a conceptual gap in the EM intervention literature and carries implications for EMRP training, research, and practice. PMID- 26873032 TI - Mechanisms Linking Neighborhood Age Composition to Health. AB - Purpose of the Study: Age integration theory posits that the age composition of spaces affects the social interactions in which people can engage. This study aimed to examine whether social interactions perceived to involve generativity (i.e., commitment to younger generations), daily discrimination, and/or social cohesion mediate associations between neighborhood age composition, self-reported health, and psychological well-being. Design and Methods: We applied multilevel structural equation models to data from 4,017 participants aged 30-84 who participated in the 2004-2006 wave of National Survey of Midlife Development in the United States, merged with data on their 3,714 neighborhoods from the 2010U.S. Census. Results: Neighborhoods that represented the age distribution of the United States and neighborhoods that overrepresented older adults were contexts in which residents reported the most generativity and social cohesion. In turn, generativity and social cohesion were associated with better self reported health and higher psychological well-being. Implications: The nature of social interaction links neighborhood age composition to health and well-being. These results clarify the results of prior studies, advance measurement, suggest elaborations to age integration theory, and point to new directions for aging-in place initiatives. PMID- 26873033 TI - Adult Children's Responses to Parent "Stubbornness". AB - Purpose of the Study: People cope with relationship tensions in different ways. One such tension that is frequently reported is how adult children respond to conflicts with their aging parents when they see their parents as insisting, resisting, or persisting in their behaviors-acting in ways commonly attributed to stubbornness. Design and Methods: Middle-aged adults (N = 383) completed measures regarding their parents' stubbornness, their responses to that stubbornness, depressive symptoms, positive and negative relationship quality, and support they provide their parents. Multiple regression and multilevel models were utilized to examine whether middle-aged offspring's responses to perceived parent stubbornness were associated with the offspring's reported depressive symptoms, positive and negative relationship quality, and provision of support. Results: Adult children most frequently endorsed responding to parents' "stubborn" behaviors by "just letting their requests go." Results revealed associations of adult children's response strategies with their reports of depressive symptoms (more letting go), positive relationship quality (less letting go and more reasoning), negative relationship quality (more arguing, more rewording their request, and less reasoning), and the amount of support they provide to their parents (more arguing, more reasoning, and more waiting to address the concern another day). Implications: Adult children's responses to perceived parent stubbornness are linked to individual and relationship functioning, as well as the support the children provide. Interventions to develop adaptive responses when there are differences in goals may prove useful for families. PMID- 26873036 TI - Combining angiotensin II receptor 1 antagonism and neprilysin inhibition for the treatment of heart failure. AB - Sacubitril/valsartan is a novel, first-in-class drug, which combines a neprilysin inhibitor with an angiotensin receptor blocker. Sacubitril inhibits neprilysin endopeptidase, blocking the catabolism of natriuretic peptides (NP), thereby increasing their bioavailability. Valsartan counterbalances the increase of angiotensin II that results from neprilysin inhibition, exerting also the beneficial effects of angiotensin receptor blockers seen in previous HF trials. PARADIGM-HF trial has proved the superiority of sacubitril/valsartan (LCZ696) over ACE inhibitor enalapril to reduce mortality and morbidity of symptomatic HF patients with reduced ejection fraction (HFrEF), setting the grounds for the replacement of ACE inhibitors by sacubitril/valsartan in the management of HFrEF. Sacubitril/valsartan is currently being tested in a phase III trial (PARAGON-HF) in patients with HF with preserved EF. PARAGON-HF is also expected to provide further data regarding the long-term safety of sacubitril/valsartan, hopefully to alleviate concerns regarding the effects of neprilysin inhibition on cognitive function. PMID- 26873034 TI - Exploring the relationship between social attachment and dopamine D2/3 receptor availability in the brains of healthy humans using [11C]-(+)-PHNO. AB - Differences in striatal dopamine (DA) function may be related to differences in the degree of social attachment to others. Using positron emission tomography (PET), socially detached persons demonstrate reduced DA D2/3 receptor (D2/3R) availability in the striatum. However, previous PET studies have only used antagonist radiotracers for D2/3R and have not specifically examined regions of interest (ROIs) such as the ventral striatum (VS). In 32 healthy persons, we investigated the relationship between self-reported attachment and DA D2/3R availability in striatal and extrastriatal ROIs as measured using the agonist radiotracer [11C]-(+)-PHNO. Surprisingly, more social attachment-as measured by the attachment subscale of the temperament and character inventory-was related to less [11C]-(+)-PHNO binding in the VS (r(30) = -.43, p = .01). This relationship held in a subsample who also completed the detachment subscale of the Karolinska Scales of Personality (r(10) = .62, p = .03). However, no relationships were observed with BPND in the dorsal striatum or D3R-specific ROIs. One potential explanation for these findings is that persons who are more socially detached have less endogenous DA occupying D2/3R in the VS. This interpretation warrants investigation by future research. These findings may help us better understand the neurochemical basis of attachment. PMID- 26873035 TI - The effect of hydroxychloroquine on lupus erythematosus-like skin lesions in MRL/lpr mice. AB - OBJECTIVES: To evaluate the effect and safety of hydroxychloroquine (HCQ) on lupus erythematosus (LE)-like skin lesions in the MRL/lpr mouse, a model for systemic LE (SLE). METHODS: We divided the MRL/lpr mice into three groups that were given: (1) drinking water, (2) HCQ at a dose of 4 mg/kg/d, or (3) HCQ at a dose of 40 mg/kg/d. The HCQ was administered to examine the effect and safety of HCQ on skin lesions and the number of infiltrating cells including mast cells in the dermis. RESULTS: Six of 13 mice in the group given drinking water, 3 of 11 mice in the group administered low-dose HCQ (4 mg/kg/d), and 1 of 10 mice in the group administered high-dose HCQ (40 mg/kg/d) presented the skin lesions. The average number of mast cells was 81, 50, and 12 (magnification, *100), the mortality rate was 24%, 8%, and 9% and the mean body weight gain was 4.6 g, 8.0 g and 5.1 g, respectively. CONCLUSIONS: HCQ was demonstrated to decrease the appearance of LE-like lesions and the number of mast cells in the dermis. Furthermore, there were no obvious systemic adverse effects. This study provides evidence that suggests benefits in human patients. PMID- 26873037 TI - Oxidative Stress and Histological Alterations of Chicken Brain Induced by Oral Administration of Chromium(III). AB - This experiment was conducted to investigate the oxidative stress in chickens exposed to different concentrations of chromium trichloride (CrCl3) in drinking water. Seventy-two Hylan Brown male chickens were randomly divided into four groups: three experimental groups and one control group. The experimental groups were exposed to three different doses (50 % LD50, 25 % LD50, and 12.5 % LD50) of CrCl3 mg/kg body weight for 42 days, while the control group was given the equivalent water. The activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and non-enzymatic index (glutathione, total antioxidant capacity, malondialdehyde, and hydrogen peroxide) were measured after obtaining the brain samples. Results suggested that 50 % LD50 chromium(III) significantly increased (P < 0.05) the contents of malondialdehyde and hydrogen peroxide. The antioxidant enzyme activities, total glutathione concentration, and total antioxidant capacity decreased significantly (P < 0.05) compared with those of the controls and were consistent with the increase in dosage and time. Additionally, extensive histological alterations were observed in the chicken brain, such as the vacuolization and nuclear condensation of the neurons. These results indicated that exposure to high-dose CrCl3 for a certain time could induce the occurrence of oxidative stress and histological alterations. PMID- 26873039 TI - Gastroretentive systems - a proposed strategy to modulate anthocyanin release and absorption for the management of diabetes. AB - Several reports have indicated a positive correlation between the consumption of anthocyanins (ACN) and biomarkers relating to the improvement of type 2 diabetes (T2D). However, the results from in vitro studies often do not translate into clinical evidence. Potential causes of these discrepancies are experimental conditions that lack physiological relevancy; extensive degradation of these compounds in vivo due to changes in pH and metabolism; and a short residence time in the absorption window in relation to the absorption rate. Here, gastroretentive systems (GRS) are proposed as a strategy to overcome the limitations in ACN delivery and to reduce the existing bench-to-subject gap. This review summarizes recent literature on the use of ACN for the management and control of T2D, followed by GRS platforms to promote a sustained release of ACN for increased health benefits. PMID- 26873040 TI - Uncertainty of trial timing enhances acquisition of conditioned eyeblinks in anxiety vulnerable individuals. AB - Recent work has found that behaviorally inhibited (BI) individuals exhibit enhanced eyeblink conditioning in omission and yoked training as well as with schedules of partial reinforcement. We hypothesized that spacing CS-US paired trials over a longer period of time by extending and varying the inter-trial interval (ITI) would facilitate learning. All participants completed the Adult Measure of Behavioural Inhibition (AMBI) and were grouped as behaviorally inhibited (BI) and non-behaviorally inhibited (NI) based on a median split score of 15.5. All participants received 3 US alone trials and 30CS-US paired trials for acquisition training and 20CS alone trials for extinction training in one session. Conditioning stimuli were a 500 ms tone conditioned stimulus (CS) and a 50-ms air puff unconditional stimulus (US). Participants were randomly assigned to receive a short ITI (mean=30+/- 5s), a long ITI (mean=57+/- 5s) or a variable long ITI (mean=57 s, range 25-123 s). No significant ITI effects were observed for acquisition or extinction. Overall, anxiety vulnerable individuals exhibited enhanced conditioned eyeblink responses as compared to non-vulnerable individuals. This enhanced acquisition of CRs was significant in spaced training with a variable long ITI, but not the short or long ITI. There were no significant effects of ITI or BI on extinction. These findings are interpreted based on the idea that uncertainty plays a role in anxiety and can enhance associative learning in anxiety vulnerable individuals. PMID- 26873038 TI - Hyaluronidase: from clinical applications to molecular and cellular mechanisms. AB - Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical disciplines. The enzyme is considered a "spreading factor" as it decomplexes hyaluronic acid (also called hyaluronan, HA), an essential component of the extracellular matrix (ECM). When applied as an adjuvant, hyaluronidase enhances the diffusion capacity and bioavailability of injected drugs. Therefore, the enzyme has been used as a local adjuvant to increase the diffusion capacity of local anesthetics, increasing the analgesic efficacy, and the anesthetized area particularly in the first minutes following injection, resulting in diminished intra- and postoperative pain. In aesthetic medicine, the off-label use of hyaluronidase is considered the gold standard for the management of HA filler-associated complications. Here, we review the clinical use, underlying biological mechanisms, and future directions for the application of hyaluronidase in surgical and aesthetic medicine. PMID- 26873041 TI - Learning delays in a mouse model of Autism Spectrum Disorder. AB - Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder with core symptoms of atypical social interactions and repetitive behaviors. It has also been reported that individuals with ASD have difficulty with multisensory integration, and this may disrupt higher-order cognitive abilities such as learning and social communication. Impairments in the integration of sensory information could in turn reflect diminished cross-modal white matter connectivity. Moreover, the genetic contribution in ASD appears to be strong, with heritability estimates as high as 90%. However, no single gene has been identified, and over 1000 risk genes have been reported. One of these genes - contactin-associated-like-protein 2 (CNTNAP2) - was first associated with Specific Language Impairment, and more recently has been linked to ASD. CNTNAP2 encodes a cell adhesion protein regulating synaptic signal transmission. To better understand the behavioral and biological underlying mechanisms of ASD, a transgenic mouse model was created with a genetic knockout (KO) of the rodent homolog Cntnap2. Initial studies on this mouse revealed poor social interactions, behavioral perseveration, and reduced vocalizations-all strongly resembling human ASD symptoms. Cntnap2 KO mice also show abnormalities in myelin formation, consistent with a hypo-connectivity model of ASD. The current study was designed to further assess the behavioral phenotype of this mouse model, with a focus on learning and memory. Cntnap2 KO and wild-type mice were tested on a 4/8 radial arm water maze for 14 consecutive days. Error scores (total, working memory, reference memory, initial and repeated reference memory), latency and average turn angle were independently assessed using a 2*14 repeated measures ANOVA. Results showed that Cntnap2 KO mice exhibited significant deficits in working and reference memory during the acquisition period of the task. During the retention period (i.e., after asymptote in errors), Cntnap2 KO mice performed comparably to wild-type mice. These findings suggest that CNTNAP2 may influence the development of neural systems important to learning and cross-modal integration, and that disruption of this function could be associated with delayed learning in ASD. PMID- 26873042 TI - Patient safety: the landscape of the global research output and gender distribution. AB - OBJECTIVES: Patient safety is a crucial issue in medicine. Its main objective is to reduce the number of deaths and health damages that are caused by preventable medical errors. To achieve this, it needs better health systems that make mistakes less likely and their effects less detrimental without blaming health workers for failures. Until now, there is no in-depth scientometric analysis on this issue that encompasses the interval between 1963 and 2014. Therefore, the aim of this study is to sketch a landscape of the past global research output on patient safety including the gender distribution of the medical discipline of patient safety by interpreting scientometric parameters. Additionally, respective future trends are to be outlined. SETTING: The Core Collection of the scientific database Web of Science was searched for publications with the search term 'Patient Safety' as title word that was focused on the corresponding medical discipline. The resulting data set was analysed by using the methodology implemented by the platform NewQIS. To visualise the geographical landscape, state-of-the-art techniques including density-equalising map projections were applied. RESULTS: 4079 articles on patient safety were identified in the period from 1900 to 2014. Most articles were published in North America, the UK and Australia. In regard to the overall number of publications, the USA is the leading country, while the output ratio to the population of Switzerland was found to exhibit the best performance. With regard to the ratio of the number of publications to the Gross Domestic Product (GDP) per Capita, the USA remains the leading nation but countries like India and China with a low GDP and high population numbers are also profiting. CONCLUSIONS: Though the topic is a global matter, the scientific output on patient safety is centred mainly in industrialised countries. PMID- 26873043 TI - Endovascular repair or open repair for ruptured abdominal aortic aneurysm: a Cochrane systematic review. AB - OBJECTIVES: Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA. SETTING: A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included. PARTICIPANTS: 3 RCTs were included, with a total of 761 patients with RAAA. INTERVENTIONS: Meta-analysis was performed with fixed effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was short-term mortality. Secondary outcome measures included aneurysm specific and general complication rates, quality of life and economic analysis. RESULTS: Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions. CONCLUSIONS: Outcomes between eEVAR and open repair, specifically 30 day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions. PMID- 26873044 TI - Can training non-physician clinicians/associate clinicians (NPCs/ACs) in emergency obstetric, neonatal care and clinical leadership make a difference to practice and help towards reductions in maternal and neonatal mortality in rural Tanzania? The ETATMBA project. AB - OBJECTIVES: During late 2010, 36 trainees including 19 assistant medical officers (AMOs) 1 senior clinical officer (CO) and 16 nurse midwives/nurses were recruited from districts across rural Tanzania and invited to join the Enhancing Human Resources and Use of Appropriate Technologies for Maternal and Perinatal Survival in the sub-Saharan Africa (ETATMBA) training programme. The ETATMBA project was training associate clinicians (ACs) as advanced clinical leaders in emergency obstetric care. The trainees returned to health facilities across the country with the hope of being able to apply their new skills and knowledge. The main aim of this study was to explore the impact of the ETATMBA training on health outcomes including maternal and neonatal morbidity and mortality in their facilities. Secondly, to explore the challenges faced in working in these health facilities. DESIGN: The study is a pre-examination/postexamination of maternal and neonatal health indicators and a survey of health facilities in rural Tanzania. The facilities surveyed were those in which ETATMBA trainees were placed post-training. The maternal and neonatal indicators were collected for 2011 and 2013 and the survey of the facilities was in early 2014. RESULTS: 16 of 17 facilities were surveyed. Maternal deaths show a non-significant downward trend over the 2 years (282-232 cases/100,000 live births). There were no significant differences in maternal, neonatal and birth complication variables across the time-points. The survey of facilities revealed shortages in key areas and some are a serious concern. CONCLUSIONS: This study represents a snapshot of rural health facilities providing maternal and neonatal care in Tanzania. Enhancing knowledge, practical skills, and clinical leadership of ACs may have a positive impact on health outcomes. However, any impact may be confounded by the significant challenges in delivering a service in terms of resources. Thus, training may be beneficial, but it requires an infrastructure that supports it. PMID- 26873045 TI - A qualitative process evaluation of training for non-physician clinicians/associate clinicians (NPCs/ACs) in emergency maternal, neonatal care and clinical leadership, impact on clinical services improvements in rural Tanzania: the ETATMBA project. AB - OBJECTIVES: The Enhancing Human Resources and Use of Appropriate Training for Maternal and Perinatal Survival in sub-Saharan Africa (ETATMBA) project is training non-physician clinicians as advanced clinical leaders in emergency maternal and newborn care in Tanzania and Malawi. The main aims of this process evaluation were to explore the implementation of the programme of training in Tanzania, how it was received, how or if the training has been implemented into practice and the challenges faced along the way. DESIGN: Qualitative interviews with trainees, trainers, district officers and others exploring the application of the training into practice. PARTICIPANTS: During late 2010 and 2011, 36 trainees including 19 assistant medical officers one senior clinical officer and 16 nurse midwives/nurses (anaesthesia) were recruited from districts across rural Tanzania and invited to join the ETATMBA training programme. RESULTS: Trainees (n=36) completed the training returning to 17 facilities, two left and one died shortly after training. Of the remaining trainees, 27 were interviewed at their health facility. Training was well received and knowledge and skills were increased. There were a number of challenges faced by trainees, not least that their new skills could not be practised because the facilities they returned to were not upgraded. Nonetheless, there is evidence that the training is having an effect locally on health outcomes, like maternal and neonatal mortality, and the trainees are sharing their new knowledge and skills with others. CONCLUSIONS: The outcome of this evaluation is encouraging but highlights that there are many ongoing challenges relating to infrastructure (including appropriate facilities, electricity and water) and the availability of basic supplies and drugs. This cadre of workers is a dedicated and valuable resource that can make a difference, which with better support could make a greater contribution to healthcare in the country. PMID- 26873046 TI - Which are the most useful scales for predicting repeat self-harm? A systematic review evaluating risk scales using measures of diagnostic accuracy. AB - OBJECTIVES: The aims of this review were to calculate the diagnostic accuracy statistics of risk scales following self-harm and consider which might be the most useful scales in clinical practice. DESIGN: Systematic review. METHODS: We based our search terms on those used in the systematic reviews carried out for the National Institute for Health and Care Excellence self-harm guidelines (2012) and evidence update (2013), and updated the searches through to February 2015 (CINAHL, EMBASE, MEDLINE, and PsychINFO). Methodological quality was assessed and three reviewers extracted data independently. We limited our analysis to cohort studies in adults using the outcome of repeat self-harm or attempted suicide. We calculated diagnostic accuracy statistics including measures of global accuracy. Statistical pooling was not possible due to heterogeneity. RESULTS: The eight papers included in the final analysis varied widely according to methodological quality and the content of scales employed. Overall, sensitivity of scales ranged from 6% (95% CI 5% to 6%) to 97% (CI 95% 94% to 98%). The positive predictive value (PPV) ranged from 5% (95% CI 3% to 9%) to 84% (95% CI 80% to 87%). The diagnostic OR ranged from 1.01 (95% CI 0.434 to 2.5) to 16.3 (95%CI 12.5 to 21.4). Scales with high sensitivity tended to have low PPVs. CONCLUSIONS: It is difficult to be certain which, if any, are the most useful scales for self-harm risk assessment. No scales perform sufficiently well so as to be recommended for routine clinical use. Further robust prospective studies are warranted to evaluate risk scales following an episode of self-harm. Diagnostic accuracy statistics should be considered in relation to the specific service needs, and scales should only be used as an adjunct to assessment. PMID- 26873047 TI - Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project. AB - OBJECTIVE: To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. SETTING/PARTICIPANTS: A linked data set of women aged 20-69 in the Queensland Pap Smear Register (PSR; 1999-2011) and Queensland Cancer Registry (QCR; 1997-2010) formed the Initial Study Cohort. Two extracts (1995-2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20-69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. OUTCOME MEASURES: The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. RESULTS: There were 28,872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76,831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1,372,823 women (PSR n=1,374,401; QCR n=1955), and 5,062,118 records. CONCLUSIONS: Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia. PMID- 26873049 TI - Preventing avoidable incidents leading to a presentation to the emergency department (ED) by older adults with cognitive impairment: protocol for a scoping review. AB - INTRODUCTION: Older adults with cognitive impairment represent a large portion (21-42%) of people (65+) who consult at an emergency department (ED). Because this sub-group is at higher risk for hospitalisation and mortality following an ED visit, awareness about 'avoidable' incidents should be increased in order to prevent presentations to the ED due to such incidents. This study aims to synthetise the actual knowledge related to 'avoidable' incidents (ie, traumatic injuries, poisoning and other consequences of external causes) (WHO, 2016) leading to ED presentations in older people with cognitive impairment. METHODOLOGY AND ANALYSIS: A scoping review will be performed. Scientific and grey literature (1996-2016) will be searched using a combination of key words pertaining to avoidable incidents, ED presentations, older adults and cognitive impairment. A variety of databases (MEDLINE, CINAHL, Ageline, SCOPUS, ProQuest Dissertations/theses, EBM Reviews, Healthstar), online library catalogues, governmental websites and published statistics will be examined. Included sources will pertain to community-dwelling older adults presenting to the ED as a result of an avoidable incident, with the main focus on those with cognitive impairment. Data (eg, type, frequency, severity, circumstances of incidents, preventive measures) will be extracted and analysed using a thematic chart and content analysis. DISCUSSION AND DISSEMINATION: This scoping review will provide a picture of the actual knowledge on the subject and identify knowledge gaps in existing literature to be filled by future primary researches. Findings will help stakeholders to develop programmes in order to promote safe and healthy environments and behaviours aimed at reducing avoidable incidents in seniors, especially those with cognitive impairment. PMID- 26873050 TI - Effect of the rate of chest compression familiarised in previous training on the depth of chest compression during metronome-guided cardiopulmonary resuscitation: a randomised crossover trial. AB - OBJECTIVES: To assess how the quality of metronome-guided cardiopulmonary resuscitation (CPR) was affected by the chest compression rate familiarised by training before the performance and to determine a possible mechanism for any effect shown. DESIGN: Prospective crossover trial of a simulated, one-person, chest-compression-only CPR. SETTING: Participants were recruited from a medical school and two paramedic schools of South Korea. PARTICIPANTS: 42 senior students of a medical school and two paramedic schools were enrolled but five dropped out due to physical restraints. INTERVENTION: Senior medical and paramedic students performed 1 min of metronome-guided CPR with chest compressions only at a speed of 120 compressions/min after training for chest compression with three different rates (100, 120 and 140 compressions/min). Friedman's test was used to compare average compression depths based on the different rates used during training. RESULTS: Average compression depths were significantly different according to the rate used in training (p<0.001). A post hoc analysis showed that average compression depths were significantly different between trials after training at a speed of 100 compressions/min and those at speeds of 120 and 140 compressions/min (both p<0.001). CONCLUSIONS: The depth of chest compression during metronome-guided CPR is affected by the relative difference between the rate of metronome guidance and the chest compression rate practised in previous training. PMID- 26873048 TI - Associations with fracture in patients with diabetes: a nested case-control study. AB - OBJECTIVES: Diabetes mellitus is associated with an increased risk of fractures, which is not fully explained by bone mineral density and common risk factors. The aim of this study is to investigate the association of medication and biochemical markers on the risk of fracture in a diabetes population. DESIGN AND SETTING: A nested case-control study was conducted based on Danish diabetes patients from The Danish National Hospital Discharge Registry. PARTICIPANTS: The cases of the study were diabetes patients with a fracture (n=24,349), and controls were diabetes patients with no fracture (n=132,349). A total of 2627 diabetes patients were available for an analysis of patient characteristics, comorbidities, biochemical parameters and drug usage. RESULTS: Age (OR=1.02, 95% CI 1.01 to 1.04), diabetes duration (OR=1.06, 95% CI 1.02 to 1.09), a diagnosis of previous fracture (OR=2.20, 95% CI 1.55 to 3.11), an alcohol-related diagnosis (OR=2.94, 95% CI 1.76 to 4.91), total cholesterol level (OR=2.50, 95% CI 1.20 to 5.21) and the usage of antiepileptics (OR=2.12, 95% CI 1.39 to 3.59) all increased the odds of fracture. Low-density lipoprotein cholesterol levels decreased the odds of fracture (OR =0.34, 95% CI 0.16 to 0.74), where the level of 3.04-5.96 mmol/L was optimal with regard to fracture risk. CONCLUSIONS: Low-density lipoprotein cholesterol may improve our understanding of fractures in diabetes patients, and it may be added to current fracture risk models in diabetes patients. PMID- 26873051 TI - HPV16 and HPV18 genotyping triage in young women with borderline cytology or mild dyskaryosis: effect of age on genotype-specific risk of high-grade CIN. AB - OBJECTIVE: Human papillomavirus (HPV) triage of borderline cytology or mild dyskaryosis is limited by the higher prevalence of HPV in women with these findings relative to those with high-grade cervical intraepithelial neoplasia (>=CIN2). This is particularly relevant in young women in whom HPV prevalence is discernible. In a previous analysis of HPV triage and colposcopy outcomes in Northern Ireland, we revealed a substantial amount of prevalent high-grade disease in women below 30 years of age. We explored the role of genotyping for HPV16/HPV18 in this population by assessing the risk of high-grade lesions associated with these genotypes and the effect of age on type-specific risk. METHODS: Of the 866 women eligible for HPV triage, those who tested positive for HPV were referred to colposcopy. The relative risk of >=CIN2 for HPV16, HPV18 and non-HPV16/18 high-risk genotype positivity was determined for cobas((r)) HPV Test positive results. RESULTS: The relative risk of high-grade CIN was significantly greater in women infected with HPV16 and/or HPV18 compared with non-HPV16/18 infections, regardless of age (2.23 and 0.45, respectively). In women under 30 years of age, HPV16-associated risk of >=CIN2 was significantly greater than that of HPV18 and the non-HPV16/18 genotypes (1.74 versus 1.03 and 0.58, respectively). In women aged >=30 years, HPV18 infection presented the greatest risk of >=CIN2 (3.03). The relative risk of >=CIN2 associated with non-HPV16/18 genotypes was lower (range, 0.32-0.58) for both age groups. CONCLUSION: This analysis demonstrates the value of genotyping for HPV16/HPV18 and age stratification to improve the specificity of HPV triage and to tailor management relative to the risk of high-grade CIN and cancer. PMID- 26873052 TI - Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules. AB - BACKGROUND: The long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented. METHODS: Measles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations. RESULTS: Of 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV infected children who received two doses of MV at ages 6 and 9 months. Among HIV uninfected children, protective levels of antibody were found post sMV in 90-99% through ages 24-36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV. CONCLUSIONS: Our findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs. PMID- 26873054 TI - Protective and immunological behavior of chimeric yellow fever dengue vaccine. AB - Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. PMID- 26873053 TI - Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation. AB - Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVacTM) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose dependent manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVacTM formulation, a total antigen dose of >= 15 MUg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLPs based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimulatory adjuvant and provide a basis for the development of a GelVacTM bivalent GI/GII.4 norovirus VLP vaccine. PMID- 26873055 TI - Primary and booster vaccination with an inactivated poliovirus vaccine (IPV) is immunogenic and well-tolerated in infants and toddlers in China. AB - INTRODUCTION: Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (PoliorixTM, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China. METHODS: In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study. RESULTS: Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and >= 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in >= 94.7% IPV and >= 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration. CONCLUSION: Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile. PMID- 26873056 TI - Comparison of AS03 and Alum on immune responses elicited by A/H3N2 split influenza vaccine in young, mature and aged BALB/c mice. AB - INTRODUCTION: There is great interest in developing more effective influenza vaccines for the elderly. Oil-in-water adjuvants can boost humoral responses to seasonal vaccines in elderly subjects but relatively little is known about their mechanism of action. METHODS: We compared humoral and cellular immune profiles in young adult (2 months), mature (11-12 months) or aged (16-17 month) female BALB/c mice following two doses of Alum or AS03-adjuvanted A/H3N2 split-virus antigen (A/Uruguay/716/2007) at 0.75 or 3 MUg hemagglutinin (HA) per dose intramuscularly versus 3 MUg HA without adjuvant. RESULTS: Overall, hemagglutination inhibition (HAI), microneutralization (MN) and end-point ELISA titres were higher in the young mice and when an adjuvant was used. Both adjuvants increased humoral responses in older animals but the highest titres across all groups were observed in the AS03-adjuvanted groups. Neither IgG avidity nor A/H3N2-specific splenocyte proliferation was influenced by age, antigen dose or adjuvant. In contrast, cytokine production by ex vivo-stimulated splenocytes differed widely between groups. Most cytokine levels in older mice vaccinated with antigen alone (3 MUg HA/dose) were <= 50% of those in young animals. In young mice, cytokine levels increased modestly with Alum and significantly with AS03. Increases tended to be greatest at the lower antigen dose (0.75 MUg versus 3 MUg HA). In the older animals, Alum had little impact on cytokine production but responses in the AS03 groups paralleled those of the young mice (broad activation of Th1, Th2, and Th17 type cytokines) and the greatest increases were seen with the higher antigen dose (3 MUg HA). CONCLUSIONS: In both young and aged mice, Alum and AS03 increased the magnitude of humoral and cellular responses to split influenza virus vaccination. Overall, these effects were most pronounced in the younger animals and the groups receiving AS03. These data support the use of oil-in-water adjuvants in influenza vaccines targeting the elderly. PMID- 26873058 TI - Academic productivity. PMID- 26873057 TI - A highly conserved epitope-vaccine candidate against varicella-zoster virus induces neutralizing antibodies in mice. AB - Varicella-zoster virus (VZV) is a highly infectious agent of varicella and herpes zoster (HZ). Vaccination is by far the most effective way to prevent these diseases. More safe, stable and efficient vaccines, such as epitope-based vaccines, now have been increasingly investigated by many researchers. However, only a few VZV neutralizing epitopes have been identified to date. We have previously identified a linear epitope between amino acid residues 121 and 135 of gE. In this study, we validated that this epitope is highly conserved amongst different VZV strains that covered five existing phylogenetic clades with an identity of 100%. We evaluated the immunogenicity of the recombinant hepatitis B virus core (HBc) virus-like particles (VLPs) which included amino acids (121 135). VZV-gE-specific antibodies were detected in immunized mouse serum using ELISA. The anti-peptide antiserum positively detected VZV via Western blot and immunofluorescent staining assays. More importantly, these peptides could neutralize VZV, indicating that these peptides represented neutralizing epitopes. These findings have important implications for the development of epitope-based protective VZV vaccines. PMID- 26873059 TI - Identification and characterisation of serine protease inhibitors from Araucaria angustifolia seeds. AB - Araucaria angustifolia seeds are characterised by a relatively high content of starch and protein. This study aimed to verify the presence of alpha-amylase inhibitors in the seeds and to characterise a trypsin inhibitor found in the embryo tissues. Inhibitor purification was carried out by the saline extraction of proteins, acetone precipitation and affinity chromatography. Two protein bands of molecular weight estimated by SDS-PAGE at about 35 kDa were further examined by high-performance liquid chromatography coupled to a mass spectrometer and were shown to be 36.955 Da (AaTI-1) and 35.450 Da (AaTI-2). The sequence of the N terminal region shows that AaTI-1 and AaTI-2 are structurally similar to plant inhibitors of the serpin family. A mixture of AaTI-1 and AaTI-2, identified as AaTI, shows selectivity for the inhibition of trypsin (Kiapp 85 nM) and plasmin (Kiapp 7.0 MUM), but it does not interfere with the chymotrypsin, human plasma kallikrein, porcine kallikrein or other coagulation enzymes activity. PMID- 26873060 TI - Determination of tamoxifen and its metabolites using micelle to solvent stacking in nonaqueous capillary electrophoresis. AB - Micelle to solvent stacking was implemented for the recently established NACE C(4) D method to determine tamoxifen and its metabolites in standard samples and human plasma of breast cancer patients. For stacking, the standard samples and extract after liquid-liquid extraction (LLE) were prepared in methanol and the resulting sample solution was pressure injected after a micellar plug of SDS. Factors that affected the stacking such as SDS concentration, micelle, and sample plug length were examined. The sensitivity enhancement factor (peak height from stacking/peak height from typical injection of sample in BGE) was 15-22. The method detection limits with LLE were in the range of 5-10 ng/mL, which was lower than the established method (where the LLE extract was also prepared in methanol) with reported method detection limits of 25-40 ng/mL. The intraday and interday repeatability were in the range of 1.0-3.4% and 3.8-6.5%, respectively. PMID- 26873061 TI - Global topics and novel approaches in the study of air pollution, climate change and forest ecosystems. AB - Research directions from the 27th conference for Specialists in Air Pollution and Climate Change Effects on Forest Ecosystems (2015) reflect knowledge advancements about (i) Mechanistic bases of tree responses to multiple climate and pollution stressors, in particular the interaction of ozone (O3) with nitrogen (N) deposition and drought; (ii) Linking genetic control with physiological whole tree activity; (iii) Epigenetic responses to climate change and air pollution; (iv) Embedding individual tree performance into the multi-factorial stand-level interaction network; (v) Interactions of biogenic and anthropogenic volatile compounds (molecular, functional and ecological bases); (vi) Estimating the potential for carbon/pollution mitigation and cost effectiveness of urban and peri-urban forests; (vii) Selection of trees adapted to the urban environment; (viii) Trophic, competitive and host/parasite relationships under changing pollution and climate; (ix) Atmosphere-biosphere-pedosphere interactions as affected by anthropospheric changes; (x) Statistical analyses for epidemiological investigations; (xi) Use of monitoring for the validation of models; (xii) Holistic view for linking the climate, carbon, N and O3 modelling; (xiii) Inclusion of multiple environmental stresses (biotic and abiotic) in critical load determinations; (xiv) Ecological impacts of N deposition in the under investigated areas; (xv) Empirical models for mechanistic effects at the local scale; (xvi) Broad-scale N and sulphur deposition input and their effects on forest ecosystem services; (xvii) Measurements of dry deposition of N; (xviii) Assessment of evapotranspiration; (xix) Remote sensing assessment of hydrological parameters; and (xx) Forest management for maximizing water provision and overall forest ecosystem services. Ground-level O3 is still the phytotoxic air pollutant of major concern to forest health. Specific issues about O3 are: (xxi) Developing dose-response relationships and stomatal O3 flux parameterizations for risk assessment, especially, in under-investigated regions; (xxii) Defining biologically based O3 standards for protection thresholds and critical levels; (xxiii) Use of free-air exposure facilities; (xxiv) Assessing O3 impacts on forest ecosystem services. PMID- 26873062 TI - Sphingobacterium griseoflavum sp. nov., isolated from the insect Teleogryllus occipitalis living in deserted cropland. AB - A Gram-stain-negative, aerobic, rod-shaped, non-motile bacterial strain, designated SCU-B140T, was isolated from the insect Teleogryllus occipitalis. Phylogenetic analysis on the basis of 16S rRNA gene sequence showed that strain SCU-B140T belonged to the genus Sphingobacterium. Sphingobacterium bambusae KCTC 22814T (97.87 %) was identified as the most closely related phylogenetic neighbour of strain SCU-B140T. The novel strain was able to grow at salt concentrations of 0-4 % (w/v), at temperatures of 10-40 degrees C, and at a pH of 6.0-9.0. The major cellular fatty acids were iso-C15 : 0, summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1omega7c), C16 : 0, C16 : 0 3-OH, C18 : 0 and C14 : 0. The major polar lipids consisted of phosphatidylethanolamine, three unknown aminophospholipids, an unknown glycolipid and three unknown polar lipids. MK-7 was the major isoprenoid quinone. The DNA G+C content was 41.2 mol%. The DNA-DNA relatedness value between SCU-B140T and S. bambusae KCTC 22814T was found to be 30.15 %. According to these results, strain SCU-B140T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium griseoflavum sp. nov. is proposed. The type strain is SCU-B140T ( = KCTC 42158T = CGMCC 1.12966T). PMID- 26873063 TI - The matching quality of experimental and control interventions in blinded pharmacological randomised clinical trials: a methodological systematic review. AB - BACKGROUND: Blinding is a pivotal method to avoid bias in randomised clinical trials. In blinded drug trials, experimental and control interventions are often designed to be matched, i.e. to appear indistinguishable. It is unknown how often matching procedures are inadequate, so we decided to systematically identify and analyse studies of matching quality in drug trials. Our primary objective was to assess the proportion of studies that concluded that the matching was inadequate; our secondary objective was to describe mechanisms for inadequate matching. METHODS: Systematic review. We searched PubMed, Google Scholar and Web of Science Citation Index for studies that assessed whether supposedly indistinguishable interventions (experimental and control) in randomized clinical drug trials could be distinguished based on physical properties (e.g. appearance or smell). Two persons decided on study eligibility and extracted data independently. Our primary analysis was based on the conclusions of each study. In supportive analyses, we defined a low and a high threshold for inadequate matching. We summarised results qualitatively. RESULTS: We included studies of 36 trials, of which 28 (78%) were published before 1977. The studies differed considerably with regard to design, methodology and analysis. Sixteen of the 36 studies (44%) concluded inadequate matching. When we adapted high or low thresholds for inadequate matching, the number of trials with inadequate matching was reduced to 12 (33%) or increased to 26 (72%). Inadequate matching was concluded in 7 of 22 trials (32%) based on a defined cohort of trials. Inadequate matching was concluded in 9 of 14 trials (64%) which were not based on a trial cohort, and therefore at a higher risk of publication bias. The proportion of inadequate matching did not seem to depend on publication year. Typical mechanisms of inadequate matching were differences in taste or colour. CONCLUSION: We identified matching quality studies of 36 randomized clinical drug trials. Sixteen of the 36 studies (44%) concluded inadequate matching. Few studies of matching quality in contemporary trials have been published, but show similar results as found for older trials. Inadequate matching in drug trials may be more prevalent than commonly believed. PMID- 26873064 TI - Cycloviruses, gemycircularviruses and other novel replication-associated protein encoding circular viruses in Pacific flying fox (Pteropus tonganus) faeces. AB - Viral metagenomic studies have demonstrated that animal faeces can be a good sampling source for exploring viral diversity associated with the host and its environment. As part of an continuing effort to identify novel circular replication-associated protein encoding single-stranded (CRESS) DNA viruses circulating in the Tongan archipelago, coupled with the fact that bats are a reservoir species of a large number of viruses, we used a metagenomic approach to investigate the CRESS DNA virus diversity in Pacific flying fox (Pteropus tonganus) faeces. Faecal matter from four roosting sites located in Ha'avakatolo, Kolovai, Ha'ateiho and Lapaha on Tongatapu Island was collected in April 2014 and January 2015. From these samples we identified five novel cycloviruses representing three putative species, 25 gemycircularviruses representing at least 14 putative species, 17 other CRESS DNA viruses (15 putative species), two circular DNA molecules and a putative novel multi-component virus for which we have identified three cognate molecules. This study demonstrates that there exists a large diversity of CRESS DNA viruses in Pacific flying fox faeces. PMID- 26873065 TI - Diverse circular replication-associated protein encoding viruses circulating in invertebrates within a lake ecosystem. AB - Over the last five years next-generation sequencing has become a cost effective and efficient method for identifying known and unknown microorganisms. Access to this technique has dramatically changed the field of virology, enabling a wide range of environmental viral metagenome studies to be undertaken of organisms and environmental samples from polar to tropical regions. These studies have led to the discovery of hundreds of highly divergent single stranded DNA (ssDNA) virus like sequences encoding replication-associated proteins. Yet, few studies have explored how viruses might be shared in an ecosystem through feeding relationships. Here we identify 169 circular molecules (160 CRESS DNA molecules, nine circular molecules) recovered from a New Zealand freshwater lake, that we have tentatively classified into 51 putatively novel species and five previously described species (DflaCV-3, -5, -6, -8, -10). The CRESS DNA viruses identified in this study were recovered from molluscs (Echyridella menzeisii, Musculium novaezelandiae, Potamopyrgus antipodarum and Physella acuta) and insect larvae (Procordulia grayi, Xanthocnemis zealandica, and Chironomus zealandicus) collected from Lake Sarah, as well as from the lake water and benthic sediments. Extensive diversity was observed across most CRESS DNA molecules recovered. The putative capsid protein of one viral species was found to be most similar to those of members of the Tombusviridae family, thus expanding the number of known RNA-DNA hybrid viruses in nature. We noted a strong association between the CRESS DNA viruses and circular molecules identified in the water and browser organisms (C. zealandicus, P. antipodarum and P. acuta), and between water sediments and undefended prey species (C. zealandicus). However, we were unable to find any significant correlation of viral assemblages to the potential feeding relationships of the host aquatic invertebrates. PMID- 26873068 TI - Editorial. PMID- 26873069 TI - Some Anticancer Agents Act on Human Serum Paraoxonase-1 to Reduce Its Activity. AB - Human serum paraoxonase (hPON1) is an important antioxidant enzyme. It protects low-density lipoproteins against oxidative stress and prevents atherosclerosis development. Anticancer agents have cardiotoxic effects, and this situation can lead to significant complications. Our aim was to evaluate the in vitro effects of some of the anticancer agents such as cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide on the activity of hPON1 in this study. For this reason, PON1 was purified from human serum with a specific activity of 3654.2 EU/mg and 16.84% yield using simple chromatographic methods. The five chemotherapeutic agents dose dependently decreased in vitro hPON1 activity. IC50 values for cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide were 0.0111, 0.042, 0.226, 0.665, and 23.3 mm, respectively. Ki constants were 0.0194, 0.0165, 0.131, 0.291, and 8.973 mm, respectively. The inhibition mechanisms of cetuximab, etoposide, docetaxel, and ifosfamide were non-competitive, and for paclitaxel was competitive. Consequently, inhibition of hPON1 by these anticancer agents may explain some of the cardiotoxic actions of these drugs. PMID- 26873066 TI - Pathophysiology and management of cardiovascular disease in patients with HIV. AB - Results from several studies have suggested that people with HIV have an increased risk of cardiovascular disease, especially coronary heart disease, compared with people not infected with HIV. People living with HIV have an increased prevalence of traditional cardiovascular disease risk factors, and HIV specific mechanisms such as immune activation. Although older, more metabolically harmful antiretroviral regimens probably contributed to the risk of cardiovascular disease, new data suggest that early and continuous use of modern regimens, which might have fewer metabolic effects, minimises the risk of myocardial infarction by maintaining viral suppression and decreasing immune activation. Even with antiretroviral therapy, however, immune activation persists in people with HIV and could contribute to accelerated atherosclerosis, especially of coronary lesions that are susceptible to rupture. Therefore, treatments that safely reduce inflammation in people with HIV could provide additional cardiovascular protection alongside treatment of both traditional and non-traditional risk factors. PMID- 26873070 TI - Usefulness of oocyte accumulation in low ovarian response for PGS. AB - This is an observational study of the response to ovarian stimulation and preimplantational genetic screening (PGS) cycles of 188 patients with a foreseen high aneuploid rate, undergoing two or three stimulation cycles (2SC and 3SC) and oocyte vitrification to accumulate oocytes (Accumulation group = 112 patients) compared to patients undergoing one stimulation cycle (1SC Group= 76 patients) and fresh embryo transfer, between January 2011 and July 2014. Accumulation was performed when <10 MII oocytes were retrieved. Oocytes were vitrified for later warming and IVF, when the planned number of oocytes was achieved. After PGS, euploid embryos were transferred. Comparing 2SC Group with 3SC Group, AMH, AFC, number of oocytes retrieved per pick-up and total number of biopsied embryos were significantly higher in the 2SC Group. After chromosome analysis, 18.5% of biopsied embryos were euploid and 58.9% patients reached embryo transfer. There were no differences in pregnancy rates per patient between the 1SC, 2SC and 3SC Groups (36.8%, 34.9% and 31.0%, respectively) or per embryo transfer (59.6, 56.8 and 60%, respectively). In patients with <10 MII oocytes after ovarian stimulation undergoing PGS, accumulating oocytes can render a pregnancy rate per patient and per embryo transfer comparable to those of fresh PGS cycles. PMID- 26873072 TI - Comparison of a lateral flow milk progesterone test with enzyme immunoassay as an aid for reproductive status determination in cows. AB - The lateral flow test (LFT) is an immunochromatographic method that utilises an immunostrip for non-laboratory diagnostic purposes. The present study evaluated a milk progesterone LFT against the enzyme immunoassay (EIA) to confirm oestrus and a non-pregnancy diagnosis. In total, 277 milk samples from 70 cows were analysed, collected on the day of artificial insemination and at 19 days, 21 days and 24 days post insemination. The level of accuracy of the LFT compared with the EIA was 95.0 per cent for milk samples containing <2 ng/ml progesterone and 97.0 per cent for milk samples containing >10 ng/ml progesterone. The validation of oestrus by the LFT was 98.6 per cent accurate using 2 ng/ml progesterone as the EIA estimate for oestrus. The test performance for a non-pregnancy diagnosis was subject to the day of milk sampling, showing the highest accuracy on day 24 post insemination for both tests. When optimised for maximum specificity, and compared with rectal palpation, the LFT had a sensitivity and specificity for non pregnancy diagnosis on day 24 post insemination of 75.0 per cent and 100.0 per cent, respectively, with an overall accuracy of 84.4 per cent. The corresponding characteristics for the quantitative EIA were 85.0 per cent, 100.0 per cent and 90.6 per cent, respectively. The LFT results compared favourably with the quantitative milk progesterone EIA. PMID- 26873074 TI - Editorial: Polymeric Nanomedicines for Malignancy Therapy. PMID- 26873071 TI - Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications. AB - Although plant expression systems used for production of therapeutic proteins have the advantage of being scalable at a low price, the downstream processing necessary to obtain pure therapeutic molecules is as expensive as for the traditional Chinese hamster ovary (CHO) platforms. However, when edible plant tissues (EPTs) are used, there is no need for exhaustive purification, because they can be delivered orally as partially purified formulations that are safe for consumption. This economic benefit is especially interesting when high doses of recombinant proteins are required throughout the treatment/prophylaxis period, as is the case for antibodies used for oral passive immunization (OPI). The secretory IgA (SIgA) antibodies, which are highly abundant in the digestive tract and mucosal secretions, and thus the first choice for OPI, have only been successfully produced in plant expression systems. Here, we cover most of the up to-date examples of EPT-produced pharmaceuticals, including two examples of SIgA aimed at oral delivery. We describe the benefits and drawbacks of delivering partially purified formulations and discuss a number of practical considerations and criteria to take into account when using plant expression systems, such as subcellular targeting, protein degradation, glycosylation patterns and downstream strategies, all crucial for improved yield, high quality and low cost of the final product. PMID- 26873073 TI - LInking EDCs in maternal Nutrition to Child health (LINC study) - protocol for prospective cohort to study early life exposure to environmental chemicals and child health. AB - BACKGROUND: The presence of chemicals in the environment is ubiquitous. Human biomonitoring studies have shown that various chemicals can be detected in the majority of the population, including pregnant women. These compounds may pass the placenta, and reach the fetus. This early life exposure in particular may be detrimental as some chemicals may disrupt the endocrine system, which is involved in various processes during development. The LINC study is a prospective birth cohort designed to study associations between early life environmental exposures and child health, including growth and neurodevelopment. The purpose of this paper is to give an overview of this cohort. METHODS AND DESIGN: Recruitment for this cohort has started in 2011 in three Dutch areas and is still ongoing. To date over 300 mother-child pairs have been included. Women are preferably included during the first trimester of pregnancy. Major congenital anomalies and twin births are reasons for exclusion. To assess exposure to environmental chemicals, cord blood, placenta, meconium and vernix are collected. Parents collect urine of the child shortly after birth and breast milk in the second month of life. Exposure to a broad range of environmental chemicals are determined in cord plasma and breast milk. Furthermore various hormones, including leptin and cortisone, are determined in cord plasma, and in heel prick blood spots (thyroxine). Data on anthropometry of the child is collected through midwives and youth health care centres on various time points until the child is 18 months of age. Furthermore cognitive development is monitored by means of the van Wiechen scheme, and information on behavioral development is collected by means of the infant behavior questionnaire and the child behavior checklist. When the child is 12 months of age, a house visit is scheduled to assess various housing characteristics, as well as hand-to-mouth behavior of the child. At this visit exposure of the child to flame retardants (with endocrine disrupting properties) in house dust is determined by means of body wipes. They are furthermore also measured in a saliva sample of the child. Next to these measurements, women receive questionnaires each trimester regarding amongst others lifestyle of the parents, general health of the parents and the child, and mental state of the mother. DISCUSSION: This study was approved by the medical ethics committee of the VU University Medical Centre. Consent for the infant is given by the mother, who is specifically required to give consent for both herself as well as her child. Results will be published regardless of the findings of this study, and will be widely disseminated among related medical stakeholders (e.g. midwives and pediatricians), policy makers, and the general public. PMID- 26873076 TI - Acidity-Activated Shielding Strategies of Cationic Gene Delivery for Cancer Therapy. AB - Cationic gene vectors increased attractive for gene therapy. However, unstable systemic circulation due to the interaction of gene delivery system with blood cells limited the further application. Therefore, pH sensitive shielding systems were exploited, by which, the positive surface charge density of polyplexes was reduced, circulation time was improved and pH-triggered targeting delivery was promised. This mini review mainly focuses on the development of solid tumors pH environment activated shielding systems for cationic gene vectors. This shielding strategy shows great potential for enhancing efficient gene transporting and achieving better therapeutic effects in acidic tumor treatment. PMID- 26873077 TI - Salvianolic Acid A Attenuates Cell Apoptosis, Oxidative Stress, Akt and NF-kappaB Activation in Angiotensin-II Induced Murine Peritoneal Macrophages. AB - We discuss the role of Salvianolic acid A(SAA), one of the main effective components in Salvia Miltiorrhiza (known as 'Danshen' in traditional Chinese medicine), in apoptotic factors, the production of oxidative products, and the expression of Akt and NF-kappaB in angiotensin II (Ang II)-mediated murine macrophages. In the present study, Ang II was added to mice abdominal macrophages with or without addition of SAA. After cell identification, apoptosis was measured by DNA strand break level with TdT-mediated dUTP nick-end labeling (TUNEL) staining, and the expression of Bcl-2 and Bax. Intracellular concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Western blotting determined the expression of Akt, p-Akt, NF-kappaB and p-NF-kappaB. Ly294002 (the inhibitor of PI3K) was used to determine the mechanism of SAA. Ang II (1 uM) significantly increased the number of TUNEL-positive cells and Bax expression, but reduced Bcl-2 expression. These effects were antagonized when the cells were pretreated with SAA. SAA decreased MDA, but increased SOD in the cell lysis solution treated with Ang II. It markedly reduced the level of p NF-kappaB, as also p-Akt, which was partly blocked by Ly294002. SAA prevents Ang IIinduced apoptosis, oxidative stress and related protein expression in the macrophages. It also inhibits the activation of Akt. PMID- 26873078 TI - Estimation of Antifungal Activity of Mevastatin Produced by Aspergillus terreus GCBL-03 on pretreated substrate in solid state fermentation. AB - This project was planned to study the production of cholesterol lowering drug mevastatin by Aspergillus terreus GCBL-03 on pretreated substrate bagasse in solid state fermentation. Bagasse was pretreated by potassium hydroxide to delignify the substrate to readily become available to microorganism. It was noticed that pretreated bagasse exhibited 13.69+/-0.64 mg/100mL yield of mevastatin and 6.63+/-0.48 g dry cell mass as compared to nontreated substrate that showed 7.04+/-0.81 mg/100 mL and 6.04+/-0.24 g dry cell mass. The fermentation profile like pH (5.5), temperature (30 degrees C), moisture contents (60%) inoculum size (2 mL), and incubation time (72 h) showed the optimum production (30.63+/-1.24 mg/100 mL) of mevastatin. Furthermore, fermented drug showed noteworthy antifungal activity against battery of selected fungal strains assessed by disc diffusion and measurement of minimum inhibitory concentration by micro dilution method. It was concluded from the study that fermented mevastatin was effective against fungal strains. PMID- 26873075 TI - Biodegradable Stimuli-Responsive Polymeric Micelles for Treatment of Malignancy. AB - In the past decade, drug delivery systems that can respond to the tumor microenvironment or external stimuli have emerged as promising platforms for treating malignancies due to their improved antitumor efficacy and reduced side effects. In particular, biodegradable polymeric micelles have attracted increasing attention and been rapidly developed as a distinct therapeutic to overcome limitations of conventional chemotherapeutic anticancer drugs. Because of their advantages with respect to biocompatibility, degradability, circulation time, and tumor accumulation, considerable effort has been dedicated to the developing and optimizing micellar systems during the past few years. This review highlights recent advances concerning stimuli-responsive micelles made of biodegradable polypeptide and polyester as nanocarries for drug delivery, and especially limits the content to pH sensitive, redox sensitive, and photo sensitive micellar systems for safe and efficient cancer chemotherapy. PMID- 26873079 TI - Chemerin in peritoneal sepsis and its associations with glucose metabolism and prognosis: a translational cross-sectional study. AB - BACKGROUND: Stress hyperglycaemia (SHG) is a common complication in sepsis associated with poor outcome. Chemerin is an adipocytokine associated with inflammation and impaired glucose homeostasis in metabolic diseases such as type 2 diabetes (T2D). We aimed to investigate how alterations of circulating chemerin levels and corresponding visceral adipose tissue (VAT) expression are linked to glucose metabolism and prognosis in sepsis. METHODS: Clinical data and tissue samples were taken from a cross-sectional study including control, T2D and sepsis patients, all undergoing laparotomy. A second independent patient cohort of patients with sepsis was included to evaluate associations with prognosis. This was complemented by a murine model of peritoneal infection and a high-fat diet. We analysed circulating chemerin by enzyme-linked immunosorbent assay and VAT messenger RNA (mRNA) expression by real-time polymerase chain reaction. RESULTS: Circulating chemerin was increased in sepsis 1.69-fold compared with controls (p = 0.012) and 1.47-fold compared with T2D (p = 0.03). Otherwise, chemerin VAT mRNA expression was decreased in patients with sepsis (p = 0.006) and in septic diabetic animals (p = 0.009). Circulating chemerin correlated significantly with intra-operative glucose (r = 0.662; p = 0.01) and in trend with fasting glucose (r = 0.528; p = 0.052). After adjusting for body mass index or haemoglobin A1c, chemerin correlated in trend with insulin resistance evaluated using the logarithmised homeostasis model assessment of insulin resistance (r = 0.539, p = 0.071; r = 0.553, p = 0.062). Chemerin was positively associated with Acute Physiology and Chronic Health Evaluation II score in patients with sepsis (p = 0.036) and with clinical severity in septic mice (p = 0.031). In an independent study population, we confirmed association of chemerin with glucose levels in multivariate linear regression analysis (beta = 0.556, p = 0.013). In patients with sepsis with SHG, non-survivors had significantly lower chemerin levels than survivors (0.38-fold, p = 0.006), while in patients without SHG, non-survivors had higher chemerin levels, not reaching significance (1.64-fold, p = 0.089). No difference was apparent in patients with pre-existing T2D (p = 0.44). CONCLUSIONS: We show, for the first time to our knowledge, that chemerin is increased in sepsis and that it associates with impaired glucose metabolism and survival in these patients. It could be further evaluated as a biomarker to stratify mortality risk of patients with SHG. PMID- 26873081 TI - Involvement of M1 and CB1 receptors in the anxiogenic-like effects induced by neostigmine injected into the rat prelimbic medial prefrontal cortex. AB - The prelimbic (PL) medial prefrontal cortex is a brain region highly involved in the control of emotional responses, being modulated by several neurotransmitter systems, including the cholinergic and endocannabinoid. Activation of muscarinic type 1 (M1) receptors in the brain induces retrograde suppression of inhibition through the induction of endocannabinoid release, which, in turn, activates cannabinoid type 1 (CB1) receptors. No study so far, however, has been conducted to investigate if the cholinergic and endocannabinoid systems interact in the PL to modulate anxiety-related behaviors. Thus, the present work aimed at verifying if intra-PL administration of neostigmine, an acetylcholinesterase inhibitor, would produce changes in anxiety-like behavior and if these effects are mediated by M1 and CB1 receptor activation. Independent groups of animals received bilateral injections of vehicle, the M1 receptor antagonist pirenzepine (0.06, 0.6, and 6 nmol), the CB1 receptor antagonist AM251 (0.1 nmol), or the fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597 (1, 3, and 10 pmol), followed by vehicle or neostigmine (0.01, 0.1, and 1 nmol), and were submitted to the elevated plus-maze (EPM) test. Neostigmine (1 nmol) decreased open arm exploration of the maze. This anxiogenic-like effect was reproduced in another anxiety-related animal model, the light-dark box. Previous injection of pirenzepine or AM251 abolished this response in the EPM, whereas URB597 had no effect. These results suggest that CB1 and M1 receptors interact in the PL to control anxiety-like behaviors. PMID- 26873080 TI - Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways. AB - RATIONALE AND OBJECTIVES: Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models are also helping to decipher the neurobiological substrates of associated neuropsychiatric complications. This review summarizes our work on the influence of METH self-administration on dopamine systems, transcription and immune responses in the brain. METHODS: We used the rat model of METH self administration with extended access (15 h/day for eight consecutive days) to investigate the effects of voluntary METH intake on the markers of dopamine system integrity and changes in gene expression observed in the brain at 2 h-1 month after cessation of drug exposure. RESULTS: Extended access to METH self administration caused changes in the rat brain that are consistent with clinical findings reported in neuroimaging and postmortem studies of human METH addicts. In addition, gene expression studies using striatal tissues from METH self administering rats revealed increased expression of genes involved in cAMP response element binding protein (CREB) signaling pathway and in the activation of neuroinflammatory response in the brain. CONCLUSION: These data show an association of METH exposure with activation of neuroplastic and neuroinflammatory cascades in the brain. The neuroplastic changes may be involved in promoting METH addiction. Neuroinflammatory processes in the striatum may underlie cognitive deficits, depression, and parkinsonism reported in METH addicts. Therapeutic approaches that include suppression of neuroinflammation may be beneficial to addicted patients. PMID- 26873082 TI - A role for the endocannabinoid 2-arachidonoyl-sn-glycerol for social and high-fat food reward in male mice. AB - RATIONALE: The endocannabinoid system is an important modulator of brain reward signaling. Investigations have focused on cannabinoid (CB1) receptors, because dissection of specific contributions of individual endocannabinoids has been limited by the available toolset. While we recently described an important role for the endocannabinoid anandamide in the regulation of social reward, it remains to be determined whether the other major endocannabinoid, 2-arachidonoyl-sn glycerol (2-AG), serves a similar or different function. OBJECTIVES: To study the role of 2-AG in natural reward, we used a transgenic mouse model (MGL-Tg mice) in which forebrain 2-AG levels are selectively reduced. We complemented behavioral analysis with measurements of brain 2-AG levels. METHODS: We tested male MGL-Tg mice in conditioned place preference (CPP) tasks for high-fat food, social contact, and cocaine. We measured 2-AG content in the brain regions of interest by liquid chromatography/mass spectrometry. RESULTS: Male MGL-Tg mice are impaired in developing CPP for high-fat food and social interaction, but do develop CPP for cocaine. Furthermore, compared to isolated mice, levels of 2-AG in socially stimulated wild-type mice are higher in the nucleus accumbens and ventral hippocampus (183 and 140 % of controls, respectively), but unchanged in the medial prefrontal cortex. CONCLUSIONS: The results suggest that reducing 2-AG mediated endocannabinoid signaling impairs social and high-fat food reward in male mice, and that social stimulation mobilizes 2-AG in key brain regions implicated in the control of motivated behavior. The time course of this response differentiates 2-AG from anandamide, whose role in mediating social reward was previously documented. PMID- 26873083 TI - Attenuation of nicotine-taking and nicotine-seeking behavior by the mGlu2 receptor positive allosteric modulators AZD8418 and AZD8529 in rats. AB - RATIONALE: Numerous medication development strategies seek to decrease nicotine consumption and prevent relapse to tobacco smoking by blocking glutamate transmission. Decreasing glutamate release by activating presynaptic inhibitory metabotropic glutamate (mGlu)2/3 receptors inhibits the reinforcing effects of nicotine and blocks cue-induced reinstatement of nicotine-seeking behavior in rats. However, the relative contribution of mGlu2 receptors in nicotine dependence is still unknown. OBJECTIVES: The present study evaluated the role of mGlu2 receptors in nicotine-taking and nicotine-seeking behavior using the novel, relatively selective mGlu2 positive allosteric modulators (PAMs) AZD8418 and AZD8529. RESULTS: Acute treatment with AZD8418 (0.37, 1.12, 3.73, 7.46, and 14.92 mg/kg) and AZD8529 (1.75, 5.83, 17.5, and 58.3 mg/kg) deceased nicotine self administration and had no effect on food-maintained responding. Chronic treatment with AZD8418 attenuated nicotine self-administration, but tolerance to this effect developed quickly. The inhibition of nicotine self-administration by chronic AZD8529 administration persisted throughout the 14 days of treatment. Chronic treatment with either PAMs inhibited food self-administration. AZD8418 (acute) and AZD8529 (acute and subchronic) blocked cue-induced reinstatement of nicotine- and food-seeking behavior. CONCLUSIONS: These findings indicate an important role for mGlu2 receptors in the reinforcing properties of self administered nicotine and the motivational impact of cues that were previously associated with nicotine administration (i.e., cue-induced reinstatement of nicotine-seeking behavior). Thus, mGlu2 PAMs may be useful medications to assist people to quit tobacco smoking and prevent relapse. PMID- 26873084 TI - Incidental findings of uncertain significance: To know or not to know--that is not the question. AB - BACKGROUND: Although the "right not to know" is well established in international regulations, it has been heavily debated. Ubiquitous results from extended exome and genome analysis have challenged the right not to know. American College of Medical Genetics and Genomics (ACMG) Recommendations urge to inform about incidental findings that pretend to be accurate and actionable. However, ample clinical cases raise the question whether these criteria are met. Many incidental findings are of uncertain significance (IFUS). The eager to feedback information appears to enter the field of IFUS and thereby threaten the right not to know. This makes it imperative to investigate the arguments for and against a right not to know for IFUS. DISCUSSION: This article investigates how the various arguments for and against a right not to know hold for IFUS. The main investigated arguments are: hypothetical utilitarianism, the right-based argument, the feasibility argument, the value of knowledge argument, the argument from lost significance, the empirical argument, the duty to disclose argument, the avoiding harm argument; the argument from principle, from autonomy, from privacy, as well as the argument from the right to an open future. The analysis shows that both sides in the debate have exaggerated the importance of incidental findings. Opponents of a right not to know have exaggerated the importance of IFUS, while proponents have exaggerated the need to be protected from something that is not knowledge. Hence, to know or not to know is not the question. The question is whether we should be able to stay ignorant of incidental findings of uncertain significance, if we want to. The answer is yes: As long as the information is not accurate and/or actionable: ignorance is bliss. When answering questions that are not asked, we need to think twice. PMID- 26873086 TI - Food allergy and eosinophilic esophagitis in India: Lack of diagnosis. PMID- 26873085 TI - Non-HFE iron overload as a surrogate marker of disease severity in patients of liver cirrhosis. AB - BACKGROUND: Decompensated liver cirrhosis is an important cause of mortality worldwide. Various modifiable and non-modifiable factors are involved in the pathogenesis of cirrhosis and its complications. This study was aimed to evaluate the association of iron overload and disease severity in patients of liver cirrhosis and its association with HFE gene mutation. METHODS: Forty-nine patients with decompensated liver cirrhosis were recruited. Clinical and laboratory parameters were compared in patients with and without iron overload. C282Y and H63D gene mutation analysis was performed in all patients with iron overload. RESULTS: Iron overload was found in 20 (40.82%) patients. A significant positive correlation of transferrin saturation with Child-Turcotte-Pugh (CTP) score (r = 0.705, p < 0.001) and model for end-stage liver disease (MELD) score (r = 0.668, p < 0.001) was found. Transferrin saturation was also independently associated with high CTP and MELD score on multivariate analysis. Mortality over 3 months was significantly more common in iron-overloaded patients (p = 0.028). C282Y homozygosity or C282Y/H63D compound heterozygosity was not found in any of the patients with iron overload. CONCLUSION: Iron overload was significantly associated with disease severity and reduced survival in patients of decompensated liver cirrhosis. PMID- 26873088 TI - Paracetamol exposure prenatally and in infancy is linked to asthma, study shows. PMID- 26873087 TI - Endoscopic management of post-liver transplant billiary complications: A prospective study from tertiary centre in India. AB - BACKGROUND: Liver transplantation has become common in India over the last decade and biliary strictures after the procedure cause a significant morbidity. Endoscopic retrograde cholangiopancreatography (ERCP) is a safe and effective treatment modality for post-transplant biliary strictures so we decided to evaluate prospectively the outcomes of endoscopic treatment in post-living donor liver transplantation (LDLT) biliary strictures. METHODS: We studied ten consecutive patients who had developed biliary strictures (out of 312 who had undergone liver transplantation between June 2009 and June 2013) and had been referred to the Department of Gastroenterology for management. All patients underwent liver function tests, ultrasound of the abdomen, magnetic resonance cholangiography and liver biopsy, if this was indicated. RESULTS: Of these 312 patients who underwent liver transplantation, 305 had living donors (LDLT) and 7 deceased donors (DDLT). Ten patients in the LDLT group (3.3%) developed biliary strictures. There were seven males and three females who had median age of 52 years (range 4-60 years). The biliary anastomosis was duct-to-duct in all patients with one patient having an additional duct-to-jejunum anastomosis. The mode of presentation was cholangitis in four patients (40%), asymptomatic elevation of liver enzymes in four (40%) and jaundice in two patients (20%). The median time from transplantation to the detection of the stricture was 12 months (2-42.5 months). ERCP was attempted as initial therapy in all patients: seven were managed entirely by endoscopic therapy, and three required a combined percutaneous and endoscopic approach. Cholangiography demonstrated anastomotic stricture in all patients. A total of 32 sessions of ERCP were done with mean of 3.2 (2-5) endoscopic sessions and 3.4 (1-6) stents required to resolve the stricture. The median time from the first intervention to stricture resolution was 4 months (range 2-12 months). In four patients, the stents were removed after one session and in two patients each after two, three and four sessions. In six patients more than one stent was placed and all of them required dilatation of stricture. Seven patients completed treatment and are off stents at a median follow up period of 9.5 months (7-11 months). Two patients developed recurrence of their stricture after 7.5 months. Both had long strictures and required a combined endoscopic and percutaneous approach. There was one mortality due to sepsis secondary to cholangitis. CONCLUSIONS: Post-LDLT biliary strictures can be successfully treated with ERCP, and most patients remain well on follow up (median 9.5 months). A combined endoscopic and percutaneous approach is useful when ERCP alone fails. PMID- 26873089 TI - Relapsed and refractory subcutaneous panniculitis-like T-cell lymphoma with excellent response to cyclosporine: a case report and literature review. PMID- 26873090 TI - The Role of Physician Recommendations and Public Policy in Human Papillomavirus Vaccinations. AB - BACKGROUND: Immunization rates for human papillomavirus (HPV) infections remain low among teenagers despite strong evidence of the effectiveness of vaccines. Physician recommendations of the vaccine are far from universal. Several states have enacted policies that mandate HPV vaccination or distribute educational materials. OBJECTIVES: To provide policy makers, physicians, and researchers information on the relative importance of physician recommendations and early state-level policies to promote HPV vaccinations among targeted age groups. METHODS: We first use probit models to determine the strongest correlates of immunization in a nationally representative US sample of teenagers. We then use instrumental variable probit models to determine the direct role that physician recommendations play in vaccination using plausibly exogenous physician encounters that are likely not the result of more health-conscious parents seeking out information on the vaccine. RESULTS: We show that children in the targeted age range who are more likely to encounter physicians for reasons other than seeking out the vaccine, such as through mandatory wellness exams or previous asthma diagnoses, are significantly more likely to get the vaccine. There is no consistent evidence that the state policies we analyze have been effective. CONCLUSION: Encouraging recommendations by physicians may be the most effective path toward increasing HPV vaccination. State-level mandates and policies are yet to exhibit effectiveness. PMID- 26873091 TI - Cost-Effectiveness Analyses of Lung Cancer Screening Strategies Using Low-Dose Computed Tomography: a Systematic Review. AB - BACKGROUND: Lung cancer screening with low-dose computed tomography (LDCT) has been shown to deliver appreciable reductions in mortality in high-risk patients. However, in an era of constrained medical resources, the cost-effectiveness of such a program needs to be demonstrated. OBJECTIVE: The aim of this study was to systematically review the literature analyzing the cost-effectiveness of lung cancer screening using LDCT. METHODS: We searched MEDLINE, EMBASE, EBM Reviews Health Technology Assessment, the National Health Service Economic Evaluation Database (NHS-EED), and the Cochrane Database of Systematic Reviews. Due to technological progress in CT, we limited our search to studies published between January 2000 and December 2014. Our search returned 393 unique results. After removing studies that did not meet our inclusion criteria, 13 studies remained. Costs are presented in 2014 US dollars (US$). RESULTS: The results from the economic evaluations identified in this review were varied. All identified studies reported outcomes using either additional survival (life-years gained) or quality-adjusted life-years (QALYs gained). Results ranged from US$18,452 to US$66,480 per LYG and US$27,756 to US$243,077 per QALY gained for repeated screening. The results of cost-effectiveness analyses were sensitive to several key model parameters, including the prevalence of lung cancer, cost of LDCT for screening, the proportion of lung cancer detected as localized disease, lead time bias, and, if included, the characteristics of a smoking cessation program. CONCLUSIONS: The cost-effectiveness of a lung cancer screening program using LDCT remains to be conclusively resolved. It is expected that its cost-effectiveness will largely depend on identifying an appropriate group of high-risk subjects. PMID- 26873092 TI - Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. AB - Aims: Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches. Methods and results: Using the approaches of molecular and cellular biology, we show that a circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence. Doxorubicin induced cardiomyopathy was aggravated by ectopic expression of circ-Foxo3 but was relieved by silencing endogenous circ-Foxo3. We also found that silencing circ Foxo3 inhibited senescence of mouse embryonic fibroblasts and that ectopic expression of circ-Foxo3 induced senescence. We found that circ-Foxo3 was mainly distributed in the cytoplasm, where it interacted with the anti-senescent protein ID-1 and the transcription factor E2F1, as well as the anti-stress proteins FAK and HIF1alpha. Conclusion: We conclude that ID-1, E2F1, FAK, and HIF1alpha interact with circ-Foxo3 and are retained in the cytoplasm and could no longer exert their anti-senescent and anti-stress roles, resulting in increased cellular senescence. PMID- 26873093 TI - Mobile technology and the digitization of healthcare. AB - The convergence of science and technology in our dynamic digital era has resulted in the development of innovative digital health devices that allow easy and accurate characterization in health and disease. Technological advancements and the miniaturization of diagnostic instruments to modern smartphone-connected and mobile health (mHealth) devices such as the iECG, handheld ultrasound, and lab-on a-chip technologies have led to increasing enthusiasm for patient care with promises to decrease healthcare costs and to improve outcomes. This 'hype' for mHealth has recently intersected with the 'real world' and is providing important insights into how patients and practitioners are utilizing digital health technologies. It is also raising important questions regarding the evidence supporting widespread device use. In this state-of-the-art review, we assess the current literature of mHealth and aim to provide a framework for the advances in mHealth by understanding the various device, patient, and clinical factors as they relate to digital health from device designs and patient engagement, to clinical workflow and device regulation. We also outline new strategies for generation and analysis of mHealth data at the individual and population-based levels. PMID- 26873094 TI - Fat: an emerging player in the field of atrial fibrillation. PMID- 26873095 TI - Implantable cardioverter-defibrillators in adults with congenital heart disease: a systematic review and meta-analysis. AB - AIMS: Sudden cardiac death is a major cause of mortality in adult congenital heart disease (ACHD) patients. The indications for implantable cardioverter defibrillator (ICD) implantation in ACHD patients are still not well established. We aim to systematically review the literature on indications and outcome of ICD implantation in ACHD patients. METHODS AND RESULTS: We performed a comprehensive search in EMBASE, MEDLINE, and Google Scholar to identify all studies on ICD implantation in ACHD patients. We used random effects models to calculate proportions and 95% confidence intervals. Of 1356 articles, 24 studies with 2162 patients were included, with a mean follow-up of 3.6 +/- 0.9 years. Half of patients had tetralogy of Fallot. Mean age at implantation was 36.5 +/- 5.5 years old and 66% was male. Implantable cardioverter-defibrillators were implanted for primary prevention in 53% (43.5-62.7). Overall, 24% (18.6-31.3) of patients received one or more appropriate ICD interventions (anti-tachycardia pacing or shocks) during 3.7 +/- 0.9 years: 22% (16.9-28.8) of patients with primary prevention in 3.3 +/- 0.3 years and 35% (26.6-45.2) of patients with secondary prevention in 4.3 +/- 1.2 years. Inappropriate shocks occurred in 25% (20.1-31.0) in 3.7 +/- 0.8 years and other, particularly lead-related complications in 26% (18.9-33.6) of patients in 3.8 +/- 0.8 years. All-cause mortality was 10% during 3.7 +/- 0.9 years. CONCLUSIONS: In ACHD, remarkably high rates of appropriate ICD therapy were reported, both in primary and secondary prevention. Because of the young age and lower death rates, the cumulative beneficial effects are likely greater in ACHD patients than in acquired heart disease patients. However, considering the high rates of inappropriate shocks and complications, case-by case weighing of costs and benefits, remains essential. PMID- 26873096 TI - Analysis of microstructures and macrotextures for different apple cultivars based on parenchyma morphology. AB - Fuji, Golden Delicious, and Jonagold parenchyma were imaged by confocal laser scanning microscopy to be extracted morphology characteristics, which were used to analyze the relationship with macrotexture of apples tested by penetration and compression. Before analyzing the relationship, the significantly different morphology parameters were reduced in dimensions by principal component analysis and were proved to be availably used for distinguishing the different apple cultivars. For compression results, cell did not absolutely determine the hardness in different apple cultivars, and the pore should also be taken into consideration. With the same size in cell feret diameter, the bigger the pore feret diameter was, the softer the apple became. If no difference existed in pore feret diameter size, the cultivar became harder with a narrower distribution in cell feret diameter. The texture parameters were compared with the roundness parameters in the same or inverse changing trends to explore the relationship. High correlations were found between the texture parameters (energy required in whole penetration (Wt), fracture force (Fp), crispness) and pore solidity (R(2) > 0.924, P < 0.001). Compactness of parenchyma played an important role in fruit texture. This research could provide the comprehension about relationship between microstructure and macrotexture of apple cultivars and morphological values for modeling apple parenchyma, contributing to numerical simulation for constitutive relation of fruit. PMID- 26873097 TI - Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease. AB - Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host based biomarkers may address the need for sensitive clinical diagnostics during the "window period" of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. IMPORTANCE: Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the development of post-treatment symptoms, we conducted the first longitudinal gene expression (transcriptome) study of patients enrolled at the time of diagnosis and followed up for up to 6 months after treatment. Importantly, we found that the gene expression signature of early Lyme disease is distinct from that of other acute infectious diseases and persists for at least 3 weeks following infection. This study also uncovered multiple previously undescribed pathways and genes that may be useful in the future as human host biomarkers for diagnosis and that constitute potential targets for the development of new therapies. PMID- 26873098 TI - The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans. AB - PURPOSE: To evaluate the plasma bioavailability of betanin and nitric oxide (NOx) after consuming beetroot juice (BTJ) and whole beetroot (BF). BTJ and BF were also analysed for antioxidant capacity, polyphenol content (TPC) and betalain content. METHODS: Ten healthy males consumed either 250 ml of BTJ, 300 g of BF or a placebo drink, in a randomised, crossover design. Venous plasma samples were collected pre (baseline), 1, 2, 3, 5 and 8 h post-ingestion. Betanin content in BTJ, BF and plasma was analysed with reverse-phase high-performance liquid chromatography (HPLC) and mass spectrometry detection (LCMS). Antioxidant capacity was estimated using the Trolox equivalent antioxidant capacity (TEAC) and polyphenol content using Folin-Ciocalteu colorimetric methods [gallic acid equivalents (GAE)] and betalain content spectrophotometrically. RESULTS: TEAC was 11.4 +/- 0.2 mmol/L for BTJ and 3.4 +/- 0.4 MUmol/g for BF. Both BTJ and BF contained a number of polyphenols (1606.9 +/- 151 mg/GAE/L and 1.67 +/- 0.1 mg/GAE/g, respectively), betacyanins (68.2 +/- 0.4 mg/betanin equivalents/L and 19.6 +/- 0.6 mg/betanin equivalents/100 g, respectively) and betaxanthins (41.7 +/- 0.7 mg/indicaxanthin equivalents/L and 7.5 +/- 0.2 mg/indicaxanthin equivalents/100 g, respectively). Despite high betanin contents in both BTJ (~194 mg) and BF (~66 mg), betanin could not be detected in the plasma at any time point post-ingestion. Plasma NOx was elevated above baseline for 8 h after consuming BTJ and 5 h after BF (P < 0.05). CONCLUSIONS: These data reveal that BTJ and BF are rich in phytonutrients and may provide a useful means of increasing plasma NOx bioavailability. However, betanin, the major betalain in beetroot, showed poor bioavailability in plasma. PMID- 26873099 TI - Association between dietary carbohydrate intake, glycemic index and glycemic load, and risk of gastric cancer. AB - PURPOSE: The association between dietary carbohydrate intake, glycemic index (GI) and glycemic load (GL), and risk of gastric cancer (GC) has been investigated by many studies. However, the results of these studies were controversial. The aim of our study was to systematically assess this issue. METHODS: PUBMED and EMBASE were searched up to March 2015, and either a fixed- or a random-effects model was adopted to estimate overall relative risks (RRs). Dose-response, meta-regression, subgroup, and publication bias analyses were applied. RESULTS: Twenty-six studies with approximately 540,000 participants were finally included in this meta analysis. High level of dietary carbohydrate intake (pooled RR 1.17, 95 % CI 0.91 1.50), GI (pooled RR 1.17, 95 % CI 0.80-1.69), and GL (pooled RR 1.06, 95 % CI 0.90-1.26) were all nonsignificantly associated with incidence of GC. In addition, no significant dose-response relationship was observed between carbohydrate intake, GI and GL, and the risk of GC. However, further subgroup analyses based on gender and geographic region suggested a significant association between higher carbohydrate intake (pooled RR 1.52, 95 % CI 1.10 2.08), GL (pooled RR 1.41, 95 % CI 1.04-1.92), and GC risk in males subgroup, and between higher carbohydrate intake (pooled RR 1.69, 95 % CI 1.36-2.09) and GC risk in Asian studies. CONCLUSIONS: No significant association was found between dietary carbohydrate intake, GI and GL, and risk of GC. However, significantly positive association was observed in the males subgroup and Asian studies. PMID- 26873100 TI - Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory. AB - We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging. PMID- 26873101 TI - Synovial fluid detection in intra-articular injections using a bioimpedance probe (BIP) needle-a clinical study. AB - Intra-articular glucocorticoid injections are the recommended treatment for active arthritis, but accurate positioning of the needle may be challenging. Inexperienced physicians might decide not to inject because an unsuccessful injection impairs clinical outcome and may lead to complications; however, choosing not to inject may impair or delay the best possible treatment. Here, we address this problem by introducing a novel Bioimpedance Probe (BIP) Needle guidance method that was tested in a clinical study. The BIP Needle was utilized for detection of synovial fluid. It measures real-time bioimpedance spectra and identifies when the needle tip is in contact with the synovial fluid. Injections into 80 joints with active arthritis were performed by an experienced rheumatologist using the BIP Needle. The location of the BIP Needle was ensured by aspiration of synovial fluid, absence of resistance during injection, and/or using real-time ultrasound imaging. Sensitivity and specificity of the device for synovial fluid detection were 86 % (CI 75-93 %) and 85 % (CI 74-92 %), respectively. The BIP Needles showed high spatial resolution and differentiated the synovial fluid from the surrounding tissues. However, lack of synovial fluid, anatomic variability, and intra-articular structures challenged the technology. The BIP Needles provided adequate results in intra-articular injections. Performance of the device was good even in small joints, which may be the most difficult for inexperienced physicians. Further performance improvement can be expected when more data is collected for mathematical models. Overall, this novel method showed potential to be used in real-time needle guidance. PMID- 26873102 TI - The significance of urinary beta-2 microglobulin level for differential diagnosis of familial Mediterranean fever and acute appendicitis. AB - The clinical and laboratory parameters widely used are not specific to discriminate the abdominal pain due to FMF attack from that of acute appendicitis. The present study aims to investigate the urinary beta-2 microglobulin (U-beta2M) level as a potential parameter to identify these two diseases mimicking each other. A total of 51 patients with established FMF diagnosis due to Tel Hashomer criteria on colchicine treatment (1-1.5 mg/day), 15 patients with acute appendicitis who had appropriate clinical picture and were also supported pathologically after the surgery, and 20 healthy controls were enrolled in the study. Of the 51 patients with FMF, 25 were at an attack period, while remaining 26 were not. For the diagnosis of acute attack, as well as physical examination, laboratory tests including white blood cell count, C reactive protein, and erythrocyte sedimentation rate were performed. From urine specimens U-beta2M, microalbumin, and N-acetyl glucosaminidase (U-NAG) were measured. U-beta2M levels were significantly higher in acute appendicitis group compared to FMF attack, FMF non-attack, and control groups (p < 0.001, p < 0.001, and p < 0.001, respectively). U-NAG and microalbuminuria were significantly higher in acute appendicitis, FMF attack, and FMF non-attack groups compared to controls (U-NAG p < 0.001, p = 0.016, p = 0.004, microalbuminuria p < 0.001, p < 0.001, p < 0.001, respectively). Microalbuminuria was significantly higher in acute appendicitis group compared to the FMF attack group (p = 0.004). Determination of U-beta2M levels may be helpful for differential diagnosis of peritonitis attacks of FMF patients on colchicine treatment and acute appendicitis. However, this finding should be substantiated with other studies. PMID- 26873103 TI - Particulate and non-particulate steroids in spinal epidurals: a systematic review and meta-analysis. AB - BACKGROUND: Steroids in transforaminal epidural injections are widely used to ease radicular pain in both cervical and lumbar radiculopathy. Concerns have been articulated about the use of particulate steroids for this intervention, as a number of case reports have been published linking them with post procedural paralysis, possibly due to spinal ischaemia secondary to a steroid particulate embolism. Non-particulate, or soluble steroids, are mooted as an alternative; however, their effectiveness relative to particulate steroids has not been conclusively proven. STUDY DESIGN: We review the evidence in the published literature regarding the efficacy of non-particulate steroids in epidural injections compared to particulate steroids, and synthesise it to gauge the qualitative outcomes from level one evidence (visual analogue scales, numerical pain scores and Oswestry Disability Index) from baseline to specified follow up. METHODS: The PRISMA guidelines were utilised for this review. An internet search was performed to collate the available literature from medical databases PubMed, EMBASE, Web of Science and the Cochrane library. We used a broad search term [epidural (and) steroid] to ensure a wide capture of articles. No limitations in terms of language or date of publication were implemented. The reference lists of articles included for full text review were searched for any additional primary or review publications. RESULTS: Four online libraries were searched, with a combined total of 11,353 titles reviewed, not excluding duplicates. Post title abstract and full text review, nine articles were identified as suitable for inclusion for qualitative synthesis. Four of these were suitable for quantitative synthesis, with a total of 300 participants, 147 in the particulate group and 153 in the non-particulate group. Using a random effects model, the pooled standard mean difference of VAS score diminution was not significant between groups (0.31 in favour of particulates, 95 % CI -0.68 to 1.30). From our qualitative synthesis, there was a trend for greater improvement in pain scores within the particulate group. The type of steroid used did not appear to have an effect on the disability score given by patients. CONCLUSION: Particulate steroids are not demonstrably better in relieving pain compared to their non-particulate counterparts. In view of the concerns over the safety profile of particulate steroids, it may be prudent to switch to non particulates, or at the very least the dangers and alternatives should be flagged with the patient group as part of a shared decision making process. PMID- 26873104 TI - Morphometry of the lower lumbar intervertebral discs and endplates: comparative analyses of new MRI data with previous findings. AB - PURPOSE: Variability of the human lower lumbar geometry is related to complications of disc arthroplasty surgery. Accurate morphometric descriptions are essential for the design of artificial intervertebral discs to ensure good prothesis-vertebra contact and better load distribution, and can improve spinal biomechanics. Unfortunately, current knowledge of the lower lumbar geometry is limited either in the representativeness of sample populations or the accuracy and comprehensiveness of measurements. The objective of this study was to establish an accurate and reliable measurement protocol, provide a comprehensive database of lower lumbar geometry, and compare and summarize geometric data as reported in the literature. METHODS: T2-weighted magnetic resonance imaging (MRI) scans of lower lumbar spine (L3-S1), taken from 109 adult subjects, were anonymized from the digital archive of a local hospital. A total of 318 intervertebral discs and 590 endplates met the inclusion criteria and were studied. Linear and planar measurements were performed using OsiriX software, and analyzed using split plot factorial (SPF) analysis of variance (ANOVA), independent student t tests, paired sample t tests, and Tukey's honest significant difference (HSD) post hoc tests. RESULTS: Excellent intra- and inter observer reliabilities were achieved using the proposed measurement protocol. The results of this study indicated that male subjects had significantly larger geometric dimensions. L5/S1 discs had the smallest geometric dimensions compared to the discs at other two levels. Significant craniocaudal differences were found in endplate morpohometry. The error associated with using ellipsoid methods was quantified at each lower lumbar level. A large comprehensive database compiling lower lumbar geometry from many studies was established. This study provides geometric data for the female subjects at the L5/S1 level, previously lacking in the literature. CONCLUSION: This study demonstrates the potential of using MRI data to establish a standard measurement protocol for morphometric quantification of the lower lumbar intervertebral discs and vertebral endplates. These results are invaluable in characterizing comprehensive lower lumbar morphometry, which may provide crucial information for planning spinal surgeries, designing artificial intervertebral discs, and for biomechanical modeling of the low lack. PMID- 26873105 TI - Novel actin filaments from Bacillus thuringiensis form nanotubules for plasmid DNA segregation. AB - Here we report the discovery of a bacterial DNA-segregating actin-like protein (BtParM) from Bacillus thuringiensis, which forms novel antiparallel, two stranded, supercoiled, nonpolar helical filaments, as determined by electron microscopy. The BtParM filament features of supercoiling and forming antiparallel double-strands are unique within the actin fold superfamily, and entirely different to the straight, double-stranded, polar helical filaments of all other known ParMs and of eukaryotic F-actin. The BtParM polymers show dynamic assembly and subsequent disassembly in the presence of ATP. BtParR, the DNA-BtParM linking protein, stimulated ATP hydrolysis/phosphate release by BtParM and paired two supercoiled BtParM filaments to form a cylinder, comprised of four strands with inner and outer diameters of 57 A and 145 A, respectively. Thus, in this prokaryote, the actin fold has evolved to produce a filament system with comparable features to the eukaryotic chromosome-segregating microtubule. PMID- 26873107 TI - Assessing Circulating Factor VIIa-Antithrombin Complexes in Acute Ischemic Stroke: A Pilot Study. AB - AIM: The goal of this study was to determine the levels of factor VII (FVII), factor VIIa-antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. METHODS: Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. RESULTS: Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). CONCLUSION: Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels. PMID- 26873106 TI - Transcription-associated processes cause DNA double-strand breaks and translocations in neural stem/progenitor cells. AB - High-throughput, genome-wide translocation sequencing (HTGTS) studies of activated B cells have revealed that DNA double-strand breaks (DSBs) capable of translocating to defined bait DSBs are enriched around the transcription start sites (TSSs) of active genes. We used the HTGTS approach to investigate whether a similar phenomenon occurs in primary neural stem/progenitor cells (NSPCs). We report that breakpoint junctions indeed are enriched around TSSs that were determined to be active by global run-on sequencing analyses of NSPCs. Comparative analyses of transcription profiles in NSPCs and B cells revealed that the great majority of TSS-proximal junctions occurred in genes commonly expressed in both cell types, possibly because this common set has higher transcription levels on average than genes transcribed in only one or the other cell type. In the latter context, among all actively transcribed genes containing translocation junctions in NSPCs, those with junctions located within 2 kb of the TSS show a significantly higher transcription rate on average than genes with junctions in the gene body located at distances greater than 2 kb from the TSS. Finally, analysis of repair junction signatures of TSS-associated translocations in wild type versus classical nonhomologous end-joining (C-NHEJ)-deficient NSPCs reveals that both C-NHEJ and alternative end-joining pathways can generate translocations by joining TSS-proximal DSBs to DSBs on other chromosomes. Our studies show that the generation of transcription-associated DSBs is conserved across divergent cell types. PMID- 26873108 TI - The Impact of CYP2C19 Loss-of-Function Polymorphisms, Clinical, and Demographic Variables on Platelet Response to Clopidogrel Evaluated Using Impedance Aggregometry. AB - INTRODUCTION: Clopidogrel is an antiplatelet drug widely used in patients with acute coronary syndromes or stroke. Despite adequate antiplatelet therapy, some patients develop acute ischemic events. This is partly attributed to the fact that they have poor inhibition of platelet reactivity, despite treatment. This study aimed to assess the impact of clinical and demographic variables and of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms on platelet response to clopidogrel evaluated using impedance aggregometry in an East European population. METHODS: The study included 189 clopidogrel-treated patients with acute coronary syndromes and noncardiogenic ischemic stroke. Platelet aggregation was evaluated by impedance aggregometry. CYP2C19 loss-of-function polymorphisms were detected using the polymerase chain reaction restriction fragment length polymorphism technique. Various clinical and demographic data were also recorded. RESULTS: In our data set, 81% of the patients were responders and 19% nonresponders to clopidogrel therapy. The distribution of CYP2C19 polymorphisms was as follows: 61.1% of patients were CYP2C19 wild-type homozygotes, 27.7% of patients were CYP2C19*2 heterozygotes, 1.1% of patients were CYP2C19*3 heterozygotes, and 10% of patients were CYP2C19*2 homozygotes. The highest level of association with clopidogrel response status was found for CYP2C19 polymorphisms, concomitant aspirin treatment, leukocyte and platelet count, history of myocardial infarction, arterial hypertension, and ward where patients were admitted. CONCLUSION: The prevalence of clopidogrel resistance in our East European population was in line with that reported for Western populations. Clopidogrel response was significantly influenced by the presence of CYP2C19 polymorphisms. Interestingly, the concomitant use of aspirin had a significant impact on platelet response to clopidogrel, indicating a synergic interaction between these drugs. PMID- 26873109 TI - Fractal analysis of extra-embryonic vessels of chick embryos under the effect of glucosamine and chondroitin sulfates. AB - Like heparan sulfate proteoglycans, some monosaccharides and glycosaminoglycans, such as sulfated glucosamine (GS) and chondroitin (CS), integrate the vascular extracellular matrix and may influence vascular endothelial cell growth. To assess the effects of these substances on blood vessel formation, we used the chick yolk sac membrane (YSM) model and fractal geometry quantification, which provided an objective in vivo method for testing potential agents that promote vasculogenesis and angiogenesis. An image processing method was developed to evaluate YSM capillary vessels after they were implanted in a methylcellulose disk of GS or CS at a concentration between 0.001-0.1mg/disk (performed on 2-day old embryos). This method resulted in a binary image of the microvascular network (white vessels on a black background). Fractal box-counting (DBC) and information (DINF) dimensions were used to quantify the activity of GS and CS in vasculogenesis and angiogenesis. YSM treated with GS (0.001-0.1mg) and CS (0.03 0.1mg) showed an increase in fractal dimensions that corresponded to vitelline vessel growth compared to the control group (vehicle), with GS displaying higher fractal dimension values. PMID- 26873110 TI - Discriminating between two autonomic profiles related to posture in Olympic athletes. AB - PURPOSE: Autonomic assessment might be useful in training management. We planned to assess whether oscillatory metrics of RR variability (such as LFnu) would be more efficient than static indices from low order statistics (RR variance) at discriminating laying rest from stand posture, as an analog of a shift to sympathetic dominance. METHODS: We studied a large population of elite Olympic athletes: a total of 406 athletes (162 females and 244 males, of similar age 21.7 and 24.4 years) participating to the selection for the upcoming 2016 Olympic games. We employed various methods to extract autonomic indices from RR variability and employed a stepwise statistical approach combining factor and discriminant analysis. RESULTS: We observed that that relative power of oscillatory components from spectral analysis of RR variability (such as LF or HF in nu) and indices from symbolic analysis (particularly 0V) clearly outperform RR variance in discriminating between two physiological conditions (laying rest and stand) related to posture and autonomic activation. CONCLUSIONS: In world class Olympic athletes we have shown that a small subset of RR variability indices, related to sympathovagal balance, may be more appropriate than RR variance to assess excitatory sympathetic autonomic responsiveness of the SA node. These findings may have practical implications for the use of RR variability in guiding training and predicting success in competitions. PMID- 26873111 TI - A Well-Differentiated Mediastinal Liposarcoma from the Posterior Mediastinum with Separated Solid and Lipomatous Regions: A Case Report. PMID- 26873112 TI - Clinical Decision Support Reduces Overuse of Red Blood Cell Transfusions: Interrupted Time Series Analysis. AB - BACKGROUND: Red blood cell transfusion is the most common procedure in hospitalized patients in the US. Growing evidence suggests that a sizeable percentage of these transfusions are inappropriate, putting patients at significant risk and increasing costs to the health care system. METHODS: We performed a retrospective quasi-experimental study from November 2008 until November 2014 in a 576-bed tertiary care hospital. The intervention consisted of an interruptive clinical decision support alert shown to a provider when a red blood cell transfusion was ordered in a patient whose most recent hematocrit was >=21%. We used interrupted time series analysis to determine whether our primary outcome of interest, rate of red blood cell transfusion in patients with hematocrit >=21% per 100 patient (pt) days, was reduced by the implementation of the clinical decision support tool. The rate of platelet transfusions was used as a nonequivalent dependent control variable. RESULTS: A total of 143,000 hospital admissions were included in our analysis. Red blood cell transfusions decreased from 9.4 to 7.8 per 100 pt days after the clinical decision support intervention was implemented. Interrupted time series analysis showed that significant decline of 0.05 (95% confidence interval [CI], 0.03-0.07; P < .001) units of red blood cells transfused per 100 pt days per month was already underway in the preintervention period. This trend accelerated to 0.1 (95% CI, 0.09-0.12; P < .001) units of red blood cells transfused per 100 pt days per month following the implementation of the clinical decision support tool. There was no statistical change in the rate of platelet transfusion resulting from the intervention. CONCLUSIONS: The implementation of an evidence-based clinical decision support tool was associated with a significant decline in the overuse of red blood cell transfusion. We believe this intervention could be easily replicated in other hospitals using commercial electronic health records and a similar reduction in overuse of red blood cell transfusions achieved. PMID- 26873113 TI - Elevated plasma levels of vascular permeability factors in C1 inhibitor-deficient hereditary angioedema. AB - BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited genetic disease characterized by recurrent swelling episodes of the skin, gastrointestinal tract, and upper airways. Angioedema attacks result from increased vascular permeability due to the release of bradykinin from high molecular weight kininogen. Currently, there are no biomarkers predicting the frequency of angioedema attacks. Vascular permeability is modulated by several factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (Angs). As increased circulating levels of VEGFs and Angs have been observed in diseases associated with higher vascular permeability (e.g., systemic capillary leak syndrome and sepsis), we sought to analyze plasma concentrations of VEGFs and Angs in patients with C1-INH-HAE. METHODS: Sixty-eight healthy controls and 128 patients with C1-INH-HAE were studied. Concentrations of angiogenic (VEGF-A, Ang1, Ang2), anti-angiogenic (VEGF-A165b ) and lymphangiogenic (VEGF-C) factors were evaluated by ELISA. C1-INH functional activity was assessed by EIA. RESULTS: Plasma concentrations of VEGF-A, VEGF-C, Ang1, and Ang2 were higher in patients with C1-INH-HAE in remission than in healthy controls. Concentration of VEGF-A was further increased in patients with lower C1-INH functional activity. Patients with C1-INH-HAE experiencing more than 12 angioedema attacks per year were characterized by higher plasma levels of VEGF-A, VEGF-C, and Ang2 compared with the other patients. CONCLUSIONS: We hypothesize that VEGFs and Angs induce a state of 'vascular preconditioning' that may predispose to angioedema attacks. In addition, the identification of increased plasma levels of VEGFs and Angs in patients with C1-INH-HAE may prompt the investigation of VEGFs and Angs as biomarkers of C1-INH-HAE severity. PMID- 26873114 TI - Tandem repeat knockout utilizing the CRISPR/Cas9 system in human cells. AB - Tandem repeats have been shown to cause human genetic diseases and contribute significantly to genome variation and instability. Although multi-sgRNAs mediated CRISPR/Cas9 system have used to generate regional deletions previously, in this study we explored a method of generating regional deletions of tandem repeats by taking advantage of the off-target effects of CRISPR/Cas9 in 293FT cells. Our results revealed that generation of large-fragment deletions of tandem repeats located in the MAGEL2 and XIST gene was possible. In summary, we have demonstrated that large-fragment deletions of tandem repeats can be achieved using a sgRNA-directed CRISPR/Cas9 system, facilitating the functional study of tandem repeats in future studies. PMID- 26873115 TI - The involvement of mutant Rac1 in the formation of invadopodia in cultured melanoma cells. AB - In this article, we discuss the complex involvement of a Rho-family GTPase, Rac1, in cell migration and in invadopodia-mediated matrix degradation. We discuss the involvement of invadopodia in invasive cell migration, and their capacity to promote cancer metastasis. Considering the regulation of invadopodia formation, we describe studies that demonstrate the role of Rac1 in the metastatic process, and the suggestion that this effect is attributable to the capacity of Rac1 to promote invadopodia formation. This notion is demonstrated here by showing that knockdown of Rac1 in melanoma cells expressing a wild-type form of this GTPase, reduces invadopodia-dependent matrix degradation. Interestingly, we also show that excessive activity of Rac1, displayed by the P29S, hyperactive, "fast cycling" mutant of Rac1, which is present in 5-10% of melanoma tumors, inhibits invadopodia function. Moreover, knockdown of this hyperactive mutant enhanced matrix degradation, indicating that excessive Rac1 activity by this mutant can negatively regulate invadopodia formation and function. PMID- 26873117 TI - Editor's perspectives--February 2016. PMID- 26873116 TI - Aerobic biosynthesis of hydrocinnamic acids in Escherichia coli with a strictly oxygen-sensitive enoate reductase. AB - 3-Phenylpropionic acid (3PPA) and 3-(4-hydroxyphenyl) propionic acid (HPPA) are important commodity aromatic acids widely used in food, pharmaceutical and chemical industries. Currently, 3PPA and HPPA are mainly manufactured through chemical synthesis, which contains multiple steps involving toxic solvents and catalysts harmful to environment. Therefore, replacement of such existing petroleum-derived approaches with simple and environmentally friendly biological processes is highly desirable for manufacture of these chemicals. Here, for the first time we demonstrated the de novo biosynthesis of 3PPA and HPPA using simple carbon sources in E. coli by extending the cinnamic acids biosynthesis pathways through biological hydrogenation. We first screened 11 2-enoate reductases (ER) from nine microorganisms, leading to efficient conversion of cinnamic acid and p coumaric acid to 3PPA and HPPA, respectively. Surprisingly, we found a strictly oxygen-sensitive Clostridia ER capable of functioning efficiently in E. coli even under aerobic conditions. On this basis, reconstitution of the full pathways led to the de novo production of 3PPA and HPPA and the accumulation of the intermediates (cinnamic acid and p-coumaric acid) with cell toxicity. To address this problem, different expression strategies were attempted to optimize individual enzyme's expression level and minimize intermediates accumulation. Finally, the titers of 3PPA and HPPA reached 366.77mg/L and 225.10mg/L in shake flasks, respectively. This study not only demonstrated the potential of microbial approach as an alternative to chemical process, but also proved the possibility of using oxygen-sensitive enzymes under aerobic conditions. PMID- 26873118 TI - Diagnostic value of telecytology in tertiary teledermatological consultation: a retrospective analysis of 75 cases. AB - BACKGROUND: The addition of dermatoscopic images to clinical images is reported to increase the diagnostic value of teledermatology. No study has investigated the contribution of telecytology to teledermatology. We aimed to assess the diagnostic accuracy of telecytology in tertiary teledermatological evaluation. METHODS: The study included 75 patients for whom no diagnosis could be established at face-to-face clinical examinations and cytological evaluations, who therefore consulted with a dermatologist experienced in cytology through the store-and-forward method. Telecytological diagnosis was then compared with the final diagnosis, and diagnostic accuracy was calculated. RESULTS: In the past 2 years, 75 patients (38 [50.7%] female, 37 [49.3%] male) were evaluated by telecytology. According to definitive diagnoses, 31 patients (41.3%) had erosive vesiculobullous, 25 (33.3%) had tumoral, and 19 (15.8%) had granulomatous disease. Diagnostic accuracy of telecytology was 90.7%. LIMITATIONS: Our study was a retrospective study, and cytological images were evaluated by one dermatologist only; therefore, no reliability analysis could be performed. CONCLUSION: This study revealed that the cytological images should be used in tertiary teledermatological evaluation. Further studies should therefore be carried out to investigate the diagnostic value of different telecytological methods. PMID- 26873119 TI - Development of the synganglion and morphology of the adult nervous system in the mite Archegozetes longisetosus Aoki (Chelicerata, Actinotrichida, Oribatida). AB - Small arthropods show a highly condensed central nervous system, which is accompanied by the loss of the ancestral metameric organization. This results in the formation of one solid mass, a synganglion. Although numerous studies investigated the morphology of Archegozetes longisetosus, the organization of the nervous system is to date unknown. Using synchrotron X-ray microtomography, we investigated the organization of the nervous system in the adult stage and the development of the synganglion over all five free-living life stages (larva, proto-, deuto-, tritonymph and adult). The general morphology of the synganglion resembles that of other studied mites (in the classic sense) and ticks, being subdivided into a sub- and supraesophageal region, and consisting of cortex and neuropil. All nerves entering the walking legs except the first consist of two rami. This split is not based on a functional division into a motor and a sensory ramus, but both rami contain motor and sensory neurites. Within the synganglion, we found structures that resemble the ancestral metameric organization of the nervous system of arthropods. The development of the synganglion of A. longisetosus shows a more or less linear increase in volume, but cortex and neuropil grow at different rates over the five life stages. Between the second and third nymphal stage, the volume of the neuropil increases at a faster rate than the cortex. PMID- 26873120 TI - Success rates of single-dose methotrexate and additional dose requirements among women with first and previous ectopic pregnancies. AB - OBJECTIVE: To compare the success of the single-dose methotrexate regimen and the requirement for a second or third dose of methotrexate between women with their first ectopic pregnancy (EP) and those with previous EP. METHODS: In a retrospective cohort study, data were analyzed from women treated for EP by single-dose methotrexate at a Turkish tertiary referral center between January 2010 and December 2013. Data were compared between women with at least one previous EP and those with their first EP. RESULTS: The success rate of the protocol in the first and previous EP groups was similar: 93.0% (320/344) and 87.3% (48/55), respectively. History of previous EP was not a predictor of treatment failure. However, the requirement for additional methotrexate doses was significantly higher in the previous EP group (16/48 [33.4%]) than in the first EP group (55/320 [17.2%]; P=0.03). Multivariate analysis showed that history of tubal surgery (P=0.006) and initial levels of the beta-subunit of human chorionic gonadotropin (P=0.001) were significant predictors of treatment failure. CONCLUSION: Although the single-dose regimen had similar success rates in the previous EP and first EP groups, additional doses of methotrexate were more frequently required in the previous EP group. PMID- 26873121 TI - High dependency unit admissions during the first year of a national obstetric early warning system. PMID- 26873124 TI - Clinician attendance and delivery practices at hospital-based vaginal deliveries in Western Kenya. AB - OBJECTIVE: To characterize delivery practices and factors associated with respectful, evidence-based care at a referral hospital in Western Kenya. METHODS: An exploratory observational study used a standardized birth-observation form to record information on patient characteristics and healthcare practitioner behaviors during uncomplicated vaginal deliveries between June 30, 2014 and July 17, 2014. All deliveries were monitored for whether healthcare staff performed six specific evidence-based practices (three maternal and three neonatal practices). RESULTS: In total, 75 vaginal deliveries were observed. In 48 (64%) deliveries, nursing students were the only practitioners present. The mean number of evidence-based practices performed at each delivery was 3.58. The number of evidence-based practices performed by junior practitioners was higher when a nurse educator was assessing their performance (4.47 vs 3.36, P<0.001). Lower mean respectful-care scores were recorded when delivery teams comprised three or more practitioners (1.38; 95% confidence interval 0.93-1.84 vs 2.74; 95% confidence interval 2.16-3.31, P=0.002). CONCLUSION: The present study found low rates of evidence-based practice and respectful maternity care; this could serve as a deterrent for women seeking care at the study facility. These findings emphasize the need for a comprehensive approach in increasing the quality of patient care to improve maternal and newborn health outcomes. PMID- 26873123 TI - Effect of subsequent pregnancies on HIV disease progression among women in the Mulago Hospital MTCT-Plus program in Uganda. AB - OBJECTIVE: To investigate the effect of subsequent pregnancies on HIV disease progression among HIV-infected women at Mulago Hospital, Uganda. METHODS: In a retrospective cohort study, data were analyzed from women enrolled in the Mother To-Child Transmission Plus program from March 2003 to December 2011. The CD4 cell count, the development of new AIDS-defining opportunistic infections, and the AIDS-related mortality were compared between women with and without subsequent pregnancies. RESULTS: Overall, 409 women were enrolled and 195 (47.7%) had subsequent pregnancies. Antiretroviral therapy (ART) was initiated in 143 (73.3%) women with and 155 (72.4%) women without subsequent pregnancies. Kaplan-Meier analysis for women receiving ART showed no differences between women with and without subsequent pregnancies in the median times to clinical failure (62.7 vs 64.7 months; P=0.31), immunological failure (68.8 vs 75.5 months; P=0.10), and death (68.8 vs 75.5 months; P=0.53). In a Cox regression analysis, subsequent pregnancies were not associated with immunological failure during follow-up (adjusted hazard ratio 1.13, 95% confidence interval 0.06-2.09). CONCLUSION: Subsequent pregnancies could have no detrimental effect on HIV disease progression among HIV-infected women whose treatment is well managed. PMID- 26873122 TI - Intimate partner violence among married couples in India and contraceptive use reported by women but not husbands. AB - OBJECTIVE: To assess whether intimate partner violence (IPV) is associated with discordant reports of contraceptive use (whereby wives but not husbands report such use) among married couples in Maharashtra, India. METHODS: The present cross sectional study in rural Maharashtra, India, analyzed survey data collected in 2012 among husbands and wives aged 18-30 years, fluent in Marathi, with no prior sterilization, and with no current pregnancy or plans to conceive. Crude and adjusted logistic regression models assessed husbands' perpetration of IPV in relation to discordant reports of contraceptive use. RESULTS: Among 577 couples meeting the eligibility criteria, 207 (35.9%) women reported ever experiencing physical IPV from their husbands, and 183 (31.7%) reported ever experiencing sexual IPV from their husbands. In adjusted logistic regression models, discordant contraceptive use was significantly associated with wives' experiences of physical IPV (adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.15-4.42) and sexual IPV (AOR 1.95, 95% CI 1.08-4.82). CONCLUSION: Women who reported IPV from their husbands might be more likely to use contraceptives without informing their husbands, possibly to redress the reproductive control often exerted by abusive male partners. PMID- 26873125 TI - Anti-Mullerian hormone concentrations and antral follicle counts for the prediction of pregnancy outcomes after intrauterine insemination. AB - OBJECTIVE: To evaluate anti-Mullerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination. METHODS: A retrospective study included women with unexplained infertility aged 41years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression. RESULTS: Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3ng/mL (odds ratio 5.84, 95% confidence interval 2.38-14.31; P<0.001). No associations were recorded for AFCs. CONCLUSION: AMH should be used to predict the pregnancy outcome of intrauterine insemination. PMID- 26873126 TI - Husbands' experiences and perceptions regarding the use of maternity waiting homes in rural Zambia. AB - OBJECTIVE: To explore men's experience and beliefs regarding the use of maternity waiting homes (MWHs) in Kalomo District, Zambia. METHODS: As part of a qualitative study, in-depth interviews with the husbands/partners of women attending the under-five clinic at a health center with a MWH were conducted between April 1 and May 31, 2014. Men aged 18-50 years whose partner/wife was of reproductive age and who had lived in the area for more than 6 months were eligible for inclusion. RESULTS: Overall, 24 husbands/partners were interviewed in seven rural health centers. Men perceived many potential benefits of MWHs, including improved access to facility-based skilled delivery services and treatment in case of labor complications. Their many roles included decision making and securing funds for transport, food, cleaning materials, and clothes for the mother and the neonate to use during and after labor. However, limited financial resources made it difficult for them to provide for their wives and newborns, and usually led to delays in their decisions about MWH use. Poor conditions in MWHs and the lack of basic social and healthcare needs meant some men had forbidden their wives/partners from using the facilities. CONCLUSION: Important intervention targets for improving access to MWHs and skilled birth attendance have been identified. PMID- 26873127 TI - Evidence from cluster surveys on the association between home-based counseling and use of family planning in conflict-affected Darfur. AB - OBJECTIVE: To examine the association between home counseling and awareness and use of modern family planning (FP) methods among women in internally displaced person (IDP) camps in conflict-affected West Darfur, Sudan. METHODS: In a community-based cross-sectional study, two questionnaire-based surveys were performed in three camps. Home-based counseling had been introduced in March 2006. An initial survey (February 2007) and a follow-up survey (April 2009) targeted women of child-bearing age. A sample of 640 randomly selected women aged 15-49 years who had experienced pregnancy after joining the camp were interviewed for each survey. RESULTS: Overall, modern FP use increased from 10.9% (70/640) in 2007 to 21.6% (138/640) in 2009 (P<0.001). As compared with the initial survey, women in the follow-up survey were more likely to be aware of and to use any modern FP method (adjusted odds ratio [aOR] 5.4, 95% confidence interval [CI] 3.9 7.4; and aOR 2.8, 95% CI 2.0-4.1, respectively). Contraceptive pills were the most common modern method used. Home counseling and loss of a child under 5years were the most significant predictors of awareness and use of modern FP methods. CONCLUSION: After the introduction of home-based FP counseling for couples and FP services in clinics, women's awareness and use of modern FP methods increased in a conflict-affected setting. PMID- 26873128 TI - Evaluation of the systemic inflammatory response syndrome criteria for the diagnosis of sepsis due to maternal bacteremia. AB - OBJECTIVE: To examine, in the setting of maternal bacteremia, the implications for the diagnosis of maternal sepsis of customizing the systemic inflammatory response syndrome (SIRS) criteria for physiologic changes of pregnancy. METHODS: Women with maternal bacteremia in a tertiary maternity hospital during 2009-2014 were identified. Records were retrospectively reviewed to determine whether they fulfilled the criteria for diagnosis of sepsis based on either the standard SIRS parameters derived from the Surviving Sepsis Campaign or SIRS parameters customized for pregnancy. Diagnosis of sepsis was based on the presence of two or more SIRS criteria, in conjunction with infection, during the hour before and the 6 hours after phlebotomy for blood culture. RESULTS: Of 93 women with bacteremia, 61 (66%) would have been diagnosed with sepsis based on standard criteria compared with 52 (56%) based on customized criteria (P=0.18). Seventeen women had a diagnosis of sepsis based on the standard but not the customized criteria, while eight women had sepsis based on the customized but not the standard criteria. CONCLUSION: In maternal bacteremia, customized SIRS criteria do not increase the rate of diagnosis of sepsis. Prospective studies should investigate whether the introduction of customized SIRS criteria can improve clinical outcomes. PMID- 26873129 TI - Social isolation in women with endometriosis and chronic pelvic pain. AB - OBJECTIVE: To evaluate the perceptions of women with endometriosis and chronic pelvic pain regarding their social ties. METHODS: A qualitative study was undertaken of women with chronic pelvic pain and endometriosis. Focus groups discussions among four to six participants were performed until saturation at the Clinics Hospital of Ribeirao Preto Medical School, Ribeirao Preto, southwest Brazil, between February 2013 and January 2014. Transcripts were analyzed according to the grounded theory approach and the emerging categories were coded using the WebQDA platform. RESULTS: Six focus group discussions took place, with a total of 29 patients. Social isolation was the main emerging theme. Social isolation was associated with a lack of understanding about endometriosis symptoms and with resignation in face of recurrent pain episodes. Avoiding partner intimacy and isolation from family and friends were components of social isolation. CONCLUSION: Women with endometriosis develop progressive social isolation after the onset of chronic pelvic pain. This finding is important for the multidisciplinary management of the disease. PMID- 26873130 TI - Violence against women must concern obstetrician-gynecologists. PMID- 26873131 TI - Legal and ethical issues of uterus transplantation. AB - The clinically detailed report of a successful uterus transplantation and live birth in Sweden, in which a family friend donated her uterus, provides a basis for expanded practice. Family members and friends can serve as living donors without offending legal or ethical prohibitions of paid organ donation, even though family members and friends often engage in reciprocal gift exchanges. Donations from living unrelated sources are more problematic, and there is a need to monitor donors' genuine altruism and motivation. Donation by deceased women i.e. cadaveric donation-raises issues of uterus suitability for transplantation, and how death is diagnosed. Organs' suitability for donation is often achieved by ventilation to maintain cardiac function for blood circulation, but laws and cultures could deem that a heartbeat indicates donors' live status. Issues could arise concerning ownership and control of organs between recovery from donors and implantation into recipients, and on removal following childbirth, that require legal resolution. PMID- 26873132 TI - Polypoid and fungating form of elephantiasic pretibial myxedema with involvement of the hands. PMID- 26873133 TI - Estrogen receptors modulate striatal metabotropic receptor type 5 in intact and MPTP male mice model of Parkinson's disease. AB - Glutamate is the most important brain excitatory neurotransmitter and glutamate overactivity is well documented in Parkinson's disease (PD). Metabotropic glutamate (mGlu) receptors are reported to interact with membrane estrogen receptors (ERs) and more specifically the mGlu5 receptor subtype. 17beta estradiol and mGlu5 antagonists have neuroprotective effects in the 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We previously reported that ERalpha and ERbeta are involved in neuroprotection following MPTP toxicity. The present study investigated the implication of ERs on the mGlu5 receptor adaptive response to MPTP toxicity in the brain of wild type (WT), ER knockout (ERKO)alpha and ERKObeta male mice. Autoradiography of [(3)H]ABP688 specific binding to striatal mGlu5 receptors showed a dorsal/ventral gradient similar for WT, ERKOalpha and ERKObeta mice with higher values ventrally. The lateral septum had highest [(3)H]ABP688 specific binding that remained unchanged in all experimental groups. ERKOalpha and ERKObeta mice had similarly lower striatal [(3)H]ABP688 specific binding than WT mice as measured also by Western blots. MPTP dose-dependently decreased striatal [(3)H]ABP688 specific binding in WT but not in ERKOalpha and ERKObeta mice; this correlated positively with striatal dopamine concentrations. A 17beta-estradiol treatment for 10 days left unchanged striatal [(3)H]ABP688 specific binding of unlesioned mice of the three genotypes. 17beta-estradiol treatment for 5 days before MPTP and for 5 days after partially prevented the mGlu5 receptor decrease only in WT MPTP mice and this was associated with higher BDNF striatal contents. These results thus show that in male mice ERs affect striatal mGlu5 receptor levels and their response to MPTP. PMID- 26873135 TI - Editorial overview: Folding and binding: Dynamic conformational heterogeneity is pivotal to cell life. PMID- 26873134 TI - Effect of steroid hormones, estrogen and progesterone, on epithelial mesenchymal transition in ovarian cancer development. AB - As the primary female sex steroid hormones, estrogens and progesterone play important roles to regulate growth, differentiation, and function of a broad range of target tissues in the human body and maintain the function of female reproductive tissues. Ovarian cancer is the most cause of cancer death in gynecological malignancy. Despite enormous outcomes in the understanding of ovarian cancer pathology, this disease has resulted in poor survival rates since most patients are asymptomatic until the disease has been metastasized. The exact molecular events leading to metastasis of ovarian tumor cells have not yet been well elucidated, although it is recognized that the acquisition of capacity for migration and invasiveness would be a necessary prerequisite. During metastasis, epithelial-mesenchymal transition (EMT) is an important process, in which epithelial cells lose their intracellular adhesion and cell polarity and acquire increased motility and invasive properties to become mesenchymal like cells. The process of cancer cells to undergo EMT is regulated through the up- and down- regulation of a multiple cellular markers and signaling proteins. In this review, we focused the roles of women sex steroid hormones, estrogen and progesterone, in ovarian cancer, especially the ovarian cancer undergoing EMT and metastatic process. All things considered, we may suggest that progesterone is a potent hormone which inhibits the growth of human ovarian cancer cells and development to metastasis whereas estrogen may act as a risk factor of ovarian cancer progression and that progesterone therapy may be an alternative clinically effective tool for the treatment of human ovarian cancer. PMID- 26873136 TI - Spheroid culture of LuCaP 136 patient-derived xenograft enables versatile preclinical models of prostate cancer. AB - LuCaP serially transplantable patient-derived xenografts (PDXs) are valuable preclinical models of locally advanced or metastatic prostate cancer. Using spheroid culture methodology, we recently established cell lines from several LuCaP PDXs. Here, we characterized in depth the features of xenografts derived from LuCaP 136 spheroid cultures and found faithful retention of the phenotype of the original PDX. In vitro culture enabled luciferase transfection into LuCaP 136 spheroids, facilitating in vivo imaging. We showed that LuCaP 136 spheroids formed intratibial, orthotopic, and subcutaneous tumors when re-introduced into mice. Intratibial tumors responded to castration and were highly osteosclerotic. LuCaP 136 is a realistic in vitro-in vivo preclinical model of a subtype of bone metastatic prostate cancer. PMID- 26873138 TI - Polarity correction factor for flattening filter free photon beams in several cylindrical ionization chambers. AB - In this study, we aimed to compare the polarity correction factor in ionization chambers for flattening filter free (FFF) photon beams and flattening filter (FF) beams. Measurements were performed with both 6 and 10 MV FFF and FF beams. Five commercial ionization chambers were evaluated: PTW TN30013; IBA Dosimetry CC01, CC04, and CC13; and Exradin A12S. Except for the CC01 ionization chamber, the other four chambers showed less than a 0.3 % difference in the polarity effect between the FFF and the FF beams. The CC01 chamber showed a strong field-size dependence, unlike the other chambers. The polarity effect for all chambers with FFF beams did not change with the dose rate. Except in the case of the CC01 chamber, the difference in the polarity effect between FFF and FF beams was not significant. PMID- 26873137 TI - Versican and vascular endothelial growth factor expression levels in peritoneal metastases from colorectal cancer are associated with survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. AB - Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can increase survival of colorectal cancer (CRC) patients with peritoneal metastases (PM). This treatment is associated with high morbidity and mortality rates. Therefore, improvement of patient selection is necessary. Assuming that the clinical phenotype is dictated by biological mechanisms, biomarkers could play a crucial role in this process. Since it is unknown whether and to what extent angiogenesis influences the course of disease in patients with PM, we investigated the expression of two angiogenesis-related markers and their relation to overall survival (OS) in CRC patients after CRS and HIPEC. Clinicopathological data and tissue samples were collected from 65 CRC patients with isolated metastases to the peritoneum that underwent CRS and HIPEC. Whole tissue specimens from PM were evaluated for versican (VCAN) expression, VEGF expression and microvessel density (MVD) by immunohistochemistry. The relation between these markers and OS was assessed using univariate and multivariate analysis. Associations between VEGF expression, VCAN expression, MVD and clinicopathological data were tested. High stromal VCAN expression was associated with high MVD (p = 0.001), better resection outcome (p = 0.003) and high T-stage (p = 0.027). High epithelial VCAN expression was associated with MVD (p = 0.007) and a more complete resection (p < 0.001). In multivariate analysis, simplified peritoneal cancer index (p = 0.001), VEGF expression levels (p = 0.012), age (p = 0.030), epithelial VCAN expression levels (p = 0.042) and lymph node status (p = 0.053) were associated with OS. Concluding, VCAN and VEGF were associated with survival in CRC patients with PM after CRS and HIPEC. Independent validation in a well-defined patient cohort is required to confirm the putative prognostic role of these candidate biomarkers. PMID- 26873139 TI - Impact of pitch angle setup error and setup error correction on dose distribution in volumetric modulated arc therapy for prostate cancer. AB - In volumetric modulated arc therapy (VMAT) for prostate cancer, a positional and rotational error correction is performed according to the position and angle of the prostate. The correction often involves body leaning, and there is concern regarding variation in the dose distribution. Our purpose in this study was to evaluate the impact of body pitch rotation on the dose distribution regarding VMAT. Treatment plans were obtained retrospectively from eight patients with prostate cancer. The body in the computed tomography images for the original VMAT plan was shifted to create VMAT plans with virtual pitch angle errors of +/-1.5 degrees and +/-3 degrees . Dose distributions for the tilted plans were recalculated with use of the same beam arrangement as that used for the original VMAT plan. The mean value of the maximum dose differences in the dose distributions between the original VMAT plan and the tilted plans was 2.98 +/- 0.96 %. The value of the homogeneity index for the planning target volume (PTV) had an increasing trend according to the pitch angle error, and the values of the D 95 for the PTV and D 2ml, V 50, V 60, and V 70 for the rectum had decreasing trends (p < 0.05). However, there was no correlation between differences in these indexes and the maximum dose difference. The pitch angle error caused by body leaning had little effect on the dose distribution; in contrast, the pitch angle correction reduced the effects of organ displacement and improved these indexes. Thus, the pitch angle setup error in VMAT for prostate cancer should be corrected. PMID- 26873140 TI - Usefulness of standardized uptake value normalized by individual CT-based lean body mass in application of PET response criteria in solid tumors (PERCIST). AB - Our aim in this study was to verify the usefulness of the standardized uptake value (SUV) normalized by individual CT-based lean body mass (LBMCT) in application of PET response criteria in solid tumors (PERCIST).We retrospectively investigated 14 patients (4 male and 10 female) with malignant lymphoma who were undergoing chemotherapy. (18)F-FDG PET/CT examinations were performed before and after chemotherapy. The LBMCT was calculated by estimation of fat weight from CT data (from skull base to pelvis). The mean +/- standard deviation (SD) and the Bland-Altman plot were used for comparison among body weight, LBMCT, and LBM derived from a predictive equation (LBMPE). Indices for FDG uptake in the liver were: SUV, SUV based on LBMPE (SULPE), and SUV based on LBMCT (SULCT). Overall differences between the uptake values were analyzed by one-way ANOVA. If the ANOVA showed significance, differences between uptake values were investigated further by use of the Tukey-Kramer test. The mean values of body weight, LBMPE, and LBMCT were: 55.4 +/- 14.9 (39.0-112.0), 43.0 +/- 10.5 (31.3-75.2), and 35.3 +/- 9.8 (23.4-75.8) kg, respectively. There was a wide dispersion between LBMPE and LBMCT (differences, 7.6 +/- 3.6 kg; 95 % CI, 6.42-8.85). LBMPE was higher than LBMCT in all the cases except in Case 11. The mean uptake values significantly differed among SUV, SULPE, and SULCT (F = 68.3, p < 0.05). Whereas SULPE deviated from PERCIST criteria in seven patients, SULCT satisfied the criteria except in one case. These results suggest that liver SULCT is useful for application of PERCIST. PMID- 26873141 TI - Perceived health concerns among sexual minority women in Mumbai, India: an exploratory qualitative study. AB - The experiences of sexual minority women (i.e., women who do not identify as 'heterosexual') in India have largely been absent in scientific literature. In partnership with India's oldest and largest sexual and gender minority-advocacy organisation, the Humsafar Trust, our study used community-based participatory research principles to explore the lived experiences and health concerns of sexual minority women in Mumbai. Study methodologies included interviews with key informants, a focus group comprised of six women, and an additional 12 in-person interviews with sexual minority women to identify important physical, mental, social and other health priorities from these women's perspectives. Thematic data are organised within the framework offered by the social ecological model, including individual, interpersonal, micro and macro levels. Findings from this study are important in providing the groundwork for future research and intervention involving sexual minority women in India, a dramatically underserved population. PMID- 26873142 TI - Clinical Evaluation of a Novel and Mobile Autism Risk Assessment. AB - The Mobile Autism Risk Assessment (MARA) is a new, electronically administered, 7 question autism spectrum disorder (ASD) screen to triage those at highest risk for ASD. Children 16 months-17 years (N = 222) were screened during their first visit in a developmental-behavioral pediatric clinic. MARA scores were compared to diagnosis from the clinical encounter. Participant median age was 5.8 years, 76.1 % were male, and most participants had an intelligence/developmental quotient score >85; 69 of the participants (31 %) received a clinical diagnosis of ASD. The sensitivity of the MARA in detecting ASD was 89.9 % [95 % CI = 82.7 97]; the specificity was 79.7 % [95 % CI = 73.4-86.1]. In a high-risk clinical setting, the MARA shows promise as a screen to distinguish ASD from other developmental/behavioral disorders. PMID- 26873144 TI - Results from the National Perinatal Patient Safety Program in Sweden: the challenge of evaluation. AB - INTRODUCTION: We studied the effects of the national Perinatal Patient Safety Program in Sweden, addressing local improvement measures, changes in the proportion of low Apgar score and the number of settled injury claims due to asphyxia. MATERIAL AND METHODS: Final reports on achieved improvements from all Swedish obstetric units were analyzed and categories of the improvement measures taken in perinatal risk areas were established. Data on all term newborns during 2006-12 were obtained from the Medical Birth Registry. Incidence of 5-min Apgar score <7 was analyzed before, during and after the intervention. The odds ratio for low Apgar score in period III vs. period I was calculated. Patient injury claims from The Swedish National Patient Insurance Company (LOF) were analyzed. RESULTS: Numerous local improvement initiatives were reported. The incidence of 5 min Apgar score <7 on a national level remained unchanged during the study periods. The units with the highest rate of Apgar score <7 showed a significant decrease in Apgar score of 4-6 after the intervention, whereas units with the lowest rate of Apgar score <7 showed a significant increase in Apgar score <7 after the intervention. A decline in settled claims due to substandard care was observed (7.5%, 2012-14; p for trend 0.049). CONCLUSION: The national incidence of low Apgar score remained unchanged but a reduction of settled claims of severely asphyxiated neonates was observed. The study highlights the need for robust designs when evaluating large-scale initiatives for improving patient safety at delivery, along with the difficulties in performing them. PMID- 26873143 TI - Severity of Autism Spectrum Disorders: Current Conceptualization, and Transition to DSM-5. AB - Mirroring the evolution of the conceptualization of autism has been changes in the diagnostic process, including the most recent revisions to the DSM-5 and the addition of severity-based diagnostic modifiers assigned on the basis of intensity of needed supports. A review of recent literature indicates that in research stratifying individuals on the basis of autism severity, core ASD symptomology is the primary consideration. This conceptualization is disparate from the conceptualization put forth in DSM-5 in which severity determination is based on level of needed support, which is also impacted by cognitive, language, behavioral, and adaptive functioning. This paper reviews literature in this area and discusses possible instruments that may be useful to inform clinical judgment in determining ASD severity levels. PMID- 26873146 TI - Corrigendum. PMID- 26873145 TI - MYC-induced apoptosis in mammary epithelial cells is associated with repression of lineage-specific gene signatures. AB - Apoptosis caused by deregulated MYC expression is a prototype example of intrinsic tumor suppression. However, it is still unclear how supraphysiological MYC expression levels engage specific sets of target genes to promote apoptosis. Recently, we demonstrated that repression of SRF target genes by MYC/MIZ1 complexes limits AKT-dependent survival signaling and contributes to apoptosis induction. Here we report that supraphysiological levels of MYC repress gene sets that include markers of basal-like breast cancer cells, but not luminal cancer cells, in a MIZ1-dependent manner. Furthermore, repressed genes are part of a conserved gene signature characterizing the basal subpopulation of both murine and human mammary gland. These repressed genes play a role in epithelium and mammary gland development and overlap with genes mediating cell adhesion and extracellular matrix organization. Strikingly, acute activation of oncogenic MYC in basal mammary epithelial cells is sufficient to induce luminal cell identity markers. We propose that supraphysiological MYC expression impacts on mammary epithelial cell identity by repressing lineage-specific target genes. Such abrupt cell identity switch could interfere with adhesion-dependent survival signaling and thus promote apoptosis in pre-malignant epithelial tissue. PMID- 26873147 TI - Prevalence of mitochondrial DNA mutations in sporadic patients with nonsyndromic sensorineural hearing loss. AB - INTRODUCTION: Several mitochondrial DNA mutations have been reported to be associated with nonsyndromic hearing loss in several families. However, little is known about the prevalence of these mutations in sporadic patients with nonsyndromic sensorineural hearing loss. OBJECTIVE: The purpose of our study was to investigate the incidence of these mitochondrial DNA mutations in such population. METHODS: A total of 178 sporadic patients with nonsyndromic sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral blood sample. We employed the SNaPshot((r)) sequencing method to detect five mitochondrial DNA mutations, including A1555G and A827G in 12S rRNA gene and A7445G, 7472insC, and T7511C in tRNA(Ser(UCN)) gene. Meanwhile, we used polymerase chain reaction and sequenced the products to screen GJB2 gene mutations in patients carrying mitochondrial DNA mutations. RESULTS: We failed to detect the presence of A1555G mutation in 12S rRNA gene, and of A7445G, 7472insC, T7511C mutations in tRNA(Ser(UCN)) gene in our population. However, we found that 6 patients (3.37%) were carriers of a homozygous A827G mutation and one of them also carried homozygous GJB2 235delC mutation. CONCLUSION: Our findings in the present study indicate that even in sporadic patients with nonsyndromic sensorineural hearing loss, mitochondrial DNA mutations might also contribute to the clinical phenotype. PMID- 26873148 TI - Intratympanic corticosteroid for sudden hearing loss: does it really work? AB - INTRODUCTION: Sudden deafness is characterized by an abrupt hearing loss of at least 30dB in three sequential frequencies in the standard pure tone audiogram over three days or less. Treatment is based on its etiology, and oral corticosteroids are widely used. Intratympanic corticosteroids are included as primary or secondary treatment when there is no improvement with the use of oral corticosteroids. OBJECTIVE: To determine the effectiveness of therapy with intratympanic steroids in sudden deafness. METHODS: A systematic review was performed of publications on the topic in the databases of PubMed/MEDLINE, with the keywords: sudden deafness, sudden hearing loss, and corticosteroids. RESULTS: Thirty scientific studies were analyzed. As to the objectives of the study analyzed, 76.7% sought to evaluate the use of intratympanic therapy salvage after failure to conventional treatment, and intratympanic therapy was used as the primary treatment 23.3% of the studies. CONCLUSION: Intratympanic corticosteroid therapy is prescribed primarily when there is failure of conventional therapy and when it is limited to use systemic corticosteroids, such as the diabetic patient. PMID- 26873149 TI - Capsule Commentary on Rana et al., Diabetes and Prior Coronary Heart Disease Are Not Necessarily Risk Equivalent for Future Coronary Heart Disease Events. PMID- 26873150 TI - The Relation Between Living Group Climate, Aggression, and Callous-Unemotional Traits in Delinquent Boys in Detention. AB - Aggression and callous-unemotional (CU) traits are common problems in incarcerated delinquent youth. The present study was conducted to examine whether living group climate was associated with aggression and CU traits in late adolescent male offenders ( N = 156) in a German youth prison. A structural equation model was fitted to the data and showed associations between repression and reactive aggression and CU traits, but no associations between an open and supportive living group climate and aggression and CU traits. Previous research in Dutch youth prisons did not find a relation between repression and aggression, buta relation between a positive living group climate and less aggression. These different findings may reflect differences in the German and Dutch prison system. Implications for practice are discussed. PMID- 26873152 TI - A Dynamic Risk Factors-Based Typology of Sexual Offenders. AB - The purpose of this article was to develop an Spanish psychometric typology of sexual offenders taking into account dynamic risk factors. The sample comprised 94 sex offenders imprisoned in Spain (52 rapists and 42 child molesters). The analysis yielded two different offender categories based on the subjects' criminogenic needs level (high and low). The results also showed that social desirability has a strong influence on the developed typologies, whereas the offence type, sociodemographic characteristics, and criminal history do not. A dynamic risk factors typology, such as the one proposed here, could help criminal and correctional facilities to fulfill their remit. It could also be useful for linking treatment intensity to offenders' criminogenic needs, as well as providing a platform for recidivism risk assessments. PMID- 26873153 TI - The diagnostic utility of labial salivary gland biopsy in IgG4-related disease. AB - OBJECTIVE: For the definitive diagnosis of IgG4-related disease (IgG4-RD), biopsies of local lesions are recommended so as to exclude other diseases, including lymphoma and cancer. However, performing biopsies of underlying organs is technically difficult. In this study, we examined the diagnostic utility of labial salivary gland (LSG) biopsy as a less invasive procedure. METHODS: Sixty six patients with suspected IgG4-RD by clinical findings or high serum IgG4 underwent LSG biopsy. We examined the relationship between the number of IgG4 positive plasma cells in LSG and clinical findings. RESULTS: The final diagnosis was 45 patients with IgG4-RD, 12 with Sjogren's syndrome, four with suspected Sjogren's syndrome, three with malignant lymphoma, one with systemic lupus erythematosus, and one with Warthin's tumor. The sensitivity, specificity, and accuracy of LSG biopsy were 55.6%, 100.0%, and 70.0%, respectively. Forty-five IgG4-RD patients were divided into two groups: 1) 25 with lesions of salivary glands (IgG4-RD S+) and 2) 20 without these lesions (IgG4-RD S-). Seventeen of 25 (68.0%) IgG4-RD S + and 8 of 20 (40.0%) IgG4-RD S - patients were positive for LSG biopsy. In the IgG4-RD S - patients, the mean number of affected organs and serum IgG4 in the positive cases for LSG biopsy were significantly higher than in the negative cases. CONCLUSION: A solo LSG biopsy is insufficient for the diagnosis of IgG4-RD because of its low sensitivity. However, LSG biopsy combined with clinical findings, including serum IgG4 and number of affected organs, may contribute towards a diagnosis of IgG4-RD patients with affected underlying organs. PMID- 26873156 TI - Body composition and energy and protein nutritional requirements for weight gain in Santa Ines crossbred sheep. AB - This study was conducted to evaluate the body composition and net energy and protein requirements for weight gain in Santa Ines crossbred sheep. Thirty woolless, 4-month-old, castrated male sheep with an initial body weight (BW) of 19.77 +/- 1.99 kg were used. Six animals (reference group) were slaughtered after the adaptation period to estimate empty body weight (EBW) and initial body composition. The remaining 24 animals were randomly distributed among four treatments (experimental diets) and slaughtered when they reached 30.24 +/- 0.78 kg BW. The body composition ranged from 162.88 to 160.4 g protein/kg EBW, from 59.49 to 164.23 g fat/kg EBW and from 1.54 to 2.46 Mcal energy/kg EBW for animals ranging between 20 and 30 kg BW. The net energy requirement for Santa Ines crossbred sheep linearly increased when BW increased from 20 to 30 kg. Within that same weight range, the net protein requirement for weight gain in sheep was constant, ranging from 12.61 to 12.42 g/day to 100 g daily weight gain. PMID- 26873157 TI - New approaches for morphological diagnosis of bovine Eimeria species: a study on a subtropical organic dairy farm in Brazil. AB - Bovine eimeriosis or coccidiosis is an intestinal disease caused by Eimeria spp. which is related to gastrointestinal disorders and, in some cases, death. The current work aimed to identify and provide detailed morphological characteristic features of the different Eimeria spp. parasites of crossbred cows of a subtropical organic dairy farm in Brazil, offering tools for the diagnosis of bovine eimeriosis. Eimeria auburnensis, Eimeria bovis, Eimeria bukidnonensis, Eimeria canadensis, Eimeria cylindrica, Eimeria ildefonsoi, and Eimeria zuernii were identified. The application of line regressions and ANOVA provided a means for the identification of these species. Finally, the current work proposes a dichotomous key to assist in the morphologic identification of bovine Eimeria spp. oocysts. PMID- 26873158 TI - Risk of Avalanche Involvement in Winter Backcountry Recreation: The Advantage of Small Groups. AB - OBJECTIVE: Avalanches are the primary hazard for winter backcountry recreationists and cause numerous deaths and injuries annually. Although recreationists usually travel in groups, there is little empirical knowledge on group-related risk factors. This study aims to explore the relative risk of avalanche accidents with respect to group size and to discuss underlying reasons for different risk levels. METHODS: We compared backcountry usage data in regions in Switzerland and Italy with avalanche accident data in these regions. RESULTS: We found higher avalanche risk for groups of 4 or more people and lower risk for people traveling alone and in groups of 2. The relative risk of group size 4, 5, and 6 was higher compared with the reference group size of 2 in the Swiss and Italian dataset. The relative risk for people traveling alone was not significantly different compared with the reference group size of 2 in the Italian dataset but was lower in the Swiss dataset. CONCLUSIONS: These findings are in accordance with avalanche safety recommendations regarding the higher risk of large groups but not regarding lower risks of people traveling alone in avalanche terrain, which is not recommended and requires great caution. Further studies on backcountry usage are necessary to improve our understanding of human behavior and risk factors. New techniques (eg, video monitoring) may be useful for acquiring reliable data on backcountry usage. PMID- 26873159 TI - Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis. AB - OBJECTIVE: To compare the effectiveness of three different biologics in anti Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA). METHODS: The study subjects were 110 biologics naive patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody negative patients. RESULTS: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-beta levels. CONCLUSIONS: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-beta levels, but not to TCZ and ABT. PMID- 26873160 TI - Mycoplasma genitalium: a possible case of macrolide resistance from Lebanon. PMID- 26873161 TI - Neurosyphilis: from infection to autoinflammation? PMID- 26873162 TI - Optimising physical activity engagement during youth sport: a self-determination theory approach. AB - Research suggests participation in youth sport does not guarantee physical activity (PA) guidelines are met. Studies indicate few children achieve recommended levels of moderate-to-vigorous physical activity (MVPA) during their youth sport involvement, and habitual levels of MVPA are below the recommended 60 min per day. Informed by self-determination theory, this study examined whether the coach-created social environment and related player motivation predict variability in objectively measured MVPA within the youth sport setting. Seventy three male youth sport footballers (Mean age = 11.66 +/- 1.62) completed a multisection questionnaire assessing their perceptions of the social environment created in youth sport (autonomy supportive and controlling) and motivation towards their football participation (autonomous and controlled). Intensity of PA during youth sport was measured using accelerometers (GT3X, ActiGraph). Results supported a model in which perceptions of autonomy support significantly and positively predicted autonomous motivation towards football, which in turn significantly and positively predicted youth sport MVPA (% time). A significant indirect effect was observed for perceptions of autonomy support on youth sport %MVPA via autonomous motivation. Results have implications for optimising MVPA engagement during youth sport and increasing daily MVPA towards recommended and health-enhancing levels on youth sport days. PMID- 26873163 TI - Informed consent: do information pamphlets improve post-operative risk-recall in patients undergoing total thyroidectomy: prospective randomized control study. AB - BACKGROUND: Informed consent consists of basic five elements: voluntarism, capacity, disclosure, understanding, and ultimate decision-making. Physician disclosure, patient understanding, and information retention are all essential in the doctor-patient relationship. This is inclusive of helping patients make and manage their decisions and expectations better and also to deal with any consequences and/or complications that arise. This study investigates whether giving patients procedure-specific handouts pre-operatively as part of the established informed consent process significantly improves overall risk-recall following surgery. These handouts outline the anticipated peri-operative risks and complications associated with total thyroidectomy, as well as the corrective measures to address complications. In addition, the influence of potential confounders affecting risk-recall, such as anxiety and pre-existing memory disturbance, are also examined. METHODS: Consecutive adult (>=18 years old) patients undergoing total thyroidectomy at a single academic tertiary care referral centre are included. Participants are randomly assigned into either the experimental group (with pamphlets) or the control group by a computerized randomization system (Clinstat). All participants filled out a Hospital Anxiety and Depression Scale (HADS) and they are tested by the physician for short-term memory loss using the Memory Impairment Screen (MIS) exam. All patients are evaluated at one week post-operatively. The written recall questionnaire test is also administered during this clinical encounter. RESULTS: Forty-nine patients are included--25 of them receive verbal consent only, while another 24 patients received both verbal consent and patient education information pamphlets. The overall average of correct answers for each group was 83% and 80% in the control and intervention groups, respectively, with no statistically significant differences. There are also no statistically significant differences between the two groups, in both interview duration, in time between interviews, and in recall tests. No correlation is also apparent between the pre-op HADS score and the recall questionnaire overall score. CONCLUSIONS: A pre-operative thyroid surgical information pamphlet alone might not be sufficient to enhance patient test scores and optimally educate the patient on their expected care pathway in thyroid surgery. Supplementation with alternative means of patient education perhaps using emerging technologies needs to be further investigated. PMID- 26873164 TI - Quality of life of patients with Diabetes Mellitus Types 1 and 2 from a referal health centre in Minas Gerais, Brazil. AB - Quality of life (QoL) characteristics are important in patients with diabetes mellitus (DM 1 and 2). AIM: Evaluate QoL and DM-associated factors among diabetic patients. METHODS: Patients attending a University Hospital were interviewed about their sociodemographic, clinical and QoL characteristics, with QoL measured via the EQ-5D. Descriptive analysis, correlation, linear regression, univariate and multivariate analysis were performed. RESULTS: 346 patients took part, comprising 67% women, 59% with DM2, and 32% DM1. DM 1 patients had a mean QoL score of 0.7369, with retinopathy, depression, dyslipidemia and a serious hypoglycemic crisis significantly reducing QoL. Patients with DM type 2 had a mean QoL score of 0.6582, with hypertension, neuropathy, depression, cancer and dyslipidemia significantly reducing QoL. Reduced QoL also correlated with a lack of physical exercise. Males with both DM1 and 2 had a better QoL than females. CONCLUSION: Need for better disease monitoring and control combined with effective activities to improve self-care, reduce complications and improve patients' QoL. PMID- 26873167 TI - Editorial. PMID- 26873165 TI - Use of Statins to Augment Progenitor Cell Function in Preclinical and Clinical Studies of Regenerative Therapy: a Systematic Review. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) are used in cell-based regenerative therapy. HMG CoA reductase inhibitors (statins) appear promising in blocking apoptosis, prolonging progenitor cell survival and improving their capacity to repair organ function. METHODS: We performed a systematic review of preclinical and clinical studies to clarify whether statins can improve cell-based repair of organ injury. MEDLINE, EMBASE, and PUBMED databases were searched (1947 to June 25, 2013). Controlled clinical and pre-clinical studies were included that evaluated statin therapy used alone or in combination with MSCs or EPCs in patients or animals with organ injury. RESULTS: After screening 771 citations, 100 records underwent full eligibility screening of which 38 studies met eligibility and were included in the review: Studies were grouped into pre-clinical studies that involved statin treatment in combination with cell therapy (18 studies), preclinical studies of statin therapy alone (13 studies) and clinical studies of statin therapy (7 studies). Studies addressed cardiac injury (14 studies), vascular disorders (15 studies), neurologic conditions (8 studies) and bone fractures (1 study). Pre-clinical studies of statins in combination with MSC infusion (15 studies) or EPC therapy (3 studies) were described and despite marked heterogeneity in reporting outcomes of cellular analysis and organ function, all of these cell-based pre-clinical studies reported improved organ recovery with the addition of statin therapy. Moreover, 13 pre-clinical studies involved the administration of a statin drug alone to animals. An increase in EPC number and/or function (no studies of MSCs) was reported in 11 of these studies (85 %) and improved organ function in 12 studies (92 %). We also identified 7 clinical studies and none involved the administration of cells but described an increased number and/or function of EPCs (no studies of MSCs) and improved organ function with statin therapy (1.2-fold to 35-fold improvement over controls) in all 7 studies. CONCLUSION: Our systematic review provides a foundation of encouraging results that support further study of statins in regenerative therapy to augment the number and/or function of MSCs used in cell-based repair and to augment the number and function of EPCs in vivo to repair damaged tissues. Larger studies are needed to ensure safety and confirm clinical benefits. PMID- 26873168 TI - Moises Broggi i Valles (1908-2012): Military surgeon and Catalan humanitarian. AB - Catalan surgeon Moises Broggi entered medical practice in 1931 as Spain was modernizing rapidly. Five years later, however, an attempted military coup sparked a nationwide civil war. Broggi offered his services to the embattled Republic and joined the Medical Service of the International Brigades. He served alongside colleagues from many countries, helping to develop advances in military medicine and especially trauma surgery. Broggi chose to remain working in Barcelona as Franco's Nationalist forces entered the city, in spite of the risk of reprisal he faced as a former officer of the International Brigades. Although forced from his leading position in the public health service, he developed a distinguished private practice. In the year of Franco's death he became President of Barcelona's Royal Academy of Medicine and he received many other honours. Just months before his death at the remarkable age of 104, Dr Moises Broggi continued to discuss and write about the concerns that had directed the course of his life- advances in medical science and the intellectual and political repression that had hindered delivery of those advances. In an article titled Exile and Silence he noted the groundbreaking work carried out under the auspices of the prestigious scientific institutions founded during Spain's Second Republic and the subsequent dark decades of exile suffered by many of their prominent scientists, some of them his close friends. PMID- 26873166 TI - Introduction of a polar core into the de novo designed protein Top7. AB - Design of polar interactions is a current challenge for protein design. The de novo designed protein Top7, like almost all designed proteins, has an entirely nonpolar core. Here we describe the replacing of a sizable fraction (5 residues) of this core with a designed polar hydrogen bond network. The polar core design is expressed at high levels in E. coli, has a folding free energy of 10 kcal/mol, and retains the multiphasic folding kinetics of the original Top7. The NMR structure of the design shows that conformations of three of the five residues, and the designed hydrogen bonds between them, are very close to those in the design model. The remaining two residues, which are more solvent exposed, sample a wide range of conformations in the NMR ensemble. These results show that hydrogen bond networks can be designed in protein cores, but also highlight challenges that need to be overcome when there is competition with solvent. PMID- 26873169 TI - Nathaniel Hodges (1629-1688): Plague doctor. AB - Nathaniel Hodges was the son of Thomas Hodges (1605-1672), an influential Anglican preacher and reformer with strong connections in the political life of Carolingian London. Educated at Westminster School, Trinity College Cambridge and Christ Church College, Oxford, Nathaniel established himself as a physician in Walbrook Ward in the City of London. Prominent as one of a handful of medical men who remained in London during the time of the Great Plague of 1665, he wrote the definitive work on the outbreak. His daily precautions against contracting the disease included fortifying himself with Theodore de Mayerne's antipestilential electuary and the liberal consumption of Sack. Hodges' approach to the treatment of plague victims was empathetic and based on the traditional Galenic method rather than Paracelsianism although he was pragmatic in the rejection of formulae and simples which he judged from experience to be ineffective. Besieged by financial problems in later life, his practice began to fail in the 1680s and he eventually died in a debtor's prison. PMID- 26873170 TI - Mansur ibn Ilyas (1380-1422 AD): A Persian anatomist and his book of anatomy, Tashrih-i Mansuri. AB - A Persian scholar, Mansur ibn Elyas, a late 14th century anatomist and physician from Shiraz, published his illustrated book on anatomy. Mansur's anatomy (Tashrih i Badan-i Insan) was written following the Mansur's medical synopsis, Kefaye Mojahedieh. The book of Mansur is believed to be the first anatomical illustrated manuscript containing two-dimensional pictures of the human body. This 14th century treatise is composed in Persian and is organized into five articles on the skeleton, nerves, muscles, veins and arteries, each illustrated with a full page diagram and with a final chapter including an image of a pregnant woman delivering a breech baby. These chapters have description part and related figure involving brief explanation. Mansur's illustrations were often used in other Persian or Arabic medical manuscripts for at least two centuries in Persia. PMID- 26873171 TI - Letter to the Editor. PMID- 26873173 TI - Insights on N-glycosylation of human haptoglobin and its association with cancers. AB - Protein glycosylation is one of the most significant post-translation modifications and plays a critical role in various biological functions. Haptoglobin (Hp) is one of the acute-phase response proteins secreted by liver. Its glycosylation could be analyzed by many analytical techniques qualitatively and quantitatively. The glycosylation alterations of Hp are reported to be associated with different kinds of diseases. The main glycosylation alterations of Hp in cancer appear to be the presence of aberrantly fucosylated and sialylated structures as well as increased branching. In this mini review, we provided a brief overview of Hp structure and biological function, discussed its glycosylation alterations in different cancers, and described the existing technologies for analyzing glycosylation site and glycan of Hp. Given the importance of Hp glycosylation, its unknown and unclear biological complexity and significances, Hp glycosylation has become a major target in cancer research. Development of sensitive and specific detection of Hp glycosylation including large-scale validation may be significant steps forward to its clinical application. PMID- 26873172 TI - Galectin-12 enhances inflammation by promoting M1 polarization of macrophages and reduces insulin sensitivity in adipocytes. AB - Galectin-12 is a member of an animal lectin family with affinity for beta galactosides and containing consensus amino acid sequences. Here, we found that galectin-12 was expressed in macrophages and thus aimed to determine how galectin 12 affects inflammation and macrophage polarization and activation. The ablation of galectin-12 did not affect bone marrow cells to differentiate into macrophages, but reduced phagocytic activity against Escherichia coli and lowered the secretion of nitric oxide. The ablation of galectin-12 also resulted in the polarization of macrophages into the M2 direction, as indicated by increases in the levels of M2 markers, namely, resistin-like beta (FIZZ1) and chitinase 3-like 3 (Ym1), as well as a reduction in the expression levels of a number of M1 pro inflammatory cytokines. We found that the diminished expression of pro inflammatory cytokines in macrophages resulting from galectin-12 deletion was due to reduced activation of IKKalpha/beta, Akt and ERK, which in turn caused decreased activation of NF-kappaB and activator protein 1. The activation of STAT3 was much higher in Gal12(-/-) macrophages activated by lipopolysaccharide, which was correlated with higher levels of IL-10. Adipocytes showed higher insulin sensitivity when treated with Gal12(-/-) macrophage-conditioned media than those treated with Gal12(+/+) macrophages. We conclude galectin-12 negatively regulates macrophage polarization into the M2 population, resulting in enhanced inflammatory responses and also in turn causing decreased insulin sensitivity in adipocytes. This has implications in the treatment of a wide spectrum of metabolic disorders. PMID- 26873175 TI - Detection of ALDH1 activity in rabbit hepatic VX2 tumors and isolation of ALDH1 positive cancer stem cells. AB - BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) activity has been implicated in the therapeutic drug resistance of many malignancies and has been widely used as a marker to identify stem-like cells, including in primary liver cancer. Cancer stem cells (CSCs) are thought to play a crucial role in cancer progression and metastasis. In order to clarify the validity of the rabbit VX2 liver cancer model, we questioned if it expresses ALDH1 as a potential marker of CSCs. Hepatocellular carcinoma is a common malignancy worldwide and has poor prognosis. Most of the animal models used to study hepatocellular carcinoma are rodent models which lack clinical relevance. The rabbit VX2 model is a large animal model useful for preclinical and for developing drugs targeting cancer stem cells. MATERIALS AND METHODS: We used flow cytometry to identify rabbit VX2 liver tumor cells that express ALDH1A1 activity at a high level and confirmed the results with RT-PCR, immunohistochemical and western blot analyses. Further, mRNA and protein expression analysis of tumor samples also express the markers for stemness like klf4, oct3/4, CD44 and nanog as well as the differentiation marker alpha-fetoprotein. RESULTS: We used Aldefluor flow cytometry-based assay to identify cells with high ALDH1 activity in the rabbit VX2 liver cancer model. We used the brightest 4.39 % of the total cancer cell population in our study. We performed semi-quantitative as well as real time PCR to characterize the stemness derived from VX2 tumors and tissues from normal rabbit liver. We demonstrated that VX2 tumors have higher expression of cancer stem cell markers such as AlDH1A1 and CD44 in comparison to normal rabbit liver cells. Additionally, real time PCR analysis of the same samples using syber-green demonstrated the significant change (p > 0.05) in the expression of genes. We validated the gene expression of the stemness markers by performing western blot and immunofluorescence. We showed that cancer stem cell markers (AlDH1A1, CD44) and the differentiation marker alpha-fetoprotein were upregulated in VX2 tumor cells. The same extent of upregulation was observed in stemness markers (klf4, oct3/4 and nanog) in VX2 tumors in comparison to normal rabbit liver. CONCLUSION: The overall results of this study indicate that ALDH1 is a valid CSC marker for VX2 cancer. This finding suggests that the rabbit VX2 liver cancer model is useful in studying drug resistance in hepatocellular carcinoma and may be useful for basic and preclinical studies of other types of human cancer. PMID- 26873176 TI - Investigating colloids and crystalloids--everything clear? PMID- 26873178 TI - Iron/folic acid supplementation during pregnancy prevents neonatal and under-five mortality in Pakistan: propensity score matched sample from two Pakistan Demographic and Health Surveys. AB - BACKGROUND: Several epidemiological studies from low- and middle-income countries have reported a protective effect of maternal antenatal iron/folic acid (IFA) on childhood mortality. OBJECTIVE: The current study aimed to evaluate the effect of maternal antenatal IFA supplementation on childhood mortality in Pakistan. DESIGN: A propensity score-matched sample of 8,512 infants live-born within the 5 years prior to interview was selected from the pooled data of two Pakistan Demographic and Health Surveys (2006/07 and 2012/13). The primary outcomes were childhood mortality indicators and the main exposure variable was maternal antenatal IFA supplementation. Post-matched analyses used Cox proportional hazards regression and adjusted for 16 potential confounders. RESULTS: Maternal antenatal IFA supplementation significantly reduced the adjusted risk of death on day 0 by 33% [adjusted hazard ratio (aHR)=0.67, 95% confidence interval (95% CI) 0.48-0.94], during the neonatal period by 29% (aHR=0.71, 95% CI 0.57-0.88), and for under-fives by 27% (aHR=0.73, 95% CI 0.60-0.89). When IFA was initiated in the first 4 months of pregnancy, the adjusted risk of neonatal and under-five deaths was significantly reduced by 35 and 33%, respectively. Twenty percent of under-five deaths were attributable to non-initiation of IFA in the first 4 months of pregnancy. With universal initiation of IFA in the first 4 months of pregnancy, 80,300 under-five deaths could be prevented annually in Pakistan. CONCLUSIONS: Maternal antenatal IFA supplementation significantly reduced neonatal and under-five deaths in Pakistan. Earlier initiation of supplements in pregnancy was associated with a greater prevention of neonatal and under-five deaths. PMID- 26873179 TI - Nocardia rayongensis sp. nov., isolated from Thai peat swamp forest soil. AB - An actinomycete strain, RY45-3T, isolated from a peat swamp forest soil in Rayong Province, Thailand, was characterized using a polyphasic approach. The strain belonged to the genus Nocardia on the basis of morphological, physiological, biochemical and chemotaxonomic properties. Cell-wall peptidoglycan contained meso diaminopimelic acid. The N-acyl group of muramic acid in the cell wall was glycolyl type. The diagnostic sugars in whole-cell hydrolysates were galactose and arabinose. MK-8 (H4omega-cycl) was the major menaquinone. The major fatty acids were C16 : 0 and C18 : 1omega9c. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. The genomic DNA G+C content was 71 mol%. On the basis of 16S rRNA gene sequence similarity analysis, strain RY45-3T was closely related to Nocardia jiangxiensis JCM 12861T (98.9 %), Nocardia nova JCM 6044T (98.8 %) and Nocardia pseudobrasiliensis JCM 9894T (98.6 %). The strain showed low levels of DNA-DNA relatedness with N. jiangxiensis JCM 12861T, N. nova JCM 6044T and N. pseudobrasiliensis JCM 9894T (range from 3.6 to 55.3 %). On the basis of the phenotypic characteristics and the results mentioned, this strain could be differentiated from closely related type strains and represents a novel species of the genus Nocardia, for which the name Nocardia rayongensis sp. nov. (type strain RY45-3T = JCM 19832T = TISTR 2213T = PCU 334T) is proposed. PMID- 26873177 TI - Perioperative management of diabetes in elective patients: a region-wide audit. AB - BACKGROUND: Ten percent of elective surgical patients have diabetes. These patients demonstrate excess perioperative morbidity and mortality. National guidance on the management of adults with diabetes undergoing surgery was published in 2011. We present a region-wide audit of adherence to this guidance across the North Western Deanery. METHODS: Local teams prospectively collected data according to a locally approved protocol. Pregnant, paediatric and non elective patients were excluded from this audit. Patient characteristics, type of surgery and aspects of perioperative management were collated and centrally analysed against audit criteria based upon national recommendations. RESULTS: 247 patients with diabetes were identified. HbA1c was recorded in 71% of patients preoperatively; 9% of patients with an abnormal HbA1c were not known by, or referred to, the diabetes team. 17% of patients were admitted the evening preceding surgery. The mean fasting time was 12:20(4) h. Variable rate i.v. insulin infusions (VRIII) were not used when indicated in 11%. Only 8% of patients received the recommended substrate fluid, along with the VRIII (5% glucose in 0.45% saline). Intra-operative capillary blood glucose (CBG) was measured hourly in 56% of patients. Intra-operative CBG was within the acceptable range (4-12 mmol.L(-1)) in 85% of patients. 73% of patients had a CBG measurement performed in recovery. The WHO checklist was used in 95% of patients. CONCLUSIONS: National perioperative guidelines were not adhered to in a substantial proportion of patients with diabetes undergoing elective surgery. This study represents a template for future trainee networks. PMID- 26873181 TI - Chip-based electrochromatography coupled to ESI-MS detection. AB - In this study, we present the coupling of chip-based electrochromatography to MS using a glass chip with a monolithically integrated nanoelectrospray emitter. As separation column, an acrylate-based porous polymer monolith is implemented into the glass chip by photopolymerization. For the establishment and development of this method, we used a test mixture detectable with both fluorescence and ESI-MS. After successful evaluation of the approach with the test solutes, it was applied exemplarily for drug analysis such as high-speed separations of benzodiazepines in pharmaceuticals. PMID- 26873180 TI - Risk and protective factors associated with being bullied on school property compared with cyberbullied. AB - BACKGROUND: We identified bullying victimization (bullied on school property versus cyberbullied) by selected demographic, personal characteristic, and behavior variables. METHODS: A cross-sectional analysis was conducted on adolescents (n = 13,583) completing the 2013 Youth Risk Behavior Survey (YRBS) in grades 9 through 12. RESULTS: Being bullied on school property in the past 12 months was significantly more common in females than males, in earlier school grades, and in Whites and other racial groups compared with Blacks and Hispanics. Being bullied on school property generally decreased with later school grades, but cyberbullying in the past 12 months remained constant. Being bullied on school property or cyberbullied was significantly positively associated with mental health problems, substance use, being overweight, playing video games for 3 or more hours per day, and having asthma. The association was greatest with having mental health problems. Cyberbullying was generally more strongly associated with these conditions and behaviors. Protective behaviors against bullying victimization included eating breakfast every day, being physically active, and playing on sports teams. Those experiencing victimization on school property and cyberbullying were significantly more likely to experience mental health problems compared with just one of these types of bullying or neither. CONCLUSIONS: Cyberbullying victimization is generally more strongly associated with mental health problems, substance use, being overweight, playing video games for 3 or more hours per day, and having asthma than bullying victimization on school property. However, because bullying on school property is more common in grades 9-11, this form of bullying has a greater burden on these conditions and behaviors in these school grades. PMID- 26873182 TI - Juvenile clinical predictors of clinical course and outcome in adult bipolar disorder. PMID- 26873183 TI - Swift and certain approaches to reduce alcohol reoffending. PMID- 26873184 TI - Can a criminal justice alcohol abstention programme with swift, certain, and modest sanctions (24/7 Sobriety) reduce population mortality? A retrospective observational study. AB - BACKGROUND: In the UK and USA, various jurisdictions have launched new approaches for managing alcohol-involved offenders that might have public health implications. These programmes require participants to abstain from alcohol and submit to frequent alcohol testing with swift, certain, and modest sanctions for violations, with the aim to reduce crime and keep alcohol-involved offenders in the community. In this study we examine whether the 24/7 Sobriety programme in South Dakota, USA-the largest such programme to date-is associated with reductions in mortality. METHODS: With a differences-in-differences design, we used variation in the timing of 24/7 Sobriety implementation across South Dakota counties between 2005 and 2011 to estimate the association between programme introduction and county-level mortality. We used monthly, county-level, aggregate counts for mortality from January, 2000, to June, 2011. We assessed total deaths, and deaths due to external injuries, circulatory disorders, digestive disorders, and cancer (as a potential placebo). FINDINGS: Between January, 2005, and June, 2011, 16 932 people (about 3% of the adult population) participated in the 24/7 Sobriety programme. The analysis was based on a sample size of 9 108 county-month observations (ie, 66 counties * 12 months * 11.5 years). Implementation of 24/7 Sobriety was associated with a 4.2% (95% CI 1.5-6.9) reduction in all-cause adult mortality, with the largest associations among women (8.0%, 95% CI 3.9-11.8) and individuals older than 40 years (4.3%, 95% CI 1.4-7.0). Associations were most evident among circulatory disorders. INTERPRETATION: 24/7 Sobriety might have public health benefits, which could extend beyond individuals directly enrolled in the programme. However, further research, including randomised controlled trials and analyses of individual-level data, is needed to corroborate the finding, reassess the size of these associations, and gain insight into causal mechanisms. Should a negative association be replicated, it might represent a substantial advance in our understanding of how criminal justice interventions could help shape public health. FUNDING: National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health. PMID- 26873185 TI - Childhood maltreatment and unfavourable clinical outcomes in bipolar disorder: a systematic review and meta-analysis. AB - BACKGROUND: Bipolar disorder affects up to one in 25 individuals and identification of early risk indicators of negative outcomes could facilitate early detection of patients with greatest clinical needs and risk. We aimed to investigate the association between childhood maltreatment and key negative outcomes in patients with bipolar disorder. METHODS: For this systematic review and meta-analysis we searched MEDLINE, PsycINFO, and Embase to identify articles published before Jan 1, 2015, examining the association of maltreatment (physical, sexual, or emotional abuse, neglect, or family conflict) before age 18 years with clinical features and course of illness in bipolar disorder. Data were extracted from published reports and any missing information was requested from investigators. We did 12 independent random-effects meta-analyses to quantify the associations between childhood maltreatment and course of illness or clinical features. FINDINGS: We initially identified 527 records and after unsuitable studies were removed, our search yielded 148 publications of which 30 were used in the meta-analysis. Patients with bipolar disorder and history of childhood maltreatment had greater mania severity (six studies, 780 participants; odds ratio [OR] 2.02, 95% CI 1.21-3.39, p=0.008), greater depression severity (eight studies, 1007 participants; 1.57, 1.25-1.99, p=0.0001), greater psychosis severity (seven studies, 1494 participants; 1.49, 1.10-2.04, p=0.011), higher risk of comorbidity with post-traumatic stress disorder (eight studies, 2494 participants; 3.60, 2.45-5.30, p<0.0001), anxiety disorders (seven studies, 5091 participants; 1.90, 1.39-2.61, p<0.0001), substance misuse disorders (11 studies, 5469 participants; 1.84, 1.41-2.39, p<0.0001), alcohol misuse disorder (eight studies, 5040 participants; 1.44, 1.13-1.83, p=0.003), earlier age of bipolar disorder onset (14 studies, 5733 participants; 1.85, 1.43-2.40, p<0.0001), higher risk of rapid cycling (eight studies, 3010 participants; 1.89, 1.45-2.48, p<0.0001), greater number of manic episodes (seven studies, 3909 participants; 1.26, 1.09-1.47, p=0.003), greater number of depressive episodes (eight studies, 4025 participants; 1.38, 1.07-1.79, p=0.013), and higher risk of suicide attempt (13 studies, 3422 participants; 2.25, 1.88-2.70, p<0.0001) compared with those with bipolar disorder without childhood maltreatment. Overall, these associations were not explained by publication bias, undue effects of individual studies, or variation in study quality. INTERPRETATION: Childhood maltreatment predicts unfavourable clinical features and course of illness in patients with bipolar disorder. FUNDING: None. PMID- 26873186 TI - Computational Drug Repositioning by Target Hopping: A Use Case in Chagas Disease. AB - BACKGROUND: Drug repositioning aims to identify novel indications for existing drugs. One approach to repositioning exploits shared binding sites between the drug targets and other proteins. Here, we review the principle and algorithms of such target hopping and illustrate them in Chagas disease, an in Latin America widely spread, but neglected disease. CONCLUSION: We demonstrate how target hopping recovers known treatments for Chagas disease and predicts novel drugs, such as the antiviral foscarnet, which we predict to target Farnesyl Pyrophosphate Synthase in Trypanosoma cruzi, the causative agent of Chagas disease. PMID- 26873187 TI - Synthesis, Cytotoxic Evaluation, Docking and QSAR Study of N-(4-Oxo- 2-(4-((5 Aryl-1,3,4-Thiadiazol-2-yl)Amino)Phenyl)Thiazolidin-3-yl) Benzamides as Antitubulin Agents. AB - In the present study an efficient strategy for the synthesis of thiazole and thiadiazole derivatives was developed and clubbed together both of the substituted nucleus to form the analogues of combretastatin A-4 (tubulin polymerization inhibitors.). Synthesis was started by the reaction of substituted benzoic acid with thionyl chloride followed by the reaction with hydrazine, p chloro benzaldehyde and thioglycolic acid to form substituted thiazole derivatives. On the other side hydrazides were reacted with ammonium thiocyanate and strong acid to form substituted thiadiazole compounds. Finally thiazole and thiadiazole compounds were clubbed with the help of dioxan and triethylamine. All novel derivatives (TH01-TH40) were screened for their cytotoxicity activity using MTT assay against three cancer cell lines viz. A-549 (lung carcinoma), HT-29 (colon carcinoma), HeLa (cervix carcinoma). Compounds TH08 exhibited highest activity, due to the presence of trimethoxy substitution on phenyl ring. In QSAR study these results were correlated with physicochemical parameters and the correlation of XlogP, kaapa2, Quadrupole1 with cytotoxic activity on A-549 (lung carcinoma) was found highest (r2: 0.941; F: 99.103; Se: 0.0006). In docking study binding of active molecule (TH08) was found very well with alpha, beta tubulin (PDB: 1SA0) protein. PMID- 26873188 TI - P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design. AB - A major impediment for cancer chemotherapy is the development of multidrug resistance (MDR). Continuous use of chemotherapeutic drugs during cancer therapy induces the expression of PGlycoprotein (P-gp, MDR1), an ATP dependant transporter, which in turn reduces the intracellular accumulation of chemotherapeutic drugs leading to MDR. Extensive research over the years has identified several potential P-gp inhibitors, both synthetic as well as natural origin, to overcome the MDR during cancer chemotherapy. In this review, we discuss the cellular pathways involved and transcription factors regulating the expression of P-gp. A number of phytochemicals are reported to inhibit P-gp activity and MDR1 expression; the structure-activity relationship (SAR) among the phytochemicals for P-gp inhibition and the effect of these phytochemicals on cellular signaling pathways regulating P-gp expression are discussed in detail. Moreover, structural biology and mutagenesis studies on P-gp along with docking studies throw light on the structural requirements for P-gp inhibition. Insight provided in the review about the phytochemicals molecular mechanism and SAR could catalyze the design of potent P-gp inhibitors in the future and could help to overcome MDR in cancer chemotherapy. PMID- 26873189 TI - Oleuropein Mediated Targeting of Signaling Network in Cancer. AB - Cancer is a multifaceted and genomically complex disease. Rapidly accumulating preclinical and clinical studies are emphasizing on wide ranging molecular mechanisms that underpin cancer development, progression and metastasis. Intratumor heterogeneity, loss of apoptosis, rapidly developing resistance against molecular therapeutics and off-target effects are some of the deeply studied resistance mechanisms. Data obtained through high-throughput technologies has considerably enhanced our understanding of the intracellular signaling cascades frequently dysregulated spatio-temporally. There is an ever-expanding list of synthetic and natural agents reported to activate tumor suppressor genes and inhibit oncogenes in cancer cells. Markedly reduced tumor growth has also been documented in xenografted mice administered with phytochemicals. Oleuropein is a bioactive ingredient isolated from various sources and there is evidence of complete regression of tumors in 9- 12 days in mice orally administered with Oleuropein. In this review we summarize recent developments in use of Oleuropein as an anticancer agent. Extraction and isolation of Oleuropein and how it modulates intracellular signaling network to induce apoptosis in cancer cells. Human epidermal growth factor receptor 2 (HER2) frequently overexpressed in breast cancer cells is inhibited by Oleuropein. Interestingly, trastuzumab efficacy was notably enhanced in Oleuropein treated breast cancer cells. There is still insufficient information related to Oleuropein mediated microRNA regulation in cancer cells. We still do not have information about regulation of different signaling cascades by Oleuropein which are deregulated in cancer. Future studies must converge on a deeper analysis of target molecular network of Oleuropein and its efficacy as a tumor growth inhibitor in xenografted mice. PMID- 26873190 TI - Kisspeptin Mediated Signaling in Cancer. AB - Research over the years has gradually and sequentially highlighted contributory role of hypothalamic- based kisspeptin-signaling axis as a major positive modulator of the neuroendocrinological reproductive axis in mammals. However, a series of landmark studies provided convincing evidence of role of this signaling in regulation of cancer development and progression. It is becoming progressively more understandable that loss or reduction of KISS1 expression in different human cancers correlates inversely with progression of tumor, metastasizing potential and survival. In this review we have attempted to provide an overview highlight of the most recent updates addressing metastasis- suppressing role of KISS1. We also summarize interplay of microRNA and KISS1 in cancer. The miRNA regulation of different genes is a rapidly expanding area of research however, the community lacks a deep understanding of miRNA regulation of KISS1. Recently, emerging laboratory findings have shown that KISS1 is transcriptionally controlled by TCF21 that is in turn regulated by miR-21. Therefore, there is an urgent need for further study of how miRNA directly or indirectly influences KISS1 at the posttranscriptional level. There is also a lack of evidence regarding natural agents that mediate upregulation or downregulation of KISS1. Increasing the knowledge of the KISS1/KISS1R signaling axis will be helpful in achieving personalized medicine. PMID- 26873191 TI - Nitroxyl (HNO): A Possible Strategy for Fighting Cancer. AB - Nitroxyl (HNO), the one electron reduced form of nitric oxide (NO), shows a very distinct chemistry and biology from that of NO. Chemical profile is characterized by reactions with thiols and thiol proteins such as aldehyde dehydrogenase, glyceraldehyde 3-phosphate dehydrogenase, caspases among others. Biological profile of HNO includes cardioprotective actions especially in cases of heart failure. This short review focuses on the cytotoxic properties for HNO. Nitroxyl was found to be toxic to several cancer cell lines including lung and breast cancers. Critical thiols that control cancer cellular functions might be the target for HNO activity. The anti-tumor actions of HNO donating aspirin is also summarized. PMID- 26873192 TI - Artesunate as an Anti-Cancer Agent Targets Stat-3 and Favorably Suppresses Hepatocellular Carcinoma. AB - BACKGROUND: Aberrant signal transducer and activator of transcription 3 (STAT-3) molecular signaling elicit hepatocellular carcinoma (HCC) in humans. Therefore, targeting STAT-3 is considered as an attractive option towards suppression of HCC in humans. OBJECTIVE: Our objective is to identify a potential small molecule inhibitor that can specifically target STAT-3 and suppress HCC. METHODS: In this study, we analyze a group of sesquiterpene lactone (STL) candidates that has been recently reported in preclinical trials against cancer by a unified computational and experimental approach. RESULTS: Our virtual analysis of the STL candidates revealed Artesunate (ATS) as the best potential inhibitor of STAT-3 with comparable potency to specific inhibitor S3I-201. We also observed that ATS inhibited IL-6 driven STAT-3-DNA binding activity with comparable potency to S3I 201 in a cell free system. Furthermore ATS was observed to interfere with STAT-3 dimerization and suppression of both constitutive and IL-6 inducible STAT-3 in vitro. Nevertheless, we also observed that ATS modulated STAT-3 dependent targets (procaspase-3, Bcl-xl and survivin) favoring occurrence of apoptosis in vitro. Overall, the putative inhibition of STAT-3 by ATS suggested its capacity to interfere with STAT-3 dimerization by binding to the SH2 domain of STAT-3 monomer. It resulted in suppression of STAT-3 and also favored promotion of in vitro cells towards apoptosis. Consequently, ATS also exhibited selective cytotoxicity of cancer cells over normal cells in vitro. CONCLUSION: All the above observations substantiated by unified computational and in vitro experimental approaches suggested its potential role as a therapeutic anti-cancer agent against HCC. PMID- 26873193 TI - Novel Approaches Towards Designing of Isoform-Selective Inhibitors Against Class II Histone Deacetylases: The Acute Requirement for Targetted Anticancer Therapy. AB - Histone deacetylases (HDACs) regulate gene expression by modulating chromatin architecture via histone hypoacetylation. They play a key role in regulating cellular processes including cell cycle arrest and apoptosis. Hyperactivity of HDACs plays a key role in tumour onset and progression making these enzymes as striking targets for anticancer drugs and therapy. Certain cancers are associated with upregulation of specific class II HDAC isoform rather than multiple ones. Therapeutic intervention using small-molecules namely histone deacetylase inhibitors (HDACi), often targets many isoforms unselectively (pan-HDACi) due to structural identity culminating in debilitating off-target effects and reduced in vivo potency. This emphasizes the escalating need for developing isoform selective inhibitors against the defined class of HDACs. Despite the safe and elevated therapeutic benefit, the design of such inhibitors has been challenging. The present article provides intricate details about the role of class II HDAC isoforms in fuelling distinct cancers and the current challenges with the use of pan-HDAC inhibitors in anticancer therapy. The article also highlights the diverse synthetic and in silico approaches taken by scientific community towards the designing of isoform-selective inhibitors against class II HDAC isoforms. The strategies discussed in this review will provide further impetus to the ongoing research regarding the designing of isoform-selective inhibitors for safe and effective anticancer therapy which is today's need. PMID- 26873195 TI - Development of magnetic molecularly imprinted polymers for selective extraction: determination of citrinin in rice samples by liquid chromatography with UV diode array detection. AB - In this work, we report the synthesis of novel magnetic molecularly imprinted polymers (m-MIPs) and their application to the selective extraction of the mycotoxin citrinin (CIT) from food samples. The polymers were prepared by surface imprinting of Fe3O4 nanoparticles, using 2-naphtholic acid (2-NA) as template molecule, N-3,5-bis(trifluoromethyl)phenyl-N'-4-vinylphenyl urea and methacrylamide as functional monomers and ethyleneglycol dimethacrylate as cross linker. The resulting material was characterized by transmission electron microscopy (TEM), and X-ray diffraction (XRD) and Fourier transform infrared spectroscopies (FT-IR). The polymers were used to develop a solid-phase extraction method (m-MISPE) for the selective recovery of CIT from rice extracts prior to its determination by HPLC with UV diode array detection. The method involves ultrasound-assisted extraction of the mycotoxin from rice samples with (7:3, v/v) methanol/water, followed by sample cleanup and preconcentration with m MIP. The extraction (washing and elution) conditions were optimized and their optimal values found to provide CIT recoveries of 94-98 % with relative standard deviations (RSD) less than 3.4 % (n = 3) for preconcentrated sample extracts (5 mL) fortified with the analyte at concentrations over the range 25-100 MUg kg( 1). Based on the results, the application of the m-MIPs facilitates the accurate and efficient determination of CIT in rice extracts. PMID- 26873194 TI - Telomerase as a Cancer Target. Development of New Molecules. AB - Telomeres are the terminal part of the chromosome containing a long repetitive and noncodifying sequence that has as function protecting the chromosomes. In normal cells, telomeres lost part of such repetitive sequence in each mitosis, until telomeres reach a critical point, triggering at that time senescence and cell death. However, in most of tumor cells in each cell division a part of the telomere is lost, however the appearance of an enzyme called telomerase synthetize the segment that just has been lost, therefore conferring to tumor cells the immortality hallmark. Telomerase is significantly overexpressed in 80 95% of all malignant tumors, being present at low levels in few normal cells, mostly stem cells. Due to these characteristics, telomerase has become an attractive target for new and more effective anticancer agents. The capability of inhibiting telomerase in tumor cells should lead to telomere shortening, senescence and apoptosis. In this work, we analyze the different strategies for telomerase inhibition, either in development, preclinical or clinical stages taking into account their strong points and their caveats. We covered strategies such as nucleosides analogs, oligonucleotides, small molecule inhibitors, G quadruplex stabilizers, immunotherapy, gene therapy, molecules that affect the telomere/ telomerase associated proteins, agents from microbial sources, among others, providing a balanced evaluation of the status of the inhibitors of this powerful target together with an analysis of the challenges ahead. PMID- 26873197 TI - The development and comparison of collection techniques for inorganic and organic gunshot residues. AB - The detection and interpretation of gunshot residues (GSR) plays an important role in the investigation of firearm-related events. Commonly, the analysis focuses on inorganic particles incorporating elements derived from the primer. However, recent changes in ammunition formulations and possibility that particles from non-firearm sources can be indistinguishable from certain primer particles challenge the standard operational protocol and call for adjustments, namely the combination of inorganic and organic GSR analysis. Two protocols for the combined collection and subsequent analysis of inorganic and organic GSR were developed and optimised for 15 compounds potentially present in organic GSR (OGSR). These protocols were conceptualised to enable OGSR analysis by ultrahigh-performance liquid chromatography (UHPLC) coupled with UV detection and triple quadrupole tandem mass spectrometry (confirmation) and IGSR analysis by scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDX). Using liquid extraction, the extraction recoveries from spiked swabs and stubs were ~80 % (50-98 % for swabs, 64-98 % for stubs). When the mixed OGSR standard was applied to the hands and recovered in the way that is usual for IGSR collection, GSR stubs performed significantly better than swabs (~30 %) for the collection of OGSR. The optimised protocols were tested and compared for combined OGSR and inorganic GSR analysis using samples taken at a shooting range. The most suitable protocol for combined collection and analysis of IGSR and OGSR involved collection using GSR stubs followed by SEM-EDX analysis and liquid extraction using acetone followed by analysis with UHPLC. PMID- 26873199 TI - Target-based metabolomics for the quantitative measurement of 37 pathway metabolites in rat brain and serum using hydrophilic interaction ultra-high performance liquid chromatography-tandem mass spectrometry. AB - Amino acids, neurotransmitters, purines, and pyrimidines are bioactive molecules that play fundamental roles in maintaining various physiological functions. Their metabolism is closely related to the health, growth, development, reproduction, and homeostasis of organisms. Most recently, comprehensive measurements of these metabolites have shown their potential as innovative approaches in disease surveillance or drug intervention. However, simultaneous measurement of these metabolites presents great difficulties. Here, we report a novel quantitative method that uses hydrophilic interaction ultra-high-performance liquid chromatography-tandem mass spectrometry (HILIC-UPLC-MS/MS), which is highly selective, high throughput, and exhibits better chromatographic behavior than existing methods. The developed method enabled the rapid quantification of 37 metabolites, spanning amino acids, neurotransmitters, purines, and pyrimidines pathways, within 6.5 min. The compounds were separated on an ACQUITY UPLC(r) BEH Amide column. Serum and brain homogenate were extracted by protein precipitation. The intra- and interday precision of all of the analytes was less than 11.34 %, and the accuracy was between -11.74 and 11.51 % for all quality control (QC) levels. The extraction recoveries of serum ranged from 84.58 % to 116.43 % and those of brain samples from 80.80 % to 119.39 %, while the RSD was 14.61 % or less for all recoveries. This method was used to successfully characterize alterations in the rat brain and, in particular, their dynamics in serum. The following study was performed to simultaneously test global changes of these metabolites in a serotonin antagonist p-chlorophenylalanine (PCPA)-induced anxiety and insomnia rat model to understand the effect and mechanism of PCPA. Taken together, these results show that the method is able to simultaneously monitor a large panel of metabolites and that this protocol may represent a metabolomic method to diagnose toxicological and pathophysiological states. PMID- 26873198 TI - Simultaneous determination of urinary parabens, bisphenol A, triclosan, and 8 hydroxy-2'-deoxyguanosine by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. AB - A simple and fast method was developed for the simultaneous determination of five parabens, bisphenol A (BPA), triclosan (TCS), and 8-hydroxy-2'-deoxyguanosine (8 OHdG) in human urine using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The solid-phase extraction (SPE) procedure, chromatographic conditions, and MS/MS parameters were optimized to achieve maximum sensitivity and accuracy for the analytes. The validation results showed that the correlation coefficients (R (2)) and recoveries ranged from 0.999 to 1 and 83.9 to 109.9 %, respectively, and the intra-day and inter day precisions (relative standard deviation, RSD) were within the range of 1.3 8.5 % and 1.3-9.0 %, respectively. The limits of detection for the analytes ranged from 0.001 to 0.05 MUg/L. The method was successfully employed to determine parabens, BPA, TCS, and 8-OHdG in urine samples from school students in Guangzhou, China. The results showed that methyl, ethyl, n-propyl parabens, BPA, TCS, and 8-OHdG were frequently detected in urine samples. n-Butyl and benzyl parabens were only detected in a part of the samples due to their low concentrations in urine. PMID- 26873202 TI - Erratum to: Ultrasensitive determination of bisphenol A and its chlorinated derivatives in urine using a high-throughput UPLC-MS/MS method. PMID- 26873200 TI - Rapid evaluation of artesunate quality with a specific monoclonal antibody-based lateral flow dipstick. AB - Artesunate is a frontline antimalarial drug for treating Plasmodium falciparum malaria. To produce specific antibodies to artesunate, the carboxyl group of artesunate was directly conjugated to carrier protein as the immunogen. A specific monoclonal antibody (mAb) 3D82G6 against artesunate was obtained by high throughput screening of positive hybridoma clones. This monoclonal antibody had 4.0, 0.5, and 0.9 % cross reactivities with artemisinin, dihydroartemisinin, and artemether, respectively. A dipstick immunoassay was developed, and the indicator range for artesunate was 1000-2000 ng mL(-1). No interference was observed with artemisinin, dihydroartemisinin, artemether, and other commonly used antimalarial drugs for up to 20,000 ng mL(-1). The dipsticks were used for determination of artesunate contents in commercial drugs, and the results were agreeable with those determined by high-performance liquid chromatography. This dipstick, with its specificity and sensitivity for artesunate and simplicity to use, makes it a potential point-of-care device for rapid quality evaluation of artesunate containing antimalarial drugs. Graphical Abstract Specific monoclonal antibody based lateral flow dipstick for artesunate. PMID- 26873203 TI - Analysis of cocaine and metabolites in hair: validation and application of measurement of hydroxycocaine metabolites as evidence of cocaine ingestion. AB - An LC/MS/MS method to identify and quantitate in hair the minor metabolites of cocaine-meta-, para-, and ortho-hydroxy cocaine-was developed and validated. Analysis was performed on a triple quadrupole ABSciex API 3000 MS equipped with an atmospheric pressure ionization source via an IonSpray (ESI). For LC, a series 200 micro binary pump with a Perkin Elmer Model 200 autosampler was used. The limit of detection (LOD) and limit of quantification (LOQ) were 0.02 ng/10 mg hair, with linearity from 0.02 to 10 ng/10 mg hair. Concentrations of the para isomer in extensively washed hair samples were in the range of 1-2 % of the cocaine in the sample, while the concentrations of the ortho form were considerably less. The method was used to analyze large numbers of samples from two populations: workplace and criminal justice. In vitro experiments to determine if deodorants or peroxide-containing cosmetic treatments could result in the presence of these metabolites in hair showed that this does not occur with extensively washed hair. Presence of hydroxycocaines, when detected after aggressive washing of the hair samples, provides a valuable additional indicator of ingestion of cocaine rather than mere environmental exposure. PMID- 26873204 TI - A novel, simultaneous extraction of FAEE and EtG from meconium and analysis by LC MS/MS. AB - Fatty acid ethyl esters (FAEEs) and ethyl-glucuronide (EtG) in meconium have been widely studied as biomarkers of maternal alcohol consumption during pregnancy. Many analytical approaches have been proposed for their analysis, mostly consisting of separated extraction procedures requiring the use of two meconium aliquots. This study aimed to validate a new analytical procedure for the simultaneous extraction of FAEEs and EtG from a meconium aliquot through a single solid-phase extraction (SPE) applied to 242 anonymized samples of meconium. Targeted FAEEs were: ethyl-myristate (Myr), ethyl-palmitate (Pal), ethyl-oleate (Ole) and ethyl-stearate (Ste). Two hundred milligrams of meconium was sonicated with acetonitrile, and a single SPE performed by means of aminopropyl columns. FAEEs were eluted with hexane, followed by EtG elution with water. Both the mixtures were dried, recovered, and analyzed by liquid chromatography-tandem mass spectrometry using C8 (FAEEs) and C18 (EtG) columns. Transitions were: m/z 257 -> 57,88, Myr; m/z 262 -> 57,88, Myr-d5; m/z 285 -> 57, 72, Pal; m/z 290 -> 57,258, Pal-d5; m/z 311 -> 72,114, Ole; m/z 316 -> 72,265, Ole-d5; m/z 257 -> 57,72 Ste; m/z 318 -> 57,286, Ste-d5; m/z 221 -> 75,85, EtG; m/z 226 -> 75,85, EtG-d5. Lower limit of quantification range was 10-15 ng/g for FAEEs and 10 ng/g for EtG. Linearity was evaluated for different concentration ranges; the mean coefficients of determination (R (2)) were above 0.9961. Precision and accuracy for FAEEs and EtG were consistently <=20 % and +/-20 %, respectively. Ion suppression was observed for all the analytes. Matrix effect did not significantly affect the analyses. Recovery efficiency was 93 % for EtG and 75-85 % for FAEEs. PMID- 26873206 TI - Erratum to: Development of redox-sensitive red fluorescent proteins for imaging redox dynamics in cellular compartments. PMID- 26873205 TI - Identification and determination of ergot alkaloids in Morning Glory cultivars. AB - Seeds of plants from Ipomoea genera contain numerous ergot alkaloids, including psychoactive ergine and ergometrine, and are often abused as so-called "legal highs." In this work, an analytical method for determination of ergine and ergometrine, and identification of other alkaloids was developed, optimized, and validated. Three extraction techniques, ultrasound-assisted extraction in bath, or with sonotrode, and microwave-assisted extraction were evaluated, and it was concluded that ultrasonic bath is the most suitable technique for extraction of ergot alkaloids. The extraction method was later optimized using a Doehlert experimental design with response surface methodology and used together with the optimized LC-Q-TOF-MS method. The analytical procedure was validated in terms of recovery and matrix effect, repeatability, and intermediate precision. Limits of detection and quantification were 1.0 and 3.0 ng mL(-1), respectively, and were sufficient for determination of ergot alkaloids in Ipomoea seeds. The analysis revealed that from five kinds of seeds purchased from different vendors, only three contained ergot alkaloids. Concentration of alkaloids and their relative abundance was similar in samples representative for whole seeds packs; however, when single seeds were analyzed, significant discrepancies in ergine and ergometrine concentrations were detected. PMID- 26873207 TI - Silver nanoparticle-modified electrode for the determination of nitro compound containing pesticides. AB - This paper reports the electroanalytical determination of pendimethalin and ethyl parathion by square-wave adsorptive stripping voltammetry using a material comprised of chitosan-stabilized silver nanoparticles to modify a glassy carbon electrode. Under optimized experimental conditions, the peak current was found to vary linearly with the concentration of pendimethalin in the range of 70 to 2000 nmol L(-1) and with concentration of ethyl parathion in the range of 40 to 8000 nmol L(-1). Detection limits of 36 and 40 nmol L(-1) were obtained for pendimethalin and ethyl parathion, respectively. The silver - nanoparticle modified electrode was successfully employed for the analysis of pesticides in tap and mineral water (pendimethalin) and in lettuce and honey (ethyl parathion) samples. Pendimethalin recovery was between 94 and 100 %, and ethyl parathion recovery was between 97 and 101 %, indicating no significant matrix interference effects on the analytical results. The accuracy of the electroanalytical methodology using the proposed modified electrode was also compared to that of the UV-vis spectrophotometric method. PMID- 26873208 TI - The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods. AB - Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF beta1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite." PMID- 26873210 TI - In situ monitoring, separation, and characterization of gold nanorod transformation during seed-mediated synthesis. AB - The control of gold nanorod (GNR) solution-based syntheses has been hindered in part by the inability to examine and control the conversion of precursor seed populations to anisotropic materials, which have resulted in low yields of desired products and limited their commercial viability. The advantages offered by tandem separation and characterization methods utilizing asymmetric-flow field flow fractionation (A4F) are principally achieved as a result of their non disruptive nature (minimizing artefacts), fast throughput, and in-situ analysis. With hyphenated A4F methods, resolved populations of seeds and secondary products, up to long aspect ratio rods, have been achieved and exemplify progress towards elucidating mechanistic aspects of formation and thus rational design. While there have been previously reported studies on A4F separation of GNRs, to our knowledge, this is the first published investigation of in situ GNR growth, separation, and characterization based on A4F, where its utilization in this capacity goes beyond traditional separation analysis. By using hydroquinone as the reducing agent, the conversion of the initial seed population to a distribution of products, including the GNRs, could be monitored in real time using A4F hyphenated with a diode array detector. Transmission electron microscopy confirms that the number of peaks observed during fractionation corresponds with size and shape dispersity. This proof-of-principle study introduces A4F as a technique that establishes a foundation for future mechanistic studies on the growth of GNRs from gold seeds, including conversion of the seed population to initial products, a topic highly relevant to advancing progress in nanomanufacturing. PMID- 26873211 TI - Catalytic chemiluminescent detection of cholesterol in serum with Cu2-x Se semiconductor nanoparticles. AB - It is very important to be able to accurately and rapidly measure the cholesterol level in the human body, as cholesterol is associated with various diseases, such as Alzheimer's disease. In this work, a novel method of detecting cholesterol using chemiluminescence (CL) based on a newly prepared semiconductor catalyst, Cu2-x Se nanoparticles (Cu2-x Se NPs), was developed. It was found that the Cu2-x Se NPs strongly enhanced the CL signal by producing a large number of reactive oxygen species (ROS) in the luminol-Cu2-x Se NPs system. Based on the UV-vis-NIR absorption spectra, zeta potential, CL spectrum, and an investigation of the ROS, a possible mechanism for the CL was proposed. This CL-based method was successfully applied to determine cholesterol. It was found that the enhanced CL was proportional to the concentration of cholesterol over the range of 82 nM to 1.96 MUM with a detection limit of 0.062 nM, and that added cholesterol was successfully detected in human serum with a mean recovery of 97 %. PMID- 26873212 TI - Electrochemically oxidized multiwalled carbon nanotube/glassy carbon electrode as a probe for simultaneous determination of dopamine and doxorubicin in biological samples. AB - A facile and effective approach of fabricating oxidized multiwalled carbon nanotube/glassy carbon electrode (OMWCNT/GCE) is herein reported. The OMWCNT/GCE was prepared by electrochemical oxidation method in basic media (0.5 mol L(-1) NaOH solution) and used as a sensor for simultaneous determination of dopamine (DA) and doxorubicin (DOX). Scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry were used for characterization and performance study of the OMWCNT/GCE. The modified electrode exhibited good electrocatalytic properties toward the oxidation of DA and DOX. Peaks potential difference of 240 mV between DA and DOX was large enough to determine DA and DOX individually and simultaneously. Square wave voltammetry (SWV) was used for the simultaneous determination of DA and DOX in their binary mixture. Under the optimum conditions, the linear concentration dependences of SW peak current responses were observed for DA and DOX in the concentration ranges of 0.03-55 MUmol L(-1) and 0.04-90 MUmol L(-1), respectively. The detection limits (S/N = 3) were 8.5 * 10(-3) MUmol L(-1), and 9.4 * 10(-3) MUmol L(-1) for DA and DOX, respectively. The analytical utility of OMWCNT/GCE was also successfully demonstrated for the simultaneous determination of DA and DOX in human blood serum and urine samples. Graphical Abstract Fabrication of new oxidized multiwalled carbon nanotube/glassy carbon electrode for simultaneous determination of dopamine and doxorubicin. PMID- 26873213 TI - Systematic and comprehensive strategy for metabolite profiling in bioanalysis using software-assisted HPLC-Q-TOF: magnoflorine as an example. AB - Metabolite profiling plays a crucial role in drug discovery and development, and HPLC-Q-TOF has evolved into a powerful and effective high-resolution analytical tool for metabolite detection. However, traditional empirical identification is laborious and incomplete. This paper presents a systematic and comprehensive strategy for elucidating metabolite structures using software-assisted HPLC-Q-TOF that takes full advantage of data acquisition, data processing, and data mining technologies, especially for high-throughput metabolite screening. This strategy has been successfully applied in the study of magnoflorine metabolism based on our previous report of its poor bioavailability and drug-drug interactions. In this report, 23 metabolites of magnoflorine were tentatively identified with detailed fragmentation pathways in rat biological samples (urine, feces, plasma, and various organs) after i.p. or i.g. administration, and for most of these metabolites, the metabolic sites were determined. The phase I biotransformations of magnoflorine (M1-M7, M10-M14) consist of demethylation, dehydrogenation, hydroxylation, methylene to ketone transformation, N-ring opening, and dehydroxylation. The phase II biotransformations (M8, M9, and M15-M23) consist of methylation, acetylation, glucuronidation, and N-acetylcysteine conjugation. The results indicate that the extensive metabolism and wide tissue distribution of magnoflorine and its metabolites may partly contribute to its poor bioavailability and drug-drug interaction, and i.p. administration should thus be a suitable approach for isolating magnoflorine metabolites. In summary, this strategy could provide an efficient, rapid, and reliable method for the structural characterization of drug metabolites and may be applicable for general Q-TOF users. PMID- 26873214 TI - Development of a passive sampler based on a polymer inclusion membrane for total ammonia monitoring in freshwaters. AB - A passive sampler for determining the time-weighted average total ammonia (i.e. molecular ammonia and the ammonium cation) concentration (C TWA) in freshwaters, which incorporated a polymer inclusion membrane (PIM) as a semi-permeable barrier separating the aqueous source solution from the receiving solution (i.e. 0.8 mol L(-1) HCl), was developed for the first time. The PIM was composed of dinonylnaphthalene sulfonic acid (DNNS) as a carrier, poly (vinyl chloride) (PVC) as a base polymer and 1-tetradecanol as a modifier. Its optimal composition was found to be 35 wt% commercial DNNS, 55 wt% PVC and 10 wt% 1-tetradecanol. The effect of environmental variables such as the water matrix, pH and temperature were also studied using synthetic freshwaters. The passive sampler was calibrated under laboratory conditions using synthetic freshwaters and exhibited a linear response within the concentration range 0.59-2.8 mg L(-1) NH4(+) (0.46-2.1 mg N L(-1)) at 20 degrees C. The performance of the sampler was further investigated under field conditions over 7 days. A strong correlation between spot sampling and passive sampling was achieved, thus providing a proof-of-concept for the passive sampler for reliably measuring the C(TWA) of total ammonia in freshwaters, which can be used as an indicator in tracking sources of faecal contamination in stormwater drains. PMID- 26873216 TI - An efficient quantitation strategy for hydroxyl radical-mediated protein footprinting using Proteome Discoverer. AB - Hydroxyl radical protein footprinting coupled with mass spectrometry has become an invaluable technique for protein structural characterization. In this method, hydroxyl radicals react with solvent exposed amino acid side chains producing stable, covalently attached labels. Although this technique yields beneficial information, the extensive list of known oxidation products produced make the identification and quantitation process considerably complex. Currently, the methods available for analysis either involve manual analysis steps, or limit the amount of searchable modifications or the size of sequence database. This creates a bottleneck which can result in a long and arduous analysis process, which is further compounded in a complex sample. Here, we report the use of a new footprinting analysis method for both peptide and residue-level analysis, demonstrated on the GCaMP2 synthetic construct in calcium free and calcium bound states. This method utilizes a customized multi-search node workflow developed for an on-market search platform in conjunction with a quantitation platform developed using a free Excel add-in. Moreover, the method expedites the analysis process, requiring only two post-search hours to complete quantitation, regardless of the size of the experiment or the sample complexity. PMID- 26873215 TI - Screening of lipase inhibitors from Scutellaria baicalensis extract using lipase immobilized on magnetic nanoparticles and study on the inhibitory mechanism. AB - Scutellaria baicalensis is a traditional Chinese medicinal plant possessing a wide variety of biological activities. In this work, lipase immobilized on magnetic nanoparticles (LMNPs) was used as solid phase extract absorbent for screening of lipase inhibitors from this plant. Three flavonoids were found to bind to LMNPs and were identified as baicalin, wogonin, and oroxylin A by liquid chromatography-mass spectrometry (HPLC-MS). Their IC50 values were determined to be 229.22 +/- 12.67, 153.71 +/- 9.21, and 56.07 +/- 4.90 MUM, respectively. Fluorescence spectroscopy and molecular docking were used to probe the interactions between these flavonoids and lipase. All the flavonoids quenched the fluorescence of lipase statically by forming new complexes, implying their affinities with the enzyme. The thermodynamic analysis suggested that van der Waals force and hydrogen bond were the main forces between wogonin and lipase, while hydrophobic force was the main force for the other two flavonoids. The results from a molecular docking study further revealed that all of them could insert into the pocket of lipase binding to a couple of amino acid residues. PMID- 26873217 TI - Rapid quantification method for Legionella pneumophila in surface water. AB - World-wide legionellosis outbreaks caused by evaporative cooling systems have shown that there is a need for rapid screening methods for Legionella pneumophila in water. Antibody-based methods for the quantification of L. pneumophila are rapid, non-laborious, and relatively cheap but not sensitive enough for establishment as a screening method for surface and drinking water. Therefore, preconcentration methods have to be applied in advance to reach the needed sensitivity. In a basic test, monolithic adsorption filtration (MAF) was used as primary preconcentration method that adsorbs L. pneumophila with high efficiency. Ten-liter water samples were concentrated in 10 min and further reduced to 1 mL by centrifugal ultrafiltration (CeUF). The quantification of L. pneumophila strains belonging to the monoclonal subtype Bellingham was performed via flow based chemiluminescence sandwich microarray immunoassays (CL-SMIA) in 36 min. The whole analysis process takes 90 min. A polyclonal antibody (pAb) against L. pneumophila serogroup 1-12 and a monoclonal antibody (mAb) against L. pneumophila SG 1 strain Bellingham were immobilized on a microarray chip. Without preconcentration, the detection limit was 4.0 * 10(3) and 2.8 * 10(3) CFU/mL determined by pAb and mAb 10/6, respectively. For samples processed by MAF-CeUF prior to SMIA detection, the limit of detection (LOD) could be decreased to 8.7 CFU/mL and 0.39 CFU/mL, respectively. A recovery of 99.8 +/- 15.9% was achieved for concentrations between 1-1000 CFU/mL. The established combined analytical method is sensitive for rapid screening of surface and drinking water to allow fast hygiene control of L. pneumophila. PMID- 26873218 TI - Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS. AB - A deficiency of alpha-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though alpha-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids. PMID- 26873219 TI - Copper ion detection using novel silver nanoclusters stabilized with amido black 10B. AB - Novel fluorescent silver nanoclusters (AgNCs) were synthesized using amido black 10B (AB) as a stabilizing agent and then employed for the detection of copper ions (Cu(2+)). The AB-stabilized AgNCs (AB-AgNCs) were well dispersed in aqueous solution with an average diameter of around 1.3 nm and exhibited illustrious blue fluorescence emission. Moreover, the fluorescence of AB-AgNCs could be quenched efficiently by Cu(2+), which might be a result of the coordination between Cu(2+) and the free recognition group of AB on surfaces of AB-AgNCs, inducing the aggregation of AB-AgNCs. Based on the linear decrease of fluorescence intensity, the Cu(2+) concentration was determined in the range of 0.01-1.1 MUmol L(-1) and the limit of detection (LOD) was 4.0 nMU. In addition, the detection of Cu(2+) could be performed with AB-AgNCs in the presence of other ions, including 13 kinds of conventional metal ions and 11 kinds of anions. Based on the above experiment, the developed AB-AgNC probe was successfully further applied to detect Cu(2+) in three electroplating effluents, which showed high accuracy. PMID- 26873221 TI - Chengru Feng: The founder of biological illustration in China. PMID- 26873220 TI - Composition of ultrathin binary polymer brushes by thermogravimetry-gas chromatography-mass spectrometry. AB - In the present paper, a reliable and rugged thermogravimetry-gas chromatography mass spectrometry (TGA-GC-MS) method was developed to determine the composition of ultrathin films consisting of binary blends of functional polystyrene (PS) and polymethylmethacrylate (PMMA) grafted to a silicon wafer. A general methodology will be given to address the composition determination problem for binary or even multicomponent polymer brush systems using the PS/PMMA-based samples as a paradigmatic example. In this respect, several distinct tailor-made materials were developed to ensure reliable calibration and validation stages. The analytical method was tested on unknown samples to follow the composition evolution in PS/PMMA brushes during the grafting reaction. A preferential grafting of the PMMA was revealed in full agreement with its preferential interaction with the SiO2 polar surface. PMID- 26873222 TI - Erratum to: Archetype relational mapping - a practical openEHR persistence solution. PMID- 26873224 TI - Chancellor's psychiatrist brother is struck off medical register. PMID- 26873223 TI - Mitochondrial DNA assessment of Phytophthora infestans isolates from potato and tomato in Ethiopia reveals unexpected diversity. AB - Mitochondrial DNA (mtDNA) haplotypes were determined using restriction fragment length polymorphism (RFLP) for P. infestans sampled from 513 foliar lesions of late blight found on potato and tomato in different regions of Ethiopia. Among the four reported mitochondrial haplotypes of Phytophthora infestans, Ia, Ib and IIb were detected in 93 % of the samples analyzed but the vast majority of these were Ia. The remaining 7 % represented a previously unreported haplotype. DNA sequencing of this new haplotype also confirmed a single base nucleotide substitution that resulted in loss of EcoRI restriction site and gain of two additional MspI sites in cox1 and atp1 genes, respectively. There were 28 polymorphic sites among all nucleotide sequences including five reference isolates. Sites with alignment gaps were observed in P4 with one nucleotide deletion in 11 Ethiopian isolates. None of the reference sequence produced frame shifts, with the exception of the 3-nucleotide deletion in the P4 region by Phytophthora andina, a feature that can be used to distinguish the new Ethiopian isolates from P. andina. While a distinguishing molecular data presented here clearly separated them from P. infestans, 7 % of the isolates that share this feature formed an important component of the late blight pathogen causing disease on Solanum tuberosum in Ethiopia. Thus, these Ethiopian isolates could represent a novel Phytophthora species reported for the first time here. PMID- 26873225 TI - Clinical evaluation of the effect of diquafosol ophthalmic solution in glaucoma patients with dry eye syndrome. AB - PURPOSE: To investigate the effects of diquafosol on intraocular pressure (IOP) and dry eye symptoms in glaucoma patients with dry eye syndrome (DES). METHODS: This study evaluated a total of 138 glaucoma patients with DES who were treated with diquafosol ophthalmic solution (DIQUAS((r))). Before treatment and 1, 4, 12, 36, and 52 weeks after treatment, IOP, ocular surface disease index (OSDI), tear film break-up time (BUT), Schirmer I test scores, fluorescein staining, conjunctival impression cytology, and adverse drug reactions were evaluated. RESULTS: Throughout the treatment period, the mean IOP for all the patients remained stable after treatment with diquafosol (15.4 +/- 2.8 mmHg at baseline and 16.0 +/- 2.8 mmHg at 52 weeks). The mean OSDI score improved significantly at 4, 12, and 52 weeks after diquafosol treatment. The BUT and Schirmer I test scores were significantly increased after diquafosol treatment. The Oxford scheme score was significantly decreased at 1, 4, 12, 36, and 52 weeks after diquafosol treatment. A significant improvement in goblet cell density was observed after 4 weeks of treatment with diquafosol. Adverse drug reactions were reported in 22 (15.9 %) patients. There were no serious adverse drug reactions. CONCLUSIONS: Diquafosol was effective in improving objective and subjective symptoms and maintained a stable IOP in glaucoma patients with DES. Therefore, the addition of diquafosol treatment in glaucoma patients with DES or ocular surface side effects using anti-glaucoma medication may be beneficial. PMID- 26873226 TI - Reprint of: Locus coeruleus neuronal activity determines proclivity to consume alcohol in a selectively-bred line of rats that readily consumes alcohol. AB - Sprague-Dawley rats selectively-bred for susceptibility to stress in our laboratory (Susceptible, or SUS rats) voluntarily consume large amounts of alcohol, and amounts that have, as shown here, pharmacological effects, which normal rats will not do. In this paper, we explore neural events in the brain that underlie this propensity to readily consume alcohol. Activity of locus coeruleus neurons (LC), the major noradrenergic cell body concentration in the brain, influences firing of ventral tegmentum dopaminergic cell bodies of the mesocorticolimbic system (VTA-DA neurons), which mediate rewarding aspects of alcohol. We tested the hypothesis that in SUS rats alcohol potently suppresses LC activity to markedly diminish LC-mediated inhibition of VTA-DA neurons, which permits alcohol to greatly increase VTA-DA activity and rewarding aspects of alcohol. Electrophysiological single-unit recording of LC and VTA-DA activity showed that in SUS rats alcohol decreased LC burst firing much more than in normal rats and as a result markedly increased VTA-DA activity in SUS rats while having no such effect in normal rats. Consistent with this, in a behavioral test for reward using conditioned place preference (CPP), SUS rats showed alcohol, given by intraperitoneal (i.p.) injection, to be rewarding. Next, manipulation of LC activity by microinfusion of drugs into the LC region of SUS rats showed that (a) decreasing LC activity increased alcohol intake and increasing LC activity decreased alcohol intake in accord with the formulation described above, and (b) increasing LC activity blocked both the rewarding effect of alcohol in the CPP test and the usual alcohol-induced increase in VTA-DA single-unit activity seen in SUS rats. An important ancillary finding in the CPP test was that an increase in LC activity was rewarding by itself, while a decrease in LC activity was aversive; consequently, effects of LC manipulations on alcohol-related reward in the CPP test were perhaps even larger than evident in the test. Finally, when increased LC activity was associated with (i.e., conditioned to) i.p. alcohol, subsequent alcohol consumption by SUS rats was markedly reduced, indicating that SUS rats consume large amounts of alcohol because of rewarding physiological consequences requiring increased VTA-DA activity. The findings reported here are consistent with the view that the influence of alcohol on LC activity leading to changes in VTA-DA activity strongly affects alcohol-mediated reward, and may well be the basis of the proclivity of SUS rats to avidly consume alcohol. PMID- 26873227 TI - Follow-up duration influences the relative importance of OGTT and optimal timing of glucose measurements for predicting future type 2 diabetes. AB - OBJECTIVE: To examine the impact of follow-up duration on the incremental prognostic yield of a baseline oral glucose tolerance test (OGTT) for predicting type 2 diabetes and to assess the discrimination ability of blood glucose (BG) obtained at different time points during OGTT. DESIGN: A prospective, population based cohort study (Malmo Preventive Project) with inclusion of subjects from 1974 to 1992. METHODS: A total of 5256 men without diabetes, who had BG measured at 0, 20, 40, 60, 90, and 120 min during OGTT (30 g/m2 glucose), were followed for 30 years. Incident type 2 diabetes was recorded using registries. The performance of OGTT added to a clinical prediction model (age, body mass index (BMI), diastolic blood pressure, fasting BG, triglycerides, and family history of diabetes) was assessed using Harrell's concordance index (C-index) and integrated discrimination improvement (IDI). RESULTS: Median age was 48 years, mean BMI 24.9 kg/m2, and mean fasting BG 4.7 mmol/L. Models with added post-load BG performed better than the clinical model (C-index: P = 0.08 for BG at 120 min at 5 years, otherwise P <= 0.045; IDI: P >= 0.06 for BG at 60 and 90 min at 5 years, otherwise P <= 0.01). With a longer follow-up duration, C-index decreased, and the C-index increase associated with OGTT was attenuated. Models including BG at 60 or 90 min performed significantly better than the model with BG at 120 min, evident beyond follow-up of 10 and 5 years, respectively. CONCLUSIONS: OGTT provided incremental prognostic yield for type 2 diabetes prediction. BG measured at 60 or 90 min provided better discrimination than BG at 120 min. PMID- 26873228 TI - A Single-Dose Crossover Pharmacokinetic Comparison Study of Oral, Rectal and Topical Quetiapine in Healthy Adults. AB - INTRODUCTION: Quetiapine is an oral atypical antipsychotic drug commonly used to treat a large number of neuropsychiatric disorders and conditions. However, a substantial number of patients who may benefit from treatment with quetiapine are unable to ingest quetiapine or other medications by mouth and thus require alternative routes of administration. There are currently no studies evaluating non-oral compounded dosage forms of quetiapine. METHODS: We conducted a single dose open-label crossover pharmacokinetic study in 10 healthy adults to determine whether quetiapine compounded as a rectal suppository or a topical cream achieved absorption similar to that achieved by a commercially available oral formulation. RESULTS: Rectal quetiapine produced an area under the plasma concentration-time curve from time zero to infinity (AUCinfinity) approximately 90 % greater than that produced by an equal (milligram per milligram) dose of oral quetiapine (15,333 ng/mL versus 8118.8 ng/mL, p = 0.005). However, only two of ten subjects who received topical quetiapine had detectable serum levels. When detected, serum levels achieved with topical quetiapine were delayed and low in comparison with those produced by the oral and rectal dosage forms. CONCLUSION: Our results suggest that rectal, but not topical, quetiapine may be useful in clinical settings. Clinical outcome studies of rectal quetiapine are needed. PMID- 26873230 TI - [Clinical Importance of Central Nervous System Dysfunction in Myopathy]. AB - Multidisciplinary treatments including mechanical ventilation and cardioprotective therapy have improved life expectancy in many neuromuscular disorders such as Duchenne muscular dystrophy. For these patients, central nervous system disturbances such as intellectual and/or developmental disability can hinder social activities and communications. In myotonic dystrophy, the personality and/or cognitive dysfunction affects medical consultation behavior and decreases the efficacy of medical treatments. Understanding central nervous system disturbances in myopathies and providing care keeping in mind the patient burden are critical for improving prognosis and quality of life. PMID- 26873229 TI - Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers and Subjects with Multiple Sclerosis: Analysis of Phase I-III Clinical Trials. AB - BACKGROUND AND OBJECTIVES: Daclizumab high-yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the alpha-subunit (CD25) of the interleukin-2 receptor. The present work characterized the population pharmacokinetics of daclizumab HYP in healthy volunteers (HVs) and subjects with relapsing-remitting multiple sclerosis (RRMS) and evaluated the effects of covariates on daclizumab HYP exposure. METHODS: Measurable serum concentrations (n = 17,139) from 1670 subjects in seven clinical studies (three phase I, one immunogenicity, one phase II with extension, and one phase III) were included in this pharmacokinetic analysis using non-linear mixed-effects modeling. The three phase I studies evaluated single or multiple doses that ranged from 50 to 400 mg with either intravenous or subcutaneous (SC) administration in HVs (n = 71). The phase II with extension studies evaluated doses of 150 or 300 mg SC every 4 weeks (n = 567), and the immunogenicity (n = 113) and the phase III (n = 919) studies evaluated 150 mg SC every 4 weeks, all in RRMS patients. RESULTS: A two compartment model with first-order absorption and elimination adequately described daclizumab HYP pharmacokinetics. Clearance (CL) was 0.212 L/day and the central volume of distribution was 3.92 L, scaled by [body weight (kg)/68] with exponents of 0.87 and 1.12, respectively. The peripheral volume of distribution was 2.42 L. Absorption lag time, mean absorption time, and absolute bioavailability (100-300 mg SC) were 1.61 h, 7.2 days, and 88 %, respectively. The daclizumab HYP terminal half-life was 21 days. Baseline CD25, age, and sex did not influence daclizumab HYP pharmacokinetics. Body weight explained 37 and 27 % of the inter-individual variability for CL and central volume of distribution, respectively. Neutralizing antibody (NAb)-positive status (included as a time-varying covariate) increased daclizumab HYP CL by 19 %. CONCLUSIONS: Consistent with previous findings in HVs, this analysis including extensive data from RRMS patients demonstrates that daclizumab HYP is characterized by slow CL, linear pharmacokinetics at doses above 100 mg, and high SC bioavailability. The pharmacokinetics of daclizumab HYP were not influenced by age (range 18-66 years), the sex of adult subjects, or the baseline CD4+CD25+ T cells (target level). The impact of covariates (body weight, NAb) on daclizumab HYP pharmacokinetics is unlikely to be clinically relevant. PMID- 26873231 TI - [Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy]. AB - Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via alpha-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications. PMID- 26873232 TI - [Dystrophinopathy and Seizure]. AB - Dystrophinopathy is associated strongly with central nervous system manifestation. It has been reported that 4%-15% of patients with dystrophinopathy have febrile seizure, and 2%-12% have epilepsy. In our study, 8% of patients had febrile seizure, and it was more common in patients with mutations downstream of exon 45, especially exon 63. Epilepsy occurred in 5% of our patients, and the prevalence in Becker muscular dystrophy was higher than that in Duchenne muscular dystrophy. Isoforms such as Dp427 and Dp71, expressed in the central nervous system. might be related to seizure, because of impairment in GABAA receptors, aquaporin 4, and K channels. PMID- 26873233 TI - [Social Cognitive Impairment in Myotonic Dystrophy Type 1]. AB - Myotonic dystrophy type 1 (DM 1) is a heritable, multisystem disease that affects not only the muscles but also the brain. DM 1 is often accompanied by developmental behavioral disorders, such as autism spectrum disorders. The autistic traits in DM 1 may be related to social cognitive dysfunction. The social cognitive function of patients with DM 1 was examined with respect to facial emotion recognition and theory of mind, which is the specific cognitive ability to understand the mental states of other people. With respect to facial emotion recognition, the sensitivities to disgust and anger were lower among patients with DM 1 than among healthy subjects, and this difference could not be attributed to visual impairment. To examine the theory of mind ability, the "Reading the Mind in the Eyes" test and the faux pas recognition test were used. Patients with DM 1 were found to be impaired in both tests, but the results were not attributed to visual ability and lexical comprehension. The possible causes of social cognitive dysfunction in DM 1 are the l cerebral atrophy and white matter abnormalities in the temporal, frontal, and insular cortex. Dysfunctions in these areas may affect the emotional and theory of mind abilities in DM 1, which result in the behavioral and communication disorders. PMID- 26873234 TI - [Impairment of Odor Recognition in Myotonic Dystrophy Type 1]. AB - There is evidence that impaired human cognitive abilities are reflected in loss of olfactory abilities. Declining olfactory perception may be a biomarker for impairment of cognitive function and of impending illnesses in neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Previously, we reported that patients with myotonic dystrophy type 1 (DM 1) had lower sensitivity to emotional facial expressions as well as abnormal olfactory threshold or recognition level. In DM 1, pathological studies have reported neurofibrillary tangles in several temporal areas including the entorhinal cortex (ENT), hippocampus (HI), and the amygdala. We observed that patients with DM 1 showed signal abnormalities in the olfactory limbic areas on magnetic resonance imaging. Our findings underscore the need to pay careful attention to significant decreases in odor identification abilities caused by diverse forms of abnormal brain function, especially in the AMG, ENT and HI. PMID- 26873235 TI - [Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)]. AB - Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84 99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels. PMID- 26873236 TI - [Genes Responsible for Epileptic Syndromes]. AB - The first causative gene for epileptic syndrome was revealed 20 years ago. Since then, many genes responsible for epileptic syndrome, particularly sporadic epileptic encephalopathies, such as Ohtahara syndrome, West syndrome, and focal cortical dysplasia, have been identified. Although epilepsy was recognized as a channelopathy in the beginning stages of gene discovery, other molecular mechanisms for epileptic syndromes, such as interneuronopathy, synaptic vesicle release, and mTOR signal transduction, are emerging. A new technique for gene analysis using the next-generation sequencer is now available for clinical purpose abroad and precision medicine based on the molecular mechanisms has started. Infrastructural development of the official framework, from molecular diagnosis to personalized therapy, is urgently required in Japan. PMID- 26873237 TI - [Clinical Neuropsychology of Dementia with Lewy Bodies]. AB - Dementia with Lewy bodies (DLB) shows lesser memory impairment and more severe visuospatial disability than Alzheimer disease (AD). Although deficits in both consolidation and retrieval underlie the memory impairment, retrieval deficit is predominant in DLB. Visuospatial dysfunctions in DLB are related to the impairments in both ventral and dorsal streams of higher visual information processing, and lower visual processing in V1/V2 may also be impaired. Attention and executive functions are more widely disturbed in DLB than in AD. Imitation of finger gestures is impaired more frequently in DLB than in other mild dementia, and provides additional information for diagnosis of mild dementia, especially for DLB. Pareidolia, which lies between hallucination and visual misperception, is found frequently in DLB, but its mechanism is still under investigation. PMID- 26873238 TI - [Early Detection of Manganese Intoxication Based on Occupational History and T1 weighted MRI]. AB - Manganese regulates many enzymes and is essential for normal cell function. Chronic manganese intoxication has an insidious and progressive course terminating to atypical parkinsonism with little therapeutic efficacy. For subjects with chronic manganese exposure such as welders, manganese intoxication can be detected early based on the presence of hyperintensity in the globus pallidus on T(1)-weighted MRI and abnormally high urinary excretion of manganese with a chelating agent even in cases of normal serum/urine level of manganese. PMID- 26873239 TI - [Argatroban, Aspirin, and Clopidogrel Combination Therapy for Acute Penetrating Artery Infarction: A Pilot Study]. AB - Treatment to prevent progressive neurological deficits in acute penetrating artery infarction (API) is clinically important, but has not yet been established. This study aims to investigate the efficacy and safety of argatroban, aspirin, and clopidogrel combination therapy for API. Patients with API (lacunar infarcts or branch atheromatous disease) admitted within 48 hours after onset were enrolled. We assigned them to argatroban, aspirin, and clopidogrel (AAC) group or argatroban and aspirin (AA) group. In both groups, blood pressure was controlled to near or below 180/105 mmHg in the admission period. We defined progressing stroke as a worsening of two or more points in the National Institutes of Health Stroke Scale score on the seventh day of admission. Fifty-four patients were enrolled. We assigned 28 patients to the AAC group, and 26 patients to the AA group. There were no significant differences in background factors between the two groups. The incidence of progressing stroke was significantly higher in the AA group (P<0.05). Intracranial hemorrhage or any other bleeding was not seen in the admission period in either group. Our findings suggest that the AAC combination therapy may positively affect progressive neurological deficits in API patients. PMID- 26873240 TI - [A Patient with Cervical Spondylotic Myelopathy with 18F-FDG Uptake on Positron Emission Tomography/Computed Tomography]. PMID- 26873241 TI - Early beta-cell dysfunction characterizes males with type 2 diabetes of Yemenite origin. AB - AIMS: The aim of the current study was to characterize beta-cell function, insulin sensitivity and line of inheritance in patients with recent-onset type 2 diabetes of Yemenite and non-Yemenite Jewish origin. METHODS: A cohort study including 121 GAD negative diabetic patients, 59 of Yemenite and 62 of non Yemenite origin, treated by diet +/- oral antihyperglycemic monotherapy who underwent 180-min meal tolerance test (MMT). Based on MMT, indexes of insulin resistance and secretion were calculated. RESULTS: There were no significant differences in age, sex, diabetes duration, BMI, HbA1c and lipid profile. A significant difference was found in family history of diabetes: 63 % of patients of Yemenite origin had maternal inheritance versus 35 % in the non-Yemenite origin (p < 0.001). Both indexes of beta-cell function, the insulinogenic and the disposition indexes were significantly lower in patients of Yemenite origin compared with non-Yemenite origin (0.66 +/- 0.4 vs. 0.93 +/- 0.8, p = 0.04; 2.3 +/- 1.8 vs. 3.3 +/- 3.3, p = 0.04, respectively) with no difference in insulin sensitivity. When females and males were analyzed separately, the difference in maternal inheritance remained significant in both, but the difference in beta cell function indexes was observed only in males (p = 0.03, p = 0.01, respectively). CONCLUSIONS: Males with recent-onset diabetes of Yemenite origin have a significant reduction of beta-cell function and reduced ability to compensate for insulin resistance compared with diabetic males of non-Yemenite origin. Both males and females of Yemenite origin have a significantly higher maternal inheritance of diabetes. These data suggest different underlying mechanisms leading to early loss of beta-cell in diabetic males of Yemenite origin. PMID- 26873242 TI - The effect of a single dose of vitamin D on glycemic status and C-reactive protein levels in type 2 diabetic patients with ischemic heart disease: a randomized clinical trial. AB - AIMS: To assess whether a single parental dose of 25-hydroxy vitamin D [25(OH)Vit D] could improve glucose control and inflammation in type 2 diabetic patients (T2D) with ischemic heart disease (IHD). METHODS: A randomized, placebo controlled, double-blind trial was performed on 95 patients (47-placebo and 48 vitamin D groups). Participants were randomized using a randomization table to a single dose of either vitamin D (300,000 IU, IM) or a matching placebo. Fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), 25(OH)Vit D and high sensitivity C-reactive protein (hs-CRP) were measured at baseline and at 8 weeks. RESULTS: No significant differences in baseline values were noted between groups, except in HbA1c, which was lower in the placebo group. In the supplemented group, the level of serum 25(OH)Vit D increased (29.6 +/- 20.8 vs. 44.5 +/- 19.2 ng/mL) and those of FBS and HbA1c decreased significantly [186.5 +/- 64.1 vs. 165.1 +/- 58.5 mg/dL and 8.2 +/- 2.0 % (66.3 +/- 21.8 mmol/mol) vs. 7.7 +/- 1.8 % (61.7 +/- 20.0 mmol/mol), respectively] (all p < 0.05), and no changes, however, were observed in the placebo group. We also compared change of marginal means of outcome variables (HbA1c, FBS, 25(OH)Vit D and hs-CRP) from baseline between the vitamin D versus placebo group, using ANCOVA, adjusted for the baseline of each variable itself, season at study entry, age and body mass index. During trial, only HbA1c level decreased significantly [0.48 % (standard error: 0.17), p = 0.04]. No any adverse effect was seen. CONCLUSIONS: A single parenteral dose of vitamin D in T2D patients with IHD improved glycemic control, but not inflammatory status. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trial Registry. CLINICAL TRIAL NUMBER: ACTRN12614000529640. PMID- 26873243 TI - Systemic antibiotic therapy does not significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus. AB - INTRODUCTION: Treatment of implant-associated osteomyelitis regularly involves the use of systemic antibiotics in addition to surgical intervention. However, it remains unclear if perioperative systemic application of bactericide substances can improve overall outcome in models of severe intramedullary infection. The present study investigated the use of systemic gentamicin in addition to a controlled local release from a highly lipophilic gentamicinpalmitate compound while the previous study showed efficacy of sole antibiotic implant-coating. METHODS: Forty male Sprague-Dawley rats were divided into two groups receiving an intramedullary femoral injection of 10(2) CFU of a common methicillin susceptible Staphylococcus aureus strain (MSSA Rosenbach). Group I received an uncoated implant whereas group II received a coated implant. All animals received a single shot intraperitoneal application of gentamicinsulfate directly after wound closure while the historical control group III (n = 20) had no antibiotic treatment at all. Animals were observed for 28 and 42 days. Serum haptoglobin and relative weight gain were assessed as well as roll over cultures of explanted femur nails and histological scores of periprosthetic infection in dissected femora. RESULTS: Systemic application of gentamicin combined with antibiotic coated implant did not further reduce bacterial growth significantly compared with systemic or local antibiotic application alone. Combined local and systemic therapy reduced serum haptoglobin significantly after day 7, 28 and 42 whereas systemic application alone did not compare to controls. CONCLUSIONS: Systemic perioperative and implant-associated application of antibiotics were both comparably effective to treat implant-associated infections whereas the combined antibiotic therapy further reduced systemic signs of infection time dependent. PMID- 26873244 TI - Proteomics of terpenoid biosynthesis and secretion in trichomes of higher plant species. AB - Among the specialized (secondary) plant metabolites, terpenoids represent the most diverse family and are often involved in the defense against pathogens and herbivores. Terpenoids can be produced both constitutively and in response to the environment. At the front line of this defense strategy are the glandular trichomes, which are organs dedicated primarily to the production of specialized metabolites. Mass spectrometry-based proteomics is a powerful tool, which is very useful to investigate enzymes involved in metabolic pathways, such as the synthesis and secretion of terpenoids in glandular trichomes. Here we review the strategies used to investigate the specific roles of these particular organs from non-model plant species, mainly belonging to the Lamiaceae, Solanaceae, and Cannabaceae families. We discuss how proteomics helps to accurately pinpoint candidate proteins to be functionally characterized, and how technological progresses create opportunities for studying low-abundance proteins, such as the ones related to the synthesis and transport of specialized metabolites. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID- 26873246 TI - Novel RIPK3 inhibitors discovered through a structure-based approach exert post ischemic neuroprotection. AB - Necroptosis or programmed necrosis is evident in various neurological disorders such as ischemic stroke. Receptor interacting serine/threonine protein kinase 3 (RIPK3) is one of the crucial targets of necroptosis and inhibition of this protein exerts neuroprotection. However, knowledge regarding the three dimensional structure and binding site information of this protein is lacking. In the present study, structure-based in silico methods were implemented to identify the key amino acids in the RIPK3 binding site that might be responsible for ligand interactions. Further, novel RIPK3 inhibitors were identified through a dual ensemble screening strategy. Three inhibitors exhibited binding to RIPK3 in micromolar concentrations and exerted post-ischemic neuroprotection in vitro. PMID- 26873247 TI - Rabbit syndrome associated with medullary compression by vertebral artery. PMID- 26873245 TI - Localization of the binding interface between leiomodin-2 and alpha-tropomyosin. AB - The development of some familial dilated cardiomyopathies (DCM) correlates with the presence of mutations in proteins that regulate the organization and function of thin filaments in cardiac muscle cells. Harmful effects of some mutations might be caused by disruption of yet uncharacterized protein-protein interactions. We used nuclear magnetic resonance spectroscopy to localize the region of striated muscle alpha-tropomyosin (Tpm1.1) that interacts with leiomodin-2 (Lmod2), a member of tropomodulin (Tmod) family of actin-binding proteins. We found that 21 N-terminal residues of Tpm1.1 are involved in interactions with residues 7-41 of Lmod2. The K15N mutation in Tpm1.1, known to be associated with familial DCM, is located within the newly identified Lmod2 binding site of Tpm1.1. We studied the effect of this mutation on binding Lmod2 and Tmod1. The mutation reduced binding affinity for both Lmod2 and Tmod1, which are responsible for correct lengths of thin filaments. The effect of the K15N mutation on Tpm1.1 binding to Lmod2 and Tmod1 provides a molecular rationale for the development of familial DCM. PMID- 26873248 TI - Non-essential contribution of LRRC8A to volume regulation. AB - Volume regulation is an essential property of any living cell and needs to be tightly controlled. While different types of K(+) channels have been found to participate in the regulation of cell volume, the newly identified volume regulated anion channel (VRAC) LRRC8 has been claimed to be essential for volume regulation. In unbiased genome-wide small interfering RNA (siRNA) screens, two independent studies identified LRRC8A/Swell1 as an essential component of VRAC, thus being indispensable for cellular volume regulation. We reanalyzed the role of LRRC8A for VRAC and regulatory volume decrease (RVD) in several cell types and under various conditions. While the role of LRRC8A for VRAC and its contribution to RVD is confirmed, we find that it is not essential for swelling-activated anion currents or cellular volume regulation, or apoptotic cell shrinkage. The contribution of LRRC8A is variable and largely depending on the cell type. PMID- 26873249 TI - Explore the variation of MMP3, JNK, p38 MAPKs, and autophagy at the early stage of osteoarthritis. AB - Osteoarthritis is a chronic disease characterized by cartilage degeneration and chondrocyte apoptosis. Mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in regulating OA process. Autophagy has an important effect on the OA process, and it is believed to be regulated by MAPKs. To reveal the mechanism and the effect of JNK and p38 MAPKs on matrix metalloproteinase 3 (MMP3) and autophagy in OA, the study established OA model in rabbits, used the measurement of the Osteoarthritis Research Society International scoring system to evaluate OA model, and conducted general observation, histological observation, and Western blotting of JNK, phosphorylate-JNK (P-JNK), p38, phosphorylate-p38 (P-p38), MMP3, and light-chain 3 (LC3)-II/LC3-I to explore the variation of JNK, p38 MAPKs, and autophagy at the early stage of OA. With OA progressing at the early stage, MMP3, P-p38, and P-JNK were gradually upregulated from the baseline to the peak in study groups when compared with the control group; JNK and p38 variated of turbulence without statistical difference; and LC3 II/LC3-I had a decreasing tendency from the 0- to 15-day group. This study identifies that compromised autophagy may be related to the OA progress and that JNK and p38 MAPKs have positive regulation on MMP3 and negative regulation on autophagy. It also implicates a new therapeutic strategy for OA and other degenerate diseases based on selective MAPK inhibitors, reduction of MMP3, and autophagy. PMID- 26873252 TI - [Neurological diseases after lightning strike : Lightning strikes twice]. AB - Lightning strikes rarely occur but 85 % of patients have lightning-related neurological complications. This report provides an overview about different modes of energy transfer and neurological conditions related to lightning strikes. Moreover, two case reports demonstrate the importance of interdisciplinary treatment and the spectrum of neurological complications after lightning strikes. PMID- 26873253 TI - Dual-process cognitive interventions to enhance diagnostic reasoning: a systematic review. AB - BACKGROUND: Diagnostic error incurs enormous human and economic costs. The dual process model reasoning provides a framework for understanding the diagnostic process and attributes certain errors to faulty cognitive shortcuts (heuristics). The literature contains many suggestions to counteract these and to enhance analytical and non-analytical modes of reasoning. AIMS: To identify, describe and appraise studies that have empirically investigated interventions to enhance analytical and non-analytical reasoning among medical trainees and doctors, and to assess their effectiveness. METHODS: Systematic searches of five databases were carried out (Medline, PsycInfo, Embase, Education Resource Information Centre (ERIC) and Cochrane Database of Controlled Trials), supplemented with searches of bibliographies and relevant journals. Included studies evaluated an intervention to enhance analytical and/or non-analytical reasoning among medical trainees or doctors. FINDINGS: Twenty-eight studies were included under five categories: educational interventions, checklists, cognitive forcing strategies, guided reflection, instructions at test and other interventions. While many of the studies found some effect of interventions, guided reflection interventions emerged as the most consistently successful across five studies, and cognitive forcing strategies improved accuracy and confidence judgements. Significant heterogeneity of measurement approaches was observed, and existing studies are largely limited to early-career doctors. CONCLUSIONS: Results to date are promising and this relatively young field is now close to a point where these kinds of cognitive interventions can be recommended to educators. Further research with refined methodology and more diverse samples is required before firm recommendations may be made for medical education and policy; however, these results suggest that such interventions hold promise, with much current enthusiasm for new research. PMID- 26873250 TI - Bacterial Interactomes: Interacting Protein Partners Share Similar Function and Are Validated in Independent Assays More Frequently Than Previously Reported. AB - Numerous affinity purification-mass spectrometry (AP-MS) and yeast two-hybrid screens have each defined thousands of pairwise protein-protein interactions (PPIs), most of which are between functionally unrelated proteins. The accuracy of these networks, however, is under debate. Here, we present an AP-MS survey of the bacterium Desulfovibrio vulgaris together with a critical reanalysis of nine published bacterial yeast two-hybrid and AP-MS screens. We have identified 459 high confidence PPIs from D. vulgaris and 391 from Escherichia coli Compared with the nine published interactomes, our two networks are smaller, are much less highly connected, and have significantly lower false discovery rates. In addition, our interactomes are much more enriched in protein pairs that are encoded in the same operon, have similar functions, and are reproducibly detected in other physical interaction assays than the pairs reported in prior studies. Our work establishes more stringent benchmarks for the properties of protein interactomes and suggests that bona fide PPIs much more frequently involve protein partners that are annotated with similar functions or that can be validated in independent assays than earlier studies suggested. PMID- 26873251 TI - A Biologist's Field Guide to Multiplexed Quantitative Proteomics. AB - High-throughput genomic and proteomic studies have generated near-comprehensive catalogs of biological constituents within many model systems. Nevertheless, static catalogs are often insufficient to fully describe the dynamic processes that drive biology. Quantitative proteomic techniques address this need by providing insight into closely related biological states such as the stages of a therapeutic response or cellular differentiation. The maturation of quantitative proteomics in recent years has brought about a variety of technologies, each with their own strengths and weaknesses. It can be difficult for those unfamiliar with this evolving landscape to match the experiment at hand with the best tool for the job. Here, we outline quantitative methods for proteomic mass spectrometry and discuss their benefits and weaknesses from the perspective of the biologist aiming to generate meaningful data and address mechanistic questions. PMID- 26873254 TI - Maintaining the link between methodology and method in ethnographic health research. PMID- 26873255 TI - Noncompaction of the Ventricular Myocardium and Polycystic Kidney Disease: A Case Report. AB - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary disorders, characterized by the formation of multiple cysts in the kidneys and other organs, as well as noncystic manifestations such as cerebral aneurysm. The most common cardiovascular disorders associated with ADPKD include valvular abnormalities and aortic aneurysm. An association between ADPKD and impaired left ventricular function has occasionally been reported. We describe a 74-year-old woman with ADPKD and exertional dyspnea. Impaired left ventricular function resulting from noncompaction of the ventricular myocardium (NVM) and secondary left ventricular aneurysm were diagnosed. Cardiac sarcoidosis and ischemic heart disease were ruled out. Myocardial ischemia resulting from NVM was the presumptive cause of the ventricular aneurysm. To our knowledge, this is the first report of concurrent isolated NVM and left ventricular aneurysm in a patient with ADPKD. ADPKD and various cardiomyopathies, including NVM, are all reported to involve mutations of sarcomere genes, suggesting a possible link between the conditions. PMID- 26873257 TI - Greater occipital nerve blockade for the treatment of chronic migraine. PMID- 26873256 TI - Obesity, unhealthy dietary habits and sedentary behaviors among university students in Sudan: growing risks for chronic diseases in a poor country. AB - OBJECTIVE: This study aimed to highlight nutritional status, dietary habits and sedentary patterns among university students in Khartoum state, Sudan. METHODS: A cross-sectional survey was carried out among 400 university students (183 males and 217 females) from University of Khartoum, Sudan. A pre-validated self reported questionnaire was used to collect the data. Weight and height were measured and body mass index was used to determine obesity status. RESULTS: Of the students, 20.5, 14.7, and 1.7 % were underweight, overweight and obese, respectively. The majority of students (85.5 %) consumed breakfast daily. About 45 and 21.8 % of students consumed vegetables and fruit, respectively, on more than 3 days a week. Fast food was consumed significantly more (p < 0.01) for more than 3 days per week by females (44.2 %) than males (27.3 %). Females (42.9 %) were more likely to watch television for 3 h and more per day than males (30.6 %) (p < 0.039). Males (33.9 %) were more prone to sleep for fewer than 7 h per day than females (23 %) (p < 0.016). CONCLUSION: The health authority in Sudan should not only focus on prevention of malnutrition among children but also should organize programs to promote healthy eating and lifestyle among children and youths to prevent and control alarming risk factors for chronic diseases. PMID- 26873258 TI - Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome after bilateral carotid paraganglioma resection: A case report. AB - Background Paraganglioma is a rare neuroendocrine tumour arising anywhere along the paravertebral sympathetic and parasympathetic chains. In the neck, paraganglioma may affect the carotid body (carotid body tumour). Case report We describe a 43-year-old woman who presented with a reversible vasoconstriction syndrome associated with a posterior reversible encephalopathy syndrome following a surgery for a left carotid paraganglioma (with a past medical history of surgery for a right carotid paraganglioma a few months before). Conclusion A consequence of a baroreflex modification is discussed in order to explain the rare occurrence of such symptoms. PMID- 26873261 TI - Nanometer Scale Hard/Soft Bilayer Magnetic Antidots. AB - The effect of arrays of nanometer scale pores on the magnetic properties of thin films has been analyzed. Particularly, we investigated the influence of the out of-plane magnetization component created by the nanopores on the in-plane magnetic behavior of patterned hard/soft magnetic thin films in antidot morphology. Its influence on the coupling in Co/Py bilayers of few tens of nanometer thick is compared for disordered and ordered antidots of 35-nm diameter. The combination of magneto-optical Kerr effect (MOKE) and first-order reversal curve (FORC) technique allows probing the effects of the induced perpendicular magnetization component on the bilayer magnetic behavior, while magnetic force microscopy (MFM) is used to image it. We found that ordered antidots yield a stronger out-of-plane component than disordered ones, influencing in a similar manner the hard layer global in-plane magnetic behavior if with a thin or without soft layer. However, its influence changes with a thicker soft layer, which may be an indication of a weaker coupling. PMID- 26873260 TI - Reexamining the Phosphorus-Protein Dilemma: Does Phosphorus Restriction Compromise Protein Status? AB - Dietary phosphorus restriction is recommended to help control hyperphosphatemia in hemodialysis patients, but many high-phosphorus foods are important sources of protein. In this review, we examine whether restricting dietary phosphorus compromises protein status in hemodialysis patients. Although dietary phosphorus and protein are highly correlated, phosphorus intakes can range up to 600 mg/day for a given energy and protein intake level. Furthermore, the collinearity of phosphorus and protein may be biased because the phosphorus burden of food depends on: (1) the presence of phosphate additives, (2) food preparation method, and (3) bioavailability of phosphorus, which are often unaccounted for in nutrition assessments. Ultimately, we argue that clinically relevant reductions in phosphorus intake can be made without limiting protein intake by avoiding phosphate additives in processed foods, using wet cooking methods such as boiling, and if needed, substituting high-phosphorus foods for nutritionally equivalent foods that are lower in bioavailable phosphorus. PMID- 26873259 TI - Improved visualisation of real-time recordings during third generation cryoballoon ablation: a comparison between the novel short-tip and the second generation device. AB - BACKGROUND: The third-generation Cryoballoon Advance Short-tip (CB-ST) has been designed with a 40 % shortened tip length compared with the former second generation CB advance device (CB-A). Ideally, a shorter tip should permit an improved visualisation of real-time recordings in the pulmonary vein (PV) due to a more proximal positioning of the inner lumen mapping catheter. We sought to compare the incidence of visualisation of real-time recordings in patients having undergone ablation with the CB-ST with patients having received CB-A ablation. METHODS: All patients having undergone CB ablation using CB-ST technology and the last 500 consecutive patients having undergone CB-A ablation were analysed. Exclusion criteria were the presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, and contraindications to general anaesthesia. RESULTS: A total of 600 consecutive patients (58.1 +/- 12.9 years, 64 % males) were evaluated (100 CB-ST and 500 CB-A ablations). Real-time recordings were significantly more prevalent in the CB-ST population compared with CB-A group (85.7 vs 67.2 %, p < 0.0001). Real-time recordings could be more frequently visualised in the CB-ST group in all types of veins (LSPV 89 vs 73.4 %, p = 0.0005; LIPV 84 vs 65.6 %, p = 0.0002; RSPV 87 vs 67.4 %, p < 0.0001; RIPV 83 vs 62.4 %, p < 0.0001). CONCLUSION: The rate of visualisation of real-time recordings is significantly higher during third-generation CB-ST ablation if compared to the second-generation CB-A device. Real-time recordings can be visualised in approximately 85.7 % of veins with this novel cryoballoon. PMID- 26873262 TI - Polycarbonate-Based Blends for Optical Non-linear Applications. AB - This paper presents some investigations on the optical and morphological properties of the polymer (matrix):monomer (inclusion) composite materials obtained from blends of bisphenol A polycarbonate and amidic monomers. For the preparation of the composite films, we have selected monomers characterised by a maleamic acid structure and synthesised them starting from maleic anhydride and aniline derivatives with -COOH, -NO2, -N(C2H5)2 functional groups attached to the benzene ring. The composite films have been deposited by spin coating using a mixture of two solutions, one containing the matrix and the other the inclusion, both components of the composite system being dissolved in the same solvent. The optical transmission and photoluminescence properties of the composite films have been investigated in correlation with the morphology of the films. The scanning electron microscopy and atomic force microscopy have revealed a non-uniform morphology characterised by the development of two distinct phases. We have also investigated the generation of some optical non-linear (ONL) phenomena in these composite systems. The composite films containing as inclusions monomers characterised by the presence of one -COOH or two -NO2 substituent groups to the aromatic nucleus have shown the most intense second-harmonic generation (SHG). The second-order optical non-linear coefficients have been evaluated for these films, and the effect of the laser power on the ONL behaviour of these materials has also been emphasised. PMID- 26873263 TI - On the specific heat capacity enhancement in nanofluids. AB - Molten salts are used as heat transfer fluids and for short-term heat energy storage in solar power plants. Experiments show that the specific heat capacity of the base salt may be significantly enhanced by adding small amounts of certain nanoparticles. This effect, which is technically interesting and economically important, is not yet understood. This paper presents a critical discussion of the existing attendant experimental literature and the phenomenological models put forward thus far. A common assumption, the existence of nanolayers surrounding the nanoparticles, which are thought to be the source of, in some cases, the large increase of a nanofluid's specific heat capacity is criticized and a different model is proposed. The model assumes that the influence of the nanoparticles in the surrounding liquid is of long range. The attendant long range interfacial layers may interact with each other upon increase of nanoparticle concentration. This can explain the specific heat maximum observed by different groups, for which no other theoretical explanation appears to exist. PMID- 26873264 TI - Erratum to: Impact of the Syrian Crisis on the Hospitalization of Syrians in a Psychiatric Setting. PMID- 26873265 TI - Pharmacophore generation, atom-based 3D-QSAR, HQSAR and activity cliff analyses of benzothiazine and deazaxanthine derivatives as dual A2A antagonists/MAO-B inhibitors. AB - Dual inhibition of A2A and MAO-B is an emerging strategy in neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, atom-based three-dimensional quantitative structure-activity relationship (3D-QSAR) and hologram quantitative structure-activity relationship (HQSAR) models were generated with benzothiazine and deazaxanthine derivatives. Based on activity against A2A and MAO-B, two statistically significant 3D-QSAR models (r2 = 0.96, q2 = 0.76 and r2 = 0.91, q2 = 0.63) and HQSAR models (r2 = 0.93, q2 = 0.68 and r2 = 0.97, q2 = 0.58) were developed. In an activity cliff analysis, structural outliers were identified by calculating the Mahalanobis distance for a pair of compounds with A2A and MAO-B inhibitory activities. The generated 3D-QSAR and HQSAR models, activity cliff analysis, molecular docking and dynamic studies for dual target protein inhibitors provide key structural scaffolds that serve as building blocks in designing drug-like molecules for neurodegenerative diseases. PMID- 26873266 TI - Microtensile strength of resin cement bond to indirect composite treated by different output powers of Er:YAG laser. AB - The study aimed to evaluate the effect of different output powers of Er:YAG laser on microtensile bonding strength of indirect composite to resin cements.36 indirect composite blocks (GC Gradia DA2, Japan) size 15 * 10 * 10 mm(3) were constructed, and divided into 12 groups, as follows:G1: control group (no treatment); Groups G2 to G6: treated with Er:YAG laser (2,940 nm) in noncontact mode, frequency 20 Hz, pulse duration 470 us, with output power ranging from 2W to 6W; Groups G7 sandblasting, Groups 8 to G12: as Groups G2 to G 6 with preparatory sandblasting. One specimen from each group was analyzed by SEM; each specimen was fixed to a specialized metal jig using cyanoacrylate (Mitreapel, Beta Kimya San. Ve TIC, Iran) and debonded under tension with a universal testing machine (Zwick, Germany) at a crosshead speed of 0.5 mm min(-1). Sandblasting and laser can improve bond strength above an energy level of 150 mJ. SEM evaluation of laser-treated specimens showed irregularities and deep undercuts. T test analysis showed no significant difference between sandblasted and non-sandblasted group, with laser output power of 0, 100, or 150 mJ (P = 0.666, P = 0.875, and P = .069); in the specimens irradiated with energy output of 200, 250, or 300 mJ, sandblasted specimens showed higher bond strength than non-sandblasted ones. The results demonstrate that, in composite resin irradiated with laser at energy output of 200-300 mJ, sandblasting might be a suitable procedure to enhance bond strength of resin cement. PMID- 26873268 TI - Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: the effect of index date selection? PMID- 26873267 TI - Epilepsy in young Tsc1(+/-) mice exhibits age-dependent expression that mimics that of human tuberous sclerosis complex. AB - OBJECTIVE: To describe the epileptic phenotype of Tsc1(+/-) mice pups in comparison with age-related seizures in human tuberous sclerosis complex (TSC). METHODS: Tsc1(+/-) and control mice underwent intracranial electroencephalography (EEG) recording at postnatal ages (P)8 to P33, with linear silicon probe implanted in the somatosensory cortex of one or both hemispheres for 8-24 h. Ictal events were classified visually by independent analyzers; distinct EEG patterns were related to age and analyzed to quantify field potential characteristics and signal dynamics between hemispheres. We collected retrospectively 20 infants with prenatally diagnosed TSC and EEG before seizure onset, and analyzed the electroclinical course of epilepsy, taking into account a first-line treatment by vigabatrin. RESULTS: Spontaneous seizures were disclosed in 55% of Tsc1(+/-) mice at P9-18. Three ictal patterns were identified: from P9 to P12 "spike clusters" consisted of recurring large spikes without clinical correlate; "spasm-like" discharges dominated from P13 to P16 consisting of high amplitude large field potential superimposed with or followed by fast activity repeated every 2-10 s for at least 20 s, accompanied by rhythmic limb contractions; from P14 to P18 a "tonic-clonic like" pattern comprised rhythmic spikes of increasing amplitude with tonic-clonic movements. Early onset "spike clusters" were mainly unilateral, whereas "spasm-like" and "tonic-clonic like" patterns were bilateral. Interhemispheric propagation was significantly faster for "tonic-clonic like" than for "spasm-like" events. In infants diagnosed prenatally with TSC, clusters of sharp waves or spikes preceded the first seizure, and vigabatrin prevented the development of seizures. Patients treated after seizure onset developed spasms or focal seizures that were pharmacoresistant in 66.7% of cases. SIGNIFICANCE: Tsc1(+/-) mice pups exhibit an age-dependent seizure pattern sequence mimicking early human TSC epilepsy features. Spike clusters before seizure onset in TSC should be considered as a first stage of epilepsy reinforcing the concept of preventive antiepileptic therapy. PMID- 26873269 TI - Potential confounding in colchicine and cardiovascular disease study. PMID- 26873270 TI - Effects of various stages of nephropathy on wound healing in patients with diabetes: an observational cohort study encompassing 731 diabetics. AB - BACKGROUND AND OBJECTIVE: In diabetics genetic predisposition, poor glycemic control and arterial hypertension contribute to nephropathy development in patients affected by diabetes mellitus. We set up the hypothesis that diabetic nephropathy and incisional hernia formation may have in common alterations of collagen composition and tested whether the occurrence of diabetic nephropathy coincides with wound healing disturbance (incisional herniation) or connective tissue diseases (inguinal herniation, umbilical herniation, aortic aneurysm, varicose veins, disc herniation). DESIGN: A questionnaire on surgical procedures, wound healing and connective tissue disorders was performed with 731 diabetics. Furthermore, test results for kidney function and damage (creatinine clearance, proteinuria) and blood sugar control (HbA1c) were recorded. Correlations between aforementioned connective tissue diseases and "advanced" diabetic nephropathy were calculated. "Advanced" diabetic nephropathy was assumed in patients with macroproteinuria, CKD stage 5 and/or end-stage renal disease. All diabetics with CKD stages 1 and 2 without proteinuria were included in the "control" group. A subgroup analysis on incisional hernia formation coinciding with diabetic nephropathy was performed in patients with previously performed abdominal surgery. RESULTS: In patients with advanced nephropathy, some diseases with connective tissue alterations, such as inguinal herniation, aortic aneurysms and varicose veins, did not occur more frequently than in patients without nephropathy. In diabetics with nephropathy, umbilical herniation (3 vs. 8.2 %, p = 0.04) and disc herniation rates (5.7 vs. 16.1 %, p = 0.002) were significantly lower. Subgroup analysis of patients with previously performed abdominal surgery (n = 381) revealed significantly higher incisional herniation rates when "advanced" diabetic nephropathy was present (16 % compared to 5.7 % without nephropathy, p = 0.016). CONCLUSION: Our findings support the hypothesis that incisional hernia formation and diabetic nephropathy are positively correlated. Conversely, umbilical and disc herniation pathomechanisms are distinct, as these negatively correlate with the presence of advanced diabetic nephropathy. PMID- 26873271 TI - Bayesian inference for latent biologic structure with determinantal point processes (DPP). AB - We discuss the use of the determinantal point process (DPP) as a prior for latent structure in biomedical applications, where inference often centers on the interpretation of latent features as biologically or clinically meaningful structure. Typical examples include mixture models, when the terms of the mixture are meant to represent clinically meaningful subpopulations (of patients, genes, etc.). Another class of examples are feature allocation models. We propose the DPP prior as a repulsive prior on latent mixture components in the first example, and as prior on feature-specific parameters in the second case. We argue that the DPP is in general an attractive prior model for latent structure when biologically relevant interpretation of such structure is desired. We illustrate the advantages of DPP prior in three case studies, including inference in mixture models for magnetic resonance images (MRI) and for protein expression, and a feature allocation model for gene expression using data from The Cancer Genome Atlas. An important part of our argument are efficient and straightforward posterior simulation methods. We implement a variation of reversible jump Markov chain Monte Carlo simulation for inference under the DPP prior, using a density with respect to the unit rate Poisson process. PMID- 26873272 TI - Neospora caninum seropositivity and reproductive risk factors in dogs. AB - Despite the importance of Neospora caninum in veterinary medicine, knowledge of distribution of neosporosis in dog populations in some countries is still poor. The aims of the present study were to determine the occurrence of anti-N. caninum antibodies in one-hundred dogs living in cattle farms or dog breedings in central Italy and to evaluate the risk factors associated with seropositivity. The incidence of reproductive system disorders (e.g. infertility after first pregnancy) was also evaluated. Serum from breeding and farm dogs was tested to an indirect immunofluorescent antibody test (IFAT) to assess the occurrence of seropositivity. Management and individual data were collected and analysed both by linear and logistic multiple-regression models to find reliable predictors of seroprevalence and anti-N. caninum antibody level. The seropositivity for N. caninum was 32%. Dogs reared for breeding and presence of cattle on the farm were associated with seropositivity for N. caninum. Dogs living in the cattle farms showed a higher seropositivity for N. caninum (46%) compared with those living in dogs breeding (18%) (P < 0.05). The high presence of seropositive dogs in cattle farms of the study region demonstrates the potential risk of horizontal transmission of N. caninum between dogs and cattle, regardless the occurrence of reproductive system disorders or with infectious bovine tissues contact. Although the Neospora seropositivity in dog breedings may appear relatively low if compared with that found in dogs living with livestock, this infection, apparently underestimated, should be considered as a potential serious problem in canine medicine. PMID- 26873273 TI - Echinococcus granulosus fatty acid binding proteins subcellular localization. AB - Two fatty acid binding proteins, EgFABP1 and EgFABP2, were isolated from the parasitic platyhelminth Echinococcus granulosus. These proteins bind fatty acids and have particular relevance in flatworms since de novo fatty acids synthesis is absent. Therefore platyhelminthes depend on the capture and intracellular distribution of host's lipids and fatty acid binding proteins could participate in lipid distribution. To elucidate EgFABP's roles, we investigated their intracellular distribution in the larval stage by a proteomic approach. Our results demonstrated the presence of EgFABP1 isoforms in cytosolic, nuclear, mitochondrial and microsomal fractions, suggesting that these molecules could be involved in several cellular processes. PMID- 26873274 TI - How to Determine if You Have Succeeded at Neurology Residency. PMID- 26873275 TI - The contribution of surprise to the prediction based modulation of fMRI responses. AB - In recent years, several functional magnetic resonance imaging (fMRI) studies showed that correct stimulus predictions reduce the neural responses when compared to surprising events (Egner et al., 2010). Further, it has been shown that such fulfilled expectations enhance the magnitude of repetition suppression (RS, i.e. a decreased neuronal response after the repetition of a given stimulus) in face selective visual cortex as well (Summerfield et al., 2008). Current MEG and neuroimaging studies suggest that the underlying mechanisms of expectation effects are independent from these of RS (Grotheer and Kovacs, 2015; Todorovic and Lange, 2012). However, it is not clear as of today how perceptual expectations modulate the neural responses: is the difference between correctly predicted and surprising stimuli due to a genuine response reduction for correctly predicted stimuli or is it due to an increased response for surprising stimuli? Therefore, here we used a modified version of the paradigm of Grotheer and Kovacs (2015) to induce predictions independently from repetition probability by presenting pairs of faces (female, male or infant) that were either repeated or alternating. Orthogonally to this, predictions were manipulated by the gender of the first face within each pair so that it signaled high, low or equal probability of repetitions. An unpredicted, neutral condition with equal probabilities for alternating and repeated trials was used to identify the role of surprising and enhancing modulations. Similarly, to Grotheer and Kovacs (2015), we found significant RS and significant expectation effect in the FFA. Importantly, we observed larger response for surprising events in comparison to the neutral and correctly predicted conditions for alternating trials. Altogether, these results emphasize the role of surprise in prediction effects. PMID- 26873276 TI - Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations. AB - BACKGROUND: Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. OBJECTIVES: The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. METHODS: This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of >=20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. RESULTS: Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). CONCLUSIONS: Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation. PMID- 26873277 TI - Tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual Hajj pilgrimage. AB - Tuberculosis (TB) is now the most common infectious cause of death worldwide. In 2014, an estimated 9.6 million people developed active TB. There were an estimated three million people with active TB including 360000 with multidrug resistant TB (MDR-TB) who were not diagnosed, and such people continue to fuel TB transmission in the community. Accurate data on the actual burden of TB and the transmission risk associated with mass gatherings are scarce and unreliable due to the small numbers studied and methodological issues. Every year, an estimated 10 million pilgrims from 184 countries travel to the Kingdom of Saudi Arabia (KSA) to perform the Hajj and Umrah pilgrimages. A large majority of pilgrims come from high TB burden and MDR-TB endemic areas and thus many may have undiagnosed active TB, sub-clinical TB, and latent TB infection. The Hajj pilgrimage provides unique opportunities for the KSA and the 184 countries from which pilgrims originate, to conduct high quality priority research studies on TB under the remit of the Global Centre for Mass Gatherings Medicine. Research opportunities are discussed, including those related to the definition of the TB burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual Hajj pilgrimage. The associated data are required to develop international recommendations and guidelines for TB management and control at mass gathering events. PMID- 26873278 TI - HIV in the MENA Region: Cultural and Political Challenges. PMID- 26873279 TI - Etiologic predictive value of a rapid immunoassay for the detection of group A Streptococcus antigen from throat swabs in patients presenting with a sore throat. AB - BACKGROUND: Clinical reasoning utilizing certain symptoms and scores has not proven to be a reliable decision-making tool to determine whether or not to suspect a group A Streptococcus (GAS) infection in the patient presenting with a sore throat. Culture as the so-called 'gold standard' is impracticable because it takes 1 to 2 days (and even longer in remote locations) for a result, and thus treatment decisions will be made without the result available. Rapid diagnostic antigen tests have demonstrated sufficient sensitivities and specificities in detecting GAS antigens to identify GAS throat infections. METHODS: Throat swab samples were collected from patients attending the Mount Isa Hospital emergency department for a sore throat; these samples were compared to swab samples collected from healthy controls who did not have a sore throat. Both groups were aged 3-15 years. All swab samples were analyzed with a point-of-care test (Alere Test Pack +Plus with OBC Strep A). The etiologic predictive value (EPV) of the throat swab was calculated. RESULTS: The 95% confidence interval for positive EPV was 88-100% and for negative EPV was 97-99%, depending on assumptions made. CONCLUSION: This study demonstrates that the point-of-care test Alere Test Pack +Plus Strep A has a high positive predictive value and is able to rule in GAS infection as long as the proportion of carriers is low. Also the negative predictive value for ruling out GAS as the etiologic agent is very high irrespective of the carrier rate. Hence, this test is always useful to rule out GAS infection. PMID- 26873280 TI - Being a gay man in Turkey: internalised sexual prejudice as a function of prevalent hegemonic masculinity perceptions. AB - This paper examines expressions and experiences of internalised sexual stigma with respect to definitions of masculinity and identity conflicts through a thematic analysis of life-history narratives of 14 self-identified gay men living in Turkey. The analysis reveals that internalised sexual prejudice emerges when widely accepted hegemonic masculinity ideology is 'violated' by being gay. Participants' narratives indicate that their construction of masculinity is a vigorous process established via encounters with hegemonic masculinity. Findings are discussed in the context of the relevant literature and in relation to Turkish culture's traditional understanding of gender and gender roles. PMID- 26873281 TI - Estimation of loads on human lumbar spine: A review of in vivo and computational model studies. AB - Spinal loads are recognized to play a causative role in back disorders and pain. Knowledge of lumbar spinal loads is required in proper management of various spinal disorders, effective risk prevention and assessment in the workplace, sports and rehabilitation, realistic testing of spinal implants as well as adequate loading in in vitro studies. During the last few decades, researchers have used a number of techniques to estimate spinal loads by measuring in vivo changes in the intradiscal pressure, body height, or forces and moments transmitted via instrumented vertebral implants. In parallel, computational models have been employed to estimate muscle forces and spinal loads under various static and dynamic conditions. Noteworthy is the increasing growth in latter computational investigations. This paper aims to review, compare and critically evaluate the existing literature on in vivo measurements and computational model studies of lumbar spinal loads to lay the foundation for future biomechanical studies. Towards this goal, the paper reviews in separate sections models dealing with static postures (standing, sitting, lying) as well as slow and fast dynamic activities (lifting, sudden perturbations and vibrations). The findings are helpful in many areas such as work place safety design and ergonomics, injury prevention, performance enhancement, implant design and rehabilitation management. PMID- 26873282 TI - Uncertainty quantification for personalized analyses of human proximal femurs. AB - Computational models for the personalized analysis of human femurs contain uncertainties in bone material properties and loads, which affect the simulation results. To quantify the influence we developed a probabilistic framework based on polynomial chaos (PC) that propagates stochastic input variables through any computational model. We considered a stochastic E-rho relationship and a stochastic hip contact force, representing realistic variability of experimental data. Their influence on the prediction of principal strains (epsilon1 and epsilon3) was quantified for one human proximal femur, including sensitivity and reliability analysis. Large variabilities in the principal strain predictions were found in the cortical shell of the femoral neck, with coefficients of variation of ~40%. Between 60 and 80% of the variance in epsilon1 and epsilon3 are attributable to the uncertainty in the E-rho relationship, while ~10% are caused by the load magnitude and 5-30% by the load direction. Principal strain directions were unaffected by material and loading uncertainties. The antero superior and medial inferior sides of the neck exhibited the largest probabilities for tensile and compression failure, however all were very small (pf<0.001). In summary, uncertainty quantification with PC has been demonstrated to efficiently and accurately describe the influence of very different stochastic inputs, which increases the credibility and explanatory power of personalized analyses of human proximal femurs. PMID- 26873283 TI - Valorisation of food waste via fungal hydrolysis and lactic acid fermentation with Lactobacillus casei Shirota. AB - Food waste recycling via fungal hydrolysis and lactic acid (LA) fermentation has been investigated. Hydrolysates derived from mixed food waste and bakery waste were rich in glucose (80.0-100.2gL(-1)), fructose (7.6gL(-1)) and free amino nitrogen (947-1081mgL(-1)). In the fermentation with Lactobacillus casei Shirota, 94.0gL(-1) and 82.6gL(-1) of LA were produced with productivity of 2.61gL(-1)h( 1) and 2.50gL(-1)h(-1) for mixed food waste and bakery waste hydrolysate, respectively. The yield was 0.94gg(-1) for both hydrolysates. Similar results were obtained using food waste powder hydrolysate, in which 90.1gL(-1) of LA was produced with a yield and productivity of 0.92gg(-1) and 2.50gL(-1)h(-1). The results demonstrate the feasibility of an efficient bioconversion of food waste to LA and a decentralized approach of food waste recycling in urban area. PMID- 26873284 TI - Enhancing biogas production from vinasse in sugarcane biorefineries: Effects of urea and trace elements supplementation on process performance and stability. AB - In this study, the effects of nitrogen, phosphate and trace elements supplementation were investigated in a semi-continuously operated upflow anaerobic sludge blanket system to enhance process stability and biogas production from sugarcane vinasse. Phosphate in form of KH2PO4 induced volatile fatty acids accumulation possibly due to potassium inhibition of the methanogenesis. Although nitrogen in form of urea increased the reactor's alkalinity, the process was overloaded with an organic loading rate of 6.1gCODL( 1)d(-1) and a hydraulic retention time of 3.6days. However, by supplementing urea and trace elements a stable operation even at an organic loading rate of 9.6gCODL(-1)d(-1) and a hydraulic retention time of 2.5days was possible, resulting in 79% higher methane production rate with a stable specific methane production of 239mLgCOD(-1). PMID- 26873285 TI - Aerobic granular processes: Current research trends. AB - Aerobic granules are large biological aggregates with compact interiors that can be used in efficient wastewater treatment. This mini-review presents new researches on the development of aerobic granular processes, extended treatments for complicated pollutants, granulation mechanisms and enhancements of granule stability in long-term operation or storage, and the reuse of waste biomass as renewable resources. A discussion on the challenges of, and prospects for, the commercialization of aerobic granular process is provided. PMID- 26873286 TI - Slow pyrolysis of prot, alkali and dealkaline lignins for production of chemicals. AB - Effect of different lignins were studied during slow pyrolysis. Maximum bio-oil yield of 31.2, 34.1, and 29.5wt.% was obtained at 350, 450 and 350 degrees C for prot lignin, alkali lignin and dealkaline lignin respectively. Maximum yield of phenolic compounds 78%, 80% and 92% from prot lignin, alkali and dealkaline lignin at 350, 450 and 350 degrees C. The differences in the pyrolysis products indicated the source of lignins such as soft and hard wood lignins. The biochar characterisation revealed that the various ether linkages were broken during pyrolysis and lignin was converted into monomeric substituted phenols. Bio-oil showed that the relative contents of each phenolic compound changes significantly with pyrolysis temperature and also the relative contents of each compound changes with different samples. PMID- 26873287 TI - New perspectives for the design of sustainable bioprocesses for phosphorus recovery from waste. AB - Phosphate rock has long been used for the production of phosphorus based chemicals. However, considering the depletion of the reservoirs and the decrease of the quality of phosphate rocks, a potential market is now emerging for the recovery of phosphate from waste and its reuse for different applications. Notably, phosphate recovery from wastewater could be included in a circular economy approach. This review focuses on the use of microbial systems for phosphorus accumulation and recovery, by considering the actual range of analytical techniques available for the monitoring of phosphorus accumulating organisms, as well as the actual biochemical and metabolic engineering toolbox available for the optimization of bioprocesses. In this context, knowledge gathered from process, system and synthetic biology could potentially lead to innovative process design. PMID- 26873289 TI - Alphablockers and risk of stroke. PMID- 26873288 TI - Optimization of 1,3-dihydroxyacetone production from crude glycerol by immobilized Gluconobacter oxydans MTCC 904. AB - This study has addressed the matter of optimization of production of the value added product, dihydroxyacetone, from crude glycerol using immobilized cells of Gluconobacter oxydans. Statistical optimization of the fermentation medium revealed MgSO4.7H2O, (NH4)2SO4 and KH2PO4 as the significant components, in addition to small concentration of yeast extract. As per previous literature, these components augment the activity of glycerol dehydrogenase enzyme in metabolism and provide assimilable nitrogen and sulfur source for cell growth. Yeast extract not only provides essential growth factors, but also accelerates production of alcohol dehydrogenase enzyme due to amino acids present. The DHA yield from crude glycerol (20g/L) with optimized medium is 14.08g/L, which is just 12% lower than the yield for pure glycerol .This study has thus established that proper optimization of fermentation medium reduces the adverse effect of impurities in crude glycerol on fermentation process and DHA yield. PMID- 26873290 TI - WITHDRAWN: Smoking cessation and the incidence of pre-diabetes and type 2 diabetes: A cohort study. AB - This article has been withdrawn at the request of the author(s) and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. PMID- 26873291 TI - Use of chromatin remodeling ATPases as RNAi targets for parental control of western corn rootworm (Diabrotica virgifera virgifera) and Neotropical brown stink bug (Euschistus heros). AB - RNA interference (RNAi) is a gene silencing mechanism that is present in animals and plants and is triggered by double stranded RNA (dsRNA) or small interfering RNA (siRNA), depending on the organism. In the western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), RNAi can be achieved by feeding rootworms dsRNA added to artificial diet or plant tissues transformed to express dsRNA. The effect of RNAi depends on the targeted gene function and can range from an absence of phenotypic response to readily apparent responses, including lethality. Furthermore, RNAi can directly affect individuals that consume dsRNA or the effect may be transferred to the next generation. Our previous work described the potential use of genes involved in embryonic development as a parental RNAi technology for the control of WCR. In this study, we describe the use of chromatin-remodeling ATPases as target genes to achieve parental gene silencing in two insect pests, a coleopteran, WCR, and a hemipteran, the Neotropical brown stink bug, Euschistus heros Fabricius (Hemiptera: Pentatomidae). Our results show that dsRNA targeting chromatin remodeling ATPase transcripts, brahma, mi-2, and iswi strongly reduced the fecundity of the exposed females in both insect species. Additionally, knockdown of chd1 reduced the fecundity of E. heros. PMID- 26873292 TI - Potential detoxification of gossypol by UDP-glycosyltransferases in the two Heliothine moth species Helicoverpa armigera and Heliothis virescens. AB - The cotton bollworm Helicoverpa armigera and the tobacco budworm Heliothis virescens are closely related generalist insect herbivores and serious pest species on a number of economically important crop plants including cotton. Even though cotton is well defended by its major defensive compound gossypol, a toxic sesquiterpene dimer, larvae of both species are capable of developing on cotton plants. In spite of severe damage larvae cause on cotton plants, little is known about gossypol detoxification mechanisms in cotton-feeding insects. Here, we detected three monoglycosylated and up to five diglycosylated gossypol isomers in the feces of H. armigera and H. virescens larvae fed on gossypol-supplemented diet. Candidate UDP-glycosyltransferase (UGT) genes of H. armigera were selected by microarray studies and in silico analyses and were functionally expressed in insect cells. In enzymatic assays, we show that UGT41B3 and UGT40D1 are capable of glycosylating gossypol mainly to the diglycosylated gossypol isomer 5 that is characteristic for H. armigera and is absent in H. virescens feces. In conclusion, our results demonstrate that gossypol is partially metabolized by UGTs via glycosylation, which might be a crucial step in gossypol detoxification in generalist herbivores utilizing cotton as host plant. PMID- 26873294 TI - Entrapment of a Pacing Lead within a Chiari Network: Utility of Intracardiac Echo and a Laser Sheath. AB - Although rare, Chiari networks are elaborate embryological remnants that can pose distinct challenges for catheter and pacing lead manipulation within the right atrium. Device entrapment may require open thoracotomy for removal, with significant morbidity. We report an unusual case of pacing lead entanglement within this structure, followed by prompt intracardiac echocardiographic identification and laser sheath removal. PMID- 26873293 TI - Provider Training to Screen and Initiate Evidence-Based Pediatric Obesity Treatment in Routine Practice Settings: A Randomized Pilot Trial. AB - INTRODUCTION: This randomized pilot trial evaluated two training modalities for first-line, evidence-based pediatric obesity services (screening and goal setting) among nursing students. METHOD: Participants (N = 63) were randomized to live interactive training or Web-facilitated self-study training. Pretraining, post-training, and 1-month follow-up assessments evaluated training feasibility, acceptability, and impact (knowledge and skill via simulation). Moderator (previous experience) and predictor (content engagement) analyses were conducted. RESULTS: Nearly all participants (98%) completed assessments. Both types of training were acceptable, with higher ratings for live training and participants with previous experience (ps < .05). Knowledge and skill improved from pretraining to post-training and follow-up in both conditions (ps < .001). Live training demonstrated greater content engagement (p < .01). CONCLUSIONS: The training package was feasible, acceptable, and efficacious among nursing students. Given that live training had higher acceptability and engagement and online training offers greater scalability, integrating interactive live training components within Web-based training may optimize outcomes, which may enhance practitioners' delivery of pediatric obesity services. PMID- 26873295 TI - Insights from the ganglionic acetylcholine receptor autoantibodies in patients with Sjogren's syndrome. AB - OBJECTIVE: It is not known whether autonomic neuropathy is a feature of Sjogren's syndrome (SS) or whether it is related to circulating antiganglionic acetylcholine receptor (gAChR) antibodies. The goal of the present study was to investigate the autonomic dysfunction in patients with SS and the associations between autonomic dysfunction, anti-gAChR antibodies, and clinical features of SS. METHODS: (1) The first observational study tested for the presence of gAChR antibodies in the serum samples from 39 patients with SS (absent information regarding autonomic symptoms) and healthy volunteers. (2) In the second study, serological and clinical data from 10 Japanese patients diagnosed with SS were reviewed. These patients showed autonomic dysfunction, and luciferase immunoprecipitation systems (LIPS) test was conducted to detect anti-alpha3 and anti-beta4 gAChR antibodies. (3) In the final analysis, we combined the data of seropositive SS patients with autonomic symptom from the first study with all of the patients from the second study, and analyzed the clinical features. RESULTS: (1) The LIPS assay revealed that anti-gAChRalpha3 and anti-gAChRbeta4 antibodies were detected in the sera from patients with SS (23.1%, 9/39). Five of nine SS patients had autonomic symptoms. (2) Anti-alpha3 and anti-beta4 gAChR antibodies were also detected in 80.0% (8/10) of patients with SS with autonomic symptoms. Six of the ten patients were diagnosed as having SS after neurological symptoms developed. These seropositive patients had predominant and severe autonomic symptoms and were diagnosed with autonomic neuropathy. (3) Thirteen of fifteen SS patients with autonomic symptoms (86.7%) were seropositive for anti-gAChR antibodies, and we confirmed sicca complex, orthostatic hypotension, upper and lower gastrointestinal (GI) symptoms, and bladder dysfunction at high rates. CONCLUSION: The present results suggest the possibility of anti-gAChR antibodies aiding the diagnostics of SS with autonomic dysfunction. PMID- 26873296 TI - Deep dermal fungal infection in an Asian renal transplant recipient. PMID- 26873297 TI - Neuroendocrine tumor of the common bile duct. PMID- 26873301 TI - Subcutaneous flexor tendon rupture in patients with rheumatoid arthritis. AB - OBJECTIVE: We examined the clinical features and functional outcomes of surgically repaired subcutaneous flexor tendon ruptures in patients with rheumatoid arthritis (RA). METHODS: This retrospective study included 41 fingers of 24 RA patients who underwent surgical treatment for flexor tendon ruptures. Evaluations performed at the time of presentation following rupture were C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score in 28 joints (DAS28)-ESR, as well as Larsen grading for carpal bone destruction. The ruptured tendon and postoperative active range of motion (ROM) of digits were also examined. RESULTS: The mean CRP was 2.4 mg/dl, ESR was 52 mm/h, and the DAS28-ESR was 4.5. Carpal bone destruction according to Larsen grade IV-V was observed in 18/24 patients. Affected digits were most commonly the thumb (12) and the ring and little fingers (9 each). Tendon ruptures were most common in the carpal tunnel in zone IV. The mean postoperative finger ROM (flexion/extension) was 38 degrees /2 degrees for the interphalangeal (IP) joint of the thumb and 23 degrees /-2 degrees for the distal interphalangeal joint of the other four fingers. CONCLUSIONS: Patients with flexor tendon ruptures present with high disease activity and advanced bone destruction. It is important to reduce the risk of progressive bone destruction and subsequent tendon rupture via tight control of disease activity. PMID- 26873302 TI - Memory for faces with emotional expressions in Alzheimer's disease and healthy older participants: positivity effect is not only due to familiarity. AB - Young individuals better memorize initially seen faces with emotional rather than neutral expressions. Healthy older participants and Alzheimer's disease (AD) patients show better memory for faces with positive expressions. The socioemotional selectivity theory postulates that this positivity effect in memory reflects a general age-related preference for positive stimuli, subserving emotion regulation. Another explanation might be that older participants use compensatory strategies, often considering happy faces as previously seen. The question about the existence of this effect in tasks not permitting such compensatory strategies is still open. Thus, we compared the performance of healthy participants and AD patients for positive, neutral, and negative faces in such tasks. Healthy older participants and AD patients showed a positivity effect in memory, but there was no difference between emotional and neutral faces in young participants. Our results suggest that the positivity effect in memory is not entirely due to the sense of familiarity for smiling faces. PMID- 26873303 TI - Do accelerometers mounted on the back provide a good estimate of impact loads in jumping and landing tasks? AB - Artistic gymnasts are frequently exposed to both low- and high-magnitude loads through impacts with the apparatus. These impact loads are thought to be associated with the high injury rates observed in gymnastics. Due to the variable apparatus and surfaces in gymnastics, impact loads during training are difficult to quantify. This study aimed to use triaxial accelerometers mounted on the back to assess impact loading during jumping and landing tasks. Twelve participants were fitted with an accelerometer on their upper and lower back, before performing a continuous hopping task, as well as drop landings and rebound jumps from various heights (37.5, 57.5, and 77.5 cm) onto a force platform. Peak resultant acceleration (PRA) was low-pass filtered with four cut-off frequencies (8, 15, 20, and 50 Hz). Filtering of PRA with the 20 Hz cut-off frequency showed the highest correlations between ground reaction force (GRF) and PRA. PRA recorded at the upper back, filtered with a 20 Hz cut-off frequency, appears to provide a good estimate of impact loading for continuous hopping and rebound jumps, but less so for drop landings since correlations between GRF and PRA were only significant when landing from 57.5 cm. PMID- 26873304 TI - Treatment of advanced soft tissue sarcoma: efficacy and safety of trabectedin, a multitarget agent, and update on other systemic therapeutic options. AB - Soft tissue sarcomas (STS) are rare mesenchymal cancers. Despite optimal management, nearly 50% of patients with localized disease will develop recurrence. The outcome for patients with metastatic STS is poor. There are few systemic treatment options available in this setting. Doxorubicin, with or without ifosfamide, is considered standard first line therapy. Some clinical trials have confirmed the activity of trabectedin as an effective and tolerable option for adult patients previously treated with doxorubicin and ifosfamide. Trabectedin was approved in the European Union and other countries based on the results of a randomized phase II trial involving patients with advanced liposarcoma and leiomyosarcoma receiving one of two different schedules of trabectedin. Recently a multicentre phase III trial randomized liposarcoma and leiomyosarcoma patients to receive either trabectedin or dacarbazine, demonstrating a significantly improved progression-free survival for patients treated with trabectedin compared to dacarbazine. We herein review the evidence for the use of trabectedin in adult advanced soft tissue sarcoma. PMID- 26873305 TI - The influence of space and time on the evolution of altruistic defence: the case of ant slave rebellion. AB - How can antiparasite defence traits evolve even if they do not directly benefit their carriers? An example of such an indirect defence is rebellion of enslaved Temnothorax longispinosus ant workers against their social parasite Temnothorax americanus, a slavemaking ant. Ant slaves have been observed to kill their oppressors' offspring, a behaviour from which the sterile slaves cannot profit directly. Parasite brood killing could, however, reduce raiding pressure on related host colonies nearby. We analyse with extensive computer simulations for the Temnothorax slavemaker system under what conditions a hypothetical rebel allele could invade a host population, and in particular, how host-parasite dynamics and population structure influence the rebel allele's success. Exploring a wide range of model parameters, we only found a small number of parameter combinations for which kin selection or multilevel selection could allow a slave rebellion allele to spread in the host population. Furthermore, we did not detect any cases in which the reduction of raiding pressure in the close vicinity of the slavemaker nest would substantially contribute to the inclusive fitness of rebels. This suggests that slave rebellion is not costly and perhaps a side effect of some other beneficial trait. In some of our simulations, however, even a costly rebellion allele could spread in the population. This was possible when host-parasite interactions led to a metapopulation dynamic with frequent local extinctions and recolonizations of demes by the offspring of few immigrants. PMID- 26873308 TI - Vitamin D levels in primary growth hormone deficiency disorder Prader-Willi syndrome. PMID- 26873306 TI - Malignant pleural mesothelioma: an update on diagnosis and treatment options. AB - Malignant pleural mesothelioma (MPM) represents a significant diagnostic and therapeutic challenge and is almost always a fatal disease. Imaging abnormalities are common, but have a limited role in distinguishing mesothelioma from metastatic pleural disease. Similarly, minimally invasive biomarkers have shown promise but also have limitations in the diagnosis of mesothelioma. In experienced centers, cytology and immunohistochemistry are now sufficient to diagnose the epithelioid subtype of mesothelioma, which can reduce the need for more invasive diagnostic investigations. Prognosis of MPM is modestly impacted by oncological treatments. Chemotherapy with cisplatin and pemetrexed is considered the standard of care, though the addition of bevacizumab to the platinum doublet may be the new standard of care. New targeted therapies have demonstrated some promise and are being addressed in clinical trials. This review focuses on the current data on the diagnostic and therapeutic issues of MPM. PMID- 26873307 TI - Differentiation of epithelial ovarian cancer subtypes by use of imaging and clinical data: a detailed analysis. AB - BACKGROUND: Primary epithelial ovarian carcinoma is sub-classified into serous, mucinous, endometrioid and clear cell subtypes. Neoadjuvant chemotherapy has become an alternative treatment option past several years, as serous carcinoma, the most common subtype, is known as chemotherapy-sensitive tumor. On the other hand, mucinous and clear cell carcinoma are known as chemotherapy-resistive. Therefore, it may be meaningful to estimate subtype of ovarian carcinoma using imaging modality. The purpose of this study is to study whether CT or MRI can determine the subtypes of epithelial ovarian cancers. METHODS: The imaging and clinical findings obtained from 125 consecutive patients with primary ovarian carcinoma were retrospectively analyzed. Forty-four of the patients had serous carcinoma; 13, mucinous carcinoma; 53, clear cell carcinoma; and 15, endometrioid carcinoma. We studied the bilateralism, morphological type, tumor diameter, solid portion ratio, relative signal intensity on T2WI and DWI, contrast ratio, and endometriosis on MRI and the calcification, peritoneal dissemination and lymph node metastasis, clinical staging, and thromboembolism on CT. We also studied the tumor markers and serum calcium concentrations. Each parameter was statistically analyzed by univariate and multivariate analyses. RESULTS: Serous carcinoma showed a significantly higher incidence of bilateral disease, smaller tumor size, higher signal intensity on DWI, and less frequent hypercalcemia. The CA19-9 level was significantly higher in mucinous carcinoma, in which most of the tumors appeared as multilocular cystic masses. Clear cell carcinoma appeared as unilateral disease with a larger solid portion and hypercalcemia in younger patients. Endometrioid carcinoma only showed a lower incidence of intraperitoneal dissemination. CONCLUSIONS: CT and MRI combined with clinical data especially tumor markers and presence of paraneoplastic syndrome could partly predict epithelial ovarian cancer subtypes. PMID- 26873309 TI - Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing's syndrome. AB - CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9beta (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing's syndrome (CS). DESIGN AND SETTING: Cross-sectional case-control study. PATIENTS AND METHODS: Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated. MAIN OUTCOME MEASURES: Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors. RESULTS: This study shows that carriers of the 9beta polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers. CONCLUSIONS: The 9beta and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism. PMID- 26873310 TI - Thyroid ultrasonography for personalized approach at thyroid nodules. PMID- 26873311 TI - Direct and Indirect Horizontal Transmission of the Antifungal Probiotic Bacterium Janthinobacterium lividum on Green Frog (Lithobates clamitans) Tadpoles. AB - Amphibian populations worldwide are being threatened by the disease chytridiomycosis, which is caused by Batrachochytrium dendrobatidis To mitigate the effects of B. dendrobatidis, bioaugmentation of antifungal bacteria has been shown to be a promising strategy. One way to implement bioaugmentation is through indirect horizontal transmission, defined as the transfer of bacteria from a host to the environment and to another host. In addition, direct horizontal transmission among individuals can facilitate the spread of a probiotic in a population. In this study, we tested whether the antifungal bacterium Janthinobacterium lividum could be horizontally transferred, directly or indirectly, in a laboratory experiment using Lithobates clamitans tadpoles. We evaluated the ability of J. lividumto colonize the tadpoles' skin and to persist through time using culture-dependent and culture-independent techniques. We also tested whether the addition of J. lividum affected the skin community in L. clamitans tadpoles. We found that transmission occurred rapidly by direct and indirect horizontal transmission, but indirect transmission that included a potential substrate was more effective. Even though J. lividum colonized the skin, its relative abundance on the tadpole skin decreased over time. The inoculation of J. lividum did not significantly alter the skin bacterial diversity of L. clamitans tadpoles, which was dominated by Pseudomonas Our results show that indirect horizontal transmission can be an effective bioaugmentation method. Future research is needed to determine the best conditions, including the presence of substrates, under which a probiotic can persist on the skin so that bioaugmentation becomes a successful strategy to mitigate chytridiomycosis. PMID- 26873312 TI - The Histone-Like Nucleoid Structuring Protein (H-NS) Is a Negative Regulator of the Lateral Flagellar System in the Deep-Sea Bacterium Shewanella piezotolerans WP3. AB - Although the histone-like nucleoid structuring protein (H-NS) is well known for its involvement in the adaptation of mesophilic bacteria, such as Escherichia coli, to cold environments and high-pressure stress, an understanding of the role of H-NS in the cold-adapted benthic microorganisms that live in the deep-sea ecosystem, which covers approximately 60% of the earth's surface, is still lacking. In this study, we characterized the function of H-NS in Shewanella piezotolerans WP3, which was isolated from West Pacific sediment at a depth of 1,914 m. Anhns gene deletion mutant (WP3Deltahns) was constructed, and comparative whole-genome microarray analysis was performed. H-NS had a significant influence (fold change, >2) on the expression of a variety of WP3 genes (274 and 280 genes were upregulated and downregulated, respectively), particularly genes related to energy production and conversion. Notably, WP3Deltahnsexhibited higher expression levels of lateral flagellar genes than WP3 and showed enhanced swarming motility and lateral flagellar production compared to those of WP3. The DNA gel mobility shift experiment showed that H-NS bound specifically to the promoter of lateral flagellar genes. Moreover, the high affinity binding sequences of H-NS were identified by DNase I protection footprinting, and the results support the "binding and spreading" model for H-NS functioning. To our knowledge, this is the first attempt to characterize the function of the universal regulator H-NS in a deep-sea bacterium. Our data revealed that H-NS has a novel function as a repressor of the expression of genes related to the energy-consuming secondary flagellar system and to swarming motility. PMID- 26873314 TI - Germs within Worms: Localization of Neorickettsia sp. within Life Cycle Stages of the Digenean Plagiorchis elegans. AB - Neorickettsia spp. are bacterial endosymbionts of parasitic flukes (Digenea) that also have the potential to infect and cause disease (e.g., Sennetsu fever) in the vertebrate hosts of the fluke. One of the largest gaps in our knowledge of Neorickettsia biology is the very limited information available regarding the localization of the bacterial endosymbiont within its digenean host. In this study, we used indirect immunofluorescence microscopy to visualize Neorickettsia sp. within several life cycle stages of the digenean Plagiorchis elegans Individual sporocysts, cercariae, metacercariae, and adults of P. elegans naturally infected with Neorickettsia sp. were obtained from our laboratory maintained life cycle, embedded, sectioned, and prepared for indirect immunofluorescence microscopy using anti-Neorickettsia risticiihorse serum as the primary antibody. Neorickettsiasp. was found within the tegument of sporocysts, throughout cercarial embryos (germ balls) and fully formed cercariae (within the sporocysts), throughout metacercariae, and within the tegument, parenchyma, vitellaria, uteri, testes, cirrus sacs, and eggs of adults. Interestingly, Neorickettsia sp. was not found within the ovarian tissue. This suggests that vertical transmission of Neorickettsia within adult digeneans occurs via the incorporation of infected vitelline cells into the egg rather than direct infection of the ooplasm of the oocyte, as has been described for other bacterial endosymbionts of invertebrates (e.g.,Rickettsia and Wolbachia). PMID- 26873313 TI - Direct Comparison of Physical Properties of Bacillus subtilis NCIB 3610 and B-1 Biofilms. AB - Many bacteria form surface-attached communities known as biofilms. Due to the extreme resistance of these bacterial biofilms to antibiotics and mechanical stresses, biofilms are of growing interest not only in microbiology but also in medicine and industry. Previous studies have determined the extracellular polymeric substances present in the matrix of biofilms formed by Bacillus subtilis NCIB 3610. However, studies on the physical properties of biofilms formed by this strain are just emerging. In particular, quantitative data on the contributions of biofilm matrix biopolymers to these physical properties are lacking. Here, we quantitatively investigated three physical properties of B. subtilis NCIB 3610 biofilms: the surface roughness and stiffness and the bulk viscoelasticity of these biofilms. We show how specific biomolecules constituting the biofilm matrix formed by this strain contribute to those biofilm properties. In particular, we demonstrate that the surface roughness and surface elasticity of 1-day-old NCIB 3610 biofilms are strongly affected by the surface layer protein BslA. For a second strain,B. subtilis B-1, which forms biofilms containing mainly gamma-polyglutamate, we found significantly different physical biofilm properties that are also differently affected by the commonly used antibacterial agent ethanol. We show that B-1 biofilms are protected from ethanol induced changes in the biofilm's stiffness and that this protective effect can be transferred to NCIB 3610 biofilms by the sole addition of gamma-polyglutamate to growing NCIB 3610 biofilms. Together, our results demonstrate the importance of specific biofilm matrix components for the distinct physical properties of B. subtilis biofilms. PMID- 26873315 TI - Use of Metagenomic Shotgun Sequencing Technology To Detect Foodborne Pathogens within the Microbiome of the Beef Production Chain. AB - Foodborne illnesses associated with pathogenic bacteria are a global public health and economic challenge. The diversity of microorganisms (pathogenic and nonpathogenic) that exists within the food and meat industries complicates efforts to understand pathogen ecology. Further, little is known about the interaction of pathogens within the microbiome throughout the meat production chain. Here, a metagenomic approach and shotgun sequencing technology were used as tools to detect pathogenic bacteria in environmental samples collected from the same groups of cattle at different longitudinal processing steps of the beef production chain: cattle entry to feedlot, exit from feedlot, cattle transport trucks, abattoir holding pens, and the end of the fabrication system. The log read counts classified as pathogens per million reads for Salmonella enterica,Listeria monocytogenes,Escherichia coli,Staphylococcus aureus, Clostridium spp. (C. botulinum and C. perfringens), and Campylobacter spp. (C. jejuni,C. coli, and C. fetus) decreased over subsequential processing steps. Furthermore, the normalized read counts for S. enterica,E. coli, and C. botulinumwere greater in the final product than at the feedlots, indicating that the proportion of these bacteria increased (the effect on absolute numbers was unknown) within the remaining microbiome. From an ecological perspective, data indicated that shotgun metagenomics can be used to evaluate not only the microbiome but also shifts in pathogen populations during beef production. Nonetheless, there were several challenges in this analysis approach, one of the main ones being the identification of the specific pathogen from which the sequence reads originated, which makes this approach impractical for use in pathogen identification for regulatory and confirmation purposes. PMID- 26873316 TI - Rapid Detection of Viable Bacillus anthracis Spores in Environmental Samples by Using Engineered Reporter Phages. AB - Bacillus anthracis, the causative agent of anthrax, was utilized as a bioterrorism agent in 2001 when spores were distributed via the U.S. postal system. In responding to this event, the Federal Bureau of Investigation used traditional bacterial culture viability assays to ascertain the extent of contamination of the postal facilities within 24 to 48 h of environmental sample acquisition. Here, we describe a low-complexity, second-generation reporter phage assay for the rapid detection of viableB. anthracis spores in environmental samples. The assay uses an engineered B. anthracis reporter phage (Wbeta::luxAB 2) which transduces bioluminescence to infected cells. To facilitate low-level environmental detection and maximize the signal response, expression of luxABin an earlier version of the reporter phage (Wbeta::luxAB-1) was optimized. These alterations prolonged signal kinetics, increased light output, and improved assay sensitivity. Using Wbeta::luxAB-2, detection of B. anthracis spores was 1 CFU in 8 h from pure cultures and as low as 10 CFU/g in sterile soil but increased to 10(5)CFU/g in unprocessed soil due to an unstable signal and the presence of competing bacteria. Inclusion of semiselective medium, mediated by a phage expressed antibiotic resistance gene, maintained signal stability and enabled the detection of 10(4)CFU/g in 6 h. The assay does not require spore extraction and relies on the phage infecting germinating cells directly in the soil sample. This reporter phage displays promise for the rapid detection of low levels of spores on clean surfaces and also in grossly contaminated environmental samples from complex matrices such as soils. PMID- 26873317 TI - Activities of Secreted Aryl Alcohol Quinone Oxidoreductases from Pycnoporus cinnabarinus Provide Insights into Fungal Degradation of Plant Biomass. AB - Auxiliary activities family 3 subfamily 2 (AA3_2) from the CAZy database comprises various functions related to ligninolytic enzymes, such as fungal aryl alcohol oxidases (AAO) and glucose oxidases, both of which are flavoenzymes. The recent study of the Pycnoporus cinnabarinus CIRM BRFM 137 genome combined with its secretome revealed that four AA3_2 enzymes are secreted during biomass degradation. One of these AA3_2 enzymes, scf184803.g17, has recently been produced heterologously in Aspergillus niger Based on the enzyme's activity and specificity, it was assigned to the glucose dehydrogenases (PcinnabarinusGDH [PcGDH]). Here, we analyze the distribution of the other three AA3_2 enzymes (scf185002.g8, scf184611.g7, and scf184746.g13) to assess their putative functions. These proteins showed the highest homology with aryl alcohol oxidase from Pleurotus eryngii Biochemical characterization demonstrated that they were also flavoenzymes harboring flavin adenine dinucleotide (FAD) as a cofactor and able to oxidize a wide variety of phenolic and nonphenolic aryl alcohols and one aliphatic polyunsaturated primary alcohol. Though presenting homology with fungal AAOs, these enzymes exhibited greater efficiency in reducing electron acceptors (quinones and one artificial acceptor) than molecular oxygen and so were defined as aryl-alcohol:quinone oxidoreductases (AAQOs) with two enzymes possessing residual oxidase activity (PcAAQO2 and PcAAQO3). Structural comparison of PcAAQO homology models with P. eryngii AAO demonstrated a wider substrate access channel connecting the active-site cavity to the solvent, explaining the absence of activity with molecular oxygen. Finally, the ability of PcAAQOs to reduce radical intermediates generated by laccase from P. cinnabarinus was demonstrated, shedding light on the ligninolytic system of this fungus. PMID- 26873318 TI - Systematic Mutational Analysis of Histidine Kinase Genes in the Nosocomial Pathogen Stenotrophomonas maltophilia Identifies BfmAK System Control of Biofilm Development. AB - The Gram-negative bacterium Stenotrophomonas maltophilialives in diverse ecological niches. As a result of its formidable capabilities of forming biofilm and its resistance to multiple antibiotic agents, the bacterium is also a nosocomial pathogen of serious threat to the health of patients whose immune systems are suppressed or compromised. Besides the histidine kinase RpfC, the two component signal transduction system (TCS), which is the canonical regulatory machinery used by most bacterial pathogens, has never been experimentally investigated inS. maltophilia Here, we annotated 62 putative histidine kinase genes in the S. maltophilia genome and successfully obtained 51 mutants by systematical insertional inactivation. Phenotypic characterization identified a series of mutants with deficiencies in bacterial growth, swimming motility, and biofilm development. A TCS, named here BfmA-BfmK (Smlt4209-Smlt4208), was genetically confirmed to regulate biofilm formation inS. maltophilia Together with interacting partner prediction and chromatin immunoprecipitation screens, six candidate promoter regions bound by BfmA in vivo were identified. We demonstrated that, among them, BfmA acts as a transcription factor that binds directly to the promoter regions of bfmA-bfmK and Smlt0800(acoT), a gene encoding an acyl coenzyme A thioesterase that is associated with biofilm development, and positively controls their transcription. Genome-scale mutational analyses of histidine kinase genes and functional dissection of BfmK-BfmA regulation in biofilm provide genetic information to support more in-depth studies on cellular signaling inS. maltophilia, in the context of developing novel approaches to fight this important bacterial pathogen. PMID- 26873320 TI - Killing of Staphylococcus aureus via Magnetic Hyperthermia Mediated by Magnetotactic Bacteria. AB - Staphylococcus aureus is a common hospital and household pathogen. Given the emergence of antibiotic-resistant derivatives of this pathogen resulting from the use of antibiotics as general treatment, development of alternative therapeutic strategies is urgently needed. Here, we assess the feasibility of killing S. aureus cells in vitro and in vivo through magnetic hyperthermia mediated by magnetotactic bacteria that possess magnetic nanocrystals and demonstrate magnetically steered swimming. The S. aureus suspension was added to magnetotactic MO-1 bacteria either directly or after coating with anti-MO-1 polyclonal antibodies. The suspensions were then subjected to an alternating magnetic field (AMF) for 1 h. S. aureus viability was subsequently assessed through conventional plate counting and flow cytometry. We found that approximately 30% of the S. aureus cells mixed with uncoated MO-1 cells were killed after AMF treatment. Moreover, attachment between the magnetotactic bacteria and S. aureus increased the killing efficiency of hyperthermia to more than 50%. Using mouse models, we demonstrated that magnetic hyperthermia mediated by antibody-coated magnetotactic MO-1 bacteria significantly improved wound healing. These results collectively demonstrated the effective eradication of S. aureus both in vitro and in vivo, indicating the potential of magnetotactic bacterium-mediated magnetic hyperthermia as a treatment for S. aureus-induced skin or wound infections. PMID- 26873319 TI - SaxA-Mediated Isothiocyanate Metabolism in Phytopathogenic Pectobacteria. AB - Pectobacteria are devastating plant pathogens that infect a large variety of crops, including members of the family Brassicaceae. To infect cabbage crops, these plant pathogens need to overcome the plant's antibacterial defense mechanisms, where isothiocyanates are liberated by hydrolysis of glucosinolates. Here, we found that a Pectobacterium isolate from the gut of cabbage root fly larvae was particularly resistant to isothiocyanate and even seemed to benefit from the abundant Brassica root metabolite 2-phenylethyl isothiocyanate as a nitrogen source in an ecosystem where nitrogen is scarce. The Pectobacterium isolate harbored a naturally occurring mobile plasmid that contained a sax operon. We hypothesized that SaxA was the enzyme responsible for the breakdown of 2-phenylethyl isothiocyanate. Subsequently, we heterologously produced and purified the SaxA protein and characterized the recombinant enzyme. It hydrolyzed 2-phenylethyl isothiocyanate to yield the products carbonyl sulfide and phenylethylamine. It was also active toward another aromatic isothiocyanate but hardly toward aliphatic isothiocyanates. It belongs to the class B metal dependent beta-lactamase fold protein family but was not, however, able to hydrolyze beta-lactam antibiotics. We discovered that several copies of the saxA gene are widespread in full and draft Pectobacterium genomes and therefore hypothesize that SaxA might be a new pathogenicity factor of the genus Pectobacterium, possibly compromising food preservation strategies using isothiocyanates. PMID- 26873321 TI - Genetic Diversity of Campylobacter jejuni and Campylobacter coli Isolates from Conventional Broiler Flocks and the Impacts of Sampling Strategy and Laboratory Method. AB - The genetic diversity of Campylobacter jejuni and Campylobacter coliisolates from commercial broiler farms was examined by multilocus sequence typing (MLST), with an assessment of the impact of the sample type and laboratory method on the genotypes of Campylobacter isolated. A total of 645C. jejuniand 106C. coli isolates were obtained from 32 flocks and 17 farms, with 47 sequence types (STs) identified. The Campylobacter jejuniisolates obtained by different sampling approaches and laboratory methods were very similar, with the same STs identified at similar frequencies, and had no major effect on the genetic profile of Campylobacter population in broiler flocks at the farm level. ForC. coli, the results were more equivocal. While some STs were widely distributed within and among farms and flocks, analysis of molecular variance (AMOVA) revealed a high degree of genetic diversity among farms forC. jejuni, where farm effects accounted for 70.5% of variance, and among flocks from the same farm (9.9% of variance for C. jejuni and 64.1% forC. coli). These results show the complexity of the population structure of Campylobacterin broiler production and that commercial broiler farms provide an ecological niche for a wide diversity of genotypes. The genetic diversity of C. jejuni isolates among broiler farms should be taken into account when designing studies to understand Campylobacter populations in broiler production and the impact of interventions. We provide evidence that supports synthesis of studies on C. jejuni populations even when laboratory and sampling methods are not identical. PMID- 26873322 TI - Alpha- and Gammaproteobacterial Methanotrophs Codominate the Active Methane Oxidizing Communities in an Acidic Boreal Peat Bog. AB - The objective of this study was to characterize metabolically active, aerobic methanotrophs in an ombrotrophic peatland in the Marcell Experimental Forest, in Minnesota. Methanotrophs were investigated in the field and in laboratory incubations using DNA-stable isotope probing (SIP), expression studies on particulate methane monooxygenase (pmoA) genes, and amplicon sequencing of 16S rRNA genes. Potential rates of oxidation ranged from 14 to 17 MUmol of CH4g dry weight soil(-1)day(-1) Within DNA-SIP incubations, the relative abundance of methanotrophs increased from 4% in situ to 25 to 36% after 8 to 14 days. Phylogenetic analysis of the(13)C-enriched DNA fractions revealed that the active methanotrophs were dominated by the genera Methylocystis(type II;Alphaproteobacteria),Methylomonas, and Methylovulum(both, type I;Gammaproteobacteria). In field samples, a transcript-to-gene ratio of 1 to 2 was observed for pmoA in surface peat layers, which attenuated rapidly with depth, indicating that the highest methane consumption was associated with a depth of 0 to 10 cm. Metagenomes and sequencing of cDNA pmoA amplicons from field samples confirmed that the dominant active methanotrophs were Methylocystis and Methylomonas Although type II methanotrophs have long been shown to mediate methane consumption in peatlands, our results indicate that members of the genera Methylomonas and Methylovulum(type I) can significantly contribute to aerobic methane oxidation in these ecosystems. PMID- 26873323 TI - Bacterial Succession in the Broiler Gastrointestinal Tract. AB - A feeding trial was performed with broilers receiving a diet of wheat-based feed (WBF), maize-based feed (MBF), or maize-based concentrates supplemented with 15% or 30% crimped kernel maize silage (CKMS-15 or CKMS-30, respectively). The aim of the study was to investigate the bacterial community compositions of the crop, gizzard, ileum, and cecum contents in relation to the feeding strategy and age (8, 15, 22, 25, 29, or 36 days). Among the four dietary treatments, bacterial diversity was analyzed for MBF and CKMS-30 by 454 pyrosequencing of the 16S rRNA gene. Since the diets had no significant influence on bacterial diversity, data were pooled for downstream analysis. With increasing age, a clear succession of bacterial communities and increased bacterial diversity were observed.Lactobacillaceae(belonging mainly to the genus Lactobacillus) represented most of the Firmicutesat all ages and in all segments of the gut except the cecum. The development of a "mature" microbiota in broilers occurred during the period from days 15 to 22. Striking increases in the relative abundances of Lactobacillus salivarius(17 to 36%) and clostridia (11 to 18%), and a concomitant decrease in the relative abundance of Lactobacillus reuteri, were found in the ileum after day 15. The concentration of deconjugated bile salts increased in association with the increased populations of L. salivarius and clostridia. Both L. salivarius and clostridia deconjugate bile acids, and increases in the abundances of these bacteria might be associated with growth reduction and gastrointestinal (GI) disorders occurring in the critical period of broiler life between days 20 and 30. PMID- 26873326 TI - Thermithiobacillus plumbiphilus sp. nov., a sulfur-oxidizing bacterium isolated from lead sulfide. AB - A novel sulfur oxidizer, strain wk12T, was isolated from an industrially synthesized lead (II) sulfide. The G+C content of the genomic DNA was around 58.5 mol%. The major components in the cellular fatty acid profile were summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), C16 : 0 and summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c). The strain oxidized lead sulfide, thiosulfate and tetrathionate as electron donors to support autotrophic growth. Cells of strain wk12T were motile, rod-shaped (0.5-1.0 * 0.7-2.2 MUm), and Gram-stain negative. For growth, the temperature range was 5-37 degrees C, and optimum growth was observed at 28-32 degrees C. The pH range for growth was 5.8-8.7, with optimum growth at pH 6.4-7.1. Optimum growth of the isolate was observed in medium without NaCl, and no growth was observed in the medium containing 0.5 M or more NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the class Acidithiobacillia. The closest relative with a validly published name was Thermithiobacillus tepidarius DSM 3134T, with a 16S rRNA gene sequence similarity of 96 %. On the basis of phylogenetic and phenotypic properties, strain wk12T represents a novel species of the genus Thermithiobacillus, for which the name Thermithiobacillus plumbiphilus sp. nov. is proposed. The type strain is wk12T ( = NBRC 111508T = DSM 101799T). PMID- 26873324 TI - Gene expression identifies heterogeneity of metastatic behavior among gastrointestinal stromal tumors. AB - BACKGROUND: Adjuvant imatinib is useful in patients with gastrointestinal stromal tumors (GIST) at high risk of recurrence. At present, the risk of recurrence is determined based on tumor size, mitotic rate, tumor site, and tumor rupture. Previous studies using various biochemical pathways identified gene expression patterns that distinguish two subsets of aggressive fibromatosis (AF), serous ovarian carcinoma (OVCA), and clear cell renal cell carcinoma (RCC). These gene sets separated soft tissue sarcomas into two groups with different probabilities of developing metastatic disease. The present study used these gene sets to identify GIST subgroups with different probabilities of developing metastatic disease. METHODS: We utilized these three gene sets, hierarchical clustering, and Kaplan-Meier analysis, to examine 60 primary resected GIST samples using Agilent chip expression profiling. RESULTS: Hierarchical clustering using both the combined and individual AF-, OVCA-, and RCC- gene sets identified differences in probabilities of developing metastatic disease between the clusters defined by the first branch point of the clustering dendrograms (p = 0.029 for the combined gene set, p = 0.003 for the AF-gene set, p < 0.001 for the OVCA-gene set, and p = 0.003 for the RCC-gene set). CONCLUSIONS: Hierarchical clustering using these gene sets identified at least two subsets of GIST with distinct clinical behavior and risk of metastatic disease. The use of gene expression analysis along with other known prognostic factors may better predict the long-term outcome following surgery, and thus restrict the use of adjuvant therapy to high-risk GIST, and reduce heterogeneity among groups in clinical trials of new drugs. PMID- 26873327 TI - Early detection of unhealthy behaviors, the prevalence and receipt of antiviral treatment for disabled adult hepatitis B and C carriers. AB - BACKGROUND: Evidence indicates that hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the leading causes of liver cirrhosis and hepatocellular carcinoma. Antiviral treatments have recently been reported as successful cures. However, the prevalence rates of HBV or HCV infection, unhealthy behaviors and receipt of adequate treatment in disabled adults have not been described. The aim of this study was to examine the prevalence of HBV or HCV carriers, receipt of antiviral treatment, and early detection of unhealthy behaviors in disabled adults in Taiwan. METHODS: A population-based, cross-sectional study was conducted between July and December 2013 with 845 community-dwelling adults with disabilities aged >20 years. Statistical analyses included descriptive statistics, Chi-squared tests, and stepwise regression analysis. RESULTS: The prevalence of HBV and HCV infections was 12.9 and 14.1 %, respectively. HCV carriers tended to be older (p < 0.001) and with a lower education (p < 0.001). The majority of HBV/HCV carriers did not know the type of hepatitis infection and did not receive adequate antiviral treatment. After adjusting for potential confounding variables, regression analysis showed that the factors significantly associated with elevated liver function were HCV infection (p < 0.001), HBV infection (p = 0.001), high fasting blood glucose levels (p = 0.001), overweight (p = 0.003), older age (p = 0.027), and alcohol drinking (p = 0.028). CONCLUSIONS: There was a high prevalence of HCV infection among adults with disabilities; few received adequate antiviral treatment or early detection of unhealthy behaviors for the prevention of liver cancer. Clinicians can provide health education to help the participants and caregivers better understand the relationships between specific risk factors and liver health and can encourage HBV and HCV carriers to undergo annual physical check-ups and receive adequate treatment, as covered by the national health insurance. PMID- 26873328 TI - Clearance of bile and trypsin in rat lungs following aspiration of human gastric fluid. AB - PURPOSE: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. MATERIALS AND METHODS: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. RESULTS: In this experimental model, the half-life of bile was 9.3 hours (r(2) = 0.81), and the half-life of trypsin was 9.0 hours (r(2) = 0.68). CONCLUSIONS: The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration. PMID- 26873329 TI - RhoA/Rho-kinase activation promotes lung fibrosis in an animal model of systemic sclerosis. AB - BACKGROUND: Systemic sclerosis (SSc) is a connective-tissue disease characterized by vascular injury, immune-system disorders, and excessive fibrosis of the skin and multiple internal organs. Recent reports found that RhoA/Rho-kinase (ROCK) pathway is implicated in various fibrogenic diseases. Intradermal injection of hypochlorous acid (HOCl)-generating solution induced inflammation, autoimmune activation, and fibrosis, mimicking the cutaneous diffuse form of SSc in humans. Our study aimed firstly to describe pulmonary inflammation and fibrosis induced by HOCl in mice, and secondly to determine whether fasudil, a selective inhibitor of ROCK, could prevent lung and skin fibroses in HOCl-injected mice. METHODS: Female C57BL/6 mice received daily intradermal injection of hypochlorous acid (HOCl) for 6 weeks to induce SSc, with and without daily treatment with fasudil (30 mg.kg(-1).day(-1)) by oral gavage. RESULTS: HOCl intoxication induced significant lung inflammation (macrophages and neutrophils infiltration), and fibrosis. These modifications were prevented by fasudil treatment. Simultaneously, HOCl enhanced ROCK activity in lung and skin tissues. Inhibition of ROCK reduced skin fibrosis, expression of alpha-smooth-muscle actin and 3 nitrotyrosine, as well as the activity of ROCK in the fibrotic skin of HOCl treated mice, through inhibition of phosphorylation of Smad2/3 and ERK1/2. Fasudil significantly decreased the serum levels of anti-DNA-topoisomerase-1 antibodies in mice with HOCl-induced SSc. CONCLUSIONS: Our findings confirm HOCl induced pulmonary inflammation and fibrosis in mice, and provide further evidence for a key role of RhoA/ROCK pathway in several pathological processes of experimental SSc. Fasudil could be a promising therapeutic approach for the treatment of SSc. PMID- 26873330 TI - RNA-seq analysis reveals new candidate genes for drip loss in a Pietrain * Duroc * Landrace * Yorkshire population. AB - Drip loss, one of the most important meat quality traits, is characterized by low heritability. To date, the genetic factors affecting the drip loss trait have not been clearly elucidated. The objective of this study was to identify critical candidate genes affecting drip loss. First, we generated a Pietrain * Duroc * Landrace * Yorkshire commercial pig population and obtained phenotypic values for the drip loss trait. Furthermore, we constructed two RNA libraries from pooled samples of longissimus dorsi muscles with the highest (H group) and lowest (L group) drip loss and identified the differentially expressed genes (DEGs) between these extreme phenotypes using RNA-seq technology. In total, 25 883 genes were detected in the H and L group libraries, and none was specifically expressed in only one library. Comparative analysis of gene expression levels found that 150 genes were differentially expressed, of which 127 were upregulated and 23 were downregulated in the H group relative to the L group. In addition, 68 drip loss quantitative trait loci (QTL) overlapping with 63 DEGs were identified, and these QTL were distributed mainly on chromosomes 1, 2, 5 and 6. Interestingly, the triadin (TRDN) gene, which is involved in muscle contraction and fat deposition, and the myostatin (MSTN) gene, which has a role in muscle growth, were localized to more than two drip loss QTL, suggesting that both are critical candidate genes responsible for drip loss. PMID- 26873331 TI - Impact of Functional Versus Organic Baseline Mitral Regurgitation on Short- and Long-Term Outcomes After Transcatheter Aortic Valve Replacement. AB - The impact of the specific etiology of mitral regurgitation (MR) on outcomes in the transcatheter aortic valve replacement (TAVR) population is unknown. This study aimed to evaluate the longitudinal changes in functional versus organic MR after TAVR in addition to their impact on survival. Consecutive patients who underwent TAVR from May 2007 to May 2015 who had baseline significant (moderate or greater) MR were included. Transthoracic echocardiography was used to evaluate the cohort at baseline, post-procedure, 30-day, 6-month, and 1-year follow-up. The primary outcomes included mortality at 30 days and 1 year. Longitudinal, mixed-model regression analyses were performed to assess the differences in the magnitude of longitudinal changes of MR, left ventricular (LV) ejection fraction, and New York Heart Association functional class. Seventy patients (44% men, mean 83 years) with moderate or greater MR at baseline (30 functional vs 40 organic) were included, with the functional group having a statistically significant mean younger age and higher rates of previous coronary artery bypass grafting. Kaplan Meier cumulative mortality rates were similar: 30 days (10% vs 17.5%, unadjusted log-ranked p = 0.413) and 1 year (29.4% vs 23.2%, unadjusted log-ranked p = 0.746) in the functional versus organic MR groups, respectively. There were greater degrees of short- and long-term improvement in MR severity (slope difference p = 0.0008), LV ejection fraction (slope difference p = 0.0009), and New York Heart Association class (slope difference p = 0.0054) in the functional versus organic group. In conclusion, patients with significant functional versus organic MR who underwent TAVR have similar short- and long-term survival; nevertheless, those with a functional origin are more likely to have significant improvements in MR severity, LV-positive remodeling, and functional class. These findings may help strategize therapies for MR in patients with combined aortic and mitral valve disease who are undergoing TAVR. PMID- 26873332 TI - Conflicts of Interest and Outcomes of Cardiovascular Trials. AB - Conflicts of interests have long been recognized as potential sources of influence in the conduct and reporting of clinical trials. This controversy was again rekindled after the publication of the latest statin guidelines and a series of studies regarding competing interests in leading medical journals. We investigate the association between declared author conflicts and the outcomes of large cardiovascular trials. We searched the Medline (PubMed) database to identify "phase 2" and "phase 3" clinical trials using the search term "cardiovascular" over the past decade using "10 years" as the filter. We perceived the competing interest as present regardless of the nature such as consulting fees, honoraria, travel imbursements, stock holding, and employment. Of the 699 titles retrieved, 114 studies met the inclusion criteria. Nearly 80% of studies had at least a single author with competing interests. The 114 studies had a total of 1,433 investigators, of which 725 had declared conflicts of interests (50.6%). A total of 66 studies (58%) had half or >50 percent of investigators who had some conflicts of interests. Of these studies, 54 studies had favorable outcomes and only 12 had unfavorable outcomes (p <0.001). Among the type of competing interests, consulting or personal fees was the most common present in 58 investigators (51%). This was followed by research grants present in 55 the researchers (48%). Among 25 (22%) studies, at least one investigator reported stakes in the industry, of which only 2 studies had unfavorable outcomes for the intervention being investigated. Just 1 of the 25 clinical trials with a sample size of >1,000 had no investigators with competing interests. In conclusion, authors conflicts are associated with favorable outcomes in cardiovascular outcome trials. PMID- 26873333 TI - Assessing biocompatibility of graphene oxide-based nanocarriers: A review. AB - Graphene oxide (GO)-based nanocarriers have been frequently studied due to their high drug loading capacity. However, the unsatisfactory biocompatibility of these GO-based nanocarriers hampers their use in clinical settings. This review discusses how each of the physicochemical characteristics (e.g., size, surface area, surface properties, number of layers and particulate states) and surface coatings on GO affect its in vitro and in vivo nanotoxicity. We provide an overview on the effect of GO properties on interactions with cells such as red blood cells, macrophages and cell lines, and experimental organisms including rodents, rabbits and Zebrafish, offering some guidelines for development of safe GO-based nanocarriers. We conclude the paper by outlining the challenges involving GO-based formulations and future perspectives of this research in the biomedical field. PMID- 26873334 TI - Cellular biodistribution of polymeric nanoparticles in the immune system. AB - The biodistribution of polymeric nanoparticles (NPs) is of crucial importance in the development of nanoparticle-based vaccine delivery or immunotherapy for cancer. The purpose of this study was to investigate the kinetics of cellular biodistribution of polymeric NPs in the immune system. Polystyrene (PS) yellow green nanoparticles (YG-NPs) 500nm in diameter were intravenously (i.v.) injected into the tail veins of mice, and the kinetics of YG-NP biodistribution was followed by harvesting cells at pre-determined time points from various immune organs, including blood, bone marrow, spleen, and lymph nodes and analyzing them by polychromatic flow cytometry. To observe the location of YG-NPs in the spleen after i.v. administration, spleens of mice were isolated at 6h post-injection (p.i.), cryosectioned, immunostained, and examined by confocal microscopy. Our data show that the major phagocytosing cells included granulocytes (B220 CD11b(+)Gr-1(high)Ly-6C(low)) in the blood and bone marrow and B cells (CD11b B220(+)) in the spleen. The kinetics of the phenotypic analysis suggest the potential trans-differentiation of the B220-CD11b(+)Gr-1(low)Ly-6C(high) subset into B220-CD11b(+)Gr-1-Ly-6C- double-negative (DN) cells expressing the F4/80 macrophage phenotype in the blood and CD115 in the bone marrow after treatment with YG-NPs. Based on the microscopic analysis of spleen cryosections, the majority of YG-NPs were located in the marginal zones (MZ) and red pulp of the spleen at 6h post-injection (p.i.), allowing further interaction with MZ macrophages and granulocytes. The data obtained in this study demonstrate the kinetics of biodistribution of polymeric nanoparticles in the blood, bone marrow, and spleen at the cellular level. PMID- 26873335 TI - Analyzing spatiotemporal distribution of uniquely fluorescent nanoparticles in xenograft tumors. AB - A dose circulating through the blood at one time will have different opportunities to access the tumor compared to a dose circulating hours later. Methods to test this hypothesis allowed us to differentiate two uniquely fluorescent doses of nanoparticles (administered as a mixture or sequentially) and to measure the distribution and correlation of these nanoparticle doses in three dimensions. Multiple colocalization analyses confirm that silica nanoparticles separated into different dose administrations will not accumulate in the same location. Decreased colocalization between separate doses implies dynamic extravasation events on the scale of microns. Further, the perfusion state of different blood vessels can change across the dosing period. Lastly, analyzing the distance traveled by these silica nanoparticles in two dimensions can be an overestimation when compared with three-dimensional distance analysis. Better understanding intratumoral distribution of delivered drugs will be crucial to overcoming the various barriers to transport in solid tumors. PMID- 26873336 TI - Study of endothelial function response to exercise training in hypertensive individuals (SEFRET): study protocol for a randomized controlled trial. AB - BACKGROUND: Endothelial dysfunction is a hallmark of diabetes mellitus and systemic arterial hypertension (SAH) and an early maker for atherosclerosis. Aerobic exercise training is known to enhance endothelial function, but little is understood about the effects of resistance or combined exercise training on endothelial function. The aim of this study is to investigate the effect of a 12 week aerobic (AT), resistance (RT), or combined (aerobic and resistance, CT) training program on endothelial function and assess associated effects on blood pressure in individuals with SAH. METHODS/DESIGN: Eighty-one subjects with SAH aged 18 to 70 years will be selected and randomly assigned to three types of exercise training: AT, RT or CT. The study will involve the following procedures and tests: anamnesis, anthropometric assessment, echocardiography, blood pressure measurements through ambulatory blood pressure monitoring, flow-mediated dilation, ergospirometry, one repetition maximum test (1-RM), and blood collection (number of circulating endothelial progenitor cells, number of circulating endothelial microparticles, lipid profile, glucose, glycated hemoglobin, and creatinine). The AT intervention will consist of a 40-min exercise session with progressive intensities ranging from 50 to 75% of heart rate reserve. The RT intervention will consist of a 40-minute session with four sets of six to 12 repetitions with a rest period of 60 to 90 seconds between each set and each type of exercise. Weight loads will be adjusted to 60 to 80% of 1-RM for six types of exercise. The CT intervention will consist of a 20-min aerobic exercise session, followed by an additional 20-min resistance exercise session; each resistance exercise will have two sets less to match the total training volume. DISCUSSION: The study results are expected evidence of cardiovascular protective effects of different types of exercise training through the modulation of endothelial function in hypertensive individuals. Knowing the magnitude of improvement of endothelium-dependent vasodilation for the different types of exercise training can provide scientific evidence for the prescription of exercise programs for vascular protection targeting hypertensive individuals. TRIAL REGISTRATION: The Brazilian Clinical Trials Registry ( http://www.ensaiosclinicos.gov.br/) under RBR-9ygmdn and dated 1 March 2015. PMID- 26873337 TI - What does the multiple mini interview have to offer over the panel interview? AB - INTRODUCTION: This paper compares the panel interview (PI) performance with the multiple mini interview (MMI) performance and indication of behavioural concerns of a sample of medical school applicants. The acceptability of the MMI was also assessed. MATERIALS AND METHODS: All applicants shortlisted for a PI were invited to an MMI. Applicants attended a 30-min PI with two faculty interviewers followed by an MMI consisting of ten 8-min stations. Applicants were assessed on their performance at each MMI station by one faculty. The interviewer also indicated if they perceived the applicant to be a concern. Finally, applicants completed an acceptability questionnaire. RESULTS: From the analysis of 133 (75.1%) completed MMI scoresheets, the MMI scores correlated statistically significantly with the PI scores (r=0.438, p=0.001). Both were not statistically associated with sex, age, race, or pre-university academic ability to any significance. Applicants assessed as a concern at two or more stations performed statistically significantly less well at the MMI when compared with those who were assessed as a concern at one station or none at all. However, there was no association with PI performance. Acceptability scores were generally high, and comparison of mean scores for each of the acceptability questionnaire items did not show statistically significant differences between sex and race categories. CONCLUSIONS: Although PI and MMI performances are correlated, the MMI may have the added advantage of more objectively generating multiple impressions of the applicant's interpersonal skill, thoughtfulness, and general demeanour. Results of the present study indicated that the MMI is acceptable in a multicultural context. PMID- 26873339 TI - Heterotopic Bone in the Distal Esophagus. PMID- 26873338 TI - Case Report of a Well-Differentiated Papillary Mesothelioma of the Tunica Vaginalis in an Undescended Testis With Review of Literature. AB - Well-differentiated papillary mesothelioma (WDPM) affecting the tunica vaginalis testis is a rare tumor, and very little is known about the clinicopathological spectrum of this variant as a distinct entity. Most patients with WDPM suffer from scrotal pain or swelling, but hydrocele seems to be the most common presenting symptom. These lesions are usually not aggressive and are accompanied by an indolent clinical behavior. In this article, we report the first case known of WDPM in an undescended testis, and in addition, we review the literature for similar cases. PMID- 26873340 TI - Spitz Tumors: Comparison of Histological Features in Relationship to Immunohistochemical Staining for ALK and NTRK1. AB - Spitz tumors are a group of melanocytic neoplasms with distinct morphological features that tend to affect young individuals. Distinguishing benign from malignant Spitz tumors can be challenging, but cytogenetic and molecular tests have contributed to improvements in diagnostic accuracy. Spitz tumors harbor diverse genetic alterations, including mutations in HRAS, loss of BAP1, or kinase fusions in ROS1, NTRK1, ALK, BRAF, and RET genes. Limited data exist on the correlation between histopathological features and kinase fusions. Here, we describe the histopathological features of 105 Spitz tumors (Spitz nevi and atypical Spitz tumors), comparing lesions according to their immunoreactivity for ALK or NTRK1. Intersecting fascicular growth of fusiform melanocytes was seen in all but one ALK-positive tumor (27 of 28 or 96.4%), whereas it was infrequent in NTRK1-positive tumors (5 of 20 or 25.0%) and tumors negative for both ALK and NTRK1 (96.4% vs 25.0% vs 8.7%, P < .0027). There was a trend toward ALK-positive tumors being amelanotic compared with NTRK1-positive tumors and combined ALK /NTRK1-negative tumors (89.3% vs 45% vs 47.4%, respectively, P = .1023) and lacking epithelioid cell morphology (0% vs 45.0% vs 41%, respectively, P = .6985). In conclusion, this study confirms that although not specific, the growth pattern of intersecting fascicles of amelanotic fusiform melanocytes is strongly associated with ALK expression. PMID- 26873341 TI - Meaning of Staring and the Starer-Staree Relationship Related to Men Living With Acquired Spinal Cord Injuries. AB - When in public places, many individuals with physical disabilities experience staring. Although staring is typically seen as uncomplicated and something to be "ignored," it has consequences for the person being stared and the staree. Few studies have focused on staring experienced by men following spinal cord injury (SCI). Accordingly, this study explored how adult men with SCI give meaning to the staring from others, the consequences for them, and their responses to the staring and to the starer. Principles of modified grounded theory methods were used to conduct a secondary analysis of interview data for 30 male participants from a larger study of community-dwelling individuals with SCI. Themes revealed through analysis related to context-dependent meanings of staring, negative consequences of staring for some men, and positive opportunities for self-growth and interaction with the public. These findings contribute to a more complex understanding of staring and the relationship between the starer and staree in various social circumstances which can support people living with differences in their public interactions, and improve their quality of life. PMID- 26873342 TI - A Study of Intimate Partner Violence, Substance Abuse, and Sexual Risk Behaviors Among Gay, Bisexual, and Other Men Who Have Sex With Men in a Sample of Geosocial Networking Smartphone Application Users. AB - Geosocial-networking smartphone applications ("apps") are widely used by gay, bisexual, and other men who have sex with men (MSM) and facilitate connections between users based on proximity and attraction. MSM have sexual encounters and relationships of varying degrees of emotional and physical intimacy with app-met individuals, potentially placing them at risk for intimate partner violence (IPV). The purpose of the current study was to utilize a geosocial-networking application to investigate relationships between experiences of IPV victimization as it relates to substance use and sexual risk behaviors in a sample of MSM. Participants ( n = 175) were recruited by means of broadcast advertisements on an application widely used by MSM (Grindr) to seek sexual partners. Multivariable regression models were fit to examine associations between IPV, substance abuse, and sexual risk behaviors. Lifetime experiences of IPV victimization were common, where 37.7% of respondents reported having experienced at least one form of IPV. While a marginally significant positive association between IPV and substance abuse was detected in multivariable models ( p = .095), individual forms of IPV were strongly associated with substance abuse. For example, sexual IPV victimization was associated with an increase in substance abuse in the preceding month ( p = .004). Experiences of IPV victimization were associated with higher numbers of partners for both condomless receptive and insertive anal intercourse ( p < .05). Given the relatively high prevalence of IPV victimization and its associations with substance abuse and sexual risk behaviors, these findings suggest that IPV screening and prevention programs may reduce substance abuse and sexual risk behaviors in this population. PMID- 26873343 TI - Up-regulation of TDAG51 is a dependent factor of LPS-induced RAW264.7 macrophages proliferation and cell cycle progression. AB - CONTEXT: As a component of the outer membrane in Gram-negative bacteria, lipopolysaccharide (LPS)-induced proliferation and cell cycle progression of monocytes/macrophages. It has been suggested that the proapoptotic T-cell death associated gene 51 (TDAG51) might be associated with cell proliferation and cell cycle progression; however, its role in the interaction between LPS and macrophages remains unclear. OBJECTIVE: We attempted to elucidate the role(s) of TDAG51 played in the interaction between LPS and macrophages. MATERIALS AND METHODS: We investigated TDAG51 expression in RAW264.7 cells stimulated with LPS and examined the effects of RNA interference-mediated TDAG51 down-regulation. We used CCK-8 assay and flow cytometry analysis to evaluate the interaction between TDAG51 and LPS-induced proliferation and cell cycle progression in RAW264.7 cells. RESULTS: Our findings indicate that TDAG51 is up-regulated in LPS stimulated RAW264.7 cells, the TDAG51 siRNA effectively reduced TDAG51 protein up regulation following LPS stimulation in RAW264.7 cells, the significant changes of the proliferation and cell cycle progression of RAW264.7 cells in TDAG51 Knockdown RAW264.7 cells treated with LPS were observed. CONCLUSION: These findings suggested that TDAG51 up-regulation is a dependent event during LPS mediated proliferation and cell cycle progression, and which increase our understanding of the interaction mechanism between LPS and macrophages. PMID- 26873344 TI - K-Ras4B/calmodulin/PI3Kalpha: A promising new adenocarcinoma-specific drug target? AB - INTRODUCTION: Decades of efforts have yet to yield a safe and effective drug to target KRAS-driven pancreatic, colorectal and lung cancers; particularly those driven by the highly oncogenic splice variant KRAS4B. K-Ras4B's fairly smooth surface, cancer tissue/cell heterogeneity, tolerated lipid post-translational modification exchange, as well as drug-elicited toxicity present a daunting challenge. AREAS COVERED: Within this framework, hee we focus on a new adenocarcinoma-specific drug concept. Calmodulin (CaM) binds to K-Ras4B but not to the H-Ras or N-Ras isoforms. Physiologically, in calcium- and calmodulin-rich environments such as ductal tissues, calmodulin can sequester K-Ras4B from the membrane; in cancer, CaM/Ca(2+) can replace the missing receptor tyrosine kinase (RTK) signal, acting to fully activate PI3Kalpha. EXPERT OPINION: An oncogenic GTP-bound K-Ras4B/CaM/PI3Kalpha complex is supported by available experimental and clinical data; therefore, targeting it may address a pressing therapeutic need. High resolution electron microscopy (EM) or crystal structure of the tripartite complex would allow orthosteric or allosteric drug discovery to disrupt the CaM/PI3Kalpha interface and thus Akt/mTOR signaling. However, since drug resistance is expected to develop, combining it with compensatory pathways, particularly those involved in cell-cycle control, appears a reasonable strategy. PMID- 26873345 TI - Perspectives on Phytochemicals as Antibacterial Agents: An Outstanding Contribution to Modern Therapeutics. AB - Despite the considerable advancements in the development of antimicrobial agents, incidents of epidemics due to multi drug resistance in microorganisms have created a massive hazard to mankind. Due to increased resistance against conventional antibiotics, researchers and pharmaceutical industries are more concerned about novel therapeutic agents for the prevention of bacterial infections. Enormous wealth of traditional system of medicine gains importance in health therapies over again. With ancient credentials of potent medicinal plants, various herbal remedies came forward for the management of bacterial infections. The Ayurvedic approach facilitates the development of new therapeutic agents due to structural and functional diversity among phytochemicals. The abundance and diversity is responsible for the characterization of new lead structures from medicinal plants. Industrial interest has increased due to recent research advancements viz. synergistic and high-throughput screening approach for the evaluation of vast variety of phytochemicals. The review certainly emphasizes on the traditional medicines as alternatives to conventional chemotherapeutic drugs. The review briefly describes mode of action of various antibiotics and resistance mechanisms. This review focuses on the chemical diversity and various mechanisms of action of phytochemicals against bacterial pathogens. PMID- 26873346 TI - Illumina Spin-off to Develop Early-Detection Test. AB - DNA-sequencing giant Illumina has formed a new company, called Grail, to develop liquid biopsies capable of spotting cancer before symptoms arise. The start-up is working on a low-cost "pan-cancer" test that can detect multiple cancer types early, which it hopes to introduce by 2019. PMID- 26873347 TI - STAT5 Is a Key Regulator in NK Cells and Acts as a Molecular Switch from Tumor Surveillance to Tumor Promotion. AB - Natural killer (NK) cells are tightly regulated by the JAK-STAT signaling pathway and cannot survive in the absence of STAT5. We now report that STAT5-deficient NK cells can be rescued by overexpression of BCL2. Our experiments define STAT5 as a master regulator of NK-cell proliferation and lytic functions. Although NK cells are generally responsible for killing tumor cells, the rescued STAT5-deficient NK cells promote tumor formation by producing enhanced levels of the angiogenic factor VEGFA. The importance of VEGFA produced by NK cells was verified by experiments with a conditional knockout of VEGFA in NK cells. We show that STAT5 normally represses the transcription of VEGFA in NK cells, in both mice and humans. These findings reveal that STAT5-directed therapies may have negative effects: In addition to impairing NK-cell-mediated tumor surveillance, they may even promote tumor growth by enhancing angiogenesis. SIGNIFICANCE: The importance of the immune system in effective cancer treatment is widely recognized. We show that the new signal interceptors targeting the JAK-STAT5 pathway may have dangerous side effects that must be taken into account in clinical trials: inhibiting JAK-STAT5 has the potential to promote tumor growth by enhancing NK cell-mediated angiogenesis. PMID- 26873348 TI - Shifts of attention bias awareness of voluntary and reflexive eye movements. AB - Current theories regarding factors that influence people's awareness of their actions have underscored the role of peripheral signals (e.g., proprioceptive feedback) and central commands (e.g., the intention to make a response). The role of covert attention has been largely underexplored, even though attention and awareness have been tightly linked. The aim of the current study was to directly examine the impact of shifts of visual attention on people's awareness of their eye movements as they performed the antisaccade task. People tend to be unaware of a high percentage of erroneous eye movements on this task, thus lending it to the study of variables that might modulate people's awareness of their actions. In addition, this task provides the opportunity to compare two classes of actions, voluntary (antisaccade) and involuntary (erroneous prosaccade) eye movements, and thus to assess whether shifts of covert attention can or cannot override sources of information that may be present when people make voluntary but not reflexive responses. We found that shifts of visual attention did indeed influence participants' awareness of their own eye movements, leading them to misperceive reflexive and voluntary movements alike, suggesting that covert attention may override both peripheral and central signals to bias awareness. PMID- 26873349 TI - Exploring the interaction of physical exercise load and pattern recall performance in female handball players. AB - Studies examining experts' superiority within domain-specific structured pattern recall tasks have typically had athletes perform them at rest, which is far different from how they are executed in their sport. The aim of this study was to investigate whether performing these tasks under different physical exercise intensities influenced pattern recall results of experts, advanced and novices. In two experiments, 68 participants (experiment 1: n = 33; experiment 2: n = 35) were tested using a handball-specific pattern recall task both at rest and during physical exercise. Physical exercises of 60 % heart rate reserve (constant workload: experiment 1) and of 86.5-90 % HRmax (handball-specific interval load: experiment 2) were induced. Results of both experiments revealed significant group differences with experts recalling patterns more accurately than novices but no significant within-subject differences for the two conditions and no interaction between both factors. Our findings replicate prior research concerning perceptual-cognitive expertise in structured specific pattern recall tasks. However, the lack of intergroup differences between the two conditions or interactions was surprising, suggesting sport-specific pattern recall skill is robust to changes in exercise stimuli. Future work is needed to further examine the impact of "physiological specificity" on perceptual-cognitive expertise. PMID- 26873352 TI - ECR 2016 Book of Abstracts - C - Scientific and Educational Exhibits. PMID- 26873350 TI - Exposing sequence learning in a double-step task. AB - Is it possible to learn to perform a motor sequence without awareness of the sequence? In two experiments, we presented participants with the most elementary sequence: an alternation between two options. We used a double-step pointing task in which the final position of the target alternated between two quite similar values. The task forced participants to start moving before the final target was visible, allowing us to determine participants' expectations about the final target position without explicitly asking them. We tracked participants' expectations (and thus motor sequence learning) by measuring the direction of the initial part of the movement, before any response to the final step. We found that participants learnt to anticipate the average size of the final step, but that they did not learn the sequence. In a second experiment, we extended the duration of the learning period and increased the difference in size between the target position changes. Some participants started anticipating the step size in accordance with the sequence at some time during the experiment. These participants reported having noticed the simple sequence. The participants who had not noticed the sequence did not move in anticipation of the sequence. This suggests that participants who did not learn this very simple sequence explicitly also did not learn it implicitly. PMID- 26873351 TI - Body fat measurement in adolescent girls with type 1 diabetes: a comparison of skinfold equations against dual-energy X-ray absorptiometry. AB - AIM: Skinfold measurement is an inexpensive and widely used technique for assessing the percentage of body fat (%BF). This study assessed the accuracy of prediction equations for %BF based on skinfold measurements compared to dual energy X-ray absorptiometry (DXA) in girls with type 1 diabetes and healthy age matched controls. METHODS: We included 49 healthy girls and 44 girls with diabetes aged 12-19 years old, comparing the predicted %BF based on skinfold measurements and the %BF values obtained by a Lunar DPX-L scanner. The agreement between the methods was assessed using an Bland-Altman plot. RESULTS: The skinfold measurements were significantly higher in girls with diabetes (p = 0.003) despite a nonsignificant difference in total %BF (p = 0.1). A significant association between bias and %BF was found for all tested equations in the Bland Altman plots. Regression analysis showed that the association between skinfold measurements and %BF measured by DXA differed significantly (p = 0.039) between the girls with diabetes and the healthy controls. CONCLUSION: The accuracy of skinfold thickness equations for assessment of %BF in adolescent girls with diabetes is poor in comparison with DXA measurements as criterion. Our findings highlight the need for the development of new prediction equations for girls with type 1 diabetes. PMID- 26873353 TI - ECR 2016 Book of Abstracts - A - Postgraduate Educational Programme. PMID- 26873354 TI - ECR 2016 Book of Abstracts - D - Satellite Symposia. PMID- 26873356 TI - ECR 2016 Book of Abstracts - F - List of Authors & Co-Authors. PMID- 26873357 TI - ECR 2016 Book of Abstracts - G - List of Moderators. PMID- 26873358 TI - ECR 2016 Book of Abstracts - B - Scientific Sessions and Clinical Trials in Radiology. PMID- 26873359 TI - Incidence of numerical variants and transitional lumbosacral vertebrae on whole spine MRI. AB - OBJECTIVES: This study sets out to prospectively investigate the incidence of transitional vertebrae and numerical variants of the spine. MATERIALS AND METHODS: Over a period of 28 months, MRIs of the whole spine were prospectively evaluated for the presence of transitional lumbosacral vertebrae and numerical variants of the spine. RESULTS: MRI of the whole spine was evaluated in 420 patients, comprising 211 female and 209 male subjects. Two patients had more complex anomalies. Lumbosacral transitional vertebrae were seen in 12 patients: eight sacralised L5 (3 male, 5 female) and four lumbarised S1 (3 male, 1 female). The incidence of transitional vertebrae was approximately 3.3. % (14/418). Thirty two (7.7 %) of 418 patients had numerical variants of mobile vertebrae of the spine without transitional vertebrae. The number of mobile vertebrae was increased by one in 18 patients (12 male, 6 female), and the number was decreased by one in 14 patients (4 male, 10 female). CONCLUSIONS: Numerical variants of the spine are common, and were found to be almost 2.5 times as frequent as transitional lumbosacral vertebrae in the study population. Only whole-spine imaging can identify numerical variants and the anatomical nature of transitional vertebrae. The tendency is toward an increased number of mobile vertebrae in men and a decreased number in women. Main messages * Numerical variants of the spine are more common than transitional vertebrae. * Spinal numerical variants can be reliably identified only with whole-spine imaging. * Increased numbers of vertebrae are more common in men than women. * Transitional lumbosacral vertebrae occurred in about 3.3 % of the study population. * The incidence of numerical variants of the spine was about 7.7 %. PMID- 26873360 TI - Assessing understandings of substance use disorders among Norwegian treatment professionals, patients and the general public. AB - BACKGROUND: Beliefs about substance use disorder (SUD) shape how patients, treatment professionals and the general public view addiction and its treatment. A U.S. developed scale exists to assess such beliefs, but it has never been tested in Norway nor normed on any general population sample. METHODS: The Short Understanding of Substance Abuse Scale (SUSS) was translated from English to Norwegian and used to assess beliefs about the nature of addiction among addiction treatment professionals (N = 291), patients with SUDs (N = 133) and respondents from the general public (N = 216). The disease and psychosocial model subscales of the SUSS were examined with a multigroup factor analysis to confirm that the constructs were invariant across the studied groups. We also controlled for demographic covariates in a multiple indicator multiple cause model. RESULTS: The multigroup confirmatory factor analysis of the SUSS yielded a partial scalar invariant model and thus, we were able to compare latent means between groups. In unadjusted comparisons, patients and the general public reported significantly higher endorsement of disease model beliefs than did professionals. However, the difference between professionals and the general public disappeared when the comparison was adjusted for covariates (i.e., age, gender, education). In both unadjusted and adjusted analyses, the general public group but not the patient group scored significantly lower than professionals on the psychosocial belief scale. CONCLUSION: The SUSS is useable with slight adaptations in Norwegian samples. Norwegian treatment professionals have different views of substance use disorder than do patients and the general public. This may create opportunities for dialogue and mutual learning, but also presents risk of miscommunication and distrust. PMID- 26873361 TI - How do patients and doctors-to-be perceive systemic lupus erythematosus? AB - The aim of the present study was to assess and compare illness perception of systemic lupus erythematosus (SLE) held by 6th-year medical students and patients suffering from SLE. The study group consisted of 104 students (66 women; 63.5 %), mean age 24.7 (+/-1), and 64 outpatients with SLE (60 women; 93.7 %). All patients were treated at a university rheumatology outpatient clinic. Mean patients' age was 44.3 years (+/-12.5). Mean duration of the disease was 11 years (+/-6.8). The Polish version of Brief Illness Perception Questionnaire (B-IPQ) was used to assess five dimensions of illness perception. The students were asked to complete a modified version of B-IPQ designed to measure health professionals' illness perception. Significant differences were found in all but one B-IPQ scores. The students obtained significantly higher scores than the SLE patients in consequences, identity, concern and emotional response, whereas significantly lower scores in personal control, treatment control and understanding were noted among students. No differences were found in timeline scores. Medical students' perception of SLE is more threatening and more negative than that of patients'. Doctors-to-be perceive SLE as being less controllable, more burdensome and having more consequences than patients do. Additionally, they believe the disease causes more emotional concern. The article discusses possible explanations together with positive and negative aspects of the discrepancies. PMID- 26873363 TI - India sets out plan to eliminate malaria by 2030. PMID- 26873362 TI - Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene Environment Interactions in a Uyghur Population. AB - BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY(r)SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. RESULTS Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661 rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). CONCLUSIONS Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population. PMID- 26873364 TI - MRI-guided liposomes for targeted tandem chemotherapy and therapeutic response prediction. AB - Liposomes are effective drug delivery systems that can be functionalized with imaging contrast agents, providing both diagnosis and monitoring of disease treatment. Here we describe the design of a theranostic liposomal drug delivery system whose biodistribution can be real time imaged by contrast enhanced MRI and can achieve tandem chemotherapy drug delivery. Because T1 relaxation of MRI depends upon the chemical structure of contrast agent as well as its interaction with neighbor environment, we rationally designed a functional liposome for in vivo T1 enhanced MRI. The liposome shows a 36-fold higher T1 relaxation rate over the commercial MRI contrast agent Omniscan(r) and a long circulation time up to 300min in vivo. Moreover, the multifunctional liposome carries both hydrophobic and hydrophilic chemotherapeutic drugs, can synergistically enhance therapeutic effects of multiple drugs and selectively deliver them to lung tumors, leading to lower doses, toxicity and sustained release. The nanoparticles, which exhibit favorable biodistributions to tumors, offer new possibilities for the simultaneous delivery of more than one drug and the evaluation of therapeutic response in vivo by T1 enhanced MRI. STATEMENT OF SIGNIFICANCE: Cancer cells invoke different mechanisms to resist cancer therapies, particularly when delivering a single agent in a given therapy. The combination of two (or more) thermotherapy agents provides a promising way to circumvent such situations of drug resistance, due to a favorable synergistic effect that "tricks" the drug resistance mechanism. However, challenges to the simultaneous delivery of two drugs prevail, especially with regards to the simultaneous delivery of hydrophobic and hydrophobic drugs. Furthermore, non-invasive in vivo imaging of drug distribution enables the real-time monitoring and prediction of therapeutic responses to treatment. In this study, we rationally designed a theranostic liposomal drug delivery system whose biodistribution can be imaged via T1 weighted MRI in real-time and can achieve tandem chemotherapy drug delivery. This original study will be of considerable use to the wider drug delivery community. PMID- 26873366 TI - Constructing aptamer anchored nanovesicles for enhanced tumor penetration and cellular uptake of water soluble chemotherapeutics. AB - Polymersomes represent a promising pharmaceutical vehicle for the delivery of hydrophilic therapeutic agents. However, modification of polymersomes with molecules that confer targeting functions remains challenging because of the strict requirements regarding the weight fractions of the hydrophilic and hydrophobic block polymers. In this study, based on the compatibility between cholesterol and polymeric carriers, polymersomes self-assembled by amphiphilic graft polyphosphazenes were endowed with a targeting function by incorporating the cholesterol-linked aptamer through a simple dialysis method. The aqueous interior of the polymersomes was employed to encapsulate water-soluble doxorubicin hydrochloride. In vivo experiments in tumor-bearing mice showed that the aptamer-anchored vesicle targeted accumulation at the tumor site, favorable penetration through tumor tissue, and incremental endocytosis into tumor cells. Correspondingly, the aptamer-anchored vesicle decreased systemic toxicity and effectively suppressed the growth of subcutaneous MCF-7 xenografts. These findings suggested that vesicles modified with targeted groups via hydrophobic supermolecular interactions could provide a platform for selective delivery of hydrophilic drug. STATEMENT OF SIGNIFICANCE: Polymersomes have represented a promising type of pharmaceutical vehicles due to their predominant physical properties. However, it is still a challenge to endow polymersomes with active target function because of strict requirements of the weight fractions of hydrophilic polymer block to hydrophobic one. In this research, by taking advantage of the supermolecular interactions between amphiphilic graft polyphosphazene and cholesterol which was linked to aptamer AS1411, we prepared a targeted functional polymersome (PEP-DOX.HCl-Ap) through a simple method with high loading of water soluble anti-cancer drug doxorubicin hydrochloride. The in vivo experiments in MCF-7 tumor-bearing mice demonstrated several advantages of PEP-DOX.HCl-Ap vesicle such as prolonged circulation time in blood, targeted accumulation at tumor site, permeation through the tumor tissue and incremental endocytosis by tumor cells, which consequently resulted in the significantly improved anti-cancer efficacy. Moreover, this novel polymersome designed in this study has built a research platform to achieve targeted delivery of hydrophilic chemotherapeutics for cancer therapy. PMID- 26873367 TI - Matrices secreted during simultaneous osteogenesis and adipogenesis of mesenchymal stem cells affect stem cells differentiation. AB - The extracellular matrix (ECM) plays a pivotal role in regulating stem cell functions. The ECM dynamically changes during tissue development. It remains a great challenge to mimic the dynamically changing ECM. In this study, we prepared novel types of extracellular matrices that could mimic the dynamic variation of extracellular matrices, which were derived from simultaneous osteogenesis and adipogenesis of human bone marrow-derived mesenchymal stem cells (MSCs). Four ECMs simultaneously mimicking early osteogenesis and early adipogenesis (EOEA), early osteogenesis and late adipogenesis (EOLA), late osteogenesis and early adipogenesis (LOEA), late osteogenesis and late adipogenesis (LOLA) were prepared. The stepwise osteogenesis-co-adipogenesis-mimicking matrices had different compositions and different effects on the osteogenic and adipogenic differentiation of MSCs. The matrices could provide very useful tools to investigate the interaction between ECM and stem cells and the role of ECM on stem cell differentiation. STATEMENT OF SIGNIFICANCE: Extracellular matrices (ECMs) are dynamically remodeled to regulate stem cell functions during tissue development. Until now, mimicking the ECM variation during stem cell differentiation to single cell type has been reported. However, there is no report on simultaneous mimicking of stem cell differentiation to two types of cells. In this study, we prepared the mixture ECMs derived from simultaneous osteogenesis and adipogenesis of MSCs at different stages and found that they could regulate stem cell differentiation. The concept is new and the ECMs are novel. No such ECMs have been reported previously. The matrices will provide very useful tools to investigate the interaction between ECM and stem cells and the role of ECM on stem cell differentiation. PMID- 26873368 TI - Engineered zwitterionic phosphorylcholine monolayers for elucidating multivalent binding kinetics of C-reactive protein. AB - Understanding of the activation dynamics of C-reactive protein (CRP) on plasma membranes is important in the development of zwitterionic biomaterials for their uses in the tissues of inflammation and infection. Previously, the use of a zwitterionic phosphorylcholine group, a biomimetic ligand for CRP in the presence of calcium ions, for binding experiments has revealed that the adsorption dynamics changed by ionic microenvironments. Here we focused on the effect of the ligand density on a surface, a major physicochemical parameter, on the multivalent binding modes. A building block from synthetic origin, a phospholipid analogue with thiol ends, was developed for making a cell membrane-mimicked self assembled monolayers with tunable lateral ligand density on the molecular basis. The multivalent binding kinetics of CRP, a pentraxin in the original conformation, onto the engineered surface was measured using a surface plasmon resonance technique. The binding experiments revealed that the on-rate and off rate constants in the first ligand-occupation reaction increased with increasing the ligand density, which resulted in stable values of the dissociation constant. Notably, the binding affinity in the second ligand-occupation reaction showed the optimal value as a function of the ligand density. Moreover, the binding experiments using a monomeric CRP-specific DNA aptamer revealed that pentameric CRP underwent structural transition into the monomers following the adsorption onto the surfaces via multivalent contacts in a pH-dependent manner. The bioengineering-based approach reveals for the first time how the multiple binding reaction is altered by the ligand arrangement at the molecular resolution and how CRP is activated by the conformational transition induced by the multiplex bindings. STATEMENT OF SIGNIFICANCE: C-reactive protein (CRP), a major acute phase pentraxin, binds to plasma membranes through the multivalent contacts with zwitterionic phosphorylcholine groups. However, details in the molecular dynamics is unknown due to a lack of proper sensing platform. The paper describe the synthesis of thiol-functionalized phosphorylcholine for the development of a robust cell membrane-mimetic surface on a surface plasmon resonance sensor at desired lateral ligand densities. The engineered approach on molecular basis enables a rigorous arrangement of the ligand on the surface, whose tunability and robustness are not achieved using conventional supported lipid layers. The effect of the ligand density on the multivalent binding kinetics provides the understanding of how the multivalent contacts induce conformational transitions of CRP and responses to inflammation. PMID- 26873365 TI - Cationic, amphiphilic copolymer micelles as nucleic acid carriers for enhanced transfection in rat spinal cord. AB - Spinal cord injury commonly leads to permanent motor and sensory deficits due to the limited regenerative capacity of the adult central nervous system (CNS). Nucleic acid-based therapy is a promising strategy to deliver bioactive molecules capable of promoting axonal regeneration. Branched polyethylenimine (bPEI: 25kDa) is one of the most widely studied nonviral vectors, but its clinical application has been limited due to its cytotoxicity and low transfection efficiency in the presence of serum proteins. In this study, we synthesized cationic amphiphilic copolymers, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP), by grafting low molecular weight PLGA (4kDa) to bPEI (25kDa) at approximately a 3:1 ratio as an efficient nonviral vector. We show that PgP micelle is capable of efficiently transfecting plasmid DNA (pDNA) and siRNA in the presence of 10% serum in neuroglioma (C6) cells, neuroblastoma (B35) cells, and primary E8 chick forebrain neurons (CFN) with pDNA transfection efficiencies of 58.8%, 75.1%, and 8.1%, respectively. We also show that PgP provides high-level transgene expression in the rat spinal cord in vivo that is substantially greater than that attained with bPEI. The combination of improved transfection and reduced cytotoxicity in vitro in the presence of serum and in vivo transfection of neural cells relative to conventional bPEI suggests that PgP may be a promising nonviral vector for therapeutic nucleic acid delivery for neural regeneration. STATEMENT OF SIGNIFICANCE: Gene therapy is a promising strategy to overcome barriers to axonal regeneration in the injured central nervous system. Branched polyethylenimine (bPEI: 25kDa) is one of the most widely studied nonviral vectors, but its clinical application has been limited due to cytotoxicity and low transfection efficiency in the presence of serum proteins. Here, we report cationic amphiphilic copolymers, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) that are capable of efficiently transfecting reporter genes and siRNA both in the presence of 10% serum in vitro and in the rat spinal cord in vivo. The combination of improved transfection and reduced cytotoxicity in the presence of serum as well as transfection of neural cells in vivo suggests PgP may be a promising nucleic acid carrier for CNS gene delivery. PMID- 26873370 TI - Meta-analysis of prognostic studies for a biomarker with a study-specific cutoff value. AB - In prognostic studies, a summary statistic such as a hazard ratio is often reported between low-expression and high-expression groups of a biomarker with a study-specific cutoff value. Recently, several meta-analyses of prognostic studies have been reported, but these studies simply combined hazard ratios provided by the individual studies, overlooking the fact that the cutoff values are study-specific. We propose a method to summarize hazard ratios with study specific cutoff values by estimating the hazard ratio for a 1-unit change of the biomarker in the underlying individual-level model. To this end, we introduce a model for a relationship between a reported log-hazard ratio for a 1-unit expected difference in the mean biomarker value between the low-expression and high-expression groups, which approximates the individual-level model, and propose to make an inference of the model by using the method for trend estimation based on grouped exposure data. Our combined estimator provides a valid interpretation if the biomarker distribution is correctly specified. We applied our proposed method to a dataset that examined the association between the biomarker Ki-67 and disease-free survival in breast cancer patients. We conducted simulation studies to examine the performance of our method. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26873369 TI - Dipeptidyl Peptidase (DPP)-4 Inhibitor-Induced Arthritis/Arthralgia: A Review of Clinical Cases. AB - Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral drugs used for the treatment of type 2 diabetes mellitus (T2DM). The pharmacological inhibition of DPP-4 seems to also induce adverse events related to cytokine-induced inflammation. Recently, several clinical cases regarding the association of DPP-4 inhibitors and the onset of arthritis/arthralgia have been reported in the literature. Various mechanisms could be responsible for DPP-4 inhibitor-induced arthritis/arthralgia, and the increase of cytokines, chemokines, matrix metalloproteinases (MMPs) and genetic factors plays an important role. The US FDA published a safety announcement regarding the entire drug class, encouraging healthcare professionals and patients to pay attention to the occurrence of arthralgia during treatment with DPP-4 inhibitors; arthralgia could be assessed as a class adverse drug event for DPP-4 inhibitors. To summarize the evidence on the correlation between DPP-4 inhibitors and arthritis/arthralgia, and to explain the measures taken by the FDA with regard to arthralgia risk, we performed a literature review of recent evidence concerning this association. This review shows the necessity of other studies to better define the association between DPP 4 inhibitors and arthritis/arthralgia. PMID- 26873371 TI - A Study of Chief Nurse Executives Indicates Low Prioritization of Evidence-Based Practice and Shortcomings in Hospital Performance Metrics Across the United States. AB - BACKGROUND: Although findings from studies indicate that evidence-based practice (EBP) results in high-quality care, improved patient outcomes, and lower costs, it is not consistently implemented by healthcare systems across the United States and globe. AIMS: The purpose of this study was to describe: (a) the EBP beliefs and level of EBP implementation by chief nurse executives (CNEs), (b) CNEs' perception of their hospitals' EBP organizational culture, (c) CNEs' top priorities, (d) amount of budget invested in EBP, and (e) hospital performance metrics. METHODS: A descriptive survey was conducted. Two-hundred-seventy-six CNEs across the United States participated in the survey. Valid and reliable measures included the EBP Beliefs scale, the EBP Implementation scale, and the Organizational Culture and Readiness scale for EBP. The Centers for Medicare and Medicaid Services Core Measures and the National Database of Nursing Quality Indicators (NDNQI) were also collected. RESULTS: Data from this survey revealed that implementation of EBP in the practices of CNEs and their hospitals is relatively low. More than one-third of the hospitals are not meeting NDNQI performance metrics and almost one-third of the hospitals are above national core measures benchmarks, such as falls and pressure ulcers. LINKING EVIDENCE TO ACTION: Although CNEs believe that EBP results in high-quality care, it is ranked as a low priority with little budget allocation. These findings provide a plausible explanation for shortcomings in key hospital performance metrics. To achieve higher healthcare quality and safety along with decreased costs, CNEs and hospital administrators need to invest in providing resources and an evidence based culture so that clinicians can routinely implement EBP as the foundation of care. PMID- 26873372 TI - The Strengths and Challenges of Implementing EBP in Healthcare Systems. AB - BACKGROUND: Multihospital healthcare system leaders and individual nurses are challenged to integrate standardized evidence-based practices that support continuous performance improvement in their systems. AIM: This study was undertaken to evaluate the strength of and the opportunities for implementing evidence-based nursing practice across a diverse 9-hospital system located in the mid-Atlantic region. METHODS: A cross-sectional survey of 6,800 registered nurses (RNs), with a 24% response rate, was conducted to learn about their attitudes, beliefs, and perceptions toward organizational readiness and implementation of EBP. RESULTS: Although respondents' beliefs about EBP were positive, they reported their ability to implement EBP as extremely low. More than one third (36%) of the respondents worked at two of the system's Magnet designated hospitals. Magnet RNs reported more resources and held more positive beliefs about their hospital's organizational readiness for EBP. Nurses who possess advanced nursing degrees, certification, and who serve in leadership roles were favorable toward EBP. Younger RNs with fewer years in practice were more likely to have positive beliefs toward EBP and embedding it into the organizational culture. LINKING EVIDENCE TO PRACTICE: Findings mirror previous research where nurses internationally favor EBP yet struggle with similar barriers for implementation. Strategies to link this evidence to action can be taken at local and global levels. Locally, transformational nurse leaders within each hospital can share the vision for implementing EBP and embrace Magnet principles. At the system level, transformational nurse leaders can collectively allocate resources to create a system-wide online EBP education plan with EBP competencies and tool kit to increase RN exposure to EBP and standardize practice. Globally, promoting free and accessible EBP massive open online courses (MOOC) and sharing best practices online and at international forums such as Magnet conferences will help to lead, educate, and mentor nurses with strategies to systematically increase EBP uptake. PMID- 26873373 TI - Treatment Fidelity of an Evidence-Based Nurse-Led Intervention in a Proactive Primary Care Program for Older People. AB - BACKGROUND: In a large randomized trial, Utrecht PROactive Frailty Intervention Trial (U-PROFIT), we evaluated the effectiveness of an integrated program on the preservation of daily functioning in older people in primary care that consisted of a frailty identification tool and a multicomponent nurse-led care program. Examination of treatment fidelity is critical to successful translation of evidence-based interventions into practice. AIMS: To assess treatment delivery, dose and content of nursing care delivered within the nurse-led care program, and to explore if the delivery may have influenced the trial results. METHODS: A mixed-methods study was conducted. Type and dose of nursing care were collected during the trial. Shortly after the trial, a focus group with nurses was conducted to explore reasons for the observed differences between the type and dose of nursing care delivered. RESULTS: A total of 835 older persons were included in the nurse-led care program. The mean age was 75 years, 64% were female and 53.5% were living alone. The most frequent self-reported conditions were loneliness (60.8%) and cognitive problems (59.4%). One-third of the patients with a geriatric condition received an additional assessment (e.g., Mini-Mental State Examination), and the majority of these patients received at least one nurse intervention (>85%). Most nursing care was delivered to patients at risk of falling and to those with urinary incontinence. Patients with nutrition problems seldom received nursing interventions. The nurses explained that differences in type and dose were influenced by the preference of the patient, the type of geriatric problem, and the time required to apply a nurse intervention. LINKING EVIDENCE TO ACTION: All intervention components were delivered; however, differences were observed in the type and dose of nursing care delivered across geriatric conditions. The findings better explain the treatment fidelity and suggest that there is room for improvement that may result in more beneficial patient outcomes. PMID- 26873374 TI - Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing. AB - Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured rho(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds. PMID- 26873375 TI - Virulence factors of Streptococcus pyogenes strains from women in peri-labor with invasive infections. AB - Invasive group A streptococcal (GAS) infections constitute an important epidemiological problem. Many cases occur in women during the postnatal period. The objective of this study was to evaluate the presence of the genes responsible for production of iron-chelating protein (perR) and superantigens (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, and ssa) in S. pyogenes strains isolated from invasive infections in women after delivery. Furthermore, this study sought to verify whether S. pyogenes strains show special phenotypic and genotypic (sla, spy1325) characteristics that may play a decisive role in adherence to the genital tract epithelium. Moreover, the emm-types and antibiotic susceptibility were determined. We tested 30 invasive S. pyogenes strains isolated from postpartum invasive infection and 37 GAS control strains isolated from the genital tracts of asymptomatic multiparous women. The majority of the tested strains were shown to express two types of emm genes (1 and 28), though emm -12, -28, -75 and -89 were uniquely expressed in the group of strains isolated from invasive infections. A significantly higher prevalence of perR in the strains from puerperal fever was shown. Significant differences were also found between the two groups with respect to the incidence of the genes related to adherence; GAS strains originating from women with sepsis/puerperal fever showed presence of these genes less frequently than those of the control group. Although differences in frequencies of the gene coding for various superantigens were noted between the compared groups of GAS strains, they were not significant. PMID- 26873377 TI - Genotype-specific concordance of oral and genital human papillomavirus infections among marital couples is low. AB - Data on genotype-specific concordance of oral-oral and genital-oral HPV infections among marital couples are key to understand HPV transmission between spouses. Genotype-specific concordance of HPV infections (oral/genital) and their co-variates among 131 marital couples were determined during 6-year follow-up (FU). Seven oral scrapings were taken from both spouses, accompanied by six genital samplings from the women and one (at baseline) from the male partners. HPV-genotyping was performed by nested PCR and a Luminex(r)-based Multimetrix Assay. Demographic data were collected with questionnaires at baseline and study conclusion. Prevalence of oral HPV varied from 10.3 to 27.0 % and 15.8 to 31.3 % in women and men, respectively. At baseline, 37.6 % of the male genital samples were HPV-positive while in female genital samples, HPV prevalence varied from 13.3 to 59.4 %. Only 15 couples had HPV genotype-specific concordance (oral-oral n = 7; male oral-female genital n = 9; female oral-male genital n = 2). In the nested case-control setting, higher number of deliveries (OR 0.145, 95%CI 0.030 0.706, p = 0.017) and higher number of intercourse (OR 0.488, 95%CI 0.243-0.978, p = 0.043) decreased the likelihood of concordant HPV infections while practicing oral sex increased the risk (OR 0.299, 95%CI 0.120-0.748, p = 0.010). In multivariate analysis, the likelihood of concordance was decreased by higher number of pregnancies of the female partner (p = 0.020) and by higher frequency of intercourse reported by the male spouse (p = 0.027). To conclude, asymptomatic HPV infections were common in both spouses while genotype-specific concordance was low. This supports the view that HPV profile of the spouses has been established before the current marital relationship. PMID- 26873376 TI - Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection. AB - Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments. PMID- 26873378 TI - Predictors of ertapenem therapeutic efficacy in the treatment of urinary tract infections (UTIs) in hospitalized adults: the importance of renal insufficiency and urinary pH. AB - In hospitalized adults acute uncomplicated cystitis (AUC) and catheter associated bacteriuria (CAB) may be treated with oral antibiotics. With AUC or CAB due to extended spectrum beta-lactamase (ESBL) + Gram negative bacilli (GNB) physicians often use intravenous therapy, e.g., ertapenem. We reviewed our recent experience in hospitalized adults with AUC and CAB treated with ertapenem. Therapeutic efficacy of ertapenem was assessed by decreased pyuria/bacteriuria, and elimination of the uropathogen. The effectiveness of ertapenem in the presence of renal insufficiency (CrCl < 50 ml/min) and acid and alkaline urinary pH were evaluated. In addition, rapidity of eradication of bacteriuria was assessed by time to negative urine cultures (TTNC). In those with an acid urinary pH ertapenem was highly effective in eliminating bacteriuria (TTNC < 3 days). TTNC was prolonged ( >3 days) in patients with decreased renal function and alkaline urinary pH. We reviewed 45 hospitalized adults with AUC or CAB to determine if renal insufficiency and or alkaline urinary pH affected ertapenem efficacy. In the 33 adult hospitalized patients with AUC and 12 with CAB, we found that ertapenem was consistently effective in eliminating the GNB bacteriuria. In hospitalized adults, the presence of renal insufficiency and acid urine, bacteriuria was eliminated in < 3 days. However, in those with renal insufficiency and an alkaline urine pH, the rapidity of cure, i.e., time to negative cultures (TTNC) was prolonged, i.e., > 3 days which has not been previously reported. PMID- 26873379 TI - Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment. AB - Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged <=64 years (OR = 0.969, p < 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged >64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes. PMID- 26873380 TI - Population-based epidemiology of Staphylococcus aureus bloodstream infection: clonal complex 30 genotype is associated with mortality. AB - Staphylococcus aureus bloodstream infections (SABSI) are associated with a high burden of morbidity and mortality. The impact of specific S. aureus genotypes on outcome is unclear. The aim of this study was to evaluate the epidemiology and outcome of SABSI, with a special emphasis on the impact of bacterial clonal lineage on mortality. We conducted a 3-year population-based prospective study between 2011 and 2014, including 303 consecutive adult patients. Clinical data were obtained from interviews and medical records. S. aureus isolates were genotyped using DNA microarrays. The incidence rate of SABSI was 27.6 per 100,000 inhabitants [95 % confidence interval (CI) 24.6-31.0]. The median age of the patients was 71 years (interquartile range 56-81 years) and 61.4 % were male. Most SABSI (70.6 %) occurred in hospitals or associated to healthcare, and 34.1 % of these were associated with intravascular catheters. Only five (1.6 %) SABSI were caused by methicillin-resistant S. aureus (MRSA). The 30-day case fatality rate was 20.8 % (95 % CI 16.6-25.7). S. aureus clonal complex 30 [hazard ratio (HR) 3.9; 95 % CI 1.8-8.5, p = 0.001], unknown focus of infection (HR 4.5; 95 % CI 1.9-10.8, p = 0.001) and respiratory tract infection (HR 12.7; 95 % CI 4.6 34.6, p < 0.001) were independent predictors of mortality in a Cox regression analysis after adjusting for age, sex and underlying conditions. A high proportion of potential preventable SABSI calls for effective infection control measures. S. aureus clonal complex 30 genotype was associated with mortality in patients with bloodstream infections. The genetic basis underlying this association remains to be demonstrated. PMID- 26873381 TI - Risk factors for long-term mortality of Staphylococcus aureus bacteremia. AB - Staphylococcus aureus bacteremia (SAB) is a fatal disease. We aimed to describe risk factors for long-term mortality with SAB. We analyzed data from a retrospectively collected database including 1,692 patients with SAB. We considered variables of infection and background conditions for the analysis of long-term survival. The Kaplan-Meier procedure was used for analysis of long-term survival. Variables significantly associated with mortality were analyzed using a Cox regression model. We included 1,692 patients in the analysis. Patients were followed for up to 22 years. Within one year, 62% of patients died and within 5 years 72% died. A total of 82% of patients aged 65 years and older died within 5 years. Independent predictors of long-term mortality were older age (Hazard ratio 1.029, 95% confidence interval 1.022-1.036), female gender (HR 1.302, 95% CI 1.118-1.517), pneumonia or primary/ unknown source of infection (HR 1.441, 95% CI 1.230-1.689), dementia (HR 1.234, 95% CI 1.004-1.516), higher Charlson score (HR 1.155, 95% CI 1.115-1.196), shock at onset (HR 1.776, 95% CI 1.430-2.207) and arrival to hospitalization from an institution (HR 1.319, 95% CI 1.095-1.563). Long-term survival of patients older than 65 years and of women with SAB is severely curtailed. PMID- 26873383 TI - The specificity of practice hypothesis in goal-directed movements: visual dominance or proprioception neglect? AB - The study aimed to examine whether modifying the proprioceptive feedback usually associated with a specific movement would decrease the dominance of visual feedback and/or decrease, which appears to be the neglect of proprioceptive feedback in ensuring the accuracy of goal-directed movements. We used a leg positioning recall task and measured the recall error after 15 and 165 acquisition trials performed with both vision and proprioception or proprioception only, under either a normal or a modified proprioception condition (i.e., with a 1-kg load attached to the participants' ankle). Participant learning was evaluated in transfer with proprioception only. In support of the specificity of practice hypothesis, the recall errors in acquisition were significantly smaller when practice occurred with both vision and proprioception, in either the loaded or the unloaded leg condition, and they increased significantly in transfer when vision was withdrawn. An important finding of the study highlighted that withdrawing vision after 165 acquisition trials had less deleterious effects on the recall errors when practice occurred under the loaded leg condition. Under that modified condition, recall errors in transfer were similar when practice occurred with and without vision, whereas larger errors were observed following practice with vision under the normal proprioceptive condition. Overall, these results highlighted the dominance of vision in ensuring accurate leg positioning recall and revealed that the dominance of vision is such that the processing of proprioceptive feedback may be neglected. Importantly, modifying the proprioceptive feedback has the advantage of reducing what appears to be the neglect of proprioceptive information when movement execution occurs in a visuo-proprioceptive context. Practical considerations for rehabilitation are discussed at the end of the manuscript. PMID- 26873382 TI - Diagnosis, antiviral therapy, and prophylaxis of varicella-zoster virus infections. AB - Varicella-zoster virus (VZV), an important member of the Herpesviridae family, is the etiological agent of varicella as primary infection and zoster as recurrence. An outstanding feature is the lifelong viral latency in dorsal root and cranial nerve ganglia. Both varicella and zoster are worldwide widespread diseases that may be associated with significant complications. However, there is a broad spectrum of laboratory methods to diagnose VZV infections. In contrast to many other viral infections, antiviral treatment of VZV infections and their prevention by vaccination or passive immunoprophylaxis are well established in medical practice. The present manuscript provides an overview about the basic knowledge of VZV infections, their laboratory diagnosis, antiviral therapy, and the prevention procedures, especially in Germany. PMID- 26873384 TI - I and Thou: learning the 'human' side of medicine. AB - This essay is a reflection on the doctor-patient relationship from the perspective of two medical students, which draws on the ideas of 20th-century philosopher Martin Buber. Although Buber never wrote about medicine directly, his 'philosophy of dialogue' raises fundamental questions about how human beings relate to one another, and can thus offer valuable insights into the nature of the clinical encounter. We argue that Buber's basic word pairs, 'I-You' and 'I It', provide a useful heuristic for understanding different modes of caring for patients, which we illustrate using examples of illness narratives from two literary works: Tolstoy's Ivan Ilych and Margaret Edson's Wit Our essay demonstrates how the humanities in general and philosophy in particular can inform a more humanistic practice for healthcare trainees and practicing clinicians alike. PMID- 26873385 TI - [Localized intermediate- to high-risk prostate cancer]. AB - BACKGROUND: National and international guidelines recommend radical prostatectomy (RP) and radiotherapy (EBRT) as standard treatment for intermediate- and high risk prostate cancer. Survival benefit of RP in prostate cancer has been proven in prospectively randomized trials. In contrast, the benefit of EBRT as well as the direct comparison of EBRT and RP have been investigated in several retrospective analyses, but are limited by typical problems associated with retrospective studies. RESULTS: Most of the studies comparing RP with EBRT favor RP with regard to overall survival and cancer-specific survival. Especially in young patients with high-grade prostate cancer, RP seems to be superior in comparison with EBRT. These patient are at high risk of a PSA recurrence and subsequently need an additional radiotherapy. Mortality and morbidity related to these both methods are low. Main complications of RP are urinary incontinence and erectile dysfunction. In contrast, rectal sequelae, erectile dysfunction, and irritative urinary symptoms are the main cause for postinterventional morbidity in patients after EBRT. PMID- 26873386 TI - Consecutive Observational Study to Validate EuroSCORE II Performances on a Single Center, Contemporary Cardiac Surgical Cohort. AB - OBJECTIVE: To compare and validate the original EuroSCORE risk stratification models with the renewed EuroSCORE II model in a contemporary cardiac surgical practice. DESIGN: A consecutive observational study to validate EuroSCORE II performances, conducted as retrospective analysis of prospectively collected data. SETTING: A tertiary university institute for cardiovascular diseases. PARTICIPANTS: Adult patients undergoing cardiac surgery between January and December 2012. METHODS: One thousand eight hundred sixty-four consecutive patients were scored preoperatively using additive and logistic EuroSCORE as well as EuroSCORE II. The discriminative power of the EuroSCORE models was tested by calculating the area under the receiver operating characteristic curve (AUC). The calibration of the models was assessed by Hosmer-Lemeshow statistics and with observed-to-expected mortality ratio. MEASUREMENTS AND MAIN RESULTS: The in hospital overall mortality was 3.65%, with predicted mortalities according to additive EuroSCORE, logistic EuroSCORE, and EuroSCORE II of 5.14%, 6.60%, and 3.51%, respectively. The observed-to-expected (O/E) mortality ratio confirmed good calibration for the entire cohort only for EuroSCORE II (1.05, 95% confidence interval 0.81 - 1.29). Hosmer-Lemeshow test confirmed overall good calibration only for additive EuroSCORE (p = 0.129). The EuroSCORE II confirmed very good discriminatory power for a prolonged intensive care unit (ICU) stay of>2 days and>5 days (AUCs>0.75). Acceptable discriminatory power was confirmed for a prolonged postoperative stay of>7 days and>12 days (AUCs>0.70). CONCLUSION: EuroSCORE II confirmed very good discriminatory capacity, good calibration ability (O/E mortality ratio), and good capability to predict prolonged ICU and postoperative stays in a contemporary patient cohort undergoing cardiac surgery. PMID- 26873387 TI - Unexpected Circulatory Collapse After Cardiac Paraganglioma Resection: Rescue With Intra-Aortic Balloon Pump and Extracorporeal Membrane Oxygenator. PMID- 26873388 TI - Arginine deiminase pathway genes and arginine degradation variability in Oenococcus oeni strains. AB - Trace amounts of the carcinogenic ethyl carbamate can appear in wine as a result of a reaction between ethanol and citrulline, which is produced from arginine degradation by some bacteria used in winemaking. In this study, arginine deiminase (ADI) pathway genes were evaluated in 44 Oenococcus oeni strains from wines originating from several locations in order to establish the relationship between the ability of a strain to degrade arginine and the presence of related genes. To detect the presence of arc genes of the ADI pathway in O. oeni, pairs of primers were designed to amplify arcA, arcB, arcC and arcD1 sequences. All strains contained these four genes. The same primers were used to confirm the organization of these genes in an arcABCD1 operon. Nevertheless, considerable variability in the ability to degrade arginine among these O. oeni strains was observed. Therefore, despite the presence of the arc genes in all strains, the expression patterns of individual genes must be strain dependent and influenced by the different wine conditions. Additionally, the presence of arc genes was also determined in the 57 sequenced strains of O. oeni available in GenBank, and the complete operon was found in 83% of strains derived from wine. The other strains were found to lack the arcB, arcC and arcD genes, but all contained sequences homologous to arcA, and some of them had also ADI activity. PMID- 26873389 TI - Effect of metal ions on autofluorescence of the dry rot fungus Serpula lacrymans grown on spruce wood. AB - This work describes autofluorescence of the mycelium of the dry rot fungus Serpula lacrymans grown on spruce wood blocks impregnated with various metals. Live mycelium, as opposed to dead mycelium, exhibited yellow autofluorescence upon blue excitation, blue fluorescence with ultraviolet (UV) excitation, orange red and light-blue fluorescence with violet excitation, and red fluorescence with green excitation. Distinctive autofluorescence was observed in the fungal cell wall and in granula localized in the cytoplasm. In dead mycelium, the intensity of autofluorescence decreased and the signal was diffused throughout the cytoplasm. Metal treatment affected both the color and intensity of autofluorescence and also the morphology of the mycelium. The strongest yellow signal was observed with blue excitation in Cd-treated samples, in conjunction with increased branching and the formation of mycelial loops and protrusions. For the first time, we describe pink autofluorescence that was observed in Mn-, Zn-, and Cu-treated samples with UV, violet or. blue excitation. The lowest signals were obtained in Cu- and Fe-treated samples. Chitin, an important part of the fungal cell wall exhibited intensive primary fluorescence with UV, violet, blue, and green excitation. PMID- 26873391 TI - Development and morphological changes in the vaginal closure membrane throughout gestation in Galea spixii (Rodentia: Caviidae). AB - Present research was carried out in order to perform the monitoring of development, recognizes the type of tissue and describes histological and cellular changes of the vaginal closure membrane (VCM) throughout pregnancy in Galea spixii. The results showed that at 20 days of gestation (DG), the VCM occludes completely the external vaginal ostium. Microscopically, the VCM presented juxtaposed cells, derived from the stratum germinative of the stratified epithelium of vaginal mucosa at 20 DG and areas with cell clusters with the presence of intercellular spaces in the final stages of pregnancy (40-50 DG). At 0 DG, the stratified epithelium of vaginal mucosa presented all strata but at 20 DG presented stratified epithelium without the stratum corneum and stratum granular and showed communicant junctions by desmosomes and interdigitations in the cell membrane compound the VCM. Gradually from 40 to 50 DG the stratum germinative became barely perceptible. Many cells showed apoptotic nuclei and emerged many intercellular spacing. So, the interdigitations and desmosomes were not observed. Here, it was demonstrated for the first time that the VCM is formed after the extinction of the stratum granular and corneum of the vaginal mucosa epithelium, with the proliferation of the cells of stratum germinative and communication and junction through desmosomes and interdigitations of these cells. At the end of pregnancy, cellular apoptosis; the spread of stratum germinative; and, absence of cellular communication and junction may be responsible for the weakening of the VCM and may assist the process of rupture of this membrane. PMID- 26873390 TI - Efficient DNP NMR of membrane proteins: sample preparation protocols, sensitivity, and radical location. AB - Although dynamic nuclear polarization (DNP) has dramatically enhanced solid-state NMR spectral sensitivities of many synthetic materials and some biological macromolecules, recent studies of membrane-protein DNP using exogenously doped paramagnetic radicals as polarizing agents have reported varied and sometimes surprisingly limited enhancement factors. This motivated us to carry out a systematic evaluation of sample preparation protocols for optimizing the sensitivity of DNP NMR spectra of membrane-bound peptides and proteins at cryogenic temperatures of ~110 K. We show that mixing the radical with the membrane by direct titration instead of centrifugation gives a significant boost to DNP enhancement. We quantify the relative sensitivity enhancement between AMUPol and TOTAPOL, two commonly used radicals, and between deuterated and protonated lipid membranes. AMUPol shows ~fourfold higher sensitivity enhancement than TOTAPOL, while deuterated lipid membrane does not give net higher sensitivity for the membrane peptides than protonated membrane. Overall, a ~100 fold enhancement between the microwave-on and microwave-off spectra can be achieved on lipid-rich membranes containing conformationally disordered peptides, and absolute sensitivity gains of 105-160 can be obtained between low-temperature DNP spectra and high-temperature non-DNP spectra. We also measured the paramagnetic relaxation enhancement of lipid signals by TOTAPOL and AMUPol, to determine the depths of these two radicals in the lipid bilayer. Our data indicate a bimodal distribution of both radicals, a surface-bound fraction and a membrane-bound fraction where the nitroxides lie at ~10 A from the membrane surface. TOTAPOL appears to have a higher membrane-embedded fraction than AMUPol. These results should be useful for membrane-protein solid-state NMR studies under DNP conditions and provide insights into how biradicals interact with phospholipid membranes. PMID- 26873392 TI - Effectiveness of Anise Oil for Treatment of Mild to Moderate Depression in Patients With Irritable Bowel Syndrome: A Randomized Active and Placebo Controlled Clinical Trial. AB - Depression is a prevalent disorder among patients suffering from irritable bowel syndrome. The current study was performed to evaluate the effect of a traditional Persian medicine product, anise oil, in removing the symptoms of mild to moderate depression in patients with irritable bowel syndrome. In a randomized double blinded active and placebo controlled clinical trial, 120 participants with mild to moderate depression according to the Beck Depression Inventory-II total scores were categorized into 3 equal groups and received anise oil, Colpermin, and placebo. The results at the end of trial (week 4) and follow-up (week 6) demonstrated significant priority against active and placebo groups. Although the mechanism is unknown yet, anise oil could be a promising choice of treatment for depressed patients with irritable bowel syndrome. PMID- 26873394 TI - Targeted thrombolysis of tissue plasminogen activator and streptokinase with extracellular biosynthesis nanoparticles using optimized Streptococcus equi supernatant. AB - Extracellular biosynthesis of nanoparticles have many important advantages such as well dispersed in aqueous solutions, low energy requirements, ecofriendly, non toxic, low-costs and non-flocculate. This technique have shown significant promise as targeted drug delivery applications. In this investigation, for the first time, we examine the efficacy of targeted therapeutic delivery with t-PA and SK immobilized to biosynthesis of nanoparticles (CuNP) by using Streptococcus equi strains isolated from the horses of Iran and their ability to produce metallic nanoparticles. Also we compared them with their chemical synthesis. The S. equi was screened for its ability to produce MNPs. The minimum size and shapes (23-89 nm) are presented in the formation with good dispersion and high stability. Response Surface methodology was applied for the optimized production of biological CuNPs. The growth factors like pH, temperature and incubation time was changed. The optimum conditions to obtain CuNPs were found with the culture conditions of pH 7.5 in 120 h at 35 degrees C. To determine some of MNPs structural properties UV-vis absorption spectrophotometer, FTIR, XRD and SEM has characterized. The results provided some parameters may impact on the formation of biological MNPs. Lastly, these MNPs were conjugated with t-PA and SK, as a drug carrier. In addition, effective thrombolysis with magnet-guided SiO2CuNPs tPA-SK is demonstrated in rat embolism model where 18.6% of the regular t-PA dose and 15.78% of SK dose restored and 15-25 min reductions in blood clot lysis time were observed compared with runs with free t-PA and without magnet-guided and using the same drug dosage. The comparison between CuNPs with MNPs shows that thrombolysis had not been directed to the type of magnetic carrier under the magnetic guide. PMID- 26873395 TI - Does 2,4-dichlorophenoxyacetic acid (2,4-D) induce genotoxic effects in tissue cultured Allium roots? AB - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a synthetic plant growth regulator that is highly toxic to most broad leaved plants and relatively nontoxic to monocotyledonous plants; is frequently used as weed killer. The study aimed to investigate cytogenetic effects of different concentrations of 2,4-D (0.67, 1.34, 2.01, 2.68, 3.35 and 4.02 mg/L) on Allium cepa bulblets' root tips treated for 24 and 48 h. The results showed six types of structural aberrations: C-mitosis, stickiness, laggards, bridges, fragments and multipolarity that varied numerically compared to control. It significantly affected mitotic index (MI) at 24 and 48 h treatment. In the Allium test, MI increased significantly at three lower concentrations (0.67, 1.34, 2.01 mg/L) after treatment with 2,4-D for 24 h and decreased significantly at higher concentration. Whereas, 2,4-D treatment for 48 h increased MI at all concentrations with significantly decreased MI at the highest concentration. The experiment was extended using comet test that did not reveal significant difference among treatments except for application of 4.02 mg/L 2,4-D for 48 h; where cell damages were verified by comet test. Rest of the concentrations for any duration of time were not damaging and toxic to cells. The results showed, visible mitodepressive action of 4.02 mg/L 2,4-D when treated for 48 h that had tendency to become toxic if the roots had been in touch with 2,4-D for a longer time. PMID- 26873393 TI - Non-glycosidic compounds can stimulate both human and mouse iNKT cells. AB - Invariant natural killer T (iNKT) cells recognize CD1d/glycolipid complexes and upon activation with synthetic agonists display immunostimulatory properties. We have previously described that the non-glycosidic CD1d-binding lipid, threitolceramide (ThrCer) activates murine and human iNKT cells. Here, we show that incorporating the headgroup of ThrCer into a conformationally more restricted 6- or 7-membered ring results in significantly more potent non glycosidic analogs. In particular, ThrCer 6 was found to promote strong anti tumor responses and to induce a more prolonged stimulation of iNKT cells than does the canonical alpha-galactosylceramide (alpha-GalCer), achieving an enhanced T-cell response at lower concentrations compared with alpha-GalCer both in vitro, using human iNKT-cell lines and in vivo, using C57BL/6 mice. Collectively, these studies describe novel non-glycosidic ThrCer-based analogs that have improved potency in iNKT-cell activation compared with that of alpha-GalCer, and are clinically relevant iNKT-cell agonists. PMID- 26873396 TI - Consideration for Esophagectomy in Patients with Prior Bariatric Surgery. AB - Bariatric surgery is frequently performed for the treatment of severe obesity. Esophageal cancer has been reported to occur in patients who had prior bariatric surgery. Due to the anatomic alterations associated with bariatric surgery, esophageal resection requires an understanding of certain technical considerations. This paper describes the technical considerations in performance of an esophageal resection in patients who had prior sleeve gastrectomy or Roux en-Y gastric bypass. PMID- 26873397 TI - Do Complications Alter Postoperative Weight Loss 1 Year After Primary and Revisional Roux-en-Y Gastric Bypass? AB - BACKGROUND: Around 10 % of the bariatric surgery patients experience postoperative complications (<30 days). It could be hypothesized that complications influence postoperative weight loss, which is one of the most important endpoints of bariatric surgery. Therefore, this study inventoried the effect of complications on postoperative weight loss. METHODS: A consecutive database including patients who were operated from November 2007 onwards was retrospectively reviewed. All short-term complications were classified according to the Clavien-Dindo classification. Weight loss was assessed at 6 and 12 months postoperatively. RESULTS: A total of 1130 patients underwent either primary (n = 907, 80.3 %) or revisional (n = 233, 19.7 %) surgery till October 2013. Short term complications occurred in 115 (10.2 %) patients, of whom 48 (41.7 %) had a severe (Clavien-Dindo >= 3) complication. One year post surgery, 184 patients (16.3 %) were lost to follow-up. Patients with a short-term complication had a higher percentage of excess weight loss (%EWL) at 6 months (58.6 (SD 16.6) versus 52.9 (SD 17.6), p = 0.003) and 1 year (71.9 (SD 22.3) versus 65.9 (SD 21.3), p = 0.017) of follow-up. Although a trend was seen toward higher BMI loss and total weight loss (TWL) after 6 months, no effect was seen 1 year postoperatively. In multivariable linear regression analysis, complications were not a significant predictor for 1-year %EWL. CONCLUSIONS: Although short-term complications alter 1 year %EWL, no effect was seen on BMI loss and TWL. In addition, complications were not a predictor in a multivariable linear regression model for 1-year %EWL. It can be concluded that short-term complications do not impair weight loss after Roux-en-Y gastric bypass. PMID- 26873398 TI - Sparse estimation of Cox proportional hazards models via approximated information criteria. AB - We propose a new sparse estimation method for Cox (1972) proportional hazards models by optimizing an approximated information criterion. The main idea involves approximation of the l0 norm with a continuous or smooth unit dent function. The proposed method bridges the best subset selection and regularization by borrowing strength from both. It mimics the best subset selection using a penalized likelihood approach yet with no need of a tuning parameter. We further reformulate the problem with a reparameterization step so that it reduces to one unconstrained nonconvex yet smooth programming problem, which can be solved efficiently as in computing the maximum partial likelihood estimator (MPLE). Furthermore, the reparameterization tactic yields an additional advantage in terms of circumventing postselection inference. The oracle property of the proposed method is established. Both simulated experiments and empirical examples are provided for assessment and illustration. PMID- 26873399 TI - Genetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease. AB - Genome-wide association studies and candidate gene studies have informed our understanding of factors contributing to the well-recognized interindividual variation in the progression and outcomes of alcoholic liver disease and nonalcoholic fatty liver disease. We discuss the mounting evidence for shared modifiers and common pathophysiological processes that contribute to development of both diseases. We discuss the functions of proteins encoded by risk variants of genes including patatin-like phospholipase domain-containing 3 and transmembrane 6 superfamily member 2, as well as epigenetic factors that contribute to the pathogenesis of alcoholic liver disease and nonalcoholic fatty liver disease. We also discuss important areas of future genetic research and their potential to affect clinical management of patients. PMID- 26873400 TI - Clinical Implications of Concomitant Alcohol Use, Obesity, and Viral Hepatitis. PMID- 26873402 TI - Predictors and signatures of recovery from neglect in acute stroke. AB - OBJECTIVE: Spatial neglect can either spontaneously resolve or persist after stroke; the latter is associated with a poorer outcome. We aimed to investigate the neural correlates and predictors of favorable versus poor recovery from neglect in acute stroke. METHODS: In addition to neuropsychological testing, we explored task-related functional magnetic resonance imaging activation and functional connectivity in 34 patients with neglect and/or extinction. Patients were examined at 2 to 3 days (acute phase I) and 8 to 10 days (acute phase II), and some of them at 4 to 6 months (chronic phase) poststroke. RESULTS: Course of recovery was predicted by the strength of functional connectivity between the right parietal and left prefrontal and parietal regions, as early as acute phase I. During acute phase II, favorable recovery from neglect was associated with increased activation in the left prefrontal and right parietal regions, an effect not observed at any time point in patients with poor acute recovery. The extent of neglect amelioration correlated with activation gain in the right attention centers; stronger activation of their left functional homologues correlated with better spatial processing in the neglected hemispace during both of the acute examination phases. INTERPRETATION: System excitability and early recruitment of contralesional functional homologues represented specific features of favorable recovery in acute stroke. In severe strokes leading to neglect, contralesional functional homologues support recovery by modulating the preserved ipsilesional network, and initial functional connectivity between them might predict recovery course and help to identify patients with potentially poor recovery requiring more intensive early rehabilitation. PMID- 26873403 TI - Use of the human hepcidin gene to build a positive-selection vector for periplasmic expression in Escherichia coli. AB - Recombinant proteins are often produced in the periplasm of Escherichia coli because this facilitates the purification process. The oxidizing environment favors the formation of disulfide bridges. We showed that the periplasmic expression of the human hormone hepcidin 25 (Hep25) fused to the maltose-binding protein (MBP) resulted in cell death. This toxicity was not observed when MBP Hep25 accumulated in the bacterial cytoplasm, or when Hep25 was addressed to the periplasm without the MBP tag. We then modified the periplasmic expression vector pMALp2E to create pMALp2EH, a positive-selection vector with Hep25 as counterselection gene. PMID- 26873401 TI - Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population. AB - BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS: A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers. PMID- 26873404 TI - A global assessment of a large monocot family highlights the need for group specific analyses of invasiveness. AB - Significant progress has been made in understanding biological invasions recently, and one of the key findings is that the determinants of naturalization and invasion success vary from group to group. Here, we explore this variation for one of the largest plant families in the world, the Araceae. This group provides an excellent opportunity for identifying determinants of invasiveness in herbaceous plants, since it is one of the families most popular with horticulturalists, with species occupying various habitats and comprising many different life forms. We first developed a checklist of 3494 species of Araceae using online databases and literature sources. We aimed to determine whether invasiveness across the introduction-naturalization-invasion continuum is associated to particular traits within the family, and whether analyses focussed on specific life forms can reveal any mechanistic correlates. Boosted regression tree models were based on species invasion statuses as the response variables, and traits associated with human use, biological characteristics and distribution as the explanatory variables. The models indicate that biological traits such as plant life form and pollinator type are consistently strong correlates of invasiveness. Additionally, large-scale correlates such as the number of native floristic regions and number of introduced regions are also influential at particular stages in the invasion continuum. We used these traits to build a phenogram showing groups defined by the similarity of characters. We identified nine groups that have a greater tendency to invasiveness (includingAlocasia, the Lemnoideae andEpipremnum). From this, we propose a list of species that are not currently invasive for which we would recommend a precautionary approach to be taken. The successful management of plant invasions will depend on understanding such context-dependent effects across taxonomic groups, and across the different stages of the invasion process. PMID- 26873405 TI - Understanding the nanoparticle-protein corona complexes using computational and experimental methods. AB - Nanoparticles (NP) have capability to adsorb proteins from biological fluids and form protein layer, which is called protein corona. As the cell sees corona coated NPs, the protein corona can dictate biological response to NPs. The composition of protein corona is varied by physicochemical properties of NPs including size, shape, surface chemistry. Processing of protein adsorption is dynamic phenomena; to that end, a protein may desorb or leave a surface vacancy that is rapidly filled by another protein and cause changes in the corona composition mainly by the Vroman effect. In this review, we discuss the interaction between NP and proteins and the available techniques for identification of NP-bound proteins. Also we review current developed computational methods for understanding the NP-protein complex interactions. PMID- 26873406 TI - Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A. AB - Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 -> R or H142 -> F or H142 -> A substitutions resulted in non-infectious FMDV, H142 -> D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A. PMID- 26873407 TI - Eimeria tenella: a novel dsRNA virus in E. tenella and its complete genome sequence analysis. AB - Protozoa double-stranded (ds) RNA viruses have been described in Trichomonas, Giardia, and Leishmania. In this study, dsRNA and virus-like particles (approximately 30 nm in diameter) were discovered in Eimeria tenella sporulated oocysts. The complete genome of this novel dsRNA virus was sequenced using a three-step strategy. The sequencing results showed that the complete genome sequence was 6006 bp containing two open reading frames (ORFs) (2367 bp for ORF1 and 3216 bp for ORF2) with a five-nucleotide overlap (UGA/UG). The predicted ORF1 and ORF2 encoded a putative capsid protein of 788 amino acids (84.922 kDa) and a putative RNA-dependent RNA polymerase (RdRp) protein of 1071 amino acids (118.190 kDa). BLASTp analysis showed that the amino acid sequences for the E. tenella virus shared similarity with the E. brunetti RNA virus, with 29% homology in capsid proteins and 36% in RDRP proteins. The two untranslated regions were 349 bp (5' UTR) and 78 bp (3' UTR). The complete genome sequence of the E. tenella virus resembled characteristics of the Totiviridae family, indicating that this virus was a novel member of Totiviridae. Surprisingly, phylogenetic analysis showed that the E. tenella virus, E. brunetti RNA virus 1, and Mycoviruses were clustered into the genus Victorivirus and separated from the reported protozoa viruses, strongly suggesting a novel Eimeriaviruses subgenus. To the best of our knowledge, this is the first report for the complete genome sequence of the E. tenella virus. Using the nomenclature generally adopted for viruses, this new isolate was named E. tenella RNA virus 1. This study provides a foundation basis for further research on the biological characteristics of Eimeriaviruses. PMID- 26873408 TI - Clenbuterol causing non-ST-segment elevation myocardial infarction in a teenage female desiring to lose weight: case and brief literature review. PMID- 26873409 TI - Cervical spine immobilization may be of value following firearm injury to the head and neck. AB - BACKGROUND: Penetrating injuries to the head and neck may not be able to cause unstable fractures without concomitant spinal cord injury, rendering prehospital spinal immobilization (PHSI) ineffectual, and possibly harmful. However, this premise is based on reports including predominantly chest and abdominal injuries, which are unlikely to cause cervical spine (CS) injuries. METHODS: We performed a retrospective review of all patients presenting with a penetrating wound to the head or neck over a 4-year period at an urban, level 1 trauma center to determine if there was a benefit of PHSI. RESULTS: One hundred seventy-two patients were identified, of which 16 (9.3%) died prior to CS evaluation. Of 156 surviving patients, mechanism was gunshot wound (GSW) in 36 (28%) and stab wound (SW) in 120 (72%). Fifty-eight patients had PHSI placed (37%), and GSW patients' odds of having PHSI were greater than SW patients (OR 2.3; CI 1.08-4.9). Eight of 156 surviving patients eventually died (5.1%), and the odds of mortality were greater among those that had PHSI than those without (OR 5.54; CI 1.08-28.4). Six (3.8%; 5 GSW, 1 SW) patients had a CS fracture. Two GSW patients (5.6%) had unstable CS fractures with a normal neurological exam at initial evaluation. CONCLUSIONS: Of patients with a GSW to the head or neck that survived to be evaluated, 5.6% had unstable fractures without an initial neurologic deficit. PHSI may be appropriate in this population. Further studies are warranted prior to a determination that PHSI is unnecessary in penetrating head and neck injuries. PMID- 26873410 TI - Combined Treatment with Systemic and Local Delivery of Substance P Coupled with Self-Assembled Peptides for a Hind Limb Ischemia Model. AB - When treating critical limb ischemia caused by various chronic diseases such as diabetes and hypertension, it is essential to effectively induce angiogenesis to supply blood flow to the ischemic region. Recently, several studies have investigated the effects of cell transplantation with mesenchymal stem cells (MSCs) as a therapeutic modality for treating these ischemic diseases. However, some limitations have to be overcome first before cell transplantation can be considered as a promising treatment for ischemic diseases, such as limited sources of cells and the low survival rates of transplanted cells. In this study, self-assembled peptide (SAP) hydrogels coupled with substance P (SP) were used to induce the recruitment of MSCs in an injury site in mouse ischemic hind limb models without exogenous injection of cells. In addition, a combined delivery strategy consisting of local and systemic delivery of SP was used to examine the synergetic effects of systemic and local deliveries. Limb ischemia in athymic mice was induced through the femoral artery by ligating and resecting its branches, and SAP coupled with SP (bioactive SAPs) was injected into the ischemic region. The therapeutic effects on the ischemic region were observed in terms of cell migration, fibrosis, apoptosis, and angiogenesis in each experimental group. The combined therapeutic delivery system resulted in the recruitment of more cells for effective regeneration, promotion of neovascularization, and formation of mature vessels for tissue perfusion and inhibition of fibrosis and cell apoptosis than a single treatment. In conclusion, it was confirmed that the combined therapy of local and system delivery of the SP-conjugated peptide hydrogels and SP could effectively enhance the mobilization of host cells related to angiogenesis to injured tissue, and consequently, they could be useful in treating ischemic diseases without cell transplantation. PMID- 26873411 TI - Cross-fostering alters advertisement vocalizations of grasshopper mice (Onychomys): Evidence for the developmental stress hypothesis. AB - Nutritional stress can have lasting impacts on the development of traits involved in vocal production. Cross-fostering experiments are often used to examine the propensity for vocal learning in a variety of taxa, but few studies assess the influence of malnourishment that can occur as a byproduct of this technique. In this study, we reciprocally cross-fostered sister taxa of voluble grasshopper mice (genus Onychomys) to explore their propensity for vocal learning. Vocalizations of Onychomys leucogaster did not differ between control and cross fostered animals, but cross-fostered Onychomys arenicola produced vocalizations that were higher in frequency in a direction away from tutors. These same animals exhibited a transient reduction in body mass early in development, indicative of malnutrition. Our findings simultaneously refute vocal learning and support the developmental stress hypothesis to highlight the importance of early ontogeny on the production of vocalizations later in life. PMID- 26873413 TI - Effect of hyperprolactinemia on PRL-receptor expression and activation of Stat and Mapk cell signaling in the prostate of long-term sexually-active rats. AB - The abnormal elevation of serum PRL, referred to as hyperprolactinemia (HyperPRL), produces alterations in several reproductive parameters of male rats such as penile erection or decreased tendency to reach ejaculation. Additionally, this situation produces a significant modification of prostate histology, as observed in the epithelial structure and alveolar area, which could reach a level of hyperplasia in the long-term. In this tissue, HyperPRL produces an increase in expression of PRL receptors and activation of the Stat3 signaling pathway that is correlated with the evolution of prostate pathologies. However, the impact of HyperPRL in long-term sexually active male rats is unknown. In this work, using constantly copulating Wistar male rats with induced HyperPRL, we analyzed the level of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Two procedures to induce HyperPRL were employed, comprising daily IP administration or adenohypophysis transplant, and although neither affected the execution of sexual behavior, the serum PRL profile following successive ejaculations was affected. Messenger RNA expression of the short and long isoforms of the PRL receptor at the ventral prostate was affected in different ways depending on the procedure to induce HyperPRL. The ventral prostate did not show any modification in terms of activation of the pStat5 signaling pathway in subjects with daily administration of PRL, although this was significantly increased in ADH transplanted subjects in the second and fourth consecutive ejaculation. A similar profile was found for the pStat3 pathway which additionally showed a significant increase in the third and fourth ejaculation of daily-injected subjects. The Mapk signaling pathway did not show any modifications in subjects with daily administration of PRL, but showed a significant increase in the second and third ejaculations of subjects with ADH transplants. Thus, although sexual behavior was not modified, HyperPRL modified the expression of PRL receptors and the activation of signal pathways in the prostate tissue. Hence, it is probable that prostatic alterations precede the sexual behavioral deficits observed in subjects with HyperPRL. PMID- 26873412 TI - Maternal high-fat diet increases independent feeding in pre-weanling rat pups. AB - In laboratory settings, the adult offspring of rodent dams that are maintained on high-fat diet (HFD) before conception and/or during pregnancy/lactation display an increased incidence of obese phenotypic markers, including increased body weight and adiposity, reduced leptin sensitivity, and impaired glucose tolerance. In rat pups raised by dams consuming HFD, these obese markers emerge during the first postnatal week. Since the week-old offspring of HFD dams consume excess amounts of milk during experimental tests of independent feeding (i.e., intake away from the dam), we hypothesized that maternal diet affects suckling and/or independent ingestion by pups in the home-cage environment. In the present study, this hypothesis was tested by conducting detailed analyses of ingestive behaviors expressed by pups in the home cage. Pups raised by dams consuming HFD displayed an earlier onset of independent feeding and more amounts of calorie intake from solid food during the third postnatal week compared to pups raised by dams consuming regular chow, with no diet-related differences in suckling behavior. Independent ingestion by pups in both diet groups was most frequently observed after nursing, with offspring of HFD dams engaged more frequently in post-nursing independent feeding episodes compared to offspring of chow-fed dams, particularly when the prior nursing episode was nutritive (i.e., including milk receipt by pups). We conclude that early-life exposure to HFD enhances the facilitative effect of nutritive suckling on independent feeding in pups, promoting increased caloric intake from solid food in the home-cage environment. PMID- 26873415 TI - Indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3-triazoles: Synthesis, characterization and evaluation of anticancer, antibacterial, and DNA cleavage activities. AB - A series of new indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3 triazoles (I(1)-I(6) and I(7)-I(12)) were synthesized and screened for their anticancer (in vitro and in vivo), antibacterial, and DNA cleavage activities. All the synthesized compounds were characterized by spectral studies. The in vitro anticancer screening results revealed that compound I(12) has registered potential activity against MCF-7, HeLa and HEK293 as compared with the standard reference drug Cisplatin. Remaining compounds have exhibited moderate to good activity against three cancer cell lines. The antibacterial activity screening results revealed that compounds, I(6) and I(12) have registered excellent inhibition against Escherichia coli and Bacillus subtilis in comparison with the standard drug Streptomycin. Compounds I(2) and I(11) have partially cleaved the DNA at 100 MUg mL(-1) concentration. PMID- 26873414 TI - Synthesis and evaluation of anticancer and antiobesity activity of 1-ethoxy carbonyl-3,5-bis (3'-indolyl methylene)-4-pyperidone analogs. AB - A series of eleven novel bisindole derivatives were synthesized and screened for anticancer and antiobesity potentials in in vitro mode. The reaction of 1-ethoxy carbonyl 4-pyperidone 1a with indole-3-carboxaldehyde 1b in presence of catalytic amount of piperidine gave 2 which was N-alkylated with different benzyl halides in the presence of potassium carbonate to afford compounds 3a-3k in quantitative yields. Among the compounds tested for anticancer activity against different human cancer cell lines, 3f significantly inhibited HepG2 cell line (IC50 7.33 MUM) when compared with standard doxorubicin (IC50 10.15 MUM). Compounds 3e (IC50 2.75 MUM), 3f (IC50 4.21 MUM) and 3i (IC50 15.98 MUM) showed better activity than the standard curcumin (IC50 23.54 MUM) against A549 cell line. Also, among the synthesized compounds, 3g (IC50 14.89 MUM), 3c (IC50 56.41 MUM) and 3i (IC50 30.88 MUM) have potentially inhibited enzyme lipase when compared to standard Orlistat (IC50 62.25 MUM). In in silico docking assays, piperidones 3e, 3f, 3i, 3c and 3a showed higher binding affinity towards anti-cancer target of A549 (3e: 11.1, 3f: -10.3, 3c: -11.3, 3i: -11.2 kcal/mol), HepG2 (3f: -10.5 kcal/mol), HeLa (3d: -10.0 kcal/mol) and SKOV3 (3f: -8.4 kcal/mol) cell lines better than standard drug doxorubicin. Docking to lipase protein for compounds 3i, 3g and 3c showed scores of -11.1, -10.7 and -10.5 kcal/mol when compared to that of standard drug Orlistat with -6.9 kcal/mol. PMID- 26873416 TI - Synthesis of hybrid 4-deoxypodophyllotoxin-5-fluorouracil compounds that inhibit cellular migration and induce cell cycle arrest. AB - A series of deoxypodophyllotoxin-5-fluorouracil hybrid compounds were synthesized, and their cytotoxic activity was evaluated using four human cancer cell lines (HeLa, A549, HCT-8, and HepG2) and the human normal cell line WI-38. The synthesized compounds exhibited greater cytotoxic activity in tumor cells and reduced toxicity in the normal cell line compared with the anticancer drug VP-16 and 5-FU. Additionally, the most potent of these compounds-4'-O-demethyl-4 deoxypodophyllotoxin-4'-yl 4-((6-(2-(5-fluorouracil-yl) acetamido) hexyl) amino) 4-oxobutanoate (compound 22)-induced cell-cycle arrest in the G2/M phase by regulating levels of cdc2, cyclinB1, and p-cdc2 in A549 cells. Furthermore, compound 22 may inhibited the migration of A549 cells via down-regulation of MMP 9 and up-regulation of TIMP-1. PMID- 26873417 TI - Intestinal ischemia secondary to mesenteric vessel avulsion in abdominal trauma. PMID- 26873418 TI - First resuscitation of critical burn patients: progresses and problems. AB - Currently, the aim of the resuscitation of burn patients is to maintain end-organ perfusion with fluid intake as minimal as possible. To avoid excess intake, we can improve the estimation using computer methods. Parkland and Brooke are the commonly used formulas, and recently, a new, an easy formula is been used, i.e. the 'Rule of TEN'. Fluid resuscitation should be titrated to maintain the urine output of approximately 30-35 mL/h for an average-sized adult. The most commonly used fluids are crystalloid, but the phenomenon of creep flow has renewed interest in albumin. In severely burn patients, monitoring with transpulmonary thermodilution together with lactate, ScvO2 and intraabdominal pressures is a good option. Nurse-driven protocols or computer-based resuscitation algorithms reduce the dependence on clinical decision making and decrease fluid resuscitation intake. High-dose vitamin C, propranolol, the avoidance of excessive use of morphine and mechanical ventilation are other useful resources. PMID- 26873419 TI - Modified glycan models of pig-to-human xenotransplantation do not enhance the human-anti-pig T cell response. AB - Genetically modified porcine models of pig-to-human xenotransplantation offer the most immediate answer to a growing shortage of available solid organs. Recently a modified porcine glycan model has been discovered that reduces human antibody binding to levels comparable with allograft standards. As this background provides an answer to the problem of acute humoral xenograft rejection (AHXR), it is important to consider the impact these modifications have on measures of cell mediated rejection. The objective of this study was to examine the impact of currently relevant glycan knockout models of pig-to-human xenotransplantation in a lymphocyte proliferation assay. To accomplish these goals, genetically modified pigs were created through CRISPR/Cas9-directed silencing of the GGTA1, and CMAH genes. Peripheral blood mononuclear cells (PBMCs) and spleen cells were obtained from these animals and used as a source of stimulation for human responders in one-way mixed lymphocyte reactions. The response was tested in the presence and absence of clinically available immunomodifiers. CONCLUSIONS: Clinically relevant glycan knockout models of pig-to-human xenotransplantation do not enhance the human-anti-pig cellular response. Currently available and conventional immunosuppression has the capacity to mediate the human xenogeneic T cell response to these knockout cells. PMID- 26873420 TI - Auditory-perceptual Evaluation of Normal and Dysphonic Voices Using the Voice Deviation Scale. AB - OBJECTIVE: This study aims to (1) determine the cutoff values of the overall severity (OS) of vocal deviation on the visual analog scale (VAS) based on the ratings of the numerical scale (NS); and (2) verify the power of discrimination of these cutoff values according to different degrees of vocal deviation. STUDY DESIGN: This is a prospective study. METHODS: The auditory-perceptual evaluation was performed by four speech-language pathologists who used two protocols with different scalar properties: the VAS and the 4-point NS. Vocal samples from142 women and 69 men, plus 10% of repetition, with and without vocal complaints, ranging from 19 to 60 years were included. The analyzed speaking task was the counting from 1 to 10. For both protocols, the judges rated the OS. RESULTS: Based on the correspondence between the two scales, the cutoff values of the OS on the VAS obtained were 35.5, 50.5, and 90.5 points. The 35.5 value corresponds to the cutoff point between normal variability and mild/moderate vocal deviations; the 50.5 value corresponds to the cutoff point between mild/moderate and moderate vocal deviations; the 90.5 value corresponds to the cutoff point between moderate and severe deviations. Areas under the receiver operating characteristic curve for the three cutoff values were 0.918, 0.948, and 0.970, respectively. CONCLUSIONS: The cutoff values of the OS on the VAS were obtained, and the areas under the ROC curve showed that all the three cutoff points had excellent accuracy that represents a higher power of discrimination of different degrees of vocal deviations. PMID- 26873421 TI - Photographic Objective Alterations for Laryngopharyngeal Reflux Diagnosis. AB - OBJECTIVE: Diagnosis of laryngopharyngeal reflux (LPR) in clinical practice is generally made subjectively based on history, symptoms, and endoscopic assessment. This study presents the diagnostic role of the digital photographic assessment of the laryngopharyngeal region for LPR. METHODS: Seventy-two patients with LPR symptoms and 35 healthy volunteers were evaluated using the Reflux Finding Scores (RFS) and the Reflux Symptom Index (RSI). The results of these scales were recorded in 72 patients representing group 1 with LPR diagnosis; they returned after 1 and 2 months of treatment as groups 2 and 3, respectively. Thirty-five volunteers represented group 4. Laryngopharyngeal regions of all subjects were examined and photographed endoscopically. Red, green, and blue (RGB) values of particular oropharyngeal and laryngeal points were measured. RESULTS: RSI and RFS values of group 1 were significantly different from the other three groups, as were the scores of group 2; however, the comparison of the RSI and RFS values of groups 3 and 4 did not reveal a statistically significant difference. Laryngopharyngeal RGB values also duplicated statistical significance as above. CONCLUSION: Measurement of RGB values can be a cheap and easy-to-use method to quickly provide objective and corroborative information to help in the diagnosis of LPR in conjunction with subjective methods. PMID- 26873422 TI - Vocal Responses in Heighted States of Arousal. AB - OBJECTIVES: The purpose of this study was to investigate electroglottography (EGG) contact quotient modulation with emotional state in the presence of increased arousal. STUDY DESIGN: A within-subject reversal paradigm using multiple experimental conditions. METHODS: A total of 11 healthy undergraduate students underwent emotion induction with intermittent startles to increase physiologic arousal. During emotion induction, they vocalized on the vowel /u/ while EGG was recorded. RESULTS: EGG contact quotient was significantly greater for negative emotions compared with positive emotions with increased arousal commensurate with past research. In addition, overall EGG contact quotient was greater with elevated arousal. However, the effect sizes were small. CONCLUSIONS: EGG contact quotient appears to increase with elevated arousal and be greater for negative mood states than positive mood states confirming that emotion states directly influence vocal functioning. PMID- 26873423 TI - The Effect of Hydration on the Voice Quality of Future Professional Vocal Performers. AB - OBJECTIVES: The application of systemic hydration as an instrument for optimal voice quality has been a common practice by several professional voice users over the years. Although the physiological action has been determined, the benefits on acoustic and perceptual characteristics are relatively unknown. The present study aimed to determine whether systemic hydration has beneficial outcomes on the voice quality of future professional voice users. STUDY DESIGN: A within-subject, pretest posttest design is applied to determine quantitative research results of female singing students between 18 and 32 years of age without a history of voice pathology. METHODS: Acoustic and perceptual data were collected before and after a 2-hour singing rehearsal. The difference between the hypohydrated condition (controlled) and the hydrated condition (experimental) and the relationship between adequate hydration and acoustic and perceptual parameters of voice was then investigated. RESULTS: A statistical significant (P = 0.041) increase in jitter values were obtained for the hypohydrated condition. Increased maximum phonation time (MPT/z/) and higher maximum frequency for hydration indicated further statistical significant changes in voice quality (P = 0.028 and P = 0.015, respectively). CONCLUSION: Systemic hydration has positive outcomes on perceptual and acoustic parameters of voice quality for future professional singers. The singer's ability to sustain notes for longer and reach higher frequencies may reflect well in performances. Any positive change in voice quality may benefit the singer's occupational success and subsequently their social, emotional, and vocational well-being. More research evidence is needed to determine the parameters for implementing adequate hydration in vocal hygiene programs. PMID- 26873424 TI - Comparison of severity classification in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis in a nationwide, prospective, inception cohort study. AB - OBJECTIVE: To compare disease severity classification systems for six-month outcome prediction in patients with antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). METHODS: Patients with newly diagnosed AAV from 53 tertiary institutions were enrolled. Six-month remission, overall survival, and end-stage renal disease (ESRD)-free survival were evaluated. RESULTS: According to the European Vasculitis Study Group (EUVAS)-defined disease severity, the 321 enrolled patients were classified as follows: 14, localized; 71, early systemic; 170, generalized; and 66, severe disease. According to the rapidly progressive glomerulonephritis (RPGN) clinical grading system, the patients were divided as follows: 60, grade I; 178, grade II; 66, grade III; and 12, grade IV. According to the Five-Factor Score (FFS) 2009, 103, 109, and 109 patients had <=1, 2, and >=3 points, respectively. No significant difference in remission rates was found in any severity classification. The overall and ESRD-free survival rates significantly differed between grades I/II, III, and IV, regardless of renal involvement. Severe disease was a good predictor of six-month overall and ESRD free survival. The FFS 2009 was useful to predict six-month ESRD-free survival but not overall survival. CONCLUSIONS: The RPGN grading system was more useful to predict six-month overall and ESRD-free survival than the EUVAS-defined severity or FFS 2009. PMID- 26873425 TI - Utility of High-Output His Pacing during Difficult AV Node Ablation. An Underutilized Strategy. AB - Atrioventricular (AV) node ablation is a commonly performed procedure for patients with chronic drug refractory atrial fibrillation (AF) with episodes of rapid ventricular response. We report on a 72-year-old man who had difficulty managing chronic drug refractory AFs with frequent hospitalizations for rapid ventricular rate. The patient was taken to the electrophysiology laboratory for AV node ablation. Extensive mapping and localization techniques of the compact AV node and ablation in the region were unsuccessful. Subsequently, high-output His bundle pacing using 20 mA at 2 ms of output energy was performed in an attempt to localize the His bundle in areas where high-output pacing resulted in a narrower QRS complex. Further ablations in the areas where pacing produced a narrower QRS complex resulted in complete heart block. This case highlights the importance of using this simple pacing maneuver to achieve complete heart block in patients in whom standard strategies to localize and ablate the compact AV node are unsuccessful. PMID- 26873426 TI - Therapeutic effects of quercetin on early inflammation in hypertriglyceridemia related acute pancreatitis and its mechanism. AB - OBJECTIVE: To investigate the therapeutic effects of quercetin on early-stage inflammation in hypertriglyceridemia (HTG)-related acute pancreatitis (AP) both in vivo and in vitro, and its possible mechanism. METHODS: In vivo, rats were fed a high-fat diet to induce HTG, and AP was induced by intraperitoneal injection of cerulein (50 MUg/kg * 2). Quercetin (100, 150 and 200 mg/kg) was administered by intraperitoneal injection after AP induction. In vitro, rat exocrine acinar cells were preincubated with palmitic acid (PA, 0.1 mmol/L, 6 h) with quercetin (5, 10, 20 and 40 MUM) prior to a cholecystokinin analog CCK-8 (20pM). Injury of the pancreas was assessed by amylase secretion and pancreatic histological evaluation. Inflammation was estimated by measuring IL-1beta, IL-6, TNFalpha and NF-kB expression. Dynamic expression of IRE1alpha, sXBP1, C/EBPalpha and C/EBPbeta was monitored by real-time PCR, immunofluorescence (IF) and western blot (WB). RESULTS: Quercetin intervention reduced plasma amylase level (P < 0.001) in a dose-dependent manner, attenuated pancreatic histopathological damage (P < 0.05), and reduced the mRNA and protein expression of NF-kB, IL-1beta, IL-6, TNFalpha (P < 0.05) more significantly in HTG-related AP rats than in normal lipid AP rats. Quercetin also down-regulated gene and protein expression levels of IRE1alpha, sXBP1, C/EBPalpha and C/EBPbeta in a dose-dependent manner. CONCLUSIONS: Quercetin attenuates early-stage inflammation in HTG-related AP, probably by reducing IRE1alpha, sXBP1, C/EBPalpha and C/EBPbeta expression. PMID- 26873427 TI - Building a global teledermatology collaboration. AB - Skin disease is common in low-resource countries and is associated with significant morbidity. The disease burden is often heightened by lack of access to adequate diagnosis and treatment. Teledermatology is a growing healthcare delivery modality that allows access to subspecialty care at a distance. This article describes how a low-cost teledermatology program was launched through collaboration between the Medical College of Wisconsin and Hillside Healthcare International. Several factors are required for a teledermatology program to be successful, beginning with a partnership between two entities that targets a locally identified need and is mutually beneficial to invested partners. The program should utilize the expertise of each partner, be based on an agreed upon process with clearly defined objectives, and protect patient privacy. After a program is implemented, adaptation to address challenges and best meet the needs of all parties involved will allow for continued success and sustainability. This process can serve as a model for other programs desiring to establish similar teledermatology partnerships in an academic setting. PMID- 26873430 TI - Risk for malignancy in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs compared to the general population: A nationwide cohort study in Japan. AB - OBJECTIVES: To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population. METHODS: Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database. RESULTS: We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/10(5) PY (271.4-361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667-0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/10(5) PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809-7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients. CONCLUSIONS: Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended. PMID- 26873432 TI - In Vitro Gamete Differentiation from Pluripotent Stem Cells as a Promising Therapy for Infertility. AB - Generation of gametes derived in vitro from pluripotent stem cells holds promising prospects for future reproductive applications. Indeed, it provides information on molecular and cellular mechanisms underlying germ cell (GC) development and could offer a new potential treatment for infertility. Great progress has been made in derivation of gametes from embryonic stem cells, despite ethical issues. Induced pluripotent stem cells (iPSCs) technology allows the reprogramming of a differentiated somatic cell, possibly emanating from the patient, into a pluripotent state. With the emergence of iPSCs, several studies created primordial GC stage to mature gamete-like cells in vitro in mice and humans. Recent findings in GC derivation suggest that in mice, functional gametes can be generated in vitro. This strengthens the idea that it might be possible in the future to generate functional human sperm and oocytes from pluripotent stem cells in culture. PMID- 26873433 TI - An Unexpected Subdural Collection: Story of a Prostatic Metastasis. PMID- 26873431 TI - A comparison of the diagnostic accuracy of the AD8 and BCAT-SF in identifying dementia and mild cognitive impairment in long-term care residents. AB - We compared the accuracy of the Brief Cognitive Assessment Tool-Short Form (BCAT SF) and AD8 in identifying mild cognitive impairment (MCI) and dementia among long-term care residents. Psychometric analyses of 357 long-term care residents (n = 228, nursing home; n = 129, assisted living) in Maryland referred for neuropsychological evaluation evidenced robust internal consistency reliability and construct validity for the BCAT-SF. Furthermore, hierarchical logistic regression and receiver operating characteristic curve analyses demonstrated superior predictive validity for the BCAT-SF in identifying MCI and dementia relative to the AD8. In contrast, previously reported psychometric properties or cut scores for the AD8 could not be cross-validated in this long-term care sample. Based on these findings, the BCAT-SF appears to be a more reliable and valid screening instrument than the AD8 for rapidly identifying MCI and dementia in long-term care residents. PMID- 26873434 TI - Rare Case of Excessive Beta-Human Chorionic Gonadotropin Producing Intrascrotal Leiomyosarcoma: Diagnostic Pitfalls and Therapeutic Implications. PMID- 26873435 TI - Increased Expression of Tripartite Motif (TRIM) 47 Is a Negative Prognostic Predictor in Human Prostate Cancer. AB - BACKGROUND: Many prognostic biomarkers associated with androgen signaling have been proposed in PC. The role of tripartite motif (TRIM) proteins remains unclear in PC. We investigated TRIM protein 47 (TRIM47) expression levels in human prostate tissues. METHODS: We performed immunohistochemistry using original TRIM47 antibody in prostate tissues obtained by radical prostatectomy (n = 105). Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range, 0-8) were calculated as the sum of the proportion and intensity scores. TRIM47 expression levels were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Associations between the clinicopathologic features of the patients and their TRIM47 status were analyzed. RESULTS: Western blot analysis validated the specificity of the anti-TRIM47 antibody in 293T cells. TRIM47 expression levels were found to be significantly increased in PC compared to benign tissues by both immunohistochemistry (P < .0001) and qRT-PCR (P = .003). Additionally, advanced pathologic stage (>= T3b) was found to be associated with high TRIM47 IR scores (>= 4; P = .04). Furthermore, high TRIM47 IR scores were also significantly correlated with worse cancer-specific survival rates in multivariate regression analyses (hazard ratio, 6.82; P = .016). CONCLUSION: The results of the present study indicated differential TRIM47 expression levels in human prostate tissues compared to benign tissues. Because high levels of TRIM47 expression were found to be a strong prognostic factor in PC, TRIM47 may represent a novel therapeutic target. PMID- 26873436 TI - Brain Metastasis Responsive to Pazopanib in Renal Cell Carcinoma: A Case Report and Review of the Literature. PMID- 26873437 TI - Functional benefits of implants placed during ablative surgery: A 5-year prospective study on the prosthodontic rehabilitation of 56 edentulous oral cancer patients. AB - BACKGROUND: The timing of placement as well as the functional benefit of interforaminal implants in edentulous patients treated for oral cancer is unclear. METHODS: Fifty-six patients were recruited at 2 institutions. In 1 institution, interforaminal implants were placed during ablative surgery, the other institution used conventional prosthodontics with optional placement of implants postsurgery (postponed-placement). Masticatory performance, bite force, and subjective masticatory function were assessed before and 6 months, 1 year, and 5 years after surgery. RESULTS: Implant-retained overdentures (IODs) demonstrated the highest bite force and the least problems with solid food and food choice. Masticatory performance was equal for IODs and conventional dentures. After 5 years, IODs from patients in the during-ablative-surgery cohort tend to have higher bite force and masticatory performance than those from patients in the postponed-placement cohort. CONCLUSION: IODs produce the highest overall masticatory function. Implant placement during ablative surgery seems to be functionally beneficial. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2103 E2111, 2016. PMID- 26873438 TI - The Cultural Competence of Graduating Nursing Students. AB - PURPOSE: Cultural competence is an essential component in nursing. The purpose of this study was to evaluate the level of cultural competence of graduating nursing students, to identify associated background factors to cultural competence, and furthermore to establish whether teaching multicultural nursing was implemented in nursing education. DESIGN: A structured Cultural Competence Assessment Tool was used in a correlational design with a sample of 295 nursing students in southern Finland. FINDINGS AND CONCLUSIONS: The level of cultural competence was moderate, and the majority of students had studied multicultural nursing. Minority background (p = .001), frequency of interacting with different cultures (p = .002), linguistic skills (p = .002), and exchange studies (p = .024) were positively associated to higher cultural competence. IMPLICATIONS FOR PRACTICE: To improve cultural competence in students, nursing education should provide continuous opportunities for students to interact with different cultures, develop linguistic skills, and provide possibilities for internationalization both at home and abroad. PMID- 26873439 TI - Why some tumours trigger neovascularisation and others don't: the story thus far. AB - BACKGROUND: Angiogenesis is not essential for tumours to develop and expand, as cancer can also grow in a non-angiogenic fashion, but why this type of growth occurs is unknown. Surprisingly, our data from mRNA transcription profiling did not show any differences in the classical angiogenic pathways, but differences were observed in mitochondrial metabolic pathways, suggesting a key role for metabolic reprogramming. We then validated these results with mRNA profiling by investigating differential protein expression via immunohistochemistry in angiogenic and non-angiogenic non-small cell lung cancers (NSCLCs). METHODS: Immunohistochemical staining for 35 angiogenesis- and hypoxia-related biomarkers were performed on a collection of 194 angiogenic and 73 non-angiogenic NSCLCs arranged on tissue microarrays. Sequencing of P53 was performed with frozen tissue samples of NSCLC. RESULTS: The non-angiogenic tumours were distinguished from the angiogenic ones by having higher levels of proteins associated with ephrin pathways, mitochondria, cell biogenesis, and hypoxia-inducible factor 1 (HIF1) regulation by oxygen and transcription of HIF-controlled genes but lower levels of proteins involved in the stroma, cell-cell signaling and adhesion, integrins, and Delta-Notch and epidermal growth factor (EGF)-related signaling. However, proteins classically associated with angiogenesis were present in both types of tumours at very comparable levels. Cytoplasmic expression of P53 was strongly associated with non-angiogenic tumours. A pilot investigation showed that P53 mutations were observed in 32.0% of angiogenic cases but in 71.4% of non angiogenic tumours. CONCLUSIONS: Our observations thus far indicate that both angiogenic and non-angiogenic tumours experience hypoxia/HIF and vascular endothelial growth factor (VEGF) pathway protein expression in a comparable fashion. However, angiogenesis does not ensue in the non-angiogenic tumours. Surprisingly, metabolic reprogramming seems to distinguish these two types of neoplastic growth. On the basis of these results, we raise the hypothesis that in some, but not in all cases, initial tissue remodeling and/or inflammation could be one of the secondary steps necessary to trigger angiogenesis. In the non angiogenic tumours, in which neovascularisation fails to occur, HIF pathway activation could be the driving force toward metabolic reprogramming. PMID- 26873440 TI - The mythology of "spontaneous" human combustion. PMID- 26873442 TI - Fatal bronchial obstruction due to a tumor fragment originating from the contralateral lung during pneumonectomy. PMID- 26873441 TI - Into the wax: forensic and anthropological analysis of human hairs in Merovingian and Carolingian royal seals (France). PMID- 26873443 TI - Molecular processes in the streptokinase thrombolytic therapy. AB - The aim of this research is to evaluate the current streptokinase thrombolytic treatment and to identify or improve new techniques that will base new approaches with a higher efficiency in this area of expertise. In order to be as realistic as possible a new method was set up using magnetic vectorized nanoparticles streptokinase and human blood thrombus. The experimental data confirm the maximum 83% thrombus lyses whenever increase streptokinase concentration. It is very probable to happen because of the presence of high concentration of antiplasmin in the blood that neutralizes around half of the thrombolytic potential of the sanguine plasminogen. The experiment shows also that only free serum plasminogen are available for streptokinase action in order to generate plasmin. PMID- 26873445 TI - Heparanase Is Essential for the Development of Acute Experimental Glomerulonephritis. AB - Heparanase, a heparan sulfate (HS)--specific endoglucuronidase, mediates the onset of proteinuria and renal damage during experimental diabetic nephropathy. Glomerular heparanase expression is increased in most proteinuric diseases. Herein, we evaluated the role of heparanase in two models of experimental glomerulonephritis, being anti-glomerular basement membrane and lipopolysaccharide-induced glomerulonephritis, in wild-type and heparanase deficient mice. Induction of experimental glomerulonephritis led to an increased heparanase expression in wild-type mice, which was associated with a decreased glomerular expression of a highly sulfated HS domain, and albuminuria. Albuminuria was reduced in the heparanase-deficient mice in both models of experimental glomerulonephritis, which was accompanied by a better renal function and less renal damage. Notably, glomerular HS expression was preserved in the heparanase-deficient mice. Glomerular leukocyte and macrophage influx was reduced in the heparanase-deficient mice, which was accompanied by a reduced expression of both types 1 and 2 helper T-cell cytokines. In vitro, tumor necrosis factor alpha and lipopolysaccharide directly induced heparanase expression and increased transendothelial albumin passage. Our study shows that heparanase contributes to proteinuria and renal damage in experimental glomerulonephritis by decreasing glomerular HS expression, enhancing renal leukocyte and macrophage influx, and affecting the local cytokine milieu. PMID- 26873447 TI - Activation of the OVOL1-OVOL2 Axis in the Hair Bulb and in Pilomatricoma. AB - OVOL1 and OVOL2, ubiquitously conserved genes encoding C2H2 zinc finger transcription factors in mammals, control epithelial cell proliferation, and differentiation, including those in skin. OVOL1 and OVOL2 expression is coordinately mediated via the Wnt signaling pathway, and OVOL1 negatively regulates OVOL2 expression in a transcriptional manner. Our previous study of OVOL1 expression in human skin revealed that OVOL1 is preferentially expressed in the inner root sheath of the hair follicle. Therefore, we hypothesized that the OVOL1-OVOL2 axis is involved in normal and neoplastic follicular differentiation. Immunohistochemical analysis showed that OVOL1 and OVOL2 were strongly expressed in a mutually exclusive manner in the cytoplasm of inner root sheath cells and matrix cells, respectively, in normal follicles. OVOL2 was also expressed in pilomatricoma, with only partial expression of OVOL1. Cultured human keratinocytes expressed OVOL1 and OVOL2 on both the mRNA and protein levels. The expression of OVOL2 was higher in keratinocytes transfected with siRNA of OVOL1. Ketoconazole, a hair growth stimulant, up-regulated the expression of OVOL1 but did not affect OVOL2 expression. These results indicated that the OVOL1-OVOL2 axis may actively contribute to cell differentiation and proliferation in the hair bulb, suggesting that the OVOL1 and OVOL2 may be therapeutic targets of hair disorders, including alopecia, and play important roles in the tumorigenesis of pilomatricoma. PMID- 26873450 TI - Acromegaly presenting as cutis verticis gyrata. PMID- 26873444 TI - First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia. AB - As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our "First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop". PMID- 26873446 TI - New Molecular Insight into Mechanism of Evolution of Mammalian Synthetic Prions. AB - Previous studies established that transmissible prion diseases could be induced by in vitro-produced recombinant prion protein (PrP) fibrils with structures that are fundamentally different from that of authentic PrP scrapie isoform (PrP(Sc)). To explain evolution of synthetic prions, a new mechanism referred to as deformed templating was introduced. Here, we asked whether an increase in expression level of the cellular form of PrP (PrP(C)) speeds up the evolution of synthetic strains in vivo. We found that in transgenic mice that overexpress hamster PrP(C), PrP(C) overexpression accelerated recombinant PrP fibril-induced conversion of PrP(C) to the abnormal proteinase K-resistant state, referred to as atypical PrPres, which was the first product of PrP(C) misfolding in vivo. However, overexpression of PrP(C) did not facilitate the second step of synthetic strain evolution transition from atypical PrPres to PrP(Sc), which is attributed to the stochastic nature of rare deformed templating events. In addition, the potential of atypical PrPres to interfere with replication of a short-incubation time prion strain was investigated. Atypical PrPres was found to interfere strongly with replication of 263K in vitro; however, it did not delay prion disease in animals. The rate of deformed templating does not depend on the concentration of substrate and is hence more likely to be controlled by the intrinsic rate of conformational errors in templating alternative self-propagating states. PMID- 26873449 TI - Differentiating parts of Cinnamomum cassia using LC-qTOF-MS in conjunction with principal component analysis. AB - Cinnamon bark (Rou Gui in Chinese), cinnamon twig (Gui Zhi) and shaved cinnamon bark (Gui Sin) have been widely used as spices and in traditional Chinese medicine since ancient times. On-going issues related to quality and authenticity necessitate the development of analytical methods capable of providing an objective evaluation of samples. In this study, chemical fingerprints of cinnamon bark, cinnamon twigs and shaved cinnamon bark were established using liquid chromatography quadruple time-of-flight mass spectrometry in conjunction with principal component analysis (PCA). From 125 samples of cinnamon, we identified the following eight compounds and their the detection ratios: coumarin, cinnamaldehyde, cinnamyl alcohol, cinnamic acid, 2-hydroxycinnamaldehyde, 2 hydroxycinnamic acid, 2-methoxycinnamaldehyde and 4-methoxycinnamaldehyde. Of these, 4-methoxycinnamaldehyde presented the largest variations in detection ratio, making up 64.0, 97.4 and 50.0% in cinnamon bark, cinnamon twig, and shaved cinnamon bark, respectively. The quantities of cinnamyl alcohol, coumarin and cinnamaldehyde also varied between the three parts of the plant. Chemical fingerprints of the three cinnamon samples were established using principal component analysis, the results of which indicate that cinnamon bark and shaved cinnamon bark could be easily differentiated, despite a marked similarity in outward appearance. Cinnamon twig was also shown to depart from the other clusters. The proposed method provides a fast and efficient means of identifying cinnamon herbs for quality control purposes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26873451 TI - Acromegaly. AB - Acromegaly is a rare, chronic, progressive disease characterized by an excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. It is caused by a pituitary adenoma in the vast majority of cases. The clinical diagnosis, based on symptoms related to GH excess, is often delayed due to the insidious nature of the disease. Consequently, patients often have established systemic complications at diagnosis with increased morbidity and premature mortality. Serum IGF-1 measurement is recommended as the initial screen for patients with suspected acromegaly. The gold standard diagnostic test remains the oral glucose tolerance test with concomitant GH measurement. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor agonists and the GH receptor antagonist pegvisomant) and radiotherapy. A multidisciplinary approach is recommended with often a requirement for combined treatment modalities. With disease control, associated morbidity and mortality can be reduced. The recently published evidence-based guidelines by the Endocrine society addressed important clinical issues regarding the evaluation and management of acromegaly. This review discusses advances in our understanding of the pathophysiology of acromegaly, diagnosis of various forms of the disease and focuses on current treatment modalities, and on future pharmacological therapies for patients with acromegaly. PMID- 26873452 TI - A sad mood increases attention to unhealthy food images in women with food addiction. AB - Food addiction and emotional eating both influence eating and weight, but little is known of how negative mood affects the attentional processes that may contribute to food addiction. The purpose of this study was to compare attention to food images in adult women (N = 66) with versus without food addiction, before and after a sad mood induction (MI). Participants' eye fixations were tracked and recorded throughout 8-s presentations of displays with healthy food, unhealthy food, and non-food images. Food addiction was self-reported using the Yale Food Addiction Scale. The sad MI involved watching an 8-min video about a young child who passed away from cancer. It was predicted that: (1) participants in the food addiction group would attend to unhealthy food significantly more than participants in the control group, and (2) participants in the food addiction group would increase their attention to unhealthy food images following the sad MI, due to increased emotional reactivity and poorer emotional regulation. As predicted, the sad MI had a different effect for those with versus without food addiction: for participants with food addiction, attention to unhealthy images increased following the sad MI and attention to healthy images decreased, whereas for participants without food addiction the sad MI did not alter attention to food. These findings contribute to researchers' understanding of the cognitive factors underlying food addiction. PMID- 26873454 TI - Consumer consciousness on meat and the environment - Exploring differences. AB - Global environmental challenges require changes in both the production and the consumption of goods. In this paper we analyse how consumers perceive the high environmental burden of meat. We analysed consumer environmental consciousness, including problem awareness and a support to action dimensions, latter including perceived self-efficacy as well as solutions to problems. The solutions were positioned on a continuum from increasing the efficiency of production to discussing sufficiency levels in consumption practices (techno-optimism, local meat, organic meat and meat reduction, respectively). We used a statistically representative survey sample (n = 1890) from the population of Finland and cluster analysis to explore differences among consumers. The analysis revealed that most Finns seem to be rather unsure of the study topic. At the same time they tend to have a comparably high level of self-efficacy (55 per cent of respondents) and endorsement of particularly local meat solution type (55%), followed by organic meat (35%), meat reduction (25%) and techno-optimism (15%), though the neutral stand was the most common one across the data. We also identified six consumer groups that reveal not only a high number of Highly unsure consumers (40%), but also some Rather conscious (20%) and a relatively small number of Highly conscious (8%). In addition, there were also easily observable groups of Careless conscious (14%), Rather unsure (9%) and Resistant (8%). The results highlight the need for a multitude of political actions to guide meat consumption, as there are groups that may benefit from practical tools for making dietary changes as well as groups in need for more comprehensive selection of measures, including environmental information. PMID- 26873453 TI - Chocolate intake is associated with better cognitive function: The Maine-Syracuse Longitudinal Study. AB - Chocolate and cocoa flavanols have been associated with improvements in a range of health complaints dating from ancient times, and has established cardiovascular benefits. Less is known about the effects of chocolate on neurocognition and behaviour. The aim of this study was to investigate whether chocolate intake was associated with cognitive function, with adjustment for cardiovascular, lifestyle and dietary factors. Cross-sectional analyses were undertaken on 968 community-dwelling participants, aged 23-98 years, from the Maine-Syracuse Longitudinal Study (MSLS). Habitual chocolate intake was related to cognitive performance, measured with an extensive battery of neuropsychological tests. More frequent chocolate consumption was significantly associated with better performance on the Global Composite score, Visual-Spatial Memory and Organization, Working Memory, Scanning and Tracking, Abstract Reasoning, and the Mini-Mental State Examination. With the exception of Working Memory, these relations were not attenuated with statistical control for cardiovascular, lifestyle and dietary factors. Prospective analyses revealed no association between cognitive function and chocolate intake measured up to 18 years later. Further intervention trials and longitudinal studies are needed to explore relations between chocolate, cocoa flavanols and cognition, and the underlying causal mechanisms. PMID- 26873456 TI - Ischaemic stroke from a large mitral vegetation as clinical presentation of infective endocarditis. PMID- 26873455 TI - Knowledge and perceptions of asthma in Zambia: a cross-sectional survey. AB - BACKGROUND: Zambia is currently experiencing an epidemiological transition, from communicable to non-communicable diseases. The annual rate of physician-diagnosed asthma is estimated at 3 %. However, the general public's knowledge of asthma symptoms and signs, and their perception of asthma remain unknown. A survey was conducted aiming to determine knowledge and perceptions of asthma among Zambians. METHODS: Adults and adolescents attending four clinics in the capital, Lusaka, were surveyed using a standardized questionnaire from July 2011 to March 2012. RESULTS: Data from 1,540 participants (mean age 30.7 years, 65% female) were collected. Most patients (74%) were living in low-cost housing. One hundred and sixteen (7.6%) participants reported either a medical diagnosis of asthma or currently taking asthma medications. The most frequent asthma symptoms reported were wheezing (88%), and waking up at night with either shortness of breath (85%), chest tightness (85%), or cough (67%). Medications used to treat asthma were mostly oral short-acting beta-agonists (SABA) (59%), inhaled SABA (30.2%) and antibiotics (29.8%). Inhaled steroids were only used by 16.4% while less than 1% were on long-acting beta-agonists (LABA). Many misconceptions were identified among the entire surveyed population with only 54.7% believing hospitalisations are not preventable, 54.7% believing asthma symptoms can be prevented with the right medications and 37% believing inhalers are addictive. Nearly 60% thought that people with asthma cannot exercise or play hard. Significantly more individuals with asthma compared to those without thought tablets are better than inhalers for the treatment of asthma (46% vs 30%). CONCLUSIONS: We conclude that knowledge on asthma is poor in Zambia, where there remains many misconceptions on asthma and its management. PMID- 26873459 TI - Speckle tracking echo to assess transthyretin amyloidosis type: is it useful (or necessary)? PMID- 26873457 TI - Tricuspid regurgitation progression and regression in pulmonary arterial hypertension: implications for right ventricular and tricuspid valve apparatus geometry and patients outcome. AB - AIMS: The aim of this study was to determine the mechanism of tricuspid regurgitation (TR) progression in pulmonary arterial hypertension (PAH) and its effect on survival. METHODS AND RESULTS: We studied 88 patients with PAH and functional TR (mean pulmonary artery pressure 49 +/- 14 mmHg; 43% idiopathic PAH) who had serial echocardiograms. TR progression (n = 35) was defined as <=mild TR on Echo 1 and >=moderate TR on Echo 2. TR regression (n = 17) was defined as >=moderate TR on Echo 1 and <=mild TR on Echo 2. Stable TR (n = 36) was defined as <=mild TR on both echoes. TR progression was associated with an increase in pulmonary artery systolic pressure (PASP, 62 +/- 22-92 +/- 23 mmHg, P < 0.0001), right ventricular (RV) enlargement, mainly at mid-ventricular level, increased RV sphericity (6.1 +/- 1.7-6.9 +/- 1.8, P = 0.004), tricuspid annular (TA) dilatation (4.0 +/- 0.7-4.6 +/- 0.7 cm, P < 0.0001), and increased tricuspid valve (TV) tenting area (2.0 +/- 0.7-2.5 +/- 1.0 cm2, P = 0.0003). TR regression was associated with a reduction in PASP (84 +/- 15-55 +/- 18 mmHg, P < 0.0001), reverse RV remodelling with a reduction in RV sphericity (6.3 +/- 1.4-5.5 +/- 1.0, P = 0.02), and a reduction in TA size (4.1 +/- 0.7-3.6 +/- 0.7 cm, P = 0.02) and TV tenting (2.1 +/- 0.7-1.3 +/- 0.5 cm2, P = 0.0002). TR progression was associated with all-cause mortality (log-rank P = 0.0007). CONCLUSION: In PAH, TR progression was associated with worsening pulmonary hypertension and adverse RV and TV apparatus remodelling. TR progression is associated with poor outcome in PAH. PMID- 26873458 TI - Comparison of the standard and speckle tracking echocardiographic features of wild-type and mutated transthyretin cardiac amyloidoses. AB - AIMS: To compare cardiac function in patients with the two types of transthyretin (TTR)-related amyloidoses [wild-type (wt) and mutated (m) TTR amyloidoses (ATTR)] using standard and speckle tracking echocardiography (STE). METHODS AND RESULTS: Twenty-one consecutive patients with biopsy-proved ATTRwt were compared with 21 patients with ATTRm from the database, matched by age and left ventricular (LV) wall thickness (n = 135, ATTRm). All patients were examined using 2D echocardiography. Apical four- and two-chamber, and long-axis views and basal, mid, and apical short-axis views were used to examine LV longitudinal, circumferential, and radial strains. LV ejection fraction (EF), LV basal circumferential/radial strain, and mid-radial strain were significantly lower in patients with ATTRwt compared with patients with ATTRm. There was no significant difference between the two groups in the other parameters. In the receiver operating characteristic curve analysis, LVEF and LV basal mean radial strain were the best parameters for distinguishing between the two groups. CONCLUSION: Patients with ATTRwt are characterized by lower LVEF, LV basal, and LV mid-radial strains compared with patients with ATTRm. LVEF and LV radial strain are useful in distinguishing between ATTRwt and ATTRm when TTR has been proved in biopsy specimens. PMID- 26873460 TI - Strain echocardiography is related to fibrosis and ventricular arrhythmias in hypertrophic cardiomyopathy. AB - AIMS: Hypertrophic cardiomyopathy (HCM) patients are at risk of ventricular arrhythmias (VAs). We aimed to explore whether systolic function by strain echocardiography is related to VAs and to the extent of fibrosis by cardiac magnetic resonance imaging (CMR). METHODS AND RESULTS: We included 150 HCM patients and 50 healthy individuals. VAs were defined as non-sustained and sustained ventricular tachycardia and aborted cardiac arrest. Left ventricular function was assessed by ejection fraction (EF) and by global longitudinal strain (GLS) assessed by speckle tracking echocardiography. Mechanical dispersion was calculated as standard deviation (SD) of time from Q/R on ECG to peak longitudinal strain in 16 left ventricular segments. Late gadolinium enhancement (LGE) was assessed by CMR. HCM patients had similar EF (61 +/- 5% vs. 61 +/- 8%, P = 0.77), but worse GLS (-15.7 +/- 3.6% vs. -21.1 +/- 1.9%, P < 0.001) and more pronounced mechanical dispersion (64 +/- 22 vs. 36 +/- 13 ms, P < 0.001) compared with healthy individuals. VAs were documented in 37 (25%) HCM patients. Patients with VAs had worse GLS (-14.1 +/- 3.6% vs. -16.3 +/- 3.4%, P < 0.01), more pronounced mechanical dispersion (79 +/- 27 vs. 59 +/- 16 ms, P < 0.001), and higher %LGE (6.1 +/- 7.8% vs. 0.5 +/- 1.4%, P < 0.001) than patients without VAs. Mechanical dispersion correlated with %LGE (R = 0.52, P < 0.001) and was independently associated with VAs (OR 1.6, 95% CI 1.1-2.3, P = 0.02) and improved risk stratification for VAs. CONCLUSION: GLS, mechanical dispersion, and LGE were markers of VAs in HCM patients. Mechanical dispersion was a strong independent predictor of VAs and related to the extent of fibrosis. Strain echocardiography may improve risk stratification of VAs in HCM. PMID- 26873462 TI - Friedmanniella aerolata sp. nov., isolated from air. AB - A novel bacterium, strain 7515T-26T, was isolated from an air sample collected in Taean region, Republic of Korea. Cells were aerobic, Gram-stain-positive, non flagellated cocci, growing in the temperature, pH and NaCl ranges of 10-33 degrees C, pH 5.0-9.0 and 0-2 % (w/v). It shared high 16S rRNA gene sequence similarity with Friedmanniella lacustris EL-17AT (97.6 %), Friedmanniella lucida FA2T (96.9 %) and Friedmanniella luteola FA1T (96.9 %), showing high sequence similarities of 96.5-97.6 % with members of the genus Friedmanniella. Phylogenetic trees based on 16S rRNA gene sequences showed that strain 7515T-26T and members of the genus Friedmanniella formed a compact cluster separable from other genera. The isolate contained anteiso-C15 : 0, iso-C14 : 0 3-OH and iso-C15 : 0 as the major cellular fatty acids, and MK-9(H4) as the predominant isoprenoid quinone. Polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two unknown phospholipids and one unknown lipid, and the DNA G+C content was 73.1 mol%. The peptidoglycan type was A3gamma. It showed DNA DNA hybridization values of less than 70 % with F. lacustris EL-17AT. On the basis of the evidence from this polyphasic study, a novel species, Friedmanniella aerolata sp. nov., is proposed. The type strain is 7515T-26T ( = KACC 17306T = DSM 27139T). PMID- 26873463 TI - Topological data analysis: A promising big data exploration tool in biology, analytical chemistry and physical chemistry. AB - An important feature of experimental science is that data of various kinds is being produced at an unprecedented rate. This is mainly due to the development of new instrumental concepts and experimental methodologies. It is also clear that the nature of acquired data is significantly different. Indeed in every areas of science, data take the form of always bigger tables, where all but a few of the columns (i.e. variables) turn out to be irrelevant to the questions of interest, and further that we do not necessary know which coordinates are the interesting ones. Big data in our lab of biology, analytical chemistry or physical chemistry is a future that might be closer than any of us suppose. It is in this sense that new tools have to be developed in order to explore and valorize such data sets. Topological data analysis (TDA) is one of these. It was developed recently by topologists who discovered that topological concept could be useful for data analysis. The main objective of this paper is to answer the question why topology is well suited for the analysis of big data set in many areas and even more efficient than conventional data analysis methods. Raman analysis of single bacteria should be providing a good opportunity to demonstrate the potential of TDA for the exploration of various spectroscopic data sets considering different experimental conditions (with high noise level, with/without spectral preprocessing, with wavelength shift, with different spectral resolution, with missing data). PMID- 26873461 TI - Normal range and usefulness of right ventricular systolic strain to detect subtle right ventricular systolic abnormalities in patients with heart failure: a multicentre study. AB - AIMS: The aim of the present multicentre study was to analyse a large cohort of healthy subjects and patients with a common condition such as heart failure (HF) with the purpose of determining the normal range and the usefulness of right ventricular (RV) systolic strain to detect subtle RV systolic abnormalities using 2D speckle-tracking echocardiography. METHODS AND RESULTS: We analysed 238 healthy subjects and a cohort of 642 patients characterized by asymptomatic patients (n = 216) and patients with HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction (n = 218 and n = 208, respectively) prospectively included in 10 centres. The normal range of RV systolic strain analysing the healthy subjects was as follows: RV global strain -24.5 +/- 3.8 and RV free wall strain -28.5 +/- 4.8 (lowest expected value -17 and -19%, respectively). Concerning the ability of these myocardial parameters to detect subtle RV systolic abnormalities, RV global and free wall systolic strain were able to detect subtle RV longitudinal systolic abnormalities in a significant proportion of patients with HFrEF and to a lesser extent in HFpEF despite preserved tricuspid annular plane systolic excursion, tricuspid lateral annular peak systolic velocity by pulsed tissue Doppler imaging, and RV fractional area change. In addition, RV global and free wall systolic strain were significantly linked to the symptomatic status of the patients. CONCLUSIONS: The findings from this study provide important data regarding the normal range of RV global and free wall systolic strain and highlight the clinical relevance of these RV myocardial parameters to detect subtle RV systolic abnormalities in patients with HF. PMID- 26873464 TI - Immuno-PCR: An ultrasensitive immunoassay for biomolecular detection. AB - Techniques that combine nucleic acid amplification with an antibody-based assay can dramatically increase the sensitivity of conventional immunoassays. This review summarizes the methodology and applications of one such protein detection technique that has been used for the past 23 years-the immuno-polymerase chain reaction (usually referred to as immuno-PCR or IPCR). The key component of an immuno-PCR is a DNA-antibody conjugate that serves as a bridge to link the solid phase immunoreaction with nucleic acid amplification. The efficiency of immuno PCR enables a 10- to 10(9)-fold increase in detection sensitivity compared with that of ELISA. Advancements in immuno-PCR have included improvements of production of the DNA-antibody conjugate, assay formats, and readout methods. As an ultrasensitive protein assay, immuno-PCR has a broad range of applications in immunological research and clinical diagnostics. PMID- 26873465 TI - Determination of ferrous and total iron in refractory spinels. AB - Accurate and precise determination of the redox state of iron (Fe) in spinels presents a significant challenge due to their refractory nature. The resultant extreme conditions needed to obtain complete dissolution generally oxidize some of the Fe(II) initially present and thus prevent the use of colorimetric methods for Fe(II) measurements. To overcome this challenge we developed a hybrid oxidimetric/colorimetric approach, using Ag(I) as the oxidimetric reagent for determination of Fe(II) and 1,10-phenanthroline as the colorimetric reagent for determination of total Fe. This approach, which allows determination of Fe(II) and total Fe on the same sample, was tested on a series of four geochemical reference materials and then applied to the analysis of Fe(Ni) spinel crystals isolated from simulated high-level-waste (HLW) glass and of several reagent magnetites. Results for the reference materials were in excellent agreement with recommended values, with the exception of USGS BIR-1, for which higher Fe(II) values and lower total Fe values were obtained. The Fe(Ni) spinels showed Fe(II) values at the detection limit (ca. 0.03 wt% Fe) and total Fe values higher than obtained by ICP-AES analysis after decomposition by lithium metaborate/tetraborate fusion. For the magnetite samples, total Fe values were in agreement with reference results, but a wide range in Fe(II) values was obtained indicating various degrees of conversion to maghemite. Formal comparisons of accuracy and precision were made with 13 existing methods. Accuracy for Fe(II) and total Fe was at or near the top of the group. Precision varied with the parameter used to measure it but was generally in the middle to upper part of the group for Fe(II) while that for total Fe ranged from the bottom of the group to near the top. PMID- 26873466 TI - Quantitative fluorescence kinetic analysis of NADH and FAD in human plasma using three- and four-way calibration methods capable of providing the second-order advantage. AB - The metabolic coenzymes reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are the primary electron donor and acceptor respectively, participate in almost all biological metabolic pathways. This study develops a novel method for the quantitative kinetic analysis of the degradation reaction of NADH and the formation reaction of FAD in human plasma containing an uncalibrated interferent, by using three-way calibration based on multi-way fluorescence technique. In the three-way analysis, by using the calibration set in a static manner, we directly predicted the concentrations of both analytes in the mixture at any time after the start of their reactions, even in the presence of an uncalibrated spectral interferent and a varying background interferent. The satisfactory quantitative results indicate that the proposed method allows one to directly monitor the concentration of each analyte in the mixture as the function of time in real-time and nondestructively, instead of determining the concentration after the analytical separation. Thereafter, we fitted the first order rate law to their concentration data throughout their reactions. Additionally, a four-way calibration procedure is developed as an alternative for highly collinear systems. The results of the four-way analysis confirmed the results of the three-way analysis and revealed that both the degradation reaction of NADH and the formation reaction of FAD in human plasma fit the first-order rate law. The proposed methods could be expected to provide promising tools for simultaneous kinetic analysis of multiple reactions in complex systems in real time and nondestructively. PMID- 26873467 TI - Conductive polymeric ionic liquids for electroanalysis and solid-phase microextraction. AB - Three novel electropolymerizable thiophene-based ionic liquids (ILs) were synthesized and characterized as potential candidates for developing selective extraction media for chemical analysis. Electropolymerization of the bis[(trifluoromethyl)sulfonyl]imide ([NTf2](-)) analogs successfully produced uniform polymeric thin-films on macro- and microelectrode substrates from both vinyl and methylimidazolium IL monomer derivatives. The resultant conducting polymer IL (CPIL) films were characterized by electrochemical methods and found to exhibit attractive behavior towards anionic species while simultaneously providing an exclusion barrier toward cationic species. Thermogravimetric analysis of the thiophene-based IL monomers established a high thermal stability, particularly for the methylimidazolium IL, which was stable until temperatures above 350 degrees C. Subsequently, the methylimidazolium IL was polymerized on 125 MUm platinum wires and utilized for the first time as a sorbent coating for headspace solid-phase microextraction (HS-SPME). The sorbent coating was easily prepared in a reproducible manner, provided high thermal stability, and allowed for the gas chromatographic analysis of polar analytes. The normalized response of the poly[thioph-C6MIm][NTf2]-based sorbent coating exhibited higher extraction efficiency compared to an 85 MUm polyacrylate fiber and excellent fiber-to-fiber reproducibility. Therefore, the electropolymerizable thiophene-based ILs were found to be viable new materials for the preparation of sorbent coatings for HS SPME. PMID- 26873468 TI - Magnetic ionic liquid in stirring-assisted drop-breakup microextraction: Proof-of concept extraction of phenolic endocrine disrupters and acidic pharmaceuticals. AB - The use of magnetic ionic liquids (MILs) is in constant growth due to their switchable properties in the presence of an external magnetic field along with the outstanding properties of ionic liquids. In this study, a novel stirring assisted drop-breakup microextraction (SADBME) approach is put forward, based on the synthesis and utilization of methyltrioctylammonium tetrachloroferrate (N8 8,8,1[FeCl4]), as a MIL. The proposed procedure complies with the principles of the green chemistry, since it uses low volumes of easily synthesized ILs-based magnetic extracting phases avoiding the use of toxic solvents. To demonstrate its applicability, the proposed microextraction procedure is studied in conjunction with HPLC for the determination of selected phenols and acidic pharmaceuticals in aqueous matrices, taking into account the main experimental variables involved. The results obtained are accurate and highly reproducible, thus making it a good alternative approach for routine analysis of phenols and acidic pharmaceuticals. The low-cost approach is straightforward, environmentally safe and exhibits high enrichment factors and absolute extraction percentages and satisfactory recoveries. To the best of our knowledge, this is the first time that a MIL is used for analytical purposes in a practical, efficient and environmentally friendly drop-breakup microextraction approach for small molecules. PMID- 26873469 TI - Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction. AB - Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox((r)), rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 degrees C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocol. PMID- 26873470 TI - Implementing a two-layer feed-forward catalytic DNA circuit for enzyme-free and colorimetric detection of nucleic acids. AB - In the present study, a highly sensitive and specific bio-sensing platform for enzyme-free and colorimetric detection of nucleic acids has been developed. The biosensor is composed of two DNA nanostructures and two fuel strands that construct the foundation of a feed-forward catalytic DNA circuit. Upon binding the target strand to a specific DNA nanostructure, the circuit is run in order that at the end a hemin-binding aptamer, with the ability to convert a colorless substrate into a colored substance is released. Based on this strategy, 4 pM of the target DNA can be easily detected in serum samples by naked eyes after only a two-hour incubation with the circuit; meanwhile, if the incubation time is extended to 3 h, the biosensor can detect 1 pM of the target DNA. Besides the elevated sensitivity, the circuit can truly discriminate a spurious target containing one nucleotide mismatch with high specificity. Overall, the enzyme free catalytic DNA circuit can be used as a sensitive alternative method to enzyme-based biosensors for the specific and cost-effective detection of nucleic acids. PMID- 26873471 TI - Capillary hydrodynamic chromatography reveals temporal profiles of cell aggregates. AB - Microbial cells are known to form aggregates. Such aggregates can be found in various matrices; for example, functional drinks. Capillary hydrodynamic chromatography (HDC) enables separation of particles by size using nanoliter scale volumes of samples. Here we propose an approach based on HDC for characterisation of real samples containing aggregated and non-aggregated bacterial and fungal cells. Separation of cells and cell aggregates in HDC arises from the parabolic flow profile under laminar flow conditions. In the presented protocol, hydrodynamic separation is coupled with different on-line and off-line detectors (light absorption/scattering and microscopy). The method has successfully been applied in the monitoring of dynamic changes in the microbiome of probiotic drinks. Chromatographic profiles of yogurt and kefir samples obtained at different times during fermentation are in a good agreement with microscopic images. Moreover, thanks to the implementation of an area imaging detector, capillary HDC could be multiplexed and used to profile spatial gradients in cell suspensions, which arise in the course of sedimentation of cells and cell aggregates. This result shows compatibility of sedimentation analysis and capillary HDC. We believe that the approach may find applications in the profiling of functional foods and other matrices containing aggregated bioparticles. PMID- 26873473 TI - Factors influencing post-exercise plasma protein carbonyl concentration. AB - Exercise of sufficient intensity and duration can cause acute oxidative stress. Plasma protein carbonyl (PC) moieties are abundant, chemically stable, and easily detectable markers of oxidative stress that are widely used for the interpretation of exercise-induced changes in redox balance. Despite many studies reporting acute increases in plasma PC concentration in response to exercise, some studies, including those from our own laboratory have shown decreases. This review will discuss the differences between studies reporting increases, decreases, and no change in plasma PC concentration following exercise in humans; highlighting participant physiology (i.e. training status) and study design (i.e. intensity, duration, and novelty of the exercise bout) as the main factors driving the direction of the PC response to exercise. The role of the 20S proteasome system is proposed as a possible mechanism mediating the clearance of plasma PC following exercise. Resting and exercise-induced differences in plasma protein composition and balance between tissues are also discussed. We suggest that exercise may stimulate the clearance of plasma PC present at baseline, whereas simultaneously increasing reactive oxygen species production that facilitates the formation of new PC groups. The balance between these two processes likely explains why some studies have reported no change or even decreases in plasma PC level post-exercise when other biomarkers of oxidative stress (e.g. markers of lipid peroxidation) were elevated. Future studies should determine factors that influence the balance between PC clearance and formation following acute exercise. PMID- 26873472 TI - 3D printed titanium micro-bore columns containing polymer monoliths for reversed phase liquid chromatography. AB - The potential of 3D selective laser melting (SLM) technology to produce compact, temperature and pressure stable titanium alloy chromatographic columns is explored. A micro bore channel (0.9 mm I.D. * 600 mm long) was produced within a 5 * 30 * 30 mm titanium alloy (Ti-6Al-4V) cuboid, in form of a double handed spiral. A poly(butyl methacrylate-co-ethyleneglycoldimethacrylate) (BuMA-co-EDMA) monolithic stationary phase was thermally polymerised within the channel for application in reversed-phase high-performance liquid chromatography. The prepared monolithic column was applied to the liquid chromatographic separation of intact proteins and peptides. Peak capacities of 69-76 (for 6-8 proteins respectively) were observed during isothermal separation of proteins at 44 degrees C which were further increased to 73-77 using a thermal step gradient with programmed temperature from 60 degrees C to 35 degrees C using an in-house built direct-contact heater/cooler platform based upon matching sized Peltier thermoelectric modules. Rapid temperature gradients were possible due to direct contact between the planar metal column and the Peltier module, and the high thermal conductivity of the titanium column as compared to a similar stainless steel printed column. The separation of peptides released from a digestion of E.coli was also achieved in less than 35 min with ca. 40 distinguishable peaks at 210 nm. PMID- 26873475 TI - Extrapolating results from adult trials to children. PMID- 26873474 TI - Erratum to: 'Screen-and-treat program by point-of-care of Atopobium vaginae and Gardnerella vaginalis in preventing preterm birth (AuTop trial): study protocol for a randomized controlled trial'. PMID- 26873477 TI - Serum Sclerostin: Not Only a Matter of Measurement But Also of Meaning. PMID- 26873476 TI - Study of levodopa response in Parkinson's disease: Observations on rates of motor progression. AB - INTRODUCTION: It is important to understand how the rate of motor progression in PD relates to dopaminergic treatment. METHODS: The methods for this study comprised prospective defined off state measurements of the levodopa response at 3-year intervals over a mean 13.3-year period in 34 patients enrolled before treatment initiation. RESULTS: Despite worsening of on and off scores, the magnitude of the l-dopa short-duration response is maintained as the disease progresses. A linear mixed-effects regression analysis of off phase motor scores showed a yearly deterioration of 2.3% of the maximum disability score. Greater motor disability at the commencement of treatment was an independent predictor of faster progression. Demented patients had worse motor function than those without dementia (P = 0.02), and motor deficit appeared to accelerate toward the end of the disease course in patients who had died. CONCLUSIONS: These observations should inform clinical trial design for drugs with possible neuroprotective properties. PMID- 26873478 TI - Bone Mineral Density in Sjogren Syndrome Patients with and Without Distal Renal Tubular Acidosis. AB - Primary Sjogren's syndrome (pSS) can be complicated by distal renal tubular acidosis (dRTA), which may contribute to low bone mineral density (BMD). Our objective was to evaluate BMD in pSS patients with and without dRTA as compared with healthy controls. BMD of lumbar spine (LS) and femoral neck (FN) was measured in 54 pSS patients and 162 healthy age- and sex-matched controls by dual energy X-ray absorptiometry (DXA). dRTA was defined as inability to reach urinary pH <5.3 after an ammonium chloride (NH4Cl) test. LS- and FN-BMD were significantly higher in pSS patients compared with controls (1.18 +/- 0.21 g/cm(2) for patients vs. 1.10 +/- 0.18 g/cm(2) for controls, P = 0.008 and 0.9 +/ 0.16 g/cm(2) for patients vs. 0.85 +/- 0.13 g/cm(2) for controls, P = 0.009, respectively). After adjustment for BMI and smoking, the LS- and FN-BMD remained significantly higher. Patients with dRTA (N = 15) did not have a significantly different LS- and FN-BMD compared with those without dRTA (N = 39) after adjustment for BMI, age, and gender. Thirty-seven (69 %) pSS patients were using hydroxychloroquine (HCQ). Unexpectedly, pSS patients had a significantly higher LS- and FN-BMD compared with healthy controls. Patients with dRTA had similar BMD compared with patients without dRTA. We postulate that an explanation for the higher BMD in pSS patients may be the frequent use of HCQ. PMID- 26873479 TI - Editorial: The Elephant in the Room: Targeting Ras for Therapeutic Development. PMID- 26873480 TI - Pharmacists' knowledge and interest in developing counseling skills relating to oral contraceptives. AB - BACKGROUND: Possessing correct therapeutic information on oral contraceptives is an important prerequisite for the provision of sound advice to women who are using these products. OBJECTIVES: This study examines Egyptian pharmacists' knowledge of pharmacotherapeutic aspects of oral contraceptives as well as interest in developing skills in providing counseling on oral contraceptive pills. SETTING: Community pharmacies throughout Alexandria, Egypt. METHODS: A cross-sectional survey was self-administered by a random sample of community pharmacists in Alexandria, Egypt. Five multiple choice questions likely to arise when counseling women on oral contraceptives were constructed. Questions covered compatibility with breastfeeding, precautions, health risks and managing missed pills of oral contraceptives. Using ordered logistic regression, a model was estimated to predict pharmacists' interest in developing skills in providing counseling on oral contraceptives. MAIN OUTCOME MEASURE: Pharmacists' aggregate scores for knowledge questions and pharmacists' interest in developing skills in providing counseling on oral contraceptive pills. RESULTS: Of the 181 approached pharmacists, 92 % participated. Twenty one pharmacists (13 %) did not know the correct answer to any question, 122 (73 %) answered one-two correctly, 23 (14 %) answered three-four correctly. No pharmacist answered all five questions correctly. For pharmacists' interest in developing skills in providing counseling on oral contraceptives, the percentage values for answers were: not interested at all (10.2 %), slightly interested (27.0 %), somewhat interested (23.4 %), interested (30.0 %) and extremely interested (9.6 %). Pharmacists' interest in developing skills in providing counseling on oral contraceptives was significantly associated with the number of women who requested advice from the pharmacists on oral contraceptives (OR 1.54, CI 1.24-1.91). In terms of the learning method of preference, percentage values for answers were: attending a workshop (4 %), online course (18 %), publications distributed to pharmacy (44 %), other methods (1 %) and more than one method (23 %). Ten percent were not interested in developing their skills on oral contraceptives. CONCLUSION: This study identifies considerable gaps among community pharmacists' knowledge of oral contraceptives. It also shows variation in willingness and choice of learning strategies among pharmacists to develop their skills in providing counseling on oral contraceptives. PMID- 26873481 TI - Seeking to understand: using generic qualitative research to explore access to medicines and pharmacy services among resettled refugees. AB - Introduction There are challenges associated with selecting a qualitative research approach. In a field abundant with terminology and theories, it may be difficult for a pharmacist to know where and how to begin a qualitative research journey. The purpose of this paper is to provide insight into generic qualitative research and to describe the journey of data collection of a novice qualitative researcher in the quest to answer her research question: 'What are the barriers to accessing medicines and pharmacy services for resettled refugees in Queensland, Australia?' Methodology Generic qualitative research draws on the strengths of one or more qualitative approaches. The aim is to draw out participants' ideas about things that are 'outside themselves'; rather than focussing on their inner feelings the research seeks to understand a phenomenon, a process, or the perspectives of participants. Sampling is designed to obtain a broad range of opinions about events and experiences and data collection includes interviews, questionnaires or surveys; thematic analysis is often used to analyse data. When to use Generic qualitative research provides an opportunity to develop research designs that fit researchers' epistemological stance and discipline, with research choices, including methodology and methods, being informed by the research question. Limitations Generic qualitative research is one of many methodologies that may be used to answer a research question and there is a paucity of literature about how to do it well. There is also debate about its validity as a qualitative methodology. PMID- 26873482 TI - Drug safety: withdrawn medications are only part of the picture. AB - In a research article published in BMC Medicine, Onakpoya and colleagues provide a historical review of withdrawals of medications for safety reasons. However, withdrawn medications are only one part of the picture about how regulatory agencies manage drug risks. Moreover, medications introduced before the increased pre-marketing regulations and post-marketing monitoring systems instituted after the thalidomide tragedy have little relevance when considering the present drug safety picture because the circumstances under which they were introduced were completely different. To more fully understand drug safety management and regulatory agency actions, withdrawals should be evaluated within the setting and timeframe in which the medications are approved, which requires information about approvals and safety warnings. Studies are needed that provide a more comprehensive current picture of the identification and evaluation of drug safety risks as well as how regulatory agencies deal with them. Please see related research article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916 016-0553-2. PMID- 26873483 TI - Elevated serum apolipoprotein E is associated with metastasis and poor prognosis of non-small cell lung cancer. AB - Apolipoprotein E (ApoE) is a factor involved in Alzheimer's disease, which recently attracted great attention as an important protein related to tumorigenesis and metastasis. However, serum ApoE levels and its diagnosis and prognosis value in non-small cell lung cancer (NSCLC) patients are still unknown. In 196 NSCLC patients and 203 healthy controls, serum ApoE was measured by turbidimetric immunoassay. The associations of serum ApoE levels with the clinicopathological characteristics and clinical outcomes of NSCLC patients were analyzed. Serum ApoE levels were obviously elevated in NSCLC patients compared with healthy controls (41.6 +/- 11.63 vs. 33.8 +/- 6.24 mg/L) and were associated with TNM stage, lymph node metastasis status, and distant metastasis status (all P < 0.0001). For NSCLC diagnosis, the area under the receiver operating characteristic (ROC) curve was 0.71 at a specificity of 0.90 and sensitivity of 0.47. For lymph node metastasis predicting, the area under the ROC curve was 0.68 at a specificity of 0.56 and sensitivity of 0.73. From ROC/area under curve (AUC) analysis, we used 41.25 mg/L as the serum ApoE cut-off value, to divide NSCLC patients into two groups, the median survival was 11.0 weeks (95 % CI = 8.7 to 13.3) for patients in high serum ApoE group and 20.0 weeks (95 % CI = 15.0 to 25.0) in low serum ApoE group. Serum ApoE levels elevated in NSCLC patients, which also associated with TNM stages, lymph node metastasis, distant metastasis, and poor prognosis, suggest that serum ApoE may act as a useful clinical serological biomarkers for evaluating the progress of NSCLC. PMID- 26873484 TI - Overexpression of c-Myb is associated with suppression of distant metastases in colorectal carcinoma. AB - The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p < 0.01) but not tumor differentiation, tumor stage, lymph node involvement, vascular invasion, tumor localization, age, and gender of the patients. Although the c-Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases. PMID- 26873485 TI - The SMAD2/3 pathway is involved in hepaCAM-induced apoptosis by inhibiting the nuclear translocation of SMAD2/3 in bladder cancer cells. AB - The aim of this study was to explore the correlation between hepatocyte cell adhesion molecule (hepaCAM) and SMAD family member 2/3 (SMAD2/3) in bladder carcinoma, and the involvement of the SMAD2/3 pathway in hepaCAM-induced tumor apoptosis. Immunohistochemistry was used to measure hepaCAM and p-SMAD2/3 protein levels in bladder cancer tissues. Flow cytometry and Hoechst staining were used to study the effect of hepaCAM on cellular apoptosis. Western blot was employed to determine the expression of hepaCAM and SMAD2/3/caspase pathway molecules using a hepaCAM overexpression adenovirus, a caspase inhibitor (Z-VAD-FMK), and a SMAD2/3 activator (transforming growth factor (TGF)-beta1), respectively. Translocation of p-SMAD2/3 was measured by immunofluorescence and western blot. HepaCAM proteins were significantly decreased (P < 0.05), while p-SMAD2/3 proteins were remarkably increased (P < 0.05) in bladder carcinoma compared to adjacent tissues. However, the low hepaCAM and high p-SMAD2/3 were not statistically associated with clinicopathological characteristics of the patients. A negative linear correlation between hepaCAM and p-SMAD2/3 was observed according to Pearson analysis (r = -0.712/-0.724, P = 0.008/0.011). Overexpression of hepaCAM activated caspase 3/8/9 and downregulated poly-ADP ribose polymerase (PARP) and p-SMAD2/3. Treatment of bladder cancer cells with Z VAD-FMK + hepaCAM significantly downregulated procaspase 3/8/9 and PARP and induced cellular apoptosis, compared with that using Z-VAD-FMK alone. Similarly, combined treatment of TGF-beta1 + hepaCAM significantly downregulated p-SMAD2/3, procaspase 3/8/9, and PARP and induced apoptosis of bladder cancer cells, compared with TGF-beta1 alone. Overexpression of hepaCAM prevented the p-SMAD2/3 translocation from the cytoplasm to the nucleus in bladder cancer cells BIU-87 and T24. Our findings uncover that the p-SMAD2/3 pathway is critical for hepaCAM induced cancer cell apoptosis and provide valuable insights for current and future Ad-hepaCAM and p-SMAD2/3 clinical trials. PMID- 26873486 TI - Bone marrow stromal cells induced activation of nuclear factor kappaB signaling protects non-Hodgkin's B lymphoma cells from apoptosis. AB - The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-kappaB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-kappaB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis. PMID- 26873487 TI - Correlation of TGF-beta1 and oxidative stress in the blood of patients with melanoma: a clue to understanding melanoma progression? AB - TGF-beta1 and oxidative stress are involved in cancer progression, but in melanoma, their role is still controversial. Our aim was to correlate plasma TGF beta1 levels and systemic oxidative stress biomarkers in patients with melanoma, with or without disease metastasis, to understand their participation in melanoma progression. Thirty patients were recruited for melanoma surveillance, together with 30 healthy volunteers. Patients were divided into two groups: Non metastasis, comprising patients with tumor removal and no metastatic episode for 3 years; and Metastasis, comprising patients with a metastatic episode. The plasmatic cytokines TGF-beta1, IL-1 beta, and TNF-alpha were analyzed by ELISA. For oxidative stress, the following assays were performed: malondialdehyde (MDA), advanced oxidation protein products (AOPP) levels, total radical-trapping antioxidant parameter (TRAP) and thiol in plasma, and lipid peroxidation, SOD and catalase activity and GSH in erythrocytes. Patients with a metastatic episode had less circulating TGF-beta1 and increased TRAP, thiol, AOPP and lipid peroxidation levels. MDA was increased in both melanoma groups, while catalase, GSH, and IL 1beta was decreased in Non-metastasis patients. Significant negative correlations were observed between TGF-beta1 levels and systemic MDA, and TGF-beta1 levels and systemic AOPP, while a positive correlation was observed between TGF-beta1 levels and erythrocyte GSH. Lower levels of TGF-beta1 were related to increased oxidative stress in Metastasis patients, reinforcing new evidence that in melanoma TGF-beta1 acts as a tumor suppressor, inhibiting tumor relapse. These findings provide new knowledge concerning this cancer pathophysiology, extending the possibilities of investigating new therapies based on this evidence. PMID- 26873488 TI - Transforming growth factor (TGF) beta1 acted through miR-130b to increase integrin alpha5 to promote migration of colorectal cancer cells. AB - Transforming growth factor (TGF)-beta1 is a significant stimulator of tumor invasion and metastasis. More recently, it has been found that TGF-beta1 acts through microRNAs to regulate their target genes to promote cancer progresses. However, such similar regulation is rarely reported in colorectal cancer (CRC). Here, we observed a decrease in TGF-beta1 expression in CRC specimens, compared with matched adjacent normal tissues. In parallel, there was an increase in miR 130b characterized in the same samples by microarray assay. Further, treatment of CRC cells with TGF-beta1 caused a significant decrease in the expression of miR 130b and an increased CRC cell migration. Luciferase reporter assay revealed that miR-130b directly targeted the 3' untranslated region (3'UTR) region of integrin alpha5 gene, which encodes a key molecule involved in cell motility. Subsequently, in the overexpression of miR-130b CRC cells, we observed a decreased level of integrin alpha5 protein. The regulation of integrin alpha5 by miR-130b was further shown using the miR-130b mimics and inhibitor of miR-130b. And, knockdown miR-130b with inhibitor in the overexpression of miR-130b CRC cells recovered integrin alpha5 expression and integrin alpha5-mediated cell motility. Moreover, the inverse relevance between miR-130b and integrin alpha5 was also observed in CRC specimens. At last, the enhancement of integrin alpha5 in TGF-beta1-treated cells can be reversed partly when rescuing miR-130b expression. Together, our findings suggested that TGF-beta1 acted through miR 130b to promote integrin alpha5 expression, resulting in the enhanced migration of CRC cells. PMID- 26873489 TI - In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells. AB - Lung cancer is the most lethal cancer-related disease worldwide. Since survival rates remain poor, there is an urgent need for more effective therapies that could increase the overall survival of lung cancer patients. Lung tumors exhibit increased levels of oxidative markers with altered levels of antioxidant defenses, and previous studies demonstrated that the overexpression of the antioxidant enzyme catalase (CAT) might control tumor proliferation and aggressiveness. Herein, we evaluated the effect of CAT treatment on the sensitivity of A549 human lung adenocarcinoma cells toward various anticancer treatments, aiming to establish the best drug combination for further therapeutic management of this disease. Exponentially growing A549 cells were treated with CAT alone or in combination with chemotherapeutic drugs (cisplatin, 5 fluorouracil, paclitaxel, daunorubicin, and hydroxyurea). CalcuSyn((r)) software was used to assess CAT/drug interactions (synergism or antagonism). Growth inhibition, NFkappaB activation status, and redox parameters were also evaluated in CAT-treated A549 cells. CAT treatment caused a cytostatic effect, decreased NFkappaB activation, and modulated the redox parameters evaluated. CAT treatment exhibited a synergistic effect among most of the anticancer drugs tested, which is significantly correlated with an increased H2O2 production. Moreover, CAT combination caused an antagonism in paclitaxel anticancer effect. These data suggest that combining CAT (or CAT analogs) with traditional chemotherapeutic drugs, especially cisplatin, is a promising therapeutic strategy for the treatment of lung cancer. PMID- 26873490 TI - The potential role of CacyBP/SIP in tumorigenesis. AB - Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP) was initially described as a binding partner of S100A6 in the Ehrlich ascites tumor cells and later as a Siah-1-interacting protein. This 30 kDa protein includes three domains and is involved in cell proliferation, differentiation, cytoskeletal rearrangement, and transcriptional regulation via binding to various proteins. Studies have also shown that the CacyBP/SIP is a critical protein in tumorigenesis. But, its promotion or suppression of cancer progression may depend on the cell type. In this review, the biological characteristics and target proteins of CacyBP/SIP have been described. Moreover, the exact role of CacyBP/SIP in various cancers is discussed. PMID- 26873491 TI - What Time is it? Adherence to Antiretroviral Therapy in Ethiopia. AB - This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients' perspectives and identify effective interventions. PMID- 26873492 TI - HIV Risk Behavior Among Methamphetamine Users Entering Substance Abuse Treatment in Cape Town, South Africa. AB - South Africa is experiencing a growing methamphetamine problem, and there is concern that methamphetamine use may accelerate HIV transmission. There has been little research on the HIV prevention needs of methamphetamine users receiving substance abuse treatment in South Africa. This study assessed the prevalence and correlates of HIV risk behaviors among 269 methamphetamine users entering substance abuse treatment in two clinics in Cape Town. The prevalence of sexual risk behaviors was high among sexually active participants: 34 % multiple partners, 26 % unprotected intercourse with a casual partner, and 24 % sex trading for money/methamphetamine. The strongest predictor of all sexual risk behaviors was concurrent other drug use. Over half had not been HIV tested in the past year, and 25 % had never been tested, although attitudes toward HIV testing were overwhelmingly positive. This population of primarily heterosexual, non injecting methamphetamine users is a high-risk group in need of targeted HIV prevention interventions. Substance abuse treatment is an ideal setting in which to reach methamphetamine users for HIV services. PMID- 26873494 TI - Diffusion weighted imaging in cystic fibrosis disease: beyond morphological imaging. AB - OBJECTIVES: To explore the feasibility of diffusion-weighted imaging (DWI) to assess inflammatory lung changes in patients with Cystic Fibrosis (CF) METHODS: CF patients referred for their annual check-up had spirometry, chest-CT and MRI on the same day. MRI was performed in a 1.5 T scanner with BLADE and EPI-DWI sequences (b = 0-600 s/mm2). End-inspiratory and end-expiratory scans were acquired in multi-row scanners. DWI was scored with an established semi quantitative scoring system. DWI score was correlated to CT sub-scores for bronchiectasis (CF-CTBE), mucus (CF-CTmucus), total score (CF-CTtotal-score), FEV1, and BMI. T-test was used to assess differences between patients with and without DWI-hotspots. RESULTS: Thirty-three CF patients were enrolled (mean 21 years, range 6-51, 19 female). 4 % (SD 2.6, range 1.5-12.9) of total CF-CT alterations presented DWI-hotspots. DWI-hotspots coincided with mucus plugging (60 %), consolidation (30 %) and bronchiectasis (10 %). DWItotal-score correlated (all p < 0.0001) positively to CF-CTBE (r = 0.757), CF-CTmucus (r = 0.759) and CF CTtotal-score (r = 0.79); and negatively to FEV1 (r = 0.688). FEV1 was significantly higher (p < 0.0001) in patients without DWI-hotspots. CONCLUSIONS: DWI-hotspots strongly correlated with radiological and clinical parameters of lung disease severity. Future validation studies are needed to establish the exact nature of DWI-hotspots in CF patients. KEY POINTS: * DWI hotspots only partly overlapped structural abnormalities on morphological imaging * DWI strongly correlated with radiological and clinical indicators of CF-disease severity * Patients with more DWI hotspots had lower lung function values * Mucus score best predicted the presence of DWI-hotspots with restricted diffusion. PMID- 26873495 TI - Sacubitril/Valsartan: A Review in Chronic Heart Failure with Reduced Ejection Fraction. AB - Sacubitril/valsartan (EntrestoTM; LCZ696) is an orally administered supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was recently approved in the US and the EU for the treatment of chronic heart failure (NYHA class II IV) with reduced ejection fraction (HFrEF). In the large, randomized, double blind, PARADIGM-HF trial, sacubitril/valsartan reduced the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure (composite primary endpoint) significantly more than the angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan was also superior to enalapril in reducing death from any cause and in limiting the progression of heart failure. Sacubitril/valsartan was generally well tolerated, with no increase in life-threatening adverse events. Symptomatic hypotension was significantly more common with sacubitril/valsartan than with enalapril; the incidence of angio-oedema was low. Therefore, sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an ARB in the treatment of HFrEF, and is likely to influence the basic approach to treatment. PMID- 26873493 TI - Morphological imaging and T2 and T2* mapping of hip cartilage at 7 Tesla MRI under the influence of intravenous gadolinium. AB - OBJECTIVES: To investigate the influence of intravenous gadolinium on cartilage T2 and T2* relaxation times and on morphological image quality at 7-T hip MRI. METHODS: Hips of 11 healthy volunteers were examined at 7 T. Multi-echo sequences for T2 and T2* mapping, 3D T1 volumetric interpolated breath-hold examination (VIBE) and double-echo steady-state (DESS) sequences were acquired before and after intravenous application of gadolinium according to a delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol. Cartilage relaxation times were measured in both scans. Morphological sequences were assessed quantitatively using contrast ratios and qualitatively using a 4-point Likert scale. Student's t test, Pearson's correlation (rho) and Wilcoxon sign-rank test were used for statistical comparisons. RESULTS: Pre- and post-contrast T2 and T2* values were highly correlated (T2: acetabular: rho = 0.76, femoral: rho = 0.77; T2*: acetabular: rho = 0.80, femoral: rho = 0.72). Gadolinium enhanced contrasts between cartilage and joint fluid in DESS and T1 VIBE according to the qualitative (p = 0.01) and quantitative (p < 0.001) analysis. The delineation of acetabular and femoral cartilage and the labrum predominantly improved with gadolinium. CONCLUSIONS: Gadolinium showed no relevant influence on T2 or T2* relaxation times and improved morphological image quality at 7 T. Therefore, morphological and quantitative sequences including dGEMRIC can be conducted in a one-stop-shop examination. KEY POINTS: * Hip cartilage T2 values correlate highly before and after gadolinium at 7 T * Hip cartilage T2* values correlate highly before and after enhancement at 7 T * Morphological hip cartilage imaging benefits from intravenous gadolinium at 7 T * The delineation of acetabular and femoral cartilage can be improved by gadolinium * Morphological and quantitative sequences including dGEMRIC can be combined as a one-stop-shop examination. PMID- 26873497 TI - Investigation of endovenous laser ablation of varicose veins in vitro using 1.885 MUm laser radiation. AB - This paper presents the results of endovenous laser ablation (EVLA) of varicose veins in vitro using radiation of a solid-state laser based on the crystal LiYF4:Tm, with a wavelength of 1.885 MUm and power output of around 3 W. An experimental series with saline solution and red blood cell (RBC) suspension in the venous lumen was performed to identify the impact of a heated carbonized layer precipitated on the fiber end face versus the efficiency of EVLA. Results of these experiments confirmed that the presence of a heated carbonized layer on the fiber end face increases the efficiency of EVLA. PMID- 26873496 TI - Managing Metastatic Castration-Resistant Prostate Cancer in the Pre-chemotherapy Setting: A Changing Approach in the Era of New Targeted Agents. AB - In recent years, the therapeutic options for treating men with metastatic castration-resistant prostate cancer have increased substantially. The hormonal treatments abiraterone acetate and enzalutamide, the chemotherapeutics docetaxel and cabazitaxel, the radiopharmaceutical alpharadin and the immunotherapeutic Sipuleucel-T have entered the field. Additionally, corticosteroids, which are used extensively, have documented activity but no documented survival benefit. Physicians treating patients with metastatic prostate cancer immediately after castration resistance develops currently have at least four different options to choose from for the first treatment. These therapeutic choices and their several possible ways of sequential use have not yet been compared to each other head-to head and may never be. Therefore, there is an unmet need to inform their use with prospective clinical data. Additionally, the new indications of docetaxel for hormone naive prostate cancer is changing the landscape of prostate cancer treatment and questions the traditional classifications 'pre-chemotherapy' and 'post-chemotherapy'. In this work we attempt to address these challenges in the treatment of metastatic castration-resistant prostate cancer with the focus mainly on the non-cytotoxic agents. We try to integrate available clinical and preclinical information to suggest optimal ways of treatment. PMID- 26873498 TI - Effects of low-level laser therapy on performance, inflammatory markers, and muscle damage in young water polo athletes: a double-blind, randomized, placebo controlled study. AB - This study aimed to evaluate the effects of 5 days of 810-nm low-level laser therapy (LLLT) intervention on inflammatory and muscle damage markers and performance in young water polo players. Twenty young male water polo players participated in the study, which was designed as a randomized, double-blinded, placebo-controlled trial. Active LLLT or an identical placebo LLLT were delivered to eight points on the adductor muscle region immediately after each training day. Performance was measured by a 200-m maximal swimming (P200) and a 30-s crossbar jump test (30CJ) which was performed every day before training, and blood samples were drawn pre and post the final LLLT intervention to measure interleukins (IL) and muscle damage markers. There was no significant change in the P200 exercise in the LLLT group compared with the placebo group but there was a moderate improvement in the 30CJ (8.7 +/- 2.6 %). IL-1beta and tumor necrosis factor-alpha presented increased (P < 0.016) concentration within group 48 h after the last LLLT intervention compared to pre, 0, and 24 h, but did not differ between groups. IL-10 increased over time in the placebo group and reached a moderate effect compared to the LLLT group. The creatine kinase decreased significantly (P = 0.049) over the time within the LLLT treatment group, but there was no significant change in lactate dehydrogenase (P = 0.150). In conclusion, LLLT resulted in a non-significant, but small to moderate effect on inflammatory and muscle damage markers and a moderate effect on performance in water polo players. In addition, the lack of positive results could be due to the small area covered by irradiation and this should be considered in future studies. PMID- 26873499 TI - Synthesis of dental matrix proteins and viability of odontoblast-like cells irradiated with blue LED. AB - To evaluate the effect of irradiation with light-emitting diode (LED; 455 nm) on the viability and synthesis of dentin matrix proteins by odontoblast-like cells, MDPC-23 cells were cultivated (10(4) cells/cm(2)) in 24-well culture plates. After 12 h incubation in Dulbecco's modified Eagle's medium (DMEM), the cells were submitted to nutritional restriction by means of reducing the concentration of fetal bovine serum (FBS) for an additional 12 h. Cells were irradiated one single time with one of the following energy densities (EDs): 0.5, 2, 4, 10, or 15 J/cm(2) and irradiance fixed at 20 mW/cm(2). Non-irradiated cells served as control. After 72 h, cells were evaluated with regard to viability (methylthiazol tetrazolium technique (MTT)), mineralization nodule (MN) formation, total protein (TP) production, alkaline phosphatase activity (ALP), and collagen synthesis (Sircol), n = 8. The data were submitted to Kruskal-Wallis and Mann-Whitney tests (p > 0.05). There was no statistical difference between the viability of cells irradiated or not (control), for all the EDs. However, an increase in TP was observed for all the EDs when compared with the control group. A reduced ALP activity was seen in all irradiated groups, except for the ED of 0.5 J/cm(2), which did not differ from the control. There was no difference between the irradiated groups and control regarding collagen synthesis, with the exception of the ED of 10 J/cm(2), which inhibited this cell function. Significant reduction in MN occurred only for the EDs of 0.5 and 2 J/cm(2). The single irradiation with blue LED (455 nm), irradiance of 20 mW/cm(2), and energy densities ranging from 0.5 to 15 J/cm(2) exerted no effective biostimulatory capacity on odontoblast like cells. PMID- 26873500 TI - Light-emitting diode therapy increases collagen deposition during the repair process of skeletal muscle. AB - This study analyzed the effects of light-emitting diode (LED) therapy on the morphology of muscle tissue as well as collagen remodeling and matrix metalloproteinase 2 (MMP-2) activity in the skeletal muscle of rats following acute injury. Wistar rats were divided into four groups: (1) control, (2) sham, (3) untreated cryoinjury, and (4) cryoinjury treated with LED. Cryoinjury was induced by two applications of a metal probe cooled in liquid nitrogen directly onto the belly of the tibialis anterior muscle. For treatment, the LED equipment (wavelength 850 nm, output power 30 mW, and total energy 3.2 J) was used daily. The study periods were 1, 3, and 7 days after cryoinjury. Morphological aspects were evaluated through hematoxylin-eosin staining. The amount of collagen fibers was evaluated using Picro Sirius Red staining under polarized light. The gelatinase activity of MMP-2 was evaluated using zymography. The results showed significant reductions in inflammatory infiltrate after 3 days and an increased number of immature muscle fibers after 7 days. Furthermore, treatment induced a reduction in the gelatinolytic activity of MMP-2 after 1, 3, and 7 days in comparison to the untreated injury groups and increased the collagen deposition after 3 and 7 days in the treated groups. LED therapy at 850 nm induced a significant reduction in inflammation, decreased MMP-2 activity, and increased the amount of immature muscle and collagen fibers during the muscle repair process following acute injury. PMID- 26873501 TI - A randomized pilot study to assess the safety and the value of low-level laser therapy versus clonazepam in patients with burning mouth syndrome. AB - Comparison between low-level laser therapy (LLLT) and clonazepam for treating burning mouth syndrome (BMS) patients has never been documented; the aim of this study was to assess the effects of LLLT photobiomodulation versus medical therapy with clonazepam on BMS. Thirty-three patients (25 female, 8 male, mean age = 67.12) were randomly allocated to two different groups: the first one (group A, 18 patients) underwent two laser irradiation sessions weekly for 5 weeks, whereas the second one (group B, 15 patients) received topical clonazepam therapy [half a tablet (2 mg) in the mouth without swallowing for 3 min, three times a day for 21 days]. LLLT was delivered with a continuous wave 980-nm aluminum gallium arsenide (AlGaAs) diode laser and the output of 300 mW, delivering a Fluence of 10 J/cm(2), using a "spot technique," with an average power density of about 1 W/cm(2). The laser probe was held perpendicularly at a distance of about 2 mm from the mucosa. Visual analogue scale (VAS), McGill Pain Questionnaire, present pain intensity (PPI), and Oral Health Impact Profile (OHIP-49) assessed sensation of pain. Hospital Anxiety and Depression Scale and Geriatric Depression Scale assessed levels of anxiety and depression. Twelve weeks after the end of treatment, patients treated with LLLT experienced a decrease in pain sensation reported for all the parameters analyzed: VAS (P = 0.004), McGill Pain Questionnaire (P = 0.002), PPI (P = 0.002), and OHIP-49 (P = 0.010). The group treated with clonazepam had less favorable results for VAS (P = 0.33), McGill Pain Questionnaire (P = 0.005), PPI (P = 0.013), and OHIP-49 (P = 0.25). Levels of anxiety and depression did not change statistically in any groups (P > 0.05). Comparing the two groups, LLLT appeared to be superior in improving pain perception, but statistically only at 8 weeks after the end of the protocol proposed (P = 0.026). Based on this preliminary trial, LLLT is capable of reducing the symptoms of patients with BMS with a constant and long-lasting effect, experienced since the end of the first applications. PMID- 26873503 TI - GSK is fined L38m for delaying generic paroxetine. PMID- 26873502 TI - CO2 laser irradiation enhances CaF2 formation and inhibits lesion progression on demineralized dental enamel-in vitro study. AB - This study evaluated if Carbon dioxide (CO2) (lambda 10.6 MUm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances "CaF2" uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO2 laser irradiation (11.3 or 20.0 J/cm(2), 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as "CaF2 like material" formed on enamel was determined in 100 DES (n = 10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after "CaF2" extraction. In study 2, 165 DES (11 groups, n = 15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm(2) applied during APF gel application increased "CaF2" uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p < 0.05). Areas of melting, fusion, and cracks were observed. CO2 laser irradiation, combined with a single APF application enhanced "CaF2" uptake on enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF2 uptake by demineralized enamel and inhibited lesion progression. PMID- 26873504 TI - Serotype O:8 isolates in the Yersinia pseudotuberculosis complex have different O antigen gene clusters and produce various forms of rough LPS. AB - In Yersinia pseudotuberculosis complex, the O-antigen of LPS is used for the serological characterization of strains, and 21 serotypes have been identified to date. The O-antigen biosynthesis gene cluster and corresponding O-antigen structure have been described for 18, leaving O:8, O:13 and O:14 unresolved. In this study, two O:8 isolates were examined. The O-antigen gene cluster sequence of strain 151 was near identical to serotype O:4a, though a frame-shift mutation was found in ddhD, while No. 6 was different to 151 and carried the O:1b gene cluster. Structural analysis revealed that No. 6 produced a deeply truncated LPS, suggesting a mutation within the waaF gene. Both ddhD and waaF were cloned and expressed in 151 and No. 6 strains, respectively, and it appeared that expression of ddhD gene in strain 151 restored the O-antigen on LPS, while waaF in No. 6 resulted in an LPS truncated less severely but still without the O-antigen, suggesting that other mutations occurred in this strain. Thus, both O:8 isolates were found to be spontaneous O-antigen-negative mutants derived from other validated serotypes, and we propose to remove this serotype from the O-serotyping scheme, as the O:8 serological specificity is not based on the O-antigen. PMID- 26873505 TI - Differential regulation of aldose reductase expression during macrophage polarization depends on hyperglycemia. AB - Aldose reductase (AR; gene AKR1B1) is the rate-limiting enzyme of the polyol pathway and has been associated with diabetes and atherosclerosis. Here, we sought to identify the mechanisms underlying differential AR expression in human atherosclerotic plaque macrophages. In vitro, M1-polarized human monocyte-derived macrophages expressed significantly higher levels of AKR1B1 mRNA and AR protein compared with M2-polarized macrophages. AR activity was significantly higher in M1 macrophages. AKR1B1 mRNA expression correlated positively with the M1 marker TNF(r = 0.430,P = 0.006) and negatively with the M2 marker MRC1 (r = -0.443,P = 0.044). Increased AR expression in M1 macrophages depended on hyperglycemia. Concomitantly, expression of SLC2A1 (coding for the Glc transporter GLUT-1) was significantly higher in M1 than in M2 macrophages. Pharmacological inhibition of GLUT-1 using STF-32 completely abrogated Glc-induced AR up-regulation in M1 macrophages. When analyzing AR expression in post-mortem coronary artery plaque macrophages, a history of diabetes was associated with a significantly increased proportion of CD68(+)AR(++)macrophages, supporting the in vivo relevance of our in vitro findings. We demonstrate that the phenotype of atherosclerotic plaque macrophages may be affected by cardiovascular risk factors such as hyperglycemia. Our data illustrate the complex interplay between systemic and local factors in atherogenesis. PMID- 26873506 TI - Efinaconazole and Tavaborole. AB - PURPOSE: The purpose of this article is to review the safety, efficacy, and role of efinaconazole and tavaborole in the treatment of onychomycosis. SUMMARY: Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts, and nondermatophyte fungi. Distal and lateral subungual onychomycosis (DLSO) accounts for the majority of the cases. These infections cause structural damage to the nail which makes treatment difficult. Both oral and topical agents exist for the treatment of onychomycosis. Oral medications have generally been more effective, yet adverse effects and drug interactions limit their use in some patients. Food and Drug Administration (FDA)-approved agents in the United States for oral therapies include terbinafine, itraconazole, and griseofulvin. The only topical product available up to recently was ciclopirox. CONCLUSION: This article will review efinaconazole and tavaborole, 2 new topical antifungal agents released in 2014. PMID- 26873507 TI - Flibanserin. AB - OBJECTIVE: To review pivotal clinical trials, pharmacology, contraindications, precautions, and key patient education points of flibanserin for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. DATA SOURCES: A literature search of PubMed using the key words flibanserin and HSDD was conducted in September 2015. There was no time frame to exclude relevant clinical trials. All trials referenced were published between March 2012 and June 2014. Other relevant information was obtained from the Food and Drug Administration (FDA) Web site, press releases, prescribing information from the manufacturer, and ClinicalTrials.gov . STUDY SELECTION/DATA EXTRACTION: All articles in the English language and involving human subjects were reviewed. DATA SYNTHESIS: There are three 24-week, multicenter, randomized, double-blind, placebo controlled trials that evaluated the efficacy of flibanserin in North American premenopausal women with HSDD. There was 1 trial that studied the effects of flibanserin in postmenopausal women. In all of the trials, the investigators found statistical significant improvements in Female Sexual Function Index (FSFI) desire domain score and satisfying sexual events (SSEs). The most frequently reported adverse events in all flibanserin arms of treatment were somnolence, dizziness, and nausea. CONCLUSION: Flibanserin, a novel, nonhormonal agent that modulates excitatory and inhibitory neurotransmitters was studied in premenopausal women and has shown efficacy in improving sexual desire and SSEs. PMID- 26873509 TI - Analytical Similarity Assessment in Biosimilar Studies. AB - For assessment of biosimilarity, the US Food and Drug Administration (FDA) recommends a stepwise approach for obtaining the totality-of-the-evidence for demonstrating biosimilarity between a proposed biosimilar product and an innovative (reference) biological product. The stepwise approach starts with analytical studies for functional and structural characterization at various stages of manufacturing process of the proposed biosimilar product. Analytical similarity assessment involves identification of critical quality attributes (CQAs) that are relevant to clinical outcomes. FDA proposes first classifying the identified CQAs into three tiers according to their criticality or risking ranking relevant to clinical outcomes and then performing equivalence test (for CQAs in Tier 1), quality range approach (for CQAs in Tier 2), and raw data or graphical presentation (for CQAs in Tier 3) for obtaining totality-of-the evidence for demonstrating biosimilarity between the proposed biosimilar product with the reference product. In practice, some debatable issues are evitably raised due to this complicated process of analytical similarity assessment. In this article, these debatable are described and discussed. PMID- 26873508 TI - Mitochondrial network regulation and its potential interference with inflammatory signals in pancreatic beta cells. AB - Mitochondria fulfil multiple tasks in nutrient metabolism, energy production, redox homeostasis and stress response, and are essential for pancreatic beta cell function. The dynamism and health of the mitochondrial network is regulated by fission- and fusion-triggering factors and by a quality control system that removes dysfunctional organelles. Alongside the role of mitochondria in regulating apoptotic cell death mediated primarily via production of reactive oxygen species and release of cytochrome c, there is evidence of other links between mitochondria and inflammation that have implications for cell viability. This review briefly outlines two pathways that are potentially vital for pancreatic beta cell function. The first concerns the regulation of Parkin, a protein that acts, not only as a central player in regulating mitophagy, but also as an activator of the NF-KB pathway. The fact that expression of optic atrophy protein 1 (OPA1), a mitochondrial fusion inducer and master mitochondrial cristae biogenetic factor, is increased following NF-KB activation highlights a point of mitochondrial control that might be influenced by TNFalpha signalling. A second axis of interest is suggested by IL-6-mediated upregulation of the fission inducer FIS1 alongside downregulation of mitofusin 2 (MFN2), a guard of mitochondrial fusion and metabolism and an inhibitor of apoptosis. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied two other reviews on topics from this symposium (by Marc Donath, DOI: 10.1007/s00125-016 3873-z , and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ). PMID- 26873512 TI - Erratum. PMID- 26873510 TI - Sequential culture on biomimetic nanoclay scaffolds forms three-dimensional tumoroids. AB - In recent times, the limitation of two-dimensional cultures and complexity of in vivo models has paved the way for the development of three-dimensional models for studying cancer. Here we report the development of a new tumor model using PCL/HAPClay scaffolds seeded with a sequential culture of human mesenchymal stem cells (hMSCs) followed by human prostate cancer cells (HPCCs). This nanocomposite system is used as a test-bed for studying cancer metastasis and efficacy of anti cancer drugs using a polymersome delivery method. A novel sequential cell culture system in three-dimensional in vitro bone model provides a unique bone mimetic environment. The hMSCs seeded scaffolds are seeded with prostate cancer cells after the hMSCs have differentiated into osteoblasts. Sequential culture on the scaffolds has shown formation of tumoroids or microtissue consisting of organized, densely packed round cells with hypoxic core regions similar to in vivo tumors. Such tumoroids are not observed on HPCC seeded scaffolds or when HPCCs sequentially cultured with human osteoblast cells. Clearly, the newly differentiated hMSCs play a vital role in the ability of cancer cells to grow into tumoroids and cause disease. The PCL/HAPclay scaffold system seeded with the sequential culture of hMSCs, and HPCCs presents a good model system for study of the interactions between prostate cancer cells and bone microenvironment. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1591-1602, 2016. PMID- 26873511 TI - Between-Subject Variability in Healthy Eyes as a Primary Source of Structural Functional Discordance in Patients With Glaucoma. AB - PURPOSE: To test with an independent data set the finding that between-subject variability in healthy eyes is the primary source of structural-functional discordance in patients with glaucoma. METHODS: Neuroretinal rim area, retinal nerve fiber layer thickness, and perimetric data were analyzed for one eye in each of 55 control subjects and for 245 right eyes of patients in the United Kingdom Glaucoma Treatment Study. Data were gathered with the Heidelberg Retina Tomograph (HRT), Stratus Optical Coherence Tomograph (OCT), and Humphrey Field Analyzer (HFA). Discordance was quantified as width of the limits of agreement from a Bland-Altman analysis of depth of defect. The ratio of variances (F test) for the patient and control groups was computed for comparisons of HFA-OCT, HFA HRT, and OCT-HRT. Bonferroni adjustment required P less than 0.017 for statistical significance. The discordance in the patients was also quantified as the 95% prediction interval computed from the discordance in controls using the Hood-Kardon model for the HFA-OCT comparison. RESULTS: The F ratio comparing discordance in patients and controls was 0.77, 1.43, and 1.32 for the HFA-OCT, HFA-HRT, and OCT-HRT comparisons with P values 0.88, 0.06, and 0.11, respectively. For the Hood-Kardon model, 4.7% of the patients had discordance outside the 95% prediction interval computed from the discordance in controls. Similar results were obtained when all comparisons were repeated for left eyes of patients. CONCLUSIONS: These results confirm previous findings that between subject variability in healthy eyes is the primary source of structural functional discordance in patients with glaucoma, and extends this finding to a structural-structural comparison. PMID- 26873513 TI - How Eye Dominance Strength Modulates the Influence of a Distractor on Saccade Accuracy. AB - PURPOSE: Neuroimaging studies have shown that the dominant eye is linked preferentially to the ipsilateral primary visual cortex. However, its role in perception still is misunderstood. We examined the influence of eye dominance and eye dominance strength on saccadic parameters, contrasting stimulations presented in the two hemifields. METHODS: Participants with contrasted eye dominance (left or right) and eye dominance strength (strong or weak) were asked to make a saccade toward a target displayed at 5 degrees or 7 degrees left or right of a fixation cross. In some trials, a distractor at 3 degrees of eccentricity also was displayed either in the same hemifield as the target (to induce a global effect on saccade amplitude) or in the opposite hemifield (to induce a remote distractor effect on saccade latency). RESULTS: Eye dominance did influence saccade amplitude as participants with strong eye dominance showed more accurate saccades toward the target (weaker global effect) in the hemifield contralateral to the dominant eye than in the ipsilateral one. Such asymmetry was not found in participants with weak eye dominance or when a remote distractor was used. CONCLUSIONS: We show that eye dominance strength influences saccade target selection. We discuss several arguments supporting the view that such advantage may be linked to the relationship between the dominant eye and ipsilateral hemisphere. French Abstract. PMID- 26873514 TI - Glycerol Monolaurate Inhibits Lipase Production by Clinical Ocular Isolates Without Affecting Bacterial Cell Viability. AB - PURPOSE: We sought to determine the relative lipase production of a range of ocular bacterial isolates and to assess the efficacy of glycerol monolaurate (GML) in inhibiting this lipase production in high lipase-producing bacteria without affecting bacterial cell growth. METHODS: Staphylococcus aureus,Staphylococcus epidermidis,Propionibacterium acnes, and Corynebacterium spp. were inoculated at a density of 10(6)/mL in varying concentrations of GML up to 25 MUg/mL for 24 hours at 37 degrees C with constant shaking. Bacterial suspensions were centrifuged, bacterial cell density was determined, and production of bacterial lipase was quantified using a commercial lipase assay kit. RESULTS: Staphylococcus spp. produced high levels of lipase activity compared with P. acnes and Corynebacterium spp. GML inhibited lipase production by Staphylococcal spp. in a dose-dependent manner, with S. epidermidis lipase production consistently more sensitive to GML than S. aureus. Glycerol monolaurate showed significant (P < 0.05) lipase inhibition above concentrations of 15 MUg/mL in S. aureus and was not cytotoxic up to 25 MUg/mL. For S. epidermidis, GML showed significant (P < 0.05) lipase inhibition above 7.5 MUg/mL. CONCLUSIONS: Lipase activity varied between species and between strains. Staphylococcal spp. produced higher lipase activity compared with P. acnes and Corynebacterium spp. Glycerol monolaurate inhibited lipase production by S. aureus and S. epidermidis at concentrations that did not adversely affect bacterial cell growth. GML can be used to inhibit ocular bacterial lipase production without proving detrimental to commensal bacteria viability. PMID- 26873515 TI - Myopes Show Greater Visually Induced Postural Responses Than Emmetropes. AB - PURPOSE: The literature already establishes that vision plays a crucial role in postural control and that this visual dependence shows intra- and interindividual variability. However, does ametropia also have an effect on postural control? This question leads to our study, which aims primarily to determine if myopes and emmetropes behave differently in terms of postural control when subjected to visual stimulation, and secondarily, if this difference persists in the presence of barrel and pincushion distortions. The results could lead, among other things, to improved lens design. METHODS: Twenty-four subjects (12 myopes of -2.00 to 9.00 diopters [D] and 12 emmetropes of -0.50 to +0.50 D), between 19 and 35 years of age, participated in the study after comprehensive eye examinations were carried out. Of the 12 myopes, the preferred type of correction was divided equally within the group. While standing in front of a projection system and fixating on an immobile point, a checkerboard stimulus was displayed in their peripheral visual field, in either a static or dynamic state. Three conditions of optical distortion (plan, pincushion, and barrel distortions) were presented to the subjects. Their postural response was measured and recorded using a system of infrared cameras and optical sensors positioned on a helmet. RESULTS: The results show that postural instability induced by a dynamic peripheral stimulus is higher for myopes compared with emmetropes (ANOVA Refractive Error, F1,22 = 5.92, P = 0.0235). When exposed to optical distortions, the two groups also have significant differences in postural behaviors (ANOVA Refractive Error*Optical Distortion, F2,44 = 5.67, P = 0.0064). CONCLUSIONS: These results suggest that refractive error could be a factor in explaining individual variations of the role of vision in postural control. PMID- 26873516 TI - Correspondence IJC-D-16-00080. PMID- 26873517 TI - Chronic Obstructive Pulmonar Disease Mortality. SEPAR COPD-Smoking Year. PMID- 26873518 TI - Diagnosis and Treatment of Hemoptysis. AB - Hemoptysis is the expectoration of blood from the tracheobronchial tree. It is commonly caused by bronchiectasis, chronic bronchitis, and lung cancer. The expectorated blood usually originates from the bronchial arteries. When hemoptysis is suspected, it must be confirmed and classified according to severity, and the origin and cause of the bleeding determined. Lateral and AP chest X-ray is the first study, although a normal chest X-ray does not rule out the possibility of malignancy or other underlying pathology. Multidetector computed tomography (MDCT) must be performed in all patients with frank hemoptysis, hemoptoic sputum, suspicion of bronchiectasis or risk factors for lung cancer, and in those with signs of pathology on chest X-ray. MDCT angiography has replaced arteriography in identifying the arteries that are the source of bleeding. MDCT angiography is a non-invasive imaging technique that can pinpoint the presence, origin, number and course of the systemic thoracic (bronchial and non-bronchial) and pulmonary arterial sources of bleeding. Endovascular embolization is the safest and most effective method of managing bleeding in massive or recurrent hemoptysis. Embolization is indicated in all patients with life-threatening or recurrent hemoptysis in whom MDCT angiography shows artery disease. Flexible bronchoscopy plays a pivotal role in the diagnosis of hemoptysis in patients with hemoptoic sputum or frank hemoptysis. The procedure can be performed rapidly at the bedside (intensive care unit); it can be used for immediate control of bleeding, and is also effective in locating the source of the hemorrhage. Flexible bronchoscopy is the first-line procedure of choice in hemodynamically unstable patients with life-threatening hemoptysis, in whom control of bleeding is of vital importance. In these cases, surgery is associated with an extremely high mortality rate, and is currently only indicated when bleeding is secondary to surgery and its source can be accurately and reliably located. PMID- 26873520 TI - Clinical evaluation of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral lesions. AB - Percutaneous vertebral augmentation (Percutaneous vertebroplasty, PVP and Percutaeous kyphoplasty, PKP) for the treatment of metastatic spinal lesions has been considered as a preferred alternative to relieve pain and rebuild spinal stabilization relying on minimally invasive procedure. However, there have been few reports on clinical outcomes of percutaneous kyphoplasty in the treatment of osteolytic and osteoblastic metastatic vertebral fracture. We report our experience for 81 kyphoplasty procedures performed in 45 patients with thoracic and lumbar vertebral lesions caused by metastases. 4 out of the 45 patients were withdrawn at 1-year follow-up. 41 patients demonstrated good clinical result. The osteoblastic group performed a better pain relief in visual analog scale (VAS) score after the treatment than the osteoclastic group 3 days, 1 month, 3 months and 1 year after the KP. And the Oswestry Disability Index (ODI) scores of the osteoblastic group is lower than that of the osteoclastic group just in 3 days after the KP. And there were no significant difference between the two groups of ODI scores 1 month, 3 month and 1 year after the KP. And there were no statistical differences of the radiographic parameters including VB height variation and local kyphosis angle (LKA) between the two groups. Kyphoplasty results in an effective, minimally invasive procedure for the stabilization of thoracic and lumbar metastatic vertebral lesions, including both osteoblastic and osteoclastic types, which achieves statistically significant pain relief, function improvement, preventing further local kyphotic deformity, and VB height. PMID- 26873521 TI - The 100 most influential manuscripts in gastric cancer: A bibliometric analysis. AB - BACKGROUND: Bibliometric analysis highlights the key topics and publications which have shaped the understanding and management of Gastric cancer. Here the 100 most cited manuscripts in the field of gastric cancer (GC) are analysed. METHODS: The Thomson Reuters Web of Science database with the search terms 'gastric cancer' or 'gastric carcinoma' or 'stomach cancer' or 'stomach carcinoma' or 'gastroscopy' was used to identify all English language full manuscripts for the study. The 100 most cited papers were further analysed by topic, journal, author, year and institution. RESULTS: 122,616 eligible papers were returned and the median (range) citation number was 417 (2893-299). The most cited paper (by Parsonnet) focused on H.Pylori risk and gastric cancer (2893 citations). Cancer Research published the highest number of papers (n = 13, 6901 citations) and The New England Journal of Medicine (NEJM) had the most citations (n = 8, 9358 citations). The country and year with the greatest number of publications were the USA (n = 29), and 1998 (n = 10). The most ubiquitous topic was the pathology of gastric cancer (n = 57) followed by aetiology of gastric cancer (n = 47), and basic science of gastric cancer (n = 44). CONCLUSION: The most cited manuscripts highlighted in this study describe the science related to the pathogenesis of GC including surgery and regimens that have resulted in the contemporary understanding and treatment of GC. This work provides the most influential references related to GC and serves as a guide as to what makes a citable paper. PMID- 26873519 TI - ALE meta-analysis reveals dissociable networks for affective and discriminative aspects of touch. AB - Emotionally-laden tactile stimulation-such as a caress on the skin or the feel of velvet-may represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta-analysis was performed. This meta-analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n = 291, 34 experimental contrasts). A separate ALE meta-analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n = 1,075, 91 experimental contrasts). These meta-analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta-analytic connectivity (MCAM) analyses investigated network-level co-activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective-related PI and discriminative-related SI regions co-activated with different networks, implicated in dissociable functions, but sharing somatosensory co-activations. Taken together, these meta-analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct pathways. PMID- 26873522 TI - The NIK of time for B cells. AB - NF-kappaB-inducing kinase (NIK) is a key mediator of the noncanonical NF-kappaB signaling pathway, which is critical for B-cell development and function. Although complete deletion of NIK in mice has been shown to result in defective B cells and impaired secondary lymphoid organogenesis, the consequences of deleting NIK exclusively in B cells have not been determined. In this issue of the European Journal of Immunology, Hahn et al. [Eur. J. Immunol. 2016. 46: 732-741] describe mice in which the NF-kappaB2 pathway mediator, NIK, is deleted at different points in B-cell lineage differentiation and activation. The results show that the survival of mature peripheral B cells, as well as appropriate kinetics of germinal center reactions, rely on noncanonical NF-kappaB signaling. These findings confirm and extend prior observations implicating a nonredundant role for NF-kappaB2 downstream of BAFF signaling via BAFF-R, and prompt assessment of the growing literature regarding the relative roles of BCR and BAFF signals in B-cell homeostasis, as well as the downstream pathways responsible. PMID- 26873523 TI - Response to letter by Thodberg et al., AHB 2016. PMID- 26873524 TI - Infiltration of M2-polarized macrophages in infected lymphatic malformations: possible role in disease progression. AB - BACKGROUND: Lymphatic malformations (LMs), slow-flow vascular anomalies resulting from abnormal development of lymphatic channels, often progress rapidly after trauma or infection. OBJECTIVES: To explore the possible mechanism by which local infection promotes the progression of LMs. METHODS: Immunohistochemistry in serial sections and immunofluorescence were performed to label polarized macrophages. Tertiary lymphoid organs (TLOs) in LMs were identified using antibodies against CD3 (a T-cell marker), CD20 (a B-cell marker) and PNAd (a high endothelial venule marker). Pearson's correlation and cluster analysis were carried out to delineate the relationship between macrophage infiltration and TLO formation. Rat models of LM were established to examine the role of lipopolysaccharide in LM development. RESULTS: Compared with normal skin tissues, both M1- and M2-polarized macrophages were prevalent in LMs. Moreover, M2 polarized macrophages were significantly increased in infected LMs with an elevated density of TLOs. M2-polarized macrophages were observed in the centre of TLOs accompanied by intensive staining of macrophage colony-stimulating factor, a strong chemotactic factor for monocytes/macrophages, suggesting that macrophages might be recruited through TLOs. Cluster analysis and Pearson's correlation suggested a close relationship between macrophage infiltration and TLO formation. Furthermore, the expression of CD68 was also correlated with that of vascular endothelial growth factor (VEGF)-C and Ki67. Importantly, in an established LM rat model, lipopolysaccharide promoted the progression of the malformations with increased macrophage infiltration and TLO formation. CONCLUSIONS: M2-polarized macrophages that may be recruited through TLOs in infected LMs may contribute to the progression of the disease by secreting VEGF-C, and therefore accelerating the proliferation of lymphatic endothelial cells. PMID- 26873525 TI - Sensitivity of the cochlear nerve to acoustic and electrical stimulation months after a vestibular labyrinthectomy in guinea pigs. AB - Single-sided deafness patients are now being considered candidates to receive a cochlear implant. With this, many people who have undergone a unilateral vestibular labyrinthectomy for the treatment of chronic vertigo are now being considered for cochlear implantation. There is still some concern regarding the potential efficacy of cochlear implants in these patients, where factors such as cochlear fibrosis or nerve degeneration following unilateral vestibular labyrinthectomy may preclude their use. Here, we have performed a unilateral vestibular labyrinthectomy in normally hearing guinea pigs, and allowed them to recover for either 6 weeks, or 10 months, before assessing morphological and functional changes related to cochlear implantation. Light sheet fluorescence microscopy was used to assess gross morphology throughout the entire ear. Whole nerve responses to acoustic, vibrational, or electrical stimuli were used as functional measures. Mild cellular infiltration was observed at 6 weeks, and to a lesser extent at 10 months after labyrinthectomy. Following labyrinthectomy, cochlear sensitivity to high-frequency acoustic tone-bursts was reduced by 16 +/- 4 dB, vestibular sensitivity was almost entirely abolished, and electrical sensitivity was only mildly reduced. These results support recent clinical findings that patients who have received a vestibular labyrinthectomy may still benefit from a cochlear implant. PMID- 26873526 TI - The role of connectivity and stochastic osteocyte behavior in the distribution of perilabyrinthine bone degeneration. A Monte Carlo based simulation study. AB - Previous studies of undecalcified temporal bones labeled with fluorescent tissue time markers and basic fuchsine have documented the unique spatial and temporal patterns underlying inner ear bone development, morphology and degeneration, and has led to the identification of inner ear OPG as the candidate inhibiter of perilabyrinthine bone resorption. Resulting age related excessive matrix microdamage, osteocyte death and degeneration of the OPG signaling pathway is expected to trigger bone remodeling in the otic capsule, but when this happens the morphology of the remodeling bone is abnormal and the distribution is not entirely smooth and predictable, but rather multifocal and chaotic with a centripetal predilection at the window regions, as in otosclerosis. Based on the observed histological patterns, the fundamental preconditions of perilabyrinthine bone cell behavior can be deduced. When this information is used to generate a virtual computer representation of the cellular signaling network, the fate of the aging network can be studied by 'virtual histology' in any number of simulated 'individuals'. We demonstrate how a combination of simple osteocyte survival functions derived from histological observations and the effect of connectivity may account for gradual centripetal degeneration as well as occasional focal degeneration of the cellular anti resorptive signaling pathway around the fluid space of the inner ear and create a permissive environment for otosclerosis. PMID- 26873527 TI - [Evaluation and improvement of the comprehension of informed consent documents]. AB - INTRODUCTION: The information contained in a good informed consent form (ICF) must be understood by the patients. The aim of this study is to assess and improve the readability of the ICF submitted for accreditation in a tertiary hospital. METHODS: Study of assessment and improvement of the quality of 132 ICF from 2 departments of a public tertiary hospital, divided into 3 phases: Initial assessment, intervention and reassessment. Both length and readability are assessed. Length is measured in words (adequate to 470, excessive over 940), and readability in INFLESZ points (suitable if over 55). The ICF contents initially proposed by departments were adapted by non-health-related trained persons, whose doubts about medical terms were resolved by the authors. To compare results between evaluations, relative improvement (in both length and INFLESZ) and statistical significances were calculated. RESULTS: BASELINE DATA: 78.8% of the ICFs showed a desired length (CI95% 86,5-71,1) and a mean of 44.1 INFLESZ points (3.8% >55 points, CI95% 6,0-1,6). After the intervention, INFLESZ raised to 61.9 points (improvement 40.3%, P<.001), all ICF showing >55 points. The resulting ICFs had a longer description of the nature of the procedure (P<.0001) and a shorter description of their consequences, risks (P <.0001) and alternatives (P <.05). CONCLUSIONS: The introduction of improvement dynamics in the design of ICFs is possible and necessary because it produces more effective and easily readable ICFs. PMID- 26873528 TI - Elevated TNF-alpha is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. AB - BACKGROUND: Children and adults with the lysosomal storage diseases mucopolysaccharidosis (MPS) types I, II and VI live shortened lives permeated by chronic pain and physical disability. Current treatments do not alleviate these problems. Thus there is a critical need to understand the mechanism of chronic pain and disability in MPS in order to improve the way we treat patients. A potential target is inflammation. HYPOTHESIS: We hypothesized that excessive inflammation mediated by the tumor necrosis factor-alpha (TNF-alpha) inflammatory pathway is the fundamental cause of much of the chronic pain and physical disability in MPS. METHODS: 55 patients with MPS I, II, or VI were enrolled over the course of a 5-year prospective longitudinal natural history study and evaluated annually for 2-5years. 51 healthy controls were enrolled in a separate cross-sectional study of bone and energy metabolism. TNF-alpha was measured by ELISA. Pain and physical disability were measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50). Differences in log-transformed TNF alpha levels and associations with CHQ domains were evaluated using a linear mixed effects model with random intercept. RESULTS: TNF-alpha levels were measured in 48 MPS (age: 5-17years; 35% female) and 51 controls (age: 8-17years; 53% female). Among MPS, 22 (46%) were treated with hematopoietic cell transplantation (HCT) alone, 24 (50%) with enzyme replacement therapy (ERT) alone, and 2 (4%) with both HCT and ERT. TNF-alpha levels are higher in MPS compared to healthy controls (p<0.001). Higher TNF-alpha levels are associated with increased pain and decreased physical function, social limitations due to physical health, and physical summary score (all p<0.05). TNF-alpha levels were not significantly associated with the general health score. TNF-alpha levels did not change significantly over time in MPS. CONCLUSIONS: Higher TNF-alpha levels are implicated in the pain and decreased physical function present in individuals with MPS despite treatment with ERT and/or HCT, suggesting that TNF-a inhibition could potentially be a useful adjunctive therapy. Further investigation into the role of TNF-alpha inhibition in MPS to decrease pain and improve physical function is indicated. PMID- 26873529 TI - Observational clinical study of 22 adult-onset Pompe disease patients undergoing enzyme replacement therapy over 5years. AB - Pompe disease is an autosomal recessive disease resulting from deficiency of the acid alpha-glucosidase (GAA). The late-onset Pompe Disease (LOPD) patients develop muscular and respiratory complications later in life. We describe a retrospective observational cohort study including 22 patients with LOPD. The cohort was assessed at baseline before Enzyme Replacement Therapy (ERT) with alglucosidase alpha (20mg/kg biweekly) was commenced and subsequently relevant information was collected at 2, 4 and 5years later. The median age of the patients at study entry was 44years (16-64years), with median disease duration of 11.5years (4-31years). At baseline, 10 patients (45%) could walk without support, 12 (55%) could walk with unilateral or bilateral support including 3/12 were wheelchair bound. Mean predicted FVC % was 55.7 (95% CI 45-66) of predicted normal at baseline and showed no significant change after 5years (54.6 (95% CI 43 66)), (all p=0.9815). Mean FVC % supine was 41.8 (95% CI 33.8-49) of predicted normal at baseline and remained significantly unchanged at 5years (48.4 (95% CI 37-59.6)), (all p=0.8680). The overnight non-invasive ventilator dependence increased by 18.2% as compared with baseline and requirement of mobility aids increased during this period by 5.2% as compared with the baseline. Mean walking distance at 6min walk test was 411.5 (95% CI 338-485) at baseline, 266.5 (95% CI 187-346) m at 2years, 238.6 (95% CI 162-315) m at 4years and 286.8 (95% CI 203 370) m at 5years (p=0.1981; ANOVA was completed only for 14 patients). A gradual decline in FVC% predicted was noted only in four cases and a decline in FVC% supine in two other. Only one patient showed a decline in both pulmonary function tests. In all remaining cases (17/22) respiratory function remains stable. In conclusion overall pulmonary function tests and mobility remained stable for 5years in majority of patients on ERT. However, in some patients they continued to decline in spite of ERT resulting in increased number of patients requiring ventilation and increase wheel chair dependence at the end of 5years. PMID- 26873531 TI - Innovative pure non-exposed endoscopic full-thickness resection using an endoscopic suturing device. PMID- 26873532 TI - Interaction of graphene oxide with albumins: Effect of size, pH, and temperature. AB - Understanding the interaction between graphene oxide (GO) and the biomolecules is fundamentally essential, especially for disease- and drug-related peptides and proteins. In this study, the interaction between GO and albumins (bovine serum albumin, human serum albumin, and bovine alpha-lactalbumin) has been performed by fluorescence and UV-Vis spectroscopic techniques. The fluorescence quenching mechanism between GO and aromatic acids residues with intrinsic fluorescence was determined as mainly static quenching in combination with dynamic quenching. The optimal conditions for the most effective affinity between albumins and GO have been estimated at neutral pH and room temperature. The strong impact of the size of graphene oxide on the interaction between proteins and graphene oxide has been confirmed, as well. The interaction between GO and albumins has been examined as electrostatic and hydrophobic. The electrostatic interaction was confirmed by pH effect, while the hydrophobic interaction was proved by the presence of Poloxamer188. The CD spectra of albumins exhibit decreasing helicity in the secondary structure of albumins upon the addition of GO. However, no significant changes in position and shape of characteristic negative bands have been noted. Mentioned changes indicate the successful interaction between GO and proteins, the predominantly alpha-helical structure of albumins has been preserved. PMID- 26873533 TI - Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFalpha-activated endothelial cells at physiologically relevant concentrations. AB - An increasing number of evidence suggests a protective role of dietary anthocyanins against cardiovascular diseases. Anthocyanins' extensive metabolism indicates that their metabolites could be responsible for the protective effects associated with consumption of anthocyanin-rich foods. The aim of this work was to investigate the effect of plasma anthocyanins and their metabolites on the adhesion of monocytes to TNFalpha-activated endothelial cells and on the expression of genes encoding cell adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were exposed to circulating anthocyanins: cyanidin-3 arabinoside, cyanidin-3-galactoside, cyanidin-3-glucoside, delphinidin-3 glucoside, peonidin-3-glucoside, anthocyanin degradation product: 4 hydroxybenzaldehyde, or to their gut metabolites: protocatechuic, vanillic, ferulic and hippuric acid, at physiologically-relevant concentrations (0.1-2 MUM) and time of exposure. Both anthocyanins and gut metabolites decreased the adhesion of monocytes to HUVECs, with a magnitude ranging from 18.1% to 47%. The mixture of anthocyanins and that of gut metabolites also reduced monocyte adhesion. However, no significant effect on the expression of genes encoding E selectin, ICAM1 and VCAM1 was observed, suggesting that other molecular targets are involved in the observed effect. In conclusion, this study showed the potency of anthocyanins and their gut metabolites to modulate the adhesion of monocytes to endothelial cells, the initial step in atherosclerosis development, under physiologically-relevant conditions. PMID- 26873530 TI - EUS Needle Identification Comparison and Evaluation study (with videos). AB - BACKGROUND AND AIMS: EUS-guided FNA or biopsy sampling is widely practiced. Optimal sonographic visualization of the needle is critical for image-guided interventions. Of the several commercially available needles, bench-top testing and direct comparison of these needles have not been done to reveal their inherent echogenicity. The aims are to provide bench-top data that can be used to guide clinical applications and to promote future device research and development. METHODS: Descriptive bench-top testing and comparison of 8 commonly used EUS-FNA needles (all size 22 gauge): SonoTip Pro Control (Medi-Globe); Expect Slimline (Boston Scientific); EchoTip, EchoTip Ultra, EchoTip ProCore High Definition (Cook Medical); ClearView (Conmed); EZ Shot 2 (Olympus); and BNX (Beacon Endoscopic), and 2 new prototype needles, SonoCoat (Medi-Globe), coated by echogenic polymers made by Encapson. Blinded evaluation of standardized and unedited videos by 43 EUS endoscopists and 17 radiologists specialized in GI US examination who were unfamiliar with EUS needle devices. RESULTS: There was no significant difference in the ratings and rankings of these needles between endosonographers and radiologists. Overall, 1 prototype needle was rated as the best, ranking 10% to 40% higher than all other needles (P < .01). Among the commercially available needles, the EchoTip Ultra needle and the ClearView needle were top choices. The EZ Shot 2 needle was ranked statistically lower than other needles (30%-75% worse, P < .001). CONCLUSIONS: All FNA needles have their inherent and different echogenicities, and these differences are similarly recognized by EUS endoscopists and radiologists. Needles with polymeric coating from the entire shaft to the needle tip may offer better echogenicity. PMID- 26873534 TI - Development, CAPTA Part C Referral and Services Among Young Children in the U.S. Child Welfare System: Implications for Latino Children. AB - Amendments made to the Child Abuse Prevention and Treatment Act in 2003 and the Individuals with Disabilities Education Improvement Act in 2004 opened the door to a promising partnership between child welfare services and early intervention (EI) agencies by requiring a referral to EI services for all children under age 3 involved in a substantiated case of child abuse, neglect, or illegal drug exposure. However, little research has been conducted to assess the implications of these policies. Using data drawn from a nationally representative study conducted in 2008-2009, we observed less than a fifth of all children in substantiated cases to receive a referral to developmental services (18.2%) approximately 5 years after the passage of the amendments. Of children in contact with the U.S. child welfare system, Hispanic children of immigrants demonstrated the greatest developmental need yet were among the least likely to receive EI services by the end of the study period. Implications for policy and practice are discussed. PMID- 26873535 TI - Introduction to a New Section: "DDS-GRG Mentored Reviews". PMID- 26873536 TI - Continuing Medical Education Improves Gastroenterologists' Compliance with Inflammatory Bowel Disease Quality Measures. AB - BACKGROUND: Low rates of compliance with quality measures for inflammatory bowel disease (IBD) have been reported for US gastroenterologists. AIMS: We assessed the influence of quality improvement (QI) education on compliance with physician quality reporting system (PQRS) measures for IBD and measures related to National Quality Strategy (NQS) priorities. METHODS: Forty community-based gastroenterologists participated in the QI study; 20 were assigned to educational intervention and control groups, respectively. At baseline, randomly selected charts of patients with moderate-to-severe ulcerative colitis were retrospectively reviewed for the gastroenterologists' performance of 8 PQRS IBD measures and 4 NQS-related measures. The intervention group participated in a series of accredited continuing medical education (CME) activities focusing on QI. Follow-up chart reviews were conducted 6 months after the CME activities. Independent t tests were conducted to compare between-group differences in baseline-to-follow-up rates of documented compliance with each measure. RESULTS: The analysis included 299 baseline charts and 300 follow-up charts. The intervention group had significantly greater magnitudes of improvement than the control group for the following measures: assessment of IBD type, location, and activity (+14 %, p = 0.009); influenza vaccination (+13 %, p = 0.025); pneumococcal vaccination (+20 %, p = 0.003); testing for latent tuberculosis before anti-TNF-alpha therapy (+10 %, p = 0.028); assessment of hepatitis B virus status before anti-TNF-alpha therapy (+9 %, p = 0.010); assessment of side effects (+17 %, p = 0.048), and counseling patients about cancer risks (+13 %, p = 0.013). CONCLUSIONS: QI-focused CME improves community-based gastroenterologists' compliance with IBD quality measures and measures aligned with NQS priorities. PMID- 26873537 TI - Efficacy and Safety of Therapeutic Endoscopic Retrograde Cholangiopancreatography in the Elderly Over 80 Years. AB - BACKGROUND/AIMS: Concern regarding the safety and efficacy of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in elderly patients is increasing as a result of the aging society. However, there are limited data, especially in the super-aged elderly. This study aimed to evaluate the efficacy and safety of therapeutic ERCP in patients >=80 years of age. METHODS: Patients 80 years of age or older (n = 312) and younger than 65 years (n = 312) who underwent therapeutic ERCP from June 2006 to April 2014 were randomly selected and analyzed retrospectively. The main outcome measurements were therapeutic ERCP related complications and clinical outcomes in the two groups. RESULTS: Choledocholithiasis combined with gallbladder stone was the most common indication for ERCP in both groups. Comorbid diseases (70.5 and 29.8 %, p < 0.001) and the use of anti-thrombotic drugs (18.6 and 1.6 %, p < 0.001) were more frequent in the super-aged group. The mean procedure time was longer, and the frequency of second ERCP was more common in the super-aged group. However, the technical success rate (94.9 and 97.4 %, p = 0.096) and the procedure-related complication rate (4.8 and 5.8 %, p = 0.592) were not different between the two groups. Post-ERCP pancreatitis occurred in 1.3 % of the super-aged group and in 2.9 % of the control group (p = 0.262). Cardiopulmonary complications occurred in 1.9 % of patients in each group (p = 1.0). CONCLUSIONS: Therapeutic ERCP is comparable in terms of efficacy and safety between patients >=80 years and those <65 years of age, although the elderly group had a higher rate of comorbid diseases and used anti-thrombotic drugs more frequently. PMID- 26873538 TI - Distinct Patterns of Colocalization of the CCND1 and CMYC Genes With Their Potential Translocation Partner IGH at Successive Stages of B-Cell Differentiation. AB - The immunoglobulin heavy chain (IGH) locus is submitted to intra-chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter-chromosomal translocations leading to a variety of B cell malignancies. In most Burkitt's and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D-fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR). The CCND1 genes were found very close to the IGH locus in naive B cells and further away after maturation. In contrast, the CMYC alleles became localized closer to an IGH locus at the stage of SHM/CSR. The colocalization observed between the two oncogenes and the IGH locus at successive stages of B-cell differentiation occurred in the immediate vicinity of the nucleolus, consistent with the known localization of the RAGs and AID enzymes whose function has been demonstrated in IGH physiological rearrangements. We propose that the chromosomal events leading to Mantle Cell lymphoma and Burkitt's lymphoma are favored by the colocalization of CCND1 and CMYC with IGH at the time the concerned B cells undergo VDJ recombination or SHM/CSR, respectively. J. Cell. Biochem. 117: 1506-1510, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26873539 TI - Earthworm-mediated synthesis of silver nanoparticles: A potent tool against hepatocellular carcinoma, Plasmodium falciparum parasites and malaria mosquitoes. AB - The development of parasites and pathogens resistant to synthetic drugs highlighted the needing of novel, eco-friendly and effective control approaches. Recently, metal nanoparticles have been proposed as highly effective tools towards cancer cells and Plasmodium parasites. In this study, we synthesized silver nanoparticles (EW-AgNP) using Eudrilus eugeniae earthworms as reducing and stabilizing agents. EW-AgNP showed plasmon resonance reduction in UV-vis spectrophotometry, the functional groups involved in the reduction were studied by FTIR spectroscopy, while particle size and shape was analyzed by FESEM. The effect of EW-AgNP on in vitro HepG2 cell proliferation was measured using MTT assays. Apoptosis assessed by flow cytometry showed diminished endurance of HepG2 cells and cytotoxicity in a dose-dependent manner. EW-AgNP were toxic to Anopheles stephensi larvae and pupae, LC(50) were 4.8 ppm (I), 5.8 ppm (II), 6.9 ppm (III), 8.5 ppm (IV), and 15.5 ppm (pupae). The antiplasmodial activity of EW AgNP was evaluated against CQ-resistant (CQ-r) and CQ-sensitive (CQ-s) strains of Plasmodium falciparum. EW-AgNP IC(50) were 49.3 MUg/ml (CQ-s) and 55.5 MUg/ml (CQ r), while chloroquine IC(50) were 81.5 MUg/ml (CQ-s) and 86.5 MUg/ml (CQ-r). EW AgNP showed a valuable antibiotic potential against important pathogenic bacteria and fungi. Concerning non-target effects of EW-AgNP against mosquito natural enemies, the predation efficiency of the mosquitofish Gambusia affinis towards the II and II instar larvae of A. stephensi was 68.50% (II) and 47.00% (III), respectively. In EW-AgNP-contaminated environments, predation was boosted to 89.25% (II) and 70.75% (III), respectively. Overall, this research highlighted the EW-AgNP potential against hepatocellular carcinoma, Plasmodium parasites and mosquito vectors, with little detrimental effects on mosquito natural enemies. PMID- 26873542 TI - Dimensions of Health and Empowerment Programs. PMID- 26873541 TI - The robotic metroplasty in a patient with hybrid septate variant anomaly. AB - Complete uterovaginal septum is unusually associated with an obstructed left hemivagina and hemiuteri. Herein we present a case report of "hybrid septate variant" anomaly diagnosed in a 16-year-old girl. The uterine septum could not be completely removed hysteroscopically because of the obstructed vagina and thick uterine septum; therefore an abdominal approach, robotic metroplastic surgery was performed. We propose that the robotic technology has advantages over the classical laparoscopy related with the surgical correction of Mullerian anomaly. PMID- 26873540 TI - Proteomic characterization of the internalization of Opisthorchis viverrini excretory/secretory products in human cells. AB - The association between liver fluke infection caused by Opisthorchis viverrini and cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium) has been well established. Multiple mechanisms play a role in the development of CCA, but the excretory/secretory products released by O. viverrini (OvES) represent the major interface between the parasite and its host, and their uptake by biliary epithelial cells has been suggested to be responsible for proliferation of cholangiocytes, the cells that line the biliary epithelium. Despite recent progress in the study of the molecular basis of O. viverrini-host interactions, little is known about the effects that OvES induces upon internalization by host cells. In the present study we incubated non-cancerous human cholangiocytes (H69) and human colon cancer (CaCo-2) cells with OvES and performed a time-course quantitative proteomic analysis on the cells to determine the early changes induced by the parasite. Different KEGG pathways were altered in H69 cells compared to Caco-2 cells: glycolysis/gluconeogenesis and protein processing in the endoplasmic reticulum. In addition, the Reactome pathway analysis showed a predominance of proteins involved in cellular pathways related to apoptosis and apoptotic execution phase in H69 cells after incubation with OvES. The present study provides the first proteomic analysis to address the molecular mechanisms by which OvES products interact with host cells, and Sheds light on the cellular processes involved in O. viverrini-induced CCA. PMID- 26873543 TI - News From the International Council on Women's Health Issues. PMID- 26873544 TI - Family involvement in cancer treatment decision-making: A qualitative study of patient, family, and clinician attitudes and experiences. AB - OBJECTIVE: Little is known about how family are involved in cancer treatment decision-making. This study aimed to qualitatively explore Australian oncology clinicians', patients', and family members' attitudes towards, and experiences of, family involvement in decision-making. METHODS: Semi-structured interviews were conducted with 30 cancer patients, 33 family members, 10 oncology nurses and 11 oncologists. Framework analysis methods were used. RESULTS: Three main themes were uncovered: (i) how family are involved in the decision-making process: specific behaviours of family across 5 (extended) decision-making stages; (ii) attitudes towards family involvement in the decision-making process: balancing patient authority with the rights of the family; and (iii) factors influencing family involvement: patient, family, cultural, relationship, and decision. CONCLUSION: This study highlighted many specific behaviours of family throughout the decision-making process, the complex participant attitudes toward retaining patient authority whilst including the family, and insight into influencing factors. These findings will inform a conceptual framework describing family involvement in decision-making. PRACTICE IMPLICATIONS: Clinicians could ascertain participant preferences and remain open to the varying forms of family involvement in decision-making. Given the important role of family in the decision-making process, family inclusive consultation strategies are needed. PMID- 26873545 TI - Online health anxiety and consultation satisfaction: A quantitative exploratory study on their relations. AB - OBJECTIVE: The present study explores how seeking online information may affect satisfaction with the doctor consultation and what role health anxiety plays in this context. METHODS: A survey was conducted asking patients in doctors' offices about their online seeking for health information and measuring health anxiety prior to the consultation, and their satisfaction with the consultation afterwards (N= 239). RESULTS: Results showed that health anxiety is positively related to seeking online health information and that health anxious people are less satisfied with the doctor consultation. Furthermore, people searching more extensively appreciated the duration of their physician's consultation less, but only if they were relatively health anxious. CONCLUSIONS: The internet has significantly changed how patients can prepare themselves prior to the doctor consultation. This may have a negative effect on the satisfaction with the consultation, especially for people that are health anxious. PRACTICAL IMPLICATIONS: Doctors should be aware that online health information seeking affects the satisfaction with the consultation, especially for health anxious individuals. PMID- 26873546 TI - Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice. AB - Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F1 mice given a weekly intravenous dose of 3mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. PMID- 26873547 TI - Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats. AB - Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease. PMID- 26873548 TI - Bears Arouse Interest in Microbiota's Role in Health. AB - The first report of the effect of hibernation on the gut microbiota of bears reveals trends both similar and distinct from those found in small hibernators. A model mouse system also suggested possible roles of the microbiota for healthy weight gain and insulin tolerance in bears during their active season. PMID- 26873549 TI - Sever lower gastro-intestinal bleeding by CMV in a kidney transplant with low dose immunosuppression. PMID- 26873550 TI - Glycaemic changes in patients with chronic kidney disease. AB - In Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records. OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation. Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR=1.033 per cm; 95% CI, 1.005 to 1.062; P=.019) and with conservative treatment vs. replacement therapy (OR=0.41; 95% CI: 0.19-0.92; P=.028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference. OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality. PMID- 26873551 TI - Dexamethasone-induced acute excitotoxic cell death in the developing brain. AB - There is substantial evidence that the use of glucocorticoids in neonates is associated with an increased risk of neurodevelopmental disorders. However, it remains unclear how treatment with low doses of dexamethasone (DEX) may result in behavioral abnormalities without evident signs of immediate neurotoxicity in the neonatal brain. It is possible that cells vulnerable to the pro-apoptotic effects of low doses of DEX escaped detection due to their small number in the developing brain. In agreement with this suggestion, low-dose DEX treatment (0.2mg/kg) failed to induce apoptosis in the cortex or hippocampus proper of neonatal rats. However, this treatment was capable of inducing apoptosis specifically in the dorsal subiculum via a two-step mechanism that involves glutamate excitotoxicity. Application of DEX leads to increased activity of CA1/CA3 hippocampal MAP2 positive neurons, as determined by c-Fos expression at 0.5-1h after DEX injection. Five hours later, the apoptotic markers (fragmented nuclei, active caspase-3 and TUNEL labeling) increased in the dorsal subiculum, which receives massive glutamatergic input from CA1 neurons. Pretreatment with memantine, an antagonist of glutamate NMDA receptors, dose dependently blocked the DEX-induced expression of apoptotic markers in the subicular neurons and astrocytes. These findings provide new insights into the mechanisms of DEX-induced neurotoxicity as well as on the mechanism of therapeutic action of antagonists of NMDA receptors against neurobehavioral disorders caused by neonatal exposure to glucocorticoids. PMID- 26873553 TI - Water-related environments: a multistep procedure to assess the diversity and enzymatic properties of cultivable bacteria. AB - Studying the culturable portion of environmental bacterial populations is valuable for understanding the ecology, for discovering taxonomically interesting isolates and for exploiting their enzymatic abilities. In this study, diverse water-related samples, iced water (3 degrees C) from river, the sediment (29 degrees C) and water (55 degrees C) of a hot-spring, were investigated by two cultivation strategies, Dry and novel Wet approach. The isolates were clustered by fluorescent internal transcribed spacer PCR and identified by 16S rRNA sequencing. Several bacterial groups were also sub-typed through the application of Random Amplified Microsatellite Polymorphisms method. A broad enzymatic screening of all bacterial isolates was performed in order to assess the proteolytic, cellulolytic, lipolytic, esterolytic, amylolytic properties, as well as catalase and peroxidase activities. The Wet cultivation demonstrated to be suitable for the isolation of potential new species belonging to genera Massilia, Algoriphagus, Rheinheimera and Pandoraea. Valuable microbial resources with extensive enzymatic activities were recognized among the psychrophilic (Pantoea brenneri and Serratia sp.), mesophilic (Pandoraea, Massilia, Pseudomonas, Stenotrophomonas, Bacillus and Aeromonas) and thermophilic bacteria (Aeribacullus pallidus and Geobacillus kaustophilus). The experimental strategy developed in this study includes simple investigation tools able to reveal the genetic and enzymatic peculiarities of isolated microorganisms. It can be applied to different kinds of aquatic samples and extreme environments similar to those described in this study. PMID- 26873552 TI - Depdc5 knockout rat: A novel model of mTORopathy. AB - DEP-domain containing 5 (DEPDC5), encoding a repressor of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies and focal cortical dysplasia. Here we established a global knockout rat using TALEN technology to investigate in vivo the impact of Depdc5-deficiency. Homozygous Depdc5(-/-) embryos died from embryonic day 14.5 due to a global growth delay. Constitutive mTORC1 hyperactivation was evidenced in the brains and in cultured fibroblasts of Depdc5(-/-) embryos, as reflected by enhanced phosphorylation of its downstream effectors S6K1 and rpS6. Consistently, prenatal treatment with mTORC1 inhibitor rapamycin rescued the phenotype of Depdc5(-/-) embryos. Heterozygous Depdc5(+/-) rats developed normally and exhibited no spontaneous electroclinical seizures, but had altered cortical neuron excitability and firing patterns. Depdc5(+/-) rats displayed cortical cytomegalic dysmorphic neurons and balloon-like cells strongly expressing phosphorylated rpS6, indicative of mTORC1 upregulation, and not observed after prenatal rapamycin treatment. These neuropathological abnormalities are reminiscent of the hallmark brain pathology of human focal cortical dysplasia. Altogether, Depdc5 knockout rats exhibit multiple features of rodent models of mTORopathies, and thus, stand as a relevant model to study their underlying pathogenic mechanisms. PMID- 26873554 TI - Effects of neutrophils peptide-1 transgenic Chlorella ellipsoidea on the gut microbiota of male Sprague-Dawley rats, as revealed by high-throughput 16S rRNA sequencing. AB - Rabbit neutrophils peptide-1 (NP-1) is a type of defensin that possesses a broad spectrum of antimicrobial activity. Chlorella ellipsoidea is a new eukaryotic expression system for exogenously producing NP-1. The NP-1 transgenic C. ellipsoidea can be directly added into feed as antimicrobial agent without any purification procedure for the NP-1 peptide. However, the effects of C. ellipsoidea and NP-1 on the host gut microbiota should be explored before application. In this study, diets containing different concentrations (1.25, 2.5, and 5%) of C. ellipsoidea and NP-1 transgenic C. ellipsoidea were administered to male Sprague-Dawley rats. Compared with the chow diet control group, none of the experimental groups showed any significant differences in their growth indices, and no histopathological damage was observed. The phylotypes of gut microbiota in the control group, the 5% C. ellipsoidea diet group and the 5% NP-1 transgenic C. ellipsoidea diet group were determined by 16S rRNA sequencing. The results showed that both 5% experimental groups had shifted community memberships of gut microbiota. In particular, the 5% NP-1 transgenic C. ellipsoidea diet exhibited an increased abundance of most Gram-positive bacterial taxa and a reduced abundance of most Gram-negative bacterial taxa, and it promoted the growth of some lactic acid bacterial genera. Lactic acid bacteria, especially the Bifidobacterium and Lactobacillus, have been widely reported to be benefic effects on the host. Thus NP-1 transgenic C. ellipsoidea is promising feed additive and gut regulator, as it have the potential to increase the abundance of Bifidobacterium and Lactobacillus in gut microbiota of animal. PMID- 26873555 TI - Antifungal performance of extracellular chitinases and culture supernatants of Streptomyces galilaeus CFFSUR-B12 against Mycosphaerella fijiensis Morelet. AB - The tropical and mycoparasite strain Streptomyces galilaeus CFFSUR-B12 was evaluated as an antagonist of Mycosphaerella fijiensis Morelet, causal agent of the Black Sigatoka Disease (BSD) of banana. On zymograms of CFFSUR-B12 culture supernatants, we detected four chitinases of approximately 32 kDa (Chi32), 20 kDa (Chi20), and two with masses well over 170 kDa (ChiU) that showed little migration during denaturing electrophoresis at different concentrations of polyacrylamide. The thymol-sulphuric acid assay showed that the ChiU were glycosylated chitinases. Moreover, matrix assisted laser desorption ionization time-of-flight MS analysis revealed that the ChiU are the same protein and identical to a family 18 chitinase from Streptomyces sp. S4 (gi|498328075). Chi32 was similar to an extracellular protein from Streptomyces albus J1074 (gi|478687481) and Chi20 was non-significantly similar to chitinases from five different strains of Streptomyces (P > 0.05). Subsequently, Chi32 and Chi20 were partially purified by anion exchange and hydrophobic interaction chromatography and tested against M. fijiensis. Chitinases failed to inhibit ascospore germination, but inhibited up to 35 and 62% of germ tube elongation and mycelial growth, respectively. We found that crude culture supernatant and living cells of S. galilaeus CFFSUR-B12 were the most effective in inhibiting M. fijiensis and are potential biocontrol agents of BSD. PMID- 26873556 TI - chr genes from adaptive replicons are responsible for chromate resistance by Burkholderia xenovorans LB400. AB - The chromate ion transporter (CHR) superfamily includes proteins that confer chromate resistance by extruding toxic chromate ions from cytoplasm. Burkholderia xenovorans strain LB400 encodes six CHR homologues in its multireplicon genome and has been reported as highly chromate-resistant. The objective of this work was to analyze the involvement of chr redundant genes in chromate resistance by LB400. It was found that B. xenovorans plant rhizosphere strains lacking the megaplasmid are chromate-sensitive, suggesting that the chr gene present in this replicon is responsible for the chromate-resistance phenotype of the LB400 strain. Transformation of a chromate-sensitive B. xenovorans strain with each of the six cloned LB400 chr genes showed that genes from 'adaptive replicons' (chrA1b and chr1NCb from chromosome 2 and chrA2 from the megaplasmid) conferred higher chromate resistance levels than chr genes from 'central' chromosome 1 (chrA1a, chrA6, and chr1NCa). An LB400 insertion mutant affected in the chrA2 gene displayed a chromate-sensitive phenotype, which was fully reverted by transferring the chrA2 wild-type gene, and partially reverted by chrA1b or chr1NCb genes. These data indicate that chr genes from adaptive replicons, mainly chrA2 from the megaplasmid, are responsible for the B. xenovorans LB400 chromate resistance phenotype. PMID- 26873557 TI - Enhanced production of tetramethylpyrazine in Bacillus licheniformis BL1 by bdhA disruption and 2,3-butanediol supplementation. AB - The 2,3-butanediol (2,3-BD) dehydrogenase gene (bdhA) of Bacillus licheniformis BL1 was disrupted to construct the tetramethylpyrazine (TMP)-producing BLA strain. During microaerobic fermentation, the bdhA-disrupted BLA strain produced 46.98 g TMP/l, and this yield was 23.99% higher than that produced by the parent BL1 strain. In addition, the yield of acetoin, which is a TMP precursor, also increased by 28.98% in BLA. The TMP production by BL1 was enhanced by supplementing the fermentation medium with 2,3-BD. The yield of TMP improved from 37.89 to 44.77 g/l as the concentration of 2,3-BD increased from 0 to 2 g/l. The maximum TMP and acetoin yields increased by 18.16 and 17.87%, respectively with the increase in 2,3-BD concentration from 0 to 2 g/l. However, no increase was observed when the concentration of 2,3-BD in the matrix was >=3 g/l. This study provides a valuable strategy to enhance TMP and acetoin productivity of mutagenic strains by gene manipulation and optimizing fermentation conditions. PMID- 26873558 TI - Production of bacteriocin by Virgibacillus salexigens isolated from "terasi": a traditionally fermented shrimp paste in Indonesia. AB - A natural antibacterial-substance-producing gram-positive bacterium was isolated from terasi shrimp paste, a popular fermented product in Indonesia. This strain, a spore-forming and strictly aerobic bacterium, was identified as Virgibacillus salexigens by 16S rRNA gene sequence analysis. The antibacterial substance purified from the precipitated product in the culture supernatant of the strain using ammonium sulfate showed a broad inhibition spectrum against gram-positive bacteria, including a typical foodborne bacterium, namely, Listeria monocytogenes. The antibacterial activity of the substance was inactivated by treatments with various proteolytic enzymes. It was stable after heating or pH treatment, and approximately 60% of the initial activity remained even after heating at 121 degrees C for 15 min. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis indicated that its monoisotopic mass weight was 5318.4 Da (M+H)(+). On the basis of the results obtained by the automated Edman degradation technique and MALDI TOF MS analysis, the substance can be classified as a member of Class IId bacteriocins, but it could not be identified as any of the previously purified substances except for the putative bacteriocin predicted from the draft genome sequence data of gram-positive bacteria such as Virgibacillus and Bacillus strains. PMID- 26873559 TI - Unique sequence characteristics account for good DGGE separation of almost full length 18S rDNAs. AB - A major limiting factor for DGGE-based microbial community studies is that the fragments should not be much longer than 500 bp for successful analysis. However, relatively high-resolution was achieved based on DGGE of the long 18S rDNA fragment (>1500 bp), which might be surprising due to the known decrease in DGGE resolution of DNA molecules with large melted regions. A unique sequence characteristic was found in a specific region (ca. 275 bp, named the NS1-end region) of 18S rDNAs, and fungal communities separated from Hong Qu glutinous rice wine brewing system was used to reveal the relationship between high resolution capacity and the unique sequence characteristics. The results showed that DGGE separation of the long 18S rDNA fragments depended on their NS1-end regions. The region is composed of a sequence-variable and short-length GC-poor region (ca. 160 bp) and a GC-rich region (ca. 110 bp), which contribute to the high resolution capacity achieved for DGGE of the long 18S rDNA fragments. Thus DGGE of the long 18S rDNA fragment is recommended as a target fragment for studies of fungal communities whose 18S rDNAs possess similar sequence characteristics. Good resolution and almost full-length 18S rDNA sequences can thus be obtained to provide more accurate and reliable analysis of fungal communities. Since more sequences are obtained directly from the PCR product through the long rDNA fragment approach, this is a convenient and effective approach for sequence-based analysis without using other complementary methods such as an rDNA clone library method. PMID- 26873560 TI - Selection and characterization of Argentine isolates of Trichoderma harzianum for effective biocontrol of Septoria leaf blotch of wheat. AB - Species of the genus Trichoderma are economically important as biocontrol agents, serving as a potential alternative to chemical control. The applicability of Trichoderma isolates to different ecozones will depend on the behavior of the strains selected from each zone. The present study was undertaken to isolate biocontrol populations of Trichoderma spp. from the Argentine wheat regions and to select and characterize the best strains of Trichoderma harzianum by means of molecular techniques. A total of 84 out of the 240 strains of Trichoderma were able to reduce the disease severity of the leaf blotch of wheat. Thirty-seven strains were selected for the reduction equal to or greater than 50% of the severity, compared with the control. The percentage values of reduction of the pycnidial coverage ranged between 45 and 80%. The same last strains were confirmed as T. harzianum by polymerase chain reaction amplification of internal transcribed spacers, followed by sequencing. Inter-simple sequence repeat was used to examine the genetic variability among isolates. This resulted in a total of 132 bands. Further numerical analysis revealed 19 haplotypes, grouped in three clusters (I, II, III). Shared strains, with different geographical origins and isolated in different years, were observed within each cluster. The origin of the isolates and the genetic group were partially related. All isolates from Parana were in cluster I, all isolates from Loberia were in cluster II, and all isolates from Pergamino and Santa Fe were in cluster III. Our results suggest that the 37 native strains of T. harzianum are important in biocontrol programs and could be advantageous for the preparation of biopesticides adapted to the agroecological conditions of wheat culture. PMID- 26873561 TI - Biotechnological potential of a rhizosphere Pseudomonas aeruginosa strain producing phenazine-1-carboxylic acid and phenazine-1-carboxamide. AB - Bacterial phenazine metabolites belong to a group of nitrogen-containing heterocyclic compounds with antimicrobial activities. In this study, a rhizosphere Pseudomonas aeruginosa strain PA1201 was isolated and identified through 16S rDNA sequence analysis and fatty acid profiling. PA1201 inhibited the growth of various pathogenic microorganisms, including Rhizotonia solani, Magnaporthe grisea, Fusarium graminearum, Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Staphylococcus aureus. High Performance Liquid Chromatography showed that PA1201 produced high levels of phenazine-1 carboxylic acid (PCA), a registered green fungicide 'Shenqinmycin' with the fermentation titers of 81.7 mg/L in pigment producing medium (PPM) and 926.9 mg/L in SCG medium containing soybean meal, corn steep liquor and glucose. In addition, PA1201 produced another antifungal metabolite, phenazine-1-carboxaminde (PCN), a derivative of PCA, with the fermentation titers of 18.1 and 489.5 mg/L in PPM and SCG medium respectively. To the best of our knowledge, PA1201 is a rhizosphere originating P. aeruginosa strain that congenitally produces the highest levels of PCA and PCN among currently reported P. aeruginosa isolates, which endows it great biotechnological potential to be transformed to a biopesticide-producing engineering strain. PMID- 26873563 TI - Where have all the medicines gone? PMID- 26873562 TI - Pregnancy outcomes after exposure to tocilizumab: A retrospective analysis of 61 patients in Japan. AB - OBJECTIVES: To assess the effects of tocilizumab on pregnancy outcomes in Japanese patients with rheumatic disease. METHODS: Data from Chugai's tocilizumab safety database (April 2005 to October 2014) were retrospectively analyzed to identify pregnancy outcomes in patients exposed to tocilizumab. RESULTS: Data were available for 61 pregnancies exposed to tocilizumab, and outcomes were reported for 50 of those pregnancies. In 36 births, no congenital anomalies were identified; however, six neonatal abnormalities were reported: five cases of low birth weight (<2500 g) and one case of neonatal asphyxia. Of 36 births, tocilizumab was resumed during lactation in two patients, with no subsequent adverse events reported in newborns. The spontaneous abortion rate was 18.0% (9 of 50 pregnancies), which is comparable to the rate in the general population. The five terminated pregnancies included one case of caudal regression syndrome. CONCLUSIONS: The present retrospective study of 61 pregnancies exposed to tocilizumab at conception indicated no increased rates of spontaneous abortion or congenital abnormalities in patients with rheumatic disease. However, further study is necessary to confirm the benefit-risk profile of tocilizumab treatment during pregnancy. PMID- 26873564 TI - Use of 3D Electroanatomical Navigation (CARTO-3) to Minimize or Eliminate Fluoroscopy Use in the Ablation of Pediatric Supraventricular Tachyarrhythmias. AB - BACKGROUND: Radiation exposure related to medical procedures carries known medical risk. Electrophysiology (EP) and catheter ablation procedures are traditionally performed under fluoroscopic guidance. Three-dimensional (3D) electroanatomical navigation systems decrease or eliminate fluoroscopy use in EP procedures. OBJECTIVE: The aim of this study was to assess the efficacy and outcome of a minimal or no fluoroscopic electroanatomical mapping approach for catheter ablations for supraventricular tachycardia (SVT) in the pediatric population. METHODS: Patients were identified through our EP database. A retrospective chart review was performed at a single institution. RESULTS: Sixty three pediatric patients underwent catheter ablations with a minimal fluoroscopic and 3D electroanatomical mapping using CARTO-3 system (Biosense Webster, Diamond Bar, CA, USA) between October 2012 and March 2015. We selected 20 age-matched patients who underwent ablations for SVT by the same operator prior to October 2012 with fluoroscopy use as our control group. The mean age in the study and control group was 13.9 years and 13.7 years, respectively. Mean procedure time was 208.7 minutes and 217.2 minutes in the study and control group (P = NS). Thirty-four (54%) in the study group had no fluoroscopy use. Mean fluoroscopy time was 4.1 minutes versus 35.4 minutes between the study and the control group (P < 0.001). Radiation dose was 6.7 mGy versus 209.3 mGy between the study and the control group (P < 0.001). Acute procedural success was achieved in 95% and 90% of patients in the study and control groups, respectively. On follow-up, the recurrence rate was 5.3% in the study group and 5.6% in the control group. CONCLUSION: Catheter ablation for SVT in children can be successfully performed in patients with normal cardiac anatomy using minimal or no fluoroscopy with favorable outcomes. PMID- 26873566 TI - Extranodal natural killer T-cell lymphoma-new profiling, old tricks. PMID- 26873565 TI - A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. AB - BACKGROUND: The clinical outcome of extranodal natural killer T-cell lymphoma (ENKTL) has improved substantially as a result of new treatment strategies with non-anthracycline-based chemotherapies and upfront use of concurrent chemoradiotherapy or radiotherapy. A new prognostic model based on the outcomes obtained with these contemporary treatments was warranted. METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort. FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK E model was only significantly associated with the high-risk group compared with the low-risk group. INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy. FUNDING: Samsung Biomedical Research Institute. PMID- 26873568 TI - Langerhans cell histiocytosis in an adult patient presenting with eruptions on the scalp and trunk accompanied by lytic lesions on the skull. PMID- 26873567 TI - Prevalence of Apical Periodontitis in Endodontically Treated Premolars and Molars with Untreated Canal: A Cone-beam Computed Tomography Study. AB - INTRODUCTION: The purpose of this retrospective cohort study was to evaluate the incidence of missed canals in endodontically treated teeth in the Greater Philadelphia area patient population and to evaluate the effect of untreated canals on endodontic outcome. METHODS: A total of 1397 cone-beam computed tomography (CBCT) volumes taken from January 2013 to July 2015 were investigated. Limited view CBCT images were taken with Kodak 9000 3D System field of view at voxel size, 76 MUm or Morita Veraviewpocs 3D F40 field of view at voxel size, 125 MUm. All root canal-treated premolars and molars were included in the study. Unfilled canals appearing from cementoenamel junction to apex including splitting from a main canal at coronal, mid, or apical third were defined as missed untreated canal. A periapical lesion was diagnosed when disruption of the lamina dura was detected and the low density area associated with the radiographic apex was at least twice the width of the periodontal ligament space. RESULTS: The overall incidence of missed canals was 23.04%. The incidence of missed canals per tooth was highest in tooth #14 at 46.5% and tooth #3 at 41.3%. The incidence of missed canals was highest in the upper molars at 40.1% and lowest in the upper premolars at 9.5%. There was a significant difference in lesion prevalence when a canal was missed-untreated (P < .05). Teeth with a missed canal were 4.38 times more likely to be associated with a lesion. CONCLUSIONS: Limited field-of-view CBCT should be examined before any endodontic retreatment to identify missed canals. This knowledge would not only help clinicians to locate missed canals clinically but would also help in deciding the surgical approach. PMID- 26873569 TI - Is socially integrated community day care for people with dementia associated with higher user satisfaction and a higher job satisfaction of staff compared to nursing home-based day care? AB - OBJECTIVES: To investigate whether community-based (CO) day care with carer support according to the proven effective Meeting Centres Support Programme model is associated with higher satisfaction of people with dementia (PwD) and their informal caregivers (CG) and with a higher job satisfaction among care staff compared to traditional nursing home-based (NH) day care. METHOD: Data were collected in 11 NH day care centres and 11 CO day care centres. User satisfaction of PwD and CG was evaluated in the 11 NH day care centres (nPwD = 41, nCG = 39) and 11 CO day care centres (nPwD = 28, nCG = 36) with a survey after six months of participation. Job satisfaction was measured only in the six NH day care centres that recently transformed to CO day care, with two standard questionnaires before (nSTAFF = 35), and six months after the transition (nSTAFF = 35). RESULTS: PwD were more positive about the communication and listening skills of staff and the atmosphere and activities at the CO day care centre. Also, CG valued the communication with, and expertise of, staff in CO day care higher, and were more satisfied with the received emotional, social and practical support. After the transition, satisfaction of staff with the work pace increased, but satisfaction with learning opportunities decreased. CONCLUSION: PwD and CG were more satisfied about the communication with the staff and the received support in CO day care than in NH day care. Overall job satisfaction was not higher, except satisfaction about work pace. PMID- 26873570 TI - Association of the multi-biomarker disease activity score with joint destruction in patients with rheumatoid arthritis receiving tumor necrosis factor-alpha inhibitor treatment in clinical practice. AB - OBJECTIVE: Evaluate the association between the multi-biomarker disease activity (MBDA) score and radiographic progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF)-alpha inhibitors. METHODS: Change (Delta) in modified total Sharp score (mTSS) over 52 weeks and disease activity scores were examined retrospectively by Spearman's rank correlation coefficient in patients (N = 83) with RA initiating TNF-inhibitor treatment. Relative risk (RR) of DeltamTSS >0.5 for low MBDA score and 28-joint count disease activity score (DAS28) categories and associations between DeltamTSS and MBDA score categories conditional on DAS28 categories were assessed. RESULTS: At 52 weeks, 34% of patients had DeltamTSS >0.5 and 12% had DeltamTSS >3. Strongest correlations were observed between DeltamTSS and MBDA score (r = 0.47) or DAS28 (r = 0.42) at Week 24 and for area under the curve at Week 52 (MBDA score: r = 0.44, DAS28: r = 0.41), all p < 0.001. At Week 24, RR of DeltamTSS >0.5 for moderate/high MBDA score (>=30) or DAS28 (>3.2) were 6.6 (p < 0.001) and 2.7 (p = 0.005), respectively. Low DAS28 had greater risk of DeltamTSS >0.5 at 52 weeks when MBDA score was >=30 (p < 0.05). CONCLUSION: Higher MBDA score or DAS28 at Week 24 was associated with greater radiographic progression over 52 weeks of TNF inhibitor treatment. MBDA score improved risk discrimination for radiographic progression within DAS28 categories. PMID- 26873571 TI - Individual differences in cognitive control over emotional material modulate cognitive biases linked to depressive symptoms. AB - Deficient cognitive control over emotional material and cognitive biases are important mechanisms underlying depression, but the interplay between these emotionally distorted cognitive processes in relation to depressive symptoms is not well understood. This study investigated the relations among deficient cognitive control of emotional information (i.e. inhibition, shifting, and updating difficulties), cognitive biases (i.e. negative attention and interpretation biases), and depressive symptoms. Theory-driven indirect effect models were constructed, hypothesising that deficient cognitive control over emotional material predicts depressive symptoms through negative attention and interpretation biases. Bootstrapping analyses demonstrated that deficient inhibitory control over negative material was related to negative attention bias which in turn predicted a congruent bias in interpretation and subsequently depressive symptoms. Both shifting and updating impairments in response to negative material had an indirect effect on depression severity through negative interpretation bias. No evidence was found for direct effects of deficient cognitive control over emotional material on depressive symptoms. These findings may help to formulate an integrated understanding of the cognitive foundations of depressive symptoms. PMID- 26873572 TI - In vitro selection of DNA aptamers binding pesticide fluoroacetamide. AB - Fluoroacetamide (Mw = 77.06) is a lethal rodenticide to humans and animals which is still frequently abused in food storage somewhere in China. The production of antibodies for fluoroacetamide is difficult due to its high toxicity to animals, which limits the application of immunoassay method in poison detection. In this work, aptamers targeting N-fluoroacetyl glycine as an analog of fluoroacetamide were selected by a specific systematic evolution of ligands by exponential enrichment (SELEX) strategy. The binding ability of the selected aptamers to fluoroacetamide was identified using surface plasmon resonance (SPR)-based assay. The estimated KD values in the low micromolar range showed a good affinity of these aptamers to the target. Our work verified that the SELEX strategy has the potential for developing aptamers targeted to small molecular toxicants and aptamers can be employed as new recognition elements instead of antibodies for poison detection. PMID- 26873573 TI - Apoptotic Cells Release IL1 Receptor Antagonist in Response to Genotoxic Stress. AB - Apoptosis is a controlled means of eliminating damaged cells without causing an inflammatory response or tissue damage. The mechanisms that contribute to the suppression of an inflammatory response upon apoptosis of cells are poorly understood. Here, we report that apoptotic cells release the interleukin-1 receptor antagonist (IL1RA). The release of IL1RA depended on the DNA damage response, caspase 9, and caspase 3.De novotranslation, classical secretion pathways, or N-glycosylation was not required for the release of IL1RA. The amounts of IL1RA released by apoptotic cells impaired IL1-induced expression of IL6 In summary, we demonstrate that the release of IL1RA in response to genotoxic stress contributes to the immunosuppressive effects of apoptotic cells. PMID- 26873574 TI - Phase I/II Study of Metastatic Melanoma Patients Treated with Nivolumab Who Had Progressed after Ipilimumab. AB - The checkpoint inhibitor nivolumab is active in patients with metastatic melanoma who have failed ipilimumab. In this phase I/II study, we assessed nivolumab's safety in 92 ipilimumab-refractory patients with unresectable stage III or IV melanoma, including those who experienced grade 3-4 drug-related toxicity to ipilimumab. We report long-term survival, response duration, and biomarkers in these patients after nivolumab treatment (3 mg/kg) every 2 weeks for 24 weeks, then every 12 weeks for up to 2 years, with or without a multipeptide vaccine. The response rate for ipilimumab-refractory patients was 30% (95% CI, 21%-41%). The median duration of response was 14.6 months, median progression-free survival was 5.3 months, and median overall survival was 20.6 months, when patients were followed up for a median of 16 months. One- and 2-year survival rates were 68.4% and 31.2%, respectively. Ipilimumab-naive and ipilimumab-refractory patients showed no significant difference in survival. The 21 patients with prior grade 3 4 toxicity to ipilimumab that was managed with steroids tolerated nivolumab well, with 62% (95% CI, 38%-82%) having complete or partial responses or stabilized disease at 24 weeks. High numbers of myeloid-derived suppressor cells (MDSC) were associated with poor survival. Thus, survival and long-term safety were excellent in ipilimumab-refractory patients treated with nivolumab. Prior grade 3-4 immune related adverse effects from ipilimumab were not indicative of nivolumab toxicities, and patients had a high overall rate of remission or stability at 24 weeks. Prospectively evaluating MDSC numbers before treatment could help assess the expected benefit of nivolumab. PMID- 26873575 TI - Outcomes of endoscopic cricopharyngeal myotomy with CO2 laser surgery: A retrospective study of 47 patients. AB - BACKGROUND: Endoscopic cricopharyngeal myotomy (ECPM) using CO2 laser surgery presents a less invasive treatment technique when compared to transcervical cricopharyngeal myotomy. METHODS: Forty-seven patients who underwent ECPM from 2002 until 2013 were included in this study. Patient characteristics, and preoperative and postoperative outcome and complications were scored by retrospective chart review and by using the Deglutition Handicap Index (DHI). RESULTS: Overall, 40 of 47 patients (85%) experienced relief of symptoms postoperatively. Ten patients (25%) developed recurrent symptoms of dysphagia requiring re-laser surgery. All 40 patients were satisfied at the postoperative visit after an average of 1.3 interventions. DHI scores were better in patients with idiopathic dysfunction and neurologic disease, compared to dysfunction because of prior treatment of head and neck cancer. One patient developed mediastinitis that was successfully treated with antibiotics. There was no mortality. CONCLUSION: ECPM is an effective treatment for cricopharyngeal dysfunction with a low rate of surgical morbidity and complications. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1022-1027, 2016. PMID- 26873576 TI - A method to determine the mode of binding for GCPII inhibitors using bio-layer interferometry. AB - The rapid dilution of the enzyme-inhibitor complex assay to monitor the recovery of enzyme activity is a well-established assay to determine the reversibility of inhibition. Our laboratory has previously employed this method to ascertain the reversibility of known glutamate carboxypeptidase II (GCPII)-targeting agents. Due to the tedious and time-consuming nature of the assay, we sought to develop a facile method to determine the reversibility of well-characterized GCPII inhibitors using bio-layer interferometry (BLI). The results from the BLI assay are in agreement with the rapid dilution method. Herein, we report for the first time, a rapid, novel real-time BLI method to determine reversibility of inhibition. PMID- 26873577 TI - Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations. AB - A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (alpha) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect alpha estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, alpha = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield alpha-hat (estimated alpha) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, alpha-hat < alpha. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating alpha. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with alpha-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees. PMID- 26873578 TI - Expression Divergence Is Correlated with Sequence Evolution but Not Positive Selection in Conifers. AB - The evolutionary and genomic determinants of sequence evolution in conifers are poorly understood, and previous studies have found only limited evidence for positive selection. Using RNAseq data, we compared gene expression profiles to patterns of divergence and polymorphism in 44 seedlings of lodgepole pine (Pinus contorta) and 39 seedlings of interior spruce (Picea glauca * engelmannii) to elucidate the evolutionary forces that shape their genomes and their plastic responses to abiotic stress. We found that rapidly diverging genes tend to have greater expression divergence, lower expression levels, reduced levels of synonymous site diversity, and longer proteins than slowly diverging genes. Similar patterns were identified for the untranslated regions, but with some exceptions. We found evidence that genes with low expression levels had a larger fraction of nearly neutral sites, suggesting a primary role for negative selection in determining the association between evolutionary rate and expression level. There was limited evidence for differences in the rate of positive selection among genes with divergent versus conserved expression profiles and some evidence supporting relaxed selection in genes diverging in expression between the species. Finally, we identified a small number of genes that showed evidence of site-specific positive selection using divergence data alone. However, estimates of the proportion of sites fixed by positive selection (alpha) were in the range of other plant species with large effective population sizes suggesting relatively high rates of adaptive divergence among conifers. PMID- 26873579 TI - Mechanisms of vascularization in murine models of primary and metastatic tumor growth. AB - Directed capillary ingrowth has long been considered synonymous with tumor vascularization. However, the vasculature of primary tumors and metastases is not necessarily formed by endothelial cell sprouting; instead, malignant tumors can acquire blood vessels via alternative vascularization mechanisms, such as intussusceptive microvascular growth, vessel co-option, and glomeruloid angiogenesis. Importantly, in response to anti-angiogenic therapies, malignant tumors can switch from one vascularization mechanism to another. In this article, we briefly review the biological features of these mechanisms and discuss on their significance in medical oncology. PMID- 26873580 TI - A concise review of the bioanalytical methods for the quantitation of sitagliptin, an important dipeptidyl peptidase-4 (DPP4) inhibitor, utilized for the characterization of the drug. AB - Inhibition of dipeptidyl peptidase-4 (DPP4) is an emerging therapeutic approach for treating type 2 diabetes and has revolutionized the concept of diabetes management. Sitagliptin is the first approved orally active, potent, selective and nonpeptidomimetic DPP4 inhibitor. Incidence of hypoglycemia and weight gain is negligible with sitagliptin treatment. It is used as monotherapy or in combination with other anti-diabetic drugs to treat type 2 diabetes. There are numerous bioanalytical methods published for the analysis of sitagliptin in preclinical and clinical samples. This review focuses on the various HPLC and LC MS/MS methods that have been used to analyze sitagliptin in various biological matrices. A small section is devoted to the bioanalysis of other DPP4 inhibitors such as vildagliptin, saxagliptin and linagliptin. This review provides key information in a concise manner regarding sample processing options, chromatographic/detection conditions and validation parameters of the chosen methods for sitagliptin and other DPP4 inhibitors. PMID- 26873581 TI - Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice. AB - BACKGROUND: Macrophages are involved in demyelination in many brain diseases. However, the role of macrophages in the recovery phase of the ischemic brain is unknown. The present study aims to explore the role of macrophages in the ischemic brain injury and tissue repair following a 90-min transient middle cerebral artery occlusion in mice. METHODS: Clodronate liposomes were injected into mice to deplete periphery macrophages. These mice subsequently underwent middle cerebral artery occlusion. F4/80(+) and CD68(+) cells were examined in the mouse spleen and brain to confirm macrophage depletion at 14 days after middle cerebral artery occlusion. Modified neurological severity scores were used to evaluate the behavioral function between 1 and 14 days after middle cerebral artery occlusion. MBP, Iba1, and CD31 immunostaining were performed to determine myelin lesion, microglia activation, and microvessel density. RESULTS: Clodronate liposomes depleted 80 % of the macrophages in the mouse spleen and reduced macrophage infiltration in the mouse brain. Macrophage depletion reduced the myelin damage in the ipsilateral striatum and microglia activation in both the ipsilateral cortex and striatum, enhanced the microvessel density in the peri infarct region, attenuated brain atrophy, and promoted neurological recovery following middle cerebral artery occlusion. CONCLUSIONS: Our results suggested that macrophage depletion is a potential intervention that can promote tissue repair and remodeling after brain ischemia, reduce demyelination and microglia activation, and enhance focal microvessel density. PMID- 26873583 TI - Short-chain C2 ceramide induces heme oxygenase-1 expression by upregulating AMPK and MAPK signaling pathways in rat primary astrocytes. AB - Ceramide belongs to the group of sphingolipid metabolites that are produced in the brain and peripheral systems and act as intracellular second messengers. Although some physiological roles of ceramide have been reported in the brain, the role of ceramide in astrocytes has not been clearly demonstrated. In the present study, we investigated the antioxidant effects of the cell-permeable short-chain C2 ceramide in rat brain astrocytes. C2 ceramide inhibited hydrogen peroxide-induced reactive oxygen species generation and subsequent cell death in rat primary astrocytes. C2 ceramide increased the expression of phase II antioxidant enzymes, such as heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO1), and superoxide dismutase (SOD) that are under the control of Nrf2/ARE signaling pathways. Detailed mechanistic studies revealed that C2 ceramide increased the nuclear translocation and DNA binding of nuclear factor-E2-related factor 2 (Nrf2) and c-Jun to the antioxidant response element (ARE), and increased ARE-mediated transcriptional activity. Moreover, C2 ceramide increased the interaction between Nrf2 and c-Jun as shown by antibody co immunoprecipitation assay. Further analysis of signaling pathways revealed that AMPK and MAP kinases are involved in HO-1 expression by modulating ARE-mediated transcriptional activity. Therefore, the upregulation of antioxidant enzymes by C2 ceramide may be a potential therapeutic modality for neurodegenerative diseases that are accompanied by oxidative stress. PMID- 26873582 TI - Health behavior change benefits: Perspectives of Latinos with serious mental illness. AB - The objective of this study was to explore the perceived benefits of engaging in health behavior change from the viewpoint of overweight and obese Latinos with severe mental illness (SMI) enrolled in the U.S. Qualitative, semistructured interviews were conducted with 20 obese Latinos with SMI who were enrolled in a randomized trial evaluating the effectiveness of a motivational health promotion intervention adapted for persons with SMI. Overweight and obese Latino participants believed that engaging in health behavior change would have both physical and mental health benefits, including chronic disease management, changes in weight and body composition, and increased self-esteem. Interventions that explicitly link physical activity and healthy eating to improvements in mental health and well-being may motivate Latinos with SMI to adopt health behavior change. PMID- 26873584 TI - Incidence of venous thromboembolism and hemorrhage related safety studies of preoperative anticoagulation therapy in hip fracture patients undergoing surgical treatment: a case-control study. AB - BACKGROUND: Venous thromboembolism is a common postoperative complication following orthopedic surgeries, with morbid and potentially fatal consequences. Perioperative low-molecular-weight heparin (LMWH) therapy can reduce the incidence of venous thromboembolism, but may also increase the risk of bleeding complications. Current literature reflects the need to balance the improved efficacy of early initiating prophylaxis with increased risk of perioperative bleeding. The purpose of this study was to compare the effectiveness and hemorrhage related safety of preoperative versus postoperative LMWH therapy for prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE) in hip fracture patients. METHODS: We retrospectively evaluated 222 patients who underwent surgical treatment at Peking University People's Hospital between January 2009 and December 2010. Patients were allocated to two groups, receiving either preoperative or postoperative initiation of LMWH therapy for venous thromboembolism prophylaxis. Preoperative anticoagulation therapy was initiated 1 12 days prior to surgery (133 patients), and postoperative anticoagulation therapy was initiated 12 h after completion of surgery (89 patients). The preoperative group was further subdivided into four subgroups according to the time of initiation of therapy: 1-3 days before surgery (group A, 54 patients), 4 6 days before surgery (group B, 57 patients), 7-9 days before surgery (group C, 15 patients), and 10-12 days before surgery (group D, 7 patients). Occurrences of DVT, PE, adverse drug effects, intraoperative and postoperative bleeding were recorded, along with concentrations of preoperative and postoperative hemoglobin and length of hospital stay. The above parameters were compared between groups. RESULTS: Among recipients of preoperative anticoagulation therapy, two patients developed postoperative PE (1.5 %), one patient developed DVT (0.75 %). In the group receiving postoperative initiation of anticoagulation therapy, one patient each developed PE and DVT (1.1 %, 1.1 %). There was no difference in the occurrence of PE and DVT between the two groups (P>0.05, Chi-square tests). We identified the incidences of major bleeding, minor bleeding, and intraspinal hematoma after spinal anesthesia, which were 0 %/0 %, 3.76 %/3.37 %, and 0 %/0 %, respectively in preoperative and postoperative anticoagulation groups. There was no significant difference in the incidence of bleeding complications between patients receiving preoperatively initiated LMWH with patients receiving postoperatively initiated LMWH. Spinal anesthesia was administered to 168 patients, with no cases of postoperative intraspinal hematoma. CONCLUSIONS: Preoperative anticoagulation therapy with LMWH may not increase intraoperative or postoperative blood loss, or the rate of intraspinal hematoma after spinal anesthesia, but also does not significantly reduce the risk of postoperative DVT or PE, compared to postoperative initiation. PMID- 26873585 TI - Longimicrobium terrae gen. nov., sp. nov., an oligotrophic bacterium of the under represented phylum Gemmatimonadetes isolated through a system of miniaturized diffusion chambers. AB - A novel chemo-organoheterotroph bacterium, strain CB-286315T, was isolated from a Mediterranean forest soil sampled at the Sierra de Tejeda, Almijara and Alhama Natural Park, Spain, by using the diffusion sandwich system, a device with 384 miniature diffusion chambers. 16S rRNA gene sequence analyses identified the isolate as a member of the under-represented phylum Gemmatimonadetes, where 'Gemmatirosa kalamazoonensis' KBS708, Gemmatimonas aurantiaca T-27T and Gemmatimonas phototrophica AP64T were the closest relatives, with respective similarities of 84.4, 83.6 and 83.3 %. Strain CB-286315T was characterized as a Gram-negative, non-motile, short to long rod-shaped bacterium. Occasionally, some cells attained an unusual length, up to 35-40 MUm. The strain showed positive responses for catalase and cytochrome-c oxidase and division by binary fission, and exhibited an aerobic metabolism, showing optimal growth under normal atmospheric conditions. Strain CB-286315T was also able to grow under micro-oxic atmospheres, but not under anoxic conditions. The strain is a slowly growing bacterium able to grow under low nutrient concentrations. Major fatty acids included iso-C17 : 1omega9c, summed feature 3 (C16 : 1omega7c and/or iso-C15 : 0 2-OH), C16 : 0 and iso-C17 : 0. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified glycolipids and three phospholipids. The major isoprenoid quinone was MK-8 and the diagnostic diamino acid was meso-diaminopimelic acid. The DNA G+C content was 67.0 mol%. Based on a polyphasic taxonomic characterization, strain CB-286315T represents a novel genus and species, Longimicrobium terrae gen. nov., sp. nov., within the phylum Gemmatimonadetes. The type strain of Longimicrobium terrae is strain CB 286315T ( = DSM 29007T = CECT 8660T). In order to classify the novel taxon within the existing taxonomic framework, the family Longimicrobiaceae fam. nov., order Longimicrobiales ord. nov. and class Longimicrobia classis nov. are also proposed. PMID- 26873586 TI - Abnormal brain temperature in early-onset Parkinson's disease. PMID- 26873587 TI - Functional structure and antimicrobial activity of persulcatusin, an antimicrobial peptide from the hard tick Ixodes persulcatus. AB - BACKGROUND: Antimicrobial peptides (AMPs) are considered promising candidates for the development of novel anti-infective agents. In arthropods such as ticks, AMPs form the first line of defense against pathogens in the innate immune response. Persulcatusin (IP) was found in the Ixodes persulcatus midgut, and its amino acid sequence was reported. However, the complete structure of IP has not been identified. We evaluated the relation between structural features and antimicrobial activity of IP, and its potential as a new anti-methicillin resistant Staphylococcus aureus (MRSA) agent. METHODS: The structure of IP was predicted using homology modeling and molecular dynamics. IP and other tick AMPs were synthesized using a solid-phase method and purified by high-performance liquid chromatography. Methicillin-susceptible S. aureus (MSSA) and MRSA were used for the minimum inhibitory concentration (MIC) test and short-time killing assay of IP and other tick peptides. The influence of IP on mammalian fibroblasts and colon epithelial cells and each cell DNA and its hemolytic activity towards human erythrocytes were also examined. RESULTS: In the predicted IP structure, the structure with an S-S bond was more stable than that without an S-S bond. The MIC after 24 h of incubation with IP was 0.156-1.25 MUg/mL for MSSA and 0.625-2.5 MUg/mL for MRSA. Compared with the mammalian antimicrobial peptide and other tick peptides, IP was highly effective against MRSA. Moreover, IP showed a dose dependent bactericidal effect on both MSSA and MRSA after 1 h of incubation. IP had no observable effect on mammalian cell growth or morphology, on each cell DNA and on human erythrocytes. CONCLUSIONS: We predicted the three-dimensional structure of IP and found that the structural integrity was maintained by three S S bonds, which were energetically important for the stability and for forming alpha helix and beta sheet. IP has cationic and amphipathic properties, which might be related to its antimicrobial activity. Furthermore, the antimicrobial activity of IP against MRSA was stronger than that of other antimicrobial peptides without apparent damage to mammalian and human cells, demonstrating its possible application as a new anti-MRSA medicine. PMID- 26873588 TI - Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors. AB - PURPOSE: Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function. METHODS: Twenty-nine subjects with acromegaly (11 males, 52 +/- 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD). RESULTS: IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 +/- 1.1 in patients with active disease versus 0.7 +/- 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 +/- 2.7 % in active acromegaly, 4.4 +/- 3.3 % in controlled acromegaly and 7.5 +/- 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1* ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = -0.44, p = 0.02). CONCLUSIONS: Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors. PMID- 26873589 TI - A new method to measure complexity in binary or weighted networks and applications to functional connectivity in the human brain. AB - BACKGROUND: Networks or graphs play an important role in the biological sciences. Protein interaction networks and metabolic networks support the understanding of basic cellular mechanisms. In the human brain, networks of functional or structural connectivity model the information-flow between cortex regions. In this context, measures of network properties are needed. We propose a new measure, Ndim, estimating the complexity of arbitrary networks. This measure is based on a fractal dimension, which is similar to recently introduced box covering dimensions. However, box-covering dimensions are only applicable to fractal networks. The construction of these network-dimensions relies on concepts proposed to measure fractality or complexity of irregular sets in [Formula: see text]. RESULTS: The network measure Ndim grows with the proliferation of increasing network connectivity and is essentially determined by the cardinality of a maximum k-clique, where k is the characteristic path length of the network. Numerical applications to lattice-graphs and to fractal and non-fractal graph models, together with formal proofs show, that Ndim estimates a dimension of complexity for arbitrary graphs. Box-covering dimensions for fractal graphs rely on a linear log-log plot of minimum numbers of covering subgraph boxes versus the box sizes. We demonstrate the affinity between Ndim and the fractal box-covering dimensions but also that Ndim extends the concept of a fractal dimension to networks with non-linear log-log plots. Comparisons of Ndim with topological measures of complexity (cost and efficiency) show that Ndim has larger informative power. Three different methods to apply Ndim to weighted networks are finally presented and exemplified by comparisons of functional brain connectivity of healthy and depressed subjects. CONCLUSION: We introduce a new measure of complexity for networks. We show that Ndim has the properties of a dimension and overcomes several limitations of presently used topological and fractal complexity-measures. It allows the comparison of the complexity of networks of different type, e.g., between fractal graphs characterized by hub repulsion and small world graphs with strong hub attraction. The large informative power and a convenient computational CPU-time for moderately sized networks may make Ndim a valuable tool for the analysis of biological networks. PMID- 26873590 TI - Vitamin D deficiency as adverse drug reaction? A cross-sectional study in Dutch geriatric outpatients. AB - PURPOSE: Adverse drug reactions as well as vitamin D deficiency are issues of public health concern in older people. However, relatively little is known about the impact of drug use on vitamin D status. Our primary aim is to explore associations between drug use and vitamin D status in older people. Furthermore, prevalences of drug use and vitamin D deficiency are estimated. METHODS: In a population of 873 community-dwelling Dutch geriatric outpatients, we explored the cross-sectional relationships of polypharmacy (>=5 medications concomitantly used), severe polypharmacy (>=10 medications), and use of twenty-one specific drug groups, with serum 25-hydroxyvitamin D (25(OH)D) by analysis of covariance. RESULTS: Overall prevalence of polypharmacy was 65 %, of severe polypharmacy 22 %. Depending on the cut-off value, prevalence of vitamin D deficiency was 49 % (<50 nmol/l) or 77 % (<75 nmol/l). Of the patients using a vitamin D supplement, 17 % (<50 nmol/l) or 49 % (<75 nmol/l) were still deficient. In non-users of supplemental vitamin D, after adjustment for age and gender, negative associations were found for severe polypharmacy, metformin, sulphonamides and urea derivatives (SUDs), vitamin K antagonists, cardiac glycosides, loop diuretics, potassium-sparing diuretics, ACE inhibitors, and serotonin reuptake inhibitors; for non-selective monoamine reuptake inhibitors (NSMRIs) the association was positive. The most extreme impacts of drug use on adjusted mean 25(OH)D were -19 nmol/l for SUDs and +18 nmol/l for NSMRIs. CONCLUSION: Drug use should be considered a risk factor for vitamin D deficiency amongst geriatric outpatients. PMID- 26873591 TI - Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly. AB - Pseudouridine (Psi) is the most abundant internal modification identified in RNA, and yet little is understood of its effects on downstream reactions. Yeast U2 snRNA contains three conserved Psis (Psi35, Psi42, and Psi44) in the branch site recognition region (BSRR), which base pairs with the pre-mRNA branch site during splicing. Here, we show that blocks to pseudouridylation at these positions reduce the efficiency of pre-mRNA splicing, leading to growth-deficient phenotypes. Restoration of pseudouridylation at these positions using designer snoRNAs results in near complete rescue of splicing and cell growth. These Psis interact genetically with Prp5, an RNA-dependent ATPase involved in monitoring the U2 BSRR-branch site base-pairing interaction. Biochemical analysis indicates that Prp5 has reduced affinity for U2 snRNA that lacks Psi42 and Psi44 and that Prp5 ATPase activity is reduced when stimulated by U2 lacking Psi42 or Psi44 relative to wild type, resulting in inefficient spliceosome assembly. Furthermore, in vivo DMS probing analysis reveals that pseudouridylated U2, compared to U2 lacking Psi42 and Psi44, adopts a slightly different structure in the branch site recognition region. Taken together, our results indicate that the Psis in U2 snRNA contribute to pre-mRNA splicing by directly altering the binding/ATPase activity of Prp5. PMID- 26873592 TI - Molecular basis of ion permeability in a voltage-gated sodium channel. AB - Voltage-gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na(+) ~ Li(+) ? K(+), Ca(2+), Mg(2+)) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones. PMID- 26873594 TI - High mycobacterial diversity in recreational lakes. AB - Although nontuberculous mycobacteria (NTM) are natural inhabitants of freshwater ecosystems, few studies have focused on their distribution in these habitats. Thus, the knowledge about the abundance as well as the composition of NTM remains limited and patchy in these environments. In this context, a prospective study was performed to identify favourable habitats for mycobacteria in two recreational lakes. Mycobacterial density and diversity were measured using quantitative real-time PCR and the MiSeq Illumina platform. For both lakes, five compartments were investigated, i.e. water column, air-water interface, sediment, epilithon and epiphyton biofilms. Nontuberculous mycobacteria were detected in all compartments in large densities and displayed a remarkable diversity. NTM were dominated by fast-growing species. Lakes and compartments appeared to shape mycobacteria assemblage composition as well as their densities. In both lakes, some OTUs assigned to the species level were identified as related to known opportunistic pathogens. PMID- 26873593 TI - Feedback control in planarian stem cell systems. AB - BACKGROUND: In planarian flatworms, the mechanisms underlying the activity of collectively pluripotent adult stem cells (neoblasts) and their descendants can now be studied from the level of the individual gene to the entire animal. Flatworms maintain startling developmental plasticity and regenerative capacity in response to variable nutrient conditions or injury. We develop a model for cell dynamics in such animals, assuming that fully differentiated cells exert feedback control on neoblast activity. RESULTS: Our model predicts a number of whole organism level and general cell biological and behaviours, some of which have been empirically observed or inferred in planarians and others that have not. As previously observed empirically we find: 1) a curvilinear relationship between external food and planarian steady state size; 2) the fraction of neoblasts in the steady state is constant regardless of planarian size; 3) a burst of controlled apoptosis during regeneration after amputation as the number of differentiated cells are adjusted towards their homeostatic/steady state level. In addition our model describes the following properties that can inform and be tested by future experiments: 4) the strength of feedback control from differentiated cells to neoblasts (i.e. the activity of the signalling system) and from neoblasts on themselves in relation to absolute number depends upon the level of food in the environment; 5) planarians adjust size when food level reduces initially through increased apoptosis and then through a reduction in neoblast self-renewal activity; 6) following wounding or excision of differentiated cells, different time scales characterize both recovery of size and the two feedback functions; 7) the temporal pattern of feedback controls differs noticeably during recovery from a removal or neoblasts or a removal of differentiated cells; 8) the signaling strength for apoptosis of differentiated cells depends upon both the absolute and relative deviations of the number of differentiated cells from their homeostatic level; and 9) planaria prioritize resource use for cell divisions. CONCLUSIONS: We offer the first analytical framework for organizing experiments on planarian flatworm stem cell dynamics in a form that allows models to be compared with quantitative cell data based on underlying molecular mechanisms and thus facilitate the interplay between empirical studies and modeling. This framework is the foundation for studying cell migration during wound repair, the determination of homeostatic levels of differentiated cells by natural selection, and stochastic effects. PMID- 26873595 TI - The T-plasty: a modified YV-plasty for highly recurrent bladder neck contracture after transurethral surgery for benign hyperplasia of the prostate: clinical outcome and patient satisfaction. AB - OBJECTIVE: To describe a modified surgical technique for treatment of highly recurrent bladder neck contracture (BNC) after transurethral surgery for benign hyperplasia and to evaluate success rate and patient satisfaction of this novel technique. METHODS: Ten patients with highly recurrent BNC and multiple prior attempts of endoscopic treatment underwent the T-plasty. Perioperative complications were recorded and classified according to the Clavien classification. Patient reported functional outcomes were retrospectively analysed using a standardized questionnaire assessing recurrence of stenosis, incontinence, satisfaction and changes in quality of life (QoL). The questionnaires included validated IPSS and SF-8-health survey items. RESULTS: Mean age at the time of surgery was 69.2 years (range 61-79), and the mean follow up was 26 months (range 3-46). No complications grade 3 or higher according to the Clavien classification occurred. Success rate was 100 %. No de novo stress incontinence occurred. Urinary stream was described as very strong to moderate by 80 % of the patients, mean post-operative IPSS-score was 11.3 (range 4-29), and mean post-operative IPSS-QoL was 2.4 (range 1-5). Patients satisfaction was very high or high in 90 %, and QoL improved in 90 %. The SF-8-health survey showed values comparable to the reference population. CONCLUSION: The T-plasty represents a safe and valuable option in treating highly recurrent BNC after surgery for benign hyperplasia. It offers multiple advantages compared to other techniques such as a single-staged approach and the opportunity for reconstruction of a reliable wide bladder neck by usage of two well-vascularized flaps. Success rate, low rate of complications and preservation of continence are highly encouraging. PMID- 26873597 TI - Robotic radical cystectomy: intracorporeal versus extracorporeal versus orthotopic neobladder-Which is better? PMID- 26873596 TI - Intermediate-term cancer control outcomes in prostate cancer patients treated with robotic-assisted laparoscopic radical prostatectomy: a multi-institutional analysis. AB - PURPOSE: Cancer control outcomes following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) remain inadequately addressed over intermediate term (>=5-year) follow-up. We examined biochemical recurrence-free survival (BCRFS), clinical recurrence-free survival (CRFS), and cancer-specific survival (CSS) in a multi-institutional cohort of men undergoing RARP for localized PCa. MATERIALS AND METHODS: A total of 5670 PCa patients undergoing RARP +/- pelvic lymph node dissection as primary treatment modality at three tertiary care centers between 2001 and 2010 were analyzed. BCRFS, CRFS, and CSS were estimated using the Kaplan-Meier method. Cox proportional hazards model tested their association with available preoperative and postoperative parameters. RESULTS: 43.6 and 15.1 % of patients had D'Amico intermediate- and high-risk disease, respectively. Over a mean (median) follow-up of 56 (50.4) months, 797 men had a BCR, 78 men had CR, and 32 men died of PCa. Actuarial BCRFS, CRFS, and CSS, respectively, were 83.3, 98.6, and 99.5 % at 5-year; 76.5, 97.5, and 98.7 % at 8 year; and 73.3, 96.7, and 98.4 % at 10-year follow-ups. Only 1.7 % of patients received any adjuvant treatment. Preoperative prostate-specific antigen (PSA) and biopsy Gleason score (GS) were independent clinical predictors of BCRFS, CRFS, and CSS, while postoperatively positive surgical margin, pathological GS, pathological stage, and lymph node invasion were significantly associated with BCR and CR (all p < 0.05). CONCLUSIONS: Cancer control outcomes of RARP appear comparable to those reported for open and laparoscopic RP in previous literature, despite low overall rate of adjuvant treatment. Disease severity and preoperative PSA may aid in risk prognostication and defining postoperative follow-up protocols. PMID- 26873598 TI - Epistasis analysis of 16S rRNA ram mutations helps define the conformational dynamics of the ribosome that influence decoding. AB - The ribosome actively participates in decoding, with a tRNA-dependent rearrangement of the 30S A site playing a key role. Ribosomal ambiguity (ram) mutations have mapped not only to the A site but also to the h12/S4/S5 region and intersubunit bridge B8, implicating other conformational changes such as 30S shoulder rotation and B8 disruption in the mechanism of decoding. Recent crystallographic data have revealed that mutation G299A in helix h12 allosterically promotes B8 disruption, raising the question of whether G299A and/or other ram mutations act mainly via B8. Here, we compared the effects of each of several ram mutations in the absence and presence of mutation h8Delta2, which effectively takes out bridge B8. The data obtained suggest that a subset of mutations including G299A act in part via B8 but predominantly through another mechanism. We also found that G299A in h12 and G347U in h14 each stabilize tRNA in the A site. Collectively, these data support a model in which rearrangement of the 30S A site, inward shoulder rotation, and bridge B8 disruption are loosely coupled events, all of which promote progression along the productive pathway toward peptide bond formation. PMID- 26873599 TI - The in vivo dynamics of TCERG1, a factor that couples transcriptional elongation with splicing. AB - Coupling between transcription and RNA processing is key for gene regulation. Using live-cell photobleaching techniques, we investigated the factor TCERG1, which coordinates transcriptional elongation with splicing. We demonstrate that TCERG1 is highly mobile in the nucleoplasm and that this mobility is slightly decreased when it is associated with speckles. Dichloro-1-beta-D ribofuranosylbenzimidazole (DRB) but not alpha-amanitin treatment reduced the mobility of TCERG1, which suggests interaction with paused transcription elongation complexes. We found that TCERG1 mobility is rapid at the transcription site (TS) of a reporter that splices post-transcriptionally and that TCERG1 is recruited to the active TS independent of the CTD of RNAPII, thus excluding phosphorylated CTD as a requirement for recruiting this factor to the TS. Importantly, the mobility of TCERG1 is reduced when the reporter splices cotranscriptionally, which suggests that TCERG1 forms new macromolecular complexes when splicing occurs cotranscriptionally. In this condition, spliceostatin A has no effect, indicating that TCERG1 rapidly binds and dissociates from stalled spliceosomal complexes and that the mobility properties of TCERG1 do not depend on events occurring after the initial spliceosome formation. Taken together, these data suggest that TCERG1 binds independently to elongation and splicing complexes, thus performing their coupling by transient interactions rather than by stable association with one or the other complexes. This finding has conceptual implications for understanding the coupling between transcription and RNA processing. PMID- 26873600 TI - Bacillus subtilis 6S-2 RNA serves as a template for short transcripts in vivo. AB - The global transcriptional regulator 6S RNA is abundant in a broad range of bacteria. The RNA competes with DNA promoters for binding to the housekeeping RNA polymerase (RNAP) holoenzyme. When bound to RNAP, 6S RNA serves as a transcription template for RNAP in an RNA-dependent RNA polymerization reaction. The resulting short RNA transcripts (so-called product RNAs = pRNAs) can induce a stable structural rearrangement of 6S RNA when reaching a certain length. This rearrangement leads to the release of RNAP and thus the recovery of transcription at DNA promoters. While most bacteria express a single 6S RNA, some harbor a second 6S RNA homolog (termed 6S-2 RNA in Bacillus subtilis). Bacillus subtilis 6S-2 RNA was recently shown to exhibit essentially all hallmark features of a bona fide 6S RNA in vitro, but evidence for the synthesis of 6S-2 RNA-derived pRNAs in vivo has been lacking so far. This raised the question of whether the block of RNAP by 6S-2 RNA might be lifted by a mechanism other than pRNA synthesis. However, here we demonstrate that 6S-2 RNA is able to serve as a template for pRNA synthesis in vivo. We verify this finding by using three independent approaches including a novel primer extension assay. Thus, we demonstrate the first example of an organism that expresses two distinct 6S RNAs that both exhibit all mechanistic features defined for this type of regulatory RNA. PMID- 26873601 TI - Comparison of acyclovir and famciclovir for the treatment of Bell's palsy. AB - The relative effectiveness of acyclovir and famciclovir in the treatment of Bell's palsy is unclear. This study therefore compared recovery outcomes in patients with Bell's palsy treated with acyclovir and famciclovir. The study cohort consisted of patients with facial palsy who visited the outpatient clinic between January 2006 and January 2014. Patients were treated with prednisolone plus either acyclovir (n = 457) or famciclovir (n = 245). Patient outcomes were measured using the House-Brackmann scale according to initial severity of disease and underlying disease. The overall recovery rate tended to be higher in the famciclovir than in the acyclovir group. The rate of recovery in patients with initially severe facial palsy (grades V and VI) was significantly higher in the famciclovir than in the acyclovir group (p = 0.01), whereas the rates of recovery in patients with initially moderate palsy (grade III-IV) were similar in the two groups. The overall recovery rates in patients without hypertension or diabetes mellitus were higher in the famciclovir than in the acyclovir group, but the difference was not statistically significant. Treatment with steroid plus famciclovir was more effective than treatment with steroid plus acyclovir in patients with severe facial palsy. Famciclovir may be the antiviral agent of choice in the treatment of patients with severe facial palsy. PMID- 26873602 TI - The clinical significance of small subarachnoid hemorrhages. AB - With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests that patients may not require as aggressive monitoring as is currently provided for those with tSAH. PMID- 26873603 TI - CT imaging signs of surgically proven bowel trauma. AB - The objective of this study was to determine the incidence and interobserver agreement of individual CT findings as well as the bowel injury prediction score (BIPS) in surgically proven bowel injury after blunt abdominal trauma. This HIPAA compliant retrospective study was IRB approved and consent was waived. All patients 14 years or older who sustained surgically proven bowel injury after blunt abdominal trauma between 1/1/2004 and 6/30/2015 were included. Admission trauma MDCT scans were independently interpreted by two abdominal fellowship trained radiologists who recorded the following CT findings: intraperitoneal fluid, mesenteric hematoma/fat stranding, bowel wall thickening/hematoma, active intravenous contrast extravasation, free intraperitoneal air, bowel wall discontinuity, and focal bowel hypoenhancement. Subsequently, the electronic medical records of the included patients, admission abdominal physical exam results, admission white blood cell count, and findings at exploratory laparotomy of the included patients were recorded. Thirty-three patients met the inclusion criteria. The incidence and interobserver agreement of the CT findings were as follows: intraperitoneal fluid 93.9 %, kappa = 0.784 (good); mesenteric hematoma/fat stranding 84.8 %, kappa = 0.718 (good); bowel wall thickening/hematoma 42.4 %, kappa = 0.491 (moderate); active IV contrast extravasation 36.3 %, kappa = 1.00 (perfect); free intraperitoneal air 21.2 %, kappa = 0.904 (very good), bowel wall discontinuity 6.1 %, kappa = 1.00 (perfect); and focal bowel hypoenhancement 6.1 %, kappa = 0.468 (moderate). An absence of the specified CT findings was encountered in 9.1 % with surgically proven bowel injuries (kappa = 1.00, perfect). In our study, 9/16 patients or 56.3 % had a bowel injury prediction score (BIPS) of 2 or more as defined by McNutt et al. (J Trauma Acute Care Surg 78(1):105-111, 2014). The presence of intraperitoneal fluid and mesenteric hematoma/fat stranding are the most common CT findings in bowel injuries proven at laparotomy. A small percentage of patients have no abnormal CT findings. This grading system did not prove to be useful in our study likely due to our inherently small patient population; however, the use of BIPS deserves further investigation as it may help in identifying blunt bowel and mesenteric injury patients with often subtle or nonspecific CT findings. PMID- 26873605 TI - Erratum to: Herbivory strongly influences among-population variation in reproductive output of Lythrum salicaria in its native range. PMID- 26873604 TI - Who explicitly requests the ordering of computed tomography for emergency department patients? A multicenter prospective study. AB - Emergency department (ED) computed tomography (CT) use has increased substantially in recent years, resulting in increased radiation exposure for patients. Few studies have assessed which parties contribute to CT ordering in the ED. The objective of this study was to determine the proportion of CT scans ordered due to explicit requests by various stakeholders in ED patient care. This is a prospective, observational study performed at three university hospital EDs. CT scans ordered during research assistant hours were eligible for inclusion. Attending emergency physicians (EPs) completed standardized data forms to indicate all parties who had explicitly requested that a specific CT be performed. Forms were completed before the CT results were known in order to minimize bias. Data were obtained from 77 EPs regarding 944 CTs. The parties most frequently requesting CTs were attending EPs (82.0 %, 95 % CI 79.4-84.3), resident physicians (28.6 %, 95 % CI 25.8-31.6), consulting physicians (24.4 %, 95 % CI 21.7-27.2), and admitting physicians (3.9 %, 95 % CI 2.9-5.4). In the 168 instances in which the attending EP did not explicitly request the CT, requests most commonly came from consulting physicians (51.2 %, 95 % CI 43.7-58.6), resident physicians in the ED (39.9 %, 95 % CI 32.8-47.4), and admitting physicians (8.9 %, 95 % CI 5.5-14.2). EPs were the sole party requesting CT in 46.2 % of cases while multiple parties were involved in 39.0 %. Patients, families, and radiologists were uncommon sources of such requests. Emergency physicians requested the majority of CTs, though nearly 20 % were actually not desired by them. Admitting, consulting, and resident physicians in the ED were important contributors to CT utilization. PMID- 26873606 TI - The relative influences of climate and competition on tree growth along montane ecotones in the Rocky Mountains. AB - Distribution shifts of tree species are likely to be highly dependent upon population performance at distribution edges. Understanding the drivers of aspects of performance, such as growth, at distribution edges is thus crucial to accurately predicting responses of tree species to climate change. Here, we use a Bayesian model and sensitivity analysis to partition the effects of climate and crowding, as a metric of competition, on radial growth of three dominant conifer species along montane ecotones in the Rocky Mountains. These ecotones represent upper and lower distribution edges of two species, and span the distribution interior of the third species. Our results indicate a greater influence of climate (i.e., temperature and precipitation) than crowding on radial growth. Competition importance appears to increase towards regions of more favorable growing conditions, and precise responses to crowding and climate vary across species. Overall, our results suggest that climate will likely be the most important determinant of changes in tree growth at distribution edges of these montane conifers in the future. PMID- 26873607 TI - Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties. AB - It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health. PMID- 26873608 TI - Synthesis and characterization of in situ forming anionic hydrogel as vitreous substitutes. AB - The natural vitreous is a biological hydrogel consisting primarily of a collagen and anionic hyaluronate. It is surgically removed in many ocular diseases and replaced with fluids, gases, or silicone oils. We have been interested in developing synthetic hydrogels as vitreous substitutes. In this study, we combined the stiffness and hydrophobicity of polymethacrylamide (PMAM) and the anionic nature of polymethacrylate (PMAA) to make copolymers that would mimic the natural vitreous. We used bis-methacryloyl cystamine (BMAC) to introduce thiol groups for reversible crosslink. The Mn of copolymers ranged from ~100 k to ~200 k Da (polydisperisty index of 1.47-2.63) and their composition as determined by titration, 1 H NMR and disulfide test were close to the feed ratio. The reactivities of monomers were as follows: MAM > MAA ~ BMAC. Copolymers with higher MAA contents gelled faster, swelled more, and had higher storage modulus (1.5 to 100 Pa) comparable to that of the natural vitreous. We evaluated the biocompatibility of copolymers by electric cell-substrate impedance sensing (ECIS) using human retinal pigment epithelial cells, primary porcine retinal pigmented epithelial cells, human microvascular endothelial cells adult dermis, and a fibroblast line 3T3. The biocompatibility decreases as the content of BMAC increases. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 977-988, 2017. PMID- 26873610 TI - MSF accuses Pfizer of misleading advertising. PMID- 26873609 TI - Development of the Sensory Hypersensitivity Scale (SHS): a self-report tool for assessing sensitivity to sensory stimuli. AB - Sensory hypersensitivity is one manifestation of the central sensitization that may underlie conditions such as fibromyalgia and chronic fatigue syndrome. We conducted five studies designed to develop and validate the Sensory Hypersensitive Scale (SHS); a 25-item self-report measure of sensory hypersensitivity. The SHS assesses both general sensitivity and modality-specific sensitivity (e.g. touch, taste, and hearing). 1202 participants (157 individuals with chronic pain) completed the SHS, which demonstrated an adequate overall internal reliability (Cronbach's alpha) of 0.81, suggesting the tool can be used as a cross-modality assessment of sensitivity. SHS scores demonstrated only modest correlations (Pearson's r) with depressive symptoms (0.19) and anxiety (0.28), suggesting a low level of overlap with psychiatric complaints. Overall SHS scores showed significant but relatively modest correlations (Pearson's r) with three measures of sensory testing: cold pain tolerance (-0.34); heat pain tolerance (-0.285); heat pain threshold (-0.271). Women reported significantly higher scores on the SHS than did men, although gender-based differences were small. In a chronic pain sample, individuals with fibromyalgia syndrome demonstrated significantly higher SHS scores than did individuals with osteoarthritis or back pain. The SHS appears suitable as a screening measure for sensory hypersensitivity, though additional research is warranted to determine its suitability as a proxy for central sensitization. PMID- 26873612 TI - Size and demography pattern of the domestic dog population in Bhutan: Implications for dog population management and disease control. AB - Understanding the demography of domestic dogs is essential to plan the dog population management and rabies control program. In this study, we estimated the owned and stray dog population and the proportion of owned dogs that are free roaming in Bhutan. For this, a cross-sectional household surveys were conducted in six districts (both urban and rural areas) and two border towns in southern Bhutan. The population estimation was done by extrapolation of the mean number of dogs per household and dogs per person, whilst mark-resight survey was conducted to estimate the proportion of owned dogs that were free-roaming. A total of 1,301 (rural:585; urban:716) respondents (one per household) were interviewed of which 173 households (24.4%) in urban areas owned 237 dogs whilst 238 households (40.8%) in rural areas owned 353 dogs. The mean number of dogs per dog owning household was estimated to be 1.44 (urban:1.37 dogs; rural:1.48 dogs) and dogs per household was estimated to be 0.45 (urban:0.33; rural:0.60). The dog: human ratio was 1:16.30 (0.06 dogs per person) in urban areas and 1:8.43 (0.12 dogs per person) in rural areas. The total owned dog population based on the mean number of dogs per household and dogs per person were estimated to be 65,312 and 71,245 in the country, respectively. The male: female ratio of the owned dog was 1.31:1 in urban areas and 2.05:1 in rural areas. Majority of the dogs were local non descript breeds in both urban (60.8%) and rural (78%) areas, and the most common source was acquisition from friends or family (44.7%). The stray dog population in Bhutan was estimated to be 48,379 (urban:22,772; rural:25,607). Of the total estimated owned dog population in the two border towns, the proportion that were found free-roaming was estimated to be 31%. The different dog population estimation methods were compared and discussed in this paper. This study generated baseline data on the demographic patterns of the owned and stray dogs in Bhutan which will be useful for planning and monitoring dog population management and rabies control program in the country. PMID- 26873611 TI - A Prospective Longitudinal Study of Mental Health Symptoms Among Perinatally HIV Infected and HIV-Exposed but Uninfected Urban Youths. AB - PURPOSE: Significant gaps persist in our understanding of the etiological factors that shape the progression of mental health symptoms (MHS) among perinatally HIV infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youths. This study sought to assess the changes in MHS among PHIV+ and PHEU youths as they transition through adolescence and to identify the associated psychosocial factors. METHODS: Data were drawn from a longitudinal study of 166 PHIV+ and 114 PHEU youths (49% male, ages 9-16 years at baseline) in New York City. Individual interviews were administered at baseline and subsequently over a 5-year period. MHS were assessed using the youth version of the Diagnostic Interview Schedule for Children. Predictive growth curve analyses were conducted to assess longitudinal changes in MHS and identify the relevant factors. Level I predictors included: time, major life events, household poverty, caregiver mental health, and neighborhood stressors. Level II predictors included youths' sociodemographic characteristics (e.g., age, gender, HIV status) and baseline future orientation scores. RESULTS: The changes in youths' MHS followed a quadratic growth curve and were positively associated with the number of major negative life events and neighborhood stressors experienced. Youths' HIV status, household poverty, and caregiver mental health were not significantly associated with youths' MHS. CONCLUSIONS: Findings suggest that irrespective of youths' HIV status, major life events and neighborhood stressors increase MHS among PHIV+ and PHEU youths. There is a need for interventions to reduce the impact of stressors on the mental well being of PHIV+ and PHEU youths. PMID- 26873613 TI - "Care or control?": a qualitative study of staff experiences with outpatient commitment orders. AB - PURPOSE: Outpatient commitment orders are being increasingly used in many countries to ensure follow-up care of people with psychotic disorders after discharge from hospital. Several studies have examined outpatient commitment in relation to use of health care services, but there have been fewer studies of health professionals' experiences with the scheme. The purpose of this study was to examine health professionals' experiences with patients subject to outpatient commitment. METHODS: This was a focus group study using a descriptive and exploratory approach. The study was based on three focus group interviews with a total of 22 participants. Data were analysed using qualitative content analysis. RESULTS: The study showed that health professionals had a positive attitude towards outpatient commitment and considered it necessary for patients with psychosis who lacked insight and did not collaborate on treatment. At the same time their attention to patients' lack of insight could lead to a paternalistic approach more than measures to enhance patient autonomy. This challenged their therapeutic relationship with the patient. CONCLUSION: Health professionals found it difficult to combine control with therapeutic care, but gave greater emphasis to patients' need for treatment and continuity of care than to their autonomy. This dilemma indicates a need to discuss whether increased attention to patients' autonomy rather than insight into their illness would improve treatment cooperation and reduce the use of coercion. PMID- 26873614 TI - Perceived ethnic discrimination and depressive symptoms: the buffering effects of ethnic identity, religion and ethnic social network. AB - PURPOSE: Perceived ethnic discrimination (PED) is positively associated with depressive symptoms in ethnic minority groups in Western countries. Psychosocial factors may buffer against the health impact of PED, but evidence is lacking from Europe. We assessed whether ethnic identity, religion, and ethnic social network act as buffers in different ethnic minority groups in Amsterdam, the Netherlands. METHODS: Baseline data were used from the HEalthy Living In a Urban Setting study collected from January 2011 to June 2014. The random sample included 2501 South Asian Surinamese, 2292 African Surinamese, 1877 Ghanaians, 2626 Turks, and 2484 Moroccans aged 18-70 years. Depressive symptoms were assessed using the Patient Health Questionnaire-9. PED was measured with the Everyday Discrimination Scale. Ethnic identity was assessed using the Psychological Acculturation Scale. Practicing religion was determined. Ethnic social network was assessed with the number of same-ethnic friends and amount of leisure time spent with same-ethnic people. RESULTS: PED was positively associated with depressive symptoms in all groups. The association was weaker among (a) those with strong ethnic identity in African Surinamese and Ghanaians, (b) those practicing religion among African Surinamese and Moroccans, (c) those with many same-ethnic friends in South-Asian Surinamese, Ghanaians, and Turks, and (d) those who spend leisure time with same ethnic people among African Surinamese and Turks. CONCLUSIONS: Ethnic identity, religion, and ethnic social network weakened the association between PED and depressive symptoms, but the effects differed by ethnic minority group. These findings suggest that ethnic minority groups employ different resources to cope with PED. PMID- 26873615 TI - Experience of stigma in private life of relatives of people diagnosed with schizophrenia in the Republic of Belarus. AB - PURPOSE: Family stigma constitutes a major problem in schizophrenia worldwide. Data on first-hand experience of stigma in families is necessary for planning and implementing interventions to reduce its burden. The aim of the study was to investigate the experience of stigma among relatives of persons with schizophrenia in Belarus. METHODS: Qualitative research methods, such as the thematic analysis of in-depth semi-structured interviews with 20 relatives of people diagnosed with schizophrenia, were used. Experience of discrimination, strategies used to cope with it, and requests for interventions were investigated. RESULTS: The most salient themes in experience of stigma in the private domain of life elicited in the narratives included anticipated stigma and dissolution of families. The experience of stigma was associated with burdensome feelings of guilt, tiredness and loneliness, together with fear and anxiety due to uncertainty in the future and sorrow because of frustrated hopes in past. Analysis of the strategies used to overcome the difficulties revealed concealment and "life behind closed doors", avoidance of the rest of the family, taking full responsibility and sacrificing one's personal life. CONCLUSION: To reduce the burden of stigma in the private life of the family members of people living with schizophrenia in Belarus, important steps should be taken to promote the empowerment of families including: reforming mental health services; provision of better access to information; family support services, community care; development of family organisations; assistance in communication, re socialisation and independent living for people diagnosed with schizophrenia. PMID- 26873617 TI - Incomplete penetrance of biallelic ALDH1A3 mutations. AB - The formation of a properly shaped eye is a complex developmental event that requires the coordination of many induction processes and differentiation pathways. Microphthalmia and anophthalmia (MA) represent the most severe defects that can affect the ocular globe during embryonic development. When genetic, these ocular disorders exhibit large genetic heterogeneity and extreme variable expressivity. Around 20 monogenic diseases are known to be associated with MA as main phenotype and the penetrance of mutations is usually full in the patients. Some of these genes encode proteins involved in the vitamin A pathway, tightly regulated during eye development. One of those retinoic acid synthesis genes is ALDH1A3 and biallelic mutations in that gene have been recently found to lead to MA phenotype in patients. Interestingly, we report here the lack of ocular defect in a girl carrying the same homozygous mutation in the ALDH1A3 gene than the affected members of her family. Thus, this report brings new information for the phenotype-genotype correlation of ALDH1A3 mutations and raises important questions, especially in terms of genetic counselling given to the patients and their families. Furthermore, these data contribute to the more general understanding that we have for the complex genetic inheritance of these MA phenotypes. PMID- 26873616 TI - Kin Discrimination in Protists: From Many Cells to Single Cells and Backwards. AB - During four decades (1960-1990s), the conceptualization and experimental design of studies in kin recognition relied on work with multicellular eukaryotes, particularly Unikonta (including invertebrates and vertebrates) and some Bikonta (including plants). This pioneering research had an animal behavior approach. During the 2000s, work on taxa-, clone- and kin-discrimination and recognition in protists produced genetic and molecular evidence that unicellular organisms (e.g. Saccharomyces, Dictyostelium, Polysphondylium, Tetrahymena, Entamoeba and Plasmodium) could distinguish between same (self or clone) and different (diverse clones), as well as among conspecifics of close or distant genetic relatedness. Here, we discuss some of the research on the genetics of kin discrimination/recognition and highlight the scientific progress made by switching emphasis from investigating multicellular to unicellular systems (and backwards). We document how studies with protists are helping us to understand the microscopic, cellular origins and evolution of the mechanisms of kin discrimination/recognition and their significance for the advent of multicellularity. We emphasize that because protists are among the most ancient organisms on Earth, belong to multiple taxonomic groups and occupy all environments, they can be central to reexamining traditional hypotheses in the field of kin recognition, reformulating concepts, and generating new knowledge. PMID- 26873618 TI - Maternally inherited autosomal dominant intellectual disability caused by 16p13.3 microduplication. AB - A 16p13.3 duplication syndrome has been recently suggested to be a novel recognizable syndrome as a reciprocal microduplication disease of Rubinstein Taybi syndrome. The CREBBP gene is believed to be the dosage-sensitive critical gene responsible for the reciprocal duplication and deletion syndrome. Descriptions so far have been de novo. Here, we report a very rare case of a maternally inherited a -1 Mb sized duplication on 16p13.3 identified by SNP array testing. The patient showed moderate intellectual disability, normal growth, and characteristic facial features. The patient's mother also had mild intellectual disability, normal growth, camptodactyly, proximally implanted small thumbs, and distinctive facial features. The study provides additional information that furthers the understanding and delineation of 16p13.3 duplication syndrome. PMID- 26873619 TI - The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2015 edition. PMID- 26873620 TI - Absence of K-Ras Reduces Proliferation and Migration But Increases Extracellular Matrix Synthesis in Fibroblasts. AB - The involvement of Ras-GTPases in the development of renal fibrosis has been addressed in the last decade. We have previously shown that H- and N-Ras isoforms participate in the regulation of fibrosis. Herein, we assessed the role of K-Ras in cellular processes involved in the development of fibrosis: proliferation, migration, and extracellular matrix (ECM) proteins synthesis. K-Ras knockout (KO) mouse embryonic fibroblasts (K-ras(-/-) ) stimulated with transforming growth factor-beta1 (TGF-beta1) exhibited reduced proliferation and impaired mobility than wild-type fibroblasts. Moreover, an increase on ECM production was observed in K-Ras KO fibroblasts in basal conditions. The absence of K-Ras was accompanied by reduced Ras activation and ERK phosphorylation, and increased AKT phosphorylation, but no differences were observed in TGF-beta1-induced Smad signaling. The MEK inhibitor U0126 decreased cell proliferation independently of the presence of K-ras but reduced migration and ECM proteins expression only in wild-type fibroblasts, while the PI3K-AKT inhibitor LY294002 decreased cell proliferation, migration, and ECM synthesis in both types of fibroblasts. Thus, our data unveil that K-Ras and its downstream effector pathways distinctively regulate key biological processes in the development of fibrosis. Moreover, we show that K-Ras may be a crucial mediator in TGF-beta1-mediated effects in this cell type. J. Cell. Physiol. 231: 2224-2235, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26873621 TI - Prevalence and management of hypertensive patients in clinical practice: Cross sectional registry in five countries outside the European Union. AB - Inadequate blood pressure (BP) control may be linked with poor adherence to guidelines by the treating physician. This study aimed at assessing the rates of controlled hypertension as per the 2009 Reappraisal of the 2007 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines in 2185 hypertensive adults across five countries (Algeria, Pakistan, Ukraine, Egypt and Venezuela). The rates of controlled hypertension according to physician perception, type of therapy and risk factors were evaluated. Overall, 40% of patients had controlled hypertension according to the guidelines. A marked divergence in the rates of controlled hypertension as assessed by physicians and guidelines was observed (72% vs 40%). The presence of high/very high risks was linked to poor BP control. High salt intake [29%; odds ratio (OR) 9.94, 95% confidence interval (CI) 6.72;14.69], treatment non-adherence (27%; OR 7.32, 95% CI 4.82;11.13), lack of understanding of the treatment's importance (25%; OR 4.95, 95% CI 3.16;7.75), comorbidity (13%) and depression (9%; OR 10.50, 95% CI 5.37;20.54) were major reasons for not achieving hypertension control. Addition of another drug was the most frequent medication change prescribed. Poor rates of BP control warrant repeated promotion of guidelines while identifying potential contributing factors and implementing strategies that re-establish BP control. PMID- 26873622 TI - Peter Meredith. PMID- 26873623 TI - Bimatoprost solution 0.03% topical application to the eyelid margin for the treatment of eyelash hypotrichosis. PMID- 26873624 TI - Tagetes lucida Cav.: Ethnobotany, phytochemistry and pharmacology of its tranquilizing properties. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Morelos State is one of the most important regions of Mexico where several plant species are used in traditional medicine to influence central nervous system (CNS) activity; for example Tagetes lucida Cav. AIM OF THE STUDY: To investigate the ethnobotany, phytochemistry and pharmacology of the tranquilizing properties of T. lucida aerial parts. MATERIAL AND METHODS: Data on the medicinal uses of T. lucida were explored by interviewing healers and merchants of local markets in different regions of Morelos State by using a questionnaire. Anxiolytic and/or sedative-like responses of the T. lucida were investigated in experimental models in mice such as: open-field, exploration cylinder, hole-board, plus-maze, and the barbituric-induced hypnosis potentiation. The possible mechanism of action was explored in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.) antagonists. A feasible active compound was isolated and identified by using conventional chromatography, including UHPLC and MS (DART) [M+H]+ techniques. RESULTS: Interviews of healers and merchants from ten local regions of Morelos State showed that they recommended T. lucida as infusion and as tincture for several culture-bound syndromes associated with the CNS. Anxiolytic and sedative-like activities of polar extracts were corroborated in the experimental models; these effects were inhibited in the presence of 5-HT1A and GABA/BDZ receptor antagonists. Dimethylfraxetin was identified as one possible active compound. CONCLUSIONS: The results support the anxiolytic and sedative-like properties of T. lucida in traditional medicine by involving serotonergic and GABAergic neurotransmission and coumarinic constituents. PMID- 26873626 TI - Imaging of focal calvarial lesions. AB - Focal calvarial lesions may present as a visible, palpable, or symptomatic lump; however, with increasing use of cross-sectional imaging they are often encountered as an incidental finding. Knowledge of the possible disease entities along with a structured approach to imaging is required to suggest an appropriate diagnosis and assist in management planning. Abnormalities range from common neoplastic lesions to rarer congenital conditions, benign pathologies, and calvarial defects that can mimic lesions. The aim of this article is to demonstrate the salient imaging features that may help to limit the differential diagnosis of a focal calvarial lesion. PMID- 26873627 TI - Correlation between vascular endothelial growth factor and quantitative dual energy spectral CT in non-small-cell lung cancer. AB - AIM: To explore the correlation between the expression level of vascular endothelial growth factor (VEGF) in non-small-cell lung cancer (NSCLC) tissue and quantitative parameters of spectral computed tomography (CT) imaging. MATERIALS AND METHODS: Forty-eight patients with NSCLC underwent a spectral CT imaging protocol before surgical tumour resection. The repetition of iodine concentration, water concentration, and CT values at 40 keV in the region of interest were measured. The slopes of spectral attenuation curves (lambdaHU) in the region were also calculated. The level of VEGF expression in the tumour tissue was measured using an immunohistochemical method (MaxVision method). The quantitative parameters of spectral CT imaging were compared among different levels of VEGF expression using one-way analysis of variance (ANOVA) and least significant difference (SLD) test. The correlation between VEGF expression and spectral CT imaging was estimated through Spearman's rank correlation analysis. RESULTS: There were significant differences in iodine concentrations, lambdaHU, and CT values at 40 KeV in NSCLC between the groups showing negative and moderately positive expression of VEGF (p=0.001, 0.000, and 0.001, respectively) as well as between those showing mildly and moderately positive expression of VEGF (p=0.047, 0.005, and 0.002, respectively). In addition, all of the iodine concentrations, lambdaHU values, and CT values at 40 KeV displayed a significant and positive correlation with the level of VEGF expression (r=0.413, 0.458, and 0.393, respectively, p<0.05). CONCLUSIONS: Quantitative parameters of spectral CT imaging may be helpful for evaluating the status of angiogenesis in NSCLC. PMID- 26873628 TI - Adhesion molecules expression in CLL: Potential impact on clinical and hematological parameters. AB - BACKGROUND: B-cell chronic lymphocytic leukemia (CLL) is marked by the accumulation of CD5+ B lymphocytes within the blood, bone marrow (BM), and secondary lymphoid tissues. Abnormalities in the expression and function of cell adhesion molecules may account for the patterns of intra-nodal growth and hematogenous spread of the malignant cells. Chemokines and integrin-mediated adhesion and trans-endothelial migration (TEM) are central aspects in trafficking and retention of hematopoietic cells in the BM and lymphoid organs. AIM OF THE WORK: This work was conducted to study adhesion molecules status in CLL and its potential impact on both hematological and clinical parameters. PATIENTS AND METHODS: The study included 78 newly diagnosed CLL patients. Immunophenotyping was performed on peripheral blood using the chronic lymphoid panel. Adhesion molecules (CD11a, CD11b, CD49d, CD49C, CD29 and CD38) were tested using monoclonal antibodies and analyzed by Flow Cytometry. RESULTS: Positive correlation was encountered between adhesion molecules: CD38 with CD49d (r=0.25, p=0.028), CD11a with CD11b, CD49d and CD29 (r=0.394, p=0.001; r=0.441, p=<0.01 and r=0.446, p<0.01 respectively) and CD29 with CD49c and CD49d (r=0.437, p<0.01; r=0.674, p<0.01 respectively). CD49c showed negative correlation with Rai staging (r=-0.269, p=0.033). CD11a and CD29 showed a significant relation with splenomegaly (p=0.04 and 0.03 respectively) and CD49d showed a significant relation with lymphadenopathy (p=0.02). CONCLUSION: The level of different adhesion molecules expression in CLL is apparently reflected on the potential migratory behavior of the leukemic cells to different organs. PMID- 26873630 TI - A domestication related mutation in the thyroid stimulating hormone receptor gene (TSHR) modulates photoperiodic response and reproduction in chickens. AB - The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a "domestication locus" in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects of a mutation in the gene on several domestication related traits, indicate that the gene has been important for chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We used birds from an advanced intercross line between ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects of the mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wild type allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling for background variation in the rest of the genome. TSHR gene expression in brain was significantly lower in both d/d females and males and d/d females showed a faster onset of egg laying at sexual maturity than w/w. Furthermore, d/d males showed a reduced testicular size response to decreased day length, and lower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under natural short day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3 expression compared to Red Junglefowl females kept under similar conditions. Our study indicates that the TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction, a typical domestication feature, and may therefore have been important for chicken domestication. PMID- 26873629 TI - RNAi-mediated Ghrelin affects gastric H(+)-K(+)-ATPase activity and expression of GOAT-Ghrelin system in vitro. AB - Ghrelin has been implicated in the regulation of gastric functional development, and its physiological functions are mediated by Ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this polypeptide hormone. However, whether and how ghrelin gene silencing may modify gastric acid secretion and GOAT-Ghrelin system is yet to be explored. The study was performed in gastric mucosal cells from weanling piglets in vitro. We evaluated the effect of ghrelin on gastric acid secretion, gene expression of GOAT and ghrelin as well as ghrelin levels by RNA interference assay. shGhrelin triggered the down-regulation of ghrelin mRNA expression (P<0.05) via an RNAi mechanism, as observed by real-time RT-PCR. In addition, shGhrelin showed reduced total ghrelin production and secretion (P<0.05) using ELISA in vitro. We also detected that GOAT mRNA expression was reduced in shGhrelin group (P<0.05), compared with control groups. In accordance with the GOAT expression, acylated ghrelin production and secretion were reduced in gastric mucosal cells and culture medium (P<0.05). Silencing of ghrelin gene achieved by RNAi-mediation inhibited the activity of H(+)-K(+) ATPase and pepsin (P<0.05) in gastric mucosal cells. These results indicated that RNAi of Ghrelin gene inhibited the gastric acid secretion with decreased GOAT mRNA and acylated Ghrelin in gastric mucosal cells. PMID- 26873631 TI - AMPK is involved in the differential neonatal performance of chicks hatching at different time. AB - We have recently reported that the hatching time may be in relation to the distinct neonatal performance of female chicks. The present study was aimed to investigate the potential involvement of AMPK, an energy sensor which plays a pivotal role in energy homeostasis, in the distinct performance of the spread of hatching time model. As a result, hypothalamic AMPKalpha1 isoform gene expression was significantly higher in the late hatcher as compared to that of their early counterparts, whereas the total and phosphorylated levels of AMPKalpha subunit did not differ between the three hatchers. The hypothalamic orexigenic NPY and AgRP mRNA levels were higher in the late hatchers as compared to the early, and that of the middle hatchers was at an intermediate level. However, the anorexigenic POMC and CRH was also higher expressed in the late hatchers as compared to the early hatchers. In the liver, AMPKalpha2 mRNA level and the phosphorylation ratio of AMPKalpha was significantly lower in the late hatchers, as compared to their early counterparts. The hepatic phosphorylated GS levels of the late and middle hatchers were lower than that of their early counterparts. The expression of hepatic FTO gene of the late hatchers was significantly higher than that of their early and middle counterparts. Taken together, AMPK may play a significant role in the different neonatal performance of the spread of hatching time model. The central and peripheral AMPK in late hatchers exhibited a pattern of higher energy intake and lower energy expenditure, which resulted in a faster post-hatch growth. PMID- 26873625 TI - Actin dynamics and cofilin-actin rods in alzheimer disease. AB - Cytoskeletal abnormalities and synaptic loss, typical of both familial and sporadic Alzheimer disease (AD), are induced by diverse stresses such as neuroinflammation, oxidative stress, and energetic stress, each of which may be initiated or enhanced by proinflammatory cytokines or amyloid-beta (Abeta) peptides. Extracellular Abeta-containing plaques and intracellular phospho-tau containing neurofibrillary tangles are postmortem pathologies required to confirm AD and have been the focus of most studies. However, AD brain, but not normal brain, also have increased levels of cytoplasmic rod-shaped bundles of filaments composed of ADF/cofilin-actin in a 1:1 complex (rods). Cofilin, the major ADF/cofilin isoform in mammalian neurons, severs actin filaments at low cofilin/actin ratios and stabilizes filaments at high cofilin/actin ratios. It binds cooperatively to ADP-actin subunits in F-actin. Cofilin is activated by dephosphorylation and may be oxidized in stressed neurons to form disulfide linked dimers, required for bundling cofilin-actin filaments into stable rods. Rods form within neurites causing synaptic dysfunction by sequestering cofilin, disrupting normal actin dynamics, blocking transport, and exacerbating mitochondrial membrane potential loss. Abeta and proinflammatory cytokines induce rods through a cellular prion protein-dependent activation of NADPH oxidase and production of reactive oxygen species. Here we review recent advances in our understanding of cofilin biochemistry, rod formation, and the development of cognitive deficits. We will then discuss rod formation as a molecular pathway for synapse loss that may be common between all three prominent current AD hypotheses, thus making rods an attractive therapeutic target. (c) 2016 Wiley Periodicals, Inc. PMID- 26873632 TI - Role of aromatase and radial glial cells in neurotoxin-induced dopamine neuron degeneration and regeneration. AB - Radial glial cells (RGCs) in teleost brain are progenitor cells that express aromatase B and produce estrogens. Controversial data suggest that estrogens are critical for brain repair and neurogenesis in teleosts. Using a goldfish model for neurotoxin-induced Parkinson-like syndrome, we investigated the possible roles of RGCs, especially estrogen synthetic function, in the processes underlying dopamine neuron regeneration. The data indicate that dopamine neuron degeneration and aromatase activity inhibition could be respectively achieved in vivo with treatments with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) and fadrozole in female goldfish. The expression of genes in the telencephalon and hypothalamus related to RGC functions including gfap, gdnf and bdnf as well as genes related to mature dopamine neuron functions including th, slc6a3 and pitx3 are under modulation of estrogens. Together these results revealed that the activation of radial glial cells and dopamine neuron recovery after MPTP insult is aromatase-dependent. Findings in this study provide support for the hypothesis that endogenous estrogens are neuroprotective in goldfish. Future studies focus on the molecular pathways for enhancing protective functions of estrogens and understanding global effects of estrogens in the central nervous system. PMID- 26873633 TI - iPLA2beta deficiency attenuates obesity and hepatic steatosis in ob/ob mice through hepatic fatty-acyl phospholipid remodeling. AB - PLA2G6 or GVIA calcium-independent PLA2 (iPLA2beta) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2beta is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2beta-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2beta could regulate obesity and hepatic steatosis in leptin deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARgamma and de novo lipogenesis genes, and the reversal of beta-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2beta deficiency in ob/ob PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2beta deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2beta in severe obesity associated NAFLD. PMID- 26873634 TI - Prednisolone- and sirolimus-eluting stent: Anti-inflammatory approach for inhibiting in-stent restenosis. AB - Glucocorticoids are powerful anti-inflammatory, immunosuppressive, and anti proliferative agents. The aim of this study was to evaluate the effectiveness of a prednisolone- (PDScs) and sirolimus-coated stent (SRLcs) in preventing artery vessel neointimal hyperplasia and inflammatory reactions in vitro and in vivo. PDS, a synthetic glucocorticoid, is a derivative of cortisol, which is used to treat a variety of inflammatory and autoimmune conditions. The stents were fabricated with PDS, SRL, or both agents using a layer-by-layer coating system (designated as PDScs, SRLcs, and PDSRLcs, respectively). The surface morphology of the PDScs showed an evenly dispersed and roughened shape, which was smoothened by the SRL coating. Half of the total drug amounts were released within seven days, followed by an additional release, which continued for up to 28 days. The proliferation of smooth muscle cells was inhibited in the SRLcs group (31.5 +/- 4.08%), and this effect was enhanced by PDS addition (PDSRLcs, 46.8 +/- 8.11%). Consistently, in the animal study, the restenosis rate was inhibited by the SRLcs and PDSRLcs (18.5 +/- 6.23% and 14.5 +/- 3.55%, respectively). Especially, fibrin expression and inflammation were suppressed in the PDS-containing group (PDScs, 0.6 +/- 0.12 and 1.4 +/- 0.33; PDSRLcs, 0.7 +/- 0.48 and 1.7 +/- 0.12, respectively) compared to PDS non-containing groups (BMS, 1.1 +/- 0.12, and 1.8 +/- 0.55; SRLcs, 1.6 +/- 0.32 and 2.0 +/- 0.62, respectively). Moreover, re endothelialization was enhanced in the PDScs group as determined using immunohistochemistry with a cluster of differentiation (CD)-31 antibodies. These results suggest that the inhibitory effect of SRLcs on anti-restenosis can be accelerated by additional coating with PDS, which has promising properties as a bioactive compound with useful anti-inflammatory effects. PMID- 26873636 TI - Yeast Two-Hybrid and One-Hybrid Screenings Identify Regulators of hsp70 Gene Expression. AB - The mammalian stress protein Hsp105beta, which is specifically expressed during mild heat shock and localizes to the nucleus, induces the major stress protein Hsp70. In the present study, we performed yeast two-hybrid and one-hybrid screenings to identify the regulators of Hsp105beta-mediated hsp70 gene expression. Six and two proteins were detected as Hsp105beta- and hsp70 promoter binding proteins, respectively. A luciferase reporter gene assay revealed that hsp70 promoter activation is enhanced by the transcriptional co-activator AF9 and splicing mediator SNRPE, but suppressed by the coiled-coil domain-containing protein CCDC127. Of these proteins, the knockdown of SNRPE suppressed the expression of Hsp70 irrespective of the presence of Hsp105beta, indicating that SNRPE essentially functions as a transcriptional activator of hsp70 gene expression. The overexpression of HSP70 in tumor cells has been associated with cell survival and drug resistance. We here identified novel regulators of Hsp70 expression in stress signaling and also provided important insights into Hsp70 targeted anti-cancer therapy. J. Cell. Biochem. 117: 2109-2117, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26873635 TI - In vitro three-dimensional coculturing poly3-hydroxybutyrate-co-3 hydroxyhexanoate with mouse-induced pluripotent stem cells for myocardial patch application. AB - Identifying a suitable polymeric biomaterial for myocardial patch repair following myocardial infarction, cerebral infarction, and cartilage injury is essential. This study aimed to investigate the effect of the novel polymer material, poly3-hydroxybutyrate-co-3-hydroxyhexanoate, on the adhesion, proliferation, and differentiation of mouse-induced pluripotent stem cells in vitro. Mouse-induced pluripotent stem cells were isolated, expanded, and cultured on either two-dimensional or three-dimensional poly3-hydroxybutyrate-co-3 hydroxyhexanoate films (membranes were perforated to imitate three-dimensional space). Following attachment onto the films, mouse-induced pluripotent stem cell morphology was visualized using scanning electron microscopy. Cell vitality was detected using the Cell Counting Kit-8 assay and cell proliferation was observed using fluorescent 4',6-diamidino-2-phenylindole (DAPI) staining. Mouse-induced pluripotent stem cells were induced into cardiomyocytes by differentiation medium containing vitamin C. A control group in the absence of an inducer was included. Mouse-induced pluripotent stem cell survival and differentiation were observed using immunofluorescence and flow cytometry, respectively. Mouse-induced pluripotent stem cells growth, proliferation, and differentiation were observed on both two-dimensional and three-dimensional poly3-hydroxybutyrate-co-3 hydroxyhexanoate films. Vitamin C markedly improved the efficiency of mouse induced pluripotent stem cells differentiation into cardiomyocytes on poly3 hydroxybutyrate-co-3-hydroxyhexanoate films. Three-dimensional culture was better at promoting mouse-induced pluripotent stem cell proliferation and differentiation compared with two-dimensional culture. PMID- 26873637 TI - Extremity soft tissue sarcoma with multiple primary malignancies--Characteristics and outcome. AB - BACKGROUND: Understanding the incidence and characteristics of multiple primary malignancies (MPM) has implications for guiding appropriate treatment and surveillance of extremity soft tissue sarcoma (STS). OBJECTIVES: We sought to examine the incidence of MPM in STS (MPM-STS), and compare their clinicopathologic characteristics and survival to those with STS only. METHODS: 585 patients who underwent surgery for extremity STS were reviewed. Logistic regression analyses to identify factors contributing to the development of MPMs and a 1:2 matched case-control analysis to compare survival outcome were performed. RESULTS: Of the 585 patients analyzed, 34 (6%) with MPM were identified. On univariate logistic regression analysis, older age (>49 years) at STS diagnosis (p = 0.008) and histologic types of undifferentiated pleomorphic sarcoma or myxofibrosarcoma (p = 0.033) were significant. In multivariate analysis, only older age at STS diagnosis remained significant (OR = 2.5, p = 0.029). Cancer-specific survival of the MPM-STS group was significantly lower than that of the STS-only group (p = 0.031). However, there was no significant difference in STS-specific survival between the two groups (p = 0.208). CONCLUSION: Our study suggests that MPM is not uncommon in extremity STS and older age at STS diagnosis is associated with risk of MPM. Prognosis of STS in the MPM-STS group seems similar to that of the STS-only group. PMID- 26873638 TI - Dissecting the peripheral stalk of the mitochondrial ATP synthase of chlorophycean algae. AB - The algae Chlamydomonas reinhardtii and Polytomella sp., a green and a colorless member of the chlorophycean lineage respectively, exhibit a highly-stable dimeric mitochondrial F1Fo-ATP synthase (complex V), with a molecular mass of 1600 kDa. Polytomella, lacking both chloroplasts and a cell wall, has greatly facilitated the purification of the algal ATP-synthase. Each monomer of the enzyme has 17 polypeptides, eight of which are the conserved, main functional components, and nine polypeptides (Asa1 to Asa9) unique to chlorophycean algae. These atypical subunits form the two robust peripheral stalks observed in the highly-stable dimer of the algal ATP synthase in several electron-microscopy studies. The topological disposition of the components of the enzyme has been addressed with cross-linking experiments in the isolated complex; generation of subcomplexes by limited dissociation of complex V; detection of subunit-subunit interactions using recombinant subunits; in vitro reconstitution of subcomplexes; silencing of the expression of Asa subunits; and modeling of the overall structural features of the complex by EM image reconstruction. Here, we report that the amphipathic polymer Amphipol A8-35 partially dissociates the enzyme, giving rise to two discrete dimeric subcomplexes, whose compositions were characterized. An updated model for the topological disposition of the 17 polypeptides that constitute the algal enzyme is suggested. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26873639 TI - Performance of a scanning mobility particle sizer in measuring diverse types of airborne nanoparticles: Multi-walled carbon nanotubes, welding fumes, and titanium dioxide spray. AB - Direct-reading instruments have been widely used for characterizing airborne nanoparticles in inhalation toxicology and industrial hygiene studies for exposure/risk assessments. Instruments using electrical mobility sizing followed by optical counting, e.g., scanning or sequential mobility particle spectrometers (SMPS), have been considered as the "gold standard" for characterizing nanoparticles. An SMPS has the advantage of rapid response and has been widely used, but there is little information on its performance in assessing the full spectrum of nanoparticles encountered in the workplace. In this study, an SMPS was evaluated for its effectiveness in producing "monodisperse" aerosol and its adequacy in characterizing overall particle size distribution using three test aerosols, each mimicking a unique class of real-life nanoparticles: singlets of nearly spherical titanium dioxide (TiO2), agglomerates of fiber-like multi-walled carbon nanotube (MWCNT), and aggregates that constitutes welding fume (WF). These aerosols were analyzed by SMPS, cascade impactor, and by counting and sizing of discrete particles by scanning and transmission electron microscopy. The effectiveness of the SMPS to produce classified particles (fixed voltage mode) was assessed by examination of the resulting geometric standard deviation (GSD) from the impactor measurement. Results indicated that SMPS performed reasonably well for TiO2 (GSD = 1.3), but not for MWCNT and WF as evidenced by the large GSD values of 1.8 and 1.5, respectively. For overall characterization, results from SMPS (scanning voltage mode) exhibited particle-dependent discrepancies in the size distribution and total number concentration compared to those from microscopic analysis. Further investigation showed that use of a single-stage impactor at the SMPS inlet could distort the size distribution and underestimate the concentration as shown by the SMPS, whereas the presence of vapor molecules or atom clusters in some test aerosols might cause artifacts by counting "phantom particles." Overall, the information obtained from this study will help understand the limitations of the SMPS in measuring nanoparticles so that one can adequately interpret the results for risk assessments and exposure prevention in an occupational or ambient environment. PMID- 26873640 TI - Critical Analysis of the Use of Uroflowmetry for Urethral Stricture Disease Surveillance. AB - OBJECTIVE: To critically evaluate the use of uroflowmetry (UF) in a large urethral stricture disease cohort as a means to monitor for stricture recurrence. MATERIALS AND METHODS: This study included men that underwent anterior urethroplasty and completed a study-specific follow-up protocol. Pre- and postoperative UF studies of men found to have cystoscopic recurrence were compared to UF studies from successful repairs. UF components of interest included maximum flow rate (Qm), average flow rate (Qa), and voided volume, in addition to the novel post-UF calculated value of Qm minus Qa (Qm-Qa). Area under the receiver operating characteristic curves (AUC) of individual UF parameters was compared. RESULTS: Qm-Qa had the highest AUC (0.8295) followed by Qm (0.8241). UF performed significantly better in men <=40 with an AUC of 0.9324 and 0.9224 for Qm-Qa and Qm respectively, as compared to 0.7484 and 0.7661 in men >40. Importantly, of men found to have anatomic recurrences, only 41% had a Qm of <=15 mL/s at time of diagnostic cystoscopy, whereas over 83% were found to have a Qm-Qa of <=10 mL/s. CONCLUSION: Qm rate alone may not be sensitive enough to replace cystoscopy when screening for stricture recurrence in all patients, especially in younger men where baseline flow rates are higher. Qm-Qa is a novel calculated UF measure that appears to be more sensitive than Qm when using UF to screen for recurrence, as it may be a better numerical representation of the shape of the voiding curve. PMID- 26873642 TI - An open-label, single-arm, phase 2 study of the Aurora kinase A inhibitor alisertib in patients with advanced urothelial cancer. AB - BACKGROUND: Progress in developing effective salvage therapies for UC is warranted. Alisertib is an orally available, selective inhibitor of the aurora kinase A. METHODS: A single-group, phase 2 trial was conducted with alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT02109328). The primary endpoint (EP) was RECIST 1.1 objective response-rate (ORR, H0 <= 5%, H1 >= 20%, alpha = 10% and beta = 20%). Eligibility included failure of at least one platinum-based regimen. RESULTS: From 10/2014 to 04/2015, 22 patients were enrolled (20 evaluable for response), 8 (36.4%) in second-line and 14 (63.6 %) beyond the second-line. Eight (36.4%) had an ECOG-performance status 1-2. Two partial responses (PR, ORR: 9.1%), 7 stable disease (SD) and 11 PD were obtained. Median follow-up was 8.3 months (IQR: 7-10.3), 6-month progression-free survival (PFS) was 13.6% (95%CI: 4.8-39.0). Two SD are still receiving treatment after 11.5 and 6.3 months. Median overall survival (OS) was not reached (6-month OS: 59.1%, 95%CI: 41.7-83.7). Hb < 10 g/dl was significantly associated with shorter PFS and OS multivariably (p = 0.031 and p = 0.033). Tissue of the case with 11.5 month SD harbored a missense mutation of mTOR (E1813D), the nonsense mutation Q527STOP of TSC1, HER3 and TAF1L missense mutations. Grade 3-4 adverse events (AE) were: 40.9% mucositis, 36.4% fatigue, 18.2% neutropenia (13.6% febrile neutropenia). There were 2 treatment-related deaths. CONCLUSIONS: The study did not meet the primary EP, yet sustained disease control was obtained in about 14% of patients. The incidence of AE and the issue of patient selection are two major concerns. PMID- 26873641 TI - Pyruvate and Metabolic Flexibility: Illuminating a Path Toward Selective Cancer Therapies. AB - Dysregulated metabolism is an emerging hallmark of cancer, and there is abundant interest in developing therapies to selectively target these aberrant metabolic phenotypes. Sitting at the decision-point between mitochondrial carbohydrate oxidation and aerobic glycolysis (i.e., the 'Warburg effect'), the synthesis and consumption of pyruvate is tightly controlled and is often differentially regulated in cancer cells. This review examines recent efforts toward understanding and targeting mitochondrial pyruvate metabolism, and addresses some of the successes, pitfalls, and significant challenges of metabolic therapy to date. PMID- 26873644 TI - External fixation reconstruction of the residual problems of benign bone tumours. AB - The mechanical features of and biologic response to using distraction osteogenesis with the circular external fixator are the unique aspects of Ilizarov's contribution that allows deformity correction and reconstruction of bone defects. We present a retrospective study of 20 patients who suffered from a variety of benign tumours for which external fixators (EF) were used to treat deformity, bone loss, and limb-length discrepancy. A total of 26 bony segments in twenty patients (10 males, 10 females; mean age 17 years; range 7-58 years) were treated with EF for residual problems from the tumour itself (primary treatment) in 8 patients and for complications related to the primary surgery (secondary treatment) in 12 patients. Histological diagnoses were Ollier's disease (n = 4), Fibrous Dysplasia (n = 5), Congenital multiple exostosis (n = 5), giant cell tumour (n = 2) and one case for chondromyxoid fibroma, desmoid fibroma, chondroma and unicameral bone cyst. Various types of external fixators used to treat these problems. These were Ilizarov, unilateral fixator, multiaxial correction frame (Biomet, Parsippany, NJ), Taylor spatial frame (Memphis, TN) and smart correction multiaxial frame. The mean follow-up time was 69.5 months (range 35-108 months). The mean external fixation time was 159.5 days (range 27-300 days). The mean external fixation index was 67.4 days/cm (12-610) in 26 limbs who underwent distraction osteogenesis. The mean length of distraction was 4.9 cm (range 0.2-14 cm). At final follow-up, all patients had returned to normal activities. Complications were in the form of knee arthrodesis in one patient, pin tract infection in six and residual shortening in eight patients. The use of EF and the principles of distraction osteogenesis, in the management of problems associated with benign bone tumours and related surgery yields successful results especially in young patients. With this approach, the risk for recurrence of shortening and deformity may be minimized with overcorrection or over-lengthening as dictated by preoperative planning. PMID- 26873643 TI - Targeted therapies in gastric cancer treatment: where we are and where we are going. AB - Gastric cancer (GC) is one of the most common malignancies and a major cause of cancer-related deaths worldwide. Its incidence has significantly declined over the last few decades, probably due to the identification of specific etiologic agents such as Helicobacter pylori and other dietary and environmental risk factors. Nevertheless, most of the cases are unfortunately diagnosed at an advanced stage justifying median overall survival rates frequently not exceeding one year. Palliative combination chemotherapy usually represented by a platinum based doublet is the mainstay of treatment in the metastatic setting. Adding a third drug such as an anthracycline or a taxane has been shown to improve response rate and provide limited survival benefits in fit selected patients. Unlike other tumors, the introduction of molecularly targeted drugs in the medical armamentarium for GC is relatively recent with trastuzumab and ultimately ramucirumab constituting the only agents approved to date. Recent advances in the understanding of GC biology have led to the development of novel targeted therapies holding the promise to further improve treatment outcomes. The aim of this paper is to review the main available data coming from clinical trials of targeted drugs and to describe some of the most interesting molecules in clinical development in GC. These include drugs targeting EGFR, angiogenesis, c-MET, FGFR2, mTOR and immune checkpoints. PMID- 26873645 TI - A guide to treating gait impairment with prolonged-release fampridine (Fampyra(r)) in patients with multiple sclerosis. AB - INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS. PMID- 26873646 TI - Comments on the review article "Cerebral radiation necrosis: Diagnostic challenge and clinical management". PMID- 26873647 TI - Systemic mechanisms and effects of ionizing radiation: A new 'old' paradigm of how the bystanders and distant can become the players. AB - Exposure of cells to any form of ionizing radiation (IR) is expected to induce a variety of DNA lesions, including double strand breaks (DSBs), single strand breaks (SSBs) and oxidized bases, as well as loss of bases, i.e., abasic sites. The damaging potential of IR is primarily related to the generation of electrons, which through their interaction with water produce free radicals. In their turn, free radicals attack DNA, proteins and lipids. Damage is induced also through direct deposition of energy. These types of IR interactions with biological materials are collectively called 'targeted effects', since they refer only to the irradiated cells. Earlier and sometimes 'anecdotal' findings were pointing to the possibility of IR actions unrelated to the irradiated cells or area, i.e., a type of systemic response with unknown mechanistic basis. Over the last years, significant experimental evidence has accumulated, showing a variety of radiation effects for 'out-of-field' areas (non-targeted effects-NTE). The NTE involve the release of chemical and biological mediators from the 'in-field' area and thus the communication of the radiation insult via the so called 'danger' signals. The NTE can be separated in two major groups: bystander and distant (systemic). In this review, we have collected a detailed list of proteins implicated in either bystander or systemic effects, including the clinically relevant abscopal phenomenon, using improved text-mining and bioinformatics tools from the literature. We have identified which of these genes belong to the DNA damage response and repair pathway (DDR/R) and made protein-protein interaction (PPi) networks. Our analysis supports that the apoptosis, TLR-like and NOD-like receptor signaling pathways are the main pathways participating in NTE. Based on this analysis, we formulate a biophysical hypothesis for the regulation of NTE, based on DNA damage and apoptosis gradients between the irradiation point and various distances corresponding to bystander (5mm) or distant effects (5cm). Last but not least, in order to provide a more realistic support for our model, we calculate the expected DSB and non-DSB clusters along the central axis of a representative 200.6MeV pencil beam calculated using Monte Carlo DNA damage simulation software (MCDS) based on the actual beam energy-to-depth curves used in therapy. PMID- 26873649 TI - Diffuse calcinosis cutis in systemic lupus erythematosus: an exceptional complication. PMID- 26873648 TI - Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity. AB - CCL25-mediated activation of CCR9 is critical for mucosal lymphocyte recruitment to the intestine. In immune-mediated liver injury complicating inflammatory bowel disease, intrahepatic activation of this pathway allows mucosal lymphocytes to be recruited to the liver, driving hepatobiliary destruction in primary sclerosing cholangitis (PSC). However, in mice and healthy humans CCL25 expression is restricted to the small bowel, whereas few data exist on activation of this pathway in the inflamed colon despite the vast majority of PSC patients having ulcerative colitis. Herein, we show that colonic CCL25 expression is not only upregulated in patients with active colitis, but strongly correlates with endoscopic Mayo score and mucosal TNFalpha expression. Moreover, approximately 90% (CD4(+)) and 30% (CD8(+)) of tissue-infiltrating T-cells in colitis were identified as CCR9(+) effector lymphocytes, compared to <10% of T-cells being CCR9(+) in normal colon. Sorted CCR9(+) lymphocytes also demonstrated enhanced cellular adhesion to stimulated hepatic sinusoidal endothelium compared with their CCR9(-) counterparts when under flow. Collectively, these results suggest that CCR9/CCL25 interactions are not only involved in colitis pathogenesis but also correlate with colonic inflammatory burden; further supporting the existence of overlapping mucosal lymphocyte recruitment pathways between the inflamed colon and liver. PMID- 26873650 TI - Biologic therapies in patients with neuropsychiatric systemic lupus erythematosus. PMID- 26873652 TI - Mirtazapine, in orodispersible form, for patients with preoperative psychological distress: A pilot study. AB - BACKGROUND: Perioperative psychological distress is associated with preoperative anxiety, depression, and postoperative pain. Mirtazapine is effective as an antidepressant, anxiolytic agent, and sleep enhancer. Moreover, mirtazapine can be made as orodispersible tablets with a fast onset for patients in nil per os status. This study is to determine whether mirtazapine can help psychologically distressed patients reduce perioperative anxiety, depression, and postoperative pain. MATERIALS AND METHODS: Patients with preoperative psychological distress, undergoing major abdominal surgery, were inquired and assigned to two groups according to their own choice. In the treatment group, patients could choose to take orodispersible mirtazapine 30 mg at each night from Preoperative Day 0 to Postoperative Day 3. There was no other intervention in the nontreatment group. Hospital Anxiety and Depression Scale (HADS), Athens Insomnia Scale (AIS), and pain scores were accessed on the day before operation (Day 0), and on the 1(st) day (Day 2) and 3(rd) day (Day 4) after operation. We compared the HADS, AIS, and pain scores, and morphine consumptions between the two groups on a daily basis. Marginal regression models were fitted to our correlated longitudinal data alone with the generalized estimating equations method to estimate the population average effects of time-varying mirtazapine usage on the mean values of HADS, AIS, and pain scores, and daily morphine consumptions. RESULTS: From September 2007 to December 2008, 86 patients agreed to be enrolled and 79 of them completed the study. Propensity scores and multivariate analysis showed that mirtazapine reduced HADS scores of patients in 2 days. Trial results indicated that mirtazapine lowered the AIS day index and tended to decrease night index as well. Mirtazapine may reduce patients' morphine consumption, but this effect was not statistically significant (p = 0.2). CONCLUSION: Mirtazapine helps reduce anxiety, depression, and insomnia scores for patients with perioperative psychological distress. PMID- 26873651 TI - Predicting decline of kidney function in lupus nephritis using urine biomarkers. AB - OBJECTIVE: To evaluate candidate biomarkers to predict future renal function decline (RFD) in children and adults with lupus nephritis (LN). METHODS: At the time of enrollment into prospective observational LN cohort studies liver-type fatty acid binding protein (LFABP), albumin, monocyte chemoattractant protein-1 (MCP-1), uromodulin, transferrin, and hepcidin were measured in urine samples of two cohorts of patients with LN, one followed at a pediatric (cohort-1; n = 28) and one at an adult institution (cohort-2; n = 69). The primary outcome was RFD, defined in cohort-1 as a decrease in estimated glomerular filtration rate (eGFR) of >=20% and in cohort-2 as a sustained increase of >=25% in serum creatinine concentration (SCr), both from baseline. RESULTS: All patients (n = 97) had normal eGFR or SCr at the time of urine collection at baseline. RFD occurred in 29% (8/28) of patients in cohort-1 during a mean follow-up of 6.1 months, and in 30% (21/69) of those in cohort-2 during a mean follow-up of 60 months. Individually, in cohort-1, levels of MCP-1, transferrin, LFABP, and albumin were higher in the RFD group than those who maintained renal function, with statistical significance for LFABP and albumin. In cohort-2 the RFD group also had higher levels of urine MCP-1 and albumin than others. The combination of LFABP, MCP-1, albumin, and transferrin had good predictive accuracy for RFD in both cohorts (area under the ROC curve = 0.77-0.82). CONCLUSION: The combinatorial urine biomarker LFABP, MCP-1, albumin, and transferrin shows promise as a predictor of renal functional decline in LN, and warrants further investigation. PMID- 26873654 TI - Reply. PMID- 26873653 TI - Reactive Oxygen Species Imaging in a Mouse Model of Inflammatory Bowel Disease. AB - PURPOSE: Reactive oxygen species (ROS) are important contributors to inflammatory bowel disease (IBD); however, there are insufficient tools for their in vivo evaluation. PROCEDURES: To determine if a chemiluminescent ROS reporter, coelenterazine, would be a useful tool for the detection of immune cell activation, the macrophage cell line (RAW 264.7) was treated with phorbol myristate acetate (PMA). Additionally, coelenterazine was used to monitor the changes in ROS production over time in a mouse model of IBD. RESULTS: In vitro, coelenterazine enabled the dynamic monitoring of the RAW 264.7 cell oxidative burst. In vivo, there were early, preclinical, changes in the localization and magnitude of coelenterazine chemiluminescent foci. CONCLUSIONS: Coelenterazine offers a high-throughput method for assessing immune cell activation in culture and provides a means for the in vivo detection and localization of ROS during IBD disease progression. PMID- 26873655 TI - Elevated Blood Pressure with Reduced Left Ventricular and Aortic Dimensions in Adolescents Born Extremely Preterm. AB - OBJECTIVE: To evaluate the long-term cardiovascular effects of extremely preterm birth in a cohort of adolescents followed prospectively, who were largely free from intrauterine growth restriction. STUDY DESIGN: Central blood pressures, aortic and cardiac dimensions, left ventricle (LV) function, pulse wave velocity, augmentation index, and microvascular reactive hyperemia were measured in 18-year old subjects born extremely preterm at <28 weeks' gestation (n = 109) and term born controls (n = 81). RESULTS: Compared with controls, preterm adolescents had higher systolic (124 +/- 13 vs 118 +/- 10 mm Hg, P = .002) and diastolic (72 +/- 8 vs 67 +/- 7 mm Hg, P < .001) blood pressures, but lower ascending aortic z scores (0.13 +/- 0.89 vs 0.42 +/- 0.78, P = .02), LV diastolic (48.5 +/- 4 vs 50.3 +/- 4.5 mm, P = .007) and systolic (30.2 +/- 3.5 vs 31.9 +/- 4.0 mm, P = .003) diameters, and a reduced LV mass (130 +/- 34 vs 145 +/- 41 g, P = .01) and mass index (75 +/- 14 vs 81 +/- 16 g/m(2), P = .02). However, LV relative wall thickness, LV function, pulse wave velocity, augmentation index, and microvascular reactive hyperemia were similar. Within the ex-preterm group, there were no significant relationships between birthweight z-scores and any cardiovascular measures, once the latter were adjusted for current body size. CONCLUSIONS: Extremely preterm birth had relatively minor cardiovascular effects in late-adolescence, with increased blood pressures, decreased LV, and aortic size, but preserved LV function, macrovascular properties, and microvascular function. In utero growth was not independently related to cardiovascular function within the ex-preterm cohort. PMID- 26873657 TI - Development and Psychometric Testing of a Scale for Evaluating Self-Management Needs of Knee Osteoarthritis (SMNKOA) in Taiwan. AB - Self-management of osteoarthritis (OA) of the knee is important for treating this chronic disease. This study developed and psychometrically tested a new instrument for measuring adult patients' self-management needs of knee osteoarthritis (SMNKOA). The theoretical framework of self-care guided the development of the 35-item SMNKOA scale. Participants ( N = 372) were purposively sampled from orthopedic clinics at medical centers in Taiwan. The content validity index was 0.83. Principal components analysis identified a three-factor solution, accounting for 53.19% of the variance. The divergent validity was 0.67; convergent validity was -0.51. Cronbach's alpha was .95, Pearson's correlation coefficient was .88, and the intraclass correlation coefficient was .95. The scale's reliability and validity supports the SMNKOA, as a tool to measure self-management needs of adults with knee OA. Nurses and other health care providers can use this instrument to evaluate knee OA patients and identify strategies for improving health-related outcomes and patient education. PMID- 26873658 TI - A Pilot Randomized Controlled Trial Using Prophylactic Dressings to Minimize Sacral Pressure Injuries in High-Risk Hospitalized Patients. AB - This pilot randomized controlled trial examined the effect of prophylactic dressings to minimize sacral pressure injuries (PIs) in high-risk hospitalized patients and assessed feasibility criteria to inform a larger study. Eighty patients were recruited at admission points (the emergency department and surgical care unit) or directly from participating wards in the general medical surgical setting following the assessment of high risk of sacral PI. Participants were randomized into either the routine care or routine care and silicone foam border dressing group. Outcome assessment comprised digital photographs of each participant's sacrum every 72 hr for evaluation by a blind-to-intervention assessor. Sixty-seven participants had at least one sacral photograph taken and assessed by a blind-to-intervention assessor. Three participants were assessed as having a Stage I PI. Although the use of photography was effective, feasibility criteria identified challenges related to bias, blinding, weight assessment, preparation of nursing staff, and sample size estimation. PMID- 26873656 TI - Increases in Sex Hormones during Anti-Tumor Necrosis Factor alpha Therapy in Adolescents with Crohn's Disease. AB - OBJECTIVE: To evaluate children with Crohn's disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-tumor necrosis factor alpha (TNF-alpha) therapy. STUDY DESIGN: An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-alpha therapy and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2-5) with Crohn's disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation, and dual-energy x-ray absorptiometry whole-body fat mass Z scores over the study interval. RESULTS: Sex hormone Z scores increased significantly during the 10-week induction interval: testosterone Z scores in male patients increased from a median of -0.36 to 0.40 (P < .05) and estradiol Z scores in females increased from -0.35 to -0.02 (P < .01). In mixed model regression, the pediatric Crohn's disease activity index score, cytokine levels, and measures of inflammation were significantly and negatively associated with sex hormone Z scores and with luteinizing hormone and follicle-stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with body mass index or fat mass Z-scores. CONCLUSIONS: Crohn's disease is associated with delayed maturation, and initiation of anti-TNF-alpha therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in association with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation. PMID- 26873659 TI - Effect of curing light emission spectrum on the nanohardness and elastic modulus of two bulk-fill resin composites. AB - OBJECTIVE: To determine the nanohardness and elastic moduli of two bulk-fill resin based composites (RBCs) at increasing depths from the surface and increasing distances laterally from the center after light curing. METHODS: Two bulk-fill dental RBCs: Tetric EvoCeram Bulk Fill (TECBF) and Filtek Bulk Fill Flowable (FBFF) were light cured in a metal mold with a 6mm diameter and a 10mm long semi-circular notch. The RBCs were photo-polymerized for 10s using a light emitting diode (LED) Bluephase Style curing light, with the original light probe that lacked the homogenizer. This light has two blue light and one violet light LED emitters. By changing the probe orientation over the mold, the light output from only two LEDs reached the RBC. Measurements were made using: (i) the light from one violet and one blue LED, and (ii) the light from the two blue LEDs. Five specimens of each RBC were made using each LED orientation (total 20 specimens). Specimens were then stored in the dark at 37 degrees C for 24h. Fifty indents were made using an Agilent G200 nanoindentor down to 4mm from the surface and 2.5mm right and left of the centerline. The results were analyzed (alpha=0.05) using multiple paired-sample t-tests, ANOVA, Bonferroni post-hoc tests, and Pearson correlations. RESULTS: The elastic modulus and nanohardness varied according to the depth and the distance from the centerline. For TECBF, no significant difference was found between the spatial variations in the elastic modulus or hardness values when violet-blue or blue-blue LEDs were used. For FBFF, the elastic modulus and nanohardness on the side exposed to the violet emitter were significantly less than the side exposed to the blue emitter. A strong correlation between nanohardness and elastic modulus was found in all groups (r(2)=0.9512-0.9712). SIGNIFICANCE: Resin polymerization was not uniform throughout the RBC. The nanohardness and elastic modulus across two RBC materials were found to decline differently according to the orientation of the violet and blue light LED emitters within the curing light. PMID- 26873660 TI - Clinical trials: Randomization, completeness of data and restoration longevity. PMID- 26873661 TI - The recent progress in proteochemometric modelling: focusing on target descriptors, cross-term descriptors and application scope. AB - As an extension of the conventional quantitative structure activity relationship models, proteochemometric (PCM) modelling is a computational method that can predict the bioactivity relations between multiple ligands and multiple targets. Traditional PCM modelling includes three essential elements: descriptors (including target descriptors, ligand descriptors and cross-term descriptors), bioactivity data and appropriate learning functions that link the descriptors to the bioactivity data. Since its appearance, PCM modelling has developed rapidly over the past decade by taking advantage of the progress of different descriptors and machine learning techniques, along with the increasing amounts of available bioactivity data. Specifically, the new emerging target descriptors and cross term descriptors not only significantly increased the performance of PCM modelling but also expanded its application scope from traditional protein-ligand interaction to more abundant interactions, including protein-peptide, protein-DNA and even protein-protein interactions. In this review, target descriptors and cross-term descriptors, as well as the corresponding application scope, are intensively summarized. Additionally, we look forward to seeing PCM modelling extend into new application scopes, such as Target-Catalyst-Ligand systems, with the further development of descriptors, machine learning techniques and increasing amounts of available bioactivity data. PMID- 26873662 TI - Association between position of the fixed ulnar head and carpal translocation after the Sauve-Kapandji procedure in patients with rheumatoid arthritis. AB - OBJECTIVE: The Sauve-Kapandji procedure is a common surgical procedure for rheumatoid wrist, which involves fixing dissected ulnar head to the distal radius in order to provide "bony support" to the carpus. The purpose of this study was to investigate whether the position of the fixed ulnar head was associated with postsurgical carpus translocation. METHODS: We retrospectively reviewed radiographs of 40 patients who underwent the Sauve-Kapandji procedure and were subsequently followed up for over two years. The association between the fixed ulnar head position and postsurgical carpus translocation was statistically analysed with a confidence interval of 95% (p < 0.05). RESULTS: Multiple regression analysis suggested that the radial inclination of the fixed ulnar head, the absence of increases in ulnar variance, and wide "bony support" were significantly associated with less postsurgical carpal translocation. CONCLUSION: Our study indicated that good concordance between the "bony support" and the carpus might be important in reducing postsurgical carpus translocation. PMID- 26873663 TI - On central nervous system involvement in variants of Guillain-Barre syndrome and Miller Fisher overlap. PMID- 26873664 TI - The power of historical data for assessment of childhood vaccine benefits. PMID- 26873665 TI - Effect of vaccination programmes on mortality burden among children and young adults in the Netherlands during the 20th century: a historical analysis. AB - BACKGROUND: In the 20th century, childhood mortality decreased rapidly, and vaccination programmes are frequently suggested as a contributing factor. However, quantification of this contribution is subject to debate or absent. We present historical data from the Netherlands that allow us to quantify the reduction in childhood mortality burden for vaccine-preventable diseases in this period as a function of vaccination coverage. METHODS: We retrieved cause specific and age-specific historical mortality data from Statistics Netherlands from 1903 to 2012 (for Dutch birth cohorts born from 1903 to 1992), and data for vaccination coverage since the start of vaccination programmes from the Dutch Health Care Inspectorate and the Dutch National Institute for Public Health and the Environment. We also obtained birth and migration data from Statistics Netherlands. We used a restricted mean life-time method to estimate cause specific mortality burden among children and young adults for each birth cohort as the years of life lost up to age 20 years, excluding migration as a variable because this did not affect the results. To correct for long-term trends, we calculated the cause-specific contribution to the total childhood mortality burden. FINDINGS: In the prevaccination era, the contribution to mortality burden was fairly constant for diphtheria (1.4%), pertussis (3.8%), and tetanus (0.1%). Around the start of mass vaccinations, these contributions to the mortality burden decreased rapidly to near zero. We noted similar patterns for poliomyelitis, mumps, and rubella. The number of deaths due to measles around the start of vaccination in the Netherlands were too few to detect an accelerated rate of decrease after mass vaccinations were started. We estimate that mass vaccination programmes averted 148 000 years of life lost up to age 20 years (95% prediction interval 110 000-201 000) among children born before 1992. This corresponds to about 9000 deaths averted (6000-12 000). INTERPRETATION: Our historical time series analysis of mortality and vaccination coverage shows a strong association between increasing vaccination coverage and diminishing contribution of vaccine-preventable diseases to overall mortality. This analysis provides further evidence that mass vaccination programmes contributed to lowering childhood mortality burden. FUNDING: Dutch Ministry of Health, Welfare and Sport. PMID- 26873666 TI - The Ills of Marginality: New Perspectives on Health in South Asia. AB - Social marginality and ill health can form an unholy dyad: firstly, groups who suffer from chronic or infectious diseases often find themselves pushed to the margins. Secondly, people who are already on the edge of society tend to suffer more from illness than those at the centre. In development discourse, marginal people are defined as those who are 'not yet' on the same level as the developed mainstream and are in urgent need of aid from the centre. The papers in this special issue take a different approach by insisting that marginality is a radically relational concept: the centre and its margins constitute each other, and the boundaries between them are constantly shifting. The papers show that there are many types of marginality (based on geography, class, caste, sex/gender, ethnicity, etc.), and that each of them has different effects on the health of a particular group. Yet instead of speaking of a plurality of unrelated 'group identities', marginality preserves a sharp sense of unequal power relations between groups. The specific ethnographic contribution to the study of marginality comes from its attention to the point of view of marginal people. This is of critical importance since marginality puts health most under stress when it is clearly and steadily perceived in everyday life. This, in turn, makes it possible to show that living on the margins is not always and everywhere bad for health. While all of the papers present South Asian case studies, the insights and questions are relevant for the study of the ills of marginality in a global perspective. PMID- 26873667 TI - 'Do not resist, show me your body!': Encounters Between the Jarwas of the Andamans and Medicine (1858-2004). AB - Based on fieldwork and archival studies carried out since 1995, this paper is an analysis of the dialogue between the Jarwas and the outside world. The Jarwa tribal community on the Andaman Islands has a long history of voluntary isolation and pronounced hostility towards outsiders. This situation only started to change in the mid-1990s, when a young Jarwa was successfully treated at a local hospital. The Jarwas' sudden fascination with modern medicine was less to do with its therapeutic powers than the fact that, on each visit, hospital staff gave them food, clothes, and various consumer items. This paper describes events in the Jarwas' 'junket to modernity'. Before discussing recent events, the paper first retraces the history of relations between the Jarwas and the outside world during the second half of the 19th century, when life on the Andaman Islands was dominated by a British Penal Settlement. In the face of epidemic outbreaks of pneumonia, malaria, and measles, tribal health has become a major concern for the Indian authorities. The paper discusses continuities and discontinuities in medical concerns with the tribal body, and argues that 'marginalization' must be understood as a practice of mutual constitution. PMID- 26873668 TI - The Effects of Inequality and Relative Marginality on the Well-being of Low Caste People in Central Uttaranchal. AB - Perceived marginality can have a great impact on people's well-being. Using ethnographic material from three different low-caste villages in the Central Himalayas of North India, and based on a survey of Garhwali women conducted in 2002-03, this paper illustrates that marginality and well-being are never absolute but always relative. Discussing anthropological aspects of the bodily experience of oppression, and Public Health studies of the effects of social inequalities on health, it will be argued that the relative marginality of low caste people within their villages affects their well-being much more than the absolute caste status on the district or state level. PMID- 26873669 TI - Pharmaceutical Citizenship: Antidepressant Marketing and the Promise of Demarginalization in India. AB - Among practitioners of biomedicine, to speak of people as 'marginalized' often amounts to saying that they do not have access to medical substances. Thus conceived, the best way to remove marginality seems to be to give medicines to those deprived of them. The peculiar relationship between marginality and pharmaceuticals is especially poignant in the case of antidepressant drugs, as these drugs appear to bring the patient 'back into society', but not any society, but middle-class consumer society. What is now special about antidepressants is that there is nothing special about them: antidepressants are like consumer items among thousands of other consumer items. This paper explores the relations between medicines and marginality with reference to the marketing of antidepressant drugs in Kolkata (Calcutta), India. Drawing on ethnographic fieldwork in the Kolkata metropolitan area from July 1999 to December 2000 and in August/September 2003, this paper examines how people with depression are constituted as 'marginal' in the sense of 'being deprived of medication', and how the biomedical promise of an effective pharmacological treatment becomes a promise of 'pharmaceutical citizenship'. In view of Bengali notions of mental health as a state of detachment, the paper asks if pharmacological demarginalization holds the same promise in the Indian context that it holds in the West. PMID- 26873670 TI - Geographies of contagion: Hijras, Kothis, and the politics of sexual marginality in Hyderabad. AB - Following the recognition that 'culture matters' in designing effective public health programs, this paper focuses on one refraction of culture within the so called 'homosexual' community in India, to highlight how attention to local knowledge and its socio-economic underpinnings can impact the politics of health care. Drawing primarily on ethnographic fieldwork conducted from 1995-1997 and 2003 in the South Indian city of Hyderabad among hijras (the so-called third sex of India) as well as the wider community of MSM or 'men who have sex with men', the paper argues that public health framings of homosexuality often fail to pay attention to differential understandings of stigma and their socio-economic underpinnings, a failure that accounts in some measure for the ineffectiveness of prevention programs targeted at 'high risk' communities such as hijras and MSM. Focusing on the local moral economy of respect and shame as one pathway of stigma and contagion, and in particular on the differences in constructions of respect and shame between hijras and the wider community of MSM, this paper points at one small way in which understanding how culture matters can ultimately address the ineffectiveness of prevention programs and redress the inequalities in health outcomes between the various margins and centers of power. PMID- 26873671 TI - Deportability, Medicine, and the Law. AB - This paper explores the institutional and everyday conditions that define 'deportability' as a lived experience at the social margin. Focusing on Germany as a paradigmatic case for the new immigration and deportation policies of the new Europe, it investigates state rationales through which certain bodies are produced as 'deportable' and takes a specific look at the role of medicine in this matter. The first part of the text traces a genealogy of various forms of medical intervention. Based on ethnographic fieldwork carried out from September 2003 to April 2005 in an institutional setting in Frankfurt/Main, the main focus of the discussion is the situation of traumatized refugees and asylum seekers, for whom German asylum and immigration law reserves special conditions. The second part investigates how the issue of deportability is negotiated by Punjabis in Germany's Rhein-Main area. It can be discerned from both perspectives-state centred as well as community-centred-that the body of the migrant has become a locus of otherness and bearer of debts in relation to the state. And yet the margin acquires significantly different meanings when approached through an ethnography of migrant communities and localities, for it is here that, as a social context and particular form, the margin is both a lived reality and site of intervention. PMID- 26873672 TI - Reviews. PMID- 26873673 TI - (1R,2S,6R)-Papayanal: a new male-specific volatile compound released by the guava weevil Conotrachelus psidii (Coleoptera: Curculionidae). AB - The guava weevil, Conotrachelus psidii is an aggressive pest of guava (Psidium guajava L.) that causes irreparable damages inside the fruit. The volatile compounds of male and female insects were separately collected by headspace solid phase microextraction or with dynamic headspace collection on a polymer sorbent, and comparatively analyzed by GC-MS. (1R,2S,6R)-2-Hydroxymethyl-2,6-dimethyl-3 oxabicyclo[4.2.0]octane (papayanol), and (1R,2S,6R)-2,6-dimethyl-3 oxabicyclo[4.2.0]octane-2-carbaldehyde (papayanal) were identified (ratio of 9:1, respectively) as male-specific guava weevil volatiles. Papayanal structure was confirmed by comparison of spectroscopic (EIMS) and chromatographic (retention time) data with those of the synthetic pure compound. The behavioral response of the above-mentioned compounds was studied in a Y-tube olfactometer bioassay, and their role as aggregation pheromone candidate components was suggested in this species. PMID- 26873675 TI - Challenging the cervix: strategies to overcome the anatomic impediments to hysteroscopy: analysis of 31,052 office hysteroscopies. AB - OBJECTIVE: To report our experience on 10,156 cases of cervical stenosis (CS) diagnosed at office hysteroscopy. DESIGN: Retrospective study. SETTING: Ambulatory clinics of diagnostic and operative hysteroscopy of two university teaching hospitals (Naples and Bari). PATIENT(S): A total of 31,052 patients undergoing office hysteroscopy. INTERVENTION(S): All of the paper and electronic reports of the office hysteroscopies performed from January 1996 to September 2014 were reviewed. Hysteroscopies were classified as successful (i.e., when access to and visualization of the entire uterine cavity was possible during the same procedure), incomplete (i.e., when access to uterine cavity was possible, but the entire uterine cavity could not be examined), or failed (i.e., when access to uterine cavity was not possible). CS was classified on the basis of localization: stenosis of external cervical ostium (ECO; type I); stenosis of distal third of cervical channel and the internal cervical ostium (ICO; type II); stenosis of the ICO (type III), and combined stenosis of ECO and ICO (type IV). MAIN OUTCOME MEASURE(S): The success rate at overpassing CS (including both successful and incomplete hysteroscopies) was the primary outcome measure. Secondary outcome measures were frequency and localization of CS in fertile and postmenopausal women and the frequency of use of technical maneuvers and/or miniaturized mechanical or bipolar instruments to overcome them. RESULT(S): All hysteroscopies were performed with the use of a 5- or 4-mm rigid continuous-flow office operative hysteroscope by operators with different levels of expertise. The hysteroscopy technique used was standardized between the two centers and among all of the surgeons throughout the years. An access to the uterine cavity with a complete evaluation of the whole endometrial surface was possible in 93.9% of cases (29,152 patients). The main reasons of the 1,320 (4.3%) incomplete and 580 (1.9%) failed hysteroscopies were pain and CS, respectively. CS was identified in 10,156 women (32.7% of all procedures) and was significantly more frequent in postmenopausal than in fertile women (70.1% vs. 29.9%), except for type I stenosis, which was more frequent in fertile than in postmenopausal women. Type IV CS (44.3%) was the most commonly detected. Overall, CS was managed successfully with minimal discomfort in 98.5% of cases with technical maneuvers and miniaturized mechanical and/or bipolar instruments. Adhesiolysis with the distal tip of the hysteroscope by rotating the scope on the endocamera was the significantly more used strategy to overpass all types of CS (39.8% of cases), generally used in combination with miniaturized operative instruments (79.2%). Bipolar electrodes were more used in cases of type I and type IV stenosis (39.7%) compared with the other types of CS. CONCLUSION(S): CS and pain represent the main reasons for failed hysteroscopy. Recent technical and technologic innovations, together with increased operator experience and optimal pain management, have made it possible to overcome even severe CS with the use of office hysterosocpy, thus significantly reducing the rate of failed procedures and the need for operating room and general anesthesia. PMID- 26873674 TI - Lenalidomide treatment of cutaneous lupus erythematosus: the Mayo Clinic experience. AB - BACKGROUND: Published case series describe lenalidomide as an effective treatment of refractory cutaneous lupus erythematosus (CLE). OBJECTIVES: The present study aimed to further characterize lenalidomide use in the treatment of CLE. METHODS: A retrospective review of patients treated with lenalidomide for CLE from January 1, 2000, to December 17, 2014, was conducted. RESULTS: Eight of the nine patients (89%) were women. Their median age at initiation of lenalidomide was 62 years (range: 41-86 years). Subtypes of CLE included discoid lupus erythematosus (DLE) (n = 6), lupus panniculitis (n = 2), and subacute CLE (n = 1). Before the initiation of lenalidomide, all patients had been previously treated unsuccessfully or were intolerant to at least one antimalarial and one immunosuppressive agent. With lenalidomide, five patients achieved a complete response (CR), two a partial response, and two had no response (lupus panniculitis). Time to initial response (dose range: 2.5-10.0 mg/d) varied from 2 weeks to 3 months; the median time to CR in five patients was 3 months (range: 3 6 months). The median duration of lenalidomide therapy was 12 months (range: 2-67 months). The median duration of follow-up was 48 months (range: 20-103 months). Adverse effects included mild leukopenia; one patient had deep vein thrombosis of unclear etiology during a hospitalization. No patients developed or showed progression of systemic LE while receiving lenalidomide. CONCLUSIONS: Lenalidomide was effective for the treatment of CLE (particularly DLE) but not for the treatment of lupus panniculitis in this series. PMID- 26873676 TI - Single-molecule mass spectrometry. AB - In single-molecule mass spectrometry, the mass of each ion is measured individually; making it suitable for the analysis of very large, heterogeneous objects that cannot be analyzed by conventional means. A range of single-molecule mass spectrometry techniques has been developed, including time-of-flight with cryogenic detectors, a quadrupole ion trap with optical detection, single molecule Fourier transform ion cyclotron resonance, charge detection mass spectrometry, quadrupole ion traps coupled to charge detector plates, and nanomechanical oscillators. In addition to providing information on mass and heterogeneity, these techniques have been used to study impact craters from cosmic dust, monitor the assembly of viruses, elucidate the fluorescence dynamics of quantum dots, and much more. This review focuses on the merits of each of these technologies, their limitations, and their applications. (c) 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:715-733, 2017. PMID- 26873677 TI - Prophylactic neck dissection for low-risk differentiated thyroid cancers: Risk benefit analysis. AB - BACKGROUND: The benefit of neck dissection is the subject of debate in differentiated thyroid cancer (DTC). We analyze the risk-benefit of neck dissection for low-risk DTC without detectable lymph nodes. METHODS: We conducted a retrospective study from 1983 to 2003; which included 295 patients without detectable lymph nodes who were treated by thyroidectomy with (C+) or without (C ) neck dissection. All patients had iodine131 therapy. We compared the frequency of remission, disease progression, and permanent complications between groups. RESULTS: Two hundred twelve patients comprised the C+ group, and 83 patients the C- group. Respectively for C+ versus C-, remission rates were 92% versus 89.2% (p = .40), and progressive disease observed was 3.3% versus 7.2% (p = .10). Permanent hypoparathyroidism occurred in 15.1% in C+ versus 3.6% in C- (p = .006). CONCLUSION: The risk-benefit analysis of neck dissection in patients with low-risk DTC shows no benefit in terms of complete remission or occurrence of progression. However, risk of complications seems to be higher in patients with neck dissection. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1091-1096, 2016. PMID- 26873678 TI - Women's fertility desires and contraceptive behavior in three peri-urban communities in sub Saharan Africa. AB - BACKGROUND: Fertility desires and contraceptive behavior often change over time. This study examined the influence of change in fertility desires on change in modern contraceptive use over time in three peri-urban communities in sub-Saharan Africa. METHODS: This multi-site study includes baseline and follow up data from 3 sites in the Family Health and Wealth Study. Following a census in each site, a probability sample of at least 500 households was obtained. Generalized linear models were employed. RESULTS: Modern contraceptive use increased in Ipetumodu, Nigeria (29.4% to 36.7%), but declined slightly in Sebeta, Ethiopia (66.9% to 61.3%) and Asawase, Ghana (12.6% to 10.8%). Across sites, at baseline and follow up, women who wanted no more children reported more contraceptive use, compared with those who wanted more children, and were more likely to shift to being contraceptive users in Ipetumodu [aOR(95% CI):1.55 (1.07,2.26)]. CONCLUSIONS: Women's fertility desires influenced their contraceptive behavior, although there were cross-site differences. Changing contraceptive demand and program factors will be important to enable peri-urban women to frame and act on their fertility desires. PMID- 26873679 TI - Impact of Environmental Enrichment Devices on NTP In Vivo Studies. AB - The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13 week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices. PMID- 26873680 TI - Metabolic Syndrome in Adults With Congenital Heart Disease. AB - BACKGROUND: Metabolic syndrome increases risk for atherosclerotic coronary artery disease, and its prevalence increases with increasing age and body mass index. Adults with congenital heart disease (ACHD) are now living longer and accruing coronary artery disease risk factors. However, the prevalence of metabolic syndrome in ACHD patients is unknown. METHODS AND RESULTS: We conducted a retrospective cohort study of ACHD patients at our center to quantify the prevalence of metabolic syndrome in an ACHD population. Using case-control matching, we constructed a comparable control group from a population-based sample of 150 104 adults. International Diabetes Federation criteria were used to define metabolic syndrome. We used logistic regression to compare the risk of metabolic syndrome across the resulting cohorts, which were composed of 448 ACHD patients and 448 controls matched by age and sex. Mean age of both groups was 32.4+/-11.3 years, and 51.3% were female. Obesity was present in 16.1% of the ACHD patients and 16.7% of the controls. Metabolic syndrome was more common in ACHD patients than in controls (15.0% versus 7.4%; odds ratio 1.82, 95% CI 1.25 2.65). CONCLUSIONS: Our data suggest that metabolic syndrome is more common among adults with congenital heart disease than in the general population. Thus, patients with congenital heart disease should be screened for metabolic syndrome and risk factors mitigated where possible to prevent atherosclerotic coronary artery disease. Preventive cardiology should be included during routine ACHD care. PMID- 26873681 TI - Effect of Visit-to-Visit Variation of Heart Rate and Systolic Blood Pressure on Outcomes in Chronic Systolic Heart Failure: Results From the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT) Trial. AB - BACKGROUND: Elevated resting heart rate (HR) and low systolic blood pressure (SBP) are related to poor outcomes in heart failure (HF). The association between visit-to-visit variation in SBP and HR and risk in HF is unknown. METHODS AND RESULTS: In Systolic Heart Failure Treatment with the If inhibitor ivabradine Trial (SHIFT) patients, we evaluated relationships between mean HR, mean SBP, and visit-to-visit variations (coefficient of variation [CV]=SD/mean*100%) in SBP and HR (SBP-CV and HR-CV, respectively) and primary composite endpoint (cardiovascular mortality or HF hospitalization), its components, all-cause mortality, and all-cause hospitalization. High HR and low SBP were closely associated with risk for primary endpoint, all-cause mortality, and HF hospitalization. The highest number of primary endpoint events occurred in the highest HR tertile (38.8% vs 16.4% lowest tertile; P<0.001). For HR-CV, patients at highest risk were those in the lowest tertile. Patients in the lowest thirds of mean SBP and SBP-CV had the highest risk. The combination of high HR and low HR-CV had an additive deleterious effect on risk, as did that of low SBP and low SBP-CV. Ivabradine reduced mean HR and increased HR-CV, and increased SBP and SBP CV slightly. CONCLUSIONS: Beyond high HR and low SBP, low HR-CV and low SBP-CV are predictors of cardiovascular outcomes with additive effects on risk in HF, but with an unknown effect size. Beyond HR reduction, ivabradine increases HR-CV. Low visit-to-visit variation of HR and SBP might signal risk of cardiovascular outcomes in systolic HF. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/. Unique identifier: ISRCTN70429960. PMID- 26873682 TI - Are Changes in Heart Rate Variability in Middle-Aged and Older People Normative or Caused by Pathological Conditions? Findings From a Large Population-Based Longitudinal Cohort Study. AB - BACKGROUND: No study to date has investigated longitudinal trajectories of cardiac autonomic modulation changes with aging; therefore, we lack evidence showing whether these changes occur naturally or are secondary to disease or medication use. This study tested whether heart rate variability (HRV) trajectories from middle to older age are largely normative or caused by pathological changes with aging in a large prospective cohort. We further assessed whether HRV changes were modified by socioeconomic status, ethnicity, or habitual physical activity. METHODS AND RESULTS: This study involved 3176 men and 1238 women initially aged 44 to 69 years (1997-1999) from the UK Whitehall II population-based cohort. We evaluated time- and frequency-domain HRV measures of short-term recordings at 3 time points over a 10-year period. Random mixed models with time-varying covariates were applied. Cross-sectionally, HRV measures were lower for men than for women, for participants with cardiometabolic conditions, and for participants reporting use of medications other than beta blockers. Longitudinally, HRV measures decreased significantly with aging in both sexes, with faster decline in younger age groups. HRV trajectories were not explained by increased prevalence of cardiometabolic problems and/or medication use. In women, cardiometabolic problems were associated with faster decline in the standard deviation of all intervals between R waves with normal-to-normal conduction, in low-frequency HRV, and in low-frequency HRV in normalized units. Socioeconomic status, ethnicity, and habitual physical activity did not have significant effects on HRV trajectories. CONCLUSIONS: Our investigation showed a general pattern and timing of changes in indices of cardiac autonomic modulation from middle to older age. These changes seem likely to reflect the normal aging process rather than being secondary to cardiometabolic problems and medication use. PMID- 26873684 TI - Subcutaneous Implantable Cardioverter Defibrillator in Patients With Hypertrophic Cardiomyopathy: An Initial Experience. AB - BACKGROUND: The subcutaneous implantable cardioverter defibrillator (S-ICD) has been developed to avert risks associated with transvenous defibrillator leads. The technology is attractive for younger patients, such as those with hypertrophic cardiomyopathy (HCM). However, there are limited data on S-ICD use in HCM. METHODS AND RESULTS: HCM patients identified at risk for sudden death were considered for S-ICD implantation. Patients were screened for potential oversensing by surface electrocardiography (ECG). At implant, defibrillation threshold (DFT) testing was performed at 65, 50, and 35 joules (J). Twenty-seven patients were considered for S-ICD implantation, and after screening, 23 (85%) remained eligible. The presence of a bundle branch block was associated with screening failure, whereas elevated body mass index (BMI) showed a trend toward association. One patient passed screening at rest, but failed with an ECG obtained after exercise. At implant, the S-ICD terminated ventricular fibrillation (VF) with a 65J shock in all 15 implanted patients and a 50J shock was successful in 12 of 15. A 35J shock terminated VF in 10 of 12 patients. DFT failure at 50 J was associated with a higher BMI. There were no appropriate shocks after a median follow-up of 17.5 (3-35) months, and 1 patient received an inappropriate shock attributable to a temporary reduction in QRS amplitude while bending forward, resulting in oversensing, despite successful screening. CONCLUSIONS: In a high-risk HCM cohort without a pacing indication referred for consideration of an ICD, the majority were eligible for S-ICD. The S-ICD is effective at recognizing and terminating VF at implant with a wide safety margin. PMID- 26873683 TI - Midlife Cardiovascular Risk Factors and Late-Life Unrecognized and Recognized Myocardial Infarction Detect by Cardiac Magnetic Resonance: ICELAND-MI, the AGES Reykjavik Study. AB - BACKGROUND: Associations of atherosclerosis risk factors with unrecognized myocardial infarction (UMI) are unclear. We investigated associations of midlife risk factors with UMI and recognized MI (RMI) detected 31 years later by cardiac magnetic resonance. METHODS AND RESULTS: The Reykjavik Study (1967-1991) collected serial risk factors in subjects, mean (SD) age 48 (7) years. In ICELAND MI (2004-2007), 936 survivors (76 (5) years) were evaluated by cardiac magnetic resonance. Analysis included logistic regression and random effects modeling. Comparisons are relative to subjects without MI. At baseline midlife evaluation, a modified Framingham risk score was significantly higher in RMI and in UMI versus no MI (7.4 (6.3)%; 7.1 (6.2)% versus 5.4 (5.8)%, P<0.001). RMI and UMI were more frequent in men (65%, 64% versus 43%; P<0.0001). Baseline systolic and diastolic blood pressure were significantly higher in UMI (138 (17) mm Hg versus 133 (17) mm Hg; P<0.006; 87 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Diastolic BP was significantly higher in RMI (88 (10) mm Hg versus 84 (10) mm Hg; P<0.02). Cholesterol and triglycerides were significantly higher in RMI (6.7 (1.1) mmol/L versus 6.2 (1.1) mmol/L; P=0.0005; and 1.4 (0.7) mmol/L versus 1.1 (0.7) mmol/L; P<0.003). Cholesterol trended higher in UMI (P=0.08). Serial midlife systolic BP was significantly higher in UMI versus no MI (beta [SE] = 2.69 [1.28] mm Hg, P=0.04). Serial systolic and diastolic BP were significantly higher in RMI versus no MI (4.12 [1.60] mm Hg, P=0.01 and 2.05 [0.91] mm Hg, P=0.03) as were cholesterol (0.43 [0.11] mmol/L, P=0.0001) and triglycerides (0.3 [0.06] mmol/L, P<0.0001). CONCLUSIONS: Midlife vascular risk factors are associated with UMI and RMI detected by cardiac magnetic resonance 31 years later. Systolic blood pressure was the most significant modifiable risk factor associated with later UMI. PMID- 26873685 TI - Rates of Atrial Fibrillation in Black Versus White Patients With Pacemakers. AB - BACKGROUND: Black US residents experience higher rates of ischemic stroke than white residents but have lower rates of clinically apparent atrial fibrillation (AF), a strong risk factor for stroke. It is unclear whether black persons truly have less AF or simply more undiagnosed AF. METHODS AND RESULTS: We obtained administrative claims data from state health agencies regarding all emergency department visits and hospitalizations in California, Florida, and New York. We identified a cohort of patients with pacemakers, the regular interrogation of which reduces the likelihood of undiagnosed AF. We compared rates of documented AF or atrial flutter at follow-up visits using Kaplan-Meier survival statistics and Cox proportional hazards models adjusted for demographic characteristics and vascular risk factors. We identified 10 393 black and 91 380 white patients without documented AF or atrial flutter before or at the index visit for pacemaker implantation. During 3.7 (+/-1.8) years of follow-up, black patients had a significantly lower rate of AF (21.4%; 95% CI 19.8-23.2) than white patients (25.5%; 95% CI 24.9-26.0). After adjustment for demographic characteristics and comorbidities, black patients had a lower hazard of AF (hazard ratio 0.91; 95% CI 0.86-0.96), a higher hazard of atrial flutter (hazard ratio 1.29; 95% CI 1.11-1.49), and a lower hazard of the composite of AF or atrial flutter (hazard ratio 0.94; 95% CI 0.88-99). CONCLUSIONS: In a population based sample of patients with pacemakers, black patients had a lower rate of AF compared with white patients. These findings indicate that the persistent racial disparities in rates of ischemic stroke are likely to be related to factors other than undiagnosed AF. PMID- 26873686 TI - Impact of Nitrate Use on Survival in Acute Heart Failure: A Propensity-Matched Analysis. AB - BACKGROUND: There is limited evidence that the use of nitrates in acute decompensated heart failure early after presentation to a hospital can improve clinical outcomes. We aimed to determine whether early nitrate exposure is associated with improved survival in a large retrospective cohort study. METHODS AND RESULTS: We examined 11 078 acute decompensated heart failure patients who presented to emergency departments in Ontario, Canada, between 2004 and 2007, in the Enhanced Feedback For Effective Cardiac Treatment and the Emergency Heart failure Mortality Risk Grade studies. In propensity-matched analyses, we examined the effect of nitrate administration in the acute emergency department setting for its impact on death at 7, 30, and 365 days. In propensity-matched analyses, we found no difference in survival between those who received nitrates in the emergency department and the non-nitrate comparator group. Hazard ratios for mortality were 0.76 (95% CI; 0.51, 1.12) over 7 days, 0.97 (95% CI; 0.77, 1.21) over 30 days, and 0.91 (95% CI; 0.82, 1.02) over 1 year of follow-up. There was no significant difference in survival or hospital length of stay between nitrate and non-nitrate controls in extended follow-up. There was also no significant effect of nitrates in subgroups stratified by presence of chest pain, troponin elevation, chronic nitrate use, and known coronary artery disease. CONCLUSIONS: In acute decompensated heart failure, use of nitrates acutely in the emergency department setting was not associated with improvement in short-term or near-term survival. Our study does not support generalized use of nitrates when the primary goal of therapy is to reduce mortality. PMID- 26873687 TI - Primary Prevention Implantable Cardioverter Defibrillator (ICD) Therapy in Women Data From a Multicenter French Registry. AB - BACKGROUND: There are limited data describing sex specificities regarding implantable cardioverter defibrillators (ICDs) in the real-world European setting. METHODS AND RESULTS: Using a large multicenter cohort of consecutive patients referred for ICD implantation for primary prevention (2002-2012), in ischemic and nonischemic cardiomyopathy, we examined the sex differences in subjects' characteristics and outcomes. Of 5539 patients, only 837 (15.1%) were women and 53.8% received cardiac resynchronization therapy. Compared to men, women presented a significantly higher proportion of nonischemic cardiomyopathy (60.2% versus 36.2%, P<0.001), wider QRS complex width (QRS >120 ms: 74.6% versus 68.5%, P=0.003), higher New York Heart Association functional class (>=III in 54.2%? versus 47.8%?, P=0.014), and lower prevalence of atrial fibrillation (18.7% versus 24.9%, P<0.001). During a 16 786 patient-years follow-up, overall, fewer appropriate therapies were observed in women (hazard ratio=0.59, 95% CI 0.45-0.76; P<0.001). By contrast, no sex-specific interaction was observed for inappropriate shocks (odds ratio ?=0.84, 95% CI 0.50-1.39, P=0.492), early complications (odds ratio=1.00, 95% CI 0.75-1.32, P=0.992), and all-cause mortality (hazard ratio=0.87 95% CI 0.66-1.15, P=0.324). Analysis of sex-by- cardiac resynchronization therapy interaction shows than female cardiac resynchronization therapy recipients experienced fewer appropriate therapies than men (hazard ratio=0.62, 95% CI 0.50-0.77; P<0.001) and lower mortality (hazard ratio=0.68, 95% CI 0.47-0.97; P=0.034). CONCLUSIONS: In our real-life registry, women account for the minority of ICD recipients and presented with a different clinical profile. Whereas female cardiac resynchronization therapy recipients had a lower incidence of appropriate ICD therapies and all-cause death than their male counterparts, the observed rates of inappropriate shocks and early complications in all ICD recipients were comparable. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01992458. PMID- 26873688 TI - Incidence and Costs Related to Lead Damage Occurring Within the First Year After a Cardiac Implantable Electronic Device Replacement Procedure. AB - BACKGROUND: Inadvertent damage to leads for transvenous pacemakers, implantable cardioverter-defibrillators, and cardiac resynchronization therapy defibrillators is an important complication associated with generator-replacement procedures. We sought to estimate the incidence and costs associated with transvenous lead damage following cardiac implantable electronic device replacement. METHODS AND RESULTS: Using the Truven Health Analytics MarketScan Commercial Research Database, we identified health care claims between 2009 and 2013 for lead damage following generator replacement. Patients were identified by claims with a procedure code for cardiac implantable electronic device replacement and then evaluated for 1 year. All follow-up visits for lead damage were identified, and incidence, risk factors, and hospitalization costs were determined. A total of 22 557 patients with pacemakers, 20 632 with implantable cardioverter defibrillators, and 2063 with cardiac resynchronization therapy defibrillators met selection criteria. Incidence of lead damage was 0.46% for pacemaker replacement, 1.27% for implantable cardioverter-defibrillator replacement, and 1.94% for cardiac resynchronization therapy defibrillator replacement procedures (P<0.001). After adjusting for patient characteristics, patients with implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators demonstrated risk of lead damage that was, respectively, double (hazard ratio 2.00, 95% CI 1.57-2.55) and >2.5 times (hazard ratio 2.58, 95% CI 1.73-3.83) that of patients with pacemakers. Lead revision or repair procedures were associated with increased inpatient hospitalization costs (mean $19 959 for pacemaker, $24 885 for implantable cardioverter-defibrillator, and $46 229 for cardiac resynchronization therapy defibrillator; P=0.048, Kruskal-Wallis test). CONCLUSIONS: These findings establish the first objective assessment of the incidence, risk factors, and economic burden of lead damage following cardiac implantable electronic device replacement in the United States. New care algorithms are warranted to avoid these events, which impose substantial burdens on patients, physicians, and payors. PMID- 26873689 TI - Percutaneous Patent Ductus Arteriosus (PDA) Closure in Very Preterm Infants: Feasibility and Complications. AB - BACKGROUND: Percutaneous closure of patent ductus arteriosus (PDA) in term neonates is established, but data regarding outcomes in infants born very preterm (<32 weeks of gestation) are minimal, and no published criteria exist establishing a minimal weight of 4 kg as a suitable cutoff. We sought to analyze outcomes of percutaneous PDA occlusion in infants born very preterm and referred for PDA closure at weights <4 kg. METHODS AND RESULTS: Retrospective analysis (January 2005-January 2014) was done at a single pediatric center. Procedural successes and adverse events were recorded. Markers of respiratory status (need for mechanical ventilation) were determined, with comparisons made before and after catheterization. A total of 52 very preterm infants with a median procedural weight of 2.9 kg (range 1.2-3.9 kg) underwent attempted PDA closure. Twenty-five percent (13/52) of infants were <2.5 kg. Successful device placement was achieved in 46/52 (88%) of infants. An adverse event occurred in 33% of cases, with an acute arterial injury the most common complication. We observed no association between weight at time of procedure and the risk of an adverse event. No deaths were attributable to the PDA closure. Compared to precatheterization trends, percutaneous PDA closure resulted in improved respiratory status, including less exposure to mechanical ventilation (mixed effects logistic model, P<0.01). CONCLUSIONS: Among infants born very preterm, percutaneous PDA closure at weights <4 kg is generally safe and may improve respiratory health, but risk of arterial injury is noteworthy. Randomized clinical trials are needed to assess clinically relevant differences in outcomes following percutaneous PDA closure versus alternative (surgical ligation) management strategies. PMID- 26873691 TI - Dietary alpha-Linolenic Acid, Marine omega-3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvencion con DIeta MEDiterranea (PREDIMED) Study. PMID- 26873690 TI - Pacemakers as Atrial Fibrillation Detectors: Finding Racial Differences and Opportunities for Preventing Stroke. PMID- 26873692 TI - ABCA1-Mediated Cholesterol Efflux Capacity to Cerebrospinal Fluid Is Reduced in Patients With Mild Cognitive Impairment and Alzheimer's Disease. AB - BACKGROUND: Animal and human studies indicate that ABCA1-mediated cholesterol transport is important in Alzheimer's disease (AD). We hypothesized that the efficiency of cerebrospinal fluid (CSF) to facilitate ABCA1-mediated cholesterol efflux would be reduced in participants with mild cognitive impairment (MCI) or AD compared with cognitively healthy participants. METHODS AND RESULTS: CSF was collected from a cross-sectional study of cognitively healthy participants (n=47) and participants with MCI (n=35) or probable AD (n=26).The capacity of CSF to mediate cholesterol transport was assessed using a BHK cell line that can be induced to express the ABCA1 transporter. ABCA1-mediated cholesterol efflux capacity was 30% less in participants with MCI or AD compared with cognitively healthy participants (P<0.001 for both). Cholesterol efflux capacity correlated with CSF cholesterol content (r=0.37, P<0.001). CSF phosphatidylcholine decreased in participants with MCI and AD compared with cognitively healthy participants (9% less in MCI and 27% less in AD compared with cognitively healthy participants, P=0.01) and correlated with CSF efflux capacity (r=0.3, P=0.001). CSF sphingomyelin also correlated with the efflux capacity (r=0.24, P=0.02). Concentrations of CSF apoA-I and apoE did not significantly correlate with measures of efflux capacity. CONCLUSIONS: In people with MCI and AD, the capacity of CSF to facilitate ABCA1-mediated cholesterol efflux is impaired. This lesser cholesterol efflux in MCI supports a pathophysiological role for ABCA1-mediated cholesterol transport in early neurodegeneration. PMID- 26873693 TI - Adherence to Antihypertensive Medication in Treatment-Resistant Hypertension Undergoing Renal Denervation. AB - BACKGROUND: Adherence to medication has been repeatedly proposed to represent a major cause of treatment-resistant hypertension (TRH); however, treatment decisions such as treating TRH with renal denervation depend on accurate judgment of adherence. We carefully analyzed adherence rates to medication before and after renal denervation and its effect on blood pressure (BP) control. METHODS AND RESULTS: Eighty patients with TRH were included in 2 prospective observational studies that assessed the difference of potential antihypertensive and nephroprotective effects of renal denervation. To compare prescribed with actual medication intake (representing a measure of adherence), we analyzed urine samples collected at baseline and at 6 months after renal denervation for antihypertensive compounds or metabolites (by liquid chromatography-mass spectrometry). In addition to office BP, 24-hour ambulatory BP and central hemodynamics (central systolic pressure, central pulse pressure) were assessed. Informed consent for analyses of urine metabolites was obtained from 79 of 80 patients. Actual intake of all antihypertensive drugs was detected at baseline and at 6 months after renal denervation in 44 (56%) and 52 (66%) patients, respectively; 1 drug was missing in 22 (28%) and 17 (22%) patients, respectively, and >=2 drugs were missing in 13 (16%) and 10 (13%) patients, respectively. At baseline, 24-hour ambulatory BP (P=0.049) and central systolic BP (P=0.012) were higher in nonadherent patients. Adherence did not significantly change overall (McNemar-Bowker test, P=0.362). An increase in adherence was observed in 21 patients, and a decrease was observed in 11 patients. The decrease in 24-hour ambulatory BP was not different in those with stable adherence 6 months after renal denervation (n=41, -7+/-13 mm Hg) compared with those with increased adherence (n=21, -10+/-13 mm Hg) and decreased adherence (n=11, -7+/-14 mm Hg) (P>0.20). Our study is limited by the relatively small sample size and potentially by the specific health environment of our university center (Northern Bavaria, Germany). CONCLUSIONS: Nonadherence to medication among patients with TRH was relatively low: ~1 of 6 patients with TRH did not take >=2 of the prescribed drugs. Adherence pattern did not change significantly after renal denervation and had no impact on the overall observed BP changes, supporting the concept that renal denervation is an effective treatment in patients with TRH. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00888433, NCT01442883 and NCT01687725. PMID- 26873694 TI - Effects of receptor for advanced glycation endproducts on microvessel formation in endometrial cancer. AB - BACKGROUND: The receptor for advanced glycation endproducts (RAGE) and microvascular status both play a critical role in cancer progression. However, the crosstalk between RAGE and microvascular formation in endometrial cancer remains largely unknown. METHODS: RAGE expression and microvessel density were examined in 20 cases of normal endometrial tissue, 37 cases of well differentiated endometrial cancer tissue, and 35 cases of poorly-differentiated endometrial cancer tissue. Regression analysis was used to examine the relationship between RAGE and microvessel density. The knockdown of RAGE was achieved using a small interfering RNA in HEC-1A endometrial cancer cells. A xenografted tumour model was used to evaluate RAGE-mediated microvascular formation and proliferation of endometrial cancer cells. RESULTS: It was shown that (i) RAGE expression gradually increased in normal endometrium, well differentiated endometrial cancer, and poorly-differentiated endometrial cancer, respectively; (ii) a positive correlation existed between RAGE and microvessel density in human endometrial cancer samples; (iii) RAGE knockdown was effective in decreasing microvessel formation in xenografted tumour models; and (iv) RAGE knockdown can significantly inhibit the proliferation of endometrial cancer cells in vivo. CONCLUSIONS: These results indicate that RAGE may be a potential trigger in microvascular formation and proliferation in the development of endometrial cancer. PMID- 26873696 TI - Halomonas urumqiensis sp. nov., a moderately halophilic bacterium isolated from a saline-alkaline lake. AB - A moderately halophilic, aerobic bacterium, strain BZ-SZ-XJ27T, belonging to the genus Halomonas, was isolated from a saline-alkaline lake in the Xinjiang Uyghur Autonomous Region of China. Phylogenetic analysis based on 16S rRNA gene sequences and a multilocus sequence analysis using the 16S rRNA, gyrB and rpoD genes demonstrated that strain BZ-SZ-XJ27T represents a member of the genus Halomonas. On the basis of 16S rRNA gene sequence similarity, the closest relatives were Halomonas campaniensis 5AGT, H. fontilapidosi 5CRT, H. korlensis XK1T and H. sinaiensis ALO SharmT, with similarities of 96.2-97.2 %. DNA-DNA hybridization with H. korlensis CGMCC 1.6981T (the nearest phylogenetic neighbour) and H. campaniensis DSM 15293T (the highest 16S rRNA gene sequence similarity) showed relatedness values of 53 and 38 %, respectively, demonstrating the separateness of the three taxa. The bacterium stained Gram-negative and the cells were motile and rod-shaped. The strain formed creamy-white colonies and grew under optimal conditions of 1.42 M Na+ (range 0.22-4.32 M Na+), pH 8.0-8.5 (range pH 6.0-10.0) and 39 degrees C (range 4-43 degrees C). The dominant fatty acids were summed feature 8 (C18 : 1omega7c/C18 : 1omega6c; 36.6 %), C16 : 0 (25.9 %) and summed feature 3 (C16 : 1omega7c/C16 : 1omega6c; 21.2 %). The dominant polar lipids were two unknown phospholipids, phosphatidylethanolamine and phosphatidylglycerol, and the main respiratory quinones were ubiquinone 9 (Q 9; 89 %) and ubiquinone 8 (Q-8; 10 %). The genomic DNA G+C content was 61.7 +/- 0.8 mol% (Tm). On the basis of phenotypic, chemotaxonomic and phylogenetic features, strain BZ-SZ-XJ27T is proposed to represent a novel species, Halomonas urumqiensis sp. nov., within the genus Halomonas of the family Halomonadaceae. The type strain is BZ-SZ-XJ27T ( = JCM 30202T = CGMCC 1.12917T). PMID- 26873695 TI - Surgically modifiable factors measured by computer-navigation together with patient-specific factors predict knee society score after total knee arthroplasty. AB - BACKGROUND: The purpose was to investigate whether patient-specific factors (PSF) and surgically modifiable factors (SMF), measured by means of a computer-assisted navigation system, can predict the Knee Society Scores (KSS) after total knee arthroplasty (TKA). METHODS: Data from 99 patients collected during a randomized clinical trial were used for this secondary data analysis. The KSS scores of the patients were measured preoperatively and at 4-years follow-up. Multiple regression analyses were performed to investigate which combination of variables would be the best to predict the 4-years KSS scores. RESULTS: When considering SMF alone the combination of four of them significantly predicted the 4-years KSS F score (p = 0.009), explaining 18 % of its variation. When considering only PSF the combination of age and body weight significantly predicted the 4-years KSS-F (p = 0.008), explaining 11 % of its variation. When considering both groups of predictors simultaneously the combination of three PSF and two SMF significantly predicted the 4-years KSS-F (p = 0.007), explaining 20 % of its variation. CONCLUSIONS: Younger age, better preoperative KSS-F scores and lower BMI before surgery, a positive tibial component slope and small changes in femoral offset were predictors of better KSS-F scores at 4-years. PMID- 26873697 TI - Recent advances in actinorhizal symbiosis signaling. AB - Nitrogen and phosphorus availability are frequent limiting factors in plant growth and development. Certain bacteria and fungi form root endosymbiotic relationships with plants enabling them to exploit atmospheric nitrogen and soil phosphorus. The relationships between bacteria and plants include nitrogen-fixing Gram-negative proteobacteria called rhizobia that are able to interact with most leguminous plants (Fabaceae) but also with the non-legume Parasponia (Cannabaceae), and actinobacteria Frankia, which are able to interact with about 260 species collectively called actinorhizal plants. Fungi involved in the relationship with plants include Glomeromycota that form an arbuscular mycorrhizal (AM) association intracellularly within the roots of more than 80% of land plants. Increasing numbers of reports suggest that the rhizobial association with legumes has recycled part of the ancestral program used by most plants to interact with AM fungi. This review focuses on the most recent progress made in plant genetic control of root nodulation that occurs in non-legume actinorhizal plant species. PMID- 26873698 TI - A residue substitution in the plastid ribosomal protein L12/AL1 produces defective plastid ribosome and causes early seedling lethality in rice. AB - The plastid ribosome is essential for chloroplast biogenesis as well as seedling formation. As the plastid ribosome closely resembles the prokaryotic 70S ribosome, many plastid ribosomal proteins (PRPs) have been identified in higher plants. However, their assembly in the chloroplast ribosome in rice remains unclear. In the present study, we identified a novel rice mutant, albino lethal 1 (al1), from a chromosome segment substitution line population. The al1 mutant displayed an albino phenotype at the seedling stage and did not survive past the three-leaf stage. No other apparent differences in plant morphology were observed in the al1 mutant. The albino phenotype of the al1 mutant was associated with decreased chlorophyll content and abnormal chloroplast morphology. Using fine mapping, AL1 was shown to encode the PRPL12, a protein localized in the chloroplasts of rice, and a spontaneous single-nucleotide mutation (C/T), resulting in a residue substitution from leucine in AL1 to phenylalanine in al1, was found to be responsible for the early seedling lethality. This point mutation is located at the L10 interface feature of the L12/AL1 protein. Yeast two-hybrid analysis showed that there was no physical interaction between al1 and PRPL10. In addition, the mutation had little effect on the transcript abundance of al1, but had a remarkable effect on the protein abundance of al1 and transcript abundance of chloroplast biogenesis-related and photosynthesis-related genes. These results provide a first glimpse into the molecular details of L12's function in rice. PMID- 26873699 TI - Differential growth responses of Brachypodium distachyon genotypes to inoculation with plant growth promoting rhizobacteria. AB - Plant growth promoting rhizobacteria (PGPR) can associate and enhance the growth of important crop grasses. However, in most cases, the molecular mechanisms responsible for growth promotion are not known. Such research could benefit by the adoption of a grass model species that showed a positive response to bacterial inoculation and was amenable to genetic and molecular research methods. In this work we inoculated different genotypes of the model grass Brachypodium distachyon with two, well-characterized PGPR bacteria, Azospirillum brasilense and Herbaspirillum seropedicae, and evaluated the growth response. Plants were grown in soil under no nitrogen or with low nitrogen (i.e., 0.5 mM KNO3). A variety of growth parameters (e.g., shoot height, root length, number of lateral roots, fresh and dry weight) were measured 35 days after inoculation. The data indicate that plant genotype plays a very important role in determining the plant response to PGPR inoculation. A positive growth response was observed with only four genotypes grown under no nitrogen and three genotypes tested under low nitrogen. However, in contrast, relatively good root colonization was seen with most genotypes, as measured by drop plate counting and direct, microscopic examination of roots. In particular, the endophytic bacteria H. seropedicae showed strong epiphytic and endophytic colonization of roots. PMID- 26873701 TI - Erratum to: Variations in Performance of Mental Health Providers in the English NHS: An Analysis of the Relationship Between Readmission Rates and Length-of Stay. PMID- 26873700 TI - Fake anti-malarials: start with the facts. AB - This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting. PMID- 26873702 TI - [Development of serous retinopathy during therapy of a metastatic cutaneous melanoma]. AB - Inhibitors of the mitogen-activated protein kinase (MAPK) signal pathway have decisively improved the prognosis of metastatic cutaneous melanoma in patients with an activating mutation in position V600 of the BRAF gene. We report on a patient who was regularly examined in our clinic while participating in a randomized blinded clinical trial. The aim of this trial was to examine the effectiveness and tolerability of a combination of the BRAF inhibitor dabrafenib and the MAPK kinase (MEK) inhibitor trametinib compared with a monotherapy with dabrafenib (plus placebo). During therapy the patient developed a diffuse neuroretinal detachment which could not be completely reversed after discontinuation of the study medication. PMID- 26873703 TI - Habenula volume increases with disease severity in unmedicated major depressive disorder as revealed by 7T MRI. AB - The habenula is a paired epithalamic structure involved in the pathogenesis of major depressive disorder (MDD). Evidence comes from its impact on the regulation of serotonergic and dopaminergic neurons, the role in emotional processing and studies on animal models of depression. The present study investigated habenula volumes in 20 unmedicated and 20 medicated MDD patients and 20 healthy controls for the first time by applying a triplanar segmentation algorithm on 7 Tesla magnetic resonance (MR) whole-brain T1 maps. The hypothesis of a right-side decrease of habenula volumes in the MDD patients was tested, and the relationship between volumetric abnormalities and disease severity was exploratively investigated. Absolute and relative total and hemispheric habenula volumes did not differ significantly between the three groups. In the patients with short duration of disease for which medication effects could be ruled out, significant correlations were found between bilateral habenula volumes and HAMD-17- and BDI II-related severities. In the medicated patients, this positive relationship disappeared. Our findings suggest an involvement of habenula pathology in the beginning of MDD, while general effects independent of severity or stage of disease did not occur. Our findings warrant future combined tractographic and functional investigation using ultra-high-resolution in vivo MR imaging. PMID- 26873705 TI - Heterologous production of the stain solving peptidase PPP1 from Pleurotus pulmonarius. AB - A novel stain solving subtilisin-like peptidase (PPP1) was identified from the culture supernatant of the agaricomycete Pleurotus pulmonarius. It was purified to homogeneity using a sequence of preparative isoelectric focusing, anion exchange and size exclusion chromatography. Peptides were identified by ab initio sequencing (nLC-ESI-QTOF-MS/MS), characterizing the enzyme as a member of the subtilase family (EC 3.4.21.X). An expression system was established featuring the pPIC9K vector, an alternative Kozak sequence, the codon optimized gene ppp1 gene without the native signal sequence with C-terminal hexa-histidine tag, and Pichia pastoris GS115 as expression host. Intracellular active enzyme was obtained from cultivations in shake flasks and in a five liter bioreactor. With reaction optima of 40 degrees C and a pH > 8.5, considerable bleaching of pre stained fabrics (blood, milk and India ink), and the possibility of larger-scale production, the heterologous enzyme is well suitable for detergent applications, especially at lower temperatures as part of a more energy- and cost-efficient washing process. Showing little sequence similarity to other subtilases, this unique peptidase is the first subtilisin-like peptidase from Basidiomycota, which has been functionally produced in Pichia pastoris. PMID- 26873704 TI - Synteny and comparative analysis of miRNA retention, conservation, and structure across Brassicaceae reveals lineage- and sub-genome-specific changes. AB - The recent availability of genome sequences together with syntenic block information for Brassicaceae offers an opportunity to study microRNA (miRNA) evolution across this family. We employed a synteny-based comparative genomics strategy to unambiguously identify miRNA homologs from the genome sequence of members of Brassicaceae. Such an analysis of miRNA across Brassicaceae allowed us to classify miRNAs as conserved, lineage-, karyotype- and sub-genome-specific. The differential loss of miRNA from sub-genomes in polyploid genomes of Brassica rapa and Brassica oleracea shows that miRNA also follows the rules of gene fractionation as observed in the case of protein-coding genes. The study of mature and miR* region of precursors revealed instances of in-dels and SNPs which reflect the evolutionary history of the genomes. High level of conservation in miR* regions in some cases points to their functional relevance which needs to be further investigated. We further show that sequence and length variability in precursor sequences can affect the free energy and foldback structure of miRNA which may ultimately affect their biogenesis and expression in the biological system. PMID- 26873706 TI - Specific light uptake rates can enhance astaxanthin productivity in Haematococcus lacustris. AB - Lumostatic operation was applied for efficient astaxanthin production in autotrophic Haematococcus lacustris cultures using 0.4-L bubble column photobioreactors. The lumostatic operation in this study was performed with three different specific light uptake rates (q(e)) based on cell concentration, cell projection area, and fresh weight as one-, two- and three-dimensional characteristics values, respectively. The q(e) value from the cell concentration (q(e1D)) obtained was 13.5 * 10-8 MUE cell-1 s-1, and the maximum astaxanthin concentration was increased to 150 % compared to that of a control with constant light intensity. The other optimum q e values by cell projection area (q(e2D)) and fresh weight (q( e3D)) were determined to be 195 MUE m-2 s-1 and 10.5 MUE g-1 s-1 for astaxanthin production, respectively. The maximum astaxanthin production from the lumostatic cultures using the parameters controlled by cell projection area (2D) and fresh weight (3D) also increased by 36 and 22% over that of the controls, respectively. When comparing the optimal q e values among the three different types, the lumostatic cultures using q(e) based on fresh weight showed the highest astaxanthin productivity (22.8 mg L-1 day-1), which was a higher level than previously reported. The lumostatic operations reported here demonstrated that more efficient and effective astaxanthin production was obtained by H. lacustris than providing a constant light intensity, regardless of which parameter is used to calculate the specific light uptake rate. PMID- 26873707 TI - Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1. AB - The elevation of bradykinin (BK) level during attacks of hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) is well known. We previously demonstrated that endothelin-1 (ET-1) level also increases during C1-INH-HAE attacks. Although BK and ET-1 are both potent vasoactive peptides, the vasoregulatory aspect of the pathomechanism of C1-INH-HAE has not yet been investigated. Hence we studied the levels of vasoactive peptides in controls and in C1-INH-HAE patients, as well as evaluated their changes during C1-INH-HAE attacks. The levels of arginine vasopressin (AVP), adrenomedullin (ADM) and ET-1 were measured in the plasma of 100 C1-INH-HAE patients in inter-attack periods and of 111 control subjects, using BRAHMS Kryptor technologies. In 18 of the 100 C1-INH-HAE patients, the levels of vasoactive peptides were compared in blood samples obtained during attacks, or in inter-attack periods. AVP, ADM and ET-1 levels were similar in inter-attack samples from C1-INH-HAE patients and in the samples of controls, although cardiovascular risk has an effect on the levels of vasoactive peptides in both groups. The levels of all three vasoactive peptides increased during C1-INH-HAE attacks. Moreover, the levels of ET-1 and ADM as well as their changes during attacks were significantly correlated. This study demonstrated that vascular regulation by vasoactive peptides is affected during C1-INH-HAE attacks. Our results suggest that the cooperation of several vasoactive peptides may be necessary to counterbalance the actions of excess BK, and to terminate the attacks. This may reveal a novel pathophysiological aspect of C1-INH-HAE. PMID- 26873709 TI - Margaret McCartney: Pity the NHS--Jeremy Hunt has chosen the nuclear option. PMID- 26873708 TI - Life with a Primary Immune Deficiency: a Systematic Synthesis of the Literature and Proposed Research Agenda. AB - PURPOSE: The clinical immunology literature is punctuated with research on psychosocial dimensions of illness. Studies investigating the lived experiences and stated needs of patients with primary immune deficiencies and their families are essential to improving clinical management and determining the research questions that matter to patients and other stakeholders. Yet, to move the field forward, a systematic review of literature and proposed agenda is needed. METHODS: A systematic review was conducted via PubMed and Scopus to include original research on psychological, social, or behavioral aspects of primary immune deficiencies published between 1999 and 2015. A Title/Abstract keyword search was conducted, 317 candidate article abstracts were manually reviewed, and forward/backward reference searches were completed. RESULTS: Twenty-nine studies met inclusion criteria. These illuminate the complex psychological, social, and emotional experiences of primary immune deficiency. Themes included the potential for negative psychosocial impact from disease; adaptation over time; the multi dimensional assessments of quality of life; familial impact; the important roles of hope, developing a sense of control, social support; and addressing anxiety/depression in our patients and their families. Methodological considerations and areas for improvement are discussed. CONCLUSION: We propose the research agenda focus on study creativity and rigor, with improved engagement with existing literature and critical study design (e.g., methodology with adequate statistical power, careful variable selection, etc.). This review highlights opportunities to advance psychosocial research and bring a brighter future to clinicians, researchers, and families affected by primary immune deficiency. PMID- 26873710 TI - Biomechanical evaluation of medial patello-femoral ligament reconstruction: comparison between a double-bundle converging tunnels technique versus a single bundle technique. AB - BACKGROUND: Several MPFL reconstructions are commonly performed for recurrent patellar dislocation, but misleading data are currently available in the literature on the ability of the different techniques to re-create a functioning ligament. MATERIALS AND METHODS: In this study, we showed the biomechanical properties of two different procedures for MPFL reconstruction using a natural orientation during uniaxial tensile testing. Eighteen fresh-frozen human knees were randomly assigned to two groups of nine each. In the group A, the reconstruction was performed using a double converging tunnels technique and in the group B was used a single-tunnel technique with semitendinosus autograft. The specimens were loaded in natural orientation using an Instron tensile test machine, and the stiffness and ultimate load were determined. RESULTS: The ultimate load was 213 +/- 90 and 171 +/- 51 N using our double-bundle technique (group A) and the single-bundle technique (group B), respectively. One (11 %) specimen failed at the patellar side due to patellar fracture in the group B. There was no statistical significant difference (p > 0.05) between the two groups in terms of stiffness and ultimate load. CONCLUSION: This study is the first biomechanical evaluation of the MPFL reconstructions in natural orientation. Both the procedures achieved safe fixation of the graft at the femoral attachment; however, the single-bundle technique reported 11 % of failure at the patellar side due to patellar fracture. In addition, the double-bundle technique can better restore the anatomy of the native ligament. PMID- 26873711 TI - COMPARISON OF ADAPTIVE STATISTICAL ITERATIVE RECONSTRUCTION (ASIRTM) AND MODEL BASED ITERATIVE RECONSTRUCTION (VEOTM) FOR PAEDIATRIC ABDOMINAL CT EXAMINATIONS: AN OBSERVER PERFORMANCE STUDY OF DIAGNOSTIC IMAGE QUALITY. AB - The diagnostic image quality of 75 paediatric abdominal computed tomography (CT) examinations reconstructed with two different iterative reconstruction (IR) algorithms-adaptive statistical IR (ASiRTM) and model-based IR (VeoTM)-was compared. Axial and coronal images were reconstructed with 70 % ASiR with the SoftTM convolution kernel and with the Veo algorithm. The thickness of the reconstructed images was 2.5 or 5 mm depending on the scanning protocol used. Four radiologists graded the delineation of six abdominal structures and the diagnostic usefulness of the image quality. The Veo reconstruction significantly improved the visibility of most of the structures compared with ASiR in all subgroups of images. For coronal images, the Veo reconstruction resulted in significantly improved ratings of the diagnostic use of the image quality compared with the ASiR reconstruction. This was not seen for the axial images. The greatest improvement using Veo reconstruction was observed for the 2.5 mm coronal slices. PMID- 26873712 TI - THE EFFECT OF ADAPTIVE STATISTICAL ITERATIVE RECONSTRUCTION ON THE ASSESSMENT OF DIAGNOSTIC IMAGE QUALITY AND VISUALISATION OF ANATOMICAL STRUCTURES IN PAEDIATRIC CEREBRAL CT EXAMINATIONS. AB - The purpose of this study was to investigate the effect of adaptive statistical iterative reconstruction (ASiR) on the visualisation of anatomical structures and diagnostic image quality in paediatric cerebral computed tomography (CT) examinations. Forty paediatric patients undergoing routine cerebral CT were included in the study. The raw data from CT scans were reconstructed into stacks of 5 mm thick axial images at various levels of ASiR. Three paediatric radiologists rated six questions related to the visualisation of anatomical structures and one question on diagnostic image quality, in a blinded randomised visual grading study. The evaluated anatomical structures demonstrated enhanced visibility with increasing level of ASiR, apart from the cerebrospinal fluid space around the brain. In this study, 60 % ASiR was found to be the optimal level of ASiR for paediatric cerebral CT examinations. This shows that the commonly used 30 % ASiR may not always be the optimal level. PMID- 26873714 TI - MRI features have a role in pre-surgical planning of colloid cyst removal. AB - BACKGROUND: Endoscopic resection is becoming a well-established treatment option for patients with colloid cysts of the third ventricle. A disadvantage of this approach is the decreased ability to resect cysts in their entirety. Correlations between magnetic resonance imaging (MRI) features and cyst content could potentially help surgeons decide on the extent of resection and approach. We attempted to identify a correlation between patients' MRI imaging patterns and difficult cyst removal, post-operative adverse outcomes and the need for cerebrospinal fluid (CSF) diversion, in order to detect markers that may affect pre-surgical planning. METHOD: A retrospective examination of all patients' records that underwent a colloid cyst excision attempt at our institution between 2001 and 2014, and which had a minimum 1-year follow-up was compiled. RESULTS: Of the 25 patients fulfilling the criteria, we found cysts with a low T2 signal, specifically when combined with high T1 signal, to be significantly correlated with piecemeal, difficult removals. Correlation was also found between high T2 signal cysts and pre-operative hydrocephalus. Among patients that had pre existing hydrocephalus, those that required a piecemeal removal possessed a strong trend towards a need for subsequent shunting. CONCLUSIONS: We found specific MRI features suggestive of difficult cyst excision. In a subgroup of patients with pre-operative hydrocephalus and imaging features suggestive of difficult removal, significantly higher rates of shunting were observed. We therefore recommend an open approach in cases of low T2, high T1 signal cysts with a diameter of over 15 mm, or CSF shunting in poor surgical candidates. Smaller cysts, with a low T1 signal, a high T2 signal and pre-operative hydrocephalus, constitute a subgroup in which we recommend endoscopic intervention as the procedure of choice. PMID- 26873713 TI - Identifying the effect of patient sharing on between-hospital genetic differentiation of methicillin-resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common healthcare-associated pathogens. To examine the role of inter-hospital patient sharing on MRSA transmission, a previous study collected 2,214 samples from 30 hospitals in Orange County, California and showed by spa typing that genetic differentiation decreased significantly with increased patient sharing. In the current study, we focused on the 986 samples with spa type t008 from the same population. METHODS: We used genome sequencing to determine the effect of patient sharing on genetic differentiation between hospitals. Genetic differentiation was measured by between-hospital genetic diversity, F ST , and the proportion of nearly identical isolates between hospitals. RESULTS: Surprisingly, we found very similar genetic diversity within and between hospitals, and no significant association between patient sharing and genetic differentiation measured by F ST . However, in contrast to F ST , there was a significant association between patient sharing and the proportion of nearly identical isolates between hospitals. We propose that the proportion of nearly identical isolates is more powerful at determining transmission dynamics than traditional estimators of genetic differentiation (F ST ) when gene flow between populations is high, since it is more responsive to recent transmission events. Our hypothesis was supported by the results from coalescent simulations. CONCLUSIONS: Our results suggested that there was a high level of gene flow between hospitals facilitated by patient sharing, and that the proportion of nearly identical isolates is more sensitive to population structure than F ST when gene flow is high. PMID- 26873715 TI - Demographic distribution of hospital admissions for brain arteriovenous malformations in Germany--estimation of the natural course with the big-data approach. AB - BACKGROUND: Estimation of the natural history of arteriovenous malformations based on short-term observation is potentially biased by multiple factors. Retrieval of demographic information of all AVM patients of national data pools and comparison with the national demographic profile might be another way to approach the natural history. MATERIALS AND METHODS: Upon request, the German Federal Statistical Office provided the numbers of patients admitted in Germany from 2009 through 2013 with ICD Q28.2 (brain AVM) as primary discharge diagnosis, and the corresponding age distribution. Age-related admission rates of AVM were calculated by comparison with the German demographic distribution. RESULTS: A total of 6527 patients were hospitalized from 2009-2013 with brain AVM (Q28.2) as the principal diagnosis. Age-specific admission rate during the first year of life was high with 19.0/100,000 during the 5-year study period, corresponding to a yearly admission rate of 3.8 per 100,000 babies. Apart from the high admission rate during the first year of life, the admission rate was low, but steadily increasing during first decades of life reaching a plateau with 11.1/100,000 in the age group 30-34 years, corresponding to an annual admission rate of 2.2/100,000. After the age of 30-34 years, admission rates decreased continuously, reaching 0 in the age group 90-95 years. The lifetime risk of admission in terms of admission per 100,000 age-matched people was calculated by retrograde integration of the admission rates. At the age of 1 year, the cumulative number of future admissions for AVM during lifetime amounted to 131.3/100,000 children. For the older age groups, the chance of future admission for AVM decreased as expected, reaching 43.8/100,000 by the age of 50 and 0 by the age of 90. CONCLUSIONS: Despite some open issues, the current data suggests that achieving old age with an untreated brain AVM is unlikely. Furthermore, the data support the concept that most brain AVMs are not necessarily a congenital entity but develop during the first decades of life. PMID- 26873716 TI - Giant aggressive chondrosarcoma of the calvarium: a rare entity and its differentials. PMID- 26873717 TI - Genetics of irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) is a common condition with a complex and largely unknown etiology. There is no cure, and treatment options are mainly directed to the amelioration of symptoms. IBS causes reduced quality of life and poses considerable repercussions on health and socioeconomic systems. There is a heritable component in IBS, and genetic research is a valuable tool for the identification of causative pathways, which will provide important insight into the pathophysiology. However, although some gene-hunting efforts have been conducted and a few risk genes proposed, IBS genetic research is lagging behind compared to other complex diseases. In this mini-review, we briefly summarize existing genetic studies, discuss the main challenges in IBS genetic research, and propose strategies to overcome these challenges for IBS gene discovery. PMID- 26873718 TI - Update on Lynch syndrome genomics. AB - Four main DNA mismatch repair (MMR) genes have been identified, MLH1, MSH2, MSH6, and PMS2, which when mutated cause susceptibility to Lynch syndrome (LS). LS is one of the most prevalent hereditary cancer syndromes in man and accounts for 1-3 % of unselected colorectal carcinomas and some 15 % of those with microsatellite instability and/or absent MMR protein. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) maintains a database for LS associated mutations since 1996. The database was recently reorganized to efficiently gather published and unpublished data and to classify the variants according to a five-tiered scheme linked to clinical recommendations. This review provides an update of germline mutations causing susceptibility to LS based on information available in the InSiGHT database and the latest literature. MMR gene mutation profiles, correlations between genotype and phenotype, and possible mechanisms leading to the characteristic spectrum of tumors in LS are discussed in light of the different functions of MMR proteins, many of which directly serve cancer avoidance. PMID- 26873720 TI - Regulation and registration as drivers of continuous professional competence for Irish pre-hospital practitioners: a discussion paper. AB - BACKGROUND: The regulatory body responsible for the registration of Irish pre hospital practitioners, the Pre-Hospital Emergency Care Council (PHECC), identified the need to implement a continuing professional competence (CPC) framework. The first cycle of CPC (focused on emergency medical technicians) commenced in November 2013 creating for the first time a formal relationship between continuing competence and registration to practice. AIMS: To review current literature and to describe benefits and challenges relevant to CPC, regulation, registration and their respective contributions to professionalism of pre-hospital practitioners: advanced paramedics, paramedics and emergency medical technicians. METHODS: Online search of cumulative index to nursing and allied health literature (CINAHL Plus with Full Text), Allied and Complementary Medicine (AMED) and 'Pubmed' databases using: 'Continuous Professional Development'; 'Continuous Professional Development'; 'emergency medical technician'; 'paramedic'; 'registration'; 'regulation'; and "profession' for relevant articles published since 2004. Additional policy documents, discussion papers, and guidance documents were identified from bibliographies of papers found. RESULTS: Reports, governmental policies for other healthcare professions, and professional developments internationally for allied professions (e.g., nursing, physiotherapy and medicine) link maintenance of competence with requirements for registration to practice. CONCLUSION: We suggest that evolving professionalisation of Irish paramedics should be affirmed through behaviours and competencies that incorporate adherence to professional codes of conduct, reflective practice, and commitment to continuing professional development. While the need for ambulance practitioner CPD was identified in Ireland almost a decade ago, PHECC now has the opportunity to introduce a model of CPD for paramedics linking competence and professionalism to annual registration. PMID- 26873721 TI - 24th Sylvester O'Halloran Perioperative Scientific Symposium. PMID- 26873719 TI - Hereditary cancer syndromes: utilizing DNA repair deficiency as therapeutic target. AB - Human cells have numerous repair mechanisms to counteract various insults incurred on the DNA. Any mutation in these repair mechanisms can lead to accumulation of DNA errors and carcinogenesis. This review aims to discuss the therapeutic options in the two most common DNA repair deficient cancer syndromes, namely Lynch syndrome (hereditary non-polyposis colorectal cancer) and breast cancer susceptibility gene (BRCA) associated ovarian and breast cancer. Deficiency in DNA repair mechanisms renders these tumors with increased sensitivity to platinum agents. There has been increasing amount of information on the utility of the defects in DNA repair as targets for cancer therapy in these syndromes. Novel therapies like poly (ADP-ribose) polymerase (PARP) inhibitors are one of such example where the induction of double stranded breaks in DNA leads to tumoricidal effect in patients with homologous DNA repair deficiency. Interestingly, patients with DNA repair deficiencies tend to have a more favorable prognosis than sporadic malignancies. In microsatellite high colorectal cancer patients, this has been attributed to increased recruitment of CD8+ T lymphocytes in tumor microenvironment. However, these tumors are able to limit the host immune response by activation of immune checkpoints that seem like attractive targets of therapy in the future. PMID- 26873722 TI - Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis. AB - PURPOSE: Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear. METHODS: We undertook a meta analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. RESULTS: Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62-1.13; p = 0.25; I (2) = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35-2.06; p = 0.72; I (2) = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18-1.73; p = 0.32; I (2) = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), -1.78; 95 % CI, -2.31 to 1.24; p < 0.00001; I (2) = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, -2.03 mmHg; 95 % CI, 3.64 to -0.42; p = 0.01; I (2) = 0 %; for diastolic BP: MD, -1.79 mmHg; 95 % CI, 2.89 to -0.68; p = 0.001; I (2) = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke. CONCLUSIONS: CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings. PMID- 26873723 TI - Nutrient Starvation Decreases Cx43 Levels and Limits Intercellular Communication in Primary Bovine Corneal Endothelial Cells. AB - Connexin (Cx) proteins form large conductance channels which function as regulators of communication between neighboring cells via gap junctions and/or hemichannels. Intercellular communication is essential to coordinate cellular responses in tissues and organs, thereby fulfilling an essential role in the spreading of signaling, survival and death processes. Connexin 43 (Cx43), a major connexin isoform in brain and heart, is rapidly turned over. Recent studies implicated that autophagy, a lysosomal degradation pathway induced upon nutrient starvation, mediates connexins, including Cx43, degradation. Here, we examined the impact of nutrient starvation on endogenous Cx43-protein levels and endogenous Cx43-driven intercellular communication in primary bovine corneal endothelial cells (BCECs). Hank's Balanced Salt Solution (HBSS) was used as a starvation condition that induces autophagic flux without impacting the survival of the BCECs. Nutrient starvation of BCECs caused a rapid decline in Cx43-protein levels, both as gap junctions and as hemichannels. The time course of the decline in Cx43-protein levels coincided with the time course of the decline in intercellular communication, assessed as intercellular Ca(2+)-wave propagation in BCECs exposed to a single-cell mechanical stimulus. The decline in Cx43-protein levels, both as gap junctions and as hemichannels, could be prevented by the addition of bafilomycin A1, a lysosomal inhibitor, during the complete nutrient starvation period. Consistent with this, bafilomycin A1 significantly alleviated the decrease in intercellular Ca(2+)-wave propagation. This study further underpins the importance of autophagy as an important degradation pathway for Cx43 proteins during periods of nutrient deprivation, thereby impacting the ability of cells to perform intercellular communication. PMID- 26873724 TI - Rapid Detection of Ricin in Serum Based on Cu-Chelated Magnetic Beads Using Mass Spectrometry. AB - The protein toxin ricin obtained from castor bean plant (Ricinus communis) seeds is a potent biological warfare agent due to its ease of availability and acute toxicity. In this study, we demonstrated a rapid and simple method to detect ricin in serum in vitro. The ricin was mixed with serum and digested by trypsin, then all the peptides were efficiently extracted using Cu-chelated magnetic beads and were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The specific ricin peptides were identified by Nanoscale Ultra Performance liquid chromatography coupled to tandem mass spectrometry according to their sequences. The assay required 2.5 hours, and a characteristic peptide could be detected down to 4 ng/MUl and used as a biomarker to detect ricin in serum. The high sensitivity and simplicity of the procedure makes it valuable in clinical practice. Graphical Abstract ?. PMID- 26873725 TI - Pain and its clinical associations in individuals with cystic fibrosis: A systematic review. AB - Pain is recognized as a clinical complication in cystic fibrosis (CF), but the prevalence, characteristics and clinical associations of this co-morbidity have not been systematically reviewed. Electronic searches of six databases were performed. For inclusion in phase 1, studies reported a pain prevalence rate in CF and/or its clinical associations. For phase 2, included studies reported the measurement properties of validity, reliability and responsiveness of an instrument assessing pain in CF. Two independent reviewers rated the quality of evidence (phase 1) and the measurement properties using the 4-point COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) checklist (phase 2). Of the 400 studies identified in the literature, 16 met the inclusion criteria for phase 1 and 5 for phase 2. The mean (SD) quality score (of 16) was 11.8 (2.3). The pooled prevalence of pain in adults with CF was 77% (95% confidence interval (CI): 57%-92%) and in children was 42% (95% CI: 0%-91%). Common regions of pain included back, abdomen, chest and limbs. In children and adults, pain was associated with a poorer quality of life (QOL) and significant interference with treatments. Measurement properties of three instruments (Brief Pain Inventory, Multidimensional Pain Inventory, Daily Pain Assessment-CF) were construct validity and criterion-predictive validity, with variable findings based on 'fair' to 'good' quality studies. Pain is a common problem in both children and adults with CF. It has negative clinical associations with QOL and the ability to successfully undertake treatment. Further research exploring the measurement properties of instruments assessing pain is required. PMID- 26873727 TI - Precision Oncology: The UC San Diego Moores Cancer Center PREDICT Experience. AB - By profiling their patients' tumors, oncologists now have the option to use molecular results to match patients with drug(s) based on specific biomarkers. In this observational study, 347 patients with solid advanced cancers and next generation sequencing (NGS) results were evaluated. Outcomes for patients who received a "matched" versus "unmatched" therapy following their NGS results were compared. Eighty-seven patients (25%) were treated with a "matched" therapy, 93 (26.8%) with an "unmatched" therapy. More patients in the matched group achieved stable disease (SD) >= 6 months/partial response (PR)/complete response (CR), 34.5% vs. 16.1%, (P <= 0.020 multivariable or propensity score methods). Matched patients had a longer median progression-free survival (PFS; 4.0 vs. 3.0 months, P = 0.039 in the Cox regression model). In analysis using PFS1 (PFS on the prior line of therapy) as a comparator to PFS after NGS, as expected, the unmatched group demonstrated a PFS2 significantly shorter than PFS1 (P = 0.009); however, this shortening was not observed in the matched patients (P = 0.595). Furthermore, 45.3% of the matched patients (24/53) had a PFS2/PFS1 ratio >=1.3 compared with 19.3% of patients (11/57) in the unmatched group (P = 0.004 univariable and P >= 0.057 in multivariable/propensity score analysis). Patients with a "matching-score" (the number of matched drugs divided by the number of aberrations; unmatched patients had a score of zero) > 0.2 had a median overall survival (OS) of 15.7 months compared with 10.6 months when their matching-score was <= 0.2, (P = 0.040 in the Cox regression model). Matched versus unmatched patients had higher rates of SD >= 6 months/PR/CR and longer PFS, and improvement in OS correlated with a higher matching score in multivariable analysis. Mol Cancer Ther; 15(4); 743-52. (c)2016 AACR. PMID- 26873726 TI - Preclinical Evaluation of UAB30 in Pediatric Renal and Hepatic Malignancies. AB - Rare tumors of solid organs remain some of the most difficult pediatric cancers to cure. These difficult tumors include rare pediatric renal malignancies, such as malignant rhabdoid kidney tumors (MRKT) and non-osseous renal Ewing sarcoma, and hepatoblastoma, a pediatric liver tumor that arises from immature liver cells. There are data in adult renal and hepatic malignancies demonstrating the efficacy of retinoid therapy. The investigation of retinoic acid therapy in cancer is not a new strategy, but the widespread adoption of this therapy has been hindered by toxicities. Our laboratory has been investigating a novel synthetic rexinoid, UAB30, which exhibits a more favorable side-effect profile. In this study, we hypothesized that UAB30 would diminish the growth of tumor cells from both rare renal and liver tumors in vitro and in vivo We successfully demonstrated decreased cellular proliferation, invasion and migration, cell-cycle arrest, and increased apoptosis after treatment with UAB30. Additionally, in in vivo murine models of human hepatoblastoma or rare human renal tumors, there were significantly decreased tumor xenograft growth and increased animal survival after UAB30 treatment. UAB30 should be further investigated as a developing therapeutic in these rare and difficult-to-treat pediatric solid organ tumors. Mol Cancer Ther; 15(5); 911-21. (c)2016 AACR. PMID- 26873731 TI - Factors associated with exit block and impact on the emergency department. AB - We used routinely available data to identify the likelihood of exit block within type 1 EDs across acute trusts in England. While the findings are based on exploratory work and should be treated with caution, some patterns appeared to emerge from the data and require further exploration. NHS Trusts at risk of exit block were more likely to be large trusts, located in larger catchment areas, having higher admission rates and inpatient bed occupancy and higher levels of patients leaving the ED without being seen or reattending. Some of the factors identified may well be symptomatic of exit block rather than causal, while other factors may be acting as proxies for differences in casemix, social deprivation or ability to access alternative urgent care services. PMID- 26873730 TI - 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors. AB - There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753-63. (c)2016 AACR. PMID- 26873728 TI - Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics. AB - Constitutively activated STAT3 protein has been found to be a key regulator of pancreatic cancer and a target for molecular therapeutic intervention. In this study, PG-S3-001, a small molecule derived from the SH-4-54 class of STAT3 inhibitors, was found to inhibit patient-derived pancreatic cancer cell proliferation in vitro and in vivo in the low micromolar range. PG-S3-001 binds the STAT3 protein potently, Kd = 324 nmol/L by surface plasmon resonance, and showed no effect in a kinome screen (>100 cancer-relevant kinases). In vitro studies demonstrated potent cell killing as well as inhibition of STAT3 activation in pancreatic cancer cells. To better model the tumor and its microenvironment, we utilized three-dimensional (3D) cultures of patient-derived pancreatic cancer cells in the absence and presence of cancer-associated fibroblasts (CAF). In this coculture model, inhibition of tumor growth is maintained following STAT3 inhibition in the presence of CAFs. Confocal microscopy was used to verify tumor cell death following treatment of 3D cocultures with PG-S3-001. The 3D model was predictive of in vivo efficacy as significant tumor growth inhibition was observed upon administration of PG-S3 001. These studies showed that the inhibition of STAT3 was able to impact the survival of tumor cells in a relevant 3D model, as well as in a xenograft model using patient-derived cells. Mol Cancer Ther; 15(5); 794-805. (c)2016 AACR. PMID- 26873729 TI - High Expression of miR-532-5p, a Tumor Suppressor, Leads to Better Prognosis in Ovarian Cancer Both In Vivo and In Vitro. AB - Ovarian cancer is the leading cause of death for gynecologic cancers, ranking fifth overall for cancer-related death among women. The identification of biomarkers and the elucidation of molecular mechanisms for improving treatment options have received extensive efforts in ovarian cancer research. miRNAs have high potential to act as both ovarian cancer biomarkers and as critical regulators of ovarian tumor behavior. We comprehensively analyzed global mRNA, miRNA expression, and survival data for ovarian cancer from The Cancer Genome Atlas (TCGA) to pinpoint miRNAs that play critical roles in ovarian cancer survival through their effect on mRNA expression. We performed miRNA overexpression and gene knockdown experiments to confirm mechanisms predicted in our bioinformatics approach. We established that overexpression of miR-532-5p in OVCAR-3 cells resulted in a significant decrease in cell viability over a 96-hour time period. In the TCGA ovarian cancer dataset, we found 67 genes whose expression levels were negatively correlated with miR-532-5p expression and correlated with patient survival, such as WNT9A, CSNK2A2, CHD4, and SH3PXD2A The potential miR-532-5p-regulated gene targets were found to be enriched in the Wnt pathway. Overexpression of miR-532-5p through miRNA mimic caused downregulation of CSNK2A2, CHD4, and SH3PXD2A in the OVCAR-3 cell line. We have discovered and validated the tumor-suppressing capabilities of miR-532-5p both in vivo through TCGA analysis and in vitro through ovarian cancer cell lines. Our work highlights the potential clinical importance of miR-532-5p expression in ovarian cancer patients. Mol Cancer Ther; 15(5); 1123-31. (c)2016 AACR. PMID- 26873733 TI - Carbon monoxide poisoning in our homes - report of two survivors from North India. AB - Carbon monoxide poisoning can result from, e.g., the use of unvented coal-burning heaters, indoor barbecues, or inhalation of exhaust of vehicles. The latter is sometimes used to commit suicide. The most common presentation of carbon monoxide poisoning is cerebral hypoxia. Despite frequent use of indoor coal-burning heaters and stoves during winter months in the northern part of India, carbon monoxide poisoning has been infrequently reported. We describe two cases of carbon monoxide poisoning who reported to the Emergency Department in the early morning of a winter season with un-witnessed, unexplained development of altered level of consciousness. PMID- 26873732 TI - Earthworm Preference Bioassays to Evaluate Land Management Practices. AB - Earthworm preference tests, especially in soil-dosed exposures, can be an informative tool for assessing land management practices. Agricultural management intended to increase crop yield and improve soil sustainability includes physical manipulation of topsoil through conventional tillage, reduced or no-tillage, and/or winter cover crops. Soil amendments include the addition of inorganic nitrogen or organic nitrogen derived from soil amendments including biosolids from sewage treatment plants, poultry litter, or locally available industrial effluent. This study used 48-h Eisenia fetida preference tests to assess impacts of agricultural management practices on soil macrofauna. Although in laboratory dosed exposures, E. fetida preferred biosolid-dosed soils (80 %-95 % recovery) over control soils, the same results were not found with field soils receiving biosolid amendments (33 % recovery). Poultry litter-amended soils (68 % recovery) were preferred over control soils. No differences were measured between tilled fields and controls, and earthworms preferred control soils over those from fields with no-tillage and cover crops. Soil assessments through laboratory exposures such as these allows science-based agricultural management decisions to maintain or improve soil health. PMID- 26873734 TI - Investigating death in custody. PMID- 26873735 TI - Allogeneic stem cell transplantation for X-linked agammaglobulinemia using reduced intensity conditioning as a model of the reconstitution of humoral immunity. AB - BACKGROUND: We herein report the first case of X-linked agammaglobulinemia (XLA) that underwent allogeneic stem cell transplantation using reduced intensity conditioning (RIC). We chronologically observed the reconstitution of humoral immunity in this case. CASE PRESENTATION: The patient was a 28-year-old Japanese male with XLA who previously had life-threatening infectious episodes and was referred for the possible indication of allogeneic stem cell transplantation. After a thorough discussion within specialists from different backgrounds, we decided to perform allogeneic peripheral stem cell transplantation from his HLA identical elder brother. Due to the non-malignant nature of XLA, we selected RIC consisting of fludarabine, cyclophosphamide, anti-thymocyte globulin, and 3 Gy of total body irradiation. Neutrophil engraftment was achieved on day 11 with complete donor chimerism. No major complications, except for stage 1 skin graft versus-host disease, were observed. The patient was discharged on day 75 and has been followed as an outpatient without any infectious episodes for more than 500 days. CONCLUSIONS: Regarding immune reconstitution, CD19(+) cells, IgA, and IgM, which were undetectable before allogeneic stem cell transplantation (allo-SCT), started to increase in number 10 days after allo-SCT and continued to increase for more than 1 year. Anti-B antibodies appeared as early as day 10. Total IgG levels decreased after the discontinuation of IgG replacement and spontaneously recovered after day 350. However, most anti-viral IgG titers, except EB virus virus capsid antigen IgG, disappeared after the discontinuation of IgG replacement. A seasonal vaccination to influenza was performed on day 148, with neither anti-influenza type A nor type B being positive after the vaccination. The transient transfer of allergic immunity to orchard grass was observed. Similar Bruton's tyrosine kinase (BTK) expression levels in monocytes and B-cells were observed between the patient and healthy control. B-cells in the peripheral blood (PB) of the patient on day 279 showed sufficient proliferation after a CD40L and IL-21 or CD40L and CpG stimulation. Effective immunoglobulin production and class switching were also observed after a CD40L and IL-21 or CpG stimulation. Signal joint kappa-deleting recombination excision circles (sjKRECs) became positive 16 days post-SCT, increased to 6300 copies/MUg DNA at 42 days, and were maintained at a high level thereafter. The recovery of T-cell receptor excision circles (TRECs) was slow, but became detectable 1 year post hematopoietic stem cell transplantation (HSCT). PMID- 26873737 TI - The Thr to Met substitution of amino acid 118 in hepatitis B virus surface antigen escapes from immune-assay-based screening of blood donors. AB - Hepatitis B surface antigen (HBsAg) is the main diagnosis marker for hepatitis B virus (HBV) infection. In this study, a novel HBV mutant from an HBV-positive blood donor with false-negative results during HBsAg screening was identified. DNA sequencing discovered two mutations at nt 353 (A to T) and nt 349 (T to A), leading to Thr to Met and Ser to Thr substitutions at aa 118 and 117 of HBsAg, respectively. Further analysis showed that eight of ten HBsAg ELISA kits failed to detect this HBsAg mutant. A mutagenesis assay indicated that the Thr to Met substitution at aa 118 was the determinant for escape from HBsAg ELISA detection. A small-scale screening of blood donors identified two individuals infected by this unique HBV mutant, suggesting a certain level of prevalence among the general population. In conclusion, our study identified the aa 118 mutation in HBV surface antigen and provided information for improvement of HBV diagnosis products. PMID- 26873736 TI - A nomogram for predicting the likelihood of lymph node metastasis in early gastric patients. AB - BACKGROUND: Early gastric cancer is defined as a lesion confined to the mucosa or submucosa, regardless of the size or lymph node metastasis. Treatment methods include endoscopic mucosal resection or endoscopic submucosal dissection, wedge resection, laparoscopically assisted gastrectomy and open gastrectomy. Lymph node metastasis is strong related with survival and recurrence. Therefore, the likelihood of lymph node metastasis is one of the most important factors when determining the most appropriate treatment. METHODS: We retrospectively analyzed 597 patients who underwent D2 gastrectomy for early gastric cancer. The relationship between lymph node metastasis and clinicopathological features was analyzed. Using multivariate logistic regression analyses, we created a nomogram to predict the lymph node metastasis probability for early gastric cancer. Receiver operating characteristic analyses was performed to assess the predictive value of the model. RESULTS: In the present study, 58 (9.7%) early gastric cancer patients were histologically shown to have lymph node metastasis. The multivariate logistic regression analysis demonstrated that the age at diagnosis, differentiation status, the presence of ulcers, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in early gastric cancer. Additionally, the tumor macroscopic type, size and histology type significantly correlated with these important independent factors. We constructed a predictive nomogram with these factors for lymph node metastasis in early gastric cancer patients, and the discrimination was good with the AUC of 0.860 (95% CI: 0.809-0.912). CONCLUSIONS: We developed an effective nomogram to predict the incidence of lymph node metastasis for early gastric cancer patients. PMID- 26873738 TI - Probing the nucleotide-binding activity of a redox sensor: two-component regulatory control in chloroplasts. AB - Two-component signal transduction systems mediate adaptation to environmental changes in bacteria, plants, fungi, and protists. Each two-component system consists of a sensor histidine kinase and a response regulator. Chloroplast sensor kinase (CSK) is a modified sensor histidine kinase found in chloroplasts photosynthetic organelles of plants and algae. CSK regulates the transcription of chloroplast genes in response to changes in photosynthetic electron transport. In this study, the full-length and truncated forms of Arabidopsis CSK proteins were overexpressed and purified in order to characterise their kinase and redox sensing activities. Our results show that CSK contains a modified kinase catalytic domain that binds ATP with high affinity and forms a quinone adduct that may confer redox sensing activity. PMID- 26873740 TI - Maintaining the position of a Bakri balloon after caesarean section for placenta previa using an abdominal traction stitch. PMID- 26873739 TI - Is ERAS in laparoscopic surgery for colorectal cancer changing risk factors for delayed recovery? AB - There is evidence that implementation of enhanced recovery after surgery (ERAS) protocols into colorectal surgery reduces complication rate and improves postoperative recovery. However, most published papers on ERAS outcomes and length of stay in hospital (LOS) include patients undergoing open resections. The aim of this pilot study was to determine the factors affecting recovery and LOS in patients after laparoscopic colorectal surgery for cancer combined with ERAS protocol. One hundred and forty-three consecutive patients undergoing elective laparoscopic resection were prospectively evaluated. They were divided into two subgroups depending on their reaching the targeted length of stay-LOS (75 patients in group 1-<=4 days, 68 patients in group 2->4 days). A univariate and multivariate logistic regression analysis was performed to assess for factors (demographics, perioperative parameters, complications and compliance with the ERAS protocol) independently associated with LOS of 4 days or longer. The median LOS in the entire group was 4 days. The postoperative complication rate was higher (18.7 vs. 36.7 %), and the compliance with ERAS protocol was lower (91.2 vs. 76.7 %) in group 2. There was an association between the pre- and postoperative compliance and the subsequent complications. In uni- and multivariate analysis, the lack of balanced fluid therapy (OR 3.87), lack of early mobilization (OR 20.74), prolonged urinary catheterization (OR 4.58) and use of drainage (OR 2.86) were significantly associated with prolonged LOS. Neither traditional patient risk factors nor the stage of the cancer was predictive of the duration of hospital stay. Instead, compliance with the ERAS protocol seems to influence recovery and LOS when applied to laparoscopic colorectal cancer surgery. PMID- 26873743 TI - Clinical Implication of Proteinase-3-antineutrophil Cytoplasmic Antibody in Patients with Idiopathic Interstitial Pneumonias. AB - PURPOSE: The clinical significance of proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA) positivity is not well established in idiopathic interstitial pneumonia (IIP) patients. We aimed to determine the clinical features of PR3-ANCA positive IIP patients. METHODS: We retrospectively reviewed 377 consecutive IIP patients; of these, 360 patients had PR3-ANCA and myeloperoxidase-antineutrophil cytoplasmic antibody test results available. The clinical features of PR3-ANCA positive IIP patients and control ANCA-negative idiopathic pulmonary fibrosis patients (ANCA-negative IPF) were compared. RESULTS: Sixteen patients (4.4 %) were PR3-ANCA-positive IIP and 94 (26 %) were ANCA-negative IPF. The median age at diagnosis (72 vs. 70 years, P = 0.17) and proportion of males (75 vs. 89 %, P = 0.12) in PR3-ANCA-positive IIP and ANCA-negative IPF patients, respectively, were not significantly different. Radiologically, the HRCT patterns of PR3-ANCA positive IIP patients varied (UIP, n = 3, 18.8 %; possible UIP, n = 3, 18.8 %; NSIP, n = 5, 31.3 %; unclassifiable CT pattern, n = 5, 31.3 %) more than those of ANCA-negative IPF patients (UIP, n = 69, 73.4 %; possible UIP, n = 25, 26.6 %; P < 0.001). No PR3-ANCA-positive IIP patients developed ANCA-associated vasculitis. The 5-year survival rate was 50 % in PR3-ANCA-positive IIP patients and 52 % in ANCA-negative IPF patients with no significant difference (P = 0.96 by log-rank test). CONCLUSIONS: The HRCT patterns of PR3-ANCA-positive IIP patients varied more than those of the IPF patients, but the clinical features of high IIP-onset age and male predominance were similar between the groups. Furthermore, PR3-ANCA positive IIP patients had a poor prognosis similar to that of IPF patients. PMID- 26873741 TI - Macrolides and associated antibiotics based on similar mechanism of action like lincosamides in malaria. AB - Malaria, a parasite vector-borne disease, is one of the biggest health threats in tropical regions, despite the availability of malaria chemoprophylaxis. The emergence and rapid extension of Plasmodium falciparum resistance to various anti malarial drugs has gradually limited the potential malaria therapeutics available to clinicians. In this context, macrolides and associated antibiotics based on similar mechanism of action like lincosamides constitute an interesting alternative in the treatment of malaria. These molecules, whose action spectrum is similar to that of tetracyclines, are typically administered to children and pregnant women. Recent studies have examined the effects of azithromycin and the lincosamide clindamycin, on isolates from different continents. Azithromycin and clindamycin are effective and well tolerated in the treatment of uncomplicated malaria in combination with quinine. This literature review assesses the roles of macrolides and lincosamides in the prophylaxis and treatment of malaria. PMID- 26873742 TI - Characterization of melatonin synthesis in the gastrointestinal tract of rainbow trout (Oncorhynchus mykiss): distribution, relation with serotonin, daily rhythms and photoperiod regulation. AB - Melatonin is synthesized in peripheral locations of vertebrates, including the gastrointestinal tract (GIT). In teleost, information regarding this topic is scarce. Here we studied the presence and synthesis of melatonin at the rainbow trout GIT. Different sections of trout GIT (from esophagus to hindgut) were dissected out and assayed for contents of melatonin, serotonin (5-HT) and its metabolite, 5-hydroxyindole acetic acid, as well as for aanat1, aanat2 and hiomt mRNA abundance. A trout group was pinealectomized to evaluate changes in plasma and gut melatonin content. Finally, the daily profile of melatonin and 5-HT content, and aanat1, aanat2 and hiomt mRNA abundance were analyzed in gut of trout kept under normal lighting, and then under constant darkness. Melatonin was detected in all GIT regions with higher concentrations in the muscular wall than in the mucosa, a similar trend to that of 5-HT. In contrast, transcripts of melatonin synthesis enzymes were more abundant in the mucosa. Pinealectomy did not affect melatonin levels in midgut and hindgut either at day or at night. Additionally, no daily rhythms could be defined for melatonin content in gut tissues but increases during late light phase and at midnight occurred. However, aanat1, aanat2 and hiomt mRNA abundance showed clear daily rhythms with peaks at night. These rhythms remained with a 3-h phase advanced peak in fish exposed to constant darkness. Our results provide clear evidence for a local synthesis of melatonin in trout GIT that might be influenced by the content of 5-HT in the tissue. The process is affected by environmental light cycle and is likely to be under circadian regulation. PMID- 26873744 TI - Methylation on the Circadian Gene BMAL1 Is Associated with the Effects of a Weight Loss Intervention on Serum Lipid Levels. AB - The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment. The study sample enrolled 61 women (body mass index = 28.6 +/- 3.4 kg/m(2); age: 42.2 +/- 11.4 years), who followed a nutritional program based on a Mediterranean dietary pattern. DNA was isolated from whole blood obtained at the beginning and end point. Methylation levels at different CpG sites of BMAL1, CLOCK, and NR1D1 were analyzed by Sequenom's MassArray. The energy-restricted intervention modified the methylation levels of different CpG sites in BMAL1 (CpGs 5, 6, 7, 9, 11, and 18) and NR1D1 (CpGs 1, 10, 17, 18, 19, and 22). Changes in cytosine methylation in the CpG 5 to 9 region of BMAL1 with the intervention positively correlated with the eveningness profile (p = 0.019). The baseline methylation of the CpG 5 to 9 region in BMAL1 positively correlated with energy (p = 0.047) and carbohydrate (p = 0.017) intake and negatively correlated with the effect of the weight loss intervention on total cholesterol (p = 0.032) and low-density lipoprotein cholesterol (p = 0.005). Similar significant and positive correlations were found between changes in methylation levels in the CpG 5 to 9 region of BMAL1 due to the intervention and changes in serum lipids (p < 0.05). This research describes apparently for the first time an association between changes in the methylation of the BMAL1 gene with the intervention and the effects of a weight loss intervention on blood lipids levels. PMID- 26873746 TI - Usefulness of Transcranial Doppler for Detecting Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia. AB - The aim of this study was to assess transcranial Doppler (TCD) as a screening test for pulmonary arteriovenous malformation (PAVM) in patients with hereditary hemorrhagic telangiectasia (HHT). This retrospective study included suspected patients with HHT who were screened for PAVM with a TCD and a chest computed tomography (CT) study. The results of TCD and CT were compared to evaluate the usefulness of TCD for detecting PAVM. A TCD Spencer grade >=3 was defined as positive for a significant right-to-left shunt (RLS). The diameter of the pulmonary arteries feeding the PAVM was measured by calipers from the CT study. In 86 subjects from 74 families with HHT, the sensitivity of TCD for identifying a PAVM at rest was 98% and post-Valsalva was 100%. Specificity was 58% and 35%, respectively, presumably due to pulmonary shunts too small to recognize on CT. Of the patients with HHT who were referred for embolization therapy for their PAVMs, all 20 had TCD grade >=3. In patients who were diagnosed with a PAVM by chest CT, patients with TCD grade >=5 had a significantly larger sum of artery diameters feeding the PAVMs compared to those with grade <=4 (5.0 +/- 3.2 mm vs 2.6 +/- 1.9 mm, p = 0.01). In conclusion, a TCD examination for evaluating RLS is sensitive for identifying PAVM in patients with HHT and is useful in quantitating the degree of RLS flow. The sensitivity of the TCD examination makes it a useful screening test without radiation in HHT subjects to determine which patients need to undergo CT evaluation to identify PAVMs. PMID- 26873745 TI - Nonshaved cranial surgery in black Africans: technical report and a medium-term prospective outcome study. AB - Nonshaved neurosurgery, cranial or spinal, is well reported among Caucasians but hardly among native Africans. The ungroomed scalp hairs of black Africans have unique anthropological characteristics needing special attention for shaveless cranial surgery. A technical report of the execution of this surgical procedure among an indigenous patient population in a sub-Sahara African country is presented, as well as an outcome analysis in a prospective cohort over a 7-year period. A total of 303 patients (211 males, 70 %) fulfilled the criteria for this study. The surgical procedure was primary in 278 (92 %) and redo in 8 %. It was emergency surgery in 153 (51 %). They were trauma craniotomies or decompressive craniectomies in 95 cases (31 %), craniotomies for tumour resections in 86 (28 %), and the surgical dissections for other conditions in 122 (41 %). The duration of surgery ranged from 30 min to 8.5 h, mean 2.5 (SD, 1.6), median 2. In-hospital clinical outcome was good (normal status or moderate deficit on dichotomized Glasgow outcome scale (GOS)) in 273 (90.1 %) cases while surgical site infections occurred in only 10 cases (3.3 %). The type of surgery, redo or primary, did not have any significant association with the in-hospital outcome (p = 0.5), nor with the presence of surgical site infection (SSI) (p = 0.7). The length of follow-up ranged from 2 to 63 months (mean, 7) with no untoward complications reported so far. Medium-term outcome of nonshaved neurosurgery in this indigenous black Africans remains favourable with no attendant significant adverse after-effects. PMID- 26873747 TI - "He Never Did Anything You Typically Think of as Abuse": Experiences With Violence in Controlling and Non-Controlling Relationships in a Non-Agency Sample of Women. AB - Traditionally, any physical aggression within intimate relationships has been labeled "domestic violence," even as researchers and advocates continue to disagree about the nature of that phenomenon vis-a-vis gender and control. As part of a larger mixed-methods study, 22 women from a non-agency, community-based sample who reported experience with relationship violence were interviewed. The existence of patterned coercive and controlling behaviors substantially differentiated experiences with violence, suggesting this dynamic is at least as important to identify as physical violence. Although preliminary, the impact of these findings on intervention and prevention strategies and on the debate surrounding gender symmetry is discussed. PMID- 26873748 TI - An ex vivo liver training model continuously perfused to simulate bleeding for suture skills involved in laparoscopic liver resection: development and validity. AB - BACKGROUND: Suture skills are essential to laparoscopic liver resection. The current suture training models are not ideal enough. The aim of this study is to develop and verify a highly simulated-bleeding continuously perfused training model (CPTM) and to evaluate its training efficacy. METHODS: CPTM was constructed using fresh lamb liver whose portal veins were perfused with red-dyed liquid gelatin. Construct validity of CPTMs was tested in 33 participants with three levels of laparoscopic experience (experts, intermediates, and novices) who were demanded to finish one superficial stitch and one deep stitch for suture hemostasis on CPTMs. The CPTMs were also evaluated by the experts. CPTMs were compared with dry box training models (DBTMs) regarding training efficacy among the novices who were assigned to DBTM and CPTM groups to, respectively, complete a 10-day training on CPTMs or DBTMs. Before and after their assignments, their superficial stitches were assessed by completion time, suture accuracy, and suture knot performance while their deep stitches by completion time and bleeding control. RESULTS: CPTM proved to be construct valid by both superficial and deep stitches. Significant differences were found regarding completion time (763, 271, 174 s), suture accuracy (4.4, 1.8, 0.2 mm), and suturing knot performance (12.1, 21.5, 22.0) for superficial stitches (p < 0.001), as well as regarding completion time (807, 423, 277 s) for deep stitches (p < 0.001). Positive comments were given by all experts. CPTMs helped novices to acquire laparoscopic suture skills. Their training efficacy was significantly better than that of DBTMs (p < 0.05). Learning curves of CPTM group plateaued at the sixth round for superficial stitches and at the seventh round for deep stitches. CONCLUSION: CPTM offers trainees a highly simulated-bleeding means to acquire advanced laparoscopic suture skills. The suture skills learned on CPTMs may improve significantly at the seventh round. PMID- 26873749 TI - The effect of head up tilting on bioreactance cardiac output and stroke volume readings using suprasternal transcutaneous Doppler as a control in healthy young adults. AB - To compare the performance of a bioreactance cardiac output (CO) monitor (NICOM) and transcutaneous Doppler (USCOM) during head up tilting (HUT). Healthy young adult subjects, age 22 +/- 1 years, 7 male and 7 female, were tilted over 3-5 s from supine to 70 degrees HUT, 30 degrees HUT and back to supine. Positions were held for 3 min. Simultaneous readings of NICOM and USCOM were performed 30 s into each new position. Mean blood pressure (MBP), heart rate (HR), CO and stroke volume (SV), and thoracic fluid content (TFC) were recorded. Bland-Altman, percentage changes and analysis of variance for repeated measures were used for statistical analysis. Pre-tilt NICOM CO and SV readings (6.1 +/- 1.0 L/min and 113 +/- 25 ml) were higher than those from USCOM (4.1 +/- 0.6 L/min and 77 +/- 9 ml) (P < 0.001). Bland-Altman limits of agreement for CO were wide with a percentage error of 38 %. HUT increased MBP and HR (P < 0.001). CO and SV readings decreased with HUT. However, the percentage changes in USCOM and NICOM readings did not concur (P < 0.001). Whereas USCOM provided gravitational effect proportional changes in SV readings of 23 +/- 15 % (30 degrees half tilt) and 44 +/- 11 % (70 degrees near full tilt), NICOM changes did not being 28 +/- 10 and 33 +/- 11 %. TFC decreased linearly with HUT. The NICOM does not provide linear changes in SV as predicted by physiology when patients are tilted. Furthermore there is a lack of agreement with USCOM measurements at baseline and during tilting. PMID- 26873751 TI - Androgen actions in mouse wound healing: Minimal in vivo effects of local antiandrogen delivery. AB - The aims of this work were to define the role of androgens in female wound healing and to develop and characterize a novel wound dressing with antiandrogens. Androgens retard wound healing in males, but their role in female wound healing has not been established. To understand androgen receptor (AR) mediated androgen actions in male and female wound healing, we utilized the global AR knockout (ARKO) mouse model, with a mutated AR deleting the second zinc finger to disrupt DNA binding and transcriptional activation. AR inactivation enhanced wound healing rate in males by increasing re-epithelialization and collagen deposition even when wound contraction was eliminated. Cell proliferation and migration in ARKO male fibroblasts was significantly increased compared with wild-type (WT) fibroblasts. However, ARKO females showed a similar healing rate compared to WT females. To exploit local antiandrogen effects in wound healing, while minimizing off-target systemic effects, we developed a novel electrospun polycaprolactone (PCL) scaffold wound dressing material for sustained local antiandrogen delivery. Using the antiandrogen hydroxyl flutamide (HF) at 1, 5, and 10 mg/mL in PCL scaffolds, controlled HF delivery over 21 days significantly enhanced in vitro cell proliferation of human dermal fibroblasts and human keratinocytes. HF-PCL scaffolds also promoted in vivo wound healing in mice compared with open wounds but not to PCL scaffolds. PMID- 26873750 TI - Clinical trial and in-vitro study comparing the efficacy of treating bony lesions with allografts versus synthetic or highly-processed xenogeneic bone grafts. AB - BACKGROUND: Our study aim was to compare allogeneic cancellous bone (ACB) and synthetic or highly-processed xenogeneic bone substitutes (SBS) in the treatment of skeletal defects in orthopedic surgery. METHODS: 232 patients treated for bony lesions with ACB (n = 116) or SBS (n = 116) within a 10-year time period were included in this case-control study. Furthermore, both materials were seeded with human osteoblasts (hOB, n = 10) and analyzed by histology, for viability (AlamarBlue(r)) and protein expression activity (Luminex(r)). RESULTS: The complication rate was 14.2 %, proportion of defects without bony healing 3.6 %; neither outcome parameter differed comparing the intervention groups. Failed consolidation correlated with an increase in complications (p < 0.03). The rate of complications was further highly significant in association with the location of use (p < 0.001), but did not depend on age, ASA risk classification, BMI, smoking behavior or type of insurance. However, those factors did significantly influence the bony healing rate (p < 0.02). Complication and consolidation rates were independent of gender and the filling substances employed within the different locations. Histological examination revealed similar bone structures, whereas cell remnants were apparent only in the allografts. Both materials were biocompatible in-vitro, and seeded with human osteoblasts. The cells remained vital over the 3-week culture period and produced microscopically typical bone matrix. We observed initially increased expression of osteocalcin, osteopontin, and osteoprotegerin as well as leptin and adiponectin secretion declining after 1 week, especially in the ACB group. CONCLUSION: Although both investigated materials appeared to be similarly suitable for the treatment of skeletal lesions in-vivo and in-vitro, outcome was decisively influenced by other factors such as the site of use or epidemiological parameters. PMID- 26873752 TI - miR-19a, -19b, and -26b Mediate CTGF Expression and Pulmonary Fibroblast Differentiation. AB - Although microRNA (miRNA) dysregulation with intracellular signaling cascade disruption has been demonstrated in the pathophysiology of pulmonary fibrosis, the relationship between miRNAs and intracellular signaling cascades in pulmonary fibrosis remains unclear. Using the human embryonic lung fibroblast cell line WI 38, we observed endothelin-1 (ET-1)- and thrombin-induced expression of the differentiation markers alpha-smooth muscle actin (alpha-SMA) and vimentin along with increased connective tissue growth factor (CTGF) protein expression. Decreased CTGF protein expression by CTGF siRNA significantly blocked ET-1- and thrombin-induced alpha-SMA and vimentin expression in WI-38 cells. Activation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase ERK, c-Jun N-terminal kinase (JNK), and p38 contributed to ET-1- and thrombin-induced CTGF, alpha-SMA, and vimentin expression in WI-38 cells. TargetScan Human, miRanda, and PicTar prediction algorithms were used to predict miRNAs with binding sites in the 3' untranslated region (UTR) of CTGF mRNA. miR 19a, -19b, and -26b were candidate miRNAs of CTGF. Direct binding of the candidate miRNAs to the 3'-UTR of CTGF mRNA was verified through luciferase assay by using SV40-promoter-IRES-driven luciferase containing the 3'-UTR of CTGF mRNA as a reporter plasmid. ET-1 and thrombin reduced candidate miRNA levels. Candidate miRNA overexpression significantly suppressed ET-1- and thrombin induced CTGF expression and reduced alpha-SMA and vimentin expression in the WI 38 cells. Furthermore, candidate miRNA levels were decreased in the lung tissues of mice with bleomycin-induced pulmonary fibrosis, and intratracheal application of miR-19a, -19b, and 26b reduced the pulmonary fibrotic severity induced by bleomycin. This study is the first to demonstrate crosstalk between MAPK activation and reduction in miR-19a, -19b, and -26b expression leading to lung fibroblast differentiation. J. Cell. Physiol. 231: 2236-2248, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26873753 TI - The Tao survivorship of schistosomes: implications for schistosomiasis control. AB - Schistosomiasis, caused by blood flukes of the genus Schistosoma, is a major public health problem which contributes substantially to the economic and financial burdens of many nations in the developing world. An array of survival strategies, such as the unique structure of the tegument which acts as a major host-parasite interface, immune modulation mechanisms, gene regulation, and apoptosis and self-renewal have been adopted by schistosome parasites over the course of long-term evolution with their mammalian definitive hosts. Recent generation of complete schistosome genomes together with numerous biological, immunological, high-throughput "-omics" and gene function studies have revealed the Tao or strategies that schistosomes employ not only to promote long-term survival, but also to ensure effective life cycle transmission. New scenarios for the future control of this important neglected tropical disease will present themselves as our understanding of these Tao increases. PMID- 26873755 TI - The Bedside Nurse: The Foundation of Multimodal Neuromonitoring. AB - Although technology over the past several decades has enabled improved neuroimaging and advanced noninvasive and invasive neuromonitoring, the role of the bedside nurse conducing ongoing neurologic examination is still a foundational element of neuromonitoring. Ongoing neurologic monitoring by the bedside nurse in the neuroscience intensive care unit is variable and guided by little evidence or data. When neurologic monitoring through clinical examination is possible, data obtained from multimodal monitoring should be interpreted in the context of the neurologic examination. The bedside nurse plays a crucial role in conducting ongoing neurologic examinations. PMID- 26873756 TI - Blood Pressure Management Controversies in Neurocritical Care. AB - Blood pressure (BP) management is essential in neurocritical care settings to ensure adequate cerebral perfusion and prevent secondary brain injury. Despite consensus on the importance of BP monitoring, significant practice variations persist regarding optimal methods for monitoring and treatment of BP values among patients with neurologic injuries. This article provides a summary of research investigating various approaches for BP management in neurocritical care. Evidence-based recommendations, areas for future research, and current technological advancements for BP management are discussed. PMID- 26873757 TI - Delirium in the Neuro Intensive Care Unit. AB - This article reviews current literature regarding the neuro intensive care unit (ICU) and the ICU setting in general regarding delirium, pain, agitation, and evidence-based guidelines and assessment tools. Delirium in the ICU affects as many as 50% to 80% of patients. Delirium is associated with increased burden of illness, higher mortality, and increased suffering. Evidence-based guidelines recommend using validated and reliable assessment tools. We reviewed current national clinical guidelines, validated tools for assessing pain, agitation/sedation, and delirium. We also reviewed a delirium risk assessment/prediction tool. PMID- 26873754 TI - Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex. AB - Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field. PMID- 26873758 TI - Neuroradiology of the Brain. AB - A variety of imaging modalities are currently used to evaluate the brain. Prior to the 1970s, neurologic imaging involved radiographs, invasive procedures for spinal and carotid artery air and contrast injection, and painful patient manipulation. The brain was considered inaccessible to imaging and referred to as "the dark continent." Since then, advances in neuroradiology have moved the brain from being a dark continent to evaluation techniques that illuminate brain contents and pathology. These advances enable quick acquisition of images for prompt diagnosis and treatment. This article reviews anatomy, diagnostic principles, and clinical application of brain imaging beyond plain radiographs. PMID- 26873759 TI - Management of Refractory Intracranial Pressure. AB - Patients with refractory intracranial pressure represent a challenge to the multidisciplinary critical care team. Myriad diagnoses: traumatic brain injury, subarachnoid hemorrhage, intracranial hemorrhage, and ischemic stroke, are among the causes commonly seen in patients with elevated intracranial pressure. Clinicians tasked with caring for these patients must be aware of available interventions and management strategies to improve outcomes. Nurses as the bedside clinician most frequently assessing these patients are ideally situated to detect changes and act efficiently to lower refractory intracranial pressure. PMID- 26873760 TI - Invasive Neuromonitoring. AB - Advances in technology have resulted in a plethora of invasive neuromonitoring options for practitioners to manage while caring for the complex needs of the critical care patient. Although many types of invasive neuromonitoring are available to the practitioner, intraparenchymal monitors and external ventricular devices are used most frequently in the clinical setting and are the focus of this article. In addition, multimodality monitoring has been noted to confer a survival benefit in patients with this complex type of invasive neuromonitoring and is discussed as well. PMID- 26873761 TI - Principles of Neuro-anesthesia in Neurosurgery for Intensive Care Unit Nurses. AB - As neurosurgical interventions and procedures are advancing, so is the specialty of neuro-anesthesia. The neurosurgeon and the neuro-anesthetist are focused on providing each patient with the best possible outcome. Throughout the surgery, the main priorities of the neuro-anesthetist are patient safety, patient well being, surgical field exposure, and patient positioning. Potential postoperative complications include nausea and vomiting. Postoperative visual loss is a complication of neurosurgery, most specifically spine surgery, whose origins are unknown. Postoperative considerations for the intensive care unit nurse should include receiving a thorough clinical handoff from the anesthesia provider to ensure care continuity and patient safety. PMID- 26873762 TI - Optic Nerve Sheath Diameter Ultrasound and the Diagnosis of Increased Intracranial Pressure. AB - Ultrasound has been used for almost 30 years in a wide variety of clinical applications and environments. From the austerity of battlefields to the labor and delivery ward, ultrasound has the ability to give clinicians real-time, noninvasive diagnostic imaging. Ultrasound by emergency physicians (and all nonradiologists) has become more prevalent and has been used for examinations such as the transcranial Doppler to evaluate for stroke, cardiac function, FAST and EFAST examinations for trauma, and now increased intracranial pressure (ICP) via Optic Nerve Sheath Diameter Ultrasound (ONSD). The ONSD is a valid and reliable indicator of ICP. PMID- 26873763 TI - The Use of Automated Pupillometry in Critical Care. AB - The neurologic examination (neuroexamination) is one of the most powerful tools available to nurses and physicians caring for patients with neurologic or neurosurgical illness. Assessing cranial nerve function is one of the most vital components of the neuroexamination. The pupillary light reflex helps to evaluate the status of the second and third cranial nerves and is one of the most well known elements of the cranial nerve examination. Automated pupillometers have been developed that provide objective measures of size of the pupil and the responsiveness of the pupil to light (neuropupillary index). PMID- 26873764 TI - Cerebral Microdialysis. AB - A variety of neuromonitoring techniques are available to aid in the care of neurocritically ill patients. However, traditional monitors lack the ability to measure brain biochemistry and may provide inadequate warning of potentially reversible deleterious conditions. Cerebral microdialysis (CMD) is a safe, novel method of monitoring regional brain biochemistry. Analysis of CMD analytes as part of a multimodal approach may help inform clinical decision making, guide medical treatments, and aid in prognostication of patient outcome. Its use is most frequently documented in traumatic brain injury and subarachnoid hemorrhage. Incorporating CMD into clinical practice is a multidisciplinary effort. PMID- 26873765 TI - Targeted Temperature Modulation in the Neuroscience Patient. AB - There are many approaches to and opportunities for implementing temperature modulation in critically ill patients, but barriers also exist. Conceptually, the process of cooling is rather straightforward; however, targeted temperature management is anything but simplistic. The need for a collaborative approach (physicians champions, nursing support, respiratory therapists, pharmacists, laboratory personnel, and supply chain representatives) to address definitions of normothermia and fever, patient inclusion/exclusion criteria for therapy based on underlying neurorelated pathologies, determination of methods of induction/maintenance, monitoring required, education planning, and strategies to minimize potential complications are warranted. PMID- 26873766 TI - Neuromonitoring in the Intensive Care Unit. PMID- 26873767 TI - Multiple mini-interviews as a predictor of academic achievements during the first 2 years of medical school. AB - BACKGROUND: Recently, conventional interviews have been replaced with the multiple mini-interviews (MMI) for medical student selection in Korea. We first introduced the MMI as a new admissions tool in Korea. The aim of this study is to determine whether the MMI accurately predicts academic achievement on both written and performance-based examinations during the first 2 years of medical school. METHODS: The original scores of each station were standardized to T scores in the candidates group. Three cohorts of students were included depending upon the year they entered medical school. Pearson's correlations were calculated to estimate the correlations between MMI scores and academic achievements. Additional correlated factors were run through multiple stepwise linear regression analysis to estimate predictive validity. RESULTS: There were no differences between T-scores or grade point averages (GPA) among the cohorts. The correlation coefficients between total MMI scores and academic achievement in Year 1 and the Year 2 performance-based examinations ranged from 0.17 to 0.43. Station 1 significantly predicted academic achievement over the second year. Station 3 significantly predicted only performance-based examination performance over the second year. CONCLUSION: MMI is a useful tool to assist with medical student selection. In particular, critical thinking, professionalism, and presentation and communication skills may be meaningful topics for predicting academic achievements, especially in performance-based subjects. PMID- 26873768 TI - Kocher-Debre-Semelaigne's syndrome: A case report. PMID- 26873769 TI - Founding an undergraduate society: a student-led initiative to improve dermatology education. PMID- 26873770 TI - Hereditary gingival fibromatosis with extreme ridge thickness and insufficient interarch distance: A clinical report of surgical and prosthetic management. AB - Hereditary gingival fibromatosis is a rare genetic disorder resulting in gingival overgrowth that can be found in both dental arches. As a result of the gingival overgrowth and associated dental displacement, affected patients occasionally present with increased occlusal vertical dimension and/or inadequate lip closure. Depending on the disorder's severity, these patients can be challenging to treat. This clinical report describes a comprehensive surgical and prosthetic approach to the rehabilitation of a middle-aged patient with severe manifestations of hereditary gingival fibromatosis and severe generalized chronic periodontitis. PMID- 26873771 TI - Cytotoxic evaluation of hydroxyapatite-filled and silica/hydroxyapatite-filled acrylate-based restorative composite resins: An in vitro study. AB - STATEMENT OF PROBLEM: Although the physical and mechanical properties of hydroxyapatite-filled dental restorative composite resins have been examined, the biocompatibility of these materials has not been studied in detail. PURPOSE: The purpose of this in vitro study was to analyze the toxicity of acrylate-based restorative composite resins filled with hydroxyapatite and a silica/hydroxyapatite combination. MATERIAL AND METHODS: Five different restorative materials based on bisphenol A-glycidyl methacrylate (bis-GMA) and tri-ethylene glycol dimethacrylate (TEGDMA) were developed: unfilled (H0), hydroxyapatite-filled (H30, H50), and silica/hydroxyapatite-filled (SH30, SH50) composite resins. These were tested for in vitro cytotoxicity by using human bone marrow mesenchymal stromal cells. Surface morphology, elemental composition, and functional groups were determined by scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), and Fourier-transformed infrared spectroscopy (FTIR). The spectra normalization, baseline corrections, and peak integration were carried out by OPUS v4.0 software. RESULTS: Both in vitro cytotoxicity results and SEM analysis indicated that the composite resins developed were nontoxic and supported cell adherence. Elemental analysis with EDX revealed the presence of carbon, oxygen, calcium, silicon, and gold, while the presence of methacrylate, hydroxyl, and methylene functional groups was confirmed through FTIR analysis. CONCLUSIONS: The characterization and compatibility studies showed that these hydroxyapatite-filled and silica/hydroxyapatite-filled bis-GMA/TEGDMA-based restorative composite resins are nontoxic to human bone marrow mesenchymal stromal cells and show a favorable biologic response, making them potential biomaterials. PMID- 26873772 TI - Vow to impose contract means further action is "inevitable," says junior doctors' leader. PMID- 26873773 TI - A dermatologist at heart: the Osler legacy at Johns Hopkins. PMID- 26873774 TI - Spontaneously occurring fundus findings observed using confocal scanning laser ophthalmoscopy in wild type Sprague Dawley rats. AB - PURPOSE: Non-invasive in vivo imaging is an increasingly used component of pre clinical research. However, to reliably interpret data, it may be necessary to identify and document pre-existent findings prior to initiating long-term or intensive protocols, particularly where toxicity or efficacy is under investigation. Here we report here spontaneously occurring findings from the Sprague Dawley (SD) rat eye using multi-modal confocal scanning laser ophthalmoscopy (cSLO). METHODS: As part of ongoing studies, with the goal of excluding animals with abnormalities from further investigation, a total of 165 wild type SD rats (312 eyes) were assessed using cSLO imaging at baseline prior to initiating experiments to detect, describe, and determine the prevalence of spontaneous fundus findings. RESULTS: Using fundus autofluorescence (FAF) as the primary screening modality, over 30% of analyzed eyes possessed some fundus finding that differed from the normal composite reference image. Unexpectedly, 100% of eyes demonstrated a diffuse hyperfluorescent region in the posterior pole that was ultimately considered normal, and formed part of the reference. Evaluated by three independent reviewers, five groups of FAF abnormalities were defined, based primarily on shape and size of the lesion. Of these, the most extensive lesions were further analyzed using infrared reflectance (IR) and red free (RF) imaging. White light and autofluorescent microscopy of excised tissue confirmed that the extensive lesions were derived from abnormalities in both the isolated retina and posterior eyecups. CONCLUSIONS: Given the newly described hyperfluorescent glow that appears in all eyes, and the high basal rate of spontaneous lesions in the outbred SD rat, we suggest that investigators be aware of the variants of normal, and that baseline in vivo screening be considered prior to initiating intensive or expensive investigation. PMID- 26873775 TI - Promoting the 3Rs to enhance the OECD fish toxicity testing framework. AB - Fish toxicity testing has been conducted since the 1860's in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework. PMID- 26873776 TI - Perceived magnitude of visual displays: Area, numerosity, and mean size. AB - Previous studies have shown that the visual system is able to estimate properties such as area, numerosity, and mean size efficiently and accurately. In the current study, we investigated whether our percepts of each of them could be based on ratios of the other two of these three properties. In each trial, observers viewed a display containing various quantities of filled circles and judged whether the magnitude of a property of the display, such as summed area, numerosity, or average size of the circles, was greater or less than a corresponding probe display. We found that mean size judgments were more accurate and precise compared to the other judgments. We then predicted observers' performances for each task using the measured performance for the other judgments. The results showed that the other properties predicted perceived summed area, but not perceived mean size and numerosity. Together, our results suggest that the visual system does not use ratios to compute mean size and numerosity. PMID- 26873777 TI - Perceptual learning of basic visual features remains task specific with Training Plus-Exposure (TPE) training. AB - Visual perceptual learning is known to be specific to the trained retinal location, feature, and task. However, location and feature specificity can be eliminated by double-training or TPE training protocols, in which observers receive additional exposure to the transfer location or feature dimension via an irrelevant task besides the primary learning task Here we tested whether these new training protocols could even make learning transfer across different tasks involving discrimination of basic visual features (e.g., orientation and contrast). Observers practiced a near-threshold orientation (or contrast) discrimination task. Following a TPE training protocol, they also received exposure to the transfer task via performing suprathreshold contrast (or orientation) discrimination in alternating blocks of trials in the same sessions. The results showed no evidence for significant learning transfer to the untrained near-threshold contrast (or orientation) discrimination task after discounting the pretest effects and the suprathreshold practice effects. These results thus do not support a hypothetical task-independent component in perceptual learning of basic visual features. They also set the boundary of the new training protocols in their capability to enable learning transfer. PMID- 26873778 TI - Exogenously triggered perceptual switches in multistable structure-from-motion occur in the absence of visual awareness. AB - Here, we characterize the duration of exogenously triggered perceptual switches in an ambiguously rotating structure-from-motion display and demonstrate their independence on visual awareness. To this end, we triggered a perceptual reversal by inverting the on-screen motion and systematically varied the posttrigger presentation duration, while collecting observers' reports about the initial and final directions of illusory rotation. We demonstrate that for the structure-from motion display, perceptual transitions are extremely brief (<= 20 ms) and can be considered instantaneous from an experimental perspective. We also report that although very brief posttrigger intervals (10-20 ms) reliably initiate a perceptual reversal, observers become aware of perceptual switches only if the posttrigger presentation continues for at least 80 ms. Additional experiments demonstrated that an observed lack of visual awareness for brief posttrigger presentation intervals cannot be attributed to either a systematic delay of visual awareness or to backward masking. Our results show that exogenously triggered perceptual reversal can occur in the absence of visual awareness, extending earlier work on spontaneous reversals that indicated that neither awareness nor attention may be required for multistable perception. Methodologically, the brevity and the short latency of induced perceptual reversals make them particularly suitable for finely timed experiments, such as magneto/electroencephalography studies. PMID- 26873779 TI - Characterization of the life cycle of the tick Haemaphysalis tibetensis under field conditions in Qinghai-Tibet plateau. AB - The tick Haemaphysalis tibetensis Hoogstraal is found uniquely in the Qinghai Tibet plateau of Tibet and Gansu of China. Not much is known of this tick. Therefore, in this study we investigated the life cycle of H. tibetensis under field conditions from March 2014 to March 2015 in Damxung County, north Lhasa City in Tibet (Autonomous Region in China). The results of the study demonstrated that the tick H. tibetensis requires an average of 177.8 days (range 129-202 days) to complete a life cycle, with rabbits supplied as hosts in the field plot. Under natural lighting and climate conditions, the feeding period of females was an average of 7.7 days, and the pre-oviposition period was 9.4 days, followed by 28.2 days for oviposition. The premolting period of nymphs lasted 52.7 days, which was the longest life cycle phase. The average weight ratio of engorged to unfed females was 58.2. Additionally, there was a highly positive correlation between the weight of engorged and the number of the eggs that were laid (r = 0.83, P < 0.05). The reproductive efficiency index and reproductive fitness index in females were 5.1 and 4.7, respectively. PMID- 26873780 TI - A method and software framework for enriching private biomedical sources with data from public online repositories. AB - Modern biomedical research relies on the semantic integration of heterogeneous data sources to find data correlations. Researchers access multiple datasets of disparate origin, and identify elements-e.g. genes, compounds, pathways-that lead to interesting correlations. Normally, they must refer to additional public databases in order to enrich the information about the identified entities-e.g. scientific literature, published clinical trial results, etc. While semantic integration techniques have traditionally focused on providing homogeneous access to private datasets-thus helping automate the first part of the research, and there exist different solutions for browsing public data, there is still a need for tools that facilitate merging public repositories with private datasets. This paper presents a framework that automatically locates public data of interest to the researcher and semantically integrates it with existing private datasets. The framework has been designed as an extension of traditional data integration systems, and has been validated with an existing data integration platform from a European research project by integrating a private biological dataset with data from the National Center for Biotechnology Information (NCBI). PMID- 26873781 TI - Is the crowd better as an assistant or a replacement in ontology engineering? An exploration through the lens of the Gene Ontology. AB - Biomedical ontologies contain errors. Crowdsourcing, defined as taking a job traditionally performed by a designated agent and outsourcing it to an undefined large group of people, provides scalable access to humans. Therefore, the crowd has the potential to overcome the limited accuracy and scalability found in current ontology quality assurance approaches. Crowd-based methods have identified errors in SNOMED CT, a large, clinical ontology, with an accuracy similar to that of experts, suggesting that crowdsourcing is indeed a feasible approach for identifying ontology errors. This work uses that same crowd-based methodology, as well as a panel of experts, to verify a subset of the Gene Ontology (200 relationships). Experts identified 16 errors, generally in relationships referencing acids and metals. The crowd performed poorly in identifying those errors, with an area under the receiver operating characteristic curve ranging from 0.44 to 0.73, depending on the methods configuration. However, when the crowd verified what experts considered to be easy relationships with useful definitions, they performed reasonably well. Notably, there are significantly fewer Google search results for Gene Ontology concepts than SNOMED CT concepts. This disparity may account for the difference in performance - fewer search results indicate a more difficult task for the worker. The number of Internet search results could serve as a method to assess which tasks are appropriate for the crowd. These results suggest that the crowd fits better as an expert assistant, helping experts with their verification by completing the easy tasks and allowing experts to focus on the difficult tasks, rather than an expert replacement. PMID- 26873782 TI - Single-molecule force spectroscopy on polyproteins and receptor-ligand complexes: The current toolbox. AB - Single-molecule force spectroscopy sheds light onto the free energy landscapes governing protein folding and molecular recognition. Since only a single molecule or single molecular complex is probed at any given point in time, the technique is capable of identifying low-probability conformations within a large ensemble of possibilities. It furthermore allows choosing certain unbinding pathways through careful selection of the points at which the force acts on the protein or molecular complex. This review focuses on recent innovations in construct design, site-specific bioconjugation, measurement techniques, instrumental advances, and data analysis methods for improving workflow, throughput, and data yield of AFM based single-molecule force spectroscopy experiments. Current trends that we highlight include customized fingerprint domains, peptide tags for site-specific covalent surface attachment, and polyproteins that are formed through mechanostable receptor-ligand interactions. Recent methods to improve measurement stability, signal-to-noise ratio, and force precision are presented, and theoretical considerations, analysis methods, and algorithms for analyzing large numbers of force-extension curves are further discussed. The various innovations identified here will serve as a starting point to researchers in the field looking for opportunities to push the limits of the technique further. PMID- 26873783 TI - 3DBIONOTES: A unified, enriched and interactive view of macromolecular information. AB - With the advent of high throughput techniques like Next Generation Sequencing, the amount of biological information for genes and proteins is growing faster than ever. Structural information is also rapidly growing, especially in the cryo Electron Microscopy area. However, in many cases, the proteomic and genomic data are spread in multiple databases and with no simple connection to structural information. In this work we present a new web platform that integrates EMDB/PDB structures and UniProt sequences with different sources of protein annotations. The application provides an interactive interface linking sequence and structure, including EM maps, presenting the different sources of information at sequence and structural level. The web application is available at http://3dbionotes.cnb.csic.es. PMID- 26873784 TI - The Electron Microscopy eXchange (EMX) initiative. AB - Three-dimensional electron microscopy (3DEM) of ice-embedded samples allows the structural analysis of large biological macromolecules close to their native state. Different techniques have been developed during the last forty years to process cryo-electron microscopy (cryo-EM) data. Not surprisingly, success in analysis and interpretation is highly correlated with the continuous development of image processing packages. The field has matured to the point where further progress in data and methods sharing depends on an agreement between the packages on how to describe common image processing tasks. Such standardization will facilitate the use of software as well as seamless collaboration, allowing the sharing of rich information between different platforms. Our aim here is to describe the Electron Microscopy eXchange (EMX) initiative, launched at the 2012 Instruct Image Processing Center Developer Workshop, with the intention of developing a first set of standard conventions for the interchange of information for single-particle analysis (EMX version 1.0). These conventions cover the specification of the metadata for micrograph and particle images, including contrast transfer function (CTF) parameters and particle orientations. EMX v1.0 has already been implemented in the Bsoft, EMAN, Xmipp and Scipion image processing packages. It has been and will be used in the CTF and EMDataBank Validation Challenges respectively. It is also being used in EMPIAR, the Electron Microscopy Pilot Image Archive, which stores raw image data related to the 3DEM reconstructions in EMDB. PMID- 26873785 TI - Assessment of ionization chamber correction factors in photon beams using a time saving strategy with PENELOPE code. AB - The purpose of this study was to investigate Monte Carlo-based perturbation and beam quality correction factors for ionization chambers in photon beams using a saving time strategy with PENELOPE code. Simulations for calculating absorbed doses to water using full spectra of photon beams impinging the whole water phantom and those using a phase-space file previously stored around the point of interest were performed and compared. The widely used NE2571 ionization chamber was modeled with PENELOPE using data from the literature in order to calculate absorbed doses to the air cavity of the chamber. Absorbed doses to water at reference depth were also calculated for providing the perturbation and beam quality correction factors for that chamber in high energy photon beams. Results obtained in this study show that simulations with phase-space files appropriately stored can be up to ten times shorter than using a full spectrum of photon beams in the input-file. Values of kQ and its components for the NE2571 ionization chamber showed good agreement with published values in the literature and are provided with typical statistical uncertainties of 0.2%. Comparisons to kQ values published in current dosimetry protocols such as the AAPM TG-51 and IAEA TRS-398 showed maximum percentage differences of 0.1% and 0.6% respectively. The proposed strategy presented a significant efficiency gain and can be applied for a variety of ionization chambers and clinical photon beams. PMID- 26873786 TI - X-ray fiber diffraction analysis shows dynamic changes in axial tubulin repeats in native microtubules depending on paclitaxel content, temperature and GTP hydrolysis. AB - Microtubules are key components of the cytoskeleton in eukaryotic cells. The dynamics between assembled microtubules and free tubulin dimers in the cytoplasm is closely related to the active shape changes of microtubule networks. One of the most fundamental questions is the association of microtubule dynamics with the molecular conformation of tubulin within microtubules. To address this issue, we applied a new technique for the rapid shear-flow alignment of biological filaments, enabling us to acquire the structural periodicity data of microtubules by X-ray fiber diffraction under various physiological conditions. We classified microtubules into three main groups on the basis of distinct axial tubulin periodicities and mean microtubule diameters that varied depending on GTP hydrolysis and the content of paclitaxel, a microtubule stabilizer. Paclitaxel induced rapid changes in tubulin axial repeats in a cooperative manner. This is the first demonstration of dynamic changes of axial tubulin repeats within native microtubules without fixation. We also found extraordinary features of negative thermal expansion of axial tubulin repeats in both paclitaxel-stabilized and GMPCPP-containing microtubules. Our results suggest that even in assembled microtubules, both GTP- and GDP-tubulin dimers can undergo dynamic conversion between at least two different states: short and long configurations. PMID- 26873787 TI - Quality control of antibodies for assay development. AB - Antibodies are used as powerful tools in basic research, for example, in biomarker identification, and in various forms for diagnostics, for example, identification of allergies or autoimmune diseases. Due to their robustness and ease of handling, immunoassays are favourite methods for investigation of various biological or medical questions. Nevertheless in many cases, additional analyses such as mass spectrometry are used to validate or confirm the results of immunoassays. To minimize the workload and to increase confidence in immunoassays, there are urgent needs for antibodies which are both highly specific and well validated. Unfortunately many commercially available antibodies are neither well characterized nor fully tested for cross-reactivities. Adequate quality control and validation of an antibody is time-consuming and can be frustrating. Such validation needs to be performed for every assay/application. However, where an antibody validation is successful, a highly specific and stable reagent will be on hand. This article describes the validation processes of antibodies, including some often neglected factors, as well as unspecific binding to other sample compounds in a multiparameter diagnostic assay. The validation consists of different immunological methods, with important assay controls, and is performed in relation to the development of a diagnostic test. PMID- 26873790 TI - Impact of stereotactic radiotherapy on kidney function in primary renal cell carcinoma: Establishing a dose-response relationship. AB - BACKGROUND AND PURPOSE: To evaluate renal dysfunction after stereotactic ablative body radiotherapy (SABR) for inoperable primary renal cell carcinoma (RCC) using nuclear medicine assessments. MATERIALS AND METHODS: In a prospective clinical trial, patients received single fraction renal SABR (26 Gy) for tumours <5 cm, or fractionated SABR (3 * 14 Gy) for tumours ?5 cm. Global and regional glomerular filtration rate (GFR) was calculated through (51)Cr-EDTA and (99m)Tc-DMSA SPECT/CT, respectively, at baseline and post-treatment (14, 90 days and at 1 year). Regional loss in function was correlated to the absolute and biologically effective doses (BED) delivered. RESULTS: In 21 patients the mean (range) tumour size was 48 mm (21-75 mm). The mean +/- SD GFR at baseline was 52 +/- 24 ml/min. Net change in mean GFR was +0.6 +/- 11.3, +3.2 +/- 14.5 and -8.7 +/- 13.4 ml/min (p=0.03) at 2 weeks, 3 months and 1 year, respectively. For every 10 Gy of physical dose delivered, an exponential decline in affected kidney GFR was observed at 39% for 26 Gy/1 fraction and 25% for 42 Gy/3 fractions. When normalised to BED3Gy, the dose-response relationship for each treatment prescription was similar with a plateau beyond 100 Gy. The R50% conformity index correlated with GFR loss (p=0.04). No patient required dialysis. CONCLUSIONS: SABR results in clinically acceptable and dose-dependent renal dysfunction at 1 year. Sparing functional kidney from high-dose regions (>50% isodoses) may help reduce risk of functional loss. PMID- 26873791 TI - On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy. AB - PURPOSE: To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. METHODS AND MATERIALS: The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). RESULTS: Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. CONCLUSIONS: The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study. PMID- 26873788 TI - Harnessing the integrated stress response for the treatment of multiple sclerosis. AB - Multiple sclerosis is a chronic demyelinating autoimmune disease of the CNS with no known cure. Although 12 immunomodulatory therapies exist, they have only modest effects on disease progression. The field has therefore focused on the development of alternative treatment strategies, such as enhancement of remyelination and CNS repair. Progress has been made on a third, complementary treatment approach that aims to protect oligodendrocytes-and the myelin they generate and maintain-from inflammation-mediated death by enhancing the integrated stress response. Studies in cells and in mouse models of multiple sclerosis have shown that this innate protective pathway, which maintains proteostasis, can be harnessed effectively to protect oligodendrocytes and myelin during inflammation. With one drug already in clinical development for patients with multiple sclerosis, and several potential therapies under investigation, modulation of the integrated stress response might become an important component of strategies to halt the progression of the disease. PMID- 26873789 TI - Lean-seafood intake decreases urinary markers of mitochondrial lipid and energy metabolism in healthy subjects: Metabolomics results from a randomized crossover intervention study. AB - SCOPE: Proteins constitute an important part of the human diet, but understanding of the effects of different dietary protein sources on human metabolism is sparse. We aimed to elucidate diet-induced metabolic changes through untargeted urinary metabolomics after four weeks of intervention with lean-seafood or nonseafood diets. It is shown that lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects. METHODS: In a randomized controlled trial with crossover design, 20 healthy subjects consumed two balanced diets that varied in main protein sources for 4 weeks. Morning spot urine samples were collected before and after each intervention period. Untargeted metabolomics based on (1) H NMR spectroscopy and LC-MS analyses were applied to characterize the urinary metabolic response to the interventions. RESULTS: The lean-seafood diet period reduced the urinary level of l-carnitine, 2,6-dimethylheptanoylcarnitine, and N-methyl-2-pyridone-5-carboxamide, relative to the nonseafood period. The dietary analysis revealed that the higher urinary level of trimethylamine-N-oxide after the lean-seafood diet period and guanidinoacetate and 3-methylhistidine after the nonseafood diet period was related to the endogenous content of these compounds in the diets. CONCLUSIONS: Our data reveal that 4 weeks of lean-seafood intake reduces urinary excretion of metabolites involved in mitochondrial lipid and energy metabolism possibly facilitating a higher lipid catabolism in healthy subjects after the lean-seafood intake. PMID- 26873792 TI - Association between radiation dose to the heart and myocardial fatty acid metabolic impairment due to chemoradiation-therapy: Prospective study using I-123 BMIPP SPECT/CT. AB - PURPOSE: To investigate long term changes in myocardial fatty acid metabolic impairment caused by chemoradiation-therapy (CRT). MATERIALS AND METHODS: We investigated 12 esophageal cancer patients who underwent SPECT/CT using I-123 labeled fatty acid analog (BMIPP) at pre-CRT, pre-boost irradiation, 3-month post CRT, and 1-year post-CRT. The myocardial uptake was measured using the defect score and the total percentage of uptake (%uptake), which were defined as the sum of the visual scores and that of %uptake in each of 17 segments in the left ventricle (LV), respectively. The correlations between radiation dose to the heart (mean dose, V20, V40, and V60 of the LV and the whole heart (WH)) and the change of myocardial BMIPP uptake from pre-CRT (Deltamyocardial BMIPP uptake) were assessed. RESULTS: At pre-boost, Deltamyocardial BMIPP uptake was significantly correlated with LV-V40 and WH-V60. At 3-month post-CRT, Deltamyocardial BMIPP uptake was significantly correlated with LV-V40, WH-V40, and WH-V60. However, there were no statistically significant correlations at 1 year post-CRT. Neither mean dose nor V20 of the LV/WH was significantly correlated with Deltamyocardial BMIPP uptake at any time. CONCLUSIONS: In the long term after CRT, myocardial metabolism might be affected by factors other than the radiation dose to the heart. PMID- 26873795 TI - Is low-molecular weight iron dextran really the most risky iron?--Unconvincing data from an unconvincing study. PMID- 26873796 TI - Of Grief and Well-being: Competing Conceptions of Restorative Ritualization. AB - Informants' accounts of what they did with ashes they had chosen to remove from UK crematoria described disposal and memorialization strategies that have implications for anthropological understanding of issues of well-being, and the generation of new ritual practices. Here we aim to explore informants' conceptions of how well-being might be restored after a bereavement and how these were being put into practice. Data were gathered as part of an Economic and Social Research Council (ESRC) funded project, which used qualitative interviewing and focus groups among professionals involved with independent ash disposal; and individuals who had removed the ashes of relative or friend from a crematorium. Barking and Dagenham, Nottingham, Sunderland and Glasgow were our field sites. Analysis involved recognizing these data as 'motivated narratives' (Bury 2001 ) that, for example, extended informants' relationships with the dead, as well as reflecting tensions between professionals' imperatives to complete work with a client and their commitment to offering individual choice and support during their ongoing relationship with the dead. Such findings highlight the contested nature of contemporary conceptions of restorative ritual, with tensions existing between the meta-narratives of individual choice and professional expertise; between different individuals' 'choices'; and between the event of a death ritual and the process of ritualization. These findings contribute a nuanced account of the diversity of discursive practices through which the individuals, both 'lay' and professional, involved in a particular death, might understand how well-being can be restored. PMID- 26873794 TI - Core muscle recruitment pattern during voluntary heel raises is different between patients with patellofemoral pain and healthy individuals. AB - BACKGROUND: Recent studies suggest that the inconsistent outcomes of patellofemoral pain (PFP) treatment may result from the unclear understanding of changes in the structures remote from the knee joint. Due to the crucial influence of core stability on the knee function, this study aimed to evaluate the recruitment pattern of core muscles in individuals with and without PFP. METHODS: Sixty women aged 18 to 40years, including 30 subjects diagnosed with PFP and 30 healthy controls rose on to their toes as quickly and strongly as possible in response to a sound alarm in standing position. Electromyographic onsets of the transversus abdominis (TrA)/internal oblique (IO), erector spinae (ES), and gluteus medius (GM) muscles were expressed relative to the electromyographic onset of the prime mover (i.e. soleus). Independent t-tests were performed to compare the onsets of each muscle between the groups. The nonparametric Friedman test and the post-hoc of Wilcoxon signed-rank test were used to describe the muscle activation pattern within the groups. RESULTS: The results revealed different recruitment patterns of the core muscles between the groups. In the healthy group the GM and TrA/IO contracted, almost simultaneously, in anticipation of the prime mover contraction (sol). However, in PFP subjects a significant delay in the contraction of TrA/IO changed the pattern of muscle activation. CONCLUSION: The findings demonstrate that muscular stabilization of spine is altered in the presence of PFP and suggest that treatment techniques aimed at improving core stability could be appropriate in the management of PFP. PMID- 26873797 TI - Hair Loss Induced by Chemotherapy: An Anthropological Study of Women, Cancer and Rehabilitation. AB - Throughout history hair has universally been a powerful symbol of the relationship between individuals and society, denoting religious affiliation, and has acted as a symbol of the social, cultural and political status quo. Hair loss, which is often perceived as a loss of individuality and attractiveness, has been related to the absence of status in these areas. The impact of hair loss on women undergoing chemotherapy treatment for cancer has primarily been explored by health professionals focusing on its psychological effects. This paper looks at women's experiences with hair loss induced by chemotherapy in a Danish context. It draws on an ethnographic fieldwork study comprising participant observation at three residential cancer rehabilitation courses in Denmark, subsequent in-depth interviews with some of the women and examination of written sources. The women equated hair loss with the loss of womanhood, sickness and death, and used wigs and make-up to minimize these effects. The analysis demonstrates how the women's embodied experiences are pervaded by culturally embedded signs, and how cancer rehabilitation is less concerned with total recovery in the sense of 'being cured' than with normalizing and integrating the individual in personal and social contexts. PMID- 26873793 TI - Asthma-Related School Absenteeism, Morbidity, and Modifiable Factors. AB - INTRODUCTION: Asthma is a leading cause of chronic disease-related school absenteeism. Few data exist on how information on absenteeism might be used to identify children for interventions to improve asthma control. This study investigated how asthma-related absenteeism was associated with asthma control, exacerbations, and associated modifiable risk factors using a sample of children from 35 states and the District of Columbia. METHODS: The Behavioral Risk Factor Surveillance System Child Asthma Call-back Survey is a random-digit dial survey designed to assess the health and experiences of children aged 0-17 years with asthma. During 2014-2015, multivariate analyses were conducted using 2006-2010 data to compare children with and without asthma-related absenteeism with respect to clinical, environmental, and financial measures. These analyses controlled for sociodemographic and clinical characteristics. RESULTS: Compared with children without asthma-related absenteeism, children who missed any school because of asthma were more likely to have not well controlled or very poorly controlled asthma (prevalence ratio=1.50; 95% CI=1.34, 1.69) and visit an emergency department or urgent care center for asthma (prevalence ratio=3.27; 95% CI=2.44, 4.38). Mold in the home and cost as a barrier to asthma-related health care were also significantly associated with asthma-related absenteeism. CONCLUSIONS: Missing any school because of asthma is associated with suboptimal asthma control, urgent or emergent asthma-related healthcare utilization, mold in the home, and financial barriers to asthma-related health care. Further understanding of asthma-related absenteeism could establish how to most effectively use absenteeism information as a health status indicator. PMID- 26873798 TI - A Healing Cult Met with the Baatombu from the North of Benin: The Kaawo. AB - Some remarkable studies have been devoted to the healing cults in Africa; but few of them focus on the role played by their therapeutic processes in the healing of the patient. This paper aims to show the real implication of the techniques mobilized in a healing process by a cult named Kaawo on the Baatombu in Northern Benin; and of which the data have been collected between 1995 and 2002. The outcomes of the study show the techniques used, such as prayer, sacrifice, divination, witchcraft, gesture and postures, as being real healing operators that have inductive properties with direct effect on the 'disease'. Here, the healing efficiency is all the more significant as the troubles from which the subjects suffer are either of psychosomatic or psychofunctional type, and relating rather to an existential malaise than an organic disorder. In this process, the priest/healer's conviction in the efficiency of the treatment prescribed to the patient, and the faith of the latter in the efficiency of the treatment received, maximize the potential of healing. It is clear that such results move away from the classical clinical approach that consists of assessing the consequences of a disease by examining symptoms it generates-and contributes to opening up some avenues for as yet fairly unexplored research opportunities. PMID- 26873799 TI - Maids, Migrants and Occupational Health in the London Sex Industry. AB - It has been argued that norms of occupational health have weakened with diversification in the sex industry. We explore this issue in walk-in flats in London, focusing on relationships between managers (maids) and sex workers. Today, most maids are local and most sex workers are 'migrants'. We collected data on 117 maids and sex workers, and carried out intensive fieldwork with seven maids and 17 sex workers. Managers take prime responsibility for educating and inducting new workers. Authoritarian management has been considered bad for health both in these walk-in flats and in the '100 per cent condom use programme' criticized by sex workers' projects. Yet, we found that maids acted as friends and managers, which helped settle new sex workers. Over time, however, migrants were more affected by issues of isolation and exploitation than local workers. Alternative models of health promotion such as peer education must be seen in a wider legal context where the lack of rights makes it difficult to appeal against exploitation, or to become mobile. PMID- 26873800 TI - Living Positively: Narrative Strategies of Women Living with HIV in Cape Town, South Africa. AB - Therapeutic interventions to address HIV in Africa mean that individuals are increasingly diagnosed with HIV prior to severe health crisis. This paper contributes to the anthropological literature on living with HIV by focusing on the creation and use of narrative and practical strategies for addressing HIV in a setting where such experiences have to date received little attention. Specifically, focus is on the discursive strategy of 'living positively', a forceful and much propagated orientation to life following an HIV diagnosis. In this paper the authors examine how this strategy is embraced not only by individuals living with HIV, but also by activists, HIV support organizations and public health agencies. The paper is based on fieldwork in and around Cape Town, South Africa in 2002 and draws on open-ended interviews with 12 women living with HIV and observations from support groups, activist events and public health meetings. The research indicates that the living positively dictum is imbued with a multiplicity of meanings and that it is used in diverse ways. For women living with HIV the practical and philosophical elements of positive living have social and political force in transforming personal and social attitudes about HIV, especially about HIV testing and treatment access. At the same time, however, the dictum poorly addresses the structural constraints of living with HIV and places the responsibility for positive living squarely on the individual. Despite this, the political context that prevailed in Cape Town at the time of the research created a particularly fertile juncture for embracing the living positively philosophy. PMID- 26873801 TI - Beyond PTSD: Socio-economic Bereavement in Tigray, Ethiopia. AB - By drawing upon data collected through in-depth interviews with 20 victims of the Ethio-Eritrean war, this paper addresses how psychosocial consequences of political war are expressed and conceptualized by people from Tigray, Ethiopia. War events were typically described in terms of their negative impacts on the household's means for income generation, and psychosocial complaints centred on aspects of impaired post-war economy rather than on politically violent experiences. The most reported complaints were (a) household erosion complaints, (b) social marginalization complaints and (c) education abortion complaints. Post war psychosocial health problems were perceived as consequences of these aspects of impaired household economy, and were described in terms of their negative impacts on future income generation. Informants' expressions of distress were found to be highly informed by the socio-cultural and socio-economic structures of the Tigrayan society. Being the only study of its kind from this context, the study provides a unique illustration of the limitations of western trauma measures and calls for a context-based conceptualization of trauma. PMID- 26873802 TI - Lay Explanations of Type 2 Diabetes in Bangkok, Thailand. AB - The increasing incidence of and mortality associated with type 2 diabetes in Thailand, and the lack of knowledge of lay understandings of diabetes, are the starting points of this paper. Ethnographic research was undertaken in an inner zone district of Bangkok, with participant observation, interviews and case studies conducted with individuals who had lived with type 2 diabetes for at least three years. Culturally specific explanations exist for the aetiology, pathology and course of illness, and responses to biomedical treatment. The notion of kam -the negative effects of past behaviour-underpinned participants' explanations of the cause of diabetes. The presentation and development of the disease derive from Thai traditional medical theory, but its management, aimed at controlling blood glucose levels and preventing complications, involves both cosmopolitan and traditional medicines. This syncretic approach to cause, diagnosis and management suggests the value of a more comprehensive approach in health education, diagnosis and treatment. PMID- 26873803 TI - Limits to Agency in Psychopathology: A Comparison of Trinidad and Albania. AB - Comparative anthropology at a distance is acceptable providing we use ethnographic findings to see how apparent similarities might actually differ in the field: 'aiming for comparison with the non-comparability of phenomena kept firmly in mind'. This paper contrasts the limits of agency in local understandings of 'psychopathology' for two societies: a fishing village in Trinidad and an agricultural mountain village in Albania. The work madness does in each reflects rather different histories and cultures-with a more dynamic and metaphorical resonance for the voluntarist Caribbean than for prescriptive Northern Albania. PMID- 26873804 TI - Reviews. PMID- 26873805 TI - Cerebral infarction following subcutaneous immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 26873806 TI - Beta- and gamma-band activity reflect predictive coding in the processing of causal events. AB - In daily life, complex events are perceived in a causal manner, suggesting that the brain relies on predictive processes to model them. Within predictive coding theory, oscillatory beta-band activity has been linked to top-down predictive signals and gamma-band activity to bottom-up prediction errors. However, neurocognitive evidence for predictive coding outside lower-level sensory areas is scarce. We used magnetoencephalography to investigate neural activity during probability-dependent action perception in three areas pivotal for causal inference, superior temporal sulcus, temporoparietal junction and medial prefrontal cortex, using bowling action animations. Within this network, Granger causal connectivity in the beta-band was found to be strongest for backward top down connections and gamma for feed-forward bottom-up connections. Moreover, beta band power in TPJ increased parametrically with the predictability of the action kinematics-outcome sequences. Conversely, gamma-band power in TPJ and MPFC increased with prediction error. These findings suggest that the brain utilizes predictive-coding-like computations for higher-order cognition such as perception of causal events. PMID- 26873808 TI - Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register. AB - BACKGROUND: Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register. METHODS: We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome. FINDINGS: We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex standardised mortality ratios (SMRs) for all-cause mortality (SMR 1.14, 95% CI 0.65-1.85; p=0.67) or cancer-specific mortality (1.39, 0.60-2.73; p=0.45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6.85, 95% CI 2.22-15.98; p=0.002). INTERPRETATION: We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome. FUNDING: National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. PMID- 26873807 TI - Association between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study. AB - Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B= 0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia. PMID- 26873809 TI - Suicide risk in people with chronic fatigue syndrome. PMID- 26873810 TI - Survival and overall treatment time after postoperative radio(chemo)therapy in patients with head and neck cancer. AB - BACKGROUND: Generally, overall treatment time for patients with locally advanced head and neck cancer should be as short as reasonably possible. This analysis was undertaken to determine at what overall treatment time additional survival/locoregional control benefits could be achieved compared to a 100-day cutoff. METHODS: Clinical impact of overall treatment time was assessed in 272 patients by multivariable Cox regression and Kaplan-Meier analyses using the historical 100-day cutoff and the optimal overall treatment time, determined using recursive partitioning analysis. Survival endpoints were determined for the 100-day and optimal overall treatment times validated using bootstrap resampling. RESULTS: Recursive partitioning determined the optimal overall treatment time as 87 days. In the 87-day multivariable analysis, adverse factors for overall survival (OS) and disease-free survival (DFS) were overall treatment time >=87 days and extracapsular spread, and overall treatment time and R1 status, respectively. CONCLUSION: Overall treatment time is important for survival in patients with head and neck cancer. Completing treatment within as short a timeframe as possible may be associated with longer OS and DFS. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1058-1065, 2016. PMID- 26873811 TI - 'Candidatus Rickettsia mendelii', a novel basal group rickettsia detected in Ixodes ricinus ticks in the Czech Republic. AB - A novel rickettsial sequence in the citrate synthase gltA gene indicating a novel Rickettsia species has been detected in 7 out of 4524 Ixodes ricinus ticks examined within several surveys performed in the Czech Republic from 2005 to 2009. This new Candidatus Rickettsia sp. sequence has been found in 2 nymphs feeding on wild birds (Luscinia megarhynchos and Erithacus rubecula), in a male tick from vegetation, and 4 ticks feeding on a dog (3 males, 1 female tick). Portions of the ompA, ompB, sca4, and htrA genes were not amplifiable in these samples. A maximum likelihood tree of rickettsiae based on comparisons of partial amino acid sequences of citrate synthase and nucleotide sequences of 16S rDNA genes and phylogenetic analysis revealed a basal position of the novel species in the proximity of R. bellii and R. canadensis. The novel species has been named 'Candidatus Rickettsia mendelii' after the founder of genetics, Gregor Mendel. PMID- 26873812 TI - High-throughput-sequencing-based identification of a grapevine fanleaf virus satellite RNA in Vitis vinifera. AB - A new satellite RNA (satRNA) of grapevine fanleaf virus (GFLV) was identified by high-throughput sequencing of high-definition (HD) adapter libraries from grapevine plants of the cultivar Panse precoce (PPE) affected by enation disease. The complete nucleotide sequence was obtained by automatic sequencing using primers designed based on next-generation sequencing (NGS) data. The full-length sequence, named satGFLV-PPE, consisted of 1119 nucleotides with a single open reading frame from position 15 to 1034. This satRNA showed maximum nucleotide sequence identity of 87 % to satArMV-86 and satGFLV-R6. Symptomatic grapevines were surveyed for the presence of the satRNA, and no correlation was found between detection of the satRNA and enation symptom expression. PMID- 26873813 TI - Serological survey of hepatitis E virus infection in farmed and pet rabbits in Italy. AB - The recent identification in rabbits of hepatitis E viruses (HEV) related to viruses infecting humans raises the question of the role of this species as possible HEV reservoir. A serological survey on rabbit HEV infection was conducted in Italy during 2013-2014, including both farmed and pet rabbits. We found an anti-HEV antibody seroprevalence of 3.40 % in 206 farmed rabbits (collected on 7 farms) and 6.56 % in 122 pets. RNA was extracted from IgG positive sera and analyzed by HEV-specific real-time RT-PCR. None of the samples were positive, confirming that no viremia was present in the presence of IgG. Only one serum sample from a farmed rabbit was positive for IgM, but no HEV RNA was detected in it. Pet rabbit feces were also tested for HEV RNA, with negative results. This finding suggests that HEV is circulating in rabbits in Italy. PMID- 26873814 TI - The unique role of the hepatitis virus B X protein on HEK 293 cell morphology and cellular change. AB - The function of the hepatitis B virus X protein (HBx) has been investigated in hepatoma cell lines before; however, its function in the canonical HEK 293 cell line has not been addressed. In this study, we found that HBx increased cellular interaction by fusing the gap between HEK 293 cells, which is different from what has been reported previously. We also found that HBx enhanced the expression of E cadherin in hepatoma cell lines instead of decreasing it as reported previously. The increase in E-cadherin was mediated by the enhanced levels of Src, which also differs from previous reports. Finally, we observed that HBx can accelerate cell growth by increasing the percentage of cells that are positioned at the division stage. Further analysis showed that the increased growth was caused by increased CDK4 expression and Ki67(+) populations. Additionally, reduced apoptosis was found in HEK 293 cells expressing HBx due to an increase in the anti-apoptotic protein-Bcl2. Collectively, the different functions of HBx in HEK 293 cells suggest that its role is cell dependent. PMID- 26873815 TI - Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge. AB - Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV. PMID- 26873816 TI - Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis. AB - BACKGROUND: No formal systematic review or meta-analysis was performed up to now to summarize the risk factors of delirium after hip surgery. AIMS: The present study aimed to quantitatively and comprehensively conclude the risk factors of delirium after hip surgery in elderly patients. METHODS: A search was applied to CNKI, Embase, Medline, and Cochrane central database (all up to August 2015). All studies assessing the risk factors of delirium after hip surgery in elderly patients without language restriction were reviewed, and qualities of included studies were assessed using the Newcastle-Ottawa Scale. Data were pooled and a meta-analysis was completed. RESULTS: A total of 24 studies were selected, which altogether included 5364 patients with hip fracture. One thousand and ninety of them were cases of delirium occurred after surgery, suggesting the accumulated incidence of 24.0 %. Results of meta-analyses showed that elderly patients with preoperative cognitive impairment [odds ratio (OR) 3.21, 95 % confidence interval (CI) 2.26-4.56), advanced age (standardized mean difference 0.50, 95 % CI 0.33 0.67), living in an institution (OR 2.94; 95 % CI 1.65-5.23), heart failure (OR 2.46; 95 % CI 1.72-3.53), total hip arthroplasty (OR 2.21; 95 % CI 1.16-4.22), multiple comorbidities (OR 1.37; 95 % CI 1.12-1.68) and morphine usage (OR 3.01; 95 % CI 1.30-6.94) were more likely to sustain delirium after hip surgery. Females were less likely to develop delirium after hip surgery (OR 0.83; 95 % CI 0.70-0.98). CONCLUSIONS: Related prophylaxis strategies should be implemented in elderly patients involved with above-mentioned risk factors to prevent delirium after hip surgery. PMID- 26873817 TI - How the knowledge of fracture risk might influence adherence to oral therapy of osteoporosis in Italy: the ADEOST study. AB - The patients' adherence to osteoporosis treatments is low. In our study population a history of osteoporotic fractures was associated to better compliance and persistence; however, a 12-month randomized study carried out on 816 osteoporotic women showed that providing the patients with their individual fracture risk information did not prove effective. PURPOSE: Several drugs are currently available for the treatment of osteoporosis, but the patients' compliance and persistence with these treatments are low. This study aimed to both analyze the adherence to oral osteoporosis medications among Italian osteoporotic patients (cross-sectional study) and evaluate if providing patients with their individual fracture risk information may improve compliance and persistence (prospective study). METHODS: A total of 3379 osteoporotic patients referred as outpatients for a visit 1 year after receiving a prescription of oral osteoporosis medications for the first time, were enrolled for the retrospective study. Moreover, 816 postmenopausal women receiving an oral prescription for osteoporosis for the first time, were randomized into two groups: group 1 (managed according to standard clinical practice) and group 2 (managed with greater patient involvement and information on the individual risk of major osteoporotic fractures calculated by DeFRA algorithm). RESULTS: In the retrospective study, a history of osteoporotic fractures, the frequency of drug administration and a condition of being overweight/obese had a significant influence on both compliance and persistence. Of the 816 patients enrolled in the longitudinal study, 731 (374 of group 1 and 357 of group 2) attended the 1 year follow-up visit. The percentage of women with high compliance or persistence was greater in group 2 (64.2 vs. 58.1 % and 66.8 vs. 62.6 %, respectively), but without reaching any statistical significance. CONCLUSIONS: Although providing the patients with their individual fracture risk information was not statistically effective, further studies on additional interventions able to improve the patients' perceived risk of fracture are warranted. PMID- 26873818 TI - Clinical presentation, management and outcomes of Staph aureus bacteremia (SAB) in older adults. AB - AIM: The incidence of Staphylococcus aureus bacteremia (SAB) increases with advancing age with higher mortality reported in older adults. We aimed to describe the clinical presentation, management and outcomes of older patients with SAB. METHODS: We analyzed data from a retrospectively collected database including 1692 patients with SAB, and compared 1158 older patients (>=65 years) with 534 younger patients (<65 years) in terms of clinical features, management of infection, and outcomes. RESULTS: Older patients were significantly less likely to be febrile on presentation, with 37.5 % (415/1106) of older patients presenting with normal body temperature [versus 29.2 % (152/520) of younger patients]. Older patients were however, more likely to have leukocytosis, septic shock, lower heart rate and lower diastolic blood pressure compared with younger patients. Management of older patients included significantly less imaging studies, performance of transesophageal echocardiogram (TEE) and infectious diseases consultation. TEE was performed less in older patients [124/726 (17.1 %) versus 72/285 (25.3 %)]. Mortality was significantly higher in older patients [550/1158 (47.5 %) versus 124/534 (23.2 %)], with predictors for mortality for the entire cohort in multivariate analysis including older age, higher Charlson comorbidity index, female sex, impaired functional capacity, pneumonia or primary bacteremia, and non-performance of TEE. CONCLUSIONS: Mortality rates in older patients with SAB are higher compared with younger patients. Several diagnostic and therapeutic procedures in the management of SAB were less likely to be performed in older patients in our cohort. These may have implications on outcome and should not be dismissed on the basis of age alone. PMID- 26873819 TI - Long-term exposure to gold nanoparticles accelerates larval metamorphosis without affecting mass in wood frogs (Lithobates sylvaticus) at environmentally relevant concentrations. AB - Nanoparticles are environmental contaminants of emerging concern. Exposure to engineered nanoparticles has been shown to have detrimental effects on aquatic organisms. The authors synthesized gold nanoparticles (18.1 +/- 3.5 nm) and tested their effects on time to and weight at metamorphosis in wood frog (Lithobates sylvaticus) tadpoles, a species known to be sensitive to environmental stressors. Continuous exposure to all concentrations of gold nanoparticles (0.05 pM, 0.5 pM, and 5 pM in particles) for up to 55 d significantly reduced time to metamorphosis by as much as an average of 3 d (p < 0.05). However, exposure to gold nanoparticles had no effect on tadpole mass at metamorphosis. The approximately 18-nm gold nanoparticles used were metastable in dechlorinated tap water, resulting in a change in surface charge and aggregation over time, leading to negatively charged aggregates that were on the order of 60 nm to 110 nm. Nanoparticle aggregation could exacerbate the effect on time to metamorphosis. To the authors' knowledge, the present study is the first report on the effect of engineered nanoparticles of any kind on life-history variables in an amphibian, a taxonomic group that has been declining globally for at least 25 yr. Environ Toxicol Chem 2016;35:2304-2310. (c) 2016 SETAC. PMID- 26873820 TI - Metabolic fate of milk glycosaminoglycans in breastfed and formula fed newborns. AB - In this study, the content, structure and residual percentages of glycosaminoglycans (GAGs) in the feces of seven breastfed newborns after ingesting a known amount of milk were studied. A comparison was made with five newborns fed with formula milk. Characterization of GAGs from milk and feces samples was performed according to previous methodology. Compared to the ingested GAGs present in milk, residual feces GAGs of breastfed newborns were <0.4 %, contrary to formula milk fed children, where the residues were ~4 %. As a consequence, >99 % of human milk GAGs are utilized as opposed to ~96 % of formula milk. Hyaluronic acid utilization was found to be fairly similar contrary to chondroitin sulfate/dermatan sulfate and heparan sulfate, which were found to be ~10-18 times lower in formula milk fed children. Our new results further demonstrate that the elevated content of human milk GAGs passes undigested through the entire digestive system of newborns, possibly protecting the infant from infections. In the distal gastrointestinal tract, these complex macromolecules are catabolized by a cohort of bacterial enzymes and constituent monosaccharides/oligosaccharides utilized for further metabolic purposes potentially useful for bacteria metabolism or internalized by intestinal cells. Thanks to their elevated structural heterogeneity, milk GAGs are used differently depending on their distinct primary structure. Finally, a different utilization and availability was observed for human milk GAGs compared to formula milk due to their various composition and structural heterogeneity. PMID- 26873821 TI - Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation. AB - Congenital disorder of glycosylation (CDG), formerly representing a group of diseases due to defects in the biosynthetic pathway of protein N-glycosylation, currently covers a wide range of disorders affecting glycoconjugates. Since its first application to serum transferrin from a CDG patient with phosphomannomutase 2 deficiency in 1992, mass spectrometry (MS) has been playing a key role in identification and characterization of glycosylation defects affecting glycoproteins. MS of native transferrin detects a lack of glycans characteristic to the classical CDG-I type of molecular abnormality. Electrospray ionization MS of native transferrin, especially, allows glycoforms to be analyzed precisely but requires basic knowledge regarding deconvolution of multiply-charged ions which may generate ghost signals upon transformation into a singly-charged form. MS of glycopeptides from tryptic digestion of transferrin delineates site-specific glycoforms and reveals a delicate balance of donor/acceptor substrates or the conformational effect of nascent proteins in cells. Matrix-assisted laser desorption ionization MS of apolipoprotein C-III is a simple method of elucidating the profiles of mucin-type core 1 O-glycans including site occupancy and glycoforms. In this technological review, the principle and pitfalls of MS for CDG are discussed and mass spectra of various types of CDG are presented. PMID- 26873823 TI - Toxicity assessment of silver nanoparticles in Persian sturgeon (Acipenser persicus) and starry sturgeon (Acipenser stellatus) during early life stages. AB - Silver nanoparticles (AgNPs) are widely used in consumer products mainly due to their antimicrobial action. The rapidly increasing use of nanoparticles (NPs) has driven more attention to their possible ecotoxicological effects. In this study, the acute toxicity of colloidal AgNPs was evaluated during the embryonic stage of Persian sturgeon (Acipenser persicus) and starry sturgeon (Acipenser stellatus) at concentrations of 0, 0.25, 0.5, 1, 2, 4, and 8 mg/L. Fertilized eggs (75 eggs per replicate) were exposed to aforementioned concentrations for 96 h in triplicate. 96-h LC50 values in Persian sturgeon and starry sturgeon were calculated as 0.163 and 0.158 mg/L, respectively. Furthermore, in starry sturgeon, the short-term effects of AgNPs on the hatching rate, survival rate, and Ag accumulation during early life stages (before active feeding commences) were also analyzed at concentrations of 0, 0.025, 0.05, and 0.1 mg/L of colloidal AgNPs. The highest silver accumulation occurred in larvae exposed to 0.1 mg/L AgNPs; however, the body burden of silver did not alter survival rate, and there were no significant differences among treatments. Based on the obtained results from the acute toxicity exposures, AgNPs induced a concentration-dependent toxicity in both species during early life stages, while complementary studies are suggested for investigating their short-term effects in detail. PMID- 26873824 TI - Metal contamination at recreational boatyards linked to the use of antifouling paints-investigation of soil and sediment with a field portable XRF. AB - The application of a field portable X-ray fluorescence spectrometer (FPXRF) to measure Cu, Zn, and Pb in soil and sediments at recreational boatyards by Lake Malaren in Sweden was investigated. Confirmatory chemical analysis on freeze dried samples shows that, ex situ, the FPXRF produces definitive level data for Cu and Zn and quantitative screening data for Pb, according to USEPA criteria for data quality. Good agreement was also found between the ex situ measurements and the in situ screening. At each of the two studied boatyards, >40 in situ soil measurements were carried out. Statistical differences in soil concentration based on land use were consequently found: the areas used for boat storage and maintenance were significantly higher in Cu and Zn than the areas used for car parking and transportation. The metal pollution in the boat storage areas is therefore shown to be directly linked to hull maintenance activities during which metal-containing antifouling paint particles are shed, end up on the ground, and consequently pollute the soil. In the boat storage areas, the Cu and Zn concentrations often exceeded the national guideline values for soil. In this study, they were also shown to increase with increasing age of the boatyard operation. Pb soil concentrations were only elevated at a few measurement points, reflecting the phasing out of Pb compounds from antifouling products over the past 2 decades. In the surface sediments, concentrations of Cu and Zn were 2-3 times higher compared to deeper levels. No decrease in metal concentration with time was found in the sediments, indicating that boat owners are not complying with the ban of biocide-containing paints in freshwater introduced over 20 years ago. PMID- 26873825 TI - Cold homes are associated with poor biomarkers and less blood pressure check-up: English Longitudinal Study of Ageing, 2012-2013. AB - It has been known that outdoor temperature influences seasonal fluctuation of blood pressure and cholesterol levels, but the role of indoor temperature has been less studied. Therefore, the aim of the present study was to examine the associations between indoor temperature and biomarkers in a countrywide and population-based setting. Data was retrieved from the English Longitudinal Study of Ageing, 2012-2013. Information on demographics, room temperature and a series of biomarkers measured in the blood and lung was obtained at household interviews. t test, chi-square test and a generalized linear model were performed cross-sectionally. Of 7997 older adults with the valid indoor temperature measurements, there were 1301 (16.3%) people who resided in cold homes (<18 degrees C). Age was inversely associated with people who resided in cold homes or who tended not to have blood pressure check-up. Those who resided in cold homes had higher blood pressure readings, worse handgrip, lower vitamin D levels, higher cholesterol levels, higher insulin-like growth factor levels, higher haemoglobin levels, lower level of white blood cell count and worse lung conditions. One in six older adults aged 50 and above in England resided in cold homes and had poor biomarker values. For the future research direction, studies with a longitudinal approach to systematically monitor indoor temperature, biomarkers and health and wellbeing would be suggested. From the practice and policy perspectives, increasing health knowledge on the adverse effect of low indoor temperature on risks of cardiac and respiratory conditions, affording to the heating and re-designing of residential buildings to keep warm by using efficient energy, should be kept as priority. PMID- 26873826 TI - Synergism in the desorption of polycyclic aromatic hydrocarbons from soil models by mixed surfactant solutions. AB - This study investigates the effect of a mixed surfactant system on the desorption of polycyclic aromatic hydrocarbons (PAHs) from soil model systems. The interaction of a non-ionic surfactant, Tween 80, and an anionic one, sodium laurate, forming mixed micelles, produces several beneficial effects, including reduction of adsorption onto solid of the non-ionic surfactant, decrease in the precipitation of the fatty acid salt, and synergism to solubilize PAHs from solids compared with individual surfactants. PMID- 26873822 TI - Sickle Cell Disease and Stroke: Diagnosis and Management. AB - Both adult and pediatric patients with sickle cell disease face a higher risk of stroke than the general population. Given the different underlying pathophysiology predisposing these patients to stroke, providers should be aware of differences in guidelines for stroke management. This paper reviews diagnostic considerations and recommendations during the evaluation and acute management of patients with sickle cell disease presenting with stroke, focusing on recent updates in the literature. Given the high recurrence rate of stroke in these patients, secondary prevention and curative measures will also be reviewed. PMID- 26873828 TI - Photoinitiators enhanced 1,2-dichloropropane-induced cytotoxicity in human normal embryonic lung fibroblasts cells in vitro, Yoichi Kawasaki, Chiaki Tsuboi, Kenta Yagi, Miwa Morizane, Yasuyuki Masaoka, Satoru Esumi, Yoshihisa Kitamura, Toshiaki Sendo (2014) Environ Sci Pollut Res 22: 4763-4770 ; DOI: 10.1007/s11356-014-3939 8. PMID- 26873827 TI - Interspecific variation in the diets of herbivores in an industrial environment: implications for exposure to fluoride emissions. AB - Atmospheric fluorides (gaseous and particulate) are deposited on, and absorbed by, vegetation. Ingested fluoride accumulates in calcified tissues of vertebrates, and if it is excessive, it may lead to dental and skeletal fluorosis. The prevalence, form and severity of the effects vary greatly between species. Foraging strategy can be an important determinant of fluoride exposure in herbivores, because foliar fluoride concentrations vary between plant species, for example, according to vertical and lateral position in the vegetation. We combined microhistological analysis of diet and analysis of foliar fluoride levels to examine interspecific variation in dietary fluoride exposure of macropodid marsupials (swamp wallaby Wallabia bicolor, red-necked wallaby Notamacropus rufogriseus and eastern grey kangaroo Macropus giganteus), in the buffer zone of an aluminium smelter in Victoria, Australia. Dietary niche differentiation between species was evident. The swamp wallaby and the red-necked wallaby were browsers or mixed feeders, depending on the classification system used. The eastern grey kangaroo was a grazer, consuming almost entirely grasses. However, foliar fluoride did not vary significantly between the main plant groups consumed. Our results indicate that interspecific variation in diet at this site is unlikely to explain variation in fluoride exposure. PMID- 26873829 TI - Comparison and mechanism of photocatalytic activities of N-ZnO and N-ZrO2 for the degradation of rhodamine 6G. AB - N-doped ZnO (N-ZnO) and N-doped ZrO2 (N-ZrO2) are synthesized by novel, simple thermal decomposition methods. The catalysts are evaluated for the degradation of rhodamine 6G (R6G) under visible and UV light. N-ZnO exhibits higher dye degradation under both visible and UV light compared to N-ZrO2 due to possessing higher specific surface area, lower crystalline size, and lower band gap. However, it is less reusable than N-ZrO2 and its photocatalytic activity is also deteriorated at low pH. At the same intensity of 3.5 W/m(2), UVC light is shown to be a better UV source for N-ZnO, while UVA light is more suitable for N-ZrO2. At pH 7 with initial dye concentration of 10 mg/L, catalyst concentration of 1 g/L, and UVC light, 94.3 % of R6G is degraded by N-ZnO within 2 h. Using UVA light under identical experimental conditions, 93.5 % degradation of R6G is obtained by N-ZrO2. Moreover, the type of light source is found to determine the reactive species produced in the R6G degradation by N-ZnO and N-ZrO2. Less oxidative reactive species such as superoxide radical and singlet oxygen play a major role in the degradation of R6G under visible light. On the contrary, highly oxidative hydroxyl radicals are predominant under UVC light. Based on the kinetic study, the adsorption of R6G on the catalyst surface is found to be the controlling step. PMID- 26873831 TI - Reevaluating excess success in psychological science. AB - Francis (Psychonomic Bulletin Review, 21, 1180-1187, 2014) recently claimed that 82 % of articles with four or more experiments published in Psychological Science between 2009 and 2012 cannot be trusted. We critique Francis' analysis and point out the dependence of his approach on including the appropriate experiments and significance tests. We focus on one of the articles (van Boxtel & Koch, in Psychological Science, 23(4), 410-418, 2012) flagged by Francis and show that the inappropriate inclusion of experiments and tests have led Francis to mistakenly flag this article. We found that decisions about whether to include certain tests potentially affect 34 of the 44 articles analyzed by Francis. We further performed p-curve analyses on the articles discussed in Francis' analysis. We found that 9 of 44 studies showed significant evidential value, 11 studies showed insufficient evidential value, and 1 study showed evidence of p-hacking. Our reevaluation is important, because some researchers may have gained the false impression that none of the quoted articles in Psychological Science can be trusted (as stated by Francis). The analysis by Francis is most likely insufficient to warrant this conclusion for some articles and certainly is insufficient with respect to the study by van Boxtel and Koch (Psychological Science, 23, 410-418, 2012). PMID- 26873832 TI - Effects of extracorporeal carbon dioxide removal on work of breathing in patients with chronic obstructive pulmonary disease. PMID- 26873830 TI - Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status. AB - INTRODUCTION: Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. METHODS: Gadolinium deposition in the brain following repeated CE MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. RESULTS: Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. CONCLUSION: Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. PMID- 26873834 TI - Understanding the venous-arterial CO2 to arterial-venous O2 content difference ratio. PMID- 26873835 TI - Association of prior antiplatelet agents with mortality in sepsis patients. PMID- 26873833 TI - Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum. AB - Catecholamines are endogenous neurosignalling mediators and hormones. They are integral in maintaining homeostasis by promptly responding to any stressor. Their synthetic equivalents are the current mainstay of treatment in shock states to counteract myocardial depression and/or vasoplegia. These phenomena are related in large part to decreased adrenoreceptor sensitivity and altered adrenergic signalling, with resultant vascular and cardiomyocyte hyporeactivity. Catecholamines are predominantly used in supraphysiological doses to overcome these pathological consequences. However, these adrenergic agents cause direct organ damage and have multiple 'off-target' biological effects on immune, metabolic and coagulation pathways, most of which are not monitored or recognised at the bedside. Such detrimental consequences may contribute negatively to patient outcomes. This review explores the schizophrenic 'Jekyll-and-Hyde' characteristics of catecholamines in critical illness, as they are both necessary for survival yet detrimental in excess. This article covers catecholamine physiology, the pleiotropic effects of catecholamines on various body systems and pathways, and potential alternatives for haemodynamic support and adrenergic modulation in the critically ill. PMID- 26873836 TI - Natural History of Renal Angiomyolipoma (AML): Most Patients with Large AMLs >4cm Can Be Offered Active Surveillance as an Initial Management Strategy. AB - BACKGROUND: The natural history of renal angiomyolipoma (AML) is unknown. Treatment recommendations are based on smaller case series, with selection bias towards symptomatic patients. OBJECTIVE: To define the natural history of renal AML, including growth rates, size, and clinical presentation. DESIGN, SETTING, AND PARTICIPANTS: We used a unique radiology data-mining system (Montage; Montage Healthcare Systems, Philadelphia, PA, USA) to retrospectively review the radiology database in an academic health centre between 2002 and 2013 to identify all renal AMLs. Of 2741 patients identified, 447 with 582 AMLs had three or more imaging studies suitable for analysis. INTERVENTION: Angioembolisation, surgery, radiofrequency ablation, and mammalian target of rapamycin inhibitors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was the growth rate of untreated AMLs. We used a linear mixed-effects model to determine change in growth rate over time. We evaluated the association among growth rate, size, and patient factors as well as interventions. RESULTS AND LIMITATIONS: The majority of untreated AMLs (>92%) had not grown at a median follow-up of 43 mo, with no difference in growth rates between AMLs <=4 and >4cm. Most AMLs occurred in female participants (80%) and were asymptomatic (91%). Tuberous sclerosis complex (TSC) was confirmed in 3.8% (n=17) and presented at an earlier age. Median size was 1cm but was significantly larger for TSC (5.5cm; p<0.001). Interventions were performed in 5.6% of patients. Limitations of our study include the retrospective design, selection against fat-poor AMLs, and lack of histology. CONCLUSIONS: This large, single-institution series on AMLs confirms that lesions >4cm do not require early intervention based on size alone. The vast majority are sporadic, asymptomatic, and initially harmless, with a negligible growth rate. Our findings support a policy of initial active surveillance for all asymptomatic AMLs. PATIENT SUMMARY: We evaluated the natural history and growth rates of renal AMLs. We found no difference in growth rates between AMLs >4 and <=4cm. Initial AS appears to be a safe management option. PMID- 26873837 TI - Reply from Authors re: Matthew T. Gettman. Assessing Work Disability After Radical Prostatectomy. Eur Urol 2016;70:72-3: The Challenge of Assessing Work Disability. PMID- 26873838 TI - Re: Neil E. Martin, Laura Massey, Caleb Stowell, et al. Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer. Eur Urol 2015;67:460-7. PMID- 26873839 TI - Complete Responses with Targeted Therapy in Metastatic Renal Cell Carcinoma: Balancing Efficacy and Toxicity. PMID- 26873840 TI - Chemohyperthermia with Mitomycin-C Compared with Bacillus Calmette-Guerin: A "Hot" Topic. PMID- 26873841 TI - Diagnostic and Therapeutic Implications of Erectile Dysfunction in Patients with Cardiovascular Disease. AB - Erectile dysfunction (ED) and cardiovascular disease (CVD) share many common pathophysiologic pathways and might be regarded as two different clinical manifestations of the same systemic disease. Consequently, ED and CVD are pathologic conditions that often coexist in the same patient. The urologist plays an important role in the management of ED in patients with a history of cardiovascular events. Therapeutic measures aimed at improving sexual function in CVD patients should be considered only after careful evaluation of the underlying cardiologic condition and assessment of ability to exercise. Sexual activity and treatment of ED might trigger cardiac events in selected patients with preexisting CVD; therefore, proerectile therapies should be administered only to low-risk patients for whom subsequent risk of cardiac events would not be increased. Conversely, men at high risk of CVD should receive cardiologic reassessment and stabilization before attempting sexual activity and receiving ED treatment. Risk reduction and lifestyle changes, administration of phosphodiesterase type 5 inhibitors, and testosterone replacement therapy, as indicated, might provide benefits not only in terms of improving sexual function but also for reducing the risk of future cardiac events. PATIENT SUMMARY: Erectile dysfunction (ED) and cardiovascular disease (CVD) share many pathophysiologic mechanisms and often coexist in the same patient. We evaluated the role of the urologist in the management of ED in patients with preexisting CVD and the impact of measures aimed at improving sexual function on the subsequent risk of cardiac events. PMID- 26873842 TI - Ruffling the Immunotherapy Response Paradigm with a Novel Personalized Peptide Vaccine. PMID- 26873843 TI - Reply to Daniela Wittmann, Ted A. Skolarus' Letter to the Editor re: Neil E. Martin, Laura Massey, Caleb Stowell, et al. Defining a Standard Set of Patient centered Outcomes for Men with Localized Prostate Cancer. Eur Urol 2014;67:460-7. PMID- 26873844 TI - The NHS Health Checks programme: A better alternative. PMID- 26873846 TI - Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients. AB - In pancreatic ductal adenocarcinomas (PDAC), lymphoid infiltrates, comprised mainly of Th2 cells, predict a poor survival outcome in patients. IL4 signaling has been suggested to stabilize the Th2 phenotype in this setting, but the cellular source of IL4 in PDAC is unclear. Here, we show that basophils expressing IL4 are enriched in tumor-draining lymph nodes (TDLN) of PDAC patients. Basophils present in TDLNs correlated significantly with the Th2/Th1 cell ratio in tumors, where they served as an independent prognostic biomarker of patient survival after surgery. Investigations in mouse models of pancreatic cancer confirmed a functional role for basophils during tumor progression. The recruitment of basophils into TDLN relied partly upon the release of chemokine CCL7/MCP3 by "alternatively activated" monocytes, whereas basophil activation was induced by T-cell-derived IL3. Our results show how basophils recruited and activated in TDLNs under the influence of the tumor microenvironment regulate tumor-promoting Th2 inflammation in PDAC, helping in illuminating a key element of the immune milieu of pancreatic cancer. Cancer Res; 76(7); 1792-803. (c)2016 AACR. PMID- 26873845 TI - Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. AB - Multiple myeloma is a fatal plasma cell neoplasm accounting for over 10,000 deaths in the United States each year. Despite new therapies, multiple myeloma remains incurable, and patients ultimately develop drug resistance and succumb to the disease. The response to selective CDK4/6 inhibitors has been modest in multiple myeloma, potentially because of incomplete targeting of other critical myeloma oncogenic kinases. As a substantial number of multiple myeloma cell lines and primary samples were found to express AMPK-related protein kinase 5(ARK5), a member of the AMPK family associated with tumor growth and invasion, we examined whether dual inhibition of CDK4 and ARK5 kinases using ON123300 results in a better therapeutic outcome. Treatment of multiple myeloma cell lines and primary samples with ON123300 in vitro resulted in rapid induction of cell-cycle arrest followed by apoptosis. ON123300-mediated ARK5 inhibition or ARK5-specific siRNAs resulted in the inhibition of the mTOR/S6K pathway and upregulation of the AMPK kinase cascade. AMPK upregulation resulted in increased SIRT1 levels and destabilization of steady-state MYC protein. Furthermore, ON123300 was very effective in inhibiting tumor growth in mouse xenograft assays. In addition, multiple myeloma cells sensitive to ON123300 were found to have a unique genomic signature that can guide the clinical development of ON123300. Our study provides preclinical evidence that ON123300 is unique in simultaneously inhibiting key oncogenic pathways in multiple myeloma and supports further development of ARK5 inhibition as a therapeutic approach in multiple myeloma. PMID- 26873847 TI - Identification and characterization of HolGH15: the holin of Staphylococcus aureus bacteriophage GH15. AB - Holins are phage-encoded hydrophobic membrane proteins that spontaneously and non specifically accumulate and form lesions in the cytoplasmic membrane. The ORF72 gene (also designated HolGH15) derived from the genome of the Staphylococcus aureus phage GH15 was predicted to encode a membrane protein. An analysis indicated that the protein encoded by HolGH15 potentially consisted of two hydrophobic transmembrane helices. This protein exhibited the structural characteristics of class II holins and belonged to the phage_holin_1 superfamily. Expression of HolGH15 in Escherichia coli BL21 cells resulted in growth retardation of the host cells, which was triggered prematurely by the addition of 2,4-dinitrophenol. The expression of HolGH15 caused morphological alterations in engineered E. coli cells, including loss of the cell wall and cytoplasmic membrane integrity and release of intracellular components, which were visualized by transmission electron microscopy. HolGH15 exerted efficient antibacterial activity at 37 degrees C and pH 5.2. Mutation analysis indicated that the two transmembrane domains of HolGH15 were indispensable for the activity of the full length protein. HolGH15 showed a broad antibacterial range: it not only inhibited Staphylococcus aureus, but also demonstrated antibacterial activity against other species, including Listeria monocytogenes, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumoniae and E. coli. At the minimal inhibitory concentration, HolGH15 evoked the release of cellular contents and resulted in the shrinkage and death of Staphylococcus aureus and Listeria monocytogenes cells. To the best of our knowledge, this study is the first report of a Staphylococcus aureus phage holin that exerts antibacterial activity against heterogeneous pathogens. PMID- 26873848 TI - Estrogen Downregulates miR-21 Expression and Induces Inflammatory Infiltration of Macrophages in Polymyositis: Role of CXCL10. AB - This study was aimed to explore the role of estrogen in inducing inflammatory infiltration of macrophages in polymyositis (PM) through downregulation of miR 21, which could further inhibit the expression of C-X-C motif chemokine 10 (CXCL10). Biopsies were collected from 20 PM patients before and after treatment of glucocorticoid. Additionally, peritoneal macrophages were isolated from male SD model rats (n = 40). Creatine kinase (CK) and CXCL10 and nuclear factor-kappa (NF-kappaB) expressions were tested using immunosorbent and immunocytochemical assays. We also conducted transwell assay to observe invasive abilities of cells; RT-PCR and western blot were intended to semi-quantify miR-21 and CXCL10 expressions in vitro and in vivo. Compared with the control group, serum creatine kinase (S-CK) was upregulated in PM subjects, but its content decreased after treatment of immunosuppressive substances (e.g., glucocorticoids). Moreover, hormone treatment can significantly increase miR-21 expressions in PM patients (P < 0.05). However, CXCL10 expressions had an opposite tendency compared to miR 21expressions. Results drawn from rat model were consistent with those discovered in PM patients. Moreover, miR-21 transfection could significantly decrease the relative luciferase activity when it was integrated with CXCL10 3'-untranslated region (3'-UTR) in macrophage. Estrogen treatment can also upregulate the expression of NF-kappaB in macrophage nucleus. Nonetheless, the upregulated tendency was inhibited by either miR-21 mimics or anti-CXCL10 mAb (P < 0.05). Both macrophage migration and CXCL10 expressions were significantly decreased after applying miR-21 treatments compared with the control group, yet estrogen could enhance macrophage migration and increase CXCL10 expressions (P < 0.05). Immune inhibitors such as glucocorticoids can significantly downregulate miR-21 and upregulate CXCL10, ultimately eliciting the inflammatory infiltration of macrophage. PMID- 26873849 TI - Effects of DDIT4 in Methamphetamine-Induced Autophagy and Apoptosis in Dopaminergic Neurons. AB - Methamphetamine (METH) is an illicit psychoactive drug that can cause a variety of detrimental effects to the nervous system, especially dopaminergic pathways. We hypothesized that DNA damage-inducible transcript 4 (DDIT4) is involved in METH-induced dopaminergic neuronal autophagy and apoptosis. To test the hypothesis, we determined changes of DDIT4 protein expression and the level of autophagy in rat catecholaminergic PC12 cells and human dopaminergic SH-SY5Y cells, and in the hippocampus, prefrontal cortex, and striatum of Sprague Dawley rats exposed to METH. We also examined the effects of silencing DDIT4 expression on METH-induced dopaminergic neuronal autophagy using fluorescence microscopy and electron microscopy. Flow cytometry and Western blot were used to determine apoptosis and the expression of apoptotic markers (cleaved caspase-3 and cleaved PARP) after blocking DDIT4 expression in PC12 cells and SH-SY5Y cells with synthetic siRNA, as well as in the striatum of rats by injecting LV-shDDIT4 lentivirus using a stereotaxic positioning system. Our results showed that METH exposure increased DDIT4 expression that was accompanied with increased autophagy and apoptosis in PC12 cells (3 mM) and SH-SY5Y cells (2 mM), and in the hippocampus, prefrontal cortex, and striatum of rats. Inhibition of DDIT4 expression reduced METH-induced autophagy and apoptosis in vitro and in vivo. However, DDIT4-related effects were not observed at a low concentration of METH (1 MUM). These results suggest that DDIT4 plays an essential role in METH-induced dopaminergic neuronal autophagy and apoptosis at higher doses and may be a potential gene target for therapeutics in high-dose METH-induced neurotoxicity. PMID- 26873850 TI - Resveratrol Protects SAMP8 Brain Under Metabolic Stress: Focus on Mitochondrial Function and Wnt Pathway. AB - Metabolic stress induced by high-fat (HF) diet leads to cognitive dysfunction and aging, but the physiological mechanisms are not fully understood. Senescence accelerated prone mouse (SAMP8) models were conducted under metabolic stress conditions by feeding HF for 15 weeks, and the preventive effect of resveratrol was studied. This dietary strategy demonstrates cognitive impairment in SAMP8-HF and significant preventive effect by resveratrol-treated animals. Hippocampal changes in the proteins involved in mitochondrial dynamics optic atrophy-1 protein (OPA1) and mitofusin 2 (MFN2) comprised a differential feature found in SAMP8-HF that was prevented by resveratrol. Electronic microscopy showed a larger mitochondria in SAMP8-HF + resveratrol (SAMP8-HF + RV) than in SAMP8-HF, indicating increases in fusion processes in resveratrol-treated mice. According to the mitochondrial morphology, significant increases in the I-NDUFB8, II-SDNB, III-UQCRC2, and V-ATPase complexes, in addition to that of voltage-dependent anion channel 1 (VDAC1)/porin, were found in resveratrol-treated animals with regard to SAMP8-HF, reaching control-animal levels. Moreover, tumor necrosis factor alpha (TNF-alpha) and interleukin (IL-6) were increased after HF, and resveratrol prevents its increase. Moreover, we found that the HF diet affected the Wnt pathway, as demonstrated by beta-catenin inactivation and modification in the expression of several components of this pathway. Resveratrol induced strong activation of beta-catenin. The metabolic stress rendered in the cognitive and cellular pathways altered in SAMP8 focus on different targets in order to act on preventing cognitive impairment in neurodegeneration, and resveratrol can offer therapeutic possibilities for preventive strategies in aging or neurodegenerative conditions. PMID- 26873851 TI - DJ-1/PARK7, But Not Its L166P Mutant Linked to Autosomal Recessive Parkinsonism, Modulates the Transcriptional Activity of the Orphan Nuclear Receptor Nurr1 In Vitro and In Vivo. AB - Although mutations of DJ-1 have been linked to autosomal recessive Parkinsonism for years, its physiological function and the pathological mechanism of its mutants are not well understood. We report for the first time that exogenous application of DJ-1, but not its L166P mutant, enhances the nuclear translocation and the transcriptional activity of Nurr1, a transcription factor essential for dopaminergic neuron development and maturation, both in vitro and in vivo. Knockdown of DJ-1 attenuates Nurr1 activity. Further investigation showed that signaling of Raf/MEK/ERK MAPKs is involved in this regulatory process and that activation induced by exogenous DJ-1 is antagonized by U0126, an ERK pathway inhibitor, indicating that DJ-1 modulates Nurr1 activity via the Raf/MEK/ERK pathway. Our findings shed light on the novel function of DJ-1 to enhance Nurr1 activity and provide the first insight into the molecular mechanism by which DJ-1 enhances Nurr1 activity. PMID- 26873852 TI - Elevated Serum and Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Unfavorable Functional Outcome in Subjects with Acute Ischemic Stroke. AB - The aim of this study was to evaluate the prognostic value of serum and cerebrospinal fluid (CSF) free fatty acid (FFA) levels in a cohort of patients with an acute ischemic stroke (AIS). In a prospective study, FFA levels were measured using an enzyme cycling method on admission in serum and CSF of 252 consecutive patients with AIS. The prognostic value of FFA to predict the functional outcome and mortality within 90-day was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Serum and CSF levels of FFA increased with increasing severity of stroke as defined by the NIHSS score (all P < 0.001). Patients with an unfavorable outcomes and non-survivors had significantly increased FFA serum and CSF levels on admission (all P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that serum FFA >=0.71 mmol/L (third quarters) was an independent predictor of functional outcome (odds ratios (OR) = 4.86; 95 % confidence interval (CI) 2.26-10.48) and mortality (OR = 7.72; 95 % CI 3.01 21.48). The area under the receiver operating characteristic curve of serum FFA was 0.79 (95 % CI, 0.72-0.86) for functional outcome and 0.86 (95 % CI, 0.78 0.94) for mortality. Similarly, CSF FFA level also was an indicator for predicting of functional outcome and mortality. FFA levels in serum and CSF may serve as independent biomarkers in addition of the traditional methods for assessing the functional outcome and mortality of AIS. PMID- 26873853 TI - Lentiviral-Mediated Netrin-1 Overexpression Improves Motor and Sensory Functions in SCT Rats Associated with SYP and GAP-43 Expressions. AB - Spinal cord injury (SCI), as a major cause of disability, usually causes serious loss of motor and sensory functions. As a bifunctional axonal guidance cue, netrin-1 can attract axons via the deleted in colorectal cancer (DCC) receptors and repelling others via Unc5 receptors, but its exact role in the recovery of motor and sensory function has not well been studied, and the mechanisms remains elusive. The aim of this experiment is to determine whether lentiviral (LV) mediated overexpression of netrin-1 or RNA interference (RNAi) can regulate the functional recovery in rats subjected to spinal cord transection (SCT). Firstly, two lentiviral vectors including Lv-exNtn-1 (netrin-1 open reading frame (ORF)) and Lv-shNtn-1 (netrin-1 sh) were constructed and injected into spinal cords rostral and caudal to the transected lesion site. Overexpressing netrin-1 enhanced significantly locomotor function, and reduced thermal and mechanical stimuli in vivo, compared with the control, while silencing netrin-1 did not significantly change the situation. Western blot and immunostaining analysis confirmed that netrin-1 ORF treatment not only effectively increased the expression level of netrin-1, also up-regulated the level of synaptophysin (SYP) in spinal cord rostral to the lesion, but also enhanced growth-associated protein 43 (GAP-43) expression in spinal cord caudal to the lesion site. Comparatively, knockdown of netrin-1 did not give rise to positive findings in our experimental condition. These findings therefore pointed that Lv-mediated netrin-1 overexpression could promote motor and sensory functional recoveries following SCT, and the underlying mechanisms were associated with SYP and GAP-43 expressions. The present study therefore provided a novel strategy for the treatment of SCI and explained the possible mechanisms for the functional improvement. PMID- 26873854 TI - Neuronal Activity-Induced Sterol Regulatory Element Binding Protein-1 (SREBP1) is Disrupted in Dysbindin-Null Mice-Potential Link to Cognitive Impairment in Schizophrenia. AB - Schizophrenia is a chronic debilitating neuropsychiatric disorder that affects about 1 % of the population. Dystrobrevin-binding protein 1 (DTNBP1 or dysbindin) is one of the Research Domain Constructs (RDoC) associated with cognition and is significantly reduced in the brain of schizophrenia patients. To further understand the molecular underpinnings of pathogenesis of schizophrenia, we have performed microarray analyses of the hippocampi from dysbindin knockout mice, and found that genes involved in the lipogenic pathway are suppressed. Moreover, we discovered that maturation of a master transcriptional regulator for lipid synthesis, sterol regulatory element binding protein-1 (SREBP1) is induced by neuronal activity, and is required for induction of the immediate early gene ARC (activity-regulated cytoskeleton-associated protein), necessary for synaptic plasticity and memory. We found that nuclear SREBP1 is dramatically reduced in dysbindin-1 knockout mice and postmortem brain tissues from human patients with schizophrenia. Furthermore, activity-dependent maturation of SREBP1 as well as ARC expression were attenuated in dysbindin-1 knockout mice, and these deficits were restored by an atypical antipsychotic drug, clozapine. Together, results indicate an important role of dysbindin-1 in neuronal activity induced SREBP1 and ARC, which could be related to cognitive deficits in schizophrenia. PMID- 26873855 TI - Activating Autophagy in Hippocampal Cells Alleviates the Morphine-Induced Memory Impairment. AB - Morphine abuse in treating severe and chronic pain has become a worldwide problem. But, chronic morphine exposure can cause memory impairment with its mechanisms not fully elucidated by past research sstudies which all focused on the harmful effects of morphine. Autophagy is an important pathway for cells to maintain survival. Here we showed that repeated morphine injection into C57BL/6 mice at a dose of 15 mg/kg per day for 7 days activated autophagic flux mainly in the hippocampi, especially in neurons of hippocampal CA1 region and microglia, with spatial memory impairment confirmed by Morris water maze test. Autophagy inhibition by 3-methyladenine obviously aggravates this morphine-induced memory impairment, accompanied with increased cell deaths in stratum pyramidale of hippocampal CA1, CA3, and DG regions and the activation of microglia to induce inflammation in hippocampus, such as upregulated expression of TNF-alpha, IL 1beta, IL-6, and iNOS, as well as NF-kappaB' s activation, while morphine alone promoted microglial immunosuppression in hippocampus with autophagy activation which was also confirmed in primary microglia. Taken together, our data indicates that autophagy activating in hippocampal cells can alleviate the memory impairment caused by morphine, by decreasing neuronal deaths in hippocampus and suppressing inflammation in hippocampal microglia, implying that modulating the activation of autophagy might be a promising method to prevent or treat the memory impairment caused by morphine. PMID- 26873856 TI - SORL1 Is Associated with the Risk of Late-Onset Alzheimer's Disease: a Replication Study and Meta-Analyses. AB - The sorting-related receptor gene (SORL1) has been defined as an interesting candidate gene for Alzheimer's disease (AD). Recently, one novel variant, rs11218343, within SORL1 was reported to be related to late-onset Alzheimer's disease (LOAD) in Caucasians, Korean, and Japanese. The aim of this case-control study is to investigate whether SORL1 rs11218343 contributes to susceptibility for LOAD in Chinese. Furthermore, our data, along with previously studies, were pooled for determining the risk of the rs11218343 polymorphism on LOAD. The rs11218343 polymorphism was genotyped in the 2350 independent subjects from Northern Han Chinese population (including 992 cases and 1358 age- and gender matched controls). Result of the case-control study showed the association between rs11218343 polymorphism and the risk of LOAD in a Northern Han Chinese population (recessive model: odds ratio (OR) = 0.641, 95 % confidence interval (CI) = 0.464-0.884, P = 0.007; additive model: OR = 0.873, 95 % CI = 0.765-0.996, P = 0.043). The results of meta-analysis in subgroups (Caucasian and Asian) and the whole showed that the minor allele (C allele) within rs11218343 played a protective effect on AD risk (OR (95 % CI), 0.77 (0.72-0.83), 0.85 (0.79-0.91), 0.81 (0.76-0.85), respectively). In conclusion, the C allele in SORL1 rs11218343 may be a protective factor for LOAD in both Caucasian and Han Chinese. PMID- 26873858 TI - Molecular Basis of Ligand Dissociation from the Adenosine A2A Receptor. AB - How drugs dissociate from their targets is largely unknown. We investigated the molecular basis of this process in the adenosine A2Areceptor (A2AR), a prototypical G protein-coupled receptor (GPCR). Through kinetic radioligand binding experiments, we characterized mutant receptors selected based on molecular dynamic simulations of the antagonist ZM241385 dissociating from the A2AR. We discovered mutations that dramatically altered the ligand's dissociation rate despite only marginally influencing its binding affinity, demonstrating that even receptor features with little contribution to affinity may prove critical to the dissociation process. Our results also suggest that ZM241385 follows a multistep dissociation pathway, consecutively interacting with distinct receptor regions, a mechanism that may also be common to many other GPCRs. PMID- 26873857 TI - Distinct Phosphorylation Clusters Determine the Signaling Outcome of Free Fatty Acid Receptor 4/G Protein-Coupled Receptor 120. AB - It is established that long-chain free fatty acids includingomega-3 fatty acids mediate an array of biologic responses through members of the free fatty acid (FFA) receptor family, which includes FFA4. However, the signaling mechanisms and modes of regulation of this receptor class remain unclear. Here, we employed mass spectrometry to determine that phosphorylation of mouse (m)FFAR4 occurs at five serine and threonine residues clustered in two separable regions of the C terminal tail, designated cluster 1 (Thr(347), Thr(349), and Ser(350)) and cluster 2 (Ser(357)and Ser(361)). Mutation of these phosphoacceptor sites to alanine completely prevented phosphorylation of mFFA4 but did not limit receptor coupling to extracellular signal regulated protein kinase 1 and 2 (ERK1/2) activation. Rather, an inhibitor of Gq/11proteins completely prevented receptor signaling to ERK1/2. By contrast, the recruitment of arrestin 3, receptor internalization, and activation of Akt were regulated by mFFA4 phosphorylation. The analysis of mFFA4 phosphorylation-dependent signaling was extended further by selective mutations of the phosphoacceptor sites. Mutations within cluster 2 did not affect agonist activation of Akt but instead significantly compromised receptor internalization and arrestin 3 recruitment. Distinctly, mutation of the phosphoacceptor sites within cluster 1 had no effect on receptor internalization and had a less extensive effect on arrestin 3 recruitment but significantly uncoupled the receptor from Akt activation. These unique observations define differential effects on signaling mediated by phosphorylation at distinct locations. This hallmark feature supports the possibility that the signaling outcome of mFFA4 activation can be determined by the pattern of phosphorylation (phosphorylation barcode) at the C terminus of the receptor. PMID- 26873859 TI - Barriers and facilitators to the nationwide dissemination of the Dutch school based obesity prevention programme DOiT. AB - BACKGROUND: This article describes the barriers and facilitating factors to the adoption, implementation and continuation of the Dutch Obesity Intervention in Teenagers (DOiT) programme in the Netherlands. METHODS: We evaluated the adoption, implementation and continuation of the programme at 20 voluntary prevocational schools, which adopted the programme. Interviews were conducted with DOiT coordinators and/or teachers (n = 44) at the end of the first and second school year of the 2-year implementation period. Interviews were recorded and transcribed verbatim. Data were coded by two researchers independently. Identified barriers and facilitating factors were categorized into four groups: (i) organizational factors, (ii) individual factors, (iii) characteristics of the programme and (iv) characteristics of the implementation strategy. RESULTS: Teachers and DOiT coordinators identified various implementation barriers (e.g. lack of planning, other urgent unforeseen priorities, no plan to cope with teacher turnover and high teacher workload) as well as facilitating factors (e.g. involvement of DOiT coordinator and support from the DOiT office, sufficient communication and collaboration between teachers, strong teacher motivation and flexibility of the programme). CONCLUSION: Overall, DOiT implementers were satisfied with the compatibility, layout, content and potential for tailoring the programme. Barriers for successful implementation were mainly at the school and teacher level. Findings of this study can be used for further improvement of the DOiT programme and for the development and improvement of other health promotion programmes in the school setting. PMID- 26873860 TI - The impact of a school food aid program on household food insecurity. AB - BACKGROUND: We had a unique opportunity to establish the extent of food insecurity and the potential impact of a large-scale school-based nutritional program, in low-socioeconomic status districts of Greece, during the current economic crisis. METHODS: Around 162 schools with 25 349 students participated during the 2012-2013 school year. Each student received a daily healthy meal designed by nutrition specialists. Food insecurity levels, measured using the Food Security Survey Module were assessed at baseline and after a 1-8-month intervention period. Pre-post intervention responses were matched at an individual level. RESULTS: Around 64.2% of children's households experienced food insecurity at baseline. This percentage decreased to 59.1% post-intervention,P< 0.001. On an individual level, food insecurity score diminished by 6.5%,P< 0.001. After adjustment for various socioeconomic factors, for each additional month of participation, the odds of reducing the food insecurity score increased by 6.3% (OR = 1.06, 95% CI: 1.02-1.11). Those experiencing food insecurity with hunger at baseline were more likely to improve food insecurity score than those who did not (OR = 3.51, 95%CI: 2.92-4.21). CONCLUSION: Children and families residing in low socioeconomic areas of Greece, experience high levels of food insecurity. Our findings suggest that participation in a school-based food aid program may reduce food insecurity for children and their families in a developed country in times of economic hardship. PMID- 26873861 TI - Healthy human second-trimester fetal skin is deficient in leukocytes and associated homing chemokines. AB - The lack of immune cells in mid-gestational fetal skin is often mentioned as a key factor underlying scarless healing. However, the scarless healing ability is conserved until long after the immune system in the fetus is fully developed. Therefore, we studied human second-trimester fetal skin and compared the numbers of immune cells and chemokine levels from fetal skin with adult skin. By using immunohistochemistry, we show that healthy fetal skin contains significant lower numbers of CD68(+) -macrophages, Tryptase(+) -mast cells, Langerin(+) -Langerhans cells, CD1a(+) -dendritic cells, and CD3(+) -T cells compared to adult skin. Staining with an early lineage leukocyte marker, i.e., CD45, verified that the number of CD45(+) -immune cells was indeed significantly lower in fetal skin but that sufficient numbers of immune cells were present in the fetal lymph node. No differences in the vascular network were observed between fetal and adult skin. Moreover, significant lower levels of lymphocyte chemokines CCL17, CCL21, and CCL27 were observed in fetal skin. However, levels of inflammatory interleukins such as IL-6, IL-8, and IL-10 were undetectable and levels of CCL2 were similar in healthy fetal and adult skin. In conclusion, this study shows that second trimester fetal skin contains low levels of immune cells and leukocyte chemokines compared to adult skin. This immune cell deficiency includes CD45(+) leukocytes, despite the abundant presence of these cells in the lymph node. The immune deficiency in healthy second-trimester fetal skin may result in reduced inflammation during wound healing, and could underlie the scarless healing capacities of the fetal skin. PMID- 26873862 TI - A New In Vitro Co-Culture Model Using Magnetic Force-Based Nanotechnology. AB - Skeletal myoblast (SkMB) transplantation has been conducted as a therapeutic strategy for severe heart failure. However, arrhythmogenicity following transplantation remains unsolved. We developed an in vitro model of myoblast transplantation with "patterned" or "randomly-mixed" co-culture of SkMBs and cardiomyocytes enabling subsequent electrophysiological, and arrhythmogenic evaluation. SkMBs were magnetically labeled with magnetite nanoparticles and co cultured with neonatal rat ventricular myocytes (NRVMs) on multi-electrode arrays. SkMBs were patterned by a magnet beneath the arrays. Excitation synchronicity was evaluated by Ca(2+) imaging using a gene-encoded Ca(2+) indicator, G-CaMP2. In the monoculture of NRVMs (control), conduction was well organized. In the randomly-mixed co-culture of NRVMs and SkMBs (random group), there was inhomogeneous conduction from multiple origins. In the "patterned" co culture where an en bloc SKMB-layer was inserted into the NRVM-layer, excitation homogenously propagated although conduction was distorted by the SkMB-area. The 4 mm distance conduction time (CT) in the random group was significantly longer (197 +/- 126 ms) than in control (17 +/- 3 ms). In the patterned group, CT through NRVM-area did not change (25 +/- 3 ms), although CT through the SkMB-area was significantly longer (132 +/- 77 ms). The intervals between spontaneous excitation varied beat-to-beat in the random group, while regular beating was recorded in the control and patterned groups. Synchronized Ca(2+) transients of NRVMs were observed in the patterned group, whereas those in the random group were asynchronous. Patterned alignment of SkMBs is feasible with magnetic nanoparticles. Using the novel in vitro model mimicking cell transplantation, it may become possible to predict arrhythmogenicity due to heterogenous cell transplantation. J. Cell. Physiol. 231: 2249-2256, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26873864 TI - Chemotherapy in ovarian germ cell tumors: A systematic review. AB - OBJECTIVE: Ovarian germ cell tumors (OGCTs) are rare tumors that comprise a diverse group of histologic subtypes that can either be benign or malignant. Malignant ovarian germ cell tumors (OGCTs) historically carried a poor prognosis, especially among those diagnosed with advanced disease. With the advent of combination chemotherapy, risk of relapse has markedly decreased. There is limited prospective data on the efficacy of specific chemotherapy regimens in the treatment of malignant OGCTs. This article critically reviews the literature pertinent to the treatment of OGCTs with chemotherapy. METHODS: MEDLINE was searched for English language literature on prospective studies on the treatment of malignant OGCTs, focusing on publications since 1995. RESULTS: As modern chemotherapy regimens have evolved, risk of relapse has decreased with implementation of platinum based regimens in the adjuvant setting. However, the role of neoadjuvant platinum based regimens and treatment of metastatic or recurrent malignant OGCTs remains poorly understood due to lack of randomized control trials. CONCLUSIONS: Malignant OGCTs represent a rare subset of ovarian neoplasms for which focused, prospective clinical trials are needed to determine the most effective therapies. PMID- 26873863 TI - The effects of arginine glutamate, a promising excipient for protein formulation, on cell viability: Comparisons with NaCl. AB - The effects of an equimolar mixture of l-arginine and l-glutamate (Arg.Glu) on cell viability and cellular stress using in vitro cell culture systems are examined with reference to NaCl, in the context of monoclonal antibody formulation. Cells relevant to subcutaneous administration were selected: the human monocyte cell line THP-1, grown as a single cell suspension, and adherent human primary fibroblasts. For THP-1 cells, the mechanism of cell death caused by relatively high salt concentrations was investigated and effects on cell activation/stress assessed as a function of changes in membrane marker and cytokine (interleukin-8) expression. These studies demonstrated that Arg.Glu does not have any further detrimental effects on THP-1 viability in comparison to NaCl at equivalent osmolalities, and that both salts at higher concentrations cause cell death by apoptosis; there was no significant effect on measures of THP-1 cellular stress/activation. For adherent fibroblasts, both salts caused significant toxicity at ~400 mOsm/kg, although Arg.Glu caused a more precipitous subsequent decline in viability than did NaCl. These data indicate that Arg.Glu is of equivalent toxicity to NaCl and that the mechanism of toxicity is such that cell death is unlikely to trigger inflammation upon subcutaneous injection in vivo. PMID- 26873865 TI - Natural history and outcome of neuroendocrine carcinoma of the cervix. AB - OBJECTIVE: Neuroendocrine carcinomas of the cervix (NECC) are rare and thought to be aggressive. We performed a population-based analysis to examine the natural history, treatment patterns and outcomes of women with NECC compared to squamous cell carcinoma (SCCC) and adenocarcinoma (AC) of the cervix. METHODS: The National Cancer Database (NCDB) was utilized to identify women with NECC, SCCC, and AC treated from 1998 to 2011. Clinical, demographic, and treatment characteristics were compared between the groups. The association between tumor histology and survival was examined using Kaplan-Meier analyses and multivariable Cox proportional hazards regression models. RESULTS: We identified 127,332 patients, including 1,896 (1.5%) with NECC and 101,240 (79.5%) with SCCC and 24,196 (19.0%) with AC. Patients with NECC were younger, more often white, commercially insured, and diagnosed with metastatic disease at presentation compared to women with SCCC. Patients with early-stage NECC were more likely to receive adjuvant chemotherapy and radiation after surgery (P<0.05 for both). In multivariable models stratified by stage and adjusted for clinical and demographic characteristics, the risk of death was higher for patients with NECC compared to SCCC for all stages of disease: stages IB-IIA (HR=2.96; 95% CI, 2.48 3.52), stages IIB-IVA (HR=1.70; 95% CI, 1.45-1.99) and stage IVB (HR=1.14; 95% CI, 0.91-1.43). CONCLUSION: NECC are aggressive tumors associated with an increased risk of death. Survival is inferior for NECC compared to squamous cell tumors for women with both early and advanced stage disease. PMID- 26873866 TI - MicroRNA-183 functions as the tumor suppressor via inhibiting cellular invasion and metastasis by targeting MMP-9 in cervical cancer. AB - OBJECTIVE: MicroRNAs have been reported to play an important role in the invasion and metastasis of cervical cancer. miR-183 was found to inhibit or promote the invasion and metastasis of multiple solid tumors. However, the roles of miR-183 in cervical cancer are unclear. METHODS: In this study, miR-183 expression levels were measured in 53 cervical cancer and 13 normal cervical tissues by qRT-PCR. The effects of forced expression of miR-183 on cervical cancer cells invasion and metastasis were investigated using Transwell uncoated or coated with growth factor-reduced Matrigel for migration or invasion assays, respectively. RESULTS: We found that miR-183 expression levels were significantly down-regulated in cervical cancer tissues compared with normal tissues (0.15+/-0.011 to 0.86+/ 0.049). Ectopic expression of miR-183 resulted in the suppression of invasion and migration of cervical cancer cell lines, siha and Hela cells (p<0.0001). Bioinformatics analysis revealed that MMP-9 was the potential target of miR-183 and it was found that MMP-9 was remarkably up-regulated in cervical cancer. Furthermore, a dual-luciferase reporter assay showed that MMP-9 as a target of miR-183 (p<0.0001). The invasion and metastasis ability of siha and Hela was suppressed when MMP-9 was down-regulated in vitro (p<0.0001). CONCLUSIONS: In conclusion, our study revealed that miR-183 might be a tumor suppressor via inhibiting the invasion and metastasis of cervical cancer cells through targeting MMP-9, indicating that miR-183 may be a novel potential therapeutic target for cervical cancer. PMID- 26873867 TI - Development of core outcome sets in hidradenitis suppurativa: systematic review of outcome measure instruments to inform the process. AB - The recent hidradenitis suppurativa (HS) Cochrane review identified outcome measure heterogeneity as an important issue to address when designing future HS trials. Our objective was to follow the Harmonising Outcome Measures for Eczema (HOME) roadmap, by performing a systematic review of HS outcome measure instruments to inform the development of an HS core outcome set. We performed a systematic review to identify validation evidence for outcome measure instruments used in HS randomized controlled trials (RCTs), and assessed the methodological quality of all HS outcome measure validity studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The 12 RCTs included in the Cochrane review utilized 30 outcome measure instruments, including 16 physician-reported instruments, 11 patient-reported instruments and three composite measures containing elements of both. Twenty seven (90%) of the instruments lacked any validation data. Two further instruments have been developed and partially validated. Of the seven studies meeting our inclusion criteria, six were of 'fair' or 'poor' methodological quality, in part because most of the studies were not primarily designed for instrument validation. The HiSCR instrument is supported by good-quality validation data, but there are gaps, including assessment of internal consistency, inter-rater reliability and minimal clinically important difference, and convergent validity fell below the acceptable range for some comparisons. Multiple, usually unvalidated, outcome measure instruments have been used in HS RCTs. Where validation evidence is available there are issues of low methodological quality or incomplete validity assessment and so, currently, no instruments can be fully recommended. PMID- 26873869 TI - Correction. PMID- 26873870 TI - Lichen planus and dyslipidemia: a systematic review and meta-analysis of observational studies. AB - BACKGROUND: Lichen planus (LP) is a chronic inflammatory disease that has been shown to be positively associated with dyslipidemia. However, the magnitude and types of the underlying lipid abnormalities have not been investigated. This study aims to conduct a systematic review and meta-analysis to investigate the qualitative and quantitative association between LP and dyslipidemia. METHODS: A systematic search of studies published from inception to April 1, 2015, was conducted using MEDLINE, EMBASE, Web of Science, and Cochrane library databases. Meta-analyses of observational studies with both categorical and continuous outcome were performed. DerSimonian and Lard random effects models were utilized to calculate the pooled odds ratio and weighted mean difference (WMD). Publication bias was evaluated by funnel plot and Egger's test. RESULTS: Seven studies with 5242 subjects were included in this meta-analysis. Patients with LP were significantly more likely to have dyslipidemia, with a pooled odds ratio of 1.74 (95% confidence interval [CI]: 1.19-2.54, P = 0.004). LP was associated with higher levels of triglycerides (WMD 83.37 mg/dl, 95% CI 0.62-166.12, P = 0.048), low-density lipoprotein (18.75 mg/dl, 95% CI -17.21 to 54.72, P = 0.307), total cholesterol (19.22 mg/dl, 95% CI -8.80 to 47.25, P = 0.179), and lower levels of high-density lipoprotein cholesterol (-8.96 mg/dl, 95% CI -21.22 to 3.30, P = 0.152). CONCLUSIONS: Despite considerable heterogeneity, this study demonstrated that LP was significantly associated with an increased risk of dyslipidemia and higher triglyceride levels. For patients presenting with LP, physicians should be cognizant of this association and consider screening them for dyslipidemia. PMID- 26873871 TI - Gender-related different effects of a combined therapy of Exenatide and Metformin on overweight or obesity patients with type 2 diabetes mellitus. AB - BACKGROUND: Although men and women have similar diabetes prevalence, the same medicine will cause different therapeutic results in different genders. To understand the molecular mechanism, we explored the effects of a combined therapy of Exenatide and Metformin on obesity and overweight female and male patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: One hundred and five overweight and obesity patients with newly diagnosed T2DM (n=54 female in a female group and n=51 males in a male group) received the therapy: 5 MUg Exenatide+0.5 g MET twice daily for 4 weeks, then 10 MUg Exenatide+0.5 g MET twice daily for 24 weeks. RESULTS: There was an average of 8.2 +/- 2.4 kg and 4.6 +/- 2.3 kg weight loss in female and male patients, respectively. The combined therapy showed better effects on female than male patients for improving insulin sensitivity and serum lipid profile, reducing insulin resistance, increasing adiponectin levels, and decreasing the levels of HbA1c, BMI, resistin, TNF-alpha and C-reactive protein (P<0.05). CONCLUSIONS: The combined therapy of Exenatide and MET shows better therapeutic results in female patients than in male patients. Therefore, the dual therapy is more suitable for female patients. PMID- 26873868 TI - Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. AB - The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 RECEPTOR ANTAGONISTS CLOPIDOGREL, PRASUGREL, TICAGRELOR: For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). WARFARIN: The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. DIRECT ORAL ANTICOAGULANTS DOAC: For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken >=48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30-50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID- 26873872 TI - Coupling of the non-amyloid-component (NAC) domain and the KTK(E/Q)GV repeats stabilize the alpha-synuclein fibrils. AB - The aggregates of alpha-synuclein (alphaS) are a major pathological hallmark of Parkinson's disease (PD) making their structure-function relationship important for rational drug design. Yet, the atomic structure of the alphaS aggregates is unavailable, making it difficult to understand the underlying aggregation mechanism. In this work, based on available experimental data, we examined plausible molecular structures of alphaS(20/30-110) fibrils for the first time by employing computational approaches. The optimized structure was used to investigate possible interactions with aggregation inhibitors. Our structural models characterize the essential properties of the five-layered fold of the alphaS fibril. The distribution of the beta-strands and the topology of the five beta-strands in the relatively stable models are in good agreement with experimental values. In particular, we find that the KTK(E/Q)GV repeat motifs significantly stabilize the alphaS fibrils. The charged residues within each repeat prefer exposure to the solvent in order to further stabilize the inter layered interactions by salt-bridges. The organization of the repeat K(58)T(59)K(60)E(61)Q(62)V(63) between the beta2 and beta3 layers significantly affects the stability of the non-amyloid-component (NAC) domain. The coupling between the NAC domain and the KTKEGV repeats indicates that both regions can be potential binding sites for inhibitor design. The distinct binding modes of chemical agents that alter alphaS aggregation highlight the potential of our models in inhibitor design. PMID- 26873873 TI - Community walking speed, sedentary or lying down time, and mortality in peripheral artery disease. AB - We studied whether slower community walking speed and whether greater time spent lying down or sleeping were associated with higher mortality in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 0.90 were identified from Chicago medical centers. At baseline, participants reported their usual walking speed outside their home and the number of hours they spent lying down or sleeping per day. Cause of death was adjudicated using death certificates and medical record review. Analyses were adjusted for age, sex, race, comorbidities, ABI, and other confounders. Of 1314 PAD participants, 189 (14.4%) died, including 63 cardiovascular disease (CVD) deaths. Mean follow-up was 34.9 months +/- 18.1. Relative to average or normal pace (2-3 miles/hour), slower walking speed was associated with greater CVD mortality: no walking at all: hazard ratio (HR) = 4.17, 95% confidence interval (CI) = 1.46-11.89; casual strolling (0-2 miles/hour): HR = 2.24, 95% CI = 1.16 4.32; brisk or striding (>3 miles/hour): HR = 0.55, 95% CI = 0.07-4.30. These associations were not significant after additional adjustment for the six-minute walk. Relative to sleeping or lying down for 8-9 hours, fewer or greater hours sleeping or lying down were associated with higher CVD mortality: 4-7 hours: HR = 2.08, 95% CI = 1.06-4.05; 10-11 hours: HR = 4.07, 95% CI = 1.86-8.89; ? 12 hours: HR = 3.75, 95% CI = 1.47-9.62. These associations were maintained after adjustment for the six-minute walk. In conclusion, slower walking speed outside the home and less than 8 hours or more than 9 hours lying down per day are potentially modifiable behaviors associated with increased CVD mortality in patients with PAD. PMID- 26873874 TI - Identification of the MmeHairy gene and expression analysis affected by two SNPs in the 3'-untranslated region in the clam Meretrix meretrix. AB - As a bHLH transcriptional repressor, Hairy-related proteins can bind to DNA sites in target gene promoters and negatively regulate gene transcription. In the present study, the full-length cDNA of Hairy was obtained from the clam Meretrix meretrix (MmeHairy), and two SNPs in the 3'-untranslated region (UTR) of this gene, SNP1066 and 1067, were identified and characterized. Multiple sequence alignment and phylogenetic analysis revealed that MmeHairy belongs to the Hairy protein subfamily. Analysis of tissue expression patterns showed that the mRNA of MmeHairy had the highest expression level in the hepatopancreas. The expression levels of MmeHairy were up-regulated in the hepatopancreas after Vibrio challenge. Genotyping and quantitative analysis showed that the mRNA levels of MmeHairy were significantly different among individual clams with different genotypes at SNP1066 and 1067 (P < 0.05), which indicated that these two SNP loci may affect the expression of MmeHairy and could be used as candidate markers for future selection in M. meretrix breeding programs. PMID- 26873876 TI - The private, online GP will see you now. PMID- 26873875 TI - Immunolocalization of immune cells and cell cycle proteins in the bulbus arteriosus of Atlantic salmon (Salmo salar L.). AB - The bulbus arteriosus is the most anterior chamber of the teleost heart. The present study aimed to establish the presence, and to provide semi-quantitative information on the abundance, of several immune and cell-cycle proteins in the bulbus arteriosus of healthy Atlantic salmon (Salmo salar L.). Using immunohistochemistry, lymphocyte-like cells were identified in the bulbus arteriosus using antibodies to CD3epsilon and MHC class IIbeta. Few PCNA positive cells were identified in post-smolt fish as compared to moderate levels of staining in fresh water fry. Interestingly no staining was evident in adult fish (1-3 kg), thus there was a loss of cells expressing cell-cycle regulatory proteins with ontogeny/progressive life-history stages. Eosinophilic granulocytes (EGCs) were identified in the bulbus arteriosus using TNFalpha and HIF1alpha antibodies. Anti-caspase 3 immune-reaction identified a strong endothelial cytoplasmic staining in the bulbus arteriosus. Taken together, the immunolocalization of immune-related molecules (CD3, MHC class II and TNFalpha), cell-cycle regulatory proteins (PCNA and HIF1alpha) and apoptosis markers (TUNEL, caspase 3) suggest that the bulbus arteriosus may have an immune component within its functional repertoire. PMID- 26873878 TI - Proteome analysis of Bordetella pertussis isolated from human macrophages. AB - Previous studies have shown that B. pertussis survives inside human macrophages in non-acidic compartments with characteristics of early endosomes. In order to gain new insight into the biology of B. pertussis survival in host cells, we have analyzed the adaptation of the bacterial proteome during intracellular infection. The proteome of B. pertussis 3 h and 48 h after infection of human macrophage like THP-1 cells was examined by nano-liquid chromatography combined with tandem MS and compared to the protein profile of extracellular B. pertussis growing in the same cell culture medium. Compared with extracellular bacteria, almost 300 proteins out of 762 identified proteins displayed altered levels in intracellular B. pertussis. Functional analyses of the proteins displaying altered abundance revealed enrichment of proteins involved in stress response, iron uptake, cellular metabolism, transcriptional regulation, and virulence. To our knowledge, this is the first analysis of the B. pertussis proteome during adaptation to the intramacrophage environment and the data provide new clues for understanding B. pertussis adaptation and pathogenesis. BIOLOGICAL SIGNIFICANCE: B. pertussis is a respiratory pathogen that has adapted exclusively to the human host. Despite high vaccination rates, whooping cough remains a serious threat to human health and its incidence has been increasing in recent years in vaccinated populations. The mechanisms that allow this pathogen to evade immune clearance, persist in the host, and cause a prolonged paroxysmal cough are still poorly understood. Recent studies regarding B. pertussis survival inside host cells and the cellular response to this bacterial infection indicate that B. pertussis may have an intracellular phase during infection which probably contributes to persistence and vaccine failure. In this study we provide the first global proteome profile of B. pertussis within macrophages. The data provide novel insights into the adaptive responses elicited by these bacteria for physiological adaptation to the host environment. PMID- 26873877 TI - Rac1 regulates bacterial toxin-induced thrombin generation. AB - OBJECTIVE: Systemic inflammatory response syndrome is associated with severe coagulopathy. The purpose of this study was to examine thrombin generation in systemic inflammation triggered by the endotoxin lipopolysaccharide (LPS) and the exotoxin streptococcal M1 protein. METHODS: Thrombin generation, lung histology and myeloperoxidase (MPO) activity were determined 6 and 24 h after induction of systemic inflammation. Male C57BL/6 mice received the Rac1 inhibitor NSC23766 prior to challenge with bacterial toxins. RESULTS: LPS and M1 protein challenge increased neutrophil infiltration and caused damage in the lung. Time to peak thrombin formation was increased and peak and total generation of thrombin were decreased in plasma from LPS- and M1 protein-treated mice. Coincubation of samples from mice exposed to bacterial toxins with platelet poor plasma from healthy mice completely reversed the inhibitory effect of LPS and M1 protein on thrombin generation, suggesting that bacterial toxins decreased levels of plasma factors explaining the reduction of thrombin generating capacity of plasma from septic animals. NSC23766 treatment not only decreased LPS- and M1 protein-induced neutrophil accumulation as well as levels of interleukin-6 and CXCL2 in the lung, but also abolished bacterial toxin-induced changes in thrombin generation. For example, NSC23766 increased peak formation by 57% and total thrombin generation by 48% in LPS-treated animals at 6 h. CONCLUSIONS: Taken together, our novel findings show that bacterial toxins increase thrombin generation via consumption of plasma factors and that Rac1 signaling plays an important role in thrombin generation in response to bacterial toxins. Thus, targeting Rac1 activity might be a useful way not only to ameliorate pulmonary inflammation, but also inhibit pathological changes in coagulation in bacterial infections. PMID- 26873879 TI - Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly. AB - Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. PMID- 26873880 TI - Detection of novel metabolites of flaxseed lignans in vitro and in vivo. AB - SCOPE: This study aimed to improve the knowledge of secoisolariciresinol diglucoside (SDG) transformation by human gut microbiota. METHODS AND RESULTS: SDG-supplemented microbiota cultures were inoculated with the feces of five subjects. The same volunteers received a flaxseed supplement for 7 days. SDG metabolites in cultures, feces, and urine were monitored by LC-ESI-QTOF and LC DAD. In all cultures, SDG was deglycosylated to secoisolariciresinol (SECO) within 12 h. SECO underwent successive dehydroxylations and demethylations yielding enterodiol (4-18% conversion) and enterolactone (0.2-6%) after 24 h. Novel intermediates related to SECO, matairesinol (MATA), and anhydrosecoisolariciresinol (AHS) were identified in fecal cultures. These metabolites were also found after flaxseed consumption in feces and urine (in approximate amounts between 0.01-47.03 MUg/g and 0.01-13.49 MUg/mL, respectively) in their native form and/or modified by phase II human enzymes (glucuronide, sulfate and sulfoglucuronide conjugates). CONCLUSIONS: Derivatives of MATA and AHS are described for the first time as intermediates of SDG biotransformation by intestinal bacteria, providing a more comprehensive knowledge of lignan intestinal metabolism. The transformations observed in vitro seem to occur in vivo as well. The detection in urine of SDG intermediates indicates their gut absorption, opening new perspectives on the study of their systemic biological effects. PMID- 26873882 TI - Function changing mutations in glucocorticoid receptor evolution correlate with their relevance to mode coupling. AB - Nonlinear effects in protein dynamics are expected to play role in function, particularly of allosteric nature, by facilitating energy transfer between vibrational modes. A recently proposed method focusing on the non-Gaussian shape of the configurational population near equilibrium projects this information onto real space in order to identify the aminoacids relevant to function. We here apply this method to three ancestral proteins in glucocorticoid receptor (GR) family and show that the mutations that restrict functional activity during GR evolution correlate significantly with locations that are highlighted by the nonlinear contribution to the near-native configurational distribution. Our findings demonstrate that the analysis of nonlinear effects in protein dynamics can be harnessed into a predictive tool for functional site determination. PMID- 26873881 TI - Charcot-marie-tooth disease type 1X in women: Electrodiagnostic findings. AB - INTRODUCTION: Symptoms and signs in women with Charcot-Marie-Tooth disease type 1X (CMT1X) are often milder from those in men, but the available electrophysiologic evidence regarding CMT1X in women has been characterized in some patients as non-uniform or asymmetric. METHODS: We retrospectively reviewed electrodiagnostic findings from 45 women and 31 men with CMT1X. RESULTS: Motor nerve conduction parameters in CMT1X women were less abnormal (P < 0.05), and a wider range of motor conduction velocities (CVs) were seen in women (P < 0.001) compared with men. In women, nerve conduction studies showed lack of conduction block without temporal dispersion. Motor CVs were more frequently in the normal range in women compared with men. There was no significant relationship to age of presentation and motor CV or compound muscle action potential in women. CONCLUSION: NCS parameters in CMT1X women did not demonstrate features suggestive of an acquired demyelinating neuropathy. Muscle Nerve, 2016 Muscle Nerve 54: -, 2016 Muscle Nerve 54: 728-732, 2016. PMID- 26873883 TI - Critical micelle concentration values for different surfactants measured with solid-phase microextraction fibers. AB - The amphiphilic nature of surfactants drives the formation of micelles at the critical micelle concentration (CMC). Solid-phase microextraction (SPME) fibers were used in the present study to measure CMC values of 12 nonionic, anionic, cationic, and zwitterionic surfactants. The SPME-derived CMC values were compared to values determined using a traditional surface tension method. At the CMC of a surfactant, a break in the relationship between the concentration in SPME fibers and the concentration in water is observed. The CMC values determined with SPME fibers deviated by less than a factor of 3 from values determined with a surface tension method for 7 out of 12 compounds. In addition, the fiber-water sorption isotherms gave information about the sorption mechanism to polyacrylate-coated SPME fibers. A limitation of the SPME method is that CMCs for very hydrophobic cationic surfactants cannot be determined when the cation exchange capacity of the SPME fibers is lower than the CMC value. The advantage of the SPME method over other methods is that CMC values of individual compounds in a mixture can be determined with this method. However, CMC values may be affected by the presence of compounds with other chain lengths in the mixture because of possible mixed micelle formation. Environ Toxicol Chem 2016;35:2173-2181. (c) 2016 SETAC. PMID- 26873885 TI - Perfusion information extracted from resting state functional magnetic resonance imaging. AB - It is widely known that blood oxygenation level dependent (BOLD) contrast in functional magnetic resonance imaging (fMRI) is an indirect measure for neuronal activations through neurovascular coupling. The BOLD signal is also influenced by many non-neuronal physiological fluctuations. In previous resting state (RS) fMRI studies, we have identified a moving systemic low frequency oscillation (sLFO) in BOLD signal and were able to track its passage through the brain. We hypothesized that this seemingly intrinsic signal moves with the blood, and therefore, its dynamic patterns represent cerebral blood flow. In this study, we tested this hypothesis by performing Dynamic Susceptibility Contrast (DSC) MRI scans (i.e. bolus tracking) following the RS scans on eight healthy subjects. The dynamic patterns of sLFO derived from RS data were compared with the bolus flow visually and quantitatively. We found that the flow of sLFO derived from RS fMRI does to a large extent represent the blood flow measured with DSC. The small differences, we hypothesize, are largely due to the difference between the methods in their sensitivity to different vessel types. We conclude that the flow of sLFO in RS visualized by our time delay method represents the blood flow in the capillaries and veins in the brain. PMID- 26873884 TI - Ultraviolet-A triggers photoaging in model nematode Caenorhabditis elegans in a DAF-16 dependent pathway. AB - Ultraviolet radiations (UV) are the primary causative agent for skin aging (photoaging) and cancer, especially UV-A. The mode of action and the molecular mechanism behind the damages caused by UV-A is not well studied, in vivo. The current study was employed to investigate the impact of UV-A exposure using the model organism, Caenorhabditis elegans. Analysis of lifespan, healthspan, and other cognitive behaviors were done which was supported by the molecular mechanism. UV-A exposure on collagen damages the synthesis and functioning which has been monitored kinetically using engineered strain, col-19:: GFP. The study results suggested that UV-A accelerated the aging process in an insulin-like signaling pathway dependent manner. Mutant (daf-2)-based analysis concrete the observations of the current study. The UV-A exposure affected the usual behavior of the worms like pharyngeal movements and brood size. Quantitative PCR profile of the candidate genes during UV-A exposure suggested that continuous exposure has damaged the neural network of the worms, but the mitochondrial signaling and dietary restriction pathway remain unaffected. Western blot analysis of HSF-1 evidenced the alteration in protein homeostasis in UV-A exposed worms. Outcome of the current study supports our view that C. elegans can be used as a model to study photoaging, and the mode of action of UV-A-mediated damages can be elucidated which will pave the way for drug developments against photoaging. PMID- 26873886 TI - Major remodeling of brain microvessels during neonatal period in the mouse: A proteomic and transcriptomic study. AB - Preterm infants born before 29 gestation weeks incur major risk of subependymal/intracerebral/intraventricular hemorrhage. In mice, neonate brain endothelial cells are more prone than adult cells to secrete proteases under glutamate challenge, and invalidation of the Serpine 1 gene is accompanied by high brain hemorrhage risk up to five days after birth. We hypothesized that the structural and functional states of microvessels might account for age-dependent vulnerability in mice up to five days after birth and might represent a pertinent paradigm to approach the hemorrhage risk window observed in extreme preterms. Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways. Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways. Both approaches pointed towards extracellular matrix, cell adhesion and junction pathways, indicating delayed microvascular strengthening after P5. Furthermore, glutamate receptors, proteases and their inhibitors exhibited convergent evolutions towards excitatory aminoacid sensitivity and low proteolytic control likely accounting for vascular vulnerability in P5 mice. Thus, age vascular specificities must be considered in future therapeutic interventions in preterms. Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870). PMID- 26873887 TI - Stimulation of astrocyte fatty acid oxidation by thyroid hormone is protective against ischemic stroke-induced damage. AB - We previously demonstrated that stimulation of astrocyte mitochondrial ATP production via P2Y1 receptor agonists was neuroprotective after cerebral ischemic stroke. Another mechanism that increases ATP production is fatty acid oxidation (FAO). We show that in primary human astrocytes, FAO and ATP production are stimulated by 3,3,5 triiodo-l-thyronine (T3). We tested whether T3-stimulated FAO enhances neuroprotection, and show that T3 increased astrocyte survival after either hydrogen peroxide exposure or oxygen glucose deprivation. T3-mediated ATP production and protection were both eliminated with etomoxir, an inhibitor of FAO. T3-mediated protection in vitro was also dependent on astrocytes expressing HADHA (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase), which we previously showed was critical for T3-mediated FAO in fibroblasts. Consistent with previous reports, T3-treatment decreased stroke volumes in mice. While T3 decreased stroke volume in etomoxir-treated mice, T3 had no protective effect on stroke volume in HADHA +/- mice or in mice unable to upregulate astrocyte-specific energy production. In vivo, 95% of HADHA co localize with glial-fibrillary acidic protein, suggesting the effect of HADHA is astrocyte mediated. These results suggest that astrocyte-FAO modulates lesion size and is required for T3-mediated neuroprotection post-stroke. To our knowledge, this is the first report of a neuroprotective role for FAO in the brain. PMID- 26873888 TI - Measurement of cerebral blood flow using phase contrast magnetic resonance imaging and duplex ultrasonography. AB - Phase contrast magnetic resonance imaging (PC-MRI) and color-coded duplex ultrasonography (CDUS) are commonly used for measuring cerebral blood flow in the internal carotid (ICA) and vertebral arteries. However, agreement between the two methods has been controversial. Recent development of high spatial and temporal resolution blood vessel wall edge-detection and wall-tracking methods with CDUS increased the accuracy and reliability of blood vessel diameter, hence cerebral blood flow measurement. The aim of this study was to compare the improved CDUS method with 3 T PC-MRI for cerebral blood flow measurements. We found that cerebral blood flow velocity measured in the ICA was lower using PC-MRI than CDUS (left ICA: PC-MRI, 18.0 +/- 4.2 vs. CDUS, 25.6 +/- 8.6 cm/s; right ICA: PC-MRI, 18.5 +/- 4.8 vs. CDUS, 26.6 +/- 6.7 cm/s, both p < 0.01). However, ICA diameters measured using PC-MRI were larger (left ICA: PC-MRI, 4.7 +/- 0.50 vs. CDUS, 4.1 +/- 0.46 mm; right ICA: PC-MRI, 4.5 +/- 0.49 vs. CDUS, 4.0 +/- 0.45 mm, both p < 0.01). Cerebral blood flow velocity measured in the left vertebral artery with PC MRI was also lower than CDUS, but no differences in vertebral artery diameter were observed between the methods. Dynamic changes and/or intrinsic physiological fluctuations may have caused these differences in vessel diameter and velocity measurements between the methods. However, estimation of volumetric cerebral blood flow was similar and correlated between the methods despite the presence of large individual differences. These findings support the use of CDUS for cerebral blood flow measurements in the ICA and vertebral artery. PMID- 26873889 TI - Polygenic Risk of Schizophrenia and Cognition in a Population-Based Survey of Older Adults. AB - Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years. PRS were computed for SCZ, bipolar disorder (BD), Major Depressive Disorder (MDD), and Alzheimer's disease (ALZ). SCZ PRS associated with decreased cognitive function (z = -3.00, P = .001, DeltaR (2) = 0.04%), which was largely driven by an association with impaired attention and orientation (z = -3.33, P = 4.3*10(-4), DeltaR (2) = 0.08%). We found no effect of BD or MDD PRS on cognition, in contrast to a robust effect of the APOE4/TOMM40 locus (z = -5.05, P = 2.2*10(-7), DeltaR (2) = 0.36%), which was primarily associated with impaired verbal memory (z = -5.15, P = 1.3*10(-7), DeltaR (2) = 0.21%). APOE4/TOMM40 locus and the ALZ PRS, but not the PRS for SCZ, were associated with greater cognitive decline. In summary, using a large, representative sample of older adults, we found evidence for different degrees of association between polygenic risk for SCZ and genetic risk factors for ALZ on cognitive function and decline, highlighting potential differences in the pathophysiology of cognitive deficits seen in SCZ and ALZ. PMID- 26873892 TI - Warriors. PMID- 26873891 TI - Evaluation of the Multiple Sclerosis Walking Scale-12 (MSWS-12) in a Dutch sample: Application of item response theory. AB - BACKGROUND: The Multiple Sclerosis Walking Scale-12 (MSWS-12) measures walking ability from the patients' perspective. We examined the quality of the MSWS-12 using an item response theory model, the graded response model (GRM). METHODS: A total of 625 unique Dutch multiple sclerosis (MS) patients were included. After testing for unidimensionality, monotonicity, and absence of local dependence, a GRM was fit and item characteristics were assessed. Differential item functioning (DIF) for the variables gender, age, duration of MS, type of MS and severity of MS, reliability, total test information, and standard error of the trait level (theta) were investigated. RESULTS: Confirmatory factor analysis showed a unidimensional structure of the 12 items of the scale, explaining 88% of the variance. Item 2 did not fit into the GRM model. Reliability was 0.93. Items 8 and 9 (of the 11 and 12 item version respectively) showed DIF on the variable severity, based on the Expanded Disability Status Scale (EDSS). However, the EDSS is strongly related to the content of both items. CONCLUSION: Our results confirm the good quality of the MSWS-12. The trait level (theta) scores and item parameters of both the 12- and 11-item versions were highly comparable, although we do not suggest to change the content of the MSWS-12. PMID- 26873890 TI - Aberrant Hippocampal Connectivity in Unmedicated Patients With Schizophrenia and Effects of Antipsychotic Medication: A Longitudinal Resting State Functional MRI Study. AB - To better characterize hippocampal pathophysiology in schizophrenia, we conducted a longitudinal study evaluating hippocampal functional connectivity during resting state, using seeds prescribed in its anterior and posterior regions. We enrolled 34 unmedicated patients with schizophrenia or schizoaffective disorder (SZ) and 34 matched healthy controls. SZ were scanned while off medication, then were treated with risperidone for 6 weeks and re-scanned (n = 22). Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. We found significant dysconnectivity with anterior and posterior hippocampal seeds in unmedicated SZ. Baseline connectivity between the hippocampus and anterior cingulate cortex, caudate nucleus, auditory cortex and calcarine sulcus in SZ predicted subsequent response to antipsychotic medications. These same regions demonstrated changes over the 6-week treatment trial that were correlated with symptomatic improvement. Our findings implicate several neural networks relevant to clinical improvement with antipsychotic medications. PMID- 26873893 TI - Assessment and comparison of student engagement in a variety of physiology courses. AB - Calls for reform in science education have promoted active learning as a means to improve student engagement (SENG). SENG is generally acknowledged to have a positive effect on student learning, satisfaction, and retention. A validated 14 question survey was used to assess SENG in a variety of upper- and lower-level physiology courses, including 100-level Anatomy and Physiology 1, 300-level Animal Physiology, 400-level Advanced Physiology, and 500-level Medical Physiology courses. The results indicated that SENG did not vary consistently by course level, format, or curriculum. The highest levels of SENG were found in the Advanced Physiology course, which included SENG as a primary objective of the course. Physiology student SENG scores were compared with National Survey of Student Engagement (NSSE) scores. The results demonstrated that physiology students enrolled in the Anatomy and Physiology 1 course reported lower levels of SENG than first-year students that completed the NSSE. Students enrolled in the Advanced Physiology course reported higher levels of SENG than fourth-year students that completed the NSSE. Assessment of SENG offers insights as to how engaged students are, identifies where efforts may best be applied to enhance SENG, and provides a baseline measure for future comparisons after targeted course modifications. PMID- 26873894 TI - Central respiratory chemosensitivity and cerebrovascular CO2 reactivity: a rebreathing demonstration illustrating integrative human physiology. AB - One of the most effective ways of engaging students of physiology and medicine is through laboratory demonstrations and case studies that combine 1) the use of equipment, 2) problem solving, 3) visual representations, and 4) manipulation and interpretation of data. Depending on the measurements made and the type of test, laboratory demonstrations have the added benefit of being able to show multiple organ system integration. Many research techniques can also serve as effective demonstrations of integrative human physiology. The "Duffin" hyperoxic rebreathing test is often used in research settings as a test of central respiratory chemosensitivity and cerebrovascular reactivity to CO2. We aimed to demonstrate the utility of the hyperoxic rebreathing test for both respiratory and cerebrovascular responses to increases in CO2 and illustrate the integration of the respiratory and cerebrovascular systems. In the present article, methods such as spirometry, respiratory gas analysis, and transcranial Doppler ultrasound are described, and raw data traces can be adopted for discussion in a tutorial setting. If educators have these instruments available, instructions on how to carry out the test are provided so students can collect their own data. In either case, data analysis and quantification are discussed, including principles of linear regression, calculation of slope, the coefficient of determination (R(2)), and differences between plotting absolute versus normalized data. Using the hyperoxic rebreathing test as a demonstration of the complex interaction and integration between the respiratory and cerebrovascular systems provides senior undergraduate, graduate, and medical students with an advanced understanding of the integrative nature of human physiology. PMID- 26873895 TI - Using paper presentation breaks during didactic lectures improves learning of physiology in undergraduate students. AB - Many studies have emphasized the incorporation of active learning into classrooms to reinforce didactic lectures for physiology courses. This work aimed to determine if presenting classic papers during didactic lectures improves the learning of physiology among undergraduate students. Twenty-two students of health information technology were randomly divided into the following two groups: 1) didactic lecture only (control group) and 2) didactic lecture plus paper presentation breaks (DLPP group). In the control group, main topics of gastrointestinal and endocrine physiology were taught using only the didactic lecture technique. In the DLPP group, some topics were presented by the didactic lecture method (similar to the control group) and some topics were taught by the DLPP technique (first, concepts were covered briefly in a didactic format and then reinforced with presentation of a related classic paper). The combination of didactic lecture and paper breaks significantly improved learning so that students in the DLPP group showed higher scores on related topics compared with those in the control group (P < 0.001). Comparison of the scores of topics taught by only the didactic lecture and those using both the didactic lecture and paper breaks showed significant improvement only in the DLPP group (P < 0.001). Data obtained from the final exam showed that in the DLPP group, the mean score of the topics taught by the combination of didactic lecture and paper breaks was significantly higher than those taught by only didactic lecture (P < 0.05). In conclusion, the combination of paper presentation breaks and didactic lectures improves the learning of physiology. PMID- 26873896 TI - Value of artisanal simulators to train veterinary students in performing invasive ultrasound-guided procedures. AB - Pericardial effusion can lead to cardiac tamponade, which endangers an animal's life. Ultrasound-guided pericardiocentesis is used to remove abnormal liquid; however, it requires technical expertise. In veterinary medical education, the opportunity to teach this procedure to save lives during emergencies is rare; therefore, simulators are recommended for this practice. The present study aimed to create a model that can be made "at home" at low cost for ultrasound-guided pericardiocentesis training and to gather feedback about this model through questionnaires given to the participants. Eighteen professionals and thirty-six students were introduced to the simulator in pairs. After the simulation training session, participants filled out the questionnaire. Participants considered the model strong in the following areas: visualization of the pericardium, the heart, fluid in the pericardium, and fluid decrease during fictitious pericardiocentesis and its realism. They considered the model weak or moderate in the following areas: visualization of the surrounding tissues, difficulty of pericardial puncture, and visualization of the catheter. The professionals classified the realism of the experimental heart as moderate, whereas the undergraduate students classified it as strong. All participants believed that the experimental model could be useful in preparing for a future real situation. This model fulfills the need for a practical, realistic, and cost-effective model for ultrasound-guided pericardiocentesis training. PMID- 26873897 TI - Autonomic modification of intestinal smooth muscle contractility. AB - Intestinal smooth muscle contracts rhythmically in the absence of nerve and hormonal stimulation because of the activity of pacemaker cells between and within the muscle layers. This means that the autonomic nervous system modifies rather than initiates intestinal contractions. The practical described here gives students an opportunity to observe this spontaneous activity and its modification by agents associated with parasympathetic and sympathetic nerve activity. A section of the rabbit small intestine is suspended in an organ bath, and the use of a pressure transducer and data-acquisition software allows the measurement of tension generated by the smooth muscle of intestinal walls. The application of the parasympathetic neurotransmitter ACh at varying concentrations allows students to observe an increase in intestinal smooth muscle tone with increasing concentrations of this muscarinic receptor agonist. Construction of a concentration-effect curve allows students to calculate an EC50 value for ACh and consider some basic concepts surrounding receptor occupancy and activation. Application of the hormone epinephrine to the precontracted intestine allows students to observe the inhibitory effects associated with sympathetic nerve activation. Introduction of the drug atropine to the preparation before a maximal concentration of ACh is applied allows students to observe the inhibitory effect of a competitive antagonist on the physiological response to a receptor agonist. The final experiment involves the observation of the depolarizing effect of K(+) on smooth muscle. Students are also invited to consider why the drugs atropine, codeine, loperamide, and botulinum toxin have medicinal uses in the management of gastrointestinal problems. PMID- 26873899 TI - Surveillance cameras and their use as a dissecting microscope in the teaching of biological sciences. PMID- 26873898 TI - "Sickle cell anemia: tracking down a mutation": an interactive learning laboratory that communicates basic principles of genetics and cellular biology. AB - "Sickle cell anemia: tracking down a mutation" is a full-day, inquiry-based, biology experience for high school students enrolled in genetics or advanced biology courses. In the experience, students use restriction endonuclease digestion, cellulose acetate gel electrophoresis, and microscopy to discover which of three putative patients have the sickle cell genotype/phenotype using DNA and blood samples from wild-type and transgenic mice that carry a sickle cell mutation. The inquiry-based, problem-solving approach facilitates the students' understanding of the basic concepts of genetics and cellular and molecular biology and provides experience with contemporary tools of biotechnology. It also leads to students' appreciation of the causes and consequences of this genetic disease, which is relatively common in individuals of African descent, and increases their understanding of the first principles of genetics. This protocol provides optimal learning when led by well-trained facilitators (including the classroom teacher) and carried out in small groups (6:1 student-to-teacher ratio). This high-quality experience can be offered to a large number of students at a relatively low cost, and it is especially effective in collaboration with a local science museum and/or university. Over the past 15 yr, >12,000 students have completed this inquiry-based learning experience and demonstrated a consistent, substantial increase in their understanding of the disease and genetics in general. PMID- 26873900 TI - Open-box muscle-computer interface: introduction to human-computer interactions in bioengineering, physiology, and neuroscience courses. PMID- 26873901 TI - Development of a framework for graph choice and construction. PMID- 26873902 TI - Hypothesis-driven laboratories: an innovative way to foster learning in physiology laboratory courses. PMID- 26873903 TI - Framing and the health policy process: a scoping review. AB - Framing research seeks to understand the forces that shape human behaviour in the policy process. It assumes that policy is a social construct and can be cast in a variety of ways to imply multiple legitimate value considerations. Frames provide the cognitive means of making sense of the social world, but discordance among them forms the basis of policy contestation. Framing, as both theory and method, has proven to generate considerable insight into the nature of policy debates in a variety of disciplines. Despite its salience for understanding health policy debates; however, little is known about the ways frames influence the health policy process. A scoping review using the Arksey and O'Malley framework was conducted. The literature on framing in the health sector was reviewed using nine health and social science databases. Articles were included that explicitly reported theory and methods used, data source(s), at least one frame, frame sponsor and evidence of a given frame's effect on the health policy process. A total of 52 articles, from 1996 to 2014, and representing 12 countries, were identified. Much of the research came from the policy studies/political science literature (n = 17) and used a constructivist epistemology. The term 'frame' was used as a label to describe a variety of ideas, packaged as values, social problems, metaphors or arguments. Frames were characterized at various levels of abstraction ranging from general ideological orientations to specific policy positions. Most articles presented multiple frames and showed how actors advocated for them in a highly contested political process. Framing is increasingly an important, yet overlooked aspect of the policy process. Further analysis on frames, framing processes and frame conflict can help researchers and policymakers to understand opaque and highly charged policy issues, which may facilitate the resolution of protracted policy controversies. PMID- 26873904 TI - Non-haemodynamic anti-anginal agents in the management of patients with stable coronary artery disease and diabetes: A review of the evidence. AB - Patients with coronary artery disease and concomitant diabetes mellitus tend to have more extensive vessel disease than non-diabetes mellitus coronary artery disease patients, are at high risk of adverse cardiovascular events and suffer from a great anginal burden. Very few trials have specifically addressed the issue of optimal anti-anginal therapy in coronary artery disease patients who also have diabetes mellitus. Among 'classical' anti-anginal agents, recent guidelines do not specifically recommend any molecule over others; however, European Society of Cardiology guidelines acknowledge that favourable data in patients with concomitant diabetes mellitus and coronary artery disease are available for trimetazidine and ranolazine, two anti-anginal agents with a non haemodynamic mechanism of action. The aim of this article is to review available evidence supporting the anti-anginal efficacy of these two drugs in the difficult to-treat population of diabetes mellitus patients, including their effects on glycated haemoglobin (HbA1c), a measure of medium-term glycaemic control. Although direct head-to-head comparisons have not been performed, available evidence favours ranolazine as an effective anti-anginal agent over trimetazidine in this population. In addition, ranolazine lowers HbA1c, indicating that it may improve glycaemic control in patients with diabetes mellitus. Conversely, scanty data are available on the metabolic effects of trimetazidine in this cohort of patients. Thus, ranolazine may represent a valuable therapeutic option in stable coronary artery disease patients with diabetes mellitus. PMID- 26873905 TI - Empagliflozin reduces body weight and indices of adipose distribution in patients with type 2 diabetes mellitus. AB - AIMS: To determine the effects of empagliflozin on adiposity indices among patients with type 2 diabetes mellitus. METHODS: Changes in weight, waist circumference, estimated total body fat, index of central obesity and visceral adiposity index were assessed using analysis of covariance and testing of treatment by strata for age, sex and baseline waist circumference in patients with type 2 diabetes mellitus randomized to blinded treatment with empagliflozin versus placebo in clinical trials of 12 weeks (cohort 1) or 24 weeks (cohort 2) duration. RESULTS: This study comprised 3300 patients (cohort 1, N = 823; cohort 2, N = 2477). Empagliflozin reduced weight, waist circumference and adiposity indices versus placebo in both cohorts. Adjusted mean (95% confidence interval) change from baseline in empagliflozin versus placebo was -1.7 kg (-2.1 to -1.4 kg) and -1.9 kg (-2.1 to -1.7 kg) for body weight (p < 0.001); -1.3 cm (-1.8 to 0.7 cm) and -1.3 cm (-1.7 to -1.0 cm) for waist circumference (p < 0.001); -0.2% (-0.7% to 0.3%; p = 0.45) and -0.3% (-0.7% to 0.0%; p = 0.08) for estimated total body fat; -0.007 (-0.011 to -0.004) and -0.008 (-0.010 to -0.006) for index of central obesity (p < 0.001); and -0.3 (-0.5 to 0.0; p = 0.07) and -0.4 (-0.7 to 0.1; p = 0.003) for visceral adiposity index in cohorts 1 and 2, respectively. Adipose reductions were seen across most age, sex and waist circumference subgroups. CONCLUSION: Empagliflozin significantly reduced weight and adiposity indices with the potential to improve cardiometabolic risk among patients with type 2 diabetes mellitus. PMID- 26873906 TI - Crystal structure of the deglycating enzyme Amadoriase I in its free form and substrate-bound complex. AB - Amadoriases, also known as fructosyl amine oxidases (FAOX), are enzymes that catalyze the de-glycosylation of fructosyl amino acids. As such, they are excellent candidates for the development of enzyme-based diagnostic and therapeutic tools against age- and diabetes-induced protein glycation. However, mostly because of the lack of a complete structural characterization of the different members of the family, the molecular bases of their substrate specificity have yet to be fully understood. The high resolution crystal structures of the free and the substrate-bound form of Amadoriase I shown herein allow for the identification of key structural features that account for the diverse substrate specificity shown by this class of enzymes. This is of particular importance in the context of the rather limited and partially incomplete structural information that has so far been available in the literature on the members of the FAOX family. Moreover, using molecular dynamics simulations, we describe the tunnel conformation and the free energy profile experienced by the ligand in going from bulk water to the catalytic cavity, showing the presence of four gating helices/loops, followed by an "L-shaped" narrow cavity. In summary, the tridimensional architecture of Amadoriase I presented herein provides a reference structural framework for the design of novel enzymes for diabetes monitoring and protein deglycation. Proteins 2016; 84:744-758. (c) 2016 Wiley Periodicals, Inc. PMID- 26873909 TI - Extended synaptotagmin interaction with the fibroblast growth factor receptor depends on receptor conformation, not catalytic activity. PMID- 26873908 TI - Waterpipe smoking among secondary school students in Hong Kong. AB - OBJECTIVES: To examine the prevalence of waterpipe smoking and its associated factors among adolescents in Hong Kong. METHODS: We analyzed data of the School based Survey on Smoking among Students 2012/2013 from a representative sample of 45,857 secondary school students in Hong Kong (mean age 14.8, SD 1.9). We conducted Chi-square tests and t test to compare current (past 30 days) waterpipe users and nonusers by sociodemographic variables and other covariates. Univariate and multivariable logistic regression models were used to examine the factors associated with current waterpipe smoking. RESULTS: Overall, 1.2 % of students reported current waterpipe smoking, of whom 43 % reported concurrent use of cigarettes. Waterpipe was the most popular alternative tobacco product (non cigarette) used by students. Current waterpipe smoking was associated with older age, male sex, higher self-perceived family financial status, poor knowledge about the harm of cigarette smoking, positive attitudes toward smoking, current cigarette smoking, other tobacco use, and alcohol consumption. CONCLUSIONS: Waterpipe smoking was the most popular alternative tobacco product among Hong Kong adolescents. Despite the low prevalence, it should be routinely monitored. Education programs and cessation interventions need to address waterpipe smoking in addition to cigarette smoking. PMID- 26873910 TI - Determination of the knowledge of e-waste disposal impacts on the environment among different gender and age groups in China, Laos, and Thailand. AB - E-waste is the fastest growing waste in the solid waste stream in the urban environment. It has become a widely recognised social and environmental problem; therefore, proper management is vital to protecting the fragile environment from its improper disposal. Questionnaire surveys were conducted to determine the knowledge of environmental impacts of e-waste disposal as it relates to mobile phones among different gender and age groups in China, Laos, and Thailand. The results revealed that gender was positively correlated with their knowledge of the status of environmental conditions (P104) (r = 0.077, n = 1994, p < 0.01) and negatively correlated with their knowledge of how to improve environmental conditions (P105) (r = -0.067, n = 2037, p < 0.01). In addition, an increase in age was positively correlated with respondents' concern over the environmental conditions (P103) (r = 0.052, n = 2077, p < 0.05) and P105 (r = 0.061, n = 2061, p < 0.01) mentioned above. The results indicated that female respondents were less knowledgeable about how to improve environmental conditions than male respondents in the three countries. Knowledge gaps were detected in the respondents, at age ?17, in the three countries, and from age 18-22 to 36-45 or older from Thailand and China, on their knowledge of the existing e-waste-related laws. Thus, an effort to bridge the gaps through initiating proper educational programmes in these two countries is necessary. PMID- 26873911 TI - Greenhouse gas emissions from solid waste in Beijing: The rising trend and the mitigation effects by management improvements. AB - Disposal of solid waste poses great challenges to city managements. Changes in solid waste composition and disposal methods, along with urbanisation, can certainly affect greenhouse gas emissions from municipal solid waste. In this study, we analysed the changes in the generation, composition and management of municipal solid waste in Beijing. The changes of greenhouse gas emissions from municipal solid waste management were thereafter calculated. The impacts of municipal solid waste management improvements on greenhouse gas emissions and the mitigation effects of treatment techniques of greenhouse gas were also analysed. Municipal solid waste generation in Beijing has increased, and food waste has constituted the most substantial component of municipal solid waste over the past decade. Since the first half of 1950s, greenhouse gas emission has increased from 6 CO2-eq Gg y(-1)to approximately 200 CO2-eq Gg y(-1)in the early 1990s and 2145 CO2-eq Gg y(-1)in 2013. Landfill gas flaring, landfill gas utilisation and energy recovery in incineration are three techniques of the after-emission treatments in municipal solid waste management. The scenario analysis showed that three techniques might reduce greenhouse gas emissions by 22.7%, 4.5% and 9.8%, respectively. In the future, if waste disposal can achieve a ratio of 4:3:3 by landfill, composting and incineration with the proposed after-emission treatments, as stipulated by the Beijing Municipal Waste Management Act, greenhouse gas emissions from municipal solid waste will decrease by 41%. PMID- 26873912 TI - Short-term mechanical circulatory support with the Impella 5.0 device for cardiogenic shock at La Pitie-Salpetriere. AB - INTRODUCTION: Cardiogenic shock carries a high mortality rate despite aggressive medical treatment. The Impella(r) Recover(r) LP 5.0 Support System is a microaxial minimally invasive ventricular assist device designed for short-term mechanical circulatory support in low cardiac output states. The aim of this study is to assess the safety of the Impella 5.0 device, using the right axillary artery approach, in cardiogenic shock managed at La Pitie-Salpetriere Hospital. METHODS: Since December 2010 and during a period of 14 months, 14 highly selected patients underwent surgical implantation of an Impella 5.0 device for cardiogenic shock. Demographics, preoperative and postoperative data were retrospectively collected from La Pitie-Salpetriere computerized medical charts. Responders to Impella support were defined as patients with rapid improvement in haemodynamic condition and biological profile. Patients who had no signs of cardiac recovery after two weeks of mechanical support were considered for heart transplantation or long-term left ventricular assist device implantation. RESULTS: Patients were predominantly male (78.5%) with a mean age of 64+/-15. Short-term circulatory support was indicated for cardiogenic shock in the setting of acute coronary syndromes ( n=7; 50%), postcardiotomy cardiac dysfunctions ( n=6; 43%) and anthracycline-induced dilated cardiomyopathy ( n=1; 7%). After a mean support time of 8.5 days, six patients (42.8%) were successfully weaned and four (28.5%) were switched to a long-term left ventricular assist device. No major bleeding, arm ischaemia, ventricular arrhythmia or severe haemolysis was noted. We report two cases (14%) of pump thrombosis, four cases of device displacement with the need of pump repositioning and one case (7%) of infection at the insertion site. Thirty-day mortality was 35.7%. Long-term overall mortality rate at six months, one year and two years was 42.8, 42.8 and 42.8%, respectively. CONCLUSIONS: The Impella 5.0 device surgically inserted through the axillary artery is a valuable minimally invasive short-term circulatory support in cardiogenic shock of various aetiologies. PMID- 26873913 TI - Health literacy and chronic disease management: drawing from expert knowledge to set an agenda. AB - Understanding the nature and impact of health literacy is a priority in health promotion and chronic disease prevention and treatment. Health literacy comprises the application of a broad set of skills to access, comprehend, evaluate, communicate and act on health information for improved health and well-being. A complex concept, it involves multiple participants and is enacted across a wide variety of contexts. Health literacy's complexity has given rise to challenges achieving a standard definition and developing means to measure all its dimensions. In May 2013, a group of health literacy experts, clinicians and policymakers convened at an Expert Roundtable to review the current state of health literacy research and practice, and make recommendations about refining its definition, expanding its measurement and integrating best practices into chronic disease management. The four-day knowledge exchange concluded that the successful integration of health literacy into policy and practice depends on the development of a more substantial evidence base. A review of the successes and gaps in health literacy research, education and interventions culminated in the identification of key priorities to further the health literacy agenda. The workshop was funded by the UBC Peter Wall Institute for Advanced Studies, Vancouver. PMID- 26873914 TI - [Is the introduction of innovative methods in cardiovascular diagnostics and therapy to quick?]. AB - Andreas Gruntzig can be regarded as the pioneer of modern cardiology. Based on the previous experiences of Charles Dotter in Portland, Oregon, and after many years of preparation as a young 38-year-old physician and consultant he carried out the first percutaneous transluminal coronary angioplasty (PTCA) in a 38-year old patient in Zurich in 1977, supported by the cardiac surgeons A. Senning and M. Turina. Despite high ranking publications and early preparedness to share his experiences the development of PTCA stagnated and was met with great scepticism. The technique was new, technically difficult and aimed at aortocoronary bypass surgery, which was itself still in its infancy 10 years after the introduction in Cleveland in 1968. Even after several years only two patients per week were admitted for treatment in Zurich. In a similar way the young cardiac surgeon H.R. Andersen was a pioneer in Denmark whose ideas and own experiments with a balloon catheter-assisted aortic valve implantation were not initially taken up by the leading companies of the time and publication of the data suffered lengthy delays. It took 10 years before Prof. A. Cribier in Rouen followed up his ideas and carried out the first valve implantation again in pioneer work after many years of preparation in 2002. Again, the new method for treatment of very old and high risk patients needed many years before it was accepted. The breakthrough only became possible when this new technique began to be used in cardiac surgery after the introduction of hybrid cardiac catheter operating rooms. Despite evidence-based studies innovative methods are not subject to the same criteria throughout Europe with respect to the timely introduction of innovative and validated procedures also in consideration of reimbursement and this has become an important initiative of the European Society of Cardiology (ESC). PMID- 26873915 TI - [We implant too many ICD - contra]. AB - Based on prospective population-based cohort studies from the Netherlands approximately 120,000 sudden cardiac deaths (SCD) have to be assumed in 2014 in Germany for persons older than 55 years of age without an implantable cardioverter defibrillator (ICD). In contrast in 2014 only 30,000 ICD were implanted in Germany. Due to the fact that victims of SCD are difficult to predict many more implantations are actually necessary because only approximately one third of the patients use their ICD during battery running time. Also according to the largest ICD study on ischemic cardiomyopathy at least six patients must be treated with an ICD to save one life after 8 years. Guidelines for ICD implantation are based on 12 randomized studies with more than 9000 patients. In 2014 in Germany 94 % of ICD implantations were carried out in accordance with the guidelines. The most important studies for primary prophylaxis of SCD (MADIT 2 and SCD-HeFT) finished recruitment of patients in 2001 but propensity score-matched ICD patients from a large national data base showed identical survival curves in 2005 and 2006. New ICD developments in recent years, such as suppression of inappropriate ICD therapy by improved programming, cardiac resynchronization, and telemonitoring showed promise for current ICD patients of improved survival in comparison to the original randomized patients from the studies, which led to the indications in the guidelines. PMID- 26873916 TI - Inflammatory fibroid polyp (Vanek's tumour): my worst nightmare in the emergency department. AB - A middle-aged woman presented in shock with bleeding per rectum for 2 days without any significant past medical or surgical illness. Abdominal sonography, oesophagogastroduodenoscopy and sigmoidocolonoscopy were unremarkable. Despite 6 units of blood transfusion, 3000 mL of plasma expanders and ionotropes, the arterial pressure gradually decreased. We had no choice but to undergo life threatening yet possibly life saving laparotomy. We found a 1*1 cm ileal bleeding mucosal polyp about 20 cm away from the ileocaecal junction. We resected and anastomosed end to end. Perioperatively, the patient was transfused with another 4 units of blood product. Immunohistopathology revealed a large number of CD34 positive spindle cells and eosinophils with extensive thick-walled capillaries compatible with inflammatory fibroid polyp. This case of Vanek's tumour is reported for its atypical site, which presented as massive obscure gastrointestinal haemorrhage without any prior warning signs. PMID- 26873917 TI - Sigmoid vaginoplasty in testicular feminising syndrome: surgical technique, outcome and review of the literature. AB - Vaginal agenesis occurs in approximately 1:5000 live female births. It results from failure of the sinovaginal bulbs to develop and form the vaginal plate. Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is the most common cause of vaginal absence followed by complete or partial androgen insensitivity syndrome. Treatment of these patients encompasses a spectrum from simple non-operative dilation to the more complicated surgical creation of a neovagina. We present a case of a patient with testicular feminising syndrome who was reared as a female and underwent bilateral gonadal excision and sigmoid vaginoplasty. PMID- 26873918 TI - Fulminant zygomycosis of graft liver following liver transplantation. AB - A 44-year-old man with hepatitis B virus (HBV)-related cirrhosis underwent living donor liver transplantation at our institute. Induction of immunosuppression was achieved with basiliximab, due to deranged renal function, and maintained with prednisolone, tacrolimus and mycophenolate mofetil. The intraoperative and immediate postoperative periods were fairly uneventful. A duplex scan, taken during the third week post-transplantation due to sudden rise in liver enzymes, revealed multifocal hypoechoic lesions in the graft liver with normal Doppler parameters. Multidetecor computed tomography (MDCT) showed multiple hypodense vessel-sparing lesions in the graft liver. Cultures from the aspirate grew filamentous fungi identified as Basidiobolus ranarum species. Despite multiple broad spectrum antifungal infusions including liposomal amphotericin, itraconazole, caspofungin and posaconazole, serial sonography showed the hepatic lesions increasing in size, and involving segments V, VI and VII. The patient developed severe liver dysfunction ultimately progressing to sepsis, multiorgan dysfunction and death. PMID- 26873919 TI - Dasatinib improves insulin sensitivity and affects lipid metabolism in a patient with chronic myeloid leukaemia. AB - A 65-year-old woman had been visiting our department for the treatment of type-2 diabetes mellitus since December 2012. Her glycated haemoglobin levels were well controlled (~5.8% (40 mmol/mol)) by metformin (500 mg). In July 2014, her white cell count increased suddenly to 33 530 cells/MUL and she was diagnosed with Ph+ chronic myeloid leukaemia. She was started on dasatinib (100 mg), which immediately normalised plasma levels of WCC. Dasatinib improved the glycaemic index to <6.0% and also improved plasma levels of triglycerides (TGs) and high density lipoprotein-cholesterol (HDL-c). Levels of low-density lipoprotein cholesterol were increased but remained within the normal range. The TG:HDL-c ratio and Quantitative Insulin Sensitivity Check Index rapidly improved. Followed by an improvement in insulin sensitivity, plasma levels of adiponectin and leptin were increased. This case study suggests that dasatinib might have positive as well as negative effects on the metabolism of glucose and lipids. PMID- 26873920 TI - Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction. AB - Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128-132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ~38% (P < 0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r(2 )= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P < 0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic-euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and metabolic response to insulin, which support myocardial function and growth. PMID- 26873921 TI - Initiation on the divergent Type I cadicivirus IRES: factor requirements and interactions with the translation apparatus. AB - Cadicivirus (CDV) is unique amongst picornaviruses in having a dicistronic genome with internal ribosomal entry sites (IRESs) preceding both open reading frames. Here, we investigated initiation on the 5'-terminal IRES. We report that the 982 nt long 5'UTR comprises 12 domains (d1-d12), five of which (d8-d12, nts 341-950) constitute a divergent Type I IRES. It comprises central elements (the apex of d10, d11 and the following polypyrimidine tract) that are homologous to corresponding elements in canonical Type 1 IRESs, and non-canonical flanking domains (d8, d9 and d12). In vitro reconstitution revealed that as with canonical Type I IRESs, 48S complex formation requires eukaryotic initiation factors (eIFs) 1, 1A, 2, 3, 4A, 4B and 4G, and the poly(C) binding protein 2 (PCBP2), and starts with specific binding of eIF4G/eIF4A to d11. However, in contrast to canonical Type I IRESs, subsequent recruitment of 43S ribosomal complexes does not require direct interaction of their eIF3 constituent with the IRES-bound eIF4G. On the other hand, the CDV IRES forms a 40S/eIF3/IRES ternary complex, with multiple points of contact. These additional interactions with translational components could potentially stimulate recruitment of the 43S complex and alleviate the necessity for direct eIF4G/eIF3 interaction. PMID- 26873922 TI - Small activating RNA binds to the genomic target site in a seed-region-dependent manner. AB - RNA activation (RNAa) is the upregulation of gene expression by small activating RNAs (saRNAs). In order to investigate the mechanism by which saRNAs act in RNAa, we used the progesterone receptor (PR) gene as a model, established a panel of effective saRNAs and assessed the involvement of the sense and antisense strands of saRNA in RNAa. All active saRNAs had their antisense strand effectively incorporated into Ago2, whereas such consistency did not occur for the sense strand. Using a distal hotspot for saRNA targeting at 1.6-kb upstream from the PR transcription start site, we further established that gene activation mediated by saRNA depended on the complementarity of the 5' region of the antisense strand, and that such activity was largely abolished by mutations in this region of the saRNA. We found markedly reduced RNAa effects when we created mutations in the genomic target site of saRNA PR-1611, thus providing evidence that RNAa depends on the integrity of the DNA target. We further demonstrated that this saRNA bound the target site on promoter DNA. These results demonstrated that saRNAs work via an on-site mechanism by binding to target genomic DNA in a seed-region-dependent manner, reminiscent of miRNA-like target recognition. PMID- 26873925 TI - The Importance of Spiritual Care in Nursing Practice. AB - PURPOSE: Explore what spiritual care means to nurses who work in emergency care units. DESIGN AND METHOD: Nine nursing professionals from an emergency care unit at a private health institution affiliated with the Universidad de La Sabana participated in this descriptive qualitative study. Nonparticipant observation, field notes, and in-depth interviews with a question guide were used to collect the data, which were analyzed by means of content analysis. RESULTS: Three themes and their corresponding subthemes were identified with respect to the significance of spiritual care: (1) interpretation of spiritual care, (2) the patient and the family in spiritual care, and (3) the role of the nurse in spiritual care. CONCLUSIONS: These findings provide a deeper understanding of spiritual care in terms of its significance. They also acknowledge its importance to nursing practice in emergency care units. The significance of spiritual care is based on theoretical, scientific, and humanistic points of reference (the discipline of nursing) that strengthen the therapeutic relationship between the patient/family-nurse dyad. The study also offers evidence for holistic nursing practice that requires theoretical-academic, administrative, and assistance support. PMID- 26873924 TI - Circular RNA profile in gliomas revealed by identification tool UROBORUS. AB - Recent evidence suggests that many endogenous circular RNAs (circRNAs) may play roles in biological processes. However, the expression patterns and functions of circRNAs in human diseases are not well understood. Computationally identifying circRNAs from total RNA-seq data is a primary step in studying their expression pattern and biological roles. In this work, we have developed a computational pipeline named UROBORUS to detect circRNAs in total RNA-seq data. By applying UROBORUS to RNA-seq data from 46 gliomas and normal brain samples, we detected thousands of circRNAs supported by at least two read counts, followed by successful experimental validation on 24 circRNAs from the randomly selected 27 circRNAs. UROBORUS is an efficient tool that can detect circRNAs with low expression levels in total RNA-seq without RNase R treatment. The circRNAs expression profiling revealed more than 476 circular RNAs differentially expressed in control brain tissues and gliomas. Together with parental gene expression, we found that circRNA and its parental gene have diversified expression patterns in gliomas and control brain tissues. This study establishes an efficient and sensitive approach for predicting circRNAs using total RNA-seq data. The UROBORUS pipeline can be accessed freely for non-commercial purposes at http://uroborus.openbioinformatics.org/. PMID- 26873926 TI - The Association Between Pain and Quality of Life for Patients With Cancer in an Outpatient Clinic, an Inpatient Oncology Ward, and Inpatient Palliative Care Units. AB - PURPOSE: This study was designed to clarify the association between pain and quality of life (QOL) of Japanese patients with cancer using a cancer-specific QOL scale (European Organization for Research and Treatment of Cancer [EORTC] QLQ C15-PAL) in 3 care settings (outpatient, inpatient, and palliative care units [PCUs]). METHODS: We examined the above-mentioned purpose for the total of 404 patients. RESULTS: In outpatients, physical, emotional functioning (EF), and global health status/QOL (QL item) were significantly correlated with average pain, and their correlation coefficients were -0.37 to -0.46 (P < .0001). In inpatients, they were -0.33 (P = .006), -0.26 (P = .030), and -0.31 (P = .012). In the PCU patients, they were -0.12 (P = .316), -0.30 (P = .009), and -0.28 (P = .015). CONCLUSION: Patients' pain had an association with physical and emotional QOL, and the association was smaller in the PCU patients than the others. PMID- 26873923 TI - Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors. AB - RAD52 is a member of the homologous recombination (HR) pathway that is important for maintenance of genome integrity. While single RAD52 mutations show no significant phenotype in mammals, their combination with mutations in genes that cause hereditary breast cancer and ovarian cancer like BRCA1, BRCA2, PALB2 and RAD51C are lethal. Consequently, RAD52 may represent an important target for cancer therapy. In vitro, RAD52 has ssDNA annealing and DNA strand exchange activities. Here, to identify small molecule inhibitors of RAD52 we screened a 372,903-compound library using a fluorescence-quenching assay for ssDNA annealing activity of RAD52. The obtained 70 putative inhibitors were further characterized using biochemical and cell-based assays. As a result, we identified compounds that specifically inhibit the biochemical activities of RAD52, suppress growth of BRCA1- and BRCA2-deficient cells and inhibit RAD52-dependent single-strand annealing (SSA) in human cells. We will use these compounds for development of novel cancer therapy and as a probe to study mechanisms of DNA repair. PMID- 26873927 TI - An efficient gene-gene interaction test for genome-wide association studies in trio families. AB - MOTIVATION: Several efficient gene-gene interaction tests have been developed for unrelated case-control samples in genome-wide association studies (GWAS), making it possible to test tens of billions of interaction pairs of single-nucleotide polymorphisms (SNPs) in a reasonable timeframe. However, current family-based gene-gene interaction tests are computationally expensive and are not applicable to genome-wide interaction analysis. RESULTS: We developed an efficient family based gene-gene interaction test, GCORE, for trios (i.e. two parents and one affected sib). The GCORE compares interlocus correlations at two SNPs between the transmitted and non-transmitted alleles. We used simulation studies to compare the statistical properties such as type I error rates and power for the GCORE with several other family-based interaction tests under various scenarios. We applied the GCORE to a family-based GWAS for autism consisting of approximately 2000 trios. Testing a total of 22 471 383 013 interaction pairs in the GWAS can be finished in 36 h by the GCORE without large-scale computing resources, demonstrating that the test is practical for genome-wide gene-gene interaction analysis in trios. AVAILABILITY AND IMPLEMENTATION: GCORE is implemented with C ++ and is available at http://gscore.sourceforge.net CONTACT: rchung@nhri.org.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26873928 TI - SplAdder: identification, quantification and testing of alternative splicing events from RNA-Seq data. AB - MOTIVATION: Understanding the occurrence and regulation of alternative splicing (AS) is a key task towards explaining the regulatory processes that shape the complex transcriptomes of higher eukaryotes. With the advent of high-throughput sequencing of RNA (RNA-Seq), the diversity of AS transcripts could be measured at an unprecedented depth. Although the catalog of known AS events has grown ever since, novel transcripts are commonly observed when working with less well annotated organisms, in the context of disease, or within large populations. Whereas an identification of complete transcripts is technically challenging and computationally expensive, focusing on single splicing events as a proxy for transcriptome characteristics is fruitful and sufficient for a wide range of analyses. RESULTS: We present SplAdder, an alternative splicing toolbox, that takes RNA-Seq alignments and an annotation file as input to (i) augment the annotation based on RNA-Seq evidence, (ii) identify alternative splicing events present in the augmented annotation graph, (iii) quantify and confirm these events based on the RNA-Seq data and (iv) test for significant quantitative differences between samples. Thereby, our main focus lies on performance, accuracy and usability. AVAILABILITY: Source code and documentation are available for download at http://github.com/ratschlab/spladder Example data, introductory information and a small tutorial are accessible via http://bioweb.me/spladder CONTACTS: : andre.kahles@ratschlab.org or gunnar.ratsch@ratschlab.org SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26873929 TI - Gene expression inference with deep learning. AB - MOTIVATION: Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ~1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. RESULTS: We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. AVAILABILITY AND IMPLEMENTATION: D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26873930 TI - Trinculo: Bayesian and frequentist multinomial logistic regression for genome wide association studies of multi-category phenotypes. AB - MOTIVATION: For many classes of disease the same genetic risk variants underly many related phenotypes or disease subtypes. Multinomial logistic regression provides an attractive framework to analyze multi-category phenotypes, and explore the genetic relationships between these phenotype categories. We introduce Trinculo, a program that implements a wide range of multinomial analyses in a single fast package that is designed to be easy to use by users of standard genome-wide association study software. AVAILABILITY AND IMPLEMENTATION: An open source C implementation, with code and binaries for Linux and Mac OSX, is available for download at http://sourceforge.net/projects/trinculo SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: lj4@well.ox.ac.uk. PMID- 26873932 TI - An empirical Bayes change-point model for identifying 3' and 5' alternative splicing by next-generation RNA sequencing. AB - MOTIVATION: Next-generation RNA sequencing (RNA-seq) has been widely used to investigate alternative isoform regulations. Among them, alternative 3 ': splice site (SS) and 5 ': SS account for more than 30% of all alternative splicing (AS) events in higher eukaryotes. Recent studies have revealed that they play important roles in building complex organisms and have a critical impact on biological functions which could cause disease. Quite a few analytical methods have been developed to facilitate alternative 3 ': SS and 5 ': SS studies using RNA-seq data. However, these methods have various limitations and their performances may be further improved. RESULTS: We propose an empirical Bayes change-point model to identify alternative 3 ': SS and 5 ': SS. Compared with previous methods, our approach has several unique merits. First of all, our model does not rely on annotation information. Instead, it provides for the first time a systematic framework to integrate various information when available, in particular the useful junction read information, in order to obtain better performance. Second, we utilize an empirical Bayes model to efficiently pool information across genes to improve detection efficiency. Third, we provide a flexible testing framework in which the user can choose to address different levels of questions, namely, whether alternative 3 ': SS or 5 ': SS happens, and/or where it happens. Simulation studies and real data application have demonstrated that our method is powerful and accurate. AVAILABILITY AND IMPLEMENTATION: The software is implemented in Java and can be freely downloaded from http://ebchangepoint.sourceforge.net/ CONTACT: zhiwei@njit.edu. PMID- 26873931 TI - Privacy-preserving microbiome analysis using secure computation. AB - MOTIVATION: Developing targeted therapeutics and identifying biomarkers relies on large amounts of research participant data. Beyond human DNA, scientists now investigate the DNA of micro-organisms inhabiting the human body. Recent work shows that an individual's collection of microbial DNA consistently identifies that person and could be used to link a real-world identity to a sensitive attribute in a research dataset. Unfortunately, the current suite of DNA-specific privacy-preserving analysis tools does not meet the requirements for microbiome sequencing studies. RESULTS: To address privacy concerns around microbiome sequencing, we implement metagenomic analyses using secure computation. Our implementation allows comparative analysis over combined data without revealing the feature counts for any individual sample. We focus on three analyses and perform an evaluation on datasets currently used by the microbiome research community. We use our implementation to simulate sharing data between four policy domains. Additionally, we describe an application of our implementation for patients to combine data that allows drug developers to query against and compensate patients for the analysis. AVAILABILITY AND IMPLEMENTATION: The software is freely available for download at: http://cbcb.umd.edu/~hcorrada/projects/secureseq.html SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: hcorrada@umiacs.umd.edu. PMID- 26873933 TI - Selecting a classification function for class prediction with gene expression data. AB - MOTIVATION: Class predicting with gene expression is widely used to generate diagnostic and/or prognostic models. The literature reveals that classification functions perform differently across gene expression datasets. The question, which classification function should be used for a given dataset remains to be answered. In this study, a predictive model for choosing an optimal function for class prediction on a given dataset was devised. RESULTS: To achieve this, gene expression data were simulated for different values of gene-pairs correlations, sample size, genes' variances, deferentially expressed genes and fold changes. For each simulated dataset, ten classifiers were built and evaluated using ten classification functions. The resulting accuracies from 1152 different simulation scenarios by ten classification functions were then modeled using a linear mixed effects regression on the studied data characteristics, yielding a model that predicts the accuracy of the functions on a given data. An application of our model on eight real-life datasets showed positive correlations (0.33-0.82) between the predicted and expected accuracies. CONCLUSION: The here presented predictive model might serve as a guide to choose an optimal classification function among the 10 studied functions, for any given gene expression data. AVAILABILITY AND IMPLEMENTATION: The R source code for the analysis and an R package 'SPreFuGED' are available at Bioinformatics online. CONTACT: v.l.jong@umcutecht.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26873934 TI - "Turn Up the Taste": Assessing the Role of Taste Intensity and Emotion in Mediating Crossmodal Correspondences between Basic Tastes and Pitch. AB - People intuitively match basic tastes to sounds of different pitches, and the matches that they make tend to be consistent across individuals. It is, though, not altogether clear what governs such crossmodal mappings between taste and auditory pitch. Here, we assess whether variations in taste intensity influence the matching of taste to pitch as well as the role of emotion in mediating such crossmodal correspondences. Participants were presented with 5 basic tastants at 3 concentrations. In Experiment 1, the participants rated the tastants in terms of their emotional arousal and valence/pleasantness, and selected a musical note (from 19 possible pitches ranging from C2 to C8) and loudness that best matched each tastant. In Experiment 2, the participants made emotion ratings and note matches in separate blocks of trials, then made emotion ratings for all 19 notes. Overall, the results of the 2 experiments revealed that both taste quality and concentration exerted a significant effect on participants' loudness selection, taste intensity rating, and valence and arousal ratings. Taste quality, not concentration levels, had a significant effect on participants' choice of pitch, but a significant positive correlation was observed between individual perceived taste intensity and pitch choice. A significant and strong correlation was also demonstrated between participants' valence assessments of tastants and their valence assessments of the best-matching musical notes. These results therefore provide evidence that: 1) pitch-taste correspondences are primarily influenced by taste quality, and to a lesser extent, by perceived intensity; and 2) such correspondences may be mediated by valence/pleasantness. PMID- 26873935 TI - Alteration of Duration Mismatch Negativity Induced by Transcranial Magnetic Stimulation Over the Left Parietal Lobe. AB - Mismatch negativity (MMN) is generated by a comparison between an incoming sound and the memory trace of preceding sounds stored in sensory memory without any attention to the sound. N100 (N1) is associated with the afferent response to sound onset and reflects early analysis of stimulus characteristics. MMN generators are present in the temporal and frontal lobe, and N1 generators are present in the temporal lobe. The parietal lobe is involved in MMN generation elicited by a change in duration. The anatomical network connecting these areas, lateralization, and the effect of the side of ear stimulation on MMN remain unknown. Thus, we studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left parietal lobe on MMN and N1 in 10 healthy subjects. Low-frequency rTMS over the left parietal lobe decreased the amplitude of MMN following right ear sound stimulation, but the amplitude was unaffected with left ear sound stimulation. We observed no significant changes in the amplitude of N1 or the latency of MMN or N1. These results suggest that low frequency rTMS over the left parietal lobe modulates the detection of early auditory changes in duration in healthy subjects. Stimulation that is contralateral to the side of the ear experiencing sound may affect the generation of duration MMN more than ipsilateral stimulation. PMID- 26873936 TI - Human plasma platelet-derived exosomes: effects of aspirin. AB - Platelet-derived exosomes mediate platelet atherogenic interactions with endothelial cells and monocytes. A new method for isolation of plasma platelet derived exosomes is described and used to examine effects of aging and aspirin on exosome cargo proteins. Exosome secretion by purified platelets in vitro did not increase after exposure to thrombin or collagen, as assessed by exosome counts and quantification of the CD81 exosome marker. Thrombin and collagen increased exosome content of alpha-granule chemokines CXCL4 and CXCL7 and cytoplasmic high mobility group box 1 (HMGB1) protein, but not membrane platelet glycoprotein VI (GPVI), with dependence on extracellular calcium. Aspirin consumption significantly blocked thrombin- and collagen-induced increases in exosome cargo levels of chemokines and HMGB1, without altering total exosome secretion or GPVI cargo. Plasma platelet-derived exosomes, enriched by absorption with mouse antihuman CD42b [platelet glycoprotein Ib (GPIb)] mAb, had sizes and cargo protein contents similar to those of exosomes from purified platelets. The plasma platelet-derived exosome number is lower and its chemokine and HMGB1 levels higher after age 65 yr. Aspirin consumption significantly suppressed cargo protein levels of plasma platelet-derived exosomes without altering total levels of exosomes. Cargo proteins of human plasma platelet-derived exosomes may biomark platelet abnormalities and in vivo effects of drugs.- Goetzl, E. J., Goetzl, L., Karliner, J. S., Tang, N., Pulliam, L. Human plasma platelet-derived exosomes: effects of aspirin. PMID- 26873939 TI - Enabling digital pathology in the diagnostic setting: navigating through the implementation journey in an academic medical centre. AB - AIMS: As digital pathology (DP) and whole slide imaging (WSI) technology advance and mature, there is an increasing drive to incorporate DP into the diagnostic environment. However, integration of DP into the diagnostic laboratory is a non trivial task and filled with unexpected challenges unlike standalone implementations. We share our journey of implementing DP in the diagnostic laboratory setting, highlighting seven key guiding principles that drive the progression through implementation into deployment and beyond. METHODS: The DP implementation with laboratory information system integration was completed in 8 months, including validation of the solution for diagnostic use in accordance with College of American Pathologists guidelines. We also conducted prospective validation via paired delivery of glass slides and WSI to our pathologists postdeployment. RESULTS: Common themes in our guiding principles included emphasis on workflow and being comprehensive in the approach, looking beyond pathologist user champions and expanding into an extended project team involving laboratory technicians, clerical/data room staff and archival staff. Concordance between glass slides and WSI ranged from 93% to 100% among various applications on validation. We also provided equal opportunities for every pathologist throughout the department to be competent and confident with DP through prospective validation, with overall concordance of 96% compared with glass slides, allowing appreciation of the advantages and limitations of WSI, hence enabling the use of DP as a useful diagnostic modality. CONCLUSIONS: Smooth integration of DP into the diagnostic laboratory is possible with careful planning, discipline and a systematic approach adhering to our guiding principles. PMID- 26873938 TI - Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension. AB - Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 +/- 130 to 1664 +/- 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 +/- 1.5% vs. 31 +/- 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 +/- 0.2 vs. 3.5 +/- 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES(-/-) knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 +/- 5% in wild type Ang II vs. 15 +/- 4% in RANTES(-/-)), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-gamma-producing CD8(+) and double-negative CD3(+)CD4(-)CD8(-) T cells in perivascular space and reduced vascular oxidative stress while FoxP3(+) T-regulatory cells were unaltered. IFN-gamma ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = -0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.-Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension. PMID- 26873937 TI - Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium. AB - Agonist-mediated signaling by the endothelium controls virtually all vascular functions. Because of the large diversity of agonists, each with varying concentrations, background noise often obscures individual cellular signals. How the endothelium distinguishes low-level fluctuations from noise and decodes and integrates physiologically relevant information remains unclear. Here, we recorded changes in intracellular Ca(2+) concentrations in response to acetylcholine in areas encompassing hundreds of endothelial cells from inside intact pressurized arteries. Individual cells responded to acetylcholine with a concentration-dependent increase in Ca(2+) signals spanning a single order of magnitude. Interestingly, however, intercellular response variation extended over 3 orders of magnitude of agonist concentration, thus crucially enhancing the collective bandwidth of endothelial responses to agonists. We also show the accuracy of this collective mode of detection is facilitated by spatially restricted clusters of comparably sensitive cells arising from heterogeneous receptor expression. Simultaneous stimulation of clusters triggered Ca(2+) signals that were transmitted to neighboring cells in a manner that scaled with agonist concentration. Thus, the endothelium detects agonists by acting as a distributed sensing system. Specialized clusters of detector cells, analogous to relay nodes in modern communication networks, integrate populationwide inputs, and enable robust noise filtering for efficient high-fidelity signaling.-Wilson, C., Saunter, C. D., Girkin, J. M., McCarron, J. G. Clusters of specialized detector cells provide sensitive and high fidelity receptor signaling in the intact endothelium. PMID- 26873940 TI - Depression predictors within six months of ischemic stroke: The DEPRESS Study. AB - BACKGROUND: Depression negatively affects rehabilitation and quality of life after stroke. Identifying in the acute phase patients at high risk for post stroke depression would facilitate early detection of depressive symptoms. METHODS: The DEPRESS (Depression Predictors after Ischemic Stroke) study was a prospective cohort study designed to identify baseline predictors of depression occurring within six months after ischemic stroke and high-risk patients for post stroke depression. All patients without aphasia were screened for depression by a neurologist using the Patient Health Questionnaire, and the diagnosis was confirmed by a psychiatrist with the Mini International Neuropsychiatric Interview. In severely aphasic patients, depression was diagnosed using the Aphasic Depression Rating Scale and the Visual Analog Mood Scale. RESULTS: Depression was present in 61 of 251 (24%) patients enrolled in the DEPRESS study. Female gender, prior history of depression, major physical disability, prior history of stroke, stressful life event exposure in the month preceding stroke onset, and pathologic crying were significant predictors of depression within six months after ischemic stroke. Depression was more frequent in patients with left caudate and/or lenticular nucleus lesion (OR = 2.4, 95% confidence interval, 0.97 5.91), but the difference was not significant. The presence of >=2 predictors identified the largest proportion of depressed patients (62%) in the smallest proportion of the cohort (36%). CONCLUSION: Female gender, prior history of depression, major physical disability, prior history of stroke, recent stressful life event exposure before stroke, and pathologic crying were significant predictors of post-stroke depression occurring within six months after stroke onset. PMID- 26873941 TI - The role of adipokines in ischemic stroke risk stratification. AB - BACKGROUND: Adiponectin, leptin, and resistin are the most well-studied adipokines and play important roles in the regulation of glucose metabolism, subclinical inflammation, and cardiovascular homeostasis. Accordingly, measurement of adipokine levels might be useful in cardiovascular risk stratification. Moreover, the study of single-nucleotide polymorphisms of genes that encode these adipokines might also represent a valuable predictive tool in cardiovascular disease prevention strategies. AIMS: To summarize the biologic role of the adipokines adiponectin, leptin, and resistin and the prognostic value of their serum levels regarding the occurrence and outcome of ischemic stroke. We also discuss the relationship of single-nucleotide polymorphisms of the adiponectin, leptin genes, and the -420C > G polymorphism of resistin gene with stroke risk. SUMMARY OF REVIEW: Several studies in the general population evaluated the association between these adipokines and stroke risk, yielding conflicting results. There are more limited data regarding the effect of these adipokines on stroke severity and outcome. A small number of studies also assessed the predictive role of single-nucleotide polymorphisms of the adiponectin, leptin, and resistin genes regarding stroke risk, but the findings were also controversial. CONCLUSIONS: It is unclear whether adiponectin, leptin, and resistin levels or the single-nucleotide polymorphisms of their encoding genes are independently associated with stroke risk. However, given the role of these adipokines in the pathogenesis of atherosclerosis, larger prospective studies, both in the general population and in patients with a history of stroke, are needed to determine whether the measurement of serum levels of these adipokines or the evaluation of single-nucleotide polymorphisms in their encoding genes could improve stroke risk prediction. If this relationship is proven, therapeutic interventions targeting adipokine levels might represent a novel approach to reduce stroke-related mortality and disability. PMID- 26873942 TI - Detection of Silent Atrial Fibrillation aFter Ischemic StrOke (SAFFO) guided by implantable loop recorder: multicentre Italian trial based on stroke unit network with paired cardio-arrhythmology units (Italian Neurocardiology Unit Network). AB - RATIONALE: Atrial fibrillation is associated with a high risk of stroke and its prevalence increases in subjects aged >=65 years. After an ischemic stroke, the use of standard monitoring methods may underestimate the detection rate of atrial fibrillation. Hence, it is very likely that even patients having a first atherothrombotic or lacunar stroke with high burden of vascular risk factors are exposed to increased risk of developing atrial fibrillation in the subsequent years and atrial fibrillation may be the cause underlying possible recurrent strokes AIM AND HYPOTHESIS: The Silent Atrial Fibrillation aFter Ischemic StrOke (SAFFO) trial has the objective to evaluate the detection of atrial fibrillation or atrial flutter as first diagnosis by implantable loop recorder in patients with first-ever atherothrombotic or lacunar stroke. We hypothesize that the detection will be higher than that observed by using standard cardiac monitoring METHODS AND DESIGN: SAFFO is a prospective, multicenter, randomized, controlled, open-label trial with blinded assessment of outcome measures. Patients who fulfill inclusion criteria will be randomized to either continuous monitoring using an implantable loop recorder plus standard monitoring (intervention arm) or standard heart rhythm monitoring alone (control arm) with a ratio of 1:1 STUDY OUTCOMES: The primary endpoint is the detection of atrial fibrillation/atrial flutter as first diagnosis in the first 12 months of the study period DISCUSSION: If positive, SAFFO trial could have important clinical implications in terms of changing the standard diagnostic protocol in patients with atherothrombotic and lacunar stroke, and of increasing the shift of secondary prevention treatment from antiplatelet to anticoagulant therapy. PMID- 26873945 TI - Multiple giant bullae of the lung mimicking massive pneumothorax in a patient with osteogenesis imperfecta. PMID- 26873943 TI - Do Self-Management Interventions Work in Patients With Heart Failure? An Individual Patient Data Meta-Analysis. AB - BACKGROUND: Self-management interventions are widely implemented in the care for patients with heart failure (HF). However, trials show inconsistent results, and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in patients with HF and whether subgroups of patients respond differently. METHODS AND RESULTS: A systematic literature search identified randomized trials of self-management interventions. Data from 20 studies, representing 5624 patients, were included and analyzed with the use of mixed effects models and Cox proportional-hazard models, including interaction terms. Self-management interventions reduced the risk of time to the combined end point of HF-related hospitalization or all-cause death (hazard ratio, 0.80; 95% confidence interval [CI], 0.71-0.89), time to HF-related hospitalization (hazard ratio, 0.80; 95% CI, 0.69-0.92), and improved 12-month HF-related quality of life (standardized mean difference, 0.15; 95% CI, 0.00-0.30). Subgroup analysis revealed a protective effect of self-management on the number of HF-related hospital days in patients <65 years of age (mean, 0.70 versus 5.35 days; interaction P=0.03). Patients without depression did not show an effect of self management on survival (hazard ratio for all-cause mortality, 0.86; 95% CI, 0.69 1.06), whereas in patients with moderate/severe depression, self-management reduced survival (hazard ratio, 1.39; 95% CI, 1.06-1.83, interaction P=0.01). CONCLUSIONS: This study shows that self-management interventions had a beneficial effect on time to HF-related hospitalization or all-cause death and HF-related hospitalization alone and elicited a small increase in HF-related quality of life. The findings do not endorse limiting self-management interventions to subgroups of patients with HF, but increased mortality in depressed patients warrants caution in applying self-management strategies in these patients. PMID- 26873946 TI - Breathlessness in an ex-miner: an unusual consideration. PMID- 26873944 TI - Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. AB - BACKGROUND: Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) >=25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. METHODS AND RESULTS: We analyzed retrospectively all US veterans undergoing right heart catheterization (2007-2012) in the Veterans Affairs healthcare system (n=21,727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004-1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (<=18 mm Hg; n=4,207); (2) borderline PH (19-24 mm Hg; n=5,030); and (3) PH (>=25 mm Hg; n=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12-1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96-2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01-1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09-1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance >=3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. CONCLUSIONS: These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH. PMID- 26873947 TI - Challenges in reproducing results from publicly available data: an example of sexual orientation and cardiovascular disease risk. AB - BACKGROUND: Replication is a vital part of the research process and has recently received considerable attention. Analyses using publicly available data should, if adequately described, be reproducible without assistance from the original investigators. Using data from the US National Health and Nutrition Examination Survey (NHANES), a recent study reported a statistically significant difference in cardiovascular disease risk comparing subgroups of sexual minority men. We attempted to reproduce these findings and assessed whether the results were robust to alternative analytic strategies and assumptions. METHODS: We used the exclusion criteria and coding strategy described in the original paper to construct our analytical data set. Sampling weights were constructed in accordance with NHANES analytical guidelines. We estimated crude and covariate adjusted associations between sexual orientation and vascular age using the regression models specified in the original report. We also conducted a series of sensitivity analyses to improve on the original findings. RESULTS: Our replication attempt was partially successful: we replicated the general trends reported in the original analysis, but not identical effect estimates. Importantly, we identified a potential misapplication of the Framingham Risk Score; correcting for this increased the probability that the reported null hypothesis test was a type I error. CONCLUSIONS: This paper supports the recent calls for greater transparency and improved reporting in research. Even with a publicly available and well-documented data source, we were unable to exactly replicate another study's original findings. Our sensitivity analyses revealed key issues in the original analysis and demonstrate the scientific importance of research replication. PMID- 26873948 TI - The impact of SASA!, a community mobilisation intervention, on women's experiences of intimate partner violence: secondary findings from a cluster randomised trial in Kampala, Uganda. AB - BACKGROUND: Intimate partner violence (IPV) is a global public health and human rights concern, though there is limited evidence on how to prevent it. This secondary analysis of data from the SASA! Study assesses the potential of a community mobilisation IPV prevention intervention to reduce overall prevalence of IPV, new onset of abuse (primary prevention) and continuation of prior abuse (secondary prevention). METHODS: A pair-matched cluster randomised controlled trial was conducted in 8 communities (4 intervention, 4 control) in Kampala, Uganda (2007-2012). Cross-sectional surveys of community members, 18-49 years old, were undertaken at baseline (n=1583) and 4 years postintervention implementation (n=2532). Outcomes relate to women's past year experiences of physical and sexual IPV, emotional aggression, controlling behaviours and fear of partner. An adjusted cluster-level intention-to-treat analysis compared outcomes in intervention and control communities at follow-up. RESULTS: At follow-up, all types of IPV (including severe forms of each) were lower in intervention communities compared with control communities. SASA! was associated with lower onset of abuse and lower continuation of prior abuse. Statistically significant effects were observed for continued physical IPV (adjusted risk ratio 0.42, 95% CI 0.18 to 0.96); continued sexual IPV (0.68, 0.53 to 0.87); continued emotional aggression (0.68, 0.52 to 0.89); continued fear of partner (0.67, 0.51 to 0.89); and new onset of controlling behaviours (0.38, 0.23 to 0.62). CONCLUSIONS: Community mobilisation is an effective means for both primary and secondary prevention of IPV. Further support should be given to the replication and scale up of SASA! and other similar interventions. TRIAL REGISTRATION NUMBER: NCT00790959. PMID- 26873949 TI - Estimating the burden of heat illness in England during the 2013 summer heatwave using syndromic surveillance. AB - BACKGROUND: The burden of heat illness on health systems is not well described in the UK. Although the UK generally experiences mild summers, the frequency and intensity of hot weather is likely to increase due to climate change, particularly in Southern England. We investigated the impact of the moderate heatwave in 2013 on primary care and emergency department (ED) visits using syndromic surveillance data in England. METHODS: General practitioner in hours (GPIH), GP out of hours (GPOOH) and ED syndromic surveillance systems were used to monitor the health impact of heat/sun stroke symptoms (heat illness). Data were stratified by age group and compared between heatwave and non-heatwave years. Incidence rate ratios were calculated for GPIH heat illness consultations. RESULTS: GP consultations and ED attendances for heat illness increased during the heatwave period; GPIH consultations increased across all age groups, but the highest rates were in school children and those aged >=75 years, with the latter persisting beyond the end of the heatwave. Extrapolating to the English population, we estimated that the number of GPIH consultations for heat illness during the whole summer (May to September) 2013 was 1166 (95% CI 1064 to 1268). This was double the rate observed during non-heatwave years. CONCLUSIONS: These findings support the monitoring of heat illness (symptoms of heat/sun stroke) as part of the Heatwave Plan for England, but also suggest that specifically monitoring heat illness in children, especially those of school age, would provide additional early warning of, and situation awareness during heatwaves. PMID- 26873950 TI - Dive characteristics can predict foraging success in Australian fur seals (Arctocephalus pusillus doriferus) as validated by animal-borne video. AB - Dive characteristics and dive shape are often used to infer foraging success in pinnipeds. However, these inferences have not been directly validated in the field with video, and it remains unclear if this method can be applied to benthic foraging animals. This study assessed the ability of dive characteristics from time-depth recorders (TDR) to predict attempted prey capture events (APC) that were directly observed on animal-borne video in Australian fur seals (Arctocephalus pusillus doriferus, n=11). The most parsimonious model predicting the probability of a dive with >=1 APC on video included only descent rate as a predictor variable. The majority (94%) of the 389 total APC were successful, and the majority of the dives (68%) contained at least one successful APC. The best model predicting these successful dives included descent rate as a predictor. Comparisons of the TDR model predictions to video yielded a maximum accuracy of 77.5% in classifying dives as either APC or non-APC or 77.1% in classifying dives as successful verses unsuccessful. Foraging intensity, measured as either total APC per dive or total successful APC per dive, was best predicted by bottom duration and ascent rate. The accuracy in predicting total APC per dive varied based on the number of APC per dive with maximum accuracy occurring at 1 APC for both total (54%) and only successful APC (52%). Results from this study linking verified foraging dives to dive characteristics potentially opens the door to decades of historical TDR datasets across several otariid species. PMID- 26873951 TI - Phylogenetic analysis and tissue distribution of elasmobranch glucose transporters and their response to feeding. AB - Elasmobranch diets consist of high quantities of protein and lipids, but very low levels of carbohydrates including glucose. Reflecting this diet, most tissues use lipids and ketone bodies as their main metabolic fuel. However, the rectal gland has been shown to be dependent on glucose as a fuel, so we hypothesized that glucose transporters (GLUTs) would be present and upregulated in the gland during times of activation (e.g. following a meal). In this study, we searched for and identified putative class I GLUTs in three elasmobranchs and a holocephalan using transcriptomes, and used these to reconstruct a Bayesian phylogeny. We determined that each of the four species possessed three of the four class I GLUT sequences, but the identities of the isoforms present in each species differed between the elasmobranchs (GLUT1, 3 and 4) and the holocephalan (GLUT1, 2 and 3). We then used qPCR to measure mRNA levels of these GLUTs in the rectal gland, liver, intestine, and muscle of fed and starved spiny dogfish (Squalus suckleyi). The rectal gland data showed higher mRNA levels of GLUT4 in the starved relative to the fed fish. In the muscle, both GLUT1 and 4 were significantly elevated at 24 h post-feeding, as was the case for GLUT4 in the liver. In the intestine on the other hand, GLUT4 was significantly elevated by 6 h post-feeding, remaining elevated through 48 h. We suggest that GLUT4 has taken on the role of GLUT2 in elasmobranchs as the expression patterns observed in the liver and intestine are representative of GLUT2 in other vertebrates. PMID- 26873952 TI - Changes in cell shape are correlated with metastatic potential in murine and human osteosarcomas. AB - Metastatic cancer cells for many cancers are known to have altered cytoskeletal properties, in particular to be more deformable and contractile. Consequently, shape characteristics of more metastatic cancer cells may be expected to have diverged from those of their parental cells. To examine this hypothesis we study shape characteristics of paired osteosarcoma cell lines, each consisting of a less metastatic parental line and a more metastatic line, derived from the former by in vivo selection. Two-dimensional images of four pairs of lines were processed. Statistical analysis of morphometric characteristics shows that shape characteristics of the metastatic cell line are partly overlapping and partly diverged from the parental line. Significantly, the shape changes fall into two categories, with three paired cell lines displaying a more mesenchymal-like morphology, while the fourth displaying a change towards a more rounded morphology. A neural network algorithm could distinguish between samples of the less metastatic cells from the more metastatic cells with near perfect accuracy. Thus, subtle changes in shape carry information about the genetic changes that lead to invasiveness and metastasis of osteosarcoma cancer cells. PMID- 26873955 TI - Comment: Is 3,4-DAP a new option in treating MuSK MG? PMID- 26873953 TI - Gene array analysis of neural crest cells identifies transcription factors necessary for direct conversion of embryonic fibroblasts into neural crest cells. AB - Neural crest cells (NC cells) are multipotent cells that emerge from the edge of the neural folds and migrate throughout the developing embryo. Although the gene regulatory network for generation of NC cells has been elucidated in detail, it has not been revealed which of the factors in the network are pivotal to directing NC identity. In this study we analyzed the gene expression profile of a pure NC subpopulation isolated from Sox10-IRES-Venus mice and investigated whether these genes played a key role in the direct conversion of Sox10-IRES Venus mouse embryonic fibroblasts (MEFs) into NC cells. The comparative molecular profiles of NC cells and neural tube cells in 9.5-day embryos revealed genes including transcription factors selectively expressed in developing trunk NC cells. Among 25 NC cell-specific transcription factor genes tested, SOX10 and SOX9 were capable of converting MEFs into SOX10-positive (SOX10+) cells. The SOX10+ cells were then shown to differentiate into neurons, glial cells, smooth muscle cells, adipocytes and osteoblasts. These SOX10+ cells also showed limited self-renewal ability, suggesting that SOX10 and SOX9 directly converted MEFs into NC cells. Conversely, the remaining transcription factors, including well-known NC cell specifiers, were unable to convert MEFs into SOX10+ NC cells. These results suggest that SOX10 and SOX9 are the key factors necessary for the direct conversion of MEFs into NC cells. PMID- 26873954 TI - Cost-effectiveness of endovascular thrombectomy in patients with acute ischemic stroke. AB - OBJECTIVE: To evaluate the cost-effectiveness of adding endovascular thrombectomy to standard care in patients with acute ischemic stroke. METHODS: The cost effectiveness analysis of endovascular thrombectomy in patients with acute ischemic stroke was based on a decision-analytic Markov model. Primary outcomes from ESCAPE, Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA), Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT), and Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke (SWIFT PRIME) along with data from published studies and registries were used in this analysis. We used a health care payer perspective and a lifelong time horizon to estimate costs and effects. RESULTS: The model showed that adding thrombectomy with stent retrievers to guideline-based care (including IV thrombolysis) resulted in a gain of 0.40 life-years and 0.99 quality-adjusted life-years along with a cost savings of approximately $221 per patient. The sensitivity analysis showed that the results were not sensitive to changes in uncertain parameters or assumptions. CONCLUSIONS: Adding endovascular treatment to standard care resulted in substantial clinical benefits at low costs. The results were consistent throughout irrespective of whether data from ESCAPE, EXTEND-IA, MR CLEAN, REVASCAT, or SWIFT PRIME were used in this model. PMID- 26873956 TI - Fulminant corticobasal degeneration: Agrypnia excitata in corticobasal syndrome. PMID- 26873957 TI - 3,4-Diaminopyridine may improve myasthenia gravis with MuSK antibodies. PMID- 26873958 TI - Cutaneous sensory and autonomic denervation in CADASIL. AB - OBJECTIVE: To assess the involvement of the peripheral nervous system in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) by means of immunofluorescence and confocal analysis of punch skin biopsies. METHODS: We recruited 14 unrelated patients with CADASIL (M/F = 9/5; age 53.9 +/- 10.5 years) and 52 healthy controls (M/F = 31/21; age 53.8 +/- 9.8). Patients underwent clinical and neuroradiologic assessment. Three-millimeter punch skin biopsies were taken from the fingertip, the thigh, and the distal leg and processed using indirect immunofluorescence and a panel of primary antibodies to mark vessels and sensory and autonomic nerve fibers. Intraepidermal nerve fibers (IENF), Meissner corpuscles (MC), and sudomotor, vasomotor, and pilomotor nerves were assessed using confocal microscopy. RESULTS: In patients, compared to controls, we found a severe loss of IENF at the distal leg (p < 0.01), at the thigh (p < 0.01), and at the fingertip (p < 0.01) with a non-length-dependent pattern and a loss of MC (p < 0.01). A severe sudomotor, vasomotor, and pilomotor nerve fiber loss was found by semiquantitative evaluation. Along with nerve loss, a severe derangement of the vascular bed was observed. In our patient population, sensory and autonomic denervation did not correlate with age, sex, type of mutation, or MRI involvement. CONCLUSIONS: We found an involvement of the peripheral nervous system in patients with CADASIL through the assessment of cutaneous somatic and autonomic nerves. The neurovascular derangement observed in the skin may reflect, although to a lesser extent, what happens in the CNS. PMID- 26873959 TI - Identification of Niclosamide as a Novel Anticancer Agent for Adrenocortical Carcinoma. AB - PURPOSE: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer, and no current effective therapy is available for locally advanced and metastatic ACC. Drug repurposing is an emerging approach for identifying new indications for existing drugs, especially for rare cancers such as ACC. The objective of this study was to use quantitative high-throughput screening to identify agents with antineoplastic activity against ACC. EXPERIMENTAL DESIGN: A screening of 4,292 compounds was performed on three ACC cell lines: BD140A, SW-13, and NCI-H295R. RESULTS: Twenty-one active compounds were identified, with an efficacy of >80% in all three cell lines. Of these, niclosamide showed higher efficacy and lower IC50 than established anti-ACC drugs. We then validated niclosamide-inhibited cellular proliferation in all three ACC cell lines. Next, we investigated the mechanism by which niclosamide inhibited ACC cell proliferation, and found that it induced caspase-dependent apoptosis and G1 cell-cycle arrest. Niclosamide also decreased cellular migration and reduced the level of mediators of epithelial-to mesenchymal transition, such as N-cadherin and vimentin. Furthermore, niclosamide treatment resulted in decreased expression of beta-catenin. We also evaluated the effect of niclosamide on energy metabolism in ACC cell lines and found it resulted in mitochondrial uncoupling. Niclosamide treatment inhibited ACC tumor growth with no observed toxicity in mice in vivo CONCLUSIONS: Our findings suggest that niclosamide has anti-ACC activity through its inhibition of multiple altered cellular pathways and cellular metabolism in ACC. Our results provide a preclinical rationale for evaluating niclosamide therapy in a clinical trial for ACC. Clin Cancer Res; 22(14); 3458-66. (c)2016 AACR. PMID- 26873961 TI - Inference for the existence of hormetic dose-response relationships in toxicology studies. AB - In toxicology studies hormesis refers to a dose-response relationship with a stimulatory response at low doses and an inhibitory response at high doses. In this manuscript, we particularly focus on a J-shaped dose-response relationship for binary cancer responses. We propose and examine two new flexible models for testing the hypothesis of hormesis in a Bayesian framework. The first model is parametric and enhances the flexibility of modeling a hormetic zone by using a non-linear predictor in a multistage model. The second model is non-parametric and allows multiple model specifications, weighting the contribution of each model via Bayesian model averaging (BMA). Simulation studies show that the non parametric modeling approach with BMA provides robust sensitivity and specificity for detecting hormesis relative to the parametric approach, regardless of the shape of a hormetic zone. PMID- 26873960 TI - Vaccination with Irradiated Autologous Tumor Cells Mixed with Irradiated GM-K562 Cells Stimulates Antitumor Immunity and T Lymphocyte Activation in Patients with Recurrent Malignant Glioma. AB - PURPOSE: Recurrent malignant glioma carries a dismal prognosis, and novel therapies are needed. We examined the feasibility and safety of vaccination with irradiated autologous glioma cells mixed with irradiated GM-K562 cells in patients undergoing craniotomy for recurrent malignant glioma. EXPERIMENTAL DESIGN: We initiated a phase I study examining the safety of 2 doses of GM-K562 cells mixed with autologous cells. Primary endpoints were feasibility and safety. Feasibility was defined as the ability for 60% of enrolled subjects to initiate vaccination. Dose-limiting toxicity was assessed via a 3+3 dose-escalation format, examining irradiated tumor cells mixed with 5 * 10(6) GM-K562 cells or 1 * 10(7) GM-K562 cells. Eligibility required a priori indication for resection of a recurrent high-grade glioma. We measured biological activity by measuring delayed type hypersensitivity (DTH) responses, humoral immunity against tumor associated antigens, and T-lymphocyte activation. RESULTS: Eleven patients were enrolled. Sufficient numbers of autologous tumor cells were harvested in 10 patients, all of whom went on to receive vaccine. There were no dose-limiting toxicities. Vaccination strengthened DTH responses to irradiated autologous tumor cells in most patients, and vigorous humoral responses to tumor-associated angiogenic cytokines were seen as well. T-lymphocyte activation was seen with significantly increased expression of CTLA-4, PD-1, 4-1BB, and OX40 by CD4(+) cells and PD-1 and 4-1BB by CD8(+) cells. Activation was coupled with vaccine associated increase in the frequency of regulatory CD4(+) T lymphocytes. CONCLUSIONS: Vaccination with irradiated autologous tumor cells mixed with GM K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. Clin Cancer Res; 22(12); 2885-96. (c)2016 AACR. PMID- 26873962 TI - Transcranial Electrical Stimulation: What We Know and Do Not Know About Mechanisms. AB - In recent years, there has been remarkable progress in the understanding and practical use of transcranial electrical stimulation (tES) techniques. Nevertheless, to date, this experimental effort has not been accompanied by substantial reflections on the models and mechanisms that could explain the stimulation effects. Given these premises, the aim of this article is to provide an updated picture of what we know about the theoretical models of tES that have been proposed to date, contextualized in a more specific and unitary framework. We demonstrate that these models can explain the tES behavioral effects as distributed along a continuum from stimulation dependent to network activity dependent. In this framework, we also propose that stochastic resonance is a useful mechanism to explain the general online neuromodulation effects of tES. Moreover, we highlight the aspects that should be considered in future research. We emphasize that tES is not an "easy-to-use" technique; however, it may represent a very fruitful approach if applied within rigorous protocols, with deep knowledge of both the behavioral and cognitive aspects and the more recent advances in the application of stimulation. PMID- 26873963 TI - GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension. AB - The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na(+)) or high-salt diet (HS; 4% Na(+)) for 10 wk, which significantly increased systolic blood pressure (149 +/- 5 vs. 224 +/- 8 mmHg;P< 0.001). Treatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 +/- 4 mmHg;P> 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine (P> 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to lumen ratio (NS: 0.43; HS+veh: 0.89; HS+G-1: 0.61;P< 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm(2);P< 0.001) and lipid peroxidation (0.11 vs. 0.51 mm(2);P< 0.01), both of which were reduced by G-1 (0.20 mm(2)and 0.23 mm(2); both P< 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage. PMID- 26873964 TI - Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion. AB - Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol 308: H894 H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventional C3 knockout (C3(-/ )) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that cardiac Sirt1 regulates the local complement system during CR. PMID- 26873965 TI - Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats. AB - Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal (n= 10) and MCT PH rats (n= 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance (ZC) and peripheral pulmonary resistance (RP) (ZC: 0.121 +/- 0.039 vs. 0.053 +/- 0.017 mmHg.min.ml( 1), P< 0.001; RP: 0.581 +/- 0.334 vs. 0.252 +/- 0.105 mmHg.min.ml(-1), P= 0.013) and lower pulmonary artery compliance (CP) (0.242 +/- 0.131 vs. 0.700 +/- 0.186 ml/mmHg, P< 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 +/- 0.020 without pump activation to 0.019 +/- 0.007 with pump activation,P< 0.001; phase: 0.085 +/- 0.028 to 0.043 +/- 0.012 radians,P< 0.001). In conclusion, MCT PH increases ZC and RP and decreases CP Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH. PMID- 26873968 TI - Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats. AB - Bacterial infections increase risk for pregnancy complications, such as preeclampsia and preterm birth. Unmethylated CpG DNA sequences are present in bacterial DNA and have immunostimulatory effects. Maternal exposure to CpG DNA induces fetal demise and craniofacial malformations; however, the effects of CpG DNA on maternal cardiovascular health have not been examined. We tested the hypothesis that exposure to synthetic CpG oligonucleotides (ODNs) during gestation would increase blood pressure and cause vascular dysfunction in pregnant rats. Pregnant and nonpregnant female rats were treated with CpG ODN (ODN 2395) or saline (Veh) starting on gestational day 14or corresponding day for the nonpregnant groups. Exposure to CpG ODN increased systolic blood pressure in pregnant (Veh: 121 +/- 2 mmHg vs. ODN 2395: 134 +/- 2 mmHg,P< 0.05) but not in nonpregnant rats (Veh: 111 +/- 2 mmHg vs. ODN 2395: 108 +/- 5 mmHg,P> 0.05). Mesenteric resistance arteries from pregnant CpG ODN-treated rats had increased contractile responses to U46619 [thromboxane A2(TxA2) mimetic] compared with arteries from vehicle-treated rats [Emax(%KCl), Veh: 87 +/- 4 vs. ODN 2395: 104 +/- 4,P< 0.05]. Nitric oxide synthase (NOS) inhibition increased contractile responses to U46619, and CpG ODN treatment abolished this effect in arteries from pregnant ODN 2395-treated rats. CpG ODN potentiated the involvement of cyclooxygenase (COX) to U46619-induced contractions. In conclusion, exposure to CpG ODN during gestation induces maternal hypertension, augments resistance artery contraction, increases the involvement of COX-dependent mechanisms and reduces the contribution of NOS-dependent mechanisms to TxA2-induced contractions in mesenteric resistance arteries. PMID- 26873966 TI - Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin induced cardiomyopathy in mice. AB - Doxorubicin (Doxo) is a chemotherapeutic drug widely used to treat variety of cancers. One of the most serious side effects of Doxo is its dose-dependent and delayed toxicity to the heart. Doxo is known to induce cardiac mitochondrial damage. Recently, the mitochondrial sirtuin SIRT3 has been shown to protect mitochondria from oxidative stress. Here we show that overexpression of SIRT3 protects the heart from toxicity of Doxo by preventing the drug-induced mitochondrial DNA (mtDNA) damage. Doxo treatment caused depletion of Sirt3 levels both in primary cultures of cardiomyocytes and in mouse hearts, which led to massive acetylation of mitochondrial proteins. Doxo-induced toxicity to cardiomyocytes was associated with increased reactive oxygen species (ROS) production, mitochondrial fragmentation, and cell death. Overexpression of SIRT3 helped to attenuate Doxo-induced ROS levels and cardiomyocyte death. Sirt3 knockout (Sirt3.KO) mice could not endure the full dose of Doxo treatment, developed exacerbated cardiac hypertrophy, and died during the course of treatment, whereas Sirt3 transgenic (Sirt3.tg) mice were protected against Doxo induced cardiotoxicity. Along with Sirt3, we also observed a concomitant decrease in levels of oxoguanine-DNA glycosylase-1 (OGG1), a major DNA glycosylase that hydrolyzes oxidized-guanine (8-oxo-dG) to guanine. Depletion of OGG1 levels was associated with increased mtDNA damage. Sirt3.KO mice and Doxo-treated mice showed increased 8-oxo-dG adducts in DNA and corresponding increase in mtDNA damage, whereas, 8-oxo-dG adducts and mtDNA damage were markedly reduced in Sirt3 overexpressing transgenic mice hearts. These results thus demonstrated that Sirt3 activation protects the heart from Doxo-induced cardiotoxicity by maintaining OGG1 levels and protecting mitochondria from DNA damage. PMID- 26873967 TI - Cardiac angiotensin-(1-12) expression and systemic hypertension in rats expressing the human angiotensinogen gene. AB - Angiotensin-(1-12) [ANG-(1-12)] is processed into ANG II by chymase in rodent and human heart tissue. Differences in the amino acid sequence of rat and human ANG (1-12) render the human angiotensinogen (hAGT) protein refractory to cleavage by renin. We used transgenic rats harboring the hAGT gene [TGR(hAGT)L1623] to assess the non-renin-dependent effects of increased hAGT expression on heart function and arterial pressure. Compared with Sprague-Dawley (SD) control rats (n= 11), male homozygous TGR(hAGT)L1623 (n= 9) demonstrated sustained daytime and nighttime hypertension associated with no changes in heart rate but increased heart rate lability. Increased heart weight/tibial length ratio and echocardiographic indexes of cardiac hypertrophy were associated with modest reduction of systolic function in hAGT rats. Robust human ANG-(1-12) immunofluorescence within myocytes of TGR(hAGT)L1623 rats was associated with a fourfold increase in cardiac ANG II content. Chymase enzymatic activity, using the rat or human ANG-(1-12) as a substrate, was not different in the cardiac tissue of SD and hAGT rats. Since both cardiac angiotensin-converting enzyme (ACE) and ACE2 activities were not different among the two strains, the changes in cardiac structure and function, blood pressure, and left ventricular ANG II content might be a product of an increased cardiac expression of ANG II generated through a non-renin-dependent mechanism. The data also underscore the existence in the rat of alternate enzymes capable of acting on hAGT protein. Homozygous transgenic rats expressing the hAGT gene represent a novel tool to investigate the contribution of human relevant renin-independent cardiac ANG II formation and function. PMID- 26873969 TI - BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy. AB - Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis. PMID- 26873970 TI - Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells. AB - Voltage-gated L-type Ca(2+) current (ICa,L) induces contraction of arterial smooth muscle cells (ASMCs), and ICa,L is increased by H2O2 in ASMCs. Superoxide released from the mitochondrial respiratory chain (MRC) is dismutated to H2O2 We studied whether superoxide per se acutely modulates ICa,L in ASMCs using cultured A7r5 cells derived from rat aorta. Rotenone is a toxin that inhibits complex I of the MRC and increases mitochondrial superoxide release. The superoxide content of mitochondria was estimated using mitochondrial-specific MitoSOX and HPLC methods, and was shown to be increased by a brief exposure to 10 MUM rotenone. ICa,L was recorded with 5 mM BAPTA in the pipette solution. Rotenone administration (10 nM to 10 MUM) resulted in a greater ICa,L increase in a dose-dependent manner to a maximum of 22.1% at 10 MUM for 1 min, which gradually decreased to 9% after 5 min. The rotenone-induced ICa,L increase was associated with a shift in the current-voltage relationship (I-V) to a hyperpolarizing direction. DTT administration resulted in a 17.9% increase in ICa,L without a negative shift in I-V, and rotenone produced an additional increase with a shift. H2O2 (0.3 mM) inhibited ICa,L by 13%, and additional rotenone induced an increase with a negative shift. Sustained treatment with Tempol (4-hydroxy tempo) led to a significant ICa,L increase but it inhibited the rotenone-induced increase. Staurosporine, a broad-spectrum protein kinase inhibitor, partially inhibited ICa,L and completely suppressed the rotenone-induced increase. Superoxide released from mitochondria affected protein kinases and resulted in stronger ICa,L preceding its dismutation to H2O2 The removal of nitric oxide is a likely mechanism for the increase in ICa,L. PMID- 26873971 TI - Muscle metaboreflex and cerebral blood flow regulation in humans: implications for exercise with blood flow restriction. AB - We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 +/- 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ~120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2 ), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2 was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2 clamp trial). In the control trial, leg cycling with BFR decreased PetCO2 (Delta-4.8 +/- 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvm were unchanged and MCACVCi decreased. However, in the PetCO2 clamp trial, leg cycling with BFR increased both MCAvm (Delta5.9 +/- 1.4 cm/s) and ICAQ (Delta20.0 +/- 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVC was unchanged. In the control trial, PEI decreased PetCO2 (Delta-7.0 +/- 1.3 mmHg vs. rest), MCAvm and MCACVCi, whereas ICAQ and ICACVC were unchanged. In contrast, in the PetCO2 clamp trial both ICAQ (Delta18.5 +/- 11.9 ml/min) and MCAvm (Delta8.8 +/- 2.0 cm/s) were elevated, while ICACVC and MCACVCi were unchanged. In conclusion, when hyperventilation-related decreases in PetCO2 are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow. PMID- 26873972 TI - Novel wave power analysis linking pressure-flow waves, wave potential, and the forward and backward components of hydraulic power. AB - Wave intensity analysis provides detailed insights into factors influencing hemodynamics. However, wave intensity is not a conserved quantity, so it is sensitive to diameter variations and is not distributed among branches of a junction. Moreover, the fundamental relation between waves and hydraulic power is unclear. We, therefore, propose an alternative to wave intensity called "wave power," calculated via incremental changes in pressure and flow (dPdQ) and a novel time-domain separation of hydraulic pressure power and kinetic power into forward and backward wave-related components (PiP+/-and PiQ+/-). Wave power has several useful properties:1) it is obtained directly from flow measurements, without requiring further calculation of velocity;2) it is a quasi-conserved quantity that may be used to study the relative distribution of waves at junctions; and3) it has the units of power (Watts). We also uncover a simple relationship between wave power and changes in PiP+/-and show that wave reflection reduces transmitted power. Absolute values of PiP+/-represent wave potential, a recently introduced concept that unifies steady and pulsatile aspects of hemodynamics. We show that wave potential represents the hydraulic energy potential stored in a compliant pressurized vessel, with spatial gradients producing waves that transfer this energy. These techniques and principles are verified numerically and also experimentally with pressure/flow measurements in all branches of a central bifurcation in sheep, under a wide range of hemodynamic conditions. The proposed "wave power analysis," encompassing wave power, wave potential, and wave separation of hydraulic power provides a potent time-domain approach for analyzing hemodynamics. PMID- 26873973 TI - The mitochondrial function of the cerebral vasculature in insulin-resistant Zucker obese rats. AB - Little is known about mitochondrial functioning in the cerebral vasculature during insulin resistance (IR). We examined mitochondrial respiration in isolated cerebral arteries of male Zucker obese (ZO) rats and phenotypically normal Zucker lean (ZL) rats using the Seahorse XFe24 analyzer. We investigated mitochondrial morphology in cerebral blood vessels as well as mitochondrial and nonmitochondrial protein expression levels in cerebral arteries and microvessels. We also measured reactive oxygen species (ROS) levels in cerebral microvessels. Under basal conditions, the mitochondrial respiration components (nonmitochondrial respiration, basal respiration, ATP production, proton leak, and spare respiratory capacity) showed similar levels among the ZL and ZO groups with the exception of maximal respiration, which was higher in the ZO group. We examined the role of nitric oxide by measuring mitochondrial respiration following inhibition of nitric oxide synthase with N(omega)-nitro-l-arginine methyl ester (l-NAME) and mitochondrial activation after administration of diazoxide (DZ). Both ZL and ZO groups showed similar responses to these stimuli with minor variations.l-NAME significantly increased the proton leak, and DZ decreased nonmitochondrial respiration in the ZL group. Other components were not affected. Mitochondrial morphology and distribution within vascular smooth muscle and endothelium as well as mitochondrial protein levels were similar in the arteries and microvessels of both groups. Endothelial nitric oxide synthase (eNOS) and ROS levels were increased in cerebral microvessels of the ZO. Our study suggests that mitochondrial function is not significantly altered in the cerebral vasculature of young ZO rats, but increased ROS production might be due to increased eNOS in the cerebral microcirculation during IR. PMID- 26873974 TI - Antenatal BAY 41-2272 reduces pulmonary hypertension in the rabbit model of congenital diaphragmatic hernia. AB - Infants with congenital diaphragmatic hernia (CDH) fail to adapt at birth because of persistent pulmonary hypertension (PH), a condition characterized by excessive muscularization and abnormal vasoreactivity of pulmonary vessels. Activation of soluble guanylate cyclase by BAY 41-2272 prevents pulmonary vascular remodeling in neonatal rats with hypoxia-induced PH. By analogy, we hypothesized that prenatal administration of BAY 41-2272 would improve features of PH in the rabbit CDH model. Rabbit fetuses with surgically induced CDH at day 23 of gestation were randomized at day 28 for an intratracheal injection of BAY 41-2272 or vehicle. After term delivery (day 31), lung mechanics, right ventricular pressure, and serum NH2-terminal-pro-brain natriuretic peptide (NT-proBNP) levels were measured. After euthanasia, lungs were processed for biological or histological analyses. Compared with untouched fetuses, the surgical creation of CDH reduced the lung-to-body weight ratio, increased mean terminal bronchial density, and impaired lung mechanics. Typical characteristics of PH were found in the hypoplastic lungs, including increased right ventricular pressure, higher serum NT-proBNP levels, thickened adventitial and medial layers of pulmonary arteries, reduced capillary density, and lower levels of endothelial nitric oxide synthase. A single antenatal instillation of BAY 41-2272 reduced mean right ventricular pressure and medial thickness of small resistive arteries in CDH fetuses. Capillary density, endothelial cell proliferation, and transcripts of endothelial nitric oxide synthase increased, whereas airway morphometry, lung growth, and mechanics remained unchanged. These results suggest that pharmacological activation of soluble guanylate cyclase may provide a new approach to the prenatal treatment of PH associated with CDH. PMID- 26873975 TI - Semi-Rolled Leaf2 modulates rice leaf rolling by regulating abaxial side cell differentiation. AB - Moderate leaf rolling maintains the erectness of leaves and minimizes the shadowing between leaves which is helpful to establish ideal plant architecture. Here, we describe asrl2(semi-rolled leaf2) rice mutant, which has incurved leaves due to the presence of defective sclerenchymatous cells on the abaxial side of the leaf and displays narrow leaves and reduced plant height. Map-based cloning revealed that SRL2 encodes a novel plant-specific protein of unknown biochemical function.SRL2 was mainly expressed in the vascular bundles of leaf blades, leaf sheaths, and roots, especially in their sclerenchymatous cells. The transcriptional activities of several leaf development-related YABBY genes were significantly altered in the srl2 mutant. Double mutant analysis suggested that SRL2 and SHALLOT-LIKE1(SLL1)/ROLLED LEAF9(RL9) function in distinct pathways that regulate abaxial-side leaf development. Hence, SRL2 plays an important role in regulating leaf development, particularly during sclerenchymatous cell differentiation. PMID- 26873976 TI - Natural variation in rosette size under salt stress conditions corresponds to developmental differences between Arabidopsis accessions and allelic variation in the LRR-KISS gene. AB - Natural variation among Arabidopsis accessions is an important genetic resource to identify mechanisms underlying plant development and stress tolerance. To evaluate the natural variation in salinity stress tolerance, two large-scale experiments were performed on two populations consisting of 160 Arabidopsis accessions each. Multiple traits, including projected rosette area, and fresh and dry weight were collected as an estimate for salinity tolerance. Our results reveal a correlation between rosette size under salt stress conditions and developmental differences between the accessions grown in control conditions, suggesting that in general larger plants were more salt tolerant. This correlation was less pronounced when plants were grown under severe salt stress conditions. Subsequent genome wide association study (GWAS) revealed associations with novel candidate genes for salinity tolerance such as LRR-KISS (At4g08850),flowering locus KH-domain containing protein and a DUF1639-containing protein Accessions with high LRR-KISS expression developed larger rosettes under salt stress conditions. Further characterization of allelic variation in candidate genes identified in this study will provide more insight into mechanisms of salt stress tolerance due to enhanced shoot growth. PMID- 26873977 TI - Fertilization Independent Endosperm genes repress NbGH3.6 and regulate the auxin level during shoot development in Nicotiana benthamiana. AB - The Fertilization Independent Endosperm (FIE) gene is required to restrict endosperm development without fertilization, and it represses flowering during embryo and seedling development in Arabidopsis thaliana However, the regulatory mechanism of the FIE gene in postembryonic shoot development is not well understood. Silencing of Nicotiana benthamiana homologues of the FIE gene, NbFIE1 and NbFIE2, resulted in the enhanced outgrowth of axillary buds and the impairment of secondary xylem differentiation. RNA sequencing analysis found that one of the auxin-responsive GRETCHEN HAGEN 3(GH3) family genes, NbGH3.6, was upregulated and maintained a high expression during the time course of silencing NbFIE genes. Chromatin immunoprecipiation (ChIP)-PCR results showed a lack of H3K27me3 marks on NbGH3.6 chromatin in NbFIE-silenced plants compared with negative control plants, indicating that NbGH3.6 was a direct target of NbFIE genes during postembryonic shoot development. Moreover, the free IAA content was reduced significantly in NbFIE-silenced plants, which might cause the enhanced outgrowth of axillary buds as well as impaired secondary xylem differentiation. These results clearly indicated that NbGH3.6 was a primary target of NbFIE genes during postembryonic shoot development, and NbFIE genes regulated axillary bud growth and secondary xylem formation through tuning endogenous auxin homeostasis, possibly by regulating the expression of the NbGH3.6 gene. PMID- 26873978 TI - Regulation of Arabidopsis thaliana seed dormancy and germination by 12-oxo phytodienoic acid. AB - We previously demonstrated that the oxylipin 12-oxo-phytodienoic acid (OPDA) acts along with abscisic acid to regulate seed germination in Arabidopsis thaliana, but the mechanistic details of this synergistic interaction remain to be elucidated. Here, we show that OPDA acts through the germination inhibition effects of abscisic acid, the abscisic acid-sensing ABI5 protein, and the gibberellin-sensing RGL2 DELLA protein. We further demonstrate that OPDA also acts through another dormancy-promoting factor, MOTHER-OF-FT-AND-TFL1 (MFT). Both abscisic acid and MFT positively feed back into the OPDA pathway by promoting its accumulation. These results confirm the central role of OPDA in regulating seed dormancy and germination in A. thaliana and underline the complexity of interactions between OPDA and other dormancy-promoting factors such as abscisic acid, RGL2, and MFT. PMID- 26873979 TI - The cotton MYB108 forms a positive feedback regulation loop with CML11 and participates in the defense response against Verticillium dahliae infection. AB - Accumulating evidence indicates that plant MYB transcription factors participate in defense against pathogen attack, but their regulatory targets and related signaling processes remain largely unknown. Here, we identified a defense-related MYB gene (GhMYB108) from upland cotton (Gossypium hirsutum) and characterized its functional mechanism. Expression of GhMYB108 in cotton plants was induced by Verticillium dahliae infection and responded to the application of defense signaling molecules, including salicylic acid, jasmonic acid, and ethylene. Knockdown of GhMYB108 expression led to increased susceptibility of cotton plants to V. dahliae, while ecotopic overexpression of GhMYB108 in Arabidopsis thaliana conferred enhanced tolerance to the pathogen. Further analysis demonstrated that GhMYB108 interacted with the calmodulin-like protein GhCML11, and the two proteins form a positive feedback loop to enhance the transcription of GhCML11 in a calcium-dependent manner. Verticillium dahliae infection stimulated Ca(2+) influx into the cytosol in cotton root cells, but this response was disrupted in both GhCML11-silenced plants and GhMYB108-silenced plants in which expression of several calcium signaling-related genes was down-regulated. Taken together, these results indicate that GhMYB108 acts as a positive regulator in defense against V. dahliae infection by interacting with GhCML11. Furthermore, the data also revealed the important roles and synergetic regulation of MYB transcription factor, Ca(2+), and calmodulin in plant immune responses. PMID- 26873980 TI - Rhizosheaths on wheat grown in acid soils: phosphorus acquisition efficiency and genetic control. AB - Rhizosheaths comprise soil bound to roots, and in wheat (Triticum aestivum L.) rhizosheath size correlates with root hair length. The aims of this study were to determine the effect that a large rhizosheath has on the phosphorus (P) acquisition by wheat and to investigate the genetic control of rhizosheath size in wheat grown on acid soil.Near-isogenic wheat lines differing in rhizosheath size were evaluated on two acid soils. The soils were fertilized with mineral nutrients and included treatments with either low or high P. The same soils were treated with CaCO3 to raise the pH and detoxify Al(3+) Genotypic differences in rhizosheath size were apparent only when soil pH was low and Al(3+) was present. On acid soils, a large rhizosheath increased shoot biomass compared with a small rhizosheath regardless of P supply. At low P supply, increased shoot biomass could be attributed to a greater uptake of soil P, but at high P supply the increased biomass was due to some other factor. Generation means analysis indicated that rhizosheath size on acid soil was controlled by multiple, additive loci. Subsequently, a quantitative trait loci (QTL) analysis of an F6 population of recombinant inbred lines identified five major loci contributing to the phenotype together accounting for over 60% of the total genetic variance. One locus on chromosome 1D accounted for 34% of the genotypic variation. Genetic control of rhizosheath size appears to be relatively simple and markers based on the QTL provide valuable tools for marker assisted breeding. PMID- 26873981 TI - Superoxide Dismutase 2 Genetic Variation as a Susceptibility Risk Factor for Alcoholic Cirrhosis. AB - AIMS: Superoxide dismutase 2 (SOD2) is an important antioxidant phase 2 enzyme. The associations of SOD2 genetic variation and the risk of advanced alcoholic liver diseases are still debatable. We aimed to investigate the association of the main SOD2 genetic variant (47T>C) and the susceptibility to alcoholic cirrhosis. METHODS: A total of 80 patients with alcoholic cirrhosis (AC), 80 patients with alcoholic non-cirrhosis (ANC), 80 with viral hepatitis B-related cirrhosis (VC), and 165 healthy controls (HC) were enrolled into this study. A polymerase chain reaction was used to genotype their SOD2 47T>C (rs4880). RESULTS: There was no statistical difference in the frequency distribution of the three SOD2 47T>C genotypes among groups. However, if individuals with C variant were grouped together, the AC group had higher frequency of SOD2 C/C or C/T genotype than ANC, VC and HC groups had (38.7% vs. 21.3%, 26.3% and 21.8%, respectively, P = 0.010). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of AC (adjusted OR: 2.79 and 3.50, respectively, P < 0.03, compared with ANC and HC groups). In contrast, there was no significant difference of SOD2 genetic variation between VC and HC groups. CONCLUSIONS: Anti-oxidative enzyme SOD2 47T>C genetic variant may increase the susceptibility to AC. This suggests that oxidative stress plays a role in the development of AC. PMID- 26873982 TI - Prevalence and Trends in Alcohol Dependence and Alcohol Use Disorders in Japanese Adults; Results from Periodical Nationwide Surveys. AB - AIMS: Nationwide surveys to clarify the characteristics and trends of the drinking behavior of Japanese adults were carried out in 2003, 2008, and 2013. METHODS: These were periodical cross-sectional surveys. Subjects were chosen through a stratified two-stage random sampling method. The surveys included drinking frequency and amount, ICD-10 alcoholism diagnostic standards, questionnaire for the determination of harmful alcohol use ( AUDIT: Alcohol Use Disorders Identification Test). In 2003, the surveys obtained responses from 2547 people (73% response rate); in 2008, 4123 people (55% response rate); and in 2013, 4153 people (59% response rate). RESULTS: The proportion of lifetime experience of alcohol dependence diagnosed by ICD-10 was 1.9% for male and 0.2% for female, and the estimated number of patients was 1.07 million. The declining trends were observed in the percentage of daily drinkers and the amount of alcohol consumed per week for male. The lowering of the age for consuming their first alcoholic drink and their first drunken experience was observed among female. The gender difference of prevalence of problem drinking is getting smaller. The binge drinking and heavy episodic drinking were observed especially younger generation. The only small proportion of patients with alcohol dependence had received specialized medical care, whereas the many of these visited medical institutions and health screening. CONCLUSIONS: The survey observed many hidden alcoholic patients, and showed the possibility that the healthcare facilities and health screening became the place of screening and intervention for alcohol dependence. PMID- 26873983 TI - Moving the integration of palliative care from idea to practice. PMID- 26873984 TI - What are the views of hospital-based generalist palliative care professionals on what facilitates or hinders collaboration with in-patient specialist palliative care teams? A systematically constructed narrative synthesis. AB - BACKGROUND: Hospital-based specialist palliative care services are common, yet existing evidence of inpatient generalist providers' perceptions of collaborating with hospital-based specialist palliative care teams has never been systematically assessed. AIM: To assess the existing evidence of inpatient generalist palliative care providers' perceptions of what facilitates or hinders collaboration with hospital-based specialist palliative care teams. DESIGN: Narrative literature synthesis with systematically constructed search. DATA SOURCES: PsycINFO, PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature and ProQuest Social Services databases were searched up to December 2014. Individual journal, citation and reference searching were also conducted. Papers with the views of generalist inpatient professional caregivers who utilised hospital-based specialist palliative care team services were included in the narrative synthesis. Hawker's criteria were used to assess the quality of the included studies. RESULTS: Studies included (n = 23) represented a variety of inpatient generalist palliative care professionals' experiences of collaborating with specialist palliative care. Effective collaboration is experienced by many generalist professionals. Five themes were identified as improving or decreasing effective collaboration: model of care (integrated vs linear), professional onus, expertise and trust, skill building versus deskilling and specialist palliative care operations. Collaboration is fostered when specialist palliative care teams practice proactive communication, role negotiation and shared problem-solving and recognise generalists' expertise. CONCLUSION: Fuller integration of specialist palliative care services, timely sharing of information and mutual respect increase generalists' perceptions of effective collaboration. Further research is needed regarding the experiences of non-physician and non-nursing professionals as their views were either not included or not explicitly reported. PMID- 26873985 TI - Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer. AB - Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. PMID- 26873986 TI - Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication. AB - HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1 producing cells in chronic asymptomatic HIV-1 infection. PMID- 26873988 TI - FVB/N Mice Spontaneously Heal Ulcerative Lesions Induced by Mycobacterium ulcerans and Switch M. ulcerans into a Low Mycolactone Producer. AB - Buruli ulcer, a debilitating disease, is caused by Mycobacterium ulcerans. The incidence of this neglected tropical disease is steadily increasing. As a rule, without treatment, skin ulcers occur and a lengthy healing process may be observed associated with severe functional disabilities. Mouse models are already available to study establishment of lesions or evaluation of therapy but a lack of a suitable animal model, mimicking all clinical stages, in particular the healing process, remains an obstacle to understand the pathophysiology of M. ulcerans infection. M. ulcerans was s.c. inoculated in three consanguine mouse strains, that is, BALB/c and C57BL/6, classically used to study mycobacterial infection, and FVB/N. Strikingly, FVB/N mice, although as sensitive as all other mouse strains with respect to M. ulcerans infection, presented a spontaneous healing after the ulcerative phase despite stable bacterial load, and mycolactone toxin was not detected in the healed tissues. The spontaneous healing process was accompanied by an activation of the innate immune system. The adaptive response initiated by FVB/N mice was not involved in the healing process and did not confer protection against M. ulcerans. Our work highlights the importance of innate immune responses to control M. ulcerans infection. This in vivo model of M. ulcerans infection now paves the way for new avenues of research toward the elucidation of critical stages of this disease, such as the characterization of the regulation of mycolactone production, a better understanding of the pathophysiology of M. ulcerans infection, and the development of new therapeutic strategies. PMID- 26873987 TI - Rapid Evolution of the CD8+ TCR Repertoire in Neonatal Mice. AB - Currently, there is little consensus regarding the most appropriate animal model to study acute infection and the virus-specific CD8(+) T cell (CTL) responses in neonates. TCRbeta high-throughput sequencing in naive CTL of differently aged neonatal mice was performed, which demonstrated differential Vbeta family gene usage. Using an acute influenza infection model, we examined the TCR repertoire of the CTL response in neonatal and adult mice infected with influenza type A virus. Three-day-old mice mounted a greatly reduced primary NP(366-374)-specific CTL response when compared with 7-d-old and adult mice, whereas secondary CTL responses were normal. Analysis of NP(366-374)-specific CTL TCR repertoire revealed different Vbeta gene usage and greatly reduced public clonotypes in 3-d old neonates. This could underlie the impaired CTL response in these neonates. To directly test this, we examined whether controlling the TCR would restore neonatal CTL responses. We performed adoptive transfers of both nontransgenic and TCR-transgenic OVA(257-264)-specific (OT-I) CD8(+) T cells into influenza infected hosts, which revealed that naive neonatal and adult OT-I cells expand equally well in neonatal and adult hosts. In contrast, nontransgenic neonatal CD8(+) T cells when transferred into adults failed to expand. We further demonstrate that differences in TCR avidity may contribute to decreased expansion of the endogenous neonatal CTL. These studies highlight the rapid evolution of the neonatal TCR repertoire during the first week of life and show that impaired neonatal CTL immunity results from an immature TCR repertoire, rather than intrinsic signaling defects or a suppressive environment. PMID- 26873989 TI - Cutting Edge: Enhanced Clonal Burst Size Corrects an Otherwise Defective Memory Response by CD8+ Recent Thymic Emigrants. AB - The youngest peripheral T cells (recent thymic emigrants [RTEs]) are functionally distinct from naive T cells that have completed postthymic maturation. We assessed the RTE memory response and found that RTEs produced less granzyme B than their mature counterparts during infection but proliferated more and, therefore, generated equivalent target killing in vivo. Postinfection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating that the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. PMID- 26873990 TI - Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans. AB - Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL 1beta, IL-6, and TNF-alpha: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-gamma, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers. PMID- 26873991 TI - Cutting Edge: Mycobacterium tuberculosis Induces Aerobic Glycolysis in Human Alveolar Macrophages That Is Required for Control of Intracellular Bacillary Replication. AB - Recent advances in immunometabolism link metabolic changes in stimulated macrophages to production of IL-1beta, a crucial cytokine in the innate immune response to Mycobacterium tuberculosis. To investigate this pathway in the host response to M. tuberculosis, we performed metabolic and functional studies on human alveolar macrophages, human monocyte-derived macrophages, and murine bone marrow-derived macrophages following infection with the bacillus in vitro. M. tuberculosis infection induced a shift from oxidative phosphorylation to aerobic glycolysis in macrophages. Inhibition of this shift resulted in decreased levels of proinflammatory IL-1beta and decreased transcription of PTGS2, increased levels of anti-inflammatory IL-10, and increased intracellular bacillary survival. Blockade or absence of IL-1R negated the impact of aerobic glycolysis on intracellular bacillary survival, demonstrating that infection-induced glycolysis limits M. tuberculosis survival in macrophages through induction of IL 1beta. Drugs that manipulate host metabolism may be exploited as adjuvants for future therapeutic and vaccination strategies. PMID- 26873993 TI - Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion. AB - Streptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MPhi) receptor in the response to group B Streptococcus, both in bone marrow-derived MPhis and in mature tissue MPhis, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MPhis. Furthermore, a specific role for TLR13 with respect to MPhi function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow derived MPhis and microglia, but not in dermal MPhis. In summary, TLR13 is a critical and site-specific receptor in the single MPhi response to beta-hemolytic streptococci. PMID- 26873992 TI - Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans. AB - Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection in infants, causing significant morbidity and mortality. No vaccine or specific, effective treatment is currently available. A more complete understanding of the key components of effective host response to RSV and novel preventative and therapeutic interventions are urgently required. Cathelicidins are host defense peptides, expressed in the inflamed lung, with key microbicidal and modulatory roles in innate host defense against infection. In this article, we demonstrate that the human cathelicidin LL-37 mediates an antiviral effect on RSV by inducing direct damage to the viral envelope, disrupting viral particles and decreasing virus binding to, and infection of, human epithelial cells in vitro. In addition, exogenously applied LL-37 is protective against RSV-mediated disease in vivo, in a murine model of pulmonary RSV infection, demonstrating maximal efficacy when applied concomitantly with virus. Furthermore, endogenous murine cathelicidin, induced by infection, has a fundamental role in protection against disease in vivo postinfection with RSV. Finally, higher nasal levels of LL-37 are associated with protection in a healthy human adult RSV infection model. These data lead us to propose that cathelicidins are a key, nonredundant component of host defense against pulmonary infection with RSV, functioning as a first point of contact antiviral shield and having additional later-phase roles in minimizing the severity of disease outcome. Consequently, cathelicidins represent an inducible target for preventative strategies against RSV infection and may inform the design of novel therapeutic analogs for use in established infection. PMID- 26873994 TI - Metabolic Reprogramming Supports IFN-gamma Production by CD56bright NK Cells. AB - Human NK cells can be classified into phenotypically and functionally distinct subsets based on levels of CD56 receptor. CD56(dim) cells are generally considered more cytotoxic, whereas the CD56(bright) cells are potent producers of IFN-gamma. In this study, we define the metabolic changes that occur in peripheral blood NK cells in response to cytokine. Metabolic analysis showed that NK cells upregulate glycolysis and oxidative phosphorylation in response to either IL-2 or IL-12/15 cytokine combinations. Despite the fact that both these cytokine combinations robustly upregulated mammalian Target of Rapamycin Complex 1 in human NK cells, only the IL-2-induced metabolic changes were sensitive to mammalian Target of Rapamycin Complex 1 inhibition by rapamycin. Interestingly, we found that CD56(bright) cells were more metabolically active compared with CD56(dim) cells. They preferentially upregulated nutrient receptors and also differed substantially in terms of their glucose metabolism. CD56(bright) cells expressed high levels of the glucose uptake receptor, Glut1 (in the absence of any cytokine), and had higher rates of glucose uptake compared with CD56(dim) cells. Elevated levels of oxidative phosphorylation were required to support both cytotoxicity and IFN-gamma production in all NK cells. Finally, although elevated glycolysis was not required directly for NK cell degranulation, limiting the rate of glycolysis significantly impaired IFN-gamma production by the CD56(bright) subset of cells. Overall, we have defined CD56(bright) NK cells to be more metabolically active than CD56(dim) cells, which supports their production of large amounts of IFN-gamma during an immune response. PMID- 26873995 TI - Vaccine Targeting of Subdominant CD8+ T Cell Epitopes Increases the Breadth of the T Cell Response upon Viral Challenge, but May Impair Immediate Virus Control. AB - As a result of the difficulties in making efficient vaccines against genetically unstable viruses such as HIV, it has been suggested that future vaccines should preferentially target subdominant epitopes, the idea being that this should allow a greater breadth of the induced T cell response and, hence, a greater efficiency in controlling escape variants. However, to our knowledge the evidence supporting this concept is limited at best. To improve upon this, we used the murine lymphocytic choriomeningitis virus model and adenoviral vectors to compare a vaccine expressing unmodified Ag to a vaccine expressing the same Ag without its immunodominant epitope. We found that removal of the dominant epitope allowed the induction of CD8(+) T cell responses targeting at least two otherwise subdominant epitopes. Importantly, the overall magnitude of the induced T cell responses was similar, allowing us to directly compare the efficiency of these vaccines. Doing this, we observed that mice vaccinated with the vaccine expressing unmodified Ag more efficiently controlled an acute viral challenge. In the course of a more chronic viral infection, mice vaccinated using the vaccine targeting subdominant epitopes caught up with the conventionally vaccinated mice, and analysis of the breadth of the CD8(+) T cell response revealed that this was notably greater in the former mice. However, under the conditions of our studies, we never saw any functional advantage of this. This may represent a limitation of our model, but clearly our findings underscore the importance of carefully weighing the pros and cons of changes in epitope targeting before any implementation. PMID- 26873996 TI - From a Death Sentence to a Disrupted Life: Palestinian Women's Experiences and Coping With Breast Cancer. AB - This study explores women's experiences of breast cancer in the occupied Palestinian territory. We use an inductive qualitative design with a thematic analytical approach for conducting and analyzing 35 semi-structured interviews with breast cancer patients. The interviews focused on diagnosis, experiences and coping with breast cancer, social support and care needs, and the impact of illness on their families and social relationships. Three themes emerged: (a) the transition from initial shock to the daily struggles with disruptions caused by illness, (b) the role of social support in helping women cope with the burden of disease, and the importance of (c) faith and reliance on God (tawakkul). In the Palestinian context, women's narratives highlighted the disruptive nature of breast cancer. Our findings underline the importance of social support provided by extended family members. Finally, faith is an important overarching theme that influences how women make sense of and cope with breast cancer. PMID- 26873997 TI - Holistic Experiences and Strategies for Conducting Research With Couples. AB - In this article, we outline methodological considerations for conducting research interviews with couples. We draw from two qualitative men's health studies, both developed to explore social interactions between men and their partners of either sex in relation to their health practices. We utilized a combination of separate interviews and joint couple interviews. From these studies, we offer insight into our experiences of using both types of interview styles, addressing four key areas which span elements across the research project journey: (a) choosing a mode of interview, (b) ethical concerns in couple research, PMID- 26873998 TI - Living Well With a Long-Term Condition: Service Users' Perspectives of a Self Management Intervention. AB - The outcomes of self-management interventions are commonly assessed using quantitative measurement tools, and few studies ask people with long-term conditions to explain, in their own words, what aspects of the intervention they valued. In this Grounded Theory study, a Health Trainers service in the north of England was evaluated based on interviews with eight service-users. Open, focused, and theoretical coding led to the development of a preliminary model explaining participants' experiences and perceived impact of the service. The model reflects the findings that living well with a long-term condition encompassed social connectedness, changed identities, acceptance, and self-care. Health trainers performed four related roles that were perceived to contribute to these outcomes: conceptualizer, connector, coach, and champion. The evaluation contributes a grounded theoretical understanding of a personalized self management intervention that emphasizes the benefits of a holistic approach to enable cognitive, behavioral, emotional, and social adjustments. PMID- 26873999 TI - AG and UAG induce beta-casein expression via activation of ERK1/2 and AKT pathways. AB - The ghrelin peptides were found to circulate in two major forms: acylated ghrelin (AG) and unacylated ghrelin (UAG). Previous studies showed that AG regulates beta casein (CSN2) expression in mammary epithelial cells. However, little is known about the mechanisms by which AG regulates CSN2 gene and protein expression. Evidence suggests that UAG has biological activity through GHSR1a-independent mechanisms. Here, we investigated the possible GHSR1a-mediated effect of UAG on the expression of CSN2 in primary bovine mammary epithelial cells (pbMECs) isolated from lactating cow. We found that both AG and UAG increase the expression of CSN2 in a dose-dependent manner in pbMECs in comparison with the control group. Increased expression of CSN2 was blocked by [D-Lys3]-GHRP-6 (an antagonist of the GHSR1a) and NF449 (a Gs-alpha subunit inhibitor) in pbMECs. In addition, both AG and UAG activated AKT/protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways, whereas [D-Lys3]-GHRP-6 and NF449 inhibited the phosphorylation of AKT and ERK1/2 in pbMECs respectively. Blockade of ERK1/2 and AKT signaling pathways prevented the expression of CSN2 induced by AG or UAG. Finally, we found that both AG and UAG cause cell proliferation through identical signaling pathways. Taken together, these results demonstrate that both AG and UAG act on ERK1/2 and AKT signaling pathways to facilitate the expression of CSN2 in a GHSR1a-dependent manner. PMID- 26874000 TI - KLF6 cooperates with NUR77 and SF1 to activate the human INSL3 promoter in mouse MA-10 leydig cells. AB - Insulin-like 3 (INSL3), a Leydig cell-specific hormone, is essential for testis descent during foetal life and bone metabolism in adults. Despite its essential roles in male reproductive and bone health, very little is known regarding its transcriptional regulation in Leydig cells. To date, few transcription factors have been shown to activate INSL3 promoter activity: the nuclear receptors AR, NUR77, COUP-TFII and SF1. To identify additional regulators, we have isolated and performed a detailed analysis of a 1.1 kb human INSL3 promoter fragment. Through 5' progressive deletions and site-directed mutagenesis, we have mapped a 10 bp element responsible for about 80% of INSL3 promoter activity in Leydig cells. This element is identical to the CPE element of the placental-specific glycoprotein-5 (PSG5) promoter that is recognized by the developmental regulator Kruppel-like factor 6 (KLF6). Using PCR and western blotting, we found that KLF6 is expressed in several Leydig and Sertoli cell lines. Furthermore, immunohistochemistry on adult mouse testis revealed the presence of KLF6 in the nuclei of both Leydig and Sertoli cells. KLF6 binds to the 10 bp KLF element at 108 bp and activates the -1.1 kb human, but not the mouse, INSL3 promoter. KLF6 mediated activation of the human INSL3 promoter required an intact KLF element as well as Leydig/Sertoli-enriched factors because KLF6 did not stimulate the human INSL3 promoter activity in CV-1 fibroblast cells. Consistent with this, we found that KLF6 transcriptionally cooperates with NUR77 and SF1. Collectively, our results identify KLF6 as a regulator of human INSL3 transcription. PMID- 26874001 TI - eComment. The importance of choosing a proper predictor variable selection method in logistic regression analyses. PMID- 26874002 TI - eComment. Spontaneous conversion from atrial fibrillation to typical atrial flutter during the operation. PMID- 26874003 TI - eComment. What is the best perfusion strategy for minimally invasive mitral valve surgery in octogenarians? PMID- 26874004 TI - eComment. Creative solutions in order to treat sternal wound complications in cardiac surgery. PMID- 26874005 TI - eComment. Lung size mismatch and graft dysfunction immediately after reperfusion. PMID- 26874006 TI - eComment. An unusual cause of aortic mural thrombus in non-atherosclerotic vessel. PMID- 26874007 TI - eComment. Mural thrombus in normal appearing aorta: Unfinished saga in uncharted waters. PMID- 26874009 TI - Commentary: Post-GWAS era: What can we do beyond cancer genetic association studies? PMID- 26874010 TI - Cohort study for evaluation of dose omission without justification in a teaching general hospital in Bahia, Brazil. AB - OBJECTIVE: To evaluate the incidence of medication errors due to dose omissions and the reasons for non-administration of medications. DESIGN: A cohort study blinded to the nursing staff was conducted for 5 consecutive days to evaluate administration of prescribed medications to selected inpatients. SETTING: A major academic teaching hospital in Brazil. PARTICIPANTS: Dispensed doses to patients in medical and surgical wards. MAIN OUTCOME MEASURES: Doses returned to pharmacy were evaluated to identify the rate of dose omission without a justification for omission. RESULTS: Information was collected from 117 patients in 11 wards and 1119 doses of prescribed medications were monitored. Overall, 238/1119 (21%) dispensed doses were not administered to the patients. Among these 238 doses, 138 (58%) had no justification for not being administered. Failure in the administration of at least 1 dose occurred for 58/117 (49.6%) patients. Surgical wards had significantly more missed doses than that in medical wards (P = 0.048). The daily presence of a pharmacist in the wards was significantly correlated with lower frequency of omission errors (P = 0.019). Nervous system medications were missed more significantly than other medications (P < 0.001). No difference was noted in the omission doses in terms of route of administration. CONCLUSIONS: High incidence of omission errors occurs in our institution. Factors such as the deficit of nursing staff and clinical pharmacists and a weak medication dispensing system, probably contributed to incidence detected. Blinding nursing staff was essential to improve the sensibility of the method for detecting omission errors. PMID- 26874012 TI - Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin. AB - In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. PMID- 26874013 TI - Simultaneous visualization of two Citrus tristeza virus genotypes provides new insights into the structure of multi-component virus populations in a host. AB - Complex Citrus tristeza virus (CTV) populations composed of mixtures of different strains of the virus are commonly found in citrus trees in the field. At present, little is known about how these populations are formed, maintained, and how they are structured within a host. Here we used a novel in situ hybridization approach allowing simultaneous visualization of two different RNA targets with high sensitivity and specificity to examine the distribution of two isolates, T36 and T68-1, representing phylogenetically distinct strains of CTV, in a citrus host in single and mixed infections. Remarkably, in doubly inoculated plants the two virus variants appeared to be well mixed within the infected tissue and showed no spatial segregation. In addition, both CTV variants were often found occupying the same cells. Possible mechanisms involved in shaping CTV populations and the biological significance of the observed lack of structural separation of the individual components are discussed. PMID- 26874011 TI - Sf3b4-depleted Xenopus embryos: A model to study the pathogenesis of craniofacial defects in Nager syndrome. AB - Mandibulofacial dysostosis (MFD) is a human developmental disorder characterized by defects of the facial bones. It is the second most frequent craniofacial malformation after cleft lip and palate. Nager syndrome combines many features of MFD with a variety of limb defects. Mutations in SF3B4 (splicing factor 3b, subunit 4) gene, which encodes a component of the pre-mRNA spliceosomal complex, were recently identified as a cause of Nager syndrome, accounting for 60% of affected individuals. Nothing is known about the cellular pathogenesis underlying Nager type MFD. Here we describe the first animal model for Nager syndrome, generated by knocking down Sf3b4 function in Xenopus laevis embryos, using morpholino antisense oligonucleotides. Our results indicate that Sf3b4-depleted embryos show reduced expression of the neural crest genes sox10, snail2 and twist at the neural plate border, associated with a broadening of the neural plate. This phenotype can be rescued by injection of wild-type human SF3B4 mRNA but not by mRNAs carrying mutations that cause Nager syndrome. At the tailbud stage, morphant embryos had decreased sox10 and tfap2a expression in the pharyngeal arches, indicative of a reduced number of neural crest cells. Later in development, Sf3b4-depleted tadpoles exhibited hypoplasia of neural crest-derived craniofacial cartilages, phenocopying aspects of the craniofacial skeletal defects seen in Nager syndrome patients. With this animal model we are now poised to gain important insights into the etiology and pathogenesis of Nager type MFD, and to identify the molecular targets of Sf3b4. PMID- 26874014 TI - The aetiology of wobbly possum disease: Reproduction of the disease with purified nidovirus. AB - The objective of this study was to investigate a role of a recently discovered marsupial nidovirus in the development of a neurological disease, termed wobbly possum disease (WPD), in the Australian brushtail possum (Trichosurus vulpecula). Four possums received 1 mL of a standard inoculum that had been prepared from tissues of WPD-affected possums, 4 possums received 1.8 mL (1 * 10(6) TCID50) of a cell lysate from inoculated cultures, and 4 possums received 1 mL (* 10(7) TCID50) of a purified WPD isolate. All but one possum that received infectious inocula developed neurological disease and histopathological lesions characteristic for WPD. High levels of viral RNA were detected in livers from all possums that received infectious inocula, but not from control possums. Altogether, our data provide strong experimental evidence for the causative involvement of WPD virus in development of a neurological disease in infected animals. PMID- 26874015 TI - Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation. AB - Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced membrane rearrangements while EM using 'APEX2'-tagged viruses demonstrated S235D-mediated enrichment of NS5A in irregular membranous foci. Finally, using a customized siRNA screen of candidate NS5A kinases and subsequent analysis using a phospho-specific antibody, we show that phosphatidylinositol-4 kinase III alpha (PI4KIIIalpha) is important for Ser-235 phosphorylation. We conclude that Ser-235 phosphorylation of NS5A is essential for HCV RNA replication and normal replication complex formation and is regulated by PI4KIIIalpha. PMID- 26874016 TI - The microviridae: Diversity, assembly, and experimental evolution. AB - The Microviridae, comprised of ssDNA, icosahedral bacteriophages, are a model system for studying morphogenesis and the evolution of assembly. Historically limited to the phiX174-like viruses, recent results demonstrate that this richly diverse family is broadly divided into two groups. The defining feature appears to be whether one or two scaffolding proteins are required for assembly. The single-scaffolding systems contain an internal scaffolding protein, similar to many dsDNA viruses, and have a more complex coat protein fold. The two scaffolding protein systems (phiX174-like) encode an internal and external species, as well as an additional structural protein: a spike on the icosahedral vertices. Here, we discuss recent in silico and in vivo evolutionary analyses conducted with chimeric viruses and/or chimeric proteins. The results suggest 1) how double scaffolding systems can evolve into single and triple scaffolding systems; and 2) how assembly is the critical factor governing adaptation and the maintenance of species boundaries. PMID- 26874017 TI - Genomic analyses reveal that partial sequence of an earlier pseudorabies virus in China is originated from a Bartha-vaccine-like strain. AB - Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, has gained increased attention in China in recent years as a result of the outbreak of emergent pseudorabies. Several genomic and partial sequences are available for Chinese emergent and European-American strains of PRV, but limited sequence data exist for the earlier Chinese strains. In this study, we determined the complete genomic sequence of one earlier Chinese strain SC and one emergent strain HLJ8. Compared with other known sequences, we demonstrated that PRV strains from distinct geographical regions displayed divergent evolution. Additionally, we report for the first time, a recombination event between PRV strains, and show that strain SC is a recombinant of an endemic Chinese strain and a Bartha-vaccine like strain. These results contribute to our understanding of PRV evolution. PMID- 26874018 TI - Immediate Versus Delayed Treatment of Mandibular Fractures: A Stratified Analysis of Complications. AB - PURPOSE: To analyze the rate of complication outcomes of mandibular fracture repairs across different injury-to-repair time spans. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients with repaired mandibular fractures. The independent variable was the time span from injury to surgical repair. The primary outcome variable was the rate of complications measured postoperatively during the follow-up appointments. Other variables were grouped for performance of a stratified analysis: favorability of the fracture, patient compliance, substance abuse, and fracture location. Descriptive and bivariate statistics were computed. RESULTS: The final sample was composed of 505 patients, and the time span from injury to repair ranged from 0 to 90 days. The total number of patients from the sample with reported complications was 124. There was no statistical significance correlating the time spans and complication rates (P = .796). The variables for the stratified analysis also showed no significant correlations except for fracture location. Body fractures resulted in the highest rate of complications (33%; P = .041). Of the noncompliant patients (n = 144), 28.5% presented with complications (P = .352). No significance was seen in unfavorable fractures (n = 283), with a rate of complications of 28.6%. No significance could be correlated with substance abuse (n = 107, 29.9% with complications; P = .262). CONCLUSIONS: The results of this study suggest that although time from injury to repair does not affect the rate of complications, the global standard of care for the management of non-emergent mandibular fractures should consider the cost-effectiveness of delaying treatment while exercising a reasonable length of delay for the comfort of the patient. PMID- 26874019 TI - Sensitive analysis of alpha-synuclein by nonlinear laser wave mixing coupled with capillary electrophoresis. AB - Multi-photon nonlinear laser wave-mixing spectroscopy is a novel absorption-based technique that offers excellent detection sensitivity for biomedical applications, including early diagnosis and investigation of neurodegenerative diseases. alpha-Synuclein is linked to Parkinson's disease (PD), and characterization of its oligomers and quantification of the protein may contribute to understanding PD. The laser wave-mixing signal has a quadratic dependence on analyte concentration, and hence the technique is effective in monitoring small changes in concentration within biofluids. A wide variety of labels can be employed for laser wave-mixing detection due to its ability to detect both chromophores and fluorophores. In this investigation, two fluorophores and a chromophore are studied and used as labels for the detection of alpha-synuclein. Wave-mixing detection limits of PD-related protein conjugated with fluorescein isothiocyanate, QSY 35 acetic acid, succinimidyl ester, and Chromeo P503 were determined to be 1.4 * 10(-13) M, 1.4 * 10(-10) M, and 1.9 * 10(-13) M, respectively. Based on the laser probe volume used, the corresponding mass detection limits were determined to be 1.1 * 10(-23) mol, 1.1 * 10(-20) mol, and 1.5 * 10(-23) mol. This study also presents molecular-based separation and quantification of alpha-synuclein by laser wave mixing coupled with capillary electrophoresis. PMID- 26874020 TI - Protocol for miRNA isolation from biofluids. AB - MicroRNAs (miRNAs) have been identified as promising biomarkers in cancer and other diseases. Packaging of miRNAs into vesicles and complexes with proteins ensures their stability in biological fluids but also complicates their isolation. Conventional protocols used to isolate cell-free RNA are generally successful in overcoming these difficulties; however, they are costly, labor intensive, or heavily reliant on the use of hazardous chemicals. Here we describe a protocol that is suitable for isolating miRNAs from biofluids, including blood plasma and urine. The protocol is based on precipitation of proteins, denaturation of miRNA-containing complexes with octanoic acid and guanidine isothiocyanate, and subsequent purification of miRNA on spin columns. The efficacy of miRNA extraction by phenol-chloroform extraction, miRCURY RNA isolation kit--biofluids (Exiqon), and the proposed protocol was compared by quantitative reverse-transcription PCR of miR-16 and miR-126. The proposed protocol was slightly more effective for isolating miRNA from plasma and significantly superior to the other two methods for miRNA isolation from urine. Spectrophotometry and SDS-PAGE data suggest that the disparity in performance between miRCURY Biofluids and the proposed protocol can be attributed to differences in precipitation mechanisms, as confirmed by the retention of different proteins in the supernatant. PMID- 26874022 TI - Letter to Editor, International Journal of Pharmaceutics. PMID- 26874023 TI - Response to letter to editor. PMID- 26874021 TI - Development of a RapidFire mass spectrometry assay and a fluorescence assay for the discovery of kynurenine aminotransferase II inhibitors to treat central nervous system disorders. AB - Kynurenine aminotransferases convert kynurenine to kynurenic acid and play an important role in the tryptophan degradation pathway. Kynurenic acid levels in brain have been hypothesized to be linked to a number of central nervous system (CNS) disorders. Kynurenine aminotransferase II (KATII) has proven to be a key modulator of kynurenic acid levels in brain and, thus, is an attractive target to treat CNS diseases. A sensitive, high-throughput, label-free RapidFire mass spectrometry assay has been developed for human KATII. Unlike other assays, this method is directly applicable to KATII enzymes from different animal species, which allows us to select proper animal model(s) to evaluate human KATII inhibitors. We also established a coupled fluorescence assay for human KATII. The short assay time and kinetic capability of the fluorescence assay provide a useful tool for orthogonal inhibitor validation and mechanistic studies. PMID- 26874024 TI - Effects of occlusal disharmony on the hippocampal dentate gyrus in aged senescence-accelerated mouse prone 8 (SAMP8). AB - BACKGROUND AND OBJECTIVE: Malocclusion induced by raising the bite causes chronic stress. Chronic stress leads to increased plasma corticosterone levels and impaired hippocampal function due to impaired neurogenesis or increased apoptosis in the hippocampus. The present study aimed to clarify the mechanisms underlying the impaired hippocampal function induced by the bite-raised condition in aged senescence-accelerated mouse prone 8 (SAMP8). DESIGN: Nine-month-old aged SAMP8 mice were randomly divided into control and bite-raised groups. The vertical dimension of the bite was raised by applying resin to the molars. We evaluated newborn cell proliferation, survival, differentiation, and apoptosis in the hippocampal dentate gyrus (DG). Hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. RESULTS: The bite-raised mice exhibited a significant decrease in proliferation, survival, and differentiation of newborn cells into neurons in the hippocampal DG compared with controls. The number of apoptotic cells in the hippocampal DG was increased at 7 and 14 days after the bite-raising procedure. Expression of BDNF protein and mRNA in the hippocampus was also decreased in the bite-raised mice. CONCLUSION: Bite-raised aged SAMP8 mice exhibited decreased neurogenesis, increased apoptosis in the hippocampal DG, and decreased hippocampal BDNF expression, in association with hippocampus dependent learning and memory deficits. PMID- 26874025 TI - "Angiotensin II memory" contributes to the development of hypertension and vascular injury via activation of NADPH oxidase. AB - AIMS: Activation of the rennin-angiotensin system plays a critical role in the development of hypertension and its complication. Our previous study has demonstrated that a cellular "memory" is involved in angiotensin II (Ang II) induced cardiac hypertrophy. The aim of this study is to investigate the effect of reversal of high Ang II to normal condition on hypertension and vascular damage. MAIN METHODS: Wild-type male mice were randomly divided into five groups. The vascular function, inflammation, oxidative stress and angiogenesis were examined by aortic ring relaxation studies, histological analysis, real-time PCR and Western blot analysis. KEY FINDINGS: We found that continuous high Ang II infusion for 3weeks (Ang II 3w) significantly elevated blood pressure, increased aortic wall thickness, collagen deposition, inflammation, oxidative stress, vascular function and activation of p38 MAPK, JNK1/2, STAT3 and NF-kappaB pathways in mouse aorta compared with saline group. High Ang II exposure for 2weeks followed by saline for 1week (Ang II 2+1w) failed to reverse these alterations. This phenomenon was named "metabolic memory" (or persistent effect). However, addition of NADPH oxidase inhibitor apocynin during saline infusion (Ang II 2+1w+Apo) markedly ameliorated such deleterious effects. SIGNIFICANCE: These results showed that we report the first that persistent effect or "metabolic memory" of angiotensin II through NADPH oxidase-mediated oxidative stress plays important roles in hypertension and vascular injury. PMID- 26874026 TI - Suckling-induced Fos activation and melanin-concentrating hormone immunoreactivity during late lactation. AB - AIMS: Melanin-concentrating hormone (MCH) is implicated in the control of food intake, body weight regulation and energy homeostasis. Lactation is an important physiological model to study the hypothalamic integration of peripheral sensory signals, such as suckling stimuli and those related to energy balance. MCH can be detected in the medial preoptic area (MPOA), especially around the 19th day of lactation, when this hormone is described as displaying a peak synthesis followed by a decrease after weaning. The physiological significance of this phenomenon is unclear. Therefore, we aimed to investigate hypothalamic changes associated to sensory stimulation by the litter, in special its influence over MCH synthesis. MAIN METHODS: Female Wistar rats (n=56) were euthanized everyday from lactation days 15-21, with or without suckling stimulus (WS and NS groups, respectively). MCH and Fos immunoreactivity were evaluated in the MPOA and lateral and incerto hypothalamic areas (LHA and IHy). KEY FINDINGS: Suckling stimulus induced Fos synthesis in all regions studied. An increase on the number of suckling-induced Fos-ir neurons could be detected in the LHA after the 18th day. Conversely, the amount of MCH decreased in the MPOA from days 15-21, independent of suckling stimulation. No colocalization between MCH and Fos could be detected in any region analyzed. SIGNIFICANCE: Suckling stimulus is capable of stimulating hypothalamic regions not linked to maternal behavior, possibly to mediate energy balance aspects of lactation. Although dams are hyperphagic before weaning, this behavioral change does not appear to be mediated by MCH. PMID- 26874027 TI - Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells. AB - AIMS: Reactive oxygen species have been recognized to impair cell function through suppressing Akt the well-known pro-survival molecule. Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress. MAIN METHODS: In the current study using H2O2 induced injury in PC12 cells; we first examined metformin impact on cell death by MTT assay and visual assessment. Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post transcriptional changes. The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment. KEY FINDINGS: According to cells morphology and MTT data metformin led to significant protection against H2O2 induced injury in 0.1 and 0.5mM concentrations. Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels. These changes paralleled with a profound decline in the corresponding transcripts as determined by real time PCR. SIGNIFICANCE: Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin alleviating effect. The present work while highlighting metformin anti-oxidant characteristics, concludes that Akt/mTOR signaling might be central to the drug's alleviating effects. PMID- 26874028 TI - Structural changes in gastric glial cells and delayed gastric emptying as responses to early life stress and acute adulthood stress in rats. AB - AIM: Enteric glial cells (EGCs) modulate colonic motility in a maternal separation model. We aimed to investigate structural changes in gastric EGC and gastric emptying as responses to maternal separation and acute adulthood stress in rats to elucidate the pathophysiological roles of gastric EGC. MAIN METHODS: As a chronic stress, we subjected male Wistar rats to 3h of maternal separation during postnatal days 2-14. As an acute adulthood stress (7weeks of age), we used the 8-h water-immersion method. We morphologically evaluated gastric EGCs using whole-mount longitudinal muscle-myenteric plexus preparations. We analyzed gastric emptying by the phenol red method. KEY FINDING: The area of EGC processes that apparently overlapped with neurons increased according to stress intensity (acute stress, 10.4%; maternal separation, 10.2%; maternal separation plus acute stress, 26.6%; control, 5.0%). Ratios of morphologically changed leaf-like processes to the total processes were 8.1%, acute stress; 10.3%, maternal separation; 4.0%, control. Ratio dramatically increased in the combined stress group (20.5%, p=0.026 vs. control). The mean bulging head area of leaf-like processes in the combined stress group was greater by 6.4MUm(2) (control, 2.4MUm(2); p=0.042). Gastric emptying in the maternal separation group was gradually delayed (104.1% at 7weeks, 66.7% at 17weeks, and 48.5% at 48weeks; p<0.05, respectively). Gastric emptying in the combined stress group tended to be delayed at 17weeks (45.7% vs. 81% in controls, p=0.066). SIGNIFICANCE: Gastric EGCs exhibited structural changes according to stress intensity, which may be associated with stress-induced dysfunction of the stomach. PMID- 26874029 TI - NOD2 contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and inflammation. AB - AIMS: Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), an intracellular pattern recognition receptor, which plays an important role in the innate immunity and inflammation. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. In this study, we sought to determine the role of NOD2 on cardiac I/R injury. MAIN METHODS: Mice were induced 30min ischemia followed by 24h of reperfusion. Histological examinations were performed on heart sections with Evans blue and triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, immunohistochemistry and immunofluorescence staining. The messenger RNA (mRNA) expression and protein levels were detected by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. KEY FINDINGS: I/R injury markedly upregulated NOD2 expression in heart tissue. Treatment of WT mice with NOD2 ligand (MDP) significantly increased infarct size, the number of apoptotic cells and inflammatory cells, as compared with wild-type mice after I/R injury. Furthermore, MDP enhanced I/R-induced cardiomyocyte apoptosis and inflammation in vitro, and these effects were attenuated by NOD2-siRNA. The mechanism of NOD2 on cardiac I/R injury is partly associated with JNK, p38MAPK and NF-kappaB signaling pathways. SIGNIFICANCE: NOD2 aggravates myocardial I/R injury by inducing cardiomyocyte apoptosis and inflammation through JNK, p38MAPK and NF-kappaB signaling pathways. This study provides insight into better understanding the molecular mechanism of NOD2, which may be served as a potential target for the treatment of myocardial I/R injury. PMID- 26874030 TI - Antigenic role of the adaptive immune response to d-ribose glycated LDL in diabetes, atherosclerosis and diabetes atherosclerotic patients. AB - AIMS: Glycation of proteins leads to the formation of advanced glycation end products (AGEs, which have significant role in the pathophysiology of diabetes complications. d-ribose appears to be the most reactive among the naturally occurring sugars and contribute significantly to the generation of AGEs. Glycation also results in the generation of free radicals causing structural modification which leads to the generation of neoantigenic epitopes. The aim of the present study was to investigate whether LDL modification results in auto antibodies formation against its glycated conformer in diabetes and atherosclerosis patients. METHODS: The binding characteristics of circulating auto-antibodies in patients against native and modified LDL were assessed. T2D (n=105), ATH (n=106) and T2D-ATH patients (n=72) were examined by direct binding ELISA as well as inhibition ELISA, compared with healthy age-matched controls (n=50). Furthermore, ketoamine moieties, HMF and carbonyl content were also estimated in these patient's and healthy subjects. KEY FINDINGS: High degree of specific binding was observed by 41.91% of T2D, 54.72% of ATH and 70.83% T2D-ATH patient's sera towards d-ribose glycated LDL, in comparison to its native analog (P<0.05). Normal human sera showed negligible binding with either antigen. Competitive inhibition ELISA reiterates the direct binding results. The higher concentration of HMF, ketoamine and carbonyl content was observed in patient's sera than healthy subjects. SIGNIFICANCE: LDL glycation results in structural perturbation causing generation of neoantigenic epitopes that are better antigens for antibodies in T2D, ATH and T2D-ATH patients where T2D-ATH subjects showed higher prevalence in auto-antibodies against ribosylated LDL. PMID- 26874031 TI - Endothelin ETA receptors predominate in chronic thromboembolic pulmonary hypertension. AB - AIMS: Endothelin-1 levels are raised in chronic thromboembolic pulmonary hypertension. Our aim in this study was to identify the presence of endothelin receptors in patients with CTEPH by analysing tissue removed at pulmonary endarterectomy. MAIN METHODS: Pulmonary endarterectomy tissue cross-sections were analysed using autoradiography with [(125)I]-ET-1 using ligands selective for ETA or ETB to determine sub-type distribution. The precise cellular localisation of ETA and ETB receptors was determined using selective antisera to both sub-types and compared with haematoxylin and eosin, Elastic Van Gieson and smooth muscle actin labelled sections. KEY FINDINGS: Two patterns of ET-1 binding were found. In sections with frequent recanalised channels, ET-1 bound to the smooth muscle cells surrounding the channels. In sections where there was less organised thrombus with no obvious re-canalisation, minimal ET-1 binding was observed. Some contractile type smooth muscle cells not associated with recanalised channels and diffusely spread throughout the PEA material were associated with ET receptor antibody binding on immunohistochemistry. There was a greater expression of the ETA receptor type in the specimens. SIGNIFICANCE: The presence of ET-1 receptors in the chronic thrombus in proximal CTEPH suggests ET-1 could act not only on the distal vasculopathy in the unobstructed vessels but may also stimulate smooth muscle cell proliferation within chronic clot. The abundance of ET receptors within the tissue provides evidence that the ET pathway is involved in the pathology of chronic thrombus reorganisation leading to CTEPH providing a rationale for the repurposing of ET receptor antagonists in the treatment of this condition. PMID- 26874032 TI - Bioactivity assessment of PLLA/PCL/HAP electrospun nanofibrous scaffolds for bone tissue engineering. AB - AIMS: The purpose of this paper was to fabricate PLLA/PCL nanofibrous scaffolds containing HAP to mimic the native bone extracellular matrix for potential applications as bone tissue engineering scaffolds materials and ultimately to help the repairing of bone defects. MATERIALS AND METHODS: PLLA (MW 200kDa), PCL (MW 80kDa), HAP, dichloromethane, N,N-dimethylformamide; alpha-MEM, FBS, trypsin EDTA, penicillin G, streptomycin, beta-sodium glycerophosphate, l-ascorbic acid, dexamethasone; CCK-8, Alkaline Phosphatase Assay Kit, Mouse Osteocalcin ELISA Kit, MC3T3-E1 cells. PLLA, PCL and HAP were dissolved in the solution of DCM and DMF to fabricate nanofibrous scaffolds through electrospinning. The morphology of the scaffolds was investigated with SEM, while the diameter of the fibers, pore size and water uptake of the scaffolds were tested, respectively. TGA was carried out to verify the percentage of HAP in the composite scaffolds fabricated with different HAP concentrations. Cell count kit-8 assay, alkaline phosphatase (ALP) assay, and osteocalcin assay were applied to observe the MC3T3-E1 cells proliferation, differentiation on the composite scaffolds. KEY FINDINGS: MC3T3-E1 cells were found to grow actively on the composite scaffolds based on the results of CCK-8 assay. The level of MC3T3-E1 differentiation was evaluated through the ALP activity and osteocalcin concentration, which showed higher value with HAP containing (PLLA/PCL/HAP) than that ones without (PLLA/PCL). SIGNIFICANCE: The results demonstrated that the biocomposite PLLA/PCL/HAP nanofibrous scaffold should be a promising candidate for proliferation, differentiation and mineralization of osteoblasts, and potentially can be used for bone tissue regeneration. PMID- 26874033 TI - Low dose aspirin like analgesic and anti-inflammatory activities of mono hydroxybenzoic acids in stressed rodents. AB - AIMS: To compare analgesic and anti-inflammatory activities of aspirin and mono hydroxybenzoic acids after their daily oral doses. MAIN METHODS: Efficacies of repeated daily stress response suppressing low oral doses (20mg/kg) of aspirin and 2-, 3-, and 4-hydroxybenzoic acids in mice hot plate test for centrally acting analgesics, and in acetic acid induced writing test were compared. Effects of their same daily doses and treatment regimen in cotton pellet granuloma and carrageenan edema test for anti-inflammatory drugs in stressed rats were compared in a second experiment. Effects of treatments on body weights, basal rectal temperatures, organ weights and plasma glucose, insulin and cortisol levels in stressed animals were compared also. KEY FINDINGS: Although stress response suppressing effects of aspirin and all the three hydroxybenzoic acids in both mice and rats were almost equal, effectiveness of 3- and 4-hydroxybenzoic acids as analgesic and anti-inflammatory agents were lower than those of aspirin or salicylic acid. SIGNIFICANCE: Observations made after single oral doses of aspirin or of mono-hydroxybenzoic acids are not very reliable predictors of their pharmacologically interesting bioactivity profiles and efficacies. Prostaglandin synthesis inhibition is not involved in low dose anti-inflammatory activities of 3- and 4-hydroxybenzoic acids. After their repeated daily low oral doses they are almost as potent stress response desensitizers as aspirin or salicylic acid. PMID- 26874034 TI - Neuroprotective effects of phytosterols and flavonoids from Cirsium setidens and Aster scaber in human brain neuroblastoma SK-N-SH cells. AB - AIMS: We investigated the neuroprotective effects and action mechanism of three major compounds [daucosterol (Dau), pectolinarin (Pec), and astragalin (Ast)] isolated from edible plants against H2O2-induced cell death of human brain neuroblastoma SK-N-SH cells. MAIN METHODS: Cytotoxicity was determined by MTT and lactate dehydrogenase (LDH) assays. Apoptotic cell death was monitored by annexin V-FITC/PI double staining and by TUNEL assay. The formation of reactive oxygen species (ROS), expression of antioxidant enzymes and phosphorylation of mitogen activated protein kinase (MAPK) were determined by 2,7-dichlorofluorescein diacetate (DCF-DA) assay, RT-PCR, and western blotting, respectively. KEY FINDINGS: The ethyl acetate fractions from Cirsium setidens (CSEA) and Aster scaber (ASEA) showed neuroprotective effects in SK-N-SH cells. The phytochemicals were isolated from CSEA and ASEA and identified by spectral analyses, as beta sitosterol, Dau, Pec, Ast, or isoquercitrin. Pretreatment with Dau, Pec, or Ast showed protective effects against H2O2-induced cell death and inhibited ROS generation by oxidative stress. HO-1 mRNA and protein levels were increased by the presence of H2O2 and were further elevated by pretreatment with Dau and Ast. Dau pretreatment resulted in further increases of H2O2-induced enhancement in levels of CAT and SOD2. Pretreatment with Dau, Pec, and Ast inhibited phosphorylation of MAPK, such as extracellular protein regulated protein kinase, p38, and c-Jun N-terminal kinase by H2O2. SIGNIFICANCE: Dau exerts its neuroprotective effects by down regulation of MAPK pathways and upregulation of the HO-1, CAT and SOD2 antioxidant genes and is associated with reduced oxidative stress in SK-N-SH cells. PMID- 26874035 TI - Dictyoceratidan poisons: Defined mark on microtubule-tubulin dynamics. AB - Tubulin/microtubule assembly and disassembly is characterized as one of the chief processes during cell growth and division. Hence drugs those perturb these process are considered to be effective in killing fast multiplying cancer cells. There is a collection of natural compounds which disturb microtubule/tubulin dis/assemblage and there have been a lot of efforts concerted in the marine realm too, to surveying such killer molecules. Close to half the natural compounds shooting out from marine invertebrates are generally with no traceable definite mechanisms of action though may be tough anti-cancerous hits at nanogram levels, hence fatefully those discoveries conclude therein without a capacity of translation from laboratory to pharmacy. Astoundingly at least 50% of natural compounds which have definite mechanisms of action causing disorders in tubulin/microtubule kinetics have an isolation history from sponges belonging to the Phylum: Porifera. Poriferans have always been a wonder worker to treat cancers with a choice of, yet precise targets on cancerous tissues. There is a specific order: Dictyoceratida within this Phylum which has contributed to yielding at least 50% of effective compounds possessing this unique mechanism of action mentioned above. However, not much notice is driven to Dictyoceratidans alongside the order: Demospongiae thus dictating the need to know its select microtubule/tubulin irritants since the unearthing of avarol in the year 1974 till date. Hence this review selectively pinpoints all the compounds, noteworthy derivatives and analogs stemming from order: Dictyoceratida focusing on the past, present and future. PMID- 26874036 TI - Types and density of calbindin D28k-immunoreactive ganglion cells in mouse retina. AB - Single-cell injection after immunocytochemistry is a reliable technique for classifying neurons by their morphological structure and their expression of a particular protein. The aim of the present study was to classify the morphological types of calbindin D28k-immunoreactive retinal ganglion cells in the mouse using single-cell injection after immunocytochemistry, to estimate the density of calbindin D28k-immunoreactive retinal ganglion cells in the mouse retina. Calbindin D28k is an important calcium-binding protein that is widely expressed in the central nervous system. Calbindin D28k-immunoreactive retinal ganglion cells were identified by immunocytochemistry and then iontophoretically injected with the lipophilic dye, DiI. Subsequently, the injected cells were imaged by confocal microscopy to classify calbindin D28k-immunoreactive retinal ganglion cells based on their dendritic ramification depth within the inner plexiform layer, field size, and morphology. The cells were heterogeneous in morphology: monostratified or bistratified, with small to large dendritic field size and sparse to dense dendritic arbors. At least 10 different morphological types (CB1-CB10) of calbindin D28k-immunoreactive retinal ganglion cells were found in the mouse retina. The density of each cell type was quite variable (1.98 23.76%). The density of calbindin D28k-immunoreactive cells in the ganglion cell layer of the mouse retina was 562 cells/mm(2), 8.18% of calbindin D28k immunoreactive cells were axon-less displaced amacrine cells, 91.82% were retinal ganglion cells, and approximately 18.17% of mouse retinal ganglion cells expressed calbindin D28k. The selective expression of calbindin D28k in cells with different morphologies may provide important data for further physiological studies of the mouse retina. PMID- 26874037 TI - Semi-empirical chemical model for indirect advanced oxidation of Acid Orange 7 using an unmodified carbon fabric cathode for H2O2 production in an electrochemical reactor. AB - A commercial Unidirectional Carbon Fabric piece was used to design an electrode for the cathodic O2 reduction reaction in a divided (by a Nafion((r)) 117 membrane) parallel plate reactor. The anode was a commercial stainless steel mesh. Under this approach it is feasible to produce H2O2 at low energy (2.08 kWh kg(-1) H2O2) in low ionic acidic medium. In the catholyte side the H2O2 can be activated with Fe(2+) to develop the Fenton reagent. It was found that Acid Orange 7 (AO7) indirect oxidation (in the concentration range of 0.12-0.24 mM) by Fenton chemistry follows a first order kinetic equation. The energy required for 0.24 mM AO7 degradation is 1.04 kWhm(-3). From each experimental AO7 oxidation the main parameters (a, mM and k, min(-1)) of the first order kinetic equation are obtained. These parameters can be correlated with AO7 concentration in the concentration range studied. Based on this method a semi-empirical chemical model was developed to predict the AO7 abatement, by means of Fenton chemistry. Good AO7 oxidation predictions can be made in the concentration range studied. A detailed discussion of the energy required for oxidizing AO7 and the accuracy of the chemical model to predict its oxidation is included in this paper. PMID- 26874038 TI - Values of osteoprotegerin in aortic valve tissue in patients with significant aortic stenosis depend on the existence of concomitant coronary artery disease. AB - INTRODUCTION: Calcific aortic valve stenosis (CAVS) is a serious clinical problem. The strongest predictor of CAVS progression is the amount of calcium in the aortic valve. The pathogenesis of CAVS is largely consistent with the pathogenesis of atherosclerosis; however, about 50% of patients with CAVS do not exhibit significant atherosclerosis. Cardiovascular calcification is currently considered an actively regulated process, in which the important role is attributed to the RANKL/RANK/OPG (receptor activator of nuclear factor kappaB ligand/RANK/osteoprotegerin) axis. We measured OPG levels in the tissue of calcified, stenotic aortic valves in relation to the presence or absence of coronary artery disease (CAD). MATERIALS AND METHODS: Aortic valve samples were collected from 105 patients with calcified, mainly severe aortic stenosis, who were divided into two groups according to the presence of CAD. In Group A (n=44), there were normal coronary artery findings, while in Group B (n=61), there was angiographically demonstrated >50% stenosis of at least one coronary artery. The control Group C (n=21) consisted of patients without aortic stenosis and with normal angiographic findings on coronary arteries. RESULTS: The highest tissue concentrations of OPG [median (pmol/L), 25th-75th percentile] were found in Group A [6.95, 3.96-18.37], which was significantly different compared to the other two groups (P=.026 and .001, respectively). The levels of OPG in Group B [4.15, 2.47 9.16] and in Group C [2.25, 1.01-5.08] did not differ significantly (P=.078); however, the lowest concentrations of OPG were found in Group C. Neither age nor gender in our study had effect on tissue levels of OPG (P=.994 for gender; P=.848 for age). CONCLUSION: Calcified and narrowed aortic valves, compared to the normal valves, were accompanied by a change in tissue concentrations of OPG, which is, in addition, dependent on the presence or absence of CAD. The highest tissue concentrations of OPG in our work were found in patients with significant aortic stenosis without concomitant CAD. PMID- 26874039 TI - Comparison of calcification potential of valvular interstitial cells isolated from individual aortic valve cusps. AB - BACKGROUND: Calcific aortic valve disease (CAVD) is one of the most prevalent disorders among the elderly in developed countries. CAVD develops via cell mediated processes, and clinical data show that CAVD initiates mostly in the noncoronary cusp of the aortic valve. Valvular interstitial cells (VICs) populate the inside of heart valves and are a heterogeneous cell population. The goal of this study is to elucidate the difference in calcification potential among VICs isolated from the left, right, and noncoronary cusps of porcine aortic valves. METHODS AND RESULTS: VICs were isolated from each of the aortic valve cusps and cultured in calcifying medium for 14days to induce calcification. The samples were assessed for calcium deposits, nodule formation, and calcific markers using alizarin red and Von Kossa staining, alkaline phosphatase (ALP) staining, ALP enzyme activity assay, and Western blot. Extracellular matrix production and degradation were measured using collagen and glycosaminoglycan (GAG) assay and gelatin zymography. We observed that VICs isolated from the noncoronary cusp expressed greatest amount of the above calcific markers as compared to the coronary cusps. Also, collagen and GAG content was the greatest in noncoronary VICs. However, our zymography results showed significant difference only for active matrix metalloproteinase-2 expression between right and noncoronary VICs. CONCLUSION: Our results suggest that VICs among the three cusps within aortic valve might be inherently different, where a subpopulation of VICs might be predisposed to calcification. PMID- 26874040 TI - A case of familial calcific aortic and mitral stenosis in association with hereditary sclerosing poikiloderma. AB - Hereditary sclerosing poikiloderma is a rare, familial disease with the primary clinical features being dermatologic. Widespread poikiloderma, as well as linear hyperkeratotic and sclerotic bands, tends to be the most common sign of this disease. It has been suggested that cardiac involvement may represent an important element of this disorder; however, this has not been well studied. We confirm here a case of hereditary sclerosing poikiloderma in a patient and his family with significant cardiac involvement characterized by heavily calcified stenotic aortic and mitral valves on echocardiography. Due to the patient's symptomatic severe valvular disease, he underwent simultaneous aortic and mitral valve replacement. Histopathologic analysis of the valves confirmed severe calcification of the aortic and mitral valve leaflets, suggesting a potential common mechanism between the cardiac and skin pathology of this disease. Multiple other family members had presented with similar cardiac and skin manifestations. Further research is needed to better understand the cardiac pathophysiology of this disease. PMID- 26874041 TI - Postoperative plasma 8-iso-prostaglandin F2alpha levels are associated with delirium and cognitive dysfunction in elderly patients after hip fracture surgery. AB - BACKGROUND: Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2alpha (8 iso-PGF2alpha), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso PGF2alpha levels to predict POD and POCD in elderly patients undergoing hip fracture surgery. METHODS: Postoperative plasma 8-iso-PGF2alpha levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2alpha levels and the risk of POD and POCD using a multivariate analysis. RESULTS: Plasma 8-iso-PGF2alpha levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso PGF2alpha were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2alpha significantly enhanced the areas under curve of age for prediction of POD and POCD. CONCLUSIONS: Postoperative plasma 8 iso-PGF2alpha levels may have the potential to predict POD and POCD in elder patients undergoing hip fracture surgery. PMID- 26874042 TI - New mutations in DYNC2H1 and WDR60 genes revealed by whole-exome sequencing in two unrelated Sardinian families with Jeune asphyxiating thoracic dystrophy. AB - Jeune asphyxiating thoracic dystrophy (JATD; Jeune syndrome, MIM 208500) is a rare autosomal recessive chondrodysplasia, phenotypically overlapping with short rib polydactyly syndromes (SRPS). JATD typical hallmarks include skeletal abnormalities such as narrow chest, shortened ribs, limbs shortened bones, extra fingers and toes (polydactyly), as well as extraskeletal manifestations (renal, liver and retinal disease). To date, disease-causing mutations have been found in several genes, highlighting a marked genetic heterogeneity that prevents a molecular diagnosis of the disease in most families. Here, we report the results of whole-exome sequencing (WES) carried out in four JATD cases, belonging to three unrelated families of Sardinian origin. The exome analysis allowed to identify mutations not previously reported in the DYNC2H1 (MIM 603297) and WDR60 (MIM 615462) genes, both codifying for ciliary intraflagellar transport components whose mutations are known to cause Jeune syndrome. PMID- 26874043 TI - Diagnosis of acute myocardial infarction in hemodialysis patients may be feasible by comparing variation of cardiac troponins during acute presentation to baseline variation. AB - Acute myocardial infarction (AMI) is defined as a dynamic change in cardiac troponin (cTn) with at least one cTn value exceeding the 99 th percentile of a reference population in combination with typical clinical symptoms. In hemodialysis (HD) patients, a broad range of cTn concentrations is found, partially due to patient-specific comorbidities. Therefore, the 99 th percentile cannot be used in HD patients and decision algorithms to diagnose AMI should be based on temporal variations of troponin. In this study, relative and absolute variations of cTn in a large population of asymptomatic hemodialysis patients were established during a period of 15 months. Patients were stratified according to their history of coronary artery disease (CAD). An intra-individual long term variation of 23% for cTroponin I (cTnI) and 12% for cTroponin T (cTnT) was found for patients without a history of CAD. The corresponding reference change values (RCVs) were 69% and 39% respectively. For patients with a history of CAD this variation was 29% for cTnI and 10% for cTnT, with RCVs of 86% and 35% respectively. During follow up, 27 HD patients developed an acute myocardial infarction (AMI). During these events, irrespective of CAD history, cTnI increased>172% and cTnT increased>97% above baseline cTn as measured during clinically stable periods three months separate to the event. Therefore, if a HD patient has symptoms of an acute event and a cTn increase that exceeds the RCVs described here, AMI may be suspected. If the troponin increase exceeds 172% for cTnI or 97% for cTnT, AMI is likely. PMID- 26874044 TI - Scouting new sigma receptor ligands: Synthesis, pharmacological evaluation and molecular modeling of 1,3-dioxolane-based structures and derivatives. AB - Herein we report the synthesis and biological activity of new sigma receptor (sigmaR) ligands obtained by combining different substituted five-membered heterocyclic rings with appropriate sigmaR pharmacophoric amines. Radioligand binding assay, performed on guinea pig brain membranes, identified 25b (1-(1,4 dioxaspiro[4.5]decan-2-ylmethyl)-4-benzylpiperazine) as the most interesting compound of the series, displaying high affinity and selectivity for sigma1R (pKisigma1 = 9.13; sigma1/sigma2 = 47). The ability of 25b to modulate the analgesic effect of the kappa agonist (-)-U-50,488H and MU agonist morphine was evaluated in vivo by radiant heat tail-flick test. It exhibited anti-opioid effects on both kappa and MU receptor-mediated analgesia, suggesting an agonistic behavior at sigma1R. Docking studies were performed on the theoretical sigma1R homology model. The present work represents a new starting point for the design of more potent and selective sigma1R ligands. PMID- 26874045 TI - The epigenetics of tumour initiation: cancer stem cells and their chromatin. AB - Cancer stem cells (CSCs) have been identified in various tumours and are defined by their potential to initiate tumours upon transplantation, self-renew and reconstitute tumour heterogeneity. Modifications of the epigenome can favour tumour initiation by affecting genome integrity, DNA repair and tumour cell plasticity. Importantly, an in-depth understanding of the epigenomic alterations underlying neoplastic transformation may open new avenues for chromatin-targeted cancer treatment, as these epigenetic changes could be inherently more amenable to inhibition and reversal than hard-wired genomic alterations. Here we discuss how CSC function is affected by chromatin state and epigenomic instability. PMID- 26874046 TI - Household air pollution and lung cancer risk among never-smokers in Nepal. AB - More than half of the global population relies on biomass fuels (wood, charcoal, crop residue, dung) for cooking and/or heating purposes. Household air pollution (HAP) resulting from the use of these solid fuels is of particular concern, given the overall prevalence as well as the intensity of exposure and the range of potential adverse health outcomes. Long term exposure to HAP is a major public health concern, particularly among women and children in low and middle income countries. In this study, we investigated the association between exposure to HAP resulting from combustion of biomass and lung cancer risk among Nepalese population. Using a hospital-based case-control study (2009-2012), we recruited 606 lung cancer cases and 606 healthy controls matched on age (+/-5 years), gender, and geographical residence. We used unconditional logistic regression to compute odds ratios (ORs) and 95% Confidence Intervals (95% CI) for lung cancer risk associated with HAP exposures, adjusting for potential confounders (tobacco use, TB status, SES, age, gender, ethnicity, and exposure to second hand smoke. In our overall analysis, we observed increased risk of lung cancer among those who were exposed to HAPs (OR: 1.77, 95% CI: 1.00-3.14). A more detailed analysis stratified by smoking status showed considerably higher risk of lung cancer associated with increasing duration of exposure to HAP from biomass combustion, with evidence of a borderline exposure-response relationship (Ptrend=0.05) that was more pronounced among never-smokers (Ptrend=0.01). Our results suggest that chronic exposure to HAP resulting from biomass combustion is associated with increased lung cancer risk, particularly among never-smokers in Nepal. PMID- 26874047 TI - In vitro short-term exposure to air pollution PM2.5-0.3 induced cell cycle alterations and genetic instability in a human lung cell coculture model. AB - Although its adverse health effects of air pollution particulate matter (PM2.5) are well-documented and often related to oxidative stress and pro-inflammatory response, recent evidence support the role of the remodeling of the airway epithelium involving the regulation of cell death processes. Hence, the overarching goals of the present study were to use an in vitro coculture model, based on human AM and L132 cells to study the possible alteration of TP53-RB gene signaling pathways (i.e. cell cycle phases, gene expression of TP53, BCL2, BAX, P21, CCND1, and RB, and protein concentrations of their active forms), and genetic instability (i.e. LOH and/or MSI) in the PM2.5-0.3-exposed coculture model. PM2.5-0.3 exposure of human AM from the coculture model induced marked cell cycle alterations after 24h, as shown by increased numbers of L132 cells in subG1 and S+G2 cell cycle phases, indicating apoptosis and proliferation. Accordingly, activation of the TP53-RB gene signaling pathways after the coculture model exposure to PM2.5-0.3 was reported in the L132 cells. Exposure of human AM from the coculture model to PM2.5-0.3 resulted in MS alterations in 3p chromosome multiple critical regions in L132 cell population. Hence, in vitro short-term exposure of the coculture model to PM2.5-0.3 induced cell cycle alterations relying on the sequential occurrence of molecular abnormalities from TP53-RB gene signaling pathway activation and genetic instability. PMID- 26874048 TI - Country-specific estimates of the incidence of intellectual disability associated with prenatal exposure to methylmercury. AB - This paper describes country-specific estimates of the incidence of intellectual disability in children associated with prenatal exposure to methylmercury. A systematic review was undertaken to identify country-specific data on hair mercury concentrations in women of reproductive age. A variety of approaches were used to estimate biomarker concentrations for countries lacking such data. A dose effect relationship derived on the basis of the data from three large prospective studies relating prenatal methylmercury exposure to IQ in children was used to estimate the country-specific incidences of mild, moderate, severe, and profound intellectual disability in children as a result of prenatal methylmercury exposure. The incidence of methylmercury-associated mild intellectual disability (IQ scores 50-70) varied nearly 40-fold across countries, with the greatest incidences generally in countries that are islands or that are coastal. Countries with high birth rates and greater consumption of foods that contribute most to methylmercury intake in humans (seafood, rice) can be expected to make the largest contributions to the worldwide burden of disease associated with methylmercury. The assumptions and limitations of the estimates are discussed. PMID- 26874049 TI - Technical note: Efficient removal of a PCR inhibitory agent (vivianite) found on excavated bones. AB - During a rescue excavation in October 2011, archaeologists discovered a mass grave with 10 individuals. The skeletons should belong to victims of the battle of Reichenberg between the Austrian and Prussian armies on April 21, 1757. Several bones of the skeletons were covered with a blue colored encrustation. Initial DNA analysis failed due to strong inhibition. Chemical analysis of the bluish encrustation indicated the presence of the iron phosphate mineral vivianite (Fe3(PO4)2.(H2O)8). This technical note describes a novel procedure for the removal of this inhibitory substance. PMID- 26874050 TI - Analysis of gunshot residues as trace in nasal mucus by GFAAS. AB - When a gun is fired, the majority of gunshot residues are deposited on the shooter's hands. But these residues disappear through contact with surfaces or washing. Therefore, the maximum time frame to find GSR on a suspect's hands is 8h. The mucus, inside of a nostril, forms a surface layer where they are trapped foreign particles. In this way, mucus inside of a gunshot suspect's nostrils could act like an adhesive medium to stick on it gaseous particles from a gunshot. In this study, the presence of GSR in nasal mucus and its residence time is examined. A new procedure for the sampling of possible gunshot residue accumulated in the nasal mucus is designed. Samples are taken with cotton swabs moistened with a solution of EDTA and, after an acid digestion, are analysed by graphite furnace atomic absorption spectrometry. In addition, samples of hands are taken for comparison purposes. GSR recovery has been successful. The concentration of GSR in nasal mucus is found to be lower than on the hands, but with a longer residence time. Thus, it is possible to expand the sampling time of a suspect also, as nasal mucus cannot be contaminated by handling weapons. PMID- 26874051 TI - Developing the use of Structure-from-Motion in mass grave documentation. AB - Methods for mass-grave documentation have changed markedly since the first forensic investigations nearly 70 years ago. Recently, however, there has been little advancement in developing new and better methodology, especially when compared to other forensic disciplines and even within traditional archaeology. This paper proposes a new approach, using 3D modelling for the documentation and eventual analysis of mass-graves. Structure-from-Motion (SfM), which creates digital 3D models from a set of still photographs, was tested on a small, simulated mass grave. The results of this test suggest that the method offers resolution previously unavailable to mass-grave investigators, and facilitates stronger analytical potential than the more traditional methods. Further tests are needed to validate these methods, but these initial findings are promising and their application could enhance our knowledge of mass grave dynamics. PMID- 26874052 TI - Use of atomic force microscopy in the forensic application of chronological order of toners and stamping inks in questioned documents. AB - This paper describes the application of the atomic force microscopy (AFM) as a nano-indentation method and introduces a new method of identifying the chronological order of the application of the toner and stamping ink on the surface of documents by removing either of them. Various toners were used as samples for the AFM nano-indentation method. The chronological order of the application of the toner and stamping ink with either the toner placed over the stamping ink or the stamping ink placed over the toner, could be identified, regardless of the kinds of toners made by various companies. This paper provides the new approach for physically removing the toner and checking the material below it to identify questioned documents, which allows the method to be used to appraise documents forensically. Blind testing has shown that the method to analyze the chronological order of toner-printed documents and the seal stamping on them could accurately identify the order in all samples, while minimizing damage to the samples. PMID- 26874053 TI - Internal switches modulating electron tunneling currents in respiratory complex III. AB - In different X-ray crystal structures of bc1 complex, some of the key residues of electron tunneling pathways are observed in different conformations; here we examine their relative importance in modulating electron transfer and propose their possible gating function in the Q-cycle. The study includes inter-monomeric electron transfer; here we provide atomistic details of the reaction, and discuss the possible roles of inter-monomeric electronic communication in bc(1) complex. Binding of natural ligands or inhibitors leads to local conformational changes which propagate through protein and control the conformation of key residues involved in the electron tunneling pathways. Aromatic-aromatic interactions are highly utilized in the communication network since the key residues are aromatic in nature. The calculations show that there is a substantial change of the electron transfer rates between different redox pairs depending on the different conformations acquired by the key residues of the complex. PMID- 26874054 TI - The switching mechanism of the mitochondrial ADP/ATP carrier explored by free energy landscapes. AB - The ADP/ATP carrier (AAC) of mitochondria has been an early example for elucidating the transport mechanism alternating between the external (c-) and internal (m-) states (M. Klingenberg, Biochim. Biophys. Acta 1778 (2008) 1978 2021). An atomic resolution crystal structure of AAC is available only for the c state featuring a three repeat transmembrane domain structure. Modeling of transport mechanism remained hypothetical for want of an atomic structure of the m-state. Previous molecular dynamics studies simulated the binding of ADP or ATP to the AAC remaining in the c-state. Here, a full description of the AAC switching from the c- to the m-state is reported using well-tempered metadynamics simulations. Free-energy landscapes of the entire translocation from the c- to the m-state, based on the gyration radii of the c- and m-gates and of the center of mass, were generated. The simulations revealed three free-energy basins attributed to the c-, intermediate- and m-states separated by activation barriers. These simulations were performed with the empty and with the ADP- and ATP-loaded AAC as well as with the poorly transported AMP and guanine nucleotides, showing in the free energy landscapes that ADP and ATP lowered the activation free-energy barriers more than the other substrates. Upon binding AMP and guanine nucleotides a deeper free-energy level stabilized the intermediate state of the AAC2 hampering the transition to the m-state. The structures of the substrate binding sites in the different states are described producing a full picture of the translocation events in the AAC. PMID- 26874055 TI - Accuracy of emotion labeling in children of parents diagnosed with bipolar disorder. AB - BACKGROUND: Emotion labeling deficits have been posited as an endophenotype for bipolar disorder (BD) as they have been observed in both patients and their first degree relatives. It remains unclear whether these deficits exist secondary to the development of psychiatric symptoms or whether they can be attributed to risk for psychopathology. To explore this, we investigated emotion processing in symptomatic and asymptomatic high-risk bipolar offspring (HRO) and healthy children of healthy parents (HCO). METHODS: Symptomatic (n:18, age: 13.8 +/- 2.6 years, 44% female) and asymptomatic (n:12, age: 12.8 +/- 3.0 years, 42% female) HRO and age- and sex-matched HCO (n:20, age: 13.3 +/- 2.5 years, 45% female) performed an emotion-labeling task. Total number of errors, emotion category and intensity of emotion error scores were compared. Correlations between total error scores and symptom severity were also investigated. RESULTS: Compared to HCO, both HRO groups made more errors on the adult face task (pcor=0.014). The HRO group were 2.3 times [90%CI:0.9-6.3] more likely and 4.3 times [90%CI:1.3-14.3] more likely to make errors on sad and angry faces, respectively. With the exception of sad face type errors, we observed no significant differences in error patterns between symptomatic and asymptomatic HRO, and no correlations between symptom severity and total number of errors. LIMITATIONS: This study was cross-sectional in design, limiting our ability to infer trajectories or heritability of these deficits. CONCLUSIONS: This study provides further support for emotion labeling deficits as a candidate endophenotype for BD. Our study also suggests these deficits are not attributable to the presence of psychiatric symptoms. PMID- 26874056 TI - Natural variability in Drosophila larval and pupal NaCl tolerance. AB - The regulation of NaCl is essential for the maintenance of cellular tonicity and functionality, and excessive salt exposure has many adverse effects. The fruit fly, Drosophila melanogaster, is a good osmoregulator and some strains can survive on media with very low or high NaCl content. Previous analyses of mutant alleles have implicated various stress signaling cascades in NaCl sensitivity or tolerance; however, the genes influencing natural variability of NaCl tolerance remain for the most part unknown. Here, we use two approaches to investigate natural variation in D. melanogaster NaCl tolerance. We describe four D. melanogaster lines that were selected for different degrees of NaCl tolerance, and present data on their survival, development, and pupation position when raised on varying NaCl concentrations. After finding evidence for natural variation in salt tolerance, we present the results of Quantitative Trait Loci (QTL) mapping of natural variation in larval and pupal NaCl tolerance, and identify different genomic regions associated with NaCl tolerance during larval and pupal development. PMID- 26874057 TI - Large scale distribution of dioxins, PCBs, heavy metals, PAH-metabolites and radionuclides in cod (Gadus morhua) from the North Atlantic and its adjacent seas. AB - Regarding cod as sea food for human consumption and as bio indicator of the marine eco system, this study is the first approach to combine the analysis of organic and inorganic contaminants and radionuclides in cod muscle as well as PCDD/Fs and dl-PCBs in its livers from the same fishing areas. Concentrations of 1-hydroxypyrene, PCDD/Fs, PCBs, cesium-137 (Cs-137), cadmium and lead were determined in individual or pooled samples over a wide geographic area, including Greenland Seas, Barents Sea, North and Baltic Sea. Highest concentrations were found in samples from the Baltic Sea, lowest in the pristine areas of the Barents Sea and Greenland. Levels of contaminants in cod muscle were found to be far below the established EU maximum levels (ML), regardless of which fishing grounds. In contrast to this, most cod liver samples from the North and Baltic Sea showed PCDD/F and PCB contents exceeding the ML. In addition, new background assessment criteria (BAC) for 1-hydroxypyrene in cod of 4.6 ng mL(-1) bile and for Cs-137 a BAC of 0.16 Bq kg(-1) wet weight are proposed to be included in the European Marine Strategy Framework Directive for cod from the Northeast Atlantic. PMID- 26874058 TI - Hepatic effects of the clomazone herbicide in both its free form and associated with chitosan-alginate nanoparticles in bullfrog tadpoles. AB - The use of agrochemicals in agriculture is intense and most of them could be carried out to aquatic environment. Nevertheless, there are only few studies that assess the effects of these xenobiotics on amphibians. Clomazone is an herbicide widely used in rice fields, where amphibian species live. Thus, those species may be threatened by non-target exposure. However, nanoparticles are being developed to be used as a carrier system for the agrochemicals. Such nanoparticles release the herbicide in a modified way, and are considered to be more efficient and less harmful to the environment. The aim of this study was to comparatively evaluate the effect of clomazone in its free form and associated with nanoparticles, in the liver of bullfrog tadpoles (Lithobates catesbeianus) when submitted to acute exposure for 96 h. According to semi-quantitative analysis, there was an increase in the frequency of melanomacrophage centres, in the accumulation of eosinophils and in lipidosis in the liver of experimental groups exposed to clomazone - in its free form and associated with nanoparticles - in comparison with the control group, and the nanotoxicity of chitosan-alginate nanoparticles. The increase of melanomacrophage centres in all exposed groups was significant (P < 0.0001) in comparison to control group. Therefore, the results of this research have shown that exposure to sublethal doses of the herbicide and nanoparticles triggered hepatic responses. Moreover, these results provided important data about the effect of the clomazone herbicide and organic nanoparticles, which act as carriers of agrochemicals, on the bullfrog tadpole liver. PMID- 26874059 TI - Determination of glucuronide conjugates of hydroxyl triphenyl phosphate (OH-TPHP) metabolites in human urine and its use as a biomarker of TPHP exposure. AB - In vitro studies using avian hepatocytes or human liver microsomes suggest that hydroxylation is an important pathway in the metabolism of triphenyl phosphate (TPHP), a chemical used as a flame retardant and plasticizer. TPHP metabolism can lead to the formation of para(p)- and meta(m)-hydroxyl-(OH-)TPHP products as well as their glucuronide conjugates. To determine whether the TPHP hydroxylation and depuration pathway also occurs in vivo in humans, the present study developed a sensitive method for quantification of p- and m-OH-TPHP glucuronides in human urine samples. In n = 1 pooled urine sample and n = 12 individual urine samples collected from four human volunteers from Ottawa (ON, Canada), p- and m-OH-TPHP glucuronides were detectable in 13 and 9 of the 13 analyzed samples and at concentrations ranging from =65 with nonmetastatic DTC. Patients undergoing neck dissection >6 months after their initial diagnosis were considered to have regional recurrent disease. We compared overall survival (OS) and cause-specific survival (CSS) for patients with recurrent disease versus a matched cohort of patients with non-recurrent DTC. RESULTS: Of 6235 patients, 143 had treatment defined recurrent disease. Patients with recurrent disease had inferior OS (p < .01) and CSS (p < .01). Multivariate analysis demonstrated that recurrent disease was independently associated with inferior 10-year OS (hazard ratio [HR] = 1.75; p < .01) and CSS (HR = 3.05; p < .01). CONCLUSION: Regional recurrence of DTC may negatively impact OS and CSS in patients >=65 years old. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 919-924, 2016. PMID- 26874074 TI - Radiation safety for anaesthesia providers in the orthopaedic operating room. AB - In many orthopaedic operating rooms, anaesthesia providers routinely wear lead aprons for protection from radiation, but some studies have questioned whether this is needed. We conducted a systematic review to identify studies that measured the amount of radiation that anaesthetists were exposed to in the orthopaedic operating room. Multiple studies have shown that at 1.5 m from the source of radiation, anaesthetists received no radiation, or amounts so small that a person would have to be present in an unreasonable number of operations to receive cumulative doses of any significance. Radiation doses at this distance were often at the limits of the sensitivity of the measuring dosimeter. We question the need to wear lead protection for anaesthesia providers who are routinely at 1.5 m or a greater distance from standard fluoroscopy units. PMID- 26874075 TI - Should the Integrity of Mucosa Be Considered in Endoscopic Resection of Gastric Submucosal Tumors? PMID- 26874077 TI - Concordance of the location of the innervation zone of the tibialis anterior muscle using voluntary and imposed contractions by electrostimulation. AB - BACKGROUND: The innervation zone (IZ) corresponds to the location of the neuromuscular junctions. Its location can be determined by using arranged surface linear electrode arrays. Typically, voluntary muscle contractions (VC) are used in this method. However, it also may be necessary to locate the IZ under clinical conditions such as spasticity, in which this type of contraction is difficult to perform. Therefore, contractions imposed by electrostimulation (ES) can be an alternative. There is little background comparing the locations of IZ obtained by two different types of contractions. OBJECTIVE: Evaluate the concordance between using voluntary and imposed contractions from electrostimulation in order to determine the location of the innervation zone of the tibialis anterior muscle in healthy volunteers. METHODS: The tibialis anterior (TA) muscle of sixteen volunteers (men: 8; women: 8; age: 22.1+/-1.4years, weight: 61.6+/-7.5kg, height: 167.1+/-7.5cm) were evaluated using a linear electrode array. The IZ of the TA muscle was located using two types of muscle contractions, voluntary (10% MVC) and imposed contractions by ES. The concordance between both conditions was evaluated using the Bland-Altman method and the concordance correlation coefficient (CCC). The analyses were applied to the absolute and relative positions to the length of an anatomical landmark frame. RESULTS: CCC for absolute position was 0.98 (p<0.0001, 95% CI [0.98-1.00], and CCC for relative positions also was 0.98 (p<0.0001, 95% CI [0.97-1.00]). The Bland-Altman analysis for absolute data showed an average difference of -0.63mm (SD: 4.1). Whereas, for adjusted data, the average difference was -0.20% (SD: 1.2). The power of the results, based on absolute data, was 98%, whereas for relative data, 82%. CONCLUSION: In healthy volunteers, there was a substantially concordance between the location of the IZ of the TA muscle derived from using contractions imposed by ES and the location derived from using VC. PMID- 26874078 TI - Neuromuscular response amplitude to mechanical stimulation using large-array surface electromyography in participants with and without chronic low back pain. AB - PURPOSE: The present study aimed to compare the neuromuscular response under various mechanical stimulations of the lumbar spine in participants with and without chronic low back pain (cLBP). METHODS: Four mechanical stimulations, characterized by forces ranging from 75 to 225N, were delivered using a servo controlled linear actuator motor to the L3 spinous process of 25 healthy participants and 26 participants with cLBP. Lumbar neuromuscular responses were recorded using 64-electrodes large surface electromyography arrays. Between-group differences in the dose-response relationship (neuromuscular response amplitude according to each force level) were assessed using mixed model ANOVAs. RESULTS: No differences between groups were shown (all p values>.05). A significant linear relationship was observed between forces and neuromuscular response amplitudes (p<.001) indicating an increase in response amplitudes with increasing stimulation force. Responses were observed throughout the lumbar region with highest response amplitudes in the vicinity of the contacted vertebra. CONCLUSION: The neuromuscular response amplitude triggered by localized lumbar mechanical stimulations does not differ between participants with and without cLBP. Moreover, even though stimulations were delivered at specific spinal segment, a neuromuscular response, although rapidly decreasing, was observed in areas distant from the contact site. PMID- 26874076 TI - Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. AB - BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator activated receptor-alpha and peroxisome proliferator-activated receptor-delta. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH). METHODS: Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score. RESULTS: In intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; 95% confidence interval: 1.02-5.24; P = .045), based on a post-hoc analysis for the modified definition. In post-hoc analyses of patients with nonalcoholic fatty liver disease activity score >=4 (n = 234), elafibranor 120 mg resolved NASH in larger proportions of patients than placebo based on the protocol definition (20% vs 11%; odds ratio = 3.16; 95% confidence interval: 1.22-8.13; P = .018) and the modified definitions (19% vs 9%; odds ratio = 3.52; 95% confidence interval: 1.32-9.40; P = .013). Patients with NASH resolution after receiving elafibranor 120 mg had reduced liver fibrosis stages compared with those without NASH resolution (mean reduction of 0.65 +/- 0.61 in responders for the primary outcome vs an increase of 0.10 +/- 0.98 in nonresponders; P < .001). Liver enzymes, lipids, glucose profiles, and markers of systemic inflammation were significantly reduced in the elafibranor 120-mg group vs the placebo group. Elafibranor was well tolerated and did not cause weight gain or cardiac events, but did produce a mild, reversible increase in serum creatinine (effect size vs placebo: increase of 4.31 +/- 1.19 MUmol/L; P < .001). CONCLUSIONS: A post-hoc analysis of data from trial of patients with NASH showed that elafibranor (120 mg/d for 1 year) resolved NASH without fibrosis worsening, based on a modified definition, in the intention-to-treat analysis and in patients with moderate or severe NASH. However, the predefined end point was not met in the intention to treat population. Elafibranor was well tolerated and improved patients' cardiometabolic risk profile. ClinicalTrials.gov number: NCT01694849. PMID- 26874080 TI - Perceived discrimination and poor health: Accounting for self-blame complicates a well-established relationship. AB - Past research has reliably demonstrated that both perceiving oneself as a target of discrimination and a tendency to blame negative events on oneself undermine psychological and physical health. These two literatures, however, have evolved largely independently of one another. The present research sought to develop a deeper understanding of the health effects of perceived discrimination by taking into account the relationship between perceived discrimination and self-blame. In two correlational studies, we examined perceived ethnic-based discrimination, self-blame, and psychological and physical health among White and ethnic minority adults residing in the United States. Contrary to the hypothesis that attributing negative events to discrimination leads to the discounting of self-blame, perceived discrimination and self-blame were positively related. Replicating past research, perceived discrimination was negatively related to health when examined as an independent predictor. When perceived discrimination and self-blame were examined as simultaneous predictors of health, however, the negative health effects of perceived discrimination were weakened. Furthermore, an alternative model revealed that perceived discrimination indirectly predicted decreased health through increased self-blame. The present findings highlight the importance of taking self-blame into account when assessing and interpreting the negative health effects of perceived discrimination. PMID- 26874079 TI - Human GBP1 does not localize to pathogen vacuoles but restricts Toxoplasma gondii. AB - Guanylate binding proteins (GBPs) are a family of large interferon-inducible GTPases that are transcriptionally upregulated upon infection with intracellular pathogens. Murine GBPs (mGBPs) including mGBP1 and 2 localize to and disrupt pathogen-containing vacuoles (PVs) resulting in the cell-autonomous clearing or innate immune detection of PV-resident pathogens. Human GBPs (hGBPs) are known to exert antiviral host defense and activate the NLRP3 inflammasome, but it is unclear whether hGBPs can directly recognize and control intravacuolar pathogens. Here, we report that endogenous or ectopically expressed hGBP1 fails to associate with PVs formed in human cells by the bacterial pathogens Chlamydia trachomatis or Salmonella typhimurium or the protozoan pathogen Toxoplasma gondii. While we find that hGBP1 expression has no discernible effect on intracellular replication of C. trachomatis and S. typhimurium, we observed enhanced early Toxoplasma replication in CRISPR hGBP1-deleted human epithelial cells. We thus identified a novel role for hGBP1 in cell-autonomous immunity that is independent of PV translocation, as observed for mGBPs. This study highlights fundamental differences between human and murine GBPs and underlines the need to study the functions of GBPs at cellular locations away from PVs. PMID- 26874082 TI - A single adaptive point mutation in Japanese encephalitis virus capsid is sufficient to render the virus as a stable vector for gene delivery. AB - Japanese encephalitis virus (JEV) is a neurotropic flavivirus that has broad range of hosts. Stable JEV vector has not been reported yet. Here, we constructed a JEV-EGFP by inserting a fragment of C38 (the N-terminal 38 amino acids of capsid)-EGFP-FMDV2A into the junction between 5'UTR and the N-terminus of capsid gene. An adaptive nucleotide mutation T45G (location at the N-terminus of capsid gene), resulting in an amino acid change from asparagine to lysine (N15K), was identified by genome sequencing. It stabilized the vector and enlarged the virion. The stabilizing effect might be general because it is also stable when EGFP was replaced with another marker, SNAP. A model was proposed for this stabilization effect based on previously published and our data. This finding may be used to construct various JEV-based stable delivery systems for virological studies and neural circuit tracing. PMID- 26874081 TI - Evidence of social network influence on multiple HIV risk behaviors and normative beliefs among young Tanzanian men. AB - Research on network-level influences on HIV risk behaviors among young men in sub Saharan Africa is severely lacking. One significant gap in the literature that may provide direction for future research with this population is understanding the degree to which various HIV risk behaviors and normative beliefs cluster within men's social networks. Such research may help us understand which HIV related norms and behaviors have the greatest potential to be changed through social influence. Additionally, few network-based studies have described the structure of social networks of young men in sub-Saharan Africa. Understanding the structure of men's peer networks may motivate future research examining the ways in which network structures shape the spread of information, adoption of norms, and diffusion of behaviors. We contribute to filling these gaps by using social network analysis and multilevel modeling to describe a unique dataset of mostly young men (n = 1249 men and 242 women) nested within 59 urban social networks in Dar es Salaam, Tanzania. We examine the means, ranges, and clustering of men's HIV-related normative beliefs and behaviors. Networks in this urban setting varied substantially in both composition and structure and a large proportion of men engaged in risky behaviors including inconsistent condom use, sexual partner concurrency, and intimate partner violence perpetration. We found significant clustering of normative beliefs and risk behaviors within these men's social networks. Specifically, network membership explained between 5.78 and 7.17% of variance in men's normative beliefs and between 1.93 and 15.79% of variance in risk behaviors. Our results suggest that social networks are important socialization sites for young men and may influence the adoption of norms and behaviors. We conclude by calling for more research on men's social networks in Sub-Saharan Africa and map out several areas of future inquiry. PMID- 26874083 TI - Ebola virus disease diagnosis by real-time RT-PCR: A comparative study of 11 different procedures. AB - BACKGROUND: The diagnosis of Ebola virus disease relies on the detection of viral RNA in blood by real-time reverse-transcription PCR. While several of these assays were developed during the unprecedented 2013-2015 Ebola virus disease outbreak in West Africa, few were applied in the field. OBJECTIVES: To compare technical performances and practical aspects of 11 Ebola virus real-time reverse transcription PCR procedures. STUDY DESIGN: We selected the most promising assays using serial dilutions of culture-derived Ebola virus RNA and determined their analytical sensitivity and potential range of quantification using quantified in vitro transcribed RNA; viral load values in the serum of an Ebola virus disease patient obtained with these assays were reported. Finally, ease of use and turnaround times of these kits were evaluated. RESULTS: Commercial assays were at least as sensitive as in-house tests. Five of the former (Altona, Roche, Fast track Diagnostics, and Life Technologies) were selected for further evaluation. Despite differences in analytical sensitivity and limits of quantification, all of them were suitable for Ebola virus diagnosis and viral load estimation. The Lifetech Lyophilized Ebola Virus (Zaire 2014) assay (Life Technologies) appeared particularly promising, displaying the highest analytical sensitivity and shortest turnaround time, in addition to requiring no reagent freezing. CONCLUSIONS: Commercial kits were at least as sensitive as in-house tests and potentially easier to use in the field than the latter. This qualitative comparison of real-time reverse transcription PCR assays may serve as a basis for the design of future Ebola virus disease diagnostics. PMID- 26874084 TI - Effects of pre-slaughter diet/management system and fasting period on physiological indicators and meat quality traits of lambs. AB - This study determined the effects of pre-slaughter diet/management system on blood and rumen parameters and meat-quality traits of Norduz lambs. Eighty lambs were divided into two groups according to diet (AH: alfalfa hay; BAH: alfalfa supplemented with 500 g/head barley) for 21 days. Following this period, lambs from each group were distributed among four groups according to pre-slaughter fasting period as 0, 12, 24 or 48 h. Cortisol concentrations were found to be significantly higher in the 24 h and 48 h groups when compared to the 0 h group (p<0.01). Diet and fasting period had limited effect on muscle glycogen content and ultimate pH.L*, WHC and moisture decreased in line with increases in the fasting period (p<0.01). In conclusion, carcass conformation and some meat quality traits were better in BAH lambs. Fasting had a negative effect on some meat quality parameters, with significant increases in some physiological stress indicators after fasting periods of 24 h or longer. PMID- 26874085 TI - Feed efficiency indexes and their relationships with carcass, non-carcass and meat quality traits in Nellore steers. AB - Five hundred and seventy-five Nellore steers were evaluated for residual feed intake and residual feed intake and gain and their relationships between carcass, non-carcass and meat quality traits. RFI was measured by the difference between observed and predicted dry matter intake and RIG was obtained by the sum of 1*RFI and residual gain. Efficient and inefficient animals were classified adopting +/-0.5 standard deviations from RFI and RIG mean. A mixed model was used including RFI or RIG and contemporary group as fixed effects, initial age as covariate and sire and experimental period as random effects, testing the significance of the regression slope for each evaluated trait. RIG was positively related to longissimus muscle area. Efficient-RFI animals had lower liver and internal fat proportions compared to inefficient-RFI animals. Efficient-RFI and efficient-RIG animals had 11.8% and 11.2% lower extracted intramuscular fat, compared to inefficient-RFI and inefficient-RIG animals, respectively. Efficient RFI animals had tougher meat compared to inefficient-RFI animals. PMID- 26874086 TI - Pre-slaughter sound levels and pre-slaughter handling from loading at the farm till slaughter influence pork quality. AB - This study investigates the relationship between sound levels, pre-slaughter handling during loading and pork quality. Pre-slaughter variables were investigated from loading till slaughter. A total of 3213 pigs were measured 30 min post-mortem for pH(30LT) (M. Longissimus thoracis). First, a sound level model for the risk to develop PSE meat was established. The difference in maximum and mean sound level during loading, mean sound level during lairage and mean sound level prior to stunning remained significant within the model. This indicated that sound levels during loading had a significant added value to former sound models. Moreover, this study completed the global classification checklist (Vermeulen et al., 2015a) by developing a linear mixed model for pH(30LT) and PSE prevalence, with the difference in maximum and mean sound level measured during loading, the feed withdrawal period and the difference in temperature during loading and lairage. Hence, this study provided new insights over previous research where loading procedures were not included. PMID- 26874087 TI - A study on the tensile properties of silicone rubber/polypropylene fibers/silica hybrid nanocomposites. AB - Metacarpophalangeal joint implants have been usually made of silicone rubber. In the current study, silica nano particles and polypropylene fibers were added to silicone rubber to improve silicone properties. The effect of the addition of silica nano particles and polypropylene fibers on the tensile behavior of the resultant composites were investigated. Composite samples with different content of PP fibers and Silica nano particles (i. e. 0, 1 and 2wt%) as well as the hybrid composite of silicone rubber with 1wt% SiO2 and 1wt% PP fiber were prepared. Tensile tests were done at constant cross head speed. To study the body fluid effect on the mechanical properties of silicone rubber composites, samples soaked in simulated body fluid (SBF) at 37 degrees C were also tested. The morphology of the samples were studied by scanning electron microscope. Results of analysis revealed that an increase in PP fibers and silica nano particles content to 2wt%, increases the tensile strength of silicone rubber of about 75% and 42% respectively. It was found out that the strength of the samples decreases after being soaked in simulated body fluid, though composites with PP fibers as the reinforcement showed less property degradation. PMID- 26874088 TI - Porous vitalium-base nano-composite for bone replacement: Fabrication, mechanical, and in vitro biological properties. AB - Porous nano-composites were successfully prepared on addition of 58S bioactive glass to Co-base alloy with porosities of 37.2-58.8% by the combination of milling, space-holder and powder metallurgy techniques. The results of X-ray diffraction analysis showed that induced strain during milling of the Co-base alloy powder and also isothermal heat treatment during sintering process led to HCP<->FCC phase transformation which affected mechanical properties of the samples during compression test. Field emission scanning electron microscopy images showed that despite the remaining 58S powder in nanometer size in the composite, there were micro-particles due to sintering at high temperature which led to two different apatite morphologies after immersion in simulated body fluid. Calculated elastic modulus and 0.2% proof strength from stress-strain curves of compression tests were in the range of 2.2-8.3GPa and 34-198MPa, respectively. In particular, the mechanical properties of sample with 37.2% were found to be similar to those of human cortical bone. Apatite formation which was identified by scanning electron microscopy (SEM), pH meter and Fourier-transform infrared spectroscopy (FTIR) analysis showed that it could successfully convert bioinert Co-base alloy to bioactive type by adding 58S bioglass nano-particles. SEM images of cell cultured on the porous nano-composite with 37.2% porosity showed that cells properly grew on the surface and inside the micro and macro pores. PMID- 26874089 TI - Correlation Between Femoral Neck Shaft Angle and Surgical Management in Trainees With Femoral Neck Stress Fractures. AB - The most common overuse injury leading to medical discharge of military recruits is a stress fracture. One of the high-risk stress fractures is of the lateral femoral neck which risks osteonecrosis of the femoral head, the need for arthroplasty and permanent disability. To prevent fracture progression early surgical intervention is recommended. Surgical repairs are performed in about 25% of cases of femoral neck stress fractures at military treatment facilities. Hip geometry is an important intrinsic risk for stress fractures. Loads in the average loading direction will not cause a fracture, but loads of extreme magnitude or extreme orientation may. The purpose of this study was to determine if, in the presence of femoral neck stress fracture, there is a correlation between femoral neck shaft angle, surgical treatment and outcomes. The results of this study suggest there is no correlation between return to full military duty rates, treatment, femoral neck shaft angle or fracture grade on MRI. Patients who underwent surgical fixation had greater fracture grade and pain than those that did not have surgery. Individuals who did not return to duty tended to have higher pain scores at initial evaluation. PMID- 26874090 TI - Observed Rates of Lower Extremity Stress Fractures After Implementation of the Army Physical Readiness Training Program at JBSA Fort Sam Houston. AB - Millions of dollars are lost each year to the US military in medical discharges from injuries sustained in the initial training of recruits. Most medical discharges in recruits are related to musculoskeletal overuse injuries, including stress fractures. Any strategies that can reduce injury rates are also likely to reduce rates of medical discharge. This study evaluated the Army Physical Readiness Training (PRT) program which was established to provide a method of physical fitness training that would reduce the number of preventable injuries. We conducted a retrospective study to evaluate the number of lower extremity stress fractures that were diagnosed in the 6 months prior to and 6 months following the implementation of the PRT program. Electronic medical records were queried for specific diagnoses of stress fractures to the pelvis, femoral neck, femoral shaft, tibia, fibula, tarsals and metatarsals. The observed number of diagnoses in each time period were compared using the chi2 method. Decrease was shown not only in the overall occurrence of stress fractures, but specifically in the occurrence of stress fractures of the femoral neck, femoral shaft, and tarsals. Our study was able to show a correlation between the PRT program and a decrease in the observed occurrence of lower extremity stress fractures. PMID- 26874091 TI - What Soldiers Know and Want to Know About Preventing Injuries: A Needs Survey Regarding a Key Threat to Readiness. PMID- 26874092 TI - Rhabdomyolysis in a Sickle Cell Trait Positive Active Duty Male Soldier. AB - Exertional rhabdomyolysis is a complication of sickle cell trait (SCT) likely first reported in the military population over 40 years ago. Although commonly a benign condition, numerous studies and case reports have identified SCT positive patients to be at increased risk for rhabdomyolysis, compartment syndrome and sudden cardiac death. We report a recent case of an SCT positive African American active duty male Soldier who suffered exertional rhabdomyolysis following an Army Physical Fitness Test. His course was complicated by acute renal failure requiring hemodialysis, and he eventually recovered renal function. The diagnosis was significantly delayed despite a typical clinical presentation and available SCT screening results. The case highlights the importance of the recognition of SCT as a risk factor for severe rhabdomyolysis, and suggests more must be done for an effective SCT screening program for the active duty military population. PMID- 26874093 TI - Hydration Status in US Military Officer Students. AB - Relocation from a cool to a hot climate is a frequent occurrence in military service. Acclimatization requires time and exposure to heat. Nonacclimatized individuals frequently consume inadequate fluid leading to hypohydration, which can quickly result in dehydration with increased risk of heat illness/injury. This descriptive cross-sectional study assessed the hydration status of 196 officers attending the US Army Medical Department's Officer Basic Course (67%) or Captain's Career Course (33%) in San Antonio, Texas, prior to taking the Army Physical Fitness Test (APFT). Consenting Soldiers provided a first morning void urine sample and demographic survey (age, rank, sex, previous geographic location, etc) prior to the APFT. Height, weight, and APFT event scores were collected from a subject-coded, APFT scorecard without personal information data. Binary logistic regression was performed to identify variables that contribute to predicting hypohydration status. The sample population was 54% male, a mean age of 30 years, 5.2 years of military service, and a mean body mass index of 25 kg/m2. Nearly one-third met the criteria for hypohydration (>=1.02 urine specific gravity). Soldiers who relocated from a cool environment within 9 days of taking the APFT had 2.1 higher odds of being hypohydrated compared with individuals who had resided in a hot environment for more than 9 days. Women had a 0.5 lower odds of being hypohydrated as compared to males. Significantly more Soldiers were hypohydrated on Monday compared to those tested on Tuesday (33% vs 16%, P=.004). Given these findings, the authors provided 5 recommendations to reduce the number of Soldiers exercising in a hypohydrated state. PMID- 26874094 TI - Muscle-related Disability Following Combat Injury Increases With Time. AB - BACKGROUND: Combat injuries are most often to the extremities, resulting in a majority of long term disabilities being of orthopaedic nature. Some injuries are expected to improve with time. The Army Physical Evaluation Board (PEB) gives consideration for conditions that may improve with further care by placing eligible patients on a temporary retirement list. While this may be appropriate for some conditions, injuries such as those to skeletal muscle can be irrecoverable. We aimed to examine combat injured subjects with known muscle injuries who were placed in temporary retirement status to determine if their muscle conditions improved. We hypothesized that muscle-related disability would not improve despite additional time for recovery. METHODS: The PEB results of 33 combat wounded service members were reviewed to determine what individuals were placed in temporary retirement status. We compared what muscle conditions were present at each PEB examination including the initial review, internal temporary retirement reexaminations, and the final adjudication. We also compared if the disability rating assigned to the muscle condition changed with time. FINDINGS: Eighteen of the 33 subjects were placed in temporary retirement status prior to their final retirement. None of the subjects experienced improvement in their muscle condition as measured by disability ratings. Seven subjects worsened while 9 subjects had muscle conditions recognized at their final disposition that were not recognized at initial exam. Two subjects have muscle disability ratings that were unchanged. CONCLUSIONS: While temporary retirement status provided opportunities for injured service members to experience additional improvement prior to permanent retirement, not all conditions can be expected to improve. This study demonstrates that the Army PEB ratings for muscle conditions did not improve despite additional recovery time being granted to the subjects on temporary retirement status. PMID- 26874095 TI - War and Rehabilitation: Occupational Therapy's Power to Transform Disability Into Ability. PMID- 26874096 TI - Center for the Intrepid: Providing Patients POWER. PMID- 26874097 TI - Implementation of a Transition of Care Coordinator at a Military Treatment Facility. AB - A patient's transition from the inpatient to the outpatient setting is complex and prone to medical errors. This subsequently increases patient morbidity and cost to the healthcare system. METHODS: Our quality improvement initiative used a licensed clinical social worker from within a Family Medicine residency clinic to serve as a Transitions of Care Coordinator (TOCC) with the goal of decreasing patient morbidity and system cost. RESULTS: The number of documented patient contacts by our primary care office in the postdischarge period increased significantly after implementation of the TOCC (3.1% vs 40.2%, P=.01). Pearson correlation during our postimplementation period suggested an inverse relationship between contact by a TOCC and emergency department (ED) and hospital utilization rates (r=-0.68, P=.05 and r=0.062, P=.005, respectively). However, the percentage of ED visits (11.9% vs 20.8%, P=.02) and hospital readmissions (5.6% vs 13.7%, P=.01) significantly increased overall between the pre-and postimplementation periods. CONCLUSIONS: The implementation of a TOCC within a military Family Medicine residency clinic significantly increased the frequency of ED visits and readmissions to the inpatient service for patients discharged from the Family Medicine inpatient service. PMID- 26874098 TI - Influence of Individual Determinants on Physical Activity at Work and During Leisure Time in Soldiers: A Prospective Surveillance Study. AB - Quantified physical activity is an important parameter for evaluating the risk of the incidence of internal and musculoskeletal disorders. The objective of this study was to evaluate the physical activity of German Soldiers on duty and during leisure time with regard to individual determinants and to evaluate if factors associated with the risk of the incidence of internal or musculoskeletal disorders are of relevance for physical activity. For this purpose, we conducted activity measurements on 169 subjects. The accelerometer-based activity sensor was worn for 7 consecutive days. The number of steps taken was evaluated as an activity marker.We observed that a high body mass index and a large waist circumference were associated with a low activity level. Women were found to be more active than men, particularly during leisure time. Personnel under 25 years of age were more physically active than those between 25 and 50 years of age. Subjects with underlying musculoskeletal disorders were less active than those who had internal disorders or were healthy. Men and overweight people run a higher risk of developing musculoskeletal and internal disorders. Health promotion should focus on raising the physical activity level with the aim of exerting a positive influence on the associated risk factors. PMID- 26874099 TI - GEHS Neurophysiological Classification System for Patients with Carpal Tunnel Syndrome. AB - BACKGROUND: Median neuropathy at or distal to the wrist or carpal tunnel syndrome (CTS) is one of a number of muscle, tendon, and nerve-related disorders that affect people performing intensive work with their hands. Following a thorough history and physical examination, electrophysiological examination including both nerve conduction studies (NCS) and electromyography (EMG) testing may be performed and currently serve as the reference standard for the diagnosis of CTS. The EMG and NCS exams should identify the peripheral nerve, specific location in the nerve pathway, involvement of sensory and/or motor axons, and the presence of myelinopathy and/or axonopathy neuropathic process. NEUROPHYSIOLOGICAL CLASSIFICATION SYSTEMS: Clinical electrophysiologists now have 2 neurophysiological classification systems for patients with CTS from which to choose when preparing their electrophysiological testing reports. The Bland (2000) and GEHS (2012) neurophysiological classification systems for patients with CTS are discussed. CASE STUDIES: Two case studies of patients with electrophysiological evidence of CTS are presented. Application and comparison of categorizations by the Bland and GEHS neurophysiological classification systems are incorporated into the presentation and discussion of these case studies. SUMMARY AND CLINICAL RELEVANCE: This article describes 2 neurophysiological classification systems for patients with CTS. The Bland system documents the distribution of patients with CTS on a scale based upon nerve conduction study findings, but it does not include any EMG findings in its grading scale. The GEHS neurophysiological classification system includes findings for both the NCS and EMG components of the electrophysiological examination. The GEHS classification system provides electrophysiological evidence of myelinopathy and/or axonopathy for patients with CTS. Additional research comparing the psychometric properties and prognostic utility of the Bland and GEHS neurophysiologic classifications is warranted. PMID- 26874100 TI - Q Fever. AB - Q fever is a significant infectious disease threat to US military personnel deployed in the Middle East. Its environmental stability, aerosol transmission, and animal reservoir make it a considerable risk for deployed troops due to its potential for weaponization and risk of natural infection. It presents as a flu like illness that responds promptly to antimicrobial therapy. Q fever should be suspected in patients presenting with a compatible febrile illness in an endemic area and especially if the individual has been exposed to livestock. Diagnosis is confirmed with serologic blood tests, but empiric therapy should be initiated when Q fever is considered. If left untreated, patients with acute Q fever can develop severe complications as well as chronic disease manifesting several months after the initial infection. PMID- 26874101 TI - Mobile Phone Health Applications for the Federal Sector. AB - PURPOSE: As the US healthcare system moves toward a mobile care model, mobile phones will play a significant role in the future of healthcare delivery. Today, 90% of American adults own a mobile phone and 64% own a smartphone, yet many healthcare organizations are only beginning to explore the opportunities in which mobile phones can improve and streamline care. METHOD: After searching Google Scholar, the Association for Computing Machinery Database, and PubMed for articles related to mobile phone health applications and cell phone text message health, we selected articles and studies related to the application of mobile phones in healthcare. From our initial review, we identified the potential application areas and continued to refine our search, identifying a total of 55 articles for additional review and analysis. FINDINGS: From the literature, we identified 3 main themes for mobile phone implementation in improving healthcare: primary, preventive, and population health. We recommend federal health leaders pursue the value and potential in these areas; not only because 90% of Americans already own mobile phones, but also because mobile phone integration can provide substantial access and potential cost savings. CONCLUSION: From the positive findings of multiple studies in primary, preventive, and population health, we propose a 5-year federal implementation plan to integrate mobile phone capabilities into federal healthcare delivery. Our proposal has the potential to improve access, reduce costs, and increase patient satisfaction, therefore changing the way the federal sector delivers healthcare by 2021. PMID- 26874102 TI - A Primary Care Telehealth Experience in a US Army Correctional Facility in Germany. AB - OBJECTIVE: To assess the feasibility of using telehealth (TH) equipment and infrastructure within the US Army's European Theater to evaluate and treat inmates with general medical complaints, and perform physicals and medical safety checks in a US Army Correctional Facility (CORFAC). METHODS AND MATERIALS: Synchronous TH encounters were performed using Polycom RealPresence software on providers' computers with high definition cameras on monitors at distant sites and PolyCom HDX9000 Practitioner Cart along with AMD Global Telemedicine devices at the originating site within the CORFAC. These devices included an AMD-2500 General Exam Camera, AMD Fiber optic Otoscope, and AMD Telephonic Stethoscope. Patient consent for TH was obtained, and they were seen in the Medical Dispensary with Army Medics presenting the patients to the providers via TH. RESULTS: From May 22, 2014, to January 12, 2015, a physician assistant, nurse practitioner, and 4 physicians completed 177 synchronous TH encounters primarily at a CORFAC in Mannheim, Germany. Of these 177 encounters, 114 were Special Housing Unit (SHU) safety checks and 63 encounters were for physicals, medication management, and a variety of medical complaints including acute infections, abdominal pain, and musculoskeletal and dermatological complaints. CONCLUSION: Synchronous TH was an effective option for the delivery of high quality routine medical care for minor illnesses, injuries, and other nonurgent conditions, as well as for general physicals and SHU checks in a correctional facility. Acceptance by providers and clinic staff was found to be high. Inmates were generally satisfied with their TH encounters. However, some inmates reported a preference to see providers in person, highlighting one of the challenges with acceptance of telehealth programs. PMID- 26874103 TI - Repair of a Gingival Fenestration Using an Acellular Dermal Matrix Allograft. AB - A case report illustrating the successful treatment of a gingival fenestration with an acellular dermal matrix (ADM) allograft. After 21/2 months of healing, the ADM was completely integrated into the soft tissues of the mandibular anterior gingiva with complete resolution of the gingival fenestration, resulting in excellent gingival esthetics. PMID- 26874104 TI - Reasons for Non-third Molar Extractions in a Military Population. PMID- 26874105 TI - Experimental and density functional theoretical study of the effects of Fenton's reaction on the degradation of Bisphenol A in a high voltage plasma reactor. AB - A novel electrical discharge plasma reactor configuration with and without iron ions was evaluated for the degradation of 0.02 mM Bisphenol A (BPA). The pseudo first-order reaction rate constant calculated for the plasma treatment of BPA with a stainless steel electrode in the presence of dissolved ferrous ion (Fe(2+)) salts (termed plasma/Fenton treatment) was higher than in the plasma treatment in the absence of iron salts. At the optimal ferrous ion concentration, longer plasma treatment times resulted in higher BPA degradation rates, likely due to increased hydroxyl (OH) radical concentration formed through the decomposition of H2O2. Replacing the stainless steel with a carbon steel grounded electrode resulted in the release of iron ions from the carbon steel thereby increasing the rate of BPA removal and eliminating the need for iron salts. After the plasma/Fenton treatment, >97% of the residual iron salts were removed by coagulation/flocculation/sedimentation. Byproduct identification coupled with density functional theory (DFT) calculations confirmed that OH radical attack on BPA's hydroxyl group is the primary pathway for byproduct formation. PMID- 26874106 TI - Fabricating a novel label-free aptasensor for acetamiprid by fluorescence resonance energy transfer between NH2-NaYF4: Yb, Ho@SiO2 and Au nanoparticles. AB - Rare earth-doped upconversion nanoparticles have promising potential in the field of pesticide detection because of their unique frequency upconverting capability and high detection sensitivity. This paper reports a novel aptamer-based nanosensor for acetamiprid detection using fluorescence resonance energy transfer (FRET) between NH2-NaYF4: Yb, Ho@SiO2 (UCNPs) and gold nanoparticles (GNPs). Herein, GNPs as acceptors efficiently quench the fluorescence of UCNPs and acetamiprid specifically interacts with acetamiprid binding aptamer (ABA), causing the conformation changes of ABA from random coil to hairpin structure. Accordingly, ABA no longer stabilizes the GNPs in salt solution, leading to the varying aggregation extent of GNPs. Thus, the fluorescence of UCNPs are proportionally recovered. Under the optimized conditions, the enhancement efficiency was observed to increase linearly with the concentration of acetamiprid from 50 nM to 1000 nM, resulting in a relatively low limit of 3.2 nM. Additionally, the aptasensor demonstrated high selectivity to similar structure pesticides such as imidacloprid and chlorpyrifos, and further confirmed its application capacity in adulterated tea samples. PMID- 26874107 TI - Low cost quantitative digital imaging as an alternative to qualitative in vivo bioassays for analysis of active aflatoxin B1. AB - Aflatoxin B1 (AFB1) producing fungi contaminate food and feed and are a major health concern. To minimize the sources and incidence of AFB1 illness there is a need to develop affordable, sensitive mobile devices for detection of active AFB1. In the present study we used a low cost fluorescence detector and describe two quantitative assays for detection of detoxified and active AFB1 demonstrating that AFB1 concentration can be measured as intensity of fluorescence. When the assay plate containing increasing concentrations of AFB1 is illuminated with a 366 nm ultraviolet lamp, AFB1 molecules absorb photons and emit blue light with peak wavelength of 432 nm. The fluorescence intensity increased in dose dependent manner. However, this method cannot distinguish between active AFB1 which poses a threat to health, and the detoxified AFB1 which exhibits no toxicity. To measure the toxin activity, we used a cell based assay that makes quantification more robust and is capable of detecting multiple samples simultaneously. It is an alternative to the qualitative duckling bioassay which is the "gold-standard" assay currently being used for quantitative analysis of active AFB1. AFB1 was incubated with transduced Vero cells expressing the green fluorescence protein (GFP) gene. After excitation with blue light at 475 nm, cells emitted green light with emission peak at 509 nm. The result shows that AFB1 inhibits protein expression in a concentration dependent manner resulting in proportionately less GFP fluorescence in cells exposed to AFB1. The result also indicates strong positive linear relationship with R(2)=0.90 between the low cost CCD camera and a fluorometer, which costs 100 times more than a CCD camera. This new analytical method for measuring active AFB1 is low in cost and combined with in vitro assay, is quantitative. It also does not require the use of animals and may be useful especially for laboratories in regions with limited resources. PMID- 26874108 TI - Detection EGFR exon 19 status of lung cancer patients by DNA electrochemical biosensor. AB - Epidermal growth factor receptor (EGFR) exon 19 mutation status is a very important prediction index for tyrosine kinase inhibitors (TKIs) therapy. In this paper, we constructed a superior selective sandwich-type electrochemical biosensor to detect in-frame deletions in exon 19 of EGFR in real samples of patients with non-small cell lung carcinoma. Based on the characteristics of different hybridization efficiency in different hybridization phase conditions, different region around EGFR exon 19 deletion hotspots was selected to design DNA probes to improve biosensor performance. The results confirm that alteration of deletion location in target deliberately according to different hybridization phase is able to improve selectivity of sandwich-type DNA biosensor. Satisfactory discrimination ability can be achieved when the deletions are located in the capture probe interaction region. In order to improve efficiency of ssDNA generation from dsDNA, we introduce Lambda exonuclease (lambda-exo) to sandwich type biosensor system. EGFR exon 19 statuses of clinical real samples from lung cancer patients can be discriminated successfully by the proposed method. Our research would make the electrochemical biosensor be an excellent candidate for EGFR detection for lung cancer patients. PMID- 26874109 TI - Aptamer selection by direct microfluidic recovery and surface plasmon resonance evaluation. AB - A surface plasmon resonance (SPR)-based SELEX approach has been used to raise RNA aptamers against a structured RNA, derived from XBP1 pre-mRNA, that folds as two contiguous hairpins. Thanks to the design of the internal microfluidic cartridge of the instrument, the selection was performed during the dissociation phase of the SPR analysis by recovering the aptamer candidates directly from the target immobilized onto the sensor chip surface. The evaluation of the pools was performed by SPR, simultaneously, during the association phase, each time the amplified and transcribed candidates were injected over the immobilized target. SPR coupled with SELEX from the first to the last round allowed identifying RNA aptamers that formed highly stable loop-loop complexes (KD equal to 8nM) with the hairpin located on the 5' side of the target. High throughput sequencing of two key rounds confirmed the evolution observed by SPR and also revealed the selection of hairpins displaying a loop not fully complementary to the loop of its target. These candidates were selected mainly because they bound 79 times faster to the target than those having a complementary loop. SELEX coupled with SPR is expected to speed up the selection process because selection and evaluation are performed simultaneously. PMID- 26874110 TI - Design and development of PCR-free highly sensitive electrochemical assay for detection of telomerase activity using Nano-based (liposomal) signal amplification platform. AB - Telomerase, which has been detected in almost all kinds of cancer tissues, is considered as an important tumor marker for early cancer diagnostics. In the present study, an electrochemical method based on liposomal signal amplification platform is proposed for simple, PCR-free, and highly sensitive detection of human telomerase activity, extracted from A549 cells. In this strategy, telomerase reaction products, which immobilized on streptavidin-coated microplate, hybridized with biotinylated capture probes. Then, dopamine-loaded biotinylated liposomes are attached through streptavidin to biotinylated capture probes. Finally, liposomes are ruptured by methanol and the released-dopamine is subsequently measured using differential pulse voltammetry technique by multi walled carbon nanotubes modified glassy carbon electrode. Using this strategy, the telomerase activity extracted from 10 cultured cancer cells could be detected. Therefore, this approach affords high sensitivity for telomerase activity detection and it can be regarded as an alternative to telomeric repeat amplification protocol assay, having the advantages of simplicity and less assay time. PMID- 26874111 TI - Molecularly imprinted plasmonic nanosensor for selective SERS detection of protein biomarkers. AB - Molecularly imprinted plasmonic nanosensor has been prepared via the rational design of an ultrathin polymer layer on the surface of gold nanorods imprinted with the target protein. This nanosensor enabled selective fishing-out of the target protein biomarker even from a complex real sample such as human serum. Sensitive SERS detection of the protein biomarkers with a strong Raman enhancement was achieved by formation of protein imprinted gold nanorods aggregates, stacking of protein imprinted gold nanorods onto a glass plate, or self-assembly of protein imprinted gold nanorods into close-packed array. High specificity and sensitivity of this method were demonstrated with a detection limit of at least 10(-8)mol/L for the target protein. This could provide a promising alternative for the currently used immunoassays and fluorescence detection, and offer an ultrasensitive, non-destructive, and label-free technique for clinical diagnosis applications. PMID- 26874115 TI - ESBRA Nordmann Award 2016. PMID- 26874112 TI - Ultrasensitive electrochemical immunoassay for surface array protein, a Bacillus anthracis biomarker using Au-Pd nanocrystals loaded on boron-nitride nanosheets as catalytic labels. AB - Bacillus anthracis, the causative agent of anthrax, is a well known bioterrorism agent. The determination of surface array protein (Sap), a unique biomarker for B. anthracis can offer an opportunity for specific detection of B. anthracis in culture broth. In this study, we designed a new catalytic bionanolabel and fabricated a novel electrochemical immunosensor for ultrasensitive detection of B. anthracis Sap antigen. Bimetallic gold-palladium nanoparticles were in-situ grown on poly (diallyldimethylammonium chloride) functionalized boron nitride nanosheets (Au-Pd NPs@BNNSs) and conjugated with the mouse anti-B. anthracis Sap antibodies (Ab2); named Au-Pd NPs@BNNSs/Ab2. The resulting Au-Pd NPs@BNNSs/Ab2 bionanolabel demonstrated high catalytic activity towards reduction of 4 nitrophenol. The sensitivity of the electrochemical immunosensor along with redox cycling of 4-aminophenol to 4-quinoneimine was improved to a great extent. Under optimal conditions, the proposed immunosensor exhibited a wide working range from 5 pg/mL to 100 ng/mL with a minimum detection limit of 1 pg/mL B. anthracis Sap antigen. The practical applicability of the immunosensor was demonstrated by specific detection of Sap secreted by the B. anthracis in culture broth just after 1h of growth. These labels open a new direction for the ultrasensitive detection of different biological warfare agents and their markers in different matrices. PMID- 26874117 TI - Nanomicelles based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake. AB - This study sought to develop a new type nanomicelle based on boronate ester linked poly(ethylene glycol)-b-poly(benzyl glutamate) (PEG-BC-PBLG) diblock copolymer as the carrier of doxorubicin (Dox) to achieve acid-induced detachment of PEG shells and subsequent boronic acid-mediated enhanced endocytosis. In vitro studies revealed that the PEG-BC-PBLG copolymer was stable in neutral solutions but tend to hydrolysed under acidic conditions, which was attributed to the acid sensitive properties of boronate ester bonds. The formation of PEG-BC@PBLG micelles was confirmed based on critical micelle concentration (CMC), particle size, and morphology observations. It was observed that these micelles were spherical with an average particle size of approximately 80nm, as measured by dynamic laser scattering (DLS), suggesting their passive targeting to tumour tissue and endocytosis potential. Dox-loaded PEG-BC@PBLG micelles (PEG BC@PBLG.Dox) showed sustained drug release profiles over 9h, and their cumulative drug release was dependent on the pH value of the environment. Remarkably, cellular uptake ability of PEG-BC@PBLG micelles was found to be higher than that of non-boronate ester-linked PEG@PBLG micelles due to boronic acid-mediated endocytosis, as revealed by confocal laser scanning microscopy (CLSM) imaging of fluorescein isothiocyanate (FITC) green-conjugated micelles, thereby providing higher cytotoxicity against HepG2 cells. The antitumour activity and toxicity of PEG-BC@PBLG.Dox micelles in vivo were evaluated in BLAB/c mice against HepG2 cell derived tumours. Compared with Dox, PEG-BC@PBLG.Dox showed reduced toxicity, whereas its tumour growth inhibition rate was 17% higher than that of free Dox. These results indicate the great potential of PEG-BC@PBLG micelles as the carrier of various lipophilic anticancer drugs with improved anti-tumour efficacy. PMID- 26874116 TI - Analysis of chromosome translocation frequency after a single CT scan in adults. AB - We recently reported an increase in dicentric chromosome (DIC) formation after a single computed tomography (CT) scan (5.78-60.27 mSv: mean 24.24 mSv) and we recommended analysis of 2000 metaphase cells stained with Giemsa and centromere FISH for dicentric chromosome assay (DCA) in cases of low-dose radiation exposure. In the present study, we analyzed the frequency of chromosome translocations using stored Carnoy's-fixed lymphocyte specimens from the previous study; these specimens were from 12 patients who were subject to chromosome painting of Chromosomes 1, 2 and 4. Chromosomes 1, 2 and 4 were analyzed in ~5000 cells, which is equivalent to the whole-genome analysis of almost 2000 cells. The frequency of chromosome translocation was higher than the number of DICs formed, both before and after CT scanning. The frequency of chromosome translocations tended to be higher, but not significantly higher, in patients with a treatment history compared with patients without such a history. However, in contrast to the results for DIC formation, the frequency of translocations detected before and after the CT scan did not differ significantly. Therefore, analysis of chromosome translocation may not be a suitable assay for detecting chromosome aberrations in cases of low-dose radiation exposure from a CT scan. A significant increase in the frequency of chromosome translocations was not likely to be detected due to the high baseline before the CT scan; the high and variable frequency of translocations was probably due to multiple confounding factors in adults. PMID- 26874118 TI - Mussel-inspired functionalization of PEO/PCL composite coating on a biodegradable AZ31 magnesium alloy. AB - The rapid degradation of magnesium-based implants in physiological environments in vivo not only will quickly deteriorate their mechanical strengths but will also lead to a severe change of the micro-environment around the implants, which may cause the final failure of magnesium-based implants. In this work, a polycaprolactone (PCL) layer was prepared to seal the plasma electrolytic oxidization coating (PEO) to form a PEO/PCL composite coating on a biodegradable AZ31 magnesium alloy, followed by further surface functionalization with polydopamine. The in vitro degradation behaviors of the bare AZ31 alloy and coated samples were evaluated in a simulated body fluid (SBF) using the potentiodynamic polarization curve test and the static immersion test. The bioactivity of the samples was investigated using the SBF soaking test. The cytocompatibility of all samples was evaluated using the cytotoxicity test and analysis of the adhesion and proliferation of osteoblast cells (MC3T3-E1) directly cultivated on the sample surface. The results showed that the PCL layer successfully sealed the pores of the PEO coating, and then the polydopamine layer formed on its surface. The in vitro degradation tests showed that the PEO/PCL composite coating improved the corrosion resistance of the AZ31 alloy in SBF with a more positive corrosion potential and a lower corrosion current density. Due to the protection of the PEO/PCL composite coating, the surrounding environment showed nearly no influence on the degradation of the coated sample, which led to no obvious local alkalization and hydrogen evolution. Moreover, compared with the AZ31 alloy and PEO coating, the PEO/PCL composite coating was more suitable for cell adhesion and proliferation. After further surface functionalization by polydopamine, the corrosion resistance of the composite coating was maintained, while its bioactivity was significantly enhanced with a large amount of hydroxyapatite (HA) formed on its surface after immersion in SBF. The initial cell adhesion and spread were also improved by the polydopamine. By further immobilizing polyhexamethylene biguanidine (PHMB) onto the coating surface via the assistance of polydopamine, good antibacterial ability was obtained. This feasible method for fabricating a cytocompatible and antibacterial composite coating on a biodegradable AZ31 alloy may be promising in implant applications due to the osteointegration and anti-infection properties of these materials post operation. PMID- 26874120 TI - Hepatocellular Carcinoma Masquerading as Gall Bladder Mass. PMID- 26874119 TI - Aqueous two-phase system cold-set gelation using natural and recombinant probiotic lactic acid bacteria as a gelling agent. AB - The present study aimed to entrap probiotic lactic acid bacteria (LAB) in a sodium alginate and sodium caseinate aqueous two-phase gel system. The natural acidifying properties of two therapeutic probiotic LAB were exploited to liberate calcium ions progressively from calcium carbonate (CaCO3), which caused the gelation of the co-existing phases. Bi-biopolymeric matrix gelation of GDL/CaCO3 or LAB/CaCO3 was monitored by dynamic rheological measurements, and the final gels were characterized by frequency dependence measurements and confocal laser scanning microscopy. Weak to strong gels were formed with an elastic modulus G' from 10 to 1.000Pa, respectively. After cold-set gelation of our system, confocal laser scanning microscopy showed spherical protein microdomains trapped within a calcium alginate network. LAB cells were stained to study their partition in the self-gelling matrices. Our LAB strains showed two different behaviors, which may relate to the exopolysaccharide production: (i) Lactobacillus plantarum CNRZ1997 cells were found mainly in continuous alginate networks, whereas (ii) Lactococcus lactis cells were localized in protein microdomains. This alginate-caseinate phase-separated system that was self-gelled by LAB cells may be an innovative approach for immobilizing and protecting LAB cells. PMID- 26874121 TI - Pulmonary Synovial Sarcoma of Unknown Origin. PMID- 26874122 TI - Hidradenoma Papilliferum: A Case Report of an Uncommon Perianal Lesion. PMID- 26874123 TI - Appendicitis--Current Practices in a Tertiary Referral Center. PMID- 26874124 TI - Sleeve Gastrectomy: Exposure of the Left Pillar. PMID- 26874125 TI - An Uncommon Presentation of Gastric Outlet Obstruction: Bouveret's Syndrome. PMID- 26874126 TI - Sigmoidocutaneous Fistula 26 Years after Left Inguinal Hernia Repair with Mesh Plug Technique. PMID- 26874127 TI - Hemorrhagic Shock from Spontaneous Splenic Rupture Requiring Open Splenectomy in a Patient Taking Rivaroxaban. PMID- 26874128 TI - Crawford Long, Alfred Blalock, Louis Wright, and Georgia's Surgical Heritage. AB - Georgia and the Atlanta area are associated with three important figures in the history of surgery. Crawford Long (1815-1878) discovered the anesthetic effects of ether while in practice in Jefferson. Born in Culloden, Alfred Blalock (1899 1964) was a pioneer researcher in shock and resuscitation, and developed the Blalock-Taussig shunt for Tetralogy of Fallot. His technician, African-American Vivien Thomas (1910-1985), was a full partner in the landmark advances. Louis T. Wright (1891-1952) was born in LaGrange and grew up in the Jim Crow South. As the country's leading black surgeon, he led the integration of major hospitals and helped lay the groundwork for the landmark civil rights legislation of the 1960s that integrated American medicine. Their stories, with roots in small towns in Georgia, reveal the deep surgical traditions of the South. PMID- 26874129 TI - Factors Associated with Return to Work Postinjury: Can the Modified Rankin Scale Be Used to Predict Return to Work? AB - The ability to return to work (RTW) postinjury is one of the primary goals of rehabilitation. The modified Rankin Scale (mRS) is a validated simple scale used to assess the functional status of stroke patients during rehabilitation. We sought to determine the applicability of mRS in predicting RTW postinjury in a general trauma population. The trauma registry was queried for patients, aged 18 to 65 years, discharged from 2012 to 2013. A telephone interview for each patient included questions about employment status and physical ability to determine the mRS. Patients who had RTW postinjury were compared with those who had not (nRTW). Two hundred and thirty-four patients met the inclusion criteria. Of these, 171 (72.5%) patients RTW and 63 (26.7%) did nRTW. Patients who did nRTW were significantly older, had longer length of stay and higher rates of in-hospital complications. Multivariate analysis revealed that older patients were less likely to RTW (odds ratio = 0.961, P = 0.011) and patients with a modified Rankin score <=2 were 15 times more likely to RTW (odds ratio = 14.932, P < 0.001). In conclusion, an mRS <=2 was independently associated with a high likelihood of returning to work postinjury. This is the first study that shows applicability of the mRS for predicting RTW postinjury in a trauma population. PMID- 26874130 TI - Acute Colonic Pseudo-obstruction: Defining the Epidemiology, Treatment, and Adverse Outcomes of Ogilvie's Syndrome. AB - Acute colonic pseudo-obstruction (ACPO) is a rare but often fatal disease. Herein, we present the largest study to date on ACPO. The National Inpatient Sample was queried for ACPO diagnoses from 1998 to 2011. Patients were analyzed by treatment into four groups: medical management (MM), colonoscopy alone [(endoscopy-only group) ENDO], surgery alone (SURG), or surgery and colonoscopy (SAC). Logistic regression was used to identify predictors of adverse outcomes by treatment group. There were 106,784 cases of ACPO: 96,657 (90.5%) MM, 2,915 (2.7%) ENDO, 6,731 (6.3%) SURG, and 481 (0.5%) SAC. The medical complication (45.7%), procedural complication (15.9%), and mortality rates (7.7%) were high. Increasing procedure invasiveness was independently associated with higher odds of medical complications, procedural complications, and death (P < 0.0125). The odds of death were significantly higher in the ENDO [odds ratio (OR) = 1.2], SURG (OR 1.4), and SAC (OR = 1.8) groups (P < 0.0125). Those who fail MM and require procedures have increasing morbidity and mortality with increasing invasiveness, likely reflecting the severity of their conditions. PMID- 26874131 TI - Inguinal Hernia Repair Using Self-adhering Sutureless Mesh: AdhesixTM: A 3-Year Follow-up with Low Chronic Pain and Recurrence Rate. AB - To review our experience and outcomes after inguinal hernia repair using the lightweight self-adhering sutureless mesh "AdhesixTM" and demonstrate the safety and efficacy of this mesh. This is a 3-year retrospective study that included 143 consecutive patients who underwent 149 inguinal hernia repairs at our department of surgery. All hernias were repaired using a modified Lichtenstein technique. Preoperative, perioperative, and postoperative data were prospectively collected. Incidence of chronic pain, postoperative complications, recurrence, and patient satisfaction were assessed three years postoperatively by conducting a telephone survey. We had 143 patients with a mean age of 58 years (17-84), who underwent 149 hernia repairs using the AdhesixTM mesh. Ninety-two per cent (131 patients) were males. Only 10 patients (7%) had a postoperative pain for more than three years. In our series, neither age nor gender was predictive of postoperative pain. Only one patient had a hematoma lasting for more than one month and only four patients (2.8%) had a recurrence of their hernia within three years of their initial surgery. Ninety per cent of the patient expressed their satisfaction when surveyed three years after their surgery. In conclusion, the use of the self adhering sutureless mesh for inguinal hernia repair has been proving itself as effective as the traditional mesh. AdhesixTM is associated with low chronic pain rate, recurrence rate, and postoperative complications rate, and can be safely adopted as the sole technique for inguinal hernia repair. PMID- 26874132 TI - Pseudoangiomatous Stromal Hyperplasia on Core Needle Biopsy Does Not Require Surgical Excision. AB - Pseudoangiomatous stromal hyperplasia (PASH) is an uncommon, benign localized fibrotic lesion. Historically, PASH has been difficult to differentiate from angiosarcoma. This difficulty has led to recommendations of surgical excision. We sought to identify the incidence of upgraded pathology to atypia or malignancy on surgical excisional biopsy after identification of PASH on core needle biopsy (CNB). A 5-year retrospective review at a single institution was conducted including all cases of PASH confirmed on CNB. The data set was divided into patients who underwent excisional biopsy and those followed only by imaging. Primary end points included the incidence of subsequent malignancy or high-risk pathology on histologic analysis or the presentation of suspicious imaging. Thirty-seven patients were reviewed, 19 (51.4%) underwent surgical excision and 18 (48.6%) were followed with imaging alone. A palpable mass was noted in 36.8 per cent of patients in the excisional group versus 5.6 per cent in the imaging group (P = 0.02). The median follow-up for the excisional and imaging groups were 43 and 35 months, respectively (P = 0.85). The 95 per cent confidence interval for the presence of malignancy was 0 to 9.4 per cent. Although further characterization of PASH is needed, our data support using CNB with follow-up imaging as a safe alternative to excisional biopsy in the absence of symptoms or other clinical factors. However, further research in this area is needed. PMID- 26874133 TI - Multiple Preoperative Endoscopic Retrograde Cholangiopancreatography and Large Common Bile Duct Diameter Predict the Need for Complex Surgery. AB - Endoscopic retrograde cholangiopancreatography (ERCP) is frequently used to clear the common bile duct (CBD) in patients with choledocholithiasis. While a single ERCP is usually effective, many patients undergo multiple ERCP attempts before cholecystectomy. Here we sought to identify preoperative factors predictive of surgical complexity beyond routine laparoscopic cholecystectomy after ERCP. Data were prospectively collected for all ERCPs between September 2010 and February 2012 at a public academic medical center including demographics, indication, stone presence, CBD diameter, sphincterotomy, stent placement, and ERCP number. A total of 124 ERCPs were attempted in 73 patients with choledocholithiasis, 10 per cent of whom presented with cholangitis. Fifty-six per cent of patients underwent one ERCP, whereas 16 per cent required >= 3 procedures. Laparoscopic cholecystectomy was performed in 58 (79%) patients whereas 15 (21%) patients required more complex operations including eight open CBD explorations and two hepaticojejunostomies. The likelihood of requiring more complex surgery correlated with increasing number of ERCPs with an adjusted odds ratio of 5.75 (95% confidence interval: 2.31-14.3, P <= 0.001). Increased CBD diameter also correlated with complex surgery with adjusted odds ratio of 1.5 (95% confidence interval: 1.10-2.06, P = 0.012) for each millimeter. The number of preoperative ERCPs and CBD diameter in choledocholithiasis patients are strong predictors of the need for open surgery and CBD exploration and should be considered in surgical planning and consent for patients requiring more than one ERCP procedure. PMID- 26874134 TI - Surgical Management of Retroperitoneal Soft Tissue Sarcomas: Role of Curative Resection. AB - Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. However, factors affecting the recurrence and long-term survival are not well understood. The aim of this study was to assess clinical, pathological, and treatment-related factors affecting prognosis in patients with retroperitoneal sarcomas. The hospital records of 107 patients who underwent surgical exploration at our unit for primary or recurrent retroperitoneal sarcomas between 1984 and 2013 were reviewed. Of these patients, 92 had a primary tumor and 15 had a recurrent neoplasm. Study end points included factors affecting overall and recurrence-free survival for the 92 patients with primary disease. Mean follow-up was 79.7 +/- 56.3 months. Only the patients undergoing surgery for primary sarcoma were included in this study. Overall 5-year survival was 71 per cent. Disease-free 5-year survival was 65 per cent. Only tumor grade affects overall and disease-free survival. This study confirmed the importance of an aggressive surgical management for retroperitoneal sarcomas to offer these patients the best chance of cure. In our series, only the tumor grade seems to be associated with worse outcome and higher rate of recurrence, regardless of the size of the tumor. PMID- 26874135 TI - Seat Belt Use and its Effect on Abdominal Trauma: A National Trauma Databank Study. AB - We sought to use the National Trauma Databank to determine the demographics, injury distribution, associated abdominal injuries, and outcomes of those patients who are restrained versus unrestrained. All victims of motor vehicle collisions (MVCs) were identified from the National Trauma Databank and stratified into subpopulations depending on the use of seat belts. A total of 150,161 MVC victims were included in this study, 72,394 (48%) were belted. Young, male passengers were the least likely to be wearing a seat belt. Restrained victims were less likely to have severe injury as measured by Injury Severity Score and Abbreviated Injury Score. Restrained victims were also less likely to suffer solid organ injuries (9.7% vs 12%, P < 0.001), but more likely to have hollow viscous injuries (1.9% vs 1.3%, P < 0.001). The hospital and intensive care unit length of stay were significantly shorter in belted victims with adjusted mean difference: -1.36 (-1.45, -1.27) and -0.96 (-1.02, -0.90), respectively. Seat belt use was associated with a significantly lower crude mortality than unrestrained victims (1.9% vs 3.3%, P < 0.001), and after adjusting for differences in age, gender, position in vehicle, and deployment of air bags, the protective effect remained (adjusted odds ratio for mortality 0.50, 95% confidence interval 0.47, 0.54). In conclusion, MVC victims wearing seat belts have a significant reduction in the severity of injuries in all body areas, lower mortality, a shorter hospital stay, and decreased length of stay in the intensive care unit. The nature of abdominal injuries, however, was significantly different, with a higher incidence of hollow viscous injury in those wearing seat belts. PMID- 26874136 TI - Impact of a Transfusion-free Program on Patients Undergoing Pancreaticoduodenectomy. AB - Patients undergoing pancreaticoduodenectomy (PD) often require transfusion. However, transfusion-related complications and decreased blood donation in Korea encourage the development of new treatment strategies for PD patients. Although transfusion-free (TF) operation is thought to be beneficial, results supporting its beneficial effects are lacking. The aim of our study was to demonstrate the impact on PD patients of a TF program. From December 2003 to April 2013, 80 consecutive patients with periampullary lesions underwent PD performed. These patients were divided into two groups as follows: 39 PD patients in the "before TF program" (Group 1) and 41 PD patients in the "after TF program" (Group 2). Among patients in Group 2, patients who agreed with the TF program were enrolled and proceed with the TF program prospectively. Participants in the TF program had perioperative blood augmentation and intraoperative acute normovolemic hemodilution. The perioperative data were compared with the two groups. The mean preoperative hemoglobin, operative times, and operative blood loss showed no significance between two groups. The mean postoperative hemoglobin was lower in Group 2 (11.7 g/dL vs 10.9 g/dL, P = 0.038). The mean amount of blood transfusion was significantly lower in Group 2. (950.8 mL vs 124.9 mL, P = 0.009). The TF program considerably decreases the amount of perioperative blood transfusion. The overall perioperative course and complication rate in the TF group were not inferior to those in the non-TF group. The TF program appears safe and should be considered in PD patients. PMID- 26874137 TI - Use of Payer as a Proxy for Health Insurance Status on Admission Results in Misclassification of Insurance Status among Pediatric Trauma Patients. AB - The purpose of this study was to quantify health insurance misclassification among children treated at a pediatric trauma center and to determine factors associated with misclassification. Demographic, medical, and financial information were collected for patients at our institution between 2008 and 2010. Two health insurance variables were created: true (insurance on hospital admission) and payer (source of payment). Multivariable logistic regression was used to determine which factors were independently associated with health insurance misclassification. The two values of health insurance status were abstracted from the hospital financial database, the trauma registry, and the patient medical record. Among 3630 patients, 123 (3.4%) had incorrect health insurance designation. Misclassification was highest in patients who died: 13.9 per cent among all deaths and 30.8 per cent among emergency department deaths. The adjusted odds of misclassification were 6.7 (95% confidence interval: 1.7, 26.6) among patients who died and 16.1 (95% confidence interval: 3.2, 80.77) among patients who died in the emergency department. Using payer as a proxy for health insurance results in misclassification. Approaches are needed to accurately ascertain true health insurance status when studying the impact of insurance on treatment outcomes. PMID- 26874138 TI - Outcomes of Recurrent Rectal Cancer after Transanal Excision. AB - Successful surgical salvage after transanal excision (TAE) of rectal cancers has historically been considered feasible, but results vary. We examine our experience in surgical salvage of locally recurrent rectal cancers after TAE. A retrospective review of patients undergoing salvage surgery for locally recurrent early-stage rectal cancer after TAE from March 1990 to March 2008 at our institution is presented here. Seventy-eight patients underwent TAE for tumor invades submucosa (T1) rectal cancer. Average age of patients was 68.3 years. Recurrence occurred in 17 patients (21.8%). Median number of months between the first operation and the recurrence was 41 months. Sixteen out of 17 patients recurred locally whereas one had only distant recurrence. Fourteen were eligible for surgical salvage. Ten patients underwent abdominoperineal resection, whereas four underwent repeat local excision. Eleven deaths were noted and the median survival after the first operation was 70.3 months. Disease-free survival after salvage surgery was 53 per cent (9/17), with a median follow-up of 68 months from the original surgery. Disease-specific mortality was 47 per cent (8/17), with a median survival of 72 months from the original surgery. Five-year survival in the recurrence group was 11/16 (69%). In conclusion, TAE for T1 rectal cancer carries a higher risk of recurrence. Of the local recurrences, 87.5 per cent underwent microscopic negative margins (R0) resection at the time of salvage and had a five year survival of 69 per cent. Long-term surveillance is encouraged, as recurrence can be seen even after 10 years from initial treatment. TAE can be considered for T1 rectal tumor with reasonable outcomes. PMID- 26874139 TI - An Assessment of Margins after Lumpectomy in Breast Cancer Management. AB - We performed this study to evaluate our indications for margin re-excision (MRE) in the management of cancer patients opting for breast conservation therapy (BCT). We identified patients choosing breast conservation therapy from January 2012 to May 2014. Margins were considered negative if >2 mm, close if <2 mm, and positive if ink was detected abutting tumor. Patients with close and positive margins underwent MRE. We identified 247 patients of which 190 had negative margins and did not require MRE, 46 patients had a close margin, and 11 had a positive margin, leading to an MRE rate of 23 per cent (57 of 247). The following variables were evaluated: tumor size, stage, estrogen receptor, progesterone receptor, HER2/neu receptor, and node status. None predicted the presence of tumor in the MRE specimen (P > 0.05). Patients with close margins had a 6.5 per cent (3 of 46), and patients with positive margins had a 36.4 per cent (4 of 11) incidence of tumor in the MRE specimens; this difference was statistically significant (P = 0.02). The low rate of finding tumor in MRE specimens of patients with close margins after lumpectomy for breast carcinoma argues for limiting MRE to patients with positive margins (ink on tumor) only. We have adopted this approach in our institution. PMID- 26874140 TI - Right Internal Jugular Vein Cannulation: Carotid Artery-directed versus Sternocleidomastoid-directed Methods. AB - The aim of the present study was to explore a simple and safe method for central venous catheterization (CVC) from the right internal jugular vein (RIJV) by comparing carotid artery (CA) positioning with sternocleidomastoid (SCM) positioning. The medical records of patients who underwent CVC between January 2011 and January 2015 were retrospectively reviewed. Central venous catheters were inserted into the RIJV either above the level of the cricoid cartilage using the CA-directed method (419 patients, Group 1) or below the level of the cricoid cartilage using the SCM-directed method (436 patients, Group 2). Success rate and related complications of catheterization were evaluated in the two groups. The total success rate of RIJV cannulation in Group 1 (97.2%) was higher than that in Group 2 (94.5%). Moreover, the success rate at first attempt was significantly higher in Group 1 than in Group 2 (92.4% vs 86.9%). The incidence of hematoma was 1.6 per cent in Group 1 and 3.8 per cent in Group 2. The rate of other complications such as pneumothorax, catheter-related infections, and catheter occlusion did not significantly differ between the groups. In conclusions, CA directed RIJV cannulation is more effective and simple to perform than the SCM directed method, and should become the preferred CVC technique in the absence of ultrasound guidance. PMID- 26874141 TI - Reduced Survival in Bariatric Surgery Candidates Delayed or Denied by Lack of Insurance Approval. AB - Bariatric surgery reduces mortality for Americans who meet candidacy criteria and have insurance coverage. Unfortunately, some medically suitable candidates are denied or delayed during insurance approval processes. The long-term impact of such care delays on survival is unknown. Using a prospectively maintained bariatric intake database, we identified consecutive applicants who were evaluated and medically cleared by our multidisciplinary care team and for whom insurance approval was requested. We compared survival in those who were initially approved by their insurance carriers (controls) and those who were initially denied coverage (subjects). Mortality was determined using the Social Security Death Index. Kaplan-Meier survival curves were plotted and the log-rank test for significance was applied. From August 2003 to December 2008, 463 patients (391 females, mean age 45 +/- 10 years, mean body mass index 52.5 +/- 9.4 kg/m(2)) were medically cleared for a bariatric procedure. Of these, 363 were approved by insurance on initial request, whereas 100 were denied. Given the study's intention to measure the aggregate impact of delays and denials, nine patients who later came to operation after appeal or coverage change were maintained in the subject cohort. During 0- to 113-month follow-up, six subjects (6%) died compared with seven controls (1.9%), corresponding to a statistically significant survival benefit for patients initially approved for bariatric surgery without delay or denial (P < 0.001). In conclusion, access to bariatric surgical care was impeded by insurance certification processes in 22 per cent of medically acceptable candidates. Processes that delay or restrict efficient access to bariatric surgery are associated with a 3-fold mortality increase. PMID- 26874142 TI - Inter-rater Variability Interferes with Reproducibility of Splenic Injury Grades Reported to the American College of Surgeons Committee on Trauma. AB - The objective of this study was to determine reproducibility of our splenic injury grading data, previously reported to the American College of Surgeons Committee on Trauma for our most recent site visit. The institutional registry of a Level I trauma center was queried to identify adult patients presenting with blunt splenic injury between January 1, 2013 and December 31, 2013. Original CT scans were scanned into the picture archiving and communication system and subsequently reviewed by four trauma surgeons and two radiologists for clinical impressions of splenic injury grade. Grades assigned by the clinician and the grade recorded in the registry were compared for inter-rater reliability using the intraclass correlation coefficient, as a means of assessing variance of ordinal data. The intraclass correlation coefficient in our model was 0.77, which indicates that 77 per cent of the observed variance was due to true variance and 23 per cent of the variance was due to error. Variability in grading may, in some cases, underestimate injury severity and compromise the clinician's expectation of clinical outcome, both in real-time, as well as during retrospective review processes such as those used during the trauma center reverification process. PMID- 26874143 TI - Thromboelastography Does Not Detect Preinjury Antiplatelet Therapy in Acute Trauma Patients. AB - Thromboelastography (TEG) with platelet mapping has been proposed as an assay to detect the presence of antiplatelet agents (APA), yet no study has evaluated TEG markers of platelet dysfunction in acute trauma patients stratified by the use of preinjury APA. We hypothesized that patients on preinjury APA would demonstrate prolonged TEG markers of platelet dysfunction compared with those not on preinjury APA. This retrospective review evaluated all trauma patients admitted to a Level I trauma center from February 2011 to April 2013 who received a TEG within the first 24 hours of admission. Patients were classified as receiving preinjury APA or no APA if their documented medications included either aspirin or adenosine diphosphate (ADP) antagonists, including clopidogrel, prasugrel, and ticagrelor. A total of 129 patients were included (APA, n = 35; no APA n = 94) in the study. The time from admission to the first TEG was similar (APA 175 +/- 289 minutes versus no APA 216 +/- 321 minutes, P = 0.5). There was no significant difference in TEG markers of platelet dysfunction, including per cent ADP inhibition (APA 61.7 +/- 25.8% versus no APA 62.3 +/- 28.8%; P = 0.91) or per cent arachidonic acid inhibition (APA 58.2 +/- 31% versus no APA 53.8 +/- 34%; P = 0.54). Both groups had similar proportion of severe platelet dysfunction, defined as ADP inhibition greater than 70 per cent (APA 40% versus no APA 40%; P = 0.8) and arachidonic acid inhibition greater than 70 per cent (APA 40% versus no APA 39%; P = 0.89). In conclusion, platelet dysfunction after major trauma is common. Therefore, TEG alone should not be used to evaluate for the presence of APA due to apparent lack of specificity. PMID- 26874144 TI - Colorectal Cancer Disparities at an Urban Tertiary Care Center. PMID- 26874145 TI - Does Isolated Hemoperitoneum Cause Peritonitis? A Review of 400 Trauma Laparotomies. PMID- 26874147 TI - Pediatric Unintentional Firearm injuries: A Northwestern Louisiana Trauma Center Analysis. PMID- 26874146 TI - Postoperative Ultrasound Evaluation of Gastric Distention: A Pilot Study. PMID- 26874148 TI - Management of severe asymmetric pectus excavatum complicating aortic repair in a patient with Marfan's syndrome. AB - We describe the case of a 28-year old man with Marfan's syndrome and severe pectus excavatum who required an aortic root replacement for an ascending aortic aneurysm. There was a near-vertical angulation of the sternum that presented challenges with opening and exposure of the heart during aortic surgery. Furthermore, removal of the sternal retractor after aortic repair resulted in sudden loss of cardiac output. A Ravitch procedure was then performed to successfully close the chest without further cardiovascular compromise. We propose that patients with a severe pectus excavatum and mediastinal displacement seen on preoperative CT scanning should be considered for simultaneous, elective repair. PMID- 26874149 TI - Editorial: 50 Years of the CJO: Looking back/looking forward. PMID- 26874151 TI - Prevalence of visual hallucinations in a national low vision client population. AB - PURPOSE: To evaluate the prevalence of visual hallucinations (Charles Bonnet syndrome) in a national population undergoing vision rehabilitation. STUDY DESIGN: Cross-sectional survey. PARTICIPANTS: Participants were 2565 new clients older than 40 years attending a Canadian National Institute for the Blind (CNIB) vision rehabilitation clinic. METHODS: Participants were asked the following question: "Many people who come to CNIB tell us that they see things they know are not there. Some see patterns or shapes. Others see images of people or animals. Have you ever experienced this?" Responses were cross-tabulated on the basis of age, sex, eye disease, visual acuity, and whether the clients lived alone. Multivariable logistic regression was used to analyze the responses. RESULTS: Overall, 18.8% of people surveyed indicated that they had experienced hallucinations. In the multivariable model, females showed higher odds of hallucinations than males did (odds ratio [OR] 1.32, 95% CI 1.06-1.64, p = 0.02). Clients with greater vision loss had higher chances of experiencing hallucinations than those with the lowest level of vision loss (OR 1.49, 95% CI 1.19-1.88, p = 0.0005). There was no significant difference in the chances of experiencing hallucinations between people with age-related macular degeneration, diabetic retinopathy, and glaucoma, or in older versus younger respondents. People who did not live alone had higher chances of experiencing hallucinations than those who lived alone (OR 1.54, 95% CI 1.19-1.98, p = 0.0009). CONCLUSIONS: Visual hallucinations are experienced by approximately 1 in 5 patients with vision loss caused by any eye disease, warranting greater awareness of the phenomenon among all vision health professionals and their patients. PMID- 26874152 TI - Wait times and volume of cataract surgery in Ontario: 2000-2012. AB - OBJECTIVE: To review cataract surgery trends and wait times in Ontario. DESIGN: Retrospective analysis of health records. METHODS: Ontario Health Insurance Plan billing service claims between 2000 and 2012 were analyzed for the yearly number of cataract surgeries, alone and in combination with other procedures. The number of Ontarians with cataracts was estimated by applying composite prevalence curves derived from published population data. This was then used to calculate the yearly number of procedures per 1000 Ontarians with cataracts. RESULTS: Per 1000 people with cataract, the rate of cataract extraction increased 18.9% overall from 2000 to 2012, increasing by 38.3% from 2000 to 2006 and decreasing by 14.6% from 2006 to 2012. Mean wait times for cataract surgery decreased by 45.8% from 2006 to 2009 and increased 28.5% from 2009 to 2013. The proportion of surgeries that were same-day bilateral cataract extraction increased 2.21-fold from 2000 to 2012 but represented only 0.82% of total cataract surgeries in 2012. In 2000, 3% of cataract surgeries were combined with other procedures, and this decreased to 1.8% in 2012. Of these combinations, the rates of combined glaucoma filtration procedures decreased by 44.3%, anterior vitrectomy decreased by 32.5%, posterior vitrectomy increased by 58.3%, and corneal transplantation decreased by 10.7% during this time period. CONCLUSIONS: The yearly rate of cataract surgery has decreased since 2006, and wait times have increased from 2009. Same-day bilateral cataract extraction represented less than 1% of the total cataract surgical volume. Rates of cataract combined with posterior vitrectomy have increased (58%), whereas anterior vitrectomy at the time of cataract surgery decreased (33%). PMID- 26874153 TI - Thermal evaluation of two phacoemulsification systems. AB - OBJECTIVE: To compare thermal profiles of new transversal ultrasound power modulation to torsional ultrasound in an artificial chamber and cadaver eye. DESIGN: Laboratory investigation. METHODS: John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, was the study setting. Temperature increase after 30 seconds was measured at the needle midshaft in an artificial chamber and at maximal friction point in a cadaver eye. Ellips FX (transverse) was tested at 100% power, as was Signature with micropulse settings (6 milliseconds on and off). OZil (torsional only) was tested at 100% power in the artificial chamber and cadaver eye. Runs were completed with aspiration blocked. Temperature was continuously measured on the phacoemulsification sleeve using a microthermistor probe connected to the BAT-10 multipurpose thermometer, with an accuracy of +/-0.1 degrees C. RESULTS: Transversal FX had a greater temperature increase than micropulse (p < 0.001) and torsional (p < 0.001). Micropulse had a greater temperature increase than torsional (p < 0.001). The cadaver eye had a greater temperature increase than the artificial chamber for torsional (p < 0.001). CONCLUSIONS: Higher heat accumulation and potential for incisional burn occurred with the cadaver model than with the artificial chamber, suggesting the need for caution when using 100% torsional ultrasound with aspiration blocked. Transversal FX generated more heat than was reported originally. Further study is needed to determine the incidence of incisional burn with varied power settings for this new model. Micropulse generated more heat than previous reports, but the increased efficiency is likely to negate potentially increased incisional burn risk. PMID- 26874154 TI - Comparison of intraocular pressure post penetrating keratoplasty vs Descemet's stripping endothelial keratoplasty. AB - OBJECTIVE: To compare the effect of Descemet's stripping endothelial keratoplasty (DSEK) with penetrating keratoplasty (PKP) on intraocular pressure (IOP) and use of ocular antihypertensives. DESIGN: Retrospective cohort study. PARTICIPANTS: Thirty-five eyes in 33 patients undergoing PKP and 43 eyes in 38 patients undergoing DSEK were included in the analysis. Fifteen eyes undergoing PKP and 12 undergoing DSEK had diagnosed glaucoma. Patients undergoing corneal transplant because of trauma, keratoconus, pellucid marginal degeneration, or prior failed transplant were excluded. METHODS: Charts were obtained for all patients who underwent PKP or DSEK by a single surgeon at the Ivey Eye Institute between 2003 and 2010. IOP and all IOP-lowering medications were recorded preoperatively and at 1, 4, 8, 12, and 24 weeks postoperatively. Complications, graft survival, and glaucoma surgeries were noted. RESULTS: There was no significant difference in preoperative IOP between the 2 groups (p = 0.30). Postoperatively, IOP was significantly higher in the PKP group at 1 week (p < 0.01), 4 weeks (p < 0.01), and 8 and 12 weeks (p < 0.05), but not at 24 weeks (p = 0.62). Mean IOP increased significantly post-transplant in all groups (p < 0.05). In patients without glaucoma, postoperative IOP elevation requiring treatment occurred in 68% of PKP eyes and 23% of DSEK eyes. In patients with prior glaucoma, an increased requirement for ocular antihypertensives occurred in 60% of PKP eyes and 20% of DSEK eyes. Three trabeculectomies and 1 tube shunt were performed in the cohort with glaucoma undergoing PKP. No glaucoma surgery was required in the DSEK cohort. CONCLUSIONS: Elevation of IOP requiring treatment occurred at a lower rate after DSEK compared with PKP. This difference was significant during the early postoperative course but nonsignificant at 24 weeks. Additional long-term studies on the effect of DSEK on glaucoma and IOP control are warranted. PMID- 26874155 TI - Assessing accuracy of non-eye care professionals as trainee vision screeners for children. AB - OBJECTIVE: To determine the level of agreement between non-eye care trainees and a trainer (ophthalmologist) in a vision screening program. DESIGN: Prospective, observational study carried out in 3 phases (Phase I-III). PARTICIPANTS: Study population included 1228 children, aged 6-14 years, at 5 elementary schools in the city of Hamilton. METHODS: In Phase I, 1228 children were screened by the trainee screeners, of which 273 children failed the vision testing. Of these 273 children, 170 consented to enrolment into Phase II and were examined by an ophthalmologist, who confirmed that 105 of these children were true positives. On retesting (Phase III), the ophthalmologist passed 158 of the 163 randomly selected children who passed in Phase I. RESULTS: Overall, trainee screeners had a sample sensitivity of 95.5% and sample specificity of 70.8% in detecting children who should fail vision screening. When we used the positive and negative prediction values obtained, 198 of the 1228 children had vision impairment providing an estimated prevalence of 16.1%, or 161 children per 1000 population. CONCLUSIONS: Non-eye care professionals can be trained to an acceptable degree of accuracy to perform certain vision screening tests on children. Such screening methods may be a useful approach to address existing gaps in provision of eye care for many Canadian children, thereby ensuring that all children receive timely vision screening. PMID- 26874156 TI - Relationship between cantho-limbal distance and degree of head turn in a Korean population. AB - OBJECTIVE: To evaluate the relationship between cantho-limbal distance and the degree of head turn in Koreans. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Thirty patients without strabismus or nystagmus who had visited an ophthalmic clinic at a single medical center were included in the study. METHODS: The distance between the lateral canthus and lateral corneal limbus was measured using a 5 mm scale. The degree of head turn was measured with a goniometer when the cantho-limbal distances were 0, 5, and 10 mm. The degree of head turn was measured 3 times, and the mean value was used as the degree of head turn. RESULTS: When the cantho-limbal distances were 0, 5, and 10 mm, the degree of head turn values were 42.33, 30.47, and 2.53 degrees, respectively. The shorter the cantho-limbal distance, the higher the degree of head turn (r = -0.945, p < 0.01). The relationship was expressed as: Degree of head turn = -2.98 * cantho limbal distance + 35.07. CONCLUSIONS: Cantho-limbal distance can be used to estimate the degree of head turn. This method may be simpler and easier in a clinical situation than checking the degree of head turn with a goniometer. PMID- 26874157 TI - Comparison of treatment for congenital nasolacrimal duct obstruction: a systematic review and meta-analysis. AB - OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials comparing the success and complication rates among various congenital nasolacrimal duct obstruction (CNLDO) procedures, intervention times, and tubes types. DESIGN: Systematic review with quantitative meta-analysis. METHODS: Studies were identified by searching the PubMed, EMBASE, SCOPUS, and Cochrane databases. The comparisons between categorical variables were analyzed using the chi(2) test, and the dichotomous outcomes were reported as risk ratios. The precision of the effect size was based on the 95% confidence interval. RESULTS: Seven studies published between 2007 and 2013 were included. Immediate versus observation/deferred probing had similar rates of success (82.7% vs 81.8%). Balloon dacryocystoplasty and silicone intubation had similar rates of success (79.8% vs 77.8%). Monocanalicular and bicanalicular intubation had similar rates of success (88.3% vs 88.0%). The dislocation rates for monocanalicular versus bicanalicular intubation were 8.5% and 9.8%, respectively. CONCLUSIONS: Immediate and deferred probing do not differ in their success rates. No difference in success rates was observed between balloon dilation and intubation. Monocanalicular and bicanalicular intubation were similar in their success and dislocation rates. Therefore, the preference of surgeons on the treatment of CNLDO should be discussed with parents to ensure the best possible outcome. PMID- 26874158 TI - Epiretinal membrane in diabetes mellitus patients screened by nonmydriatic fundus camera. AB - OBJECTIVE: To determine the prevalence of epiretinal membrane (ERM) in patients with type 2 diabetes mellitus (T2DM) and to assess the associated risk factors. DESIGN: Retrospective, cross sectional study. METHODS: Patients with T2DM, seen for annual follow-up between 2009 and 2010, were evaluated by digital nonmydriatic retinal photography for the detection of diabetic retinopathy. Retinal photographs were assessed by a retina specialist. RESULTS: ERM was present in 102 of 1550 patients with T2DM (6.5%). Of the participants, 1443 had sufficient documented data to conduct statistical analysis for variant risk factors. The prevalence of ERM was significantly associated with age (p < 0.001; 1.2% for <49 years, 4% for 50-59 years, 8.2% for 60-69 years, and 9.6% for >70 years), cataract surgery (p < 0.001), diabetic nephropathy (p < 0.001), and chronic renal failure (p = 0.039). Prevalence was similar for both sexes (53% females, 47% males; p = 0.33). In logistic regression models, the prevalence of ERM was significantly associated with increasing age (p = 0.018), cataract surgery (p < 0.001), and diabetic nephropathy (p = 0.011). CONCLUSIONS: The prevalence of ERM in patients with T2DM in the present study was not significantly different than that of the general population. ERM was significantly associated with age, diabetic nephropathy, and cataract surgery. PMID- 26874159 TI - Topical difluprednate monotherapy for uveitic macular edema. AB - OBJECTIVE: To describe the use of topical difluprednate for the treatment of uveitic macular edema. DESIGN: Retrospective review of 3 consecutive cases of uveitic macular edema. METHODS: Patients were treated with topical difluprednate monotherapy. RESULTS: All patients experienced complete resolution of uveitic macular edema within 2-4 weeks. We observed a statistically significant improvement in central subfield macular thickness (p = 0.04). There was an overall improvement in visual acuity, but this result was not statistically significant (p = 0.33). CONCLUSIONS: Topical difluprednate can be effective for uveitic macular edema. Further investigation of this therapy in prospective randomized controlled trials is warranted. PMID- 26874160 TI - Comment on: Peripapillary RNFL thickness in nonexudative versus chronically treated exudative age-related macular degeneration. PMID- 26874161 TI - Assessment of online health resources for ophthalmology patients with age-related macular degeneration or diabetic retinopathy. PMID- 26874162 TI - Combined hamartoma of the retina and RPE: A spectrum of presentation with epiretinal membrane masquerade. PMID- 26874163 TI - Case report: Choroidal abscess after double lung transplantation in a cystic fibrosis patient. PMID- 26874164 TI - Visual function alterations in Alzheimer Disease: A case report. PMID- 26874165 TI - Focal cross-linking: description of a novel technique for localizing collagen cross-linking. PMID- 26874166 TI - Bilateral Rhizopus keratitis in a cocaine user. PMID- 26874168 TI - Spontaneous resolution of optic disc pit maculopathy after posterior vitreous detachment. PMID- 26874167 TI - Bilateral conjunctival Splendore-Hoeppli phenomenon associated with juvenile xanthogranuloma. PMID- 26874169 TI - Masquerade macular exudation in Mallatia Leventinese. PMID- 26874170 TI - Orbital dermoid presenting as a case of ptosis with monocular elevation deficiency. PMID- 26874171 TI - Eye love you. PMID- 26874172 TI - Radioactive seed implantation in treatment of an eyelid primary Merkel cell carcinoma. PMID- 26874173 TI - Intraorbital arteriovenous fistula of the ophthalmic vein-embolization using the thombosed superior ophthalmic vein approach. PMID- 26874174 TI - Posterior subcapsular cataracts and hypotony secondary to severe pembrolizumab induced uveitis: Case report. PMID- 26874175 TI - Coronary arteritis: An entity to be considered in giant cell arteritis. PMID- 26874176 TI - A case of POEMS and chronic papilledema with preserved optic nerve function. PMID- 26874177 TI - Endovascular Closure of Chronic Dissection Entries in the Aortic Arch Using the Amplatzer Vascular Plug II as a Sealing Button. AB - PURPOSE: To present a new endovascular technique to avoid open surgical arch reconstruction in selected patients with aneurysmal dilatation due to small chronic dissection entries in the aortic arch. TECHNIQUE: The true and the false lumen of the aortic arch are catheterized from the femoral arteries. An Amplatzer Vascular Plug II (AVP II) is advanced through the proximal entry from the false lumen side and deployed as a sealing button in the entry hole, with 1 disc in the true lumen and the remaining 2 discs in the false lumen. This technique was used in 4 patients with chronic dissection involving the aortic arch, three of whom had had previous surgery for acute type A aortic dissection. In 3 patients, the false lumen of the thoracic aorta was successfully obliterated, with thrombosis and aortic diameter reduction during follow-up. In 1 patient, false lumen flow persisted, and he was subsequently treated with a total arch reconstruction and frozen elephant trunk. CONCLUSION: Endovascular closure of small proximal dissection entries in the aortic arch with an AVP II used as a sealing button is feasible and may be an alternative to open surgical arch reconstruction in selected patients with chronic aortic dissection and secondary aneurysm expansion. PMID- 26874178 TI - Preservation of Clinically Relevant Accessory Renal Arteries in Infrarenal AAA Patients With Adequate Proximal Landing Zones Undergoing EVAR. AB - PURPOSE: To report techniques to preserve the flow to relevant accessory renal arteries (ARA) in patients undergoing infrarenal endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) with adequate landing zones. METHODS: ARAs that originate inferior to the lowest ipsilateral main renal artery, supply one-third of the renal parenchyma, and having a diameter >4 mm have significant clinical importance. Between May 2012 and January 2015, among 389 high-risk patients with infrarenal AAAs who underwent standard EVAR, 9 (2.3%) patients each presented with a coexistent clinically relevant ARA. Their perfusion was secured by placing covered stents in the target ARA, parallel and outside of the main abdominal, as chimney grafts. Evaluation of acute and chronic renal decline was based on the consensus definition of RIFLE criteria (risk, injury, failure, loss, and end-stage) and chronic kidney disease (CKD) staging system, respectively. RESULTS: The procedure was completed successfully in all cases. In the immediate postoperative period, no acute kidney injury was observed based on the RIFLE criteria. Eight of the 9 covered stents remained patent during a mean follow-up of 13.8 +/- 6.2 months. A single covered stent occlusion was observed 30 days postoperatively with infarction of the caudal pole of the kidney. This patient developed renal function impairment based on the CKD staging system 12 months after the initial procedure. For the remaining 8 patients, improvement of one CKD stage (n=1) or no change (n=7) in the CKD stage was observed. CONCLUSION: In AAA patients unfit for surgical revascularization, EVAR is associated with a significant decline in renal function. For this reason, preservation of relevant coexistent ARAs using the chimney technique should be considered as an option. PMID- 26874179 TI - Impact of Perioperative Complications After Endovascular Therapy in Diabetic Patients With Critical Limb Ischemia due to Isolated Infrapopliteal Lesions. AB - PURPOSE: To investigate the thus far poorly defined impact of perioperative complications (POCs) on clinical outcomes after endovascular therapy (EVT) of diabetic patients with critical limb ischemia (CLI) due to isolated infrapopliteal lesions. METHODS: A multicenter registry of CLI patients was interrogated to identify 780 consecutive diabetic patients (mean age 71 +/- 10 years; 553 men) who successfully underwent balloon angioplasty for isolated infrapopliteal lesions. More than half of the population (487 patients) was on dialysis. Independent predictors (logistic regression) and prognostic impact on outcomes (Cox proportional hazards model) of POC (ie, death, myocardial infarction, stroke, pseudoaneurysm, puncture site hemorrhage/hematoma, distal emboli, vascular rupture, transfusion, dialysis, and gastrointestinal hemorrhage) were investigated. Outcomes are presented as the odds ratio (OR) and hazard ratio (HR), respectively, with 95% confidence intervals (CI). RESULTS: POCs occurred in 12.3% (96/780) of the population. Multivariate modeling identified body mass index (BMI) <18.5 kg/m(2) (adjusted OR 1.71, 95% CI 1.01 to 2.89, p=0.047) and tissue loss (adjusted OR 2.43, 95% CI 1.14 to 5.15, p=0.021) as independent predictors of POCs. In a Cox regression model adjusted for baseline clinical characteristics, the occurrence of POCs was independently associated with major adverse limb events (HR 1.87, 95% CI 1.12 to 3.13, p=0.016) but not with mortality or wound healing. In follow-up, freedom from major adverse limb events was higher in the group without POC (85.2%) than with POC (69.7%, p=0.006) at up to 3 years. CONCLUSION: POCs within 30 days after balloon angioplasty for infrapopliteal disease in diabetics with CLI were more likely to occur in patients with low BMI and tissue loss. POC occurrence was associated with major adverse limb events in follow-up but not with mortality or wound healing. PMID- 26874180 TI - Transcutaneous carbon dioxide monitoring for the prevention of neonatal morbidity and mortality. AB - BACKGROUND: Carbon dioxide (CO2) measurement is a fundamental evaluation in a neonatal intensive care unit (NICU), as both low and high values of CO2 might have detrimental effects on neonatal morbidity and mortality. Though measurement of CO2 in the arterial blood gas is the most accurate way to assess the amount of CO2, it requires blood sampling and it does not provide a continuous monitoring of CO2. OBJECTIVES: To assess whether the use of continuous transcutaneous CO2 (tcCO2) monitoring in newborn infants reduces mortality and improves short and long term respiratory and neurodevelopmental outcomes. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 11), MEDLINE via PubMed (1966 to November 1, 2015), EMBASE (1980 to November 1, 2015), and CINAHL (1982 to November 1, 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. SELECTION CRITERIA: Randomized, quasi-randomized and cluster randomized controlled trials comparing different strategies regarding tcCO2 monitoring in newborns. Three comparisons were considered, that is, continuous tcCO2 monitoring versus 1) any intermittent modalities to measure CO2; 2) other continuous CO2 monitoring; and 3) with or without intermittent CO2 monitoring. DATA COLLECTION AND ANALYSIS: We used the standard methods of the Cochrane Neonatal Review Group. Two review authors independently assessed studies identified by the search strategy for inclusion. MAIN RESULTS: Our search strategy yielded 106 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion, nor ongoing trials. AUTHORS' CONCLUSIONS: There was no evidence to recommend or refute the use of transcutaneous CO2 monitoring in neonates. Well-designed, adequately powered randomized controlled studies are necessary to address efficacy and safety of transcutaneous CO2 monitoring in neonates. PMID- 26874181 TI - Parahippocampal Cortex Processes the Nonspatial Context of an Event. AB - Parahippocampal cortex (PHc) is known to process spatial information, both in perceptual and episodic memory studies. However, recent theories propose an expanded role for PHc in processing context information in general, whether spatial or nonspatial. The current study used a source memory paradigm to investigate encoding and retrieval of nonspatial context information. Human participants were asked to judge lexical aspects of word stimuli and to retrieve those judgments during a later memory test. Anterior PHc showed significantly greater activation for items associated with correct source judgments than items associated with incorrect source judgments during both encoding and retrieval phases. These findings suggest that the role of PHc in episodic memory cannot be limited to spatial information. PMID- 26874182 TI - Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention. AB - Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks. PMID- 26874183 TI - Direct Visualization and Mapping of the Spatial Course of Fiber Tracts at Microscopic Resolution in the Human Hippocampus. AB - While hippocampal connectivity is essential to normal memory function, our knowledge of human hippocampal circuitry is largely inferred from animal studies. Using polarized light microscopy at 1.3 um resolution, we have directly visualized the 3D course of key medial temporal pathways in 3 ex vivo human hemispheres and 2 ex vivo vervet monkey hemispheres. The multiple components of the perforant path system were clearly identified: Superficial sheets of fibers emanating from the entorhinal cortex project to the presubiculum and parasubiculum, intermixed transverse and longitudinal angular bundle fibers perforate the subiculum and then project to the cornu ammonis (CA) fields and dentate molecular layer, and a significant alvear component runs from the angular bundle to the CA fields. From the hilus, mossy fibers localize to regions of high kainate receptor density, and the endfolial pathway, mostly investigated in humans, merges with the Schaffer collaterals. This work defines human hippocampal pathways underlying mnemonic function at an unprecedented resolution. PMID- 26874184 TI - Structural and Maturational Covariance in Early Childhood Brain Development. AB - Brain structural covariance networks (SCNs) composed of regions with correlated variation are altered in neuropsychiatric disease and change with age. Little is known about the development of SCNs in early childhood, a period of rapid cortical growth. We investigated the development of structural and maturational covariance networks, including default, dorsal attention, primary visual and sensorimotor networks in a longitudinal population of 118 children after birth to 2 years old and compared them with intrinsic functional connectivity networks. We found that structural covariance of all networks exhibit strong correlations mostly limited to their seed regions. By Age 2, default and dorsal attention structural networks are much less distributed compared with their functional maps. The maturational covariance maps, however, revealed significant couplings in rates of change between distributed regions, which partially recapitulate their functional networks. The structural and maturational covariance of the primary visual and sensorimotor networks shows similar patterns to the corresponding functional networks. Results indicate that functional networks are in place prior to structural networks, that correlated structural patterns in adult may arise in part from coordinated cortical maturation, and that regional co-activation in functional networks may guide and refine the maturation of SCNs over childhood development. PMID- 26874186 TI - Elder Abuse Severity: A Critical but Understudied Dimension of Victimization for Clinicians and Researchers. AB - Purpose of the Study: To describe the variation in severity of elder emotional abuse, physical abuse, and neglect and identify factors associated with more severe forms of elder mistreatment (EM). Design and Methods: Population-based study using random digit-dial sampling and telephone interviews with a representative sample (n = 4,156) of community-dwelling, cognitively intact older adults in New York State. The Conflict Tactics Scale and DUKE Older Americans Resources and Services scales were adapted to assess EM subtypes. For each EM subtype, severity was operationalized by summing the number of different mistreatment behaviors and the frequency of each behavior. Among older adults reporting some degree of mistreatment, ordinal or multinomial regression predicted severity of elder emotional abuse, physical abuse, and neglect. Results: Distribution of EM severity was characterized by a negative/right skew. More severe emotional abuse was predicted by younger age, living with the perpetrator only, Hispanic background, and higher education. Increasing physical abuse severity was associated with younger age and living only with the perpetrator. Higher neglect severity was associated with functional impairment, younger age, living only with the perpetrator, lower income, and lower education. The presence of nonperpetrator others living in the home served a protective function against escalating mistreatment severity. Implications: Extends existing EM risk factor research by operationalizing mistreatment phenomena along a continuum of severity. Findings enhance capacity to screen and report particularly vulnerable EM victims and inform targeted interventions to ameliorate the problem. Incorporation of severity into EM research/measurement reflects the clinical and phenomenological reality of the problem. PMID- 26874185 TI - Subtype-Specific Genes that Characterize Subpopulations of Callosal Projection Neurons in Mouse Identify Molecularly Homologous Populations in Macaque Cortex. AB - Callosal projection neurons (CPN) interconnect the neocortical hemispheres via the corpus callosum and are implicated in associative integration of multimodal information. CPN have undergone differential evolutionary elaboration, leading to increased diversity of cortical neurons-and more extensive and varied connections in neocortical gray and white matter-in primates compared with rodents. In mouse, distinct sets of genes are enriched in discrete subpopulations of CPN, indicating the molecular diversity of rodent CPN. Elements of rodent CPN functional and organizational diversity might thus be present in the further elaborated primate cortex. We address the hypothesis that genes controlling mouse CPN subtype diversity might reflect molecular patterns shared among mammals that arose prior to the divergence of rodents and primates. We find that, while early expression of the examined CPN-enriched genes, and postmigratory expression of these CPN enriched genes in deep layers are highly conserved (e.g., Ptn, Nnmt, Cited2, Dkk3), in contrast, the examined genes expressed by superficial layer CPN show more variable levels of conservation (e.g., EphA3, Chn2). These results suggest that there has been evolutionarily differential retraction and elaboration of superficial layer CPN subpopulations between mouse and macaque, with independent derivation of novel populations in primates. Together, these data inform future studies regarding CPN subpopulations that are unique to primates and rodents, and indicate putative evolutionary relationships. PMID- 26874187 TI - Perceptions of Sedentary Behavior Among Socially Engaged Older Adults. AB - Purpose: To better understand the perceptions of sedentary behavior, its pros and cons, and the barriers associated with reducing sedentary time as it pertains to older adults. Design and Methods: Four focus group sessions were conducted with older adults (n = 26). Each focus group lasted approximately 45min, was led by an experienced qualitative researcher, and utilized probing questions on the definition of sedentary behavior, pros and cons of sedentary behavior, and programming needs for sedentary time reduction. Sessions were recorded and transcribed verbatim. Two researchers independently extracted data from the transcripts and identified major themes and subthemes. Data on sociodemographics and current activity levels were collected via questionnaires. Results: Participants were 74+/-8.5 years old and were primarily women (77%). They self reported sitting for 5.6+/-1.7h per day and engaging in physical activity for 172+/-115min/day. Four themes were identified. The first theme indicated that older adults have varied definitions of the term sedentary behavior and that they have a negative perception of this term. The second theme indicated that participants perceived social, cognitive, and physical benefits to the sedentary activities in which they engaged, and that these activities were meaningful. The third theme indicated that physical health was the only perceived disadvantage of engaging in sedentary activities. Finally, the fourth theme indicated that there were several perceived barriers to sedentary time reduction, both person and environment related. Implications: These findings have implications for use of terminology in policy and public health strategies targeting sedentary time reduction in older adults. PMID- 26874189 TI - Attachment to Life: Psychometric Analyses of the Valuation of Life Scale and Differences Among Older Adults. AB - PURPOSE OF STUDY: Examine psychometric properties of Lawton's Valuation of Life (VOL) scale, a measure of an older adults' assessment of the perceived value of their lives; and whether ratings differ by race (White, Black/African American) and sex. DESIGN AND METHODS: The 13-item VOL scale was administered at baseline in 2 separate randomized trials (Advancing Better Living for Elders, ABLE; Get Busy Get Better, GBGB) for a total of 527 older adults. Principal component analyses were applied to a subset of ABLE data (subsample 1) and confirmatory factor analyses were conducted on remaining data (subsample 2 and GBGB). Once the factor structure was identified and confirmed, 2 subscales were created, corresponding to optimism and engagement. Convergent validity of total and subscale scores were examined using measures of depressive symptoms, social support, control-oriented strategies, mastery, and behavioral activation. For discriminant validity, indices of health status, physical function, financial strain, cognitive status, and number of falls were examined. RESULTS: Trial samples (ABLE vs. GBGB) differed by age, race, marital status, education, and employment. Principal component analysis on ABLE subsample 1 (n = 156) yielded two factors subsequently confirmed in confirmatory factor analyses on ABLE subsample 2 (n = 163) and GBGB sample (N = 208) separately. Adequate fit was found for the 2-factor model. Correlational analyses supported strong convergent and discriminant validity. Some statistically significant race and sex differences in subscale scores were found. IMPLICATIONS: VOL measures subjective appraisals of perceived value of life. Consisting of two interrelated subscales, it offers an efficient approach to ascertain personal attributions. PMID- 26874188 TI - Future-Oriented Thought Patterns Associated With Anxiety and Depression in Later Life: The Intriguing Prospects of Prospection. AB - Anxiety and mood disorders in later life are the focus of an increasing amount of intervention research, however basic mechanisms and paradigms explaining etiology and maintenance warrant further exploration. Research on future-oriented thought patterns associated with anxiety and depression in this age group may prove useful, as these disorders are both characterized by a tendency to generate and fixate on threat-related future scenarios that may or may not materialize. Additionally, depression is associated with a reduced expectancy of positive future events. In this paper, we review the literature relevant to future thinking in anxiety and depression in older adults. We focus on the mental construction and anticipation of negative future events, and their underlying neurocognitive mechanisms. We then consider clinical and research implications of anxious and depressive future-oriented thought patterns for older adults. We believe that more research investigating future-oriented thought patterns associated with emotional disorders in later life could improve conceptualization, measurement, and perhaps potential treatments for late-life anxiety and depression. PMID- 26874190 TI - Honoring the Everyday Preferences of Nursing Home Residents: Perceived Choice and Satisfaction With Care. AB - Purpose of the Study: The nursing home (NH) culture change movement advocates for residents to be able to make choices about important aspects of their care. This study seeks to understand NH residents' perceptions of choice that they have in the care they receive while in the NH setting. We examine the association between residents' perceived choice and satisfaction with care preferences being met using a mixed methods approach. Design and Methods: Using the Preferences of Everyday Living Inventory, cognitive interviews were completed with 39 NH residents which resulted in a total of 600 item-level ratings of residents' perceived choice and satisfaction and corresponding open-ended comments on choice. Results: Quantitative findings revealed a significant Pearson correlation between residents' perceived choice and satisfaction (r = .47, p < .001). Participants' responses of free choice were linked to significantly higher ratings of satisfaction compared to no choice and some choice. Responses of some choice were associated with significantly higher ratings of satisfaction than the no choice group. Open-ended comments provided greater depth in understanding regarding how residents perceive the level of choice in fulfilling their preferences. Implications: This study establishes a positive association between NH residents' perceived choice and feelings of satisfaction with their care preferences being met. Offering choices that are deemed favorable or solicited from NH residents is a fundamental step toward increasing resident satisfaction with NH care. PMID- 26874191 TI - Residential Reasoning and the Tug of the Fourth Age. AB - Purpose of the Study: Where to grow older occupies the minds of many aging adults. This study examines how anticipation of the fourth age influences third age residential reasoning. It also investigates the role of social relationships in choosing housing for later life. Design and Methods: Analyses were based on semi-structured interviews with 30 community-dwelling retirees aged 67-97 who were asked about preparations for the future, including housing. Results: Replies about future housing fell into two categories: preemptive and contingent. In preemptive reasoning, participants anticipated that their current homes would be suitable over the long term and explained why, while those engaged in contingent reasoning could imagine a possible future move to more supportive housing and even had destination places in mind. Both types of responses reflect residential reasoning that is ongoing and driven in large part by anticipation of fourth-age vulnerabilities. Peers influenced participants' thinking about whether, when, and where to move. Relationships with spouses and offspring were also factors commonly mentioned in residential reasoning, both in terms of sources of support and perceived obligations. Implications: The fourth age is generally conceived as an experience of loss, but it also functions as a social imaginary. Our study suggests that the fourth age, both as a potential personal destiny and a social construct, influences housing decisions among those firmly in the third age. More attention in housing research to prudential anticipation of the fourth age as well as the relational aspects of residential reasoning would enhance understanding of late-life housing choices. PMID- 26874192 TI - Central Airway Obstruction: Benign Strictures, Tracheobronchomalacia, and Malignancy-related Obstruction. AB - The purpose of this article is to provide an update on methods for palliating symptoms in patients with histologically benign and malignant central airway obstruction. We review the published literature within the past decade on postintubation, posttracheostomy, and TB- and transplant-related airway strictures; tracheobronchomalacia; and malignant airway obstruction. We review terminology, classification systems, and parameters that impact treatment decisions. The focus is on how airway stent insertion fits into the best algorithm of care. Several case series and cohort studies demonstrate that airway stents improve dyspnea, lung function, and quality of life in patients with airway obstruction. Airway stenting, however, is associated with high rates of adverse events and should be used only when curative open surgical interventions are not feasible or are contraindicated. PMID- 26874195 TI - Calebin A downregulates osteoclastogenesis through suppression of RANKL signalling. AB - Osteoporosis is a bone disease that is exacerbated by aging and age-associated chronic diseases such as cancer. Cancer-induced bone loss is usually treated with bisphosphonates or denosumab, an antibody against receptor activator of nuclear factor (NF)-kappaB ligand (RANKL). Because these drugs are expensive and have numerous side effects and high rates of toxicity, safer, more effective, and more affordable therapies for osteoporosis are still needed. We identified a compound, calebin A (CA), derived from turmeric (Curcuma longa) that affects osteoclastogenesis through modulation of the RANKL signalling pathway. The CA's effect on NF-kappaB activation was examined by electrophoretic mobility shift assay. Using mouse macrophages in vitro model, we found that CA suppressed RANKL induced osteoclast differentiation of macrophages into osteoclasts, and downregulate RANKL-induced osteoclastogenesis-related marker gene expression, including NFATc-1, TRAP, CTR, and cathepsin K. CA also suppressed the osteoclastogenesis induced by multiple myeloma and breast cancer cells. This effect of CA was correlated with suppression of the phosphorylation and degradation of inhibitor of kappaB and, thus, inhibition of NF-kappaB activation. Furthermore, we found that an NF-kappaB-specific inhibitory peptide blocked RANKL induced osteoclastogenesis, demonstrating that the NF-kappaB signalling pathway is mandatory for RANKL-induced osteoclastogenesis. Our results conclusively indicate that CA downmodulates the osteoclastogenesis induced by RANKL and by tumour cells through suppression of NF-kappaB pathway. PMID- 26874193 TI - Structural analysis of the TKB domain of ubiquitin ligase Cbl-b complexed with its small inhibitory peptide, Cblin. AB - Cbl-b is a RING-type ubiquitin ligase. Previously, we showed that Cbl-b-mediated ubiquitination and proteosomal degradation of IRS-1 contribute to muscle atrophy caused by unloading stress. The phospho-pentapeptide DGpYMP (Cblin) mimics Tyr612 phosphorylated IRS-1 and inhibits the Cbl-b-mediated ubiquitination and degradation of IRS-1 in vitro and in vivo. In this study, we confirmed the direct interaction between Cblin and the TKB domain of Cbl-b using NMR. Moreover, we showed that the shortened tripeptide GpYM also binds to the TKB domain. To elucidate the inhibitory mechanism of Cblin, we solved the crystal structure of the TKB-Cblin complex at a resolution of 2.5 A. The pY in Cblin inserts into a positively charged pocket in the TKB domain via hydrogen-bond networks and hydrophobic interactions. Within this complex, the Cblin structure closely resembles the TKB-bound form of another substrate-derived phosphopeptide, Zap-70 derived phosphopeptide. These peptides lack the conserved intrapeptidyl hydrogen bond between pY and a conserved residue involved in TKB-domain binding. Instead of the conserved interaction, these peptides specifically interact with the TKB domain. Based on this binding mode of Cblin to the TKB domain, we can design drugs against unloading-mediated muscle atrophy. PMID- 26874194 TI - Modeling IL-1 induced degradation of articular cartilage. AB - In this study, we develop a computational model to simulate the in vitro biochemical degradation of articular cartilage explants sourced from the femoropatellar grooves of bovine calves. Cartilage explants were incubated in culture medium with and without the inflammatory cytokine IL-1alpha. The spatio temporal evolution of the cartilage explant's extracellular matrix components is modelled. Key variables in the model include chondrocytes, aggrecan, collagen, aggrecanase, collagenase and IL-1alpha. The model is first calibrated for aggrecan homeostasis of cartilage in vivo, then for data on (explant) controls, and finally for data on the IL-1alpha driven proteolysis of aggrecan and collagen over a 4-week period. The model was found to fit the experimental data best when: (i) chondrocytes continue to synthesize aggrecan during the cytokine challenge, (ii) a one to two day delay is introduced between the addition of IL-1alpha to the culture medium and subsequent aggrecanolysis, (iii) collagen degradation does not commence until the total concentration of aggrecan (i.e. both intact and degraded aggrecan) at any specific location within the explant becomes <= 1.5 mg/ml and (iv) degraded aggrecan formed due to the IL-1alpha induced proteolysis of intact aggrecan protects the collagen network while collagen degrades in a two step process which, together, significantly modulate the collagen network degradation. Under simulated in vivo conditions, the model predicts increased aggrecan turnover rates in the presence of synovial IL-1alpha, consistent with experimental observations. Such models may help to infer the course of events in vivo following traumatic joint injury, and may also prove useful in quantitatively evaluating the efficiency of various therapeutic molecules that could be employed to avoid or modify the course of cartilage disease states. PMID- 26874196 TI - Slow-binding inhibition of cholinesterases, pharmacological and toxicological relevance. AB - Slow-binding inhibition (SBI) of enzymes is characterized by slow establishment of enzyme-inhibitor equilibrium. Cholinesterases (ChEs) display slow onset of inhibition with certain inhibitors. After a survey of SBI mechanisms, SBI of ChEs is examined. SBI results either from simple slow interaction, induced-fit, or slow conformational selection. In some cases, the slow equilibrium is followed by an irreversible chemical step. This later was observed for the interaction of ChEs with certain irreversible inhibitors. Because slow-binding inhibitors present pharmacological advantages over classical reversible inhibitors (e.g. long target-residence times, resulting in prolonged efficacy with minimal unwanted side effects), slow-binding inhibitors of ChEs are promising new drugs for treatment of Alzheimer disease, myasthenia, and neuroprotection. SBI is also of toxicological importance; it may play a role in mechanisms of resistance and protection against poisoning by irreversible agents. PMID- 26874197 TI - Biomonitoring of a polluted coastal area (Bay of Muggia, Northern Adriatic Sea): A five-year study using transplanted mussels. AB - The subcellular effects of pollution were evaluated using two lysosomal biomarkers in mussels, Mytilus galloprovincialis, deployed periodically over a period of 5 years in a harbour area in the Bay of Muggia (Gulf of Trieste, North Adriatic Sea) that is strongly influenced by anthropogenic activities. Mussels were collected from a clean marine farm and analysed (sample T0). A sub-sample was transplanted to the harbour site (sample M) and analysed after about 12 weeks. An additional sub-sample was relocated within the farm as a control and was also tested at the end of the 12-week period (sample T1). The transplantation procedures were repeated twice yearly for 5 consecutive years, starting in 2009. Two well-established lysosomal biomarkers, i.e. lysosomal membrane stability and lipofuscin accumulation, were evaluated in hepatopancreas cells. The body condition index and mortality rate were also assessed. Moreover, various pollutants were determined in both mussel flesh, for a better comprehension of the biological response, and sediments, for a general characterization of the study area. As a whole, the applied biomarkers were found to be appropriate for determining the responses of mussels to environmental pollutant loads over time. Variations in lysosomal membrane stability and lipofuscin content were mostly related to total PAHs and metals respectively. Our results confirm the usefulness of active biomonitoring in evaluating pollution trends in marine coastal areas and in particular the value of lysosomal biomarkers as a rapid screening tool for highlighting pollutant effects at least at organism level. PMID- 26874198 TI - A multiple regression normalization approach to evaluation of gait in total knee arthroplasty patients. AB - BACKGROUND: Gait features characteristic of a cohort may be difficult to evaluate due to differences in subjects' demographic factors and walking speed. The aim of this study was to employ a multiple regression normalization method that accounts for subject age, height, body mass, gender, and self-selected walking speed in the evaluation of gait in unilateral total knee arthroplasty patients. METHODS: Three-dimensional gait analysis was performed on 45 total knee arthroplasty patients and 31 aged-matched controls walking at their self-selected speed. Gait data peaks including joint angles, ground reaction forces, net joint moments, and net joint powers were normalized using subject body mass, standard dimensionless equations, and a multiple regression approach that modeled subject age, height, body mass, gender, and self-selected walking speed. FINDINGS: Normalizing gait data using subject body mass, dimensionless equations, and multiple regression approach resulted in a significantly lower knee adduction moment and knee extensor power in total knee arthroplasty patients compared to controls (p<0.05). In contrast to normalization using body mass and dimensionless equations, multiple regression normalization greatly reduced variance in gait data by minimizing correlations with subject demographic factors and walking speed, resulting in significantly higher peak hip extension angles and peak hip flexion powers in total knee arthroplasty patients (p<0.05). INTERPRETATION: Total knee arthroplasty patients generate greater hip extension angles and hip flexor power and have a lower knee adduction moment than healthy controls. This gait pattern may be a strategy to reduce muscle and joint loading at the knee. PMID- 26874199 TI - Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells. AB - OBJECTIVES: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. DESIGN AND METHODS: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. RESULTS: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean+/-SEM) of Sesn2 in patients with MPEs was 0.54+/-0.22ng/mL while in BPEs it was 0.12+/ 0.04ng/mL (p=0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p=0.89 and p=0.64 respectively). CONCLUSIONS: Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells. PMID- 26874200 TI - Mass spectrometric quantification of salivary metanephrines-A study in healthy subjects. AB - BACKGROUND: Determination of metanephrine (MN), normetanephrine (NMN), and 3 methoxytyramine (3-MT) in saliva may offer potential diagnostic advantages in diagnosing pheochromocytoma. METHODS: In this preliminary study, we determined metanephrine concentrations in saliva of healthy subjects and the relationship with simultaneously measured plasma metanephrines. We also studied the possible influence of pre-analytical conditions such as a collection device, awakening, posture, and eating on the salivary metanephrine levels. RESULTS: Eleven healthy subjects were included. Fasting blood and saliva samples were collected in seated position and after 30min of horizontal rest. Plasma and salivary MN, NMN, and 3 MT concentrations were determined using a high-performance liquid chromatography tandem mass spectrometric technique (LC-MS/MS) with automated solid phase extraction sample preparation. Metanephrines were detectable in saliva from all participants both in seated and supine position. No significant correlations were observed between the MN, NMN, and 3-MT concentrations in saliva and plasma in seated or supine position. Furthermore, there was no difference between MN, NMN, and 3-MT samples collected with or without a collection device. CONCLUSION: Metanephrines can be detected in saliva with LC-MS/MS with sufficient sensitivity and precision. Our findings warrant evaluation of salivary metanephrine measurement as a novel laboratory tool in the work-up of patients suspected of having a pheochromocytoma. PMID- 26874201 TI - Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane dependent multimerization. AB - Binding of coagulation factors X (fX) and Xa (fXa) to activated platelets is required for the formation of membrane-dependent enzymatic complexes of intrinsic tenase and prothrombinase. We carried out an in-depth characterization of fX/fXa binding to phospholipids and gel-filtered, thrombin-activated platelets. Flow cytometry, surface plasmon resonance, and computational modeling were used to investigate interactions of fX/fXa with the membranes. Confocal microscopy was employed to study fXa binding to platelet thrombi formed in flowing whole blood under arterial conditions. Binding of fX/fXa to either vesicles or procoagulant platelets did not follow a traditional one-step reversible binding model. Their dissociation was a two-step process resulting in a plateau that was up to 10-fold greater than the saturation value observed in the association experiments. Computational modeling and experimental evidence suggested that this was caused by a combination of two-step association (mainly for fX) and multimerization on the membrane (mainly for fXa). Importantly, fX formed multimers with fXa, thereby improving its retention. The same binding/dissociation hysteresis was observed for annexin V known to form trimers on the membranes. Experiments with platelets from gray syndrome patients showed that alpha-granular factor Va provided an additional high-affinity binding site for fXa that did not affect the hysteresis. Confocal microscopy observation of fXa binding to platelet thrombi in a flow chamber and its wash-out confirmed that this phenomenon persisted under physiologically relevant conditions. This suggests its possible role of "locking" coagulation factors on the membrane and preventing their inhibition in plasma and removal from thrombi by flow. PMID- 26874203 TI - Proteolytic cleavage in the S1-S2 linker of the Kv1.5 channel does not affect channel function. AB - Kv1.5 channels mediate the ultra-rapidly activating delayed rectifier potassium current (IKur), which is important for atrial repolarization. It has been shown that cell-surface Kv1.5 channels are sensitive to cleavage by the extracellular serine protease, proteinase K (PK). Here, we investigated the effects of extracellular proteolytic digestion on the function of Kv1.5 channels stably expressed in HEK 293 cells. Our data demonstrate that PK treatment cleaved mature membrane-bound (75kDa) Kv1.5 channels at a single locus in the S1-S2 linker, producing 42-kDa N-terminal fragments and 33-kDa C-terminal fragments. Interestingly, such PK treatment did not affect the Kv1.5 current (IKv1.5) recorded using the whole-cell patch clamp technique. Analysis of cell-surface proteins isolated using biotinylation indicated that the PK-generated N- and C terminal fragments were both present in the plasma membrane. Co immunoprecipitation (co-IP) experiments indicated that the N- and C-terminal fragments are no longer associated after cleavage. Furthermore, following PK digestion, the N- and C-fragments degraded at different rates. PK is frequently used as a tool to analyze cell-surface localization of membrane proteins, and cleavage of cell-surface channels has been shown to abolish channel function (e.g. hERG). Our data, for the first time, demonstrate that cleavage of cell surface channels assessed by Western blot analysis does not necessarily correlate with an elimination of the channel activities. PMID- 26874204 TI - Insights into the function of ion channels by computational electrophysiology simulations. AB - Ion channels are of universal importance for all cell types and play key roles in cellular physiology and pathology. Increased insight into their functional mechanisms is crucial to enable drug design on this important class of membrane proteins, and to enhance our understanding of some of the fundamental features of cells. This review presents the concepts behind the recently developed simulation protocol Computational Electrophysiology (CompEL), which facilitates the atomistic simulation of ion channels in action. In addition, the review provides guidelines for its application in conjunction with the molecular dynamics software package GROMACS. We first lay out the rationale for designing CompEL as a method that models the driving force for ion permeation through channels the way it is established in cells, i.e., by electrochemical ion gradients across the membrane. This is followed by an outline of its implementation and a description of key settings and parameters helpful to users wishing to set up and conduct such simulations. In recent years, key mechanistic and biophysical insights have been obtained by employing the CompEL protocol to address a wide range of questions on ion channels and permeation. We summarize these recent findings on membrane proteins, which span a spectrum from highly ion-selective, narrow channels to wide diffusion pores. Finally we discuss the future potential of CompEL in light of its limitations and strengths. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26874202 TI - Computational virology: From the inside out. AB - Viruses typically pack their genetic material within a protein capsid. Enveloped viruses also have an outer membrane made up of a lipid bilayer and membrane spanning glycoproteins. X-ray diffraction and cryoelectron microscopy provide high resolution static views of viral structure. Molecular dynamics (MD) simulations may be used to provide dynamic insights into the structures of viruses and their components. There have been a number of simulations of viral capsids and (in some cases) of the inner core of RNA or DNA packaged within them. These simulations have generally focussed on the structural integrity and stability of the capsid and/or on the influence of the nucleic acid core on capsid stability. More recently there have been a number of simulation studies of enveloped viruses, including HIV-1, influenza A, and dengue virus. These have addressed the dynamic behaviour of the capsid, the matrix, and/or of the outer envelope. Analysis of the dynamics of the lipid bilayer components of the envelopes of influenza A and of dengue virus reveals a degree of biophysical robustness, which may contribute to the stability of virus particles in different environments. Significant computational challenges need to be addressed to aid simulation of complex viruses and their membranes, including the need to integrate structural data from a range of sources to enable us to move towards simulations of intact virions. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26874205 TI - Fullerenol C60(OH)24 increases ion permeability of lipid membranes in a pH dependent manner. AB - Fullerenols are water-soluble analogs of fullerene exhibiting both antioxidant and prooxidant activities in vitro and in vivo. Here we report, for the first time, that fullerenol C60(OH)24 can induce ion permeability of a planar lipid bilayer membrane via the formation of ion pores or conductive defects with a preference for cations over anions. The fullerenol-mediated electrical current displayed non-linear concentration dependence and was reversibly enhanced by alkalinization. Calcium and magnesium ions decreased the fullerenol-induced potassium ion permeability. Voltage dependence of the current was sensitive to membrane composition, with the conductance being well pronounced in fully saturated diphytanoylphosphatidylcholine. Fullerenol did not induce carboxyfluorescein leakage from liposomes, suggesting a small size of fullerenol induced pores. In contrast to ion permeability, the binding of C60(OH)24 to liposomes increased at acidic pH, as measured by fluorescence quenching of pyrene labeled lipid. In line with this, the photodynamic action of fullerenol on the peptide gramicidin A also increased at low pH. It is hypothesized that aggregates of fullerenol may stabilize transient conductive lipid defects or pores formed under a variety of stress conditions. PMID- 26874206 TI - Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases. AB - The function of human nervous system is critically dependent on proper interneuronal communication. Exosomes and other extracellular vesicles are emerging as a novel form of information exchange within the nervous system. Intraluminal vesicles within multivesicular bodies (MVBs) can be transported in neural cells anterogradely or retrogradely in order to be released into the extracellular space as exosomes. RNA loading into exosomes can be either via an interaction between RNA and the raft-like region of the MVB limiting membrane, or via an interaction between an RNA-binding protein-RNA complex with this raft-like region. Outflow of exosomes from neural cells and inflow of exosomes into neural cells presumably take place on a continuous basis. Exosomes can play both neuro protective and neuro-toxic roles. In this review, we characterize the role of exosomes and microvesicles in normal nervous system function, and summarize evidence for defective signaling of these vesicles in disease pathogenesis of some neurodegenerative diseases. PMID- 26874207 TI - Effect of dimerization on the mechanism of action of aurein 1.2. AB - The mechanism of action of antimicrobial peptides depends on physicochemical properties such as structure, concentration, and oligomerization. Here, we focused on the effect of dimerization on the mechanism of action of aurein 1.2 (AU). We designed a lysine-linked AU dimer, (AU)2K, and its interaction with membrane mimetics was studied using four biophysical techniques and molecular dynamics simulations. Circular dichroism and molecular dynamics studies showed that AU displayed a typical spectrum for disordered structures in aqueous solution whereas (AU)2K exhibited the typical spectrum of alpha-helices in a coiled-coil conformation, wherein helices are wrapped around each other. With the addition of large unilamellar vesicles (LUVs), AU adopted an alpha-helix structure whereas the coiled-coil structure of (AU)2K assumed an extended conformation. Carboxyfluorescein release experiments with LUVs showed that both peptides were able to permeabilize vesicles although the leakage response to increases in peptide concentration differed. Optical microscopy experiments showed that both peptides induced pore opening and the dimer eventually caused the vesicles to burst. Finally, calorimetric traces determined by isothermal titration calorimetry on the LUVs also showed significant differences in peptide membrane interactions. Together, the results of our study demonstrated that dimerization changes the mechanism of action of AU. PMID- 26874208 TI - Cognitive autonomy among adolescents with and without hearing loss: Associations with perceived social support. AB - Cognitive autonomy is a skill which may help adolescents prepare for important decisions in adulthood. The current study examined the associations between cognitive autonomy and perceived social support among adolescents with and without hearing loss. Participants were 177 students: 55 were deaf and hard of hearing (dhh) and 122 were hearing. They completed the Cognitive Autonomy and Self-Evaluation Inventory, the Multidimensional Scale of Perceived Social Support, and a demographic questionnaire. Significant positive correlations were found between some of the cognitive autonomy variables and some of the perceived social support variables. However, among the dhh group, they were fewer and weaker. Family support was found to be a significant predictor of three out of the five cognitive autonomy variables. In addition, significant differences were found between the dhh and hearing participants in some of the cognitive autonomy variables, but not in perceived social support. Implications for theory and practice are discussed. PMID- 26874209 TI - A 3-year follow-up study on cardiovascular disease and mortality in older people with intellectual disabilities. AB - BACKGROUND: With increasing longevity and a similar or increased prevalence of cardiovascular disease risk factors (as compared to the general population), people with intellectual disabilities (IDs) are at risk of developing cardiovascular disease. However, prospective studies on incidence and influencing factors of cardiovascular disease and mortality are lacking. METHODS: A three year follow-up study was undertaken to study the incidence and symptoms at presentation of myocardial accident, stroke and heart failure in older people with ID. Furthermore, the predictive value of cardiovascular disease risk factors on myocardial accident, stroke and heart failure and on all-cause mortality were studied. The baseline group consisted of the 1050 participants, aged 50 years and over, in the Dutch Healthy Ageing and Intellectual Disability (HA-ID) study. Baseline measurements were conducted between November 2008 and July 2010. Three years after baseline, medical files of 790 participants were studied. RESULTS: Cardiovascular disease (myocardial infarction, stroke and heart failure) occurred in 5.9% of the population during 3 year follow-up, and 32% of them died due to the condition. Incidence of myocardial infarction is 2.8 per 1000 personyears, for stroke 3.2 per 1000 personyears and for heart failure 12.5 per 1000 personyears. Incidence of these conditions is probably underestimated, due to atypical symptom presentation. The use of atypical antipsychotics and a history of heart failure were predictive for myocardial infarction. Heart failure was predicted by abdominal obesity, chronic kidney disease and a history of heart failure. A total of cardiovascular disease (myocardial infarction, stroke or heart failure) was predicted by abdominal obesity, a history of stroke and a history of heart failure. A low body-mass index, peripheral arterial disease, chronic kidney disease and inflammation were predictive for 3-year all-cause mortality. CONCLUSION: Incidence of cardiovascular disease in older people with ID is similar to that in the general population. A pro-active assessment and treatment of the presented cardiovascular disease risk factors may reduce cardiovascular disease and mortality in older people with ID. PMID- 26874210 TI - EMF protects cardiomyocytes against hypoxia-induced injury via heat shock protein 70 activation. AB - Intracellular calcium (Ca(2+)i) overload induced by chronic hypoxia alters Ca(2+)i homeostasis, whereas ameliorating calcium homeostasis is believed to be responsible for cardioprotection. We hypothesize that cardioprotection by electromagnetic fields (EMF) exposure may restore Ca(2+)i homeostasis altered by hypoxia insults. Cardiomyocytes isolated from neonatal Sprague-Dawley rats were exposed to chronic hypoxia (1% O2, 5% CO2, 37 degrees C). We observed that cardiomyocytes injury and hypertrophy were alleviated in hypoxic cardiomyocytes exposed with EMF preconditioning. Compared with hypoxic cardiomyocytes, the diastolic [Ca(2+)]i was decreased, the amplitude of Ca(2+)i oscillations was recovered when cardiomyocytes exposed with EMF. In addition, we also found that EMF exposure significantly increased heat shock protein 70 (HSP70) mRNA expression in hypoxic cardiomyocytes. However, treatment with HSP70 blocker KNK437, almost completely inhibited the EMF induced-cardioprotection and the beneficial effects of Ca(2+) oscillation in hypoxic cardiomyocytes. These results suggest that EMF preconditioning ameliorates Ca(2+)i homeostasis through activating HSP70, thereby producing the cardioprotective effect and reduction in hypoxic cardiomyocytes damage. PMID- 26874211 TI - Theoretical calculations, DNA interaction, topoisomerase I and phosphatidylinositol-3-kinase studies of water soluble mixed-ligand nickel(II) complexes. AB - Eight water soluble mixed-ligand nickel(II) complexes of the type [NiL(1 4)(diimine)H2O].(ClO4)2, (1-8) where L(1-4) = 2-((2-(piperazin-1 yl)ethylimino)methyl)-4-substituted phenols, and diimine = 2,2'-bipyridyl (bpy) or 1,10-phenanthroline (phen) were synthesized and characterized by elemental analysis and spectroscopic methods. The uncoordinated perchlorate anions was ascertained form IR spectra of the complexes, and the absorption spectra reveal the octahedron geometry around nickel(II) ion with tridentate Schiff base ligand, diimine and a coordinated water molecule. Cyclic voltammograms of the complexes indicate the one-electron irreversible processes in the cathodic and anodic region. In vitro antioxidant activity proved the significant radical scavenging activity of the complexes against DPPH radical. The groove/electrostatic binding nature of complexes with CT-DNA (calf thymus deoxyribonucleic acid) were affirmed by absorption, hydrodynamic and voltammetric titration experiments and docking analysis. All the complexes exhibit significant cleavage activity on plasmid DNA via hydrolytic and oxidatively, in which the oxidative mechanism involves hydroxyl radicals and supports the possibility of minor-groove binding. The complex 4 shows significant topoisomerase I (Topo-I) inhibitory activity. The molecular modeling analysis of complexes with phosphatidylinositol-3-kinase (PI3K) receptor indicate the hydrogen bonding with Met1039, Asp837 and Leu1027, and hydrophobic interactions with Ser488, Asn498, Asp500, Gln662, Lys668, Ile844, Ile847, Ile850, Val941, Leu942, Leu1020, Met1034, Leu1035, Thr1037, Met1039, Gln1041 and Ile1051 of subdomain IIA of BSA. The complexes show sigma-pi interaction between diimines and amino groups of Leu1030 and Arg839. PMID- 26874212 TI - Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice. AB - Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL 1beta, TNF- alpha, IL-6 and TGF-beta1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-beta, alpha-SMA, p Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM. PMID- 26874214 TI - Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant. AB - OBJECTIVE: Symptomatic infections of the central nervous system (CNS) with JC polyomavirus (JCV) usually occur as a result of immunocompromise and manifest as progressive multifocal leukoencephalopathy (PML) or granule cell neuronopathy (GCN). After immune reconstitution, some of these cases may show long-term persistence of JCV and delayed clinical improvement despite inflammation. METHODS: We followed 4 patients with multiple sclerosis, who developed natalizumab-associated PML or GCN with regard to JC viral load and JCV-specific T cell responses in the CNS. All of them experienced immune reconstitution inflammatory syndrome (IRIS), but in 2 cases JCV persisted > 21 months after IRIS accompanied by delayed clinical improvement. RESULTS: Persistence of JCV was associated with a lack of JCV VP1-specific T-cell responses during immune reconstitution in 1 of the patients. Detailed analysis of the brain infiltrate in another patient with neuronal persistence of JCV revealed strong infiltration of CD8(+) T cells and clonal expansion of activated CD8(+) effector T cells with a CD4(dim) CD8(+) phenotype, both exhibiting exquisite specificity for conserved epitopes of JCV large T antigen. However, clearance of JCV was not efficient, because mutations in the major capsid protein VP1 caused reduced CD4(+) T-cell responses against the identified JCV variant and subsequently resulted in a decline of CD8(+) T-cell responses after IRIS. INTERPRETATION: Our findings suggest that efficient CD4(+) T-cell recognition of neurotropic JCV variants is crucial to support CD8(+) T cells in combating JCV infection of the CNS. PMID- 26874215 TI - In extremely preterm infants, do the Movement Assessment of Infants and the Alberta Infant Motor Scale predict 18-month outcomes using the Bayley-III? AB - BACKGROUND: Extremely preterm infants are at high-risk for neurodevelopmental disabilities. The Movement Assessment of Infants (MAI) and the Alberta Infant Motor Scale (AIMS) have been designed to predict outcome with modest accuracy with the Bayley-I or Bayley-II. AIMS: To examine and compare the predictive validity of the MAI and AIMS in determining neurodevelopmental outcome with the Bayley-III. DESIGN: Retrospective cohort study of 160 infants born at <= 28 weeks gestation. METHOD: At their corrected age, infants underwent the MAI at 4 months, the AIMS at 4 and 10-12 months, and the Bayley-III and neurological examination at 18 months. Sensitivity and specificity were calculated. RESULTS: Infants had a mean gestation of 26.3 +/- 1.4 weeks and birth weight of 906 +/- 207 g. A high risk score (>= 14) for adverse outcome was obtained by 57% of infants on the MAI. On the AIMS, a high-risk score (<5th percentile) was obtained by 56% at 4 months and 30% at 10-12 months. At 18 months, infants with low-risk scores on either the MAI or AIMS had higher cognitive, language, and motor Bayley-III scores than those with high-risk scores. They were less likely to have severe neurodevelopmental impairment. To predict Bayley-III scores <70, sensitivity and specificity were 91% and 49%, respectively, for the MAI and 78% and 48%, respectively, for the AIMS. CONCLUSIONS: Extremely preterm infants with low-risk MAI at 4 months or AIMS scores at 4 or 10-12 months had better outcomes than those with high-risk scores. However, both tests lack specificity to predict individual neurodevelopmental status at 18 months. PMID- 26874213 TI - Effects of dopamine D1-like and D2-like antagonists on cocaine discrimination in muscarinic receptor knockout mice. AB - Muscarinic and dopamine brain systems interact intimately, and muscarinic receptor ligands, like dopamine ligands, can modulate the reinforcing and discriminative stimulus (S(D)) effects of cocaine. To enlighten the dopamine/muscarinic interactions as they pertain to the S(D) effects of cocaine, we evaluated whether muscarinic M1, M2 or M4 receptors are necessary for dopamine D1 and/or D2 antagonist mediated modulation of the S(D) effects of cocaine. Knockout mice lacking M1, M2, or M4 receptors, as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline in a food-reinforced drug discrimination procedure. Effects of pretreatments with the dopamine D1 antagonist SCH 23390 and the dopamine D2 antagonist eticlopride were evaluated. In intact mice, both SCH 23390 and eticlopride attenuated the cocaine discriminative stimulus effect, as expected. SCH 23390 similarly attenuated the cocaine discriminative stimulus effect in M1 knockout mice, but not in mice lacking M2 or M4 receptors. The effects of eticlopride were comparable in each knockout strain. These findings demonstrate differences in the way that D1 and D2 antagonists modulate the S(D) effects of cocaine, D1 modulation being at least partially dependent upon activity at the inhibitory M2/M4 muscarinic subtypes, while D2 modulation appeared independent of these systems. PMID- 26874216 TI - Modeling the evolution of winner and loser effects: A survey and prospectus. AB - The evolution of winner or loser effects-higher probabilities of winning after winning or of losing after losing-has received remarkably little attention from theoreticians, even though such effects are widespread across the animal kingdom. We review game-theoretic models that regard such winner and loser effects as outcomes of a strategic response. We show that these models have been well supported by the empirical literature in the past, but are not designed to address some recent observations. In the light of this recent progress on the empirical front, we identify factors that newer theory must be developed to explore. PMID- 26874217 TI - Ecoepidemic predator-prey model with feeding satiation, prey herd behavior and abandoned infected prey. AB - In this paper we analyse a predator-prey model where the prey population shows group defense and the prey individuals are affected by a transmissible disease. The resulting model is of the Rosenzweig-MacArthur predator-prey type with an SI (susceptible-infected) disease in the prey. Modeling prey group defense leads to a square root dependence in the Holling type II functional for the predator-prey interaction term. The system dynamics is investigated using simulations, classical existence and asymptotic stability analysis and numerical bifurcation analysis. A number of bifurcations, such as transcritical and Hopf bifurcations which occur commonly in predator-prey systems will be found. Because of the square root interaction term there is non-uniqueness of the solution and a singularity where the prey population goes extinct in a finite time. This results in a collapse initiated by extinction of the healthy or susceptible prey and thereafter the other population(s). When also a positive attractor exists this leads to bistability similar to what is found in predator-prey models with a strong Allee effect. For the two-dimensional disease-free (i.e. the purely demographic) system the region in the parameter space where bistability occurs is marked by a global bifurcation. At this bifurcation a heteroclinic connection exists between saddle prey-only equilibrium points where a stable limit cycle together with its basin of attraction, are destructed. In a companion paper (Gimmelli et al., 2015) the same model was formulated and analysed in which the disease was not in the prey but in the predator. There we also observed this phenomenon. Here we extend its analysis using a phase portrait analysis. For the three-dimensional ecoepidemic predator-prey system where the prey is affected by the disease, also tangent bifurcations including a cusp bifurcation and a torus bifurcation of limit cycles occur. This leads to new complex dynamics. Continuation by varying one parameter of the emerging quasi-periodic dynamics from a torus bifurcation can lead to its destruction by a collision with a saddle cycle. Under other conditions the quasi-periodic dynamics changes gradually in a trajectory that lands on a boundary point where the prey go extinct in finite time after which a total collapse of the three-dimensional system occurs. PMID- 26874218 TI - Singing on the fly: sensorimotor integration and acoustic communication in Drosophila. AB - The capacity to communicate via acoustic signals is prevalent across the animal kingdom, from insects to humans. What are the neural circuit mechanisms that underlie this ability? New methods for behavioral analysis along with an unparalleled genetic toolkit have recently opened up studies of acoustic communication in the fruit fly, Drosophila melanogaster. Its nervous system comprises roughly 100,000 neurons, yet flies are able to both produce and process time-varying sounds during courtship. Just as with more complex animals, sensory feedback plays an important role in shaping communication between the sexes. Here, we review recent work in Drosophila that has laid the foundation for solving the mechanisms by which sensory information dynamically modulates behavior. PMID- 26874220 TI - Detection of multidrug-resistant Mycobacterium tuberculosis strains isolated in Brazil using a multimarker genetic assay for katG and rpoB genes. AB - Multidrug-resistant tuberculosis (MDRTB) is a serious world health problem that limits public actions to control tuberculosis, because the most used anti tuberculosis first-line drugs fail to stop mycobacterium spread. Consequently, a quick detection through molecular diagnosis is essential to reduce morbidity and medical costs. Despite the availability of several molecular-based commercial kits to diagnose multidrug-resistant tuberculosis, their diagnostic value might diverge worldwide since Mycobacterium tuberculosis genetic variability differs according to geographic location. Here, we studied the predictive value of four common mycobacterial mutations in strains isolated from endemic areas of Brazil. Mutations were found at the frequency of 41.9% for katG, 25.6% for inhA, and 69.8% for rpoB genes in multidrug-resistant strains. Multimarker analysis revealed that combination of only two mutations ("katG/S315T+rpoB/S531L") was a better surrogate of multidrug-resistant tuberculosis than single-marker analysis (86% sensitivity vs. 62.8%). Prediction of multidrug-resistant tuberculosis was not improved by adding a third or fourth mutation in the model. Therefore, rather than using diagnostic kits detecting several mutations, we propose a simple dual marker panel to detect multidrug-resistant tuberculosis, with 86% sensitivity and 100% specificity. In conclusion, this approach (previous genetic study+analysis of only prevalent markers) would considerably decrease the processing costs while retaining diagnostic accuracy. PMID- 26874221 TI - Anaerobic digestion of biowaste under extreme ammonia concentration: Identification of key microbial phylotypes. AB - Ammonia inhibition represents a major operational issue for anaerobic digestion (AD). In order to get more insights into AD microbiota resistance, anaerobic batch reactors performances were investigated under a wide range of Total Ammonia Nitrogen (TAN) concentrations up to 50.0g/L at 35 degrees C. The half maximal inhibitory concentration (IC50) value was determined to be 19.0g/L. Microbial community dynamics revealed that above a TAN concentration of 10.0g/L, remarkable modifications within archaeal and bacterial communities occurred. 16S rRNA gene sequencing analysis showed a gradual methanogenic shift between two OTUs from genus Methanosarcina when TAN concentration increased up to 25.0g/L. Proportion of potential syntrophic microorganisms such as Methanoculleus and Treponema progressively raised with increasing TAN up to 10.0 and 25.0g/L respectively, while Syntrophomonas and Ruminococcus groups declined. In 25.0g/L assays, Caldicoprobacter were dominant. This study highlights the emergence of AD key phylotypes at extreme ammonia concentrations. PMID- 26874219 TI - Neuroimaging with magnetoencephalography: A dynamic view of brain pathophysiology. AB - Magnetoencephalography (MEG) is a noninvasive, silent, and totally passive neurophysiological imaging method with excellent temporal resolution (~1 ms) and good spatial precision (~3-5 mm). In a typical experiment, MEG data are acquired as healthy controls or patients with neurologic or psychiatric disorders perform a specific cognitive task, or receive sensory stimulation. The resulting data are generally analyzed using standard electrophysiological methods, coupled with advanced image reconstruction algorithms. To date, the total number of MEG instruments and associated users is significantly smaller than comparable human neuroimaging techniques, although this is likely to change in the near future with advances in the technology. Despite this small base, MEG research has made a significant impact on several areas of translational neuroscience, largely through its unique capacity to quantify the oscillatory dynamics of activated brain circuits in humans. This review focuses on the clinical areas where MEG imaging has arguably had the greatest impact in regard to the identification of aberrant neural dynamics at the regional and network level, monitoring of disease progression, determining how efficacious pharmacologic and behavioral interventions modulate neural systems, and the development of neural markers of disease. Specifically, this review covers recent advances in understanding the abnormal neural oscillatory dynamics that underlie Parkinson's disease, autism spectrum disorders, human immunodeficiency virus (HIV)-associated neurocognitive disorders, cerebral palsy, attention-deficit hyperactivity disorder, cognitive aging, and post-traumatic stress disorder. MEG imaging has had a major impact on how clinical neuroscientists understand the brain basis of these disorders, and its translational influence is rapidly expanding with new discoveries and applications emerging continuously. PMID- 26874222 TI - Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions? AB - Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. PMID- 26874224 TI - Identification and characterization of a heat-resistant protease from Serratia liquefaciens isolated from Brazilian cold raw milk. AB - The cold storage of raw milk before heat treatment in dairy industry promotes the growth of psychrotrophic microorganisms, which are known for their ability to produce heat-resistant proteolytic enzymes. Although Pseudomonas is described as the main causative genus for high proteolytic spoilage potential in dairy products, Serratia liquefaciens secretes proteases and may be found in raw milk samples as well. However, at the present there is no information about the proteolytic spoilage potential of S. liquefaciens in milk after heat-treatment. The main aim of this research was to assess the proteolytic spoilage potential of S. liquefaciens isolated from Brazilian raw milk and to characterize the involved protease. S. liquefaciens was shown to secrete one heat-resistant spoilage metalloprotease of, approximately, 52 kDa encoded by the ser2 gene. The heat resistance of Ser2 was similar to the aprX encoded metalloprotease produced by Pseudomonas. Although the ser2 gene was detected in all S. liquefaciens isolates tested in this study, the proteolytic activity of the isolates in milk was highly heterogeneous. Since nucleotide and deduced amino acid sequences of ser2 of all tested isolates are identical, this heterogeneity may be attributed to differences in enzyme expression levels or post-translational modifications. PMID- 26874225 TI - Radiation dose estimation for marine mussels following exposure to tritium: Best practice for use of the ERICA tool in ecotoxicological studies. AB - Accurate dosimetry is critically important for ecotoxicological and radioecological studies on the potential effects of environmentally relevant radionuclides, such as tritium ((3)H). Previous studies have used basic dosimetric equations to estimate dose from (3)H exposure in ecologically important organisms, such as marine mussels. This study compares four different methods of estimating dose to adult mussels exposed to 1 or 15 MBq L(-1) tritiated water (HTO) under laboratory conditions. These methods were (1) an equation converting seawater activity concentrations to dose rate with fixed parameters; (2) input into the ERICA tool of seawater activity concentrations only; (3) input into the ERICA tool of estimated whole organism concentrations (woTACs), comprising dry activity plus estimated tissue free water tritium (TFWT) activity (TFWT volume * seawater activity concentration); and (4) input into the ERICA tool of measured whole organism activity concentrations, comprising dry activity plus measured TFWT activity (TFWT volume * TFWT activity concentration). Methods 3 and 4 are recommended for future ecotoxicological experiments as they produce values for individual animals and are not reliant on transfer predictions (estimation of concentration ratio). Method 1 may be suitable if measured whole organism concentrations are not available, as it produced results between 3 and 4. As there are technical complications to accurately measuring TFWT, we recommend that future radiotoxicological studies on mussels or other aquatic invertebrates measure whole organism activity in non-dried tissues (i.e. incorporating TFWT and dry activity as one, rather than as separate fractions) and input this data into the ERICA tool. PMID- 26874223 TI - Molecular, cellular and functional events in axonal sprouting after stroke. AB - Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: reactive, reparative and unbounded axonal sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair. PMID- 26874226 TI - Statistical mechanics of neocortical interactions: Large-scale EEG influences on molecular processes. AB - Calculations further support the premise that large-scale synchronous firings of neurons may affect molecular processes. The context is scalp electroencephalography (EEG) during short-term memory (STM) tasks. The mechanism considered is Pi=p+qA (SI units) coupling, where p is the momenta of free Ca(2+) waves, q the charge of Ca(2+) in units of the electron charge, and A the magnetic vector potential of current I from neuronal minicolumnar firings considered as wires, giving rise to EEG. Data has processed using multiple graphs to identify sections of data to which spline-Laplacian transformations are applied, to fit the statistical mechanics of neocortical interactions (SMNI) model to EEG data, sensitive to synaptic interactions subject to modification by Ca(2+) waves. PMID- 26874227 TI - T cell and reticular network co-dependence in HIV infection. AB - Fibroblastic reticular cells (FRC) are arranged on a network in the T cell zone of lymph nodes, forming a scaffold for T cell migration, and providing survival factors, especially interleukin-7 (IL-7). Conversely, CD4(+) T cells are the major producers of lymphotoxin-beta (LT-beta), necessary for the construction and maintenance of the FRC network. This interdependence creates the possibility of a vicious cycle, perpetuating loss of both FRC and T cells. Furthermore, evidence that HIV infection is responsible for collagenation of the network suggests that long term loss of network function might be responsible for the attenuated recovery in T cell count seen in HIV patients undergoing antiretroviral therapy (ART). We present computational and mathematical models of this interaction mechanism and subsequent naive CD4(+) T-cell depletion in which (1) collagen deposition impedes access of naive T cells to IL-7 on the FRC and loss of IL-7 production by loss of FRC network itself, leading to the depletion of naive T cells through increased apoptosis; and (2) depletion of naive T cells as the source of LT-beta on which the FRC depend for survival leads to loss of the network, thereby amplifying and perpetuating the cycle of depletion of both naive T cells and stromal cells. Our computational model explicitly includes an FRC network and its cytokine exchange with a heterogeneous T-cell population. We also derive lumped models, in terms of partial differential equations and reduced to ordinary differential equations, that provide additional insight into the mechanisms at work. The central conclusions are that (1) damage to the reticular network, caused by HIV infection is a plausible mechanism for attenuated recovery post-ART; (2) within this, the production of T cell survival factors by FRCs may be the key rate-limiting step; and (3) the methods of model reduction and analysis presented are useful for both immunological studies and other contexts in which agent-based models are severely limited by computational cost. PMID- 26874228 TI - Experimental measurements and mathematical modeling of biological noise arising from transcriptional and translational regulation of basic synthetic gene circuits. AB - The small number of molecules, unevenly distributed within an isogenic cell population, makes gene expression a noisy process, and strategies have evolved to deal with this variability in protein concentration and to limit its impact on cellular behaviors. As translational efficiency has a major impact on biological noise, a possible strategy to control noise is to regulate gene expression processes at the post-transcriptional level. In this study, fluctuations in the concentration of a green fluorescent protein were compared, at the single cell level, upon transformation of an isogenic bacterial cell population with synthetic gene circuits implementing either a transcriptional or a post transcriptional control of gene expression. Experimental measurements showed that protein variability is lower under post-transcriptional control, when the same average protein concentrations are compared. This effect is well reproduced by stochastic simulations, supporting the hypothesis that noise reduction is due to the control mechanism acting on the efficiency of translation. Similar strategies are likely to play a role in noise reduction in natural systems and to be useful for controlling noise in synthetic biology applications. PMID- 26874229 TI - Application of ionic liquids in vacuum microwave-assisted extraction followed by macroporous resin isolation of three flavonoids rutin, hyperoside and hesperidin from Sorbus tianschanica leaves. AB - Rutin, hyperoside and hesperidin were effectively extracted from Sorbus tianschanica leaves by an ionic liquid vacuum microwave-assisted method. A series of ionic liquids with various anions and alkyl chain length of the cations were studied and the extraction was performed in [C6mim][BF4] aqueous solution. After optimization by a factorial design and response surface methodology, total extraction yield of 2.37mg/g with an error of 0.12mg/g (0.71+/-0.04mg/g, 1.18+/ 0.06mg/g and 0.48+/-0.02 for rutin, hyperoside and hesperidin, respectively) was achieved under -0.08MPa for vacuum, 19min and 420W for microwave irradiation time and power, and 15mL/g for liquid-solid ratio. The proposed method here is more efficient and needs a shorter extraction time for rutin, hyperoside and hesperidin from S. tianschanica leaves than reference extraction techniques. In stability studies performed with standard rutin, hyperoside and hesperidin, the target analytes were stable under the optimum conditions. The proposed method had a high reproducibility and precision. In addition, separation of rutin, hyperoside and hesperidin from [C6mim][BF4] extraction solution was completed effectively by AB-8 macroporous resin adsorption and desorption process. Ionic liquid vacuum microwave-assisted extraction is a simple, rapid and efficient sample extraction technique. PMID- 26874230 TI - Use of the Houghton Scale to Classify Community and Household Walking Ability in People With Lower-Limb Amputation: Criterion-Related Validity. AB - OBJECTIVE: To examine the criterion-related validity of using the self-reported Houghton Scale to classify community-dwelling people with lower-limb amputation according to the suggested score ranges for independent community (Houghton Scale score >=9), household and limited community (Houghton Scale scores 6-8), and limited household (Houghton Scale score <=5) walking ability categories as referenced to performance-based balance ability and walking speed criteria. DESIGN: Cross-sectional cohort study. SETTING: Community-based wellness walking programs in 8 states in the Mid-Atlantic, Midwest, and Southeast regions of the U.S. PARTICIPANTS: Volunteers (N=180; 66.5% men, n=118; mean age, 55.5+/-16y) 7.1+/-13.1 years since amputation, with transtibial-level amputation in 47% (n=79) and amputation caused by vascular disease in 49.4% (n=89). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Self-reported data: Houghton Scale, Prosthetic Evaluation Questionnaire mobility subscale, and Activities-specific Balance Confidence (ABC) Scale. Clinical performance-based measures: balance ability assessed with 3 Berg Balance Scale (BBS) items and walking ability assessed with the timed Up and Go (TUG) test and 2-minute walk test (2MWT). The primary reference criteria were performance-based balance ability measured with the 3 BBS items and gait speed calculated from the 2MWT. RESULTS: On the Houghton Scale, 45.9% (78/170) of the participants scored >=9, 30.6% (52/170) of the participants scored between 6 and 8, and 23.5% (40/170) of the participants scored <=5. The Houghton Scale correlated with the Prosthetic Evaluation Questionnaire mobility subscale (r=.73), ABC Scale (r=.76), balance ability (r=.67), TUG test (r=-.67), and 2MWT (r=.73). The 3 Houghton Scale ability categories differed significantly from each other (P<.05) for all outcome measures: Prosthetic Evaluation Questionnaire mobility subscale, ABC Scale, balance ability, TUG test, and 2MWT. CONCLUSIONS: The Houghton Scale demonstrated criterion-related validity by differentiating community-dwelling people with lower-limb amputation into community, limited community/household, and household ability categories that corresponded to performance-based balance and walking criteria. Average prosthetic walking speeds for each category compared with similar walking ability categories defined in other patient populations. PMID- 26874231 TI - Caregiver Factors in Stroke: Are They the Missing Piece of the Puzzle? AB - Stroke is a major global health problem and a leading cause of long-term disability. As health care professionals working with these patients, we work closely with their caregivers because we recognize the crucial role they play in our patients' recovery. Increasingly, the effect of patient factors on caregiver outcomes is being studied. However, the effect of the reverse relationship of caregiver factors on patient outcomes has received much less attention, although there is evidence that social and family support can positively (and sometimes negatively) affect patient outcomes. A better understanding of this relationship may have implications for rehabilitation research, professional practice, and policy directions in terms of resource allocation. PMID- 26874232 TI - Task-Dependent Bimanual Coordination After Stroke: Relationship With Sensorimotor Impairments. AB - OBJECTIVES: To determine (1) bimanual coordination deficits in patients with stroke using 3-dimensional kinematic analyses as they perform naturalistic tasks requiring collaborative interaction of the 2 arms; and (2) whether bimanual coordination deficits are related to clinical measures of sensorimotor impairments and unimanual performance of the paretic arm. DESIGN: Case-control study. SETTING: Rehabilitation hospital research institute. PARTICIPANTS: Participants (N=24) were patients with unilateral chronic stroke (n=14) and age matched controls (n=10). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Temporal coordination between the 2 hands as participants performed (1) a symmetric task: reach to pick up a box using both hands; and (2) an asymmetric task: open a drawer with 1 hand to press a button inside with the other hand. RESULTS: During the symmetric task, patients and controls showed preserved temporal coupling while transporting the hands to the box. However, on reaching the box, patients demonstrated an impaired ability to cooperatively interact their 2 arms for an efficient pickup. This led to significantly longer pickup times compared with controls. Pickup time positively correlated with proprioceptive deficits of the paretic arm. During the asymmetric task, patients had a longer time delay between drawer opening and button pressing movements than controls. The deficits in asymmetric coordination did not significantly correlate with sensorimotor impairments or unimanual paretic arm performance. CONCLUSIONS: Bimanual coordination was impaired in patients poststroke during symmetric and asymmetric bimanual tasks that required cooperative interaction between the 2 arms. While the proprioceptive system contributes to symmetric cooperative coordination, commonly tested measures of paretic arm impairment or performance, or both, do not strongly predict deficits in bimanual coordination. PMID- 26874233 TI - Do we really care about unintended outcomes? An analysis of evaluation theory and practice. AB - The concept of 'unintended outcomes' has a long history. Contributions to the topic have appeared under the guise of various disciplinary lenses, including programme evaluation. There is now solid consensus among the international evaluation community regarding the need to consider side effects as a key aspect in any evaluative study. However, this concern often equates to nothing more than false piety. In this article, shortcomings of existing theoretical developments to evaluate unintended outcomes are identified. Current evaluation practices in international development are then analysed to demonstrate ways in which unintended outcomes remain peripheral. Reasons for neglect are discussed and the need for a stronger re-focusing on unintended effects of development interventions is advocated. PMID- 26874234 TI - Why so many "rigorous" evaluations fail to identify unintended consequences of development programs: How mixed methods can contribute. AB - Many widely-used impact evaluation designs, including randomized control trials (RCTs) and quasi-experimental designs (QEDs), frequently fail to detect what are often quite serious unintended consequences of development programs. This seems surprising as experienced planners and evaluators are well aware that unintended consequences frequently occur. Most evaluation designs are intended to determine whether there is credible evidence (statistical, theory-based or narrative) that programs have achieved their intended objectives and the logic of many evaluation designs, even those that are considered the most "rigorous," does not permit the identification of outcomes that were not specified in the program design. We take the example of RCTs as they are considered by many to be the most rigorous evaluation designs. We present a numbers of cases to illustrate how infusing RCTs with a mixed-methods approach (sometimes called an "RCT+" design) can strengthen the credibility of these designs and can also capture important unintended consequences. We provide a Mixed Methods Evaluation Framework that identifies 9 ways in which UCs can occur, and we apply this framework to two of the case studies. PMID- 26874235 TI - Measuring program- and individual-level fidelity in a home visiting program for adolescent parents. PMID- 26874236 TI - Multiplex bead-based immunoassay for the free soluble forms of the HLA-G receptors, ILT2 and ILT4. AB - Human leukocyte antigen (HLA)-G is an immune-inhibitory molecule that exerts its function via interaction with two main inhibitory receptors: ILT2 and ILT4. This interaction is considered to be an immune checkpoint. HLA-G can be found as a soluble molecule, but it is not known if its receptors can also be found as soluble molecules. In this work, we present a multiplex luminex-based assay to measure soluble ILT2 (sILT2) and soluble ILT4 (sILT4) molecules together. It is based on two antibody pairs, GHI/75 and HP-F1-PE for ILT2 and 27D6 and 42D1-PE for ILT4. The characterization of our method reveals that it specifically detects the free soluble forms of sILT2 and sILT4, and not those complexed to HLA Class I molecules such as their ligand of highest affinity HLA-G. A study on two small cohorts of cancer patients demonstrated that soluble ILT2 and ILT4 molecules were of low abundance in the plasma of healthy controls, but that elevated levels of plasmatic sILT2 were present in non-muscle-infiltrating bladder cancer patients. This demonstrated that the titration test is indeed working, and that soluble ILT2 molecules do exist in pathological contexts, which relevance may now be sought on larger cohorts and other pathologies. PMID- 26874237 TI - Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response. AB - Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response. PMID- 26874238 TI - Preterm uterine contractions ultimately delivered at term: safe but not out of danger. AB - OBJECTIVES: Patients with pregnancies complicated with premature uterine contractions (PMC), but delivered at term are considered as false preterm labor (PTL), and represent a common obstetric complication. We aimed to assess obstetric and neonatal outcomes of pregnancies complicated with PMC, but delivered at term, as compared to term normal pregnancies. STUDY DESIGN: Obstetric, maternal and neonatal outcomes of singleton pregnancies complicated with PMC between 24-33(6)/7 weeks (PMC group), necessitating hospitalization and treatment with tocolytics and/or steroids, during 2009-2014, were reviewed. The study group included only cases who eventually delivered >=37 weeks, which were compared to a control group of subsequent term singleton deliveries who had not experienced PMC during pregnancy. Neonatal adverse composite outcome included: phototherapy, RDS, sepsis, blood transfusion, cerebral injury, NICU admission. RESULTS: The PMC group (n=497) was characterized by higher rates of nulliparity (p=0.002), infertility treatments (p=0.02), and polyhydramnios (p<0.001), as compared to controls (n=497). Labor was characterized by higher rates of instrumental deliveries (p=0.03), non-reassuring fetal heart rate tracings (p<0.001) prolonged third stage of labor (p=0.04), and increased rate of post partum maternal anemia (Hb<8g/dL) p=0.004, in the PMC group as compared to controls. Neonates in the PMC groups had lower birth weights compared to controls, 3149g+/-429 vs. 3318g+/-1.1, p<0.001, respectively. By logistic regression analysis, PMC during pregnancy was independently associated with neonatal birth-weight <3rd percentile (adjusted OR 4.6, 95% CI 1.5-13.7). CONCLUSIONS: Pregnancies complicated with PMC, even-though delivered at term, entail adverse obstetric and neonatal outcomes, and may warrant continued high risk follow up. PMID- 26874240 TI - Corrigendum to "Calcium release-activated calcium (CRAC) channels mediate the beta2 -adrenergic regulation of Na,K-ATPase" [FEBS Lett. 588 (24) (2014) 4686 4693]. PMID- 26874239 TI - Are coping strategies and locus of control orientation associated with health related quality of life in older adults with and without depression? AB - The aim of this study was to investigate relationships between coping and health related quality of life (HRQoL) in older adults (aged >=60 years) with and without depression. This cross-sectional study included 144 depressed inpatients from seven psychogeriatric hospital units in Norway and 106 community-living older adults without depression. HRQoL was measured using Euro Qol Group's EQ-5D Index and visual analog scale (EQ-VAS). Two aspects of coping were of primary interest for HRQoL: locus of control (LOC) and ways of coping (WOC). Measures of depressive symptoms, cognitive functioning, instrumental activities of daily living, and general physical health were included as covariates. In linear regression analyses adjusted for age, stronger external LOC was associated with poorer HRQoL in both depressed and non-depressed older adults. In the fully specified regression models for both groups, the association between stronger external LOC and poorer HRQoL remained significant for the EQ-VAS score but not the EQ-5D Index. WOC was not associated with HRQoL in either group. Total amount of explained variance in fully-specified models was considerably lower in the sample of depressed, hospitalized older adults (17.1% and 15.5% for EQ-5D index and EQ-VAS, respectively), than in the sample of non-depressed, community-based older adults (45.8% and 48.9% for EQ-5D Index and EQ-VAS, respectively). One aspect of coping (LOC orientation) was associated with HRQoL in both depressed and non-depressed older adult samples, and therefore may be an important target for intervention for both groups. Differences in the amount of variance explained in models for the two groups warrant further research. PMID- 26874242 TI - Extracurricular participation among children with epilepsy in Canada. AB - INTRODUCTION: Participation in extracurricular activities creates opportunities for children to foster friendships, promote a sense of belonging, and improve physical and mental well-being. The objective of this study was to determine the relationship(s) of personal factors, seizure variables, and social supports with extracurricular participation in children with epilepsy (CWE). METHODS: Baseline analysis of the QUALITE longitudinal study cohort of children aged 8-14 years (N=426) was conducted. Variables hypothesized to be related to the participation of CWE were classified using the International Classification of Functioning, Disability and Health according to body functions (presence of generalized tonic clonic seizures in the past month, on/off AEDs, and seizure severity), environmental factors (perceived social support from parents and friends), and personal factors (sex, age, family structure, and family income). Analysis of variables related to extracurricular participation was conducted with regression modeling. RESULTS: Personal factors of age, gender, and family structure as well as body function variables of generalized tonic-clonic seizures and seizure severity were found to be the most important to extracurricular participation based on how frequently they were included in the final models (16/16 and 13/16 times, respectively). When parental support was found to be related to participation, the association was negative in 6 out of 16 models. DISCUSSION: The personal factors that are related to extracurricular participation among children with epilepsy mirror samples based on the general population, although seizures also play an important role. The relationship between perceived parental support and actual participation levels warrants further exploration. PMID- 26874243 TI - Psychiatric comorbidity in psychogenic nonepileptic seizures compared with epilepsy. AB - OBJECTIVES: Psychogenic nonepileptic seizures (PNESs) are closely linked with psychological distress, but their etiology is not well-understood. We reviewed psychiatric comorbidity in PNESs and epileptic seizures (ESs) with an aim to assist understanding, diagnosis, and management of PNESs. METHODS: A search of Web of Science, MEDLINE (PubMed), PsycINFO, and Scopus identified 32 relevant studies on the prevalence of psychiatric comorbidity in PNESs. We used meta analysis to compare psychiatric comorbidity between PNESs and ESs. RESULTS: Samples with PNESs had high rates of psychiatric comorbidity overall (53-100%), notably including posttraumatic stress disorder (PTSD), depression, and personality and anxiety disorders. Compared with ESs, samples with PNESs had more psychiatric comorbidity overall (RR: 1.30, 95% CI: 1.14-1.48, p<0.0001) with significantly elevated risks found for PTSD, personality disorder, and anxiety but not depression. CONCLUSIONS: Psychiatric disorders are more common in PNESs than ESs. Because of methodological limitations of available studies, causality cannot be established; prospective longitudinal designs are required. PMID- 26874244 TI - Metabolite signature for diagnosing major depressive disorder in peripheral blood mononuclear cells. AB - BACKGROUND: Major depressive disorder (MDD) is a serious debilitating psychiatric disorder. However, the molecular mechanisms of MDD remain largely unknown, and no objective laboratory-based tests are available to diagnose this disorder. METHODS: A gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was used to compare peripheral blood mononuclear cells (PBMC) metabolic profiling of 50 first onset drug-naive MDD subjects and 50 healthy controls (training samples), to identify potential metabolite biomarkers for MDD. An independent sample cohort including 58 MDD patients, 40 schizophrenia (SCZ) patients and 56 healthy controls (test samples) was used to validate diagnostic generalizability and specificity of identified biomarkers. RESULTS: 17 PBMC metabolites responsible for discriminating MDD group from healthy control group were identified. These metabolites were mainly involved in disturbances of energy and neurotransmitter metabolism. This PBMC metabolite signature could effectively discriminate MDD subjects from the healthy controls with an AUC of 0.926 in training samples and 0.870 in test samples. Moreover, this metabolite signature enabled distinguishing MDD subjects from schizophrenia subjects with an AUC of 0.899. LIMITATIONS: This study was limited by potential confounding effects of different drug treatments in some MDD and schizophrenia subjects, and lack of animal studies to further validate the identified metabolite pathways in MDD. CONCLUSION: These findings suggest that early disturbances of PBMC energy and neurotransmitter metabolism may be associated with the onset of MDD. This PBMC metabolite signature may facilitate development of a laboratory-based diagnostic test for MDD. PMID- 26874245 TI - Top 10 research questions to promote physical activity in bipolar disorders: A consensus statement from the International Organization of Physical Therapists in Mental Health. AB - BACKGROUND: Research has only recently started to consider the importance and applicability of physical activity (PA) for people with bipolar disorder (BD). The aim of the current study is to highlight 10 pertinent PA research questions in people with BD. METHODS: The International Organization of Physical Therapy in Mental Health executed a consultation with all National organizations (n=13) to identify the most salient questions to guide future research on PA in BD. RESULTS: We identified the following 10 questions: (1) What are the benefits of PA for people with BD? (2) What are the most prominent safety issues for PA prescription in BD? (3) What is the optimal PA prescription for people with BD? (4) What are the key barriers to PA among people with BD? (5) What are the most effective motivational strategies for ensuring PA adoption and maintenance in BD? (6) How do we translate PA research into community practice? (7) If one treatment goal is increased physical activity, what type of professionals are needed as part of a multidisciplinary team? (8) How do we incorporate PA as a vital sign in clinical practice? (9) How can we prevent sedentary behavior in BD? (10) What is the most appropriate PA assessment method? LIMITATIONS: We did not consult people with BD. CONCLUSIONS: Addressing these questions is critical for developing evidence-based approaches for promoting and sustaining an active lifestyle in BD. Ultimately, achieving this will reduce the burden of cardiovascular disease and improve the quality of life of this population. PMID- 26874247 TI - Prolonged propofol infusion for mechanically ventilated children. AB - We retrospectively analysed 30-day mortality and duration of intubation for 8016 children ventilated for three or more days, sedated with midazolam (n = 7716) or propofol (n = 300). We matched the propensity scores of 263 pairs of children. The propensity-matched 30-day mortality (95% CI) was similar: 17/263 (6.5%) with midazolam vs. 24/263 (9.1%) with propofol, p = 0.26. Weaning from mechanical ventilation of children sedated with midazolam was slower than weaning of children sedated with propofol, subhazard ratio (95% CI) 1.43 (1.18-1.73), p < 0.001. PMID- 26874246 TI - Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neck. AB - BACKGROUND: Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy. METHODS: Eighty-four cases of ACC were identified, the CTAs pan Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data. RESULTS: Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p = .096). Patients expressing both NY ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p = .047). CONCLUSION: A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1008-1016, 2016. PMID- 26874248 TI - Microscopic anthropogenic litter in terrestrial birds from Shanghai, China: Not only plastics but also natural fibers. AB - The level of contamination by microscopic anthropogenic litter (0.5-5mm) in terrestrial ecosystems is not well understood. After chemical digestion in 10% KOH, microscopic anthropogenic litter from the gastrointestinal tracts of 17 terrestrial birds was identified and categorized under a stereomicroscope based on its physical properties and melting tests. In total, 364 items from 16 birds were identified as microscopic anthropogenic litter, ranging in size from 0.5 to 8.5mm. No relationship between plastic load and body condition was found. Natural fibers, plastic fibers and fragmented plastics represented, respectively, 37.4% (136 items), 54.9% (200 items) and 7.7% (28 items) of total litter items. Small sample sizes limited our ability to draw strong conclusions about the metabolism of natural fibers, but the decline in the proportion of natural fibers from the esophagus to stomach to intestine suggested that they may be digestible. Particles smaller than 5mm represented more than 90% of the total number of pollutant items. Particles with colors in the mid-tones and fibrous shapes were overwhelmingly common particles. The results reflect pollution by microscopic anthropogenic litter in the terrestrial ecosystem of the study area. Microscopic natural fibers, which may disperse and adsorb chemical pollutants differently from microplastic and may pose an even greater risk, are in urgent need of further research. PMID- 26874249 TI - GEP-based method to formulate adhesion strength and hardness of Nb PVD coated on Ti-6Al-7Nb aimed at developing mixed oxide nanotubular arrays. AB - PVD process as a thin film coating method is highly applicable for both metallic and ceramic materials, which is faced with the necessity of choosing the correct parameters to achieve optimal results. In the present study, a GEP-based model for the first time was proposed as a safe and accurate method to predict the adhesion strength and hardness of the Nb PVD coated aimed at growing the mixed oxide nanotubular arrays on Ti67. Here, the training and testing analysis were executed for both adhesion strength and hardness. The optimum parameter combination for the scratch adhesion strength and micro hardness was determined by the maximum mean S/N ratio, which was 350W, 20 sccm, and a DC bias of 90V. Results showed that the values calculated in the training and testing in GEP model were very close to the actual experiments designed by Taguchi. The as sputtered Nb coating with highest adhesion strength and microhardness was electrochemically anodized at 20V for 4h. From the FESEM images and EDS results of the annealed sample, a thick layer of bone-like apatite was formed on the sample surface after soaking in SBF for 10 days, which can be connected to the development of a highly ordered nanotube arrays. This novel approach provides an outline for the future design of nanostructured coatings for a wide range of applications. PMID- 26874250 TI - Cell elasticity with altered cytoskeletal architectures across multiple cell types. AB - The cytoskeleton is primarily responsible for providing structural support, localization and transport of organelles, and intracellular trafficking. The structural support is supplied by actin filaments, microtubules, and intermediate filaments, which contribute to overall cell elasticity to varying degrees. We evaluate cell elasticity in five different cell types with drug-induced cytoskeletal derangements to probe how actin filaments and microtubules contribute to cell elasticity and whether it is conserved across cell type. Specifically, we measure elastic stiffness in primary chondrocytes, fibroblasts, endothelial cells (HUVEC), hepatocellular carcinoma cells (HUH-7), and fibrosarcoma cells (HT 1080) subjected to two cytoskeletal destabilizers: cytochalasin D and nocodazole, which disrupt actin and microtubule polymerization, respectively. Elastic stiffness is measured by atomic force microscopy (AFM) and the disruption of the cytoskeleton is confirmed using fluorescence microscopy. The two cancer cell lines showed significantly reduced elastic moduli values (~0.5kPa) when compared to the three healthy cell lines (~2kPa). Non-cancer cells whose actin filaments were disrupted using cytochalasin D showed a decrease of 60-80% in moduli values compared to untreated cells of the same origin, whereas the nocodazole-treated cells showed no change in elasticity. Overall, we demonstrate actin filaments contribute more to elastic stiffness than microtubules but this result is cell type dependent. Cancer cells behaved differently, exhibiting increased stiffness as well as stiffness variability when subjected to nocodazole. We show that disruption of microtubule dynamics affects cancer cell elasticity, suggesting therapeutic drugs targeting microtubules be monitored for significant elastic changes. PMID- 26874251 TI - Breast cancer cells mechanosensing in engineered matrices: Correlation with aggressive phenotype. AB - The pathogenesis of cancer is often driven by the modulation of the tumor microenvironment. Recent reports have highlighted that the progressive stiffening of tumor matrix is crucial for malignant transformation. Though extensive work has been done analyzing the mechanotransductive signals involved in tumor progression, it is still not clear whether the stiffness induced changes in cancer cell behavior is conserved across the invasive/aggressive phenotype of cells. Here, we used synthetic hydrogel based cell culture platform to correlate the aggressive potential of the breast cancer cells to the responses to matrix stiffness. The cellular functions such as proliferation, migration, and angiogenic capability were characterized. We report that the proliferation and motility of the highly aggressive cell line MDA-MB-231 increased with increase in matrix rigidity. We also demonstrated for the first time that the change in matrix stiffness stimulated the angiogenic activity of these cells as manifested from enhanced expression of vascular endothelial growth factor (VEGF). Inhibition of actomyosin contractility attenuated proliferation of MDA-MB-231 cells on stiff matrices while promoted the growth on soft gels. In addition, the release of VEGF was reduced upon inhibition of contractility. The less and non-aggressive breast cancer cells, SKBr3 and MCF-7 respectively displayed less dependency on matrix stiffness. PMID- 26874252 TI - Modelling of residually stressed materials with application to AAA. AB - Residual stresses are generated in living tissues by processes of growth and adaptation and they significantly influence the mechanical behaviour of the tissues. Thus, to effectively model the elastic response of the tissues relative to a residually stressed configuration the residual stresses need to be incorporated into the constitutive equations. The purposes of this paper are (a) to summarise a general elastic constitutive formulation that includes residual stress, (b) to specify the tensors needed for the three-dimensional implementation of the theory in a nonlinear finite element code, and (c) to use the theory and its implementation to evaluate the wall stress distribution in an abdominal aortic aneurysm (AAA) using patient specific geometry and material model parameters. The considered material is anisotropic with two preferred directions indicating the orientation of the collagen fibres in the aortic tissue. The method described in this paper is general and can be used, by specifying appropriate energy functions, to investigate other residually stressed biological systems. PMID- 26874253 TI - Eutrophication mediates a common off-flavor compound, 2-methylisoborneol, in a drinking water reservoir. AB - Off-flavors, such as 2-methylisoborneol (MIB) and geosmin, cause drinking water to have earthy or musty tastes and odors. Humans can detect such compounds at minute concentrations (10 and 30 ng/L for MIB and geosmin, respectively), and, although not a health risk, off-flavors can promote consumer distrust. Removal of these compounds is costly and often unreliable or only suitable under certain conditions. Minimizing off-flavor production at the watershed-scale may be more cost-effective in addition to improving ecosystem health and aesthetics. Cyanobacteria are considered to be the primary drivers of off-flavors in freshwater systems. Due to their ability to produce toxins, cyanobacteria have been under particular scrutiny, and environmental factors promoting cyanobacterial blooms are relatively well-studied. Using this body of literature, we conducted a seven-week, limnocorral experiment where we manipulated nitrogen and nitrogen-to-phosphorus concentrations to influence phytoplankton community structure and off-flavor production. The addition of a single nutrient across broad ranges (nitrogen or phosphorus) had no effect on MIB. However, the addition of both nitrogen and phosphorus promoted high concentrations of MIB relative to treatments that received no nutrients (448% increase) or only nitrogen or phosphorus (722% increase). Interestingly, cyanobacteria waned during the experiment and were replaced by diatoms, which were the dominant taxa by the end of the experiment. Our findings clearly show that eutrophication affects MIB production, but mechanisms leading to the production of this compound may differ from what has been previously predicted. PMID- 26874254 TI - Use of dual carbon-chlorine isotope analysis to assess the degradation pathways of 1,1,1-trichloroethane in groundwater. AB - Compound-specific isotope analysis (CSIA) is a powerful tool to track contaminant fate in groundwater. However, the application of CSIA to chlorinated ethanes has received little attention so far. These compounds are toxic and prevalent groundwater contaminants of environmental concern. The high susceptibility of chlorinated ethanes like 1,1,1-trichloroethane (1,1,1-TCA) to be transformed via different competing pathways (biotic and abiotic) complicates the assessment of their fate in the subsurface. In this study, the use of a dual C-Cl isotope approach to identify the active degradation pathways of 1,1,1-TCA is evaluated for the first time in an aerobic aquifer impacted by 1,1,1-TCA and trichloroethylene (TCE) with concentrations of up to 20 mg/L and 3.4 mg/L, respectively. The reaction-specific dual carbon-chlorine (C-Cl) isotope trends determined in a recent laboratory study illustrated the potential of a dual isotope approach to identify contaminant degradation pathways of 1,1,1-TCA. Compared to the dual isotope slopes (Deltadelta(13)C/Deltadelta(37)Cl) previously determined in the laboratory for dehydrohalogenation/hydrolysis (DH/HY, 0.33 +/- 0.04) and oxidation by persulfate (infinity), the slope determined from field samples (0.6 +/- 0.2, r(2) = 0.75) is closer to the one observed for DH/HY, pointing to DH/HY as the predominant degradation pathway of 1,1,1-TCA in the aquifer. The observed deviation could be explained by a minor contribution of additional degradation processes. This result, along with the little degradation of TCE determined from isotope measurements, confirmed that 1,1,1-TCA is the main source of the 1,1-dichlorethylene (1,1-DCE) detected in the aquifer with concentrations of up to 10 mg/L. This study demonstrates that a dual C-Cl isotope approach can strongly improve the qualitative and quantitative assessment of 1,1,1-TCA degradation processes in the field. PMID- 26874255 TI - An insight on the alkaloid content of Capparis spinosa L. root by HPLC-DAD-MS, MS/MS and (1)H qNMR. AB - The Capparis spinosa L. has a wide distribution in the Old World from South Europe, North and East Africa, Madagascar, Southwest and Central Asia to Australia and Oceania. The consolidated traditional use of C. spinosa root as remedy against different pains in human is well known since the antiquity. Various secondary metabolites have been found in caper plant, nevertheless, few studies have been focused to the analysis of root constituents. To date, several free and glycosilated spermidine alkaloids and a more polar alkaloid, the stachydrine, have been isolated from the root of C. spinosa. Aim of this work was to improve the knowledge on the alkaloid content of the root of a Syrian sample of C. spinosa by HPLC-DAD-MS(n) and to propose methods to quantify these molecules in different raw extracts. A decoction, an hydroalcoholic extraction and a fractionation process to selectively recover the spermidine alkaloids were applied. To our knowledge, this is the first HPLC-DAD-MS(n) profile that pointed out the co-presence of stachydrine, several isobaric forms of capparispine and/or capparisine in free and glycosylated forms and some isobars of isocodonocarpine or codonocarpine as monoglycosides in extracts of C. spinosa root. The determination by HPLC/DAD for the spermidine alkaloids expressed as p-OH-coumaric acid gave values up to 3.5mg/g dried root and the stachydrine evaluated by (1)H NMR was close to 12.5mg/g dried root. Overall, the total alkaloids were almost doubled in hydroalcoholic extract with respect to the decoction, and the stachydrine in the cortex was almost double than in the whole root. PMID- 26874256 TI - Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats. AB - Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. PMID- 26874257 TI - Characterization and identification of isoflavonoid glycosides in the root of Spiny restharrow (Ononis spinosa L.) by HPLC-QTOF-MS, HPLC-MS/MS and NMR. AB - Restharrow root has been used in traditional medicine for thousands of years; however, the active ingredients responsible for the diuretic effect are still unknown. Previous studies have proved that the root extract contains isoflavonoids, however only few derivatives were identified, mostly relying on retention times or UV data. The aim of our work was to perform a detailed structural characterization of the complete isoflavonoid profile in the aqueous methanolic extract of Ononis spinosa root by high-performance liquid chromatography coupled with electrospray ionization accurate-mass quadrupole time of-flight and tandem mass spectrometry in positive ionization mode (HPLC-ESI-QTOF MS, HPLC-ESI-MS/MS) and nuclear magnetic resonance spectroscopy (NMR). On the basis of the accurate masses and fragmentation patterns isoflavones (formononetin, calycosin and pseudobaptigenin) and pterocarpans (maackiain and medicarpin) were identified. Two further dihydroisoflavone aglycones, namely onogenin and sativanone and a unique glucoside were isolated and their structures were elucidated by NMR experiments. Calycosin, onogenin and sativanone were detected in this plant for the first time. In contrast to previous works, the presence of biochanin A could not be confirmed, however its regioisomer calycosin and its derivatives were identified. Similarly, neither tectorigenin derivatives could be detected, however the isobar compound sativanone and its various glucosides were elucidated. The presence of genistein and daidzein could not be confirmed in the extract. Fragmentation pathways for onogenin and sativanone are presented. In the aqueous-methanolic extract 9 glucosides, 6 minor and 8 major glucoside malonates, 4 glucoside acetates and 7 aglycones were found. In total, 34 compounds were successfully identified. PMID- 26874258 TI - Optimum dose of neostigmine to reverse shallow neuromuscular blockade with rocuronium and cisatracurium. AB - We examined the use of neostigmine for reversing shallow (defined as train-of four ratio of 0.5), cisatracurium- and rocuronium-induced neuromuscular block in 112 patients, by use of 0 MUg.kg(-1) , 10 MUg.kg(-1) , 20 MUg.kg(-1) or 40 MUg.kg(-1) dose of neostigmine for reversal. The times from neostigmine administration to train-of-four ratios of 0.7, 0.9 and 1.0 were evaluated. Analysis of variance showed that the duration of action was significantly longer after cisatracurium compared with rocuronium. The time to reach a train-of-four ratio of 1.0 was significantly shorter with neostigmine 40 MUg.kg(-1) compared with lower neostigmine doses, and at this dose the time did not differ between cisatracurium and rocuronium. The recovery time from a train-of-four ratio of 0.5 1.0 did not differ between cisatracurium and rocuronium, and was significantly shortened by the administration of neostigmine. We conclude that a neostigmine dose of 40 MUg.kg(-1) was the most effective at reducing recovery time after neuromuscular blockade. PMID- 26874259 TI - Energy biotechnology in the CRISPR-Cas9 era. AB - The production of bioenergy from plant biomass previously relied on using microorganisms that rapidly and efficiently convert simple sugars into fuels and chemicals. However, to exploit the far more abundant carbon fixed in plant cell walls, future industrial production hosts will need to be engineered to leverage the most efficient biochemical pathways and most robust traits that can be found in nature. The CRISPR-Cas9 genome editing technology now enables writing the genome at will, which will allow biotechnology to become an 'information science.' This review covers recent advances in using CRISPR-Cas9 to engineer the genomes of a wide variety of organisms that could be use in the industrial production of biofuels and renewable chemicals. PMID- 26874260 TI - Technical issues in the large-scale hydrothermal liquefaction of microalgal biomass to biocrude. AB - Much of the current knowledge on the hydrothermic liquefaction of biomass to biocrude is on the basis of laboratory benchtop findings, and the step up to industrial scale reactors will require a range of information that is currently either unavailable or insufficient. This work highlights a number of these issues such as the heat of reaction, process heat recovery, optimal reaction time and waste product treatment. Effects of these knowledge gaps on the reactor design, process economics, and impacts on the environment are discussed. Although technologies do exist to deal with some of these issues, their applications are often limited by economic considerations and further studies are required. PMID- 26874261 TI - Synthetic bugs on the loose: containment options for deeply engineered (micro)organisms. AB - Synthetic Biology (SynBio) has brought up again questions on the environmental fate of microorganisms carrying genetic modifications. The growing capacity of editing genomes for deployment of man-made programs opens unprecedented biotechnological opportunities. But the same exacerbate concerns regarding fortuitous or deliberate releases to the natural medium. Most approaches to tackle these worries involve endowing SynBio agents with containment devices for halting horizontal gene transfer and survival of the live agents only at given times and places. Genetic circuits and trophic restraint schemes have been proposed to this end in the pursuit of complete containment. The most promising include adoption of alternative genetic codes and/or dependency on xenobiotic amino acids and nucleotides. But the field has to still overcome serious bottlenecks. PMID- 26874262 TI - Biofuels from food processing wastes. AB - Food processing industry generates substantial high organic wastes along with high energy uses. The recovery of food processing wastes as renewable energy sources represents a sustainable option for the substitution of fossil energy, contributing to the transition of food sector towards a low-carbon economy. This article reviews the latest research progress on biofuel production using food processing wastes. While extensive work on laboratory and pilot-scale biosystems for energy production has been reported, this work presents a review of advances in metabolic pathways, key technical issues and bioengineering outcomes in biofuel production from food processing wastes. Research challenges and further prospects associated with the knowledge advances and technology development of biofuel production are discussed. PMID- 26874263 TI - Into new territory: improved microbial synthesis through engineering of the essential metabolic network. AB - Advances in synthetic biology and metabolic engineering offer the promise of next generation bioprocesses to produce numerous products including specialty and bulk chemicals and even biofuels sustainably from renewable feedstocks. A primary challenge is the optimization of product flux, within a much larger and complex metabolic network. While simple gene deletion methods can be used in the case of non-essential byproduct pathways, more sophisticated approaches are required when competitive fluxes are essential to host cellular functions. Engineering essential metabolic networks has been traditionally off-limits to metabolic engineers. Newer approaches to be reviewed include the rebalancing or rewiring of the metabolic network by tuning the levels of essential enzymes and the use of dynamic metabolic control strategies to conditionally reduce essential competitive fluxes. PMID- 26874264 TI - Scaling up of renewable chemicals. AB - The transition of promising technologies for production of renewable chemicals from a laboratory scale to commercial scale is often difficult and expensive. As a result the timeframe estimated for commercialization is typically underestimated resulting in much slower penetration of these promising new methods and products into the chemical industries. The theme of 'sugar is the next oil' connects biological, chemical, and thermochemical conversions of renewable feedstocks to products that are drop-in replacements for petroleum derived chemicals or are new to market chemicals/materials. The latter typically offer a functionality advantage and can command higher prices that result in less severe scale-up challenges. However, for drop-in replacements, price is of paramount importance and competitive capital and operating expenditures are a prerequisite for success. Hence, scale-up of relevant technologies must be interfaced with effective and efficient management of both cell and steel factories. Details involved in all aspects of manufacturing, such as utilities, sterility, product recovery and purification, regulatory requirements, and emissions must be managed successfully. PMID- 26874265 TI - Development and Assessment of a Questionnaire to Study Protection, Promotion, and Support of Breastfeeding. AB - OBJECTIVE: To develop an instrument to measure variables that influence health care professionals' behavior with regard to the protection, promotion, and support of breastfeeding, especially one that related to the Baby-Friendly Hospital Initiative (BFHI), and to conduct a psychometric assessment. DESIGN: Cross-sectional study. SETTING: Two public health departments in eastern Spain. PARTICIPANTS: A convenience sample of 201 maternity and primary care professionals. METHODS: The Questionnaire of Professional Breastfeeding Support of the Healthcare Quality Management Program of the Spanish Region of Murcia (QPBS-EMCA) was developed using the theory of reasoned action as a conceptual framework and the Global Criteria for evaluating implementation of the BFHI. It comprises 4 scales on beliefs, attitudes, subjective norms, and behavioral intention. The development process included item assessment and selection based on expert judgment and statistical criteria. The QPBS-EMCA scales were assessed for reliability and validity, including internal consistency, principal components factor analysis, criterion-related validity, and comparison of contrasted groups. RESULTS: The Beliefs, Attitudes, and Subjective Norms Scales were multidimensional, whereas the Behavioral Intention Scale was unidimensional. Cronbach's alpha coefficients ranged from .65 to .81. Total scores for the Beliefs, Attitudes, and Subjective Norms Scales predicted scores for the Behavioral Intention Scale. Scores for the different QPBS-EMCA scales were related to professionals' previous breastfeeding training, interest in new training, and appraisal of breastfeeding policy in the workplace. CONCLUSION: The psychometric characteristics of the QPBS-EMCA render it suitable for evaluation of professionals' beliefs, attitudes, subjective norms, and behavioral intention in relation to breastfeeding and could be useful in health care facilities implementing quality improvement processes based on the BFHI. PMID- 26874266 TI - Validity of Measurement in Nursing or Any Other Science. PMID- 26874268 TI - GH response to intravenous clonidine challenge correlates with history of childhood trauma in personality disorder. AB - BACKGROUND: Childhood trauma is a risk factor for personality disorder. We have previously shown that childhood trauma is associated with increased central corticotrophin-releasing hormone concentration in adults with personality disorder. In the brain, the release of corticotrophin-releasing hormone can be stimulated by noradrenergic neuronal activity, raising the possibility that childhood trauma may affect the hypothalamic-pituitary adrenal (HPA) axis by altering brain noradrenergic function. In this study, we sought to test the hypothesis that childhood trauma is associated with blunted growth hormone response to the alpha-2 adrenergic autoreceptor agonist clonidine. METHODS: All subjects provided written informed consent. Twenty personality disordered and twenty healthy controls (without personality disorder or Axis I psychopathology) underwent challenge with clonidine, while plasma Growth Hormone (GH) concentration was monitored by intravenous catheter. On a different study session, subjects completed the Childhood Trauma Questionnaire and underwent diagnostic interviews. RESULTS: Contrary to our a priori hypothesis, childhood trauma was associated with enhanced GH response to clonidine. This positive relationship was present in the group of 40 subjects and in the subgroup 20 personality disordered subjects, but was not detected in the healthy control subjects when analyzed separately. The presence of personality disorder was unrelated to the magnitude of GH response. DISCUSSION: Childhood trauma is positively correlated with GH response to clonidine challenge in adults with personality disorder. Enhanced rather that blunted GH response differentiates childhood trauma from previously identified negative predictors of GH response, such as anxiety or mood disorder. PMID- 26874267 TI - Longitudinal Course of Risk for Parental Postadoption Depression. AB - OBJECTIVE: To determine whether the Postpartum Depression Predictors Inventory Revised (PDPI-R) could be used to reveal distinct classes of adoptive parents across time. DESIGN: Longitudinal data were collected via online surveys at 4 to 6 weeks preplacement, 4 to 6 weeks postplacement, and 5 to 6 months postplacement. SETTING: Participants were primarily clients of the largest adoption agency in the United States. PARTICIPANTS: Participants included 127 adoptive parents (68 mothers and 59 fathers). METHODS: We applied a latent class growth analysis to the PDPI-R and conducted mixed effects modeling of class, time, and class * time interaction for the following categories of explanatory variables: parental expectations, interpersonal variables, psychological symptoms, and life orientation. RESULTS: Four latent trajectory classes were found. Class 1 (55% of sample) showed a stably low level of PDPI-R scores over time. Class 2 (32%) reported mean scores below the cut-off points at all three time points. Class 3 (8%) started with scores at an intermediate level that increased after postplacement but decreased at 5 to 6 months postplacement. Class 4 (5%) had high mean scores at all three time points. Significant main effects were found for almost all explanatory variables for class and for several variables for time. Significant interactions between class and time were found for expectations about the child and amounts of love and ambivalence in parent's intimate relationship. CONCLUSION: Findings may help nurses be alert to trajectories of risk for postadoption depression. Additional factors not included in the PDPI-R may be needed to determine risk for postadoption depression in adoptive parents. PMID- 26874269 TI - Approach bias modification in inpatient psychiatric smokers. AB - Drug-related automatic approach tendencies contribute to the development and maintenance of addictive behavior. The present study investigated whether a nicotine-related approach bias can be modified in smokers undergoing inpatient psychiatric treatment by using a novel training variant of the nicotine Approach Avoidance-Task (AAT). Additionally, we assessed whether the AAT-training would affect smoking behavior. Inpatient smokers were randomly assigned to either an AAT-training or a sham-training condition. In the AAT-training condition, smokers were indirectly instructed to make avoidance movements in response to nicotine related pictures and to make approach movements in response to tooth-cleaning pictures. In the sham-training condition, no contingency between picture content und arm movements existed. Trainings were administered in four sessions, accompanied by a brief smoking-cessation intervention. Smoking-related self report measures and automatic approach biases toward smoking cues were measured before and after training. Three months after training, daily nicotine consumption was obtained. A total of 205 participants were recruited, and data from 139 participants were considered in the final analysis. Prior to the trainings, smokers in both conditions exhibited a stronger approach bias for nicotine-related pictures than for tooth-cleaning pictures. After both trainings, this difference was no longer evident. Although reduced smoking behavior at posttest was observed after both trainings, only the AAT-training led to a larger reduction of nicotine consumption at a three-month follow-up. Our preliminary data partially support the conclusion that the AAT might be a feasible tool to reduce smoking in the long-term in psychiatric patients, albeit its effect on other smoking-related measures remains to be explored. PMID- 26874270 TI - Dual-targeting superparamagnetic iron oxide nanoprobes with high and low target density for brain glioma imaging. AB - A major limit of superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic resonance (MR) imaging nanoprobe in clinical applications is that the SPIONs are unable to reach sufficient concentrations at the tumor site by passive targeting to produce an obvious contrast effect for tumor imaging. Single targeting SPIONs systems have been applied to improve the contrast effect. However, they still suffer from a lack of efficiency and specificity of the SPIONs to tumors. Herein, we developed folic acid (FA) and cyclic Arg-Gly-Asp-D Tyr-Lys (c(RGDyK)) dual-targeting nanoprobes based on Cy5.5 labeled Fe3O4 nanoparticles (NPs). The synergistic targeting ability of the dual-targeting Fe3O4 NPs and the effect of the dual-target density on targeting specificity were investigated in brain glioma-bearing mice. In vivo T2-weighted MR imaging of brain glioma-bearing mice and ex vivo near-infrared imaging of brains harboring gliomas suggested that the combination of dual-target increased the uptake of NPs by glioma, consequently, enhanced the contrast effect. Moreover, it was revealed that the density of dual-target plays an important role in targeting specificity. PMID- 26874271 TI - Aqueous extract from seeds of Silybum marianum L. as a green material for preparation of the Cu/Fe3O4 nanoparticles: A magnetically recoverable and reusable catalyst for the reduction of nitroarenes. AB - In this paper, we report the green synthesis of the Cu/Fe3O4 nanoparticles using Silybum marianum L. seeds extract and their application as magnetically separable nanocatalyst for the reduction of nitroarenes. Our method is clean, nontoxic and environment friendly. The synthesized nanocatalyst is characterized by XRD, TEM, EDS and UV-visible techniques. UV-visible spectroscopy is used to monitor the kinetics of the Cu/Fe3O4 nanoparticles formation. The results from Fourier transform infrared spectroscopy showed that the C=O and C-O groups in the plant seeds extract played a critical role in capping the nanoparticles. The expected reaction mechanism in the formation of nanoparticles is also reported. The catalyst is recoverable by magnetic decantation and could be reused several times without significant loss in catalytic activity. PMID- 26874272 TI - Assembly of functional gold nanoparticle on silica microsphere. AB - We demonstrate a controlled synthesis of silica microsphere with the surface decorated functional gold nanoparticles. Surface of silica microsphere was modified by 3-aminopropypltriethoxysilane and 3-aminopropyldimethylethoxysilane to generate a positive electric field, by which the gold nanoparticles with the negative charges (unconjugated, thiolated polyethylene glycol functionalized with the traceable packing density and conformation) were able to be attracted to the silica microsphere. Results show that both the molecular conjugation on gold nanoparticle and the uniformity in the amino-silanization of silica microsphere influenced the loading and the homogeneity of gold nanoparticles on silica microsphere. The 3-aminopropyldimethylethoxysilane-functionalized silica microsphere provided an uniform field to attract gold nanoparticles. Increasing the ethanol content in aminosilane solution significantly improved the homogeneity and the loading of gold nanoparticles on the surface of silica microsphere. For the gold nanoparticle, increasing the molecular mass of polyethylene glycol yielded a greater homogeneity but a lower loading on silica microsphere. Bovine serum albumin induced the desorption of gold nanoparticles from silica microsphere, where the extent of desorption was suppressed by the presence of high-molecular mass polyethylene glycol on gold nanoparticles. This work provides the fundamental understanding for the synthesis of gold nanoparticle-silica microsphere constructs useful to the applications in chemo radioactive therapeutics. PMID- 26874273 TI - Nano-diamond particles functionalized with single/double-arm amide-thiourea ligands for adsorption of metal ions. AB - Separation efficiency of solid-phase extractant is greatly subjected to the spatial configurations of functional ligands attached to the matrix, which has not been studied efficiently till now. In order to further understand the relationship between spatial configurations of the attached functional ligand and the adsorption ability of the extractant, two novel molecules (single-armed ligand, SA and double-armed ligand, DA) with identical coordination unit (amide thiourea) but different spatial configurations (single/double arms) were designed and synthesized. The corresponding extractants, ND-SA and ND-DA were obtained by modification of nanodiamond (ND) with SA and DA and both the extractants displayed good chemical and thermal stabilities. The batch adsorption experiments showed that ND-SA and ND-DA possess large adsorption capacities (~200 mg g(-1)), very fast adsorption kinetics (reaching equilibrium within 2 min) and excellent selectivities (up to 82% and 72%, respectively) for uranium. The study of the possible mechanism indicated that ND-DA tends to utilize its tweezer-like double arms to "clamp" metal ions and the stronger chelate interaction could to some extent weaken the coordination selectivity of attached DA ligand. In contrast, single-armed adsorbent ND-SA unexpectedly exhibited better adsorption selectivity for uranium than ND-DA owing to its more flexible spatial configuration and moderate complexing ability. PMID- 26874274 TI - Influence of internal composition on physicochemical properties of alginate aqueous-core capsules. AB - HYPOTHESIS: To enhance physicochemical properties of alginate aqueous-core capsules, conventional strategies were focused in literature on designing composite and coated capsules. In the present study, own effect of liquid-core composition on mechanical and release properties was investigated. EXPERIMENTS: Capsules were prepared by dripping a CaCl2 solution into an alginate gelling solution. Viscosity of CaCl2 solution was adjusted by adding cationic, anionic and non-ionic naturally derived polymers, respectively chitosan, xanthan gum and guar gum. In parallel, uniform alginate hydrogels were prepared by different methods (pouring, in situ forming and mixing). Mechanical stability of capsules and plane hydrogels were respectively evaluated by compression experiments and small amplitude oscillatory shear rheology and then correlated. Capsules permeability was evaluated by monitoring diffusion of encapsulated cochineal dye, riboflavin and BSA. The core-shell interactions were investigated by ATR-FTIR. FINDINGS: Results showed that inner polymer had an impact on membrane stability and could act as an internal coating or provide mechanical reinforcement. Mechanical properties of alginate capsules were in a good agreement with rheological behavior of plane hydrogels. Release behavior of the entrapped molecules changed considerably. This study demonstrated the importance of aqueous core composition, and gave new insights for possible adjusting of microcapsules physicochemical properties by modulating core-shell interactions. PMID- 26874275 TI - The safety of subcutaneously administered depot medroxyprogesterone acetate (104mg/0.65mL): A systematic review. AB - CONTEXT: Depot medroxyprogesterone acetate (DMPA), a progestogen-only contraceptive injectable, has traditionally been formulated as a crystalline suspension delivered intramuscularly (IM) at a dose of 150mg/1.0mL. A new, lower dose formulation of DMPA (104mg/0.65mL) has been developed for subcutaneous administration (SC). Given its increasing global availability and public health relevance, DMPA-SC was prioritized for inclusion as a new method referenced in the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use (MEC), 5th Edition. OBJECTIVE: This systematic review evaluated the published peer-reviewed literature regarding the safety of DMPA-SC among women with various characteristics or medical conditions. Results of this review informed the decision-making of a WHO Guideline Development Group in order to include recommendations on contraceptive eligibility within the revised MEC. METHODS: We searched PubMed and Cochrane Library databases to identify all relevant evidence published in peer-reviewed journals regarding the safety of DMPA-SC when used by women of reproductive age, particularly those with select characteristics or conditions specified in the MEC, from inception through June 2015. The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. RESULTS: Fourteen studies met criteria for inclusion. Ten reported results relevant to DMPA users of varying age or with obesity, endometriosis or HIV; four compared the safety of DMPA-SC and DMPA-IM when used by general populations of healthy women. A randomized trial evaluating changes in bone mineral density among adult DMPA-SC and DMPA-IM users demonstrated no differences at 2years of follow-up. Limited evidence reported no consistent differences in weight change or bleeding patterns according to age; however, adolescents (<18years) were not included in any studies. Similar contraceptive efficacy, weight change, bleeding patterns and occurrence of other adverse effects among obese and nonobese DMPA-SC users were observed. Women with endometriosis using DMPA-SC over 6months had minimal decreases in bone mineral density, weight gain, few serious adverse events and experienced improved pain symptoms. Women living with HIV tolerated injection of DMPA-SC with rare complications. DMPA-SC and DMPA-IM also show therapeutic equivalence and similar effects on weight gain, changes in bleeding patterns and reports of other adverse effects when these different delivery systems were used by general populations of women. CONCLUSION: Evidence for use of DMPA-SC by women with select conditions and characteristics including age, obesity, endometriosis or HIV demonstrates that this method can generally be used safely in these contexts. Further, DMPA-SC and DMPA-IM appear to be therapeutically equivalent with similar safety profiles when used by healthy women. PMID- 26874276 TI - Reduction of PCN biosynthesis by NO in Pseudomonas aeruginosa. AB - Pyocyanin (PCN), a virulence factor synthesized by Pseudomonas aeruginosa, plays an important role during clinical infections. There is no study of the effect of nitric oxide (NO) on PCN biosynthesis. Here, the effect of NO on PCN levels in Pseudomonas aeruginosa strain PAO1, a common reference strain, was tested. The results showed that the NO donor sodium nitroprusside (SNP) can significantly reduce PCN levels (82.5% reduction at 60MUM SNP). Furthermore, the effect of endogenous NO on PCN was tested by constructing PAO1 nor (NO reductase gene) knockout mutants. Compared to the wild-type strain, the Deltanor strain had a lower PCN (86% reduction in Deltanor). To examine whether the results were universal with other P. aeruginosa strains, we collected 4 clinical strains from a hospital, tested their PCN levels after SNP treatment, and obtained similar results, i.e., PCN biosynthesis was inhibited by NO. These results suggest that NO treatment may be a new strategy to inhibit PCN biosynthesis and could provide novel insights into eliminating P. aeruginosa virulence as a clinical goal. PMID- 26874277 TI - Prolyl isomerase Pin1 regulates doxorubicin-inducible P-glycoprotein level by reducing Foxo3 stability. AB - It has been known that the phosphoSer/Thr-Pro-specific peptidyl prolyl cis/trans isomerase Pin1 regulates a variety of intracellular signaling pathways, including the response to the genotoxic drug doxorubicin. Pin1 binds phosphorylated p53 and stabilizes p53 to cause cell cycle arrest and apoptosis quickly in response to doxorubicin. Here we show another mechanism of Pin1 to maintain cell sensitivity to genotoxic stress, irrespective of whether p53 is present or not. In response to the genotoxic drug, Pin1 binds and decreases levels of the phosphorylated Foxo3, the positive transcription factor of P-glycoprotein (P-gp) gene. Through this mechanism of action, Pin1 decreases the level of P-gp and signals the cell to pump the genotoxic drugs out. This shows that Pin1 is implemented in maintaining the susceptibility to the genotoxic drugs by controlling P-gp level as well as p53-dependent apoptosis and cell cycle signaling pathways. PMID- 26874278 TI - TGF-beta1 activates the canonical NF-kappaB signaling to promote cell survival and proliferation in dystrophic muscle fibroblasts in vitro. AB - Activated fibroblasts continue to proliferate at injury sites, leading to progressive muscular fibrosis in Duchenne muscular dystrophy (DMD). TGF-beta1 is a dominant profibrotic mediator thought to play a critical role in muscle fibrosis; however, the implicated mechanisms are not fully understood. Here we showed that TGF-beta1 increased the resistance to apoptosis and stimulated cell cycle progression in dystrophic muscle fibroblasts under serum deprivation conditions in vitro. TGF-beta1 treatment activated the canonical NF-kappaB pathway; and we found that pharmacological inhibition of IKKbeta with IMD-0354 and RelA gene knockdown with siRNA attenuated these effects of TGF-beta1 on dystrophic muscle fibroblasts. Collectively, our data suggest that TGF-beta1 prevents apoptosis and cell cycle arrest in dystrophic muscle fibroblasts through the canonical NF-kappaB signaling pathway. PMID- 26874280 TI - A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging. AB - The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple beta-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-betaCD (DOTA-Gd) specifically bond to alphavbeta3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to alphavbeta3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID- 26874282 TI - H2O2-triggered bubble generating antioxidant polymeric nanoparticles as ischemia/reperfusion targeted nanotheranostics. AB - Overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) leads to oxidative stress, causing inflammation and cellular damages and death. H2O2 is one of the most stable and abundant ROS and H2O2-mediated oxidative stress is considered as a key mediator of cellular and tissue damages during ischemia/reperfusion (I/R) injury. Therefore, H2O2 could hold tremendous potential as a diagnostic biomarker and therapeutic target for oxidative stress associated inflammatory conditions such as I/R injury. Here, we report a novel nanotheranostic agent that can express ultrasound imaging and simultaneous therapeutic effects for hepatic I/R treatment, which is based on H2O2-triggered CO2-generating antioxidant poly(vanillin oxalate) (PVO). PVO nanoparticles generate CO2 through H2O2-triggered oxidation of peroxalate esters and release vanillin, which exerts antioxidant and anti-inflammatory activities. PVO nanoparticles intravenously administrated remarkably enhanced the ultrasound signal in the site of hepatic I/R injury and also effectively suppressed the liver damages by inhibiting inflammation and apoptosis. To our best understanding, H2O2-responsive PVO is the first platform which generates bubbles to serve as ultrasound contrast agents and also exerts therapeutic activities. We therefore anticipate that H2O2-triggered bubble-generating antioxidant PVO nanoparticles have great potential for ultrasound imaging and therapy of H2O2 associated diseases. PMID- 26874281 TI - Transdifferentiation of human endothelial progenitors into smooth muscle cells. AB - Access to smooth muscle cells (SMC) would create opportunities for tissue engineering, drug testing, and disease modeling. Herein we report the direct conversion of human endothelial progenitor cells (EPC) to induced smooth muscle cells (iSMC) by induced expression of MYOCD. The EPC undergo a cytoskeletal rearrangement resembling that of mesenchymal cells within 3 days post initiation of MYOCD expression. By day 7, the reprogrammed cells show upregulation of smooth muscle markers ACTA2, MYH11, and TAGLN by qRT-PCR and ACTA2 and MYH11 expression by immunofluorescence. By two weeks, they resemble umbilical artery SMC in microarray gene expression analysis. The iSMC, in contrast to EPC control, show calcium transients in response to phenylephrine stimulation and a contractility an order of magnitude higher than that of EPC as determined by traction force microscopy. Tissue-engineered blood vessels constructed using iSMC show functionality with respect to flow- and drug-mediated vasodilation and vasoconstriction. PMID- 26874284 TI - Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging. AB - Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor. PMID- 26874283 TI - Synthesis and characterization of anti-bacterial and anti-fungal citrate-based mussel-inspired bioadhesives. AB - Bacterial and fungal infections in the use of surgical devices and medical implants remain a major concern. Traditional bioadhesives fail to incorporate anti-microbial properties, necessitating additional anti-microbial drug injection. Herein, by the introduction of the clinically used and inexpensive anti-fungal agent, 10-undecylenic acid (UA), into our recently developed injectable citrate-based mussel-inspired bioadhesives (iCMBAs), a new family of anti-bacterial and anti-fungal iCMBAs (AbAf iCs) was developed. AbAf iCs not only showed strong wet tissue adhesion strength, but also exhibited excellent in vitro cyto-compatibility, fast degradation, and strong initial and considerable long term anti-bacterial and anti-fungal ability. For the first time, the biocompatibility and anti-microbial ability of sodium metaperiodate (PI), an oxidant used as a cross-linking initiator in the AbAf iCs system, was also thoroughly investigated. Our results suggest that the PI-based bioadhesives showed better anti-microbial properties compared to the unstable silver-based bioadhesive materials. In conclusion, AbAf iCs family can serve as excellent anti bacterial and anti-fungal bioadhesive candidates for tissue/wound closure, wound dressing, and bone regeneration, especially when bacterial or fungal infections are a major concern. PMID- 26874285 TI - Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot. AB - Here, we describe combinational chemotherapy via intratumoral injection of doxorubicin (Dox) and 5-fluorouracil (Fu) to enhance the efficacy and reduce the toxicity of systemically administered Fu and Dox in cancer patients. As the key concept in this work, mixture formulations of Dox-loaded microcapsules (Dox-M) and Fu-loaded Pluronic((r)) hydrogels (Fu-HP) or Fu-loaded diblock copolymer hydrogels (Fu-HC) have been employed as drug depots. The in vitro and in vivo drug depot was designed as a formulation of Dox-M dispersed inside an outer shell of Fu-HP or Fu-HC after injection. The Dox-M/Fu-HP and Dox-M/Fu-HC formulations are free flowing at room temperature, indicating injectability, and formed a structural gelatinous depot in vitro and in vivo at body temperature. The Fu-HP, Fu-HC, Dox-M/Fu-HP, Dox-M/Fu-HC, and Dox-M formulations were easily injected into tumor centers in mice using a needle. Dox-M/Fu-HC produced more significant inhibitory effects against tumor growth than that by Dox-M/Fu-HP, while Fu-HP, Fu HC and Dox-M had the weakest inhibitory effects of the tested treatments. The in vivo study of Dox and Fu biodistribution showed that high Dox and Fu concentrations were maintained in the target tumor only, while distribution to normal tissues was not observed, indicating that Dox and Fu concentrations below their toxic plasma concentrations should not cause significant systemic toxicity. The Dox-M/Fu-HP and Dox-M/Fu-HC drug depots described in this work showed excellent performance as chemotherapeutic delivery systems. The results reported here indicate that intratumoral injection using combination chemotherapy with Dox M/Fu-HP or Dox-M/Fu-HC could be of translational research by enhancing the synergistic inhibitory effects of Dox and Fu on tumor growth, while reducing their systemic toxicity in cancer patients. PMID- 26874286 TI - Optimization and evaluation of a method to detect adenoviruses in river water. AB - Adenoviruses are often implicated in recreational water disease outbreaks but existing methods for their detection perform poorly within these matrices. In this study, small volume (100mL) concentration was used to identify processes that promoted recovery of adenovirus from river water. Several alternative secondary concentration techniques were investigated and compared to the baseline method consisting of primary concentration via filtration, followed by celite mediated secondary concentration. The alternative secondary concentrations included multiple filter elutions, soaking the filter for 15 min prior to elution and concentration using pre-treated celite (river water, 1.5% and 3% milk) instead of a filter. Modifications of the viral nucleic acid extraction technique were also evaluated. Concentration using pre-treated celite and a modified extraction technique (10 min boil and a 1h ProK incubation at 37 degrees C) recovered significantly higher levels of adenovirus (P=0.001) than other methods tested. This optimized method increased recovery of spiked adenovirus (57 +/- 27%) compared to baseline method performance (4 +/- 3%) indicating that use of pre-treated celite as opposed to filtration significantly improves recovery. Application of the optimized concentration method to larger volume (1L) of river water resulted in similar recoveries (42 +/- 19%) underlying the utility of this method to detect adenovirus from environmental samples. PMID- 26874287 TI - Development and validation of quantitative PCR for detection of Terrapene herpesvirus 1 utilizing free-ranging eastern box turtles (Terrapene carolina carolina). AB - Diseases that affect the upper respiratory tract (URT) in chelonians have been well described as a significant contributor of morbidity and mortality. Specifically, herpesviruses are common pathogens in captive chelonians worldwide, but their importance on free-ranging populations is less well known. Historical methods for the diagnosis of herpesvirus infections include virus isolation and conventional PCR. Real-time PCR has become an essential tool for detection and quantitation of many pathogens, but has not yet been developed for herpesviruses in box turtles. Two quantitative real-time TaqMan PCR assays, TerHV58 and TerHV64, were developed targeting the DNA polymerase gene of Terrapene herpesvirus 1 (TerHV1). The assay detected a viral DNA segment cloned within a plasmid with 10-fold serial dilutions from 1.04 * 10(7) to 1.04 * 10(1) viral copies per reaction. Even though both primers had acceptable levels of efficiency and variation, TerHV58 was utilized to test clinical samples based on less variation and increased efficiency. This assay detected as few as 10 viral copies per reaction and should be utilized in free-ranging and captive box turtles to aid in the characterization of the epidemiology of this disease. PMID- 26874288 TI - Statistical shape analysis using 3D Poisson equation--A quantitatively validated approach. AB - Statistical shape analysis has been an important area of research with applications in biology, anatomy, neuroscience, agriculture, paleontology, etc. Unfortunately, the proposed methods are rarely quantitatively evaluated, and as shown in recent studies, when they are evaluated, significant discrepancies exist in their outputs. In this work, we concentrate on the problem of finding the consistent location of deformation between two population of shapes. We propose a new shape analysis algorithm along with a framework to perform a quantitative evaluation of its performance. Specifically, the algorithm constructs a Signed Poisson Map (SPoM) by solving two Poisson equations on the volumetric shapes of arbitrary topology, and statistical analysis is then carried out on the SPoMs. The method is quantitatively evaluated on synthetic shapes and applied on real shape data sets in brain structures. PMID- 26874289 TI - Active membrane cholesterol as a physiological effector. AB - Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily. PMID- 26874291 TI - Differential treatment response trajectories in individuals with subclinical and clinical PTSD. AB - Subclinical presentations of posttraumatic stress disorder (PTSD), wherein patients are one or two symptom criteria short of the full disorder, are prevalent and associated with levels of distress and impaired functioning approximating that of full PTSD. Nonetheless, research examining treatment efficacy for this group is in the nascent stage. The purpose of the present study was to examine whether the subclinical PTSD group would: (1) show a greater reduction in PTSD symptoms at pre and post treatment in response to an exposure based treatment and (2) show a greater rate of change over the course of treatment, when compared to the full criteria PTSD group. We also examined whether differences would emerge when examining PTSD symptom clusters. Consistent with predictions, the subclinical PTSD group demonstrated a greater reduction in PTSD symptoms at post-treatment (29%) than those with a PTSD diagnosis (14%). Further, the groups had different treatment trajectories, with the subclinical PTSD group showing a marginally greater rate of change during the course of treatment. Findings also varied by symptom cluster with the subclinical group showing a greater rate of change in the intrusions, hypervigilance, and avoidance symptom clusters. There was not a significant between group difference in the numbing symptom cluster. This study provides preliminary evidence that treating PTSD symptoms at the subclinical level may result in a larger, and more rapid symptom reduction, and thus has implications supporting treatment earlier in the developmental trajectory of the disorder. PMID- 26874292 TI - The shared and specific relationships between exposure to potentially traumatic events and transdiagnostic dimensions of psychopathology. AB - The experience of traumatic events has been linked to the development of psychopathology. Changing perspectives on psychopathology have resulted in the hypothesis that broad dimensional constructs account for the majority of variance across putatively distinct disorders. As such, traumatic events may be associated with several disorders due to their relationship with these broad dimensions rather than any direct disorder-specific relationship. The current study used data from 8871 Australians to test this hypothesis. Two broad dimensions accounted for the majority of relationships between traumatic events and mental and substance use disorders. Direct relationships remained between post-traumatic stress disorder and six categories of traumatic events in the total population and between drug dependence and accidents/disasters for males only. These results have strong implications for how psychopathology is conceptualized and offer some evidence that traumatic events are associated with an increased likelihood of experiencing psychopathology in general. PMID- 26874293 TI - Risk appraisal of passing zones on two-lane rural highways and policy applications. AB - Passing on two-lane rural highways is associated with risks of head-on collision resulting from unsafe completion of passing maneuvers in the opposite traffic lane. In this paper, we explore the use of time-to-collision (TTC) as a surrogate safety measure of the risk associated with passing maneuvers. Logistic regression models to predict the probability to end the passing maneuver with TTC less than 2 or 3s-threshold were developed with the time-gap from initiation of the maneuver to arrival of the opposite vehicle (effective accepted gap), and the passing duration as explanatory variables. The data used for model estimation was collected using stationary tripod-mounted camcorders at 19 passing zones in Uganda. Results showed that passing maneuvers completed with TTC less than 3s are unsafe and often involved sudden speed reduction, flashing headlights, and lateral shift to shoulders. Model sensitivity analysis was conducted for observed passing durations involving passenger cars or short trucks (2-3 axles), and long trucks (4-7 axles) as the passed vehicles for 3s TTC-threshold. Three risk levels were proposed based on the probability to complete passing maneuvers with TTC less than 3s for a range of opposite direction traffic volumes. Applications of the results for safety improvements of two-lane rural highways are also discussed. PMID- 26874294 TI - Structural and transcriptional characterization of a novel member of the soybean urease gene family. AB - In plants, ureases have been related to urea degradation, to defense against pathogenic fungi and phytophagous insects, and to the soybean-Bradyrhizobium japonicum symbiosis. Two urease isoforms have been described for soybean: the embryo-specific, encoded by Eu1 gene, and the ubiquitous urease, encoded by Eu4. A third urease-encoding locus exists in the completed soybean genome. The gene was designated Eu5 and the putative product of its ORF as SBU-III. Phylogenetic analysis shows that 41 plant, moss and algal ureases have diverged from a common ancestor protein, but ureases from monocots, eudicots and ancient species have evolved independently. Genomes of ancient organisms present a single urease encoding gene and urease-encoding gene duplication has occurred independently along the evolution of some eudicot species. SBU-III has a shorter amino acid sequence, since many gaps are found when compared to other sequences. A mutation in a highly conserved amino acid residue suggests absence of ureolytic activity, but the overall protein architecture remains very similar to the other ureases. The expression profile of urease-encoding genes in different organs and developmental stages was determined by RT-qPCR. Eu5 transcripts were detected in seeds one day after dormancy break, roots of young plants and embryos of developing seeds. Eu1 and Eu4 transcripts were found in all analyzed organs, but Eu4 expression was more prominent in seeds one day after dormancy break whereas Eu1 predominated in developing seeds. The evidence suggests that SBU-III may not be involved in nitrogen availability to plants, but it could be involved in other biological role(s). PMID- 26874295 TI - Molecular and biochemical characterization of rice pectin methylesterase inhibitors (OsPMEIs). AB - Cell wall modifications such as partial degradation and depolymerization by cell wall hydrolases are normal cellular processes and are required for the functionalities of different cell types. Pectin, one of the major cell wall polysaccharides, is predominantly found in primary cell walls and middle lamellae and is subjected to in muro modification, primarily by cell wall-localized pectin methylesterases (PMEs). Molecular biochemical studies have demonstrated that enzymatic activities of PMEs are governed by multiple pectin methylesterase inhibitors (PMEIs), which consequently control the pectin methylesterification status. Although a few studies in Arabidopsis have shown the importance of this PMEI-mediated regulation in the biophysical properties of cell walls, little is known about the molecular physiological functions of rice PMEIs. We found 49 members of the PMEI family in the rice genome. Analysis of their transcript levels by quantitative real-time PCR and meta expression analysis showed that they are regulated spatially and temporally, as well as in response to diverse stresses. Quantification of cell wall-bound methylesters indicated that the degree of pectin methylesterification is developmentally regulated; in particular, higher PMEI activities were detected in cell wall proteins prepared from young leaves. Furthermore, an activity assay demonstrated that two recombinant OsPMEI proteins (OsPMEI8 and 12) were able to inhibit the enzymatic activity of a commercial PME protein. Subcellular localization indicated that OsPMEI8 is targeted to the middle lamella and OsPMEI12 is localized in the plasma membrane and nucleus. Taken together, our findings provide the first molecular and biochemical evidence for functional characterization of PMEIs in rice growth and development. PMID- 26874296 TI - Relationship between potassium fertilization and nitrogen metabolism in the leaf subtending the cotton (Gossypium hirsutum L.) boll during the boll development stage. AB - The nitrogen (N) metabolism of the leaf subtending the cotton boll (LSCB) was studied with two cotton (Gossypium hirsutum L.) cultivars (Simian 3, low-K tolerant; Siza 3, low-K sensitive) under three levels of potassium (K) fertilization (K0: 0 g K2O plant(-1), K1: 4.5 K2O plant(-1) and K2: 9.0 g K2O plant(-1)). The results showed that total dry matter increased by 13.1-27.4% and 11.2-18.5% under K supply for Simian 3 and Siza 3. Boll biomass and boll weight also increased significantly in K1 and K2 treatments. Leaf K content, leaf N content and nitrate (NO3(-)) content increased with increasing K rates, and leaf N content or NO3(-) content had a significant positive correlation with leaf K content. Free amino acid content increased in the K0 treatment for both cultivars, due to increased protein degradation caused by higher protease and peptidase activities, resulting in lower protein content in the K0 treatment. The critical leaf K content for free amino acid and soluble protein content were 14 mg g(-1) and 15 mg g(-1) in Simian 3, and 17 mg g(-1) and 18 mg g(-1) in Siza 3, respectively. Nitrate reductase (NR), glutamic-oxaloace transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities increased in the K1 and K2 treatments for both cultivars, while glutamine synthetase (GS) and glutamate synthase (GOGAT) activities increased under K supply treatments only for Siza 3, and were not affected in Simian 3, indicating that this was the primary difference in nitrogen-metabolizing enzymes activities for the two cultivars with different sensitivity to low-K. PMID- 26874297 TI - Development and validation of a spontaneous preterm delivery predictor in asymptomatic women. AB - BACKGROUND: Preterm delivery remains the leading cause of perinatal mortality. Risk factors and biomarkers have traditionally failed to identify the majority of preterm deliveries. OBJECTIVE: To develop and validate a mass spectrometry-based serum test to predict spontaneous preterm delivery in asymptomatic pregnant women. STUDY DESIGN: A total of 5501 pregnant women were enrolled between 17(0/7) and 28(6/7) weeks gestational age in the prospective Proteomic Assessment of Preterm Risk study at 11 sites in the United States between 2011 and 2013. Maternal blood was collected at enrollment and outcomes collected following delivery. Maternal serum was processed by a proteomic workflow, and proteins were quantified by multiple reaction monitoring mass spectrometry. The discovery and verification process identified 2 serum proteins, insulin-like growth factor binding protein 4 (IBP4) and sex hormone-binding globulin (SHBG), as predictors of spontaneous preterm delivery. We evaluated a predictor using the log ratio of the measures of IBP4 and SHBG (IBP4/SHBG) in a clinical validation study to classify spontaneous preterm delivery cases (<37(0/7) weeks gestational age) in a nested case-control cohort different from subjects used in discovery and verification. Strict blinding and independent statistical analyses were employed. RESULTS: The predictor had an area under the receiver operating characteristic curve value of 0.75 and sensitivity and specificity of 0.75 and 0.74, respectively. The IBP4/SHBG predictor at this sensitivity and specificity had an odds ratio of 5.04 for spontaneous preterm delivery. Accuracy of the IBP4/SHBG predictor increased using earlier case-vs-control gestational age cutoffs (eg, <35(0/7) vs >=35(0/7) weeks gestational age). Importantly, higher-risk subjects defined by the IBP4/SHBG predictor score generally gave birth earlier than lower risk subjects. CONCLUSION: A serum-based molecular predictor identifies asymptomatic pregnant women at risk of spontaneous preterm delivery, which may provide utility in identifying women at risk at an early stage of pregnancy to allow for clinical intervention. This early detection would guide enhanced levels of care and accelerate development of clinical strategies to prevent preterm delivery. PMID- 26874298 TI - The impact of ambient operating room temperature on neonatal and maternal hypothermia and associated morbidities: a randomized controlled trial. AB - BACKGROUND: Neonatal hypothermia is common at the time of cesarean delivery and has been associated with a constellation of morbidities in addition to increased neonatal mortality. Additionally, maternal hypothermia is often uncomfortable for the surgical patient and has been associated with intraoperative and postoperative complications. Various methods to decrease the rates of neonatal and maternal hypothermia have been examined and found to have varying levels of success. OBJECTIVE: We sought to determine whether an increase in operating room temperature at cesarean delivery results in a decrease in the rate of neonatal hypothermia and associated morbidities. STUDY DESIGN: In this single-center randomized trial, operating room temperatures were adjusted weekly according to a cluster randomization schedule to either 20 degrees C (67 degrees F), which was the standard at our institution, or 23 degrees C (73 degrees F), which was the maximum temperature allowable per hospital policy. Neonatal hypothermia was defined as core body temperature <36.5 degrees C (97.7 degrees F) per World Health Organization criteria. The primary study outcome was neonatal hypothermia on arrival to the admitting nursery. Measures of neonatal morbidity potentially associated with hypothermia were examined. RESULTS: From February through July 2015, 791 women who underwent cesarean deliveries were enrolled, resulting in 410 infants in the 20 degrees C standard management group and 399 in the 23 degrees C study group. The rate of neonatal hypothermia on arrival to the admitting nursery was lower in the study group as compared to the standard management group: 35% vs 50%, P < .001. Moderate to severe hypothermia was infrequent when the operating room temperature was 23 degrees C (5%); in contrast such hypothermia occurred in 19% of the standard management group, P < .001. Additionally, neonatal temperature in the operating room immediately following delivery and stabilization was also higher in the study group, 37.1 +/- 0.6 degrees C vs 36.9 +/- 0.6 degrees C, P < .001. We found no difference in rates of intubation, ventilator use, hypoglycemia, metabolic acidemia, or intraventricular hemorrhage. Fever (temperature >38.0 degrees C or 100.4 degrees F) on arrival to the admitting unit was uncommon and did not differ between the study groups. Maternal temperature on arrival to the operating room was not different between the 2 groups, however by delivery it was significantly lower in the standard management group, 36.2 +/- 0.6 degrees C vs 36.4 +/- 0.6 degrees C, P < .001. This effect persisted, as maternal temperature on arrival to the postoperative care area was lower in the standard management group, 36.1 +/- 0.6 degrees C vs 36.2 +/- 0.6 degrees C, P < .001, and the rate of hypothermia was higher, 77% vs 69%, P = .008. CONCLUSION: A modest increase in operating room temperature at the time of cesarean reduces the rate of neonatal and maternal hypothermia. We did not detect a decrease in neonatal morbidity, but the power to detect a small change in these outcomes was limited. PMID- 26874299 TI - Universal cervical length screening: implementation and outcomes. AB - BACKGROUND: Transvaginal measurement of cervical length (CL) has been advocated as a screening tool to prevent preterm birth, but controversy remains regarding the overall utility of universal screening. OBJECTIVE: We aimed to evaluate the acceptability of a universal CL screening program. Additionally we evaluated risk factors associated with declining screening and subsequent delivery outcomes of women who accepted or declined screening. STUDY DESIGN: This was a retrospective cohort study of transvaginal CL screening at a single institution from July 1, 2011, through December 31, 2014. Institutional protocol recommended transvaginal CL measurement at the time of anatomic survey between 17-23 weeks in all women with singleton, viable pregnancies, without current or planned cerclage, with patients able to opt out. Patients with CL <=20 mm were considered to have clinically significant cervical shortening and were offered treatment. We assessed acceptance rate, risk factors for declining CL screening, and the trend of acceptance of CL screening over time. We also calculated the prevalence of CL <=25, <=20, and <=15 mm, and estimated the association between CL screening and spontaneous preterm birth. RESULTS: Of 12,740 women undergoing anatomic survey during the study period, 10,871 (85.3%; 95% confidence interval [CI], 84.7-85.9%) underwent CL screening. Of those, 215 (2.0%) had a CL <=25 mm and 131 (1.2%) had a CL <=20 mm. After the first 6 months of implementation, there was no change in rates of acceptance of CL screening over time (P for trend = .15). Women were more likely to decline CL screening if they were African American (adjusted odds ratio [aOR], 2.17; 95% CI, 1.93-2.44), obese (aOR, 1.18; 95% CI, 1.06-1.31), multiparous (aOR, 1.45; 95% CI, 1.29-1.64), age <35 years (aOR, 1.24; 95% CI, 1.08-1.43), or smokers (aOR, 1.42; 95% CI, 1.20-1.68). Rates of spontaneous preterm birth <28 weeks were higher in those who declined CL screening (aOR, 2.01; 95% CI, 1.33-3.02). CONCLUSION: Universal CL screening was implemented successfully with 85% of women screened. Overall incidence of short cervix was low and women with significant risk factors for preterm birth were more likely to decline screening. Patients who declined CL screening were more likely to be African American, obese, multiparous, age <35 years, and smokers. Rates of early, but not late, spontaneous preterm birth were significantly higher among women who did not undergo CL screening. PMID- 26874300 TI - Novel lean type 2 diabetic rat model using gestational low-protein programming. AB - BACKGROUND: Type 2 diabetes (T2D) in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development. OBJECTIVE: Our objective was to develop a lean T2D model using gestational low-protein (LP) programming. STUDY DESIGN: Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Standard diet was given to dams after delivery and to pups after weaning. Glucose tolerance test was done at 2, 4, and 6 months of age. Magnetic resonance imaging of body fat for females was done at 4 months. Rats were sacrificed at 4 and 8 months of age and their perigonadal, perirenal, inguinal, and brown fat were weighed and expressed relative to their body weight. Euglycemic-hyperinsulinemic clamp was done around 6 months of age. RESULTS: Male and female offspring exposed to a LP diet during gestation developed glucose intolerance and insulin resistance (IR). Further, glucose intolerance progressed with increasing age and occurred earlier and was more severe in females when compared to males. Euglycemic-hyperinsulinemic clamp showed whole body IR in both sexes, with females demonstrating increased IR compared to males. LP females showed a 4.5-fold increase in IR while males showed a 2.5-fold increase when compared to their respective controls. Data from magnetic resonance imaging on female offspring showed no difference in the subcutaneous, inguinal, and visceral fat content. We were able to validate this observation by sacrificing the rats at 4 and 8 months and measuring total body fat content. This showed no differences in body fat content between control and LP offspring in either males or females. Additionally, diabetic rats had a similar body mass index to that of the controls. CONCLUSION: LP gestational programming produces a progressively worsening T2D model in rats with a lean phenotype without obesity. PMID- 26874301 TI - A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later. AB - BACKGROUND: A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood. OBJECTIVE: The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia. STUDY DESIGN: Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using chi(2) tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a chi(2) test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate. RESULTS: Mean age (SD) at imaging was 59.5 (+/-4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m(2) (expressed as median [25th-75th percentile], 29.8 [25.9-33.7] vs 25.3 [23.1 32.0], P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval [CI], 1.39-9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95-7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21-8.49). CONCLUSION: In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies. PMID- 26874303 TI - Synthesis, characterization and biological approach of metal chelates of some first row transition metal ions with halogenated bidentate coumarin Schiff bases containing N and O donor atoms. AB - The impregnation of halogen atoms in a molecule is an emerging trend in pharmaceutical chemistry. The presence of halogens (Cl, Br, I and F) increases the lipophilic nature of molecule and improves the penetration of lipid membrane. The presence of electronegative halogen atoms increases the bio- activity of core moiety. In the present study, Co(II), Ni(II) and Cu(II) complexes are synthesised using Schiff bases (HL(I) and HL(II)), derived from 8-formyl-7-hydroxy-4 methylcoumarin/3-chloro-8-formyl-7-hydroxy-4-methylcoumarin with 2,4 difluoroaniline/o-toluidine respectively. The synthesized compounds were characterized by spectral (IR, NMR, UV-visible, Mass, ESI-MS, ESR), thermal, fluorescence and molar conductivity studies. All the synthesized metal complexes are completely soluble in DMF and DMSO. The non-electrolytic nature of the metal complexes was confirmed by molar conductance studies. Elemental analysis study suggest [ML2(H2O)2] stoichiometry, here M=Co(II), Ni(II) and Cu(II), L=deprotonated ligand. The obtained IR data supports the binding of metal ion to Schiff base. Thermal study suggests the presence of coordinated water molecules. Electronic spectral results reveal six coordinated geometry for the synthesized metal complexes. The Schiff bases and their metal complexes were evaluated for antibacterial (Pseudomonas aureginosa and Proteus mirabilis), antifungal (Aspergillus niger and Rhizopus oryzae), anthelmintic (Pheretima posthuma) and DNA cleavage (Calf Thymus DNA) activities. PMID- 26874304 TI - Affinity capture elution bridging assay: A novel immunoassay format for detection of anti-therapeutic protein antibodies. AB - BACKGROUND: Increased emphasis on the development of biologics has placed a significant focus on anti-drug antibody (ADA) detection. To address this need, several immunoassay formats have been described for use in characterizing potential immune responses. Two commonly utilized methods include the affinity capture elution (ACE) and bridging formats. While these approaches have been effective in supporting many clinical initiatives, both possess potential disadvantages. Here, we compare these standard methods to a novel format that addresses these noted drawbacks. RESULTS: A novel assay format has been designed to incorporate the benefits of the ACE and bridging methods while overcoming the disadvantages incurred with each approach. The described ACE-Bridge format exhibits excellent sensitivity and precision while providing superior drug tolerance when compared to bridging formats. Further, this assay format is not susceptible to the endogenous target interference that can be an issue in the ACE format. CONCLUSIONS: The ACE-Bridge format provides an often superior option as a screening method to monitor patient ADA responses. This method is unique in its ability to measure ADA in the presence of high circulating endogenous target concentrations (>100 ng/mL) while demonstrating very high drug tolerance. PMID- 26874302 TI - Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth. AB - BACKGROUND: The analysis of circulating microparticles in pregnancy is of revolutionary potential because it represents an in vivo biopsy of active gestational tissues. OBJECTIVE: We hypothesized that circulating microparticle signaling will differ in pregnancies that experience spontaneous preterm birth from those delivering at term and that these differences will be evident many weeks in advance of clinical presentation. STUDY DESIGN: Utilizing plasma specimens obtained between 10 and 12 weeks' gestation as part of a prospectively collected birth cohort in which pregnancy outcomes are independently validated by 2 board-certified maternal-fetal medicine physicians, 25 singleton cases of spontaneous preterm birth <= 34 weeks were matched by maternal age, race, and gestational age of sampling (+/-2 weeks) with 50 uncomplicated term deliveries. Circulating microparticles from these first-trimester specimens were isolated and analyzed by multiple reaction monitoring mass spectrometry for potential protein biomarkers following previous studies. Markers with robust univariate performance in correlating spontaneous preterm birth were further evaluated for their biological relevance via a combined functional profiling/pathway analysis and for multivariate performance. RESULTS: Among the 132 proteins evaluated, 62 demonstrated robust power of detecting spontaneous preterm birth in a bootstrap receiver-operating characteristic curve analysis at a false discovery rate of < 20% estimated via label permutation. Differential dependency network analysis identified spontaneous preterm birth-associated coexpression patterns linked to biological processes of inflammation, wound healing, and the coagulation cascade. Linear modeling of spontaneous preterm birth using a multiplex of the candidate biomarkers with a fixed sensitivity of 80% exhibited a specificity of 83% with median area under the curve of 0.89. These results indicate a strong potential of multivariate model development for informative risk stratification. CONCLUSION: This project has identified functional proteomic factors with associated biological processes that are already unique in their expression profiles at 10 12 weeks among women who go on to deliver spontaneously <= 34 weeks. These changes, with further validation, will allow the stratification of patients at risk of spontaneous preterm birth before clinical presentation. PMID- 26874305 TI - Developing and Implementing Major League Baseball's Health and Injury Tracking System. AB - In 2010, Major League Baseball and the Major League Baseball Players Association reached an agreement regarding the development and implementation of an electronic medical record system and a new league-wide injury surveillance system. The systems were developed to create a more efficient method to track medical histories of players longitudinally as they move across Major and Minor league affiliates, as well as to identify and monitor injury trends in the sport, identify areas of specific concern, and conduct epidemiologic research to better optimize player health and safety. The resulting injury surveillance system, the Health and Injury Tracking System (HITS), is a robust system that includes all players from the both the Major and Minor Leagues. HITS also allows for data linkage with other player- and game-level data to inform the development of injury prevention policies and programs. In the present article, we document the development and implementation of HITS; describe its utility for epidemiologic research; illustrate the potential analytic strength of the surveillance system and its ability to inform policy change; and note the potential for this new surveillance system to advance the field of sports injury epidemiology. PMID- 26874306 TI - In vitro and in vivo identification of tetradentated polyamine complexes as highly efficient metallodrugs against Trypanosoma cruzi. AB - In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), a series of tetraamine-based compounds was prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by PCR and reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels by (1)H NMR and TEM studies. Finally, as tetraamines are potentially capable of casuing oxidative damage in the parasites, the study was completed by assessing their activity as potential iron superoxide dismutase (Fe SOD) and trypanothione reductase (TR) inhibitors. High-selectivity indexes observed in vitro were the basis of promoting three of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Tetraamines 2 and 3 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression and curative rates of 33 and 50%, respectively. Tetraamine 3 turned out to be a great inhibitor of Fe-SOD and TR. The high anti-parasitic activity and low toxicity render these tetraamines appropriate molecules for the development of an affordable anti-Chagas agent. PMID- 26874307 TI - Beyond Content of Conversation. AB - Social interaction is pivotal to the formation of social relationships and groups. Much is known about the importance of interaction content (e.g., the transfer of information). The present review concentrates on the influence of the act of conversing on the emergence of a sense of solidarity, more or less independently of the content. Micro-characteristics of the conversation (e.g., brief silences, smooth turn-taking) can profoundly influence the emergence and the regulation of relationships and of solidarity. We suggest that this might be because the form of a conversation is experienced as an expression of the social structures within the group. Because of its dynamic nature, moreover, the form of conversation provides group members with a continuous gauge of the group's structural features (e.g., its hierarchy, social norms, and shared reality). Therefore, minor changes in the form and flow of group conversation can have considerable consequences for the regulation of social structure. PMID- 26874308 TI - Bioaugmentation for treatment of full-scale diethylene glycol monobutyl ether (DGBE) wastewater by Serratia sp. BDG-2. AB - A novel bacterial strain BDG-2 was isolated and used to augment the treatment of silicon plate manufacturing wastewater that primarily contains diethylene glycol monobutyl ether (DGBE). BDG-2 was identified as a Serratia sp. Under the optimal conditions of 30 degrees C, pH 9 and DGBE concentration of 2000 mg L(-1), the bioaugmented system achieved 96.92% COD removal after 39.9h. Laboratory-scale technological matching results indicated that, in a biofilm process with the addition of 100 mg L(-1) ammonia and 5 mg L(-1) total phosphorus (TP), 70.61% COD removal efficiency could be obtained in 46 h. Addition of polyaluminium chloride (PAC) to the reactors during the suspension process enhanced the settleability of the BDG-2 culture. Subsequently, successful start-up and stable operation of a full-scale bioaugmented treatment facilities were accomplished, and the volumetric organic load in the plug-flow aeration tank was 2.17 +/- 0.81 kg m(-3) d(-1). The effluent COD of the facilities was stable and always below 100 mg L( 1). PMID- 26874309 TI - Synthesis and application of a novel nanostructured ion-imprinted polymer for the preconcentration and determination of thallium(I) ions in water samples. AB - A novel synthesized nanostructured ion-imprinted polymer (IIP) was investigated for the determination of trace amount of thallium(I). For this purpose, the thallium(I) IIP particles were synthesized using methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker, methyl-2-[2-(2-2-[2-(methoxycarbonyl) phenoxy] ethoxyethoxy) ethoxy] benzoate as the chelating agent and 2,2-azobisisobutyronitrile (AIBN) as the initiator. The prepared IIP particles were characterized by field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR) and thermo gravimetric analysis (TGA). Various experimental factors such as pH, the amount of IIP particles, sorption and desorption time, sample volume, elution condition, and potentially interfering ions systematically examined. Under the optimum conditions, a sensitive response to Tl(I) within a wide concentration range (0.05 18 MUg L(-1)) was achieved. The limit of detection (LOD, 3Sb/m) was 6.3 ng L(-1). The maximum adsorption capacity of the novel imprinted adsorbent for Tl(I) was calculated to be 18.3 mg g(-1). The relative standard deviation (RSD) for eight replicate detections of 0.1 MUg L(-1) of thallium(I) was found to be 4.0%. An enrichment factor (EF) of 100 was obtained by this method. The proposed technique was successfully applied to monitoring thallium in different water samples and the certified reference material. PMID- 26874310 TI - Kinetics of aerobic cometabolic biodegradation of chlorinated and brominated aliphatic hydrocarbons: A review. AB - This review analyses kinetic studies of aerobic cometabolism (AC) of halogenated aliphatic hydrocarbons (HAHs) from 2001-2015 in order to (i) compare the different kinetic models proposed, (ii) analyse the estimated model parameters with a focus on novel HAHs and the identification of general trends, and (iii) identify further research needs. The results of this analysis show that aerobic cometabolism can degrade a wide range of HAHs, including HAHs that were not previously tested such as chlorinated propanes, highly chlorinated ethanes and brominated methanes and ethanes. The degree of chlorine mineralization was very high for the chlorinated HAHs. Bromine mineralization was not determined for studies with brominated aliphatics. The examined research period led to the identification of novel growth substrates of potentially high interest. Decreasing performance of aerobic cometabolism were found with increasing chlorination, indicating the high potential of aerobic cometabolism in the presence of medium- and low-halogenated HAHs. Further research is needed for the AC of brominated aliphatic hydrocarbons, the potential for biofilm aerobic cometabolism processes, HAH-HAH mutual inhibition and the identification of the enzymes responsible for each aerobic cometabolism process. Lastly, some indications for a possible standardization of future kinetic studies of HAH aerobic cometabolism are provided. PMID- 26874311 TI - Removal of heavy metals in wastewater by using zeolite nano-particles impregnated polysulfone membranes. AB - In this study, the adsorption and the filtration processes were coupled by a zeolite nanoparticle impregnated polysulfone (PSf) membrane which was used to remove the lead and the nickel cations from synthetically prepared solutions. The results obtained from X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis indicated that the synthesized zeolite nanoparticles, using conventional hydrothermal method, produced a pure NaX with ultrafine and uniform particles. The performance of the hybrid membrane was determined under dynamic conditions. The results also revealed that the sorption capacity as well as the water hydraulic permeability of the membranes could both be improved by simply tuning the membrane fabricating conditions such as evaporation period of the casting film and NaX loading. The maximum sorption capacity of the hybrid membrane for the lead and nickel ions was measured as 682 and 122 mg/g respectively at the end of 60 min of filtration, under 1 bar of transmembrane pressure. The coupling process suggested that the membrane architecture could be efficiently used for treating metal solutions with low concentrations and transmembrane pressures. PMID- 26874312 TI - Fabrication of highly hydrophobic organic-inorganic hybrid magnetic polysulfone microcapsules: A lab-scale feasibility study for removal of oil and organic dyes from environmental aqueous samples. AB - In this work, three kinds of organic-inorganic hybrid materials (vinyl benzene linear polymer modified SBA-15, attapulgite and halloysite nanotubes) in the shape of powder and the corresponding magnetic polysulfone microcapsules were developed for removal of oil and dyes from environmental aqueous samples, respectively. As determined from the oil and dye adsorption studies, the developed magnetic polysulfone microcapsules exhibited high adsorption capacity of 13.8-17.3g/g for oil. The prepared functionalized materials and the corresponding microcapsules can remove 85.0-91.6% and 81.8-87.8% Sudan I in 80 min and 7.6h, respectively. The results showed a significant improvement in their adsorption capacities and removal efficiencies compared to the parent matrices, indicating that the introducing of the vinyl benzene linear polymer was a major factor in the removal of the hydrophobic pollutants. At the same time, the adsorption capacity for the investigated pollutants also depended on the textural feature of matrix itself. In view of the utilization of low-cost clay minerals (attapulgite and halloysite nanotubes), these proposed functionalized materials and the corresponding magnetic polysulfone microcapsules had a great promise to be used as an efficient sorbent for removal of pollutants from environmental aqueous samples. PMID- 26874313 TI - Brominated flame retardants in the surrounding soil of two manufacturing plants in China: Occurrence, composition profiles and spatial distribution. AB - Surface soil samples were collected surrounding two brominated flame retardants (BFRs) manufacturing plants in China in August 2014 and analyzed for 23 polybrominated diphenyl ethers (PBDEs) and 8 novel brominated flame retardants (NBFRs). BDE209 and decabromodiphenylethane (DBDPE) were the predominant compounds in soil with the median levels of 1600 and 560 ng/g dw, respectively. The PBDEs profiles in soil samples were consistent with that of commercial product (comDecaBDE). The percentage contributions to total PBDEs decreased from higher to lower brominated homologues. Lower concentrations of NBFRs (excluding DBDPE) were detected in soil surrounding the two plants, suggesting they are byproducts or degradation products of the manufacturing activities. The concentrations of most BFRs dropped exponentially within 3-5 km of the manufacturing plants, suggesting recent deposition of these compounds to the soil. Directional distribution indicated that PBDEs and DBDPE concentrations were highest in the north direction of Plants 1. Three-day air parcel forward trajectories confirmed that the air parcel was responsible for the higher concentration of BFRs in the soil of north direction of the plant. PMID- 26874314 TI - Municipal composts reduce the transfer of Cd from soil to vegetables. AB - Cadmium (Cd) is a non-essential trace element that accumulates in agricultural soils through the application of Cd-rich phosphate fertiliser. Vegetables can accumulate Cd to concentrations that sometimes exceed food safety standards. We investigated the potential of low-cost soil amendments to reduce Cd uptake by spinach (Spinacia oleracea L.), lettuce (Lactuca sativa L.) and onion (Allium cepa L.). Batch sorption experiments revealed the relative sorption of Cd by biosolids, charcoal, lignite, sawdust, two types of compost, bentonite and zeolite. Lignite and compost had the greatest ability to sorb Cd and were subsequently selected for pot trials, which elucidated their effect on Cd uptake by onions, spinach and lettuce in two market garden soils with native Cd concentrations of 1.45 mg/kg and 0.47 mg/kg. The addition of 2.5% (dry w/w) municipal compost reduced the Cd concentration in onions, spinach and lettuce by up to 60% in both soils. The addition of lignite gave variable results, which depended on the soil type and rate of addition. This Cd immobilisation was offset by soil acidification caused by the lignite. The results indicate that municipal compost is a low-cost soil conditioner that is effective in reducing plant Cd uptake. PMID- 26874315 TI - Analysis of Kidney Ultrasound Dimensions by Body Habitus and Position. AB - PURPOSE: Renal dimensions are an important assessment of the genitourinary tract used to evaluate critical aspects of renal growth and development. Understanding the effect of patient position is important to use and interpret these parameters. In this prospective study we determined the effect of patient position and general body habitus on renal length and parenchymal area in children undergoing renal ultrasound. MATERIALS AND METHODS: Between October 2010 and January 2011 children underwent renal ultrasound while prone and supine. Bilateral renal length and renal parenchymal area were measured. Pearson and Bland-Altman statistical analyses were used to examine correlations, measurement bias and the degree of agreement between methods. RESULTS: Renal length measurements in both positions were complete for 201 right and 196 left kidneys. Parenchymal area measurements were complete for both kidneys in 177 children. When compared individually, supine and prone measures of renal length and parenchymal area highly correlated on Pearson analysis (greater than 0.96 and greater than 0.89, respectively). When compared by method, Bland-Altman analyses of differences vs means showed greater than 50% variance, representing wide limits of agreement with poor interrelation. Neither persistent systematic bias nor body habitus influenced results. CONCLUSIONS: While Pearson analysis showed high correlation for supine and prone renal measurements, Bland-Altman analysis of renal length and parenchymal area demonstrated wide limits of agreement, not allowing interchangeable use of prone and supine measurements. As such, renal ultrasound should specify standardized positions and benchmarks. These results provide guidance to standardize renal ultrasound measurements when renal size is used as an indicator of kidney health. PMID- 26874316 TI - Prospective Assessment of Radiation in Pediatric Urology: The Pediatric Urology Radiation Safety Evaluation Study. AB - PURPOSE: Pediatric tissues are exquisitely sensitive to ionizing radiation from diagnostic studies and therapies involving fluoroscopy. We prospectively monitored radiation exposure in our pediatric urology patients during fluoroscopy guided operative procedures with single point dosimeters to quantify radiation dose. MATERIALS AND METHODS: Children undergoing fluoroscopy guided urological procedures were prospectively enrolled in the study from 2013 to 2015. Single point dosimeters were affixed to skin overlying the procedural site for the durations of the procedures to record dosimetry data. Patient demographics, procedural variables and fluoroscopic settings were recorded. RESULTS: A total of 78 patients underwent 96 procedures, including retrograde pyelography, ureteral stent insertion, ureteroscopy and percutaneous nephrolithotomy. Median patient age was 12 years (range 0.3 to 17) and median body mass index percentile for age was 70.7 (1.0 to 99.1). Median skin entrance radiation dose for all procedures performed was 0.56 mGy. Median dosages associated with the 29 diagnostic procedures and 49 definitive interventions were 0.6 mGy (mean 0.8, range 0.1 to 2.2) and 0.7 mGy (1.1, 0.0 to 5.5), respectively. The dose associated with the 18 procedures of temporization was significantly higher by comparison (median 1.0 mGy, mean 2.6, range 0.1 to 10.7, p = 0.02). CONCLUSIONS: Pediatric radiation exposure is not insignificant during urological procedures. Further multi institutional work would provide context for our findings. Protocols to optimize fluoroscopic settings and minimize patient exposure, and guidelines for radiation based imaging should have a key role in all pediatric radiation safety initiatives. PMID- 26874317 TI - A combined non-targeted and targeted metabolomics approach to study the stereoselective metabolism of benalaxyl enantiomers in mouse hepatic microsomes. AB - Understanding of xenobiotic metabolism is necessary for risk assessment as well as toxicological research. In the present study, nanoLC/LTQ-Orbitrap mass based non-targeted metabolomics method coupled with ultra-performance liquid chromatography (UPLC)/triple quadrupole mass based targeted metabolomics method was carried out to investigate the stereoselective metabolism of benalaxyl in mouse hepatic microsomes. As a result, 7 metabolites of benalaxyl were identified, including 5 previously reported and 2 newly identified metabolites in present work. Hydroxylation, oxidation and esterolysis were major biotransformation reactions of benalaxyl in mouse hepatic microsomes. For stereoselective metabolism study, (-)-R-benalaxyl degraded much faster than its antipode with the t1/2 of 81.24 and 190.38 min for (-)-R- and (+)-S-benalaxyl, respectively. More importantly, stereoselectivity was also observed in the formation of the identified metabolites. In conclusion, the combined use of the mass spectrometry based targeted and non-targeted metabolomics provided a new approach to investigate stereoselective metabolism and identify novel metabolites of chiral pesticides. This study highlights the stereoselective metabolic profile of benalaxyl enantiomers and provides reliable data for benalaxyl toxicological risk assessment in mammal. PMID- 26874318 TI - Mercury remediation in wetland sediment using zero-valent iron and granular activated carbon. AB - Wetlands are hotspots for production of toxic methylmercury (MeHg) that can bioaccumulate in the food web. The objective of this study was to determine whether the application of zero-valent iron (ZVI) or granular activated carbon (GAC) to wetland sediment could reduce MeHg production and bioavailability to benthic organisms. Field mesocosms were installed in a wetland fringing Hodgdon Pond (Maine, USA), and ZVI and GAC were applied. Pore-water MeHg concentrations were lower in treated compared with untreated mesocosms; however, sediment MeHg, as well as total Hg (THg), concentrations were not significantly different between treated and untreated mesocosms, suggesting that smaller pore-water MeHg concentrations in treated sediment were likely due to adsorption to ZVI and GAC, rather than inhibition of MeHg production. In laboratory experiments with intact vegetated sediment clumps, amendments did not significantly change sediment THg and MeHg concentrations; however, the mean pore-water MeHg and MeHg:THg ratios were lower in the amended sediment than the control. In the laboratory microcosms, snails (Lymnaea stagnalis) accumulated less MeHg in sediment treated with ZVI or GAC. The study results suggest that both GAC and ZVI have potential for reducing MeHg bioaccumulation in wetland sediment. PMID- 26874319 TI - Variability of PCB burden in 5 fish and sharks species of the French Mediterranean continental slope. AB - Despite being generally located far from contamination sources, deep marine ecosystems are impacted by chemicals like PCB. The PCB contamination in five fish and shark species collected in the continental slope of the Gulf of Lions (NW Mediterranean Sea) was measured, with a special focus on intra- and interspecific variability and on the driving factors. Significant differences occurred between species. Higher values were measured in Scyliorhinus canicula, Galeus melastomus and Helicolenus dactylopterus and lower values in Phycis blennoides and Lepidorhombus boscii. These differences might be explained by specific abilities to accumulate and eliminate contaminant, mostly through cytochrome P450 pathway. Interindividual variation was also high and no correlation was observed between contamination and length, age or trophic level. Despite its major importance, actual bioaccumulation of PCB in deep fish is not as documented as in other marine ecosystems, calling for a better assessment of the factors driving individual bioaccumulation mechanisms and originating high variability in PCB contamination. PMID- 26874320 TI - Assessing estuarine quality: A cost-effective in situ assay with amphipods. AB - In situ assays based on feeding depression can be powerful ecotoxicological tools that can link physiological organism-level responses to population and/or community-level effects. Amphipods are traditional target species for toxicity tests due to their high sensitivity to contaminants, availability in the field and ease of handling. However, cost-effective in situ assays based on feeding depression are not yet available for amphipods that inhabit estuarine ecosystems. The aim of this work was to assess a short-term in situ assay based on postexposure feeding rates on easily quantifiable food items with an estuarine amphipod. Experiments were carried out under laboratory conditions using juvenile Echinogammarus marinus as the target individual. When 60 Artemia franciscana nauplii (as prey) were provided per individual for a period of 30 min in dark conditions, feeding rates could be easily quantified. As an endpoint, postexposure feeding inhibition in E. marinus was more sensitive to cadmium contamination than mortality. Assay calibration under field conditions demonstrated the relevance of sediment particle size in explaining individual feeding rates in uncontaminated water bodies. An evaluation of the 48-h in situ bioassay based on postexposure feeding rates indicated that it is able to discriminate between unpolluted and polluted estuarine sites. Using the harmonized protocol described here, the in situ postexposure feeding assay with E. marinus was found to be a potentially useful, cost-effective tool for assessing estuarine sediment and water quality. PMID- 26874321 TI - Transformation of ionophore antimicrobials in poultry litter during pilot-scale composting. AB - Ionophores are the second top selling class of antimicrobials used in food producing animals in the United States. In chickens, ionophores are used as feed additives to control coccidiosis; up to 80% of administered ionophores are excreted in the litter. Because poultry litter is commonly used to fertilize agricultural fields, ionophore residues in litter have become contaminants of emerging concern. This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify ionophores, and identify their transformation products (TPs) in poultry litter after on-farm pilot-scale composting. The validation parameters of the optimized method showed good accuracy, ranging from 71 to 119% recovery and relative standard deviation (precision) of <=19% at three different concentration levels (10, 50 and 100 MUg/kg). Monensin, salinomycin and narasin, were detected in the poultry litter samples prior to composting at 290.0 +/- 40, 426 +/- 46, and 3113 +/- 318 MUg kg( 1), respectively. This study also aims to investigate the effect of different composting conditions on the removal of ionophores, such as the effect of turning or aeration. Results revealed a 13-68% reduction in ionophore concentrations after 150 d of composting, depending on whether the compost was aerated, turned, or subjected to a combination of both aeration and turning. Three transformation products and one metabolite of ionophores were identified in the composted litter using high-resolution liquid chromatography with quadrupole time-of-flight mass spectrometry (LC-QToF/MS). PMID- 26874322 TI - Benzotriazole UV stabilizers in sediments, suspended particulate matter and fish of German rivers: New insights into occurrence, time trends and persistency. AB - Benzotriazole UV stabilizers (BUVSs) are widely applied in plastics to prevent discoloration and to enhance product stability. This study describes for the first time the occurrence of nine different lipophilic BUVSs (UV-326, UV-320, UV 329, UV-350, UV-328, UV-327, UV-928, UV-234 and UV-360) in sediment, suspended particulate matter (SPM) and bream liver samples of German rivers. All investigated BUVSs were detected in sediments and SPM at concentrations in the low ng/g dry weight (dw) range. The so far rarely analyzed compound UV-360 as well as UV-326 were the predominant BUVSs in sediments and SPM from the river Rhine reaching maximum concentrations of 62 and 44 ng/g dw, respectively. Five BUVSs were also confirmed to bioaccumulate in bream liver, but neither UV-360 nor UV-326 was detected above the limit of quantification (LOQ). In contrast, highest concentrations in bream liver were determined for UV-327 (65 ng/g dw) and UV-328 (40 ng/g dw). A retrospective time trend analysis of BUVSs in SPM from two sites (river Rhine, 2005 to 2013; river Saar, 2006 to 2013) revealed increasing contamination levels of UV-329 and decreasing levels of UV-320 and UV-350. At one site (river Rhine) time trends of BUVS concentrations were also investigated in bream liver (1995-2013) and supported a considerably reduced exposure to UV-350. A first assessment of the environmental fate of BUVSs by sediment-water batch systems revealed a rapid partitioning into the sediment and no considerable degradation within 100 d. PMID- 26874323 TI - Seizure facilitating activity of the oral contraceptive ethinyl estradiol. AB - Contraceptive management is critical in women with epilepsy. Although oral contraceptives (OCs) are widely used by many women with epilepsy, little is known about their impact on epileptic seizures and epileptogenesis. Ethinyl estradiol (EE) is the primary component of OC pills. In this study, we investigated the pharmacological effect of EE on epileptogenesis and kindled seizures in female mice using the hippocampus kindling model. Animals were stimulated daily with or without EE until generalized stage 5 seizures were elicited. EE treatment significantly accelerated the rate of epileptogenesis. In acute studies, EE caused a significant decrease in the afterdischarge threshold and increased the incidence and severity of seizures in fully-kindled mice. In chronic studies, EE treatment caused a greater susceptibility to kindled seizures. Collectively, these results are consistent with moderate proconvulsant-like activity of EE. Such excitatory effects may affect seizure risk in women with epilepsy taking OC pills. PMID- 26874324 TI - Oral administration of acarbose ameliorates imiquimod-induced psoriasis-like dermatitis in a mouse model. AB - Psoriasis is a chronic autoimmune disease of undefined etiology that involves dysregulated interplay between immune cells and keratinocytes. Acarbose was found to decrease inflammatory parameters in diabetic patients in addition to its anti diabetic effects. Here, we report that imiquimod (IMQ)-induced epidermal hyperplasia and psoriasis like-inflammation were significantly inhibited by acarbose treatment. Real-time PCR showed that mRNA levels of the cytokines TNF alpha, IL-6, IL-1beta IL-17A, and IL-22 in skin were also decreased significantly by acarbose. In addition, we found that acarbose reduced infiltration of CD3(+) T cells and GR-1(+) neutrophils in lesional skin and also reduced the percentage of IL-17-producing CD4(+) T cells (Th17) and IL-17- and IL-22-producing gammadelta T cells in the spleen. In contrast, acarbose increased the frequency of IL-10 producing CD4(+) regulator Tr1 T cells in the spleen and small intestine. These results indicate that oral administration of acarbose can attenuate the severity of imiquimod-induced psoriasis with local and systemic anti-inflammatory and immune modulation effects, thus suggesting that acarbose is an effective therapeutic strategy for psoriasis regulation. PMID- 26874326 TI - Attributes of patient-centered primary care associated with the public perception of good healthcare quality in Brazil, Colombia, Mexico and El Salvador. AB - This study evaluated primary care attributes of patient-centered care associated with the public perception of good quality in Brazil, Colombia, Mexico and El Salvador. We conducted a secondary data analysis of a Latin American survey on public perceptions and experiences with healthcare systems. The primary care attributes examined were access, coordination, provider-patient communication, provision of health-related information and emotional support. A double-weighted multiple Poisson regression with robust variance model was performed. The study included between 1500 and 1503 adults in each country. The results identified four significant gaps in the provision of primary care: not all respondents had a regular place of care or a regular primary care doctor (Brazil 35.7%, Colombia 28.4%, Mexico 22% and El Salvador 45.4%). The communication with the primary care clinic was difficult (Brazil 44.2%, Colombia 41.3%, Mexico 45.1% and El Salvador 56.7%). There was a lack of coordination of care (Brazil 78.4%, Colombia 52.3%, Mexico 48% and El Salvador 55.9%). Also, there was a lack of information about healthy diet (Brazil 21.7%, Colombia 32.9%, Mexico 16.9% and El Salvador 20.8%). The public's perception of good quality was variable (Brazil 67%, Colombia 71.1%, Mexico 79.6% and El Salvador 79.5%). The primary care attributes associated with the perception of good quality were a primary care provider 'who knows relevant information about a patient's medical history', 'solves most of the health problems', 'spends enough time with the patient', 'coordinates healthcare' and a 'primary care clinic that is easy to communicate with'. In conclusion, the public has a positive perception of the quality of primary care, although it has unfulfilled expectations; further efforts are necessary to improve the provision of patient-centered primary care services in these four Latin American countries. PMID- 26874325 TI - Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice. AB - BACKGROUND: Plasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies. METHOD: Female A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at -20 degrees C for subsequent testing. RESULTS: Both domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the 20-mer peptide sequences comprising the last 8aa of D and first 12aa of C of the two allelic families and the first 20aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium-derived MSP2 and inhibiting parasite growth in ADCI. CONCLUSION: The data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials. PMID- 26874327 TI - Barriers to healthcare coordination in market-based and decentralized public health systems: a qualitative study in healthcare networks of Colombia and Brazil. AB - Although integrated healthcare networks (IHNs) are promoted in Latin America in response to health system fragmentation, few analyses on the coordination of care across levels in these networks have been conducted in the region. The aim is to analyse the existence of healthcare coordination across levels of care and the factors influencing it from the health personnel' perspective in healthcare networks of two countries with different health systems: Colombia, with a social security system based on managed competition and Brazil, with a decentralized national health system. A qualitative, exploratory and descriptive-interpretative study was conducted, based on a case study of healthcare networks in four municipalities. Individual semi-structured interviews were conducted with a three stage theoretical sample of (a) health (112) and administrative (66) professionals of different care levels, and (b) managers of providers (42) and insurers (14). A thematic content analysis was conducted, segmented by cases, informant groups and themes. The results reveal poor clinical information transfer between healthcare levels in all networks analysed, with added deficiencies in Brazil in the coordination of access and clinical management. The obstacles to care coordination are related to the organization of both the health system and the healthcare networks. In the health system, there is the existence of economic incentives to compete (exacerbated in Brazil by partisan political interests), the fragmentation and instability of networks in Colombia and weak planning and evaluation in Brazil. In the healthcare networks, there are inadequate working conditions (temporary and/or part-time contracts) which hinder the use of coordination mechanisms, and inadequate professional training for implementing a healthcare model in which primary care should act as coordinator in patient care. Reforms are needed in these health systems and networks in order to modify incentives, strengthen the state planning and supervision functions and improve professional working conditions and skills. PMID- 26874328 TI - Conflicts of Interest and Solicited Replication Attempts. PMID- 26874329 TI - Racial and Ethnic Differences in What Smokers Report Paying for Their Cigarettes. AB - INTRODUCTION: Smoking rates and tobacco-related health problems vary by race and ethnicity. We explore whether cigarette prices, a determinant of tobacco use, differ across racial and ethnic groups, and whether consumer behaviors influence these differences. METHODS: We used national Tobacco Use Supplement data from 23 299 adult smokers in the United States to calculate average reported cigarette pack prices for six racial and ethnic groups. Using multivariate regression models, we analyzed the independent effect of race and ethnicity on price, and whether these effects changed once indicators of carton purchasing, menthol use, Indian reservation purchase, and state market prices were incorporated. RESULTS: American Indians and whites pay similar amounts and report the lowest prices. Blacks, Hispanics, and Asians reported paying $0.42, $0.68, and $0.89 more for a pack of cigarettes than whites. After accounting for differences in consumer behaviors, these gaps shrunk to $0.27, $0.29, and $0.27, respectively, while American Indians paid $0.38 more than whites. Pack buying was associated with $0.99 higher per-pack prices than carton buying, which was most common among whites. Additionally, people who purchased off an Indian reservation reporting paying $1.54 more than those who purchased on reservation. CONCLUSIONS: Average reported cigarette prices vary by race and ethnicity, in part due to differences in product use and purchase location. Tobacco price policies, especially those that target low prices for multipack products or on Indian reservations may increase the prices paid by whites and American Indians, who smoke at the highest rates and pay the least per pack. IMPLICATIONS: This study examines differences in reported prices paid by different racial and ethnic groups, using recent, national data from the United States. Results indicating that racial and ethnic groups that smoke at the highest rates (American Indians and whites) also pay the least are consistent with evidence that price is a key factor in cigarette use. Additional analysis finds that cigarette purchasing behaviors, especially carton buying and purchasing on Indian reservations, partially account for the documented price differences, and suggest that policies focused on bulk purchases (carton, multipack) and reservation prices have strong tobacco control potential. PMID- 26874331 TI - Running to Forget. PMID- 26874330 TI - Naltrexone but Not Ketanserin Antagonizes the Subjective, Cardiovascular, and Neuroendocrine Effects of Salvinorin-A in Humans. AB - BACKGROUND: Salvinorin-A is a terpene found in the leaves of the plant Salvia divinorum. When administered to humans, salvinorin-A induces an intense but short lasting modified state of awareness, sharing features with those induced by the classical serotonin-2A receptor agonist psychedelics. However, unlike substances such as psilocybin or mescaline, salvinorin-A shows agonist activity at the kappa opioid receptor rather than at the serotonin-2A receptor. Here, we assessed the involvement of kappa-opioid receptor and serotonin-2A agonism in the subjective, cardiovascular, and neuroendocrine effects of salvinorin-A in humans. METHODS: We conducted a placebo-controlled, randomized, double-blind study with 2 groups of 12 healthy volunteers with experience with psychedelic drugs. There were 4 experimental sessions. In group 1, participants received the following treatment combinations: placebo+placebo, placebo+salvinorin-A, naltrexone+placebo, and naltrexone+salvinorin-A. Naltrexone, a nonspecific opioid receptor antagonist, was administered at a dose of 50mg orally. In group 2, participants received the treatment combinations: placebo+placebo, placebo+salvinorin-A, ketanserin+placebo, and ketanserin+salvinorin-A. Ketanserin, a selective serotonin-2A antagonist, was administered at a dose of 40mg orally. RESULTS: Inhalation of 1mg of vaporized salvinorin-A led to maximum plasma concentrations at 1 and 2 minutes after dosing. When administered alone, salvinorin-A severely reduced external sensory perception and induced intense visual and auditory modifications, increased systolic blood pressure, and cortisol and prolactin release. These effects were effectively blocked by naltrexone, but not by ketanserin. CONCLUSIONS: Results support kappa opioid receptor agonism as the mechanism of action underlying the subjective and physiological effects of salvinorin-A in humans and rule out the involvement of a serotonin-2A-mediated mechanism. PMID- 26874332 TI - Combining chemical and genetic approaches for development of responsive FRET based sensor systems for protein kinases. AB - Chemical and genetic approaches were combined for the development of responsive FRET-based sensor systems for protein kinases, using PIM2 as the model kinase. Fusions of PIM2 and a red fluorescent protein, TagRFP were expressed in mammalian cells and small-molecule ARC-Lum photoluminescent probes possessing different phosphorescent and fluorescent properties were constructed. Based on a variety of Forster-type resonant energy transfer (FRET) mechanisms (including intermolecular or intramolecular energy transfer and transfer between singlet-singlet or triplet singlet electronic states of interacting luminophores) of the probe and that of the fluorescently tagged PIM2, FRET-based sensor systems were constructed. The developed assays can be applied for analysis of PIM2 in biological samples and screening and characterization of PIM2 inhibitors in cell lysates. In screening studies sub-micromolar affinity of a d-arginine-rich peptide, nona(d-arginine) amide [(d-Arg)9-NH2], towards PIM2 was discovered that points to possible specific effect of this widely used transport peptide to cellular protein phosphorylation balance. PMID- 26874333 TI - Shimming Halbach magnets utilizing genetic algorithms to profit from material imperfections. AB - In recent years, permanent magnet-based NMR spectrometers have resurfaced as low cost portable alternatives to superconducting instruments. While the development of these devices as well as clever shimming methods have yielded impressive advancements, scaling the size of these magnets to miniature lengths remains a problem to be addressed. Here we present the results of a study of a discrete shimming scheme for NMR Mandhalas constructed from a set of individual magnet blocks. While our calculations predict a modest reduction in field deviation by a factor of 9.3 in the case of the shimmed ideal Mandhala, a factor of 28 is obtained in the case of the shimmed imperfect Mandhala. This indicates that imperfections of magnet blocks can lead to improved field homogeneity. We also present a new algorithm to improve the homogeneity of a permanent magnet assembly. Strategies for future magnet construction can improve the agreement between simulation and practical implementation by using data from real magnets in these assemblies as the input to such an algorithm to optimize the homogeneity of a given design. PMID- 26874334 TI - Paths of water entry and structures involved in the breaking of seed dormancy of Lupinus. AB - Physical dormancy is the water impermeability of the seed coat caused by one or more palisade cell layer(s) called macrosclereids. The specialised structure for water entry sites is the water gap, which serves as a detector of environmental cues for germination. In Fabaceae, the water gap is the lens, although another seed structure for water entry could exist. In this study, we identified the initial site of water entry, observed the hydration of a cushion-like structure near the radicle, described the anatomy of the water gap, and analysed the association of anatomical seed traits with the initial site of water entry and the imbibition velocity of six species of Lupinus from the state of Jalisco, Mexico. Dye tracking with a toluidine blue solution was used to identify the initial site of water entry. The anatomical description was performed using conventional microtechnique and a light microscope. The entry of the toluidine solution into seeds of L. montanus was observed after 6h, followed by L. exaltatus and L. mexicanus after 18h and L. elegans, L. reflexus and L. rotundiflorus after 48h. The site of water entry was the lens in L. elegans, L. exaltatus, L. reflexus and L. rotundiflorus and the micropyle in L. mexicanus and L. montanus. The cushion-like structure was responsible for water accumulation in embryo imbibition. Significant differences among anatomical seed traits such as thickness in the hilar region, the counter-palisade layer, cushion-like structure, epidermis, hypodermis, and innermost parenchyma layer were found among the species. PMID- 26874335 TI - High-performance liquid chromatographic enantioseparation of fluorinated cyclic beta(3) -amino acid derivatives on polysaccharide-based chiral stationary phases. Comparison with nonfluorinated counterparts. AB - The stereoisomers of five fluorinated cyclic beta(3) -amino acid derivatives and their nonfluorinated counterparts were separated on chiral stationary phases containing as chiral selectors cellulose tris-(3,5-dimethylphenyl carbamate), cellulose tris-(3-chloro-4-methylphenyl carbamate), cellulose tris-(4 methylbenzoate), cellulose tris-(4-chloro-3-methylphenyl carbamate), amylose tris (3,5-dimethylphenyl carbamate) or amylose tris-(5-chloro-2-methylphenyl carbamate). The enantioseparations were carried out in normal-phase mode with n hexane/alcohol/alkylamine mobile phases in the temperature range 5-40 degrees C. The effects of the mobile phase composition, the nature and concentration of the alcohol and alkylamine additives, the structures of the analytes and temperature on the separations were investigated. Thermodynamic parameters were calculated from plots of ln alpha vs. 1/T. The Delta(DeltaH degrees ) values ranged between 5.0 and +1.6 kJ/mol, while Delta(DeltaS degrees ) varied between -12.6 and +5.7 J/mol/K. The enantioseparation was enthalpically controlled, the retention factor and the separation factor decreasing with increasing temperature, but entropically controlled separation was also observed. The elution sequence was determined for all of the investigated analytes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26874336 TI - Coronary microvascular function in patients with type 2 diabetes mellitus. AB - AIMS: The aims of this study were to compare the index of microcirculatory resistance (IMR) and its determinants in diabetes mellitus (DM) and non-DM patients with vascular risk factors, and to evaluate the potential differential involvement of coronary microvascular beds. METHODS AND RESULTS: Fifty-six patients (32 with DM), without significant epicardial coronary disease, had IMR measured in the anterior and posterior circulations. There was no significant difference in the anterior compared to posterior circulation IMR in the whole group (27 vs. 26, p=0.92) or in the DM subgroup (35 vs. 28, p=0.31). DM patients had higher anterior circulation IMR compared to non-DM patients (27 vs. 15, p=0.009). Posterior circulation IMR was higher than anterior circulation IMR in non-DM patients (25 vs. 16, p=0.01). Multivariate determinants of higher anterior circulation IMR in DM were dyslipidaemia, hypertension, worsening glycaemic control, and higher body mass index; metformin had a protective effect. CONCLUSIONS: There is differential involvement of the coronary microvascular beds. In the presence of risk factors, microvascular function of the posterior circulation was affected before the anterior; DM patients had worse microvascular function in the anterior but not posterior circulation compared to patients without DM. Vascular risk factors, including DM, adversely affect coronary microvascular function, and their treatment was associated with improvement. PMID- 26874337 TI - QSARs for estimating intrinsic hepatic clearance of organic chemicals in humans. AB - Quantitative structure-activity relationships (QSARs) were developed to predict the in vitro clearance (CLINT) of xenobiotics metabolised in human hepatocytes (118 compounds) and microsomes (115 compounds). Clearance values were gathered from the scientific literature and multiple linear models were built and validated selecting at most 6 predictors from a pool of over 2000 potential molecular descriptors. For the hepatocytes QSAR, the explained variance (Radj(2)) was 67% and the predictive ability (Rext(2)) was 62%. For the microsomes QSAR, Radj(2) was 50% and Rext(2) 30%. For both liver assays, the most important descriptor relates to electronic properties of the compound. Functional groups of fragments were useful to identify specific compounds that have a deviating reaction rate compared to the others, such as polychlorobiphenyls (PCBs) and organic amides which were poorly metabolised by hepatocytes and microsomes, respectively. For hepatocytes, clearance was predominantly determined by electronic characteristics, while size and shape characteristics were less important and partitioning properties were absent. This may suggest that uptake across the membrane and enzyme binding are not rate-limiting steps. Particularly for hepatocytes the QSAR statistics are encouraging, allowing application of the outcomes in in vitro to in vivo extrapolation. PMID- 26874338 TI - Cherry Picking Patients: Examining the Interval Between Patient Rooming and Resident Self-assignment. AB - OBJECTIVE: We aimed to evaluate the association between patient chief complaint and the time interval between patient rooming and resident physician self assignment ("pickup time"). We hypothesized that significant variation in pickup time would exist based on chief complaint, thereby uncovering resident preferences in patient presentations. METHODS: A retrospective medical record review was performed on consecutive patients at a single, academic, university based emergency department with over 50,000 visits per year. All patients who presented from August 1, 2012, to July 31, 2013, and were initially seen by a resident were included in the analysis. Patients were excluded if not seen primarily by a resident or if registered with a chief complaint associated with trauma team activation. Data were abstracted from the electronic health record (EHR). The outcome measured was "pickup time," defined as the time interval between room assignment and resident self-assignment. We examined all complaints with >100 visits, with the remaining complaints included in the model in an "other" category. A proportional hazards model was created to control for the following prespecified demographic and clinical factors: age, race, sex, arrival mode, admission vital signs, Emergency Severity Index code, waiting room time before rooming, and waiting room census at time of rooming. RESULTS: Of the 30,382 patients eligible for the study, the median time to pickup was 6 minutes (interquartile range = 2-15 minutes). After controlling for the above factors, we found systematic and significant variation in the pickup time by chief complaint, with the longest times for patients with complaints of abdominal problems, numbness/tingling, and vaginal bleeding and shortest times for patients with ankle injury, allergic reaction, and wrist injury. CONCLUSIONS: A consistent variation in resident pickup time exists for common chief complaints. We suspect that this reflects residents preferentially choosing patients with simpler workups and less perceived diagnostic ambiguity. This work introduces pickup time as a metric that may be useful in the future to uncover and address potential physician bias. Further work is necessary to establish whether practice patterns in this study are carried beyond residency and persist among attendings in the community and how these patterns are shaped by the information presented via the EHR. PMID- 26874341 TI - Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida. AB - The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure period of 2 days; and mortality, weight loss, enzymatic activities (cholinesterase, lactate dehydrogenase and alkaline phosphatase) and histopathological effects after an exposure period of 14 days. Carbendazim was found to be highly toxic to E. fetida (LC50=2mg/kg d.w.), significantly reducing earthworm weight and showing an avoidance response at soil concentrations that are close to those predicted in rice-fields and in surrounding ecosystems. The insecticide dimethoate showed a moderate acute toxicity (LC50=28mg/kg d.w.), whereas the rest of tested pesticides showed low toxicity potential (LC50 values above 100mg/kg d.w.). For these pesticides, however, weight loss was identified as a sensitive endpoint, with NOEC values approximately 2 times or lower than the calculated LC10 values. The investigated effects on the enzymatic activities of E. fetida and the observed histopathological alterations (longitudinal and circular muscle lesions, edematous tissues, endothelial degeneration and necrosis) proved to be sensitive biomarkers to monitor pesticide contamination and are proposed as alternative measures to evaluate pesticide risks on agro-ecosystems. PMID- 26874342 TI - The expression of human beta-defensins (hBD-1, hBD-2, hBD-3, hBD-4) in gingival epithelia. AB - OBJECTIVE: The aim of this study was to analyze and compare the expression patterns of human beta-defensin-4 (hBD-4) with those of hBD-1, hBD-2, and hBD-3 in healthy and chronically inflamed gingival tissues. MATERIALS AND METHODS: A total of 96 gingival samples were collected, comprising 46 biopsies from chronic periodontitis (CP) patients and 50 from individuals with healthy tissue. Of these, 21CP and 21 healthy samples were used to examine the protein expression of the hBDs by immunohistochemistry. The remaining 25CP and 29 healthy tissue samples were subjected to real-time reverse transcription polymerase chain reaction to quantify the mRNA expression of the hBDs. RESULTS: All four types of beta-defensin peptides were confined to the gingival epithelia. The percentage of samples positive for hBD-4 mRNA was significantly lower than the percentages for the other three beta-defensins, both in healthy (p=0.003) and in inflamed (p=0.030) gingiva. However, in the case of the relative mRNA expression levels, that of hBD-4 was significantly higher than the levels for hBD-2 (healthy group: p<0.01; CP group: p<0.01) and hBD-3 (healthy group: p=0.004; CP group: p<0.01). CONCLUSIONS: Our study demonstrates differential expression of hBD-1, hBD-2, hBD 3, and hBD-4 in healthy and CP gingiva. PMID- 26874343 TI - An investigation into the butyrylcholinesterase-catalyzed hydrolysis of formylthiocholine using heavy atom kinetic isotope effects. AB - Heavy atom kinetic isotope effects (KIEs) were determined for the butyrylcholinesterase-catalyzed hydrolysis of formylthiocholine (FTC). The leaving-S, carbonyl-C, and carbonyl-O KIEs are (34)k=0.994+/-0.004, (13)k=1.0148+/-0.0007, and (18)k=0.999+/-0.002, respectively. The observed KIEs support a mechanism for both acylation and deacylation where the steps up to and including the formation of the tetrahedral intermediate are at least partially rate determining. These results, in contrast to previous studies with acetylthiocholine, suggest that the decomposition of a tetrahedral intermediate is not rate-determining for FTC hydrolysis. Structural differences between the two substrates are likely responsible for the observed mechanism change with FTC. PMID- 26874344 TI - Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast alpha glucosidase. AB - Inhibition of alpha-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[2,3-c] pyrazoles (1-35) were synthesized and evaluated for their alpha-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast alpha glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (Ki=9.75+/-0.07, 46+/-0.0001, and 69.16+/-0.01MUM, respectively), compound 22 is a competitive inhibitor (Ki=190+/ 0.016MUM), while 33 was an uncompetitive inhibitor (Ki=45+/-0.0014MUM) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of alpha-glucosidase enzyme for further investigation as anti-diabetic agents. PMID- 26874345 TI - Synthesis and antiproliferative activity of benzophenone tagged pyridine analogues towards activation of caspase activated DNase mediated nuclear fragmentation in Dalton's lymphoma. AB - A series of benzophenones possessing pyridine nucleus 8a-l were synthesized by multistep reaction sequence and evaluated for antiproliferative activity against DLA cells by in vitro and in vivo studies. The results suggested that, compounds 8b with fluoro group and 8e with chloro substituent at the benzoyl ring of benzophenone scaffold as well as pyridine ring with hydroxy group exhibited significant activity. Further investigation in mouse model suggests that compounds 8b and 8e have the potency to activate caspase activated DNase (endonuclease) which is responsible for DNA fragmentation, a primary hallmark of apoptosis and thereby inhibits the Dalton's lymphoma ascites tumour growth. PMID- 26874346 TI - The Challenges of Applying Massively Parallel Sequencing to Newborn Screening for Cystic Fibrosis. AB - This Commentary highlights the article by Lefterova et al that describes newborn screening of cystic fibrosis using massively parallel sequencing. PMID- 26874347 TI - Three-stage Laparoscopic Ileal Pouch-anal Anastomosis Is the Best Approach for High-risk Patients with Inflammatory Bowel Disease: An Analysis of 185 Consecutive Patients. AB - BACKGROUND: There are very few studies and no consensus concerning the choice between two- and three-stage ileal pouch-anal anastomosis [IPAA] in inflammatory bowel diseases [IBD]. This study aimed to compare operative results between both surgical procedures. METHODS: Only patients who underwent a laparoscopic IPAA for IBD were included. They were divided into two groups: two-stage [IPAA and stoma closure] [Group A] and three-stage IPAA [subtotal colectomy, IPAA, stoma closure] [Group B]. RESULTS: From 2000 to 2015, 185 patients (107 men, median age of 42 [range, 15-78] years) were divided into Groups A [n = 82] and B [n = 103]. Patients in Group B were younger than in Group A (39 [15-78] vs 43 [16-74] years; p = 0.019), presented more frequently with Crohn's disease [16% vs 5%; p < 0.04], and were more frequently operated in emergency for acute colitis [37% vs 1%; p < 0.0001]. Cumulative operative time and length of stay were significantly longer in Group B (580 [300-900] min, and 19 [13-60] days) than in Group A (290 [145 490] min and 10 [7-47] days; p < 0.0001). Cumulative postoperative morbidity, delay for stoma closure, and function were similar between the two groups. Long term morbidity was similar between Group A [13%] and Group B [21%; p = 0.18]. CONCLUSIONS: Our study suggested that postoperative morbidity was similar between two- and three-stage laparoscopic IPAA. It suggested that the three-stage procedure is probably safer for high-risk patients [ie in acute colitis]. PMID- 26874348 TI - Higher Adalimumab Drug Levels Are Associated with Mucosal Healing in Patients with Crohn's Disease. PMID- 26874349 TI - Swallowing anti-TNFalpha in Ulcerative Colitis: Potentially More Gain Than Pain. PMID- 26874350 TI - Transportome Profiling Identifies Profound Alterations in Crohn's Disease Partially Restored by Commensal Bacteria. AB - BACKGROUND AND AIMS: Several transport alterations have been described in intestinal inflammatory diseases. This is relevant because the primary function of the intestine is nutrient and mineral absorption. However, analysis of the transportome as a whole and the effect of commensal bacteria on it have not been addressed so far. METHODS: Five healthy and 6 Crohn's disease (CD) samples were hybridized to human HT-12 V4 Illumina GeneChip. Results were validated by reverse transcription-polymerase chain reaction (RT-PCR) analysis and with additional array data. Organ culture assays were performed from mucosa ileal wall specimens collected at surgery. Samples were incubated with or without commensal bacteria for 4 hours. Finally, RNA was isolated for microarray processing. RESULTS: The analysis of CD versus healthy ileal mucosa demonstrated upregulation of previously described genes involved in immunity and the inflammatory response in this disease. Interestingly, whole transcriptional analysis revealed profound alterations in the transportome profile. Sixty-two solute carrier (SLC) transporters displayed different expression patterns, most of them being downregulated. Changes were confirmed by RT-PCR in a randomly chosen subset of SLCs. A large number of amino acid transporters and most members of the enteric purinome were found to be altered. Most of these proteins were found at the apical membrane of the enterocyte, which could impair both amino acid absorption and purinergic signalling. Treatment of ileum specimen explants with commensal bacteria restored almost all CD transportome alterations. CONCLUSIONS: These results describe the altered transportome profile in CD and open the possibility of restoring transportome complications with commensal bacteria. PMID- 26874351 TI - Faecal Lactoferrin, Calprotectin, PMN-elastase, CRP, and White Blood Cell Count as Indicators for Mucosal Healing and Clinical Course of Disease in Patients with Mild to Moderate Ulcerative Colitis: Post Hoc Analysis of a Prospective Clinical Trial. AB - OBJECTIVES: We evaluated the performance of blood and faecal biomarkers for differentiating between endoscopic inflammation and mucosal healing, and clinically active disease and sustained clinical remission, and determined the predictive value for a flare in patients with ulcerative colitis [UC]. METHODS: Clinical Activity Index [CAI], faecal lactoferrin [FLA], calprotectin [CAL], PMN elastase [PMN-e], C-reactive protein [CRP], white blood cells [WBC], Endoscopic Index [EI], and UC-Disease Activity Index [DAI] were determined repeatedly during 12 months and at acute flares. RESULTS: Of 91 patients [45 female; mean age 48.1+/-13.4 years] entering in remission, 42 [46%] patients developed a clinical flare. A total of 529 CAI and 179 EI assessments were performed. Median levels for active disease confirmed by EI [n = 35] vs clinical remission with endoscopic inflammation [n = 37] vs mucosal healing [n = 107] for FLA were 44/37/4 ug/g, CAL 25/20/10 ug/g [both p < 0.0001], PMN-e 0.06/0.03/0.02 ug/g, CRP 0.7/0.2/0.2mg/dl [both p < 0.001], and WBC 7.0/6.5/6.4/nl [p = 0.1]. There was no difference for any of the markers for defining mucosal healing by EI = 0 vs EI = 1 with the exception of PMN-e [p = 0.03], where the difference was very small and with questionable clinical relevance. Using manufacturers' cut-offs, only FLA at baseline was associated with a significant higher relative risk [RR] of flaring [RR 1.69; p = 0.018]. Using optimised cut-offs, CAL, PMN-e, and CRP were also predictive of a flare. CONCLUSIONS: Faecal biomarkers FLA, CAL, and PMN-e were able to distinguish between UC patients with mucosal healing from clinical remission and mild disease, showed significant correlations with endoscopy, and were predictive of a flare. PMID- 26874352 TI - Increased Risk for Ophthalmic Complications in Patients with a History of Preterm Delivery. AB - Objective Spontaneous preterm deliveries (PTDs) have been consistently associated with maternal vascular complications. We aimed to investigate an association between PTD and subsequent maternal ophthalmic morbidity. Study Design In this population-based cohort study, we included all singleton deliveries occurring between 1988 and 2013. We excluded women with known ophthalmic disease. The exposure was at least one pregnancy with PTD. Outcomes included different maternal ophthalmic morbidity. The cumulative incidence and adjusted hazard ratios were assessed using a Kaplan-Meier survival curve and Cox hazards models. Results Of the 105,018 patients included, 17,600 (16.7%) delivered preterm. Patients with a history of PTD (both induced and spontaneous) had higher rates of ophthalmic complications (odds ratio [OR]: 2.12; confidence interval [CI]: 1.6 2.7; p < 0.001), specifically diabetic retinopathy and glaucoma (OR: 4.79 and 2.48, respectively). A linear association was found between the number of previous PTDs and ophthalmic complications (0.2% for no PTD; 0.4% for one PTD; 0.6% for two or more PTDs; p < 0.001) and for early and late PTD (p < 0.001). A Cox model revealed an independent association between PTD and ophthalmic complications (adjusted hazard ratio: 2.2; 95% CI: 1.6-2.9). Conclusion A history of PTD is an independent risk factor for ophthalmic morbidity. PMID- 26874353 TI - The understanding of circular RNAs as special triggers in carcinogenesis. AB - Circular RNAs (circRNAs) are a large type of noncoding RNAs characterized by their circular shape resulting from covalently closed continuous loops. They are known to regulate gene expression in mammals. These tissue-specific transcripts are largely generated from exonic or intronic sequences of their host genes. Although several models of circRNA biogenesis have been proposed, the understanding of their origin is far from complete. Unlike other noncoding RNAs, circRNAs are widely expressed, highly conserved and stable in cytoplasm, which confer special functionalities to them. They are known to serve as microRNA (miRNA) sponges, regulators of alternative splicing, transcription factors and encode for proteins. The expression of circRNAs is associated with several pathological states and may potentially serve as novel diagnostic or predictive biomarkers. CircRNAs are known to regulate the expression of numerous cancer related miRNAs. The circRNA-miRNA-mRNA axis is a known regulatory pattern of several cancer-associated pathways, with both agonist and antagonist effects on carcinogenesis. In consideration of their potential clinical relevance, circRNAs are at the center of ongoing research initiatives on cancer prevention and treatment. In this review, we discuss the current understanding of circRNAs and the prospects for their potential clinical application in the management of cancer patients. PMID- 26874354 TI - Unit cohesion, traumatic exposure and mental health of military personnel. AB - BACKGROUND: The benefit of military unit cohesion to morale and psychological resilience is well established. But it remains unclear whether unit cohesion modifies the association between deployment-related traumatic exposure and mental health problems. AIMS: To examine the association between unit cohesion, traumatic exposure and poor mental health [symptoms of post-traumatic stress disorder (PTSD), psychological distress and alcohol dependency] and assess whether the relationship between traumatic exposure and poor mental health differs by level of unit cohesion. METHODS: A self-reported cross-sectional survey of Australian military personnel deployed to Iraq or Afghanistan between 2001 and 2009. RESULTS: Among 11411 participants, those with low levels of unit cohesion had higher odds of PTSD symptoms [aOR (95% CI): 2.54 (1.88, 3.42)], very high psychological distress [aOR (95% CI): 4.28 (3.04, 6.02)] and a high level of alcohol problems [aOR (95% CI): 1.71 (1.32, 2.22)] compared with those reporting high unit cohesion on deployment. Higher exposure to traumatic events on deployment was associated with greater risk of PTSD symptoms, very high levels of psychological distress and high levels of alcohol problems in this cohort. However, there was no evidence of a statistically significant interaction between unit cohesion and traumatic exposures in influencing poor mental health. CONCLUSIONS: Our findings suggest that both unit cohesion and traumatic exposure are independently associated with poor mental health. Efforts to improve military unit cohesion may help to improve the mental health resilience of military personnel, regardless of their level of traumatic exposure. PMID- 26874356 TI - Life history theory and breast cancer risk: methodological and theoretical challenges: Response to "Is estrogen receptor negative breast cancer risk associated with a fast life history strategy?". AB - In a meta-analysis published by myself and co-authors, we report differences in the life history risk factors for estrogen receptor negative (ER-) and estrogen receptor positive (ER+) breast cancers. Our meta-analysis did not find the association of ER- breast cancer risk with fast life history characteristics that Hidaka and Boddy suggest in their response to our article. There are a number of possible explanations for the differences between their conclusions and the conclusions we drew from our meta-analysis, including limitations of our meta analysis and methodological challenges in measuring and categorizing estrogen receptor status. These challenges, along with the association of ER+ breast cancer with slow life history characteristics, may make it challenging to find a clear signal of ER- breast cancer with fast life history characteristics, even if that relationship does exist. The contradictory results regarding breast cancer risk and life history characteristics illustrate a more general challenge in evolutionary medicine: often different sub-theories in evolutionary biology make contradictory predictions about disease risk. In this case, life history models predict that breast cancer risk should increase with faster life history characteristics, while the evolutionary mismatch hypothesis predicts that breast cancer risk should increase with delayed reproduction. Whether life history tradeoffs contribute to ER- breast cancer is still an open question, but current models and several lines of evidence suggest that it is a possibility. PMID- 26874357 TI - The proteolytic activity of pregnancy-associated plasma protein-A is potentially regulated by stanniocalcin-1 and -2 during human ovarian follicle development. AB - STUDY QUESTION: Is the proteolytic activity of pregnancy-associated plasma protein-A (PAPP-A) regulated by the stanniocalcins (STC1 and STC2) during human follicle maturation? SUMMARY ANSWER: The STCs and PAPP-A show similar expression by immunohistochemistry in developing follicles, and regulation of PAPP-A proteolytic activity is suggested by the identification of inhibited protein complexes between PAPP-A and STC1 or STC2 in human follicular fluid (FF). WHAT IS KNOWN ALREADY: The insulin-like growth factor (IGF)-regulating proteinase PAPP-A is secreted by the granulosa cells of estrogen-dominant follicles and is involved in follicle growth. STC1 and STC2 have recently been identified as novel PAPP-A inhibitors, and their expression in non-human mammalian ovaries has previously been observed. STUDY DESIGN, SIZE, DURATION: The proteolytic activity of PAPP-A in human follicular fluid was assessed, and the interaction between PAPP-A and the STCs in human ovarian tissues and follicular fluid was analyzed using immunoassays. From 21 women, matched pairs of follicular fluid were obtained from one follicle just prior to final maturation of follicles with human chorionic gonadotrophin (hCG), and from another follicle in connection with oocyte aspiration after hCG treatment. Ovarian tissues were obtained from women having one ovary removed for fertility preservation by cryopreservation prior to gonadotoxic treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The concentration and activity of PAPP-A were determined in all samples of follicular fluid. Furthermore, to investigate PAPP-A regulation during follicle development, immunohistochemical staining of PAPP-A, STC1, and STC2 was performed on pre antral and antral human follicles. To attempt the demonstration of native complexes between PAPP-A and the STCs, immunoprecipitation from a pool of human follicular fluid was performed. MAIN RESULTS AND THE ROLE OF CHANCE: The concentration of PAPP-A antigen in follicular fluid increased upon stimulation of ovulation with hCG (P < 0.02), but at the same time, PAPP-A activity was decreased. PAPP-A, STC1, and STC2 were localized together in primordial, late primary, and antral follicles, indicating that complex formation is possible in ovarian tissue. Covalent PAPP-A:STC2 and non-covalent PAPP-A:STC1 complexes were immunoprecipitated from follicular fluid, documenting for the first time native inhibited complexes between PAPP-A and the STCs. LIMITATIONS, REASONS FOR CAUTION: We have demonstrated the presence of native complexes between PAPP-A and the STCs in the human ovary, indicating STC-mediated PAPP-A proteolytic inhibition. Further investigation is required to extend this principle to other tissues. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that the STCs contribute to PAPP-A regulation during folliculogenesis and support a general model in which STC1 and STC2 are regulators of mammalian IGF activity through inhibition of PAPP-A. We suggest that future functional studies take both PAPP-A and the STCs into consideration. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the Novo Nordisk Foundation, and the Danish Council for Independent Research. No competing interests declared. PMID- 26874355 TI - CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm. AB - CD4(+)T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4(+)T-cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID- 26874358 TI - Vaginal estradiol use and the risk for cardiovascular mortality. AB - STUDY QUESTION: Does the use of post-menopausal vaginal estradiol (VE) affect the mortality risk for coronary heart disease (CHD) and stroke. SUMMARY ANSWER: The use of VE reduces the risk for cardiovascular mortality. WHAT IS KNOWN ALREADY: A growing number of women use VE for post-menopausal genitourinary symptoms. Although this therapy is intended to have only local effects, estrogen is absorbed into the blood circulation and thus VE use may also have systemic effects. STUDY DESIGN, SIZE, DURATION: We studied a nationwide cohort in Finland 1994-2009 during which post-menopausal women (n = 195 756) initiated the use of VE (age [mean +/- SD] 65.7 +/- 10.9 years). Follow-up data gathered 1.4 million women-years and we assessed the mortality risk due to CHD (n= 9656) or stroke (n = 4294). PARTICIPANTS/MATERIALS, SETTING, METHODS: The mortality risk in VE users was compared with that in the age-matched background population (standardized mortality ratio; [SMR]; 95% confidence interval) and related to various durations of exposure to VE (1 to <=3, >3 to <=5, >5 to <=10 and >10 years). MAIN RESULTS AND THE ROLE OF CHANCE: The use of VE was accompanied by decreases in the risk for CHD and stroke death. The risk reduction for CHD death was highest for >3 to <=5 years exposure (SMR 0.64; 0.57-0.70) and for stroke for >5 to <=10 years exposure (SMR 0.64; 0.57-0.72). The risk reductions for both CHD and stroke mortality were detected in all age groups with the highest risk reduction being in women aged 50-59 years (SMR 0.43; 0.19-0.88 and SMR 0.21; 0.06-0.58, respectively). LIMITATIONS, REASONS FOR CAUTION: Our series lack a placebo arm and thus, may harbor a healthy woman bias. Moreover, data on clinical variables such as weight, smoking, blood pressure and family background were unobtainable for this study. Women using both VE and systemic hormone therapy (HT) were included in the comparator background population. This should not cause any significant error because the proportion of women using VE or other HT was modest (<10% in age-matched population) and because the use of systemic HT also reduces death risks in the same population. Our data cannot be directly applied for local regimens containing conjugated equine estrogens, because they are absorbed differently and may show effects that differ from those of estradiol. WIDER IMPLICATIONS OF THE FINDINGS: In 1000 women using VE for up to 10 years, a maximum of 24 fewer CHD deaths and 18 fewer stroke deaths is likely to occur. STUDY FUNDING/COMPETING INTERESTS: This work was supported by unrestricted grants from the Paivikki and Sakari Sohlberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, Finska Lakaresallskapet, the Orion Farmos Research Foundation, the Paavo Nurmi Foundation and a special governmental grant for health sciences research. The funding sources had no role in the study design, data handling or manuscript preparation. EPID Research is a company that performs financially supported studies for several pharmaceutical companies. Dr Korhonen, Dr Hoti and MSc Vattulainen, employed by Epid Research, report financial activities from several other pharmaceutical companies outside the submitted work. Dr Mikkola has been a speaker and/or received consulting fees from Mylan and Novo Nordisk. Dr Tuomikoski has been a speaker and/or received consulting fees from Orion and Mylan. The remaining authors report no conflict of interest. PMID- 26874359 TI - Single-cell transcriptome analysis of endometrial tissue. AB - STUDY QUESTION: How can we study the full transcriptome of endometrial stromal and epithelial cells at the single-cell level? SUMMARY ANSWER: By compiling and developing novel analytical tools for biopsy, tissue cryopreservation and disaggregation, single-cell sorting, library preparation, RNA sequencing (RNA seq) and statistical data analysis. WHAT IS KNOWN ALREADY: Although single-cell transcriptome analyses from various biopsied tissues have been published recently, corresponding protocols for human endometrium have not been described. STUDY DESIGN, SIZE, DURATION: The frozen-thawed endometrial biopsies were fluorescence-activated cell sorted (FACS) to distinguish CD13-positive stromal and CD9-positive epithelial cells and single-cell transcriptome analysis performed from biopsied tissues without culturing the cells. We studied gene transcription, applying a modern and efficient RNA-seq protocol. In parallel, endometrial stromal cells were cultured and global expression profiles were compared with uncultured cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: For method validation, we used two endometrial biopsies, one from mid-secretory phase (Day 21, LH+8) and another from late-secretory phase (Day 25). The samples underwent single-cell FACS sorting, single-cell RNA-seq library preparation and Illumina sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: Here we present a complete pipeline for single-cell gene-expression studies, from clinical sampling to statistical data analysis. Tissue manipulation, starting from disaggregation and cell-type-specific labelling and ending with single-cell automated sorting, is managed within 90 min at low temperature to minimize changes in the gene expression profile. The single living stromal and epithelial cells were sorted using CD13- and CD9-specific antibodies, respectively. Of the 8622 detected genes, 2661 were more active in cultured stromal cells than in biopsy cells. In the comparison of biopsy versus cultured cells, 5603 commonly expressed genes were detected, with 241 significantly differentially expressed genes. Of these, 231 genes were up- and 10 down-regulated in cultured cells, respectively. In addition, we performed a gene ontology analysis of the differentially expressed genes and found that these genes are mainly related to cell cycle, translational processes and metabolism. LIMITATIONS, REASONS FOR CAUTION: Although CD9-positive single epithelial cells sorting was successfully established in our laboratory, the amount of transcriptome data per individual epithelial cell was low, complicating further analysis. This step most likely failed due to the high dose of RNases that are released by the cells' natural processes, or due to rapid turnaround time or the apoptotic conditions in freezing- or single-cell solutions. Since only the cells from the late-secretory phase were subject to more focused analysis, further studies including larger sample size from the different time-points of the natural menstrual cycle are needed. The methodology also needs further optimization to examine different cell types at high quality. WIDER IMPLICATIONS OF THE FINDINGS: The symbiosis between clinical biopsy and the sophisticated laboratory and bioinformatic protocols described here brings together clinical diagnostic needs and modern laboratory and bioinformatic solutions, enabling us to implement a precise analytical toolbox for studying the endometrial tissue even at the single-cell level. PMID- 26874360 TI - Elevated phosphatase of regenerating liver 3 (PRL-3) promotes cytoskeleton reorganization, cell migration and invasion in endometrial stromal cells from endometrioma. AB - STUDY QUESTION: Is phosphatase of regenerating liver-3 (PRL-3) associated with increased motility of endometriotic cells from endometrioma? SUMMARY ANSWER: Elevated PRL-3 promotes cytoskeleton reorganization, cell migration and invasion of endometrial stromal cells (ESCs) from endometrioma. WHAT IS KNOWN ALREADY: Overexpression of PRL-3 is associated with cancer cell migration, invasion and metastatic phenotype. STUDY DESIGN, SIZE, DURATION: Primary human ESCs were isolated from eutopic endometrium of women without endometriosis (EuCo, n = 10), with histologically proven endometrioma (EuEM, n = 19) and from the cyst wall of ovarian endometriosis (OvEM, n = 26). PARTICIPANTS/MATERIALS, SETTING, METHODS: The expression of PRL-3 in ESCs derived from EuCo, EuEM and OvEM at different phases of menstrual cycle were compared. The protein and mRNA levels of PRL-3 were examined by western blot and RT-qPCR, respectively. ESCs from OvEM were transfected with/without short hairpin RNA (shRNA) or small interfering RNA (siRNA). Additionally, a plasmid-mediated delivery system was used to achieve PRL 3 overexpression in ESCs from EuEM. The cellular distribution of F-actin and alpha-tubulin were examined by immunocytochemistry. Cell motility was evaluated by a transwell migration/invasion assay. MAIN RESULTS AND THE ROLE OF CHANCE: The protein and mRNA levels of PRL-3 are significantly elevated in ESCs from OvEM compared with EuCo and EuEM. The expression of PRL-3 was not altered between proliferative phase and secretory phase in ESCs from all groups. Knockdown of PRL 3 significantly modified the distribution of F-actin and alpha-tubulin cytoskeleton, inhibited cell migration and invasion. Endogenous inhibition of PRL 3 attenuated the expression of Ras homolog gene family members A and C (RhoA, RhoC), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) and matrix metalloproteinase (MMP) 9, but not MMP2 in ESCs from OvEM. Additionally, overexpression of PRL-3 in ESCs from EuEM up-regulates cell migration and invasion, and increases the expression of RhoA, RhoC, ROCK1 and MMP9. LIMITATIONS, REASONS FOR CAUTION: Lack of in vivo animal studies is the major limitation of our report. Our results should be further confirmed in a larger cohort of patients and extended to include eutopic and ectopic endometrium from patients with peritoneal endometriosis at different stages of the disease. WIDER IMPLICATIONS OF THE FINDINGS: Our study describes that elevated expression of PRL 3 contributes to the cell motility of ESCs from endometrioma. The results emphasize the importance of metastatic-related factor PRL-3 in the pathogenesis of endometrioma. STUDY FUNDING/COMPETING INTEREST: This work was supported by National Natural Science Foundation of China (No. 81170546) and Zhejiang Medicine Science and Technology Projects (No. Y13H040003). The authors declare no conflict of interest. PMID- 26874361 TI - Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome. AB - STUDY QUESTION: What are the prevalence and the outcomes of spontaneous pregnancies (SP) in a large cohort of French women with Turner syndrome (TS)? SUMMARY ANSWER: Amongst 480 women with TS, 27 women (5.6%) had a total of 52 SP, with 30 full-term deliveries for 18 women. WHAT IS KNOWN ALREADY: Primary ovarian insufficiency is a classic feature of TS. So far, few studies have evaluated the rate of SP in these patients. STUDY DESIGN, SIZE, DURATION: The French Ministry of Health set up a National Reference Centre for Rare Growth Disorders (CRMERC), including TS. We studied a cohort of adult TS patients from seven endocrine units (Saint-Antoine, Pitie-Salpetriere, Bicetre, Lyon, Marseille, Brest, Reims Hospitals) belonging to this centre, between January 1999 and January 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 480 adult patients with TS were included. The patients' clinical characteristics, karyotypes and reproductive histories had been collected, after informed consent, in a web database called CEMARA. Our reference population was issued from a database belonging to the French Health Ministry, collecting pregnancy outcomes in the French general population. In order to find predictive characteristics of SP, TS with spontaneous pregnancies were compared with non-pregnant TS patients from our cohort. MAIN RESULTS AND THE ROLE OF CHANCE: There were 27 patients (5.6%) who had a total of 52 SP. The two predictive factors which correlated with occurrence of a SP were spontaneous menarche and mosaic karyotype. The median delay to conception was 6 months (range 0-84). Miscarriage occurred in 16 pregnancies, 30.8% versus 15% in the general French population (P < 0.01). The remaining pregnancy outcomes were legal abortion (n = 2), medical interruption (n = 3), intrauterine fetal death (n = 1) and delivery at term (n = 30). Caesarean section rates were higher than in the general population, respectively 46.7% versus 21% (P < 0.001). Pregnancy-induced hypertensive disorders (PHDs) occurred in four cases (13.3%), including two cases of mild pre-eclampsia (6.7%). Neither aortic root dilatation nor aortic dissection were observed. The median birthweight was 3030 g (range 2020-3460). Two cases of TS were identified in the 17 daughters issued from this cohort. LIMITATIONS, REASONS FOR CAUTION: It would have been interesting to evaluate AMH levels and SP occurrence, as a predictive factor. Unfortunately, hormonal measurements were missing for some patients. Prospective studies are necessary to display prognostic values of AMH for SP and thus better target fertility preservation programmes in TS patients. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that pregnancy outcomes in SPs are more favourable than those after oocyte donation in TS patients. However, the risk of fetal chromosomal abnormalities remains high. Our study will be useful in order to give patients with TS, their families, paediatricians and physicians involved in reproduction, better counselling concerning their fertility. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the Association pour la recherche Claude Bernard, Paris France All authors claim no competing interests. TRIAL REGISTRATION NUMBER: NA. PMID- 26874362 TI - Expanding the Nomological Net of the Pathological Narcissism Inventory: German Validation and Extension in a Clinical Inpatient Sample. AB - The Pathological Narcissism Inventory (PNI) is a multidimensional measure for assessing grandiose and vulnerable features in narcissistic pathology. The aim of the present research was to construct and validate a German translation of the PNI and to provide further information on the PNI's nomological net. Findings from a first study confirm the psychometric soundness of the PNI and replicate its seven-factor first-order structure. A second-order structure was also supported but with several equivalent models. A second study investigating associations with a broad range of measures ( DSM Axis I and II constructs, emotions, personality traits, interpersonal and dysfunctional behaviors, and well being) supported the concurrent validity of the PNI. Discriminant validity with the Narcissistic Personality Inventory was also shown. Finally, in a third study an extension in a clinical inpatient sample provided further evidence that the PNI is a useful tool to assess the more pathological end of narcissism. PMID- 26874363 TI - Experimental study on the effect of oral meloxicam administration in sows on pre weaning mortality and growth and immunoglobulin G transfer to piglets. AB - Parturation is an intrinsically risky and painful process for both the sow and the piglets that can cause welfare and economic problems. Non-steroidal anti inflammatory drugs (NSAIDs) have been demonstrated to partially alleviate inflammation and pain after farrowing in sows. NSAIDs effects on piglet mortality and performance show discrepancies and no previous studies have investigated the underlying mechanism. The effects of oral meloxicam treatment to sows on immunoglobulin G (IgG) transfer to piglets around farrowing were investigated. A total of 30 multiparous sows were randomly treated with either oral meloxicam or a mock administration as control group. Treatment was administered as soon as possible at the beginning of the farrowing. A total of 325 piglets were individually weighed at farrowing (day 0) and at weaning (day +21) and piglet mortality was registered during lactation. Four piglets per sow (two piglets suckling from anterior teats and two piglets suckling from posterior teats) were selected for blood sampling at day +1, day +2 and day +20 for IgG analyses. Oral meloxicam treatment to sows significantly increased weight at weaning (mean+/-SE: 6563+/-86.3g from oral meloxicam group and 6145+/-103.2g from control group; P=0.0017) and ADG (mean+/-SE: 236+/-3.4g/day from oral meloxicam group and 217+/ 4.5g/day from control group; P<0.001) during lactation, but failed to reduce piglet mortality during lactation (6.7% from oral meloxicam group and 6.8% from control group; P=0.89). IgG levels in piglets from the sows treated with oral meloxicam were significantly higher than the control group at day +1 (mean; median [95% CI] for median=31.9; 31.7 [29.6-33.6] vs. 27.9; 26.8 [25.9-28.3] mg/ml, P=0.0013) and day +2 (27.6; 27.0 [24.8-29.6] vs. 24.5; 24.2 [22.1-25.3] mg/ml, P=0.01). However, at day +20, IgG level in piglet serum was not significantly affected by the treatment (7.6; 7.6 [6.7-8.4] vs. 7.1; 6.9 [6.4 7.3] mg/ml, P=0.59). The administration of meloxicam orally at the beginning of the farrowing in multiparous sows increased the concentration of IgG in serum of piglets and enhanced their pre-weaning growth. Future research is warranted to clearly identify the proximate mechanism behind IgG effect. PMID- 26874364 TI - A case-control study to estimate the effects of acute clinical infection with the Schmallenberg virus on milk yield, fertility and veterinary costs in Swiss dairy herds. AB - Schmallenberg virus (SBV) was first detected in Switzerland in July 2012 and many Swiss dairy farmers reported acute clinical signs in dairy cattle during the spread of the virus until December 2012. The objectives of the present study were to investigate the effects of an acute infection with SBV on milk yield, fertility and veterinary costs in dairy farms with clinical signs of SBV infection (case farms), and to compare those farms to a matched control group of dairy farms in which cattle did not show clinical signs of SBV infection. Herd size was significantly (p<0.001) larger in case farms (33 cows, n=77) than in control farms (25 cows, n=84). Within case herds, 14.8% (median) of the cows showed acute clinical signs. Managers from case farms indicated to have observed a higher abortion rate during the year with SBV (6.5%) than in the previous year (3.7%). Analysis of fertility parameters based on veterinary bills and data from the breeding associations showed no significant differences between case and control farms. The general veterinary costs per cow from July to December 2012 were significantly higher (p=0.02) in case (CHF 19.80; EUR 16.50) than in control farms (CHF 15.90; EUR 13.25). No differences in milk yield were found between groups, but there was a significant decrease in milk production in case farms in the second half year in 2012 compared to the same period in 2011 (p<0.001) and 2013 (p=0.009). The average daily milk yield per cow (both groups together) was +0.73kg higher (p=0.03) in the second half year 2011 and +0.52kg (p=0.12) in the second half year 2013 compared to the same half year 2012. Fifty-seven percent of the cows with acute clinical signs (n=461) were treated by a veterinarian. The average calculated loss after SBV infection for a standardized farm was CHF 1606 (EUR 1338), which can be considered as low at the national level, but the losses were subject to great fluctuations between farms, so that individual farms could have very high losses (>CHF 10,000, EUR 8333). PMID- 26874365 TI - Analysis of Outcomes Using Low-Dose and Early Administration of Recombinant Activated Factor VII in Cardiac Surgery. AB - BACKGROUND: Although not currently approved for postoperative cardiac surgical bleeding, recombinant activated factor VII (rFVIIa) has been used for this purpose. This study sought to analyze outcomes in patients who had cardiac surgical bleeding and received low-dose and early administration of rFVIIa versus outcomes in patients who had cardiac surgical bleeding and did not receive rFVIIa. METHODS: Fifty-one patients receiving rFVIIa were matched, using The Society of Thoracic Surgeons morbidity and mortality scores, with 51 patients who underwent cardiac surgical procedures and met criteria for surgical bleeding. Primary outcomes were ventilator hours and intensive care unit length of stay. Secondary outcomes included 30-day mortality, acute kidney injury, postoperative hospital length of stay, thromboembolic events, postoperative pneumonia, and sternal wound infections. Reoperations for bleeding were analyzed for each group to assess for achievement of hemostasis. RESULTS: The median total dose of rFVIIa was 12 mcg/kg. rFVIIa was given as the first and only treatment for bleeding in 7 of 51 (13%) patients, whereas 13 of 51 patients receiving rFVIIa (25%) also received up to 1 unit of any blood product. Patients who received rFVIIa had increased duration of mechanical ventilation (p = 0.002) and increased length of stay in the intensive care unit (p = 0.02). There were no differences in hospital length of stay, 30-day mortality, acute kidney injury, postoperative pneumonia, sternal wound infections, postoperative thromboembolic events, or rate of reoperations for bleeding. CONCLUSIONS: Low-dose and early administration of rFVIIa (median total dose 12 mcg/kg) for cardiac surgical bleeding shows potential in achieving hemostasis without increased risk of thromboembolism or acute kidney injury. PMID- 26874367 TI - Vitamin D3 treatment of vitamin D-insufficient asthmatic patients does not alter immune cell function. PMID- 26874366 TI - Prenatal, perinatal, and childhood vitamin D exposure and their association with childhood allergic rhinitis and allergic sensitization. AB - BACKGROUND: The role of early-life vitamin D in childhood allergy is controversial. OBJECTIVE: We sought to assess vitamin D exposure in early life by multiple modalities and ascertain its association with childhood allergic rhinitis and allergic sensitization. METHODS: One thousand two hundred forty eight mother-child pairs from a US prebirth cohort unselected for any disease were studied. Vitamin D exposure was assessed by measures of maternal intake during the first and second trimesters of pregnancy and serum 25-hydroxyvitamin D (25[OH]D) levels in mothers during pregnancy, cord blood, and children at school age (median age, 7.7 years; interquartile range, 1.0 years). Tests for associations between vitamin D exposure with ever allergic rhinitis, serum total IgE level, and allergen sensitization at school age were conducted. RESULTS: The correlations between maternal intake of vitamin D during pregnancy and serum 25(OH)D levels in pregnant mothers, cord blood, and children at school age were weak to moderate (r = -0.03 to 0.53). Each 100 IU/d of food-based vitamin D intake during the first and second trimesters (equivalent to the amount of vitamin D in an 8-ounce serving of milk) was associated with 21% and 20% reduced odds of ever allergic rhinitis at school age (odds ratios of 0.79 [95% CI, 0.67 0.92] and 0.80 [95% CI, 0.68-0.93]), respectively. There were no associations between maternal supplemental vitamin D intake or serum 25(OH)D levels at any time point with ever allergic rhinitis. There were no associations between any vitamin D exposure and serum total IgE level or allergen sensitization at school age. CONCLUSIONS: Inclusion of foods containing vitamin D in maternal diets during pregnancy may have beneficial effects on childhood allergic rhinitis. PMID- 26874368 TI - Calculating the effect of population-level implementation of the Learning Early About Peanut Allergy (LEAP) protocol to prevent peanut allergy. PMID- 26874369 TI - Self-assembly and sequence length dependence on nanofibrils of polyglutamine peptides. AB - Huntington's disease (HD) is recognized as a currently incurable, inherited neurodegenerative disorder caused by the accumulation of misfolded polyglutamine (polyQ) peptide aggregates in neuronal cells. Yet, the mechanism by which newly formed polyQ chains interact and assemble into toxic oligomeric structures remains a critical, unresolved issue. In order to shed further light on the matter, our group elected to investigate the folding of polyQ peptides - examining glutamine repeat lengths ranging from 3 to 44 residues. To characterize these aggregates we employed a diverse array of technologies, including: nuclear magnetic resonance; circular dichroism; Fourier transform infrared spectroscopy; fluorescence resonance energy transfer (FRET), and atomic force microscopy. The data we obtained suggest that an increase in the number of glutamine repeats above 14 residues results in disordered loop structures, with different repeat lengths demonstrating unique folding characteristics. This differential folding manifests in the formation of distinct nano-sized fibrils, and on this basis, we postulate the idea of 14 polyQ repeats representing a critical loop length for neurotoxicity - a property that we hope may prove amenable to future therapeutic intervention. Furthermore, FRET measurements on aged assemblages indicate an increase in the end-to-end distance of the peptide with time, most probably due to the intermixing of individual peptide strands within the nanofibril. Further insight into this apparent time-dependent reorganization of aggregated polyQ peptides may influence future disease modeling of polyQ-related proteinopathies, in addition to directing novel clinical innovations. PMID- 26874370 TI - Bony contact area and displacement of the temporomandibular joint after high oblique and bilateral sagittal split osteotomy: a computer-simulated comparison. AB - The most common way to move the mandible during orthognathic surgery is by bilateral sagittal split osteotomy (BSSO). The high-oblique sagittal split osteotomy (HSSO) is an alternative, although its use is limited by potential complications, mainly to do with the position of the condyle and reduced contact with bone. The aim of this study was to find out the optimal intercondylar distance and area of contact with the surface of the bone for mandibular advancement and setback in BSSO and HSSO. Data from computed tomographic (CT) images from 40 patients were loaded into special planning software, and virtual operations done for mandibular advancement and setback at 3, 5, 8, and 10mm using BSSO and HSSO, which resulted in 640 individual mandibular displacements. The resultant area of bony contact and intercondylar distance were calculated by the software. The mean (SD) areas of contact with the bony surface after 10mm advancement for HSSO and BSSO were 193.94 (63.76) mm(2) and 967.92 (229.21) mm(2), respectively, and after 10mm setback 202.64 (62.30) mm(2) and 1108.86 (247.38) mm(2). The mean corresponding intercondylar distance after maximum advancement were 86.76 (6.40) mm and 86.59 (6.24) mm, and after maximum setback 74.90 (5.73) mm and 73.06 (6.06) mm. There were significant differences between the two for the area of contact with the surface at each displacement distance (p<0.001), but not for intercondylar distance. A larger area of bony contact can be expected at any displacement distance for BSSO, so the changes in intercondylar distance should not be considered when deciding which osteotomy to select. PMID- 26874372 TI - Computer-assisted preoperative simulation for positioning of plate fixation in Lefort I osteotomy: A case report. AB - Computed tomography images are used for three-dimensional planning in orthognathic surgery. This facilitates the actual surgery by simulating the surgical scenario. We performed a computer-assisted virtual orthognathic surgical procedure using optically scanned three-dimensional (3D) data and real computed tomography data on a personal computer. It helped maxillary bone movement and positioning and the titanium plate temporary fixation and positioning. This simulated the surgical procedure, which made the procedure easy, and we could perform precise actual surgery and could forecast the postsurgery outcome. This simulation method promises great potential in orthognathic surgery to help surgeons plan and perform operative procedures more precisely. PMID- 26874371 TI - Effect of the osmolarity change in multipurpose solutions induced by an improper contact lens case cleaning procedure. AB - PURPOSE: To determine whether variations in multipurpose disinfecting solution (MPDS) storage osmolarity from inappropriate contact lens (CL) case cleaning affect ocular surface integrity and wearer comfort. METHODS: There were twenty contact lens cases (study CLCs) in the study group. Ten were filled with ReNu Multiplus((r)) and 10 with SoloCare AquaTM (MPDS-1 and -2, respectively) and kept closed for 8h; the cases were then emptied and kept open for air-drying for 16h. This procedure was carried out every day for two months. Storage solution osmolarity was measured on days 0, 15, 30, 45 and 60. Ten subjects were then fitted with both month-old lenses stored in the study CLCs and with new lenses stored in new cases with fresh solution for 24h (control CLCs). Symptoms, tear osmolarity and percentage of subjects whose conjunctival hyperaemia and ocular surface staining scores changed were determined after 1h of wear. RESULTS: Study CLC osmolarity increased in both solutions after two months (p<0.05). For MPDS-1 there were differences in stinging between study CLCs and control CLCs after 10min of CL wear (p=0.04), and in comfort after 10 (p=0.035) and 60min wear (p=0.042). Significant (p<0.05) differences between study CLC and control CLC groups were also found for MPDS-2 in limbal hyperaemia (study: 50% change; control: 0% change) and bulbar and corneal staining (study: 80% change; control: 20% change). CONCLUSION: The stored-MPDS osmolarity increase caused by air-drying the CLCs could affect the ocular surface. This increase might reduce lens wear comfort. PMID- 26874373 TI - Burden of disease attributable to ambient fine particulate matter exposure in Taiwan. AB - BACKGROUND/PURPOSE: There is compelling epidemiological evidence that links air pollution to increased risk of mortality from cardiopulmonary disease and lung cancer. We quantified the burden of mortality attributable to ambient fine particulate matter (PM2.5) among the Taiwanese population in 2014 at the national and subnational levels. METHODS: Subnational PM2.5 exposure levels were obtained from Taiwan Air Quality Monitoring Network. Relative risks were derived from a previously developed exposure-response model. Population attributable fraction for cause-specific mortality was estimated at the county level using the estimated ambient PM2.5 concentrations and the relative risk functions. RESULTS: In 2014, PM2.5 accounted for 6282 deaths [95% confidence interval (CI), 5716 6847], from ischemic heart disease (2244 deaths; 95% CI, 2015-2473), stroke (2140 deaths; 95% CI, 1760-2520), lung cancer (1252 deaths; 95% CI, 995-1509), and chronic obstructive pulmonary disease (645 deaths; 95% CI, 418-872). Nationally, the population attributable mortality fraction of PM2.5 for the four disease causes was 18.6% (95% CI, 16.9-20.3%). Substantial geographic variation in PM2.5 attributable mortality fraction was found; the percentage of deaths attributable to PM2.5 ranged from 8.7% in Hualian County to 21.8% in Yunlin County. In terms of absolute number of deaths, New Taipei and Kaohsiung cities had the largest number of deaths associated with PM2.5 (874 and 829 deaths, respectively) among all cities and counties. CONCLUSION: Ambient PM2.5 pollution is a major mortality risk factor in Taiwan. Aggressive and multisectorial intervention strategies are urgently needed to bring down the impact of air pollution on environment and health. PMID- 26874374 TI - Scratch resistance of the ventral skin surface in four snake species (Squamata, Serpentes). AB - Snakes are limbless tetrapods highly specialized for sliding locomotion on various substrates. Their skin is constantly exposed to high friction forces, which promotes abrasion. Snake skin has material and surface specializations, presumably optimized for friction and abrasion resistance. We found that different snake species living in different habitats have different abrasion patterns and hypothesized that this correlates with specific epidermal architecture and surface topography. To test this hypothesis artificial scratches, under controlled load conditions, were created on the ventral skin material (epidermis) of four snake species adapted to different habitats: Lampropeltis getula californiae (stony and sandy soil substrates), Epicrates cenchria cenchria (trees, soil and water), Morelia viridis (trees), and Gongylophis colubrinus (burrowing in sand). Abrasion appearance on the skin surface was examined using scanning electron microscopy and white light interferometry. The material failure was different between the species, which we attribute to differences in the epidermis' response to the same abrasive challenge. We also discuss abrasion resistance mechanisms and the correlation with the different ultrastructure and surface microstructure. PMID- 26874375 TI - One year online measurements of water-soluble ions at the industrially polluted town of Nanjing, China: Sources, seasonal and diurnal variations. AB - Half-hourly mass concentrations water-soluble ions (WSIs) and PM2.5 were measured online a Rapid Collector of Fine Particles and Ion Chromatography system (RCFP IC) and FH62C14 Continuous Particulate Monitor in Nanjing from October 18, 2013 to November 17, 2014. The WSIs concentration ranged from 7.07 to 333.42 MUg m(-3) with an annual mean of 76.32 MUg m(-3). The WSIs ranked in the order of SO4(2-) > NH4(+) > NO3(-) > Cl(-) > NO2(-) > K(+) > Ca(2+) > Na(+) > Mg(2+). The PM2.5 concentration ranged from 4.00 to 400 MUg m(-3) with an annual mean of 83.58 MUg m(-3). The concentrations of WSIs varied in the order of winter (115.77 MUg m( 3)) > spring (76.10 MUg m(-3)) > autumn (63.72 MUg m(-3)) > summer (59.75 MUg m( 3)), with the highest level in January (123.99 MUg m(-3)) and lowest level in August (43.73 MUg m(-3)). Different WSIs had distinct diurnal variations. The source analysis of the WSIs in the PCA/APCS mode illustrated that the sources consisted of secondary aerosol, coal combustion, mineral dust, biomass burning, traffic emissions and sea salt. In addition, there were seasonal variations amongst the various sources. The haze formation mechanism was different in summer and winter. The winter was dominated by NH4NO3 (18.56%), (NH4)2SO4 (28.63%), NH4(+) (11.27%), SO4(2-) (18.35%) and NO3(-) (13.13%), and by NH3 (25.93%), (NH4)2SO4 (13.37%), SO4(2-) (15.74%) and NO3(-) (9.97%) in summer. Consequently, the proportions of HCl, HNO3, NH4(+), SO4(2-) and NO3(-) were much larger during haze episodes in winter, while it was dominated by NH4NO3, NH4(+), (NH4)2SO4, SO4(2-) and NO3(-) during summer haze episodes. PMID- 26874376 TI - Asymmetric mono- and dinuclear GaIII and ZnII complexes as models for purple acid phosphatases. AB - Derivatives of the known dinucleating ligands HL1 (2,6-bis{[bis(pyridin-2 ylmethyl)amino]methyl}-4-methylphenol) and H2L2 (2-{[bis(pyridin-2 ylmethyl)amino]methyl}-6-{[(2-hydroxybenzyl)(pyridine-2-ylmethyl)amino]methyl}-4 methylphenol) with two pivaloylamido hydrogen bond donor substituents, H3L3 and H3L5, have been prepared. The mono-, homo- and heterodinuclear ZnII and GaIII complexes of these ligands have been prepared and characterized. The solution equilibria are discussed on the basis of extensive NMR spectroscopic, mass spectrometric and pH-dependent UV-vis spectroscopic titrations. The phosphoester hydrolysis activity of the complexes has been studied as a function of pH and substrate concentration and analyzed using Michaelis-Menten kinetics. It emerges that the mixed metal (mixed valent) complex of the ligand with an asymmetric disposition of the hydrogen bonding substituents (H3L3) is a functional model for the mixed valent, dinuclear metallohydrolase purple acid phosphatase. This complex combines the essential structural features of the active site of PAP and is the first heterodinuclear model complex mimicking the essential function of PAPs, i.e. the hydrolysis of phosphomonoesters. PMID- 26874377 TI - A Machine Without an Owner's Manual. PMID- 26874378 TI - Oxygen Uptake Efficiency Slope and Breathing Reserve, Not Anaerobic Threshold, Discriminate Between Patients With Cardiovascular Disease Over Chronic Obstructive Pulmonary Disease. AB - OBJECTIVES: The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease. BACKGROUND: CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared. METHODS: A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after ~10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC). RESULTS: Peak VO2 was similar between the 2 principal groups (COPD 17.1 +/- 4.6 ml/min/kg; HFrEF 16.4 +/- 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide. CONCLUSIONS: Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083). PMID- 26874379 TI - Variable Contribution of Heart Failure to Quality of Life in Ambulatory Heart Failure With Reduced, Better, or Preserved Ejection Fraction. AB - OBJECTIVES: The relative contribution of heart failure (HF) compared with other medical and nonmedical factors on diminished quality of life (QOL) across subtypes with reduced, better, and preserved left ventricular ejection fraction (LVEF) in a large ambulatory HF population was evaluated. BACKGROUND: Dominant factors influencing limited QOL in patients with HF have not been investigated. METHODS: Before routine HF clinic visits, 726 patients with ambulatory HF (mean age 56 +/- 15 years, 37% women) completed a 1-page questionnaire that assessed QOL and relative contributions of HF compared with other medical and nonmedical factors to their QOL limitations. Visual analogue scales were used to assess overall QOL, breathing, and energy level. Results were compared across reduced (57%), preserved (16%) and better (improvement in LVEF >=50%) (19%) subtypes. RESULTS: Just under one-half of patients (48%) rated QOL as limited dominantly by HF, 19% rated HF and medical problems as equally limiting, 18% cited medical problems as dominant, and 15% cited nonmedical factors. Patients with HF with better LVEF had the highest overall QOL score and less dyspnea burden than those with HF with preserved EF. Independent correlates of HF-dominated diminished QOL were prior cardiac surgery, worse New York Heart Association functional class, renin-angiotensin-aldosterone antagonism, use of diuretic agents, lower body mass index, lower LVEF, and lack of arthritis or history of cancer. CONCLUSIONS: Fewer than one-half of patients with ambulatory HF rated HF as the greatest limitation to their QOL, suggesting that this important outcome will be difficult to affect by HF-targeted therapies alone, particularly in those with higher LVEFs and comorbidities. Patients with HF with better LVEF represent a distinct subtype with better overall QOL. PMID- 26874380 TI - Cost-Effectiveness of Implantable Pulmonary Artery Pressure Monitoring in Chronic Heart Failure. AB - OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the CardioMEMS (CardioMEMS Heart Failure System, St Jude Medical Inc, Atlanta, Georgia) device in patients with chronic heart failure. BACKGROUND: The CardioMEMS device, an implantable pulmonary artery pressure monitor, was shown to reduce hospitalizations for heart failure and improve quality of life in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) trial. METHODS: We developed a Markov model to determine the hospitalization, survival, quality of life, cost, and incremental cost-effectiveness ratio of CardioMEMS implantation compared with usual care among a CHAMPION trial cohort of patients with heart failure. We obtained event rates and utilities from published trial data; we used costs from literature estimates and Medicare reimbursement data. We performed subgroup analyses of preserved and reduced ejection fraction and an exploratory analysis in a lower-risk cohort on the basis of the CHARM (Candesartan in Heart failure: Reduction in Mortality and Morbidity) trials. RESULTS: CardioMEMS reduced lifetime hospitalizations (2.18 vs. 3.12), increased quality-adjusted life-years (QALYs) (2.74 vs. 2.46), and increased costs ($176,648 vs. $156,569), thus yielding a cost of $71,462 per QALY gained and $48,054 per life-year gained. The cost per QALY gained was $82,301 in patients with reduced ejection fraction and $47,768 in those with preserved ejection fraction. In the lower-risk CHARM cohort, the device would need to reduce hospitalizations for heart failure by 41% to cost <$100,000 per QALY gained. The cost-effectiveness was most sensitive to the device's durability. CONCLUSIONS: In populations similar to that of the CHAMPION trial, the CardioMEMS device is cost-effective if the trial effectiveness is sustained over long periods. Post-marketing surveillance data on durability will further clarify its value. PMID- 26874381 TI - Thinking Outside the Box. PMID- 26874382 TI - Bulking Up Skeletal Muscle to Improve Heart Failure Prognosis. PMID- 26874383 TI - Diffusion Capacity and Mortality in Patients With Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction. AB - OBJECTIVES: This study sought to investigate the prognostic importance of a low diffusion capacity of the lung for carbon monoxide (DLCO) in patients with a catheter-based diagnosis of pulmonary hypertension due to heart failure with preserved ejection fraction (PH-HFpEF). BACKGROUND: In patients with pulmonary arterial hypertension, a low DLCO is associated with poor outcome. It is unclear whether the same is true in patients with PH-HFpEF. METHODS: This study retrospectively analyzed clinical characteristics, smoking history, lung function measurements, chest computed tomography, hemodynamics, and survival in 108 patients with PH-HFpEF. The presence of post-capillary PH was determined by right heart catheterization. Patients with moderate or severe lung function abnormalities were excluded. RESULTS: On the basis of previous studies and receiver-operating characteristic curve analysis, the study cohort was divided into patients with a DLCO <45% of the predicted value (DLCO<45%, low DLCO; n = 52) and patients with a DLCO >=45% of the predicted value (DLCO>=45%; n = 56). DLCO<45% was associated with male sex (odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.05 to 6.99; p = 0.039) and smoking history (OR: 5.01; 95% CI: 1.91 to 13.10; p < 0.001). There were no correlations between DLCO and other lung function parameters and hemodynamics. Compared with patients with DLCO>=45%, patients with DLCO<45% had a significantly worse outcome (survival rate at 3 years 36.5% vs. 87.8%, p < 0.001 by log-rank analysis). Cox proportional hazard analysis identified DLCO<45% as an independent predictor of death (hazard ratio: 6.6; 95% CI: 2.6 to 16.9; p < 0.001). CONCLUSIONS: In patients with PH-HFpEF, a low DLCO is strongly associated with mortality. PMID- 26874384 TI - Asymptomatic Left Ventricular Dysfunction: To Screen or Not to Screen? PMID- 26874385 TI - Self-Care and All-Cause Mortality in Patients With Chronic Heart Failure. AB - OBJECTIVES: This study examined the association of self-care with all-cause mortality in a cohort of patients with chronic heart failure (HF). BACKGROUND: Although self-care is crucial to maintain health in patients with chronic HF, studies examining an association with clinical outcomes are scarce. METHODS: Consecutive patients with chronic HF (n = 559, mean age 66.3 +/- 9.5 years, 78% men) completed the 9-item European Heart Failure Self-care Behaviour scale. Our endpoint was all-cause mortality. Associations between self-care and all-cause mortality were assessed with Kaplan-Meier analyses and multivariable Cox regression accounting for standard sociodemographic and clinical covariates, psychological distress, and self-rated health. RESULTS: After a median follow-up of 5.5 +/- 2.4 years (range 16 weeks to 9.9 years), 221 deaths (40%) from any cause were recorded. There was no evidence of a mortality benefit in patients high over those low in global self-care (p = 0.71). In post hoc analyses, low self-reported sodium intake was associated with increased mortality (adjusted hazard ratio: 1.47; 95% confidence interval: 1.10 to 1.96; p = 0.01). Other significant predictors of mortality were: male sex, lack of a partner, New York Heart Association functional class III to IV, and increasing comorbid conditions. CONCLUSIONS: Global self-care was not associated with long-term mortality whereas low self-reported sodium intake independently predicted increased all-cause mortality beyond parameters of disease severity. Replication of findings is needed as well as studies examining the correspondence of subjectively and objectively measured sodium intake and its effects on long-term prognosis in patients with chronic HF. PMID- 26874386 TI - Utility of Patient-Reported Outcome Instruments in Heart Failure. AB - Patient-reported outcomes (PRO) are defined as reports coming directly from patients about how they feel or function in relation to a health condition and its therapy. Although there are numerous compelling reasons why PRO could be an important help in clinical care, they have not evolved into clinical tools integrated into care. The purpose of this review is to assess existing PRO instruments for heart failure with respect to their psychometric properties and potential for use in clinical care. We performed a systematic search of articles published between July 2008 and January 2015 within the MEDLINE, PROMIS, PROQOLID, and Cochrane Library databases. Included instruments had to be developed and tested for heart failure and have had their development processes and psychometric properties described. A total of 31 instruments were identified, 9 of which met all inclusion criteria. After evaluating each remaining instrument in terms of psychometric and clinical criteria and symptom coverage, only 2 instruments-Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaire-met all evaluation criteria. Although clinically useful PRO instruments exist, increasing education to providers on the value and interpretability of PRO instruments, as well as a more streamlined approach to their implementation in the clinical setting is necessary. A clinical trial comparing the routine use of disease-specific PRO with clinical care could further support their incorporation into practice. PMID- 26874387 TI - Chronic Peptide Therapy With B-Type Natriuretic Peptide in Patients With Pre Clinical Diastolic Dysfunction (Stage B Heart Failure). AB - OBJECTIVES: This study determined whether there is development of tachyphylaxis to enhancement of cardiorenal response to acute volume loading (AVL) with B-type natriuretic peptide (BNP) after 12-week, twice-daily subcutaneous BNP administration in patients with preclinical diastolic dysfunction (PDD). BACKGROUND: PDD is characterized by normal systolic function and moderate or severe diastolic dysfunction but no symptoms of heart failure (HF). Impairment in cardiorenal endocrine response to stress by AVL exists in PDD and is corrected by acute administration of subcutaneous BNP. METHODS: A double-blinded, placebo controlled proof-of-concept study was conducted to compare 12 weeks of twice daily subcutaneous BNP, 10 MUg/kg (n = 24), versus placebo (n = 12) in PDD. Subjects underwent 2 study visits, at baseline and after 12 weeks. At each study visit, echocardiography, renal, and neurohumoral assessments were performed before and after intravascular AVL. RESULTS: Among those with PDD, there was a statistically significant improvement in diastolic function after 12 weeks of BNP, as measured by a decrease in the Doppler E/e' ratio (where E is early mitral inflow velocity and e' is mitral annulus early diastolic motion) (p = 0.004) and improvement of diastolic dysfunction grade (p = 0.008). After 12 weeks, there was statistically significantly greater sodium excretion, urine flow, and urinary cyclic guanosine monophosphate excretion to AVL (all p < 0.001), as well as a trend toward greater glomerular filtration rate (p = 0.050) in the BNP group as compared to the placebo group. CONCLUSIONS: In subjects with PDD, chronic BNP administration resulted in sustained improvement in diastolic function without development of tachyphylaxis to the enhancement of cardiorenal response to volume expansion with BNP. (Human Brain Natriuretic Peptide [BNP] [or Nesiritide] to Help Heart, Kidney and Humoral Function; NCT00405548). PMID- 26874388 TI - Interventions Linked to Decreased Heart Failure Hospitalizations During Ambulatory Pulmonary Artery Pressure Monitoring. AB - OBJECTIVES: This study sought to analyze medical therapy data from the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in Class III Heart Failure) trial to determine which interventions were linked to decreases in heart failure (HF) hospitalizations during ambulatory pulmonary artery (PA) pressure-guided management. BACKGROUND: Elevated cardiac filling pressures, which increase the risk of hospitalizations and mortality, can be detected using an ambulatory PA pressure monitoring system before onset of symptomatic congestion allowing earlier intervention to prevent HF hospitalizations. METHODS: The CHAMPION trial was a randomized, controlled, single-blind study of 550 patients with New York Heart Association functional class III HF with a HF hospitalization in the prior year. All patients undergoing implantation of the ambulatory PA pressure monitoring system were randomized to the active monitoring group (PA pressure-guided HF management plus standard of care) or to the blind therapy group (HF management by standard clinical assessment), and followed for a minimum of 6 months. Medical therapy data were compared between groups to understand what interventions produced the significant reduction in HF hospitalizations in the active monitoring group. RESULTS: Both groups had similar baseline medical therapy. After 6 months, the active monitoring group experienced a higher frequency of medications adjustments; significant increases in the doses of diuretics, vasodilators, and neurohormonal antagonists; targeted intensification of diuretics and vasodilators in patients with higher PA pressures; and preservation of renal function despite diuretic intensification. CONCLUSIONS: Incorporation of a PA pressure-guided treatment algorithm to decrease filling pressures led to targeted changes, particularly in diuretics and vasodilators, and was more effective in reducing HF hospitalizations than management of patient clinical signs or symptoms alone. PMID- 26874389 TI - Inflammation in Heart Failure With Preserved Ejection Fraction: Time to Put Out the Fire. PMID- 26874390 TI - One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction. AB - OBJECTIVES: This study sought to determine whether a relatively low single dose or a week-long dosage of dietary inorganic nitrate could improve exercise tolerance in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: Exercise intolerance is the primary manifestation of HFpEF and is largely due to noncardiac factors that reduce oxygen delivery to active skeletal muscles. A recent study showed improved exercise capacity in patients with HFpEF after a single, acute dose of beetroot juice (BRJ) (12.9 mmol inorganic nitrate) while another recent study showed neutral and negative effects of an organic nitrate. METHODS: Twenty HFpEF patients (69 +/- 7 years of age ) were enrolled in an initial cross-over design comparing a single, acute dose of BRJ (6.1 mmol nitrate) to a nitrate-depleted placebo BRJ. A second phase, 1 week of daily doses, used an all-treated design in which patients consumed BRJ for an average of 7 days. The primary outcome of the study was submaximal aerobic endurance, measured as cycling time to exhaustion at 75% of measured maximal power output. RESULTS: No adverse events were associated with the intervention. Submaximal aerobic endurance improved 24% after 1 week of daily BRJ dosing (p = 0.02) but was not affected by the single, acute dose of the BRJ compared to placebo. Consumption of BRJ significantly reduced resting systolic blood pressure and increased plasma nitrate and nitrite in both of the dosing schemes. CONCLUSIONS: One week of daily dosing with BRJ (6.1 mmol inorganic nitrate) significantly improves submaximal aerobic endurance and blood pressure in elderly HFpEF patients. PMID- 26874391 TI - Complementary Role of Arm Circumference to Body Mass Index in Risk Stratification in Heart Failure. AB - OBJECTIVES: This study was performed to investigate the complementary role of arm circumference to body mass index (BMI) in risk stratification of patients with heart failure (HF). BACKGROUND: High BMI is associated with improved survival in patients with HF. However, it does not discriminate between fat and lean muscle as a predominant factor. METHODS: BMI, waist circumference (WC), and mid-upper arm circumference (MUAC) were evaluated in 570 consecutive Japanese patients with HF (mean age 67.4 +/- 14.0 years). Patients were stratified into low and high groups according to BMI, WC, and MUAC and combined into low- or high-BMI and low- or high-WC groups or low- or high-BMI and low- or high-MUAC groups. The endpoint was all-cause mortality. RESULTS: Seventy deaths occurred over a median follow-up period of 1.5 years (interquartile range: 0.7 to 2.8 years). After adjusting for several pre-existing prognostic factors, including Seattle Heart Failure Score and exercise capacity, BMI (hazard ratio [HR]: 0.68; p = 0.016), WC (HR: 0.76; p = 0.044), and MUAC (HR: 0.52; p < 0.001) were all inversely associated with prognosis. Compared with the high-BMI/high-WC group, both the low-BMI/high-WC and low-BMI/low-WC groups showed comparably poorer prognosis. However, the low BMI/low-MUAC group but not the low-BMI/high-MUAC group showed poorer prognosis than the high-BMI/high-MUAC group. Adding MUAC to BMI (0.70 vs. 0.63, p = 0.012) but not WC to BMI (0.64 vs. 0.63, p = 0.763) significantly increased the area under the curve on receiver-operating characteristic curve analysis. CONCLUSIONS: MUAC, but not WC, plays a complementary role to BMI in predicting prognosis in patients with HF. PMID- 26874392 TI - Temporal Trends of Digoxin Use in Patients Hospitalized With Heart Failure: Analysis From the American Heart Association Get With The Guidelines-Heart Failure Registry. AB - OBJECTIVES: The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF). BACKGROUND: Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice in the United States have not been well studied. METHODS: An observational analysis of 255,901 patients hospitalized with HF (117,761 with HFrEF and 138,140 with preserved EF [HFpEF]) from 398 hospitals participating in the Get With The Guidelines-HF registry between January 2005 and June 2014 was conducted to assess the temporal trends and factors associated with digoxin use. RESULTS: Among 117,761 HFrEF patients, only 19.7% received digoxin at discharge. Digoxin prescriptions decreased from 33.1% in 2005 to 10.7% in 2014 (ptrend < 0.0001). Factors associated with digoxin use in HFrEF included atrial fibrillation (AF) (odds ratio [OR]: 2.14; 95% confidence intervals [CI]: 2.02 to 2.28), history of implantable cardioverter defibrillator use (OR: 1.39; 95% CI: 1.32 to 1.46), chronic obstructive pulmonary disease (OR: 1.13, 95% CI: 1.08 to 1.18), diabetes mellitus (OR: 1.10, 95% CI: 1.06 to 1.14), younger age (OR: 0.96, 95% CI: 0.95 to 0.97), lower blood pressure (OR: 0.96, 95% CI: 0.96 to 0.97), and having no history of renal insufficiency (OR: 0.91, 95% CI: 0.85 to 0.97). Use of digoxin in patients with HFpEF (n = 138,140) without AF was 9.8% in 2005, which decreased to 2.2% in 2014 (ptrend < 0.0001). CONCLUSIONS: One in 5 HFrEF patients received digoxin at discharge, with a significant downward temporal trend in use over the study period. Use of digoxin in HFpEF patients without AF was very low and decreased over the study period. PMID- 26874393 TI - Development of a Transplantation Risk Index in Patients With Mechanical Circulatory Support: A Decision Support Tool. AB - OBJECTIVES: The aim of this study was to develop a risk index specific to patients on mechanical circulatory support that accurately predicts 1-year mortality after orthotopic heart transplantation using the United Network for Organ Sharing database. BACKGROUND: Few clinical tools are available to aid in the decision between continuing long-term device support and performing transplantation in patients bridging with mechanical circulatory support. METHODS: Using a prospectively collected, open cohort, 6,036 patients receiving mechanical circulatory support who underwent orthotopic heart transplantation between 2000 and 2013 were evaluated and randomly separated into derivation (80%) and validation (20%) groups. Multivariate logistic regression models were constructed using variables that improved the explanatory power of the model, which was determined using multiple methods. Points for a simple additive risk index were apportioned on the basis of relative effect on odds of 1-year mortality. RESULTS: A 75-point scoring system was created from 9 recipient and 4 donor variables. The average score in the validation cohort was 14.4 +/- 7.7, and scores ranged from 0 to 57; these values were similar to those in the derivation cohort. Each 1-point increase predicted an 8.3% increase in the odds of 1-year mortality (odds ratio: 1.08; 95% confidence interval: 1.06 to 1.11). Low (0 to 10), intermediate (11 to 20), and high (>20) risk score cohorts were created, with predicted average 1-year mortalities of 8.6%, 12.8%, and 31%, respectively, in the validation cohort. CONCLUSIONS: The investigators present a novel, internally cross-validated risk index that accurately predicts mortality in bridge-to-transplantation patients. PMID- 26874394 TI - We Are Not Alone: Understanding the Contributions of Intestinal Microbial Communities and the Congested Gut in Heart Failure. PMID- 26874395 TI - Effect of predischarge blood pressure on follow-up outcomes in patients with severe hypertension in the ED. AB - BACKGROUND: Although emergency department (ED) patients with asymptomatic severe hypertension (ASH) generally have no serious short-term hypertension-related adverse events, it is unclear whether persistently high discharge blood pressure (BP) affects the outcome due to the dynamic nature of BP. OBJECTIVES: This study aims to investigate the effect of predischarge BP on short-term follow-up results for ED patients with ASH. METHODS: The prospective observational study was performed in the ED of a tertiary care hospital during a 3-month period. Adult patients who had systolic BP >=180 mm Hg and diastolic BP >=100 mm Hg without acute end-organ damage were enrolled and treated at the emergency physicians' discretion. Discharge BP was precategorized into severely high and moderately high groups. We compared the groups using direct telephone contact and medical record reviews of follow-up BP within 1 week and identified their related adverse events. RESULTS: One hundred and forty-six eligible cases were identified in this study; 1 patient (0.7%) had a serious hypertension-related adverse event. One hundred and thirteen patients had follow-up BP information available. There was no difference in mean systolic BP and diastolic BP at follow-up between patients who were discharged from the ED with severely high vs moderately high BP. CONCLUSION: Predischarge BP value is not associated with immediate serious adverse events and does not affect short-term BP control in ED patients with ASH. Further study on the need to lower BP during the ED stay and on antihypertensive prescriptions for these patients is required. PMID- 26874396 TI - Morphine in the setting of acute myocardial infarction: pros and cons. PMID- 26874397 TI - The molecular structure of thio-ether fatty acids influences PPAR-dependent regulation of lipid metabolism. AB - Thio-ether fatty acids (THEFAs), including the parent 2-(tetradecylthio)acetic acid (TTA), are modified fatty acids (FAs) that have profound effects on lipid metabolism given that they are blocked for beta-oxidation, and able to act as peroxisome proliferator-activated receptor (PPAR) agonists. Therefore, TTA in particular has been tested clinically for its therapeutic potential against metabolic syndrome related disorders. Here, we describe the preparation of THEFAs based on the TTA scaffold with either a double or a triple bond. These are tested in cultured human skeletal muscle cells (myotubes), either as free acid or following esterification as phospholipids, lysophospholipids or monoacylglycerols. Metabolic effects are assessed in terms of cellular bioavailabilities in myotubes, by FA substrate uptake and oxidation studies, and gene regulation studies with selected PPAR-regulated genes. We note that the inclusion of a triple bond promotes THEFA-mediated FA oxidation. Furthermore, esterification of THEFAs as lysophospholipids also promotes FA oxidation effects. Given that the apparent clinical benefits of TTA administration were offset by dose limitation and poor bioavailability, we discuss the possibility that a selection of our latest THEFAs and THEFA-containing lipids might be able to fulfill the therapeutic potential of the parent TTA while minimizing required doses for efficacy, side-effects and adverse reactions. PMID- 26874398 TI - Giant retroperitoneal liposarcoma: The silent tumour. PMID- 26874399 TI - [How can we decrease mortality due to anastomotic fistula in colorectal surgery?]. PMID- 26874400 TI - [Management of postpartum ovarian vein thrombosis. The experience of Amiens university hospital]. AB - OBJECTIVES: Postpartum ovarian vein thrombophlebitis is an uncommon complication that may threaten mothers' lives. The extension of thrombosis in the inferior vena cava causes a pulmonary embolisme risk and requires urgent care. The main objective of this study was, from a series of patients, to determine the clinical and paraclincal signs to suggest the diagnosis of postpartum ovarian vein thrombosis. Secondary objectives were to assess the location and extent of thrombosis and the therapeutic management of this disease at the University Hospital of Amiens. METHODS: A retrospective study was performed in the Obstetrics and Gynecology department of Amiens University Hospital between January 2011 and May 2015. Were included in this study all patients for whom the diagnosis of postpartum ovarian thrombophlebitis was confirmed by computed tomography. RESULTS: Thirteen patients had postpartum thrombosis of the ovarian vein. The incidence of this disease in our series was 0.13%. The average age of patients was 30 years. The median onset of symptoms was located on the 4th day; in 92% of cases, they appeared within 10 days after delivery. The clinical picture was not specific and the main symptoms were fever (46.1%) and abdominal pain (53.8%). Biologically inflammatory syndrome was commonly found with elevated leukocytes and CRP. Bacteriological samples were in most cases negative. Sixty nine percent of lesions concerned the right ovarian vein; 23% had renal extension, 53.8% had inferior vena cava extension and 23% got complicated with pulmonary embolism. No maternal deaths were reported. One hundred percent of patients received anticoagulation at curative dose, the mean duration of which was 6 months. In all, 84.6% of patients received in combination antibiotic therapy with oral and parenteral initially broad spectrum. CONCLUSION: Ovarian postpartum thrombosis is a rare complication that must be evoked and sought, especially in front of a non-septic febrile abdominal pain syndrome in postpartum. PMID- 26874402 TI - Simple N(epsilon)-thioacetyl-lysine-containing cyclic peptides exhibiting highly potent sirtuin inhibition. AB - Transforming a linear pentapeptidic pan-SIRT1/2/3 inhibitor harboring the catalytic mechanism-based sirtuin inhibitory warhead N(epsilon)-thioacetyl-lysine into its side chain-to-side chain cyclized derivatives was able to furnish highly potent SIRT1/2/3 inhibition (low nM). This finding attests to the feasibility of developing structurally simple yet highly potent catalytic mechanism-based cyclic peptidic sirtuin inhibitors. PMID- 26874401 TI - Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes. AB - Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles. PMID- 26874403 TI - Synthesis and anticancer evaluation of spermatinamine analogues. AB - Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 MUM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. PMID- 26874404 TI - A unique macrolactam derivative via a [4+6]-cycloaddition from Streptomyces niveus. AB - One new macrolactam derivative, nivelactam (1) and one new polyenoic acid derivative, niveamide (2), along with two other known 20-atom macrolactams (3 and 4) were isolated from the fermentation broth of Streptomyces niveus, which obtained from the forest soil in northeastern China. The structures of 1 and 2 were elucidated on the basis of HRESIMS, IR, and NMR spectroscopic data analyses. Compound 1 was proposed as an intramolecular [4+6]-cycloaddition product of 3 by S. niveus, and displayed moderate cytotoxic activity against a panel of human tumor cell lines in vitro, with IC50 values ranging from 3.76 +/- 0.58 to 15.02 +/- 2.81 MUM. PMID- 26874405 TI - Occupational exposure to infection risk and use of personal protective equipment by emergency medical personnel in the Republic of Korea. AB - BACKGROUND: Few studies of occupational exposure (OE) to infectious risk among emergency medical personnel (EMP) or their use of personal protective equipment (PPE) have been conducted in the Republic of Korea. OBJECTIVE: To determine the status of OE to infectious risks and use of PPE. METHODS: A convenience sample of 907 questionnaires (response rate, 88.5%) was collected from September 1, 2014, to January 31, 2015, in 5 metropolitan Korean cities. RESULTS: Respiratory diseases were significantly prevalent (44.5%) and influenza (29.5%) was the most frequently reported illness. An exposure report was only made in 19.5% of cases. The primary reason for OE report noncompletion was the complexity of the reporting process (23.9%). A total of 365 participants reported OE to body fluids and blood (40.2%) with needlestick injury being the most frequent OE type (17.6%). More than 5 years of job experience (47.8%) (P < .001) and region (city) (P = .003) significantly increased OE to body fluids and blood. Puncture resistant containers (71.9%) and disposable gloves (68.9%) were used. Job training and education on infection risks and use of PPE were not uniformly conducted (77.5%). Anxiety about OE to risk of infection from patients was common among EMP (63.2%). CONCLUSIONS: EMP experienced significant OE to infectious risk and use PPE inadequately. Surveillance and education programs regarding OE should be developed. PMID- 26874406 TI - The influence of intensive care unit-acquired central line-associated bloodstream infection on in-hospital mortality: A single-center risk-adjusted analysis. AB - OBJECTIVE: To explore the risk-adjusted association between intensive care unit (ICU)-acquired central line-associated bloodstream infection (CLABSI) and in hospital mortality. DESIGN: Retrospective observational study. SETTING: Forty five-bed adult ICU. PATIENTS: All non-extracorporeal membrane oxygenation ICU admissions between July 1, 2008, and April 30, 2014, requiring a central venous catheter (CVC), with a length of stay > 48 hours, were included. METHODS: Data were extracted from our infection prevention and ICU databases. A multivariable logistic regression model was constructed to identify independent risk factors for ICU-acquired CLABSI. The propensity toward developing CLABSI was then included in a logistic regression of in-hospital mortality. RESULTS: Six thousand three hundred fifty-three admissions were included. Forty-six cases of ICU acquired CLABSI were identified. The overall CLABSI rate was 1.12 per 1,000 ICU CVC-days. Significant independent risk factors for ICU-acquired CLABSI included: double lumen catheter insertion (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.16-5.77), CVC exposure > 7 days (OR, 2.07; 95% CI, 1.06-4.04), and CVC insertion before 2011 (OR, 2.20; 95% CI, 1.22-3.97). ICU-acquired CLABSI was crudely associated with greater in-hospital mortality, although this was attenuated once the propensity to develop CLABSI was adjusted for (OR, 1.20; 95% CI, 0.54-2.68). CONCLUSIONS: A greater propensity toward ICU-acquired CLABSI was independently associated with higher in-hospital mortality, although line infection itself was not. The requirement for prolonged specialized central venous access appears to be a key risk factor for ICU-acquired CLABSI, and likely informs mortality as a marker of persistent organ dysfunction. PMID- 26874407 TI - A systematic approach for developing a ventilator-associated pneumonia prevention bundle. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) is among the most common type of health care-associated infection in the intensive care unit and is associated with significant morbidity and mortality. Existing VAP prevention intervention bundles vary widely on the interventions included and in the approaches used to develop these bundles. The objective of this study was to develop a new VAP prevention bundle using a systematic approach that elicits clinician perceptions on which interventions are most important and feasible to implement. METHODS: We identified potential interventions to include through a review of current guidelines and literature. We implemented a 2-step modified Delphi method to gain consensus on the final list of interventions. An interdisciplinary group of clinical experts participated in the Delphi process, which was guided by a technical expert panel. RESULTS: We identified 65 possible interventions. Through the Delphi method, we narrowed that list to 19 interventions that included 5 process and 14 structural measures. CONCLUSIONS: We described a structured approach for developing a new VAP prevention bundle. Obtaining clinician input on what interventions to include increases the likelihood that providers will adhere to the bundle. PMID- 26874408 TI - Utility of a single nasal polymerase chain reaction assay in predicting absence of skin and environmental contamination in hospitalized patients with past methicillin-resistant Staphylococcus aureus. AB - We evaluated hospitalized patients with a history of methicillin-resistant Staphylococcus aureus (MRSA) for persistent colonization and need for contact precautions. Up to 3 daily cultures of nares, skin, and any present wounds were compared with a single nasal polymerase chain reaction (PCR) assay. Most patients (76.2%) were no longer colonized with MRSA. A single PCR assay was sufficient to exclude persistent colonization and environmental contamination and remove the contact precautions. PMID- 26874409 TI - Successful development of a direct observation program to measure health care worker hand hygiene using multiple trained volunteers. AB - BACKGROUND: Direct observation of health care worker (HCW) hand hygiene (HH) remains the gold standard, but implementation is challenging. Our objective was to develop an accurate HH observation program using multiple HCW volunteers. METHODS: HH compliance was defined as correct HH performed before and after contact with a patient or a patient's environment. HCW volunteers from each unit at our children's hospital were trained by infection preventionists to covertly collect HH observations during routine care using an electronic tool. Questionnaires sent to observers in February and December 2014 recorded demographic characteristics, observation time, and scenarios assessing accuracy. HCWs were surveyed regarding their awareness that their HH behavior was being recorded. RESULTS: There were 146 HH observers. The majority of observers reported making 1-2 observations per shift (65%) and taking <=10 minutes recording an observation (85%). Between January 2012 and December 2014 there were 22,484 HH observations (average, 622 per month), including nurses (46%), physicians (21%), and other HCWs (33%). Observers correctly recorded HH behavior more than 90% of the time in 5 of the 6 scenarios. Most HCWs (86%) were unaware they were being observed. CONCLUSION: A direct observation program staffed by multiple HCW volunteers can inexpensively and accurately collect HCW HH data. PMID- 26874410 TI - Australian milk fat--Seasonal and regional variation of melting properties. AB - The solid fat content and dropping point of milk fat obtained over 2 yr and from 19 bulk milk production sites across Australia were characterized. Solid fat content at 5 degrees C and 20 degrees C, respectively, ranged between 49.9 and 66.1% and between 14.6 and 29.6% across all sites. Dropping point ranged between 30.5 and 35.4 degrees C. The dropping point did not correlate with solid fat content at lower temperatures across several sites, indicating that it is not an accurate or useful measure of functionality at temperatures of 15 degrees C or below. Although at times, considerable variation was observed in milk fat melting properties between sites located in similar geographic regions, statistical analysis by means of boxplots and multidimensional scaling revealed broad similarities within regions over the 24 mo. Multidimensional scaling also revealed similarities between some quite distant and diverse regions (e.g., Queensland and South Australia with constant and seasonal production, respectively). These analyses were used to make 5 groups from the 19 sites to describe seasonal melting properties. The groups with sites in west Victoria, southeast Victoria, and Tasmania showed the largest seasonal variation and range of values, with peaks and lows in southeast Victoria and Tasmania occurring up to 3 mo later than in west Victoria. The group with sites in New South Wales, Queensland, and South Australia had the least variation and range of values, which were relatively high throughout. The group with Western Australian sites showed medium levels of variation but distinct seasonal patterns, with solids fats typically below and dropping points higher than the national average. The Victorian group's lows in dropping point occurred about 2 mo later than did the low values of solid fat content. No single factor stood out as determining the variation in melting properties. PMID- 26874411 TI - Effect of salt stress on morphology and membrane composition of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum, and their adhesion to human intestinal epithelial-like Caco-2 cells. AB - The effects of NaCl reduction (10.0, 7.5, 5.0, 2.5, and 0% NaCl) and its substitution with KCl (50% substitution at each given concentration) on morphology of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium longum was investigated using transmission electron microscopy. Changes in membrane composition, including fatty acids and phospholipids, were investigated using gas chromatography and thin layer chromatography. Adhesion ability of these bacteria to human intestinal epithelial-like Caco-2 cells, as affected by NaCl and its substitution with KCl, was also evaluated. Bacteria appeared elongated and the intracellular content appeared contracted when subjected to salt stress, as observed by transmission electron microscopy. Fatty acid content was altered with an increase in the ratio of unsaturated to saturated fatty acid content on increasing the NaCl-induced stress. Among the phospholipids, phosphatidylglycerol was reduced, whereas phosphatidylinositol and cardioplipin were increased when the bacteria were subjected to salt stress. There was a significant reduction in adhesion ability of the bacteria to Caco-2 cells when cultured in media supplemented with NaCl; however, the adhesion ability was improved on substitution with KCl at a given total salt concentration. The findings provide insights into bacterial membrane damage caused by NaCl. PMID- 26874412 TI - Effects of reducing dietary starch content by replacing barley grain with wheat dried distillers grains plus solubles in dairy cow rations on ovarian function. AB - Our objective was to evaluate the effects of dietary starch content, altered by partial substitution of dietary grain with wheat dried distillers grain with solubles (DDGS), on the interval from calving to first ovulation, concentrations of hormones and metabolites in plasma and follicular fluid, and granulosa cell gene expression in preovulatory follicles. Sixty lactating dairy cows were assigned to 1 of 2 diets from calving until 84d postpartum. Diets were formulated to contain either 17.3% rolled barley grain (29.2% starch) or 17.2% wheat DDGS (19.1% starch), with 43.0% barley silage and 21.6% rolled corn grain as the other major ingredients (dry matter basis). Transrectal ultrasonography was performed twice weekly to monitor ovarian dynamics from 7 +/- 2d postpartum until ovulation or until 56d in milk, whichever occurred earlier. Plasma concentrations of insulin and insulin-like growth factor-1 (IGF-1) were determined in all 60 cows, and that of glucose, fatty acids, and urea in a subset of 24 cows, representing those in which the first ovulation occurred spontaneously within 5 wk postpartum. Estradiol (proestrus) and progesterone (12d postovulation) in plasma were also measured. Concentrations of insulin, IGF-1, glucose, fatty acids, and urea were determined in follicular fluid (wk 9), and the expression of LH receptor, estrogen receptor beta, cytochrome P450 aromatase, and plasma type glutathione peroxidase genes measured in granulosa cells obtained from the preovulatory follicles at wk 9 postpartum in the subset of 24 cows. Diets did not alter the interval from calving to first ovulation (32.3 +/- 2.5d), but a significantly lower proportion of cows on the DDGS diet (20%) ovulated multiple (>= 2) follicles at the first ovulation than those on the barley grain diet (40%). The incidence of multiple ovulations tended to be lower at first insemination (10 vs. 21% for cows fed DDGS and barley grain diets, respectively). Mean plasma concentration of insulin was higher in cows fed the barley grain diet (2.5 vs 1.6 IU/mL), and a diet by time interaction was noted, with cows on the barley grain ration having higher insulin from wk 6 to 12 postpartum; however, mean plasma IGF 1 concentration did not differ between dietary groups. In the subsets, mean plasma concentrations of metabolites or estradiol and progesterone were not affected by diet, parity, or diet by parity interactions. Cows on the DDGS diet had lower concentrations of IGF-I (69 vs. 108 ng/mL) and higher fatty acids (222 vs. 149 mEq/L) in the follicular fluid obtained from preovulatory follicles. Diet, parity, and diet by parity interactions did not affect the concentrations of insulin, glucose, urea, estradiol, and progesterone in follicular fluid. Diets did not alter the expression profiles of LHr, estrogen receptor beta, CYP19, and GPx3 genes in granulosa cells. In summary, diets did not affect the interval from calving to first ovulation or granulosa cell gene expression. However, reducing dietary starch content by a partial replacement of dietary grain with wheat DDGS increased fatty acids in follicular fluid and reduced the concentrations of insulin in plasma, IGF-1 in follicular fluid, and the incidence of multiple ovulations. PMID- 26874413 TI - Evaluation of udder health parameters and risk factors for clinical mastitis in Dutch dairy herds in the context of a restricted antimicrobial usage policy. AB - Recently, many changes have been implemented in Dutch dairy herds. Herd sizes have increased and antimicrobial use has been reduced. Certain types of antimicrobials can only be used in specific circumstances, and the preventive use of antimicrobials in dry cows is prohibited. The aim of this study was to quantify clinical mastitis (CM), subclinical mastitis (SCM), and risk factors associated with CM in Dutch dairy herds in 2013, in the context of these changes. For this study, 240 dairy herds were randomly selected from farms that participated in test-day milk recording, used a conventional milking system, and agreed to participate in the study. Eventually, 233 Dutch dairy farmers had complete records of CM in their herds in 2013 and 224 of these farmers completed a questionnaire on management factors potentially associated with CM. All participating farmers gave consent to use their routinely collected herd data such as test-day records and cow identification and registration data. Clinical and subclinical mastitis incidence rate (CMI and SCMI, respectively) per 100 cows per year, subclinical mastitis prevalence, and average bulk tank milk somatic cell count were obtained for 2013. The risk factor analysis was conducted using a generalized linear model with a log link function and a negative binomial distribution on herd level in Stata 13.1. A median CMI of 28.6 per 100 cows at risk per year, SCMI of 70.1 per 100 cows at risk per year, SCM prevalence of 15.8%, and bulk tank milk somatic cell count of 171 * 10(3) cells/mL were observed in 2013. Factors that were significantly associated with a higher CMI were cleaning slatted floors only once per day compared with more than 4 times a day (i.e., mechanical), a higher percentage of Holstein Friesian cows present in the herd, treating less than 50% of the cows with CM with antimicrobials, postmilking teat disinfection, and treatment of cows with elevated somatic cell count with antimicrobials. The results of this study indicated that udder health had not deteriorated compared with udder health in previous Dutch studies where herd sizes were somewhat smaller and before the restrictions in antimicrobial use. Several of the risk factors that were found can be influenced by the farmer and can prevent the occurrence of CMI. Still, when cases of CM occur, treatment with antimicrobials might be necessary to cure the CM case and is beneficial for the overall udder health in the herd. PMID- 26874414 TI - Invited review: Growth-promoting effects of colostrum in calves based on interaction with intestinal cell surface receptors and receptor-like transporters. AB - The postnatal development and maturation of the gastrointestinal (GI) tract of neonatal calves is crucial for their survival. Major morphological and functional changes in the calf's GI tract initiated by colostrum bioactive substances promote the establishment of intestinal digestion and absorption of food. It is generally accepted that colostrum intake provokes the maturation of organs and systems in young calves, illustrating the significance of the cow-to-calf connection at birth. These postnatal adaptive changes of the GI tissues in neonatal calves are especially induced by the action of bioactive substances such as insulin-like growth factors, hormones, or cholesterol carriers abundantly present in colostrum. These substances interact with specific cell-surface receptors or receptor-like transporters expressed in the GI wall of neonatal calves to elicit their biological effects. Therefore, the abundance and activity of cell surface receptors and receptor-like transporters binding colostral bioactive substances are a key aspect determining the effects of the cow-to-calf connection at birth. The present review compiles the information describing the effects of colostrum feeding on selected serum metabolic and endocrine traits in neonatal calves. In this context, the current paper discusses specifically the consequences of colostrum feeding on the GI expression and activity of cell receptors and receptor-like transporters binding growth hormone, insulin-like growth factors, insulin, or cholesterol acceptors in neonatal calves. PMID- 26874415 TI - The influence of casein haplotype on morphometric characteristics of fat globules and fatty acid composition of milk in Italian Holstein cows. AB - The aim of this work was to investigate the effect of casein haplotypes (alphaS1 , beta-, and kappa-caseins) on morphometric characteristics of fat globules and fatty acid composition of Italian Holstein milk. Casein haplotypes were determined by isoelectric focusing; milk fat globule size was measured by using a fluorescence microscope; and fatty acid profile was determined by gas chromatography. Casein haplotype significantly affected the fat globule size, the percentage incidence of each globule size class on total measured milk fat globules, and fatty acid composition. A higher incidence of smaller milk fat globules was associated with the BB-A(2)A(2)-BB genotype (alphaS1-, beta-, and kappa-casein haplotypes, respectively), whereas small globules were not detected in BB-A(2)A(1)-AA milk, but that milk had the highest percentage of large globules. A higher content of monounsaturated fatty acids was associated with the BB-A(2)A(2)-AB genotype, whereas higher contents of conjugated linoleic acid and docosahexaenoic acid were detected in BB-A(1)A(1)-AA milk. Our results indicate that casein haplotype could affect fat characteristics and, therefore, the nutritional and technological quality of milk. PMID- 26874416 TI - Invited review: Influence of climatic conditions on the development, performance, and health of calves. AB - The objective of this review is to provide the reader with an overview of thermoregulatory mechanisms and the influence of climatic conditions in different housing systems on the development, performance, and health of calves. Thermic stress is observed in association with extreme temperatures and large temperature variations, but other variables such as relative humidity and wind speed can also contribute to thermic stress. Thermoregulation in calves is similar to that in adult cattle, but especially dystocial calves are more prone to heat loss. Heat or cold stress results in direct economic losses because of increased calf mortality and morbidity, as well as indirect costs caused by reduced weight gain, performance, and long-term survival. The climatic conditions in a variety of housing systems, associated health problems, and strategies to mitigate thermic stress are discussed in this review. The goal of housing is to alleviate the effect of climate on calves and provide a microclimate. Adequate ventilation with fresh air is essential to reduce respiratory disease. Common practices such as raising calves in individual outdoor enclosures have been challenged lately. Recent research seeks to evaluate the suitability of group housing under practical, economic, and animal welfare considerations. Limited results for reducing thermic stress can be achieved by simple measures such as shades or shelter, but additional heat or cold stress relieving strategies can be required depending on the housing system. PMID- 26874417 TI - Role of milk protein-based products in some quality attributes of goat milk yogurt. AB - Goat milk yogurts were manufactured with the fortification of 2% (wt/vol) skim goat milk powder (SGMP), sodium caseinate (NaCn), whey protein concentrate (WPC), whey protein isolate (WPI), or yogurt texture improver (YTI). Yogurts were characterized based on compositional, microbiological, and textural properties; volatile flavor components (with gas chromatography); and sensory analyses during storage (21d at 5 degrees C). Compared with goat milk yogurt made by using SGMP, the other goat milk yogurt variants had higher protein content and lower acidity values. Goat milk yogurts with NaCn and WPC, in particular, had better physical characteristics. Using WPI caused the hardest structure in yogurt, leading to higher syneresis values. Acetaldehyde and ethanol formation increased with the incorporation of WPI, WPC, or YTI to yogurt milk. The tyrosine value especially was higher in the samples with NaCn and YTI than in the samples with WPC and WPI. Counts of Streptococcus thermophilus were higher than the counts of Lactobacillus delbrueckii ssp. bulgaricus, possibly due to a stimulatory effect of milk protein based ingredients other than SGMP on the growth of S. thermophilus. Yogurt with NaCn was the best accepted among the yogurts. For the parameters used, milk protein-based products such as NaCn or WPC have promising features as suitable ingredients for goat milk yogurt manufacture. PMID- 26874418 TI - Comparison of milk oxidation by exposure to LED and fluorescent light. AB - Light-induced oxidation of milk has been well studied. Exposure of milk to UV light facilitates the oxidation of fats to aldehydes, and the degradation of sulfur-containing amino acids, both of which contribute to off-flavors. In addition, vitamin A and riboflavin are easily degraded by UV light. These reactions occur rapidly and are exacerbated by bright fluorescent lights in retail dairy cases. The invention of white light-emitting diodes (LED) may provide a solution to this oxidation problem. In this study, fresh milk containing 1% fat and fortified with vitamin A and riboflavin was exposed to LED at 4,000 lx, or fluorescent light at 2,200 lx for 24 h. Milk samples exposed to LED or fluorescent light, as well as milk protected from light, were analyzed by a consumer acceptance panel, and a trained flavor panel. In addition, vitamin A, riboflavin, and the production of volatile compounds were quantified. Exposure to light resulted in a reduction of cooked/sweet, milkfat, and sweet flavors and increased the intensity of butterscotch, cardboard, and astringency. In general, exposure to fluorescent light resulted in greater changes in the milk than exposure to LED even though the LED was at higher intensity. Consumers were able detect off-flavors in milk exposed to fluorescent light after 12 h and LED after 24 h of exposure. The riboflavin and vitamin A content was reduced by exposure to fluorescent light, whereas there was no significant reduction caused by LED compared with the non-light-exposed control. Production of hexanal, heptanal, 2 heptanal, octanal, 2-octanal nonanal, dimethyl sulfide, and caproic acid vinyl ester from the light-induced degradation of fats was significantly higher with fluorescent than LED. Production of these compounds was significantly higher with both light treatments than in the control milk. This study indicates that LED is less destructive to milk than fluorescent light. PMID- 26874419 TI - Short communication: Prevalence, antimicrobial resistance, and resistant traits of coagulase-negative staphylococci isolated from cheese samples in Turkey. AB - A total of 17 coagulase-negative staphylococci (CNS) isolates obtained from 72 cheese samples were included in this study. Coagulase-negative staphylococci isolates obtained in this study comprised 6 (35.3%) Staphylococcus saprophyticus, 3 (17.6%) Staphylococcus epidermidis, 2 (11.8%) Staphylococcus hominis, 2 (11.8%) Staphylococcus haemolyticus, 1 (5.9%) Staphylococcus xylosus, 1 (5.9%) Staphylococcus vitulinus, 1 (5.9%) Staphylococcus lentus, and 1 (5.9%) Staphylococcus warneri. The disc diffusion assay revealed that the highest occurrence of resistance was found for penicillin (76.5%), erythromycin (35.3%), tetracycline (29.4%), and trimethoprim-sulfamethoxazole (17.6%) among CNS isolates. However, all CNS isolates were found to be susceptible to vancomycin, streptomycin, linezolid, and gentamycin. Of the isolates, 64.7% carried at least one of the following antimicrobial resistance genes: mecA, tet(M), erm(B), blaZ, ant(4')-la, aph(3')-IIIa, and lnu(A). The results suggest that improved hygienic conditions, such as safer handling of raw milk, proper cleaning, and sanitation during the manufacturing in the dairies, are urgently needed in Turkey. PMID- 26874420 TI - The effect of bovine somatotropin on the cost of producing milk: Estimates using propensity scores. AB - Annual farm-level data from New York dairy farms from the years 1994 through 2013 were used to estimate the cost effect from bovine somatotropin (bST) using propensity score matching. Cost of production was computed using the whole-farm method, which subtracts sales of crops and animals from total costs under the assumption that the cost of producing those products is equal to their sales values. For a farm to be included in this data set, milk receipts on that farm must have comprised 85% or more of total receipts, indicating that these farms are primarily milk producers. Farm use of bST, where 25% or more of the herd was treated, ranged annually from 25 to 47% of the farms. The average cost effect from the use of bST was estimated to be a reduction of $2.67 per 100 kg of milk produced in 2013 dollars, although annual cost reduction estimates ranged from statistical zero to $3.42 in nominal dollars. Nearest neighbor matching techniques generated a similar estimate of $2.78 in 2013 dollars. These cost reductions estimated from the use of bST represented a cost savings of 5.5% per kilogram of milk produced. Herd-level production increase per cow from the use of bST over 20 yr averaged 1,160 kg. PMID- 26874421 TI - Mastitis prevention and control practices and mastitis treatment strategies associated with the consumption of (critically important) antimicrobials on dairy herds in Flanders, Belgium. AB - The main objectives of this study were to evaluate to what extent variations in herd-level antimicrobial consumption (AMC) can be explained by differences in management practices that are consistently effective in the prevention of (sub)clinical mastitis, on the one hand, and by differences in mastitis treatment strategies, on the other hand. Antimicrobial consumption data were obtained during 2012 and 2013 by "garbage can audits" and expressed as antimicrobial treatment incidences (ATI) for all compounds combined (total ATI) and for the critically important antimicrobials for human health separately. Data on mastitis prevention and control practices were obtained via face-to-face interviews performed during herd visits in March 2013. Some management practices and treatment strategies related to udder health were associated with the total AMC. However, the results demonstrated that implementing effective udder health management practices does not necessarily imply a low AMC and vice versa. Herds participating in a veterinary herd health management program and herds selectively drying off cows used fewer antimicrobials compared with herds not participating in such a program or applying blanket dry-cow therapy. Moreover, herds treating (some) (sub)clinical mastitis cases with intramammary homeopathic substances consumed fewer antimicrobials than herds not applying such homeopathic treatments. Besides these factors, no other direct association was found between effective udder health management practices on the one hand and AMC on the other hand. Also, the use of critically important antimicrobials was only associated with the way in which subclinical mastitis cases were treated. The latter indicates that the AMC of critically important antimicrobials is potentially driven by factors other than those included in this study such as those related to the "mindset" of the veterinarians and their farmers. Future research should therefore aim to unravel the reasoning of vets and their farmers behind the use of those critically important antimicrobials for the treatment of mastitis and other diseases. PMID- 26874422 TI - Analysis of behavioral changes in dairy cows associated with claw horn lesions. AB - Detecting lame cows is important in improving animal welfare. Automated tools are potentially useful to enable identification and monitoring of lame cows. The goals of this study were to evaluate the suitability of various physiological and behavioral parameters to automatically detect lameness in dairy cows housed in a cubicle barn. Lame cows suffering from a claw horn lesion (sole ulcer or white line disease) of one claw of the same hind limb (n=32; group L) and 10 nonlame healthy cows (group C) were included in this study. Lying and standing behavior at night by tridimensional accelerometers, weight distribution between hind limbs by the 4-scale weighing platform, feeding behavior at night by the nose band sensor, and heart activity by the Polar device (Polar Electro Oy, Kempele, Finland) were assessed. Either the entire data set or parts of the data collected over a 48-h period were used for statistical analysis, depending upon the parameter in question. The standing time at night over 12 h and the limb weight ratio (LWR) were significantly higher in group C as compared with group L, whereas the lying time at night over 12 h, the mean limb difference (?weight), and the standard deviation (SD) of the weight applied on the limb taking less weight were significantly lower in group C as compared with group L. No significant difference was noted between the groups for the parameters of heart activity and feeding behavior at night. The locomotion score of cows in group L was positively correlated with the lying time and ?weight, whereas it was negatively correlated with LWR and SD. The highest sensitivity (0.97) for lameness detection was found for the parameter SD [specificity of 0.80 and an area under the curve (AUC) of 0.84]. The highest specificity (0.90) for lameness detection was present for Deltaweight (sensitivity=0.78; AUC=0.88) and LWR (sensitivity=0.81; AUC=0.87). The model considering the data of SD together with lying time at night was the best predictor of cows being lame, accounting for 40% of the variation in the likelihood of a cow being lame (sensitivity=0.94; specificity=0.80; AUC=0.86). In conclusion, the data derived from the 4-scale weighing platform, either alone or combined with the lying time at night over 12 h, represent the most valuable parameters for automated identification of lame cows suffering from a claw horn lesion of one individual hind limb. PMID- 26874423 TI - Invited review: Effects of group housing of dairy calves on behavior, cognition, performance, and health. AB - Standard practice in the dairy industry is to separate the calf and dam immediately after birth and raise calves in individual pens during the milk feeding period. In nature and in extensive beef systems, the young calf lives in a complex social environment. Social isolation during infancy has been associated with negative effects, including abnormal behavior and developmental problems, in a range of species. Here, we review empirical work on the social development of calves and the effects of social isolation in calves and other species; this evidence indicates that calves reared in isolation have deficient social skills, difficulties in coping with novel situations, as well as specific cognitive deficits. We also review the practices associated with group housing of dairy calves, and discuss problems and suggested solutions, especially related to cross sucking, competition, aggression, and disease. The studies reviewed indicate that social housing improves solid feed intakes and calf weight gains before and after calves are weaned from milk to solid feed. Evidence regarding the effects of social housing on calf health is mixed, with some studies showing increased risk of disease and other studies showing no difference or even improved health outcomes for grouped calves. We conclude that there is strong and consistent evidence of behavioral and developmental harm associated with individual housing in dairy calves, that social housing improves intakes and weight gains, and that health risks associated with grouping can be mitigated with appropriate management. PMID- 26874424 TI - Advances in production and simplified methods for recovery and quantification of exopolysaccharides for applications in food and health. AB - The capacity of strains to produce exopolysaccharides (EPS) is widespread among species of lactic acid bacteria and bifidobacteria, although the physiological role of these molecules is not yet clearly understood. When EPS are produced during food fermentation, they confer technological benefits on the fermented end products, such as improved texture and stability. In addition, some of these EPS may have beneficial effects on consumer health. These uses of EPS necessitate optimal and sufficient production of these molecules, both in situ and ex situ, not only to improve their yields but also to obtain a particular functionality. The present study reviews the commonly used methods of production, isolation, and quantification that have been used in recent studies dealing with EPS-producing lactic acid bacteria and bifidobacteria. PMID- 26874425 TI - Consumers' attitudes about milk quality and fertilization methods in dairy cows in Germany. AB - Major advances in assisted reproductive technologies have improved reproductive efficiency in dairy cattle. However, these developments occurred regardless of the perception of consumers, who often distrust biotechnology in food production. Therefore, the objective of this study was to investigate consumers' attitudes toward reproductive management practices in dairy cattle. In November 2012, 1,646 participants were interviewed by a commercial market research institute. Participants were selected from all regions and demographic categories to represent the general public in Germany. Seven questions regarding milk-drinking preferences and reproductive technologies were asked in face-to-face interviews. Descriptive statistics and multivariable logistic regression models were used. The majority of people drank milk at least weekly (63%) and found the taste of milk important (60%). Most people perceived advanced reproductive technologies negatively [e.g., the use of sexed semen (53%), embryo transfer (58%), cloning (81%), and hormone treatments to increase fertility (65%)]. Many people lacked basic knowledge about milk production (22% did not know that cows only give milk after calving; 51% did not know that milk naturally contains hormones); however, participants with a high school education, older participants, and those who had concerned themselves with dairy farming were more knowledgeable. Education and providing information might help to inform the public about reproductive management practices in dairy cows. PMID- 26874426 TI - Effect of maternal nutrition and days of gestation on pituitary gland and gonadal gene expression in cattle. AB - This study investigated effects of maternal overnutrition on gonadal development and pituitary-gonadal gene expression in cattle fetuses at mid- and late gestation. Twenty-seven multiparous dry cows were fed either high (ad libitum, H) or moderate (M) intake of the same diet. Twelve cows from H (n=6) and M (n=6) intake carrying females fetuses were euthanized at 199 and 268d of gestation (DG; n=3 for H or M on each DG). Fifteen cows from H (n=6) and M intake (n=9) carrying male fetuses were euthanized at 139, 199, and 241 DG (n=2 for H and n=3 for M on each DG). Fetal gonads and pituitary gland were sampled for gene expression and histological analyses. Sex-specific responses to maternal intake were observed. Primordial and total follicle numbers were lower in fetal ovaries from H than in M intake cows. These results were the reverse for preantral and antral follicles. Volumetric proportion and diameter of seminiferous cord were lower in fetal testis of H than M intake cows. The expression level of FSHB was greater in pituitary gland of the female fetus from H compared with M intake cows, irrespective of DG, whereas LHB gene expression did not differ. In males, FSHB and LHB gene expression levels were similar between maternal intake groups. Fetal ovarian expression of P450 aromatase, StAR, BMPR2, TGFBR1, GDF9, FSHR, Bax, and CASP3 genes were higher in H than in M intake cows, irrespective of DG. Fetal testicular expression of StAR, HSD17B3, IGF1, IGF2, and IGF1R genes was higher in M than in H intake cows. The differences in gene expression for steroidogenesis, folliculogenesis, and apoptosis may explain the distinct pattern of follicular growth between offspring of M and H intake cows. By contrast, the lower volumetric proportion, diameter, and length of seminiferous cord may relate to decreased gene expression in fetal testis from H intake cows. In conclusion, maternal H intake seems to affect fetal ovarian follicular growth and number of follicles, which may affect the size of ovarian reserve in their offspring. In male fetus, maternal H intake seems to disturb testicular development and may have implications on sperm production. The underlying mechanism of differential gene expression and the effect on offspring reproductive potential should be the focus of further research, especially considering larger sample size, reducing the chance for type I errors. PMID- 26874427 TI - Raman spectroscopy as an effective screening method for detecting adulteration of milk with small nitrogen-rich molecules and sucrose. AB - Adulteration of milk for commercial gain is acknowledged as a serious issue facing the dairy industry. Several analytical techniques can be used to detect adulteration but they often require time-consuming sample preparation, expensive laboratory equipment, and highly skilled personnel. Here we show that Raman spectroscopy provides a simple, selective, and sensitive method for screening milk, specifically for small nitrogen-rich compounds, such as melamine, urea, ammonium sulfate, dicyandiamide, and for sucrose. Univariate and multivariate statistical methods were used to determine limits of detection and quantification from Raman spectra of milk spiked with 50 to 1,000 mg/L of the N-rich compounds and 0.25 to 4% sucrose. Partial least squares (PLS) calibration provided limit of detection minimum thresholds <200mg/L (0.02%) for the 4 N-rich compounds and <0.8% for sucrose, without the need for surface-enhanced Raman spectroscopy. The results show high reproducibility (7% residual standard deviation) and 100% efficiency for screening of milk for these adulterants. PMID- 26874428 TI - Orthodontic treatment mediates dental pulp microenvironment via IL17A. AB - OBJECTIVE: Orthodontic treatment induces dental tissue remodeling; however, dental pulp stem cell (DPSC)-mediated pulp micro-environmental alteration is still largely uncharacterized. In the present study, we identified elevated interleukin-17A (IL17A) in the dental pulp, which induced the osteogenesis of DPSCs after orthodontic force loading. DESIGN: Tooth movement animal models were established in Sprague-Dawley rats, and samples were harvested at 1, 4, 7, 14, and 21 days after orthodontic treatment loading. DPSC self-renewal and differentiation at different time points were examined, as well as the alteration of the microenvironment of dental pulp tissue by histological analysis and the systemic serum IL17A expression level by an ELISA assay. In vitro recombinant IL17A treatment was used to confirm the effect of IL17A on the enhancement of DPSC self-renewal and differentiation. RESULTS: Orthodontic treatment altered the dental pulp microenvironment by activation of the pro-inflammatory cytokine IL17A in vivo. Orthodontic loading significantly promoted the self-renewal and differentiation of DPSCs. Inflammation and elevated IL17A secretion occurred in the dental pulp during orthodontic tooth movement. Moreover, in vitro recombinant IL17A treatment mimicked the enhancement of the self-renewal and differentiation of DPSCs. CONCLUSIONS: Orthodontic treatment enhanced the differentiation and self-renewal of DPSCs, mediated by orthodontic-induced inflammation and subsequent elevation of IL17A level in the dental pulp microenvironment. PMID- 26874429 TI - MicroRNA-144 is unlikely to play a role in bronchiolitis obliterans syndrome. PMID- 26874430 TI - Intracellular lipid dysregulation interferes with leukocyte function in the ovaries of meat-type hens under unrestricted feed intake. AB - Meat-type Red-feather country hens fed ad libitum (AD-hens) exhibit obesity associated morbidities and a number of ovarian irregularities. Leukocyte participations in ovarian activities are unstudied in AD-hens. In contrast to feed-restricted hens (R-hens), ovulatory process of the F1 follicle appeared delayed in AD-hens in association with reduced F1 follicle progesterone content, gelatinase A (MMP-2) and collagenase-3 (MMP-13) activities coincident with elevated IL-1beta and no production (P<0.05), and increased leukocyte infiltration of inflamed necrotic follicle walls. Extracts of AD-hen F1 follicle walls induced greater leukocyte migration than extracts from F1 follicle wall extracts of R-hens (P<0.05). Co-cultures of granulosa cells with increasing numbers of leukocytes from either AD-hens or R-hens exhibited dose dependent reductions in progesterone production and increases in cell death. AD-hen leukocytes were less proapoptotic than their R counterparts (P<0.05). Granulosa MMP-13 and MMP-2 activities were also suppressed in the co-cultures with heterophils or monocytes in a dose-dependent manner (P<0.05). AD heterophils and R monocytes had a greater inhibitory effect on MMP activities in the co-cultures than their respective counterparts (P<0.05). Both basal and LPS-induced IL-1beta secretion and MMP-22 or MMP-2 activities in freshly isolated AD-hen leukocytes were reduced (P<0.05). Exposure of AD or R leukocytes to 0.5mM palmitate impaired IL-1beta secretion and MMP-22 or MMP-2 activity. Inhibition of ceramide synthesis with FB1 and ROS production with n-MPG scavenging rescued MMP activity and IL 1beta production in palmitate treated heterophils, but exacerbated monocyte suppression. These latter findings suggest that intracellular lipid dysregulation in leukocytes contributes to ovarian dysfunction in AD-hens. PMID- 26874431 TI - Letter to the Editor on "Preoperative Mapping in Unicompartmental Knee Arthroplasty Using Computed Tomography Scans Is Associated With Radiation Exposure and Carries High Cost". PMID- 26874432 TI - Characterization of dissolved organic matter for prediction of trihalomethane formation potential in surface and sub-surface waters. AB - Dissolved organic matter (DOM) in surface waters used for drinking purposes can vary markedly in character dependent on their sources within catchments. The character of DOM further influences the formation of disinfection by products when precursor DOM present in drinking water reacts with chlorine during disinfection. Here we report the development of models that describe the formation potential of trihalomethanes (THMFP) dependent on the character of DOM in waters from discrete catchments with specific land-use and soil textures. DOM was characterized based on UV absorbance at 254 nm, apparent molecular weight and relative abundances of protein-like and humic-like compounds. DOM character and Br concentration (up to 0.5 mg/L) were used as variables in models (R(2)>0.93) of THMFP, which ranged from 19 to 649 MUg/L. Chloroform concentration (12-594 MUg/L) and relative abundance (27-99%) were first modeled (R(2)>0.85) and from these, the abundances of bromodichloromethane and chlorodibromomethane estimated using power and exponential functions, respectively (R(2)>0.98). From these, the abundance of bromoform is calculated. The proposed model may be used in risk assessment of catchment factors on formation of trihalomethanes in drinking water, in context of treatment efficiency for removal of organic matter. PMID- 26874433 TI - The use of pilocarpine eye drops for estimating the time since death. AB - OBJECTIVE: The objective of this study was to estimate the time since death using pilocarpine eye drops. METHODS: In this study, 100 postmortem cases with known time of death were included. In each case, the left pupil was measured in millimeter units using a vernier caliper, and pilocarpine eye drops were applied. The pupil was measured again 10 min later, and statistical analysis was used to analyze the correlation between the time since death and the change in the pupil. RESULTS: The longest duration since death that the pupils showed reaction to pilocarpine was 15 h. The correlation between the change in the pupil and the postmortem interval was found (Spearman's rho, r = -0.304, p = 0.002), and the change in the pupil may be used to predict the postmortem interval by the following regression equation: postmortem interval (PMI) = 8.310-3.702 (Diff) +/- 0.735 (PMI was postmortem interval in hours and Diff was the difference in the size of the pupil after administering pilocarpine in millimeter units). CONCLUSION: The present study showed that pilocarpine eye drops can be used to estimate the time since death. PMID- 26874434 TI - Evaluating the temporal trend of completed suicides referred to the Iranian Forensic Medicine Organization during 2006-2010. AB - OBJECTIVE: The objective of the present study was to determine the temporal trend of the rate of completed suicides in Iran during 2006-2010. MATERIAL AND METHODS: Data on completed suicides were collected from the national suicide registry of the Iranian Forensic Medicine Organization. The rates were calculated for males and females for each year of the study period, from which the temporal trends were determined. Statistical analyses were conducted using SPSS software, using chi-squared and analysis of variance (ANOVA) tests. RESULTS: The overall rate of suicide was 4.7/100,000, with a male/female ratio of 2.4. The mean age of suicide was 31.9 years, which was significantly higher in males. Hanging was the most common method, followed by poisoning and self-immolation. During the study period, the rate of drug poisoning almost doubled, while that of firearms halved. The rates of hanging and self-immolation also increased in the last years of the study period. CONCLUSION: According to the results of this study, it can be concluded that Iran has had a constant rate of completed suicides over the past decade. Our study also indicated the need for future nationwide studies on the risk factors of suicidal behavior and on different suicide methods in the entire Iranian population. PMID- 26874435 TI - A new formula for assessing skeletal age in growing infants and children by measuring carpals and epiphyses of radio and ulna. AB - The aim of this study is to develop a specific formula for the purpose of assessing skeletal age in a sample of Italian growing infants and children by measuring carpals and epiphyses of radio and ulna. A sample of 332 X-rays of left hand-wrist bones (130 boys and 202 girls), aged between 1 and 16 years, was analyzed retrospectively. Analysis of covariance (ANCOVA) was applied to study how sex affects the growth of the ratio Bo/Ca in the boys and girls groups. The regression model, describing age as a linear function of sex and the Bo/Ca ratio for the new Italian sample, yielded the following formula: Age = -1.7702 + 1.0088 g + 14.8166 (Bo/Ca). This model explained 83.5% of total variance (R(2) = 0.835). The median of the absolute values of residuals (observed age minus predicted age) was -0.38, with a quartile deviation of 2.01 and a standard error of estimate of 1.54. A second sample test of 204 Italian children (108 girls and 96 boys), aged between 1 and 16 years, was used to evaluate the accuracy of the specific regression model. A sample paired t-test was used to analyze the mean differences between the skeletal and chronological age. The mean error for girls is 0.00 and the estimated age is slightly underestimated in boys with a mean error of -0.30 years. The standard deviations are 0.70 years for girls and 0.78 years for boys. The obtained results indicate that there is a high relationship between estimated and chronological ages. PMID- 26874436 TI - Major mental disorders, gender, and criminological circumstances of homicide. AB - OBJECTIVE: To examine the criminological circumstances of homicide in a group of French murderers with and without major mental disorders (MMD) stratified by the perpetrator's gender. METHODS: Sociodemographic, clinical, and criminological variables were collected from the psychiatric expert reports of 210 cases of homicide heard at the High Court of Angers, France. Murderers were categorized according to MMD diagnosis and gender. RESULTS: Among 210 murderers, 17.6% (n = 37) had a MMD (20% of the female perpetrators). Logistic regression models showed that being a murderer with a MMD was associated with younger age (adjusted Odds Ratio OR = 1.03, P = 0.034), high school education (OR = 2.48, P = 0.036), previous use of psychiatric services (OR = 4.75, P = 0.003), alcohol intoxication (OR = 2.71, P = 0.027), and delusional state (OR = 3.96, P = 0.002) at the time of the homicide. Multiple correspondence analyses showed that female murderers with a MMD were more prone to have depression and to use drowning as a method than those without a MMD, and that male murderers with a MMD more often had a high school education and delusional beliefs at the time of the homicide than those without a MMD. CONCLUSION: Specific profiles of criminological circumstances of homicide could help to explore the risk of homicide in female and male patients with a MMD. PMID- 26874437 TI - Performance of primary repair on colon injuries sustained from low-versus high energy projectiles. AB - Among various reasons, colon injuries may be caused by low- or high-energy firearm bullets, with the latter producing a temporary cavitation phenomenon. The available treatment options include primary repair and two-stage management, but recent studies have shown that primary repair can be widely used with a high success rate. This paper investigates the differences in performance of primary repair on these two types of colon injuries. Two groups of patients who sustained colon injuries due to single gunshot wounds, were retrospectively categorized based on the type of bullet. Primary colon repair was performed in all patients selected based on the inclusion and exclusion criteria (Stone and Fabian's criteria). An almost absolute homogeneity was attained among the groups in terms of age, latent time before surgery, and four trauma indexes. Only one patient from the low-energy firearm projectile group (4%) developed a postsurgical complication versus nine patients (25.8%) from the high-energy group, showing statistically significant difference (p = 0.03). These nine patients experienced the following postsurgical complications: pneumonia, abscess, fistula, suture leakage, and one multiorgan failure with sepsis. Previous studies concluded that one-stage primary repair is the best treatment option for colon injuries. However, terminal ballistics testing determined the projectile's path through the body and revealed that low-energy projectiles caused considerably lesser damage than their high-energy counterparts. Primary colon repair must be performed definitely for low-energy short firearm injuries but very carefully for high energy injuries. Given these findings, we suggest that the treatment option should be determined based not only on the bullet type alone but also on other clinical findings. PMID- 26874438 TI - Co-fermentation of acetate and sugars facilitating microbial lipid production on acetate-rich biomass hydrolysates. AB - The process of lignocellulosic biomass routinely produces a stream that contains sugars plus various amounts of acetic acid. As acetate is known to inhibit the culture of microorganisms including oleaginous yeasts, little attention has been paid to explore lipid production on mixtures of acetate and sugars. Here we demonstrated that the yeast Cryptococcus curvatus can effectively co-ferment acetate and sugars for lipid production. When mixtures of acetate and glucose were applied, C. curvatus consumed both substrates simultaneously. Similar phenomena were also observed for acetate and xylose mixtures, as well as acetate rich corn stover hydrolysates. More interestingly, the replacement of sugar with equal amount of acetate as carbon source afforded higher lipid titre and lipid content. The lipid products had fatty acid compositional profiles similar to those of cocoa butter, suggesting their potential for high value-added fats and biodiesel production. This co-fermentation strategy should facilitate lipid production technology from lignocelluloses. PMID- 26874439 TI - Microbiological mechanism of the improved nitrogen and phosphorus removal by embedding microbial fuel cell in Anaerobic-Anoxic-Oxic wastewater treatment process. AB - Anaerobic-Anoxic-Oxic (AA/O) wastewater treatment process is a widely used wastewater treatment process for simultaneous nitrogen and phosphorus removal. Microbial fuel cell (MFC) can generate electricity and treat the organic wastewater simultaneously. Our previous research showed that embedding MFC in AA/O wastewater treatment process could enhance the pollutants removal efficiency. However, the mechanism was not clear. In this study, a lab-scale corridor-style AA/O reactor with MFC embedded was operated and both the total nitrogen and total phosphorus removal efficiencies were enhanced. DGGE and Illumina Miseq results demonstrated that both the microbial community structures on the surface of the cathode and in the suspensions of cathode chamber have been changed. The percentage of Thauera and Emticicia, identified as denitrifying bacteria, increased significantly in the suspension liquid when the MFC was embedded in the AA/O reactor. Moreover, the genus Rheinheimera were significantly enriched on the cathode surface, which might contribute to both the nitrogen removal enhancement and electricity generation. PMID- 26874440 TI - Illumina MiSeq sequencing reveals the key microorganisms involved in partial nitritation followed by simultaneous sludge fermentation, denitrification and anammox process. AB - A combined process including a partial nitritation SBR (PN-SBR) followed by a simultaneous sludge fermentation, denitrification and anammox reactor (SFDA) was established to treat low C/N domestic wastewater in this study. An average nitrite accumulation rate of 97.8% and total nitrogen of 9.4mg/L in the effluent was achieved during 140days' operation. The underlying mechanisms were investigated by using Illumina MiSeq sequencing to analyze the microbial community structures in the PN-SBR and SFDA. Results showed that the predominant bacterial phylum was Proteobacteria in the external waste activated sludge (WAS, added to the SFDA) and SFDA while Bacteroidetes in the PN-SBR. Further study indicated that in the PN-SBR, the dominant nitrobacteria, Nitrosomonas genus, facilitated nitritation and little nitrate was generated in the PN-SBR effluent. In the SFDA, the co-existence of functional microorganisms Thauera, Candidatus Anammoximicrobium and Pseudomonas were found to contribute to simultaneous sludge fermentation, denitrification and anammox. PMID- 26874441 TI - Catalytic pyrolysis of wheat bran for hydrocarbons production in the presence of zeolites and noble-metals by using TGA-FTIR method. AB - Pyrolysis of wheat bran with or without catalysts was investigated using TGA-FTIR method in order to determine the influence of zeolite and noble metal catalysts on the evolution profile and relative yield of the volatile compounds. The addition of all catalysts decreased the volatile matter of wheat bran from 76.3% to 75.9%, 73.9%, 73.5%, 69.7% and increased the solid residue from 18.0% to 18.4%, 20.4%, 20.8%, 24.6% under the catalyst of ZSM-5, 5% Pd/C, MCM-41, and 5% Pt/C. Noble-metal catalysts had higher activity for deoxygenation of compounds containing carbonyl, carboxyl, and hydroxyl groups than zeolites. Degradation of nitrogen containing compounds atom proceeded better in presence of zeolites. Noble-metal catalysts promoted formation of aromatics and changed the profiles of evolved compounds whereas zeolites advanced formation of aliphatics and olefins. PMID- 26874442 TI - Effects of interspecific competition on the growth of macrophytes and nutrient removal in constructed wetlands: A comparative assessment of free water surface and horizontal subsurface flow systems. AB - The outcome of competition between adjoining interspecific colonies of Phragmites and Typha in two large field pilot-scale free water surface (FWS) and subsurface flow (SSF) CWs is evaluated. According to findings, the effect of interspecific competition was notable for Phragmites australis, whereby it showed the highest growth performance in both FWS and SSF wetland. In a mixed-culture, P. australis demonstrates superiority in terms of competitive interactions for space between plants. Furthermore, the interspecific competition among planted species seemed to cause different ecological responses of plant species in the two CWs. For example, while relatively high density and shoot height determined the high aboveground dry weight of P. australis in the FWS wetland, this association was not evident in the SSF. Additionally, while plants nutrients uptake accounts for a higher proportion of the nitrogen removal in FWS, that in the SSF accounts for a higher proportion of the phosphorous removal. PMID- 26874443 TI - Does inter-tibiofibular graft still have a role in the treatment of lower-limb non-union? AB - INTRODUCTION: Tibial non-union is a complication that poses a real challenge for surgeons. Several forms of treatment, depending on the type of non-union, have been described. The present study sought to assess results for treatment of tibial non-union by inter-tibiofibular graft (ITFG). MATERIAL AND METHOD: An exhaustive cohort study was performed on the files of 33 patients: 25 male, 8 female; mean age, 44years. Twenty cases involved high-energy trauma. Twenty-four were open fractures. Twenty-two concerned diaphyseal fracture, 10 of which were complex segmental. Eleven concerned distal fracture, including 4 complete articular fractures. There were 17 cases of septic non-union. There were no cases of severe bone defect. ITFG was performed at a mean 8.7 months post-trauma, as first-line treatment in 30 cases and in second line in 3. RESULTS: Thirty-one patients showed bone consolidation, at a mean 7.2 months. The 2 failures resulted from technical error. Trauma kinetics emerged as a risk factor for failure. DISCUSSION: ITFG remains a useful treatment option in tibial non-union, whether infected or not. The present results are comparable with those of the literature. Although the present series comprised only tight non-union, a study of the literature showed that ITFG can treat bone defects up to 4 or 5cm. Functional results showed tibiotalar joint stiffening, due more to immobilization and non weight-bearing than to syndesmosis. ITFG thus remains relevant to the treatment of tibial non-union. LEVEL OF EVIDENCE: IV, retrospective study. PMID- 26874444 TI - Intercondylar notch dysplasia in open-physis anterior cruciate ligament injuries: A case-control study. AB - BACKGROUND: The incidence of anterior cruciate ligament (ACL) tears in children is rising steadily due to a variety of factors including growing participation in sports. A narrow intercondylar notch is an intrinsic risk factor that is well documented in adults but rarely investigated in children. The objective of this study was to evaluate the potential association between a narrow intercondylar notch and ACL tears in children. HYPOTHESIS: A narrow intercondylar notch is associated with ACL tears. MATERIAL AND METHODS: In a paediatric case-control study, we compared intercondylar notch morphology as assessed by magnetic resonance imaging (MRI) in 49 patients with ACL tears (33 males and 16 females with a mean age of 13.6 years) and 50 controls with normal knees (18 boys and 32 girls with a mean age of 13.8 years). In each participant, posterior tibial slope was measured, as well as the notch width index (NWI) (width of the intercondylar notch over bicondylar width at the same level). In addition, to evaluate anterior impingement, the angle formed by Blumensaat's line and the axis of the tibia (alpha angle) was measured with the knee extended. RESULTS: The NWI was significantly lower in the cases than in the controls (0.244+/-0.02 and 0.263+/ 0.02, respectively; P<0.05). The alpha angle was also significantly smaller in the cases (138.74 degrees +/-4.6 degrees vs. 141.30 degrees +/-7.9 degrees in the controls; P<0.05). DISCUSSION: ACL tears are associated with a small NWI in children. A narrow intercondylar notch is an established risk factor for ACL tears and should be sought routinely to determine whether notch-plasty should be performed during the ACL reconstruction procedure in order to decrease the risk of recurrent ACL tears. LEVEL OF EVIDENCE: III, case-control study. PMID- 26874445 TI - Bone lengthening using the Fitbone((r)) motorized intramedullary nail: The first experience in France. AB - INTRODUCTION: Intramedullary limb lengthening systems include mechanical systems (the Albizzia nail and the ISKD nail) as well as motorized systems with the Fitbone((r)) (Wittenstein, Igersheim, Germany) and the Precice((r)) (Ellipse Technologies, Irvine, CA, USA) nails. We hypothesized that limb lengthening using the Fitbone((r)) nail was reliable, reproducible, and comfortable for the patient. PATIENTS AND METHODS: Between 2010 and 2013, a prospective single center, single-operator (FA) study was conducted on patients who had undergone limb lengthening using the Fitbone((r)) nail. The inclusion criteria were length discrepancy of the limbs equal to or greater than 25 mm or a short stature. The exclusion criteria were indications for cosmetic reasons and/or growth plates that were still open. The lengthening parameters were assessed postoperatively and at the last follow-up. Lengthening was considered achieved when the lengthening objective did not differ by more than 5 mm. All complications were noted. A statistical analysis was performed. RESULTS: Twenty-six Fitbone((r)) nails were implanted in 23 patients, in the femur in 15 cases and the tibia in 11 cases. The patients' mean age was 22.5 years (range: 15-53 years) and the mean follow-up was 3.4 years (range: 2-5.3 years). The limb lengthening targeted was obtained in 23 cases (88%) and the mean lengthening was 45.3+/-18 mm (range: 20 80 mm). The mean time to healing was 277+/-167 days (range: 86-638 days). The mean healing index was 73+/-57 days/cm for the femurs and 83.5+/-65 days/cm for the tibias. The mean complication rate was 15.4%. DISCUSSION: This study emphasizes the good short-term results of this motorized intramedullary lengthening system. An evaluation over the longer term and with a higher number of patients remains necessary. LEVEL OF EVIDENCE: IV: uncontrolled, prospective, continuous study. PMID- 26874446 TI - Aneurysmal bone cyst: A 19-case series managed by percutaneous sclerotherapy. AB - INTRODUCTION: Sclerotherapy offers an alternative to surgery for the treatment of aneurysmal bone cyst (ABC). The main objective of the present study was to assess the radiological efficacy of sclerotherapy in terms of ossification on MRI. Secondary objectives were to assess clinical efficacy on pain evaluation and to analyze recurrence and complications according to type of sclerosing agent and intraoperative imaging technique. MATERIALS AND METHODS: Between 2006 and 2014, 19 patients (7 females, 12 males, aged 3 to 17 years) with ABC treated by sclerotherapy were included. Six received Ethibloc((r)), 9 Aetoxisclerol((r)), 2 liquid absolute alcohol, and 2 absolute alcohol gel. Assessment used fluoroscopy in 17 cases and CT in 2. Ossification was assessed on MRI and pain on a visual analog scale and HEDEN score. RESULTS: Ossification was complete in 11 cases (84.6%) and partial in 2 (15.4%). Eighteen patients (94.7%) were pain-free at 3 months. There was no recurrence, at a minimum 2 years' follow-up. One case of skin necrosis was observed, associated with use of liquid absolute alcohol; there was 1 case of arterial reflux of Ethibloc((r)) under CT control. DISCUSSION: Sclerotherapy enables minimally invasive treatment of lesions that are deep, difficult of access to surgery and potentially damaging. Use of absolute alcohol gel and fluoroscopic control seems to improve the risk/benefit ratio, limiting complications by vascular extravasation of the sclerosing agent, thanks to real time visualization of diffusion. Its clinical and radiological efficacy makes sclerotherapy and alternative primary treatment choice in ABC. LEVEL OF EVIDENCE: IV, retrospective study. PMID- 26874447 TI - Can the presence of an infection be predicted before a revision total hip arthroplasty? Preliminary study to establish an infection score. AB - INTRODUCTION: The diagnosis of periprosthetic joint infection can be challenging, in part because there is no universal diagnostic test. Current recommendations include several diagnostic criteria, and are mainly based on the results of deep microbiological samples; however, these only provide a diagnosis after surgery. A predictive infection score would improve the management of revision arthroplasty cases. The purpose of this study was to define a composite infection score using standard clinical, radiological and laboratory data that can be used to predict whether an infection is present before a total hip arthroplasty (THA) revision procedure. HYPOTHESIS: The infection score will make it possible to differentiate correctly between infected and non-infected patients in 75% of cases. MATERIAL AND METHODS: One hundred and four records from patients who underwent THA revision for any reason were analysed retrospectively: 43 with infection and 61 without infection. There were 54 men and 50 women with an average age of 70+/-12 years (range 30-90). A univariate analysis was performed to look for individual discriminating factors between the data in the medical records of infected and non-infected patients. A multivariate analysis subsequently integrated these factors together. A composite score was defined and its diagnostic effectiveness was evaluated as the percentage of correctly classified records, along with its sensitivity and specificity. RESULTS: The score consisted of the following individually weighed factors: body mass index, presence of diabetes, mechanical complication, wound healing disturbance and fever. This composite infection score was able to distinguish correctly between the infected patients (positive score) and non-infected patients (negative score) in 78% of cases; the sensitivity was 57% and the specificity 93%. DISCUSSION: Once this score is evaluated prospectively, it could be an important tool for defining the medical - surgical strategy during THA revision, no matter the reason for revision. LEVEL OF EVIDENCE: Level IV - retrospective study. PMID- 26874448 TI - Repeated metal ion measurement in patients with bilateral metal on metal (ASRTM) hip replacements. AB - BACKGROUND: Blood metal ion measurements have become a cornerstone in the surveillance of metal-on-metal (MoM) hip replacements. Interpretation of these levels in patients with bilateral MoM hip replacements, however, is challenging. We therefore asked (1) if there is a clinically significant change in whole blood (WB) Co or Cr levels in repeated WB assessment in patients operated on with bilateral ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) (Co<5.0MUg/L, Cr<7.4MUg/L) in the repeated WB metal ion assessment. HYPOTHESIS: We hypothesized that there is a significant difference between repeated Co and Cr level measurement performed within one year+/-4 months interval in patients with bilateral ASR hip replacements. MATERIALS AND METHODS: We identified all patients (n=139) who had received bilateral ASR hip replacements (278 hips). Patients (n=76, 152 hips) who had undergone two blood metal ion measurements within eight to sixteen months' time interval were included in the study analysis. Study cohort included 38 patients with bilateral ASR hip resurfacings (mean age 53 years, median follow-up 4.6 years, median femoral diameter 51mm) and 38 patients with bilateral ASR XL total hip replacements (mean age 60 years, median follow-up 3.6 years, median femoral diameter 49mm). RESULTS: There was no significant change in Co and Cr levels between the repeated measurements in the HR cohort. Both Co and Cr were significantly higher in the THR cohort in the repeated measurement (Co: 8.3MUg/L vs. 12.6MUg/L, Cr: 3.15MUg/L vs. 3.4MUg/L, both P<0.001). WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with bilateral high risk HR device. In contrast to this, 21.1% of patients with THRs had WB Co ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group. DISCUSSION: Annual blood metal ion measurement is not useful in patients with bilateral hip resurfacings who have undergone at least one preliminary screening including both metal ion measurement and cross-sectional imaging. It seems, however, to be beneficial in patients with bilateral high risk MoM THR. LEVEL OF EVIDENCE: Level III (retrospective comparative study). PMID- 26874449 TI - Femoral revision with a primary cementless stem. AB - INTRODUCTION: The use of a primary cementless component is a tempting option for revision total hip arthrosplasty (reTHA), however, the results of this type of revision have not been clearly determined. The goal of this retrospective study was to determine: if revision with a primary anatomical cementless femoral stem gives adequate bone fixation; the rate of secondary subsidence or recurrent loosening; the survival rate with this device. HYPOTHESIS: Revision with a primary anatomical cementless femoral stem results in a low rate of subsidence and recurrent loosening. MATERIALS AND METHODS: This retrospective series of 43 reTHA performed between 1994 and 2012 included 43 patients, mean age 66 years old (37-90) with a minimum follow-up of 24months. There were grade 1 (n=24) or 2A (n=19) bone defects according to the Paprosky classification. The causes of revision were: aseptic loosening in 27, septic loosening in 6, malposition of the implant in 7 and periprosthetic fractures in 3. Clinical (Postel Merle d'Aubigne [PMA] and Harris scores), and radiological (subsidence) assessment was performed, as well as survival analysis (with a 95% confidence interval). RESULTS: All components were changed through posterolateral approach without femorotomy. In four cases de-escalation (use of a primary component for secondary revision of a prior revision component) was performed. There were no perioperative fractures or perforations. After a mean 47months (24-134), the mean PMA score increased from 10 (5-15) to 16 (11-18), and the Harris score from 58 (20-80) to 85 (66-96). Radiological assessment did not show any extensive radiolucencies or secondary subsidence. Only 3 components were placed in a varus position, with no clinical consequences. One patient had subsequent revision for recurrent dislocations. Estimated survival at 80months by Kaplan-Meier analysis was 85% (CI 95%: 64 100%). DISCUSSION: There are very few studies in the literature (7 series) on this topic, which shows the reluctance of surgeons to use this technique. Placement of a primary femoral stem requires good metaphyseal bone quality for primary stability. Thus, the indication is limited to Paprosky 1 and 2A stages. Revision surgery must be performed by endofemoral approach requiring good preoperative planning, as well as knowledge of the explanted component and a revision component must be available, if necessary, in the operating room. LEVEL OF EVIDENCE: Retrospective study, level 4. PMID- 26874450 TI - Diabetes mellitus and risk of ischemic stroke in patients with heart failure and no atrial fibrillation. AB - OBJECTIVE: The risk of ischemic stroke, systemic thromboembolism, and all-cause death among heart failure patients previously diagnosed with diabetes mellitus is poorly described. We evaluated the risk of these endpoints among heart failure patients without diagnosed atrial fibrillation according to the presence of diabetes mellitus. METHODS: Population-based nationwide cohort study of non anticoagulated patients diagnosed with incident heart failure during 2000-2012, identified by record linkage between nationwide registries in Denmark. We calculated relative risks after 1year to evaluate the association between diabetes and risk of events in 39,357 heart failure patients, among whom 18.1% had diabetes. Analysis took into account competing risks of death. RESULTS: Absolute risks of all endpoints were higher in patients with diabetes compared to patients without diabetes after 1-year follow-up (ischemic stroke: 4.1% vs. 2.8%; systemic thromboembolism: 11.9% vs. 8.6%; all-cause death: 22.1% vs. 21.4%). Diabetes was significantly associated with an increased risk of ischemic stroke (adjusted relative risk [RR]: 1.27, 95% confidence interval [CI]: 1.07-1.51); systemic thromboembolism (RR: 1.20, 95% CI: 1.11-1.30); and all-cause death (RR: 1.17, 95% CI: 1.11-1.23). Additionally, time since diabetes diagnosis was associated with higher adjusted cumulative incidences of ischemic stroke, systemic thromboembolism, and all-cause death (p for trend, p<0.001). CONCLUSIONS: Among heart failure patients without atrial fibrillation, diabetes was associated with a significantly increased risk of ischemic stroke, systemic thromboembolism, and all-cause death compared to those without diabetes, even after adjustment for concomitant cardiovascular risk factors. Increased focus on secondary prevention in heart failure patients with diabetes may be warranted. PMID- 26874451 TI - Percutaneous closure of three atrial septal defects with three interleaved atrial septal occluders in an adult patient. PMID- 26874452 TI - Predictive value of the SYNTAX score for short-term cognitive outcomes after off pump coronary artery bypass surgery. PMID- 26874453 TI - Increased creatine kinase with statin treatment may identify statin-associated muscle symptoms. PMID- 26874454 TI - Sudden death: A growing threat to doctors in China. PMID- 26874455 TI - Pathogen-driven treatment strategy in new onset dilated cardiomyopathy. Impact on ventricular function and clinical outcome. PMID- 26874456 TI - Factors Influencing Female Caregivers' Appraisals of Their Preschoolers' Behaviors. AB - INTRODUCTION: This study used the Resiliency Model of Family Stress, Adjustment, and Adaptation to explore family factors associated with primary female caregivers' appraisals of children's behaviors, distortion of their appraisals, and children's risk of having behavioral problems. METHOD: A cross-sectional, correlational design was used. Data were collected from female caregivers of preschoolers. Instruments measured demographic characteristics, comfort in parenting, appraisal of behaviors, daily and parenting stress, depressive symptoms, social support, ratings of children's behaviors, and distortion in ratings. Analyses included chi2 and simultaneous linear regression. RESULTS: Greater parenting discomfort and daily stress were associated with lower appraisals of children's behaviors. Caucasian race and higher distortion in behavioral ratings were associated with higher risk of behavioral problems. Caregiver's appraisal was associated with daily stress level and parenting comfort. DISCUSSION: Additional research is needed regarding how these factors affect children's behavior and causes of distorted parental views of children's behaviors. PMID- 26874457 TI - Quality of Life and Health Outcomes in Overweight and Non-Overweight Children With Asthma. AB - BACKGROUND: During the past two decades, the number of children and adolescents who are obese has more than doubled. Following this trend in childhood obesity, there has been an alarming increase in the number of children with asthma who are overweight. OBJECTIVE: The aim of this study was to examine the differences in quality of life (QOL) and health outcomes of obese and overweight children with asthma compared with normal-weight children with asthma using a descriptive comparative survey design. METHODS: This comparative study consisted of 90 overweight and normal-weight 9- to 14-year-olds with asthma. Health outcomes examined included asthma-related missed number of school days, emergency department (ED) visits, hospitalizations, number of days wheezing, and number of night awakenings. QOL was measured using the Pediatric Asthma Quality of Life Questionnaire. RESULTS: The obese group reported the highest percentage of ED visits, hospitalizations, and number of days wheezing compared with the normal weight group. A risk ratio analysis showed that the obese group had an overall 2.73 (95% confidence interval [CI] 2.15, 3.63) times higher likelihood of going to the ED and a 2.46 (95% CI 1.97, 3.19) times higher likelihood of hospitalization than the overweight and normal-weight groups. Asthma severity was a significant predictor of overall QOL (beta = -23.737, p = .002). CONCLUSIONS: The study results are consistent with other investigations that demonstrate that obese persons are at higher risk of experiencing severe asthma symptoms and support obesity as a potentially modifiable risk factor for asthma mitigation and prevention. PMID- 26874458 TI - Genetic and morphological consequences of Quaternary glaciations: A relic barbel lineage (Luciobarbus pallaryi, Cyprinidae) of Guir Basin (Algeria). AB - Climatic variations during the Quaternary period had a considerable impact on landscapes and habitat fragmentation (rivers) in North Africa. These historical events can have significant consequences on the genetic structure of the populations. Indeed, geographically separated and genetically isolated populations tend to differentiate themselves through time, eventually becoming distinct lineages, allowing new species to emerge in later generations. The aim of the present study is to use genetic and morphological techniques to evaluate the major role of the Saalian glaciation (Middle Quaternary) in the establishment of the geographic space and in the evolution of the intraspecific genetic diversity, by tracing the demographic history of barbels belonging to the Luciobarbus pallaryi (Cyprinidae) species in the Guir Basin (Algeria). In this context, two populations, from two distinct and isolated sites, were studied. Analysis of the cytochrome b (cyt b) mitochondrial markers and of the "D-loop" control region has shown that the "upstream" and "downstream" Guir populations are genetically differentiated. The molecular analyses suggest that the upstream population was disconnected from this hydrographic system during the Saalian glaciation period of the Quaternary. Subsequently, it was isolated in the foggaras underground waters in the Great Western Erg, at approximately 320 000 years BP, creating, through a bottleneck effect, a new allopatric lineage referred to as "Adrar". Conversely, the high genetic diversity in the upstream Guir (Bechar) population suggests that the stock is globally in expansion. These barbels (n=52) were also examined with meristic, morphometric, osteological, and biological features. These data also reveal a complete discrimination between the two populations, with a remarkable and distinctive behavioural adaptation for the Adrar specimens: neoteny. PMID- 26874459 TI - SSRs transferability and genetic diversity of three allogamous ryegrass species. AB - Simple sequence repeat (SSR) markers are widely applied in studies of plant molecular genetics due to their abundance in the genome, codominant nature, and high repeatability. However, microsatellites are not always available for the species to be studied and their isolation could be time- and cost-consuming. To investigate transferability in cross-species applications, 102 primer pairs previously developed in ryegrass and tall fescue were amplified across three allogamous ryegrass species including Lolium rigidum, Lolium perenne and Lolium multiflorum. Their highly transferability (100%) were evidenced. While, most of these markers were multiple loci, only 17 loci were selected for a robust, single locus pattern, which may be due to the recentness of the genome duplication or duplicated genomic regions, as well as speciation. A total of 87 alleles were generated with an average of 5.1 per locus. The mean polymorphism information content (PIC) and observed heterozygosity (Ho) values at genus was 0.5532 and 0.5423, respectively. Besides, analysis of molecular variance (AMOVA) revealed that all three levels contributed significantly to the overall genetic variation, with the species level contributing the least (P<0.001). Also, the unweighted pair group method with arithmetic averaging dendrogram (UPGMA), Bayesian model based STRUCTURE analysis and the principal coordinate analysis (PCoA) showed that accessions within species always tended to the same cluster firstly and then to related species. The results showed that these markers developed in related species are transferable efficiently across species, and likely to be useful in analyzing genetic diversity. PMID- 26874460 TI - Stability and Marginal Bone Level Changes of SLActive Titanium-Zirconium Implants Placed with Flapless Surgery: A Prospective Pilot Study. AB - BACKGROUND: Immediately-loaded, narrow-diameter implants can be a less invasive alternative for the implant-supported fixed rehabilitation of narrow, posterior crests. PURPOSE: To determine the stability and marginal bone level (MBL) changes of narrow-diameter, titanium-zirconium (TiZr) implants placed with flapless surgery and loaded immediately in the posterior region. MATERIALS AND METHODS: Thirty-eight TiZr implants (3.3 mm diameter, 10 mm length, Roxolid, Straumann AG) were placed in the posterior crests of 14 patients with computer-guided flapless surgery as a support of 3-unit posterior bridges. Eighteen implants were loaded immediately, and 20 implants were loaded conventionally. The implant stability quotients were determined at the 1, 2, 4, and 8. weeks of healing before conventional loading, and at the 3, 6, and 12. months after loading by resonance frequency analysis. The MBL changes were measured by digital radiography. RESULTS: The surgical protocols were accomplished without any biological complications. There was no significant difference in the stability changes of TiZr implants between the loading groups (p > .05). The MBL changes were -0.18 +/ 0.27 mm and -0.24 +/- 0.27 mm at the 12. month of immediate and conventional loading, respectively, which was not statistically significant (p > .05). CONCLUSION: The stability and MBL changes of TiZr implants supporting posterior 3 unit bridges were clinically acceptable at the first year of loading. PMID- 26874461 TI - Recreational marijuana use and acute ischemic stroke: A population-based analysis of hospitalized patients in the United States. AB - BACKGROUND: Recreational marijuana use is considered to have few adverse effects. However, recent evidence has suggested that it precipitates cardiovascular and cerebrovascular events. Here, we investigated the relationship between marijuana use and hospitalization for acute ischemic stroke (AIS) using data from the largest inpatient database in the United States. METHODS: The Nationwide Inpatient Sample was queried from 2004 to 2011 for all patients (age 15-54) with a primary diagnosis of AIS. The incidence of AIS hospitalization in marijuana users and non-marijuana users was determined. We utilized multivariable logistic regression analyses to study the independent association between marijuana use and AIS. RESULTS: Overall, the incidence of AIS was significantly greater among marijuana users compared to non-users (Relative Risk [RR]: 1.13, 95% CI: 1.11 1.15, P<0.0001) and had the greatest difference in the 25-34 age group (RR: 2.26, 95% CI: 2.13-2.38, P<0.0001). Marijuana use was more prevalent among younger patients, males, African Americans, and Medicaid enrollees (P<0.0001). Marijuana users were more likely to use other illicit substances but had less overall medical comorbidity. In multivariable analysis, adjusted for potential confounders, marijuana (Odds Ratio [OR]: 1.17, 95% CI: 1.15-1.20), tobacco (OR: 1.76, 95% CI: 1.74-1.77), cocaine (OR: 1.32, 95% CI: 1.30-1.34), and amphetamine (OR: 2.21, 95% CI: 2.12-2.30) usage were found to increase the likelihood of AIS (all P<0.0001). CONCLUSION: Among younger adults, recreational marijuana use is independently associated with 17% increased likelihood of AIS hospitalization. PMID- 26874462 TI - BCOR internal tandem duplications in clear cell sarcoma of the kidney. PMID- 26874463 TI - Differential prevalence and demographic and clinical correlates of second generation antipsychotic use in bipolar I versus bipolar II disorder. AB - AIMS: To assess second-generation antipsychotic (SGA) use, demographics, and clinical correlates in patients with bipolar I disorder (BDI) versus bipolar II disorder (BDII). METHODS: Stanford Bipolar Disorder (BD) Clinic outpatients enrolled during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Current SGA use, demographics, and clinical correlates were assessed for BDI versus BDII. RESULTS: Among 503 BD outpatients, in BDI versus BDII, SGA use was more than twice as common (44.0% versus 21.2%), and doses were approximately twice as high. BDI patients taking (N = 107) versus not taking (N = 136) SGAs less often had current full time employment and college degree; and more often had lifetime psychiatric hospitalization, current depression, and current complex pharmacotherapy, and had a higher mean current Clinical Global Impression for Bipolar Version Overall Severity score, and these persisted significantly after covarying for employment and education. Prior psychiatric hospitalization was the most robust correlate of SGA use in BDI patients. In contrast, these demographic and clinical correlates of SGA use were not statistically significant among patients with BDII, although BDII (but not BDI) patients taking (N = 55) versus not taking (N = 205) SGAs were more likely to have current mood stabilizer use (67.3% versus 51.7%). LIMITATIONS: American tertiary bipolar disorder clinic referral sample, cross sectional design. CONCLUSIONS: Current SGA use was robustly associated with prior psychiatric hospitalization in BDI and to a more limited extent with current mood stabilizer use in BDII. SGA use associations with other unfavorable illness characteristics in BDI were less robust. PMID- 26874465 TI - Description of Lecythium terrestris sp. nov. (Chlamydophryidae, Cercozoa), a Soil Dwelling Protist Feeding on Fungi and Algae. AB - Testate amoebae have been frequently studied by protistologists, but still little information is available on some groups like the Chlamydophryidae. These amoebae are difficult to culture and therefore quantitative information on their morphology, phylogeny and ecology is scarce. We isolated and cultured a small testate amoeba from an agricultural field at Muncheberg near Berlin, Germany. Morphological analyses revealed it to be a new species of the genus Lecythium. We describe Lecythium terrestris sp. nov. and present its morphology, mycophagous and algivorous feeding habits and its ability to form cell aggregates by fusion. Using small-subunit ribosomal RNA gene phylogeny, we could confirm the phylogenetic position of the genus Lecythium among the Cercozoa where it groups closely to Pseudodifflugiidae (Tectofilosida). PMID- 26874464 TI - Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination. AB - N-myc & STAT Interactor, NMI, is a protein that has mostly been studied for its physical interactions with transcription factors that play critical roles in tumor growth, progression and metastasis. NMI is an inducible protein, thus its intracellular levels and location can vary dramatically, influencing a diverse array of cellular functions in a context-dependent manner. The physical interactions of NMI with its binding partners have been linked to many aspects of tumor biology including DNA damage response, cell death, epithelial-to mesenchymal transition and stemness. Thus, discovering more details about the function(s) of NMI could reveal key insights into how transcription factors like c-Myc, STATs and BRCA1 are contextually regulated. Although a normal, physiological function of NMI has not yet been discovered, it has potential roles in pathologies ranging from viral infection to cancer. This review provides a timely perspective of the unfolding roles of NMI with specific focus on cancer progression and metastasis. PMID- 26874466 TI - Chimeric antigen receptor T cell treatment in hematologic malignancies. AB - Adoptive transfer of T cells that have genetically engineered chimeric antigen receptors (CARs) is an encouraging treatment modality in the hematological malignancies. These T cells are capable of selectively recognizing tumor associated antigens. There are a variety of reported, as well as ongoing studies on the utilization of CAR-T cells in the treatment of leukemia, myeloma, as well as B and T cell lymphomas. In this review, we aimed to highlight current understanding of this promising treatment modality, including its efficacy and adverse effects. PMID- 26874467 TI - Priority needs and wisdom strategy for blood transfusion safety in developing low resource countries. AB - OBJECTIVE: To evaluate the implementation of alternative safety measures that reduce the risk of transfusion transmissible infections as an affordable measure in low resource countries. BACKGROUND: It is still difficult in developing countries with limited resources to mandate nucleic acid testing due to its high cost. Although NAT reduces the window period of infection, the developing countries are still in need of an efficient and effective transfusion programme before implementing the complex high cost NAT. STUDY DESIGN AND METHODS: Two thousand eight hundred eighty sero-negative first-time and repeat donations from Fayoum University Hospital blood bank were individually analysed by NAT for HIV, HBV and HCV. Only discriminatory-positive NAT were classified comparing the non remunerated and family replacement donations. RESULTS: Significant discriminatory positive differences were observed for HBV NAT results, 2 remunerated donations compared to 0 non-remunerated sero-negative donations. The discriminatory positive differences were also significant for HCV NAT results, 4 remunerated donations compared to 1 non-remunerated sero-negative donation. No sero-negative, discriminatory-positive NAT HIV case was found. Seven out of 8 discriminatory positive cases were from first time donations. CONCLUSION: In order to ensure blood safety, the recruitment and retention of voluntary, non-remunerated repeat donors should be a major commitment for low resource countries in which NAT implementation is costly and not feasible. PMID- 26874468 TI - Patient-derived xenografts as tools in pharmaceutical development. AB - Successful drug development in oncology is grossly suboptimal, manifested by the very low percentage of new agents being developed that ultimately succeed in clinical approval. This poor success is in part due to the inability of standard cell-line xenograft models to accurately predict clinical success and to tailor chemotherapy specifically to a group of patients more likely to benefit from the therapy. Patient-derived xenografts (PDXs) maintain the histopathological architecture and molecular features of human tumors, and offer a potential solution to maximize drug development success and ultimately generate better outcomes for patients. Although imperfect in mimicking all aspects of human cancer, PDXs are a more predictable platform for preclinical evaluation of treatment effect and in selected cases can guide therapeutic decision making in the clinic. This article summarizes the current status of PDX models, challenges associated with modeling human cancer, and various approaches that have been applied to overcome these challenges and improve the clinical relevance of PDX cancer models. PMID- 26874469 TI - Developing LED UV fluorescence sensors for online monitoring DOM and predicting DBPs formation potential during water treatment. AB - Online monitoring dissolved organic matter (DOM) is urgent for water treatment management. In this study, high performance size exclusion chromatography with multi-UV absorbance and multi-emission fluorescence scans were applied to spectrally characterize samples from 16 drinking water sources across Yangzi River and Huai River Watersheds. The UV absorbance indices at 254 nm and 280 nm referred to the same DOM components and concentration, and the 280 nm UV light could excite both protein-like and humic-like fluorescence. Hence a novel UV fluorescence sensor was developed out using only one UV280 light-emitting diode (LED) as light source. For all samples, enhanced coagulation was mainly effective for large molecular weight biopolymers; while anion exchange further substantially removed humic substances. During chlorination tests, UVA280 and UVA254 showed similar correlations with yields of disinfection byproducts (DBPs); the humic-like fluorescence obtained from LED sensors correlated well with both trihalomethanes and haloacetic acids yields, while the correlation between protein-like fluorescence and trihalomethanes was relatively poor. Anion exchange exhibited more reduction of DBPs yields as well as UV absorbance and fluorescence signals than enhanced coagulation. The results suggest that the LED UV fluorescence sensors are very promising for online monitoring DOM and predicting DBPs formation potential during water treatment. PMID- 26874470 TI - Investigation of severe UF membrane fouling induced by three marine algal species. AB - Reducing membrane fouling caused by seawater algal bloom is a challenge for regions of the world where most of their freshwater is produced by seawater desalination. This study aims to compare ultrafiltration (UF) fouling potential of three ubiquitous marine algal species cultures (i.e., Skeletonema costatum SKC, Tetraselmis sp.-TET, and Hymenomonas sp.-HYM) sampled at different phases of growth. Results showed that flux reduction and irreversible fouling were more severe during the decline phase as compared to the exponential phase, for all species. SKC and TET were responsible for substantial irreversible fouling but their impact was significantly lower than HYM. The development of a transparent gel layer surrounding the cell during the HYM growth and accumulating in water is certainly responsible for the more severe observed fouling. Chemical backwash with a standard chlorine solution did not recover any membrane permeability. For TET and HYM, the Hydraulically Irreversible Fouling Index (HIFI) was correlated to their biopolymer content but this correlation is specific for each species. Solution pre-filtration through a 1.2 MUm membrane proved that cells and particulate algal organic matter (p-AOM) considerably contribute to fouling, especially for HYM for which the HIFI was reduced by a factor of 82.3. PMID- 26874471 TI - Toward the neural implementation of structure learning. AB - Despite significant advances in neuroscience, the neural bases of intelligence remain poorly understood. Arguably the most elusive aspect of intelligence is the ability to make robust inferences that go far beyond one's experience. Animals categorize objects, learn to vocalize and may even estimate causal relationships all in the face of data that is often ambiguous and sparse. Such inductive leaps are thought to result from the brain's ability to infer latent structure that governs the environment. However, we know little about the neural computations that underlie this ability. Recent advances in developing computational frameworks that can support efficient structure learning and inductive inference may provide insight into the underlying component processes and help pave the path for uncovering their neural implementation. PMID- 26874472 TI - Quantifying collectivity. AB - In biological function emerges from the interactions of components with only partially aligned interests. An example is the brain-a large aggregation of neurons capable of producing unitary, coherent output. A theory for how such aggregations produce coherent output remains elusive. A first question we might ask is how collective is the behavior of the components? Here we introduce two properties of collectivity and illustrate how these properties can be quantified using approaches from information theory and statistical physics. First, amplification quantifies the sensitivity of the large scale to information at the small scale and is related to the notion of criticality in statistical physics. Second, decomposability reveals the extent to which aggregate behavior is reducible to individual contributions or is the result of synergistic interactions among components forming larger subgroups. These measures facilitate identification of causally important components and subgroups that might be experimentally manipulated to study the evolution and controllability of biological circuits and their outputs. PMID- 26874474 TI - Communication: Isotopic effects on tunneling motions in the water trimer. AB - We present results of ring polymer molecular dynamics simulations that shed light on the effects of nuclear quantum fluctuations on tunneling motions in cyclic [H2O]3 and [D2O]3, at the representative temperature of T = 75 K. In particular, we focus attention on free energies associated with two key isomerization processes: The first one corresponds to flipping transitions of dangling OH bonds, between up and down positions with respect to the O-O-O plane of the cluster; the second involves the interchange between connecting and dangling hydrogen bond character of the H-atoms in a tagged water molecule. Zero point energy and tunneling effects lead to sensible reductions of the free energy barriers. Due to the lighter nature of the H nuclei, these modifications are more marked in [H2O]3 than in [D2O]3. Estimates of the characteristic time scales describing the flipping transitions are consistent with those predicted based on standard transition-state-approximation arguments. PMID- 26874473 TI - Perspective: Computer simulations of long time dynamics. AB - Atomically detailed computer simulations of complex molecular events attracted the imagination of many researchers in the field as providing comprehensive information on chemical, biological, and physical processes. However, one of the greatest limitations of these simulations is of time scales. The physical time scales accessible to straightforward simulations are too short to address many interesting and important molecular events. In the last decade significant advances were made in different directions (theory, software, and hardware) that significantly expand the capabilities and accuracies of these techniques. This perspective describes and critically examines some of these advances. PMID- 26874475 TI - Communication: Real time observation of unimolecular decay of Criegee intermediates to OH radical products. AB - In the atmosphere, a dominant loss process for carbonyl oxide intermediates produced from alkene ozonolysis is also an important source of hydroxyl radicals. The rate of appearance of OH radicals is revealed through direct time-domain measurements following vibrational activation of prototypical methyl-substituted Criegee intermediates under collision-free conditions. Complementary theoretical calculations predict the unimolecular decay rate for the Criegee intermediates in the vicinity of the barrier for 1,4 hydrogen transfer that leads to OH products. Both experiment and theory yield unimolecular decay rates of ca. 10(8) and 10(7) s(-1) for syn-CH3CHOO and (CH3)2COO, respectively, at energies near the barrier. Tunneling through the barrier, computed from high level electronic structure theory and experimentally validated, makes a significant contribution to the decay rate. Extension to thermally averaged unimolecular decay of stabilized Criegee intermediates under atmospheric conditions yields rates that are six orders of magnitude slower than those evaluated directly in the barrier region. PMID- 26874476 TI - A simple approach to the state-specific MR-CC using the intermediate Hamiltonian formalism. AB - This paper presents a rigorous state-specific multi-reference coupled cluster formulation of the method first proposed by Meller et al. [J. Chem. Phys. 104, 4068 (1996)]. Guess values of the amplitudes of the single and double excitations (the T operator) on the top of the references are extracted from the knowledge of the coefficients of the Multi-Reference Singles and Doubles Configuration Interaction (MR-CISD) matrix. The multiple parentage problem is solved by scaling these amplitudes from the interaction between the references and the singles and doubles. Then one proceeds to a dressing of the MR-CISD matrix under the effect of the triples and quadruples, the coefficients of which are estimated from the action of exp(T). This dressing follows the logic of the intermediate effective Hamiltonian formalism. The dressed MR-CISD matrix is diagonalized and the process is iterated to convergence. As a simplification, the coefficients of the triples and quadruples may in practice be calculated from the action of T(2) only, introducing 5th-order differences in the energies. The so-simplified method is tested on a series of benchmark systems from Complete Active Spaces (CASs) involving 2-6 active electrons up to bond breakings. The comparison with full configuration interaction results shows that the errors are of the order of a few millihartree, five times smaller than those of the CAS-CISD, and the deviation to strict separability is lower than 10 MU hartree. The method is totally uncontracted, parallelizable, and extremely flexible since it may be applied to selected MR and/or selected CISD. Some potential generalizations are briefly discussed. PMID- 26874477 TI - A time-dependent formulation of multi-reference perturbation theory. AB - We discuss the time-dependent formulation of perturbation theory in the context of the interacting zeroth-order Hamiltonians that appear in multi-reference situations. As an example, we present a time-dependent formulation and implementation of second-order n-electron valence perturbation theory. The resulting time-dependent n-electron valence second-order perturbation theory (t NEVPT2) method yields the fully uncontracted n-electron valence perturbation wavefunction and energy, but has a lower computational scaling than the usual contracted variants, and also avoids the construction of high-order density matrices and the diagonalization of metrics. We present results of t-NEVPT2 for the water, nitrogen, carbon, and chromium molecules and outline directions for the future. PMID- 26874478 TI - A view on coupled cluster perturbation theory using a bivariational Lagrangian formulation. AB - We consider two distinct coupled cluster (CC) perturbation series that both expand the difference between the energies of the CCSD (CC with single and double excitations) and CCSDT (CC with single, double, and triple excitations) models in orders of the Moller-Plesset fluctuation potential. We initially introduce the E CCSD(T-n) series, in which the CCSD amplitude equations are satisfied at the expansion point, and compare it to the recently developed CCSD(T-n) series [J. J. Eriksen et al., J. Chem. Phys. 140, 064108 (2014)], in which not only the CCSD amplitude, but also the CCSD multiplier equations are satisfied at the expansion point. The computational scaling is similar for the two series, and both are term wise size extensive with a formal convergence towards the CCSDT target energy. However, the two series are different, and the CCSD(T-n) series is found to exhibit a more rapid convergence up through the series, which we trace back to the fact that more information at the expansion point is utilized than for the E CCSD(T-n) series. The present analysis can be generalized to any perturbation expansion representing the difference between a parent CC model and a higher level target CC model. In general, we demonstrate that, whenever the parent parameters depend upon the perturbation operator, a perturbation expansion of the CC energy (where only parent amplitudes are used) differs from a perturbation expansion of the CC Lagrangian (where both parent amplitudes and parent multipliers are used). For the latter case, the bivariational Lagrangian formulation becomes more than a convenient mathematical tool, since it facilitates a different and faster convergent perturbation series than the simpler energy-based expansion. PMID- 26874479 TI - A reactant-coordinate-based wave packet method for full-dimensional state-to state quantum dynamics of tetra-atomic reactions: Application to both the abstraction and exchange channels in the H + H2O reaction. AB - An efficient and accurate wave packet method is proposed for the calculation of the state-to-state S-matrix elements in bimolecular reactions involving four atoms. This approach propagates an initial state specific wave packet in reactant Jacobi coordinates. The projection in product channels is carried out on projection planes, which have one less degree of freedom, by transforming both the time-dependent wave packet and final product states into a set of intermediate coordinates. This reactant-coordinate-based method is more efficient than product-coordinate-based methods because it typically requires a smaller number of basis functions or grid points and allows the determination of S-matrix elements for multiple product channels from a single propagation. This method is demonstrated in calculating the (Jtot = 0) state-to-state S-matrix elements for both the abstraction and exchange channels of the H + H2O reaction. PMID- 26874480 TI - From dimers to collective dipoles: Structure and dynamics of methanol/ethanol partition by narrow carbon nanotubes. AB - Alcohol partitioning by narrow single-walled carbon nanotubes (SWCNTs) holds the promise for the development of novel nanodevices for diverse applications. Consequently, in this work, the partition of small alcohols by narrow tubes was kinetically and structurally quantified via molecular dynamics simulations. Alcohol partitioning is a fast process in the order of 10 ns for diluted solutions but the axial-diffusivity within SWCNT is greatly diminished being two to three orders of magnitude lower with respect to bulk conditions. Structurally, alcohols form a single-file conformation under confinement and more interestingly, they exhibit a pore-width dependent transition from dipole dimers to a single collective dipole, for both methanol and ethanol. Energetic analyses demonstrate that this transition is the result of a detailed balance between dispersion and electrostatics interactions, with the latter being more pronounced for collective dipoles. This transition fully modifies the reorientational dynamics of the loaded particles, generating stable collective dipoles that could find usage in signal-amplification devices. Overall, the results herein have shown distinct physico-chemical features of confined alcohols and are a further step towards the understanding and development of novel nanofluidics within SWCNTs. PMID- 26874481 TI - Comparison of simplified sum-over-state expressions to calculate resonance Raman intensities including Franck-Condon and Herzberg-Teller effects. AB - Sum-over-state (SOS) expressions to simulate absorption spectroscopy and resonance Raman (RR) scattering including Franck-Condon (FC) and Herzberg-Teller (HT) effects are described. Starting from the general SOS method, several simplified SOS formulae are derived. In particular, within the so-called independent mode displaced harmonic oscillator model, it is shown that including the vibronic structure in the absorption and RR spectra only requires the calculation of FC overlap integrals of the type thetag0|thetaev, where g, e, and v stand for the electronic ground state, excited state, and vibrational quantum number, respectively. Additionally, an approximation of the latter approach is introduced, referred as the simplified Phie method, in which the FC factors are neglected. This method is advantageous from the computational point of view and it is demonstrated that it reproduces the main characteristics of the more involved approaches. The merits and drawbacks of the different methods are discussed by applying them to the prototypical compound of Rhodamine 6G. Overall, this work intends to unravel and clarify some differences in the SOS theories of RR scattering. PMID- 26874482 TI - Study of infrared emission spectroscopy for the B(1)Deltag-A(1)Piu and B'(1)Sigmag(+)-A(1)Piu systems of C2. AB - Thirteen bands for the B(1)Deltag-A(1)Piu system and eleven bands for the B'(1)Sigmag(+)-A(1)Piu system of C2 were identified in the Fourier transform infrared emission spectra of hydrocarbon discharges. The B'(1)Sigmag(+)v = 4 and the B(1)Deltag v = 6, 7, and 8 vibrational levels involved in nine bands were studied for the first time. A direct global analysis with Dunham parameters was carried out satisfactorily for the B(1)Deltag-A(1)Piu system except for a small perturbation in the B(1)Deltag v = 6 level. The calculated rovibrational term energies up to B(1)Deltag v = 12 showed that the level crossing between the B(1)Deltag and d(3)Pig states is responsible for many of the prominent perturbations in the Swan system observed previously. Nineteen forbidden transitions of the B(1)Deltag-a(3)Piu transition were identified and the off diagonal spin-orbit interaction constant AdB between d(3)Pig and B(1)Deltag was derived as 8.3(1) cm(-1). For the B'(1)Sigmag(+)-A(1)Piu system, only individual band analyses for each vibrational level in the B'(1)Sigmag(+) state could be done satisfactorily and Dunham parameters obtained from these effective parameters showed that the anharmonic vibrational constant omegaexe is anomalously small (nearly zero). Inspection of the RKR (Rydberg-Klein-Rees) potential curves for the B'(1)Sigmag(+) and X(1)Sigmag(+) states revealed that an avoided crossing or nearly avoided crossing may occur around 30,000 cm(-1), which is responsible for the anomalous molecular constants in these two states. PMID- 26874483 TI - Molecular dynamics and simulations study on the vibrational and electronic solvatochromism of benzophenone. AB - Solvent plays a key role in diverse physico-chemical and biological processes. Therefore, understanding solute-solvent interactions at the molecular level of detail is of utmost importance. A comprehensive solvatochromic analysis of benzophenone (Bzp) was carried out in various solvents using Raman and electronic spectroscopy, in conjunction with Density Functional Theory (DFT) calculations of supramolecular solute-solvent clusters generated using classical Molecular Dynamics Simulations (c-MDSs). The >C=O stretching frequency undergoes a bathochromic shift with solvent polarity. Interestingly, in protic solvents this peak appears as a doublet: c-MDS and ad hoc explicit solvent ab initio calculations suggest that the lower and higher frequency peaks are associated with the hydrogen bonded and dangling carbonyl group of Bzp, respectively. Additionally, the dangling carbonyl in methanol (MeOH) solvent is 4 cm(-1) blue shifted relative to acetonitrile solvent, despite their similar dipolarity/polarizability. This suggests that the cybotactic region of the dangling carbonyl group in MeOH is very different from its bulk solvent structure. Therefore, we propose that this blue-shift of the dangling carbonyl originates in the hydrophobic solvation shell around it resulting from extended hydrogen bonding network of the protic solvents. Furthermore, the 1(1)npi(*) (band I) and 1(1)pipi(*) (band II) electronic transitions show a hypsochromic and bathochromic shift, respectively. In particular, these shifts in protic solvents are due to differences in their excited state-hydrogen bonding mechanisms. Additionally, a linear relationship is obtained for band I and the >C=O stretching frequency (cm(-1)), which suggests that the different excitation wavelengths in band I correspond to different solvation states. Therefore, we hypothesize that the variation in excitation wavelengths in band I could arise from different solvation states leading to varying solvation dynamics. This will have implications for ultrafast processes associated with electron-transfer, charge transfer, and also the photophysical aspects of excited states. PMID- 26874484 TI - Charged vanadium-benzene multidecker clusters: DFT and quantum Monte Carlo study. AB - Using explicitly correlated fixed-node quantum Monte Carlo and density functional theory (DFT) methods, we study electronic properties, ground-state multiplets, ionization potentials, electron affinities, and low-energy fragmentation channels of charged half-sandwich and multidecker vanadium-benzene systems with up to 3 vanadium atoms, including both anions and cations. It is shown that, particularly in anions, electronic correlations play a crucial role; these effects are not systematically captured with any commonly used DFT functionals such as gradient corrected, hybrids, and range-separated hybrids. On the other hand, tightly bound cations can be described qualitatively by DFT. A comparison of DFT and quantum Monte Carlo provides an in-depth understanding of the electronic structure and properties of these correlated systems. The calculations also serve as a benchmark study of 3d molecular anions that require a balanced many-body description of correlations at both short- and long-range distances. PMID- 26874485 TI - Multiple product pathways in photodissociation of nitromethane at 213 nm. AB - In this paper, we present a photodissociation dynamics study of nitromethane at 213 nm in the pi -> pi(*) transition. Resonantly enhanced multiphoton ionization spectroscopy and ion-imaging were applied to measure the internal state distributions and state-resolved scattering distributions of the CH3, NO(X (2)Pi, A (2)Sigma(+)), and O((3)PJ) photofragments. The rotationally state-resolved scattering distribution of the CH3 fragment showed two velocity components, of which the slower one decreased the relative intensity as the rotational and vibrational excitations. The translational energy distribution of the faster CH3 fragment indicated the production of the NO2 counter-product in the electronic excited state, wherein 1 (2)B2 was the most probable. The NO(v = 0) fragment exhibited a bimodal translational energy distribution, whereas the NO(v = 1 and 2) fragment exhibited a single translational energy component with a relatively larger internal energy. The translational energy of a portion of the O((3)PJ) photofragment was found to be higher than the one-photon dissociation threshold, indicating the two-photon process involved. The NO(A (2)Sigma(+)) fragment, which was detected by ionization spectroscopy via the Rydberg <- A (2)Sigma(+) transition, also required two-photon energy. These experimental data corroborate the existence of competing photodissociation product pathways, CH3 + NO2,CH3 + NO + O,CH3O + NO, and CH3NO + O, following the pi -> pi(*) transition. The origins of the observed photofragments are discussed in this report along with recent theoretical studies and previous dynamics experiments performed at 193 nm. PMID- 26874486 TI - Quantum cluster equilibrium model of N-methylformamide-water binary mixtures. AB - The established quantum cluster equilibrium (QCE) approach is refined and applied to N-methylformamide (NMF) and its aqueous solution. The QCE method is split into two iterative cycles: one which converges to the liquid phase solution of the QCE equations and another which yields the gas phase. By comparing Gibbs energies, the thermodynamically stable phase at a given temperature and pressure is then chosen. The new methodology avoids metastable solutions and allows a different treatment of the mean-field interactions within the gas and liquid phases. These changes are of crucial importance for the treatment of binary mixtures. For the first time in a QCE study, the cis-trans-isomerism of a species (NMF) is explicitly considered. Cluster geometries and frequencies are calculated using density functional theory (DFT) and complementary coupled cluster single point energies are used to benchmark the DFT results. Independent of the selected quantum-chemical method, a large set of clusters is required for an accurate thermodynamic description of the binary mixture. The liquid phase of neat NMF is found to be dominated by the cyclic trans-NMF pentamer, which can be interpreted as a linear trimer that is stabilized by explicit solvation of two further NMF molecules. This cluster reflects the known hydrogen bond network preferences of neat NMF. PMID- 26874487 TI - Extracting conformational information from single molecule photon statistics. AB - In this paper, we describe the approach of resonant trajectories of photon emission (Traj and TrajQ) in the conformational coordinate X and external field frequency omegaL space to extract the conformational information of single molecule. The Smoluchowski equation is employed to describe the conformational dynamics of the single molecule in complex environments. This approach is applied to single Thioflavin T (ThT) molecule, and our results are in excellent agreement with the results of ab initio simulations. PMID- 26874489 TI - A new method to induce molecular low bias negative differential resistance with multi-peaks. AB - According to a first-principles study of the transport properties of two thiolated anthracene-9,10-diono molecules sandwiching ethyl, a new method to induce molecular low bias negative differential resistance with multi-peaks for strong n- or p-type molecules is proposed. The anthracene-9,10-diono molecule shows strong n-type characteristics when in contact with Au and Ag electrodes via a thiolate. The multiple negative differential resistance effect originated from the molecule-electrode couple is different between Ag and Au electrodes. Our investigations may promise potential for applications in molecular devices with low power dissipation and multifunction in the future. PMID- 26874488 TI - Observation and characterization of the smallest borospherene, B28(-) and B28. AB - Free-standing boron nanocages or borospherenes have been observed recently for B40(-) and B40. There is evidence that a family of borospherenes may exist. However, the smallest borospherene is still not known. Here, we report experimental and computational evidence of a seashell-like borospherene cage for B28(-) and B28. Photoelectron spectrum of B28(-) indicated contributions from different isomers. Theoretical calculations showed that the seashell-like B28(-) borospherene is competing for the global minimum with a planar isomer and it is shown to be present in the cluster beam, contributing to the observed photoelectron spectrum. The seashell structure is found to be the global minimum for neutral B28 and the B28(-) cage represents the smallest borospherene observed to date. It is composed of two triangular close-packed B15 sheets, interconnected via the three corners by sharing two boron atoms. The B28 borospherene was found to obey the 2(n + 1)(2) electron-counting rule for spherical aromaticity. PMID- 26874490 TI - The Jahn-Teller plus pseudo-Jahn-Teller vibronic problem in the C3 radical and its topological implications. AB - The combined Jahn-Teller plus pseudo-Jahn-Teller [(E'+A1')?e'] problem is discussed for the tricarbon radical (C3) by means of ab initio calculations at the multireference configuration interaction level of theory. For the (1)E' electronic state arising from a e'(2) valence configuration, three additional symmetry-equivalent C2v seams are found to lie in close proximity to the D3h symmetry-required seam over the entire range of the breathing coordinate here considered. As the perimeter of the molecule increases, the C2v disjoint seams approach the D3h one almost linearly and ultimately coalesce with it at Q1 = 5.005 a0, thence forming an intersection node or confluence. By further increasing the size of the molecular triangle, the C2v seams get rotated by +/-pi in the g-h plane. A three-state vibronic Hamiltonian is also proposed to model locally the title system and shown to accurately mimic the calculated data over the region close to the minimum energy crossing point. No net geometric phase effect is observed when the associated electronic wave functions are adiabatically transported along closed paths encircling the four singularity points. For all paths enclosing the intersection node, the sign reversal criterion is shown to be not fulfilled, even for infinitesimal loops. The results so obtained are expected to be valid for other ring systems experiencing similar topological attributes. PMID- 26874491 TI - Characteristics of energy exchange between inter- and intramolecular degrees of freedom in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with implications for coarse-grained simulations of shock waves in polyatomic molecular crystals. AB - In this report, we characterize the kinetics and dynamics of energy exchange between intramolecular and intermolecular degrees of freedom (DoF) in crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). All-atom molecular dynamics (MD) simulations are used to obtain predictions for relaxation from certain limiting initial distributions of energy between the intra- and intermolecular DoF. The results are used to parameterize a coarse-grained Dissipative Particle Dynamics at constant Energy (DPDE) model for TATB. Each TATB molecule in the DPDE model is represented as an all-atom, rigid-molecule mesoparticle, with explicit external (molecular translational and rotational) DoF and coarse-grained implicit internal (vibrational) DoF. In addition to conserving linear and angular momentum, the DPDE equations of motion conserve the total system energy provided that particles can exchange energy between their external and internal DoF. The internal temperature of a TATB molecule is calculated using an internal equation of state, which we develop here, and the temperatures of the external and internal DoF are coupled using a fluctuation-dissipation relation. The DPDE force expression requires specification of the input parameter sigma that determines the rate at which energy is exchanged between external and internal DoF. We adjusted sigma based on the predictions for relaxation processes obtained from MD simulations. The parameterized DPDE model was employed in large-scale simulations of shock compression of TATB. We show that the rate of energy exchange governed by sigma can significantly influence the transient behavior of the system behind the shock. PMID- 26874492 TI - On the structure of crystalline and molten cryolite: Insights from the ab initio molecular dynamics in NpT ensemble. AB - Ab initio molecular dynamics simulations in isobaric-isothermal ensemble have been performed to study the low- and the high-temperature crystalline and liquid phases of cryolite. The temperature induced transitions from the low-temperature solid (alpha) to the high-temperature solid phase (beta) and from the phase beta to the liquid phase have been simulated using a series of MD runs performed at gradually increasing temperature. The structure of crystalline and liquid phases is analysed in detail and our computational approach is shown to reliably reproduce the available experimental data for a wide range of temperatures. Relatively frequent reorientations of the AlF6 octahedra observed in our simulation of the phase beta explain the thermal disorder in positions of the F( ) ions observed in X-ray diffraction experiments. The isolated AlF6(3-), AlF5(2 ), AlF4(-), as well as the bridged Al2Fm(6-m) ionic entities have been identified as the main constituents of cryolite melt. In accord with the previous high temperature NMR and Raman spectroscopic experiments, the compound AlF5(2-) has been shown to be the most abundant Al-containing species formed in the melt. The characteristic vibrational frequencies for the AlFn(3-n) species in realistic environment have been determined and the computed values have been found to be in a good agreement with experiment. PMID- 26874493 TI - Local structure, composition, and crystallization mechanism of a model two-phase "composite nanoglass". AB - We report a detailed study of the local composition and structure of a model, bi phasic nanoglass with nominal stoichiometry Cu55Nb45. Three dimensional atom probe data suggest a nanoscale-phase-separated glassy structure having well defined Cu-rich and Nb-rich regions with a characteristic length scale of ~ 3 nm. However, extended x-ray absorption fine structure analysis indicates subtle differences in the local environments of Cu and Nb. While the Cu atoms displayed a strong tendency to cluster and negligible structural order beyond the first coordination shell, the Nb atoms had a larger fraction of unlike neighbors (higher chemical order) and a distinctly better-ordered structural environment (higher topological order). This provides the first experimental indication that metallic glass formation may occur due to frustration arising from the competition between chemical ordering and clustering. These observations are complemented by classical as well as ab initio molecular dynamics simulations. Our study indicates that these nanoscale phase-separated glasses are quite distinct from the single phase nanoglasses (studied by Gleiter and others) in the following three respects: (i) they contain at least two structurally and compositionally distinct, nanodispersed, glassy phases, (ii) these phases are separated by comparatively sharp inter-phase boundaries, and (iii) thermally induced crystallization occurs via a complex, multi-step mechanism. Such materials, therefore, appear to constitute a new class of disordered systems that may be called a composite nanoglass. PMID- 26874494 TI - Thermal conductivity of Glycerol's liquid, glass, and crystal states, glass liquid-glass transition, and crystallization at high pressures. AB - To investigate the effects of local density fluctuations on phonon propagation in a hydrogen bonded structure, we studied the thermal conductivity kappa of the crystal, liquid, and glassy states of pure glycerol as a function of the temperature, T, and the pressure, p. We find that the following: (i) kappacrystal is 3.6-times the kappaliquid value at 140 K at 0.1 MPa and 2.2-times at 290 K, and it varies with T according to 138 * T(-0.95); (ii) the ratio kappaliquid (p)/kappaliquid (0.1 MPa) is 1.45 GPa(-1) at 280 K, which, unexpectedly, is about the same as kappacrystal (p)/kappacrystal (0.1 MPa) of 1.42 GPa(-1) at 298 K; (iii) kappaglass is relatively insensitive to T but sensitive to the applied p (1.38 GPa(-1) at 150 K); (iv) kappaglass-T plots show an enhanced, pressure dependent peak-like feature, which is due to the glass to liquid transition on heating; (v) continuous heating cold-crystallizes ultraviscous glycerol under pressure, at a higher T when p is high; and (vi) glycerol formed by cooling at a high p and then measured at a low p has a significantly higher kappa than the glass formed by cooling at a low p. On heating at a fixed low p, its kappa decreases before its glass-liquid transition range at that p is reached. We attribute this effect to thermally assisted loss of the configurational and vibrational instabilities of a glass formed at high p and recovered at low p, which is different from the usual glass-aging effect. While the heat capacity, entropy, and volume of glycerol crystal are less than those for its glass and liquid, kappacrystal of glycerol, like its elastic modulus and refractive index, is higher. We discuss these findings in terms of the role of fluctuations in local density and structure, and the relations between kappa and the thermodynamic quantities. PMID- 26874495 TI - CCSD(T)/CBS fragment-based calculations of lattice energy of molecular crystals. AB - A comparative study of the lattice energy calculations for a data set of 25 molecular crystals is performed using an additive scheme based on the individual energies of up to four-body interactions calculated using the coupled clusters with iterative treatment of single and double excitations and perturbative triples correction (CCSD(T)) with an estimated complete basis set (CBS) description. The CCSD(T)/CBS values on lattice energies are used to estimate sublimation enthalpies which are compared with critically assessed and thermodynamically consistent experimental values. The average absolute percentage deviation of calculated sublimation enthalpies from experimental values amounts to 13% (corresponding to 4.8 kJ mol(-1) on absolute scale) with unbiased distribution of positive to negative deviations. As pair interaction energies present a dominant contribution to the lattice energy and CCSD(T)/CBS calculations still remain computationally costly, benchmark calculations of pair interaction energies defined by crystal parameters involving 17 levels of theory, including recently developed methods with local and explicit treatment of electronic correlation, such as LCC and LCC-F12, are also presented. Locally and explicitly correlated methods are found to be computationally effective and reliable methods enabling the application of fragment-based methods for larger systems. PMID- 26874496 TI - Dynamical properties of water-methanol solutions. AB - We study the relaxation times talpha in the water-methanol system. We examine new data and data from the literature in the large temperature range 163 < T < 335 K obtained using different experimental techniques and focus on how talpha affects the hydrogen bond structure of the system and the hydrophobicity of the alcohol methyl group. We examine the relaxation times at a fixed temperature as a function of the water molar fraction XW and observe two opposite behaviors in their curvature when the system moves from high to low T regimes. This behavior differs from that of an ideal solution in that it has excess values located at different molar fractions (XW = 0.5 for high T and 0.75 in the deep supercooled regime). We analyze the data and find that above a crossover temperature T ~ 223 K, hydrophobicity plays a significant role and below it the water tetrahedral network dominates. This temperature is coincident with the fragile-to-strong dynamical crossover observed in confined water and supports the liquid-liquid phase transition hypothesis. At the same time, the reported data suggest that this crossover temperature (identified as the Widom line temperature) also depends on the alcohol concentration. PMID- 26874497 TI - Water adsorption on the LaMnO3 surface. AB - Studying the adsorption of water on the metallic LaMnO3 surface can provide insight into this complicated surface-adsorbate interaction. Using density functional theory, we investigated the adsorption of a water monomer, dimer, trimer, and a monolayer on the surface. The electronic structure of ground state configurations is explored using analysis of density of states, charge density, and crystal orbital overlap populations. We found that the interaction between the surface and water molecules is stronger than hydrogen bonding between molecules, which facilitates wetting of the surface. Adsorbed water molecules form very strong hydrogen bonds, with substantially shifted OH stretch modes. For the monolayer of adsorbed water, a hint of a bilayer is observed with a height separation of only 0.2 A. However, simulated scanning tunneling microscopy images and vibrational spectra suggest a significant difference between the two layers due to intermolecular bonding and interaction with the substrate. PMID- 26874498 TI - Entropic screening preserves non-equilibrium nature of nematic phase while enthalpic screening destroys it. AB - The present manuscript describes the role of entropic and enthalpic forces mediated by organic non-polar (hexane) and polar (methanol) solvents on the bulk and microscopic phase transition of a well known nematic liquid crystalline material MBBA (N-(4-methoxybenzylidene)-4-butylaniline) through Differential Scanning calorimetry (DSC), UV-Visible (UV-Vis), and Fourier Transform Infrared (FTIR) spectroscopy. DSC study indicates continuous linear decreases in both nematic-isotropic (N-I) phase transition temperature and enthalpy of MBBA in presence of hexane while both these parameters show a saturation after an initial decay in methanol. These distinct transitional behaviours were explained in terms of the "depletion force" model for entropic screening in hexane and "screening self-screening" model for methanol. Heating rate dependent DSC studies find that non-Arrhenius behaviour, characteristic of pristine MBBA and a manifestation of non-equilibrium nature [Dan et al., J. Chem. Phys. 143, 094501 (2015)], is preserved in presence of entropic screening in the hexane solution, while it changes to Arrhenius behaviour (signifying equilibrium behaviour) in presence of enthalpic screening in methanol solution. FTIR spectra show similar dependence on the solvent induced screening in the intensities of the imine (-C = N) stretch and the out-of-plane distortion vibrations of the benzene rings of MBBA with hexane and methanol as in DSC, further establishing our entropic and enthalpic screening models. UV-Vis spectra of the electronic transitions in MBBA as a function of temperature also exhibit different dependences of intensities on the solvent induced screening, and an exponential decrease is observed in presence of hexane while methanol completely changes the nature of interaction to follow a linear dependence. PMID- 26874499 TI - Surfactant-induced core/shell phase equilibrium in hydrogels. AB - The formation of core/shell structures in hydrogels upon interaction with surfactants is a well-known phenomenon, but whether they are equilibrium states or not is still under debate. This paper presents an equilibrium theory of phase coexistence in hydrogels meant to answer the question of the stability of core/shell separation. The theory suggests that core/shell separation caused by surfactants can indeed be thermodynamically stable if the amount of added surfactant is not too large, but that the exact phase behaviour is governed by both the volume and concentration of the added surfactant solution. PMID- 26874500 TI - Minimal physical requirements for crystal growth self-poisoning. AB - Self-poisoning is a kinetic trap that can impair or prevent crystal growth in a wide variety of physical settings. Here we use dynamic mean-field theory and computer simulation to argue that poisoning is ubiquitous because its emergence requires only the notion that a molecule can bind in two (or more) ways to a crystal; that those ways are not energetically equivalent; and that the associated binding events occur with sufficiently unequal probability. If these conditions are met then the steady-state growth rate is in general a non monotonic function of the thermodynamic driving force for crystal growth, which is the characteristic of poisoning. Our results also indicate that relatively small changes of system parameters could be used to induce recovery from poisoning. PMID- 26874501 TI - Glass-like dynamics of the strain-induced coil/helix transition on a permanent polymer network. AB - We study the stress response to a step strain of covalently bonded gelatin gels in the temperature range where triple helix reversible crosslink formation is prohibited. We observe slow stress relaxation towards a T-dependent finite asymptotic level. We show that this is assignable to the strain-induced coil -> helix transition, previously evidenced by Courty et al. [Proc. Natl. Acad. Sci. U. S. A. 102, 13457 (2005)], of a fraction of the polymer strands. Relaxation proceeds, in a first stage, according to a stretched exponential dynamics, then crosses over to a terminal simple exponential decay. The respective characteristic times tauK and tauf exhibit an Arrhenius-like T-dependence with an associated energy E incompatibly larger than the activation barrier height for the isomerisation process which sets the clock for an elementary coil -> helix transformation event. We tentatively assign this glass-like slowing down of the dynamics to the long-range couplings due to the mechanical noise generated by the local elementary events in this random elastic medium. PMID- 26874502 TI - Structural relaxation of acridine orange dimer in bulk water and inside a single live lung cell. AB - Structural relaxation of the acridine orange (AO) dimer in bulk water and inside a single live lung cell is studied using time resolved confocal microscopy and molecular dynamics (MD) simulations. The emission maxima (lambdaem (max)~ 630 nm) of AO in a lung cancer cell (A549) and a non-cancer lung fibroblast cell (WI38) suggest that AO exists as a dimer inside the cell. Time-dependent red shift in emission maximum indicates dynamic relaxation of the AO dimer (in the excited state) with a time constant of 500-600 ps, both in bulk water and inside the cell. We have calculated the equilibrium relaxation dynamics of the AO dimer in the ground state using MD simulations and found a slow component of time scale ~ 350 ps. The intra- and inter-molecular components of the total relaxation dynamics of the AO dimer reveal the presence of a slow component of the order of a few hundred picoseconds. Upon restricting intra-molecular dye dynamics by harmonic constraint between AO monomers, the slow component vanishes. Combining the experimental observations and MD simulation results, we ascribe the slow component of the dynamic relaxation of the AO dimer to the structural relaxation, namely, fluctuations in the distance between the two monomers and associated fluctuation in the number of water molecules. PMID- 26874503 TI - Grand-canonical simulation of DNA condensation with two salts, effect of divalent counterion size. AB - The problem of DNA- DNA interaction mediated by divalent counterions is studied using a generalized grand-canonical Monte-Carlo simulation for a system of two salts. The effect of the divalent counterion size on the condensation behavior of the DNA bundle is investigated. Experimentally, it is known that multivalent counterions have strong effect on the DNA condensation phenomenon. While tri- and tetra-valent counterions are shown to easily condense free DNA molecules in solution into toroidal bundles, the situation with divalent counterions is not as clear cut. Some divalent counterions like Mg(+2) are not able to condense free DNA molecules in solution, while some like Mn(+2) can condense them into disorder bundles. In restricted environment such as in two dimensional system or inside viral capsid, Mg(+2) can have strong effect and able to condense them, but the condensation varies qualitatively with different system, different coions. It has been suggested that divalent counterions can induce attraction between DNA molecules but the strength of the attraction is not strong enough to condense free DNA in solution. However, if the configuration entropy of DNA is restricted, these attractions are enough to cause appreciable effects. The variations among different divalent salts might be due to the hydration effect of the divalent counterions. In this paper, we try to understand this variation using a very simple parameter, the size of the divalent counterions. We investigate how divalent counterions with different sizes can lead to varying qualitative behavior of DNA condensation in restricted environments. Additionally, a grand canonical Monte-Carlo method for simulation of systems with two different salts is presented in detail. PMID- 26874504 TI - Erratum: "Tip-induced deformation of a phospholipid bilayer: Theoretical perspective of sum frequency generation imaging" [J. Chem. Phys. 141, 154201 (2014)]. PMID- 26874506 TI - PIPOM or the need of a new acronym. PMID- 26874505 TI - Does serotonin-modulating anticonsolidation protein (SMAP) influence the choice of turning direction in carps, Cyprinus carpio, in a T-maze? AB - Serotonin-modulating anticonsolidation protein (SMAP) can impair the formation of memory traces in mammals and fish. We have studied the influence of SMAP on behavioral lateralization of juvenile carps Cyprinus carpio in a T-maze without food reinforcement in three experimental groups (n = 8 each): (1) negative control (intact animals); (2) experimental group (fish injected ICV with SMAP; 2 MUl, 1.2 mg ml(-1)) and (3) active control group (fish injected ICV with inactivated SMAP). The behavioral lateralization of carps was observed on the 1st, 2nd, 3rd and 6th days after the injections. In each observation session, a fish was placed five times in a start chamber of the T-maze. The direction of the turn upon leaving the start chamber, as well as the latency from the opening of start chamber flap to the fish's turn was registered. The number of right turns (of all five turns observed during the session) was a criterion of lateralization. It was found that carps have no inherent preference for turning left or right. The SMAP injection did not influence the choice of turning direction, but increases latency values insignificantly. The results are important for the correct interpretation and clarification of data reporting the role of SMAP in training and formation of spatial memory of fish in a maze. PMID- 26874507 TI - Perioperative outcomes and costs of laparoscopic versus open inguinal hernia repair. AB - PURPOSE: Studies comparing laparoscopic (LIHR) vs. open inguinal hernia repair (OIHR) have shown similar recurrence rates but have disagreed on perioperative outcomes and costs. The aim of this study is to compare laparoscopic vs. open outcomes and costs. METHODS: The National Surgical Quality Improvement Program (NSQIP) was used to compare durations of surgery, anesthesia time, and length of stay (LOS). The University HealthSystem Consortium (UHC) was used to review the cost and complications between approaches. Patients were matched on demographics, year of procedure and surgical approach between datasets for statistical analysis. RESULTS: A sample of 5468 patients undergoing OIHR (N = 4,693) or LIHR (N = 775) was selected from UHC from 2008-2011. An identical number of patients from NSQIP were matched to those from UHC resulting in a total of 10,936 records. LIHR patients had shorter duration of wait from admission to operation (p < 0.05). Conversely, LIHR patients had longer operating time (p < 0.05), duration of anesthesia (p < 0.05), and time in the operating room (p < 0.05).Overall complication rate was higher in open (3.1 vs. 1.8 %, p < 0.05). Cost favored open over LIHR ($4360 vs $5105). The cost discrepancy mainly stemmed from LIHR supplies ($1448 vs. $340; p < 0.05) and OR services ($1380 vs. $1080; p < 0.05). CONCLUSION: This study demonstrates the LOS and perioperative outcomes were superior in the LIHR group; however, the overall cost was higher due to the supplies. Advancement in technology, surgeons' skill level and preference of supplies are all factors in decreasing the overall cost of LIHR. PMID- 26874508 TI - Mediators of repeat mammography in two tailored interventions for Iranian women. AB - BACKGROUND: Many theory-based interventions exist that incorporate theoretical constructs (e.g., self-efficacy, behavioral control) believed to increase the likelihood of mammography. Nonetheless, little work to date has examined if increased screening among women receiving such interventions occurs due to changes in these targeted constructs. The aim of this study is to address this gap in the literature in the context of two interventions for improving regular screening among Iranian women. METHODS: A sample of 176 women over 50 years old in Tehran, Iran were randomly allocated into one of these three conditions: 1) an intervention based on Health Belief Model (HBM); 2) an intervention based on an integration of the HBM and selected constructs from the TPB (TPB); and 3) a control group (CON). Questionnaires were administered before the intervention and after a 6-month follow-up. The Preacher and Hayes method of mediation was used in analytic models. RESULTS: Changes in susceptibility, self-efficacy, and perceived control appeared to mediate HBM-CON differences in screening. Barriers attenuated the mediating effect of self-efficacy. Changes in barriers and self-efficacy appeared to mediate TPB-CON differences in screening. CONCLUSION: This study was successful in identifying which theory-based constructs appear to underlie the effectiveness of HBM- and TPB-based interventions. Specific constructs have been identified that should be targeted in clinical practice to increase mammography practices among Iranian women. PMID- 26874509 TI - Carnitine palmitoyl transferase 2 polymorphism may be associated with enterovirus 71 severe infection in a Chinese population. AB - Genetic polymorphism in the carnitine palmitoyl transferase 2 (CPT2) gene has been reported to be a susceptibility factor in a number of syndromes of acute encephalopathy with various infectious diseases, but evidence of its effect on enterovirus 71 (EV71) infection is lacking. The goal of this study was to examine the relationship between genetic polymorphism of CPT2 and severity of EV71 infection in a Chinese population. PCR of five exons of the CPT2 gene was carried out to identify single-nucleotide polymorphisms (SNPs) in EV71-infected subjects (n = 333), including mild cases (n = 271) and severe cases (n = 62) as well as healthy controls (n = 328). Blood ATP levels were measured within 24 h of admission. The frequency of the A allele of rs1799821 (P = 0.023) and the G allele of rs2229291 (P = 0.009) in the CPT2 gene was higher in patients with severe EV71 infection. The A-G haplotype of rs1799821and rs2229291 was directly linked to EV71 severe infection risk when compared to all other haplotypes (OR = 2.005, 95 % CI = 1.087-3.700, P = 0.024). The blood ATP levels of severe cases were significantly lower than in mild cases (P < 0.01) and controls (P < 0.01). A significant negative correlation was observed in haplotype A-G between ATP levels and physical findings in severe cases (P < 0.05). These findings suggest that CPT2 polymorphism may be associated with severity of EV71 infection and that the A-G haplotype of the CPT2 gene is involved in the inflammatory process of EV71 infection. PMID- 26874510 TI - Detection and genome sequence of a new betapartitivirus associated with Cucurbitaria piceae Borthw. fungus causing bud blight of spruce in the Czech Republic. AB - A new bisegmented dsRNA virus has been detected in shoots of blue spruce with bud blight disease symptoms and infection by Cucurbitaria piceae (Bortw.) fungus. The virus genome consists of two segments that are 2071 and 2257 nt long, encoding the putative RNA polymerase and capsid protein, respectively. Rosellinia necatrix partitivirus 1 is a closely related virus with 45 % amino acid sequence identity in the polymerase, and crimson clover cryptic virus 2 has 36 % amino acid sequence identity in the capsid protein. Based on taxonomic criteria, the virus should be classified as a member of the genus Betapartitivirus (family Partitiviridae). The name Cucurbitaria piceae partitivirus 1 and acronym CpPV1 are proposed. PMID- 26874511 TI - Effect of low-dose valsartan on proteinuria in normotensive immunoglobulin A nephropathy with minimal proteinuria: a randomized trial. AB - BACKGROUND/AIMS: Immunoglobulin A nephropathy (IgAN) is a generally progressive disease, even in patients with favorable prognostic features. In this study, we aimed to investigate the antiproteinuric effect and tolerability of low-dose valsartan (an angiotensin II receptor blocker) therapy in normotensive IgAN patients with minimal proteinuria of less than 0.5 to 1.0 g/day. METHODS: Normotensive IgAN patients, who had persistent proteinuria with a spot urine protein-to-creatinine ratio of 0.3 to 1.0 mg/mg creatinine, were recruited from five hospitals and randomly assigned to either 40 mg of valsartan as the low-dose group or 80 mg of valsartan as the regular-dose group. Clinical and laboratory data were collected at baseline, and at 4, 8, 12, and 24 weeks after valsartan therapy. RESULTS: Forty-three patients (low-dose group, n = 23; regular-dose group, n = 20) were enrolled in the study. Proteinuria decreased significantly not only in the regular-dose group but also in the low-dose group. The change in urine protein-to-creatinine ratio at week 24 was -41.3% +/- 26.1% (p < 0.001) in the regular-dose group and -21.1% +/- 45.1% (p = 0.005) in the low-dose group. In the low-dose group, blood pressure was constant throughout the study period, and there was no symptomatic hypotension. In the regular-dose group, blood pressure decreased at weeks 8 and 12. No significant change in glomerular filtration rate, serum creatinine level, or serum potassium level was observed during the study period. CONCLUSIONS: Our results suggest that low-dose valsartan can significantly reduce proteinuria without causing any intolerability in normotensive IgAN patients with minimal proteinuria. PMID- 26874512 TI - Combination transarterial chemoembolization and radiofrequency ablation therapy for early hepatocellular carcinoma. AB - BACKGROUND/AIMS: We compared the recurrence of hepatocellular carcinoma (HCC) and the survival of patients who received radiofrequency ablation (RFA) after transarterial chemoembolization (TACE) with patients treated with TACE or RFA alone. METHODS: This study included 201 patients with HCC, who were consecutively enrolled at Seoul St. Mary's Hospital between December 2004 and February 2010. Inclusion criteria were a single HCC <= 5.0 cm or up to three HCCs <= 3.0 cm. We used a propensity score model to compare HCC patients (n = 87) who received RFA after TACE (TACE + RFA) with those who received TACE (n = 71) or RFA alone (n = 43). RESULTS: The median follow-up period was 33.3 months (range, 6.8 to 80.9). The TACE + RFA group showed significantly lower local recurrence than the RFA or TACE groups (hazard ratio [HR], 0.309; 95% confidence interval [CI], 0.130 to 0.736; p = 0.008; and HR, 0.352; 95% CI, 0.158 to 0.787; p = 0.011, respectively). The overall survival was significantly better in the TACE + RFA group compared to the RFA group (HR, 0.422; 95% CI, 0.185 to 0.964; p = 0.041). However, the survival benefit was not different between the TACE + RFA and TACE groups (p = 0.124). Subgroup analysis showed that among patients with a tumor size < 3 cm, the TACE + RFA group had significantly better long-term survival than those in the TACE or RFA groups (p = 0.017, p = 0.004, respectively). CONCLUSIONS: TACE + RFA combination treatment showed favorable local recurrence and better overall survival rates in early-stage HCC patients. Patients with tumors < 3 cm are likely to benefit more from TACE + RFA combination treatment. Additional studies are needed for the selection of suitable HCC patients for TACE + RFA treatment. PMID- 26874513 TI - Controlling endemic multidrug-resistant Acinetobacter baumannii in Intensive Care Units using antimicrobial stewardship and infection control. AB - BACKGROUND/AIMS: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital onset MDR A. baumannii among patients in the ICUs. RESULTS: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 +/- 82.26 defined daily doses per 1,000 patient-days to 94.85 +/- 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year. PMID- 26874515 TI - Mixed-phenotype acute leukemia treated with decitabine. PMID- 26874514 TI - Use of deferasirox, an iron chelator, to overcome imatinib resistance of chronic myeloid leukemia cells. AB - BACKGROUND/AIMS: The treatment of chronic myeloid leukemia (CML) has achieved impressive success since the development of the Bcr-Abl tyrosine kinase inhibitor, imatinib mesylate. Nevertheless, resistance to imatinib has been observed, and a substantial number of patients need alternative treatment strategies. METHODS: We have evaluated the effects of deferasirox, an orally active iron chelator, and imatinib on K562 and KU812 human CML cell lines. Imatinib-resistant CML cell lines were created by exposing cells to gradually increasing concentrations of imatinib. RESULTS: Co-treatment of cells with deferasirox and imatinib induced a synergistic dose-dependent inhibition of proliferation of both CML cell lines. Cell cycle analysis showed an accumulation of cells in the subG1 phase. Western blot analysis of apoptotic proteins showed that co-treatment with deferasirox and imatinib induced an increased expression of apoptotic proteins. These tendencies were clearly identified in imatinib resistant CML cell lines. The results also showed that co-treatment with deferasirox and imatinib reduced the expression of BcrAbl, phosphorylated Bcr Abl, nuclear factor-kappaB (NF-kappaB) and beta-catenin. CONCLUSIONS: We observed synergistic effects of deferasirox and imatinib on both imatinib-resistant and imatinib-sensitive cell lines. These effects were due to induction of apoptosis and cell cycle arrest by down-regulated expression of NF-kappaB and beta-catenin levels. Based on these results, we suggest that a combination treatment of deferasirox and imatinib could be considered as an alternative treatment option for imatinib-resistant CML. PMID- 26874517 TI - Measurement of gastrocnemius muscle elasticity by shear wave elastography: association with passive ankle joint stiffness and sex differences. AB - PURPOSE: Passive joint stiffness is an important quantitative measure of flexibility, but is affected by muscle volume and all of the anatomical structures located within and over the joint. Shear wave elastography can assess muscle elasticity independent of the influences of muscle volume and the other nearby anatomical structures. We determined how muscle elasticity, as measured using shear wave elastography, is associated with passive joint stiffness and patient sex. METHODS: Twenty-six healthy men (24.4 +/- 5.9 years) and 26 healthy women (25.2 +/- 4.8 years) participated in this study. The passive ankle joint stiffness and tissue elasticity of the medial gastrocnemius (MG) were quantified with the ankle in 30 degrees plantar flexion (PF), a neutral anatomical position (NE), and 20 degrees dorsiflexion (DF). RESULTS: No significant difference in passive joint stiffness by sex was observed with the ankle in PF, but significantly greater passive ankle joint stiffness in men than in women was observed in NE and DF. The MG elasticity was not significantly associated with joint stiffness in PF or NE, but it was significantly associated with joint stiffness in DF. There were no significant differences in MG elasticity by sex at any ankle position. CONCLUSIONS: Muscle elasticity, measured independent of the confounding effects of muscle volume and the other nearby anatomical structures, is associated with passive joint stiffness in the joint position where the muscle is sufficiently lengthened, but does not vary by sex in any joint position tested. PMID- 26874518 TI - New future of cell biology and toxicology: thinking deeper. PMID- 26874516 TI - Identification of Relationships Between Interleukin 15 mRNA and Brain-Derived Neurotrophic Factor II mRNA Levels With Formal Components of Temperament in Asthmatic Patients. AB - Asthma is a chronic inflammatory and heterogeneous disease developing mostly through allergic inflammation, which modifies the expression of various cytokines and neurotrophins. Previous studies suggest the involvement of interleukin (IL) 15 in the regulation of immune response in asthma. Brain-derived neurotrophic factor (BDNF) II plays an important role as a regulator of development and survival of neurons as well as maintenance of their physiological activity. Chronic stress associated with asthma and elevated IL-15 mRNA and BDNFII mRNA levels may affect the mood and a subjective sensation of dyspnoea-inducing anxiety. Psychopathological variables and numerous cytokine/neurotrophin interactions influence the formation of temperament and strategies of coping with stress. The aim of the study was to identify the role of IL-15 mRNA and BDNFII mRNA expressions and their effect on components of temperament and strategies of coping with stress in asthmatics. A total of 352 subjects (176 healthy volunteers and 176 asthmatic patients) participated in the study. The Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale were applied in all the subjects. The expression of IL-15 and BDNFII gene was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Different levels of IL-15 and BDNFII expressions between healthy volunteers and patients were revealed in the study. IL-15 enhanced the BDNFII mRNA expression among patients with bronchial asthma. The depression level negatively correlated with the BDNFII mRNA expression. This neurotrophin modified the temperament variable. BDNFII significantly affected (proportional relationship) the level of briskness in asthmatic patients. BDNFII might influence the level and style of coping with stress (emotion-oriented style). This hypothesis requires further studies on protein functional models. The obtained data confirms the role of IL-15 and BDNFII in the pathomechanisms of depression and formation of selected traits defining the temperament in asthmatics. PMID- 26874520 TI - Single-strand gap repair involves both RecF and RecBCD pathways. AB - Homologous recombination repairs discontinuities in DNA including single-strand gaps (SSGs) and double-strand breaks (DSBs). This commentary describes how the RecBCD and RecF pathways might be exchangeable for the repair of their respective DSB and SSG canonical substrates. In particular, I will discuss how the RecBCD pathway could engage in the repair of an SSG even when the latter is not associated with a DSB. PMID- 26874521 TI - Adapting to Florida's riverine woodlands: the population status and feeding ecology of the Silver River rhesus macaques and their interface with humans. AB - The study of primates living in novel environments represents an interesting context in which to examine patterns of behavioral and ecological flexibility. Our research focused on an understudied, anthropogenically introduced primate population living in Florida, USA: the Silver River rhesus macaques (Macaca mulatta). To better understand how this population has adapted to life in Florida's riparian woodlands, we collected data on the diet and size of the rhesus macaque population and its encounters with boaters along the Silver River from January to May 2013. Using scan sampling and all-occurrences sampling, we collected 166 h of diet data and 105 h of human-macaque encounter data, respectively. We confirmed previous reports that four social groups comprise the Silver River macaque population, totaling 118 individuals. The Silver River macaques predominantly consumed leaves and other vegetative plant parts (87.5 %), with ash trees serving as a staple food (66.5 % of feeding records). Although human-macaque encounters were frequent (80 % of 611 boats observed), only a small proportion of boats (11.5 %) provisioned the macaques. Motorized boats (e.g., pontoon and motor boats) were more likely to provision, while kayaks and canoes were more likely to move in close proximity of the macaques situated at the river's edge. Our results indicate that the Silver River macaques have adjusted to life in the New World by adopting a temperate-dwelling feeding strategy and by incorporating locally available foods (e.g., sedges) into their diet. They have also learned that the river's edge provides opportunities to receive provisions from boaters. However, because the rate of provisioning is low, these foods likely play a filler fallback role. Given that provisioning and direct contact between macaques and boaters are infrequent but proximity to the macaques is a concern, our findings have important implications for the management of the human macaque interface along the Silver River and beyond. PMID- 26874519 TI - Contemporary mechanical circulatory support therapy for postcardiotomy shock. AB - Significant progress has been made in the use of mechanical circulatory support (MCS), particularly in the clinical success in durable left ventricular assist device. Short-term MCS has also advanced in the form of venoarterial extracorporeal membrane oxygenation, external centrifugal VADs as well as percutaneous VADs. Postcardiotomy shock (PCS) is a rare clinical entity associated with substantial morbidity and mortality. It is characterized by heart failure that either results in an inability to wean from cardiopulmonary bypass or that occurs in the immediate postoperative period, accounting for the most common indication for MCS. The reported in-hospital mortality of the PCS patients remains high, consistently over 50%, despite ongoing refinements of MCS technology. The optimization of selection criteria and the prompt institution of MCS are likely the keys to improving this persistently high mortality rate. Unfortunately, the lack of a clear definition for PCS in the literature limits scientific analyses and comparison of the existing evidence. To establish the treatment strategy and appropriately manage this challenging disease, substantial and fundamental effort by the cardiovascular society is imperative. PMID- 26874522 TI - RBP-J is required for M2 macrophage polarization in response to chitin and mediates expression of a subset of M2 genes. AB - Development of alternatively activated (M2) macrophage phenotypes is a complex process that is coordinately regulated by a plethora of pathways and factors. Here, we report that RBP-J, a DNA-binding protein that integrates signals from multiple pathways including the Notch pathway, is critically involved in polarization of M2 macrophages. Mice deficient in RBP-J in the myeloid compartment exhibited impaired M2 phenotypes in vivo in a chitin-induced model of M2 polarization. Consistent with the in vivo findings, M2 polarization was partially compromised in vitro in Rbpj-deficient macrophages as demonstrated by reduced expression of a subset of M2 effector molecules including arginase 1. Functionally, myeloid Rbpj deficiency impaired M2 effector functions including recruitment of eosinophils and suppression of T cell proliferation. Collectively, we have identified RBP-J as an essential regulator of differentiation and function of alternatively activated macrophages. PMID- 26874523 TI - Modeling xeroderma pigmentosum associated neurological pathologies with patients derived iPSCs. AB - Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients. PMID- 26874524 TI - Perineal body stretch during labor does not predict perineal laceration, postpartum incontinence, or postpartum sexual function: a cohort study. AB - INTRODUCTION AND HYPOTHESIS: The perineum stretches naturally during obstetrical labor, but it is unknown whether this stretch has a negative impact on pelvic floor outcomes after a vaginal birth (VB). We aimed to evaluate whether perineal stretch was associated with postpartum pelvic floor dysfunction, and we hypothesized that greater perineal stretch would correlate with worsened outcomes. METHODS: This was a prospective cohort study of primiparous women who had a VB. Perineal body (PB) length was measured antepartum, during labor, and 6 months postpartum. We determined the maximum PB (PBmax) measurements during the second stage of labor and PB change (DeltaPB) between time points. Women completed functional questionnaires and had a Pelvic Organ Prolapse Quantification (POP-Q) system exam 6 months postpartum. We analyzed the relationship of PB measurements to perineal lacerations and postpartum outcomes, including urinary, anal, and fecal incontinence, sexual activity and function, and POP-Q measurements. RESULTS: Four hundred and forty-eight women with VB and a mean age of 24 +/- 5.0 years with rare (5 %) third- or fourth-degree lacerations were assessed. During the second stage of labor, 270/448 (60 %) had perineal measurements. Mean antepartum PB length was 3.7 +/- 0.8 cm, with a maximum mean PB length (PBmax) during the second stage of 6.1 +/- 1.5 cm, an increase of 65 %. The change in PB length (DeltaPB) from antepartum to 6 months postpartum was a net decrease (-0.39 +/- 1.02 cm). PB change and PBmax were not associated with perineal lacerations or outcomes postpartum (all p > 0.05). CONCLUSIONS: PB stretch during labor is unrelated to perineal laceration, postpartum incontinence, sexual activity, or sexual function. PMID- 26874525 TI - Pelvic organ prolapse repair using the UpholdTM Vaginal Support System: a 1-year multicenter study. AB - INTRODUCTION AND HYPOTHESIS: The objective was to assess safety and clinical outcomes in women operated on using the UpholdTM Lite Vaginal Support System. METHODS: We carried out a 1-year, multicenter, prospective, single cohort study of 207 women with symptomatic Pelvic Organ Prolapse Quantification (POP-Q) stage >=2 apical pelvic organ prolapse, with or without concomitant anterior vaginal wall prolapse. Safety data were collected using a standardized questionnaire. Anatomical outcome was assessed by the POP-Q and subjective outcomes by the Pelvic Floor Distress Inventory after 2 months and 1 year using a one-way repeated measures analysis of variance. Pain was evaluated using a visual analog scale. RESULTS: The overall rate of serious complications was 4.3 % (9 out of 207 patients), including 3 patients with bladder perforations, 1 with bleeding >1,000 ml, 2 who had undergone re-operations with complete mesh removal because of pain, and 3 surgical interventions during follow-up because of mesh exposure. POP-Q stage <=1 after 1 year was 94 % and subjective symptom relief was reported by 91 % of patients (p < 0.001). Pain after 2 months and 1 year was 60 % lower compared with the preoperative mean (p < 0.001). Minor complications occurred in 20 women (9.7 %) and were dominated by lower urinary tract dysfunction. No predisposing risk factors for complications were found. CONCLUSIONS: The UpholdTM Lite procedure in women with apical pelvic organ prolapse provided satisfactory restoration of vaginal topography and symptom relief. However, serious complication rates were largely comparable with those of other transvaginal mesh kits. PMID- 26874527 TI - Editor's Introduction to the Special Section "Re-centering and Re-entering: Positioning Islam in the Bioethical Discourse". PMID- 26874526 TI - Locating the Social Origins of Mental Illness: The Explanatory Models of Mental Illness Among Clergy from Different Ethnic and Faith Backgrounds. AB - Clergy have historically provided 'healing' through various spiritual and medical modalities and even in modern, developed welfare economies they may still be an important help-seeking resource. Partnerships between religion and psychiatry are regularly advocated, but there is scant research on clergy explanatory models of illness. This paper aimed to explore their relationship with psychiatry and to examine how clergy in various faith groups conceptualised mental health problems. In this qualitative study using in-depth interviews, these issues were explored with 32 practising clergy in the UK from a range of different Christian, Muslim and Jewish faith organisations and ethnic backgrounds. This paper presents findings related to clergy explanatory models of mental illness and, in particular, how the social factors involved in causation are tinged with spiritual influences and implications, and how the meanings of mental distress assume a social and moral significance in distinctive localised matters. PMID- 26874528 TI - Differential modulation of cytosolic lipases activities in liver and adipose tissue by high-carbohydrate diets. AB - Several studies have demonstrated that a high-fructose (FRUC) diet induces metabolic and haemodynamic abnormalities, known as the metabolic syndrome, which are characterised by obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. In this study, the effect of a FRUC diet (60 % fructose) for 8 weeks on the metabolism of lipids in liver and epididymal adipose tissue from Wistar rats was compared with the AIN-93M diet and the effects of the AIN-93M diet were compared with a chow diet. The FRUC diet induced marked increases in both hepatocyte lipid droplet volume and postprandial serum levels of triacylglycerol (TAG), but reduced the postprandial serum levels of insulin. The AIN-93M diet induced marked increases in the hepatocyte lipid droplet volume and the serum levels of insulin, without affecting the serum levels of TAG. We found that isocaloric substitution of cornstarch, dextrinised cornstarch and sucrose (AIN-93M diet) for fructose did not affect the hepatic VLDL-TAG secretion and adipose tissue glucose uptake, lipolysis and cytosolic lipases activities in rats. However, the high-fructose diet induced a severe steatosis in liver accompanied by a decrease in cytosolic lipases activities. In adipose tissue, the FRUC diet induced a decrease in the lipoprotein lipase activity, and an increase in lipogenesis. FRUC and AIN-93M diets induced changes in lipid homeostasis in liver and adipose tissue by distinct biochemical mechanisms. PMID- 26874529 TI - Underactive Bladder. AB - Underactive bladder (UAB) is a very common condition leading to disabling lower urinary tract symptoms. There has been an increasing interest in this condition as there is no effective treatment currently available. UAB has been described in many ways, but there is no agreed upon consensus on its terminology. The prevalence of UAB may be underestimated. This review focuses on the terminology, pathophysiology, common causes, its treatment, and future areas of research. PMID- 26874530 TI - Prostate Cancer Imaging with Novel PET Tracers. AB - Molecular imaging of prostate cancer is in a dynamic phase of development. Currently approved techniques are limited and researchers have been working on novel agents to improve accuracy in targeting and detecting prostate tumors. In addition, the complexity of various prostate cancer states also contributes to the challenges in evaluating suitable radiotracer candidates. We have highlighted nuclear medicine tracers that focus on mechanisms involved in bone metastasis, prostate cancer cell membrane synthesis, amino acid analogs, androgen analogs, and the prostate specific membrane antigen. Encouraging results with many of these innovative radiotracer compounds will not only advance diagnostic capabilities for prostate cancer but open opportunities for theranostic applications to treat this worldwide malignancy. PMID- 26874531 TI - Novel Technologies in Urologic Surgery: a Rapidly Changing Scenario. AB - The introduction of laparoscopy and robotic surgery revolutionized the surgical management of urologic patients. Nonetheless, we live in an era of rapid changes, and we are probably still in the infancy of technology applied to surgery. When considering currently available technologies, there are several unmet needs to be addressed. These include the application of augmented reality, haptic feedback, tissue recognition, distant remote control, miniaturization of surgical instruments, the learning curve typical of the introduction of novel techniques, and excessive costs. In the next few years, evolution in imaging modalities in pre- and intraoperative surgical planning, as well as the introduction of novel minimally invasive platforms, would in part address these issues, substantially improving surgical outcomes. In addition, validated training programs would allow for the safe implementation of novel techniques in the clinical practice. Finally, a reduction in costs would be necessary to make technology affordable and to optimize healthcare resources. PMID- 26874533 TI - A Review Comparing Experience and Results with Bipolar Versus Monopolar Resection for Treatment of Bladder Tumors. AB - The standard treatment of non-muscle invasive bladder cancer (NMIBC) is transurethral resection (TUR) commonly using a monopolar electrocautery system. This system requires high energy and voltage to allow an electric current to run from the loop to the patient's skin. The heat generated leads to desiccation of small cells and difficulty to perform adequate histological analysis for severely cauterized pieces of tissues. On contrary, the electric current in bipolar systems does not traverse the patient and hence lower energy and voltage are used and minimal tissue damage is anticipated. In addition, the use of saline as an irrigant fluid eliminates the potential TUR syndrome from excess hypotonic fluid reabsorption. Furthermore, the lower energy dissipates as heat in tissues contributing to adequate hemostasis. This review presents the most recent studies and evidence on the differences between monopolar and bipolar systems for TUR of NMIBC as regards the perioperative and long-term outcomes. PMID- 26874532 TI - Pelvic Prolapse Repair in the Era of Mesh. AB - Pelvic organ prolapse repair with mesh remains the gold standard for advanced prolapse. There are several surgical approaches available to the pelvic reconstructive surgeon. Prolapse repair can be performed vaginally or abdominally using native tissue or may be augmented with a biologic or mesh patch. In this article, we will review the different approaches to prolapse repair, the role of mesh, and the risks and benefits of each option. Patient selection, surgical technique, and the rationale for using mesh will be explored. Complications from prolapse repair with mesh including dyspareunia, pelvic pain, mesh exposure, and reoperation will be discussed. PMID- 26874534 TI - Rectourethral Fistula Management. AB - Rectourethral fistula (RUF) is a rare condition that occurs, in most cases, as a consequence of prostate cancer treatments. Clinical suspicion and proper assessment prior to surgery are essential to adapt and successfully carry out an appropriate treatment plan. There are no randomized trials to guide clinical practice, and therefore, scientific evidence in this respect is limited. Expert recommendations seem to agree on the transperineal approach with flap interposition as the surgical treatment of choice in cases of complex fistulas, especially in those that have undergone prior radiation. Undoubtedly, the key to the successful treatment of the disease is the multidisciplinary and standardized management by physicians with experience in the field. PMID- 26874535 TI - Contemporary Status of Percutaneous Ablation for the Small Renal Mass. AB - Renal cell carcinoma is the tenth most common malignancy in the USA, with upwards of 61,000 new cases and resulting in more than 14,000 deaths annually. Although partial nephrectomy remains the standard treatment, image-guided nephron-sparing ablative techniques including cryoablation, radiofrequency ablation, and microwave ablation have emerged as treatment options in certain patient populations. Ablative therapies have high technical successes, low tumor recurrence rates, and preserve renal parenchymal volume. The purpose of this article is to provide an update on ablation therapies for small renal masses. PMID- 26874537 TI - Grading of Prostate Cancer: Past, Present, and Future. AB - The grading of prostate cancer has undergone significant changes since the adoption of the Gleason grading system in the 1970s. Gleason patterns 1 and 2 are no longer in use and the current Gleason score 6 of 10 is the lowest grade possible. Several specific morphologies that were historically considered Gleason grade 3 are currently assigned a Gleason pattern 4. Consequently, current Gleason score 6 cancers have a better prognosis than historic ones. There is now ample literature that supports that Gleason score 7 includes patients with very different prognosis; those with Gleason score 3 + 4 have a much better prognosis than patients with Gleason score 4 + 3. Within patients with high-grade cancer, it is now also clear that patients with Gleason score 8 have a significantly better prognosis than men with Gleason scores 9-10. Additionally, more recent studies have demonstrated that there is no significant difference in the prognosis of patients with Gleason score 9 or 10, making the distinction between the two pointless. A new contemporary grading system has been proposed that addresses these changes/problems and provides a simpler system with only five grades that reflect more accurately the prognosis of each group. We review the different changes applied to the Gleason scoring system since its conception as well as the studies leading to a new contemporary grading system. PMID- 26874536 TI - Evolving Guidance on Ureteric Calculi Management in the Acute Setting. AB - Ureteric colic is a common presentation to acute emergency services. The gold standard test for the diagnosis of acute ureteric colic is a non-contrast computer tomography of the kidneys ureters and bladder (CT KUB). Non-steroidal anti-inflammatory drugs (NSAIDs) should be used as first-line analgesia, with studies showing that there is no role for steroid or phosphodiesterase-5 inhibitors. There is emerging evidence that a high body mass index (BMI) is a risk factor. The drugs used to facilitate stone passage are known as medical expulsive therapy (MET). The most evaluated being alpha-blockers. The Spontaneous Urinary Stone Passage Enabled by Drugs (SUSPEND) trial was designed to evaluate the use of MET (tamsulosin and nifedipine). This trial showed that there was no difference with MET and placebo for the spontaneous passage of ureteric stones. There is an emerging role for the use of primary ureteroscopy in the management of non-infective ureteric stones. PMID- 26874539 TI - This diagnosis is nothing to sneeze at! PMID- 26874540 TI - Emergency Nurses' Perspectives: Factors Affecting Caring. AB - Caring is a universal phenomenon. However, as a result of higher patient acuity and staff shortages within the chaotic ED environment, caring behaviors may be in peril. The purpose of this study was to gain insight into the meaning of caring from the perspective of emergency nurses. Exploring nurses' perspectives of caring is central to improving staffing and retention issues in this unique work environment. METHODS: As part of a larger study, a subsample of emergency nurses who work in public hospitals in Manitoba, Canada (n = 17) were interviewed. A qualitative descriptive design was used to gain insight into the caring perspectives of nurses by asking them, "What does caring meaning to you?" and "What affects caring in your practice in the emergency department?" Emerging themes were extracted through analysis of audio tapes and transcripts. RESULTS: Advocacy and holistic care emerged as major themes in the meaning of caring for emergency nurses. Caring was affected by a number of factors, including workload, lack of time, staffing issues, shift work, and lack of self-care. However, lack of management support was the most consistent hindrance to caring identified by study participants. DISCUSSION: Caring continues to be a unifying concept in nursing; however, influencing factors continue to undermine caring for emergency nurses. Caring is not subsidiary to nursing; it is the central core of nursing. Therefore, fostering a caring working environment is essential for nurses to practice holistic nursing care. It is also imperative to job satisfaction and the retention of emergency nurses. PMID- 26874538 TI - A review on factors affecting microcystins production by algae in aquatic environments. AB - Microcystins, a toxin produced by Microcystis aeruginosa have become a global environmental issue in recent years. As a consequence of eutrophication, microcystins have become widely disseminated in drinking water sources, seriously impairing drinking water quality. This review focuses on the relationship between microcystins synthesis and physical, chemical, and biological environmental factors that are significant in controlling their production. Light intensity and temperature are the more important physical factors, and in many cases, an optimum level for these two factors has been observed. Nitrogen and phosphorus are the key chemical factors causing frequent occurrence of harmful algal blooms and microcystins production. The absorption of nutrients and metabolic activities of algae are affected by different concentrations and forms of nitrogen and phosphorus, leading to variations in microcystins production Metal ions and emerging pollutants are other significant chemical factors, whose comprehensive impact is still being studied. Algae can also interact with biological agents like predators and competitors in aquatic environments, and such interactions are suggested to promote MCs production and release. This review further highlights areas that require further research in order to gain a better understanding of microcystins production. It provides a theoretical basis for the control of microcystins production and releasing into aquatic environments. PMID- 26874541 TI - Unfamiliar Devices and Handoff Assumptions Can Lead to Safety Consequences. PMID- 26874543 TI - Radiation dose distribution in functional heart regions from tangential breast cancer radiotherapy. AB - BACKGROUND AND PURPOSE: To analyze the distribution of individually-determined radiation dose to the heart and its functional sub-structures after radiotherapy in breast cancer patients treated in Germany during 1998-2008. MATERIAL AND METHODS: We obtained electronic treatment planning records for 769 female breast cancer patients treated with megavoltage tangential field radiotherapy. All dose distributions were re-calculated using Eclipse with the anisotropic analytical algorithm (AAA) for photon fields, and the electron Monte Carlo algorithm for electron boost fields. Based on individual dose volume histograms for the complete heart and several functional sub-structures, we estimated various dose measures in patient groups. RESULTS: Mean heart dose spanned a range of 0.9 19.1Gy for left-sided radiotherapy and 0.3-11.6Gy for right-sided radiotherapy. Average (median) mean heart dose was 4.6Gy (3.7Gy) for left-sided radiotherapy, and 1.7Gy (1.4Gy) for right-sided RT. With left-sided radiotherapy, 66% of the patients had 2cm(3) of the complete heart exposed to at least 40Gy. Younger age, higher body mass index, tumor location in a medial quadrant, and presence of a parasternal field were also associated with higher heart dose. CONCLUSION: Tumor location and treatment choices influence cardiac dose with complex interactions. There is considerable variability in heart dose, with dose metrics of different cardiac sub-structures showing different patterns in their dependency on external influences. Dose-response analysis of late cardiac effects after radiotherapy requires detailed individual dosimetry. PMID- 26874544 TI - Inactivated polio vaccine introduction in south Asia--1 year on. PMID- 26874542 TI - Myeloid-derived suppressor cells reveal radioprotective properties through arginase-induced l-arginine depletion. AB - BACKGROUND AND PURPOSE: High arginase-1 (Arg) expression by myeloid-derived suppressor cells (MDSC) is known to inhibit antitumor T-cell responses through depletion of l-arginine. We have previously shown that nitric oxide (NO), an immune mediator produced from l-arginine, is a potent radiosensitizer of hypoxic tumor cells. This study therefore examines whether Arg(+) overexpressing MDSC may confer radioresistance through depleting the substrate for NO synthesis. MATERIAL AND METHODS: MDSC and Arg expression were studied in preclinical mouse CT26 and 4T1 tumor models and further validated in rectal cancer patients in comparison with healthy donors. The radioprotective effect of MDSC was analyzed in hypoxic tumor cells with regard to l-arginine depletion. RESULTS: In both mouse tumors and cancer patients, MDSC expansion was associated with Arg activation causing accelerated l-arginine consumption. l-Arginine depletion in turn profoundly suppressed the capacity of classically activated macrophages to synthesize NO resulting in impaired tumor cell radiosensitivity. In advanced cT3-4 rectal cancer, circulating neutrophils revealed Arg overexpression approaching that in MDSC, therefore mounting a protumor compartment wherein Arg(+) neutrophils increased from 17% to over 90%. CONCLUSIONS: Protumor Arg(+) MDSC reveal a unique ability to radioprotect tumor cells through l-arginine depletion, a common mechanism behind both T-cell and macrophage inhibition. PMID- 26874545 TI - Reducing the population requiring interventions against lymphatic filariasis in Africa. PMID- 26874546 TI - Incidence, Characteristics, Risk Factors, and Outcomes of Takotsubo Cardiomyopathy With and Without Ventricular Arrhythmia. AB - Takotsubo cardiomyopathy (TC) is a medical entity mimicking an acute coronary syndrome (ACS). Ventricular arrhythmia (VA) in TC has been reported in small studies, leading to uncertain knowledge of its incidence. We sought to describe the characteristics, incidence, predictive factors, and outcomes of VA in patients presenting with TC. Over a 12-year period, we reviewed all patients (n = 5,484) referred to our coronary care unit for a suspicion of ACS. TC was diagnosed in 90 patients according to the Mayo Clinic criteria. Incidence of VA among TC was 10%. In multivariate analysis, the factors significantly associated with an increased risk of VA were syncope (p = 0.007), age <55 years (p = 0.008), atypical TC (p = 0.04), a troponin I peak >7 MUg/L (p = 0.04), and dobutamine use during hospitalization (p = 0.04). During follow-up, there was no significant difference in mortality rate between patients with or without VA. In conclusion, VA occurred in 10% of patients at the acute phase of TC and independent predictive factors of VA were syncope, atypical pattern of TC, high troponin peak, dobutamine use, and a relatively young age in a female and menopausal population. During the acute phase, identification of high-risk patients with VA allows better management, with electrocardiographic monitoring and therapeutic intervention in the coronary care unit. PMID- 26874547 TI - One-Year Results of Bioresorbable Vascular Scaffolds for Coronary Chronic Total Occlusions. AB - The potential of bioresorbable vascular scaffold (BVS) technology has been demonstrated in first-in-man studies with up to 5-year follow-up. This study sought to investigate the 1-year outcomes of the BVS, for the treatment of chronic total occlusions (CTOs), using various imaging techniques. Thirty-five true CTO lesions treated with BVS were included in this prospective study. Scaffolds were deployed after mandatory predilation and intravascular ultrasound analysis. Optical coherence tomography was performed after BVS implantation and at 10 to 12 months. Multislice computed tomography was performed at baseline and at 6 to 8 months. Mean patient age was 61 +/- 10 years. The most frequent vessel treated was the right coronary artery (46%). Lesions were classified as intermediate (49%) or difficult/very difficult (26%) according to the Japanese CTO complexity score. Predilation was performed in 100% of lesions, using cutting balloons in 71% of these. The total scaffold length implanted per lesion was of 52 +/- 23 mm. All scaffolds were delivered and deployed successfully. Postdilation was undertaken in 63%. By multislice computed tomography at 6 months, we observed 2 cases of asymptomatic scaffold restenosis, subsequently confirmed by angiography. At 12 months, no scaffold thrombosis or major adverse cardiac events were reported. The optical coherence tomography at follow-up showed that 94% of struts were well apposed and covered (5% of uncovered struts and 1% of nonapposed struts), and only 0.6% of struts were nonapposed and uncovered. In conclusion, 1-year results suggest that BVS for CTO is associated with excellent clinical and imaging outcomes. Accurate percutaneous coronary BVS technique might have enabled these promising results. PMID- 26874549 TI - Relation Between Red Blood Cell Distribution Width and Venous Thrombosis. PMID- 26874548 TI - Relation of Atrial Fibrillation in Acute Myocardial Infarction to In-Hospital Complications and Early Hospital Readmission. AB - Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) and contributes to high rates of in-hospital adverse events. However, there are few contemporary studies examining rates of AF in the contemporary era of AMI or the impact of new-onset AF on key in-hospital and postdischarge outcomes. We examined trends in AF in 6,384 residents of Worcester, Massachusetts, who were hospitalized with confirmed AMI during 7 biennial periods between 1999 and 2011. Multivariate logistic regression analysis was used to examine associations between occurrence of AF and various in-hospital and postdischarge complications. The overall incidence of AF complicating AMI was 10.8%. Rates of new-onset AF increased from 1999 to 2003 (9.8% to 13.2%), and decreased thereafter. In multivariable adjusted models, patients developing new-onset AF after AMI were at a higher risk for in-hospital stroke (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.6 to 4.1), heart failure (OR 2.0, 95% CI 1.7 to 2.4), cardiogenic shock (OR 3.7, 95% CI 2.8 to 4.9), and death (OR 2.3, 95% CI 1.9 to 3.0) than patients without AF. Development of AF during hospitalization for AMI was associated with higher rates of readmission within 30 days after discharge (21.7% vs 16.0%), but no significant difference was noted in early postdischarge 30-day all-cause mortality rates (8.3% vs 5.1%). In conclusion, new-onset AF after AMI is strongly related to in-hospital complications of AMI and higher short-term readmission rates. PMID- 26874551 TI - Temporal trends of persistent organic pollutant concentrations in precipitation around the Great Lakes. AB - The concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and several chlorinated insecticides in precipitation have been measured in samples collected every month since 1997 at six sites on the shores of the North American Great Lakes. We report here the geometric mean concentrations for each of these compounds for each year and at each site. Assuming a first-order rate decline for these data, we have calculated the time it takes for these concentrations to decrease by half. The halving times are not statistically distinguishable among the sites. Overall, the observed halving times are 11 +/- 2 years for the PCBs, 14 +/- 3 years for the PAHs, 4.0 +/- 0.2 for the hexachlorocyclohexanes, 8.0 +/- 0.9 for the DDTs, 5.1 +/- 0.8 for the chlordanes, and 8.4 +/- 0.6 for the endosulfans. In general, the halving times calculated from precipitation concentrations agree with those calculated from atmospheric vapor and particle phase concentrations. PMID- 26874550 TI - Temporal trends of Persistent Organic Pollutants (POPs) in arctic air: 20 years of monitoring under the Arctic Monitoring and Assessment Programme (AMAP). AB - Temporal trends of Persistent Organic Pollutants (POPs) measured in Arctic air are essential in understanding long-range transport to remote regions and to evaluate the effectiveness of national and international chemical control initiatives, such as the Stockholm Convention (SC) on POPs. Long-term air monitoring of POPs is conducted under the Arctic Monitoring and Assessment Programme (AMAP) at four Arctic stations: Alert, Canada; Storhofdi, Iceland; Zeppelin, Svalbard; and Pallas, Finland, since the 1990s using high volume air samplers. Temporal trends observed for POPs in Arctic air are summarized in this study. Most POPs listed for control under the SC, e.g. polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethanes (DDTs) and chlordanes, are declining slowly in Arctic air, reflecting the reduction of primary emissions during the last two decades and increasing importance of secondary emissions. Slow declining trends also signifies their persistence and slow degradation under the Arctic environment, such that they are still detectable after being banned for decades in many countries. Some POPs, e.g. hexachlorobenzene (HCB) and lighter PCBs, showed increasing trends at specific locations, which may be attributable to warming in the region and continued primary emissions at source. Polybrominated diphenyl ethers (PBDEs) do not decline in air at Canada's Alert station but are declining in European Arctic air, which may be due to influence of local sources at Alert and the much higher historical usage of PBDEs in North America. Arctic air samples are screened for chemicals of emerging concern to provide information regarding their environmental persistence (P) and long-range transport potential (LRTP), which are important criteria for classification as a POP under SC. The AMAP network provides consistent and comparable air monitoring data of POPs for trend development and acts as a bridge between national monitoring programs and SC's Global Monitoring Plan (GMP). PMID- 26874552 TI - Evaluation of handwriting kinematics and pressure for differential diagnosis of Parkinson's disease. AB - OBJECTIVE: We present the PaHaW Parkinson's disease handwriting database, consisting of handwriting samples from Parkinson's disease (PD) patients and healthy controls. Our goal is to show that kinematic features and pressure features in handwriting can be used for the differential diagnosis of PD. METHODS AND MATERIAL: The database contains records from 37 PD patients and 38 healthy controls performing eight different handwriting tasks. The tasks include drawing an Archimedean spiral, repetitively writing orthographically simple syllables and words, and writing of a sentence. In addition to the conventional kinematic features related to the dynamics of handwriting, we investigated new pressure features based on the pressure exerted on the writing surface. To discriminate between PD patients and healthy subjects, three different classifiers were compared: K-nearest neighbors (K-NN), ensemble AdaBoost classifier, and support vector machines (SVM). RESULTS: For predicting PD based on kinematic and pressure features of handwriting, the best performing model was SVM with classification accuracy of Pacc=81.3% (sensitivity Psen=87.4% and specificity of Pspe=80.9%). When evaluated separately, pressure features proved to be relevant for PD diagnosis, yielding Pacc=82.5% compared to Pacc=75.4% using kinematic features. CONCLUSION: Experimental results showed that an analysis of kinematic and pressure features during handwriting can help assess subtle characteristics of handwriting and discriminate between PD patients and healthy controls. PMID- 26874553 TI - Letter to Editor re Pavlovic et al. (2015). PMID- 26874554 TI - Assessment of voice, speech, and related quality of life in advanced head and neck cancer patients 10-years+ after chemoradiotherapy. AB - OBJECTIVES: Assessment of long-term objective and subjective voice, speech, articulation, and quality of life in patients with head and neck cancer (HNC) treated with concurrent chemoradiotherapy (CRT) for advanced, stage IV disease. MATERIALS AND METHODS: Twenty-two disease-free survivors, treated with cisplatin based CRT for inoperable HNC (1999-2004), were evaluated at 10-years post treatment. A standard Dutch text was recorded. Perceptual analysis of voice, speech, and articulation was conducted by two expert listeners (SLPs). Also an experimental expert system based on automatic speech recognition was used. Patients' perception of voice and speech and related quality of life was assessed with the Voice Handicap Index (VHI) and Speech Handicap Index (SHI) questionnaires. RESULTS: At a median follow-up of 11-years, perceptual evaluation showed abnormal scores in up to 64% of cases, depending on the outcome parameter analyzed. Automatic assessment of voice and speech parameters correlated moderate to strong with perceptual outcome scores. Patient-reported problems with voice (VHI>15) and speech (SHI>6) in daily life were present in 68% and 77% of patients, respectively. Patients treated with IMRT showed significantly less impairment compared to those treated with conventional radiotherapy. CONCLUSION: More than 10-years after organ-preservation treatment, voice and speech problems are common in this patient cohort, as assessed with perceptual evaluation, automatic speech recognition, and with validated structured questionnaires. There were fewer complaints in patients treated with IMRT than with conventional radiotherapy. PMID- 26874555 TI - Relation between soft tissue and skeletal changes after mandibular setback surgery: A systematic review and meta-analysis. AB - Accurate prediction of hard and soft tissue changes is essential in orthognathic surgery. The aim of the present study was to systematically investigate the relation between soft and hard tissue relocation after mandibular setback surgery. A systematic search was performed, correlation coefficients and ratios were retrieved from the eligible studies, and the risk of bias was assessed. The random effects method was used to combine data. The five eligible studies showed that sagittal changes in pogonion, point B, and incision inferius incisalis are highly correlated with respective soft tissue movements and exhibit ratios ranging from 0.915 to 1.051. Only two studies were classified as having a moderate risk of bias. Although the characteristics of the included data limit the formation of definite conclusions, the soft to hard tissue movement ratios produced constitute initial clinically relevant guidance. Further long-term standardized and well-conducted trials are needed. PMID- 26874556 TI - Impact of different sedation protocols and perioperative procedures on patients admitted to the intensive care unit after maxillofacial tumor surgery of the lower jaw: A retrospective study. AB - Maxillofacial tumor surgery often necessitates prolonged invasive ventilation to prevent blockage of the respiratory tract. To tolerate ventilation, continuously administered sedatives are recommended. Half-time of sedative or analgesic medication is an important characteristic by which narcotic drugs are chosen, due to the fact that weaning period increases with half-time. The aim of our study was to investigate whether a change in sedation regimen would affect the length of invasive ventilation or intensive care unit stay and medical costs. Additionally, the impact of various surgical procedures was analyzed. Data of 157 patients after mandibular surgery were retrospectively analyzed over 5 years in count regression models. Of those patients, 84 received a sedation regimen with sufentanil and midazolam and 73 with remifentanil and propofol. The impact of the surgical procedures (tracheostomy, tumor resection, neck dissection and length of operation) and the patient age and sex were analyzed with respect to length of ventilation and ICU days. Cost savings were calculated. Our data show that patients receiving remifentanil/propofol had fewer ventilation days (2.5 +/- 2.5 versus 6.1 +/- 4.6 days, P < 0.001) and were discharged earlier from the intensive care unit than patients receiving sufentanil/midazolam (5.1 +/- 3.8 versus 9.2 +/- 6.2 days, P < 0.001), leading to calculated cost savings of about 8000 Euro per patient. Length of operation negatively influenced length of ICU stay (P < 0.001). In conclusion, short-acting drugs such as remifentanil/propofol, as well as tracheostoma and shortened surgery duration may reduce the postoperative need for invasive ventilation and length of intensive care unit stay. PMID- 26874557 TI - Effects of oral clonidine premedication on hemodynamic status in bimaxillary orthognathic surgery: A double-blind randomized clinical trial. AB - PURPOSE: Controlled hypotension during a surgical procedure is a way to decrease blood pressure and subsequently to improve the field of operation. Clonidine is an antihypertensive agent used for induced hypotension. Correction of maxillomandibular discrepancies may necessitate performing osteotomy on both jaws in many cases. Bimaxillary orthognathic surgery is a procedure that is associated with significant blood loss. MATERIAL AND METHODS: A total of 30 participants who were candidates for double-jaw orthognathic surgery were classified into two groups with equal numbers. In one group, 300 MUg oral clonidine premedication was administered 90 min before the operation, and in the other group a placebo with the same condition as in the first group. Mean arterial pressure (MAP) and heart rate at 10 min intervals, operation time, blood loss, and surgeon satisfaction were measured. RESULTS: A total of 10 men and 5 women with a mean age of 22.9 +/- 2.9 years in the study group and 13 men and 2 women with a mean age of 22.1 +/- 2.1 years in the control group were evaluated. The MAP was significantly lower in the clonidine group (P < 0.001). Intraoperative bleeding was 508.67 +/- 46.2 mL in the placebo group and 287.33 +/- 72.06 mL in the clonidine group, and the difference was statistically significant (P < 0.05). Significant differences were observed in operation time (P < 0.05) and surgeon satisfaction (P < 0.001). CONCLUSION: The authors of this study suggest clonidine premedication in bimaxillary orthognathic surgery. Hemodynamic stability, bleeding control, decrease of operative time, and enhancement of surgical results are advantages of this method. PMID- 26874558 TI - The Motivational Interviewing Treatment Integrity Code (MITI 4): Rationale, Preliminary Reliability and Validity. AB - The Motivational Interviewing Treatment Integrity code has been revised to address new evidence-based elements of motivational interviewing (MI). This new version (MITI 4) includes new global ratings to assess clinician's attention to client language, increased rigor in assessing autonomy support and client choice, and items to evaluate the use of persuasion when giving information and advice. METHOD: Four undergraduate, non-professional raters were trained in the MITI and used it to review 50 audiotapes of clinicians conducting MI in actual treatments sessions. Both kappa and intraclass correlation indices were calculated for all coders, for the best rater pair and for a 20% randomly selected sample from the best rater pair. RESULTS: Reliability across raters, with the exception of Emphasize Autonomy and % Complex Reflections, were in the good to excellent range. Reliability estimates decrease when smaller samples are used and when fewer raters contribute. CONCLUSION: The advantages and drawbacks of this revision are discussed including implications for research and clinical applications. The MITI 4.0 represents a reliable method for assessing the integrity of MI including both the technical and relational components of the method. PMID- 26874559 TI - Ghrelin activates hypophysiotropic corticotropin-releasing factor neurons independently of the arcuate nucleus. AB - Previous work has established that the hormone ghrelin engages the hypothalamic pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of gamma-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID- 26874562 TI - Diurnal cortisol variation and cortisol response to an MRI stressor in schizophrenia and bipolar disorder. AB - Markers of HPA axis function, including diurnal cortisol rhythm and cortisol responses to stress or pharmacological manipulation, are increasingly reported as disrupted in schizophrenia (SZ) and bipolar disorder (BD). However, there has been no direct comparison of cortisol responses to stress in SZ and BD in the same study, and associations between cortisol dysfunction and illness characteristics remain unclear. In this study we used spline embedded linear mixed models to examine cortisol levels of SZ and BD participants at waking, during the first 45min after waking (representing the cortisol awakening response; CAR), during the period of rapid cortisol decline post the awakening response, and in reaction to a stressor (MRI scan), relative to healthy controls (HC). Contrary to expectations, neither SZ nor BD showed differences in waking cortisol levels, CAR, or immediate post-CAR decline compared to HC; however, waking cortisol levels were greater in BD relative to SZ. In response to the MRI stressor, the SZ group showed a significant absence of the expected increase in cortisol responsivity to stress, which was seen in both the BD and HC groups. Clinical factors affecting the CAR differed between SZ and BD. In SZ, higher antipsychotic medication dosage was associated with a steeper incline of the CAR, while greater positive symptom severity was associated with a more blunted CAR, and greater levels of anxiety were associated with the blunted cortisol response to stress. In BD, longer illness duration was associated with a steeper incline in CAR and lower levels of waking cortisol. These results suggest that cortisol responses may normalize with medication (in SZ) and longer illness duration (in BD), in line with findings of aberrant cortisol levels in the early stages of psychotic disorders. PMID- 26874561 TI - Exposure to acute stress enhances decision-making competence: Evidence for the role of DHEA. AB - Exposure to acute stress can impact performance on numerous cognitive abilities, but little is known about how acute stress affects real-world decision-making ability. In the present study, we induced acute stress with a standard laboratory task involving uncontrollable socio-evaluative stress and subsequently assessed decision-making ability using the Adult Decision Making Competence index. In addition, we took baseline and post-test saliva samples from participants to examine associations between decision-making competence and adrenal hormones. Participants in the stress induction group showed enhanced decision-making competence, relative to controls. Further, although both cortisol and dehydroepiandrosterone (DHEA) reactivity predicted decision-making competence when considered in isolation, DHEA was a significantly better predictor than cortisol when both hormones were considered simultaneously. Thus, our results show that exposure to acute stress can have beneficial effects on the cognitive ability underpinning real-world decision-making and that this effect relates to DHEA reactivity more than cortisol. PMID- 26874560 TI - Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling. AB - Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system. PMID- 26874563 TI - Recurrence of stroke caused by nocturnal hypoxia-induced blood pressure surge in a young adult male with severe obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome (OSAS) causes resistant hypertension and a hypopnea-related nocturnal blood pressure (BP) surge. This could lead to an increase of not only the nocturnal BP level but also nocturnal BP variability, both of which increase an individual's cardiovascular risk. We recently developed a trigger sleep BP monitoring method that initiates BP measurement when an individual's oxygen desaturation falls below a variable threshold, and we demonstrated that it can detect a BP surge during apnea episodes. We here report the case of a 36-year-old man with severe OSAS who experienced the recurrence of stroke due to nocturnal hypoxia and a nocturnal BP surge measured by this trigger sleep BP monitoring device. A nocturnal BP surge during sleep in OSAS patients could be a strong trigger of cardiovascular events. PMID- 26874564 TI - Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: pathophysiological hypothesis. AB - Primarily the sodium-glucose cotransporter 2 (SGLT2) inhibitors suppress the cotransport of glucose and sodium from the tubular lumen of proximal tubules to the blood and enhance the glucose excretion into urine. Therefore, glucose and caloric balances become negative, making the blood glucose level as well as insulin secretion both reduced. On the other hand, the proximal tubular fluid, constituting with low chloride concentration because of SGLT2 inhibition, is transferred to the loop of Henle. On the low chloride conditions, the reabsorption mechanisms in the loop of Henle do not work, as if loop diuretics are given. Finally, blood pressure is also lowered secondarily due to the loop diuretic action by SGLT2 inhibitions. Thus, the metabolic and hemodynamic combined systems synergistically interact further to suppress the risks leading to atherosclerosis and organs damage. Precise mechanisms for SGLT2 inhibitors to work in various aspects especially in preventing organ damage and cardiovascular events must be clarified further. PMID- 26874565 TI - ST-segment abnormalities are associated with long-term prognosis in non-ST segment elevation acute coronary syndromes: The ERICO-ECG study. AB - INTRODUCTION: We aimed to identify whether ST-segment abnormalities, in the admission or during in-hospital stay, are associated with survival and/or new incident myocardial infarction (MI) in 623 non-ST-elevation acute coronary syndrome participants of the Strategy of Registry of Acute Coronary Syndrome (ERICO) study. MATERIALS AND METHODS: ERICO is conducted in a community-based hospital. ST-segment analysis was based on the Minnesota Code. We built Cox regression models to study whether ECG was an independent predictor for clinical outcomes. RESULTS: Median follow-up was 3years. We found higher risk of death due to MI in individuals with ST-segment abnormalities in the final ECG (adjusted hazard ratio: 2.68; 95% confidence interval: 1.14-6.28). Individuals with ST segment abnormalities in any tracing had a non-significant trend toward a higher risk of fatal or new non-fatal MI (p=0.088). CONCLUSIONS: ST-segment abnormalities after the initial tracing added long-term prognostic information. PMID- 26874567 TI - Clinical, biochemical, and molecular findings in a Colombian patient with Tay Sachs disease. PMID- 26874566 TI - Beat-to-beat determinants of the beat-to-beat temporal and spatial variability of repolarization. AB - BACKGROUND: The goal of this study was to compare the time series predictors of beat-to-beat variability in repolarization in healthy individuals. METHODS: Spatial QRS- and T-vector amplitudes, spatial QRS-T, RR' and TT' angles, RR' and QT intervals, and QRS- and T-loop roundness were measured on 453 consecutive sinus beats in 168 healthy subjects (mean age 39.8+/-15.6years; 50% men; 93% white). Panel time-series regression models were adjusted by age, sex, and race. Appropriate time series of ECG metrics served as predictors and outcomes. RESULTS: Increase in T-loop roundness index by 0.1 was associated with 1.1 degrees (95%CI 0.9-2.2; P=0.048) increase in corresponding TT' angle. One unit increase in a respiration index was associated with 4ms (95%CI 0.6-7.0; P=0.021) increase in QT interval. CONCLUSIONS: Spatial TT' angle and beat-to-beat variability in T-loop roundness represent intrinsic measures of repolarization variability. QT interval variability characterizes the effect of respiration and heart rate variability. PMID- 26874568 TI - Hereditary neuropathy with liability to pressure palsy presenting as a bilateral brachial plexopathy. PMID- 26874569 TI - Toxic hepatitis after concomitant interferon beta and aloe vera treatment in a patient with multiple sclerosis: A case report. PMID- 26874570 TI - Retrospective multicentre observational study on clinical management and treatment of different types of status epilepticus in clinical practice. AB - INTRODUCTION: Status epilepticus (SE) is a neurological emergency associated with significant mortality and morbidity. We analyse characteristics of this entity in our population. METHODS: Data from electronic medical records of adults diagnosed with SE were collected retrospectively from 5 hospitals over 4 years. RESULTS: Data reflected 84 episodes of SE in 77 patients with a mean age of 60.3 years. Of this sample, 52.4% had a previous history of epilepsy. Status classification: 47.6% tonic-clonic, 21.4% complex partial, 17.9% partial motor, 6% partial simple, 3.6% myoclonic, and 3.6% subtle SE. Based on the duration of the episode, SE was defined in this study as early stage (up to 30min) in 13.1%, established (30-120min) in 20.2%, refractory (more than 120min) in 41.7%, and super refractory (episodes continuing or recurring after more than 24h of anaesthesia) in 13.1%. Ten patients (11.9%) died when treatment failed to control SE. The cumulative percentage of success achieved was 8.3% with the first treatment, 27.3% for the second, 48.7% for the third, 58.2% for the fourth, 70.1% for the fifth, 80.8% for the sixth, 83.2% for the seventh, and 84.4% for the eighth. CONCLUSIONS: In our study, we found that SE did not respond to treatment within 2h in approximately half the cases and 11.9% of the patients died without achieving seizure control, regardless of the type of status. Half the patients responded by the third treatment but some patients needed as many as 8 treatments to resolve seizures. Using large registers permitting analysis of the different types and stages of SE is warranted. PMID- 26874571 TI - Recurrent diaphoresis, acute confusional state, and pleural mesothelioma. PMID- 26874573 TI - Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study. AB - We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID- 26874572 TI - Diagnostic value of IMP3 and mesothelin in differentiating pancreatic ductal adenocarcinoma from chronic pancreatitis. AB - BACKGROUND: The discrimination between pancreatic ductal adenocarcinoma (PDA) and chronic pancreatitis may be confusing at both clinical and radiologic levels. So, the search for biomarkers able to distinguish both clinical conditions is of great interest. AIM: This study was undertaken to assess the value of insulin like growth factor II mRNA binding protein 3 (IMP3) and mesothelin to differentiate PDA from non-neoplastic/reactive pancreatic duct epithelium. METHODS: Immunohistochemical staining for IMP3 and mesothelin was performed on 40 formalin-fixed, paraffin-embedded tissue sections of PDA, 20 biopsies of chronic pancreatitis and 10 normal pancreatic tissue obtained from tumor-free surgical margins. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy were calculated. RESULTS: IMP3 immunoreactivity was observed in 34 of 40 (85%) cases of PDA. The staining reaction was moderate to strong in 30 (75%) cases and diffuse in 26 (65%) cases. Eighteen of 20 (90%) biopsies of chronic pancreatitis were negative for IMP3, while the other two cases (10%) showed weak and focal IMP3 immunoreactivity. On the other hand, mesothelin demonstrated positive immunoreactivity in 30 of 40 (75%) cases of PDA. The staining reaction was moderate to strong in 24 (60%) cases and diffuse in 22 (55%) cases. Sixteen of 20 (80%) biopsies of chronic pancreatitis were negative for mesothelin, while weak and focal mesothelin staining was detected in the other 4 cases. All normal pancreatic tissues were negative for IMP3 and mesothelin expression. IMP3 showed higher sensitivity (85%) and specificity (90%) than mesothelin (75% and 80%, respectively). CONCLUSIONS: Our results showed that IMP3 immunostaining has a higher sensitivity and specificity than mesothelin for the diagnosis of PDA. IMP3 and mesothelin may be useful markers in distinguishing neoplastic from reactive lesions of the pancreas in instances where this is impossible by morphology alone in surgical pathology practice. PMID- 26874574 TI - Diagnostic value of a semi-nested PCR for the diagnosis of mucormycosis and aspergillosis from paraffin-embedded tissue: A single center experience. AB - OBJECTIVE: The main aim of our study was to investigate the diagnostic value of a molecular method for the diagnosis of mucormycosis and aspergillosis from formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: A retrospective chart review identified all cases with histology reports mentioning the presence of fungi with morphological characteristics of either Aspergillus or mucormycetes, for the period 2005-2012. Paraffin blocks were retrieved from the archives of the Department of Pathology. A semi-nested PCR specific for the detection of mucormycetes and Aspergillus species was applied in FFPE tissue from the above blocks. Results were compared with those of histological (gold standard) and microbiological methods. RESULTS: Twenty cases with fungal hyphae in tissue were revealed. Mucormycetes were detected in 9 cases (45%) by PCR, in only 4 of which culture was available. Species of Aspergillus were detected in 8 cases (40%) by PCR, two of which were co-infection with mucormycetes. Five patients had other fungi, non-detectable with this specific PCR. At least one sample per patient was positive by PCR. Seven out of 30 samples tested overall were false negative. The calculated sensitivity of this method in our setting was 79.3% (95% CI: 60.3-91.9%); specificity was 100%. CONCLUSIONS: The specific PCR used appears to be an easy and useful tool for the prompt and accurate diagnosis of mucormycosis and aspergillosis, in combination with histology and direct examination. Mucormycosis was more frequent than aspergillosis during the study period, highlighting the importance of continuous epidemiological surveillance of these serious infections. PMID- 26874577 TI - Attention and spatial cognition: Neural and anatomical substrates of visual neglect. AB - Unilateral spatial neglect (USN) is a neurological disorder often observed following damage to the right cerebral hemisphere. Patients with USN are no longer able to take into account stimuli presented on the left side of space. In this article, we will discuss the neuroanatomical correlates that underlie visuospatial attention and can cause USN, an area of growing research interest in the past 20 years. This syndrome has often been related to cortical damage, notably in the inferior parietal lobule. Other data have also implicated lesions in the inferior frontal gyrus or the superior temporal gyrus. In this article, we will highlight the relevance of viewing USN as a disconnection syndrome of interconnected cerebral areas, as opposed to a focal cortical syndrome. We will review data that provide evidence of intrahemispheric disconnection, in particular within the right hemisphere's frontoparietal networks connected by the superior longitudinal fasciculus. Recent findings suggest that interhemispheric disconnection could also contribute to the manifestations of USN. Most importantly, interhemispheric disconnection might be a predictive factor for the chronicity of this disorder. This hypothesis implies that the left hemisphere by itself is not able to compensate for the patients' deficits. Recovery requires the ability to exchange information between the two hemispheres, particularly in the posterior parietal and occipital regions. PMID- 26874576 TI - Diabetes, Gray Matter Loss, and Cognition in the Setting of Parkinson Disease. AB - RATIONALE AND OBJECTIVES: Parkinson disease (PD) is a progressive neurodegenerative disorder affecting motor and cognitive functions. Prior studies showed that patients with PD and diabetes (DM) demonstrate worse clinical outcomes compared to nondiabetic subjects with PD. Our study aimed at defining the relationship between DM, gray matter volume, and cognition in patients with PD. MATERIALS AND METHODS: This study included 36 subjects with PD (12 with DM, 24 without DM, mean age = 66). Subjects underwent high-resolution T1-weighted brain magnetic resonance imaging, [(11)C]dihydrotetrabenazine positron emission tomography imaging to quantify nigrostriatal dopaminergic denervation, clinical, and cognitive assessments. Magnetic resonance images were postprocessed to determine total and lobar cortical gray matter volumes. Cognitive testing scores were converted to z-scores for specific cognitive domains and a composite global cognitive z-score based on normative data computed. Analysis of covariance, accounting for effects of age, gender, intracranial volume, and striatal [(11)C]dihydrotetrabenazine binding, was used to test the relationship between DM and gray matter volumes. RESULTS: Impact of DM on total gray matter volume was significant (P = 0.02). Post hoc analyses of lobar cortical gray matter volumes revealed that DM was more selectively associated with lower gray matter volumes in the frontal regions (P = 0.01). Cognitive post hoc analyses showed that interaction of total gray matter volume and DM status was significantly associated with composite (P = 0.007), executive (P = 0.02), and visuospatial domain cognitive z-scores (P = 0.005). These associations were also significant for the frontal cortical gray matter. CONCLUSION: DM may exacerbate brain atrophy and cognitive functions in PD with greater vulnerability in the frontal lobes. Given the high prevalence of DM in the elderly, delineating its effects on patient outcomes in the PD population is of importance. PMID- 26874575 TI - Emerging Complexities in Adipocyte Origins and Identity. AB - The global incidence of obesity and its comorbidities continues to rise along with a demand for novel therapeutic interventions. Brown adipose tissue (BAT) is attracting attention as a therapeutic target because of its presence in adult humans and high capacity to dissipate energy as heat, and thus burn excess calories, when stimulated. Another potential avenue for therapeutic intervention is to induce, within white adipose tissue (WAT), the formation of brown-like adipocytes called brite (brown-like-in-white) or beige adipocytes. However, understanding how to harness the potential of these thermogenic cells requires a deep understanding of their developmental origins and regulation. Recent cell labeling and lineage-tracing experiments are beginning to shed light on this emerging area of adipocyte biology. We review here adipocyte development, giving particular attention to thermogenic adipocytes. PMID- 26874578 TI - Optic ataxia in Balint-Holmes syndrome. AB - The objective of this review is to reinstate the diversity of visual perception and visuomotor symptoms following lesions to the posterior parietal cortex (dorsal visual stream). This diversity was overshadowed for a long time and shows the contribution of the dorsal visual stream not only to action but also to perception. More precisely, we propose that the visuomotor deficit in optic ataxia stems from two distinct components: visual proprioceptive deficit (hand effect) and visual attentional deficit (field effect) also affecting the perception in peripheral vision. PMID- 26874579 TI - Eosinophil chemotaxis assay in nasal polyps by using a novel optical device EZ TAXIScan: Role of CC-chemokine receptor 3. AB - BACKGROUND: The chemokine receptor, CC-chemokine receptor 3 (CCR3), and its major ligands, eotaxin, RANTES, and MCP-4, are involved in eosinophil chemotaxis. It is thought that CCR3 plays an important role in the recruitment and activation of eosinophils in nasal polyposis. We examined nasal polyp extract-induced eosinophil chemotaxis and the effect of a CCR3 antagonist using EZ-TAXIScan, a novel real-time chemotaxis assay device. METHODS: Nasal polyps were obtained from chronic rhinosinusitis (CRS) patients during surgery. The polyps were homogenized and eotaxin levels in the extracts were measured. Eosinophils were purified from human peripheral blood by the CD16 negative selection method. Nasal polyp extract induced eosinophil chemotaxis, with or without CCR3 antagonist, was assessed by EZ-TAXIScan. RESULTS: There was a significant positive correlation between the eosinophil counts in nasal polyp and eotaxin levels in the nasal polyp extracts. Using EZ-TAXIScan, eosinophil chemotactic responses were observed following stimulation with nasal polyp extracts. There was a significant positive correlation between the chemotactic index toward the nasal polyp extracts and their eotaxin levels. Nasal polyp extract-induced chemotaxis was completely inhibited by CCR3 antagonist but not by chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist which inhibited PGD2-induced eosinophil chemotaxis. CONCLUSIONS: The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis. PMID- 26874580 TI - The diversity of circulating neutrophils in cancer. AB - Neutrophils, the most abundant leukocyte in human circulation are being more and more recognized as part of the immune reaction to cancer. In the last years, the understanding that neutrophils possess a dual role in cancer development has emerged. During tumor progression the number of neutrophils increase, and their phenotype change. In advanced cancer, we can find several sub-populations of circulating neutrophils possessing different characteristics of maturity, tumor cytotoxicity and immune suppression. One important sub-population of circulating neutrophils is the granulocytic myeloid derived suppressor cells (G-MDSC). Differencing G-MDSC from other sub-populations of neutrophils in the circulation is a complex and controversial task, as there are no clear definitions of the differences between these granulocytic sub-populations. Herein we review the differences described thus far between G-MDSC and other circulating neutrophils. We then compare the morphology, surface markers, function and prognostic importance of the different tumor-related circulating neutrophils, as described by us and others, and discuss the possible relations between the different sub populations, their source and fate. Lastly, we suggest a nomenclature to try and encompass the full range of circulating neutrophils in cancer. PMID- 26874582 TI - Primary signet ring cell carcinoma of the cervix: A case report and review of the literature. AB - INTRODUCTION: Primary signet cell carcinoma of the cervix has been reported only in 18 cases to date. PRESENTATION OF CASE: A 48-year-old woman was seen at our Gynecologic Oncology Unit, because she complained postcoital bleeding during the last three months. She had 1-2 cm cervical mass, originating from the endocervical canal. A biopsy revealed a signet ring cell-type adenocarcinoma. Suspected primary sites were excluded after gastroscopy, colonoscopy and mammography. The patient underwent a laparoscopic type-3 radical hysterectomy with bilateral salpingo-oophorectomy, pelvic lymph node dissection and paraaortic lymph node dissection with a presumed diagnosis of primary signet ring cell carcinoma of the cervix. Microscopically, the tumour consisted of 70% signet ring cell type and 30% endocervical adenocarcinoma. She did not receive any adjuvant treatment. Follow-up at 18 months after surgery showed no evidence of recurrence. DISCUSSION: Nineteenth case of a primary signet ring cell carcinoma of the cervix was presented. Immunohistochemical studies and HPV DNA positivity may help in diagnosis. CONCLUSION: It is crucial to differentiate primary tumour from metastatic signet cell carcinoma, while treatment and prognosis differ significantly. PMID- 26874581 TI - Lentiviral vector encoding ubiquitinated hepatitis B core antigen induces potent cellular immune responses and therapeutic immunity in HBV transgenic mice. AB - Predominant T helper cell type 1 (Th1) immune responses accompanied by boosted HBV-specific cytotoxic T lymphocyte (CTL) activity are essential for the clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. Ubiquitin (Ub) serves as a signal for the target protein to be recognized and degraded through the ubiquitin-proteasome system (UPS). Ubiquitinated hepatitis B core antigen (Ub-HBcAg) has been proved to be efficiently degraded into the peptides, which can be presented by major histocompatibility complex (MHC) class I resulting in stimulating cell-mediated responses. In the present study, lentiviral vectors encoding Ub-HBcAg (LV-Ub-HBcAg) were designed and constructed as a therapeutic vaccine for immunotherapy. HBcAg-specific cellular immune responses and anti-viral effects induced by LV-Ub-HBcAg were evaluated in HBV transgenic mice. We demonstrated that immunization with LV-Ub-HBcAg promoted the secretion of cytokines interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), generated remarkably high percentages of IFN-gamma-secreting CD8(+) T cells and CD4(+) T cells, and enhanced HBcAg specific CTL activity in HBV transgenic mice. More importantly, vaccination with LV-Ub-HBcAg could efficiently decreased the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA and the expression of HBsAg and HBcAg in liver tissues of HBV transgenic mice. In addition, LV-Ub-HBcAg could upregulate the expression of T cell-specific T-box transcription factor (T-bet) and downregulate the expression of GATA-binding protein 3 (GATA-3) in spleen T lymphocytes. The therapeutic vaccine LV-Ub-HBcAg could break immune tolerance, and induce potent HBcAg specific cellular immune responses and therapeutic effects in HBV transgenic mice. PMID- 26874583 TI - Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy: A case report. AB - INTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnostic. PMID- 26874584 TI - Endophthalmitis of probable endogenous origin caused by Scedosporium boydii: A case report. AB - BACKGROUND: Mycotic ocular infections caused by the Scedosporium apiospermum species complex are challenging to treat because of the delayed diagnoses and poor responses to antifungal drugs and surgical treatment. CASE REPORT: A case of a 69-year-old male patient with a history of diabetes mellitus type 2 and prior surgery on the right femur is described. In the 10 days prior to the ophthalmic consultation he started with ocular pain, adding to a previous and progressive loss of visual acuity in his right eye. The diagnosis of endophthalmitis of probable endogenous origin was established. Despite medical treatment, the patient's condition worsened and, due to the imminent risks, an enucleation was performed. Smears of the enucleation tissue revealed fungal cells, and the cultures yielded a fungus belonging to the S. apiospermum species complex, which was identified as Scedosporium boydii by morphological characteristics and sequencing of a PCR amplicon. CONCLUSIONS: A diagnosis of endophthalmitis of probable endogenous origin in the right eye was based on a previous right femur surgery. Potential risk to the patient led to enucleation. PMID- 26874585 TI - High rate of Candida deep-seated infection in patients under chronic hemodialysis with extended central venous catheter use. AB - BACKGROUND: Hemodialysis has been described as an important risk factor for the development of candidemia in patients suffering from chronic renal failure. AIMS: The aim of this study was to evaluate the epidemiology of candidemia in outpatients with renal replacement therapy (RRT) by hemodialysis where the fungemia clearly represents a healthcare-associated infection. METHODS: We retrospectively collected clinical and laboratory data from patients undergoing at least 3 months of RRT by hemodialysis who developed candidemia within 48h of hospital admission. RESULTS: We identified 14 patients with candidemia with central venous catheters (CVC) in place for 11-277 days before developing fungemia. Deep-seated infection was documented in 6 out of 14 candidiasis cases (43%), including 5 cases of endocarditis (36%). CONCLUSIONS: CVC in patients under RRT should be promptly replaced by fistulas and grafts to avoid bloodstream infections. Facing a case of candidemia, adequate source control and prompt initiation of antifungal therapy are mandatory to avoid morbidity and mortality. PMID- 26874586 TI - Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer. AB - Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. PMID- 26874587 TI - Replication cycle of duck hepatitis A virus type 1 in duck embryonic hepatocytes. AB - Duck hepatitis A virus type 1 (DHAV-1) is an important agent of duck viral hepatitis. Until recently, the replication cycle of DHAV-1 is still unknown. Here duck embryonic hepatocytes infected with DHAV-1 were collected at different time points, and dynamic changes of the relative DHAV-1 gene expression during replication were detected by real-time PCR. And the morphology of hepatocytes infected with DHAV was evaluated by electron microscope. The result suggested that the adsorption of DHAV-1 saturated at 90 min post-infection, and the virus particles with size of about 50 nm including more than 20 nm of vacuum drying gold were observed on the infected cells surface. What's more, the replication lasted around 13 h after the early protein synthesis for about 5h, and the release of DHAV-1 was in steady state after 32 h. The replication cycle will enrich the data for DVH control and provide the foundation for future studies. PMID- 26874589 TI - [Molluscum contagiosum due to vertical transmission]. PMID- 26874590 TI - What's Keeping Teenagers Up? Prebedtime Behaviors and Actigraphy-Assessed Sleep Over School and Vacation. AB - PURPOSE: Technology-related behaviors (e.g., computer use) before bedtime (BT) have been associated with poorer and shorter sleep in adolescents; however, less is known about other behaviors in relation to sleep. This study characterized a range of behaviors in the hour before bed (i.e., pre-BT behaviors [PBBs]) and examined their relationship with sleep parameters during school and vacation periods (i.e., restricted and extended sleep opportunities, respectively). Mechanistic roles of chronotype and cognitive presleep arousal (PSAcog) were also examined. METHODS: During the last week of a school term and throughout a 2-week vacation, 146 adolescents (47.26% male, age M +/- standard deviation = 16.2 +/- 1.0 years) from the general community completed daily sleep measure using actigraphy, self-report measures on PBBs and PSAcog (Presleep Arousal Scale) for both school and vacation periods, and chronotype (Morningness-Eveningness Questionnaire). RESULTS: Adolescents engaged in a variety of behaviors before bed. Notably, playing video games was associated with significantly later school and vacation BT and shorter school sleep duration (controlling for chronotype). During vacation, online social media was associated with significantly longer sleep onset latency, and this relationship was mediated by higher PSAcog. In contrast, on school nights, spending time with family was associated with significantly earlier BT and longer sleep duration. CONCLUSIONS: Technology related PBBs video games and online social media were risk factors for shorter and poorer sleep, whereas time with family was protective of sleep duration. In addressing sleep problems in adolescents, therapeutic procedures that target the potentially addictive nature of technology use and reduce PSAcog were implicated. PMID- 26874588 TI - Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets. AB - Control of influenza A virus (IAV) in pigs is done by vaccination of females to provide maternally-derived antibodies (MDA) through colostrum. Our aim was to evaluate if MDA interfere with IAV infection, clinical disease, and transmission in non-vaccinated piglets. In the first study, naive sows were vaccinated with H1N2-delta1 whole inactivated virus (WIV) vaccine. In a follow-up study seropositive sows to 2009 pandemic H1N1 (H1N1pdm09) were boosted with H1N1pdm09 WIV or secondary experimental infection (EXP). MDA-positive pigs were challenged with homologous or heterologous virus, and MDA-negative control groups were included. WIV-MDA piglets were protected from homologous infection. However, piglets with WIV-derived MDA subsequently challenged with heterologous virus developed vaccine associated enhanced respiratory disease (VAERD), regardless of history of natural exposure in the sows. Our data indicates that although high titers of vaccine-derived MDA reduced homologous virus infection, transmission, and disease, MDA alone was sufficient to induce VAERD upon heterologous infection. PMID- 26874591 TI - Assessing the associations among trait and state levels of deliberate and spontaneous mind wandering. AB - Recent research has demonstrated that mind wandering can be subdivided into spontaneous and deliberate types, and this distinction has been found to hold at both the trait and state levels. However, to date, no attempts have been made to link trait-level spontaneous and deliberate mind wandering with state-level assessments of these two subtypes of mind wandering. Here we evaluated whether trait-level deliberate and spontaneous mind wandering map onto state levels of these subtypes of mind wandering. Results showed correspondence between trait level reports of spontaneous and deliberate mind wandering and their state-level counterparts, indicating that people's reports on the intentionality of their mind wandering in the laboratory correspond to their reports of the intentionality of mind wandering in everyday life. Thus, the trait- and state level scales of mind wandering were found to validate each other: Whereas the state-level measures provided some construct validity for the trait-level measures, the trait-level measures indicated that the state-level measures may be generalizable to everyday situations. PMID- 26874592 TI - Assessment of volatile compounds, neutral and polar lipid fatty acids of four beef muscles from USDA Choice and Select graded carcasses and their relationships with consumer palatability scores and intramuscular fat content. AB - Fatty acids (FA) in neutral and polar lipids (NL and PL) and volatile compounds were determined in Gluteus medius (GM), Longissimus lumborum (LL), Serratus ventralis (SV), and Semimembranosus (SM) muscles from upper 2/3 USDA Choice and Select quality grades (QG). Concentrations of NL FA (mg/g) were influenced by intramuscular fat (IMF) content being greater in upper 2/3 Choice compared with Select. The SV contained greater concentrations of NL FA; meanwhile, the SM contained the lowest quantities of NL FA. Percentages (g/100g of total FA) of NL SFA and MUFA were increased in beef with greater IMF content. Concentrations and percentages of PL FA had muscle specific differences between QG. Volatile compounds were primarily affected by muscle. Increases in SFA and MUFA were related with consumer liking, regardless of lipid fraction. Overall the influence of QG on SFA and MUFA was muscle specific. Therefore, each muscle may require specific considerations when considering FA, volatile compounds, and ultimately consumer liking. PMID- 26874593 TI - The use of high pressure processing to enhance the quality and shelf life of reduced sodium naturally cured restructured cooked hams. AB - The combined effect of partial salt replacement with modified potassium chloride and high pressure processing (600 MPa for 3 min at 8 degrees C) on the quality and shelf life of naturally-cured restructured hams was investigated over a 12 week storage period. Instrumental, microbiological and consumer acceptability testing was performed. A partial salt substitution with modified potassium chloride adversely affected textural and water binding characteristics of hams and led to a decrease in the consumer acceptance compared to regular salt hams. Celery powder used as a curing agent had beneficial effects on water holding and moisture retention and improved bind of restructured hams; however the consumer acceptability of flavor and aftertaste received significantly lower scores compared to nitrite. No significant differences in all consumer acceptability parameters resulted for hams subjected to HPP compared to non-HPP for all storage periods indicating that HPP can effectively extend shelf-life of restructured ham without compromising eating quality. PMID- 26874594 TI - Online monitoring of red meat color using hyperspectral imaging. AB - A hyperspectral imaging system in the spectral range of 400-1000 nm was tested to develop an online monitoring system for red meat (beef, lamb, and pork) color in the meat industry. Instead of selecting different sets of important wavelengths for beef, lamb, and pork, a set of feature wavelengths were selected using the successive projection algorithm for red meat colors (L*, a*, b) for convenient industrial application. Only six wavelengths (450, 460, 600, 620, 820, and 980 nm) were further chosen as predictive feature wavelengths for predicting L*, a*, and b* in red meat. Multiple linear regression models were then developed and predicted L*, a*, and b* with coefficients of determination (R(2)p) of 0.97, 0.84, and 0.82, and root mean square error of prediction of 1.72, 1.73, and 1.35, respectively. Finally, distribution maps of meat surface color were generated. The results indicated that hyperspectral imaging has the potential to be used for rapid assessment of meat color. PMID- 26874596 TI - Does the benefits schedule of cash assistance programs affect the purchase of temptation goods? Evidence from Peru. AB - A critique of cash assistance programs is that beneficiaries may spend the money on "temptation goods" such as alcohol and tobacco. We exploit a change in the payment schedule of Peru's conditional cash transfer program to identify the impact of benefit receipt frequency on the purchase of temptation goods. We use annual household data among cross-sectional and panel samples to analyze the effect of the policy change on the share of the household budget devoted to four categories of temptation goods. Using a difference-in-differences estimation approach, we find that larger, less frequent payments increased the expenditure share of alcohol by 55-80% and sweets by 10-40%, although the absolute magnitudes of these effects are small. Our study suggests that less frequent benefits scheduling may lead cash recipients to make certain types of temptation purchases. PMID- 26874595 TI - Inequalities in dementia incidence between six racial and ethnic groups over 14 years. AB - INTRODUCTION: Reducing racial/ethnic disparities is a primary objective of the National Alzheimer's Plan (NAPA), yet direct comparisons within large samples representing diversity of the United States are lacking. METHODS: Dementia incidence from January 1, 2000 to December 31, 2013 and a 25-year cumulative risk in 274,283 health care members aged 64+ (n = 18,778 African-American, n = 4543 American Indian/Alaska Native [AIAN], n = 21,000 Latino, n = 440 Pacific Islander, n = 206,490 white, n = 23,032 Asian-Americans). Cox proportional hazard models were adjusted for age, sex, medical utilization, and comorbidities. RESULTS: Dementia incidence (n = 59,555) was highest for African-Americans (26.6/1000 person-years) and AIANs (22.2/1000 person-years); intermediate for Latinos (19.6/1000 person-years), Pacific Islanders (19.6/1000 person-years), and whites (19.3/1000 person-years) and lowest among Asian-Americans (15.2/1000 person-years). Risk was 65% greater for African-Americans (hazard ratio = 1.65; 95% confidence interval = 1.58-1.72) versus Asian-Americans. Cumulative 25-year risk at age 65 was as follows: 38% African-Americans, 35% AIANs, 32% Latino, 25% Pacific Islanders, 30% white, and 28% Asian-Americans. DISCUSSION: Dementia rates varied over 60% between groups, providing a comprehensive benchmark for the NAPA goal of reducing disparities. PMID- 26874597 TI - ASGE Technology Committee systematic review and meta-analysis assessing the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations thresholds for adopting real-time imaging-assisted endoscopic targeted biopsy during endoscopic surveillance of Barrett's esophagus. AB - BACKGROUND AND AIMS: Endoscopic real-time imaging of Barrett's esophagus (BE) with advanced imaging technologies enables targeted biopsies and may eliminate the need for random biopsies to detect dysplasia during endoscopic surveillance of BE. This systematic review and meta-analysis was performed by the American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee to specifically assess whether acceptable performance thresholds outlined by the ASGE Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) document for clinical adoption of these technologies have been met. METHODS: We conducted meta-analyses calculating the pooled sensitivity, negative predictive value (NPV), and specificity for chromoendoscopy by using acetic acid and methylene blue, electronic chromoendoscopy by using narrow-band imaging, and confocal laser endomicroscopy (CLE) for the detection of dysplasia. Random effects meta-analysis models were used. Statistical heterogeneity was evaluated by means of I(2) statistics. RESULTS: The pooled sensitivity, NPV, and specificity for acetic acid chromoendoscopy were 96.6% (95% confidence interval [CI], 95-98), 98.3% (95% CI, 94.8-99.4), and 84.6% (95% CI, 68.5-93.2), respectively. The pooled sensitivity, NPV, and specificity for electronic chromoendoscopy by using narrow-band imaging were 94.2% (95% CI, 82.6-98.2), 97.5% (95% CI, 95.1-98.7), and 94.4% (95% CI, 80.5-98.6), respectively. The pooled sensitivity, NPV, and specificity for endoscope-based CLE were 90.4% (95% CI, 71.9-97.2), 98.3% (95% CI, 94.2-99.5), and 92.7% (95% CI, 87-96), respectively. CONCLUSIONS: Our meta-analysis indicates that targeted biopsies with acetic acid chromoendoscopy, electronic chromoendoscopy by using narrow-band imaging, and endoscope-based CLE meet the thresholds set by the ASGE PIVI, at least when performed by endoscopists with expertise in advanced imaging techniques. The ASGE Technology Committee therefore endorses using these advanced imaging modalities to guide targeted biopsies for the detection of dysplasia during surveillance of patients with previously nondysplastic BE, thereby replacing the currently used random biopsy protocols. PMID- 26874598 TI - Long-term outcomes after lobectomy for non-small cell lung cancer when unsuspected pN2 disease is found: A National Cancer Data Base analysis. AB - OBJECTIVE: There are few studies evaluating whether to proceed with planned resection when a patient with non-small cell lung cancer (NSCLC) unexpectedly is found to have N2 disease at the time of thoracoscopy or thoracotomy. To help guide management of this clinical scenario, we evaluated outcomes for patients who were upstaged to pN2 after lobectomy without induction therapy using the National Cancer Data Base (NCDB). METHODS: Survival of NSCLC patients treated with lobectomy for clinically unsuspected mediastinal nodal disease (cT1-cT3 cN0 cN1, pN2 disease) from 1998-2006 in the NCDB was compared with "suspected" N2 disease patients (cT1-cT3 cN2) who were treated with chemotherapy with or without radiation followed by lobectomy, using matched analysis based on propensity scores. RESULTS: Unsuspected pN2 disease was found in 4.4% of patients (2047 out of 46,691) who underwent lobectomy as primary therapy for cT1-cT3 cN0-cN1 NSCLC. The 5-year survival was 42%, 36%, 21%, and 28% for patients who underwent adjuvant chemotherapy (n = 385), chemoradiation (n = 504), radiation (n = 300), and no adjuvant therapy (n = 858), respectively. Five-year survival of the entire unsuspected pN2 cohort was worse than survival of 2302 patients who were treated with lobectomy after induction therapy for clinical N2 disease (30% vs 40%; P < .001), although no significant difference in 5-year survival was found in a matched-analysis of 655 patients from each group (37% vs 37%; P = .95). CONCLUSIONS: This population-based analysis suggests that, in the setting of unsuspected pN2 NSCLC, proceeding with lobectomy does not appear to compromise outcomes if adjuvant chemotherapy with or without radiation therapy can be administered following surgery. PMID- 26874599 TI - Surgical team turnover and operative time: An evaluation of operating room efficiency during pulmonary resection. AB - OBJECTIVE: Health care resources are costly and should be used judiciously and efficiently. Predicting the duration of surgical procedures is key to optimizing operating room resources. Our objective was to identify factors influencing operative time, particularly surgical team turnover. METHODS: We performed a single-institution, retrospective review of lobectomy operations. Univariate and multivariate analyses were performed to evaluate the impact of different factors on surgical time (skin-to-skin) and total procedure time. Staff turnover within the nursing component of the surgical team was defined as the number of instances any nurse had to leave the operating room over the total number of nurses involved in the operation. RESULTS: A total of 235 lobectomies were performed by 5 surgeons, most commonly for lung cancer (95%). On multivariate analysis, percent forced expiratory volume in 1 second, surgical approach, and lesion size had a significant effect on surgical time. Nursing turnover was associated with a significant increase in surgical time (53.7 minutes; 95% confidence interval, 6.4 101; P = .026) and total procedure time (83.2 minutes; 95% confidence interval, 30.1-136.2; P = .002). CONCLUSIONS: Active management of surgical team turnover may be an opportunity to improve operating room efficiency when the surgical team is engaged in a major pulmonary resection. PMID- 26874600 TI - Transfusion of sex-mismatched and non-leukocyte-depleted red blood cells in cardiac surgery increases mortality. AB - OBJECTIVE: To examine the mortality risk of blood transfusions when donor information, postdonation treatment, and a wide selection of risk factors are taken into account. METHODS: A retrospective study was performed on 9907 patients who underwent coronary artery bypass grafting and/or aortic valve replacement. Several transfusion-related risk factors, including age of blood products, sex of donor, ABO group, Rh group, posttransfusion treatment, and sex matching, were included in the analysis. A wide selection of preoperative comorbidities were included as well. A Cox proportional hazards analysis was performed to determine significant risk factors. Patients were followed for a period of up to 12 years posttransfusion. RESULTS: We found an excess mortality for transfusions of sex mismatched red blood cells (RBCs) per unit transfused (hazard ratio [HR], 1.083; 95% confidence interval [CI] 1.028-1.140; P = .003). In addition, we found a significant risk during the first year for transfusing 1 to 2 units of non leukocyte-depleted RBCs (HR, 1.426; 95% CI, 1.004-2.024; P = .047). Transfusion of 1 to 2 units of leukocyte-depleted RBCs was not associated with increased risk (HR, 0.981; 95% CI, 0.866-1.110; P = not significant). The age of blood products was not associated with increased mortality. CONCLUSIONS: In this large retrospective study, transfusion of non-sex-matched RBCs was associated with increased mortality. In addition, in patients receiving small amounts of blood, leukocyte depletion of RBCs had a beneficial effect on patient survival. PMID- 26874601 TI - Adventitial inversion in the distal anastomosis in surgical treatment of acute DeBakey type I aortic dissection. PMID- 26874602 TI - The view from the other side of the table: Beginning a practice in academic thoracic surgery. PMID- 26874603 TI - Cardiothoracic surgery training in Israel: A critical look at the past, aiming for a better future. AB - Training the next generation of cardiothoracic surgeons is a global persistent challenge. Major issues, including length of training, decreasing volume of cases, shift toward high-risk, complex, and less-invasive procedures, increased specialization, and uncertainty with regard to future employment, are relevant and affect residency training programs in the United States, Europe, and other parts of the world. To produce high-quality, mature, and qualified surgeons, these challenges mandate an ongoing effort by our specialty leadership aimed at identifying creative solutions and adapting the current residency training curricula and methodology to the dynamic changes in our field. The current situation in Israel is discussed with the hope that sharing our experience might be useful and lead to adoption of some of our solutions by other countries. PMID- 26874604 TI - Arch reconstruction after a previous ascending-to-descending aortic bypass for coarctation of the aorta. PMID- 26874605 TI - Cardiothoracic surgical critical care certification: A future of distinction. AB - Cardiothoracic surgical critical care has emerged as a unique area of practice within cardiothoracic surgery. Leaders of multidisciplinary, high-performing teams are uniquely educated, trained, and skilled surgeons. Certification in this specialty by the American Board of Thoracic Surgery is a recognition of their distinction. A foundational framework is proposed toward this goal. PMID- 26874606 TI - The concept of intraoperative, "unsuspected" N2: It's suspect. PMID- 26874607 TI - Benchtop hemodynamic studies of transcatheter valves: Has the horse come after the cart? PMID- 26874608 TI - Metal resistance systems in cultivated bacteria: are they found in complex communities? AB - Metal resistance systems found in complex bacterial communities by shotgun metagenomic approaches were reviewed. For that, 6 recent studies investigating 9 metal-contaminated environments (water or sediments) were selected. Of the 22 possible metal-resistance systems, only 14 were found in complex communities. These widespread and easily detected metal-resistance systems were mainly biogenic sulfide production (dsr genes), resistance mediated in the periplasm (CopK and multicopper oxidases such as PcoA/CopA), efflux proteins (HME-RND systems, P-type ATPases, and the cation diffusion facilitator CzcD) as well as proteins used to treat oxidative damages (e.g., SodA) and down-regulation of transporters. A total of 8 metal-resistance systems were not found in the complex communities investigated. These rare systems include metal resistance by phosphatases, ureases, metallophores, outer membrane vesicles, methylation genes and cytoplasmic metal accumulation systems. In this case rarity may also be explained by a lack of knowledge on the specific genes involved and/or analytical biases. PMID- 26874609 TI - The membrane-biofilm reactor (MBfR) as a counter-diffusional biofilm process. AB - The membrane-biofilm reactor (MBfR), sometimes known as the membrane-aerated biofilm reactor (MABR), is an emerging treatment technology based on gas transferring membranes. The membranes typically supply a gaseous electron donor or acceptor substrate, such as oxygen, hydrogen, and methane. The substrate diffuses through the membrane to a biofilm naturally forming on the membrane outer surface. The complementary substrate (electron donor or acceptor) typically diffuses from the bulk liquid into the biofilm, making MBfR counter diffusional. This paper reviews the unique behavior of counter-diffusional biofilms and highlights recent research on the MBfR. Key advances include insights into the microbial community structure of MBfRs, applying the MBfR to novel contaminants, providing a better understanding of biofilm morphology and its effects on MBfR behavior, and the development of methane-based MBfR applications. These advances are likely to further the development of the MBfR for environmental applications, such as energy-efficient wastewater treatment and advanced water treatment. PMID- 26874610 TI - Fate and transport of tylosin-resistant bacteria and macrolide resistance genes in artificially drained agricultural fields receiving swine manure. AB - Application of manure from swine treated with antibiotics introduces antibiotics and antibiotic resistance genes to soil with the potential for further movement in drainage water, which may contribute to the increase in antibiotic resistance in non-agricultural settings. We compared losses of antibiotic-resistant Enterococcus and macrolide-resistance (erm and msrA) genes in water draining from plots with or without swine manure application under chisel plow and no till conditions. Concentrations of ermB, ermC and ermF were all >10(9)copies g(-1) in manure from tylosin-treated swine, and application of this manure resulted in short-term increases in the abundance of these genes in soil. Abundances of ermB, ermC and ermF in manured soil returned to levels identified in non-manured control plots by the spring following manure application. Tillage practices yielded no significant differences (p>0.10) in enterococci or erm gene concentrations in drainage water and were therefore combined for further analysis. While enterococci and tylosin-resistant enterococci concentrations in drainage water showed no effects of manure application, ermB and ermF concentrations in drainage water from manured plots were significantly higher (p<0.01) than concentrations coming from non-manured plots. ErmB and ermF were detected in 78% and 44%, respectively, of water samples draining from plots receiving manure. Although ermC had the highest concentrations of the three genes in drainage water, there was no effect of manure application on ermC abundance. MsrA was not detected in manure, soil or water. This study is the first to report significant increases in abundance of resistance genes in waters draining from agricultural land due to manure application. PMID- 26874611 TI - Photocatalytic, antimicrobial activities of biogenic silver nanoparticles and electrochemical degradation of water soluble dyes at glassy carbon/silver modified past electrode using buffer solution. AB - In the present research work a novel, nontoxic and ecofriendly procedure was developed for the green synthesis of silver nano particle (AgNPs) using Caruluma edulis (C. edulis) extract act as reductant as well as stabilizer agents. The formation of AgNPs was confirmed by UV/Vis spectroscopy. The small and spherical sizes of AgNPs were conformed from high resolution transmission electron microscopy (HRTEM) analysis and were found in the range of 2-10nm, which were highly dispersion without any aggregation. The crystalline structure of AgNPs was conformed from X-ray diffraction (XRD) analysis. For the elemental composition EDX was used and FTIR helped to determine the type of organic compounds in the extract. The potential electrochemical property of modified silver electrode was also studied. The AgNPs showed prominent antibacterial motion with MIC values of 125 MUg/mL against Bacillus subtilis and Staphylococcus aureus while 250 MUg/mL against Escherichia coli. High cell constituents' release was exhibited by B. subtilis with 2 * MIC value of silver nanoparticles. Silver nanoparticles also showed significant DPPH free radical scavenging activity. This research would have an important implication for the synthesis of more efficient antimicrobial and antioxidant agent. The AgNP modified electrode (GC/AgNPs) exhibited an excellent electro-catalytic activity toward the redox reaction of phenolic compounds. The AgNPs were evaluated for electrochemical degradation of bromothymol blue (BTB) dyes which showed a significant activity. From the strong reductive properties it is obvious that AgNPs can be used in water sanitization and converting some organic perilous in to non-hazardous materials. The AgNPs showed potential applications in the field of electro chemistry, sensor, catalyst, nano-devices and medical. PMID- 26874612 TI - Theoretical modeling of indoor radon concentration and its validation through measurements in South-East Haryana, India. AB - A three dimensional semi-empirical model deduced from the existing 1-D model has been used to predict indoor radon concentration with theoretical calculations. Since the major contributor of radon concentration in indoors originates from building materials used in construction of walls and floor which are mostly derived from soil. In this study different building materials have been analyzed for radon exhalation, diffusion length along with physical dimensions of observation area to calculate indoor radon concentration. Also calculated values have been validated by comparing with experimental measurements. The study has been carried out in the mud, brick and cement houses constructed from materials available locally in South-East region of Haryana. This region is also known for its protruding land structure consisting volcanic, felsite and granitic rocks in plane. Further, exhalation (Jw) ratio from wall and floor comparison has been plotted for each selected village dwelling to identify the high radon emanating source (building material) from the study region. All those measured factors might be useful in building construction code development and selection of material to be used in construction. PMID- 26874613 TI - Conversion from forests to pastures in the Colombian Amazon leads to differences in dead wood dynamics depending on land management practices. AB - Dead wood, composed of coarse standing and fallen woody debris (CWD), is an important carbon (C) pool in tropical forests and its accounting is needed to reduce uncertainties within the strategies to mitigate climate change by reducing deforestation and forest degradation (REDD+). To date, information on CWD stocks in tropical forests is scarce and effects of land-cover conversion and land management practices on CWD dynamics remain largely unexplored. Here we present estimates on CWD stocks in primary forests in the Colombian Amazon and their dynamics along 20 years of forest-to-pasture conversion in two sub-regions with different management practices during pasture establishment: high-grazing intensity (HG) and low-grazing intensity (LG) sub-regions. Two 20-year-old chronosequences describing the forest-to-pasture conversion were identified in both sub-regions. The line-intersect and the plot-based methods were used to estimate fallen and standing CWD stocks, respectively. Total necromass in primary forests was similar between both sub-regions (35.6 +/- 5.8 Mg ha(-1) in HG and 37.0 +/- 7.4 Mg ha(-1) in LG). An increase of ~124% in CWD stocks followed by a reduction to values close to those at the intact forests were registered after slash-and-burn practice was implemented in both sub-regions during the first two years of forest-to-pasture conversion. Implementation of machinery after using fire in HG pastures led to a reduction of 82% in CWD stocks during the second and fifth years of pasture establishment, compared to a decrease of 41% during the same period in LG where mechanization is not implemented. Finally, average necromass 20 years after forest-to-pasture conversion decreased to 3.5 +/- 1.4 Mg ha(-1) in HG and 9.3 +/- 3.5 Mg ha(-1) in LG, representing a total reduction of between 90% and 75% in each sub-region, respectively. These results highlight the importance of low-grazing intensity management practices during ranching activities in the Colombian Amazon to reduce C emissions associated with land cover change from forest to pasture. PMID- 26874614 TI - The pH-dependent release of platinum group elements (PGEs) from gasoline and diesel fuel catalysts: Implication for weathering in soils. AB - Powdered samples of new and old gasoline catalysts (Pt, Pd, Rh) and new and old diesel (Pt) catalysts were subjected to a pH-static leaching procedure (pH 2-9) coupled with thermodynamic modeling using PHREEQC-3 to verify the release and mobility of PGEs (platinum group elements). PGEs were released under acidic conditions, mostly exhibiting L-shaped leaching patterns: diesel old: 5.47, 0.005, 0.02; diesel new: 68.5, 0.23, 0.11; gasoline old: 0.1, 11.8, 4.79; gasoline new 2.6, 25.2, 35.9 in mg kg(-1) for Pt, Pd and Rh, respectively. Only the new diesel catalyst had a strikingly different leaching pattern with elevated concentrations at pH 4, probably influenced by the dissolution of the catalyst carrier and washcoat. The pH-static experiment coupled with thermodynamic modeling was found to be an effective instrument for understanding the leaching behavior of PGEs under various environmental conditions, and indicated that charged Pt and Rh species may be adsorbed on the negatively charged surface of kaolinite or Mn oxides in the soil system, whereas uncharged Pd and Rh species may remain mobile in soil solutions. PMID- 26874615 TI - Effects of tillage and poultry manure application rates on Salmonella and fecal indicator bacteria concentrations in tiles draining Des Moines Lobe soils. AB - Application of poultry manure (PM) to cropland as fertilizer is a common practice in artificially drained regions of the Upper Midwest United States. Tile-waters have the potential to contribute pathogenic bacteria to downstream waters. This 3 year study (2010-2012) was designed to evaluate the impacts of manure management and tillage practices on bacteria losses to drainage tiles under a wide range of field conditions. PM was applied annually in spring, prior to planting corn, at application rates ranging from 5 to 40 kg/ha to achieve target rates of 112 and 224 kg/ha nitrogen (PM1 and PM2). Control plots received no manure (PM0). Each treatment was replicated on three chisel-plowed (CP) plots and one no-till (NT) plot. Tile-water grab samples were collected weekly when tiles were flowing beginning 30 days before manure application to 100 days post application, and additional grab samples were obtained to target the full spectrum of flow conditions. Manure and tile-water samples were analyzed for the pathogen, Salmonella spp. (SALM), and fecal indicator bacteria (FIB), Escherichia coli (EC), and enterococci (ENT). All three bacterial genera were detected more frequently, and at significantly higher concentrations, in tile-waters draining NT plots compared to CP plots. Transport of bacteria to NT tiles was most likely facilitated by macropores, which were significantly more numerous above tiles in NT plots in 2012 as determined by smoke-testing. While post-manure samples contained higher concentrations of bacteria than pre-manure samples, significant differences were not seen between low (PM1) and high (PM2) rates of PM application. The highest concentrations were observed under the NT PM2 plot in 2010 (6.6 * 10(3) cfu/100 mL EC, 6.6 * 10(5) cfu/100 mL ENT, and 2.8 * 10(3) cfu/100 mL SALM). Individual and 30-day geometric mean ENT concentrations correlated more strongly to SALM than EC; however, SALM were present in samples with little or no FIB. PMID- 26874616 TI - Assessment of groundwater vulnerability to nitrates from agricultural sources using a GIS-compatible logic multicriteria model. AB - In the present study an overlay method to assess groundwater vulnerability is proposed. This new method based on multicriteria decision analysis (MCDA) was developed and validated using an appropriate case study in Aragon area (NE Spain). The Vulnerability Index to Nitrates from Agricultural Sources (VINAS) incorporates a novel Logic Scoring of Preferences (LSP) approach, and it has been developed using public geographic information from the European Union. VINAS-LSP identifies areas with five categories of vulnerability, taking into account the hydrogeological and environmental characteristics of the territory as a whole. The resulting LSP map is a regional screening tool that can provide guidance on the potential risk of nitrate pollution, as well as highlight areas where specific research and farming planning policies are required. PMID- 26874617 TI - TCR clonotypes: molecular determinants of T-cell efficacy against HIV. AB - Because of the enormous complexity and breadth of the overall HIV-specific CD8(+) T-cell response, invaluable information regarding important aspects of T-cell efficacy against HIV can be sourced from studies performed on individual clonotypes. Data gathered from ex vivo and in vitro analyses of T-cell responses and viral evolution bring us one step closer towards deciphering the correlates of protection against HIV. HIV-responsive CD8(+) T-cell populations are characterized by specific clonotypic immunodominance patterns and public TCRs. The TCR endows T-cells with two key features, important for the effective control of HIV: avidity and crossreactivity. While TCR avidity is a major determinant of CD8(+) T-cell functional efficacy against the virus, crossreactivity towards wildtype and mutant viral epitopes is crucial for adaptation to HIV evolution. The properties of CD4(+) T-cell responses in HIV controllers appear also to be shaped by high avidity public TCR clonotypes. The molecular nature of the TCR, together with the clonotypic composition of the HIV-specific T-cell response, emerge as major determinants of anti-viral efficacy. PMID- 26874618 TI - Applications of calcium electroporation to effective apoptosis induction in fibrosarcoma cells and stimulation of normal muscle cells. AB - The electroporation (EP) supports various types of anticancer therapies by the selective transport of cytostatics. Increase in intracellular calcium level by EP may be a new approach to fibrosarcoma treatment. Calcium is one of the most important factors of cell proliferation, differentiation and cell death (apoptosis or necrosis). Calcium level balanced by electroporation can cause different effects on normal and pathological cells. The efficiency and safety of electroporation combined with Ca(2+) ions were examined in our study. The two muscle cell lines were used: normal rat skeletal muscle cells - L6 and cancer muscle cells - Wehi-164 (fibrosarcoma). Two CaCl2 concentrations were tested: 0.5 mM and 5 mM combined with EP parameters: 1000 V/cm, 1200 V/cm, and 1500 V/cm. The results show that EP supported by Ca(2+) is cytotoxic for Wehi-164 cells and simultaneously safe for normal muscle cells. The main type of cell death - apoptosis - was confirmed by Tunnel and Annexin V/PI assay. Additionally, sPLA2 pro-tumorigenic influence was proved by immunocytochemistry. Moreover, EP with 0.5 mM of Ca(2+) slightly stimulates the normal muscle cells - L6 to increase proliferation. PMID- 26874620 TI - The elusive global burden of dengue. PMID- 26874619 TI - The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. AB - BACKGROUND: Dengue is the most common arbovirus infection globally, but its burden is poorly quantified. We estimated dengue mortality, incidence, and burden for the Global Burden of Disease Study 2013. METHODS: We modelled mortality from vital registration, verbal autopsy, and surveillance data using the Cause of Death Ensemble Modelling tool. We modelled incidence from officially reported cases, and adjusted our raw estimates for under-reporting based on published estimates of expansion factors. In total, we had 1780 country-years of mortality data from 130 countries, 1636 country-years of dengue case reports from 76 countries, and expansion factor estimates for 14 countries. FINDINGS: We estimated an average of 9221 dengue deaths per year between 1990 and 2013, increasing from a low of 8277 (95% uncertainty estimate 5353-10 649) in 1992, to a peak of 11 302 (6790-13 722) in 2010. This yielded a total of 576 900 (330 000 701 200) years of life lost to premature mortality attributable to dengue in 2013. The incidence of dengue increased greatly between 1990 and 2013, with the number of cases more than doubling every decade, from 8.3 million (3.3 million 17.2 million) apparent cases in 1990, to 58.4 million (23.6 million-121.9 million) apparent cases in 2013. When accounting for disability from moderate and severe acute dengue, and post-dengue chronic fatigue, 566 000 (186 000-1 415 000) years lived with disability were attributable to dengue in 2013. Considering fatal and non-fatal outcomes together, dengue was responsible for 1.14 million (0.73 million-1.98 million) disability-adjusted life-years in 2013. INTERPRETATION: Although lower than other estimates, our results offer more evidence that the true symptomatic incidence of dengue probably falls within the commonly cited range of 50 million to 100 million cases per year. Our mortality estimates are lower than those presented elsewhere and should be considered in light of the totality of evidence suggesting that dengue mortality might, in fact, be substantially higher. FUNDING: Bill & Melinda Gates Foundation. PMID- 26874621 TI - Reference gene selection for quantitative real-time PCR in Solanum lycopersicum L. inoculated with the mycorrhizal fungus Rhizophagus irregularis. AB - The gene expression stability of candidate reference genes in the roots and leaves of Solanum lycopersicum inoculated with arbuscular mycorrhizal fungi was investigated. Eight candidate reference genes including elongation factor 1 alpha (EF1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), protein phosphatase 2A (PP2Acs), ribosomal protein L2 (RPL2), beta-tubulin (TUB), ubiquitin (UBI) and actin (ACT) were selected, and their expression stability was assessed to determine the most stable internal reference for quantitative PCR normalization in S. lycopersicum inoculated with the arbuscular mycorrhizal fungus Rhizophagus irregularis. The stability of each gene was analysed in leaves and roots together and separated using the geNorm and NormFinder algorithms. Differences were detected between leaves and roots, varying among the best-ranked genes depending on the algorithm used and the tissue analysed. PGK, TUB and EF1 genes showed higher stability in roots, while EF1 and UBI had higher stability in leaves. Statistical algorithms indicated that the GAPDH gene was the least stable under the experimental conditions assayed. Then, we analysed the expression levels of the LePT4 gene, a phosphate transporter whose expression is induced by fungal colonization in host plant roots. No differences were observed when the most stable genes were used as reference genes. However, when GAPDH was used as the reference gene, we observed an overestimation of LePT4 expression. In summary, our results revealed that candidate reference genes present variable stability in S. lycopersicum arbuscular mycorrhizal symbiosis depending on the algorithm and tissue analysed. Thus, reference gene selection is an important issue for obtaining reliable results in gene expression quantification. PMID- 26874622 TI - Volatiles released by endophytic Pseudomonas fluorescens promoting the growth and volatile oil accumulation in Atractylodes lancea. AB - Atractylodes lancea is a well-known, but endangered, Chinese medicinal plant whose volatile oils are its main active components. As the volatile oil content in cultivated A. lancea is much lower than that in the wild herb, the application of microbes or related elicitors to promote growth and volatile oil accumulation in the cultivated herb is an important area of research. This study demonstrates that the endophytic bacterium Pseudomonas fluorescens ALEB7B isolated from the geo-authentic A. lancea can release several nitrogenous volatiles, such as formamide and N,N-dimethyl-formamide, which significantly promote the growth of non-infected A. lancea. Moreover, the main bacterial volatile benzaldehyde significantly promotes volatile oil accumulation in non-infected A. lancea via activating plant defense responses. Notably, the bacterial nitrogenous volatiles cannot be detected in the A. lancea - Pseudomonas fluorescens symbiont while the benzaldehyde can be detected, indicating the nitrogenous volatiles or their precursors may have been consumed by the host plant. This study firstly demonstrates that the interaction between plant and endophytic bacterium is not limited to the commonly known physical contact, extending the ecological functions of endophyte in the phytosphere and deepening the understandings about the symbiotic interaction. PMID- 26874623 TI - Changes of paralytic shellfish toxins in gills and digestive glands of the cockle Cerastoderma edule under post-bloom natural conditions. AB - Concentrations of the paralytic shellfish toxins C1+2, C3+4, GTX5, GTX6, dcGTX2+3, dcSTX, dcNEO, GTX2+3, GTX1+4, STX and NEO were determined by LC-FLD in composite samples of digestive glands and gills of Cerastoderma edule cockle. The specimens were sampled in Aveiro lagoon, Portugal, under natural depuration conditions (days 0, 8, 12, 14, 19, 21 and 25) after exposure to a bloom of Gymnodinium catenatum. Individual paralytic shellfish toxins indicated different pathways of elimination and biotransformation in digestive gland and gills. Toxin concentrations in gills were lower than in digestive gland. Most of the quantified toxins in digestive gland decreased during the 25 days of observation according to negative exponential curves, and only GTX5, GTX6 and NEO showed slight irregularities with time. Concentrations of C1+2, C3+4 and dcGTX2+3 in gills decreased progressively, however GTX5, GTX6 and dcSTX showed pronounced increases. Higher concentrations of those toxins in days 8 and 12 in comparison to the initial value (day 0) indicate conversion of other toxins into GTX5, GTX6 and dcSTX during those periods. It appears that inter-conversion of toxins occurs as G. catenatum cells are retained in gills before being transferred to other compartments. PMID- 26874624 TI - Residues, spatial distribution and risk assessment of DDTs and HCHs in agricultural soil and crops from the Tibetan Plateau. AB - Due to its high elevation and cold temperature, the Tibetan Plateau (TP) is regarded as the "Third Pole". Different from other polar regions, which are truly remote, the TP has a small population and a few agricultural activities. In this study, agricultural soil and crop samples (including highland barley and rape) were collected in the main farmland of the TP to obtain the contamination levels of dichlorodiphenyltrichloroethane (DDT) and hexachlorocyclohexane (HCH) in the Tibetan agricultural system as well as the relevant human exposure risks. The average concentrations of DDTs and HCHs in the agricultural soil, highland barley and rape were 1.36, 0.661, 1.03 ng/g dw and 0.349, 0.0364, 0.0225 ng/g dw, respectively. In the agricultural soil, DDTs and HCHs metabolism (DDE, DDD and beta-HCH) were abundant, which indicated a "historical" source, whereas crops contained a similar composition ((DDE + DDD)/DDT, alpha/beta-HCH and alpha/gamma HCH) to that of wild plants, suggesting that the DDTs and HCHs in crops are likely from long range atmospheric transport. The human health risks via non dietary and dietary to DDTs and HCHs in the farmland were assessed. All of the hazard index (HI) values of DDTs and HCHs for non-carcinogenic risks were <1, and most of the cancer risk values were <10(-6), suggesting that DDTs and HCHs in the farmland will not pose non-carcinogenic risks and will pose only very low cancer risks to the Tibetan residents. PMID- 26874625 TI - Arsenic-induced plant growth of arsenic-hyperaccumulator Pteris vittata: Impact of arsenic and phosphate rock. AB - Phosphate rock (PR) has been shown to promote plant growth and arsenic (As) uptake by As-hyperaccumulator Pteris vittata (PV). However, little is known about its behaviors in agricultural soils. In this study, impact of 50 mg kg(-1) As and/or 1.5% PR amendment on plant As accumulation and growth was investigated by growing PV for 90 d in three agricultural soils. While As amendment significantly increased plant As uptake and substantially promoted PV growth, the opposite was observed with PR amendment. Arsenic amendment increased plant frond As from 16.9 265 to 961-6017 mg kg(-1),whereas PR amendment lowered frond As to 10.2-216 mg kg(-1). The As-induced plant growth stimulation was 69-71%. While PR amendment increased plant Ca and P uptake, As amendment showed opposite results. The PV biomass was highly correlated with plant As at r = 0.82, but with weak correlations with plant Ca or P at r < 0.30. This study confirmed that 1) As significantly promoted PV growth, probably independent of Ca or P uptake, 2) PR amendment didn't enhance plant growth or As uptake by PV in agricultural soils with adequate available P, and 3) PV effluxed arsenite (AsIII) growing in agricultural soils. PMID- 26874627 TI - What is the rationale for early intervention after osteoporotic fractures to avoid recurrent fractures? PMID- 26874626 TI - Biodegradation of phenolic compounds by Basidiomycota and its phenol oxidases: A review. AB - The phylum Basidiomycota include organisms with enormous bioremediation potential. A variety of processes were proposed at the lab scale for using these fungi and their phenol oxidases in the degradation of phenolics. Here we present a survey of this topic using literature published mostly over the last 10 years. First, the sources of the enzymes are summarized. The laccase and tyrosinase were mainly from Trametes versicolor and Agaricus bisporus, respectively. Recently, however, new promising wild-type producers of the enzymes have emerged and a number of recombinant strains were also constructed, based mainly on yeasts or Aspergillus strains as hosts. The next part of the study summarizes the enzyme and whole-cell applications for the degradation of phenols, polyphenols, cresols, alkylphenols, naphthols, bisphenols and halogenated (bis)phenols in model mixtures or real wastewaters from the food, paper and coal industries, or municipal and hospital sewage. The enzymes were applied as free (crude or purified) enzymes or as enzymes immobilized in various supports or CLEAs, and optionally recycled or used in continuous mode. Alternatively, growing cultures or harvested mycelia were used instead. The products, which were characterized as quinones and their polymers in some cases, could be eliminated by filtration, flocculation or adsorption onto chitosan. The purity of a treated wastewater was monitored using a sensitive aquatic organism. It is concluded that low-cost sources of these enzymes should be searched for and the benefits of enzymatic, biological and physico-chemical methods could be combined to make the processes fit for industrial use. PMID- 26874628 TI - Sonoelastographic evaluation of the distal femoral cartilage in patients with anterior cruciate ligament reconstruction. AB - OBJECTIVES: This study aims to evaluate sonoelastographic properties of the distal femoral cartilage in patients with anterior cruciate ligament (ACL) reconstruction. PATIENTS AND METHODS: Demographic characteristics and operative data of 28 patients (27 males, 1 female; mean age 31.7+/-7.1 years; range 22 to 48 years) with unilateral ACL reconstruction were evaluated. Reconstruction was performed with patellar tendon graft in 22 patients (78.6%) and hamstring tendon graft in six patients (21.4%). Lysholm knee score was used for functional evaluation and chair stand test was used for lower extremity strength. Medial, intercondylar, and lateral distal femoral cartilage thicknesses of operated knees and healthy knees were measured with B-mode ultrasound, while strain ratios were measured with real time sonoelastography. RESULTS: Postoperative mean follow-up duration was 20.4+/-9.8 months. Mean Lysholm knee and patient satisfaction scores were 88.0+/-8.5 and 8.2+/-1.8, respectively. Cartilage thicknesses were similar between operated and healthy knees (all p>0.05). Sonoelastographic strain ratio of medial distal femoral cartilage in operated knees was significantly higher (softer cartilage) (p=0.026). There was a negative correlation between strain ratio difference of medial cartilage of operated knees and lower extremity muscle strength (p=0.009, r= -0.487). CONCLUSION: While there was no difference for cartilage thickness between operated and healthy knees in B-mode ultrasound evaluation, detection of sonoelastographic strain ratio changes in medial distal femoral cartilage on the operated sides may indicate early structural changes following ACL reconstruction. Further studies are required to highlight the clinical effects of this relationship between the changes in cartilage structure and sonoelastography features. PMID- 26874629 TI - Histological and biomechanical effects of zoledronate on fracture healing in an osteoporotic rat tibia model. AB - OBJECTIVES: This study aims to investigate the effects of zoledronate therapy on histological and biomechanical properties of bone healing via a fracture model generated on osteoporotic rat tibiae. MATERIALS AND METHODS: Ovariectomized 40 Wistar-Dawley female rats weighing 300 g to 350 g were used in the study. After one week, 2 IU/g heparin injection was started subcutaneously. After four weeks of daily injections, osteoporosis was ensued proven with bone mineral density measurements. Osteoporotic rats were separated into four equal groups randomly as group A (control), group B (calcium and vitamin D), group C (0.1 mg/kg subcutaneous zoledronic acid), and group D (calcium and vitamin D / 0.1 mg/kg subcutaneous zoledronic acid). Six weeks later, all rats were sacrificed, their tibiae were resected, and histopathologic and biomechanical studies were performed. RESULTS: Group C (30.2+/-1 Nm) and group D (33.3+/-3 Nm) had significantly higher peak torque values than group A (21.6+/-6 Nm) and group B (23.6+/-4 Nm) (p=0.007 and p=0.005, respectively). Group C (1.8) and group D (2.0) had higher stiffness values than group A (1.4) and group B (1.7); however, the difference was not statistically significant (p>0.05 for all). CONCLUSION: According to histopathological and biomechanical test results, single dose zoledronic acid treatment improves fracture healing in an osteoporotic rat fracture model. Orally administered daily calcium and vitamin D treatment had no effect on fracture healing. There was no additional improvement in fracture healing when calcium and vitamin D treatment was added to zoledronic acid treatment. Positive effects of zoledronic acid treatment on osteoporotic fracture healing and callus quality should be shown by future clinical studies. PMID- 26874630 TI - The effect of teicoplanin on fracture healing: an experimental study. AB - OBJECTIVES: This study aims to investigate the effect of teicoplanin on fracture healing stereologically and histopatologically. MATERIALS AND METHODS: Twenty male Wistar albino rats were separated into two as the study (teicoplanin) and control groups. After intramedullary fixation of the right tibia of all the rats with 0.5 mm Kirschner wire under general anesthesia, standard closed shaft fractures were created using fracture formation apparatus. Teicoplanin (10 mg/kg) and saline were administered intraperitoneally to the study and control groups, respectively. Control radiographs were taken at the end of the procedure and the rats were sacrificed after 28 days. New bone and connective tissue volumes were calculated on obtained tissue samples using unbiased stereological and histopathological techniques. RESULTS: It was observed that teicoplanin increased the formation of bone, vascularization, and connective tissue. There was a statistically significant difference between the two groups in respect of bone and vascular total volume (p<0.05). Although an increase was observed in connective tissue total volume, no statistically significant difference was detected between the two groups (p>0.05). CONCLUSION: In addition to its antibacterial effect, teicoplanin may increase new bone formation; thus, it may be used safely in the treatment of bone defects accompanied with infection. PMID- 26874631 TI - Are pedicular screws and lateral hook screws more resistant against pullout than conventional spinal hooks and screws in terminal vertebral segment fixation? AB - OBJECTIVES: This study aims to biomechanically evaluate and compare four well known types of terminal spinal constructs to a novel construct composed of a transpedicular screw with a lateral hook screw in terms of axial pullout strength in terminal vertebral segment fixation. MATERIALS AND METHODS: Forty fresh-frozen lamb spines were divided into five groups with eight spines each. To stabilize the transverse process, a pedicular screw alone was used in group 1, a sublaminar hook alone was used in group 2, a sublaminar hook and a pedicular screw were used in group 3, claw hook alone was used in group 4, and a pedicular screw with a lateral hook screw was used in group 5. Biomechanical tests were performed using an axial compression testing machine and two noncontact camera systems. RESULTS: The mean pullout strength value was 927 N for group 1, 626 N for group 2, 988 N for group 3, 972 N for group 4, and 1194 N for group 5. Pullout strength values were statistically significantly higher in groups 3 and 4 compared to groups 1 and 2. There was no statistically significant difference between groups 3 and 4. Pullout strength value of group 5 was statistically significantly higher than the other groups. CONCLUSION: Pedicular screw with a lateral hook screw had the highest fixation value. Lateral hook screw may assist to prevent pullout in patients with pullout risk and hyperkyphosis and after hyperkyphosis surgery. Further prospective clinical studies are needed to show the benefit of such a construct in reducing the risk of distal instrumentation pullout. PMID- 26874632 TI - Should we continue to administer blind shoulder injections? AB - OBJECTIVES: This study aims to investigate the accuracy and effectiveness of blind and fluoroscopic-guided intra-articular shoulder injections in patients with shoulder pain. PATIENTS AND METHODS: The study included 17 patients (6 males, 11 females; mean age 52.6+/-9.9 years; range 36 to 66 years) with shoulder pain more than three months. First intra-articular joint injections were performed with anterior approach blindly. Following the injection and after confirming that the needle tip was intra-articular with fluoroscopy and contrast distribution, the procedure was completed using 3 mL of local anesthetic (prilocaine and bupivacaine) and 1 mL of steroid (40 mg methylprednisolone). When the contrast distribution was observed to be extra-articular at the first administration, a second injection was continued under fluoroscopy guidance. All of the injections were intra-articular with the continuation of the procedure. Pain intensity was measured with visual analog scale (VAS). RESULTS: According to the contrast distribution viewed with fluoroscopy, first blind injections were intra-articular in 11 of the 17 shoulders (64.7%). Mean of initial VAS score was 7.11. Improved pain was observed in the clinical follow-ups at the first hour (mean VAS: 2.35), third day (mean VAS: 2.64), and at the end of the first month (mean VAS: 2.23). The mean durations for blind and fluoroscopic-guided procedures excluding patients' preparation time were 0.8 minutes and 4.2 minutes, respectively. CONCLUSION: Although blind intra-articular shoulder injections are inexpensive and easily applicable, injections should be performed under fluoroscopy or another guide to ensure that the needle is intra-articular, not peri-articular. PMID- 26874633 TI - [Preferences of surgeons in total knee and hip arthroplasty, and operating room facilities in Turkey: a survey]. AB - OBJECTIVES: This study aims to determine the pre- and postoperative approaches of orthopedic surgeons and operative room environment facilities in total knee arthroplasty (TKA) and total hip arthroplasty (THA) in Turkey. MATERIALS AND METHODS: Data for this study were collected through a questionnaire completed by 234 physicians randomly identified from the database of Turkish Society of Orthopedics and Traumatology. The questionnaire comprised 19 questions investigating the operative room environment, demographic characteristics of surgeons, laboratory and radiologic analyses required by surgeons in pre- and postoperative patient evaluation, and management of postoperative complications. RESULTS: In Turkey, 48% of the operating rooms where TKA and THA are performed lack laminar airflow, while 35% lack HEPA filters. Only 20.5% of surgeons continue antibiotic prophylaxis for postoperative 24 hours. Low molecular weight heparins are the most preferred anticoagulant (86%) for thromboembolism prophylaxis. While all surgeons perform primary TKA or THA, only 63.7% perform revision TKA or THA. Of the surgeons, 84.6% do not recommended antibiotic prophylaxis before dental or urologic procedures in patients who were performed TKA or THA. CONCLUSION: In Turkey, although consensus has been built on many issues regarding TKA and THA, different approaches are adopted based on academic position, duration of specialty, and employer institution. PMID- 26874634 TI - Humeral shaft fractures and radial nerve palsy: early exploration findings. AB - OBJECTIVES: This study aims to present the results of early nerve explorations in cases with radial nerve palsy associated with humeral shaft fracture and to investigate in which cases early nerve explorations may be beneficial. PATIENTS AND METHODS: Twenty-four patients (17 males, 7 females; mean age 36 years; range 18 to 72 years) with complete sensory and motor radial nerve damage associated with humeral shaft fracture were retrospectively analyzed. The patients with high energy trauma and the ones who had spiral and segmental fractures with low energy traumas were included in the study. Early nerve exploration was performed in all patients within an average of 4.8 days (range 1 to 20 days) after fracture development. Electrophysiological assessments were performed in cases with no neurological recovery until 12th week. RESULTS: Spiral fractures of the humerus shaft observed in 14 (58.3%) of the 24 operated patients were the most common fracture type, followed by transverse fracture in four patients (16.6%) and comminuted fracture in two patients (8.3%). As a result of the exploration, we observed nerve compression between the fracture fragments in seven patients (29.1%); a majority of these patients (n=6) had spiral fractures of humerus and one patient had comminuted fracture. One patient with a spiral type fracture had nerve transection. Radial nerve function recovered in most of the patients (95.8%). Average duration for fracture union was 6.7+/-3.8 months (range 3 to 18 months). CONCLUSION: Spiral fractures of humerus, particularly with wedge fragment, may be a candidate for early surgical exploration. Early exploration may be beneficial in terms of early identification of neural injury in patients with radial nerve dysfunction associated with spiral and comminuted humerus fracture. PMID- 26874635 TI - Aggressive hemangioma of the spine in a pregnant female: a case report and literature review. AB - Type and timing of treatment for symptomatic hemangiomas in pregnant females are challenging due to fetus survival and conflicts in neurological recovery. In this article, we report a 40-year-old female patient at pregnancy week 23 with a complicated hemangioma at T1 level. Physical examination revealed an incomplete spastic paraplegia. Patient did not accept any surgery due to child's death risk. Patient was started corticoid treatment and no more weight bearing was allowed. At the 28th week of pregnancy, the patient underwent cesarean section immediately followed by selective arterial embolization, decompression, fixation, and radiotherapy. At two-year follow-up, the patient was pain free, without any signs of local recurrence and with complete neurological recovery. A multidisciplinary approach is mandatory to save the life of the fetus without damaging the spinal cord functions of the mother. PMID- 26874636 TI - One patient, one bone, and two different tumoral lesions. AB - In this article, we report a 67-year-old female patient who has two different tumoral lesions located in left humerus with clinical and radiological findings. Previously, the patient was diagnosed as impingement syndrome in shoulder, but, tumoral lesions were detected on the radiograms incidentally during evaluation. PMID- 26874637 TI - Atypical femoral fracture following zoledronic acid treatment. AB - A 68-year-old female patient admitted to our clinic with right anterior thigh pain ongoing for six months and which increased in last two months. The patient had no trauma history. The patient had been followed-up for 15 years because of osteoporosis and administrated alendronate and ibandronate treatment for 10 years. Patient had three shots of zoledronate once a year during the last three years. Her pain was increasing when she was walking. Physical examination revealed pain in her right thigh. Radiogram showed thickened lateral cortex of the subtrochanteric area. Magnetic resonance imaging also showed thickening and edema of the same area. These images were correlated with atypical fracture in right femoral subthrochanteric zone. Dual energy X-ray absorptiometry revealed that T score was -3.3 in lumbar region and -2.5 in femoral neck. Zoledronate treatment was ended. Prophylactic surgical fixation was performed with titanium elastic nails. PMID- 26874638 TI - An extraordinary mechanism causing intraoperative migration of the Kirschner wire. AB - Migration of Kirschner wires (K-wires) postoperatively and with use of cannulated implants intraoperatively is a well-known complication. In this article, we present an extraordinary mechanism causing intraoperative migration of a K-wire. A K-wire which was used for temporary fixation of fracture fragments migrated forwardly due to its contact with the drill bit while drilling a hole for a screw. The interaction between the K-wire and the drill bit simulated a gear wheel effect and thus the rotating K-wire advanced. Although no complications occurred in this case, we believe that the mentioned mechanism may be of importance particularly in osteoporotic patients and may cause damage to vital structures. PMID- 26874640 TI - Survey of food-grade silica dioxide nanomaterial occurrence, characterization, human gut impacts and fate across its lifecycle. AB - There is increasing recognition of the importance of transformations in nanomaterials across their lifecycle, yet few quantitative examples exist. We examined food-grade silicon dioxide (SiO2) nanomaterials from its source (bulk material providers), occurrence in food products, impacts on human gastrointestinal tract during consumption, and fate at wastewater treatment plants. Based upon XRD, XPS and TEM analysis, pure SiO2 present in multiple food grade stock SiO2 exhibited consistent morphologies as agglomerates, ranging in size from below 100nm to >500nm, with all primary particle size in the range of 9 26nm and were most likely amorphous SiO2 based upon high resolution TEM. Ten of 14 targeted foods purchased in the USA contained SiO2 of the same morphology and size as the pristine bulk food-grade SiO2, at levels of 2 to 200mg Si per serving size. A dissolution study of pristine SiO2 showed up to 7% of the dissolution of the silica, but the un-dissolved SiO2 maintained the same morphology as the pristine SiO2. Across a realistic exposure range, pristine SiO2 exhibited adverse dose-response relationships on a cell model (microvilli) of the human gastro intestinal tract, association onto microvilli and evidence that SiO2 lead to production of reactive oxygen species (ROS). We also observed accumulation of amorphous nano-SiO2 on bioflocs in tests using lab-cultured activated sludge and sewage sludges from a full-scale wastewater treatment plant (WWTP). Nano-scale SiO2 of the same size and morphology as pristine food-grade SiO2 was observed in raw sewage at a WWTP, but we identified non-agglomerated individual SiO2 particles with an average diameter of 21.5+/-4.7nm in treated effluent from the WWTP. This study demonstrates an approach to track nanomaterials from source-to sink and establishes a baseline occurrence of nano-scale SiO2 in foods and WWTPs. PMID- 26874639 TI - Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV Induced Infectious Mononucleosis in Patients with Atopic Predispositions. AB - BACKGROUND: Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus (EBV) infection. In adults, the symptoms can often be severe and prolonged, sometimes causing serious complications. Analgesic or antipyretic drugs are normally used to relieve the symptoms. However, there is no causal treatment for the disease. CASE REPORT: Two cases of adult patients with atopic predispositions developed nocturnal fever, general fatigue, pharyngitis and lymphadenopathy after an exacerbation of atopic symptoms or those of allergic rhinitis. Due to the positive results for EBV viral capsid antigen (VCA) IgM and negative results for EBV nuclear antigen (EBNA) IgG, diagnoses of infectious mononucleosis induced by EBV were made in both cases. Although oral antibiotics or acetaminophen alone did not improve the deteriorating symptoms, including fever, headache and general fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs), such as tiaramide or loxoprofen, completely improved the symptoms quickly after the initiation. CONCLUSIONS: In these cases, given the atopic predispositions of the patients, an enhanced immunological response was likely to be mainly responsible for the pathogenesis of the symptoms. In such cases, NSAIDs, that are known to reduce the activity of EBV, may dramatically improve the deteriorating symptoms quickly after the initiation. In the present cases, the immunosuppressive property of these drugs was considered to suppress the activity of lymphocytes and thus provide the rapid and persistent remission of the disease. PMID- 26874641 TI - Direct toxicity assessment - Methods, evaluation, interpretation. AB - Direct toxicity assessment (DTA) results provide the scale of the actual adverse effect of contaminated environmental samples. DTA results are used in environmental risk management of contaminated water, soil and waste, without explicitly translating the results into chemical concentration. The end points are the same as in environmental toxicology in general, i.e. inhibition rate, decrease in the growth rate or in yield and the 'no effect' or the 'lowest effect' measurement points of the sample dilution-response curve. The measurement unit cannot be a concentration, since the contaminants and their content in the sample is unknown. Thus toxicity is expressed as the sample proportion causing a certain scale of inhibition or no inhibition. Another option for characterizing the scale of toxicity of an environmental sample is equivalencing. Toxicity equivalencing represents an interpretation tool which enables toxicity of unknown mixtures of chemicals be converted into the concentration of an equivalently toxic reference substance. Toxicity equivalencing, (i.e. expressing the toxicity of unknown contaminants as the concentration of the reference) makes DTA results better understandable for non-ecotoxicologists and other professionals educated and thinking based on the chemical model. This paper describes and discusses the role, the principles, the methodology and the interpretation of direct toxicity assessment (DTA) with the aim to contribute to the understanding of the necessity to integrate DTA results into environmental management of contaminated soil and water. The paper also introduces the benefits of the toxicity equivalency method. The use of DTA is illustrated through two case studies. The first case study focuses on DTA of treated wastewater with the aim to characterize the treatment efficacy of a biological wastewater treatment plant by frequent bioassaying. The second case study applied DTA to investigate the cover layers of two bauxite residue (red mud) reservoirs. Based on the DTA results the necessary toxicity attenuation rate of the cover layers was estimated. PMID- 26874642 TI - A Rare Case of Type III Dens Invaginatus in a Mandibular Second Premolar and Its Nonsurgical Endodontic Management by Using Cone-beam Computed Tomography: A Case Report. AB - Invaginated teeth present technical difficulties in clinical management because of their abnormal anatomic configuration. Endodontic clinical management of type III dens invaginatus can be greatly enhanced by newer techniques and materials such as cone-beam computed tomography (CBCT), mineral trioxide aggregate, and platelet-rich fibrin. This case report presents a 13-year-old male patient with type III dens invaginatus (DI) in left mandibular second premolar with history of recurrent swelling. Pulp testing revealed no response with the tooth. Dens invaginatus type III with an immature apex and periapical lesion was seen on radiograph. The case was diagnosed as Oehlers type III DI with pulp necrosis and chronic apical abscess. The treatment was planned and performed by using CBCT imaging. CBCT was performed to see the canal anatomy and to know the size of periapical lesion. Root canal treatment was completed in 2 visits. Calcium hydroxide dressing was placed in the first visit. In the second visit MTA was used for apexification in the main canal, and warm vertical compaction technique with gutta-percha was used in the invaginated canal. At the 2-year reevaluation, the patient was asymptomatic, and his tooth had remained functional since the treatment was completed. Radiographic assessment of the tooth showed significant osseous healing of the preoperative lesion. Three-dimensional imaging is a valuable tool for endodontic management of teeth with complex internal anatomy. PMID- 26874644 TI - The power of advocacy. PMID- 26874643 TI - Biodentine Reduces Tumor Necrosis Factor Alpha-induced TRPA1 Expression in Odontoblastlike Cells. AB - INTRODUCTION: The transient receptor potential (TRP) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with TRPA1 playing a central role in nociception and neurogenic inflammation. The functionality of TRP channels has been shown to be modulated by inflammatory cytokines. The aim of this study was to investigate the effect of inflammation on odontoblast TRPA1 expression and to determine the effect of Biodentine (Septodent, Paris, France) on inflammatory-induced TRPA1 expression. METHODS: Immunohistochemistry was used to study TRPA1 expression in pulp tissue from healthy and carious human teeth. Pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/L beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, Western blotting, calcium imaging, and patch clamp studies. RESULTS: Immunofluorescent staining revealed TRPA1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. TRPA1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of Biodentine. The functionality of the TRPA1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced TRPA1 responses after Biodentine treatment. CONCLUSIONS: In conclusion, this study showed TRPA1 to be modulated by caries-induced inflammation and that Biodentine reduced TRPA1 expression and functional responses. PMID- 26874645 TI - Tolvaptan and Neurocognitive Function in Mild to Moderate Chronic Hyponatremia: A Randomized Trial (INSIGHT). AB - BACKGROUND: This trial assessed the effect of tolvaptan on cognition, gait, and postural stability in adult patients with mild to moderate asymptomatic hyponatremia. STUDY DESIGN: Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group pilot study. SETTING & PARTICIPANTS: 57 men and women 50 years or older with chronic asymptomatic euvolemic or hypervolemic hyponatremia (serum sodium concentration >120-<135 mEq/L) at 16 sites. INTERVENTION: Patients were randomly assigned 1:1 to receive tolvaptan or matching placebo beginning at a dose of 15mg/d, with titration to 30 or 60mg/d based on change in serum sodium concentration and tolerance. OUTCOMES: Primary: change from baseline in the neurocognitive composite score of speed domains. Secondary: changes from baseline in individual neurocognitive domain scores, overall neurocognitive composite score, gait and postural stability test results, and serum sodium concentrations. RESULTS: Mean serum sodium concentration increased from 129 to 136 mEq/L in the tolvaptan group and from 130 to 132 mEq/L in the placebo group (P<0.001). There was no difference in overall neurocognitive composite scores of speed domains between groups, except for the psychomotor speed domain, which was statistically improved following hyponatremia correction with tolvaptan (treatment effect, 0.27; 95% CI, 0.04-0.51; P=0.03). LIMITATIONS: There were some imbalances between treatment groups in baseline neurocognitive function scores and some baseline test results were near normal, leaving little opportunity for improvement. Formal sample size calculations were not performed because this was a pilot study. The study population was small (n=57) and treatment was of short duration (3 weeks). The primary end point of the study was not significant; thus, subgroup analyses are subject to errors of multiplicity and should be regarded as hypothesis generating. CONCLUSIONS: Tolvaptan was effective in reversing chronic hyponatremia, and this correlated with improvements in results of a variety of neurocognition tests, particularly rapid motor movements, which tended to reverse following return to a low baseline serum sodium concentration after treatment withdrawal. PMID- 26874646 TI - Locomotive syndrome is associated not only with physical capacity but also degree of depression. AB - BACKGROUND: Reports of locomotive syndrome (LS) have recently been increasing. Although physical performance measures for LS have been well investigated to date, studies including psychiatric assessment are still scarce. Hence, the aim of this study was to investigate both physical and mental parameters in relation to presence and severity of LS using a 25-question geriatric locomotive function scale (GLFS-25) questionnaire. METHODS: 150 elderly people aged over 60 years who were members of our physical-fitness center and displayed well-being were enrolled in this study. Firstly, using the previously determined GLFS-25 cutoff value (=16 points), subjects were divided into two groups accordingly: an LS and non-LS group in order to compare each parameter (age, grip strength, timed-up-and go test (TUG), one-leg standing with eye open, back muscle and leg muscle strength, degree of depression and cognitive impairment) between the groups using the Mann-Whitney U-test followed by multiple logistic regression analysis. Secondly, a multiple linear regression was conducted to determine which variables showed the strongest correlation with severity of LS. RESULTS: We confirmed 110 people for non-LS (73%) and 40 people for LS using the GLFS-25 cutoff value. Comparative analysis between LS and non-LS revealed significant differences in parameters in age, grip strength, TUG, one-leg standing, back muscle strength and degree of depression (p < 0.006, after Bonferroni correction). Multiple logistic regression revealed that functional decline in grip strength, TUG and one-leg standing and degree of depression were significantly associated with LS. On the other hand, we observed that the significant contributors towards the GLFS-25 score were TUG and degree of depression in multiple linear regression analysis. CONCLUSIONS: The results indicate that LS is associated with not only the capacity of physical performance but also the degree of depression although most participants fell under the criteria of LS. PMID- 26874647 TI - Adherence to physical activity in an unsupervised setting: Explanatory variables for high attrition rates among fitness center members. AB - OBJECTIVES: To evaluate the attrition rate of members of a fitness center in the city of Rio de Janeiro and the potential explanatory variables for the phenomenon. DESIGN: An exploratory, observational study using a retrospective longitudinal frame. METHODS: The records of 5240 individuals, members of the fitness center between January-2005 and June-2014, were monitored for 12 months or until cancellation of membership, whichever occurred first. A Cox proportional hazard regression model was adjusted to identify variables associated to higher risk of 'abandonment' of activities. This study was approved by Southern Cross University's Human Research Ethics Committee (approval number: ECN-15-176). RESULTS: The general survival curve shows that 63% of new members will abandon activities before the third month, and less than 4% will remain for more than 12 months of continuous activity. The regression model showed that age, previous level of physical activity, initial body mass index and motivations related to weight loss, hypertrophy, health, and aesthetics are related to risk of abandonment. Combined, those variables represent an important difference in the probability to abandon the gym between individuals with the best and worse combination of variables. Even individuals presenting the best combination of variables still present a high risk of abandonment before completion of 12 months of fitness center membership. CONCLUSIONS: Findings can assist in the identification of high risk individuals and therefore help in the development of strategies to prevent abandonment of physical activity practice. PMID- 26874648 TI - Rates of attrition, non-compliance and missingness in randomized controlled trials of child physical activity interventions using accelerometers: A brief methodological review. AB - OBJECTIVES: The purpose of this brief review was to describe the missingness, from both attrition and non-compliance, during physical activity randomized controlled trials among children which have used accelerometers to measure physical activity. DESIGN: Systematic review. METHODS: Using a previously published search strategy, an updated search of the literature was performed in the MEDLINE database for articles published from 1996 to February 2015 identifying physical activity RCTs in children (ages 2-18) measuring physical activity using accelerometers. Rates of attrition and non-compliance were extracted from identified articles. Twenty-three independent studies provided complete attrition and non-compliance data and were included. RESULTS: The mean attrition rate was 11.5% (SD 10.1%, range 0-30.9%). The mean accelerometer non compliance rate at baseline was 22.7% (SD 16.4%, range 1.7-67.8%) and 29.6% (SD 19.4%, range 3.3-70.1%) at follow-up. The mean total study missingness was 37.4% (SD 20.2%, range 3.3-75.4%) and ranged from 3.3% to 75.4%. There was large variation in how missingness was accounted for between studies. There were no statistically significant differences in missingness between study characteristics including sample size, participant age, intervention setting, duration of follow-up, whether physical activity was the primary outcome, and weartime compliance criteria. CONCLUSIONS: Missingness is common among randomized controlled trials using accelerometry in children and is currently handled inconsistently. Researchers must plan for high levels of missingness in study design and account for missingness in reporting and analyses of trial outcomes. PMID- 26874649 TI - The organization and contribution of helicases to RNA splicing. AB - Splicing is an essential step of gene expression. It occurs in two consecutive chemical reactions catalyzed by a large protein-RNA complex named the spliceosome. Assembled on the pre-mRNA substrate from five small nuclear proteins, the spliceosome acts as a protein-controlled ribozyme to catalyze the two reactions and finally dissociates into its components, which are re-used for a new round of splicing. Upon following this cyclic pathway, the spliceosome undergoes numerous intermediate stages that differ in composition as well as in their internal RNA-RNA and RNA-protein contacts. The driving forces and control mechanisms of these remodeling processes are provided by specific molecular motors called RNA helicases. While eight spliceosomal helicases are present in all organisms, higher eukaryotes contain five additional ones potentially required to drive a more intricate splicing pathway and link it to an RNA metabolism of increasing complexity. Spliceosomal helicases exhibit a notable structural diversity in their accessory domains and overall architecture, in accordance with the diversity of their task-specific functions. This review summarizes structure-function knowledge about all spliceosomal helicases, including the latter five, which traditionally are treated separately from the conserved ones. The implications of the structural characteristics of helicases for their functions, as well as for their structural communication within the multi-subunits environment of the spliceosome, are pointed out. PMID- 26874650 TI - Corrigendum to "MiRNA-26b regulates the expression of cyclooxygenase-2 in desferrioxamine-treated CNE cells" [FEBS Lett. 584 (5) (2010) 961-967]. PMID- 26874652 TI - Re: physician suicide and physician health programs. PMID- 26874654 TI - Chemotherapy at First Diagnosis of Advanced Prostate Cancer - Revolution or Evolution? Findings from a British Uro-oncology Group UK Survey to Evaluate Oncologists' Views on First-line Docetaxel in Combination with Androgen Deprivation Therapy in Castrate-sensitive Metastatic and High-risk/Locally Advanced Prostate Cancer. AB - AIMS: There have been three randomised trials investigating docetaxel in combination with androgen deprivation therapy as first-line therapy for hormone sensitive metastatic and locally advanced/high-risk prostate cancer. The largest of these studies, UK STAMPEDE trial, recently presented in June 2015. The aim of this survey was to evaluate if oncologists' practice has changed as a result of these studies, or if their practice is likely to change in different clinical settings in the future. MATERIALS AND METHODS: The British Uro-oncology Group issued a semi-structured online questionnaire to its membership of 160 specialist urological oncologists practising in the UK. Links to the abstracts of GETUG-AFU 15, E3805 CHAARTED and STAMPEDE were attached with the survey for respondents to review before completing the survey. RESULTS: In total, 111 participants completed the survey; 87% stated that STAMPEDE will influence their clinical practice in the future. Almost all (96%) would offer docetaxel with androgen deprivation therapy to men presenting with high volume metastatic prostate cancer. Fewer oncologists would offer this treatment to men with low volume metastatic prostate cancer, locally advanced or relapsed disease. Various patient and disease-related factors were considered in decision making, as well as resource implications. CONCLUSIONS: This survey reports oncologists' attitudes towards a major change in practice in the standard of care for men with newly diagnosed advanced prostate cancer in the UK. The survey highlighted the complexities surrounding the clinical implementation of the data from these studies, including changes in referral pathways, with the early involvement of oncologists in such patients' care, increases in workloads for oncologists and chemotherapy units and the need for national approval for re-imbursement of these treatments. PMID- 26874653 TI - Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. AB - Despite advances in the diagnosis and management of idiopathic noncirrhotic portal hypertension, its pathogenesis remains elusive. Insight may be gained from study of early-onset familial idiopathic noncirrhotic portal hypertension, in which Mendelian mutations may account for disease. We performed exome sequencing of eight subjects from six kindreds with onset of portal hypertension of indeterminate etiology during infancy or childhood. Three subjects from two consanguineous families shared the identical rare homozygous p.N46S mutation in DGUOK, a deoxyguanosine kinase required for mitochondrial DNA replication; haplotype sharing demonstrated that the mutation in the two families was inherited from a remote common ancestor. All three affected subjects had stable portal hypertension with noncirrhotic liver disease for 6-16 years of follow-up. This mutation impairs adenosine triphosphate binding and reduces catalytic activity. Loss-of-function mutations in DGUOK have previously been implicated in cirrhosis and liver failure but not in isolated portal hypertension. Interestingly, treatment of patients with human immunodeficiency viral infection with the nucleoside analogue didanosine is known to cause portal hypertension in a subset of patients and lowers deoxyguanosine kinase levels in vitro; the current findings implicate these effects on deoxyguanosine kinase in the causal mechanism. CONCLUSION: Our findings provide new insight into the mechanisms mediating inherited and acquired noncirrhotic portal hypertension, expand the phenotypic spectrum of DGUOK deficiency, and provide a new genetic test for a specific cause of idiopathic noncirrhotic portal hypertension. (Hepatology 2016;63:1977-1986). PMID- 26874655 TI - Injury, inflammation and the emergence of human-specific genes. AB - In light of the central role of inflammation in normal wound repair and regeneration, we hypothesize that the preponderance of human-specific genes expressed in human inflammatory cells is commensurate with the genetic versatility of inflammatory response and the emergence of injuries associated with uniquely hominid behaviors, like a bipedal posture and the use of tools, weapons and fire. The hypothesis underscores the need to study human-specific signaling pathways in experimental models of injury and infers that a selection of human-specific genes, driven in part by the response to injury, may have facilitated the emergence of multifunctional genes expressed in other tissues. PMID- 26874656 TI - Radiation therapy (RT) after breast-conserving surgery (BCS) in 2015--The year of radiation therapy advances. AB - Surgery associated with radiation therapy is the standard treatment for early breast cancer. This paper reviews the new evidence on local control and survival, the indications of lymph-node irradiation, and the long-term results of large prospective trials. New shorter fractionation schemes allow a reduction in the constraints of daily treatment courses over several weeks, and recent technical improvements in treatment delivery will improve cancer outcomes in terms of local control, decreased toxicity and long-term sequelae. Research should focus on identifying molecular markers for radiation sensitivity while designing specific, targeted modulators of the radiation response in early breast cancer. PMID- 26874657 TI - Caring for one and all - Exploring ethical challenges in an ICU. AB - This discussion paper explores some of the complex ethical and moral issues confronting contemporary critical care nurses. In contemporary healthcare discussions, there is an increased appreciation of the complexity of ethical challenges, the multiplicity of stakeholders and that a broad range of possible and practical outcomes exist. Furthermore, many scholars also acknowledge the limitations of principle based ethical frameworks. In seeking to build critical care nurses' capacity to negotiate the complex - and often conflicting - ethical challenges, the authors have adopted a person-centred, values-based approach in this case study. Furthermore, by exploring these complex issues, this paper supports and builds upon critical care nurses' decision making capacities in the clinical area. This case study has been purposefully left open-ended with the aim of inviting the reader to consider the questions posed in a collegial, collaborative manner within the particular context in which she/he is embedded. PMID- 26874658 TI - Tumefactive gallbladder sludge: the MRI findings. AB - AIM: To evaluate the conventional and diffusion-weighted magnetic resonance imaging (MRI) images of tumefactive gallbladder sludge. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Between January 2006 and January 2015, 3478 patients were diagnosed with gallbladder sludge by ultrasonography (US). Of them, 12 patients (eight male, four female; mean age, 63.6 years) with 12 tumefactive gallbladder sludge lesions, who underwent subsequent MRI for further evaluation within 1 month, were included in this study. Data regarding the clinical features, presence of enhancement, and signal intensities of the T2-, T1-, and diffusion-weighted images were collected. RESULTS: All cases of tumefactive sludge were detected incidentally. None of the patients had any predisposing factors for biliary sludge. The tumefactive gallbladder sludge was predominantly seen as a well-defined mass-like lesion. It showed hyperintensity on T1-weighted images (91.7%, 11/12), and variable signal intensities on T2-weighted images. Most of the tumefactive sludge lesions showed no enhancement on the dynamic phases (90%, 9/10). There were no cases with diffusion restriction. Among the patients with follow-up US data (n=7), all the lesions were found to have either disappeared or decreased in size. CONCLUSION: Although tumefactive gallbladder sludge on US can mimic gallbladder cancer, its hyperintensity on a T1-weighted image, and the absence of enhancement and diffusion restriction on MRI images can be helpful for differentiating it from a tumorous condition. PMID- 26874659 TI - Re: Differentiation of pleomorphic adenoma and Warthin's tumour of the salivary gland: is long-to-short ratio a useful parameter? PMID- 26874660 TI - Interventional stem cell therapy. AB - The ability to deliver cells in appropriate doses to their targeted site of action is a well-known obstacle to optimising stem cell therapy. Systemic administration of cells results in pulmonary "trapping," which significantly decreases the number of available circulating cells to impact underlying disorders. Directed delivery of stem cells in interventional radiology may provide an additional option for bypassing the lungs, as well as introduce novel potential avenues for decreasing doses required to effect cellular therapy, efficiently obtain local paracrine effects, and/or to simplify targeting strategies. PMID- 26874661 TI - Oblique vein of the left atrium - The Marshall vein. PMID- 26874662 TI - Nutrition and health claims in products directed at children via television in Spain in 2012. AB - OBJECTIVE: To describe the use of nutrition and health claims in products directed at children via television in Spain and to analyse their nutrient profile. METHODS: A cross-sectional study of television food advertisements over 7 days in five Spanish television channels popular among children. The products were classified as core, non-core or miscellaneous, and as either healthy or less healthy, according to the United Kingdom Nutrient Profile Model. We registered all claims contained on the product (packaging and labelling) and its advertisement. We calculated the frequency distributions of health and nutrition claims. RESULTS: During the 420hours of broadcasting, 169 food products were identified, 28.5% in the dairy group and 60.9% in the non-core category. A total of 53.3% of products contained nutrition claims and 26.6% contained health claims; 62.2% of the products with claims were less healthy. Low-fat dairy products were the food category containing the highest percentage of health and nutrition claims. CONCLUSION: Over half of all food products marketed to children via television in Spain made some type of nutrition or health claim. Most of these products were less healthy, which could mislead Spanish consumers. PMID- 26874663 TI - [Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage]. AB - OBJECTIVE: To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. MATERIALS AND METHODS: Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervals<20minutes and>=20minutes. Obstetrical and neonatal issues were analyzed according to the duration oxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. RESULTS: Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals>=20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth<=7.10 and/or 5minutes score d'Apgar<=7, was higher if oxytocin augmentation intervals were<20minutes (12.1% vs 4.3%; P=0.002). CONCLUSION: Our study demonstrated an increased risk of PPH for primiparous women in spontaneous labour who received oxytocin with augmentation intervals shorter than 20minutes. PMID- 26874665 TI - [Pictures balance for optimal surgical management of pelvic endometriosis. Imaging and surgery of endometriosis]. AB - Endometriosis is a frequent benign pathology that is found in 10-15% of women and in 20% of infertile women. It has an impact on fertility, but also in everyday life. If medical treatment fails, surgical treatment can be offered to the patient. To provide adequate treatment and give clearer information to patients, it seems essential to achieve an optimal preoperative imaging assessment. Thus, the aim of this work is to define the information expected by the surgeon and the indications of each imaging test for each compartment of the pelvis, allowing an ideal surgical management of pelvic endometriosis. We will not discuss imaging techniques' principles and we will not develop the indications and surgical techniques. PMID- 26874666 TI - [Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review]. AB - OBJECTIVE: The purpose of this review is to assess the preoperative management in case of recurrent cervical cancer, to assess patients for a surgical curative treatment. METHODS: English publications were searched using PubMed and Cochrane Library. RESULTS: In the purpose of curative surgery, pelvic exenteration required clear margins. Today, only half of pelvic exenteration procedures showed postoperative clear margins. Modern imaging (RMI and Pet-CT) does not allow defining local extension of microcopic disease, and thus postoperative clear margins. Despite the same generic term of pelvic exenteration, there is a wide heterogeneity in surgical procedures in published cohorts. CONCLUSION: Because clear margins are required for curative pelvic exenteration, but are not predictable by preoperative assessment. The larger surgery, i.e. the infra elevator exenteration with vulvectomy, could be the logical surgical choice to increase the rate of clear margins and therefore, recurrent cervical carcinoma patient survival. PMID- 26874667 TI - ["The two fontanelles sign": A new clinical sign for quality control in fetal head position diagnosis?] AB - OBJECTIVES: Determine the frequency at which palpation of two fontanelles is possible, in order to describe a new clinical diagnosis approach: "the two fontanelles sign". MATERIALS AND METHODS: Descriptive study established in the obstetric and gynecology department at Lyon-Sud university hospital between March and November 2013. We followed-up one thousand successive singleton deliveries in cephalic presentation after 30 weeks of gestation. Before starting expulsive efforts, the number of fontanelles perceived (1, 2 or any) was documented. If the number of fontanelles were not noted, the patient was excluded. RESULTS: Nine hundred and seventy-eight patients were included. In 39.3% of cases (n=384), 2 fontanelles were found, in 57.5% (n=563) only one and in 3.2% (n=31), none. CONCLUSION: Both fontanelles palpation is frequently possible and enables quality control of fetal head presentation variety without ultrasound assessment. In order to prove the reliability of clinical examination, study comparing presentation ultrasonography and digital examination finding 2 fontanelles is needed. PMID- 26874668 TI - A SimpleProbe((r)) real-time PCR assay for differentiating the cytochrome b M121I mutation in clinical specimens from dogs infected with Babesia gibsoni. AB - Babesia gibsoni (B. gibsoni) causes a canine tick-borne disease worldwide. The substitution of methionine with isoleucine (M121I) in the cytochrome b (CYTb) gene of B. gibsoni was identified as being associated with atovaquone resistance. Rapid identification of the drug-resistant strain is required to select a more effective combination of drugs, e.g., from atovaquone and azithromycin (AA) to clindamycin, diminazene, and imidocarb (CDI) combination. A SimpleProbe((r)) real time PCR assay was designed to detect the single nucleotide polymorphism at nucleotide 363 in CYTb gene of B. gibsoni and the sensitivity and specificity were evaluated by comparing the results from the conventional DNA sequencing method. Eighty-nine clinical blood samples were collected and analyzed in parallel with the SimpleProbe((r)) assay and DNA sequencing. The assay identified 50 of 54 nt363G samples and had a sensitivity of 92.6% and a specificity of 100%. Thirty nt363T samples were correctly identified, as well, with a sensitivity of 100% and a specificity of 73.2%. However, this assay identified only one of 17 nt363A samples; the other 16 samples were misidentified as nt363T. The sensitivity of the nt363A identification was only 5.9%, and the specificity was 100%. When detecting the M121I mutation, 42 of 42 mutant samples were identified, with a sensitivity of 100%, and 45 of 47 wild type samples were identified, with a specificity of 95.7%. In conclusion, the SimpleProbe((r)) assay could be used to detect the M121I mutation of the B. gibsoni CYTb from clinical specimens. This assay provides a reliable and sensitive tool for differentiating between the atovaquone-resistant strain and the non-resistant strain. PMID- 26874669 TI - Bacterial agents in 248 ticks removed from people from 2002 to 2013. AB - A retrospective study was conducted to analyze the tick species removed from people and to detect tick-infecting bacteria in the specimens collected over the past 10 years at the reference center for rickettsioses, Marseille, France. A total of 248 ticks were removed from 200 people, including Dermacentor (73), Rhipicephalus (67), Ixodes (60), Amblyomma (8), Argas (3), Hyalomma (1), and Haemaphysalis (1) species. Bacterial DNA was detected in 101 ticks: Rickettsia slovaca (34%) and Rickettsia raoultii (23%) were detected in Dermacentor ticks; Rickettsia conorii (16%) and Rickettsia massiliae (18%) were found in Rhipicephalus ticks; and Anaplasma phagocytophylum (5%), Borrelia spp. (8%) and Rickettsia spp. (2%) were detected in Ixodes ticks. Among the bitten people for which clinical data and laboratory samples were available, tick borne diseases were confirmed in 11 symptomatic individuals. PMID- 26874670 TI - First record of Babesia sp. in Antarctic penguins. AB - This is the first reported case of Babesia sp. in Antarctic penguins, specifically a population of Chinstrap penguins (Pygoscelis antarctica) in the Vapour Col penguin rookery in Deception Island, South Shetlands, Antarctica. We collected peripheral blood from 50 adult and 30 chick Chinstrap penguins. Examination of the samples by microscopy showed intraerythrocytic forms morphologically similar to other avian Babesia species in 12 Chinstrap penguin adults and seven chicks. The estimated parasitaemias ranged from 0.25*10(-2)% to 0.75*10(-2)%. Despite the low number of parasites found in blood smears, semi nested PCR assays yielded a 274 bp fragment in 12 of the 19 positive blood samples found by microscopy. Sequencing revealed that the fragment was 97% similar to Babesia sp. 18S rRNA from Australian Little Penguins (Eudyptula minor) confirming presence of the parasite. Parasite prevalence estimated by microscopy in adults and chicks was higher (24% vs. 23.3%, respectively) than found by semi nested PCR (16% vs. 13.3% respectively). Although sampled penguins were apparently healthy, the effect of Babesia infection in these penguins is unknown. The identification of Babesia sp. in Antarctic penguins is an important finding. Ixodes uriae, as the only tick species present in the Antarctic Peninsula, is the key to understanding the natural history of this parasite. Future work should address the transmission dynamics and pathogenicity of Babesia sp. in Chinstrap penguin as well as in other penguin species, such as Gentoo penguin (Pygoscelis papua) and Adelie penguin (Pygoscelis adeliae), present within the tick distribution range in the Antarctic Peninsula. PMID- 26874671 TI - Pararenal Aortic Ulcer Repair. AB - OBJECTIVE/BACKGROUND: In order to investigate techniques and outcomes of pararenal penetrating aortic ulcer (PAU) repair, a retrospective cohort study was performed. METHODS: Over the 6 year study period, 12 patients treated for a pararenal PAU were included. Outcome measures included technical success, survival, and peri-operative complications, as well as stent patency. RESULTS: Treatment modalities included hybrid procedures with endovascular aneurysm repair (EVAR) and bypass grafting, chimney EVAR (Ch-EVAR), and fenestrated EVAR (FEVAR). Four of the 12 patients were symptomatic, and eight patients underwent elective surgery. The technical success rate was 100%. Symptom resolution was recorded in all symptomatic patients immediately post-operatively. Complications encountered included one type I endoleak in a patient who underwent Ch-EVAR, and one case of post-operative stroke, paralysis, and death in a patient who underwent FEVAR. No adverse events were recorded in the remaining 10 patients. The PAU protrusion distance was significantly greater in symptomatic patients. Perforation and leakage were more prevalent in patients with pre-operative abdominal or back pain. CONCLUSION: Encouraging results of endovascular treatment of pararenal PAUs were observed. One major and fatal complication was encountered, which underlines the complexity and risks of the techniques. Another patient required re intervention owing to an endoleak following off label use of covered stents for Ch-EVAR. FEVAR, which generally requires a custom made graft, was increasingly applied over the study period, potentially because of an increased awareness of this distinct pathology allowing for elective procedure planning. Ch-EVAR and hybrid procedures were predominantly used in symptomatic patients, whereas FEVAR was the preferred elective treatment option. PMID- 26874673 TI - Compliance with carbapenem guidelines in a university hospital. AB - OBJECTIVE: We aimed to evaluate carbapenem prescription compliance with guidelines for nosocomial and community-acquired infections. PATIENTS AND METHODS: We conducted a prospective study over a four-month period at our university hospital. We included all adult and pediatric hospitalized patients who had received at least one dose of carbapenem. Data was collected from patients' medical records (hard copy and computerized data; CristalLink software). Compliance with guidelines was assessed by two infectious disease specialists. Assessment criteria included indication, antibiotic choice, dosage, and treatment duration. RESULTS: We included 152 patients in the study (65.4% of men). Carbapenem prescription was appropriate for 76.3% of prescriptions. The use of carbapenems was considered appropriate for 73.9% of empirical prescriptions and for 77.8% of documented prescriptions. Non-compliance with guidelines was mainly due to prescriptions for community-acquired infections. Antibiotic de escalation could not be initiated in 40.3% of patients and was only initiated in 51.7% of patients for whom it could be considered. Although the average treatment duration was 7.5 days, 23.7% of patients received carbapenems for more than 10 days. CONCLUSION: These results highlight the need for a strong carbapenem stewardship program in our hospital. PMID- 26874672 TI - Suplatast tosilate alleviates nasal symptoms through the suppression of nuclear factor of activated T-cells-mediated IL-9 gene expression in toluene-2,4 diisocyanate-sensitized rats. AB - Histamine H1 receptor (H1R) gene is upregulated in patients with pollinosis; its expression level is highly correlated with the nasal symptom severity. Antihistamines are widely used as allergy treatments because they inhibit histamine signaling by blocking H1R or suppressing H1R signaling as inverse agonists. However, long-term treatment with antihistamines does not completely resolve toluene-2,4-diisocyanate (TDI)-induced nasal symptoms, although it can decrease H1R gene expression to the basal level, suggesting additional signaling is responsible for the pathogenesis of the allergic symptoms. Here, we show that treatment with suplatast tosilate in combination with antihistamines markedly alleviates nasal symptoms in TDI-sensitized rats. Suplatast suppressed TDI induced upregulation of IL-9 gene expression. Suplatast also suppressed ionomycin/phorbol-12-myristate-13-acetate-induced upregulation of IL-2 gene expression in Jurkat cells, in which calcineurin (CN)/nuclear factor of activated T-cells (NFAT) signaling is known to be involved. Immunoblot analysis demonstrated that suplatast inhibited binding of NFAT to DNA. Furthermore, suplatast suppressed ionomycin-induced IL-9 mRNA upregulation in RBL-2H3 cells, in which CN/NFAT signaling is also involved. These data suggest that suplatast suppressed NFAT-mediated IL-9 gene expression in TDI-sensitized rats and this might be the underlying mechanism of the therapeutic effects of combined therapy of suplatast with antihistamine. PMID- 26874674 TI - [Obstructive sleep apnea syndrome. Is it a risk factor for diabetic retinopathy?]. AB - PURPOSE: The goal of our study was to evaluate the prevalence of diabetic retinopathy in type 2 diabetic patients with obstructive sleep apnea syndrome. PATIENTS AND METHODS: We performed a comparative study including 60 type 2 diabetics separated into 2 groups: a 1st group composed of 20 patients with obstructive sleep apnea syndrome and a 2nd group composed of 40 patients without this syndrome. The two groups were matched for age and length of diabetes. All patients underwent a complete ophthalmic examination. RESULTS: In both groups, the mean patient age was 59 years, the diabetes had been present for an average of 10 years, and the HbA1c was 10%. Diabetic retinopathy was diagnosed in 11 patients from the 1st group (55%) and 6 cases from the 2nd group (15%) (P=0.03). Non-proliferative and proliferative retinopathy were found in 7 cases (35%) and 4 cases (20%), respectively, in the 1st group and in 3 cases (7.5%) in the 2nd group for both types (P=0.03 and P=0.042, respectively). Diabetic macular edema was observed in 4 patients (20%) in the 1st group and 2 patients (5%) in the 2nd group (P=0.04). CONCLUSION: Obstructive sleep apnea syndrome is an independent risk factor for the appearance and aggravation of diabetic retinopathy. This underscores the importance of systematic screening for, and timely management of, sleep apnea. PMID- 26874676 TI - Influence of metal(loid) bioaccumulation and maternal transfer on embryo-larval development in fish exposed to a major coal ash spill. AB - In December 2008, an earthen retaining wall at the Tennessee Valley Authority (TVA) Kingston Fossil Fuel Plant failed and released 4.1 millionm(3) of coal ash to rivers flowing into Watts Bar Reservoir in east Tennessee, United States (U.S.). As part of a comprehensive effort to evaluate the risks to aquatic resources from this spill - the largest in U.S. history - we compared bioaccumulation and maternal transfer of selenium (Se), arsenic (As), and mercury (Hg) in adult redear sunfish (Lepomis macrolophus), collected two years after the spill from both coal-ash exposed and non-exposed areas of the Emory and Clinch Rivers, with the success of embryo-larval development in their offspring. Whole body and ovary concentrations of Se in female sunfish at three study sites downstream of the spill were significantly elevated (site means=4.9-5.3 and 6.7 9.0mg/kg d.w. whole body and ovary concentrations, respectively) compared with concentrations in fish from reference sites upstream of the spill site (2.2 3.2mg/kg d.w. for whole bodies and 3.6-4.8mg/kg d.w. for ovaries). However, Se concentrations in coal ash-exposed areas remain below proposed U.S. Environmental Protection Agency (USEPA) criteria for the protection of aquatic life. Site-to site variation in fish concentrations of As and Hg were not well-correlated with ash-exposure, reflecting the multiple sources of these metal(loid)s in the affected watersheds. In 7-day laboratory tests of embryos and larvae derived from in vitro crosses of eggs and sperm from these field-collected sunfish, fertilization success, hatching success, embryo-larval survival, and incidences of developmental abnormalities did not differ significantly between ash-exposed and non-exposed fish. Furthermore, these developmental endpoints were not correlated with whole body or ovary concentrations of Se, As, or Hg in the maternal fish, or with fish size, ovary weight, or gonadal-somatic indices. Results from this and related studies associated with the Kingston coal ash spill are consistent with proposed USEPA fish-based water quality criteria for Se, and to date continue to suggest that long-term exposures to sediment containing residual ash may not present a significant chronic risk to fish populations exposed to this major coal ash release. PMID- 26874675 TI - New insight into the effects of heparinoids on complement inhibition by C1 inhibitor. AB - Complement activation is of major importance in numerous pathological conditions. Therefore, targeted complement inhibition is a promising therapeutic strategy. C1 esterase inhibitor (C1-INH) controls activation of the classical pathway (CP) and the lectin pathway (LP). However, conflicting data exist on inhibition of the alternative pathway (AP) by C1-INH. The inhibitory capacity of C1-INH for the CP is potentiated by heparin and other glycosaminoglycans, but no data exist for the LP and AP. The current study investigates the effects of C1-INH in the presence or absence of different clinically used heparinoids on the CP, LP and AP. Furthermore, the combined effects of heparinoids and C1-INH on coagulation were investigated. C1-INH, heparinoids or combinations were analysed in a dose dependent fashion in the presence of pooled serum. Functional complement activities were measured simultaneously using the Wielisa((r)) -kit. The activated partial thrombin time was determined using an automated coagulation analyser. The results showed that all three complement pathways were inhibited significantly by C1-INH or heparinoids. Next to their individual effects on complement activation, heparinoids also enhanced the inhibitory capacity of C1 INH significantly on the CP and LP. For the AP, significant potentiation of C1 INH by heparinoids was found; however, this was restricted to certain concentration ranges. At low concentrations the effect on blood coagulation by combining heparinoids with C1-INH was minimal. In conclusion, our study shows significant potentiating effects of heparinoids on the inhibition of all complement pathways by C1-INH. Therefore, their combined use is a promising and a potentially cost-effective treatment option for complement-mediated diseases. PMID- 26874677 TI - Application of molecular endpoints in early life stage salmonid environmental biomonitoring. AB - Molecular endpoints can enhance existing whole animal bioassays by more fully characterizing the biological impacts of aquatic pollutants. Laboratory and field studies were used to examine the utility of adopting molecular endpoints for a well-developed in situ early life stage (eyed embryo to onset of swim-up fry) salmonid bioassay to improve diagnostic assessments of water quality in the field. Coastal cutthroat trout (Oncorhynchus clarki clarki) were exposed in the laboratory to the model metal (zinc, 40MUg/L) and the polycyclic aromatic hydrocarbon (pyrene, 100MUg/L) in water to examine the resulting early life stage salmonid responses. In situ field exposures and bioassays were conducted in parallel to evaluate the water quality of three urban streams in British Columbia (two sites with anthropogenic inputs and one reference site). The endpoints measured in swim-up fry included survival, deformities, growth (weight and length), vitellogenin (vtg) and metallothionein (Mt) protein levels, and hepatic gene expression (e.g., metallothioneins [mta and mtb], endocrine biomarkers [vtg and estrogen receptors, esr] and xenobiotic-metabolizing enzymes [cytochrome P450 1A3, cyp1a3 and glutathione transferases, gstk]). No effects were observed in the zinc treatment, however exposure of swim-up fry to pyrene resulted in decreased survival, deformities and increased estrogen receptor alpha (er1) mRNA levels. In the field exposures, xenobiotic-metabolizing enzymes (cyp1a3, gstk) and zinc transporter (zntBigM103) mRNA were significantly increased in swim-up fry deployed at the sites with more anthropogenic inputs compared to the reference site. Cluster analysis revealed that gene expression profiles in individuals from the streams receiving anthropogenic inputs were more similar to each other than to the reference site. Collectively, the results obtained in this study suggest that molecular endpoints may be useful, and potentially more sensitive, indicators of site-specific contamination in real-world, complex exposure scenarios in addition to whole body morphometric and physiological measures. PMID- 26874678 TI - [Update of hidradenitis suppurativa in Primary Care]. AB - Hidradenitis suppurativa is a prevalent disease that is noted for its clinical variability and by its severe impact on quality of life. A meticulous scientific literature review is presented in this article in order to give an update on what is known on this condition. Primary Care physicians obviously play an important role in the early diagnosis and management of hidradenitis suppurativa. This review aims to provide a current and practical overview about this disease in order to optimise the healthcare for these patients by making the best use of available resources. PMID- 26874679 TI - Pulmonary recurrence in patients with endometrial cancer. AB - BACKGROUND: In this article, we aimed to define the clinical, pathological, and surgical factors predicting pulmonary recurrence (PR) and determining survival after PR in patients with endometrial cancer. METHODS: Thirty-six (2.7%) patients were analyzed who suffered pulmonary failure in the first recurrence out of 1345 patients who had at least extrafascial hysterectomy plus bilateral salpingo oophorectomy for endometrial cancer between January 1993 and May 2013. The recurrence was designated as an isolated PR in cases of the presence of recurrence only in the lung, while it was called a synchronized PR if the patient had extrapulmonary recurrence in addition to PR. RESULTS: In the multivariate analysis in the entire cohort, only International Federation of Gynecology and Obstetrics stage was an independent prognostic factor for PR. Two-year overall survival (OS) was 52% in patients with PR. In the univariate analysis, early International Federation of Gynecology and Obstetrics stage, absence of lymphatic metastasis, negative lymphovascular space invasion, absence of cervical invasion, negative adnexal spread, negative peritoneal cytology, negative omental metastasis, adjuvant radiotherapy after initial surgery, isolated PR, and chemotherapy upon recurrence were associated with improved OS after PR. The OS was 54 months for patients with isolated PR, while it was 10 months for patients who had synchronized PR. Furthermore, OS was 43 months and 13 months for the patients who took chemotherapy and radiotherapy, respectively. CONCLUSION: Advanced stage is associated with PR. If recurrence is only in the lung, survival is better. Systemic treatment after PR is associated with improved survival. However, multi-center studies are required to standardize the treatment for PR. PMID- 26874680 TI - Isolation of Streptococcus pyogenes from children with pharyngitis and emm type analysis. AB - BACKGROUND: The group A streptococcus (GAS) M protein, encoded by the emm gene, acts as a major virulence factor. Emm-typing is the GAS gold standard molecular typing and is based on the DNA sequence of the nucleotides of the emm gene. The aim of the present study was to isolate GAS from patients and to detect the emm types of the isolates using emm typing. METHODS: A total of 1000 throat samples were collected from patients with pharyngitis referred to Aboozar Children's Hospital in Ahvaz, Iran. We performed antimicrobial susceptibility testing on all isolates using the Kirby-Bauer disk diffusion method. Additionally, amplification of the emm gene was performed using polymerase chain reaction using the standard primers and described protocol. RESULTS: From all throat samples screened, 25 isolates (2.5%) were identified as GAS. Antibiotic susceptibility testing revealed that all the GAS isolates were susceptible to penicillin and erythromycin, but 44% showed resistance to vancomycin. Based on polymerase chain reaction for the emm gene, the obtained emm types were: emm-3, observed in 20 isolates (80%); emm-1 observed in four isolates (16%); and emm-75 observed in one isolate (4%). CONCLUSION: The result of the present study showed that penicillin and erythromycin are still the most effective antibiotics against the organism. The emm typing revealed that emm type-3 was detected in most of the isolates from patients with purulent pharyngitis. On the basis of the findings of this study, we may conclude that emm typing provides new insights on the genetic diversity of the M proteins, and is of demonstrable value for molecular studies of GAS. PMID- 26874681 TI - Efficacy of continuous theta burst stimulation of the primary motor cortex in reducing migraine frequency: A preliminary open-label study. AB - BACKGROUND: Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long-lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocols. This pilot study investigated whether continuous theta burst stimulation (cTBS) on the primary motor cortex reduced headache frequency in patients with migraine. METHODS: Nine patients with migraine were recruited into our study. All patients received 20 cTBS sessions (bursts of 3 50-Hz TMS pulses at 200-ms intervals for 40 seconds), administered every weekday for 4 consecutive weeks. All patients kept headache diaries for 4 weeks before stimulation (baseline; T1), during stimulation (T2), and 4 weeks after stimulation (T3). The primary outcome measures were the changes of total headache and migraine days from baseline (Wilcoxon signed-rank test; T2 and T3 vs. T1). RESULTS: The number of total headache days was reduced at T2 and T3 compared with T1 [9.4 +/- 6.2 days (p = 0.024) and 8.7 +/- 10.1 days (p = 0.012) vs. 13.4 +/- 10.1 days]. The number of migraine days was also reduced at T2 and T3 compared with T1 [2.9 +/- 2.7 days (p = 0.021) and 1.0 +/- 1.6 days (p = 0.008) vs. 8.6 +/- 8.7 days]. CONCLUSION: Our results indicate that cTBS on the primary motor cortex might reduce the number of total headache and migraine days in patients with migraine. However, large-scale randomized controlled trials are necessary to further validate the findings. PMID- 26874682 TI - Venous thromboembolism and risk of cancer in patients with diabetes mellitus. AB - AIM: Venous thromboembolism (VTE) has long been regarded as a marker of underlying malignancy in the general population. Patients with diabetes mellitus are at increased risk of developing VTE, but it is unclear whether VTE in diabetes patients is also a harbinger of occult cancer. METHODS: From Danish medical health databases, we identified all diabetes patients (N=8783) with a first-time diagnosis of VTE during 1978-2011. We followed the patients until a first-time diagnosis of cancer, emigration, death, or study end, whichever came first. We calculated one-year absolute cancer risk and overall and site-specific standardized incidence ratios (SIRs) for cancer based on national cancer incidence. RESULTS: During the total study period 878 cancers were observed. The one-year absolute cancer risk was 4.1% and the corresponding SIR was 3.28 (95% confidence interval [CI]: 2.94-3.64). The highest SIRs were observed for cancers of the gallbladder and biliary tract (SIR 13.59; 6.77-24.31), the pancreas (SIR 10.16; 6.85-14.50), the ovary (SIR 9.85; 5.63-16.00), and the liver (SIR 9.39; 4.30-17.84). After the first year of follow-up, the overall cancer SIR associated with VTE and diabetes decreased to 1.05 (95% CI: 0.97-1.15). CONCLUSIONS: VTE may be a marker of underlying cancer in patients with diabetes mellitus. PMID- 26874683 TI - Qualitative examination of cognitive change during PTSD treatment for active duty service members. AB - The current study investigated changes in service members' cognitions over the course of Cognitive Processing Therapy (CPT) for posttraumatic stress disorder (PTSD). Sixty-three active duty service members with PTSD were drawn from 2 randomized controlled trials of CPT-Cognitive Only (CPT-C). Participants wrote an impact statement about the meaning of their index trauma at the beginning and again at the end of therapy. Clauses from each impact statement were qualitatively coded into three categories for analysis: assimilation, accommodation, and overaccommodation. The PTSD Checklist, Posttraumatic Symptom Scale-Interview Version, and the Beck Depression Inventory-II were administered at baseline and posttreatment. Repeated measures analyses documented a significant decrease in the percentage of assimilated or overaccommodated statements and an increase in the percentage of accommodated statements from the beginning to the end of treatment. Changes in accommodated statements over the course of treatment were negatively associated with PTSD and depression symptom severity, while statements indicative of overaccommodation were positively associated with both PTSD and depression symptom severity. Treatment responders had fewer overaccommodated and more accommodated statements. Findings suggest that CPT-C changes cognitions over the course of treatment. Methodological limitations and the lack of association between assimilation and PTSD symptom severity are further discussed. PMID- 26874687 TI - Occupational injuries in times of labour market flexibility: the different stories of employment-secure and precarious workers. AB - BACKGROUND: The relationship between labour market flexibility, job insecurity and occupational injuries is not univocal. The literature generally focuses on the temporary character of work arrangements rather than on the precarity of careers. The aim of this paper is to identify, without defining a priori what a precarious career is, the most common professional profiles of young people who entered the labour market in the 2000s and to correlate them with occupational injury risks. METHODS: Using the Whip-Salute database, which combines individual work and health histories, we selected the subjects under 30 years of age whose first appearance in the database is dated after 2000. The occupational history of each individual between 2000 and 2005 was described according to 6 variables (type of entry contract, number of contracts, number of jobs, economic activities, work intensity and duration of the longest period of non-employment). Workers were grouped into homogeneous categories using cluster analysis techniques, which enable to identify different career profiles. Injury rates were calculated for each cluster, and compared within and between the groups. RESULTS: We selected 56,760 workers in the study period, who were classified in 6 main career profiles. About 1/3 of the subjects presented an employment-secure career profile, while about 45 % of them were classified into 3 clusters showing precarious career profiles with different work intensities. Precarious workers present significantly higher injury rates than those with secure careers, with an increase in risk between 24 and 57 % (p < 0.05). The comparison of injury rates at the beginning and at the end of the study period revealed a significant decrease in all clusters, but the gap between secure and precarious workers remained wide. CONCLUSIONS: Cluster analysis allowed to identify career patterns with clearly different characteristics. A positive association between injury risk and the level of career fragmentation was found. The association cannot be fully interpreted in a causal way, since reversed causality and selection processes may be in action. However the study indicates a disadvantage for precarious workers, who face significantly higher risks of both minor and severe injuries. PMID- 26874684 TI - Function and regulation of TRPM7, as well as intracellular magnesium content, are altered in cells expressing DeltaF508-CFTR and G551D-CFTR. AB - Cystic fibrosis (CF), one of the most common fatal hereditary disorders, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene product is a multidomain adenosine triphosphate binding cassette (ABC) protein that functions as a chloride (Cl(-)) channel that is regulated by intracellular magnesium [Mg(2+)]i. The most common mutations in CFTR are a deletion of a phenylalanine residue at position 508 (DeltaF508-CFTR, 70-80 % of CF phenotypes) and a Gly551Asp substitution (G551D-CFTR, 4-5 % of alleles), which lead to decreased or almost abolished Cl(-) channel function, respectively. Magnesium ions have to be finely regulated within cells for optimal expression and function of CFTR. Therefore, the melastatin-like transient receptor potential cation channel, subfamily M, member 7 (TRPM7), which is responsible for Mg(2+) entry, was studies and [Mg(2+)]i measured in cells stably expressing wildtype CFTR, and two mutant proteins (DeltaF508-CFTR and G551D CFTR). This study shows for the first time that [Mg(2+)]i is decreased in cells expressing DeltaF508-CFTR and G551D-CFTR mutated proteins. It was also observed that the expression of the TRPM7 protein is increased; however, membrane localization was altered for both DeltaF508del-CFTR and G551D-CFTR. Furthermore, both the function and regulation of the TRPM7 channel regarding Mg(2+) is decreased in the cells expressing the mutated CFTR. Ca(2+) influx via TRPM7 were also modified in cells expressing a mutated CFTR. Therefore, there appears to be a direct involvement of TRPM7 in CF physiopathology. Finally, we propose that the TRPM7 activator Naltriben is a new potentiator for G551D-CFTR as the function of this mutant increases upon activation of TRPM7 by Naltriben. PMID- 26874688 TI - GRG Profiles: George Triadafilopoulos. PMID- 26874685 TI - Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon. AB - Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress. PMID- 26874686 TI - Deep characterization of blood cell miRNomes by NGS. AB - A systematic understanding of different factors influencing cell type specific microRNA profiles is essential for state-of-the art biomarker research. We carried out a comprehensive analysis of the biological variability and changes in cell type pattern over time for different cell types and different isolation approaches in technical replicates. All combinations of the parameters mentioned above have been measured, resulting in 108 miRNA profiles that were evaluated by next-generation-sequencing. The largest miRNA variability was due to inter individual differences (34 %), followed by the cell types (23.4 %) and the isolation technique (17.2 %). The change over time in cell miRNA composition was moderate (<3 %) being close to the technical variations (<1 %). Largest variability (including technical and biological variance) was observed for CD8 cells while CD3 and CD4 cells showed significantly lower variations. ANOVA highlighted that 51.5 % of all miRNAs were significantly influenced by the purification technique. While CD4 cells were least affected, especially miRNA profiles of CD8 cells were fluctuating depending on the cell purification approach. To provide researchers access to the profiles and to allow further analyses of the tested conditions we implemented a dynamic web resource. PMID- 26874689 TI - Histological Assessment of NAFLD. AB - Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of histological lesions ranging from steatosis to a complex pattern with hepatocyte injury and inflammation in an appropriate clinical context. The disease has been artificially dichotomized into NAFL (steatosis) and NASH (steatosis with hepatocellular injury and inflammation), but it is increasingly clear that intermediate patterns may exist. More than NASH, the stage of fibrosis was shown to govern prognosis, and for such evaluation, a liver biopsy of adequate size and width is needed. Like for any other chronic liver diseases, semi-quantitative histologic scores have been proposed. They are not useful in clinical practice but concur to categorize homogeneous group of patients according to their histology. Pediatric NAFLD is a growing concern. While a subgroup of children may harbor different but characteristic histological patterns, most of them display a mixed pattern or features similar to the adults. Today, liver histology is the mainstay for clinical trials. Biopsy is used both for enrollment and for assessing benefit of clinical trials. End points such as reversion of NASH or regression of fibrosis are acceptable but require a clear histological definition. PMID- 26874690 TI - Dysphagia Lusoria: An Unexpected Sequelum of Cardiothoracic Surgery. PMID- 26874692 TI - Tired of Hepatitis B? PMID- 26874694 TI - Fractionating power and outlet stream polydispersity in asymmetrical flow field flow fractionation. Part I: isocratic operation. AB - Asymmetrical flow field-flow fractionation (As-FlFFF) has become the most commonly used of the field-flow fractionation techniques. However, because of the interdependence of the channel flow and the cross flow through the accumulation wall, it is the most difficult of the techniques to optimize, particularly for programmed cross flow operation. For the analysis of polydisperse samples, the optimization should ideally be guided by the predicted fractionating power. Many experimentalists, however, neglect fractionating power and rely on light scattering detection simply to confirm apparent selectivity across the breadth of the eluted peak. The size information returned by the light scattering software is assumed to dispense with any reliance on theory to predict retention, and any departure of theoretical predictions from experimental observations is therefore considered of no importance. Separation depends on efficiency as well as selectivity, however, and efficiency can be a strong function of retention. The fractionation of a polydisperse sample by field-flow fractionation never provides a perfectly separated series of monodisperse fractions at the channel outlet. The outlet stream has some residual polydispersity, and it will be shown in this manuscript that the residual polydispersity is inversely related to the fractionating power. Due to the strong dependence of light scattering intensity and its angular distribution on the size of the scattering species, the outlet polydispersity must be minimized if reliable size data are to be obtained from the light scattering detector signal. It is shown that light scattering detection should be used with careful control of fractionating power to obtain optimized analysis of polydisperse samples. Part I is concerned with isocratic operation of As-FlFFF, and part II with programmed operation. PMID- 26874693 TI - Inhibition-based first-generation electrochemical biosensors: theoretical aspects and application to 2,4-dichlorophenoxy acetic acid detection. AB - In this work, several theoretical aspects involved in the first-generation inhibition-based electrochemical biosensor measurements have been discussed. In particular, we have developed a theoretical-methodological approach for the characterization of the kinetic interaction between alkaline phosphatase (AlP) and 2,4-dichlorophenoxy acetic acid (2,4-D) as representative inhibitor studied by means of cyclic voltammetry and amperometry. Based on these findings, a biosensor for the fast, simple, and inexpensive determination of 2,4-D has been developed. The enzyme has been immobilized on screen-printed electrodes (SPEs). To optimize the biosensor performances, several carbon-based SPEs, namely graphite (G), graphene (GP), and multiwalled carbon nanotubes (MWCNTs), have been evaluated. AlP was immobilized on the electrode surface by means of polyvinyl alcohol with styryl-pyridinium groups (PVA-SbQ) as cross-linking agent. In the presence of ascorbate 2-phosphate (A2P) as substrate, the herbicide has been determined, thanks to its inhibition activity towards the enzyme catalyzing the oxidation of A2P to ascorbic acid (AA). Under optimum experimental conditions, the best performance in terms of catalytic efficiency has been demonstrated by MWCNTs SPE-based biosensor. The inhibition biosensor shows a linearity range towards 2,4-D within 2.1-110 ppb, a LOD of 1 ppb, and acceptable repeatability and stability. This analysis method was applied to fortified lake water samples with recoveries above 90%. The low cost of this device and its good analytical performances suggest its application for the screening and monitoring of 2,4-D in real matrices. PMID- 26874691 TI - The Importance of Intestinal Eotaxin-1 in Inflammatory Bowel Disease: New Insights and Possible Therapeutic Implications. AB - BACKGROUND: Involvement of eotaxin-1 in inflammatory bowel disease has been previously suggested and increased levels of eotaxin-1 have been described in both ulcerative colitis and in Crohn's disease. The association between serum levels of eotaxin-1 and that within the colonic mucosa has not been well defined, as is the potential therapeutic value of targeting eotaxin-1. AIMS: To characterize serum and intestinal wall eotaxin-1 levels in various inflammatory bowel disease patients and to explore the effect of targeting eotaxin-1 by specific antibodies in dextran sodium sulfate-induced colitis model. METHODS: Eotaxin-1 levels were measured in colonic biopsies and in the sera of 60 ulcerative colitis patients, Crohn's disease patients and healthy controls. We also followed in experimental colitis the effect of targeting eotaxin-1 by a monoclonal antibody. RESULTS: Colon eotaxin-1 levels were significantly increased in active but not in quiescent ulcerative colitis and Crohn's disease patients compared to healthy controls. Levels of eotaxin-1 in the colon were correlated with eosinophilia only in tissues from active Crohn's disease patients. Our results did not show any statistically significant change in serum eotaxin-1 levels among ulcerative colitis, Crohn's disease and healthy controls. Moreover, we demonstrate that in dextran sodium sulfate-induced colitis, targeting of eotaxin-1 with 2 injections of anti eotaxin-1 monoclonal antibody ameliorates disease activity along with decreasing colon weight and improving histologic inflammation. CONCLUSION: Eotaxin-1 is increasingly recognized as a major mediator of intestinal inflammation. Our preliminary human and animal results further emphasize the value of targeting eotaxin-1 in inflammatory bowel disease. PMID- 26874695 TI - Prevalence of presbyopia in a semi-urban population of southwest, Nigeria: a community-based survey. AB - Uncorrected presbyopia is a major cause of poor near vision in the developing countries. To determine the prevalence and demographic characteristics of presbyopia among adult populations (40 years and above) in a sub-urban population, southwest Nigeria, a population-based cross-sectional study was carried out from April to May 2014. A multi-stage sampling method was used to select eligible respondents. All participants had distance visual acuity assessment done and participants with visual acuity of less than 6/6 were refracted. Near vision was then assessed at 40 cm with distance correction in place if required. Information on near vision was obtained from the participants using interviewer administered questionnaires. Data collected were analysed using SPSS version 22. A total of 440 subjects aged 40 years and above were studied. Prevalence of presbyopia was 75 % and was significantly associated with increasing age. There was higher prevalence of presbyopia among females than males (76.3 % vs. 73.5 %), though not statistically significant. Also prevalence of presbyopia was not significantly associated with educational and occupational status in the study. This study demonstrated a high prevalence of presbyopia. There is need for improved awareness on presbyopia screening and available correction in the local government. PMID- 26874698 TI - SIU Newsletter - March 2016. PMID- 26874696 TI - Emerging Histopathological and Genetic Parameters of Pituitary Adenomas: Clinical Impact and Recommendation for Future WHO Classification. AB - The review assesses immunohistochemical findings of somatostatin receptors and of metalloproteinases in different pituitary adenoma types and the significance of molecular genetic data. Current evidence does not support routine immunohistochemical assessment of somatostatin or dopamine receptor subtype expression on hormone-secreting or nonfunctioning pituitary adenomas. Further prospective studies are needed to define its role for clinical decision making. Until then we suggest to restrict membrane receptor profiling to individual cases or for study purposes. The problems of adenoma expansion and invasion are discussed. Despite partially contradictory publications, proteases clearly play a major role in permission of infiltrative growth of pituitary adenomas. Therefore, detection of at least MMP-2, MMP-9, TIMP-2, and uPA seems to be justified. Molecular characterization is important for familial adenomas, adenomas in MEN, Carney complex, and McCune-Albright syndrome and can gain insight into pathogenesis of sporadic adenomas. PMID- 26874699 TI - Erratum to: Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate. PMID- 26874697 TI - Skp2 Regulates the Expression of MMP-2 and MMP-9, and Enhances the Invasion Potential of Oral Squamous Cell Carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck regions and accounts for more than 90 % of cancers in the oral cavity. S-phase kinase-associated protein-2 (Skp2) is a member of the F-box protein family and the substrate recognition subunit of the Skp1-Cullin-F box protein E3 ubiquitin ligase complex. Skp2 is oncogenic and overexpressed in human cancers. The aims of the present study were to determine the clinicopathological significance of Skp2 in OSCC and clarify its function in OSCC cell lines in vitro. Multiple methods including immunohistochemical staining, RT-PCR, western blotting, migration and invasion assays, and siRNA transfection were employed in order to investigate the clinicopathological significance and molecular function of Skp2 in OSCC. The overexpression of Skp2 was more frequent in OSCC than in the normal oral epithelium. It was also more frequently detected in cancers with higher grades according to the T classification, N classification, and pattern of invasion. The high-Skp2 expression group had a significantly poorer prognosis, at 30.1 %, than that of the low-expression group, at 63.0 %. The downregulation of Skp2 decreased migration and invasion potentials in HSC3 cells. Moreover, the suppression of Skp2 reduced the enzyme activities of MMP-2 and MMP-9 via Sp1. Skp2 may be a prognostic factor in OSCC patients, and may also play crucial roles in the migration and invasion potentials of OSCC cells. PMID- 26874700 TI - The role of dietary creatine. AB - The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in mother's milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799-1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease. PMID- 26874701 TI - 6-(4-Amino-2-butyl-imidazoquinolyl)-norleucine: Toll-like receptor 7 and 8 agonist amino acid for self-adjuvanting peptide vaccine. AB - Generally, small peptides by themselves are weak to induce antibody responses. Toll-like receptor (TLR) ligands are attractive candidates of vaccine adjuvants to improve their antigenicity. The covalent conjugation of TLR ligands with antigens to produce self-adjuvanting peptide vaccine is a promising approach. Based on the structure of TLR7/8 ligands, a series of synthetic amino acids 6 imidazoquinolyl-norleucines were synthesized, wherein an imidazoquinoline structure as the TLR7/8 agonistic pharmacophores was constructed on the epsilon NH2 group of Lys. Of them, 6-(4-amino-2-butyl-imidazoquinolyl)-norleucine showed the most potent TLR7 and TLR8 agonistic activities with EC50 values of 8.55 and 106 MUM, respectively. Subsequently, mice were immunized with the influenza A virus M2e antigen mixed with or covalently conjugated to the TLR7/8 agonist amino acid, which led to induction of M2e specific antibody productions in the absence of other adjuvant. We successfully developed a novel efficient tool for self adjuvanting peptide vaccines targeting TLR7/8. PMID- 26874702 TI - Comparative study of the P2X gene family in animals and plants. AB - P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while group-specific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies. PMID- 26874703 TI - Ablation for Persistent Atrial Fibrillation-Is There a Role for More Than PVI? AB - OPINION STATEMENT: Persistent atrial fibrillation (AF) is a prevalent condition that can be difficult to treat medically, and an ablation strategy is often sought. Currently, the cornerstone of AF ablation strategies is pulmonary vein isolation (PVI). Unfortunately, the single procedure success rates are limited, particularly when long-term outcomes (>1 year) are considered. As a result, the most recent consensus statement recommends that in patients with persistent AF a more extensive ablation be considered. Many additive procedural approaches to PVI have been investigated. These include electrical compartmentalization of the atria with linear lesions (LLs), ablation of complex fractionated atrial electrograms (CFAEs), ablation of the dominant frequency (DF) signals, and focal impulse and rotor modulation (FIRM) ablation. Each of these approaches has demonstrated degrees of additive success when performed with a PVI in patients with persistent AF. This review provides an in-depth discussion of these techniques, their successes in treating persistent AF, and their shortcomings. PMID- 26874704 TI - A Diagnostic and Therapeutic Approach to Arrhythmias in Cardiac Sarcoidosis. AB - OPINION STATEMENT: Cardiac sarcoidosis is a protean disease, capable of causing nearly any cardiac abnormality. Electrical abnormalities including heart block and ventricular tachyarrhythmias are some of the most feared manifestations of cardiac sarcoidosis. Despite increasing awareness, cardiac sarcoidosis remains underdiagnosed in clinical practice, and as a result, many patients do not receive potentially disease-altering immunosuppressant therapy. In this review, we discuss cardiac sarcoidosis and its management, focusing diagnostic and therapeutic approaches to arrhythmias in cardiac sarcoidosis. PMID- 26874705 TI - Evaluation and Management of Concomitant Hypertrophic Obstructive Cardiomyopathy and Valvular Aortic Stenosis. AB - OPINION STATEMENT: The dilemma of the patient with both AS and LVOTO is now commonly encountered in clinical practice; indeed, physicians must be aware of the complex interaction and coexistent nature of both diseases, especially as both HOCM and TAVR have increased in awareness and prevalence. Importantly, the clinician must be aware of the complex interplay hemodynamically, with the two diseases confusing the TTE imaging and potentially affecting each other anatomically and clinically. There is no set guideline on how to approach this from a surgical or percutaneous approach, but we have outlined a set of recommendations which should serve the clinician and patient well. The three cases that are presented illustrate that methodical diagnosis in addition to the order of treatment do indeed matter. In the first case, there was AS and an underestimated LVOT gradient that was also present. Once the AS was corrected, the true LVOT gradient potential was evidenced and she decompensated, likely because there was a rapid decrease in afterload. Patients with concomitant LVOTO are not able to adjust quickly to the hemodynamic changes created by the rapid decline in afterload, as, for example, in HOCM patients who receive nitroglycerin. The second case demonstrated that when the LVOTO was severe and the AS nonsignificant (mild or moderate), the patient was able to live without symptoms for several years after successful alcohol septal ablation (ASA). She eventually needed an aortic valve and mitral valve replacement but that was postponed for several years until the AS became more significant, and the surgical risk was lowered by the elimination of the need for concomitant myectomy. In the last case, the patient was able to have both an ASA and TAVR within 3 months of each other without hemodynamic compromise. Indeed, this latter therapy sequence may be the best way to treat patients with both diseases in the future, as both ASA and TAVR continue to evolve into intermediate and lower-risk patient populations and the safety of ASA continues to be evident. PMID- 26874706 TI - New Diagnostic and Therapeutic Strategies for Pulmonary Hypertension Associated with Left Heart Disease. AB - OPINION STATEMENT: Pulmonary hypertension associated with left heart disease (PH LHD) is a challenging entity to both diagnose and treat. A lack of consensus definitions, poorly understood pathophysiology, and the dynamic nature of hemodynamic assessments make this disease entity both underrecognized and misdiagnosed frequently. Diagnosing PH-LHD is crucial, because it not only alters management, but also has a direct effect on morbidity and mortality and ultimately leads to worse outcomes in this patient population. Though medical management remains challenging in these patients, an appropriate diagnosis, with careful assessment of hemodynamic parameters, can allow for appropriate advanced medical therapies and for improved quality of life. PMID- 26874708 TI - Regenerative Medicine: Potential Mechanisms of Cardiac Recovery in Takotsubo Cardiomyopathy. AB - OPINION STATEMENT: Takotsubo cardiomyopathy is an increasingly reported cause of acute chest pain and acute heart failure and is often associated with significant hemodynamic compromise. The illness is remarkable for the reversibility in systolic dysfunction seen in the disease course. While the pathophysiology of takotsubo syndrome is not completely elucidated, research suggests the presence of a cytoprotective process that allows the myocardium to recover following the inciting insult. Here, we summarize molecular and histologic studies exploring the response to injury in takotsubo disease and provide some discussion on how they may contribute to further investigations in cardiac recovery and regeneration. PMID- 26874707 TI - Unprotected Left Main Disease: Indications and Optimal Strategies for Percutaneous Intervention. AB - OPINION STATEMENT: Although the incidence of left main (LM) coronary artery disease is relatively low in patients undergoing routine angiography, it is a common presentation in patients with acute coronary syndromes. With the current interventional tools and techniques, percutaneous intervention for LM disease has become a viable alternative to the traditional coronary artery bypass grafting. Factors that contribute to the success and appropriateness of percutaneous intervention for LM disease include coronary anatomy and patient-specific factors such as left ventricular function. Multiple considerations should be taken into account prior to intervention, including hemodynamic support if necessary, intravascular imaging to guide therapy, and stent technique. This review provides an overview of the current body of literature to support the use of percutaneous intervention in LM disease and serves as guideline for the interventionalist approaching LM revascularization. PMID- 26874709 TI - Importance of organellar proteins, protein translocation and vesicle transport routes for pollen development and function. AB - KEY MESSAGE: Protein translocation. Cellular homeostasis strongly depends on proper distribution of proteins within cells and insertion of membrane proteins into the destined membranes. The latter is mediated by organellar protein translocation and the complex vesicle transport system. Considering the importance of protein transport machineries in general it is foreseen that these processes are essential for pollen function and development. However, the information available in this context is very scarce because of the current focus on deciphering the fundamental principles of protein transport at the molecular level. Here we review the significance of protein transport machineries for pollen development on the basis of pollen-specific organellar proteins as well as of genetic studies utilizing mutants of known organellar proteins. In many cases these mutants exhibit morphological alterations highlighting the requirement of efficient protein transport and translocation in pollen. Furthermore, expression patterns of genes coding for translocon subunits and vesicle transport factors in Arabidopsis thaliana are summarized. We conclude that with the exception of the translocation systems in plastids-the composition and significance of the individual transport systems are equally important in pollen as in other cell types. Apparently for plastids only a minimal translocon, composed of only few subunits, exists in the envelope membranes during maturation of pollen. However, only one of the various transport systems known from thylakoids seems to be required for the function of the "simple thylakoid system" existing in pollen plastids. In turn, the vesicle transport system is as complex as seen for other cell types as it is essential, e.g., for pollen tube formation. PMID- 26874710 TI - Breeding for plant heat tolerance at vegetative and reproductive stages. AB - KEY MESSAGE: Thermotolerant crop research. Global warming has become a serious worldwide threat. High temperature is a major environmental factor limiting crop productivity. Current adaptations to high temperature via alterations to technical and management systems are insufficient to sustain yield. For this reason, breeding for heat-tolerant crops is in high demand. This review provides an overview of the effects of high temperature on plant physiology, fertility and crop yield and discusses the strategies for breeding heat-tolerant cultivars. Generating thermotolerant crops seems to be a challenging task as heat sensitivity is highly variable across developmental stages and processes. In response to heat, plants trigger a cascade of events, switching on numerous genes. Although breeding has made substantial advances in developing heat tolerant lines, the genetic basis and diversity of heat tolerance in plants remain largely unknown. The development of new varieties is expensive and time consuming, and knowledge of heat tolerance mechanisms would aid the design of strategies to screen germplasm for heat tolerance traits. However, gains in heat tolerance are limited by the often narrow genetic diversity. Exploration and use of wild relatives and landraces in breeding can increase useful genetic diversity in current crops. Due to the complex nature of plant heat tolerance and its immediate global concern, it is essential to face this breeding challenge in a multidisciplinary holistic approach involving governmental agencies, private companies and academic institutions. PMID- 26874726 TI - Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo. AB - Recently, several studies have shown that piperlongumine (PL) can selectively kill cancer cells by targeting reactive oxygen species (ROS). However, the potential therapeutic effects and detailed mechanism of PL in gastric cancer are still not clear. In the current report, we found that PL significantly suppressed gastric cancer both in vitro and in vivo. PL obviously increased ROS generation in gastric cancer cells. Anti-oxidant glutathione (GSH) and N-acetyl-L-cysteine (NAC) can abrogate PL-induced gastric cancer cell death and proliferation inhibition. GADD45alpha was induced in PL-treated cancer cells and led to G2/M phase arrest, whereas genetic depletion of GADD45alpha by small interfering RNAs (siRNAs) could partly reverse PL-induced cell cycle arrest in gastric cancer cells. Interestingly, we also found that PL treatment decreased the expression of telomerase reverse transcriptase (TERT) gene, which plays an essential role in cancer initiation and progression. Our findings thus revealed a potential anti tumor effect of PL on gastric cancer cells and may have therapeutic implications. PMID- 26874727 TI - Computational prediction of Mycoplasma hominis proteins targeting in nucleus of host cell and their implication in prostate cancer etiology. AB - Cancer has long been assumed to be a genetic disease. However, recent evidence supports the enigmatic connection of bacterial infection with the growth and development of various types of cancers. The cause and mechanism of the growth and development of prostate cancer due to Mycoplasma hominis remain unclear. Prostate cancer cells are infected and colonized by enteroinvasive M. hominis, which controls several factors that can affect prostate cancer growth in susceptible persons. We investigated M. hominis proteins targeting the nucleus of host cells and their implications in prostate cancer etiology. Many vital processes are controlled in the nucleus, where the proteins targeting M. hominis may have various potential implications. A total of 29/563 M. hominis proteins were predicted to target the nucleus of host cells. These include numerous proteins with the capability to alter normal growth activities. In conclusion, our results emphasize that various proteins of M. hominis targeted the nucleus of host cells and were involved in prostate cancer etiology through different mechanisms and strategies. PMID- 26874728 TI - HSPB1 polymorphisms might be associated with radiation-induced damage risk in lung cancer patients treated with radiotherapy. AB - Several studies investigating the association between heat shock protein beta-1 (HSPB1) polymorphisms and radiation-induced damage in lung cancer patients administrated with radiotherapy have derived conflicting results. This meta analysis aimed to assess the association between the HSPB1 genes' (rs2868370 and rs2868371) polymorphisms and the risk of radiation-induced damage in lung cancer patients. After an electronic literature search, four articles including six studies were found to be eligible for this meta-analysis. No association was observed between rs2868370 genotypes and radiation-induced damage risk. However, rs2868371 showed a statistically increased risk of radiation-induced damage under CC vs. CG/GG model (OR = 1.59, 95 % CI = 1.10-2.29). Subgroup analysis by ethnicity showed that the genotypes of rs2868371 were also associated with a significantly increased risk of radiation-induced damage in CC vs. CG/GG model (OR = 1.86, 95 % CI = 1.21-2.83) among mixed ethnicities which are mainly comprised of white people. When the data was stratified by organ-damaged, a significant association was only observed in the esophagus group (OR = 2.94, 95 % CI = 1.35-6.37, for CC vs. CG/GG model). In conclusion, the present study demonstrated that the rs2868371 genotypes of HSPB1 might be associated with radiation-induced esophagus damage risk, especially in Caucasians but not in the Asian population. PMID- 26874729 TI - The contribution of flowering time and seed content to uneven ripening initiation among fruits within Vitis vinifera L. cv. Pinot noir clusters. AB - MAIN CONCLUSION: Ripening initiation-associated hormonal changes and sugar accumulation for individual fruits differed by seed content and did not depend heavily on flowering time or duration from anthesis to clusters' onset of ripening. For Vitis vinifera, the ripening initiation of individual fruits in a cluster occurs unevenly. This developmental period is called veraison. Why individual fruits initiate ripening at different times is not well studied, though differences in seed content and unequal developmental durations that arise from asynchronous flowering within a cluster have been proposed. This study examined how much both variables contribute to individual fruits' ripening progress by mid-veraison, when half of berries in a cluster have initiated ripening, and whether either or both factors affect the timing of characteristic, ripening-initiation associated changes in abscisic acid and auxin before, at, and after veraison. Overall, developmental duration and flowering time did not sufficiently explain how far berries had progressed into the ripening stage because fruits did not require a fixed amount of time to initiate ripening. Fruits from early and late flowers but of similar seed content were able to initiate ripening at the same time despite differences in chronological age. This suggests either an early developmental enhancement occurred for late-initiated fruits or that flowering time is an inappropriate "day zero". Ultimately, only seed content was linked to the timing and magnitude of ripening-related hormone changes, supporting that seeds have a comparatively larger influence than flowering time on the ripening initiation of individual berries. More specifically, if the fraction of berry weight occupied by seed was high, then the initiation of ripening for that berry and its associated hormone changes were delayed relative to berries with less seed weight versus total berry weight. PMID- 26874730 TI - Necrotizing arteritis occurring in an intralobar pulmonary sequestration of a patient without systemic vasculitis syndrome. AB - Necrotizing arteritis is a complex lesion of pulmonary hypertension, as are plexiform lesions, and is classically recognized as grade 6 in the Heath and Edwards grading scheme for hypertensive pulmonary vascular disease. The vascular changes observed in intralobar pulmonary sequestration have been reported to be similar to those observed in pulmonary hypertension, such as plexiform lesions. However, necrotizing arteritis occurring in an intralobar sequestration of a patient without systemic vasculitis syndrome has never been reported to our knowledge. Here, we report a case of a 38-year-old woman with pulmonary sequestration detected on a medical checkup. She was treated with surgery, and subsequent pathological analyses revealed necrotizing vasculitis in her sequestrated lung. We suspected systemic vasculitis syndromes, such as Takayasu arteritis, polyarteritis nodosa, and antineutrophil cytoplasmic antibody associated vasculitis. However, physical and blood examination did not show any other abnormalities, and hence, she did not have systemic vasculitis syndrome. Immunohistochemical analyses of the resected specimen showed that inflammatory cells of the arteries were mainly composed of T lymphocytes. T-lymphocytic inflammation with little neutrophil and histiocyte infiltration may be a pathological feature of necrotizing arteritis observed in pulmonary sequestration. This is the first case to our knowledge of necrotizing arteritis in an intralobar pulmonary sequestration of a patient without systemic vasculitis syndrome. PMID- 26874731 TI - Nodal yield of neck dissections and influence on outcome in laryngectomized patients. AB - The appropriate extent of neck dissection (ND) in head and neck squamous cell carcinoma (SCC) continues to be investigated. This study aimed to determine whether the extent of ND as measured by nodal yield (NY) is a prognostic factor in patients undergoing primary total laryngectomy (TL) for advanced laryngeal SCC. A retrospective review at a tertiary referral centre identified 54 patients who underwent TL with elective (n = 39, cN0) or therapeutic (n = 15, cN+) ND with curative intent between 2002 and 2014. Survival analysis was obtained via regression analysis, calculated for overall (OS) and disease-free survival (DFS). Stage-independent 5-year OS was 32.1 %. Mean NY was 18.67 (standard deviation 9.898; range 0-45). The rate of cervical lymph node metastasis on pathology (pN+) was 27.8 %. Uni- and multivariate regression analysis detected no association between NY and OS or DFS (P >= 0.05). Advantages in OS and DFS were seen among patients without cervical lymph node metastasis (pN0) in comparison to those with pN+ necks (OS: hazard ratio [HR] 0.179; 95 % confidence interval [CI] 0.046 0.693; P = 0.013, and DFS: HR 0.190; 95 % CI 0.061-0.590; P = 0.004). ND resulted in pathologic upstaging of the neck in seven patients and downgrading in eight; increasing NY was not associated with an increased probability of a change in nodal stage. No significant association was found between NY and OS or DFS in patients undergoing TL with ND as primary therapy for advanced laryngeal SCC. PMID- 26874732 TI - Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis. AB - We sought to evaluate the efficacy and feasibility of superselective intra arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed. The ascending pharyngeal artery was targeted for the treatment of RPLN metastasis in 9 patients. The median total dose of cisplatin was 26.6 mg/m(2) (mean 31.5 mg/m(2), range 11.7-87.9 mg/m(2)). In the remaining patient, the RPLN was supplied by the ascending palatine artery. As grade 3 and 4 adverse effects, leukopenia was observed in three, mucositis in four and nausea in one patient. No neurological complications were observed in any patients. Metastatic RPLNs were evaluated as a complete response in all patients. There was no recurrence of RPLN metastasis in any patients. Four patients remain alive without any evidence of disease and six patients died of disease. The 5-year overall survival rate was 50 %. We have shown that superselective intra-arterial cisplatin infusion for RPLNs was a feasible and effective approach for HNSCC patients with RPLN metastasis. PMID- 26874733 TI - Predictors of post-treatment smoking and drinking behavior of head and neck cancer survivors: results of a population-based survey. AB - Predictors for smoking and alcohol drinking behavior were investigated in head and neck cancer survivors (HNCS) with survivorship of >=6 months. 165 HNCS registered in a regional cancer registry and treated 2005-2014 were included. Patients completed a survey including the Fagerstrom Test for nicotine dependence and the Alcohol Use Disorders Identification Test. Smoking and drinking cessation rates were 51 and 13 %, respectively. Multinomial logistic regression analyses showed that male patients [odds ratio (OR) 35.4; confidence interval (CI) 7.5 168.1; p < 0.0001], single persons (OR 9.9; CI 2.5-40.0; p = 0.001), and younger patients (OR 1.1; CI 1.0-1.1; p = 0.002) had significantly higher probability to be current smokers. Male gender (OR 48.7; CI 5.0-470.7; p < 0.0001) and younger age (OR 1.1; CI 1.0-1.3; p = 0.003) were predictors of risky alcohol consumption. Male, young, and single smoking and/or drinking HNCS should be stimulated to take part in smoking and/or alcohol drinking cessation programs. PMID- 26874734 TI - Cholesteatoma growth patterns: are there audiometric differences between posterior epitympanic and posterior mesotympanic cholesteatoma? AB - The objective of this is to verify whether the hearing impairment caused by posterior epitympanic differed from that caused by posterior mesotympanic cholesteatomas by a cross-sectional study. We evaluated 264 ears of patients with cholesteatoma, who had not been subjected to ear surgery. Otoendoscopy and pure tone audiometry were performed. Analyzed route involved in cholesteatoma formation: posterior epitympanic or posterior mesotympanic, air-bone gaps at 512 4000 Hz and pure-tone averages. The mean age of the patients enrolled in this study was 33.8 years, and 51.8 % of them was male. Posterior epitympanic cholesteatoma was found in 50.4 % of the study population. When the air-bone gaps were compared, the mesotympanic group had greater thresholds at 500, 2000 Hz, and a greater pure-tone average (P = 0.003, P = 0.03, and P = 0.02, respectively). Posterior mesotympanic cholesteatoma showed greater air-bone gaps thresholds at the speech frequencies than posterior epitympanic cholesteatoma did. Moreover, the two growth patterns were very similar with regard to all other audiometric parameters analyzed in this study. PMID- 26874735 TI - Systematic analytical characterization of new psychoactive substances: A case study. AB - New psychoactive substances (NPS) are synthesized compounds that are not usually covered by European and/or international laws. With a slight alteration in the chemical structure of existing illegal substances registered in the European Union (EU), these NPS circumvent existing controls and are thus referred to as "legal highs". They are becoming increasingly available and can easily be purchased through both the internet and other means (smart shops). Thus, it is essential that the identification of NPS keeps up with this rapidly evolving market. In this case study, the Belgian Customs authorities apprehended a parcel, originating from China, containing two samples, declared as being "white pigments". For routine identification, the Belgian Customs Laboratory first analysed both samples by gas-chromatography mass-spectrometry and Fourier Transform Infrared spectroscopy. The information obtained by these techniques is essential and can give an indication of the chemical structure of an unknown substance but not the complete identification of its structure. To bridge this gap, scientific and technical support is ensured by the Joint Research Centre (JRC) to the European Commission Directorate General for Taxation and Customs Unions (DG TAXUD) and the Customs Laboratory European Network (CLEN) through an Administrative Arrangement for fast recognition of NPS and identification of unknown chemicals. The samples were sent to the JRC for a complete characterization using advanced techniques and chemoinformatic tools. The aim of this study was also to encourage the development of a science-based policy driven approach on NPS. These samples were fully characterized and identified as 5F-AMB and PX-3 using (1)H and (13)C nuclear magnetic resonance (NMR), high-resolution tandem mass-spectrometry (HR-MS/MS) and Raman spectroscopy. A chemoinformatic platform was used to manage, unify analytical data from multiple techniques and instruments, and combine it with chemical and structural information. PMID- 26874736 TI - A snapshot on NPS in Italy: Distribution of drugs in seized materials analysed in an Italian forensic laboratory in the period 2013-2015. AB - The diffusion of New Psychoactive Substances (NPS) in the illicit drug market is a worldwide problem. The aim of the study is to describe the qualitative distribution of drugs of abuse in seized materials confiscated in the Italian territory over the last two years. Between 2013 and 2015 162 seizures of substances purchased through the Internet and confiscated by police authorities were analyzed: 35 seizures (22%) were crystals of 3-methylmethcathinone (3-MMC). Although 3-MMC is subject to the relevant legislation in Italy, it is not controlled in other countries such as the Netherlands, from which the shipments originated. 33 seizures (20%) were crystals of 4-methylethcathinone (4-MEC), 19 seizures (12%) were powders containing methylenedioxypyrovalerone (MDPV). N,N diallyl-5-methoxytryptamine (5-MeO-DALT) was identified in 5 powders, whereas ethylphenidate in six and pyrrolidinophenones in fourteen seized powders: 6 alpha PVP (alpha-pyrrolidinovalerophenone), 6 alpha-PHP (alpha-pyrrolidinohexiophenone) and 1 alpha-PVT (alpha-pyrrolidinopentiothiophenone). Other substances identified were cathinones such as pentedrone, methylone, buthylone, ethylone, methedrone, 3 CMC (3-chloromethcathinone), 3,4-dimethylmethcathinone (3,4-DMMC), flephedrone (4 fluoromethcathinone or 4-FMC), 2-FMC and 3-FMC (2- and 3-fluoromethcathinone), MPPP (4-methyl-alpha-pyrrolidinopropiophenone), bk-2C-B (2-amino-1-(4-bromo-2,5 dimethoxyphenyl)ethan-1-one). Other compounds were NM2AI (N-methyl-2 aminoindane), MPA (1-(thiophen-2-yl)-2-methylaminopropane), MTTA (mephtetramine), 4-APB and 6-APB (4- and 6- (2-aminopropyl)benzofuran), 2-fluoromethamphetamine, 1mCPP (1-meta-chlorophenylpiperazine) and diphenidine, detected for the first time in Europe. Only three seizures contained synthetic cannabinoids, consisting of herbal blends soaked in N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB48), or a mixture of 5-F-AKB48 and BB-22 (1-(cyclohexylmethyl)-8-quinolinyl ester-1H-indole-3-carboxylic acid). In some mixtures of drugs - such as granules 4-MEC and pentedrone were detected, also with traces of diphenidine on one occasion. In other cases 5-MeO-DALT, ethylphenidate and caffeine were mixed together. In one batch, the mixture was flephedrone and methoxethamine, whereas in another one the sample contained methylone, ethylone, methedrone, 4 fluoroamphetamine, 5-MeO-DALT and 5MeO-MiPT (N-methyl-N-isopropyl-5 methoxytryptamine). In 9 seizures, tablets shipped together with NPS were also found to contain sildenafil. The analyses performed on these seizures showed the presence of a wide number of NPS within the Italian boundaries coming from abroad, therefore this study confirms the threat for the public health, especially when the content of NPS being sold is not reported on the label or misleading. PMID- 26874737 TI - Non-oncology physician visits after diagnosis of cancer in adolescents and young adults. AB - PURPOSE: Health care needs of adolescents and young adults (AYAs) with cancer are probably different from other age groups. Studying their non-oncology physician visits in the first years after diagnosis may provide insight into the specific health problems AYA patients experience and thereby help to improve care for these patients. METHODS: Seven hundred seventy-four AYAs identified from a Canadian provincial registry diagnosed with cancer between ages 15 and 24 years in 1991/2001 were included, matched by birth year and sex to ten controls. Based on provincial health insurance plan records, we determined the number of family physician and non-cancer specialist visits in the 5 years after diagnosis (for patients) or inclusion (for controls). RESULTS: The percentage of patients visiting a non-cancer specialist decreased from 96 to 49 % over the 5-year period. The percentage visiting a family physician decreased from 96 to 84 %. Visits in all years were significantly higher than among controls. In the first year after diagnosis, many patients visited a non-cancer specialist or a family physician for neoplasm-related health problems (77 and 55 %, respectively). In addition, family physicians were also consulted for general age-specific problems, such as genitourinary symptoms CONCLUSIONS: In the first years after diagnosis of cancer in AYAs, both non-cancer specialist and family physician visits are common, although non-cancer specialist visits are less common and decline considerably faster than in younger children. IMPLICATIONS FOR CANCER SURVIVORS: The specific pattern of physician visits of this age group calls for care that is tailored to their specific needs. PMID- 26874738 TI - Virtual and simulated striated toolmarks for forensic applications. AB - Large numbers of experimental toolmarks of screwdrivers are often required in casework of toolmark examiners and in research environments alike, to be able to recover the angle of attack of a crime scene mark and to determine statistically meaningful properties of toolmarks respectively. However, in practice the number of marks is limited by the time needed to create them. In this article, we present an approach to predict how a striated mark of a particular tool would look like, using 3D surface datasets of screwdrivers. We compare these virtual toolmarks qualitatively and quantitatively with real experimental marks in wax and show that they are very similar. In addition we study toolmark similarity, dependent on the angle of attack, with a very high angular resolution of 1 degrees . The results show that for the tested type of screwdriver, our toolmark comparison framework yields known match similarity scores that are above the mean known non-match similarity scores, even for known match differences in angle of attack of up to 40 degrees . In addition we demonstrate an approach to automatically recover the angle of attack of an experimental toolmark and experiments yield high accuracy and precision of 0.618 +/- 4.179 degrees . Furthermore, we present a strategy to study the structural elements of striated toolmarks using wavelet analysis, and show how to use the results to simulate realistic toolmarks. PMID- 26874739 TI - Development and validation of a GC-MS method for nicotine detection in Calliphora vomitoria (L.) (Diptera: Calliphoridae). AB - Entomotoxicology is the application of toxicological methods and analytical procedures on necrophagous insects feeding on decomposing tissues to detect drugs and other chemical components, and their mechanisms affecting insect development and morphology and modifying the methodology for estimation of minimum time since death. Nicotine is a readily available potent poison. Because of its criminal use, a gas chromatography-mass spectrometry (GC-MS) method for the detection of nicotine in Calliphora vomitoria L. (Diptera: Calliphoridae) was developed and validated. Furthermore, the effect of nicotine on the development, growth rate, and survival of this blowfly was studied. Larvae were reared on liver substrates homogeneously spiked with measured amounts of nicotine (2, 4, and 6 ng/mg) based on concentrations that are lethal to humans. The results demonstrated that (a) the GC-MS method can detect both nicotine and its metabolite cotinine in immature C. vomitoria; (b) the presence of nicotine in the aforementioned three concentrations in food substrates did not modify the developmental time of C. vomitoria; (c) during the pupation period, larvae exposed to nicotine died depending on the concentration of nicotine in the substrate; and (d) the resultant lengths of larvae and pupae exposed to 4 and 6 ng/mg concentrations of nicotine were significantly shorter than those of the control. PMID- 26874742 TI - 5-Carba-pterocarpens: A new scaffold with anti-HCV activity. AB - The synthesis of a series of 5-carba-pterocarpens derivatives involving the cyclization of alpha-aryl-alpha-tetralones is described. Several compounds demonstrated potent activity and selectivity in vitro against HCV replicon reporter cells. The best profile in Huh7/Rep-Feo1b replicon reporter cells was observed with 2h (EC50 = 5.5 MUM/SI = 20), while 2e was the most active in Huh7.5 FGR-JC1-Rluc2A replicon reporter cells (EC50 = 1.5 MUM/SI = 70). Hydroxy groups at A- and D-rings are essential for anti-HCV activity, and substitutions in the A ring at positions 3 and 4 resulted in enhanced activity of the compounds. PMID- 26874740 TI - Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium. AB - INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model. METHODS: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163+/-31% vs. 13+/-14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery. PMID- 26874743 TI - Synthesis, biological evaluation and molecular modeling of pseudo-peptides based statine as inhibitors for human tissue kallikrein 5. AB - Human kallikrein 5 (KLK5) is a potential target for the treatment of skin inflammation and cancer. A new series of statine based peptidomimetic compounds were designed and synthesized through simple and efficient reactions. Some KLK5 inhibitors (2a-c compounds) were identified with nanomolar affinity showing Ki values of 0.12-0.13 MUM. Our molecular modeling studies suggest that the inhibitors binding at the KLK5 through H-bond interactions with key residues (mainly His108, Gln242, Gly243, Ser245, and Ser260), disrupting the correlated motions mainly among the Ile67-Tyr127, Glu128-Val187, and Gly237-Ser293 subdomains, which seems to be crucial for KLK5 activity. Therefore, we believe that these findings will significantly facilitate our understanding of the conformational dynamics in the course of KLK5 inhibition and, consequently, the development of more potent molecules as alternative for cancer treatment. PMID- 26874744 TI - Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers. AB - The cyclization of chalcones 3a-3u with 3-hydrazinyl-6-phenylpyridazine 7 under basic condition led to the formation of new pyrazoline derivatives 8a-8u. All final compounds were characterized by spectral and elemental analyses. They were screened for their antiproliferative activities against A549 (lung), HepG-2 (liver), CaCo-2 (intestinal) and MCF-7 (breast) cancer cell lines. Some of the synthesized compounds exhibited promising antiproliferative activities especially compound 8k with IC50 values of 8.33, 1.67 and 10 MUM against HepG-2, MCF-7 and CaCo-2 cancer cell lines, respectively. Moreover, their antiproliferative activity was due to apoptosis rather than necrosis induction except compound 8h which exhibited equal apoptotic and necrotic properties. Compound 8k showed 5 fold increase in caspase-3 activity indicating that the apoptosis proceeds via caspase-3 activation. PMID- 26874741 TI - The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity. AB - Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors. Herein we report our efforts towards identifying a potent and selective RET inhibitor using vandetanib 1 as the starting point for structure-based drug design. Phenolic anilinoquinazolines exemplified by 6 showed improved affinities towards RET but, unsurprisingly, suffered from high metabolic clearance. Efforts to mitigate the metabolic liability of the phenol led to the discovery that a flanking substituent not only improved the hepatocyte stability, but could also impart a significant gain in selectivity. This culminated in the identification of 36; a potent RET inhibitor with much improved selectivity against KDR. PMID- 26874745 TI - Optimal modified tracking performance for MIMO systems under bandwidth constraint. AB - This paper investigates the optimal modified tracking performance of multi-input multi-output (MIMO) networked control systems (NCSs) with bandwidth and channel noise constraints. A new modified tracking performance index is proposed which prevents variations in the tracking error from leading to invalid data where there is no integrator in the plant. An expression for the optimal modified tracking performance is obtained using a method which includes co-prime factorization, partial factorization, spectral decomposition and H2 norm. The obtained results show that the optimal modified tracking performance is influenced by the non-minimum phase (NMP) zeros, unstable poles, and their directions. Furthermore, the characteristics of the input signal, the modification factor, the bandwidth and the channel noise are also shown to be closely related to the optimal modified tracking performance. Finally, the efficiency of the result is verified using some typical examples. PMID- 26874746 TI - Enhancing public awareness and promoting co-responsibility for marine litter in Europe: The challenge of MARLISCO. AB - Marine litter is a pervasive and complex societal problem but has no simple solution. Inadequate practices at all levels of production-use-disposal contribute to accumulation of waste on land and at sea. Enhanced societal awareness but also co-responsibility across different sectors and improved interactions between stakeholders are necessary. MARLISCO was a European initiative, which developed and implemented activities across 15 countries. It worked towards raising societal awareness and engagement on marine litter, through a combination of approaches: public exhibitions in over 80 locations; a video competition involving 2100 students; and a legacy of educational and decision-supporting tools. 12 national participatory events designed to facilitate dialogue on solutions brought together 1500 stakeholders and revealed support for cross-cutting, preventive measures. Evaluation during implementation shows that these activities are effective in improving individuals' perceptions about the problem but also commitment in being part of the solution. This paper summarises MARLISCO's approach and highlights a selection of outcomes. PMID- 26874747 TI - Paralytic shellfish toxin production by the dinoflagellate Alexandrium pacificum (Chinhae Bay, Korea) in axenic, nutrient-limited chemostat cultures and nutrient enriched batch cultures. AB - Blooms of Alexandrium pacificum (formerly Alexandrium tamarense) are common in Chinhae Bay (Korea), presumably linked to anthropogenic eutrophication. Here we examine PSP toxin content and composition in axenic chemostat and batch cultures of A. pacificum using growth conditions that differed according to dilution rate, nutrient limitations, and enrichments. Phosphate (P)-limited cells in chemostat cultures had higher toxin content and a toxin composition that differed from that of nitrogen (N)-limited cells at the highest growth rates. Therefore, toxin composition changes do occur in axenic cultures of A. pacificum following extended growth under steady state conditions. In nutrient-limited batch cultures that received N and P enrichment, the N-enriched cultures showed a more diverse toxin profile than the P-enriched cells; the toxin content of N-enriched cells was lower than in the P-enriched cultures. We infer the following order for the biosynthesis of individual toxins: C1, C2>GTX3>GTX1>neoSTX. PMID- 26874748 TI - Linkage between speciation of Cd in mangrove sediment and its bioaccumulation in total soft tissue of oyster from the west coast of India. AB - This study established a mechanistic linkage between Cd speciation and bioavailability in mangrove system from the west coast of India. High bioaccumulation of Cd was found in the oyster (Crassostrea sp.) even at low Cd loading in the bottom sediment. Bioaccumulation of Cd in the oyster gradually increased with the increasing concentrations of water soluble, exchangeable and carbonate/bicarbonate forms of Cd in the sediments. Fe/Mn oxyhydroxide phase was found to control Cd bioavailability in the sediment system. Cd-associated with sedimentary organic matter was bioavailable and organic ligands in the sediments were poor chelating agents for Cd. This study suggests that bioaccumulation of Cd in oyster (Crassostrea sp.) depends not on the total Cd concentration but on the speciation of Cd in the system. PMID- 26874749 TI - Baseline trace elements in the seagrass Halodule wrightii Aschers (Cymodoceaceae) from Todos os Santos Bay, Bahia, Brazil. AB - Trace elements concentrations (As, Ba, Cd, Cr, Cu, Ni, Pb, V and Zn) were found in samples of Halodule wrightii Aschers (Cymodoceaceae) seagrass from Todos os Santos Bay, Bahia, Brazil by inductively coupled plasma mass spectrometry (ICP MS). This bay has been impacted by the presence of industrial activity that includes chemical and petrochemical plants as well as an oil refinery and harbor activities located in the north and northeastern area. Samples were collected at 4 stations to evaluate the distribution of element concentrations in this area and under different climatic conditions. The mean concentrations, in mgkg(-1), found in dry tissues for all the studied metals and stations were: As (1.08 5.42), Ba (3.72-32.0), Cd (0.135-1.68), Cr (1.15-10.4), Cu (2.23-13.4), Ni (1.95 9.87), Pb (0.873-5.18), V (3.39-22.4) and Zn (13.1-39.5). Statistical analysis (ANOVA) of the seagrass data showed significant inter-site differences for all elements examined except nickel and vanadium. PMID- 26874750 TI - Self-control over combined video feedback and modeling facilitates motor learning. AB - Allowing learners to control the video presentation of knowledge of performance (KP) or an expert model during practice has been shown to facilitate motor learning (Aiken, Fairbrother, & Post, 2012; Wulf, Raupach, & Pfeiffer, 2005). Split-screen replay features now allow for the simultaneous presentation of these modes of instructional support. It is uncertain, however, if such a combination incorporated into a self-control protocol would yield similar benefits seen in earlier self-control studies. Therefore, the purpose of the present study was to examine the effects of self-controlled split-screen replay on the learning of a golf chip shot. Participants completed 60 practice trials, three administrations of the Intrinsic Motivation Inventory, and a questionnaire on day one. Retention and transfer tests and a final motivation inventory were completed on day two. Results revealed significantly higher form and accuracy scores for the self control group during transfer. The self-control group also had significantly higher scores on the perceived competence subscale, reported requesting feedback mostly after perceived poor trials, and recalled a greater number of critical task features compared to the yoked group. The findings for the performance measures were consistent with previous self-control research. PMID- 26874751 TI - Learning to modulate the partial powers of a single sEMG power spectrum through a novel human-computer interface. AB - New human-computer interfaces that use bioelectrical signals as input are allowing study of the flexibility of the human neuromuscular system. We have developed a myoelectric human-computer interface which enables users to navigate a cursor to targets through manipulations of partial powers within a single surface electromyography (sEMG) signal. Users obtain two-dimensional control through simultaneous adjustments of powers in two frequency bands within the sEMG spectrum, creating power profiles corresponding to cursor positions. It is unlikely that these types of bioelectrical manipulations are required during routine muscle contractions. Here, we formally establish the neuromuscular ability to voluntarily modulate single-site sEMG power profiles in a group of naive subjects under restricted and controlled conditions using a wrist muscle. All subjects used the same pre-selected frequency bands for control and underwent the same training, allowing a description of the average learning progress throughout eight sessions. We show that subjects steadily increased target hit rates from 48% to 71% and exhibited greater control of the cursor's trajectories following practice. Our results point towards an adaptable neuromuscular skill, which may allow humans to utilize single muscle sites as limited general-purpose signal generators. Ultimately, the goal is to translate this neuromuscular ability to practical interfaces for the disabled by using a spared muscle to control external machines. PMID- 26874752 TI - Activation of microglia within paraventricular nucleus of hypothalamus is NOT involved in maintenance of established hypertension. AB - BACKGROUND: Inflammation within paraventricular nucleus of the hypothalamus (PVN), a key circulatory control center in the hypothalamus, is an important pathology of sympathetic hyperactivity. Brain inflammation is mainly mediated by microglia, innate immune cells in the brain. Activated microglia produce inflammatory cytokines with alteration of their morphology. Increase in inflammatory cytokines synthesis coincides with activation of microglia within PVN of angiotensin II-induced hypertensive model and myocardial infarction induced heart failure model. Although the increase in inflammatory cytokines and the microglial activation within PVN were also seen in spontaneously hypertensive rats (SHR), the model of essential hypertension, their involvement in blood pressure regulation has still be fully clarified. In the present study, we examined whether activated microglia within PVN were involved in maintenance of established severe hypertension with sympathoexcitation. METHODS: Minocycline (25mg/kg/day), an inhibitor of microglial activation, or vehicle were orally administered to stroke-prone SHR (SHRSP) and normotensive Wistar-Kyoto (WKY) rats for 2 weeks from 15-weeks-old, the age of established hypertension. RESULTS: Systolic blood pressure was comparable between minocycline treated-SHRSP and vehicle treated-SHRSP, whereas morphological analysis of microglia revealed smaller cell size in minocycline treated-SHRSP than vehicle treated-SHRSP, implying that minocycline deactivated microglia within PVN. CONCLUSIONS: Activated microglia with morphological alteration within PVN are not involved in the maintenance of established severe hypertension, and inflammation within PVN could not be the therapeutic target of established hypertension. PMID- 26874753 TI - Simple interventions to improve healthy eating behaviors in the school cafeteria. AB - The National School Lunch Program in the United States provides an important opportunity to improve nutrition for the 30 million children who participate every school day. The purpose of this narrative review is to present and evaluate simple, evidence-based strategies to improve healthy eating behaviors at school. Healthy eating behaviors are defined as increased selection/consumption of fruits and/or vegetables, increased selection of nutrient-dense foods, or decreased selection of low-nutrient, energy-dense foods. Data were collected from sales records, 24-hour food recalls, direct observation, and estimation of plate waste. The review is limited to simple, discrete interventions that are easy to implement. Sixteen original, peer-reviewed articles are included. Interventions are divided into 5 categories: modification of choice, behavior modification, marketing strategies, time-efficiency strategies, and fruit slicing. All interventions resulted in improved eating behaviors, but not all interventions are applicable or feasible in all settings. Because these studies were performed prior to the implementation of the new federally mandated school meal standards, it is unknown if these interventions would yield similar results if repeated now. PMID- 26874754 TI - The utility of two marine community indices to assess the environmental degradation of lotic systems using fish communities. AB - Multimetric approaches are commonly used to evaluate the ecological status of aquatic ecosystems. However, it has been recommended that the sensitivity of existing methods be improved through the investigation of the potential of new metrics to detect environmental disturbances. In this study we tested the effectiveness of two community indices (Taxonomic distinctness index (TDI) and Abundance biomass comparison (ABC) method), primarily proposed for marine ecosystems, to identify sites with different levels of environmental degradation in lotic systems using fish community data. Fish samples were collected over the period 2003-2011 at 131 sampling stations. To generate water and habitat quality classes, a self-organizing map (SOM) based on environmental data was applied. Gradients over the SOM map were investigated for the values of the TDI and ABC indices. The results of this study reveal that the values of both the TDI and ABC indices are highly correlated with water and habitat quality gradients. However, despite the observed correlation, the utility of TDI as a potential metric in bioassessment programs is rather limited, due to its lack of discriminatory power. In contrast, the ABC method could be proposed as a novel metric, but can only be applied in type-specific multimetric approaches. PMID- 26874755 TI - Sulfamethoxazole, tetracycline and oxytetracycline and related antibiotic resistance genes in a large-scale landfill, China. AB - Landfills are likely to be important reservoirs of antibiotics and antibiotic resistant genes (ARGs) as they receive unused and unwanted antibiotics and ARGs in municipal solid waste (MSW). The distribution, transportation and dynamics of antibiotics and ARGs in landfills remain largely unknown. In the present study, 3 antibiotics - sulfamethoxazole (SMX), tetracycline (TC), and oxytetracycline (OTC) - and their related ARGs (sulI and tetO) were quantified in 51 refuse samples from different depths at 8 locations within a large-scale landfill in central China. The average concentration of OTC was the highest, up to 100.9+/ 141.81MUg/kg (dw, n=48), followed by TC (63.8+/-37.7MUg/kg, n=40), and SMX (47.9+/-8.1MUg/kg, n=30). Both sulI and tetO were detected in all samples. Of the ARGs, sul1 (-3.06+/-1.18, n=51, log10 ARGs/16SrDNA) was more abundant than tetO ( 4.37+/-0.97) in all refuse samples (p<0.05). Both sulI and tetO negatively correlated to refuse age, suggesting they are attenuated during landfill stabilization. OTC and TC positively correlated to tetO (r=0.41, p<0.01) and sulI (r=0.29, p=0.04), respectively. Chemical conditions (e.g. moisture content and nitrate concentrations) within the refuse correlated to antibiotics and ARGs suggesting environmental factors impact the distribution of antibiotics and ARGs in landfill matrix. This study is the first comprehensive in situ landfill study to connect the concentrations of antibiotic residues to ARGs. PMID- 26874756 TI - Functional degradation of the water-sediment regulation scheme in the lower Yellow River: Spatial and temporal analyses. AB - Heavy sedimentation has led to the phenomenon of a secondary perched river in the lower reaches of the Yellow River. The water-sediment regulation scheme (WSRS) using the Xiaolangdi Reservoir was first implemented in 2002 to try to solve this problem. In this study, we analyzed the spatial and temporal effects of the current WSRS (2005-2013) on the lower Yellow River. Our results suggest that the current WSRS is exhibiting a tendency towards functional degradation, meaning that the scheme is no longer as effective as it was initially for the lower Yellow River. Although the main river channel has been fully scoured in the lower reaches since the implementation of the WSRS, we found that the degree of erosion declined gradually in a top-down fashion from the braided reach, through the transitional reach, to the meandering reach. Of the total eroded sediment, 69.64% came from the braided reach and only 6.61% came from the meandering reach. In addition, the reduction in riverbed elevation-a key function of the WSRS-has clearly slowed since 2005. We discuss the mechanisms underlying this functional degradation of the current WSRS and future challenges for the management of the lower Yellow River. Insights gained from this study will likely be of use to those weighing up options for future implementations of the WSRS. PMID- 26874757 TI - A batch assay to measure microbial hydrogen sulfide production from sulfur containing solid wastes. AB - Large volumes of sulfur-containing wastes enter municipal solid waste landfills each year. Under the anaerobic conditions that prevail in landfills, oxidized forms of sulfur, primarily sulfate, are converted to sulfide. Hydrogen sulfide (H2S) is corrosive to landfill gas collection and treatment systems, and its presence in landfill gas often necessitates the installation of expensive removal systems. For landfill operators to understand the cost of managing sulfur containing wastes, an estimate of the H2S production potential is needed. The objective of this study was to develop and demonstrate a biochemical sulfide potential (BSP) test to measure the amount of H2S produced by different types of sulfur-containing wastes in a relatively fast (30days) and inexpensive (125mL serum bottles) batch assay. This study confirmed the toxic effect of H2S on both sulfate reduction and methane production in batch systems, and demonstrated that removing accumulated H2S by base adsorption was effective for mitigating inhibition. H2S production potentials of coal combustion fly ash, flue gas desulfurization residual, municipal solid waste combustion ash, and construction and demolition waste were determined in BSP assays. After 30days of incubation, most of the sulfate in the wastes was converted to gaseous or aqueous phase sulfide, with BSPs ranging from 0.8 to 58.8mLH2S/g waste, depending on the chemical composition of the samples. Selected samples contained solid phase sulfide which contributed to the measured H2S yield. A 60day incubation in selected samples resulted in 39-86% additional sulfide production. H2S production measured in BSP assays was compared with that measured in simulated landfill reactors and that calculated from chemical analyses. H2S production in BSP assays and in reactors was lower than the stoichiometric values calculated from chemical composition for all wastes tested, demonstrating the importance of assays to estimate the microbial sulfide production potential of sulfur-containing wastes. PMID- 26874758 TI - Screening for diets that reduce urinary nitrogen excretion and methane emissions while maintaining or increasing production by dairy cows. AB - Farmers face complex decisions at the time to feed animals, trying to achieve production goals while contemplating social and environmental constraints. Our purpose was to facilitate such decision making for pastoral dairy farmers, aiming to reduce urinary N (UN) and methane emissions (CH4), while maintaining or increasing milk production (MP). There is a number of feeds the farmers can choose from and combine. We used 50 feeds (forages and grains) combined systematically in different proportions producing 11,526 binary diets. Diets were screened, using an a posteriori approach and a Pareto front (PF) analysis of model (Molly) outputs. The objective was to identify combinations with the best possible compromise (i.e. frontier) between UN, CH4, and MP. Using high MP and low UN as objective functions, PF included 10, 14, 12 and 50 diets, for non lactating, early-, mid- and late-lactation periods, with cereals and beets featuring strongly. Using the same objective functions, but including ryegrass as dietary base PF included 2, 4, 8 and 4 diets for those periods. Therefore, from a wide range of diets, farmers could choose from few feeds combined into binary diets to reduce UN while maintaining or increasing MP. If the intention is maintaining pasture-based systems, there are fewer suitable options. Reducing UN will simply require dilution of N supplied by pasture by supplementing low N conserved forages. The results also evidence the risk of pollution swapping, reaching the frontier means arriving at a point where trade-off decisions need to be made. Any further reduction in UN implies an increment in CH4, or reduction in CH4 emissions increases UN. There is no perfect diet to optimize all objectives simultaneously; but if the current diet is not in the frontier some options can offset pollution swapping. The choice is with the farmers and conditioned by their context. PMID- 26874759 TI - Operational and environmental determinants of in-vehicle CO and PM2.5 exposure. AB - This study presents a modeling framework to quantify the complex roles that traffic, seasonality, vehicle characteristics, ventilation, meteorology, and ambient air quality play in dictating in-vehicle commuter exposure to CO and PM2.5. For this purpose, a comprehensive one-year monitoring program of 25 different variables was coupled with a multivariate regression analysis to develop models to predict in-vehicle CO and PM2.5 exposure using a database of 119 mobile tests and 120 fume leakage tests. The study aims to improve the understanding of in-cabin exposure, as well as interior-exterior pollutant exchange. Model results highlighted the strong correlation between out-vehicle and in-vehicle concentrations, with the effect of ventilation type only discerned for PM2.5 levels. Car type, road conditions, as well as meteorological conditions all played a significant role in modulating in-vehicle exposure. The CO and PM2.5 exposure models were able to explain 72 and 92% of the variability in measured concentrations, respectively. Both models exhibited robustness and no-evidence of over-fitting. PMID- 26874760 TI - Radiative absorption enhancement from coatings on black carbon aerosols. AB - The radiative absorption enhancement of ambient black carbon (BC), by light refractive coatings of atmospheric aerosols, constitutes a large uncertainty in estimates of climate forcing. The direct measurements of radiative absorption enhancement require the experimentally-removing the coating materials in ambient BC-containing aerosols, which remains a challenge. Here, the absorption enhancement of the BC core by non-absorbing aerosol coatings was quantified using a two-step removal of both inorganic and organic matter coatings of ambient aerosols. The mass absorption cross-section (MAC) of decoated/pure atmospheric BC aerosols of 4.4+/-0.8m(2)g(-1) was enhanced to 9.6+/-1.8m(2)g(-1) at 678-nm wavelength for ambiently-coated BC aerosols at a rural Northern China site. The enhancement of MAC (EMAC) rises from 1.4+/-0.3 in fresh combustion emissions to ~3 for aged ambient China aerosols. The three-week high-intensity campaign observed an average EMAC of 2.25+/-0.55, and sulfates were primary drivers of the enhanced BC absorption. PMID- 26874761 TI - Impact of vineyard abandonment and natural recolonization on metal content and availability in Mediterranean soils. AB - Abandonment of vineyards after uprooting has dramatically increased in last decades in Mediterranean countries, often followed by vegetation expansion processes. Inadequate management strategies can have negative consequences on soil quality. We studied how the age and type of vegetation cover and several environmental characteristics (lithology, soil properties, vineyard slope and so on) after vineyard uprooting and abandonment contribute to the variation patterns in total, HAc (acetic acid-method, HAc) and EDTA-extractable (ethylenediaminetetraacetic acid-method) concentrations of Cd, Cu, Pb and Zn in soils. We sampled 141 points from vineyards and abandoned vineyard Mediterranean soils recolonized by natural vegetation in recent decades. The contribution of several environmental variables (e.g. age and type of vegetation cover, lithology, soil properties and vineyard slope) to the total and extractable concentrations of metals was evaluated by canonical ordination based on redundancy analysis, considering the interaction between both environmental and response variables. The ranges of total metal contents were: 0.01-0.15 (Cd), 2.6 34 (Cu), 6.6-30 (Pb), and 29-92mgkg(-1) (Zn). Cadmium (11-100%) had the highest relative extractability with both extractants, and Zn and Pb the lowest. The total and EDTA-extractable of Cd, Pb and Zn were positively related to the age of abandonment, to the presence of Agrostis castellana and Retama sphaerocarpa, and to the contents of Fe-oxides, clay and organic matter (OM). A different pattern was noted for Cu, positively related to vineyard soils. Soil properties successfully explained HAc-extractable Cd, Cu, Pb and Zn but the age and type of vegetation cover lost significance. Clay content was negatively related to HAc extractable Cu and Pb; and OM was positively related to HAc-Cd and Zn. In conclusion, the time elapsed after vineyard uprooting, and subsequent land abandonment, affects the soil content and availability of metals, and this impact depended on the colonizing plant species and soil properties. PMID- 26874762 TI - Acute exposure to fine and coarse particulate matter and infant mortality in Tokyo, Japan (2002-2013). AB - Few studies have evaluated the effect of short-term exposure to particulate matter (PM) less than 2.5MUm in diameter (PM2.5) or to coarse particles on infant mortality. We evaluated the association between short-term exposure to PM and infant mortality in Japan and assessed whether adverse health effects were observable at PM concentrations below Japanese air quality guidelines. We used a time-stratified, case-crossover design. The participants included 2086 infants who died in the 23 urbanized wards of the Tokyo Metropolitan Government between January 2002 and December 2013. We obtained measures of PM2.5 and suspended particulate matter (SPM; PM<7MUm in diameter) from one general monitoring station. As a measure of coarse particles, we calculated PM7-2.5 by subtracting PM2.5 from SPM. We then used conditional logistic regression to analyze the data. Same-day PM2.5 was associated with increased risks of infant and postneonatal mortality, especially for mortality related to respiratory causes. For a 10MUg/m(3) increase in PM2.5, the odds ratios were 1.06 (95% confidence interval: 1.01-1.12) for infant mortality and 1.10 (1.02-1.19) for postneonatal mortality. PM7-2.5 was also associated with an increased risk of postneonatal mortality, independent of PM2.5. Even when PM2.5 and SPM concentrations were below Japanese air quality guidelines, we observed adverse health effects. This study provides further evidence that acute exposure to PM2.5 and coarse particles (PM7-2.5) is associated with an increased risk of infant mortality. Further, rigorous evaluation of air quality guidelines for daily average PM2.5 and larger particles is needed. PMID- 26874763 TI - Modeling olive pollen intensity in the Mediterranean region through analysis of emission sources. AB - Aerobiological monitoring of Olea europaea L. is of great interest in the Mediterranean basin because olive pollen is one of the most represented pollen types of the airborne spectrum for the Mediterranean region, and olive pollen is considered one of the major cause of pollinosis in this region. The main aim of this study was to develop an airborne-pollen map based on the Pollen Index across a 4-year period (2008-2011), to provide a continuous geographic map for pollen intensity that will have practical applications from the agronomical and allergological points of view. For this purpose, the main predictor variable was an index based on the distribution and abundance of potential sources of pollen emission, including intrinsic information about the general atmospheric patterns of pollen dispersal. In addition, meteorological variables were included in the modeling, together with spatial interpolation, to allow the definition of a spatial model of the Pollen Index from the main olive cultivation areas in the Mediterranean region. The results show marked differences with respect to the dispersal patterns associated to the altitudinal gradient. The findings indicate that areas located at an altitude above 300ma.s.l. receive greater amounts of olive pollen from shorter-distance pollen sources (maximum influence, 27km) with respect to areas lower than 300ma.s.l. (maximum influence, 59km). PMID- 26874764 TI - Application of disease burden to quantitative assessment of health hazards for a decentralized water reuse system. AB - The aim of this article is to introduce the methodology of disease burden (DB) to quantify the health impact of microbial regrowth during wastewater reuse, using the case study of a decentralized water reuse system in Xi'an Si-yuan University, located in Xi'an, China. Based on field investigation findings, Escherichia coli (E. coli), Salmonella and rotavirus were selected as typical regrowth pathogens causing potential health hazards during the reuse of reclaimed water. Subsequently, major exposure routes including sprinkler irrigation, landscape fountains and toilet flushing were identified. Mathematical models were established to build the relationship between exposure dose and disease burden by calculating the disability adjusted life year (DALY). Results of disease burden for this case study show that DALYs attributed to E. coli were significantly greater than those caused by other pathogens, and DALYs associated with sprinkler irrigation were higher than those originating from other routes. A correlation between exposure dose and disease was obtained by introducing a modified calculation of morbidity, which can extend the assessment endpoint of health risk to disease burden from the conventional infection rate. PMID- 26874765 TI - Pan-Arctic concentrations of mercury and stable isotope ratios of carbon (delta(13)C) and nitrogen (delta(15)N) in marine zooplankton. AB - Zooplankton play a central role in marine food webs, dictating the quantity and quality of energy available to upper trophic levels. They act as "keystone" species in transfer of mercury (Hg) up through the marine food chain. Here, we present the first Pan-Arctic overview of total and monomethylmercury concentrations (THg and MMHg) and stable isotope ratios of carbon (delta(13)C) and nitrogen (delta(15)N) in selected zooplankton species by assembling data collected between 1998 and 2012 from six arctic regions (Laptev Sea, Chukchi Sea, southeastern Beaufort Sea, Canadian Arctic Archipelago, Hudson Bay and northern Baffin Bay). MMHg concentrations in Calanus spp., Themisto spp. and Paraeuchaeta spp. were found to increase with higher delta(15)N and lower delta(13)C. The southern Beaufort Sea exhibited both the highest THg and MMHg concentrations. Biomagnification of MMHg between Calanus spp. and two of its known predators, Themisto spp. and Paraeuchaeta spp., was greatest in the southern Beaufort Sea. Our results show large geographical variations in Hg concentrations and isotopic signatures for individual species related to regional ecosystem features, such as varying water masses and freshwater inputs, and highlight the increased exposure to Hg in the marine food chain of the southern Beaufort Sea. PMID- 26874766 TI - Monitoring of fluoride in water samples using a smartphone. AB - In several parts of India, groundwater is the only reliable, year round source for drinking water. Prevention of fluorosis, a chronic disease resulting from excess intake of fluoride, requires the screening of all groundwater sources for fluoride in endemic areas. In this paper, the authors present a field deployable colorimetric analyzer based on an inexpensive smartphone embedded with digital camera for taking photograph of the colored solution as well as an easy-fit, and compact sample chamber (Akvo Caddisfly). Phones marketed by different smartphone makers were used. Commercially available zirconium xylenol orange reagent was used for determining fluoride concentration. A software program was developed to use with the phone for recording and analyzing the RGB color of the picture. Linear range for fluoride estimation was 0-2mgl(-1). Around 200 samples, which consisted of laboratory prepared as well as field samples collected from different locations in Karnataka, India, were tested with Akvo Caddisfly. The results showed a significant positive correlation between Ion Selective Electrode (ISE) method and Akvo Caddisfly (Phones A, B and C), with correlation coefficient ranging between 0.9952 and 1.000. In addition, there was no significant difference in the mean fluoride content values between ISE and Phone B and C except for Phone A. Thus the smartphone method is economical and suited for groundwater fluoride analysis in the field. PMID- 26874767 TI - Influence of climatic and hydrological factors on structure and composition of peat from northern wetland territories with low anthropogenic impact. AB - Northern wetlands ecosystems play an important role in the hydrological balance of neighboring areas, where they act as chemical barriers against anthropogenic and technogenic contaminations. Studied region is well known for quantity of peat deposits and the volume of peat resources. Peat can be considered as a highly informative marker for assessing change in environmental conditions. The study presents the results of the first investigation of peat samples, collected from representative ecosystems of northern wetland territories with low anthropogenic impact. Component and element composition of various peat types were studied in a relation to hydrologic, climate and sampling conditions. It was found out that organic and ash contents are more dependent on the type of the bog, than geographic location. Climatic factors are more important for the formation of bitumen. The degradation degree in peat increases proportionally to content of humates. High content of biogenic and lithogenic elements was observed in transition- and low-moor peat. The content of trace elements in peat samples do not depend on the type of the peat. The structural properties of peat were studied by the light microscopy, AFM and dynamic light scattering. It was determined that the conformation of studied peat samples is characterized by elements of asymmetry. The observed particles in the solutions exist in dynamic equilibrium with separated globular macromolecules. The size of these nanoparticles is comparable with the size of the particles of other biopolymers of similar nature. Swelling of peat in liquid water was studied. The relationship between structural specificities, origin of peat and its maximum degree of swelling was found. The degree of swelling can be used as structural-sensitive parameter in further research. PMID- 26874768 TI - Organic nitrogen storage in mineral soil: Implications for policy and management. AB - Nitrogen is one of the most important ecosystem nutrients and often its availability limits net primary production as well as stabilization of soil organic matter. The long-term storage of nitrogen-containing organic matter in soils was classically attributed to chemical complexity of plant and microbial residues that retarded microbial degradation. Recent advances have revised this framework, with the understanding that persistent soil organic matter consists largely of chemically labile, microbially processed organic compounds. Chemical bonding to minerals and physical protection in aggregates are more important to long-term (i.e., centuries to millennia) preservation of these organic compounds that contain the bulk of soil nitrogen rather than molecular complexity, with the exception of nitrogen in pyrogenic organic matter. This review examines for the first time the factors and mechanisms at each stage of movement into long-term storage that influence the sequestration of organic nitrogen in the mineral soil of natural temperate ecosystems. Because the factors which govern persistence are different under this newly accepted paradigm we examine the policy and management implications that are altered, such as critical load considerations, nitrogen saturation and mitigation consequences. Finally, it emphasizes how essential it is for this important but underappreciated pool to be better quantified and incorporated into policy and management decisions, especially given the lack of evidence for many soils having a finite capacity to sequester nitrogen. PMID- 26874769 TI - Is digestate safe? A study on its ecotoxicity and environmental risk on a pig manure. AB - Digestate represents a precious by-product in particular in agriculture, however its impact on the environment and human health is still unexplored. In this work, the toxicity of a pig slurry digestate was assessed through 7 ecotoxicity tests and considering 10 different endpoints. Besides, a synthetic index was applied to the outputs of the battery of tests for the environmental risk assessment, in order to evaluate the opportunity to use directly this kind of digestate in agriculture or to introduce an additional treatment. All the organisms were sensitive to digestate toxicity (EC50 ranged from 14.22% for Cucumissativus to 0.77% for Raphidocelis subcapitata). The physical-chemical features at the base of this toxicity seem to be the high content of ammonium, salinity, COD, phosphate and colour. The synthetic index showed that the digestate was very toxic and associated to an extremely high environmental risk. Thus, a pre treatment is needed to reduce its toxicity and environmental impact, whatever could be its exploitation. PMID- 26874770 TI - Differences in dissolved organic matter between reclaimed water source and drinking water source. AB - Dissolved organic matter (DOM) significantly affects the quality of reclaimed water and drinking water. Reclaimed water potable reuse is an effective way to augment drinking water source and de facto reuse exists worldwide. Hence, when reclaimed water source (namely secondary effluent) is blended with drinking water source, understanding the difference in DOM between drinking water source (dDOM) and reclaimed water source (rDOM) is essential. In this study, composition, transformation, and potential risk of dDOM from drinking water source and rDOM from secondary effluent were compared. Generally, the DOC concentration of rDOM and dissolved organic nitrogen (DON) content in reclaimed water source were higher but rDOM exhibited a lower aromaticity. Besides, rDOM comprises a higher proportion of hydrophilic fractions and more low-molecular weight compounds, which are difficult to be removed during coagulation. Although dDOM exhibited higher specific disinfection byproducts formation potential (SDBPFP), rDOM formed more total disinfection byproducts (DBPs) during chlorination including halomethanes (THMs) and haloacetic acids (HAAs) due to high DOC concentration. Likewise, in consideration of DOC basis, rDOM contained more absolute assimilable organic carbon (AOC) despite showing a lower specific AOC (normalized AOC per unit of DOC). Besides, rDOM exhibited higher biotoxicity including genotoxicity and endocrine disruption. Therefore, rDOM presents a greater potential risk than dDOM does. Reclaimed water source needs to be treated carefully when it is blended with drinking water source. PMID- 26874771 TI - Radioactive Cs in the estuary sediments near Fukushima Daiichi Nuclear Power Plant. AB - The migration and dispersion of radioactive Cs (mainly (134)Cs and (137)Cs) are of critical concern in the area surrounding the Fukushima Daiichi Nuclear Power Plant (FDNPP). Considerable uncertainty remains in understanding the properties and dynamics of radioactive Cs transport by surface water, particularly during rainfall-induced flood events to the ocean. Physical and chemical properties of unique estuary sediments, collected from the Kuma River, 4.0km south of the FDNPP, were quantified in this study. These were deposited after storm events and now occur as dried platy sediments on beach sand. The platy sediments exhibit median particle sizes ranging from 28 to 32MUm. There is increasing radioactivity towards the bottom of the layers deposited; approximately 28 and 38Bqg(-1) in the upper and lower layers, respectively. The difference in the radioactivity is attributed to a larger number of particles associated with radioactive Cs in the lower part of the section, suggesting that radioactive Cs in the suspended soils transported by surface water has decreased over time. Sequential chemical extractions showed that ~90% of (137)Cs was strongly bound to the residual fraction in the estuary samples, whereas 60~80% of (137)Cs was bound to clays in the six paddy soils. This high concentration in the residual fraction facilitates ease of transport of clay and silt size particles through the river system. Estuary sediments consist of particles <100MUm. Radioactive Cs desorption experiments using the estuary samples in artificial seawater revealed that 3.4+/ 0.6% of (137)Cs was desorbed within 8h. More than 96% of (137)Cs remained strongly bound to clays. Hence, particle size is a key factor that determines the travel time and distance during the dispersion of (137)Cs in the ocean. PMID- 26874772 TI - Urban surface water pollution problems arising from misconnections. AB - The impacts of misconnections on the organic and nutrient loadings to surface waters are assessed using specific household appliance data for two urban sub catchments located in the London metropolitan region and the city of Swansea. Potential loadings of biochemical oxygen demand (BOD), soluble reactive phosphorus (PO4-P) and ammoniacal nitrogen (NH4-N) due to misconnections are calculated for three different scenarios based on the measured daily flows from specific appliances and either measured daily pollutant concentrations or average pollutant concentrations for relevant greywater and black water sources obtained from an extensive review of the literature. Downstream receiving water concentrations, together with the associated uncertainties, are predicted from derived misconnection discharge concentrations and compared to existing freshwater standards for comparable river types. Consideration of dilution ratios indicates that these would need to be of the order of 50-100:1 to maintain high water quality with respect to BOD and NH4-N following typical misconnection discharges but only poor quality for PO4-P is likely to be achievable. The main pollutant loading contributions to misconnections arise from toilets (NH4-N and BOD), kitchen sinks (BOD and PO4-P) washing machines (PO4-P and BOD) and, to a lesser extent, dishwashers (PO4-P). By completely eliminating toilet misconnections and ensuring misconnections from all other appliances do not exceed 2%, the potential pollution problems due to BOD and NH4-N discharges would be alleviated but this would not be the case for PO4-P. In the event of a treatment option being preferred to solve the misconnection problem, it is shown that for an area the size of metropolitan Greater London, a sewage treatment plant with a Population Equivalent value approaching 900,000 would be required to efficiently remove BOD and NH4-N to safely dischargeable levels but such a plant is unlikely to have the capacity to deal satisfactorily with incoming PO4-P loads from misconnections. PMID- 26874773 TI - On the relationship between sea surface temperatures, circulation parameters and temperatures over west coast of India. AB - The oceans and the atmosphere are tightly linked and they together form the most dynamic component of the climate system. Topography and proximity to the surrounding seas of the region determine the temperature of the area. West Coast (WC) of India is a high elevated region surrounded by large oceanic area, therefore, an attempt is made in this study to examine the trends and variability in temperature over WC in relation to oceanic phenomena. Temperature over the WC shows considerable year-to-year variation with anomalous cool years in recent warm epoch. Therefore, sea surface temperature (SST) and associated winds have been analyzed to understand possible mechanism behind the variation in temperatures over the WC. During the winter, north-easterlies prevail over the WC which blows from land to ocean. Variations in SSTs alter the strength of these winds to cause anomalies in temperature over the WC. Indian Ocean Dipole (IOD) appears to have a dominant role in climate of the WC, whereas SSTs over the equatorial Pacific do not show any impact on temperatures over the WC. Study indicates that the strengthening of north-easterlies due to negative phase of Indian Ocean Dipole causes cooling over the WC of India. PMID- 26874774 TI - Monitoring priority substances, other organic contaminants and heavy metals in a volcanic aquifer from different sources and hydrological processes. AB - Irrigation with reclaimed water (R) is necessary to guarantee the sustainability of semi-arid areas. Results obtained during a two years monitoring network (2009 2011) in Gran Canaria are presented, including the analysis of chemical parameters, N and S isotopes, priority substances (2008/105/EC, 2013/39/EU), other organic contaminants and heavy metals in groundwater and R used to irrigate a golf course. The aims of this work are to evaluate the contamination in a volcanic aquifer, relate the presence of organic contaminants and heavy metals with the hydrogeochemistry and identify pollution sources in the area. No priority substance exceeded the EU thresholds for surface water, although seventeen were detected in R. The most frequent compounds were hexachlorobenzene, chlorpyrifos ethyl, fluorene, phenanthrene and pyrene. These compounds were detected at low concentration, except chlorpyrifos. Chlorpyrifos ethyl, terbuthylazine, diuron, terbutryn, procymidone, atrazine and propazine exceeded the European threshold concentration for pesticides in groundwater (100ngL(-1)). Therefore, the priority substances chlorpyrifos ethyl and diuron must be included in monitoring studies. The priority pesticides chlorfenvinphos and diazinon were always detected in R but rarely in groundwater. Besides, the existence of contaminants not related to the current R irrigation has been identified. Absence of environmental problems related to heavy metals can be expected. The relationship among contaminant presence, hydrogeochemistry, including the stable isotopic prints of delta(18)O, delta(15)N and delta(34)S and preferential recharge paths has been described. The coastal well shows high values of EC, nitrate, a variable chemistry, and 50% of organic contaminants detected above 100ngL(-1). The well located in the recharge area presents a stable hydrochemistry, the lowest value of delta(15)N and the lowest contaminants occurrence. The area is an example of a complex volcanic media with several sources of contaminants such as leakages from septic tanks and sewerage, agriculture practices, irrigation with reclaimed water or urban runoff. PMID- 26874775 TI - NO and N2O emissions from agricultural fields in the North China Plain: Origination and mitigation. AB - Agricultural soil has been recognized as a major source of atmospheric NO and N2O emissions which have important impacts on regional and global environments. Here we comparably investigated the effects of ammonium, nitrate fertilizers and nitrification inhibitor dicyandiamide (DCD) addition on NO and N2O emissions from the agricultural soil in the North China Plain (NCP). Compared with the ammonium fertilizer application, the reductions of NO emissions caused by nitrate fertilizer and DCD addition were 100% and 93%, and of N2O emissions were 54% and 74%, respectively. Remarkable reductions of NO and N2O emissions were also observed from five different agricultural soils in the NCP by replacing ammonium with nitrate fertilizer, indicating that nitrification is the predominant process for the emissions of NO and N2O from the soils in the vast area of NCP. NO emission peaks were found to be several days later than N2O peaks after the application of ammonium fertilizer and flooding irrigation, implying that most of NO initially produced via nitrification process might be fast reduced to N2O under the high soil moisture condition. Interestingly, the relative contribution of denitrification to N2O emission showed obviously time-dependent, e.g., evident N2O emission caused by the application of nitrate was only observed after the basal fertilization for the maize and the topdressing for the wheat. Replacing ammonium with nitrate fertilizer and mixing with the nitrification inhibitor are verified to be effective measures for mitigating NO and N2O emissions from arable soils in the NCP. PMID- 26874776 TI - Management of toxicities of immune checkpoint inhibitors. AB - Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided. PMID- 26874777 TI - Temporal dynamics of norovirus determined through monitoring of municipal wastewater by pyrosequencing and virological surveillance of gastroenteritis cases. AB - Norovirus is a leading etiological agent of viral gastroenteritis. Because of relatively mild disease symptoms and frequent asymptomatic infections, information on the ecology of this virus is limited. Our objective was to examine the genetic diversity of norovirus circulating in the human population by means of genotyping the virus in municipal wastewater. We investigated norovirus genogroups I and II (GI and GII) in municipal wastewater in Japan by pyrosequencing and quantitative PCR (qPCR) from November 2012 to March 2013. Virological surveillance for gastroenteritis cases was concurrently conducted in the same area. A total of fourteen distinct genotypes in total (GI.1, 3, 4, 6, 7, GII.2, 4, 5, 6, 7, 12, 13, 14, and 17), with up to eight genotypes detected per sample, were observed in wastewater using pyrosequencing; only four genotypes (GI.6, GII.4, 5, and 14) were obtained from clinical samples. Seventy-eight percent of norovirus-positive stool samples contained GII.4, but this genotype was not dominant in wastewater. The norovirus GII.4 Sydney 2012 variant, which appeared and spread during our study period, was detected in both the wastewater and clinical samples. These results suggest that an environmental approach using pyrosequencing yields a more detailed distribution of norovirus genotypes/variants. Thus, wastewater monitoring by pyrosequencing is expected to provide an effective analysis of the distribution of norovirus genotypes causing symptomatic and asymptomatic infections in human populations. PMID- 26874778 TI - Nitrification inhibition by hexavalent chromium Cr(VI)--Microbial ecology, gene expression and off-gas emissions. AB - The goal of this study was to investigate the responses in the physiology, microbial ecology and gene expression of nitrifying bacteria to imposition of and recovery from Cr(VI) loading in a lab-scale nitrification bioreactor. Exposure to Cr(VI) in the reactor strongly inhibited nitrification performance resulting in a parallel decrease in nitrate production and ammonia consumption. Cr(VI) exposure also led to an overall decrease in total bacterial concentrations in the reactor. However, the fraction of ammonia oxidizing bacteria (AOB) decreased to a greater extent than the fraction of nitrite oxidizing bacteria (NOB). In terms of functional gene expression, a rapid decrease in the transcript concentrations of amoA gene coding for ammonia oxidation in AOB was observed in response to the Cr(VI) shock. In contrast, transcript concentrations of the nxrA gene coding for nitrite oxidation in NOB were relatively unchanged compared to Cr(VI) pre exposure levels. Therefore, Cr(VI) exposure selectively and directly inhibited activity of AOB, which indirectly resulted in substrate (nitrite) limitation to NOB. Significantly, trends in amoA expression preceded performance trends both during imposition of and recovery from inhibition. During recovery from the Cr(VI) shock, the high ammonia concentrations in the bioreactor resulted in an irreversible shift towards AOB populations, which are expected to be more competitive in high ammonia environments. An inadvertent impact during recovery was increased emission of nitrous oxide (N2O) and nitric oxide (NO), consistent with recent findings linking AOB activity and the production of these gases. Therefore, Cr(VI) exposure elicited multiple responses on the microbial ecology, gene expression and both aqueous and gaseous nitrogenous conversion in a nitrification process. A complementary interrogation of these multiple responses facilitated an understanding of both direct and indirect inhibitory impacts on nitrification. PMID- 26874779 TI - Analysis and assessment of the nutrients, biochemical indexes and heavy metals in the Three Gorges Reservoir, China, from 2008 to 2013. AB - The Three Gorges Reservoir, the world's largest hydropower project, has operated stably for more than five years. To understand its water quality status, the nutrient and biochemical indexes, the total nitrogen (TN), the total phosphorus (TP), the potassium permanganate index (CODMn), the five-day biochemical oxygen demand (BOD5) and fecal coliform (F. coli), as well as the heavy metals (Cu, Hg, As, Cd, Zn and Pb) of samples collected from 10 sites during the time period of 2008-2013 were studied via using multiple analysis approaches. For each parameter, pictures of the spatial and temporal distributions were presented, and the reasons behind their variation trends were elaborated. Principal component analysis (PCA) was applied to identify the types of pollution. The Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI) was calculated to concisely mark the water quality. In addition, a human health risk assessment of the heavy metals in a representative site was conducted. The results showed that the water quality state in the Three Gorges Reservoir was intricate but stable and acceptable from 2008 to 2013. The TN, TP and Pb were considered to be the key pollution indexes. Enforcements to alleviate industrial and urban pollution, along with ship management, have worked. The decrease in heavy metal concentrations from upstream to downstream was associated with the self-purification of the reservoir. However, rural pollution became worse in those years. Improper agricultural activity was an important reason for this trend. For local residents, drinking water was generally safe, but cancer caused by As and Pb is a potential issue. PMID- 26874780 TI - On the genetic bias of the quarter of birth instrument. AB - Many studies in economics use quarter of birth as an instrument for identifying the causal effect of schooling on outcomes such as earnings and health. The key assumption in these studies is that people born in different quarters of the year do not differ systematically in their unobserved abilities. This study uses genetic data from the US Health and Retirement Study to analyze the validity of the quarter of birth instrument. We find some evidence that genetic factors influencing education are not randomly distributed over the year. However, these factors only slightly change the effect of quarter of birth on schooling. PMID- 26874781 TI - Applying geographical information systems (GIS) to arboviral disease surveillance and control: A powerful tool. PMID- 26874783 TI - Video gaming and gender differences in digital and printed reading performance among 15-year-olds students in 26 countries. AB - Video games are a favorite leisure-time activity among teenagers worldwide. This study examines cross-national gender differences in reading achievement and video gaming and whether video gaming explains gender differences in reading achievement and differences in performance between paper-based and computer-based reading. We use data from a representative sample of 145,953 students from 26 countries who sat the PISA 2012 assessments and provided self-reports on use of video games. Although boys tend to have poorer results in both the computer-based and the paper-based reading assessments, boys' under achievement is smaller when the assessment is delivered on computer than when it is delivered on paper. Boys underperformance compared to girls in the two reading assessments is particularly pronounced among low-achieving students. Among both boys and girls moderate use of single-player games is associated with a performance advantage. However, frequent engagement with collaborative online games is generally associated with a steep reduction in achievement, particularly in the paper-based test and particularly among low-achieving students. Excessive gaming may hinder academic achievement, but moderate gaming can promote positive student outcomes. In many countries video gaming explains the difference in the gender gap in reading between the paper-based and the computer-based assessments. PMID- 26874782 TI - Nephrotic-range proteinuria in an eight-year-old traveler with severe dengue: Case report and review of the literature. AB - We report a case of an eight-year-old male, native of the Dominican Republic, who visited the U.S. and was admitted to a pediatric intensive care unit with severe dengue. He needed aggressive fluid management for dengue shock syndrome and developed proteinuria on the sixth day of his illness, shortly after his nadir thrombocytopenia. His proteinuria peaked on the eight day, and reduced to trace levels by the tenth day of his illness, coinciding with normalization of his platelet count. His highest random urine protein/creatinine ratio was in the nephrotic range, at 3.9 g/g. Dengue fever can cause a wide spectrum of acute kidney injury (AKI), ranging in incidence from 0.9 to 36%. Review of the literature shows that nephrotic-range proteinuria is an uncommon complication of AKI caused by dengue, reported thus far only in Southeast Asia. Immune-mediated mechanisms may explain the observed association between dengue-induced thrombocytopenia and severe proteinuria, in this case, and previously reported cases. Dengue virus infection is the commonest mosquito-borne disease in the world with substantial morbidity and mortality. Well-designed prospective studies are needed to further characterize the extent and mechanisms of AKI in populations living in countries with ongoing transmission, as well as in those with travel-associated disease. PMID- 26874784 TI - Mutual long-term effects of school bullying, victimization, and justice sensitivity in adolescents. AB - In the present study, we investigate long-term relations between experiences of aggression at school and the development of justice sensitivity as a personality disposition in adolescents. We assessed justice sensitivity (from the victim, observer, and perpetrator perspective), bullying, and victimization among 565 German 12- to 18-year-olds in a one-year longitudinal study with two measurement points. Latent path analyses revealed gender differences in long-term effects of bullying and victimization on observer sensitivity and victim sensitivity. Experiences of victimization at T1 predicted an increase in victim sensitivity among girls and a decrease in victim sensitivity among boys. Bullying behavior at T1 predicted an increase in victim sensitivity among boys and a decrease in observer sensitivity among girls. We did not find long-term effects of justice sensitivity on bullying and victimization. Our findings indicate that experiences of bullying and victimization have gender-specific influences on the development of moral personality dispositions in adolescents. PMID- 26874785 TI - The Relationship of Fluid Overload as Assessed by Bioelectrical Impedance Analysis with Pulmonary Arterial Hypertension in Hemodialysis Patients. AB - BACKGROUND Pulmonary arterial hypertension (PAH) is common disease among hemodialysis (HD) patients and is associated with increased morbidity and mortality. However, its pathogenesis has not been completely elucidated. We aimed to evaluate the frequency of PAH in HD patients, as well as the relationship between fluid status and PAH. MATERIAL AND METHODS We enrolled 77 HD patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status. BIA was performed before and 30 min after the midweek of HD. Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW >=7%. Echocardiographic examinations were performed before and after the HD. Pulmonary arterial hypertension was defined as systolic pulmonary artery pressure at rest (sPAP) higher than 35 mmHg. RESULTS PAH was found in 33.7% of the HD patients. OH/ECW and the frequency of fluid overload were significantly higher in HD patients with PAH than those without PAH, whereas serum albumin and hemoglobin levels were significantly lower. sPAP level was significantly higher in HD patients with fluid overload than in those without fluid overload after hemodialysis session. Furthermore, sPAP, OH/ECW levels, and the frequency of PAH were significantly reduced after HD. We also found a significant positive correlation between sPAP and OH/ECW. Multivariate logistic regression analysis demonstrated fluid overload to be an independent predictor of PAH after HD. CONCLUSIONS PAH is prevalent among HD patients. This study demonstrated a strong relationship between fluid overload and PAH in HD patients. PMID- 26874786 TI - Identification of Patient Characteristics Influencing Setting of Care Decisions for Patients With Acute Bacterial Skin and Skin Structure Infections: Results of a Discrete Choice Experiment. AB - PURPOSE: Rates of acute bacterial skin and skin structure infections (ABSSSI) have sharply increased since 2000. Treatment may be administered in the inpatient or outpatient setting; clinical decision-making regarding hospitalization is inconsistent, often leading to hospitalization of some patients with ABSSSI who qualify for outpatient parenteral antimicrobial therapy, which leads to increased overall care costs. New antibiotics such as oritavancin are hypothesized to be a cost-effective option improving accessibility to ambulatory treatment of ABSSSI. The goal of this study was to understand the patient attributes that affect clinical decision-making regarding the setting of care for ABSSSI treatment. METHODS: An observational, cross-sectional study was conducted that surveyed clinicians of various specialties from the United States and the United Kingdom. The survey collected quantitative responses and used a series of choice-based experimental designs to evaluate patient attributes influencing clinical treatment decisions. FINDINGS: Infection severity, severe comorbidities, and age >= 75 years were observed to have the greatest impact on treatment location decisions (odds ratio [OR], 0.000-0.004 [95% CI, 0.000-0.011], vs mild ABSSSI; OR, 0.246-0.484 [95% CI, 0.154-0.788], vs no active comorbidities; OR, 0.136 0.523 [95% CI, 0.070-0.888], vs <= 18 years, respectively). The majority of respondents indicated they would consider oritavancin to avoid postdischarge outpatient parenteral antimicrobial therapy or oral therapy, regardless of the pathogen (63.5%-83.5%). IMPLICATIONS: Key factors influencing ABSSSI treatment setting were severity of infection, severity of comorbidities, and age. Clinicians surveyed identified patient profiles in which single-dose oritavancin might enable wholly outpatient or shortened inpatient management. Additional studies to elucidate the ABSSSI care pathways that include oritavancin and other novel antibiotics are needed. PMID- 26874787 TI - Seasonal Patterns of Medications for Treating Attention-Deficit/Hyperactivity Disorder: Comparison of Methylphenidate and Atomoxetine. AB - PURPOSE: Medication is a first-line effective treatment for attention deficit/hyperactivity disorder (ADHD). Currently, immediate-release methylphenidate (IR-MPH), the osmotic, controlled-release formulation of methylphenidate (OROS-MPH), and atomoxetine (ATX) are the only 3 medications approved in Taiwan for the treatment of ADHD. Short-term discontinuation of ADHD treatment is often seen among patients undergoing drug therapy. The goal of this study was to evaluate potential seasonal patterns in ADHD prescriptions and compare the seasonal changes of IR-MPH, OROS-MPH, and ATX use. METHODS: Taiwan's National Health Insurance database was used to gather information on patients diagnosed with ADHD (N = 145,269) from January 2000 to December 2011. The monthly data regarding person-days and receipt of treatment with IR-MPH, OROS-MPH, and ATX were analyzed. Time series analyses and autoregressive integrated moving average models were used to examine the seasonal patterns in person-days receiving ADHD pharmacotherapy. A general linear model with a post hoc test was used to determine the differences in monthly consumption of ADHD medications. FINDINGS: This study comprised 145,269 patients (mean age: 7.7 years; 78.6% were boys) diagnosed with ADHD. The prescriptions of IR-MPH (seasonal autoregressive: estimate [SE], 0.92 [0.04], t = 22.87, P < 0.001) and OROS-MPH (estimate [SE], 0.84 [0.09], t = 9.41, P < 0.001) both showed significant seasonal patterns, but ATX prescriptions did not (estimate [SE], 0.50 [0.55]; t = 0.90; P = 0.373). IR MPH and OROS-MPH prescriptions shared similar seasonal trends. The mean person days of consumption in July were lower than in other months, with the exception of February and August. Meanwhile, for ATX, the person-days of consumption in February were the lowest. The mean person-days in February were significantly lower than in March and May but did not differ from those in other months. IMPLICATIONS: The seasonal patterns of IR-MPH and OROS-MPH use coincide with school holidays. These findings suggest that discontinuing a drug during the holiday period may be popular for people undergoing ADHD pharmacotherapy, especially with regard to methylphenidate prescriptions. However, additional research is necessary to determine whether temporary discontinuation of drug therapy is related to patient outcomes. PMID- 26874788 TI - Prevalence of parasitic infections and associations with pregnancy complications and outcomes in northern Tanzania: a registry-based cross-sectional study. AB - BACKGROUND: Parasitic infection(s) during pregnancy have been associated with increased risk of pregnancy complications and adverse outcomes in low resource settings. However, little is known about their influence on pregnancy outcomes. This study aimed to determine the prevalence of parasitic infections and their association with pregnancy complications and adverse outcomes. METHODS: A retrospective cross-sectional study was conducted using maternally-linked data from Kilimanjaro Christian Medical Center (KCMC) medical birth registry. Birth records from all women who delivered singleton infants from 2000-2011 were utilized. We excluded multiple gestations and rural medical referral for various medical complications. A total of 30,797 births were evaluated. Data analysis was performed using SPSS version 18.0. Odds ratio (ORs) with 95 % confidence intervals (CIs) for adverse pregnancy outcomes and complications associated with parasitic infections were estimated using multiple logistic regression models. A p-value of less than 5 % was considered statistically significant. RESULTS: The most prevalent parasitic infection recorded was malaria (17.0 %), while helminths and amebiasis were infrequently recorded (0.6 % vs. 0.7 %, respectively). Women who had malaria during pregnancy had 13 % increased odds of having a preterm delivery (OR = 1.13; 95 % CI: 1.01-1. 26) as compared to those who were not infected. They also had 33 % increased odds of getting maternal anemia (OR = 1.33; 95 % CI: 1.11-1.72). Likewise, pregnant women who were recorded with helminths infections had 29 % increased odds of having maternal anemia as compared to those who had no helminths infection (OR = 1.29; 95 % CI:0.48-3.53). Moreover, pregnant women who were recorded to have amebiasis had 79 % increased odds of having a preterm delivery as compared to those who had no ameba infection (OR = 1.79; 95 % CI: 1.12-2.91). CONCLUSIONS: Malaria was the prevalent parasitic infection in the studied population while helminth and ameba infections were infrequently reported. These parasitic infections were also associated with increased risk of anemia and delivery of a preterm infant. These were the only three infections/infestations which were evaluated. Our analysis revealed that malaria, helminth and ameba infections during pregnancy is dangerous and has life threatening consequences. This highlight the need to provide early diagnosis and treatment for infected women to prevent pregnancy complications and associated adverse pregnancy outcomes. PMID- 26874789 TI - Photopolymerization study and adhesive properties of self-etch adhesives containing bis(acyl)phosphine oxide initiator. AB - OBJECTIVE: This paper investigates the photo-co-polymerization behavior of a blend of a diacrylamide (DEBAAP) with a phosphonylated acidic monomer using either bis(acyl)phosphine oxide or camphorquinone/amine as photo-initiator and studies the effect of variation of the structure of the phosphonylated acidic monomer on the shear bond strength to human dentin. METHODS: Photopolymerization kinetics has been assessed through the use of photo-DSC with either initiating system and with and without a phosphonic acid monomer, while the shear bond strengths (SBS) of dentin bonding agents formulated with several phosphonylated acidic monomers have been evaluated by macro SBS testing on human dentin. RESULTS: Photo-DSC results show that bis(acyl)phosphine oxide initiates a faster polymerization than camphorquinone/amine and that both photopolymerizations are accelerated by the phosphonic acid monomer. Similar results were obtained between adhesives based on camphorquinone/amine and a commercial adhesive (AdheSE, Ivoclar-Vivadent, Schaan, Liechtenstein). The best performances were obtained when BAPO was used as the initiator, in many cases far better than the commercial adhesive. Adhesive SEA6 based on difluoromethylphosphonic acid C demonstrated the best adhesion results of this study. Significance The bis(acyl)phosphine oxide photo-initiator causes faster photopolymerization of two-step self-etching dental adhesive, and its use could yield better bonding performance. PMID- 26874790 TI - Headache and hand numbness in a young female. PMID- 26874791 TI - Left Ventricular Non-compaction in Holt-Oram Syndrome. AB - Holt-Oram Syndrome is an autosomal dominant condition with complete penetrance and which involves upper limb skeletal and cardiac abnormalities. The latter can be structural defects or involve the conduction system. This report details the occurrence of left ventricular non-compaction in multiple family members with Holt-Oram Syndrome. It is recommended that patients with the Holt-Oram Syndrome be considered for comprehensive cardiac evaluation to exclude non-compaction cardiomyopathy as this may have significant prognostic implications. PMID- 26874792 TI - The Relationships of the Maxillary Sinus With the Superior Alveolar Nerves and Vessels as Demonstrated by Cone-Beam CT Combined With MU-CT and Histological Analyses. AB - There are no available detailed data on the three-dimensional courses of the human superior alveolar nerves and vessels. This study aimed to clarify the relationships of the maxillary sinus with the superior alveolar nerves and vessels using cone-beam computed tomography (CT) combined with MU-CT and histological analyses. Digital imaging and communication in medicine data obtained from the scanned heads/maxillae of cadavers used for undergraduate/postgraduate dissection practice and skulls using cone-beam CT were reconstructed into three-dimensional (3D) images using software. The 3D images were compared with MU-CT images and histological sections. Cone-beam CT clarified the relationships of the maxillary sinus with the superior alveolar canals/grooves. The main anterior superior alveolar canal/groove ran anteriorly through the upper part of the sinus and terminated at the bottom of the nasal cavity near the piriform aperture. The main middle alveolar canal ran downward from the upper part of the sinus to ultimately join the anterior one. The main posterior alveolar canal ran through the lateral lower part of the sinus and communicated with the anterior one. Histological analyses demonstrated the existence of nerves and vessels in these canals/grooves, and the quantities of these structures varied across each canal/groove. Furthermore, the superior dental nerve plexus exhibited a network that was located horizontally to the occlusal plane, although these nerve plexuses appeared to be the vertical network that is described in most textbooks. In conclusion, cone-beam CT is suggested to be a useful method for clarifying the superior alveolar canals/grooves including the nerves and vessels. PMID- 26874793 TI - A Concept for the analysis of repeatability and precision of corneal shape measurements. AB - We propose a framework for the analysis of the repeatability and precision of corneal elevation and the repeatability of corneal thickness data measured by clinically used topographers and tomographers. The repeatability is given by the standard deviation of different measurements of the same eye for each data point. The differences between measurements can partially be explained by different positions of the eye at each measurement. The precision is given by the standard deviation of the data after correction for displacements (decentration, tilts, rotations). The applicability is demonstrated using measurements of the Pentacam HR [1] (Oculus Optikgerate GmbH, Wetzlar, Germany) Scheimpflug tomographer. It provides anterior corneal elevation data with a precision that was almost limited by the axial resolution of 1MUm in the central 6mm zone. This is approximately five times better than the precision of the posterior elevation. The results can be applied to surface approximation of the exported corneal elevation data and give a measure for the goodness of the fit. PMID- 26874795 TI - The relationships between serum cytokine levels and tumor infiltrating immune cells and their clinical significance in colorectal cancer. AB - Increased inflammatory cell infiltration correlates to improved survival in colorectal cancer (CRC). Development and progression of CRC is associated with alterations in serum cytokine levels but their significance is not well defined. In this study, we investigated the relationships between the serum levels of 13 cytokines and the densities of eight types of tumor infiltrating inflammatory cells and their impact on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) in a prospectively recruited group of 147 CRC patients. There were strong positive correlations between the serum concentrations of different cytokines, as well as between the different types of tumor infiltrating immune cells, whereas the associations between serum cytokines and tumor infiltrating immune cells were generally weak. High serum IL-12 levels associated with increased densities of peritumoral CD8(+) T cells, intraepithelial CD3(+) T cells and intratumoral neutrophils, while high serum CCL4 levels associated with increased densities of peritumoral CD68(+) cells. In multivariate survival models, increased infiltration of intraepithelial CD3(+) T cells and increased serum CCL4 associated with improved DFS, whereas higher intratumoral CD83(+) dendritic cell density and increased serum interferon gamma levels associated with improved CSS and OS. Also high density of peritumoral CD3(+) T cells associated with improved CSS. In conclusion, serum cytokines and tumor infiltrating immune cells in CRC represent entities with high intragroup correlations but relatively weak intergroup correlations. The results suggest that tumor infiltrating CD3(+) T cells, CD83(+) dendritic cells, serum CCL4 and serum interferon gamma represent relevant markers of disease outcome. PMID- 26874796 TI - Spur cell anemia in the setting of progressive liver allograft failure. PMID- 26874794 TI - Calpain-1 and Calpain-2: The Yin and Yang of Synaptic Plasticity and Neurodegeneration. AB - Many signaling pathways participate in both synaptic plasticity and neuronal degeneration. While calpains participate in these phenomena, very few studies have evaluated the respective roles of the two major calpain isoforms in the brain, calpain-1 and calpain-2. We review recent studies indicating that calpain 1 and calpain-2 exhibit opposite functions in both synaptic plasticity and neurodegeneration. Calpain-1 activation is required for the induction of long term potentiation (LTP) and is generally neuroprotective, while calpain-2 activation limits the extent of potentiation and is neurodegenerative. This duality of functions is related to their associations with different PDZ-binding proteins, resulting in differential subcellular localization, and offers new therapeutic opportunities for a number of indications in which these proteases have previously been implicated. PMID- 26874797 TI - Response of human macrophages to wound matrices in vitro. AB - Chronic wounds remain a major burden to the global healthcare system. Myriad wound matrices are commercially available but their mechanisms of action are poorly understood. Recent studies have shown that macrophages are highly influenced by their microenvironment, but it is not known how different biomaterials affect this interaction. Here, it was hypothesized that human macrophages respond differently to changes in biomaterial properties in vitro with respect to phenotype, including pro-inflammatory M1, anti-inflammatory M2a, known for facilitating extracellular matrix deposition and proliferation, and M2c, which has recently been associated with tissue remodeling. Using multiple donors, it was found that collagen scaffolds cross-linked with 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) promoted the least inflammatory phenotype in primary human macrophages compared with scaffolds cross-linked with formaldehyde or glutaraldehyde. Importantly, gene expression analysis trends were largely conserved between donors, especially TNFa (M1), CCL22 (M2a), and MRC1 (M2a). Then the response of primary and THP1 monocyte derived macrophages to four commercially available wound matrices were compared Integra Dermal Regeneration Template (Integra), PriMatrix Dermal Repair Scaffold (PriMatrix), AlloMend Acellular Dermal Matrix (AlloMend), and Oasis Wound Matrix (Oasis). Gene expression trends were different between primary and THP1 monocyte derived macrophages for all six genes analyzed in this study. Finally, the behavior of primary macrophages cultured onto the wound matrices over time was analyzed. Integra and Oasis caused down-regulation of M2a markers CCL22 and TIMP3. PriMatrix caused up-regulation of TNFa (M1) and CD163 (M2c) and down regulation of CCL22 and TIMP3 (both M2a). AlloMend caused up-regulation in CD163 (M2c). Lastly, Oasis promoted the largest increase in the combinatorial M1/M2 score, defined as the sum of M1 genes divided by the sum of M2 genes. This preliminary study suggested that biomaterials influenced the wound microenvironment to affect macrophage phenotype. PMID- 26874798 TI - Height and Depth Guidelines for Anatomic Femoral Tunnels in Anterior Cruciate Ligament Reconstruction: A Cadaveric Study. AB - PURPOSE: To develop guidelines for femoral tunnel placement based on height and depth on the lateral wall of the notch and to apply these guidelines arthroscopically to show tunnel placements within the anterior cruciate ligament (ACL) femoral insertion site. METHODS: Twelve cadaveric knees were dissected to define the centers of the femoral ACL attachment and its anteromedial (AM) and posterolateral (PL) bundles. In 90 degrees of flexion, the height and depth of each center were determined relative to the low point on the lateral intercondylar notch. Radiographic grid measurements were made to validate these measurements. Subsequently, the measurement guidelines were applied arthroscopically in 10 new cadaveric knees to evaluate their accuracy for an anatomic single-bundle femoral tunnel. Interobserver reliability analysis was evaluated with the intraclass correlation coefficient. RESULTS: In 90 degrees of flexion, the height of the ACL center was 8.7 +/- 0.6 mm from the low point of the lateral notch; PL center, 7.2 +/- 1.2 mm; and AM center, 9.6 +/- 1.1 mm. Relative to the low point, the ACL center was 1.7 +/- 1.7 mm posterior, the PL center was 3.4 +/- 1.5 mm anterior, and the AM center was 4.9 +/- 1.7 mm posterior (intraclass correlation coefficient, 0.859). Radiographic grid measurements were consistent with the direct measurements. Application of the guidelines arthroscopically with or without the assistance of a 7-mm offset aimer placed all guide pins for tunnels within the femoral ACL footprint, with 90% within 4 mm of the ACL center. CONCLUSIONS: This study showed in cadaveric knees in 90 degrees of flexion that the center of the ACL can be located on the lateral notch at a height of 8.7 +/- 0.6 mm from the lowest point and anterior 11.5 +/- 1.3 mm from the deepest point. How anatomic tunnels can be placed using these measurements was also shown in cadaveric knees. CLINICAL RELEVANCE: An anatomic femoral tunnel for ACL reconstruction can be placed using height and depth guidelines. PMID- 26874799 TI - Effect of Human Serum and 2 Different Types of Platelet Concentrates on Human Meniscus Cell Migration, Proliferation, and Matrix Formation. AB - PURPOSE: To evaluate the effect of 10% human serum (HS), 5% platelet-rich plasma (PRP), and 5% autologous conditioned plasma (ACP) on migration, proliferation, and extracellular matrix (ECM) synthesis of human meniscus cells. METHODS: Cell migration and proliferation on stimulation with HS, PRP, and ACP were assessed by chemotaxis assays and measurement of genomic DNA content. Meniscus cells were cultivated in pellets stimulated with 10% HS, 5% PRP, or 5% ACP. Meniscal ECM formation was evaluated by histochemical staining of collagen type I, type II, and proteoglycans and by analysis of fibrochondrocyte marker gene expression. RESULTS: Human meniscus cells were significantly attracted by all 3 blood-derived products (10% HS and 5% ACP: P = .0001, 5% PRP: P = .0002). Cell proliferation at day 9 was significantly increased on stimulation with 10% HS (P = .0001) and 5% PRP (P = .0002) compared with 5% ACP and controls. Meniscus cell pellet cultures showed the formation of a well-structured meniscal ECM with deposition of collagen type I, type II, and proteoglycans on stimulation with 10% HS, whereas 5% PRP or 5% ACP resulted in the formation of an inhomogeneous and more fibrous ECM. Stimulation with 10% HS and 5% ACP showed a significant induction of fibrochondrocyte marker genes such as aggrecan (HS: P = .0002, ACP: P = .0147), cartilage oligomeric matrix protein (HS: P = .0002, ACP: P = .0005), and biglycan (HS: P = .0002, ACP: P = .0003), whereas PRP showed no inducing effect. CONCLUSIONS: Among all tested blood-derived products, only stimulation with HS showed the formation of a meniscal ECM as well as positive cell proliferating and migrating effects in vitro. Regarding a potential biological repair of nonvascular meniscus lesions, our results may point toward the use of HS as a beneficial augment in regenerative meniscus repair approaches. CLINICAL RELEVANCE: Our findings may suggest that HS might be a beneficial augment for meniscus repair. PMID- 26874800 TI - Does Gracilis Preservation Matter in Anterior Cruciate Ligament Reconstruction? A Systematic Review. AB - PURPOSE: To analyze the effect of gracilis harvest on hamstring strength, patient reported outcomes, and anterior knee laxity after anterior cruciate ligament (ACL) reconstruction. METHODS: A systematic review of the literature was performed to identify studies comparing the results of semitendinosus (ST) versus semitendinosus-gracilis (ST-G) harvest for ACL reconstruction. A meta-analysis using a random effects model was performed to determine overall pooled estimates of effect for the influence of additional gracilis harvest on hamstring strength, patient-reported outcomes, and anterior knee laxity after ACL reconstruction. RESULTS: Twelve studies were identified and included in the review. ST-G harvest was noted to decrease hamstring isokinetic strength at 60 degrees per second by 3.85% relative to isolated ST harvest (P = .01). Decreased isometric strength was also noted in the ST-G harvest group at both 90 degrees of flexion (mean difference: 5.55%; P = .03) and 105 degrees to 110 degrees of flexion (mean difference: 13.68%; P = .003). Active knee flexion angle loss was also noted to be greater in the ST-G harvest group (mean difference: 3.91 degrees ; P = .006). No differences were found in isokinetic strength at 180 degrees to 240 degrees per second (mean difference: 3.20%; P = .08), patient-reported outcome scores (mean difference: 1.87 points; P = .06), or anterior knee laxity (mean difference: 0.03 mm; P = .78) based on gracilis harvest. CONCLUSIONS: The addition of gracilis harvest to an isolated ST harvest for ACL reconstruction results in statistically significant, but likely not clinically relevant differences in isokinetic and isometric hamstring strength as well as patient reported outcomes. Hamstring strength deficits may be larger at higher flexion angles. LEVEL OF EVIDENCE: Level III, systematic review of level I-III studies. PMID- 26874801 TI - Morphology of the Lesser Tuberosity and Intertubercular Groove in Patients With Arthroscopically Confirmed Subscapularis and Biceps Tendon Pathology. AB - PURPOSE: To evaluate for an association between the morphology of the lesser tuberosity and intertubercular groove and subscapularis tendon tears and biceps tendon pathology. METHODS: Sixty-six patients with arthroscopically confirmed subscapularis tendon tears were compared with 59 demographically matched control patients who underwent magnetic resonance imaging or computed tomography arthrography examination of the shoulder. Measurements of the lesser tuberosity and intertubercular groove included maximum depth of the intertubercular groove, intertubercular groove depth at the midpoint of the glenoid, lesser tuberosity length, length from the top of the humeral head to the point of maximum depth of the intertubercular groove, length from the top of the humeral head to the top of the lesser tuberosity, and medial wall angle and depth. RESULTS: Patients with subscapularis tears showed a significantly decreased depth of the intertubercular groove at the mid glenoid (P = .01), shorter length of the lesser tuberosity (P = .002), and greater distance from the top of the humeral head to the top of the lesser tuberosity (P = .02). There was a trend toward a decreased medial wall angle (P = .07) and greater distance from the top of the humeral head to the point of maximum intertubercular groove depth (P = .06). Patients with biceps tendon pathology showed a significantly decreased depth of the intertubercular groove at the mid glenoid (P = .001), shorter length of the lesser tuberosity (P = .0003), greater distance from the top of the humeral head to the top of the lesser tuberosity (P = .01), and decreased medial wall angle (P = .01) and depth (P = .03). CONCLUSIONS: There are several morphologic factors related to the lesser tuberosity and intertubercular groove that are associated with both subscapularis tendon tears and biceps tendon pathology. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 26874802 TI - Killing two birds or more with one stone. PMID- 26874803 TI - Grammar of binding in the languages of the world: Unity versus diversity. AB - Cole, Hermon, and Yanti (2015) present a number of far-reaching conclusions about language universals on the basis of their study of the anaphoric systems of the Austronesian languages of Indonesia. The present contribution critically assesses these conclusions. It reports a further set of data, and shows that contra to what these authors argue, the systems they discuss can be straightforwardly accounted for by a simple set of universal principles plus properties of the vocabulary of the languages involved. I conclude this article with some remarks on acquisition. PMID- 26874804 TI - Bile acids in drug induced liver injury: Key players and surrogate markers. AB - Bile acid research has gained great momentum since the role of bile acids as key signaling molecules in the enterohepatic circulation was discovered. Their physiological function in regulating their own homeostasis, as well as energy and lipid metabolism make them interesting targets for the pharmaceutical industry in the context of diseases such as bile acid induced diarrhea, bile acid induced cholestasis or nonalcoholic steatohepatitis. Changes in bile acid homeostasis are also linked to various types of drug-induced liver injury (DILI). However, the key question whether bile acids are surrogate markers for monitoring DILI or key pathogenic players in the onset and progression of DILI is under intense investigation. The purpose of this review is to summarize the different facets of bile acids in the context of normal physiology, hereditary defects of bile acid transport and DILI. PMID- 26874805 TI - Reply to Stephen B. Williams and Ashish M. Kamat's Letter to the Editor re: Samantha Cambier, Richard J. Sylvester, Laurence Collette, et al. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol 2016;69:60-9. PMID- 26874807 TI - Do the Benefits of Phosphodiesterase Type 5 Inhibitors in Male Lower Urinary Tract Symptoms Go Beyond Improved Symptoms? PMID- 26874806 TI - Robot-assisted Versus Open Radical Prostatectomy: A Contemporary Analysis of an All-payer Discharge Database. AB - BACKGROUND: More than a decade since its inception, the benefits and cost efficiency of robot-assisted radical prostatectomy (RARP) continue to elicit controversy. OBJECTIVE: To compare outcomes and costs between RARP and open RP (ORP). DESIGN, SETTING, AND PARTICIPANTS: A cohort study of 629 593 men who underwent RP for localized prostate cancer at 449 hospitals in the USA from 2003 to 2013, using the Premier Hospital Database. INTERVENTION: RARP was ascertained through a review of the hospital charge description master for robotic supplies. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Outcomes were 90-d postoperative complications (Clavien), blood product transfusions, operating room time (ORT), length of stay (LOS), and direct hospital costs. Propensity-weighted regression analyses accounting for clustering by hospitals and survey weighting ensured nationally representative estimates. RESULTS AND LIMITATIONS: RARP utilization rapidly increased from 1.8% in 2003 to 85% in 2013 (p<0.001). RARP patients (n=311 135) were less likely to experience any complications (odds ratio [OR] 0.68, p<0.001) or prolonged LOS (OR 0.28, p<0.001), or to receive blood products (OR 0.33, p=0.002) compared to ORP patients (n=318 458). The adjusted mean ORT was 131min longer for RARP (p=0.002). The 90-d direct hospital costs were higher for RARP (+$4528, p<0.001), primarily attributed to operating room and supplies costs. Costs were no longer signficantly different between ORP and RARP among the highest-volume surgeons (>=104 cases/yr; +$1990, p=0.40) and highest-volume hospitals (>=318 cases/yr; +$1225, p=0.39). Limitations include the lack of oncologic characteristics and the retrospective nature of the study. CONCLUSIONS: Our contemporary analysis reveals that RARP confers a perioperative morbidity advantage at higher cost. In the absence of large randomized trials because of the widespread adoption of RARP, this retrospective study represents the best available evidence for the morbidity and cost profile of RARP versus ORP. PATIENT SUMMARY: In this large study of men with prostate cancer who underwent either open or robotic radical prostatectomy, we found that robotic surgery has a better morbidity profile but costs more. PMID- 26874808 TI - Re: Samantha Cambier, Richard J. Sylvester, Laurence Collette, et al. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette Guerin. Eur Urol 2016;69:60-9. PMID- 26874809 TI - Effects of Testosterone Replacement Therapy on Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis. AB - CONTEXT: There is a potential risk that testosterone replacement therapy (TRT) may exacerbate lower urinary tract symptoms (LUTS) among aging men with late onset hypogonadism (LOH) because of testosterone's growth-promoting effects on the prostate. OBJECTIVE: To compare the change in LUTS severity as assessed using the International Prostate Symptom Score (IPSS) between men receiving TRT versus placebo for the treatment of LOH. EVIDENCE ACQUISITION: Systematic search of MEDLINE, Embase, ClinicalTrials.gov, and The Cochrane Library for randomized controlled trials of TRT for LOH published between January 1992 and September 2015. Studies were eligible for inclusion if they were a randomized control trial, used TRT, and assessed LUTS outcomes using the IPSS. Estimates were pooled using random effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. EVIDENCE SYNTHESIS: Data were extracted from 14 trials involving 2029 participants. The average age was 64.5 yr and the average follow-up was 34.4 mo. Seven studies used topical, five used injectable, and two used oral testosterone. There was no statistically significant difference in pooled changes in IPSS from baseline to follow up in men treated with TRT compared with those receiving placebo (-0.41 points [95% confidence interval: 0.89 to 0.07; I(2)=0%, p=0.28] vs. 0.12 points [95% confidence interval: -0.32 to 0.55; I(2)=0%, p=0.81], between-group difference p>0.05). No between-group differences were noted in subanalyses that controlled for potential confounders such as type of testosterone, change in testosterone, aging male symptom scale, or prostate-specific antigen levels (p>0.05 for all comparisons). CONCLUSIONS: In this meta-analysis of 14 clinical trials of TRT for LOH, the change in IPSS was similar among men receiving TRT versus placebo, suggesting that TRT treatment does not worsen LUTS among men with LOH. PATIENT SUMMARY: In this analysis of 14 clinical trials, testosterone replacement therapy did not worsen lower urinary tract symptoms among men being treated for late-onset hypogonadism. PMID- 26874811 TI - Lifelong Learning in Practice: The Age of Discussion Through Social Media. PMID- 26874812 TI - [Amyloidosis: Up-to-date]. AB - Amyloidosis is mainly a systemic disease belonging to protein-folding diseases. The past 10 years have shown significant progress in typing and the clinical management of amyloidosis, in the identification of novel prognostic markers for risk-stratification, and also in the development of new therapeutic agents. Biological molecular techniques are now able to type amyloidosis which were unidentified. Cardiac MRI and biomarkers allow a precise risk-stratification, especially in AL amyloidosis. If necessary, this prognostic evaluation may lead to rapid changes in the chemotherapy treatment. Emerging treatments rely on biotherapies, gene therapy, immunotherapy and blocking analogous agents. They give hope about an increase of survival of patients with systemic amyloidosis. PMID- 26874810 TI - Long-term Impact of Mode of Delivery on Stress Urinary Incontinence and Urgency Urinary Incontinence: A Systematic Review and Meta-analysis. AB - CONTEXT: Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain. OBJECTIVE: To investigate the long-term impact of delivery mode on SUI and UUI. EVIDENCE ACQUISITION: We searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI >=1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias. EVIDENCE SYNTHESIS: Pooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56-2.19; I(2)=57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p=0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84-1.45; I(2)=50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02-1.65; I(2)=37%; risk difference: 2.6%). CONCLUSIONS: Compared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%. PATIENT SUMMARY: In this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency. PMID- 26874813 TI - [Incidental finding of situs inversus totalis using scintigraphy to rule out gastrointestinal bleeding and Meckel's diverticulum]. PMID- 26874814 TI - Ganglioglioma arising from olfactory sheath: A rare site of an uncommon tumor. AB - Gangliogliomas are rare slow growing tumors with a mixed population of dysplastic ganglion cells and glial components, reported at variable sites within the central nervous system, including the frontal, parietal and occipital lobes, the striatum, cerebellum, pituitary and pineal glands as well as the spinal cord. Rarely gangliogliomas have been reported arising within the cranial nerves, including the optic and trigeminal nerve. We present the first patient, to our knowledge, where such a tumor originated from the olfactory sheath. Migration defects leading to entrapment of sensory neurons during development is believed to be responsible for the pathogenesis of these lesions. The extent of surgical extirpation and histopathological anaplasia are important prognosticators. While gangliogliomas are rare tumors, it is crucial to consider them in the differential diagnosis of non-enhancing, poorly localized lesions along the cranial nerves. PMID- 26874815 TI - Subtle Cognitive Dysfunction in Resolving High Altitude Cerebral Edema Revealed by a Clock Drawing Test. AB - High altitude cerebral edema (HACE) is a life-threatening condition that can affect people who ascend to altitudes above 2500 m. Altered mental status and the presence of ataxia distinguishes HACE from acute mountain sickness (AMS). We describe a patient with subtle cognitive dysfunction, likely due to HACE that had not fully resolved. When he initially presented, the patient appeared to have normal mental status and was not ataxic. The diagnosis of HACE was missed initially but was made when further history became available. Cognitive dysfunction was then diagnosed based on abnormal performance of a clock drawing test. A formal mental status examination, using a clock drawing test, may be helpful in assessing whether a patient at high altitude with apparently normal mental status and with normal gait has HACE. PMID- 26874816 TI - An exploration of familial associations of two movement pattern-derived subgroups of chronic disabling low back pain; a cross-sectional cohort study. AB - BACKGROUND: Altered movement patterns with pain have been demonstrated in children, adolescents and adults with chronic disabling low back pain (CDLBP). A previously developed classification system has identified different subgroups including active extension and multidirectional patterns in patients with CDLBP. While familial associations have been identified for certain spinal postures in standing, it is unknown whether a familial relationship might exist between movement pattern-derived subgroups in families with CDLBP. OBJECTIVES: This study explored whether familial associations in movement pattern-derived subgroups within and between members of families with CDLBP existed. DESIGN: Cross sectional cohort study. METHOD: 33 parents and 28 children with CDLBP were classified into two subgroups based on clinical analysis of video footage of postures and functional movements, combined with aggravating factors obtained from Oswestry Disability Questionnaire. Prevalence of subgroups within family members was determined, associations between parent and child's subgroup membership was evaluated using Fisher's exact test, and spearman's correlation coefficient was used to determine the strength of association between familial dyads. RESULTS: The majority of parents were classified as active extenders, sons predominately multidirectional and daughters were evenly distributed between the two subgroups. No significant association was found when comparing subgroups in nine parent-child relationships. CONCLUSIONS: The exploration of a small cohort of family dyads in this study demonstrated that children's movement pattern derived subgroups could not be explained by their parents' subgroup membership. These results cannot be generalised to the CLBP population due to this study's small sample. Larger sample studies are needed to further elucidate this issue. PMID- 26874817 TI - Feasibility of the subgroup criteria included in the treatment-strategy-based (TREST) classification system (CS) for patients with non-specific low back pain (NSLBP). AB - BACKGROUND: The new treatment-strategy based (TREST) classification system (CS) is in its exploratory phase with potential to impact clinical decision-making in the management of non-specific low back pain (NSLBP). OBJECTIVE: To evaluate the feasibility of subgroup criteria included in TREST subgroups: pain modulation, stabilization exercise, mobilization, and training. METHODS: An observational cross-sectional investigation involving a secondary analysis of data from 128 examinations of NSLBP patients, categorized individually by four examiners into one of the TREST subgroups. Four separate multivariate logistic regression analyses in two models were applied to identify how examiners applied judgments on pain intensity, disability and predetermined signs and symptoms to categorize patients into subgroups. RESULTS: Associations were found between the presence of "neurological signs and symptoms" (OR 5.5, 95% CI 1.9-16), "irritability" (OR 3.0, 95% CI 3.2-20) and disability (ODI) >30 (OR 8.5, 95% CI 3-20) and the subgroup pain modulation; between the presence of "bilateral spinal signs" (OR 5.6, 95% CI 1.1-29) and the subgroup stabilization exercise; between the presence of "specific segmental signs" (OR 4.0, 95% CI 1.2-14) and ODI <=30 (OR 0.2, 95% CI 0.1-0.6) and the subgroup mobilization; between the presence of "neurological signs and symptoms" (OR 0.2, 95% CI 0.1-0.4) and the subgroup training. CONCLUSIONS: Findings preliminary support feasibility of TREST subgroup criteria: neurological deficits, irritability, bilateral spinal signs, segmental signs and disability in the categorization of NSLBP patients. Further validation of the TREST classification system is required to establish its value in clinical reasoning and impact on patient outcomes. PMID- 26874820 TI - Fractional carbon-dioxide (CO2) laser-assisted topical therapy for the treatment of onychomycosis. AB - BACKGROUND: Inability of topical medications to penetrate via nail plate brings a great challenge to clinicians in treating onychomycosis. Furthermore, oral medications are not appropriate for all patients because of drug interactions, adverse effects, and contraindications. OBJECTIVE: We sought to evaluate the clinical efficacy of fractional carbon-dioxide laser-assisted topical therapy for onychomycosis. METHODS: In total, 75 patients with 356 onychomycotic nails confirmed by mycologic examination were included in this study. All the affected nails received 3 sessions of laser therapy at 4-week intervals and once-daily application of terbinafine cream for 3 months. RESULTS: In all, 94.66% and 92% of the treated patients were potassium hydroxide and culture negative, respectively, after 3 months of treatment. However, only 84% and 80% were potassium hydroxide and culture negative, respectively, at 6 months of follow-up. Using Scoring Clinical Index for Onychomycosis electronic calculator, 73.33% of the patients scored higher than 6 and 26.66% of the patients scored 6 or less. Those who scored more than 6 were evaluated clinically and 98.18% of them showed response to treatment at 3 months and 78.18% of them at 6 months of follow-up. LIMITATION: Lack of control group and short duration of follow-up are limitations. CONCLUSIONS: Fractional carbon-dioxide laser therapy combined with topical antifungal was found to be effective in the treatment of onychomycosis. However, randomized clinical studies are needed before it can be widely used in clinics. PMID- 26874819 TI - Cutaneous T-cell lymphoma (CTCL): Current practices in blood assessment and the utility of T-cell receptor (TCR)-Vbeta chain restriction. AB - BACKGROUND: Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. OBJECTIVE: We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vbeta analysis by flow cytometry. METHODS: We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. RESULTS: There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vbeta testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. LIMITATIONS: Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. CONCLUSION: We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vbeta testing should be considered in future diagnostic and staging algorithms. PMID- 26874821 TI - Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation. AB - BACKGROUND: Disease-specific skin lesions are rare in patients with multiple myeloma (MM). OBJECTIVE: We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. METHODS: We identified 13 patients with cutaneous lesions of MM. RESULTS: Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. LIMITATIONS: The study group was relatively small. CONCLUSIONS: Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. PMID- 26874823 TI - IMF-lending programs and suicide mortality. AB - While the economic consequences of IMF programs have been extensively analyzed in the literature, much less is known about how key welfare indicators, including suicide-mortality rates, correlate with countries' participation in such programs. This paper examines the impact of IMF lending on suicide mortality, using data from 30 developing and transition countries that received non concessionary IMF loans during 1991-2008. Our results support the hypothesis of a positive causal relationship between suicide mortality and participation in IMF programs but reveal no systematic suicide-increasing effect from the size of IMF loans. This holds after accounting for self-selection into programs, resulting from the endogeneity of a country's decision to resort to the IMF for funding, and after controlling for standard socio-economic influences on suicidal behaviour. In particular, we find a positive aggregate suicide-mortality differential due to IMF-program participation of between 4 and 14 percentage points. We also find that the positive association between suicides and program participation is stronger and more robust among males. Comparing age groups, individuals belonging to the age group 45-to-64 exhibit the highest increase in suicide due to program-participation, which amounts to over 18 percentage points. Overall, our results imply that when countries are exposed to IMF programs in an attempt to resolve their economic problems, social-safety nets need to be designed to protect the adversely-affected part of the population. PMID- 26874822 TI - Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection. AB - Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-gamma and interleukin (IL)-4 ex-vivo enzyme linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl ceramide (alphaGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0.03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8alpha and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0.0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0.006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. PMID- 26874824 TI - The myth of the total institution: Written narratives of patients' views of sanatorium care 1908-1959. AB - Drawing on written narratives by 72 former sanatorium patients, this article explores, from patients' perspectives, the nature of the relationships between patients and staff in a Swedish sanatorium during the first half of the twentieth century. These narratives are discussed in the context of the total institution. This article suggests that this phenomenon was marked by inconsistencies that can be understood in terms of its situational and contradictory characteristics. Simultaneously, these narratives are in opposition to the assumption of the static and powerless patient adapted only to suit the logic of the institution. PMID- 26874825 TI - Poverty dynamics in Germany: Evidence on the relationship between persistent poverty and health behavior. AB - Previous studies have found poverty to be related to lower levels of health due to poor health behavior such as unhealthy eating, smoking or less physical activity. Longer periods of poverty seem to be especially harmful for individual health behavior. Studies have shown that poverty has a dynamic character. Moreover, poverty is increasingly regarded as being a multidimensional construct and one that considers more aspects than income alone. Against this background this paper analyzes the relationship between health behavior and persistent spells of income poverty as well as a combined poverty indicator using data of the German Socio-Economic Panel (2000-2010). Next to cross-sectional logistic regression models we estimate fixed-effects models to analyze the effect of persistent poverty on dietary behavior, tobacco consumption, and physical activity. Cross-sectional results suggest that persistent poverty is related to poor health behavior, particularly regarding tobacco consumption and physical activity. Results also show that multidimensional and dynamic aspects of poverty matter. Complementary panel analyses reveal negative effects for the combined poverty indicator only for dietary behavior in the total sample. However, by analyzing the sample by gender we identify further effects of persistent poverty on health behavior. The analyses show that not only do individuals in poverty but also those in precarious situations show health-damaging behavior more often. PMID- 26874826 TI - [Conservative management of upper tract urinary fistulae using ureteral trans vesico-parietal stent]. AB - OBJECTIVES: Ureteral stents and ureteral catheters externalized through the urethra are not ideal solutions to manage complicated upper urinary tract fistulae. We sought an effective method of drainage, minimally invasive, reproducible allowing a rapid patient's discharge. PATIENTS AND METHODS: Between November 2013 and February 2015, an ureteral stent was exteriorized in trans vesico-parietal by an endoscopic and percutaneous access in patients with complicated upper urinary tract fistulae. Monitoring of tolerance, complications and urinary fistula healing was performed. RESULTS: Nine consecutive patients had an ureteral stent exteriorized in trans-vesico-parietal to manage complicated upper urinary tract fistulae. There was no failure in introducing the catheter, or postoperative complication. Catheters were left in place on average 36.1days (24-55). The patients were able to return home with the catheter in place in 77.8% of cases. The tolerance of the catheter was good. All fistulae were able to be treated conservatively at the end of the drainage period. CONCLUSION: Trans vesico-parietal ureteral catheters enable efficient and reproducible conservative treatment of upper tract urinary fistulae regardless of their cause. LEVEL OF EVIDENCE: 5. PMID- 26874827 TI - Fertility defects in Surfactant associated protein D knockout female mice: altered ovarian hormone profile. AB - Surfactant associated protein D (SFTPD, also known as SP-D), a pattern recognition molecule, is an integral component of the mucosal immune system of female reproductive tract (FRT). In addition to host defense functions in the FRT, recent evidences indicate immunomodulatory role of SFTPD in parturition and pre-term labor. Regulation of SFTPD expression by ovarian hormones in the mouse uterus implicates SFTPD of FRT in pregnancy establishment and maintenance. In the current study, we attempted to decipher the functional relevance of SFTPD in FRT by characterizing the fertility parameters of surfactant associated protein D knockout (Sftpd(tm1Jhf)/Sftpd(tm1Jhf)) female mice. Knockout female mice exhibited extended estrous cycle with altered serum profile of ovarian hormones. We also demonstrate altered expression of ovarian hormone receptors and hormone responsive genes ITGB1, LIF and HOXA10 in uteri of these mice. Knockout females mated with wild type males had significantly smaller litter size due to increased pre-implantation embryo loss. We also observed an altered immune profile in knockout mice uteri with elevated levels of inflammatory cytokines, increased numbers of pro-inflammatory monocytes/macrophages and lower FOXP3 levels during the pre-implantation period. LPS administration to pregnant knockout mice did not result in any increase in embryo implantation loss and was associated with a blunted uterine pro-inflammatory response, plausibly due to higher levels of serum progesterone. Taken together, our results demonstrate that SFTPD deficiency affects female fertility, highlighting roles for SFTPD in ovarian and uterine physiology. PMID- 26874828 TI - A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFkappaB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. AB - Our previous studies reported that pattern recognition receptors (PRRs), including the cell surface Toll-like receptors (TLRs) and cytoplasmic NOD-like receptors (NLRs), recognize pathogen-associated molecular patterns (PAMPS) to initiate downstream signal cascades to active immunity responses. Thymic stromal lymphopoietin (TSLP) has recently emerged as a key cytokine in the development of type 2 adaptive immune responses. However, the crosstalk between PRRs and TSLP has not been well elucidated in Aspergillus fumigates keratitis. Our studies demonstrated that HCECs not only respond to TSLP, but also initiate immunological regulation through TSLP/TSLPR/STAT5 signaling pathway. In addition, we revealed that zymosan TLR2 agonist enhanced the expression of TSLP and TSLPR and phosphorylation of STAT5. Furthermore, neutralization of TLR2 with monoclonal Ab prevented the production of TSLP and TSLPR and phosphorylation of STAT5 from increasing which induced by A. fumigatus hyphae. Interestingly, we also found that human recombinant TSLP induced the increase of TLR2 downstream signal molecules, and TSLP knockdown could reduce the increase of TLR2 downstream signaling molecules(MyD88 and NF-kappaB-p65) induced by A. fumigatus hyphae. These studies indicated that HCECs represent a novel target of TSLP, TSLP/TSLPR/STAT5 signaling plays an important role in response to A. fumigatus infection in HCECs, and TLR2 downstream signaling molecules up regulate TSLP/TSLPR/STAT5 signaling as well as TSLP downstream signaling molecules up regulate TLR2/MyD88/NFkappaB-p65 signaling in this phenomenon. PMID- 26874829 TI - MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children. AB - BACKGROUND: The underlying molecular mechanisms leading to asthma remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. However, the role of miRNAs, specifically microRNA-21 (miRNA- 21), in the regulation of allergic airway inflammation is not well defined. Our aim was to investigate the serum miRNA- 21 expression levels as potential biomarker in childhood asthma [with, without inhaled corticosteroid (ICS) therapy, and steroid resistant (SR)]; and their possible contributions in disease status, its molecular target interleukin-12 (IL-12) p35, and response to therapy. MATERIALS AND METHODS: This study included 175 children; 95 were asthmatic patients subdivided into 3 groups [40 asthmatic children without ICS, 40 steroid sensitive (SS) asthma children and 15 steroid resistant (SR) asthma children] and 80 were healthy children as healthy controls. The miRNA-21 expressions levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) in all children. Serum IL-12p35 and total IgE levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The expression levels of miRNA-21 were significantly higher in the asthmatic children than in control group (P<0.001); with significantly higher levels in asthmatic patients without ICS or in SR patients compared to SS children (P<0.001). On contrast, serum IL-12p35 levels were significantly decreased in asthmatic patients without ICS therapy or in SR asthma patients as compared to SS patients (P<0.001). Our data revealed that serum miRNA-21 expression levels was significant negatively correlated with serum IL-12p35 levels and FEV1, while it was positively correlated with both sputum and blood eosinophils. Importantly, serum miRNA-21 had a predictive value in differentiating SS from SR patients, with an AUC value of 0.99, specificity of 86.7%, sensitivity of 97.5% and P<0.001. CONCLUSION: This study suggested that serum miRNA-21 is stable and detectable in serum of asthmatic children, which could promise potential biomarker in diagnosis as well as in response to therapy of asthma. PMID- 26874830 TI - Subtalar Arthroereisis Implant Removal in Adults: A Prospective Study of 100 Patients. AB - Subtalar joint arthroereisis (STA) can be used in the management of adult acquired flatfoot deformity (AAFD), including posterior tibial tendon dysfunction. The procedure is quick and normally causes little morbidity; however, the implant used for STA often needs to be removed because of sinus tarsi pain. The present study evaluated the rate and risk factors for removal of the implant used for STA in adults treated for AAFD/posterior tibial tendon dysfunction, including patient age, implant size, and the use of endoscopic gastrocnemius recession. Patients undergoing STA for adult acquired flatfoot were prospectively studied from 1996 to 2012. The inclusion criteria were an arthroereisis procedure for AAFD/posterior tibial tendon dysfunction, age >18 years, and a follow-up period of >=2 years. The exclusion criteria were hindfoot arthritis, age <18 years, and a follow-up period of <2 years. A total of 100 patients (average age 53 years) underwent 104 STA procedures. The mean follow-up period was 6.5 (range 2 to 17) years. The overall incidence of implant removal was 22.1%. Patient age was not a risk factor for implant removal (p = .09). However, implant size was a factor for removal, with 11-mm implants removed significantly more frequently (p = .02). Endoscopic gastrocnemius recession did not exert any influence on the rate of implant removal (p = .19). After STA for AAFD, 22% of the implants were removed. No significant difference was found in the incidence of removal according to patient age or endoscopic gastrocnemius recession. However, a significant difference was found for implant size, with 11 mm implants explanted most frequently. PMID- 26874832 TI - Automatic cytoplasm and nuclei segmentation for color cervical smear image using an efficient gap-search MRF. AB - Accurate and effective cervical smear image segmentation is required for automated cervical cell analysis systems. Thus, we proposed a novel superpixel based Markov random field (MRF) segmentation framework to acquire the nucleus, cytoplasm and image background of cell images. We seek to classify color non overlapping superpixel-patches on one image for image segmentation. This model describes the whole image as an undirected probabilistic graphical model and was developed using an automatic label-map mechanism for determining nuclear, cytoplasmic and background regions. A gap-search algorithm was designed to enhance the model efficiency. Data show that the algorithms of our framework provide better accuracy for both real-world and the public Herlev datasets. Furthermore, the proposed gap-search algorithm of this model is much more faster than pixel-based and superpixel-based algorithms. PMID- 26874831 TI - Treatment of Calcified Insertional Achilles Tendinopathy by the Posterior Midline Approach. AB - The present study investigated the clinical outcomes of the posterior midline approach in the treatment of 34 patients with significantly calcified insertional Achilles tendinopathy. The posterior midline approach was applied for the surgical treatment of 34 patients with chronic significantly calcified insertional Achilles tendinopathy after failed conservative treatment. Gastrocnemius recession was performed simultaneously for patients with gastrocnemius contracture. The Fowler-Philip angle and parallel pitch lines were measured before surgery, and the visual analog scale, Tegner score, and Victorian Institute of Sport tendon study group score were recorded before and after surgery. The mean follow-up period was 45.2 +/- 17.7 (range 24 to 84) months. After surgery, the visual analog scale score had decreased notably, and the Tegner score and Victorian Institute of Sport tendon study group score had increased significantly. The posterior midline approach can achieve satisfactory outcomes in the treatment of significantly calcified insertional Achilles tendinopathy, and gastrocnemius recession (Strayer procedure) should be performed for patients with gastrocnemius contracture to improve the surgical outcome. PMID- 26874833 TI - Country-level correlates of e-cigarette use in the European Union. AB - OBJECTIVES: The aim of this study was to assess the relationship between the prevalence of e-cigarette use and country-level factors across 28 European countries. METHODS: The study objectives were addressed in an ecological design in which both exposures and outcomes were measured at the country level. Data from the Eurobarometer Report, the Eurostat database and the WHO observatory were analyzed. Bivariate and multivariate analyses were performed considering the rates of current and ever smokers of e-cigarettes as dependent variables, and socio-economic factors, health status and policies against tobacco as independent variables. RESULTS: Both the rate of current smokers and ever smokers of e cigarette were positively associated to the offer of help to quit tobacco use (P < 0.01; P = 0.04) and to the raise of taxes on tobacco (P = 0.01; P = 0.01). The warn on dangers of tobacco negatively correlated with the rate of e-cigarette current smokers. The rate of current e-cigarette smokers correlated with the rate of current smokers and with national Gross Domestic Product, while the rate of ever e-cigarette smokers did not correlate with any socio-economic factor. CONCLUSIONS: Our analysis suggests that both policy and non-policy factors are associated with the geographical variability seen in the prevalence of e cigarette use. Policies against the consumption of conventional tobacco products may lead to an increase of e-cigarette smokers. PMID- 26874834 TI - How to review a surgical paper: a guide for junior referees. AB - Reviewing a surgical manuscript is not an easy task, and there is no formal training available for young referees in the early stage of their careers. Accepting a peer review assignment represents a personal honor for the invited referee and a fundamental ethical responsibility towards the scientific community. Designated reviewers must be accomplished and knowledgeable in the area of the respective topic of investigation. More importantly, they must be aware and cognizant about the cardinal ethical responsibility and stewardship for ensuring the preservation of scientific knowledge of unbiased and unquestionable accuracy in the published literature. Accepting a review assignment should never be taken lightly or considered a simple task, regardless of the reviewer's level of seniority and expertise. Indeed, there are multiple challenges, difficulties, and 'hidden dangers' that jeopardize the completion of a high-quality review, particularly in the hands of less experienced or novice reviewers. The present article was designed to provide a brief, concise, and practical guide on how to review manuscripts for the 'junior referee' in the field of surgery. PMID- 26874835 TI - Acute neurological symptoms secondary to hypomagnesemia induced by proton pump inhibitors: a case series. PMID- 26874836 TI - Docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2 positive primary breast cancer. AB - BACKGROUND: The standard primary systemic therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer is anthracyclines and/or taxanes combined with trastuzumab, which demonstrates a high pathological complete response (pCR). A pCR is a predictive marker of prognosis. However, results slightly differ, depending on the hormone receptor status. The efficacy and tolerability of docetaxel, cyclophosphamide, and trastuzumab (HER-TC) as neoadjuvant chemotherapy (NAC) remain unclear. We performed a prospective multicenter study of HER-TC NAC for HER2+ primary breast cancer. METHODS: Eligible patients had a clinical diagnosis of HER2+ invasive breast cancer greater than 1 cm but less than 7 cm and a tumor stage of N0 or N1. T hey were diagnosed between July 2011 and February 2014. For NAC, four cycles of HER-TC (6 mg/kg loading dose, 8 mg/kg, 75, and 600 mg/m2) were administered intravenously every 3 weeks. We investigated the pCR of the primary breast tumors. A pCR was defined as no histological evidence of invasive carcinoma or the appearance of only ductal carcinoma in situ. RESULTS: We enrolled 42 patients. The completion rate for four cycles of HER-TC was 97.6 % (41/42 patients). The overall pCR rate was 43.9 % (18/41 patients). The pCR rate for patients with the luminal HER2 subtype [estrogen receptor (ER)-positive+, HER2+] and the HER2-enriched subtype (ER-, HER2+) was 40.0 % (8/20 patients) and 47.6 % (10/21 patients), respectively. A pCR was achieved with nearly the same probability for each subtype. CONCLUSIONS: Four cycles of HER-TC may be a NAC option for HER2-positive breast cancer. PMID- 26874837 TI - A 'slow pace of life' in Australian old-endemic passerine birds is not accompanied by low basal metabolic rates. AB - Life history theory suggests that species experiencing high extrinsic mortality rates allocate more resources toward reproduction relative to self-maintenance and reach maturity earlier ('fast pace of life') than those having greater life expectancy and reproducing at a lower rate ('slow pace of life'). Among birds, many studies have shown that tropical species have a slower pace of life than temperate-breeding species. The pace of life has been hypothesized to affect metabolism and, as predicted, tropical birds have lower basal metabolic rates (BMR) than temperate-breeding birds. However, many temperate-breeding Australian passerines belong to lineages that evolved in Australia and share 'slow' life history traits that are typical of tropical birds. We obtained BMR from 30 of these 'old-endemics' and ten sympatric species of more recently arrived passerine lineages (derived from Afro-Asian origins or introduced by Europeans) with 'faster' life histories. The BMR of 'slow' temperate-breeding old-endemics was indistinguishable from that of new-arrivals and was not lower than the BMR of 'fast' temperate-breeding non-Australian passerines. Old-endemics had substantially smaller clutches and longer maximal life spans in the wild than new arrivals, but neither clutch size nor maximum life span was correlated with BMR. Our results suggest that low BMR in tropical birds is not functionally linked to their 'slow pace of life' and instead may be a consequence of differences in annual thermal conditions experienced by tropical versus temperate species. PMID- 26874839 TI - Sleepwalking. AB - OPINION STATEMENT: Sleepwalking (SW) is a parasomnia, an abnormal behavior occurring during sleep. SW is a non-REM sleep parasomnia, an arousal disorder, like sleep terrors and confusional arousals. SW results from an incomplete arousal from slow-wave sleep, some regions of the cerebral cortex being awake and allowing movement and vision for example and others being asleep, preventing memorization or judgment. Usually, SW is a quiet wandering of a child that occurs rarely (several times a month or a year), requiring no medical advice and treatment. To reassure the family and to secure the environment are the only things to do. However, sometimes, SW can become crippling because of its frequency (several times a week or a night) because of the risks associated with the behavior (going outside, manipulating sharp objects, etc.) or violence (throwing objects, using weapons, etc.) or because of its consequences on everyday quality of life (sleepiness, fatigue, insomnia, anxiety, and depressive symptoms). In these conditions, treatment is required. It first associates sleep hygiene, reduction of alcohol consumption, and interruption of the treatments that could have promoted the episodes and the securing of the environment. The treatment of precipitants inducing sleep fragmentation such as sleep disordered breathing can be beneficial, reducing the number of events. If episodes persist or are too dangerous, medical treatment is needed. No adequate large controlled trial of drugs has yet been conducted in SW so that no medication has been evaluated properly for efficacy or side effects. However, experts in the field use clonazepam. This treatment is in our experience often effective. If inefficacious, antidepressants can also be proposed. Psychotherapy should be associated to improve anxiety and sometimes insomnia. Few published cases have described that deep relaxation, hypnosis, and cognitive behavioral therapy could be effective. PMID- 26874840 TI - Treatment Options in Intractable Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED). AB - OPINION STATEMENT: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a common condition characterized by an irresistible urge to move the legs, concomitant with an unpleasant sensation in the lower limbs, which is typically relieved by movement. Symptoms occur predominantly at rest and prevail in the afternoon or evening. Treatment of patients with RLS/WED is indicated for those patients who suffer from clinically relevant symptoms. The management of mild forms of RLS/WED is mainly based on dopamine agonists (DA) therapy (including pramipexole and ropinirole) and alpha-2-delta calcium-channel ligand. Nevertheless, with passing of time, symptoms tend to become more severe and the patient can eventually develop pharmacoresistance. Furthermore, long-term treatment with dopaminergic agents may be complicated by the development of augmentation, which is defined by an increase in the severity and frequency of RLS/WED symptoms despite adequate treatment. Here, we discuss which are the best therapeutic options when RLS/WED becomes intractable, with a focus on advantages and side effects of the available medications. Prevention strategies include managing lifestyle changes and a good sleep hygiene. Different drug options are available. Switching to longer-acting dopaminergic agents may be a possibility if the patient is well-tolerating DA treatment. An association with alpha-2-delta calcium-channel ligand is another first-line approach. In refractory RLS/WED, opioids such as oxycodone-naloxone have demonstrated good efficacy. Other pharmacological approaches include IV iron, benzodiazepines such as clonazepam, and antiepileptic drugs, with different level of evidence of efficacy. Therefore, the final decision regarding the agent to use in treating severe RLS/WED symptoms should be tailored to the patient, taking into account the symptomatology, comorbidities, the availability of treatment and the history of the disease. PMID- 26874841 TI - Understanding and Managing the Ictal-Interictal Continuum in Neurocritical Care. AB - OPINION STATEMENT: Continuous electroencephalographic (EEG) monitoring has become an invaluable tool for the assessment of brain function in critically ill patients. However, interpretation of EEG waveforms, especially in the intensive care unit (ICU) setting is fraught with ambiguity. The term ictal-interictal continuum encompasses EEG patterns that are potentially harmful and can cause neuronal injury. There are no clear guidelines on how to treat EEG patterns that lie on this continuum. We advocate the following approaches in a step wise manner: (1) identify and exclude clear electrographic seizures and status epilepticus (SE), i.e., generalized spike-wave discharges at 3/s or faster; and clearly evolving discharges of any type (rhythmic, periodic, fast activity), whether focal or generalized; (2) exclude clear interictal patterns, i.e., spike wave discharges, periodic discharges, and rhythmic patterns at 1/s or slower with no evolution, unless accompanied by a clear clinical correlate, which would make them ictal regardless of the frequency; (3) consider any EEG patterns that lie in between the above two categories as being on the ictal-interictal continuum; (4) compare the electrographic pattern of the ictal-incterictal continuum to the normal background and unequivocal seizures (if present) from the same patient; (5) when available, correlate ictal-interictal continuum pattern with other markers of neuronal injury such as neuronal specific enolase (NSE) levels, brain imaging findings, depth electrode recordings, data from microdialysis, intracranial pressure fluctuations, and brain oxygen measurement; and (6) perform a diagnostic trial with preferably a nonsedating antiepileptic drug with the endpoint being both clinical and electrographic improvement. Minimize the use of anesthetics or multiple AEDs unless there is clear supporting evidence from ancillary tests or worsening of the EEG patterns over time, which could indicate possible neuronal injury. PMID- 26874842 TI - Treatment of Edema Associated With Intracerebral Hemorrhage. AB - OPINION STATEMENT: Cerebral edema (i.e., "brain swelling") is a common complication following intracerebral hemorrhage (ICH) and is associated with worse clinical outcomes. Perihematomal edema (PHE) accumulates during the first 72 h after hemorrhage, and during this period, patients are at risk of clinical deterioration due to the resulting tissue shifts and brain herniation. First-line medical therapies for patients symptomatic of PHE include osmotic agents, such as mannitol in low- or high-dose bolus form, or boluses of hypertonic saline (HTS) at varied concentrations with or without subsequent continuous infusion. Decompressive craniectomy may be required for symptomatic edema refractory to osmotherapy. Other strategies that reduce PHE such as hypothermia and minimally invasive surgery have shown promise in pilot studies and are currently being evaluated in larger clinical trials. Ongoing basic, translational, and clinical research seek to better elucidate the pathophysiology of PHE to identify novel strategies to prevent edema formation as a next major advance in the treatment of ICH. PMID- 26874843 TI - Evidence suggests vocal production learning in a cross-fostered Risso's dolphin (Grampus griseus). AB - Vocal learning is a rare skill in mammals, and we have limited information about the contexts in which they use it. Previous studies suggested that cetaceans in general are skilled at imitating sounds, but only few species have been studied to date. To expand this investigation to another species and to investigate the possible influence of the social environment on vocal learning, we studied the whistle repertoire of a female Risso's dolphin (Grampus griseus) that was stranded at an early age and was subsequently raised in a group of bottlenose dolphins (Tursiops truncatus). We show that this cross-fostered animal produced vocal signals more akin to those of its Tursiops poolmates than those of Risso's dolphins in the wild. This is one of very few systematic cross-fostering studies in cetaceans and the first to suggest vocal production learning in the Risso's dolphin. Our findings also suggest that social experience is a major factor in the development of the vocal repertoire in this species. PMID- 26874844 TI - A micro-RNA expression signature for human NAFLD progression. AB - BACKGROUND: The spectrum of nonalcoholic fatty liver disease (NAFLD) describes disease conditions deteriorating from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to cirrhosis (CIR) to hepatocellular carcinoma (HCC). From a molecular and biochemical perspective, our understanding of the etiology of this disease is limited by the broad spectrum of disease presentations, the lack of a thorough understanding of the factors contributing to disease susceptibility, and ethical concerns related to repeat sampling of the liver. To better understand the factors associated with disease progression, we investigated by next-generation RNA sequencing the altered expression of microRNAs (miRNAs) in liver biopsies of class III obese subjects (body mass index >=40 kg/m(2)) biopsied at the time of elective bariatric surgery. METHODS: Clinical characteristics and unbiased RNA expression profiles for 233 miRs, 313 transfer RNAs (tRNAs), and 392 miscellaneous small RNAs (snoRNAs, snRNAs, rRNAs) were compared among 36 liver biopsy specimens stratified by disease severity. RESULTS: The abundances of 3 miRNAs that were found to be differentially regulated (miR-301a-3p and miR-34a-5p increased and miR-375 decreased) with disease progression were validated by RT-PCR. No tRNAs or miscellaneous RNAs were found to be associated with disease severity. Similar patterns of increased miR 301a and decreased miR-375 expression were observed in 134 hepatocellular carcinoma (HCC) samples deposited in The Cancer Genome Atlas (TCGA). CONCLUSIONS: Our analytical results suggest that NAFLD severity is associated with a specific pattern of altered hepatic microRNA expression that may drive the hallmark of this disorder: altered lipid and carbohydrate metabolism. The three identified miRNAs can potentially be used as biomarkers to access the severity of NAFLD. The persistence of this miRNA expression pattern in an external validation cohort of HCC samples suggests that specific microRNA expression patterns may permit and/or sustain NAFLD development to HCC. PMID- 26874845 TI - Inhibitory Effects of Triptolide on Human Liver Cytochrome P450 Enzymes and P Glycoprotein. AB - BACKGROUND AND OBJECTIVES: Triptolide is an active component derived from Tripterygium wilfordii and it possesses numerous pharmacological activities. However, it remains unclear how triptolide influences the activity of human liver cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). METHODS: In this study, the inhibitory effects of triptolide on the eight human liver CYP isoforms (i.e., 1A2, 3A4, 2A6, 2E1, 2D6, 2C9, 2C19, and 2C8) were investigated in vitro using human liver microsomes (HLMs), and the effects of triptolide on the activity of P gp were investigated using a rhodamine-123 uptake assay. RESULTS: The results showed that triptolide inhibited the activity of CYP1A2 and CYP3A4, with 50 % inhibitory concentration (IC50) values of 14.18 and 8.36 MUM, respectively, but that other CYP isoforms were not affected. Enzyme kinetic studies showed that triptolide was not only a non-competitive inhibitor of CYP1A2, but also a competitive inhibitor of CYP3A4, with inhibition constant (K i) values of 7.32 and 5.67 MUM, respectively. In addition, triptolide is a time-dependent inhibitor for CYP1A2, and the concentration at 50 % maximum inactivation (K I) and maximum inactivation (K inact) values were 286.5 MUM and 0.024 min-1, respectively. The rhodamine-123 uptake assay showed that triptolide could not affect the activity of P-gp. CONCLUSIONS: The in vitro studies of triptolide with CYP isoforms and P gp indicate that triptolide has the potential to cause pharmacokinetic drug interactions with other co-administered drugs metabolized by CYP1A2 and CYP3A4. Further clinical studies are needed to evaluate the significance of this interaction. PMID- 26874847 TI - A Qualitative Study on the Interconnected Nature of HIV, Water, and Family. AB - Human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) and poor access to water are two primary global health issues. Poor access to water may significantly affect families infected with HIV and result in adverse social and health consequences. A qualitative study used semi-structured interviews to understand health and social outcomes of families after the implementation of water interventions in rural Kenya. One major sub-theme emerged during this research, which included the effects of water on an HIV-affected family. Prior to the water interventions, common adverse health effects from lack of nutrition, water, and poor hygiene were experienced. After receiving access to water, nutrition and hygiene were improved and additional time was gained and used to reinforce relationships and spread awareness about HIV/AIDS. This study provides need-based evidence for access to safe drinking water in order to decrease adverse health outcomes and improve the quality of life for HIV-affected individuals. PMID- 26874846 TI - Patterns and Correlates of Serostatus Disclosure to Sexual Partners by Perinatally-Infected Adolescents and Young Adults. AB - Similar to same-age peers, perinatally HIV-infected (PHIV+) youth in the US are engaging in sex, including condomless sex. Understanding decisions about serostatus disclosure to sexual partners is important to domestic and global HIV prevention efforts, since large numbers of PHIV+ children are entering adolescence and becoming sexually active. Using Social Action Theory (SAT) to inform variable selection, we examined correlates of disclosure among 98 PHIV+ adolescents/young adults in New York City. Over half of these youth reported not disclosing to any casual partners (59 %) or to any partners when using condoms (55 %). In bivariate analyses, increased disclosure was associated with older age; being female; earlier age of learning one's serostatus; and increased STD knowledge, disclosure intentions, and parent-child communication. Multiple regression analyses revealed a strong fit with the SAT model. As with adults, disclosure to sexual partners is difficult for PHIV+ youth and challenges prevention efforts. Effective interventions that help youth with disclosure decisions are needed to curb the epidemic. PMID- 26874848 TI - HIV and Elevated Mental Health Problems: Diagnostic, Treatment, and Risk Patterns for Symptoms of Depression, Anxiety, and Stress in a National Community-Based Cohort of Gay Men Living with HIV. AB - People living with HIV (PLHIV) have almost double the risk of depression than the rest of the population, and depression and anxiety among PLHIV have been linked with greater disease progression and other physical health problems. Studies to date, however, have focused almost exclusively on depression or general mental health. Much less research has investigated predictors of anxiety and generalized stress among HIV-positive gay men. This paper reports findings from a national community-based sample of 357 HIV-positive Australians gay men aged 18 years and older. Participants reported elevated rates of depression, anxiety, and generalized stress symptoms. A significant proportion of men with elevated depression and anxiety symptoms were not receiving treatment or had not been diagnosed. Risk factors for elevated mental health concerns included experiences of internalized stigma and discrimination. Anxiety was also associated with lower T-cell CD4 counts. A key protective factor was access to social support. The type of support, in particular emotional support, was found to be more important than the source of support. Our findings suggest that greater emphasis is needed on mental health screening and the provision of emotional support for PLHIV. PMID- 26874849 TI - Standardization and Regulation of Allergen Products in the European Union. AB - Product-specific standardization is of prime importance to ensure persistent quality, safety, and efficacy of allergen products. The regulatory framework in the EU has induced great advancements in the field in the last years although national implementation still remains heterogeneous. Scores of methods for quantification of individual allergen molecules are developed each year and also the challenging characterization of chemically modified allergen products is progressing. However, despite the unquestionable increase in knowledge and the subsequent improvements in control of quality parameters of allergen products, an important aim has not been reached yet, namely cross-product comparability. Still, comparison of allergen product potency, either based on total allergenic activity or individual allergen molecule content, is not possible due to a lack of standard reference preparations in conjunction with validated standard methods. This review aims at presenting the most recent developments in product specific standardization as well as activities to facilitate cross-product comparability in the EU. PMID- 26874850 TI - Classification of Food Allergens and Cross-Reactivity. AB - Patients with specific food allergies are commonly sensitized to related foods, for example, shrimp with other shellfish and peanut with other legumes. In some instances, this represents a true allergy to the related food, defined as cross reactivity, while in other instances, it represents a positive skin or IgE test only, in a patient who can eat the related food without difficulty. This is defined as cross-sensitization. It is extremely important that the clinician recognize these patterns of cross-sensitization and cross-reactivity, both to counsel patients on foods that should be avoided and to make sure that foods are not unnecessarily restricted from the diet. In fact, it is very common for patients to be instructed to avoid entire food groups based just on positive tests, which leads to unnecessary dietary restrictions with effects on food choices, nutrition, and quality of life. PMID- 26874851 TI - Expression of ROR1 has prognostic significance in triple negative breast cancer. AB - Overexpression of receptor tyrosine kinase-like orphan receptor (ROR1) in a variety of human malignancies is associated with aggressive behaviour. Therapeutic agents targeting ROR1 have shown promising results in vivo and in vitro studies. In breast cancer, high-level expression of ROR1 mRNA is associated with high-grade tumours and metastasis. We investigated the prevalence and prognostic significance of ROR1 expression in triple negative breast cancer (TNBC). ROR1 was immunohistochemically stained on full-face sections of 210 TNBC patient samples. Forty-seven TNBC cases (22.4 %) showed strong ROR1 expression, which was associated with shorter disease-free survival (DFS; P = 0.00015), distant metastasis-free survival (DMFS; P = 0.00013) and overall survival (OS; P = 0.026) in univariate analyses. Results were confirmed by multivariate analysis. Seventy TNBC cases (33.3 %) with medullary features showed longer OS (P = 0.00013). We divided the whole series into two subgroups based on the presence or absence of medullary features. Strong ROR1 expression retained a predictive value of shorter DFS and DMFS in both subgroups. Our study suggests that strong ROR1 expression might be an independent adverse prognostic factor in TNBC patients and may serve as a potential marker for patient selection in ROR1-targeted therapy. More large-scale studies are needed to clarify its potential usefulness. PMID- 26874854 TI - Mebendazole crystal forms in tablet formulations. An ATR-FTIR/chemometrics approach to polymorph assignment. AB - Structural polymorphism of active pharmaceutical ingredients (API) is a relevant concern for the modern pharmaceutical industry, since different polymorphic forms may display dissimilar properties, critically affecting the performance of the corresponding drug products. Mebendazole (MEB) is a widely used broad spectrum anthelmintic drug of the benzimidazole class, which exhibits structural polymorphism (Forms A-C). Form C, which displays the best pharmaceutical profile, is the recommended one for clinical use. The polymorphs of MEB were prepared and characterized by spectroscopic, calorimetric and microscopic means. The polymorphs were employed to develop a suitable chemometrics-assisted sample display model based on the first two principal components of their ATR-FTIR spectra in the 4000-600 cm(-1) region. The model was internally and externally validated employing the leave-one-out procedure and an external validation set, respectively. Its suitability for revealing the polymorphic identity of MEB in tablets was successfully assessed analyzing commercial tablets under different physical forms (whole, powdered, dried, sieved and aged). It was concluded that the ATR-FTIR/PCA (principal component analysis) association is a fast, efficient and non-destructive technique for assigning the solid-state forms of MEB in its drug products, with minimum sample pre-treatment. PMID- 26874852 TI - Antiglycation and cell protective actions of metformin and glipizide in erythrocytes and monocytes. AB - Chronic hyperglycaemia causes glycation which subsequently results in the long term complications of diabetes. Albumin, the major plasma protein is more sensitive to glycation resulting in structural, biological and physiological modifications. The long-term benefits of commonly used anti-diabetic drugs such as metformin and glipizide in diabetic patients are well understood. However, no extensive study has been performed to assess their role in the glycation induced albumin modifications and cellular protection. We carried out the glycation of bovine serum albumin using methylglyoxal as a glycating agent in absence or presence of metformin and glipizide to establish their anti-glycation action. Different glycation markers (fructosamine, carbonyl groups, free thiol groups and beta-amyloid aggregation) and protein structural markers (absorption spectroscopy and native-polyacrylamide gel electrophoresis) were examined. Further THP-1 cells (monocytes) and erythrocytes were treated with drugs that were exposed to glycated albumin samples for 24 h, respectively at 37 degrees C to investigate the cytoprotective actions of drugs against glycation. After the treatment different anti-oxidant indices (catalase, glutathione, superoxide dismutase and nitric oxide), cell viability, lipid peroxidation and erythrocyte hemolysis were determined. Treatment with metformin and glipizide during in vitro albumin glycation significantly reduced the formation of glycation adducts and inhibited structural modifications. They restored the level of antioxidants in THP-1 and erythrocytes cells treated with glycated albumin thus protecting cells. Our results suggested protection mode of albumin glycation through inhibition by metformin and glipizide. Additionally, they exerted inhibitory actions on glycation-induced cellular damage by restoring cellular antioxidant defense. PMID- 26874853 TI - First molecular diagnosis of Donohue syndrome in Africa: novel unusual insertion/deletion mutation in the INSR gene. AB - Donohue syndrome (DS) is a very rare autosomal recessive disease affecting less than one in a million life births. It represents the most severe form of insulin resistance due to mutations involving the insulin receptor (IR) gene "INSR". DS is characterized by pre- and postnatal growth retardation with failure-to-thrive, lipoatrophy, acanthosis nigricans, hypertrichosis, and dysmorphic features. An exhaustive INSR gene sequencing was performed after PCR amplification of coding exons and introns boundaries. Bioinformatic tools, including ESEfinder, MFOLD and Proter software were also used to predict the impact of INSR mutation on INSR on gene expression as well as on the protein structure and function. The results have shown a novel unusual c.3003_3012delinsGGAAG (p.S1001_D1004delinsRE) insertion/deletion (indel) mutation within the exon 16 in the three patients, which represent the fourth indel mutation within the INSR gene. The mutation modifies the secondary structure of DNA and RNA, as well as the composition of exonic splicing enhancers of exon 16. Moreover, despite the conservation of the secondary structure of the IR, the p.S1001_D1004delinsRE in-frame mutation is accompanied by the loss of four amino acids replaced by two residues of different nature and hydrophobicity level in the juxtamembrane domain of the receptor. The results have confirmed the role of the juxtamembrane domain of IR involved in a crucial interaction of the IR with cellular effectors essentially the IR substrate 1 (IRS-1), the SHC and the Nck proteins that ensure the signal mediated by the insulin transduction pathway in target cells. Our findings have also proven the genotype/phenotype correlation between INSR mutation and DS phenotype severity. PMID- 26874855 TI - Evaluation of the GHRH-arginine retest for young adolescents with childhood-onset GH deficiency. AB - OBJECTIVE: Retesting of adolescents with childhood-onset GH deficiency (GHD) is recommended, but age-related reference data are scarce. We aimed to establish a cut-off value for the GHRH-arginine test (GHRH+ARG) at the typical age of retesting at near-adult height. DESIGNS: We retrospectively studied 149 patients (108 males) with childhood-onset GHD aged 16.8 +/- 1.7 years (mean +/- SD) with a BMI of 20.9 +/- 3.5 kg/m(2) who had received GHRH+ARG in one single center during 8 consecutive years. Based on the IGF-I serum concentration falling below -2 SDS when off GH, 22 patients suffered from severe GHD of adulthood while 122 were GH sufficient. Five patients could not be determined definitively. GH and IGF-I were measured by in-house RIAs. IGF-I values were transformed into age-related SDS values. ROC-analysis was used to determine the cut-off value. RESULTS: For GHRH+ARG, a cut-off limit of 15.9 ng/ml had the highest pair of sensitivity (91%) and specificity (88%). GH peaks of the patients with a normal BMI between -1 and 0 SDS were higher than those with a high BMI >1 SDS (p<0.01). CONCLUSIONS: When retesting adolescents at near-adult height for severe GHD of adulthood, a GH value of <15.9 ng/ml in GHRH+ARG is discriminatory with good accuracy. Conversion factors for other GH assays in use are provided. A rational decision for or against the continuation of GH therapy into adulthood can be made based on the clinical history of the patient and the combination of the GHRH+ARG retest result and the IGF-I serum concentrations when off GH. PMID- 26874856 TI - The efficacy, tolerability and safety of levetiracetam therapy in a pediatric population. AB - PURPOSE: The purpose of this study was to assess the efficacy and safety of levetiracetam monotherapy in a pediatric population. METHOD: A retrospective review was performed of the charts of 351 consecutive children who were 6 months to 18 years of age and were treated with levetiracetam. Levetiracetam monotherapy was initiated and dosed to efficacy or unacceptable side effects, with a range of 10-112 mg/kg/day. Electroencephalographic examination was performed at pre treatment and 12th months in the post-treatment period. Following the commencement of levetiracetam treatment, the retention rate at 3, 6 and 12 months was 100%, 75% and 57%, respectively. RESULTS: The monotherapy retention rate at 3 and 12 months following the commencement of levetiracetam treatment was (231/351, 66%), and (126/200, 63%) respectively. A total of 165 (47%) patients had idiopathic epilepsy and 186 patients (53%) had symptomatic-cryptogenic epilepsy. The >90% seizure reduction rate was 65%, and the 50-90% seizure reduction rate was 14% at the 3rd month of treatment. Similarly, the >90% seizure reduction rate was 63%, and the 50-90% seizure reduction rate was 15% at the 12th month of treatment. EEG improvement (normalization of EEG) was observed in 65 (47%) patients. Overall, 61 (17%) patients showed adverse events. The most reported side effects were irritability (67%), hyperactivity (8%), somnolence (6%), behavioral disorders (5%), restlessness (5%), increased seizure frequency (3%), enuresis (2%), headache (2%) and attempted suicide (2%). CONCLUSION: The retrospective study of 231 consecutive pediatric patients to confirm that levetiracetam is effective as initial monotherapy for different types of seizures and/or epilepsy syndromes. However there is still a need for well-designed trials to justify the widespread use of levetiracetam monotherapy in children with specific epilepsy syndromes. PMID- 26874857 TI - Predictors of 6-month and 3-year outcomes after psychological intervention for psychogenic non epileptic seizures. AB - PURPOSE: To determine outcome and its predictors following psychological intervention in people with Psychogenic Non-Epileptic Seizures (PNES) METHODS: Prospective audit of 89 consecutive patients. PNES were recorded at baseline (initial psychology appointment), at 6 months and 3 years post the initial appointment. Six-month data was obtained by face-to-face interview, while 3-year data was obtained by contacting general practitioners and by postal survey. RESULTS: Eight patients had stopped having PNES at the first appointment and were discharged. At 6-month follow up 43/81 patients (53.1%) were free of seizures. Predictors of cessation of seizures were: patient employed (OR 4.48, p=0.004), short waiting time for intervention (OR 0.94, p=0.018), the patient feeling they had some control over the seizures (OR 3.30, p=0.021), and an internal locus of control ((OR 7.46, p=0.001). Outcomes at 3 years based on patient report were available in 32/81 patients (36%). 11/32 patients reported being free of seizures. 50/65 patients were not accessing any healthcare for seizures. There were no significant predictors of either outcome among the variables collected. CONCLUSION: Just over half of our patients reported being free of seizures following intervention. Being employed predicted good outcome, but the best predictor of being seizure free at 6 months was having an internal locus of control. This may be useful practically and requires further study. No good predictors of long-term outcome were found, possibly because of loss to follow up. PMID- 26874858 TI - Misdiagnosis in JME: Still a problem after 17 years? AB - PURPOSE: Juvenile myoclonic epilepsy (JME) is one of the most common and recognizable idiopathic generalized epilepsy with its characteristic clinical and EEG features. We think despite the well defined diagnostic criteria, and increasing awareness, misdiagnosis in JME may still be a problem. The present study aims to determine misdiagnosis in JME and to compare the results with our previous study reported in 1998. METHODS: Two hundred JME patients examined at epilepsy outpatient clinics of Bakirkoy Prof. Dr. Mazhar Osman Training and Research Hospital for Psychiatric, Neurologic and Neurosurgical Diseases between the years 2014-2015 were enrolled. Medical records of all patients were evaluated retrospectively; demographical, clinical and electrophysiological data and causes of misdiagnosis were collected from chart reviews. RESULTS: Of 200 JME patients, 49 were misdiagnosed at first medical evaluation. The most common presenting seizure types were generalized tonic clonic seizure and myoclonia in misdiagnosed patients and correctly diagnosed patients, respectively. EEG revealed generalized spike wave and polyspike-wave discharges in 52% of the misdiagnosed patients. Unfortunately the physician was a neurologist in 87.8% of cases with misdiagnoses. Nearly half of 49 misdiagnosed patients were prescribed an inappropriate antiepileptic drug, and the other half were prescribed none. CONCLUSIONS: Comparing our new results with the ones in 1998, misdiagnosis rate was less and time to put a correct diagnosis was shorter. However, proper diagnosis at first sight is still a problem among neurologists even the typical EEG changes are present. PMID- 26874859 TI - Select Bcl-2 antagonism restores chemotherapy sensitivity in high-risk neuroblastoma. AB - BACKGROUND: Pediatric patients with high-risk neuroblastoma (HR NB) often fail to respond to upfront intensive multimodal therapy. Tumor-acquired suppression of apoptosis contributes to therapy resistance. Many HR NB tumors depend on the anti apoptotic protein Bcl-2 for survival, through Bcl-2 sequestration and inhibition of the pro-apoptotic protein, Bim. Bcl-2 dependent xenografts derived from aggressive human NB tumors are cured with a combination of cyclophosphamide and ABT-737, a Bcl-2/Bcl-XL/Bcl-w small molecule antagonist. The oral analogue to ABT 737, Navitoclax (ABT-263), clinically causes an immediate drop in peripheral platelet counts as mature platelets depend on Bcl-xL for survival. This led to the creation of a Bcl-2 selective inhibitor, ABT-199 (Venetoclax). A Phase I trial of ABT-199 in CLL showed remarkable antitumor activity and stable patient platelet counts. Given Bcl-XL does not play a role in HR NB survival, we hypothesized that ABT-199 would be equally potent against HR NB. METHODS: Cytotoxicity and apoptosis were measured in human derived NB cell lines exposed to ABT-199 combinations. Co-Immunoprecipitation evaluated Bim displacement from Bcl-2, following ABT-199. Murine xenografts of NB cell lines were grown and then exposed to a 14-day course of ABT-199 alone and with cyclophosphamide. RESULTS: Bcl-2 dependent NB cell lines are exquisitely sensitive to ABT-199 (IC50 1.5-5 nM) in vitro, where Mcl-1 dependent NBs are completely resistant. Treatment with ABT-199 displaces Bim from Bcl-2 in NB to activate caspase 3, confirming the restoration of mitochondrial apoptosis. Murine xenografts of Mcl-1 and Bcl-2 dependent NBs were treated with a two-week course of ABT-199, cyclophosphamide, or ABT-199/cyclophosphamide combination. Mcl-1 dependent tumors did not respond to ABT-199 alone and showed no significant difference in time to tumor progression between chemotherapy alone or ABT-199/cyclophosphamide combination. In contrast, Bcl-2 dependent xenografts responded to ABT-199 alone and had sustained complete remission (CR) to the ABT-199/cyclophosphamide combination, with one recurrent tumor maintaining Bcl-2 dependence and obtaining a second CR after a second course of therapy. CONCLUSION: HR NB patients are often thrombocytopenic at relapse, raising concerns for therapies like ABT-263 despite its HR NB tumor targeting potential. Our data confirms that Bcl-2 selective inhibitors like ABT-199 are equally potent in HR NB in vitro and in vivo and given their lack of platelet toxicity, should be translated into the clinic for HR NB. PMID- 26874860 TI - Selection and use of pectinolytic yeasts for improving clarification and phenolic extraction in winemaking. AB - Pectinase enzymes have shown a considerable influence in both, sensitive and technological properties of wines. They can help to improve clarification process, releasing more color and flavor compounds entrapped in grape skin, facilitating the liberation of phenolic compounds. This work aims to find yeasts that, because of their native pectinases, can be applied on combined fermentations with Saccharomyces cerevisiae obtaining significant benefits over single-inoculated traditional fermentations. 462 yeast strains isolated from wineries were identified and tested for several enzymatic activities of recognized interest for enology industry. Considering the 7 identified species, only Aureobasidium pullulans, Metschnikowia pulcherrima and Metschnikowia fructicola showed polygalacturonase activity. Because of its interest in winemaking, due to its reported incidence in wine flavor, the impact of M. pulcherrima as a source of pectinolytic enzymes was analyzed by measuring its influence in filterability, turbidity and the increase on color, anthocyanin and polyphenol content of wines fermented in combination with S. cerevisiae. Among the strains screened, M. pulcherrima NS-EM-34 was selected, due to its polygalacturonase activity, for further characterization in both, laboratory and semi-industrial scale assays. The kinetics concerning several metabolites of enological concern were followed during the entire fermentation process at microvinification scale. Improved results were obtained in the expected parameters when M. pulcherrima NS-EM-34 was used, in comparison to wines fermented with S. cerevisiae alone and combined with other pectinolytic and non pectinolytic yeasts (A. pullulans and Lachancea thermotolerans, respectively), even working better than commercial enzymes preparations in most parameters. Additionally, M. pulcherrima NS-EM-34 was used at a semi-industrial scale combined with three different S. cerevisiae strains, confirming its potential application for red wine improvement on the mentioned sensorial and technological properties. PMID- 26874861 TI - Application of ultrasound in combination with heat and pressure for the inactivation of spore forming bacteria isolated from edible crab (Cancer pagurus). AB - This research was performed to characterize the resistance of three different bacterial spore species isolated from pasteurized edible crab (Cancer pagurus) meat to heat treatments and to assess the potential of manosonication (MS) and manothermosonication (MTS) as an alternative for their inactivation. The spore forming bacteria used in this study were Bacillus mycoides, Bacillus weihenstephanensis and Psychrobacillus psychrodurans. The thermal resistance of these three species was determined at different temperatures ranging from 80 to 110 degrees C and their resistance to ultrasound under pressure from 35 to 95 degrees C. Ginafit Excel tool was used to fit the Geeraerd's 'Log-linear + shoulder' and Bigelow & Easty's equations to the survival curves for heat and MS/MTS treatments. From the results obtained it can be concluded that the profile of the survival curves either for heat or for ultrasound treatments depended on the bacterial spore species. When shoulders were detected in the inactivation curves for heat they were also present in the curves for MS/MTS treatments, although the application of an ultrasonic field reduced the shoulder length. B. weihenstephanensis was found to be the most resistant species to heat, requiring 1.4 min to reduce 4log10 cycles at 107.5 degrees C (zT=7.1 degrees C) while B. mycoides was the most sensitive requiring 1.6 min at 95 degrees C (zT=9.1 degrees C). By contrast, B. mycoides was the most resistant to MS. The efficiency of the combination of ultrasonic waves under pressure with heat (MTS) for bacterial spore inactivation was directly correlated with the thermal resistance. Indeed, MTS showed a synergistic effect for the inactivation of the three spores. The highest percentage of synergism corresponded to the spore species with higher zT value (B. mycoides), but the highest temperature at which this synergism was detected corresponded to the most heat tolerant spore species (B. weihenstephanensis). This study revealed that MTS treatment is capable of inactivating spore-forming bacteria and that the inactivation efficiency of the combined treatment is correlated with the thermal resistance of the spore species. PMID- 26874862 TI - Evaluation of high hydrostatic pressure inactivation of human norovirus on strawberries, blueberries, raspberries and in their purees. AB - Human norovirus (HuNoV) has been an increasing concern of foodborne illness related to fresh and frozen berries. In this study, high hydrostatic pressure (HHP) inactivation of HuNoV on fresh strawberries, blueberries, and raspberries and in their purees was investigated. Porcine gastric mucin (PGM)-conjugated magnetic beads (PGM-MBs) and real-time reverse transcriptional polymerase chain reaction (RT-qPCR) were utilized for infectious HuNoV discrimination and quantification. Strawberry puree inoculated with HuNoV genogroup I.1 (GI.1) strain was HHP-treated at 450, 500 and 550 MPa for 2 min each at initial sample temperatures of 0, 4 and 20 degrees C. HuNoV GI.1 strain became more sensitive to HHP treatment as the temperature decreased from 20 to 0 degrees C. HuNoV GI.1 or genogroup II.4 (GII.4) strains were inoculated into three types of berries and their purees and treated at pressure levels from 250 to 650 MPa for 2 min at initial sample temperature of 0 degrees C. For the purees, the HHP condition needed to achieve >2.9 log reduction of HuNoV GI.1 strain and >4.0 log reduction of HuNoV GII.4 strain was found to be >= 550 MPa for 2 min at 0 degrees C. HHP treatment showed better inactivation effect of HuNoV on blueberries than on strawberry quarters and raspberries. HuNoV GI.1 strain was more resistant to HHP treatment than HuNoV GII.4 strain under different temperatures and environment. The physical properties and sensory qualities of HHP-treated and untreated blueberries and the three types of berry purees were evaluated. Color, pH and viscosity of blueberries and three berry purees showed no or slight changes after HHP treatment. Sensory evaluation demonstrated that HHP treatment of 550 MPa for 2 min at 0 degrees C did not significantly reduced the sensory qualities of three berry purees. The results demonstrated that the HHP treatment of 550 MPa for 2 min at 0 degrees C could be a potential nonthermal intervention for HuNoV in berry purees without adversely affecting their sensory qualities and physical properties. PMID- 26874863 TI - Development of spoilage bacterial community and volatile compounds in chilled beef under vacuum or high oxygen atmospheres. AB - Research into microbial community development and metabolism is essential to understand meat spoilage. Recent years have seen the emergence of powerful molecular techniques that are being used alongside conventional microbiology approaches. This enables more accurate studies on meat spoilage. The aim of this study was to investigate the influence of packaging (under vacuum and in high oxygen atmosphere) on the development of microbial communities and metabolic activities at 6 degrees C by using culture-dependent (cultivation, ribotyping) and culture-independent (amplicon sequencing) methods. At the beginning of shelf life, the microbial community mostly consisted of Carnobacterium and Lactobacillus. After two weeks of storage, Lactococcus and Lactobacillus were the dominant genera under vacuum and Leuconostoc in high oxygen meat packages. This indicates that oxygen favoured the genus Leuconostoc comprising only heterofermentative species and hence potential producers of undesirable compounds. Also the number of volatile compounds, such as diacetyl, 1-octen-3-ol and hexanoic acids, was higher in high oxygen packages than under vacuum packages. The beef in high oxygen atmosphere packaging was detected as spoiled in sensory evaluation over 10 days earlier than beef under vacuum packaging. Leuconostoc gelidum, Lactococcus piscium, Lactobacillus sakei and Lactobacillus algidus were the most common species of bacteria. The results obtained from identification of the isolates using ribotyping and amplicon sequencing correlated, except for L. algidus, which was detected in both types of packaging by amplicon sequencing, but only in vacuum packaged samples using the culture based technique. This indicates that L. algidus grew, but was not cultivable in high oxygen beef using the Nordic Committee on Food Analysis standard method. PMID- 26874865 TI - The social space of empowerment within epilepsy services: The map is not the terrain. AB - Empowerment is now seen as an integral component of holistic practice and service design in healthcare, particularly as it relates to the improvement of quality of life for people with epilepsy. However, the literature suggests that empowerment is a neglected and poorly understood concept by service users and providers alike within epilepsy services. Conceptual ambiguity is a further impediment to its understanding and implementation. Bearing this in mind, a clear definition of empowerment is needed in order to realistically recognize, encourage, and prioritize empowerment as a service design philosophy. Therefore, this paper undertakes a concept analysis of empowerment with reference to epilepsy services. Results indicate that empowerment demands a transformation of consciousness and a readiness to act on this transformation in order to allow people to gain personal power and autonomy over their own life, including the self-management of their condition. With this in mind, a critical reflection on the 'micro' and 'macro' levels of power that exist within epilepsy services is warranted with reference to theoretical principles. In this context although the map is not the terrain, we argue that an educational intervention guided by critical social theory principles has the potential to encourage an understanding of empowerment and 'holds the key' to future advances for its implementation within epilepsy services. PMID- 26874866 TI - Improving upon provider-initiated opt-out prenatal HIV-screening approaches in Sub-Saharan Africa. PMID- 26874864 TI - Interictal epileptiform discharge effects on neuropsychological assessment and epilepsy surgical planning. AB - Both animal research and human research suggest that interictal epileptiform discharges (IEDs) may affect cognition, although the significance of such findings remains controversial. We review a wide range of literature with bearing on this topic and present relevant epilepsy surgery cases, which suggest that the effects of IEDs may be substantial and informative for surgical planning. In the first case, we present a patient with epilepsy with left anterior temporal lobe (TL) seizure onset who experienced frequent IEDs during preoperative neuropsychological assessment. Cognitive results strongly lateralized to the left TL. Because the patient failed performance validity tests and appeared amnestic for verbal materials inconsistent with his work history, selected neuropsychological tests were repeated 6 weeks later. Scores improved one to two standard deviations over the initial evaluation and because of this improvement, were only mildly suggestive of left TL impairment. The second case involves another patient with documented left TL epilepsy who experienced epileptiform activity while undergoing neurocognitive testing and simultaneous ambulatory EEG recording. This patient's verbal memory performance was impaired during the period that IEDs were present but near normal when such activity was absent. Overall, although the presence of IEDs may be helpful in confirming laterality of seizure onset, frequent IEDs might disrupt focal cognitive functions and distort accurate measurement of neuropsychological ability, interfering with accurate characterization of surgical risks and benefits. Such transient effects on daily performance may also contribute to significant functional compromise. We include a discussion of the manner in which IED effects during presurgical assessment can hinder individual patient presurgical planning as well as distort outcome research (e.g., IEDs occurring during presurgical assessment may lead to an underestimation of postoperative neuropsychological decline). PMID- 26874867 TI - Maternal risk factors for abnormal vaginal flora during pregnancy. AB - OBJECTIVE: To determine the prevalence of abnormal vaginal flora during pregnancy and associated maternal risk factors. METHODS: A retrospective study was undertaken of cervicovaginal smears performed on pregnant women at a center in Turin, Italy, between 2000 and 2010. Patients were divided into three groups: women with symptoms of genital infections (G1), asymptomatic women at risk of preterm birth (G2), and asymptomatic women with no risk (G3). Logistic regression models identified variables associated with microorganisms. RESULTS: Among 11 219 samples, 4913 (43.8%) were positive, of which 3783 (77.0%) were positive for a single microorganism. Multivariate analysis for G1 showed positive associations between multiple sexual partners and bacterial vaginosis/Ureaplasma urealyticum, and multiparity with preterm birth and U. urealyticum (P<0.05 for all). In G2, there were significant associations between multiparity with preterm birth and bacterial vaginosis/aerobic vaginitis, and North African origin and bacterial vaginosis/U. urealyticum (P<0.05 for all). In G3, there were associations between little education (<8 years) and bacterial vaginosis/U. urealyticum, multiple sexual partners and bacterial vaginosis/U. urealyticum, and bacterial vaginosis and Eastern European origin and not being married (P<0.05 for all). CONCLUSION: Positive cervicovaginal smears were associated with a particular profile. Testing could be advisable for symptomatic women at any stage of pregnancy, during the first trimester for asymptomatic women at risk of preterm birth, and for some asymptomatic women. PMID- 26874868 TI - Intravaginal practices among HIV-negative female sex workers along the US-Mexico border and their implications for emerging HIV prevention interventions. AB - OBJECTIVE: To describe intravaginal practices (IVPs) among female sex workers (FSWs) who inject drugs in two cities-Tijuana and Ciudad Juarez-on the border between the USA and Mexico. METHODS: Data for a secondary analysis were obtained from interviews conducted as part of a randomized controlled trial in FSWs who injected drugs between October 28, 2008, and May 31, 2010. Eligible individuals were aged at least 18years and reported sharing injection equipment and having unprotected sex with clients in the previous month. Descriptive statistics were used to assess frequency and type of IVPs. Logistic regression was used to assess correlates of IVPs. RESULTS: Among 529 FSWs who completed both surveys, 229 (43.3%) had performed IVPs in the previous 6months. Factors independently associated with IVPs were reporting any sexually transmitted infection in the previous 6months (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.1 3.1; P=0.03), three or more pregnancies (aOR 1.9, 95% CI 1.1-3.2; P=0.02), and having clients who became violent when proposing condom use (aOR 5.8, 95% CI 1.0 34.3; P=0.05), which are all factors related to inconsistent condom use. CONCLUSION: Screening for IVPs could help to identify FSW at increased risk of HIV, and facilitate conversations about specific risk-reduction methods. PMID- 26874869 TI - Facial affect recognition in early and late-stage schizophrenia patients. AB - Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps<.01) and an increased misattribution of emotional meaning to neutral faces. PANSS scores of FEP patients on Depressed factor correlated positively with the accuracy to recognize fearful expressions (r=.473). For the MES group fear recognition correlated positively with negative PANSS factor (r=.498) and recognition of sad and neutral expressions was inversely correlated with disorganized PANSS factor (r=-.461 and r=-.541, respectively). These results provide evidence that a generalized impairment of affect recognition is observed in advanced-stage patients and is not characteristic of the early stages of schizophrenia. Moreover, the finding that anomalous attribution of emotional meaning to neutral faces is observed only in MES patients suggests that an increased attribution of salience to social stimuli is a characteristic of social cognition in advanced stages of the disorder. PMID- 26874870 TI - Childhood trauma as a risk factor for the onset of subclinical psychotic experiences: Exploring the mediating effect of stress sensitivity in a cross sectional epidemiological community study. AB - Childhood trauma is a risk factor for the onset of schizophrenic psychosis. Because the psychosis phenotype can be described as a continuum with varying levels of severity and persistence, childhood trauma might likewise increase the risk for psychotic experiences below the diagnostic threshold. But the impact of stressful experiences depends upon its subjective appraisal. Therefore, varying degrees of stress sensitivity possibly mediate how childhood trauma impacts in the end upon the occurrence of subclinical psychotic experiences. We investigated this research question in a representative community cohort of 1500 participants. A questionnaire, comprising five domains of physical and emotional neglect, as well as physical, emotional, and sexual abuse, was used to assess childhood trauma. Based on different symptoms of subclinical psychotic experiences, we conducted a latent profile analysis (LPA) to derive distinct profiles for such experiences. Path modeling was performed to identify the direct and indirect (via stress sensitivity) pathways from childhood trauma to subclinical psychotic experiences. The LPA revealed four classes - unaffected, anomalous perceptions, odd beliefs and behavior, and combined anomalous perceptions/odd beliefs and behavior, that - except for sexual abuse - were all linked to childhood trauma. Moreover, except for physical abuse, childhood trauma was significantly associated with stress sensitivity. Thus, our results revealed that the pathways from emotional neglect/abuse and physical neglect to subclinical psychotic experiences were mediated by stress sensitivity. In conclusion, we can state that subclinical psychotic experiences are affected by childhood traumatic experiences in particular through the pathway of a heightened subjective stress appraisal. PMID- 26874871 TI - Application of biotic ligand and toxicokinetic-toxicodynamic modeling to predict the accumulation and toxicity of metal mixtures to zebrafish larvae. AB - Predicting the accumulation and toxicity of mixtures of metals to aquatic organisms is a key challenge in ecotoxicological studies. In this study, the accumulation and toxicity of mixed essential (Cu) and nonessential (Cd and Pb) metals in zebrafish larvae exposed to a binary mixture of these elements at environmentally relevant concentrations were predicted using a refined toxicokinetic (TK)-toxicodynamic (TD) model aided with biotic ligand model (BLM) and toxic equivalent factor (TEF) approach. Competitive inhibition and non competitive interaction/inhibition were observed in bio-uptake. Both Pb and Cd behaved as competitive inhibitors of Cu uptake at high Cu concentrations (>0.1 MUM). By contrast, Cu uptake was independent of Cd or Pb when the Cu concentrations were below 10(-7) M. Furthermore, low concentrations of Cu had an adiaphorous effect on Cd or Pb uptake. Cd uptake was inhibited by Pb, and the Pb uptake rates consistently decreased in the presence of Cd. The accumulation processes of Cd-Pb, Cu-Cd, and Cu-Pb were accurately predicted by the BLM-aided TK models. The traditional TD model could successfully predict the toxicity of Cd Pb mixtures, but not those of Cu-Cd or Cu-Pb mixtures. The revised TD model, which considered the possible different killing rates (Kk) above or below the threshold, offered better prediction for the toxicity of Cu-Cd or Cu-Pb mixtures. The overall findings may be of key significance in understanding and predicting metal uptake, accumulation, and toxicity in binary or multiple metal exposure scenarios. PMID- 26874872 TI - Mercury dilution by autochthonous organic matter in a fertilized mangrove wetland. AB - A dated sediment core from a highly-fertilized mangrove wetland located in Cubatao (SE Brazil) presented a negative correlation between mercury (Hg) and organic carbon contents. This is an unusual result for a metal with well-known affinity to organic matter. A dilution of Hg concentrations by autochthonous organic matter explained this observation, as revealed by carbon stable isotopes signatures (delta(13)C). Mercury dilution by the predominant mangrove-derived organic matter counterbalanced the positive influences of algal-derived organic matter and clay contents on Hg levels, suggesting that deleterious effects of Hg may be attenuated. Considering the current paradigm on the positive effect of organic matter on Hg concentrations in coastal sediments and the expected increase in mangrove organic matter burial due to natural and anthropogenic stimulations of primary production, predictions on the influences of organic matter on Hg accumulation in mangrove wetlands deserve caution. PMID- 26874873 TI - Increase in dust storm related PM10 concentrations: A time series analysis of 2001-2015. AB - Over the last decades, changes in dust storms characteristics have been observed in different parts of the world. The changing frequency of dust storms in the southeastern Mediterranean has led to growing concern regarding atmospheric PM10 levels. A classic time series additive model was used in order to describe and evaluate the changes in PM10 concentrations during dust storm days in different cities in Israel, which is located at the margins of the global dust belt. The analysis revealed variations in the number of dust events and PM10 concentrations during 2001-2015. A significant increase in PM10 concentrations was identified since 2009 in the arid city of Beer Sheva, southern Israel. Average PM10 concentrations during dust days before 2009 were 406, 312, and 364 MUg m(-3) (median 337, 269,302) for Beer Sheva, Rehovot (central Israel) and Modi'in (eastern Israel), respectively. After 2009 the average concentrations in these cities during dust storms were 536, 466, and 428 MUg m(-3) (median 382, 335, 338), respectively. Regression analysis revealed associations between PM10 variations and seasonality, wind speed, as well as relative humidity. The trends and periodicity are stronger in the southern part of Israel, where higher PM10 concentrations are found. Since 2009 dust events became more extreme with much higher daily and hourly levels. The findings demonstrate that in the arid area variations of dust storms can be quantified easier through PM10 levels over a relatively short time scale of several years. PMID- 26874874 TI - Mutielemental concentration and physiological responses of Lavandula pedunculata growing in soils developed on different mine wastes. AB - This study aimed to: i) evaluate the accumulation and translocation patterns of potentially hazardous elements into the Lavandula pedunculata and their influence in the concentrations of nutrients; and ii) compare some physiological responses associated with oxidative stress (concentration of chlorophylls (Chla, Chlb and total), carotenoids, and total protein) and several components involved in tolerance mechanisms (concentrations of proline and acid-soluble thiols and total/specific activity of catalase (CAT) and superoxide dismutase (SOD)), in plants growing in soils with a multielemental contamination and non-contaminated. Composite samples of soils, developed on mine wastes and/or host rocks, and L. pedunculata (roots and shoots) were collected in Sao Domingos mine (SE of Portugal) and in a reference area with non-contaminated soils, Corte do Pinto, with the same climatic conditions. Sao Domingos soils had high total concentrations of several hazardous elements (e.g. As and Pb) but their available fractions were small (mainly <5.8 % of the total). Translocation behaviour of elements was not clear according to the physiological importance of the elements. In general, plant shoots from Sao Domingos had the highest elements concentrations, but only As, Mn and Zn reached phytotoxic concentrations. Concentration of Chlb in shoots from Sao Domingos was higher than those from Corte do Pinto. No significant differences were obtained between concentrations of Chla, total protein, proline and acid-soluble thiols in shoots collected in both areas, as well as SOD activity (total and specific) and specific CAT activity. Total CAT activity varied with population being lower in the shoots of the plants from Sao Domingos, but no correlation was obtained between this enzymatic activity and the concentrations of the studied elements in shoots. Lavandula pedunculata plants are able to survive in soils developed on different mine wastes with multielemental contamination and low fertility showing no symptoms (visible and physiological) of phytotoxicity or deficiency. PMID- 26874875 TI - Factors influencing aquatic-to-terrestrial contaminant transport to terrestrial arthropod consumers in a multiuse river system. AB - Emerging aquatic insects are important vectors of contaminant transfer from aquatic to terrestrial food webs. However, the environmental factors that regulate contaminant body burdens in nearshore terrestrial consumers remain largely unexplored. We investigated the relative influences of riparian landscape composition (i.e., land use and nearshore vegetation structure) and contaminant flux via the emergent aquatic insect subsidy on selenium (Se) and mercury (Hg) body burdens of riparian ants (Formica subsericea) and spiders of the family Tetragnathidae along 11 river reaches spanning an urban-rural land-use gradient in Ohio, USA. Model-selection results indicated that fine-scale land cover (e.g., riparian zone width, shrub cover) in the riparian zone was positively associated with reach-wide body burdens of Se and Hg in both riparian F. subsericea and tetragnathid spiders (i.e., total magnitude of Hg and Se concentrations in ant and spider populations, respectively, for each reach). River distance downstream of Columbus, Ohio - where study reaches were impounded and flow through a large urban center - was also implicated as an important factor. Although stable isotope analysis suggested that emergent aquatic insects were likely vectors of Se and Hg to tetragnathid spiders (but not to F. subsericea), emergent insect contaminant flux did not emerge as a significant predictor for either reach-wide body burdens of spider Hg or Se. Improved understanding of the pathways and influences that control aquatic-to-terrestrial contaminant transport will be critical for effective risk management and remediation. PMID- 26874876 TI - Resuspension of sediment, a new approach for remediation of contaminated sediment. AB - Natural events and anthropogenic activities are the reasons of undesirable resuspension of contaminated sediments in aquatic environment. Uncontrolled resuspension could remobilize weakly bound heavy metals into overlying water and pose a potential risk to aquatic ecosystem. Shallow harbours, with contaminated sediments are subjected to the risk of uncontrolled resuspension. Remediation of sediments in these areas cannot be performed by conventional in situ methods (e.g. capping with or without reactive amendment). Ex situ remediation also requires dredging of sediment, which could increase the risk of spreading contaminants. Alternatively, the resuspension technique was introduced to address these issues. The concept of the resuspension method is that finer sediments have a greater tendency to adsorb the contamination. Therefore, finer sediments, believed carry more concentration of contaminants, were targeted for removal from aquatic environment by a suspension mechanism in a confined water column. The objective of this study was to evaluate the feasibility of the resuspension technique as a new approach for remediation of contaminated sediment and a viable option to reduce the risk of remobilization of contaminants in harbours due to an undesirable resuspension event. Unlike the common in situ techniques, the resuspension method could successfully reduce the total concentration of contaminants in almost all samples below the probable effect level (PEL) with no significant change in the quality of overlying water. The results indicated that removal efficiency could be drastically enhanced for metals in sediment with a higher enrichment factor. Moreover, availability of metals (e.g. Cd and Pb) with a high concentration in labile fractions was higher in finer sediments with a high enrichment factor. Consequently, removal of contaminants from sediment through the resuspension method could reduce the risk of mobility and availability of metals under changing environmental conditions. Potential dredging in harbours could be performed safer and more cost-effective afterward. PMID- 26874877 TI - Sterol ratios as a tool for sewage pollution assessment of river sediments in Serbia. AB - In this work, source pollution tracing of the sediments of the Danube River and its tributaries in Serbia was performed using sterol ratios. Improved liquid chromatography-tandem mass spectrometry method, which enabled complete chromatographic separation of four analytes with identical fragmentation reactions (epicoprostanol, coprostanol, epicholestanol and cholestanol), was applied for the determination of steroid compounds (hormones, human/animal and plant sterols). A widespread occurrence of sterols was identified in all analyzed samples, whereas the only detected hormones were mestranol and 17alpha-estradiol. A human-sourced sewage marker coprostanol was detected at the highest concentration (up to 1939 ng g(-1)). The ratios between the key sterol biomarkers, as well as the percentage of coprostanol relative to the total sterol amount, were applied with the aim of selecting the most reliable for distinction between human-sourced pollution and the sterols originated from the natural sources in river sediments. The coprostanol/(cholesterol + cholestanol) and coprostanol/epicoprostanol ratios do not distinguish between human and natural sources of sterols in the river sediments in Serbia. The most reliable sterol ratios for the sewage pollution assessment of river sediments in the studied area were found to be coprostanol/(coprostanol + cholestanol), coprostanol/cholesterol and epicoprostanol/coprostanol. For the majority of sediments, human-derived pollution was determined. Two sediment samples were identified as influenced by a combination of human and natural biogenic sources. PMID- 26874879 TI - Herb-drug interaction of Epimedium extract on the pharmacokinetic of dapoxetine in rats. AB - The aim of study is to develop a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method to investigate the pharmacokinetic interaction of Epimedium extract on the dapoxetine in rats. Experimental rats were divided into the following four parallel groups: (1) dapoxetine alone (10mg/kg, i.v.); (2) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, i.v.); (3) dapoxetine alone (10mg/kg, p.o.); (4) oral administration of Epimedium extract (2g/kg) for 3 consecutive days and on the fourth day dapoxetine was administered (10mg/kg, p.o.). The calibration curves of dapoxetine were acquired over a concentration ranges from 1 to 500ng/mL with the R(2)=0.999. The mean matrix effects and extraction recoveries of dapoxetine at three different concentrations (1, 10, 500ng/mL) ranged from 107.3 to 110.9% and from 25.5 to 28.2% respectively. The interday and intraday relative standard deviation were both <6% while the bias were both <14%. The pharmacokinetic results demonstrated that pretreated with/without Epimedium extract for three consecutive days did not significant alter the pharmacokinetics of dapoxetine in rats. The oral bioavailability of dapoxetine was about 75% in rats. PMID- 26874881 TI - Determination of ferric iron chelators by high-performance liquid chromatography using luminol chemiluminescence detection. AB - Iron is an essential element for higher plants, and its acquisition and transportation is one of the greatest limiting factors for plant growth because of its low solubility in normal soil pHs. Higher plants biosynthesize ferric iron [Fe(III)] chelator (FIC), which solubilizes the iron and transports it to the rhizosphere. A high-performance liquid chromatography (HPLC) post-column method has been developed for the analysis of FICs using the luminol/H2O2 system for chemiluminescence (CL) detection. A size-exclusion column was the most suited in terms of column efficiency and CL detection efficiency. Mixing of the luminol with H2O2 in a post-column reaction was feasible, and a two-pump system was used to separately deliver the luminol and H2O2 solutions. The luminol and H2O2 concentrations were optimized using Fe(III)-EDTA and Fe(III)-citrate (Cit) solutions as analytes. A strong CL intensity was obtained for Fe(III)-Cit when EDTA was added to the luminol solution, probably because of an exchange of Cit with EDTA after separation on the HPLC column; CL efficiency was much higher for Fe(III)-EDTA than for Fe(III)-Cit with the luminol/H2O2 system. The present method can detect minute levels of Fe(III)-FICs; the detection limits of Fe(III) EDTA, Fe(III)-Cit and Fe(III)-nicotianamine were 0.77, 2.3 and 1.1pmol, respectively. PMID- 26874878 TI - High throughput LC-MS/MS method for the simultaneous analysis of multiple vitamin D analytes in serum. AB - Recent studies suggest that vitamin D-deficiency is linked to increased risk of common human health problems. To define vitamin D 'status' most routine analytical methods quantify one particular vitamin D metabolite, 25 hydroxyvitamin D3 (25OHD3). However, vitamin D is characterized by complex metabolic pathways, and simultaneous measurement of multiple vitamin D metabolites may provide a more accurate interpretation of vitamin D status. To address this we developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to analyse multiple vitamin D analytes, with particular emphasis on the separation of epimer metabolites. A supportive liquid liquid extraction (SLE) and LC-MS/MS method was developed to quantify 10 vitamin D metabolites as well as separation of an interfering 7alpha-hydroxy-4-cholesten 3-one (7alphaC4) isobar (precursor of bile acid), and validated by analysis of human serum samples. In a cohort of 116 healthy subjects, circulating concentrations of 25-hydroxyvitamin D3 (25OHD3), 3-epi-25-hydroxyvitamin D3 (3 epi-25OHD3), 24,25-dihydroxyvitamin D3 (24R,25(OH)2D3), 1,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), and 25-hydroxyvitamin D2 (25OHD2) were quantifiable using 220MUL of serum, with 25OHD3 and 24R,25(OH)2D3 showing significant seasonal variations. This high-throughput LC-MS/MS method provides a novel strategy for assessing the impact of vitamin D on human health and disease. PMID- 26874880 TI - Study on the potential application of salivary inorganic anions in clinical diagnosis by capillary electrophoresis coupled with contactless conductivity detection. AB - A capillary electrophoresis approach with capacitively coupled contactless conductivity detection method has been developed for the determination of inorganic metabolites (thiocyanate, nitrite and nitrate) in human saliva. Field amplified sample injection, as a simple sample stacking technique, was used in conjunction for online preconcentration of above inorganic anions. A selective separation for the target anions from other coexisting constituents present in saliva could be obtained within 14min in a 10mmol/L His-90mmol/L HAc buffer (pH 3.70) at the separation voltage of -18kV. The limits of detection and limits of quantification of the three analytes were within the range of 3.1-4.9ng/mL (S/N=3) and 10-16ng/mL (S/N=10), respectively. The average recovery data were in the range of 81-108% at three different concentrations. This method provides a simple, rapid and direct approach for metabolite analyses of nitric oxide and cyanide based on noninvasive saliva sample, which presents a potential fast screening tool for clinical test. PMID- 26874882 TI - The Prevalence and Cross-Sectional Associations of Neuropathic-like Pain Among Older, Community-Dwelling Women with Arthritis. AB - OBJECTIVE: To estimate the prevalence and examine the associations of neuropathic like pain in a community-based sample of older Australian women with arthritis. DESIGN: Population based cross-sectional survey. SETTING: Participants were recruited from the 1946-1951 cohort of the Australian Longitudinal Study of Women's Health. SUBJECTS: . Women with self-reported arthritis (n = 147). METHODS: . Primary outcome measure was self-reported neuropathic-like pain, defined as scores >=12 via the painDETECT screening tool. Descriptive statistics summarized health and socio-demographic characteristics, and comparisons made using student's t-test or Wilcoxon Rank Sum test, and Chi-square tests. Independent health and demographic variables were examined by univariable logistic regression, and significant variables included in multiple variable logistic regression modelling. RESULTS: Thirty-nine women (26.5%) were screened as having neuropathic-like pain. Women with neuropathic-like pain were more likely to have poorer health, worse pain, higher pain catastrophizing, more fatigue, and more depression than women with nociceptive pain. Neuropathic-like pain was significantly associated with higher scores on the SF-MPQ sensory scale and pain catastrophizing scale, and with more medication use. CONCLUSIONS: . Neuropathic-like pain in women with arthritis was common and is associated with greater disability and poorer quality of life. PMID- 26874883 TI - Stereotactic Approach Combined with 3D CT Reconstruction for Difficult-to-Access Foramen Ovale on Radiofrequency Thermocoagulation of the Gasserian Ganglion for Trigeminal Neuralgia. AB - OBJECTIVES: The authors describe a technique that includes a stereotactic approach in the preoperative plan in cases where the foramen ovale is difficult to access for radiofrequency thermocoagulation of the Gasserian ganglion. METHODS: The study included 395 patients for whom three-dimensional computed tomographic reconstruction of the skull base, maxilla, and mandible was conducted before surgery. Accessibility of the foramen ovale was defined using numerical data from the three-dimensional computed tomographic reconstruction images. In those patients for whom accessibility of the foramen ovale was considered difficult, the authors used a stereotactic frame to design an individual operative plan. Adjustments of a single point of data,-that is, a change in X axis, Y axis, or an arc angle-were guided by radiographic fluoroscopy images. After verifying successful cannulation and electroneurophysiology, thermocoagulation targets-especially multiple targets recorded as data on the Z axis of the stereotactic approach-were identified and treated. RESULTS: There were 24 patients who met the predetermined criteria for having a difficult-to access foramen ovales-that is, they had at least two contributing factors and/or involvement of division V1 . Twenty-one of the 24 patients required a single satisfactory puncture; three patients required two to three punctures to successfully access the foramen ovale. There were no permanent complications from the procedure. CONCLUSIONS: The authors conclude that this stereotactic approach combined with three-dimensional computed tomographic reconstruction model can improve the accuracy, safety, and efficiency of percutaneous radiofrequency thermocoagulation in patients with trigeminal neuralgia for whom the foramen ovale is difficult to access. PMID- 26874884 TI - Reduced Short- and Long-Latency Afferent Inhibition Following Acute Muscle Pain: A Potential Role in the Recovery of Motor Output. AB - OBJECTIVE: . Corticomotor output is reduced in response to acute muscle pain, yet the mechanisms that underpin this effect remain unclear. Here the authors investigate the effect of acute muscle pain on short-latency afferent inhibition, long-latency afferent inhibition, and long-interval intra-cortical inhibition to determine whether these mechanisms could plausibly contribute to reduced motor output in pain. DESIGN: . Observational same subject pre-post test design. SETTING: . Neurophysiology research laboratory. SUBJECTS: . Healthy, right-handed human volunteers (n = 22, 9 male; mean age +/- standard deviation, 22.6 +/- 7.8 years). METHODS: . Transcranial magnetic stimulation was used to assess corticomotor output, short-latency afferent inhibition, long-latency afferent inhibition, and long-interval intra-cortical inhibition before, during, immediately after, and 15 minutes after hypertonic saline infusion into right first dorsal interosseous muscle. Pain intensity and quality were recorded using an 11-point numerical rating scale and the McGill Pain Questionnaire. RESULTS: . Compared with baseline, corticomotor output was reduced at all time points (p = 0.001). Short-latency afferent inhibition was reduced immediately after (p = 0.039), and long-latency afferent inhibition 15 minutes after (p = 0.035), the resolution of pain. Long-interval intra-cortical inhibition was unchanged at any time point (p = 0.36). CONCLUSIONS: . These findings suggest short- and long latency afferent inhibition, mechanisms thought to reflect the integration of sensory information with motor output at the cortex, are reduced following acute muscle pain. Although the functional relevance is unclear, the authors hypothesize a reduction in these mechanisms may contribute to the restoration of normal motor output after an episode of acute muscle pain. PMID- 26874886 TI - Eribulin in soft-tissue sarcoma. PMID- 26874885 TI - Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. AB - BACKGROUND: A non-randomised, phase 2 study showed activity and tolerability of eribulin in advanced or metastatic soft-tissue sarcoma. In this phase 3 study, we aimed to compare overall survival in patients with advanced or metastatic soft tissue sarcoma who received eribulin with that in patients who received dacarbazine (an active control). METHODS: We did this randomised, open-label, phase 3 study across 110 study sites in 22 countries. We enrolled patients aged 18 years or older with intermediate-grade or high-grade advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens for advanced disease (including an anthracycline). Using an interactive voice and web response system, an independent statistician randomly assigned (1:1) patients to receive eribulin mesilate (1.4 mg/m(2) intravenously on days 1 and 8) or dacarbazine (850 mg/m(2), 1000 mg/m(2), or 1200 mg/m(2) [dose dependent on centre and clinician] intravenously on day 1) every 21 days until disease progression. Randomisation was stratified by disease type, geographical region, and number of previous regimens for advanced soft-tissue sarcoma and in blocks of six. Patients and investigators were not masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. The study is registered with ClinicalTrials.gov, number NCT01327885, and is closed to recruitment, but treatment and follow-up continue. FINDINGS: Between March 10, 2011 and May 22, 2013, we randomly assigned patients to eribulin (n=228) or dacarbazine (n=224). Overall survival was significantly improved in patients assigned to eribulin compared with those assigned to dacarbazine (median 13.5 months [95% CI 10.9-15.6] vs 11.5 months [9.6-13.0]; hazard ratio 0.77 [95% CI 0.62-0.95]; p=0.0169). Treatment-emergent adverse events occurred in 224 (99%) of 226 patients who received eribulin and 218 (97%) of 224 who received dacarbazine. Grade 3 or higher adverse events were more common in patients who received eribulin (152 [67%]) than in those who received dacarbazine (126 [56%]), as were deaths (10 [4%] vs 3 [1%]); one death (in the eribulin group) was considered treatment-related by the investigators. INTERPRETATION: Overall survival was improved in patients assigned to eribulin compared with those assigned to an active control, suggesting that eribulin could be a treatment option for advanced soft-tissue sarcoma. FUNDING: Eisai. PMID- 26874888 TI - Response of MAPK pathway to iron oxide nanoparticles in vitro treatment promotes osteogenic differentiation of hBMSCs. AB - Iron oxide nanoparticles (IONPs) are generally used in multiple biomedical applications. The tissue repair effect of IONPs had been demonstrated in the previous studies of our group, but the underlying mechanism is unclarified. It is well known that stem cell-based therapies show promising prospect in tissue engineering and regenerative medicine, however, whether IONPs could modulate stem cell fate to promote tissue repair is still unclear. Herein, we found that IONPs could promote osteogenic differentiation of human bone-derived mesenchymal stem cells (hBMSCs) in vitro. To insightfully understand the molecular mechanisms, we performed systematic analyses by use of gene microarray assay and bioinformatics analysis, which revealed that gene expression was widely regulated and classical mitogen-activated protein kinase (MAPK) signal pathway was activated by IONPs treatment. As a result, downstream genes of this pathway were regulated to promote osteogenic differentiation. In summary, the present study elucidates a molecular basis explaining how IONPs effect on hBMSCs, which could have many meaningful impacts for stem cells application in regenerative medicine. PMID- 26874890 TI - Mine waste disposal leads to lower coral cover, reduced species richness and a predominance of simple coral growth forms on a fringing coral reef in Papua New Guinea. AB - A large gold mine has been operating at the Lihir Island Group, Papua New Guinea since 1997. The mine disposes of waste rock in nearshore waters, impacting nearby coral communities. During 2010, 2012 we conducted photographic surveys at 73 sites within 40 km of the mine to document impacts of mining operations on the hard coral communities. Coral communities close to the mine (~2 km to the north and south of the mine) were depaurperate, but surprisingly, coral cover and community composition beyond this range appeared to be relatively similar, suggesting that the mine impacts were limited spatially. In particular, we found mining operations have resulted in a significant decrease in coral cover (4.4% 1.48 km from the disposal site c.f. 66.9% 10.36 km from the disposal site), decreased species richness and a predominance of less complex growth forms within ~2 km to the north and south of the mine waste disposal site. In contrast to the two 'snapshot' surveys of corals performed in 2010 and 2012, long term data (1999 2012) based on visual estimates of coral cover suggested that impacts on coral communities may have been more extensive than this. With global pressures on the world's coral reefs increasing, it is vital that local, direct anthropogenic pressures are reduced, in order to help offset the impacts of climate change, disease and predation. PMID- 26874889 TI - Tissue segregation restores the induction of bone formation by the mammalian transforming growth factor-beta(3) in calvarial defects of the non-human primate Papio ursinus. AB - A diffusion molecular hypothesis from the dura and/or the leptomeninges below that would control the induction of calvarial membranous bone formation by the recombinant human transforming growth factor-beta3 (hTGF-beta3) was investigated. Coral-derived calcium carbonate-based macroporous constructs (25 mm diameter; 3.5/4 mm thickness) with limited hydrothermal conversion to hydroxyapatite (7% HA/CC) were inserted into forty calvarial defects created in 10 adult Chacma baboons Papio ursinus. In 20 defects, an impermeable nylon foil membrane (SupraFOIL((r))) was inserted between the cut endocranial bone and the underlying dura mater. Twenty of the macroporous constructs were preloaded with hTGF-beta3 (125 MUg in 1000 MUl 20 mM sodium succinate, 4% mannitol pH4.0), 10 of which were implanted into defects segregated by the SupraFOIL((r)) membrane, and 10 into non segregated defects. Tissues were harvested on day 90, processed for decalcified and undecalcified histology and quantitative real-time polymerase chain reaction (qRT-PCR). Segregated untreated macroporous specimens showed a reduction of bone formation across the macroporous spaces compared to non-segregated constructs. qRT-PCR of segregated untreated specimens showed down regulation of osteogenic protein-1 (OP-1), osteocalcin (OC), bone morphogenetic protein-2 (BMP-2), RUNX-2 and inhibitor of DNA binding-2 and -3 (ID2,ID3) and up regulation of TGF-beta3, a molecular signalling pathway inhibiting the induction of membranous bone formation. Non-segregated hTGF-beta3/treated constructs also showed non osteogenic expression profiles when compared to non-segregated untreated specimens. Segregated hTGF-beta3/treated 7% HA/CC constructs showed significantly greater induction of bone formation across the macroporous spaces and, compared to non-segregated hTGF-beta3/treated constructs, showed up regulation of OP-1, OC, BMP-2, RUNX-2, ID2 and ID3. Similar up-regulated expression profiles were seen for untreated non-segregated constructs. TGF-beta signalling via ID genes creates permissive or refractory micro-environments that regulate the induction of calvarial bone formation which is controlled by the exogenous hTGF-beta3 upon segregation of the calvarial defects. The dura is the common regulator of the induction of calvarial bone formation modulated by the presence or absence of the SupraFOIL((r)) membrane with or without hTGF-beta3. PMID- 26874891 TI - Limpets compensate sea urchin decline and enhance the stability of rocky subtidal barrens. AB - Understanding the mechanisms that regulate shifts among alternative ecosystems has become a priority for ecologists and environmental scientists. This study assessed the relative importance of different herbivorous invertebrates (urchins and limpets) in regulating transitions from barren to vegetated states on Mediterranean rocky reefs, under different levels of nutrient availability. Nutrient concentration and the herbivore assemblage were manipulated to test i) whether limpets can compensate for the decline or loss of sea urchin populations, thereby contributing to the persistence of barrens, ii) whether limpet effects vary according to nutrient availability and iii) whether limpets affect the structure of the algal assemblage. The complete removal of sea urchins was not sufficient to trigger the recovery of erect and turf-forming macroalgae if limpets were left at natural density, suggesting that these herbivores play an important role in the stability of the barren state. The effect of these mesograzers was particularly important under oligotrophic conditions. This suggests that limpets play an important role in sustaining the stability of the barren state. A more comprehensive assessment of top-down forces, implying the quantification of the relative effect of different herbivore guilds, is therefore necessary to estimate the strength of hysteresis and to identify critical thresholds at which shifts back to the vegetated state are initiated. PMID- 26874887 TI - Spatiotemporal control of cardiac anisotropy using dynamic nanotopographic cues. AB - Coordinated extracellular matrix spatiotemporal reorganization helps regulate cellular differentiation, maturation, and function in vivo, and is therefore vital for the correct formation, maintenance, and healing of complex anatomic structures. In order to evaluate the potential for cultured cells to respond to dynamic changes in their in vitro microenvironment, as they do in vivo, the collective behavior of primary cardiac muscle cells cultured on nanofabricated substrates with controllable anisotropic topographies was studied. A thermally induced shape memory polymer (SMP) was employed to assess the effects of a 90 degrees transition in substrate pattern orientation on the contractile direction and structural organization of cardiomyocyte sheets. Cardiomyocyte sheets cultured on SMPs exhibited anisotropic contractions before shape transition. 48 h after heat-induced shape transition, the direction of cardiomyocyte contraction reoriented significantly and exhibited a bimodal distribution, with peaks at ~45 and -45 degrees (P < 0.001). Immunocytochemical analysis highlighted the significant structural changes that the cells underwent in response to the shift in underlying topography. The presented results demonstrate that initial anisotropic nanotopographic cues do not permanently determine the organizational fate or contractile properties of cardiomyocytes in culture. Given the importance of surface cues in regulating primary and stem cell development, investigation of such tunable nanotopographies may have important implications for advancing cellular maturation and performance in vitro, as well as improving our understanding of cellular development in response to dynamic biophysical cues. PMID- 26874892 TI - Clinically meaningful changes in functional performance resulting from self directed interventions in individuals with arthritis. AB - OBJECTIVES: To examine the clinical meaningfulness of changes observed in functional performance from two self-directed interventions targeting adults with arthritis. STUDY DESIGN: Randomized controlled trial. METHODS: Participants (n = 312) were randomized to a 12-week self-directed exercise or nutrition intervention. Objective measures of functional performance (6-minute walk, seated reach, grip strength, 30-second chair stand, gait speed, balance) were obtained at baseline, 12 weeks, and nine months. Minimally (>=0.20 standard deviation) and substantially (>=0.50) meaningful changes in functional performance were examined. Changes in the percent 'impaired' and at risk for losing independence using established standards, and associations between physical activity and impairment/risk status were also examined. Group * Time interactions were not significant; therefore groups were combined in all analyses. RESULTS: Minimally (31-71%) and substantially (13-54%) meaningful changes in function were shown. There was a significant decrease in the percentage of participants 'impaired' on the 30-second chair stand (both time points) and gait speed (nine months). The percentage of participants at risk for losing independence significantly decreased for the 30-second chair stand (both time points) and the 6-minute walk (nine months). Those engaging in >=2 h of leisure-time physical activity were significantly less likely to be impaired on the 6-minute walk, 30-second chair stand, and gait speed at 12 weeks, and the 6-minute walk at nine months. CONCLUSIONS: Interventions that can slow functional declines, and ideally result in clinically meaningful improvements in functional performance among adults with arthritis are needed. Meaningful improvements in various indicators of functional performance can result from self-directed exercise and nutrition programs. These types of programs have the potential for wide-spread dissemination, and thus broad reach. PMID- 26874893 TI - Eating-Disordered Behaviour in Adolescents with Type 1 Diabetes. AB - OBJECTIVES: To evaluate dysfunctional eating behaviour, self-esteem, social physique anxiety and quality of life in adolescents with type 1 diabetes who have differing desired weights and to evaluate the predictors of dysfunctional eating behaviour in these adolescents, with a focus on personal and psychological variables. METHODS: We evaluated 79 adolescents with type 1 diabetes (mean age of 15.71 years) of both sexes (58.2% females) using the Eating Disorders Examination Questionnaire (EDE-Q), the Rosenberg Self-Esteem Scale (RSES), the Social Physique Anxiety Scale (SPAS-R) and the Diabetes Quality of Life (DQoL) measure. RESULTS: Of the adolescents, 44 with type 1 diabetes reported the desire to maintain or increase their current weight, and 35 reported the desire to reduce their current weight. The participants with the desire to weigh less were mainly females who exercised regularly and demonstrated more frequent binge eating and purging. Additionally, this group exhibited an increased frequency of eating disturbances, such as restraint and eating, weight and shape concerns. Moreover, this group demonstrated increased social physique anxiety and decreased diabetes quality of life in relation to the impact of diabetes, worries about diabetes and satisfaction with life. Finally, predictors of eating disturbances included the desire for lower weight, higher social physique anxiety and lower diabetes related quality of life. CONCLUSIONS: The desire for a lower weight in adolescents with type 1 diabetes may increase problems related to eating behaviour and general quality of life. PMID- 26874894 TI - Lung density associates with survival in alpha 1 antitrypsin deficient patients. AB - INTRODUCTION: CT density correlates with quality of life (QOL) scores and impaired upper zone lung density associates with higher mortality in alpha one antitrypsin deficiency (A1ATD). We hypothesised that decline in CT densitometry would relate to survival or deterioration in QOL in A1ATD. METHODS: All augmentation naive PiZZ patients in the UK A1ATD registry with >= two successive quantitative CT scans were selected. Patients were divided into groups based on CT density decline and the relationship to survival and change in QOL compared by univariate analyses and multivariate Cox regression. Analyses were performed for whole lung, upper zone and lower zone density separately. Exploratory analyses of FEV1 subgroups were conducted. RESULTS: 110 patients were identified; 77 had whole lung and lung zone density recorded on two CT scans, 33 patients had upper zone data only on four scans. Decline in lower zone density associated with survival, even after adjustment for baseline lung density (p = 0.048), however upper zone density and whole lung density decline did not. This difference appeared to be driven by those with FEV1 >30% predicted. CONCLUSION: Rate of change in lung densitometry could predict survival in A1ATD. PMID- 26874895 TI - Validity of transcutaneous PCO2 in monitoring chronic hypoventilation treated with non-invasive ventilation. AB - BACKGROUND: Non-invasive ventilation (NIV) is an efficient treatment for patients with chronic hypercapnic respiratory failure (CRF), but requires regular monitoring to detect both diurnal and nocturnal residual hypercapnia. The present study was designed to determine 1) whether transcutaneous PCO2 (PtcCO2) is a valid tool for monitoring PaCO2 in this group of patients, and 2) if overnight instrumental drift of the PtcCO2 sensor is clinically significant. METHODS: Sixty seven patients with CRF on long term NIV were included. Arterial blood gases (ABG) were sampled from the radial artery during PtcCO2 measurement. PtcCO2 was recorded 2 min after ABG sampling. Instrumental drift was tested by measuring a gas of known CO2 concentration after auto-calibration of the sensor in the evening, and on the following morning. FINDINGS: PaCO2 values ranged from 3.97 kPa to 9.0 kPa. Thirty-six (53%) patients were hypercapnic. Correlation between PaCO2 and PtcCO2 was highly significant (r(2) = 0.9, p < 0.0001), Bias (d) and SD of bias (s) were 0.23 kPa and 0.28 kPa respectively, with a minor underestimation of PaCO2. Limits of agreement (d +/- 2s) were; -0.32; 0.79 kPa. None of the paired values of PaCO2/PtcCO2 had a difference exceeding 1 kPa. The mean drift of PtcCO2 was 0.14 +/- 0.54 kPa/8 h (p = 0.04; 95% CI: 0.01-0.27). INTERPRETATION: With the device tested, in stable patients under NIV-treatment for CRF, PtcCO2 accurately reflects PaCO2. PtcCO2 can be used to monitor CO2 overnight during NIV without any clinically significant drift. TRIAL REGISTRATION N degrees : NCT01845233. PMID- 26874896 TI - Primary school children often underestimate their nasal obstruction. AB - BACKGROUND: No consensus has ever been reached about the correlation between nasal resistance and the subjective sensation of nasal patency. The aim of the present study was to better de ne whether primary school and secondary school aged children correctly estimate their nasal obstruction. MATERIALS AND METHODS: Two hundred eighty four children (168 males and 116 female) aged between 6 and 14 years (9.5+2.9 years) affected by Pediatric Allergic Rhinitis underwent Rhinomanometry and they were considered as correctly estimating their nasal obstruction when the grade of nasal patency corresponded to the severity of the NOSE score, overestimating when the grade of nasal patency was <1 when compared to the severity of the score, underestimating when the grade of nasal patency was >1 when compared to the severity of the score. RESULTS: Correlation between NOSE score and nasal patency was statistically significant (r -0.74; p<0.001). Children between 6 and 9 years of age underestimate (43.7%) and children >12 overestimate (34.7%) their symptoms more frequently than children among other age ranges (p<0.001). CONCLUSION: Although NOSE score approximately allow to quantify nasal obstruction, in children, especially between 6 and 9 years of age, an objective measurement of nasal patency should be performed to better define the therapeutic approach. PMID- 26874897 TI - Medicaid beneficiaries undergoing complex surgery at quality care centers: insights into the Affordable Care Act. AB - BACKGROUND: Medicaid beneficiaries do not have equal access to high-volume centers for complex surgical procedures. We hypothesize there is a large Medicaid Gap between those receiving emergency general vs complex surgery at the same hospital. METHODS: Using the Nationwide Inpatient Sample, 1998 to 2010, we identified high-volume pancreatectomy hospitals. We then compared the percentage of Medicaid patients receiving appendectomies vs pancreatectomies at these hospitals. Hospital characteristics associated with increased Medicaid Gap were evaluated using generalized estimating equation models. RESULTS: A total of 602 hospital-years of data from 289 high-volume pancreatectomy hospitals were included. Median percentages of Medicaid appendectomies and pancreatectomies were 12.1% (interquartile range: 5.8% to 19.8%) and 6.7% (interquartile range: 0% to 15.4%), respectively. Hospitals that performed greater than or equal to 40 pancreatic resections per year had higher odds of having significant Medicaid Gap (odds ratio 2.3, 95% confidence interval 1.1 to 5.0). CONCLUSIONS: Gaps exist between the percentages of Medicaid patients receiving emergency general surgery vs more complex surgical care at the same hospital and may be exaggerated in hospitals with very high volume of complex elective surgeries. PMID- 26874899 TI - Tuberculosis outbreaks: Beyond the tuberculin skin test. PMID- 26874898 TI - Farmer's Lung Disease. A Review. AB - Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality. PMID- 26874900 TI - [Fixed drug eruption secondary due to griseofulvin]. PMID- 26874902 TI - HER2-positive breast cancer: is more treatment better? PMID- 26874904 TI - PKM2 uses control of HuR localization to regulate p27 and cell cycle progression in human glioblastoma cells. AB - The M2 isoform of pyruvate kinase (PK) is upregulated in most cancers including glioblastoma. Although PKM2 has been reported to use dual kinase activities to regulate cell growth, it also interacts with phosphotyrosine (pY)-containing peptides independently of its kinase activity. The potential for PKM2 to use the binding of pY-containing proteins to control tumor growth has not been fully examined. We here describe a novel mechanism by which PKM2 interacts in the nucleus with the RNA binding protein HuR to regulate HuR sub-cellular localization, p27 levels, cell cycle progression and glioma cell growth. Suppression of PKM2 in U87, T98G and LN319 glioma cells resulted in increased p27 levels, defects in entry into mitosis, increased centrosome number, and decreased cell growth. These effects could be reversed by shRNA targeting p27. The increased levels of p27 in PKM2 knock-down cells were caused by a loss of the nuclear interaction between PKM2 and HuR, and a subsequent cytoplasmic re distribution of HuR, which in turn led to increased cap-independent p27 mRNA translation. Consistent with these results, the alterations in p27 mRNA translation, cell cycle progression and cell growth caused by PKM2 suppression could be reversed in vitro and in vivo by suppression of HuR or p27 levels, or by introduction of forms of PKM2 that could bind pY, regardless of their kinase activity. These results define a novel mechanism by which PKM2 regulates glioma cell growth, and also define a novel set of potential therapeutic targets along the PKM2-HuR-p27 pathway. PMID- 26874903 TI - Dispensing behaviour of pharmacies in prescription drug markets. AB - OBJECTIVE: We aim to investigate pharmacies' dispensing behaviour under the existing dispensing regulations in Germany. METHODS: Using administrative data, we performed a cross-sectional retrospective study to analyse whether the competitive environment and pharmacy characteristics, i.e., organisation, lead to dispensing choices aimed at by third-party payers. We specified generalised linear models with the share of imported pharmaceuticals, generic share, and share of preferred brands as dependent variables. RESULTS: The final dataset contained 49,260,902 prescriptions from 16,797 pharmacies. The average share of imported pharmaceuticals across the pharmacies was 18.4% (standard deviation (SD) 8.8), the average generic share was 92.8% (SD 2.1), and compliance with preferred brands was 81.3% (SD 5.9). Pharmacies with little competition used fewer imported pharmaceuticals (p<0.001), generics (p<0.001) and preferred brands (p<0.001); less organised pharmacies yielded similar results. The difference in outcomes between pharmacies in the first and 4th quartiles of the pharmacy organisation variable is 17.4% vs. 17.0% for share of imported pharmaceuticals, 92.8% vs. 92.7% for generic share and 81.9% vs. 81.1% for compliance with preferred brands. CONCLUSION: We show that pharmacies' dispensing choices meet the aims of payers at high levels. However, dispensing behaviour varies between pharmacies. Increasing competition among pharmacies and targeting pharmacies with high shares of bill auditing seem viable options to improving dispensing behaviour as defined by payers. PMID- 26874901 TI - Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo controlled, phase 3 trial. AB - BACKGROUND: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2 positive breast cancer. METHODS: We did this multicentre, randomised, double blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged >=18 years, or >=20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or >=4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. FINDINGS: Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0.67, 95% CI 0.50-0.91; p=0.0091). The 2-year invasive disease-free survival rate was 93.9% (95% CI 92.4-95.2) in the neratinib group and 91.6% (90.0 93.0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 [<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (>=grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. INTERPRETATION: Neratinib for 12 months significantly improved 2 year invasive disease-free survival when given after chemotherapy and trastuzumab based adjuvant therapy to women with HER2-positive breast cancer. Longer follow up is needed to ensure that the improvement in breast cancer outcome is maintained. FUNDING: Wyeth, Pfizer, Puma Biotechnology. PMID- 26874905 TI - Dynamic subcellular localization of estrogen receptor alpha during the first two cleavages of mouse preimplantation embryos. AB - Zygotic gene activation (ZGA) is one of the most important events after mouse fertilization, but the mechanisms underpinning it are still unclear. Estrogen receptor alpha (ERalpha) is a versatile player in animal development. Our preliminary studies showed that ERalpha-specific antagonists blocked mouse 2-cell development and inhibited ZGA related gene expression, indicating an indispensable role of maternal ERalpha in early mouse preimplantation embryo development (PED). Here, we performed immunostaining detection to investigate the cell cycle specific subcellular localization of ERalpha, and serine 118 phosphorylated ERalpha (pERalpha-S118), during the first two cleavages of mouse PED. Our results showed that ERalpha nuclear localization appeared at 1-cell S phase, disappeared at metaphase, and reappeared since the G1 phase of 2-cell embryos. Nuclear expression of pERalpha-S118 started at the 1-cell S-phase, but was absent at the G1 phase of 2-cell embryos, and reappeared since the 2-cell S phase. Interestingly, pERalpha-S118 showed a dynamic expression pattern among nuclear, nuclear surface, cytoplasm and cell membrane. These results indicate that maternal derived ERalpha might still function in the first two cleavages of mouse PED, during which ZGA occurs. PMID- 26874906 TI - Interval aerobic training combined with strength-endurance exercise improves metabolic markers beyond caloric restriction in Zucker rats. AB - AIMS: To investigate the effects of interval aerobic training combined with strength-endurance exercise (IASE) and caloric restriction (CR) on body composition, glycaemic and lipid profile and inflammatory markers. METHODS AND RESULTS: Thirty-two Zucker diabetic fatty rats were randomised into 4 groups (sedentary + CR; sedentary + adlibitum; IASE + CR; and IASE + adlibitum). Training groups conducted an IASE programme in the same session, 5 days/week for 2 months. Body weight, fat and muscle mass and body water were measured using a body composition analyser. Plasma total, LDL and HDL cholesterol, phospholipids, triglycerides, insulin, adiponectin, tumour necrosis factor alpha, interleukin 1 and 10 were measured. Blood fasting and postprandial glucose were assessed. Body weight was lower in the CR compared to the adlibitum groups (p < 0.001). Fat mass was lower in the CR compared to the adlibitum (p < 0.05) and in the IASE compared to the sedentary groups (p < 0.001), but IASE increased lean mass (p < 0.001). Triglycerides were lower in the CR compared to the adlibitum groups (p < 0.001) whereas total and LDL-cholesterol and fasting glucose were reduced only in the IASE groups (all, p < 0.001). Phospholipids decreased in the CR compared to the adlibitum (p < 0.05) and the IASE compared to the sedentary groups (p < 0.001). The area under the curve after oral glucose tolerance test, insulin and homoeostatic model assessment were lower in the IASE and the CR compared to the sedentary and adlibitum groups, respectively (all, p < 0.001). Adiponectin was lower in the CR groups (p < 0.001). CONCLUSION: Overall, IASE as well as CR were both useful interventions, especially when combined. However, IASE showed greater improvements on body composition, inflammatory and glycaemic profile than CR did. PMID- 26874908 TI - [Adenomyomatosis of the gallbladder: A case report]. PMID- 26874907 TI - Neck circumference is associated with carotid intimal-media thickness but not with coronary artery calcium: Results from The ELSA-Brasil. AB - BACKGROUND AND AIMS: It is uncertain whether neck circumference can be a risk indicator for subclinical atherosclerosis. We aimed to investigate their relationships measured by coronary artery calcium (CAC) and common carotid intima media thickness (cc-IMT) with neck circumference in ELSA-Brasil. METHODS AND RESULTS: In cross-sectional and sex-specific analyses of 2266 women (50.6 +/- 8.4 yrs) and 1886 men (50.7 +/- 9.0 yrs) with both cc-IMT and CAC, free from previous cardiovascular disease at baseline, we built logistic models using diverse cut off points for CAC score (0 vs > 0, < 100 vs >= 100, < 400 vs >= 400 Agatston units) and cc-IMT (< 75 th percentile vs >= 75 th; <90th percentile vs >= 90 th) as dependent variables, after which adjustments for age and traditional cardiovascular risk factors were made. Mean neck circumference was 33.6 (+/- 2.4 cm) for women and 38.8 (+/- 2.6 cm) for men. In fully adjusted models including sociodemographic, cardiovascular risk factors and body-mass index and waist circumference, for each 1 standard deviation increase in neck circumference we found an odds ratio (OR, 95% CI) for IMT above the 75th percentile of (1.52, 1.16; 1.99) for women and (1.66, 1.28; 2.14) for men, and above the 90th cc-IMT percentile [1.66 (1.19; 2.32) for men but not for women [1.21 (0.80; 1.82)]. We found no association between neck circumference and CAC using different cut-off points (p > 0.05 for all). CONCLUSION: Neck circumference was significantly and independently associated with cc-IMT but not with CAC in women and men, indicating a possible effect of perivascular fat tissue on atherosclerosis. PMID- 26874909 TI - [Persistant Legionella pneumophila and Enterococcus faecium pulmonary infection: Look for an abscess!]. PMID- 26874910 TI - Evaluation in vitro and in vivo of curcumin-loaded mPEG-PLA/TPGS mixed micelles for oral administration. AB - The aim of this work is to prepare and characterize curcumin-loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelles (CUR-MPP-TPGS-MMs), analyze the influence of formulation on enhancing the solubility of curcumin in water, and evaluate the improvement of intestinal absorption after oral administration. CUR MPP-TPGS-MMs were prepared using the thin film diffusion method and optimized with the uniform design. The optimal CUR-MPP-TPGS-MMs were provided with high drug-loading (16.1%), small size (46.0 nm) and spherical shape. Low critical micelle concentration (CMC) and superior dilution stability showed that CUR-MPP TPGS-MMs could keep integrity during the dilution of gastrointestinal fluid. In vitro drug release study indicated a sustained release of curcumin from CUR-MPP TPGS-MMs in simulated gastrointestinal solution. The absorption mechanism of passive diffusion was obtained by measuring in situ intestinal absorption of CUR MPP-TPGS-MMs in rats, and the best absorption segment was found to be the duodenum. The pharmacokinetics was evaluated in rats at the dose of 75 mg/kg by intragastric administration. The Cmax and mean retention time (MRT0-24) for CUR MPP-TPGS-MMs were both increased, and the relative bioavailability of micelle formulation to curcumin suspension was 927.3%. These results suggested that mPEG PLA/TPGS mixed micelle system (MPP-TPGS-MMs) showed great potential in improving oral bioavailability of curcumin. PMID- 26874911 TI - Dietary pattern, inflammation and cognitive decline: The Whitehall II prospective cohort study. AB - BACKGROUND & AIMS: Low-grade inflammation appears to play an etiological role in cognitive decline. However the association between an inflammatory dietary pattern and cognitive decline has not been investigated. We aimed to investigate dietary patterns associated with inflammation and whether such diet is associated with cognitive decline. METHODS: We analyzed 5083 participants (28.7% women) from the Whitehall II cohort study. Diet and serum interleukin-6 (IL-6) were assessed in 1991-1993 and 1997-1999. We used reduced rank regression methods to determine a dietary pattern associated with elevated IL-6. Cognitive tests were performed in 1997-1999 and repeated in 2002-2004 and 2007-2009. The association between dietary pattern and cognitive decline between ages 45 and 79 was assessed using linear mixed models. RESULTS: We identified an inflammatory dietary pattern characterized by higher intake of red meat, processed meat, peas and legumes, and fried food, and lower intake of whole grains which correlated with elevated IL-6 both in 1991-1993 and 1997-1999. A greater decline in reasoning was seen in participants in the highest tertile of adherence to the inflammatory dietary pattern (-0.37 SD; 95% confidence interval [CI] -0.40, -0.34) compared to those in the lowest tertile (-0.31; 95% CI -0.34, -0.28) after adjustment for age, sex, ethnicity, occupational status, education, and total energy intake (p for interaction across tertiles = 0.01). This association remained significant after multivariable adjustment. Similarly for global cognition, the inflammatory dietary pattern was associated with faster cognitive decline after multivariable adjustment (p for interaction across tertiles = 0.04). Associations were stronger in younger participants (<56 years), reducing the possibility of reverse causation. CONCLUSIONS: Our study found that a dietary pattern characterized as higher intake of red and processed meat, peas, legumes and fried food, and lower intake of whole grains was associated with higher inflammatory markers and accelerated cognitive decline at older ages. This supports the case for further research. PMID- 26874913 TI - A large prospective audit of morbidity and mortality associated with feeding gastrostomies in the community. AB - BACKGROUND & AIMS: Morbidity after 30 days and morbidity after 1 year from gastrostomy placement is poorly characterised as patients are discharged into the community. We prospectively recorded morbidity and mortality associated with gastrostomy placement over a five year period. PATIENTS AND METHODS: Community dietitians regularly reviewed all patients with a gastrostomy after hospital discharge, prospectively recording morbidity and mortality between 2008 and 2012. In addition hospital databases and case notes were examined. Recorded morbidity included insertion site infection, leakage, over granulation, haemorrhage and buried bumper. RESULTS: The commonest indication for PEG placement was following an acute cerebral injury. There were no deaths and few complications directly related to gastrostomy insertion in 350 patients. We collected a total of 571 years of gastrostomy data. Mortality within 30 days was predominantly from a respiratory infection. 30 day, 3 and 12 month cumulative mortality (and morbidity) were 8% (2%), 16% (10%) and 35% (15%) respectively. 38% of patients required treatment for an insertion site infection with 70% of these having further infections. Overall there was a site infection every 2.1 years a gastrostomy was in situ. Complications such as buried bumpers (5(1.4%)), persistent fistulas (0) and over granulation (7(2%)) were rare. Few gastrostomies required replacement (11%). CONCLUSION: We have demonstrated reassuringly low rates of gastrostomy-associated morbidity and mortality. There was no direct mortality. The greatest morbidity resulted from gastrostomy-site infection. PMID- 26874912 TI - Effects of glucose ingestion on circulating inflammatory mediators: Influence of sex and weight excess. AB - BACKGROUND & AIMS: Low-grade chronic inflammation is involved in the pathophysiology of obesity. However, little is known about the influence of sex and sex hormones on surrogate inflammatory markers and mediators, particularly after glucose ingestion. DESIGN: Observational study. METHODS: We measured the circulating concentrations of interleukin-6, interleukin-18, macrophage migration inhibitory factor, matrix metallopeptidase-9, monocyte chemotactic protein-1 and pentraxin-3, in the fasting state and during a 75 g oral glucose tolerance test, in 24 women and 25 men. Eleven men and 11 women were lean whereas 14 men and 13 women had weight excess. RESULTS: Anti-inflammatory cytokines (interleukin-6 and interleukin-18) were increased in the fasting state and/or decreased in some women during the oral glucose tolerance test, as opposed to inflammatory mediators such as macrophage migration inhibitory factor and matrix metallopeptidase-9 that increased during the oral glucose tolerance test especially in subjects with weight excess. Body mass index and waist circumference were the main determinants of these changes. Fasting pentraxin-3 levels were especially increased in lean women in parallel to a decrease in free testosterone levels, and decreased during the oral glucose tolerance test as opposed to the increase in insulin concentrations. CONCLUSIONS: The circulating concentrations of markers of low-grade chronic inflammation in young healthy adults are not only influenced by obesity but also by abdominal adiposity, fasting and glucose ingestion and, in some cases, by sex and sex hormones. These influences should be considered when these markers are used as surrogate markers of the inflammatory milieu associated with obesity. PMID- 26874914 TI - Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) and the role of next-generation sequencing. AB - Refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) shares overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). RARS-T is characterized by SF3B1 and JAK2 mutations and prognosis is considered to be better than MDS but not as good as MPN. The objective of the study was to identify predictors of survival in RARS-T. We analyzed clinical and laboratory variables in 82 patients and applied a 27-gene NGS assay to 48 marrow samples obtained at diagnosis. 94% of patients had >=1 mutations; common mutations being: SF3B1 85%, JAK2V617F 33%, ASXL1 29%, DNMT3A 13%, SETBP1 13% and TET2 10%. In a multivariable survival analysis (n = 82), anemia (P = 0.02) [HB< 10 gm/dl: HR 2.3, 95% CI 1.2-4.6] and abnormal karyotype (P =.01) [HR 6.1, 95% CI 2.7-13.8] were independently prognostic for inferior survival. In patients with NGS information (n = 48), univariate analysis showed association between poor survival and presence of SETBP1 (P = 0.04) or ASXL1 (P = 0.08) mutations whereas the absence of these mutations (ASXL1wt/SETBP1wt) was favorable (P = 0.04); the number of concurrent mutations did not provide additional prognostication (P = 0.3). We developed a HR-weighted prognostic model, with 2 points for an abnormal karyotype, 1 point for either ASXL1 and/or SETBP1 mutations, and 1 point for a HB level < 10 gm/dl, which effectively stratified patients into three risk categories; low (0 points), intermediate (1 point) and high (>=2 points), with median survivals of 80, 42 and 11 months respectively (P = 0.01). In summary, we confirm the unique mutational landscape in RARS-T and provide a novel mutation-enhanced prognostic model. PMID- 26874915 TI - The profile of psychiatric symptoms exacerbated by methamphetamine use. AB - BACKGROUND: Methamphetamine use can produce symptoms almost indistinguishable from schizophrenia. Distinguishing between the two conditions has been hampered by the lack of a validated symptom profile for methamphetamine-induced psychiatric symptoms. We use data from a longitudinal cohort study to examine the profile of psychiatric symptoms that are acutely exacerbated by methamphetamine use. METHODS: 164 methamphetamine users, who did not meet DSM-IV criteria for a lifetime primary psychotic disorder, were followed monthly for one year to assess the relationship between days of methamphetamine use and symptom severity on the 24-item Brief Psychiatric Rating Scale. Exacerbation of psychiatric symptoms with methamphetamine use was quantified using random coefficient models. The dimensions of symptom exacerbation were examined using principal axis factoring and a latent profile analysis. RESULTS: Symptoms exacerbated by methamphetamine loaded on three factors: positive psychotic symptoms (suspiciousness, unusual thought content, hallucinations, bizarre behavior); affective symptoms (depression, suicidality, guilt, hostility, somatic concern, self-neglect); and psychomotor symptoms (tension, excitement, distractibility, motor hyperactivity). Methamphetamine use did not significantly increase negative symptoms. Vulnerability to positive psychotic and affective symptom exacerbation was shared by 28% of participants, and this vulnerability aligned with a past year DSM-IV diagnosis of substance-induced psychosis (38% vs. 22%, chi(2)(df1)=3.66, p=0.056). CONCLUSION: Methamphetamine use produced a symptom profile comprised of positive psychotic and affective symptoms, which aligned with a diagnosis of substance-induced psychosis, with no evidence of a negative syndrome. PMID- 26874917 TI - MY APPROACH to the practical management of anticoagulation in patients with atrial fibrillation. PMID- 26874916 TI - Neural correlates of cigarette health warning avoidance among smokers. AB - BACKGROUND: Eye-tracking technology has indicated that daily smokers actively avoid pictorial cigarette package health warnings. Avoidance may be due to a pre cognitive perceptual bias or a higher order cognitive bias, such as reduced emotional processing. Using electroencephalography (EEG), this study aimed to identify the temporal point at which smokers' responses to health warnings begin to differ. METHOD: Non-smokers (n=20) and daily smokers (n=20) viewed pictorial cigarette package health warnings and neutral control stimuli. These elicited Event Related Potentials reflecting early perceptual processing (visual P1), pre attentive change detection (visual Mismatch Negativity), selective attentional orientation (P3) and a measure of emotional processing, the Late Positive Potential (LPP). RESULTS: There was no evidence for a difference in P1 responses between smokers and non-smokers. There was no difference in vMMN and P3 amplitude but some evidence for a delay in vMMN latency amongst smokers. There was strong evidence for delayed and reduced LPP to health warning stimuli amongst smokers compared to non-smokers. CONCLUSION: We find no evidence for an early perceptual bias in smokers' visual perception of health warnings but strong evidence that smokers are less sensitive to the emotional content of cigarette health warnings. Future health warning development should focus on increasing the emotional salience of pictorial health warning content amongst smokers. PMID- 26874918 TI - Detection of an early adult T-cell leukemia-lymphoma clone in lymph nodes with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma involvement. AB - A 58-year-old man was admitted to our hospital with systemic lymphadenopathy and was diagnosed with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL) by lymph node biopsy. Although he was a human T-cell leukemia virus type I (HTLV-1) carrier, Southern blot analysis of the lymph node did not show monoclonal integration of HTLV-1 provirus deoxyribonucleic acid (DNA). He achieved complete remission after chemotherapy and subsequently, autologous peripheral blood stem cell transplantation (auto-PBSCT) was performed. Fifteen months after the auto-PBSCT, abnormal lymphocytes in the peripheral blood gradually increased. Southern blot analysis revealed monoclonal integration of HTLV-1 provirus DNA and monoclonal rearrangement of TRB. He was diagnosed with chronic type adult T-cell leukemia-lymphoma (ATL), which immediately progressed to the acute type. He died of tumor progression despite intensive chemotherapy. We analyzed genomic alterations of the ALCL and ATL cells using array comparative genomic hybridization. We found that the genomic alteration pattern differed between the two diseases. T-cell receptor clonality analysis using polymerase chain reaction (PCR) showed that the T-cell clone of the ATL was present in the lymph nodes with ALCL involvement, but not in peripheral blood. This finding suggests that lymph nodes can serve as a niche for ATL development. PMID- 26874920 TI - A PROM primer. PMID- 26874921 TI - Fat grafting & the philosopher's stone. PMID- 26874919 TI - Parietal hyper-connectivity, aberrant brain organization, and circuit-based biomarkers in children with mathematical disabilities. AB - Mathematical disabilities (MD) have a negative life-long impact on professional success, employment, and health outcomes. Yet little is known about the intrinsic functional brain organization that contributes to poor math skills in affected children. It is now increasingly recognized that math cognition requires coordinated interaction within a large-scale fronto-parietal network anchored in the intraparietal sulcus (IPS). Here we characterize intrinsic functional connectivity within this IPS-network in children with MD, relative to a group of typically developing (TD) children who were matched on age, gender, IQ, working memory, and reading abilities. Compared to TD children, children with MD showed hyper-connectivity of the IPS with a bilateral fronto-parietal network. Importantly, aberrant IPS connectivity patterns accurately discriminated children with MD and TD children, highlighting the possibility for using IPS connectivity as a brain-based biomarker of MD. To further investigate regional abnormalities contributing to network-level deficits in children with MD, we performed whole brain analyses of intrinsic low-frequency fluctuations. Notably, children with MD showed higher low-frequency fluctuations in multiple fronto-parietal areas that overlapped with brain regions that exhibited hyper-connectivity with the IPS. Taken together, our findings suggest that MD in children is characterized by robust network-level aberrations, and is not an isolated dysfunction of the IPS. We hypothesize that intrinsic hyper-connectivity and enhanced low-frequency fluctuations may limit flexible resource allocation, and contribute to aberrant recruitment of task-related brain regions during numerical problem solving in children with MD. PMID- 26874922 TI - Mitochondrial Dysfunction Meets Senescence. AB - Cellular senescence and mitochondrial dysfunction are hallmarks of ageing, but until now their relationship has not been clear. Recent work by Wiley et al. shows that mitochondrial defects can cause a distinct senescence phenotype termed MiDAS (mitochondrial dysfunction-associated senescence). MiDAS has a specific secretome that is able to drive some of the aging phenotypes. These findings suggest novel therapeutic opportunities for treating age-related pathologies. PMID- 26874924 TI - Cavernoplasty with oral mucosa graft for the surgical treatment of Peyronie's disease. AB - BACKGROUND: Peyronie's disease is a disorder of the tunica albuginea and causes penile curvature, requiring surgical correction when the deformity impedes penetration. MATERIAL AND METHODS: Retrospective analysis of the short-term results (penile length, angle of curvature and erectile function) of treating Peyronie's disease in 10 patients through cavernoplasty with oral mucosa graft. Essentially, the treatment included the incision of the fibrotic plaque with electrical scalpel and the subsequent coating of the cavernous defect using a patch of oral mucosa. At month 6, we measured the penile length and curvature and recorded the erectile function using the International Index of Erectile Function 5 (IIEF-5) questionnaire. Finally, the patients were asked "Would you undergo the same operation again?". RESULTS: The mean age was 53.4 years. The average and median follow-up was 22.7 months and 24 months, respectively. The mean preoperative curvature was 68.5 degrees (50 degrees -90 degrees ), the mean penile length was 11.2cm (9-15) and the mean IIEF-5 score was 16.1 (8-25). The mean postoperative penile length was 10.7cm, and the mean IIEF-5 score was 18.9. The differences between the preoperative and postoperative values were not statistically significant (P=ns). One patient developed erectile dysfunction. In all cases, the residual curvature was <20 degrees . Nine patients (90%) stated that they would undergo the same operation. CONCLUSIONS: The short-term results suggest that cavernoplasty with oral mucosa graft can be an alternative to traditional grafts for surgically correcting Peyronie's disease. PMID- 26874925 TI - Alignment of oral health-related with health-related quality of life assessment. PMID- 26874923 TI - Heat Shock Proteins Promote Cancer: It's a Protection Racket. AB - Heat shock proteins (HSP) are expressed at high levels in cancer and form a fostering environment that is essential for tumor development. Here, we review the recent data in this area, concentrating mainly on Hsp27, Hsp70, and Hsp90. The overriding role of HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer genes. Thus, elevated HSPs are required for many of the traits that underlie the morbidity of cancer, including increased growth, survival, and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor-mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment. PMID- 26874926 TI - Medication-related osteonecrosis of the jaw; what should we do as prosthodontists? PMID- 26874927 TI - Effectiveness of a pay-for-performance intervention to improve maternal and child health services in Afghanistan: a cluster-randomized trial. AB - BACKGROUND: A cluster randomized trial of a pay-for-performance (P4P) scheme was implemented in Afghanistan to test whether P4P could improve maternal and child (MCH) services. METHODS: All 442 primary care facilities in 11 provinces were matched by type of facility and outpatient volume, and randomly assigned to the P4P or comparison arm. P4P facilities were given bonus payments based on the MCH services provided. An endline household sample survey was conducted in 72 randomly selected matched pair catchment areas (3421 P4P households; 3427 comparison).The quality of services was assessed in 81 randomly sampled matched pairs of facilities. Data collectors and households were blinded to the intervention assignment. MCH outcomes were assessed at the cluster level. RESULTS: There were no substantial differences in any of the five MCH coverage indicators (P4P vs comparison): modern contraception(10.7% vs 11.2% (P = 0.90); antenatal care: 56.2% vs 55.6% (P = 0.94); skilled birth attendance (33.9% vs 28.5%, P = 0.17); postnatal care (31.2% vs 30.3%, P = 0.98); and childhood pentavalent3 vaccination (49.6 vs 52.3%, P = 0.41), or in the equity measures. There were substantial increases in the quality of history and physical examinations index (P = 0.01); client counselling index (P = 0.01); and time spent with patients (P = 0.05). Health workers reported limited understanding about the bonuses. CONCLUSIONS: The intervention had minimal effect, possibly due to difficulties communicating with health workers and inattention to demand-side factors. P4P interventions need to consider management and community demand issues. PMID- 26874928 TI - Identification of neurodevelopmental trajectories in infancy and of risk factors affecting deviant development: a longitudinal birth cohort study. AB - BACKGROUND: We investigate patterns of neurodevelopmental trajectories in infants, using a representative population, and identify risk factors that predict delayed growth. METHODS: Participating infants (n = 952; 82.8% of the total sample) were assessed by Mullen Scales of Early Learning at seven time points, from 1 month to 24 months of age. Mothers were recruited in early pregnancy and data on demographic characteristics were collected during pregnancy. Trajectory patterns were investigated using latent class growth analysis, and risk factors for the derived trajectory classes were investigated by multinomial logistic regression. RESULTS: Participants were found to be a fairly representative sample with respect to their demographic characteristics. Five classes of high normal (11.5%), normal (49.2%), low normal (21.2%), delayed (14.1%), and markedly delayed (4.0%) were identified. The markedly delayed class was characterized by overall delay from the early developmental stages; notably, such delay first became salient in motor domains and was then exceeded by language domains, especially receptive language. This class was predicted by male sex (odds ratio 4.0; 95% confidence interval 1.7-9.1), small for gestational age (2.8; 1.0-7.5), low placenta-to-birthweight ratio (2.8; 1.2-6.4) and low maternal education (4.7; 1.2-19.0). The delayed class was characterized by gradual downward deviation after the first birthday, and was predicted by male sex (2.5; 1.5-4.2), preterm birth (4.4; 1.6-12.6) and advanced paternal age (1.9; 1.0-3.5). CONCLUSIONS: Our results demonstrate that about 1 out of 5 infants exhibits delayed neurodevelopment. Infants with distinct patterns of delayed trajectories and varying risk factors are considered to have different pathophysiological mechanisms. PMID- 26874929 TI - Data Resource Profile: The Russia Longitudinal Monitoring Survey-Higher School of Economics (RLMS-HSE) Phase II: Monitoring the Economic and Health Situation in Russia, 1994-2013. PMID- 26874930 TI - Montelukast-induced metamorphopsia in a pediatric patient: A case report and a pharmacovigilance database analysis. PMID- 26874931 TI - Pharmacogenomic or -epigenomic biomarkers in drug treatment: Two sides of the same medal? AB - Interindividual differences in expression of ADME genes are controlled by both genetic and epigenetic factors. Much emphasis has been made to describe the genetic influence, whereas the epigenetic part is not fully understood. Currently, we utilize mainly genetic biomarkers for optimization of drug therapy, although many rare genetic variants are not taken into consideration. Now, also epigenomic biomarkers are at hand and together genetic and epigenetic biomarkers can indeed improve the predictability of drug treatment. PMID- 26874932 TI - Current methods of the analysis of immunosuppressive agents in clinical materials: A review. AB - More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. PMID- 26874933 TI - Analysing risk factors for urinary tract infection based on automated monitoring of hospital-acquired infection. AB - Urinary tract infections account for as much as one-third of all nosocomial infections. The aim of this study was to examine previously reported characteristics of patients with hospital-acquired urinary tract infections (HA UTI) using an automated infection monitoring system (Hospital-Acquired Infection Registry: HAIR). A matched case-control study was conducted to investigate the association of risk factors with HA-UTI. Patients with HA-UTI more frequently had indwelling urinary catheters or a disease in the genitourinary or nervous system than the controls. Automated hospital-acquired infection monitoring enables documentation of key risk factors to better evaluate infection control interventions in general or for selected groups of patients. PMID- 26874934 TI - Sequence type 72 community-associated meticillin-resistant Staphylococcus aureus emerged as a predominant clone of nasal colonization in newly admitted patients. AB - Current knowledge of community-associated (CA) meticillin-resistant Staphylococcus aureus (MRSA) carriage in hospitalized patients is incomplete. Genotypic characteristics of 637 nasal MRSA isolates from newly admitted patients in South Korea were investigated. Sequence type (ST) 72 accounted for 52.1%, 46.3%, and 52.8% of the isolates during the periods of 2007-2008, 2009-2010, and 2013-2014, respectively. Instead of classic MRSA clones responsible for healthcare-associated infections, including ST5 and ST239, MRSA with community genotype ST72 was the predominant strain in newly admitted patients regardless of age and home province of the patients. Active strategies are needed to prevent healthcare-associated infection by CA-MRSA. PMID- 26874935 TI - Acceptability of temporary suspension of visiting during norovirus outbreaks: investigating patient, visitor and public opinion. AB - BACKGROUND: Noroviruses are a leading cause of outbreaks globally and the most common cause of service disruption due to ward closures. Temporary suspension of visiting (TSV) is increasingly a recommended public health measure to reduce exposure, transmission and impact during norovirus outbreaks; however, preventing patient-visitor contact may contravene the ethos of person-centred care, and public acceptability of this measure is not known. AIM: To investigate the acceptability of TSV during norovirus outbreaks from the perspectives of patients, visitors and the wider public. METHODS: Cross-sectional survey of patients (N = 153), visitors (N = 175) and the public (N = 224) in three diverse areas in Scotland. Health Belief Model constructs were applied to understand ratings of acceptability of TSV during norovirus outbreaks, and to determine associations between these levels and various predictor variables. FINDINGS: The majority (84.6%) of respondents indicated that the possible benefits of TSV are greater than the possible disadvantages. Conversely, the majority (70%) of respondents disagreed that TSV 'is wrong as it ignores people's rights to have contact with family and friends'. The majority (81.6%) of respondents agreed that TSV would be more acceptable if exceptions were made for seriously ill or dying patients. Correlational analysis demonstrated that overall acceptability was positively related to perceived severity (r = 0.65), identified benefits (r = 0.54) and implementing additional communication strategies (r = 0.60); acceptability was negatively related to potential barriers (r = -0.49). CONCLUSIONS: There is greater service user and public support for the use of TSV than concerns around impinging upon patients' rights to have visitors. TSV should be considered as an acceptable infection control measure that could be implemented consistently during norovirus outbreaks. PMID- 26874936 TI - The wide spectrum of cerebrotendinous xanthomatosis: Case report of a rare but treatable disease. AB - Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive disorder of lipid storage caused by mutations in the CYP27A1 gene, coding for a sterol 27 hydroxylase, leading to increased deposition of cholesterol in multiple tissues. CTX is characterized by the association of early non-neurological manifestations and adult-onset neurological dysfunctions (spastic ataxia, dementia, psychiatric disorders, peripheral neuropathy). Early and long-term treatment with chenodeoxycholic acid (CDCA) can slow down neurological symptoms progression, but diagnosis usually has a delay of several years. We report two Italian siblings having quite different phenotypes associated to a G-to-A transition in the c-1263 terminal causing a splicing alteration. This mutation has not been described before in Italy, and has been reported once in Japan. This case widens the clinical and genetic spectrum of Cerebrotendinous Xantomatosis in Italy and would like to suggest the importance of genetic testing in patients with autosomal recessive spastic paraparesis associated with typical non-neurological symptoms. PMID- 26874937 TI - The value of dynamic radiographic myelography in addition to magnetic resonance imaging in detection lumbar spinal canal stenosis: A prospective study. AB - OBJECTIVE: MRI is regarded as the study of choice in the diagnosis of lumbar spinal stenosis. In some cases, the supine MRI leads to a misdiagnosis in the extent of lumbar spinal stenosis. Dynamic myelography can detect lumbar spinal stenosis in these cases of where the MRI may not be as sensitive. To compare the sensitivities of dynamic radiographic myelography and supine MRI in lumbar canal stenosis (LCS) patients and to determine whether dynamic radiographic myelography is a valuable diagnostic exam in the work-up of lumbar canal stenosis. PATIENTS & METHODS: Over two years, the imaging data of 100 consecutive patients who were suspected of having LCS were prospectively analyzed. All lumbar intervertebral segments were evaluated in each patient on sagittal MR T2-weighted images and lateral plane images by myelography using a semi-quantitative scoring system. The differences in scores for 5 motion segments under 3 conditions (supine MRI, upright sitting myelography and standing myelography with extension) were analyzed statistically. RESULTS: Of 100 patients with 500 analyzed intervertebral segments, 23 patients with inconclusive supine MRI results had LCS in standing myelography with extension. Compared with upright sitting myelography and supine MRI, standing myelography with extension yielded the highest score for every segment from L1/2 to L5/S1. Compared with the upright sitting myelography position, 61 more patients received a diagnosis of lumbar stenosis in the standing myelography with extension position, and 121 more stenotic segments were diagnosed. Compared with the supine MRI position, standing myelography with extension detected 64 more stenotic patients and 137 more stenotic segments. CONCLUSIO: n Based on a large patient sample, dynamic myelography is a valuable diagnostic tool in detecting lumbar spinal stenosis. Patients with lumbar spinal stenosis may have inconclusive supine MRI in 23% of cases being misdiagnosed as normal. This missed rate of LCS patients with unclear supine MRI results can be avoided with dynamic myelography. The combination of supine MRI and dynamic myelography is critical in the evaluation of LCS, especially if multisegmental findings are detected. PMID- 26874938 TI - An Australian survey of women's use of pregnancy and parenting apps. AB - BACKGROUND: There are now many pregnancy and parenting apps available on the market for both pregnancy and parenting. AIMS: To investigate how Australian women use pregnancy and parenting apps, their attitudes about the information provided and data privacy and security related to such use, and what features they look for in these apps. METHODS: An online survey was completed by 410 women who were pregnant or had given birth to at least one child in the past three years, were aged between 18 and 45 and were competent in English. FINDINGS: The use of pregnancy and parenting apps was common among the respondents. Almost three quarters of respondents had used at least one pregnancy app; half reported using at least one parenting app. Respondents found the apps useful or helpful, particularly for providing information, monitoring foetal or child development and changes in their own bodies and providing reassurance. Yet many users were not actively assessing the validity of the content of these apps or considering issues concerning the security and privacy of the personal information about themselves and their children that these apps collect. CONCLUSION: Apps are becoming important as a source of information and self-monitoring and for providing reassurance for Australian pregnant women and mothers with young children. Midwives and other healthcare professionals providing care and support for pregnant women and women in the early years of motherhood need to take women's app use into account and recognise both the potential and limitations of these apps. PMID- 26874939 TI - Getting lost: Topographic skills in acquired and developmental prosopagnosia. AB - Previous studies report that acquired prosopagnosia is frequently associated with topographic disorientation. Whether this is associated with a specific anatomic subtype of prosopagnosia, how frequently it is seen with the developmental variant, and what specific topographic function is impaired to account for this problem are not known. We studied ten subjects with acquired prosopagnosia from either occipitotemporal or anterior temporal (AT) lesions and seven with developmental prosopagnosia. Subjects were given a battery of topographic tests, including house and scene recognition, the road map test, a test of cognitive map formation, and a standardized self-report questionnaire. House and/or scene recognition were frequently impaired after either occipitotemporal or AT lesions in acquired prosopagnosia. Subjects with occipitotemporal lesions were also impaired in cognitive map formation: an overlap analysis identified right fusiform and parahippocampal gyri as a likely correlate. Only one subject with acquired prosopagnosia had mild difficulty with directional orientation on the road map test. Only one subject with developmental prosopagnosia had difficulty with cognitive map formation, and none were impaired on the other tests. Scores for house and scene recognition correlated most strongly with the results of the questionnaire. We conclude that topographic disorientation in acquired prosopagnosia reflects impaired place recognition, with a contribution from poor cognitive map formation when there is occipitotemporal damage. Topographic impairments are less frequent in developmental prosopagnosia. PMID- 26874941 TI - Social coercion of larval development in an ant species. AB - Ants provide one of the best examples of the division of labor in animal societies. While the queens reproduce, workers generally refrain from laying eggs and dedicate themselves exclusively to domestic tasks. In many species, the small diploid larvae are bipotent and can develop either into workers or queens depending mostly on environmental cues. This generates a conflicting situation between the adults that tend to rear a majority of larvae into workers and the larvae whose individual interest may be to develop into reproductive queens. We tested the social regulation of larval caste fate in the fission-performing ant Aphaenogaster senilis. We first observed interactions between resident workers and queen- and worker-destined larvae in presence/absence of the queen. The results show that workers tend to specifically eliminate queen-destined larvae when the queen is present but not when she is absent or imprisoned in a small cage allowing for volatile pheromone exchanges. In addition, we found that the presence of already developed queen-destined larvae does not inhibit the development of younger still bipotent larvae into queens. Finally, we analyzed the cuticular hydrocarbon profiles of queen- and worker-destined larvae and found no significant quantitative or qualitative difference. Interestingly, the total amount of hydrocarbons on both larval castes is extremely low, which lends credence on the chemical insignificance hypothesis of larval ants. Overall, our results suggest that workers control larval development and police larvae that would develop into queens instead of workers. Such policing behavior is similar in many aspects to what is known of worker policing among adults. PMID- 26874940 TI - Human ventromedial prefrontal lesions alter incentivisation by reward. AB - Although medial frontal brain regions are implicated in valuation of rewards, evidence from focal lesions to these areas is scant, with many conflicting results regarding motivation and affect, and no human studies specifically examining incentivisation by reward. Here, 19 patients with isolated, focal damage in ventral and medial prefrontal cortex were selected from a database of 453 individuals with subarachnoid haemorrhage. Using a speeded saccadic task based on the oculomotor capture paradigm, we manipulated the maximum reward available on each trial using an auditory incentive cue. Modulation of behaviour by motivation permitted quantification of reward sensitivity. At the group level, medial frontal damage was overall associated with significantly reduced effects of reward on invigorating saccadic velocity and autonomic (pupil) responses compared to age-matched, healthy controls. Crucially, however, some individuals instead showed abnormally strong incentivisation effects for vigour. Increased sensitivity to rewards within the lesion group correlated with damage in subgenual ventromedial prefrontal cortex (vmPFC) areas, which have recently become the target for deep brain stimulation (DBS) in depression. Lesion correlations with clinical apathy suggested that the apathy associated with prefrontal damage is in fact reduced by damage at those coordinates. Reduced reward sensitivity showed a trend to correlate with damage near nucleus accumbens. Lesions did not, on the other hand, influence reward sensitivity of cognitive control, as measured by distractibility. Thus, although medial frontal lesions may generally reduce reward sensitivity, damage to key subregions paradoxically protect from this effect. PMID- 26874942 TI - Killer-cell immunoglobulin-like receptor genes and ligands and their role in hematologic malignancies. AB - Natural killer (NK) cells are considered crucial for the elimination of emerging tumor cells. Effector NK-cell functions are controlled by interactions of inhibitory and activating killer-cell immunoglobulin-like receptors (KIRs) on NK cells with human leukocyte antigen (HLA) class I ligands on target cells. KIR and HLA are highly polymorphic genetic systems segregating independently, creating a great diversity in KIR/HLA gene profiles in different individuals. There is an increasing evidence supporting the relevance of KIR and HLA ligand gene background for the occurrence and outcome of certain cancers. However, the data are still controversial and the mechanisms of receptor-ligand mediated NK-cell action remain unclear. Here, the main characteristics and functions of KIRs and their HLA class I ligands are reviewed. In addition, we review the HLA and KIR correlations with different hematological malignancies and discuss our current understanding of the biological significance and mechanisms underlying these associations. PMID- 26874943 TI - Timeliness of Colonoscopy After Abnormal Fecal Test Results in a Safety Net Practice. AB - Fecal testing can only reduce colorectal cancer mortality if patients with an abnormal test result receive a follow-up colonoscopy. As part of the Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) project, we examined factors associated with adherence to follow-up colonoscopy among patients with abnormal fecal test results. As part of STOP CRC outreach, Virginia Garcia Memorial Health Center staff distributed 1753 fecal immunochemical tests (FIT), of which 677 (39 %) were completed, and 56 had an abnormal result (8 %). Project staff used logistic regression analyses to examine factors associated with colonoscopy referral and completion. Of the 56 patients with abnormal FIT results; 45 (80 %) had evidence of a referral for colonoscopy, 32 (57 %) had evidence of a completed colonoscopy within 18 months, and 14 (25 %) within 60 days of an abnormal fecal test result. In adjusted analysis, Hispanics had lower odds of completing follow-up colonoscopy within 60 days than non Hispanic whites (adjusted OR 0.20; 95 % CI 0.04, 0.92). Colonoscopy within 60 days trended lower for women than for men (adjusted OR 0.25; 95 % CI 0.06-1.04). Among the 24 patients lacking medical record evidence of a colonoscopy, 19 (79 %) had a documented reason, including clinician did not pursue, patient refused, and colonoscopy not indicated. No reason was found for 21 %. Improvements are needed to increase rates of follow-up colonoscopy completion, especially among female and Hispanic patients. PMID- 26874944 TI - Worksite Cancer Prevention Activities in the National Comprehensive Cancer Control Program. AB - Workplaces are one setting for cancer control planners to reach adults at risk for cancer and other chronic diseases. However, the extent to which Centers for Disease Control and Prevention-funded National Comprehensive Cancer Control Programs (NCCCP) implement interventions in the workplace setting is not well characterized. We conducted a qualitative content analysis of program action plans submitted by NCCCP grantees from 2013 to 2015 to identify and describe cancer prevention objectives and interventions in the workplace setting. Nearly half of NCCCP action reports contained at least one cancer prevention objective or intervention in the workplace setting. Common interventions included education about secondhand smoke exposure in the workplace, and the importance of obtaining colorectal cancer screening. Workplace interventions were relatively common among NCCCP action plans, and serve as one way to address low percentages of CRC screening, and reduce risk for obesity- and tobacco-related cancers. PMID- 26874946 TI - Preventive effect of oral nicorandil on contrast-induced nephropathy in patients with renal insufficiency undergoing elective cardiac catheterization. AB - This study aims to investigate the preventive effect of oral nicorandil on contrast-induced nephropathy (CIN) in patients with renal insufficiency undergoing elective cardiac catheterization. A total of 240 patients with an estimated glomerular filtration rate (eGFR) of 60 mL/min or less, who were undergoing elective cardiac catheterization, were randomly assigned to nicorandil group (n = 120, 10 mg nicorandil, three times daily from 2 days before to 3 days after procedure) or control group (n = 120, matching placebo as the same method). The primary endpoint was the incidence of CIN defined as 25 % increase in serum creatinine (SCr) from baseline or 44 MUmol/L (0.5 mg/dL) increase in absolute value within 72 h after exposure to contrast medium. The secondary endpoints were: (1) the changes of SCr, Cystatin-C (Cys-C) and eGFR within 72 h; (2) major adverse events (MACE) occurring within 30 days. Baseline characteristics of the patients in the two groups were similar. The incidence of CIN was significantly lower in nicorandil group compared with control group (6.67 vs. 17.5 %, P = 0.017). Compared with the control group, nicorandil group tended to have a lower SCr and Cys-C levels as well as a higher eGFR at 48 h after the procedure (all P < 0.05). There was no difference about the incidence of MACE within 30 days between nicorandil group and control group (4.16 vs. 5.83 %, P = 0.767). Multivariate logistic analysis showed that nicorandil was an independent protective factor against CIN (OR = 0.260, 95 % CI = 0.1-0.676, P = 0.006). Therefore, we concluded that oral nicorandil was associated with a decline in the incidence of CIN in patients with renal insufficiency undergoing elective cardiac catheterization. PMID- 26874949 TI - DFT investigation on the decarboxylation mechanism of ortho hydroxy benzoic acids with acid catalysis. AB - A density functional theory (DFT) study was performed to explore the mechanisms of the acid-catalyzed decarboxylation reaction of salicylic acids using the B3LYP method with 6-31++G(d,p) basis set in both gas phase and aqueous environment. The alpha-protonated cation of carboxylate acid was formed during the decarboxylation process in acidic conditions, and the presence of hydrogen ions promotes decarboxylation greatly by significantly decreasing the overall reaction energy barriers to 20.98 kcal mol(-1) in gas phase and 20.93 kcal mol(-1) in water, respectively. The hydrogen in the alpha-carbon came directly from the acid rather than from the carboxyl group in neutral state. Compared with the reaction in gas phase, water in aqueous state causes the reaction to occur more easily. Substituents of methyl group, chlorine and fluorine at the ortho-position to the carboxyl of salicylic acid could further lower the decarboxylation energy barriers and facilitate the reaction. PMID- 26874948 TI - Estimation of melting points of large set of persistent organic pollutants utilizing QSPR approach. AB - The presence of polyhalogenated persistent organic pollutants (POPs), such as Cl/Br-substituted benzenes, biphenyls, diphenyl ethers, and naphthalenes has been identified in all environmental compartments. The exposure to these compounds can pose potential risk not only for ecological systems, but also for human health. Therefore, efficient tools for comprehensive environmental risk assessment for POPs are required. Among the factors vital for environmental transport and fate processes is melting point of a compound. In this study, we estimated the melting points of a large group (1419 compounds) of chloro- and bromo- derivatives of dibenzo-p-dioxins, dibenzofurans, biphenyls, naphthalenes, diphenylethers, and benzenes by utilizing quantitative structure-property relationship (QSPR) techniques. The compounds were classified by applying structure-based clustering methods followed by GA-PLS modeling. In addition, random forest method has been applied to develop more general models. Factors responsible for melting point behavior and predictive ability of each method were discussed. PMID- 26874947 TI - Gender differences in plaque characteristics of culprit lesions in patients with ST elevation myocardial infarction. AB - There is limited research on plaque characteristics of ST elevation myocardial infarction (STEMI) patients according to the gender and age. 280 Consecutive STEMI patients who underwent VH-IVUS imaging on culprit before percutaneous coronary intervention (PCI) were enrolled in this study. Women were significantly older than men (69.8 +/- 10 vs. 55.9 +/- 11.3, p < 0.001). After propensity matching, men had higher plaque burden (79.7 +/- 7.8 vs. 73.7 +/- 13.0 %, p = 0.010), more fibro-fatty tissue (12.8 +/- 9.9 vs. 9.5 +/- 6.8 %, p = 0.04) and less dense calcium than women (8.4 +/- 5.8 vs. 12.3 +/- 8.7 %, p = 0.007). Subgroups dividing by 50, 65, 75 years old, plaque burden was higher in elderly men aged 66-75 years compared to the young men aged less than 50 (75.5 +/- 9.2 vs. 68.4 +/- 10.1 %, p = 0.012). And middle aged men ranged 51-65 years showed significantly more plaque burden at minimal lumen area site than matched aged women (77.5 +/- 8.0 vs. 69.0 +/- 17.6 %, p = 0.012). Elderly women aged 66-75 years showed significantly more necrotic core (28.6 +/- 7.3 %) and dense calcium (14.9 +/- 7.5 %) compared to all the younger or matched subgroups of men. These differences in plaque composition are blunted in the very elderly of men and women aged over 75 years. The findings may explain the gender differences in clinical prognosis in STEMI patients. PMID- 26874950 TI - Age-related change in handgrip strength in men and women: is muscle quality a contributing factor? AB - Age-related changes in muscle quality and muscle mass in the forearm, which relate to decline in handgrip strength (HGS), have not been reported. The purpose of this study was to investigate the relationships between age-related declines in HGS and loss of muscle thickness and/or muscle quality in the forearm of 613 adults (306 men and 307 women) aged 20-89. Anterior forearm muscle thickness (MT ulna) and HGS were measured using an ultrasound and a hand dynamometer, respectively, in the dominant hand. Muscle quality (fMQ) was defined as a ratio of HGS to MT-ulna. HGS was similar among younger (ages 20-29, 30-39, and 40-49) groups and was progressively lower with increasing age in both sexes. MT-ulna was similar between ages 20-29 and 60-69 in men and between ages 20-29 and 70-79 in women. In men, MT-ulna was lower in ages 70-79 and 80-89 compared with other age groups. In women, MT-ulna was lower in ages 80-89 compared with ages 20-29 and 40 49. In both men and women, fMQ was identical among younger (ages 20-29, 30-39, and 40-49) groups. After that fMQ was progressively lower with age in both men and women. The results indicated that age-related decline in HGS is associated with fMQ, but it appears to be accelerated after the seventh decade due to muscle loss. PMID- 26874951 TI - Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer. AB - BACKGROUND: We previously demonstrated the potential of circulating tumor DNA (ctDNA) for the amplification of detecting HER2 in patients with gastric cancer (GC). In the present study, we focused on the clinical courses of patients who developed recurrence with GC, and investigated the potential clinical utility of the ddPCR-based HER2 copy number (CN) as a marker for the temporal and/or spatial heterogeneities of GC during treatment progress. METHOD: We enrolled 30 healthy volunteers and 60 patients with GC who underwent surgery, including 17 patients who developed recurrence. Using ribonuclease P RNA component H1 (RPPH1) as a reference gene, plasma HER2 to RPPH1 ratios (the HER2 ratio) were determined using ddPCR. RESULTS: The preoperative plasma HER2 ratio correlated with the tumor HER2 status (p < 0.001), and sensitivity and specificity were 0.733 and 0.933, respectively. Analyses of plasma samples during the postoperative follow up periods revealed that high plasma HER2 ratios were detected at the time of recurrence in 7 of 13 cases, which were diagnosed as being HER2 negative at the time of surgery. These results were supported by continuously increasing HER2 ratios thereafter with the progression of recurrent cancer. CONCLUSION: The plasma HER2 ratio determined by ddPCR is a repeatable and noninvasive approach for real-time evaluations of the HER2 status to monitor the effects of treatments for patients with HER2-positive GC and enable treatment options for patients with HER2-negative GC but positive conversion of the HER2 status after recurrence. PMID- 26874954 TI - Infestation of Raoiella indica Hirst (Trombidiformes: Tenuipalpidae) on Host Plants of High Socio-Economic Importance for Tropical America. AB - The mite Raoiella indica Hirst was recently introduced into America, where it has shown amazing ability to disseminate and broaden its range of hosts. An experiment was conducted in Cancun, Mexico, to determine infestation levels of this mite on plants recorded as hosts: coconut palm (Cocos nucifera) of cultivars Pacific Tall and Malayan Dwarf, oil palm (Elaeis guineensis) hybrids Deli x Ghana and Deli x Nigeria, Dwarf Giant banana (Musa acuminata, AAA subgroup Cavendish), Horn plantain (M. acuminata x Musa balbisiana, AAB subgroup Plantain), lobster claw (Heliconia bihai), and red ginger (Alpinia purpurata). Nursery plants of these host species or cultivars were artificially infested with R. indica in February 2011. In the four replications of 10 plants, each plant was infested with 200 R. indica specimens, and the numbers of infesting mites were recorded for 6 months. A maximum of 18,000 specimens per plant were observed on coconut Pacific Tall and Malayan Dwarf, followed by lobster claw, with a maximum of 1000 specimens per plant. Infestations were minimal for the remaining plants. Mite numbers on all plants declined naturally during the rainy season. All plant materials sustained overlapping mite generations, indicating that they are true hosts. Complementarily, infestation level was determined in backyard bananas and plantains. Correlations of infestation with plant height, distance from coconuts, and exposure to direct sunlight were estimated. Both bananas and plantains were infested by R. indica even when situated far from infested coconut palms. A Spearman correlation was found between infestation and plant height, although it was significant only for Silk plantain. PMID- 26874952 TI - Effect of depression and neuropathic pain using questionnaires on quality of life in patients with low back pain; cross-sectional retrospective study. AB - PURPOSE: The present study investigated the percentage of low back pain (LBP) patients who have depressive symptoms and neuropathic pain and analyzed the effects of these on the quality of life (QOL) in these patients. METHODS: Of the 650 new patients with LBP that visited the hospital between June 2012 and December 2013, 309 patients who completed questionnaires to assess LBP and QOL were included in the study. The questionnaire included demographic items, the self-rated depression scale (SDS)-Zung, the Japanese version of the PainDETECT questionnaire (PDQ-J), numerical pain rating scale (NRS), and QOL assessments. The patients were divided into two groups according to their SDS-Zung scores: a nondepressed group with SDS scores <40 and a depressed group with SDS-Zung scores >=50. RESULTS: One hundred twenty-five patients (40.5 %) were classified as nondepressed and 63 (20.4 %) as depressed. The mean PDQ-J score was higher in depressed patients than in nondepressed patients. The frequency of neuropathic pain was greater in depressed patients, with neuropathic pain observed in 17 of the 63 (27 %) depressed LBP patients and 11 of the 125 (9 %) nondepressed LBP patients. The SDS-Zung and PDQ-J scores of LBP patients were correlated significantly (r = 0.261, p < 0.001). Depressed patients had higher pain NRS scores and lower QOL scores compared with nondepressed patients. CONCLUSIONS: Both the depressed patients and those with neuropathic LBP had a higher level of pain, greater pain-related disability, and poorer QOL compared with nondepressed patients. This is the first study to use the SDS-Zung and PDQ-J screening questionnaires to estimate the presence of neuropathic pain associated with depressive symptoms in LBP patients and to evaluate the impact of these on QOL. PMID- 26874955 TI - Cardiovascular Disease Mortality of Medicaid Clients with Severe Mental Illness and a Co-occurring Substance Use Disorder. AB - Increasing attention focuses on cardiovascular disease (CVD) among persons with SMI. We examined, among persons with SMI, whether co-occurring substance use disorder (SUD) elevates the risk of CVD death. We linked 2002-2007 Medicaid claims data on 121,817 persons with SMI to cause and date of death information. We applied a proportional hazards model that controls for co-morbidity at baseline, atypical antipsychotic prescription medications, age, gender and race/ethnicity. Results among persons with co-occurring SUD indicate a 24 % increased risk of CVD death (hazard ratio 1.24; 95 % confidence interval 1.17 1.33). We encourage further coordination of services for this population. PMID- 26874953 TI - The nerve root sedimentation sign for differential diagnosis of lumbar spinal stenosis: a retrospective, consecutive cohort study. AB - PURPOSE: Using MR imaging, nerve root sedimentation sign (SedSign) was demonstrated to have a high sensitivity and specificity for diagnosis of symptomatic lumbar spinal stenosis (LSS) in selected patients. This study was to evaluate the diagnostic value of SedSign in differential diagnosis of LSS and non specific low back pain (LBP) in consecutive patients. METHODS: A series of consecutive patients with lumbar spinal MRI examination for back/leg pain in orthopeadic clinic were included. These patients were followed up and divided into two groups, symptomatic LSS and non-specific LBP, according to symptoms and radiological findings. Using MR images, SedSign was assessed by two spine surgeons and one radiologist independently. Then sensitivity and specificity of SedSign was calculated. RESULT: A total of 320 patients (105 LSS and 215 non specific LBP) were included. The SedSign had a sensitivity of 77.1 % and specificity of 47.0 % in the whole cohort. When these patients were stratified by dural sac cross-sectional areas (CSA), the SedSign had a sensitivity of 95.0 % and specificity of 4.7 % in patients with CSA <= 80 mm2 (severe radiologic stenosis), sensitivity of 74.2 % and specificity of 22.6 % in patients with CSA 80-100 mm2 (moderate radiologic stenosis), and sensitivity of 58.8 % and specificity of 61.0 % in patients with CSA 100-120 mm2 (mild radiologic stenosis). In selected cases composed by LSS patients with CSA <= 80 mm2 and non specific LBP patients with CSA > 120 mm2, however, the SedSign had a sensitivity of 95.0 % and specificity of 80.0 %. CONCLUSION: The present data demonstrated that the SedSign was not able to discriminate symptomatic LSS from non-specific LBP after adjusting by dural sac CSA. The diagnostic value of the SedSign was still uncertain. PMID- 26874956 TI - Relevant Cytokines in the Management of Community-Acquired Pneumonia. AB - Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed. PMID- 26874957 TI - Biological trait analysis and stability of lambda-cyhalothrin resistance in the house fly, Musca domestica L. (Diptera: Muscidae). AB - House flies, Musca domestica L., (Diptera: Muscidae), are pests of poultry and have the ability to develop resistance to insecticides. To design a strategy for resistance management, life history traits based on laboratory observations were established for lambda-cyhalothrin-resistant, susceptible and reciprocal crosses of M. domestica strains. Bioassay results showed that the lambda-cyhalothrin selected strain developed a resistance ratio of 98.34 compared to its susceptible strain. The lambda-cyhalothrin-selected strain had a relative fitness of 0.26 and lower fecundity, hatchability, lower number of next generation larvae, and net reproductive rate compared with its susceptible strain. Mean population growth rates, such as intrinsic rate of population increase, and biotic potential were lower for the lambda-cyhalothrin-selected strain compared to its susceptible strain. Resistance to lambda-cyhalothrin, indoxacarb, and abamectin was unstable while resistance to bifenthrin and methomyl was stable in the lambda-cyhalothrin selected strain of M. domestica. Development of resistance can cost considerable fitness for the lambda-cyhalothrin-selected strain. The present study provided useful information for making potential management strategies to delay resistance development in M. domestica. PMID- 26874958 TI - European Psychiatric Association (EPA) guidance on the quality of eMental health interventions in the treatment of psychotic disorders. AB - The main aim was to develop recommendations on eMental health interventions for the treatment of psychotic disorders. A systematic literature search on eMental health interventions was performed, and 24 articles about interventions in psychotic disorders were retrieved and systematically assessed for their quality. Studies were characterized by a large heterogeneity with regard to study type, sample sizes, interventions and outcome measures. Five graded recommendations were developed dealing with the feasibility of eMental health interventions, beneficial effects of psychoeducation, preliminary results of clinical efficacy, the need of moderation in peer support eMental health groups and the need to develop quality standards. PMID- 26874959 TI - EPA guidance on improving the image of psychiatry. AB - This paper explores causes, explanations and consequences of the negative image of psychiatry and develops recommendations for improvement. It is primarily based on a WPA guidance paper on how to combat the stigmatization of psychiatry and psychiatrists and a Medline search on related publications since 2010. Furthermore, focussing on potential causes and explanations, the authors performed a selective literature search regarding additional image-related issues such as mental health literacy and diagnostic and treatment issues. Underestimation of psychiatry results from both unjustified prejudices of the general public, mass media and healthcare professionals and psychiatry's own unfavourable coping with external and internal concerns. Issues related to unjustified devaluation of psychiatry include overestimation of coercion, associative stigma, lack of public knowledge, need to simplify complex mental issues, problem of the continuum between normality and psychopathology, competition with medical and non-medical disciplines and psychopharmacological treatment. Issues related to psychiatry's own contribution to being underestimated include lack of a clear professional identity, lack of biomarkers supporting clinical diagnoses, limited consensus about best treatment options, lack of collaboration with other medical disciplines and low recruitment rates among medical students. Recommendations are proposed for creating and representing a positive self-concept with different components. The negative image of psychiatry is not only due to unfavourable communication with the media, but is basically a problem of self-conceptualization. Much can be improved. However, psychiatry will remain a profession with an exceptional position among the medical disciplines, which should be seen as its specific strength. PMID- 26874963 TI - The Xanthomonas type IV pilus. AB - Type IV pili, a special class of bacterial surface filaments, are key behavioral mediators for many important human pathogens. However, we know very little about the role of these structures in the lifestyles of plant-associated bacteria. Over the past few years, several groups studying the extensive genus of Xanthomonas spp. have gained insights into the roles of played by type IV pili in bacteria host interactions and pathogenesis, motility, biofilm formation, and interactions with bacteriophages. Protein-protein interaction studies have identified T4P regulators and these, along with structural studies, have begun to reveal some of the possible molecular mechanisms that may control the extension/retraction cycles of these dynamic filaments. PMID- 26874964 TI - Linking bacterial type I toxins with their actions. AB - Bacterial type I toxin-antitoxin systems consist of stable toxin-encoding mRNAs whose expression is counteracted by unstable RNA antitoxins. Accumulating evidence suggests that these players belong to broad regulatory networks influencing overall bacterial physiology. The majority of known transmembrane type I toxic peptides have conserved structural characteristics. However, recent studies demonstrated that their mechanisms of toxicity are diverse and complex. To better assess the current state of the art, type I toxins can be grouped into two classes according to their location and mechanisms of action: membrane associated toxins acting by pore formation and/or by nucleoid condensation; and cytosolic toxins inducing nucleic acid cleavage. This classification will evolve as a result of future investigations. PMID- 26874961 TI - Brain tumour differentiation: rapid stratified serum diagnostics via attenuated total reflection Fourier-transform infrared spectroscopy. AB - The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 MUl of human serum, attenuated total reflection-Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked. PMID- 26874965 TI - Impact and insights from ancient repetitive elements in plant genomes. AB - Transposable elements and other repeated sequences are predominant contributors to most plant genomes. The vast majority of repeated elements accumulate mutations to the extent of becoming anonymous sequences, also known as 'genomic dark matter' which is also thought to contribute significantly to the composition of plant genomes. This review aims to highlight recent methods and analyses suggesting that ancient repeats have profound effects on plant genome biology. PMID- 26874966 TI - Future-proof crops: challenges and strategies for climate resilience improvement. AB - Breeding for stress-resilient crops strongly depends on technological and biological advancements that have provided a wealth of information on genetic variants and their contribution to stress tolerance. In the context of the upcoming challenges for agriculture due to climate change, such as prolonged and/or increased stress intensities, CO2 increase and stress combinations, hierarchizing this information is key to accelerating crop improvement towards sustained or even increased productivity. We propose traits with high scalability to yield and crop performance that can be targeted for improvement and provide examples of recent discoveries with potential applicability in breeding. Critical to success is the integrated analysis of the phenotypes of genetic variants across different environmental variables using modelling approaches and high throughput phenotyping. PMID- 26874967 TI - Learning contextualized semantics from co-occurring terms via a Siamese architecture. AB - One of the biggest challenges in Multimedia information retrieval and understanding is to bridge the semantic gap by properly modeling concept semantics in context. The presence of out of vocabulary (OOV) concepts exacerbates this difficulty. To address the semantic gap issues, we formulate a problem on learning contextualized semantics from descriptive terms and propose a novel Siamese architecture to model the contextualized semantics from descriptive terms. By means of pattern aggregation and probabilistic topic models, our Siamese architecture captures contextualized semantics from the co-occurring descriptive terms via unsupervised learning, which leads to a concept embedding space of the terms in context. Furthermore, the co-occurring OOV concepts can be easily represented in the learnt concept embedding space. The main properties of the concept embedding space are demonstrated via visualization. Using various settings in semantic priming, we have carried out a thorough evaluation by comparing our approach to a number of state-of-the-art methods on six annotation corpora in different domains, i.e., MagTag5K, CAL500 and Million Song Dataset in the music domain as well as Corel5K, LabelMe and SUNDatabase in the image domain. Experimental results on semantic priming suggest that our approach outperforms those state-of-the-art methods considerably in various aspects. PMID- 26874968 TI - Projective synchronization of nonidentical fractional-order neural networks based on sliding mode controller. AB - This paper investigates global projective synchronization of nonidentical fractional-order neural networks (FNNs) based on sliding mode control technique. We firstly construct a fractional-order integral sliding surface. Then, according to the sliding mode control theory, we design a sliding mode controller to guarantee the occurrence of the sliding motion. Based on fractional Lyapunov direct methods, system trajectories are driven to the proposed sliding surface and remain on it evermore, and some novel criteria are obtained to realize global projective synchronization of nonidentical FNNs. As the special cases, some sufficient conditions are given to ensure projective synchronization of identical FNNs, complete synchronization of nonidentical FNNs and anti-synchronization of nonidentical FNNs. Finally, one numerical example is given to demonstrate the effectiveness of the obtained results. PMID- 26874960 TI - EPA guidance on mental health and economic crises in Europe. AB - This European Psychiatric Association (EPA) guidance paper is a result of the Working Group on Mental Health Consequences of Economic Crises of the EPA Council of National Psychiatric Associations. Its purpose is to identify the impact on mental health in Europe of the economic downturn and the measures that may be taken to respond to it. We performed a review of the existing literature that yields 350 articles on which our conclusions and recommendations are based. Evidence-based tables and recommendations were developed through an expert consensus process. Literature dealing with the consequences of economic turmoil on the health and health behaviours of the population is heterogeneous, and the results are not completely unequivocal. However, there is a broad consensus about the deleterious consequences of economic crises on mental health, particularly on psychological well-being, depression, anxiety disorders, insomnia, alcohol abuse, and suicidal behaviour. Unemployment, indebtedness, precarious working conditions, inequalities, lack of social connectedness, and housing instability emerge as main risk factors. Men at working age could be particularly at risk, together with previous low SES or stigmatized populations. Generalized austerity measures and poor developed welfare systems trend to increase the harmful effects of economic crises on mental health. Although many articles suggest limitations of existing research and provide suggestions for future research, there is relatively little discussion of policy approaches to address the negative impact of economic crises on mental health. The few studies that addressed policy questions suggested that the development of social protection programs such as active labour programs, social support systems, protection for housing instability, and better access to mental health care, particularly at primary care level, is strongly needed. PMID- 26874970 TI - Impact responses of the cervical spine: A computational study of the effects of muscle activity, torso constraint, and pre-flexion. AB - Cervical spine injuries continue to be a costly societal problem. Future advancements in injury prevention depend on improved physical and computational models, which are predicated on a better understanding of the neck response during dynamic loading. Previous studies have shown that the tolerance of the neck is dependent on its initial position and its buckling behavior. This study uses a computational model to examine three important factors hypothesized to influence the loads experienced by vertebrae in the neck under compressive impact: muscle activation, torso constraints, and pre-flexion angle of the cervical spine. Since cadaver testing is not practical for large scale parametric analyses, these factors were studied using a previously validated computational model. On average, simulations with active muscles had 32% larger compressive forces and 25% larger shear forces-well in excess of what was expected from the muscle forces alone. In the short period of time required for neck injury, constraints on torso motion increased the average neck compression by less than 250N. The pre-flexion hypothesis was tested by examining pre-flexion angles from neutral (0 degrees ) to 64 degrees . Increases in pre-flexion resulted in the largest increases in peak loads and the expression of higher-order buckling modes. Peak force and buckling modality were both very sensitive to pre-flexion angle. These results validate the relevance of prior cadaver models for neck injury and help explain the wide variety of cervical spine fractures that can result from ostensibly similar compressive loadings. They also give insight into the mechanistic differences between burst fractures and lower cervical spine dislocations. PMID- 26874971 TI - Predictors of malignancy development in patients with chronic pruritus. AB - BACKGROUND: Patients with pruritus have been shown to have an increased incidence of certain subtypes of malignancy. OBJECTIVE: To assess predictors of malignancy in patients with chronic pruritus without prior dermatologic diagnoses. METHODS: Case-control study of 398 patients with chronic pruritus who developed a malignancy were compared with 8346 patients with chronic pruritus who did not develop a malignancy. Primary outcomes were odds of developing incident malignancy. RESULTS: Age greater than 60 years (OR 4.04, 95% CI 3.08, 5.31), male sex (OR 1.39, 95% CI 1.13, 1.71) and liver disease (OR 2.37, 95% CI 1.00, 5.65) were predictors of malignancy development in patients with chronic pruritus and non-diseased skin. In an exploratory analysis with multiple imputation via chained equations, age greater than 60 years (OR 4.13, 95% CI 3.15, 5.42), male sex (OR 1.26, 95% CI 1.02, 1.55), and current or prior smoking (OR 2.02, 95% CI 1.42, 2.88) were predictors of malignancy development in patients with chronic pruritus and non-diseased skin. LIMITATIONS: Potential for misclassification and detection biases. Missing data. CONCLUSIONS AND RELEVANCE: In patients with chronic pruritus without concomitant dermatologic diagnoses, older age, male sex, liver disease and tobacco abuse increase the odds of an underlying malignancy. PMID- 26874969 TI - Human cartilage endplate permeability varies with degeneration and intervertebral disc site. AB - Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50 60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1-0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics. PMID- 26874972 TI - De-coding and re-coding RNA recognition by PUF and PPR repeat proteins. AB - PUF and PPR proteins are two families of alpha-helical repeat proteins that recognize single-stranded RNA sequences. Both protein families hold promise as scaffolds for designed RNA-binding domains. A modular protein RNA recognition code was apparent from the first crystal structures of a PUF protein in complex with RNA, and recent studies continue to advance our understanding of natural PUF protein recognition (de-coding) and our ability to engineer specificity (re coding). Degenerate recognition motifs make de-coding specificity of individual PPR proteins challenging. Nevertheless, re-coding PPR protein specificity using a consensus recognition code has been successful. PMID- 26874973 TI - Role of Inter-Observer Variability and Quantification of Muscularis Propria in the Pathological Staging of Bladder Cancer. AB - INTRODUCTION: Pathological staging of bladder cancer (BC) on trans-urethral bladder resection (TURB) specimens is critical for the indication of radical cystectomy (RC). MATERIALS AND METHODS: We aimed to assess the inter-observer variability among dedicated and not dedicated genito-urinary pathologists (GUP) and the predictive value of the amount of muscularis propria (MP) in the TURB specimens to predict accurate staging in RC. We selected 101 patients with at least 1 diagnosis of pT1 high grade BC who underwent RC during the history of disease. All the pathological TURB and RC specimens were reviewed by 3 GUPs, and concordance among them and with the original pathology report (OPR) was made. The presence and the extent of MP was measured in all the TURB specimens and correlated to stage at RC. RESULTS: Excellent (0.90 >= K >= 0.74) diagnostic concordance was reached among GUP while only good (0.77 >= K >= 0.67) with the OPR on stage and grade in TURBs. We found a general up-stage in the OPR compared with the GUP review. After histological review, 34.4% cases were downstaged to pT1 from pT2 and 10.1% from pT1 to pTa. The presence of MP was associated with a better discrimination of the stage at RC (P = .00065), and a trend towards correlation was found with its extent (area under the curve-receiver operator characteristic = 0.752; best cut-off 3.69 mm). CONCLUSION: The implementation of dedicated GUP can improve diagnostic sensitivity and specificity in BC diagnosis. The amount of MP and perhaps its extent in pT1 TURB speciments can predict more accurate cancer stage at RC. PMID- 26874974 TI - Correlation between overall survival and other endpoints in metastatic breast cancer with second- or third-line chemotherapy: Literature-based analysis of 24 randomized trials. AB - BACKGROUND AND OBJECTIVE: Correlations between overall survival (OS) and other endpoints have been evaluated in patients with metastatic breast cancer (MBC) who received first-line chemotherapy. However, no corresponding analysis has been accomplished for patients who have undergone second- or third-line chemotherapy. METHODS: We evaluated the potential of progression-free survival (PFS)/time to progression (TTP) and objective response rate (ORR) as surrogates of OS when OS data were not available. Correlations were evaluated by Spearman's rank correlation coefficient (rs) and weighted linear regression model. Subgroup analyses were performed for previous chemotherapy, regimen, study endpoint, study period and HER2 status. RESULTS: Twenty-four randomized trials involving 8617 patients were included for analysis. The correlation between PFS/TTP and OS was 0.7824 (95% CI: 0.6034-0.8702), whereas ORR did not strongly correlate with OS (rs=0.5398, 95%CI: 0.2942-0.7233). Further, the association between hazard ratios (HRs) of PFS/TTP and OS of the 22 randomized studies showed a moderate correlation (rs=0.5725, 95%CI: 0.1735-0.8277); the slope of the regression model (beta) was 0.5366 (95%CI: 0.3479-0.7253). In particular, the PFS/OS correlation for HER2-positive MBC patients was stronger (rs=0.9515, 95%CI: 0.7009-1.0000; beta=0.8728, 95%CI: 0.0795-1.6661). CONCLUSIONS: These results suggest that PFS/TTP is a useful early endpoint for patients with MBC who have undergone second- or third-line chemotherapy, especially for those who are HER2-positive. PMID- 26874975 TI - [Systemic therapies administration for adult patients in neuro-oncology: The standards of the Association of the neuro-oncologists of French expression (ANOCEF)]. PMID- 26874976 TI - Is high cancer rate in human due to a weakness in biology resulting from the rapid increase in lifetime expectancy? PMID- 26874977 TI - Lack of Utility of Nasopharyngeal Swabs for Diagnosis of Burkholderia pseudomallei Pneumonia in Paediatric Patients. AB - Diagnosis of Burkholderia pseudomallei pneumonia in children is challenging. We investigated the utility of nasopharyngeal swabs taken from 194 paediatric patients on admission with radiologically proven pneumonia. Melioidosis was proven in 0.5% of samples tested and only in a third of those known to be bacteraemic with B. pseudomallei. It appears unlikely that culture of nasopharyngeal secretions is helpful to confirm B. pseudomallei pneumonia in paediatric patients. PMID- 26874979 TI - Au@Cu2O stellated polytope with core-shelled nanostructure for high-performance adsorption and visible-light-driven photodegradation of cationic and anionic dyes. AB - Au nanoparticles were covered by Cu2O nanoparticles shell and then Au@Cu2O stellated polytope was synthesized by a facile aqueous solution approach. The samples were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction patterns, X-ray photoelectron spectroscopy, Brunner Emmet-Teller measurements, and Ultraviolet-visible spectroscopy analysis. With good aqueous dispersibility, surface positive charge, and high chemisorption capacity, Au@Cu2O could be used for anionic dyes removal. Compared with Degussa P25-TiO2, the adsorption of anionic dyes (acid violet 43 or methyl blue, 5.0 mg L(-1)) onto Au@Cu2O was increased by 90.12% and 50.8%, respectively. The photodegradation activity of methyl orange and methyl violet were in the declining order: Au@Cu2O>Cu2O-Au nanocomposites>Cu2O>P25-TiO2. The synergistic effect of coupling Au core with Cu2O shell on the dyes photodegradation was observed. The photoexcited electrons from Cu2O conduction band could be captured by Au nanoparticles, resulting in an improved electron-hole separation. Moreover, a Schottky barrier was assumed to form at the Cu2O-Au interface and Au NPs as electron sink could reduce the recombination of photoinduced electrons and holes, facilitating the photocatalytic interface reaction. The geometry of core-shell and stellated polytope is effective in the design of Cu2O-Au nanocomposites for adsorption and photocatalysis. PMID- 26874978 TI - Titanium dental implants surface-immobilized with gold nanoparticles as osteoinductive agents for rapid osseointegration. AB - Gold nanoparticles (GNPs) are quite attractive materials for use as osteogenic agents due to their potential effects on the stimulation of osteoblast differentiation. In this study, an osseo-integrated titanium (Ti) implant surface coated with GNPs was used for promotion of bone regeneration. We prepared a silanized Ti surface by chemical treatment of (3-Mercaptopropyl) trimethoxysilane (MPTMS) and immobilized the GNP layer (Ti-GNP) on their surfaces via Au-S bonding. The GNP layer is uniformly immobilized on the surface and the layer covers the titanium oxide surface well, as confirmed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The Ti-GNP was used to investigate the effectiveness of this system both in vitro and in vivo. The in vitro results showed that the Ti-GNP significantly enhances the osteogenic differentiation with increased mRNA expression of osteogenic differentiation specific genes in human adipose-derived stem cells (ADSCs). Furthermore, the in vivo results showed that Ti-GNP had a significant influence on the osseous interface formation. Through these in vitro and vivo tests, we found that Ti-GNP can be useful as osseo-integration inducing dental implants for formation of an osseous interface and maintenance of nascent bone formation. PMID- 26874980 TI - Drop impact on natural porous stones. AB - Drop impact and spreading on three natural porous stones are experimentally determined using high-speed imaging and compared with spreading over an impermeable steel surface. The dynamic non-wetting behavior during spreading and the hydrophobic contact angle >90 degrees is attributed to the presence of an air layer between the droplet and the porous substrate. As the contact line pins at maximum spreading on the porous stone, the maximum spreading determines the liquid contact area on such substrate. The droplet gets pinned when the air layer is broken at the contact line and capillary forces develop in fines pores at the droplet edge, pinning the droplet. Maximum spreading on porous stones increases with impact velocity but does not scale with Weber number at low impact velocity. It is demonstrated that dynamic wetting plays an important role in the spreading at low velocity and that the dynamic wetting as characterized by the dynamic contact angle thetaD has to be taken into account for predicting the maximum spreading. Correcting the maximum spreading ratio with the dynamic wetting behavior, all data for porous stones and non-porous substrate collapse onto a single curve. PMID- 26874981 TI - Dynamical behaviors of structural, constrained and free water in calcium- and magnesium-silicate-hydrate gels. AB - HYPOTHESIS: The mechanical properties of cement pastes depend strongly on their porosities. In a saturated paste, the porosity links to the free water volume after hydration. Structural water, constrained water, and free water have different dynamical behavior. Hence, it should be possible to extract information on pore system by exploiting the water dynamics. EXPERIMENTS: We investigated the slow dynamics of hydration water confined in calcium- and magnesium-silicate hydrate (C-S-H and M-S-H) gels using high-resolution quasi-elastic neutron scattering (QENS) technique. C-S-H and M-S-H are the chemical binders present in calcium rich and magnesium rich cements. We measured three M-S-H samples: pure M S-H, M-S-H with aluminum-silicate nanotubes (ASN), and M-S-H with carboxyl group functionalized ASN (ASN-COOH). A C-S-H sample with the same water content (i.e. 0.3) is also studied for comparison. FINDINGS: Structural water in the gels contributes to the elastic component of the QENS spectrum, while constrained water and free water contribute the quasi-elastic component. The quantitative analysis suggests that the three components vary for different samples and indicate the variance in the system porosity, which controls the mechanical properties of cement pastes. PMID- 26874982 TI - A synergetic analysis method for antifouling behavior investigation on PES ultrafiltration membrane with self-assembled TiO2 nanoparticles. AB - Fouling of ultrafiltration (UF) membranes is a major impediment for their use in drinking water production. Mixed matrix membranes (MMMs) may have great opportunities in dealing with this challenge due to their hierarchical structures and multiple functionalities. In this study, a synergetic analysis method based on intermolecular adhesion force measurement and fouling process simulation was applied to investigate the fouling mechanism of polyethersulfone (PES) UF membranes containing in situ self-assembled TiO2 nanoparticles (NPs). The fouling resistance behavior and antifouling mechanism of the newly developed composite membranes were investigated with sodium alginate (SA), bovine serum albumin (BSA) and humic acid (HA) as model organic foulants. An improved antifouling effect was conspicuously observed for the composite membranes, expressed by a lower flux decline and significantly better cleaning efficiency. A strong correlation between the self-assembled structure of TiO2 NPs and the antifouling behavior of the composite membrane was observed. A lower magnitude and a narrower distribution of adhesion forces for the composite membrane suggest the effective suppression of foulants adsorption on the clean or fouled membrane. The simulation analysis indicates that the main fouling mechanism was standard blocking and cake filtration, further confirming the superiority of the NPs self assembled structure in mitigating membrane fouling. This dual analysis method may provide a promising technological support for the application of modified UF membranes with self-assembled NPs in drinking water production. PMID- 26874983 TI - Percutaneous irreversible electroporation of a renal tumor: Anesthetic management. AB - Percutaneous irreversible electroporation (IRE) is a novel tumour ablation method. The application of short and high-voltage electrical pulses to the target lesion induces alterations in cell membrane permeability, finally causing tumour cell death. The extremely high-voltage that is needed in this technique requires the surveillance and management of an experienced anaesthesiologist, as it involves a significant risk of complications, such as cardiac arrhythmias or seizures. The case is presented of a 66 year-old patient diagnosed with a renal adenocarcinoma, and who received without intention-to-cure IRE under general anaesthesia. This case represents the first time this type of technique is used in Spain. PMID- 26874984 TI - Polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs in the coastal seawater, surface sediment and oyster from Dalian, Northeast China. AB - A total of 46 polycyclic aromatic hydrocarbons (PAHs, 21 parent and 25 alkylated) were determined in seawater, surface sediment and oyster from coastal area of Dalian, North China. The concentration of Sigma46PAHs in seawater, sediment, and oyster were 136-621 ng/L, 172-4700 ng/g dry weight (dw) and 60.0-129 ng/g wet weight (ww) in winter, and 65.0-1130 ng/L, 71.1-1090 ng/g dw and 72.8-216 ng/g ww in summer, respectively. High PAH levels were found in industrial area both in winter and summer. Selected PAH levels in sediments were compared with Sediments Quality Guidelines (ERM-ERL, TEL-PEL indexes) for evaluation probable toxic effects on marine organism and the results indicate that surface sediment from all sampling sites have a low to medium ecotoxicological risk. Daily intake of PAHs via oyster as seafood by humans were estimated and the results indicated that oyster intake would not pose a health risk to humans even 30 days after a oil spill accident near by. Water-sediment exchange analysis showed that, both in winter and summer, the fluxes for most high molecular weight PAHs were from seawater to sediment, while for low molecular weight PAHs, an equilibrium was reached between seawater and sediment. PMID- 26874985 TI - Antioxidative responses of the tissues of two wild populations of Pelophylax kl. esculentus frogs to heavy metal pollution. AB - Heavy metal pollution of the aquatic environment is of great concern worldwide. Heavy metals are capable of inducing oxidative stress by increasing the formation of reactive oxygen species (ROS), and directly affecting the antioxidant defense system (AOS) in living organisms. The frog Pelophylax kl. esculentus is a semiaquatic species with semipermeable skin and a complex lifecycle, and represents a potentially useful bioindicator organism. The aim of this study was to investigate the accumulation of several heavy metals (Cd, Co, Cr, Cu, Fe, Hg, Ni, Pb and Zn), and their effects on selected parameters of the AOS, including the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), phase II biotransformation enzyme glutathione-S-transferase (GST), the total glutathione (GSH) contents and sulfhydryl (SH) group concentrations, as well as cholinesterases (ChEs) activities in the liver, skin and muscle of P. kl. esculentus. Frog samples were collected at two sites (the Danube-Tisza-Danube canal (DTDC) and the river Ponjavica) in Serbia, which are characterized by different levels of metal pollution. Differences between the metal contents in different tissues showed that the skin of frogs from the DTDC accumulated statistically higher concentrations of Cd, Cu, Pb and Zn, while only the Fe concentration was lower. No significant differences between metal concentrations in muscle tissues of frogs from the DTDC and Ponjavica were observed. Examination of the parameters of the AOS revealed that frogs from the DTDC had higher concentrations of GSH in the liver and of SH groups in the skin and muscle, whereas the activities of the antioxidative enzymes SOD, GHS-Px and GR in the liver and of GR in the skin were lower than in frogs from the Ponjavica. The relationship between metal concentrations and AOS parameters showed the highest number of correlations with GSH, GR and CAT, and with Ni, Zn, Hg, Cr and Cd. Based on the results in this study, we concluded that increased concentrations of heavy metals in frog tissues can alter the AOS, which leads to higher concentrations of GSH and SH groups and lower activities of antioxidative enzymes. The response of the AOS to metal pollutants allowed us to make a distinction between different frog tissues, and to conclude that the liver and skin are more suitable for assessing metal-induced oxidative stress in frogs than muscle. PMID- 26874986 TI - Influence of phosphorus on copper toxicity to Selenastrum gracile (Reinsch) Korshikov. AB - Microalgae need a variety of nutrients for optimal growth and health. However, this rarely occurs in nature, and if nutrient proportions vary, biochemical changes can occur in phytoplankton community. This may result in modifications of zooplankton food quality, affecting aquatic food chains. Our aim was to investigate the toxicity of copper (Cu) to Selenastrum gracile, a common freshwater Chlorophyceae, at different physiological status induced by varying phosphorus (P) concentration in culture medium. Phosphorus was investigated at 2.3*10(-4), 1.1*10(-4), 2.3*10(-5), 4.6*10(-6) and 2.3*10(-6) mol L(-1) and Cu at six concentrations, ranging from 6.9*10(-9) mol L(-1) to 1.0*10(-7) mol L(-1) free Cu(2+) ions. To guarantee the cells would be in a physiological status that reflected the external P concentration, they were previously acclimated up to constant growth rate at each P concentration. Phosphorus acclimated cells were then exposed to Cu and toxicity was evaluated through population density, growth rates and chlorophyll a content. Free Cu(2+) ions concentrations were calculated through the chemical equilibrium model MINEQL(+). The results showed that higher Cu toxicity was obtained in P-limited than in P-replete cells, and that chlorophyll a/cell was higher in P-limited cells and excess Cu than in P-replete cells. This confirms the importance of microalgae nutritional status to withstand the negative effects of the trace metal. PMID- 26874987 TI - Is polycystic ovary syndrome a sexual conflict? A review. AB - Several studies have attempted to explain the high overall prevalence of polycystic ovary syndrome among women worldwide (about 4-10%) despite its link to subfertile phenotypes. For this reason, it is considered an evolutionary paradox. In this review, we show that several genetic loci associated with the disease differently modulate the reproductive parameters of men and women. This observation suggests that such genetic variants lead to opposite effects in the two sexes in reproductive success. Intralocus sexual conflict as a cause of the persistence polycystic ovary syndrome genotypes among humans is supported. PMID- 26874988 TI - Chromosomal analyses of 1510 couples who have experienced recurrent spontaneous abortions. AB - In this retrospective study, karyotype results of 1510 couples with a history of recurrent spontaneous abortion were evaluated. The study was conducted at Balcali Hospital in Adana region of Turkey. For all cases, peripheral blood lymphocytes were cultured for chromosome study using the standard method. Chromosome aberrations were detected in 62 couples (4.1% of all couples). At an individual level, chromosome aberrations were found in a total of 65 cases (41 females and 24 male cases), with structural chromosomal aberrations in 58 cases including balanced translocations in 30 cases, Robertsonian translocations in 12 cases, deletions in seven cases, inversions in nine cases and numerical chromosome aberrations in seven cases. The results of the study indicated that structural aberrations, particularly translocations, were the most common type of aberration observed among couples who had experienced recurrent spontaneous abortions and that these couples might benefit from cytogenetic analyses. PMID- 26874989 TI - Association between premature ovarian failure, polymorphisms in MTHFR and MTRR genes and serum homocysteine concentration. AB - This study investigated the association between premature ovarian failure (POF), MTHFR C677T/A1298C and MTRR A66G genotypes and serum homocysteine (Hcy) concentration. A prospective study was conducted in Chinese women, which included POF patients (n = 180) and controls (n = 195). Peripheral blood samples were used to determine MTHFR C677T/A1298C and MTRR A66G genotypes, and serum Hcy and sex hormone concentrations. Results showed that serum Hcy concentrations of POF patients were significantly higher than those of controls (P < 0.0001). In POF patients, serum Hcy concentrations were significantly correlated with oestradiol and FSH concentrations (r = -0.174, P = 0.037 and r = +0.238, P = 0.006, respectively). There were no significant differences in the distributions of MTHFR C677T/A1298C or MTRR A66G genotypes between the two groups. However, these genetic variants influenced serum Hcy concentrations in POF patients, especially for MTRR 66 AA/AG/GG genotypes, which were significantly correlated with the patients' Hcy concentrations (tau = 0.166, P = 0.033). These results suggest that serum Hcy concentrations in Chinese POF patients are increased and correlated with serum oestradiol/FSH concentrations. In conclusion, MTHFR C667T/A1298C and MTRR A66G genotypes are not associated with POF development, but they affect the patients' serum Hcy concentrations. PMID- 26874990 TI - Positive youth development programmes to reduce substance use in young people: Systematic review. AB - BACKGROUND: Substance use has detrimental short-term and long-term consequences for young people. Positive youth development (PYD) interventions, which favour promotion of positive assets over traditional risk reduction, have received attention recently as a possible intervention to prevent adolescent substance use. We aimed to synthesise the evidence on PYD interventions for reduction in substance use in young people. METHODS: We searched 21 databases, including MEDLINE, PsycINFO, CINAHL and CENTRAL, and hand-searched key journals and websites. We included studies with more than half of participants aged 11-18 years where interventions meeting a pre-specified definition of PYD were delivered in community settings outside of normal school hours and did not target parents or young people with pre-defined conditions. Two reviewers screened records, assessed full-text studies for inclusion, and extracted data. A modified Cochrane risk of bias tool was used for quality assessment. RESULTS: Ten studies reported in 13 reports were included in our synthesis. PYD interventions did not have an effect of statistical or public health significance on any substance use, illicit drug use or alcohol outcomes in young people. CONCLUSIONS: Interventions were diverse in content and delivery. Our review suggests that existing PYD interventions subject to evaluation do not appear to have produced reductions in substance use of public health significance. However, these interventions may not be the best exemplars of a PYD approach. Therefore, our findings should not be taken as evidence for the ineffectiveness of PYD as a theory of change for reducing substance use among young people. Additional rigorous evaluation of PYD interventions is key before further investment. Evaluations were of highly variable quality. Though searches were extensive, we were unable to test for publication bias. PMID- 26874991 TI - Drug use among men by sexual behaviour, race and ethnicity: Prevalence estimates from a nationally representative US sample. PMID- 26874992 TI - Epilepsy through the ages: An artistic point of view. AB - The historical allure of epilepsy transcends academic circles and serves as fascinating critique of the state of the times-its values, judgments, mythos, and people. Immortalized and laid bare in artistic renderings of epilepsy are societal truths, at times both disparately grandiose and grotesque. During the middle ages and Renaissance, the European discourse on epilepsy assumed religious fervor. Epilepsy was considered a demonic machination and its cure an act of divine intercession. A similar theme is found in the artistic depiction of epilepsy from the Inca and Aztec civilizations of that time. After the 19th century drew to a close, the ascendency of empiricism coincided with waning creative interest in epilepsy, with few paintings or pieces to capture insightful perspectives on the illness. In this paper, we review the relationship between art and epilepsy and present two contemporary paintings that convey current western perceptions. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26874993 TI - Pheochromocytoma in a 45 X, iso (Xq) Turner syndrome. PMID- 26874994 TI - Differential expression network analysis for diabetes mellitus type 2 based on expressed level of islet cells. AB - OBJECTIVE: Diabetes mellitus type 2 (T2DM) is a metabolic disease that has become a pressing issue, with potential adverse impact on mental health. We aimed to explore the potential molecular mechanism of T2DM. MATERIAL AND METHODS: GSE38642 microarray data downloaded from gene expression omnibus was used to identify the differentially expressed genes (DEGs). Profiling of complex functionality (ProfCom) was used to analyze the complex function and mine T2DM signature genes. Finally, the differential expression network (DEN) was constructed. RESULTS: We identified 147 DEGs including 59 up- and 88 down-regulated genes. With increasing of degree, the specificity of functional description of DEGs was higher. GO term of "integral to membrane and immune response (not receptor activity) not regulation of immune response" in degree 4 was enriched by 6 DEGs, while the GO term of "immune response" in degree 1 was enriched by 12 DEGs. Two complex functions of integral to membrane an immune response and response to glucose stimulus were enriched by 11 T2DM signature genes including ARG2, GLP1R, PFKFB2, PTPRN, ACSL5, CCR7, IL2RA, IL7R, IL1R2, IL1RL1 and CHST4. Finally, DEN including 11 signature genes and 491 edges was obtained. CONCLUSION: The identified DEGs especially 11 signature genes such as PTPRN, GLP1R, CCR7 and IL2RA may play important roles in the pathogenesis of T2DM. PMID- 26874996 TI - Reply to: Ezetimibe: A real effect? PMID- 26874995 TI - High prevalence of autoimmune thyroid diseases in patients with prolactinomas: A cross-sectional retrospective study in a single tertiary referral centre. AB - BACKGROUND: Prolactin has been shown to exert potent immunomodulatory activities. DESIGN: Retrospective cross-sectional study examining the prevalence of autoimmune thyroid diseases (AITD) in patients with prolactinomas. The medical files of 462 patients (367 women and 95 men) followed up at a single tertiary referral centre were analyzed. RESULTS: The prevalence of AITD among prolactinoma patients was estimated at 21.0% (23.2% in females and 12.6% in males). In 51.5% of the patients, diagnosis of prolactinoma preceded the development of AITD; in 37.2%, both diseases were simultaneously diagnosed and 11.3% of patients were diagnosed first with AITD. Hyperthyroidism was observed in 1.24% of the investigated subjects. Primary hypothyroidism was detected in 15.6% of all patients (16.4% in women; 10.7% in men) with a mean incidence of 24 cases/1000/year. CONCLUSIONS: Our results demonstrate the high frequency of AITD in patients with prolactinomas. The prevalence rate of hyperthyroidism is comparable with the literature data from community-based studies. In contrast, the prevalence of the spontaneous hypothyroidism due to autoimmune thyroiditis is significantly higher in female and male subgroups of patients with prolactinomas in comparison with the general population. A possible role of supraphysiologically increased prolactin levels in the pathogenesis and the clinical course of AITD in patients with prolactinomas can be suggested. Based on these findings we recommend routine screening for AITD with simple thyroid tests (TSH, TPO-Abs and ultrasound examination) in all patients diagnosed with prolactinoma. PMID- 26874997 TI - Stent diameter and type matters in the decision of 6 FR or 7 FR guiding catheter selection during simultaneous kissing stent technique in bifurcation lesions. PMID- 26874998 TI - The Limits of Natural Selection in a Nonequilibrium World. AB - Evolutionary theory predicts that factors such as a small population size or low recombination rate can limit the action of natural selection. The emerging field of comparative population genomics offers an opportunity to evaluate these hypotheses. However, classical theoretical predictions assume that populations are at demographic equilibrium. This assumption is likely to be violated in the very populations researchers use to evaluate selection's limits: populations that have experienced a recent shift in population size and/or effective recombination rates. Here we highlight theory and data analyses concerning limitations on the action of natural selection in nonequilibrial populations and argue that substantial care is needed to appropriately test whether species and populations show meaningful differences in selection efficacy. A move toward model-based inferences that explicitly incorporate nonequilibrium dynamics provides a promising approach to more accurately contrast selection efficacy across populations and interpret its significance. PMID- 26874999 TI - The increasing incidence of paranasal organizing hematoma: a 20-year experience of 23 cases at a single center. AB - BACKGROUND AND OBJECTIVES: Sinonasal organized hematoma is a rare, benign disease that can be locally aggressive and may be mistaken for malignancy. Because of its rarity, the clinical characteristics are not well known. The aim of this study is to investigate the distinguishing features of organized hematoma with an emphasis on incidence change. MATERIALS AND METHODS: In this retrospective study, we reviewed the records of 23 patients with organized hematoma confirmed histopathologically among 5,378 patients who underwent endoscopic sinus surgery performed by a single surgeon from January 1995 to December 2014 at a tertiary care center. Clinical symptoms, endoscopic photography, computed tomography, and operative findings were reviewed. We also reviewed the relevant literature. Age, sex, site, origin subsite and histopathology were investigated. A statistical review was performed using R 3.1.2 to examine incidence change. RESULTS: The most common complaint was frequent epistaxis and nasal obstruction (52.1%). Of the 23 patients, eight were women and 15 were men with an age range of 18 to 75 years. (mean 38.9 years). Nine of these hematomas occurred on the right side and 14 on the left side. The predominant occurrence site was the antrum (65%), followed by the septum (17.3%), inferior turbinate (8%), and ethmoid sinus (8%). The incidence steadily increased over 20 years. CONCLUSION: Investigation of the clinical characteristics and incidence change of organized hematoma can provide useful information. Through analysis of the 23 cases in our study, the age distribution was found to be bimodal and the incidence of organizing hematoma was observed to steadily increase. Clinicians should be aware of these characteristics to avoid misdiagnoses of malignant tumors. PMID- 26875001 TI - Association between Corneal Deformation Amplitude and Posterior Pole Profiles in Primary Open-Angle Glaucoma. AB - PURPOSE: To investigate the relationships between corneal deformation amplitude and posterior pole profiles, including beta-zone parapapillary atrophy (betaPPA), optic disc tilt ratio, torsion degree, and disc-foveal angle, in patients with glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 107 patients with glaucoma. METHODS: Each patient underwent measurement of deformation amplitude with Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany), color optic disc photography, red-free retinal nerve fiber layer photography, axial length measurement, and 24-2 standard automated perimetry. From fundus photographs, the betaPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle were obtained. Pearson's correlation was used to determine the relationships between deformation amplitude and posterior pole profiles. To determine the factors associated with the posterior pole profiles, univariate and multivariate regression analyses were performed. MAIN OUTCOME MEASURES: Deformation amplitude, betaPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle. RESULTS: The study included 50 men (46.7%) and 57 women (53.3%). The mean age was 55.38+/-14.14 years. The mean tilt ratio, torsion degree, and disc-foveal angle were 1.16+/-0.14, 10.26+/-7.63 degrees , and 7.60+/-3.64 degrees , respectively. The mean betaPPA area was 18 211.00+/-28 725.53 pixels. The betaPPA (r = 0.391, P < 0.001) and tilt ratio (r = 0.408, P < 0.001) had significant relationships with deformation amplitude after adjusting for intraocular pressure (IOP). Torsion degree and disc-foveal angle showed no significant relationship with deformation amplitude. The betaPPA area was associated with deformation amplitude and axial length in both univariate (P = 0.008 and 0.006, respectively) and multivariate (P = 0.035 and <0.001, respectively) regression analyses. The tilt ratio was associated with deformation amplitude in univariate regression analysis (P = 0.002), but not in multivariate regression analysis. Axial length was significantly associated with the tilt ratio in both univariate (P < 0.001) and multivariate (P < 0.001) regression analyses. CONCLUSIONS: Deformation amplitude was associated with PPA area and tilt ratio in patients with glaucoma, although in our data set betaPPA area and tilt ratio were not associated with visual field mean deviation. PMID- 26875000 TI - Prevalence of Subretinal Drusenoid Deposits in Older Persons with and without Age Related Macular Degeneration, by Multimodal Imaging. AB - PURPOSE: To assess the prevalence of subretinal drusenoid deposits (SDD) in older adults with healthy maculas and early and intermediate age-related macular degeneration (AMD) using multimodal imaging. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 651 subjects aged >=60 years enrolled in the Alabama Study of Early Age-Related Macular Degeneration from primary care ophthalmology clinics. METHODS: Subjects were imaged using spectral domain optical coherence tomography (SD OCT) of the macula and optic nerve head (ONH), infrared reflectance, fundus autofluorescence, and color fundus photographs (CFP). Eyes were assessed for AMD presence and severity using the Age-Related Eye Disease Study (AREDS) 9-step scale. Criteria for SDD presence were identification on >=1 en face modality plus SD OCT or on >=2 en face modalities if absent on SD OCT. Subretinal drusenoid deposits were considered present at the person level if present in 1 or both eyes. MAIN OUTCOME MEASURES: Prevalence of SDD in participants with and without AMD. RESULTS: Overall prevalence of SDD was 32% (197/611), with 62% (122/197) affected in both eyes. Persons with SDD were older than those without SDD (70.6 vs. 68.7 years, P = 0.0002). Prevalence of SDD was 23% in subjects without AMD and 52% in subjects with AMD (P < 0.0001). Among those with early and intermediate AMD, SDD prevalence was 49% and 79%, respectively. After age adjustment, those with SDD were 3.4 times more likely to have AMD than those without SDD (95% confidence interval, 2.3-4.9). By using CFP only for SDD detection per the AREDS protocol, prevalence of SDD was 2% (12/610). Of persons with SDD detected by SD OCT and confirmed by at least 1 en face modality, 47% (89/190) were detected exclusively on the ONH SD OCT volume. CONCLUSIONS: Subretinal drusenoid deposits are present in approximately one quarter of older adults with healthy maculae and in more than half of persons with early to intermediate AMD, even by stringent criteria. The prevalence of SDD is strongly associated with AMD presence and severity and increases with age, and its retinal topography including peripapillary involvement resembles that of rod photoreceptors. Consensus on SDD detection methods is recommended to advance our knowledge of this lesion and its clinical and biologic significance. PMID- 26875002 TI - Latanoprostene Bunod 0.024% versus Timolol Maleate 0.5% in Subjects with Open Angle Glaucoma or Ocular Hypertension: The APOLLO Study. AB - PURPOSE: To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% every evening (qpm) with timolol maleate 0.5% twice daily (BID) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Phase 3, randomized, controlled, multicenter, double-masked, parallel-group clinical study. PARTICIPANTS: Subjects aged >=18 years with a diagnosis of OAG or OHT in 1 or both eyes. METHODS: Subjects were randomized (2:1) to a 3-month regimen of LBN 0.024% qpm or timolol 0.5% 1 drop BID. Intraocular pressure was measured at 8 am, 12 pm, and 4 pm of each postrandomization visit (week 2, week 6, and month 3). Adverse events were recorded throughout the study. MAIN OUTCOME MEASURES: The primary efficacy end point was IOP in the study eye measured at each of the 9 assessment time points. Secondary efficacy end points included the proportion of subjects with IOP <=18 mmHg consistently at all 9 time points and the proportion of subjects with IOP reduction >=25% consistently at all 9 time points. RESULTS: Of 420 subjects randomized, 387 completed the study (LBN 0.024%, n = 264; timolol 0.5%, n = 123). At all 9 time points, the mean IOP in the study eye was significantly lower in the LBN 0.024% group than in the timolol 0.5% group (P <= 0.002). At all 9 time points, the percentage of subjects with mean IOP <=18 mmHg and the percentage with IOP reduction >=25% were significantly higher in the LBN 0.024% group versus the timolol 0.5% group (mean IOP <=18 mmHg: 22.9% vs. 11.3%, P = 0.005; IOP reduction >=25%: 34.9% vs. 19.5%, P = 0.001). Adverse events were similar in both treatment groups. CONCLUSIONS: In this phase 3 study, LBN 0.024% qpm demonstrated significantly greater IOP lowering than timolol 0.5% BID throughout the day over 3 months of treatment. Latanoprostene bunod 0.024% was effective and safe in these adults with OAG or OHT. PMID- 26875003 TI - A Crossover Design for Comparative Efficacy: A 36-Week Randomized Trial of Bevacizumab and Ranibizumab for Diabetic Macular Edema. AB - PURPOSE: To investigate the comparative efficacy of bevacizumab (Avastin) and ranibizumab (Lucentis; both Genentech, Inc, South San Francisco, CA) for diabetic macular edema (DME) using a crossover study design. DESIGN: Randomized, double masked, 36-week, 3-period crossover clinical trial. PARTICIPANTS: Fifty-six subjects with DME involving the center of the macula in one or both eyes. METHODS: Monthly intravitreous injections of bevacizumab (1.25 mg) or ranibizumab (0.3 mg). MAIN OUTCOME MEASURES: Comparison of mean changes in visual acuity and central retinal thickness, tested using a linear mixed-effects model. RESULTS: Based on the linear mixed-effects model, the 3-month estimated mean improvement in visual acuity was 5.3 letters for bevacizumab and 6.6 letters for ranibizumab (difference, 1.3 letters; P = 0.039). Estimated change in optical coherence tomography (OCT) central subfield mean thickness (CSMT) was -89 MUm for bevacizumab and -137 MUm for ranibizumab (difference, 48 MUm; P < 0.001). Incorporating cumulative treatment benefit, the model yielded a predicted 36-week (9-month) average improvement in visual acuity of 7.1 letters (95% confidence interval [CI], 5.0-9.2) for bevacizumab and 8.4 letters (95% CI, 6.3-10.5) for ranibizumab, and a change in OCT CSMT of -128 MUm (95% CI, -155 to -100) for bevacizumab and -176 MUm (95% CI, -202 to -149) for ranibizumab. There was no significant treatment-by-period interaction (i.e., treatment difference was constant in all 3 periods), nor was there a significant differential carryover effect from one period to the next. CONCLUSIONS: This trial demonstrated a statistically significant but small relative clinical benefit of ranibizumab compared with bevacizumab for treatment of DME, using a markedly reduced sample size relative to a full comparative efficacy study. The effects on visual acuity and central retinal thickness for the 2 drugs are consistent with those reported at 1 year for the concurrent parallel-group trial by the Diabetic Retinopathy Clinical Research Network testing bevacizumab, ranibizumab, and aflibercept for DME. The 3-period crossover design allowed for meaningful and efficient comparison, suggesting that this approach may be useful for future comparative efficacy studies of anti-vascular endothelial growth factor drugs for DME. PMID- 26875004 TI - Retinal and Optic Nerve Hemorrhages in the Newborn Infant: One-Year Results of the Newborn Eye Screen Test Study. AB - PURPOSE: To report the birth prevalence, risk factors, characteristics, and location of fundus hemorrhages (FHs) of the retina and optic nerve present in newborns at birth. DESIGN: Prospective cohort study at Stanford University School of Medicine. PARTICIPANTS: All infants who were 37 weeks postmenstrual age or older and stable were eligible for screening. Infants with known or suspected infectious conjunctivitis were excluded. METHODS: Infants born at Lucile Packard Children's Hospital (LPCH) from July 25, 2013, through July 25, 2014, were offered universal newborn screening via wide-angle digital retinal photography in the Newborn Eye Screen Test study. Maternal, obstetric, and neonatal factors were obtained from hospital records. The location, retinal layer, and laterality of FH were recorded by 1 pediatric vitreoretinal specialist. MAIN OUTCOME MEASURES: Birth prevalence of FH. Secondary outcomes included rate of adverse events, risk factors for FH, hemorrhage characteristics, and adverse events. RESULTS: The birth prevalence of FH in this study was 20.3% (41/202 infants). Ninety-five percent of FHs involved the periphery, 83% involved the macula, and 71% involved multiple layers of the retina. The fovea was involved in 15% of FH cases (birth prevalence, 3.0%). No cases of bilateral foveal hemorrhage were found. Fundus hemorrhages were more common in the left eye than the right. Fundus hemorrhages were most commonly optic nerve flame hemorrhages (48%) and white-centered retinal hemorrhages (30%). Retinal hemorrhages were found most frequently in all 4 quadrants (35%) and more often were multiple than solitary. Macular hemorrhages most often were intraretinal (40%). Among the risk factors examined in this study, vaginal delivery compared with cesarean section (odds ratio [OR], 9.34; 95% confidence interval [CI], 2.57-33.97) showed the greatest level of association with FH. Self-identified ethnicity as Hispanic or Latino showed a protective effect (OR, 0.43; 95% CI, 0.20-0.94). Other study factors were not significant. CONCLUSIONS: Fundus hemorrhages are common among newborns. They often involve multiple areas and layers of the retina. Vaginal delivery was associated with a significantly increased risk of FH, whereas self-identified Hispanic or Latino ethnicity was protective against FH in this study. The long term consequences of FH on visual development remain unknown. PMID- 26875005 TI - Correction of Moderate to High Myopia with a Foldable, Angle-Supported Phakic Intraocular Lens: Results from a 5-Year Open-Label Trial. AB - PURPOSE: To evaluate the 5-year efficacy of a foldable, hydrophobic, angle supported phakic intraocular lens (pIOL) when used to correct moderate to high myopia. DESIGN: Prospective, nonrandomized, multicenter, open-label cohort study conducted in the United States, the European Union, and Canada (3 separate protocols). PARTICIPANTS: This was a pooled analysis of 515 eyes from 360 patients 18 to 49 years of age with moderate to high myopia (preoperative corrected distance visual acuity [CDVA] <=0.34 logarithm of the minimum angle of resolution [logMAR]) and with variance in the manifest refraction spherical equivalent within +/-0.5 diopter (D) for a minimum of 12 months. INTERVENTION: Implantation of the AcrySof Cachet angle-supported anterior chamber pIOL (Alcon Laboratories, Inc., Fort Worth, TX). MAIN OUTCOME MEASURES: Uncorrected distance visual acuity (UDVA), CDVA, predictability and stability of manifest refraction spherical equivalent (MRSE), serious adverse events, endothelial cell density, and patient satisfaction. RESULTS: Of 360 patients who received implantation in at least 1 eye (515 eyes), 326 (90.6%) completed the study (5-year best-corrected visual acuity data available for 415 eyes). At 5 years, a decrease in CDVA of 2 lines or more was observed in 0.5% of eyes (n = 2/415) compared with preoperative baseline. At 5 years, all 415 eyes achieved a CDVA of 0.34 logMAR or less; 91.3% (n = 379/415) had a CDVA of 0.04 logMAR or less. Mean UDVA +/- standard deviation (SD) was 0.01+/-0.18 logMAR; 94.7% (n = 393/415) and 66.3% (n = 275/415) of eyes had a UDVA of 0.34 logMAR or less or 0.04 logMAR or less, respectively, at 5 years. Mean MRSE +/- SD was -0.34+/-0.57 D (range,-2.50 to 1.63 D). Most eyes (89.8%; n = 371/413) had an MRSE within +/-1.00 D of their target refractive error at 5 years and 67.3% (n = 278/413) were within +/-0.50 D. Mean annualized central endothelial cell loss was 1.46% (90% confidence interval [CI], -1.6% to 1.3%) from 6 months to 5 years. The most common pIOL-related serious adverse event was adhesion between the cornea and the iris (synechia; n = 24). Most patients (98.1%) indicated that they would have the same pIOL implanted again. CONCLUSIONS: In patients with moderate to high myopia, the AcrySof Cachet angle supported pIOL provided excellent refractive correction for up to 5 years after implantation, with a low rate of mean central endothelial cell loss. Careful patient selection is necessary to achieve optimal postsurgical outcomes. PMID- 26875006 TI - Lamination of the Outer Plexiform Layer in Optic Atrophy Caused by Dominant WFS1 Mutations. PMID- 26875007 TI - Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. AB - PURPOSE: Myopia is a common cause of vision loss, with uncorrected myopia the leading cause of distance vision impairment globally. Individual studies show variations in the prevalence of myopia and high myopia between regions and ethnic groups, and there continues to be uncertainty regarding increasing prevalence of myopia. DESIGN: Systematic review and meta-analysis. METHODS: We performed a systematic review and meta-analysis of the prevalence of myopia and high myopia and estimated temporal trends from 2000 to 2050 using data published since 1995. The primary data were gathered into 5-year age groups from 0 to >=100, in urban or rural populations in each country, standardized to definitions of myopia of 0.50 diopter (D) or less and of high myopia of -5.00 D or less, projected to the year 2010, then meta-analyzed within Global Burden of Disease (GBD) regions. Any urban or rural age group that lacked data in a GBD region took data from the most similar region. The prevalence data were combined with urbanization data and population data from United Nations Population Department (UNPD) to estimate the prevalence of myopia and high myopia in each country of the world. These estimates were combined with myopia change estimates over time derived from regression analysis of published evidence to project to each decade from 2000 through 2050. RESULTS: We included data from 145 studies covering 2.1 million participants. We estimated 1406 million people with myopia (22.9% of the world population; 95% confidence interval [CI], 932-1932 million [15.2%-31.5%]) and 163 million people with high myopia (2.7% of the world population; 95% CI, 86-387 million [1.4%-6.3%]) in 2000. We predict by 2050 there will be 4758 million people with myopia (49.8% of the world population; 3620-6056 million [95% CI, 43.4%-55.7%]) and 938 million people with high myopia (9.8% of the world population; 479-2104 million [95% CI, 5.7%-19.4%]). CONCLUSIONS: Myopia and high myopia estimates from 2000 to 2050 suggest significant increases in prevalences globally, with implications for planning services, including managing and preventing myopia-related ocular complications and vision loss among almost 1 billion people with high myopia. PMID- 26875008 TI - TERT promoter mutations in melanoma survival. AB - Despite advances in targeted therapies, the treatment of advanced melanoma remains an exercise in disease management, hence a need for biomarkers for identification of at-risk primary melanoma patients. In this study, we aimed to assess the prognostic value of TERT promoter mutations in primary melanomas. Tumors from 300 patients with stage I/II melanoma were sequenced for TERT promoter and BRAF/NRAS mutations. Cumulative curves were drawn for patients with and without mutations with progression-free and melanoma-specific survival as outcomes. Cox proportional hazard regression models were used to determine the effect of the mutations on survivals. Individually, presence of TERT promoter and BRAF/NRAS mutations associated with poor disease-free and melanoma-specific survival with modification of the effect by the rs2853669 polymorphism within the TERT promoter. Hazard ratio (HR) for simultaneous occurrence of TERT promoter and BRAF/NRAS mutations for disease-free survival was 2.3 (95% CI 1.2-4.4) and for melanoma-specific survival 5.8 (95% CI 1.9-18.3). The effect of the mutations on melanoma-specific survival in noncarriers of variant allele of the polymorphism was significant (HR 4.5, 95% CI 1.4-15.2) but could not be calculated for the carriers due to low number of events. The variant allele per se showed association with increased survival (HR 0.3, 95% CI 0.1-0.9). The data in this study provide preliminary evidence that TERT promoter mutations in combination with BRAF/NRAS mutations can be used to identify patients at risk of aggressive disease and the possibility of refinement of the classification with inclusion of the rs2853669 polymorphism within TERT promoter. PMID- 26875009 TI - Children Hospitalized with Rhinovirus Bronchiolitis Have Asthma-Like Characteristics. AB - Children with bronchiolitis often are considered a homogeneous group. However, in a multicenter, prospective study of 2207 young children hospitalized for bronchiolitis, we found that children with respiratory syncytial virus detected differ from those with rhinovirus detected; the latter patients resemble older children with asthma, including more frequent treatment with corticosteroids. PMID- 26875010 TI - Acute Appendicitis-An Unexpected Etiology. PMID- 26875012 TI - Reply to Letter From Campbell-Questionable Scientific Basis for Radical Dietary Sodium Recommendations. PMID- 26875011 TI - Executive Functioning and School Performance among Pediatric Survivors of Complex Congenital Heart Disease. AB - OBJECTIVE: To investigate the presence and severity of real-world impairments in executive functioning-responsible for children's regulatory skills (metacognition, behavioral regulation)-and its potential impact on school performance among pediatric survivors of complex congenital heart disease (CHD). STUDY DESIGN: Survivors of complex CHD aged 8-16 years (n = 143) and their parents/guardians from a regional CHD survivor registry participated (81% participation rate). Parents completed proxy measures of executive functioning, school competency, and school-related quality of life (QOL). Patients also completed a measure of school QOL and underwent IQ testing. Patients were categorized into 2 groups based on heart lesion complexity: 2-ventricle or single ventricle. RESULTS: Survivors of complex CHD performed significantly worse than norms for executive functioning, IQ, school competency, and school QOL. Metacognition was more severely affected than behavioral regulation, and metacognitive deficits were more often present in older children. Even after taking into account demographic factors, disease severity, and IQ, metacognition uniquely and strongly predicted poorer school performance. In exploratory analyses, patients with single-ventricle lesions were rated as having lower school competency and school QOL, and patients with 2-ventricle lesions were rated as having poorer behavioral regulation. CONCLUSIONS: Survivors of complex CHD experience greater executive functioning difficulties than healthy peers, with metacognition particularly impacted and particularly relevant for day-to-day school performance. Especially in older children, clinicians should watch for metacognitive deficits, such as problems with organization, planning, self monitoring, and follow-through on tasks. PMID- 26875013 TI - Differentiating Exercise-Induced Cardiac Adaptations From Cardiac Pathology: The "Grey Zone" of Clinical Uncertainty. AB - Exercise-induced cardiac remodelling (EICR) refers to the cardiac structural and functional adaptations that occur in response to the hemodynamic stress of strenuous exercise. Differentiating physiological cardiac hypertrophy as a result of EICR from structural cardiac pathology may be challenging in clinical practice because of the phenotypic crossover between extreme forms of the "hearts of athletes" and mild forms of cardiomyopathy. This structural phenotypic overlap equates to a grey zone of clinical uncertainty. Specifically, asymptomatic athletes presenting with extreme left ventricular (LV) dilatation, LV wall thickening, or right ventricular (RV) dilatation require a systematic and integrative diagnostic approach to achieve accurate clinical differentiation. The combination of a careful clinical history and examination, appropriately used multimodality cardiac imaging, functional exercise testing, ambulatory rhythm monitoring, and occasional detraining typically provides the necessary data for diagnostic purposes and sports participation recommendations. Further clinical distinction of the hearts of athletes from cardiac pathology may emerge from future clinical and translational research efforts establishing exercise-related biomarker profiles and mechanisms underlying EICR adaptations. PMID- 26875014 TI - The Demise of Morphine Oxygen Nitroglycerin Aspirin (MONA). PMID- 26875015 TI - Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts. AB - BACKGROUND: Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. METHODS: Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. RESULTS: Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (alphaSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the alphaSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. CONCLUSIONS: PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. PMID- 26875016 TI - Exercise Intolerance in Heart Failure: Did We Forget the Brain? AB - Exercise tolerance is affected in patients with heart failure (HF). Although the inability of the heart to pump blood to the working muscle has been the conventional mechanism proposed to explain the lowered capacity of patients with HF to exercise, evidence suggests that the pathophysiological mechanisms associated with their exercise intolerance is more complex. Recent findings indicate that lowered cerebral blood flow (CBF) and oxygenation likely represent limiting factors for exercise capacity in patients with HF. After an overview of cardiac and peripheral responses during acute and chronic exercise in healthy individuals, we succinctly review cardiac and noncardiac mechanisms by which HF influences exercise tolerance. We then consider how HF, comorbidity, and HF treatment influence CBF and oxygenation at rest and during exercise. Finally, we provide suggestions for further research to improve our understanding of the role of the brain in exercise intolerance in HF. PMID- 26875017 TI - Questionable Scientific Basis for Relaxed Dietary Sodium Recommendations. PMID- 26875018 TI - In situ hybridization chain reaction mediated ultrasensitive enzyme-free and conjugation-free electrochemcial genosensor for BRCA-1 gene in complex matrices. AB - In this study, we report an enzyme-free and conjugation-free electrochemical genosensor enabling an ultrasensitive readout of BRCA-1, a breast cancer susceptibility gene. The sensor employs a target-responsive hybridization chain reaction (HCR) to significantly amplify the detectable current signals. By means of a functional auxiliary probe pair and a versatile initiator sequence, a linear DNA concatemer structure can be formed via spontaneous and continuous polymerization of DNA oligomers in the presence of target sequence. Such a DNA nanoassembly endows the genosensor an ultrahigh sensitivity up to 1 aM, which is higher than that of the nanomaterials-based or enzyme mediated amplification approaches by several orders of magnitude. More importantly, the sensor's responsive peak current exhibits a favorable linear correlation to the logarithm of the concentrations of target sequence ranging from 1 aM to 10 pM. In addition, the sensor is highly selective, and can discriminate a single mismatched sequence. This HCR-based genosensor is also capable of probing low-abundance BRCA 1 gene sequence directly in complex matrices, such as 50% human serum, with minimal interference. These advantages will make our tailor-engineered HCR-based electrochemical genosensor appealing to genetic analysis and clinical diagnostics. PMID- 26875019 TI - Key Factors Associated with Major Depression in a National Sample of Stroke Survivors. AB - BACKGROUND: Depression, one of the most common complications encountered after stroke, is associated with poorer outcomes. The aim of this study was to determine the factors independently associated with and predictive of poststroke depression (PSD). METHODS: We assessed the prevalence of depression (Patient Health Questionnaire [PHQ-8] score >10) among a national sample of adults (>=20 years) with stroke who participated in the National Health and Nutrition Examination Surveys from 2005 to 2010. Logistic regression and random forest models were used to determine the factors associated with and predictive of PSD, after adjusting for sociodemographic and clinical factors. RESULTS: Of the 17,132 individuals surveyed, 546 stroke survivors were screened for depression, and 17% had depression, corresponding to 872,237 stroke survivors with depression in the United States. In the logistic regression model, after adjustment for sociodemographic variables, poverty (poverty index <200% versus >=200%, odds ratio [OR] 2.61, 95% confidence interval [CI] 1.23-5.53) and 3 or more medical comorbidities (OR 1.59, 95% CI 1.01-2.49) were associated with higher odds of PSD; increasing age was associated with lower odds of PSD (per year OR .95, 95% CI .94-.97). In the random forest model, the 10 most important factors predictive of PSD were younger age, lower education level, higher body mass index, black race, poverty, smoking, female sex, single marital status, lack of cancer history, and previous myocardial infarction (specificity = 70%, sensitivity = 64%). CONCLUSION: Although numerous factors were predictive of developing PSD, younger age, poverty, and multiple comorbidities were strong and independent factors. More aggressive screening for depression in these individuals may be warranted. PMID- 26875020 TI - Autoimmune diseases and myelodysplastic syndromes. AB - Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with >=5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. PMID- 26875021 TI - The Predictors of Diet Quality among Australian Children Aged 3.5 Years. AB - BACKGROUND: It is critical to promote healthy eating early in life. OBJECTIVE: The aim of this study was to examine diet quality and its predictors among Australian preschool-aged children. DESIGN: Diet was assessed at age 3.5 years using multiple 24-hour recalls. Diet quality was assessed using an adapted version of the Revised Children's Diet Quality Index (RC-DQI). Potential predictors of diet quality were from questionnaires at age 3, 9, and 18 months and informed by the ecologic model of childhood overweight. Potential predictors included child's sex, age of introduction to solid foods, breastfeeding status, food acceptance, maternal nutrition knowledge, modeling of healthy eating, self efficacy, education, and home food availability. PARTICIPANTS: Data from 244 children participating in the Melbourne Infant Feeding, Activity, and Nutrition Trial in 2008-2010 and follow-up data collection in 2011-2013 were examined. MAIN OUTCOME MEASURES: Diet quality at age 3.5 years. STATISTICAL ANALYSES PERFORMED: Bivariate logistic regression was performed to assess the relationship between diet quality and each predictor. A multivariable logistic regression model accounting for influences of covariates, treatment arm, and clustering by group tested associations between diet quality and significant predictors from bivariate analyses. RESULTS: RC-DQI scores had a mean+/-standard deviation score of 62.8+/-8.3 points out of a maximum of 85 points. Breastfeeding status (odds ratio [OR] 2.34, 95% CI 1.33 to 4.10) and maternal modeling of healthy eating (OR 1.75, 95% CI 1.01 to 3.03) were positively associated with RC-DQI scores. Both breastfeeding status (OR 3.09, 95% CI 1.63 to 5.85) and modeling (OR 2.01, 95% CI 1.04 to 3.88) remained positively associated with diet quality after adjustment for child age, body mass index z score, energy intake, treatment arm, and clustering. CONCLUSIONS: Breastfeeding status and modeling of healthy eating were independently associated with children's diet quality. Early intervention could assist mothers to practice these behaviors to provide support for improving child diet quality. PMID- 26875022 TI - Factors Associated with Self-Reported Menu-Labeling Usage among US Adults. AB - BACKGROUND: Menu labeling can help people select foods and beverages with fewer calories and is a potential population-based strategy to reduce obesity and diet related chronic diseases in the United States. OBJECTIVE: The aim of this cross sectional study was to examine the prevalence of menu-labeling use among adults and its association with sociodemographic, behavioral, and policy factors. METHODS: The 2012 Behavioral Risk Factor Surveillance System data from 17 states, which included 100,141 adults who noticed menu labeling at fast-food or chain restaurants ("When calorie information is available in the restaurant, how often does this information help you decide what to order?") were used. Menu-labeling use was categorized as frequent (always/most of the time), moderate (half the time/sometimes), and never. Multinomial logistic regression was used to examine associations among sociodemographic, behavioral, and policy factors with menu labeling use. RESULTS: Overall, of adults who noticed menu labeling, 25.6% reported frequent use of menu labeling, 31.6% reported moderate use, and 42.7% reported that they never use menu labeling. Compared with never users, frequent users were significantly more likely to be younger, female, nonwhite, more educated, high-income, adults who were overweight or obese, physically active, former- or never-smokers, less than daily (<1 time/day) consumers of sugar sweetened beverage, and living in states where menu-labeling legislation was enacted or proposed. CONCLUSIONS: Menu labeling is one method that consumers can use to help reduce their calorie consumption from restaurants. These findings can be used to develop targeted interventions to increase menu-labeling use among subpopulations with lower use. PMID- 26875023 TI - Associations among Nine Family Dinner Frequency Measures and Child Weight, Dietary, and Psychosocial Outcomes. AB - BACKGROUND: Family meal frequency has been consistently and significantly associated with positive youth dietary and psychosocial outcomes, but less consistently associated with weight outcomes. Family meal frequency measurement has varied widely and it is unclear how this variation might impact relationships with youth weight, dietary, and psychosocial outcomes. OBJECTIVE: This study assesses how five parent/caregiver-reported and four child-reported family dinner frequency measures correlate with each other and are associated with health related outcomes. DESIGN/PARTICIPANTS: This secondary, cross-sectional analysis uses baseline, parent/caregiver (n=160) and 8- to 12-year-old child (n=160) data from the Healthy Home Offerings via the Mealtime Environment (HOME) Plus trial (collected 2011 to 2012). Data were obtained from objective measurements, dietary recall interviews, and psychosocial surveys. OUTCOME MEASURES: Outcomes included child body mass index z scores (BMIz); fruit, vegetable, and sugar-sweetened beverage intake; dietary quality (Healthy Eating Index-2010); family connectedness; and meal conversations. STATISTICAL ANALYSES PERFORMED: Pearson correlations and general linear models were used to assess associations between family dinner frequency measures and outcomes. RESULTS: All family dinner frequency measures had comparable means and were correlated within and across parent/caregiver and child reporters (r=0.17 to 0.94; P<0.01). In unadjusted analyses, 78% of family dinner frequency measures were significantly associated with BMIz and 100% were significantly associated with fruit and vegetable intake and Healthy Eating Index-2010. In adjusted models, most significant associations with dietary and psychosocial outcomes remained, but associations with child BMIz remained significant only for parent/caregiver- (beta+/-standard error=-.07+/ .03; P<0.05) and child-reported (beta+/-standard error=-.06+/-.02; P<0.01) family dinner frequency measures asking about "sitting and eating" dinner. CONCLUSIONS: Despite phrasing variations in family dinner frequency measures (eg, which family members were present and how meals were occurring), few differences were found in associations with dietary and psychosocial outcomes, but differences were apparent for child BMIz, which suggests that phrasing of family dinner frequency measures can influence associations found with weight outcomes. PMID- 26875025 TI - [Not Available]. PMID- 26875026 TI - [Not Available]. PMID- 26875024 TI - Interactions between levels of attention ability and levels of bilingualism in children's executive functioning. AB - Attention difficulty is associated with poor performance on executive functioning (EF) tasks, yet EF is enhanced in bilingual children. However, no research to date has investigated the possible interaction between bilingualism and attention ability in children to determine the consequences for EF when both are present. We assessed a sample of typically developing children who were 8 to 11 years old for their ability in attention control and level of bilingualism on the basis of questionnaires completed by parents and teachers. Children performed three tasks requiring aspects of EF: stop signal task (inhibition), flanker task (interference control), and frogs matrices task (spatial working memory). Results from hierarchical regressions confirmed that both attention ability and bilingualism contributed to performance on the EF tasks. Where interaction effects were significant, they showed that attention ability was a stronger predictor for an inhibition task, namely stop signal, and bilingualism a stronger predictor for an interference task, namely flanker. Furthermore, these results allow us to discuss the relation between EF and attention ability. PMID- 26875027 TI - [Not Available]. PMID- 26875028 TI - Patient participation - What is it? PMID- 26875029 TI - [Not Available]. PMID- 26875030 TI - What kind of health economics do we need? PMID- 26875031 TI - [Not Available]. PMID- 26875032 TI - [Not Available]. PMID- 26875033 TI - Taking up national safety alerts to improve patient safety in hospitals: The perspective of healthcare quality and risk managers. AB - BACKGROUND: National safety alert systems publish relevant information to improve patient safety in hospitals. However, the information has to be transformed into local action to have an effect on patient safety. We studied three research questions: How do Swiss healthcare quality and risk managers (qm/rm(1)) see their own role in learning from safety alerts issued by the Swiss national voluntary reporting and analysis system? What are their attitudes towards and evaluations of the alerts, and which types of improvement actions were fostered by the safety alerts? METHODS: A survey was developed and applied to Swiss healthcare risk and quality managers, with a response rate of 39 % (n=116). Descriptive statistics are presented. RESULTS: The qm/rm disseminate and communicate with a broad variety of professional groups about the alerts. While most respondents felt that they should know the alerts and their contents, only a part of them felt responsible for driving organizational change based on the recommendations. However, most respondents used safety alerts to back up their own patient safety goals. The alerts were evaluated positively on various dimensions such as usefulness and were considered as standards of good practice by the majority of the respondents. A range of organizational responses was applied, with disseminating information being the most common. An active role is related to using safety alerts for backing up own patient safety goals. CONCLUSIONS: To support an active role of qm/rm in their hospital's learning from safety alerts, appropriate organizational structures should be developed. Furthermore, they could be given special information or training to act as an information hub on the issues discussed in the alerts. PMID- 26875034 TI - [Involving patients, the insured and the general public in healthcare decision making]. AB - No doubt, the public should be involved in healthcare decision making, especially when decision makers from politics and self-government agencies are faced with the difficult task of setting priorities. There is a general consensus on the need for a stronger patient centeredness, even in HTA processes, and internationally different ways of public participation are discussed and tested in decision making processes. This paper describes how the public can be involved in different decision situations, and it shows how preference measurement methods are currently being used in an international context to support decision making. It distinguishes between different levels of decision making on health technologies: approval, assessment, pricing, and finally utilization. The range of participation efforts extends from qualitative surveys of patients' needs (Citizen Councils of NICE in the UK) to science-based documentation of quantitative patient preferences, such as in the current pilot projects of the FDA in the US and the EMA at the European level. Possible approaches for the elicitation and documentation of preference structures and trade-offs in relation to alternate health technologies are decision aids, such as multi-criteria decision analysis (MCDA), that provide the necessary information for weighting and prioritizing decision criteria. PMID- 26875035 TI - [Patient attitudes and expectations towards conflicts of interest of attending physicians]. AB - BACKGROUND: Patients can truly expect to be treated by their physicians without undue influences of secondary interests. It is not known what patients in Germany know about relationships between physicians and the pharmaceutical industry and if and how they want to be informed about these relationships. METHOD: An information sheet explaining conflicts of interest and a 19-item questionnaire were distributed to 765 patients at various medical offices and hospitals in two German cities. 80 % (n=612) of the patients completed and returned the questionnaires anonymously. RESULTS: 65 % of the patients did not know of conflicts of interest (COI) doctors may have with the pharmaceutical industry. 74 % of the patients would like to know if their doctor had obtained any benefits through contacts with the pharmaceutical industry. 71 % agreed that a disclosure would increase their confidence, and 74 % wanted their physicians to declare COI verbally to them during a consultation. 40 % would prefer a doctor who is not receiving any benefits from the pharmaceutical industry. The desire for disclosure was significantly higher in patients who had an awareness of the problems of COI (OR 4.95; 95 % CI 3.33 - 7.35). However, 35 % of the patients trusted their attending physicians anyway and did not see a need for disclosure of any COI. CONCLUSION: The majority of patients, but not all patients want to be informed about COI of their physicians. The best way to do this has yet to be determined. PMID- 26875036 TI - [A pilot study to evaluate the DMP for coronary heart disease - Development of a methodology and first results]. AB - Regarding the effectiveness of disease management programs (DMPs) in Germany, several studies have been published on the DMP for type 2 diabetes. This pilot study provides methodological insights into evaluating the DMP for coronary heart disease (CHD), which currently includes 1.7 million participants, and reveals trends in healthcare outcomes for mortality, guideline adherent prescribing and costs. Major methodological challenges that need to be considered for the development of an appropriate matching method for this indication have been identified. The results show positive trends in favor of the DMP regarding mortality, costs and medication according to guidelines. A matching design is applicable to the CHD indication; the knowledge gained regarding the quality of care can be used for a targeted development of the program. PMID- 26875037 TI - [Conflict of interest in continuing medical education - Studies on certified CME courses]. AB - OBJECTIVES: Although the problem of conflict of interest in medical education is discussed intensively, few valid data have been published on how to deal with the form, content, funding, sponsorship, and the influence of economic interests in continuing medical education (CME). Against this background, we carried out an analysis of data which had been documented for the purpose of certification by a German Medical Association. A central aim of the study was to obtain evidence of possible influences of economic interests on continuing medical education. Furthermore, strategies for quality assurance of CME contents and their implementation were to be examined. METHODS: We analyzed all registration data for courses certified in the category D ("structured interactive CME via print media, online media and audiovisual media") by the Bavarian Chamber of Physicians in 2012. To measure the effects of conflict of interest, relationships between topics of training and variables relating to the alleged self-interest of the organizer/sponsor (for example, drug sales in a group of physicians) were statistically verified. These data were taken from the Bavarian Medical Statistics 2012 and the GKV-Arzneimittelschnellinformation. RESULTS: In 2012, a total of 734 CME course offerings have been submitted for 51 medical specialties by 30 course suppliers in the Bavarian Medical Association. To ensure the neutrality of interests of the CME courses the course suppliers signed a cooperation treaty ensuring their compliance with defined behavior towards the Bavarian Medical Association concerning sponsorship. The correlation between course topics and drug data suggests that course suppliers tend to submit topics that are economically attractive to them. There was a significant correlation between the number of CME courses in a specific field and the sales from drug prescriptions issued by physicians in the respective field. CONCLUSIONS: The results show that neutrality of interests regarding continuing medical education is difficult to achieve under the current framework for the organization, certification, and especially the funding of CME events in Germany. The cooperation agreement between the Bavarian Medical Association and training applicants is taken as an example of how legal certainty can be ensured. Based on the findings described below, suggestions and strategies to strengthen assessment expertise of course participants have been developed and elaborated. PMID- 26875038 TI - [On the way to becoming an MD (Dr. med.): What kind of support do doctoral students need? Part 1: Survey and development of a program]. AB - In Germany, medical doctorates are regularly criticized for their insufficient quality. In order to improve the quality of doctorates and to support doctoral candidates, a department-wide doctoral research program was established at the Goethe University of Frankfurt am Main in 2011 taking into account the practical needs of doctoral students at the School of Medicine. The program development proceeded in several steps: in the first step (2009/2010), a pilot study with eleven doctoral candidates was carried out at the Institute of General Practice. Their ratings of the perceived relevance and their own knowledge of 15 topics of scientific work were used to identify a provisional need for support. Subsequently an interdisciplinary panel of experts established the program throughout the faculty. Since its implementation, a requirements analysis in the form of questionnaires has been continuously carried out in order to assess the doctoral students' prior knowledge and their preferences expressed. At the same time, systematic searches for support programs in other medical fields have been conducted throughout Germany on several occasions. On the basis of the pilot study, the research results and the expert panel discussions the following topics were found to be particularly relevant: principles of good scientific practice, literature search, reference management, organization and structure of a doctoral thesis, formatting of Word documents, clinical epidemiology and data management. A specific, stepwise development process was used to design a concept for the faculty of medicine that pays close attention to the knowledge and interests of doctoral candidates. The establishment of the doctoral research program in Frankfurt and the results of its evaluation are presented in a second article (Paulitsch et al., 2016). PMID- 26875039 TI - [On the way to becoming an MD (Dr. med.): What kind of support do doctoral students need? Part 2: Establishing the program]. AB - The poor quality of medical dissertations has repeatedly been criticized by scientific and higher education institutions. In medicine, doctoral students rated their own knowledge of fundamental scientific issues as low. The establishment of a doctoral research program could solve this problem. However, no scientific paper has yet been published showing how such support programs should be designed. Here we present an example of such a design on the basis of the doctoral research program which the Faculty of Medicine at the Goethe University, Frankfurt am Main, established in 2011. Using requirements analyses, eight basic courses have been developed that can be attended separately but are considered to contain essential information for all doctorates. To ensure a high quality of the doctoral research program and to take into account the needs of doctoral students, both the individual courses and the doctoral research program as a whole were evaluated. The doctoral research program has been very well accepted by doctoral students, with a total of 449 doctoral students, who attended an average of five courses from 2011 to 2014. The total number of participants amounted to 2,302 in 159 courses. The results of the evaluation show that on average all the basic courses were considered to be 'good' or 'very good'. After participating in eight courses, the doctoral students' overall evaluation of the doctoral research program resulted in a very positive assessment of the overall concept. Further aspects, such as the examination of the impact of participation in the doctoral research program on dissertation quality, are pending. Due to the positive feedback from participants, we recommend that other faculties establish similar programs. PMID- 26875040 TI - [Good practice guidelines for health information]. AB - Evidence-based health information is distinguished by the provision of an unbiased and trustworthy description of the current state of medical knowledge. It enables people to learn more about health and disease, and to make health related decisions - on their own or together with others - reflecting their attitudes and lifestyle. To adequately serve this purpose, health information must be evidence-based. A working group from the German Network for Evidence based Medicine (Deutsches Netzwerk Evidenzbasierte Medizin) has developed a first draft of good practice guidelines for health information (Gute Praxis Gesundheitsinformation) with the aim of providing support for authors and publishers of evidence-based health information. The group included researchers, patient representatives, journalists and developers of health information. The criteria for evidence-based health information were developed and agreed upon within this author group, and then made available for public comment. All submitted comments were documented and assessed regarding the need to revise or amend the draft. Changes were subsequently implemented following approval by the author group. Gute Praxis Gesundheitsinformation calls for a transparent methodological approach in the development of health information. To achieve this, evidence-based information must be based on (a) a systematic literature search, (b) a justified selection of evidence, (c) unbiased reporting of relevant results, (d) appropriate factual and linguistic communication of uncertainties, (e) either avoidance of any direct recommendations or a strict division between the reporting of results and the derivation of recommendations, (f) the consideration of current evidence on the communication of figures, risks and probabilities, and (g) transparent information about the authors and publishers of the health information, including their funding sources. Gute Praxis Gesundheitsinformation lists a total of 16 aspects to be addressed in methods papers. Gute Praxis Gesundheitsinformation is a tool that puts forward methodological aspects to be considered when developing health information. In order to be transparent, descriptions of the underlying methods and processes need to be published in easily accessible methods papers describing the general procedure. PMID- 26875041 TI - [Not Available]. PMID- 26875042 TI - [Not Available]. PMID- 26875043 TI - Spanish multicentre PIBHE study: Prevalence and immunization of chronic hepatitis B in haemodialysis patients in Spain. AB - INTRODUCTION: The PIBHE study, promoted by the Spanish Liver and Kidney Association and the Dialysis Virus Group of the Spanish Society of Nephrology, is the first study to determine the status of haemodialysis patients with chronic HBV infection and the immunisation against the vaccine. METHOD: The study has a national multicentre, observational, cross-sectional design and was carried out between January 2013 and 2014. A data collection folder was sent to all the nephrology departments and outpatient haemodialysis units in Spain, to be completed based on patient medical files after informed consent. The data were recorded in a central database. RESULTS: A total of 215 centres participated (15,645 patients), with an HBV prevalence of 1.03%. HCV or HIV was present in 7.2% of the HBV(+) patients. Viral load was below 2,000 IU/ml in 80%. GOT and GPT levels were 19.1+/-10.1 and 15.9+/-9.6 IU/ml, respectively. Liver biopsy was performed in 7.1%. Antiviral treatment was prescribed in 30% and suspended in 12.5%: entecavir (13.3%), lamivudine (10%), adefovir and tenofovir (6.7%), and interferon (3.3%). A total of 34.5% were candidates for renal transplantation and 6.9% had not been evaluated; 64.3% were followed up by a gastroenterologist; 27.2% of HBV(-) patients without immunisation had not been vaccinated. Fourteen different immunisation schedules had been used, with an immunisation rate of 58.8%. Mean anti-HBs stood at 165.7+/-297.8mIU/ml. A total of 72.7% of patients had received a vaccination course; 26.4%, 2 cycles; 1.0%, 3 cycles; and 11.6%, a booster dose. A total of 28.3% had a poor response (anti-HBs 10-99mIU/ml); 22.4%, an optimal response (anti-HBs 100-999mIU/ml); and 7.9%, an excellent response (anti-HBs >= 1,000mIU/ml). Age was significantly associated with response to vaccination; the mean age of nonresponders was significantly higher than patients who had a response of any kind (P<.05). The highest probability of an immune response was achieved with 4 doses of 40 mcg of adjuvanted vaccine (OR: 7.3; 95% CI 3.4 to 15.7), for the same age and number of cycles and boosters. Age, adjuvanted vaccine, dose and vaccination schedule influenced the immune response and the anti-HBs titres reached (P<.05). CONCLUSION: The prevalence of chronic HBV infection in haemodialysis in Spain is low and so are the rates of immunisation against the virus. The vaccination schedules used are very diverse and have been observed to correlate with the immune response. It would therefore be necessary to establish a protocol for the most effective vaccination schedule to increase immunisation in these patients. PMID- 26875044 TI - Association between ADAM12 polymorphism and knee osteoarthritis in Thai population. AB - BACKGROUND: Osteoarthritis (OA), a common degenerative joint disorder in the elderly, is characterized by the destruction of articular cartilage, bony outgrowths at joint margins, and synovitis. The objective of this study was to evaluate whether there is an association between the ADAM12 (rs3740199) polymorphism and susceptibility to knee OA in a Thai population. METHODS: Genomic deoxyribonucleic acid (DNA) was isolated from 200 Thai knee OA patients and 200 healthy controls. High resolution melting analysis was used to detect ADAM12 polymorphisms. The melt profile of all DNA samples was generated on the CFX96TM real-time polymerase chain reaction system and analyzed by Precision Melt AnalysisTM software. The genotype distributions and allele frequencies of ADAM12 were compared between groups using the StatCalc program. RESULTS: The significant associations were shown from the C allele (OR=2.10, 95% CI=1.16-3.79, P=0.008) and the CC genotype (OR=4.28, 95% CI=1.21-15.72, P=0.01) in male knee OA patients. No significant association was observed in female patients. CONCLUSION: The rs3740199 in ADAM12 was associated with knee OA susceptibility in Thai male patients, and individuals with the CC genotype carried the highest risk when compared with the GG and GC genotypes. CLINICAL RELEVANCE: The rs3740199 polymorphism of the ADAM12 gene can potentially be used to determine genetically high-risk subgroup of knee osteoarthritis and to better understand the pathogenesis of knee osteoarthritis. PMID- 26875046 TI - What are the bias, imprecision, and limits of agreement for finding the flexion extension plane of the knee with five tibial reference lines? AB - BACKGROUND: Internal-external (I-E) malrotation of the tibial component is associated with poor function after total knee arthroplasty (TKA). Kinematically aligned (KA) TKA uses a functionally defined flexion-extension (F-E) tibial reference line, which is parallel to the F-E plane of the extended knee, to set I E rotation of the tibial component. METHODS: Sixty-two, three-dimensional bone models of normal knees were analyzed. We computed the bias (mean), imprecision (+/-standard deviation), and limits of agreement (mean+/-2 standard deviations) of the angle between five anatomically defined tibial reference lines used in mechanically aligned (MA) TKA and the F-E tibial reference line (+external). RESULTS: The following are the bias, imprecision, and limits of agreement of the angle between the F-E tibial reference line and 1) the tibial reference lines connecting the medial border (-2 degrees +/-6 degrees , -14 degrees to 10 degrees ), medial 1/3 (6 degrees +/-6 degrees , -6 degrees to 18 degrees ), and the most anterior point of the tibial tubercle (9 degrees +/-4 degrees , -1 degrees to 17 degrees ) with the center of the posterior cruciate ligament, and 2) the tibial reference lines perpendicular to the posterior condylar axis of the tibia (-3 degrees +/-4 degrees , -11 degrees to 5 degrees ), and a line connecting the centers of the tibial condyles (1 degrees +/-4 degrees , -7 degrees to 9 degrees ). CLINICAL RELEVANCE: Based on these in vitro findings, it might be prudent to reconsider setting the I-E rotation of the tibial component to tibial reference lines that have bias, imprecision, and limits of agreement that fall outside the -7 degrees to 10 degrees range associated with high function after KA TKA. PMID- 26875045 TI - Contribution of altered hip, knee and foot kinematics to dynamic postural impairments in females with patellofemoral pain during stair ascent. AB - BACKGROUND: Altered hip, knee and foot kinematics have been systematically observed in individuals with patellofemoral pain (PFP). However, less attention has been given to the altered dynamic postural control associated with PFP. Additionally, the relative contribution of kinematic impairments to the postural behavior of subjects with PFP remains an open question that warrants investigation. The aims of this study were: i) to investigate possible differences in hip adduction, rearfoot eversion, knee flexion and displacement area of the center of pressure (COP) in individuals with PFP in comparison to controls during stair ascent; and (ii) to determine which kinematic parameter is the best predictor of the displacement area of the COP measured during the stance phase of the stair ascent. METHODS: Twenty-nine females with PFP and 25 asymptomatic pain-free females underwent three-dimensional kinematic and COP analyses during stair ascent. Between-group comparisons were made using independent t-tests. Regression models were performed to identify the capability of each kinematic factor in predicting the displacement area of the COP. RESULTS: Reduced knee flexion and displacement area of the COP as well as increased peak hip adduction and peak rearfoot eversion were observed in individuals with PFP as compared to controls. Peak hip adduction was the best predictor of the displacement area of the COP (r(2)=23.4%). CONCLUSIONS: The excessive hip adduction was the biggest predictor of the displacement area of the COP. CLINICAL RELEVANCE: Based on our findings, proximally targeted interventions may be of major importance for the functional reestablishment of females with PFP. PMID- 26875047 TI - The influence of intraoperative soft tissue balance on patellar pressure in posterior-stabilized total knee arthroplasty. AB - BACKGROUND: Appropriate soft tissue balance is essential for the success of total knee arthroplasty (TKA), and assessment with an offset-type tensor provides useful information about the femorotibial (FT) joint. The purpose of the study was to investigate the relationship between intraoperative soft tissue balance and patellar pressure at both medial and lateral sides. METHODS: Thirty varus type osteoarthritis patients who received mobile-bearing posterior-stabilized TKAs were enrolled in the study. Using the tensor, soft tissue balance, including joint component gap and varus ligament balance, was recorded at 0 degrees , 10 degrees , 30 degrees , 60 degrees , 90 degrees , 120 degrees , and 135 degrees with patellofemoral (PF) joint reduction and femoral component placement. Following final prostheses implanted with appropriate insert, the medial and lateral patellar pressures were measured at each flexion angle. A simple regression analysis was performed between each patellar pressure, parameter of soft tissue balance, and postoperative flexion angle. RESULTS: Both lateral and medial patellar pressures increased with flexion. The lateral patellar pressure was significantly higher than the medial patellar pressure at 60 degrees , 90 degrees , and 135 degrees of flexion (p<0.05). The lateral patellar pressure inversely correlated with the varus ligament balance at 60 degrees and 90 degrees of flexion (p<0.05). The lateral patellar pressure at 120 degrees and 135 degrees of flexion inversely correlated with the postoperative flexion angle (p<0.05). CONCLUSION: Soft tissue balance influenced patellar pressure. In particular, a reduced lateral patellar pressure was found at the lateral laxity at flexion, leading to high postoperative flexion angle. LEVEL OF EVIDENCE: III. PMID- 26875048 TI - Primary and coupled motions of the native knee in response to applied varus and valgus load. AB - BACKGROUND: Knowledge of the complex kinematics of the native knee is a prerequisite for a successful reconstructive procedure. The aim of this study is to describe the primary and coupled motions of the native knee throughout the range of knee flexion, in response to applied varus and valgus loads. METHODS: Twenty fresh-frozen cadaver knees were affixed to a six degree of freedom robotic arm with a universal force-moment sensor, and loaded with a 4Nm moment in varus and valgus at 0, 15, 30, 45, and 90 degrees of knee flexion. The resulting tibiofemoral angulation, displacement, and rotation were recorded. RESULTS: For each parameter investigated, the knee joint demonstrated more laxity at higher flexion angles. Varus angulation increased progressively from zero (2.0 degrees varus) to 90 (5.2 degrees varus) degrees of knee flexion (p<0.001). Valgus angulation also increased progressively, from zero (1.5 degrees valgus) to 90 (3.9 degrees valgus) degrees of knee flexion (p<0.001). At all flexion angles, the magnitude of tibiofemoral angle deviation was larger with varus than with valgus loading (p<0.05). CONCLUSIONS: We conclude that the native knee exhibits small increases in coronal plane laxity as the flexion angle increases, and that the knee has generally more laxity under varus load than with valgus load throughout the Range of Motion (ROM). Larger differences in laxity of more than 2 to 3 degrees , or peak laxity specifically during the range of mid-flexion, were not found in our cadaver model and are not likely to represent normal coronal plane kinematics. LEVEL OF EVIDENCE: Level V, biomechanical cadaveric study. PMID- 26875049 TI - Monthly swelling of the knee - Case report and review of the literature. AB - INTRODUCTION: We report a 17-year old with monthly swelling of her knee. The complaints are associated with the menstrual cycle. After physical examination, radiographs, MRI and an arthroscopy with biopsies, a diagnosis of intra-articular endometriosis and menstrual arthritis was made. DISCUSSION: Both an intra articular manifestation of endometriosis and menstrual arthritis are very rare diagnoses. Extraperitoneal lesions of endometriosis are rare and the mechanism for spreading outside the retroperitoneal space is unknown. A similar situation exists for menstrual arthritis, it is thought that cytokines, which are produced as a reaction to retrograde menstruation, are the trigger for menstrual arthritis. A review of literature is given. CONCLUSION: A monthly recurrent, painful swelling of a joint, can and should give rise to thorough investigation. Differential diagnostic one should think of intra-articular manifestation of endometriosis and menstrual arthritis. We give a proposal for treatment. PMID- 26875051 TI - Range of movement correlates with the Oxford knee score after total knee replacement: A prediction model and validation. AB - BACKGROUND: Patient reported outcome measures are widely used in the evaluation of outcomes after Total Knee Replacement (TKR) in joint registries and large studies. The aim of this study was to assess the relationship between the Oxford knee score (OKS) and range of motion (ROM) after TKR, and to construct and validate prediction models of ROM from the measured OKS. METHODS: Eight hundred sixty patients reviewed five years postoperatively and 273 patients reviewed nine to 10 years postoperatively completed an OKS. Of these, 808 (94%) and 226 (83%) patients, respectively, had a complete dataset (knee extension and ROM) and formed the study cohort. RESULTS: Regression analysis demonstrated a significant correlation between the OKS and ROM (r=0.38, p<0.001) after adjusting for other confounding variables (age, sex, body mass index, and knee extension). A prediction model was constructed and validated using a second cohort of 226 patients at nine to 10 years after their TKR. Intraclass correlation demonstrated good reliability (r=0.60, 95% CI 0.47 to 0.69) between predicted and actual measured ROM for this group. However, when the OKS is used in isolation the reliability of the predicted ROM is diminished (intraclass correlation r=0.41, 95% CI 0.24 to 0.55). CONCLUSIONS: The OKS is an independent predictor of ROM after TKR. It is also possible to predict ROM from the OKS, but the reliability of this is improved when other independent predictors such as age, gender, body mass index (BMI) and degree of knee extension are also acknowledged. PMID- 26875050 TI - Early evolving joint degeneration by cartilage trauma is primarily mechanically controlled. AB - BACKGROUND: Mechanical and inflammatory processes add to osteoarthritis (OA). To what extent both processes contribute during the onset of OA after a cartilage trauma is unknown. This study evaluates whether local cartilage damage leads to focally confined or more generalized cartilage damage with synovial inflammation in the early development of joint tissue degeneration. METHODS: In nine goats, cartilage damage was surgically induced on the weight bearing area of exclusively the medial femoral condyle of the right knee joint. The other tibio-femoral compartments, lateral femoral condyle and lateral medial tibial plateau, were left untouched. The contralateral left knee joint of each animal served as an intra-animal control. Twenty weeks post-surgery changes in cartilage matrix integrity in each of the four compartments, medial and lateral synovial tissue inflammation, and synovial fluid IL-1beta and TNFalpha were evaluated. RESULTS: In the experimental medial femoral plateau, significant macroscopic, histologic, and biochemical cartilage damage was observed versus the contralateral control compartments. Also the articulating cartilage of the experimental medial tibial plateau was significantly more damaged. Whereas, no differences were seen between the lateral compartments of experimental and contralateral control joints. Synovial tissue inflammation was mild and only macroscopically (not histologically) significantly increased in the experimental medial compartments. Synovial fluid IL-1beta level was not different between experimental and contralateral control joints, and TNFalpha was overall beneath the detection limit. CONCLUSIONS: Local cartilage damage is a trigger for development of OA, which in early onset seems primarily mechanically driven. Early treatment of traumatic cartilage damage should take this mechanical component into consideration. PMID- 26875053 TI - Extension deficit after ACL reconstruction: Is open posterior release a safe and efficient procedure? AB - BACKGROUND: Extension loss is a potentially devastating consequence of anterior cruciate ligament reconstruction (ACLR). It can often be treated by anterior arthroscopic release. In rare cases, a chronic flexion contracture requires an additional posterior open release. To our knowledge, no study analysing the results of both posteromedial and posterolateral approaches has been performed so far. The purposes of this study were (1) to analyse the midterm outcome and complications of a combined procedure, anterior arthroscopic debridement and posterior open capsulotomy - for the treatment of chronic extension deficits after ACLR and (2) to describe the surgical technique of posterior open release with both posteromedial and posterolateral approaches. MATERIAL AND METHODS: This is a retrospective clinical cohort study. Twelve patients presenting a chronic flexion contracture of 10 degrees or more after ACLR treated by open posterior arthrolysis with an average follow-up time of 38months (range six to 90) were included. At last follow-up, they underwent both a clinical examination with range of motion analysis, International Knee Documentation Committee (IKDC) and KOOS scores. RESULTS: At follow-up, all patients except one (93%) achieved complete extension. Only one patient (7%) had a residual post-operative flexion deformity of five degrees. The range of motion (ROM) improved significantly after arthrolysis from 96 degrees +/-14.3 degrees (SD) to 14.3 degrees +/-7 degrees (SD)(p<0.001). No post-operative complications were recorded. No patients required further open debridement. The post-operative objective IKDC score was grade A for five patients, B for seven versus C for five patients and D for seven preoperatively. The mean post-operative subjective IKDC score was 86.4+/-9.7. The post-operative Knee injury and Osteoarthritis Outcome Score (KOOS) distribution was as follows: pain 93.8+/-5 (SD); symptoms 88+/-8.6 (SD); ADL 96.8+/-3.7 (SD); sports activities 83.6+/-12.3 (SD); and quality of life 82.9+/-8.8 (SD). Mean patients' satisfaction was 9.25+/-0.6 (SD) out of 10 after arthrolysis. CONCLUSIONS: Open posterior release with both posteromedial and posterolateral approaches is a safe and efficient additional procedure in case of persistent flexion contracture after ACLR with good ROM gain, functional scores and patients' satisfaction. LEVEL OF EVIDENCE: Therapeutic study - Level IV. PMID- 26875054 TI - Spontaneous Right Atrial Dissection Resulting in Tricuspid Regurgitation. PMID- 26875052 TI - Percutaneous freezing of sensory nerves prior to total knee arthroplasty. AB - BACKGROUND: Total knee arthroplasty (TKA) is a common procedure resulting in significant post-operative pain. Percutaneous cryoneurolysis targeting the infrapatellar branch of the saphenous nerve and anterior femoral cutaneous nerve could relieve post-operative knee pain by temporarily blocking sensory nerve conduction. METHODS: A retrospective chart review of 100 patients who underwent TKA was conducted to assess the value of adding perioperative cryoneurolysis to a multimodal pain management program. The treatment group consisted of the first 50 patients consecutively treated after the practice introduced perioperative (five days prior to surgery) cryoneurolysis as part of its standard pain management protocol. The control group consisted of the 50 patients treated before cryoneurolysis was introduced. Outcomes included hospital length of stay (LOS), post-operative opioid requirements, and patient-reported outcomes of pain and function. RESULTS: A significantly lower proportion of patients in the treatment group had a LOS of >=2days compared with the control group (6% vs. 67%, p<0.0001) and required 45% less opioids during the first 12weeks after surgery. The treatment group reported a statistically significant reduction in symptoms at the six- and 12-week follow-up compared with the control group and within-group significant reductions in pain intensity and pain interference at two- and six week follow-up, respectively. CONCLUSIONS: Perioperative cryoneurolysis in combination with multimodal pain management may significantly improve outcomes in patients undergoing TKA. Promising results from this preliminary retrospective study warrant further investigation of this novel treatment in prospective, randomized trials. LEVEL OF EVIDENCE: III. PMID- 26875055 TI - Leadless Pacemaker After Complicated Hematoma. PMID- 26875057 TI - Educational innovations in clinical pharmacogenomics. AB - Genetic and genomic discovery is revolutionizing medicine at an extraordinary pace, leading to a better understanding of disease and improved treatments for patients. This advanced pace of discovery presents an urgency to expand medical school curricula to include genetic and genomic testing (including pharmacogenomics), and integration of genomic medicine into clinical practice. Consequently, organizations and healthcare authorities have charged medical schools with training future physicians to be competent in their knowledge of genomic implementation. PMID- 26875058 TI - TRAPID or Trapped? PMID- 26875059 TI - Bedside Washout of a Septic Shoulder in the Emergency Department: A Case Report. AB - We present a case of successful bedside irrigation of a septic joint in the emergency department. Complicating factors prevented the patient from undergoing operative management. With a simple 2 catheter technique the authors irrigated the patient's septic shoulder at the bedside. The patient's pain and range of motion improved immediately following the technique. The patient had complete recovery without open drainage. With further investigation, definitive management of septic joints could begin in the emergency department. PMID- 26875056 TI - Beneficial Microbes Affect Endogenous Mechanisms Controlling Root Development. AB - Plants have incredible developmental plasticity, enabling them to respond to a wide range of environmental conditions. Among these conditions is the presence of plant growth-promoting rhizobacteria (PGPR) in the soil. Recent studies show that PGPR affect Arabidopsis thaliana root growth and development by modulating cell division and differentiation in the primary root and influencing lateral root development. These effects lead to dramatic changes in root system architecture that significantly impact aboveground plant growth. Thus, PGPR may promote shoot growth via their effect on root developmental programs. This review focuses on contextualizing root developmental changes elicited by PGPR in light of our understanding of plant-microbe interactions and root developmental biology. PMID- 26875060 TI - Use of Out-of-Hospital Ethanol Administration to Improve Outcome in Mass Methanol Outbreaks. AB - STUDY OBJECTIVE: Methanol poisoning outbreaks are a global public health issue, with delayed treatment causing poor outcomes. Out-of-hospital ethanol administration may improve outcome, but the difficulty of conducting research in outbreaks has meant that its effects have never been assessed. We study the effect of out-of-hospital ethanol in patients treated during a methanol outbreak in the Czech Republic between 2012 and 2014. METHODS: This was an observational case-series study of 100 hospitalized patients with confirmed methanol poisoning. Out-of-hospital ethanol as a "first aid antidote" was administered by paramedic or medical staff before the confirmation of diagnosis to 30 patients; 70 patients did not receive out-of-hospital ethanol from the staff (12 patients self administered ethanol shortly before presentation). RESULTS: The state of consciousness at first contact with paramedic or medical staff, delay to admission, and serum methanol concentration were similar among groups. The median serum ethanol level on admission in the patients with out-of-hospital administration by paramedic or medical staff was 84.3 mg/dL (interquartile range 32.7 to 129.5 mg/dL). No patients with positive serum ethanol level on admission died compared with 21 with negative serum ethanol level (0% versus 36.2%). Patients receiving out-of-hospital ethanol survived without visual and central nervous system sequelae more often than those not receiving it (90.5% versus 19.0%). A positive association was present between out-of-hospital ethanol administration by paramedic or medical staff, serum ethanol concentration on admission, and both total survival and survival without sequelae of poisoning. CONCLUSION: We found a positive association between out-of-hospital ethanol administration and improved clinical outcome. During mass methanol outbreaks, conscious adults with suspected poisoning should be considered for administration of out-of-hospital ethanol to reduce morbidity and mortality. PMID- 26875061 TI - Emergency Department Prescription Opioids as an Initial Exposure Preceding Addiction. AB - STUDY OBJECTIVE: Opioid abuse and overdose constitute an ongoing health emergency. Many presume opioids have little potential for iatrogenic addiction when used as directed, particularly in short courses, as is typical of the emergency department (ED) setting. We preliminarily explore the possibility that initial exposure to opioids by EDs could be related to subsequent opioid misuse. METHODS: This cross-sectional study surveyed a convenience sample of patients reporting heroin or nonmedical opioid use at an urban, academic ED. We estimated the proportion whose initial exposure to opioids was a legitimate medical prescription and the proportion of those prescriptions that came from an ED. Secondary measurements included the proportion of patients receiving nonopioid substances before initial opioid exposure, the source of opioids between initial exposure and onset of regular nonmedical use, and time from initial prescription to opioid use disorder. RESULTS: Of 59 subjects, 35 (59%; 95% confidence interval [CI] 47% to 71%) reported they were first exposed to opioids by a legitimate medical prescription, and for 10 of 35 (29%; 95% CI 16% to 45%), the prescription came from an ED. Most medically exposed subjects (28/35; 80%; 95% CI 65% to 91%) reported nonopioid substance use or treatment for nonopioid substance use disorders preceding the initial opioid exposure. Emergency providers were a source of opioids between exposure and onset of regular nonmedical use in 11 of 35 cases (31%; 95% CI 18% to 48%). Thirty-one of the 35 medically exposed subjects reported the time of onset of nonmedical use; median time from exposure to onset of nonmedical use was 6 months for use to get high (N=25; interquartile range [IQR] 2 to 36), 12 months for regular use to get high (N=24; IQR 2 to 36), 18 months for use to avoid withdrawal (N=26; IQR 2 to 38), and 24 months for regular use to avoid withdrawal (N=27; IQR 2 to 48). Eleven subjects (36%; 95% CI 21% to 53%) began nonmedical use within 2 months, and 9 of 11 (82%; 95% CI 53% to 96%) reported nonopioid substance use or treatment for alcohol abuse before initial opioid exposure. CONCLUSION: Although short-term opioid administration by emergency providers is unlikely to cause addiction by itself, ED opioid prescriptions may contribute to the development of addiction in some patients. There is an urgent need for further research to estimate long-term risks of short course opioid therapy so that the risk of iatrogenic addiction can be appropriately balanced with the benefit of analgesia. PMID- 26875062 TI - An Evaluation of Emergency Medicine Core Content Covered by Free Open Access Medical Education Resources. AB - STUDY OBJECTIVE: Emergency physicians are using free open access medical education (FOAM) resources at an increasing rate. The extent to which FOAM resources cover the breadth of emergency medicine core content is unknown. We hypothesize that the content of FOAM resources does not provide comprehensive or balanced coverage of the scope of knowledge necessary for emergency medicine providers. Our objective is to quantify emergency medicine core content covered by FOAM resources and identify the predominant FOAM topics. METHODS: This is an institutional review board-approved, retrospective review of all English-language FOAM posts between July 1, 2013, and June 30, 2014, as aggregated on http://FOAMem.com. The topics of FOAM posts were compared with those of the emergency medicine core content, as defined by the American Board of Emergency Medicine's Model of the Clinical Practice of Emergency Medicine (MCPEM). Each FOAM post could cover more than 1 topic. Repeated posts and summaries were excluded. RESULTS: Review of the MCPEM yielded 915 total emergency medicine topics grouped into 20 sections. Review of 6,424 FOAM posts yielded 7,279 total topics and 654 unique topics, representing 71.5% coverage of the 915 topics outlined by the MCPEM. The procedures section was covered most often, representing 2,285 (31.4%) FOAM topics. The 4 sections with the least coverage were cutaneous disorders, hematologic disorders, nontraumatic musculoskeletal disorders, and obstetric and gynecologic disorders, each representing 0.6% of FOAM topics. Airway techniques; ECG interpretation; research, evidence-based medicine, and interpretation of the literature; resuscitation; and ultrasonography were the most overrepresented subsections, equaling 1,674 (23.0%) FOAM topics when combined. CONCLUSION: The data suggest an imbalanced and incomplete coverage of emergency medicine core content in FOAM. The study is limited by its retrospective design and use of a single referral Web site to obtain available FOAM resources. More comprehensive and balanced coverage of emergency medicine core content is needed if FOAM is to serve as a primary educational resource. PMID- 26875063 TI - Same Physician, Different Location, Different Patient Satisfaction Scores. AB - STUDY OBJECTIVE: We assess whether patient satisfaction scores differ for individual emergency physicians according to the clinical setting in which patients are treated. METHODS: We obtained Press Ganey satisfaction survey results from June 2013 to August 2014 for patients treated in either an urban hospital emergency department (ED) or 2 affiliated suburban urgent care centers. The same physicians work in all 3 facilities. Physicians with available survey results from at least 10 patients in both settings were included. Survey scores range from 1 (very poor) to 5 (very good). Survey questions directly assessed physicians' courtesy, ability to keep patients informed about their treatment, concern for patient comfort, listening ability, and the overall care at the facility. We calculated differences in mean urgent care and ED scores for individual physicians, along with the mean of these differences. Our primary outcome was the mean difference between urgent care and ED score with respect to physician courtesy. RESULTS: Seventeen physicians met inclusion criteria. For all 17 physicians, the point estimate for the mean urgent care courtesy score was higher than the point estimate for the mean ED courtesy score. The mean difference in courtesy scores between urgent care and the ED was 0.35 (95% confidence interval 0.22 to 0.49). ED scores were also consistently lower than urgent care scores for keeping patients informed about their treatment, concern for patient comfort, listening ability, and overall care rating. CONCLUSION: Although these results are limited by small sample size, we found that physicians consistently received lower satisfaction ratings from ED patients than from urgent care patients. This challenges the validity of using satisfaction scores to compare providers in different practice settings. PMID- 26875064 TI - Is it time for treat to target strategy in osteoporosis? PMID- 26875065 TI - Proper site of corticosteroid injection for the treatment of idiopathic frozen shoulder: Results from a randomized trial. AB - OBJECTIVE: The objective is to determine whether corticosteroid injection into the subacromial space was not inferior to intra-articular injection in patients with idiopathic frozen shoulder (FS), and whether combined injections had an additive effect. METHODS: Patients with idiopathic FS (n=126) were randomly assigned to receive ultrasound-guided intra-articular (IA group), subacromial (SA group), or combined IA and subacromial injections (IA+SA group). All groups received a total dose of 40mg triamcinolone acetonide. The outcome measures included the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeon (ASES) shoulder score, subjective shoulder value (SSV), and passive range of motion before and at 3, 6, and 12 weeks after treatment. RESULTS: There was significant effect of time on all measurements such that all measures improved in all groups (P<0.001) during the 12 weeks after treatment. Group-by-time interactions were significant for ASES (P=0.006), VAS (P<0.001), SSV (P=0.03), and internal rotation (P=0.014). Between-group comparisons revealed a significant improvement in the IA (P<0.001) and IA+SA (P<0.001) groups as compared to the SA group. The IA+SA group demonstrated significant improvement in internal rotation as compared to the IA group (P=0.046). CONCLUSION: The efficacy of corticosteroid injection into the SA space in idiopathic FS was inferior to IA injection up to 12 weeks; however, combination injections had an additive effect on increasing the internal rotation angle. These results indicate that although the glenohumeral joint is a major site in the pathogenesis of idiopathic FS, the SA space may be a contributing site. PMID- 26875066 TI - TNFalpha antagonist therapy in axial spondyloarthritis: Can we do better? PMID- 26875067 TI - School-based exposure to hazardous air pollutants and grade point average: A multi-level study. AB - The problem of environmental health hazards around schools is serious but it has been neglected by researchers and analysts. This is concerning because children are highly susceptible to the effects of chemical hazards. Some ecological studies have demonstrated that higher school-level pollution is associated with lower aggregate school-level standardized test scores likely, related to increased respiratory illnesses and/or impaired cognitive development. However, an important question remains unexamined: How do school-level exposures impact individual children's academic performance? To address this, we obtained socio demographic and grades data from the parents of 1888 fourth and fifth grade children in the El Paso (Texas, USA) Independent School District in 2012. El Paso is located on the US-side of the Mexican border and has a majority Mexican-origin population. School-based hazardous air pollution (HAP) exposure was calculated using census block-level US Environmental Protection Agency National Air Toxics Assessment risk estimates for respiratory and diesel particulate matter (PM). School-level demographics were obtained from the school district. Multi-level models adjusting for individual-level covariates (e.g., age, sex, race/ethnicity, English proficiency, and economic deprivation) and school-level covariates (e.g., percent of students economically disadvantaged and student-teacher ratio) showed that higher school-level HAPs were associated with lower individual-level grade point averages. An interquartile range increase in school-level HAP exposure was associated with an adjusted 0.11-0.40 point decrease in individual students' grade point averages (GPAs), depending on HAP type and emission source. Respiratory risk from HAPs had a larger effect on GPA than did diesel PM risk. Non-road mobile and total respiratory risk had the largest effects on children's GPA of all HAP variables studied and only mother's level of education had a larger effect than those two variables on children's GPA. The five school-level demographic indicators were only weakly associated with GPA. The study findings indicate the need for regulations on school siting and adjacent land uses to protect children's environmental health. PMID- 26875068 TI - Parasaccharibacter apium, gen. nov., sp. nov., Improves Honey Bee (Hymenoptera: Apidae) Resistance to Nosema. AB - The honey bee, Apis mellifera L., is host to a variety of microorganisms. The bacterial community that occupies the adult worker gut contains a core group of approximately seven taxa, while the hive environment contains its own distribution of bacteria that is in many ways distinct from the gut. Parasaccharibacter apium, gen. nov., sp. nov., is a hive bacterium found in food stores and in larvae, worker jelly, worker hypopharyngeal glands, and queens. Parasaccharibacter apium increases larval survival under laboratory conditions. To determine if this benefit is extended to colonies in the field, we tested if P. apium 1) survives and reproduces in supplemental pollen patty, 2) is distributed throughout the hive when added to pollen patty, 3) benefits colony health, and 4) increases the ability of bees to resist Nosema. Parasaccharibacter apium survived in supplemental diet and was readily consumed by bees. It was distributed throughout the hive under field conditions, moving from the pollen patty to hive larvae. While P. apium did not significantly increase colony brood production, food stores, or foraging rates, it did increase resistance to Nosema infection. Our data suggest that P. apium may positively impact honey bee health. PMID- 26875069 TI - Risk rtPA: An iOS mobile application based on TURN for predicting 90-day outcome after IV thrombolysis. AB - OBJECTIVE: We recently developed Thrombolysis risk Using mRS and NIHSS (TURN), a simple score using only prestroke mRS scores and admission NIHSS scores to predict 90-day outcome after IV thrombolysis in ischemic stroke patients. Our purpose was to develop and test a mobile application for utilization of TURN at the bedside. METHODS: We developed Risk rtPA, an iOS mobile application based on TURN for prediction of 90-day excellent and severe outcome after IV thrombolysis. Excellent outcome was defined as 90-day mRS<=1. Severe outcome was defined as 90 day mRS>=5. Predictors for excellent and severe outcome were calculated using the inverse logit of -TURN and TURN respectively. We retrospectively validated our mobile application using data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Sensitivity and specificity analyses were performed using receiver operating characteristic (ROC) curves. RESULTS: Prediction of excellent and severe outcome using Risk rtPA followed an S-shaped curve as expected. We confirmed this finding using data from the NINDS trial. Cutoffs selected after ROC analysis predicted severe outcome with sensitivity of 94.4% and specificity of 52.2%, and excellent outcome with specificity of 83.9% and sensitivity of 61.2%. CONCLUSION: The Risk rtPA mobile application predicted 90-day excellent and severe outcome in most clinically relevant cases. This mobile application brings the TURN score to the bedside for prediction of 90-day outcome in ischemic stroke patients being evaluated for IV thrombolysis. PMID- 26875070 TI - Molecular Staging of Sentinel Lymph Nodes Identifies Melanoma Patients at Increased Risk of Nodal Recurrence. AB - BACKGROUND: Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND). STUDY DESIGN: In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison. RESULTS: A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044). CONCLUSIONS: Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study. PMID- 26875071 TI - Robotic-Assisted Transperitoneal Pelvic Lymphadenectomy for Metastatic Melanoma: Early Outcomes Compared with Open Pelvic Lymphadenectomy. AB - BACKGROUND: In the absence of iliac or obturator nodal involvement, the role of pelvic lymphadenectomy (PLND) for melanoma is controversial, but for select patients, long-term survival can be achieved with the combination of superficial inguinal (inguinofemoral) and PLND. Open PLND (oPLND) is often limited in visual exposure and can be associated with considerable postoperative pain. Robotic PLND (rPLND) is a minimally invasive technique that provides excellent visualization of the iliac and obturator nodes. Outcomes comparing the open and robotic techniques have not been reported previously for patients with melanoma. STUDY DESIGN: We reviewed our experience with rPLND for melanoma and compared clinical and pathologic results with oPLND. We evaluated operative times, nodal yield, and short-term oncologic outcomes. RESULTS: Thirteen rPLND (2013 to 2015) (15 attempted, 87% success rate) and 25 oPLND (2010 to 2015) consecutive cases were completed. Pelvic lymphadenectomy was combined with an open inguinofemoral dissection in 8 of 13 (62%) robotic and 17 of 25 (68%) open cases. Median length of stay was shorter in the rPLND group, with 1.0 vs 3.5 days for pelvic-only cases (p < 0.001) and 2.5 vs 4.0 days (p < 0.001) for combined ilioinguinal cases. Median operative time (227 vs 230 minutes; p = 0.96) and nodal yield (11 vs 10 nodes; p = 0.53) were not different between rPLND and oPLND. CONCLUSIONS: Robotic PLND offers a safe, effective, minimally invasive approach to resect the pelvic lymph nodes in patients with melanoma, with no significant difference in nodal yield or operative times, but a shorter length of stay compared with oPLND. PMID- 26875073 TI - Erratum to: Cluster categorization of urban roads to optimize their noise monitoring. PMID- 26875072 TI - Fine mapping of barley locus Rps6 conferring resistance to wheat stripe rust. AB - KEY MESSAGE: Barley resistance to wheat stripe rust has remained effective for a long time and, therefore, the genes underlying this resistance can be a valuable tool to engineer durable resistance in wheat. Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a major disease of wheat that is causing large economic losses in many wheat-growing regions of the world. Deployment of Pst resistance genes has been an effective strategy for controlling this pathogen, but many of these genes have been defeated by new Pst races. In contrast, genes providing resistance to this wheat pathogen in other grass species (nonhost resistance) have been more durable. Barley varieties (Hordeum vulgare ssp. vulgare) are predominately immune to wheat Pst, but we identified three accessions of wild barley (Hordeum vulgare ssp. spontaneum) that are susceptible to Pst. Using these accessions, we mapped a barley locus conferring resistance to Pst on the distal region of chromosome arm 7HL and designated it as Rps6. The detection of the same locus in the cultivated barley 'Tamalpais' and in the Chinese barley 'Y12' by an allelism test suggests that Rps6 may be a frequent component of barley intermediate host resistance to Pst. Using a high-density mapping population (>10,000 gametes) we precisely mapped Rps6 within a 0.14 cM region (~500 kb contig) that is colinear to regions in Brachypodium (<94 kb) and rice (<9 kb). Since no strong candidate gene was identified in these colinear regions, a dedicated positional cloning effort in barley will be required to identify Rps6. The identification of this and other barley genes conferring resistance to Pst can contribute to our understanding of the mechanisms for durable resistance against this devastating wheat pathogen. PMID- 26875074 TI - New method for quantification of dye sorption using SBA mesoporous silica as a target sorbent. AB - In this work, a new method for the quantification of methyl violet cationic dye sorption onto SBA-15 mesoporous silica was developed. This method related the intensity of coloration of SBA-15 samples (after reached equilibrium sorption) within dye concentration in aqueous solution using Image-Pro Plus software. The sorption process of methyl violet dye onto SBA-15 was analyzed varying different initial parameters (dye concentration, mass of sorbent, pH of dye solution, and contact sorption time). SBA-15 proved as efficient sorbent for removal of methyl violet dye in contact time of 5 min, with maximum percentage of dye removal 99% at pH 8. The results obtained from Image-Pro Plus showed to be in good agreement with the sorption parameters obtained by UV/Vis spectroscopy, which has been the most commonly used instrument for quantification of dye sorption. The image analysis method proved well prediction of dye concentrations with maximum relative error of 1.83%. The advantages of this method are low cost and reliable quantitative evaluation with minimum of time. PMID- 26875075 TI - Soil quality index as affected by different cropping systems in northwestern Himalayas. AB - Soil quality assessment provides a tool for evaluating the sustainability of soils under different crop cafeterias. Our objective was to develop the soil quality index for evaluating the soil quality indicators under different cropping systems in northwest Himalaya-India. Composite soil samples were taken from the study area from different cropping systems which include T1 (forest soil control), T2 (rice-oilseed, lower belts), T3 (rice-oilseed, higher belts), T4 (rice-oats), T5 (rice-fallow), T6 (maize-oats), T7 (maize-peas), T8 (apple), T9 (apple-beans), and T10 (apple-maize). Physical, chemical, and biological soil indicators were determined, and it was found that soil enzyme activities involved in nutrient cycling were significantly higher in forest soils, which were reflected in higher levels of available pool of nutrients. Carbon stocks were found significantly higher in forest soil which was translated in improved soil physical condition. Principal component analysis (PCA) was performed to reduce multidimensionality of data followed by scoring by homothetic transformation of the selected indicators. Pearson's interclass correlation was performed to avoid redundancy, and highly correlated variables were not retained. Inclusion of legumes in the apple orchard floor recorded highest soil quality rating across the treatments. Cereal-based cropping systems were found in lower soil quality rating; however, the incorporation of peas in the system improved soil health. PMID- 26875076 TI - Distance between intramuscular nerve and artery in the extraocular muscles: a preliminary immunohistochemical study using elderly human cadavers. AB - PURPOSE: Extraocular muscles are quite different from skeletal muscles in muscle fiber type and nerve supply; the small motor unit may be the most well known. As the first step to understanding the nerve-artery relationship, in this study we measured the distance from the arteriole (25-50 MUm in thickness) to the nerve terminal twigs in extraocular muscles. MATERIALS AND METHODS: With the aid of immunohistochemistry for nerves and arteries, we examined the arteriole-nerve distance at 10-15 sites in each of 68 extraocular muscles obtained from ten elderly cadavers. The oblique sections were nearly tangential to the muscle plate and included both global and orbital aspects of the muscle. RESULTS: In all muscles, the nerve twigs usually took a course parallel to muscle fibers, in contrast to most arterioles that crossed muscles. Possibly due to polyinnervation, an intramuscular nerve plexus was evident in four rectus and two oblique muscles. The arteriole-nerve distance usually ranged from 300 to 400 MUm. However, individual differences were more than two times greater in each of seven muscles. Moreover, in each muscle the difference between sites sometimes reached 1 mm or more. The distance was generally shorter in the rectus and oblique muscles than in the levator palpebrae muscle, which reached statistical significance (p < 0.05). CONCLUSIONS: The differences in arteriole-nerve distances between sites within each muscle, between muscles, and between individuals might lead to an individual biological rhythm of fatigue in oculomotor performance. PMID- 26875077 TI - Muscle attachment to the condylar process of mandible: anatomical considerations. PMID- 26875078 TI - Improvement of a Privacy Authentication Scheme Based on Cloud for Medical Environment. AB - Medical systems allow patients to receive care at different hospitals. However, this entails considerable inconvenience through the need to transport patients and their medical records between hospitals. The development of Telecare Medicine Information Systems (TMIS) makes it easier for patients to seek medical treatment and to store and access medical records. However, medical data stored in TMIS is not encrypted, leaving patients' private data vulnerable to external leaks. In 2014, scholars proposed a new cloud-based medical information model and authentication scheme which would not only allow patients to remotely access medical services but also protects patient privacy. However, this scheme still fails to provide patient anonymity and message authentication. Furthermore, this scheme only stores patient medical data, without allowing patients to directly access medical advice. Therefore, we propose a new authentication scheme, which provides anonymity, unlinkability, and message authentication, and allows patients to directly and remotely consult with doctors. In addition, our proposed scheme is more efficient in terms of computation cost. The proposed system was implemented in Android system to demonstrate its workability. PMID- 26875079 TI - Assessment of the usability and impact of the Idaho Health Data Exchange (IHDE). AB - Eighty four health care professionals participated in an online survey assessing the usability, and clinical and administrative impact of the Idaho Health Data Exchange's (IHDE) Virtual Health Record (VHR). The IHDE VHR allows authorized users to use a secure web interface to view lab, radiology and transcribed reports from multiple facilities and view medical histories on patients in the data exchange. Results indicate the usability of the IHDE VHR was almost universally positively rated with the Software Usability Measurement Inventory (SUMI) utilized as the assessment method. Medical providers however had the lowest rating of the exchange, raising concerns about the need for additional training and support. The addition of other Idaho health care organizations to the health data exchange was most widely desired, with the most frequently cited benefit being more comprehensive access to patients' records. In contrast to other published evaluations of health data exchanges in the U.S., few of the concerns emerged about cost of implementation of the data exchange or trust in the quality of information contained therein. PMID- 26875080 TI - Advances of Molecular Targeted Therapy in Gastric Cancer. AB - BACKGROUND: Gastric cancer is the second most common cause of cancer-related death in the world, and its prognosis remains poor with a median overall survival of 12 months for advanced disease. Advances in the understanding of molecular genetics have led to the development of directed molecular targeted therapy in gastric cancer, leading to improve patient outcomes and quality of life. DISCUSSION: In the treatment of human epidermal growth factor receptor 2 (HER2) positive gastric cancer, the addition of trastuzumab significantly improves survival in the first-line setting of therapy. Ramucirumab, an antibody directed against vascular endothelial growth factor receptor 2, significantly improved progression-free and overall survival and has been approved for second-line treatment of gastric cancer. Anti-mesenchymal-epithelial transition (c-MET), mammalian target of rapamycin inhibitors, and polo-like kinase 1 inhibitors are under investigation as a novel therapeutic option for the treatment of gastric cancer. The novel therapies target the key immune checkpoint interaction between a T cell co-inhibitory receptor called programmed death 1 (PD-1) and one of its immunosuppressive ligands, PD-L1. This article reviews molecular targeted therapies in gastric cancer, in light of recent advances. PMID- 26875082 TI - [Ecology of Glossina palpalis VANDERPLANK, 1949 (Diptera: Glossinidae) in mangrove area of Guinea: influence of tides on tsetse densities]. AB - The mangrove area on the Guinea littoral constitutes a favourable habitat for transmission of Trypanosoma brucei gambiens, the parasite causing sleeping sickness also called Human African Trypanosmosis (HAT), due the simultaneous presence of the vector (tsetse flies) and the human hosts. In order to assess the influence of the sea tides on the densities of Glossina palpalis gambiensis (Gpg), major vector of HAT in the mangrove, entomological surveys were performed using two transects, according to tides coefficient (great and small) and tide daily fluctuations (high and low). On each transect, 12 biconical traps were deployed through the mangrove to the continent. In total, up to 612 Gpg were caught, giving a density of 2.13 flies/trap/day (f/t/d). Highest captures were recorded during small tides and more tsetse were caught during the dry season than in the wet season. There were significant differences between captures when considering the different biotopes, and highest tsetse densities were recorded at the junction of the river and the channel of the mangrove (6.17+/-5.24); and in the channels of mangrove (3.50+/-3.76), during high tides of small coefficients. The results of this study may be used to improve vector control methods. PMID- 26875081 TI - Liposarcoma of Hypopharynx and Esophagus: a Unique Entity? AB - PURPOSE: Liposarcoma is the most common soft tissue sarcoma in adults. It represents approximately 20 % of all mesenchymal malignancies. It most frequently involves retroperitoneum, trunk, and extremities. Hypopharyngeal and esophageal localization of liposarcoma is extremely rare. METHODS: We performed a systematic review of literature and reported 26 and 33 cases of hypopharyngeal and esophageal liposarcoma. We analyzed natural history, imaging features, histology, treatment, and prognosis, with a specific focus to similarities and differences between tumors of hypopharynx and esophagus. RESULTS: Hypopharyngeal and esophageal liposarcomas have more similarities than differences. Incidence has a peak at 6th and 7th decades. The diagnostic procedures are barium swallow, endoscopic examination, and CT/MR imaging. Well-differentiated liposarcoma represents the most frequent histological subtype. Surgical excision is the main treatment. Endoscopic resection can be useful for pedunculated tumors of hypopharynx and cervical esophagus. Differences between hypopharyngeal and esophageal liposarcoma are represented by local recurrence rate (greater for hypopharyngeal tumors), number of giant tumors, and time to recurrence (greater for esophageal tumors). Finally, liposarcomas of distal esophagus need more extended approaches. CONCLUSIONS: Liposarcomas of hypopharynx and cervical esophagus could be considered a unique pathological entity, with similar features and treatment options. Survival rate is dependent on histological type and location. Local recurrence is common, especially for hypopharyngeal liposarcoma, while the risk of lymph node or distant metastasis is very low. Patients should undergo regular examinations to rule out local recurrence, also for a long time, especially for esophageal tumors. PMID- 26875083 TI - Facilitating triple rhomboid flaps for meningomyelocele defect closure using a honeycomb structure as a template. AB - PURPOSE: Various reconstruction options are available for the soft-tissue coverage of meningomyelocele defects. For small defects, primary closure or local single flaps may be sufficient, while large defects require more complex reconstructive techniques. This study suggests an easy way for surgeons to close large meningomyelocele defects using triple rhomboid flaps. METHODS: The hexagonal structure of a honeycomb was considered when planning for the coverage of large meningomyelocele defects. The intact skin around the defect was imagined as multiple hexagons, which allowed us to plan triple rhomboid flaps correctly and more easily. This technique was used in seven patients with defects ranging from 7 * 5 to 12 * 8 cm in size. RESULTS: No major postoperative complications were seen. Minimal dehiscence was observed in two patients and healed secondarily. CONCLUSIONS: The honeycomb modification for planning triple rhomboid flaps is an easy, practical, and memorable approach for surgeons reconstructing large meningomyelocele defects. PMID- 26875084 TI - A morphometric analysis of the mandibular canal by cone beam computed tomography and its relevance to the sagittal split ramus osteotomy. AB - PURPOSE: The aim of the present study was to morphometrically analyze the mandibular canal through the mandibular ramus by cone beam computed tomography (CBCT) and to relate the findings to performing sagittal split ramus osteotomy. METHODS: CBCT of 200 patients were analyzed. Five parameters were measured at the axial scan, from the mandibular foramen to 21 mm below it (3-mm intervals). The canal was classified according to the position within the bone marrow space. Variations were evaluated according to age, sex, side, and number of mandibular teeth. RESULTS/CONCLUSIONS: The following measurements increased gradually towards the most inferior level of measurement: the total thickness of the mandibular ramus through the center of the mandibular canal, the width of the bone marrow space (both buccal and lingual), and the narrowest width from the mandibular canal inner cortical to the mandibular ramus external cortical. The inner diameter of the mandibular canal slightly decreased to the same direction. Concerning the mandibular canal position within the bone marrow space, the percentage of the separate type increased towards the most inferior level of measurement, and the contact and fusion types decreased. Age, number of teeth, and sex had no significant influence on the total thickness of the mandibular ramus and on the narrowest width from the mandibular canal inner cortical to the mandibular ramus external cortical. PMID- 26875085 TI - Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies. AB - INTRODUCTION: One of the common malignant tumors of the head and neck worldwide with generally unfavorable prognosis is squamous cell carcinoma (OSCC) of the oral cavity. Early detection of primary, secondary, or recurrent OSCC by liquid biopsy tools is much needed. CASE PRESENTATION: Twelve blood biomarkers were used for monitoring a case of OSCC suffering from precancerous oral lichen ruber planus mucosae (OLP). After curative R0 tumor resection of primary OSCC (buccal mucosa), elevated epitope detection in monocytes (EDIM)-Apo10, EDIM-transketolase like-1 (TKTL1), squamous cell carcinoma antigen (SCC-Ag), total serum lactate dehydrogenase (LDH), and its anaerobic isoforms (LDH-4, LDH-5) decreased to normal levels. Three and six months after surgery, transformation of suspicious mucosal lesions has been accompanied with an increase of EDIM scores, total serum LDH values, and a metabolic shift from aerobic (decrease of LDH-1, LDH-2) to anaerobic (increase of LDH-4, LDH-5) conditions. Two months later, secondary OSCC was histopathologically analyzed after tissue biopsy. Cytokeratin fraction 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19 9) were not affected during the clinical course of carcinogenesis. CONCLUSIONS: A combination strategy using a standardized panel of established (metabolic) blood biomarkers (TKTL1, LDH, LDH isoenzymes) is worth and can be recommended among others (apoptosis resistance-related Apo10, SCC-Ag) for early detection and diagnosis of primary, secondary, and recurrent OSCC. A tandem strategy utilizing (metabolic pronounced) routine liquid biopsies with imaging techniques may enhance diagnosis of OSCC in the future. Although we demonstrated the diagnostic utility of separated liquid biopsies in our previous study cohorts, further investigations in a larger patient cohort are necessary to recommend this combination strategy (EDIM blood test, LDH value, metabolic shift of LDH isoenzymes, and others, e.g., SCC-Ag or immunophenotyping) as a diagnostic tool for the addition to the OSCC staging system and as a routine procedure in the aftercare. PMID- 26875087 TI - Inhibition of Tumor Necrosis Factor-alpha and Interleukin-1beta Production in Lipopolysaccharide-Stimulated Monocytes by Methanolic Extract of Elephantopus scaber Linn and Identification of Bioactive Components. AB - The methanolic extract of E. scaber Linn was evaluated for anti-inflammatory activity by determining its effects on production of pro-inflammatory cytokines like Tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta) in Lipopolysaccharide (LPS) stimulated monocytes. The cytotoxicity of the extract was analyzed prior to the cytokine quantification assays. The extract was further subjected to UPLC MS Q-TOF, for the identification of bioactive components present in the crude extract. The extract was found not to be cytotoxic against monocytes, and exhibited significant inhibition in the production of pro inflammatory cytokines. The presence of 34 components in the methanolic extract was detected through mass spectrum analysis. PMID- 26875086 TI - Optimization of Biomass and 5-Aminolevulinic Acid Production by Rhodobacter sphaeroides ATCC17023 via Response Surface Methodology. AB - Microbial 5-aminolevulinic acid (ALA) produced from wastewater is considered as potential renewable energy. However, many hurdles are needed to be overcome such as the regulation of key influencing factors on ALA yield. Biomass and ALA production by Rhodobacter sphaeroides was optimized using response surface methodology. The culturing medium was artificial volatile fatty acids wastewater. Three additives were optimized, namely succinate and glycine that are precursors of ALA biosynthesis, and D-glucose that is an inhibitor of ALA dehydratase. The optimal conditions were achieved by analyzing the response surface plots. Statistical analysis showed that succinate at 8.56 mmol/L, glycine at 5.06 mmol/L, and D-glucose at 7.82 mmol/L were the best conditions. Under these optimal conditions, the highest biomass production and ALA yield of 3.55 g/L and 5.49 mg/g-biomass were achieved. Subsequent verification experiments at optimal values had the maximum biomass production of 3.41 +/- 0.002 g/L and ALA yield of 5.78 +/- 0.08 mg/g-biomass. PMID- 26875088 TI - Hinged external fixation for Regan-Morrey type I and II fractures and fracture dislocations. AB - Elbow fracture-dislocation is always demanding to manage due to the considerable soft-tissue swelling or damage involved, which can make an early open approach and ligamentous reconstruction impossible. The purpose of this study was to evaluate the role of elbow hinged external fixation (HEF) as a definitive treatment in patients with elbow dislocations associated with Regan-Morrey (R-M) type I and II coronoid fractures and soft-tissue damage. We treated 11 patients between 2010 and 2012 with HEF. Instability tests and standard X-ray examinations were performed before surgery and 1-3 to 3-6 months after surgery, respectively. All patients underwent a preoperative CT scan. Outcomes were assessed with a functional assessment scale (Mayo Elbow Performance Score, MEPS) that included 4 parameters: pain, ROM, stability, and function. The results were good or excellent in all 11 patients, and no patient complained of residual instability. Radiographic examination showed bone metaplasia involving the anterior and medial sides of the joint in 5 patients. HEF presented several advantages: it improves elbow stability and it avoids long and demanding surgery in particular in cases with large soft tissue damage. We therefore consider elbow HEF to be a viable option for treating R-M type I and II fracture-dislocations. PMID- 26875089 TI - If it can be done, it should be done,...or not? PMID- 26875090 TI - Co-expression of chimeric chitinase and a polygalacturonase-inhibiting protein in transgenic canola (Brassica napus) confers enhanced resistance to Sclerotinia sclerotiorum. AB - OBJECTIVES: Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum is one of the major fungal diseases of canola. To develop resistance against this fungal disease, the chit42 from Trichoderma atroviride with chitin-binding domain and polygalacturonase-inhibiting protein 2 (PG1P2) of Phaseolus vulgaris were co expressed in canola via Agrobacterium-mediated transformation. RESULTS: Stable integration and expression of transgenes in T0 and T2 plants was confirmed by PCR, Southern blot and RT-PCR analyses. Chitinase activity and PGIP2 inhibition were detected by colorimetric and agarose diffusion assay in transgenic lines but not in untransformed plants. The crude proteins from single copy transformant leaves having high chitinase and PGIP2 activity (T16, T8 and T3), showed up to 44 % inhibition of S. sclerotiorum hyphal growth. The homozygous T2 plants, showing inheritance in Mendelian fashion (3:1), were further evaluated under greenhouse conditions for resistance to S. sclerotiorum. Intact plants contaminated with mycelia showed resistance through delayed onset of the disease and restricted size and expansion of lesions as compared to wild type plants. CONCLUSIONS: Combined expression of chimeric chit42 and pgip2 in Brassica napus L. provide subsequent protection against SSR disease and can be helpful in increasing the canola production in Iran. PMID- 26875091 TI - Phylogenetic classification of Aureobasidium pullulans strains for production of feruloyl esterase. AB - OBJECTIVE: The objective was to phylogenetically classify diverse strains of Aureobasidium pullulans and determine their production of feruloyl esterase. RESULTS: Seventeen strains from the A. pullulans literature were phylogenetically classified. Phenotypic traits of color variation and endo-beta-1,4-xylanase overproduction were associated with phylogenetic clade 10 and particularly clade 8. Literature strains used for pullulan production all belonged to clade 7. These strains and 36 previously classified strains were tested for feruloyl esterase production, which was found to be associated with phylogenetic clades 4, 11, and particularly clade 8. Clade 8 strains NRRL 58552 and NRRL 62041 produced the highest levels of feruloyl esterase among strains tested. CONCLUSIONS: Production of both xylanase and feruloyl esterase are associated with A. pullulans strains in phylogenetic clade 8, which is thus a promising source of enzymes with potential biotechnological applications. PMID- 26875092 TI - Purification and characteristics of a novel bacteriocin produced by Enterococcus faecalis L11 isolated from Chinese traditional fermented cucumber. AB - OBJECTIVE: To purify and characterize a novel bacteriocin with broad inhibitory spectrum produced by an isolate of Enterococcus faecalis from Chinese fermented cucumber. RESULTS: E. faecalis L11 produced a bacteriocin with antimicrobial activity against both Escherichia coli and Staphylococcus aureus. The amino acid sequence of the purified bacteriocin, enterocin L11, was assayed by Edman degradation method. It differs from other class II bacteriocins and exhibited a broad antimicrobial activity against not only Gram-positive bacteria, including Bacillus subtilis, S. aureus, Listeria monocytogenes, Sarcina flava, Lactobacillus acidophilus, L. plantarum, L. delbrueckii subsp. delbrueckii, L. delbrueckii subsp. bulgaricus and Streptococcus thermophilus, but also some Gram negative bacteria including Salmonella typhimurium, E. coli and Shigella flexneri. Enterocin L11 retained 91 % of its activity after holding at 121 degrees C for 30 min. It was also resistant to acids and alkalis. CONCLUSIONS: Enterocin L11 is a novel broad-spectrum Class II bacteriocin produced by E. faecalis L11, and may have potential as a food biopreservative. PMID- 26875093 TI - COMP-Ang1 promotes long-term survival of allogeneic islet grafts in a bioinert perforated chamber by inhibiting inflammation via inhibition of the TLR4 signaling pathway. AB - OBJECTIVES: To evaluate the effects of cartilage oligomeric matrix protein (COMP) angiopoietin-1 (Ang1) on allogeneic islet graft survival in a bioinert perforated chamber. RESULTS: COMP-Ang1 treatment significantly decreased lipopolysaccharide-induced cell apoptosis and islet-related lymph node cell proliferation (both P < 0.01). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 levels in the chamber exudate were significantly lower in the COMP-Ang1 + chamber group than in the chamber group (all P < 0.05), as were the protein expression levels. COMP-Ang1 significantly inhibited the expression of Toll-like receptor 4 (TLR4) in cultured islets. Finally, full COMP-Ang1 treatment resulted in the longest survival time among the treatment groups. CONCLUSION: Combined use of the bioinert perforated chamber with COMP-Ang1 is an effective strategy for improving islet allograft survival. PMID- 26875094 TI - Quantifying the legacy of the Chinese Neolithic on the maternal genetic heritage of Taiwan and Island Southeast Asia. AB - There has been a long-standing debate concerning the extent to which the spread of Neolithic ceramics and Malay-Polynesian languages in Island Southeast Asia (ISEA) were coupled to an agriculturally driven demic dispersal out of Taiwan 4000 years ago (4 ka). We previously addressed this question using founder analysis of mitochondrial DNA (mtDNA) control-region sequences to identify major lineage clusters most likely to have dispersed from Taiwan into ISEA, proposing that the dispersal had a relatively minor impact on the extant genetic structure of ISEA, and that the role of agriculture in the expansion of the Austronesian languages was therefore likely to have been correspondingly minor. Here we test these conclusions by sequencing whole mtDNAs from across Taiwan and ISEA, using their higher chronological precision to resolve the overall proportion that participated in the "out-of-Taiwan" mid-Holocene dispersal as opposed to earlier, postglacial expansions in the Early Holocene. We show that, in total, about 20% of mtDNA lineages in the modern ISEA pool result from the "out-of-Taiwan" dispersal, with most of the remainder signifying earlier processes, mainly due to sea-level rises after the Last Glacial Maximum. Notably, we show that every one of these founder clusters previously entered Taiwan from China, 6-7 ka, where rice-farming originated, and remained distinct from the indigenous Taiwanese population until after the subsequent dispersal into ISEA. PMID- 26875096 TI - Bone and Celiac Disease. AB - More than 50% of untreated patients with celiac disease (CD) have bone loss detected by bone densitometry (dual-energy X-ray absorptiometry:DXA). Moreover, patients with CD are more likely to have osteoporosis and fragility fractures, especially of the distal radius. Although still controversial, we recommend DXA screening in all celiac disease patients, particularly in those with symptomatic CD at diagnosis and in those who present risk factors for fracture such as older age, menopausal status, previous fracture history, and familial hip fracture history. Bone microarchitecture, especially the trabecular network, may be deteriorated, explaining the higher fracture risk in these patients. Adequate calcium and vitamin D supplementation are also recommended to optimize bone recovery, especially during the first years of gluten free diet (GFD). If higher fracture risk persists after 1 or 2 years of GFD, specific osteoactive treatment may be necessary to improve bone health. PMID- 26875095 TI - Adaptive evolution of interleukin-3 (IL3), a gene associated with brain volume variation in general human populations. AB - Greatly expanded brain volume is one of the most characteristic traits that distinguish humans from other primates. Recent studies have revealed genes responsible for the dramatically enlarged human brain size (i.e., the microcephaly genes), and it has been well documented that many microcephaly genes have undergone accelerated evolution along the human lineage. In addition to being far larger than other primates, human brain volume is also highly variable in general populations. However, the genetic basis underlying human brain volume variation remains elusive and it is not known whether genes regulating human brain volume variation also have experienced positive selection. We have previously shown that genetic variants (near the IL3 gene) on 5q33 were significantly associated with brain volume in Chinese population. Here, we provide further evidence that support the significant association of genetic variants on 5q33 with brain volume. Bioinformatic analyses suggested that rs31480 is likely to be the causal variant among the studied SNPs. Molecular evolutionary analyses suggested that IL3 might have undergone positive selection in primates and humans. Neutrality tests further revealed signatures of positive selection of IL3 in Han Chinese and Europeans. Finally, extended haplotype homozygosity (EHH) and relative EHH analyses showed that the C allele of SNP rs31480 might have experienced recent positive selection in Han Chinese. Our results suggest that IL3 is an important genetic regulator for human brain volume variation and implied that IL3 might have experienced weak or modest positive selection in the evolutionary history of humans, which may be due to its contribution to human brain volume. PMID- 26875097 TI - Weekend working: a retrospective cohort study of maternal and neonatal outcomes in a large NHS delivery unit. AB - OBJECTIVES: Mandatory weekend working for NHS consultants is currently the subject of intense political debate. The Secretary of State for Health's proposed 7-day contract policy is based on the claim that such working patterns will improve patient outcomes. We evaluate this claim by taking advantage of as-if-at random presentation of women for non-elective deliveries throughout the week. We examine (i) whether consultants currently perform fewer deliveries during weekends versus weekdays, and (ii) whether adverse outcomes increase during weekends. STUDY DESIGN: We conducted a retrospective cohort study using data on all non-elective deliveries from January 2008 to December 2013 in a large UK obstetrics centre (n=27,466). We used Pearson's chi-squared tests to make direct comparisons of adverse outcome rates during weekdays versus weekends. Outcomes included: estimated maternal blood loss >=1.5l; severe perineal trauma; delayed neonatal respiration; umbilical arterial pH <7.1; and critical incidents at delivery. RESULTS: Consultants currently perform the same proportion of non elective deliveries on weekends and weekdays (2.3% versus 2.6%, p=0.25). We found no increase in any adverse maternal or neonatal outcomes during weekends versus weekdays, despite high statistical power to detect such differences. Moreover, adverse outcomes are no higher during periods of the weekend when consultants are not routinely present compared to equivalent periods during weekdays. CONCLUSIONS: Under current working arrangements, women who would benefit from consultant-led delivery are equally likely to receive one on weekends compared to weekdays. Weekend delivery has no effect on maternal or neonatal morbidity. Adopting mandatory 7-day contracts is unlikely to make any difference to either consultant-led delivery during weekends or to patient outcomes. PMID- 26875098 TI - Prospective assessment of clinical symptoms associated with enterovirus and parechovirus genotypes in a multicenter study in Dutch children. AB - BACKGROUND: Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. OBJECTIVES: To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. STUDY DESIGN: This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. RESULTS: Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p=0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p=0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p<0.001). CONCLUSIONS: EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection. PMID- 26875099 TI - Relative sensitivity of immunohistochemistry, multiple reaction monitoring mass spectrometry, in situ hybridization and PCR to detect Coxsackievirus B1 in A549 cells. AB - BACKGROUND: Enteroviruses (EVs) have been linked to the pathogenesis of several diseases and there is a collective need to develop improved methods for the detection of these viruses in tissue samples. OBJECTIVES: This study evaluates the relative sensitivity of immunohistochemistry (IHC), proteomics, in situ hybridization (ISH) and RT-PCR to detect one common EV, Coxsackievirus B1 (CVB1), in acutely infected human A549 cells in vitro. STUDY DESIGN: A549 cells were infected with CVB1 and diluted with uninfected A549 cells to produce a limited dilution series in which the proportion of infected cells ranged from 10(-1) to 10(-8). Analyses were carried out by several laboratories using IHC with different anti-EV antibodies, ISH with both ViewRNA and RNAScope systems, liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM/MS/MS), and two modifications of RT-PCR. RESULTS: RT-PCR was the most sensitive method for EV detection yielding positive signals in the most diluted sample (10(-8)). LC/MRM/MS/MS detected viral peptides at dilutions as high as 10(-7). The sensitivity of IHC depended on the antibody used, and the most sensitive antibody (Dako clone 5D8/1) detected virus proteins at a dilution of 10(-6), while ISH detected the virus at dilutions of 10(-4). CONCLUSIONS: All methods were able to detect CVB1 in infected A549 cells. RT-PCR was most sensitive followed by LC/MRM/MS/MS and then IHC. The results from this in vitro survey suggest that all methods are suitable tools for EV detection but that their differential sensitivities need to be considered when interpreting the results from such studies. PMID- 26875100 TI - Impact of the Great East Japan Earthquake on feeding methods and newborn growth at 1 month postpartum: results from the Fukushima Health Management Survey. AB - This study examined the effects of three disasters (the Great East Japan Earthquake of March 11, 2011, followed by a tsunami and the Fukushima Daiichi Nuclear Power Plant accident) on feeding methods and growth in infants born after the disasters. Using results from the Fukushima Health Management Survey, Soso District (the affected area where the damaged nuclear power plant is located) and Aizu District (a less-affected area located farthest from the plant) were compared. In this study, newborn and maternal background characteristics were examined, as well as feeding methods, and other factors for newborn growth at the first postpartum examination for 1706 newborns born after the disaster in the affected (n = 836) and less-affected (n = 870) areas. Postpartum examinations took place 1 month after birth. Feeding method trends were examined, and multivariate regression analyses were used to investigate effects on newborn mass gain. There were no significant differences in background characteristics among newborns in these areas. When birth dates were divided into four periods to assess trends, no significant change in the exclusive breastfeeding rate was found, while the exclusive formula-feeding rate was significantly different across time periods in the affected area (p = 0.02). Multivariate analyses revealed no significant independent associations of maternal depression and change in medical facilities (possible disaster effects) with other newborn growth factors in either area. No area differences in newborn growth at the first postpartum examination or in exclusive breastfeeding rates were found during any period. Exclusive formula-feeding rates varied across time periods in the affected, but not in the less-affected area. It is concluded that effective guidance to promote breast-feeding and prevent exclusive use of formula is important for women in post-disaster circumstances. PMID- 26875101 TI - Factors Influencing the Frequency of Emergency Department Utilization by Individuals with Substance Use Disorders. AB - This study assessed the characteristics of individuals with substance use disorders (ISUDs) according to their frequency of emergency department (ED) utilization, and examined which variables were associated with an increase in ED visits using Andersen's model. Data linkage of administrative databanks from three sources [addiction rehabilitation centre registry, physician billing systems, and hospital discharge databank] for 4526 ISUDs was performed. Predisposing, enabling and need factors associated with number of ED visits were determined using a negative binomial regression model and generalised estimating equations. The rate of ED utilization for this population was 9.6 %. Increased number of ED visits was associated with the following variables: older age, social fragmentation, number of consultations with general practitioners, number of consultations with psychiatrists, number of consultations with other types of physicians, alcohol abuse, drug abuse, schizophrenia, anxiety disorders, personality disorders, co-occurring substance dependence and mental disorders, co occurring substance dependence and chronic physical disorders, and co-occurring mental health disorders and chronic physical disorders. By contrast, a diagnosis of substance dependence, co-occurring drug and alcohol abuse, and a co-occurring diagnosis of substance dependence with mental health and chronic physical disorders decreased ED visits. Efforts to reduce avoidable use of EDs should focus on chronic-disease management and other related strategies aimed at reinforcing services to ISUDs in the community, especially for ISUDs with a co occurring diagnosis of either mental health disorders or chronic physical disorders. PMID- 26875102 TI - Influencing Factors on Choosing Psychiatry as a Career: An Exploration in Chinese University Students. AB - There is a consistent need of psychiatric professionals in the world including China, and a consistent challenge to recruit more medical students into the psychiatric careers. We aimed to look for factors which have an impact on career choosing of psychiatry in Chinese university students. We invited 508 non-medical students (NM), 304 medical students without (MO) and 123 medical students with clinical internship experience (MW), to answer a matrix of 43 questions regarding factors influencing career-choosing of psychiatry. Answers to these questions were analyzed through exploratory and confirmatory factor analyses, once the latent factors were identified and structurally-validated, their mean scores in three groups of students were calculated. Five factors with five items each were identified, namely social status inferiority, career importance, practice reward, career preference, and practice stress. NM scored lower than MO and MW did on Social Status Inferiority; NM group scored higher than MO and MW groups did on Career Importance; MW scored lower than NM and MO did on Practice Reward and on Career Preference; Regarding Practice Stress, NM scored higher than MO did, who then in turn, scored higher than MW did. In addition, Practice Stress was positively correlated with advice of the medical educators; and Social Status Inferiority and Career Preference were positively correlated with the psychiatry teaching of the medical educators. Raising career rewards, improving social status, and reinforcing psychiatric education might help to recruit more medical students to specialize in psychiatry practicing. PMID- 26875103 TI - The Relationship Between Gender, Posttraumatic Stress Disorder from Past Trauma, Alexithymia and Psychiatric Co-morbidity in Chinese Adolescents: A Moderated Mediational Analysis. AB - This study focused on a group of Chinese adolescents and examined whether the degree of alexithymia would mediate the effect of PTSD from past trauma onto psychiatric co-morbidities and whether gender differences would moderate the mediational effects of alexithymia. Three hundred and twenty-six adolescents were recruited from two schools and completed the Posttraumatic Stress Diagnostic Scale, General Health Questionnaire-28 and Toronto Alexithymia Scale-20. The results showed that 54 % had no trauma in their lives; 10, 21 and 15 % met the criteria for full, partial and no-PTSD respectively. After adjusting the number of traumatic events, difficulty identifying feelings mediated the path between PTSD from past trauma and psychiatric co-morbidity. Gender moderated the mediational effect of difficulty identifying feelings. To conclude, adolescents can develop PTSD symptoms and psychiatric co-morbidity following exposure to a traumatic event. For both males and females, difficulty getting in touch with feelings can influence the impact of PTSD onto psychiatric co-morbidity. PMID- 26875104 TI - A Study of the Impact of Cannabis on Doses of Discharge Antipsychotic Medication in Individuals with Schizophrenia or Schizoaffective Disorder. AB - Patients with schizophrenia or schizoaffective disorder have a high prevalence of comorbid cannabis use disorder (CUD). CUD has been associated with poorer outcomes in patients. We compared doses of antipsychotic medications at the time of discharge from hospital among inpatients with schizophrenia or schizoaffective disorder with or without concurrent cannabis use. We reviewed the medical records of patients (N = 8157) with schizophrenia or schizoaffective disorder discharged from the hospital between 2008 and 2012. The patients were divided into two groups; those with urine drug tests positive for cannabis and those negative for cannabis. Doses of antipsychotic medications were converted to chlorpromazine equivalents. Bivariate analyses were done with Student's t test for continuous variables and chi 2 test for categorical variables. Linear regression was carried out to adjust for potential confounders. Unadjusted analysis revealed that the cannabis positive group was discharged on lower doses of antipsychotic medication compared with the cannabis negative group (geometric mean chlorpromazine equivalent doses 431.22 +/- 2.20 vs 485.18 +/- 2.21; P < 0.001). However, the difference in geometric mean chlorpromazine equivalent doses between the two groups was no longer significant after adjusting for sex, age, race, and length of stay (geometric mean difference 0.99; 95 % CI 0.92-1.10). Though limited by lack of information on duration, amount and severity of cannabis use, as well as inability to control for other non-antipsychotic medications, our study suggests that cannabis use did not significantly impact on doses of antipsychotics required during the periods of acute exacerbation in patients with schizophrenia or schizoaffective disorder. PMID- 26875105 TI - The Impact of Integrating Crisis Teams into Community Mental Health Services on Emergency Department and Inpatient Demand. AB - This investigation focused on the impact of integrating crisis team members into community mental health services on emergency department and adult mental health inpatient unit demand within an Australian public health service. Mixed methods were used including (a) the comparison of service use data with that of two other comparable services (both of which had community-based crisis teams), (b) surveys of (i) patients and carers and (ii) staff, and (c) focus groups with staff. The numbers of emergency department presentations with mental health conditions and adult mental health inpatient separations increased 13.9 and 5.7 %, respectively, from FY2006/07 to FY2012/13. Between the three services, there were minimal differences in the percentages of presentations with mental health conditions, the distribution of mental health presentations across a 24-h period, and the triage categories assigned to these patients. Survey participants reported that patients used the emergency department due to the urgency of situations, perceptions that gaining access to mental health services would take less time, and the unavailability of mental health services when help is needed. Staff identified several issues (e.g. inappropriate referrals) that may be unnecessary in increasing emergency department demand. The integration of crisis team members into community mental health services does not seem to have produced an increase in emergency department admissions or inpatient separations beyond what might be expected from population growth. The potential may exist, however, to reduce emergency department admissions through addressing the issue of inappropriate referrals. PMID- 26875106 TI - Comparison of Objective and Subjective Life Balance Between Women With and Without a Personality Disorder. AB - Life balance is associated to health, well-being and quality of life and is a target of psychiatric rehabilitation interventions. However, little is known about this life dimension in women living with personality disorders. The purpose of this descriptive-correlational study was to compare and explore relationships between subjective life balance, objective time use, quality of life and perceived stress in women without a mental health disorder (n = 43) and women with a personality disorder (clusters B and C) (n = 30), aged between 18 and 50 years old. The variables were measured with the Life Balance Inventory (subjective life balance), the Occupational Questionnaire (objective time use), the Depression Anxiety Stress Scale (perceived stress) and the Quality of Life Index (satisfaction and importance with life domains). The analyses showed that women with a personality disorder spend significantly less time in work but more time in daily tasks and leisure. Subjective life balance, quality of life and perceived stress were significantly lower in women with a personality disorder (p < 0.05). In women with a personality disorder, subjective life balance was explained by quality of life (R2 = 27.5 %). In women without a mental illness, subjective life balance was explained by quality of life and motherhood (R2 = 36.1 %). To support the recovery of women with personality disorders and their quality of life, it is important to address objective and subjective time use to enable accomplishment of a variety of meaningful activities. PMID- 26875108 TI - Lesion guided stereotactic radiofrequency thermocoagulation for palliative, in selected cases curative epilepsy surgery. AB - INTRODUCTION: Resective epilepsy surgery is an established treatment option in patients with pharmacoresistant, lesion related epilepsy. Yet, if the presurgical work-up proves multi-focal organization of the epileptogenic zone, or the area of intended resection is close to eloquent brain areas, patients may decide against resections because of an unfavorable risk-benefit-ratio. We assess if lesion guided cortical stereotactic radiofrequency thermocoagulation (L-RFTC) is a potential surgical alternative in these patients. METHODS: We performed seven procedures of L-RFTC. Three patients had monofocal epilepsy arising close to eloquent structures; in four, invasive pre-surgical workup documented monofocal seizure onset but strong interictal epileptic activity also independent and distant from the seizure onset zone. L-RFTC was restricted to the lesional area (=seizure onset site). RESULTS: 12 to 37 months after RFTC worthwhile seizure improvement was achieved in 6 patients. One patient became seizure free following complete coagulation of a focal cortical dysplasia, two had had 1-2 auras under tapered but not under continued medication. In one patient only subclinical seizures persisted. In one patient hypermotor seizures were transformed into milder short tonic seizures and another one had a seizure reduction by 50%. Only one patient did not profit at all. One patient developed a persisting neurological deficit. SIGNIFICANCE: In patients with complex epileptogenic zones L-RFTC can lead to worthwhile seizure reduction. This qualifies this procedure as a palliative surgical technique with potential good risk-benefit ratio. In patients with small focal cortical dysplasias L-RFTC may even allow minimal invasive surgery with curative intention. PMID- 26875109 TI - Genetics of reflex seizures and epilepsies in humans and animals. AB - INTRODUCTION: Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies. METHODS: References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies. RESULTS: Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in patients with symptomatic epilepsies but have also been reported in the setting chromosomal disorders or genetically inherited lysosomal storage diseases. DISCUSSION: The genetic background of reflex seizures and epilepsies is heterogeneous and mostly unknown with no major gene identified in humans. The benefits offered by next generation sequencing technologies should be merged with increasing information on animal models that represent an useful tool to study the mechanism underlying epileptogenesis. Finally, we expect that genetic studies will lead to a better understanding of the multiple factors involved in the pathophysiology of reflex seizures, and eventually to develop preventive strategies focused on seizure control and therapy optimization. PMID- 26875107 TI - Effects of parent and child behaviours on overweight and obesity in infants and young children from disadvantaged backgrounds: systematic review with narrative synthesis. AB - BACKGROUND: Despite the crucial need to develop targeted and effective approaches for obesity prevention in children most at risk, the pathways explaining socioeconomic disparity in children's obesity prevalence remain poorly understood. METHODS: We conducted a systematic review of the literature that investigated causes of weight gain in children aged 0-5 years from socioeconomically disadvantaged or Indigenous backgrounds residing in OECD countries. Major electronic databases were searched from inception until December 2015. Key words identified studies addressing relationships between parenting, child eating, child physical activity or sedentary behaviour and child weight in disadvantaged samples. RESULTS: A total of 32 articles met the inclusion criteria. The Mixed Methods Appraisal Tool quality rating for the studies ranged from 25 % (weak) to 100 % (strong). Studies predominantly reported on relationships between parenting and child weight (n = 21), or parenting and child eating (n = 12), with fewer (n = 8) investigating child eating and weight. Most evidence was from socio-economically disadvantaged ethnic minority groups in the USA. Clustering of diet, weight and feeding behaviours by socioeconomic indicators and ethnicity precluded identification of independent effects of each of these risk factors. CONCLUSIONS: This review has highlighted significant gaps in our mechanistic understanding of the relative importance of different aspects of parent and child behaviours in disadvantaged population groups. PMID- 26875110 TI - Stabbing simulations and DNA transfer. AB - Technical developments have made it possible to analyze very low amounts of DNA. This has many advantages, but the drawback of this technological progress is that interpretation of the results becomes increasingly complex: the number of mixed DNA profiles increased relatively to single source DNA profiles and stochastic effects in the DNA profile, such as drop-in and drop-out, are more frequently observed. Moreover, the relevance of low template DNA material regarding the activities alleged is not as straightforward as it was a few years ago, when for example large quantities of blood were recovered. The possibility of secondary and tertiary transfer is now becoming an issue. The purpose of this research is twofold: first, to study the transfer of DNA from the handler and secondly, to observe if handlers would transfer DNA from persons closely connected to them. We chose to mimic cases where the offender would attack a person with a knife. As a first approach, we envisaged that the defense would not give an alternative explanation for the origin of the DNA. In our transfer experiments (4 donors, 16 experiments each, 64 traces), 3% of the traces were single DNA profiles. Most of the time, the DNA profile of the person handling the knife was present as the major profile: in 83% of the traces the major contributor profile corresponded to the stabber's DNA profile (in single stains and mixtures). Mixture with no clear major/minor fraction (12%) were observed. 5% of the traces were considered of insufficient quality (more than 3 contributors, presence of a few minor peaks). In that case, we considered that the stabber's DNA was absent. In our experiments, no traces allowed excluding the stabber, however it must be noted that precautions were taken to minimize background DNA as knives were cleaned before the experiments. DNA profiles of the stabber's colleagues were not observed. We hope that this study will allow for a better understanding of the transfer mechanism and of how to assess and describe results given activity level propositions. In this preliminary research, we have focused on the transfer of DNA on the hand of the person. Besides, more research is needed to assign the probability of the results given an alternative activity proposed by the defense, for instance when the source of the DNA is not contested, but that the activities are. PMID- 26875111 TI - Availability of Japanese Government's supplemental texts on radiation reflecting the Fukushima Daiichi Nuclear Power Plant accident for elementary and secondary education from dental students' understanding. AB - Following the Fukushima Nuclear Power Plant accident, the Japanese government created two supplemental texts about radiation reflecting the accident for elementary, middle school, and high school students. These texts were made to explain radiation and consequently to obtain public consent for the continuation of the nuclear program. The present study aimed to evaluate the appropriateness of the content of the texts and to collect the basic data on the level of understanding necessary to improve radiation education. Lectures on radiology including nuclear energy and the Fukushima accident were given to 44 fourth-year dental students in 2013. The questionnaire was administered in 2014 when these students were in their sixth-year. The survey was also administered to 40 first year students and 41 fourth-year students who hadn't any radiology lectures. Students rated their level of understanding of 50 phrases used in the texts on a four-point scale (understanding = 3, a little knowledge = 2, having heard = 1, no knowledge = 0). Questions on taking an advanced physics course in high school and means of learning about radiation in daily life were also asked. The level of understanding of phrases in the supplemental text for middle and high school students was significantly higher among sixth-year students (mean = 1.43) than among first-year (mean = 1.12) or fourth-year (mean = 0.93) students (p < 0.05). Overall, the level of understanding was low, with scores indicating that most students knew only a little. First-year students learning about radiation from television but four-year and six-year students learning about radiation from newspaper scored significantly higher (p < 0.05). It was concluded that radiation education should be improved by using visual material and preparing educators to teach the material for improving the public's understanding of radiation use especially nuclear power generation because the phrases used in the supplementary texts are very difficult for students to understand. PMID- 26875113 TI - Correlating behaviour and gene expression endpoints in the dopaminergic system after modafinil administration in mouse. AB - The mechanisms of action of modafinil continue to be poorly characterised and its potential for abuse in preclinical models remains controverted. The aim of this study was to further elucidate the mechanism of action of modafinil, through a potential behavioural and molecular association in the mouse. A conditioned place preference (CPP) paradigm was implemented to investigate the rewarding properties of modafinil. Whole genome expression and qRT-PCR analysis were performed on the ventral tegmental area (VTA), nucleus accumbens (NAC) and prefrontal cortex (PFC) of modafinil-treated and control animals. Modafinil administration (65 mg/kg) induced an increase in locomotor activity, an increase in the change of preference for the drug paired side after a conditioning period as well as changes to gene expression profiles in the VTA (120 genes), NAC (23 genes) and PFC (19 genes). A molecular signature consisting of twelve up-regulated genes was identified as common to the three brain regions. Multiple linear correlation analysis showed a strong correlation (R(2)>0.70) between the behavioural and molecular endpoints in the three brain regions. We show that modafinil had a concomitant effect on CPP, locomotor activity, and up-regulation of interferon gamma (IFN-gamma) regulated genes (Gbp2, Gbp3, Gbp10, Cd274, Igtp), while correlating the latter set of genes with behaviour changes evaluated through the CPP. A potential association can be proposed based on the dysregulation of p47 family genes and Gbp family of IFN-gamma induced GTPases. In conclusion, these findings suggest a link between the behavioural and molecular events in the context of modafinil administration. PMID- 26875112 TI - Is there a role of nab-paclitaxel in the treatment of advanced non-small cell lung cancer? The data suggest yes. AB - Nab-paclitaxel is a novel therapeutic agent, which was approved in combination with carboplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC) regardless of histologic subtype in the United States of America by the Food and Drug Administration in 2012 and by the European Commission in 2015. This approval was based on the results of a phase III clinical trial showing superior response rates compared with solvent-based paclitaxel in combination with carboplatin. This review will focus on the early development and clinical data to date supporting the use of nab-paclitaxel in advanced NSCLC. The clinical question central to this review is whether nab-paclitaxel has a place in the current therapeutic landscape of advanced NSCLC. PMID- 26875114 TI - Modulatory effect of the 5-HT1A agonist buspirone and the mixed non hallucinogenic 5-HT1A/2A agonist ergotamine on psilocybin-induced psychedelic experience. AB - The mixed serotonin (5-HT) 1A/2A/2B/2C/6/7 receptor agonist psilocybin dose dependently induces an altered state of consciousness (ASC) that is characterized by changes in sensory perception, mood, thought, and the sense of self. The psychological effects of psilocybin are primarily mediated by 5-HT2A receptor activation. However, accumulating evidence suggests that 5-HT1A or an interaction between 5-HT1A and 5-HT2A receptors may contribute to the overall effects of psilocybin. Therefore, we used a double-blind, counterbalanced, within-subject design to investigate the modulatory effects of the partial 5-HT1A agonist buspirone (20mg p.o.) and the non-hallucinogenic 5-HT2A/1A agonist ergotamine (3mg p.o.) on psilocybin-induced (170 ug/kg p.o.) psychological effects in two groups (n=19, n=17) of healthy human subjects. Psychological effects were assessed using the Altered State of Consciousness (5D-ASC) rating scale. Buspirone significantly reduced the 5D-ASC main scale score for Visionary Restructuralization (VR) (p<0.001), which was mostly driven by a reduction of the VR item cluster scores for elementary and complex visual hallucinations. Further, buspirone also reduced the main scale score for Oceanic Boundlessness (OB) including derealisation and depersonalisation phenomena at a trend level (p=0.062), whereas ergotamine did not show any effects on the psilocybin-induced 5D-ASC main scale scores. The present finding demonstrates that buspirone exerts inhibitory effects on psilocybin-induced effects, presumably via 5-HT1A receptor activation, an interaction between 5-HT1A and 5-HT2A receptors, or both. The data suggest that the modulation of 5-HT1A receptor activity may be a useful target in the treatment of visual hallucinations in different psychiatric and neurological diseases. PMID- 26875115 TI - Portraits of TET-mediated DNA hydroxymethylation in cancer. AB - The discovery of TET-mediated DNA hydroxymethylation as a mechanism of DNA demethylation, along with the observation of disrupted hydroxymethylation patterns in cancer, sparked high hopes of better understanding malignant processes. In this review, we discuss a plethora of recent studies that have shed light on the mechanisms and biological consequences of DNA hydroxymethylation pattern changes in various cancers. A picture is taking shape, in which TET proteins appear as both promoters and suppressors of cancer. Their impairment at multiple levels creates abnormal 5hmC landscapes that affect, often in concert with key cancer pathways, a wider range of biological processes than initially proposed. As the picture gains in scope and precision, the prospect of 5hmC pattern-targeting cancer therapies shimmers in the distance. PMID- 26875116 TI - Non-targeted chromatographic analyses of cuticular wax flavonoids from Physalis alkekengi L. AB - Since Chinese lantern (Physalis alkekengi L.) represents a rich source of various bioactive secondary metabolites, there is an urge for its detailed characterization. Non-polar flavonoid aglycones represent one of the few bioactive species found in plant's cuticular waxes. The separation of flavonoids is already extensively covered in the literature, but methods dedicated to separation and identification of methylated flavonoids are rather scarce. In the present study a non-targeted approach for the separation, isolation and identification of methylated flavonoids present in P. alkekengi L. var. franchetii cuticular waxes was established. A rapid and simple separation on HPTLC silica gel was developed for preliminary screening of flavonoids. Fast HPLC UV-MS(n) and HPLC-UV methods using a C6-Phenyl and a C18 stationary phase were also developed, respectively. In both cases, the right combination of temperature and tetrahydrofuran, as a mobile phase modifier, were shown to be crucial for a baseline separation of all studied compounds. By employing a semi-preparative analog of the C18 column, a simultaneous isolation of pure unknown analytes was achieved. Using these developed methods in combination with NMR, four 3-O methylated flavonols were detected and identified in P. alkekengi L. var. franchetii cuticular waxes: myricetin 3,7,3'-trimethyl ether, quercetin 3,7 dimethyl ether, myricetin 3,7,3',5'-tetramethyl ether and quercetin 3,7,3' trimethyl ether. Moreover, the simple and fast isocratic HPLC-UV-MS(n) method (under 8min) should prove useful in quality control of P. alkekengi L. var. franchetii by enabling chromatographic fingerprinting of external methylated flavonols. Finally, a rationale for the mechanism of separation of these metabolites by HPLC is also given, which establishes a foundation for future development of chromatographic methods for methylated flavonols and related compounds. PMID- 26875117 TI - Study of matrix effects for liquid chromatography-electrospray ionization tandem mass spectrometric analysis of 4 aminoglycosides residues in milk. AB - Matrix effect (ME) is always a major issue for the development of LC-MS/MS method. ME resulting from co-eluting residual matrix components can affect the ionization efficiency of target analytes, leading to quantification errors of the analytes of interest. The present work evaluates MEs of milk samples on simultaneous analysis of four aminoglycosides residues via LC-ESI/MS/MS including streptomycin, dihydrostreptomycin, spectinomycin and kanamycin. Approaches to reduce MEs were examined: optimization of the sample preparation, sample dilution and lower flow rate used. Three commercial sorbents were tested including Oasis MCX, Oasis HLB and Oasis WCX. WCX behaved better for all analytes, but high MEs (80.8-134.9%) were obtained. Therefore, a consecutive SPE of tC18-WCX was found to effectively reduce ME. Milk samples from different manufacturers were analyzed and low MEs (85.6-112.9%) were obtained. PMID- 26875118 TI - Self-assembled covalent capillary coating of diazoresin/carboxyl fullerene for analysis of proteins by capillary electrophoresis and a comparison with diazoresin/graphene oxide coating. AB - Self-assembled and covalently linked capillary coatings of carboxyl fullerenes (C60-COOH) were prepared using photosensitive diazoresin (DR) as a coupling agent. Layer by layer (LBL) self-assembled DR/C60-COOH coatings based on ionic bonding was fabricated first on the inner surface of silica capillary, and subsequently converted into covalent bonding after treatment with UV light through a unique photochemistry reaction of DR. The covalently bonded coatings had the ability of suppressing protein adsorption on the inner surface of silica capillary, and thus the baseline separation of lysozyme (Lys), cytochrome c (Cyt c), bovine serum albumin (BSA) and myoglobin (Mb) was achieved within 13min by using capillary electrophoresis (CE). The covalently linked DR/C60-COOH capillary coatings presented good chemical stability and repeatability. The reproducibility of the separation of proteins was less than 1%, 2.5%, and 3.5%, respectively, for run-to-run, day-to-day, capillary-to-capillary, respectively; and the RSD of migration time for the proteins are all less than 2.5% after a continuous 100 times running in a coating column. Compared with DR/graphene oxide (GO) coatings prepared by the same method, the DR/C60-COOH capillary coatings showed excellent protein separation performance due to a self-lubrication based anti-fouling mechanism. Because of the replacement of highly toxic and moisture sensitive silane coupling agent by DR in the covalent coating preparation, this method may provide an environmentally friendly and simple way to prepare the covalently coated capillaries for CE. PMID- 26875119 TI - Chiral separation by a terminal chirality triggered P-helical quinoline oligoamide foldamer. AB - A P-helical quinoline oligoamide foldamer was grafted on silica and applied as an HPLC stationary phase for chiral separation. The P-handedness of the quinoline oligoamide foldamer was induced by a (1S)-camphanyl group, which was introduced at the N-terminus of a tetrameric quinoline oligoamide foldamer (Cmp-Q4). To immobilize the foldamer on porous silica particles, a trimethoxysilyl group was introduced at the opposing end of the foldamer. Elemental analysis indicated that the amount of foldamer on the silica surface was 0.57MUmol/m(2). Circular dichroism and vibrational CD spectra of Cmp-Q4 and Cmp-Q4-immobilized silica (Sil Q4-Cmp) suggested that the helical structure of Cmp-Q4 was altered on the silica surface whilst retaining a chiral structure. The chiral recognition ability of Sil-Q4-Cmp was evaluated with various aromatic enantiomers. Sil-Q4-Cmp showed enantio-selectivity for axially chiral molecules (e.g., alphaTrigger's base=1.26 and alphaBinaphthol=1.07). Sil-Q4-Cmp showed remarkable recognition of helical octameric quinoline oligoamides with isobutoxy and triethylene glycol side chains (alpha=10.35 and 14.98, respectively). In contrast, an (1S)-camphanyl group immobilized porous silica showed no chiral recognition for any enantiomers tested in this study. To elucidate the chiral separation mechanism of Sil-Q4-Cmp, thermodynamic parameters were calculated using van't Hoff plots. HPLC results and thermodynamic parameters suggested that the chiral recognition of Sil-Q4-Cmp is based on the helical structure of Cmp-Q4 and other thermally dependent interactions such as hydrophobic effects associated with aromatic stacking. This work represents the first known application of aromatic foldamers in chiral separation. PMID- 26875120 TI - Separation of heavy metals from water by functionalized glycidyl methacrylate poly (high internal phase emulsions). AB - Removal of silver, lead and cadmium ions from both model solutions and real contaminated water was achieved, in a flow through manner, by using highly porous functionalized poly(glycidyl methacrylate) materials, prepared by the polymerisation of high internal phase emulsions (polyHIPE), with significant sorption differences between metals allowing for selective removal. PolyHIPEs, initially prepared from glycidyl methacrylate as a functional monomer, were functionalized with pentaerythritol tetrakis(3-mercaptopropionate), 1,9 nonanedithiol and 2-aminobenzenethiol via the epoxy ring opening on the polymer supports and applied in a flow-through manner via encasements into dedicated disk holders. Capacity of 21.7mg Ag per gram of polymer was found for 1,9 nonanedithiol functionalized polymers, while the capacity was decreasing with the decreasing ionic radius of the metal; the dynamics of sorption also depended on metal ion size and furthermore on the thiol used for the polymer functionalization. PMID- 26875122 TI - [What is new in the European Society of Cardiology 2015 Guidelines for the Diagnosis and Management of Pericardial Disease?]. PMID- 26875121 TI - Acylated-naproxen as the surface-active template in the preparation of micro- and nanospherical imprinted xerogels by emulsion techniques. AB - A strategy based on water-in-oil emulsion for the dispersion of a sol-gel mixture into small droplets was employed with the view of the production of naproxen imprinted micro- and nanospheres. The procedure, aiming at a surface imprinting process, comprised the synthesis of a naproxen-derived surfactant. The imprinting process occurred at the interface of the emulsions or microemulsions, by the migration of the NAP-surfactant head into the sol-gel drops to leave surficial imprints due mainly to ion-pair interaction with a cationic group contained within the growing sol-gel network. The surface-imprinted microspheric particles exhibited a log-normal size distribution with geometric mean diameter of 3.1MUm. A mesoporous texture was found from measurements of the specific surface area (206m(2)/g) and pore diameter (Dp 2nm). Evaluation of the microspheres as packed HPLC stationary phases resulted in the determination of the selectivity factor against ibuprofen (alpha=2.1), demonstrating the successful imprinting. Chromatographic efficiency, evaluated by the number of theoretical plates (222platescm(-3)), emerged as an outstanding feature among the set of all relatable formats produced before, an advantage intrinsic to the location of the imprinted sites on the surface. The material presented a capacity of 3.2MUmolg( 1). Additionally, exploratory work conducted on their nanoscale counterparts resulted in the production of nanospheres in the size order of 10nm providing good indications of a successful imprinting process. PMID- 26875123 TI - [The new insights of 2015 ESC Pulmonary Hypertension Guidelines]. PMID- 26875124 TI - [Comments on 2015 ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death]. PMID- 26875125 TI - [What is new in 2015 ESC nonST Elevation Acute Coronary Syndrome Guideline?]. PMID- 26875126 TI - Cor triatriatum sinister: a case series. AB - OBJECTIVE: As a highly rare congenital defect, cor triatriatum sinister represents only 0.1% of congenital cardiac anomalies. Depending on the degree of obstruction and the accompanying symptoms, cor triatriatum can be diagnosed at any age. This case series described 5 patients with cor triatriatum sinister who underwent operation. METHODS: Five patients with cor triatriatum sinister were seen at our institution between 2007 and 2013. The demographic characteristics and surgical results of these patients are outlined in this retrospective review. RESULTS: The surgical approach consists of left or right atriotomy, excision of the obstructing membrane, and repair of the associated intracardiac anomalies. After an uneventful postoperative hospital stay, all patients were discharged 5 10 days postoperatively. There were no instances of recurrent constriction after surgical treatment of the cor triatriatum membrane. Patients were followed up for a median of 4 years and were symptom free. CONCLUSION: In the surgical management of this easily and fully treatable congenital cardiac anomaly, it is difficult to determine which atriotomy approach is comparatively more advantageous. However, in the management of cor triatriatum sinister, priority should be given to confirmation of the diagnosis and full resection of the membrane. Thus, the surgeon should not hesitate to perform additional incisions if deemed necessary. PMID- 26875127 TI - Relationship between retinopathy and asymptomatic atherosclerosis determined by measurement of carotid intima-media thickness in patients with type 2 diabetes mellitus. AB - OBJECTIVE: Presence of diabetic retinopathy (DR) may be used as an early marker of atherosclerosis in type 2 diabetes mellitus (DM) patients. This study aimed to investigate the relationship between the presence of DR and carotid intima-media thickness (CIMT), which is an indicator of early atherosclerosis in patients with type 2 DM. METHODS: Thirty DM patients with retinopathy (DR group), 28 DM patients without retinopathy (non-DR group), and 27 healthy controls (control group) were included in the study. CIMT was assessed using a high-resolution B mode ultrasonography device. RESULTS: Mean CIMT was found to be 0.9+/-0.17 mm in the DR group, 0.8+/-0.16 mm in the non-DR group, and 0.7+/-0.13 mm in the control group. CIMT was found to be statistically significantly higher in the DR group compared to the other 2 groups (p<0.001). When multivariate analysis was performed, presence of DR still remained as an independent risk factor for increased CIMT values. CONCLUSION: Presence of DR in type 2 DM patients is an independent risk factor in terms of increased CIMT, which is considered to be a finding of subclinical atherosclerosis. Therefore, we believe that type 2 DM patients with retinopathy should be closely followed in terms of cardiovascular events. PMID- 26875128 TI - [Evaluation of transfer parameters in patients admitted to our hospital with ST elevation myocardial infarction]. AB - OBJECTIVE: Acute coronary syndrom (ACS) is a common disease that causes severe morbidity and mortality. The most important aspect of ST-elevation myocardial infarction (STEMI) as a subgroup of ACS treatment is the rapid reperfusion of arteries. Successful results depend not only on the experience of the center but also on the rapidity in which reperfusion is achieved. In our study, the transfer parameters were evaluated in patients who were admitted to our hospital with STEMI. METHODS: Two hundred consecutive patients (160 males, 40 females) who underwent primary percutaneous coronary intervention (PCI) for acute STEMI between January 2011 and March 2013 were included in our study. Transfer parameters of symptom-to-reperfusion treatment, clinical characteristics, and laboratory parameters were recorded. RESULTS: Thirty-six patients were admitted to our hospital with ambulances; 70 patients were admitted to centers without PCI capability, with a mean transfer time to our hospital of 73.9+/-12.5 min. Median pain-to-first medical contact time was 105 min (range: 5-600 min), and average first medical contact-to-balloon time was 115.5 min (range: 20-414 min). Total pain-to-balloon time in females was significantly higher than males (246 min [range: 70-840 min], 195 min [range: 45-684 min], respectively, p=0.032). Mean pain-to-balloon time was significantly lower in patients delivered to the hospital by ambulance than in patients admitted to emergency departments independently (185 min [range: 45-439 min], 248 min [range: 65-840 min], respectively, p=0.017). CONCLUSION: In this study, our hospital door-to-balloon time was found compatible with the target specified in the European Society of Cardiology and American College of Cardiology STEMI guidelines; however, first medical contact-to-balloon time was found to be above that advised by the current guidelines. PMID- 26875129 TI - [Microvascular obstruction due to thrombosis and fibrin deposition in myocardial infarction]. AB - OBJECTIVE: It is widely known that myocardial damage is not immediately terminated after the elimination of epicardial occlusion in cases of myocardial infarction. In situ thrombosis during epicardial occlusion might contribute to poor myocardial perfusion after reperfusion of an occluded epicardial artery. In the current study, we sought to determine the effects of ischemia and reperfusion on microvascular thrombotic occlusion. METHODS: Thirty male Wistar rats were included in the study. After the rats had been anesthetized and thoracotomized, the left coronary artery was occluded for 30 minutes in the first group, and it was occluded for 30 minutes and reperfused for an additional 20 minutes in the second group. Ten rats were used as a sham-operated control group. After completion of the study protocol, excised heart preparations were analyzed by immunohistochemistry and electron microscopy. RESULTS: A significant difference was found between the infarction plus reperfusion group and the other 2 groups, with respect to microvascular fibrin and thrombocyte deposition in immunohistochemistry analysis. These results were confirmed by morphological examination with electron microscopy. CONCLUSION: In situ fibrin formation accompanies microvascular obstruction in acute myocardial infarction. Our results indicate that additional therapeutic approaches are needed in order to achieve better tissue perfusion in contemporary treatment of acute myocardial infarction after successful reopening of the infarct-related artery. PMID- 26875130 TI - Predictive role of left atrial and ventricular mechanical function in postoperative atrial fibrillation: a two-dimensional speckle-tracking echocardiography study. AB - OBJECTIVE: The aim of this study was to determine the role of left-sided mechanical parameters in postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG). METHODS: Ninety patients with coronary artery disease and normal left ventricular (LV) function in sinus rhythm were enrolled in the study. Preoperative LV and left atrial (LA) mechanics were evaluated by two-dimensional (2D) speckle-tracking echocardiography (STE), including strain and rotation parameters, and volume indices. Patients were monitored in order to detect POAF during the postoperative period. RESULTS: Twenty-three of 90 patients (25.6%) developed POAF. Age (p<0.001) and preoperative beta blocker usage (p=0.001) were the clinical parameters associated with POAF. Left atrial maximum volume index (LAV[max]i) increased, and peak left atrial longitudinal strain (PALS) was impaired in POAF patients (p=0.001, p<0.001, respectively). Left ventricular twist (LVtw) and left ventricular peak untwisting velocity (UntwV) were augmented in POAF patients (p=0.013, p=0.009, respectively). Receiver operating characteristic analysis showed N-terminal pro brain natriuretic peptide (NT-proBNP) levels above 70 pg/ml and predicted POAF with a sensitivity of 74% and specificity of 78% (area under curve: 0.758, 95% confidence interval [CI] 0.631-0.894, p<0.001). Logistic regression analysis demonstrated that age (odds ratio [OR] 1.1, CI 1.01-1.20, p=0.034), preoperative beta blocker usage (OR 8.84, CI 1.36-57.28, p=0.022), NT-proBNP (values >70 pg/ml, OR 22.377, CI 3.286-152.381, p<0.001), PALS (OR 0.86, CI 0.75-0.98, p=0.023), and UntwV (OR 1.02, CI 1.00-1.04, p=0.029) were the independent predictors of POAF. CONCLUSION: The combination of 2D STE, clinical, and biochemical parameters may help predict POAF. PMID- 26875131 TI - Patient characteristics and statin discontinuation-related factors during treatment of hypercholesterolemia: an observational non-interventional study in patients with statin discontinuation (STAY study). AB - OBJECTIVE: The purpose of this study was to identify patient characteristics and statin discontinuation-related factors in patients with hypercholesterolemia. METHODS: A total of 532 patients (age mean+/-SD: 57.4+/-11.5 years; 52.4% women, 47.6% men) with hypercholesterolemia and statin discontinuation were included in this national cross-sectional non-interventional observational study. Data on socio-demographic characteristics of patients, cardiovascular risk factors, past treatment with and discontinuation of statin treatment were collected in one visit. RESULTS: Mean+/-SD duration of hypercholesterolemia was 4.9+/-4.2 years at time of discontinuation of statin treatment. Statin treatment was initiated by cardiologists in the majority of cases (55.8%), whereas discontinuation of statin treatment was decided by patients in the majority of cases (73.7%), with patients with higher (at least secondary education, 80.4%) more likely than those with lower (only primary education, 69.7%) to decide to discontinue treatment (p=0.022). Negative information about statin treatment disseminated by TV programs-mostly regarding coverage of hepatic (38.0%), renal (33.8%), and muscular (32.9%) side effects (32.9%)-was the most common reason for treatment discontinuation. CONCLUSION: The decision to discontinue statin treatment was made at the patient's discretion in 74% of cases, with higher likelihood of patients with higher educational status deciding to discontinue treatment and switch to non-drug lipid-lowering alternatives. Cardiologists were the physicians most frequently responsible for the initiation of the statin treatment; coverage of several non-life-threatening statin side effects by TV programs and patients' lack of information regarding high cholesterol and related risks were the leading factors predisposing to treatment discontinuation. PMID- 26875132 TI - A case of myocardial muscular bridging causing severe hypotension during exercise electrocardiography test. AB - Outlining the severity of the myocardial bridge (MB) is a critical step for selecting the appropriate option among medical, surgical, or angioplasty-based treatments. Invasive treatments are usually preferred if treatment-resistant symptoms are observed or ischemia is proven by tests such as fractional flow reserve or myocardial perfusion scintigraphy (MPS). In this report, we present a patient who developed severe hypotension during treadmill exercise test, even though there were no perfusion defects during adenosine-induced MPS. This case suggests MPS with adenosine is not a good choice for evaluating ischemia in MB patients, as it may cause false negative results. PMID- 26875133 TI - Carbamazepine-induced atrioventricular block in an elderly woman. AB - An 88-year-old woman was admitted to the emergency department after experiencing syncope while in a sitting position. Electrocardiogram showed advanced degree heart block. She has been on low-dose carbamazepine (200 mg/day) for the last year for trigeminal neuralgia (TN). After discontinuation of carbamazepine, the patient returned to normal sinus rhythm. PMID- 26875134 TI - Capecitabine-induced coronary artery vasospasm in a patient who previously experienced a similar episode with fluorouracil therapy. AB - Capecitabine is a chemotherapeutic agent used in the treatment of metastatic colon cancer and metastatic breast cancer. It is metabolized into fluorouracil (5 FU) in the liver; hence, its mechanism of action is similar to that of 5-FU. Cardiac toxicity, although rarely seen, may be of concern in some patients. Although multiple hypotheses have been proposed for the mechanism of cardiotoxicity, coronary vasospasm is the most commonly accepted one, as patients usually present with chest pain resembling acute myocardial infarction. Electrocardiography may demonstrate ST-segment elevation, and cardiac biomarkers may be elevated. Cardiotoxicity with 5-FU has been reported widely. Capecitabine has been shown to be much less cardiotoxic compared to 5-FU, with only a handful of cases reporting cardiotoxicity with capecitabine. There are no cases reporting cardiotoxicity with both 5-FU and capecitabine in the same patient. In this case report, we present a patient with adverse cardiac effect with capecitabine whose previous 5-FU therapy was stopped due to cardiotoxicity. PMID- 26875135 TI - Proximal embolization of Edwards SAPIEN prosthesis in transcatheter aortic valve implantation. AB - Transcatheter aortic valve implantation (TAVI) is considered an alternative therapy in high-risk patients with severe aortic stenosis (AS). However, this minimally invasive procedure carries potential complications, such as valve embolization at time of TAVI. We present a case of balloon-expandable aortic valve embolization which was managed nonsurgically. Valve embolization was managed conservatively, as the patient refused open heart surgery for definitive treatment. The patient was transferred to the intensive care unit in stable hemodynamic condition and discharged 1 week following the procedure. PMID- 26875136 TI - Inappropriate shock and battery switching to "End of Life" in a patient with biventricular ICD during magnetic resonance imaging. AB - Presence of a cardiac pacemaker or implantable cardioverter defibrillator (ICD) is a relative contraindication to magnetic resonance imaging (MRI). Biventricular ICDs are often used in the treatment of advanced heart failure; however, reports on experience with biventricular ICDs are lacking in the literature. In this case report, we describe a pacemaker-dependent patient with a biventricular ICD on whom an MRI of the lumbar spine was performed without having realized the presence of the ICD. PMID- 26875137 TI - Scorpion envenomation-induced acute thrombotic inferior myocardial infarction. AB - The occurrence of a serious cardiac emergency following scorpion envenomation has rarely been reported and, when so, mostly presented as non-ST segment elevation myocardial infarction, cardiogenic shock, or myocarditis. Possible mechanisms include imbalance in blood pressure and coronary vasospasm caused by the combination of sympathetic excitation, scorpion venom-induced release of catecholamines, and the direct effect of the toxin on the myocardium. We report a case of a 55-year-old man who presented with acute inferior wall myocardial infarction (MI) within 2 h of being stung by a scorpion. Coronary angiogram revealed total thrombotic occlusion of the left circumflex artery, which was treated successfully with glycoprotein IIb/IIIa inhibitor, thrombus aspiration, antivenom serum, and supportive therapy. Therefore, life-threatening MI can complicate the clinical course during some types of scorpion envenomation and should be managed as an acute coronary syndrome. PMID- 26875138 TI - Malposition of an atrial pacemaker lead crossing through patent foramen ovale in a patient with ischemic stroke. PMID- 26875139 TI - Left atrial metastasis of Ewing's sarcoma mimicking atrial myxoma. PMID- 26875140 TI - An unusual cause of severe tricuspid stenosis. PMID- 26875141 TI - [A rare complication of percutaneous coronary intervention: aortic pseudoaneurysm]. PMID- 26875142 TI - Criss-cross heart with dextrocardia and transposition of the great arteries: a rare pathology. PMID- 26875143 TI - Combined effects of elevated CO2 and Cd-contaminated water on growth, photosynthetic response, Cd accumulation and thiolic components status in Lemna minor L. AB - The objective of this study was to investigate the combined effects of elevated CO2 and cadmium (Cd) treatments on growth, photosynthetic efficiency and phytoremediation ability in Lemna minor L. Plants of L. minor were exposed to different Cd concentrations (0, 1.5, 2.5 and 5 mg L(-1) Cd) for periods of 24, 48 and 72 h at ambient (AC) and at elevated (EC) CO2 (350 and 700 ppm, respectively). Cadmium concentration, bioconcentration factor, enzyme activities and thiols content enhanced in plants with the increase of Cd treatments, time of exposure and at both CO2 levels. Glutathione levels increased only at AC. Growth, photosynthetic and chlorophyll fluorescence parameters, and the reduced glutathione to oxidized glutathione ratio declined in plants with increasing exposure time, Cd treatments and at both CO2 levels. Our results suggested that the alleviation of toxicity, at low Cd doses, observed in L. minor grown at EC is dependent on both increased photosynthesis and an enhanced antioxidant capacity. PMID- 26875144 TI - The mechanism of degradation of bisphenol A using the magnetically separable CuFe2O4/peroxymonosulfate heterogeneous oxidation process. AB - The removal of bisphenol A (BPA) in aqueous solution by an oxidation process involving peroxymonosulfate (PMS) activated by CuFe2O4 magnetic nanoparticles (MNPs) is reported herein. The effects of PMS concentration, CuFe2O4 dosage, initial pH, initial BPA concentration, catalyst addition mode, and anions (Cl(-), F(-), ClO4(-) and H2PO4(-)) on BPA degradation were investigated. Results indicate that nearly complete removal of BPA (50 mg/L) within 60 min and 84.0% TOC removal in 120 min could be achieved at neutral pH by using 0.6 g/L CuFe2O4 MNPs and 0.3 g/L PMS. The generation of reactive radicals (mainly hydroxyl radicals) was confirmed using electron paramagnetic resonance (EPR). Possible mechanisms on the radical generation from CuFe2O4/PMS system are proposed based on the results of radical identification tests and XPS analysis. The lack of inhibition of the reaction by free radical scavengers such as methanol and tert butyl alcohol suggests that these species may not be generated in the bulk solution, and methylene blue probe experiments confirm that this process does not involve free radical generation. Surface-bound, rather than free radicals generated by a surface catalyzed-redox cycle involving both Fe(III) and Cu(II), are postulated to be responsible for the mineralization of bisphenol A. PMID- 26875145 TI - Nanomechanical characterization of alumina coatings grown on FeCrAl alloy by thermal oxidation. AB - This work studies the feasibility of using repetitive-nano-impact tests with a cube-corner tip and low loads for obtaining quantitative fracture toughness values in thin and brittle coatings. For this purpose, it will be assumed that the impacts are able to produce a cracking, similar to the pattern developed for the classical fracture toughness tests in bulk materials, and therefore, from the crack developed in the repetitive impacts it will be possible to evaluate the suitability of the classical indentation models (Anstins and Laugier) for measuring fracture toughness. However, the length of this crack has to be lower than 10% of the total coating thickness to avoid substrate contributions. For this reason, and in order to ensure a small plastic region localized at the origin of the crack tip, low load values (or small distance between the indenter tip and the surface) have to be used. In order to demonstrate the validity of this technique, repetitive-nano-impact will be done in a fine and dense oxide layer (alpha-Al2O3), which has been developed on the top of oxide dispersion strengthened (ODS) FeCrAl alloys (PM 2000) by thermal oxidation at elevated temperatures. Moreover, it will be shown how it is possible to know with each new impact the crack geometry evolution from Palmqvist crack to half-penny crack, being able to study the proper evolution of the different values of fracture toughness in terms of both indentation models and as a function of the strain rate, epsilon, decreasing. Thereby, fracture toughness values for alpha-Al2O3 layer decrease from ~4.40MPam , for high epsilon value (10(3)s(-1)), to ~3.21MPam, for quasi-static epsilon value (10(-3)s(-1)). On the other hand, epsilon a new process to obtain fracture toughness values will be analysed, when the classical indentation models are not met. These values are typically found in the literature for bulk alpha-Al2O3, demonstrating the use of repetitive-nano impact tests which not only provide qualitative information about fracture resistance of the materials but it also can be used to obtain quantitative information as fracture toughness values in the case of brittle materials. PMID- 26875146 TI - The effects of decellularization and cross-linking techniques on the fatigue life and calcification of mitral valve chordae tendineae. AB - In cases of severely diseased mitral valves (MV), the required treatment is often valve replacement. Bioprosthetic and stentless replacement valves are usually either fully or partially composed of animal derived tissue treated with a decellularization process, a cross-linking process, or both. In this study, we analysed the effects of these treatments on the fatigue properties of porcine MV chordae tendineae (CT), as well as on the calcification of the CT using an in vitro technique. CT were tested in 4 groups; (1) native, (2) decellularized (DC), (3) decellularized and cross-linked with glutaraldehyde (DC-GTH), and (4) decellularized and cross-linked with 1-ehtyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)(DC-EDC). CT were tested in both uniaxial tension, and in fatigue at 10MPa peak stress (1Hz). The cycles to failure (mean+/-SD) for the four groups are as follows; Native- 53,397+/-55,798, DC- 28,013+/-30,634, DC-GTH- 97,665+/-133,556, DC-EDC- 318,601+/-322,358. DC-EDC CT were found to have a slightly longer fatigue life than the native and DC groups. The DC-EDC group also had a marginally lower dynamic creep rate, meaning those CT elongate more slowly. After in vitro calcification, X-ray microtomography was used to determine relative levels of calcification. The DC-EDC and DC-GTH groups had the lowest volume of calcific deposits. Under uniaxial testing, the ultimate tensile strength (UTS) of the DC-GTH CT was statistically significantly reduced after calcification, while the UTS was relatively unchanged for the DC-EDC group. Overall, these results indicate that a treatment of decellularization plus cross linking with EDC may improve the fatigue life of porcine CT, reduce the rate of elongation, and help the CT resist the negative effects of calcification. This may be a preferable treatment in the preparation of porcine MVs for the replacement of diseased MVs. PMID- 26875147 TI - Optimisation of composite bone plates for ulnar transverse fractures. AB - Metallic bone plates are commonly used for arm bone fractures where conservative treatment (casts) cannot provide adequate support and compression at the fracture site. These plates, made of stainless steel or titanium alloys, tend to shield stress transfer at the fracture site and delay the bone healing rate. This study investigates the feasibility of adopting advanced composite materials to overcome stress shielding effects by optimising the geometry and mechanical properties of the plate to match more closely to the bone. An ulnar transverse fracture is characterised and finite element techniques are employed to investigate the feasibility of a composite-plated fractured bone construct over a stainless steel equivalent. Numerical models of intact and fractured bones are analysed and the mechanical behaviour is found to agree with experimental data. The mechanical properties are tailored to produce an optimised composite plate, offering a 25% reduction in length and a 70% reduction in mass. The optimised design may help to reduce stress shielding and increase bone healing rates. PMID- 26875148 TI - Effects of oxygen plasma treatment on interfacial shear strength and post-peak residual strength of a PLGA fiber-reinforced brushite cement. AB - Biodegradable calcium phosphate cements (CPCs) are promising materials for minimally invasive treatment of bone defects. However, CPCs have low mechanical strength and fracture toughness. One approach to overcome these limitations is the modification of the CPC with reinforcing fibers. The matrix-fiber interfacial shear strength (ISS) is pivotal for the biomechanical properties of fiber reinforced CPCs. The aim of the current study was to control the ISS between a brushite-forming CPC and degradable PLGA fibers by oxygen plasma treatment and to analyze the impact of the ISS alterations on its bulk mechanical properties. The ISS between CPC matrix and PLGA fibers, tested in a single-fiber pull-out test, increased up to 2.3-fold to max. 3.22+/-0.92MPa after fiber oxygen plasma treatment (100-300W, 1-10min), likely due to altered surface chemistry and morphology of the fibers. This ISS increase led to more efficient crack bridging and a subsequent increase of the post-peak residual strength at biomechanically relevant, moderate strains (up to 1%). At the same time, the work of fracture significantly decreased, possibly due to an increased proportion of fractured fibers unable to further absorb energy by frictional sliding. Flexural strength and flexural modulus were not affected by the oxygen plasma treatment. This study shows for the first time that the matrix-fiber ISS and some of the resulting mechanical properties of fiber-reinforced CPCs can be improved by chemical modifications such as oxygen plasma treatment, generating the possibility of avoiding catastrophic failures at the implant site and thus enhancing the applicability of biodegradable CPCs for the treatment of (load-bearing) bone defects. PMID- 26875150 TI - Splenomegaly and thrombosis risk in essential thrombocythemia: the Mayo Clinic experience. PMID- 26875151 TI - MicroRNAs and cancer resistance: A new molecular plot. AB - The most common cause of cancer relapse is drug resistance, acquired or intrinsic, which strongly limits the efficacy of both conventional and new targeted chemotherapy. MicroRNAs (miRNAs) are a growing, large family of short noncoding RNAs frequently dysregulated in malignancies. Although the mechanism of miRNA-mediated drug resistance is not fully understood, an increasing amount of evidence suggests their involvement in the acquisition of tumor cell drug resistance, pointing towards the need for novel and more innovative therapeutic approaches. Use of antagomiRs or mimics can modulate specific miRNAs in order to restore gene networks and signaling pathways, perhaps optimizing chemotherapies by increasing cancer cell sensitivity to drugs. The aim of this review is to provide a state-of-the-art scenario with regard to the most recent discoveries in the field of miRNAs involved in the process of resistance to cancer therapy. PMID- 26875153 TI - Discrimination and common mental disorder among migrant and ethnic groups: findings from a South East London Community sample. AB - PURPOSE: Few studies have examined discrimination and mental health in the UK, particularly by migrant status and in urban contexts with greater demographic diversity. This study aims to (1) describe the prevalence of discrimination experiences across multiple life domains; (2) to describe associations between discrimination experiences and common mental disorder (CMD); (3) to determine whether or not the relationship between discrimination and CMD varies by migrant status and ethnicity. METHODS: Data on major, anticipated and everyday discrimination and CMD symptoms were collected from an ethnically diverse prospective sample of 1052 participants followed up from 2008 to 2013 in the South East London Community Health study, a population-based household survey. RESULTS: With few exceptions, discrimination was most prevalent among those in the Black Caribbean group. However, those in the White Other ethnic group had similar or greater reporting major and anticipated discrimination to Black or mixed ethnic minority groups. The effects of discrimination on CMD were most pronounced for individuals who had recently migrated to the UK, an ethnically heterogeneous group, and for Black and Mixed ethnic minority groups in partially adjusted models. Prior CMD accounted for differences between the Mixed and White British ethnic groups, but the strength of the association for the most recent migrant group and the Black ethnic groups remained two or more times greater than the reference groups. CONCLUSIONS: The strength of the relationship suggests a need for more consideration of migration status along with ethnicity in examining the impact of discrimination on mental disorder in community and clinical samples. PMID- 26875152 TI - An examination of the long-term impact of job strain on mental health and wellbeing over a 12-year period. AB - OBJECTIVES: Job strain has been implicated in a range of employee health outcomes including psychiatric health. Much of the literature is drawn from studies that utilise cross-sectional designs, whilst the long-term follow-up of participants is limited. We examine the short and long-term risks of job strain for depression and wellbeing over a 12-year period. In particular, we utilise measures of wellbeing to emphasise the importance of discriminating between indices of subjective and psychological wellbeing that complement measures of mental health. METHODS: Participants (n = 2530) were aged between 40 and 44 years at baseline and were drawn from the Personality and Total Health (PATH) Through Life Project. Participants were observed once every 4 years for 12 years. RESULTS: A high strain job was associated with an increased risk of reporting sub-syndromal [RRR = 1.66 (95 % CI 1.23; 2.25), p < 0.001], minor [RRR = 1.92 (95 % CI 1.19; 3.10), p < 0.001] and major depression [RRR = 2.19 (95 % CI 1.30; 3.67), p < 0.001], but strain was not a long-term risk for depression 4 years later. In contrast, strain was a risk for both cross-sectional and longitudinal wellbeing outcomes. Moving into a high strain job was a risk for developing depression [RRR = 1.81 (95 % CI 1.26; 2.59), p < 0.001], but the cumulative exposure to a high strain job was not associated with poorer outcomes in adjusted models. CONCLUSIONS: Overall, our results emphasise the importance of current job strain, and the risk of moving into a high strain job, on adverse mental health and wellbeing outcomes. Effects were not consistent between indices of mental health, subjective or psychological wellbeing, supporting the need to dedifferentiate between wellbeing and mental health. PMID- 26875154 TI - Adaptive dosing of anticancer drugs in neonates: facilitating evidence-based dosing regimens. AB - PURPOSE: Selection of the most appropriate chemotherapy dosing regimens for neonates treated within the first weeks of life represents a significant clinical dilemma. Due to a lack of information relating to the clinical pharmacology of anticancer drugs in these challenging patients, current dosing guidelines are based on limited scientific rationale. In the current study, we investigate the utilisation of therapeutic drug monitoring approaches in neonates with localised hepatoblastoma, Wilms' tumour and stage 4S neuroblastoma, being treated with widely used anticancer drugs. METHODS: Plasma concentrations of cisplatin, vincristine, etoposide and carboplatin were quantified in two neonates being treated within the first 3 weeks of life and in a 32-week preterm infant treated at a gestational age of 40 weeks. Therapeutic drug monitoring was carried out where appropriate, based on the pharmacokinetic data obtained in conjunction with clinical response and toxicity. RESULTS: Treatment of a child aged 2 weeks with a recommended cisplatin dose reduction for weight to 1.8 mg/kg resulted in achievement of unbound cisplatin plasma concentrations of 0.01-0.08 ug/mL, markedly lower than exposures previously reported in infants and older children. A dose increase to 2.7 mg/kg was implemented, leading to the achievement of levels more in-line with those previously reported. This increased dose level was well tolerated over six courses of treatment, resulting in a good response to cisplatin monotherapy and the patient remains in remission at 3.5 years. In contrast, a 50 % vincristine dose reduction for weight in a 3-week-old neonate resulted in plasma concentrations comparable to levels observed in older children, leading to successful treatment and continued remission at 2 years. In a third patient, etoposide and carboplatin clearance values normalised to body weight were comparable to those reported in older children, resulting in comparatively lower exposures following reduced dosing. CONCLUSIONS: The current report provides unique data on the pharmacokinetics of several widely used anticancer drugs in neonates treated within the first few weeks of life. The provision of these data acts as a useful reference point to support future dosing decisions to be made by clinicians in the treatment of these challenging patients. PMID- 26875149 TI - Contribution of PPARalpha/beta/gamma, AP-1, importin-alpha3, and RXRalpha to the protective effect of 5,14-HEDGE, a 20-HETE mimetic, against hypotension, tachycardia, and inflammation in a rat model of septic shock. AB - OBJECTIVES: We have previously demonstrated that downregulation of the MyD88/TAK1 dependent signaling pathway associated with increased CYP4A1 expression and 20 HETE formation participates in the protective effect of N-(20-hydroxyeicosa 5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE), a 20-HETE mimetic, against vascular hyporeactivity, hypotension, tachycardia, inflammation, and mortality in a rodent model of septic shock. The aim of this study was to determine whether increased renal and cardiovascular expression of PPARalpha/beta/gamma and RXRalpha associated with decreased expression and/or activity of AP-1 and importin-alpha3 participates in the protective effect of 5,14-HEDGE in response to systemic administration of lipopolysaccharide (LPS). METHODS: Conscious male Wistar rats received saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. Separate groups of LPS-treated rats were given 5,14-HEDGE (30 mg/kg) 1 h after injection of saline or LPS. The rats were killed 4 h after saline or LPS administration and the kidney, heart, thoracic aorta, and superior mesenteric artery were collected for measurement of protein expression. RESULTS: Blood pressure fell by 33 mmHg and heart rate rose by 72 beats/min at 4 h after LPS administration. In LPS-treated rats, tissue protein expressions of cytosolic/nuclear PPARalpha/beta/gamma and nuclear RXRalpha, in addition to nuclear translocation of PPARalpha/beta/gamma proteins, were decreased, while cytosolic/nuclear AP-1 subunit c-jun/phosphorylated c-jun and importin-alpha3 protein expression as well as their nuclear translocation were increased. The LPS-induced changes were prevented by 5,14-HEDGE. CONCLUSIONS: The results suggest that an increase in the expression of PPARalpha/beta/gamma and RXRalpha as well as a decrease in AP-1 and importin alpha3 expression/activity participates in the protective effect of 5,14-HEDGE against hypotension, tachycardia, and inflammation during endotoxemia and thus have a beneficial effect in septic shock treatment. PMID- 26875155 TI - Experiences of Participants in a Self-Management Program for Employees with Complaints of the Arm, Neck or Shoulder (CANS): A Mixed Methods Study. AB - Purpose To investigate the experiences of participants of a self-management program for employees with complaints of the arm, neck or shoulder (CANS). The program consisted of six group sessions combined with an eHealth module. Methods Semi-structured interviews with the first 31 consecutive participants of the intervention group participating in a randomized controlled trial. Participants were interviewed after their last group session. Semi-structured interviews were guided by an interview guide and audio-recorded. Data were analyzed using thematic analysis and the emerging themes were discussed. All participants in the intervention group were asked about their experiences with a questionnaire at three (n = 58) and 12-months (n = 53) follow-up. Results Most participants appreciated the diversity of the program and benefited from the interaction with their peers. The eHealth module, although not used by everyone, was generally experienced as positive, especially the section with the physical exercises. Participants obtained more insight into their complaints and increased awareness, which contributed to the acceptance of and coping with the complaints. There was also criticism about the content of the program and the lack of a follow-up session. Results of the questionnaires showed that participants had a high level of satisfaction. Conclusions In general, the intervention fitted the needs of employees with CANS. Participants obtained more knowledge and insight into their complaints, as well as increased awareness; all this contributed to a behavioral change and improved coping. Many participants made changes at work and during their leisure time, whereas some felt that continuing their 'changed' behavior would be a challenge. PMID- 26875156 TI - High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of personalized medicine. AB - Approximately 15 % of colorectal carcinomas (CRC) display high level microsatellite instability (MSI-H) due to either a germline mutation in one of the genes responsible for DNA mismatch repair (Lynch syndrome, 3 %) or somatic inactivation of the same pathway, most commonly through hypermethylation of the MLH1 gene (sporadic MSI-H, 12 %). Although heterogeneous, MSI-H colorectal carcinomas as a group show some distinct biologic characteristics when compared to CRC with stable or low level microsatellite instability. In the present review we will highlight therapeutically relevant characteristics of MSI-H tumors which could lead to specific responses to some conventional chemotherapy or novel targeted therapy agents. PMID- 26875159 TI - History and current status of state graduated driver licensing (GDL) laws in the United States. AB - INTRODUCTION: The objective of this study is to describe changes in teenage driver licensing policies in the United States during the past two decades with the introduction of graduated driver licensing (GDL) programs, assess GDL laws currently in place, and discuss the possibilities and likely consequences of further changes. METHODS: The history of laws introducing and amending GDL programs was tracked, based on records maintained by the Insurance Institute for Highway Safety (IIHS). Counts of states included the District of Columbia. RESULTS: A few states had elements of GDL prior to the mid-1990s, and between 1996 and 2006 all other states adopted a learner period of 2 months or more, a minimum supervised practice hours requirement for the learner period, or a night or passenger restriction once initially licensed. All but seven states have upgraded their original laws one or more times. Very few states weakened their laws, usually in minor ways. In 158 instances, minimum learner periods, minimum practice hour requirements, or night or passenger restrictions were added or strengthened. Fifteen states raised the minimum age for a license allowing any unsupervised driving. CONCLUSION: GDL policies have reduced teenage driver crashes. Most states now have at least minimum requirements for basic GDL features, although there is substantial opportunity for strengthening existing policies. Additional upgrades would result in further crash reductions, but very few have been made in recent years. PRACTICAL APPLICATIONS: Guidelines for maximizing the crash reduction potential of GDL programs are available, based on the experience of U.S. states, other countries with GDL programs, and the evaluation literature in regard to GDL components. PMID- 26875158 TI - Degradation of fluorescent high-visibility colors used in safety garments for the Australian railway industry. AB - INTRODUCTION: This study investigated the compliance of four fluorescent orange high-visibility garment substrates that are predominantly used in the Australian railway industry. While Special Purpose Orange (SPO), a shade of the Fluorescent orange (Fl-orange) is recommended by most Australian states as the high visibility background color of a safety garment, there appear to be variations in the background color of clothing used by line-workers and rail contractors. The color of the garment was assessed for compliance with the Australian Standard AS/NZS 1906.2.2010 for high-visibility materials for safety garments. The results were also compared with ANSI Z535.2011 and BS EN ISO 20471.2013 Standards. METHOD: Photometric and colorimetric assessments of the background color of the garment substrates were performed using a spectrophotometer and were evaluated for compliance with the Standards after washing and exposure to UV. RESULTS: The spectrophotometry measurements showed that Fl-orange background color for all samples except one complied with the AS/NZS 1906.2 Standard for daytime high visibility garments after 20 washes but failed to comply after exposure to UV. It was also found that the chromaticity coordinates of the corners of the Fl-orange color space, specified in the AS/NZS 1906.4.2010 Standard are much wider and yellower when compared with the ANSI Z535.1.2011 and BS EN ISO 20471.2013 Standards. The sample that failed to comply with the Australian and American Standards however complied with the ISO Standard. PRACTICAL APPLICATIONS: Irrespective of the Standard used, the research has shown the degrading effect of washing and light exposure and raises the questions as to how regularly, and under what conditions high-visibility garments need to be replaced. These findings will provide information for safety garment manufacturers about the characteristics and performance of high-visibility safety garments which make them conspicuous during daytime use. This research recommends that colors for railway workers should be chosen based on the conspicuity, commercial viability, reproducibility and durability rather than simply adopting standards from other industry domains or other countries. PMID- 26875157 TI - Mullerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery. AB - More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey, the gynecologic tissues and organs from which the malignancy may arise to disseminate throughout the pelvic and abdominal organs and peritoneum and how this information can be used to reduce the risk and morbidities of intra-abdominal carcinomatosis in effected individuals. PMID- 26875160 TI - Observed child restraint misuse in a large, urban community: Results from three years of inspection events. AB - PROBLEM: Child restraints (CRs) are vital for optimizing child passenger safety and reducing the risk of pediatric injury and fatality in motor vehicle crashes. However, most CRs are installed improperly. METHODS: This present study was an assessment of observed instances of CR misuse. Participants were recruited through advertisements for CR inspection events in Los Angeles County, California. Child Passenger Safety Technicians collected information about each child passenger, vehicle, and aspects of CR selection and installation. RESULTS: Of 693 CRs installed upon arrival, only 3.8% were used with no instances of misuse. The most common misuses were inappropriate use of the top tether and failure to secure the seatbelt in locked mode. CONCLUSIONS: The majority of observed CRs were installed with instances of misuse. CRs in newer vehicles were less likely to be installed in front of airbags and more likely to have the seatbelt routed inappropriately compared to those in older vehicles. Older children were more likely to be prematurely restrained in the front vehicle seat. PRACTICAL APPLICATIONS: The majority of CRs are installed improperly. We identified specific instances of CR misuse that are common in a large, urban community and present recommendations to improve child passenger safety practices and education. PMID- 26875161 TI - Using a cluster randomized controlled trial to determine the effects of intervention of battery and hardwired smoke alarms in New South Wales, Australia: Home fire safety checks pilot program. AB - INTRODUCTION: In 2014, Fire & Rescue New South Wales piloted the delivery of its home fire safety checks program (HFSC) aimed at engaging and educating targeted top "at risk" groups to prevent and prepare for fire. This pilot study aimed to assess the effectiveness of smoke alarms using a cluster randomized controlled trial. METHODS: Survey questionnaires were distributed to the households that had participated in the HFSC program (intervention group). A separate survey questionnaire was distributed to the control group that was identified with similar characteristics to the intervention group in the same suburb. To adjust for potential clustering effects, generalized estimation equations with a log link were used. RESULTS: Multivariable analyses revealed that battery and hardwired smoking alarm usage increased by 9% and 3% respectively among the intervention group compared to the control group. Females were more likely to install battery smoke alarms than males. Respondents who possessed a certificate or diploma (AOR=1.31, 95% CI 1.00-1.70, P=0.047) and those who were educated up to years 8-12 (AOR=1.32, 95% CI 1.06-1.64, P=0.012) were significantly more likely to install battery smoke alarms than those who completed bachelor degrees. Conversely, holders of a certificate or diploma and people who were educated up to years 8-12 were 31% (AOR=0.69, 95% CI 0.52-0.93, P=0.014) and 24% (AOR=0.76, 95% CI 0.60-0.95, P=0.015) significantly less likely to install a hardwired smoke alarm compared to those who completed bachelor degrees. CONCLUSIONS: This pilot study provided evidence of the benefit of the HFSC in New South Wales. PRACTICAL APPLICATIONS: Fire safety intervention programs, like HFSC, need to be targeted to male adults with lower level of schooling even when they are aware of their risks. PMID- 26875162 TI - Night club patrons who feel safe will return: Evidence to encourage management to address club violence. AB - INTRODUCTION: There is substantial evidence that heavy drinking is associated with aggression and violence. Most managers of drinking establishments are required to maintain a security staff to deal with disruptive patrons who threaten an organization's business or legal status. However, managers may focus little on minor instances of aggression even though these may escalate into more serious events. We hypothesize that proactive security efforts may positively affect patrons' perceptions of nighttime safety and influence their decisions to return to the club, thereby affecting the club's bottom line. METHOD: Data for this study were collected from entry and exit surveys with 1714 attendees at 70 electronic music dance events at 10 clubs in the San Francisco Bay Area (2010 2012). Participants were asked to report on observations and experiences with aggressive behavior while in the club, their overall perception of club safety, and their plans to return to the same club in the next 30 days. Mediational multiple regression analysis was used to relate observations of club security to perceptions of personal safety and plans to return to the club. RESULTS: Reported observations of an active club security staff were positively related to perceptions of personal safety. Safety perceptions, in turn, were significantly related to plans to return to the club. The indirect path between perceptions of security and plans to return was significant as well. CONCLUSIONS: The results suggest that an active security presence inside clubs can encourage club attendance by providing an environment where minor altercations are minimized, contributing to the perception of club safety. PRACTICAL APPLICATIONS: Evidence that proactive security efforts appear to increase return customers might motivate managers to implement better security policies. PMID- 26875163 TI - An evaluation of Ontario's Group Education Session (GES) for license renewal of seniors aged 80 and above. AB - INTRODUCTION: In 1996, the Ministry of Transportation in Ontario (MTO) implemented the Group Education Session (GES), which is a mandatory license renewal program for drivers aged 80 and older. This study describes an evaluation of the GES to assess its impact on road safety in Ontario, as well as its effect on the safety of individual drivers who participated in the program. METHODS: Time series analysis of senior driver records both before and after implementation of the GES, and logistic regression and survival analysis examining senior driver records prior to, and following, their participation in the GES. RESULTS: Using time series analysis there is some evidence to suggest that the GES had a positive impact on road safety. According to the other analyses, participation in the GES is associated with a decrease in the odds of collisions and convictions, regardless of whether drivers pass their first attempt of the knowledge test or not. In addition, failing the first road test and/or having demerit points are strong indicators of future collision and conviction involvement. DISCUSSION: Results from this evaluation suggest that the GES has had a protective effect on the safety of senior drivers. PRACTICAL APPLICATIONS: The findings and discussion will help MTO improve the GES program and provide insights to other jurisdictions that have, or are considering, introducing new senior driver programs. PMID- 26875164 TI - Global bike share: What the data tells us about road safety. AB - INTRODUCTION: Bike share has emerged as a rapidly growing mode of transport in over 800 cities globally, up from just a handful in the 1990s. Some analysts had forecast a rise in the number of bicycle crashes after the introduction of bike share, but empirical research on bike share safety is rare. The goal of this study is to examine the impact of bike share programs on cycling safety. METHODS: The paper has two substudies. Study 1 was a secondary analysis of longitudinal hospital injury data from the Graves et al. (2014) study. It compared cycling safety in cities that introduced bike share programs with cities that did not. Study 2 combined ridership data with crash data of selected North American and European cities to compare bike share users to other cyclists. RESULTS: Study 1 indicated that the introduction of a bike share system was associated with a reduction in cycling injury risk. Study 2 found that bike share users were less likely than other cyclists to sustain fatal or severe injuries. CONCLUSIONS: On a per kilometer basis, bike share is associated with decreased risk of both fatal and non-fatal bicycle crashes when compared to private bike riding. PRACTICAL APPLICATIONS: The results of this study suggest that concerns of decreased levels of cycling safety are unjustified and should not prevent decision makers from introducing public bike share schemes, especially if combined with other safety measures like traffic calming. PMID- 26875165 TI - Leader-member exchange: Moderating the health and safety outcomes of job insecurity. AB - INTRODUCTION: Job insecurity has been repeatedly linked with poor employee health and safety outcomes. Although research on high quality leader-member exchange (LMX) has demonstrated many beneficial effects, no research to date has examined the extent to which positive LMX might attenuate those adverse health and safety related consequences of job insecurity. The current study extends research in this area by specifically examining the buffering impact of LMX on the relationship between job insecurity and safety knowledge, reported accidents, and physical health conditions. Furthermore, the study also examines whether positive LMX mitigates the typically seen negative impact of job insecurity on supervisor satisfaction. METHODS: The hypotheses were tested using survey data collected from 212 employees of a mine located in southwestern United States. RESULTS: As predicted, job insecurity was related to lower levels of supervisor satisfaction, more health ailments, and more workplace accidents, and was marginally related to lower levels of safety knowledge. Results indicated that LMX significantly attenuated these observed relationships. CONCLUSIONS: The quality of the dyadic relationship between supervisor and subordinate has a significant impact on the extent to which job insecurity is associated with adverse health and safety outcomes. PRACTICAL APPLICATIONS: Practical implications for supervisor behavior and developing high quality LMX are discussed in light of today's pervasive job insecurity. PMID- 26875166 TI - Analysis of the injury severity of crashes by considering different lighting conditions on two-lane rural roads. AB - INTRODUCTION: Many studies have examined different factors contributing to the injury severity of crashes; however, relatively few studies have focused on the crashes by considering the specific effects of lighting conditions. This research investigates lighting condition differences in the injury severity of crashes using 3-year (2009-2011) crash data of two-lane rural roads of the state of Washington. METHOD: Separate ordered-probit models were developed to predict the effects of a set of factors expected to influence injury severity in three lighting conditions; daylight, dark, and dark with street lights. A series of likelihood ratio tests were conducted to determine if these lighting condition models were justified. RESULTS: The modeling results suggest that injury severity in specific lighting conditions are associated with contributing factors in different ways, and that such differences cannot be uncovered by focusing merely on one aggregate model. Key differences include crash location, speed limit, shoulder width, driver action, and three collision types (head-on, rear-end, and right-side impact collisions). PRACTICAL APPLICATIONS: This paper highlights the importance of deploying street lights at and near intersections (or access points) on two-lane rural roads because injury severity highly increases when crashes occur at these points in dark conditions. PMID- 26875167 TI - Toyota drivers' experiences with Dynamic Radar Cruise Control, Pre-Collision System, and Lane-Keeping Assist. AB - INTRODUCTION: Advanced crash avoidance and driver assistance technologies potentially can prevent or mitigate many crashes. Previous surveys with drivers have found favorable opinions for many advanced technologies; however, these surveys are not necessarily representative of all drivers or all systems. As the technologies spread throughout the vehicle fleet, it is important to continue studying driver acceptance and use of them. METHOD: This study focused on 2010 2013 Toyota Sienna and Prius models that were equipped with adaptive cruise control, forward collision avoidance, and lane departure warning and prevention (Prius models only). Telephone interviews were conducted in summer 2013 with 183 owners of vehicles with these technologies. RESULTS: About 9 in 10 respondents wanted adaptive cruise control and forward collision avoidance on their next vehicle, and 71% wanted lane departure warning/prevention again. Males and females reported some differences in their experiences with the systems; for example, males were more likely to have turned on lane departure warning/prevention than females, and when using this system, males reported more frequent warnings than did females. Relative to older drivers, drivers age 40 and younger were more likely to have seen or heard a forward collision warning. CONCLUSIONS: Consistent with the results in previous surveys of owners of luxury vehicles, the present survey found that driver acceptance of the technologies was high, although less so for lane departure warning/prevention. Experiences with the Toyota systems differed by driver age and gender to a greater degree than in previous surveys, suggesting that the responses of drivers may begin to differ as crash avoidance technology becomes available on a wider variety of vehicles. PRACTICAL APPLICATION: Crash avoidance technologies potentially can prevent or mitigate many crashes, but their success depends in part on driver acceptance. These systems will be effective only to the extent that drivers use them. PMID- 26875168 TI - Urban green spaces activities: A preparatory groundwork for a safety management system. AB - INTRODUCTION: Urban green spaces works and maintenance are high-risk activities and usually represent possible sources of injuries. The management issues are complex and strongly influenced by companies' policies in terms of safety management and human factor. A high number of tasks-including protecting public health and safety and safe working procedures-need to be faced by professional arborists or gardeners. METHOD: The present paper provides a preparatory groundwork for modeling and describing the real risk levels during the abovementioned activities. The methodology represents a useful tool for decision making both for group leaders and safety coordinators. This goal is reached by collecting data emerging from several workplaces located in North East Italy regarding the frequency and severity of injuries. RESULTS: The preliminary results point out that the most frequent injuries in green maintenance activities are represented by cuts, contusions, and ocular lesions, but none of them have lead to particularly serious consequences for the operators; indeed, the high levels of severity are related to traumas, fractures, and acute lumbar herniated discs. The riskiest activities are related to pruning, especially using mobile elevating work platforms, and grass cutting, especially when operated in escarpments and banks. Workers' behavior and companies' safety policies are key elements for a correct safety management system. PMID- 26875169 TI - A pedestrian's smile and drivers' behavior: When a smile increases careful driving. AB - INTRODUCTION: Research has reported that smiles facilitate social relationships. However, the effect of a smile on driving behavior has received less interest. METHOD: This study attempts to evaluate how a pedestrian's smile influences an oncoming driver's behavior. In the first part of our study, male and female research assistants waiting at several pedestrian crossings were asked to smile or not at oncoming drivers. RESULTS: It was found that a smile increases the number of drivers who stop. The same effect was observed when the pedestrian tries to cross outside the pedestrian crossing. Finally, this study shows that motorists drive slower after they see a pedestrian smile, suggesting that a smile can induce a positive mood. PRACTICAL APPLICATIONS: This leads to motorists stopping more readily and driving more carefully. These results also suggest that pedestrians may increase their own safety by using appropriate nonverbal signals toward drivers. PMID- 26875170 TI - Cultural values and random breath tests as moderators of the social influence on drunk driving in 15 countries. AB - INTRODUCTION: The social influence on drunk driving has been previously observed in several countries. It is noteworthy, however, that the prevalence of alcohol in road fatalities is not the same in all countries. The present study aimed to explore whether cultural values and the number of roadside breath tests moderate the link between the perceived drunk driving of one's peers and self-reported behavior. METHODS: Based on the European survey SARTRE 4, the responses of 10,023 car drivers from 15 countries were analyzed. Two cultural values, "tradition" and "conformism," were identified as possibly being linked to social influence. Country scores for these values were taken from the European Social Survey. The number of random roadside breath tests per inhabitant was used as an indicator of drunk-driving enforcement in each country. RESULTS: A hierarchical multilevel modeling analysis confirmed the link between friends' drunk driving and one's own drunk driving in all countries, but the strength of the link was much stronger in some countries (e.g., Italy, Cyprus, and Israel) than in others (e.g., Finland, Estonia, and Sweden). Both the measured value of "tradition" and the number of alcohol breath tests were found to moderate the link between friends' and one's own drunk driving. PRACTICAL APPLICATIONS: European stakeholders should take into account cultural specificities of target countries when designing campaigns against drunk driving. PMID- 26875171 TI - The effects of co-presence on risk perception and intention to engage in risky behaviors. AB - INTRODUCTION: This study investigated the relation between co-presence and bicyclists' riding behavior. We assumed that the presence of peer riders would either facilitate or inhibit risky behaviors depending on bicyclists' perceptions of three traffic contexts conducive to risk taking (i.e., red-light, go straight, and turn to left). METHOD: Young bicyclists (N=207) were randomly assigned to two experimental conditions (alone vs. with peers). They filled in a scenario-based questionnaire about their intentions to adopt risky behaviors in three specific traffic situations as well as their risk perception of these situations and their general self-perceived efficacy as a bicyclist. We hypothesized that the presence of peer riders engaged in a risky behavior will facilitate the intention to adopt risky behaviors in situations where group risk is evaluated as lower than individual risk. In opposition, the presence of peer riders engaged in a risky behavior will inhibit the intention to adopt risky behaviors in situations where group risk is evaluated as higher than individual risk. RESULTS: The results confirmed the hypotheses. PRACTICAL APPLICATIONS: The findings offer insights for developing new effective education and intervention programs in order to reduce the frequency of dangerous behavior among bicyclists. PMID- 26875172 TI - Unintentional injuries treated in hospital emergency departments among persons aged 65 years and older, United States, 2006-2011. AB - INTRODUCTION: With the aging of the United States population, unintentional injuries among older adults, and especially falls-related injuries, are an increasing public health concern. METHODS: We analyzed emergency department (ED) data from the Nationwide Emergency Department Sample, 2006-2011. We examined unintentional injury trends by 5-year age groups, sex, mechanism, body region, discharge disposition, and primary payer. For 2011, we estimated the medical costs of unintentional injury and the distribution of primary payers, plus rates by injury mechanisms and body regions injured by 5-year age groups. RESULTS: From 2006 to 2011, the age-adjusted annual rate of unintentional injury-related ED visits among persons aged >= 65 years increased significantly from 7987 to 8163, per 100,000 population. In 2011, 65% of injuries were due to falls. Rates for fall-related injury ED visits increased with age and the highest rate was among those aged >= 100. Each year, about 85% of unintentional injury-related ED visits in this population were expected to be paid by Medicare. In 2011, the estimated lifetime medical cost of unintentional injury-related ED visits among those aged >= 65 years was $40 billion. CONCLUSION: Increasing rates of ED-treated unintentional injuries, driven mainly by falls among older adults, will challenge our health care system and increase the economic burden on our society. Prevention efforts to reduce falls and resulting injuries among adults aged >= 65 years have the potential to increase well-being and reduce health care spending, especially the costs covered by Medicare. PRACTICAL APPLICATIONS: With the aging of the U.S. population, unintentional injuries, and especially fall-related injuries, will present a growing challenge to our health care system as well as an increasing economic burden. To counteract this trend, we must implement effective public health strategies, such as increasing knowledge about fall risk factors and broadly disseminating evidence-based injury and fall prevention programs in both clinical and community settings. PMID- 26875173 TI - Introduction to the Special Issue on Spinal and Bulbar Muscular Atrophy. AB - This special issue is dedicated to spinal and bulbar muscular atrophy (SBMA) and is based on the conference sponsored by the European Neuromuscular Centre (ENMC) held in March 2015. SBMA, also known as Kennedy's disease, is a neurodegenerative disease caused by an expansion of a repeat of the trinucleotide CAG encoding glutamine in the gene encoding androgen receptor (AR). Expansion of polyglutamine in the AR results in selective lower motor neuron degeneration and skeletal muscle atrophy. SBMA belongs to the family of polyglutamine diseases, which also includes Huntington's disease, dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17. Within the family of polyglutamine diseases, SBMA is unique in its gender-specificity, with full disease manifestation restricted to males. Since the disease is ligand (androgen) dependent, SBMA manifests primarily in males which have high levels of circulating androgens in the serum; females are usually asymptomatic. Indeed, the polyglutamine-expanded AR is converted to a neurotoxic species upon binding to androgens. The mechanisms through which androgen binding triggers the disease are under investigation. Although several therapeutic strategies have been proposed to date, there is currently no effective therapy to arrest or delay disease progression in patients. PMID- 26875175 TI - Impact of the Bowel Management Program on the quality of life in children with fecal incontinence. AB - PURPOSE: Evaluate the impact of implementing Bowel Management Program (BMP) on quality of life (QoL) in children with fecal incontinence (FI). METHODS: Children 3-12 years referred to the Children's Treatment Center of FI were included and categorized accordingto the tendency to constipation (dilated colon; group 1) or diarrhea (non-dilated colon; group 2). Evaluations were performed before and after 3 months of BMP implementation. Perceptions from parents and children about QoL were assessed by the instrument PedsQL4.0 and the severity of FI by the fecal incontinence index (FII) of Wexner scale. RESULTS: 43 children (mean age of 7.7 +/- 3.1) were studied. 32 (74.4 %) belonged to group 1 and 11 (25.6 %) to group 2. After 3 months of BMP, it was noticed a significant improvement of the FII (14.5 +/- 3.7 versus 2.8 +/- 2.5; p < 0.001) in both groups. QoL perception by the parents and children increased on PedsQL4.0 evaluation (p < 0.001). There was a medium inverse statistically significant correlation of the FII and the total PedsQL4.0 score among children and parents (r = -0.47, p = 0.009 and r = -0, 39, p = 0.03, respectively). CONCLUSION: The BMP applied by a multidisciplinary dedicated team significantly improves the QoL of children with FI in the short term period. PMID- 26875176 TI - Recurrent rhabdoid meningioma with lymph node, pulmonary and bone metastases: a diagnostic and therapeutic challenge. AB - Rhabdoid meningioma is a rare meningioma variant, classified as WHO grade III. Although this tumor is known for its aggressive behavior and poor prognosis, extracranial metastasis is rare. We report the rare case of a 31-year-old patient with rhabdoid meningioma which recurred several times despite gross total resection, radiation therapy, and gamma knife radiosurgery, and the last recurrence was associated with metastases to lungs, lymph node and bone. The patient showed no response to paclitaxel-carboplatin, or vincristine cyclophosphamide-adriamycin chemotherapy, and succumbed to the disease. Metastases from rhabdoid meningioma prove to be a diagnostic challenge, and treatment for metastatic meningiomas is not optimized, thus necessitating documentation and interdisciplinary consensus on management protocols. PMID- 26875174 TI - Single-incision laparoscopic surgery (SILS) for children with Crohn's disease. AB - PURPOSE: Single-incision laparoscopic surgery (SILS) has been described in adults with Crohn's disease, but its use in pediatric Crohn's patients has been limited. The purpose of this study was to review our experience with SILS in pediatric patients with Crohn's disease. METHODS: A retrospective review was performed for patients diagnosed with Crohn's disease who underwent small bowel resection or ileocecectomy at a freestanding children's hospital from 2006 to 2014. Data collected included demographic data, interval from diagnosis to surgery, operative time, length of stay, and postoperative outcomes. RESULTS: Analysis identified 19 patients who underwent open surgery (OS) and 41 patients who underwent SILS. One patient (2.4 %) within the SILS group required conversion to OS. Demographic characteristics were similar between the 2 cohorts. The most common indication for surgery was stricture/obstruction (SILS 70.7 % vs. OS 68.4 %, p = 0.86), and ileocecectomy was the most common primary procedure performed (SILS 90.2 % vs. OS 100 % OS). Operative times were longer for SILS (135 +/- 50 vs. 105 +/- 37 min, p = 0.02). However, when the last 20 SILS cases were compared to all OS cases, the difference was no longer statistically significant (SILS 123.3 +/- 34.2 vs. OS 105 +/- 36.5, p = 0.12). No difference was noted in postoperative length of stay (SILS 6.5 +/- 2.2 days vs. OS 7.4 +/- 2.2 days, p = 0.16) or overall complication rate (SILS 24.4 % vs. OS 26.3 %, p = 0.16). CONCLUSION: SILS ileocecectomy is feasible in pediatric patients with Crohn's disease, achieving outcomes similar to OS. As experience increased, operative times also became comparable. PMID- 26875177 TI - Effects of Aqueous Extracts of Chicory and Milk Thistle on Serum Concentrations of Copper, Zinc, and Manganese in Tamoxifen-Treated Rats. AB - Some medications may change trace element levels in the body. Extracts of various plants, due to having the several elements, can have beneficial effects. Consumption of herbal extracts with chemical drugs may reduce adverse effects of medication. The goal of this study was to evaluate copper (Cu), zinc (Zn), and manganese (Mn) concentrations in serum of rats treated with tamoxifen, chicory, and/or milk thistle extracts. Therefore, 36 adult female Wistar rats were divided into six groups: normal control, chicory control, milk thistle control, tamoxifen, tamoxifen-chicory, and tamoxifen-milk thistle. At the end of the study, the blood samples were collected and sera isolated by centrifugation and analyzed by the atomic absorption spectrophotometry for Cu, Zn, and Mn levels. The Zn concentration increased in milk thistle-supplemented groups. The Cu level increased in the chicory control group only. Tamoxifen had no affect on Cu, Zn, and Mn levels, but seed extract of milk thistle increased Zn concentration, and chicory root extract increased Cu concentration. Although elevated levels of Cu in rats receiving tamoxifen-chicory were milder than rats treated only with chicory, it seems that the extract and tamoxifen impact on the Cu are in conflict with each other. PMID- 26875178 TI - Clinical significance of pelvic lymph node status in prostate cancer: review of 1690 cases. AB - To assess whether any relationship exists between the number of histologically examined lymph nodes and the detection of metastases in pelvic lymph node dissection (PLND) specimens taken from patients with radical prostatectomy (RP) for prostatic adenocarcinoma. 1690 cases of RP with PNLD were included in the study; 54 % of the patients were submitted to extended PLND (ePLND). Kaplan-Meier curves confirm the negative prognostic significance of nodal metastases on the overall patients' survival (P < 0.0001). Nodal metastases are significantly associated with older age of patients (P = 0.0466), higher pT status (P < 0.0001), higher Gleason score (P < 0.0001) and positive surgical margin (P < 0.0001). The frequency of nodal metastases is significantly increased in cases submitted to ePLND (P < 0.0001), presumably due to the significantly higher number of lymphnodes retrieved using this procedure (P < 0.0001). In addition, regardless of the extent of PLND procedure, entire histological examination of PLND specimens is significantly associated with a higher frequency of nodal metastases (P < 0.0001). When we considered only pN0 cases, 21 display adverse prognosis and died of disease during the follow-up. The number of pelvic lymphnodes examined is significantly lower in the group of patients who die of the disease compared to that of survivors (P = 0.0448). In addition, Kaplan-Meier analysis shows that patients with 10 or fewer examined lymphnodes have significantly shorter disease-specific survival (P = 0.0151). Our findings confirm the negative prognostic significance of N status in prostate cancer. We suggest the examination of a minimum number of 10 lymphnodes, together with entire PLND processing, for accurate assessment of N status. PMID- 26875179 TI - Direct oral anticoagulants in rare venous thrombosis. AB - The direct inhibitors of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently used in patients with venous thrombosis of the lower or upper limbs or with pulmonary embolism. However, the use of these direct oral anticoagulants (DOACs) in subjects with abdominal or cerebral venous thrombosis is more contentious due to the paucity of available data. In a few case reports and small series of patients hitherto published, the DOACs showed good efficacy and safety, supporting an extension of their use to these rare conditions. Thus, prospective cohort studies and randomized controlled trials have been set up. In this article, we review the published clinical experience with DOACs in rare venous thrombosis, and provide updated information on ongoing clinical trials. PMID- 26875180 TI - Edematous face. PMID- 26875181 TI - The effects of Ni(2+) on electrical signaling of Nitellopsis obtusa cells. AB - The effect of nickel (Ni) on the generation of plant bioelectrical signals was evaluated in Nitellopsis obtusa, a Characean model organism. Conventional glass microelectrode technique and K(+)-anaesthesia method in current-clamp and voltage clamp modes were used for the measurement and analysis of electrical parameters. Ni(2+) treatment rapidly influenced the action potential (AP) parameters namely, excitation threshold, AP peak and duration, membrane potential at various voltages and dynamics of ion currents. We conclude that altered electrical signaling pathway in the test organism constituted the early target for Ni toxicity imposition. The observed Ni interference could be ascribed to disturbed [Ca(2+)]cyt content, impaired Cl(-) and K(+) channels activity resulting in decreased excitability and repolarization rate in generated AP. PMID- 26875182 TI - Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex. AB - Increasing evidence suggests that inorganic arsenic, a major environmental pollutant, exerts immunosuppressive effects in epidemiological, in vitro, and animal models. The mechanisms, however, remain unclear, and little is known about variation in susceptibilities due to age and sex. We performed a review of the experimental and epidemiologic evidence on the association of arsenic exposure and immune diseases. The majority of the studies described arsenic as a potent immunosuppressive compound, though others have reported an increase in allergy and autoimmune diseases, suggesting that arsenic may also act as an immune system stimulator, depending on the dose or timing of exposure. Limited information, due to either the high concentrations of arsenic used in in vitro studies or the use of non-human data for predicting human risks, is available from experimental studies. Moreover, although there is emerging evidence that health effects of arsenic manifest differently between men and women, we found limited information on sex differences on the immunotoxic effects of arsenic. In conclusion, preliminary data show that chronic early-life exposure to arsenic might impair immune responses, potentially leading to increased risk of infections and inflammatory-like diseases during childhood and in adulthood. Further investigation to evaluate effects of arsenic exposure on the developing immune system of both sexes, particularly in human cells and using concentrations relevant to human exposure, should be a research priority. PMID- 26875183 TI - Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth. AB - It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 +/- 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of home care in order to facilitate early identification of children at high risk for stress-related disorders. PMID- 26875184 TI - Clinical predictors of long-term survival in HER2-positive metastatic breast cancer. AB - Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be "exceptional responders" with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. A retrospective, single-institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long term survival. Median overall survival from the time of breast cancer recurrence was 3.9 years (95 % CI 3.4-5.2). From the time of diagnosis of MBC, 56 (33 %) survived for 5 or more years and 12 (7 %) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14 %) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2-12.0) since stopping therapy. In a cohort of patients with HER2 positive MBC treated primarily with trastuzumab and lapatinib, 7 % of patients were "exceptional responders." Combining these clinical factors with molecular determinants of prolonged survival may provide insights for individualizing treatment selection. PMID- 26875185 TI - A phase 1b study of the Akt-inhibitor MK-2206 in combination with weekly paclitaxel and trastuzumab in patients with advanced HER2-amplified solid tumor malignancies. AB - PURPOSE: Akt plays a key role in the aggressive pathogenesis of HER2+ malignancies, suggesting that Akt-inhibitors may be of therapeutic value in the treatment of HER2+ tumors. Preclinical studies demonstrate synergy between MK 2206, a selective allosteric Akt-inhibitor, with paclitaxel and trastuzumab. We aimed to evaluate the safety of this combination in patients with HER2+ malignancies. METHODS: We conducted a phase 1b study of weekly MK-2206 in combination with weekly paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg in patients with HER2+ malignancies. Dose escalation was performed using a modified toxicity probability interval method. Molecular profiling of archived tissue samples and limited PK analyses were performed. RESULTS: 16 patients with HER2+ tumors were enrolled (12 breast, 3 gastric, 1 esophageal). 81 and 75 % had received prior trastuzumab and taxane chemotherapy, respectively. MK-2206 135 mg/week was determined to be tolerable. Three dose-limiting toxicities were observed including two grade 3 rashes and 1 grade 3 neutropenia resulting in a > 7 day delay in treatment. Grade 3/4 adverse events include neutropenia (44 %), rash (13 %), peripheral neuropathy (6 %), and depression (6 %). 10 patients (63 %) demonstrated tumor response (3 complete, 7 partial). Median duration of response was 6 months. Exploratory analyses identified STARD3, TM7SF2, and G3BP1 as potential biomarkers of response. CONCLUSIONS: MK-2206 at a dose of 135 mg/week in combination with weekly paclitaxel and trastuzumab is safe and well tolerated, and is the recommended phase 2 dose for this combination. Preliminary data indicate significant clinical activity in patients with HER2+ tumors despite prior HER2-directed therapy. PMID- 26875186 TI - Phosphorus resorption by young beech trees and soil phosphatase activity as dependent on phosphorus availability. AB - Motivated by decreasing foliar phosphorus (P) concentrations in Fagus sylvatica L. forests, we studied P recycling depending on P fertilization in mesocosms with juvenile trees and soils of two contrasting F. sylvatica L. forests in a greenhouse. We hypothesized that forests with low soil P availability are better adapted to recycle P than forests with high soil P availability. The P resorption efficiency from senesced leaves was significantly higher at the P-poor site (70 %) than at the P-rich site (48 %). P fertilization decreased the resorption efficiency significantly at the P-poor site to 41 %, while it had no effect at the P-rich site. Both acid and alkaline phosphatase activity were higher in the rhizosphere of the P-poor than of the P-rich site by 53 and 27 %, respectively, while the activities did not differ in the bulk soil. Fertilization decreased acid phosphatase activity significantly at the P-poor site in the rhizosphere, but had no effect on the alkaline, i.e., microbial, phosphatase activity at any site. Acid phosphatase activity in the P-poor soil was highest in the rhizosphere, while in the P-rich soil, it was highest in the bulk soil. We conclude that F. sylvatica resorbed P more efficiently from senescent leaves at low soil P availability than at high P availability and that acid phosphatase activity in the rhizosphere but not in the bulk soil was increased at low P availability. Moreover, we conclude that in the P-rich soil, microbial phosphatases contributed more strongly to total phosphatase activity than plant phosphatases. PMID- 26875187 TI - Wetland defense: naturally occurring pesticide resistance in zooplankton populations protects the stability of aquatic communities. AB - Anthropogenic stressors are ubiquitous and have been implicated in worldwide declines of terrestrial and aquatic species. Pesticides are one such stressor that can have profound effects on aquatic communities by directly affecting sensitive species and indirectly affecting other species via trophic cascades, which can alter ecosystem function. However, there is growing evidence that non target species can evolve increased resistance. When such species are important drivers of the food web, then evolved resistance should help buffer communities from the effects of pesticides. To examine this possibility, we cultured four populations of the common zooplankton Daphnia pulex that we previously demonstrated were either sensitive or resistant to a common insecticide (i.e., chlorpyrifos) due to their proximity to agriculture. Using outdoor mesocosms that contained identical aquatic communities of phytoplankton, periphyton, and leopard frog tadpoles (Lithobates pipiens), we manipulated four D. pulex populations and four insecticide concentrations. As we monitored the communities for nearly 3 months, we found that the insecticide caused direct mortality of D. pulex in communities containing sensitive populations, and this led to a bloom of phytoplankton. In contrast, the insecticide caused much less direct mortality in communities containing resistant D. pulex populations, and the trophic cascade was prevented under low to moderate insecticide concentrations. Across all insecticide treatments, survivorship of leopard frogs was approximately 72 % in communities with resistant D. pulex but only 35 % in communities with sensitive D. pulex. To our knowledge, this is one of the first studies to use naturally occurring population variation in insecticide resistance to show that the evolution of pesticide resistance in zooplankton can mitigate the effects of insecticide-induced trophic cascades, and that this outcome can have far-reaching community effects. PMID- 26875188 TI - First Record of the Larval Endoparasitoid Tachinaephagus zealandicus (Hymenoptera: Encyrtidae) From Fly Hosts Developing on Burnt Remains and in Pennsylvania. AB - Adults of the gregarious larval endoparasitoid Tachinaephagus zealandicus Ashmead (Hymenoptera: Encyrtidae) were collected from two species of carrion-inhabiting flies, Phormia regina Meigen (Diptera: Calliphoridae) and Hydrotaea aenescens Wiedemann (Muscidae), associated with the burnt remains of a domesticated pig, Sus scrofa L. (Artiodactyla: Suidae), during late summer in south central Pennsylvania. This represents the first reported occurrence of the wasp in the state and only the second in the mid-Atlantic region. Collection from P. regina is a new host record for T. zealandicus and also the first for this parasitoid being attracted to flies on burnt remains. PMID- 26875189 TI - Conjugation-Mediated Transfer of Antibiotic-Resistance Plasmids Between Enterobacteriaceae in the Digestive Tract of Blaberus craniifer (Blattodea: Blaberidae). AB - Cockroaches, insects of the order Blattodea, seem to play a crucial role in the possible conjugation-mediated genetic exchanges that occur among bacteria that harbor in the cockroach intestinal tract. The gut of these insects can be thought of as an effective in vivo model for the natural transfer of antimicrobial resistance plasmids among bacteria. In our study, we evaluated the conjugation mediated horizontal transfer of resistance genes between Escherichia coli and other microorganisms of the same Enterobacteriaceae family within the intestinal tract of Blaberus craniifer Burmeister, 1838 (Blattodea: Blaberidae). Different in vivo mating experiments were performed using E. coli RP4 harboring the RP4 plasmid carrying ampicillin, kanamycin, and tetracycline resistance genes as the donor and E. coli K12 resistant to nalidixic acid or Salmonella enterica serovar Enteritidis IMM39 resistant to streptomycin as the recipients. The RP4 plasmid was successfully transferred to both recipients, producing E. coli K12-RP4 and S. Enteritidis IMM39-RP4 transconjugants. Conjugation frequencies in vivo were similar to those previously observed in vitro. The transfer of the RP4 plasmid in all transconjugants was confirmed by small-scale plasmid isolation and agar gel electrophoresis, suggesting that the intestinal tract of cockroaches is an effective in vivo model for natural gene transfer. Our results confirm that cockroaches allow for the exchange of antimicrobial resistance plasmids among bacteria and may represent a potential reservoir for the dissemination of antibiotic-resistant bacteria in different environments. These findings are particularly significant to human health in the context of health care settings such as hospitals. PMID- 26875190 TI - How different are composite and traditional TTO valuations of severe EQ-5D-5L states? AB - OBJECTIVE: Different variants of time trade-off (TTO) have been employed to elicit health state preferences and to create value sets for preference-based instruments. We compared composite TTO (cTTO) with traditional TTO (tTTO) in valuing severe EQ-5D-5L health states. METHODS: cTTO uses tTTO to elicit values for health states better than dead and the lead-time TTO for states worse than dead. Eighteen severe states were valued using both cTTO and tTTO. Participants meeting predefined inconsistency criteria were excluded from the analyses. Histograms were used to examine the distributions of cTTO and tTTO values. Mean difference between the cTTO and tTTO values was calculated. Bland-Altman plots were used to examine the agreement between the cTTO and tTTO values for each health state. We used a logistic mixed effects model with random intercepts to identify variables that were associated with the directional change between the two TTO values. RESULTS: A total of 1024 participants were included in the analysis with the mean age (SD) being 47.1 (17.4) years and 54.9 % female. For cTTO, 25 % of the values clustered at zero and there were few values between 0 and -0.5. In contrast, tTTO had fewer values at zero and more falling between 0.5 and 0. The distribution of positive values was similar between cTTO and tTTO. For worse than dead health states, the cTTO values tended to be higher than the tTTO values. In the logistic mixed effects model, those who did not agree that it was easy to understand the cTTO questions more likely changed from positive values in cTTO to zero or negative values in tTTO or change from zero cTTO values to negative values in tTTO compared with those who agreed (odds ratio 1.314, p = 0.037). CONCLUSION: cTTO is an appealing technique in eliciting health state preferences, but further evidence is needed for its performance in valuing EQ-5D health states on a wide spectrum of health state severity. PMID- 26875191 TI - Chronic Migraine in Children and Adolescents. AB - Chronic migraine is defined as having more than 15 headache days in a month, half of these showing migraine features, for at least 3 months. It is a chronic painful syndrome with aspects such as psychiatric comorbid, decreased quality of life, and environmental and intrinsic psychological factors that make face-to face treatment difficult. Children and adolescent migraine differ from adults as a result of growing brain and evolving disorder. In this paper, we will emphasize the definition, diagnosis, epidemiology, burden of life, and management of chronic migraine in children and adolescent. PMID- 26875192 TI - Inflammatory markers and exposure to airborne particles among workers in a Swedish pulp and paper mill. AB - PURPOSE: To study the relationship between exposure to airborne particles in a pulp and paper mill and markers of inflammation and coagulation in blood. METHODS: Personal sampling of inhalable dust was performed for 72 subjects working in a Swedish pulp and paper mill. Stationary measurements were used to study concentrations of total dust, respirable dust, PM10 and PM2.5, the particle surface area and the particle number concentrations. Markers of inflammation, interleukins (IL-1b, IL-6, IL-8, and IL-10), C-reactive protein (CRP), serum amyloid A (SAA), and fibrinogen and markers of coagulation factor VIII, von Willebrand, plasminogen activator inhibitor, and D-dimer were measured in plasma or serum. Sampling was performed on the last day of the work free period of 5 days, before and after the shift the first day of work and after the shifts the second and third day. In a mixed model analysis, the relationship between particulate exposures and inflammatory markers was determined. Sex, age, smoking, and BMI were included as covariates. RESULTS: The average 8-h time-weighted average (TWA) air concentration levels of inhalable dust were 0.30 mg/m(3), range 0.005-3.3 mg/m(3). The proxies for average 8-h TWAs of respirable dust were 0.045 mg/m(3). Significant and consistent positive relations were found between several exposure metrics (PM 10, total and inhalable dust) and CRP, SAA and fibrinogen taken post-shift, suggesting a dose-effect relationship. CONCLUSION: This study supports a relationship between occupational particle exposure and established inflammatory markers, which may indicate an increased risk of cardiovascular disease. PMID- 26875193 TI - Is There a Role for Adjuvant Therapy in R0 Resected Gallbladder Cancer?: A Propensity Score-Matched Analysis. AB - PURPOSE: The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection. MATERIALS AND METHODS: Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors. RESULTS: In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5 year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups. CONCLUSION: The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection. PMID- 26875194 TI - Venous Invasion in Colorectal Cancer: Impact of Morphologic Findings on Detection Rate. AB - PURPOSE: Venous invasion (VI) is widely accepted as a poor prognostic factor in colorectal cancer (CRC), and is indicated as a high-risk factor determining the use of adjuvant chemotherapy in CRC. However, there is marked interobserver and intraobserver variability in VI identification and marked variability in the real prevalence of VI in CRC. MATERIALS AND METHODS: We investigated the detection rate of VI in 93 consecutive cases of T3 or T4 CRC based on the following: original pathology report, review of hematoxylin and eosin (H&E) slides with attention to the "protruding tongue" and "orphan arteriole" signs, and elastic stain as the gold standard. RESULTS: Overall, the detection rate of VI was significantly increased as follows: 14/93 (15.1%) in the original pathology report, 38/93 (40.9%) in review of H&E slides with attention to the "protruding tongue" and "orphan arteriole" signs, and 45/93 (48.4%) using elastic stain. VI detection based on morphologic features showed 77.8% sensitivity and 91.1% specificity and showed a linear correlation (Spearman correlation coefficient, 0.727; p < 0.001) with VI detected by elastic stain. In addition, improved agreement between detection methods (detection on the basis of morphologic features, kappa=0.719 vs. original pathology report, kappa=0.318) was observed using kappa statistics. CONCLUSION: Slide review with special attention to the "protruding tongue" and "orphan arteriole" signs could be used for better identification of VI in CRC in routine surgical practice. PMID- 26875195 TI - Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08. AB - PURPOSE: We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. MATERIALS AND METHODS: Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment. RESULTS: Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. CONCLUSION: Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis. PMID- 26875196 TI - Comparison of Quality of Life and Sexuality between Cervical Cancer Survivors and Healthy Women. AB - PURPOSE: The purpose of this study is to compare quality of life (QoL) and sexual functioning between sexually active cervical cancer survivors and healthy women. MATERIALS AND METHODS: In this cross-sectional study, propensity-score-matched cervical cancer survivors (n=104) and healthy women (n=104) were compared. All women had engaged in sexual activity within the previous 3 months, and cervical cancer survivors showed no evidence of disease after primary treatment. QoL and sexual functioning were assessed using three questionnaires; the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), Cervical Cancer Module (EORTC QLQ-CX24), and the Female Sexual Function Index (FSFI). RESULTS: Significantly higher scores for lymphedema were observed in the cervical cancer survivors group compared with the healthy women group (mean, 20.2 vs. 12.2; p < 0.05). Sexuality, both in terms of sexual activity, sexual enjoyment, and sexual worry (EORTC QLQ-CX24), and in terms of desire, arousal, lubrication, orgasm, satisfaction, and pain (FSFI) were similar between the groups. When the scale of sexual/vaginal functioning in EORTC QLQ CX24 was divided into individual questions, cervical cancer survivors reported shorter vaginal length than the control group, but without statistical significance (mean, 80.6 vs. 85.4; p=0.077). CONCLUSION: Compared with healthy women, sexuality was not impaired in cervical cancer survivors who showed no evidence of disease after primary treatment and engaging in sexual activity. Further prospective cohort studies are warranted to confirm this finding. PMID- 26875197 TI - Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study. AB - PURPOSE: This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study. MATERIALS AND METHODS: This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acute-phase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]). RESULTS: In South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI 1). Triple regimen (corticosteroid-5HT3-RA-neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid-5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2). CONCLUSION: Active management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen. PMID- 26875198 TI - A Multi-centric Bioequivalence Trial in Ph+ Chronic Myeloid Leukemia Patients to Assess Bioequivalence and Safety Evaluation of Generic Imatinib Mesylate 400 mg Tablets. AB - PURPOSE: This study was designed to characterize the pharmacokinetic profile and to assess bioequivalence of the sponsor's test formulation (imatinib mesylate 400 mg tablets) with an innovator product (Gleevec 400 mg tablets, Novartis Pharmaceuticals) under fed conditions, in adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) stabilized on imatinib mesylate 400 mg. In addition, the aim of this study was to monitor the safety profile of investigational medicinal products (IMPs). MATERIALS AND METHODS: A multicenter, randomized, open label, two-period, crossover, single dose bioequivalence study was designed for conduct under fed conditions in 42 adult Ph+ CML patients already stabilized on imatinib 400 mg tablets. Pharmacokinetic parameters Tmax, Cmax, and AUC0-24 were calculated using a non-compartmental model on validated WinNonlin software. Validated SAS software was used for statistical evaluation of data. The safety profile of investigational products was monitored during the course of study by applying a clinical process for recording observed untoward effects postadministration of investigational products. RESULTS: The 90% confidence intervals for the test/reference mean ratios of the ln-transformed PK variables Cmax (99.0%) and AUC0-24 (99.2%) were within an acceptable range of 80%-125%, as per bioequivalence assumptions. Both formulations were well tolerated after oral administration of IMPs. CONCLUSION: The test product was found to be bioequivalent and safe, and thus can be used interchangeably in clinical practice. PMID- 26875199 TI - Identification of Prognostic Risk Factors for Transient and Persistent Lymphedema after Multimodal Treatment for Breast Cancer. AB - PURPOSE: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. MATERIALS AND METHODS: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next follow-up; arm swelling that persisted over two consecutive examinations was considered PLE. RESULTS: At a median follow up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). CONCLUSION: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication. PMID- 26875200 TI - Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma. AB - PURPOSE: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients. MATERIALS AND METHODS: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O'Quigley method, and then analyzed in association with prognosis-overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis. RESULTS: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively). CONCLUSION: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection. PMID- 26875202 TI - Colorectal Cancer Incidence in Korea Is Not the Highest in the World. PMID- 26875201 TI - Robotic Surgery for Rectal Cancer: An Update in 2015. AB - During the last decade, robotic surgery for rectal cancer has rapidly gained acceptance among colorectal surgeons worldwide, with well-established safety and feasibility. The lower conversion rate and better surgical specimen quality of robotic compared with laparoscopic surgery potentially improves survival. Earlier recovery of voiding and sexual function after robotic total mesorectal excision is another favorable outcome. Long-term survival data are sparse with no evidence that robotic surgery offers major benefits in oncological outcomes. Although initial reports are promising, more rigorous scientific evaluation in multicenter, randomized clinical trials should be performed to definitely determine the advantages of robotic rectal cancer surgery. PMID- 26875204 TI - Meeting of the International Task Force for Disease Eradication, November 2015. PMID- 26875203 TI - Systemic Treatments for Metastatic Renal Cell Carcinoma: 10-Year Experience of Immunotherapy and Targeted Therapy. AB - PURPOSE: The purpose of this study is to compare the outcomes of first-line systemic targeted therapy (TT) and immunotherapy (IT) in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: This study was a retrospective review of the data of 262 patients treated with systemic IT or TT with tyrosine kinase inhibitors between 2003 and 2013. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were assessed using Response Evaluation Criteria in Solid Tumor ver. 1.0 criteria and the Kaplan-Meier method with log-rank test. RESULTS: During the median 4.3-month treatment and the 24-month follow-up period, the ORR/PFS/OS of the overall first line and second-line therapy were 41.9%/8.1 months/16.8 months and 27.5%/6.5 months/15.3 months, respectively. The first-line TT/IT/sequential IT had a PFS of 9.3/6.4/5.7 months and an OS of 15.8/16.5/40.6 months (all p < 0.05). The second line of TT/IT had a PFS of 7.1/2.1 months (both p < 0.05) and an OS of 16.6/8.6 months (p=0.636), respectively. Pazopanib provided the best median PFS of 11.0 months (p < 0.001) and a quadruple IT regimen had a superior PFS (p=0.522). For OS, sequential treatment with IT and TT was superior compared to treatment with either IT or TT alone (40.6/16.5/15.8 months, p=0.014). The prognosis according to the Memorial Sloan Kettering Cancer Center model showed that favorable/intermediate/poor risk groups had a PFS of 8.5/10.4/2.3 months, and an OS of 43.1/20.4/5.6 months, respectively. The prognosis calculated using the Heng model showed that the favorable/intermediate/poor risk groups had a PFS of 9.2/3.9/2.7 months, and an OS of 32.4/16.5/6.1months, respectively (all p < 0.001). CONCLUSION: In patients with mRCC, TT provided a better PFS and OS compared with IT. PMID- 26875205 TI - Circulating vaccine-derived poliovirus outbreaks in 5 countries, 2014-2015. PMID- 26875206 TI - Resident Rounds: Part III--Cutaneous Sarcoidosis in a Blepharoplasty Scar. PMID- 26875207 TI - Leslie Klenerman (1929-2015). PMID- 26875209 TI - The U.S. Has the Highest Drug Prices in the World. And Hating Martin Shkreli Won't Be Enough to Change It. PMID- 26875210 TI - Thoughtful Play on Mental Health. PMID- 26875208 TI - Integrating nutrition and child development interventions: scientific basis, evidence of impact, and implementation considerations. AB - The Millennium Development Goals (MDGs) have contributed to unprecedented reductions in poverty and improvement in the lives of millions of men, women, and children in low- and middle-income countries. Yet, hundreds of millions of children under 5 y of age are not reaching their developmental potential. This article reviews the scientific basis for early childhood nutrition and child development interventions, the impact of integrated interventions on children's linear growth and cognitive development, and implementation strategies for integrated nutrition and child development programs. Advances in brain science have documented that the origins of adult health and well-being are grounded in early childhood, from conception through age 24 mo (first 1000 d) and extending to age 5 y (second 1000 d). Young children with adequate nutrition, nurturant caregiving, and opportunities for early learning have the best chances of thriving. Evidence from adoption, experimental, and quasi-experimental studies has shown that stunting prevention is sensitive during the first 1000 d, and sensitivity to child development interventions extends through the second 1000 d. Cognitive development responds to interventions post-1000 d with effect sizes that are inversely associated with initial age and length of program exposure. Integrated interventions need governance structures that support integrated policies and programming, with attention to training, supervision, and monitoring. The MDGs have been replaced by the Sustainable Development Goals (SDGs), with targets for the next 15 y. Achievement of the SDGs depends on children receiving adequate nutrition, nurturant caregiving, and learning opportunities from conception through age 5. PMID- 26875211 TI - End-of-life care: The growing role of PCPs. PMID- 26875212 TI - The Secrets of Financial Flexibility. PMID- 26875213 TI - The value of a pension: Three considerations. PMID- 26875214 TI - Overcoming exchange plan payment challenges. PMID- 26875215 TI - Moving the conversation forward on scope of practice. PMID- 26875216 TI - Turning skilled physicians into strong leaders. PMID- 26875217 TI - The PCMH transition: A radical shift worth making. PMID- 26875218 TI - ABIM: Time to heal thyself. PMID- 26875219 TI - Save your breath. PMID- 26875220 TI - URINARY TRACT INFECTIONS AT AGA KHAN UNIVERSITY HOSPITAL NAIROBI - A ONE YEAR EXPERIENCE. AB - BACKGROUND: In developing countries,most of these patients with urinary tract infections (UTI) are normally treated empirically and urine culture is usual ordered for as a last resort in patients refractory to antibiotic treatment. OBJECTIVE: To explore the possibility of designing empiric antibiotic therapy for symptomatic UTI in patients at Aga Khan University Hospital by looking at the trends of UTI, common pathogens isolated and their antibiotic susceptibility pattern. DESIGN: A retrospective clinical-laboratory study. SETTING: Aga Kahn University Hospital- Nairobi. SUBJECTS: Allpositive urine cultures between January and December 2008 were included in the study. RESULTS: A total of 409 urine specimens were retrieved and analysed and 100 cases had negative cultures. Three hundred and nine cases had positive cultures. Sixty eight point seven percent were females while 31.3% were males with a mean age of 31 years. One hundred and thirty five out of 409 patients (33%) had classical signs and symptoms. In 143 (35%) cases E. coli was isolated. The other cultures were organisms other than E. coli. There was a higher resistance to clotrimazole in E. coli (71%) as compared to non-E. coli organisms (23%. There was a higher resistance rate to Nalidixic acid in non-E. Coli organisms (35%) and higher resistance rate to Augmentin in E. Coli 43 versus 18% (c/f non-E.Coli. Forty patients in the study had predisposing factors for UTI. CONCLUSIONS: It is sometimes warranted to start the patient on empiric antibiotic treatmentbefore culture results are available. Nitrofurantoin, Cefuroxime, Ciprofloxacin have good sensitively rates and are therefore drugs of first choice for the treatment of uncomplicated urinary tract infection provided that the contraindications and specific precautions are noted. PMID- 26875221 TI - PERSPECTIVE ON OPPORTUNITIES FOR RESEARCH AND INTERVENTIONS PROVIDED BY COMMUNITY BASED HEALTH INFORMATION SYSTEM ILLUSTRATED BY THE POTENTIAL USE OF MOTIVATIONAL INTERVIEWING INTERVENTION. AB - BACKGROUND: With the growth of Community-Based Health Information (CBHIS) for decision making and service provision in the low income settings, innovative models of addressing Maternal and Newborn Health (MNH) morbidity and mortality are necessary. World Health Organization (WHO) estimates that five hundred thousand mothers and about three million newborns die each year in middle and low income countries. OBJECTIVES: To stimulate interest in utilisation CBHIS for research and interventions, with an illustration of potential using on Motivational Interviewing intervention. DATA SOURCE: Literature searched electronically, discussion with behavioural experts, health system researchers, and maternal and Newborn Health (MNH) experts, and book reviews. STUDY SELECTION: Broad selection criteria including all current literature relevantsubjects including CBHIS, behaviour change methods and Community MNH. DATA EXTRACTION: A checklist for relevance was used to identify the relevant behaviour change intervention to use in the illustration. DATA SYNTHESIS: A method that met the criteria was identified, and based on a discussion with behavioural experts, the decision to use it the illustration was reached. CONCLUSION: Motivational Interviewing Intervention (MII) should be considered for implementation and study on near-term Pregnant women in a setting where these mothers can be identified and a targeted intervention instituted. PMID- 26875222 TI - EFFECT OF LIGHT INTENSITY ON THE CURE CHARACTERISTICS OF PHOTO-POLYMERISED DENTAL COMPOSITES. AB - OBJECTIVE: To determine the light intensity emitted by light curing units (LCUs) and its effect on the cure characteristics of composites polymerised with it. DESIGN: A laboratory based cross sectional study. SETTING: Public and private dental clinics in Nairobi, Kenya. RESULTS: Thirty five (42.17%) LCUs produced light of intensity <=300mWcm-2 while 43 (51.8%) LCUs had their intensities between 300 and 1200mWcm-2. Mean DOC and surface hardness for the 0-300mWcm-2 LCUs was 1.34mm and 46.60VHN respectively. The mean DOC increased steadily from the lowest intensity group (1.34mm) to the 1200-15OOmWcm-2 group (2.32 mm) and then declined to 1.98mm for the 1500-1800mWcm-2 group. Statistical analysis showed significant differences in the mean DOC (p=0.000) and surface micro hardness (p=0.002) for the different intensity groups. CONCLUSION: Light intensity output of LCUs has a significant influence on the cure characteristics of dental composites with both DOC and surface micro-hardness increasing with increase in light intensity up to 1500mWcm-2. PMID- 26875223 TI - INTERNAL ROOT MORPHOLOGY IN MANDIBULAR FIRST PERMANENT MOLARS IN A KENYAN POPULATION. AB - OBJECTIVE: To determine the internal root morphology and gender variations in mandibular first permanent molars in a Kenyan population. DESIGN: In vitro descriptive cross sectional study. SETTING: School of Dental Sciences, University of Nairobi RESULTS: The mesial root of mandibular first molars had two canals in 96.3% of the teeth in both males and females and-type IV canal configuration was most prevalent in the mesial root. The distal root of the mandibular first molar had one canal in 57.7% of the teeth in males and females. There were significant gender variations in the number of canals and canal configurations in the distal root. Two canals were more prevalent in females (53.6%) compared to males (30.4%) and a single canal was more frequent in males (69.6%) compared to females (46.4%) (P=0.001). Canal types 1, 11 and IV were the most frequent in the mandibular distal root. The gender variation in the frequency of canal types I, II and IV in the distal root was statistically significant (P=0.001). CONCLUSION: Most of the mandibular first molars have three canals (56%). Two canals in the distal root are more frequent among females (53.6%) compared to males (30.4%). PMID- 26875224 TI - IS MISOPROSTOL A SUITABLE ALTERNATIVE TO THE SURGICAL EVACUATION OF INCOMPLETE ABORTION IN RURAL SOUTH-EASTERN NIGERIA? AB - BACKGROUND: Research has demonstrated the effectiveness of misoprostol for treatment of incomplete abortion. However, few studies have focused on the feasibility of treating incomplete abortion with misoprostol at the rural clinic level in sub-Saharan Africa. OBJECTIVE: To determine the effectiveness, safety and acceptability of misoprostol as an alternative to the surgical treatment of incomplete abortion at a rural clinic. DESIGN: Open-label randomised controlled trial. SETTING: A private clinic in Ekeakpara community, Osisioma Ngwa Local Government Area, Abia State, Nigeria. SUBJECTS: Women of reproductive age presenting with incomplete abortion. RESULTS: Regardless of treatment allocation, nearly all women had a complete uterine evacuation with either oral misoprostol or manual vacuum aspiration (misoprostol: 98.8%, MVA: 100%, P = 0.99). Misoprostol users were more likely to report that they were'very satisfied'with the method (75.6% versus 45%, P<0.001). In the 72 hours after treatment, women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration. Women in the misoprostol group were more likely to choose that treatment again (96.9 versus 55.6%; P<0.001) and would recommend it to a friend. CONCLUSION: For treatment of first-trimester uncomplicated incomplete abortion at a rural facility, both MVA and 600 MUg oral misoprostol are safe, effective, and acceptable treatments. Depending on availability of each method and the desires of individual women, either option may be presented to women for the treatment of incomplete abortion. PMID- 26875225 TI - ILIOPSOAS MYOFIBROSITIS - A DIAGNOSTIC CONSIDERATION FOR CHRONIC LOWER ABDOMINAL PAIN IN RURAL KENYA. AB - Diagnosis for lower abdominal pain is always challenging clinically and more so inthe setting of rural Africa. Eighteen cases of sonographically-shownipsilateral enlargement and echo alteration of iliopsoas muscle have been compiled in patients with chronic lower abdominal pain. Seventy percent of the cases were treated with antibiotic and 30% with additional anti-inflammatory drug. A telephone interview follow up was done to nine patients, in which eight reported improvement after treatment. One case was biopsied and shown to be myofibrositis of iliopsoas muscle. PMID- 26875226 TI - Progress on the 2010 IOM Future of Nursing Report and Future Needs. PMID- 26875227 TI - Nephrology Nursing and New Graduates. PMID- 26875228 TI - Sleep Issues with Patients Receiving Hemodialysis. AB - Poor sleep among the general population is understudied, unrecognized, and often not assessed This is especially true for patients receiving hemodialysis. This study used a case study design to examine the impact of hemodialysis treatments on the sleep of two patients as measured by actigraphy and self-reported sleep logs. Patient 1 experienced an average sleep efficiency of 82.3% on non hemodialysis days compared to 75.0% on dialysis days, which resulted in a 7.3 percentage point change and 9.7% better sleep efficiency on non-hemodialysis days. Patient 2 reported sleep efficiency 76.6% on non-hemodialysis days compared to 70.5% dialysis on days, resulting in a 6.1 percentage point change and 8.7% better sleep efficiency on non-hemodialysis days. Actigraphy sleep patterns provided an initial move toward best practice for sleep evaluation in this population. PMID- 26875229 TI - Gastrointestinal Symptoms among African Americans Undergoing Hemodialysis. AB - The incidence of end stage renal disease is more than three times higher in African Americans. Treatment regimens contribute to gastrointestinal (GI) complaints. This study's purpose was to examine the incidence of GI symptoms in African-American patients undergoing hemodialysis. Younger participants were more likely to report mild indigestion, while older participants reported severe indigestion or none at all. Females were more likely to report gastrointestinal symptoms. Commonly reported co-morbidities included hypertension, diabetes, and heart disease. Time on hemodialysis ranged from 1 to 279 months. Those who had been on hemodialysis the longest were more likely to report acid reflux, stomach rumbling and mild diarrhea. This study provides a foundation for early identification of GI symptoms in African-Americans patients undergoing hemodialysis. PMID- 26875230 TI - Work-Related Factors as Predictors of Burnout in Serbian Nurses Working in Hemodialysis. AB - Nurses who work in hemodialysis (HD) are considered highly susceptible to burnout due to their close relationship with incurable patients and handling sophisticated machinery. A total of 210 nurses from 12 state-owned HD centers in the Republic of Serbia anonymously completed a background information questionnaire providingfactual data on nurses' sociodemographic characteristics and working conditions using the Maslach Burnout Inventory--Health Services Survey. Almost half of the nurses (42.9%) were experiencing burnout High emotional exhaustion, high depersonalization, and low level of personal accomplishment were present in 40.9%, 8.6%, and 31.3% of nurses, respectively. The number of children, involuntary choice of current position, and unwillingness to choose the same type of job again were significant predictors of burnout. Our population of nurses working in HD was more affected by emotional exhaustion than their colleagues in other countries, but maintained high level of empathy and feeling ofpersonal accomplishment. PMID- 26875231 TI - Changing Nephrology Nurses' Beliefs about the Value of Evidence-Based Practice and Their Ability to Implement in Clinical Practice. AB - A rapidly evolving healthcare environment demands sound research evidence to inform clinical practice and improve patient outcomes. Over the past several decades, nurses have generated new knowledge by conducting research studies, but it takes time for this evidence to be implemented in practice. As nurses strive to be leaders and active participants in healthcare redesign, it is essential that they possess the requisite knowledge and skills to engage in evidence-based practice (EBP). Professional nursing organizations can make substantial contributions to the move healthcare quality forward by providing EBP workshops similar to those conducted by the American Nephrology Nurses'Association. PMID- 26875232 TI - "Black"-Appearing Peritoneal Effluent. AB - When encountering unusually appearing dialysate effluent from a patient doing peri- toneal dialysis, it is important to review the patient's recent exposures. In the case of "black"-appearing dialysate effluent, consideration needs to be given to the possibility of someone having undergone a colonoscopy and having tattooing with India ink. Nephrology nurses are frequently the first to be notified when there has been a change in the character of a patient's peritoneal dialysis dialysate effluent. This article describes a case of "black"-appearing dialysate and includes some of the potential differentials that were considered in the evaluation process. Even though "black"-appearing dialysate is a rare occurrence, nephrology nurses need to be aware of some of the potential etiologies, including exposure to India ink. PMID- 26875233 TI - Does Hemodialysis Dialysate Potassium Composition Matter?. AB - Dyskalemia is known to cause cardiac arrhythmias and cardiac arrest. In persons undergoing hemodialysis, potassium dialysate composition has been identified as a contributingfactor in addition to co-morbidities, medications, dietary potassium intake, and stage of kidney disease. Current evidence recommends a thorough evaluation of all factors affecting potassium balance, and lower potassium concentration should be used cautiously in patients who are likely to develop cardiac arrhythmias. Nephrology nurses play a key role inpatient assessment and edu- cation related to potassium balance. PMID- 26875234 TI - Medication Adherence in Patients on Chronic Hemodialysis: Practical Applications in Clinical Practice. PMID- 26875235 TI - THE VALUE OF TRAINING. We can all be heroes of our own Hudsons. PMID- 26875236 TI - THE LIFELINE OF HOME IMPROVEMENT AGENCIES. PMID- 26875237 TI - IT PAYS TO BEHAVE LIKE AN INVESTMENT PARTNER. PMID- 26875238 TI - INTEGRATED CARE. New, cutting-edge social networking, the old way. PMID- 26875239 TI - INTEGRATED CARE. GPs can provide the perfect mix for hospitals. PMID- 26875240 TI - OVERVIEW. HOW SPECIALISTS CAN HELP YOU. PMID- 26875241 TI - ANALYSIS. TIME TO THINK AGAIN? PMID- 26875242 TI - EFFICIENCY. MEANINGFUL EFFICIENCIES. PMID- 26875243 TI - LEADERSHIP. DIFFERENT ANGLE. PMID- 26875245 TI - WORKFORCE. BROKERS CAN FIX IT. PMID- 26875244 TI - SERVICE REDESIGN HELP THEM TO HELP THEMSELVES. PMID- 26875246 TI - SERVICE IMPROVEMENT. THE WHOLE OF ME. PMID- 26875247 TI - PATIENT EXPERIENCE. 'A GOOD LEADER PICKS YOU UP'. PMID- 26875248 TI - Big data's big puzzle: Now what?. PMID- 26875249 TI - Word to the wise: Check your contract before you put your data on the cloud. PMID- 26875250 TI - Louisiana election could boost Medicaid expansion in other states. PMID- 26875251 TI - Community health dividends. Systems hope social initiatives will produce better health outcomes and lower costs. PMID- 26875252 TI - Rushing for trauma centers. Better financing drives a building boomlet in Level I trauma centers. PMID- 26875253 TI - Easy on those APPS. MOBILE MEDICAL APPS GAIN SUPPORT, BUT MANY LACK CLINICAL EVIDENCE. PMID- 26875254 TI - SAFETY NET LIFELINE. CHICAGO'S PUBLIC HOSPITAL SYSTEM GETS A BOOST FROM ITS NEW MEDICAID PLAN. PMID- 26875255 TI - ACA problems should come as no surprise. PMID- 26875256 TI - Celebrate the advances of modern medicine, but commit to healing other long-term ills. PMID- 26875257 TI - Software coordinates surgical implant orders. PMID- 26875258 TI - Value-based payment poses challenge to rural hospitals. PMID- 26875259 TI - Largest provider vendors of electronic health-record systems. Ranked by number of providers where company is the primary vendor. PMID- 26875260 TI - [COMPARISON OF EFFECTIVENESS BETWEEN TWO OPERATIVE TECHNIQUES OF CORACOCLAVICULAR LIGAMENT RECONSTRUCTION FOR TREATMENT OF Tossy TYPE III ACROMIOCLAVICULAR JOINT DISLOCATION]. AB - OBJECTIVE: To evaluate and compare the effectiveness of double Endobutton technique and suture anchor combined Endobutton plate in the treatment of Tossy type III acromioclavicular joint dislocation. METHODS: Between May 2010 and March 2014, a retrospective study was preformed on 56 patients with Tossy type III acromioclavicular joint dislocation. The coracoclavicular ligament was reconstructed with double Endobutton technique in 31 cases (Endobutton group), and with suture anchor combined Endobutton plate in 25 cases (Anchor group). There was no significant difference in age, gender, injury causes, injury side, associated injury, medical comorbidities, and disease duration between 2 groups (P>0.05). The operation time, medical device expenses, postoperative complications, preoperative and postoperative Constant-Murley scores, and postoperative Karlsson grading of the injured shoulder were compared between 2 groups. RESULTS: The average operation time in Endobutton group was significantly greater than that in Anchor group (t = 4.285, P = 0.000); there was no significant difference in the medical device expenses between 2 groups (t = 1.555, P = 0.126). Primary healing of incision was obtained in all patients of 2 groups; no early complications of infection and skin necrosis occurred. All patients were followed up 15.6 months on average (range, 11-35 months). During follow-up, some loss of reduction and ectopic ossification in the coracoclavicular gap were observed in 1 case and 6 cases of Endobutton group, respectively. No recurrence of acromioclavicular joint dislocation, implant fixation loosening and broken, and secondary fractures occurred in the other patients. There was significant difference in the incidence of postoperative complications between 2 groups (P = 0.013). Constant-Murley scores of the injured shoulder significantly increased at 9 months after operation when compared with preoperative values in 2 groups (P < 0.05), but no significant difference was observed between 2 groups (P > 0.05). At last follow-up, there was no significant difference in Karlsson grading between 2 groups (Z = -0.628, P = 0.530). CONCLUSION: Both double Endobutton technique and suture anchor combined Endobutton plate have good effectiveness in the treatment of Tossy type III acromioclavicular joint dislocation. But the latter is associated with easier operation, less operation time, and less complications. PMID- 26875261 TI - [SURGICAL HIP DISLOCATION APPROACH FOR TREATMENT OF FEMORAL HEAD FRACTURE]. AB - OBJECTIVE: To discuss the value of surgical hip dislocation approach in the treatment of femoral head fracture. METHODS: A retrospectively analysis was made on the clinical data of 15 patients with femoral head fractures treated through surgical hip dislocation approach between January 2010 and February 2013. There were 11 men and 4 women with an average age of 30.8 years (range, 15-63 years). The causes included traffic accident injury in 9 cases, falling injury from height in 5 cases, and sports injury in 1 case. According to Pipkin typing, 2 cases were rated as type I, 7 cases as type II, 1 case as type III, and 5 cases as type IV. The interval of injury and operation was 2-10 days (mean, 4.1 days). Reduction was performed in 10 patients within 6 hours after injury, and then bone traction was given for 4-6 weeks except 5 patients who received reduction in the other hospital. RESULTS: Primary healing of incision was obtained in all patients after surgery without complications of dislocation and lower limbs deep venous thrombosis. The mean follow-up time was 29.9 months (range, 25-36 months). During follow-up, there was no infection, breakage of internal fixation, or nonunion of femoral greater trochanter fracture. In 3 patients having necrosis of the femoral head, 2 had no obvious symptoms [staging as IIa and IIb respectively according to Association Research Circulation Osseous (ARCO) staging system], and 1 (stage IIIb) had nonunion of the femoral neck fracture, who underwent total hip arthroplasty (THA). In 4 patients having myositis ossificans (2 cases of grade I, 1 case of grade II, and 1 case of grade III based on Brooker grading), no treatment was given in 3 cases and the focus was removed during THA in 1 case. According to the Thompson-Epstein scale at last follow-up, the results were excellent in 9 cases, good in 3 cases, fair in 1 case, and poor in 2 cases, and the excellent and good rate was 80%. CONCLUSION: Surgical hip dislocation approach can not only protect the residual vessels of the femoral head but also fully expose the acetabulum and femoral head, which is the ideal approach for the treatment of femoral head fractures. PMID- 26875262 TI - [IMPACT OF SALTER INNOMINATE OSTEOTOMY ON ACETABULAR MORPHOLOGY AND DIRECTION IN DEVELOPMENTAL DISLOCATION OF THE HIP BY THREE-DIMENSIONAL COMPUTER TOMOGRAPHY]. AB - OBJECTIVE: To investigate the impact of the Salter innominate osteotomy on the acetabular morphology and direction and the relationship between them in children with developmental dislocation of the hip (DDH) by three-dimensional CT. METHODS: Between January 2013 and January 2015, 51 patients with unilateral DDH were treated. All patients were females with an average age of 2 years and 5 months (range, one year and 6 months to 5 years). All the patients underwent open reduction of the hip, Salter innominate osteotomy, proximal femoral osteotomy, and hip cast immobilization for treatment. The data of three-dimensional CT before surgery and at 1 week after surgery were measured and collected as follows: the anterior acetabular index (AAI), posterior acetabular index (PAI), axial acetabular index (AxAI), acetabular anteversion angle (AAA) of the acetabulum, and the distances of the forward, outward, and lateral rotation of the distal osteotomy fragments. The differences of AAI, PAI, AxAI, AAA between before and after surgeries were compared and the difference values of the data with significant difference results were calculated. The relationship between the difference values and the distances of three different rotation directions before and after surgeries were tested by Spearman correlation analysis. RESULTS: There were significant differences in the AAI, PAI, and AAA between before and after surgery (P < 0.05), but no significant difference was found in the AxAI between before and after surgery (t = 0.878, P = 0.384). The difference values of AAI, PAI, and AAA were (4.518 +/- 4.601), (4.219 +/- 6.660), and (3.919 +/- 4.389) degrees respectively. The distances of the outward, lateral, and forward rotation of the distal osteotomy fragments after surgery were (0.420 +/- 0.339), (2.440 +/- 0.230), and (0.421 +/- 0.311) cm. There was a significant correlation between the three different rotation directions and AAI difference (P < 0.05), especialy the outward rotation (r=0.981). There was a correlation between the outward, forward rotation and PAI, AAI differences (P < 0.05), and no significant correlation between the lateral rotation and PAI, AAA was found (P > 0.05). There was a significant correlation between the forward rotation and AAA difference (r = 0.841). CONCLUSION: Salter innominate osteotomy can increase the curvature of the anterior wall of the acetabulum in DDH, but reduce the curvature of the rear wall. At the same time, it can also change the direction of the acetabulum, significantly decrease the acetabular anteversion, but it can not change the depth of the acetabulum. The main factors of the curvature change after Salter innominate osteotomy of DDH is attributable to outward rotation, followed by forward rotation, and the main factor of the acetabular direction change is attributable to forward rotation. PMID- 26875263 TI - [EFFECTIVENESS COMPARISON BETWEEN OPEN AND CLOSED REDUCTION USING ELASTIC STABLE INTRAMEDULLARY NAILING FOR PEDIATRIC SUBTROCHANTERIC FRACTURES]. AB - OBJECTIVE: To compare the effectiveness between open reduction and closed reduction of pediatric subtrochanteric fractures using elastic stable intramedullary nailing (ESIN). METHODS: Between January 2010 and January 2014, 22 children with subtrochanteric fractures were treated by ESIN internal fixation combined with hip cast fixation, and the clinical data were retrospectively reviewed. Closed reduction was used in 12 cases (group A) and mini-open reduction in 10 cases (group B). There was no significant difference in gender, age, sides, fracture causes, type of fracture, complications, and time from injury to operation between 2 groups (P > 0.05). The operation time, intraoperative blood loss, fracture healing time, and complications were recorded and compared between 2 groups, the limb function was evaluated according to the Flynn et al. outcome score. RESULTS: The intraoperative blood loss of group A was significantly less than that of group B, but the operation time of group A was significantly longer than that of group B (P < 0.05). All the patients were followed up 12-36 months (mean, 14.9 months). There was no major complications in the other patients of both groups except 1 patient having delayed wound healing in group B. There was no significant difference in fracture healing time between 2 groups (t = -1.006, P = 0.327). Inverted angle of 10 degrees and shortened limb of 1.8 cm were observed in 1 case of group A, and sagittal plane angle of 15 degrees and shortened limb of 2 cm in 1 case of group B. There was no abnormal walking and function of hip and knee activity at last follow-up. According to the Flynn et al. outcome score, the results were excellent in 8 cases and good in 4 cases in group A, and were excellent in 6 cases and good in 4 cases in group B, showing no significant difference between 2 groups (chi2 = 0.041, P = 0.956). CONCLUSION: Both closed and open fracture reduction using ESIN have satisfactory outcomes for treating pediatric subtrochanteric fractures. A mini-open reduction should be selected intraoperatively if closed reduction proves to be difficult. PMID- 26875264 TI - [EFFECTIVENESS OF UC ULTRA-CONGRUENT ROTATING PLATFORM PROSTHESIS IN TREATMENT OF KNEE OSTEOARTHRITIS]. AB - OBJECTIVE: To explore the effectiveness of UC ultra-congruent rotating platform prosthesis in the treatment of knee osteoarthritis by comparing with fixed bearing implant. METHODS: The clinical data were retrospectively analyzed, from 98 patients (98 knees) with knee osteoarthritis undergoing primary total knee arthroplasty between January 2011 and December 2012. The UC ultra-congruent rotating platform prosthesis was used in 56 cases (mobile-bearing group) and fixed-bearing implant was used in 42 cases (fixed-bearing group). There was no significant difference in gender, age, side, weight, disease duration, grading of arthritis, the number of varus and valgus malformation, preoperative range of motion of the knee, the Knee Society Score (KSS) score, the visual analogue scale (VAS) score, femorotibial angle, tibial angle, and articular surface angle between 2 groups (P > 0.05). The operation time (including anesthetic time), intraoperative blood loss, hospitalization time, total hospitalization expenses, postoperative range of motion of the knee, the KSS score, and the VAS score were compared. The femorotibial angle, tibial angle, and articular surface angle were measured on the basis of anteroposterior and lateral X-ray films, and prosthesis loosening was observed. RESULTS: There was no significant difference in the operation time, intraoperative blood loss, and hospitalization time between 2 groups (P > 0.05), while the total hospitalization expenses of fixed-bearing group were significantly lower than those of the mobile-bearing group (t = 8.506, P = 0.000). The patients were followed up 16-30 months in the mobile-bearing group, and for 16-38 months in the fixed-bearing group. Postoperative complications occurred in 3 cases (7.14%) of the fixed-bearing group (1 case of fat liquefaction of incision, 1 case of joint stiff, and 1 case of anterior knee pain), and in 3 cases (5.36%) of the mobile-bearing group (1 case of delayed wound healing, and 2 cases of anterior knee pain); there was no significant difference in the complication rate between 2 groups (chi2 = 0.133, P = 0.516). At last follow-up, the KSS score, VAS score, range of motion of the knee, femorotibial angle, tibial angle, and articular surface angle were superior significantly to those before operation in both groups (P < 0.05), but no significant difference was found between 2 groups (P > 0.05). No radiographic signs of radiolucent line, prosthetic dislocation, patellar dislocation, prosthetic loosening, and fracture was found. CONCLUSION: UC ultra-congruent rotating platform prosthesis in the treatment of knee osteoarthritis can effectively improve the knee joint function and relief pain, which has the same short-term effectiveness in fixed bearing implant. PMID- 26875265 TI - [BONE TRANSPORTATION BY RING TYPE EXTERNAL FIXATOR COMBINED WITH LOCKED INTRAMEDULLARY NAIL FOR TIBIAL NON-INFECTIOUS DEFECT]. AB - OBJECTIVE: To explore the effectiveness of bone transportation by ring type extenal fixator combined with locked intramedullary nail for tibial non infectious defect. METHODS: Between June 2008 and October 2012, 22 cases of tibial large segment defect were treated. There were 15 males and 7 females, aged 24-58 years (mean, 36.8 years), including 17 cases of postoperative nonunion or malunion healing, and 5 cases of large defect. After debridement, bone defect size was 5.0-12.5 cm (mean, 8.05 cm). Bone transportation was performed by ring type external fixator combined with locked intramedullary nail, the mean indwelling duration of external fixation was 10.2 months (range, 2-26 months); the external fixation index was 1.57 months/cm (range, 0.3-3.2 months/cm); and the mean length increase was 8.05 cm (range, 5.0-12.5 cm). RESULTS: All patients were followed up 19-58 months (mean, 32 months). No infection occurred after operation and all patients obtained bony union, and the union time was 4.7-19.4 months (mean, 11.9 months). Complications included refracture (1 case), skin crease (1 case), lengthening failure (1 case), foot drop (2 cases), retractions of the transport segment (1 case), delay of mineralization (1 case), which were cured after corresponding treatment. According to Hohl knee evaluation system to assess knee joint function after removal of external fixator and intramedullary nail, the results were excellent in 15 cases, good in 5 cases, and fair in 2 cases, with an excellent and good rate of 90.9%; according to Baird-Jackson ankle evaluation system to evaluate ankle joint function, the results were excellent in 10 cases, good in 3 cases, fair in 7 cases, and poor in 2 cases, with an excellent and good rate of 59.1%. CONCLUSION: Bone transportation by ring type external fixator combined with locked intramedullary nail could increase stability of extremities, allow early removal of external fixator and avoid axis shift of extremities, so it has good effect in treating tibial noninfectious defect. PMID- 26875267 TI - [EFFECTIVENESS COMPARISON OF ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION BY LONG FIBULAR MUSCLE TENDON AND HAMSTRING TENDON]. AB - OBJECTIVE: To compare the effectiveness of anterior cruciate ligament (ACL) reconstruction between by long fibular muscle tendon and by hamstring tendon under arthroscopy after ACL rupture. METHODS: Between February 2010 and December 2012, 56 cases of ACL rupture underwent ACL reconstruction under arthroscopy. The long fibular muscle tendon was used in 26 cases (group A) and the hamstring tendon was used in 30 cases (group B). There was no significant difference in gender, age, side, disease duration, and preoperative Lachman test, Lysholm score, and the International Knee Documentation Committee (IKDC) score between 2 groups (P > 0.05). The treatment after operation was identical in 2 groups. RESULTS: Primary healing of incision was obtained after operation in 2 groups. There was no major neurovascular injury and knee synovitis. There was no significant difference in operation time, hospitalization time, and postoperative 24-hour drainage volume between 2 groups (P > 0.05). The patients were followed up 25-32 months (mean, 28 months) in group A, and 27-37 months (mean, 31 months) in group B. There was no related complication at donor site in 2 groups. MRI examination showed good ACL reconstruction. The Lysholm score and the IKDC score of group A at 6 months after operation were significantly better than those of group B (P < 0.05), but no significant difference was found between 2 groups at 2 years after operation (P > 0.05). There was no significant difference in Lachman score between 2 groups at 6 months and 2 years after operation (P > 0.05). CONCLUSION: The long fibular muscle tendon for arthroscopic reconstruction of ACL has much simpler operation, earlier knee function recovery, and better subjective satisfaction than the hamstring tendon. PMID- 26875266 TI - [EFFECTIVENESS OF ARTHROSCOPIC ULTRA-Braid SUTURE PLANE FIXATION FOR ANTERIOR CRUCIATE LIGAMENT TIBIAL EMINENCE AVULSION FRACTURES]. AB - OBJECTIVE: To investigate the surgical technique and effectiveness of arthroscopic ULTRA-Braid suture plane fixation for anterior cruciate ligament (ACL) tibial eminence avulsion fractures. METHODS: Between June 2012 and October 2014, 16 cases of ACL tibial eminence avulsion fracture were treated with ULTRA Braid suture plane fixation under arthroscopy. There werg 10 males and 6 females, aged from 17 to 38 years (mean, 25.8 years). The left knee was involved in 5 cases and the right knee in 11 cases. The causes were traffic accident injury in 9 cases, falling from height injury in 4 cases, and sports injury in 3 cases. The average interval from injury to operation was 7 days (range, 5-10 days) except 1 patient who received operation at 6 weeks after injury. The knee joint swelling was obvious; the result of Lachman test was positive; and the knee joint Lysholm score was 45.38 +/- 9.87. According to classification standard introduced by Meyers-McKeever-Zaricnyj, 7 cases were rated as type II, 8 cases as type III, and 1 case as type IV, excluding ligament and meniscus injury. RESULTS: All the incisions healed by first intention. The patients received follow-up of 6-18 months (mean, 10 months). The postoperative X-ray and CT showed anatomic reduction (12 cases) or near anatomic reduction (4 cases); all fractures healed at 6 months after operation. The result of Lachman test was negative in the other 15 patients except 1 patient (II degree). One patient had slight knee pain at 6 months postoperatively, and pain symptom disappeared after 1 year; the other cases resumed daily activities. Lysholm score at last follow-up was 98.13 +/- 2.34, showing significant difference when compared with preoperative score (t = 20.801, P = 0.000). CONCLUSION: Arthroscopic ULTRA-Braid suture plane fixation for ACL tibial eminence avulsion fractures is an effective procedure with the advantages of minimal trauma, reliable fixation, satisfactory functional recovery, and simultaneously avoiding the second surgery. PMID- 26875268 TI - [ARTHROSCOPIC SINGLE BUNDLE POSTERIOR CRUCIATE LIGAMENT RECONSTRUCTION USING HAMSTRING TENDONS THROUGH POSTERIOR TRANS-SEPTUM PORTAL APPROACH WITH PRESERVATION OF REMNANT POSTERIOR CRUCIATE LIGAMENT FIBERS]. AB - OBJECTIVE: To introduce the arthroscopic single bundle posterior cruciate ligament (PCL) reconstruction using hamstring tendons through posterior trans septum portal approach with preservation of the remnant PCL fibers, and to evaluate the clinical results. METHODS: Between June 2010 and April 2014, 57 patients with PCL rupture were treated with arthroscopic single bundle PCL reconstruction using hamstring tendons through posterior trans-septum portal approach with preservation of the remnant PCL fibers. There were 41 males and 16 females, aged 19-42 years (mean, 27.7 years). All the patients had history of injury. The results of posterior drawer test were positive, including 9 cases of grade II and 48 cases of grade III. The disease duration ranged from 2 weeks to 25 months (mean, 13 months). The Lysholm score and the range of motion of knee joint were used to evaluate the knee function. RESULTS: The operation performed smoothly, and no complications of blood vessel and nerve injuries and infection occurred. Primary healing was obtained in all incisions; no early complication occurred after operation. The patients were followed up 16.6 months on average (range, 12-20 months). At last follow-up, the knee range of motion returned to normal in all cases (120-130 degrees in flexion). MRI at last follow-up showed good continuity of the PCL graft and complete healing of the remnant PCL tissues between the femoral and tibial attachments. The Lysholm score was significantly improved when compared with preoperative score (t= -27.429, P = 0.000). CONCLUSION: Arthroscopic single bundle PCL reconstruction using hamstring tendons through posterior trans-septum portal approach with preservation of the remnant PCL fibers has the advantages of firm fixation, simple operation, and good knee function recovery. PMID- 26875269 TI - [EXPERIMENTAL STUDY ON DIFFERENT CONCENTRATION RATIOS OF OSTEOPROTEGERIN COMBINED WITH DEPROTEINIZED BONE ON BONE TUNNEL AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION]. AB - OBJECTIVE: To investigate the effects of different concentrations of osteoprotegerin (OPG) combined with deproteinized bone (DPB) on the bone tunnel after the anterior cruciate ligament (ACL) reconstruction. METHODS: The femoral epiphyseal side was harvested from newborn calf, and allogenic DPB were prepared by hydrogen peroxide-chloroform/methanol method. Then, DPB were immersed in 3 concentrations levels of OPG (30, 60, 100 ug/mL) and 3 concentration ratios (30%, 60%, 100%) of the gel complex were prepared. Sixty healthy New Zealand white rabbits, male or female, weighing (2.7 +/- 0.4) kg, were divided randomly into 4 groups (n = 15): control group (group A), 30% (group B), 60% (group C), and 100% (group D) OPG/DPB gel complex. The ACL reconstruction models were established by autologous Achilles tendon. Different ratios of OPG/DPB gel complex were implanted in the femoral and tibial bone tunnel of groups B, C, and D, but group A was not treated. The pathology observation (including the percentage of the femoral bone tunnel enlargement) and histological observation were performed and the biomechanical properties were measured at 4, 8, and 12 weeks after operation. RESULTS: One rabbit died of infection in groups A and D, 2 rabbits in groups B and C respectively, and were added. General pathology observation showed that the internal orifices of the femoral and tibia tunnels were covered by a little of scar tissue at 4 weeks in all groups. At 8 weeks, white chondroid tissues were observed around the internal orifices of the femoral and tibia tunnels, especially in groups C and D. At 12 weeks, the internal orifices of the femoral and tibia tunnels enlarged in groups A, B, and C, but it was completely closed in group D. At each time point, the rates of the femoral bone tunnel enlargement in groups B, C, and D were significantly lower than that in group A, and group D was significantly lower than groups B and C (P < 0.05); group C was significantly lower than group B at 8 weeks, but no significant difference was found at 4 and 12 weeks (P < 0.05). Hisological observation showed that fresh fibrous connective tissue was observed in 4 groups at 4 weeks; there was various arrangements of Sharpey fiber in all groups at 8 weeks and the atypical 4-layer structure of bone was seen in group D; at 12 weeks, Sharpey fiber arranged regularly in all groups, with typical 4-layer structure of bone in groups B, C, and D, and an irregular "tidal line" formed, especially in group D. Biomechanics measurement showed that the maximum tensile load in group D was significantly higher than that in groups A and B at 4 weeks (P < 0.05), but no significant difference was shown among groups A, B, and C, and between groups C and D (P > 0.05); at 8 weeks, it was significantly higher in groups C and group D than group A, and in group D than group B (P < 0.05), but there was no significant difference between groups A, C and group B (P > 0.05); at 12 weeks, it was significantly higher in groups C and D than groups A and B, and in group D than group C (P < 0.05), but difference was not significant between groups A and B (P > 0.05). CONCLUSION: Different concentrations ratios of OPG/DPB gel complexes have different effects on the bone tunnel after ACL reconstruction. 100% OPG/DPB gel complex has significant effects to prevent the enlargement of bone tunnel and to enhance tendon bone healing. PMID- 26875270 TI - [EXPRESSION AND FUNCTION OF HIGH MOBILITY GROUP BOX CHROMOSOMAL PROTEIN 1 IN SYNOVIOCYTES OF PATIENTS WITH OSTEOARTHRITIS]. AB - OBJECTIVE: To explore the pathological role of high mobility group box chromosomal protein 1 (HMGB1) in osteoarthritis (OA) by comparing the difference of HMGB1 in the synoviocytes between OA and normal knees. METHODS: Synoviocyte lines from OA and normal knees were collected and cultured. Immunohistochemistry and Western blot were applied to identify the difference of HMGB1 between the OA and normal synoviocyte lines. The eukaryotic expression vector containing human Pgenesil-1/HMGB1 small interfering RNA (siRNA) were constructed and identified. The synoviocyte lines were transfected with the eukaryotic expression vector of Pgenesil-1/HMGB1 siRNA (Pgenesil-1/HMGB1 siRNA group) and with Pgenesil-1 plasmid (Pgenesil-1 group) and were not transfected as a control (untransfected group). Western blot was applied to identify the difference of HMGB1 among groups, and the levels of interleukin 1beta (IL-1beta) and tumor necrosis factor alpha (TNF alpha) protein synthesis in the supernatants were measured by ELISA. RESULTS: Primary knee synoviocytes cultured in vitro were fibroblast-like cells with long- spindle shape. The immunohistochemistry and immunofluorescence results showed positive staining for HMGB1 in cytoplasm and weak positive staining in the nucleus in the OA synoviocyte line, but positive staining for HMGB1 in the nucleus and weak positive staining in the cytoplasm in the synoviocyte line of normal knee. The level of HMGB1 in the OA synoviocytes (0.687 +/- 0.025) was significantly higher than that of normal synoviocytes (0.172 +/- 0.030) (t = 32.159, P = 0.000) by Western blot. The recombinant plasmid Pgenesil-1/HMGB1 siRNA was successfully constructed. The expression of HMGB1 protein in Pgenesil 1/HMGB1 siRNA group (0.134 +/- 0.048) was significantly lower than that of Pgenesil-1 group (0.581+/- 0.032) and untransfected group (0.514 +/- 0.069) (P < 0.05). ELISA results showed that IL-1beta and TNF-alpha in supernatants of Pgenesil-1/HMGB1 siRNA group were significantly lower than those of Pgenesil-1 group and untransfected group (P < 0.05). CONCLUSION: The up-regulated expression and expressed location (from nucleus to cytoplasm) of HMGB1 in the synoviocyte are closely related to CA. The siRNA targeting inhibition of HMGB1 gene expression can obviously inhibit II-lp and TNF-a in supernatants of the CA synoviocyte line and delayed the inflammation of CA. PMID- 26875271 TI - [CLINICAL APPLICATION OF INDIVIDUALIZED REFERENCE MODEL OF SAGITTAL CURVES AND NAVIGATION TEMPLATES OF PEDICLE SCREW BY THREE-DIMENSIONAL PRINTING TECHNIQUE FOR THORACOLUMBAR FRACTURE WITH DISLOCATION]. AB - OBJECTIVE: To evaluate the clinical significance of individualized reference model of sagittal curves and navigation templates of pedicle screw by three dimensional printing technique for thoracolumbar fracture with dislocation. METHODS: Between February 2011 and November 2013, 42 patients with thoracolumbar fracture and dislocation undergoing pedicle screw fixation were divided into 2 groups: traditional pedicle screw internal fixation by fluoroscopy assistant was used in 24 cases (control group), and individualized reference model of sagittal curves and navigation templates of pedicle screw were used in 18 cases (trial group). There was no significant difference in gender, age, injury causes, segment, degree of dislocation, and Frankel classification between 2 groups (P > 0.05). The operation time, intraoperative blood loss, perspective times, and dislocation rate, sagittal angle recovery rate at different time were compared. The success rate of pedicle screw insertion, sagittal screw angle, and Frankel classification were compared. The angle between sagittal screws, difference of screw entry point at horizontal position, and difference of screw inclined angle were compared. RESULTS: The operating time, intraoperative blood loss, and perspective times in trial group were significantly lower than those in control groups (P < 0.05). All the patients were followed up 12-40 months (mean, 22 months). The dislocation rate at immediate after operation and last follow-up were significantly improved when compared with preoperative value in 2 groups (P < 0.05). At immediate after operation and last follow-up, the dislocation rate and sagittal angle recover rate in trial group were significantly better than those in control group (P < 0.05). There were significant differences in the one time success rate, final success rate of pedicle screw insertion, and saggital screw angle between 2 groups (chi2 = 9.38, P = 0.00; chi2 = 10.95, P = 0.00; chi2 = 13.43, P = 0.00). The angle between sagittal screws, difference of screw entry point at horizontal position, and difference of screw inclined angle in trail group were significantly less than those in control group (P < 0.05). There was significant difference in the Frankel classification between 2 groups at last follow-up (Z = -1.99, P = 0.04). CONCLUSION: The application of individualized reference model of sagittal curves and navigation templates of pedicle screw by three-dimensional printing technique for thoracolumbar fracture with dislocation has the advantages of shorter operation time, less intraoperative blood loss, better recovery of thoracolumbar dislocation, and better Frankel classification. PMID- 26875272 TI - [COMPARISON OF EFFECTIVENESS AND RADIOLOGICAL FEATURES BETWEEN SINGLE AND DOUBLE CAGE IMPLANTING THROUGH UNILATERAL TRANSFORAMINAL LUMBAR INTERBODY FUSION]. AB - OBJECTIVE: To compare the effectiveness and imaging features between implanting single and double Cage into intervertebral body through unilateral transforaminal lumbar interbody fusion (TLIF). METHODS: The clinical data were collected and analyzed from 104 patients who underwent unilateral TLIF between January 2013 and October 2014, who were divided into 2 groups: single Cage was implanted into intervertebral body in 64 cases (76 segments) in traditional group, and double Cage was implanted into intervertebral body in 56 cases (70 segments) in reformative group. There was no significant difference in age, gender, bone mineral density, operation segments between 2 groups (P > 0.05). The visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopedic Association (JOA) scores were used to evaluate the effectiveness; the area of intervertebral bone-graft, fusion rate, height of intervertebral space, and the number of Cage subsidence were measured by CT scan. RESULTS: All the patients were followed up 12.85 months on average (range, 9-15 months). The VAS, ODI, and JOA scores were significantly improved at each time point after operation when compared with preoperative values (P < 0.05), and no significant difference was found between 2 groups (P > 0.05) except VAS and ODI at 12 months after operation (P < 0.05). However, the area of intervertebral bone-graft in reformative group [(5.94 +/- 1.17) cm2] was significantly larger than that in traditional group [(4.81+/- 0.97) cm2] at 7 days after operation (t = -6.365, P = 0.000). At 3 and 12 months after operation, the fusion rate was respectively 84.2% and 92.1% in traditional group and was respectively 88.6% and 94.3% in reformative group. Although the height of intervertebral space were increased when compared with preoperative height, the incidence rates of Cages subsidence in traditional group were 44.74% and 47.37% respectively at 3 and 12 months after operation and were significantly higher those that in reformative group (11.43% and 14.29% respectively) (P < 0.05). In addition, the height difference between affected side and normal side in traditional group was significantly larger than that in reformative group (P < 0.05). CONCLUSION: Both single and double Cage implanted into the intervertebral body through unilateral TLIF have good effectiveness. However, double Cage implanted into intervertebral body may hold the height of intervertebral space, reduce the incident rate of Cage subsidence, and prevent sagittal imbalance. PMID- 26875273 TI - [INDUCED MEMBRANCE TECHNIQUE OF HOLLOW POROUS ANTIBIOTIC- IMPREGNATED BONE CEMENT FORMING IN VITRO AND LAVAGE IN VIVO FOR TREATMENT OF OSTEOMYELITIS]. AB - OBJECTIVE: To explore the effectiveness of induced membrane technique of hollow porous antibiotic-impregnated bone cement forming in vitro and lavage in vivo for the treatment of osteomyelitis. METHODS: Between January 2010 and March 2014, 14 cases of osteomyelitis were treated by induced membrane technique of hollow porous antibiotic-impregnated bone cement forming in vitro and lavage in vivo after debridement at the first stage, then the bone cement with bone graft was replaced during the induced membrane after infection was controlled at the second stage. The time from first to second stage operation was 8-12 weeks (average, 10.2 weeks). There were 11 males and 3 females, aged 18 to 69 years (average, 39.2 years). According to Cierny-Mader classification of osteomyelitis, 2 cases were rated as intramedullary type, 5 cases as limited type, and 7 cases as diffusing type. The course of osteomyelitis was 3 months to 20 years, averaged 1.9 years. The healing of bone defect and the functionary recovery of adjacent joint were evaluated according to Paley's method. RESULTS Debridement was performed for two times in 1 case, and for one time in 13 cases for control of bone infection at the first stage. All incisions healed by first intention after second stage. All patients were followed up 15-48 months (average, 13.4 months), with no recurrence of infection. All bone defects healed, and the clinical healing time was 4-5 months (average, 4.4 months). The results of bone healing grade were excellent in all cases at 1 year after operation; the functional recovery of adjacent joint at last follow-up was excellent in 4 cases, good in 8 cases, and fair in 2 cases, and the excellent and good rate was 85.7%. CONCLUSION: Induced membrane technique of hollow porous antibiotic-impregnated bone cement forming in vitro and lavage in vivo for treatment of osteomyelitis has the advantages of high rate of elution of antibiotics, ease of lavage of medullary cavity, and no damage to induced membrane and bony interface between bone and bone cement when removing cement, it is effective for control of bone infection and repair of bone defect. PMID- 26875274 TI - [PLASTIC SURGERY OF SCALP AND FACIAL PLEXIFORM NEUROFIBROMAS]. AB - OBJECTIVE: To explore the plastic surgical treatment and the way to reduce hemorrhage for scalp and facial plexiform neurofibromas. METHODS: Between July 2004 and July 2013, 20 patients with scalp and facial plexiform neurofibromas (17 cases of neurofibromatosis type I and 3 cases of plexiform neurofibroma) were treated, and the clinical data were retrospectively analyzed. There were 9 males and 11 females with an average age of 37 years (range, 18-56 years). The disease duration ranged from 8 to 56 years (mean, 19 years). The scalp was involved in 6 cases, the face in 7 cases, and both the scalp and face in 7 cases. The extent of involvement ranged from 4 cm x 3 cm to 15 cm x 13 cm. Obvious pigmentation was seen in 2 cases. Endovascular embolization was performed before surgical intervention in 4 cases. Preliminary sutures around the lesion were carried out in 18 cases having an involved range over 5 cmx5 cm. One-stage excision was performed in 17 cases, and two-stage excision in 3 cases. Wound repair and facial orthopedic treatment were performed after tumor excision. RESULTS: The intraoperative blood loss was 100-500 mL (mean, 300 mL) for patients undergoing single operation. For 3 patients undergoing two-stage excision, the blood loss of the first operation was 500, 600, and 800 mL respectively, and the blood loss of the second operation was all 50 mL. Autologous blood transfusion of 200, 400, and 400 mL was performed in 3 cases respectively. The preliminary sutures were removed at 3-7 days (mean, 5 days) after operation. All the incisions healed primarily without secondary hemorrhage and hematoma, and the flap and skin graft survived totally. Fifteen patients were followed up 1 year to 7 years (mean, 2.5 years). All patients showed significant improvement in appearance. No significant progression, expanding, and sagging were observed. CONCLUSION: Endovascular embolization and preliminary sutures around the lesion can be used to reduce hemorrhage in resection of plexiform neurofibroma in the scalp and face. Personalized surgical plan of benign neurofibromatosis should be made to reduce the tumor mass, to improve function and appearance. PMID- 26875275 TI - [USE OF ARTIFICIAL BONE OF TRICALCIUM PHOPHATE IN SELLAR FLOOR RECONSTRUCTION AFTER TRANSSPHENOIDAL MICROSURGERY FOR PITUITARY ADEOMA]. AB - OBJECTIVE: To explore the effectiveness of the usage of artificial bone of tricalcium phophate in sellar floor reconstruction after transsphenoidal microsurgery for pituitary adeoma. METHODS: Between January and December 2014, 85 patients with pituitary adema underwent transsphenoidal microsurgery, and the clinical data were retrospectively analyzed. "Sandiwich" was used for sellar floor reconstruction in 46 cases (control group), and "sandiwich" combined with the artificial bone of tricalcium phophate in 39 cases (trial group). There was no significant difference in gender, age, disease duration, size of tumor, invasiveness, and the degree of damage to the sellar floor between 2 groups (P > 0.05). RESULTS: Total removal and subtotal removal of tumors were achieved in 39 cases and 7 cases of the control group, and in 33 cases and 6 cases of the trial group, showing no significant difference between 2 groups (Z = -1.303, P = 0.193). Cerebrospinal leakage occurred in 8 cases of the control group and in 10 cases of the trial group during operation, showing no significant difference (Z = -1.748, P = 0.080). The case number of cerebrospinal leakage in the control group (4 cases) was significantly more than that in the trial group (0) after operation (P = 0.020). The time of gauze removal in the trial group (3 days) was significant shorter than that in the control group [(4.3 +/- 1.6) days] (t = 2.236, P = 0.033). The patients were followed up 3-14 months in the control group and 5-13 months in the trial group. No cerebrospinal leakage occurred during follow-up. CONCLUSION: Sellar floor reconstruction with artificial bone of tricalcium phophate is safe, and it can reduce cerebrospinal leakage and shorten the time of gauze removal. PMID- 26875276 TI - [CLINICAL EXPERIENCE IN DIAGNOSIS AND MANAGEMENT OF COMPLETE DUPLICATION OF KIDNEY AND URETER IN 106 CHILDREN]. AB - OBJECTIVE: To discuss the clinical classification and treatment protocols of complete duplication of kidney and ureter in children. METHODS: Between March 2000 and February 2015, 106 children with complete duplication of kidney and ureter were treated, and the clinical data were retrospectively analyzed. Of them, there were 11 boys and 95 girls, aged from 1 month to 11 years (mean, 3.5 years); one side was involved in 88 cases and two sides in 18 cases. They were divided into 4 types according to image examinations and clinical presentations: 14 patients who needed no special treatment were classified into the first type, 15 patients who underwent reconstruction into the second type, 74 patients who underwent segment removal of renal dysplasia and subtotal excision of abnormal duplicated ureter into the third type, and 3 patients who underwent removal of the whole affected kidney and subtotal excision of whole ureter into the forth type. RESULTS: The patients were followed up 2 months to 14 years (median, 23 months). There was no deteriorating case in the first type. There was no complication such as leakage of urine, discomfort over the back and loins, ureterocele, reproductive tract infection, or hematuresis in the other types. The results of white blood cell count, renal function, and electrolyte presented no abnormality. One patient in the second type and 6 patients in the third type had ureteral stump syndrome; 1 patient in the second type and 3 patients in the third type had urinary tract infection; and 3 patients in the second type had mild hydronephrosis after operation. CONCLUSION: It can obtain good clinical outcome to choose individualized treatment according to clinical classification of complete duplication of kidney and ureter, which can reserve effective renal units as much as possible and improves the patients' quality of life. PMID- 26875277 TI - [REPAIR OF COMPOSITE TISSUE DEFECTS OF DORSAL THUMB INCLUDING INTERPHALANGEAL JOINT BY TRANSPLANTATION OF MODIFIED HALLUX TOE-NAIL COMPOSITE TISSUE FLAP]. AB - OBJECTIVE: To explore a new improved technique and its effectiveness to repair dorsal thumb composite tissue defects including interphalangeal joint by transplantation of modified hallux toe-nail composite tissue flap. METHODS: The hallux toe-nail composite tissue flap carrying distal half hallux proximal phalanx, extensor hallucis longus, and interphalangeal joint capsule were designed and applied to repair the dorsal skin, nails, and interphalangeal joint defect of thumb in 14 cases between January 2007 and June 2013. They were all males, aged from 19 to 52 years (mean, 30 years). The time from injury to hospital was 0.5-2.0 hours (mean, 1.2 hours). The area of the thumb nail and dorsal skin defects ranged from 2.5 cm x 1.5 cm to 5.0 cm x 2.5 cm. The dorsal interphalangeal joint had different degrees of bone defect, with residual bone and joint capsule at the palm side. The length of bone defect ranged from 2.5 to 4.0 cm (mean, 3.4 cm). The hallux nail flap size ranged from 3.0 cm x 2.0 cm to 6.0 cm x 3.0 cm. The donor sites were repaired by skin grafting in 5 cases, and retrograde second dorsal metatarsal artery island flap in 9 cases. RESULTS: After operation, arterial crisis occurred in 1 case and the flap survived after relieving pressure; the other flaps survived, and wounds healed by first intention. Liquefaction necrosis of the skin grafting at donor site occurred in 3 cases, and the other skin grafting and all retrograde second dorsal metatarsal artery island flaps survived. The follow-up ranged from 9 months to 3 years and 6 months (mean, 23 months). The secondary plastic operation was performed in 4 cases at 6 months after operation because of slightly bulky composite tissue flaps. The other composite tissue flaps had good appearance, color, and texture. The growth of the nail was good in 12 cases, and slightly thickened in 2 cases. At last follow-up, X-ray examination showed that bone graft and proximal phalanx of the thumb had good bone healing in 12 cases. Good bone healing was obtained at the donor site. According to the Hand Surgical Branch of Chinese Medical Association standard for thumb and finger reconstruction function, the results were excellent in 12 cases and good in 2 cases, and the excellent and good rate was 100%. No pain at donor site was observed, with normal gait. CONCLUSION: Transplantation of modified hallux toe-nail composite tissue flap to repair dorsal thumb composite tissue defects including interphalangeal joint can effectively improve the appearance and function of the impaired thumb. PMID- 26875278 TI - [LONG-SEGMENTAL TRACHEA REPLACEMENT USING NICKEL-TITANIUM ALLOY STENT WRAPPED WITH AUTOLOGOUS PERICARDIUM]. AB - OBJECTIVE: To perfect the surgical process that trachea could be reconstructed by nickel-titanium (Ni- Ti) alloy stent wrapped with autologous pericardium, and to evaluate the effectiveness and observe the complications. METHODS: In the experiment, twelve healthy Bama suckling pigs with weight of 18-25 kg were selected. The pericardium was harvested to cover the Ni-Ti alloy stent. The compound artificial trachea was used to reconstruct long-segmental (6 cm) trachea defect. The effectiveness, complications, the properties, and growth rate of the new mucosa of the artificial trachea lumen were observed. RESULTS: Of 12 pigs, 2 died soon because of hemorrhage and infection, respectively; 7 died at 2-4 months after operation because of hyperplasia at the middle section and blockage of phlegm plug; 3 survived after 42 weeks postoperatively, but accompanied with dyspnea symptom. At 1, 2, 3, 4, and 5 months after operation, the average crawl length of the new trachea mucosa was 1, 3, 5, 7, and 10 mm, respectively; the occurrence rates of anastomotic stenosis were 0 (0/10), 0 (0/9), 0 (0/4), 33.3% (1/3), and 33.3% (1/3) respectively; and the occurrence rates of scar hyperplasia in the middle of lumen were 20% (2/10), 66.7% (6/9), 75.0% (3/4), 66.7% (2/3), and 100% (3/3), respectively. At 7 months postoperatively, the bronchoscopy examination showed that the scar in central part of artificial trachea had the trends of stagnation, softening, and narrowing, and respiratory symptom had the trend of slight ease. Hyperplasia tissue could be found in central part of artificial trachea by autopsy and was verified to be fiber cells and necrotic tissue by pathology examination. CONCLUSION: Ni-Ti alloy stent with autologous pericardium can insure that the reconstructed tracheal lumen is unobstructed, and support the trachea epithelium regeneration; the main factors of the death of the PMID- 26875279 TI - [EPIDERMAI GROWTH FACTOR SECRETED BY ASTROCYTES STIMULATED WITH TACROLIMUS PROMOTING NEURITE OUTGROWTH]. AB - OBJECTIVE: To illustrate the role of epidermal growth factor (EGF) secreted by astrocytes in the process of tacrolimus (FK506) in promoting neurite outgrowth. METHODS: The spinal cord astrocytes and neuronal cells were isolated respectively from 2-day-old Sprague Dawley (SD) rats and 15-day SD pregnant rats, and cultured in vitro and identified by immunofluorescence staining. The spinal cord astrocytes were cultured with 20 umol/L FK506 medium in the experimental group, and with FK506 free medium in the control group. The supernatant was collected after 24 hours for preparing conditioned medium, and astrocytes were collected. EGF proteins in the conditioned medium were detected with ELISA, and EGF gene expressions of astrocytes were detected with real-time quantitative PCR (RT qPCR). The spinal cord neurons were cultured respectively with conditioned medium from the experimental group (FK506-CM) and the control group (C-CM) in group A and group B, also with neutralized C-CM and neutralized FK506-CM with anti-EGF neutralizing antibodies in group C and group D. Both the total neurite length and the longest neurite length were measured and compared among groups. RESULTS: Both astrocytes and neurons were confirmed by immunofluorescence staining. The EGF content of experimental group (0.241 +/- 0.044) was significantly higher than that of the control group (0.166 +/- 0.014) (t = 3.93, P = 0.01); EGF gene expression of the experimental group (1.12 +/- 0.25) was significantly higher than that of the control group (0.46 +/- 0.11) (t = 5.78, P = 0.00). The neurite length measurement displayed that the total neurite length and the longest neurite length of groups C and D were significantly shorter than those of groups A and B (P < 0.05). Both the total and longest neurite length of group A were significantly longer than those of group B (P < 0.05), but no significant difference was shown between groups C and D (P > 0.05). CONCLUSION: The EGF secreted by spinal cord astrocytes can promote the neurite outgrowth. So spinal cord astrocytes can be used as an important intermediary target of FK506 to promote the recovery of neurological function. PMID- 26875280 TI - [FLUORESCENCE DISTRIBUTION IN BONE AND CARTILAGE TISSUE BY SECTIONING OF FROZEN UNDECALCIFIED BONE]. AB - OBJECTIVE: To introduce a technique of frozen sections for undecalcified bone and discuss its feasiblity by observing the fluorescence distribution of the bone and cartilage. METHODS: The male Sprague Dawley transgenic rats at the age of 8 weeks, which express green fluoreschent protein were selected to isolate the whole knee sectioned by teh undecalicified bone fronze section techynique. Under the fluorescence and light microscopy, the fluorescence and structure were observed within the organization of slice. Immunohistochemical staining (collagen type I and II, He staining, toluidine blue staining, and Alizarin red staining were performed to observe the distribution of fluorescent substance and cartilage and bone structure. RESULTS: The thickness of sections prepared by this technology was 6 um. General observation showed that the structure of secioned joint was complete. Under the light microscope, the morphology of cartilage cells, the arrangement of subchondral bone, and trabecular bone traveling could be clearly distinguished. Under fluorescence microscope, green fluorescence was shonw in the joint soft tissue, cartilage tissue, and bone tissue; collagen type I expressed in the bone tissue, collage type II in cartilage tissue. HE staining and toluidine blue staining could clearly distinguish the morphology of the cartilage layer. Alizarin red staining showed the structural integrity of subchondral bone plate and the organization within the meniscus, and proximal tibia cortical bone continuity. CONCLUSION: The fluorescence distribution can be directly observe in the bone and cartilage by sectioning of frozen undecalcified bone. This new technology can shorten the cycle of preparing sections. PMID- 26875281 TI - [RESEARCH PROGRESS OF KLIPPEL-FEIL SYNDROME WITH EAR MALFORMATION]. AB - OBJECTIVE: To summarize the research progress in clinic, development, and genetics of the Klippel-Feil syndrome and its primary ear deformity. METHODS: The related literature at home and abroad concerning the Klippel-Feil syndrome with ear malformation was reviewed, analyzed, and summarized. RESULTS: The clinical manifestation and classification of Klippel-Feil syndrome are complicated. As one of the most important accompany malformations, ear deformity mainly leads to hearing impairment and abnormal appearance. However, it is still unclear exactly how the ear deformity forms in Klippel-Feil syndrome, and there is little deep study on the internal connection between the ear deformity and other malformations. The premise for the treatment of Klippel-Feil syndrome includes accurate diagnoses and comprehensive disease assessment, and multidisciplinary collaboration will be the important direction of clinical practice in the future. CONCLUSION: Ear malformation is one of the most important congenital dysplasias in the Klippel-Feil syndrome. Its etiology should be based on research in the development and genetic mechanism. And its diagnosis and treatment should be followed by multidisciplinary collaboration. It is important to pay attention to identifying with ear malformation in other syndromes as well. PMID- 26875282 TI - [RESEARCH PROGRESS OF ROLE OF ESTROGEN AND ESTROGEN RECEPTOR ON ONSET AND PROGRESSION OF ADOLESCENT IDIOPATHIC SCOLIOSIS]. AB - OBJECTIVE: To review the recent progress in research on the role of estrogen and estrogen receptor on the onset and progression of adolescent idiopathic scoliosis (AIS). METHODS: The recently published clinical and experimental literature at home and abroad on abnormality of estrogen and its receptor in AIS was reviewed and summarized. RESULTS: There are many abnormal changes of estrogen and estrogen receptor in most AIS patients, including higher serum estrogen concentration, unusual cellular response to estrogen, late age at menarche, and gene polymorphisms of estrogen receptor, which are closely associated with AIS predisposition, curve severity, and scoliosis progression. CONCLUSION: Estrogen and its receptor participate in the onset and progression of AIS by certain mechanisms, but exact mechanism remains indefinite, which needs further research to better define the role of estrogen and its receptor in AIS. PMID- 26875283 TI - [RESEARCH PROGRESS OF AUTOLOGOUS VEIN NERVE CONDUIT FOR REPAIR OF PERIPHERAL NERVE DEFECT]. AB - OBJECTIVE: To summarize the research progress of autologous vein nerve conduit for the repair of peripheral nerve defect. METHODS: The recent domestic and foreign literature concerning autologous vein nerve conduit for repair of peripheral nerve defect was analyzed and summarized. RESULTS: A large number of basic researches and clinical applications show that the effect of autologous venous nerve conduit is close to that of autologous nerve transplantation in repairing short nerve defect, especially the compound nerve conduit has a variety of autologous nerve tissue, cells, and growth factors, etc. CONCLUSION: Autologous vein nerve conduit for repair of non-nerve defect can be a good supplement of autologous nerve graft, improvement of autologous venous catheter to repair peripheral nerve defect is the research direction in the future. PMID- 26875284 TI - [Six Decades in the Service of a Science: The Communicationes de Historia Artis Medicinae]. PMID- 26875285 TI - [Semmelweis Memorial Speech on the 150. Anniversary of His Death]. AB - Two questions emerge as regards Semmelweis's reception and public memory: 1. How and why could turn Semmelweis into an emblematic representative of 19th-20th century science and medicine? 2. What sort of values and ideals does the fate of Semmelweis represent for us? Author calls our attention to the fact, that in Semmelweis's case, not only his discoveries and thought proved to be of abiding value, but during the last 120 years also his fate inspired a number of scientific, popular, non fictional and fictional analysis all over the world. Semmelweis, as a mythic representative of the modern "scientist" still owes a peculiar place in the common memory. His manipulated and partly intentionally coined story--based however on empirical facts--even today represents a relevant message and plays an important role in the making of the myth of modern physician. Author however emphasizes, that Semmelweis myth represent a somewhat different message for the international public and for the Hungarian one. PMID- 26875286 TI - [Ignaz Philipp Semmelweis -- remembrance and assessment of his achievement by the discovery of the causes of puerperal fever, in Austria in the 20th and 21st centuries]. PMID- 26875287 TI - [The growth and spread of the antiseptic method in Italy (Semmelweis, Bottini, Lister)]. PMID- 26875288 TI - [Surviving handwritten signatures of Ignac Semmelweis]. AB - We know only rather few samples of Semmelweis's handwriting and therefore it is important to carefully preserve those we have. The first collection of his manuscripts was published by Antall et al in 1968. During the following 47 years only rather few further samples of his handwriting have been published. Our present collection completes the former list with two previously unknown letters and with an earlier unpublished document signed by Semmelweis. The first document is a certificate written by Semmelweis in 1854 regarding the age of a woman who delivered her child at Szent Rokus Hospital in Pest. The second document includes a request from the Court of Justice towards the Medical Faculty's of the University of Pest regarding the body's opinion in a case of infanticide. The third document is a registration book of a student at the University of Medicine signed by Semmelweis in 1859. Present work attempts to list all of Semmelweis's handwritings known at this moment. The list includes 29 documents written by Semmelweis and further 16 documents signed by him. PMID- 26875289 TI - [Health Policy in the Balkanic States during the 18-19th Centuries]. PMID- 26875291 TI - ERVIN BAUER AND CANCER RESEARCH. PMID- 26875290 TI - [History of Smallpox Vaccination and of the Vaccine Supply in Hungary, up to 1890]. AB - One of the preconditions for the spread of vaccination against pox diseases was making vaccination available. The first vaccinations were carried out using original cowpox lymph sent by Jenner. For further vaccinations the vaccine was extracted from the blisters of those who had been successfully inoculated. In order to provide vaccine continuously six vaccine centres were set up in 1804 in the following cities: Pest, Buda, Kassa, Gyula, Pozsony and Zagrab (Croatia). Detailed information is available only about the centre in Pest which operated in Rokus Hospital under the leadership of the hospital director Andras Bossanyi. Besides regular vaccination they also provided vaccine for the countryside. From 1824 the vaccine was relocated to the medical faculty of the university in Pest and Ferenc Gebhardt, an instructor of surgeons, became its head. The centre operated in the building of the medical faculty and vaccinations were given on Thursdays and Sundays. After the retirement of Gebhardt in 1860, the centre was taken over by the dermatologist Ferenc Poor for a short time, then by Ignac Semmelweis. From 1863 Gergely Patrubany was responsible for managing the centre. In 1874 the central vaccine institution moved to the Hospital for Poor Children in Pest where it was led first by Lazar Wittman, then by Geza Hainiss. In the 1880s private institutions appeared, the best known were Dani Pecsi's centre in Pest and Bela Intze's one in Tirgu Lapus (Romania). Between 1873 an 1889 Andras Kreichel ran a vaccine centre in Nalepkovo (Slovakia). PMID- 26875292 TI - [Life and Work of Pharmacist Bernat Muller]. PMID- 26875293 TI - [Participation of Hungarians in the Elaboration of Principles of Genetics and of Biotehchnology]. AB - It was in 1983 that Robert Bud, director of The Science Museum in London, made it public that the principles of biotechnology, and the term itself were first put into words by a Hungarian scientist, Karoly Ereky (The use of life. A history of biotechnology. Cambridge - New York--Melbourne, Cambridge University Press, 1993). Karoly Ereky stated that if raw material is used to produce consumer goods with the help of living organisms, the workflow data can be collected in biotechnology. He phrased the principles of biotechnology in his book published in German in 1919 called Biotechnology, ranking him among the world's greatest (Verlag Paul Parey, Berlin, 1919). In 1918 in Brno, three years before the birth of Mendel, count Imre Festetics formulated his theses in 4 points in his publication "Die genetische Gesetze der Natur" (Oekonomische Neuigkeiten und Verhandlungen. Brunn, 22: 169-170, 1819), using the word 'genetics' for the first time in the world. It was Vitezslav Orel, director of the Mendel Museum in Brno, who brought the attention of the world to this fact in 1989, based on the documents possessed by the Museum. The English scientist J.R. Wood published his new findings in 2001, accord- ing to which Festetics summarized his results in the form of four genetic laws well before Mendel, describing principles of the process of mutation and inheritance. Festetics provided evidence for the improvement of the stock by cross-breeding. He stated Mendel's second law on the importance of selection. He called attention to the priority of internal genetic fac- tors. Hungarians can rightly be proud of Karoly Ereky (1878-1952) and count Imre Festetics (1764-1847). PMID- 26875294 TI - [Healing Dental and Oral Problems by Remedies of Animal and of Human Origin]. AB - Use of matierials of animal or human origin in dentistry (and generally in medicine) these days is regarded as an unusal way of intervention. However in earlier times, different tissues, parts, products and organs of animals were frequently used in healing. Some of these methods were rooted in magical thinking. As analogical treatments--based on similarity or analogy--e.g. powder of horn or teeth of pike was used for the treatment of decayed teeth and different worms, maggots, veenies were applied against "toothworm". By difficult eruption of primary teeth bone marrow or brain mixed with cockridge-blood and goatmilk was a widely used medicine. Butter and honey were able to help the growing of teeth, as well. Parts of frog (fe: flippers) were also components of curing materials. Egg as the symbol of life was often an ingredient of medicaments. For the treatment of inflamed gum different animal materials were used, like chin and teeth of wolf, pike, crayfish, milk, honey, human saliva etc. Animal or human stools, mucks (containing enzymes) did one's bit in healing of oral and dental illnesses and were applied as fomentation or swathing. Placing a leech on the inflamed face was a common procedure in the past even as the use of earwax in lipnook. In our days tissues, parts or products of animals (or human beings) usually never allowed to get into contact with the body of patients. It's a much safer routine, at the same time however a precious traditional knowledge vanishes forever. PMID- 26875295 TI - [Government Council Professor Karl Semmelweis (1906-1989), regional historian of Burgenland and Semmelweis researcher]. PMID- 26875296 TI - [Dr. Jozsa Daniel (1795-1849)--Daniel Jozsa, MD (1795-1849)]. AB - The present study summarizes the most important events of life and professional career of Daniel Jozsa born 220 years ago. Jozsa, the Medical Chief of former Crasna county was born in Uzon of Szekely region on 1, October, 1795. From the age of 10 he studied at the Bethlen College in Nagyenyed. In 1822 he attended the University of Medical Sciences in Vienna, where he got his doctor's degree in 1828. He wrote his dissertation on the diseases of the female breast. In the same year he settled with his first wife in Szilagysomlyo, Crasna county, where he was appointed Medical Chief of the county by the Transylvanian Governor. He gained great medical reputation being a lively, correct and energetic man with rational medical principles ahead of his time. He took part and held a presentation at the general meeting of the Hungarian physicians and nature researchers in Kolozsvar in 1844. As a result, he was elected associate member by both the Royal Hungarian Natural Science Society and the Royal Medical Association of Budapest. While he successfully fought against the spread of cholera during the epidemics of 1831, 1836 and 1848-49, he regularly took part in the public life of the county. From his first wife he had 6 children, from his second wife he had one child. He died in the village Balyok in Bihar county on 10, April, 1849. His tomb has been saved for future generations by the generosity of the local Reformed Church and of some doctors from Balyok. PMID- 26875297 TI - [Mor Karolyi was born 150 years ago]. AB - Dr. Mor Karolyi was born in Szentes (County Csongrad, South-East Hungary) in 1865 in a Jewish family. His original name was Moric Czukkermann--the name was changed to Mor Karolyi in 1883. Karolyi got his medical degree in 1889 at the Budapest Medical University. During his studies he was the student of Jozsef Arkovy, the founder of the Hungarian scientific dentistry. Karolyi later practised in Vienna from 1893 up to 1938. His main lines were the etiology of the diseases of the parodontal area and prosthetics. Thanks to his special method of treating traumatic parodontal diseases he made an international reputation. In 1932 he won the membership of the International Academy of Odontology (Buenos Aires). One of his etiological discoveries is still called Karolyi-effect in international terminology. After the so called Anschluss, Karolyi had to escape from Vienna. In 1938 he settled back to his native city, Szentes. In 1944, being a Jew he was first internated, then deported to Theresienstadt. He died a few days after the liberation of the camp, 17th May 1945. PMID- 26875298 TI - AMBULANCE STATION IN CONSTANTINOPLE. PMID- 26875299 TI - Genetic profile of Mycobacterium tuberculosis and treatment outcomes in human pulmonary tuberculosis in Tanzania. AB - Information on the different spoligotype families of Mycobacterium tuberculosis in Tanzania is limited, and where available, restricted to small geographical areas. This article describes the genetic profile of M tuberculosis across Tanzania and suggests how spoligotype families might affect drug resistance and treatment outcomes for smear positive pulmonary tuberculosis patients in Tanzania. We conducted the study from 2006 to 2008, and the isolates were obtained from samples collected under the routine drug resistance surveillance system. The isolates were from specimens collected from 2001 to 2007, and stored at the Central and Reference Tuberculosis Laboratory. A total of 487 isolates from 23 regions in the country were spoligotyped. We were able to retrieve clinical information for 446 isolates only. Out of the 487 isolates spoligotyped, 195(40.0%) belonged to the Central Asian (CAS) family, 84 (17.5%) to the Latin American Mediterranean (LAM) family, 49 (10.1%) to the East-African Indian (EAI) family, and 33 (6.8%) to the Beijing family. Other isolates included 1 (0.2%) for H37Rv, 10 (2.1%) for Haarlem, 4 (0.8%) for S family, 58 (11.9%) for T family and 52 (10.7%) for unclassified. No spoligotype patterns were consistent with M bovis. Regarding treatment outcomes, the cure rate was 80% with no significant variation among the spoligotype families. The overall level of MDR TB was 2.5% (3/12 1), with no significant difference among the spoligotype families. All Beijing strains (11.8%, 30/254) originated from the Eastern and Southern zones of the country, of which 80% were from Dar es Salaam. Isolates from the CAS and T families were reported disproportionately from the Eastern-Southern zone, and EAI and LAM families from the Northern-Lake zones but the difference was not statistically significant. Five isolates were identified as non-tuberculous Mycobacteria. In conclusion, M. tuberculosis isolates from pulmonary tuberculosis cases in Tanzania were classified mostly within the CAS, LAM, and EAI and T families, while the Beijing family comprised about 7% isolates only. Consistently good treatment outcomes were recorded across these spoligotype families. The proportion of drug resistance strains was low. The findings also suggest variation of spoligotype families with varying geographical localities within the country, and identify this area for further research to confirm this finding. PMID- 26875300 TI - Efficacy of a low-dose ferric-EDTA in reducing iron deficiency anaemia among underfive children living in malaria-holoendemic district of Mvomero, Tanzania. AB - Iron deficiency anaemia is a public health problem in Tanzania especially among children under the age of five years. In malaria holoendemic areas, control of anaemia by supplementation with iron has been reported to increase serious adverse events. The World Health Organization recommends that, programs to control anaemia in such areas should go concurrently with malaria control programmes. The objectives of the study were to: (i) to determine if a supplement providing 2.5 mg of iron as ferric EDTA and 2.5 mg of iron as ferrous lactate (low dose) is as effective in correcting anaemia as a supplement providing the standard 10 mg of iron as ferrous lactate (high dose); and ii) determine if iron supplementation increased the risk of malaria. This study was carried out in Mvomero District of east-central Tanzania. Two groups (69 and 70 subjects per treatment) of moderately anaemic children (7.0-9.1 g of Hb/dl), received one of the two micronutrient supplements differing only in iron content for a period of 60 days. Results showed that, the average haemoglobin (Hb) concentration improved from 8.30 +/- 0.60 g/dl to 11.08 +/- 1.25 g/dl. The average weight-for-age for all children increased from 16.0 to 20.6% while their weight-for-height increased from 4.0 to 13.3%. The incidence of asymptomatic and symptomatic malaria ranged from 10.0 to 10.4% at all time points with no apparent increase in malaria severity due to iron supplementation. Overall, there was a significant reduction in anaemia during the 60 day supplementation period. This study demonstrated that, micronutrient supplements containing low-dose ferric-EDTA is just as effective as the high dose iron in reducing anaemia and can be safely utilized in malaria holoendemic areas to control iron deficiency anaemia. It is recommended that, a large study should be conducted to affirm the effectiveness of the low dose ferric-EDTA in controlling iron deficiency anaemia among underfive children. PMID- 26875301 TI - Providing anti-retroviral therapy in the context of self-perceived stigma: a mixed methods study from Tanzania. AB - Adherence to anti-retroviral treatment (ART) has been a significant step towards improving quality of life among people living with HIV. However, stigma has been described to influence adherence to ART. A cross-sectional mixed methods study was conducted to explore factors related to stigma and perceived influence of stigma on adherence to treatment amongst ART-prescribed patients and health care providers, respectively in Tanzania. Stigma was assessed through interviewer administered survey among 295 patients. The results from patients showed that 279/295 (95%) were satisfied with the services provided at the Care and Treatment Centres (CTCs). The set up of CTCs 107/295 (36%), and queuing at the CTCs 88/295 (30%) were associated with stigma (P < 0.001). The perceived influence of stigma on adherence to ART was assessed using focus group discussions (FGDs) of 33 health care providers (HCPs). Through FGDs, HCPs perceived the set up of CTCs as friendly yet violated confidentiality. The HCPs reported that ART-prescribed patients hide identifiable cards to avoid being recognised by other people. Some patients were reported to rush to avoid familiar faces, and due to the rush they picked wrong medicines. Also some patients were reported to throw away manufacturers' box with dosage instructions written on the box, resulting in use of doses contrary to the prescriptions. We conclude that despite the fact that most patients were satisfied with the services provided at the CTCs, it is important that HCPs provide dosage instructions on another piece of paper or use disposable bags. A common dispensing window for all patients regardless of the diagnosis may be useful to minimize stigma. Also HCPs may introduce appointment system to avoid long queue at the CTCs. PMID- 26875302 TI - Prevalence and awareness of type 2 diabetes mellitus among adult population in Mwanza city, Tanzania. AB - Type 2 diabetes mellitus (T2DM) prevalence is increasing rapidly around the world. This cross-sectional study was conducted to assess the prevalence and awareness of type 2 diabetes mellitus in Mwanza city, Tanzania. A multistage random sampling technique was used to obtain representative subjects. Information about causes and risk factors were collected using structured questionnaire. In addition, community random blood glucose testing was employed to identify those at risk. Subjects with >= 200 mg/dl on the following day were subjected to fasting blood glucose testing and they were confirmed to have T2DM if they had blood glucose level of >= 126 mg/ dl. In each subject, height, weight, waist and hip circumferences and total fat and fat free mass were measured using standard procedures. A total of 640 participants were included in this study, 55% were females and 45% were males. Mean age of the respondent was 43.84 +/- 10.80 years. Most (46.4%) respondents were in the age group 30-40 years. Mean age for females was 44.0 +/- 10.31 years while for males was 43.6 +/- 11.3 years (Table 1). Overall prevalence of T2DM was 11.9%, (n = 76). Prevalence was high in females (7.2%; n = 46) than in males (4.7%; n = 30). The age between 41-50 years had the highest prevalence of T2DM 28.6% followed by 51-60 years age group (17.2%). Significant independent associations were found for age (OR 3.88, 95% CI: 2.16 6.95) positive first degree relative with T2DM (OR 1.34; 95% C: 1.10-1.64) alcohol intake (OR 1.23; 95% CI: 1.02-1.48,) smoking (OR 3.86; 95% CI: 2.57-5.78) and hypertension (OR 0.096; 95% CI: 1.954-18.251). Only 49.2 (n = 315) of the respondents knew about the causes and symptoms of T2DM. Public education on T2DM should be emphasized and routine measurement of blood glucose levels is recommended among adults. PMID- 26875303 TI - Knowledge of diabetes and hypertension among members of teaching staff of higher learning institutions in Dar es Salaam, Tanzania. AB - Diabetes and hypertension are among the most common non-communicable diseases (NCD) that contribute to a large number of adult morbidity and mortality. The objective of this study was to determine knowledge of diabetes and hypertension and the associated risk factors among members of teaching staff of Higher Learning Institutions in Dar es Salaam, Tanzania. A cross sectional community based study was conducted in 10 higher learning institutions including universities. A structured pretested questionnaire was utilized. A total of 139 participants were involved in this study. A total of 139 teaching members of staff from higher learning institutions participated in the study. The majority (74.8%; n=104) of the participants were males. Mean age of the participants was 40.7 +/- 12.6. Over half (56.8%; 79/139) of the respondents correctly identified failure of body to use insulin as one of the causes of diabetes. Of the respondents, 43.2% (60/139) were able to identified heredity as cause of hypertension. Increasing age was correctly identified as one of risk factors for diabetes by 38.1% (53/139) and for hypertension by 36.7% (51/139) respondents. Thus knowledge of the causes, signs and symptoms, risk factors and complications was not as high as expected considering the respondents were among the highly educated and professional population. In conclusion, the majority of teaching staff in the higher learning Institutions in Dar es Salaam were aware of the diabetes and hypertension. However the knowledge of the causes, signs and symptoms, risk factors and complications was not as high as expected. It is important that this group of professionals is appropriately informed as regards to diabetes, hypertension and other non-communicable diseases as they may serve as key advocacy group to the community and policy makers in Tanzania. PMID- 26875304 TI - Addressing the human resource for health crisis in Tanzania: the lost in transition syndrome. AB - Tanzania is experiencing a serious Human Resource for Health (HRH) crisis. Shortages are 87.5% and 67% in private and public hospitals, respectively. Mal distribution and brain drain compound the shortage. The objective of this study was to improve knowledge on the HRH status in Tanzania by analyzing what happens to the number of medical doctors (MD) and doctor of dental surgery (DDS) degree graduates during the transition period from graduation, internship to appointment. We analyzed secondary data to get the number of MDs and DDS; who graduated from 2001 to 2010, the number registered for internship from 2005 to 2010 and the number allowed for recruitment by government permits from 2006 to 2010. Self administered questionnaires were provided to 91 MDs and DDS who were pursuing postgraduate studies at Muhimbili University of Health and Allied Sciences during this study who went through the graduation-internship-appointment (GIA) period to get the insight of the challenges surrounding the MDs and DDS during the GIA period. From 2001 to 2010 a total of 2,248 medical doctors and 198 dental surgeons graduated from five local training institutions and abroad. From 2005 to 2010 a total of 1691 (97.13%) and 186 (126.53%) of all graduates in MD and DDS, respectively, registered for internship. The 2007/2008 recruitment permit allowed only 37.7% (80/218) and 25.0% (7/27) of the MDs and DDS graduated in 2006, respectively. The 2009/20 10 recruitment permit allowed 265 MDs (85.48%) out of 310 graduates of 2008. In 2010/2011 permission for MDs was 57.58% (190/ 330) of graduates of 2009 and in 2011/2012 permission for MDs was for 61.03% ((249/408) graduates of 2010. From this analysis the recruitment permits in 2007/2008, 2009/2010, 2010/2011 1nd 2011/2012 could not offer permission for employment of 482 (38.10%) of all MDs graduated in the subsequent years. Major challenges associated with the GIA period included place of accommodation, allowance (for internship) or salary delay (for first appointment), difficulty working environment, limited carrier opportunities and concern for job security. The failure to enforce mandatory registration for internship and failure to absorb all produced MDs and DDS results to loss of a substantial number of these graduates during the graduation-internship-appointment period. To solve this problem, it is recommended to establish better human resource for health management system. PMID- 26875305 TI - Leptospira infections in freshwater fish in Morogoro Tanzania: a hidden public health threat. AB - Leptospirosis caused by spirochete bacterium of genus Leptospira affects humans and animals worldwide. Rodents are major reservoirs of leptospires whereas wetland and aquatic migratory birds also carry and transmit leptospires. Leptospirosis studies in fish are lacking in African countries despite favourable environment and abundant reservoirs, which can spread leptospires into aquatic habitats and infect fish. The objectives of this study were to determine presence of Leptospira in fish; the prevalent Leptospira serovars and whether are related to serovars reported in animals; and to ascertain potential public health risk. Live tilapia, catfish and eel fish (n = 48) were caught in Mindu Dam in Morogoro Municipality in eastern Tanzania. Blood sample was collected using syringes and needles to obtain serum for serological detection of leptospirosis using gold standard microagglutination test utilizing local and reference Leptospira serovars Sokoine, Kenya, Pomona and Hebdomadis. Twenty-six fish (54.2%) were positive for serovar Kenya (29.2%) and Sokoine (25%). Leptospira prevalence was high in both catfish (58.3%) and tilapia fish (47.8%). Thus, different fish types are infected with Leptospira found in animals. Fish could be source of Leptospira infection to humans since tilapia and catfish are the common fish type widely consumed in Tanzania. Further study covering lakes, rivers and dams is required to better understand the prevalence of Leptospira in fish and actual public health threats. PMID- 26875306 TI - Barriers to men who have sex with men attending HIV related health services in Dar es Salaam, Tanzania. AB - The HIV/AIDS disease burden is disproportionately high among men who have sex with men (MSM) worldwide. If this group will continue to be ignored they will continue to be the focus of HIV infection to the general population. This study explored barriers impeding MSM utilizing the HIV related health services currently available. The objectives of the study were to: (i) determine how stigma and discrimination affect MSM attendance to HIV related health services; (ii) determine how health care worker's (HCW's) practices and attitudes towards MSM affect their attendance to HIV related health service; (iii) learn MSM's perception towards seeking HIV related health services and other factors affecting accessibility of HIV related health services among MSM in Dar es Salaam, Tanzania. This was a descriptive study whereby qualitative methods were employed, using in-depth interviews for 50 individuals and focus group discussions for 5 groups which were conducted at PASADA premises, in Temeke district in 2012. After transcription data was read through, codes created were then collapsed into themes which were interpreted. The findings of this study show that majority of the study participants access HIV related health services in Dar es Salaam when they need to. However, they reported stigma and discrimination, lack of confidentiality and privacy, lack of availability and MSM friendly HIV related health services, financial challenges, poor practices and negative attitudes directed towards them by health workers, fears and lack of HIV knowledge among them as barriers for them to access these services. With these findings, there is an importance of enabling MSM to overcome the perceived stigma when seeking for HIV related health services. Also there is a need to conduct further research with regards to how HCW's treat this group and their understanding on same sex practices. PMID- 26875307 TI - Thirty years old lady with nephrotic syndrome: a case of biopsy proven lupus nephritis in Tanzania. AB - We describe a case of a 30 years old female patient who presented with nephrotic syndrome and impaired renal function diagnosed to have systemic lupus erythematosus (SLE). This is the first biopsy proven lupus nephritis in Tanzania. SLE is common among females and is reported be more common among Africans as compared to other races. This patient presented with nephrotic syndrome, pleural effusion and pericardial effusion which depicts the multisystem effects of SLE. This patient was treated with cyclophosphamide in combination with steroid as induction therapy and attained remission after a month of treatment. Systemic lupus erythematosus should be considered in patients with nephrotic syndrome and these patients should have renal biopsy to determine renal involvement. PMID- 26875308 TI - Bromodeoxyuridine immunofluoresence and differential interference contrast imaging combination can precisely segregate adherent monolayer cells into specific cell-cycle phases. AB - Most cellular-level cancer studies involve the identification of the cell cycle phases in which individual cells are progressing through. Traditional methods such as Fluorescent Activated Cell Sorting (FACS) require several treatments before harvesting the cells-procedures which alter cellular architecture. This study describes a novel method of the cell cycle analysis that preserves the cellular morphology and architecture with minimal in situ milieu perturbation. Primary rat skin fibroblasts were isolated and cultured at standard conditions. The cells were stained with anti-BrdU and examined with LSM 510 laser scanning microscopy. S-phase cells incorporated BrdU while M-phase appeared smaller and spherical. Damaged cells also tended to round-off in shape but, unlike M-phase cells, they did not bind anti-Phospho H3 antibody. G1 and G2 phases did not incorporate BrdU or Phospho H3. The two gap phases were differentiated on the basis of their sizes and subtleties in their shapes. The method is technically simple and less time-consuming while preserving the cellular in situ architecture. Due to its simplicity and accuracy the technique can be easily employed in resource-limited laboratories. Further studies are needed to verify the usefulness of the technique in clinical diagnostics such as cancer biomarkers. PMID- 26875310 TI - Improve cyber security and protect practice finances. PMID- 26875309 TI - ["Epistemic Negotiations" and the Pluralism of the Radiation Protection Regime: The Determination of Radiation Protection Standards for the General Population in the Early Years After World War II]. AB - Radiation protection standards for the general population have constituted one of the most controversial subjects in the history of atomic energy uses. This paper reexamines the process in which the first such standards evolved in the early postwar period. While the existing literature has emphasized a "collusion" between the standard-setters and users, the paper seeks to examine the horizontal relationship among the standard-setters. It first examines a series of expert consultations between the United States and the United Kingdom. Representing a different configuration of power and interest, the two failed to agree on the assessment of genetic damage and cancer induction whose occurrence might have no threshold and therefore be dependent on the population size. This stalemate prevented the International Commission on Radiological Protection (ICRP), established in 1950, from formulating separate guidelines for the general public. Situations radically changed when the Bikini incident in 1954 led to the creation of more scientific panels. One such panel under the U.S. Academy of Sciences enabled the geneticists to bridge their internal divide, unanimously naming 100 mSv as the genetically permissible dose for the general population. Not to be outdone, ICRP publicized its own guidelines for the same purpose. The case examined in this paper shows that the standard-setting process is best understood as a series of "epistemic negotiations" among and within the standard-setters, whose agendas were determined from the outset but whose outcomes were not. PMID- 26875311 TI - Top 10 Challenges Facing Physician in 2016. PMID- 26875312 TI - How relationship marketing can add value to your practice. PMID- 26875313 TI - Legal and ethical considerations for managing your online reputation. PMID- 26875314 TI - Making EHR alerts work for your practice. PMID- 26875315 TI - The covenant. PMID- 26875316 TI - Will 21st Century Cures Act harm patient safety? PMID- 26875317 TI - Hospitals launch specialty pharmacies to curb drug costs. PMID- 26875318 TI - States hold key role in big insurer mergers. PMID- 26875319 TI - Wisconsin systems are leaders in offering their own health plans. PMID- 26875320 TI - Providers struggle on CMS measures. PMID- 26875321 TI - Pre-existing conditions contribute to rising U.S. maternal mortality rates. PMID- 26875322 TI - Herding hospital docs. Staffing firms buy MD groups to strengthen rate clout. PMID- 26875323 TI - Policing the ethics police. Research review boards face scrutiny as feds propose new rules. PMID- 26875324 TI - Nurses turn to speech-recognition software to speed documentation. PMID- 26875325 TI - Why Congress must deal with drug prices. PMID- 26875326 TI - Behavioral-health organizations can partner with hospitals to reduce readmissions. PMID- 26875327 TI - Helping docs cope with federal reforms. PMID- 26875328 TI - Pharma 'could have done a better job' explaining drug costs. PMID- 26875329 TI - Hospital CEO turnover rate by state. Ranked by turnover percentage in 2014. PMID- 26875330 TI - Patient records: the struggle for ownership. PMID- 26875331 TI - Telehealth: the balance between access and ethics. PMID- 26875332 TI - Become a master planner and elevate your practice. PMID- 26875333 TI - Medical marijuana: Legal considerations for physicians. PMID- 26875334 TI - Budgeting for retirement: make a plan and stick to it. PMID- 26875335 TI - Tech tools to aid with revenue cycle management. PMID- 26875336 TI - Wearables: A healthcare fad or revolution? PMID- 26875337 TI - Medical records: creation vs. control. PMID- 26875338 TI - Gun-violence reduction must be treated like auto-safety movement. PMID- 26875339 TI - Major-player health systems look to broaden telehealth's bandwidth. PMID- 26875340 TI - Pfizer-Allergan deal could reduce biosimilar cost savings. PMID- 26875341 TI - ACA delivers expected spending jolt, but long-term cost growth uncertain. PMID- 26875343 TI - company doctoring. More employers offer on-site clinics to reduce workers' health costs. PMID- 26875342 TI - REPRICING HEALTHCARE: HOSPITALS SCRUTINIZE COSTS AS PATIENTS GROW MORE PRICE SENSITIVE. PMID- 26875345 TI - Intelligence sharing, collaboration essential to eliminate cyberthreats in healthcare. PMID- 26875344 TI - Tackle gun violence like other public health problems. PMID- 26875346 TI - Bedside handoffs boost patient satisfaction. PMID- 26875347 TI - Baltimore's recent violence a 'call to action' to address health disparities. PMID- 26875348 TI - Hospitals with best, worst 30-day readmission rates. Ranked by percentage readmitted within 30 days. PMID- 26875351 TI - THE DOCTOR WILL SEE YOU (AND YOUR DATA) NOW. PMID- 26875350 TI - CONTAGION CURTAILED. Can you stop disease with smart devices? PMID- 26875349 TI - The first genetically altered animal is approved for eating. PMID- 26875352 TI - For GOOD. THE BEST INVENTIONS MAKING THE WORLD BETTER. PMID- 26875353 TI - As third open enrollment arrives, the ACA enters its penalty phase. PMID- 26875354 TI - Budget deal could deter hospitals from buying surgery centers. PMID- 26875355 TI - Experts are skeptical value-based purchasing program is helping to boost quality. PMID- 26875356 TI - Medicaid programs brace for new home health wage rule. PMID- 26875357 TI - BOHAN's 'brand villages' work to create captivating stories. PMID- 26875358 TI - The communicator. PMID- 26875359 TI - Marketers reshape ad strategies. PMID- 26875360 TI - Anti-vaping ads show the power of the asterisk. PMID- 26875361 TI - Medicaid losses lead the pack. PMID- 26875362 TI - Advertising diversity. PMID- 26875363 TI - HealthCare.gov 3.0, behaviorally speaking. PMID- 26875364 TI - Quality gains, cost reductions make strong case for the modern house call. PMID- 26875365 TI - Helping tell a story through data. PMID- 26875366 TI - 'People need convincing there's something you can do about climate change'. PMID- 26875367 TI - Largest patient-satisfaction measurement firms. Ranked by total number of clients in 2014. PMID- 26875368 TI - Millennials in Medicine. PMID- 26875369 TI - Building patient relationships through your staff. PMID- 26875370 TI - Don't skimp on your HIPAA risk assessment. PMID- 26875371 TI - Cutting costs to help your practice thrive. PMID- 26875372 TI - Analyze EHR data to improve financial reporting. PMID- 26875373 TI - After the ICD-10 transition: Your questions answered. PMID- 26875374 TI - The payer merger effect: What it means for physicians. PMID- 26875375 TI - Expanded insurance access: its affect on physicians. PMID- 26875376 TI - Congress is final hurdle in removing EHR 'gag clauses'. PMID- 26875377 TI - HOW I DID IT....THE CEO OF ATHENAHEALTH on ON THE ROLE OF ANGER IN STARTING NEW BUSINESSES. AB - As a boy, Bush watched Emergency! on television and was captivated by the romance and seeming magic of saving lives. As an adult, he found the reality of medicine to be very different: There wasn't much humanity in the way health care was actually delivered. Believing that he'd be daunted by the course work required for a medical degree, he decided to take an entrepreneurial route to improving the system. His first sense of the opportunity came while he was driving an ambulance in New Orleans one summer during college. Some patients with chronic disease who couldn't afford their medicines would repeatedly call the ambulance to take them to a hospital where they could be stabilized. What if the ambulance itself were outfitted with treatments for the five most common chronic diseases and carried EMTs who were trained to use them? Those patients could be treated in place, at a radically lower cost than what the hospital would charge. That idea didn't work out, and Bush moved on to think about a network of maternity clinics. He and Todd Park drew up a business plan at Harvard Business School--one that was "unbelievably complicated to execute and very risky." But in the process of pursuing it, they created websites for the paperwork with rules that prevented mistakes. That was the seed for athenahealth, which today supports electronic medical records and a suite of practice management and care coordination services, leaving doctors free to spend more time with their patients. PMID- 26875379 TI - Breast cancer's race problem. PMID- 26875378 TI - What a daily glass of wine does over time. PMID- 26875380 TI - Not all screen time is a no-no for infants. PMID- 26875381 TI - We count pitches to save arms. It's time to track hits to save lives. PMID- 26875382 TI - China's growing deadly addiction. PMID- 26875383 TI - Mammogram guidance gets an overhaul--again. PMID- 26875384 TI - ON ENGAGING WITH SMEs. The NHS can contribute to growing local wealth. PMID- 26875385 TI - RISK TAKING NEEDS TO BE ASSESSED. PMID- 26875386 TI - WE NEED NEW INTERMEDIATE CARE SOLUTIONS. PMID- 26875387 TI - WORKFORCE. HOW TO REDUCE TEMP STAFF. PMID- 26875388 TI - INNOVATION. HSJ launches the Women Leaders network. PMID- 26875389 TI - PROCUREMENT. 'THE NURSES LOVED IT'. PMID- 26875390 TI - Should your blood pressure be way lower than it is? PMID- 26875391 TI - New hope for the treatment and prevention of Alzheimer's. PMID- 26875392 TI - MedAssets deal could pave way for regional, provider-led GPOs. PMID- 26875394 TI - Consumers face many plan changes on the insurance exchanges for 2016. PMID- 26875393 TI - ACA opponents boosted by Kentucky, Virginia elections. PMID- 26875395 TI - Honing cardiovascular care. Truven's top 50 cardiovascular hospitals use data to drive improvements. PMID- 26875396 TI - Outsourcing medical staffing. Hospitals turn to managed-service providers to handle all temporary staffing chores. PMID- 26875397 TI - A green light for attacking Obamacare. PMID- 26875398 TI - Hospitals must address housing in treating the homeless. PMID- 26875399 TI - Nursing home reduces antibiotic use. PMID- 26875400 TI - There's a risk that value-based payment 'is more lip service than the real thing'. PMID- 26875401 TI - Largest U.S. Veterans Affairs hospitals. Ranked by number of total operating beds in fiscal 2014. PMID- 26875402 TI - ELECTRIFY YOUR MIND. PMID- 26875403 TI - Why (almost) everyone is embracing the digital doctor. PMID- 26875404 TI - THE WAR ON DELICIOUS. PMID- 26875405 TI - The New Food Rules. A SIMPLER, SANER WAY TO EAT IS HERE. PMID- 26875406 TI - The science of why people 'snap' in anger. PMID- 26875407 TI - The Diet Prescription. PMID- 26875408 TI - DIAGNOSTICS. TESTING TIMES. PMID- 26875409 TI - DIAGNOSTICS: CASE STUDIES. SO HOW EFFICIENT ARE YOU? PMID- 26875410 TI - PARTNERSHIPS. CAN I WATCH NETFLIX? PMID- 26875411 TI - ON THE JUNIOR DOCTORS CONTRACT. Ministers can't spin out of the contract standoff. PMID- 26875412 TI - CIRCLE'S BEDFORD CONTRACT IS FAR FROM PERFECT. PMID- 26875413 TI - AVOIDABLE HARM LACKS A STRATEGY. PMID- 26875414 TI - Legal. Seven day care can save money. PMID- 26875415 TI - INNOVATION. SMALL STEPS, GIANT LEAPS. PMID- 26875417 TI - WHY THE NHS NEEDS A SHARED STRATEGY. PMID- 26875416 TI - ON THE ROLE OF MERGERS IN THE NHS. Mergers should be the exception, not the rule. PMID- 26875418 TI - EMPLOY PEOPLE WITH DISABILITIES. PMID- 26875419 TI - SERVICE IMPROVEMENT. EVIDENCE WE CAN ALL USE. PMID- 26875420 TI - DIABETES CARE. THINK ON YOUR FEET. PMID- 26875421 TI - SERVICE IMPROVEMENT. IT'S TIME TO HEAL. PMID- 26875422 TI - MENTAL HEALTH. INTEGRATING ALL PARTNERS. PMID- 26875423 TI - COMMUNITY SERVICES. Work together to cut alcohol related hospital admissions. PMID- 26875424 TI - Integration is a question of balance. PMID- 26875426 TI - Sevoflurane and thiopental preconditioning attenuates the migration and activity of MMP-2 in U87MG glioma cells. AB - BACKGROUND: Tumor cell migration and diffuse infiltration into brain parenchyma are known causes of recurrence after treatment in glioblastoma (GBM), mediated in part by the interaction of glioma cells with the extracellular matrix, followed by degradation of matrix by tumor cell derived proteases, particularly the matrix metalloproteinases (MMP). Sevoflurane and thiopental are anesthetics commonly used in cancer surgery. However, their effect on the progression of glioma cells remains unclear. The aim of this study was to explore the role of these anesthetics on the migration and activity of MMP-2 in glioma cells. METHODOLOGY: Cultured U87MG cells were pretreated with sevoflurane or thiopental and in vitro wound healing scratch assay was carried out to analyze their effect on migration of these cells. Gelatin zymography was carried out to examine the effect of these anesthetics on tumor cell MMP-2 activity using the conditioned media 24 h after pretreatment. Cell viability was analyzed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. RESULTS: U87MG cells exposed to 2.5% sevoflurane or different concentrations of thiopental significantly decreased migration and activity of MMP-2 compared to control. No effect was seen on the viability of these cells after pretreatment with sevoflurane or thiopental. CONCLUSION/SIGNIFICANCE: These results suggest that both sevoflurane and thiopental have inhibitory effect on the migration and MMP-2 activity in glioma cells. Thus, it is important that the choice of anesthetics to be used during glioma surgery takes into account their inhibitory properties against the tumor cells. PMID- 26875427 TI - Preservation and Microsurgical Repair of the Superficial Temporal Artery During Pterional Craniotomy. AB - OBJECTIVE: To study the rate of superficial temporal artery (STA) preservation and the effectiveness of STA reconstruction in patients undergoing a pterional craniotomy. METHODS: Included patients (n = 136) underwent either an emergency or an elective pterional craniotomy. In case of deliberate transection or accidental damage of the STA, it was repaired microsurgically at the end of the procedure. Postoperatively, the patency of the STA was assessed on CT angiography, MR angiography, or conventional angiography and complications related to wound healing were recorded. RESULTS: Of the 136 operated patients, the STA could be identified in 120 cases (88%). Of these 120 cases, the STA could be dissected and left undamaged in 60 patients (44%). In 52 patients (38%), 1 of the 2 branches of the STA had to be transsected to elevate the muscle-skin flap. Forty-six of the transected arteries could be anastomosed at the end of the procedure. All of these arteries were patent directly after repair. In the remaining 16 patients (12%), the STA was not identified during approach. All anastomosed arteries (n = 46) were patent. Two patients developed a postoperative infection. CONCLUSIONS: Preserving or reconstructing of the STA during pterional craniotomy is feasible in the majority of the patients with very high rate of anastomosis patency. STA hinders elevation of the skin/muscle flap in approximately 38% of the pterional approaches and without reconstruction afterwards, the STA would been occluded. PMID- 26875428 TI - Heart rate-guided, but not dose-guided titration of beta blockers stabilizes ventricular repolarization in patients with chronic heart failure. AB - AIMS: We compared the effects of heart rate-guided and dose-guided beta-blocker titration strategies on QT variability in patients with chronic heart failure (CHF). METHODS: In a prospective study we recorded 5-minute resting high resolution ECGs (HRECG) in 100 patients with CHF and measured heart rate (HR) and ventricular repolarization by QT variability index (QTVI). In a subgroup of patients not reaching target HR (<70bpm) we uptitrated beta blockers and repeated HRECG measurements 3months thereafter. RESULTS: Target HR was present in 46 patients (group A), and in 54 patients HR was above target (group B). The groups did not differ in age, gender, NYHA class, NT pro-BNP, creatinine, or beta blocker dose. Patients in group A displayed significantly lower QTVI than patients in group B (-1.25+/-0.55 vs. -1.52+/-0.42, P=0.013). When uptitrating beta-blockers we found a decrease in HR (from 91+/-15bpm to 71+/-15bpm, P<0.001), NTpro BNP levels (from 4474+/-3878pg/ml to 3042+/-2566pg/ml, P=0.024), and NYHA class (from 3.0+/-0.8 to 2.5+/-0.7, P=0.006). With beta-blocker uptitration QTVI decreased in 10 of 24 patients (42%). In these patients HR decreased more than in the remaining cohort (-25+/-20bpm vs. -15+/-17bpm, P=0.017). On multivariate analysis, the presence of target HR was a predictor of QTVI decrease (P=0.017), but beta-blocker dose was not. CONCLUSIONS: In patients with CHF treated by beta blockers, changes in QT variability appear to occur in parallel with changes of heart rate. This suggests that heart rate-guided titration of beta-blockers may be associated with decreased risk of sudden cardiac death. PMID- 26875429 TI - [Pathophysiology of inflammation]. AB - Inflammation results from activation of the immune system in response to a broad range of different stimuli. The immune system is a highly complex and evolutionary optimized defense system with cellular and humoral components. The course of an inflammatory response is influenced by the immune condition of the host, the virulence e. g. of an infectious agent, and the fine tuning of the local tissue reaction, which may be influenced by individual genetic factors. Immunity is a compromise between insufficient (immunodeficiency) or exaggerated (autoimmunity) immune reactions. The dynamic balance between these two extremes is achieved through stringent T- and B-cell selection in the bone marrow and thymus on the one hand and through "checkpoint control" in peripheral lymphatic tissues. Many tumors have ways to suppress local immune responses and to escape destruction through the immune system (one of the so-called "hallmarks of cancer"). In recent years, different approaches have successfully been able to reverse this local immunosuppression. First clinical trials using these strategies have shown highly promising results indicating that the therapeutic use of the immune system will be a very effective instrument in the arsenal of cancer treatment agents. PMID- 26875430 TI - Prognostic significance of volume-based 18F-FDG PET/CT parameter in patients with surgically resected non-small cell lung cancer. Comparison with immunohistochemical biomarkers. AB - AIM: We investigated the prognostic value of volume-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) parameters compared with other factors including several immunohistochemical biomarkers in patients with surgically resected non-small cell lung cancer (NSCLC). PATIENTS, METHODS: STUDY PARTICIPANTS: 290 patients with surgically resected and histopathologically confirmed NSCLC. The maxmum standardized uptake value (SUVmax) and metabolic tumour volume (MTV) of the primary tumour were obtained on 18F-FDG PET/ computed tomography (CT) for initial staging and Ki-67 labeling index (LI), p16, CD31 and cyclin E were evaluated in the primary tumours by immunohistochemical staining. Survival analyses for variables including PET parameters, immunohistochemical biomarker and other clinical factors were performed using the Kaplan-Meier method and Cox proportional hazards regression analysis. RESULTS: In univariate analyses, tumour stage, tumour size, and MTV were significant prognostic factors for decreased overall survival (OS) and disease-free survival (DFS). Multivariate analyses showed MTV and tumour stage were significant predictors of poor OS (MTV, hazard ratio (HR) = 1.135, p = 0.015; stage, HR = 0.644, p = 0.025) and DFS (MTV, HR = 1.128, p = 0.043; stage, HR = 0.541, p = 0.009). CONCLUSION: The MTV of primary tumours is a significant prognostic factor for survival along with tumour stage in patients with surgically resected NSCLC. The MTV can predict OS and DFS better than immunohistochemical biomarkers. PMID- 26875431 TI - A rare case of osteopetrosis mimicking osteosarcoma: 18F-FDG PET/CT findings in an unexpected diagnosis. PMID- 26875433 TI - Milestones in Genetics of Structural Skin Disorders. PMID- 26875434 TI - The Complexity of Elastic Fiber Biogenesis: The Paradigm of Cutis Laxa. PMID- 26875432 TI - Effects of breast cancer on chronic disease medication adherence among older women. AB - PURPOSE: The purpose of this study was to determine the effects of breast cancer on chronic disease medication adherence among older women. METHODS: The Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data and a 5% random sample of Medicare enrollees were used. Stage I-III breast cancer patients diagnosed in 2008 and women without cancer were eligible. Three cohorts of medication users 66+ years were identified using diagnosis codes and prescription fill records: diabetes, hypertension, and lipid disorders. For each cohort, breast cancer patients were frequency matched to comparison women by age and geographic area. Medication adherence was measured by the proportion of days covered and medication persistence. RESULTS: During the post-baseline period, the percentage of breast cancer patients who were non-adherent was 26.2% for diabetes medication, 28.9% for lipid-lowering medication, and 14.2% for hypertension medication. Breast cancer patients experienced an increased odds of diabetes medication non-adherence [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.07 to 1.95] and were more likely to be non-persistent with diabetes medication (hazard ratio = 1.31; 95%CI: 1.04 to 1.66) relative to women without cancer. The study failed to show a difference between breast cancer and comparison women in the odds of non-adherence to hypertensive (OR = 0.87; 95%CI: 0.71 to 1.05) or lipid-lowering medication (OR = 0. 91; 95%CI: 0.73 to 1.13) with a proportion of days covered threshold of 80%. CONCLUSION: Special attention should be given to the coordination of primary care for older breast cancer patients with diabetes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26875435 TI - Heritable Ectopic Mineralization Disorders: The Paradigm of Pseudoxanthoma Elasticum. PMID- 26875436 TI - Molecular Heterogeneity of Blistering Disorders: The Paradigm of Epidermolysis Bullosa. PMID- 26875437 TI - Heritable Filaggrin Disorders: The Paradigm of Atopic Dermatitis. PMID- 26875438 TI - Genetics of Structural Hair Disorders. PMID- 26875439 TI - Next-Generation Diagnostics for Genodermatoses. PMID- 26875440 TI - Molecular Therapeutics for Heritable Skin Diseases. PMID- 26875441 TI - Heritable Collagen Disorders: The Paradigm of the Ehlers-Danlos Syndrome. PMID- 26875442 TI - Bayesian reclassification statistics for assessing improvements in diagnostic accuracy. AB - We propose a Bayesian approach to the estimation of the net reclassification improvement (NRI) and three versions of the integrated discrimination improvement (IDI) under the logistic regression model. Both NRI and IDI were proposed as numerical characterizations of accuracy improvement for diagnostic tests and were shown to retain certain practical advantage over analysis based on ROC curves and offer complementary information to the changes in area under the curve. Our development is a new contribution towards Bayesian solution for the estimation of NRI and IDI, which eases computational burden and increases flexibility. Our simulation results indicate that Bayesian estimation enjoys satisfactory performance comparable with frequentist estimation and achieves point estimation and credible interval construction simultaneously. We adopt the methodology to analyze a real data from the Singapore Malay Eye Study. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26875443 TI - Principles of Virus Uncoating: Cues and the Snooker Ball. AB - Viruses are spherical or complex shaped carriers of proteins, nucleic acids and sometimes lipids and sugars. They are metastable and poised for structural changes. These features allow viruses to communicate with host cells during entry, and to release the viral genome, a process known as uncoating. Studies have shown that hundreds of host factors directly or indirectly support this process. The cell provides molecules that promote stepwise virus uncoating, and direct the virus to the site of replication. It acts akin to a snooker player who delivers accurate and timely shots (cues) to the ball (virus) to score. The viruses, on the other hand, trick (snooker) the host, hijack its homeostasis systems, and dampen innate immune responses directed against danger signals. In this review, we discuss how cellular cues, facilitators, and built-in viral mechanisms promote uncoating. Cues come from receptors, enzymes and chemicals that act directly on the virus particle to alter its structure, trafficking and infectivity. Facilitators are defined as host factors that are involved in processes which indirectly enhance entry or uncoating. Unraveling the mechanisms of virus uncoating will continue to enhance understanding of cell functions, and help counteracting infections with chemicals and vaccines. PMID- 26875444 TI - Vigilant attentiveness in families observing deterioration in the dying intensive care patient: A secondary analysis study. AB - BACKGROUND: Family support in intensive care is often focussed on what information is communicated to families. This is particularly important during treatment withdrawal and end of life care. However, this positions families as passive receivers of information. Less is known about what bereaved family members actually observe at end of life and how this is interpreted. AIM: Secondary analysis study was conducted in order to explore the concept of vigilant attentiveness in family members of adult patients dying in intensive care. METHOD: Secondary analysis of eight interviews sorted from two primary data sets containing 19 interviews with 25 bereaved family members from two intensive care units in England was undertaken. Directed content analysis techniques were adopted. FINDINGS: Families are observant for physiological deterioration by watching for changes in cardiac monitors as well as paying attention to how their relative looks and sounds. Changes in treatment/interventions were also perceived to indicate deterioration. CONCLUSION: Families are vigilant and attentive to deterioration, implying that families are active participants in information gathering. By clarifying what families notice, or do not notice during the dying trajectory in ICU, health care professionals can tailor information, helping to prepare families for the death of their relative. PMID- 26875445 TI - Membrane engineering via trans unsaturated fatty acids production improves Escherichia coli robustness and production of biorenewables. AB - Constructing microbial biocatalysts that produce biorenewables at economically viable yields and titers is often hampered by product toxicity. For production of short chain fatty acids, membrane damage is considered the primary mechanism of toxicity, particularly in regards to membrane integrity. Previous engineering efforts in Escherichia coli to increase membrane integrity, with the goal of increasing fatty acid tolerance and production, have had mixed results. Herein, a novel approach was used to reconstruct the E. coli membrane by enabling production of a novel membrane component. Specifically, trans unsaturated fatty acids (TUFA) were produced and incorporated into the membrane of E. coli MG1655 by expression of cis-trans isomerase (Cti) from Pseudomonas aeruginosa. While the engineered strain was found to have no increase in membrane integrity, a significant decrease in membrane fluidity was observed, meaning that membrane polarization and rigidity were increased by TUFA incorporation. As a result, tolerance to exogenously added octanoic acid and production of octanoic acid were both increased relative to the wild-type strain. This membrane engineering strategy to improve octanoic acid tolerance was found to require fine-tuning of TUFA abundance. Besides improving tolerance and production of carboxylic acids, TUFA production also enabled increased tolerance in E. coli to other bio products, e.g. alcohols, organic acids, aromatic compounds, a variety of adverse industrial conditions, e.g. low pH, high temperature, and also elevated styrene production, another versatile bio-chemical product. TUFA permitted enhanced growth due to alleviation of bio-product toxicity, demonstrating the general effectiveness of this membrane engineering strategy towards improving strain robustness. PMID- 26875446 TI - Fish, long-chain omega-3 polyunsaturated fatty acid intake and incidence of atrial fibrillation: A pooled analysis of two prospective studies. AB - BACKGROUND & AIMS: Whether high intakes of fish and long-chain omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF) remains uncertain. Thus, we aimed to evaluate the associations of total fish, types of fish, and omega-3 PUFA intake with AF incidence in a large prospective study. METHODS: We used data from the Cohort of Swedish Men and the Swedish Mammography Cohort to examine the associations of fish consumption and long-chain omega-3 PUFA intake with AF incidence. At baseline, information on fish and omega 3 PUFA intakes was available from 72,984 men and women, aged 45-83 years, without cardiac disease. Cases of AF were identified through linkage with the Swedish National Patient Register. Multivariable-adjusted relative risks were estimated with the use of Cox proportional hazards models. RESULTS: Over a follow-up period of 12 years, 6095 participants (3595 men and 2500 women) developed AF. Intakes of total fish, fatty fish (herring/mackerel and salmon/whitefish/char), and long chain omega-3 PUFAs were not associated with AF incidence after adjustment for other risk factors. However, high consumption of lean fish (cod/saithe/fish fingers) was associated with a lower risk; multivariable relative risk of AF for >=3 servings/week compared with never consumption was 0.79 (95% confidence interval, 0.65-0.95). CONCLUSIONS: These findings do not support a beneficial association of fatty fish or omega-3 PUFA intake with incident AF. The association between lean fish consumption and AF risk warrants further investigation. PMID- 26875447 TI - Energy-restricted, high-protein diets more effectively impact cardiometabolic profile in overweight and obese women than lower-protein diets. AB - BACKGROUND & AIMS: High-protein energy-restricted diets have demonstrated efficacy in promoting weight loss in overweight and obesity. However, the protein percentage that achieves optimal efficacy and acceptability remains unknown. We sought to assess the effects of three energy-reduced diets with different percentages of calories from protein (20%, 27%, and 35%) on weight loss and lipids. Secondary outcomes included diet acceptability and compliance. METHODS: Six-month, randomized study included women aged 18-80 years with BMI of 27.5-45 kg/m2 and who were not taking lipid-lowering drugs. We randomly assigned 91 women to one of three calorie-reduced diets with: protein, 20%, 27%, or 35% (80% from animal protein); carbohydrates, 50%, 43%, or 35%; fat, 30%. Dietary intervention involved individual visits with a nutritionist every 2 weeks during the first 3 months. We performed a follow-up visit at 6 months. RESULTS: Eighty women aged 44.0 +/- 9.08 years with BMI of 37.7 +/- 3.39 kg/m2 completed the study. At 3 months, weight loss was -8.16 +/- 4.18 kg, -9.66 +/- 5.28 kg, and -10.7 +/- 4.28 kg in the 20%, 27%, and 35%-protein groups, respectively (P = 0.16). These figures slightly and homogeneously increased at 6 months. Around 65% of women following 35%-protein diet lost >=10% of body weight vs. ~33% in 20%-protein group (P = 0.023). Significant decreases occurred in fat mass, lipids and insulin resistance, especially in the 35%-protein group (P < 0.05 vs. 20% protein). This improvement was not fully explained by weight loss. Triglyceride change was negatively correlated with animal-protein intake. All groups provided similar responses to an acceptance, palatability, and satisfaction questionnaire. CONCLUSIONS: An energy-restricted diet with 35% protein, mostly of animal origin, more effectively impacts cardiometabolic profile than an energy-restricted diet with lower protein content although no clear benefit between diets in terms of overall weight loss was observed. The high-protein diet displayed an excellent safety profile and acceptability. This trial was registered in ClinicalTrials.gov as NCT02160496. CLINICAL TRIAL REGISTRATION: The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02160496). PMID- 26875448 TI - Frequency conversion of structured light. AB - Coherent frequency conversion of structured light, i.e. the ability to manipulate the carrier frequency of a wave front without distorting its spatial phase and intensity profile, provides the opportunity for numerous novel applications in photonic technology and fundamental science. In particular, frequency conversion of spatial modes carrying orbital angular momentum can be exploited in sub wavelength resolution nano-optics and coherent imaging at a wavelength different from that used to illuminate an object. Moreover, coherent frequency conversion will be crucial for interfacing information stored in the high-dimensional spatial structure of single and entangled photons with various constituents of quantum networks. In this work, we demonstrate frequency conversion of structured light from the near infrared (803 nm) to the visible (527 nm). The conversion scheme is based on sum-frequency generation in a periodically poled lithium niobate crystal pumped with a 1540-nm Gaussian beam. We observe frequency converted fields that exhibit a high degree of similarity with the input field and verify the coherence of the frequency-conversion process via mode projection measurements with a phase mask and a single-mode fiber. Our results demonstrate the suitability of exploiting the technique for applications in quantum information processing and coherent imaging. PMID- 26875449 TI - Heme: Modulator of Plasma Systems in Hemolytic Diseases. AB - Hemolytic diseases such as sickle-cell disease, beta-thalassemia, malaria, and autoimmune hemolytic anemia continue to present serious clinical hurdles. In these diseases, lysis of erythrocytes causes the release of hemoglobin and heme into plasma. Extracellular heme has strong proinflammatory potential and activates immune cells and endothelium, thus contributing to disease pathogenesis. Recent studies have revealed that heme can interfere with the function of plasma effector systems such as the coagulation and complement cascades, in addition to the activity of immunoglobulins. Any perturbation in such functions may have severe pathological consequences. In this review we analyze heme interactions with coagulation, complement, and immunoglobulins. Deciphering such interactions to better understand the complex pathogenesis of hemolytic diseases is pivotal. PMID- 26875450 TI - Novel Immunotherapeutic Avenues for Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate lymphocyte function, followed by the development of small molecules to target intracellular signaling. Nevertheless, only a minority of patients can achieve disease remission, especially long term, warranting further investigation into newer therapeutic options. Targeting single proinflammatory pathways may not be sufficient, as suggested by variable results with T helper (Th)-17-related cytokine blockade. Multilevel information from 'omics' techniques along with data from mechanistic studies might facilitate the identification of pivotal checkpoints in RA disease pathogenesis and the subsequent development of new effective treatments. PMID- 26875451 TI - Exfoliation and Raman Spectroscopic Fingerprint of Few-Layer NiPS3 Van der Waals Crystals. AB - The range of mechanically cleavable Van der Waals crystals covers materials with diverse physical and chemical properties. However, very few of these materials exhibit magnetism or magnetic order, and thus the provision of cleavable magnetic compounds would supply invaluable building blocks for the design of heterostructures assembled from Van der Waals crystals. Here we report the first successful isolation of monolayer and few-layer samples of the compound nickel phosphorus trisulfide (NiPS3) by mechanical exfoliation. This material belongs to the class of transition metal phosphorus trisulfides (MPS3), several of which exhibit antiferromagnetic order at low temperature, and which have not been reported in the form of ultrathin sheets so far. We establish layer numbers by optical bright field microscopy and atomic force microscopy, and perform a detailed Raman spectroscopic characterization of bilayer and thicker NiPS3 flakes. Raman spectral features are strong functions of excitation wavelength and sample thickness, highlighting the important role of interlayer coupling. Furthermore, our observations provide a spectral fingerprint for distinct layer numbers, allowing us to establish a sensitive and convenient means for layer number determination. PMID- 26875453 TI - [The re-exploration of Mycoplasma pneumoniae infections in children]. PMID- 26875452 TI - Effect of excessive CO2 on physiological functions in coastal diatom. AB - Rising dissolution of anthropogenic CO2 in seawater may directly/indirectly cause ocean acidification and desalination. However, little is known about coastal physiological functions sensitivity to these processes. Here we show some links between ocean acidification/desalination and physiological functions in Thalassiosira weissflogii. Cell density (CD), protein, chlorophyll a (Chl a), malonaldehyde (MDA), superoxide dismutase (SOD), and carbonic anhydrase (CAs) were determined for the assessment of algal biomass, nutritional value, photosynthesis and respiration, lipid peroxidation, antioxidant capacity, and carbon sequestration ability. The influence of pH on the algal Chl a and MDA were extremely significant (P < 0.01). Salinity (S) on cell density and acidity (pH) on protein was significant (0.01 < P < 0.05). Additionally, a significant negative-correlation was observed between cell density and CAs. CAs and SOD had negatively correlations with CD, Chl a, protein, and MDA under pH or S influence, but positive correlation between themselves. Coastal physiological functions were affected by increasing order was acidification < acidification + desalination < desalination for Chl a and protein, desalination < acidification + desalination < acidification for SOD and CAs. Thus, the ongoing excessive CO2-driven ocean acidification and desalination should be of high attention when assessing the risks of climate change on coastal phytoplankton. PMID- 26875454 TI - [Some hot issues on Mycoplasma pneumoniae infections]. PMID- 26875455 TI - [Clinical microbiology of Mycoplasma pneumoniae]. PMID- 26875456 TI - [Epidemiology of Mycoplasma Pneumoniae infections]. PMID- 26875457 TI - [Pathogenic mechanism of Mycoplasma pneumoniae infections]. PMID- 26875458 TI - [The diagnosis of Mycoplasma pneumoniae infections]. PMID- 26875459 TI - [Consensus on off-label use of drugs in pediatric patients in China]. PMID- 26875460 TI - [Value of clinical signs in the identification of Mycoplasma pneumonia in community acquired pneumonia in children]. AB - OBJECTIVE: To evaluate the value of clinical signs in the identification of Mycoplasma pneumonia in children's community acquired pneumonia. METHOD: We searched the Cochrane library, PubMed, CNKI, Wan Fang and VIP databases. According to the inclusion and exclusion criterias, we selected and extracted the related information in the literature. According to the QUADAS evaluation system, we established the quality evaluation standard to evaluate the quality of the included studies and analyzed the difference of the clinical manifestations between Mycoplasmae pneumoniae and non-Mycoplasma pneumoniae in children's community acquired pneumonia. We used the RevMan 5.3 software to do the meta analysis and collected the data according to the requirements. We calculated the pooled sensitivities, specificities and 95%CIs. Then we calculated the negative and positive likelihood ratio, the ratio of the diagnosis and the pre-/post-test probabilities with 95% CIs. RESULT: A total of 11 articles were included in the literature. In summary, the cases of the clinical signs of true positive (TP) and false positive (FP) were as follows : chest pain: TP: 287, FP: 1090; rales: TP: 1906, FP: 6886; headache: TP: 590, FP: 2051; pleural effusion: TP: 10, FP: 16; consolidation: TP: 75, FP: 83; emphysema: TP: 443, FP: 116. The pooled sensitivity, the pooled specificity, the diagnostic ratio (DOR) and 95% CI were: chest pain: pooled sensitivity: 0.12, 95% CI: 0.10-0.13, pooled specificity: 0.89, 95% CI: 0.88-0.90, DOR: 1.05, 95% CI: 0.92-1.21; rales: pooled sensitivity: 0.66, 95% CI: 0.64, 0.67, pooled specificity: 0.36, 95% CI: 0.35, 0.37, DOR: 1.12, 95% CI: 1.02, 1.22; headache: pooled sensitivity: 0.23, 95% CI: 0.21-0.25, pooled specificity: 0.80, 95%CI: 0.79-0.80, DOR: 1.16, 95%CI: 1.05-1.29; pleural effusion: pooled sensitivity: 0.04, 95% CI: 0.02, 0.08, pooled specificity: 0.98, 95% CI: 0.96, 0.99, DOR: 1.28, 95% CI: 0.56, 2.89; consolidation: pooled sensitivity: 0.32, 95% CI: 0.26, 0.39, pooled specificity: 0.87, 95% CI: 0.84, 0.90, DOR: 1.88, 95% CI: 1.23, 2.90; emphysema: pooled sensitivity: 0.22, 95% CI: 0.17, 0.29, pooled specificity: 0.73, 95% CI: 0.69, 0.77, DOR: 1.05, 95% CI: 0.68, 1.61. CONCLUSION: The value of clinical symptoms and signs in the identification of mycoplasma pneumonia in children's community acquired pneumonia was not significant. Although the clinical symptoms/signs of chest pain, headache, rales and chest X-ray manifestations of pleural effusion, consolidation, emphysema could suggest Mycoplasma pneumoniae infection, the presence or absence of any clinical signs were not positive or negative indicators for the identification of Mycoplasma pneumoniae infections. PMID- 26875461 TI - [A systematic review of the therapy for Mycoplasma pneumoniae infections in children]. AB - OBJECTIVE: To evaluate the therapeutic effects of antibacterial agents, glucocorticoid and intravenous immunoglobulin (IVIG) in treating Mycoplasma pneumoniae(MP) infections. METHOD: The literature was screened by the inclusion and exclusion criteria after searching at Cochrane Library, Pubmed, Wanfang, CNKI, and Weipu databases. According to JADAD evaluation system, the relevant information in each included report from the literature was evaluated. The evidence-based analysis was performed for the therapeutic effects of macrolides, glucocorticoid, and IVIG in treating MP infections. Meta-analysis was conducted on the suitable literature by RevMan 5.3 software supplied by Cochrane collaboration. Descriptive analysis was conducted on the literature unsuitable for meta-analysis. RESULT: (1) Seven foreign RCT reports and 7 domestic RCT reports were included in the analysis of the therapeutic effect of macrolides. There was a high heterogeneity among the 7 foreign reports. Five of these reports showed no significant difference in clinical effects between macrolides and non macrolide antibacterial agents. The forest plot analysis of antipyretic timing and cough duration in the domestic literature with complete indicators suggested that for azithromycin sequential therapy vs. erythromycin intravenous therapy, the mean difference of antipyretic timing was-1.10 (95% CI: -1.60,-0.60) and the mean difference of cough duration was-1.56 (95% CI: -2.10,-1.03). (2) Three foreign RCT reports and 5 domestic RCT were included in the analysis of glucocorticoid therapy. The JADAD scores of all the reports were 1. The basic therapy drug was macrolides. The results of sub-group analysis suggested that for the patients who used glucocorticoid early vs. the patients who used non glucocorticoid therapy, the mean difference of antipyretic time was-1.77(95% CI: 2.44,-1.10) and the mean difference of cough duration was-2.47 (95% CI: -2.86, 2.08); for the patients treated with glucocorticoid at 10 days after onset of diseases vs. the patients received non-glucocorticoid therapy, the mean difference of antipyretic time was-3.41 (95% CI: -4.10,-2.73) and the mean difference of cough duration was-2.25 (95%CI: -4.38,-0.12). (3) Regarding IVIG, all the included reports were case study or case report. Most of the literature focused on severe Mycoplasma pneumoniae infection and those with extrapulmonary complications. The limited results suggested a trend of the shortening of disease process and improvement of clinical symptoms by IVIG. CONCLUSION: There was no exact evidence of the therapeutic effects of antibacterial agents in Mycoplasma pneumoniae infections. A trend of better therapeutic effect was inferred in macrolide antibiotics, especially azithromycin. The improvement of clinical symptoms was suggested with the usage of glucocorticoid as adjuvant therapy. IVIG as an adjuvant therapy is at an exploration stage. PMID- 26875462 TI - [Multicenter prospective epidemiological studies on Haemophilus influenzae infection among hospitalized children with lower respiratory tract infections]. AB - OBJECTIVE: To understand epidemiological characteristics of Haemophilus influenzae (Hi) infection in hospitalized children with lower respiratory tract infection (LRTI) in west Sichuan China. METHOD: The multicenter prospective cross sectional design was used; four hospitals in west Sichuan China were chosen as research field, sputum bacterial culture was done and biological typing, PCR identification and drug sensitivity test of Hi epidemic strains were carried out among 0-17y hospitalized patients with LRTI in four hospitals located in west Sichuan China. RESULT: Totally 5 748 cases with LRTI in four hospitals were investigated in west Sichuan from Nov. 2013 to April 2014 and the rate of sputum culture was 46.96% (2,699/5 748). The total pathogenic bacteria positive rate of sputum culture was 43.53% (1,175/2 699), and 279 Haemophilus influenzae (Hi) strain in 272 cases were isolated, the Hi positive rate was 10.08% (272/2 699). All the strains (100%) were non-typeable Haemophilus influenzae (NTHi ) indentified by PCR. The main biotype of 279 strains was type I with 39.07% (109/279) and type IV with 50.90% (142/279) ; 272 cases were enrolled in this survey, 12.50% (34/272) had broncheolitis, the rest of lower respiratory infection was 87.50 % (238/272), and 2.57% (7/272) was neonatal pneumonia, 2.21%(6/272)was pneumonia complicated with sepsis; in four hospitals the overall positive rate of Hi in inpatients with lower respiratory infection was 10.21%, 28.96%, 4.80%, 10.21% (chi(2) = 112.561, P = 0.000) and the positive rate of Hi inpatients with broncheolitis was 11.92%, 20.93%, 4.76%, and 66.67% (Fisher exact probability P = 0.001), with the rest lower respiratory infection was 9.96%, 30.90%, 4.81%, 9.85% (chi(2) =108.876, P = 0.000); 2.87% (8/279) bacterial strains of beta-lactamase-nonproducing-ampicillin-intermediary (BLNAI) distributed in four hospitals, and 1.79% (5/279) bacterial strains of beta lactamase-nonproducing-ampicillin-resistant (BLNAR), 0.72% (2/279) bacterial strains of beta-lactamase-positive amoxicillin-clavulanate-resistance (BLPACR) were found in two hospitals respectively. CONCLUSION: All the Hi isolated from sputum were non-typeable among 0-17y inpatients with LRTI and the main biotype were type I and type IV in west Sichuan China. Much attention should be paid to BLNAR and BLPACR strains found in the west Sichuan region. PMID- 26875463 TI - [Significance of ikaros family zinc finger 1 deletion in pediatric B-acute lymphoblastic leukemia without reproducible cytogenetic abnormalities]. AB - OBJECTIVE: To identify ikaros family zinc finger1 (IKZF1) deletion in patients with pediatric B cells-acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnomalities and further investigate its value in this part of patients' pathogenesis and prognosis. METHOD: The study was approved by the institutional review board of the authors' hospital and informed consent was obtained from the patients and/or their legal guardians. Data of 96 children with B-ALL patients without reproducible cytogenetic abnormalities whose bone marrows specimens were enough for DNA extraction for the detection were retrospectively selected. All the patients were diagnosed and systematically treated according to CCLG-ALL2008 in our hospital from April 2008 to April 2013. The 96 patients were divided into two groups according to the result of IKZF1's detection by multiplex ligation-dependent probe amplification (MLPA): The cases that with any of eight exons of IKZF1 deleted were entered into"Group with IKZF1 deletion"otherwise entered"Group without IKZF1 deletion". Disease free survival (DFS), event-free survival (EFS) and overall survival (OS) were compared between the two groups. RESULT: Nineteen out of 96 B-ALL patients without reproducible cytogenetic abnormalities had IKZF1 deletion (20%). Three of 19 patients with IKZF1 deletions of the whole gene; ten of 19 patients with IKZF1 deletions of exon 1; 4 of 19 patients with IKZF1 deletions of exons 4-7; one of 19 patients with IKZF1 deletions of exons 2-7 and one of 19 patients with IKZF1 deletions of exons 1-6. Whose white blood cell (WBC) >= 50 * 10(9)/L inIKZF1 diletion group was more than whthout IKZF1 deletion group(42% vs. 13%, P=0.004). Patients with IKZF1 deletions had a lower 3-year DFS (0.67 +/- 0.13 vs. 0.93 +/- 0.04, P=0.001); EFS (0.67 +/- 0.13 vs. 0.90 +/- 0.04, P = 0.012) and OS(0.79 +/- 0.09 vs. 0.96 +/- 0.02, P=0.010) compared to those without IKZF1 deletions. Excluding the influence of sex, age, WBC count at diagnosis, cerebrospinal fluid state and prednisone response IKZF1 deletion still affected the patients' DFS, EFS and OS ( P<0.05 for all comparisons). CONCLUSION: Some of pediatric B-cell precursor ALL without reproducible cytogenetic abnormalities had been detected to have IKZF1 deletion; IKZF1 deletion is an independent poor prognostic factor in these patients. PMID- 26875464 TI - [Effects of propranolol on oxygen-induced retinal neovascularization in mouse]. AB - OBJECTIVE: To investigate whether propranolol application as collyrium or intraperitoneal (IP) injection can promote the recovery of oxygen-induced retinopathy (OIR). METHOD: Thirty-six 7-day-old mice were divided into the following 6 groups: normal control, propranolol eye drops, propranolol IP injection, eye drops negative control, IP injection negative control, and pathological model with 6 mice in each. In a typical model of OIR, litters of mice pups with their nursing mothers were exposed to an infant incubator to high oxygen concentration (75 +/- 5)% between postnatal day (PD) 7 and PD12, prior to returning to room air. Two routes of propranolol treatment were assessed from PD12 to PD17: IP injection and eye drop, with doses 2 mg/(kg.time), three times a day. Another three groups were given citric acid buffer eye drops, IP injection of citric acid buffer, and negative control were not treated with any drug. Neonatal mice fed in normal conditions served as normal control. Mice were sacrificed at PD17 to evaluate the morphological changes of retinal vessels by fluorescein isothiocyanate-dextran perfusion and retinal whole mount. The retinal neovascularization was evaluated by counting the number of nuclei of the endothelial cell breaking through the internal limiting membrane (ILM). RESULT: Compared with the oxygen-exposed group, the branches of retinal vessels went normal with a less un-perfused area in the propranolol eye drops and propranolol IP injection groups [(38.9 +/- 9.9)% and (5.6 +/- 2.3)% vs. (16.2 +/- 10.0)% and (2.2 +/- 0.8)%, (25.9 +/- 5.0)% and (2.1 +/- 2.7)%, F=36.12 and 14.55, P both<0.001]. The number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol eye drops group decreased (14.2 +/- 5.1) per slide, which was less than that in the oxygen-exposed group (49.1 +/ 8.9) per slide and the propranolol IP injection group (18.0 +/- 5.9) per slide; it was also less than that in the eye drops negative control group (47.4 +/- 8.1) per slide (F=187.60, P<0.05). Moreover, the number of nuclei of endothelial cells breaking through the ILM on the retinal cross-section in the propranolol IP injection group was less than that in the IP injection negative control group (49.9 +/- 7.1) per slide (P<0.05). CONCLUSION: Propranolol could effectively inhibit the formation of retinal neovascularization in mice; the eye drops was more effective than the IP injection. PMID- 26875465 TI - [Analysis of the etiology of hemoptysis and its diagnosis and treatment in 106 cases]. AB - OBJECTIVE: To investigate the etiology and clinical manifestation of hemoptysis in children. METHOD: A retrospective analysis was performed for 106 cases of hemoptysis who were admitted to The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University from January 2005 to December 2014.The clinical information including laboratory tests and image data were collected and analyzed. RESULT: A total of 106 patients (50 males and 56 females) were identified. The median age was 9.1 years (range 2 months to 18 years). Pneumonia (35, 31.1%) was the most common etiology of hemoptysis, which included bacterial pneumonia (27 cases), mycoplasmal pneumonia(4 cases), chlamydial pneumonia (3 cases), and influenza pneumonia(1 case). Other causes included bronchitis(15, 14.2%), pulmonary tuberculosis (11, 10.4%), bronchiectasis (11, 10.4%), diffuse alveolar hemorrhage (8, 7.5%), idiopathic pulmonary hemosiderosis(6, 5.7%), cardiovascular dysplasia(6, 5.7%), pulmonary contusion (4, 3.8%), foreign body in bronchus (2, 1.9%), allergic bronchopulmonary aspergillosis (2, 1.9%). Eighty-six patients manifested mild hemoptysis; moderate and massive hemoptysis were found in nine and eleven patients, respectively. Pneumonia accounted for 33.7% of mild hemoptysis and 45.5% of massive hemoptysis were due to bronchiectasis; 80.2% were treated with antibiotics and 41.5% were given hemostatic agents; 8.5% received lobectomy. Ninety-six patients (90.6%) were cured and parents gave up treatment in 4 cases (3.8%). Six patients (5.7%) suffered from recurrent hemoptysis. CONCLUSION: Hemoptysis mainly occurred in children who were older than 6 years, the most common cause of hemoptysis was respiratory tract infection. In most cases, the amount of hemoptysis was small and the overall prognosis was good. PMID- 26875466 TI - [Clinical characteristics and prognosis analysis of vitamin B6 responsive infantile spasms]. AB - OBJECTIVE: To analyze clinical characteristics, treatment and prognosis in a cohort of children with vitamin B6 responsive infantile spasms. METHOD: Ten patients were diagnosed as vitamin B6 responsive infantile spasms in Peking University First Hospital between January 2012 and May 2015.The clinical manifestations, diagnosis and treatment process, video-electroencephalogram, magnetic resonance imaging (MRI), epilepsy related genes and prognosis were retrospectively analyzed. RESULT: Of the 10 patients, 5 were male, and 5 were female. Eight of them were normal at birth, and the other 2 patients had intracranial hemorrhage or anoxia.The age of epilepsy onset was from 3.5 to 8.0 months.All patients presented spasms primarily.Interictal electroencephalogram (EEG) showed hypsarrhythmia at seizures onset. MRI showed normal in 8 patients, and subarachnoid hemorrhage or multiple encephalomalacia foci after hemorrhage respectively in the other 2 patients. The results of blood biochemical, cerebrospinal fluid examination and urinary metabolic screening were negative. Epilepsy related genes including ALDH7A1 gene analysis showed wild type in all patients. Two patients were classified as symptomatic and eight might be idiopathic or cryptogenic. The initial dose of vitamin B6 was 10.0 mg/(kg.d). The interval between seizures onset and taking vitamin B6 was 0 to 4.0 months. Seizures disappeared completely within a week after administration of vitamin B6 in 9 patients and in 1.5 months in one patient.Of the 8 patients whose seizures were controlled completely during the follow-up period, 7 patients' EEG recovered within 1.5 to 4.0 months and then continued to be normal. The EEG of the rest of a patient returned to normal, but showed abnormal discharges after stopping taking vitamin B6. Two patients' EEG continued abnormal and seizures recurred due to vitamin B6 withdrawal. At the last follow-up, seizures were controlled in all patients. Drug treatment in one case had stopped. Vitamin B6 was used in 9 patients at a dose of 0.4 to 10.0 mg/(kg.d). Among them, vitamin B6 monotherapy or coadministration with one low dose antiepileptic drug was applied in 6 or 3 patients respectively. The psychomotor development was normal in 5 patients, mild delay in 3 patients, and severe delay in 2 patients with autism behavior. Of the 2 symptomatic patients, one developed normally and the other showed severe delay. CONCLUSION: Vitamin B6 might have effects on both idiopathic or cryptogenic and symptomatic patients, especially for the former. High dose vitamin B6 should be first tried in all patients with infantile spasms. Patients who had response to vitamin B6 could be controlled within a short time and might have better outcomes. Seizures were not easy to relapse in those whose seizures were controlled and EEG recovered completely. Vitamin B6 could be gradually reduced during the course and might be withdrawn in the future. The recurrence of seizures was closely related to EEG abnormality. PMID- 26875467 TI - [Efficacy of percutaneous endoscopic gastrostomy in pediatric patients]. AB - OBJECTIVE: To analyze the efficacy of percutaneous endoscopic gastrostomy (PEG) in pediatric patients. METHOD: From October 2011 to October 2014, children in the gastrointestinal ward of Guangzhou Women and Children's Medical Center received PEG or jejunal tube PEG(JET-PEG). The success rate, operation time were recorded. The changes of their weight, enteral nutrition calories and the incidence of pneumonia before and after the first 6 months of operation were compared. Follow up was conducted until October 2014, the recent and long term complications, the length of indwelling time, the replacement or removal of the tube were recorded, the patients swallowing function or the primary disease's outcomes were observed. RESULT: Of the 13 cases, 10 were male, 3 were female, their average age was 2 years (range 1.8 months-9 years). We performed PEG for 12 of the patients who had congenital craniofacial problems that led to feeding difficulties or recurrent cough and pneumonia (6/12), or neurological disorders (6/12) with inability to swallow, and in one case JET-PEG was performed, this child suffered from chronic intestinal pseudo-obstruction with vomiting and abdominal distension. The gastrostomy was successful in all the patients through one operation, the average operation time of PEG was (25 +/- 3) minutes, JET-PEG was 60 minutes. One local skin infection was noted, no long-term complication occurred. In the first 6 months after operation, all the patients gained weight((5.5-30.5) kg postoperation vs. (3.0-30.0) kg preoperation), and 12 cases' enteral nutrition calories increased (from (209-502) to(272-543) kJ/(kg.d)), the incidence of pneumonia decreased in the children who had recurrent pneumonia before the operation (from (0-1.5) to (0-0.16) per month). Until October 2014, their average length of gastric tube indwelling time was 17.8 months (range 4-36 months). In 4 cases PEG tube was removed when they could eat completely independently, the other 9 needed enteral vein nutrition via PEG tube or jejunal tube, in 3 of them balloon type gastric fistula tube was applied. Two of the 13 cases who had cleft palate received stomatological operations when their weight grew to meet the standard. CONCLUSION: PEG and JET-PEG are safe and effective method for enteric nutrition feeding in pediatrics, the technique causes minimal trauma and has rapid postoperative recovery, few complications, good aesthetic appearances and simple nursing, it can significantly improve their nutritional status and quality of life. PMID- 26875468 TI - [Clinical features and antibiotic resistance of Escherichia coli bloodstream infections in children]. AB - OBJECTIVE: To analyze risk factors, clinical features, outcomes and antibiotic resistance of Escherichia coli(E.coli) causing bloodstream infections in children. METHOD: All inpatients with E. coli positive blood culture in Beijing Children's Hospital from January 2012 to May 2014 were enrolled; 112 cases were included, 66 cases (58.9%) were male, and 46 cases(41.1%) were female. Age range was 2 days to 16 years. Among them, 43 cases (38.4%) were neonates, 19 cases (17.0%) aged from 1 month to 1 year, 14 cases (12.5%) were 1-3 years old, and 36 cases (32.1%) were over three years old. We analyzed the divisions to which the patients were admitted, source of infection, underlying diseases, clinical characteristics, antibiotic resistance, and treatment outcomes, etc. RESULT: Forty-six cases (41.1%) were treated in division of hematology, 42 (37.5%) in neonatology, 9 (8.0%) in internal medicine, 8 (7.1%) in surgery, and 7 (6.3%) in pediatric intensive care unit. Sixty-five cases(58.0%) had underlying diseases. Fever was the most frequently presented symptom, as it was seen in 91 cases (81.3%); 52 cases(46.4%) had respiratory symptoms. Among these, 43 cases had pneumonia, 3 cases had respiratory failure, 3 cases were diagnosed as upper respiratory tract infection, 2 had pulmonary hemorrhage and 1 case had bronchitis. Twenty-six cases (23.2%)were diagnosed as severe sepsis and purulent meningitis separately, 14 cases(12.5%) had urinary tract infection. There were 73 (65.2%) strains inducing extended spectrum beta-lactamases (ESBLs), of which 6 (8.2%) and 10 (13.7%) strains were resistant to amikacin and carbapenems respectively. Resistance rate against other antimicrobial agents varied from 64.6% to 100%. OUTCOMES: 92 (82.1%) cases were cured or had improvement while 20 patients (17.9%) died or could not be cured at the end of treatment. Positive ESBLs (chi(2) = 6.609, P = 0.010), being complicated with severe sepsis (chi(2) = 40.253, P = 0.000) and requiring mechanical ventilation (chi(2) = 34.441, P = 0.000) indicate poor prognosis. CONCLUSION: Patients with underlying diseases and newborns are susceptible to E. coli bloodstream infection. ESBLs infection, severe sepsis and mechanical ventilation indicate poor prognosis in E. coli blood stream infection. Clinicians may use carbapenems as empirical treatment for ESBLs infection. There may be carbapenem-resistant enterobacteriaceae strains infection if patients receiving treatment with carbapenems have no response. PMID- 26875469 TI - [A case of hypersarcosinaemia]. PMID- 26875470 TI - [A case of Kawasaki disease complicated with capillary leak syndrome, intrahepatic cholestasis]. PMID- 26875471 TI - [Advances in the pathogenesis of vascular endothelial cells injury in Kawasaki disease]. PMID- 26875473 TI - Perceptions of Black College Women on Barriers to HIV-Risk Reduction and Their HIV Prevention Intervention Needs. AB - HIV prevention interventions can help college students engage in safe sexual behaviors. We used the Information, Motivation, Behavioral Skills model to frame four focus group discussions with Black women (n = 32) attending a historically Black college/university or a traditional university to understand their HIV prevention needs. Participants wanted clear information about sexually transmitted infections/HIV and access to contraception. Motivators for practicing safe sex were related to cultural and religious expectations, desire to avoid pregnancy, and conscious efforts to defy racial stereotypes. Barriers to practicing safe sex included issues of accountability, stigma associated with accessing HIV testing/prevention services, and media influences. We found general consensus about the need to develop skill-building HIV prevention interventions focused on communication skills, condom negotiation, access to services, and empowerment. We offer insight into culture- and age-appropriate HIV prevention for Black college women to guide the development of future interventions. PMID- 26875474 TI - Is one measurement enough to evaluate blood pressure among adolescents? A blood pressure screening experience in more than 9000 children with a subset comparison of auscultatory to mercury measurements. AB - Evaluation of blood pressure is recommended in all children older than 3 years. Auscultatory devices are the recommended method to assess blood pressure in pediatrics, but automated oscillometric devices are increasingly common. A retrospective analysis of our school-based blood pressure screening was performed to determine if multiple oscillometric blood pressure measurements are needed to approach true blood pressure. All children had 4 oscillometric measurements of blood pressures and a random subset of 287 had an additional auscultatory measurement. Among 9870 participants, we observed a nonlinear decrease in blood pressure over time. The largest decrease in systolic blood pressure was between first and second (-3.8 mm Hg) and in diastolic from second to third (-3.3 mm Hg) measurement. For systolic blood pressure, the second oscillometric measurement, the average of second to third and the average of first to third were statistically similar to a single auscultatory measurement. We conclude that assessment of blood pressure using oscillometric devices should include at least 3 measurements in the same sitting to avoid inaccurate assessment. PMID- 26875475 TI - Functionalized magnetic dextran-spermine nanocarriers for targeted delivery of doxorubicin to breast cancer cells. AB - In recent decades, targeted drug delivery systems for breast cancer treatment emerged as an ideal alternative and promising solution to reduce systemic side effects of chemotherapeutic agents. In this study, the preparation and characterization of cationic doxorubicin (DOX) loaded magnetic dextran-spermine (DEX-SP) nanocarriers (DEX-SP-DOX) by ionic gelation were fully investigated. Then, anti-HER2 as a monoclonal antibody (mAb) and targeting ligand was conjugated via EDC/NHS reagents. The binding was confirmed by Bradford assay and further assessments were carried out by size and zeta potential measurements. Cytotoxicity effect and internalization of magnetic nanocarriers were assessed by MTT and Prussian blue assays and transmission electron microscopy (TEM), respectively. DLS measurements indicated that the size of nanocarriers increased from 62 to 84 nm by conjugation of anti-HER2 to them. The in vitro release of DOX from mAb conjugated magnetic nanocarriers at pHs 5 and 7.4 was found to be 85 and 55.5%, respectively. The MTT and Prussian blue assays demonstrated enhanced and selective uptake of DEX-SP-DOX-mAb by SKBR cell (HER2 overexpressed cells) in comparison with unconjugated nanocarriers due to higher cellular binding. The TEM result also confirmed cellular internalization of DEX-SP-DOX-mAb magnetic nanocarriers. These results are very promising for targeted delivery of DOX to HER2 positive breast cancer cells. PMID- 26875476 TI - Update on the management of non-obstetric acute abdomen in pregnant patients. AB - Acute abdomen is a rare entity in the pregnant patient, with an incidence of one in 500-635 patients. Its appearance requires a quick response and an early diagnosis to treat the underlying disease and prevent maternal and fetal morbidity. Imaging tests are essential, due to clinical and laboratory masking in this subgroup. Appendicitis and complicated biliary pathology are the most frequent causes of non-obstetric acute abdomen in the pregnant patient. The decision to operate, the timing, and the surgical approach are essential for a correct management of this pathology. The aim of this paper is to perform a review and update on the diagnosis and treatment of non-obstetric acute abdomen in pregnancy. PMID- 26875477 TI - Treatment of presacral bleeding after colorectal surgery with Bakri balloon. PMID- 26875478 TI - [Hospital variation in anastomotic leakage after rectal cancer surgery in the Spanish Association of Surgeons project: The contribution of hospital volume]. AB - OBJECTIVE: This multicentre observational study aimed to determine the anastomotic leak rate in the hospitals included in the Rectal Cancer Project of the Spanish Society of Surgeons and examine whether hospital volume may contribute to any variation between hospitals. METHODS: Hospital variation was quantified using a multilevel approach on prospective data derived from the multicentre database of all adenocarcinomas of the rectum operated by an anterior resection at 84 surgical departments from 2006 to 2013. The following variables were included in the analysis; demographics, American Society of Anaesthesiologists classification, use of defunctioning stoma, tumour location and stage, administration of neoadjuvant treatment, and annual volume of elective surgical procedures. RESULTS: A total of 7231 consecutive patients were included. The rate of anastomotic leak was 10.0%. Stratified by annual surgical volume hospitals varied from 9.9 to 11.3%. In multilevel regression analysis, the risk of anastomotic leak increased in male patients, in patients with tumours located below 12 cm from the anal verge, and advanced tumour stages. However, a defunctioning stoma seemed to prevent this complication. Hospital surgical volume was not associated with anastomotic leak (OR: 0.852, [0.487-1.518]; P=.577). Furthermore, there was a statistically significant variation in anastomotic leak between all departments (MOR: 1.475; [1.321-1.681]; P<0.001). CONCLUSION: Anastomotic leak varies significantly among hospitals included in the project and this difference cannot be attributed to the annual surgical volume. PMID- 26875479 TI - Giant anal tumor. PMID- 26875480 TI - Evaluating the attractiveness of the availability of injectable progestogen contraceptives at the community pharmacy setting in the United Kingdom. AB - INTRODUCTION: Pharmacists have extended opening hours and are located in communities. Many offer sexual and reproductive health services such as emergency contraception. The opportunity to receive injectable contraception from community pharmacists would improve availability of this method and might increase uptake and continuation. A self-administered survey of women attending a large urban sexual and reproductive health clinic was undertaken to determine the acceptability of receiving contraceptive injections from a community pharmacist. METHODS: Women aged 16-50 years attending an NHS walk-in sexual and reproductive health clinic were invited to complete questionnaires while they were waiting to attend an appointment with a clinician. Questionnaires asked women if they were current, previous or never users of the progestogen only injectable, their method of contraception and whether availability of the injectable from a local pharmacist would influence their decision to use this method. RESULTS: Two hundred and forty questionnaires were distributed and 220 completed (92%). A total of 9% of respondents were past users of the injectable (n = 21), 4% were current users (n = 8) and the remaining 87% were never users. Of those 191 current non-users, 33% (n = 64) indicated that they would consider using this method if it was available at the pharmacy. The main perceived advantages of attending the pharmacy were quicker appointments (52%) and easier access (47%). CONCLUSION: Provision of the injectable contraceptive from a pharmacist might make this method attractive to almost one in three women who are not currently using it. This could be a strategy to improve uptake and continuation of this method. PMID- 26875481 TI - The development of an in-house dispensary in a college health center. AB - BACKGROUND AND PURPOSE: A small college health center discovered that students perceived obtaining prescribed medication was a barrier to adherence to short term antibiotic therapy. To address this specific barrier, an in-house dispensary was developed and modified over the past several years to meet the needs of students. Partnering with a local pharmacy has made the process of obtaining prescriptions easier for the students. DATA SOURCES: Data were extracted from the electronic health records at Student Health Services for the academic year 2014 2015. A total of 910 prescriptions were filled in-house during that time, compared to 102 prescriptions written for purchase elsewhere. CONCLUSIONS: Students are utilizing the in-house dispensary more often than taking a prescription to a pharmacy and generally regard the service as convenient. Despite challenges in changing drug prices and other factors that influence medication adherence, dispensing a small number of drugs in the clinic has been feasible and well received. IMPLICATIONS FOR NURSE PRACTITIONERS: Nurse practitioners must be aware of specific perceived barriers for their practice population and develop interventions to overcome them. The evaluation of such interventions is imperative for modifications and sustainability. PMID- 26875483 TI - Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma. AB - Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb. PMID- 26875482 TI - Concentration of Potassium in Plasma, Erythrocytes, and Muscle Tissue in Cows with Decreased Feed Intake and Gastrointestinal Ileus. AB - BACKGROUND: Healthy cows consume large amounts of potassium and a sudden loss in appetite can lead to hypokalemia. The routine method to evaluate potassium homeostasis is the measurement of the extracellular potassium in plasma or serum, but this does not provide information about the intracellular potassium pool. HYPOTHESIS/OBJECTIVES: To evaluate potassium homeostasis by comparing the extracellular and intracellular potassium concentration in cows with reduced feed intake and gastrointestinal ileus. ANIMALS: Twenty cows 1-3 days postpartum (group 1) and 20 cows with gastrointestinal ileus (group 2). METHODS: Observational cross-sectional study. Plasma potassium was measured by using an ion-sensitive electrode. Intracellular potassium was measured in erythrocytes and muscle tissue (muscle biopsy) by using inductively coupled plasma optical emission spectroscopy. RESULTS: Cows of group 1 did not have hypokalemia. Overall cows with gastrointestinal ileus were hypokalemic (mean +/- SD, 2.9 mmol/L +/- 0.78), but potassium concentration in erythrocytes and muscle tissue was not lower than in postpartum cows. Intracellular potassium in erythrocytes varied very widely; group 1: 3497-10735 mg/kg (5559 +/- 2002 mg/kg), group 2: 4139-21678 mg/kg (7473 +/- 4034 mg/kg). Potassium in muscle tissue did not differ between group 1 (3356 +/- 735 mg/kg wet weight) and group 2 (3407 +/- 1069 mg/kg wet weight). No association between extracellular and intracellular potassium concentrations was detected. CONCLUSIONS AND CLINICAL IMPORTANCE: That measurement of plasma potassium concentration is not sufficient to evaluate potassium metabolism of cows. PMID- 26875484 TI - Down Regulation of Asparagine Synthetase and 3-Phosphoglycerate Dehydrogenase, and the Up-Regulation of Serine Dehydratase in Rat Liver from Intake of Excess Amount of Leucine Are Not Related to Leucine-Caused Amino Acid Imbalance. AB - Asparagine synthetase (ASNS), 3-phosphoglycerate dehydrogenase (PHGDH) and serine dehydratase (SDS) in rat liver are expressed in response to protein and amino acid intake. In the present study, we examined the expression of these enzymes in relation to amino acid imbalance caused by leucine. Rats were subjected to leucine administration in the diet or orally between meals. Consumption of more than 2% leucine in a 6% casein diet suppressed food intake and caused growth retardation in a dose-dependent manner, but this was not seen in a 12% or 40% casein diet. ASNS and PHGDH expression in the liver was significantly induced by the 6% casein diet and was suppressed by leucine in a dose-dependent manner, whereas the SDS expression was induced. These effects were leucine specific and not seen with ingestion of isoleucine or valine. However, leucine orally administered between meals did not change the food intake or growth of rats fed a 6% casein die, though it similarly affected the expression of ASNS, PHGDH and SDS in the liver. These results suggest that the growth retardation caused by leucine imbalance was mainly because of the suppression of food intake, and demonstrated that there are no causal relationships between ASNS, PHGDH and SDS expression and amino acid imbalance caused by leucine. PMID- 26875485 TI - Lignosulfonic Acid-Induced Inhibition of Intestinal Glucose Absorption. AB - Lignosulfonic acid is a waste lignin produced from the sulfite pulping of softwood. We investigated the effect of lignosulfonic acid on alpha-glucosidase and found that lignosulfonic acid produced a reversible and non-competitive inhibition of the enzyme activity. Moreover, in human colorectal adenocarcinoma cells, lignosulfonic acid inhibited 2-deoxyglucose uptake, while in vivo studies demonstrated a significant reduction in the blood glycemic response to sucrose or glucose ingestion in rats treated with lignosulfonic acid. Feces of rats fed a diet supplemented with 5% lignosulfonic acid had higher sugar content compared to those of rats fed a control diet. These results suggest that lignosulfonic acid suppresses the rise in blood glucose levels through inhibition of alpha glucosidase activity and intestinal glucose absorption. PMID- 26875486 TI - Gene-Nutrient Interaction between Folate and Dihydrofolate Reductase in Risk for Adenomatous Polyp Occurrence: A Preliminary Report. AB - Folate and related gene variants are significant risk factors in the aetiology of colorectal cancer. Dihydrofolate reductase (DHFR) is critical in the metabolism of synthetic folic acid (pteroylmonoglutamatamic, PteGlu) to tetrahydrofolate following absorption. Therefore, the 19bp deletion variant of DHFR may lead to the alteration of folate-related colorectal disease susceptibility. This study examined the association between PteGlu and 19bp del-DHFR, and adenomatous polyp (AP) occurrence, an antecedent of colorectal cancer. A total of 199 subjects (162 controls and 37 AP cases) were analysed to determine dietary intake of total folate, natural methylfolate and synthetic PteGlu, level of erythrocyte folate and plasma homocysteine (tHcy), and genotype of 19bp del-DHFR. Dietary folate intake, erythrocyte folate, tHcy and 19bp del-DHFR variants did not independently predict the occurrence of AP. However, a gene-nutrient interaction was observed when subjects were stratified according to dietary folate intake. In subjects with a folate intake above the median value due to significant dietary PteGlu content, the presence of the 19bp-deletion allele decreased the risk for AP (OR=0.35, 95% CI: 0.13-0.97). However, such association was not evident in individuals with a folate intake below the median value. In conclusion, the finding suggests that folate nutrition and 19bp del-DHFR variation may interact to modify AP risk. PMID- 26875487 TI - Low Serum Phosphorus Level in Massry's Phosphate Depletion Syndrome May Be One of the Causes of Acute Heart Failure. AB - Hypophosphatemia has been found to be associated with multiple organ dysfunction. In this study we aimed to investigate the association between low serum phosphorus and acute heart failure. A total of 213 subjects, 101 patients with acute heart failure and 112 healthy subjects were included in this case-control study. Serum phosphorus levels, calcium levels, and PTH concentrations were measured. Ejection fraction percentages, pulse rates, systolic and diastolic blood pressures were recorded. The groups were similar in terms of age and gender (p=0.067 and 0.995, respectively). The phosphorus levels and ejection fraction percentages of the patients with heart failure were lower than for the healthy subjects (p<0.001). Frequency of hypophosphatemia was higher in the heart failure group (p<0.001). There was a strong relationship between low serum phosphorus level and acute heart failure (OR 9.85, CI 95% 3.6-26.3, p<0.001). The phosphorus level of patients with acute heart failure was found to be low in this study. Therefore, the phosphorus level should be controlled in patients with acute heart failure and phosphorus supplementation can be a complimentary treatment for these patients. PMID- 26875488 TI - An Efficient Purification Method for Quantitative Determinations of Protodioscin, Dioscin and Diosgenin in Plasma of Fenugreek-Fed Mice. AB - An efficient purification method for simultaneous recovery of polar saponins, protodioscin (PD) and dioscin (DC), and non-polar aglycon, diosgenin (DG), from plasma of mice fed diets containing seed flours of fenugreek (Trigonella foenum graecum) was established for subsequent quantitative analysis by LC-ESI-MS/MS. Mice plasma samples were first deproteinated by addition of acetonitrile, and the supernatant was applied to a carbon-based solid phase extraction tube. After successive washing with methanol and 35% chroloform/methanol (v/v), PD, DC and DG were eluted simultaneously with 80% chroloform/methanol (v/v). The eluate was evaporated to dryness, and re-dissolved in 80% methanol (v/v). The filtered sample was analyzed with an LC-ESI-MS/MS system. After the purification procedure, recovery rates between 89.3 to 117.4% were obtained without notable ion suppression or enhancement. The use of internal standards was therefore not necessary. The utility of the method was demonstrated by analyzing plasma of mice from a fenugreek feeding study. PMID- 26875489 TI - Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin gamma Carboxylation: A Double-Blind, Randomized Controlled Trials. AB - Vitamin K is essential for bone health, but the effects of low-dose vitamin K intake in Japanese subjects remain unclear. We investigated the effective minimum daily menaquinone-7 dose for improving osteocalcin gamma-carboxylation. Study 1 was a double-blind, randomized controlled dose-finding trial; 60 postmenopausal women aged 50-69 y were allocated to one of four dosage group and consumed 0, 50, 100, or 200 MUg menaquinone-7 daily for 4 wk, respectively, with a controlled diet in accordance with recommended daily intakes for 2010 in Japan. Study 2 was a double-blind, randomized placebo-controlled trial based on the results of Study 1; 120 subjects aged 20-69 y were allocated to the placebo or MK-7 group and consumed 0 or 100 MUg menaquinone-7 daily for 12 wk, respectively. In both studies, circulating carboxylated osteocalcin and undercarboxylated osteocalcin were measured. The carboxylated osteocalcin/undercarboxylated osteocalcin ratio decreased significantly from baseline in the 0 MUg menaquinone-7 group, in which subjects consumed the recommended daily intake of vitamin K with vitamin K1 and menaquinone-4 (Study 1). Menaquinone-7 increased the carboxylated osteocalcin/undercarboxylated osteocalcin ratio dose dependently, and significant effects were observed in both the 100 and 200 MUg groups compared with the 0 MUg group. Undercarboxylated osteocalcin concentrations decreased significantly, and the carboxylated osteocalcin/undercarboxylated osteocalcin ratio increased significantly in the 100 MUg menaquinone-7 group compared with the placebo group (Study 2). Daily menaquinone-7 intake >=100 MUg was suggested to improve osteocalcin gamma-carboxylation. PMID- 26875490 TI - beta-Carotene Increases Muscle Mass and Hypertrophy in the Soleus Muscle in Mice. AB - Supplements and naturally occurring nutraceuticals effective for maintenance or enhancement of skeletal muscle mass are expected to contribute to prevention of decreased mobility and increased risk of developing metabolic diseases. However, information about available food components remains widely unavailable. In the present study, we investigated the effects of dietary beta-carotene on the quantity and quality of skeletal muscle under physiological conditions. Male ddY mice (8 wk old) were orally administered beta-carotene (0.5 mg once daily) for 14 d. Dietary beta-carotene had no influence on body weight, but increased the soleus muscle/body weight ratio. The cross-sectional area (CSA) in muscle fibers of the soleus muscle was increased, indicating that administration of beta carotene induces muscle hypertrophy. In the soleus muscle of the beta-carotene administered mice, twitch force tended to be increased (p=0.06) and tetanic force was significantly increased, whereas specific force (force per CSA) remained unchanged. Dietary beta-carotene increased the mRNA level of insulin-like growth factor 1 (Igf-1) as its splicing variant Igf-1ea, but had no influence on the liver Igf-1 mRNA level or serum IGF-1 level. beta-Carotene promoted protein synthesis in the soleus muscle and reduced levels of ubiquitin conjugates, but had no influence on the mRNA levels of two atrogenes, Atrogin-1 and Murf1. On the other hand, beta-carotene had no influence on the processing of the autophagy marker protein light chain 3. These results indicate that in mice, administration of beta-carotene increases mass and induces functional hypertrophy in the soleus muscle, perhaps by promoting IGF-1-mediated protein synthesis and by reducing ubiquitin-mediated protein degradation. PMID- 26875491 TI - Sasa borealis Extract Efficiently Enhanced Swimming Capacity by Improving Energy Metabolism and the Antioxidant Defense System in Mice. AB - This study was conducted to determine the effects of 50% ethanolic extract from Sasa borealis leaves (SBE) on swimming capacity and oxidative metabolism in mice. The mice were divided into 2 groups with similar swimming times and body weights; Ex-Control and Ex-SBE were orally administered with distilled water and 250 mg/kg body weight/d of SBE. Exhaustive swimming times were prolonged by 1.5-fold in the Ex-SBE group compared to the Ex-Control. The Ex-SBE group displayed lower lactate and higher non-esterified fatty acid levels 15 min after swimming and the hepatic and muscle glycogen levels were significantly higher than that in the Ex-Control. SBE potentially enhanced mRNA expression of citrate synthase (CS), carnitine palmitoyltransferase (CPT-1), and beta-hydroxyacyl coenzyme A dehydrogenase (beta HAD) in skeletal muscle. The activities and mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were elevated in the Ex-SBE compared with the Ex-Control after exhaustive swimming. These results suggest that SBE might be used as an effective agent to enhance swimming capacity by utilization of energy substrates and might ameliorate physical exhaustion by facilitating energy-generating metabolic genes and enhancing endogenous antioxidants. PMID- 26875492 TI - Annatto Tocotrienol Induces a Cytotoxic Effect on Human Prostate Cancer PC3 Cells via the Simultaneous Inhibition of Src and Stat3. AB - Prostate cancer is one of the most frequently occurring cancers and often acquires the potential of androgen-independent growth as a malignant phenotype. Androgen-independent prostate cancer has severe chemoresistance towards conventional chemotherapeutic agents, so a new treatment approach is required for curing such prostate cancer. In this context, the present study was undertaken to check if annatto tocotrienol (main component delta-tocotrienol) could suppress cell growth in human prostate cancer (PC3, androgen-independent type) cells via the inhibition of Src and Stat3. The tocotrienol showed cytotoxic effects on PC3 cells in a dose-dependent manner, and the effect depended on G1 arrest in the cell cycle and subsequent induction of apoptosis. In a cytotoxic dose, the tocotrienol suppressed cellular growth via the simultaneous inhibition of Src and Stat3. Similarly, the treatment combination of both Src and Stat3 inhibitors induced cytotoxic effects in PC3 cells in an additive manner compared to each by itself. With respect to cell cycle regulation and the induction of apoptosis, the combination treatment showed a similar effect to that of the tocotrienol treatment. These results suggest that annatto tocotrienol effectively induces cytotoxicity in androgen-independent prostate cancer cells via the suppression of Src and Stat3. PMID- 26875493 TI - Effects of Salmon Nasal Cartilage Proteoglycan on Plasma Glucose Concentration and Active Glucose Transport in the Small Intestine. AB - Recently, proteoglycan was purified from the nasal cartilage of salmon. Although several physiological effects have been reported, the effect of salmon nasal cartilage proteoglycan (salmon PG) on glucose metabolism remains unclear. We studied the effect of salmon PG on rat plasma glucose levels. Oral administration of 1% salmon PG significantly attenuated the increase in portal plasma glucose levels following an oral glucose tolerance test (OGTT). Additionally 1% salmon PG delayed the increase in peripheral glucose concentration induced by the OGTT. Mucosal administration of 1% salmon PG significantly decreased active glucose transport using the everted jejunal sac method. Furthermore, transmural potential difference (DeltaPD) measurements using the everted jejunum revealed that 1% salmon PG significantly decreased glucose-dependent and phlorhizin (inhibitor of sodium-glucose co-transporter 1; SGLT1)-sensitive DeltaPD. These results suggest that salmon PG decreases glucose absorption via SGLT1 in the jejunum, thereby attenuating the increase in portal and peripheral plasma glucose levels in rats. PMID- 26875494 TI - Purification and Properties of Glycine Oxidase from Pseudomonas putida KT2440. AB - Glycine oxidase, encoded by the thiO gene, participates in the biosynthesis of thiamin by providing glyoxyl imine to form the thiazole moiety of thiamin. We have purified and characterized ThiO from Pseudomonas putida KT2440. It has a monomeric structure that is distinct from the homotetrameric ThiOs from Bacillus subtilis and Geobacillus kaustophilus. The P. putida ThiO is unique in that glycine is its preferred substrate, which differs markedly from the B. subtilis and G. kaustophilus enzymes that use D-proline as the preferred substrate. PMID- 26875495 TI - Propionate Promotes Fatty Acid Oxidation through the Up-Regulation of Peroxisome Proliferator-Activated Receptor alpha in Intestinal Epithelial Cells. AB - Short chain fatty acids (SCFAs) are produced in the colonic lumen mainly by bacterial fermentation of dietary fiber. Emerging evidence shows that SCFA has important physiological and pathophysiological effects on colonic and systemic events. Recently, propionate, known as a kind of SCFA, has been shown to lower fatty acid contents in plasma and reduce food intake. However, the detailed mechanism underlying the propionate-mediated lipid metabolism action remains poorly understood. The intestinal lipid metabolism process is critical for systemic energy homeostasis. Therefore, we investigate here the effects of propionate on intestinal lipid metabolism. Results show that propionate induced peroxisome proliferator-activated receptor alpha (PPARalpha) expression time dependently and concentration-dependently in YAMC (a mouse intestinal epithelial cell line) cells. The expression levels of PPARalpha-responsive genes such as carnitine palmitoyl transferase II (CPTII) and trifunctional protein alpha (TFPalpha) were up-regulated in the presence of propionate, thereby suppressing triglyceride (TG) accumulation. Furthermore, propionate-mediated PPARalpha induction required phosphorylation of extracellular signal-regulated kinase. Collectively, these data indicate that propionate regulates intestinal lipid metabolism through the induction of PPARalpha expression. Results suggest that the inhibitory effect of propionate on TG accumulation partly contributes to the propionate-mediated fatty acid-lowering effect. PMID- 26875496 TI - Hedgehog receptor function during craniofacial development. AB - The Hedgehog signalling pathway plays a fundamental role in orchestrating normal craniofacial development in vertebrates. In particular, Sonic hedgehog (Shh) is produced in three key domains during the early formation of the head; neuroectoderm of the ventral forebrain, facial ectoderm and the pharyngeal endoderm; with signal transduction evident in both ectodermal and mesenchymal tissue compartments. Shh signalling from the prechordal plate and ventral midline of the diencephalon is required for appropriate division of the eyefield and forebrain, with mutation in a number of pathway components associated with Holoprosencephaly, a clinically heterogeneous developmental defect characterized by a failure of the early forebrain vesicle to divide into distinct halves. In addition, signalling from the pharyngeal endoderm and facial ectoderm plays an essential role during development of the face, influencing cranial neural crest cells that migrate into the early facial processes. In recent years, the complexity of Shh signalling has been highlighted by the identification of multiple novel proteins that are involved in regulating both the release and reception of this protein. Here, we review the contributions of Shh signalling during early craniofacial development, focusing on Hedgehog receptor function and describing the consequences of disruption for inherited anomalies of this region in both mouse models and human populations. PMID- 26875497 TI - Developmental transcriptomics in Atlantic haddock: Illuminating pattern formation and organogenesis in non-model vertebrates. AB - Gadiforms such as Atlantic haddock comprise some of the world's most economically important fisheries. Understanding the early life history of these fish is a prerequisite for predicting effects of a changing environment and increased human activities. Robust assessment of the effects of environmental impacts on the embryos of non-model vertebrates is hampered by a lack of molecular resources and detailed knowledge regarding the regulation of genes and pathways in early development. Here we used mRNA sequencing to link transcriptional changes to developmental processes in haddock, specifically, pattern formation and organogenesis. Temporal expression of key developmental genes was tightly anchored to either the appearance of visible structures or cellular processes characterised in model organisms. These findings demonstrate the high potential of developmental transcriptomics as an analytical tool for improved understanding of pathophysiological mechanisms leading to abnormal development in any vertebrate. PMID- 26875498 TI - Thermal degradation mechanism of triangular Ag@SiO2 nanoparticles. AB - Triangular silver nanoparticles are promising materials for light harvesting applications because of their strong plasmon bands; these absorption bands are highly tunable, and can be varied over the entire visible range based on the particle size. A general concern with these materials is that they are unstable at elevated temperatures. When thermally annealed, they suffer from changes to the particle morphology, which in turn affects their optical properties. Because of this stability issue, these materials cannot be used in applications requiring elevated temperatures. In order to address this problem, it is important to first understand the degradation mechanism. Here, we measure the changes in particle morphology, oxidation state, and coordination environment of Ag@SiO2 nanotriangles caused by thermal annealing. UV-vis spectroscopy and TEM reveal that upon annealing the Ag@SiO2 nanotriangles in air, the triangular cores are truncated and smaller nanoparticles are formed. Ag K-edge X-ray absorption spectroscopy (XANES and EXAFS) shows that the small particles consist of Ag(0), and that there is a decrease in the Ag-Ag coordination number with an increase in the annealing temperature. We hypothesize that upon annealing Ag in air, it is first oxidized to AgxO, after which it subsequently decomposes back to well dispersed Ag(0) nanoparticles. In contrast, when the Ag@SiO2 nanotriangles are annealed in N2, since there is no possibility of oxidation, no small particles are formed. Instead, the triangular core rearranges to form a disc-like shape. PMID- 26875500 TI - Effect of Shufeng Jiedu capsules as a broad-spectrum antibacterial. AB - This study sought to investigate the broad-spectrum antibacterial action of an alternative medicine, Shufeng Jiedu capsules (SFJDC). Antibacterial testing was performed to determine whether SFJDC had broad-spectrum antibacterial action in vitro, and testing was performed to verify whether SFJDC prevented death due to a Streptococcus or Staphylococcus aureus infection in mice. Results of antibacterial testing suggested that SFJDC are a broad-spectrum antibacterial and that SFJDC are superior to Lianhua Qingwen capsules as a broad-spectrum antibacterial. Results of testing revealed that SFJDC lowered the mortality rate, it reduced mortality, it increased average survival time, and it increased the lifespan of mice dying due to a Staphylococcus aureus or Streptococcus infection. Thus, SFJDC could become a complement to broad-spectrum antimicrobials in clinical settings. PMID- 26875499 TI - Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering. AB - Disorazol, a macrocyclic polykitide produced by the myxobacterium Sorangium cellulosum So ce12 and it is reported to have potential cytotoxic activity towards several cancer cell lines, including multi-drug resistant cells. The disorazol biosynthetic gene cluster (dis) from Sorangium cellulosum (So ce12) was identified by transposon mutagenesis and cloned in a bacterial artificial chromosome (BAC) library. The 58-kb dis core gene cluster was reconstituted from BACs via Red/ET recombineering and expressed in Myxococcus xanthus DK1622. For the first time ever, a myxobacterial trans-AT polyketide synthase has been expressed heterologously in this study. Expression in M. xanthus allowed us to optimize the yield of several biosynthetic products using promoter engineering. The insertion of an artificial synthetic promoter upstream of the disD gene encoding a discrete acyl transferase (AT), together with an oxidoreductase (Or), resulted in 7-fold increase in disorazol production. The successful reconstitution and expression of the genetic sequences encoding for these promising cytotoxic compounds will allow combinatorial biosynthesis to generate novel disorazol derivatives for further bioactivity evaluation. PMID- 26875501 TI - A differential impact of lithium on endothelium-dependent but not on endothelium independent vessel relaxation. AB - Lithium is drug for bipolar disorders with a narrow therapeutic window. Lithium was recently reported to prevent stroke and protect vascular endothelium but tends to accumulate particularly in the brain and kidney. Here, adverse effects are common; however mechanisms are still vaguely understood. If lithium could also negatively influence the endothelium is unclear. We hypothesize that at higher lithium levels, the effects on endothelium reverses--that lithium also impairs endothelial-dependent relaxation of blood vessels. Vessel grafts from de nerved murine aortas and porcine middle cerebral arteries were preconditioned using media supplemented with lithium chloride or acetate (0.4-100 mmol/L). Native or following phenylephrine-induced vasoconstriction, the relaxation capacity of preconditioned vessels was assessed by isometric myography, using acetylcholine to test the endothelium-dependent or sodium nitroprusside to test the endothelium-independent vasorelaxation, respectively. At the 0.4 mmol/L lithium concentration, acetylcholine-induced endothelium-dependent vessel relaxation was slightly increased, however, diminished in a concentration dependent manner in vessel grafts preconditioned with lithium at higher therapeutic and supratherapeutic concentrations (0.8-100 mmol/L). In contrast, endothelium-independent vasorelaxation remained unaltered in preconditioned vessel grafts at any lithium concentration tested. Lithium elicits opposing effects on endothelial functions representing a differential impact on the endothelium within the narrow therapeutic window. Lithium accumulation or overdose reduces endothelium-dependent but not endothelium-independent vasorelaxation. The differentially modified endothelium-dependent vascular response represents an additional mechanism contributing to therapeutic or adverse effects of lithium. PMID- 26875502 TI - Treatment-refractory Tourette Syndrome. AB - Tourette Syndrome (TS) is a complex neurodevelopmental condition marked by tics and frequently associated with psychiatric comorbidities. While most cases are mild and improve with age, some are treatment-refractory. Here, we review strategies for the management of this population. We begin by examining the diagnosis of TS and routine management strategies. We then consider emerging treatments for refractory cases, including deep brain stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and novel pharmacological approaches such as new vesicular monoamine transporter type 2 inhibitors, cannabinoids, and anti-glutamatergic drugs. PMID- 26875503 TI - Massage, a complementary therapy effectively promoting the health and well-being of older people in residential care settings: a review of the literature. AB - AIMS: To explore the potential benefits of massage within daily routine care of the older person in residential care settings. BACKGROUND: Globally, the proportion of people over 65 years is rapidly rising. Increased longevity means older people may experience a rise in physiological and psychological health problems. These issues potentially place an increased demand for quality long term care for the older person. Complementary approaches such as massage appear to be needed in quality residential care. DESIGN: A critical literature review was undertaken. METHODS: A literature review pertaining to massage in the older resident was conducted using a range of online databases. Fourteen studies dated 1993-2012 met the inclusion criteria and were critically evaluated as suitable resources for this review. RESULTS: Evidence suggests massage may be advantageous from client and nursing perspectives. Clients' perceive massage to positively influence factors such as pain, sleep, emotional status and psychosocial health. Evidence also demonstrates massage to benefit the client and organisation by reducing the necessity for restraint and pharmacological intervention. Massage may be incorporated into care provision and adopted by care providers and family members as an additional strategy to enhance quality of life for older people. CONCLUSION: Massage offers a practical activity that can be used to enhance the health and well-being of the older person in residential care. IMPLICATIONS FOR PRACTICE: Massage offers benefit for promoting health and well-being of the older person along with potential increased engagement of family in care provision. Integration of massage into daily care activities of the older person requires ongoing promotion and implementation. PMID- 26875504 TI - Corrigendum: Modulating protein activity using tethered ligands with mutually exclusive binding sites. PMID- 26875505 TI - Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms. AB - Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. SUMMARY: Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (beta = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (beta = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (beta = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly influenced by the presence of the other. PMID- 26875506 TI - Integrity of Literature on Expressed Emotion and Relapse in Patients with Schizophrenia Verified by a p-Curve Analysis. AB - There is growing concern that much published research may have questionable validity due to phenomena such as publication bias and p-hacking. Within the psychiatric literature, the construct of expressed emotion (EE) is widely assumed to be a reliable predictor of relapse across a range of mental illnesses. EE is an index of the family climate, measuring how critical, hostile, and overinvolved a family member is toward a mentally ill patient. No study to date has examined the evidential value of this body of research as a whole. That is to say, although many studies have shown a link between EE and symptom relapse, the integrity of the literature from which this claim is derived has not been tested. In an effort to confirm the integrity of the literature of EE predicting psychiatric relapse in patients with schizophrenia, we conducted a p-curve analysis on all known studies examining EE (using the Camberwell Family Interview) to predict psychiatric relapse over a 9- to 12-month follow-up period. Results suggest that the body of literature on EE is unbiased and has integrity, as there was a significant right skew of p-values, a nonsignificant left skew of p-values, and a nonsignificant test of flatness. We conclude that EE is a robust and valuable predictor of symptom relapse in schizophrenia. PMID- 26875507 TI - The April Effect: A Multimedia Orientation Approach to Improve Rotation Transitions During Pediatric Residency. PMID- 26875508 TI - Parental Predictions and Perceptions Regarding Long-Term Childhood Obesity Related Health Risks. AB - OBJECTIVE: To assess how parents perceive long-term risks for developing obesity related chronic health conditions. METHODS: A Web-based nationally representative survey was administered to 502 US parents with a 5- to 12-year-old child. Parents reported whether their child was most likely to be at a healthy weight or overweight, and the probability that their child would develop hypertension, heart disease, depression, or type 2 diabetes in adulthood. Responses of parents of children with overweight and obesity were compared to those of healthy-weight children using multivariate models. RESULTS: The survey had an overall response rate of 39.2%. The mean (SD) unadjusted parent predicted health risks were 15.4% (17.7%), 11.2% (14.7%), 12.5% (16.2%), and 12.1% (16.1%) for hypertension, heart disease, depression, and diabetes, respectively. Despite underperceiving their child's current body mass index class, parents of children with obesity estimate their children to be at greater risk for obesity-related health conditions than parents of healthy-weight children by 5 to 6 percentage points. Having a family history of a chronic disease, higher quality of care, and older parent age were also significant predictors of estimating higher risk probabilities. CONCLUSIONS: Despite evidence that parents of children who are overweight may not perceive these children as being overweight, parents unexpectedly estimate greater future risk of weight-related health conditions for these children. Focusing communication about weight on screening for and reducing the risk of weight related diseases may prove useful in engaging parents and children in weight management. PMID- 26875509 TI - Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites. AB - BACKGROUND: Merkel cell carcinoma is a rare, aggressive neurocutaneous malignancy. This study investigated whether patients with Merkel cell carcinoma in the head and neck had poorer outcomes than patients with Merkel cell carcinoma located elsewhere. METHODS: A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montreal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method. RESULTS: Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis. CONCLUSION: Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy. PMID- 26875510 TI - Correlation between microbiota and growth in Mangrove Killifish (Kryptolebias marmoratus) and Atlantic cod (Gadus morhua). AB - The vertebrate gut is host to large communities of bacteria, and one of the beneficial contributions of this commensal gut microbiota is the increased nutritional gain from feed components that the host cannot degrade on its own. Fish larvae of similar age and under the same rearing conditions often diverge with regards to growth. The underlying reasons for this could be differences in genetic background, feeding behavior or digestive capacity. Both feeding behavior and digestion can be influenced by differences in the microbiota. To investigate possible correlations between the size of fish larvae and their gut microbiota, we analyzed the microbiota small and large genetically homogenous killifish and genetically heterogeneous cod larvae by Bray-Curtis Similarity measures of 16S DNA DGGE patterns. A significant difference in richness (p = 0.037) was observed in the gut microbiota of small and large killifish, but the overall gut microbiota was not found to be significantly different (p = 0.13), indicating strong genetic host selection on microbiota composition at the time of sampling. The microbiota of small and large cod larvae was significantly different with regards to evenness and diversity (p = 0.0001), and a strong correlation between microbiota and growth was observed. PMID- 26875511 TI - Cervical nodal metastases from head and neck squamous cell carcinoma: MRI criteria for treatment assessment. AB - BACKGROUND: The purpose of this study was to assess MRI criteria for detecting residual malignant head and neck squamous cell carcinoma (HNSCC) nodes after chemoradiotherapy (CRT). METHODS: One hundred and six metastatic nodes were assessed 6 weeks posttreatment by MRI for necrosis, extranodal neoplastic spread (ENS), size, and percentage of size change. Size measurements were reanalyzed after dividing posttreatment nodes into "discrete solid," "discrete necrotic," and "indiscrete" groups. Results were correlated with nodal response at 2 years. RESULTS: Eighty-three residual nodes were benign and 23 were malignant. Significant predictors of outcome were percentage of change in solid volume (total-necrotic volume; p = .0002) for all posttreatment nodes and percentage of change in total volume for "discrete solid" posttreatment nodes (p = .0003), the latter showing a <=78% reduction of predicted residual malignant nodes with a negative predictive value (NPV) of 98.2% and positive predictive value (PPV) of 60%. Necrosis, ENS, and size of "discrete necrotic" and "indiscrete" nodes were not significant criteria. CONCLUSION: Necrosis and ENS were inaccurate criteria for residual malignant nodes and hindered the accuracy of size measurements. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1598-E1604, 2016. PMID- 26875512 TI - Malposition of epicardial left atrial appendage occlusion device proved by CT study. PMID- 26875513 TI - Predictors of incipient dysfunction of all cardiac chambers after treatment of metastatic renal cell carcinoma by tyrosine kinase inhibitors. AB - PURPOSE: We aimed to explore the hypothesis that early subclinical cardiac chamber dysfunction secondary to tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma could be signaled by abnormal cardiac mechanics demonstrated by velocity vector imaging. METHODS: Echocardiographic images were acquired from the apical views in 23 metastatic renal cell carcinoma patients. All patients had baseline and at least a 3-month follow-up echocardiogram after receiving TKI therapy. Subendocardial borders of all the cardiac chambers were traced to obtain volumetric and deformation indices. RESULTS: Mean age was 67 +/- 9 years with 92% men. The right ventricle peak systolic global longitudinal strain (GLE) and strain rate were significantly lower after TKIs (-23.49 +/- 5.1 versus -19.81 +/- 5.5, p = 0.002 and -1.52 +/- 0.52 versus -1.24 +/- 0.35 p = 0.02, respectively). LV GLE was not statistically different. Volumetric and deformation indices showed a minimal decrease of the right atrium reservoir and conduit functions, and no significant changes of left atrial function. CONCLUSIONS: The right heart exhibited greater strain changes than the left heart after TKI treatment. The implications of these findings and their potential significance warrant further work. PMID- 26875514 TI - Endocrine assessment of ovarian cycle activity in wild female mountain gorillas (Gorilla beringei beringei). AB - Variability of fertility (i.e. number of births per female per year) has been reported in females of many primate species but only a few studies have explored the associated physiological and behavioral patterns. To investigate the proximate mechanisms of variability in fertility of wild female mountain gorillas (Gorilla beringei beringei), we quantified the occurrence of ovulation, matings, and successful pregnancies among females. We examined the profiles of immunoreactive pregnanediol-3-glucuronide (iPdG) for sixteen females (seven nulliparous and nine parous females, including one geriatric female; average sampling period for fecal sample collection and behavioral observations per female=175 days; SD=94 days, range=66-358 days) monitored by the staff of the Dian Fossey Gorilla Fund's Karisoke Research Center in Parc National des Volcans, Rwanda. We quantified ovarian cycles from iPdG profiles using an algorithm that we developed by adjusting the method of Kassam et al. (1996) to the characteristics of ovarian cycle profiles based on fecal hormone measurements. The mean length of ovarian cycles was 29+/-4 days (median: 28 days, N=13 cycles), similar to ovarian cycle lengths of other great apes and humans. As expected, we found that female mountain gorillas exhibit longer follicular phases (mean+/-SD: 21+/-3 days, N=13 cycles) than luteal phases (mean+/-SD: 8+/-3 days, N=13 cycles). We also found that the frequency of ovarian cycles was greater in parous females (i.e. 20 ovarian cycles across 44 periods of 28 days; 45.5%) than in nulliparous females (i.e. two ovarian cycles across 34 periods of 28 days; 6%). However, the frequency of days on which matings were observed did not differ significantly between parous and nulliparous females, nor between pregnant and non-pregnant females. Five pregnancies were detected with iPdG levels, but only three resulted in live births, indicating miscarriages of the other two. In sum, this study provides information on the underlying endocrine patterns of variation in fertility depending on parity, mating behavior, and pregnancy success in a critically endangered great ape. PMID- 26875515 TI - Influence of exposure in ovo to different light wavelengths on the lateralization of social response in zebrafish larvae. AB - Exposure of the chick embryo to different wavelengths of light of the same intensity has shown that only certain wavelengths may be important in generating visual asymmetries. This study aimed to detect the possible influence of different wavelengths of light on development of asymmetry of social recognition in zebrafish larvae, tested using the fish's mirror image as the stimulus. From fertilization until day 10 post-hatching zebrafish were kept in five different lighting conditions: natural light/dark (LD) cycle, complete darkness (DD), and artificial LD cycles with 14 h of monochromatic light (red, green, or violet light) and 10 h of darkness (rLD 14:10, gLD 14:10, vLD 14:10, respectively). On day 10 after hatching, the zebrafish larvae were subjected to a mirror test. A preference for using the left eye to scrutinize their mirror image was apparent only in zebrafish larvae exposed to and reared under a natural LD cycle, and not following exposure to any of other lighting conditions. These results are discussed with reference to other evidence of brain lateralization. PMID- 26875516 TI - Catestatin and GABA(A)R related feeding habits rely on dopamine, ghrelin plus leptin neuroreceptor expression variations. AB - Catestatin (CST), an endogenously small sympathoinhibitory peptide is capable of interfering with the major cerebral neuroreceptor-blocking site, i.e. gamma aminobutyric acidA receptor (GABAAR) system especially in limbic brain areas that are involved with feeding behaviors. The GABAARergic-related effects seem to derive from its interaction with other molecular neuroreceptors such as dopaminergic, ghrelin and leptinergic. In this context, the present study aimed to investigate probable feeding responses (eating and drinking) induced by treatment with CST and the GABAAR antagonist bicucullin (BIC) alone or simultaneously (CST+BIC) in the Syrian hibernating hamster (Mesocricetus auratus) model. Hamsters that received these compounds via intracerebroventricular infusions displayed notable variations of feeding and drinking bouts. In particular, an anorexigenic response was evident following treatment with CST while BIC evoked a significant increase of eating and drinking behaviors. Surprisingly when both agents were given simultaneously, a predominating anorexigenic response was detected as shown by evident CST-dependent reduction of feeding bouts. Contextually such behaviors, especially those following the combined treatment were tightly correlated with the significantly increased cerebral dopamine receptor 1 (D1) plus reduced ghrelin receptor (GhsR) and leptin receptor (LepR) transcript levels. Overall, the anorexigenic effect of CST deriving from its tight interaction with GABAARs activity plus D1 and GhsR transcripts tends to propose these neuronal elements as pivotal factors responsible for feeding disorders. PMID- 26875517 TI - European public health policies for managing contacts of invasive meningococcal disease cases better harmonised in 2013 than in 2007. AB - In 2007, a European survey identified variation in country policies on public health management of invasive meningococcal disease (IMD). In 2009-10, the European Centre for Disease Prevention and Control (ECDC) published evidence based guidance on IMD. We therefore surveyed again European countries to describe policies for managing IMD cases and contacts in 2013. We asked national IMD public health experts from 32 European countries to complete a questionnaire focusing on post-exposure prophylaxis (PEP) for IMD contacts and meningococcal vaccination. Proportions in 2007 and 2013 were compared using the chi-squared test. All 32 countries responded, with responses from two regions for Belgium and Italy; half stated having used ECDC guidance to update national recommendations. PEP was recommended to close contacts in 33 of 34 countries/regions, mainly ciprofloxacin for adults (29/32 countries) and rifampicin for children (29/32 countries). ECDC guidance for managing IMD contacts in airplanes was strictly followed by five countries/regions. Twenty-three countries/regions participated in both surveys. Compared with 2007, in 2013, more countries/regions recommended i) ceftriaxone for children (15/23 vs 6/20; p = 0.03), ii) PEP for all children in the same preschool group (8/23 vs 17/23; p = 0.02). More countries/regions recommended evidence-based measures for IMD public health management in 2013 than 2007. However, some discrepancies remain and they call for further harmonisation. PMID- 26875518 TI - Serum gamma-glutamyltransferase and Mortality due to Cardiovascular Disease in Japanese Men and Women. AB - AIM: Whether the association between serum gamma-glutamyltransferase (gamma-GTP) levels and total cardiovascular disease (CVD) mortality is independent of alcohol drinking in East Asian populations is not well known. We conducted a pooled analysis of Japanese men and women that enabled an analysis restricted to never drinkers. METHODS: A total of 15,987 men and 25,053 women aged 40-79 years, pooled from seven cohort studies throughout Japan, were followed-up to examine sex-specific relationship between serum gamma-GTP levels and total CVD mortality. Cox regression model was used that was adjusted for age, smoking status, body mass index, and systolic blood pressure and serum triglyceride, total cholesterol, aspartate aminotransferase, and alanine aminotransferase levels. RESULTS: During an average follow-up of 8.7 years, we documented 361 and 340 deaths from total CVD, 146 and 168 from stroke, and 101 and 53 from coronary heart disease (CHD) for men and women, respectively. Among the never-drinkers, hazard ratios (HRs) for mortality for one standard deviation of log-gamma-GTP for men were 1.89 (1.00-3.58) for stroke, 1.04 (0.57-1.90) for CHD, and 1.43 (1.04 1.96) for total CVD. For women, HRs were 1.28 (1.06-1.54), 1.81 (1.34-2.44), and 1.30 (1.14-1.49), respectively. CONCLUSION: gamma-GTP may be a risk factor for total CVD mortality independent of alcohol drinking status in Japanese men and women. PMID- 26875519 TI - Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction. AB - AIM: To analyse the relationship between two potentially functional single nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910164 and rs57095329) and the risk of atherosclerotic cerebral infarction (ACI). METHODS: A total of 297 patients with ACI and 300 matched healthy individuals were enrolled in the study. The miR-146a polymorphism was detected using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: A significant difference in the C allele frequency at rs2910164 (p=0.028) was noted between patients with ACI and control subjects. In contrast, the genotype and allele frequencies of rs57095329 were not statistically associated with ACI. In addition, the decreased expression of miR-146a was significantly more frequent in ACI patients who were ApoEepsilon4 (+) carriers (p=0.0233), and rs2910164 G>C was intimately associated with the ApoEepsilon4-containing genotype in patients compared with the ApoEepsilon4 (-) carriers (p=0.0323). CONCLUSIONS: Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoEepsilon4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR-146a and ApoEepsilon4 in the development of ACI, with potentially important therapeutic implications. PMID- 26875520 TI - A Proposal for the Optimal Management Target for Serum Non-High-Density Lipoprotein Cholesterol Level in Low-Risk Japanese Workers. AB - AIM: The Japan Atherosclerosis Society Guidelines for the Diagnosis and Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JAS Guidelines 2012) indicate that the management target for serum non-high-density lipoprotein cholesterol (non-HDLC) level is 30 mg/dL higher than that for low-density lipoprotein cholesterol (LDLC) level. However, it remains unclear whether this value is applicable to subjects at a low risk of cardiovascular disease. This study aimed to propose the optimal management target for serum non-HDLC level in low-risk Japanese subjects. METHODS: Among 20,909 subjects who underwent annual medical checkup at a Japanese company in 2008, we analyzed the data of 17,023 subjects (14,352 men, mean age 37.8+/-8.6 years) in risk category I according to the JAS Guidelines 2012. The correlation between LDLC and non-HDLC levels was examined. RESULTS: A strong correlation was found between LDLC and non-HDLC levels (r=0.95, p<0.001). The following regression equation for calculation of non-HDLC was obtained from linear regression analysis: non-HDLC (mg/dL)=1.09*LDLC (mg/dL)+7.79. According to this equation, the optimal management target for non HDLC level corresponding to that for LDLC level (160 mg/dL) was 180 mg/dL. A multiple logistic regression analysis revealed that age, obesity, habitual alcohol intake, and current smoking were significantly associated with non-HDLC >=180 mg/dL. CONCLUSIONS: The management target for non-HDLC level is recommended to be set at 20 mg/dL higher than that for the LDLC level (i.e., 180 mg/dL) in low-risk Japanese subjects. PMID- 26875521 TI - Management of Familial Hypercholesterolemia in Hong Kong. AB - Familial hypercholesterolemia (FH) is an autosomal-dominant genetic disease characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic coronary heart disease (CHD). Patients with FH in Hong Kong were found by the identification of potential probands with primary hypercholesterolemia manifesting total cholesterol levels greater than 7.5 mmol/L or LDL-C levels greater than 4.9 mmol/L and undertaking cascade screening of available relatives in the Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong since the early 1990s. Our previous study in a group of 252 subjects from 87 pedigrees clinically diagnosed as having heterozygous FH reported the mean plasma LDL-C level as 7.2+/-1.5 mmol/L. Xanthomata were present in 40.6% of males and 54.8% of females. The prevalence of known CHD was relatively low at 9.9% in males and 8.5% in females. All FH patients were offered treatment with statins and many of them reached the LDL-C goal with a moderate or high dose of potent statin alone. Ezetimibe is usually added for patients who have not achieved target LDL-C levels on statin alone, particularly in patients with established CHD. Some FH patients who have not achieved the LDL-C targets with this combination have entered into clinical trials with new cholesterol-modifying agents such as the monoclonal antibodies to proprotein convertase subtilisin kexin type 9. Increased awareness, early identification, and optimal treatment are essential to reduce the risk of CHD, increase life expectancy, and improve the quality of life of patients with FH. PMID- 26875522 TI - Temporal Trends in Clinical Outcomes Following Percutaneous Coronary Intervention in Patients with Renal Insufficiency. AB - AIM: Renal insufficiency is associated with worse clinical outcomes in patients with coronary artery disease. Since the introduction of percutaneous coronary intervention (PCI), the revascularization therapy has evolved with advances of devices, improvements in operator techniques, and the establishment of medical therapy. We examined temporal trends of the clinical outcomes following PCI in patients with renal insufficiency. METHODS: Patients with renal insufficiency after PCI at Juntendo University across three eras (plain balloon angioplasty, bare metal stent (BMS), and drug-eluting stent (DES)) were examined in this study. The primary endpoint was a composite of all-cause mortality, nonfatal acute coronary syndrome, nonfatal stroke, and repeat revascularization within 3 years after the index revascularization. RESULTS: A total of 1,420 patients were examined. Baseline characteristics have become unfavorable over time, whereas administration rate of medications for secondary prevention has increased. The event-free survival rates for the endpoint were different among the groups. Adjusted relative risk reduction for the endpoint was 35% and 51% in the BMS and DES eras (using the plain angioplasty era as reference). The adjusted relative risk reduction of the DES era was 26% compared with that of the BMS era. CONCLUSIONS: The incidence of cardiovascular events after PCI has reduced during the 26-year period mainly because of the reduction in repeat revascularization in patients with renal insufficiency, despite the higher risk profiles in the recent era. PMID- 26875523 TI - Optimal Management Target for Non-High-Density Lipoprotein Cholesterol. PMID- 26875524 TI - Constructing modular and universal single molecule tension sensor using protein G to study mechano-sensitive receptors. AB - Recently a variety of molecular force sensors have been developed to study cellular forces acting through single mechano-sensitive receptors. A common strategy adopted is to attach ligand molecules on a surface through engineered molecular tethers which report cell-exerted tension on receptor-ligand bonds. This approach generally requires chemical conjugation of the ligand to the force reporting tether which can be time-consuming and labor-intensive. Moreover, ligand-tether conjugation can severely reduce the activity of protein ligands. To address this problem, we developed a Protein G (ProG)-based force sensor in which force-reporting tethers are conjugated to ProG instead of ligands. A recombinant ligand fused with IgG-Fc is conveniently assembled with the force sensor through ProG:Fc binding, therefore avoiding ligand conjugation and purification processes. Using this approach, we determined that molecular tension on E cadherin is lower than dsDNA unzipping force (nominal value: 12 pN) during initial cadherin-mediated cell adhesion, followed by an escalation to forces higher than 43 pN (nominal value). This approach is highly modular and potentially universal as we demonstrate using two additional receptor-ligand interactions, P-selectin &PSGL-1 and Notch &DLL1. PMID- 26875525 TI - Correlation between topological band character and chemical bonding in a Bi14Rh3I9-based family of insulators. AB - Recently the presence of topologically protected edge-states in Bi14Rh3I9 was confirmed by scanning tunnelling microscopy consolidating this compound as a weak 3D topological insulator (TI). Here, we present a density-functional-theory-based study on a family of TIs derived from the Bi14Rh3I9 parent structure via substitution of Ru, Pd, Os, Ir and Pt for Rh. Comparative analysis of the band structures throughout the entire series is done by means of a unified minimalistic tight-binding model that evinces strong similarity between the quantum-spin-Hall (QSH) layer in Bi14Rh3I9 and graphene in terms of Pz-molecular orbitals. Topologically non-trivial energy gaps are found for the Ir-, Rh-, Pt- and Pd-based systems, whereas the Os- and Ru-systems remain trivial. Furthermore, the energy position of the metal d-band centre is identified as the parameter which governs the evolution of the topological character of the band structure through the whole family of TIs. The d-band position is shown to correlate with the chemical bonding within the QSH layers, thus revealing how the chemical nature of the constituents affects the topological band character. PMID- 26875526 TI - Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens. AB - Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d-alpha-galactosylceramide (alpha-GalCer) reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18 TRBV25-1(+) type I NKT cell repertoire. These cells express a range of TCR alpha- and beta-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7-8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A'-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with alpha-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d-alpha-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition. PMID- 26875528 TI - Stable neutral radicals of planar N2O2-type dipyrrin platinum complexes: hybrid radicals of the delocalized organic pi-orbital and platinum d-orbital. AB - Neutral radicals of N2O2-dipyrrin platinum complexes were synthesized by the reaction of dipyrrin ligands with PtCl2(cod) and successive one-electron oxidation. The radicals are very stable even under aerobic and ambient conditions. X-ray crystallographic analysis revealed the stacking array of the planar dipyrrin complex moieties. The ESR signals were broadened and significantly downfield shifted. The absorption spectra exhibited NIR bands. These results indicated a delocalized radical character with a contribution by the platinum d-orbital. PMID- 26875527 TI - Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats. AB - Perinatal hypoxic-ischemic encephalopathy (HIE) is associated with high neonatal mortality and severe long-term neurologic morbidity. Yet the mechanisms of brain injury in infants with HIE remain largely elusive. The present study determined a novel mechanism of microRNA-210 (miR-210) in silencing endogenous neuroprotection and increasing hypoxic-ischemic brain injury in neonatal rats. The study further revealed a potential therapeutic effect of miR-210 inhibition using complementary locked nucleic acid oligonucleotides (miR-210-LNA) in 10-day-old neonatal rats in the Rice-Vannucci model. The underlying mechanisms were investigated with intracerebroventricular injection (i.c.v) of miR-210 mimic, miR-210-LNA, glucocorticoid receptor (GR) agonist and antagonist. Luciferase reporter gene assay was conducted for identification of miR-210 targeting GR 3'untranslated region. The results showed that the HI treatment significantly increased miR-210 levels in the brain, and miR-210 mimic significantly decreased GR protein abundance and exacerbated HI brain injury in the pups. MiR-210-LNA administration via i.c.v. 4h after the HI insult significantly decreased brain miR-210 levels, increased GR protein abundance, reduced HI-induced neuronal death and brain infarct size, and improved long-term neurological function recovery. Of importance, the intranasal delivery of miR-210-LNA 4h after the HI insult produced similar effects in decreasing HI-induced neonatal brain injury and improving neurological function later in life. Altogether, the present study provides evidence of a novel mechanism of miR-210 in a neonatal HI brain injury model, and suggests a potential therapeutic approach of miR-210 inhibition in the treatment of neonatal HIE. PMID- 26875529 TI - Effects of fragment traits, burial orientation and nutrient supply on survival and growth in Populus deltoides * P. simonii. AB - Clonal propagations of shoot or root fragments play pivotal roles in adaptation of clonal trees to environmental heterogeneity, i.e. soil nutrient heterogeneity and burials after disturbance. However, little is known about whether burial orientation and nutrient supply can alter the effects of fragment traits in Populus. Shoot and root fragments of Populus deltoides * P. simonii were subjected to burials in two different fragment diameters (0.5 and 2.0 cm), two fragment lengths (5 and 15 cm) and three burial orientations (horizontal, upward and downward). For the shoot fragments, survival and growth were significantly higher in the larger pieces (either in length or diameter) and the horizontal/upward burial position. On the contrary, the effect of burial position was reversed for the root fragments. Shoot/root fragments of 15 cm in length in horizontal burial position were then subjected to two different fragment diameters (0.5 and 2.0 cm) and four types of nutrient supplies (without nutrient, low frequency, high frequency and patchy). Growth of shoot fragments of 2.0 cm in diameter significantly increased in high frequency and patchy nutrient supplies than that of without nutrient treatment. These results suggest that burial orientation and nutrient supply could be employed in clonal propagations of cuttings, afforestation or regeneration in Populus. PMID- 26875530 TI - Modeling Non-Heme Iron Halogenases: High-Spin Oxoiron(IV)-Halide Complexes That Halogenate C-H Bonds. AB - The non-heme iron halogenases CytC3 and SyrB2 catalyze C-H bond halogenation in the biosynthesis of some natural products via S = 2 oxoiron(IV)-halide intermediates. These oxidants abstract a hydrogen atom from a substrate C-H bond to generate an alkyl radical that reacts with the bound halide to form a C-X bond chemoselectively. The origin of this selectivity has been explored in biological systems but has not yet been investigated with synthetic models. Here we report the characterization of S = 2 [Fe(IV)(O)(TQA)(Cl/Br)](+) (TQA = tris(quinolyl-2 methyl)amine) complexes that can preferentially halogenate cyclohexane. These are the first synthetic oxoiron(IV)-halide complexes that serve as spectroscopic and functional models for the halogenase intermediates. Interestingly, the nascent substrate radicals generated by these synthetic complexes are not as short-lived as those obtained from heme-based oxidants and can be intercepted by O2 to prevent halogenation, supporting an emerging notion that rapid rebound may not necessarily occur in non-heme oxoiron(IV) oxidations. PMID- 26875532 TI - Liquid biopsy: Potential and challenges. PMID- 26875533 TI - Successful treatment of pachydermoperiostosis with etoricoxib in a patient with a homozygous splice-site mutation in the SLCO2A1 gene. AB - Pachydermoperiostosis (PDP), also named primary hypertrophic osteoarthropathy (PHO: MIM 167100), is a rare genetic disease characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and digital clubbing. Additional clinical signs and symptoms include seborrheic hyperplasia, hyperhidrosis, and arthropathy. This article is protected by copyright. All rights reserved. PMID- 26875531 TI - Availability: A Metric for Nucleic Acid Strand Displacement Systems. AB - DNA strand displacement systems have transformative potential in synthetic biology. While powerful examples have been reported in DNA nanotechnology, such systems are plagued by leakage, which limits network stability, sensitivity, and scalability. An approach to mitigate leakage in DNA nanotechnology, which is applicable to synthetic biology, is to introduce mismatches to complementary fuel sequences at key locations. However, this method overlooks nuances in the secondary structure of the fuel and substrate that impact the leakage reaction kinetics in strand displacement systems. In an effort to quantify the impact of secondary structure on leakage, we introduce the concepts of availability and mutual availability and demonstrate their utility for network analysis. Our approach exposes vulnerable locations on the substrate and quantifies the secondary structure of fuel strands. Using these concepts, a 4-fold reduction in leakage has been achieved. The result is a rational design process that efficiently suppresses leakage and provides new insight into dynamic nucleic acid networks. PMID- 26875534 TI - Biomimetic interconnected porous keratin-fibrin-gelatin 3D sponge for tissue engineering application. AB - The medicated wound dressing material with highly interconnected pores, mimicking the function of the extracellular matrix was fabricated for the promotion of cell growth. In this study, keratin (K), fibrin (F) and gelatin (G) composite scaffold (KFG-SPG) was fabricated by freeze drying technique and the mupirocin (D) drug was successfully incorporated with KFG-SPG (KFG-SPG-D) intended for tissue engineering applications. The fabrication of scaffold was performed without the use of any strong chemical solvents, and the solid sponge scaffold was obtained with well interconnected pores. The porous morphology of the scaffold was confirmed by SEM analysis and exhibited competent mechanical properties. KFG-SPG and KFG-SPG-D possess high level of biocompatibility, cell proliferation and cell adhesion of NIH 3T3 fibroblast and human keratinocytes (HaCaT) cell lines thereby indicating the scaffolds potential as a suitable medicated dressing for wound healing. PMID- 26875536 TI - Mutagenesis for improvement of activity and thermostability of amylomaltase from Corynebacterium glutamicum. AB - This work aims to improve thermostability of amylomaltase from a mesophilic Corynebacterium glutamicum (CgAM) by random and site-directed mutagenesis. From error prone PCR, a mutated CgAM with higher thermostability at 50 degrees C compared to the wild-type was selected and sequenced. The result showed that the mutant contains a single mutation of A406V. Site-directed mutagenesis was then performed to construct A406V and A406L. Both mutated CgAMs showed higher intermolecular transglucosylation activity with an upward shift in the optimum temperature and a slight increase in the optimum pH for disproportionation and cyclization reactions. Thermostability of both mutated CgAMs at 35-40 degrees C was significantly increased with a higher peak temperature from DSC spectra when compared to the wild-type. A406V had a greater effect on activity and thermostability than A406L. The catalytic efficiency values kcat/Km of A406V- and A406L-CgAMs were 2.9 and 1.4 times higher than that of the wild-type, respectively, mainly due to a significant increase in kcat. LR-CD product analysis demonstrated that A406V gave higher product yield, especially at longer incubation time and higher temperature, in comparison to the wild-type enzyme. PMID- 26875535 TI - Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine. AB - Adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. Thus, adjuvants are important for vaccine research. Polysaccharides isolated from select Chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. In the present study, the polysaccharides IIP-A-1 and IIP-2 were isolated from Isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administration of inactivated rabies virus rCVS-11-G into mice. Blood was collected to determine virus neutralizing antibody (VNA) titers and B and T lymphocyte activation status. Inguinal lymph node samples were collected and used to measure B lymphocyte proliferation. Splenocytes were isolated, from which antigen-specific cellular immune responses were detected via ELISpot, ELISA and intracellular cytokine staining. The results revealed that both types of polysaccharides induce more rapid changes and higher VNA titers than aluminum hydroxide. Flow cytometry assays revealed that the polysaccharides activated more B lymphocytes in the lymph nodes and more B and T lymphocytes in the blood than aluminum hydroxide. Antigen-specific cellular immune responses showed that IIP-2 strongly induced T lymphocyte proliferation in the spleen and high levels of cytokine secretion from splenocytes, whereas aluminum hydroxide induced proliferation in only a small number of lymphocytes and the secretion of only small quantities of cytokines. Collectively, these data suggest that the polysaccharide IIP-2 exhibits excellent adjuvant activity and can enhance both cellular and humoral immunity. PMID- 26875537 TI - Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line. AB - Successful gene therapy requires the development of suitable vehicles for the selective and efficient delivery of genes to specific target cells at the expense of minimal toxicity. In this work, we investigated a non-viral gene delivery system based on chitosan (CS) to specifically address cystic fibrosis (CF). Thus, electrostatic self-assembled CS-pEGFP and CS-pEGFP-siRNA complexes were prepared from high-pure fully characterized CS (Mw ~ 20 kDa and degree of acetylation ~ 30%). The average diameter of positively-charged complexes (i.e. zeta ~+25 mV) was ~ 200 nm. The complexes were found relatively stable over 14h in Opti-MEM. Cell viability study did not show any significant cytotoxic effect of the CS based complexes in a human bronchial cystic fibrosis cell line (CFBE41o-). We evaluated the transfection efficiency of this cell line with both CS-pEGFP and co transfected with CS-pEGFP-siRNA complexes at (N/P) charge ratio of 12. We reported an increase in the fluorescence intensity of CS-pEGFP and a reduction in the cells co-transfected with CS-pEGFP-siRNA. This study shows proof-of-principle that co-transfection with chitosan might be an effective delivery system in a human CF cell line. It also offers a potential alternative to further develop therapeutic strategies for inherited disease treatments, such as CF. PMID- 26875538 TI - Vancomycin loaded superparamagnetic MnFe2O4 nanoparticles coated with PEGylated chitosan to enhance antibacterial activity. AB - Increasing prevalence of antibiotic-resistant and failed-treatment make more investigations to deal with these problems. Hence new therapeutic approaches for effective treatment are necessary. Ferrite superparamagnetic nanoparticles have potentially antibacterial activity. In this study we prepared MnFe2O4 superparamagnetic nanoparticles as core by precipitation method and used chitosan crosslinked by glutaraldehyde as shell, then modified with PEG to increase stability of particles against RES. Chitosan coating not only improves the properties of ferrit nanoparticles but also has antibacterial activity. FT-IR confirmed this surface modification; XRD and SEM were developed to demonstrate particle size approximately 25 nm and characteristics of crystal structure of these nanoparticles. Magnetic properties of nanoparticles were evaluated by VSM. Actual drug loading and releasing were examined by UV-vis spectroscopy method. We employed liquid broth dilution method to assessment antibacterial activity of nanoparticles against microorganisms. Significant antibacterial effect against gram negative bacteria was developed. PMID- 26875539 TI - Effect of dietary net energy concentration on dry matter intake and energy partition in cows in mid-lactation under heat stress. AB - This study aimed to determine the net energy requirement of Holstein cows in mid lactation under heat stress. Twenty-five multiparous Holstein cows were randomly allocated to five groups corresponding to five isonitrogenous total mixed rations, with net energy for lactation (NEL ) content of 6.15 (NE-6.15), 6.36 (NE 6.36), 6.64 (NE-6.64), 6.95 (NE-6.95), 7.36 (NE-7.36) MJ/kg of dry matter (DM), respectively. Throughout the experimental period the average temperature humidity index at 07.00, 14.00 and 22.00 hours was 72.1, 88.7, and 77.6, respectively. DM intake decreased significantly with the elevated dietary NEL concentration. Fat corrected milk increased quadratically, and milk fat content and milk energy (MJ/kg) reached the greatest in the NE-6.95 group with increasing dietary NEL content. Strong correlations were found between dietary NEL content and: (i) DM intake; (ii) NEL intake; (iii) milk energy (El ); (iv) El /metabolizable energy intake (MEI); (v) El /NEL intake, as well as between NEL intake and fat corrected milk yield (FCM). The suitable net energy required for dairy cows producing 1 kg FCM ranged from 5.01 to 5.03 MJ, was concluded from the above-stated regressions. Correlation between heat production (HP) and MEI could be expressed as: Log (HP) = -0.4304 + 0.2963*MEI (n = 15, R2 = 0.99, Root Mean Square Error (RMSE) = 0.18). Fasting HP was 0.3712 MJ/kg0.75 when extrapolating MEI to zero. PMID- 26875541 TI - Ampere Hour as a Predictor of Cardiac Resynchronization Defibrillator Pulse Generator Battery Longevity: A Multicenter Study. AB - BACKGROUND: Cardiac resynchronization defibrillator (CRT-D) devices improve survival for New York Heart Association classes II-IV systolic heart failure patients with QRS > 120 ms and left ventricular ejection fraction < 35%. A limitation of 100% CRT pacing is excess battery depletion and pulse generator (PG) replacement compared to VVI or dual-chamber systems. Ampere hour (Ah) measures PG battery capacity and may predict CRT-D device longevity. METHODS: We performed a multicenter retrospective study of all CRT-D devices implanted at our centers from August 1, 2008 to December 31, 2010. Analysis was performed for survival to elective replacement indicator (ERI) between 1.0 Ah, 1.4 Ah, and 2.0 Ah devices, per manufacturers' specifications. RESULTS: One thousand three hundred and two patients were studied through December 31, 2014. Patients were followed for an average of 3.0 +/- 1.3 years (794 1.0 Ah, 322 2.0 Ah, and 186 1.4 Ah devices under study). CRT-D generator ERI occurred in 13.5% of 1.0 Ah systems (107 out of 794), versus 3.8% in 1.4 Ah (seven out of 186), and 0.3% in 2.0 Ah devices (one out of 322) over mean follow-up of 3.0 years. Odds ratio (OR) for reaching ERI with 1.0 Ah device versus 1.4 Ah or 2.0 Ah was 9.73, P < 0.0001. Univariate predictors for ERI included 1.0 Ah device and LV pacing output >3V @ 1 ms (OR: 3.74, P < 0.001). LV impedance >1,000 ohms predicted improved device survival (OR: 0.38, P = 0.0025). CONCLUSIONS: CRT-D battery capacity measured by Ah is a strong predictor of survival to ERI for modern systems. Further study on cost and morbidity associated with early PG change in 1.0 Ah systems is warranted. PMID- 26875540 TI - Oral tofacitinib efficacy, safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized, double blind, phase 3 study. AB - Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open-label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of "clear" or "almost clear" (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty-seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies. PMID- 26875542 TI - In situ growth of carbon nanotube wrapped Si composites as anodes for high performance lithium ion batteries. AB - The composites of carbon nanotube wrapped Si particles (CNTWS) were synthesized in situ by using the catalytic chemical vapor deposition (CCVD) method. In this process, carbon nanotubes were produced in situ to wrap Si by the catalysis action of nascent Cu* under an acetylene atmosphere at a relatively low temperature of 400 degrees C, in which nascent Cu* was created by the reaction between Si particles and CuCl synchronously. The weight ratio of Si/C in CNTWS is 0.76/0.24. As anode materials for lithium ion batteries, the CNTWS composites exhibit a reversible discharge capacity of 1031.1 mA h g(-1) at 1.8 A g(-1) after 500 cycles, and 868.2 mA h g(-1) at 10.0 A g(-1). The high electrochemical performance of CNTWS composites is associated with the in situ formed carbon nanotubes. PMID- 26875543 TI - Retrograde trafficking from the endosome to the trans-Golgi network mediated by the retromer is required for fungal development and pathogenicity in Fusarium graminearum. AB - In eukaryotes, the retromer is an endosome-localized complex involved in protein retrograde transport. However, the role of such intracellular trafficking events in pathogenic fungal development and pathogenicity remains unclear. The role of the retromer complex in Fusarium graminearum was investigated using cell biological and genetic methods. We observed the retromer core component FgVps35 (Vacuolar Protein Sorting 35) in the cytoplasm as fast-moving puncta. FgVps35-GFP co-localized with both early and late endosomes, and associated with the trans Golgi network (TGN), suggesting that FgVps35 functions at the donor endosome membrane to mediate TGN trafficking. Disruption of microtubules with nocodazole significantly restricted the transportation of FgVps35-GFP and resulted in severe germination and growth defects. Mutation of FgVPS35 not only mimicked growth defects induced by pharmacological treatment, but also affected conidiation, ascospore formation and pathogenicity. Using yeast two-hybrid assays, we determined the interactions among FgVps35, FgVps26, FgVps29, FgVps17 and FgVps5 which are analogous to the yeast retromer complex components. Deletion of any one of these genes resulted in similar phenotypic defects to those of the DeltaFgvps35 mutant and disrupted the stability of the complex. Overall, our results provide the first clear evidence of linkage between the retrograde transport mediated by the retromer complex and virulence in F. graminearum. PMID- 26875544 TI - Fast quantifying collision strength index of ethylene-vinyl acetate copolymer coverings on the fields based on near infrared hyperspectral imaging techniques. AB - A novel strategy based on the near infrared hyperspectral imaging techniques and chemometrics were explored for fast quantifying the collision strength index of ethylene-vinyl acetate copolymer (EVAC) coverings on the fields. The reflectance spectral data of EVAC coverings was obtained by using the near infrared hyperspectral meter. The collision analysis equipment was employed to measure the collision intensity of EVAC materials. The preprocessing algorithms were firstly performed before the calibration. The algorithms of random frog and successive projection (SP) were applied to extracting the fingerprint wavebands. A correlation model between the significant spectral curves which reflected the cross-linking attributions of the inner organic molecules and the degree of collision strength was set up by taking advantage of the support vector machine regression (SVMR) approach. The SP-SVMR model attained the residual predictive deviation of 3.074, the square of percentage of correlation coefficient of 93.48% and 93.05% and the root mean square error of 1.963 and 2.091 for the calibration and validation sets, respectively, which exhibited the best forecast performance. The results indicated that the approaches of integrating the near infrared hyperspectral imaging techniques with the chemometrics could be utilized to rapidly determine the degree of collision strength of EVAC. PMID- 26875545 TI - Roles of specific lipid species in the cell and their molecular mechanism. AB - Thousands of different molecular species of lipids are present within a single cell, being involved in modulating the basic processes of life. The vast number of different lipid species can be organized into a number of different lipid classes, which may be defined as a group of lipids with a common chemical structure, such as the headgroup, apart from the nature of the hydrocarbon chains. Each lipid class has unique biological roles. In some cases, a relatively small change in the headgroup chemical structure can result in a drastic change in function. Such phenomena are well documented, and largely understood in terms of specific interactions with proteins. In contrast, there are observations that the entire structural specificity of a lipid molecule, including the hydrocarbon chains, is required for biological activity through specific interactions with membrane proteins. Understanding of these phenomena represents a fundamental change in our thinking of the functions of lipids in biology. There are an increasing number of diverse examples of roles for specific lipids in cellular processes including: Signal transduction; trafficking; morphological changes; cell division. We are gaining knowledge and understanding of the underlying molecular mechanisms. They are of growing importance in both basic and applied sciences. PMID- 26875546 TI - Perspectives of HIV agencies on improving HIV prevention, treatment, and care services in the USA. AB - HIV healthcare services in the USA are made available through a complex funding and delivery system. We present perspectives of HIV agencies on improvements that could lead to an ideal system of HIV prevention, treatment and care. We conducted semi-structured interviews with representatives from 21 HIV agencies offering diverse services in Baltimore, MD. Thematic analysis revealed six key themes: (1) Focusing on HIV prevention, (2) Establishing common entry-points for services, (3) Improving information availability, (4) Streamlining funding streams, (5) Removing competitiveness and (6) Building trust. We recommend that in addition to addressing operational issues regarding service delivery and patient care, initiatives to improve HIV service systems should address underlying social issues such as building trust. PMID- 26875547 TI - Blockade of cell adhesion molecules enhances cell engraftment in a murine model of liver cell transplantation. AB - AIM: OLT is the best alternative for patients with end-stage liver diseases. However, as the need for organs surpasses donor availability, alternatives to OLT are required. LCT could be a useful option versus OLT in several patients even though its low cell-engraftment hampers its efficiency. Endothelial cell barrier is the main obstacle for the implantation of cells into the parenchyma. Our study has focused on the modification of the endothelial barrier with monoclonal antibodies against adhesion molecules in order to increase cell engraftment in a mouse model of liver cell transplantation. METHODS: Anti-mouse CD54 and anti mouse CD61 antibodies were administered intrasplenically to healthy mice within 60 min prior to stem cell transplantation. Animals were sacrificed either short term at 2h or middle term seven days after transplantation. Immunohistochemical techniques to detect alkaline phosphatase activity were used to identify the transplanted cells within the liver parenchyma. RESULTS: Anti-CD54 and anti-CD61 administration increases vascular patency and cell engraftment. This represents a 32% and 45% increase, respectively, of engrafted cells compared to the control (p<0.05). CONCLUSION: Modification of the vascular wall with monoclonal antibodies against endothelial adhesion molecules before cell transplantation enhances cell engraftment into the mouse liver. PMID- 26875549 TI - Physical properties modulation of Fe3O4/Pb(ZrTi)O3 heterostructure via Fe diffusion. AB - The manipulation of material properties in perovskite oxide heterojunctions has been increasingly studied, owing to their interacting lattice, charge, spin and orbital degrees of freedom. In this work, the switching, ferroelectricity and magneto-transport properties of epitaxially grown perovskite Pb(Zr0.52Ti0.48)O3 layers sandwiched between Fe3O4 (top electrode) and SrRuO3 (bottom electrode) are investigated. These films show a typical ferroelectric polarization of ~50 MUC/cm(2). Once the Pb(Zr0.52Ti0.48)O3 films become thinner (~30 nm), one can set (reset) the Fe3O4/Pb(Zr0.52Ti0.48)O3/SrRuO3 structures into a low (high) resistance state via formation (rupture) of an Fe-related filament in Pb(Zr0.52Ti0.48)O3 through manipulation of an electric field. Interestingly, at the low-resistance state, a prominent magnetoresistance signal of ~3% was observed. There is no magnetoresistance signal detected in the virgin Pb(Zr0.52Ti0.48)O3 film (before switching), high-resistive state Pb(Zr0.52Ti0.48)O3 film and Au/Pb(Zr0.52Ti0.48)O3/SrRuO3. These phenomena are attributed to the diffusion of Fe-related ions into the Pb(Zr0.52Ti0.48)O3 film, turning a non-magnetic and insulating layer of perovskite Pb(Zr0.52Ti0.48)O3 into a magnetic and semiconducting-like Pb(Zr0.52Ti0.48)O3. The magneto-transport properties of Fe3O4/Pb(Zr0.52Ti0.48)O3/SrRuO3 have been studied extensively. Such resistance-ferroelectric-ferromagnetic coupling in a single compound paves the way to the realization of a non-volatile multiple-state Pb(ZrTi)O3 hybrid memory, as well as new computing approaches. PMID- 26875548 TI - Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE2, PGD2, and HGF. AB - Apoptotic cell clearance results in the release of growth factors and the action of signaling molecules involved in tissue homeostasis maintenance. Here, we investigated whether and how macrophages programmed by apoptotic cells inhibit the TGF-beta1-induced Epithelial-mesenchymal transition (EMT) process in lung alveolar epithelial cells. Treatment with conditioned medium derived from macrophages exposed to apoptotic cells, but not viable or necrotic cells, inhibited TGF-beta1-induced EMT, including loss of E-cadherin, synthesis of N cadherin and alpha-smooth muscle actin, and induction of EMT-activating transcription factors, such as Snail1/2, Zeb1/2, and Twist1. Exposure of macrophages to cyclooxygenase (COX-2) inhibitors (NS-398 and COX-2 siRNA) or RhoA/Rho kinase inhibitors (Y-27632 and RhoA siRNA) and LA-4 cells to antagonists of prostaglandin E2 (PGE2) receptor (EP4 [AH-23848]), PGD2 receptors (DP1 [BW A868C] and DP2 [BAY-u3405]), or the hepatocyte growth factor (HGF) receptor c-Met (PHA-665752), reversed EMT inhibition by the conditioned medium. Additionally, we found that apoptotic cell instillation inhibited bleomycin-mediated EMT in primary mouse alveolar type II epithelial cells in vivo. Our data suggest a new model for epithelial cell homeostasis, by which the anti-EMT programming of macrophages by apoptotic cells may control the progressive fibrotic reaction via the production of potent paracrine EMT inhibitors. PMID- 26875550 TI - [An updated review of 1p36 deletion (monosomy) syndrome]. AB - : The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. CONCLUSIONS: Approximately 100 cases have been documented since 1981. This rare disease is the most common subtelomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease. PMID- 26875551 TI - [Response to the Letter to the Editor: Diet, adolescence and pregnancy versus folic acid supplemation]. PMID- 26875552 TI - Slab fractures of the third tarsal bone: Minimally invasive repair using a single 3.5 mm cortex screw placed in lag fashion in 17 Thoroughbred racehorses. AB - REASONS FOR PERFORMING THE STUDY: A technique for minimally invasive repair of slab fractures of the third tarsal bone has not previously been reported. Results of third tarsal bone slab fracture repair in Thoroughbred racehorses are lacking. OBJECTIVES: To report the outcomes of repair of uniplanar frontal slab factures of the third tarsal bone using a single 3.5 mm cortex screw in lag fashion. STUDY DESIGN: Retrospective case series. METHODS: Case records of horses that had undergone this procedure were reviewed. RESULTS: Seventeen horses underwent surgery. Eighteen percent of cases had wedge shaped third tarsal bones. A point midway between the long and lateral digital extensor tendons and centrodistal and tarsometatarsal joints created a suitable entry site for implants. The fracture location, configuration and curvature of the third tarsal bone and associated joints requires a dorsolateral proximal-plantaromedial distal trajectory for the screw, which was determined by preplaced needles. There were no complications and fractures healed in all cases at 4-6 months post surgery. Seventy-nine percent of horses returned to racing and, at the time of reporting, 3 are in post operative rehabilitation programmes. CONCLUSION: The technique reported provides a safe, appropriate and repeatable means of repairing slab fractures of the third tarsal bone. Surgical repair is a viable alternative to conservative management. PMID- 26875554 TI - Increased use of antimicrobial medication in bulimia nervosa and binge-eating disorder prior to the eating disorder treatment. AB - OBJECTIVE: We examined the use of antimicrobial medication as a proxy for infections in large patient cohort treated for binge-eating disorder (BED), bulimia nervosa (BN), and anorexia nervosa (AN) over the five-year period preceding eating disorder treatment. METHOD: Patients (N = 1592) at the Eating Disorder Unit of Helsinki University Central Hospital between 2000 and 2010 were compared with matched general population controls (N = 6368). The study population was linked to the prescription data of antibacterial, antifungal and antiviral medication from the Register on Reimbursed Prescription Medicine. Data were analyzed using regression models. RESULTS: Individuals with BN and BED had received more often antimicrobial medication prescriptions compared to their controls (OR: 1.7, 95% CI: 1.3-2.1; OR: 2.6, 95% CI: 1.4-4.6, respectively), while no significant difference emerged in AN (OR: 0.9, 95% CI: 0.7-1.0, p = 0.10). Of the main drug categories, the respective pattern was seen in antibacterial and antifungal medication, while increased use for antivirals appeared only in BN (OR: 1.6, 95% CI: 1.1-2.3). Measured with the mean number of prescriptions or mean Defined Daily Doses per individual, patients with BN, BED and males with AN had also higher total antimicrobial medication use. DISCUSSION: Indicating increased infections, we found elevated use of antimicrobial medication in BN, BED and in males with AN. Infections may be consequence of hyperglycemia, weight gain, or dysregulation of intestinal microbiota associated with core eating disorder behaviors. Or the other way round; changes in intestinal microbiota due to infections, inflammation, or antibacterial medications might contribute to eating disorders in multiple ways. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:542-552). PMID- 26875553 TI - Direct interaction of the resistance to inhibitors of cholinesterase type 3 protein with the serotonin receptor type 3A intracellular domain. AB - Pentameric ligand-gated ion channels (pLGIC) are expressed in both excitable and non-excitable cells that are targeted by numerous clinically used drugs. Assembly from five identical or homologous subunits yields homo- or heteromeric pentamers, respectively. The protein known as Resistance to Inhibitors of Cholinesterase (RIC-3) was identified to interfere with assembly and functional maturation of pLGICs. We have shown previously for serotonin type 3A homopentamers (5-HT3A ) that the interaction with RIC-3 requires the intracellular domain (ICD) of this pLGIC. After expression in Xenopus laevis oocytes RIC-3 attenuated serotonin induced currents in 5-HT3A wild-type channels, but not in functional 5-HT3A glvM3M4 channels that have the 115-amino acid ICD replaced by a heptapeptide. In complementary experiments we have shown that engineering the Gloeobacter violaceus ligand-gated ion channel (GLIC) to contain the 5-HT3A -ICD confers sensitivity to RIC-3 in oocytes to otherwise insensitive GLIC. In this study, we identify endogenous RIC-3 protein expression in X. laevis oocytes. We purified RIC-3 to homogeneity after expression in Echericia coli. By using heterologously over-expressed and purified RIC-3 and the chimera consisting of the 5-HT3A -ICD and the extracellular and transmembrane domains of GLIC in pull-down experiments, we demonstrate a direct and specific interaction between the two proteins. This result further underlines that the domain within 5-HT3 A R that mediates the interaction with RIC-3 is the ICD. Importantly, this is the first experimental evidence that the interaction between 5-HT3 A R-ICD and RIC-3 does not require other proteins. In addition, we demonstrate that the pentameric assembly of the GLIC-5-HT3A -ICD chimera interacts with RIC-3. We hypothesized that pentameric ligand-gated ion channels (pLGICs) associate directly with the chaperone protein RIC-3 (resistance to inhibitors of cholinesterase type 3), and that the interaction does not require other protein factors. We found that the two proteins indeed interact directly, that the pLGIC intracellular domain is required for the effect, and that pLGICs in their pentameric form associate with RIC-3. These results provide the basis for future studies aimed at investigating which motifs provide the interaction surfaces, and at delineating the mechanism(s) of RIC-3 modulation of functional pLGIC surface expression. PMID- 26875555 TI - Characterizing MttA as a mitochondrial cis-aconitic acid transporter by metabolic engineering. AB - The mitochondrial carrier protein MttA is involved in the biosynthesis of itaconic acid in Aspergillus terreus. In this paper, the transport specificity of MttA is analyzed making use of different metabolically engineered Aspergillus niger strains. Furthermore, the mitochondrial localization of this protein is confirmed using fluorescence microscopy. It was found that MttA preferentially transports cis-aconitic acid over citric acid and does not transport itaconic acid. The expression of MttA in selected A. niger strains results in secretion of aconitic acid. MttA can be used in further strain engineering strategies to transport cis-aconitic acid to the cytosol to produce itaconic acid or related metabolites. The microbial production of aconitic acid (9g/L) is achieved in strains expressing this transport protein. Thus, metabolic engineering can be used for both the in vivo characterization of transport protein function like MttA and to make use of this protein by creating aconitic acid producing strains. PMID- 26875557 TI - A Heart too Drunk to Drive; AV Block following Acute Alcohol Intoxication. AB - Acute excessive alcohol consumption is associated with heart rhythm disorders like atrial fibrillation but also premature ventricular contractions, collectively known as the "holiday heart syndrome". More rarely but clinically significant are reports of atrioventricular (AV) conduction disturbances in binge drinkers with no underlying heart disease or chronic alcohol consumption. To obtain better insights into common denominators and the potential underlying mechanisms we collected and compared individual case reports of AV block following acute alcohol intoxication in otherwise healthy people. By screening PubMed, Google Scholar, Scopus and JSTOR, fifteen cases were found of which eight were sufficiently documented for full analysis. Blood alcohol levels ranged from 90 to 958 mg/dl (19 to 205 mM). Second and third degree AV block was observed most (6/8) albeit that in two of these patients a vagal stimulus led to deterioration from first into higher order AV block. In all cases, patients reverted to normal sinus rhythm upon becoming sober again. Mildly lowered body temperature (35.9 +/- 0.5 degrees C) was observed but can be excluded as a major cause of conduction blockade. We hypothesize that ethanol induced partial inhibition of calcium and potentially also sodium currents in conductive tissue structures may be one of the mechanisms of conduction slowing and block that may become exaggerated upon increased vagal tone. An impairment of gap junction function cannot be excluded as a contributing factor. In conclusion, cases of documented alcohol induced AV block are very rare but events can occur at relatively low serum alcohol levels which should prompt to awareness of this phenomenon in alcohol intoxicated patients. PMID- 26875556 TI - Follicular thyroid carcinoma but not adenoma recruits tumor-associated macrophages by releasing CCL15. AB - BACKGROUND: The differential diagnosis of follicular thyroid carcinoma (FTC) and follicular adenoma (FA) before surgery is a clinical challenge. Many efforts have been made but most focusing on tumor cells, while the roles of tumor associated macrophages (TAMs) remained unclear in FTC. Here we analyzed the differences between TAMs in FTC and those in FA. METHODS: We first analyzed the density of TAMs by CD68 immunostaining in 59 histologically confirmed FTCs and 47 FAs. Cytokines produced by FTC and FA were profiled using antibody array, and validated by quantitative PCR. Chemotaxis of monocyte THP-1 was induced by condition medium of FTC cell lines (FTC133 and WRO82-1) with and without anti CCL15 neutralizing antibody. Finally, we analyzed CCL15 protein level in FTC and FA by immunohistochemistry. RESULTS: The average density of CD68(+) cells was 9.5 +/- 5.4/field in FTC, significantly higher than that in FA (4.9 +/- 3.4/field, p < 0.001). Subsequently profiling showed that CCL15 was the most abundant chemokine in FTC compared with FA. CCL15 mRNA in FTC was 51.4-folds of that in FA. CM of FTC cell lines induced THP-1 cell chemotaxis by 33 ~ 77%, and anti CCL15 neutralizing antibody reduced THP-1 cell migration in a dose-dependent manner. Moreover, we observed positive CCL15 immunostaining in 67.8% of FTCs compared with 23.4% of FAs. CONCLUSION: Our study suggested FTC might induce TAMs infiltration by producing CCL15. Measurement of TAMs and CCL15 in follicular thyroid lesions may be applied clinically to differentiate FTC from FA pre operation. PMID- 26875558 TI - Inhibition of Neuropathic Pain by a Single Intraperitoneal Injection of Diazepam in the Rat: Possible Role of Neurosteroids. AB - Diazepam binds with the same high affinity to the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor, which has been renamed translocator protein (TSPO). Both receptors could promote neurosteroid synthesis. In the present study, we investigated whether a single dose of diazepam could inhibit neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), and whether CBR and TSPO mediated this effect. We found that a single intraperitoneal injection of diazepam 9 d after L5 SNL significantly depressed the established mechanical allodynia and thermal hyperalgesia, which persisted until the end of the experiments. Furthermore, the effects were mimicked by a single intraperitoneal injection of Ro5-4864, a specific TSPO agonist and pregnenolone, a neurosteroid precursor. In addition, we found that the inhibitory effect of diazepam was also completely blocked by pretreatment with a specific CBR antagonist, flumazenil. The effects of diazepam or Ro5-4864 on neuropathic pain were completely blocked by pretreatment with a neurosteroid synthesis inhibitor, aminoglutethimide (AMG). Finally, any one of the three drugs, diazepam, Ro5-4864 and pregnenolone, could reduce the activation of astrocytes and the production of interleukin-1beta (IL-1beta) in the L5 spinal dorsal horn 14 d after L5 SNL. These results suggest that in addition to exerting effects on CBR, diazepam may inhibit neuropathic pain via TSPO, which promotes neurosteroid formation, subsequently reducing the activation of astrocytes and production of cytokines. PMID- 26875559 TI - Involvement of TRPV1 in the Olfactory Bulb in Rimonabant-Induced Olfactory Discrimination Deficit. AB - Rimonabant is well recognized as a cannabinoid CB1 receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB1 receptors, it also exerts several pharmacological and behavioral effects independent of CB1 receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1). Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution. Interestingly, CB1 receptor has recently been suggested to play a role in olfactory functions. Olfaction not only is involved in food intake, visual perception and social interaction, but also is proposed as a putative marker for schizophrenia and autism. Therefore, the present study aimed to investigate whether CB1 receptor and TRPV1 played a role in olfactory functions. We first used the genetic disruption approach to examine the role of CB1 receptor in olfactory functions and found that CB1 knockout mice exhibited olfactory discrimination deficit. However, it is important to point out that these CB1 knockout mice, despite their normal locomotivity, displayed deficiencies in the olfactory foraging and novel object exploration tasks. These results imply that general exploratory behaviors toward odorant and odorless objects are compromised in CB1 knockout mice. We next turned to the pharmacological approach to examine the role of CB1 receptor and TRPV1 in olfactory functions. We found that the short-term administration of rimonabant, injected systemically or directly into the olfactory bulb (OB), impaired olfactory discrimination that was rescued by the TRPV1 antagonist capsazepine (CPZ), via the same route of rimonabant, in wild-type mice. These results suggest that TRPV1 in the OB is involved in rimonabant-induced olfactory discrimination deficit. However, the rimonabant and/or CPZ treatments neither affected locomotivity nor general exploratory behaviors in wild-type mice. Finally, the acute systemic administration of rimonabant, unlike the short-term administration regimen, did not affect olfactory discrimination. Taken together, this study not only is the first one, to the best of our knowledge, suggests that the olfactory TRPV1 plays a role in olfactory functions, but also provides a possible mechanism for the olfactory discrimination deficit induced by rimonabant. PMID- 26875560 TI - Environmental Factors Responsible for Variability of Hepatic Vein Flow: A Doppler Assessment in Healthy Twins. AB - Doppler interrogation studies of the liver blood flow indicate altered hepatic vein waveforms in association with impaired hepatocellular function. However, little is known about the mechanisms responsible for variations of these parameters in the absence of disease. We aimed to investigate the contribution of heritable and environmental factors to the physiological variability of hepatic vein flow in a twin cohort. Two hundred twenty-eight healthy adult Hungarian twins (69 monozygotic, 45 same-sex dizygotic pairs) underwent Doppler sonography of the hepatic vein. Age- and sex-adjusted heritability of the highest velocity (amplitude of S wave) of hepatic vein flow was negligible. Shared environment contributed to 33% (95% CI, 16%-51%), and unshared environment was responsible for the largest portion (67%; 95% CI, 49%-84%) of the variance. Duration of sports activities was significantly (P < 0.05) related to the magnitude of hepatic vein flow, while other risk factors and lifestyle characteristics had no significant influence. The data suggest that genetic factors have little impact on the parameters of hepatic venous blood flow. The variability observed in healthy twins by the Doppler interrogation can be explained by the effect of unshared environmental components primarily related to regular physical activity. These findings underscore the importance of unique environments in physiological variations of hepatic venous blood flow. PMID- 26875561 TI - Activation of Strychnine-Sensitive Glycine Receptors by Shilajit on Preoptic Hypothalamic Neurons of Juvenile Mice. AB - Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 MUM tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 MUM strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with alpha2/alpha2beta subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically. PMID- 26875562 TI - Inhibitory Effects of Hydrogen on Proliferation and Migration of Vascular Smooth Muscle Cells via Down-Regulation of Mitogen/Activated Protein Kinase and Ezrin Radixin-Moesin Signaling Pathways. AB - Molecular hydrogen (H2) has recently attracted considerable attention for the prevention of oxidative stress-related vascular diseases. The purpose of this study is to evaluate the effects of hydrogen on proliferation and migration of vascular smooth muscle cells (VSMCs) stimulated by angiotensin II (Ang II) in vitro, and on vascular hypertrophy induced by abdominal aortic coarctation (AAC) in vivo. Hydrogen-rich medium (0.6~0.9 ppm) was added 30 min before 10-7 M Ang II administration, then the proliferation and migration index were determined 24 h after Ang II stimulation. Hydrogen gas (99.999%) was given by intraperitoneal injection at the dose of 1 ml/100 g/day consecutively for one week before AAC and lasted for 6 weeks in vivo. Hydrogen inhibited proliferation and migration of VSMCs with Ang II stimulation in vitro, and improved the vascular hypertrophy induced by AAC in vivo. Treatment with hydrogen reduced Ang II- or AAC-induced oxidative stress, which was reflected by diminishing the induction of reactive oxygen species (ROS) in Ang II-stimulated VSMCs, inhibiting the levels of 3 nitrotyrosine (3-NT) in vascular and serum malondialdehyde (MDA). Hydrogen treatment also blocked Ang II-induced phosphorylation of the extracellular signal regulated kinase1/2 (ERK1/2), p38 MAPK, c-Jun NH2-terminal kinase (JNK) and the ezrin/radixin/moesin (ERM) in vitro. Taken together, our studies indicate that hydrogen prevents AAC-induced vascular hypertrophy in vivo, and inhibits Ang II induced proliferation and migration of VSMCs in vitro possibly by targeting ROS dependent ERK1/2, p38 MAPK, JNK and ERM signaling. It provides the molecular basis of hydrogen on inhibiting the abnormal proliferation and migration of VSMCs and improving vascular remodeling diseases. PMID- 26875563 TI - Effects of Sodium Benzoate Treatment in Combination with An Extinction Training on the Maintenance of Cocaine-Supported Memory. AB - Activation of N-methyl-D-aspartate (NMDA) receptor can facilitate the extinction of various maladaptive memories. Sodium benzoate (NaB) has been known to enhance a naturally occurring full agonist on the glycine binding site of the NMDA receptor. This study aimed to test whether systemic NaB treatment can affect the extinction of a cocaine-supported memory, the cocaine-induced conditioned place preference (CPP). Following the establishment of the cocaine (10 mg/kg/conditioning * 3)-induced CPP, an extinction protocol, consisting of two consecutive extinction training bouts at an 8-h interval, was used. NaB (500 mg/kg) or an equivalent volume of saline was given immediately following each extinction training bout to test the modulating effect of NaB on the maintenance of cocaine-induced CPP. Moreover, NaB was bilaterally micro-infused into the medial prefrontal cortex (mPFC) to validate the involvement of this brain region in mediating systemic NaB treatment-produced effect on cocaine-induced CPP. Systemic (500 mg/kg) and intra-mPFC (10 MUg/side) NaB treatment significantly decreased subsequent cocaine-induced CPP magnitude, although the NaB treatment or the extinction training alone did not affect such CPP magnitude. It was of importance to note that systemic or intra-mPFC NaB delivery did not affect mouse locomotor activity in the retests. These results, taken together, suggest that NaB treatment in combination with the extinction training may facilitate the extinction of the cocaine-supported memory. Moreover, systemic NaB treatment exerts such effects, at least in part, via its effect in the mPFC. PMID- 26875564 TI - Altered expression of human endogenous retroviruses syncytin-1, syncytin-2 and their receptors in human normal and gestational diabetic placenta. AB - INTRODUCTION: Syncytins belong to the Human Endogenous Retrovirus family. The syncytin-1 receptor, SLC1A5, and syncytin-2 receptor, MFSD2, interact with their respective syncytin proteins to induce syncytiotrophoblast formation. However, there is no information about syncytins in gestational diabetic placenta. Therefore, we studied the expression and localization of syncytins and their receptors during normal placental development and in gestational diabetic placenta. METHODS: Immunohistochemistry and Western-blot methods were performed with antibodies against syncytin-1, syncytin-2, SLC1A5 and MFSD2 in human first trimester placental tissues, normal term and gestational diabetic placentas. Syncytin-1, syncytin-2 and MFSD2 mRNA transcripts were determined by qRT-PCR in normal and diabetic term placentas. RESULTS: Cytoplasmic syncytin-1, syncytin-2, SLC1A5 and MFSD2 immunoreactions were observed in the trophoblastic layers in all placental samples. Some of the stromal cells showed strong cytoplasmic punctate staining. There were significantly weak syncytin-2 and MFSD2 immunoreaction intensities in diabetic placentas by ImageJ analysis, in parallel with decreased syncytin-2 and MFSD2 proteins in diabetic placentas by Western-blot. Protein expression of SLC1A5 increased dramatically in early pregnancy compared to term placenta. Syncytin-1, syncytin-2 and MFSD2 mRNA transcripts showed similar relative expression pattern by qRT-PCR. DISCUSSION: Syncytins were localized not only in cytotrophoblast cells and the basement membrane of the syncytiotrophoblast but also in the apical microvillous membrane and cytoplasm of syncytiotrophoblast, and some of the stromal cells and endothelium. Decreased syncytin-2 and MFSD2 proteins in gestational diabetic placentas might cause abnormal syncytiotrophoblast formation and possibly be involved in the pathology. Therefore, our study highlights an important potential relationship between syncytins and gestational diabetic placenta. PMID- 26875565 TI - The Cognitive Psychopathology of Internet Gaming Disorder in Adolescence. AB - Adolescents are known to be an at-risk population for developing Internet gaming disorder (IGD). A recent clinical model has proposed that adolescents with IGD may endorse a unique set of maladaptive beliefs that underlie persistent and excessive involvement in Internet gaming activities. These include (a) beliefs about game reward value and tangibility, (b) maladaptive and inflexible rules about gaming behaviour, (c) over-reliance on gaming to meet self-esteem needs, and (d) gaming as a method of gaining social acceptance. A sample of 824 adolescents (402 male and 422 female) were recruited from multiple secondary schools and administered a survey that included measures of IGD symptomatology, problematic Internet gaming cognition, and psychological distress. The results showed that adolescents with IGD report significantly more maladaptive gaming beliefs than adolescents without IGD, including those who play Internet games for more than 30 h per week. The size of observed effects were large. The strong association between gaming cognitions and IGD symptoms still held after controlling for measures of gaming activity and psychological distress. These findings indicate that adolescents with IGD have distinct problematic thoughts about gaming, and highlight the importance of addressing these cognitions in therapeutic interventions for the disorder. PMID- 26875566 TI - Cohort Profile: A study of influenza immunity in the urban and rural Guangzhou region of China: the Fluscape Study. PMID- 26875567 TI - [Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method]. AB - OBJECTIVE: Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. METHODS: After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. RESULTS: The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. CONCLUSIONS: There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice. PMID- 26875568 TI - N, N-Dimethylglycine decreases oxidative stress and improves in vitro development of bovine embryos. AB - The antioxidant effect of N, N-dimethylglycine (DMG) on in vitro-produced (IVP) bovine embryos was examined. After in vitro fertilization, presumptive zygotes were cultured with or without 0.1 MUM DMG under different oxygen tensions. The percentage of embryos developing to the blastocyst stage was lowest under a 20% oxygen concentration without DMG, and it was significantly increased (P < 0.05) by applying a 5% oxygen concentration. Under the 20% oxygen concentration, supplementation of the medium with DMG significantly improved blastocyst development, which was nearly equal to that achieved under 5% oxygen without DMG. Furthermore, a tendentious increase (P = 0.06) in blastocyst cell numbers was observed when DMG was applied. In the second experiment, addition of H2O2 (0.5 mM) to the culture medium significantly (P < 0.01) reduced the percentage of embryos developing to the blastocyst stage. However, DMG supplementation prevented this reduction. In conclusion, DMG enhanced the invitro development of IVP bovine embryos by acting as an antioxidant. PMID- 26875569 TI - The case for targeting community pharmacy-led health improvement: Findings from a skin cancer campaign in Wales. AB - The use of community pharmacies to deliver health improvement campaigns is well established. Cancer incidence is closely related to increasing levels of deprivation. Because community pharmacies are more prevalent in deprived areas there is potential for them to make an important contribution to health improvement by delivering interventions aimed at reducing cancer incidence amongst those at greatest risk. OBJECTIVES: The aims of the study were: to examine the association between high risk behaviour and deprivation and contribute evidence to the case for or against targeting cancer prevention campaigns at specific risky behaviour in areas of high deprivation. METHODS: This study has an ecological design and involved retrospective analysis of data derived from 5739 sun-safety quizzes completed by pharmacy users at 714 community pharmacies in Wales during May 2014. RESULTS: Levels of participation in the campaign and high risk sun-safety behaviours were higher in more deprived areas. Respondents from deprived areas had significantly lower sun-safety knowledge. 3802 (66.2%) respondents reported 'excellent' or 'good' knowledge of behaviours which promote sun-safety but this did not necessarily translate into how individuals behaved. 3787 (66.1%) respondents considered community pharmacies an acceptable location for the campaign and for discussing the signs and symptoms of skin cancer. KEY FINDINGS: Results show association between high risk behaviour and geographically defined deprivation adding to the case for targeting cancer prevention campaigns at specific behaviours and geographies. CONCLUSIONS: Community pharmacies appear to be acceptable locations from which to deliver health improvement campaigns in terms of participant recruitment, ease of delivery, and pharmacy user feedback. PMID- 26875571 TI - [An international standard of clinical practice with Chinese characteristics]. PMID- 26875570 TI - Finding common task-related regions in fMRI data from multiple subjects by periodogram clustering and clustering ensemble. AB - We propose an innovative and practically relevant clustering method to find common task-related brain regions among different subjects who respond to the same set of stimuli. Using functional magnetic resonance imaging (fMRI) time series data, we first cluster the voxels within each subject on a voxel by voxel basis. To extract signals out of noisy data, we estimate a new periodogram at each voxel using multi-tapering and low-rank spline smoothing and then use the periodogram as the main feature for clustering. We apply a divisive hierarchical clustering algorithm to the estimated periodograms within a single subject and identify the task-related region as the cluster of voxels that have periodograms with a peak frequency matching that of the stimulus sequence. Finally, we apply a machine learning technique called clustering ensemble to find common task-related regions across different subjects. The efficacy of the proposed approach is illustrated via a simulation study and a real fMRI data set. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26875572 TI - [The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision) : interpretation of diagnosis]. PMID- 26875573 TI - [The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision) : interpretation of initial treatment]. PMID- 26875574 TI - [The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision) : interpretation of the treatment of relapsing and refractory multiple myeloma]. PMID- 26875575 TI - [The guidelines for the diagnosis and management of multiple myeloma in China (2015 revision) : interpretation of response criteria]. PMID- 26875576 TI - [A comparison of efficacy and safety of linezolid versus vancomycin for the treatment of infections in patients after allogeneic hematopoietic stem cell transplantation]. AB - OBJECTIVE: To compare the efficacy and safety of linezolid and vancomycin in patients diagnosed as gram positive bacterial infections after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 131 patients who were confirmed or suspected as gram positive coccal infections after allo-HSCT were enrolled in our study from July 2010 to December 2012. Patients were administrated with linezolid (600 mg every 12 h) or vancomycin (1 g every 12 h). Clinical efficacy and safety were compared between the two groups. RESULTS: A total of 136 cases were detected gram positive coccal infections, among whom 120 cases were evaluable. Finally, 37 cases receiving linezolid and 83 cases receiving vancomycin were enrolled in this study. Clinical cure rates of infections were 81.1% (30/37) and 88.0% (73/83) in linezolid and vancomycin groups, respectively(P=0.319). The incidence of adverse reactions was similar in the two groups[50.0% (23/40) vs 45.6% (41/90), P=0.623]. Drug-related renal function injury was mild [6.5% (3/46) vs 6.7% (6/90), P=1.000]. The occurrence of liver damage with moderate and severe elevation enzymes was also similar between the two groups [2.2% (1/46) vs 6.7% (6/90), P=0.244]. As for hematologic events, linezolid was not found to have a negative effect on hematopoietic reconstitution. CONCLUSIONS: Linezolid is as effective as vancomycin in the treatment of gram positive bacterial infections after allo HSCT. Safety of Linezolid is also comparable with that of vancomycin, which needs to be further studied due to the complex interaction of medication in this special population. PMID- 26875578 TI - [Cytomegalovirus infection after haploidentical stem cell transplantation may reduce relapse risk in leukemia]. AB - OBJECTIVE: To analyze the relationship between cytomegalovirus (CMV) reactivation and leukemia relapse after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: A total of 61 patients diagnosed as hematological malignancies undergoing haplo-HSCT were analyzed retrospectively in our center. RESULTS: In the cohort, 36 patients had CMV reactivation after haplo-HSCT. The 100-day cumulative incidence of CMV reactivation was 59%. Compared with that in patients without CMV reactivation after transplantation, the incidence of leukemia relapse was lower in patients with CMV reactivation (16.9% vs 40.0%, P=0.034). The correlation of CMV reactivation and decreased relapse rate was only found in patients with acute myeloid leukemia (P=0.019). In multivariate analysis, relapsed disease status before transplant was a significant negative predictor of overall survival (OS) and relapse after transplant (RR was 2.866 and 3.331 respectively). CMV reactivation after transplant had a protective effect on disease relapse (RR=0.300, P=0.047). CONCLUSIONS: The rate of CMV reactivation after haplo-HSCT is high. CMV reactivation may reduce risk of relapse in patients diagnosed as acute myeloid leukemia undergoing haplo-HSCT. However, CMV reactivation is one of the important predictors of non-relapse death after transplant, active anti-viral treatment is still needed. PMID- 26875577 TI - [A clinical study of acute lymphoblastic leukemia in adolescents: a single center experience]. AB - OBJECTIVE: To explore the clinical and laboratory characteristics, treatment, prognostic factors of acute lymphoblastic leukemia (ALL) in adolescents. METHODS: Adolescents de novo ALL patients in Blood Disease Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences from September 1999 to September 2013 were enrolled in this study. Clinical data, therapeutic effect and prognostic factors were retrospectively analyzed. RESULTS: Of all 94 patients, 91 patients were treated in our center. The overall complete remission (CR) rate was 96.7% (88/91), CR rate after one cycle was 91.2%(83/91). The median follow-up time was 18 months. In all patients, the 6-year anticipated overall survival (OS) rate and disease free survival (DFS) rate were (47.6 +/- 6.7)% and (45.4 +/- 6.0)% respectively. In standard risk ALL patients , 6-year anticipated OS rate and DFS rate were (65.7 +/- 8.1)% and (65.3 +/- 7.4)%. Hyperleukocytosis (white blood cell count >=30 * 10(9)/L in B-ALL; >=100 * 10(9)/L in T-ALL), Ph(+) , MLL(+) , hypodiploid were risk factors associated with poor clinical outcome. CONCLUSIONS: The therapeutic effect and clinical outcome in adolescents with ALL are relatively favorable, especially in standard risk group. In high risk ALL patients, allogeneic hematopoietic stem cell transplantation may improve therapeutic efficacy. PMID- 26875579 TI - [A study of immunocyte subsets and serum cytokine profiles before and after immunal suppression treatment in patients with immune thrombocytopenia]. AB - OBJECTIVE: To explore the clinical significance of a series of cytokines and peripheral blood immunocyte subsets before and after immunosuppressive therapy in patients with immune thrombocytopenia (ITP). METHODS: The percentages of immunocyte subsets in the peripheral blood of 20 patients with ITP and 20 healthy controls were detected by flow cytometry, including CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), CD19(+). ELISA was applied to detect the level of serum TNFalpha, IL-2, IL-6, IL-4, IL-10, IL-11, IL-17, IL-27, transforming growth factor beta (TGFbeta), thrombopoietin (TPO) of 20 patients with ITP and 20 healthy controls. RESULTS: The percentage of CD3(+) T lymphocyte, CD4(+) T lymphocyte and the ratio of CD4(+)/CD8(+) T lymphocyte in patients with ITP were lower than those in healthy controls[(62.66 +/- 6.58)% vs (69.93 +/- 4.81)%, (29.46 +/- 5.02)% vs (39.08 +/- 3.50)%, 0.97 +/- 0.35 vs 1.56 +/- 0.26, all P<0.05]. After immunosuppressive therapy, the percentage of CD3(+) T lymphocyte, CD4(+) T lymphocyte and the ratio of CD4(+)/CD8(+) T lymphocyte [(71.49 +/- 5.16)%, (39.25 +/- 3.21)% and 1.56 +/- 0.28] recovered to the same levels in healthy controls. The percentage of CD8(+) T lymphocyte and CD19(+) B lymphocyte in patients with ITP were higher than those in the healthy controls [(30.28 +/- 4.63)% vs (25.90 +/- 3.06)%, (18.92 +/- 4.27)% vs (13.17 +/- 3.64)%, all P<0.05]. After treatment of immunosuppressive therapy, the percentage of CD8(+) T lymphocyte and CD19(+) B lymphocyte [(25.16 +/- 3.45)% and (11.98 +/- 3.68)%] recovered to the similar levels in healthy controls. The serum levels of IL-4, IL-6, IL-11, IL-17 and TPO in patients with ITP were significantly higher than those in healthy controls. While TGFbeta level was significantly decreased. There was no significant difference of IL-27 between ITP patients and healthy controls. After the treatment of immunosuppressive therapy, IL-4, IL-6, IL-11, IL-17, TPO and TGFbeta were down-regulated while IL-27 was up-regulated. There was no significant difference of IFNgamma, TNFalpha, IL-2 and IL-10 among ITP patients before or after immunosuppressive therapy and healthy controls. CONCLUSIONS: The present study suggests that the aberrant immunocyte subsets and cytokines are involved in the pathogenesis of ITP. Hyper-function of Th2 and Th17, dysfunction of Treg cells, up-regulation of IL-27, IL-11, TPO and other factors may contribute to the pathogenesis of ITP. PMID- 26875580 TI - [Clinical characteristics of 35 non-pregnant patients with Listeria monocytogenes sepsis]. AB - OBJECTIVE: To better understand the clinical characteristics and predisposing factors in non-pregnant patients with Listeria monocytogenes (Listeria) sepsis. METHODS: Clinical data were collected at Peking Union Medical College Hospital between January 2002 and December 2014. A case with non-pregnant Listeria sepsis is defined as a non-pregnant person with clinically compatible illness and from whom Listeria was isolated from his/her blood culture. We define an underlying condition if a patient has been diagnosed of and/or has been treated for a concurrent baseline disease within 1 month prior to the onset of Listeria sepsis. RESULTS: A total of 35 patients were enrolled. The age of all patients was (49.1 +/- 17.0) years. The male to female ratio was 2: 3. Most patients were combined with at least 1 underlying condition (33, 94.3%), including 42.9% patients with an autoimmune disease, 34.3% with malignancies. The majority (91.4%) represented an acute onset (<1 week) with median time of 3 days. Clinical manifestations included fever (34/35, 97.1%), central nervous system (CNS) symptoms (17/35, 48.6%), gastrointestinal tract symptoms (13/35, 37.1%). Fourteen patients had undergone lumber puncture and cerebral spinal fluid (CSF) tests, which revealed abnormalities comparable of Listeria meningitis. Listeria was isolated from CSF in 11 of 14 patients (78.6%). There were 34 patients receiving empiric antibiotics including 54.3% cephalosporins which are resistant to Listeria. Twenty five (71.4%) patients were switched to the target antimicrobials according to positive blood culture. Of the 35 patients with Listeria sepsis, 21 (60.0%) recovered or were cured, however the rest (40.0%) had dismal outcome. Six patients died in hospital, 8 critical patients were discharged and died after transferring to local hospitals. CONCLUSIONS: Listeria sepsis is commonly associated with non-pregnant patients with compromised immune function. Clinical presentations include acute fever, CNS symptoms and gastrointestinal symptoms etc. Empiric antibiotics covering Listeria should be considered when sepsis is suspected among susceptible hosts. PMID- 26875581 TI - [Analysis of clinical manifestations and risk factors of mortality in Acinetobacter baumannii bloodstream infection]. AB - OBJECTIVE: To explore the clinical manifestations, antimicrobial therapy, and risk factors of mortality in patients with Acinetobacter baumannii bloodstream infection. METHODS: Clinical data of 153 patients with Acinetobacter baumannii bloodstream infection hospitalized in First Affiliated Hospital of Zhejiang University from January 2013 to September 2014 were analyzed retrospectively.According to the 28-day survival after diagnosis, the patients were divided into death group (n=76) and survival group (n=77). Data related to demographic and clinical characteristics, underlying diseases, treatment, invasive procedures, bacterial resistance to antibiotics, acute physiology and chronic health evaluation II(APACHEII )scores at onset, and antimicrobial therapy were collected.The index as an independent risk factor of mortality was demonstrated by multivariate logistic regression analysis. RESULTS: This study included 153 patients with Acinetobacter baumannii bloodstream infection. The 28 day mortality was 49.7%. The independent risk factors of mortality were APACHE II score >= 22 at onset (OR=15.7, 95%CI 5.1-48.1, P<0.001), septic shock(OR=6.3, 95%CI 1.9-21.3, P=0.003), and administration of steroids(OR=3.6, 95%CI 1.0-12.3, P=0.043). Compared with subjects treated with non-cefoperazone-sulbactam-based regimen , those treated with cefoperazone-sulbactam for multidrug-resistant Acinetobacter baumannii(MDR-AB) had significantly lower mortality on day7, day14 and day28(8.9% vs 59.2%, 31.1% vs 65.8%, 44.4% vs 72.4% respectively). CONCLUSIONS: The patients with Acinetobacter baumannii bloodstream infection have high mortality within one month. Administration of steroids and septic shock are associated with poor prognosis. APACHEII score >= 22 at onset predicts adverse outcome. Cefoperazone-sulbactam-based antimicrobial therapy improves patients' survival. PMID- 26875582 TI - [The clinical characteristics and prognosis of patients with peripartum cardiomyopathy]. AB - OBJECTIVE: To explore the clinical characteristics and risk factors in patients with peripartum cardiomyopathy (PPCM). METHODS: A total of 35 patients admitted in Peking Union Medical College Hospital and diagnosed with PPCM between January 1995 and December 2014 was included and analyzed in this study. The subjects were divided into two groups: the early recovery and delayed recovery. Early recovery was defined as normalization of left ventricle ejection fraction (LVEF) >=50% before 6 months post-diagnosis. Delayed recovery was defined if the length of time required for recovery of LVEF was longer than 6 months or death was reported during follow-up. Risk factors for delayed recovery were assessed. RESULTS: The incidence of PPCM was 1 per 1 067 deliveries between the study periods. The age of the 35 patients was (28.9 +/- 5.6) years old. Among them, 20 (57.1%) patients were not in the first pregnancy, 13 (37.1%) had delivered before, and 5 (14.3%) patients had twin pregnancies. The LVEF at diagnosis was (34.1 +/- 8.0) %. 62.9% (22 cases) of the subjects were in the early recovery, while 37.1% (13 cases) of the subjects were in the delayed recovery group, 2 of whom suffered death. Multivariate logistic regression indicated that LVEF(OR=1.339, 95%CI 1.063-1.688, P=0.013)and left ventricle end-dilated diameter(OR 0.763, 95%CI 0.607-0.960, P=0.021)were independent risk factors for delayed recovery. CONCLUSIONS: PPCM is a rare but life-threatening complication of pregnancy. LVEF and left ventricle end-dilated diameter at diagnosis were two independent factors associated with the prognosis of PPCM. PMID- 26875583 TI - [A comparison study of diagnostic value between the old and revised guidelines in patients with idiopathic pulmonary fibrosis]. AB - OBJECTIVE: To compare the strengths and limitations of the old and revised guidelines for the diagnosis in patients with idiopathic pulmonary fibrosis(IPF). METHODS: Patients who were admitted and diagnosed as interstitial lung diseases (ILDs) in our hospital from 2009 to 2014 were enrolled in our study.Eachpatient was reevaluated respectively according to the old and revised guidelines of IPF. RESULTS: A total of 553 cases were initially reviewed, among whom 355 cases were excluded for pulmonary fibrosis secondary to definite underlying diseases, 28 excluded due to high resolution computed tomography(HRCT) not done, 26 excluded because serum immunology examination was not available.The remaining 144 cases were finally enrolled in this study including 92 males and 52 females with median age 21-92 (68 +/- 11) years old. Twenty five patients (17.4%, 25/144) met the diagnostic criteria of IPF by the old guideline.While by the revised guideline, 53 patients (36.8%, 53/144) were diagnosed as classical IPF, 29 patients(20.1%, 29/144) as probable cases, another 69 non-IPF patients accounting for 43.1% (62/144). The result revealed that there's a significant difference between the two guidelines in the diagnosis of IPF. CONCLUSIONS: The revised guideline favors an early diagnosis of IPF and simplifies the diagnostic process.However the possibility of over diagnosis or missed diagnosis by the revised guideline does exist.On the other hand, despite of the delayed diagnosis by the old guideline, it may reduce the misdiagnosis of IPF in some circumstance. PMID- 26875584 TI - How Can the Complications of Central Vein Catheters Be Reduced?: Intraluminal Prophylaxis and Management of Catheter Infections: Role of Antibiotic Locks. PMID- 26875585 TI - The overlap of upper functional gastrointestinal disorders with irritable bowel syndrome in Chinese outpatients: A multicenter study. AB - BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a common functional bowel disease, and the overlap with upper functional gastrointestinal disorders (FGIDs) is popular. However, the coexistent upper GI symptom profiles, upper FGID spectra, and related risk factors among IBS subjects remain unclear in mainland of China. METHODS: Consecutive patients from the outpatient gastroenterology clinics of three tertiary hospitals in China were enrolled in this multicenter study. All upper GI symptoms occurring at least once a week in the last 3 months were recorded. Diagnostic criteria of functional esophageal, gastroduodenal disorders and IBS were based on Rome III criteria. Risk factors were assessed using a multivariate logistic regression model. RESULTS: Of the 8906 consecutive patients, 751 patients met Rome III criteria for IBS and 735 IBS patients participated in the interview. Postprandial fullness (30.6%), belching (27.1%), and regurgitation (21.8%) were the three most prevalent upper GI symptoms in IBS. Functional dyspepsia (FD, 36.7%), belching disorders (27.1%), and functional heartburn (16.3%) were the three most frequent upper FGID in IBS patients. Female sex, divorced or widowed versus married status, defecation straining, reduced bowel movement, mixed IBS, abdominal distention, mild abdominal pain, moderate discomfort were positively associated with IBS-FD overlap. Female sex, drinking, moderate discomfort, and mild to moderate distension were independent risk factors for IBS-belching disorder overlap. CONCLUSIONS: The study provides detailed overlap spectra of upper FGID with IBS. Mixed IBS is an important risk factor for IBS-FD overlap, which deserved more concern. PMID- 26875586 TI - Self-weighing and simple dietary advice for overweight and obese pregnant women to reduce obstetric complications without impact on quality of life: a randomised controlled trial. AB - OBJECTIVE: To determine the effect of serial weighing and dietary advice compared with standard antenatal care on obstetric outcomes. DESIGN: Randomised controlled clinical trial. SETTING: Australian tertiary obstetric hospital. POPULATION: Three hundred and eighty-two overweight or obese non-diabetic pregnant women at less than 20 weeks gestation with a singleton pregnancy. METHODS: Women were randomised to targeted, serial self-weighing and simple dietary advice, (intervention), or standard antenatal care (control). MAIN OUTCOMES MEASURES: The primary outcome was a reduction in a composite of obstetric complications: gestational hypertension, pre-eclampsia, diabetes, assisted or caesarean birth, shoulder dystocia, severe perineal trauma, postpartum haemorrhage and maternal high dependency care. Secondary outcomes were gestational weight gain at 36 weeks' gestation, quality of life (QOL) and maternal serum levels of 28-week leptin, adiponectin and C-reactive protein (CRP). RESULTS: There was no difference in the rate of the primary composite outcome of obstetric complications: 124/184 (67% control), 124/187 (66% intervention) [relative risk 0.98 (95% confidence interval (CI) 0.85-1.14)]. There was no difference in mean gestational weight gain [-0.9 kg (95% CI -2.0, 0.25)], QOL or leptin, adiponectin or CRP levels between intervention and control groups. CONCLUSIONS: This low cost, pragmatic intervention failed to prevent obstetric complications or modify maternal biochemistry or gestational weight gain in overweight or obese pregnant women. Participation in the study did not impair participants' QOL. TWEETABLE ABSTRACT: Serial self-weighing and dietary advice failed to reduce obstetric complications in overweight pregnant women. PMID- 26875587 TI - Angiosarcoma of the thoracic wall responded well to nanoparticle albumin-bound paclitaxel: A case report. AB - An 81-year-old woman visited a local clinic due to chest pain and a skin induration on the right precordia. She had a history of right breast cancer, and she had undergone a mastectomy and radiation therapy 10 years prior. Computed tomography (CT) imaging of the chest demonstrated a lobular mass that involved the right anterior thoracic wall and partially extruded from the thoracic cavity into the subcutaneous tissue. The tumor was surgically excised, and pathological analyses yielded a diagnosis of angiosarcoma. Five months after the operation, CT imaging showed multiple masses on the right pleura, indicating a local relapse and pleural dissemination of the angiosarcoma. Systemic chemotherapy composed of nanoparticle albumin-bound paclitaxel (nab-PTX) (80 mg/m(2)) was delivered weekly. After 4 courses of chemotherapy, the tumors regressed remarkably. Nab-PTX may be an effective treatment option for recurrent or metastatic angiosarcoma. PMID- 26875589 TI - Glycemic control and complications in patients with type 1 diabetes - a registry based longitudinal study of adolescents and young adults. AB - OBJECTIVE: The main aims of this study were to assess longitudinal glycemic control and the prevalence of retinopathy and nephropathy in young people (aged 14-30 yr) with type 1 diabetes in Norway. METHOD: Data on 874 patients were obtained by linking two nationwide, population-based medical quality registries: The Norwegian Diabetes Register for Adults and The Norwegian Childhood Diabetes Registry. RESULTS: Median age was 23 yr, median diabetes duration 9 yr and 51% were male. Median HbA1c increased through adolescence to peak at ages of 17 yr for females and 19 yr for males, females had higher HbA1c than males: 9.3% (78 mmol/mol) vs. 9.1% (76 mmol/mol). Subsequently, median HbA1c declined but was still >8% (>64 mmol/mol) for patients approaching 30 yr. Half of the patients aged 14-17 yr and 40% of patients aged 18-25 yr had HbA1c >9% (75 mmol/mol). Retinopathy was found in 16% and nephropathy in 13% of the population. Patients transferring from the pediatric department to adult care between the ages of 14 and 17 yr had higher median HbA1c and prevalence of late complications than those transferring at ages 18-22 yr. Less than 40% of patients with albuminuria were treated with ACE inhibitors or angiotensin II receptor blocker. CONCLUSION: Our results demonstrate that treatment of adolescents and young adults with type 1 diabetes in Norway is not optimal, especially for patients in their late teens. We suggest that pediatricians and endocrinologists should critically assess the care offered to this group and consider new approaches to help them improve glycemic control. PMID- 26875588 TI - Assessment of the influence of intrinsic environmental and geographical factors on the bacterial ecology of pit latrines. AB - Improving the rate and extent of faecal decomposition in basic forms of sanitation such as pit latrines would benefit around 1.7 billion users worldwide, but to do so requires a major advance in our understanding of the biology of these systems. As a critical first step, bacterial diversity and composition was studied in 30 latrines in Tanzania and Vietnam using pyrosequencing of 16S rRNA genes, and correlated with a number of intrinsic environmental factors such as pH, temperature, organic matter content/composition and geographical factors. Clear differences were observed at the operational taxonomic unit, family and phylum level in terms of richness and community composition between latrines in Tanzania and Vietnam. The results also clearly show that environmental variables, particularly substrate type and availability, can exert a strong structuring influence on bacterial communities in latrines from both countries. The origins and significance of these environmental differences are discussed. This work describes the bacterial ecology of pit latrines in combination with inherent latrine characteristics at an unprecedented level of detail. As such, it provides useful baseline information for future studies that aim to understand the factors that affect decomposition rates in pit latrines. PMID- 26875590 TI - Mortality risk in post-transplantation diabetes mellitus based on glucose and HbA1c diagnostic criteria. AB - Current diagnostic criteria for post-transplantation diabetes mellitus (PTDM) are either fasting plasma glucose >=7.0 mmol/l (>=126 mg/dl) or postchallenge plasma glucose >=11.1 mmol/l (>=200 mg/dl) 2 h after glucose administration [oral glucose tolerance test (OGTT) criterion]. In this retrospective cohort study of 1632 renal transplant recipients (RTRs) without known diabetes mellitus at the time of transplantation, we estimated mortality hazard ratios for patients diagnosed with PTDM by either conventional glucose criteria or the proposed glycated haemoglobin (HbA1c) criterion [HbA1c >=6.5% (>=48 mmol/mol)]. During a median follow-up of 7.0 years, 311 patients died. Compared with nondiabetic patients and after adjustment for confounders, patients diagnosed with PTDM based on chronic hyperglycaemia early after transplantation (manifest PTDM) or by the OGTT criterion at 10 weeks post-transplant suffered a higher mortality risk (HR 1.59, 95% CI 1.06-2.38, P = 0.02 and HR 1.56, 95% CI 1.04-2.38, P = 0.03, respectively). In contrast, patients diagnosed with PTDM by the HbA1c criterion at 10 weeks or between 10 weeks and 1 year post-transplant were not associated with mortality (HR 0.96, 95% CI 0.61-1.51, P = 0.86 and 1.58, 95% CI 0.74-3.36, P = 0.24 respectively). After adjustment for confounders and competing risks, only patients with manifest PTDM had a significantly higher cardiovascular mortality risk (subdistributional HR 2.31, 95% CI 1.19-4.47, P < 0.001). Since many cases with PTDM were only identified by the OGTT, we recommend monitoring fasting plasma glucose early after renal transplantation followed by an OGTT at 2-3 months post-transplant in patients without overt diabetes mellitus. PMID- 26875591 TI - Evaluation of propensity scores, disease risk scores, and regression in confounder adjustment for the safety of emerging treatment with group sequential monitoring. AB - PURPOSE: The objective of this study was to evaluate regression, matching, and stratification on propensity score (PS) or disease risk score (DRS) in a setting of sequential analyses where statistical hypotheses are tested multiple times. METHODS: In a setting of sequential analyses, we simulated incident users and binary outcomes with different confounding strength, outcome incidence, and the adoption rate of treatment. We compared Type I error rate, empirical power, and time to signal using the following confounder adjustments: (i) regression; (ii) treatment matching (1:1 or 1:4) on PS or DRS; and (iii) stratification on PS or DRS. We estimated PS and DRS using lookwise and cumulative methods (all data up to the current look). We applied these confounder adjustments in examining the association between non-steroidal anti-inflammatory drugs and bleeding. RESULTS: Propensity score and DRS methods had similar empirical power and time to signal. However, DRS methods yielded Type I error rates up to 17% for 1:4 matching and 15.3% for stratification methods when treatment and outcome were common and confounding strength with treatment was stronger. When treatment and outcome were not common, stratification on PS and DRS and regression yielded 8-10% Type I error rates and inflated empirical power. However, when outcome and treatment were common, both regression and stratification on PS outperformed other matching methods with Type I error rates close to 5%. CONCLUSIONS: We suggest regression and stratification on PS when the outcomes and/or treatment is common and use of matching on PS with higher ratios when outcome or treatment is rare or moderately rare. PMID- 26875592 TI - An Analysis of UCNS Certified Headache Center Patient Intake Forms. AB - OBJECTIVE: Compare the similarities and differences among headache intake forms from headache centers with United Council of Neurologic Subspecialties (UCNS) accredited headache medicine fellowships in the United States. Patient intake forms establish a first communication with patients. There have been no studies evaluating them at headache centers. Analysis of these forms can provide insight into their content and potential for improvement. METHODS: This observational study involved collection and analysis of intake forms from 25 UCNS fellowship accredited headache centers from July 2014 to October 2014. Forms were compared and contrasted in terms of data fields included, response format, and use of validated assessment tools. RESULTS: Forms shared many common elements, yet were highly variable in content, style, scales, and methods of analysis. Twenty percent (5/20) of centers did not have a formal intake form. Forms ranged from 1 to 28 pages. Seventy percent (12/17) utilized a check box format, 23% (4/17) utilized an open ended/fill in the blank format, and 6% (1/17) utilized a circle the response(s) format. Family history was inquired about in 82% (14/17) of forms and past medical history (PMH) in 58% (10/17) of forms. Gender questions were asked 82% (14/17) of the time for women, 29% (5/17) for men. Eighty-eight percent (15/17) of forms had questions concerning any type of previous medication tried. DISCUSSION: Patient intake forms are useful for clinical purposes, but vary markedly between UCNS headache centers. Ultimately, a universal intake form could be generated, providing a research-based alternative to the form currently used at each center. Use of a standardized intake form by UCNS centers would streamline data collection, a good first step in the eventual generation of a headache registry. PMID- 26875593 TI - Vein graft thrombi, a niche for smooth muscle cell colonization - a hypothesis to explain the asymmetry of intimal hyperplasia. AB - Essentials Vein graft failure is the most frequent late onset complication of coronary artery bypass grafting. Cuff technique-based interposition mouse model including new anticoagulation regime was conducted. Early vein graft thrombi may serve as a niche for smooth muscle cell colonization. The focal character of early thrombi may form the basis for the asymmetry of intimal hyperplasia. SUMMARY: Background Autologous saphenous veins are widely used in coronary artery bypass grafting; however, 10 years after surgery, 40% of grafts are completely occluded, and another 30% show reduced blood flow. Objective In the past, the central processes and signaling pathways responsible for this loss of patency have been identified. However, one central finding in the process of graft failure is so far not understood: the asymmetric character of intimal hyperplasia. It was the goal of the present study to address this aspect. Methods By the use of a cuff technique-based vein interposition mouse model with a new anticoagulation regime, alterations in vein grafts were analyzed 1 h, 1 day, 2 days, 3 days, 7 days and 21 days after reperfusion by means of immunolabeling, histochemistry, and high-resolution ultrasound. Results The novel and major finding of this study is that the vein graft thrombus may serve as a niche that is infiltrated and colonized by smooth muscle cells (SMCs). Fibroblast growth factor-1 and platelet-derived growth factor-B may be the SMC-attracting factors in the thrombus. The focal character of early thrombi may define the focal and asymmetric character of vein graft intimal hyperplasia. Conclusions Inhibiting the formation and reducing the size of early thrombi is an old concept for reducing vein graft failure. However, in light of the present new findings obtained under a clinic-like anticoagulation regime, early vein graft thrombus prevention/size reduction should be revisited in the prevention of graft failure. PMID- 26875594 TI - Reply: Choroidal thickness shows diurnal variation. PMID- 26875595 TI - Spermiophages on testicular fine needle aspiration cytology: A rare finding. AB - Macrophages usually reside in the testicular interstitial tissues and are normally not found within the seminiferous tubules. However, in certain cases of male infertility, the macrophages are activated and can then be found within the tubules where they can ingest spermatozoa and are labeled as "spermiophages." FNAC was performed in a 36 year male with history of primary infertility. On microscopy, smears made from right testis were indicative of hypospermatogenesis. On the contrary, smears made from the left testis were very cellular showing Sertoli cells and the entire spectrum of normal spermatogenesis. Also seen were many isolated spermiophages. The cytological impression given for the left testis was normal spermatogenesis with numerous spermiophages. Thus the patient fell in the category of obstructive azoospermia (OA). According to currently adopted hypothesis, macrophages carry ingested sperm heads with some antigenic components to the basal capillaries which may result in the formation of autoantibodies against the spermatozoa. This situation may further diminish the chances of fertility in men. The origin of these spermiophage cells is unknown. Although commonly reported in semen and epididymal biopsies, they have not been reported to occur on testicular fine needle aspiration cytology (FNAC). In our case, no sperms were found on semen examination which were easily picked up on testicular FNAC indicating usefulness of the latter in the diagnosis of cases of male infertility and eliminating the need for a testicular biopsy. PMID- 26875596 TI - Two cases of primary non-Hodgkin's lymphoma of female breast: Role of fine-needle aspiration cytology and cell-block immunohistochemistry. AB - Primary breast lymphoma (PBL) is an uncommon neoplastic condition. Though HIV infection is a known risk factor for the development of extranodal lymphomas, mammary involvement is still a rarity. Radiologically, PBL appears as well circumscribed, heteroechoic, noncalcifying mass. Fine-needle aspiration cytology (FNAC) is commonly used to diagnose this neoplasm; however, subcategorization requires immunophenotypic characterization of the neoplastic cells. Herein, we report two cases of PBL, including a HIV-infected lady; in both the cases FNAC expressed features of non-Hodgkin's lymphoma. Finally, immunohistochemistry on cell-block with CD20 diagnosed both the cases as diffuse large B-cell lymphoma (DLBCL). PMID- 26875597 TI - Cytology of low-grade cribriform cystadenocarcinoma in salivary glands: Cytological and immunohistochemical distinctions from other salivary gland neoplasms. AB - Low-grade cribriform cystadenocarcinoma of the parotid gland is rare malignancy that is classified as a variant of cystadenocarcinoma. In routine cytologic slides from fine-needle aspiration of a parotid gland, we found several pseudopapillary clusters comprising mucus-producing cells. They included a few tumor cells having three-dimensional nuclear atypia and slight hyperchromatism, although most of the tumor cells showed bland nuclei. Our initial cytological diagnosis was: "Indeterminate. Uncertain whether cystadenocarcinoma or cystadenoma." The subsequent histological diagnosis was low-grade cribriform cystadenocarcinoma. Immunohistochemical staining showed diffuse and strong reactivity for S-100; tumor nests that were rimmed by p63(+) cells, which suggests intraductal proliferation. Here, we report cytomorphological findings of this case, and discuss cytological and immunohistochemical distinctions between low-grade cribriform cystadenocarcinoma and other salivary gland tumors, including a review of the literature. PMID- 26875598 TI - Associations of Total and Domain-Specific Sedentary Time With Type 2 Diabetes in Taiwanese Older Adults. AB - BACKGROUND: The increasing prevalence of type 2 diabetes in older adults has become a public health concern. We investigated the associations of total and domain-specific sedentary time with risk of type 2 diabetes in older adults. METHODS: The sample comprised 1046 older people (aged >=65 years). Analyses were performed using cross-sectional data collected via computer-assisted telephone based interviews in 2014. Data on six self-reported domains of sedentary time (Measure of Older Adults' Sedentary Time), type 2 diabetes status, and sociodemographic variables were included in the study. Binary logistic regression analysis was performed to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for total and individual sedentary behavior components and likelihood of type 2 diabetes. RESULTS: A total of 17.5% of the participants reported type 2 diabetes. No significant associations were found between total sitting time and risk of type 2 diabetes, after controlling for confounding factors. After total sedentary behavior was stratified into six domains, only watching television for more than 2 hours per day was associated with higher odds of type 2 diabetes (OR 1.56; 95% CI, 1.10-2.21), but no significant associations were found between other domains of sedentary behavior (computer use, reading, socializing, transport, and hobbies) and risk of type 2 diabetes. CONCLUSIONS: These findings suggest that, among domain-specific sedentary behavior, excessive television viewing might increase the risk of type 2 diabetes among older adults more than other forms of sedentary behavior. PMID- 26875599 TI - Five-Year Progression of Refractive Errors and Incidence of Myopia in School-Aged Children in Western China. AB - BACKGROUND: To determine the change in refractive error and the incidence of myopia among school-aged children in the Yongchuan District of Chongqing City, Western China. METHODS: A population-based cross-sectional survey was initially conducted in 2006 among 3070 children aged 6 to 15 years. A longitudinal follow up study was then conducted 5 years later between November 2011 and March 2012. Refractive error was measured under cycloplegia with autorefraction. Age, sex, and baseline refractive error were evaluated as risk factors for progression of refractive error and incidence of myopia. RESULTS: Longitudinal data were available for 1858 children (60.5%). The cumulative mean change in refractive error was -2.21 (standard deviation [SD], 1.87) diopters (D) for the entire study population, with an annual progression of refraction in a myopic direction of 0.43 D. Myopic progression of refractive error was associated with younger age, female sex, and higher myopic or hyperopic refractive error at baseline. The cumulative incidence of myopia, defined as a spherical equivalent refractive error of -0.50 D or more, among initial emmetropes and hyperopes was 54.9% (95% confidence interval [CI], 45.2%-63.5%), with an annual incidence of 10.6% (95% CI, 8.7%-13.1%). Myopia was found more likely to happen in female and older children. CONCLUSIONS: In Western China, both myopic progression and incidence of myopia were higher than those of children from most other locations in China and from the European Caucasian population. Compared with a previous study in China, there was a relative increase in annual myopia progression and annual myopia incidence, a finding which is consistent with the increasing trend on prevalence of myopia in China. PMID- 26875600 TI - Dynamic changes in CD45RA(-)Foxp3(high) regulatory T-cells in chronic hepatitis C patients during antiviral therapy. AB - OBJECTIVES: CD4(+)Foxp3(+) regulatory T-cells (Treg) are known to accumulate under certain pathological conditions. This study was conducted to evaluate the characteristics of and dynamic changes in Treg cells in chronic hepatitis C (CHC) patients during antiviral therapy. METHODS: One hundred and forty-five subjects were enrolled in this study, including 105 CHC patients and 40 healthy donors. The phenotypes and functions of Treg cells were analyzed by flow cytometry. RESULTS: A significant elevation in Treg cells was observed in the peripheral blood of CHC patients compared with healthy donors. Interestingly, compared with non-suppressive Treg (non-Treg) and resting Treg (rTreg) cells, activated Treg (aTreg) cells expressed higher levels of ectonucleotidase, CD39, and CD73. After treatment with interferon alpha (IFN-alpha) and ribavirin (RBV) in vitro, the frequencies of total Treg cells and aTreg cells in peripheral blood mononuclear cells (PBMC), as well as the levels of transforming growth factor beta (TGF-beta) secreted by aTreg and non-Treg cells, were significantly decreased. Importantly, it was found that levels of aTreg cells in patients with a sustained virological response (SVR) were lower than in relapsed patients, suggesting that a high frequency of aTreg cells might be associated with a poor clinical outcome in HCV infection. CONCLUSION: These results demonstrate a decreasing trend in aTreg cells, which express higher levels of CD39, CD73, and TGF-beta, in SVR patients during antiviral therapy. PMID- 26875601 TI - The epidemiology of Middle East respiratory syndrome coronavirus in the Kingdom of Saudi Arabia, 2012-2015. AB - OBJECTIVES: The aim of this study was to review the epidemiology of cases of Middle East respiratory syndrome coronavirus (MERS-CoV) reported in the Kingdom of Saudi Arabia from 2012 when the first MERS-CoV was confirmed up to July 2015. METHODS: MERS-CoV data were obtained from the Saudi Ministry of Health for the period 2012 to July 2015. Descriptive statistics were used to summarize the results regarding the risk factors and mortality of MERS-CoV infection. RESULTS: In this series, the risk factors and outcomes of 939 cases of MERS-CoV occurring in the last 3 years are described. The majority of the affected patients were aged >=40 years (n=657; 70%). Of the 657 patients aged >=40 years, 377 (57.3%) died. CONCLUSIONS: The case-fatality ratio was found to increase significantly with age. It ranged from 12.5% in those aged <=19 years to 86.2% in those aged >=80 years. The results confirmed the association between severe MERS-CoV illness and patients with a pre-existing health morbidity. The duration from symptom onset to admission was not statistically associated with the disease outcome. PMID- 26875602 TI - An INCA model for pathogens in rivers and catchments: Model structure, sensitivity analysis and application to the River Thames catchment, UK. AB - Pathogens are an ongoing issue for catchment water management and quantifying their transport, loss and potential impacts at key locations, such as water abstractions for public supply and bathing sites, is an important aspect of catchment and coastal management. The Integrated Catchment Model (INCA) has been adapted to model the sources and sinks of pathogens and to capture the dominant dynamics and processes controlling pathogens in catchments. The model simulates the stores of pathogens in soils, sediments, rivers and groundwaters and can account for diffuse inputs of pathogens from agriculture, urban areas or atmospheric deposition. The model also allows for point source discharges from intensive livestock units or from sewage treatment works or any industrial input to river systems. Model equations are presented and the new pathogens model has been applied to the River Thames in order to assess total coliform (TC) responses under current and projected future land use. A Monte Carlo sensitivity analysis indicates that the input coliform estimates from agricultural sources and decay rates are the crucial parameters controlling pathogen behaviour. Whilst there are a number of uncertainties associated with the model that should be accounted for, INCA-Pathogens potentially provides a useful tool to inform policy decisions and manage pathogen loading in river systems. PMID- 26875603 TI - Managing coastal environments under climate change: Pathways to adaptation. AB - This paper deals with the question of how to manage vulnerable coastal systems so as to make them sustainable under present and future climates. This is interpreted in terms of the coastal functionality, mainly natural services and support for socio-economic activities. From here we discuss how to adapt for long term trends and for short terms episodic events using the DPSIR framework. The analysis is presented for coastal archetypes from Spain, Ireland and Romania, sweeping a range of meteo-oceanographic and socio-economic pressures, resulting in a wide range of fluxes among them those related to sediment. The analysis emphasizes the variables that provide a higher level of robustness. That means mean sea level for physical factors and population density for human factors. For each of the studied cases high and low sustainability practices, based on stakeholders preferences, are considered and discussed. This allows proposing alternatives and carrying out an integrated assessment in the last section of the paper. This assessment permits building a sequence of interventions called adaptation pathway that enhances the natural resilience of the studied coastal systems and therefore increases their sustainability under present and future conditions. PMID- 26875604 TI - Assessing the capacity of zero valent iron nanofluids to remediate NAPL-polluted porous media. AB - A variety of aqueous suspensions (nanofluids) of zero-valent nano-particles (nZVI) are prepared by wet chemistry techniques, their stability and longevity is evaluated by physic-chemical methods of characterization, and their reactivity toward the dechlorination of per-chloro-ethylene (PCE) is examined with tests in batch reactors. For assessing the mobility, longevity and reactivity of nZVI suspensions (nanofluids), under flow-through conditions, visualization multiphase flow and transport tests are performed on a glass-etched pore network. The nZVI breakthrough curves are constructed by measuring the transient variation of the iron concentration in the effluent with atomic absorption spectroscopy. The capacity of nZVI to remediate the bulk phase of PCE is quantified by detecting the mass loss rate of PCE ganglia trapped in glass-etched pore networks during the continuous injection of nZVI suspension or pure water. The nZVI injection in porous media is simulated as an advection- dispersion process by accounting for the attachment/detachment of nanoparticles on the pore-walls, and describing the kinetics of PCE dissolution and reaction by 1st order equations. Visualization experiments reveal that the gradual elimination of PCE ganglia by the injected nZVI is associated with the preferential "erosion" of the upstream interfacial regions. The step controlling the overall process kinetics might be either (i) the enhanced PCE dissolution or (ii) the direct reaction of bulk PCE with the nZVI deposited upon the ganglia interfaces. Inverse modeling of the experiments under the simplifying assumption of one active mechanism indicates that the estimated kinetic coefficients are increasing functions of the flow rate. PMID- 26875605 TI - Major and trace elements in soils and ashes of eucalypt and pine forest plantations in Portugal following a wildfire. AB - Wildfires can play an important role in the environmental distribution of major and trace elements, including through their mobilization by fire-induced runoff and associated transport of soil and ash particles. In particular, fire-induced inputs of these elements into the environment are relevant due to their toxicity and environmental persistence. This study aimed to evaluate the role of wildfire and time-since-fire on the redistribution of major and trace elements, which is a topic poorly documented. To this end, levels of V, Mn, Co, Ni, Cu, Cd and Pb were assessed in soil and ash samples collected immediately following a wildfire in north-central Portugal as well as 4 (after the first post-fire rainfall events), 8 and 15months later. The role of forest type was determined by sampling burnt eucalypt and pine plantations. The main findings of this study were the following: (1) levels of V, Mn, Ni, Cd and Pb were consistently higher in the burnt than unburnt soils, while levels of Co and Cu revealed no differences; (2) time-since-fire affected major and trace elements in three different ways: concentrations of Mn and Cd declined abruptly after the first rainfall events while levels of V, Co and Ni increased during the first 8months and levels of Cu and Pb hardly changed during the study period; (3) all studied elements revealed peak concentrations in the ashes immediately after the fire, which then declined sharply four months later; (4) levels of Co and Ni soils and ashes were higher at the pine plantations than at the eucalypt plantations. This study highlighted the role of wildfire in enhancing levels of major and trace elements in ashes and topsoil of forest plantations and their mobilization within the first year after fire, pointing towards recently burnt forest areas as a potential source of environmental contamination. PMID- 26875606 TI - Human annoyance, acceptability and concern as responses to vibration from the construction of Light Rapid Transit lines in residential environments. AB - The aim of this paper is to investigate the use of different self-reported measures for assessing the human response to environmental vibration from the construction of an urban LRT (Light Rapid Transit) system. The human response to environmental stressors such as vibration and noise is often expressed in terms of exposure-response relationships that describe annoyance as a function of the magnitude of the vibration. These relationships are often the basis of noise and vibration policy and the setting of limit values. This paper examines measures other than annoyance by expressing exposure-response relationships for vibration in terms of self-reported concern about property damage and acceptability. The exposure-response relationships for concern about property damage and for acceptability are then compared with those for annoyance. It is shown that concern about property damage occurs at vibration levels well below those where there is any risk of damage. Earlier research indicated that concern for damage is an important moderator of the annoyance induced. Acceptability, on the other hand, might be influenced by both annoyance and concern, as well as by other considerations. It is concluded that exposure-response relationships expressing acceptability as a function of vibration exposure could usefully complement existing relationships for annoyance in future policy decisions regarding environmental vibration. The results presented in this paper are derived from data collected through a socio-vibration survey (N=321) conducted for the construction of an urban LRT in the United Kingdom. PMID- 26875607 TI - On the question of adjustment for multiple testing. PMID- 26875608 TI - Impact of Malaria in Pregnancy as Latin America Approaches Elimination. AB - In Latin America, four million pregnancies are at risk of malaria annually, but malaria in pregnancy is largely overlooked. As countries progress toward malaria elimination, targeting reservoirs of transmission is a priority. Pregnant women are an important risk group because they harbor asymptomatic infections and dormant liver stages of Plasmodium vivax that cause relapses. Of significant concern is the discovery that most infections in pregnant women fail to be detected by routine diagnostics. We review here recent findings on malaria in pregnancy within Latin America. We focus on the Amazon basin and Northwest Colombia, areas that harbor the greatest burden of malaria, and propose that more sensitive diagnostics and active surveillance at antenatal clinics will be necessary to eliminate malaria from these final frontiers. PMID- 26875609 TI - Zinc finger protein A20 is involved in the antipsoriatic effect of calcipotriol. AB - BACKGROUND: Calcipotriol ameliorates psoriasis through inducing keratinocyte apoptosis and inhibiting nuclear factor kappa B (NF-kappaB) activation, while zinc finger protein A20 exhibits an anti-apoptotic effect on various types of cells. OBJECTIVES: To understand the potential role of A20 in calcipotriol function. MATERIALS AND METHODS: The A20 levels were evaluated in the psoriatic skins from both human patients and K14-vascular endothelial growth factor (VEGF) transgenic mice that received or did not receive topical calcipotriol treatment. The in vitro effect of calcipotriol on A20 expression and the downstream NF kappaB pathway was studied using a model of human foreskin keratinocytes (HFKs) that were stimulated with psoriatic cytokines [M5, a cocktail of interleukin (IL) 1a, IL-17A, IL-22, Oncostatin M and tumour necrosis factor-alpha, each at 10 ng mL(-1) ]. RESULTS: A20 expression was enhanced in both psoriatic tissues and keratinocytes when compared with controls, but decreased on calcipotriol treatment. The transfection of A20 small interfering RNA (siRNA) improved cell differentiation, and inhibited psoriatic inflammation in a HFK model. Moreover, the nuclear expression of NF-kappaB p65 decreased on A20 downregulation in psoriatic tissues and keratinocytes. Interestingly, calcipotriol enhanced the binding of A20 to ring finger protein 114 (RNF114) and A20-binding inhibitor of NF-kappaB-1 (ABIN-1) in HFKs, two negative regulators of the NF-kappaB pathway. CONCLUSIONS: Calcipotriol exhibits its antipsoriatic function through suppressing A20 expression and stabilizing negative regulators of the NF-kappaB pathway. PMID- 26875610 TI - Open access to journal articles in dentistry: Prevalence and citation impact. AB - OBJECTIVES: To investigate the current prevalence of open access (OA) in the field of dentistry, the means used to provide OA, as well as the association between OA and citation counts. METHODS: PubMed was searched for dental articles published in 2013. The OA status of each article was determined by manually checking Google, Google Scholar, PubMed and ResearchGate. Citation data were extracted from Google Scholar, Scopus and Web of Science. Chi-square tests were used to compare the OA prevalence by different subjects, study types, and continents of origin. The association between OA and citation count was studied with multivariable logistic regression analyses. RESULTS: A random sample of 908 articles was deemed eligible and therefore included. Among these, 416 were found freely available online, indicating an overall OA rate of 45.8%. Significant difference in OA rate was detected among articles in different subjects (P<0.001) and among those from different continents (P<0.001). Of articles that were OA, 74.2% were available via self-archiving ('Green road' OA), 53.3% were available from publishers ('Gold road' OA). According to multivariable logistic regression analyses, OA status was not significantly associated with either the existence of citation (P=0.37) or the level of citation (P=0.52). CONCLUSIONS/CLINICAL SIGNIFICANCE: In the field of dentistry, 54% of recent journal articles are behind the paywall (non-OA) one year after their publication dates. The 'Green road' of providing OA was more common than the 'Gold road'. No evidence suggested that OA articles received significantly more citations than non-OA articles. PMID- 26875611 TI - Clinical performance of anterior resin-bonded fixed dental prostheses with different framework designs: A systematic review and meta-analysis. AB - OBJECTIVES: To systematically review the failure rate and complications of different framework designs of resin-bonded fixed dental prostheses (RBFDPs) in the anterior region. METHODS: A systematic search for clinical studies on RBFDPs published prior to December 2014 in Medline/PubMed, EMBASE, and Cochrane Library databases was conducted and complemented by a manual search. Randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies that compared at least two RBFDP framework designs with a minimum of 2 years follow up were included in this review. The quality of the included studies were assessed using the Newcastle-Ottawa scale for cohort studies and Cochrane Handbook for RCT. Prostheses-based data on reported failure rate/survival rate, debonding, and fractures were analyzed by meta-analysis. RESULTS: Of 1010 screened articles, one RCT and 4 cohort studies fit the inclusion criteria and were included in the meta-analysis. All included articles have a high risk of bias. Failure rates of single-retainer cantilever RBFDPs were lower than two retainer fixed-fixed RBFDPs (OR 0.42, 95% CI 0.19-0.94, P=0.04). Metal-ceramic RBFDPs showed no difference of failure rates between cantilever RBFDPs and two retainer fixed-fixed RBFDPs (OR 0.93, 95% CI 0.33-2.63, P=0.89). Debonding was not significantly different between cantilever RBFDPs and two-retainer fixed fixed RBFDPs (OR 0.61, 95% CI 0.23-1.60, P=0.32). Metal-ceramic RBFDPs showed no difference of debonding between cantilever RBFDPs and two-retainer fixed-fixed RBFDPs (OR 0.81, 95% CI 0.28-2.34, P=0.70,). CONCLUSIONS: Within the limitations of the present study, cantilever RBFDPs demonstrate lower clinical failure than two-retainer RBFDPs in the anterior region. The failure of metal-ceramic RBFDPs is independent of the framework design, while the failure of all-ceramic RBFDPs with different designs has not been clear yet. CLINICAL SIGNIFICANCE: Based on the principle of minimally invasive treatment, less number of retainers is recommended for RBFDPs. PMID- 26875612 TI - Influence of removing excess of resin-based materials applied to eroded enamel on the resistance to erosive challenge. AB - OBJECTIVES: The aim of this study was to evaluate the effect of removing excess of resin-based materials applied to eroded enamel, subjected to erosive challenge. METHODS: Bovine enamel blocks were immersed in HCl 0.01M, pH 2.3, for 30s under agitation at 50 rpm in room temperature, in order to form a softened erosion lesion. The blocks were then randomly divided into eight groups (n=12) and treated as follows: Cn- and Ce-control without treatment, Hn- and He-fissure resin sealant (Helioseal Clear((r))), An- and Ae-self-etch adhesive (Adhese((r))), In- and Ie-infiltrant (Icon((r))); being n-with excess removal and e-without excess removal of the material. After application of the materials, the blocks were immersed in HCl for 2 min, followed by immersion in artificial saliva for 120 min. This cycle was repeated four times a day for five days. Material thickness and enamel wear were assessed using profilometry. Data were analyzed by two-way ANOVA and Tukey's test (P<0.05). RESULTS: Groups He, Ae, and Ie resulted in the formation of a layer of material over enamel, being similar effective in inhibiting erosion progression (P>0.05). Groups Hn, An, and In (with excess removal) were similar to controls (Cn, Ce) and resulted in near enamel loss after application and after erosive challenge (P>0.05). CONCLUSIONS: Resin-based materials are able to protect enamel against erosion only when they are present over enamel, as a physical barrier. CLINICAL SIGNIFICANCE: The resin-based materials demonstrated potential to prevent the progression of erosion lesions when the material remains on the dental surface. PMID- 26875613 TI - Antimicrobial effects of commensal oral species are regulated by environmental factors. AB - OBJECTIVES: The objectives of this study are to identify oral commensal species which can inhibit the growth of the main periodontopathogens, to determine the antimicrobial substances involved in these inhibitory activities and to evaluate the influence of environmental factors on the magnitude of these inhibitions. METHODS: The spotting technique was used to quantify the capacity of 13 commensal species to inhibit the growth of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia. By altering experimental conditions (distance between spots and size of spots and concentration of commensal and pathogen) as well as environmental factors (inoculation sequence, oxygen and nutrition availability) the influence of these factors was evaluated. Additionally, the mechanism of inhibition was elucidated by performing inhibition experiments in the presence of peroxidase, trypsin and pepsin and by evaluating acid production. RESULTS: Streptococcus sanguinis, Streptococcus cristatus, Streptococcus gordonii, Streptococcus parasanguinis, Streptococcus mitis and Streptococcus oralis significantly inhibit the growth of all pathogens. The volume of the spots and concentration of the commensal have a significant positive correlation with the amount of inhibition whereas distance between the spots and concentration of the pathogen reduced the amount of inhibition. Inhibition is only observed when the commensal species are inoculated 24h before the pathogen and is more pronounced under aerobic conditions. Hydrogen peroxide production by the commensal is the main mechanism of inhibition. CONCLUSION: Bacterial antagonism is species specific and depending on experimental as well as environmental conditions. Blocking hydrogen peroxide production neutralizes the inhibitory effect. CLINICAL SIGNIFICANCE: Identifying beneficial oral bacteria and understanding how they inhibit pathogens might help to unravel the mechanisms behind dysbiotic oral diseases. In this context, this study points towards an important role for hydrogen peroxide. The latter might lead in the future to novel preventive strategies for oral health based on improving the antimicrobial properties of commensal oral bacteria. PMID- 26875614 TI - Long-term anti-cariogenic biofilm activity of glass ionomers related to fluoride release. AB - OBJECTIVES: The aim of this study was to evaluate the difference between anti cariogenic biofilm activities of glass ionomers (G-Is) during the initial and second fluoride release phases and to define relationships between the anti biofilm activities and fluoride release. METHODS: Fluoride release of three commercially available G-Is in a buffer was evaluated for 770 h, and then 70-h old Streptococcus mutans UA159 biofilms were formed on the G-Is that had been immersed in the buffer for 0, 100, 200, or 700 h. The dry weight, bacterial cell number, water-insoluble extracellular polysaccharides (EPSs), and accumulated fluoride concentration of the 70-h-old biofilms and fluoride release and acid production rates during biofilm formation were determined. Relationships between the experimental variables and fluoride release rate were also evaluated using linear regression analysis. RESULTS: In this study, fluoride release of the tested G-Is did not exhibit a biphasic pattern during biofilm formation. The release was sustained or did not rapidly decrease even over long immersion periods and was strongly correlated with an increase in accumulated fluoride concentration of the biofilms (R=0.99, R(2)=0.98) and reductions in dry weight, water-insoluble EPSs, and acid production rate of the biofilms (R=-0.99 to -0.96, R(2)=0.92-0.98). CONCLUSIONS: This study suggests that G-Is can effectively affect acid production, EPS formation, and accumulation of cariogenic biofilms even during the second fluoride release phase, and that the anti-cariogenic biofilm activity is strongly correlated with fluoride release, which may be enhanced by acid production of cariogenic biofilms. CLINICAL SIGNIFICANCE: G-Is can affect cariogenic biofilm formation even during the second fluoride release phase. PMID- 26875615 TI - The liability of the anaesthesiologist in ambulatory surgery. AB - With the development of ambulatory surgery, there may be questions about the legal risk of this procedure. Indeed, the discharge of the patient from the hospital on the same day as the medical treatment raises the problem of monitoring and supervising potential complications, with a substantial delay in medical care, and the anaesthesiologists can be confronted with new areas of liability. This article specifies the French statutory and legal framework of the ambulatory surgery, and shows how the responsibility of the anaesthesiologist can be involved during patient care at all steps. The analysis of judicial precedent shows that the legal risk for the anaesthesiologist also exists in outpatient surgery. Surgery and anaesthesia are medical procedures involving a relatively high risk of damage for the patient. The damage can be attributed to malpractice from one or several health care professionals or to a medical complication (abnormal damage not related to malpractice and independent of past medical history of the patient). In the light of the ongoing and significant development in ambulatory surgery, there may be questions about the legal risk of this procedure. Indeed, the discharge of the patient from the hospital on the same day as the medical treatment raises the problem of monitoring and supervising potential complications, with a substantial delay in medical care. If the patient suffers any damage, the surgeon, the anaesthesiologist and in some cases, the hospital will have to answer in courts: the surgeon for the surgical procedure, the anaesthesiologist for the medical care and the hospital as the liable institution. After having specified the statutory framework of ambulatory surgery, we will see how the responsibility of the anaesthesiologist can be involved during patient care at all steps. PMID- 26875616 TI - Inosine-5'-monophosphate is a candidate agent to resolve rigor mortis of skeletal muscle. AB - The object of the present study was to reveal the action of inosine-5' monophosphate (IMP) toward myofibrils in postmortem muscles. IMP solubilized isolated actomyosin within a narrow range of KCl concentration, 0.19-0.20 mol/L, because of the dissociation of actomyosin into actin and myosin, but it did not solubilize the proteins in myofibrils with 0.2 mol/L KCl. However, IMP could solubilize both proteins in myofibrils with 0.2 mol/L KCl in the presence of 1 m mol/L pyrophosphate or 1.0-3.3 m mol/L adenosine-5'-diphosphate (ADP). Thus, we presumed that pyrophosphate and ADP released thin filaments composed of actin, and thick filaments composed of myosin from restraints of myofibrils, and then both filaments were solubilized through the IMP-induced dissociation of actomyosin. Thus, we concluded that IMP is a candidate agent to resolve rigor mortis because of its ability to break the association between thick and thin filaments. PMID- 26875618 TI - A Deadly Path: Bacterial Spread During Bubonic Plague. AB - Yersinia pestis causes bubonic plague, a fulminant disease where host immune responses are abrogated. Recently developed in vivo models of plague have resulted in new ideas regarding bacterial spread in the body. Deciphering bacterial spread is key to understanding Y. pestis and the immune responses it encounters during infection. PMID- 26875619 TI - Sharing Data for Global Infectious Disease Surveillance and Outbreak Detection. AB - Rapid global sharing and comparison of epidemiological and genomic data on infectious diseases would enable more rapid and efficient global outbreak control and tracking of diseases. Several barriers for global sharing exist but, in our opinion, the presumed magnitude of the problems appears larger than they are, and solutions can be found. PMID- 26875617 TI - HIV-1 Reservoirs During Suppressive Therapy. AB - The introduction of antiretroviral therapy (ART) 20 years ago has dramatically reduced morbidity and mortality associated with HIV-1. Initially there was hope that ART would be curative, but it quickly became clear that even though ART was able to restore CD4(+) T cell counts and suppress viral loads below levels of detection, discontinuation of treatment resulted in a rapid rebound of infection. This is due to persistence of a small reservoir of latently infected cells with a long half-life, which necessitates life-long ART. Over the past few years, significant progress has been made in defining and characterizing the latent reservoir of HIV-1, and here we review how understanding the latent reservoir during suppressive therapy will lead to significant advances in curative approaches for HIV-1. PMID- 26875620 TI - Long-term adverse effects associated with isolated below-knee deep-vein thrombosis: a 10-year follow-up study. AB - AIM: To assess the effect of the presence and locality of symptomatic lower-limb deep vein thrombosis (DVT) on mortality and morbidity following contrast venography (CV), the reference standard for diagnosing below-knee DVT, with a view to determining the prevalence of recurrent episodes of DVT and post thrombotic syndrome (PTS). MATERIALS AND METHODS: Patients with clinical DVT undergoing investigation using CV were prospectively recorded. By retrospective case note examination and mortality data evaluation, 347 patients with DVT were matched with negative controls for mortality follow-up. Long-term complications were recorded. RESULTS: Fifty-one (14.7%) of the DVT patients were diagnosed with PTS and 43 (12.4%) with possible PTS in the 10 years following presentation. The relative risk for developing definite PTS was 0.544 for below- versus above-knee DVT; 9.9% with below-knee DVT had PTS, and 9% had probable PTS. Recurrent DVT occurred in 23.3% of patients with proximal DVT as opposed to 12.6% of patients with isolated below-knee DVT. CONCLUSIONS: Morbidity is greater in patients with proximal DVT; however, a significant, albeit smaller, proportion of patients with isolated below-knee DVT develop recurrent DVT and PTS. Below-knee DVT carries sufficient morbidity and mortality to warrant vigilance in diagnosis and management of this condition. PMID- 26875621 TI - Differentiation of benign and metastatic axillary lymph nodes in breast cancer: additive value of MRI computer-aided evaluation. AB - AIM: To retrospectively determine the qualitative and quantitative cut-off values of the magnetic resonance computer-aided evaluation (MR CAE) parameters to differentiate between benign and metastatic axillary lymph nodes (ALNs) and to investigate the combined diagnostic performance of MR CAE imaging. MATERIALS AND METHODS: From July 2011 to June 2014, 124 patients who underwent preoperative conventional MR, diffusion-weighted (DW), and MR CAE imaging were included. Computer-generated qualitative and quantitative features for ALNs were recorded, and two breast imaging radiologists interpreted the MR images for the presence of metastatic ALNs using conventional MR and DW, and in combination with MR CAE images by consensus. The cut-off values of MR CAE and diagnostic performance were derived from the receiver operating characteristic (ROC) curve. RESULTS: Thirty four (26.4%) were ALN positive and 90 (73.6%) were ALN negative on the final histopathological result. On qualitative analysis, visualization on the colour map (p=0.007) and kinetic curve type (p<0.001) were significantly different between the groups. On quantitative analysis, mean values (%) of persistent, plateau, and washout ratios differed significantly (p<0.001). Of these significant parameters, a washout ratio of >49% showed the greatest diagnostic accuracy (area under the ROC curve, 0.909). With conventional MR and DW images, sensitivity, specificity, and accuracy were 82.4%, 85.6%, and 84.7%, respectively. With added information from MR CAE images, accuracy significantly improved to 93.5% (p=0.043). The sensitivity and specificity improved to 91.2% (p=0.403) and 94.4% (p=0.086), respectively. CONCLUSION: The additive use of MR CAE improved diagnostic performance and can be helpful for differentiating benign from metastatic ALNs. PMID- 26875622 TI - Brain alpha7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO. AB - Nicotine exerts its behavioral and additive actions through a family of brain nicotinic acetylcholine receptors (nAChRs). Enhancing alpha7-type nAChR signaling improves symptoms in Alzheimer's disease and schizophrenia. The pharmaceutical study of alpha7 receptors is hampered because these receptors do not form their functional pentameric structure in cell lines, and mechanisms that underlie alpha7 receptor assembly in neurons are not understood. Here, a genomic screening strategy solves this long-standing puzzle and identifies NACHO, a transmembrane protein of neuronal endoplasmic reticulum that mediates assembly of alpha7 receptors. NACHO promotes alpha7 protein folding, maturation through the Golgi complex, and expression at the cell surface. Knockdown of NACHO in cultured hippocampal neurons or knockout of NACHO in mice selectively and completely disrupts alpha7 receptor assembly and abolishes alpha7 channel function. This work identifies NACHO as an essential, client-specific chaperone for nAChRs and has implications for physiology and disease associated with these widely distributed neurotransmitter receptors. PMID- 26875623 TI - Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles. AB - Hippocampal neurons activated during encoding drive the recall of contextual fear memory. Little is known about how such ensembles emerge during acquisition and eventually form the cellular engram. Manipulating the activity of granule cells (GCs) of the dentate gyrus (DG), we reveal a mechanism of lateral inhibition that modulates the size of the cellular engram. GCs engage somatostatin-positive interneurons that inhibit the dendrites of surrounding GCs. Our findings reveal a microcircuit within the DG that controls the size of the cellular engram and the stability of contextual fear memory. PMID- 26875624 TI - Post-learning Hippocampal Dynamics Promote Preferential Retention of Rewarding Events. AB - Reward motivation is known to modulate memory encoding, and this effect depends on interactions between the substantia nigra/ventral tegmental area complex (SN/VTA) and the hippocampus. It is unknown, however, whether these interactions influence offline neural activity in the human brain that is thought to promote memory consolidation. Here we used fMRI to test the effect of reward motivation on post-learning neural dynamics and subsequent memory for objects that were learned in high- and low-reward motivation contexts. We found that post-learning increases in resting-state functional connectivity between the SN/VTA and hippocampus predicted preferential retention of objects that were learned in high reward contexts. In addition, multivariate pattern classification revealed that hippocampal representations of high-reward contexts were preferentially reactivated during post-learning rest, and the number of hippocampal reactivations was predictive of preferential retention of items learned in high reward contexts. These findings indicate that reward motivation alters offline post-learning dynamics between the SN/VTA and hippocampus, providing novel evidence for a potential mechanism by which reward could influence memory consolidation. PMID- 26875625 TI - A Large-Scale Interface for Optogenetic Stimulation and Recording in Nonhuman Primates. AB - While optogenetics offers great potential for linking brain function and behavior in nonhuman primates, taking full advantage of that potential will require stable access for optical stimulation and concurrent monitoring of neural activity. Here we present a practical, stable interface for stimulation and recording of large scale cortical circuits. To obtain optogenetic expression across a broad region, here spanning primary somatosensory (S1) and motor (M1) cortices, we used convection-enhanced delivery of the viral vector, with online guidance from MRI. To record neural activity across this region, we used a custom micro electrocorticographic (MUECoG) array designed to minimally attenuate optical stimuli. Lastly, we demonstrated the use of this interface to measure spatiotemporal responses to optical stimulation across M1 and S1. This interface offers a powerful tool for studying circuit dynamics and connectivity across cortical areas, for long-term studies of neuromodulation and targeted cortical plasticity, and for linking these to behavior. PMID- 26875626 TI - Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. AB - To enhance physiological function of NMDA receptors (NMDARs), we identified positive allosteric modulators (PAMs) of NMDARs with selectivity for GluN2A subunit-containing receptors. X-ray crystallography revealed a binding site at the GluN1-GluN2A dimer interface of the extracellular ligand-binding domains (LBDs). Despite the similarity between the LBDs of NMDARs and AMPA receptors (AMPARs), GluN2A PAMs with good selectivity against AMPARs were identified. Potentiation was observed with recombinant triheteromeric GluN1/GluN2A/GluN2B NMDARs and with synaptically activated NMDARs in brain slices from wild-type (WT), but not GluN2A knockout (KO), mice. Individual GluN2A PAMs exhibited variable degrees of glutamate (Glu) dependence, impact on NMDAR Glu EC50, and slowing of channel deactivation. These distinct PAMs also exhibited differential impacts during synaptic plasticity induction. The identification of a new NMDAR modulatory site and characterization of GluN2A-selective PAMs provide powerful molecular tools to dissect NMDAR function and demonstrate the feasibility of a therapeutically desirable type of NMDAR enhancement. PMID- 26875627 TI - Eosinophilic pustular folliculitis: A published work-based comprehensive analysis of therapeutic responsiveness. AB - Eosinophilic pustular folliculitis (EPF) is a non-infectious inflammatory dermatosis of unknown etiology that principally affects the hair follicles. There are three variants of EPF: (i) classic EPF; (ii) immunosuppression-associated EPF, which is subdivided into HIV-associated (IS/HIV) and non-HIV-associated (IS/non-HIV); and (iii) infancy-associated EPF. Oral indomethacin is efficacious, especially for classic EPF. No comprehensive information on the efficacies of other medical management regimens is currently available. In this study, we surveyed regimens for EPF that were described in articles published between 1965 and 2013. In total, there were 1171 regimens; 874, 137, 45 and 115 of which were applied to classic, IS/HIV, IS/non-HIV and infancy-associated EPF, respectively. Classic EPF was preferentially treated with oral indomethacin with efficacy of 84% whereas topical steroids were preferred for IS/HIV, IS/non-HIV and infancy associated EPF with efficacy of 47%, 73% and 82%, respectively. Other regimens such as oral Sairei-to (a Chinese-Japanese herbal medicine), diaminodiphenyl sulfone, cyclosporin and topical tacrolimus were effective for indomethacin resistant cases. Although the preclusion of direct comparison among cases was one limitation, this study provides a dataset that is applicable to the construction of therapeutic algorithms for EPF. PMID- 26875628 TI - Preventing Cardiovascular Disease. PMID- 26875630 TI - A data mining approach to selecting herbs with similar efficacy: Targeted selection methods based on medical subject headings (MeSH). AB - ETHNO-PHARMACOLOGICAL RELEVANCE: Natural products have long been the most important source of ingredients in the discovery of new drugs. Moreover, since the Nagoya Protocol, finding alternative herbs with similar efficacy in traditional medicine has become a very important issue. Although random selection is a common method of finding ethno-medicinal herbs of similar efficacy, it proved to be less effective; therefore, this paper proposes a novel targeted selection method using data mining approaches in the MEDLINE database in order to identify and select herbs with a similar degree of efficacy. MATERIALS AND METHODS: From among sixteen categories of medical subject headings (MeSH) descriptors, three categories containing terms related to herbal compounds, efficacy, toxicity, and the metabolic process were selected. In order to select herbs of similar efficacy in a targeted way, we adopted the similarity measurement method based on MeSH. In order to evaluate the proposed algorithm, we built up three different validation datasets which contain lists of original herbs and corresponding medicinal herbs of similar efficacy. RESULTS: The average area under curve (AUC) of the proposed algorithm was found to be about 500% larger than the random selection method. We found that the proposed algorithm puts more hits at the front of the top-10 list than the random selection method, and precisely discerns the efficacy of the herbs. It was also found that the AUC of the experiments either remained the same or increased slightly in all three validation datasets as the search range was increased. CONCLUSION: This study reveals and proves that the proposed algorithm is significantly more accurate and efficient in finding alternative herbs of similar efficacy than the random selection method. As such, it is hoped that this approach will be used in diverse applications in the ethno-pharmacology field. PMID- 26875629 TI - Clinical, biophysical, immunohistochemical, and in vivo reflectance confocal microscopy evaluation of the response of subjects with sensitive skin to home-use fractional non-ablative photothermolysis device. AB - BACKGROUND: Fractional photothermolysis using professional devices is a well accepted and a widely used technique for skin rejuvenation. Recently, the technology has also been implemented in devices for home-use. Yet, a subpopulation of consumers exists that reacts excessively to this stimulation and reports "sensitive skin" (SS). OBJECTIVE: The goal of this study was to evaluate the response of subjects with SS and NSS to fractional non-ablative photothermolysis to provide additional insights in the pathophysiology of SS. METHODS: Subjects with SS and non-sensitive skin (NSS), selected using a proprietary questionnaire were stimulated by applying a home-use fractional non ablative photothermolysis device. Self-reported perceptions and objective effects were evaluated after 0.5, 8, 24, and 72 hours by clinical, biophysical and immunohistochemical assessment, and in vivo reflectance confocal microscopy (RCM). RESULTS: Significantly fewer mast cells were found in SS compared to NSS subjects, 0.5 and 72 hours after stimulus based on tryptase staining, and SS subjects report discomfort more frequently. Immunohistochemical biomarkers revealed new insights in the effects of fractional non-ablative photothermolysis, which were supported by RCM: peri- and interlesional epidermal proliferation, and changes in keratinocyte differentiation. CONCLUSION: Previously, we have already reported that SS could be elicited by mechanical and chemical stimuli. Thus, mild yet excessive self-reported perceptions described here supports the hypothesis about existence of generalized skin sensitivity. Furthermore, it supports a view point suggesting involvement of TRPV1 receptors in this phenomenon. While histological evaluation, in line with our previous results points to the role of mast cells in SS, overall, however, fractional non-ablative photothermolysis causes only mild damage, nearly equal in SS and NSS and could be used as an in vivo model for skin regeneration without manipulating the skin barrier. Lasers Surg. Med. 48:474-482, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26875631 TI - Characterization and functional analysis of two inhibitor of apoptosis genes in Zhikong scallop Chlamys farreri. AB - The proteins of inhibitor of apoptosis (IAP) family play important roles in regulation of apoptosis, immunological response and cell proliferation. Here we reported two IAP genes (named CfIAP1 and CfIAP2) in Zhikong scallop Chlamys farreri. The full-length CfIAP1 cDNA contained 1552 nucleotides, encoding a predicted protein of 251 amino acids with two BIR domains. The full-length CfIAP2 cDNA contained 1243 nt, encoding a 356-aa protein with one BIR domain and one RING domain. The two genes are ubiquitously expressed in six types of tissue of C. farreri. The expression levels of CfIAP1 and CfIAP2 were significantly up regulated after challenged with acute viral necrobiotic disease virus, lipopolysaccharide and exposure to air. Subcellular localization assay showed that CfIAP1 was mainly distributed in cytoplasm and CfIAP2 was in cytoplasm and nucleus. As assessed using a kit designed to test Caspase3 function in mammalian cells, the activity of CfCaspase3 was enhanced as a result of the down-regulation of CfIAP2 expression by dsRNA-mediated gene silencing. Our study indicated that CfIAP1 and CfIAP2 may participate in the innate immunity and stress responses and that CfIAP2 might block apoptosis via inhibiting CfCaspase3 indirectly through an unexplored mechanism in C. farreri. PMID- 26875632 TI - The symbiotic role of O-antigen of Burkholderia symbiont in association with host Riptortus pedestris. AB - Riptortus pedestris harboring Burkholderia symbiont is a useful symbiosis model to study the molecular interactions between insects and bacteria. We recently reported that the lipopolysaccharide O-antigen is absent in the Burkholderia symbionts isolated from Riptortus guts. Here, we investigated the symbiotic role of O-antigen comprehensively in the Riptortus-Burkholderia model. Firstly, Burkholderia mutant strains deficient of O-antigen biosynthesis genes were generated and confirmed for their different patterns of the lipopolysaccharide by electrophoretic analysis. The O-antigen-deficient mutant strains initially exhibited a reduction of infectivity, having significantly lower level of symbiont population at the second-instar stage. However, both the wild-type and O antigen mutant symbionts exhibited a similar level of symbiont population from the third-instar stage, indicating that the O-antigen deficiency did not affect the bacterial persistence in the host midgut. Taken together, we showed that the lipopolysaccharide O-antigen of gut symbiont plays an exclusive role in the initial symbiotic association. PMID- 26875633 TI - Identification and involvement of ferritin in the response to pathogen challenge in the abalone, Haliotis diversicolor. AB - Accumulating data has demonstrated that ferritin plays an important role in host defense responses against infection by pathogens in many organisms. In this study, ultracentrifugation was used to isolate ferritin from abalone, Haliotis diversicolor, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) analysis revealed that this ferritin consisted of two subunits (designated as HdFer1 and HdFer2). There are no disulfide bonds between the HdFer1 and HdFer2 subunits; however, these subunits co-assemble to form heteropolymers. A novel ferritin subunit (HdFer2) was cloned from H. diversicolor by 5' and 3' RACE (rapid amplification of cDNA ends) approach. The full-length HdFer2 cDNA sequence consists of 878 bp with an open reading frame of 513 bp that encodes a protein that is 170 amino acids in length. Quantitative real-time PCR analysis revealed that HdFer1 and HdFer2 were transcribed in various tissues, such as the mantle, gill and hepatopancreas, with the highest levels of expression in the hepatopancreas. Following a challenge with the pathogen, Vibrio harveyi, the expression of HdFer1 and HdFer2 were markedly induced at different times. This study has identified a novel ferritin subunit in H. diversicolor which will contribute to further exploration of the role of ferritin in mollusk innate immune defense against invading pathogens. PMID- 26875634 TI - Neuropeptide Y is an angiogenic factor in cardiovascular regeneration. AB - In diabetic cardiomyopathy, there is altered angiogenic signaling and increased oxidative stress. As a result, anti-angiogenic and pro-inflammatory pathways are activated. These disrupt cellular metabolism and cause fibrosis and apoptosis, leading to pathological remodeling. The autonomic nervous system and neurotransmitters play an important role in angiogenesis. Therapies that promote angiogenesis may be able to relieve the pathology in these disease states. Neuropeptide Y (NPY) is the most abundantly produced and expressed neuropeptide in the central and peripheral nervous systems in mammals and plays an important role in promoting angiogenesis and cardiomyocyte remodeling. It produces effects through G-protein-coupled Y receptors that are widely distributed and also present on the myocardium. Some of these receptors are also involved in diseased states of the heart. NPY has been implicated as a potent growth factor, causing cell proliferation in multiple systems while the NPY3-36 fragment is selective in stimulating angiogenesis and cardiomyocyte remodeling. Current research is focusing on developing a drug delivery mechanism for NPY to prolong therapy without having significant systemic consequences. This could be a promising innovation in the treatment of diabetic cardiomyopathy and ischemic heart disease. PMID- 26875635 TI - Nerol alleviates pathologic markers in the oxazolone-induced colitis model. AB - Nerol is a natural monoterpene with antinociceptive and anti-inflammatory properties. Its possible beneficial effects in ulcerative colitis and its corresponding mechanism of action have not been determined to date. The aim of this study was to investigate whether nerol prevents the appearance of pathological markers and hyperalgesia in oxazolone-induced colitis, and protects against gastric damage produced by ethanol. The experimental design included groups of oxazolone-treated mice receiving nerol at 10-300 mg/kg, p.o., or a reference drug (sulfasalazine, 100 mg/kg, p.o.) compared to sham and untreated groups. Gastric damage was evaluated in the absolute ethanol-induced ulcer model in rats. Variables measured in animals with oxazolone-induced colitis included weight loss, stool consistency and macroscopic colon damage; mechanical nociception was determined by the use of von Frey filaments, whereas levels of inflammatory cytokines were assessed by enzyme-linked immunosorbent assay. Nerol (30-300 mg/kg, p.o.) prevented or significantly decreased the pathological alterations observed in the oxazolone- induced colitis model. It also showed antinociceptive effects and reduced the increased levels of inflammatory cytokines (IL-13 and TNF-alpha). Gastric damage was also prevented starting at 10 mg/kg, p.o. In conclusion, our results provide evidence for a beneficial effect of nerol after colitis induction involving tissue protection, antinociception and modulation of the immunological system, suggesting the therapeutic potential of this monoterpene as a novel alternative in controlling ulcerative colitis. PMID- 26875636 TI - Antihyperuricemic effects of thiadiazolopyrimidin-5-one analogues in oxonate treated rats. AB - Hyperuricemia is a risk factor for not only gout, but also to a variety of disorders that affect the vital organ systems of the human body. The xanthine oxidase (XO) is the key enzyme in the production of uric acid and its inhibition can inhibit hyperuricemia. Although, XO inhibitor allopurinol is widely prescribed antigout agent but its use is not without any side effects. Previously, we described the synthesis of four novel thiadiazolopyrimidin-5-one analogues as effective XO inhibitors and molecular docking studies also confirmed this. When these analogues were tested in potassium oxonate treated rats, their serum uric acid and creatinine levels were dropped significantly from 4.85+/-0.03 mg/dl to 1.21+/-0.01 mg/dl and 0.92+/-0.02 mg/dl to 0.40+/-0.02 mg/dl respectively. Among the pyrimidine analogues tested, 6a was most potent. Histological examinations of both liver and kidney tissues exhibited severe necrosis in oxonate treated rats and pyrimidine analogues could significantly attenuate this with a correlative inhibitory profile of hepatic XO from the same rats. Our results demonstrate antihyperuricemic effect of novel thiadiazolopyrimidin-5-one analogues in oxonate treated rats, which can be further explored not only as antigout therapeutics but also in other systems where hyperuricemia is the driving cause of the disease. PMID- 26875637 TI - Orientin protects myocardial cells against hypoxia-reoxygenation injury through induction of autophagy. AB - Orientin, a flavonoid exists in Chinese traditional herbal Polygonum orientale L., has been previously demonstrated to protect against myocardial ischemia reperfusion injury (MIRI) through inhibition of apoptosis. However, the underlying mechanisms remain to be elucidated and we therefore in this study investigated the effects of orientin on autophagy during MIRI in rats. The results indicate that orientin, at the concentrations of 10 and 30 MUM in the cultures of neonatal rat cardiomyocytes, promoted the induction of autophagy, increasing the formation of autophagosomes and enhancing the expression of LC3 puncta, LC3-II/LC3-I ratio and Beclin 1 after hypoxia/reoxygenation. The induction of autophagy by orientin correlated with enhanced cell viability and decreased apoptosis, which was significantly attenuated by autophagy inhibitor wortmannin, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Moreover, application of orientin increased the activation of AMPK and Akt, downregulated the phosphorylation of mammalian target of rapamycin (mTOR) and the expression of Raptor, and enhanced the interaction between Beclin 1 and Bcl-2 in endoplasmic reticulum due to increased phosphorylation of Beclin 1 and decreased phosphorylation of Bcl-2. Our investigation suggests that the cardioprotective effects of orientin during MIRI may be mediated through the balance of autophagy through regulating AMPK, Akt, mTOR, and Bcl-2 associated signaling pathways. PMID- 26875638 TI - Stable gastric pentadecapeptide BPC 157 heals rat colovesical fistula. AB - To establish the effects of BPC 157 on the healing of rat colovesical fistulas, Wistar Albino male rats were randomly assigned to different groups. BPC 157, a stable gastric pentadecapeptide, has been used in clinical applications specifically, in ulcerative colitis-and was successful in treating both external and internal fistulas. BPC 157 was provided daily, perorally, in drinking water (10ug/kg, 12ml/rat/day) until sacrifice or, alternatively, 10ug/kg or 10ng/kg intraperitoneally, with the first application at 30min after surgery and the last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). Assessment (i.e., colon and vesical defects, fistula leaking, fecaluria and defecation through the fistula, adhesions and intestinal obstruction as healing processes) took place on days 7, 14 and 28. Control colovesical fistulas regularly exhibited poor healing, with both of the defects persisting; continuous fistula leakage; fecaluria and defecation through the fistula; advanced adhesion formation; and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally and in ug- and ng-regimens rapidly improved the whole presentation, with both colon and vesical defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised until it reached the values of healthy rats, there were no signs of fecaluria and no defecation through the fistula, there was counteraction of advanced adhesion formation or there was an intestinal obstruction. In conclusion, BPC 157 effects appear to be suited to inducing full healing of colocutaneous fistulas in rats. PMID- 26875639 TI - E3 ubiquitin ligases as novel targets for inflammatory diseases. AB - Ubiquitination is one of the post translational modifications which decide the fate of various proteins in the cells, by either directing them towards proteasomal degradation or participation in several cell signalling pathways. Recently, the role of ubiquitination has been unravelled in pathogenesis and progression of various diseases, where inflammation is critical, like obesity, insulin resistance, atherosclerosis, angiotensin-II induced cardiac inflammation and asthma. E3 ligases are known to be instrumental in regulation of the inflammatory cascade. This review focuses on the role of different E3 ligases in the development of inflammatory diseases and thus may help us to target these E3 ligases in future drug discovery to prevent inflammation. PMID- 26875640 TI - Nigella sativa (black seed) effects on plasma lipid concentrations in humans: A systematic review and meta-analysis of randomized placebo-controlled trials. AB - The effects of Nigella sativa (NS) on plasma lipid concentrations are controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. PubMed Medline, SCOPUS, Web of Science, and Google Scholar databases were searched (up to August 2015) to identify RCTs investigating the impact of NS on total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and triglycerides concentrations. A random-effects model and the generic inverse variance weighting method were used for quantitative data synthesis. Meta-regression, sensitivity analysis, and publication bias assessments were performed using standard methods. A total of 17 RCTs examining the effects of NS on plasma lipid concentrations were included. Meta-analysis suggested a significant association between NS supplementation and a reduction in total cholesterol (weighed-mean-difference [WMD]: -15.65mg/dL, 95% CI: -24.67, -6.63, p=0.001), LDL-C (WMD: -14.10mg/dL, 95% CI: -19.32, -8.88, p<0.001), and triglyceride levels (WMD: -20.64mg/dL, 95% CI: 30.29, -11.00, p<0.001). No significant effect on HDL-C concentrations (WMD: 0.28mg/dL, 95% CI: -1.96, 2.53, p=0.804) was found. A greater effect of NS seed oil versus seed powder was observed on serum total cholesterol and LDL-C levels, and an increase in HDL-C levels was found only after NS seed powder supplementation. NS has a significant impact on plasma lipid concentrations, leading to lower total cholesterol, LDL-C, and TG levels while increased HDL-C is associated with NS powder only. Further RCTs are needed to explore the NS benefits on cardiovascular outcomes. PMID- 26875641 TI - Influence of enrofloxacin traces in drinking water to doxycycline tissue pharmacokinetics in healthy and infected by Mycoplasma gallisepticum broiler chickens. AB - Most of antibiotics, administrated in the treatment of poultry diseases are dissolved in drinking water, and it can lead to water supply systems contamination, especially when the regular cleaning is not using. This situation can lead to unconscious administration of low doses of antibiotics to untreated animals. The aim of this study was to clarify the impact of the exposure of enrofloxacin traces (500 MUg l(-1)) to doxycycline pharmacokinetics in healthy and experimentally Mycoplasma gallisepticum infected broiler chickens., Two experimental groups, received of enrofloxacin in water and all groups, received 20 mg kg(-1) bw of doxycycline. The compounds concentrations in muscles and livers were determined by LC-MS/MS. The maximum drug tissue concentration (Cmax) of doxycycline was highest in liver obtained from infected chickens which, received enrofloxacin traces (ENR + DC/MG). It was about 40% higher than in healthy chickens from group I which received only doxycycline. It was found that the concentration-time curve AUC(0-t) values in group ENR + DC/MG were almost 75% higher than in the group (DC) and 35% higher than in group (ENR + DC) which also received enrofloxacin traces. The constant exposure of broiler chickens on enrofloxacin traces as well as infection, may significantly influenced on doxycycline tissue pharmacokinetic profile. PMID- 26875642 TI - Assessment of the inhibition potential of Licochalcone A against human UDP glucuronosyltransferases. AB - Licochalcone A (LCA) is a major bioactive compound in Licorice, a widely used herbal medicine. In this study, the inhibitory effects of LCA against human UDP glucuronosyltransferases (UGTs) and LCA associated herb-drug interactions were systematically investigated. Our results demonstrated that LCA displayed broad spectrum inhibition against human UGTs. LCA exhibited strong inhibitory effects against UGT1A1, 1A3, 1A4, 1A6, 1A7, 1A9, and 2B7 (both IC50 and Ki values lower than 5 MUM), while showing moderate inhibitory effects against UGT1A8, 1A10, 2B4, 2B15, and 2B17. The inhibitory effects of LCA against two major UGTs, including UGT1A1 and 1A9, were further investigated in human liver microsomes (HLMs), where the potential risks of LCA via inhibition of UGT1A1 and 1A9 were predicted by combining the in vitro inhibitory data and physiological data. The results from this study also showed that several LCA-containing products were able to increase the area under the curve (AUC) of the substrates that were predominantly metabolized by UGT1A1 or 1A9. These findings together demonstrate that LCA has a potent and broad-spectrum inhibitory effect against most human UGTs and thus suggest that much caution should be exercised when high-dose LCA is co administered with UGT substrates. PMID- 26875643 TI - Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. MATERIALS AND METHODS: Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. RESULTS: CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. CONCLUSION: MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. PMID- 26875645 TI - Current therapeutic role and medicinal potential of Scutellaria barbata in Traditional Chinese Medicine and Western research. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria barbata is a common herb in Traditional Chinese Medicine (TCM) most often used to treat cancer. S. barbata has been found to exhibit efficacy both in vitro and in vivo on a variety of cancer types. Similarly encouraging results have been shown in patients with metastatic breast cancer from Phase Ia and Ib clinical trials. This study aims to elucidate the current use of S. barbata by TCM practitioners and in current Western research. MATERIALS AND METHODS: Semi-structured interviews were conducted with fifteen TCM practitioners in Beijing and Nanjing, China to understand their clinical use of S. barbata. Practitioners were also asked to comment on the future development of TCM using Western research methods and the potential for integration of the two types of medicine in clinical therapy. Statistical analyses were conducted to compare use of S. barbata by disease and in conjunction with other herbs. RESULTS: Current Western research related to S. barbata is focused on cancer treatment, which corresponds to the most common use of S. barbata by TCM practitioners. Other common uses that practitioners reported included infection and inflammation, for which Beijing practitioners reported use of S. barbata more often than Nanjing practitioners (p<0.05). Hedyotis diffusa was found to be the most commonly cited herb to pair with S. barbata for cancer treatment (p<0.05). When compared to Western clinical trials of BZL101, an S. barbata extract, TCM practitioners reported using smaller doses of S. barbata in shorter durations, in combination with numerous other herbs with the goal to potentiate therapeutic efficacy and mitigate side effects. In addition, TCM practitioners repeatedly emphasized symptom differentiating as the key to achieving maximum therapeutic potential of S. barbata, a factor typically overlooked in Western research. CONCLUSION: Similarities and differences in diagnosis and treatment regimens between TCM practitioners and Western research have the potential to shed light on possible new avenues of research. Additional research may prove beneficial on possible synergistic effects of herbs commonly used with S. barbata, such as Hedyotis diffusa and Lobelia chinensis. PMID- 26875644 TI - Pharmacological characteristics of Artemisia vulgaris L. in isolated porcine basilar artery. AB - ETHNOPHARMACOLOGICAL RELEVANCE: In Vietnamese traditional herbalism, there are conflicting opinions about the effect of Artemisia vulgaris L. (AVL, English name: mugwort) on hypertension. Some ethnic doctors recommend the use of AVL for treatment of hypertension, whereas others advise against it. The purpose of this study was to clarify the pharmacological characteristics of AVL in isolated arteries to explain the conflicts surrounding the use of AVL for treatment of hypertension. MATERIALS AND METHODS: We initially performed a functional study using an organ bath system to investigate the effect of AVL extract on isolated porcine basilar artery. We then measured the change in intracellular free Ca(2+) concentration elicited by AVL using cultured smooth muscle cells loaded with the Ca(2+) indicator fluo-4. Finally, using HPLC, we determined the active components in AVL. RESULTS AND DISCUSSION: AVL induced vasoconstriction at resting tension, and endothelial removal enhanced this effect significantly. Pretreatment with PD123319 (an AT2 receptor antagonist), Nomega-nitro-L-arginine (a nitric oxide synthase inhibitor), or both, also enhanced this effect. AVL-induced contraction was competitively inhibited by methiothepin (a 5-HT1 and 5-HT2 receptor antagonist) in the presence of ketanserin (a 5-HT2 receptor antagonist). Removal of extracellular calcium with nifedipine (an L-type Ca(2+) channel blocker) or ruthenium red (a ryanodine receptor blocker) significantly reduced AVL-induced contraction, whereas losartan (an AT1 receptor antagonist) and diphenhydramine (a H1 receptor antagonist) had no effect on this contraction. AVL increased the intracellular free Ca(2+) concentration in cultured cells, and this increment was inhibited by methiothepin. HPLC analysis revealed that the retention time of the first peak in the AVL profile was similar to that of the 5-HT standard, and that addition of 5-HT to the AVL sample enhanced this peak. On the other hand, AVL induced endothelium-independent relaxation under precontracted conditions with 60mM KCl. Captopril (an angiotensin converting enzyme inhibitor), atenolol (a beta1 receptor antagonist) and cimetidine (a H2 receptor antagonist) had no effect on this relaxation. In Ca(2+)-free 60mM KCl-containing solution, pretreatment with AVL significantly inhibited CaCl2-induced contraction. CONCLUSION: For the first time, the present study has demonstrated that AVL has two opposite effects, contraction and relaxation, on isolated artery, which may help to explain the conflicting indications for AVL in traditional herbalism. 5 HT is a significant factor affecting artery contraction in the presence of AVL. PMID- 26875646 TI - Antibacterial constituents of Eremophila alternifolia: An Australian aboriginal traditional medicinal plant. AB - ETHNOPHARMACOLOGICAL RELEVANCE: For traditional medicinal purposes Aboriginal Australians have utilised numerous plant species, Eremophila alternifolia is among the most prominent. Traditionally, fresh leaves, leaf-infusions and handmade leaf-pastes have been used as both external and internal preparations to provide relief from a variety of conditions. Preparations of the species have been used to treat various infections of skin, eyes and throat including the treatment of septic wounds. These usages suggest that the plant contains antibacterial compounds; however, to date they have not been isolated and identified. AIM OF THE STUDY: The present study aimed to identify antibacterial compounds from this important traditionally recorded medicinal species. MATERIALS AND METHODS: Bioassay-guided fractionation was used to isolate compounds from the crude leaf-extract. Antibacterial activity of pure compounds was assessed through broth microdilution method by determining both minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Structure elucidation was performed using spectroscopic techniques such as 1D and 2D nuclear magnetic resonance spectroscopy and high resolution mass spectrometry. RESULTS: Four compounds have been isolated from the leaf-extract; they include previously known flavanones [pinobanksin (1), pinobanksin-3-acetate (2) and pinobanksin-3 cinnamate (3)] and a serrulatane diterpene, 8-hydroxyserrulat-14-en-19-oic acid (4). While compound 4 had been found in other Eremophilas, flavanones 2 and 3 are identified for the first time from the genus Eremophila. The flavanone 3 is the most promising antibacterial compound with significant activity (10-20uM) against strains of the Gram-positive bacterium Staphylococcus aureus including methicillin resistant and biofilm forming strains. No activity was observed for any isolated compounds against the Gram-negative bacterium Escherichia coli. CONCLUSION: The antibacterial activity of the crude extract of E. alternifolia and of the isolated compounds against Gram-positive bacteria provides a Western scientific explanation of the therapeutic modality of this plant species in traditional Aboriginal medicinal practice. PMID- 26875647 TI - Antimycobacterial and cytotoxic activity of selected medicinal plant extracts. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. MATERIAL AND METHODS: The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96(r) AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2 (4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. RESULTS: Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3ug/mL against M. tuberculosis; Strain H37Ra (ATCC(r) 25,177TM) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). CONCLUSION: The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. PMID- 26875648 TI - 1-Year Outcomes of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus Eluting Stents: A Propensity-Matched Comparison of the GHOST-EU and XIENCE V USA Registries. AB - OBJECTIVES: The purpose of this study was to compare the 1-year outcomes of the ABSORB everolimus-eluting bioresorbable scaffold (BRS) (Abbott Vascular, Santa Clara, California) and the XIENCE everolimus-eluting stent (EES) (Abbott Vascular) in patients undergoing percutaneous coronary intervention. BACKGROUND: Randomized studies of the ABSORB BRS have been performed in selected patient and lesion scenarios. The available registries of the ABSORB BRS reflect real-world practice more closely compared with randomized studies, but most of them are limited by the small sample size and the lack of comparative outcomes versus second-generation drug-eluting stents. METHODS: A total of 1,189 consecutive patients treated with ABSORB BRS from the GHOST-EU (Gauging coronary Healing with bioresorbable Scaffolding plaTforms in EUrope) registry and 5,034 patients treated with XIENCE EES from the XIENCE V USA registry were analyzed. Clinical outcomes were compared with the use of propensity-score matching techniques and reported as Kaplan-Meier estimates and absolute risk difference (D) with 95% confidence intervals (CIs). The primary endpoint was a device-oriented composite endpoint, including cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization at 1-year follow-up. RESULTS: After propensity score matching was performed for the entire population (N = 6,223), there were 905 matched pairs of patients. In the matched cohort (N = 1,810), there was no significant difference between ABSORB BRS and XIENCE EES in the risk of device-oriented composite endpoint at 1 year (5.8% vs. 7.6%, D = -1.8 [95% CI: -4.1 to 0.5]; p = 0.12). Cardiac death was less likely to occur in the ABSORB BRS group (0.7% vs. 1.9%, D = -1.2 [95% CI: -2.2 to 0.2]; p = 0.03), and a trend toward a reduction in myocardial infarction was noted with ABSORB BRS compared with XIENCE EES (2.4% vs. 4.0%, D = -1.6 [95% CI: -3.2 to 0.0]; p = 0.07). Conversely, no differences in ischemia-driven target lesion revascularization (4.6% vs. 3.5%, D = 1.1 [95% CI: -0.7 to 2.9]; p = 0.22) and definite or probable device thrombosis (1.8% vs. 1.1%, D = 0.7 [95% CI: -0.4 to 1.8]; p = 0.23) were detected between ABSORB BRS and XIENCE EES. CONCLUSIONS: In a contemporary large cohort of patients undergoing percutaneous coronary intervention with ABSORB BRS, the combined rate of ischemic events at 1 year was low and nonsignificantly different compared with matched patients treated with XIENCE EES. PMID- 26875649 TI - Assessment of the Radiation Exposure of Surgeons and Patients During a Lumbar Microdiskectomy and a Cervical Microdiskectomy: A French Prospective Multicenter Study. AB - OBJECTIVE: Cervical and lumbar disk herniations are the most frequently carried out procedures in spinal surgery. Often, a few snapshots during the procedure are necessary to validate the level or to position the implant. The objective of this study is to quantitatively estimate the radiation received by a spine surgeon and patient during a low-dose radiation procedure. METHODS: We conducted a prospective multicenter study in France from November 2014 to April 2015. Four spine centers were monitored for radiation received by surgeons during interventions for lumbar disk herniation and cervical disk herniation. RESULTS: A total of 134 patients were included. For lumbar disk herniation, the average exposure for the surgeon was 0.584 MUSv on the chest, 5.291 MUSv on the lens, and 9.295 MUSv on the hands per procedure. For these procedures, the dose area product (DAP) was 94.2 +/- 198.4 cGy.cm(2), and the fluoroscopic time was 10.2 +/ 16.9 seconds. For a herniated cervical disk, the average exposure for the surgeon was 0.122 MUSv on the chest, 3.106 MUSv on the lens, and 7.143 MUSv on the hands per procedure. For these procedures, the DAP was 35.7 +/- 72.1 cGy.cm(2), and the fluoroscopic time was 19.7 +/- 13.7 seconds. CONCLUSIONS: Exposure to x-rays for surgeons and patients during surgery for lumbar disk herniation is higher than during surgery for cervical herniation disk. Our results show that radiation exposure to the spine surgeon is still far below the annual dose limits. PMID- 26875650 TI - Use of Intramedullary K-Wire to Enhance Fibular Graft Placement in 4-Level Thoracolumbar Corpectomy for Pott Disease: Case Report and Review of Literature. AB - BACKGROUND: Reports of tuberculosis involving >=4 contiguous spinal levels are rare. Surgery is often required in this population for neurological decompression and stabilization. These patients appear to be particularly predisposed to complications that include incomplete recovery of neurological function after decompression as well as post-treatment kyphosis. In settings with limited available instrumentation, reconstruction of the anterior column can be challenging. CASE DESCRIPTION: A 35-year-old woman presented with back pain, progressive weakness in her bilateral lower extremities, and inability to walk for 2 months. Imaging demonstrated anterior destruction of T10, T11, T12, and L1 with severe retropulsion and cord impingement at T11-T12. The patient was taken for anterolateral corpectomies of T10-L1 with decompression of the thoracic spinal cord and fibular strut autograft placement followed by a T8 to L3 posterior spinal fusion. An intramedullary Kirschner-wire (K-wire) was placed during the anterolateral procedure to enhance fibular graft placement and prevent dislodgement before definitive posterior fusion. CONCLUSIONS: At follow-up five and-a-half months after the operation, the patient had recovered full strength and was ambulating without difficulty. Imaging at this time demonstrated stable restoration of alignment without graft dislodgement. Intramedullary fibular K wire placement in this procedure helped to optimize anterior column reconstruction. The principles used in this report may prove beneficial to surgeons in developing countries who encounter pathology of this extent. PMID- 26875651 TI - Anatomical Origin of Tuberculum Sellae Meningioma: Off-Midline Location and Its Clinical Implications. AB - OBJECTIVE: Tuberculum sellae meningiomas (TSM) arise from the dura mater of tuberculum sellae, limbus sphenoidale, and chiasmatic sulcus and cause asymmetric visual disturbances. In this study, we analyzed the laterality of the origin of TSM and discussed its clinical implications on immediate and long-term visual outcomes. METHODS: Between 1994 and 2013, TSM was diagnosed in 100 patients after microsurgical resection. The medical records, radiologic features, and operative findings were retrospectively reviewed and analyzed in these patients. RESULTS: Visual disturbances were evident in 95 patients (95%) after neuro-ophthalmologic testing. Among them, 89 patients (89%) showed marked asymmetric visual field defect, and 6 patients (6%) had relatively symmetric visual field defect. On intraoperative inspection, the origin of TSM was at the one lateral end portion of the tuberculum sellae in 85 patients (85%). In 15 patients (15%), the TSM originated from the midline region, including the central portion of the tuberculum sellae (n = 13) and diaphragm sellae (n = 2). Optic canal involvement was observed in 73 patients (73%). Preexisting visual field defects were improved in 70 patients (70%), were stationary in 25 patients (25%), and aggravated in 5 patients (5%) during postoperative follow-up (mean 58 months, 24~122 months). The preoperative symptom duration, the laterality of the origin of TSM, and optic disc atrophy were associated with long-term poor visual outcomes. CONCLUSIONS: Most TSMs that originated from the dura of one lateral end portion of the tuberculum sellae correlated with asymmetric visual symptoms and poor visual outcomes. This microsurgical feature should be considered in the planning of optimal surgical strategy to achieve favorable outcomes. PMID- 26875652 TI - Cost Analysis of Spinal Versus General Anesthesia for Lumbar Diskectomy and Laminectomy Spine Surgery. AB - BACKGROUND: Lumbar spine surgery can be performed using various anesthetic modalities, most notably general or spinal anesthesia. Because data comparing the cost of these anesthetic modalities in spine surgery are scarce, this study asks whether spinal anesthesia is less costly than general anesthesia. METHODS: A total of 542 patients who underwent elective lumbar diskectomy or laminectomy spine surgery between 2007 and 2011 were retrospectively identified, with 364 having received spinal anesthesia and 178 having received general anesthesia. Mean direct operating cost, indirect cost (general support staff, insurance, taxes, floor space, facility, and administrative costs), and total cost were compared among patients who received general and spinal anesthesia. Linear multiple regression analysis was used to identify the effect of anesthesia type on cost and determine the factors underlying this effect, while controlling for patient and procedure characteristics. RESULTS: When controlling for patient and procedure characteristics, use of spinal anesthesia was associated with a 41.1% lower direct operating cost (-$3629 +/- $343, P < 0.001), 36.6% lower indirect cost (-$1603 +/- $168, P < 0.001), and 39.6% lower total cost (-$5232 +/- $482, P < 0.001) compared with general anesthesia. Shorter hospital stay, shorter duration of anesthesia, shorter duration of operation, and lower estimated blood loss contributed to lower costs for spinal anesthesia, but other factors beyond these were also responsible for lower direct operating and total costs. CONCLUSIONS: When comparing the benefits of spinal and general anesthesia, spinal anesthesia is less costly when used in patients undergoing lumbar diskectomy and laminectomy spine surgery. PMID- 26875653 TI - Advantage of Extended Craniofacial Resection for Advanced Malignant Tumors of the Nasal Cavity and Paranasal Sinuses: Long-Term Outcome and Surgical Management. AB - OBJECTIVE: Craniofacial resection (CFR) for advanced sinonasal malignant tumors (SNMTs) is mandatory for radical resection. Surgeons must be aware of perioperative complications and long-term outcome because this procedure is extremely invasive, especially when the tumor involves the anterior skull base. METHODS: Thirty-eight consecutive surgical patients with advanced SNMT of T4 stage or Kadish stage C (31 men and 7 women; mean age, 55 years; range: 19-76 years) treated with CFR in the past 28 years were followed up for 59.4 months. In cases of unilateral orbital extension, en-bloc resection was achieved using several neurosurgical techniques (extended CFR) from 2005 onwards. Herein, we evaluated the safety and effectiveness of surgery by comparing survival data between 2 time periods (first stage: 1984-2004, second stage: 2005-2012). RESULTS: Squamous cell carcinoma was the most common histological type observed (65.8%), followed by esthesioneuroblastoma (15.8%). Using a combination of adjuvant radiation therapy, the 5-year overall survival and the 5-year disease specific survival rates were 55.5% and 59.4%, respectively. Sarcomatous histology was a poor prognostic factor. The 5-year disease-specific survival rate was 48.9% in the first stage and improved to 82.1% in the second stage (P = 0.057); this was related to improvements in local control rate. CONCLUSIONS: CFR and postoperative radiotherapy are safe and effective for treating advanced SNMTs. Extended CFR, including radical orbital exenteration, may contribute to good long term outcomes. A diverse surgical team may help perform radical resection and reconstruction in patients with advanced tumors. PMID- 26875654 TI - "Inverted Gull Wing" Dural Closure and Middle Fossa Floor Reconstruction After Transzygomatic Infratemporal Fossa Approach. AB - BACKGROUND: Ineffective closure of complex skull base approaches leads to wound complications and cerebrospinal fluid (CSF) leak. This can result in protracted hospital stays, additional procedures, delayed postoperative recovery, and increased cost of care. Removal of large middle fossa-infratemporal fossa tumors are particularly problematic as they result in a large dead space with gravity facilitated CSF leakage into the cavity. In this report we describe the use of a novel technique, the "inverted gull wing" titanium mesh reconstruction. METHODS: Attempts to address this problem have focused primarily on closure and the use of myocutaneous flaps. Patients who have had multiple prior treatments are often afflicted with significant tissue attenuation that preclude dural closure or the use of local flaps. Although vascularized free flaps are an effective option in this scenario, they can add significant operative time and often yield suboptimal cosmetic results. We describe the use of the inverted gull wing titanium mesh reconstruction in the closure of 2 patients who underwent complex transzygomatic infratemporal fossa approaches for tumor with dural and sinonasal transgression. RESULTS: Postoperatively, there were no pseudomeningoceles, CSF leaks, or technique-related morbidities. CONCLUSIONS: The inverted gull wing technique represents a simple, fast, and effective closure for complex transzygomatic infratemporal fossa approaches. PMID- 26875655 TI - Historical Risk Factors Associated with Seizure Outcome After Surgery for Drug Resistant Mesial Temporal Lobe Epilepsy. AB - OBJECTIVE: To investigate the possible influence of risk factors on seizure outcome after surgery for drug-resistant temporal lobe epilepsy (TLE) and mesial temporal sclerosis (MTS). METHODS: This retrospective study recruited patients with drug-resistant MTS-TLE who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center and were followed for a minimum of 1 year. Patients had been prospectively registered in a database from 1986 through 2014. After surgery outcome was classified into 2 groups: seizure-free or relapsed. The possible risk factors influencing long-term outcome after surgery were investigated. RESULTS: A total of 275 patients with MTS-TLE were studied. Two thirds of the patients had Engel's class 1 outcome and 48.4% of the patients had sustained seizure freedom, with no seizures since surgery. Patients with a history of tonic-clonic seizures in the year preceding surgery were more likely to experience seizure recurrence (odds ratio, 2.4; 95% confidence interval 1.19 4.80; P = 0.01). Gender, race, family history of epilepsy, history of febrile seizure, history of status epilepticus, duration of disease before surgery, intelligence quotient, and seizure frequency were not predictors of outcome. CONCLUSIONS: Many patients with drug-resistant MTS-TLE respond favorably to surgery. It is critical to distinguish among different types and etiologies of TLE when predicting outcome after surgery. PMID- 26875656 TI - Minimally Invasive Spinal Decompression in Patients Older Than 75 Years of Age: Perioperative Risks, Complications, and Clinical Outcomes Compared with Patients Younger Than 45 Years of Age. AB - OBJECTIVE: Minimally invasive spinal decompression for the treatment of spinal stenosis or disk herniation is often indicated if conservative management fails. However, the influence of old age on the risk of postoperative complications and clinical outcome is not well understood. We therefore sought to compare complication rates and outcomes after minimally invasive surgery decompression and discectomy in elderly patients with a cohort of younger patients undergoing similar procedures. METHODS: We evaluated medical records of 61 patients older than 75 years and 69 patients younger than 45 years that underwent minimally invasive lumbar decompression between April 2009 and July 2013 at our institute. Medical history, American Society of Anesthesiologists score, perioperative mortality, complications, and revision surgery rates were analyzed. Patient outcomes included visual analog scale and EuroQol-5 Dimension scores. RESULTS: The average age was 78.66 +/- 4.42 years in the elderly group and 33.59 +/- 6.7 years in the younger group. No major postoperative complications were recorded in either group, and all recruited patients were still alive at the time of the last follow-up. No statistically significant difference existed in the surgical revision rate between the groups. Both groups showed significant improvement in their outcome scores after surgery. CONCLUSIONS: Our results indicate that minimally invasive decompressive surgery is a safe and effective treatment for elderly patients and does not pose an increased risk of complications. Future prospective studies are necessary to validate the specific advantages of the minimally invasive techniques in the elderly population. PMID- 26875657 TI - The Microsurgical Anatomy of the Orbitofrontal Arteries. AB - OBJECTIVE: The orbitofrontal (or frontobasal) arteries (OFAs) are the medial (MOFA) and lateral (LOFA) orbitofrontal artery, branches of the anterior and middle cerebral artery, respectively. They supply the orbitofrontal cortex. The purpose of this microscopic cadaveric study was the detailed and precise anatomic identification of the OFAs along their course. METHODS: Twenty formalin-fixed, colored latex-injected cadaveric heads were studied with the aid of an operating microscope and microsurgical instrumentation. The anatomy of the OFAs was examined after removing the cerebrum from the cranial vault. Anatomic features of the MOFA and LOFA were investigated and assessed in relation to demographic and anthropometric variables. RESULTS: The MOFA supplies approximately 15 branches and LOFA almost 16 branches. The MOFA provides 1 branch to the olfactory bulb and 4 branches to the olfactory tract, and there are approximately 2 MOFA-LOFA anastomoses per hemisphere (novel finding). The MOFA origin is located approximately 7.9 mm anterior to the anterior communicating artery and 4.7 cm posterior to the anterior limit of the gyrus rectus. The LOFA origin is located approximately 11.1 mm from the middle cerebral artery bifurcation. Younger, shorter, and lighter individuals have more MOFA-LOFA anastomoses. Finally, the number of MOFA branches for the olfactory bulb is positively correlated with the number of MOFA branches for the olfactory tract, as well as with the number of MOFA-LOFA anastomoses. CONCLUSIONS: The present study provides a detailed description of the OFAs' microsurgical anatomy and can help neurosurgeons to easily identify, manipulate, and preserve these vessels during surgery. PMID- 26875658 TI - Endovascular Mechanical Thrombectomy with the Solitaire Device for the Treatment of Acute Basilar Artery Occlusion. AB - OBJECTIVE: To determine the safety and efficacy of endovascular treatment with the Solitaire device for acute basilar artery occlusion (ABAO) and identify factors affecting clinical outcomes. METHODS: We enrolled 36 consecutive ABAO patients (aged 58.6 +/- 8.10 years) who underwent mechanical thrombectomy with the Solitaire device. We analyzed baseline characteristics, mechanical thrombectomy results, and factors predicting clinical outcomes, which were assessed at 90 days. RESULTS: The median prethrombectomy National Institutes of Health Stroke Scale (NIHSS) score was 25.50 (interquartile range: 21.00-29.00); the median prethrombectomy Glasgow Coma Scale (GCS) score was 8.00 (5.00-9.75). Thirty patients (83.3%) had atherosclerotic stenosis of the occluded artery, and 25 underwent angioplasty (69.4%). Recanalization was successful (Thrombolysis in Cerebral Infarction grade: 2b-3) in 34 patients (94.4%). Six symptomatic intracranial hemorrhages (16.67%) occurred. Favorable outcomes (modified Rankin scale [mRS] score: 0-2) were achieved in 27.8% patients (10/36). The overall mortality rate was 30.6% (11/36) at 90 days. On univariate analysis, low prethrombectomy GCS and high post-thrombectomy NIHSS scores were associated with poor outcomes (mRS score >2) and mortality. Prethrombectomy unconsciousness, onset-to-recanalization time > 10.5 hours, and severe stenosis were associated with poor outcomes. Age >= 60 years was associated with mortality. CONCLUSIONS: Endovascular treatment with the Solitaire device yielded high recanalization rates in ABAO patients and favorable clinical outcomes in approximately one third of patients. Intracranial stenosis was the main cause of occlusion. Angioplasty was commonly performed during mechanical thrombectomy to improve recanalization and prognosis. Early recanalization and better prethrombectomy status predicted better outcomes. PMID- 26875660 TI - Risk Factors for the Development of Contralateral Epidural Hematoma Following Decompressive Craniectomy in Patients with Calvarial Skull Fracture Contralateral to the Craniectomy Site. AB - OBJECTIVE: To investigate the frequency and risk factors of contralateral epidural hematoma (CEDH) following decompressive craniectomy (DC) in patients with calvarial skull fracture contralateral to the craniectomy site. METHODS: After reviewing the medical records and radiographs over a 5-year period, 72 patients with calvarial fracture contralateral to the craniectomy site were enrolled to determine the risk factors for the development of CEDH following DC. RESULTS: Among 13 patients with CEDH following DC, all but 1 patient were younger than 60 years of age. In 10 patients (77%) with CEDH, the contralateral calvarial fracture involved more than 1 bone plate. Comparatively, contralateral calvarial fracture involving more than 1 bone plate was noted in 21 patients (35.6%) without CEDH. After multiple logistic regression analysis, only age (P = 0.008, odds ratio [OR] = 0.916, 95% confidence interval [CI] = 0.858-0.987) and number of fracture-involved bone plate (P = 0.006, OR = 10.971, 95% CI = 2.02-59.70) remained independently associated with CEDH development following DC, and CEDH development rate increased by 8.4% with every 1-year decrease in age. CONCLUSIONS: Age and number of fracture-involved bone plate are significant risk factors for CEDH development following DC. Involvement of 2 or more bone plates of contralateral calvarial skull fracture in young adult may prompt an immediate postoperative computed tomography scan to detect the occurrence of CEDH, irrespective of the operative findings and neurologic status. This may prevent devastating neurologic consequences of CEDH and improve therapeutic outcome. PMID- 26875659 TI - In Situ Cranioplasty Technique for Immediate Calvarial Reconstruction to Optimize Cosmesis. AB - OBJECTIVE: One of the goals of calvarial reconstruction after craniectomy is optimization of cosmesis. A simple technique for intraoperative generation of an implant based on the patient's native skull contour for immediate skull reconstruction after craniectomy is described. METHODS: In this technique, a titanium mesh is molded to the contour of the skull in situ and temporarily secured to the calvarium before the craniectomy. After the definitive portion of the procedure, the implant is resecured using the predrilled holes in the skull. RESULTS: In situ titanium cranioplasties are easily contoured to the patient's native skull before, and resecured after, craniectomy. Postoperative cosmesis is excellent. CONCLUSIONS: In selected cases, this technique for in situ cranioplasty before craniectomy generates an implant that mimics the patient's calvarium and results in excellent cosmetic outcomes. PMID- 26875661 TI - Verification of multichannel electrode array integrity by use of cross-channel correlations. AB - BACKGROUND: The use of multichannel electrode arrays (MEAs) presents a number of practical challenges to experimenters including correctly labelling different recording channel locations and identifying sites that may be non-functional or short-circuited. These challenges are likely to increase as the number of sites used in recording increases. NEW METHOD: This paper presents a simple method for assessing MEA integrity based on the observation that physiologically induced signal correlations between nearby channels fall off with distance. Channels that violate this relationship are flagged as being potentially problematic. RESULTS: The method is able to present to the user a list of potentially faulty channels for further inspection. Underlying problems include non-functional, shorted and mislocalised channels and channels carrying spurious noisy signals unrelated to those on other channels. COMPARISON WITH EXISTING METHODS: Computational methods which automatically screen MEAs for faulty electrode channels do not appear to exist in the literature. Currently a user would have to examine single channels, or channel pairs, individually, which would be very time-consuming. CONCLUSIONS: Shorted or mislocalised channels may be more prevalent in MEA recordings than users suspect. The paper presents a simple screening method for identifying such channels prior to carrying out spike-sorting. PMID- 26875662 TI - Reducing premature KCC2 expression rescues seizure susceptibility and spine morphology in atypical febrile seizures. AB - Atypical febrile seizures are considered a risk factor for epilepsy onset and cognitive impairments later in life. Patients with temporal lobe epilepsy and a history of atypical febrile seizures often carry a cortical malformation. This association has led to the hypothesis that the presence of a cortical dysplasia exacerbates febrile seizures in infancy, in turn increasing the risk for neurological sequelae. The mechanisms linking these events are currently poorly understood. Potassium-chloride cotransporter KCC2 affects several aspects of neuronal circuit development and function, by modulating GABAergic transmission and excitatory synapse formation. Recent data suggest that KCC2 downregulation contributes to seizure generation in the epileptic adult brain, but its role in the developing brain is still controversial. In a rodent model of atypical febrile seizures, combining a cortical dysplasia and hyperthermia-induced seizures (LHS rats), we found a premature and sustained increase in KCC2 protein levels, accompanied by a negative shift of the reversal potential of GABA. In parallel, we observed a significant reduction in dendritic spine size and mEPSC amplitude in CA1 pyramidal neurons, accompanied by spatial memory deficits. To investigate whether KCC2 premature overexpression plays a role in seizure susceptibility and synaptic alterations, we reduced KCC2 expression selectively in hippocampal pyramidal neurons by in utero electroporation of shRNA. Remarkably, KCC2 shRNA-electroporated LHS rats show reduced hyperthermia-induced seizure susceptibility, while dendritic spine size deficits were rescued. Our findings demonstrate that KCC2 overexpression in a compromised developing brain increases febrile seizure susceptibility and contribute to dendritic spine alterations. PMID- 26875663 TI - Astrocyte membrane properties are altered in a rat model of developmental cortical malformation but single-cell astrocytic glutamate uptake is robust. AB - Developmental cortical malformations (DCMs) are linked with severe epilepsy and are caused by both genetic and environmental insults. DCMs include several neurological diseases, such as focal cortical dysplasia, polymicrogyria, schizencephaly, and others. Human studies have implicated astrocyte reactivity and dysfunction in the pathophysiology of DCMs, but their specific role is unknown. As astrocytes powerfully regulate glutamate neurotransmission, and glutamate levels are known to be increased in human epileptic foci, understanding the role of astrocytes in the pathological sequelae of DCMs is extremely important. Additionally, recent studies examining astrocyte glutamate uptake in DCMs have reported conflicting results, adding confusion to the field. In this study we utilized the freeze lesion (FL) model of DCM, which is known to induce reactive astrocytosis and cause significant changes in astrocyte morphology, proliferation, and distribution. Using whole-cell patch clamp recording from astrocytes, we recorded both UV-uncaging and synaptically evoked glutamate transporter currents (TCs), widely accepted assays of functional glutamate transport by astrocytes. With this approach, we set out to test the hypothesis that astrocyte membrane properties and glutamate transport were disrupted in this model of DCM. Though we found that the developmental maturation of astrocyte membrane resistance was disrupted by FL, glutamate uptake by individual astrocytes was robust throughout FL development. Interestingly, using an immunolabeling approach, we observed spatial and developmental differences in excitatory amino acid transporter (EAAT) expression in FL cortex. Spatially specific differences in EAAT2 (GLT-1) and EAAT1 (GLAST) expression suggest that the relative contribution of each EAAT to astrocytic glutamate uptake may be altered in FL cortex. Lastly, we carefully analyzed the amplitudes and onset times of both synaptically- and UV uncaging-evoked TCs. We found that in the FL cortex, synaptically-evoked, but not UV uncaging-evoked TCs, were larger in amplitude. Additionally, we found that the amount of electrical stimulation required to evoke a synaptic TC was significantly reduced in the FL cortex. Both of these findings are consistent with increased excitatory input to the FL cortex, but not with changes in how individual astrocytes remove glutamate. Taken together, our results demonstrate that the maturation of astrocyte membrane resistance, local distribution of glutamate transporters, and glutamatergic input to the cortex are altered in the FL model, but that single-cell astrocytic glutamate uptake is robust. PMID- 26875664 TI - Gadd45beta ameliorates L-DOPA-induced dyskinesia in a Parkinson's disease mouse model. AB - The dopamine precursor 3,4-dihydroxyphenyl-l-alanine (L-DOPA) is currently the most efficacious pharmacotherapy for Parkinson's disease (PD). However, long-term L-DOPA treatment leads to the development of abnormal involuntary movements (AIMs) in patients and animal models of PD. Recently, involvement of growth arrest and DNA damage-inducible 45beta (Gadd45beta) was reported in neurological and neurobehavioral dysfunctions. However, little is known about the role of Gadd45beta in the dopaminergic nigrostriatal pathway or L-DOPA-induced dyskinesia (LID). To address this issue, we prepared an animal model of PD using unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra of Gadd45beta(+/+) and Gadd45beta(-/-) mice. Dyskinetic symptoms were triggered by repetitive administration of L-DOPA in these 6-OHDA-lesioned mice. Whereas dopamine denervation in the dorsal striatum decreased Gadd45beta mRNA, chronic L-DOPA treatment significantly increased Gadd45beta mRNA expression in the 6-OHDA lesioned striatum of wild-type mice. Using unilaterally 6-OHDA-lesioned Gadd45beta(+/+) and Gadd45beta(-/-) mice, we found that mice lacking Gadd45beta exhibited long-lasting increases in AIMs following repeated administration of L DOPA. By contrast, adeno-associated virus-mediated expression of Gadd45beta in the striatum reduced AIMs in Gadd45beta knockout mice. The deficiency of Gadd45beta in LID increased expression of DeltaFosB and c-Fos in the lesioned striatum 90 min after the last administration of L-DOPA following 11days of daily L-DOPA treatments. These data suggest that the increased expression of Gadd45beta induced by repeated administration of L-DOPA may be beneficial in patients with PD. PMID- 26875665 TI - Study of the cross-reactivity of fish allergens based on a questionnaire and blood testing. AB - BACKGROUND: Parvalbumin and collagen have been identified as cross-reactive allergens for fish allergies. Although doctors realize that various fish elicit allergies, the targets of food allergen labeling laws were only mackerels and salmons in Japan and mackerels in South Korea. This study aimed to reveal the causative species for fish allergy via questionnaires and blood tests. METHODS: Questionnaire research was conducted in Japan via the internet concerning allergies for fish-allergic patients or their family members. Next, IgE reactivities and cross-reactivities of 26 fish species were analyzed using sera obtained from 16 Japanese patients who were allergic to fish parvalbumin or collagen by enzyme-linked immunosorbent assay (ELISA) and inhibition ELISA. RESULTS: Questionnaire research revealed that 88% patients cannot eat mackerel and salmon in addition to other fish. In addition, 85% respondents were not satisfied with the current food allergen labeling law. In ELISA analyses, we clarified that pooled serum obtained from patients with fish parvalbumin-specific allergies exhibited IgE reactivity to the extracts of most fish species, and pooled serum obtained from patients with fish collagen-specific allergies displayed IgE reactivity to the extracts of all types of fish. Inhibition ELISA experiments revealed cross-reactivities of parvalbumin or collagen to extracts from all fish tested. CONCLUSIONS: Most patients with fish allergies displayed allergic symptoms following the intake of various fish species. In addition, fish parvalbumin and collagen were causative factors of fish allergy and were highly cross-reactive fish panallergens. Therefore, current laws should be revised in Japan and South Korea. PMID- 26875666 TI - Comprehensive profiling of lysine acetylproteome analysis reveals diverse functions of lysine acetylation in common wheat. AB - Lysine acetylation of proteins, a dynamic and reversible post-translational modification, plays a critical regulatory role in both eukaryotes and prokaryotes. Several researches have been carried out on acetylproteome in plants. However, until now, there have been no data on common wheat, the major cereal crop in the world. In this study, we performed a global acetylproteome analysis of common wheat variety (Triticum aestivum L.), Chinese Spring. In total, 416 lysine modification sites were identified on 277 proteins, which are involved in a wide variety of biological processes. Consistent with previous studies, a large proportion of the acetylated proteins are involved in metabolic process. Interestingly, according to the functional enrichment analysis, 26 acetylated proteins are involved in photosynthesis and Calvin cycle, suggesting an important role of lysine acetylation in these processes. Moreover, protein interaction network analysis reveals that diverse interactions are modulated by protein acetylation. These data represent the first report of acetylome in common wheat and serve as an important resource for exploring the physiological role of lysine acetylation in this organism and likely in all plants. PMID- 26875667 TI - Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1. AB - Hypoxia-induced replication stress is one of the most physiologically relevant signals known to activate ATM in tumors. Recently, the ATM interactor (ATMIN) was identified as critical for replication stress-induced activation of ATM in response to aphidicolin and hydroxyurea. This suggests an essential role for ATMIN in ATM regulation during hypoxia, which induces replication stress. However, ATMIN also has a role in base excision repair, a process that has been demonstrated to be repressed and less efficient in hypoxic conditions. Here, we demonstrate that ATMIN is dispensable for ATM activation in hypoxia and in contrast to ATM, does not affect cell survival and radiosensitivity in hypoxia. Instead, we show that in hypoxic conditions ATMIN expression is repressed. Repression of ATMIN in hypoxia is mediated by both p53 and HIF-1alpha in an oxygen dependent manner. The biological consequence of ATMIN repression in hypoxia is decreased expression of the target gene, DYNLL1. An expression signature associated with p53 activity was negatively correlated with DYNLL1 expression in patient samples further supporting the p53 dependent repression of DYNLL1. Together, these data demonstrate multiple mechanisms of ATMIN repression in hypoxia with consequences including impaired BER and down regulation of the ATMIN transcriptional target, DYNLL1. PMID- 26875668 TI - Association between Functional MICA-TM and Behcet's Disease: A Systematic Review and Meta-analysis. AB - The relationships between polymorphisms of the trans-membrane(TM) region located in the major histocompatibility complex (MHC) class I chain-related gene A (MICA) and Behcet's disease (BD) have been discussed previously, however, the results were contradictory. In this study, we thoroughly assess whether MICA-TM gene variants are associated with BD by means of a systematic review and meta analysis. Our study focused on the effects of polymorphisms of MICA-A4, A5, A5.1, A6, and A9 from the included articles. Sixteen previous original publications representing 1,555 BD patients and 2,086 unrelated healthy controls analyzed the association of BD with MICA-TM gene polymorphisms. For the five alleles, MICA-A6 showed a strongly positive correlation with BD patients and could be viewed as an increased risk factor of BD (OR = 2.34, 95%CI: 2.02-2.70). Furthermore, MICA-A4, A5, A5.1, and A9 exhibited negative associations with BD (OR = 0.71, 95%CI: 0.58 0.86; OR = 0.75, 95%CI: 0.63-0.90; OR = 0.63, 95%CI: 0.44-0.91; OR = 0.70, 95%CI: 0.58-0.84, respectively). Our meta-analysis confirmed MICA-A6 could be responsible for BD in three ethnic regions and should probably be treated as a risk factor for BD. MICA-A4, A5, A5.1, and A9 could be regarded as protective factors, especially in the Middle East and East Asia. PMID- 26875670 TI - Population surveys compared with wastewater analysis for monitoring illicit drug consumption in Italy in 2010-2014. AB - BACKGROUND: Monitoring consumption by population surveys (PS) is an important way to challenge the spread of illicit drugs (ID). To improve the information, we explored a complementary method, particularly wastewater analysis (WWA). METHODS: We estimated the prevalence of use by PS, and the consumption by WWA, of cocaine, opioids, cannabis, methamphetamine and MDMA (ecstasy) from 2010 to 2014 in Italy and compared the results. RESULTS: According to PS, cannabis and cocaine were the ID most used in Italy (last month prevalence 3.0% and 0.43% respectively in 2010) followed by opioids (0.17%) and amphetamines (0.14%). WWA gave similar findings, with cannabis consumption (4.35 g THC/day/1000 inhabitants) exceeding cocaine (0.78 g), heroin (0.092 g), methamphetamine and MDMA (0.103 g). The time trend investigated by PS showed significant decreases for all ID from 2010 to 2012. WWA also indicated a reduction of consumption for methamphetamine (p<0.0001) and heroin (p<0.01). Both methods showed an increase for cannabis in 2014 (p<0.001) with the other ID unchanged. Spatial investigations by WWA showed that cannabis and cocaine were consumed significantly more in central Italy than in the north and south. PS indicated the same but only for cannabis. WWA was helpful to study weekly patterns of consumption, showing increases in cocaine and MDMA at weekends. CONCLUSIONS: PS and WWA were confirmed as complementary methods and when used together improved the information on ID use in Italy. We suggest that the combined use of the two approaches can give better information on ID use in the population. PMID- 26875669 TI - Gut immunity in a protochordate involves a secreted immunoglobulin-type mediator binding host chitin and bacteria. AB - Protochordate variable region-containing chitin-binding proteins (VCBPs) consist of immunoglobulin-type V domains and a chitin-binding domain (CBD). VCBP V domains facilitate phagocytosis of bacteria by granulocytic amoebocytes; the function of the CBD is not understood. Here we show that the gut mucosa of Ciona intestinalis contains an extensive matrix of chitin fibrils to which VCBPs bind early in gut development, before feeding. Later in development, VCBPs and bacteria colocalize to chitin-rich mucus along the intestinal wall. VCBP-C influences biofilm formation in vitro and, collectively, the findings of this study suggest that VCBP-C may influence the overall settlement and colonization of bacteria in the Ciona gut. Basic relationships between soluble immunoglobulin type molecules, endogenous chitin and bacteria arose early in chordate evolution and are integral to the overall function of the gut barrier. PMID- 26875671 TI - Is cannabis use associated with an increased risk of onset and persistence of alcohol use disorders? A three-year prospective study among adults in the United States. AB - BACKGROUND: The relationship between cannabis use and alcohol use disorders (AUDs) over time remains unclear. The current study used longitudinal data from adults in the United States (U.S.) to investigate the association between cannabis use and risk of onset and persistence of AUDs three years later. METHODS: The study used data from respondents who completed both waves of the National Epidemiological Study of Alcohol Use and Related Disorders (NESARC; Wave 1, 2001-2001; Wave 2, 2004-2005) and for whom the age of first cannabis use preceded the age of any AUD. Incident AUDs were examined among respondents with no lifetime AUD diagnosis at Wave 1 (n=27,461). Persistent AUDs were examined among respondents with a lifetime AUD diagnosis at Wave 1 (n=2,121). RESULTS: Among adults with no history of AUD, cannabis use at Wave 1 was associated with increased incidence of an AUD three years later relative to no cannabis use (Odds Ratio (OR)=5.43; 95% Confidence Interval (CI)=4.54-6.49). Among adults with a history of AUD, cannabis use at Wave 1 was associated with increased likelihood of AUD persistence three years later relative to no cannabis use (OR=1.74; 95% CI=1.56-1.95). These relationships remained significant after controlling for demographics, psychiatric disorders, and other substance use disorders. CONCLUSIONS: Cannabis use is associated with increased risk of AUD onset and persistence over the course of three years among U.S. adults. Community-based and clinical programs aimed at preventing or treating problematic alcohol use may benefit from integrating information about cannabis use in order to improve outcomes. PMID- 26875672 TI - Non-prescribed use of psychoactive prescription drugs among drug-impaired drivers in Sweden. AB - AIMS: To determine the prevalence of non-prescribed drug use among subjects suspected of drug-impaired driving with a psychoactive prescription drug, and to identify associated factors. METHODS: Subjects investigated for drug-impaired driving in Sweden during 2006-2009 with a confirmed intake of diazepam, flunitrazepam, tramadol, zolpidem or zopiclone were identified using the Swedish Forensic Toxicology Database. Information on dispensed prescription drugs was retrieved from the Swedish Prescribed Drug Register. Non-prescribed use was our outcome, defined as a psychoactive prescription drug intake confirmed by toxicological analysis in a subject by whom it was not dispensed in the 12 months preceding the sampling. Prevalence proportions were calculated for each drug and logistic regression was used to identify associated factors. RESULTS: In total, 2225 subjects were included. The median age (range) was 34 (15-80) years and 1864 (83.8%) subjects were male. Non-prescribed use was found in 1513 subjects (58.7%); for flunitrazepam 103 (76.3%), diazepam 1098 (74.1%), tramadol 192 (40.3%), zopiclone 60 (29.7%), and zolpidem 60 (21.2%) subjects, respectively. Younger age and multiple-substance use were associated with non-prescribed use, whereas ongoing treatment with other psychoactive drugs was negatively associated with non-prescribed use. CONCLUSIONS: Non-prescribed use of psychoactive prescription drugs was common in subjects suspected of drug-impaired driving and was more frequent for benzodiazepines and tramadol compared to zolpidem and zopiclone. The young and multi-substance users were more likely, whereas subjects with ongoing prescribed treatment with other psychoactive drugs were less likely, to use non-prescribed drugs. PMID- 26875673 TI - Qualitative process study of community pharmacist brief alcohol intervention effectiveness trial: Can research participation effects explain a null finding? AB - AIMS: This qualitative process study, nested within a randomised controlled trial evaluating community pharmacist brief alcohol intervention delivery, aims to explore participants' engagement with the trial, so as to identify whether research participation effects may explain why the brief intervention was not found to be effective. METHOD: Qualitative interviews were conducted with 24 randomly selected participants approximately one month after the end of the trial. Semi structured Interviews were conducted by telephone in which participants were asked to give a chronological account of their trial participation, leading to a discussion of possible impacts. These were digitally recorded, transcribed verbatim, and analysed using the Framework method. RESULTS: A range of motivations for taking part in the trial were identified, including pharmacy visitors wanting to obtain an assessment of their drinking. Participants in both arms of the trial spoke of the potent effect that screening had on them. All participants were exposed to discussions about alcohol with empathic pharmacists and, as this is an integral intervention component, this constitutes contamination. Participants' pre-existing ideas about the nature of alcohol problems had an important bearing on how relevant they thought the intervention was to them. CONCLUSION: A detailed appreciation of participant engagement with the trial can provide a strong basis for interpretation of trial outcome data, and in this instance does help explain the null finding. Other findings also indicate the need for dedicated studies of public understanding of the nature of alcohol problems, and their implications for receptivity to brief interventions. PMID- 26875675 TI - Severe halitosis as presentation of epiphrenic diverticulum. AB - Halitosis is a common condition, whose main etiology does not respond to diseases of the gastrointestinal system. Epiphrenic diverticula are a rare cause of this manifestation, thus they are not frequent and they are usually asymptomatic. However, they may produce symptoms with inability for patient. A patient with severe halitosis is presented. In his study, an epiphrenic diverticulum is diagnosed and the laparoscopic abdominal diverticulectomy is performed with a complete resolution of symptomatology. PMID- 26875674 TI - Skeletal manifestations of Marfan syndrome associated to heterozygous R2726W FBN1 variant: sibling case report and literature review. AB - BACKGROUND: FBN1 (15q21.1) encodes fibrillin-1, a large glycoprotein which is a major component of microfibrils that are widely distributed in structural elements of elastic and non-elastic tissues. FBN1 variants are responsible for the related connective tissue disorders, grouped under the generic term of type-1 fibrillinopathies, which include Marfan syndrome (MFS), MASS syndrome (Mitral valve prolapse, Aortic enlargement, Skin and Skeletal findings, Acromicric dysplasia, Familial ectopia lentis, Geleophysic dysplasia 2, Stiff skin syndrome, and dominant Weill-Marchesani syndrome. CASE PRESENTATION: Two siblings presented with isolated skeletal manifestations of MFS, including severe pectus excavatum, elongated face, scoliosis in one case, and absence of other clinical features according to Ghent criteria diagnosis, were screened for detection of variants in whole FBN1 gene (65 exons). Both individuals were heterozygous for the R2726W variant. This variant has been previously reported in association with some skeletal features of Marfan syndrome in the absence of both tall stature and non skeletal features. These features are consistent with the presentation of the siblings reported here. CONCLUSION: The presented cases confirm that the R2726W FBN1 variant is associated with skeletal features of MFS in the absence of cardiac or ocular findings. These findings confirm that FBN1 variants are associated with a broad phenotypic spectrum and the value of sequencing in atypical cases. PMID- 26875676 TI - Evidence of disrupted high-risk human papillomavirus DNA in morphologically normal cervices of older women. AB - High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life. PMID- 26875677 TI - A nomogram to predict the probability of axillary lymph node metastasis in early breast cancer patients with positive axillary ultrasound. AB - Among patients with a preoperative positive axillary ultrasound, around 40% of them are pathologically proved to be free from axillary lymph node (ALN) metastasis. We aimed to develop and validate a model to predict the probability of ALN metastasis as a preoperative tool to support clinical decision-making. Clinicopathological features of 322 early breast cancer patients with positive axillary ultrasound findings were analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of ALN metastasis. A model was created from the logistic regression analysis, comprising lymph node transverse diameter, cortex thickness, hilum status, clinical tumour size, histological grade and estrogen receptor, and it was subsequently validated in another 234 patients. Coefficient of determination (R(2)) and the area under the ROC curve (AUC) were calculated to be 0.9375 and 0.864, showing good calibration and discrimination of the model, respectively. The false-negative rates of the model were 0% and 5.3% for the predicted probability cut-off points of 7.1% and 13.8%, respectively. This means that omission of axillary surgery may be safe for patients with a predictive probability of less than 13.8%. After further validation in clinical practice, this model may support increasingly limited surgical approaches to the axilla in breast cancer. PMID- 26875680 TI - Plant genomics: Under the sea flowering plants adapt and thrive. PMID- 26875678 TI - Unravelling the human genome-phenome relationship using phenome-wide association studies. AB - Advances in genotyping technology have, over the past decade, enabled the focused search for common genetic variation associated with human diseases and traits. With the recently increased availability of detailed phenotypic data from electronic health records and epidemiological studies, the impact of one or more genetic variants on the phenome is starting to be characterized both in clinical and population-based settings using phenome-wide association studies (PheWAS). These studies reveal a number of challenges that will need to be overcome to unlock the full potential of PheWAS for the characterization of the complex human genome-phenome relationship. PMID- 26875681 TI - Evidence from Multiple Species that Spider Silk Glue Component ASG2 is a Spidroin. AB - Spiders in the superfamily Araneoidea produce viscous glue from aggregate silk glands. Aggregate glue coats prey-capture threads and hampers the escape of prey from webs, thereby increasing the foraging success of spiders. cDNAs for Aggregate Spider Glue 1 (ASG1) and 2 (ASG2) have been previously described from the golden orb-weaver, Nephila clavipes, and Western black widow, Latrodectus hesperus. To further investigate aggregate glues, we assembled ASG1 and ASG2 from genomic target capture libraries constructed from three species of cob-web weavers and three species of orb-web weavers, all araneoids. We show that ASG1 is unlikely to be a glue, but rather is part of a widespread arthropod gene family, the peritrophic matrix proteins. For ASG2, we demonstrate its remarkable architectural and sequence similarities to spider silk fibroins, indicating that ASG2 is a member of the spidroin gene family. Thus, spidroins have diversified into glues in addition to task-specific, high performance fibers. PMID- 26875679 TI - Cheating evolution: engineering gene drives to manipulate the fate of wild populations. AB - Engineered gene drives - the process of stimulating the biased inheritance of specific genes - have the potential to enable the spread of desirable genes throughout wild populations or to suppress harmful species, and may be particularly useful for the control of vector-borne diseases such as malaria. Although several types of selfish genetic elements exist in nature, few have been successfully engineered in the laboratory thus far. With the discovery of RNA guided CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats CRISPR-associated 9) nucleases, which can be utilized to create, streamline and improve synthetic gene drives, this is rapidly changing. Here, we discuss the different types of engineered gene drives and their potential applications, as well as current policies regarding the safety and regulation of gene drives for the manipulation of wild populations. PMID- 26875683 TI - Effect of angiotensin receptor blockade on central aortic systolic blood pressure in hypertensive Asians measured using radial tonometry: an open prospective cohort study. AB - INTRODUCTION: Central aortic systolic pressure (CASP) has been shown to be a stronger predictor of cardiovascular events than brachial blood pressure (BP). Different classes of drugs have differential effects on CASP and brachial BP. This open prospective cohort study aimed to observe changes in CASP (measured using radial tonometry) among hypertensive Asians after 12 weeks of treatment with valsartan, an angiotensin receptor blocker (ARB). METHODS: Patients with treatment-naive hypertension or uncontrolled hypertension who were on non-ARB therapy were eligible for inclusion. Patients with uncontrolled BP (i.e. >= 140/90 mmHg) received valsartan for 12 weeks. The patients' brachial systolic and diastolic BP (SBP and DBP), and CASP changes were monitored using the BPro(r) watch. RESULTS: The mean age of the 44 enrolled patients was 35 years. At baseline, the mean BP and CASP were 150.2/91.4 +/- 10.6/9.4 mmHg and 136.3 +/- 12.2 mmHg, respectively. Valsartan reduced SBP, DBP and CASP by 14.9 +/- 10.7 mmHg, 10.9 +/- 8.4 mmHg and 15.3 +/- 10.9 mmHg, respectively (all p < 0.001). Every 1.0-mmHg reduction in brachial SBP resulted in a 0.8-mmHg reduction in CASP (p < 0.001). A CASP cut-off of 122.5 mmHg discriminated between controlled and uncontrolled BP (sensitivity 74%, specificity 88%). CONCLUSION: Using radial tonometry, we demonstrated good correlation between CASP and brachial SBP reductions after 12 weeks of treatment with valsartan in our study cohort. Correlation analysis between CASP and SBP reductions may be useful for demonstrating whether a drug is able to lower CASP beyond lowering SBP. PMID- 26875682 TI - Early outcome of transurethral enucleation and resection of the prostate versus transurethral resection of the prostate. AB - INTRODUCTION: Recurrent prostate adenoma is a long-term complication following transurethral resection of the prostate (TURP). Transurethral enucleation and resection of the prostate (TUERP) is more appealing, since the nodular adenoma can be completely removed through endoscopy. TUERP is also hypothesised to result in a lower frequency of recurrent adenoma. This study aimed to compare the early outcomes of TUERP and TURP, and assess the feasibility and safety of TUERP. METHODS: We compared the outcome of 81 patients who underwent TUERP with that of 85 patients who underwent TURP. International prostate symptom score, quality of life score, prostate volume, degree of intravesical prostatic protrusion, maximum flow rate, post-void residual volume and prostate-specific antigen (PSA) level were obtained pre- and postoperatively. Complications (e.g. transfusion rate, incontinence, infection and urethral stricture) were analysed. RESULTS: Operative time was significantly longer in the TUERP group compared to the TURP group (85.3 minutes vs. 51.6 minutes). After TUERP, the maximum flow rate was significantly higher (21.1 mL/s vs. 17.1 mL/s) and PSA level was significantly lower (1.2 ng/mL vs. 1.9 ng/mL) than after TURP. The rates of infection, transfusion and urethral stricture were similar for both groups, but the TUERP group had a higher rate of temporary incontinence (13.6% vs. 4.7%). CONCLUSION: The lower PSA level and better maximum flow rate achieved following TUERP suggest that prostate adenoma removal was more complete with TUERP. Long-term follow-up is required to establish whether TUERP results in fewer resections for recurrent adenoma. PMID- 26875684 TI - Detection of Vaccinia virus during an outbreak of exanthemous oral lesions in Brazilian equids. AB - REASONS FOR PERFORMING STUDY: In August 2014, an outbreak of oral exanthematous disease in equids was reported in Brazil, affecting 11 donkeys and 3 mules. OBJECTIVES: To investigate if Vaccinia virus (VACV) was the aetiological agent in this outbreak. STUDY DESIGN: Investigation of clinical cases using serological, molecular and phylogenetic approaches. METHODS: To analyse the presence of neutralising antibodies against VACV, samples were submitted in triplicate to a plaque-reduction neutralisation test (PRNT50% ). On the basis of previous studies which detected VACV DNA in sera, we submitted extracted DNA samples to different polymerase chain reaction (PCR) platforms targeting Orthopoxvirus (OPV) genes (C11R, A56R and A26L). The PCR products were directly sequenced in both orientations using specific primers and capillary electrophoresis. The alignment and phylogenetic analysis of the A26L and A56R nucleotide sequences (maximum likelihood) were prepared with the obtained nucleotide fragments. RESULTS: Serological and molecular data suggested VACV as the aetiological agent. The neutralising antibodies against OPV were detected in 5 (55.5%) of the equids, with titres >=40 neutralising u/ml. Based on the results obtained from all PCR platforms, all samples were positive for OPV: 9 (100%) for A56R, 4 (44.4%) for C11R and 3 (33.3%) for A26L. The alignment of the nucleotide sequences of the A26L and A56R fragments revealed that the samples were highly similar to the homologous genes from other Brazilian VACV Group 1 isolates (98.8% identity on average). Furthermore, both the A26L and A56R sequences showed signature deletions also present in the sequences of Group 1 VACV isolates from Brazil. CONCLUSIONS: Our data raises questions about the role of equids in the chain of VACV epidemiology. The surveillance of equids in VACV-affected areas worldwide is relevant. PMID- 26875685 TI - Quantum-mechanical machinery for rational decision-making in classical guessing game. AB - In quantum game theory, one of the most intriguing and important questions is, "Is it possible to get quantum advantages without any modification of the classical game?" The answer to this question so far has largely been negative. So far, it has usually been thought that a change of the classical game setting appears to be unavoidable for getting the quantum advantages. However, we give an affirmative answer here, focusing on the decision-making process (we call 'reasoning') to generate the best strategy, which may occur internally, e.g., in the player's brain. To show this, we consider a classical guessing game. We then define a one-player reasoning problem in the context of the decision-making theory, where the machinery processes are designed to simulate classical and quantum reasoning. In such settings, we present a scenario where a rational player is able to make better use of his/her weak preferences due to quantum reasoning, without any altering or resetting of the classically defined game. We also argue in further analysis that the quantum reasoning may make the player fail, and even make the situation worse, due to any inappropriate preferences. PMID- 26875686 TI - Corrigendum: ImmuSort, a database on gene plasticity and electronic sorting for immune cells. PMID- 26875687 TI - Boron induced structure modifications in Pd-Cu-B system: new Ti2Ni-type derivative borides Pd3Cu3B and Pd5Cu5B2. AB - The formation of two distinct derivative structures of Ti2Ni-type, interstitial Pd3Cu3B and substitutive Pd5Cu5B2, has been elucidated in Pd-Cu-B alloys from analysis of X-ray single crystal and powder diffraction data and supported by SEM. The metal atom arrangement in the new boride Pd3Cu3B (space group Fd3m, W3Fe3C-type structure, a = 1.1136(3) nm) follows the pattern of atom distribution in the CdNi-type structure. Pd5Cu5B2 (space group F(4)3m, a = 1.05273(5) nm) exhibits a non-centrosymmetric substitutive derivative of the Ti2Ni-type structure. The reduction of symmetry on passing from Ti2Ni-type structure to Pd5Cu5B2 corresponds to the loss of an inversion centre delivered by an ordered occupation of the Ni position (32e) by dissimilar atoms, Cu and B. In both structures, the boron atom centers Pd forming [BPd6] octahedra in Pd3Cu3B and [BPd6] trigonal prisms in Pd5Cu5B2. Neither a perceptible homogeneity range nor mutual solid solubility was observed for two compounds at 600 degrees C, while in as cast conditions Pd5Cu5B2 exhibits an extended homogeneity range formed by a partial substitution of Cu atoms (in 24f) by Pd (Pd5+xCu5-xB2, 0 <=x<= 1). Electrical resistivity measurements performed on Pd3Cu3B as well as on Pd-poor and Pd-rich termini of Pd5+xCu5-xB2 annealed at 600 degrees C and in as cast conditions respectively demonstrated the absence of any phase transitions for this compounds in the temperature region from 0.3 K to 300 K. PMID- 26875688 TI - Hyperammonemia alters glycinergic neurotransmission and modulation of the glutamate-nitric oxide-cGMP pathway by extracellular glycine in cerebellum in vivo. AB - The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the cerebellum and induces cognitive impairment. The possible alterations in hyperammonemia of glycinergic neurotransmission and of glutamate-NO-cGMP pathway modulation by glycine remain unknown. The aims were to assess, by in vivo microdialysis in cerebellum: (i) the effects of different glycine concentrations, administered through the microdialysis probe, on the glutamate-NO-cGMP pathway function; (ii) the effects of tonic glycine receptors activation on the pathway function, by blocking them with strychnine; (iii) whether hyperammonemia alters the pathway modulation by glycine; (iv) and whether hyperammonemia alters extracellular glycine concentration and/or glycine receptor membrane expression. In control rats, low glycine levels reduce the pathway function, likely by activating glycine receptors, while 20 MUM glycine enhances the pathway function, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine did not reduce the pathway function, but enhanced it when administered at 1-20 MUM. Hyperammonemia reduces extracellular glycine concentration by approximately 50% and glycine receptor membrane expression. However, tonic glycine receptor activation seems to be enhanced in hyperammonemic rats, as indicated by the larger increase in extracellular cGMP induced by strychnine. These data show that glycine modulates the glutamate-NO-cGMP pathway biphasically and that hyperammonemia strongly alters glycinergic neurotransmission and modulation by glycine of the glutamate-NO-cGMP pathway. These alterations may contribute to the cerebellar aspects of cognitive alterations in hyperammonemia. The findings reported in this study show that hyperammonemia alters glycinergic neurotransmission and the glutamate-NO-cGMP pathway modulation by glycine. In control rats, low glycine levels reduced the pathway function, likely by activating glycine receptors, while 20 MUM glycine enhanced the pathway, likely by enhancing NMDA receptor activation. In hyperammonemic rats, glycine (administered at 1-20 MUM) enhances the pathway, likely by activating NMDA receptors. PMID- 26875689 TI - Water Dynamics in Gyroid Phases of Self-Assembled Gemini Surfactants. AB - Water-mediated ion transport through functional nanoporous materials depends on the dynamics of water confined within a given nanostructured morphology. Here, we investigate H-bonding dynamics of interfacial water within a "normal" (Type I) lyotropic gyroid phase formed by a gemini dicarboxylate surfactant self-assembly using a combination of 2DIR spectroscopy and molecular dynamics simulations. Experiments and simulations demonstrate that water dynamics in the normal gyroid phase is 1 order of magnitude slower than that in bulk water, due to specific interactions between water, the ionic surfactant headgroups, and counterions. Yet, the dynamics of water in the normal gyroid phase are faster than those of water confined in a reverse spherical micelle of a sulfonate surfactant, given that the water pool in the reverse micelle and the water pore in the gyroid phase have roughly the same diameters. This difference in confined water dynamics likely arises from the significantly reduced curvature-induced frustration at the convex interfaces of the normal gyroid, as compared to the concave interfaces of a reverse spherical micelle. These detailed insights into confined water dynamics may guide the future design of artificial membranes that rapidly transport protons and other ions. PMID- 26875690 TI - Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo. AB - Prostate cancer is highly prevalent and has become the second leading cause of cancer-related death in men. Its treatment remains a challenge in the clinic, particularly in patients who have advanced to "castration-resistant prostate cancer" (CRPC). Thus, more effective therapeutic strategies are required. Quercetin (QCT) is a natural flavonoid compound that has attracted increasing interest due to its anticancer activity. However, the clinical application of quercetin is largely hampered by its poor water solubility and low bioavailability. The objective of this study was to evaluate the therapeutic potential of novel QCT-loaded nanomicelles (M-QCTs) assembled from DSPE-PEG2000 for prostate cancer treatment. Our results indicated that QCT was efficiently encapsulated into micelles up to 1 mg mL(-1), which corresponds to a 450-fold increase of its water solubility. In vitro studies showed that the half-maximal inhibitory concentration (IC50) value (20.2 MUM) of M-QCTs was much lower than free QCT (>200 MUM). Thus, M-QCTs were considerably more effective than free QCT in proliferation inhibition and apoptosis induction of human androgen-independent PC-3 cells. Furthermore, M-QCTs showed superior antitumor efficacy and the tumor proliferation rate reduced by 52.03% compared to the control group in the PC-3 xenograft mouse model, possibly due to increased accumulation of M-QCTs at the tumor site by the enhanced permeability and retention (EPR) effect. Collectively, our studies demonstrated that M-QCTs significantly increase drug accumulation at the tumor site and exhibit superior anticancer activity in prostate cancer. Thus, our nanomicelle-based drug delivery system constitutes a promising and effective therapeutic strategy for clinical treatment. PMID- 26875691 TI - Application of hollow fiber vitrification for cryopreservation of bovine early cleavage stage embryos and porcine morula-blastomeres. AB - A novel hollow fiber vitrification (HFV) method was applied to materials that have previously been difficult to cryopreserve, thereby expanding the potential application of this method. The results showed that zona-free porcine morulae and their isolated blastomeres remained viable even after vitrification. The rate of development to blastocysts after vitrification was similar for zona-free and zona intact morulae (21/23, 91.3% for both). Vitrified blastomeres had a developmental potential equal to that of non-vitrified blastomeres (blastocyst formation rate after reaggregation: 16/17, 94.1% for both). The HFV method was also effective for the cryopreservation of in vitro matured/fertilized bovine embryos at the 2- to 4-cell, 8- to 16-cell and morula stages. The blastocyst formation rates of vitrified embryos (66.1-82.5%) were similar to those of non-vitrified embryos (74.5-82.5%). These results indicate that this novel HFV method is an effective tool for embryo cryopreservation that can enhance current practices in reproductive biology. PMID- 26875692 TI - Defect engineering of UiO-66 for CO2 and H2O uptake - a combined experimental and simulation study. AB - Defect concentrations and their compensating groups have been systematically tuned within UiO-66 frameworks by using modified microwave-assisted solvothermal methods. Both of these factors have a pronounced effect on CO2 and H2O adsorption at low and high pressure. PMID- 26875693 TI - A Variable Temperature Synchrotron X-ray Diffraction Study of Colossal Magnetoresistant NdMnAsO0.95F0.05. AB - The recent discovery of high temperature superconductivity in Fe arsenides has invigorated research into transition metal pnictides. Colossal magnetoresistance (CMR) has recently been reported for NdMnAsO1-xFx for x = 0.05-0.08, with a maximum magnetoresistance achieved at low temperature (MR9T(3 K)) = -95%). This appears to be a novel mechanism of CMR, which is as a result of a second order phase transition in field from an insulating antiferromagnet to a semiconducting paramagnet. Here we report a variable temperature synchrotron X-ray powder diffraction study of the CMR oxypnictide NdMnAsO0.95F0.05 between 4 K-290 K. An excellent fit to the tetragonal unit cell with space group P4/nmm is obtained over the entire temperature range, with no change in crystal structure detected down to 4 K. A coupling of the lattice and magnetic order is observed, where subtle discontinuities in the temperature variation of a and the c/a ratio are apparent as the Nd spins order antiferromagnetically and the Mn moments reorient into the basal plane at TSR. The results suggest that very small changes in lattice parameters effect the coupling between lattice, electronic and magnetic degrees of freedom. PMID- 26875694 TI - Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron astrocyte interaction in the dentate gyrus. AB - Childhood trauma is a well-described risk factor for the development of stress related psychopathology such as posttraumatic stress disorder or depression later in life. Childhood adversity can be modeled in rodents by juvenile stress (JS) protocols, resulting in impaired coping with stressful challenges in adulthood. In the current study, we investigated the long-lasting impact of JS on the expression of molecular factors for glutamate and gamma-aminobutyric acid (GABA) uptake and turnover in sublayers of the dentate gyrus (DG) using laser microdissection and quantitative real-time polymerase chain reaction. We observed reduced mRNA expression levels after JS for factors mediating astrocytic glutamate and GABA uptake and degradation. These alterations were prominently observed in the dorsal but not ventral DG granule cell layer, indicating a lasting change in astrocytic GABA and glutamate metabolism that may affect dorsal DG network activity. Indeed, we observed increased inhibition and a lack of facilitation in response to paired-pulse stimulation at short interstimulus intervals in the dorsal DG after JS, while no alterations were evident in basal synaptic transmission or forms of long-term plasticity. The shift in paired-pulse response was mimicked by pharmacologically blocking the astrocytic GABA transporter GAT-3 in naive animals. Accordingly, reduced expression levels of GAT 3 were confirmed at the protein level in the dorsal granule cell layer of rats stressed in juvenility. Together, these data demonstrate a lasting shift in the excitatory/inhibitory balance of dorsal DG network activity by JS that appears to be mediated by decreased GABA uptake into astrocytes. PMID- 26875697 TI - Etching of electrodeposited Cu2O films using ammonia solution for photovoltaic applications. AB - Impurities at the surface of electrodeposited p-Cu2O films have been efficiently removed through the use of concentrated aqueous ammonia solution as a wet etching agent. The performance of the Cu2O homojunction photovoltaic devices incorporating etched p-Cu2O as the bottom layer is higher compared to devices with as-deposited p-Cu2O layers due to an improvement of the homojunction interface quality. Reducing the density of defect states that act as carrier recombination centers led to larger open circuit voltages. The ammonia etchant has been found to preferentially interact with the {100} facets of Cu2O and expose a greater number of {111} facets, resulting in increased interface area for etched homojunction devices, which also improved short circuit current density values. PMID- 26875695 TI - Conformational plasticity of RepB, the replication initiator protein of promiscuous streptococcal plasmid pMV158. AB - DNA replication initiation is a vital and tightly regulated step in all replicons and requires an initiator factor that specifically recognizes the DNA replication origin and starts replication. RepB from the promiscuous streptococcal plasmid pMV158 is a hexameric ring protein evolutionary related to viral initiators. Here we explore the conformational plasticity of the RepB hexamer by i) SAXS, ii) sedimentation experiments, iii) molecular simulations and iv) X-ray crystallography. Combining these techniques, we derive an estimate of the conformational ensemble in solution showing that the C-terminal oligomerisation domains of the protein form a rigid cylindrical scaffold to which the N-terminal DNA-binding/catalytic domains are attached as highly flexible appendages, featuring multiple orientations. In addition, we show that the hinge region connecting both domains plays a pivotal role in the observed plasticity. Sequence comparisons and a literature survey show that this hinge region could exists in other initiators, suggesting that it is a common, crucial structural element for DNA binding and manipulation. PMID- 26875698 TI - Unique features associated with hepatic oxidative DNA damage and DNA methylation in non-alcoholic fatty liver disease. AB - BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC). Previously, we reported that DNA oxidation induced epigenetic alteration of tumor suppressor genes (TSGs) and contributed to HCC emergence. Here, we examine the associations between clinicopathological characteristics of NAFLD and advanced oxidative DNA damage that is associated with TSG methylation in the NAFLD liver. METHODS: Liver biopsies from 65 NAFLD patients were analyzed for clinicopathological features and oxidative DNA damage using immunohistochemistry of 8-hydroxydeoxyguanosine (8 OHdG). Abnormal DNA methylation in the promoters of 6 TSGs, HIC1, GSTP1, SOCS1, RASSF1, CDKN2A, and APC, was examined using MethyLight. Associations between clinicopathological characteristics, methylation of TSGs, and accumulation of 8 OHdG were analyzed. RESULTS: We found that aspartate aminotransferase/alanine aminotransferase ratio, the fibrosis-4 index, and serum alpha-fetoprotein (AFP) level were associated with degree of 8-OHdG, and AFP was an independent factor among them (P = 0.0271). Regarding pathological findings, hepatocellular ballooning and stage of fibrosis were also associated with oxidative DNA damage (P = 0.0021 and 0.0054); ballooning was an independent risk for detecting high degree of 8-OHdG in hepatocytes (odds ratio 7.38, 95% confidence interval 1.41 49.13, P = 0.0171). Accumulation of methylated TSGs was significantly associated with deposition of 8-OHdG (P = 0.0362). CONCLUSIONS: Patients with high serum AFP and high degree of ballooning showed accumulation of oxidative DNA damage that could be a seed of DNA methylation responsible for hepatocarcinogenesis. These characteristics could be risk of HCC; such patients require urgent intervention such as lifestyle modification. PMID- 26875699 TI - Exploring barriers to and facilitators of preventive measures against infectious diseases among Australian Hajj pilgrims: cross-sectional studies before and after Hajj. AB - OBJECTIVE: For reasons that have yet to be elucidated, the uptake of preventive measures against infectious diseases by Hajj pilgrims is variable. The aim of this study was to identify the preventive advice and interventions received by Australian pilgrims before Hajj, and the barriers to and facilitators of their use during Hajj. METHODS: Two cross-sectional surveys of Australians pilgrims aged >=18 years were undertaken, one before and one after the Hajj 2014. RESULTS: Of 356 pilgrims who completed the survey (response rate 94%), 80% had the influenza vaccine, 30% the pneumococcal vaccine, and 30% the pertussis vaccine. Concern about contracting disease at Hajj was the most cited reason for vaccination (73.4%), and not being aware of vaccine availability was the main reason for non-receipt (56%). Those who obtained pre-travel advice were twice as likely to be vaccinated as those who did not seek advice. Of 150 pilgrims surveyed upon return, 94% reported practicing hand hygiene during Hajj, citing ease of use (67%) and belief in its effectiveness (62.4%) as the main reasons for compliance; university education was a significant predictor of hand hygiene adherence. Fifty-three percent used facemasks, with breathing discomfort (76%) and a feeling of suffocation (40%) being the main obstacles to compliance. CONCLUSION: This study indicates that there are significant opportunities to improve awareness among Australian Hajj pilgrims about the importance of using preventive health measures. PMID- 26875700 TI - Vapor deposition of a smectic liquid crystal: highly anisotropic, homogeneous glasses with tunable molecular orientation. AB - Physical vapor deposition (PVD) has been used to prepare glasses of itraconazole, a smectic A liquid crystal. Glasses were deposited onto subtrates at a range of temperatures (Tsubstrate) near the glass transition temperature (Tg), with Tsubstrate/Tg ranging from 0.70 to 1.02. Infrared spectroscopy and spectroscopic ellipsometry were used to characterize the molecular orientation using the orientational order parameter, Sz, and the birefringence. We find that the molecules in glasses deposited at Tsubstrate = Tg are nearly perpendicular to the substrate (Sz = +0.66) while at lower Tsubstrate molecules are nearly parallel to the substrate (Sz = -0.45). The molecular orientation depends on the temperature of the substrate during preparation, allowing layered samples with differing orientations to be readily prepared. In addition, these vapor-deposited glasses are macroscopically homogeneous and molecularly flat. We interpret the combination of properties obtained for vapor-deposited glasses of itraconazole to result from a process where molecular orientation is determined by the structure and dynamics at the free surface of the glass during deposition. Vapor deposition of liquid crystals is likely a general approach for the preparation of highly anisotropic glasses with tunable molecular orientation for use in organic electronics and optoelectronics. PMID- 26875701 TI - Towards nanometer-spaced silicon contacts to proteins. AB - A vertical nanogap device (VND) structure comprising all-silicon contacts as electrodes for the investigation of electronic transport processes in bioelectronic systems is reported. Devices were fabricated from silicon-on insulator substrates whose buried oxide (SiO2) layer of a few nanometers in thickness is embedded within two highly doped single crystalline silicon layers. Individual VNDs were fabricated by standard photolithography and a combination of anisotropic and selective wet etching techniques, resulting in p(+) silicon contacts, vertically separated by 4 or 8 nm, depending on the chosen buried oxide thickness. The buried oxide was selectively recess-etched with buffered hydrofluoric acid, exposing a nanogap. For verification of the devices' electrical functionality, gold nanoparticles were successfully trapped onto the nanogap electrodes' edges using AC dielectrophoresis. Subsequently, the suitability of the VND structures for transport measurements on proteins was investigated by functionalizing the devices with cytochrome c protein from solution, thereby providing non-destructive, permanent semiconducting contacts to the proteins. Current-voltage measurements performed after protein deposition exhibited an increase in the junctions' conductance of up to several orders of magnitude relative to that measured prior to cytochrome c immobilization. This increase in conductance was lost upon heating the functionalized device to above the protein's denaturation temperature (80 degrees C). Thus, the VND junctions allow conductance measurements which reflect the averaged electronic transport through a large number of protein molecules, contacted in parallel with permanent contacts and, for the first time, in a symmetrical Si-protein-Si configuration. PMID- 26875702 TI - Synovial sarcoma presenting as a lung mass and diagnosed by cytology. AB - Synovial sarcoma is a common soft tissue sarcoma with variable fibrous and epithelial differentiation that rarely arises from other body sites, such as within the lung. A case of a 68-year-old male with an extensive smoking history who presented with chest pain and a primary, central, metabolically active lung mass was reported. The mass was biopsied by bronchial brushing, bronchoalveolar lavage (BAL), and transbronchial fine-needle aspiration (FNA). Cytologic analysis of bronchial brushing, BAL, and FNA revealed single and clusters of atypical spindle cells, oval, or spindle-shaped nuclei with smooth nuclear membranes, hyperchromatic and granular chromatin, scant to moderate and delicate cytoplasm, a high degree of mitotic figures, and a lack of necrosis. Immunohistochemical studies showed that the tumor cells were positive for CD99, BCL2, and CK7. A diagnosis of synovial sarcoma was rendered. The differential diagnosis of primary pulmonary synovial sarcoma is discussed, including neuroendocrine tumors, squamous cell carcinoma, and various sarcomatous tumors. PMID- 26875705 TI - Endoscopic endonasal study of the cavernous sinus and quadrangular space: Anatomic relationships. AB - BACKGROUND: The quadrangular space permits an anterior entry into Meckel's cave while obviating the need for cerebral or cranial nerve retraction. This avenue is intimately associated with the cavernous sinus; thus, from this ventral perspective, it is feasible to visualize the anteromedial, anterolateral, and Parkinson triangles. METHODS: Twenty middle cranial fossae were dissected endonasally under direct endoscopic visualization. Measurements of the surface area of the quadrangular space and the ventrally accessible cavernous sinus triangles were performed using 3 coordinates under image-guided navigation. RESULTS: The surface area of the quadrangular space was 16.36 mm(2) (+/-2.89 mm(2) ). The anterolateral triangle was the largest (47.27 +/- 5.37 mm(2) ), whereas Parkinson's was the smallest (22.46 +/- 5.54 mm(2) ); the anteromedial triangle presented an average surface area 36.07 mm(2) (+/-4.15 mm(2) ). CONCLUSION: The trajectory of the internal carotid artery (ICA) significantly impacts the quadrangular space area and may be a potential parameter for defining the feasibility of this corridor. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1680-E1687, 2016. PMID- 26875706 TI - Headache and Chronic Subdural Hematoma. PMID- 26875707 TI - [Focus on vestibular migraine]. PMID- 26875708 TI - [Correlations between constipation and the axial symptoms, related motor symptoms in Parkinson's disease]. AB - OBJECTIVE: To investigate the clinical characteristics of Parkinson's Disease (PD) patients with constipation and explore the correlation between constipation and motor symptoms. METHODS: The demographic data of outpatients with PD in our hospital was collected. According to Rome III criteria, we evaluated the status of constipation in PD patients. Unified Parkinson's disease rating scale part III (UPDRSIII), mini-mental state examination (MMSE) were performed in all the included patients. RESULTS: Among the 158 recruited PD patients, 96 (60.8%) patients had constipation. Among these patients, 41(42.7%) patients experienced constipation before motor symptoms. Compared to those without constipation, PD patients with constipation had higher axial scores (6.8+/-3.4 vs 4.3+/-2.5, t= 4.887, P=0.000) and gait/postural stability scores (3.9+/-2.4 vs 2.4+/-1.5, t= 4.529, P=0.000), higher proportion of axial and gait/postural stability scores in UPDRSIII (32%+/-11% vs 25%+/-12%, t=-3.485, P=0.001; 18%+/-9% vs 15%+/-10%, t= 2.278, P=0.024), more rapid progression of axial and gait/postural stability symptoms (P<0.05). However, there were no differences in other sub-scores and progression of motor symptoms between the two groups (P>0.05). The PD patients with constipation preceding motor symptoms had higher proportion of axial and gait/postural stability scores in UPDRSIII (35%+/-11% vs 30%+/-10%, t=2.167, P=0.033; 21%+/-9% vs 16%+/-8%, t=2.733, P=0.008), indicating these patients may progress more rapidly, meanwhile, they had later onset age, shorter disease duration (P<0.05). Unconditioned Logistic regression showed that axial score was major influencing factor of constipation in PD patients (P=0.000, OR=1.330). CONCLUSIONS: PD patients with constipation have severer axial symptoms, indicating the progression of these patients is relatively rapid, especially those with constipation preceding motor symptoms. It is suggested that axial symptoms and constipation are acted as interactional factors in PD. PMID- 26875709 TI - [Virtual unenhanced images derived from spectral CT imaging accessing gastric carcinoma: a feasible study]. AB - OBJECTIVE: To qualitatively and quantitatively compare MSI images and WB images derived from spectral CT imaging with CU images in accessing gastric carcinoma. METHODS: The clinical data and imaging findings of 91 cases of gastric carcinomas between December 2013 and May 2015 were analyzed retrospectively. All patients underwent CU CT and enhanced CT with spectral imaging in AP and VP. MSI images were reconstructed based on monochromatic images of 70 keV in AP. WB images were obtained by water-iodine pair substance isolation of the AP images. Two abdominal radiologists independently evaluated the image quality and the depiction of gastric carcinoma in CU, MSI and WB images using a 5-point scale. The sensitivities of gastric cancer were evaluated by using enhanced images as the reference standard.The CT number of various regions, image noise, relative enhancement CT value of tumors and metastasis were measured and calculated on CU and MSI images. The CNR of gastric tumor were measured on CU, MSI and WB images. Effective radiation doses for triple-phase and dual-phase scan were calculated. Differences were tested for statistical significance using the Wilcoxon's signed rank test and the paired t-test. RESULTS: Interobserver agreement with regard to image quality and the depiction of gastric carcinoma was good(all kappa>0.70). There was no statistical significant difference in image quality between CU(4.30+/-0.63) and MSI(4.17+/-0.58) images(P>0.05), both higher than WB(3.87+/ 0.84) images (both P<0.01). The depiction of gastric carcinoma in CU(3.86+/-0.50) and MSI(3.73+/-0.55) images had no statistical significant difference (P>0.05), and both higher than WB(3.34+/-0.38) images( both P<0.01). The sensitivities of CU, MSI and WB images were 91.2%, 95.6%, 93.4%. The CT number of gastric tumors, liver metastasis and aorta, image noise on MSI images were slightly higher than on TNE images(P<0.05). The CT number of gastric tumors, liver metastasis and aorta, image noise on MSI images were slightly higher than on TNE images(P<0.05). The CT number of lymph nodes, liver and muscle, CT relative enhancement value of gastric tumors, lymph nodes and liver metastasis had no significant difference between TNE and MSI images (all P>0.05). The CNR of gastric tumors had significant difference between groups: WB images were higher than MSI and MSI were higher than CU images(all P<0.01). The dose saving by removing the CU was 8.2 mSv(32%). CONCLUSION: The MSI images derived from spectral CT can provide comparable image quality to CU images and reliable diagnostic information for gastric tumors, which is superior to WB images, replacing CU images will lower radiation exposure by 32%. PMID- 26875710 TI - [Anterior and posterior default mode networks impairments in minimal hepatic encephalopathy]. AB - OBJECTIVE: To investigate the functional connectivity (FC) impairments within anterior and posterior default mode networks (aDMN and pDMN) for cirrhosis with minimal hepatic encephalopathy (MHE), and to analyze relationship between DMNs alterations with neurocognitive impairments. METHODS: From March 2009 to December 2011, a total of 43 cirrhotic patients without MHE (NMHE groups), 32 cirrhotic patients with current MHE (MHE groups), and 21 healthy controls were recruited in this study. All resting-state fMRI datasets were preprocessed and normalized into standard brain space. Two universal templates for aDMN and pDMN were applied to generate spatial patterns for aDMN and pDMN for each participate by dual regression. One sample t test were analyzed within groups, and one way ANOVA (analysis of variance) were performed to calculate the different FCs within aDMN and pDMN among groups. Additional correlation analysis was performed between different FCs within two DMNs and behavior scores. RESULTS: Within aDMN, FC of MHE patients were significantly deceased than controls and NMHE groups in right superior frontal gyrus (SFG)/ bilateral medial frontal gyrus (MFG); while within pDMN, FC of MHE patients were significantly increased than controls and NMHE groups in right superior temporal gyrus (STG)/ middle temporal gyrus (MTG) and left cuneus/ bilateral calcarine gyri (one way ANOVA, P<0.01, cluster sizes>40, AlphaSim correction). The FC alterations in those region were significantly correlated with neurocognitive test scores (Pearson correlation coefficient, P<0.05). CONCLUSION: Dual regression based aDMN and pDMN method was firstly applied to investigated functional connectivity impairments in MHE patients' brain. Functional deficits were endogenous within aDMN, while functional connectivity was compensatory enhancements within pDMN. These compensatory enhancements indicated that patients with current MHE had the potential to additionally recruit more neurological resource to accomplish the specific actions. Therefore, the alterations of dual regression based aDMN and pDMN can be potential neuroimaging biomarkers for MHE studies. PMID- 26875711 TI - [Establishment of reference ranges for thyroid-related indicators in normal pregnant women]. AB - OBJECTIVE: To establish the gestational age-specific reference ranges for thyroid related indicators of pregnant women in our hospital, especially for serum thyroid stimulating hormone (TSH) in the first trimester. METHODS: A total of 548 pregnant women in the first trimester were collected in Peking University First Hospital from June 2013 to April 2014. Among them, 254 pregnant women with single fetus who conformed to the National Academy of Clinical Biochemistry criteria, without adverse pregnancy outcomes and obstetric complications, were enrolled in the current study. To establish their own self-sequential longitudinal reference intervals, serum TSH, total thyroxine (TT4) and free thyroxine (FT4) levels were measured using Siemens detection kits during three different trimesters. Urine iodine (UI) was measured using digestion instrument in some of the pregnant women. RESULTS: The gestational age-specific reference ranges for thyroid-related indicators of pregnant women in our hospital were as follows: in the first trimester: TSH 0.23-4.08 mU/L, TT4 92.59-186.25 nmol/L, FT4 13.36-20.81 pmol/L; in the second trimester: TSH 0.78-4.25 mU/L, TT4 103.20-180.95 nmol/L, FT4 11.57 16.62 pmol/L; in the third trimester: TSH 0.65-4.52 mU/L, TT4 78.20-174.70 nmol/L, FT4 10.01-20.57 pmol/L. The median level of TSH during 7 to 12 weeks of gestational age was lower than that of 4 to 6 weeks, but with no significant statistical difference (P=0.063). The medians of UI during three trimesters of pregnancy were 211.60 MUg/L, 195.55 MUg/L and 198.65 MUg/L, respectively, which were all classified as adequate iodine status. CONCLUSIONS: The gestational age specific reference ranges for thyroid-related indicators are different from the kits' reference ranges, which are also different among the three trimesters. It may be more reasonable to establish different reference ranges for thyroid related indicators at 4 to 6 weeks and 7 to 12 weeks in the first trimester separately. PMID- 26875712 TI - [Digital design of internal fixation for distal femoral fractures via 3D printing and standard parts database]. AB - OBJECTIVE: To study the method of internal fixation by the navigation embedded plate from standard parts database for the distal femoral fractures based on digital design by Mimics software with 3D printing technology, and to explore its feasibility and accuracy. METHODS: A total of 21 cases with distal femoral fractures admitted into the Department of Orthopedics, Affiliated Hospital of Putian University were included in this study. Dicom format data of lamellar CT scanning was imported into Mimics software for 3D anatomical modeling and virtual fracture reduction. The steel plates was chose from standard parts database for virtual internal fixation, and to design the navigation module with screw. 3D printing skeleton, steel plates, navigation module, internal fixation implants were simulated based on the printed bones model. Locations of steel plates and screws were determined by the navigation module. Then the sticking effects of navigation module, screws position and postoperative appearance were observed. After second CT scan and 3D reconstruction, 3D registration was performed to obtain the data of the three-dimensional coordinate values of screws entrance points and piercing points to analyze the results. RESULTS: A total of 21 plates and 180 screws were placed with the assistance of navigation module. CT scanning and 3D reconstruction was performed in twenty-one cases of postoperative bone model. The position of plates was in high accordance with the digital design by Mimics software. There were no significant differences between spatial location of screw entrance points and piercing points. The real operation was quite consistent with preoperative design. Navigation module and the corresponding distal femur bony structure jointed closely. The sticking effects and stability of navigation module were good, which was able to guide placement of steel plates and screws. CONCLUSION: These methods can enhance the accuracy of internal fixation of the standard parts database steel plate in distal femur fractures, with the assistance of navigation module. PMID- 26875713 TI - [Correlation of pre-operative factors with the outcome of surgical treatment of Hirayama disease]. AB - OBJECTIVE: To investigate the relationship of pre-operative clinical related factors with the outcome of surgical treatment in patients with Hirayama disease. METHODS: A total of 46 consecutive patients with Hirayama disease treated by anterior cervical discectomy decompression and fusion in Peking University Third Hospital from October 2006 to January 2014 were reviewed retrospectively. Odom's criteria was used to evaluate the subjective outcome of surgical treatment. Five pre-operative factors were collected including duration of disease at the time of treatment, age of onset, extremity involvement, gross hand function score and fine hand function score. The correlation between these five clinical related factors and postoperative outcome was evaluated with Logistic regression. The receiver operating characteristic (ROC) curve and area under the ROC curve were used to evaluate the significant result of Logistic regression and the optimal diagnostic value. RESULTS: A total of 40 in 46 (87.0%) patients with complete clinical and radiographic follow-up data were included in this study. The mean follow-up period was 48.6 months (12-98 months). All patients were male. The outcome at the final follow-up according to Odom's criteria was: Excellent 5 cases, Good 21 cases, Fair 14 cases and no Poor case. Only two pre-operative factors, age of onset and gross hand function score, showed statistical correlation with the post-operative outcome assessment by Logistic regression. ROC analysis showed that the area under the ROC curve of age of onset and gross hand function score were 0.790 and 0.793 respectively. The optimal predictive threshold was 15.5 years old and 5.5 points respectively. CONCLUSIONS: Age of onset and gross hand function score were two pre-operative factors correlated with the post-operative outcome. These two factors could be used to predict the outcome of surgical treatment of Hirayama disease preoperatively. PMID- 26875714 TI - [Presence of subclinical inflammation in axial spondyloarthropathy patients in clinical remission]. AB - OBJECTIVE: To investigate the incidence of bone marrow edema in sacroiliac joint under examination of magnetic resonance imaging (MRI) in patients with axial spondyloarthropathy (SpA) in remission. METHODS: A total of 87 patients with axial SpA were recruited. Disease activity was assessed by calculation of BASDAI and ASDAScrp scores. All the SpA patients completed MRI scan of sacroiliac joint and bone marrow edema in sacroiliac joint was quantized by SPARCC scoring standard. RESULTS: According to BASDAI standard (n=87), 60 patients (69.0%) were categorized as remission, of which 40 patients (66.7%) exhibited bone marrow edema in sacroiliac joint (SPARCC>0). 27 patients (31.0%) were categorized as activity, while 23 patients (85.2%) exhibited bone marrow edema in sacroiliac joint (SPARCC>0). According to ASDAScrp standard (n=75), 12 patients (16.0%) were classified as remission, of which 4 patients (33.3%) exhibited bone marrow edema in sacroiliac joint (SPARCC>0). 63 patients (31.0%) were categorized as activity, while 52 patients (82.5%) exhibited bone marrow edema in sacroiliac joint (SPARCC>0). SPARCC score positively correlated with BASDAI (r=0.271, P<0.05), ASDAScrp (r=0.291, P=0.011) and patient global assessment (r=0.414, P<0.01). All the patients were classified as non-regular treatment group, traditional drugs group, and biologics group based on the therapeutic conditions. Percentages of patients with SPARCC>0 in sacroiliac joint were also different among these groups (86.8%, 75.0%, 31.6%, chi(2)=21.483, P<0.01). CONCLUSIONS: About 1/3 to 2/3 axial SpA patients in clinical remission represent bone marrow edema in sacroiliac joint under MRI examination, which indicates presence of subclinical inflammation in axial SpA with clinical remission. SpA patients treated with biologics could have better remission of radiographic inflammation on MRI. PMID- 26875715 TI - [Expression of G-CSF and clinical pathological significance in cervical cancer]. AB - OBJECTIVE: To observe the expression of granulocyte colony-stimulating factor (G CSF) in cervical cancer and to investigate its clinical significance. METHODS: A total of 53 cases of cervical cancer with a large number of granular cell infiltration were collected in the last ten years, and 57 cases of cervical cancer with no cell infiltration were selected as controls. The infiltration of neutrophils in cancer tissues was observed, and the expression of G-CSF in cancer tissue was detected by immunohistochemistry at the same time. And the relationship between the expression of G-CSF and clinical pathological significance in cervical cancer was analyzed. All the patients were followed up, and the effect of G-CSF on the prognosis of the patients was analyzed. RESULTS: Expression of G-CSF was observed in 53 cases out of the 110 cases cervical cancer. Among them, 48 (90.6%) cases were squamous cell carcinoma, 5(9.4%) cases were adenocarcinoma. The expression of G-CSF was closely related to granulocyte infiltration, histological type, necrosis, high grading and regional lymph node metastasis (P<0.01), but not related to size of tumor (P>0.05). G-CSF positive cases were 33.676 and 78.495 times more dangerous than those cases that were negative in high grading and regional lymph node metastasis (P<0.01). The difference in survival between the positive and the negative was also significant (P<0.01). CONCLUSIONS: Certain cervical cancer can produce G-CSF, and the most common in non-keratinizing squamous cell carcinoma. Cervical cancer tissue that excretes G-CSF tends to have low differentiation, obvious dysplasia, high degree of malignancy, extensive necrosis and granulocyte cell infiltration, and is often associated with lymph node metastasis, with low survival rate and poor prognosis. PMID- 26875716 TI - [Clinical analysis of microsurgical treatment of giant intracranial arteriovenous malformations]. AB - OBJECTIVE: To explore the clinical features and microsurgical treatment strategies of giant intracranial arteriovenous malformations (AVM). METHODS: A total of 15 cases of giant intracranial AVM treated with microsurgery were analyzed retrospectively. According to the Spetzler-Martin grade, there were 4 cases of grade IV, 11 cases of grade V. Pre-operative endovascular embolizations were carried out in 3 AVMs. RESULTS: All the included patients were confirmed as giant intracranial AVM by magnetic resonance angiography (MRA), digital subtraction angiography (DSA), 3-dimensional CT angiography (3D-CTA) before surgery. All the resected tissues were sent for pathological examination, and the diagnoses were confirmed as AVM. The average operation time of the 15 patients was 10.3 +/-6.9 hours. After 1-3 months, all the patients were rechecked by DSA, the large vascular malformations in 12 cases were completely resected, 3 cases had a small amount of residual further treated with gamma knife treatment. Magnetic resonance imaging (MRI) and MRA examination indicated that the residual AVM was occluded after 12 months. Patients were followed up at 6, 12 and 24 months after operation, and assessed by Glasgow outcome scale (GOS) score: 13 cases good, 1 cases mild disability, 1 cases severe disability; the good rate was 86.6%, with no dead case. CONCLUSION: Sufficiently preoperative preparation, appropriate operative methods and skills are necessary to treat giant intracranial arteriovenous malformation. PMID- 26875717 TI - [Study based on sonoelastography technology for spastic gastrocnemius in rat with spinal cord injure]. AB - OBJECTIVE: To investigate the pathological characteristic of gastrocnemius (GM) and quantitatively assess GM tissue stiffness in spinal cord injury (SCI) rat models; to explore the novel method in evaluation of GM stiffness. METHODS: A total of 54 SD male rats (weight 260-280 g) were allocated into normal control group (0 w) and model groups (2, 4, 8 and 12 w) in this study. Complete SCI (T10 level) was applied in model groups. At the above different time points, Modified Ashworth Scale (MAS) was used to assess the GM spasticity; Basso, Beattie, and Bresnahan Locomotor Rating Scale (BBB) was used to assess the movement ability of lower limb. GM stiffness was assessed with shear wave sonoelastography technology in these groups. All GM at right side of rats was further checked by pathological examinations (muscle weight, ATP staining, myosin heavy chain (MyHC) electrophoretic analysis) after sonoelastography imaging examinations. RESULTS: After removing the overweight and underweight rat models which were alive, six rats were included in each group. There were some pathologic changes in GM in SCI rat models. Compared with normal control group, data from model groups showed ankle dorsiflexors MAS (1.5+/-0.8-0.8+/-0.7 score) was increased (P<=0.05), BBB scores of lower limb (3.2+/-1.0-7.2+/-1.3score) were decreased (P<=0.05). The GM elastic modulus was increased at dorsiflexion location in model group (25.1+/-2.4 37.4+/-5.5 kPa, P<=0.05); GM weights were decreased, ratio of type I fibers was decreased and ratio of type II fibers was increased in GM. Compared with normal control group, MyHC-I was decreased, while MyHC-II was increased according electrophoretic analysis. CONCLUSIONS: Both pathological characteristic and muscle stiffness of GM change after SCI. Shear-wave sonoelastography technology can be used to assess the GM stiffness in SCI rat models. PMID- 26875718 TI - [Oncolytic property of HSV-1 recombinant viruses carrying the p53 gene]. AB - OBJECTIVE: To obtain the recombinant herpes simplex virus 1 (HSV-1) inserted p53 gene with homologous recombination technology and investigate the virus' replication ability and oncolytic property in vitro and in vivo. METHODS: A eukaryotic expression case with p53 gene was cloned into pKO5/BN. The pKO5/p53 was constructed and transfected to the E. coli with pHSVDeltaIR-BAC by electroporation. Then the recombinant pHSVDeltaIR-BAC/p53 was obtained and transfected into Vero cells. Recombinant virus (MH1004) was identified by Southern blot and Western blot. Then the virus' replication abilities in several human tumors cells were tested by plaque assay. A murine melanoma model was established by subcutaneous inoculation of B16 cells. A dosage of 2*10(6) PFU (plaque forming unit) of MH1004, MH1001, HSV-1 wt or PBS was injected 3 times intratumorally in every 3 days. The tumor volume and survival rate were measured twice a week. RESULTS: The results of Western blot showed that the p53 protein can be detected from the Vero cells infected by MH1004. The replication abilities of MH1004 and HSV-1 wt in the same tumor cell was insignificant (P>0.05). And MH1004's replication abilities in SK-N-SH and U251 was significantly higher than other cancer cells. The tumors volume of group HSV-1 wt, MH1001(HSVDeltaIR)and MH1004 were (6 180+/-751), (5 760+/-267) and (4 850+/-532) mm(3) compared with PBS group (9 860+/-91) mm(3,) the difference of reduction of tumors volume was significant (P< 0.01). And the tumors volume of MH1004 group was smaller than HSV 1 wt and MH1001 group, but without significant difference (P>0.05). And the survival rate of MH1004 treated mice (5/6) was greatly higher than PBS (3/6), HSV 1 wt (3/6) and MH1001 (3/6). CONCLUSION: The replication abilities of MH1004 in neural tumor are very high and MH1004 can inhibit the growth of tumor so that prolong the survival of mice bearing murine melanoma. PMID- 26875719 TI - [Expression and significance of AKT/mTOR signaling pathway in natural degeneration in vitro model of endplate chondrocytes of rats]. AB - OBJECTIVE: To investigate the expression and significance of AKT/mTOR signaling pathway in natural degeneration in vitro model of rat endplate chondrocytes. METHODS: Rat endplate chondrocytes were isolated and cultured, and the natural degeneration in vitro model of rat endplate chondrocytes was established. The endplate chondrocytes were divided into blank control group (P2 cells), natural degeneration passage group (P5 cells), AKT/mTOR signaling pathway inhibitor group (P5 cells), AKT/mTOR signaling pathway agonist group (P5 cells). The endplate chondrocyte morphology changes were observed under inverted microscope; Toluidine blue staining was used to detect the expression changes of proteoglycans in endplate chondrocytes; Western blot was used to detect the expression changes of AKT and P-AKT; real-time polymerase chain reaction was used to detect the expression of type II collagen, proteoglycan, SOX9 and the key gene of AKT/mTOR signaling pathway, mTOR gene. RESULTS: With in vitro passage of rat endplate chondrocytes, phenotypes of rat endplate chondrocytes gradually reduced or even lost; the type II collagen (P5/P2=0.28, P=0.042 7), proteoglycan (P5/P2=0.33, P=0.026 3), SOX9 (P5/P2=0.40, P=0.018 2) and mTOR (P5/P2=0.28, P=0.038 1) expression were significantly reduced in natural degeneration passage group; in AKT/mTOR signaling pathway inhibitor group: type II collagen (P5/P2=0.19, P=0.034 7), proteoglycan (P5/P2=0.25, P=0.023), SOX9 (P5/P2=0.31, P=0.034 2) and mTOR (P5/P2=0.20, P=0.024 1) expression were decreased compared with natural passage group; in AKT/mTOR signaling pathway agonist group: type II collagen (P5/P2=0.41, P=0.044 1), proteoglycan (P5/P2=0.53, P=0.015 1), SOX9 (P5/P2=0.61, P=0.019 7) and mTOR (P5/P2=0.41, P=0.038 1) expression were increased compared with natural passage group and inhibitor group. CONCLUSION: AKT/mTOR signaling pathway may play an important role in the degenerative process of rat endplate chondrocytes in vitro, artificial control or intervention of AKT/mTOR signaling pathway may accelerate, inhibit or slow the degeneration of endplate cartilage of rats. PMID- 26875720 TI - [Effects of GABAB receptor expression level on cognitive impairment and Arc/Arg3.1 expression in induced epileptic rats model]. AB - OBJECTIVE: To investigate the effects of GABAB receptor on cognitive impairment by using pilocarpine induced kindled rats model and also to check early gene (Arc/Arg3.1) expression. METHODS: Pilocarpine induced kindled rats were divided into four groups (Group normal, Baclofen, CGP and Kindled) randomly, and every group included 20 rats.We checked their cognitive impairment by using passive avoidance test and water maze test.The expression of GABAB receptor (GB1, GB2) and Arc/Arg3.1 was tested by immunohistochemical staining, RT-PCR and Western blot. RESULTS: Passive avoidance test showed four Group rats shuttle times were 6.8+/-0.6, 1.2+/-0.2, 5.4+/-0.5, 3.6+/-0.3, incubation period were 26.1+/-3.9, 152.2+/-12.9, 65.8+/-7.0, 91.2+/-9.1, and water maze test had the same trend, with values in epilepsy groups significantly lower than the normal group of rats, which meant cognitive dysfunction.The above results also showed Baclofen further inhibited the learning and memory ability of the rats and CGP35348 promoted the learning and memory ability.The results of the Arc/Arg3.1 and GB1, GB2 level detection showed that epilepsy groups had significantly higher expression levels of Arc/Arg3.1 and GB1, GB2 than the normal group.Comparison among epilepsy groups showed that Baclofen group expressed lower levels of Arc/Arg3.1 and expressed higher levels of GB1, GB2, however CGP35348 group expressed higher levels of Arc/Arg3.1 and expressed lower levels of GB1, GB2. CONCLUSIONS: GABAB receptor can affect the ability of spatial learning and memory of epileptic rats by regulating Arc/Arg3.1. PMID- 26875721 TI - [The technique of hearing reconstruction in the cases of conductive hearing loss with malformed tympanic segment of facial nerve]. AB - OBJECTIVE: To explore the technique of hearing reconstruction in the cases of conductive hearing loss with malformed tympanic segment of facial nerve. METHODS: Data of 10 cases from July 2010 to March 2015 were collected.The status of tympanic segment of facial nerve, malformed ossicles and the reconstructed methods of ossicular chain were analyzed and discussed based on the embryo anatomy and surgical technique. RESULTS: All facial nerves in 10 cases were exposed and drooping to stapes or cover the oval window.Three patients who had normal stapes, pushed by the exposed facial nerve, were reconstructed with partial ossicular replacement prostheses (PORP). Two patients who had footplate, with partial fixation, were reconstructed with total ossicular replacement prostheses (TORP). Three patients who had atresia of the oval window were implanted with Piston after being made hole in the atresia plate.Another two cases who had atresia of the oval window were implanted with TORP after promontory being drilled out.All cases had no injury of facial nerve and nervous hearing, and no tinnitus.Nine cases had conductive hearing improvement, except one with promontory drilled out. CONCLUSIONS: Patients who had conductive hearing loss with malformed tympanic segment of facial nerve can be treated by the technique of hearing reconstruction.The fenestration technique in the bottom of the scala tympani of the basal turn provides us a new method for treating patients whose oval window was fully covered by malformed facial nerve. PMID- 26875722 TI - Dual neurocircuitry dysfunctions in disruptive behavior disorders: emotional responding and response inhibition. AB - BACKGROUND: To determine the functional integrity of the neural systems involved in emotional responding/regulation and response control/inhibition in youth (age 10-18 years) with disruptive behavioral disorders (DBDs: conduct disorder and/or oppositional defiant disorder) as a function of callous-unemotional (CU) traits. METHOD: Twenty-eight healthy youths and 35 youths with DBD [high CU (HCU), n = 18; low CU (LCU), n = 17] performed the fMRI Affective Stroop task. Participants viewed positive, neutral, and negative images under varying levels of cognitive load. A 3-way ANOVA (group*emotion by task) was conducted on the BOLD response data. RESULTS: Youth with DBD-HCU showed significantly less activation of ventromedial prefrontal cortex (vmPFC) and amygdala in response to negative stimuli, compared to healthy youth and youth with DBD-LCU. vmPFC responsiveness was inversely related to CU symptoms in DBD. Youth with DBD-LCU showed decreased functional connectivity between amygdala and regions including inferior frontal gyrus in response to emotional stimuli. Youth with DBD (LCU and HCU) additionally showed decreased insula responsiveness to high load (incongruent trials) compared to healthy youth. Insula responsiveness was inversely related to ADHD symptoms in DBD. CONCLUSIONS: These data reveal two forms of pathophysiology in DBD. One associated with reduced amygdala and vmPFC responses to negative stimuli and related to increased CU traits. Another associated with reduced insula responses during high load task trials and related to ADHD symptoms. Appropriate treatment will need to be individualized according to the patient's specific pathophysiology. PMID- 26875723 TI - Retinal pigment epithelial cell multinucleation in the aging eye - a mechanism to repair damage and maintain homoeostasis. AB - Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Dysfunction or death of RPE cells underlies many age-related retinal degenerative disorders particularly age-related macular degeneration. During aging RPE cells decline in number, suggesting an age-dependent cell loss. RPE cells are considered to be postmitotic, and how they repair damage during aging remains poorly defined. We show that RPE cells increase in size and become multinucleate during aging in C57BL/6J mice. Multinucleation appeared not to be due to cell fusion, but to incomplete cell division, that is failure of cytokinesis. Interestingly, the phagocytic activity of multinucleate RPE cells was not different from that of mononuclear RPE cells. Furthermore, exposure of RPE cells in vitro to photoreceptor outer segment (POS), particularly oxidized POS, dose-dependently promoted multinucleation and suppressed cell proliferation. Both failure of cytokinesis and suppression of proliferation required contact with POS. Exposure to POS also induced reactive oxygen species and DNA oxidation in RPE cells. We propose that RPE cells have the potential to proliferate in vivo and to repair defects in the monolayer. We further propose that the conventionally accepted 'postmitotic' status of RPE cells is due to a modified form of contact inhibition mediated by POS and that RPE cells are released from this state when contact with POS is lost. This is seen in long-standing rhegmatogenous retinal detachment as overtly proliferating RPE cells (proliferative vitreoretinopathy) and more subtly as multinucleation during normal aging. Age-related oxidative stress may promote failure of cytokinesis and multinucleation in RPE cells. PMID- 26875724 TI - The anorexic voice and severity of eating pathology in anorexia nervosa. AB - OBJECTIVE: Internal "anorexic voices" are commonly described by individuals with eating disorders. This study examines whether the perceived power and nature of that voice are related to eating pathology in anorexia nervosa. METHOD: Sixty three women and one man with an ICD-10 diagnosis of anorexia nervosa participated in this study (mean age = 27.3 years; mean BMI = 16.0). Participants completed questionnaires measuring severity of eating pathology, perceived voice power, and beliefs about voices, either at the start or during treatment. RESULTS: A more powerful anorexic voice was associated with more negative eating attitudes in this clinical group. However, BMI was related to a moderating effect, with the interaction of greater voice power and malevolence being associated with a lower BMI. DISCUSSION: These findings suggest the anorexic voice may function as a maintenance factor in anorexia nervosa. Cognitive models of hearing voices may be applicable to disorders other than psychosis. Further explorations are warranted. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:622-625). PMID- 26875725 TI - Visual adaptation provides objective electrophysiological evidence of facial identity discrimination. AB - Discrimination of facial identities is a fundamental function of the human brain that is challenging to examine with macroscopic measurements of neural activity, such as those obtained with functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although visual adaptation or repetition suppression (RS) stimulation paradigms have been successfully implemented to this end with such recording techniques, objective evidence of an identity-specific discrimination response due to adaptation at the level of the visual representation is lacking. Here, we addressed this issue with fast periodic visual stimulation (FPVS) and EEG recording combined with a symmetry/asymmetry adaptation paradigm. Adaptation to one facial identity is induced through repeated presentation of that identity at a rate of 6 images per second (6 Hz) over 10 sec. Subsequently, this identity is presented in alternation with another facial identity (i.e., its anti-face, both faces being equidistant from an average face), producing an identity repetition rate of 3 Hz over a 20 sec testing sequence. A clear EEG response at 3 Hz is observed over the right occipito-temporal (ROT) cortex, indexing discrimination between the two facial identities in the absence of an explicit behavioral discrimination measure. This face identity discrimination occurs immediately after adaptation and disappears rapidly within 20 sec. Importantly, this 3 Hz response is not observed in a control condition without the single-identity 10 sec adaptation period. These results indicate that visual adaptation to a given facial identity produces an objective (i.e., at a pre-defined stimulation frequency) electrophysiological index of visual discrimination between that identity and another, and provides a unique behavior-free quantification of the effect of visual adaptation. PMID- 26875727 TI - Vogt-Koyanagi-Harada disease: Novel insights into pathophysiology, diagnosis and treatment. AB - Vogt-Koyanagi-Harada (VKH) disease is one of the major vision-threatening diseases in certain populations, such as Asians, native Americans, Hispanics and Middle Easterners. It is characterized by bilateral uveitis that is frequently associated with neurological (meningeal), auditory, and integumentary manifestations. Although the etiology and pathogenesis of VKH disease need to be further elucidated, it is widely accepted that the clinical manifestations are caused by an autoimmune response directed against melanin associated antigens in the target organs, i.e. the eye, inner ear, meninges and skin. In the past decades, accumulating evidence has shown that genetic factors, including VKH disease specific risk factors (HLA-DR4) and general risk factors for immune mediated diseases (IL-23R), dysfunction of immune responses, including the innate and adaptive immune system and environmental triggering factors are all involved in the development of VKH disease. Clinically, the criteria of diagnosis for VKH disease have been further improved by the employment of novel imaging techniques for the eye. For the treatment, early and adequate corticosteroids are still the mainstream regime for the disease. However, immunosuppressive and biological agents have shown benefit for the treatment of VKH disease, especially for those patients not responding to corticosteroids. This review is focused on our current knowledge of VKH disease, especially for the diagnosis, pathogenesis (genetic factors and immune mechanisms), ancillary tests and treatment. A better understanding of the role of microbiome composition, genetic basis and ongoing immune processes along with the development of novel biomarkers and objective quantitative assays to monitor intraocular inflammation are needed to improve current management of VKH patients. PMID- 26875726 TI - Post-Transcriptional Mechanisms Regulating Epidermal Stem and Progenitor Cell Self-Renewal and Differentiation. AB - Epidermal stem and progenitor cells exist within the basal layer of the epidermis and serve to replenish the loss of differentiated cells because of normal turnover or injury. Current efforts have focused on elucidating the transcriptional regulation of epidermal stem cell self-renewal and differentiation. However, recent studies have pointed to an emerging and prominent role for post-transcriptional regulation of epidermal cell fate decisions. In this review, we will focus on post-transcriptional mechanisms including noncoding RNAs, RNA binding proteins, and mRNA decay-mediated control of epidermal stem and progenitor cell function in the skin. PMID- 26875728 TI - What do patients need to know? A study to assess patients' satisfaction with information about medicines. AB - OBJECTIVES: This study aimed to determine the information needs and reported adherence of patients prescribed medicines for chronic conditions in those who have received a community pharmacy advanced service and those who have not. METHODS: A questionnaire was constructed using validated tools to measure medication information satisfaction and adherence together with questions eliciting information regarding the use of pharmacy services and demographic characteristics. This questionnaire was distributed from four community pharmacies to a convenience sample of 400 patients as they collected their medicines. Patients were eligible if prescribed more than one regular medicine and attending the pharmacy for longer than 3 months. The questionnaire was returned directly to the university. KEY FINDINGS: Two hundred and thirty-two (58%) questionnaires were returned. All respondents desired further information about their prescribed medicines, particularly about potential medication problems. Dissatisfaction centred on side effects, interactions and certain medicine characteristics such as how long it will take to act. Satisfaction with information about medicines and adherence were significantly greater in a subgroup reporting that they had received an advanced pharmacy service, e.g. medicine use review (MUR). CONCLUSION: Patients who had received an advanced service reported greater adherence and satisfaction with medicine-related information. This was a small, observational study, using a convenience sample of four pharmacies; in order to draw definitive conclusions, a larger study with participants randomised to receive an advanced service is required. PMID- 26875729 TI - Erratum to: Regulating Factors in Acid-Sensing Ion Channel 1a Function. PMID- 26875730 TI - A Pit-1 Binding Site Adjacent to E-box133 in the Rat PRL Promoter is Necessary for Pulsatile Gene Expression Activity. AB - Recent evidence reveals that prolactin gene expression (PRL-GE) in mammotropes occurs in pulses, but the molecular process(es) underlying this phenomenon remains unclear. Earlier, we have identified an E-box (E-box133) in the rat PRL promoter that binds several circadian elements and is critical for this dynamic process. Preliminary analysis revealed a Pit-1 binding site (P2) located immediately adjacent to this E-box133 raising the possibility that some type of functional relationship may exist between these two promoter regions. In this study, using serum shocked GH3 cell culture system to synchronize PRL-GE activity, we determined that Pit-1 gene expression occurred in pulses with time phases similar to that for PRL. Interestingly, EMSA analysis not only confirmed Pit-1 binding to the P2 site, but also revealed an interaction with factor(s) binding to the adjacent E-box133 promoter element. Additionally, down-regulation of Pit-1 by siRNA reduced PRL levels during pulse periods. Thus, using multiple evidences, our results demonstrate clearly that the Pit-1 P2 site is necessary for PRL-GE elaboration. Furthermore, the proximity of this critical Pit-1 binding site (P2) and the E-box133 element coupled with the evidences of a site-to-site protein interactions suggest that the process of PRL-GE pulse activity might involve more dynamic and intricate cross-talks between promoter elements that may span some, or all, of the proximal region of the PRL promoter in driving its pulsatile expression. PMID- 26875731 TI - Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism. AB - Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D (3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B. PMID- 26875732 TI - Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor alpha7 Subunit on Microglia Attenuate Abeta-Induced Neurotoxicity on Neural Stem Cells. AB - beta-Amyloid (Abeta) can stimulate microglia to release a variety of proinflammatory cytokines and induce neurotoxicity. Nicotine has been reported to inhibit TNF-alpha, IL-1, and ROS production in microglia. Mitochondrial permeability transition pore (mPTP) plays an important role in neurotoxicity as well. Here, we investigated whether activating the microglial alpha7-nAChR has a neuroprotective role on neural stem cells (NSCs) and the function of mPTP in NSCs in this process. The expression of alpha7-nAChR in rat NSCs was detected by immunocytochemistry and RT-PCR. The viability of microglia and NSCs was examined by MTT assay. The mitochondrial membrane potential (DeltaPsim) and morphological characteristics of NSCs was measured by JC-1 staining and transmission electron microscopy respectively. The distribution of cytochrome c in the subcellular regions of NSCs was visualized by confocal laser scanning microscopy, and the expression levels of cyclophilin D and cleaved caspase-3 were assayed by western blot. The apoptotic rate of NSCs was measured by flow cytometry. The expression of alpha7-nAChR was detected in microglial cells, but no expression was found in NSCs. The viability of rat microglial cells and NSCs was not affected by reagents or coculture itself. Abeta1-42-mediated microglial activation impaired the morphology and the DeltaPsim of mitochondria of NSCs as well as increased cell apoptosis. However, the damage was attenuated when the alpha7-nAChRs on microglial cells were activated or the mPTPs on NSCs were blocked. Blockade of mPTPs on NSCs and activation of alpha7-nAChRs on microglia exhibit neuroprotective roles in Abeta-induced neurotoxicity of NSCs. PMID- 26875734 TI - Introduction to the Milestones in Autoimmune Bullous Diseases. PMID- 26875733 TI - Diphenyl Diselenide Protects Against Mortality, Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity. AB - Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 umol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure. PMID- 26875735 TI - Autoimmune Bullous Diseases: Historical Perspectives. PMID- 26875736 TI - Clinical and Molecular Characterization of Autoimmune Bullous Diseases. PMID- 26875737 TI - Pathophysiology of Autoimmune Bullous Diseases. PMID- 26875738 TI - Duplicating Autoimmune Bullous Diseases by Passively Transferring Autoantibodies into Animals. PMID- 26875739 TI - The Relationship between Autoimmune Bullous Disease and Systemic Disorders. PMID- 26875740 TI - Epidemiology and Immunogenetics of Autoimmune Bullous Diseases. PMID- 26875741 TI - Xylella fastidiosa Transmission and Life History of Two Cicadellinae Sharpshooters, Kolla paulula and Bothrogonia ferruginea (Hemiptera: Cicadellidae), in Taiwan. AB - Xylella fastidiosa causes Pierce's disease (PD) and is transmitted by xylem-sap feeding insects. While X. fastidiosa-infected grapevines have been detected, the transmission vectors reported have never been recorded in Taiwan. Previous studies have suggested that Kolla paulula (Walker) and Bothrogonia ferruginea (F.) are candidate vectors in Taiwan. Here, we explored the life history of these two leafhoppers, evaluated the transmission efficiency of X. fastidiosa by the vectors, and investigated the genetic identity of three collected X. fastidiosa strains, namely, GMb, BQa, and BQ7f from the grapevine cultivars Golden Muscat (GM) and Black Queen (BQ), and one previously extracted strain GV148 from Kyoho (GV) showing PD symptoms in local vineyards. The results showed that all four strains were 100% identical to X. fastidiosa isolate Temecula1 from a naturally infected grapevine in the United States based on sequence analyses of 16S rRNA and 16S-23S ITS. The acquisition rates by K. paulula and B. ferruginea from the symptomatic cultivar Golden Muscat were 83.3 and 70.0% per individual, and the transmission rates to healthy grapevines were 13.3 and 6.7%, respectively. The acquisition rates by the groups of three K. paulula from the symptomatic cultivars Golden Muscat and Black Queen were 54.7 and 49.6%, respectively. Additionally, the transmission rates by K. paulula from and to each of these two grapevine cultivars were not significantly different. In view of their acquisition from infected grapevines and the effective transmission of X. fastidiosa to healthy grapevines, these two sharpshooter species are vectors of X. fastidiosa in Taiwan. PMID- 26875742 TI - The safety of generic substitution in epilepsy. PMID- 26875743 TI - Generic-to-generic lamotrigine switches in people with epilepsy: the randomised controlled EQUIGEN trial. AB - BACKGROUND: Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. METHODS: The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double blind, crossover study that enrolled adults (aged >=18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200-800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, "high" vs "low"), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80-125%) in the analysis population. This study is registered with ClinicalTrials.gov?, number NCT01713777. FINDINGS: Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98-103, Cmax 90% CI 99-105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. INTERPRETATION: Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. FUNDING: American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration. PMID- 26875744 TI - Single-leaf partial meniscectomy in extensive horizontal tears of the discoid lateral meniscus: Does decreased peripheral meniscal thickness affect outcomes? (Mean four-year follow-up). AB - BACKGROUND: To evaluate whether single-leaf partial meniscectomy in horizontal tears along the entire discoid lateral meniscus has any advantages in clinical and radiological results compared with other meniscectomies in discoid lateral meniscus. METHODS: A total of 145 patients with a horizontal tear pattern in symptomatic lateral discoid meniscus were retrospectively reviewed. Twenty-seven patients had undergone full-extent single-leaf partial meniscectomy (group A), 60 had undergone conventional partial meniscectomy (saucerization) maintaining peripheral meniscal height (group B), and 58 patients had undergone total meniscectomy (group C). Each patient was evaluated with the Lysholm knee score, International Knee Documentation Committee (IKDC) subjective grading, and modified Kellgren-Lawrence grade in plain radiography at their last follow-up. RESULTS: Group C had inferior functional results to groups A and B on the Lysholm knee score and IKDC subjective score. There was no significant difference between groups A and B. Group C fared significantly worse than groups A and B (p=0.003, p<0.001) by modified Kellgren-Lawrence grade. CONCLUSION: With regard to clinical and radiological evaluations in lateral discoid meniscus tears, the full-extent single-leaf partial meniscectomy group had no adverse results compared with the total meniscectomy group and was not significantly different compared to the conventional partial meniscectomy group. STUDY DESIGN: Cohort study. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID- 26875745 TI - Repairable Woven Carbon Fiber Composites with Full Recyclability Enabled by Malleable Polyimine Networks. AB - Carbon-fiber reinforced composites are prepared using catalyst-free malleable polyimine networks as binders. An energy neutral closed-loop recycling process has been developed, enabling recovery of 100% of the imine components and carbon fibers in their original form. Polyimine films made using >21% recycled content exhibit no loss of mechanical performance, therefore indicating all of the thermoset composite material can be recycled and reused for the same purpose. PMID- 26875746 TI - Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions. AB - BACKGROUND: Partial DiGeorge syndrome (pDGS) is caused by deletion of the 22q11.2 region. Within this region lies CrK-like (CRKL), a gene encoding an adapter protein belonging to the Crk family that is involved in the signaling cascade of IL-2, stromal cell-derived factor 1alpha, and type I interferon. Although recurrent infections can be observed in patients with deletion of chromosome 22 syndrome, the immune pathogenesis of this condition is yet not fully understood. OBJECTIVE: We aimed to investigate the role of CRKL in T-cell functional responses in patients affected with pDGS. METHODS: Protein expression levels and phosphorylation of CRKL were evaluated in patients with pDGS. T-cell functional assays in vitro and gene-silencing experiments were also performed. RESULTS: CRKL protein expression, as well as its phosphorylation, were reduced in all patients with pDGS, especially on IL-2 stimulation. Moreover, T cells presented impaired proliferation and reduced IL-2 production on anti-CD3/CD28 stimulation and decreased c-Fos expression. Finally, CRKL silencing in Jurkat T cells resulted in impaired T-cell proliferation and reduced c-Fos expression. CONCLUSIONS: The impaired T-cell proliferation and reduction of CRKL, phosphorylated CRKL, and c Fos levels suggest a possible role of CRKL in functional deficiencies of T cells in patients with pDGS. PMID- 26875747 TI - Impact of transcatheter aortic valve implantation on left atrial appendage flow velocities. AB - PURPOSE: Left atrial appendage (LAA) flow velocity has not been extensively studied in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the impact of TAVI on LAA flow velocity. METHODS: Medical records of consecutive TAVI recipients were reviewed retrospectively. Patients with persistent atrial fibrillation were excluded. LAA velocities were measured before and after TAVI by transesophageal echocardiography. RESULTS: Sixty-one patients were included. Mean LAA emptying (EV) and filling (FV) flow velocity before TAVI were 33 +/- 16 cm/s and 31 +/- 14 cm/s, respectively. They increased to 37 +/- 20 (p = 0.0036) and 33 +/- 13 cm/s (p = 0.047) after TAVI in the whole population sample, but not in patients with normal flow AS. In low-flow, low-gradient (LFLG) AS patients, EV and FV increased from 36 +/- 22 to 47 +/- 30 cm/s (p < 0.01), and from 29 +/- 12 to 40 +/- 15 cm/s (p < 0.01), respectively, after TAVI. There was no difference between normal flow and LFLG AS patients in the number of patients who achieved EV >= 40 cm/s post-TAVI (35% versus 47%, p = 0.54, respectively). CONCLUSIONS: LAA EV and FV were low prior to TAVI and increased significantly after TAVI only in patients with LFLG AS. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:375-382, 2016. PMID- 26875748 TI - Comprehensive detection of bacterial carbohydrate-active enzyme coding genes expressed in cow rumen. AB - To find the abundant and characteristic fibrolytic enzyme-coding gene expressed in fiber-associating microbiota, a metatranscriptomic data set was obtained from fiber-associating microbiota, and it was compared with that of rumen fluid floating microbiota and two metagenomic data sets. Fibrolytic rumen bacteria associate with plant polysaccharide and hydrolyze it in the rumen. We obtained a metatranscriptomic assembly from fiber-associating microbiota in three ruminally fistulated Holstein cows fed timothy (Phleum pratense) hay. Each metatranscriptomic data set involved over a thousand of the glycoside hydrolase (GH) gene transcripts that accounted for about 1% of total protein coding gene transcripts. Three-quarters of the total GH gene transcripts were dominated by non-structural oligosaccharide-acting hydrolase gene transcripts. In the fiber associating microbiota, endo-cellulase coding gene families, especially GHs 9 and 5, were abundantly detected, and GHs 9, 11, 30 and 43, carbohydrate esterase 8 and carbohydrate-binding module 6 were characteristically detected. Most fibrolytic gene transcripts assigned to Fibrobacter succinogenes were detected in fiber-associating sections, and GHs 45, 44, 74, 11, 30 and 16 were Fibrobacter characteristically detected. The metatranscriptomic assembly highlighted the characteristic fibrolytic enzymes expressed in the fiber-associated rumen microbiota and offered access to the fibrolytic activities in each fibrolytic bacteria. PMID- 26875749 TI - Investigation of mental health in Indonesian health workers immigrating to Japan under the Economic Partnership Agreement. AB - The aim of this study was to assess the mental health status of Indonesian nurses and care workers who immigrated to Japan after the Economic Partnership Agreement was signed by the governments of Japan and Indonesia in 2008. From November 2012 to March 2013, questionnaires were mailed to 206 workers in 87 medical and caregiving facilities that openly accept Indonesian EPA immigrant workers. Responses were received from 71 workers in 35 facilities. Responses from 22.5% of workers suggested that they were at risk of developing mental health problems, and "gender" and "acquisition state of national qualifications" were the main factors influencing their mental health status. The results suggest that support after obtaining national qualifications is inadequate and that mid and long-term support systems that focus on the needs of immigrant healthcare workers after passing national examinations are necessary. PMID- 26875750 TI - Succession of lignocellulolytic bacterial consortia bred anaerobically from lake sediment. AB - Anaerobic bacteria degrade lignocellulose in various anoxic and organically rich environments, often in a syntrophic process. Anaerobic enrichments of bacterial communities on a recalcitrant lignocellulose source were studied combining polymerase chain reaction-denaturing gradient gel electrophoresis, amplicon sequencing of the 16S rRNA gene and culturing. Three consortia were constructed using the microbiota of lake sediment as the starting inoculum and untreated switchgrass (Panicum virgatum) (acid or heat) or treated (with either acid or heat) as the sole source of carbonaceous compounds. Additionally, nitrate was used in order to limit sulfate reduction and methanogenesis. Bacterial growth took place, as evidenced from 3 to 4 log unit increases in the 16S rRNA gene copy numbers as well as direct cell counts through three transfers on cleaned and reused substrate placed in fresh mineral medium. After 2 days, Aeromonas bestiarum-like organisms dominated the enrichments, irrespective of the substrate type. One month later, each substrate revealed major enrichments of organisms affiliated with different species of Clostridium. Moreover, only the heat-treated substrate selected Dysgonomonas capnocytophagoides-affiliated bacteria (Bacteroidetes). Towards the end of the experiment, members of the Proteobacteria (Aeromonas, Rhizobium and/or Serratia) became dominant in all three types of substrates. A total of 160 strains was isolated from the enrichments. Most of the strains tested (78%) were able to grow anaerobically on carboxymethyl cellulose and xylan. The final consortia yield attractive biological tools for the depolymerization of recalcitrant lignocellulosic materials and are proposed for the production of precursors of biofuels. PMID- 26875751 TI - The Presence of a Reticulated Trabecula-Like Structure Increases the Risk for the Recurrence of Primary Spontaneous Pneumothorax after Thoracoscopic Bullectomy. AB - INTRODUCTION: Deteriorated alveolar structure at the base of blebs and bullae is known as the reticulated trabecula-like structure. Its clinical significance in primary spontaneous pneumothorax (PSP) remains unclear. This study aimed to investigate the impact of the structure on recurrence of PSP after video-assisted thoracoscopic surgery (VATS) bullectomy. METHODS: Between April 2010 and March 2014, 80 cases of PSP in 76 patients who underwent VATS bullectomy using endoscopic staplers were included. The staple line was covered with polyglycolic acid sheets and fibrin glue. Cases were assigned to a normal alveolar structure (NAS) group (n = 54) and a reticulated trabecula-like structure (RT) group (n = 26) based on the histological analysis. Factors associated with recurrence were analysed using logistic regression. RESULTS: The reticulated trabecula-like structure was significantly related to apical lung blebs. The recurrence rate of PSP was significantly higher in the RT group than in the NAS group (38.5% vs. 3.7%; P <0.001). On multivariate analysis, the reticulated trabecula-like structure was an independent factor for recurrence of PSP after VATS bullectomy. CONCLUSION: The change of alveolar structure at the base of apical lung blebs would increase the risk for recurrence of PSP after VATS bullectomy. PMID- 26875752 TI - Brazilian immigrants' oral health literacy and participation in oral health care in Canada. AB - BACKGROUND: Inadequate functional health literacy is a common problem in immigrant populations. The aim of this study was to investigate the association between oral (dental) health literacy (OHL) and participation in oral health care among Brazilian immigrants in Toronto, Ontario, Canada. METHODS: The study used a cross-sectional design and a convenience sample of 101 Brazilian immigrants selected through the snowball sampling technique. Data were analyzed using descriptive statistics and logistic regression modeling. RESULTS: Most of the sample had adequate OHL (83.1 %). Inadequate/marginal OHL was associated with not visiting a dentist in the preceding year (OR = 3.61; p = 0.04), not having a dentist as the primary source of dental information (OR = 5.55; p < 0.01), and not participating in shared dental treatment decision making (OR = 1.06; p = 0.05; OHL as a continuous variable) in multivariate logistic regressions controlling for covariates. A low average annual family income was associated with two indicators of poor participation in oral health care (i.e., not having visited a dentist in the previous year, and not having a dentist as regular source of dental information). CONCLUSION: Limited OHL was linked to lower participation in the oral health care system and with barriers to using dental services among a sample of Brazilian immigrants. More effective knowledge transfer will be required to help specific groups of immigrants to better navigate the Canadian dental care system. PMID- 26875753 TI - Liver failure secondary to poisoning by a homemade product made of star and green anise in a 4-month-old infant. AB - Intoxications in pediatric age represent a frequent cause of visit to the hospital emergency unit. Herb-made products can be toxic for the infant. The neurotoxic properties of the star anise (Illicium verum) have been widely described, although it is a classic product used to treat the infantile colic. Hepatic failure due to the consumption of anise herb elaborated infusions is presented as an exceptional finding in our environment. A case of a 4-month-old infant with hypertransaminasemia, severe coagulopathy, non ketotic hypoglycemia, moderated metabolic acidosis and neurologic symptoms such as seizures and nistagmus is described. After discarding infectious, metabolic and autoimmune etiology and through a meticulous anamnesis, the family referred having administered in the last two months a daily star anise and green anise (Pimpinella anisum) infusion to the patient. It is important to emphasize the serious risk of administering homemade herb infusions to infants. PMID- 26875754 TI - Implementation and validation of an economic module in the Be-FAST model to predict costs generated by livestock disease epidemics: Application to classical swine fever epidemics in Spain. AB - Be-FAST is a computer program based on a time-spatial stochastic spread mathematical model for studying the transmission of infectious livestock diseases within and between farms. The present work describes a new module integrated into Be-FAST to model the economic consequences of the spreading of classical swine fever (CSF) and other infectious livestock diseases within and between farms. CSF is financially one of the most damaging diseases in the swine industry worldwide. Specifically in Spain, the economic costs in the two last CSF epidemics (1997 and 2001) reached jointly more than 108 million euros. The present analysis suggests that severe CSF epidemics are associated with significant economic costs, approximately 80% of which are related to animal culling. Direct costs associated with control measures are strongly associated with the number of infected farms, while indirect costs are more strongly associated with epidemic duration. The economic model has been validated with economic information around the last outbreaks in Spain. These results suggest that our economic module may be useful for analysing and predicting economic consequences of livestock disease epidemics. PMID- 26875755 TI - Strain dependency of the effects of nicotine and mecamylamine in a rat model of attention. AB - RATIONALE: Processes of attention have a heritable component, suggesting that genetic predispositions may predict variability in the response to attention enhancing drugs. Among lead compounds with attention-enhancing properties are nicotinic acetylcholine receptor (nAChR) agonists. OBJECTIVES: This study aims to test, by comparing three rat strains, whether genotype may influence the sensitivity to nicotine in the 5-choice serial reaction time task (5-CSRTT), a rodent model of attention. METHODS: Strains tested were Long Evans (LE), Sprague Dawley (SD), and Wistar rats. The 5-CSRTT requires responses to light stimuli presented randomly in one of five locations. The effect of interest was an increased percentage of responses in the correct location (accuracy), the strongest indicator of improved attention. RESULTS: Nicotine (0.05-0.2 mg/kg s.c.) reduced omission errors and response latency and increased anticipatory responding in all strains. In contrast, nicotine dose-dependently increased accuracy in Wistar rats only. The nAChR antagonist mecamylamine (0.75-3 mg/kg s.c.) increased omissions, slowed responses, and reduced anticipatory responding in all strains. There were no effects on accuracy, which was surprising giving the clear improvement with nicotine in the Wistar group. CONCLUSIONS: The findings suggest strain differences in the attention-enhancing effects of nicotine, which would indicate that genetic predispositions predict variability in the efficacy of nAChR compounds for enhancing attention. The absence of effect of mecamylamine on response accuracy may suggest a contribution of nAChR desensitization to the attention-enhancing effects of nicotine. PMID- 26875756 TI - Delta(9)-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids in mice and rats. AB - RATIONALE: Novel cannabinoid compounds continue to be marketed as "legal" marijuana substitutes, even though little is known about their molecular and behavioral effects. OBJECTIVES: Six of these compounds (ADBICA, ADB-PINACA, THJ 2201, RCS-4, JWH-122, JWH-210) were tested for in vitro and in vivo cannabinoid like effects to determine their abuse liability. METHODS: Binding to and functional activity at CB1 cannabinoid receptors was tested. Locomotor activity in mice was tested to screen for behavioral activity and to identify behaviorally active dose ranges and times of peak effect. Discriminative stimulus effects of the six compounds were tested in rats trained to discriminate Delta(9) tetrahydrocannabinol (Delta(9)-THC). RESULTS: ADBICA, ADB-PINACA, THJ-2201, RCS 4, JWH-122, and JWH-210 showed high affinity binding at the CB1 receptor at nanomolar affinities (0.59 to 22.5 nM), and all acted as full agonists with nanomolar potencies (0.024 to 111 nM) when compared to the CB1 receptor full agonist CP 55940. All compounds depressed locomotor activity below 50 % of vehicle responding, with depressant effects lasting 1.5 to nearly 4 h. All compounds fully substituted (<80 % Delta(9)-THC-appropriate responding) for the discriminative stimulus effects of Delta(9)-THC. 3,4-Methylenedioxy methamphetamine (MDMA) was tested as a negative control and did not substitute for Delta(9)-THC (11 % Delta(9)-THC-appropriate responding). CONCLUSIONS: All six of the compounds acted at the CB1 receptor and produced behavioral effects common to abused cannabinoid compounds, which suggest that these compounds have substantial abuse liability common to controlled synthetic cannabinoid compounds. PMID- 26875757 TI - Smoke and mirrors: The overnight abstinence paradigm as an index of disrupted cognitive function. AB - RATIONALE: Smoking abstinence is known to cause decrements in cognition, but the effects are small and variable. One way to reduce variance may be to aggregate measures or visits. Although trait-like individual differences in smoking abstinence effects on cognition are theorized to predict relapse, the test-retest reliability (TRR) assumed in trait models has not been evaluated. OBJECTIVES: The objectives of this study were to assess the value of aggregating measures to determine effect sizes (ESs) of smoking versus abstinence on measures of cognition and to assess the short-term TRR of abstinence effects on cognition. METHODS: Thirty adult smokers completed the typical overnight abstinence paradigm twice; each visit pair consisted of one smoking visit and one abstinent visit. Measures of attention, working memory, and inhibitory control were obtained in each visit. RESULTS: There were small to medium ESs for smoking abstinence on individual cognitive measures during the first abstinence experience ("visit pair"). Aggregating the measures within the visit pair and across visit pairs additively increased the ES of smoking versus abstinence. Although TRRs were acceptable between smoking visits and between abstinent visits, TRRs for abstinence effects (smoking vs. abstinent visit differences) on cognition were consistently weak. DISCUSSION: The ability of the typical overnight abstinence paradigm to reflect disrupted cognition at the group level can be substantially improved by aggregating across cognitive outcomes and/or multiple study visits. However, the patterns of poor TRR of smoking-abstinence differences in cognition caution against their use as trait-like markers in studies of relapse or treatment response. PMID- 26875758 TI - Interobserver Variability of Ki-67 Measurement in Breast Cancer. AB - BACKGROUND: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. METHODS: Thirty observers from thirty different institutions reviewed Ki-67-stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA) by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method) and categorical estimation. Intraclass correlation coefficient (ICC) of Ki-67 index was calculated for comparative analysis. RESULTS: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858). The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874). In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895). In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. CONCLUSIONS: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability. PMID- 26875759 TI - Prognostic Implication of Semi-quantitative Immunohistochemical Assessment of CD20 Expression in Diffuse Large B-Cell Lymphoma. AB - BACKGROUND: Immunohistochemical demonstration of CD20 in diffuse large B-cell lymphoma (DLBCL) is prerequisite not only for the diagnosis but also for assigning patients to rituximab-containing chemotherapy. However, little is known about the impact of abundance of CD20 expression assessed by immunohistochemistry on the clinical outcome of DLBCL. We performed a semi-quantitative immunohistochemical analysis of CD20 expression in DLBCL to examine the prognostic implication of the level of CD20 expression. METHODS: Pre-treatment diagnostic tissue samples from 48 DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen were represented in a tissue microarray and immunostained for CD20. The relative abundance of CD20 expression was semi-quantitatively scored using a web-based ImmunoMembrane plug-in. Receiver operating characteristic curve analysis was used to determine a prognostically relevant cut-off score in order to dichotomize the patients into CD20-high versus CD20-low groups. RESULTS: The levels of CD20 expression were heterogeneous among the patients, with a wide and linear distribution of scores. Patients in CD20-low group showed significantly poor clinical outcome. CONCLUSIONS: The levels of CD20 expression in DLBCL are heterogeneous among the patients with DLBCL. A subgroup of the patients with CD20 expression levels below the cut-off score showed poor clinical outcome. PMID- 26875760 TI - Morphologic Analysis of Cytomegalovirus Infected Cells in Bronchial Washing Cytology: Comparison of Liquid-Based Preparation and Conventional Smear. AB - BACKGROUND: The cytopathic effects of cytomegalovirus (CMV) infection have been well described since the virus was first reported; however, the morphology of CMV infection has not been clearly studied. We examined the difference in detailed cytologic findings in bronchial washing cytology between liquid-based and conventionally prepared smears. METHODS: Bronchial washing cytology was processed using either the conventional preparation (CP) or liquid-based preparation (LBP). Sixty-nine cells with typical cytopathic effects of CMV infection were detected on CP slides and 18 cells on LBP slides. Using the image analyzer, area, circumference, major axis, and minor axis of the cytoplasm, nucleus, and intranuclear inclusion were measured in singly scattered CMV-infected cells, and histiocytes were used as a control. RESULTS: The mean cytoplasmic area of CMV infected cells was 1.47 times larger than that of histiocytes in CP and 2.92 times larger in LBP (p<.05). The mean nuclear area of CMV-infected cells was 2.61 times larger than that of histiocytes in CP and 4.25 times larger in LBP (p<.05). The nucleus to cytoplasm ratio and intranuclear inclusion to cytoplasm ratio of the mean area, circumference, major axis, and minor axis in CP were larger than those in LBP (p<.05). CONCLUSIONS: The sizes of cytoplasm, nucleus, and intranuclear inclusion were larger in LBP than in CP, indicating that CMV infected cells are easily detectable in LBP. However, the nucleus-to-cytoplasm ratio was larger in CP, suggesting that differentiation from malignancy or regenerative atypia requires caution in CP. PMID- 26875761 TI - Phleboviruses associated with sand flies in arid bio-geographical areas of Central Tunisia. AB - An entomological investigation was carried out in 2014 at two sites located in Central Tunisia, one irrigated and another non-irrigated situated in arid bio geographical areas. Sand flies of the subgenus Larroussius namely Phlebotomus perfiliewi, Phlebotomus perniciosus, and Phlebotomus longicuspis are the most abundant sand fly species in the irrigated site. However, in the non-irrigated site, Phlebotomus papatasi of the Phlebotomus genus is the most abundant species. A total of 3191 sand flies were collected and pooled with up to 30 specimens per pool based on sex, trapping location and collection date, were tested for the presence of phleboviruses by nested reverse transcriptase polymerase chain reaction in the polymerase gene and sequenced. Of a total of 117 pools, 4 were positive, yielding a minimum infection rate of sand flies with phleboviruses of 0.12%. Phylogenetic analysis performed using partial nucleotide and amino acid sequence in the polymerase gene showed that these phleboviruses belonged to four different clusters corresponding to Toscana virus (TOSV), Saddaguia virus (SADV), Sandfly Fever Sicilian Virus (SFSV) and Utique virus (UTIV). This study provides more evidence that the abundance of P. perfiliewi is associated with the development of irrigation in arid bio-geographical areas of Central Tunisia which may have led to the emergence of phleboviruses. We report the first detection of TOSV from sand flies collected from Central Tunisia. PMID- 26875762 TI - Anti-Leptospira spp. antibodies in Crotalus durissus collilineatus kept in captivity and its zoonotic relevance. AB - Leptospirosis is a worldwide spread zoonosis that can affect all groups of vertebrates, including reptiles. Because it has been little studied in snakes, this study focused on determining the occurrence of anti-Leptospira spp. antibodies in 64 Crotalus durissus collilineatus kept in captivity and on identifying the most common serovars in these animals, using the microscopic agglutination test. Of these, almost 90% were positive and there were reactions to the 22 serovars used in the study. The most common serovar in these snakes was Javanica, Andamana and Patoc. Most frequent titers were 25 and 50, although high titers (such as 1600) were also recorded, despite the absence of clinical symptoms. The possibility should be considered of captive snakes serving as a serious source of leptospiral infection in humans, which is why it is essential to study, prevent and control the disease in breeding centers and serpentariums. PMID- 26875763 TI - Molecular surveillance of antimalarial drug resistance related genes in Plasmodium falciparum isolates from Eritrea. AB - The introduction of artemisinin-based combination therapy has led to extraordinary results in malaria control, however the recent emergence of partial resistance to artemisinin therapy in Southeast Asia jeopardizes these successes. This study aimed at investigating resistance to the antimalarial drugs by evaluating the polymorphisms in the PfK13, Pfcrt and Pfmdr1 genes in Plasmodium falciparum isolates obtained from patients in Eritrea. PMID- 26875764 TI - Spatial spread of dengue in a non-endemic tropical city in northern Argentina. AB - After more than eighty years dengue reemerged in Argentina in 1997. Since then, the largest epidemic in terms of geographical extent, magnitude and mortality, was recorded in 2009. In this report we analyzed the DEN-1 epidemic spread in Oran, a mid-size city in a non-endemic tropical area in Northern Argentina, and its correlation with demographic and socioeconomic factors. Cases were diagnosed by ELISA between January and June 2009. We applied a space-time and spatial scan statistic under a Poisson model. Possible association between dengue incidence and socio-economic variables was studied with the Spearman correlation test. The epidemic started from an imported case from Bolivia and space-time analysis detected two clusters: one on February and other in April (in the south and the northeast of the city respectively) with risk ratios of 25.24 and 4.07 (p<0.01). Subsequent cases spread widely around the city without significant space-temporal clustering. Maximum values of the entomological indices were observed in January, at the beginning of the epidemic (B=21.96; LH=8.39). No statistically significant association between socioeconomic variables and dengue incidence was found but positive correlation between population size and the number of cases (p<0.05) was detected. Two mechanisms may explain the observed pattern of epidemic spread in this non-endemic tropical city: a) Short range dispersal of mosquitoes and people generates clusters of cases and b) long-distance (within the city) human movement contributes to a quasi-random distribution of cases. PMID- 26875765 TI - A novel antimicrobial peptide derived from membrane-proximal external region of human immunodeficiency virus type 1. AB - With increasing microbial drug resistance worldwide, antimicrobial peptides (AMPs) are considered promising alternatives to addressing this problem. In this study, a series of synthetic peptides were designed based on the membrane disrupting properties of the membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) envelope protein. The peptide AP16-A was found to exhibit the most effective antimicrobial activities against both Gram negative and Gram-positive bacteria. The minimal bactericidal concentration (MBC) of AP16-A ranged from 2 MUg/ml to 16 MUg/ml. AP16-A had no detectable cytotoxicity in various tissue cultures and a mouse model. Furthermore, results of confocal fluorescence microscopy and the SYTOX Green uptake assay indicated that AP16-A killed Gram-negative bacteria by the combined effects of relatively slow membrane permeabilization and interaction with an intracellular target, while it killed Gram-positive bacteria by a fast membrane permeabilization process, which achieved relatively more rapid bacterial killing kinetics. The results of this study support the potential use of AP16-A as an AMP. PMID- 26875766 TI - Sesamoid Position in Healthy Volunteers Without Deformity: A Computed Tomography Study. AB - We used coronal computed tomography to determine the normal sesamoid position in 20 healthy volunteers. The sample involved 40 feet (20 left [50%] and 20 right [50%]) in 20 volunteers, including 11 females (55%) and 9 males (45%). The relationship between the first metatarsal head and the sesamoid complex was categorized as Yildirim grade 0 in every case (100%). The mean width of the foot was 77.7 +/- 5.8 mm, and the ratio of the foot width to the distance from the second metatarsal head to the tibial sesamoid was 39.6% +/- 2.02%. Based on our findings, we consider Yildirim grade 0 to be the normal sesamoid alignment. PMID- 26875767 TI - Use of a Proximal Humeral Locking Plate for Complex Ankle and Hindfoot Fusion. AB - Arthrodesis of the ankle and hindfoot in the setting of major deformity is challenging and associated with substantial risks. Patients often have significant comorbidities that lead to unforgiving soft tissues, poor vascularity, and poor bone quality. This creates the high-risk scenario of poor wound healing and poor implant fixation. Complications can be devastating, leading to loss of the limb and sepsis. The use of locking plate technology might provide biomechanical and operative technique advantages in such patients. We retrospectively assessed the results of the modified use of the PHILOS(TM) (Synthes((r)), Zuchwil, Switzerland) proximal humeral locking plate in 21 patients (11 males, 10 females; mean age 56.1 years, range 25 to 74 years) who had undergone complex fusions, including tibiotalar (n = 4), tibiocalcaneal (n = 7), or tibiotalocalcaneal (n =10) fusions. The average follow-up period was 14.6 (median 10, range 6 to 49) months. Of the 21 fusions, 18 achieved union (85.7%) at an average period of 4.8 (median 4.3, range 3 to 12) months. The overall deep infection rate was 14.3%. Overall, 17 of the 21 patients (81%) were satisfied with the result (good to excellent), 1 reported the result was fair (4.8%), and 3 patients developed nonunion and were dissatisfied with the procedure (14.3%). The present study is the largest series to date of patients undergoing complex ankle and hindfoot arthrodesis with the use of a proximal humeral locking plate and confirms previous findings that the technique is reliable with union, satisfaction, and complication rates comparable to those of other techniques. PMID- 26875768 TI - Cement Calcaneoplasty: An Innovative Method for Treating Nonunion in Calcaneal Insufficiency Fracture. AB - Insufficiency type stress fractures are common in older patients with osteoporosis. Persistent pain after nonunion of these fractures can be disabling, with the management options often limited. We aimed to assess the suitability of fluoroscopic-guided injection of bone cement into a persistently symptomatic nonuniting calcaneal insufficiency fracture. To the best of our knowledge, this technique has not previously been described in the published data. After local subcutaneous anesthesia, the midpoint of the fracture site was accessed by trocar insertion under radiographic guidance, and bone cement was injected directly into the site. A preprocedure visual analog scale pain score of 90 of 100 was recorded. This had improved to 0 of 100 at the 12-month follow-up point after the procedure. The aim of the present case report was to raise awareness of percutaneous calcaneoplasty, which we believe to be a safe and well-tolerated technique for the management of osteoporotic insufficiency fracture of the calcaneus. We propose that this technique be considered when conservative methods aimed at promoting fracture healing have failed. PMID- 26875769 TI - Therapeutic antioxidant and anti-inflammatory effects of laser acupuncture on patients with rheumatoid arthritis. AB - BACKGROUND AND OBJECTIVE: The laser acupuncture has many potential therapeutic effects. Currently, they are not evaluated for their therapeutic effects on rheumatoid arthritis (RA) patients. The aim of this study was to investigate the effects of laser acupuncture on the oxidative and antioxidative markers, as well as the inflammatory markers and disease activity of RA patients. DESIGN/MATERIALS AND METHODS: The study was conducted on 30 RA patients and 20 healthy subjects. The patients were subjected to laser acupuncture (904 nm, 100 mW power output, 1 minute irradiation time, beam area of 1 cm(2) , total energy per point 6 J, energy density 6 J/ cm(2) , irradiance 0.1 W/cm(2) , frequency 10000 Hz, duty cycle 100%) for 3 days/week for duration of 4 weeks. The acupuncture points of exposure were LI4, TE5, LI 11, DU 14, LIV3, SP6, GB34, and S36. The levels of oxidative and antioxidant markers were determined by spectrophotometric methods whereas the inflammatory markers were determined by ELISA methods. Lastly, using DAS28 scores the disease activity was assessed. RESULTS: After laser acupuncture, the study group revealed significantly increased plasma superoxide dismutase (SOD), glutathione reductase (GR), catalase activities, blood glutathione (GSH), and plasma ATP concentrations, compared to those before treatment (P < 0.0005). Moreover, the results revealed significantly reduced plasma malondialdehyde (MDA), serum nitrate and nitrite, serum C-reactive protein (CRP), plasma interleukin-6 (IL-6) levels and significantly reduced glutathione peroxidase (GPx) activity and erythrocyte sedimentation rate (ESR) in laser exposed patients, compared to those before treatment (P < 0.0005). The RA patients subjected to laser acupuncture showed highly significant reduction in disease activity (P < 0.0005) based on DAS28 score. CONCLUSION: Our study results confirmed the effectiveness of laser acupuncture in alleviating oxidative stress and inflammation, improving antioxidant and energy metabolic status, while also suppressing the disease activity in RA patients. Laser acupuncture is a promising treatment modality to reduce the pain and suffering of RA patients because of its efficiency in inhibiting most of the main factors involved in the pathogenesis of this disease. Lasers Surg. Med. 48:490-497, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26875770 TI - Mouse macrophage polarity and ROCK1 activity depend on RhoA and non-apoptotic Caspase 3. AB - The macrophages have different subtypes with different functions in immune response and disease. It has been generally accepted that M1 macrophages are responsible for stimulation of immune system and inflammation while M2 macrophages play a role in tissue repair. Irrespective of the type, macrophage functions depend on actin cytoskeleton, which is under the control of small GTPase RhoA pathway and its downstream effector ROCK1. We generated RhoA-deleted macrophages and compared the effect of RhoA deletion on M0, M1 and M2 macrophage phenotype. Our studies showed that, unexpectedly, the RhoA deletion did not eliminate macrophage ROCK1 expression and increased ROCK1 activity. The RhoA deletion effect on macrophage phenotype, structure and polarity was different for each subtype. Moreover, our study indicates that the up-regulation of ROCK1 activity in RhoA-deleted macrophages and macrophage phenotype/polarity are dependent on non-apoptotic Caspase-3 and are sensitive to Caspase-3 inhibition. These novel findings will revise/complement our understanding of RhoA pathway regulation of cell structure and polarity. PMID- 26875771 TI - Comparing the effect of bleach and water baths on skin barrier function in atopic dermatitis: a split-body randomized controlled trial. PMID- 26875772 TI - Conserved stem fragment from H3 influenza hemagglutinin elicits cross-clade neutralizing antibodies through stalk-targeted blocking of conformational change during membrane fusion. AB - Currently available influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies due to the mutability of virus sequences and conformational changes during protective immunity, thereby limiting their efficacy. This problem needs to be addressed by further understanding the mechanisms of neutralization and finding the desired neutralizing site during membrane fusion. This study specifically focused on viruses of the H3N2 subtype, which have persisted as a principal source of influenza-related morbidity and mortality in humans since the 1968 influenza pandemic. Through sequence alignment and epitope prediction, a series of highly conserved stem fragments (spanning 47 years) were found and coupled to the Keyhole Limpet Hemocyanin (KLH) protein. By application of a combinatorial display library and crystal structure modeling, a stem fragment immunogen, located at the turning point of the HA neck undergoing conformational change during membrane fusion with both B- and T-cell epitopes, was identified. After synthesis of the optimal stem fragment using a multiple antigen peptide (MAP) system, strong humoral immune responses and cross-clade neutralizing activities against strains from the H3 subtype of group 2 influenza viruses after animal immunizations were observed. By detection of nuclear protein immunofluorescence with acid bypass treatment, antisera raised against MAP4 immunogens of the stem fragment showed the potential to inhibit the conformational change of HA in stem-targeted virus neutralization. The identification of this conserved stem fragment provides great potential for exploitation of this site of vulnerability in therapeutic and vaccine design. PMID- 26875773 TI - Good's syndrome and hypoparathyroidism combined with hypocalcaemia, hypokalemia, hypomagnesemia, and hypophosphatemia-Case report. PMID- 26875774 TI - Altered expression of miR-125a-5p in thymoma-associated myasthenia gravis and its down-regulation of foxp3 expression in Jurkat cells. AB - Myasthenia gravis is an autoantibody-mediated and T cell-dependent autoimmune disease of neuromuscular junctions. Thymomas may play a crucial role in the pathogenesis of thymoma-associated myasthenia gravis (TAMG), but the thymic pathogenesis of TAMG is unknown. MicroRNAs (miRNAs) are non-coding RNA molecules 21-24 nt in length that regulate the expression of their target genes in a post transcriptional manner. In this study, we used a miRNA microarray chip to identify, for the first time, 137 miRNAs in normal tissue adjacent to the thymoma from TAMG patients that were significantly dysregulated compared with normal thymus controls. We confirmed the differential expression of miR-125a-5p in larger samples using quantitative real-time polymerase chain reaction (qRT-PCR). Using bioinformatics analysis, we identified the foxp3 3' untranslated region (UTR) as a target of miR-125a-5p. Importantly, miR-125a-5p expression exhibited a negative correlation with foxp3 expression in normal tissue adjacent to the thymoma from TAMG patients. Furthermore, we demonstrated that the expression of the foxp3 gene was modulated by miR-125a-5p in Jurkat cells. Taken together, our results suggest that the abnormal expression of miR-125a-5p and its effect on foxp3 expression are likely involved in the pathogenesis of TAMG. PMID- 26875775 TI - Progesterone suppressed vasoconstriction in human umbilical vein via reducing calcium entry. AB - The aim of this study was to evaluate the actions of progesterone on human umbilical vein (HUV) from normal pregnancies and the possible underlying mechanisms involved. HUV rings were suspended in organ baths and exposed to progesterone followed by phenylephrine (PE) or serotonin (5-HT). Progesterone suppressed PE- or 5-HT-induced vasoconstriction in HUV rings. The inhibitory effect induced by progesterone was not influenced by nitric oxide syntheses inhibitor, prostaglandins syntheses blocker, the integrity of endothelium, selective progesterone receptor or potassium channel antagonists. Further testing showed that progesterone and nifedipine (a blocker for L-type calcium channels) produced similar inhibitory effects on PE-, 5-HT-, Bay-k8644-, KCl-induced vasoconstriction in Krebs solution as well as CaCl2-induced vasoconstriction in Ca(2+)-free Krebs solution. But the inhibitory effect of mibefradil (mibe, a blocker for L-type (CaV1.2) and T-type calcium channels (CaV3.2)) on PE-, 5-HT induced vasoconstriction was significantly greater than progesterone or nifedipine in Krebs solution. Furthermore, progesterone did not affect the vasoconstriction caused by PE, 5-HT, or caffeine in Ca(2+)-free Krebs solution. In addition, incubation HUV with progesterone did not change CaV1.2 and progesterone receptor (PR) expressions. The results gained demonstrated that progesterone could suppress multiple agonist-induced vasoconstrictions in HUV, mainly due to a reduction of calcium entry through L-type calcium channels, not endothelium-dependent vascular relaxation pathways, potassium channels, or Ca(2+) release from intracellular stores, providing new information important to further understanding the contribution of progesterone in the regulation of the placental fetal circulation. PMID- 26875776 TI - The case for plant-made veterinary immunotherapeutics. AB - The excessive use of antibiotics in food animal production has contributed to resistance in pathogenic bacteria, thereby triggering regulations and consumer demands to limit their use. Alternatives for disease control are therefore required that are cost-effective and compatible with intensive production. While vaccines are widely used and effective, they are available against a minority of animal diseases, and development of novel vaccines and other immunotherapeutics is therefore needed. Production of such proteins recombinantly in plants can provide products that are effective and safe, can be orally administered with minimal processing, and are easily scalable with a relatively low capital investment. The present report thus advocates the use of plants for producing vaccines and antibodies to protect farm animals from diseases that have thus far been managed with antibiotics; and highlights recent advances in product efficacy, competitiveness, and regulatory approval. PMID- 26875777 TI - Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip. AB - Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. PMID- 26875778 TI - Neural plasticity and behavior - sixty years of conceptual advances. AB - This brief review summarizes 60 years of conceptual advances that have demonstrated a role for active changes in neuronal connectivity as a controller of behavior and behavioral change. Seminal studies in the first phase of the six decade span of this review firmly established the cellular basis of behavior - a concept that we take for granted now, but which was an open question at the time. Hebbian plasticity, including long-term potentiation and long-term depression, was then discovered as being important for local circuit refinement in the context of memory formation and behavioral change and stabilization in the mammalian central nervous system. Direct demonstration of plasticity of neuronal circuit function in vivo, for example, hippocampal neurons forming place cell firing patterns, extended this concept. However, additional neurophysiologic and computational studies demonstrated that circuit development and stabilization additionally relies on non-Hebbian, homoeostatic, forms of plasticity, such as synaptic scaling and control of membrane intrinsic properties. Activity-dependent neurodevelopment was found to be associated with cell-wide adjustments in post synaptic receptor density, and found to occur in conjunction with synaptic pruning. Pioneering cellular neurophysiologic studies demonstrated the critical roles of transmembrane signal transduction, NMDA receptor regulation, regulation of neural membrane biophysical properties, and back-propagating action potential in critical time-dependent coincidence detection in behavior-modifying circuits. Concerning the molecular mechanisms underlying these processes, regulation of gene transcription was found to serve as a bridge between experience and behavioral change, closing the 'nature versus nurture' divide. Both active DNA (de)methylation and regulation of chromatin structure have been validated as crucial regulators of gene transcription during learning. The discovery of protein synthesis dependence on the acquisition of behavioral change was an influential discovery in the neurochemistry of behavioral modification. Higher order cognitive functions such as decision making and spatial and language learning were also discovered to hinge on neural plasticity mechanisms. The role of disruption of these processes in intellectual disabilities, memory disorders, and drug addiction has recently been clarified based on modern genetic techniques, including in the human. The area of neural plasticity and behavior has seen tremendous advances over the last six decades, with many of those advances being specifically in the neurochemistry domain. This review provides an overview of the progress in the area of neuroplasticity and behavior over the life-span of the Journal of Neurochemistry. To organize the broad literature base, the review collates progress into fifteen broad categories identified as 'conceptual advances', as viewed by the author. The fifteen areas are delineated in the figure above. This article is part of the 60th Anniversary special issue. PMID- 26875779 TI - Screening for abdominal aortic aneurysms. AB - Ultrasonography remains the screening modality of choice for abdominal aortic aneurysms despite many advances in imaging modalities. Several randomized trials were performed that demonstrated the effectiveness of ultrasound-based screening to reduce aneurysm-related mortality. Ultrasound is both cost effective and low risk. Controversies do persist in selecting the appropriate populations for screening, and several national societies have set recommendations. PMID- 26875780 TI - Maternal thyroid function in pregnant women with a breech presentation in late gestation. PMID- 26875781 TI - Primary hyperhidrosis: Implications on symptoms, daily life, health and alcohol consumption when treated with botulinum toxin. AB - Primary hyperhidrosis affects approximately 3% of the population and reduces quality of life in affected persons. Few studies have investigated the symptoms of anxiety, depression and hazardous alcohol consumption among those with hyperhidrosis and the effect of treatment with botulinum toxin. The first aim of this study was to investigate the effect of primary hyperhidrosis on mental and physical health, and alcohol consumption. Our second aim was to study whether and how treatment with botulinum toxin changed these effects. One hundred and fourteen patients answered questionnaires regarding hyperhidrosis and symptoms, including hyperhidrosis disease severity scale (HDSS), visual analog scale (VAS) 10-point scale for hyperhidrosis symptoms, hospital anxiety and depression scale (HADS), alcohol use disorder identification test (AUDIT) and short-form health survey (SF-36) before treatment with botulinum toxin and 2 weeks after. The age of onset of hyperhidrosis was on average 13.4 years and 48% described heredity for hyperhidrosis. Significant improvements were noted in patients with axillary and palmar hyperhidrosis regarding mean HDSS, VAS 10-point scale, HADS, SF-36 and sweat-related health problems 2 weeks after treatment with botulinum toxin. Changes in mean AUDIT for all participants were not significant. Primary hyperhidrosis mainly impairs mental rather than physical aspects of life and also interferes with specific daily activities of the affected individuals. Despite this, our patients did not show signs of anxiety, depression or hazardous alcohol consumption. Treatment with botulinum toxin reduced sweat-related problems and led to significant improvements in HDSS, VAS, HADS and SF-36 in our patients. PMID- 26875782 TI - Imaging viral RNA using multiply labeled tetravalent RNA imaging probes in live cells. AB - Viruses represent an important class of pathogens that have had an enormous impact on the health of the human race. They are extraordinarily diverse; viral particles can range in size from ~80nm to ~10MUm in length, and contain genomes with RNA or DNA strands. Regardless of their genome type, RNA species are frequently generated as a part of their replication process, and for viruses with RNA genomes, their loading into the virion represents a critical step in the creation of infectious particles. RNA imaging tools represent a powerful approach to gain insight into fundamental viral processes, including virus entry, replication, and virion assembly. Imaging viral processes in live cells is critical due to both the heterogeneity of these processes on a per cell basis, and the inherent dynamics of these processes. There are a number of methods for labeling RNA in live cells; we'll introduce the myriad of methods and then focus on one approach for labeling viral RNA, using multiply-labeled tetravalent RNA imaging probes (MTRIPs), which do not require engineering of the target RNAs. We feel this approach is advantageous given many viral genomes may not tolerate large nucleotide insertions into their sequences. PMID- 26875783 TI - Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles. AB - It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane's electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 MUg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy dispersive spectroscopy and immunohistochemistry. PMID- 26875785 TI - Chronic use of pravastatin reduces insulin exocytosis and increases beta-cell death in hypercholesterolemic mice. AB - We have previously demonstrated that hypercholesterolemic LDL receptor knockout (LDLr(-/-)) mice secrete less insulin than wild-type mice. Removing cholesterol from isolated islets using methyl-beta-cyclodextrin reversed this defect. In this study, we hypothesized that in vivo treatment of LDLr(-/-) mice with the HMGCoA reductase inhibitor pravastatin would improve glucose-stimulated insulin secretion. Female LDLr(-/-) mice were treated with pravastatin (400mg/L) for 1-3 months. Isolated pancreatic islets were assayed for insulin secretion rates, intracellular calcium oscillations, cholesterol levels, NAD(P)H and SNARE protein levels, apoptosis indicators and lipidomic profile. Two months pravastatin treatment reduced cholesterol levels in plasma, liver and islets by 35%, 25% and 50%, respectively. Contrary to our hypothesis, pravastatin treatment increased fasting and fed plasma levels of glucose and decreased markedly (40%) fed plasma levels of insulin. In addition, ex vivo glucose stimulated insulin secretion was significantly reduced after two and three months (36-48%, p<0.05) of pravastatin treatment. Although reducing insulin secretion and insulinemia, two months pravastatin treatment did not affect glucose tolerance because it improved global insulin sensitivity. Pravastatin induced islet dysfunction was associated with marked reductions of exocytosis-related SNARE proteins (SNAP25, Syntaxin 1A, VAMP2) and increased apoptosis markers (Bax/Bcl2 protein ratio, cleaved caspase-3 and lower NAD(P)H production rates) observed in pancreatic islets from treated mice. In addition, several oxidized phospholipids, tri- and diacylglycerols and the proapoptotic lipid molecule ceramide were identified as markers of pravastatin-treated islets. Cell death and oxidative stress (H2O2 production) were confirmed in insulin secreting INS-1E cells treated with pravastatin. These results indicate that chronic treatment with pravastatin impairs the insulin exocytosis machinery and increases beta-cell death. These findings suggest that prolonged use of statins may have a diabetogenic effect. PMID- 26875784 TI - Genome size and ploidy influence angiosperm species' biomass under nitrogen and phosphorus limitation. AB - Angiosperm genome sizes (GS) range c. 2400-fold, and as nucleic acids are amongst the most phosphorus- (P) and nitrogen (N)-demanding cellular biomolecules, we test the hypothesis that a key influence on plant biomass and species composition is the interaction between N and P availability and plant GS. We analysed the impact of different nutrient regimes on above-ground biomass of angiosperm species with different GS, ploidy level and Grime's C-S-R (competitive, stress tolerant, ruderal) plant strategies growing at the Park Grass Experiment (Rothamsted, UK), established in 1856. The biomass-weighted mean GS of species growing on plots with the addition of both N and P fertilizer were significantly higher than that of plants growing on control plots and plots with either N or P. The plants on these N + P plots are dominated by polyploids with large GS and a competitive plant strategy. The results are consistent with our hypothesis that large genomes are costly to build and maintain under N and P limitation. Hence GS and ploidy are significant traits affecting biomass growth under different nutrient regimes, influencing plant community composition and ecosystem dynamics. We propose that GS is a critical factor needed in models that bridge the knowledge gap between biodiversity and ecosystem functioning. PMID- 26875786 TI - Broadband coherent Raman spectroscopy running at 24,000 spectra per second. AB - We present a Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy technique that achieves broadband CARS measurements at an ultrahigh scan rate of more than 20,000 spectra/s - more than 20 times higher than that of previous broadband coherent Raman scattering spectroscopy techniques. This is made possible by an integration of a FT-CARS system and a rapid-scanning retro reflective optical path length scanner. To demonstrate the technique's strength, we use it to perform broadband CARS spectroscopy of the transient mixing dynamics of toluene and benzene in the fingerprint region (200-1500 cm(-1)) with spectral resolution of 10 cm(-1) at a record high scan rate of 24,000 spectra/s. Our rapid scanning FT-CARS technique holds great promise for studying chemical dynamics and wide-field label-free biomedical imaging. PMID- 26875787 TI - A nanoparticulate pre-chemosensitizer for efficacious chemotherapy of multidrug resistant breast cancer. AB - Small-molecule chemosensitizers can reverse cancer multidrug resistance (MDR), thus significantly improving the in vitro effect of chemotherapy drugs for MDR cancer cells, however, their in vivo effects are not always very good, because they are difficult to effectively accumulate in tumor and enter the same cancer with chemotherapy drugs after systemic administration due to individual biopharmaceutical properties. To overcome these limitations, here we study a novel nanoparticular pre-chemosensitizer which can be also used as nanocarrier of chemotherapy drugs. We take an 'all in one' approach to develop a self-assembled nanoparticle formula of amphiphilic poly(curcumin-dithiodipropionic acid)-b poly(ethylene glycol)-biotin. The nanoparticle is capable of tumor-targeted delivery, responsive degradation at the intracellular level of glutathione and subsequent intracellular co-release of the chemosensitizer curcumin and the encapsulated chemotherapeutic drug doxorubicin to maximize a synergistic effect of chemosensitization and chemotherapy. We demonstrate that the antitumor efficacy of nanoparticle is much superior to that of doxorubicin in the multidrug resistant MCF-7/ADR xenografted nude mice. PMID- 26875788 TI - Impact of a cytomegalovirus kinase inhibitor on infection and neuronal progenitor cell differentiation. AB - Human cytomegalovirus (HCMV) is the leading cause of congenital infections. Symptomatic newborns present with a range of sequelae including disorders of the CNS such as visual impairment, microcephaly, mental retardation and hearing loss. HCMV congenital infection causes gross changes in brain morphology and disturbances in glial and neuronal distribution, number and migration. In these studies, we have evaluated the effectiveness of the antiviral maribavir in inhibiting HCMV infections of ES cell-derived neuronal progenitor cells (NPC). We used EZ-spheres generated from H9 ES cells which are pre-rosette NPCs that retain long-term potential to differentiate into diverse central and peripheral neural lineages following directed differentiation. Our results demonstrate that the maribavir disrupts HCMV replication and viral yield in undifferentiated EZ-sphere derived NPCs. In addition, we observed that maribavir limits HCMV replication and reduces the percentage of infected cells during differentiation of NPCs. Finally, early steps in differentiation are maintained during infection by treating with maribavir, likely an indirect effect resulting from decreased viral spread. Future studies of NPC proliferation and differentiation during infection treated with maribavir could provide the impetus for studying maribavir as an antiviral agent for congenital HCMV disease. PMID- 26875789 TI - Insights from Analysis of Binding Sites of Human Meprins: Screening of Inhibitors by Molecular Dynamics Simulation Study. AB - Human meprin-alpha and-beta are important regulators of angiogenesis, cancer, inflammation, fibrosis, and neurodegenerative diseases and hence important therapeutic targets. Meprins are the only astacin proteases that are expressed in membrane-bound and secreted form. The cleavage specificity of human meprins is similar in certain cases but differs markedly in others. The inhibitor selectivity of human meprins is controlled by the specific residues involved in binding at the active-site cleft of the proteases. Meprins are inhibited by various small molecular inhibitors as well as macromolecular endogenous inhibitors, making them good drug targets. In the current study, molecular dynamics simulation was performed for 10 ns on ten systems consisting of two apoenzymes of meprin -alpha/beta and eight complexes of human meprin-alpha and beta complexed to four inhibitors with different metal binding moieties and comparable Ki values. These simulation studies helped to elucidate the molecular details of how several parameters influence protein-inhibitor binding affinity. Analysis of the interaction energies of the protein-inhibitor complexes revealed the diverse binding nature of this series of inhibitors. Several structural segments of human meprins exhibited certain conformational changes during the simulation time course. Among the inhibitors studied captopril had a different disposition in the meprin-bound complexes compared to the other three inhibitors, namely Pro- Leu-Gly-hydroxamate, galardin and EDTA. Comparison of the interaction energies for each system helped us to conclude that the hydroxamic acid-based inhibitors are the most potent inhibitors of meprins. PMID- 26875790 TI - Maintenance of aversive memories shown by fear extinction-impaired phenotypes is associated with increased activity in the amygdaloid-prefrontal circuit. AB - Although aversive memory has been mainly addressed by analysing the changes occurring in average populations, the study of neuronal mechanisms of outliers allows understanding the involvement of individual differences in fear conditioning and extinction. We recently developed an innovative experimental model of individual differences in approach and avoidance behaviors, classifying the mice as Approaching, Balancing or Avoiding animals according to their responses to conflicting stimuli. The approach and avoidance behaviors appear to be the primary reactions to rewarding and threatening stimuli and may represent predictors of vulnerability (or resilience) to fear. We submitted the three mice phenotypes to Contextual Fear Conditioning. In comparison to Balancing animals, Approaching and Avoiding mice exhibited no middle- or long-term fear extinction. The two non-extinguishing phenotypes exhibited potentiated glutamatergic neurotransmission (spontaneous excitatory postsynaptic currents/spinogenesis) of pyramidal neurons of medial prefrontal cortex and basolateral amygdala. Basing on the a priori individuation of outliers, we demonstrated that the maintenance of aversive memories is linked to increased spinogenesis and excitatory signaling in the amygdala-prefrontal cortex fear matrix. PMID- 26875791 TI - Bednar Tumor Mimicking Congenital Melanocytic Nevus. PMID- 26875792 TI - Lentigo Maligna: Keys to Dermoscopic Diagnosis. AB - Dermoscopy is a noninvasive technique that improves accuracy in the diagnosis of cutaneous lesions. The recognition and differential diagnosis of lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging, especially in the early stages when there are no distinctive clinical features. Early diagnosis and appropriate treatment can improve prognosis. Several dermoscopic features have been described for LM and LMM. The following 4 criteria in combination have achieved a diagnostic sensitivity of 89% and a specificity of 96%: asymmetric pigmented follicular openings, dark rhomboidal structures, slate gray dots, and slate gray globules. A biopsy is warranted when dermoscopic examination reveals a grayish coloring. For a flat pigmented lesion acquired in adulthood, a histopathological diagnosis of "atypical junctional nevus" is not to be accepted uncritically. LM and LMM can also appear in sites other than the face, and dermoscopy can facilitate their recognition. Dermoscopy is an essential tool for physical examination. PMID- 26875793 TI - Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction. AB - Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-beta) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid beta-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. PMID- 26875794 TI - CAV1 Prevents Gallbladder Cholesterol Crystallization by Regulating Biosynthesis and Transport of Bile Salts. AB - Cholesterol gallstone disease (CGD) is a hepatobiliary disorder which results from a biochemical imbalance in the gallbladder bile. Here we show that loss of CAV1 sensitized mice to lithogenic diet-induced gallbladder cholesterol crystallization, which was associated with dysregulation of several hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The combined effect of increased biliary cholesterol concentration and decreased biliary bile salt secretion in CAV1(-/-) mice led to an increased cholesterol saturation index and the formation of cholesterol crystals. At the signaling level, the ERK/AP-1 pathway seems to mediate the effects of CAV1 on biliary BA homeostasis and might be developed as a therapeutic target for CGD. We propose that CAV1 is an anti lithogenic factor and that the CAV1(-/-) mice may offer a convenient CGD model to develop therapeutic interventions for this disease. J. Cell. Biochem. 117: 2118 2127, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26875795 TI - Systematic investigations on the biodegradation and viscosity reduction of long chain hydrocarbons using Pseudomonas aeruginosa and Pseudomonas fluorescens. AB - The use of microorganisms has been researched extensively for possible applications related to hydrocarbon degradation in the petroleum industry. However, attempts to improve the effect of microorganisms on the viscosity of hydrocarbons, which find potential use in the development of robust models for biodegradation, have been rarely documented. This study investigates the degradation of long chain hydrocarbons, such as hexadecane and eicosane using Pseudomonas fluorescens PMMD3 (P. fluorescens) and Pseudomonas aeruginosa CPCL (P. aeruginosa). P. aeruginosa used here is isolated from petroleum contaminated sediments and the P. fluorescens is from the coastal area, and both have hydrocarbon degrading genes. The degradation of hydrocarbons is studied using carbon profiling and reduction in viscosity pre- and post-degradation of hydrocarbons. The carbon profiling has been obtained using gas chromatography mass spectroscopy (GC-MS), and Fourier transform infrared spectrometer (FTIR) results. GC-MS results have indicated an improved biodegradation of hydrocarbons by 77-93% in one day. The yield coefficients of biomass (YX/S) for P. aeruginosa and P. fluorescens using hexadecane as a carbon source are 1.35 and 0.81 g g(-1), and the corresponding values with eicosane are 0.84 and 0.88 g g(-1). The viscosity of hexadecane is reduced by the order of 53 and 47%, while that of eicosane was reduced by 53 and 65%, using P. aeruginosa and P. fluorescens, respectively. This study also presents information on the activity of enzymes responsible for the hydrocarbon degradation. Pseudomonas species have shown their use in potential applications for bioremediation, oil-spill treatment, and flow assurance. We believe that this study will also provide stringent tests for possible model development for the bioremediation of long chain paraffins suitable for oilfield applications. PMID- 26875796 TI - The risk of surgical never events. PMID- 26875797 TI - Working in paediatric emergency medicine. PMID- 26875799 TI - Blunt chest trauma: bony injury in the thorax. AB - The management of blunt chest trauma is an evolving concept with no clear current guidelines. This article explores the bony injuries associated with this, focusing on rib fractures and flail segments and the themes around investigation and best management. PMID- 26875800 TI - Blunt chest trauma: soft tissue injury in the thorax. AB - The management of blunt chest trauma is evolving. This article discusses the soft tissue injuries associated with blunt chest trauma. PMID- 26875801 TI - Shoulder replacements: a review. AB - Shoulder replacement surgery is a common elective surgical procedure for those with progressive osteoarthritis and rheumatoid arthritis. This review explores the history of shoulder replacements, the different types of replacements and their advantages or disadvantages. PMID- 26875802 TI - Liver biopsy: past, present and future. AB - Liver biopsy is an integral part of evaluation of liver disease. Indications and techniques have developed to allow functional and prognostic liver assessment, along with biochemistry and dynamic imaging, in both diffuse and focal liver disease. However, non-invasive techniques are changing the way clinicians use liver biopsy. PMID- 26875803 TI - Tracheostomies for the non-expert 2: routine and emergency care. AB - Recent reports have emphasized shortcomings in routine and emergency care leading to adverse outcomes in patients with tracheostomies. This two-part article provides a guide to the principles of care for staff looking after adult patients with tracheostomies in the hospital. The second part looks at routine and emergency care. PMID- 26875804 TI - Frailty and surgery. AB - Surgery in people aged over 65 years has led to many postoperative gains, although mortality and morbidity is higher than in younger counterparts. The problem is the vulnerability that comes with age, so these patients with complex needs require multidisciplinary care for the best outcomes. PMID- 26875805 TI - Demystifying professional support for trainees: what does it mean? AB - 'Professional support' is a commonly used term in medical training but it is not always clear what is meant by it and what the implications are for an individual trainee and his/her trainer. This article explores the concept of professional support in medical training. PMID- 26875806 TI - Sir Arthur Keith: distinguished conservator of the Hunterian Museum, London. PMID- 26875807 TI - Recurrent coronary spasm necessitating primary percutaneous coronary intervention. PMID- 26875808 TI - Survival of ingestion of a potentially lethal dose of caffeine. PMID- 26875809 TI - Accidental ingestion of two magnets: should we intervene? PMID- 26875810 TI - Cognitive dysfunction in patients with fibromyalgia. PMID- 26875812 TI - Should anaesthetic technique be modified for cancer surgery? PMID- 26875813 TI - Age-related macular degeneration. PMID- 26875814 TI - Diagnosing dementia. PMID- 26875815 TI - Urinary incontinence in older people. PMID- 26875816 TI - The antineoplastic drug flavopiridol reverses memory impairment induced by Amyloid-beta1-42 oligomers in mice. AB - The ectopic re-activation of cell cycle in neurons is an early event in the pathogenesis of Alzheimer's disease (AD), which could lead to synaptic failure and ensuing cognitive deficits before frank neuronal death. Cytostatic drugs that act as cyclin-dependent kinase (CDK) inhibitors have been poorly investigated in animal models of AD. In the present study, we examined the effects of flavopiridol, an inhibitor of CDKs currently used as antineoplastic drug, against cell cycle reactivation and memory loss induced by intracerebroventricular injection of Abeta1-42 oligomers in CD1 mice. Cycling neurons, scored as NeuN positive cells expressing cyclin A, were found both in the frontal cortex and in the hippocampus of Abeta-injected mice, paralleling memory deficits. Starting from three days after Abeta injection, flavopiridol (0.5, 1 and 3mg/kg) was intraperitoneally injected daily, for eleven days. Here we show that a treatment with flavopiridol (0.5 and 1mg/kg) was able to rescue the loss of memory induced by Abeta1-42, and to prevent the occurrence of ectopic cell-cycle events in the mouse frontal cortex and hippocampus. This is the first evidence that a cytostatic drug can prevent cognitive deficits in a non-transgenic animal model of AD. PMID- 26875817 TI - Optimization of a nanotechnology based antimicrobial platform for food safety applications using Engineered Water Nanostructures (EWNS). AB - A chemical free, nanotechnology-based, antimicrobial platform using Engineered Water Nanostructures (EWNS) was recently developed. EWNS have high surface charge, are loaded with reactive oxygen species (ROS), and can interact-with, and inactivate an array of microorganisms, including foodborne pathogens. Here, it was demonstrated that their properties during synthesis can be fine tuned and optimized to further enhance their antimicrobial potential. A lab based EWNS platform was developed to enable fine-tuning of EWNS properties by modifying synthesis parameters. Characterization of EWNS properties (charge, size and ROS content) was performed using state-of-the art analytical methods. Further their microbial inactivation potential was evaluated with food related microorganisms such as Escherichia coli, Salmonella enterica, Listeria innocua, Mycobacterium parafortuitum, and Saccharomyces cerevisiae inoculated onto the surface of organic grape tomatoes. The results presented here indicate that EWNS properties can be fine-tuned during synthesis resulting in a multifold increase of the inactivation efficacy. More specifically, the surface charge quadrupled and the ROS content increased. Microbial removal rates were microorganism dependent and ranged between 1.0 to 3.8 logs after 45 mins of exposure to an EWNS aerosol dose of 40,000 #/cm(3). PMID- 26875818 TI - Simvastatin and atorvastatin facilitates amyloid beta-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways. AB - One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid beta-protein (Abeta) in the brain. Abeta accumulation seems to arise from an imbalance between Abeta production and clearance. Neprilysin (NEP) and insulin-degrading enzyme (IDE) are the important Abeta-degrading enzymes in the brain, and deficits in their expression may promote Abeta deposition in patients with sporadic late-onset AD. Statins, which are used clinically for reducing cholesterol levels, can exert beneficial effects on AD. Therefore, we examined whether various statins are associated with Abeta degradation by inducing NEP and IDE expression, and then evaluating the relation between activation of intracellular signaling transduction, inhibition of cholesterol production, and morphological changes to astrocytes. Treating cultured rat astrocytes with simvastatin and atorvastatin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner. The decrease in NEP expression was a result of activation of extracellular signal regulated kinase (ERK) but not the reduction of cholesterol synthesis pathway. This NEP reduction was achieved by the release to the extracellular space of cultured astrocytes. Furthermore, the cultured medium prepared from simvastatin- and atorvastatin-treated astrocytes significantly induced the degradation of exogenous Abeta. These results suggest that simvastatin and atorvastatin induce the increase of Abeta degradation of NEP on the extracellular of astrocytes by inducing ERK-mediated pathway activity and that these reagents regulate the differential mechanisms between the secretion of NEP, the induction of cholesterol reduction, and the morphological changes in the cultured astrocytes. PMID- 26875819 TI - Prediction of an arc-tunable Weyl Fermion metallic state in Mo(x)W(1-x)Te2. AB - A Weyl semimetal is a new state of matter that hosts Weyl fermions as emergent quasiparticles. The Weyl fermions correspond to isolated points of bulk band degeneracy, Weyl nodes, which are connected only through the crystal's boundary by exotic Fermi arcs. The length of the Fermi arc gives a measure of the topological strength, because the only way to destroy the Weyl nodes is to annihilate them in pairs in the reciprocal space. To date, Weyl semimetals are only realized in the TaAs class. Here, we propose a tunable Weyl state in Mo(x)W(1-x)Te2 where Weyl nodes are formed by touching points between metallic pockets. We show that the Fermi arc length can be changed as a function of Mo concentration, thus tuning the topological strength. Our results provide an experimentally feasible route to realizing Weyl physics in the layered compound Mo(x)W(1-x)Te2, where non-saturating magneto-resistance and pressure-driven superconductivity have been observed. PMID- 26875820 TI - Cadmium accumulation and tolerance of Macleaya cordata: a newly potential plant for sustainable phytoremediation in Cd-contaminated soil. AB - Heavy metal pollution is a major concern of the public due to their threats to the safety of food chains. A 60-day pot experiment was conducted using Macleaya cordata as plant material to investigate the phytoremediation potential and anti oxidative responses of M. cordata under different Cd stress. Significant growth inhibition phenomenon and toxic symptoms were not detected in the experiment. The high biomass of the plant provided high accumulation capacity for Cd with an average dry weight of 3.6 g. The maximum extraction amount of Cd was 393 MUg.plant(-1), suggesting that this species had potential for phytoremediation of Cd-contaminated soil. A slight increase of chlorophyll (CHL) content was observed in Cd10 treatment. The plant was confirmed to have relatively high tolerance to the Cd stress on the basis of tolerance indexes (TI), relative water content, and CHLa/CHLb ratio. M. cordata could maintain high level of superoxide dismutase (SOD) activity under Cd stress, indicating strong tolerance capacity for reactive oxygen species (ROS) in plant cells. Catalase (CAT) activity show a certain range of decline in the experiment compare to the control. And peroxidase (POD) activity in leaves changed irregularly when compared to the control. The malondialdehyde (MDA) content increased as Cd concentration elevated compared to the control. In addition, as an inedible crop with relatively high economic value, M. cordata have shown the advantage of high biomass and high tolerance under Cd stress, which can provide a new plant resource for sustainable phytoremediation. PMID- 26875821 TI - Magnetic properties and element concentrations in lichens exposed to airborne pollutants released during cement production. AB - The content of selected elements (Al, As, Ca, Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, S, Ti, V and Zn) was measured in samples of the lichen Evernia prunastri exposed for 30, 90 and 180 days around a cement mill, limestone and basalt quarries and urban and agricultural areas in SW Slovakia. Lichens transplanted around the investigated quarries and the cement mill rapidly (30 days) reflected the deposition of dust-associated elements, namely Ca (at the cement mill and the limestone quarry) and Fe, Ti and V (around the cement mill and the basalt quarry), and their content remained significantly higher throughout the whole period (30-180 days) with respect to the surrounding environment. Airborne pollutants (such as S) progressively increased in the study area from 30 to 180 days. The magnetic properties of lichen transplants exposed for 180 days have been characterized and compared with those of native lichens (Xanthoria parietina) and neighbouring bark, soil and rock samples, in order to test the suitability of native and transplanted samples as air pollution magnetic biomonitors. The magnetic mineralogy was homogeneous in all samples, with the exception of the samples from the basalt quarry. The transplants showed excellent correlations between the saturation remanent magnetization (Mrs) and the content of Fe. Native samples had a similar magnetic signature, but the values of the concentration-dependent magnetic parameters were up to two orders of magnitude higher, reflecting higher concentrations of magnetic particles. The concentrations of As, Ca and Cr in lichens correlated with Mrs values after neglecting the samples from the basalt quarry, which showed distinct magnetic properties, suggesting the cement mill as a likely source. Conversely, Ti and Mn were mostly (but not exclusively) associated with dust from the basalt quarry. It is suggested that the natural geological characteristics of the substrate may strongly affect the magnetic properties of lichen thalli. Taking this into account, the results of this study point out the suitability of lichens as air pollution magnetic biomonitors. PMID- 26875822 TI - Culturable endophytic bacteria from the salt marsh plant Halimione portulacoides: phylogenetic diversity, functional characterization, and influence of metal(loid) contamination. AB - Halimione portulacoides is abundant in salt marshes, accumulates mercury (Hg), and was proposed as useful for phytoremediation and pollution biomonitoring. Endophytic bacteria promote plant growth and provide compounds with industrial applications. Nevertheless, information about endophytic bacteria from H. portulacoides is scarce. Endophytic isolates (n = 665) were obtained from aboveground and belowground plant tissues, from two Hg-contaminated sites (sites E and B) and a noncontaminated site (site C), in the estuary Ria de Aveiro. Representative isolates (n = 467) were identified by 16S rRNA gene sequencing and subjected to functional assays. Isolates affiliated with Proteobacteria (64 %), Actinobacteria (23 %), Firmicutes (10 %), and Bacteroidetes (3 %). Altererythrobacter (7.4 %), Marinilactibacillus (6.4 %), Microbacterium (10.2 %), Salinicola (8.8 %), and Vibrio (7.8 %) were the most abundant genera. Notably, Salinicola (n = 58) were only isolated from site C; Hoeflea (17), Labrenzia (22), and Microbacterium (67) only from belowground tissues. This is the first report of Marinilactibacillus in the endosphere. Principal coordinate analysis showed that community composition changes with the contamination gradient and tissue. Our results suggest that the endosphere of H. portulacoides represents a diverse bacterial hotspot including putative novel species. Many isolates, particularly those affiliated to Altererythrobacter, Marinilactibacillus, Microbacterium, and Vibrio, tested positive for enzymatic activities and plant growth promoters, exposing H. portulacoides as a source of bacteria and compounds with biotechnological applications. PMID- 26875823 TI - Combination of sunlight, oxidants, and Ce-doped TiO2 for phenol degradation. AB - The degradation of phenol was used as a model reaction to investigate the photocatalytic properties of cerium-doped (0.1 nominal atomic percent) TiO2 catalysts in the presence and in the absence of oxidants: persulfate (PS) or hydrogen peroxide (HP). Experiments were performed in batch reactors using either artificial light (ultraviolet or visible) or solar exposure during spring-summer seasons in La Plata City (34.90 degrees S, 57.92 degrees W, 15 MASL). The formation of hydroquinone, catechol, and p-benzoquinone was observed in all the experiments. Additionally, for the experiments with PS (with or without catalyst), evidence of the formation of dimers and trimers was found. Total degradation of phenol (250 MUM) was achieved with doped material and 7 mM of PS (two doses) after 3 h of solar exposure (H SUV, T = 2.9 +/- 0.6 105 J m-2). PMID- 26875825 TI - Printable photonic crystals with high refractive index for applications in visible light. AB - Nanoimprint lithography (NIL) of functional high-refractive index materials has proved to be a powerful candidate for the inexpensive manufacturing of high resolution photonic devices. In this paper, we demonstrate the fabrication of printable photonic crystals (PhCs) with high refractive index working in the visible wavelengths. The PhCs are replicated on a titanium dioxide-based high refractive index hybrid material by reverse NIL with almost zero shrinkage and high-fidelity reproducibility between mold and printed devices. The optical responses of the imprinted PhCs compare very well with those fabricated by conventional nanofabrication methods. This study opens the road for a low-cost manufacturing of PhCs and other nanophotonic devices for applications in visible light. PMID- 26875824 TI - Differences in Quality of Life Between Bendamustine-Rituximab and R-CHOP/R-CVP in Patients With Previously Untreated Advanced Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma. AB - BACKGROUND: We previously reported results of the phase III, randomized, noninferiority trial comparing bendamustine-rituximab (BR) with standard R-CHOP (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone)/R-CVP (rituximab/cyclophosphamide/vincristine/prednisone) in previously untreated advanced indolent non-Hodgkin and mantle cell lymphomas. Here we report health related quality of life (HRQOL) results from the trial. METHODS: HRQOL, as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), was a secondary end point. Differences between group means in global health status (GHS), 5-item functioning, and 9 symptoms/single-item measures at week 1 of cycle 1 and end-of- cycles 3 and 6 were examined using the screening (baseline) score as a covariate in analysis of covariance. RESULTS: Overall EORTC QLQ-C30 compliance was 75.2%, 89.5%, and 89.9% at week 1 of cycle 1 and end-of-cycles 3 and 6, respectively. Patients treated with BR reported improvements in Cognitive Functioning, Physical Functioning, Social Functioning, Emotional Functioning, and GHS as well as reduction in dyspnea, constipation, and fatigue at some, but not all, time points. Patients treated with standard therapy reported less nausea/vomiting at one time point. CONCLUSION: Compared with patients treated with standard therapy, patients treated with BR reported better quality of life in several areas. PMID- 26875826 TI - 3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction. AB - Desktop three-dimensional (3D) printers (D3DPs) have become a popular tool for fabricating personalized consumer products, favored for low cost, easy operation, and other advantageous qualities. This study focused on the potential for using D3DPs to successfully, rapidly, and economically print customized implants at medical clinics. An experiment was conducted on a D3DP-printed anterior cruciate ligament surgical implant using a rabbit model. A well-defined, orthogonal, porous PLA screw-like scaffold was printed, then coated with hydroxyapatite (HA) to improve its osteoconductivity. As an internal fixation as well as an ideal cell delivery system, the osteogenic scaffold loaded with mesenchymal stem cells (MSCs) were evaluated through both in vitro and in vivo tests to observe bone ligament healing via cell therapy. The MSCs suspended in Pluronic F-127 hydrogel on PLA/HA screw-like scaffold showed the highest cell proliferation and osteogenesis in vitro. In vivo assessment of rabbit anterior cruciate ligament models for 4 and 12 weeks showed that the PLA/HA screw-like scaffold loaded with MSCs suspended in Pluronic F-127 hydrogel exhibited significant bone ingrowth and bone-graft interface formation within the bone tunnel. Overall, the results of this study demonstrate that fabricating surgical implants at the clinic (fab@clinic) with D3DPs can be feasible, effective, and economical. PMID- 26875828 TI - Tumour immunology: Microbiota predicts side-effects of immunotherapy. PMID- 26875827 TI - Characterization of DWARF14 Genes in Populus. AB - Strigolactones are a new class of plant hormones regulating shoot branching and symbiotic interactions with arbuscular mycorrhizal fungi. Studies of branching mutants in herbaceous plants have identified several key genes involved in strigolactone biosynthesis or signaling. The strigolactone signal is perceived by a member of the alpha/beta-fold hydrolase superfamily, known as DWARF14 (D14). However, little is known about D14 genes in the woody perennial plants. Here we report the identification of D14 homologs in the model woody plant Populus trichocarpa. We showed that there are two D14 homologs in P. trichocarpa, designated as PtD14a and PtD14b that are over 95% similar at the amino acid level. Expression analysis indicated that the transcript level of PtD14a is generally more abundant than that of PtD14b. However, only PtD14a was able to complement Arabidopsis d14 mutants, suggesting that PtD14a is the functional D14 ortholog. Amino acid alignment and structural modeling revealed substitutions of several highly conserved amino acids in the PtD14b protein including a phenylalanine near the catalytic triad of D14 proteins. This study lays a foundation for further characterization of strigolactone pathway and its functions in the woody perennial plants. PMID- 26875829 TI - Tumour immunology: Innate surveillance. PMID- 26875831 TI - Macrophages: Embracing those nerves. PMID- 26875832 TI - A green synthesis route for the phase and size tunability of copper antimony sulfide nanocrystals with high yield. AB - Until now, it is a great challenge for the controllable synthesis of copper antimony sulfide (CAS) nanocrystals (NCs), as the reactivity of precursors is quite difficult to be controlled during the synthesis process. In the present work, a novel solution-based method is proposed to synthesize CAS NCs by choosing N,N'-diphenylthiourea as the sulfide precursor, which is favorable for balancing the relative reactivity of Cu and Sb ions. It is found that three phases (CuSbS2, Cu12Sb4S13 and Cu3SbS4) of CAS NCs with size tunability were successfully synthesized for the first time. To the best of our knowledge, the lowest reaction temperature of 110 degrees C and the highest yield over 90% for CAS NCs were also achieved for the first time, which may be considered to be a green synthesis route compared with other conventional methods. Optical properties indicate that the as-prepared CAS NCs have strong optical absorption in the visible light region of the solar spectrum, and we also observed the band gap tunability of CuSbS2 and Cu3SbS4 materials for the first time. PMID- 26875830 TI - Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease. AB - CD4(+) T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4(+) T cell plasticity by examining the molecular mechanisms that regulate it - from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells. PMID- 26875833 TI - Rapid Hydrogen Peroxide release from the coral Stylophora pistillata during feeding and in response to chemical and physical stimuli. AB - Corals make use of different chemical compounds during interactions with prey, predators and aggressors. Hydrogen Peroxide (H2O2) is produced and released by a wide range of organisms as part of their defense against grazers or pathogens. In coral reefs, the large fluxes and relatively long half-life of H2O2, make it a potentially important info-chemical or defense molecule. Here we describe a previously unstudied phenomenon of rapid H2O2 release from the reef-building coral Stylophora pistillata during feeding on zooplankton and in response to chemical and physical stimuli. Following stimuli, both symbiotic and bleached corals were found to rapidly release H2O2 to the surrounding water for a short period of time (few minutes). The H2O2 release was restricted to the site of stimulus, and an increase in physical stress and chemical stimuli concentration resulted in elevated H2O2 release. Omission of calcium (a key regulator of exocytotic processes) from the experimental medium inhibited H2O2 release. Hence we suggest that H2O2 is actively released in response to stimuli, rather than leaking passively from the coral tissue. We estimate that at the site of stimulus H2O2 can reach concentrations potentially high enough to deter predators or motile, potentially pathogenic, bacteria. PMID- 26875834 TI - La-Activated Bicyclo-oligomerization of Acetylene to Naphthalene. AB - We report the first example of metal-mediated acetylene bicyclopentamerization to form naphthalene in the gas phase. The bicyclic aromatic compound was observed in a complex with La. The La(naphthalene) complex was formed by the reaction of laser-ablated La atoms with acetylene molecules in a molecular beam source and was characterized by mass-analyzed threshold ionization spectroscopy. The bicyclo oligomerization reaction occurs through sequential acetylene additions coupled with dehydrogenation. Three intermediates in the reaction have been identified: lanthanacyclopropene [La(C2H2)], La(cyclobut-1-en-3-yne) [La(C4H2)], and La(benzyne) [(La(C6H4)]. The metal-ligand bonding in the three intermediates is considerably different from that in the La(naphthalene) complex, as suggested by accurately measured adiabatic ionization energies. PMID- 26875835 TI - The pharmacological effects of intramuscular administration of alfaxalone combined with medetomidine and butorphanol in dogs. AB - The pharmacological effects of intramuscular (IM) administration of alfaxalone combined with medetomidine and butorphanol were evaluated in 6 healthy beagle dogs. Each dog received three treatments with a minimum 10-day interval between treatments. The dogs received an IM injection of alfaxalone 2.5 mg/kg (ALFX), medetomidine 2.5 ug/kg and butorphanol 0.25 mg/kg (MB), or their combination (MBA) 1 hr after the recovery from their instrumentation. Endotracheal intubation was attempted, and dogs were allowed to breath room air. Neuro-depressive effects (behavior changes and subjective scores) and cardiorespiratory parameters (rectal temperature, heart rate, respiratory rate, direct blood pressure, central venous pressure and blood gases) were evaluated before and at 2 to 120 min after IM treatment. Each dog became lateral recumbency, except for two dogs administered the MB treatment. The duration was longer in the MBA treatment compared with the ALFX treatment (100 +/- 48 min vs 46 +/- 13 min). Maintenance of the endotracheal tube lasted for 60 +/- 24 min in five dogs administered the MBA treatment and for 20 min in one dog administered the ALFX treatment. Cardiorespiratory variables were maintained within clinically acceptable ranges, although decreases in heart and respiratory rates, and increases in central venous pressure occurred after the MBA and MB treatments. The MBA treatment provided an anesthetic effect that permitted endotracheal intubation without severe cardiorespiratory depression in healthy dogs. PMID- 26875836 TI - Predictors of fatal outcomes resulting from acute Escherichia coli mastitis in dairy cows. AB - To evaluate the prognostic criteria for identifying cows at an increased risk of a fatal outcome from acute Escherichia coli mastitis, the potential cut-off values for five diagnostic parameters associated with a high mortality were determined by receiver operator characteristic curve analysis. These criteria were hematocrit value >32%, blood non-esterified fatty acid concentration >0.4 mEq/l, antithrombin activity <120%, platelet count <15 * 10(4)/ml and presence of dysstasia. Exceeding the cut-off values for at least three parameters on day 2 after onset predicted fatality (predictive value 87.5). When these prognostic criteria were applied to 34 clinical cases, cows that met three criteria were seven times more likely to die than cows that met fewer than three criteria. PMID- 26875837 TI - Comparison of pharmacokinetics of tramadol between young and middle-aged dogs. AB - This study aimed to compare the pharmacokinetics of tramadol between young and middle-aged dogs. Tramadol (4 mg/kg) was administered intravenously (IV) to young and middle-aged dogs (2 and 8-10 years, respectively). Plasma concentrations of tramadol were measured using high-performance liquid chromatography (HPLC), and its pharmacokinetics best fit a two-compartment model. The volume of distribution (Vd), elimination half-life (t1/2,beta) and total body clearance (CLtot) of the young group were 4.77 +/- 1.07 l/kg, 1.91 +/- 0.26 hr and 29.9 +/- 7.3 ml/min/kg, respectively, while those of the middle-aged group were 4.73 +/- 1.43 l/kg, 2.39 +/- 0.97 hr and 23.7 +/- 5.4 ml/min/kg, respectively. Intergroup differences in the t1/2,beta and CLtot were significant (P<0.05). In conclusion, tramadol excretion was significantly prolonged in middle-aged dogs. PMID- 26875838 TI - Maternal betaine supplementation during gestation modifies hippocampal expression of GR and its regulatory miRNAs in neonatal piglets. AB - Methyl donor nutrients are critical for embryonic development of brain. Hippocampus is the most susceptible brain region to various factors including prenatal supply of methyl donors. Glucocorticoid receptor (GR) expressed in hippocampus is involved in the regulation of energy homeostasis and stress sensitivity. Hippocampal GR expression is highly susceptible to epigenetic regulation, yet the effect of maternal methyl donor supplementation on epigenetic regulation of GR transcription in offspring hippocampus remains unclear. In this study, we fed sows with betaine (3 g/kg) throughout the gestation and analyzed the hippocampal expression of GR mRNA and its variants, as well as the CpG methylation status of the promoter and the microRNAs predicted to target 3' UTR of porcine GR gene in neonatal piglets. Total GR mRNA (P<0.01) and its variants GR 1-4 (P<0.05) and 1-9,10 (P<0.01), were significantly higher in the hippocampus of betaine-treated piglets, while the content of GR protein was not significantly changed. The CpGs located in the -1650 ~ -1515 segment of GR gene were hypermethylated (P<0.05). The hippocampal expression of miR-130b (P<0.05), miR 181a (P<0.05) and miR-181d (P<0.01) was significantly up-regulated. The targeting efficacy of miR-130b and miR-181d was validated in vitro using dual-luciferase reporter assay system. Our results demonstrate that maternal betaine supplementation during gestation enhances GR mRNA expression in offspring hippocampus, which involves alterations in miRNAs expression. PMID- 26875839 TI - Regulation of cell migration and inflammation by ceramide 1-phosphate. AB - Ceramide 1-phosphate (C1P) is a bioactive sphingolipid metabolite first shown to regulate cell growth and death. Subsequent studies revealed that C1P was a potent stimulator of cytosolic phospholipase A2 (cPLA2) with ensuing release of arachidonic acid and prostaglandin biosynthesis. The latter findings placed C1P on the list of pro-inflammatory metabolites. More recently, C1P was found to potently stimulate cell migration, an action that is associated to diverse physiological effects, as well as to inflammatory responses and tumor dissemination. The implication of C1P in inflammation has gained further interest in the last few years due to the discovery that it can exert anti-inflammatory actions in some cell types and tissues. In particular, C1P has been demonstrated to inhibit pro-inflammatory cytokine release and blockade of the pro-inflammatory transcription factor NF-kappaB in some cell types, as well as to reduce airway inflammation and lung emphysema. The present review is focused on novel aspects of C1P regulation of cell migration and the impact of C1P as novel anti inflammatory agent. GLOSS: Ceramide 1-phosphate (C1P) is a phosphosphingolipid with potent biological activities. It promotes cell growth and survival, and is a key regulator of cell migration. Both C1P and the enzyme that catalyzes its biosynthesis, ceramide kinase, are implicated in inflammatory responses. Although C1P has pro-inflammatory properties, it reduces pulmonary emphysema and exerts anti-inflammatory actions in the lung. Synthetic C1P analogs may be promising tools to treat lung inflammation. PMID- 26875840 TI - Nursing home nurses' experiences of resident transfers to the emergency department: no empathy for our work environment difficulties. AB - AIMS AND OBJECTIVES: To explore the experiences of nursing home nurses when they transfer residents from nursing homes to the emergency department in Taiwan. BACKGROUND: The transfer of residents between nursing homes and emergency departments challenges continuity of care. Understanding nursing home nurses' experiences during these transfers may help to improve residents' continuity of care. However, few empirical data are available on these nurses' transfer experiences worldwide, and none could be found in Asian countries. DESIGN: Qualitative descriptive study. METHODS: Data were collected from August 2012-June 2013 in audiotaped, individual, in-depth interviews with 25 nurses at five nursing homes in Taiwan. Interview transcripts were analysed by constant comparative analysis. RESULTS: Analysis of interview transcripts revealed that the core theme of nursing home nurses' transfer experience was discontinuity in nursing home to emergency department transitions. This core theme comprised three themes: discontinuity in family involvement, discontinuity in medical resources and expectations, and discontinuity in nurses' professional role. CONCLUSIONS: Nursing home nurses need a working environment that is better connected to residents' family members and more immediate and/or easier access to acute care for residents. Communication between nurses and residents' family could be improved by using text messages or social media by mobile phones, which are widely used in Taiwan and worldwide. To improve access to acute care, we suggest developing a real-time telehealth transfer system tailored to the medical culture and policies of each country. This system should facilitate communication among nursing home staff, family members and hospital staff. RELEVANCE TO CLINICAL PRACTICE: Our findings on nurses' experiences during transfer of nursing home residents to the emergency department can be used to design more effective transfer policies such as telemedicine systems in Taiwan and other Asian countries or in those with large populations of Chinese immigrants. PMID- 26875841 TI - Processes in healthcare teams that include nurse practitioners: what do patients and families perceive to be effective? AB - AIMS AND OBJECTIVES: To explore patient and family perceptions of team effectiveness of teams those include nurse practitioners in acute and primary care. BACKGROUND: Nurse practitioners provide safe and effective care. Patients are satisfied with the care provided by nurse practitioners. Research examining patient and family perceptions of team effectiveness following the implementation of nurse practitioners in teams is lacking. DESIGN: A descriptive qualitative design was used. METHODS: We used purposeful sampling to identify participants in four clinical specialties. We collected data from March 2014-January 2015 using semi-structured interviews and demographic questionnaires. Content analysis was used. Descriptive statistics were generated. RESULTS: Participants (n = 49) believed that the teams were more effective after the implementation of a nurse practitioner and this was important to them. They described processes that teams with nurse practitioners used to effectively provide care. These processes included improved communication, involvement in decision-making, cohesion, care coordination, problem-solving, and a focus on the needs of patients and families. Participants highlighted the importance of interpersonal team dynamics. A human approach, trust, being open to discussion, listening to patient and family concerns and respect were particularly valued by participants. Different processes emerged as priorities when data were examined by speciality. However, communication, trust and taking the time to provide care were the most important processes. CONCLUSION: The study provides new insights into the views of patients and families and micro-level processes in teams with nurse practitioners. The relative importance of each process varied according to the patient's health condition. Patients and providers identified similar team processes. Future research is needed to identify how team processes influence care outcomes. RELEVANCE TO CLINICAL PRACTICE: The findings can support patients, clinicians and decision-makers to determine the processes to focus on to promote effective team functioning, and involve patients and families as team members. PMID- 26875842 TI - Nutritional screening of patients at a memory clinic--association between patients' and their relatives' self-reports. AB - AIMS AND OBJECTIVES: To compare individual reports by patients and relatives (proxy) of the Nutritional Form For the Elderly and relate the Nutritional Form For the Elderly scores to Mini Mental Status Examination scores, weight loss, Body Mass Index, five-point Clock Drawing Test and background variables. BACKGROUND: Undernutrition or risk of undernutrition is a significant problem among people with dementia. A poor nutritional state increases the risk of infections, delayed convalescence after acute illness and reduced quality of life. DESIGN: A cross-sectional study. METHOD: Application of the Nutritional Form For the Elderly in addition to clinical nutrition parameters and cognitive tests in a memory clinic among 213 persons referred for assessment due to possible cognitive impairment or dementia. RESULTS: Patients' and proxy Nutritional Form For the Elderly scores yielded comparative results. Nutritional Form For the Elderly scores >=6 (medium to high risk of undernutrition) were found in 32% of the patients vs. 43% of proxy. Mean Mini Mental Status Examination score was 23.2 (SD 4.5) and 50% failed the Clock Drawing Test. Involuntary weight loss was reported by 42% of the patients, and in 26% of the patients, Body Mass Index values were below 22 kg/m(2) , indicating undernutrition. By regression analysis, Clock Drawing Test (p = 0.019) and Mini Mental Status Examination (p = 0.04) might predict the risk of reduced nutritional status. CONCLUSION: The study demonstrates that a significant proportion of patients at our memory clinic were at nutritional risk. Corresponding results exist between patients' and proxy Nutritional Form For the Elderly scores; however, the patients assessed themselves more well-nourished as compared to proxy assessment. The discrepancies seem to increase with more severe cognitive impairment. Females and single-dwelling individuals were at higher risk of undernutrition compared to males and cohabitants. RELEVANCE TO CLINICAL PRACTICE: Self-reporting and proxy-rating seem both applicable for nutritional screening among moderate cognitive impaired. Cognitive decline seems to affect the accuracy when patients rate themselves. A reduced Mini Mental Status Examination and/or failed Clock Drawing Test might predict the risk of undernutrition. PMID- 26875844 TI - Corrigendum. PMID- 26875843 TI - Changes in decision-making among Italian nurses and nursing students over the last 15 years. AB - AIMS AND OBJECTIVES: The study aimed at identifying the cognitive strategies used by nurses and nursing students in using information for clinical decision-making and comparing such abilities retrospectively, over the past 15 years. BACKGROUND: Within the context of Italian healthcare professions, a process of cultural role development has been ongoing for several years, in the wake of normative and institutional changes. However, the ability to use information for clinical nursing decision-making has been little studied. DESIGN: Three independent observational studies, with convenience samples of Italian clinical nurses and nursing students recruited at three time-points (1997, 2007, 2012). METHODS: The total sample consisted of 2855 subjects (1406 Nurses and 1449 Nursing Students). Nurses from various clinical realities were subdivided into two classes (less or more than 10 years of experience). Data were collected according to Jenkins' 'Clinical Decision Making in Nursing Scale'. RESULTS: A trend of decreasing skills in information strategies emerged in both nurses and nursing students from 1997-2012. All subjects totalled values in the lowest class (0-130) of the Clinical Decision Making in Nursing Scale of final scoring. Particularly evident were the decreased scores for nursing students from 1997 to 2007-2012. Comparing nurses with nursing students, the former had significantly higher scores. Comparing experienced nurses with novices, the former again had significantly higher scores. Interestingly, in 1997, nursing students had higher scores than nurses, although this result was not confirmed for the other 2 years. CONCLUSIONS: Results showed consistently decreased competence in the use of information skills, particularly among nursing students. RELEVANCE TO CLINICAL PRACTICE: All transformations in training in university-level teaching of nursing show that decision-making skills are continually and significantly worsening. These results are of special interest in view of changes in professional and educational systems. PMID- 26875845 TI - Superoxide Ion: Generation and Chemical Implications. AB - Superoxide ion (O2(*-)) is of great significance as a radical species implicated in diverse chemical and biological systems. However, the chemistry knowledge of O2(*-) is rather scarce. In addition, numerous studies on O2(*-) were conducted within the latter half of the 20th century. Therefore, the current advancement in technology and instrumentation will certainly provide better insights into mechanisms and products of O2(*-) reactions and thus will result in new findings. This review emphasizes the state-of-the-art research on O2(*-) so as to enable researchers to venture into future research. It comprises the main characteristics of O2(*-) followed by generation methods. The reaction types of O2(*-) are reviewed, and its potential applications including the destruction of hazardous chemicals, synthesis of organic compounds, and many other applications are highlighted. The O2(*-) environmental chemistry is also discussed. The detection methods of O2(*-) are categorized and elaborated. Special attention is given to the feasibility of using ionic liquids as media for O2(*-), addressing the latest progress of generation and applications. The effect of electrodes on the O2(*-) electrochemical generation is reviewed. Finally, some remarks and future perspectives are concluded. PMID- 26875846 TI - Functional Effectiveness of Inpatient Rehabilitation After Heart Transplantation. AB - BACKGROUND: Heart transplantation (HT) is the treatment of choice for many patients with end-stage heart failure who remain symptomatic despite optimal medical therapy, but no study has looked directly into functional improvement of HT patients after an inpatient rehabilitation program. OBJECTIVE: To determine functional improvement in HT patients who completed an inpatient rehabilitation program. DESIGN: Retrospective study. SETTING: An inpatient rehabilitation facility (IRF) associated with a tertiary care hospital. PATIENTS: Seventeen patients admitted between March 2011 and September 2014 after HT. METHODS: Demographic, clinical, and functional data (admission and discharge Functional Independence Measure [FIM] scores) were recorded. Change in FIM scores and FIM efficiency (change in FIM score/length of stay) were analyzed. FIM outcomes for HT patients were compared with regional and national averages for patients undergoing an inpatient rehabilitation program for cardiac debility. As a secondary outcome, we evaluated whether body mass index of HT patients had an impact on FIM gains in an IRF. Individual FIM items were analyzed for trends. Results are reported as mean +/- SD. RESULTS: Twelve male and 5 female patients with mean age of 61.2 +/- 4.5 years were identified. Three patients were readmitted to acute hospital because of complications. For those 14 patients who completed the IRF stay, the mean admission and discharge motor FIM were 51.5 (+/ 14.6) and 74.7 (+/-12.0), respectively. The mean admission and discharge cognition FIM were 30.9 (+/-3.2) and 32.9 (+/-1.7), respectively. The mean total FIM gain was 26.9 +/- 13.3 (P < .05). The mean FIM efficiency was 3.2 (+/-2.0). After admission to an IRF, 82% were discharged home with statistically significant improvement in their functional ability. In addition, all individual FIM items improved from admission to discharge. There was positive relationship between body mass index and FIM gain but this was not statistically significant. CONCLUSIONS: An inpatient rehabilitation program appears to positively impact optimal outcomes (functional recovery and discharge to home) for selected patients with HT and is comparable with regional and national FIM gain and efficiency for patients admitted to IRFs with other cardiac conditions. PMID- 26875847 TI - Methyl jasmonate induction of tanshinone biosynthesis in Salvia miltiorrhiza hairy roots is mediated by JASMONATE ZIM-DOMAIN repressor proteins. AB - Jasmonic acid (JA) is an important plant hormone involved in regulation of many aspects of plant growth and development including secondary metabolism and JASMONATE ZIM-DOMAIN (JAZ) proteins are key components in JA signal processes. In this study, two new JAZ genes named SmJAZ3 and SmJAZ9 were cloned from S. miltiorrhiza hairy roots and characterized. Expression profiles under methyl jasmonate (MJ) treatment revealed that SmJAZ3 and SmJAZ9 were both MJ-responsive. Subcellular localization assay showed that SmJAZ3 was located in nucleus while SmJAZ9 was preferentially in nucleus. Expression of SmJAZ3 and SmJAZ9 in S. miltiorrhiza hairy roots differently affected the production of tanshinone. Over expression of SmJAZ3 or SmJAZ9 in hairy roots produced lower level of tanshinone compared with the control, tanshinone production was as low as 0.077 mg/g DW in line SmJAZ3-3 and 0.266 mg/g DW in line SmJAZ9-22. Whereas, down-regulation of SmJAZs enhanced tanshione production, the content of tanshinone increased to 2.48 fold in anti-SmJAZ3-3 line, and 1.35-fold in anti-SmJAZ9-23 line. Our work indicated that SmJAZ3 and SmJAZ9 are involved in regulation of tanshinone biosynthesis and act as repressive transcriptional regulators in the JA signaling pathway, which paves the way to further dissect molecular mechanism in details in the future. PMID- 26875848 TI - Optometry's role in managing patients with glaucoma. PMID- 26875849 TI - Sports eyewear protective standards. AB - Eye injuries sustained during sport comprise up to 20 per cent of all injuries to the eye serious enough for medical attention to be sought. The prevalence of eye injuries in sport is not easily assessed due to lack of authoritative participation rates, so most studies report total numbers in a time period. The evidence on the proportion of all ocular injuries that are from sport is reviewed. The relative frequencies in different sports are compared in a qualitative manner and the sports with greater numbers of ocular injuries are detailed. In common with occupational injuries to the eye, most sports eye injuries are considered preventable. The hierarchy of action for occupational risk is detailed and adapted to use in a sports scenario. All the available international, regional and national standards on sports eye protection are detailed and their provisions compared. The major function of the standards is to provide adequate protection against the hazard of the sport concerned. These are detailed and compared as a function of energy transfer. Eye protection must not introduce additional or secondary hazards (for instance, fracturing into sharp fragments on impact) and not introduce features that would deter the wearing of eye protection (for instance, restricting field of view to impede playing the sport). The provisions of the standards intended to limit secondary hazards are detailed and compared. The need for future work in standards writing and the activities of the International Standardization Organization in sports eye protection are detailed. PMID- 26875850 TI - A review of proximal inputs to the near response. AB - Maddox proposed that the perceived nearness of a target could influence the ocular vergence response. Proximal inputs have been used to refer to all static and dynamic cues to depth other than disparity and blur. In this paper, we review a number of studies in which proximal influences have been assessed. While general agreement exists that proximal contributions are significant when blur and disparity cues are absent (open-loop conditions), there are conflicting reports on the role of proximal vergence and accommodation under closed-loop conditions. PMID- 26875851 TI - Optical quality comparison among different Boston contact lens materials. AB - BACKGROUND: The aim was to assess the optical quality of four Boston contact lens materials with an optical device based on Schlieren interferometry. METHODS: The NIMO TR1504 (Lambda-X, Nivelles, Belgium) was used to measure higher-order aberrations and their corresponding root mean square values of four different rigid gas permeable contact lenses made from four different Boston materials: EO, ES, XO and XO2 . For each lens, 30 measurements were performed with two optical apertures: 3.0 mm and 6.0 mm. The modulation transfer function, point spread function, Strehl ratio and a simulation of the image provided by the lens were computed from the Zernike coefficients measured up to the fourth order. RESULTS: The root mean square error of higher-order aberrations varied significantly with material type for both optical apertures (p < 0.01). The largest difference was obtained between the Boston EO and the Boston ES materials (for a 6.0 mm aperture), the mean difference being (8.3 +/- 0.2) * 10(-2) um. The modulation transfer functions, point spread functions and Strehl ratio values were similar among all Boston materials at the smaller optical aperture; however, differences between each material were more apparent for the 6.0 mm aperture, with the Boston ES material exhibiting the best optical quality. CONCLUSIONS: In terms of all metrics analysed, all Boston materials examined showed comparable optical quality for a 3.0 mm aperture but the Boston ES material displayed the best optical quality for a 6.0 mm optical aperture. PMID- 26875852 TI - The effect of viewing distance on responses to the pattern glare test. AB - BACKGROUND: We investigated whether symptoms of pattern glare were affected by viewing distance, as distinct from spatial frequency, because of an association between symptoms and anomalies of accommodation and vergence. METHODS: One hundred young adults viewed gratings with spatial frequencies of 0.3, 2.3 and 9.4 cycles per degree (cpd) at four test distances (0.4, 0.8, 1.6 and 3.2 metres). Participants were asked to grade the presence of 15 symptoms of visual perceptual distortions and discomfort, on a scale from zero (no symptoms) to 10 (maximum perceptual and somatic symptoms). RESULTS: The viewing distance did not affect the nature and strength of symptoms, when viewing gratings with similar spatial frequencies. The symptoms increased with spatial frequency (p < 0.008 for all comparisons). CONCLUSIONS: The symptoms from the Pattern Glare Test do not appear to be modulated by the changes in accommodation and vergence associated with viewing distance, at least in an unselected sample of students. The highest spatial frequency of the current Pattern Glare Test was 9.4 cpd at 0.4 metre and this is insufficiently high to measure the reduction in symptoms at high spatial frequencies. If assessing relative aversion to gratings of different spatial frequencies, it may be useful to increase the testing distance to 0.6 metre so as to increase the spatial frequency of the third grating to 14.2 cpd. PMID- 26875853 TI - Optical densitometric measurements of the cornea and lens in children with allergic rhinoconjunctivitis. AB - BACKGROUND: Our aim was to investigate the impact of allergic rhinoconjunctivitis on corneal and lenticular optical densitometry, pachymetry and anterior chamber depth in children. METHODS: Fifty-four patients who had allergic rhinoconjunctivitis (study group) and 54 age-matched healthy children (control group) were recruited in this cross-sectional and comparative study. Corneal and lenticular optical densitometry, pachymetry, corneal volume and anterior chamber depth measurements were taken with the Scheimpflug imaging system. RESULTS: The lens density and anterior chamber depth were similar between the groups (p > 0.05), while corneal density and thickness were significantly higher in the study group (p < 0.05). Although the corneal volume was higher in children with allergic rhinoconjunctivitis, the difference was not statistically significant (p = 0.07). CONCLUSIONS: The cornea is affected in allergic rhinoconjunctivitis in respect to optical density and thickness, while the anterior chamber and lens are not influenced. PMID- 26875854 TI - Self-recognition of recurrences among patients with exudative age-related macular degeneration. AB - PURPOSE: The aim was to investigate factors influencing a patient's self recognition of the recurrence of exudative changes secondary to age-related macular degeneration (AMD). METHODS: In this retrospective study, we reviewed medical records for patients with exudative AMD who were diagnosed with a recurrence of exudation. Various parameters were compared, including age, sex, diagnosis, spectacle use, visual acuity before and after the recurrence and the extent of the decrease in visual acuity. In addition, visual acuity and unaided vision before the recurrence were compared in patients who did not use eyeglasses. RESULTS: Forty-eight eyes from 48 patients were included in the analysis. Twenty-seven patients (56.3 per cent) identified a decrease in visual acuity. These patients had better visual acuity before the recurrence (p = 0.023) and reported a greater decrease in visual acuity (p = 0.005) than patients who did not identify a visual change. Patients who wore spectacles were also more likely to notice the change in their visual acuity (p = 0.027). Visual acuity was significantly better than uncorrected vision (p < 0.001). CONCLUSIONS: Patients who do not use eyeglasses or who have relatively poor vision tend not to promptly recognise visual deterioration caused by the recurrence of exudation. Prescribing eyeglasses may facilitate accurate self-recognition of the recurrence of exudation in cases where vision can be improved with correction. PMID- 26875855 TI - Profile of paediatric low vision population: a retrospective study from Nepal. AB - BACKGROUND: Childhood blindness and low vision have become major public health problems in developing countries. The purpose of this study was to categorise the causes of visual impairment according to aetiology and provide detailed local information on visually impaired children seeking low-vision services in a tertiary eye centre in Nepal. METHODS: A retrospective study was conducted of all visually impaired children (visual acuity of less than 6/18 in the better eye), aged less than 17 years seen in the low-vision clinic at the Sagarmatha Chaudhary Eye Hospital in Lahan between January 1, 2012 and December 31, 2013. RESULTS: Of the 558 visually impaired children, the majority were males, 356 (63.7 per cent). More than half (56.5 per cent) of the children were in the 11 to 16 years age group. Many of the low-vision children (52.9 per cent) were identified as having moderate visual impairment (visual acuity less than 6/18 to 6/60). Most children were diagnosed with childhood (36.2 per cent) or genetic (35.5 per cent) aetiology, followed by prenatal (22.2 per cent) and perinatal (6.1 per cent) aetiologies. Refractive error and amblyopia (20.1 per cent), retinitis pigmentosa (14.9 per cent) and macular dystrophy (13.4 per cent) were the most common causes of paediatric visual impairment. Nystagmus (50.0 per cent) was the most common cause of low vision in the one to five years age group, whereas refractive error and amblyopia were the major causes in the six to 10 and 11 to 16 years age group (17.6 and 22.9 per cent, respectively). Many of the children (86.0 per cent) were prescribed low-vision aids and 72.0 per cent of the low-vision aid users showed an improvement in visual acuity either at distance or near. CONCLUSION: Paediatric low vision has a negative impact on the quality of life in children. Data from this study indicate that knowledge about the local characteristics and aetiological categorisation of the causes of low vision are essential in tackling paediatric visual impairment. The findings also signify the importance of early intervention to ensure a better quality of life. PMID- 26875856 TI - Retinal tissue thickness in type 1 and type 2 diabetes. AB - BACKGROUND: The objective was to investigate full retinal and inner retinal thickness in individuals with type 1 and type 2 diabetes. METHODS: Eighty-four individuals with type 1 diabetes (T1DM), 67 individuals with type 2 diabetes (T2DM) and 42 non-diabetic individuals (control group) were enrolled. Participants underwent full retinal thickness evaluation in the central retinal, parafoveal and perifoveal zones and in the retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC), using spectral domain optical coherence tomography. As a preliminary step, the key variables of interest - age, sex, diabetic retinopathy (DR), duration of diabetes and HbA1c levels - were analysed and compared between the three groups. Full retinal thickness, RNFL and GCC thicknesses were also compared between the groups. The relationship between the type of diabetes and retinal tissue thickness was explored, adjusting for the five potential confounders. RESULTS: Compared to individuals with T1DM, individuals with T2DM had significantly reduced full retinal thickness in the parafovea and perifovea and reduced RNFL and GCC thickness. The mean differences were six (p = 0.020), seven (p = 0.008), six (p = 0.021) and four micrometres (p = 0.013) for the parafovea, perifovea, RNFL and GCC thicknesses, respectively. Thicknesses within the central zone (p = 0.018) and at the parafovea (p = 0.007) were significantly reduced in T2DM when compared to the control group. After adjusting for age, sex, diabetic retinopathy, duration of diabetes and HbA1c levels, the relationship between type of diabetes and retinal tissue thickness was not statistically significant (p > 0.056). CONCLUSION: Retinal tissue thickness is not significantly different between type 1 and type 2 diabetes, when adjusted for age, sex, diabetic retinopathy, duration of diabetes and HbA1c levels. PMID- 26875857 TI - Minor trauma resulting in subretinal haemorrhage with choroidal rupture: a case of subtle pseudoxanthoma elasticum in a child. PMID- 26875858 TI - Retinal vasculitis associated with autoantibodies of primary Sjogren's syndrome after cataract surgery. PMID- 26875859 TI - A case of pigmented, free-floating vitreous cyst treated with micropulse diode laser. PMID- 26875860 TI - Re: Contact lens management of keratoconus. PMID- 26875861 TI - Utility of folate receptor alpha immunohistochemistry in cytology specimens of metastatic breast carcinoma, metastatic serous carcinoma of Mullerian origin, and primary lung adenocarcinoma. AB - BACKGROUND: Folate receptor alpha (FRA) overexpression by immunohistochemistry (IHC) has been shown to various degrees in histologic specimens from breast ductal carcinoma (DC), serous carcinoma of Mullerian origin (SCM), and primary lung adenocarcinoma (ADC) among others. Antifolate therapies have recently shown usefulness in FRA overexpressing malignancies. We assessed the feasibility for detecting FRA overexpression by IHC in cytologic cell blocks (CB) from the aforementioned carcinomas. METHOD: Cases of breast DC, SCM and lung ADC were included. The CB were immunostained with FRA employing mAb 26B.3.F2 (Biocare Medical, Concord, CA). FRA staining was scored qualitatively, by intensity, and staining area. RESULTS: 4/20 (20%) triple negative breast cancer (TNBC), 27/29 (93%) SCM, and 20/22 (91%) lung ADC showed positive FRA immunoreactivity. All ER/PR positive (n = 5) and Her2-neu positive (n = 5) DC were negative with FRA IHC. CONCLUSIONS: FRA expression can be detected with a higher degree of confidence in SCM (93%) and lung ADC (91%) in CB, and to a lesser degree in TNBC. Our data also shows that FRA expression by IHC was more frequently associated with TNBC (20%) when compared with ER/PR positive or Her2neu positive breast cancers. FRA overexpression detected by IHC in CB is highly concordant with the published results of surgical specimens from SCM and lung ADC and less so from TNBC. Hence, IHC FRA analysis can be performed in the CB preparation with a high degree of confidence in SCM and lung ADC. PMID- 26875862 TI - Fluorinated triazapentadienyl ligand supported ethyl zinc(ii) complexes: reaction with dioxygen and catalytic applications in the Tishchenko reaction. AB - Ethyl zinc complexes [N{(C3F7)C(Dipp)N}2]ZnEt, [N{(C3F7)C(Cy)N}2]ZnEt, [N{(CF3)C(2,4,6-Br3C6H2)N}2]ZnEt and [N{(C3F7)C(2,6-Cl2C6H3)N}2]ZnEt have been synthesized from the corresponding 1,3,5-triazapentadiene and diethyl zinc. X-ray data show that [N{(C3F7)C(Dipp)N}2]ZnEt has a distorted trigonal planar geometry at the zinc center. The triazapentadienyl ligand binds to zinc in a kappa(2) mode. The zinc-ethyl bonds of [N{(C3F7)C(Dipp)N}2]ZnEt, [N{(C3F7)C(Cy)N}2]ZnEt, [N{(CF3)C(2,4,6-Br3C6H2)N}2]ZnEt and [N{(C3F7)C(2,6-Cl2C6H3)N}2]ZnEt readily undergo oxygen insertion upon exposure to dry air to produce the corresponding zinc-ethoxy or zinc-ethylperoxy compounds. The ethoxy zinc adducts {[N{(CF3)C(2,4,6-Br3C6H2)N}2]ZnOEt}2 and {[N{(C3F7)C(2,6-Cl2C6H3)N}2]ZnOEt}2 as well as the ethylperoxy zinc adduct {[N{(C3F7)C(Cy)N}2]ZnOOEt}2 have been isolated and fully characterized by several methods including X-ray crystallography. They feature dinuclear structures with four-coordinate zinc sites and bridging-ethoxy or -ethylperoxy groups. The ethyl zinc complexes catalyze the Tishchenko reaction of benzaldehyde under solventless conditions affording benzyl benzoate. The reaction of ethyl zinc complexes with dioxygen and their catalytic behaviour in the Tishchenko reaction are affected by the electronic and steric factors of the triazapentadienyl ligand. {[N{(C3F7)C(Cy)N}2]ZnOOEt}2 is an excellent reagent for the epoxidation of trans chalcone. PMID- 26875863 TI - Development of a light-regulated cell-recovery system for non-photosynthetic bacteria. AB - BACKGROUND: Recent advances in the understanding of photosensing in biological systems have enabled the use of photoreceptors as novel genetic tools. Exploiting various photoreceptors that cyanobacteria possess, a green light-inducible gene expression system was previously developed for the regulation of gene expression in cyanobacteria. However, the applications of cyanobacterial photoreceptors are not limited to these bacteria but are also available for non-photosynthetic microorganisms by the coexpression of a cyanobacterial chromophore with a cyanobacteria-derived photosensing system. An Escherichia coli-derived self aggregation system based on Antigen 43 (Ag43) has been shown to induce cell self aggregation of various bacteria by exogenous introduction of the Ag43 gene. RESULTS: An E. coli transformant harboring a plasmid encoding the Ag43 structural gene under a green light-regulated gene expression system derived from the cyanobacterium Synechocystis sp. PCC6803 was constructed. Ag43 was inserted downstream of the cpcG 2 promoter P cpcG2 , and its expression was regulated by green light induction, which was achieved by the functional expression of cyanobacterial CcaS/CcaR by coexpressing its chromophore synthesis gene cassette in E. coli. E. coli transformants harboring this designed system self-aggregated under green light exposure and precipitated, whereas transformants lacking the green light induction system did not. The green light induction system effectively functioned before the cell culture entered the stationary growth phase, and approximately 80 % of the cell culture was recovered by simple decantation. CONCLUSION: This study demonstrated the construction of a cell recovery system for non-photosynthetic microorganisms induced by exposure of cells to green light. The system was regulated by a two-component regulatory system from cyanobacteria, and cell precipitation was mediated by an autotransporter protein, Ag43. Although further strict control and an increase of cell recovery efficiency are necessary, the system represents a novel tool for future bioprocessing with reduced energy and labor required for cell recovery. PMID- 26875864 TI - Intussusception as clinical presentation of primary non-Hodgkin lymphoma of the colon in a HIV-patient. AB - Intestinal intussusception rarely occurs in the adult population and accounts only for 1% to 5% of all the causes of intestinal obstruction. This complication is more frequent in the small bowel and can be due to different aetiologies, including inflammatory, infectious or neoplastic diseases. Malignancies account for 50% to 60% of all cases of colon invagination. The gastrointestinal (GI) tract is the most common site for extra-nodal non-Hodgkin lymphomas (NHL), representing 5% to 20% of all the cases. However, primary NHL of the GI tract is a very infrequent clinic-pathological entity and accounts only for 1% to 4% of all the neoplasms of the GI tract. Primary NHL of the colon is a rare disease and it comprises only 0.2% to 1.2% of all colonic malignancies. Here we describe a case of an AIDS adult patient who developed an intussusception secondary to a primary large B cell lymphoma of the transverse colon. English and Spanish literature was reviewed. PMID- 26875865 TI - Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis. AB - Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. PMID- 26875866 TI - Graded Control of Microtubule Severing by Tubulin Glutamylation. AB - Microtubule-severing enzymes are critical for the biogenesis and maintenance of complex microtubule arrays in axons, spindles, and cilia where tubulin detyrosination, acetylation, and glutamylation are abundant. These modifications exhibit stereotyped patterns suggesting spatial and temporal control of microtubule functions. Using human-engineered and differentially modified microtubules we find that glutamylation is the main regulator of the hereditary spastic paraplegia microtubule severing enzyme spastin. Glutamylation acts as a rheostat and tunes microtubule severing as a function of glutamate number added per tubulin. Unexpectedly, glutamylation is a non-linear biphasic tuner and becomes inhibitory beyond a threshold. Furthermore, the inhibitory effect of localized glutamylation propagates across neighboring microtubules, modulating severing in trans. Our work provides the first quantitative evidence for a graded response to a tubulin posttranslational modification and a biochemical link between tubulin glutamylation and complex architectures of microtubule arrays such as those in neurons where spastin deficiency causes disease. PMID- 26875868 TI - Oxygen vacancies as active sites for H2S dissociation on the rutile TiO2(110) surface: a first-principles study. AB - Spin-polarized DFT+U computations have been performed to investigate the role of oxygen vacancies in dissociating H2S on the rutile TiO2(110) surface. A bridged O2c atom is demonstrated to be the most energetically favorable oxygen vacancy site, which makes V(O2c) an electron donator center and induces an isolated defect level with narrowed band gaps. A H2S molecule is adsorbed dissociatively over V(O2c), but molecularly on the perfect surface. For H2S dissociation, the HS/H intermediate state reveals the best thermal stability on both defected and perfect surfaces. Moreover, potential energy surface analysis shows that V(O2c) reduces markedly the energy barriers for the paths along H2S dissociation. This indicates oxygen vacancies to be efficient trap centers for H2S dissociation, as evidenced by a significant interfacial charge transfer promoted by vacancies. This work could provide insights into the role of oxygen vacancies in facilitating the decomposition of H2S on rutile TiO2(110) surface. PMID- 26875867 TI - Structure and Engineering of Francisella novicida Cas9. AB - The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 A resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5'-NGG-3' PAM, and used the structural information to create a variant that can recognize the more relaxed 5'-YG-3' PAM. Furthermore, we demonstrated that the FnCas9-ribonucleoprotein complex can be microinjected into mouse zygotes to edit endogenous sites with the 5'-YG-3' PAM, thus expanding the target space of the CRISPR-Cas9 toolbox. PMID- 26875869 TI - [Theoretical reflection on the place of memory and temporal cognitive mechanisms in addictive disorders]. AB - INTRODUCTION: Addictions can be regarded as cognitive disorders related to neurobiological impairments. On the one hand, some cognitive impairments occur as a result of substance intake and withdrawal upon stopping intake, while, on the other hand, cognitive mechanisms are responsible for initiating and maintaining addiction. In this review, we detail the memory and temporal mechanisms involved in this pathology. METHODOLOGY: We reviewed the literature dedicated to the mechanisms of conditioning association between a substance and a context, and the memory and temporal mechanisms involved in the maintenance of addiction. Cognitive impairments in this context are accompanied by both short-term and long term neurobiological disorders. RESULTS: Drug-context conditioning is dependent on learning abilities in rats and humans, and it is the first step towards the development of an addiction. In fact, with the beginning of an addiction, it is the context associated with the substance intake, which determines the reinforcing factors (such as pleasure in the case of drug consumption) for the development of an addiction. Maintenance of addiction is related to the persistence of this association between context and substance. Furthermore, the impulsiveness of patients renders them unable to delay their gratification. Consequently, even if delayed gratifications are more valuable, patients prefer immediate gratification such as substance use. DISCUSSION: The memory and temporal mechanisms of addiction are central to the initiation and maintenance of drug addiction. They also affect patients' ability to develop projects for the future. The salience of the memory association between drug and context is accompanied by a decline in autobiographical memories, which become poor and lacking in detail. It is probably these impairments which are responsible for the difficulty that the patients have while investigating their story during psychotherapy. On the other hand, given that even though delayed gratification is greater patients prefer immediate gratification, they have difficulty making plans for the future and constructing their own personality. These cognitive impairments are sustained by neurobiological correlates such as dopamine dysregulation in the short-term and changes in neural plasticity in the cortico meso-limbic system in the long term. CONCLUSION: We reviewed full arguments which highlight that addiction is mediated by cognitive mechanisms which are related on the one hand to clinical symptoms and, on the other hand, to neurobiological alterations. According to the literature, memory and time mechanisms seem to be central to the initiation and maintenance of addictive behaviours. More research is needed to improve our knowledge of the cognitive mechanisms of addiction and to develop new tools for treating patients. PMID- 26875870 TI - From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis. AB - Metastasis is a multistep process that involves the dissemination of cells from the primary tumor and colonization of distant secondary organs. Epithelial cells at the invasive front of a carcinoma acquire an enhanced migratory phenotype in a process called epithelial-to-mesenchymal transition (EMT). This cellular plasticity seems to drive the initiation of metastasis. Identifying important molecules and understanding their molecular mechanisms is a key to cancer prognosis and the development of therapeutics for late stage malignancies. Recent advances in sequencing technology uncovered that the mammalian genome is pervasively transcribed into many nonprotein-coding RNAs including the class of long noncoding RNA, a.k.a. lncRNA. Several lncRNAs are differentially expressed in carcinomas and they are emerging as potent regulators of tumor progression and metastasis. Here, we review the diverse molecular mechanisms, cellular roles and regulatory patterns that are becoming apparent for the noncoding transcriptome. Chromatin modification, epigenetic regulation, alternative splicing and translational control by MALAT1, HOTAIR and TRE lncRNAs represent important examples of lncRNA-mediated control of cell migration and invasion, EMT and metastasis. Beyond these better characterized examples, numerous additional transcripts have been associated with cancer metastasis, but their functional roles await their discovery. PMID- 26875871 TI - Can a simple question predict prolonged uroflow lag times in children? AB - OBJECTIVE: It is our experience that some children with bowel and bladder dysfunction (BBD) who have bladder neck dysfunction had a tendency to complain of dizziness when we subjected the patients with dizziness to tilt-table testing to confirm the diagnosis of autonomic dysfunction. From these findings we postulated that patients who complain of dizziness are likely to have prolonged lag times that are a proxy for bladder neck dysfunction (BND). STUDY DESIGN: This was an Institute Review Board-approved study in which we enrolled new patients in a sequential fashion who were referred to our outpatient urology offices for evaluation of BBD over a 3-month period. All patients were asked if they frequently experienced dizziness when they rapidly stood from a sitting or lying down position or when they raised their head rapidly. An analysis of the following parameters was undertaken: prevalence of dizziness, bladder neck dysfunction, and comorbid psychiatric problems. Uroflowmetry findings were analyzed as well. RESULTS: Tilt-table group: In the tilt-table group the median age of the patients was 14.5 (4.5-18) years for the five males and five females who were tested. All males and four out of five females experienced a blood pressure drops of 20 mmHg or more on table tilting and three experienced syncope. All patients had prolonged lag times, with an average lag time of 16.5 s. All these patients were able to tolerate alpha-blockers once they were adequately hydrated and salt loaded. Alpha-blocker dosing was increased gradually. In the questionnaire group, 212 patients were initially enrolled: 125 girls and 87 boys. Eleven of 12 males and eleven of 16 females had prolonged lag times when dizziness was present. Sensitivity was 92% and 69%, specificity was 80% and 91% respectively for male and females. Analysis of the psychiatric history revealed a statistically significant association with dizziness and neuropsychiatric problems in the patients and family members. CONCLUSION: We have been able to show a high degree of sensitivity in male patients and a high degree of specificity in female patients that a simple question, "Do you get dizzy on rising in the morning or with rapid standing?", is a reliable marker for BND in children. We have also seen that there is an association between dizziness and psychiatric problems in patients and in family members. It appears from our results and the available literature that autonomic dysfunction is commonly associated with BND and dizziness can be a simple proxy question to identify this problem. PMID- 26875872 TI - Metabolic pathway of 3,6-anhydro-D-galactose in carrageenan-degrading microorganisms. AB - Complete hydrolysis of kappa-carrageenan produces two sugars, D-galactose and 3,6 anhydro-D-galactose (D-AnG). At present, however, we do not know how carrageenan degrading microorganisms metabolize D-AnG. In this study, we investigated the metabolic pathway of D-AnG degradation by comparative genomic analysis of Cellulophaga lytica LIM-21, Pseudoalteromonas atlantica T6c, and Epulopiscium sp. N.t. morphotype B, which represent the classes Flavobacteria, Gammaproteobacteria, and Clostridia, respectively. In this bioinformatic analysis, we found candidate common genes that were believed to be involved in D AnG metabolism. We then experimentally confirmed the enzymatic function of each gene product in the D-AnG cluster. In all three microorganisms, D-AnG metabolizing genes were clustered and organized in operon-like arrangements, which we named as the dan operon (3,6-d-anhydro-galactose). Combining bioinformatic analysis and experimental data, we showed that D-AnG is metabolized to pyruvate and D-glyceraldehyde-3-phosphate via four enzyme-catalyzed reactions in the following route: 3,6-anhydro-D-galactose -> 3,6-anhydro-D-galactonate -> 2 keto-3-deoxy-D-galactonate (D-KDGal) -> 2-keto-3-deoxy-6-phospho-D-galactonate -> pyruvate + D-glyceraldehyde-3-phosphate. The pathway of D-AnG degradation is composed of two parts: transformation of D-AnG to D-KDGal using two D-AnG specific enzymes and breakdown of D-KDGal to two glycolysis intermediates using two DeLey-Doudoroff pathway enzymes. To our knowledge, this is the first report on the metabolic pathway of D-AnG degradation. PMID- 26875873 TI - Genetic dissection of fruiting body-related traits using quantitative trait loci mapping in Lentinula edodes. AB - To provide a better understanding of the genetic architecture of fruiting body formation of Lentinula edodes, quantitative trait loci (QTLs) mapping was employed to uncover the loci underlying seven fruiting body-related traits (FBRTs). An improved L. edodes genetic linkage map, comprising 572 markers on 12 linkage groups with a total map length of 983.7 cM, was constructed by integrating 82 genomic sequence-based insertion-deletion (InDel) markers into a previously published map. We then detected a total of 62 QTLs for seven target traits across two segregating testcross populations, with individual QTLs contributing 5.5 %-30.2 % of the phenotypic variation. Fifty-three out of the 62 QTLs were clustered in six QTL hotspots, suggesting the existence of main genomic regions regulating the morphological characteristics of fruiting bodies in L. edodes. A stable QTL hotspot on MLG2, containing QTLs for all investigated traits, was identified in both testcross populations. QTLs for related traits were frequently co-located on the linkage groups, demonstrating the genetic basis for phenotypic correlation of traits. Meta-QTL (mQTL) analysis was performed and identified 16 mQTLs with refined positions and narrow confidence intervals (CIs). Nine genes, including those encoding MAP kinase, blue-light photoreceptor, riboflavin-aldehyde-forming enzyme and cyclopropane-fatty-acyl-phospholipid synthase, and cytochrome P450s, were likely to be candidate genes controlling the shape of fruiting bodies. The study has improved our understanding of the genetic architecture of fruiting body formation in L. edodes. To our knowledge, this is the first genome-wide QTL detection of FBRTs in L. edodes. The improved genetic map, InDel markers and QTL hotspot regions revealed here will assist considerably in the conduct of future genetic and breeding studies of L. edodes. PMID- 26875874 TI - The zinc cluster transcriptional regulator Asg1 transcriptionally coordinates oleate utilization and lipid accumulation in Saccharomyces cerevisiae. AB - In this study, we characterize a new function for activator of stress response genes (Asg1) in fatty acid utilization. Asg1 is required for full activation of genes in several pathways, including beta-oxidation (POX1, FOX2, and POT1), gluconeogenesis (PCK1), glyoxylate cycle (ICL1), triacylglycerol breakdown (TGL3), and peroxisomal transport (PXA1). In addition, the transcriptional activator Asg1 is found to be enriched on promoters of genes in beta-oxidation and gluconeogenesis pathways, suggesting that Asg1 is directly involved in the control of fatty acid utilizing genes. In agreement, impaired growth on non fermentable carbons such as fatty acids and oils and increased sensitivity to some oxidative agents are found for the Deltaasg1 strain. The lipid class profile of the Deltaasg1 cells grown in oleate displays approximately 3-fold increase in free fatty acid (FFA) content in comparison to glucose-grown cells, which correlates with decreased expression of beta-oxidation genes. The ?asg1 strain grown in glucose also exhibits higher accumulation of triacylglycerols (TAGs) during log phase, reaching levels typically observed in stationary phase cells. Altered TAG accumulation is partly due to the inability of the Deltaasg1 cells to efficiently break down TAGs, which is consistent with lowered expression of TGL3 gene, encoding triglycerol lipase. Overall, these results highlight a new role of the transcriptional regulator Asg1 in coordinating expression of genes involved in fatty acid utilization and its role in regulating cellular lipid accumulation, thereby providing an attractive approach to increase FFAs and TAGs content for the production of lipid-derived biofuels and chemicals in Saccharomyces cerevisiae. PMID- 26875875 TI - Changes in the soil microbial community after reductive soil disinfestation and cucumber seedling cultivation. AB - Reductive soil disinfestation (RSD) has been proven to be an effective and environmentally friendly way to control many soilborne pathogens and diseases. In this study, the RSDs using ethanol (Et-RSD) and alfalfa (Al-RSD) as organic carbons were performed in a Rhizoctonia solani-infected soil, and the dissimilarities of microbial communities during the RSDs and after planting two seasons of cucumber seedlings in the RSDs-treated soil were respectively investigated by MiSeq pyrosequencing. The results showed that, as for bacteria, Coprococcus, Flavisolibacter, Rhodanobacter, Symbiobacterium, and UC Ruminococcaceae became the dominant bacterial genera at the end of Al-RSD. In contrast, Et-RSD soil involved more bacteria belonging to Firmicutes, such as Sedimentibacter, UC-Gracilibacteraceae, and Desulfosporosinus. For fungi, Chaetomium significantly increased at the end of RSDs, while Rhizoctonia and Aspergillus significantly decreased. After planting two seasons of cucumber seedlings, those bacteria belonging to Firmicutes significantly decreased, but Lysobacter and Rhodanobacter belonging to the phylum Proteobacteria as well as UC Sordariales and Humicola belonging to Ascomycota alternatively increased in Al- and Et-RSD-treated soils. Besides, some nitrification, denitrification, and nitrogen fixation genes were apparently increased in the RSD-treated soils, but the effect was more profound in Al-RSD than Et-RSD. Overall, Et-RSD could induced more antagonists belonging to Firmicutes under anaerobic condition, whereas Al RSD could continuously stimulate some functional microorganisms (Lysobacter and Rhodanobacter) and further improve nitrogen transformation activities in the soil at the coming cropping season. PMID- 26875876 TI - Saturation mutagenesis on Arg244 of the tryptophan C4-prenyltransferase FgaPT2 leads to enhanced catalytic ability and different preferences for tryptophan containing cyclic dipeptides. AB - FgaPT2 from Aspergillus fumigatus catalyzes a Friedel-Crafts alkylation at C-4 of L-tryptophan and is involved in the biosynthesis of the ergot alkaloids fumigaclavines. Several tryptophan-containing cyclic dipeptides had also been prenylated by FgaPT2, but the turnover rate (k cat) was low. Here, we report the generation of FgaPT2 mutants by saturation mutagenesis at the amino acid residue Arg244 to improve its catalytic efficiency toward cyclic dipeptides. Thirteen mutated enzymes demonstrated up to 76-fold higher turnover number toward seven cyclic dipeptides than the non-mutated FgaPT2. More importantly, the mutated enzymes exhibited different preferences toward these substrates. This study provides a convenient approach for creation of new biocatalysts for production of C4-prenylated cyclic dipeptides. PMID- 26875877 TI - L-Rhamnose isomerase and its use for biotechnological production of rare sugars. AB - L-Rhamnose isomerase (L-RI, EC 5.3.1.14), catalyzing the isomerization between L rhamnose and L-rhamnulose, plays an important role in microbial L-rhamnose metabolism and thus occurs in a wide range of microorganisms. It attracts more and more attention because of its broad substrate specificity and its great potential in enzymatic production of various rare sugars. In this article, the enzymatic properties of various reported L-RIs were compared in detail, and their applications in the production of L-rhamnulose and various rare sugars including D-allose, D-gulose, L-lyxose, L-mannose, L-talose, and L-galactose were also reviewed. PMID- 26875878 TI - Impact of the freeze-drying process on product appearance, residual moisture content, viability, and batch uniformity of freeze-dried bacterial cultures safeguarded at culture collections. AB - In this study, causes of collapsed bacterial cultures in glass ampoules observed after freeze-drying were investigated as well as the influence of collapse on residual moisture content (RMC) and viability. Also, the effect of heat radiation and post freeze-drying treatments on the RMC was studied. Cake morphologies of 21 bacterial strains obtained after freeze-drying with one standard protocol could be classified visually into four major types: no collapse, porous, partial collapse, and collapse. The more pronounced the collapse, the higher residual moisture content of the freeze-dried product, ranging from 1.53 % for non collapsed products to 3.62 % for collapsed products. The most important cause of collapse was the mass of the inserted cotton plug in the ampoule. Default cotton plugs with a mass between 21 and 30 mg inside the ampoule did not affect the viability of freeze-dried Aliivibrio fischeri LMG 4414(T) compared to ampoules without cotton plugs. Cotton plugs with a mass higher than 65 mg inside the ampoule induced a full collapsed product with rubbery look (melt-back) and decreasing viability during storage. Heat radiation effects in the freeze-drying chamber and post freeze-drying treatments such as exposure time to air after freeze-drying and manifold drying time prior to heat sealing of ampoules influenced the RMC of freeze-dried products. To produce uniform batches of freeze dried bacterial strains with intact cake structures and highest viabilities, inserted cotton plugs should not exceed 21 mg per ampoule. Furthermore, heat radiation effects should be calculated in the design of the primary drying phase and manifold drying time before heat sealing should be determined as a function of exposure time to air. PMID- 26875879 TI - Homologous expression and biochemical characterization of the arylsulfatase from Kluyveromyces lactis and its relevance in milk processing. AB - The industrial manufacturing process of lactose-free milk products depends on the application of commercial beta-galactosidase (lactase) preparations. These preparations are often obtained from Kluyveromyces lactis. There is a gene present in the genome of K. lactis which should encode for an enzyme called arylsulfatase (EC 3.1.6.1). Therefore, this enzyme could also be present in beta galactosidase preparations. The arylsulfatase is suspected of being responsible for an unpleasant "cowshed-like" off-flavor resulting from the release of p cresol from milk endogenous alkylphenol sulfuric esters. So far, no gene/functionality relationship is described. In addition, no study is available which has shown that arylsulfatase from K. lactis is truly responsible for the flavor generation. In this study, we cloned the putative arylsulfatase gene from K. lactis GG799 into the commercially available vector pKLAC2. The cloning strategy chosen resulted in a homologous, secretory expression of the arylsulfatase. We showed that the heretofore putative arylsulfatase has the desired activity with the synthetic substrate p-nitrophenyl sulfate and with the natural substrate p-cresol sulfate. The enzyme was biochemically characterized and showed an optimum temperature of 45-50 degrees C and an optimum pH of 9-10. Additionally, the arylsulfatase was activated by Ca(2+) ions and was inactivated by Zn(2+) ions. Moreover, the arylsulfatase was inhibited by p-cresol and sulfate ions. Finally, the enzyme was added to ultra-heat treated (UHT) milk and a sensory triangle test verified that the arylsulfatase from K. lactis can cause an unpleasant "cowshed-like" off-flavor. PMID- 26875880 TI - Prospective investigation and literature review of tolerance dose on salivary glands using quantitative salivary gland scintigraphy in the intensity-modulated radiotherapy era. AB - BACKGROUND: The purpose of this study was to prospectively evaluate the scintigraphic results on patients who undergo intensity-modulated radiotherapy (IMRT) to investigate the tolerance doses for the salivary glands. METHODS: Salivary scintigraphy was performed on 35 patients with head and neck cancer before the beginning of radiotherapy (RT), and then at 6 weeks and again at 3 months after the completion of RT. Xerostomia was recorded according to the Radiation Therapy and Oncology Group (RTOG) grade. Salivary function was evaluated by calculating the excretion rate changes (DeltaF) for each salivary gland before and after RT. RESULTS: The parotid mean dose was significantly related to parotid DeltaF and the submandibular gland mean dose to the submandibular gland DeltaF. The parotid mean dose of 23 Gy was best correlated with the RTOG grades. The submandibular gland mean dose significantly related to DeltaF <=-50% and <=-75% was 42 Gy. CONCLUSION: The parotid mean dose of 23 Gy and the submandibular gland mean dose of 42 Gy is feasible for salivary function preservation in the IMRT era. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1746-E1755, 2016. PMID- 26875881 TI - The role of the antioxidant ascorbic acid in the elicitation of contact allergic reactions to p-phenylenediamine. AB - BACKGROUND: An allergic contact reaction is accompanied by high oxidative stress in the skin. Pretreatment of the skin with antioxidative substances could reduce the elicitation reaction. OBJECTIVES: To investigate, in a proof-of-principle study, whether pretreatment of the skin with the antioxidant ascorbic acid reduces the elicitation reaction to a p-phenylenediamine (PPD)-containing hair dye in sensitized subjects. METHODS: Twelve subjects with contact allergy to PPD, a documented skin reaction to a hair dye simulation exposure model and a history of hair dye-related skin complaints were included in this study. Skin areas on the forearms were, in a left versus right design, exposed to an emulsion with ascorbic acid and an emulsion without ascorbic acid, and then to a 2% PPD containing hair dye testing formulation. In addition, control areas were exposed to the emulsions and to the PPD-containing hair dye formulation without pretreatment. Skin reactions were graded on day (D)2 and D3. RESULTS: Pretreatment with ascorbic acid emulsion resulted in a reduction in the elicitation reaction in 7 of 12 subjects at D3 (p = 0.046). No statistically significant difference was observed at D2. CONCLUSIONS: Pretreatment of the skin with the antioxidant ascorbic acid had an attenuating effect on the elicitation reaction to PPD in sensitized individuals. PMID- 26875882 TI - Ovarian transposition in young women and fertility sparing. PMID- 26875883 TI - Cardiac magnetic resonance imaging in unusual form of hypertrophic cardiomyopathy. PMID- 26875884 TI - Autonomic nervous system and hypertension. PMID- 26875885 TI - Ulipristal acetate prior to in vitro fertilization in a female patient affected by uterine fibroids: a case report. AB - OBJECTIVE: Uterine leiomyomatosis and especially submucosal myomas hamper the outcomes of Assisted Reproductive Techniques (ART). Even though surgical treatment eliminates gross anatomical anomalies, medical treatment should be encouraged to improve the overall structure of the uterus, thereby enabling ART. CASE PRESENTATION: We report the case of an infertile female patient suffering from symptomatic uterine fibromatosis, who received 5 mg/day ulipristal acetate (UPA), a selective progesterone receptor modulator (SPRMs), for three months before and after hysteroscopic myomectomy. Uterine bleeding reduced on the eight days of treatment, with a subsequent improvement of pelvic pain. Under transvaginal ultrasound the uterus appeared globally enlarged with a diffuse leiomyomatosis of the myometrial layer. Saline infusion showed a markedly distorted cavity due two submucosal myomas (sized 31 * 24 mm and 21 * 19 mm, respectively) and one intramural myoma (37 * 34 mm). After three months the size of the myomas was reduced by 30-40%, allowing the hysteroscopic removal of the submucosal fibroids and the bigger intramural one. The smaller fibroids involving the myometrial layer were instead too diffused to be removed. At the conclusion of the subsequent cycle of UPA, the overall appearance of the cavity had improved, and the endometrial layer was regular, allowing the patient to undergo in vitro fertilization (IVF). There was no adverse effect related to treatment, and the endometrial biopsy did not reveal any histologic change. CONCLUSIONS: UPA seems to have a triple effect: it ensures prompt symptom relief, it reduces the size of the myomas enabling surgery and it improves the morphology of the uterus. PMID- 26875886 TI - A combined partially threaded cancellous lag screw for achieving maximum compressive force without compromising pullout strength. AB - OBJECTIVE: The partially threaded cancellous lag screw (PTLS) could not provide maximum compressive force (C(MAX)) for compression due to compromised pullout strength (POS). The combined partially threaded cancellous lag screw (CPTLS) could provide higher C(MAX) than PTLS. However, the change of POS at the point of C(MAX) when using CPTLS for compression has never been explored. The aim of this study was to determine whether POS decreased at the point of C(MAX) during CPTLS compression for different bone mineral densities (BMDs). MATERIALS AND METHODS: Three synthetic cancellous bone blocks were used for this study, and the BMDs were 0.12 g/cm3, 0.16 g/cm3, and 0.20 g/cm3, respectively. 20 pilot holes with 3.2 mm diameters were prepared equably in each block. A CPTLS was inserted through the custom-designed measuring device into a pilot hole manually until failure for measuring C(MAX), and the pullout test was done with the identical CPTLS for measuring POS. RESULTS: The C(MAX) and POS of the CPTLS were not significantly different in the three specimens, and the ratios of the mean C(MAX) to the mean POS were very similar in the three specimens (0.98 in the 0.12 g/cc specimen, 1.01 in the 0.16 g/cc specimen and 0.98 in the 0.20 g/cc specimen). CONCLUSIONS: C(MAX) is achieved without a decrease in POS during CPTLS compression independent of the BMD. PMID- 26875887 TI - The curative efficacy of arthroscopic therapy in treating anterior cruciate ligament rupture with secondary osteoarthritis. AB - OBJECTIVE: To compare and analyze the clinical effects of arthroscopic therapy and drug therapy in treating anterior cruciate ligament (ACL) rupture with secondary osteoarthritis (OA). PATIENTS AND METHODS: A total of 68 patients that were diagnosed as ACL rupture with secondary OA in our hospital from February 2014 to February 2015 were enrolled in our study. All of the patients were randomly divided into control group (n = 30) and observation group (n = 38) according to the order of admission. The patients in the control group were given analgesic, anti-inflammatory drugs + functional rehabilitation training whereas the patients in the observation group were given ACL reconstruction + OA debridement and functional rehabilitation training under arthroscopy. RESULTS: The success rate of the observation group was 92.1%. After 3-month follow-up, the clinical total effective rate of the observation group was significantly higher than that of the control group, the prevalence of complications in the observation group was significantly lower than in the control group, and differences were statistically significant (p < 0.05). Lysholm scale scoring of observation group was significantly higher than of the control group, modified McGill pain scale score was significantly lower than that of the control group, and differences were statistically significant (p < 0.05). Quadriceps muscle peak torque, average power, and the optimal single work at 60 degrees /s, 120 degrees /s, and 180 degrees /s were significantly higher than those of the control group, and differences were statistically significant (p < 0.05). CONCLUSIONS: Arthroscopic operative therapy was safe and effective for the treatment of ACL with secondary OA. Compared with drug therapy, it can significantly improve the movement function of the knee joint, so it was worthy of clinical application. PMID- 26875888 TI - Descriptive epidemiology of clubfoot in Romania: a clinic-based study. AB - OBJECTIVE: Congenital clubfoot affects 1 per 1000 live births per year in Romania. To date, no epidemiological studies have been conducted in this country to assess risk factors associated with the deformity. The aim of this study was to evaluate specific environmental and socio-demographic factors that may increase the risk of an infant to be born with clubfoot. PATIENTS AND METHODS: A descriptive clinic-based study over a twelve-week period was conducted using structured questionnaires given to biological parents of clinically confirmed clubfoot and control subjects. 62 parents of probands and 66 parents of control patients were enrolled for risk factor questionnaires. Phenotypic data from clubfoot children was also collected. RESULTS: We found that males were twice as likely to have clubfoot and half of clubfoot subjects were affected bilaterally. There was no significant difference in the rate of left versus right clubfoot. Infant and maternal characteristics showing a strong association with clubfoot included breech presentation and old maternal age at conception. CONCLUSIONS: Our results support reported literature data that males are two times as likely to have clubfoot which indicates a genetic influence. Previous reports suggest clubfoot babies are born to young mothers but in Romania advanced maternal age (>= 35 years) was an indicator which may suggest genetic influence. This clinic based study does not support previously recorded data of a positive association for maternal or household smoking. Data from this Romanian population also does not support previous data suggesting strong associations with maternal diabetes. PMID- 26875889 TI - Efficacy of 3.6% topical ALA-PDT for the treatment of severe acne vulgaris. AB - OBJECTIVE: To evaluate the efficacy and safety of topical 5-aminolevulinic acid (ALA) mediated photodynamic therapy (PDT) for the treatment of severe acne vulgaris. PATIENTS AND METHODS: A total of 125 patients with Pillsbury III-IV severe facial acne were treated with 3 courses of ALA-PDT with an interval of 2 weeks. ALA gel (3.6%) was applied topically to acne lesions for 1.5 h. The lesions were irradiated by a LED light of 633 nm with a light intensity of 66 mW/cm2 and a light dose of 126 J/cm2. Patients were evaluated for efficacy and safety at weeks 2, 4, 6, 8, 12 after the initial treatment. RESULTS: The total effective rates were 1.6%, 24.8%, 68.8%, 89.6% and 88.8% at the 2- 4- 6- 8- and 12-week after the initial treatment respectively. The clinical outcomes were the best at 4 weeks after the final treatment. The best effective rate and cure rate were 89.6% and 44% respectively. 26 patients and 16 patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment respectively, but all of them showed good or excellent improvement after 3-course treatment. Adverse reactions were mild and transient. CONCLUSIONS: 3.6% ALA-PDT is a simple, safe and effective therapeutic option for the treatment of severe acne vulgaris. PMID- 26875890 TI - Combination therapy with hydrogen peroxide (4%), salicylic acid (0.5%) and D panthenol (4%): efficacy and skyn tolerability in common acne vulgaris during sun exposure period. AB - OBJECTIVE: Acne vulgaris is a disease of the sebaceous follicle which affects up to 90% of adolescent patients. Topical retinoids, benzoyl peroxide and antibiotics are the main treatments for mild to moderate acne vulgaris. The use of such topical treatments is often associated with local irritation and dryness making the skin more sensitive to the sun. The aim of our study was to assess the efficacy and skin tolerability of a fixed-dose combination therapy with hydrogen peroxide (4%), Salicylic acid (0.5%) and D-panthenol (4%) (HSD) gel, in mild moderate acne vulgaris, during the period of sun exposure. PATIENTS AND METHODS: We retrospectively observed 30 patients of Central Italy with mild to moderate acne between April and September 2012. All the patients selected underwent only therapy with HSD gel once a day in the evening for 60 days, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. RESULTS: The mean GES value showed a statistically significant reduction: 2.03 (SD 0.81) at baseline, 1.63 (SD 0.81) and 0.90 (SD 0.71) respectively at 30 and 60 days (p < 0.01). 21 (70%) and 27 patients (90%) did show good or very good tolerability at 30 and 60 days respectively. CONCLUSIONS: Topical treatments with retinoids, antibiotics and antiseptics may increase skin irritation reducing patient adherence to the treatment. HSD gel has shown a good skin tolerability and efficacy in reducing acne lesions, even during the sun exposure period in which traditional treatments should be cautiously used. PMID- 26875891 TI - Association of ABO and Rh blood groups with type 2 diabetes mellitus. AB - OBJECTIVE: The phenotypic "ABO" blood groups are inherited antigenic substances which are found on the surface of red blood cells in addition to other tissues. Certain hypothesis advocates that genetic predisposition like "ABO" blood group would be associated with occurrence of diseases including type 2 diabetes. This study aimed to investigate the potential association between "ABO" and "Rhesus" blood groups with type 2 diabetes. MATERIALS AND METHODS: We identified 47 research documents in a data based search including ISI-Web of Science, EMBASE and PubMed. Literature was explored using the key terms including "ABO blood groups" "type 2 diabetes". Studies in which "ABO" blood types and diabetes mellitus were discussed included without restrictions of research documents, types, status and language of the publications. Finally, 15 publications which matched our criteria were included, and remaining studies were excluded. RESULTS: Blood group "B" was associated with high incidence of type 2 diabetes and blood group "O" has a minimum association with type 2 diabetes. Blood group "A" and "AB" were almost equally distributed in both diabetic and non-diabetic population. However, we were unable to find an association between "Rh+ve" and "Rh-ve" blood groups with type 2 diabetes. CONCLUSIONS: Subjects with blood group "B" are at high risk while individuals with blood group "O" are at low peril of evolving type 2 diabetes. It is suggested that subjects with blood group "B" should be closely monitored by physicians as these subjects have an increased risk of type 2 diabetes. PMID- 26875892 TI - Clinical significance of serum protease activated receptor1 levels in patients with lung cancer. AB - OBJECTIVE: Protease-activated receptors (PAR) are G protein coupled receptors and they regulate many biological processes, including coagulation and cell survival and they might be good markers in some types of malignant tumors, providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of PAR1 in lung cancer patients. PATIENTS AND METHODS: Eighty patients with lung cancer were enrolled into this study. Serum PAR1 levels were determined by the solid-phase sandwich ELISA method. Median age was 58.5-years old, range 36 to 80 years. RESULTS: The majority of the patients had NSCLC (85%) and stage IV disease (56%). The baseline serum PAR1 concentrations of the lung cancer patients were significantly higher than control group (median values 26.45 ng/mL v 0.07 ng/mL, p < 0.001). However, clinical variables including age, gender, histology, stage of disease, and response to chemotherapy were not found to be correlated with serum PAR1 levels (p > 0.05). Moreover, it failed to show any prognostic value on the survival of the lung cancer patients. CONCLUSIONS: The serum levels of PAR1 might have a diagnostic value in lung cancer patients. However, its predictive and prognostic values were not determined. PMID- 26875893 TI - Interleukin-17A inhibits cell autophagy under starvation and promotes cell migration via TAB2/TAB3-p38 mitogen-activated protein kinase pathways in hepatocellular carcinoma. AB - OBJECTIVE: Hepatocellular carcinoma (HCC) is characterized by progressive development and poor prognosis against a background of chronic inflammation. Interleukin (IL)-17A is an important proinflammatory cytokine that contributes to inflammatory pathology and tumor microenvironment. Research on autophagy has increasingly focused on its role in inflammation. Thus, we investigated the effect of IL-17A on the progression of HCC through the autophagic pathway. MATERIALS AND METHODS: The expression and prognostic values of IL-17A and autophagic gene Beclin-1 were determined using immunohistochemistry in 83 HCC patients after resection. The effects and underlying molecular mechanisms of IL 17A on human HCC were explored in vitro using recombinant human IL-17A. RESULTS: High expression of IL-17A and low expression of Beclin-1 were associated with worse TNM stage in HCC patients. And the level of autophagy was lower in tumor tissues compared with tumor-adjacent tissues. In vitro, recombinant human IL-17A inhibited starvation-induced autophagy and maintained cell viability through activating TAK1-binding protein 2 (TAB2 and TAK1-binding protein 3 (TAB3) inducing p38 mitogen-activated protein kinase (MAPK) in Huh7 and HepG2 HCC cells. IL-17A promoted migration of HCC cells through the TAB2/p38 MAPK and TAB3/p38 MAPK pathways. CONCLUSIONS: IL-17A promotes migration of HCC cells and prevents autophagic cell death from starvation by activating TAB2/p38 MAPK and TAB3/p38 MAPK. PMID- 26875894 TI - Clinical analysis on argon plasma coagulation (APC) under painless colonoscopy for treatment of patients with colorectal polyp canceration. AB - OBJECTIVE: To investigate the clinical effects of argon plasma coagulation combined high frequency electric knife in treating patients with colorectal polyp canceration. PATIENTS AND METHODS: 56 patients diagnosed with colorectal polyp canceration were divided into control group (n=23) and observation group (n=33). Patients in the control group were treated with high frequency electric band ligation electroexcision while patients in observation group were treated with argon coagulation combined high frequency electric knife therapy. The patients were followed up for 6 months and, then, compared for their clinical effects and prognosis. RESULTS: The average diameter of the polyp, the ratios of sessile and flat polyps in observation group were significantly higher than those in the control group with p<0.05. While the differences in the ratio of adenomatous polyp, middle and high differentiated as well as leafless polyps between the two groups had no statistical significance with p>0.05. Further, the differences in operation completion rate and polyp resection rate at one time in observation group was significantly higher than those of control group while operative complication rate and operation time was significantly lower than those in the control group with p<0.05. Also, the differences in recurrence in situ and recurrence time did not differ significantly between the two groups. CONCLUSIONS: Treating colorectal polyps by argon plasma coagulation combined high frequency electric knife could extend polyp resection indication, along with improvement in the operation effect and reduction of complications. PMID- 26875895 TI - MiR-874 inhibits cell growth and induces apoptosis by targeting STAT3 in human colorectal cancer cells. AB - OBJECTIVE: MicroRNA-874 (miR-874) has previously been identified as a tumor suppressor in several cancers. However, its role in colorectal cancer (CRC) has not been studied. In the present study, we aimed to investigate its potential roles in regulating cell growth and apoptosis in human CRC cells. PATIENTS AND METHODS: MiR-874 expression was detected by real-time PCR analysis. Cell viability was detected by CCK-8 assay. Protein expression level was detected by Western blot, and luciferase activity assay was used to validate the interaction between mir-874 and STAT3 mRNA 3'UTR. RESULTS: We found that miR-874 was significantly downregulated in CRC tissues. Gain and loss of function of miR-874 proved that miR-874 could inhibit cell growth and induce apoptosis in CRC cells. Luciferase reporter assay and Western blot analysis showed that miR-874 repressed STAT3 expression by targeting its mRNA 3'UTR. Silencing STAT3 recapitulated the phenotype of miR-874 overexpression. Moreover, the inverse correlation between miR-874 expression and STAT3 expression was validated in CRC specimens. CONCLUSIONS: These data demonstrate that miR-874 functions as a tumor suppressor by repression of STAT3, suggesting its potential therapeutic value in CRC treatment. PMID- 26875896 TI - Whole genome sequencing identified new somatic mutations for chronic myelomonocytic leukemia. AB - OBJECTIVE: We aimed to gain new insight into the molecular alterations of Chronic Myelomonocytic Leukemia (CMML). PATIENTS AND METHODS: We performed whole-genome sequencing (WGS) and subsequent Sanger sequencing validation analysis in three individuals with CMML. Genomic DNA samples from bone marrow and matching buccal mucosa samples were sequenced. RESULTS: For all six samples, a total of 806.43 Gb data were generated, achieving a minimum mean depth of 30.76. A total of 22 somatic variants were found to be protein-altering, including 1 exonic frame shift indel, 18 missense SNVs, 2 stop gain SNVs, and 1 stop loss SNV. We focused on the five novel variants which have not been reported in known databases and successfully validated three missense SNVs in AKAP4, COL2A1, and MAML1, respectively. CONCLUSIONS: WGS analyzes provided us a new insight into the molecular events governing the pathogenesis of CMML. The somatic variants we reported here may provide new targets for further therapeutic studies. PMID- 26875897 TI - Laparoscopic treatment experience of severe acute pancreatitis complicated by peptic ulcer perforation. AB - OBJECTIVE: To explore the clinical effect of emergency laparoscopic repair of perforation and conventional open surgery in the treatment of severe acute pancreatitis (SAP) complicated with peptic ulcer perforation. PATIENTS AND METHODS: A total of 34 patients diagnosed as severe acute pancreatitis complicated by peptic ulcer perforation were selected as experimental group and a total of 38 patients diagnosed as severe acute pancreatitis complicated by peptic ulcer perforation were selected as control group. The experimental group was treated with emergency laparoscopic perforation repair and the control group was treated with conventional open operation, comparing the difference between the results and the prognosis of the patients. RESULTS: The success rate of the experimental group and the control group are compared was not statistically significant (p > 0.05). While the operation time, postoperative intestinal function recovery time, the time of drainage tube pulled out and the occurrence of complications in experimental group was significantly lower than those in control group. The survival rate of the experimental group was significantly higher than that of the control group, the recurrence rate was significantly lower than that of the control group (p < 0.05). The high sensitive C reactive protein (hs CRP) and tumor necrosis factor TNF-alpha levels of the experimental group were significantly lower than those of the control group (p < 0.05). CONCLUSIONS: Emergency laparoscopic repair of peptic ulcer perforation in the treatment of SAP complicated with perforation is safe and effective, which can reduce the systemic inflammatory response and better than conventional open surgery. PMID- 26875898 TI - The correlation between Doppler US measurement of hepatic arterial flow and the MELD score in patients with chronic liver disease. AB - OBJECTIVE: The aim of the study was to determine the relationship between the Model for End-Stage Liver Disease (MELD) score and hepatic arterial hemodynamic parameters measured via Doppler US. PATIENTS AND METHODS: Etiologic causes and hepatic artery hemodynamic parameters of 121 patients with chronic liver parenchymal disease were compared with MELD scores. Doppler ultrasonography (US) was used to assess flow velocity, pulsatility index (PI) and resistance index (RI) in the hepatic artery (HA). Each patient's MELD scores were calculated at the time of Doppler ultrasound performed. RESULTS: There was statistically significant difference between MELD score and hepatic artery RI value (p < 0.001, r = 0.616). This difference was statistically more significant in the group which consisted of multiple etiologic causes (p < 0.001, r = 0.837). CONCLUSIONS: We found significant relation between MELD score and hepatic artery RI measurements in patients with chronic liver parenchymal disease. PMID- 26875899 TI - High dose amoxicillin-based first line regimen is equivalent to sequential therapy in the eradication of H. pylori infection. AB - OBJECTIVE: Helicobater (H.) pylori eradication rates with standard first-line triple therapy have declined to unacceptable levels. To date, amoxicillin resistant H. pylori strains have rarely been detected. Whether increasing the dosage of amoxicillin in a standard 7 days eradicating regimen may enhance its efficacy is not known. The aim of this paper is to compare the efficacy of a 7 days high-dose amoxicillin based first-line regimen with sequential therapy. PATIENTS AND METHODS: We have retrospectively analyzed data from 300 sex and age matched patients, who underwent 3 different therapeutic schemes: (1) standard LCA, lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg bid for 7 days; (2) high dose LCA (HD-LCA), lansoprazole 30 mg bid, clarithromycin 500 mg bid and amoxicillin 1000 mg tid for 7 days; (3) sequential LACT, lansoprazole 30 mg bid plus amoxicillin 1000 mg bid for 5 days, followed by lansoprazole 30 mg bid, clarithromycin 500 mg bid and tinidazole 500 mg bid for 5 days. Eradication was confirmed by 13C-urea breath test. Compliance and occurrence of adverse effects were also assessed. RESULTS: Eradication rates were: 55% for LCA, 75% for HD-LCA and 73% for LACT. Eradication rates were higher in HD-LCA group compared to LCA (p<0.01), while no significant differences were observed in HD-LCA group compared to LACT (p=ns). Compliance and occurrence of adverse effects were similar among groups. CONCLUSIONS: High-dose amoxicillin based eradicating treatment is superior to standard triple therapy and equivalent to sequential therapy; compared to the latter, the shorter duration may represent an advantage. PMID- 26875900 TI - Acute coronary syndrome and platypnoea-orthodeoxia with thoracic and interauricular septal aneurysms. AB - OBJECTIVE: Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea induced by the upright position and relieved by supine position and an arterial deoxygenation increased by the upright position which improves during recumbency. Several anatomical factors that can alter the atrial anatomy and facilitate shunting through an interatrial defect have been related to this syndrome. In many cases, this syndrome has been associated with patent foramen ovale (PFO) and right-to-left shunt. Rarely platypnea-orthodeoxia syndrome has been described associated with an aortic and with an interauricular septal aneurysm too. CASE PRESENTATION: We present a case of platypnea-orthodeoxia syndrome in a 85-year old woman with patent foramen ovale, interauricular septal aneurysm and ascending aortic aneurysms who was admitted for an acute coronary syndrome which could be of embolic origin and was responsible for ventricular fibrillation during the transfer to the hospital. PFO closure was performed by percutaneous device and right coronary artery obstruction was treated by transluminal angioplasty and stenting. PMID- 26875901 TI - The clinical research of off-pump coronary artery bypass grafting by small incision at the left chest. AB - OBJECTIVE: To explore the clinical value of off-pump coronary artery bypass grafting by small incision at the left chest, and develop a better surgical regimen for coronary heart disease patients. PATIENTS AND METHODS: 201 coronary heart disease patients who need coronary artery bypass grafting were required and randomly divided into 2 groups including a control group and an observation group. There were 107 cases in the control group who received coronary bypass grafting by extracorporeal circulation; there were 103 cases in the observation group who received off-pump coronary bypass grafting by small incision at the left chest. The duration of the mechanism ventilation, length of stay in ICU, hospitalization time, postoperative drainage volume, and the occurrence rate of complications were recorded and compared. RESULTS: The duration of mechanism ventilation, length of stay in ICU, hospitalization time and postoperative drainage volume in the control group were (19.21 +/- 1.33) hours, (5.08 +/- 0.57) days, (21.20 +/- 2.34) days and (997.68 +/- 96.35) mL, which were (7.73 +/- 0.74) hours, (2.83 +/- 0.16) days, (15.67 +/- 1.18) days and (901.53 +/- 89.32) mL in the observation group respectively, with statistical difference between the two groups (p<0.05). The occurrence rates of renal insufficiency and arrhythmia were both 6.54% and 0.97% in the control group and the observation group, respectively. The occurrence rates of postoperative renal insufficiency and arrhythmia in the observation group were both significantly lower than those in the control group, with statistical significance analysis (p < 0.05). Postoperative low cardiac output, second thoracotomy, cerebrovascular disease, pulmonary infection, perioperative cardiac infarction and mortality did not display a significant difference between the two groups (p > 0.05). CONCLUSIONS: Off-pump coronary artery bypass grafting by small incision at the left chest is a surgical method with less injury and fast recovery, which can be used as the preferred therapeutical method for the coronary heart disease patients who need coronary artery bypass grafting. PMID- 26875902 TI - Study of a novel coating strategy for coronary stents: evaluation of stainless metallic steel coated with VEGF and anti-CD34 antibody in vitro. AB - OBJECTIVE: To access the cytotoxicity and the effect on the endothelial progenitor cell (EPC) differentiation of stainless steel sheets simultaneously coated with VEGF and anti-CD34 antibody. MATERIALS AND METHODS: 316L stainless steel sheets (diameter 6 mm, thickness 1 mm) were divided into the D-H (Bare metal), D-(H-V)10 (VEGF-coated metal) and D-(H-V)10-A (VEGF and anti-CD34 antibody co-coated metal) groups. The cytotoxicity effect of the three groups was measured using MTT assay. Percentage of EPC positive for CD34, CD133 and KDR were detected by flow cytometric assay. Endothelial cells positive for CD31 and VE Cadherin were also detected by flow cytometric assay. RESULTS: The percentages of isolated cells positive for CD133, CD34 and KDR were 89.9%, 91.3%, and 90.4%, respectively, suggesting that the EPCs were successfully isolated. MTT results showed that the stainless steel sheets coated with VEGF and anti-CD34 antibody have less toxicity on seeded EPCs than single VEGF coating or bare metal. We further found that with VEGF and anti-CD34 antibody co-coating could significantly promote the differentiation of EPCs in vitro when compared with that of single VEGF coating and bare metal. CONCLUSIONS: Our study provided a preliminary evaluation of metallic steel sheet coated with VEGF and anti-CD34 antibody in vitro. Our findings suggest that simultaneously coating the stents with VEGF and anti-CD34 antibody might be a novel research direction for facilitating re-endothelialization in order to reduce ISR after stent implantation. PMID- 26875903 TI - Impact of QRS morphology on heart rate turbulence and heart rate variability after cardiac resynchronization therapy in patients with heart failure. AB - OBJECTIVE: Impairment of heart rate turbulence (HRT) and heart rate variability (HRV) are associated with poor prognosis in chronic heart failure (CHF). Although previous studies have demonstrated that patients with a left bundle branch block (LBBB) have a better outcome with cardiac resynchronization therapy (CRT), the effect of QRS morphology on HRV and HRT is not known. We aimed to evaluate the effect of QRS morphology on HRV and HRT after CRT implantation in patients with CHF. PATIENTS AND METHODS: Patients who had been implanted a CRT device with cardioversion-defibrillation feature were included to the study. Forty-three patients with LBBB (group 1) were compared with 21 patients without LBBB (group 2). HRV and HRT parameters were compared before and one month after CRT implantation. RESULTS: We compared the echocardiographic and electrocardiographic changes in both groups after CRT. Cardiac output (CO) was found to be significantly much more increased in group 1 (1.1 +/- 0.4 vs. 0.6 +/- 0.4, p = 0.001). Similarly, except SDNN and LF, all HRT and HRV parameters were significantly changed in the patients with LBBB (TO 1.4 +/- 0.3 vs. 1.2 +/- 0.2, p = 0.001; TS -1.8 +/- 0.7 vs. -0.9 +/- 0.7, p = 0.001; RMSSD -15.7 +/- 9.9 vs. 6.3 +/- 6.2, p = 0.001; PNN50 -7.0 +/- 4.6 vs. -1.7 +/- 1.1, p = 0.001; HF -13.3 +/- 6.7 vs. -4.3 +/- 3.5, p = 0.001; LF/HF 1.9 +/- 0.4 vs. 1.5 +/- 0.2, p = 0.001) compared to those without LBBB. Lineer regression analysis showed that the CO (beta = 0.2, t = 2.8, p = 0.007) and QRS configuration (beta = 0.6, t = 0.5, p = 0.001) were independent parameters affecting TO. CONCLUSIONS: HRV and HRT are improved after CRT but these improvements are more remarkable in patients with LBBB. CO, QRS configuration (but not duration) were two independent parameters affecting TO, LF and LF/HF ratio after CRT. PMID- 26875904 TI - Plasma microRNA-21 is a potential diagnostic biomarker of acute myocardial infarction. AB - OBJECTIVE: Previous studies have demonstrated that microRNA-21 (miR-21) is involved in the pathogenesis of myocardium infarction and cardiac fibrosis; the present study aimed to investigate its potential role in the diagnosis of acute myocardium infarction (AMI). PATIENTS AND METHODS: A cohort of patients with AMI and angina pectoris (AP) were studied, plasma miR-21 level was determined by Realtime-PCR. RESULTS: We found that the plasma miR-21 level was significantly elevated in patients with AMI compared with those with AP or healthy people. Further studies demonstrated the correlation of miR-21 and several traditional markers such as creatine kinase (CK), creatine kinase-MB (CK-MB) and troponin I (cTnI) in study subjects. Finally, receiver-operator characteristic curve (ROC) analysis showed that miR-21 has similar diagnostic ability compared with CK, CK MB and cTnI. CONCLUSIONS: Plasma miR-21 may be a novel biomarker for the diagnosis of AMI. Our study may also provide implications for the development of new biomarkers. PMID- 26875905 TI - Cardiac shock wave therapy shows better outcomes in the coronary artery disease patients in a long term. AB - OBJECTIVE: Almost all the past CSWT studies show the beneficial effects on CAD patients in a maximum duration of 1-year follow-up. The aim of this study was to evaluate the actual CSWT effects in 6 years follow-up period. PATIENTS AND METHODS: The subjects were selected exclusively on the basis of inclusion criteria. The total number of patients was 52, out of which control group (n = 11) and the shock wave group (SW group, n = 41) was selected. RESULTS: The wall motion, MPI, nitrate dosage, NYHA classification, SAQ scores, CCS grading, 6 MWT were markedly improved in the long-term (6 years) follow-up for SW group than the control group. CONCLUSIONS: Following 6 years of follow-up, the CSWT provided agreeable results that improved myocardial function and quality of life in comparing to the month 0 and the control group. These outcomes advise that on a long-term (72 months) CSWT shows better parameters than the control group. These findings highlight that CSWT can improve clinical symptoms, morphology, functions of the heart and quality of life in patients with CHD than the patients just on drug therapy for a long-term. PMID- 26875906 TI - Effect of bedtime dosing of barnidipine hydrochloride in non-dipper hypertensive patients with obstructive sleep apnoea not treated with continuous positive airway pressure. AB - OBJECTIVE: Obstructive sleep apnoea (OSA) is considered a cause of secondary hypertension. About 50% of patients with OSA show elevated blood pressure levels. Non-dipper pattern (blunted or absent nocturnal decrease of blood pressure) is frequently observed in patients with OSA and is associated with increased cerebral, cardiovascular and renal events. The aim of this study was to observe the effect of barnidipine calcium channel blocker on these patients. PATIENTS AND METHODS: Forty-one patients (mean age 69 +/- 17 years, 18 females) with previously diagnosed OSA (by reduced channel home-based polysomnography) who were not being treated with continuous positive airway pressure (CPAP) because of contraindications or because of patient intolerance or rejection were evaluated. Non-dipper status was defined as the presence of a nighttime fall in systolic blood pressure (BP) which was < 10% that of daytime systolic BP as observed in a previous ambulatory blood pressure (ABP) monitoring. OSA was defined according to the presence of 5 or more episodes per hour of apnoea, hypopnoea or arousal due to respiratory effort. The reproducibility of non-dipping status was confirmed through a second 24-h ABP monitoring performed at baseline. On top of the previous stable treatment regimen (which excluded calcium-channel blockers), a 10 mg dosing of barnidipine hydrochloride at bedtime was added to all subjects during a 12-week period. RESULTS: Among the 41 non-dipper patients, 32 (78%) showed complete normalization of circadian rhythm. Add-on treatment with barnidipine was generally well tolerated. CONCLUSIONS: Bedtime dosing of the calcium-channel blocker (CCB) barnidipine significantly reduced mean nighttime systolic and diastolic ABP in hypertensive patients presenting with non-dipper pattern and OSA--not on CPAP treatment. Moreover, it restored the previously altered circadian rhythm in the majority of them. PMID- 26875907 TI - Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling. AB - OBJECTIVE: Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a beta-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. RESULTS: Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. CONCLUSIONS: Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down regulating galectin-3 signal pathway. PMID- 26875908 TI - High-volume hemofiltration combined with early goal-directed therapy improves alveolar-arterial oxygen exchange in patients with refractory septic shock. AB - OBJECTIVE: This study is to evaluate the effect of high-volume hemofiltration (HVHF) and early goal-directed therapy (EGDT) on alveolar-arterial oxygen exchange in patients with refractory septic shock. PATIENTS AND METHODS: Patients were classified into two groups by a prospective cohort study: 86 received both HVHF and EGDT (the HVHF group), and 81 treated with EGDT only (the control group). Alveolar-arterial oxygen pressure was taken at baseline and at days 1, 3, and 7, and respiratory index (RI, ratio of P(a)O2 alveolar-arterial oxygen pressure difference (P(A-a)DO2) to arterial oxygen pressure (P(a)O2) was calculated. RESULTS: At day 7, the levels of central venous and arterial blood oxygen content were significantly higher in the HVHF vs. the control group (both with p < 0.05). The level of oxygen extraction ratio (O2ER) was significantly higher in the HVHF than the control group (p < 0.01). The levels of P(A-a)DO2 and RI were significantly lower in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). RI and the ratio of P(a)O2 to the fraction of inspired oxygen were significantly higher in the HVHF than the control group (p < 0.05 and p < 0.01, respectively). The acute physiology and chronic health evaluation score and the sequential organ failure assessment score in the HVHF group were significantly lower compared to the control group (p < 0.01 and p < 0.05, respectively). At day 28, the mortality rate was lower in the HVHF vs. the control group (p < 0.01). CONCLUSIONS: These findings demonstrated that HVHF, when used as an adjunctive therapy to the EGDP protocol, could improve alveolar arterial oxygen exchange, clinical outcome and survival in patients with refractory septic shock. PMID- 26875909 TI - Comparative effects of Quercetin and SRT1720 against D galactosamine/lipopolysaccharide-induced hepatotoxicity in rats: biochemical and molecular biological investigations. AB - OBJECTIVE: Quercetin, a plant flavonoid with potent antioxidant action, has been shown to be ameliorative against different types of liver insults, including D Galactosamine/Lipopolysaccharide (D-GalN/LPS). The notion that its cytoprotective effects are SIRT1 mediated is still controversial. In this work, we examined whether the synthetic allosteric SIRT1 activator, SRT1720, may similarly attenuate D-GalN/LPS-induced hepatotoxicity. MATERIALS AND METHODS: Male Wistar rats were randomly assigned into 6 groups: (1) Control, (2) Quercetin, (3) SRT1720, (4) D-GalN/LPS, (5) Quercetin + D-GalN/LPS and (6) SRT1720 + D-GalN/LPS. After twenty-four hours, the effects of these treatments were evaluated by biochemical studies, real-time PCR and Western blot. RESULTS: D-GalN/LPS treatment downregulated SIRT1 expression and markedly increased the aminotransferase, bilirubin and conjugated diene levels. Conversely, quercetin and SRT1720 pretreatments upregulated SIRT1 expression and decreased the levels of the aforementioned markers. Quercetin had more profound effect on SIRT1 expression than SRT1720. Moreover, quercetin was more efficacious than SRT1720 in combatting the cytotoxic effects of D-GalN/LPS, as evidenced by lower markers of liver injury. CONCLUSIONS: These results strongly suggest the involvement of SIRT1 in the cytoprotective effects of quercetin and SRT1720 against D-GalN/LPS induced hepatotoxicity. PMID- 26875910 TI - Assessment of the analgesic, anti-inflammatory and sedative effects of the dichloromethanol extract of Schinus molle. AB - OBJECTIVE: Determination of the active fraction and compounds of the dichloromethanol extract of Schinus molle seeds and evaluation of their biological effects. MATERIALS AND METHODS: Dried seeds of Schinus molle were sequentially extracted in hexane, acetyl acetate and dichloromethane. The dichloromethane extract was separated into two fractions (1 and 2) by column chromatography. Fraction 2 was further separated into its two constituent compounds which were characterized as belonging to the lanosteroid group of compounds. Both factions were tested for their analgesic, anti-inflammatory and sedative effects. RESULTS: The two fractions significantly increased (p<0.05) the tail flick latency though fraction 2 provided better and more long lasting protection against thermal pain. On the other hand, the anti-inflammatory effect of ibuprofen, though inferior to the anti-inflammatory effect of fraction 2 was better than the effects of fraction 1. Fraction 2 significantly (p<0.01) reduced rat paw oedema compared to the saline treatment group throughout the experiments while fraction 2 compared to fraction 1 showed significantly (p<0.01) greater inflammatory effects. On the other hand both fractions lacked significant sedative effects. CONCLUSIONS: Given that fraction 2 had only two constituent compounds (isomasticadienonic and Masticatrienonate), one or both of these compounds should be contributing to the observed analgesic and anti-inflammatory effects. PMID- 26875911 TI - Newer antifungal agents micafungin and voriconazole for fungal infection prevention during hematopoietic cell transplantation: a meta-analysis. AB - OBJECTIVE: The new antifungal agents provide further opportunities for effective prophylaxis for fungal infections during stem cell transplantation for patients with hematologic malignancies; however, the efficacy of these antifungal prophylactic drugs has not yet been established. This study was to compare the newer antifungal agents micafungin and voriconazole for prophylaxis effects on the clinical outcomes. MATERIALS AND METHODS: We electronically searched the database of Cochrane Central Register of Controlled Trials, Pubmed, EMbase, and relevant database articles (1996.01-2013.12). Comparative studies were carried out on proved fungal infections, mortality, and adverse effects. Meta-analysis was performed by Review Manager 5.1.6 software and the funnel plot regression was adopted to assess the publication bias. RESULTS: We found 1508 records and 13 studies totaling 3767 patients included in analyses. Pooled comparisons of studies found that antifungal prophylaxis with the new agents does reduce the incidence of invasive fungal infections than fluconazole or itraconazole. The reduction in invasive fungal infections was achieved by using micafungin, voriconazole for antifungal prophylaxis. Using voriconazole prophylaxis can decrease the transplant mortality compared with fluconazole or itraconazole prophylaxis. Voriconazole had higher rates of liver dysfunction, lower gastrointestinal side effects over fluconazole, and lower rates of nephrotoxic effects than amphotericin B. Both micafungin and voriconazole had a significant decrease in adverse events requiring drug discontinuation compared with itraconazole. CONCLUSIONS: This analysis indicated the 2 agents appear to be well tolerated with manageable side effects and beneficial in the prophylaxis of IFI. Further work is needed with a large scale of random controlled trials on the effect of these drugs. PMID- 26875912 TI - Computational model of the fathead minnow hypothalamic-pituitary-gonadal axis: Incorporating protein synthesis in improving predictability of responses to endocrine active chemicals. AB - There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic pituitary-gonadal (HPG) axis in female fathead minnows exposed to a model aromatase inhibitor, fadrozole (FAD), to predict dose-response and time-course behaviors for apical reproductive endpoints. Initial efforts to develop a computational model describing adaptive responses to endocrine stress providing good fits to empirical plasma 17beta-estradiol (E2) data in exposed fish were only partially successful, which suggests that additional regulatory biology processes need to be considered. In this study, we addressed short-comings of the previous model by incorporating additional details concerning CYP19A (aromatase) protein synthesis. Predictions based on the revised model were evaluated using plasma E2 concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two fathead minnow time-course experiments with FAD, as well as from a third 4-day study. The extended model provides better fits to measured E2 time course concentrations, and the model accurately predicts CYP19A mRNA fold changes and plasma E2 dose-response from the 4-d concentration-response study. This study suggests that aromatase protein synthesis is an important process in the biological system to model the effects of FAD exposure. PMID- 26875913 TI - Bioconcentration and endocrine disruption effects of diazepam in channel catfish, Ictalurus punctatus. AB - Recently, the detection of pharmaceuticals in surface waters has increased worldwide. Pharmaceuticals are typically found in the environment at concentrations well below therapeutic levels in humans; however, their mechanisms of action may be largely unknown in non-target organisms, such as teleost species. Thus, chronic exposure to these types of compounds warrants further investigation. The goal of this study was to examine the potential for diazepam, a model benzodiazepine drug, to bioconcentrate in tissues of channel catfish and to examine its ability to interact with the endocrine system through modulation of steroid hormones and/or steroidogenic genes. To investigate the bioconcentration potential of diazepam, channel catfish (Ictalurus punctatus) were exposed to 1 ng/mL diazepam for seven days, followed by clean water for another seven days, using an abbreviated OECD 305 Fish Bioconcentration Test study design. This concentration of diazepam is well below environmentally relevant concentrations of diazepam (ng/L). To evaluate steroidogenic effects, fish were exposed to 1 ng/mL diazepam for seven days only. Steroid hormone concentrations were analyzed for various tissues, as well as expression of selected steroidogenic genes. Calculated bioconcentration factors for diazepam were well below regulatory threshold values in all tissues analyzed. No changes in steroid hormone concentration were detected in any tissue analyzed; however, the steroidogenic gene cytochrome P450 side chain cleavage (P450scc) was significantly down-regulated at day 5 and 3beta-hydroxy steroid dehydrogenase (3beta-HSD) was significantly down-regulated at day 7 in the gonad. These results indicate that although diazepam does not significantly bioconcentrate, low-level chronic exposure to diazepam may have the potential to interact with endocrine function by altering gene expression. PMID- 26875914 TI - Gastroschisis in a fetus with a congenital neuroblastoma: Association or coincidence? AB - BACKGROUND: Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common malignant tumor observed during the neonatal period. It is a neuroendocrine tumor derived from neural crest cells that develops into the adrenal gland. CASE: We report on the undescribed association between gastrochisis and congenital neuroblastoma, diagnosised during the prenatal period. The mother was a 20-year-old healthy pregnant woman in her second pregnancy. Obstetric ultrasound examination showed a fetus presenting an abdominal wall defect on the right side of the umbilical cord, compatible with gastroschisis, and a hyperechogenic and spherical solid lesion on the left adrenal gland. Fetal magnetic resonance imaging disclosed similar features associated to a heterogeneous aspect of the liver. The diagnosis of metastatic neuroblastoma was confirmed after birth through liver biopsy. At 2 days of life, the prothrombrin time was abnormal, and the patient needed vitamin K. CONCLUSION: We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis occurring around 3 to 4 weeks of gestation, a period when neuroblasts development occurs into the adrenal medulla. However, we cannot exclude the possibility that both events may have occurred simultaneously by chance. PMID- 26875915 TI - [Precision medicine, opportunities and challenges for pancreatic cancer prevention and treatment]. PMID- 26875916 TI - [Multidisciplinary treatment and survival analysis for 497 cases of pancreatic cancer with liver metastases]. AB - OBJECTIVE: To explore the multidisciplinary therapeutic mode, clinical effect and prognostic factors of pancreatic cancer with liver metastases (PCLM). METHODS: We retrospectively selected 497 consecutive patients with PCLM who were pathologically diagnosed and treated at Tianjin Medical University Cancer Hospital, from January, 2000 to December, 2012. Clinical characteristics, treatment modality, survival condition and factors associated with prognosis of these cases were analyzed, and efficacy of multidisciplinary treatment model was evaluated. RESULTS: Of these patients, the male/female ratio was 1.85?1, with a median age of 59. A total of 358 (72.0%) cases had synchronous liver metastases, and 173 (34.8%) cases complicated with extrahepatic metastases. The 0.5, 1, 3, 5 year survival rates of 497 patients were 44.1%, 19.7%, 3.2% and 2.2%, respectively, with a median survival (MS) of 5.4 months. Patients who were treated with 3 or more approaches (including surgery, chemotherapy, radiation therapy, interventional therapy, and physiotherapy) had a longer median survival time than patients treated with 2 or only 1 approach (MS: 8.6 vs 5.2 vs 4.6 months, P< 0.001). Multivariate analysis for clinical features and treatment modality showed that age, weight loss, ascites, karnofsky performance score (KPS), primary site resection, albumin, carbohydrate antigen (CA) 19-9, resection of liver metastases, radiation therapy and systemic chemotherapy were prognostic variables with statistical significance. CONCLUSIONS: PCLM is a refractory malignant tumor. Age >60, weight loss (>=10% within 3 months), ascites, KPS <80, albumin<35 g/L, and CA19-9 >=500 U/ml were the most relevant predictors of poor survival. Multimodal treatment using curative resection of pancreatic cancer and/or liver metastases, systemic chemotherapy and radiation therapy may improve the prognosis and survival rate sufficiently. PMID- 26875917 TI - [Observation on the efficacy of modified Appleby operation for carcinoma of the body and tail of the pancreas]. AB - OBJECTIVE: To evaluate the security, feasibility and therapeutic efficacy of modified Appleby operation for carcinoma of the body and tail of pancreas. METHODS: From March 2010 to February 2015 modified Appleby operation was performed in 17 patients with carcinoma of the body and tail of the pancreas. The biochemical indices of fasting plasma blood (FPB), body weight (BW), visual analogue pain intensity scale (VAS score) and the quality of life index were evaluated before and 1 day , 1, 2, 6weeks after surgery. Survival time, tumor recurrence time, hospitalization time and treatment-related complications were analyzed. RESULTS: There was no hospital mortality in this study. Pancreatic fistula and diarrhea were the major complications. The overall complication rate was 47.1%. The liver function index of ALT and AST were increased on postoperative day 1, and they were restored to normal after one week. Blood glucose has no obvious abnormal increase and abdominal pain was completely relieved. The VAS score decreased after surgery comparing with before (1.9+/-3.6 vs 83.2+/-8.5, P<0.05). Life quality assessment was significantly higher. The body weight of patients after surgery has a mean increment of (4.1+/-1.3)kg than that before surgery (68.1+/-4.3 vs 64.0+/-6.7, P<0.05). A significant rise of the overall quality of life index was observed after surgery (93.8+/-9.7 vs 68.6+/ 6.7, P<0.05). The recurrence rates of 1, 2, 3 and 5 years were 22.9%, 58.9%, 72.6% and 72.6%, respectively. Median recurrence time was (20.0+/-3.8 m) (95%CI: 12.6-27.4 m). The survival rates of 1, 2, 3 and 5 years were 80.4%, 54.2%, 32.5% and 16.3%, respectively. The median survival time was (26.0+/-6.0)m (95%CI: 14.2 37.8 m). CONCLUSIONS: Modified Appleby operation for pancreatic cancer is safe and feasible. It can relieve abdominal pain, improve the quality of life, improve the survival rate and prolong the survival time. PMID- 26875918 TI - [Telescopic technique associated with mucosectomy in pancreaticoduodenectomy]. AB - OBJECTIVE: To explore the feasibility of the telescopic technique associated with mucosectomy in preventing pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: The data of 39 patients who received PD in the Affiliated Hospital of Nantong University was retrospecively analyzed. We developed a safe and simple method of pancreaticojejunostomy in 39 patients, in whom approximately 3 cm of jejunal mucosa was cut to improve the adhesion between the loop and pancreatic parenchyma after end-to-end invagination. RESULTS: This procedure was proved to be much more expeditious, and only 2 of 39(5.1%)patients had pancreatic leakages, who were treated with drainage only. No hemorrhage or cholangitis was observed. No postoperative mortality was observed. CONCLUSION: The telescopic technique associated with mucosectomy is an acceptable and safe surgery for pancreaticojejunal anastomosis. PMID- 26875919 TI - [Inhibition of Sirolimus on the growth of pancreatic carcinoma and its effect on the expression of glucose transporter and hexokinase II]. AB - OBJECTIVE: To investigate whether Sirolimus could affect the glycolytic catabolism pathways of pancreatic carcinoma through the control of hypoxia induced factor (HIF-1alpha) to inhibit the growth of tumor, and explore the potential mechanism of targeting the signaling pathways of mTOR for the treatment of pancreatic carcinoma. METHODS: Sirolimus was applied to treat the pancreatic carcinoma in nude mice orthotopic transplantation model, its difference with the control group was compared; RT-PCR and Western blot were used to measure the mRNA and protein expression of mTOR, HIF-1alpha, Glucose carrier protein 1 (GLUT-1) and Hexokinase II (HK-II), respectively; the changes of activity of HK-II in the tumor was determined. RESULTS: The tumor mass of the control group (1.97+/-0.21)g was significantly larger than that of the Sirolimus group (0.38+/-0.10)g (P<0.01), and the volume of the control group (1.40+/-0.15) mm(3) was significantly larger than that of the Sirolimus group (0.27+/-0.07) mm(3) (P<0.01). The expressions of mTOR, GLUT-1 and HK-II mRNA in the control group were higher than those of the Sirolimus group (P<0.05), while no significant change was observed in the expression of HIF-1alpha (P>0.05); the expressions of p-mTOR, HIF-1alpha, GLUT-1 and HK-II proteins in the control group were higher than those of the Sirolimus group (P<0.05). The activity of HK-II in the control group was higher than that of the Sirolimus group (P<0.05). CONCLUSION: Sirolimus could affect the expression of GLUT-1 and HK-II in pancreatic carcinoma through the effects of HIF-1alpha to inhibit tumor growth, indicating that blocking the mTOR pathway could control the glycolytic metabolism pathways of pancreatic carcinoma, which may become the new strategy for the treatment of pancreatic carcinoma. PMID- 26875920 TI - [Nutritional risk screening in patients with Crohn's disease]. AB - OBJECTIVE: To screen the nutritional risk in patients with Crohn's disease (CD), to explore the prevalence and characteristics of nutritional risk in CD patients, and to identify the possible risk factors. METHOD: A cross-sectional study was performed in 712 patients who was diagnosed as CD in the Center for Inflammatory Bowel Disease of First Affiliated Hospital of Sun Yat-sen University between January 2003 and January 2014. Montreal classification was used to classify CD, Crohn's Disease Activity Index (CDAI) was used to evaluate disease activity, and Nutritional Risk Screening 2002 (NRS2002) was used to assess the nutritional risk in each patient. Reappraisal with NRS 2002 was conducted in patients followed up for 1 year to identify the possible effect of treatment on nutritional risk of the CD patients. RESULTS: The prevalence of nutritional risk was 65.2% (464/712) in the enrolled CD patients. The prevalence of nutritional risk was significantly different among patients with different disease activity (chi(2)=117.169, P<0.001), also significantly different among patients of different age at diagnosis (chi(2)=11.256, P=0.004), with different lesion location (chi(2)=18.841, P=0.001) and different disease behavior (chi(2)=15.793, P<0.001), but not significantly different in patients of different sex (chi(2)=0.601, P=0.245). Multivariate Logistic regression showed that the independent predictive risk factors for nutritional risk included abdominal tenderness (OR=1.895, 95%CI: 1.080-3.324); mild (OR=1.846, 95%CI: 1.179-2.890), moderate (OR=4.410, 95%CI: 2.701-7.200) and severe (OR=14.069, 95%CI: 1.718-115.192) disease activity; B2 (stricturing) (OR=1.620, 95%CI: 1.034-2.538) and B3 (penetrating) (OR=1.920, 95%CI: 1.025-3.596) types of disease behavior; and high level with erythrocyte sedimentation rate (ESR) (OR=1.024, 95%CI: 1.015-1.034). On the other hand, >40 years at diagnosis (A3 type) (OR=0.332, 95%CI: 0.135-0.814) and high albumin level (OR=0.962, 95%CI: 0.934-0.990) were independent protective factors for nutritional risk. After 1-year follow-up, nutritional risk was eliminated in 32.0%(111/347)of the patients, and the rate was higher in patients received surgery than in those treated with medicine alone (42.9%(54/126)vs 25.8%(57/221), chi(2)=10.742, P=0.001). CONCLUSIONS: Two thirds of CD patients may have nutritional risk at diagnosis, which may differ with disease activity and Montreal classification. Abdominal tenderness, disease activity, B2 and B3 types of disease behavior, and high ESR may be independent risk factors for nutritional risk, whereas A3 type of age at diagnosis and high albumin level may be independent protective factors. PMID- 26875921 TI - [Efficacy and safety analysis of surgical bypass and endovascular management in the treatment of 116 Takayasu arteritis]. AB - OBJECTIVE: To analyze the efficacy and safety of surgery and endovascular management in treating Takayasu arteritis. METHODS: The data of 116 patients (24 males and 92 females; mean age (32+/-12) years) with Takayasu arteritis and underwent surgery or endovascular therapy was retrospective analyzed. According to the two different surgical procedures, the patients were divided into two groups: open repair group and endovascular repair group. One hundred and fifty four surgical procedures were done including 69 cases of open repair and 85 cases of endovascular repair. A total of 211 arterial lesions were revascularized (open repair 114; endovascular repair 97). RESULTS: Among the 154 surgical procedures, 11(7.1%) presented a complication during perioperative period including 6(8.7%) of open repair and 5(5.9%) of endovascular repair. After a median follow-up of 38.5(0.5-142.0) months, three(4.3%) cases of stroke and death were observed in open repair group, two(2.3%) cases of stroke and 4(4.7%) cases of death were observed in endovascular repair group. At 1, 3, 5 and 10 years of follow-up, primary patency rate of open repair and endovascular repair were 95.0% and 89.3%, 84.3% and 69.8%, 73.3% and 56.3%, 53.4% and 48.1%, respectively; Primary assisted patency rate were 100% and 97.5%, 90.4% and 78.2%, 79.1% and 72.8%, 60.7% and 54.0%, respectively; Secondary patency rate were 100% and 98.8%, 95.6% and 92.7%, 85.8% and 78.1%, 74.8% and 58.0%, respectively. Cumulative survival rate were 97.0% and 100%, 97.0% and 97.6%, 97.0% and 90.6%, 91.3% and 84.5%, respectively (chi(2)=0.182, P=0.669). CONCLUSIONS: Both of the surgical revascularization and endovascular management are safe and effective in the treatment of Takayasu arteritis. Although long-term patency of endovascular therapy is low, it can be performed repeatedly and can be used as a preferred approach in treating a short stenosis. Surgical repair shows excellent long-term durability, it seems to be more suitable for complex lesions and failure cases of endovascular management. PMID- 26875922 TI - [Comparison of jaw thrust and trapezius squeezing test as indicators for laryngeal mask airway insertion in infants and young children]. AB - OBJECTIVE: To compare the effectiveness of the jaw thrust and the trapezius squeezing test(TST) for laryngeal mask airway (LMA) insertion in infants and children under sevoflurane anesthesia. METHODS: A total of 100 children aged from 6 month to 3 years, American Society of Anesthesiologists(ASA) I-II and undergoing minor operation were enrolled from January to June 2015 in Tianjin Children's Hospital. The patients were randomly divided into jaw thrusting group (Group J, n=50)and trapezius squeezing group(Group T, n=50). Anesthesia was induced with sevoflurane. When children's eyelash reflex lose, jaw thrust/trapezius squeeze was applied every 15 seconds.It's considered that the depth of anesthesia was not enough, and test reaction was positive if any movements of body, limbs or toes were found at the point of test. Sevoflurane should be keep on inhalation until negative test reaction was appeared. Then LMA was inserted immediately.The time required for the negative test, end-tidal sevoflurane concentrations (ETsev), the index of Narcotrend anesthesia monitor(NT), the occurrence of gross purposeful movements, coughing, gagging, breath-holding, laryngospasm or an SpO2 < 90% during LMA insertion in two groups of patients were observed and recorded. The condition of LMA insertion and the rate of successful insertion were evaluated. The blood pressure(BP), heart rate(HR) and SpO2 were also recorded before and after LMA insertion. RESULTS: In group J and group T, the time required for the negative test was (2.31+/-1.03) vs (2.85+/-0.97)min(t=-2.462, P<0.05), ETsev was(3.25+/-1.02)% vs (3.81+/-0.87) %(t= 2.361, P<0.05), the depth of anesthesia NT index was(50.41+/-5.38) vs (41.32+/ 4.92)(t=3.021, all P<0.05). All of above results were significantly different. The successful rate of the first attempt LMA insertion was 78% vs 100%(chi(2)=12.36 , P<0.01), respectively. The differences had statistical significance. The conditions of LMA insertion in group T were superior to those in group J. The incidences of gross purposeful movements, coughing, gagging, breath-holding and SpO2<90% during LMA insertion in group J were 20%, 16%, 10%, 14% and 8%, which were higher than those in group T (2%, 2%, 0, 2%, 0), the differences were significant(chi(2)=8.27, 5.98, 5.26, 4.89, 4.17, all P<0.05). No significant change in blood pressure, heart rate and SpO2 were found before and after inserting LMA in two groups. CONCLUSION: The trapezius squeezing test is a superior indicator of adequate condition for LMA insertion compared to the jaw thrust in infants and young children under sevoflurane anesthesia. PMID- 26875923 TI - [Methylation status of PCDH10 and RASSF1A gene promoters in colorectal cancer]. AB - OBJECTIVE: To investigate the methylation status of promoters of protocadherin-10 (PCDH10) and Ras-association domain family 1A (RASSF1A) genes in colorectal cancer (CRC), and to study its relationship with development and progress of CRC. METHODS: Tumor tissues were collected from 75 CRC patients who received surgical treatment in the Affiliated Hospital of Guizhou Medical University in the period from 2007 to 2010. Methylation-specific polymerase chain reaction (MSP) was applied to detect the methylation status of PCDH10 and RASSF1A gene promoters in CRC and adjacent normal colorectal mucosa. The relationship between methylation of PCDH10 and RASSF1A and clinicopathological features of CRC was analyzed using chi-squared test. RESULTS: The rate of PCDH10 methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (58.7%(44/75)vs 22.7%(17/75), P<0.01). There was no significantly correlation between methylation of PCDH10 and patients' age, gender, tumor site, Dukes stage, and lymph node metastasis(all P>0.05). The rate of RASSF1A methylation in CRC tissue was significantly higher than that in colorectal normal mucosa (64.6%(42/65)vs 15.4%(10/65), P<0.01). There was no significantly correlation between methylation of RASSF1A and patients' age, gender, and tumor site (all P>0.05), but the patients in high Dukes stages and with lymph node metastasis had higher RASSF1A methylation rate(92.9%(26/28)vs 43.2%(16/37), 92.9%(26/28)vs 43.2%(16/37), both P<0.05). CONCLUSIONS: CRC tissues demonstrate high level of methylation of PCDH10 and RASSF1A genes, which may play a crucial role in the pathogenesis of CRC. The aberrant hypermethylation of RASSF1A gene is observed in more advanced CRC, suggesting that the RASSF1A gene methylation may be related to progression of CRC. PMID- 26875924 TI - [Survival and prognostic evaluation of superficial esophageal cancer after surgery]. AB - OBJECTIVE: To calculate the survival rate of patients with superficial esophageal squamous carcinoma who received esophageal resection and to explore factors that affect prognosis. METHODS: There were 285 patients with pTis-T1 esophageal carcinoma who underwent esophagectomy during 2007-2011. Their cumulative survival rates were calculated using life tables. Nine factors that may have impact on postoperative survival of superficial esophageal carcinoma were selected. The Kaplan-Meier method and COX's regression model were used to select prognostic factors, estimate prognostic index, and establish risk stratification. RESULTS: The 1-, 3- and 5-year overall survival rates of superficial esophageal carcinoma patients were 97%, 86%, and 82%, respectively. Tumor length, stenosis, depth of invasion, differentiation degree, lymph node metastasis, and vascular tumor thrombus were associated with prognosis according to univariate analysis. Depth of invasion (OR=2.065, P=0.029), lymph node metastasis (OR=2.049, P=0.041), differentiation degree (OR=3.828, P=0.000), stenosis(OR=2.129, P=0.048), and vascular tumor thrombus (OR=4.222, P=0.004) were independent prognostic factors in multivariate analysis. A prognostic models was thus established and all the patients were divided into low-risk, moderate-risk and high-risk group, with the 3-year survival rates being 95%, 84%, and 51%, and 5-year survival rates being 93%, 79%, and 44%, respectively. CONCLUSIONS: Patients with superficial esophageal cancer have relatively favorable prognosis. Depth of invasion, differentiation degree, stenosis, lymph node metastasis, and vascular tumor thrombus may be independent factors of poor prognosis. Survival rate of moderate- and high-risk patients is yet to be improved. PMID- 26875925 TI - [Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats]. AB - OBJECTIVE: To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. METHODS: Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. RESULTS: Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all P<0.01), and content of NO in the compound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29+/-0.51) vs(10.80+/-0.36)nmol/ml, P<0.05). The gastric mucosal lesion index, contents of TNF, and IL-1, 2, 8 were significantly lower in all the protection groups than in the injury group (all P<0.01), and contents of IL-2 and IL-8 in the compound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17+/-6.56) vs(340.23+/-8.05)pg/ml, P<0.01; (170.82+/-7.31) vs(179.31+/-7.80)pg/ml, P<0.05). Tissue injury and inflammatory reaction in all the protection groups were obviously mitigated compared with the injury group. CONCLUSION: Compound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury. PMID- 26875926 TI - [Expression and mechanism of nitric oxide synthase in cerebral hyperperfusion rats]. AB - OBJECTIVE: To explore the expression and mechanism of different nitric oxide synthase in cerebral hyperperfusion rats. METHODS: Male Wistar rats were anesthetized and a ventral midline incision was made. The bilateral common carotid arteries were gently separated. Each artery was ligated with a 5-0 silk suture. Sham groups underwent the same operation without occlusion two weeks later, the ligature was loosened under a microscope to induce reperfusion. Phenylephrine was administered at concentration of 50 MUg/ml via tail vein.After hyperperfusion, the expression of iNOS and eNOS in hippocampus , cortex and common carotid arteries of rats brain was observed by using Western blot of each group. RESULTS: The expression of iNOS in differernt sites were increased significantly after reperfusion of 24 hours. The ratio of iNOS and beta-actin in hippocampus in sham, BCAO, HP, HP 24 and HP 48 groups were 21.10+/-2.53, 24.37+/ 2.30, 28.34+/-2.86, 43.76+/-2.58, 38.90+/-3.17, respectively. There was significant difference between HP 24 and other groups (F=13.03, all P<0.05). The ratio of iNOS and beta-actin in cortex in each group were 12.98+/-2.31, 15.00+/ 1.66, 14.71+/-1.48, 34.76+/-5.01, 32.60+/-5.73, respectively (F=8.42, all P<0.05). The ratio of iNOS and beta-actin in common carotid arteries in each group were 7.30+/-2.55, 8.83+/-1.45, 4.76+/-0.71, 28.00+/-2.21, 26.29+/-3.33 (F=24.82, all P<0.05). While the levels of eNOS in that three sites presented no significant change(all P>0.05). CONCLUSIONS: Hyperperfusion can induce iNOS ecpression in quantities in hippocamps, cortex and common carotid arteries. These levesl would last until 48 hours after reperfusion. This process suggests that iNOS is the possible mechanism of hyperperfusion. PMID- 26875928 TI - Corrigenda. PMID- 26875927 TI - Age- and performance-related differences in hippocampal contributions to episodic retrieval. AB - The goal of the present study was to investigate whether hippocampal contribution to episodic memory retrieval varies as a function of age (8-9 versus 10-11 versus adults), performance levels (high versus low) and hippocampal sub-region (head, body, tail). We examined fMRI data collected during episodic retrieval from a large sample (N=126). Participants judged whether a stimulus had been encoded previously, and, if so, which of three scenes it had been paired with (i.e., source judgment). For 8- to 9-years-olds as well as low-performing 10- to 11-year olds, hippocampal activations did not reliably differentiate between trials on which item-scene associations were correctly recalled (correct source), incorrectly recalled (incorrect source), or trials on which the item was forgotten (miss trials). For high-performing 10-11-year olds and low-performing adults, selective hippocampal activation was observed for correct source relative to incorrect source and miss trials; this effect was observed across the entire hippocampus. For high-performing adults, hippocampal activation also distinguished between correct and incorrect source trialsl, but only in the hippocampal head, suggesting that good performance in adults is associated with more focal hippocampal recruitment. Thus, both age and performance are important factors for understanding the development of memory and hippocampal function. PMID- 26875929 TI - Thermally stable dielectric responses in uniaxially (001)-oriented CaBi4Ti4O15 nanofilms grown on a Ca2Nb3O10- nanosheet seed layer. AB - To realize a high-temperature capacitor, uniaxially (001)-oriented CaBi4Ti4O15 films with various film thicknesses were prepared on (100)cSrRuO3/Ca2Nb3O10(-) nanosheet/glass substrates. As the film thickness decreases to 50 nm, the out-of plane lattice parameters decrease while the in-plane lattice ones increase due to the in-plane tensile strain. However, the relative dielectric constant (epsilonr) at room temperature exhibits a negligible degradation as the film thickness decreases to 50 nm, suggesting that epsilonr of (001)-oriented CaBi4Ti4O15 is less sensitive to the residual strain. The capacitance density increases monotonously with decreasing film thickness, reaching a value of 4.5 MUF/cm(2) for a 50-nm-thick nanofilm, and is stable against temperature changes from room temperature to 400 degrees C irrespective of film thickness. This behaviour differs from that of the widely investigated perovskite-structured dielectrics. These results show that (001)-oriented CaBi4Ti4O15 films derived using Ca2Nb3O10( ) nanosheets as seed layers can be made candidates for high-temperature capacitor applications by a small change in the dielectric properties against film thickness and temperature variations. PMID- 26875930 TI - HOSPITAL MANAGERS' NEED FOR INFORMATION ON HEALTH TECHNOLOGY INVESTMENTS. AB - OBJECTIVES: There is growing interest in implementing hospital-based health technology assessment (HB-HTA) as a tool to facilitate decision making based on a systematic and multidisciplinary assessment of evidence. However, the decision making process, including the informational needs of hospital decision makers, is not well described. The objective was to review empirical studies analysing the information that hospital decision makers need when deciding about health technology (HT) investments. METHODS: A systematic review of empirical studies published in English or Danish from 2000 to 2012 was carried out. The literature was assessed by two reviewers working independently. The identified informational needs were assessed with regard to their agreement with the nine domains of EUnetHTA's Core Model. RESULTS: A total of 2,689 articles were identified and assessed. The review process resulted in 14 relevant studies containing 74 types of information that hospital decision makers found relevant. In addition to information covered by the Core Model, other types of information dealing with political and strategic aspects were identified. The most frequently mentioned types of information in the literature related to clinical, economic and political/strategic aspects. Legal, social, and ethical aspects were seldom considered most important. CONCLUSIONS: Hospital decision makers are able to describe their information needs when deciding on HT investments. The different types of information were not of equal importance to hospital decision makers, however, and full agreement between EUnetHTA's Core Model and the hospital decision-makers' informational needs was not observed. They also need information on political and strategic aspects not covered by the Core Model. PMID- 26875932 TI - Effective medical treatment strategies to help cessation of purging behaviors. AB - OBJECTIVE: Herein we review the major medical issues involved in the "detoxing" of patients who engage in purging behaviors and the pathophysiology of why they occur. METHODS: Given a limited evidence base of randomized controlled trials, we conducted a thorough qualitative review to identify salient literature with regard to the medical issues involved in "detoxing" patients from their purging behaviors. RESULTS: Pseudo Bartter's Syndrome is the root cause of much of the medical difficulties which can arise when purging behaviors are abruptly discontinued. However, this is imminently treatable and even preventable with a judicious medical treatment plan which targets the increased serum aldosterone levels which would otherwise promote salt and water retention and a propensity towards severe edema formation. Effective recommendations are provided which can make this process much less vexing for patients attempting to cease their purging behaviors. CONCLUSIONS: "Detoxing" from purging behaviors can be fraught with medical complications which frustrate these patients and can lead to unsuccessful outcomes. Medical providers should become familiar with the pathophysiology which is the basis for Pseudo Bartter's Syndrome and the effective medical treatments which can lead to a successful outcome. PMID- 26875931 TI - Sensory rooms in psychiatric inpatient care: Staff experiences. AB - There is an increased interest in exploring the use of sensory rooms in psychiatric inpatient care. Sensory rooms can provide stimulation via sight, smell, hearing, touch and taste in a demand-free environment that is controlled by the patient. The rooms may reduce patients' distress and agitation, as well as rates of seclusion and restraint. Successful implementation of sensory rooms is influenced by the attitudes and approach of staff. This paper presents a study of the experiences of 126 staff members who worked with sensory rooms in a Swedish inpatient psychiatry setting. A cross-sectional descriptive survey design was used. Data were collected by a web based self-report 12-item questionnaire that included both open- and closed-ended questions. Our findings strengthen the results of previous research in this area in many ways. Content analyses revealed three main categories: hopes and concerns, focusing on patients' self-care, and the room as a sanctuary. Although staff initially described both negative and positive expectations of sensory rooms, after working with the rooms, there was a strong emphasis on more positive experiences, such as letting go of control and observing an increase in patients' self-confidence, emotional self-care and well being. Our findings support the important principals of person-centred nursing and recovery-oriented mental health and the ability of staff to implement these principles by working with sensory rooms. PMID- 26875933 TI - Development of 3-(4-aminosulphonyl)-phenyl-2-mercapto-3H-quinazolin-4-ones as inhibitors of carbonic anhydrase isoforms involved in tumorigenesis and glaucoma. AB - A series of heterocyclic benzenesulfonamides incorporating 2-mercapto-3H quinazolin-4-one tails were prepared by condensation of substituted anthranilic acids with 4-isothiocyanato-benzenesulfonamide. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA IX and XII (trans membrane, tumor-associated enzymes). They acted as medium potency inhibitors of hCA I (KIs of 81.0-3084 nM), being highly effective as hCA II (KIs in the range of 0.25-10.8 nM), IX (KIs of 3.7-50.4 nM) and XII (KIs of 0.60-52.9 nM) inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of three isoforms (CA II, IX and XII) is dysregulated. PMID- 26875934 TI - Synthesis and pharmacological evaluation of nucleoside prodrugs designed to target siderophore biosynthesis in Mycobacterium tuberculosis. AB - The nucleoside antibiotic, 5'-O-[N-(salicyl)sulfamoyl]adenosine (1), possesses potent whole-cell activity against Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB). This compound is also active in vivo, but suffers from poor drug disposition properties that result in poor bioavailability and rapid clearance. The synthesis and evaluation of a systematic series of lipophilic ester prodrugs containing linear and alpha-branched alkanoyl groups from two to twelve carbons at the 3'-position of a 2'-fluorinated analog of 1 is reported with the goal to improve oral bioavailability. The prodrugs were stable in simulated gastric fluid (pH 1.2) and under physiological conditions (pH 7.4). The prodrugs were also remarkably stable in mouse, rat, and human serum (relative serum stability: human~rat?mouse) displaying a parabolic trend in the SAR with hydrolysis rates increasing with chain length up to eight carbons (t1/2=1.6 h for octanoyl prodrug 7 in mouse serum) and then decreasing again with higher chain lengths. The permeability of the prodrugs was also assessed in a Caco-2 cell transwell model. All of the prodrugs were found to have reduced permeation in the apical-to-basolateral direction and enhanced permeation in the basolateral-to apical direction relative to the parent compound 2, resulting in efflux ratios 5 28 times greater than 2. Additionally, Caco-2 cells were found to hydrolyze the prodrugs with SAR mirroring the serum stability results and a preference for hydrolysis on the apical side. Taken together, these results suggest that the described prodrug strategy will lead to lower than expected oral bioavailability of 2 and highlight the contribution of intestinal esterases for prodrug hydrolysis. PMID- 26875935 TI - Discovery of human Golgi beta-galactosidase with no identified glycosidase using a QMC substrate design platform for exo-glycosidase. AB - Post-translational modifications (PTMs) of proteins play important roles in the physiology of eukaryotes. In the PTMs, non-reversible glycosylations are classified as N-glycosylations and O-glycosylations, and are catalyzed by various glycosidases and glycosyltransferases. However, beta-glycosidases are not known to play a role in N- and O-glycan processing, although both glycans provide partial structures as substrates for beta-galactosidase and beta-N acetylglucosaminidase in the Golgi apparatus of human cells. We explored human Golgi beta-galactosidase using fluorescent substrates based on a quinone methide cleavage (QMC) substrate design platform that was previously developed to image exo-type glycosidases in living cells. As a result, we discovered a novel Golgi beta-galactosidase in human cells. It is possible to predict a novel and important function in glycan processing of this beta-galactosidase, because various beta-galactosyl linkages in N- and O-glycans exist in Golgi apparatus. In addition, these results show that the QMC platform is excellent for imaging exo type glycosidases. PMID- 26875936 TI - (99m)Tc-bioorthogonal click chemistry reagent for in vivo pretargeted imaging. AB - Metal-free click chemistry has become an important tool for pretargeted approaches in the molecular imaging field. The application of bioorthogonal click chemistry between a pretargeted trans-cyclooctene (TCO) derivatized monoclonal antibody (mAb) and a (99m)Tc-modified 1,2,4,5-tetrazine for tumor imaging was examined in vitro and in vivo. The HYNIC tetrazine compound was synthesized and structurally characterized, confirming its identity. Radiolabeling studies demonstrated that the HYNIC tetrazine was labeled with (99m)Tc at an efficiency of >95% and was radiochemically stable. (99m)Tc-HYNIC tetrazine reacted with the TCO-CC49 mAb in vitro demonstrating its selective reactivity. In vivo biodistribution studies revealed non-specific liver and GI uptake due to the hydrophobic property of the compound, however pretargeted SPECT imaging studies demonstrated tumor visualization confirming the success of the cycloaddition reaction in vivo. These results demonstrated the potential of (99m)Tc-HYNIC tetrazine for tumor imaging with pretargeted mAbs. PMID- 26875938 TI - Dendronized Anionic Gold Nanoparticles: Synthesis, Characterization, and Antiviral Activity. AB - Anionic carbosilane dendrons decorated with sulfonate functions and one thiol moiety at the focal point have been used to synthesize water-soluble gold nanoparticles (AuNPs) through the direct reaction of dendrons, gold precursor, and reducing agent in water, and also through a place-exchange reaction. These nanoparticles have been characterized by NMR spectroscopy, TEM, thermogravimetric analysis, X-ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, elemental analysis, and zeta-potential measurements. The interacting ability of the anionic sulfonate functions was investigated by EPR spectroscopy with copper(II) as a probe. Different structures and conformations of the AuNPs modulate the availability of sulfonate and thiol groups for complexation by copper(II). Toxicity assays of AuNPs showed that those produced through direct reaction were less toxic than those obtained by ligand exchange. Inhibition of HIV-1 infection was higher in the case of dendronized AuNPs than in dendrons. PMID- 26875939 TI - Solid-State NMR and DFT Studies on the Formation of Well-Defined Silica-Supported Tantallaaziridines: From Synthesis to Catalytic Application. AB - Single-site, well-defined, silica-supported tantallaaziridine intermediates [=Si O-Ta(eta(2) -NRCH2 )(NMe2 )2 ] [R=Me (2), Ph (3)] were prepared from silica supported tetrakis(dimethylamido)tantalum [=Si-O-Ta(NMe2 )4 ] (1) and fully characterized by FTIR spectroscopy, elemental analysis, and (1) H,(13) C HETCOR and DQ TQ solid-state (SS) NMR spectroscopy. The formation mechanism, by beta-H abstraction, was investigated by SS NMR spectroscopy and supported by DFT calculations. The C-H activation of the dimethylamide ligand is favored for R=Ph. The results from catalytic testing in the hydroaminoalkylation of alkenes were consistent with the N-alkyl aryl amine substrates being more efficient than N dialkyl amines. PMID- 26875940 TI - Breaking and Making of Carbon-Carbon Bonds by Lanthanides and Third-Row Transition Metals. AB - Carbon-atom extrusion from the ipso-position of a halobenzene ring (C6 H5 X; X=F, Cl, Br, I) and its coupling with a methylene ligand to produce acetylene is not confined to [LaCH2 ](+) ; also, the third-row transition-metal complexes [MCH2 ](+) , M=Hf, Ta, W, Re, and Os, bring about this unusual transformation. However, substrates with substituents X=CN, NO2 , OCH3 , and CF3 are either not reactive at all or give rise to different products when reacted with [LaCH2 ](+) . In the thermal gas-phase processes of atomic Ln(+) with C7 H7 Cl substrates, only those lanthanides with a promotion energy small enough to attain a 4f(n) 5d(1) 6s(1) configuration are reactive and form both [LnCl](+) and [LnC5 H5 Cl](+) . Branching ratios and the reaction efficiencies of the various processes seem to correlate with molecular properties, like the bond-dissociation energies of the C X or M(+) -X bonds or the promotion energies of lanthanides. PMID- 26875942 TI - Could procoagulant cell-derived microparticles have a more crucial role in pregnancy complications rather than exosomes? PMID- 26875941 TI - Overuse of external beam radiotherapy for stage I endometrial cancer. AB - BACKGROUND: Radiation therapy has long been part of the treatment of endometrial cancer. Despite the long history of radiation use, prospective trials in the United States and Europe have been unable to demonstrate a survival benefit with adjuvant radiotherapy compared with observation. Whereas radiation has been associated with a decreased rate of locoregional failure, the treatment is also associated with substantial toxicity. However, a randomized trial published in 2010 demonstrated that, compared with external beam radiation therapy (EBRT), vaginal brachytherapy was less toxic and as effective in reducing locoregional relapses. OBJECTIVE: We examined patterns of use of external beam radiation therapy for women with high intermediate risk endometrial cancer. STUDY DESIGN: We examined the use of external beam radiation therapy in women registered in the National Cancer Data Base with high intermediate risk, stage I endometrial cancer treated from 2008 through 2012. High intermediate risk was defined as age > 60 years with a stage IA, grade 3 tumors or stage IB, grade 1 or 2 tumors. Multivariable models of EBRT use were developed. RESULTS: Among 8242 women, 915 (11.1%) received EBRT, 2614 (31.7%) were treated with brachytherapy, and 4713 (57.2%) did not receive any adjuvant radiation. The use of EBRT was 18.1% in 2008 and declined to 8.6% in 2012, whereas the use of brachytherapy rose each year from 26.5% in 2008 to 37.6% in 2012 (P < .0001). External beam radiation was administered to 7.9% of patients with stage IA/grade 3 tumors, 8.8% of those with stage IB/grade 1 cancers, and to 15.2% of women with stage IB/grade 2 neoplasms (P < .0001). EBRT was utilized in 10.1% of women who underwent lymphadenectomy compared with 22.0% who did not undergo lymphadenectomy (P < .0001). In a multivariable model, black women were more likely to receive EBRT than white women (relative risk [RR], 1.33; 95% confidence interval [CI], 1.03-1.70). Similarly, patients in the eastern United States, those treated at community cancer centers and comprehensive community cancer programs, patients in metropolitan areas, and those diagnosed in earlier years were more likely to undergo EBRT. Patients with stage IB/grade 2 tumors (RR, 1.96; 95% CI, 1.65-2.32) were more likely to receive EBRT than those with stage IA/grade 3 neoplasms. Those women who did not undergo lymphadenectomy were more than twice as likely to receive EBRT compared with those who had a lymphadenectomy (RR, 2.32; 95% CI, 1.99-2.72). CONCLUSION: Despite data from randomized trials, approximately 9% of women with high intermediate risk of endometrial cancer continue to receive EBRT. Performance of lymphadenectomy is associated with a lower likelihood of external beam radiation therapy. PMID- 26875943 TI - Diagnosis and management of vasa previa. PMID- 26875944 TI - The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia. AB - BACKGROUND: Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. OBJECTIVE: We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. STUDY DESIGN: We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecology and Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes. Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the chi(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normally or not normally distributed. RESULTS: Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P = .03), but there was no difference in recurrence (13% vs 11%, P = .89). Patients with high risk gestational trophoblastic neoplasia lived 63 miles farther (92 vs 28 miles, P < .001) than patients with low-risk gestational trophoblastic neoplasia. Long distance travelers had a longer period between antecedent pregnancy and gestational trophoblastic neoplasia diagnosis (10 weeks vs 4.5 weeks, P = .009) and were more likely to receive multiagent chemotherapy (86% vs 61%, P = .03). CONCLUSION: In this cohort, long distance traveled to obtain care for gestational trophoblastic neoplasia was associated with an increased risk of presenting with high-risk disease and requiring multiagent chemotherapy for treatment. Patients with high-risk gestational trophoblastic neoplasia traveled nearly 100 miles to obtain care. There may be a delay in diagnosis in women traveling more than 50 miles to obtain care; however, we found no difference in recurrence risk for long distance travelers. PMID- 26875945 TI - Reply. PMID- 26875946 TI - Underuse of BRCA testing in patients with breast and ovarian cancer. PMID- 26875947 TI - Cell-free DNA fetal fraction and preterm birth. AB - BACKGROUND: Cell-free deoxyribonucleic acid (DNA) is increasingly being used to screen for fetal aneuploidy. The majority of fetal cell-free DNA in the maternal blood results from release from the syncytiotrophoblast as a result of cellular apoptosis and necrosis. Elevated levels of fetal cell-free DNA may be indicative of underlying placental dysfunction, which has been associated with preterm birth. Preliminary studies have demonstrated that fetal cell-free DNA is increased in pregnancies complicated by spontaneous preterm birth. There are limited data on the association between fetal cell-free DNA levels and fetal fraction and preterm birth in asymptomatic women in the first and second trimesters. Preliminary studies have failed to find an association between first trimester cell-free DNA levels and preterm birth, whereas there is conflicting evidence as to whether elevated second-trimester cell-free DNA is associated with a subsequent spontaneous preterm birth clinical event. OBJECTIVE: The objective of the study was to evaluate the association between first- and second-trimester cell-free DNA fetal fraction and preterm birth. STUDY DESIGN: This was a retrospective cohort study of women with singleton pregnancies at increased risk for aneuploidy who had cell-free DNA testing at 10-20 weeks' gestation between October 2011 and May 2014. The cohort was subdivided by gestational age at the time of cell-free DNA testing (10-14 weeks or 14.1-20 weeks). The primary outcome was preterm birth less than 37 weeks' gestation, and the secondary outcomes were preterm birth at less than 34 weeks' gestation and spontaneous preterm birth at less than 37 and 34 weeks' gestation. RESULTS: Among 1349 pregnancies meeting inclusion criteria 119 (8.8 %) had a preterm birth prior to 37 weeks with 49 cases (3.6 %) delivering prior to 34 weeks. Whereas there was no significant association between fetal fraction and the preterm birth outcomes for those who underwent cell-free DNA testing at 10-14 weeks' gestation, there were significant associations among those screened at 14.1-20.0 weeks' gestation. Fetal fraction greater than or equal to the 95th percentile at 14.1-20.0 weeks' gestation was associated with an increased risk for preterm birth less than 37 and 34 weeks' gestation (adjusted odds ratio, 4.59; 95% confidence interval, 1.39-15.2; adjusted odds ratio, 22.0; 95% confidence interval, 5.02-96.9). CONCLUSION: Elevated fetal fraction levels at 14.1-20.0 weeks' gestation were significantly associated with an increased incidence of preterm birth. Our findings warrant future exploration including validation in a larger, general population and investigation of the potential mechanisms that may be responsible for the initiation of preterm labor associated with increased fetal cell-free DNA. PMID- 26875948 TI - Accuracy of self-reported survey data on assisted reproductive technology treatment parameters and reproductive history. AB - BACKGROUND: It is unknown whether data obtained from maternal self-report for assisted reproductive technology treatment parameters and reproductive history are accurate for use in research studies. OBJECTIVES: We evaluated the accuracy of self-reported in assisted reproductive technology treatment and reproductive history from the Upstate KIDS study in comparison with clinical data reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. STUDY DESIGN: Upstate KIDS maternal questionnaire data from deliveries between 2008 and 2010 were linked to data reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System. The 617 index deliveries were compared as to treatment type (frozen embryo transfer and donor egg or sperm) and use of intracytoplasmic sperm injection and assisted hatching. Use of injectable medications, self-report for assisted reproductive technology, or frozen embryo transfer prior to the index deliveries were also compared. We report agreement in which both sources had yes or both no and sensitivity of maternal report using Society for Assisted Reproductive Technology Clinic Outcome Reporting System as the gold standard. Significance was determined using chi(2) at P < 0.05. RESULTS: Universal agreement was not reached on any parameter but was best for treatment type of frozen embryo transfer (agreement, 96%; sensitivity, 93%) and use of donor eggs (agreement, 97%; sensitivity, 82%) or sperm (agreement, 98%; sensitivity, 82%). Use of intracytoplasmic sperm injection (agreement, 78%: sensitivity, 78%) and assisted hatching (agreement, 57%; sensitivity, 38%) agreed less well with self-reported use (P < .0001). In vitro fertilization (agreement, 82%) and frozen embryo transfer (agreement, 90%) prior to the index delivery were more consistently reported than was use of injectable medication (agreement, 76%) (P < .0001). CONCLUSION: Women accurately report in vitro fertilization treatment but are less accurate about procedures handled in the laboratory (intracytoplasmic sperm injection or assisted hatching). Clinics might better communicate with patients on the use of these procedures, and researchers should use caution when using self-reported treatment data. PMID- 26875949 TI - Assessing ureteral patency using 10% dextrose cystoscopy fluid: evaluation of urinary tract infection rates. AB - BACKGROUND: Intravenous indigo carmine has routinely been used to confirm ureteral patency after urogynecologic surgery. Recent discontinuation of the dye has altered clinical practice. In the absence of indigo carmine, we have used 10% dextrose in sterile water (D10) as cystoscopic fluid to evaluate ureteral patency. Glucosuria has been associated with urinary tract infection (UTI) in vivo and significantly enhanced bacterial growth in vitro. The concern is that the use of D10 would mimic a state of glucosuria albeit transient and increase the risk of postoperative UTI. OBJECTIVES: The objectives of this study were to compare the rates of postoperative UTI and lower urinary tract (LUT) injuries between patients who underwent instillation of D10 vs normal saline at the time of intraoperative cystoscopy after urogynecological surgery. STUDY DESIGN: This was a retrospective cohort study of all women who underwent cystoscopic evaluation of ureteral patency at the time of urogynecological surgery from May through December 2014 at a tertiary care referral center. We compared patients who received D10 cystoscopy fluid vs those who used normal saline. Outcomes included UTI and diagnosis of ureteral or LUT injuries. UTI was diagnosed according to Centers for Disease Control and Prevention guidelines by symptoms alone, urine dipstick, urinalysis, or urine culture. Descriptive statistics compared the rates of UTI between the 2 groups, and a multivariable model was fit to the data to control for potential confounders and significant baseline differences between the groups. RESULTS: A total of 303 women were included. D10 was used in 113 cases and normal saline (NS) was used in 190. The rate of UTI was higher in the D10 group than the NS group: 47.8% (95% confidence interval [CI], 38.3-57.4) vs 25.9% (95% CI, 19.8-32.8, P < .001). After adjusting for age, pelvic organ prolapse stage, use of perioperative estrogen, days of postoperative catheterization, menopausal status, diabetes mellitus, and history of recurrent UTI, the UTI rate remained significantly higher with the use of D10 (adjusted odds ratio, 3.4 [95% CI, 1.6-7.5], P = .002) compared with NS. Overall, 3 cases of transient ureteral kinking (1.0%) and one cystotomy (0.3%) were identified intraoperatively. However, ureteral and LUT injuries were not different between groups. No unidentified injuries presented postoperatively. CONCLUSION: Although the use of D10 cystoscopy fluid has been successful in identifying ureteral patency in the absence of indigo carmine, it is associated with an increased rate of postoperative UTI compared with NS. PMID- 26875951 TI - Reply. PMID- 26875950 TI - Eliminating health disparities in unintended pregnancy with long-acting reversible contraception (LARC). AB - Significant public health disparities exist surrounding teen and unplanned pregnancy in the United States. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed, they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act and more widespread, no-cost coverage of methods, more and more women are choosing intrauterine devices and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the United States and improve women's and children's health. PMID- 26875952 TI - Pregnancy-induced adaptations in intramuscular extracellular matrix of rat pelvic floor muscles. AB - BACKGROUND: Birth trauma to pelvic floor muscles is a major risk factor for pelvic floor disorders. Intramuscular extracellular matrix determines muscle stiffness, supports contractile component, and shields myofibers from mechanical strain. OBJECTIVE: Our goal was to determine whether pregnancy alters extracellular matrix mechanical and biochemical properties in a rat model, which may provide insights into the pathogenesis of pelvic floor muscle birth injury. To examine whether pregnancy effects were unique to pelvic floor muscles, we also studied a hind limb muscle. STUDY DESIGN: Passive mechanical properties of coccygeus, iliocaudalis, pubocaudalis, and tibialis anterior were compared among 3-month old Sprague-Dawley virgin, late-pregnant, and postpartum rats. Muscle tangent stiffness was calculated as the slope of the stress-sarcomere length curve between 2.5 and 4.0 MUm, obtained from a stress-relaxation protocol at a bundle level. Elastin and collagen isoform concentrations were quantified by the use of enzyme-linked immunosorbent assay. Enzymatic and glycosylated collagen crosslinks were determined by high-performance liquid chromatography. Data were compared by the use of repeated-measures, 2-way analysis of variance with Tukey post-hoc testing. Correlations between mechanical and biochemical parameters were assessed by linear regressions. Significance was set to P < .05. Results are reported as mean +/- SEM. RESULTS: Pregnancy significantly increased stiffness in coccygeus (P < .05) and pubocaudalis (P < .0001) relative to virgin controls, with no change in iliocaudalis. Postpartum, pelvic floor muscle stiffness did not differ from virgins (P > .3). A substantial increase in collagen V in coccygeus and pubocaudalis was observed in late-pregnant, compared with virgin, animals, (P < .001). Enzymatic crosslinks decreased in coccygeus (P < .0001) and pubocaudalis (P < .02) in pregnancy, whereas glycosylated crosslinks were significantly elevated in late-pregnant rats in all pelvic floor muscles (P < .05). Correlations between muscle stiffness and biochemical parameters were inconsistent. In contrast to the changes observed in pelvic floor muscles, the tibialis anterior was unaltered by pregnancy. CONCLUSIONS: In contrast to other pelvic tissues, pelvic floor muscle stiffness increased in pregnancy, returning to prepregnancy state postpartum. This adaptation may shield myofibers from excessive mechanical strain during parturition. Biochemical alterations in pelvic floor muscle extracellular matrix due to pregnancy include increase in collagen V and a differential response in enzymatic vs glycosylated collagen crosslinks. The relationships between pelvic floor muscle biochemical and mechanical parameters remain unclear. PMID- 26875953 TI - Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30-34 weeks' gestation. AB - BACKGROUND: Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. We have proposed a 2 stage strategy for the identification of pregnancies at high risk of developing PE. The objective of the first stage, at 11-13 weeks' gestation, is a reduction in the prevalence of the disease through pharmacological intervention in the high risk group. The objective of the second stage, during the second and/or third trimesters, is to improve perinatal outcome through close monitoring of the high risk group for earlier diagnosis of the clinical signs of the disease and selection of the appropriate, time, place, and method of delivery. OBJECTIVE: The objective of the study was to examine the performance of screening for PE by a combination of maternal factors with early third-trimester biomarkers. STUDY DESIGN: This was a cohort study and data were derived from consecutive women with singleton pregnancies attending for their routine hospital visit at 30-34 weeks' gestation in 3 maternity hospitals in England between March 2011 and December 2014. In the first phase of the study, only uterine artery pulsatility index (UTPI) was measured and then measurement of mean arterial pressure (MAP) was added, and in the final phase, the serum concentration of placental growth factor (PLGF) was measured and then soluble fms-like tyrosine kinase-1 (SFLT) was added. We had data on UTPI, MAP, PLGF, and SFLT from 30,935, 29,042, 10,123, and 8,264 pregnancies, respectively. The Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median values. Ten-fold cross-validation was used to estimate the performance of screening for PE requiring delivery at < 37 weeks' gestation (preterm-PE) and those delivering at >= 37 weeks (term-PE). The empirical performance was compared with model predictions. RESULTS: In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for preterm-PE than term-PE, and therefore, the performance of screening was inversely related to the gestational age at which delivery become necessary for maternal and/or fetal indications. Combined screening by maternal factors, MAP, UTPI, PLGF, and SFLT predicted 98% (95% confidence interval, 88-100%) of preterm-PE and 49% (95% confidence interval, 42 57%) of term-PE, at a false-positive rate of 5%. These empirical detection rates are compatible with the respective model-based rates of 98% and 54%, but the latter were optimistically biased. CONCLUSION: Combination of maternal factors and biomarkers in the early third trimester could predict nearly all cases of preterm-PE and half of those with term-PE, at 5% false-positive rate. PMID- 26875954 TI - Antepartum and intrapartum interventions to prevent preterm birth and its sequelae. AB - Preterm birth is the main cause of neonatal morbidity and mortality. This review provides an overview of antepartum and intrapartum management of threatened preterm birth. The most effective method to identify women at high risk of delivering within seven days is the combination of cervical length and fetal fibronectin test. Antenatal corticosteroids administered for 48 h improve neonatal outcome. Although tocolysis has been shown to prolong pregnancy, there is no evidence that tocolytic therapy improves neonatal outcomes. Intrapartum administration of magnesium sulfate improves neurologic outcomes, such as cerebral palsy and gross motor function. In women with preterm premature rupture of membranes, prophylactic antibiotic treatment with erythromycin improves short term neonatal outcomes, but proof of long-term benefit is lacking. In threatened preterm birth with intact membranes, prophylactic antibiotic treatment is thought to be harmful. Critical appraisal of the long-term benefits and harms of all these treatments questions their use. PMID- 26875955 TI - Clinical Backgrounds and Outcomes of Elderly Japanese Patients with Gastrointestinal Bleeding. AB - OBJECTIVE: Elderly gastrointestinal bleeding (GIB) patients sometimes cannot be discharged home. In some cases, they die after hemostasis, even following appropriate treatment. This study investigates the clinical backgrounds and outcomes of elderly Japanese GIB patients. METHODS: The medical records of 185 patients (123 men, 62 women; mean age 68.2 years; range 10-99 years) with GIB symptoms who underwent esophagogastroduodenoscopy or colonoscopy to detect or treat the source of GIB were retrospectively reviewed. We compared the outcomes between patients <=70 (n=85) and >70 (n=100) years. The clinical backgrounds of the patients who died or changed hospitals to undergo rehabilitation or receive palliative care were evaluated, as were the association of four factors with these poor outcomes: GIB (re-bleeding or uncontrolled bleeding), endoscopic procedure-related complications, exacerbation of the pre-existing comorbidity, and any complications that were not directly related to GIB. RESULTS: Of the patients <=70 and >70 years of age, three (3.5%) and 17 (17.0%), respectively, were transferred to another hospital (p=0.003). One (1.2%) and five (5.0%), respectively, died (p=0.144). All three patients <=70 years old that changed hospitals did so because their comorbidities became worse. The reasons for changing hospitals in the 17 patients >70 years of age included exacerbation of a pre-existing comorbidity (41.1%, 7/17), other complications (35.4%, 6/17), GIB itself (17.6%, 3/17), and endoscopic procedure-related complications (5.9%, 1/17). CONCLUSION: Although non-elderly and elderly GIB patients had similar mortality rates, many more elderly patients could not be discharged home for various reasons. PMID- 26875956 TI - Unfractionated Heparin during the Interruption of Antiplatelet Therapy for Non cardiac Surgery after Drug-eluting Stent Implantation. AB - OBJECTIVE: Heparin is not recommended to be administered during the interruption of antiplatelet therapy for non-cardiac surgery. However, there are insufficient data to determine the value. The purpose of the present study was to evaluate the clinical results of the administration of unfractionated heparin during the interruption of antiplatelet therapy in non-cardiac surgery patients who had previously undergone drug-eluting stent (DES) implantation. METHODS: We retrospectively identified 210 elective non-cardiac surgical procedures that were performed with the administration of unfractionated heparin during interruption of all antiplatelet therapies in patients who had previously undergone DES implantation. Heparin was administered during the perioperative period in accordance with the local practice guideline at out institution. We examined the clinical outcomes within 30 days of surgery. RESULTS: The mean number of implanted DESs was 2.1+/-1.3. No major adverse cardiac events (including cardiac death, definite stent thrombosis, and non-fatal myocardial infarction) occurred in any of the 210 cases within 30 days of surgery. Four of the 210 cases (1.9%) required reoperation for bleeding within 30 days of surgery. CONCLUSION: Our data showed the potential for the perioperative management with unfractionated heparin administration in Japanese patients who had previously undergone DES implantation who required non-cardiac surgery with the interruption of all antiplatelet therapies. PMID- 26875957 TI - Pleural Effusion in Multiple Myeloma. AB - OBJECTIVE: Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. METHODS: We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. RESULTS: This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-kappa, DSS stage IIIA; ISS stage II. CONCLUSION: The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant blood supply. The routine pleural effusion pathological examination had low sensitivity. Flow cytometry may be more useful for improving the detection rate of MPE. PMID- 26875958 TI - A Feasibility Study of Virtual Reality Exercise in Elderly Patients with Hematologic Malignancies Receiving Chemotherapy. AB - OBJECTIVE: Adherence to rehabilitation exercise is much lower in patients with hematologic malignancies (22.5-45.8%) than in patients with solid tumors (60-85%) due to the administration of more intensive chemotherapeutic regimens in the former. Virtual reality exercise can be performed even in a biological clean room and it may improve the adherence rates in elderly patients with hematologic malignancies. Thus, in this pilot study, we aimed to investigate the feasibility and safety of virtual reality exercise intervention using Nintendo Wii Fit in patients with hematologic malignancies receiving chemotherapy. METHODS: In this feasibility study, 16 hospitalized patients with hematologic malignancies aged >=60 years performed virtual reality exercise for 20 minutes using the Nintendo Wii Fit once a day, five times a week, from the start of chemotherapy until hospital discharge. The adherence rate, safety, and physical and psychological performances were assessed. RESULTS: The adherence rate for all 16 patients was 66.5%. Nine patients completed the virtual reality exercise intervention with 88 sessions, and the adherence rate was 62.0%. No intervention-related adverse effects >Grade 2, according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, were observed. We noted maintenance of the physical performance (e.g., Barthel index, handgrip strength, knee extension strength, one-leg standing time, and the scores of timed up and go test and Instrumental Activities of Daily Living) and psychosocial performance (e.g., score of hospital anxiety and depression scale). CONCLUSION: Virtual reality exercise using the Wii Fit may be feasible, safe and efficacious, as demonstrated in our preliminary results, for patients with hematologic malignancies receiving chemotherapy. PMID- 26875959 TI - Calcification around the Struts of a Sirolimus-eluting Stent Approximately 16 Months after Implantation in an Autopsy Case. AB - Drug-eluting stents (DES) are widely used for the treatment of coronary artery disease, and a sirolimus-eluting stent (SES; Cypher) was the first DES introduced into clinical practice. Although pathological reactions of coronary arteries to SES have been described in autopsy cases, there are few reports regarding calcification of the coronary arteries after SES implantation. The present report describes the findings of an autopsy conducted 16 months after SES implantation that showed remarkable persistent calcification. In addition, previously reported pertinent pathological findings are also described. PMID- 26875961 TI - Hemodialysis Associated with Severe and Unpredictable Hypoglycemia. AB - We herein report the case of a 68-year-old man receiving hemodialysis who developed severe hypoglycemia. He became unconscious and exhibited a blood glucose level below 10 mg/dL. We ruled out the possibility of other causes; however, severe hypoglycemia was observed even after starting glucose injections. The patient developed pneumonia and finally died. Although we conducted an autopsy, there were no specific findings explaining the severe hypoglycemia. We believe that carnitine deficiency was possibly involved in the severe hypoglycemia observed in this case. Physicians should be aware of the possibility of carnitine deficiency and/or severe hypoglycemia, especially in hemodialysis patients with malnutrition. PMID- 26875960 TI - Detecting Cardiac Sarcoidosis with a Right Atrial Mass Using Transthoracic Echocardiography. AB - An asymptomatic 40-year-old woman with a first-degree atrioventricular block presented a right atrial mass in transthoracic echocardiograms. Transesophageal echocardiograms showed abnormally thickened tissue on the interatrial septum, which extended around the aortic annulus. Multimodality examinations demonstrated lesions in the heart, lungs, liver, and spleen, suggesting sarcoidosis. She was diagnosed with cardiac sarcoidosis after we detected granulomas in a lung specimen. A right atrial mass shrunk following steroid therapy. We should therefore consider the possibility of cardiac sarcoidosis when we see wall thickening and a mass echo in the atrium. These signs may point to an early-phase lesion of cardiac sarcoidosis. PMID- 26875962 TI - Renal Light Chain Deposition Associated with the Formation of Intracellular Crystalline Inclusion Bodies in Podocytes: A Rare Case Report. AB - We herein report the case of an elderly woman with bone pain and proteinuria as the main clinical manifestations. The patient was diagnosed with the IgG kappa type of multiple myeloma. Her renal pathology consisted of widespread kappa light chain protein deposition associated with the formation of large quantities of rod like crystals in podocytes. This phenomenon is very rare. We explored the significance of this crystal formation via a detailed and descriptive analysis and also performed a literature review, thus providing data to increase the available information about this type of disease. PMID- 26875964 TI - Primary Pulmonary Synovial Sarcoma Showing a Prolonged Survival with Multimodality Therapy. AB - A 54-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Thoracoscopic lobectomy yielded a diagnosis of primary pulmonary synovial sarcoma according to the histology and SYT-SSX1 gene analyses. Five months after the thoracic surgery, he developed brain metastasis; therefore, we performed resection of the brain metastatic focus followed by radiotherapy. As a local recurrence in the thoracic cavity concurrently emerged, systemic chemotherapy was also administered. These observations indicated that a multidisciplinary approach may be useful against primary pulmonary synovial sarcoma, although there is presently no established therapeutic strategy due to its rarity and highly aggressive nature. PMID- 26875963 TI - Post-Transplant Membranous Nephropathy Associated with Chronic Active Antibody Mediated Rejection and Hepatitis C Infection after Deceased Donor Renal Transplantation. AB - A 53-year-old woman who had undergone deceased donor kidney transplantation twice, at 35 and 43 years of age, presented with renal impairment. She was infected with hepatitis C virus (HCV). The histology of the graft kidney revealed post-transplant membranous nephropathy (MN) with podocytic infolding and antibody mediated rejection (AMR). IgG subclass staining showed fine granular deposits of IgG1 and IgG3, but not IgG4, in the glomerular capillary walls. Panel reactive antibody scores for human leukocyte antigen class I and class II were 92.67% and 66.68%, respectively. Thus, this case of post-transplanted MN was considered to be associated with AMR and HCV infection. PMID- 26875965 TI - Acute Exacerbation of Idiopathic Pulmonary Fibrosis Following Treatment for Cushing's Syndrome. AB - A 64-year-old Japanese man with mild reticular shadows in both lungs developed a lung tumor causing ectopic Cushing's syndrome. He was prescribed an adrenal inhibitor, which controlled his hypercortisolemia. However, he developed acute exacerbation of idiopathic pulmonary fibrosis (IPF) and died within weeks. Previous studies have suggested a dosage reduction of corticosteroids for IPF as a triggering event for acute exacerbation. The present case suggests that IPF coexisting with Cushing's syndrome may have been exacerbated after the correction of hypercortisolemia. Therefore, close monitoring of cortisol levels along with the clinical course of IPF is required in similar cases that require the correction of hypercortisolemia. PMID- 26875966 TI - Occurrence of Donor Cell-derived Lymphoid Blast Crisis 24 Years Following Related Bone Marrow Transplantation for Chronic Myeloid Leukemia. AB - We herein report a unique case of donor cell leukemia (DCL), as donor cell derived lymphoid blast crisis of chronic myeloid leukemia (CML) was observed 24 years after related bone marrow transplantation for CML in the chronic phase. Short tandem repeat testing of the leukemic blast sample revealed full donor chimerism, strongly indicative of DCL. The original donor is healthy with a normal complete blood cell count for the past 24 years. This rare case may provide a precious opportunity to consider not only the underlying mechanism of DCL, but also the pathogenesis of CML. PMID- 26875967 TI - Gamma Heavy Chain Disease with T-cell Large Granular Lymphocytic Leukemia: A Case Report and Review of the Literature. AB - Gamma heavy chain disease (gHCD) is a rare lymphoproliferative disorder characterized by the production of a truncated immunoglobulin heavy chain. Although some cases of gHCD are concurrent with other lymphoid neoplasms, few have been reported. We herein present the case of a 73-year-old woman with gHCD and T-cell large granular lymphocytic leukemia. A multiparameter flow cytometry analysis revealed neoplastic cells that were positive for CD28, a marker of T cell activation, the anti-apoptotic antigen of neoplastic plasma cells, CD38 and CD45. The results of this multiparameter flow cytometry analysis may contribute to furthering the understanding of the clinicopathological features of gHCD. PMID- 26875968 TI - A CSF3R T618I Mutation in a Patient with Chronic Neutrophilic Leukemia and Severe Bleeding Complications. AB - Chronic neutrophilic leukemia (CNL) is a rare form of myeloproliferative neoplasm characterized by the drastic elevation of mature neutrophils. One of the major causes of death among patients with CNL is severe bleeding; however, the difficulty of accurately diagnosing this disease has caused confusion in this field. Recently, somatic mutations of the CSF3R gene have been associated with CNL. This has led to the establishment of more accurate diagnostic criteria for CNL. We herein report a case study of a patient with CNL with a T618I point mutation on the CSF3R gene who showed severe bleeding. PMID- 26875971 TI - Catheter-induced Spasm Presenting with Ventricular Fibrillation. PMID- 26875969 TI - Cardiovascular Instability Preceded by Orolingual Angioedema after Alteplase Treatment. AB - An 87-year-old man taking antihypertensive medications, including 10 mg enalapril, daily visited our hospital complaining of motor aphasia, dysarthria, and right hemiparesis. Magnetic resonance imaging revealed an ischemic lesion in the left frontal lobe including the insular cortex and severe stenosis of the left middle cerebral artery. After he received intravenous alteplase infusion, he developed orolingual angioedema followed by transient bradycardia with subsequent hypotension, resulting in the deterioration of his neurological signs and expansion of the ischemic lesion. Orolingual angioedema after intravenous alteplase infusion may follow cardiovascular instability and disease progression in stroke patients. PMID- 26875972 TI - Dropped Head Syndrome Following Mantle Radiation Therapy. PMID- 26875970 TI - Hypertrophic Pachymeningitis as a Delayed Complication of Granulomatosis with Polyangiitis. AB - A 69-year-old man presented with upper airway symptoms, multiple lung nodules and masses, proteinuria and hematuria, and an increased level of proteinase 3 anti neutrophil cytoplasmic antibody (PR3-ANCA). Granulomatosis with polyangiitis (GPA) was diagnosed by a transbronchial lung biopsy. All of these symptoms were ameliorated and the level of PR3-ANCA declined following treatment with prednisolone and cyclophosphamide. The patient developed a headache 16 months after the onset of symptoms, and contrast-enhanced magnetic resonance imaging showed the thickening of the dura mater, which suggested that hypertrophic pachymeningitis (HP) had developed as a complication of GPA. HP can be a unique complication of GPA at recurrence, and can occur without the relapse of other lesions or an increase in PR3-ANCA level. PMID- 26875973 TI - An Unusual Cause of Hip Pain. PMID- 26875974 TI - Role of codon usage and tRNA changes in rat cytomegalovirus latency and (re)activation. AB - Herpesviruses can remain in their hosts by establishing a latent infection with a low pattern of viral gene expression. Passage from latency to reactivation may occur under particular conditions such as immunosuppressive treatments or during fetal development, and often is accompanied by heavy pathologic sequelae. To investigate the molecular basis underlying herpesvirus latency and (re)activation, codon usage of rat cytomegalovirus was comparatively analyzed with respect to the rat codon usage. Two major points stand out as follows: (i) six codons - GCG (Ala), CCG (Pro), CGG (Arg), CGC (Arg), TCG (Ser), and ACG (Thr) - are rare in rat genes and intensively used in rat cytomegalovirus coding sequences; (ii) in many instances, the codons seldom used by the host are clustered along viral sequences coding for single amino acid repeats such as poly Ala and poly-Thr stretches. The results indicate that rare host codons and their iteration along viral sequences might represent major constraints that lock rat cytomegalovirus translation in its host during the viral latent phase. Consequently, the data also suggest a link between rat cytomegalovirus quiescence/activation and the functional tRNA coadaptation phenomenon. Indeed, increases in minor tRNA species corresponding to rare rat codons mark rat cell proliferation and might rescue difficult viral translational contexts. Ala isoaccepting-tRNA (CGC) is reported as an example. On the whole, the present findings may contribute to explain how the molecular mechanisms that normally control host gene expression can silence/(re)activate viral gene expression, and might address research toward new approaches in anti-viral therapeutics. PMID- 26875975 TI - Yeast Biosensors for Detection of Environmental Pollutants: Current State and Limitations. AB - Yeast biosensors have become suitable tools for the screening and detection of environmental pollutants because of their various advantages compared to other sensing technologies. On the other hand, many limitations remain with regard to their optimal performance and applicability in several contexts, such as low concentration samples and on-site testing. This review summarizes the current state of yeast biosensors, with special focus on screening and assessment of environmental contaminants, discusses both pros and cons, and suggests steps towards their further development and effective use in the environmental assessment. PMID- 26875976 TI - Glycoconjugates and Glycomimetics as Microbial Anti-Adhesives. AB - Microbial adhesion is an essential step in infection and is mediated primarily by protein-carbohydrate interactions. Antagonists of such interactions have become a promising target for anti-adhesive therapy in several infective diseases. Monovalent protein-sugar interactions are often weak, and most successful anti adhesive materials consist of multivalent glycoconjugates. Although often very effective in hampering microbial adhesion, natural epitopes often show limited resistance to enzymatic degradation. The use of carbohydrate mimics (glycomimetics) as a replacement for natural sugars potentially allows higher metabolic stability and also higher selectivity towards the desired protein target. In this review we describe the state of the art in the design and synthesis of glycoconjugates and glycomimetics employed for the construction of anti-adhesive biomaterials. PMID- 26875977 TI - Morphology and N2 Permeance of Sputtered Pd-Ag Ultra-Thin Film Membranes. AB - The influence of the temperature during the growth of Pd-Ag films by PVD magnetron sputtering onto polished silicon wafers was studied in order to avoid the effect of the support roughness on the layer growth. The surfaces of the Pd Ag membrane films were analyzed by atomic force microscopy (AFM), and the results indicate an increase of the grain size from 120 to 250-270 nm and film surface roughness from 4-5 to 10-12 nm when increasing the temperature from around 360 510 K. After selecting the conditions for obtaining the smallest grain size onto silicon wafer, thin Pd-Ag (0.5-2-um thick) films were deposited onto different types of porous supports to study the influence of the porous support, layer thickness and target power on the selective layer microstructure and membrane properties. The Pd-Ag layers deposited onto ZrO2 3-nm top layer supports (smallest pore size among all tested) present high N2 permeance in the order of 10(-6) mol.m(-2).s(-1).Pa(-1) at room temperature. PMID- 26875978 TI - Chemical Characterization and Trypanocidal, Leishmanicidal and Cytotoxicity Potential of Lantana camara L. (Verbenaceae) Essential Oil. AB - Drug resistance in the treatment of neglected parasitic diseases, such as leishmaniasis and trypanosomiasis, has led to the search and development of alternative drugs from plant origins. In this context, the essential oil extracted by hydro-distillation from Lantana camara leaves was tested against Leishmania braziliensis and Trypanosoma cruzi. The results demonstrated that L. camara essential oil inhibited T. cruzi and L. braziliensis with IC50 of 201.94 MUg/mL and 72.31 MUg/mL, respectively. L. camara essential oil was found to be toxic to NCTC929 fibroblasts at 500 MUg/mL (IC50 = 301.42 MUg/mL). The composition of L. camara essential oil analyzed by gas chromatography-mass spectrometry (GC/MS) revealed large amounts of (E)-caryophyllene (23.75%), biciclogermacrene (15.80%), germacrene D (11.73%), terpinolene (6.1%), and sabinene (5.92%), which might be, at least in part, responsible for its activity. Taken together, our results suggest that L. camara essential oil may be an important source of therapeutic agents for the development of alternative drugs against parasitic diseases. PMID- 26875979 TI - Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates. AB - Based on the presence of carbamoyl moiety, twenty salicylanilide N,N disubstituted (thio)carbamates were investigated using Ellman's method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 uM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 uM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 uM). Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization. PMID- 26875983 TI - Local Tiled Deep Networks for Recognition of Vehicle Make and Model. AB - Vehicle analysis involves license-plate recognition (LPR), vehicle-type classification (VTC), and vehicle make and model recognition (MMR). Among these tasks, MMR plays an important complementary role in respect to LPR. In this paper, we propose a novel framework for MMR using local tiled deep networks. The frontal views of vehicle images are first extracted and fed into the local tiled deep networks for training and testing. A local tiled convolutional neural network (LTCNN) is proposed to alter the weight sharing scheme of CNN with local tiled structure. The LTCNN unties the weights of adjacent units and then ties the units k steps from each other within a local map. This architecture provides the translational, rotational, and scale invariance as well as locality. In addition, to further deal with the colour and illumination variation, we applied the histogram oriented gradient (HOG) to the frontal view of images prior to the LTCNN. The experimental results show that our LTCNN framework achieved a 98% accuracy rate in terms of vehicle MMR. PMID- 26875981 TI - Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress. AB - Selenium is an essential micronutrient for humans. Much of selenium's beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells. PMID- 26875982 TI - Overexpression of Glucocorticoid Receptor beta Enhances Myogenesis and Reduces Catabolic Gene Expression. AB - Unlike the glucocorticoid receptor alpha (GRalpha), GR beta (GRbeta) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRalpha as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRbeta causes glucocorticoid resistance, targeting GRbeta may be beneficial in impairing muscle loss as a result of GRalpha activity. The purpose of this study was to determine how the overexpression of GRbeta affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRbeta in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRbeta overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRbeta overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRbeta had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRbeta may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRbeta levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids. PMID- 26875980 TI - Endocannabinoids as Guardians of Metastasis. AB - Endocannabinoids including anandamide and 2-arachidonoylglycerol are involved in cancer pathophysiology in several ways, including tumor growth and progression, peritumoral inflammation, nausea and cancer pain. Recently we showed that the endocannabinoid profiles are deranged during cancer to an extent that this manifests in alterations of plasma endocannabinoids in cancer patients, which was mimicked by similar changes in rodent models of local and metastatic cancer. The present topical review summarizes the complexity of endocannabinoid signaling in the context of tumor growth and metastasis. PMID- 26875984 TI - Suppressive Effects of the Site 1 Protease (S1P) Inhibitor, PF-429242, on Dengue Virus Propagation. AB - Dengue virus (DENV) infection causes one of the most widespread mosquito-borne diseases in the world. Despite the great need, effective vaccines and practical antiviral therapies are still under development. Intracellular lipid levels are regulated by sterol regulatory elements-binding proteins (SREBPs), which are activated by serine protease, site 1 protease (S1P). Small compound PF-429242 is known as a S1P inhibitor and the antivirus effects have been reported in some viruses. In this study, we examined the anti-DENV effects of PF-429242 using all four serotypes of DENV by several primate-derived cell lines. Moreover, emergence of drug-resistant DENV mutants was assessed by sequential passages with the drug. DENV dependency on intracellular lipids during their infection was also evaluated by adding extracellular lipids. The addition of PF-429242 showed suppression of viral propagation in all DENV serotypes. We showed that drug-resistant DENV mutants are unlikely to emerge after five times sequential passages through treatment with PF-429242. Although the levels of intracellular cholesterol and lipid droplets were reduced by PF-429242, viral propagations were not recovered by addition of exogenous cholesterol or fatty acids, indicating that the reduction of LD and cholesterol caused by PF-429242 treatment is not related to its mechanism of action against DENV propagation. Our results suggest that PF 429242 is a promising candidate for an anti-DENV agent. PMID- 26875985 TI - Genetic Variability of HIV-1 for Drug Resistance Assay Development. AB - A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 reverse transcriptase (RT) sequences from the Stanford HIV Drug Resistance Database originating from six LMIC regions. We characterized the variability in a 27-nucleotide window surrounding six clinically important drug resistance mutations (DRMs) at positions 65, 103, 106, 181, 184, and 190. The number of distinct codons at each DRM position ranged from four at position 184 to 11 at position 190. Depending on the mutation, between 11 and 15 of the 24 flanking nucleotide positions were variable. Nonetheless, most flanking sequences differed from a core set of 10 flanking sequences by just one or two nucleotides. Flanking sequence variability was also lower in each LMIC region compared with overall variability in all regions. We also describe an online program that we developed to perform similar analyses for mutations at any position in RT, protease, or integrase. PMID- 26875987 TI - Cholesterol Promotes Interaction of the Protein CLIC1 with Phospholipid Monolayers at the Air-Water Interface. AB - CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. The regulatory role of cholesterol in the ion-channel activity of CLIC1 in tethered lipid bilayers was previously assessed using impedance spectroscopy. Here we extend this investigation by evaluating the influence of cholesterol on the spontaneous membrane insertion of CLIC1 into Langmuir film monolayers prepared using 1-palmitoyl-2-oleoylphosphatidylcholine, 1-palmitoyl-2-oleoyl-sn glycero-3-phospho-ethanolamine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L serine alone or in combination with cholesterol. The spontaneous membrane insertion of CLIC1 was shown to be dependent on the presence of cholesterol in the membrane. Furthermore, pre-incubation of CLIC1 with cholesterol prior to its addition to the Langmuir film, showed no membrane insertion even in monolayers containing cholesterol, suggesting the formation of a CLIC1-cholesterol pre complex. Our results therefore suggest that CLIC1 membrane interaction involves CLIC1 binding to cholesterol located in the membrane for its initial docking followed by insertion. Subsequent structural rearrangements of the protein would likely also be required along with oligomerisation to form functional ion channels. PMID- 26875988 TI - Making the practically impossible "Merely difficult"--Cryogenic FIB lift-out for "Damage free" soft matter imaging. AB - The preparation of thinned lamellae from bulk samples for transmission electron microscopy (TEM) analysis has been possible in the focussed ion beam scanning electron microscope (FIB-SEM) for over 20 years via the in situ lift-out method. Lift-out offers a fast and site specific preparation method for TEM analysis, typically in the field of materials science. More recently it has been applied to a low-water content biological sample (Rubino 2012). This work presents the successful lift-out of high-water content lamellae, under cryogenic conditions (cryo-FIB lift-out) and using a nanomanipulator retaining its full range of motion, which are advances on the work previously done by Rubino (2012). Strategies are explored for maintaining cryogenic conditions, grid attachment using cryo-condensation of water and protection of the lamella when transferring to the TEM. PMID- 26875989 TI - A sustainable approach to training nurses in acute care skills in a resource limited setting (Network for Intensive Care Skills Training, NICST). PMID- 26875990 TI - Systematic review and meta-analysis of hemodynamic-directed feedback during cardiopulmonary resuscitation in cardiac arrest. AB - BACKGROUND/OBJECTIVE: Physiologic monitoring of resuscitative efforts during cardiac arrest is gaining in importance, as it provides a real-time window into the cellular physiology of patients. The aim of this review is to assess the quality of evidence surrounding the use of physiologic monitoring to guide cardiopulmonary resuscitation (CPR), and to examine whether the evidence demonstrates an improvement in patient outcome when comparing hemodynamic directed CPR versus standard CPR. METHODS: Studies were obtained through a search of the PubMed, Embase and Cochrane databases. Peer-reviewed randomized trials, case-control studies, systematic reviews, and cohort studies that titrated CPR to physiologic measures, compared results to standard CPR, and examined patient outcome were included. RESULTS: Six studies met inclusion criteria, with all studies conducted in animal populations. Four studies examined the effects of hemodynamic-directed CPR on survival, with 35/37 (94.6%) animals surviving in the hemodynamic-directed CPR groups and 12/35 (34.3%) surviving in the control groups (p<0.001). Two studies examined the effects of hemodynamic-directed CPR on ROSC, with 22/30 (73.3%) achieving ROSC in the hemodynamic-directed CPR group and 19/30 (63.3%) achieving ROSC in the control group (p=0.344). DISCUSSION/CONCLUSION: These results suggest a trend in survival from hemodynamic-directed CPR over standard CPR, however the small sample size and lack of human data make these results of limited value. Future human studies examining hemodynamic-directed CPR versus current CPR standards are needed to enhance our understanding of how to effectively use physiologic measures to improve resuscitation efforts and ultimately incorporate concrete targets into international resuscitation guidelines. PMID- 26875991 TI - Defibrillation success during different phases of the mechanical chest compression cycle. AB - INTRODUCTION: Animal studies indicate higher termination of VF/VT (TOF) rates after shocks delivered during the decompression phase of the compression cycle for manual and mechanical CPR. We investigated TOF for shocks delivered in different compression cycle phases during load distributing band (LDB) mechanical CPR in the CIRC trial. METHODS: Shocks were retrospectively categorized as delivered during the compression, decompression, or relaxation phase of LDB compressions using transthoracic impedance data. Shocks delivered when the LDB device was paused, were used as controls. The first shock and the first up-to three shocks (first shocks plus shocks two and three if given) from patients with initial VF/VT and LDB CPR prior to shock were grouped according to compression cycle phase. TOF rates for these groups versus the control group were analyzed using logistic regression for first shocks and the general estimating equations (GEE) model for the up-to-three shocks. Adjustments were made for bystander CPR, witnessed arrest, defibrillator shock energy and transthoracic impedance. RESULTS: Among 244 first shocks and 685 up-to-three shocks TOF success rates were lower (p<0.05 and p<0.02) for shocks given during the compression phase (72% and 71% respectively) than for control shocks given during compression pauses (86% and 82% respectively). Decompression and relaxation phase shocks had TOF rates not different from the controls. CONCLUSION: Shocks delivered in the compression phase of LDB chest compressions had lower TOF rates than shocks delivered while pausing the LDB device. More research is needed to see how defibrillation during chest compressions affect ROSC and survival. PMID- 26875992 TI - Measuring teamwork performance: Validity testing of the Team Emergency Assessment Measure (TEAM) with clinical resuscitation teams. AB - AIM: To test the resuscitation non-technical Team Emergency Assessment Measure (TEAM) for feasibility, validity and reliability, in two Australian Emergency Departments (ED). BACKGROUND: Non-technical (teamwork) skills have been identified as inadequate and as such have a significant impact on patient safety. Valid and reliable teamwork assessment tools are an important element of performance assessment and debriefing processes. METHODS: A quasi experimental design based on observational ratings of resuscitation non-technical skills in two metropolitan ED. Senior nursing staff rated 106 adult resuscitation team events over a ten month period where three or more resuscitation team members attended. Resuscitation events, team performance and validity and reliability data was collected for the TEAM. RESULTS: Most rated events were for full cardiac resuscitation (43%) with 3-15 team members present for an average of 45 min. The TEAM was found to be feasible and quickly completed with minimal or no training. Discriminant validity was good as was internal consistency with a Cronbach alpha of 0.94. Uni-dimensional and concurrent validity also reached acceptable standards, 0.94 and >0.63 (p=<0.001), respectively, and a single 'teamwork' construct was identified. Non-technical skills overall were good but leadership was rated notably lower than task and teamwork performance indicating a need for leadership training. CONCLUSION: The TEAM is a feasible, valid and reliable non technical assessment measure in simulated and real clinical settings. Emergency teams need to develop leadership skills through training and reflective debriefing. PMID- 26875993 TI - Dissecting the role of redox signaling in neuronal development. AB - The generation of abnormally high levels of reactive oxygen species (ROS) is linked to cellular dysfunction, including neuronal toxicity and neurodegeneration. However, physiological ROS production modulates redox sensitive roles of several molecules such as transcription factors, signaling proteins, and cytoskeletal components. Changes in the functions of redox sensitive proteins may be important for defining key aspects of stem cell proliferation and differentiation, neuronal maturation, and neuronal plasticity. In neurons, most of the studies have been focused on the pathological implications of such modifications and only very recently their essential roles in neuronal development and plasticity has been recognized. In this review, we discuss the participation of NADPH oxidases (NOXs) and a family of protein methionine sulfoxide oxidases, named molecule interacting with CasLs, as regulated enzymatic sources of ROS production in neurons, and describes the contribution of ROS signaling to neurogenesis and differentiation, neurite outgrowth, and neuronal plasticity. We review the role of reactive oxygen species (ROS) in neurogenesis, axon growth, and guidance and NMDA-receptor-mediated plasticity, LTP, and memory. ROS participation is presented in the context of NADPH oxidase and MICAL functions and their importance for brain functions. PMID- 26875995 TI - Endothelial chimerism in chronic sclerotic-type chronic graft-versus-host disease (GVHD) and GVHD-associated angiomatosis. AB - Graft-versus-host disease-associated angiomatosis (GVHD-AA) is an uncommon manifestation of chronic GVHD consisting of friable vascular proliferations. Using fluorescence in situ hybridization, we demonstrate the presence of donor derived endothelial cells within areas of GVHD-AA. This is the first documented occurrence of a benign neoplastic growth in relationship to a form of chronic GVHD. PMID- 26875994 TI - A controlled spinal cord contusion for the rhesus macaque monkey. AB - Most in vivo spinal cord injury (SCI) experimental models use rodents. Due to the anatomical and functional differences between rodents and humans, reliable large animal models, such as non-human primates, of SCI are critically needed to facilitate translation of laboratory discoveries to clinical applications. Here we report the establishment of a controlled spinal contusion model that produces severity-dependent functional and histological deficits in non-human primates. Six adult male rhesus macaque monkeys underwent mild to moderate contusive SCI using 1.0 and 1.5mm tissue displacement injuries at T9 or sham laminectomy (n=2/group). Multiple assessments including motor-evoked potential (MEP), somatosensory-evoked potential (SSEP), MR imaging, and monkey hindlimb score (MHS) were performed. Monkeys were sacrificed at 6 months post-injury, and the lesion area was examined for cavitation, axons, myelin, and astrocytic responses. The MHS demonstrated that both the 1.0 and 1.5mm displacement injuries created discriminative neurological deficits which were severity-dependent. The MEP response rate was depressed after a 1.0mm injury and was abolished after a 1.5mm injury. The SSEP response rate was slightly decreased following both the 1.0 and 1.5mm SCI. MRI imaging demonstrated an increase in T2 signal at the lesion site at 3 and 6months, and diffusion tensor imaging (DTI) tractography showed interrupted fiber tracts at the lesion site at 4h and at 6 months post-SCI. Histologically, severity-dependent spinal cord atrophy, axonal degeneration, and myelin loss were found after both injury severities. Notably, strong astrocytic gliosis was not observed at the lesion penumbra in the monkey. In summary, we describe the development of a clinically-relevant contusive SCI model that produces severity-dependent anatomical and functional deficits in non-human primates. Such a model may advance the translation of novel SCI repair strategies to the clinic. PMID- 26875986 TI - The Deep Correlation between Energy Metabolism and Reproduction: A View on the Effects of Nutrition for Women Fertility. AB - In female mammals, mechanisms have been developed, throughout evolution, to integrate environmental, nutritional and hormonal cues in order to guarantee reproduction in favorable energetic conditions and to inhibit it in case of food scarcity. This metabolic strategy could be an advantage in nutritionally poor environments, but nowadays is affecting women's health. The unlimited availability of nutrients, in association with reduced energy expenditure, leads to alterations in many metabolic pathways and to impairments in the finely tuned inter-relation between energy metabolism and reproduction, thereby affecting female fertility. Many energetic states could influence female reproductive health being under- and over-weight, obesity and strenuous physical activity are all conditions that alter the profiles of specific hormones, such as insulin and adipokines, thus impairing women fertility. Furthermore, specific classes of nutrients might affect female fertility by acting on particular signaling pathways. Dietary fatty acids, carbohydrates, proteins and food-associated components (such as endocrine disruptors) have per se physiological activities and their unbalanced intake, both in quantitative and qualitative terms, might impair metabolic homeostasis and fertility in premenopausal women. Even though we are far from identifying a "fertility diet", lifestyle and dietary interventions might represent a promising and invaluable strategy to manage infertility in premenopausal women. PMID- 26875996 TI - Diagnosis, pathophysiology, and treatment of photophobia. AB - Photophobia, an abnormal intolerance to light, is associated with a number of ophthalmic and neurologic conditions. In the presence of normal neurologic and ophthalmologic examinations, the most common conditions associated with photophobia are migraine, blepharospasm, and traumatic brain injury. Recent evidence indicates that the intrinsically photosensitive retinal ganglion cells play a key role in the pathophysiology of photophobia. Although pharmacologic manipulation of intrinsically photosensitive retinal ganglion cells and the neural pathways that mediate photophobia may be possible in the future, current therapies are directed at the underlying cause of the photophobia and optical modulation of these cells and pathways. PMID- 26875997 TI - Comparison of cell-based and PCR-based assays as methods for measuring infectivity of Tulane virus. AB - In this study, we used Tulane virus (TV) as a surrogate for HuNoV to evaluate for correlation between two cell-based assays and three PCR-based assays. Specifically, the cell-based plaque and TCID50 assays measure for infectious virus particles, while the PCR-based RNase exposure, porcine gastric mucin in situ-capture qRT-PCR (PGM-ISC-qRT-PCR), and antibody in-situ-capture qRT-PCR (Ab ISC-qRT-PCR) assays measure for an amplicon within encapsidated viral genome. Ten batches of viral stocks ranging from 3.41 * 10(5) to 6.67 * 10(6) plaque forming units (PFUs) were used for side by side comparison with PFU as a reference. The results indicate that one PFU was equivalent to 6.69 +/- 2.34 TCID50 units, 9.75 +/- 10.87 RNase-untreated genomic copies (GCs), 2.87 +/- 3.05 RNase-treated GCs, 0.07 +/- 0.07 PGM-ISC-qRT-PCR GCs, and 0.52 +/- 0.39 Ab-ISC-qRT-PCR GCs. We observed that while the cell-based assays were consistent with each other, the TCID50 assay was more sensitive than the plaque assay. In contrast, the PCR-based assays were not always consistent with the cell-based assays. The very high variations in GCs as measured by both ISC-RT-qPCR assays made them difficult to correlate against the relatively small variations (<20-fold) in the PFUs or TCID50 units as measured by the cell-based assays. PMID- 26875998 TI - Akkermansia muciniphila and its role in regulating host functions. AB - Akkermansia muciniphila is an intestinal bacterium that was isolated a decade ago from a human fecal sample. Its specialization in mucin degradation makes it a key organism at the mucosal interface between the lumen and host cells. Although it was isolated quite recently, it has rapidly raised significant interest as A. muciniphila is the only cultivated intestinal representative of the Verrucomicrobia, one of the few phyla in the human gut that can be easily detected in phylogenetic and metagenome analyses. There has also been a growing interest in A. muciniphila, due to its association with health in animals and humans. Notably, reduced levels of A. muciniphila have been observed in patients with inflammatory bowel diseases (mainly ulcerative colitis) and metabolic disorders, which suggests it may have potential anti-inflammatory properties. The aims of this review are to summarize the existing data on the intestinal distribution of A. muciniphila in health and disease, to provide insight into its ecology and its role in founding microbial networks at the mucosal interface, as well as to discuss recent research on its role in regulating host functions that are disturbed in various diseases, with a specific focus on metabolic disorders in both animals and humans. PMID- 26875999 TI - Impact of highly active antiretroviral therapy on nutritional and immunologic status in HIV-infected children in the low-income country of Ethiopia. AB - OBJECTIVE: HIV/AIDS and malnutrition combine to undermine the immunity of individuals and are inextricably interrelated. Although the effect of highly active antiretroviral therapy (HAART) on growth in HIV-infected children is well known, the influence of prior nutritional and immunologic status on the response to HAART is not well documented. The aim of the present study was to determine the effects of HAART on nutritional and immunological status in HIV-infected children in the low-income country of Ethiopia. METHODS: A multicenter, retrospective cohort study was conducted on HIV-infected children receiving antiretroviral therapy at the pediatric units of public hospitals in Addis Ababa (Black Lion, Zewditu, Yekatit 12 and ALERT hospitals), Ethiopia. Nutritional status was defined as stunting (height-for-age Z score [HAZ] <-2), wasting (weight-for-height Z score [WHZ] <-2), and underweight (weight-for-age Z score [WAZ] <-2). Multivariable logistic regression was used to analyze factors associated with treatment success and to establish whether growth (baseline nutritional status) in children predicts immunologic outcomes. In all, 556 HIV infected children receiving HAART from January 2008 to December 2009 were included in this study. RESULTS: Over the 24-mo follow-up period, the study showed that the immunologic recovery of stunted and underweight children, regardless of their baseline nutritional status, responded equally to treatment. However, wasted children showed less immunologic recovery at the different follow up visits. Predictors of positive shift in WHZ after 24 mo of follow-up were advanced disease stage (World Health Organization clinical stages 3 and 4) with odds ratio (OR), 0.25 (95% confidence interval [CI], 0.34-0.99; P = 0.045) and baseline severe underweight OR, 0.19 (95% CI, 0.09-0.56; P = 0.003). The independent predictors of positive shift of growth shift in WAZ over 24 mo were lower baseline age (<36 mo) with OR, 0.21 (95% CI, 0.04-0.90; P = 0.036) and baseline moderate underweight itself with OR, 0.11 (95% CI, 0.05-0.25; P = 0.0001) were predictors of positive shift (shift to normal). CONCLUSION: Despite the apparent growth response in HIV-infected children after initiation of HAART, moderate and severe underweight are both independent predictors of a positive shift. The latter suggests that children on HAART require nutritional supplementation, especially during the early initiation of HAART. PMID- 26876000 TI - Indices of dietary fat quality during midpregnancy is associated with gestational diabetes. AB - OBJECTIVE: To investigate the relationship between gestational diabetes mellitus (GDM) and the usual intake of fatty acids and indices of dietary fat quality [the atherogenicity (AI) and thrombogenicity indices (TI), and the ratios of hypo-and hypercholesterolemic (hH), ?n-3/?n-6, and polyunsaturated/saturated fatty acids (P:S)], during mid-pregnancy. METHODS: 799 adult pregnant women living in Ribeirao Preto, SP, Brazil were screened and accepted for this cross-sectional GDM study. The Multiple Source Method was used to estimate participants' usual diet, using two 24-hour dietary recalls during mid-pregnancy. Diagnosis of GDM was defined by the American Diabetes Association criteria of 2015. Logistic regression analysis were used to assess the association between GDM and dietary fat, adjusted for age, education, parity, gestational age at the time of the interview, pre-pregnancy and current BMI, prior GDM, family history of diabetes, smoking, physical activity, energy, fiber, and fatty acids. RESULTS: The mean (standard deviation) age of the women was 28 (5) years, and 19% had GDM. After multiple adjustments, inverse associations between the highest tertile of ?n-3 fatty acids intake [0.21 (0.08-0.56)], alpha-linolenic intake [0.15 (0.05-0.42)], and GDM were found. A positive association between GDM and the highest tertile of TI [2.66 (1.34-5.29)], and a negative association with the highest tertile of hH ratio [0.41 (0.22-0.77)], were observed. No association between GDM and other indices of dietary fat quality were found. CONCLUSION: The quality of dietary fat during pregnancy is strongly associated with GDM. Randomized clinical trial are needed to confirm these findings. PMID- 26876001 TI - Association of anti-RNA polymerase III antibody and silicone breast implants in patients with systemic sclerosis. AB - Systemic sclerosis (SSc) is believed to be caused by a complex interplay between genetic factors and environmental influences. Although silicone has been considered to be a candidate of environmental agents, clinical data presented so far fail to show a significant association between silicone breast implant (SBI) and the development of SSc. Because we recently experienced two consecutive SSc patients with anti-RNA polymerase III (RNAP III) antibody who underwent SBI, we here investigated the association of SBI history with the development of SSc positive for anti-RNAP III antibody. Among 262 Japanese SSc patients, of note, the frequency of SBI history was significantly higher in the anti-RNAP III antibody group (16.0% [4/25]) than in the anti-topoisomerase I antibody group (0% [0/87], P < 0.005) and in the anticentromere antibody group (1.2% [2/150], P < 0.005). These results suggest that SBI could influence the development of SSc in a certain subset of patients with anti-RNAP III antibody. PMID- 26876003 TI - Expression of active chimeric-tissue plasminogen activator in tobacco hairy roots, identification of a DNA aptamer and purification by aptamer functionalized MWCNTs chromatography. AB - Tissue-type plasminogen activator (tPA) is a serine protease that plays a crucial role in the fibrinolytic system. We increased the activity of tPA by splicing the active site of dodder-cuscutain gene to human tPA. The chimeric cDNA of tPA was constructed by Splicing by Overlap Extension Polymerase Chain Reaction (SOEing PCR) method and transferred to the hairy roots of tobacco using different strains of Agrobacterium rhizogenes. Chimeric-tPA was purified by lysine-sepharose chromatography and specific aptamers were designed using SELEX method. Multi wall carbon nanotubes were functionalized with selected aptamers, packed in a column, and used for purification. The results demonstrated that selected aptamer having KD values of 0.320 nM and IC50 of 28.9 nM possessed good affinity to tPA, and the chimeric-tPA was properly purified by aptamer-chromatography. Hairy roots expressing chimeric-tPA and normal-tPA produced 900 and 450 ngmg-1 of total protein, respectively. The activities of chimeric-tPA and normal-tPA were 90 and 60 IUml-1, respectively. Compared to the normal-tPA, chimeric-tPA showed more activity. PMID- 26876002 TI - Molecular characterization of IFN-T expressed in buffalo embryonic trophoblasts and expression of recombinant BuIFN-T1a2 and BuIFN-T8 isoforms in E. coli. AB - Interferon tau (IFN-T) acts as a signaling molecule for maternal recognition of pregnancy (MRP) in ruminants. Aim of the present study was to identify various Buffalo Interferon tau (BuIFN-T) transcripts in buffalo trophoblast, phylogenetic comparison of these sequences with known mRNA sequences of buffalo, bovine, caprine and ovine and to express and purify the recombinant BuIFN-T (rBuIFN-T) isoforms. Following RNA extraction from trophectodermal cells, RT-PCR was performed using Ifn-t gene specific primers. 13 distinct cDNA variants encoding eight different BuIFN-T proteins were identified. BuIFN-T1a2 and BuIFN-T8 were expressed in prokaryotic expression system at 37 degrees C, 25 degrees C and 16 degrees C with 1 mM IPTG for 12 h and the recombinant proteins expressed at 16 degrees C were partially purified by Immobilised Metal Affinity Chromatography (IMAC). BuIFN-T isoforms have greater nucleotide and amino acid homology with caprine (98-100%, 96-100%), ovine (94-97%, 90-95%) and bovine (89.6-90.6%, 82 86%). These novel BuIFN-T isoforms contained pronounced nucleotide and amino acid sequence identity with one another (99.1-99.8%, 98-99%) but moderate sequence identity with previously identified buffalo IFN-T (90-92%, 82-86%). Solubility of expressed recombinant isoforms (rBuIFN-T1a2 and rBuIFN-T8) was highest at 16 degrees C. In conclusion, 13 distinct Ifn-t gene variants exist in trophectoderm of in vitro developed buffalo blastocysts that encode eight different proteins. rBuIFN-T1a2 and rBuIFN-T8 were successfully expressed in soluble form in Escherichia coli expression system at 16 degrees C with 1 mM IPTG and the resulting recombinant proteins were partially purified by IMAC. PMID- 26876004 TI - Vancomycin resistant Enterococcus spp. from crows and their environment in metropolitan Washington State, USA: Is there a correlation between VRE positive crows and the environment? AB - Vancomycin-resistant enterococci [VRE] have been isolated from municipal, hospital and agricultural wastewater, recreational beaches, wild animals, birds and food animals around the world. In this study, American crows (Corvus brachyrhynchos) from sewage treatment plants (WWTP), dairy farms, and a large roost in a restored wetland with corresponding environmental samples were cultured for VRE. A total of 245 samples [156 crows, 89 environmental] were collected and screened for acquired vanA, vanB and/or intrinsic vanC1 genes. Samples were enriched overnight in BHI supplemented with 20MUg/mL aztreonam, 4MUg/mL vancomycin and plated on m-Enterococcus agar media supplemented with 6MUg/mL vancomycin. Selected colonies were grown on BHI media supplemented with 18MUg/mL vancomycin. Of these, 24.5% of the crow and 55% the environmental/cow samples were VRE positive as defined by Enterococcus spp. able to grow on media supplemented with 18MUg/mL vancomycin. A total of 122 VRE isolates, 43 crow and 79 environmental isolates were screened, identified to species level using 16S sequencing and further characterized. Four vanA E. faecium and multiple vanC1 E. gallinarum were identified from crows isolated from three sites. E. faecium vanA and E. gallinarum vanC1 along with other Enterococcus spp. carrying vanA, vanB, vanC1 were isolated from three environments. All enterococci were multidrug resistant. Crows were more likely to carry vanA E. faecium than either the cow feces or wetland waters/soils. Comparing E. gallinarum vanC1 from crows and their environment would be useful in determining whether crows share VRE strains with their environment. PMID- 26876006 TI - Physiologic effect of repeated adrenaline (epinephrine) doses during cardiopulmonary resuscitation in the cath lab setting: A randomised porcine study. AB - BACKGROUND: This porcine study was designed to explore the effects of repetitive intravenous adrenaline doses on physiologic parameters during CPR. METHODS: Thirty-six adult pigs were randomised to four injections of: adrenaline 0.02 mg(kgdose)(-1), adrenaline 0.03 mg(kgdose)(-1) or saline control. The effect on systolic, diastolic and mean arterial blood pressure, cerebral perfusion pressure (CePP), end tidal carbon dioxide (ETCO2), arterial oxygen saturation via pulse oximetry (SpO2), cerebral tissue oximetry (SctO2), were analysed immediately prior to each injection and at peak arterial systolic pressure and arterial blood gases were analysed at baseline and after 15 min. RESULT: In the group given 0.02 mg(kgdose)(-1), there were increases in all arterial blood pressures at all 4 pressure peaks but CePP only increased significantly after peak 1. A decrease in ETCO2 following peak 1 and 2 was observed. SctO2 and SpO2 were lowered following injection 2 and beyond. In the group given a 0.03 mg(kgdose)(-1), all ABP's increased at the first 4 pressure peaks but CePP only following 3 pressure peaks. Lower ETCO2, SctO2 and SpO2 were seen at peak 1 and beyond. In the two adrenaline groups, pH and Base Excess were lower and lactate levels higher compared to baseline as well as compared to the control. CONCLUSION: Repetitive intravenous adrenaline doses increased ABP's and to some extent also CePP, but significantly decreased organ and brain perfusion. The institutional protocol number: Malmo/Lund Committee for Animal Experiment Ethics, approval reference number: M 192-10. PMID- 26876005 TI - Endocardial Remodeling in Heart Failure Patients with Impaired and Preserved Left Ventricular Systolic Function--A Magnetic Resonance Image Study. AB - Left ventricular (LV) trabeculation has been studied in certain forms of cardiomyopathy. However, the changes of LV endocardial trabeculation during the remodeling process leading to heart failure (HF) are unclear. Seventy-four patients with systolic heart failure (SHF), 65 with heart failure with preserved ejection fraction (HFpEF) and 61 without HF were prospectively enrolled. All subjects received magnetic resonance imaging (MRI) study including cine, T1 and late gadolinium enhancement (LGE) images. Trabecular-papillary muscle (TPM) mass, fractal dimension (FD) and extracellular volume (ECV) were derived. The results showed that TPM mass index was higher in patients with SHF than that in patients with HFpEF and non-HF. The TPM mass-LV mass ratio (TPMm/LVM) was higher in SHF group than that in HFpEF and non-HF. FD was not different among groups. The presence of LGE was inversely associated with TPM mass index and TPMm/LVM while the ECV were positively associated with TPMm/LVM. The FD was positively associated with LV chamber size. In conclusion, TPM increases in patients with SHF and are probably related to myocardial cell hypertrophy and fibrotic repair during remodeling. The FD increases with the dilatation of LV chamber but remain unchanged with the deterioration of LV function. PMID- 26876007 TI - Nonrandom seedling establishment corresponds with distance-dependent decline in mycorrhizal abundance in two terrestrial orchids. AB - In plant species that critically rely on mycorrhizal symbionts for germination and seedling establishment, distance-dependent decline of mycorrhizal fungi in the soil can be hypothesized to lead to significant spatial clustering as a result of nonrandom spatial patterns of seedling establishment. To test this hypothesis, we investigated the abundance and distribution of mycorrhizal fungi in the soil and how they relate to spatial patterns of adults and seedling recruitment in two related orchid species. We combined assessments of spatial variation in fungal abundance using quantitative PCR (qPCR) with spatial point pattern analyses based on long-term demographic data and cluster point process models. qPCR analyses showed that fungal abundance declined rapidly with distance from the adult host plants. Spatial point pattern analyses showed that successful recruitment in both species was clustered significantly around adult plants and that the decline in the neighborhood density of recruits around adults coincided with the decline of fungal abundance around adult plants. Overall, these results indicate that the distribution and abundance of fungal associates in the soil may have a strong impact on the aboveground distribution of its partner. PMID- 26876009 TI - Determination of critical diameters for intrinsic carrier diffusion-length of GaN nanorods with cryo-scanning near-field optical microscopy. AB - Direct measurements of carrier diffusion in GaN nanorods with a designed InGaN/GaN layer-in-a-wire structure by scanning near-field optical microscopy (SNOM) were performed at liquid-helium temperatures of 10 K. Without an applied voltage, intrinsic diffusion lengths of photo-excited carriers were measured as the diameters of the nanorods differ from 50 to 800 nm. The critical diameter of nanorods for carrier diffusion is concluded as 170 nm with a statistical approach. Photoluminescence spectra were acquired for different positions of the SNOM tip on the nanorod, corresponding to the origins of the well-defined luminescence peaks, each being related to recombination-centers. The phenomenon originated from surface oxide by direct comparison of two nanorods with similar diameters in a single map has been observed and investigated. PMID- 26876008 TI - Periodic, Quasi-periodic and Chaotic Dynamics in Simple Gene Elements with Time Delays. AB - Regulatory gene circuit motifs play crucial roles in performing and maintaining vital cellular functions. Frequently, theoretical studies of gene circuits focus on steady-state behaviors and do not include time delays. In this study, the inclusion of time delays is shown to entirely change the time-dependent dynamics for even the simplest possible circuits with one and two gene elements with self and cross regulations. These elements can give rise to rich behaviors including periodic, quasi-periodic, weak chaotic, strong chaotic and intermittent dynamics. We introduce a special power-spectrum-based method to characterize and discriminate these dynamical modes quantitatively. Our simulation results suggest that, while a single negative feedback loop of either one- or two-gene element can only have periodic dynamics, the elements with two positive/negative feedback loops are the minimalist elements to have chaotic dynamics. These elements typically have one negative feedback loop that generates oscillations, and another unit that allows frequent switches among multiple steady states or between oscillatory and non-oscillatory dynamics. Possible dynamical features of several simple one- and two-gene elements are presented in details. Discussion is presented for possible roles of the chaotic behavior in the robustness of cellular functions and diseases, for example, in the context of cancer. PMID- 26876010 TI - The right hemisphere is dominant in organization of visual search-A study in stroke patients. AB - Cancellation tasks are widely used for diagnosis of lateralized attentional deficits in stroke patients. A disorganized fashion of target cancellation has been hypothesized to reflect disturbed spatial exploration. In the current study we aimed to examine which lesion locations result in disorganized visual search during cancellation tasks, in order to determine which brain areas are involved in search organization. A computerized shape cancellation task was administered in 78 stroke patients. As an index for search organization, the amount of intersections of paths between consecutive crossed targets was computed (i.e., intersections rate). This measure is known to accurately depict disorganized visual search in a stroke population. Ischemic lesions were delineated on CT or MRI images. Assumption-free voxel-based lesion-symptom mapping and region of interest-based analyses were used to determine the grey and white matter anatomical correlates of the intersections rate as a continuous measure. The right lateral occipital cortex, superior parietal lobule, postcentral gyrus, superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, inferior longitudinal fasciculus, first branch of the superior longitudinal fasciculus (SLF I), and the inferior fronto-occipital fasciculus, were related to search organization. To conclude, a clear right hemispheric dominance for search organization was revealed. Further, the correlates of disorganized search overlap with regions that have previously been associated with conjunctive search and spatial working memory. This suggests that disorganized visual search is caused by disturbed spatial processes, rather than deficits in high level executive function or planning, which would be expected to be more related to frontal regions. PMID- 26876011 TI - Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder. AB - Autism spectrum disorder (ASD) is an increasingly prevalent neurodevelopmental disorder characterized by deficits in sociability and communication, and restricted and/or repetitive motor behaviors. Amongst the diverse hypotheses regarding the pathophysiology of ASD, one possibility is that there is increased neuronal excitation, leading to alterations in sensory processing, functional integration and behavior. Meanwhile, the high-fat, low-carbohydrate ketogenic diet (KD), traditionally used in the treatment of medically intractable epilepsy, has already been shown to reduce autistic behaviors in both humans and in rodent models of ASD. While the mechanisms underlying these effects remain unclear, we hypothesized that this dietary approach might shift the balance of excitation and inhibition towards more normal levels of inhibition. Using high-resolution intracortical microstimulation, we investigated basal sensorimotor excitation/inhibition in the BTBR T+Itpr(tf)/J (BTBR) mouse model of ASD and tested whether the KD restores the balance of excitation/inhibition. We found that BTBR mice had lower movement thresholds and larger motor maps indicative of higher excitation/inhibition compared to C57BL/6J (B6) controls, and that the KD reversed both these abnormalities. Collectively, our results afford a greater understanding of cortical excitation/inhibition balance in ASD and may help expedite the development of therapeutic approaches aimed at improving functional outcomes in this disorder. PMID- 26876012 TI - Behavioral abnormalities in mice lacking mesenchyme-specific Pten. AB - Phosphatase and tensin homolog (Pten) is a negative regulator of cell proliferation and growth. Using a Cre-recombinase approach with Lox sequences flanking the fibroblast-specific protein 1 (Fsp1 aka S100A4; a mesenchymal marker), we probed sites of expression using a beta-galactosidase Rosa26(LoxP) reporter allele; the transgene driving deletion of Pten (exons 4-5) was found throughout the brain parenchyma and pituitary, suggesting that deletion of Pten in Fsp1-positive cells may influence behavior. Because CNS-specific deletion of Pten influences social and anxiety-like behaviors and S100A4 is expressed in astrocytes, we predicted that loss of Pten in Fsp1-expressing cells would result in deficits in social interaction and increased anxiety. We further predicted that environmental enrichment would compensate for genetic deficits in these behaviors. We conducted a battery of behavioral assays on Fsp1 Cre;Pten(LoxP/LoxP) male and female homozygous knockouts (Pten(-/-)) and compared their behavior to Pten(LoxP/LoxP) (Pten(+/+)) conspecifics. Despite extensive physical differences (including reduced hippocampal size) and deficits in sensorimotor function, Pten(-/-) mice behaved remarkably similar to control mice on nearly all behavioral tasks. These results suggest that the social and anxiety like phenotypes observed in CNS-specific Pten(-/-) mice may depend on neuronal Pten, as lack of Pten in Fsp1-expressing cells of the CNS had little effect on these behaviors. PMID- 26876013 TI - Microphthalmia-associated transcription factor regulates the visual cycle genes Rlbp1 and Rdh5 in the retinal pigment epithelium. AB - Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes, Rlbp1 which encodes retinaldehyde binding protein-1 (RLBP1), and Rdh5, which encodes retinol dehydrogenase-5 (RDH5). First, we found that Rlbp1 and Rdh5 are downregulated in optic cups and presumptive RPEs of Mitf-deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in Mitf-deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE. PMID- 26876014 TI - Outcomes in Stable Patients With Previous Atherothrombotic Events Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2 degrees P-TIMI 50). AB - Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for secondary prevention in stable patients with previous myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding and efficacy when started in that setting. The aim of this analysis was to investigate outcomes in patients who experienced a new ACS while receiving vorapaxar for long-term secondary prevention. Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic ischemic Events-Thrombolysis In Myocardial Infarction 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar (n = 26,449). We evaluated bleeding and ischemic events during the acute care of patients with a new ACS during the trial. During a median follow-up of 30 months, 799 patients (8.9%) randomized to vorapaxar and 913 (10.0%) to placebo had a new ACS event (p = 0.003); 87% and 86%, respectively, were on study therapy at the time of the event. In a landmark analysis through 7 days after ACS, the rates of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding were 0.8% versus 0.8% (hazard ratio [HR] 0.99, 95% CI 0.33 to 2.94) and GUSTO moderate/severe bleeding were 2.5% versus 1.6% (HR 1.59, 95% CI 0.78 to 3.24) with vorapaxar versus placebo. The effect of vorapaxar on cardiovascular death, MI, or stroke (2.4% vs 4.4%; HR 0.54, 95% CI 0.31 to 0.93; p = 0.027) was consistent with the overall trial result. In conclusion, in patients who experience a new ACS event while receiving vorapaxar for secondary prevention, continuing therapy was associated with favorable efficacy without excess severe bleeding during the period of acute ACS management. PMID- 26876015 TI - Bioaccessibility tests accurately estimate bioavailability of lead to quail. AB - Hazards of soil-borne lead (Pb) to wild birds may be more accurately quantified if the bioavailability of that Pb is known. To better understand the bioavailability of Pb to birds, the authors measured blood Pb concentrations in Japanese quail (Coturnix japonica) fed diets containing Pb-contaminated soils. Relative bioavailabilities were expressed by comparison with blood Pb concentrations in quail fed a Pb acetate reference diet. Diets containing soil from 5 Pb-contaminated Superfund sites had relative bioavailabilities from 33% to 63%, with a mean of approximately 50%. Treatment of 2 of the soils with phosphorus (P) significantly reduced the bioavailability of Pb. Bioaccessibility of Pb in the test soils was then measured in 6 in vitro tests and regressed on bioavailability: the relative bioavailability leaching procedure at pH 1.5, the same test conducted at pH 2.5, the Ohio State University in vitro gastrointestinal method, the urban soil bioaccessible lead test, the modified physiologically based extraction test, and the waterfowl physiologically based extraction test. All regressions had positive slopes. Based on criteria of slope and coefficient of determination, the relative bioavailability leaching procedure at pH 2.5 and Ohio State University in vitro gastrointestinal tests performed very well. Speciation by X-ray absorption spectroscopy demonstrated that, on average, most of the Pb in the sampled soils was sorbed to minerals (30%), bound to organic matter (24%), or present as Pb sulfate (18%). Additional Pb was associated with P (chloropyromorphite, hydroxypyromorphite, and tertiary Pb phosphate) and with Pb carbonates, leadhillite (a lead sulfate carbonate hydroxide), and Pb sulfide. The formation of chloropyromorphite reduced the bioavailability of Pb, and the amendment of Pb-contaminated soils with P may be a thermodynamically favored means to sequester Pb. Environ Toxicol Chem 2016;35:2311-2319. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. PMID- 26876016 TI - Jasmonate-responsive transcription factors regulating plant secondary metabolism. AB - Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. PMID- 26876018 TI - Point-of-Need bioanalytics based on planar optical interferometry. AB - This review brings about a comprehensive presentation of the research on interferometric transducers, which have emerged as extremely promising candidates for viable, truly-marketable solutions for PoN applications due to the attested performance that has reached down to 10(-8) in term of effective refractive index changes. The review explores the operation of the various interferometric architectures along with their design, fabrication, and analytical performance aspects. The issues of biosensor functionalization and immobilization of receptors are also addressed. As a conclusion, the comparison among them is attempted in order to delve into and acknowledge their current limitations, and define the future trends. PMID- 26876017 TI - Aptamer-based 'point-of-care testing'. AB - Aptamers are single-stranded oligonucleotides that can be artificially generated by a method called Systematic evolution of ligands by exponential enrichment (SELEX). The generated aptamers have been assessed for high-performance sensing applications due to their appealing characteristics. With either aptamers alone or complementing with antibodies, several high sensitive and portable sensors have been demonstrated for use in 'point-of-care testing'. Due to their high suitability and flexibility, aptamers are conjugated with nanostructures and utilized in field applications. Moreover, aptamers are more amenable to chemical modifications, making them capable of utilization with most developed sensors. In this overview, we discuss novel, portable, and aptamer-based sensing strategies that are suitable for 'point-of-care testing'. PMID- 26876019 TI - Fish oil diet modulates epididymal and inguinal adipocyte metabolism in mice. AB - We aimed to investigate the impact of different high-fat diets containing fish oil on adiposity and white adipose tissue (WAT) function in mice, comparing the effects on epididymal (eWAT) and subcutaneous (sWAT) depots. For this, we used C57BL/6 male mice fed four types of diets for eight weeks: standard chow (SC), high-fat lard (HF-L), high-fat lard plus fish oil (HF-L + FO), and high-fat fish oil (HF-FO). The HF-L group had a greater body mass (BM) gain, insulin resistance, increased gene expression related to lipogenesis (CD36, aP2, SREBP1c, and FAS), decreased gene expression of perilipin in both eWAT and sWAT, and reduced expression of genes related to beta-oxidation (CPT-1a) and to mitochondrial biogenesis (PGC1alpha, NRF1, and TFAM) in eWAT and sWAT. On the other hand, the HF-L + FO and HF-FO groups showed a smaller BM gain and adiposity, and normalization of insulin resistance and lipogenic genes in both eWAT and sWAT. These animals also showed decreased perilipin gene expression and elevated expression of beta-oxidation and mitochondrial biogenesis genes in eWAT and sWAT. 'Beige' adipocytes were identified in sWAT of the HF-FO animals. In conclusion, fish oil intake has anti-obesity effects through modulation of both eWAT and sWAT metabolism in mice and is relevant in diminishing the BM gain, adiposity, and insulin resistance even in combination with a high-fat lard diet in mice. PMID- 26876021 TI - Cleavage of fusion proteins on the affinity resins using the TEV protease variant. AB - It is documented that the tobacco etch virus protease (TEVp) variant TEVp3M is less efficient in cleaving the fusion protein bound to Ni-NTA resin at relatively low temperature. Here, we determined that, using the GFP fusion substrate bound to Ni-NTA or Strep-tactin agarose, activity of the TEVp5M variant was higher than that of the other TEVp construct, and about 15% higher than that of the TEVp3M. The GST fusion proteins immobilized on Strep-tactin agarose or Glutathione Sepharose were efficiently cleaved by purified TEVp5M at specified conditions using GFP reporter for visual track and detection. After on-column cleavage of three fusion constructs using the cognate TEVp5M constructs, two target proteins with relatively high purity were separated from Ni-NTA or Amylose agarose. With elution of the buffer containing 1 M NaCl, maize sulfiredoxin was released from Ni-NTA resin via on-column cleavage. Our results confirmed that TEVp5M efficiently cleaved the fusion proteins bound to the four affinity matrices. By combination with appropriate affinity handles, the cognate TEVp5M mediating tag removal enabled purification and cleavage of the fusion proteins, removal of the protease, and separation of the target proteins from the affinity resin to be accomplished in one step. PMID- 26876022 TI - Biomineral shell formation under ocean acidification: a shift from order to chaos. AB - Biomineral production in marine organisms employs transient phases of amorphous calcium carbonate (ACC) in the construction of crystalline shells. Increasing seawater pCO2 leads to ocean acidification (OA) with a reduction in oceanic carbonate concentration which could have a negative impact on shell formation and therefore survival. We demonstrate significant changes in the hydrated and dehydrated forms of ACC in the aragonite and calcite layers of Mytilus edulis shells cultured under acidification conditions (1000 MUatm pCO2) compared to present day conditions (380 MUatm pCO2). In OA conditions, Mytilus edulis has more ACC at crystalisation sites. Here, we use the high-spatial resolution of synchrotron X-ray Photo Emission Electron Microscopy (XPEEM) combined with X-ray Absorption Spectroscopy (XAS) to investigate the influence of OA on the ACC formation in the shells of adult Mytilus edulis. Electron Backscatter Diffraction (EBSD) confirms that OA reduces crystallographic control of shell formation. The results demonstrate that OA induces more ACC formation and less crystallographic control in mussels suggesting that ACC is used as a repair mechanism to combat shell damage under OA. However, the resultant reduced crystallographic control in mussels raises concerns for shell protective function under predation and changing environments. PMID- 26876024 TI - Editorial: New Drug Targets for Treatment of Recurrent/Metastatic Prostate Cancer. PMID- 26876023 TI - GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway. AB - Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis. GAME9 knockdown and overexpression in tomato and potato alters expression of SGAs and upstream mevalonate pathway genes including the cholesterol biosynthesis gene STEROL SIDE CHAIN REDUCTASE 2 (SSR2). Levels of SGAs, C24-alkylsterols and the upstream mevalonate and cholesterol pathways intermediates are modified in these plants. Delta(7)-STEROL-C5(6)-DESATURASE (C5 SD) in the hitherto unresolved cholesterol pathway is a direct target of GAME9. Transactivation and promoter-binding assays show that GAME9 exerts its activity either directly or cooperatively with the SlMYC2 transcription factor as in the case of the C5-SD gene promoter. Our findings provide insight into the regulation of SGA biosynthesis and means for manipulating these metabolites in crops. PMID- 26876025 TI - Side-gated ultrathin-channel nanopore FET sensors. AB - A side-gated, ultrathin-channel nanopore FET (SGNAFET) is proposed for fast and label-free DNA sequencing. The concept of the SGNAFET comprises the detection of changes in the channel current during DNA translocation through a nanopore and identifying the four types of nucleotides as a result of these changes. To achieve this goal, both p- and n-type SGNAFETs with a channel thicknesses of 2 or 4 nm were fabricated, and the stable transistor operation of both SGNAFETs in air, water, and a KCl buffer solution were confirmed. In addition, synchronized current changes were observed between the ionic current through the nanopore and the SGNAFET's drain current during DNA translocation through the nanopore. PMID- 26876026 TI - Fast Virtual Stenting with Active Contour Models in Intracranical Aneurysm. AB - Intracranial stents are becoming increasingly a useful option in the treatment of intracranial aneurysms (IAs). Image simulation of the releasing stent configuration together with computational fluid dynamics (CFD) simulation prior to intervention will help surgeons optimize intervention scheme. This paper proposed a fast virtual stenting of IAs based on active contour model (ACM) which was able to virtually release stents within any patient-specific shaped vessel and aneurysm models built on real medical image data. In this method, an initial stent mesh was generated along the centerline of the parent artery without the need for registration between the stent contour and the vessel. Additionally, the diameter of the initial stent volumetric mesh was set to the maximum inscribed sphere diameter of the parent artery to improve the stenting accuracy and save computational cost. At last, a novel criterion for terminating virtual stent expanding that was based on the collision detection of the axis aligned bounding boxes was applied, making the stent expansion free of edge effect. The experiment results of the virtual stenting and the corresponding CFD simulations exhibited the efficacy and accuracy of the ACM based method, which are valuable to intervention scheme selection and therapy plan confirmation. PMID- 26876027 TI - D-beta-aspartyl residue exhibiting uncommon high resistance to spontaneous peptide bond cleavage. AB - Although L-amino acids were selected as main constituents of peptides and proteins during chemical evolution, D-aspartyl (Asp) residue is found in a variety of living tissues. In particular, D-beta-Asp is thought to be stable than any other Asp isomers, and this could be a reason for gradual accumulation in abnormal proteins and peptides to modify their structures and functions. It is predicted that D-beta-Asp shows high resistance to biomolecular reactions. For instance, less reactivity of D-beta-Asp is expected to bond cleavage, although such information has not been provided yet. In this work, the spontaneous peptide bond cleavage was compared between Asp isomers, by applying real-time solution state NMR to eye lens alphaAlpha-crystallin 51-60 fragment, S(51)LFRTVLD(58)SG(60) and alphaBeta-crystallin 61-67 analog, F(61)D(62)TGLSG(67) consisting of L-alpha- and D-beta-Asp 58 and 62, respectively. Kinetic analysis showed how tough the uncommon D-beta-Asp residue was against the peptide bond cleavage as compared to natural L-alpha-Asp. Differences in pKa and conformation between L-alpha- and D-beta-Asp side chains were plausible factors to determine reactivity of Asp isomers. The present study, for the first time, provides a rationale to explain less reactivity of D-beta-Asp to allow abnormal accumulation. PMID- 26876036 TI - Brain structural changes in spasmodic dysphonia: A multimodal magnetic resonance imaging study. AB - INTRODUCTION: The pathophysiology of spasmodic dysphonia is poorly understood. This study evaluated patterns of cortical morphology, basal ganglia, and white matter microstructural alterations in patients with spasmodic dysphonia relative to healthy controls. METHODS: T1-weighted and diffusion tensor magnetic resonance imaging (MRI) scans were obtained from 13 spasmodic dysphonia patients and 30 controls. Tract-based spatial statistics was applied to compare diffusion tensor MRI indices (i.e., mean, radial and axial diffusivities, and fractional anisotropy) between groups on a voxel-by-voxel basis. Cortical measures were analyzed using surface-based morphometry. Basal ganglia were segmented on T1 weighted images, and volumes and diffusion tensor MRI metrics of nuclei were measured. RESULTS: Relative to controls, patients with spasmodic dysphonia showed increased cortical surface area of the primary somatosensory cortex bilaterally in a region consistent with the buccal sensory representation, as well as right primary motor cortex, left superior temporal, supramarginal and superior frontal gyri. A decreased cortical area was found in the rolandic operculum bilaterally, left superior/inferior parietal and lingual gyri, as well as in the right angular gyrus. Compared to controls, spasmodic dysphonia patients showed increased diffusivities and decreased fractional anisotropy of the corpus callosum and major white matter tracts, in the right hemisphere. Altered diffusion tensor MRI measures were found in the right caudate and putamen nuclei with no volumetric changes. CONCLUSIONS: Multi-level alterations in voice-controlling networks, that included regions devoted not only to sensorimotor integration, motor preparation and motor execution, but also processing of auditory and visual information during speech, might have a role in the pathophysiology of spasmodic dysphonia. PMID- 26876037 TI - Identifying clinical measures that most accurately reflect the progression of disability in Parkinson disease. AB - INTRODUCTION: The temporal relationship between disease and disability progression in Parkinson disease (PD) is not well understood. Our objective was to describe the natural, multidimensional trajectory of disability in persons with PD over a two-year period. METHODS: We conducted a multi-center, prospective cohort study involving four institutions. Data were collected at baseline and at 6-month intervals over 2 years using standardized clinical tests representing three World Health Organization defined disability domains: impairment, activity limitation, and participation restriction. Unadjusted mixed effects growth models characterized trajectories of disability in the three disability domains. The data set was analyzed using restricted maximum likelihood (REML) estimation. Standardized estimates of change were also computed using Cohen's d for each measure. RESULTS: Of the 266 enrolled participants, we analysed data from individuals who participated in at least 3 assessments (n = 207, 79%). Rates of disability progression over the 2-year period differed across domains. Moderate effects were detected for motor impairment (d = .28) and walking-related activity limitation (gait-related balance (d = .31); gait speed (d = .30)). Marginal effects were noted for upper extremity-related activity limitation (d = .11) and health-related quality of life participation restriction (d = .08). CONCLUSIONS: The natural trajectory of walking-related activity limitation was the most potent indicator of evolving disability, suggesting that routine assessment of walking and periodic rehabilitation is likely to be warranted for many persons with PD. Natural trajectories of disability provide important comparison data for future intervention studies. PMID- 26876038 TI - A novel pyrimidine tetrad contributing to stabilize tetramolecular G-quadruplex structures. AB - G-quadruplex structures formed by oligodeoxyribonucleotides TGGU(NH2)GGT (AM, U(NH2) = 5-amino-2'-deoxyuridine), TGGU(Br)GGT (BR, U(Br) = 5-bromo-2' deoxyuridine) and TGGTGGT (TH) have been investigated through circular dichroism, nuclear magnetic resonance, gel electrophoresis and molecular modeling techniques. Collected data indicate that all 7-mer oligonucleotides form tetramolecular parallel G-quadruplex structures with all residues adopting anti glycosidic bonds. In the case of AM, data suggest the occurrence of a novel U(NH2)-tetrad characterized by eight hydrogen bonds that stabilizes the G quadruplex structure more efficiently than U(Br)- and T-tetrads. PMID- 26876035 TI - 'Add, stir and reduce': Yersinia spp. as model bacteria for pathogen evolution. AB - Pathogenic species in the Yersinia genus have historically been targets for research aimed at understanding how bacteria evolve into mammalian pathogens. The advent of large-scale population genomic studies has greatly accelerated the progress in this field, and Yersinia pestis, Yersinia pseudotuberculosis and Yersinia enterocolitica have once again acted as model organisms to help shape our understanding of the evolutionary processes involved in pathogenesis. In this Review, we highlight the gene gain, gene loss and genome rearrangement events that have been identified by genomic studies in pathogenic Yersinia species, and we discuss how these findings are changing our understanding of pathogen evolution. Finally, as these traits are also found in the genomes of other species in the Enterobacteriaceae, we suggest that they provide a blueprint for the evolution of enteropathogenic bacteria. PMID- 26876034 TI - Synthetic biology to access and expand nature's chemical diversity. AB - Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology--including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits--and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products. PMID- 26876039 TI - Impact of Metal Nanoform Colloidal Solution on the Adaptive Potential of Plants. AB - Nanoparticles are a known cause of oxidative stress and so induce antistress action. The latter property was the purpose of our study. The effect of two concentrations (120 and 240 mg/l) of nanoform biogenic metal (Ag, Cu, Fe, Zn, Mn) colloidal solution on antioxidant enzymes, superoxide dismutase and catalase; the level of the factor of the antioxidant state; and the content of thiobarbituric acid reactive substances (TBARSs) of soybean plant in terms of field experience were studied. It was found that the oxidative processes developed a metal nanoparticle pre-sowing seed treatment variant at a concentration of 120 mg/l, as evidenced by the increase in the content of TBARS in photosynthetic tissues by 12 %. Pre-sowing treatment in a double concentration (240 mg/l) resulted in a decrease in oxidative processes (19 %), and pre-sowing treatment combined with vegetative treatment also contributed to the reduction of TBARS (10 %). Increased activity of superoxide dismutase (SOD) was observed in a variant by increasing the content of TBARS; SOD activity was at the control level in two other variants. Catalase activity decreased in all variants. The factor of antioxidant activity was highest (0.3) in a variant with nanoparticle double treatment (pre sowing and vegetative) at a concentration of 120 mg/l. Thus, the studied nanometal colloidal solution when used in small doses, in a certain time interval, can be considered as a low-level stress factor which according to hormesis principle promoted adaptive response reaction. PMID- 26876040 TI - Outdoor Temperature, Heart Rate and Blood Pressure in Chinese Adults: Effect Modification by Individual Characteristics. AB - We collected data from Kailuan cohort study from 2006 to 2011 to examine whether short-term effects of ambient temperature on heart rate (HR) and blood pressure (BP) are non-linear or linear, and their potential modifying factors. The HR, BP and individual information, including basic characteristics, life style, socio economic characteristics and other characteristics, were collected for each participant. Daily mean temperature and relative humidity were collected. A regression model was used to evaluate associations of temperature with HR and BP, with a non-linear function for temperature. We also stratified the analyses in different groups divided by individual characteristics. 47,591 residents were recruited. The relationships of temperature with HR and BP were "V" shaped with thresholds ranging from 22 degrees C to 28 degrees C. Both cold and hot effects were observed on HR and BP. The differences of effect estimates were observed among the strata of individual characteristics. The effect estimate of temperature was higher among older people. The cold effect estimate was higher among people with lower Body Mass Index. However, the differences of effect estimates among other groups were inconsistent. These findings suggest both cold and hot temperatures may have short-term impacts on HR and BP. The individual characteristics could modify these relationships. PMID- 26876041 TI - Serum matrix metalloproteinase 9 (MMP9) as a biochemical marker for wasting marmoset syndrome. AB - Use of the common marmoset (Callithrix jacchus) as a non-human primate experimental animal has increased in recent years. Although wasting marmoset syndrome (WMS) is one of the biggest problems in captive marmoset colonies, the molecular mechanisms, biochemical markers for accurate diagnosis and a reliable treatment remain unknown. In this study, as a first step to finding biochemical marker(s) for the accurate diagnosis of WMS, we conducted blood cell counts, including hematocrit, hemoglobin and platelets, and examined serum chemistry values, including albumin, calcium and levels of serum matrix metalloproteinase 9 (MMP9), using a colony of marmosets with and without weight loss. MMP9 is thought to be an enzyme responsible for the degradation of extracellular matrix components and participates in the pathogenesis of inflammatory conditions, such as human and murine inflammatory bowel disease, which, like WMS, are characterized histologically by inflammatory cell infiltrations in the intestines. The values of hematocrit and hemoglobin and levels of serum albumin and calcium in the WMS group were significantly decreased versus the control group. The platelet values and serum MMP9 concentrations were increased significantly in the WMS group compared with the control group. MMP9 could be a new and useful marker for the diagnosis of WMS in addition to hematocrit, hemoglobin, serum albumin and calcium. Our results also indicate that MMP9 could be a useful molecular candidate for treatment. PMID- 26876042 TI - Dopant-Free Hole-Transporting Material with a C3h Symmetrical Truxene Core for Highly Efficient Perovskite Solar Cells. AB - Herein we present a new structural design of hole-transporting material, Trux OMeTAD, which consists of a C3h Truxene-core with arylamine terminals and hexyl side-chains. This planar, rigid, and fully conjugated molecule exhibits excellent hole mobility and desired surface energy to the perovskite uplayer. Perovskite solar cells fabricated using the p-i-n architecture with Trux-OMeTAD as the p layer, show a high PCE of 18.6% with minimal hysteresis. PMID- 26876043 TI - Author's Response: Which cesarean scar defect should be treated; by which technique and by whom? PMID- 26876044 TI - Should Cesarean Scar Defect Be Treated Laparoscopically? A Case Report and Review of the Literature. PMID- 26876045 TI - Laparoscopic Gender Confirmation Surgery. PMID- 26876047 TI - Applying an ecological restoration approach to study patient safety culture in an intensive care unit. AB - AIMS AND OBJECTIVES: To gain an understanding of medication safety culture and other quality issues in a Brazilian intensive care unit using a restorative approach. BACKGROUND: Patient safety should be considered one of the pillars of quality in health care. Thus, patient safety culture is increasingly being explored as a guide for quality improvement efforts. DESIGN: A qualitative approach. METHODS: Participatory photographic research methods from the field of ecological restoration were adapted in this study. This study used focus groups, then subsequent nurse-led photo-narrated walkabouts, and photo elicitation with 23 nurses and one physician in interactive phases of data collection and analysis over an eight-month timeframe. RESULTS: The core themes identified were: the 'medication system shapes patient safety' and the 'feeling of helplessness in the face of the prevailing organization culture'. Participants discussed supports exiting in the intensive care unit that shape medication safety, the barriers that impede safe medication management, the solutions to improve medication safety and the creation of a better medication safety culture. CONCLUSIONS: The methods used allowed participants to visualise sound practices as well as key safety issues, reflect on their day-to-day work, re-think potential improvements, and enact changes to improve medication safety and medication safety culture. However, the patient safety culture is also marked by administrative pressure. The hospital needs to adopt participatory management, where the health professionals can act together with the organisational leaders to promote a just culture. RELEVANCE TO CLINICAL PRACTICE: The participatory photographic research methods from the field of ecological restoration provided participants with a tool to promote patient safety culture and engage policy change dialogue. However, it will be important in future restorative research to track-specific safety outcomes over time to assess the cost-benefit of the adoption of participatory management models. PMID- 26876046 TI - Protein Allostery and Conformational Dynamics. AB - The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond-nanosecond local and microsecond-millisecond conformational exchange dynamics, are presented. PMID- 26876049 TI - Atomic and electronic structure of twin growth defects in magnetite. AB - We report the existence of a stable twin defect in Fe3O4 thin films. By using aberration corrected scanning transmission electron microscopy and spectroscopy the atomic structure of the twin boundary has been determined. The boundary is confined to the (111) growth plane and it is non-stoichiometric due to a missing Fe octahedral plane. By first principles calculations we show that the local atomic structural configuration of the twin boundary does not change the nature of the superexchange interactions between the two Fe sublattices across the twin grain boundary. Besides decreasing the half-metallic band gap at the boundary the altered atomic stacking at the boundary does not change the overall ferromagnetic (FM) coupling between the grains. PMID- 26876048 TI - Transcriptional profiling of cortical versus cancellous bone from mechanically loaded murine tibiae reveals differential gene expression. AB - Mechanical loading is an anabolic stimulus that increases bone mass, and thus a promising method to counteract osteoporosis-related bone loss. The mechanism of this anabolism remains unclear, and needs to be established for both cortical and cancellous envelopes individually. We hypothesized that cortical and cancellous bone display different gene expression profiles at baseline and in response to mechanical loading. To test this hypothesis, the left tibiae of 10-week-old female C57Bl/6 mice were subjected to one session of axial tibial compression (9N, 1200cycles, 4Hz triangle waveform) and euthanized 3 and 24h following loading. The right limb served as the contralateral control. We performed RNA-seq on marrow-free metaphyseal samples from the cortical shell and the cancellous core to determine differential gene expression at baseline (control limb) and in response to load. Differential expression was verified with qPCR. Cortical and cancellous bone exhibited distinctly different transcriptional profiles basally and in response to mechanical loading. More genes were differentially expressed with loading at 24h with more genes downregulated at 24h than at 3h in both tissues. Enhanced Wnt signaling dominated the response in cortical bone at 3 and 24h, but in cancellous bone only at 3h. In cancellous bone at 24h many muscle related genes were downregulated. These findings reveal key differences between cortical and cancellous genetic regulation in response to mechanical loading. Future studies at different time points and multiple loading sessions will add to our knowledge of cortical and cancellous mechanotransduction with the potential to identify new targets for mouse genetic knockout studies and drugs to treat osteoporosis. PMID- 26876050 TI - Genetic association analysis of N-methyl-D-aspartate receptor subunit gene GRIN2B and clinical response to clozapine. AB - OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-D-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine. METHODS: GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment. Response was assessed using change in Brief Psychiatric Rating Scale scores following six months of clozapine therapy. Categorical and continuous response was assessed using chi-squared test and analysis of covariance, respectively. RESULTS: No associations were observed between the variants and response to clozapine. A-allele carriers of rs1072388 responded marginally better to clozapine therapy than GG-homozygotes; however, the difference was not statistically significant (p = 0.067, uncorrected). CONCLUSIONS: Our findings do not support a role for these GRIN2B variants in altering response to clozapine in our sample. Investigation of additional glutamate variants in clozapine response is warranted. PMID- 26876051 TI - Signatures of protein thermal denaturation and local hydrophobicity in domain specific hydration behavior: a comparative molecular dynamics study. AB - We investigate, using atomistic molecular dynamics simulations, the association of surface hydration accompanying local unfolding in the mesophilic protein Yfh1 under a series of thermal conditions spanning its cold and heat denaturation temperatures. The results are benchmarked against the thermally stable protein, Ubq, and behavior at the maximum stability temperature. Local unfolding in Yfh1, predominantly in the beta sheet regions, is in qualitative agreement with recent solution NMR studies; the corresponding Ubq unfolding is not observed. Interestingly, all domains, except for the beta sheet domains of Yfh1, show increased effective surface hydrophobicity with increase in temperature, as reflected by the density fluctuations of the hydration layer. Velocity autocorrelation functions (VACF) of oxygen atoms of water within the hydration layers and the corresponding vibrational density of states (VDOS) are used to characterize alteration in dynamical behavior accompanying the temperature dependent local unfolding. Enhanced caging effects accompanying transverse oscillations of the water molecules are found to occur with the increase in temperature preferentially for the beta sheet domains of Yfh1. Helical domains of both proteins exhibit similar trends in VDOS with changes in temperature. This work demonstrates the existence of key signatures of the local onset of protein thermal denaturation in solvent dynamical behavior. PMID- 26876052 TI - Hidradenocarcinoma presenting as soft tissue mass: Case report with cytomorphologic description, histologic correlation, and differential diagnosis. AB - Hidradenocarcinoma (HAC) is a rare adenexal tumor with a propensity for the head and neck region and extremities. We report a case of hidradenocarcinnoma in a 56 year-old woman with a mass on her right palm sampled by fine-needle aspiration and later confirmed on histological examination. Fine-needle aspiration cytology revealed a dual population of cells including polyhedral eosinophilic cells and glycogen containing cells with pale/clear cytoplasm. The nuclei were pleomorphic with prominent nucleoli. Occassional papillary structures were identified on the cell block material. A series of immunohistochemical stains were performed and an adnexal neoplasm was suggested. The mass was resected. On histologic sections, infiltration into the adjacent soft tissue was identified. After an additional series of immunohistochemical stains, the diagnosis was confirmed as a HAC. Herein, we present our findings and discuss the differential diagnoses. PMID- 26876053 TI - Shade of Resin-Based Luting Agents and Final Color of Porcelain Veneers. AB - OBJECTIVES: This study evaluated the influence of different shades of flowable resin composite used as luting agent on the final shade of porcelain veneers of different opacities over A2 and B1 simulated dental substrate. MATERIALS AND METHODS: One millimeter monolithic (enamel E1.0 or dentin D1.0) and bilayer (E0.5D0.5) porcelain discs shade A2 were paired with flowable resin composite disks (0.1 mm thick) of different shades (A1, A2, B1, white opaque - WO or IL - translucent), as veneer + luting agent (n = 10). The CIE L*a*b* color coordinates were measured with a spectrophotometer over white and black standard background, as well as over A2 and B1 simulated dental substrates. Translucency of all specimens and the shade matching of the pairs over the A2 and B1 substrates (DeltaE*00 ) were calculated by Translucency Parameter and CIEDE2000 methods. Data were statistically analyzed by 95% confidence interval. RESULTS: Porcelain veneer E1.0 groups were the most translucent, while the pairs veneer + luting agent WO showed the lowest translucency, and A1, A2, B1, and IL yielded little to no differences in translucency of the pairs. The overall best shade matching with A2 substrate was observed for D1.0 veneer + WO luting agent. CONCLUSION: The opacity of the porcelain veneer paired with luting agents of different shades affected the final appearance of the restorations over distinct simulated tooth substrates. CLINICAL SIGNIFICANCE: Distinct shades of flowable resin composites used as luting agent might yield clinically visible color differences on porcelain veneers facilitating an excellent shade match with adjacent teeth. (J Esthet Restor Dent 28:295-303, 2016). PMID- 26876054 TI - Synchronization of ovulation in cattle with an aromatase inhibitor-based protocol. AB - A study was designed to determine the effect of stage of the estrous cycle on the proportion of animals that ovulated and the synchrony of ovulation of heifers treated with an aromatase inhibitor-based protocol. Forty-eight heifers were treated intramuscularly with 500 MUg of cloprostenol (PGF) followed by 100 MUg of GnRH 24 hours later to serve as control data for comparison of the ovulatory response to a subsequent aromatase inhibitor protocol. Daily ultrasound examinations were done to determine the incidence of and interval to ovulation. At the time of ovulation (Day 0), heifers were assigned randomly to five day groups (n = 8-11/group) and given an intravaginal device containing 3 g of letrozole for 4 days starting on Day 0, 4, 8, 12, or 16. At the time of device removal, heifers were given PGF followed by GnRH 24 hours later. Ultrasound examinations were done daily from 2 days before device insertion to 9 days after the posttreatment ovulation. The preovulatory follicle diameter after letrozole treatment was larger in the Day 4 group compared to the Day 0 and 16 groups and intermediate in the Day 8 and 12 groups (P < 0.001). Compared to control data, the percentage of heifers that ovulated after letrozole treatment was greater (87.1% vs. 69.4%, respectively; P < 0.05) as was the synchrony of ovulation (residuals: 0.24 +/- 0.07 vs. 0.68 +/- 0.13; P < 0.01). The day on which letrozole treatment was initiated did not affect the proportion of heifers that ovulated or the interval to ovulation. Plasma estradiol concentrations at the time of removal of the letrozole device in the Day 0 and 4 groups was lower (P < 0.05) than in the corresponding controls. Estradiol concentrations in the Day 8 and 12 groups did not differ from already low concentrations in the respective controls. Corpus luteum diameter profiles and progesterone production were not affected by day-group although reduced luteal lifespan after letrozole treatment was observed and requires further investigation. In summary, a protocol involving a letrozole-impregnated intravaginal device for 4 days, PGF treatment at device removal, and GnRH 24 later resulted in a greater ovulation rate and greater synchrony of ovulation than in heifers not given letrozole. Results suggest that the protocol may be initiated effectively at random stages of the estrous cycle and may provide impetus for further studies to assess the efficacy of a letrozole based synchronization protocol for fixed-time insemination. PMID- 26876056 TI - Incorrect DFT-GGA predictions of the stability of non-stoichiometric/polar dielectric surfaces: the case of Cu2O(111). AB - Scanning tunneling microscopy (STM) and hybrid density functional theory (DFT) have been used to study the stability and electronic characteristics of the Cu2O(111) surface. We challenge previous interpretations of its structure and composition and show that only appropriate (hybrid) calculations can correctly account for the relative thermodynamic stability of stoichiometric versus Cu deficient terminations. Our theoretical finding of the stoichiometric surface to be most stable at oxygen-lean conditions is confirmed by an excellent matching between STM spectroscopy data and the calculated surface electronic structure. Beyond the specific case of the Cu2O(111) surface, and beyond the known deficiencies of GGA-based approaches in the description of oxide electronic structures, our work highlights the risk of an erroneous evaluation of the surface stability, in cases where the energetics and electronic characteristics are strongly coupled, as in a wide class of polar and/or non-stoichiometric oxide surfaces. PMID- 26876055 TI - Connexin 37 and 43 gene and protein expression and developmental competence of isolated ovine secondary follicles cultured in vitro after vitrification of ovarian tissue. AB - Cryoinjuries caused by vitrification of tissues and organs lead to the loss of membrane proteins that mediate intercellular communications, such as connexins 37 (Cx37) and 43 (Cx43). Thus, the present study aimed to evaluate ovine Cx37 and Cx43 gene and protein expressions and developmental competence by in vitro cultured secondary follicles retrieved from vitrified ovarian tissue. Ovarian fragments for the same ovary pair were distributed into six treatments: (1) fresh ovarian tissue (FOT); (2) vitrified ovarian tissue (VOT); (3) isolated follicles from fresh ovarian tissue (FIF); (4) isolated follicles from vitrified ovarian tissue; (5) isolated follicles from fresh ovarian tissue followed by in vitro culture (CFIF); (6) isolated follicles from vitrified ovarian tissue followed by in vitro culture (CVIF). In all treatments, Cx37 and Cx43 gene and protein expression patterns were evaluated by reverse transcription polymerase chain reaction and immunocytochemistry. In addition, secondary follicles were analyzed according to follicular integrity and growth, apoptosis, and cell proliferation. In vitro-cultured secondary follicles (CFIF and CVIF) were evaluated based on morphology (extruded follicles), antrum formation, and viability. The percentage of intact follicles was higher, whereas antrum formation, oocyte extrusion rate, and follicle viability were lower in CVIF than in CFIF treatment (P < 0.05). Terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphates nick end-labeling assay demonstrated that apoptosis was absent in FIF, whereas follicles from all other treatments showed positive labeling. Cell proliferation index was higher in isolated follicles from vitrified ovarian tissue and CVIF treatments than in follicles from FIF. Expression of Cx43 messenger RNA was lower in CVIF treatment when compared with follicles from all other treatments (P < 0.05). Follicle Cx37 messenger RNA levels did not show alterations in any treatment (P > 0.05). Cx37 and Cx43 immunolabeling was localized mainly on granulosa cells and oocytes, respectively. In conclusion, isolation of ovine secondary follicles could be done successfully after vitrification of ovarian tissue, and the basement membrane integrity remained intact after in vitro culture. Although the gene and protein expression of Cx37 did not change after vitrification of ovarian tissue, Cx43 turned out to be altered in secondary follicles after vitrification and in vitro culture. PMID- 26876057 TI - Mesalamine-induced myopericarditis - A case report. AB - Myopericarditis has occasionally been reported as a side effect of mesalamine in patients with inflammatory bowel disease. We present a 20-year-old woman with ulcerative colitis admitted with chest pain. After thorough investigation she was diagnosed with myopericarditis potentially related to mesalamine. There was complete clinical and laboratorial recovery following drug withdrawal. Although uncommon, the possibility of myopericarditis should be considered in patients with inflammatory bowel disease presenting with cardiac complaints. Early recognition can avoid potential life-threatening complications. PMID- 26876059 TI - Clinical features and laboratory findings of dengue fever in German travellers: A single-centre, retrospective analysis. AB - BACKGROUND: Dengue fever (DF) is one of the most relevant human arboviral infections worldwide and has become a frequent cause of fever in the returning traveller. This retrospective study aimed to characterize epidemiological and clinical features and laboratory findings of dengue fever in German travellers. METHODS: This descriptive study analyzed medical records of patients diagnosed with DF presenting at the Section of Tropical Medicine of the University Medical Centre Hamburg-Eppendorf from 2007 to 2011. Data were collected and analyzed retrospectively. RESULTS: In total, data of 119 DF patients (52 female, 67 male) were included in this study. The median age of the patients was 35 (range 15-75 years). DF was most frequently acquired in South-East Asia (n = 65; 54.7%), and in particular in Thailand (n = 23; 19.7%). A considerable percentage of DF infections (n = 14; 11.8%) was imported from Africa. Patients predominantly presented with fever, headache, rash, myalgia and arthralgia but also with gastrointestinal symptoms, i.e. diarrhoea. Nine patients showed signs of minor haemorrhagic manifestations. Neurological complications occurred in 13 patients. Low platelet count, leukopenia and elevated liver enzymes were the most relevant laboratory findings. Twenty patients (17.8%) had to be hospitalized. Overall, the clinical course was mostly mild to moderate, 13 patients (10.9%) showed DF warnings signs, no fatalities occurred. CONCLUSIONS: DF presented as a mostly mild to moderate disease in this study cohort. Outpatient treatment was adequate for the majority of patients. Still, detailed knowledge of clinical symptoms and laboratory features is essential for appropriate triage. PMID- 26876058 TI - Early determinants of food liking among 5y-old children: a longitudinal study from the EDEN mother-child cohort. AB - BACKGROUND: Identifying the determinants of child's liking for different foods may help to prevent future choices of unhealthy food. OBJECTIVE: To study early life food-related characteristics associated with child's liking for different foods at 5y with a longitudinal study. DESIGN: 1142 5y- old children completed a liking test for "fruit and vegetables", "meat, fish and eggs", desserts and cheese. Data related to maternal food intake before pregnancy, infant feeding during the first year of life, maternal feeding practices at 2y, child's food intake at 3y, and child's food neophobia from 1 to 4y were collected prospectively from the mother. The associations between these factors and child's liking for each category of foods were analyzed using structural equation modelling. RESULTS: High food neophobia at 4 y was related to lower child's liking for all food groups. Maternal feeding practices at 2y were associated with liking for dessert: negatively for the practices allowing child to control his/her own food intake, positively for restriction of child's food intake for weight reasons. Moreover, child's food intake at 3y was positively associated with child's liking for "fruit and vegetables" as well as for cheese. Finally, adherence to the infant feeding pattern "long breastfeeding, later introduction of main meal components and use of home-made products" was positively associated with child's liking for meat/fish/eggs. CONCLUSIONS: For all food groups, food neophobia was a common determinant of child's liking for food at 5y, whereas other factors were associated with food liking for specific food groups. PMID- 26876060 TI - Preventing mosquito bites--Websites and apps how well do we manage the advice? PMID- 26876061 TI - Zika without symptoms in returning travellers: What are the implications? AB - Against the background of the emergence and rapid spread of Zika virus (ZIKV) in the Americas, we report the case of an afebrile ZIKV infection in a traveller returning from Central America to highlight relevant clinical and diagnostic aspects. ZIKV should be considered in the differential diagnosis of patients with clinical symptoms suggestive of dengue or chikungunya fever. Given the frequent subfebril and afebrile manifestations of ZIKV infections, we propose abstaining from the term "Zika fever (ZF)" in favour of "Zika virus disease (ZVD)". Owing to its unspecific clinical presentation and cross-reactivity in serological assays, ZVD may easily be missed or misdiagnosed as dengue fever. Until conclusive data on the currently suspected link between ZIKV infection in pregnancy and foetal microcephaly become available, pregnant women and women who are trying to become pregnant should be advised against travelling to regions with ongoing ZIKV transmission. In addition, male travellers returning from regions with ongoing transmission should be informed of the potential risk of sexual transmission until conclusive data on the significance of this mode of transmission become available. Although probably low and seasonally restricted, there is a risk of ZIKV importation to Aedes mosquito-infested regions in temperate climates (including regions of North America and Europe) with consecutive autochthonous transmission. PMID- 26876062 TI - Multiple endocrine neoplasia type 2 kindred with novel tandem RET mutations: Case report with an applied in silico mutational tolerance analysis. AB - BACKGROUND: The American Thyroid Association (ATA) has established guidelines for prophylactic thyroidectomy in multiple endocrine neoplasia type 2A (MEN2A) based on rearranged during transfection (RET) mutations. In silico analysis, which uses computer modeling to predict alterations in protein structure, is a new method for studying these mutations. METHODS: We describe a kindred with MEN2A, all sharing a well-documented RET mutation, p.C634Y, as well as a mutation of undetermined significance, p.I852M, which we analyzed via in silico analysis. RESULTS: The p.C634Y mutation resulted in severe predicted RET alterations, whereas the p.I852M resulted in only modest changes. Both mutations together resulted in only a small additional disruptive effect in protein structure beyond that which occurred with p.C634Y alone. CONCLUSION: Although in silico analysis may be helpful in quantitating changes in protein structure that occur in patients who have novel RET mutations (single or multiple), additional factors must account for the highly variable aggressiveness of the disease (C-cell hyperplasia/medullary thyroid carcinoma [MTC]) noted in our kindred. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1881-E1885, 2016. PMID- 26876063 TI - Ethylhexylglycerin: a low-risk, but highly relevant, sensitizer in 'hypo allergenic' cosmetics. AB - BACKGROUND: Ethylhexylglycerin is a relatively new cosmetic ingredient that is used for its surfactant, emollient, skin-conditioning and antimicrobial properties. Since 2002, it has been occasionally reported as a contact allergen. OBJECTIVES: To report on 13 patients who presented with allergic contact dermatitis caused by ethylhexylglycerin, evaluated at two Belgian university patch test clinics during the period 1990-2015. PATIENTS AND METHODS: The patients were patch tested with the European baseline series, a cosmetic series, and - if indicated - additional series. Both the cosmetic products used and their single ingredients were patch tested. RESULTS: All but one of the ethylhexylglycerin-allergic patients were female, with a median age of 43 years (range: 29-81 years), most often suffering from dermatitis on the face, and sometimes on the hands and/or axillae. As the culprit products, leave-on cosmetics were identified, including a high number of proclaimed 'hypo allergenic' and 'preservative-free' facial creams, sun protection creams, and deodorants. CONCLUSIONS: Ethylhexylglycerin is a rare, but highly relevant, cosmetic sensitizer, even in those products advertised to be safe for consumers. Targeted patch testing with ethylhexylglycerin 5% pet. is very useful, and routine patch testing in a cosmetic series may be considered. Higher test concentrations might be indicated in selected cases. PMID- 26876064 TI - Should we wait until severe pulmonary hypertension develops? Efficacy of percutaneous mitral balloon valvuloplasty in patients with severe pulmonary hypertension: A subgroup analysis of our experience. AB - BACKGROUND: The primary goal of this study is to evaluate the immediate and long term ef-fects of percutaneous mitral balloon valvuloplasty (PBMV) on patients with rheumatic mitral stenosis (MS) complicated with severe pulmonary hypertension (PH). METHODS: The study population consisted of 85 patients with MS complicated with severe PH (systolic pulmonary pressure > 75 mm Hg). PBMV was performed with Inoue balloon technique. Clinical and echocardiographic follow-up was scheduled at 6 months and 1 year and yearly thereafter. RESULTS: Mitral valve area (MVA) was increased (pre-PBMV MVA was 1.03 +/- 0.21 cm2, post-PBMV MVA 1.89 +/- 0.34 cm2, p < 0.001) significantly. The mean and the maximum transmitral pressure gradient significantly decreased (pre-PBMV mean transmitral gradient was 18.47 +/- 6.59 mm Hg, post-PBMV 6.84 +/- 3.84 mm Hg, p < 0.001, pre-PBMV maximum transmitral pressure gradient was 27.6 +/- 8.38 mm Hg, post-PBMV 12.68 +/- 4.74 mm Hg, p < 0.001). Systolic pulmonary artery pressure (SPAP) significantly decreased (pre-PBMV 89.9 +/- 23.38 mm Hg, post-PBMV 54.5 +/- 14.6 mm Hg, p < 0.001). Two patients underwent surgery due to rupture of anterior mitral leaflet. There was no peri-procedural mortality. The procedure time was 29.12 +/- 11.37 min. Follow-up duration was 108.2 +/- 31.4 months. One patient died due to heart failure. One patient underwent re-PBMV and 7 patients mitral valve replacement. At the last follow-up, MVA still remained high (1.52 +/- 0.34 cm2) and mean transmitral pressure gradient was low (9.2 +/- 5.7 mm Hg). SPAP was 56.5 +/- 20.8 mm Hg which was the same as after PBMV. CONCLUSIONS: PBMV in patients with MS with severe PH is an effective therapy with low procedure time. However, it is recommended to perform PBMV before developing severe PH. PMID- 26876065 TI - Incidence of prosthesis-patient mismatch in patients receiving mitral Biocor(r) porcine prosthetic valves. AB - BACKGROUND: The aim was to assess the incidence of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) in patients receiving Biocor(r) porcine or mechanical valves, and to evaluate the effect of PPM on long-term survival. METHODS: All patients undergoing MVR between 2009 and 2013 received either mechanical or bioprosthetic valves (Biocor(r) porcine). PPM was defined as severe when the indexed effective ori-fice area was < 0.9 cm2/m2, moderate between 0.9 cm2/m2 and 1.2 cm2/m2 or absent > 1.2 cm2/m2. The primary endpoint was all-cause long-term mortality. RESULTS: Among a total of 136 MVR, PPM was severe in 27%, moderate in 44% and absent in 29% of patients. Implanted valves were 57% mechanical and 43% bioprosthetic. Only 3% of patients with mechanical valves had severe PPM vs. 59% with bioprostheses (p < 0.0001). Sixty-month survival with severe mismatch was 0.559 (SE 0.149) and with no mismatch 0.895 (SE 0.058) (p = 0.043). Survival of patients suffering from severe mismatch, or moderate mismatch with pulmonary hypertension (PH) was 0.749 (SE 0.101); while for patients with no mismatch or with moderate mismatch without PH, survival was 0.951 (SE 0.028) (p = 0.016). CONCLUSIONS: About one-fourth of patients had severe PPM and almost all of them had received a bioprosthesis. Sixty-month survival was significantly lower in patients with severe mismatch, or moderate mismatch with PH. Specifically, when a bioprothesis is chosen and while further evidence on the impact of PPM on clinical outcomes appears, surgeons are recommended to follow a preoperative strategy to implant a mitral prosthesis of adequate size in order to prevent PPM. PMID- 26876067 TI - Clinical manifestations and molecular mechanisms in the changing paradigm of vivax malaria in India. AB - BACKGROUND: Plasmodium vivax once considered benign is now being increasingly associated with complicated malaria where the spectrum of complications is vast and like Plasmodium falciparum. The clinical data is important with respect to the immunopathological status of the patient. Several genes like the vir genes and pvcrt-o are speculated to be attributing to the severity of P. vivax malaria. METHODS: In the present study we carried out the transcription analysis of five vir genes (vir 14-related, vir 12, vir 17-like, putative vir 14 and vir 10 related) and pvcrt-o gene in severe (n=12) and non-severe (n=7) P. vivax clinical infections and studied the correlation of these genes with clinical disease severity. RESULTS: This study revealed multiorgan involvement in severe vivax cases with severe thrombocytopenia and anemia, the predominantly occurring symptoms. Four out of five vir genes and pvcrt-o showed a significant increase in expression levels of severe infections compared to the non-severe infections indicating their possible role in the changing pathogenesis of P. vivax. CONCLUSIONS: The increased virulence in vivax malaria seems to be the result of multifactorial parameters changing it phenotypically as well as genotypically. However more studies are needed to understand the still nascent severity of P. vivax malaria. PMID- 26876066 TI - The effect of hemodynamically-guided hypotensive therapy in one-year observation: Randomized, prospective and controlled trial (FINEPATH study). AB - BACKGROUND: The use of impedance cardiography (ICG) revealed to provide beneficial blood pressure (BP) lowering effect. However, the follow-up in previous trials was short and brachial BP was the only evaluated hemodynamic variable. Thus, we aimed to estimate the influence of ICG-guided therapy on brachial and central BP, impedance-derived hemodynamic profile and echocardiographic features after 12 months in a randomized, prospective and controlled trial (NCT01996085). METHODS: One hundred and forty-four hypertensives were randomly assigned to groups of empiric (GE) and ICG-guided therapy (HD). Office BP, ambulatory BP monitoring, central BP and echocardiography (left ventricular hypertrophy and diastolic function assessment) were performed before and after 12 months of treatment. RESULTS: Blood pressure reduction was higher in HD (office BP: 21.8/14.1 vs. 19.9/11.8 mm Hg; mean 24-h BP: 19.0/10.9 vs. 14.4/9.2 mm Hg). However, the only statistically significant differences were: percentage of patients achieving BP reduction of minimum 20 mm Hg for of-fice diastolic BP (27.3% vs. 12.1%; p = 0.034) and mean 24-h systolic BP (49.1% vs. 27.3%; p = 0.013). More pronounced improvement in the left ventricular diastolic dysfunction (delta E/A 0.34 vs. 0.12, p = 0.017) was the only other beneficial hemodynamic effect. CONCLUSIONS: Beneficial BP lowering effect of hemodynamically guided pharmacotherapy, observed previously in short-term observation, persists over time. Hemodynamic effects of such a treatment approach, especially those of prognostic value (central BP, myocardial hypertrophy), should be evaluated in further studies including patients with resistant hypertension, heart failure, diabetes mellitus and chronic kidney disease. PMID- 26876068 TI - Establishing the Feasibility of Face Transplantation in Granulomatosis With Polyangiitis. AB - Granulomatosis with polyangiitis (GPA; formerly Wegener's granulomatosis) is a rare vasculitis that commonly starts in the craniofacial region. We report a case that was masked by prior facial trauma and associated with pyoderma gangrenosum (PG). Disease progression and aggressive debridements led to severe facial tissue loss. The decision to perform a face transplant was controversial because of the risk of disease relapse on the facial allograft. We reviewed renal transplant outcomes in GPA for possible relevance. A PubMed search retrieved 29 studies. Patient and graft survival, relapse, morbidity, mortality, rejection and immunosuppression were assessed. Ten-year patient survival and graft survival were 84.4% and 72.6%, respectively. GPA relapse occurred in 31.5%, and upper airway/ocular relapse occurred in 17.8% (resolved in 76.9%). Mortality was 12.3%. Acute and chronic rejection rates were 14.9% and 6.8%, respectively. Traditional posttransplant immunosuppression was effective. Our review suggests that GPA renal transplant outcomes are comparable to general renal transplant cohorts. Furthermore, transplanted GPA patients exhibit lower disease relapse secondary to lifelong immunosuppression. This supported our decision to perform a face transplant in this patient, which has been successful up to the present time (1 year posttransplantation). Untreated GPA and PG are potential causes of worse surgical outcomes in the craniofacial region. PMID- 26876069 TI - Time for hand-sewn anastomosis again? Comments on risk factors for anastomotic leak and postoperative morbidity and mortality after elective right colectomy for cancer: results from a prospective, multicentric study of 1102 patients. PMID- 26876071 TI - [Interpretation and consideration of the Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities management of asymptomatic disease and claudication]. AB - Atherosclerotic occlusive disease of the lower extremities (ASO-LE) has the third highest rate among systematic atherosclerosis obliterans, ranking after coronary heart disease and stoke, and the disease burden of ASO-LE has been continuously increasing. Invasive revascularizations, which is presented by endovascular therapy technique, has undergone a dramatic development in the past couples of decades. However, controversy concerned about the surgical management and operative indications has heated up in the meanwhile. Thus Society for Vascular Surgery (SVS) published the practice guidelines for ASO-LE with asymptomatic disease and claudication in March, 2015. At the first time the guideline definitely opposed the aggressive invasive revascularization for ASO-LE patients with asymptomatic disease or claudication under satisfied tolerance. Instead, it posed the extreme emphasis on the pharmacotherapy with risk reduction of atherosclerosis at the core and the exercise therapy with supervised or home based exercise program at the core for ASO-LE patients with asymptomatic disease and claudication. PMID- 26876070 TI - Skeletal muscle mass and quality as risk factors for postoperative outcome after open colon resection for cancer. AB - BACKGROUND: The prevalence of colorectal cancer in the elderly is increasing and, therefore, surgical interventions with a risk of potential complications are more frequently performed. This study investigated the role of low skeletal muscle mass (sarcopenia), muscle quality, and the sarcopenic obesity as prognostic factors for postoperative complications and survival in patients with resectable colon cancer. METHODS: We conducted a retrospective chart review of 91 consecutive patients who underwent an elective open colon resection for cancer with primary anastomosis between 2011 and 2013. Skeletal muscle mass was measured as total psoas area (TPA) and total abdominal muscle area (TAMA) at three anatomical levels on the preoperative CT scan. Skeletal muscle quality was measured using corresponding mean Hounsfield units (HU) for TAMA. Their relation with complications (none vs one or more), severe complications, and survival was analyzed. RESULTS: The study included 91 patients with a mean age of 71.2 +/- 9.7 years. Complications were noted in 55 patients (60 %), of which 15 (16.4 %) were severe. Lower HU for TAMA, as an indicator for impaired skeletal muscle quality, was an independent risk factor for one or more complications (all P <= 0.002), while sarcopenic obesity (TPA) was an independent risk factor for severe complications (all P <= 0.008). Sarcopenia was an independent predictor of worse overall survival (HR 8.54; 95 % confidence interval (CI) 1.07-68.32). CONCLUSION: Skeletal muscle quality is a predictor for overall complications, whereas sarcopenic obesity is a predictor for severe postoperative complications after open colon resection for cancer. Sarcopenia on itself is a predictor for worse overall survival. PMID- 26876072 TI - [Early experience of laparoscopic pancreaticoduodenectomy on 66 cases]. AB - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic pancreaticoduodenectomy(LPD). METHODS: Data of 66 patients from Sir Run Run Shaw Hospital undergoing LPD from September 2012 to September 2014 were reviewed. There were 44 male and 22 female with the mean age of (58.7+/-10.3) years and mean body mass index of (23.5+/-3.9)kg/m(2). Forty-five patients presented the symptoms and four of all had the history of abdominal surgery, including 2 cases of laparoscopic pancreatic surgery. RESULTS: Of 66 patients underwent laparoscopic procedure, 1 patient underwent LPD combined with right hepatic resection, 1 patient underwent laparoscopic distal gastrectomy with LPD, and 1 patient underwent LPD after laparoscopic distal pancreatectomy. The mean operative time was (367+/-49) minutes. The mean blood loss was(193+/-126)ml. The rate of overall postoperative complications was 36.4%(24/66), with 4.5%(3/66) of B or C pancreatic fistula and 7.6% (5/66) of bleeding. The mean postoperative hospital stay was (18.9+/-12.1) days. Mean tumor size was (3.8+/-2.3) cm, and the mean number of lymph nodes harvested was (20.3+/-10.9). Forty-severn patients were diagnosed as pancreatic adenocarcinoma(n=18), cholangiocarcinoma(n=7), ampullary adenocarcinoma(n=21), and gastric cancer(n=1), respectively. CONCLUSION: LPD is feasible and safe under the skilled hand. PMID- 26876073 TI - [Analysis of prognostic factors in patients with hepatocellular carcinoma (<=5 cm) underwent hepatectomy]. AB - OBJECTIVE: To explore the clinical and pathological factors influencing the prognosis of patients with hepatocellular carcinoma (HCC)(<=5 cm) after hepatectomy. METHODS: Two hundreds and nineteen cases with HCC(<=5 cm) undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 and July 2013 were collected. The alpha fetoprotein (AFP) level, tumor number, tumor size (diameter), liver cirrhosis, vascular invasion, capsular invasion, differentiation, surgical methods, resection margin, the way of treatments, the situation of recurrence and time to recurrence were analyzed. Log rank test and the stepwise Cox proportional-hazards models were used to compare the prognosis, respectively. RESULTS: The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3% respectively in all patients.Single factor analysis indicated that vascular invasion, capsular invasion, tumor size, hepatic vascular occult, liver cirrhosis, tumor differentiation, AFP, the way of treatments, the situation of recurrence and time to recurrence can affect the prognosis significantly (all P<0.05). The multifactor analysis showed that AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence were independent prognostic factors (all P<0.05). CONCLUSION: The prognosis of patients with HCC(<=5 cm) underwent hepatectomy are affected by multi-factors, such as AFP, tumor differentiation, liver cirrhosis, capsular invasion, tumor size and the situation of recurrence and time to recurrence. PMID- 26876074 TI - [Predictive factors of pathological complete response in primary human epidermal growth factor receptor 2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy]. AB - OBJECTIVE: To investigate the predictive factors of pathological complete response (pCR) in primary human epidermal growth factor receptor 2 (HER2) positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). METHODS: Totally 101 patients of primary HER2-positive breast cancer treated with trastuzumab-based NAC and subsequent curative surgical therapy in the Breast Disease Center of Peking University First Hospital from September 2007 to December 2014 were retrospectively reviewed. All patients were female with a median age of 53 (range 23 to 70) years.All patients received a taxanes- and carboplatin-containing chemotherapy, and trastuzumab was administered concurrently.A pCR, defined as the absence of invasive tumor cells in the breast and axillary lymph nodes, was achieved in 37.6% of patients (38/101). For analysis of the associations between clinicopathological factors and pCR, the chi(2) test or Fisher's exact test was used for univariate analysis, and multivariate Logistic regression analysis was performed to estimate OR and 95% CI. RESULTS: Tumor-infiltrating lymphocytes (chi(2)=14.981, P=0.000), hormone receptor (HR) status (chi(2)=9.513, P=0.002), and tumor grade (chi(2)=4.005, P=0.045) were significantly associated with pCR in univariate analysis. Tumor infiltrating lymphocytes positive (OR=4.74, 95% CI: 1.87 to 12.01, P=0.001) and HR-negative (OR=3.28, 95% CI: 1.31 to 8.20, P=0.011) were independent predictive factors of pCR in multivariate analysis. CONCLUSION: Tumor-infiltrating lymphocytes-positive and HR-negative were independent predictive factors of pCR in primary HER2-positive breast cancer treated with trastuzumab-based NAC. PMID- 26876075 TI - [Endovascular treatment of popliteal artery aneurysm in a clinical analysis of 9 cases]. AB - OBJECTIVE: To evaluate the efficacy of endovascular repair of popliteal artery aneurysm (PAA) and to summarize the clinical experience and lessons. METHODS: A clinical data of 9 PAA cases (males 8, females 1, age range 55-84) undergoing endovascular repair from October 2006 to December 2014 at Zhongshan Hospital Fudan University were retrospectively analyzed. CT angiography was made in all of the 9 cases preoperatively, and 10 PAA were included in the analysis. Of the 9 cases, 6 cases were symptomatic. The mean diameter of PAA was 3.9 cm (range, 2.1 8.2). RESULTS: The technique successful rate of endovascular repair was 10/10. The preoperative complications were 2/10, including one case suffered hematoma in the arterial puncture site and 1 case with distal artery embolization. The mean follow-up was 33 months (range, 3-87). During the follow-up, 2 cases received the secondary intervention and drug thrombolysis because of the stent distal thrombosis. The stent-graft primary patency at 1 year was 78.8% (95% CI: 48% 91%). One case suffered stent fracture, and one case died of brainstem hemorrhage 15 months post endovascular repair of PAA. CONCLUSIONS: Endovascular treatment of PAA is safe and effective in perioperative and midterm follow-up. However, individual endovascular strategy and postoperative complications in the long-term follow-up should be payed more attention. PMID- 26876076 TI - [An imaging study on effect of total artificial disc replacement on lumbar sagittal alignment]. AB - OBJECTIVE: To investigate effect of Activ L total lumbar disc replacement on lumbar sagittal alignment. METHODS: The imaging data of patients with degenerative disc disease received Activ L total lumbar disc replacement at Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University from March 2009 to March 2013 were retrospectively analyzed. The average age was 45.6 years(range, 35-60 years)and the surgery levels were as follows: L3-4 2 cases, L4-5 15 cases, L5/S1 5 cases, L3-4+ L4-5 3 cases, L4-5+ L5/S1 7 cases. All patients were followed up for 15 to 63 months(average, 32 months). Radiographic parameters such as lumbar lordosis angle(LL), segment lordosis angle(SL) and sacral slope angle(SS) were recorded. All the radiographic parameters were compared using one-way ANOVA at different stage. Lumbar lordosis angle of the two level was compared with the one of one-level by using independent sample t-test before and after the operation. A partial correction test was carried out to determine the corrections between the parameters preoperatively, one month after the operation and at final follow-up. RESULTS: One month after the operation, the lumbar lordosis angle decreased by an average of 1.8 degrees , but there was no statistically significant(P>0.05). Compared with one month postoperation, the lumbar lordosis angle increased by an average of 6.8 degrees (P<0.05), which also increased a lot compared with preoperation(P<0.05). The value of segment lordosis angle was rising up from preoperation to the final follow-up(P<0.05), so was the value of sacral slope angle, but there was no statistically significant between different stage(P>0.05). The lumbar lordosis angle showed no significant difference between double-level ones and single-level ones at different stage(P<0.05). The lumbar lordosis angle showed positive correlation with the sacral slope(P<0.001), however, the lumbar lordosis angle showed no corrected with the segment angle all the time(P>0.05). CONCLUSIONS: The total lumbar disc replacement with Activ L prosthesis had contributed to maintain and improve the lumbar alignment in the short and medium term. Double- or single-level total lumbar disc replacement had no significant effect on the value of lumbar lordosis angle. The lumbar lordosis angle showed positive correlation with the sacral slope all the time with no correlation between lumbar lordosis angle and sacral slope. PMID- 26876077 TI - [The efficacy and safety of postoperative retransfusion drain following total hip arthroplasty: a Meta-analysis]. AB - OBJECTIVE: To investigate the effectiveness and safety of post-operative retransfusion drain(PRD) after total hip arthroplasty. METHODS: A systematic literature review based on PubMed, EMBase, the Cochrane Library, China Biology Medicine disc, CNKI, VIP and WanFang Database in any language regarding PRD following total hip arthroplasty was performed.The data was evaluated using modified Jadad score and then analyzed using RevMan 5.2. RESULTS: Nine randomized controlled trials totaling 1 824 patients, 913 patients in PRD group and 911 in control group, were eligible for data extraction and Meta-analysis.The results indicated that the use of PRD could reduce the requirement of allogeneic blood transfusion when compared with ordinary vacuum drainage (RR=0.61, 95% CI= 0.47 0.79), but the benefit was not found when compared with no drainage group(RR=1.07, 95% CI=0.67-1.71). And the postoperative hemoglobin level was higher in PRD group(MD=0.14, 95% CI=0.01-0.27, P=0.04). No significant difference was identified regarding transfusion index, length of hospital stay, the incidence of febrile reaction and wound-related complications. CONCLUSIONS: PRD in reducing requirement of blood transfusion following THA is effective and safe when compared with ordinary vacuum drainage, but the benefit is not found when compared with no drainage.And more robust evidence is needed to confirm this result. PMID- 26876078 TI - [Diagnosis and treatment for intrathoracic gastroesophageal anastomotic leak: investigation of a new mode]. AB - OBJECTIVE: To investigate the feasibility of a new mode to diagnose and treat intrathoracic gastroesophageal anastomotic leak. METHODS: From January 2007 to December 2014, fifty-five patients were confirmed intrathoracic gastroesophageal anastomotic leak among those were performed surgical operation due to esophageal or cardiac carcinoma in the First Affiliated Hospital of Soochow University. To retrospectively analyze the clinical data of these patients, thirty-six male and nineteen female were included with the ages from 49 to 81 years (average age of (67+/-6)years). Among them, forty-two were middle esophageal carcinoma, eleven were lower esophageal carcinoma and two were cardiac carcinoma. According to the differences of diagnosis and treatment methods for anastomotic leak, fifty-five patients were divided into two groups. Thirty-one patients distributed from January 2007 to November 2011 were received conventional management (conventional group): to definitively diagnose by contrast swallow when suspected to be developing anastomotic leaks, to place an esophageal stent when the drainage was sufficient and the infection was controlled. Twenty-four patients distributed from March 2011 to December 2014 were received new-mode management (new-mode group): to perform a anastomotic radioscopy under digital subtraction angiography -guidance instantly when suspected anastomotic leak and find out the fistula, search the shape and size, place a drainage tube into the fistula to drain or lavage the vomica according to the exploration results, pull back the tube gradually and close the leak by clips under endoscope later. The pathoclinical features, the confirmation time (time from clinical signs emergence to leak confirmation), the hospital duration after confirmation, the incidence of severe complications and total mortality were compared between the two groups by t-test and chi(2) test or Fisher's exact test. RESULTS: There was no significant statistical differences in pathoclinical features between two groups (P>0.05). The confirmation time was significantly reduced in new-mode group than that in conventional group ((1.2+/-0.8) d vs. (3.6+/-2.2) d, t=5.212, P=0.000), and so was the hospital duration after confirmation ((26+/-12) d vs. (55+/-25) d, t=4.992, P=0.000) and the incidence of severe complications (16.7% vs. 48.4%, chi(2)=6.019, P=0.014), although there was no statistical differences in total mortality (4.2% vs. 22.6%, P=0.119). CONCLUSION: The new mode of early interventional diagnosis, early fistula drainage through nose and clipping under endoscope later is able to shorten diagnosis and treatment period, reduce incidence of severe complications. PMID- 26876079 TI - [Surgical outcomes of off-pump technique in extensive thoracoabdominal aorta replacement]. AB - OBJECTIVE: To assess the safety and efficacy of off-pump technique with normothemia to extend thoracoabdominal aortic aneurysm replacement compared with traditional hypothermic circulatory arrest. METHODS: From January 2004 to December 2013, 128 consecutive patients underwent surgical repair of thoracoabdominal aortic aneurysm (type Crawford II) in Fuwai Hospital. The mean age was (37+/-11) years. The patients included 74 cases (57.8%) with chronic Stanford A dissection, 34 cases (26.6%) with chronic Stanford B dissection, 20 cases (15.6%) with thoracoabdominal aortic true aneurysm. There were 71 patients who underwent hypothermic circulatory arrest surgery (cardiopulmonary bypass (CPB) group) and 57 patients who underwent off-pump surgery with normothermia (off-pump group). The clinic data was compared between the 2 groups using paired t tests and chi(2) test. Kaplan-Meier survival analysis was used for postoperative survival stays. RESULTS: The mean CPB time in CPB group was (251 +/ 87) minuets and the circulatory arrest time was (45+/-24) minuets. Spinal cord ischemia time in the two groups was (21+/-12) minuets and (18+/-10) minuets (t=5.68, P=0.51). The operation time, ventilator time, length of ICU stay and length of hospital stay of off-pump group were shorter than CPB group ((408+/ 114) minuets vs.(630+/-156) minuets, t=-7.67, P=0.05; (18+/-13) hours vs. (113+/ 89) hours, t=-3.86, P=0.00; (4+/-2) days vs.(10+/-9) days, t=-4.19, P=0.00; (15+/ 7) days vs.(25+/-14) days, t=-4.47, P=0.00). The intraoperative blood loss in off pump group and CPB group was (900+/-750) ml and (1 400+/-400) ml (t=-2.23, P=0.04). The mortality was 1.7% and 9.8% in the off-pump group and CPB groups (chi(2)=3.544, P=0.05). The cerebral complication rate in the normal temperature group was 1.7% vs. 22.6% in extracorporeal group (chi(2)=9.35, P<0.05). A total of 113 patients were followed up, with a follow-up rate of 88.2%. Duration of follow-up was (78+/-54) months. Five patients died during the follow-up period, including 2 who died of cerebral infarction and 3 paraplegia patients who died of infection. Eight patients had phase II aortic arch replacement after a mean time of 6 months. The overall postoperative survival rate was 97%, 93% and 87% at 3 years, 5 years and 7 years, respectively. CONCLUSION: Off-pump technique with normothemia was associated with a lower risk of a composite outcome of mortality and major adverse cardiac and cerebrovascular events during repair of extensive thoracoabdominal aortic aneurysm. PMID- 26876080 TI - [Intraoperative autologous based blood conservation strategies in mitral valve replacement]. AB - OBJECTIVE: To evaluate whether intraoperative autologous donation (IAD) can reduce perioperative blood transfusion for patients underwent mitral valve replacement (MVR). METHODS: A total of 318 patients received implementation of IAD from January 2011 to December 2013 were analyzed retrospectively, and compared with 517 patients of the previous 36-month period (from January 2008 to December 2012). The method of small-volume retrograde autologous priming, strict blood transfusion standard along with IAD together constituted a progressive blood-saving strategy. Statistical methods including Students' t-test, Pearson's chi(2) test, Kruskal-Wallis analysis and multivariate Logistic regression model were used for comparisons of the data. RESULTS: There were no significant difference between IAD group and non-IAD group considering preoperative patient demographics, characteristics and preoperative comorbidities. However, IAD group significantly reduced number of patients transfused with intra/post-operative packed red-blood cell (PRBC) (55(17.0%) vs. 215 (42.1%), chi(2)=53.0, P=0.000), and had significantly reduced postoperative chest tube output (150(380) ml vs. 700(660) ml, H=195.648, P=0.000), length of stay ((16+/-6) d vs. (20+/-8)d, t=9.60, P=0.000). But hematocrit were lower in IAD group (30%+/-5% vs.33%+/-4% at end of operation, t=7.76, P=0.000; 30%+/-4% vs. 32%+/-5% at discharge, P=0.000, t=3.86). Multivariate logistic aggression analysis revealed that age, IAD and smoking history were factors influencing the probability of intra or postoperative blood transfusion. CONCLUSION: Implementation of blood conservation strategies based on intraoperative autologous donation in mitral valve replacement surgery can significantly reduce intra/postoperative blood transfusion as well as postoperative complications. PMID- 26876081 TI - [A clinical observation of cool-tip radiofrequency ablation assisted enucleation for giant renal angiomyolipoma]. AB - OBJECTIVE: To initially explore the clinical effect of cool-tip radiofrequency ablation combined with enucleation for the giant hamartoma of kidney with narrow base and export-oriented way of growth. METHODS: The clinical date of 15 patients including 6 male and 9 female with special hamartoma of kidney underwent cool-tip radiofrequency ablation assisted enucleation from July 2011 to October 2014 were reviewed.The median age was 49 years (ranging from 35 to 71 years). There were 6 cases with left renal tumor, 8 cases with right renal tumor and 1 case with solitary kidney tumor.All patients were confirmed by B ultrasound or CT scan, the mean diameter of hamartoma of kidney was 9.7 cm(8.5-12.7)cm, all tumors were located distant from the collecting system and presents with a special way of growth.The preoperative hemoglobin was (129+/-18)g/L, SCr was (92+/-41)MUmol/L, glomerular filtration rate (GFR) was (32+/-12)ml.min(-1).1.73 m(-2). RESULTS: Cool-tip radiofrequency ablation assisted enucleation was technically successful in all patients.The mean operative duration was (115+/-31)minutes, and the average intraoperative bleeding was (72+/-21)ml with no blooding transfusion.The postoperative hospital stay was(7+/-2)days, and the postoperative hemoglobin was(129+/-18)g/L, SCr (92+/-41)MUmol/L, GFR(30+/-15)ml.min(-1).1.73 m(-2). No statistic change of hemoglobin and SCr or glomerular filtration rate after operations(all P>0.05). Postoperative pathology showed that all cases were hamartoma of kidney.During a mean follow-up period of 19.5 months, none of them had local tumor recurrence or chronic renal insufficiency. CONCLUSIONS: Cool-tip radiofrequency ablation assisted enucleation is both safe and effective in the treatment of huge hamartoma of kidney with a narrow base and export-oriented way of growth. The short-term follow-up shows a satisfactory therapeutic effect. PMID- 26876082 TI - [Clinical diagnosis and treatment of adrenocortical adenoma in patients aged 60 years or above]. AB - OBJECTIVE: To investigate the clinical features of adrenocortical adenoma's diagnosis and treatment in patients aged 60 years or above. METHODS: A retrospective study was performed with a total of 249 patients aged 60 years or above who suffered from adrenocortical adenoma and treated in Peking Union Medical College Hospital from January 2004 to January 2014.The clinical features, treatments and prognosis of the 249 patients aged 60 years or above were compared with another 249 patients which were randomly selected during the same period aged from 30 to 50 years.t-test or chi(2) test was used to analyze the data between the two groups. RESULTS: Endocrine examinations were performed in all 249 patients aged 60 years or above.There were 144 patients diagnosed as non functional adrenocortical adenoma, 94 cases as aldosterone-producing adenoma and 11 cases as Cushing adenoma.For the patients aged 60 years or above, the rate of cardio-cerebral vascular incident in non-functional adrenocortical adenoma group was 26.4%(38/144), which was significantly lower than that of the aldosterone producing adenoma and Cushing adenoma group(54.3%, 57/105)(chi(2)=20.027, P=0.000). There were 91.5%(65/71) of the patients aged 60 years or above who got a relief in low blood potassium symptoms after the operation.Forty-nine point one percent(53/108) of the non-functional adrenocortical adenoma patients aged 60 years or above had a better control of their blood pressure level, while functional adrenocortical adenoma group were 64.0%(48/75) which indicated that the functional adrenocortical adenoma patients have a better control of their blood pressure then the non-functional adrenocortical adenoma patients after the operation(chi(2)=3.987, P=0.046). There were 37.1% of the patients aged 60 years or above whose fasting blood-glucose was higher than 7.1 mmol/L, while the patients aged from 30 to 50 years was 14.1%(chi(2)=22.02, P=0.000). The differences in plasma aldosterone and blood potassium between the patients aged 60 years or above and the patients aged from 30 to 50 years had statistical significance(t=10.48, -2.58; P=0.00, 0.01). CONCLUSIONS: Most of the adrenocortical adenoma in patients aged 60 years or above is non-functional adrenocortical adenoma.Among who, patients with aldosterone-producing adenoma tend to have lower plasma aldosterone concentration and higher blood potassium level then the patients aged from 30 to 50 years.The patients aged 60 years or above with functional adrenocortical adenoma are tend to have severe cardio cerebral vascular incidence.A few of non-functional adrenocortical adenoma patients who combine with hypertension can benefit for the operation. PMID- 26876083 TI - [Efficacy of thromboelastography to monitor the clinical massive transfusion in scoliosis: a randomized controlled trial]. AB - OBJECTIVE: To systematically assess the benefits and harms of a thromboela stogram (TEG) guided transfusion strategy with severe bleeding. METHODS: In this prospective study, 60 patients scheduled for scoliosis were included in the Fourth Affiliated Hospital, Xinjiang Medical University, from May 2014 to February 2014.Patients were allocated into either an TEG group or a standard management group. RESULTS: There was no significant difference in age, weight, height and operation time between the two groups (P>0.05). There were significant differences in red blood cell concentration((4.5+/-1.5)units and(7.1+/ 1.2)units)(t=4.343, P=0.001), platelet((2.5+/-1.3)units and (4.2+/ 0.6)units)(t=4.554, P=0.002), fresh frozen plasma((234+/-46)ml and(514+/ 41)ml)(t=3.723, P=0.004), fibrinogen((2.4+/-0.6)g and (4.6+/-0.7)g)(t=3.451, P=0.006) between the TEG group and the standard management group.The two groups in intraoperative blood loss((1 023+/-103)ml and (1 314+/-116)ml)(t=2.260, P=0.120), incidence of rebleeding after operation(3.1% and 3.6%)(chi(2)=0.340, P=0.450), hospitalization time((18+/-4)d and (16+/-6)d)(t=2.140, P=0.160) had no statistically significant differences. CONCLUSION: Application of a TEG guided transfusion strategy seems to reduce the amount of bleeding during correction operation of scoliosis. PMID- 26876084 TI - [Progress in surgical treatment of hepatocellular carcinoma]. AB - The surgical treatment of hepatocellular carcinoma have advanced greatly in recent years: associating liver partition and portal vein ligation for staged hepatectomy can bring hope and relief to patients with advanced liver cancer and less future liver remnant; the application range of laparoscopic hepatectomy and robotic hepatectomy were amplified; hepatectomy following anatomic or non anatomic direction should be decided by particular situations; the precise preoperative assessment of liver reserve function ensured the success of extended hepatectomy; the further discussion of United Network for Organ Sharing criteria for liver transplantation made the appearance of University of California at San Francisco, Up-to-seven and Hangzhou criteria; bridge therapy can decrease tumor progression and the dropout rate from the liver transplantation waiting list; downstaging treatment is used in selected patients with more advanced liver cancer who are beyond the accepted transplant criteria to acquire the chance of liver transplantation and increase survival rates. PMID- 26876085 TI - [Reevaluation of transperineal prostate biopsy]. AB - In these recent over twenty years, transrectal prostate biopsy takes predominant place in diagnosing prostate cancer for its relatively convenient procedure and low cost. In contrast, transperineal biopsy approach is much less popular. However, transrectal prostate biopsy has disadvantages of"blind region"in the anterior apex regions of the prostate gland and relatively high risk of biopsy associated sepsis. The transperineal biopsy approach is again gaining attention and even becoming a mainstream approach. The advantages of transperineal prostate biopsy are the following: a high positive rate, particularly in the detection of tumors at the anterior or apical prostate; accurate assessment of the volume and Gleason score of prostate cancer; the possibility of providing information about the spatial distribution of the cancer; good consistency of pathology with radical resection; and a lower infection rate, making it suitable for patients with a high infection risks. The expansion of transperineal biopsy has been propagated by the increase in multiparametric MRI-guided biopsies, which often use the transperineal approach. PMID- 26876086 TI - [Progress of clinical application of functional MRI in the localization of brain language area]. AB - For surgical operation in the functional area in the brain, it's commonly demanded to resect the lesion to the maximal extent on the basis of preserve the normal neural function, thus the precise localization of functional area is extremely important. As for the advantages of being widely available, easy to grasp and non-invasive, the functional MRI (fMRI) has come into wide use, while the application of language fMRI is still in the initial stage. It's important to choose appropriate fMRI task according to the individual condition of the subject, the commonly-adopted tasks include verb generation, picture naming, word recognition, word generation, etc. However, the effectiveness of using fMRI to localize language area is not totally satisfactory, adopting multiple task is an effective approach to improve the sensitivity of this technique. The application of resting state fMRI in the localization of language area and the further research of the role of fMRI in localizing the Chinese language area are the important future directions. PMID- 26876087 TI - Expression of IL-1 and IL-6 and their natural regulators in leukocytes of B-cell chronic lymphocytic leukaemia patients. AB - PURPOSE: The purpose of the study was the assessment of the expression of IL 1beta and IL-6, and the proteins regulating their biological activity, namely IL 1RII, IL-1Ra, as well as sIL-6Ralpha, sgp-130 in leukemic lymphocytes and autologous neutrophils of B-CLL patients. MATERIAL/METHODS: The study involved a group of B-cell chronic lymphocytic leukemia patients and healthy volunteer blood donors. The presence of chosen proteins and their natural regulators was confirmed by Western blot. RESULTS: Western blot analysis showed a decreased expression of IL-1beta and IL-6 in the leukocytes of B-CLL patients. Decreased expression of sIL-6Ralpha has been observed in lymphocytes, with a simultaneous increase of expression in PMNs. Lower expression of sgp-130 was found in B cells while its expression was elevated in the neutrophils of patients in early stages of the disease. CONCLUSIONS: The changes observed in the expression of IL-1 and IL-6 seem to exclude their immediate involvement in the progress of B-CLL. However, the presented changes in the expression of proteins regulating IL-1beta and IL-6 in PMNs indicate a potential role of early immune response cells also in advanced stages of the disease. PMID- 26876088 TI - Changes of glycosylation of IgG in rheumatoid arthritis patients treated with methotrexate. AB - PURPOSE: In patients with active rheumatoid arthritis (RA) decrease of galactosylation is correlated with disease activity. The aim of our study was to evaluate an effect of methotrexate therapy on glycosylation disturbances of IgG in RA patients. MATERIALS/METHODS: IgG glycosylation in 40 patients with active RA treated with methotrexate for 12 months prior to and after treatment were compared. The control group consisted of 20 healthy volunteers. IgG glycosylation was assessed using biotinylated lectins and immunosorbent ELISA assay. For galactose specificity Datura stramonium lectin (DSA), for sialic acid Sambucus nigra (SNA) and Maackia amurensis (MAA) and for fucose residue Areulia auranta (AAA) lectins were used. RESULTS: In RA-cases N-glycan galactosylation and sialylation of IgG before treatment were significantly lower than in healthy subjects (for DSA, MAA lectins p<0.001 and SNA p<0.05). Significant increase of IgG galactosylation and sialylation in RA patients after therapy (for DSA, MAA and SNA lectin p<0.05) was detected. Moreover the glycosylation disturbances of N glycan IgG were strongly associated with changes of disease activity based on disease activity score. For fucose residues significantly higher absorbency of AAA lectin in RA patients before treatment was observed compared to control subjects (p<0.05) and slightly, not significantly decreased after MTX therapy. CONCLUSIONS: Defect of galactosylation of IgG in RA patients is a useful marker of disease activity that may be used for the assessment of therapy effectiveness. The role of IgG fucosylation and sialylation in RA pathogenesis has still to be determined. PMID- 26876089 TI - Long-term follow up of ileal pouch anal anastomosis in a large cohort of pediatric and young adult patients with ulcerative colitis. AB - AIM: The study's aim is to determine long-term outcomes in a large cohort of pediatric and young adult patients who underwent proctocolectomy with ileal pouch anal anastomsis (IPAA) for ulcerative colitis (UC). METHODS: Patients diagnosed with UC in childhood or adolescence (age<=21years) who underwent IPAA in childhood, adolescence, or young adulthood between 1982 and 1997 were contacted to determine pouch history, complications, and quality of life. RESULTS: Data were obtained from 74 patients out of a previously reported cohort. Median age at diagnosis of UC was 15years and at surgery was 18years. Median follow-up was 20years. Complications during follow-up were pouchitis (45%), strictures (16%), fistulae (30%), obstruction (20%), and change of diagnosis to Crohn's (28%). Twenty-three percent reported no complications. Fourteen percent had pouch failure, with Crohn's and fistulae reported to be the most frequent complications. Seventy-nine percent reported being very satisfied at 20years follow-up. CONCLUSION: To our knowledge, this study represents the largest cohort with the longest follow-up of pediatric and young adult patients undergoing IPAA for UC. Change in diagnosis to Crohn's and development of fistulae are risk factors for pouch failure. Despite reported complications, IPAA remains an excellent option for pediatric patients with UC. PMID- 26876091 TI - Corrigendum. PMID- 26876090 TI - Optimizing fluid resuscitation in hypertrophic pyloric stenosis. AB - BACKGROUND: Hypertrophic pyloric stenosis (HPS) is the most common diagnosis requiring surgery in infants. Electrolytes are used as a marker of resuscitation for these patients prior to general anesthesia induction. Often multiple fluid boluses and electrolyte panels are needed, delaying operative intervention. We have attempted to predict the amount of IV fluid boluses needed for electrolyte correction based on initial values. METHODS: A single center retrospective review of all patients diagnosed with HPS from 2008 through 2014 was performed. Abnormal electrolytes were defined as chloride <100mmol/L, bicarbonate >=30mmol/L or potassium >5.2 or <3.1mmol/L. Patients with abnormal electrolytes were resuscitated with 20ml/kg saline boluses and continuous fluids at 1.5 times maintenance rate. RESULTS: During the study period 542 patients were identified with HPS. Of the 505 who were analyzed 202 patients had electrolyte abnormalities requiring IV fluid resuscitation above maintenance, and 303 patients had normal electrolytes at time of diagnosis. Weight on presentation was significantly lower in the patients with abnormal electrolytes (3.8 vs 4.1kg, p<0.01). Length of stay was significantly longer in the patients with electrolyte abnormalities, 2.6 vs 1.9days (p<0.01). Fluid given was higher over the entire hospital stay for patients with abnormal electrolytes (106 vs 91ml/kg/d, p<0.01). The number of electrolyte panels drawn was significantly higher in patients with initial electrolyte abnormalities, 2.8 vs 1.3 (p<0.01). Chloride was the most sensitive and specific indicator of the need for multiple saline boluses. Using an ROC curve, parameters of initial Cl(-)80mmol/L and the need for 3 or more boluses AUC was 0.71. Modifying the parameters to initial Cl(-) <=97mmol/L and 2 boluses AUC was 0.65. A patient with an initial Cl(-)85 will need three 20ml/kg boluses 73% (95% CI 52-88%) of the time. A patient with an initial Cl(-) <=97 will need two 20ml/kg boluses at a rate of 73% (95% CI 64-80%). CONCLUSION: Children with electrolyte abnormalities at time of diagnosis of HPS have a longer length of stay; require more fluid resuscitation and more lab draws. This study reveals high sensitivity and specificity of presenting chloride in determining the need for multiple boluses. We recommend the administration of two 20ml/kg saline boluses separated by an hour prior to rechecking labs in patients with initial Cl(-) value <=97mmol/L. If the presenting Cl(-) <85 three boluses of 20ml/kg of saline separated by an hour are recommended. If implemented these modifications have potential to save time by not delaying care for extraneous lab results and money in the form of fewer lab draws. PMID- 26876093 TI - Complex sentence profiles in children with Specific Language Impairment: Are they really atypical? AB - Children with Specific Language Impairment (SLI) have language difficulties of unknown origin. Syntactic profiles are atypical, with poor performance on non canonical structures, e.g. object relatives, suggesting a localized deficit. However, existing analyses using ANOVAs are problematic because they do not systematically address unequal variance, or fully model random effects. Consequently, a Generalised Linear Model (GLM) was used to analyze data from a Sentence Repetition (SR) task involving relative clauses. seventeen children with SLI (mean age 6;7), twenty-one Language Matched (LM) children (mean age 4;8), and seventeen Age Matched (AM) children (mean age 6;5) repeated 100 canonical and non canonical sentences. ANOVAs found a significant Group by Canonicity interaction for the SLI versus AM contrast only. However, the GLM found no significant interaction. Consequently, arguments for a localized deficit may depend on statistical methods which are prone to exaggerate profile differences. Nonetheless, a subgroup of SLI exhibited particularly severe structural language difficulties. PMID- 26876092 TI - Coral community response to bleaching on a highly disturbed reef. AB - While many studies of coral bleaching report on broad, regional scale responses, fewer examine variation in susceptibility among coral taxa and changes in community structure, before, during and after bleaching on individual reefs. Here we report in detail on the response to bleaching by a coral community on a highly disturbed reef site south of mainland Singapore before, during and after a major thermal anomaly in 2010. To estimate the capacity for resistance to thermal stress, we report on: a) overall bleaching severity during and after the event, b) differences in bleaching susceptibility among taxa during the event, and c) changes in coral community structure one year before and after bleaching. Approximately two thirds of colonies bleached, however, post-bleaching recovery was quite rapid and, importantly, coral taxa that are usually highly susceptible were relatively unaffected. Although total coral cover declined, there was no significant change in coral taxonomic community structure before and after bleaching. Several factors may have contributed to the overall high resistance of corals at this site including Symbiodinium affiliation, turbidity and heterotrophy. Our results suggest that, despite experiencing chronic anthropogenic disturbances, turbid shallow reef communities may be remarkably resilient to acute thermal stress. PMID- 26876094 TI - Physical health nurse consultant role to improve physical health in mental health services: A carer's perspective. AB - The physical health of people diagnosed with a mental illness is significantly poorer in comparison with the general population. Awareness of this health disparity is increasing; however, strategies to address the problem are limited. Carers play an important role in the physical health care of people with mental illness, particularly in facilitating navigation of and advocating in the health care system. A specialist physical health nurse consultant position has been suggested as a way to address the physical health care disparity and limited research available suggests that positive outcomes are possible. In the present study, a qualitative exploratory research project was undertaken, involving in depth interviews with people identifying as mental health carers. Two focus groups and one individual interview were conducted involving a total of 13 carers. The resulting data were analyzed thematically. Views and opinions about the proposed physical health nurse consultant (PHNC) position were sought during these interviews and are reported in this paper. Two main sub-themes were evident relating to characteristics of this role: reliability and consistency; and communication and support. Essentially carers expressed a need for support for themselves and consumers in addressing physical health concerns. Successful implementation of this position would require a consistent and reliable approach. Carers are significant stakeholders in the physical health of consumers of mental health services and their active involvement in identifying and tailoring services, including development of the physical health nurse consultant must be seen as a priority. PMID- 26876095 TI - Preface. PMID- 26876096 TI - Munc18-1 and the Syntaxin-1 N Terminus Regulate Open-Closed States in a t-SNARE Complex. AB - Neuronal exocytosis is mediated by SNARE proteins, which assemble into a highly stable four-helical bundle in a process that is not well understood. Here, electron paramagnetic resonance spectroscopy was used to examine how the t-SNAREs syntaxin and SNAP25 assemble in the presence and absence of the regulatory protein Munc18-1. Syntaxin and SNAP25 form a 2:1 complex, which is structurally heterogeneous and persists in the presence of excess SNAP25. Munc18-1 dissociates this 2:1 complex, but a 1:1 complex is retained where syntaxin is in a closed state. In the absence of an N-terminal fragment of syntaxin, Munc18-1 also stabilizes a 1:1 complex of sytaxin/SNAP25; however, syntaxin now samples an open state. These data demonstrate that the open-closed syntaxin equilibrium is shifted toward the open state when syntaxin and Munc18-1 are associated with SNAP25, and the results indicate that a syntaxin/SNAP25:Munc18-1 complex is a likely starting point for SNARE assembly. PMID- 26876097 TI - Structural Basis for the Unique Multivalent Readout of Unmodified H3 Tail by Arabidopsis ORC1b BAH-PHD Cassette. AB - DNA replication initiation relies on the formation of the origin recognition complex (ORC). The plant ORC subunit 1 (ORC1) protein possesses a conserved N terminal BAH domain with an embedded plant-specific PHD finger, whose function may be potentially regulated by an epigenetic mechanism. Here, we report structural and biochemical studies on the Arabidopsis thaliana ORC1b BAH-PHD cassette which specifically recognizes the unmodified H3 tail. The crystal structure of ORC1b BAH-PHD cassette in complex with an H3(1-15) peptide reveals a strict requirement for the unmodified state of R2, T3, and K4 on the H3 tail and a novel multivalent BAH and PHD readout mode for H3 peptide recognition. Such recognition may contribute to epigenetic regulation of the initiation of DNA replication. PMID- 26876098 TI - Reconstructing the TIR Side of the Myddosome: a Paradigm for TIR-TIR Interactions. AB - Members of the Toll-like receptor and interleukin-1 (IL-1) receptor families all signal via Toll/IL-1R (TIR) domain-driven assemblies with adaptors such as MyD88. We here combine the mammalian two-hybrid system MAPPIT and saturation mutagenesis to complement and extend crystallographic and nuclear magnetic resonance data, and reveal how TIR domains interact. We fully delineate the interaction sites on the MyD88 TIR domain for homo-oligomerization and for interaction with Mal and TLR4. Interactions between three sites drive MyD88 homo-oligomerization. The BB loop interacts with the alphaE-helix, explaining how BB-loop mimetics inhibit MyD88 signaling. The alphaC'-helix interacts symmetrically. The MyD88 TIR domains thus assemble into a left-handed helix, compatible with the Myddosome death domain crystal structure. This assembly explains activation of MyD88 by Mal and by an oncogenic mutation, and regulation by phosphorylation. These findings provide a paradigm for the interaction of mammalian TIR domains. PMID- 26876099 TI - Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins. AB - Polyubiquitination, a critical protein post-translational modification, signals for a diverse set of cellular events via the different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the E-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. We assembled di-ubiquitins (Ub2) comprising every lysine linkage and examined them biochemically and structurally. Of these, K27-Ub2 is unique as it is not cleaved by most deubiquitinases. As this remains the only structurally uncharacterized lysine linkage, we comprehensively examined the structures and dynamics of K27-Ub2 using nuclear magnetic resonance, small angle neutron scattering, and in silico ensemble modeling. Our structural data provide insights into the functional properties of K27-Ub2, in particular that K27-Ub2 may be specifically recognized by K48-selective receptor UBA2 domain from proteasomal shuttle protein hHR23a. Binding studies and mutagenesis confirmed this prediction, further highlighting structural/recognition versatility of polyubiquitins and the potential power of determining function from elucidation of conformational ensembles. PMID- 26876101 TI - Cardiac troponins--Translational biomarkers in cardiology: Theory and practice of cardiac troponin high-sensitivity assays. AB - Tn is a unique translational biomarker in cardiology whose potential has not been diminished in the new era of high sensitive assays. cTns can be valuable markers in cardiac diseases as well as in infectious diseases and respiratory diseases. Furthermore, the role of cTns is growing in the routine evaluation of cardioxicity and in determining the efficacy/safety ratio of novel cardioprotective strategies in clinical settings. cTns can detect myocardial injury not only in a wide spectrum of laboratory animals in experimental studies in vivo, but also in isolated heart models or cardiomyocytes in vitro. The crucial issue regarding the cross-species usage of cardiac troponin investigation remains the choice of cardiac troponin testing. This review summarizes the recent proteomic data on aminoacid sequences of cTnT and cTnI in various species, as well as selected analytical characteristics of human cardiac troponin high sensitivity assays. Due to the highly phylogenetically conserved structure of troponins, the same bioindicator can be investigated using the same method in both clinical and experimental cardiology, thus contributing to a better understanding of the pathogenesis of cardiac diseases as well as to increased effectiveness of troponin use in clinical practice. Measuring cardiac troponins using commercially available human high-sensitivity cardiac troponin tests with convenient antibodies selected on the basis of adequate proteomic knowledge can solve many issues which would otherwise be difficult to address in clinical settings for various ethical and practical reasons. Our survey could help elaborate the practical guidelines for optimizing the choice of cTns assay in cardiology. PMID- 26876100 TI - Selective Binding of AIRAPL Tandem UIMs to Lys48-Linked Tri-Ubiquitin Chains. AB - Lys48-linked ubiquitin chains act as the main targeting signals for protein degradation by the proteasome. Here we report selective binding of AIRAPL, a protein that associates with the proteasome upon exposure to arsenite, to Lys48 linked tri-ubiquitin chains. AIRAPL comprises two ubiquitin-interacting motifs in tandem (tUIMs) that are linked through a flexible inter-UIM region. In the complex crystal structure UIM1 binds the proximal ubiquitin, whereas UIM2 (the double-sided UIM) binds non-symmetrically to the middle and distal ubiquitin moieties on either side of the helix. Specificity of AIRAPL for Lys48-linked ubiquitin chains is determined by UIM2, and the flexible inter-UIM linker increases avidity by placing the two UIMs in an orientation that facilitates binding of the third ubiquitin to UIM1. Unlike middle and proximal ubiquitins, distal ubiquitin binds UIM2 through a novel surface, which leaves the Ile44 hydrophobic patch accessible for binding to the proteasomal ubiquitin receptors. PMID- 26876102 TI - Characterization of a Colletotrichum population causing anthracnose disease on Olive in northern Tunisia. AB - AIMS: To phenotypically, physiologically and molecularly characterize the causal agent of olive anthracnose in the northern Tunisia and to study its genetic variability and pathogenicity. METHODS AND RESULTS: A total of 43 isolates were obtained from symptomatic olives collected from four regions in northern Tunisia. A range of morphological and physiological characteristics was recorded; and a phylogenetic study, based on the sequence analysis of both internal transcribed spacers and TUB2 gene regions, was performed. Of the 43 isolates, 41 were identified as Colletotrichum acutatum s.s, and only two were affiliated to Colletotrichum gloeosporioides s.s. Two more representative Spanish isolates, included for comparison, were identified as Colletotrichum godetiae. Using six inter-simple-sequence-repeat markers, homogeneity between isolates from different locations and within the same species was recorded. In pathogenicity and virulence studies, C. gloeosporioides s.s was found to be less virulent, while the Spanish C. godetiae isolate was significantly more virulent than the Tunisian C. acutatum s.s. CONCLUSIONS: Olive anthracnose in the North of Tunisia is mainly caused by C. acutatum s.s species. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study of olive anthracnose in Tunisia, which combines both phenotypic and molecular approaches. Colletotrichum acutatum s.s group was recorded for the first time in the country as the causal agent of olive anthracnose. PMID- 26876103 TI - Growth trend of small uterine fibroids and human chorionic gonadotropin serum levels in early pregnancy: an observational study. AB - OBJECTIVE: To analyze the growth trend of small uterine fibroids during early pregnancy, evaluating the potential factors involved, with particular interest in hCG levels. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENT(S): Women who had an ultrasound diagnosis of small myomas (diameter, >=10 mm and <=50 mm) from January 2007 to December 2013, and who subsequently became pregnant within 1 year. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Three additional ultrasound examinations were performed during early pregnancy (7-8, 10-13, and 20-22 complete gestational weeks, respectively) and the modifications in diameter and volume of each uterine fibroid were recorded. A serial evaluation of hCG serum levels from 5-12 weeks was performed. RESULT(S): From the 109 women who fulfilled the study inclusion/exclusion criteria, a significant increase emerged, both for volume and diameter of the detected fibroids. Specifically, a median growth rate (GR) of 122% was observed during the interval of the first to the second ultrasound, whereas a median GR of 108% was detected during the interval between the second and the third ultrasound, and a median GR of 25% between the third and the fourth ultrasound. A significant positive correlation between hCG levels and diameter (R = 0.69) of myomas between 5 and 12 weeks emerged. CONCLUSION(S): A remarkable nonlinear growth of small fibroids during initial pregnancy was observed, with a faster rate in the first trimester and a slowdown by midpregnancy. Those changes seem to be related to the similar increase of hCG levels until 12 weeks. PMID- 26876104 TI - Long-acting follicle-stimulating hormone versus daily follicle-stimulating hormone for women undergoing assisted reproduction. AB - Follicle-stimulating hormone (FSH) given as a weekly injection in a medium dose is as safe and effective as a daily FSH injection for women undergoing assisted reproduction. PMID- 26876105 TI - Comparison of fluorescent tags for analysis of mannose-6-phosphate glycans. AB - Mannose-6-phosphate (M-6-P) glycan analysis is important for quality control of therapeutic enzymes for lysosomal storage diseases. Here, we found that the analysis of glycans containing two M-6-Ps was highly affected by the hydrophilicity of the elution solvent used in high-performance liquid chromatography (HPLC). In addition, the performances of three fluorescent tags--2 aminobenzoic acid (2-AA), 2-aminobenzamide (2-AB), and 3-(acetyl-amino)-6 aminoacridine (AA-Ac)--were compared with each other for M-6-P glycan analysis using HPLC and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The best performance for analyzing M-6-P glycans was shown by 2-AA labeling in both analyses. PMID- 26876106 TI - A transverse pull-through suture technique to repair volar plate avulsion for a chronic swan neck deformity. PMID- 26876107 TI - Poly Implant ProtheseTM (PIP) experience in the United Kingdom: A prospective cohort study into the accuracy of diagnostic imaging findings in comparison to operative findings of 1029 implants. PMID- 26876108 TI - Oncological outcomes of lipofilling breast reconstruction: 195 consecutive cases and literature review. AB - INTRODUCTION: Lipofilling has become a widely used procedure in breast reconstruction after mastectomy or breast-conserving treatment. The possibility that this technique may increase stimulation of cancer development between the potential tumor bed and the lipoaspirates grafts has been raised regarding its safety. The aim of this study was to identify the oncological risks associated with this procedure in our institution. METHODS: Between years 2007 and 2014 we record 195 consecutive patients with fat grafting technique for reconstructive purpose after breast cancer treatment. The loco-regional recurrence (LRR) as first event of relapse was the primary end point of this study. RESULTS: We performed 319 lipofilling procedures in 132 mastectomy and 63 breast-conserving surgery patients. Invasive carcinoma represents 81.6% of the series. The median follow-up from primary cancer surgery and fat grafting was 74 and 31 months respectively. Median time between oncologic surgery and lipofilling was 36 months. The authors observed a complication rate of 8.2%, most of them liponecrosis and oil cysts (7.2%). Four local, 2 regional and 4 distant recurrences were observed as first event of relapse in 10 patients with invasive ductal carcinoma. The loco-regional recurrence rate was 3.1% (1.08% per year). CONCLUSIONS: Although larger prospective trials are needed, these results support the fact that lipofilling following breast cancer treatment leads to a very low rate of complications and similar to other authors, it does not seem to interfere in patient's oncological prognosis when compared with prior publications. PMID- 26876109 TI - [A case of myasthenia gravis with transient taste disorders followed by aplastic anemia after thymectomy]. AB - A 45-year-old man was admitted to our hospital because of taste disorders in March 2014. He exhibited cervical muscle weakness and left eye ptosis, which responded to Tensilon test, and was diagnosed with myasthenia gravis (MG). He developed aspiration pneumonia and myasthenic crisis, which was treated with intravenous immunoglobulin and steroid pulse therapy. All symptoms disappeared. Oral administration of prednisolone and tacrolimus was started. Chest CT revealed thymoma and extended thymectomy was performed in May 2014. In December 2014, seven months after the thymectomy, hematological examination showed pancytopenia including severe neutropenia. We diagnosed his illness as aplastic anemia (AA). Cyclosporine therapy with transfusion was administerd and led to reticulocyte count recovery. Since May 2015, hemoglobin recovery reached a blood transfusion free period. To our knowledge, this is the first case report with the patient supposed of relationship among taste disorders, AA and thymoma-associated MG. PMID- 26876110 TI - [Diagnoses of corticobasal syndrome and corticobasal degeneration]. AB - Experts use the term corticobasal syndrome (CBS) for patients with a clinical diagnosis of corticobasal degeneration (CBD), and reserve CBD for those whose conditions have been diagnosed on the basis of neuropathological analyses. Several studies demonstrated that patients with CBD may also present with progressive supranuclear syndrome (PSPS), aphasia, Alzheimer disease-like dementia or behavioral change, suggesting that CBS is merely one of the presenting phenotypes of CBD. Although previous CBD diagnostic criteria reflected only CBS, the international consortium proposed new diagnostic criteria for CBD in 2013 (Armstrong's criteria). The new criteria include 4 CBD subtypes; CBS, frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA),and PSPS. These subtypes were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD (cr-CBD) and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies (p-CBD). Two studies have already revealed that the sensitivity and specificity of the criteria were not high. Because therapeutic interventions that target abnormally-phosphorylated tau have started, further refinement of the criteria is needed via biomarker researches with prospective study designs. PMID- 26876111 TI - Effect of adding amino acids residues in N- and C-terminus of Vip3Aa16 (L121I) toxin. AB - To study the importance of N- and C-terminus of Bacillus thuringiensis Vip3Aa16 (L121I) toxin (88 kDa), a number of mutants were generated. The addition of two (2R: RS) or eleven (11R: RSRPGHHHHHH) amino acid residues at the Vip3Aa16 (L121I) C-terminus allowed to an unappropriated folding illustrated by the abundant presence of the 62 kDa proteolytic form. The produced Vip3Aa16 (L121I) full length form was less detected when increasing the number of amino acids residues in the C-terminus. Bioassays demonstrated that the growth of the lepidopteran Ephestia kuehniella was slightly affected by Vip3Aa16 (L121I)-2R and not affected by Vip3Aa16 (L121I)-11R. Additionally, the fusion at the Vip3Aa16 (L121I) N terminus of 39 amino acids harboring the E. coli OmpA leader peptide and the His tag sequence allowed to the increase of protease sensitivity of Vip3Aa16 (L121I) full length form, as only the 62 kDa proteolysis form was detected. Remarkably, this fused protein produced in Escherichia coli (E. coli) was biologically inactive toward Ephestia kuehniella larvae. Thus, the N-terminus of the protein is required to the accomplishment of the insecticidal activity of Vip3 proteins. This report serves as guideline for the study of Vip3Aa16 (L121I) protein stability and activity. PMID- 26876112 TI - Burkitt's Lymphoma of the Rectosigmoid and Stomach Presenting as Hematochezia. AB - BACKGROUND: Burkitt's lymphoma (BL) is an uncommon cause of non-Hodgkin lymphoma in adults and accounts for only 0.1-0.5% of all malignant tumors of the colon and rectum. Very few cases of rectosigmoid and stomach BL have been reported in adults. CASE REPORT: A 51-year-old Hispanic woman presented with a 1-month history of hematochezia, associated with a foreign-body sensation in the rectum and 7 kg weight loss. Initial laboratory workup showed normocytic anemia and positive fecal occult blood. Computed tomography of the abdomen revealed an asymmetric appearance of the stomach and pylorus with nodularity of the mucosa and thickening of the posterior wall, and a 10.8-cm rectal mass. Esophagogastroduodenoscopy and colonoscopy were performed and biopsies of the stomach and rectum were obtained; histopathology demonstrated involvement by Burkitt's lymphoma in the gastric body nodule and rectal mass. After 4 cycles of chemotherapy, a follow-up abdominal CT demonstrated complete resolution of the mural thickening of the rectum and no intra-abdominal lymphadenopathy. CONCLUSIONS: Our case illustrates the importance of considering BL in the extensive differential diagnosis of rectal bleeding, change in bowel habits, and other lower and upper GI symptoms, since the rapidly growing nature of this rare malignancy requires a prompt diagnosis and initiation of appropriate therapy. PMID- 26876113 TI - The Role of Sequential Pneumatic Compression in Limb Salvage in Non reconstructable Critical Limb Ischemia. AB - OBJECTIVE: Critical limb ischemia (CLI) is an increasingly alarming presentation of advanced generalized circulatory failure. Most patients presenting with CLI have profound cardiovascular comorbidities that hinder surgical intervention. Moreover, some patients present with non-reconstructable arterial anatomy. For this vulnerable cohort, primary amputation is often the only available option. This study aims at answering the question: Can sequential pneumatic compression (SPC) preclude amputation? METHODS: A retrospective analysis of 187 patients (262 limbs) prescribed the Artassist SPC compared outcomes between the group of patients who acquired the device and those who did not. The primary end point was limb salvage; secondary end points were amputation-free survival and improvement in toe pressures. RESULTS: The mean age was 74.78 years, the median follow-up was 16 months, and the median duration of usage was 4 months. 81.72% of the patient acquired the device and 18.28% did not. The mean toe pressure was 61.4 mmHg pre application, and 65 mmHg after application (p = .071). Amputation-free survival was 98% and 96% for those who acquired the device and 90% and 84% for those who did not at 6 and 12 months, respectively. There was a non-significant association between limb salvage and device acquisition (p = .714); however, there was a significant improvement in rest pain (p < .0001), reduction in minor amputation (p = .023), and amputation-free survival associated with using the device (p = .01). CONCLUSIONS: Although limb salvage is the paramount ambition for patients referred to vascular services, some patients with CLI are better served with primary amputation. Although the mechanism of SPC action is still ambiguous, there is strong evidence to support its role in preventing minor amputation, prolonging amputation-free survival, and improving rest pain in patients with non reconstructable CLI; nevertheless, its role in prevention of major amputation lacks statistical significance. PMID- 26876114 TI - Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy. AB - Cerebral amyloid angiopathy (CAA) is a neurovascular disease that is strongly associated with an increase in the number and size of spontaneous microbleeds. Conventional methods of magnetic resonance imaging for detection of microbleeds, and positron emission tomography with Pittsburgh Compound B imaging for amyloid deposits, can separately demonstrate the presence of microbleeds and CAA in affected brains in vivo; however, there still is a critical need for strong evidence that shows involvement of CAA in microbleed formation. Here, we show in a Tg2576 mouse model of Alzheimer's disease, that the combination of histochemical staining and an optical clearing method called optical histology, enables simultaneous, co-registered three-dimensional visualization of cerebral microvasculature, microbleeds, and amyloid deposits. Our data suggest that microbleeds are localized within the brain regions affected by vascular amyloid deposits. All observed microhemorrhages (n=39) were in close proximity (0 to 144 MUm) with vessels affected by CAA. Our data suggest that the predominant type of CAA-related microbleed is associated with leaky or ruptured hemorrhagic microvasculature. The proposed methodological and instrumental approach will allow future study of the relationship between CAA and microbleeds during disease development and in response to treatment strategies. PMID- 26876115 TI - Microarterial anastomoses: A parameterised computational study examining the effect of suture position on intravascular blood flow. AB - This study investigates the extent to which individual aspects of suture placement influence local haemodynamics within microarterial anastomoses. An attempt to physically quantify flow characteristics of blood past microvascular sutures is made using computational fluid dynamics (CFD) software. Particular focus has been placed on increased shear strain rate (SSR), a known precipitant of intravascular platelet activation and thrombosis. Measurements were taken from micrographs of sutured anastomoses in chicken femoral vessels, with each assessed for bite width, suture angle and suture spacing. Computational geometries were then created to represent the anastomosis. Each suture characteristic was parameterised to allow independent or simultaneous adjustment. Flow rates were obtained from anonymised Doppler ultrasound scans of analogous vessels during preoperative assessment for autologous breast reconstruction. Vessel simulations were performed in 2.5mm ducts with blood as the working fluid. Vessel walls were non-compliant and a continuous Newtonian flow was applied, in accordance with current literature. Suture bite angle and spacing had significant effects on local haemodynamics, causing notably higher local SSRs, when simulated at extremes of surgical practice. A combined simulation, encompassing subtle changes of each suture parameter simultaneously i.e. representing optimum technique, created a more favourable SSR profile. As such, haemodynamic changes associated with optimum suture placement are unlikely to influence thrombus formation significantly. These findings support adherence to the basic principles of good microsurgical practice. PMID- 26876116 TI - Perceived stress, coping, and cortisol reactivity in daily life: A study of adolescents during the first year of college. AB - Adolescents change how they cope with stress across different situations, but also differ from one another in their general capacity to cope. The current study examined whether cortisol reactivity to perceived daily stress varies with both situational (within-person) and individual (between-person) differences in coping. First-year college students (N=63; Mage=18.85) provided 15 stress-coping diaries and 15 corresponding saliva samples across 3 weekdays. Results from hierarchical linear growth models revealed that perceiving greater stress than usual in the last hour was significantly associated with elevations in cortisol (relative to diurnal patterning) only during situations characterized by greater than usual diary-reported engagement coping. Regarding individual differences, perceiving greater stress than usual was significantly associated with elevations in cortisol only for adolescents below average on trait measures of engagement coping or belief in their ability to handle stress. Findings indicate that cortisol reactivity to daily stress varies with both situational variation and individual differences in coping. PMID- 26876117 TI - Dopamine D2 and serotonin 5-HT1A receptor interaction in the context of the effects of antipsychotics - in vitro studies. AB - The serotonin 5-HT1A receptor (5-HT1 A R) and dopamine D2 receptor (D2 R) have been implicated as important sites of action in antipsychotics. Several lines of evidence indicate the key role of G protein-coupled receptors (GPCRs) heteromers in pathophysiology of schizophrenia and highlight these complexes as novel drug targets. Because heterodimers can form only on those cells co-expressing constituent receptors, they present a target of high pharmacological specificity in the context of biochemical effects induced by antipsychotic drugs. In studies conducted in the HEK 293 cell line, we demonstrated that 5-HT1 A R and D2 R are able to form constitutive heterodimers, and antipsychotic drugs (clozapine, olanzapine, aripiprazole, and lurasidone) enhanced this process, with clozapine being most effective. Various functional tests (cAMP and IP1 as well as ERK activation) indicated that the drugs had different effects on signal transduction by the heteromer. Interestingly, co-incubation of heterodimer-expressing HEK 293 cells with clozapine and the 5-HT1 A R agonist 8-OH DPAT potentiated post synaptic effects, especially with respect to ERK activation. Our results indicate that the D2 -5-HT1A complex possesses biochemical, pharmacological, and functional properties distinct from those of mono- and homomers. This result has implications for the development of improved pharmacotherapy for schizophrenia or other disorders (activating the heteromer might be cognitive enhancing, since it is expressed in frontal cortex) through the specific targeting of heterodimers. We reported the constitutive formation of D2 -5-HT1A heteromers, which possess biochemical, pharmacological, and functional properties distinct from those of mono- and homomers, as revealed by antipsychotics action. We also showed that these two receptors are co-expressed in mouse cortical neurons; therefore their potential to heterodimerize may comprise an essential target for the development of novel strategies for schizophrenia treatment. PMID- 26876118 TI - Risk Assessment and Management of the Mother with Cardiovascular Disease. AB - Chronic medical conditions account for most nonobstetrical pregnancy-related maternal complications. Preconception counseling of women with cardiovascular disease can be aided by an understanding of cardiovascular physiology in pregnancy and risk scores to guide management. PMID- 26876119 TI - Fetal Diagnostics and Fetal Intervention. AB - Advances in ultrasound technology and specialized training have allowed clinicians to diagnose congenital heart disease in utero and counsel families on perinatal outcomes and management strategies, including fetal cardiac interventions and fetal surgery. This article gives a detailed approach to fetal cardiac assessment and provides the reader with accompanying figures and video clips to illustrate unique views and sweeps invaluable to diagnosing congenital heart disease. We demonstrate that using a sequential segmental approach to evaluate cardiac anatomy enables one to decipher the most complex forms of congenital heart disease. Also provided is a review of fetal cardiac intervention and surgery from the fetal cardiologist's perspective. PMID- 26876121 TI - Perinatal and Delivery Management of Infants with Congenital Heart Disease. AB - Advances in fetal echocardiography have improved prenatal diagnosis of congenital heart disease (CHD) and allowed better delivery and perinatal management. Some newborns with CHD require urgent intervention after delivery. In these cases, delivery close to a pediatric cardiac center may be considered, and the presence of a specialized cardiac team in the delivery room or urgent transport of the infant should be planned in advance. Delivery planning, monitoring in labor, rapid intervention at birth if needed, and avoidance of iatrogenic preterm delivery have the potential to improve outcomes for infants with prenatally diagnosed CHD. PMID- 26876120 TI - Genetic and Developmental Basis of Cardiovascular Malformations. AB - Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1% to 5% of all live births. Genetic, epigenetic, and environmental factors all influence the development of CVMs, and an improved understanding of the causation of CVMs is a prerequisite for prevention. Cardiac development is a complex, multistep process of morphogenesis that is under genetic regulation. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are still identified infrequently. This article discusses the key genetic concepts characterizing human CVMs, their developmental basis, and the critical developmental and genetic concepts underlying their pathogenesis. PMID- 26876122 TI - Screening for Critical Congenital Heart Disease. AB - Screening for critical congenital heart disease (CCHD) was added to the United States Recommended Uniform Screening Panel in 2011. Since that time, CCHD screening with pulse oximetry has become nearly universal for newborns born in the United States. There are various algorithms in use. Although the goal of the screening program is to identify children who may have CCHD, most newborns who have a low oxygen saturation will not have CCHD. Further study is needed to determine optimal guidelines for CCHD screening in special settings such as the neonatal intensive care unit, areas in high altitude, and home births. PMID- 26876123 TI - Recognition of Undiagnosed Neonatal Heart Disease. AB - Heart defects are the most common congenital malformation. Approximately 8000 infants per year in the United States require diagnosis in the newborn period to avoid severe injury or death. It is incumbent on the neonatologist and pediatrician to expeditiously detect the presence of symptomatic heart disease so that infants can be stabilized before cardiovascular decompensation. Evaluating infants and further categorizing them into the particular pathophysiology are necessary to stabilize them in anticipation of more definitive care by the pediatric cardiac team. PMID- 26876124 TI - Fetal and Neonatal Arrhythmias. AB - Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID- 26876125 TI - Recent Advances in the Treatment of Preterm Newborn Infants with Patent Ductus Arteriosus. AB - A patent ductus arteriosus (PDA) is associated with several adverse clinical conditions. Several strategies for PDA treatment exist, although data regarding the benefits of PDA treatment on outcomes are sparse. Moreover, the optimal treatment strategy for preterm neonates with PDA remains subject to debate. It is still unknown whether and when PDA treatment should be initiated and which approach (conservative, pharmacologic, or surgical) is best for individual patients (tailored therapies). This article reviews the current strategies for PDA treatment with a special focus on recent developments such as oral ibuprofen, high-dose regimens, and the use of paracetamol (oral, intravenous). PMID- 26876126 TI - Nutrition in the Cardiac Newborns: Evidence-based Nutrition Guidelines for Cardiac Newborns. AB - Both protein and energy malnutrition are common in neonates and infants with congenital heart disease (CHD). Neonates with CHD are at increased risk of developing necrotizing enterocolitis (NEC), particularly the preterm population. Mortality in patients with CHD and NEC is higher than for either disease process alone. Standardized feeding protocols may affect both incidence of NEC and growth failure in infants with CHD. The roles of human milk and probiotics have not yet been explored in this patient population. PMID- 26876127 TI - Developmental Care Rounds: An Interdisciplinary Approach to Support Developmentally Appropriate Care of Infants Born with Complex Congenital Heart Disease. AB - Newborn infants with complex congenital heart disease are at risk for developmental delay. Developmental care practices benefit prematurely born infants in neonatal intensive care units. Cardiac intensive care units until recently had not integrated developmental care practices into their care framework. Interdisciplinary developmental care rounds in our center have helped in the promotion of developmentally supportive care for infants before and after cardiac surgery. This article discusses basic principles of developmental care, the role of each member of the interdisciplinary team on rounds, common developmental care practices integrated into care from rounds, and impacts to patients, families, and staff. PMID- 26876128 TI - Management of the Preterm Infant with Congenital Heart Disease. AB - The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD. PMID- 26876129 TI - Neurodevelopmental Outcomes of the Child with Congenital Heart Disease. AB - Survival after bypass surgery in moderate and severe congenital heart disease (CHD) has increased dramatically. Although cardiac outcome is often very good, these children are at increased risk of developmental impairments in all developmental domains. Risk factors for developmental impairment include a genetic disorder, preterm birth, longer intensive care stay, poorer socioeconomic environment, and more complex forms of CHD. Health care providers, patients, and parents must be aware and informed about noncardiac sequelae and tertiary centers performing open-heart surgery in neonates and infants must establish a neurodevelopmental follow-up program to provide regular neurodevelopmental assessments. These allow for individual counseling and early detection and treatment of developmental problems. PMID- 26876130 TI - Pulmonary Hypertension and Pulmonary Vasodilators. AB - Pulmonary hypertension in the perinatal period can present acutely (persistent pulmonary hypertension of the newborn) or chronically. Clinical and echocardiographic diagnosis of acute pulmonary hypertension is well accepted but there are no broadly validated criteria for echocardiographic diagnosis of pulmonary hypertension later in the clinical course, although there are significant populations of infants with lung disease at risk for this diagnosis. Contributing cardiovascular comorbidities are common in infants with pulmonary hypertension and lung disease. It is not clear who should be treated without confirmation of pulmonary vascular disease by cardiac catheterization, with concurrent evaluation of any contributing cardiovascular comorbidities. PMID- 26876131 TI - The Journey to Adult Congenital Heart Disease. PMID- 26876132 TI - Perinatal Cardiovascular Disease. PMID- 26876133 TI - CDKN2A mutations with p14 loss predisposing to multiple nerve sheath tumours, melanoma, dysplastic naevi and internal malignancies: a case series and review of the literature. AB - An inherited germline mutation in CDKN2A is the most common cause of familial atypical multiple mole melanoma (FAMMM) syndrome. Although it is well known that CDKN2A mutations confer an increased risk for melanoma and pancreatic carcinoma, the association with an increased risk for nerve sheath tumours and other tumour types is under-recognized. We report a family with a missense mutation (c.151 1G>C) at the acceptor splice site of intron 1 of CDKN2A, resulting in loss of function of both tumour suppressor proteins p16(INK) (4) and p14(ARF) . This mutation is associated with a clinical phenotype of FAMMM syndrome in which patients develop numerous benign and malignant mutations, brain tumours, sarcomas and other solid tumours, in addition to melanoma and dysplastic naevi. Our proband initially presented with multiple nerve sheath tumours, leading to diagnostic confusion with Neurofibromatosis type 1. Loss of p14 expression results in increased MDM2-mediated degradation of the tumour suppressor protein p53, and predisposes mutation carriers to multiple benign and malignant neoplasms. This article highlights the importance of considering CDKN2A mutations in patients with dysplastic naevi, melanoma and multiple nerve sheath tumours, specifically those with histological features of both neurofibromas and schwannomas. We also present a discussion of medical management for patients with this high-risk cancer susceptibility syndrome. PMID- 26876134 TI - In vivo analysis of effects of venom from the jellyfish Chrysaora sp. in zebrafish (Danio rerio). AB - The jellyfishes of the genus Chrysaora are present in all of the world's oceans, but the toxicity of their venoms has not yet been thoroughly characterized. The zebrafish as a toxicology model can be used for general toxicity testing of drugs and the investigation of toxicological mechanisms. The aim of this study was to evaluate the effect of crude venom from jellyfish Chrysaora sp., a species of jellyfish observed in the tropical lagoons of the Gulf of Mexico, on the zebrafish Danio rerio. Juvenile zebrafish were injected with different concentrations of venom from Chrysaora sp. via intraperitoneal and subcutaneous injections. The effects of the venom were determined by histopathological analysis and through the measurement of hemolytic and phospholipase A2 activities. The crude venom was examined by SDS-PAGE. The effect of sublethal concentrations of crude venom from Chrysaora sp. on D. rerio was hemorrhaging in the eyes, while the histopathological analysis demonstrated that the primary organs targeted were the pseudobranch, which displayed hyperemia, and the gill, which displayed hyperplasia and hypertrophy. The blood analysis exhibited hemolysis, nuclear abnormalities, and echinocytes by the action of phospholipase A2, which was determined to have 596 units of activity/mg of protein in the venom. The crude venom has proteins with molecular weights ranging from 250 to 6 kDa, with more density in the bands corresponding to 70, 20 and 15 kDa. The venom of Chysaora sp. caused disturbances in circulation associated with vascular dilation due to the localized release of inflammatory mediators. The hemolysis of erythrocytes was caused by the action of phospholipase A2. These findings not only provide an excellent study model but also have a great pharmacological potential for designing new drugs and for the elucidation of the mechanisms of action of and treatment against stings. PMID- 26876135 TI - Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity. AB - The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 MUg, 0.1 MUg, and 0.2 MUg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content. PMID- 26876137 TI - Stereotypic behaviour in standard non-enriched cages is an alternative to depression-like responses in C57BL/6 mice. AB - Depressive-like forms of waking inactivity have been recently observed in laboratory primates and horses. We tested the hypotheses that being awake but motionless within the home-cage is a depression-like symptom in mice, and that in impoverished housing, it represents an alternative response to stereotypic behaviour. We raised C57BL/6 ('C57') and DBA/2 ('DBA') females to adulthood in non-enriched (n=62 mice) or enriched (n=60 mice) cages, observing home-cage behaviour during the active (dark) phases. We predicted that being still but awake would be reduced by environmental enrichment; more pronounced in C57s, as the strain most prone to learned helplessness; negatively related to stereotypic behaviour; and positively related to immobility in Forced Swim Tests (FST). Compared to enriched mice, non-enriched subjects did spend more time spent being inactive but awake, especially if they displayed relatively little stereotypic behaviour. C57 mice also spent more time awake but motionless than DBAs. Furthermore, even after statistically controlling for housing type and strain, this behaviour very strongly tended to predict increased immobility in the FST, while high levels of stereotypic behaviours in contrast predicted low immobility in the FST. Being awake but motionless is thus a reaction to non-enriched housing that seems to be an alternative to stereotypic behaviour, and could reflect depression-like states. PMID- 26876138 TI - Distinct state anxiety after predictable and unpredictable fear training in mice. AB - Sustained fear paradigms in rodents have been developed to monitor states of anxious apprehension and to model situations in patients suffering from long lasting anxiety disorders. A recent report describes a fear conditioning paradigm, allowing distinction between phasic and sustained states of conditioned fear in non-restrained mice. However, so far no prospective studies have yet been conducted to elucidate whether induction of phasic or sustained fear can affect states of anxiety. Here, we used CS (conditioned stimulus) and US (unconditioned stimulus) pairing with predictable and unpredictable timing to induce phasic and sustained fear in mice. State anxiety during various fear response components was assessed using the elevated plus-maze test. Training with unpredictable CS-US timing resulted in CS-evoked sustained components of fear (freezing), while predictable CS-US timing resulted in rapid decline. Data suggested the influence of training procedure on state anxiety which is dependent on progression of conditioned fear during fear memory retrieval. Animals trained with unpredictable CS-US timing showed an unchanged high anxiety state throughout behavioral observation. In contrast, mice trained with predictable CS-US timing showed anxiolytic-like behavior 3 min after CS onset, which was accompanied by a fast decline of the fear conditioned response (freezing). Further systematic studies are needed to validate the phasic/sustained fear model in rodents as translational model for anxiety disorders in humans. PMID- 26876136 TI - Adolescent social defeat alters N-methyl-D-aspartic acid receptor expression and impairs fear learning in adulthood. AB - Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing toward the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies. PMID- 26876139 TI - Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia. AB - Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main contributor to enhanced recovery of motor ability after neonatal HI. PMID- 26876140 TI - Neonatal exposure to whole body ionizing radiation induces adult neurobehavioural defects: Critical period, dose--response effects and strain and sex comparison. AB - Development of the brain includes periods which can be critical for its normal maturation. The present study investigates specifically vulnerable peri /postnatal periods in mice which are essential for understanding the etiology behind radiation induced neurotoxicity and functional defects, including evaluation of neurotoxicity between sexes or commonly used laboratory mouse strains following low/moderate doses of ionizing radiation (IR). Male Naval Medical Research Institute (NMRI) mice, whole body irradiated to a single 500 mGy IR dose, on postnatal day (PND) 3 or PND 10 showed an altered adult spontaneous behaviour and impaired habituation capacity, whereas irradiation on PND 19 did not have any impact on the studied variables. Both NMRI and C57bl/6 male and female mice showed an altered adult spontaneous behaviour and impaired habituation following a single whole body irradiation of 500 or 1000 mGy, but not after 20 or 100 mGy, on PND 10. The present study shows that exposure to low/moderate doses of IR during critical life stages might be involved in the induction of neurological/neurodegenerative disorder/disease. A specifically vulnerable period for radiation induced neurotoxicity seems to be around PND 3-10 in mice. Further studies are needed to investigate mechanisms involved in induction of developmental neurotoxicity following low-dose irradiation. PMID- 26876141 TI - The dog nose "KNOWS" fear: Asymmetric nostril use during sniffing at canine and human emotional stimuli. AB - Previous studies have reported striking asymmetries in the nostril use of dogs during sniffing at different emotive stimuli. Here we report, for the first time, that this asymmetry is also manifested during sniffing of both human and canine odours collected during different emotional events. Results showed that during sniffing of conspecific odour collected during a stressful situation (e.g. an "isolation" situation in which a dog was isolated from its owner in an unfamiliar environment) dogs consistently used their right nostril (right hemisphere). On the other hand, dogs consistently used the left nostril to sniff human odours collected during fearful situations (emotion-eliciting movies) and physical stress, suggesting the prevalent activation of the left hemisphere. The opposite bias shown in nostril use during sniffing at canine versus human odours suggests that chemosignals communicate conspecific and heterospecific emotional cues using different sensory pathways. PMID- 26876142 TI - Pregnancy outcomes following the use of thiocolchicoside. AB - Thiocolchicoside is a commonly used muscle relaxant in orthopedic, rheumatologic or musculoskeletal disorders to treat painful muscle spasms. It is contraindicated in pregnancy and lactation. There is no previously published experience with thiocolchicoside exposure during pregnancy. In this observational study, we collected and evaluated 18 pregnancy outcomes of the women referred to our prenatal consultation service for thiocolchicoside exposure between 2007 2012, and offspring were followed up until 2 years of age. There were 16 live births, 1 spontaneous abortion and 1 elective termination of pregnancy. No major birth defect was observed. The mothers and their babies were free of perinatal complications. No growth or developmental abnormalities were found during follow up period. Our findings add information on inadvertent use of thiocolchicoside in pregnancy. Further large prospective cohort studies are required to investigate this issue. PMID- 26876143 TI - Angiotensin receptor-1A knockout leads to hydronephrosis not associated with a loss of pyeloureteric peristalsis in the mouse renal pelvis. AB - The action of angiotensin II (AngII) on the Ca(2+) signals driving pyeloureteric peristalsis was investigated using both conventional and angiotensin receptor (ATr) ATr1A and ATr2 knockout ((-/-)) mice. Contractility in the renal pelvis of adult ATr1A(-/-) and ATr2(-/-) mice was compared to their respective wildtype (ATr1A(+/+) and ATr2(+/+)) controls of the same genetic background (FVB/N and C57Bl/6 respectively) using video microscopy. The effects of AngII on the Ca(2+) signals in typical and atypical smooth muscle cells (TSMCs and ASMCs, respectively) within the pelvic wall of conventional mice were recorded using Fluo-4 Ca(2+) imaging. Compared to ATr1A(+/+) , ATr2(+/+) and ATr2(-/-) mice, kidneys of the ATr1A(-/-) mouse were mildly-to-severely hydronephrotic, associated with an enlarged calyx, an atrophic papilla and a hypoplastic renal pelvis. Contraction frequencies in the renal pelvis of moderately hydronephrotic ATr1A(-/-) and unaffected ATr2(-/-) mice were not significantly different from their ATr1A(+/+), ATr2(+/+) controls. No contractions were observed in severely hydronephrotic ATr1A(-/-) kidneys. AngII increased the spontaneous contraction frequency of the renal pelvis in ATr1A(+/+), ATr2(+/+) and ATr2(-/-) mice, but had little effect on the contractions in the mildly-hydronephrotic ATr1A(-/-) renal pelvis. The ATr1 blocker, candesartan prevented the positive chronotropic effects of AngII. AngII increased the frequency and synchronicity of Ca(2+) transients in both TSMCs and ASMCs. It was concluded that the hydronephrosis observed in ATr1A(-/-) mouse kidneys does not arise from a failure in the development of the essential pacemaker and contractile machinery driving pyeloureteric peristalsis. PMID- 26876144 TI - Osteogenesis effect of guided bone regeneration combined with alveolar cleft grafting: assessment by cone beam computed tomography. AB - Cone beam computed tomography (CBCT) allows for a significantly lower radiation dose than conventional computed tomography (CT) scans and provides accurate images of the alveolar cleft area. The osteogenic effect of guided bone regeneration (GBR) vs. conventional alveolar bone grafting alone for alveolar cleft defects was evaluated in this study. Sixty alveolar cleft patients were divided randomly into two groups. One group underwent GBR using acellular dermal matrix film combined with alveolar bone grafting using iliac crest bone grafts (GBR group), while the other group underwent alveolar bone grafting only (non-GBR group). CBCT images were obtained at 1 week and at 3 months following the procedure. Using Simplant 11.04 software, the bone resorption rate was calculated and compared between the two groups. The bone resorption rate from 1 week to 3 months following bone grafting without the GBR technique was 36.50+/-5.04%, whereas the bone resorption rate using the GBR technique was 31.69+/-5.50% (P=0.017). The application of autogenous iliac bone combined with the GBR technique for alveolar bone grafting of alveolar cleft patients can reduce bone resorption and result in better osteogenesis. PMID- 26876145 TI - Successful treatment of primary cutaneous Nocardia brasiliensis infection with oral potassium iodide. PMID- 26876146 TI - Cholesteryl ester transfer between lipoproteins does not require a ternary tunnel complex with CETP. AB - The cholesteryl ester transfer protein (CETP) enables the transfer of cholesteryl ester (CE) from high-density lipoproteins (HDL) to low-density lipoproteins (LDL) in the plasma compartment. CETP inhibition raises plasma levels of HDL cholesterol; a ternary tunnel complex with CETP bridging HDL and LDL was suggested as a mechanism. Here, we test whether the inhibition of CETP tunnel complex formation is a promising approach to suppress CE transfer from HDL to LDL, for potential treatment of cardio-vascular disease (CVD). Three monoclonal antibodies against different epitopes of CETP are assayed for their potential to interfere with CE transfer between HDL and/or LDL. Surprisingly, antibodies that target the tips of the elongated CETP molecule, interaction sites sterically required to form the suggested transfer complexes, do not interfere with CETP activity, but an antibody binding to the central region does. We show that CETP interacts with HDL, but not with LDL. Our findings demonstrate that a ternary tunnel complex is not the mechanistic prerequisite to transfer CE among lipoproteins. PMID- 26876148 TI - An improved cryo-FIB method for fabrication of frozen hydrated lamella. AB - Cryo-electron tomography (cryo-ET) provides great insights into the ultrastructure of cells and tissues in their native state and provides a promising way to study the in situ 3D structures of macromolecular complexes. However, this technique has been limited on the very thin specimen, which is not applicable for most cells and tissues. Besides cryo-sectioning approach, cryo focused ion beam (cryo-FIB) appeared recently to achieve 'artifact-free' thin frozen hydrated lamella via fabrication. Considering that the current cryo-FIB methods need modified holders or cartridges, here, with a "D-shaped" molybdenum grid and a specific shutter system, we developed a simple cryo-FIB approach for thin frozen hydrated lamella fabrication, which fits both standard transmission cryo-electron microscopes with side-entry cryo-holders and state-of-the-art ones with AutoGrids. Our approach will expand the usage of cryo-FIB approach in many labs. PMID- 26876147 TI - X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action. AB - The anti-arthritic gold-containing drug Auranofin is lethal to the protozoan intestinal parasite Entamoeba histolytica, the causative agent of human amebiasis, in both culture and animal models of the disease. A putative mechanism of Auranofin action proposes that monovalent gold, Au(I), released from the drug, can bind to the redox-active dithiol group of thioredoxin reductase (TrxR). Au(I) binding in the active site is expected to prevent electron transfer to the downstream substrate thioredoxin (Trx), thus interfering with redox homeostasis in the parasite. To clarify the molecular mechanism of Auranofin action in more detail, we determined a series of atomic resolution X-ray structures for E. histolytica thioredoxin (EhTrx) and thioredoxin reductase (EhTrxR), the latter with and without Auranofin. Only the disulfide-bonded form of the active site dithiol (Cys(140)-Cys(143)) was invariably observed in crystals of EhTrxR in spite of the addition of reductants in various crystallization trials, and no gold was found associated with these cysteines. Non-catalytic Cys(286) was identified as the only site of modification, but further mutagenesis studies using the C286Q mutant demonstrated that this site was not responsible for inhibition of EhTrxR by Auranofin. Interestingly, we obtained both of the catalytically-relevant conformations of this bacterial-like, low molecular weight TrxR in crystals without requiring an engineered disulfide linkage between Cys mutants of TrxR and Trx (as was originally done with Escherichia coli TrxR and Trx). We note that the -CXXC- catalytic motif, even if reduced, would likely not provide space sufficient to bind Au(I) by both cysteines of the dithiol group. PMID- 26876149 TI - Differential expression of GDF-9 and BMP- 15 during follicular development in canine ovaries evaluated by flow cytometry. AB - Growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP 15) play important functions in follicular and oocyte development in many species. This study evaluated the dynamic expression of GDF-9 and BMP-15 in canine follicles cells using flow cytometry analysis. Follicular cells were removed from three sizes of antral follicles (small, medium and large) from ovaries of bitches throughout the estrus cycle. Cells were incubated with anti human GDF-9 polyclonal and anti-mouse BMP-15 monoclonal antibodies. A size and complexity discriminatory gate was used for the cytometryc analysis in the initial dot plot and, additionally, a CD45 marker for leukocyte and propidium iodide (PI) were used for erythrocyte and debris discrimination. The evidence corroborated the presence of both proteins in canine follicle cells, but these proteins were not expressed equally during follicular development. The results analyzed by ANOVA showed that GDF-9 expression decreased (P<0.05) during follicular growth in anestrus and proestrous/estrous, but increased in diestrus (P<0.05). The expression levels of BMP-15 rose (P<0.05) from small to medium sizes in anestrous without changing at diestrus. Small antral follicles expressed the highest values of GDF-9 at anestrus while only BMP-15 showed higher value in small antral follicles at proestrous-estrus compared to diestrus and anestrus. Both proteins decreased in proestrous/estrous (P<0.05) with increasing follicle size, registering the lowest levels in large follicles. The flow cytometric assay was able to assess GDF-9 and BMP-15 expression in canine follicular cells, showing that these proteins were differentially expressed during follicular development, possibly related to the special features of canine reproduction. PMID- 26876150 TI - A network including TGFbeta/Smad4, Gata2, and p57 regulates proliferation of mouse hematopoietic progenitor cells. AB - Transforming growth factor beta (TGFbeta) is a potent inhibitor of hematopoietic stem and progenitor cell proliferation. However, the precise mechanism for this effect is unknown. Here, we have identified the transcription factor Gata2, previously described as an important regulator of hematopoietic stem cell function, as an early and direct target gene for TGFbeta-induced Smad signaling in hematopoietic progenitor cells. We also report that Gata2 is involved in mediating a significant part of the TGFbeta response in primitive hematopoietic cells. Interestingly, the cell cycle regulator and TGFbeta signaling effector molecule p57 was found to be upregulated as a secondary response to TGFbeta. We observed Gata2 binding upstream of the p57 genomic locus, and importantly, loss of Gata2 abolished TGFbeta-stimulated induction of p57 as well as the resulting growth arrest of hematopoietic progenitors. Our results connect key molecules involved in hematopoietic stem cell self-renewal and reveal a functionally relevant network, regulating proliferation of primitive hematopoietic cells. PMID- 26876151 TI - Hippocampal subfield volumetry in patients with subcortical vascular mild cognitive impairment. AB - Memory impairment is a typical characteristic of patients with subcortical vascular mild cognitive impairment (svMCI) or with amnestic mild cognitive impairment (aMCI). The hippocampus, which plays an important role in the consolidation of information from short-term memory to long-term memory, is a heterogeneous structure that consists of several anatomically and functionally distinct subfields. However, whether distinct hippocampal subfields are differentially and selectively affected by svMCI pathology and whether these abnormal changes in hippocampal subfields are different between svMCI and aMCI patients are largely unknown. A total of 26 svMCI patients, 26 aMCI patients and 26 healthy controls matched according to age, gender and years of education were enrolled in this study. We utilized an automated hippocampal subfield segmentation method provided by FreeSurfer to estimate the volume of several hippocampal subfields, including the cornu ammonis (CA) areas, the dentate gyrus (DG), the subiculum and the presubiculum. Compared with controls, the left subiculum and presubiculum and the right CA4/DG displayed significant atrophy in patients with svMCI. Interestingly, we also found significant differences in the volume of the right CA1 between the svMCI and aMCI groups. Taken together, our results reveal region-specific vulnerability of hippocampal subfields to svMCI pathology and identify distinct hippocampal subfield atrophy patterns between svMCI and aMCI patients. PMID- 26876152 TI - UVB Generates Microvesicle Particle Release in Part Due to Platelet-activating Factor Signaling. AB - The lipid mediator platelet-activating factor (PAF) and oxidized glycerophosphocholine PAF agonists produced by ultraviolet B (UVB) have been demonstrated to play a pivotal role in UVB-mediated processes, from acute inflammation to delayed systemic immunosuppression. Recent studies have provided evidence that microvesicle particles (MVPs) are released from cells in response to various signals including stressors. Importantly, these small membrane fragments can interact with various cell types by delivering bioactive molecules. The present studies were designed to test if UVB radiation can generate MVP release from epithelial cells, and the potential role of PAF receptor (PAF-R) signaling in this process. We demonstrate that UVB irradiation of the human keratinocyte-derived cell line HaCaT resulted in the release of MVPs. Similarly, treatment of HaCaT cells with the PAF-R agonist carbamoyl PAF also generated equivalent amounts of MVP release. Of note, pretreatment of HaCaT cells with antioxidants blocked MVP release from UVB but not PAF-R agonist N-methyl carbamyl PAF (CPAF). Importantly, UVB irradiation of the PAF-R-negative human epithelial cell line KB and KB transduced with functional PAF-Rs resulted in MVP release only in PAF-R-positive cells. These studies demonstrate that UVB can generate MVPs in vitro and that PAF-R signaling appears important in this process. PMID- 26876153 TI - Role of C-N Configurations in the Photoluminescence of Graphene Quantum Dots Synthesized by a Hydrothermal Route. AB - Graphene quantum dots (GQDs) containing N atoms were successfully synthesized using a facile, inexpensive, and environmentally friendly hydrothermal reaction of urea and citric acid, and the effect of the GQDs' C-N configurations on their photoluminescence (PL) properties were investigated. High-resolution transmission electron microscopy (HR-TEM) images confirmed that the dots were spherical, with an average diameter of 2.17 nm. X-ray photoelectron spectroscopy (XPS) analysis indicated that the C-N configurations of the GQDs substantially affected their PL intensity. Increased PL intensity was obtained in areas with greater percentages of pyridinic-N and lower percentages of pyrrolic-N. This enhanced PL was attributed to delocalized pi electrons from pyridinic-N contributing to the C system of the GQDs. On the basis of energy electron loss spectroscopy (EELS) and UV-Vis spectroscopy analyses, we propose a PL mechanism for hydrothermally synthesized GQDs. PMID- 26876156 TI - Observation of the Kibble-Zurek Mechanism in Microscopic Acoustic Crackling Noises. AB - Characterizing the fast evolution of microstructural defects is key to understanding "crackling" phenomena during the deformation of solid materials. For example, it has been proposed using atomistic simulations of crack propagation in elastic materials that the formation of a nonlinear hyperelastic or plastic zone around moving crack tips controls crack velocity. To date, progress in understanding the physics of this critical zone has been limited due to the lack of data describing the complex physical processes that operate near microscopic crack tips. We show, by analyzing many acoustic emission events during rock deformation experiments, that the signature of this nonlinear zone maps directly to crackling noises. In particular, we characterize a weakening zone that forms near the moving crack tips using functional networks, and we determine the scaling law between the formation of damages (defects) and the traversal rate across the critical point of transition. Moreover, we show that the correlation length near the transition remains effectively frozen. This is the main underlying hypothesis behind the Kibble-Zurek mechanism (KZM) and the obtained power-law scaling verifies the main prediction of KZM. PMID- 26876155 TI - Lovastatin protects keratinocytes from DNA damage-related pro-apoptotic stress responses stimulated by anticancer therapeutics. AB - BACKGROUND: Oral mucositis (OM) is a relevant adverse effect of anticancer therapy involving ionizing radiation (IR) and doxorubicin (Doxo). Because DNA damage of keratinocytes is causative for the pathogenesis of OM, we aim to identify pharmacological measures for geno- and cytoprotection of keratinocytes. METHODS: We investigated the influence of the lipid-lowering drug lovastatin on cell death, proliferation and DNA damage response (DDR) mechanisms of human keratinocytes following treatment with IR and Doxo. RESULTS: Lovastatin protected keratinocytes from the cytotoxic and genotoxic effects of IR and Doxo as shown by a diminished induction of apoptosis as well as a reduced formation and slightly improved repair of DNA damage following Doxo and IR treatment, respectively. Lovastatin selectively blocked the activation of Chk1 and ATR kinases following treatment with IR, Doxo and the ribonucleotide reductase inhibitor hydroxyurea, indicating that the statin antagonizes ATR/Chk1-regulated replicative stress responses. Part of the cytoprotective activity of lovastatin seems to rest on a delayed entry of lovastatin treated cells into S-phase. Yet, because the statin also protected non-proliferating keratinocytes from IR- and Doxo-induced cytotoxicity, cell cycle independent protective mechanisms are involved, too. CONCLUSIONS: Lovastatin attenuates pro-toxic DNA damage-related responses of keratinocytes stimulated by OM-inducing anticancer therapeutics. The data encourage forthcoming in vivo and clinical studies addressing the usefulness of statins in the prevention of OM. PMID- 26876154 TI - Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1. AB - In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells. PMID- 26876157 TI - Cost-conscious decisions in the timing of operation for minimally symptomatic inguinal hernias in male patients. AB - BACKGROUND: Expectant management (EM) and early open repair (OR) are safe and effective as initial management strategies for minimally symptomatic inguinal hernia in male patients. Extended follow-up of patients in EM protocols have shown that most patients will eventually require repair, but it is not clear which strategy is less costly over the long term. METHODS: We constructed a mathematical model to compare 3rd-party payer expenditures for EM vs OR or laparoscopic repair in a simulated cohort of patients with inguinal hernia. Cohort characteristics and expenditures were calibrated to recent randomized trials that reported initial follow-up and expenditures at 2 years and long-term crossover rates from EM to OR. RESULTS: Cost comparisons between OR and EM are sensitive to direct long-term costs of inpatient and outpatient care, the likelihood of crossover from EM to operation, cost differences between OR and laparoscopic repair, and the net present value of longer-term costs. CONCLUSIONS: Our findings suggest that short-term costs of EM are less than those of OR and Lap-R, but early OR provides the highest long-term savings. PMID- 26876158 TI - Development of Helisoma trivolvis pond snails as biological samplers for biomonitoring of current-use pesticides. AB - Nontarget aquatic organisms residing in wetlands are commonly exposed to current use pesticides through spray drift and runoff. However, it is frequently challenging to measure exposure because of rapid dissipation of pesticides from water and reduced bioavailability. The authors' hypothesis is that freshwater snails can serve as bioindicators of pesticide exposure based on their capacity to passively accumulate tissue residues. Helisoma trivolvis snails were evaluated as biomonitors of pesticide exposure using a fungicide formulation that contains pyraclostrobin and metconazole and is frequently applied to crops surrounding depressional wetlands. Exposure-response studies indicate that H. trivolvis are tolerant of pyraclostrobin and metconazole at concentrations >10 times those lethal to many aquatic species, with a median lethal concentration based on pyraclostrobin of 441 MUg/L (95% confidence interval of 359-555 MUg/L). Bioconcentration factors ranged from 137 mL/g to 211 mL/g and from 39 mL/g to 59 mL/g for pyraclostrobin and metconazole, respectively. Elimination studies suggested one-compartmental elimination and snail tissue half-lives (t50 ) of approximately 15 h and 5 h for pyraclostrobin and metconazole, respectively. Modeling derived toxicokinetic parameters in the context of an environmentally relevant pulsed exposure suggests that residues can be measured in snails long after water concentrations fall below detection limits. With high fungicide tolerance, rapid accumulation, and slow elimination, H. trivolvis may be viable for biomonitoring of pyraclostrobin and should be investigated for other pesticides. Environ Toxicol Chem 2016;35:2320-2329. (c) 2016 SETAC. PMID- 26876159 TI - The Impact of Pain and Itch on Functioning and Health-Related Quality of Life in Systemic Sclerosis: An Exploratory Study. AB - CONTEXT: Pain and itch are common symptoms reported by patients with systemic sclerosis (SSc; scleroderma), which can markedly diminish function and health related quality of life (HRQL). OBJECTIVES: The aim of this exploratory study was to examine the impact that pain, itch, and the interaction of both have on function (depressive symptoms, overall disability, fatigue, sleep disturbance) and HRQL in patients with SSc. METHODS: A total of 964 patients from the Canadian Scleroderma Reserch Group Registry completed questionnaires measuring itch and pain severity, function, and HRQL. Multiple regression analyses were performed to examine the impact that pain, itch, and pain * itch interaction have on each outcome variable while controlling for demographic measures. A P-value of <=0.01 was required for a difference to be deemed statistically significant. RESULTS: Our results revealed that patients with SSc who reported higher pain and itch severity were also more likely to have greater depressive symptoms, overall disability, sleep and fatigue problems, even when demographic measures were controlled for (P-values <=0.001). Similar results were obtained for HRQL, regardless of the domains (P-values <=0.001). A significant association between pain * itch interaction and sleep (P = 0.002), physical functioning (P = 0.003), and general health (P <= 0.001) variables also was found. Further investigation of the nature of the pain * itch interaction showed that the effect of pain severity on outcome variables diminishes as itch severity increases. CONCLUSION: Both pain and itch appear to have a detrimental impact on functioning and HRQL in patients with SSc, suggesting that more targeted approaches to symptom management are warranted. PMID- 26876160 TI - Bioactivity, proximate, mineral and volatile profiles along the flowering stages of Opuntia microdasys (Lehm.): defining potential applications. AB - Opuntia spp. flowers have been traditionally used for medical purposes, mostly because of their diversity in bioactive molecules with health promoting properties. The proximate, mineral and volatile compound profiles, together with the cytotoxic and antimicrobial properties were characterized in O. microdasys flowers at different maturity stages, revealing several statistically significant differences. O. microdasys stood out mainly for its high contents of dietary fiber, potassium and camphor, and its high activities against HCT15 cells, Staphylococcus aureus, Aspergillus versicolor and Penicillium funiculosum. The vegetative stage showed the highest cytotoxic and antifungal activities, whilst the full flowering stage was particularly active against bacterial species. The complete dataset has been classified by principal component analysis, achieving clearly identifiable groups for each flowering stage, elucidating also the most distinctive features, and comprehensively profiling each of the assayed stages. The results might be useful to define the best flowering stage considering practical application purposes. PMID- 26876161 TI - AnnoTALE: bioinformatics tools for identification, annotation, and nomenclature of TALEs from Xanthomonas genomic sequences. AB - Transcription activator-like effectors (TALEs) are virulence factors, produced by the bacterial plant-pathogen Xanthomonas, that function as gene activators inside plant cells. Although the contribution of individual TALEs to infectivity has been shown, the specific roles of most TALEs, and the overall TALE diversity in Xanthomonas spp. is not known. TALEs possess a highly repetitive DNA-binding domain, which is notoriously difficult to sequence. Here, we describe an improved method for characterizing TALE genes by the use of PacBio sequencing. We present 'AnnoTALE', a suite of applications for the analysis and annotation of TALE genes from Xanthomonas genomes, and for grouping similar TALEs into classes. Based on these classes, we propose a unified nomenclature for Xanthomonas TALEs that reveals similarities pointing to related functionalities. This new classification enables us to compare related TALEs and to identify base substitutions responsible for the evolution of TALE specificities. PMID- 26876162 TI - Non-equilibrium behaviour in coacervate-based protocells under electric-field induced excitation. AB - Although numerous strategies are now available to generate rudimentary forms of synthetic cell-like entities, minimal progress has been made in the sustained excitation of artificial protocells under non-equilibrium conditions. Here we demonstrate that the electric field energization of coacervate microdroplets comprising polylysine and short single strands of DNA generates membrane-free protocells with complex, dynamical behaviours. By confining the droplets within a microfluidic channel and applying a range of electric field strengths, we produce protocells that exhibit repetitive cycles of vacuolarization, dynamical fluctuations in size and shape, chaotic growth and fusion, spontaneous ejection and sequestration of matter, directional capture of solute molecules, and pulsed enhancement of enzyme cascade reactions. Our results highlight new opportunities for the study of non-equilibrium phenomena in synthetic protocells, provide a strategy for inducing complex behaviour in electrostatically assembled soft matter microsystems and illustrate how dynamical properties can be activated and sustained in microcompartmentalized media. PMID- 26876163 TI - Web-based volume slicer for 3D electron-microscopy data from EMDB. AB - We describe the functionality and design of the Volume slicer - a web-based slice viewer for EMDB entries. This tool uniquely provides the facility to view slices from 3D EM reconstructions along the three orthogonal axes and to rapidly switch between them and navigate through the volume. We have employed multiple rounds of user-experience testing with members of the EM community to ensure that the interface is easy and intuitive to use and the information provided is relevant. The impetus to develop the Volume slicer has been calls from the EM community to provide web-based interactive visualisation of 2D slice data. This would be useful for quick initial checks of the quality of a reconstruction. Again in response to calls from the community, we plan to further develop the Volume slicer into a fully-fledged Volume browser that provides integrated visualisation of EMDB and PDB entries from the molecular to the cellular scale. PMID- 26876164 TI - Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers. AB - The prognosis associated with clear cell renal carcinoma (ccRCC) can vary widely and novel molecular prognostic markers are needed to assess prognosis at an earlier stage. Several gene products have been investigated for this purpose, but none of them have been implemented in clinical practice. Here we hypothesized that we, using TaqMan(r) Array, could identify superior prognostic messenger RNA (mRNA)s in long-term follow-up. Messenger RNA level of 19 candidate genes was investigated in 97 patients with ccRCC. Three genes impacted significantly on prognosis in both univariate and multivariate analysis. In univariate analysis, CSNK2A1 was a strong indicator of a poor overall survival (OS) (HR = 5.01, p < 0.001), disease specific survival (DSS) (HR = 6.21, p = 0.007) and progression free survival (PFS) (HR = 5.93, p = 0.005). High expression of SPP1 was associated to poor PFS (HR = 4.41, p = 0.04). DEFB1 was associated with a better PFS (HR = 0.24, p = 0.006). In multivariate analysis, CSNK2A1 was associated to a worse OS (HR = 3.56, p = 0.008) and PFS (HR = 3.84, p = 0.005), whereas SPP1 was an independent predictor of a worse PFS (HR = 3.46, p = 0.007) and DEFB1 of a better PFS (HR = 0.37, p = 0.027). These results show that with TaqMan(r)) Array we could identify three superior gene products related to prognosis. Further studies are needed to elucidate the pathways and roles of these genes in renal cacer development. PMID- 26876165 TI - Differential Regulation of Interferon Responses by Ebola and Marburg Virus VP35 Proteins. AB - Suppression of innate immune responses during filoviral infection contributes to disease severity. Ebola (EBOV) and Marburg (MARV) viruses each encode a VP35 protein that suppresses RIG-I-like receptor signaling and interferon-alpha/beta (IFN-alpha/beta) production by several mechanisms, including direct binding to double stranded RNA (dsRNA). Here, we demonstrate that in cell culture, MARV infection results in a greater upregulation of IFN responses as compared to EBOV infection. This correlates with differences in the efficiencies by which EBOV and MARV VP35s antagonize RIG-I signaling. Furthermore, structural and biochemical studies suggest that differential recognition of RNA elements by the respective VP35 C-terminal IFN inhibitory domain (IID) rather than affinity for RNA by the respective VP35s is critical for this observation. Our studies reveal functional differences in EBOV versus MARV VP35 RNA binding that result in unexpected differences in the host response to deadly viral pathogens. PMID- 26876167 TI - Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity. AB - Mitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis. PMID- 26876166 TI - MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1. AB - MicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement. PMID- 26876168 TI - C. elegans Body Cavity Neurons Are Homeostatic Sensors that Integrate Fluctuations in Oxygen Availability and Internal Nutrient Reserves. AB - It is known that internal physiological state, or interoception, influences CNS function and behavior. However, the neurons and mechanisms that integrate sensory information with internal physiological state remain largely unknown. Here, we identify C. elegans body cavity neurons called URX(L/R) as central homeostatic sensors that integrate fluctuations in oxygen availability with internal metabolic state. We show that depletion of internal body fat reserves increases the tonic activity of URX neurons, which influences the magnitude of the evoked sensory response to oxygen. These responses are integrated via intracellular cGMP and Ca(2+). The extent of neuronal activity thus reflects the balance between the perception of oxygen and available fat reserves. The URX homeostatic sensor ensures that neural signals that stimulate fat loss are only deployed when there are sufficient fat reserves to do so. Our results uncover an interoceptive neuroendocrine axis that relays internal state information to the nervous system. PMID- 26876169 TI - The C. elegans CCAAT-Enhancer-Binding Protein Gamma Is Required for Surveillance Immunity. AB - Pathogens attack host cells by deploying toxins that perturb core host processes. Recent findings from the nematode C. elegans and other metazoans indicate that surveillance or "effector-triggered" pathways monitor functioning of these core processes and mount protective responses when they are perturbed. Despite a growing number of examples of surveillance immunity, the signaling components remain poorly defined. Here, we show that CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity. We show that CEBP-2 acts together with the bZIP transcription factor ZIP-2 in the protective response to translational block by P. aeruginosa Exotoxin A as well as perturbations of other processes. CEBP-2 serves to limit pathogen burden, promote survival upon P. aeruginosa infection, and also promote survival upon Exotoxin A exposure. These findings may have broad implications for the mechanisms by which animals sense pathogenic attack and mount protective responses. PMID- 26876170 TI - Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence. AB - The hallmarks of age-related immune senescence are chronic inflammation, aberrant expansion of effector memory, and loss of naive T lymphocytes due in part to systemic activation of innate immune sensor NLRP3 inflammasome in myeloid lineage cells. The endogenous mechanisms that regulate inflammasome activation during aging are unknown. Here, we present evidence that growth hormone receptor (GH-R) dependent downregulation of NLRP3 inflammasome in macrophages is linked to pro longevity effects that maintain immune system homeostasis in aging. Deletion of GH-R prevented the macrophage-driven age-related activation of inflammasome in response to NLRP3 ligands and also increased the preservation of naive T cells, even in advanced age and with higher IFNgamma secretion from effector cells. The mechanism of inflammasome inhibition is linked to autocrine somatotropic axis as ablation of IGF1R in macrophages lowered the NLRP3 inflammasome activation. Together, our findings show that functional somatotropic axis in macrophages controls inflammation, thus linking NLRP3-mediated innate immune signaling to health span and longevity. PMID- 26876171 TI - Targeting Macrophages Sensitizes Chronic Lymphocytic Leukemia to Apoptosis and Inhibits Disease Progression. AB - The role of monocytes/macrophages in the development and progression of chronic lymphocytic leukemia (CLL) is poorly understood. Transcriptomic analyses show that monocytes/macrophages and leukemic cells cross talk during CLL progression. Macrophage depletion impairs CLL engraftment, drastically reduces leukemic growth, and favorably impacts mouse survival. Targeting of macrophages by either CSF1R signaling blockade or clodrolip-mediated cell killing has marked inhibitory effects on established leukemia also. Macrophage killing induces leukemic cell death mainly via the TNF pathway and reprograms the tumor microenvironment toward an antitumoral phenotype. CSF1R inhibition reduces leukemic cell load, especially in the bone marrow, and increases circulating CD20(+) leukemic cells. Accordingly, co-targeting TAMs and CD20-expressing leukemic cells provides a survival benefit in the mice. These results establish the important role of macrophages in CLL and suggest therapeutic strategies based on interfering with leukemia-macrophage interactions. PMID- 26876173 TI - An ER-Localized SNARE Protein Is Exported in Specific COPII Vesicles for Autophagosome Biogenesis. AB - The de novo formation of autophagosomes for the targeting of cytosolic material to the vacuole/lysosome is upregulated upon starvation. How autophagosomes acquire membranes remains still unclear. Here, we report that, in yeast, the endoplasmic reticulum (ER)-localized Qa/t-SNARE Ufe1 has a role in autophagy. During starvation, Ufe1 is increasingly exported from the ER and targeted to intracellular sites that contain the autophagy markers Atg8 and Atg9. In addition, Ufe1 interacts with non-ER SNARE proteins implicated in autophagosome formation. Loss of Ufe1 function impairs autophagy and results in fewer and smaller autophagosomes. Unlike conventional cargo, the ER export of Ufe1 is significantly reduced in sec23-1 cells, which affects the coat protein (COP)II complex, already at the permissive temperature. Under the same conditions, sec23 1 cells are hypersensitive to starvation and deficient in autophagy. Our data suggest that ER membranes containing Ufe1 are delivered to sites of autophagosome formation in specific COPII vesicles. PMID- 26876172 TI - Satb1 Overexpression Drives Tumor-Promoting Activities in Cancer-Associated Dendritic Cells. AB - Special AT-rich sequence-binding protein 1 (Satb1) governs genome-wide transcriptional programs. Using a conditional knockout mouse, we find that Satb1 is required for normal differentiation of conventional dendritic cells (DCs). Furthermore, Satb1 governs the differentiation of inflammatory DCs by regulating major histocompatibility complex class II (MHC II) expression through Notch1 signaling. Mechanistically, Satb1 binds to the Notch1 promoter, activating Notch expression and driving RBPJ occupancy of the H2-Ab1 promoter, which activates MHC II transcription. However, tumor-driven, unremitting expression of Satb1 in activated Zbtb46(+) inflammatory DCs that infiltrate ovarian tumors results in an immunosuppressive phenotype characterized by increased secretion of tumor promoting Galectin-1 and IL-6. In vivo silencing of Satb1 in tumor-associated DCs reverses their tumorigenic activity and boosts protective immunity. Therefore, dynamic fluctuations in Satb1 expression govern the generation and immunostimulatory activity of steady-state and inflammatory DCs, but continuous Satb1 overexpression in differentiated DCs converts them into tolerogenic/pro inflammatory cells that contribute to malignant progression. PMID- 26876174 TI - Intralymphatic CCL21 Promotes Tissue Egress of Dendritic Cells through Afferent Lymphatic Vessels. AB - To induce adaptive immunity, dendritic cells (DCs) migrate through afferent lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively crawl into downstream collecting vessels. From there, they are next passively and rapidly transported to the dLN by lymph flow. Here, we describe a role for the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely abolished DC migration from capillaries toward collecting vessels and reduced the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial monolayers, thereby inducing downstream-directed DC migration. These findings reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through the formation of a flow-induced gradient. PMID- 26876175 TI - RONIN Is an Essential Transcriptional Regulator of Genes Required for Mitochondrial Function in the Developing Retina. AB - A fundamental principle governing organ size and function is the fine balance between cell proliferation and cell differentiation. Here, we identify RONIN (THAP11) as a key transcriptional regulator of retinal progenitor cell (RPC) proliferation. RPC-specific loss of Ronin results in a phenotype strikingly similar to that resulting from the G1- to S-phase arrest and photoreceptor degeneration observed in the Cyclin D1 null mutants. However, we determined that, rather than regulating canonical cell-cycle genes, RONIN regulates a cohort of mitochondrial genes including components of the electron transport chain (ETC), which have been recently implicated as direct regulators of the cell cycle. Coincidentally, with premature cell-cycle exit, Ronin mutants exhibited deficient ETC activity, reduced ATP levels, and increased oxidative stress that we ascribe to specific loss of subunits within complexes I, III, and IV. These data implicate RONIN as a positive regulator of mitochondrial gene expression that coordinates mitochondrial activity and cell-cycle progression. PMID- 26876176 TI - Dynamics of CDKN1A in Single Cells Defined by an Endogenous Fluorescent Tagging Toolkit. AB - Observing the endogenous abundance, localization, and dynamics of proteins in mammalian cells is crucial to understanding their function and behavior. Currently, there is no systematic approach for the fluorescent tagging of endogenous loci. Here, we used Cas9-catalyzed DNA breaks, short homology arms, and a family of donor plasmids to establish endogenous Fluorescent tagging (eFlut): a low-cost and efficient approach to generating endogenous proteins with fluorescent labels. We validated this protocol on multiple proteins in several cell lines and species and applied our tools to study the cell-cycle inhibitor CDKN1A in single cells. We uncover heterogeneity in the timing and rate of CDKN1A induction post-DNA damage and show that this variability is post transcriptionally regulated, depends on cell-cycle position, and has long-term consequences for cellular proliferation. The tools developed in this study should support widespread study of the dynamics and localization of diverse proteins in mammalian cells. PMID- 26876177 TI - Proteolytic Cleavage Governs Interleukin-11 Trans-signaling. AB - Interleukin (IL)-11 has been shown to be a crucial factor for intestinal tumorigenesis, lung carcinomas, and asthma. IL-11 is thought to exclusively mediate its biological functions through cell-type-specific expression of the membrane-bound IL-11 receptor (IL-11R). Here, we show that the metalloprotease ADAM10, but not ADAM17, can release the IL-11R ectodomain. Chimeric proteins of the IL-11R and the IL-6 receptor (IL-6R) revealed that a small juxtamembrane portion is responsible for this substrate specificity of ADAM17. Furthermore, we show that the serine proteases neutrophil elastase and proteinase 3 can also cleave the IL-11R. The resulting soluble IL-11R (sIL-11R) is biologically active and binds IL-11 to activate cells. This IL-11 trans-signaling pathway can be inhibited specifically by the anti-inflammatory therapeutic compound sgp130Fc. In conclusion, proteolysis of the IL-11R represents a molecular switch that controls the IL-11 trans-signaling pathway and widens the number of cells that can be activated by IL-11. PMID- 26876178 TI - Atypical Protein Kinase C-Dependent Polarized Cell Division Is Required for Myocardial Trabeculation. AB - A hallmark of cardiac development is the formation of myocardial trabeculations exclusively from the luminal surface of the primitive heart tube. Although a number of genetic defects in the endocardium and cardiac jelly disrupt myocardial trabeculation, the role of cell polarization remains unclear. Here, we demonstrate that atypical protein kinase C iota (Prkci) and its interacting partners are localized primarily to the luminal side of myocardial cells of early murine embryonic hearts. A subset of these cells undergoes polarized cell division with the cell division plane perpendicular to the heart's lumen. Disruption of the cell polarity complex by targeted gene mutations results in aberrant mitotic spindle alignment, loss of polarized cardiomyocyte division, and loss of normal myocardial trabeculation. Collectively, these results suggest that, in response to inductive signals, Prkci and its downstream partners direct polarized cell division of luminal myocardial cells to drive trabeculation in the nascent heart. PMID- 26876179 TI - MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4. AB - Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export that when inhibited, enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors, further supporting their use as anti-cancer therapeutics. PMID- 26876180 TI - Folate Acts in E. coli to Accelerate C. elegans Aging Independently of Bacterial Biosynthesis. AB - Folates are cofactors for biosynthetic enzymes in all eukaryotic and prokaryotic cells. Animals cannot synthesize folate and must acquire it from their diet or microbiota. Previously, we showed that inhibiting E. coli folate synthesis increases C. elegans lifespan. Here, we show that restriction or supplementation of C. elegans folate does not influence lifespan. Thus, folate is required in E. coli to shorten worm lifespan. Bacterial proliferation in the intestine has been proposed as a mechanism for the life-shortening influence of E. coli. However, we found no correlation between C. elegans survival and bacterial growth in a screen of 1,000+ E. coli deletion mutants. Nine mutants increased worm lifespan robustly, suggesting specific gene regulation is required for the life-shortening activity of E. coli. Disrupting the biosynthetic folate cycle did not increase lifespan. Thus, folate acts through a growth-independent route in E. coli to accelerate animal aging. PMID- 26876182 TI - Leptin Raises Defended Body Temperature without Activating Thermogenesis. AB - Leptin has been believed to exert its weight-reducing action not only by inducing hypophagia but also by increasing energy expenditure/thermogenesis. Leptin deficient ob/ob mice have correspondingly been thought to be thermogenically limited and to show hypothermia, mainly due to atrophied brown adipose tissue (BAT). In contrast to these established views, we found that BAT is fully functional and that leptin treatment did not increase thermogenesis in wild-type or in ob/ob mice. Rather, ob/ob mice showed a decreased but defended body temperature (i.e., were anapyrexic, not hypothermic) that was normalized to wild type levels after leptin treatment. This was not accompanied by increased energy expenditure or BAT recruitment but, instead, was mediated by decreased tail heat loss. The weight-reducing hypophagic effects of leptin are, therefore, not augmented through a thermogenic effect of leptin; leptin is, however, pyrexic, i.e., it alters centrally regulated thresholds of thermoregulatory mechanisms, in parallel to effects of other cytokines. PMID- 26876181 TI - The Apoptotic Engulfment Machinery Regulates Axonal Degeneration in C. elegans Neurons. AB - Axonal degeneration is a characteristic feature of neurodegenerative disease and nerve injury. Here, we characterize axonal degeneration in Caenorhabditis elegans neurons following laser-induced axotomy. We show that this process proceeds independently of the WLD(S) and Nmnat pathway and requires the axonal clearance machinery that includes the conserved transmembrane receptor CED-1/Draper, the adaptor protein CED-6, the guanine nucleotide exchange factor complex Crk/Mbc/dCed-12 (CED-2/CED-5/CED-12), and the small GTPase Rac1 (CED-10). We demonstrate that CED-1 and CED-6 function non-cell autonomously in the surrounding hypodermis, which we show acts as the engulfing tissue for the severed axon. Moreover, we establish a function in this process for CED-7, an ATP binding cassette (ABC) transporter, and NRF-5, a lipid-binding protein, both associated with release of lipid-vesicles during apoptotic cell clearance. Thus, our results reveal the existence of a WLD(S)/Nmnat-independent axonal degeneration pathway, conservation of the axonal clearance machinery, and a function for CED-7 and NRF-5 in this process. PMID- 26876183 TI - Improved Ribosome-Footprint and mRNA Measurements Provide Insights into Dynamics and Regulation of Yeast Translation. AB - Ribosome-footprint profiling provides genome-wide snapshots of translation, but technical challenges can confound its analysis. Here, we use improved methods to obtain ribosome-footprint profiles and mRNA abundances that more faithfully reflect gene expression in Saccharomyces cerevisiae. Our results support proposals that both the beginning of coding regions and codons matching rare tRNAs are more slowly translated. They also indicate that emergent polypeptides with as few as three basic residues within a ten-residue window tend to slow translation. With the improved mRNA measurements, the variation attributable to translational control in exponentially growing yeast was less than previously reported, and most of this variation could be predicted with a simple model that considered mRNA abundance, upstream open reading frames, cap-proximal structure and nucleotide composition, and lengths of the coding and 5' UTRs. Collectively, our results provide a framework for executing and interpreting ribosome-profiling studies and reveal key features of translational control in yeast. PMID- 26876185 TI - Phase diagram and segregation of Ag-Co nanoalloys: insights from theory and simulation. AB - Understanding the phase diagram is the first step to identifying the structure performance relationship of a material at the nanoscale. In this work, a modified nanothermodynamical model has been developed to predict the phase diagrams of Ag Co nanoalloys with the size of 1 ~ 100 nm, which also overcomes the difference in the predicted results between theory and simulation for the first time. Based on this modified model, the phase diagrams of Ag-Co nanoalloys with various polyhedral morphologies (tetrahedron, cube, octahedron, decahedron, dodecahedron, rhombic dodecahedron, truncated octahedron, cuboctahedron, and icosahedron) have been predicted, showing good agreement with molecular dynamics simulations at the nanoscale of 1 ~ 4 nm. In addition, the surface segregation of Ag-Co nanoalloys has been predicted with a Co-rich core/Ag-rich surface, which is also consistent with the simulation results. Our results highlight a useful roadmap for bridging the difference between theory and simulation in the prediction of the phase diagram at the nanoscale, which will help both theorists and experimentalists. PMID- 26876186 TI - Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjogren's syndrome: findings in serum and minor salivary glands. AB - The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjogren's syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD) by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs) of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS. PMID- 26876184 TI - Genome-wide Analysis Identifies Bcl6-Controlled Regulatory Networks during T Follicular Helper Cell Differentiation. AB - T follicular helper (Tfh) cell is a unique T cell subset specialized in promoting humoral immunity. B-cell lymphoma 6 protein (Bcl6) has been identified as an obligatory transcription factor in Tfh cells; however, the molecular mechanism underlying Bcl6 function remains largely unknown. Here, we defined Bcl6 target genes in Tfh cells by analyzing genome-wide Bcl6 occupancy together with transcriptome profiling. With consensus sequences being different from those in Th9, B cells, and macrophages, Bcl6 binding in Tfh cell was closely associated with a decrease in 5-hydroxymethylcytosine (5hmC). Importantly, Bcl6 promoted Tfh cell differentiation through antagonizing IL-7R (CD127)/signal transducer and activator of transcription (STAT) 5 axis; deletion of the Bcl6 gene in T cells resulted in enhanced IL-7R-STAT5 signaling and substantial expansion of CD127(hi) non-Tfh cells. Thus, our study systemically examines Bcl6-controlled regulatory networks and provides important insights into Bcl6's biological functions in Tfh cells. PMID- 26876187 TI - The role of biomechanical factors in ankylosing spondylitis: the patient's perspective. AB - Biomechanical factors including occupational joint physical stressing and joint injury have been linked to spondyloarthritis. We explored such factors in ankylosing spondylitis (AS). A retrospective, online survey was developed alongside the UK National Ankylosing Spondylitis Society (NASS). Questions on early entheseal symptoms, potential precipitating trauma, sporting activity, and physiotherapy were asked. A total of 1026 patients responded with 44% recalling an instance of injury or trauma as a potential trigger for their AS. After symptom onset, 55% modified sporting activities and 28% reported that the initial AS recommended exercises exacerbated symptoms. Patients report physical trauma, exercise and physiotherapy as potential triggers for AS symptoms. These findings further support the experimental evidence for the role of biomechanical factors in disease. PMID- 26876188 TI - Influence of TNF-alpha inhibition on oxidative stress of rheumatoid arthritis patients. AB - The aim of this study was to assess circulating levels of reactive oxygen metabolites (ROMs) as a marker of oxidative stress in rheumatoid arthritis (RA) patients during an anti-tumor necrosis factor alpha (TNF-alpha) treatment. We enrolled 40 patients with RA (36 females; age 53 +/- 13 yrs) treated with different subcutaneously administered TNF-alpha inhibitors. The oxidative status was determined on the basis of plasma samples taken before, at 24 and 52 weeks of the anti-TNF-alpha treatment. Hydroperoxide levels were measured using the d-ROMs test, a useful clinically proven oxidative stress marker. During the anti-TNF alpha therapy, we observed a significant reduction in serum ROMs levels in RA patients from 33.2 +/- 10 mg H2O2/L at baseline to 29.5 +/- 7 and 29.3 +/- 9 mg H2O2/L, at 24 and 52 weeks, respectively (p<0.05). We also identified a significant correlation between the oxidative stress status and the disease activity score on 28 joints/C-reactive protein and health assessment questionnaire disability index. The results of our study demonstrate that a good control of the disease with anti-TNF-alpha agents can reduce oxidative stress in RA patients. However, further studies of larger patient cohorts are needed to confirm these preliminary data. PMID- 26876189 TI - Color Doppler analysis of female reproductive vasculature in Behcet's disease. AB - Behcet's disease (BD) may affect female reproductive vasculature. We aimed to evaluate Doppler sonographic characteristics of female reproductive vasculature and also ovarian volume, endometrial thickness (EMT) and antral follicle count of BD patients in comparison with a healthy control group. Seventeen premenopausal women aged between 18-45 years with BD, and a control group of 31 age- and body mass index-matched healthy women was included in the study. Uterine, spiral and intraovarian artery blood flow were examined by Doppler sonography in the late follicular phase. Resistance index, pulsatility index and systolic/diastolic ratio were recorded together with ovarian volume, EMT and antral follicle count. In particular this is a pilot study including the evaluation of the spiral and uterine arteries in BD. Doppler sonographic parameters, ovarian volume, EMT and antral follicle count of BD patients and healthy controls were not found to be statistically different. As a result of our analysis, we found similar Doppler sonographic features of both BD patients and the control group. Further studies conducted on a larger sample population with more aggressive BD symptoms may reveal the actual effect of BD on the female reproductive system. PMID- 26876190 TI - Neutrophil-lymphocyte ratio, pain perception, and disease activity score may serve as important predictive markers for sustained remission in rheumatoid arthritis. AB - The implementation of new treatment strategies based on current recommendations has enabled a greater number of patients with rheumatoid arthritis (RA) to achieve remission. However, there are no definite predictors of sustained remission. Moreover, the absence of clear consensus on the time of withdrawal or reduction of treatment further adds to the treatment burden. This pilot study was intended to evaluate the prognostic potential of various RA-related parameters. All the enrolled subjects (n=124) were clinically evaluated on the basis of various parameters including age, gender, duration of illness before the initiation of disease-modifying anti-rheumatic drugs, tender and swollen joints (28 joints), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin percentage, lymphocyte count, total white-blood cell counts, and neutrophil to lymphocyte ratio (NLR). Student's t-test and discriminant function analysis were performed. The specificity of all parameters and their best possible cut-off to predict relapse were calculated using the receiver operating characteristic (ROC) analysis. A significant difference in terms of pain perception, NLR, tendency to have a significant tender joint count and absolute lymphocyte counts was identified between the patients in sustained remission and those in relapse. The ROC analysis indicated that NLR was consistent in predicting remission. CRP, ESR, and/or disease activity score may not be very effective in differentiating patients with sustainable remission/low disease activity. NLR along with patient's perception of pain may assist in predicting sustained remission. PMID- 26876191 TI - Erasmus syndrome in a marble worker. AB - Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynaud's phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT) detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage) excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient. PMID- 26876192 TI - Rheumatoid trigger wrist. PMID- 26876193 TI - Myasthenia gravis due to hydroxychloroquine. PMID- 26876194 TI - Ultrafast Optical Microscopy of Single Monolayer Molybdenum Disulfide Flakes. AB - We have performed ultrafast optical microscopy on single flakes of atomically thin CVD-grown molybdenum disulfide, using non-degenerate femtosecond pump-probe spectroscopy to excite and probe carriers above and below the indirect and direct band gaps. These measurements reveal the influence of layer thickness on carrier dynamics when probing near the band gap. Furthermore, fluence-dependent measurements indicate that carrier relaxation is primarily influenced by surface related defect and trap states after above-bandgap photoexcitation. The ability to probe femtosecond carrier dynamics in individual flakes can thus give much insight into light-matter interactions in these two-dimensional nanosystems. PMID- 26876195 TI - Lessons from Domestication: Targeting Cis-Regulatory Elements for Crop Improvement. AB - Domestication of wild plant species has provided us with crops that serve our human nutritional needs. Advanced DNA sequencing has propelled the unveiling of underlying genetic changes associated with domestication. Interestingly, many changes reside in cis-regulatory elements (CREs) that control the expression of an unmodified coding sequence. Sequence variation in CREs can impact gene expression levels, but also developmental timing and tissue specificity of expression. When genes are involved in multiple pathways or active in several organs and developmental stages CRE modifications are favored in contrast to mutations in coding regions, due to the lack of detrimental pleiotropic effects. Therefore, learning from domestication, we propose that CREs are interesting targets for genome editing to create new alleles for plant breeding. PMID- 26876196 TI - HPV16 oncogene expression levels during early cervical carcinogenesis are determined by the balance of epigenetic chromatin modifications at the integrated virus genome. AB - In cervical squamous cell carcinomas, high-risk human papillomavirus (HRHPV) DNA is usually integrated into host chromosomes. Multiple integration events are thought to be present within the cells of a polyclonal premalignant lesion and the features that underpin clonal selection of one particular integrant remain poorly understood. We previously used the W12 model system to generate a panel of cervical keratinocyte clones, derived from cells of a low-grade premalignant lesion naturally infected with the major HRHPV type, HPV16. The cells were isolated regardless of their selective advantage and differed only by the site of HPV16 integration into the host genome. We used this resource to test the hypothesis that levels of HPV16 E6/E7 oncogene expression in premalignant cells are regulated epigenetically. We performed a comprehensive analysis of the epigenetic landscape of the integrated HPV16 DNA in selected clones, in which levels of virus oncogene expression per DNA template varied ~6.6-fold. Across the cells examined, higher levels of virus expression per template were associated with more open chromatin at the HPV16 long control region, together with greater loading of chromatin remodelling enzymes and lower nucleosome occupancy. There were higher levels of histone post-translational modification hallmarks of transcriptionally active chromatin and lower levels of repressive hallmarks. There was greater abundance of the active/elongating form of the RNA polymerase II enzyme (RNAPII-Ser2P), together with CDK9, the component of positive transcription elongation factor b complex responsible for Ser2 phosphorylation. The changes observed were functionally significant, as cells with higher HPV16 expression per template showed greater sensitivity to depletion and/or inhibition of histone acetyltransferases and CDK9 and less sensitivity to histone deacetylase inhibition. We conclude that virus gene expression per template following HPV16 integration is determined through multiple layers of epigenetic regulation, which are likely to contribute to selection of individual cells during cervical carcinogenesis. PMID- 26876197 TI - Heterozygous p53(V172F) mutation in cisplatin-resistant human tumor cells promotes MDM4 recruitment and decreases stability and transactivity of p53. AB - Cisplatin is an important antitumor agent, but its clinical utility is often limited by multifactorial mechanism of resistance. Loss of tumor suppressor p53 function is a major mechanism that is affected by either mutation in the DNA binding domain or dysregulation by overexpression of p53 inhibitors MDM2 and MDM4, which destabilize p53 by increasing its proteosomal degradation. In the present study, cisplatin-resistant 2780CP/Cl-16 ovarian tumor cells expressed a heterozygous, temperature-sensitive p53(V172F) mutation, which reduced p53 half life by two- to threefold compared with homozygous wild-type (wt) p53 in parental A2780 cells. Although reduced p53 stability in 2780CP/Cl-16 cells was associated with moderate cellular overexpression of MDM2 or MDM4 (<1.5-fold), their binding to p53 was substantially enhanced (five- to eightfold). The analogous cisplatin resistant 2780CP/Cl-24 cells, which express loss of p53 heterozygosity, retained the p53(V172F) mutation and high p53-MDM4 binding, but demonstrated lower p53 bound MDM2 that was associated with reduced p53 ubiquitination and enhanced p53 stability. The inference that p53 was unstable as a heteromeric p53(wt)/p53(V172F) complex was confirmed in 2780CP/Cl-24 cells transfected with wt p53 or multimer-inhibiting p53(L344P) mutant, and further supported by normalization of p53 stability in both resistant cell lines grown at the permissive temperature of 32.5 degrees C. Surprisingly, in 2780CP/Cl-16 and 2780CP/Cl-24 models, cisplatin-induced transactivity of p53 was attenuated at 37 degrees C, and this correlated with cisplatin resistance. However, downregulation of MDM2 or MDM4 by small interfering RNA in either resistant cell line induced p53 and restored p21 transactivation at 37 degrees C, as did cisplatin-induced DNA damage at 32.5 degrees C that coincided with reduced p53-MDM4 binding and cisplatin resistance. These results demonstrate that cisplatin-mediated p53(V172F) mutation regulates p53 stability at the normothermic temperature, but it is the increased recruitment of MDM4 by the homomeric or heteromeric mutant p53(V172F) complex that inhibits p53-dependent transactivation. This represents a novel cellular mechanism of p53 inhibition, and, thereby, induction of cisplatin resistance. PMID- 26876198 TI - CDCP1 cleavage is necessary for homodimerization-induced migration of triple negative breast cancer. AB - Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks the estrogen, progesterone and HER2 receptors and is resistant to targeted and hormone therapies. TNBCs express high levels of the transmembrane glycoprotein, complement C1r/C1s, Uegf, Bmp1 (CUB)-domain containing protein 1 (CDCP1), which has been correlated with the aggressiveness and poor prognosis of multiple carcinomas. Full-length CDCP1 (flCDCP1) can be proteolytically cleaved, resulting in a cleaved membrane-bound isoform (cCDCP1). CDCP1 is phosphorylated by Src family kinases in its full-length and cleaved states, which is important for its pro-metastatic signaling. We observed that cCDCP1, compared with flCDCP1, induced a dramatic increase in phosphorylation of the migration-associated proteins: PKCdelta, ERK1/2 and p38 mitogen-activated protein kinase in HEK 293T. In addition, only cCDCP1 induced migration of HEK 293T cells and rescued migration of the TNBC cell lines expressing short hairpin RNA against CDCP1. Importantly, we found that only cCDCP1 is capable of dimerization, which can be blocked by expression of the extracellular portion of cCDCP1 (ECC), indicating that dimerization occurs through CDCP1's ectodomain. We found that ECC inhibited phosphorylation of PKCdelta and migration of TNBC cells in two-dimensional culture. Furthermore, ECC decreased cell invasiveness, inhibited proliferation and stimulated apoptosis of TNBC cells in three dimensional culture, indicating that the cCDCP1 dimer is an important contributor to TNBC aggressiveness. These studies have important implications for the development of a therapeutic to block CDCP1 activity and TNBC metastasis. PMID- 26876199 TI - Disruption of insulin receptor function inhibits proliferation in endocrine resistant breast cancer cells. AB - The insulin-like growth factor (IGF) system is a well-studied growth regulatory pathway implicated in breast cancer biology. Clinical trials testing monoclonal antibodies directed against the type I IGF receptor (IGF1R) in combination with estrogen receptor-alpha (ER) targeting have been completed, but failed to show benefits in patients with endocrine-resistant tumors compared to ER targeting alone. We have previously shown that the closely related insulin receptor (InsR) is expressed in tamoxifen-resistant (TamR) breast cancer cells. Here we examined if inhibition of InsR affected TamR breast cancer cells. InsR function was inhibited by three different mechanisms: InsR short hairpin RNA, a small InsR blocking peptide, S961 and an InsR monoclonal antibody (mAb). Suppression of InsR function by these methods in TamR cells successfully blocked insulin-mediated signaling, monolayer proliferation, cell cycle progression and anchorage independent growth. This strategy was not effective in parental cells likely because of the presence of IGFR /InsR hybrid receptors. Downregulation of IGF1R in conjunction with InsR inhibition was more effective in blocking IGF- and insulin-mediated signaling and growth in parental cells compared with single receptor targeting alone. Our findings show TamR cells were stimulated by InsR and were not sensitive to IGF1R inhibition, whereas in tamoxifen-sensitive parental cancer cells, the presence of both receptors, especially hybrid receptors, allowed cross-reactivity of ligand-mediated activation and growth. To suppress the IGF system, targeting of both IGF1R and InsR is optimal in endocrine sensitive and -resistant breast cancer. PMID- 26876200 TI - Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway. AB - In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal. These breast tissue specimens have been profiled for their microRNA (miR) expression, in search of differentially expressed miR among patients treated or not with IORT. Our results demonstrate that IORT elicits effects that go beyond the direct killing of residual tumor cells. IORT altered the wound response, inducing the expression of miR-223 in the peri-tumoral breast tissue. miR-223 downregulated the local expression of epidermal growth factor (EGF), leading to decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EGF-EGFR autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. Accordingly, both RT-induced miR-223 and peri-operative inhibition of EGFR efficiently prevented BC cell growth and reduced recurrence formation in mouse models of BC. Our study uncovers unknown effects of RT delivered on a wounded tissue and prompts to the use of anti-EGFR treatments, in a peri operative treatment schedule, aimed to timely treat BC patients and restrain recurrence formation. PMID- 26876201 TI - Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression. AB - Deregulated Notch signaling is associated with T-cell Acute Lymphoblastic Leukemia (T-ALL) development and progression. Increasing evidence reveals that Notch pathway has an important role in the invasion ability of tumor cells, including leukemia, although the underlying molecular mechanisms remain mostly unclear. Here, we show that Notch3 is a novel target protein of the prolyl isomerase Pin1, which is able to regulate Notch3 protein processing and to stabilize the cleaved product, leading to the increased expression of the intracellular domain (N3IC), finally enhancing Notch3-dependent invasiveness properties. We demonstrate that the combined inhibition of Notch3 and Pin1 in the Notch3-overexpressing human leukemic TALL-1 cells reduces their high invasive potential, by decreasing the expression of the matrix metalloprotease MMP9. Consistently, Pin1 depletion in a mouse model of Notch3-induced T-ALL, by reducing N3IC expression and signaling, impairs the expansion/invasiveness of CD4(+)CD8(+) DP cells in peripheral lymphoid and non-lymphoid organs. Notably, in in silico gene expression analysis of human T-ALL samples we observed a significant correlation between Pin1 and Notch3 expression levels, which may further suggest a key role of the newly identified Notch3-Pin1 axis in T-ALL aggressiveness and progression. Thus, combined suppression of Pin1 and Notch3 proteins may be exploited as an additional target therapy for T-ALL. PMID- 26876202 TI - Secretory leukocyte protease inhibitor is a survival and proliferation factor for castration-resistant prostate cancer. AB - Androgen receptor (AR)-mediated gene expression continues to have a critical role in promoting castration-resistant prostate cancer (CRPC) survival and growth even after androgen deprivation therapy. AR cistrome analyses in CRPC cells have identified a large number of AR target genes involved in proliferative and cell cycle-related functions, and hold promise for development of novel therapeutic approaches for CRPC. However, there is little understanding of how these genes function in vivo and what the clinical implications are. We previously reported that secretory leukocyte peptidase inhibitor (SLPI) is regulated by the AR in a ligand-independent manner in CRPC cells and required for CRPC cell proliferation under androgen-deprived conditions. SLPI is a secreted serine protease inhibitor, which is overexpressed in a number of cancers, including lung, breast and ovarian cancer, and involved in tumor progression. However, the oncogenic potential of SLPI in prostate cancer remains unknown. Here we provide the first evidence that SLPI is upregulated in a subset of CRPC cell lines and CRPC patient tumors. In addition, serum SLPI levels are significantly elevated in metastatic CRPC patients compared with hormone naive patients, raising the possibility that this could serve as a biomarker. We demonstrated that SLPI expression has functional significance, as it promotes CRPC cell survival and growth after androgen withdrawal in vivo and in vitro. Last, we demonstrated that the oncogenic effect of SLPI may be due to protection of growth factor progranulin from enzymatic cleavage or suppression of CRPC cell apoptosis independent of anti-protease activity of SLPI. These findings implicate SLPI as a potential biomarker of resistance to AR inhibition and therapeutic target for CRPC treatment. PMID- 26876203 TI - Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/beta-catenin pathway. AB - The Wnt/beta-catenin pathway has important roles in chemoresistance and multidrug resistance 1 (MDR1) expression in some cancers, but its involvement in breast cancer and the underlying molecular mechanism are undefined. In this study, we demonstrated that the Wnt/beta-catenin pathway is activated in chemoresistant breast cancer cells. Using a Wnt pathway-specific PCR array screening assay, we detected that Pygo2, a newly identified Wnt/beta-catenin pathway component, was the most upregulated gene in the resistant cells. Additional experiments indicated that Pygo2 activated MDR1 expression in the resistant cells via the Wnt/beta-catenin pathway. Moreover, the inhibition of Pygo2 expression restored the chemotherapeutic drug sensitivity of the resistant cells and reduced the breast cancer stem cell population in these cells in response to chemotherapy. Importantly, these activities induced by Pygo2 were mediated by MDR1. We also determined the effect of Pygo2 on the sensitivity of breast tumors resistant to doxorubicin in a mouse model. Finally, RNA samples from 64 paired patient tumors (before and after chemotherapy) highly and significantly overexpressed Pygo2 and/or MDR1 after treatment, thus underlining a pivotal role for the Pygo2 mediated Wnt/beta-catenin pathway in the clinical chemoresistance of breast cancer. Our data represent the first implication of the Wnt/beta-catenin pathway in breast cancer chemoresistance and identify potential new targets to treat the recurrence of breast cancer. PMID- 26876204 TI - A novel KLF6-Rho GTPase axis regulates hepatocellular carcinoma cell migration and dissemination. AB - The presence of invasion into the extra-hepatic portion of the portal vein or the development of distant metastases renders hepatocellular carcinoma (HCC) patients ineligible for the only potential curative options for this malignancy-tumor resection or organ transplantation. Gene expression profiling of murine HCC cell lines identified KLF6 as a potential regulator of HCC cell migration. KLF6 knockdown increases cell migration, consistent with the correlation between decreased KLF6 mRNA levels and the presence of vascular invasion in human HCC. Concordantly, single-copy deletion of Klf6 in a HCC mouse model results in increased tumor formation, increased metastasis to the lungs and decreased survival, indicating that KLF6 suppresses both HCC development and metastasis. By combining gene expression profiling and chromatin immunoprecipitation coupled to deep sequencing, we identified novel transcriptional targets of KLF6 in HCC cells including VAV3, a known activator of the RAC1 small GTPase. Indeed, RAC1 activity is increased in KLF6-knockdown cells in a VAV3-dependent manner, and knockdown of either RAC1 or VAV3 impairs HCC cell migration. Together, our data demonstrate a novel function for KLF6 in constraining HCC dissemination through the regulation of a VAV3-RAC1 signaling axis. PMID- 26876205 TI - Upregulation of the oncoprotein SET determines poor clinical outcomes in hepatocellular carcinoma and shows therapeutic potential. AB - The SET protein is a potent inhibitor of protein phosphatase 2A (PP2A). Here, we report the oncogenic role of SET in hepatocarcinogenesis, clinical aggressiveness and anti-hepatocellular carcinoma (HCC) therapeutics. By analyzing samples obtained from 147 HCC patients, we found that SET overexpression was detected specifically in 30.6% HCC tumor samples, and was significantly associated with worse clinical features and high p-Akt expression in HCC tumors. Co-expression of SET and Akt predicted shorter post-operative recurrence-free survival in this cohort (P=0.045). Furthermore, SET was significantly associated with cell growth and hepatosphere formation. To elucidate the anti-HCC potential of targeting SET, we generated a novel SET antagonist, EMQA (N(4)-(3-ethynylphenyl)-6,7-dimethoxy N(2)-(4-phenoxyphenyl) quinazoline-2,4-diamine). EMQA enhanced PP2A activity via disrupting SET-PP2Ac (catalytic domain of PP2A) binding in HCC cells, which restored PP2A-mediated p-Akt downregulation and promoted HCC cell death. In HCC cells or recombinant proteins expressing the N- and C- truncated forms of SET, only the C-terminal SET was required for EMQA targeting. Furthermore, combining sorafenib and EMQA showed good synergism in inhibiting HCC survival. Our findings suggested the oncogenic role of SET and the adverse prognostic value of SET overexpression in HCC. This alteration defines a subgroup of HCC patients who could benefit from SET antagonists, such as EMQA. PMID- 26876206 TI - Cyclin G2 inhibits epithelial-to-mesenchymal transition by disrupting Wnt/beta catenin signaling. AB - Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecological malignancies owing to poor screening methods, non-specific symptoms and limited knowledge of the cellular targets that contribute to the disease. Cyclin G2 is an unconventional cyclin that acts to oppose cell cycle progression. Dysregulation of the cyclin G2 gene (CCNG2) in a variety of human cancers has been reported; however, the role of cyclin G2 in tumorigenesis remains unclear. In this study, we investigated the function of cyclin G2 in EOC. In vitro and in vivo studies using several EOC-derived tumor cell lines revealed that cyclin G2 inhibited cell proliferation, migration, invasion and spheroid formation, as well as tumor formation and invasion. By interrogating cDNA microarray data sets, we found that CCGN2 mRNA is reduced in several large cohorts of human ovarian carcinoma when compared with normal ovarian surface epithelium or borderline tumors of the ovary. Mechanistically, cyclin G2 was found to suppress epithelial to-mesenchymal transition (EMT), as demonstrated by the differential regulation of various EMT genes, such as Snail, Slug, vimentin and E-cadherin. Moreover, cyclin G2 potently suppressed the Wnt/beta-catenin signaling pathway by downregulating key Wnt components, namely LRP6, DVL2 and beta-catenin, which could be linked to inhibition of EMT. Taken together, our novel findings demonstrate that cyclin G2 has potent tumor-suppressive effects in EOCs by inhibiting EMT through attenuating Wnt/beta-catenin signaling. PMID- 26876207 TI - Loss of DAB2IP in RCC cells enhances their growth and resistance to mTOR-targeted therapies. AB - Targeted therapies using small-molecule inhibitors (SMIs) are commonly used in metastatic renal cell cancer (mRCC) patients; patients often develop drug resistance and eventually succumb to disease. Currently, understanding of mechanisms leading to SMIs resistance and any identifiable predictive marker(s) are still lacking. We discovered that DAB2IP, a novel Ras-GTPase-activating protein, was frequently epigenetically silenced in RCC, and DAB2IP loss was correlated with the overall survival of RCC patients. Loss of DAB2IP in RCC cells enhances their sensitivities to growth factor stimulation and resistances to SMI (such as mammalian target of rapamycin (mTOR) inhibitors). Mechanistically, loss of DAB2IP results in the activation of extracellular signal-regulated kinase/RSK1 and phosphoinositide-3 kinase/mTOR pathway, which synergizes the induction of hypoxia-inducible factor (HIF)-2alpha expression. Consequently, elevated HIF 2alpha suppresses p21/WAF1 expression that is associated with resistance to mTOR inhibitors. Thus combinatorial targeting both pathways resulted in a synergistic tumor inhibition. DAB2IP appears to be a new prognostic/predictive marker for mRCC patients, and its function provides a new insight into the molecular mechanisms of drug resistance to mTOR inhibitors, which also can be used to develop new strategies to overcome drug-resistant mRCC. PMID- 26876208 TI - Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression. AB - Alterations in long non-coding RNAs (lncRNAs) are associated with human carcinogenesis. One group of lncRNAs, which are antisense in orientation to coding mRNAs (ASs), have been recently described in cancers but are poorly understood. We sought to identify ASs involved in human gastric cancer (GC) and to elucidate their mechanisms of action in carcinogenesis. We performed massively parallel RNA sequencing in GCs and matched normal tissues, as well as in GC derived and normal gastric epithelial cell lines. One AS, designated Homo sapiens keratin 7 (KRT7-AS), was selected due to its marked upregulation and concordant expression with its cognate sense counterpart, KRT7, in GC tissues and cell lines. KRT7-AS formed an RNA-RNA hybrid with KRT7 and controlled KRT7 expression at both the mRNA and the post-transcriptional levels. Moreover, forced overexpression of the KRT7-overlapping region (OL) of KRT7-AS (but not its non KRT7-OL portions) increased keratin 7 protein levels in cells. Finally, forced overexpression of full-length KRT7-AS or OL KRT7-AS (but not its non-KRT7-OL regions) promoted GC cell proliferation and migration. We conclude that lncRNA KRT7-AS promotes GC, at least in part, by increasing KRT7 expression. PMID- 26876209 TI - Loss of MLCK leads to disruption of cell-cell adhesion and invasive behavior of breast epithelial cells via increased expression of EGFR and ERK/JNK signaling. AB - Myosin light chain kinase (MLCK) expression is downregulated in breast cancer, including invasive ductal carcinoma compared with ductal breast carcinoma in situ and metastatic breast tumors. However, little is known about how loss of MLCK expression contributes to tumor progression. MLCK is a component of the actin cytoskeleton and its known role is the phosphorylation of the regulatory light chain of myosin II. To gain insights into the role of MLCK in breast cancer, we perturbed its function using small interfering RNA (siRNA) or pharmacological inhibition in untransformed breast epithelial cells (MCF10A). Loss of MLCK by siRNAs led to increased cell migration and invasion, disruption of cell-cell adhesions and enhanced formation of focal adhesions at the leading edge of migratory cells. In addition, downregulation of MLCK cooperated with HER2 in MCF10A cells to promote cell migration and invasion and low levels of MLCK is associated with a poor prognosis in HER2-positive breast cancer patients. Associated with these altered migratory behaviors were increased expression of epidermal growth factor receptor and activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase signaling pathways in MLCK downregulated MCF10A cells. By contrast, inhibition of the kinase function of MLCK using pharmacological agents inhibited cell migration and invasion, and did not affect cellular adhesions. Our results show that loss of MLCK contributes to the migratory properties of epithelial cells resulting from changes in cell-cell and cell-matrix adhesions, and increased epidermal growth factor receptor signaling. These findings suggest that decreased expression of MLCK may have a critical role during tumor progression by facilitating the metastatic potential of tumor cells. PMID- 26876210 TI - Rad54 and Mus81 cooperation promotes DNA damage repair and restrains chromosome missegregation. AB - Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA-damaging agents, defects on both the homologous recombination and non-homologous DNA end joining repair pathways and reduced fertility. We also observed that while Mus81 deficiency diminished the cleavage of common fragile sites, very strikingly, Rad54 loss impaired this cleavage to even a greater extent. The inefficient repair of DNA double-strand breaks (DSBs) in Rad54(-/-)Mus81(-/-) cells was accompanied by elevated levels of chromosome missegregation and cell death. Perhaps as a consequence, tumor incidence in Rad54(-/-)Mus81(-/-) mice remained comparable to that in Mus81(-/-) mice. Our study highlights the importance of the cooperation between Rad54 and Mus81 for mediating DNA DSB repair and restraining chromosome missegregation. PMID- 26876211 TI - Extracellular lumican augments cytotoxicity of chemotherapy in pancreatic ductal adenocarcinoma cells via autophagy inhibition. AB - Lumican, an extracellular matrix proteoglycan overexpressed by pancreatic stellate cells (PSCs) and pancreatic ductal adenocarcinoma cells (PDACs), drives the formation of a tumor-specific microenvironment. We recently showed that extracellular lumican inhibits pancreatic cancer cell growth and is associated with prolonged survival after surgery. Here we investigated the role of extracellular lumican in chemotherapy-mediated cancer therapy. Lumican secretion was increased by chemotherapeutic agents in PDAC, and especially in PSCs, and appeared to be linked to the extent of cells' response to chemotherapy-induced growth inhibition. In multiple PDAC models, including cell lines, patient-derived xenografts and lumican knockout mice, lumican significantly increased antitumor effect of chemotherapy. This effect was associated with DNA damage, apoptosis and inhibition of cell viability, glucose consumption, lactate production and vascular endothelial growth factor secretion. In PDAC cells, chemotherapeutic agents triggered autophagosome formation and increased LC3 expression through the reactive oxygen species-mediated AMP-activated kinase (AMPK) signaling pathway. Inhibition of gemcitabine-induced autophagy in cancer cells by treatment with AMPK inhibitor compound C, lysosomal inhibitor chloroquine or autophagy inhibitor 3MA enhanced gemcitabine-induced apoptosis, suggesting that autophagy is a protective cellular response to gemcitabine treatment. Importantly, lumican dramatically decreased AMPK activity, inhibiting chemotherapy-induced autophagy in both in vitro and in vivo PDAC models. Co-treatment of PDAC cells with lumican and gemcitabine increased mitochondrial damage, reactive oxygen species (ROS) production and cytochrome c release, indicating that lumican-induced disruption of mitochondrial function may be the mechanism of sensitization to gemcitabine. Together, our findings demonstrate that extracellular lumican augments cytotoxicity of chemotherapy in PDAC cells through inhibition of chemotherapeutic agent-induced autophagy. PMID- 26876212 TI - Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFbeta signaling. AB - Head and neck squamous cell carcinoma (HNSCC) patients have a poor prognosis, with invasion and metastasis as major causes of mortality. The phosphatidylinositol 3-kinase (PI3K) pathway regulates a wide range of cellular processes crucial for tumorigenesis, and PIK3CA amplification and mutation are among the most common genetic alterations in human HNSCC. Compared with the well documented roles of the PI3K pathway in cell growth and survival, the roles of the PI3K pathway in tumor invasion and metastasis have not been well delineated. We generated a PIK3CA genetically engineered mouse model (PIK3CA-GEMM) in which wild-type PIK3CA is overexpressed in head and neck epithelium. Although PIK3CA overexpression alone was not sufficient to initiate HNSCC formation, it significantly increased tumor susceptibility in an oral carcinogenesis mouse model. PIK3CA overexpression in mouse oral epithelium increased tumor invasiveness and metastasis by increasing epithelial-mesenchymal transition and by enriching a cancer stem cell phenotype in tumor epithelial cells. In addition to these epithelial alterations, we also observed marked inflammation in tumor stroma. AKT is a central signaling mediator of the PI3K pathway. However, molecular analysis suggested that progression of PIK3CA-driven HNSCC is facilitated by 3-phosphoinositide-dependent protein kinase (PDK1) and enhanced transforming growth factor beta (TGFbeta) signaling rather than by AKT. Examination of human HNSCC clinical samples revealed that both PIK3CA and PDK1 protein levels correlated with tumor progression, highlighting the significance of this pathway. In summary, our results offer significant insight into how PIK3CA overexpression drives HNSCC invasion and metastasis, providing a rationale for targeting PI3K/PDK1 and TGFbeta signaling in advanced HNSCC patients with PIK3CA amplification. PMID- 26876213 TI - EGFR-targeted mAb therapy modulates autophagy in head and neck squamous cell carcinoma through NLRX1-TUFM protein complex. AB - Epidermal growth factor receptor (EGFR)-targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients frequently results in tumor resistance to treatment. Autophagy is an emerging underlying resistance mechanism, however, the molecular autophagy machinery in HNSCC cells and potential biomarkers of patient response to EGFR-targeted therapy remain insufficiently characterized. Here we show that the EGFR blocking with cetuximab leads to varied autophagic responses, which modulate cancer cell susceptibility to EGFR inhibition. Inhibition of autophagy sensitizes HNSCC cells to EGFR blockade. Importantly, we identify a novel signaling hub centering on the NLRX1 (nucleotide-binding, lots of leucine-rich repeats-containing protein member X1)-TUFM (Tu translation elongation factor mitochondrial) protein complex, promoting autophagic flux. Defects in the expression of either NLRX1 or TUFM result in compromised autophagy when treated with EGFR inhibitors. As a previously undefined autophagy-promoting mechanism, we found that TUFM serves as a novel anchorage site, recruiting Beclin 1 to mitochondria, promoting its polyubiquitination, and interfering with its interaction with Rubicon. This protein complex is also essential for endoplasmic reticulum stress signaling induction, possibly as an additional mechanism to promote autophagy. Utilizing tumor specimens from a novel neoadjuvant clinical trial, we show that increased expression of the autophagy adaptor protein, SQSTM1/p62, is associated with poor response to cetuximab therapy. These findings expand our understanding of the components involved in HNSCC autophagy machinery that responds to EGFR inhibitors, and suggest potential combinatorial approaches to enhance its therapeutic efficacy. PMID- 26876217 TI - Construction of enantioenriched polysubstituted hexahydropyridazines via a sequential multicatalytic process merging palladium catalysis and aminocatalysis. AB - An efficient multicatalytic strategy for the construction of nitrogen-containing heterocycles has been reported. The powerful combination of organic and metal catalysis in a single vessel allowed the formation of enantioenriched polysubstituted cyclic 6-membered hydrazines bearing a quaternary stereocenter in good yields and selectivities. PMID- 26876215 TI - Microtubule-associated protein 4 is an important regulator of cell invasion/migration and a potential therapeutic target in esophageal squamous cell carcinoma. AB - Cell invasion and migration significantly contribute to tumor metastasis. Microtubule-associated protein 4 (MAP4) protein is one member of microtubule associate proteins family. It is responsible for stabilization of microtubules by modulation of microtubule dynamics. However, there is little information about the involvement of MAP4 in human cancer. Here we show that MAP4 serves as a regulator of invasion and migration in esophageal squamous cancer cells. By activating the ERK-c-Jun-vascular endothelial growth factor A signaling pathway, MAP4 promotes cell invasion and migration in vitro, tumor growth and metastasis in mouse models. Immunohistochemical staining of operative tissues indicated that MAP4 expression was associated with tumor stage, lymph node metastasis and shorter survival of the patients with esophageal squamous cell carcinoma (ESCC). Multivariate Cox regression analysis showed that MAP4 is an independent prognostic indicator. In the serial sections of ESCC tissues, there was a positive correlation between MAP4 and vascular endothelial growth factor A expression. Notably, an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4 expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease. PMID- 26876214 TI - STRIPAK complexes in cell signaling and cancer. AB - Striatin-interacting phosphatase and kinase (STRIPAK) complexes are striatin centered multicomponent supramolecular structures containing both kinases and phosphatases. STRIPAK complexes are evolutionarily conserved and have critical roles in protein (de)phosphorylation. Recent studies indicate that STRIPAK complexes are emerging mediators and regulators of multiple vital signaling pathways including Hippo, MAPK (mitogen-activated protein kinase), nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are extensively involved in a variety of fundamental biological processes ranging from cell growth, differentiation, proliferation and apoptosis to metabolism, immune regulation and tumorigenesis. Growing evidence correlates dysregulation of STRIPAK complexes with human diseases including cancer. In this review, we summarize the current understanding of the assembly and functions of STRIPAK complexes, with a special focus on cell signaling and cancer. PMID- 26876216 TI - HGF/Met and FOXM1 form a positive feedback loop and render pancreatic cancer cells resistance to Met inhibition and aggressive phenotypes. AB - Hepatocyte growth factor (HGF)/Met signaling has critical roles in pancreatic ductal adenocarcinoma (PDA) development and progression and is considered a potential therapeutic target for this disease. However, the mechanism of aberrant activation of HGF/Met signaling and resistance to Met inhibition in PDA remains unclear. The mechanistic role of cross talk between Forkhead box M1 (FOXM1) and HGF/Met signaling in promotion of PDA growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of our experimental and mechanistic findings were validated using human PDA tissues. Met was markedly overexpressed in both PDA cell lines and pancreatic tumor specimens, and the expression of Met correlated directly with that of FOXM1 in human tumor specimens. Mechanistically, FOXM1 bound to the promoter region of the Met gene and transcriptionally increased the expression of Met. Increased expression of FOXM1 enhanced the activation of HGF/Met signaling and its downstream pathways, including retrovirus-associated DNA sequences/extracellular signal-regulated kinase 1/2, phosphoinositide 3-kinase/AKT and signal transducer and activator of transcription 3. Furthermore, activation of HGF/Met signaling increased the expression and transcriptional activity of FOXM1, and the cross talk between FOXM1 and HGF/Met signaling promoted PDA growth and resistance to Met inhibition. Collectively, our findings identified a positive feedback loop formed by FOXM1 and HGF/Met and revealed that this loop is a potentially effective therapeutic target for PDA. PMID- 26876218 TI - Promising Therapies for Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) is the most frequent progressive neurodegenerative disease. Cholinergic dysfunction is one of the major pathological alteration, although depletion of cholinergic neurons is caused by the well-established toxicity of the beta-amyloid plaques and neurofibrillary tangles. Cholinergic dysfunctions are consequences of the decrease in acetylcholine synthesis and release, and altered function of muscarinic and nicotinic cholinergic receptors. In addition, a direct correlation between cholinergic alteration, amyloidbeta production and tau phosphorylation, two main AD-pathology hallmarks, has been identified. METHODS: In the present review we focused our discussion on the identification of new allosteric or bitopic ligands able to modulate the cholinergic receptor activity. Moreover drug delivery methodology (nanoparticeles, liposomes, etc.) that might contribute to drive the drug in the brain, reducing their toxicity and potential side effects have been also discussed. RESULTS: Many drugs are currently in use for AD (e.g. donepezil, rivastigmine etc.) and several of those in development such as muscarininc and nicotinic agonists, target specifically the cholinergic system; the main mechanism aims to rescue the cholinergic dysfunction, to reduce neurotoxic protein accumulation and improve the cholinergic impairments responsible of the cognitive deficits. Promising approaches aim to either improve drug delivery into the brain or develope new compounds targeting known or new molecular pathways. Nanoparticles and liposomes are also described as new nanotechnology tools that overcome traditional routes of administration, with a particular focus on their employment for compounddelivery that targets the cholinergic system. Ultimately, a new fields of research is emerging as the use of induced pluripotent stem cells, a technology that allows to obtain cells directly from the patients that can be propagated indefinetely and differentiated into the susceptible neuronal subtypes. This may significantly contribute to improve the understanding of AD pathological processes and enhance current AD pharmacology beyond the cholinergic dysfunction. CONCLUSION: From the topics discussed in the present review, emerges that the combination between pharmacological studies and nanotechnological approaches for drug delivery and the identification of new specific models may largely enhance and improve the therapeutic strategies for different neurological disease including AD. PMID- 26876219 TI - Relationship of bovine TNF-alpha gene polymorphisms with the risk of bovine tuberculosis in Holstein cattle. AB - Many studies suggest significant genetic variation in the resistance of cattle and humans to infection with Mycobacterium bovis (M. bovis), the causative agent of zoonotic tuberculosis. TNF-alpha promotes inflammation and induces apoptosis in response to mycobacterial infection. The aim of the present study was to investigate the influence of single nucleotide polymorphisms of the TNF-alpha gene on bovine tuberculosis (bTB) susceptibility. We genotyped the TNF-alpha gene in 74 bTB-infected Holstein cows and 90 healthy control animals. The influence in the exon 3 region of TNF-alpha polymorphisms on bTB susceptibility was subsequently investigated by association analysis. Our finding demonstrated that the g.27534932A>C polymorphism of the TNF-alpha is associated with bTB in Holstein cattle. The susceptibility of cattle with the g.27534932A>C genotype compared with the CC genotype was 4.11-fold (95% CI, 1.27-13.36; P=0.02) higher. The g.27534932A>C polymorphism located in exon 3 of the TNF-alpha gene, and the functional consequence was missense. The deduced amino acid sequence for the protein product revealed an arginine to serine conversion at position 159, which may affect initiation of protein synthesis and disrupt normal TNF-alpha function that protects animals against mycobacterial infection. A significant association was observed with the A allele as a risk factor for bTB susceptibility (OR, 3.84; 95% CI, 1.21-12.17; P=0.02). In conclusion, this is the first report showing that the g.27534932A>C polymorphism may contribute to TNF-alpha-mediated bTB susceptibility. PMID- 26876220 TI - High genetic diversity and frequent genetic reassortment of avian influenza A(H9N2) viruses along the East Asian-Australian migratory flyway. AB - To understand the molecular epidemiology and evolution of avian influenza viruses (AIV) along the East Asian-Australian migration flyway, we collected faecal samples (n=2859) between November 2014 and March 2015 from poultry, environmental sources and wild birds in Dongying, Shandong province and Yancheng, Jiangsu province in eastern China. The presence of AIV RNA was evaluated by real-time PCR and the positivity rate ranged from 0 to 29.3%. In both Dongying and Yancheng, samples collected from live poultry markets had the highest positivity rate for AIV RNA. AIV whole genomes were generated and phylogenetically analysed. Our results demonstrate that most of the viruses belonged to the H9N2 subtype, and could be classified into nine novel genotypes based on the phylogenetic analysis of the eight gene segments of the AIV genomes. This revealed a high genetic diversity of H9N2 in this region and suggested that they might have undergone frequent genetic reassortment. In addition, the internal genes (PB2, etc.) of two viruses from wild birds and several viruses from poultry belonged to the same gene constellation, suggesting a potential inter-host transmission of AIV between wild birds and poultry in live markets along routes of migratory flyways. Our results highlight the high genetic diversity of AIV along the East Asian Australian migration flyway and the need for more extensive AIV surveillance in eastern China. PMID- 26876221 TI - Complete genome sequence of mumps viruses isolated from patients with parotitis, pancreatitis and encephalitis in India. AB - Limited information is available regarding epidemiology of mumps in India. Mumps vaccine is not included in the Universal Immunization Program of India. The complete genome sequences of Indian mumps virus (MuV) isolates are not available, hence this study was performed. Five isolates from bilateral parotitis and pancreatitis patients from Maharashtra, a MuV isolate from unilateral parotitis patient from Tamil Nadu, and a MuV isolate from encephalitis patient from Uttar Pradesh were genotyped by the standard protocol of the World Health Organization and subsequently complete genomes were sequenced. Indian MuV genomes were compared with published MuV genomes, including reference genotypes and eight vaccine strains for the genetic differences. The SH gene analysis revealed that five MuV isolates belonged to genotype C and two belonged to genotype G strains. The percent nucleotide divergence (PND) was 1.1% amongst five MuV genotype C strains and 2.2% amongst two MuV genotype G strains. A comparison with widely used mumps Jeryl Lynn vaccine strain revealed that Indian mumps isolates had 54, 54, 53, 49, 49, 38, and 49 amino acid substitutions in Chennai-2012, Kushinagar 2013, Pune-2008, Osmanabad-2012a, Osmanabad-2012b, Pune-1986 and Pune-2012, respectively. This study reports the complete genome sequences of Indian MuV strains obtained in years 1986, 2008, 2012 and 2013 that may be useful for further studies in India and globally. PMID- 26876223 TI - Machine Learning Strategy for Accelerated Design of Polymer Dielectrics. AB - The ability to efficiently design new and advanced dielectric polymers is hampered by the lack of sufficient, reliable data on wide polymer chemical spaces, and the difficulty of generating such data given time and computational/experimental constraints. Here, we address the issue of accelerating polymer dielectrics design by extracting learning models from data generated by accurate state-of-the-art first principles computations for polymers occupying an important part of the chemical subspace. The polymers are 'fingerprinted' as simple, easily attainable numerical representations, which are mapped to the properties of interest using a machine learning algorithm to develop an on-demand property prediction model. Further, a genetic algorithm is utilised to optimise polymer constituent blocks in an evolutionary manner, thus directly leading to the design of polymers with given target properties. While this philosophy of learning to make instant predictions and design is demonstrated here for the example of polymer dielectrics, it is equally applicable to other classes of materials as well. PMID- 26876222 TI - Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis. AB - Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8(th) week post infection) and late (16(th) week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10(th) month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone. PMID- 26876224 TI - A randomized, double-blind, placebo controlled, parallel group, efficacy study of alpha BRAIN(r) administered orally. AB - OBJECTIVE: Alpha BRAIN(r) is a nootropic supplement that purports to enhance cognitive functioning in healthy adults. The goal of this study was to investigate the efficacy of this self-described cognitive enhancing nootropic on cognitive functioning in a group of healthy adults by utilizing a randomized, double blind, placebo-controlled design. METHODS: A total of 63-treatment naive individuals between 18 and 35 years of age completed the randomized, double blind, placebo controlled trial. All participants completed a 2-week placebo run in before receiving active product, Alpha BRAIN(r) or new placebo, for 6 weeks. Participants undertook a battery of neuropsychological tests at randomization and at study completion. Primary outcome measures included a battery of neuropsychological tests and measures of sleep. RESULTS: Compared with placebo, Alpha BRAIN(r) significantly improved on tasks of delayed verbal recall and executive functioning. Results also indicated significant time-by-group interaction in delayed verbal recall for the Alpha BRAIN(r) group. CONCLUSIONS: The use of Alpha BRAIN(r) for 6 weeks significantly improved recent verbal memory when compared with controls, in a group of healthy adults. While the outcome of the study is encouraging, this is the first randomized controlled trial of Alpha BRAIN(r), and the results merit further study. PMID- 26876226 TI - Oxygen Reduction Catalysis at a Dicobalt Center: The Relationship of Faradaic Efficiency to Overpotential. AB - The selective four electron, four proton, electrochemical reduction of O2 to H2O in the presence of a strong acid (TFA) is catalyzed at a dicobalt center. The faradaic efficiency of the oxygen reduction reaction (ORR) is furnished from a systematic electrochemical study by using rotating ring disk electrode (RRDE) methods over a wide potential range. We derive a thermodynamic cycle that gives access to the standard potential of O2 reduction to H2O in organic solvents, taking into account the presence of an exogenous proton donor. The difference in ORR selectivity for H2O vs H2O2 depends on the thermodynamic standard potential as dictated by the pKa of the proton donor. The model is general and rationalizes the faradaic efficiencies reported for many ORR catalytic systems. PMID- 26876225 TI - Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part I: Alternative Niacin Regimens. AB - Niacin was the first drug demonstrating lowered cholesterol prevents coronary heart disease (CHD) events, with two clinical CHD outcome studies establishing a cardioprotective niacin regimen: 1 g thrice daily with meals. Though cardioprotective, skin toxicity limits niacin's use, fostering several variations to improve tolerability. One of these, an extended-release (ER) alternative, proved immensely successful commercially, dominating clinical practice despite departing from the established regimen in several critical ways. Hence, improved tolerability may have come at the cost of diminished efficacy, posing a conundrum: Does it still help the population at risk for CHD to broaden a drug's acceptance by "watering it down"? This question is crucial at this stage now that the ER alternative failed to recapitulate the benefits of the established cardioprotective niacin regimen in two trials of the alternative approach: AIM HIGH and HPS2-THRIVE. Part I of this review discusses how vastly the ER alternative departs from the established cardioprotective regimen, why that is important physiologically, and how it may explain the findings of AIM-HIGH and HPS2-THRIVE. Given important gaps left by statin therapy, the established cardioprotective niacin regimen remains an important evidence-based therapy for the statin intolerant or statin averse. PMID- 26876227 TI - Retracted: Modern Concepts for Caries Tissue Removal. AB - "Modern Concepts for Caries Tissue Removal", by Falk Schwendicke The above article, published online on 15 February 2016 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.llll/jerd.12201), has been retracted by agreement between the author, Dr. Falk Schwendicke, the journal Editor-in-Chief, Dr. Harald O. Heymann, Associate Editor, Dr. Edward Swift and Wiley Periodicals, Inc. The retraction has been agreed as the article was published in advance of other companion work which should have had precedence. The article pages have been replaced by the Retraction Statement and the article condensed accordingly. Schwendicke, F. Swift, EJ. Modern concepts for caries tissue removal. Dent J Esthet Rest 2016; 28:1; DOI: 10.1111/jerd.12201. PMID- 26876228 TI - Protonation state of F420H2 in the prodrug-activating deazaflavin dependent nitroreductase (Ddn) from Mycobacterium tuberculosis. AB - The protonation state of the deazaflavin dependent nitroreductase (Ddn) enzyme bound cofactor F420 was investigated using UV-visible spectroscopy and computational simulations. The reduced cofactor F420H2 was determined to be present in its deprotonated state in the holoenzyme form. The mechanistic implications of these findings are discussed. PMID- 26876231 TI - Tracking the elusive history of diversification in plant-herbivorous insect parasitoid food webs: insights from figs and fig wasps. AB - The food webs consisting of plants, herbivorous insects and their insect parasitoids are a major component of terrestrial biodiversity. They play a central role in the functioning of all terrestrial ecosystems, and the number of species involved is mind-blowing (Nyman et al. 2015). Nevertheless, our understanding of the evolutionary and ecological determinants of their diversity is still in its infancy. In this issue of Molecular Ecology, Sutton et al. (2016) open a window into the comparative analysis of spatial genetic structuring in a set of comparable multitrophic models, involving highly species-specific interactions: figs and fig wasps. This is the first study to compare genetic structure using population genetics tools in a fig-pollinating wasp (Pleistodontes imperialis sp1) and its main parasitoid (Sycoscapter sp.A). The fig-pollinating wasp has a discontinuous spatial distribution that correlates with genetic differentiation, while the parasitoid bridges the discontinuity by parasitizing other pollinator species on the same host fig tree and presents basically no spatial genetic structure. The full implications of these results for our general understanding of plant-herbivorous insect-insect parasitoids diversification become apparent when envisioned within the framework of recent advances in fig and fig wasp biology. PMID- 26876232 TI - Aquatic biodiversity assessment for the lazy. AB - The world is covered in DNA. In any ecosystem, extracellular DNA fragments can be found that once formed the genomes of a variety of micro- and macroorganisms. A few years ago, it was proposed to use this environmental DNA (eDNA) as a source of information on local vertebrate biodiversity (Ficetola et al. 2008; Taberlet et al. 2012). This idea offered an elegant solution to take up the gauntlet of rapidly increasing monitoring needs. Coupled with barcoding efforts, it promised to be cost-efficient in many respects, for example man-hours and taxonomic expertise. Ecologists and conservation biologists with an interest in aquatic ecosystems have enthusiastically adopted and pioneered this new method, producing dozens of eDNA studies. Most of these studies have, however, focused on a single or a few aquatic species. In this issue of Molecular Ecology, Valentini et al. (2016) move the field a step further by demonstrating that metabarcoding approaches - which simultaneously target large groups of organisms such as amphibians or fish - can match and sometimes even outperform other inventory methods. PMID- 26876233 TI - One step ahead: a parasitoid disperses farther and forms a wider geographic population than its fig wasp host. AB - The structure of populations across landscapes influences the dynamics of their interactions with other species. Understanding the geographic structure of populations can thus shed light on the potential for interacting species to co evolve. Host-parasitoid interactions are widespread in nature and also represent a significant force in the evolution of plant-insect interactions. However, there have been few comparisons of population structure between an insect host and its parasitoid. We used microsatellite markers to analyse the population genetic structure of Pleistodontes imperialis sp. 1, a fig-pollinating wasp of Port Jackson fig (Ficus rubiginosa), and its main parasitoid, Sycoscapter sp. A, in eastern Australia. Besides exploring this host-parasitoid system, our study also constitutes, to our knowledge, the first study of population structure in a nonpollinating fig wasp species. We collected matched samples of pollinators and parasitoids at several sites in two regions separated by up to 2000 km. We found that pollinators occupying the two regions represent distinct populations, but, in contrast, parasitoids formed a single population across the wide geographic range sampled. We observed genetic isolation by distance for each species, but found consistently lower FST and RST values between sites for parasitoids compared with pollinators. Previous studies have indicated that pollinators of monoecious figs can disperse over very long distances, and we provide the first genetic evidence that their parasitoids may disperse as far, if not farther. The contrasting geographic population structures of host and parasitoid highlight the potential for geographic mosaics in this important symbiotic system. PMID- 26876235 TI - Uveal melanoma: An analysis of cellular features and comparison to monosomy 3 status. AB - BACKGROUND: Choroidal and ciliary body melanomas divide into two approximately equal groups. Local therapy cures one group while the other metastasizes and proves lethal. Monosomy 3 strongly associates with aggressive behavior. We analyzed a series of choroidal and ciliary body melanomas to describe the cellular features and to compare them to monosomy 3 status using the latter as a surrogate for survival. METHODS: One hundred eleven specimens met the study's inclusion criteria. Following ThinPrep processing, samples were analyzed for cellular features including: cell type, nuclear grade, tumor infiltrating lymphocytes, and the presence of necrosis and melanin. FISH analysis for monosomy 3 was performed on ThinPrep slides using a threshold of 20% monosomic cells per 200 melanoma cells. RESULTS: Seventy-two tumors (65%) had a mixed cell type while spindle cell type and epithelioid cell type occurred in 37 (33%) and 2 (1.8%), respectively. Seventy-five tumors (68%) had Grade 2 nuclear atypia. Monosomy 3 occurred in 57 tumors (51%). Significantly more tumors with Grade 3 nuclei had monosomy 3 (79% vs.43%, P = 0.002) and metastases (29% vs. 8%, P = 0.01). None of the 11 pure spindle cell tumors with Grade 1 nuclei metastasized or had monosomy 3. CONCLUSIONS: Uveal melanoma has a relatively consistent cellular appearance, characterized by a mixed cell pattern and no more than moderate nuclear atypia. This consistent appearance aids in the cellular diagnosis but limits prognostication using cellular features. Cellular features significantly associate with monosomy 3 status only in the minority of tumors at the extremes of the morphologic spectrum. PMID- 26876234 TI - Near-infrared imaging of secondary caries lesions around composite restorations at wavelengths from 1300-1700-nm. AB - BACKGROUND AND OBJECTIVES: Current clinical methods for diagnosing secondary caries are unreliable for identifying the early stages of decay around restorative materials. The objective of this study was to access the integrity of restoration margins in natural teeth using near-infrared (NIR) reflectance and transillumination images at wavelengths between 1300 and 1700-nm and to determine the optimal NIR wavelengths for discriminating composite materials from dental hard tissues. MATERIALS AND METHODS: Twelve composite margins (n=12) consisting of class I, II and V restorations were chosen from ten extracted teeth. The samples were imaged in vitro using NIR transillumination and reflectance, polarization sensitive optical coherence tomography (PS-OCT) and a high magnification digital microscope. Samples were serially sectioned into 200-MUm slices for histological analysis using polarized light microscopy (PLM) and transverse microradiography (TMR). Two independent examiners evaluated the presence of demineralization at the sample margin using visible detection with 10* magnification and NIR images presented digitally. Composite restorations were placed in sixteen sound teeth (n=16) and imaged at multiple NIR wavelengths ranging from lambda=1300 to 1700-nm using NIR transillumination. The image contrast was calculated between the composite and sound tooth structure. RESULTS: Intensity changes in NIR images at wavelengths ranging from 1300 to 1700-nm correlate with increased mineral loss measured using TMR. NIR reflectance and transillumination at wavelengths coincident with increased water absorption yielded significantly higher (P<0.001) contrast between sound enamel and adjacent demineralized enamel. In addition, NIR reflectance exhibited significantly higher (P<0.01) contrast between sound enamel and adjacent composite restorations than visible reflectance. SIGNIFICANCE: This study shows that NIR imaging is well suited for the rapid screening of secondary caries lesions. PMID- 26876237 TI - Investigating molecular interactions and surface morphology of wax-doped asphaltenes. AB - The nature and origin of bee-like microstructures (bees) in asphalt binders and their impact on asphalt oxidation have been the subject of extensive discussions in recent years. While several studies refer to the bees as solely surface features, some others consider them to be bulk microcrystalline components that are formed due to co-precipitation of wax and asphaltene molecules. In this study, we use a rigorous theoretical and experimental approach to investigate the interplay of asphalt components (mainly asphaltene and wax) and their impact on bee formation. In the theoretical section, quantum-mechanical calculations using density functional theory (DFT) are used to evaluate the strength of interactions between asphaltene unit sheets in the presence and absence of a wax component, as well as the mutual interactions between asphaltene molecules (monomers and dimers) and paraffin wax. The results of this section reveal that paraffin waxes not only do not reinforce the interaction between the asphaltene unit sheets, they destabilize asphaltene assembly and dimerization. AIM (Atom in Molecules) analysis shows the destabilizing effect of wax on asphaltene assembly as a reduction in the number of cage and bond critical points between asphaltenes. This destabilization effect among interacting systems (asphaltene-asphaltene and wax-asphaltene) does not support the hypothesis that interaction between paraffin waxes and non-wax components, such as asphaltene, is responsible for their co precipitation and bee formation. To further examine the effect of wax component on asphalt microstructure experimentally, we used atomic force microscopy (AFM) to study the surface morphology of an asphalt sample doped with 1% to 25% paraffin wax. In agreement with the conclusions drawn from the DFT approach, our experiments indicate that paraffin wax tends to crystallize separately and form lamellar paraffin wax crystal inclusions with 10 nm thickness. Moreover, the addition of 3% wax into asphalt results in a significant increase in surface roughness from 0.5 nm to 4.1 nm and an increase in bee wavelength from 651 nm to 1038 nm. PMID- 26876236 TI - The relationship between unhealthy food sales, socio-economic deprivation and childhood weight status: results of a cross-sectional study in England. AB - BACKGROUND: Recent increases in obesity prevalence have led to research into the neighbourhood food environment. Research suggests that proximity and density of food outlets around the home is associated with childhood obesity prevalence, however, the evidence is inconclusive, and associations between food outlet locations and diet are less clear. The purpose of this study is to assess area level associations between sales of unhealthy foods in supermarkets and weight status of children. METHODS: This study examined the association between weight status in children (4-5 year olds and 10-11 year olds) measured in the National Child Measurement Programme over three time points (2008/9, 2009/10, 2010/11) and annual sales of unhealthy foods (2012/3), as identified from a large supermarket chain. Geographical analysis was conducted to link store-based food sales for 537 stores with 6517 UK Census Areas. Unadjusted associations were examined with error-bar plots and linear regression was used to examine the relationship between the prevalence of overweight and obesity and sales of unhealthy food, while controlling for covariates known to predict weight status in children. RESULTS: A statistically significant relationship was identified between the sales of unhealthy foods and the prevalence of overweight and obese children in both age groups (p < 0.01). Of the covariates, area deprivation was positively associated with weight status (p < 0.001). Non-white population (%) was negatively associated (p < 0.001) with overweight and obesity among Reception children, but positively associated with the other weight statuses (p < 0.001). A higher proportion of children in the same age group were associated with statistically significantly lower overweight and obesity prevalence in Reception (p <0.01) but not Year 6 children. CONCLUSIONS: The study provides novel findings linking supermarket food sales with the weight status of children. Food sales in geographically referenced supermarkets are a valuable source of data for research into the factors that influence the weight of the surrounding population. Future research could identify factors that might modify food shopping in supermarkets and use of purchasing data could be an effective way to measure the impact of healthy eating campaigns on the weight status of children over time. PMID- 26876238 TI - Exercise therapy for trismus secondary to head and neck cancer: A systematic review. AB - BACKGROUND: Effects of exercise therapy for trismus secondary to head and neck cancer have not been reviewed systematically since 2004. METHODS: Four databases were searched. The quality of observational studies and randomized controlled trials was assessed. RESULTS: Two hundred eleven articles were found, 20 studies were included. A large variation in research methodology, stretching techniques, duration of stretch, and repetition of exercises was found. The overall quality was moderate. Five of the 8 preventive studies found that exercises during (chemo)radiotherapy could not prevent a reduction in mouth opening. In 4 therapeutic case studies, mouth opening increased between 17 and 24 mm. In 8 other therapeutic studies, mouth opening increased between -1.9 and 13.6 mm. No exercise therapy was clearly superior to the others. CONCLUSION: Changes in mouth opening ranged considerably and no stretching technique was superior to others regarding either prevention or treatment of trismus. Clinical guidelines cannot be given based on this systematic review. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 160-169, 2017. PMID- 26876239 TI - Erratum to: Effect of different culture media and deswelling agents on survival of human corneal endothelial and epithelial cells in vitro. PMID- 26876240 TI - Efficacy of combined orbital radiation and systemic steroids in the management of Graves' orbitopathy. AB - PURPOSE: To compare the efficacy and safety of combination therapy with orbital irradiation and systemic steroids versus steroid monotherapy in the management of active Graves' orbitopathy (GO). METHODS: The clinical charts of 127 patients with active inflammation due to GO who received intravenous steroid pulse therapy as a first-line treatment with or without orbital radiotherapy between 2010 and 2014 were reviewed. Patients were divided into two treatment groups: 1) combined orbital radiotherapy and steroid pulse therapy (SRT group) and 2) steroid pulse therapy only (ST group). Primary outcome measures included clinical activity score (CAS); NOSPECS classification; ocular motility impairment; and exophthalmos at 1, 3, 6, and 12 months after treatment. The secondary outcome measure was the change in orbital, extraocular muscle (EOM), and fat volume after treatment measured by orbit computed tomography. RESULTS: Sixty-eight patients were included in the SRT group, and 59 patients were in the ST group. In both treatments, CAS and NOSPECS were significantly reduced. In the comparison of the degree of change from baseline between the groups, the SRT group demonstrated more improvement in NOSPECS and scores of ocular motility. Orbital, EOM, and fat volume significantly decreased in the SRT group; however, only fat volume was reduced in the ST group. Compressive optic neuropathy after treatment developed in 0 % of the SRT group and 3.4 % (2/59) of the ST group. Reactivation of inflammation occurred in 11.8 % (8/68) of the SRT group and 28.8 % (17/59) of the ST group. CONCLUSIONS: Orbital radiotherapy in combination with steroid treatment significantly improved ocular motility by reducing EOM volume in patients with active GO. PMID- 26876242 TI - Introductory Note. PMID- 26876241 TI - Adverse effects of a 10-day course of ibuprofen in Holstein calves. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for various conditions in cattle. Ibuprofen is an inexpensive short-acting NSAID and is readily available in liquid formulation for administration to bottle-fed calves. We compared the adverse effects of a 10-day course of ibuprofen and placebo in 16 five- to six-week-old Holstein bull calves that were being treated for experimentally induced bovine respiratory syncytial virus infection. Ibuprofen was administered as a liquid in milk replacer at 30 mg/kg divided three times daily. We found an increased prevalence of abomasal ulceration 5 of 8 in the ibuprofen compared to placebo group 2 of 6 (P = NS). There was one (1 of 8) case of mild interstitial nephritis in the ibuprofen and none (0 of 8) in the placebo group (P = NS). Renal function as measured by serum BUN and creatinine levels was not different between groups; no animal demonstrated an increase in creatinine. PMID- 26876243 TI - Exploring the universal ecological responses to climate change in a univoltine butterfly. AB - Animals with distinct life stages are often exposed to different temperatures during each stage. Thus, how temperature affects these life stages should be considered for broadly understanding the ecological consequences of climate warming on such species. For example, temperature variation during particular life stages may affect respective change in body size, phenology and geographic range, which have been identified as the "universal" ecological responses to climate change. While each of these responses has been separately documented across a number of species, it is not known whether each response occurs together within a species. The influence of temperature during particular life stages may help explain each of these ecological responses to climate change. Our goal was to determine if monthly temperature variation during particular life stages of a butterfly species can predict respective changes in body size and phenology. We also refer to the literature to assess if temperature variability during the adult stage influences range change over time. Using historical museum collections paired with monthly temperature records, we show that changes in body size and phenology of the univoltine butterfly, Hesperia comma, are partly dependent upon temporal variation in summer temperatures during key stages of their life cycle. June temperatures, which are likely to affect growth rate of the final larval instar, are important for predicting adult body size (for males only; showing a positive relationship with temperature). July temperatures, which are likely to influence the pupal stage, are important for predicting the timing of adult emergence (showing a negative relationship with temperature). Previous studies show that August temperatures, which act on the adult stage, are linked to range change. Our study highlights the importance of considering temperature variation during each life stage over historic time-scales for understanding intraspecific response to climate change. Range edge studies of ectothermic species that have annual life cycles, long time-series occurrence data, and associated temperature records (ideally at monthly resolutions) could be useful model systems for intraspecific tests of the universal ecological responses to climate change and for exploring interactive effects. PMID- 26876244 TI - Brain fluorodeoxyglucose (FDG) PET in dementia. AB - The purpose of this article is to present a selective and concise summary of fluorodeoxyglucose (FDG) positron emission tomography (PET) in dementia imaging. FDG PET is used to visualize a downstream topographical marker that indicates the distribution of neural injury or synaptic dysfunction, and can identify distinct phenotypes of dementia due to Alzheimer's disease (AD), Lewy bodies, and frontotemporal lobar degeneration. AD dementia shows hypometabolism in the parietotemporal association area, posterior cingulate, and precuneus. Hypometabolism in the inferior parietal lobe and posterior cingulate/precuneus is a predictor of cognitive decline from mild cognitive impairment (MCI) to AD dementia. FDG PET may also predict conversion of cognitively normal individuals to those with MCI. Age-related hypometabolism is observed mainly in the anterior cingulate and anterior temporal lobe, along with regional atrophy. Voxel-based statistical analyses, such as statistical parametric mapping or three-dimensional stereotactic surface projection, improve the diagnostic performance of imaging of dementias. The potential of FDG PET in future clinical and methodological studies should be exploited further. PMID- 26876245 TI - [Efficacy and safety of deferasirox in aplastic anemia patients with iron overload: a single arm, multi-center,prospective study in China]. AB - OBJECTIVE: To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload. METHODS: A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg.kg(-1).d(-1), and the safety in 64 AA patients with iron overload. RESULTS: All patients started their deferasirox treatment with a daily dose of 20 mg . kg(-1) .d(-1). The mean actual dose was (18.6+/-3.60) mg . kg( 1).d(-1). The median SF decreased from 4 924 (2 718- 6 765)MUg/L at baseline (n=64) to 3 036 (1 474- 5 551)MUg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)MUg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)MUg/L [5 271(3 420-8 278)MUg/L at baseline; 3 036(1 474-5 551)MUg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 *ULN or >10 * ULN during the whole study. In AA patients with low baseline PLT count (less than 50 * 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period. CONCLUSIONS: AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events. PMID- 26876246 TI - [Dasatinib treatment based on BCR- ABL mutation detection in imatinib- resistant patients with chronic myeloid leukemia]. AB - OBJECTIVE: To evaluate the efficiency of dasatinib as the second- or third-line tyrosine kinase inhibitor (TKI)in imatinib-resistant patients with chronic myeloid leukemia (CML)based on BCR-ABL mutation detection. METHODS: 122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib- and nilotinib-resistance, 55 in the chronic-phase (CP), 21 in the accelerated- phase (AP)and 46 in the blast- phase (BP). Those harboring dasatinib highly- resistant mutations (T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival (PFS)and overall survival (OS)were analyzed. BCR- ABL mutation detection was performed once the patients failed on dasatinib. RESULTS: In the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR)and molecular response 4.5 (MR4.5)were 92.7%, 53.7%, 29.6% and 14.8%, respectively. 4-year PFS and OS rates were 84.4% and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0% and 35.0%; and 3 year PFS and OS rates were 56.1% and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0% and 21.4%; and 1-year PFS and OS rates were 43.6% and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second- line TKI or the third-line TKI. Of the 75 patients who were resistant to dasatinib, 37 (48.7%)developed new mutation(s), and T315I (59.5%)was the most common mutation type. The patients who already harbored mutation(s)before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib (65.7%vs 34.1%,P=0.006). CONCLUSIONS: Dasatinib was proved to be effective in the treatment of imatinib- or/and nilotinib-resistant CML patients, especially in both CP and AP cohorts. The significance of BCR-ABL mutation screening and monitoring should be highlighted before and during dasatinib therapy. PMID- 26876247 TI - [Efficacy and prognostic factors of induction therapy combined with autologous stem cell transplantation in 201 patients with multiple myeloma]. AB - OBJECTIVE: To explore the efficacy and prognostic factors of induction therapy combined with autogenetic peripheral blood stem cells transplantation (APBSCT)in patients with multiple myeloma (MM). METHODS: From January 1998 to May 2015, 201 patients with MM were enrolled. All patients received APBSCT after induction therapy. With the follow up to 20 June 2015, the overall survival (OS), progression free survival (PFS)and prognostic factor were analyzed. RESULTS: 1 With a media follow up of 36.67 months, the median PFS and OS were 22.87 (17.48- 28.26)and 69.63 (63.57- 75.69)months, 5-year PFS and OS were 17% and 49%, respectively. 2After APBSCT, when the subgroup (n= 112) achieved complete response (CR)compared with the subgroup (n=89) not achieved CR, the median PFS were 32.93 (21.03-44.83) and 18.13 (14.46-21.80) months (P<0.001), respectively; And the media OS were 96.77 (71.79- 121.75)and 54.70 (49.53- 59.87) months (P=0.004), respectively. The risks for disease progression and death declined in CR subgroup. 3 Two subgroups included or not included bortezomib/thalidomide at induction therapy (123 patientsvs 21 patients), the media PFS were 31.67 (24.36- 38.98)and 15.20 (10.11- 20.29) months (P=0.013), respectively; And the media OS were 76.30 (55.44- 97.15)and 52.03 (33.76- 70.30) months (P=0.014), respectively. 4According to the ISS stage, the media OS of stageI, II, III were 99.47 (59.58 139.36), 66.77 (52.17-81.37), 53.97 (28.71-79.23) (P< 0.001), respectively. The risk for death of stage II, III were 2.16 and 3.04 times higher than stage I, with no difference in terms of PFS. 5 The media PFS in IgD (n=22) and IgG (n=101) type MM were 11.17 (10.27- 13.13)and 35.43 (22.69- 48.17)months (P=0.007) , respectively; The media OS were 30.83 (0.24-61.42)and 70.70 (53.52-87.88) months (P=0.039), respectively. The risk for disease progression of IgD type was 2.47 times higher than IgG type. 6 Patients received 1 line induction therapy (n=132) compared with more than 1 line (n=69), the media PFS were 25.43 (16.09- 34.77)and 20.27 (15.04- 25.50) months (P=0.042). 7Cox analysis showed that CR after APBSCT and ISS stage were independent prognostic factors for OS. IgD type MM and CR after APBSCT were independent prognosis factor for PFS. CONCLUSION: CR after APBSCT and ISS stage were independent prognostic factors for OS in MM. CR after APBSCT was independent prognostic factor for PFS in MM. However, disease progression more likely occurred in IgD type MM, which was independent negative prognostic factor for PFS in MM. PMID- 26876248 TI - [The role of different KIR haplotypes in haplo-identical hematopoietic stem cell transplantation]. AB - OBJECTIVE: To investigate the role of different immunoglobulin- like receptor (KIR)haplotypes in haplo- identical hematopoietic stem cell transplantation (HSCT). METHOD: Killer cell KIR genotyping was performed on 468 individuals from 156 unrelated families by PCR-SSP. A total of 624 KIR haplotypes from the parents were used for haplotype analysis. Ninety-two patients received haplo-identical HSCT from one of the parents. RESULTS: The family study showed segregation of one A haplotype and at least 20 unique B haplotypes. The frequency of haplotype A was 72.92% (455/624). The most commonly observed haplotypes in group B were B1, B2, and B3, present at a frequency of 10.26%, 5.77%, and 4.48%, respectively. Compared to KIR gene matched donors (n=17), grafts from KIR gene mismatched donors (n= 14) had a positive effect on survival after haplo- identical HSCT for AML/MDS patients (OS: 88.2%vs 42.9%,P=0.015; RFS: 88.2%vs 35.7%,P=0.007). No effect was observed for ALL/NHL patients (OS: 76.0%vs 75.0%,P=0.727; RFS: 68.0%vs 65.0%,P=0.866). A significantly lower survival rate was observed for transplants from AA (n=52) and AB1/AB2 donors (n=15), compared to other group Bx donors (n=25) (OS: 53.3%vs 96.0%,P=0.017; RFS: 53.3%vs 92.0%,P=0.019). Meanwhile, the risk of relapse was much higher in AA group (n=52) compared to Bx group (n=40) (25.0%vs 5.0%,P=0.009). A higher risk of TRM was observed in AB1/AB2 group (P=0.012). In addition, transplant from donors carried Cen-B was associated with an increased survival compared with Cen-A homozygous donors (OS: 94.7%vs 68.5%,P=0.036; RFS: 89.5%vs 64.4%,P=0.045). CONCLUSION: Overall, KIR genotyping and haplotype analyses should be useful for selection of the most optimal donors with favorable KIR gene grafts. KIR gene mismatch donors should be preferred for AML/MDS patients. Selecting donors carried Cen- B and avoiding the selection of donors of KIR genotype AA/AB1/AB2 was strongly advisable for haplo-identical HSCT. PMID- 26876249 TI - [The assessment of symptomatic burden among Ph/BCR- ABL negative myeloproliferative neoplasm patients]. AB - OBJECTIVE: To investigate the value of myeloproliferative neoplasms Symptom Assessment Form total symptom score (MPN-SAF-TSS)in assessing constitutional symptoms among Ph/BCR- ABL negative myeloproliferative neoplasm (MPN)patients. METHODS: A cohort of 628 MPN patients were evaluated by MPN- SAF- TSS. RESULTS: Fatigue was the most common symptom (76.0%, 76.2%vs 89.9%)and the highest average severity of all the symptoms (3.46+/-2.97, 3.47+/-2.99vs 4.74+/-3.04 scores)among polycythemia vera (PV), essential thrombocythemia (ET)and primary myelofibrosis (PMF)patients. Using the MPN- SAF- TSS analysis, PMF patients showed highest burden of symptoms (28.9 +/- 19.1), followed by PV patients (19.2 +/- 16.8), and finally ET patients (17.1 +/- 15.3). Instinct differences were observed between PMF and PV patients (chi(2)=6.371,P=0.021), PMF and ET patients (chi(2)= 14.020,P<0.001). No significant difference was found between PV and ET patients (chi(2)=2.281,P=0.191). CONCLUSION: MPN- SAF- TSS was effective in evaluating the symptomatic burden among Ph/BCRABL negative MPN patients and could be used for serial assessment in this clinical setting. PMID- 26876250 TI - [Expression and prognostic value of CARD11 in diffuse large B cell lymphoma]. AB - OBJECTIVE: To determine the CARD11 expression and its prognostic value in diffuse large B cell lymphoma (DLBCL). METHODS: This retrospective study included previously untreated patients diagnosed with DLBCL from January 2007 to December 2012. Formalin-fixed, paraffin-embedded blocks of these patients were collected. Tissue microarray was built and expression of CARD11 was examined immunohistochemically. Subtype of DLBCL was determined by Hans algorithm (CD10, BCL6, MUM1). The pattern of CARD11 was further studied and their correlation with outcome was analyzed. RESULTS: 79 patients with DLBCL were enrolled and two reactive lymph nodes were used as control. The positive rate of high CARD11 expression in DLBCL was 65.33%, which showed no significant associations with patients' characteristics. Positive CARD11 expression was associated with an inferior event free survival (EFS)(2- year EFS: 52.03%vs 86.12%,P=0.036). Even in patients with a high international prognostic index (IPI, 3-5 points), this difference still remained significant (Median EFS not reached vs 557 days,P=0.033). CONCLUSION: DLBCL patients with high CARD11 expression had a shorter EFS compared with low level of CARD11. This difference remained significant when patients were in high IPI (3-5 points), which might indicate the value of CARD11 in stratification of high-risk DLBCL patients. PMID- 26876251 TI - [HLA- haploidentical donor hematopoietic transplantation for severe aplastic anemia achieved comparable outcomes with HLA- unrelated donor transplantation]. AB - OBJECTIVE: To evaluate the efficacy of HLA- haploidentical donor hematopoietic transplantation (Haplo- HSCT)for severe aplastic anemia (SAA)by compared with the same period of unrelated donor transplantation (UD- HSCT). METHODS: Of a cohort of 50 SAA patients between September 2012 and July 2014, 26 patients underwent UD HSCT and 24 patients Haplo- HSCT. RESULTS: OS rate was 91.3% with a median follow-up of 9 (2-26)months. According to transplant type, there was no significant difference between UD- and Haplo-HSCT (96.1%vs 86.0%,P=0.30). 3 of 50 (6%)patients had primary engraft failure. Haplo- HSCT developed higher significantly incidence of II- IV aGVHD (37.5%vs 3.83%,P=0.003)and cGVHD (37.5%vs 15.3%,P=0.030)than UD-HSCT. Haplo-HSCT also had significantly higher incidences of CMV viremia (78.2%vs 46.1%,P=0.005)and EBV viremia (43.1%vs 16.0%,P=0.040), respectively than UD-HSCT. But the incidences of hemorrhagic cystitis were similar between two transplant types (39.1%vs 23.0%,P=0.120). CONCLUSION: This study showed favorable outcome of Haplo-HSCT for SAA, which was comparable with UD-HSCT. PMID- 26876252 TI - [Marginal zone lymphoma with monoclonal immunoglobulin: three cases report and literatures review]. AB - OBJECTIVE: To investigate the clinical features and treatment in patients of marginal zone lymphoma (MZL)with monoclonal immunoglobulin (McIg). METHODS: The clinical data of MZL patients with McIg, including 3 cases diagnosed and treated in Beijing Anzhen Hospital from Jan 2007 to Dec 2014 were retrospectively studied, meanwhile 36 patients searched from literatures were reviewed. RESULTS: Of a total of 39 patients, the ratio of male and female was 1.05?1 with an average age of 65.1+/- 12.3 years old. 28 cases (71.8%)were with mucosa associated lymphoid tissue lymphomas (MALTL), 9 cases (23.1% )with nodal marginal zone lymphoma, and 2 cases (5.1%)with splenic marginal zone lymphoma. Nine cases (23.1% )were in the early stage, 30 cases (76.9%)in the advanced stage. The common initial symptom was non-mass lesions (65.5%), such as skin purpura, peripheral neuropathy; 13 patients (33.3% )were accompanied by autoimmune phenomenon, and most were with Sjogren's syndrome. Among MALTL patients, the common primary lesion was in non- gastrointestinal tract (17 cases, 60.7%). Most of patients with McIg were one with McIgM (82.0%); the others with McIgA, Mckappa light chain, McIgG and double McIg. The level of plasma McIgM was (25.55+/ 21.31)g/L, which was higher in advanced stage patients than in early stage ones [(29.85+/-20.60)g/Lvs (3.23+/-2.95)g/L,P= 0.008]. The complete remission (CR)rate was 56.0% and the overall response rate (ORR)92.0%, respectively in 30 patients treated by chemotherapy. At a median follow- up of 10 months, the 3- year progression free survival and the 3-year overall survival were 44.7% and 76.5%, respectively. The rates of ORR and CR in the patients received rituximab- included regimen were seemly better than those without rituximab one (100.0%vs 78.6%, 63.6%vs 50.0%;P>0.05), but no statistic differences were found. The CR rate in patients with McIgM was significantly higher than that with non- McIgM (P=0.026). The plasma McIgM level decreased after chemotherapy (P=0.002). CONCLUSION: The MZL with McIg, perhaps a kind of unique subtype, usually occurred in 60 years or older patients. It was often diagnosed in patients of advanced stage and susceptible to autoimmune phenomenon. MALTL in non- gastrointestinal tract was more prone to find McIg. In MZL patients with McIg, McIgM was more common and other McIg rare. Rituximab-included regimen produced a better therapeutic response. PMID- 26876253 TI - [The induction and cryopreservation of erythroid progenitor cells derived from umbilical cord blood mononuclear cells]. AB - OBJECTIVE: To discover the techniques for ex vivo generation and cryopreservation of erythroid progenitor cells (EPCs)derived from umbilical cord blood (UCB)mononuclear cells (MNCs). METHODS: UCB was chosen as the source of EPCs. Erythrocytes were precipitated by hydroxyethyl starch (HES). MNCs were separated by Ficoll density gradient centrifugation. Erythroid progenitor cell were generated from MNC ex vivo in suspension culture supplemented with stem cell growth factor, insulin growth factor, erythropoietin, Fms- liketyrosinekinase ligand, transferrin and dexamethasone. Cell maturation was evaluated by morphologic analysis and CD71/CD235a expression profiling. In vitro induced cells were cryopreserved using different cryopreservation media. The cell survival rate, phenotype and proliferation curves were detected after cell thawing. RESULTS: With the extension of culture time, the total number of cells increased significantly accompanied with the elevation of CD71 and CD235 positive populations. After 14- day inducing, the cells reached to approximately 110 times of the starting number with the cell viability as (88.92+/-0.95)%. The percentages of cell surface markers were (86.77+/-9.11)% for CD71 and (64.47+/ 16.67)% for CD71/CD235, respectively. With the extension of inducing time, wright Giemsa staining showed that the middle erythroblasts appeared mostly at day 10, and the late erythroblasts were seen at day 14. The red pellets were present at day 14, which indicated the more production of hemoglobin. Colony forming assay showed that erythroid colonies at induction day 7 were higher than that for non induced cells (326.00+/-97.96vs 61.60+/-20.03 per 2 000 cells). With the extension of culture time, the number of erythroid colonies decreased. Induced EPCs were preserved with different cryopreservation solutions, in which 10% DMSO were better than 5% DMSO. Additionally, 10% DMSO + 2% HSA showed no different with 10% DMSO + 5% HSA. Combined 50% plasma with 2% HSA was more effective. CONCLUSIONS: This non- serum culture media could effectively induced and expanded EPCs, and 10% DMSO + 2% HSA + 50% plasma appeared to be a desirable cryopreservation solution for EPCs from UCB. PMID- 26876254 TI - [Promoter methylation status of SFRP genes and induced apoptosis by demethylation in Jurkat cells]. AB - OBJECTIVE: To study the promoter methylation status of SFRP genes and the effect of 5- aza- 2'- deoxycytidine (5- Aza- CdR)induced apoptosis via Wnt/beta- catenin pathway by demethylation in Jurkat cells. METHODS: Jurkat cells were treated with different concentrations of 5- Aza- CdR. The cell proliferation level of Jurkat cells was detected by MTT assay. Apoptosis was evaluated by flow cytometry. Methylation- spcific PCR (MSP) was used to determine the methylation status of SFRP genes. The expressions of SFRP genes were detected by real time fluorescence quantitative PCR. The mRNA expression levels of survivin, c- myc and cyclin- D1 were analyzed by RT- PCR. Western blot was used to detect the levels of beta catenin protein. RESULTS: Compared with control group, the different concentrations of 5-Aza-CdR could significantly inhibit the proliferation of Jurkat cells in a time-dose dependent manner (P<0.05). After being treated by 5- Aza- CdR for 48 hours, the cell early apoptosis rate in experiment group was significantly higher than that in control group (P<0.05). The promoters of SFRP1, SFRP2, SFRP4, SFRP5 genes were hypermethylation state in the control group, after being treated by 5-Aza-CdR for 72 hours, the brightness of SFRP1, SFRP2, SFRP4, SFRP5 genes' methylation strips weakened in a dose- dependent manner. SFRP mRNA expression increased (P<0.05) when 5- Aza- CdR concentration increased, and the level of beta- catenin protein was dampened in a dose- dependent manner (P<0.05). As compared to the control group, the mRNA expressions of associated apoptosis genes survivin, c-myc and cyclin- D1, respectively were obviously down- regulated in a dose- dependent manner (P<0.05). CONCLUSION: The effect of demethylation could up- regulate SFRP genes expressions by reversing its hypermethylation and induced apoptosis by down-regulation of beta-catenin and associated apoptosis genes. PMID- 26876255 TI - [Antiproliferative effect of silencing LSD1 gene on Jurkat cell line and its mechanism]. AB - OBJECTIVE: To investigate the effect of silencing LSD1 gene by RNA interference on the proliferation, apoptosis on human lymphocytic leukemia Jurkat cell line and its mechanism. METHODS: The hairpin- like oligonucleotide sequences targeting LSD1 gene was transfected into Jurkat cells by lipofectamine(TM) 2000. The LSD1 mRNA and protein were detected by RQ- PCR and Western blot. Cell growth was determined by MTT. Cell apoptosis was analyzed by flow cytometry. The expression of Bcl-2, Bax, procaspase- 3, and histone H3K4me, H3K4me2, H3K4me3, Act- H3, H3K9me were detected by Western blot. RESULTS: LSD1 mRNA was markedly suppressed by the shRNA targeting LSD1. LSD1 shRNA suppressed the proliferation and induced cells apoptosis of Jurkat cells. The cell apoptotic rate was (41.34+/-3.58)%, (3.45+/-1.54)%, (1.76+/-0.52)% in LSD1 shRNA, Neg-shRNA and Blank respectively, the difference among them was statistically significant (P<0.05). LSD1 shRNA down regulated the expressions of Bcl- 2 and procaspase- 3, and up- regulated the expression of Bax. The methylation of H3K4me1, me2 and acetylation of Act- H3 improved without change of the methylation of H3K4me3. CONCLUSIONS: Deplete of LSD1 gene maybe through modifying the methylation of histone H3K4 to promote the cell apoptosis and inhibit cell growth in Jurkat cell line. PMID- 26876256 TI - [Clinical characteristics and outcome of 216 indolent B cell lymphomas]. PMID- 26876257 TI - [Clinical analysis of four multiple myeloma patients with - 13/13q- and 17p]. PMID- 26876258 TI - [Acute promyelocytic leukemia with stat5b- RARalpha fusiongene: a case report and literatures review]. PMID- 26876259 TI - [Non- Hodgkin's lymphoma initially manifested with pleuraleffusion: seven case reports and literatures review]. PMID- 26876260 TI - [Pregnancy-associated lymphoma: report of three cases]. PMID- 26876261 TI - [Diagnostic and therapeutic advances in blastic plasmacytoid dendritic cell neoplasm]. PMID- 26876262 TI - [Progress of chronic graft-versus-host disease]. PMID- 26876263 TI - [Comprehensive diagnosis of hematologic neoplasms]. PMID- 26876264 TI - [Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia]. AB - Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia. PMID- 26876265 TI - [Various pathways leading to the progression of chronic liver diseases]. AB - As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression. PMID- 26876266 TI - [Banff score changes in kidneys from marginal donors]. AB - INTRODUCTION: Despite an increase in the number of cadaver donors and the number of overall organ transplantations, the dramatic increase in the waiting list makes it necessary to reconsider donor criteria. AIM: The authors examined whether differences could exist in the function and/or morphology of transplanted kidneys originated from marginal and ideal donors one and five years after transplantation. METHOD: Kidney function and histopathologic findings were analysed and compared one and 5 years after transplantation in 97 patients having marginal donor kidneys and 178 patients who received ideal donor kidneys. RESULTS: Serum creatinine level was significantly higher (p = 0.0001) and estimated glomerular filtration rate was significantly lower (p = 0.003) in patients having marginal donor kidneys as compared to those with ideal donor kidneys 5 years after transplantation. Morphological changes in the transplanted kidneys such as tubulitis (p = 0.014) and interstitial inflammation (p = 0.025) were significantly more frequently present in patients with marginal donor kidneys than in those with ideal donor kidneys one year after transplantation. CONCLUSION: Despite an absence of differences in kidney function one year after kidney transplantation between patients having marginal and ideal donor kidneys, morphologic differences in the transplanted kidneys can be detected between the two groups of patients. PMID- 26876267 TI - [Consumer knowledge about dietary fibre -- Results of a national questionnaire survey]. AB - INTRODUCTION: Dietary fibres are key elements of healthy and balanced diet. AIM: The aim of the present study was to explore consumers' knowledge considering fibre, their role in the purchasing decisions, and the cognition of the currently used as well as the possible information sources to encourage the fibre consumption. METHOD: A questionnaire survey was conducted with 303 respondents. RESULTS: Knowledge about the fibre sources has showed a kind of uncertainty of the respondents, while knowledge about their possible health effects was relatively profound. Internet appeared as a remarkable information source in the topic; however, results pointed out the importance of education, too. Participants more often consuming foodstuffs rich in fibre, women and respondents over 45 years old showed conscious attitudes regarding fibres. CONCLUSIONS: Guidelines and education containing authentic information and practical elements are essential, and as a result, consumers' latent knowledge will appear in their conscious food choice decisions. PMID- 26876269 TI - [Cancelled quarter century jubilee of Faculty of Medicine at University of Debrecen in 1943-44]. PMID- 26876268 TI - [Differential diagnosis of Graves' orbitopathy. Case report]. AB - Graves' orbitopathy is the extrathyroidal manifestation of Graves' disease, which is the most common cause of exophthalmos. As eye symptoms usually coincide with the development of thyrotoxicosis, the diagnosis of the disease is rarely difficult. The aim of the authors was to summarize the differential diagnosis of Graves' orbitopathy based on literature review and presentation of their own four problematic cases on this topic. They conclude that symptoms similar to endocrine orbitopathy are present in other disorders. Endocrinologists need to be aware of these other conditions to avoid treatment failures. PMID- 26876272 TI - Preventing HIV infection among injecting drug users in high-risk countries: an assessment of the evidence. PMID- 26876273 TI - Seductive delusions: how everyday people catch STDs. PMID- 26876271 TI - Asymmetric Preorganization of Inverted Pair Residues in the Sodium-Calcium Exchanger. AB - In analogy with many other proteins, Na(+)/Ca(2+) exchangers (NCX) adapt an inverted twofold symmetry of repeated structural elements, while exhibiting a functional asymmetry by stabilizing an outward-facing conformation. Here, structure-based mutant analyses of the Methanococcus jannaschii Na(+)/Ca(2+) exchanger (NCX_Mj) were performed in conjunction with HDX-MS (hydrogen/deuterium exchange mass spectrometry) to identify the structure-dynamic determinants of functional asymmetry. HDX-MS identified hallmark differences in backbone dynamics at ion-coordinating residues of apo-NCX_Mj, whereas Na(+)or Ca(2+) binding to the respective sites induced relatively small, but specific, changes in backbone dynamics. Mutant analysis identified ion-coordinating residues affecting the catalytic capacity (kcat/Km), but not the stability of the outward-facing conformation. In contrast, distinct "noncatalytic" residues (adjacent to the ion coordinating residues) control the stability of the outward-facing conformation, but not the catalytic capacity. The helix-breaking signature sequences (GTSLPE) on the alpha1 and alpha2 repeats (at the ion-binding core) differ in their folding/unfolding dynamics, while providing asymmetric contributions to transport activities. The present data strongly support the idea that asymmetric preorganization of the ligand-free ion-pocket predefines catalytic reorganization of ion-bound residues, where secondary interactions with adjacent residues couple the alternating access. These findings provide a structure-dynamic basis for ion coupled alternating access in NCX and similar proteins. PMID- 26876274 TI - Neuropsychiatry of creativity. AB - In this paper, we review in brief the development of ideas that over time have tried to explain why some individuals are more creative than others and what may be the neurobiological links underlying artistic creativity. We note associations with another unique human idea, that of genius. In particular, we discuss frontotemporal dementia and bipolar, cyclothymic mood disorder as clinical conditions that are helping to unravel the underlying neuroanatomy and neurochemistry of human creativity. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26876275 TI - Pharmacological and neuroethological study of the acute and chronic effects of lamotrigine in the genetic audiogenic seizure hamster (GASH:Sal). AB - The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic audiogenic seizure hamster (GASH:Sal), an animal model of audiogenic seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5-20mg/kg) or chronically via oral administration (20-25mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20-25mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". PMID- 26876276 TI - Syllabic parsing in children: a developmental study using visual word-spotting in Spanish. AB - Some inconsistency is observed in the results from studies of reading development regarding the role of the syllable in visual word recognition, perhaps due to a disparity between the tasks used. We adopted a word-spotting paradigm, with Spanish children of second grade (mean age: 7 years) and sixth grade (mean age: 11 years). The children were asked to detect one-syllable words that could be found at the beginning of pseudo-words, with the boundary between the word and the remaining letters being manipulated. The end of the embedded word could either match the syllabic boundary (e.g. the word FIN in the pseudo-word FINLO, where the syllable boundary is between N and L) or not (e.g. FINUS, where the syllable boundary is located between I and N). The results showed that children of both grades were faster in the syllabic than the non-syllabic condition, and that the magnitude of this effect was the same regardless of reading ability. The results suggest an early universality in the use of syllables in Spanish, regardless of reading level. PMID- 26876277 TI - Effectiveness of Azadirachta indica (neem) mouthrinse in plaque and gingivitis control: a systematic review. AB - OBJECTIVES: The aim of this systematic review was to evaluate the effectiveness of Azadirachta indica (neem)-based herbal mouthrinse in improving plaque control and gingival health. METHODS: Literature search was accomplished using electronic databases (PubMed, Cochrane Central Register of Controlled Trials and EMBASE) and manual searching, up to February 2015, for randomized controlled trials (RCTs) presenting clinical data for efficacy of neem mouthrinses when used alone or as an adjunct to mechanical oral hygiene as compared to chlorhexidine mouthrinses for controlling plaque and gingival inflammation in patients with gingivitis. RESULTS: Of the total 206 articles searched, three randomized controlled trials evaluating neem-based herbal mouthrinses were included. Due to marked heterogeneity observed in study characteristics, meta-analysis was not performed. These studies reported that neem mouthrinse was as effective as chlorhexidine mouthrinse when used as an adjunct to toothbrushing in reducing plaque and gingival inflammation in gingivitis patients. However, the quality of reporting and evidence along with methods of studies was generally flawed with unclear risk of bias. CONCLUSION: Despite the promising results shown in existing randomized controlled trials, the evidence concerning the clinical use of neem mouthrinses is lacking and needs further reinforcement with high-quality randomized controlled trials based on the reporting guidelines of herbal CONSORT statement. PMID- 26876278 TI - Group II introns: versatile ribozymes and retroelements. AB - Group II introns are catalytic RNAs (ribozymes) and retroelements found in the genomes of bacteria, archaebacteria, and organelles of some eukaryotes. The prototypical retroelement form consists of a structurally conserved RNA and a multidomain reverse transcriptase protein, which interact with each other to mediate splicing and mobility reactions. A wealth of biochemical, cross-linking, and X-ray crystal structure studies have helped to reveal how the two components cooperate to carry out the splicing and mobility reactions. In addition to the standard retroelement form, group II introns have evolved into derivative forms by either losing specific splicing or mobility characteristics, or becoming functionally specialized. Of particular interest are the eukaryotic derivatives the spliceosome, spliceosomal introns, and non-LTR retroelements-which together make up approximately half of the human genome. On a practical level, the properties of group II introns have been exploited to develop group II intron based biotechnological tools. WIREs RNA 2016, 7:341-355. doi: 10.1002/wrna.1339 For further resources related to this article, please visit the WIREs website. PMID- 26876281 TI - Electrolyte and acid-base abnormalities associated with purging behaviors. AB - OBJECTIVE: Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major electrolyte and acid-base abnormalities and their treatment methods. The body of rigorous, eating disorder-specific literature on this topical area is not robust enough to perform a systematic review as defined by PRISMA guidelines. Therefore, a qualitative review of mostly medical literature was conducted. RESULTS: Hypokalemia, hyponatremia, and sodium chloride-responsive metabolic alkalosis are the most common serum changes that occur as a result of purging behaviors. They vary depending on the mode and frequency of purging behaviors. They can all potentially cause dangerous medical complications and are in need of definitive medical treatment. DISCUSSION: Eating disorders that are associated with purging behaviors are associated with a number of electrolyte and acid-base changes which are complex in their origin, documented to be medically dangerous and this definitive treatment is necessary to help achieve a successful treatment outcome, and in need of definitive treatment as described herein. PMID- 26876280 TI - Prophylactic and abundant intake of alpha-lipoic acid causes hepatic steatosis and should be reconsidered in usage as an anti-aging drug. AB - The majority of research has suggested that alpha-lipoic acid (ALA) is a potential therapeutic agent for chronic diseases associated with oxidative stress, including atherosclerosis, diabetes, and neurodegeneration. Therefore, a nutritional supplementation with ALA is recommended although the effects of a short- and long-term intake of ALA on central organs in healthy individuals are not studied in detail yet. Therefore, liver tissue of 4 and 74 weeks ALA-treated healthy C57BL6/J mice with respect to lipid metabolism was analyzed. In doing so, it was shown that short-term and long-term ALA treatment caused a marked increase of beta-oxidation, as indicated by a significant rise of mRNA expression of fgf21, pparalpha, and its target genes, for example, acox1, cpt1alpha, and cpt2, as well as of Fgf21 plasma concentration. Glycolytic activity, as assessed by pklr1 mRNA expression and pyruvate kinase activity, was also found increased. In addition, it was shown that both short- and long-term ALA treatment increased cholesterol content, induced systemic triglyceridemia, and enhanced rxralpha and lxralpha mRNA expression. Despite the fact that short-term ALA intake reduced lipogenesis, as given by significant declines of fas and srebp1c mRNA expression, and that a long-term ALA intake induced a significant rise of these lipogenic genes, both treatment regimen caused fat accumulation. This, however, was more pronounced upon long-term ALA intake, leading to hepatic steatosis and liver injury, as indicated by increased inflammation and disruption of the general hepatic architecture. In summary, the prophylactic and abundant use of ALA under healthy conditions should be considered with caution. PMID- 26876279 TI - Cost-Effectiveness/Cost-Benefit Analysis of Newborn Screening for Severe Combined Immune Deficiency in Washington State. AB - OBJECTIVE: To evaluate the expected cost-effectiveness and net benefit of the recent implementation of newborn screening (NBS) for severe combined immunodeficiency (SCID) in Washington State. STUDY DESIGN: We constructed a decision analysis model to estimate the costs and benefits of NBS in an annual birth cohort of 86 600 infants based on projections of avoided infant deaths. Point estimates and ranges for input variables, including the birth prevalence of SCID, proportion detected asymptomatically without screening through family history, screening test characteristics, survival rates, and costs of screening, diagnosis, and treatment were derived from published estimates, expert opinion, and the Washington NBS program. We estimated treatment costs stratified by age of identification and SCID type (with or without adenosine deaminase deficiency). Economic benefit was estimated using values of $4.2 and $9.0 million per death averted. We performed sensitivity analyses to evaluate the influence of key variables on the incremental cost-effectiveness ratio (ICER) of net direct cost per life-year saved. RESULTS: Our model predicts an additional 1.19 newborn infants with SCID detected preclinically through screening, in addition to those who would have been detected early through family history, and 0.40 deaths averted annually. Our base-case model suggests an ICER of $35 311 per life-year saved, and a benefit-cost ratio of either 5.31 or 2.71. Sensitivity analyses found ICER values <$100 000 and positive net benefit for plausible assumptions on all variables. CONCLUSIONS: Our model suggests that NBS for SCID in Washington is likely to be cost-effective and to show positive net economic benefit. PMID- 26876282 TI - Evaluation of antibacterial activity of Stenotrophomonas maltophilia against Ralstonia solanacearum under different application conditions. AB - AIM: The aim of this study was the monitoring of different mechanisms involved in the antibacterial activity of the biocontrol agent, Stenotrophomonas maltophilia (PD4560), against Ralstonia solanacearum in vitro and in vivo. Optimization of conditions that favour these mechanisms was the second target of this study. METHODS AND RESULTS: Proteolytic activity of Sten. maltophilia (PD 4560), was tested on skimmed milk medium. The biocontrol agent was able to produce an alkaline serine protease enzyme with a molecular weight of 40 KDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses. Spraying of salicylic acid (SA) led to an increase in the efficacy of Sten. maltophilia in controlling the Ralstonia potato wilt while spraying of ammonium sulphate (AmS) did not affect the biocontrol efficacy. The efficacy was correlated with the expression of protease enzyme genes; Prt genes (mainly PrtP and Prt4) and PR genes (mainly PR-1 and PRQ) as evaluated using real-time polymerase chain reaction analysis. CONCLUSIONS: The biocontrol activity of Sten. maltophilia can be attributed to the direct mechanism alkaline serine proteolytic enzyme production and through induction of host systemic acquired resistance as indirect mechanism. Tuber bulking was the most suitable physiological growth stage to apply either SA or the biocontrol agent. SIGNIFICANCE AND IMPACT OF THE STUDY: Both SA and peat-moss as an organic carrier enhanced the antibacterial efficiency of the biocontrol agent. Application of Sten. maltophilia is more suitable under alkaline soil conditions. PMID- 26876283 TI - TopoisomeraseIIbeta in HIV-1 transactivation. AB - TopoisomeraseIIbeta, an isoform of type II topoisomerase, was found to be functional in various viral infections. Its plausible role in HIV life cycle was also suggested earlier, but not clearly established. In the present study, we have investigated the role of TopoIIbeta in HIV-1 infection by its gain and loss of function. Overexpression of TopoIIbeta lead to an increase in viral replication, resulting in enhanced virion production. HIV-1 replication was impaired when TopoIIbeta was down regulated by siRNA and inhibited by ICRF-193 and merbarone. The role of TopoIIbeta in HIV-1 transcription was shown through its interaction with Tat and recruitement to long terminal repeat (LTR) region by co-immunoprecipitation and ChIP assays. Involvement of TopoIIbeta in transactivation of HIV-1 LTR was confirmed by luciferase assay in reporter cell line, TZM bl and also by transfection of reporter exogenously. It was also observed that LTR transactivation commensurated with the expression of TopoIIbeta in the presence of Tat. In addition, a decreased viral gene expression on treatment with merbarone exemplifies the importance of catalytic activity of TopoIIbeta in viral replication. These observations indicate that TopoIIbeta is involved in the cascade of coactivator complexes that are recruited to LTR for regulation of HIV-1 transcription. PMID- 26876285 TI - Editorial: PPI-responsive oesophageal eosinophilia and long-term PPI treatment. PMID- 26876284 TI - Evaluation of a novel echocardiographic view for the assessment of the pulmonary artery in dogs. AB - OBJECTIVES: 1) To describe a novel echocardiographic view (left cranial oblique) for the assessment of the pulmonary artery in dogs 2) To compare this novel view with other standard views. ANIMALS: Prospective inclusion of 48 echocardiograms performed on client-owned dogs. METHODS: Two standard views and the novel view were compared for quality of 2D images and spectral Doppler traces and also for pulmonary annulus diameter and spectral Doppler velocities. Association between view, heart rate and body weight and quality, annulus diameter, pulsed-wave and continuous-wave velocities were analyzed using regression analysis. Agreement between views was assessed by Bland-Altman analysis. Pulsed-wave and continuous wave velocities were compared using the sign test for medians. RESULTS: Forty eight studies were undertaken of which thirty-nine were analyzed. The quality of 2D images was associated with view and heart rate. No significant difference was found in quality of spectral Doppler traces between views. Annulus diameter showed significant association with view, heart rate and weight. This measured about 0.26 cm less on one particular view. Spectral Doppler velocities showed no association with view, heart rate or weight. Continuous-wave velocities were significantly higher than pulsed-wave velocities in every view. CONCLUSIONS: The novel left cranial oblique view can be used as an additional tool for the echocardiographic evaluation of the pulmonary artery. The pulmonary annulus diameter was consistently smaller measured from the one standard view compared to both the novel and other standard views. Comparable quality and velocities were obtained for spectral Doppler. Continuous-wave and pulsed-wave modes were not interchangeable. PMID- 26876286 TI - Editorial: PPI-responsive oesophageal eosinophilia and long-term PPI treatment- authors' reply. PMID- 26876287 TI - Letter: aberrant GSTP1 promoter methylation in acute-on-chronic hepatitis B liver failure. PMID- 26876288 TI - Letter: aberrant GSTP1 promoter methylation in acute-on-chronic hepatitis B liver failure--authors' reply. PMID- 26876289 TI - Letter: long-term use of proton pump inhibitors and risk of neuroendocrine tumours. PMID- 26876290 TI - Letter: ileal bile acid transporter inhibition--is there a potential for drug drug interaction? PMID- 26876291 TI - Letter: ileal bile acid transporter inhibition- is there a potential for drug drug interaction? Authors' reply. PMID- 26876292 TI - Letter: self-pay behaviour patients with chronic hepatitis C who required direct acting anti-viral urgently in a real-world setting. PMID- 26876294 TI - Corrigendum. PMID- 26876293 TI - Erratum. PMID- 26876295 TI - Decreased Vertebral Artery Hemodynamics in Patients with Loss of Cervical Lordosis. AB - BACKGROUND Because loss of cervical lordosis leads to disrupted biomechanics, the natural lordotic curvature is considered to be an ideal posture for the cervical spine. The vertebral arteries proceed in the transverse foramen of each cervical vertebra. Considering that the vertebral arteries travel in close anatomical relationship to the cervical spine, we speculated that the loss of cervical lordosis may affect vertebral artery hemodynamics. The aim of this study was to compare the vertebral artery values between subjects with and without loss of cervical lordosis. MATERIAL AND METHODS Thirty patients with loss of cervical lordosis and 30 controls matched for age, sex, and body mass index were included in the study. Sixty vertebral arteries in patients with loss of cervical lordosis and 60 in controls without loss of cervical lordosis were evaluated by Doppler ultrasonography. Vertebral artery hemodynamics, including lumen diameter, flow volume, peak systolic velocity, end-diastolic velocity, and resistive index, were measured, and determined values were statistically compared between the patient and the control groups. RESULTS The means of diameter (p=0.003), flow volume (p=0.002), and peak systolic velocity (p=0.014) in patients were significantly lower as compared to controls. However, there was no significant difference between the 2 groups in terms of the end-diastolic velocity (p=0.276) and resistive index (p=0.536) parameters. CONCLUSIONS The present study revealed a significant association between loss of cervical lordosis and decreased vertebral artery hemodynamics, including diameter, flow volume, and peak systolic velocity. Further studies are required to confirm these findings and to investigate their possible clinical implications. PMID- 26876296 TI - Explaining differences in stakeholder take up of disease management programmes: A comparative analysis of policy implementation in Austria and Germany. AB - PURPOSE: Understanding why policies to improve care for people with chronic conditions fail to be implemented is a pressing issue in health system reform. We explore reasons for the relatively high uptake of disease management programmes (DMPs) in Germany, in contrast to low uptake in Austria. We focus on the motivation, information and power of key stakeholder groups (payers, physician associations, individual physicians and patients). METHODS: We conducted a comparative stakeholder analysis using qualitative data from interviews (n=15 in Austria and n=26 in Germany), legal documents and media reports. RESULTS: Stakeholders in Germany appeared to have systematically stronger motivation, exposure to more positive information about DMPs and better ability to implement DMPs than their counterparts in Austria. Policy in Austria focused on financial incentives to physicians only. In Germany, limited evidence about the quality improvement and cost savings potential of DMPs was mitigated by strong financial incentives to sickness funds but proved a fundamental obstacle in Austria. CONCLUSIONS: Efforts to promote DMPs should seek to ensure the cooperation of payers and patients, not just physicians, using a mix of financial and non financial instruments suited to the context. A singular focus on financially incentivising providers is unlikely to stimulate uptake of DMPs. PMID- 26876297 TI - Social network analysis of duplicative prescriptions: One-month analysis of medical facilities in Japan. AB - OBJECTIVES: Duplicative prescriptions refer to situations in which patients receive medications for the same condition from two or more sources. Health officials in Japan have expressed concern about medical "waste" resulting from this practices. We sought to conduct descriptive analysis of duplicative prescriptions using social network analysis and to report their prevalence across ages. METHODS: We analyzed a health insurance claims database including 1.24 million people from December 2012. Through social network analysis, we examined the duplicative prescription networks, representing each medical facility as nodes, and individual prescriptions for patients as edges. RESULTS: The prevalence of duplicative prescription for any drug class was strongly correlated with its frequency of prescription (r=0.90). Among patients aged 0-19, cough and colds drugs showed the highest prevalence of duplicative prescriptions (10.8%). Among people aged 65 and over, antihypertensive drugs had the highest frequency of prescriptions, but the prevalence of duplicative prescriptions was low (0.2 0.3%). Social network analysis revealed clusters of facilities connected via duplicative prescriptions, e.g., psychotropic drugs showed clustering due to a few patients receiving drugs from 10 or more facilities. CONCLUSION: Overall, the prevalence of duplicative prescriptions was quite low - less than 10% - although the extent of the problem varied by drug class and age group. Our approach illustrates the potential utility of using a social network approach to understand these practices. PMID- 26876298 TI - Overexpression of CD158 and NKG2A Inhibitory Receptors and Underexpression of NKG2D and NKp46 Activating Receptors on NK Cells in Acute Myeloid Leukemia. AB - BACKGROUND AND AIMS: Natural killer (NK) cells are innate immune system cells that are actively involved in immune-surveillance of tumor cells. Recognition of tumors by NK cells occurred via natural cytotoxicity receptors and killer cell immunoglobulin-like receptors. Some ligands of the activating receptors seem to be present on malignant cells from patients with acute myeloid leukemia. The aim of the study was to evaluate the expression of activating receptors such as NKG2D, DNAM-1, NKp30, and NKp46, and inhibitory receptors such as NKG2A, CD158b, CD158a, and CD158e1 on NK cells from patients with newly diagnosed acute myeloid leukemia before and after stimulation with IL-2 and IL-12. METHODS: Patients were divided into two groups: group 1 AML M3, and group 2 non-M3 AML. Flow cytometry was performed on whole PBMC to evaluate NK cell receptors. RESULTS: Twenty one AML patients, aged 26-78 years, and 11 matched healthy individuals were studied. NKG2D, and NKp46 expression was decreased in group 1 (p <0.019). Patients in Group 2 showed underexpression of the activating receptors NKp46. Differences after stimulation of NK cells with IL-2 and IL-12 were observed only in Group 2, in which a significant decrease in the expression of NKp46 receptor was found (p <0.0016). Patients in groups 1 and 2 showed overexpression of the inhibitory receptors CD158b (p <0.007) and NKG2A (p <0.01). CONCLUSIONS: NKG2D receptor expression is decreased in patients with AML M3. In addition, patients with all FAB types of AML have overexpression of inhibitory receptors such as CD158b and NKG2A and decreased expression of the activating receptor NKp46. PMID- 26876300 TI - Cytokine production and mRNA expression in pulmonary tuberculosis patients and their household contacts of younger age group (15-25years). AB - Household contacts of tuberculosis patients are at high risk of infection and development of active disease. In this study we evaluated the cytokine production and mRNA expression of IFN-gamma, TNF-alpha, IL-10&IL-6 stimulated with r32kDa M. bovis BCGAg in active pulmonary tuberculosis patients (APTB), household contacts (HHC) and healthy controls (HC). The results showed the stimulated levels of IFN gamma and TNF-alpha were low while IL-10 levels were high in APTB and HHC compared to HC. IL-6 has not shown any significant difference. The mRNA expression of TNF- alpha was 8 fold high in HCs compared to APTB and HHC. The IL 6 expression was 2.2 fold &1 fold less in APTB and HHC compared to HCs. Multinomial logistic regression analysis indicated that the stimulated levels of IFN-gamma & IL-6 and sex significantly predicted the HHC group from HCs at p<0.05.In conclusion further follow up studies with r32kd antigen might help to identify the high risk individuals. PMID- 26876299 TI - The beta isoform of GSK3 mediates podocyte autonomous injury in proteinuric glomerulopathy. AB - Converging evidence points to glycogen synthase kinase (GSK) 3 as a key player in the pathogenesis of podocytopathy and proteinuria. However, it remains unclear if GSK3 is involved in podocyte autonomous injury in glomerular disease. In normal kidneys, the beta isoform of GSK3 was found to be the major GSK3 expressed in glomeruli and intensely stained in podocytes. GSK3beta expression in podocytes was markedly elevated in experimental or human proteinuric glomerulopathy. Podocyte-specific somatic ablation of GSK3beta in adult mice attenuated proteinuria and ameliorated podocyte injury and glomerular damage in experimental adriamycin (ADR) nephropathy. Mechanistically, actin cytoskeleton integrity in podocytes was largely preserved in GSK3beta knockout mice following ADR insult, concomitant with a correction of podocyte hypermotility and lessened phosphorylation and activation of paxillin, a focal adhesion-associated adaptor protein. In addition, GSK3beta knockout diminished ADR-induced NFkappaB RelA/p65 phosphorylation selectively at serine 467; suppressed de novo expression by podocytes of NFkappaB-dependent podocytopathic mediators, including B7-1, cathepsin L, and MCP-1; but barely affected the induction of NFkappaB target pro survival factors, such as Bcl-xL. Moreover, the ADR-elicited podocytopenia and podocyte death were significantly attenuated in GSK3beta knockout mice, associated with protection against podocyte mitochondrial damage and reduced phosphorylation and activation of cyclophilin F, a structural component of mitochondria permeability transition pores. Overall, our findings suggest that the beta isoform of GSK3 mediates autonomous podocyte injury in glomerulopathy by integrating multiple podocytopathic signalling pathways. PMID- 26876301 TI - Generation of mouse and human dendritic cells in vitro. AB - Dendritic cells (DC) that can orchestrate immune responses and maintain host homeostasis, are indispensable components of the immune system. Although distributed widely in many lymphoid and non-lymphoid tissues, their rarity in number has become a limiting factor for DC related research and therapies. Therefore, methods for efficiently generating large numbers of DC resembling their in vivo counterparts are urgently needed for DC related research and therapies. Herein we summarize the current methods for generating mouse and human DC in vitro and hope that these will facilitate both studies of DC biology and their clinical applications. PMID- 26876302 TI - Mesenchymal stem cells exhibit resistance to topoisomerase inhibition. AB - BACKGROUND: Inhibition of cellular topoisomerases has been established as an effective way of treating certain cancers, albeit with often high levels of toxicity to the bone marrow. While the involvement of mesenchymal stem cells (MSCs) in bone marrow homeostasis and regeneration has been well established, the effects of topoisomerase-inhibiting anticancer agents remain largely unknown. MATERIALS AND METHODS: Human bone marrow MSCs were treated with topoisomerase I inhibitor irinotecan or topoisomerase II inhibitor etoposide, and survival and apoptosis levels were measured. The influence of topoisomerase inhibition on cellular morphology, adhesion and migration potential and the ability to differentiate was assessed. Additionally, the role of individual DNA double strand break repair pathways in MSCs was investigated as a potential cellular mechanism of resistance to topoisomerase inhibitors. RESULTS: Human bone marrow MSCs were found relatively resistant to topoisomerase I and II inhibitors and show survival levels comparable to these of differentiated fibroblasts. Treatment with irinotecan or etoposide did not significantly influence cellular adhesion, migratory ability, surface marker expression or induction of apoptosis in human MSCs. The ability to differentiate was found preserved in MSCs after exposure to high doses of irinotecan or etoposide. MSCs were able to efficiently repair DNA double-strand breaks induced by topoisomerase inhibitors both by non-homologous end joining and homologous recombination pathways. CONCLUSION: Our data demonstrate a topoisomerase-resistant phenotype of human MSCs that may at least in part be due to the stem cells' ability to efficiently remove DNA damage caused by these anticancer agents. The observed resistance of MSCs warrants further investigation of these cells as a potential therapeutic option for treating topoisomerase inhibitor-induced bone marrow damage. PMID- 26876304 TI - A new case of the enigmatic Candidatus Neoehrlichia sp. (FU98) in a fox from the Czech Republic. AB - This study reports a new case of Candidatus Neoehrlichia sp. (FU98) infection in a fox from the Czech Republic, and provides confirmatory evidence on the occurrence of this newly identified sequence type. However, further studies are needed to investigate the distribution, host range and possible vector(s) for this bacterium, as well as its impact on animals and humans. PMID- 26876303 TI - Testosterone affects language areas of the adult human brain. AB - Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26876305 TI - The unaccountable risks of LIBOR. AB - One of the on-going consequences of recent financial crises seems to be that the conventional 'anchor' measures of global finance (such as the US dollar, treasury bonds and AAA rated securities) are no longer playing the anchoring role once believed of them. LIBOR now needs to be added to this list and not just because it has been tarnished by illegal practices, but because it is looking increasingly surpassed by financial market practices. LIBOR was believed to provide a risk-free rate of interest, but has been revealed to be risk-laden. Moreover, LIBOR is a measure of the costs of borrowing, whilst market concern is increasingly with measures of interest rate volatility. This paper looks at why, in the context of crisis, financial market focus on interest rates is turning towards other benchmarks, notably the overnight indexed swap (OIS) market, and what this shift might be telling us about the anchoring requirements of global financial markets. PMID- 26876306 TI - RNA helicase Belle (DDX3) is essential for male germline stem cell maintenance and division in Drosophila. AB - The present study showed that RNA helicase Belle (DDX3) was required intrinsically for mitotic progression and survival of germline stem cells (GSCs) and spermatogonial cells in the Drosophila melanogaster testes. We found that deficiency of Belle in the male germline resulted in a strong germ cell loss phenotype. Early germ cells are lost through cell death, whereas somatic hub and cyst cell populations are maintained. The observed phenotype is related to that of the human Sertoli Cell-Only Syndrome caused by the loss of DBY (DDX3) expression in the human testes and results in a complete lack of germ cells with preservation of somatic Sertoli cells. We found the hallmarks of mitotic G2 delay in early germ cells of the larval testes of bel mutants. Both mitotic cyclins, A and B, are markedly reduced in the gonads of bel mutants. Transcription levels of cycB and cycA decrease significantly in the testes of hypomorph bel mutants. Overexpression of Cyclin B in the germline partially rescues germ cell survival, mitotic progression and fertility in the bel-RNAi knockdown testes. Taken together, these results suggest that a role of Belle in GSC maintenance and regulation of early germ cell divisions is associated with the expression control of mitotic cyclins. PMID- 26876307 TI - Epithelial membrane protein 2 regulates sphingosylphosphorylcholine-induced keratin 8 phosphorylation and reorganization: Changes of PP2A expression by interaction with alpha4 and caveolin-1 in lung cancer cells. AB - Sphingosylphosphorylcholine (SPC) is found at increased in the malignant ascites of tumor patients and induces perinuclear reorganization of keratin 8 (K8) filaments that contribute to the viscoelasticity of metastatic cancer cells. However, the detailed mechanism of SPC-induced K8 phosphorylation and reorganization is not clear. We observed that SPC dose-dependently reduced the expression of epithelial membrane protein 2 (EMP2) in lung cancer cells. Then, we examined the role of EMP2 in SPC-induced phosphorylation and reorganization of K8 in lung cancer cells. We found that SPC concentration-dependently reduced EMP2 in A549, H1299, and other lung cancer cells. This was verified at the mRNA level by RT-PCR and real-time PCR (qPCR), and intracellular variation through confocal microscopy. EMP2 gene silencing and stable lung cancer cell lines established using EMP2 lentiviral shRNA induced K8 phosphorylation and reorganization. EMP2 overexpression reduced K8 phosphorylation and reorganization. We also observed that SPC-induced loss of EMP2 induces phosphorylation of JNK and ERK via reduced expression of protein phosphatase 2A (PP2A). Loss of EMP2 induces ubiquitination of protein phosphatase 2A (PP2A). SPC induced caveolin-1 (cav-1) expression and EEA1 endosome marker protein but not cav-2. SPC treatment enhanced the binding of cav-1 and PP2A and lowered binding of PP2A and alpha4. Gene silencing of EMP2 increased and gene silencing of cav-1 reduced migration of A549 lung cancer cells. Overall, these results suggest that SPC induces EMP2 down-regulation which reduces the PP2A via ubiquitination induced by cav-1, which sequestered alpha4, leading to the activation of ERK and JNK. PMID- 26876308 TI - beta-Amyloid induces nuclear protease-mediated lamin fragmentation independent of caspase activation. AB - beta-Amyloid (Abeta), a hallmark peptide of Alzheimer's disease, induces both caspase-dependent apoptosis and non-apoptotic cell death. In this study, we examined caspase-independent non-apoptotic cell death preceding caspase activation in Abeta42-treated cells. We first determined the optimal treatment conditions for inducing cell death without caspase activation and selected a double-treatment method involving the incubation of cells with Abeta42 for 4 and 6 h (4+6 h sample). We observed that levels of lamin A (LA) and lamin B (LB) were reduced in the 4+6 h samples. This reduction was decreased by treatment with suc AAPF-CMK, an inhibitor of nuclear scaffold (NS) protease, but not by treatment with z-VAD-FMK, a pan-caspase inhibitor. In addition, suc-AAPF-CMK decreased the changes in nuclear morphology observed in cells in the 4+6 h samples, which were different from nuclear fragmentation observed in STS-treated cells. Furthermore, suc-AAPF-CMK inhibited cell death in the 4+6 h samples. LA and LB fragmentation occurred in the isolated nuclei and was also inhibited by suc-AAPF-CMK. Together, these data indicated that the fragmentation of LA and LB in the Abeta42-treated cells was induced by an NS protease, whose identity is not clearly determined yet. A correlation between Abeta42 toxicity and the lamin fragmentation by NS protease suggests that inhibition of the protease could be an effective method for controlling the pathological process of AD. PMID- 26876310 TI - h-indices: an update on the performance of professors in nursing in the UK. PMID- 26876309 TI - Predictors of cognitive decline and treatment response in a clinical trial on suspected prodromal Alzheimer's disease. AB - We determined the value of hippocampus (Hp) and basal forebrain (BF) volumes for predicting cognitive decline and treatment response in a double-blind, randomized, placebo-controlled phase 4 trial at 28 academic centers (France) in patients with amnestic mild cognitive impairment (MCI) receiving Donepezil 10 mg daily or placebo over 12 months, and 6 months open label follow-up. Outcome measures were the rates of global and domain specific cognitive decline as non primary efficacy endpoint. The intention-to-treat (ITT) sample analyzed comprised 215 cases. Baseline Hp volume was a significant predictor of rates of change in global cognitive function in linear mixed effects models. This effect was independent of treatment. BF volume was not associated with rates of global or domain specific cognitive decline. Rates of delayed free recall decline were higher in MCI cases treated with donepezil compared to placebo. Only Hp, but not BF volume was a useful predictor of cognitive decline in suspected prodromal AD patients. Both Hp and BF volumes were poor predictors of treatment response, questioning previous approaches on predicting treatment response without placebo control. TRIAL REGISTRATION: clinicalTrials.gov Identifier NCT00403520. PMID- 26876311 TI - Decreased protein S-palmitoylation in dorsolateral prefrontal cortex in schizophrenia. AB - Recent reports suggest abnormalities of neurotransmitter receptor trafficking, targeting, dendritic localization, recycling, and degradation in the brain in schizophrenia. We hypothesized that a potential explanation for these findings may be abnormal posttranslational modifications that influence intracellular targeting and trafficking of proteins between subcellular compartments. Dysregulation of protein palmitoylation is a strong candidate for such a process. S-palmitoylation is a reversible thioesterification of palmitoyl-groups to cysteine residues that can regulate trafficking and targeting of intracellular proteins. Using a biotin switch assay to study S-palmitoylation of proteins in human postmortem brain, we identified a pattern of palmitoylated proteins that cluster into 17 bands of discrete molecular masses, including numerous proteins associated with receptor signal transduction. Using mass spectrometry, we identified 219 palmitoylated proteins in human frontal cortex, and individually validated palmitoylation status of a subset of these proteins. Next, we assayed protein palmitoylation in dorsolateral prefrontal cortex from 16 schizophrenia patients and paired comparison subjects. S-palmitoylation was significantly reduced for proteins in most of the 17 schizophrenia bands. In rats chronically treated with haloperidol, the same pattern of palmitoylation was observed but the extent of palmitoylation was unchanged, suggesting that the diminution in protein palmitoylation in schizophrenia is not due to chronic antipsychotic treatment. These results indicate there are changes in the extent of S-palmitoylation of many proteins in the frontal cortex in schizophrenia. Given the roles of this posttranslational modification, these data suggest a potential mechanism reconciling previous observations of abnormal intracellular targeting and trafficking of neurotransmitter receptors in this illness. PMID- 26876312 TI - Cortical thinning in bipolar disorder and schizophrenia. AB - Although schizophrenia (SZ) and bipolar disorder (BD) share some clinical features such as psychotic symptoms and cognitive dysfunctions, little is known about possible pathophysiological similarities between both diseases. Therefore, we investigated the potential topographical overlap and segregation of cortical thickness abnormalities in SZ and BD patients. We analyzed 3D-anatomical magnetic resonance imaging datasets with the FreeSurfer 5.1.0 software to examine cortical thickness and volumes in three groups of participants: n=34 BD patients, n=32 SZ patients and n=38 healthy controls. We observed similar bilateral cortical thickness reductions in BD and SZ patients predominantly in the pars opercularis of the inferior frontal gyrus and in the anterior and posterior cingulate. We also found disease-specific cortical reductions in the orbitofrontal cortex for BD patients and in dorsal frontal and temporal areas for SZ. Furthermore, inferior frontal gyrus cortical thinning was associated with deficits in psychomotor speed and executive functioning in SZ patients and with age at onset in both groups. Our findings support the hypothesis that thinning of the frontal cortex may represent a biological feature shared by both disease groups. The associations between cognitive deficits and the reported findings in SZ and to a lesser degree in BD patients add to the functional relevance of our results. However, further studies are needed to corroborate a model of shared pathophysiological disease features across BD and SZ. PMID- 26876313 TI - Cannabis-induced psychosis associated with high potency "wax dabs". AB - With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. PMID- 26876314 TI - Effect of hyperglycemia on the number of CD117+ progenitor cells and their differentiation toward endothelial progenitor cells in young and old ages. AB - Dysfunction of endothelial progenitor cells (EPCs) has been reported either in aging or diabetes, though the influence of an "old" environment on numerical and functional changes of diabetes associated EPCs is not known. We evaluated the effect of both aging and early stage of streptozotocin-induced diabetes on the number of bone marrow-derived CD117+ progenitor cells, and on their differentiation in vitro toward EPCs. The phenotype of progenitor cells and the uptake of acetylated-low density lipoprotein (Ac-LDL) were evaluated after cell culture in VEGF, FGF-1, and IGF-1 supplemented medium. Hyperglycemia similarly reduced the number of CD117+ cells both in young and old mice. CD117+ cells from young mice differentiated better than those from old animals "in vitro", with a greater reduction of CD117+ cells and an higher increase of CD184+VEGFR-2+ cells. In diabetic mice, in vitro CD117+ cells differentiation was significantly reduced in young animals. Diabetes did not impact on the scarce differentiation of CD117+ cells from old mice. Hyperglycemia reduced the uptake of acLDL by EPCs greatly in young than in old mice. These findings indicate that part of the EPCs functional alterations induced by hyperglicemia in young mice are observed in normal aged mice. PMID- 26876315 TI - Discriminating Between Bipolar Disorder and Major Depressive Disorder. AB - Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder. PMID- 26876316 TI - Treatment of Bipolar Depression: Evolving Recommendations. AB - Bipolar depression is the most common and difficult-to-treat phase of bipolar disorder. Antidepressants for unipolar depression are among the most widely used drugs, but recent data and meta-analyses indicate a lack of efficacy. Many of the drugs discussed here are graded provisionally for the strength of the findings in the literature, safety and tolerability, and likely utility of use in patients with bipolar disorder. Successful long-term treatment of bipolar depression is critical to preventing illness-related morbidity, disability, cognitive decline, suicide, and premature loss of years of life expectancy largely from the excess medical mortality associated with cardiovascular disorders. PMID- 26876317 TI - Psychotherapeutic Treatment of Bipolar Depression. AB - The gold standard for treating bipolar depression is based on the combination of mood stabilizers and psychotherapy. Therefore, the authors present evidence-based models and promising approaches for psychotherapy for bipolar depression. Cognitive-behavioral therapy, family focused therapy, interpersonal and social rhythm therapy, mindfulness-based cognitive therapy, and dialectical behavior therapy are discussed. Behavioral activation, the cognitive behavioral analysis system of psychotherapy, and the unified protocol as promising future directions are presented. This review informs medical providers of the most appropriate referral guidelines for psychotherapy for bipolar depression. The authors conclude with a decision tree delineating optimal referrals to each psychotherapy approach. PMID- 26876318 TI - Bipolar Depression: Pregnancy, Postpartum, and Lactation. AB - Medication management of bipolar depression in pregnancy and lactation is best done by assessing each patient's and family's needs in detail. Keeping pregnant patients as psychiatrically stable as possible is the most important principle for clinicians. Unfortunately, there is no risk-free situation for patients with psychiatric illness. This is often the most difficult and hard to accept reality for these patients, families, and clinicians. Clinicians serve these patients best by being as transparent as possible about the risk/benefit analysis of each patient's situation with the realization that ultimately the decisions are made by the patient and family. PMID- 26876319 TI - Nutrition and Bipolar Depression. AB - As with physical conditions, bipolar disorder is likely to be impacted by diet and nutrition. Patients with bipolar disorder have been noted to have relatively unhealthy diets, which may in part be the reason they also have an elevated risk of metabolic syndrome and obesity. An improvement in the quality of the diet should improve a bipolar patient's overall health risk profile, but it may also improve their psychiatric outcomes. New insights into biological dysfunctions that may be present in bipolar disorder have presented new theoretic frameworks for understanding the relationship between diet and bipolar disorder. PMID- 26876320 TI - The Influence of Trauma, Life Events, and Social Relationships on Bipolar Depression. AB - A growing body of research suggests that the social environment exerts a powerful influence on the course of bipolar depression. This article reviews longitudinal research to suggest that trauma, negative life events, social support deficits, and family difficulties are common and predict a more severe course of depression when present among those diagnosed with bipolar disorder. The triggers of bipolar depression overlap with those documented for unipolar depression, suggesting that many of the treatment targets for unipolar depression may be applicable for bipolar depression. PMID- 26876322 TI - Suicide Behaviors in Bipolar Disorder: A Review and Update for the Clinician. AB - Suicide behaviors (ideation, attempts, and completions) are unfortunately common in patients with bipolar disorder. It is estimated that 25 to 50% attempt suicide at least once during their lifetime, and 6% to 19% complete suicide. Risk factors include a family history of suicide, previous suicide attempts, younger age of onset, comorbid psychiatric illnesses, and psychological constructs like hopelessness. Pharmacologic treatment may impact suicidal behaviors, either increasing vulnerability or resilience. Clinicians need to be particularly sensitive to their patient's thoughts and beliefs about death, particularly during stressful times of life or when in a depressive/mixed episode of bipolar disorder. PMID- 26876321 TI - Bipolar Depression and Cognitive Impairment: Shared Mechanisms and New Treatment Avenues. AB - Depression and cognitive impairment are pervasive and highly disabling aspects of bipolar disorder. Although cognitive impairment is partially independent from mood episodes, depressive symptoms may increase the risk of cognitive impairment in bipolar disorder through inflammatory processes as well as health risks such as obesity and sedentary behavior. Novel treatment avenues at the intersection of bipolar depression and cognitive impairment target inflammation directly or indirectly health behaviors such as diet, physical activity, and sleep hygiene. PMID- 26876323 TI - Bipolar Disorder and Inflammation. AB - The pathophysiology of bipolar disorder (BD) remains poorly understood. Current psychopharmacologic treatments are often poorly tolerated and carry high rates of treatment resistance. Mounting evidence has suggested that innate immune system dysfunction may play a role in the pathophysiology of BD. Elevated proinflammatory cytokine levels have been identified. The innate immune system is a novel therapeutic target in BD. Lithium has been shown to have antiinflammatory properties. Further research is needed to establish the role of antiinflammatory agents in the treatment of BD; however, evidence from several clinical trials indicates that antiinflammatory agents may be incorporated into clinical practice soon. PMID- 26876324 TI - Genetics of Bipolar Disorder: Recent Update and Future Directions. AB - Although genetic studies of Bipolar Disorder have been pursued for decades, it has only been in the last several years that clearly replicated findings have emerged. These findings, typically of modest effects, point to a polygenic genetic architecture consisting of multiple common and rare susceptibility variants. While larger genome-wide association studies are ongoing, the advent of whole exome and genome sequencing should lead to the identification of rare, and potentially more penetrant, variants. Progress along both fronts will provide novel insights into the biology of Bipolar Disorder and help usher in a new era of personalized medicine and improved treatments. PMID- 26876325 TI - The Challenge of Bipolar Depression in the 21st Century. PMID- 26876326 TI - Eosinophilic pustular folliculitis: Trends in therapeutic options. PMID- 26876327 TI - Prospective Pilot Study of Mirabegron in Pediatric Patients with Overactive Bladder. AB - BACKGROUND: Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of action (beta3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population. OBJECTIVE: To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics. DESIGN, SETTING, AND PARTICIPANTS: A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. RESULTS AND LIMITATIONS: A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150ml to 200ml (p<0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 (p<0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study. CONCLUSIONS: Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics. PATIENT SUMMARY: We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported. PMID- 26876328 TI - Percutaneous Nephrolithotomy: Update, Trends, and Future Directions. AB - CONTEXT: Percutaneous nephrolithotomy (PCNL) is the surgical standard for treating large or complex renal stones. Since its inception, the technique of PCNL has undergone many modifications. OBJECTIVE: To perform a collaborative review on the latest evidence related to outcomes and innovations in the practice of PCNL since 2000. EVIDENCE ACQUISITION: A literature review was performed using the PubMed database between 2000 and July 2015, restricted to human species, adults, and the English language. The Medline search used a strategy including the following keywords: percutaneous nephrolithotomy, PNL, advances, trends, technique, and the Medical Subject Headings term percutaneous nephrostomy. EVIDENCE SYNTHESIS: Population-based studies have now provided a wealth of information regarding patient outcomes following PCNL. The complexity of the stone treated can be quantified using a variety of validated nephrolithometry classification systems. Increasing familiarity with the supine approach to PCNL has enabled simultaneous combined retrograde and antegrade surgery. Advances such as endoscopic guided percutaneous access may help urologists achieve access with less morbidity. Increasing miniaturization of equipment has led to the development of mini, micro, and ultramini techniques. The tubeless method of PCNL is now accepted practice with good evidence of safety in appropriately selected patients. CONCLUSIONS: Modern-day PCNL allows personalized stone management tailored to individual patient and surgeon factors. Future studies should continue to refine methods to assess complexity and safety and to determine consensus on the use of miniaturized PCNL. PATIENT SUMMARY: Modern-day percutaneous nephrolithotomy has transformed from an operation traditionally undertaken in one position, using one access method with one set of instrumentation and one surgeon, to one with a variety of options at each step. PMID- 26876329 TI - A transmembrane C-type lectin receptor mediates LECT2 effects on head kidney derived monocytes/macrophages in a teleost, Plecoglossus altivelis. AB - Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine involved in many diseases in which immune dysfunction is present. Ayu LECT2 (PaLECT2), which interacts with a C-type lectin receptor (PaCLR), was shown to activate ayu head kidney-derived monocytes/macrophages (MO/MPhi) to improve the outcomes of fish upon bacterial infections. However, it is not known if PaCLR mediates PaLECT2 effects on ayu MO/MPhi. In this study, we determined the role of PaCLR in signal transduction of PaLECT2 on ayu MO/MPhi. We expressed the PaCLR ectodomain in Escherichia coli and produced a refolded recombinant protein (rPaCLR) that was then used to produce the anti-PaCLR IgG (anti-PaCLR) for neutralization. Addition of the refolded PaLECT2 mature peptide (rPaLECT2m) to ayu MO/MPhi cultures, increased cytokine expression, induced chemotaxis, and enhanced phagocytosis and bactericidal activity of these cells were observed. When we added anti-PaCLR to block the ectodomain of PaCLR, these effects were significantly inhibited. Based on our previous works and the data presented here, we conclude that PaCLR mediates the immunomodulatory effects of PaLECT2 on ayu MO/MPhi, thus defining a mechanism by which LECT2 protects fish against pathogens. PMID- 26876330 TI - A preliminary study on the antibacterial mechanism of Tegillarca granosa hemoglobin by derived peptides and peroxidase activity. AB - The blood clam, Tegillarca granosa, is one of the few bivalve molluscs containing hemoglobin (Hb). In the present study, we purified two types of T. granosa hemoglobin, Tg-HbI and Tg-HbII, using size exclusion chromatography and measured their antibacterial and peroxidase activities. We also tested antibacterial activities of peptides prepared by trypsin digestion of purified Tg-Hb and reversed-phase high-performance liquid chromatography purification. Purified Tg HbI and Tg-HbII showed antibacterial activity against Escherichia coli, Pseudomonas putida, Bacillus subtilis, and Bacillus firmus, with differences in minimal inhibitory concentrations (MICs), but lacked antibacterial activity against Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio harveyi and Staphylococcus aureus. In contrast, 7 Tg-Hb derived peptides exhibited varying degrees of antibacterial activity against V. alginolyticus (MICs: 12-200 MUg/ml), V. parahaemolyticus (11-100 MUg/ml) and V. harveyi (1-200 MUg/ml). The antibacterial activity of Hb derived peptides was confirmed by fluorescence microscopy. In addition, peroxidase activity was detected in Tg-HbI and Tg-HbII. The results indicated that in addition to functioning as a respiratory protein T. granosa hemoglobins likely play a role in host antibacterial defense probably via a peroxidase activity of native molecules and some internal peptides released from the proteins. PMID- 26876332 TI - A framework for modeling information propagation of biological systems at critical states. AB - We explore the dynamics of information propagation at the critical state of a biologically inspired system by an individual-based computer model. "Quorum response", a type of social interaction which has been recognized taxonomically in animal groups, is applied as the sole interaction rule among individuals. In the model, we assume a truncated Gaussian distribution to depict the distribution of the individuals' vigilance level. Each individual can assume either a naive state or an alarmed one and only switches from the former state to the latter one. If an individual has turned into an alarmed state, it stays in the state during the process of information propagation. Initially, each individual is set to be at the naive state and information is tapped into the system by perturbing an individual at the boundaries (alerting it to the alarmed state). The system evolves as individuals turn into the alarmed state, according to the quorum response rules, consecutively. We find that by fine-tuning the parameters of the mean and the standard deviation of the Gaussian distribution, the system is poised at a critical state. We present the phase diagrams to exhibit that the parameter space is divided into a super-critical and a sub-critical zone, in which the dynamics of information propagation varies largely. We then investigate the effects of the individuals' mobility on the critical state, and allow a proportion of randomly chosen individuals to exchange their positions at each time step. We find that mobility breaks down criticality of the system. PMID- 26876331 TI - Downregulation of vimentin in macrophages infected with live Mycobacterium tuberculosis is mediated by Reactive Oxygen Species. AB - Mycobacterium tuberculosis persists primarily in macrophages after infection and manipulates the host defence pathways in its favour. 2D gel electrophoresis results showed that vimentin, an intermediate filament protein, is downregulated in macrophages infected with live Mycobacterium tuberculosis H37Rv when compared to macrophages infected with heat- killed H37Rv. The downregulation was confirmed by Western blot and quantitative RT-PCR. Besides, the expression of vimentin in avirulent strain, Mycobacterium tuberculosis H37Ra- infected macrophages was similar to the expression in heat-killed H37Rv- infected macrophages. Increased expression of vimentin in H2O2- treated live H37Rv-infected macrophages and decreased expression of vimentin both in NAC and DPI- treated heat-killed H37Rv infected macrophages showed that vimentin expression is positively regulated by ROS. Ectopic expression of ESAT-6 in macrophages decreased both the level of ROS and the expression of vimentin which implies that Mycobacterium tuberculosis mediated downregulation of vimentin is at least in part due to the downregulation of ROS by the pathogen. Interestingly, the incubation of macrophages with anti vimentin antibody increased the ROS production and decreased the survival of H37Rv. In addition, we also showed that the pattern of phosphorylation of vimentin in macrophages by PKA/PKC is different from monocytes, emphasizing a role for vimentin phosphorylation in macrophage differentiation. PMID- 26876333 TI - Spin dynamics and relaxation in graphene dictated by electron-hole puddles. AB - The understanding of spin dynamics and relaxation mechanisms in clean graphene, and the upper time and length scales on which spin devices can operate, are prerequisites to realizing graphene-based spintronic technologies. Here we theoretically reveal the nature of fundamental spin relaxation mechanisms in clean graphene on different substrates with Rashba spin-orbit fields as low as a few tens of MUeV. Spin lifetimes ranging from 50 picoseconds up to several nanoseconds are found to be dictated by substrate-induced electron-hole characteristics. A crossover in the spin relaxation mechanism from a Dyakonov Perel type for SiO2 substrates to a broadening-induced dephasing for hBN substrates is described. The energy dependence of spin lifetimes, their ratio for spins pointing out-of-plane and in-plane, and the scaling with disorder provide a global picture about spin dynamics and relaxation in ultraclean graphene in the presence of electron-hole puddles. PMID- 26876334 TI - Detection of Brownian Torque in a Magnetically-Driven Rotating Microsystem. AB - Thermal fluctuations significantly affect the behavior of microscale systems rotating in shear flow, such as microvortexes, microbubbles, rotating micromotors, microactuators and other elements of lab-on-a-chip devices. The influence of Brownian torque on the motion of individual magnetic microparticles in a rotating magnetic field is experimentally determined using optical tweezers. Rotational Brownian motion induces the flattening of the breakdown transition between the synchronous and asynchronous modes of microparticle rotation. The experimental findings regarding microparticle rotation in the presence of Brownian torque are compared with the results of numerical Brownian dynamics simulations. PMID- 26876336 TI - Electric Field-Assisted Photochemical Water Splitting Should Operate with 287 nm Light. AB - The major photoreaction of water is the homolytic splitting of one O-H bond starting from the 1(1) B1 excited state (lambdamax = 167 nm). This reaction produces H* and *OH radicals. The combination of two H* atoms leads to the potential energy carrier dihydrogen. However, the energy required to obtain the photoreactive 1(1) B1 electronic state is about 7.4 eV, which cannot be effectively provided by solar radiation. The sun light spectrum on earth comprises the visible and ultraviolet region, but shows vanishing intensity near 7 eV (177.1 nm). This work provides theoretical evidence that the photoreactive 1(1) B1 state of water can be shifted into the ultraviolet (UV-B) light region (~287 nm) by including explicitly an electric field in the calculations of the water absorption spectrum. To accomplish such bathochromic shift, a large field strength of 3.08 VA(-1) is required. The field-dependent excitation energies were calculated by applying the symmetry-adapted cluster configuration interaction (SAC-CI) procedure. Based on this theoretical analysis, we propose that photochemical water splitting can be accomplished by means of 287 nm light provided the water molecule is favorably oriented by an external electric field and is subsequently activated by a reversal of the field orientation. PMID- 26876335 TI - Rigor and replication in time-frequency analyses of cognitive electrophysiology data. AB - Cognitive electrophysiology is a subfield of neuroscience that focused on linking M/EEG data to aspects of cognition and the neurophysiological processes that produce them. This field is growing in terms of the novelty and sophistication of findings, data, and data analysis methods. Simultaneously, many areas of modern sciences are experiencing a "replication crisis," prompting discussions of best practices to produce robust and replicable research. The purpose of this paper is to contribute to this discussion with a particular focus on cognitive electrophysiology. More issues are raised than are answered. Several recommendations are made, including (1) incorporate replications into new experiments, (2) write clear Methods and Results sections, and (3) publish null results. PMID- 26876337 TI - Prevalence of mutations in HBV DNA polymerase gene associated with nucleos(t)ide resistance in treatment-naive patients with Chronic Hepatitis B in Central China. AB - OBJECTIVE: There are a lot of disagreements in the studies on hepatitis B virus (HBV) DNA polymerase mutation rate associated with nucleos(t)ide analogues (NAs) in treatment-naive chronic hepatitis B (CHB) patients. This is the first study aimed to investigate the prevalence of spontaneous HBV resistance mutations in Central China. METHODS: This study included treatment-naive patients with CHB from June 2012 to May 2015 receiving care at the Institute of Liver Disease in Central China. All patients completed a questionnaire covering different aspects, such as family medical history, course of liver disease, medication history, alcohol use, among others. Mutations in HBV DNA polymerase associated with NAs resistance were detected using INNO-LiPA assay. RESULTS: 269 patients were infected with HBV genotype B (81.4%), C (17.9%), and both B and C (0.7%). Mutations in HBV DNA polymerase were detected in 24 patients (8.9%) including rtM204I/V (n=6), rtN236T (n=5), rtM250V (n=2), rtL180M (n=2), rtT184G (n=1), rtM207I (n=1), rtS202I (n=1), rtM204V/I & rtL180M (n=5), and rtM204I & rtM250V (n=1). CONCLUSION: Spontaneous HBV resistance mutations in HBV DNA polymerase were found in treatment-naive patients with CHB in Central China. These findings suggest that we should analyze HBV DNA polymerase resistance mutation associated with NAs before giving antiviral therapy such as lamivudine (LAM), adefovir (ADV), and telbivudine (LdT). PMID- 26876338 TI - Molecular epidemiology of Pseudomonas aeruginosa clinical isolates. PMID- 26876339 TI - Ghostbusting-taking the sheet off the ghost. PMID- 26876340 TI - Results of Open Surgical Repair in Patients With Marfan Syndrome and Distal Aortic Dissection. AB - BACKGROUND: In patients with Marfan syndrome (MFS), distal aortic dissection can necessitate thoracoabdominal aortic aneurysm (TAAA) repair in survivors of acute DeBakey type I dissection and those with DeBakey type III dissection. We examined outcomes of surgical repair of TAAA in patients with MFS with distal aortic dissection. METHODS: Data were analyzed for 127 consecutive TAAA repairs performed between January 2004 and June 2014 in patients with MFS and distal aortic dissection-DeBakey types I (n = 73) and III (n = 54). The median time from dissection onset to TAAA repair was 5.2 years (interquartile range [IQR]: 2.1 to 9.8 years) for the overall group and was longer in patients with DeBakey I (6.5 years, IQR: 3.5 to 13.9 years) than patients with DeBakey III (2.9 years, IQR: 0.6 to 6.0 years, p < 0.001). Eleven patients (9%) had acute or subacute dissection at the time of repair. Sixty-six patients (52%) underwent Crawford extent II TAAA repair. A composite end point, adverse event, was defined as operative death or permanent stroke, renal failure, paraplegia, or paraparesis. RESULTS: Eight patients had adverse events (6%), including 5 operative deaths (4%). There was no permanent stroke and 1 case each of permanent paraplegia and paraparesis. At discharge, 2 early survivors (2%) had renal failure. Extent II repairs did not have substantially different outcomes from other repairs. CONCLUSIONS: In these patients with MFS with aortic dissection, open TAAA repair incurred reasonable operative risk, but improvements are needed to reduce rates of renal failure. Extent II TAAA repair does not appear to increase operative risk in patients with MFS. PMID- 26876341 TI - Use of One-Way Intrabronchial Valves in Air Leak Management After Tube Thoracostomy Drainage. AB - BACKGROUND: A persistent air leak represents significant clinical management problems, potentially affecting morbidity, mortality, and health care costs. In 2008, a unidirectional, intrabronchial valve received humanitarian device exemption for use in managing prolonged air leak after pulmonary resection. Since its introduction, numerous reports exist but no large series describe current utilization or outcomes. Our aim was to report current use of intrabronchial valves for air leaks and review outcome data associated with its utilization. METHODS: A multicenter, retrospective review of intrabronchial valve utilization from January 2013 to August 2014 was performed at eight centers. Data regarding demographics, valve utilization, and outcomes were analyzed. RESULTS: We identified 112 patients undergoing evaluation for intrabronchial valve placement, with 67% (75 of 112) undergoing valve implantation. Nearly three quarters of patients underwent valve placement for off-label usage (53 of 75). A total of 195 valves were placed in 75 patients (mean 2.6 per patient; range, 1 to 8) with median time to air leak resolution of 16 days (range, 2 to 156). CONCLUSIONS: We present the largest, multicenter study of patients undergoing evaluation for intrabronchial valve use for air leak management. Our data suggest the majority of intrabronchial valve placements are occurring for off-label indications. Although the use of intrabronchial valves are a minimally invasive intervention for air leak management, the lack of rigorously designed studies demonstrating efficacy remains concerning. Prospective randomized controlled studies remain warranted. PMID- 26876342 TI - Community-Based Multidisciplinary Computed Tomography Screening Program Improves Lung Cancer Survival. AB - BACKGROUND: Lung cancer is the most common cause of cancer deaths in the United States. Overall survival is less than 20%, with the majority of patients presenting with advanced disease. The National Lung Screening Trial, performed mainly in academic medical centers, showed that cancer mortality can be reduced with computed tomography (CT) screening compared with chest radiography in high risk patients. To determine whether this survival advantage can be duplicated in a community-based multidisciplinary thoracic oncology program, we initiated a CT scan screening program for lung cancer within an established health care system. METHODS: In 2008, we launched a lung cancer CT screening program within the WellStar Health System (WHS) consisting of five hospitals, three health parks, 140 outpatient medical offices, and 12 imaging centers that provide care in a five-county area of approximately 1.4 million people in Metro-Atlanta. Screening criteria incorporated were the International Early Lung Cancer Action Program (2008 to 2010) and National Comprehensive Cancer Network guidelines (2011 to 2013) for moderate- and high-risk patients. RESULTS: A total of 1,267 persons underwent CT lung cancer screening in WHS from 2008 through 2013; 53% were men, 87% were 50 years of age or older, and 83% were current or former smokers. Noncalcified indeterminate pulmonary nodules were found in 518 patients (41%). Thirty-six patients (2.8%) underwent a diagnostic procedure for positive findings on their CT scan; 30 proved to have cancer, 28 (2.2%) primary lung cancer and 2 metastatic cancer, and 6 had benign disease. Fourteen patients (50%) had their lung cancer discovered on their initial CT scan, 11 on subsequent scans associated with indeterminate pulmonary nodules growth and 3 patients who had a new indeterminate pulmonary nodules. Only 15 (54%) of these 28 patients would have qualified as a National Lung Screening Trial high-risk patient; 75% had stage I or II disease. Overall 5-year survival was 64% and 5-year cancer specific survival was 71% in the screened patients, whereas nonscreened lung cancer patients during that time in WHS had an overall survival of only 19% (p < 0.001). CONCLUSIONS: A community-based multidisciplinary lung cancer screening program can improve survival of patients with lung cancer outside of a large multicenter study. This survival advantage was caused by a significant stage shift to earlier disease. Lung cancer CT screening may also benefit patients not meeting the National Lung Screening Trial criteria who are at moderate or high risk for lung cancer. PMID- 26876343 TI - Relationship of Intraoperative Transit Time Flowmetry Findings to Angiographic Graft Patency at Follow-Up. AB - Early and late graft occlusion remains a significant complication of coronary artery bypass grafting. Transit time flowmetry is the most commonly used imaging technique to assess graft patency intraoperatively. Although the value of transit time flowmetry for intraoperative quality control of coronary anastomosis is well established, its standard variables for predicting eventual graft failure remain controversial. This review readdresses the issue of intraoperative transit time flowmetry, with a particular emphasis on defining cutoff values for standard variables and correlating them with the ability to predict midterm and long-term graft patency for arterial and venous conduits. Further research is warranted to support clinically useful recommendations on the intraoperative application and interpretation of transit time flowmetry. PMID- 26876345 TI - Nurses Count: Tracking Performance to Improve Cesarean Delivery Rates. PMID- 26876344 TI - Feminization and masculinization of western mosquitofish (Gambusia affinis) observed in rivers impacted by municipal wastewaters. AB - Municipal wastewaters have been known to contain various estrogens and androgens. Little is known about the joint action of these chemicals from wastewaters on fishes in the aquatic environment. The objectives of this study were to investigate the estrogenic and/or androgenic effects in wild mosquitofish (Gambusia affinis) of two effluent-impacted rivers in South China by determining morphological changes and hepatic mRNA expression levels of relevant genes such as vitellogenin (Vtg), estrogen receptor (ERalpha) and androgen receptors (ARalpha and ARbeta), and to assess the linkages of those morphological changes and hepatic mRNA expression levels to the chemical concentrations measured by in vitro bioassays and chemical analysis. The results showed a significant induction of Vtg and ERalpha mRNA in the livers of the males and a gonopodium-like anal fin in the females collected at the majority of sites. Redundancy analysis and Pearson correlation analysis showed that the chemical concentrations obtained by in vitro bioassays and chemical analysis had significant correlations with some of the endpoints for the estrogenic and/or androgenic effects in mosquitofish. The findings from this study indicate that the estrogens and androgens present in the two rivers could cause the observed estrogenic and androgenic effects in mosquitofish. PMID- 26876346 TI - Particulate matter induces prothrombotic microparticle shedding by human mononuclear and endothelial cells. AB - Particulate airborne pollution is associated with increased cardiopulmonary morbidity. Microparticles are extracellular vesicles shed by cells upon activation or apoptosis involved in physiological processes such as coagulation and inflammation, including airway inflammation. We investigated the hypothesis that particulate matter causes the shedding of microparticles by human mononuclear and endothelial cells. Cells, isolated from the blood and the umbilical cords of normal donors, were cultured in the presence of particulate from a standard reference. Microparticles were assessed in the supernatant as phosphatidylserine concentration. Microparticle-associated tissue factor was assessed by an one-stage clotting assay. Nanosight technology was used to evaluate microparticle size distribution. Particulate matter induces a dose- and time- dependent, rapid (1h) increase in microparticle generation in both cells. These microparticles express functional tissue factor. Particulate matter increases intracellular calcium concentration and phospholipase C inhibition reduces microparticle generation. Nanosight analysis confirmed that upon exposure to particulate matter both cells express particles with a size range consistent with the definition of microparticles (50-1000 nm). Exposure of mononuclear and endothelial cells to particulate matter upregulates the generation of microparticles at least partially mediated by calcium mobilization. This observation might provide a further link between airborne pollution and cardiopulmonary morbidity. PMID- 26876347 TI - Sample pre-concentration with high enrichment factors at a fixed location in paper-based microfluidic devices. AB - The lack of sensitivity is a major problem among microfluidic paper-based analytical devices (MUPADs) for early disease detection and diagnosis. Accordingly, the present study presents a method for improving the enrichment factor of low-concentration biomarkers by using shallow paper-based channels realized through a double-sided wax-printing process. In addition, the enrichment factor is further enhanced by exploiting the ion concentration polarization (ICP) effect on the cathodic side of the nanoporous membrane, in which a stationary sample plug is obtained. The occurrence of ICP on the shallow-channel MUPAD is confirmed by measuring the current-voltage response as the external voltage is increased from 0 to 210 V (or the field strength from 0 to 1.05 * 10(4) V m(-1)) over 600 s. In addition, to the best of our knowledge, the electroosmotic flow (EOF) speed on the MUPAD fabricated with a wax-channel is measured for the first time using a current monitoring method. The experimental results show that for a fluorescein sample, the concentration factor is increased from 130-fold in a conventional full-thickness paper channel to 944-fold in the proposed shallow channel. Furthermore, for a fluorescein isothiocyanate-labeled bovine serum albumin (FITC-BSA) sample, the proposed shallow-channel MUPAD achieves an 835 fold improvement in the concentration factor. The concentration technique presented here provides a novel strategy for enhancing the detection sensitivity of MUPAD applications. PMID- 26876349 TI - Immediate Single-Tooth Implant Placement in Bony Defects in the Esthetic Zone: A 1-Year Randomized Controlled Trial. AB - BACKGROUND: This study aims to assess, with regard to marginal bone level (MBL), whether the outcome of immediate implant placement in bony defects in the esthetic zone was non-inferior to delayed implant placement after 1 year. METHODS: Forty patients with a failing tooth in the esthetic zone and a labial bony defect of >=5 mm after removal of a tooth were randomly assigned for immediate (n = 20) or delayed (n = 20) implant placement. Second-stage surgery and provisionalization occurred after 3 months of healing. Follow-up was at 1 month and 1 year after definitive crown placement. The study was powered to detect a difference in MBL of >0.9 mm. Buccal bone thickness, soft tissue peri implant parameters, esthetic indices, and patient satisfaction were also assessed. RESULTS: One year after definitive crown placement, MBL loss was 0.56 +/- 0.39 mm mesially and 0.74 +/- 0.51 mm distally for the immediate placement group and 0.51 +/- 0.43 mesially and 0.54 +/- 0.45 distally mm for the delayed placement group, respectively (not significant). Regarding differences in means, non-inferiority was observed after 1 year (difference in mean for immediate versus delayed: mesially 0.04 mm [95% confidence interval (CI) = -0.22 to 0.30 mm, P = 0.40]; distally 0.21 mm [95% CI = -0.10 to 0.51 mm, P = 0.58]). No significant differences in the other outcome variables were observed. CONCLUSIONS: Immediate implant placement with delayed provisionalization was non inferior to delayed implant placement with delayed provisionalization in labial bony defects of >=5 mm regarding change in MBL. Although not powered for other outcome variables, no clinically relevant differences were observed in these variables. PMID- 26876350 TI - Aggregatibacter actinomycetemcomitans-Induced AIM2 Inflammasome Activation Is Suppressed by Xylitol in Differentiated THP-1 Macrophages. AB - BACKGROUND: Aggressive periodontitis is characterized by rapid destruction of periodontal tissue caused by Aggregatibacter actinomycetemcomitans. Interleukin (IL)-1beta is a proinflammatory cytokine, and its production is tightly regulated by inflammasome activation. Xylitol, an anticaries agent, is anti-inflammatory, but its effect on inflammasome activation has not been researched. This study investigates the effect of xylitol on inflammasome activation induced by A. actinomycetemcomitans. METHODS: The differentiated THP-1 macrophages were stimulated by A. actinomycetemcomitans with or without xylitol and the expressions of IL-1beta and inflammasome components were detected by real time PCR, ELISA, confocal microscopy and Immunoblot analysis. The effects of xylitol on the adhesion and invasion of A. actinomycetemcomitans to cells were measured by viable cell count. RESULTS: A. actinomycetemcomitans increased pro IL-1beta synthesis and IL-1beta secretion in a multiplicity of infection- and time dependent manner. A. actinomycetemcomitans also stimulated caspase-1 activation. Among inflammasome components, apoptosis-associated speck-like protein containing a CARD (ASC) and absent in melanoma 2 (AIM2) proteins were upregulated by A. actinomycetemcomitans infection. When cells were pretreated with xylitol, proIL 1beta and IL-1beta production by A. actinomycetemcomitans infection was significantly decreased. Xylitol also inhibited ASC and AIM2 proteins and formation of ASC puncta. Furthermore, xylitol suppressed internalization of A. actinomycetemcomitans into differentiated THP-1 macrophages without affecting viability of A. actinomycetemcomitans within cells. CONCLUSIONS: A. actinomycetemcomitans induced IL-1beta production and AIM2 inflammasome activation. Xylitol inhibited these effects, possibly by suppressing internalization of A. actinomycetemcomitans into cells. Thus, this study proposes a mechanism for IL-1beta production via inflammasome activation and discusses a possible use for xylitol in periodontal inflammation caused by A. actinomycetemcomitans. PMID- 26876348 TI - A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. AB - Embryonic stem cells (ESCs) represent a transient biological state, where pluripotency is coupled with fast proliferation. ESCs display a constitutively active DNA damage response (DDR), but its molecular determinants have remained elusive. Here we show in cultured ESCs and mouse embryos that H2AX phosphorylation is dependent on Ataxia telangiectasia and Rad3 related (ATR) and is associated with chromatin loading of the ssDNA-binding proteins RPA and RAD51. Single-molecule analysis of replication intermediates reveals massive ssDNA gap accumulation, reduced fork speed and frequent fork reversal. All these marks of replication stress do not impair the mitotic process and are rapidly lost at differentiation onset. Delaying the G1/S transition in ESCs allows formation of 53BP1 nuclear bodies and suppresses ssDNA accumulation, fork slowing and reversal in the following S-phase. Genetic inactivation of fork slowing and reversal leads to chromosomal breakage in unperturbed ESCs. We propose that rapid cell cycle progression makes ESCs dependent on effective replication-coupled mechanisms to protect genome integrity. PMID- 26876351 TI - Crevicular Fluid Growth Factors Release Profile Following the Use of Platelet Rich Fibrin and Plasma Rich Growth Factors in Treating Periodontal Intrabony Defects: A Randomized Clinical Trial. AB - BACKGROUND: The open, usually contaminated nature of periodontal defects could negatively affect availability and activity of platelet concentrate-suggested growth factors (GF). The aim of this study is to test this hypothesis and investigate concentrations of: 1) vascular endothelial growth factor (VEGF) and 2) platelet-derived growth factor (PDGF-BB) in gingival crevicular fluid (GCF) from localized intrabony defects treated with platelets rich in growth factors (PRGF) or platelet-rich fibrin (PRF) compared with a control xenograft defect filling. METHODS: Thirty non-smoking patients suffering severe chronic periodontitis were allocated to this randomized, prospective, single-masked trial. Each patient had one interproximal defect randomly distributed to: 1) group 1: bone-substitute grafting control (n = 10); 2) group 2: experimental PRGF (n = 10); or 3) group 3: PRF (n = 10). Clinical parameters were measured at baseline and 6 and 9 months following therapy. GCF samples were obtained on days 1, 3, 7, 14, 21, and 30 after therapy for evaluation of VEGF and PDGF-BB levels. RESULTS: On days 1, 3, and 7 following surgery, mean levels of VEGF and PDGF-BB at sites treated with PRGF and PRF were not significantly different versus the control. Levels of PDGF-BB and VEGF were higher in the PRGF-treated group, but differences were not significant. Growth factor levels decreased significantly in samples collected on days 14, 21, and 30 with non-significant differences among the three groups. No significant clinical differences were reported among the three groups during the two observation periods (early period: days 1, 3, and 7; and later period: days 14, 21, and 30). CONCLUSIONS: Within the limits of the present study, it can be concluded that PRF and PRGF platelet concentrate failed to augment clinical effects achieved with the xenograft alone in treating intrabony defects. Periodontal defects could not retain extraphysiologic levels of GF suggested to be associated with platelet concentrate. PMID- 26876352 TI - Cone-Beam Computed Tomography for Detection of Intrabony and Furcation Defects: A Systematic Review Based on a Hierarchical Model for Diagnostic Efficacy. AB - BACKGROUND: The aim of this review is to assess the diagnostic efficacy of cone beam computed tomography (CBCT) for the diagnosis of and/or treatment planning for intrabony and furcation defects, using a well-known six-tiered hierarchical model for diagnostic efficacy. METHODS: The MEDLINE, EMBASE, and Cochrane Library bibliographic databases were searched until August 2015 for studies evaluating CBCT imaging for the diagnosis of and/or treatment planning for intrabony and/or furcation defects. The search strategy was restricted to English language publications using the combination of MeSH terms, free terms, and key words. RESULTS: The search strategy yielded 16 publications that qualitatively or quantitatively evaluated the use of CBCT for the detection of intrabony and/or furcation defects and how CBCT influenced the diagnosis and/or treatment plan. According to Quality Assessment of Studies of Diagnostic Accuracy-2, all included studies were medium to low risk of bias. The review identified only one study that investigated the societal efficacy, and none evaluated the patient outcome efficacy or therapeutic efficacy. One study investigated the diagnostic thinking efficacy. All other included studies investigated the diagnostic accuracy of CBCT. CONCLUSIONS: From the assessed studies, it can be concluded that there is not sufficient scientific evidence to justify the use of CBCT for the diagnosis of and/or treatment planning for intrabony and furcation defects. Furthermore, the effectiveness of CBCT for such diagnostic tasks has been assessed only at low diagnostic efficacy levels. PMID- 26876354 TI - Comparative analysis of innate immune responses to Streptococcus phocae strains in Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). AB - Streptococcus phocae subsp. salmonis is a Gram-positive bacterium that causes mortality only in Atlantic salmon (Salmo salar) farmed in Chile, even when this species is co-cultured with rainbow trout (Oncorhynchus mykiss). This susceptibility could be determined by innate immune response components and their responses to bacterial infection. This fish pathogen shares subspecies status with Streptococcus phocae subsp. phocae isolated from seals. The present study compared innate immune system mechanisms in Atlantic salmon and rainbow trout when challenged with different S. phocae, including two isolates from Atlantic salmon (LM-08-Sp and LM-13-Sp) and two from seal (ATCC 51973(T) and P23). Streptococcus phocae growth was evaluated in the mucus and serum of both species, with rainbow trout samples evidencing inhibitory effects. Lysozyme activity supported this observation, with significantly higher (p < 0.01) expression in rainbow trout serum and mucus as compared to Atlantic salmon. No differences were found in phagocytic capacity between fish species when stimulated with ATCC 51973(T) and P23. Against all S. phocae strains, rainbow trout and Atlantic salmon showed up to two-fold increased bactericidal activity, and rainbow trout demonstrated up to three-fold greater reactive oxygen species production in macrophages. In conclusion, the non-specific humoral and cellular barriers of Atlantic salmon were immunologically insufficient against S. phocae subsp. salmonis, thereby facilitating streptococcosis. Moreover, the more robust response of rainbow trout to S. phocae could not be attributed to any specific component of the innate immune system, but was rather the consequence of a combined response by the evaluated components. PMID- 26876355 TI - Molecular cloning and functional analysis of nucleotide-binding oligomerization domain-containing protein 1 in rainbow trout, Oncorhynchus mykiss. AB - NOD1 has important roles in innate immunity as sensor of microbial components derived from bacterial peptidoglycan. In this study, we identified genes encoding components of the NOD1 signaling pathway, including NOD1 (OmNOD1) and RIP2 (OmRIP2) from rainbow trout, Oncorhynchus mykiss, and investigated whether OmNOD1 has immunomodulating activity in a rainbow trout hepatoma cell line RTH-149 treated with NOD1-specific ligand (iE-DAP). The deduced amino acid sequence of OmNOD1 contained conserved CARD, NOD and LRR domains. Loss-of-function and gain of-function experiments indicated that OmNOD1 is involved in the expression of pro-inflammatory cytokines. Silencing of OmNOD1 in RTH-149 cells treated with iE DAP decreased the expression of IL-1beta, IL-6, IL-8 and TNF-alpha. Conversely, overexpression of OmNOD1 resulted in up-regulation of IL-1beta, IL-6, IL-8 and TNF-alpha expression. In addition, RIP2 inhibitor (gefitinib) significantly decreased the expression of these pro-inflammatory cytokines induced by iE-DAP in RTH-149 cells. These findings highlight the important role of NOD1 signaling pathway in fish in eliciting innate immune response. PMID- 26876356 TI - Heat-killed whole-cell products of the probiotic Pseudomonas aeruginosa VSG2 strain affect in vitro cytokine expression in head kidney macrophages of Labeo rohita. AB - Present study was undertaken to investigate the efficiency of heat-killed whole cell products (HKWCPs) of probiotic Pseudomonas aeruginosa VSG2 strain in stimulating the cytokine responses in the head kidney (HK) macrophages of Labeo rohita. The HK macrophages were incubated with HKWCPs or lipopolysaccharide (LPS), and the responses of cytokine genes, namely interleukin-10 (IL-10), IL 1beta, IL-p35, IL-12p40, tumour necrosis factor-alpha (TNF-alpha), nuclear factor kappa B (NF-kappaB), cyclooxygenase-2 (COX-2), interferon-alpha (IFN-alpha), and interferon-gamma (IFN-gamma) were assessed by quantitative real-time PCR (qRT PCR) at 2, 8, 16, 24, 48, 72 h post-stimulation (hps). Among proinflammatory cytokines, significantly higher expression of IL-1beta and TNF-alpha was observed at 8-24 hps, and 2-16 hps with HKWCPs, respectively, as compared to controls. However, COX-2 and NF-kappaB displayed strong expression (P < 0.05) at 2-8 hps, and 8, 16 and 72 hps with HKWCPs, respectively. Antiviral cytokines IFN-alpha and IFN-gamma displayed strong expression (P < 0.05) at 8-24 hps, and 2, 24 and 48 hps with HKWCPs, respectively. Expressions of cell-mediated immune factor genes (IL-12p35 and IL-12p40) were also significantly upregulated at various time points, except IL-12p40 at 72 hps, in HK macrophages stimulated with HKWCPs. Expression of the anti-inflammatory cytokine IL-10 was upregulated (P < 0.05) at 2-24 hps HKWCPs, compared to controls. Enhanced cellular (phagocytic activity and superoxide anion production) and humoral (lysozyme) immune parameters of treated HK macrophages confirmed the induction of inflammatory response. Thus, our results indicated that HKWCPs of probiotic P. aeruginosa VSG2 had greater potential for stimulating the in vitro expression of cytokines in fish and that these HKWCPs may be used as vaccine adjuvants in aquaculture. PMID- 26876357 TI - Abundant members of Scavenger receptors family and their identification, characterization and expression against Vibrio alginolyticus infection in juvenile Larimichthys crocea. AB - Scavenger receptors (SRs) are crucial pattern recognition receptors (PRRs) to defense pathogen infection in fish innate immunity. In this paper, some members in SRs family of Larimichthys crocea were identified, including eight genes in the class A, B, D and F families. (G + C) % of all SRs members held 51% ~ 59%, and these genes were no obvious codon bias by analyzing the distribution of A-, T , G- and C-ended codons. The order of Enc for all SRs members by sequencing was LycCD68 > LycSCARA5 > LycSCARB1 > LycCD163 > LycMARCO > LycSREC1 > LycSCARA3 > LycSREC2. Moreover, different lengths and numbers of exons and introns led to the diverse mRNAs and respective functional domains or motifs, for example, an optional cysteine-rich (SRCR) domain in LycMARCO and LycSCARA5, an epidermal growth factor (EGF) and EGF-like domain in LycSREC1 and LycSREC2. The sub cellular localization demonstrated SRs members mainly located in plasma membrane or extracellular matrix. Further, all of the SRs members in L. crocea were almost low expressed in heart, gill and intestine, whereas high in spleen and liver. After stimulation by Vibrio alginolyticus, the class A and F families were induced significantly, but the class B and D families expressed less even none after pathogenic infection. All the findings would pave the way to understand not only the evolution of the SR-mediated immune response, but also the complexity of fish immunity. PMID- 26876358 TI - Piscidin: Antimicrobial peptide of rock bream, Oplegnathus fasciatus. AB - The piscidin family consists of antimicrobial peptides (AMPs) that are mainly found in fish and are crucial effectors of fish innate immune responses. The piscidin family typically has broad-spectrum antimicrobial activity and can modulate immune responses. In this study, we cloned rock bream piscidin (Rbpisc) and investigated its gene expression and biological activity (including antimicrobial and cytotoxic activities). The coding region of Rbpisc consisted of 213 base pairs (bp) encoding 70 amino acid residues. The tertiary structure predicted for Rbpisc includes an amphipathic helix-loop-helix structure. The Rbpisc gene was highly expressed in the gills of healthy fish. The gene expression of Rbpisc increased in the gills after pathogen infection, while the expression was down-regulated in other tissues. A synthetic peptide based on the AMP 12 domain amino acid sequence of Rbpisc appeared to have broad-spectrum antimicrobial activity against various bacteria. However, the synthetic peptide exhibited weak haemolytic activity against fish erythrocytes. These results suggest that Rbpisc might play an important role in the innate immune responses of rock bream. PMID- 26876359 TI - Assessment of salivary total antioxidant capacity in patients with primary untreated head and neck squamous cell carcinoma with ORAC. AB - BACKGROUND: Oxidative DNA damage leads to abnormalities in endogenous cellular processes and constitutes a direct link between free radicals, antioxidants and squamous cell carcinoma (SCC). Oxygen radical absorbance capacity (ORAC) method is used to measure antioxidant capacity versus oxygen free radicals. There is no report on the application of ORAC to evaluate salivary antioxidant capacity in patients with head and neck SCC. This study investigated the relation between total antioxidant capacity of saliva, measured with ORAC method, and the incidence, location, size and histopathological grading of SCC. METHODS: Salivary antioxidant capacity was assessed in 30 male and female patients with histopathologically confirmed oral and laryngeal SCC. Histopathological grading of SCC was based on WHO classification. RESULTS: Mean ORAC in patients with SCC was higher than the mean value in the control group. Statistically significant difference was observed in the study group versus the control group. No significant differences were observed for ORAC values in relation to histopathological grading, tumour size and spread to lymph nodes. CONCLUSIONS: The obtained results can advocate local compensatory mechanism in saliva in response to increased oxidative stress associated with primary tumour. ORAC can become an additional factor in head and neck SCC prognosis, but further investigation is required. PMID- 26876360 TI - The Possibilities of Reducing Food Choice to Improve the Performance of College Foodservices. AB - BACKGROUND: College administrative and management leaders, foodservice personnel, and student residents value social, nutritional, financial, and environmental sustainability in their dining expectations. Menu choice reduction looks promising as a strategy to achieve these goals. However, foodservice research about dominant attitudes across these stakeholders is limited. OBJECTIVE: To identify qualitative views from all stakeholders about choice reduction to ensure that any changes to the meal service are not to the detriment of consumer satisfaction. DESIGN: A comprehensive list of 74 statements representing the spectrum of attitudes surrounding choice was generated by searching a variety of resources, including academic literature and Internet sites, and by conducting semistructured interviews with stakeholders. A final set of 42 statements resulted from researcher scrutiny for optimum balance, clarity, appropriateness, simplicity, and applicability. A new sample of participants was then asked to sort these 42 statements into a normal distribution grid from "strongly disagree" to "strongly agree." PARTICIPANTS/SETTING: A purposive convenience sample of stakeholders (staff n=5 and residents n=4) was used to identify statements about choice reduction. A second sample of stakeholders (staff n=6 and residents n=29) were recruited to sort the final 42 statements. STATISTICAL ANALYSES PERFORMED: Q methodology analysis techniques were used. This involved conducting a by-person factor analysis, using the centroid factor extraction method because of the permissiveness it allows for data exploration. A varimax factor rotation to enhance interpretability of the results identified shared viewpoints. RESULTS: Three dominant viewpoints toward the possibility of choice reduction in the meal service were identified. Factor 1 was "health driven" (in which healthiness was paramount). Factor 2 was "variety seekers" (in which choice had instrumental value). Factor 3 was "choice lovers" (in which choice had intrinsic value). CONCLUSIONS: Although participants could see a number of benefits of choice reduction, strong attitudinal barriers existed toward adopting choice reduction initiatives. These barriers need to be overcome to avoid dissatisfaction with the foodservice should choice reduction measures be implemented. PMID- 26876361 TI - Two chiroptical modes of silver nanospirals. AB - As an emerging three-dimensional chiral metamaterial, plasmonic nanospirals (NSs) possess inherent chiroptical activity that has attracted increasing attention for developing potential photonic applications. However, the study of chiroptical activity of plasmonic NSs is still in its infancy, especially for NSs made of silver, which is a typical plasmonic material with high plasmonic quality. Herein, we present a systematic study of circular dichroism (CD) of silver NSs (AgNSs) that are fabricated and engineered in helical lengths by glancing-angle deposition (GLAD) and dispersed in ethanol. The CD spectrum is composed of a bisignated mode of two peaks, one in the UV regime and the other in the visible. The UV mode has a resonance wavelength saturating at ~375 nm and a linewidth decoupled from the helical elongation, while the visible mode tends to have a redshift and its linewidth broadens linearly with the elongation of AgNS. Helical elongation generally amplifies the chiroptical activity of both modes. Finite element simulation shows good agreement with the experimental CD results, and accounts for the wavelength-related chiroptical distinction in terms of the resonance wavelength. This work contributes to understanding the bisignated chiroptical responses of plasmonic nanospirals, and introduces a simple method to tailor the visible chiroptical activity that is strongly desired to explore a wide range of chirality-related bio-applications. PMID- 26876353 TI - Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis. AB - Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models. PMID- 26876362 TI - Superconductivity in Ta3Pd3Te14 with quasi-one-dimensional PdTe2 chains. AB - We report bulk superconductivity at 1.0 K in a low-dimensional ternary telluride Ta3Pd3Te14 containing edge-sharing PdTe2 chains along crystallographic b axis, similar to the recently discovered superconductor Ta4Pd3Te16. The electronic heat capacity data show an obvious anomaly at the transition temperature, which indicates bulk superconductivity. The specific-heat jump is DeltaC/(gamma(n)T(c)) ~ 1.35, suggesting a weak coupling scenario. By measuring the low-temperature thermal conductivity, we conclude that Ta3Pd3Te14 is very likely a dirty s-wave superconductor. The emergence of superconductivity in Ta3Pd3Te14 with a lower T(c), compared to that of Ta4Pd3Te16, may be attributed to the lower density of states. PMID- 26876363 TI - Fashioning the Face: Sensorimotor Simulation Contributes to Facial Expression Recognition. AB - When we observe a facial expression of emotion, we often mimic it. This automatic mimicry reflects underlying sensorimotor simulation that supports accurate emotion recognition. Why this is so is becoming more obvious: emotions are patterns of expressive, behavioral, physiological, and subjective feeling responses. Activation of one component can therefore automatically activate other components. When people simulate a perceived facial expression, they partially activate the corresponding emotional state in themselves, which provides a basis for inferring the underlying emotion of the expresser. We integrate recent evidence in favor of a role for sensorimotor simulation in emotion recognition. We then connect this account to a domain-general understanding of how sensory information from multiple modalities is integrated to generate perceptual predictions in the brain. PMID- 26876365 TI - Bacteriophage can lyse antibiotic-resistant Pseudomonas aeruginosa isolated from canine diseases. AB - Pseudomonas aeruginosa is a pathogen frequently identified as the cause of diverse infections or chronic disease. This microbe has natural resistance to several kinds of antibiotics, because of the species' outer membrane, efflux pumps and growth as a biofilm. This bacterium can acquire increased resistance with specific point mutations. Bacteriophage (phage), however, can lyse these bacteria. Therefore, in the present study, we assessed the host range of phages isolates and their ability to lyse antibiotic-resistant P. aeruginosa. Present phages could lyse many strains of P. aeruginosa (28/39), including strains with high resistance to fluoroquinolones (4/6). In conclusion, application of phages for antibiotic-resistant bacteria is greatly effective. To avoid pervasive antibiotic-resistant bacteria, further development of phage usage for disease treatment is required. PMID- 26876364 TI - Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses. AB - We analyzed the AZFc region of the Y-chromosome for complete (b2/b4) and distinct partial deletions (gr/gr, b1/b3, b2/b3) in 822 infertile and 225 proven fertile men. We observed complete AZFc deletions in 0.97% and partial deletions in 6.20% of the cases. Among partial deletions, the frequency of gr/gr deletions was the highest (5.84%). The comparison of partial deletion data between cases and controls suggested a significant association of the gr/gr deletions with infertility (P = 0.0004); however, the other partial deletions did not correlate with infertility. In cohort analysis, men with gr/gr deletions had a relatively poor sperm count (54.20 +/- 57.45 million/ml) in comparison to those without deletions (72.49 +/- 60.06), though the difference was not statistically significant (p = 0.071). Meta-analysis also suggested that gr/gr deletions are significantly associated with male infertility risk (OR = 1.821, 95% CI = 1.39 2.37, p = 0.000). We also performed trial sequential analyses that strengthened the evidence for an overall significant association of gr/gr deletions with the risk of male infertility. Another meta-analysis suggested a significant association of the gr/gr deletions with low sperm count. In conclusion, the gr/gr deletions show a strong correlation with male infertility risk and low sperm count, particularly in the Caucasian populations. PMID- 26876366 TI - Evaluation of a Labelled Bacteriophage with 99mTc as a Potential Agent for Infection Diagnosis. AB - BACKGROUND AND OBJECTIVE: The design of target-specific molecular imaging probes to determine infection sites are mainly based on the biochemistry of the inflammatory response that may lead to an ideal agent for infection imaging. Infectious diseases timely and specifically diagnosed can be clinically challenging but essential for the patient's recovery. Laboratory tests can detect the responsible microorganism but cannot discriminate between sterile inflammatory disease and truly infectious disease. On the other hand, scintigraphic images, can pinpoint the infection in the body. METHODS: Bacteriophages (phages) are viruses that infect specific bacterial strains. Given the composition of the protein capsid, they could be used as radiopharmaceuticals to diagnose bacterial infection. In this case, PP7 phage was labelled and evaluated as a specific tracer for Pseudomonas aeruginosa infections. 99mTc-Phage synthesis used HYNIC as a bifunctional agent. Physicochemical evaluation included studies such as stability in time, ligand exchange, lipophilicity and bacterial binding assay. Three groups of animals namely; healthy, infected with Pseudomonas aeruginosa and induced sterile inflammation were used to conduct biological evaluation Results: The radiolabelling process required size exclusion purification of the 99mTc-Phage, which was obtained with a radiochemical purity higher than 90%, during 18 hours post labelling. The collective accumulation in the stomach, small intestine and large intestine and thyroid of 99mTc-Phage was negligible, indicating no in vivo reoxidation. The complex presented urinary elimination. Target/ non-target ratio (T/NT) was determined both for sterile inflammation and for infection. Values were 2.5 +/- 0.4 and 4.2 +/- 0.3 respectively. These values indicate significant differences between sterile inflammation and infection by Pseudomonas aeruginosa (p<0.05 unpaired two sided t test). CONCLUSION: Targeted biodistribution profile and good T/NT ratios, indicate that this complex presents enough specificity to discriminate between infection caused by Pseudomonas aeruginosa and sterile inflammation. PMID- 26876368 TI - Plain to point network reduced graphene oxide-activated carbon composites decorated with platinum nanoparticles for urine glucose detection. AB - In this study, a hydrothermal technique was applied to synthesize glucose-treated reduced graphene oxide-activated carbon (GRGO/AC) composites. Platinum nanoparticles (PtNP) were electrochemically deposited on the modified GRGO/AC surface, and chitosan-glucose oxidase (Chit-GOx) composites and nafion were integrated onto the modified surface of the working electrode to prepare a highly sensitive glucose sensor. The fabricated biosensor exhibited a good amperometric response to glucose in the detection range from 0.002 mM to 10 mM, with a sensitivity of 61.06 MUA/mMcm(2), a short response time (4 s) and a low detection limit of 2 MUM (signal to noise ratio is 3). The glucose sensor exhibited a negligible response to interference and good stability. In addition, the glucose levels in human urine were tested in order to conduct a practical assessment of the proposed sensor, and the results indicate that the sensor had superior urine glucose recognition. These results thus demonstrate that the noble nano structured electrode with a high surface area and electrocatalytic activity offers great promise for use in urine glucose sensing applications. PMID- 26876367 TI - Apolipoprotein E (APOE) epsilon4 and episodic memory decline in Alzheimer's disease: A review. AB - A growing body of research has examined the relationship between episodic memory decline, the cognitive hallmark of Alzheimer's disease (AD), and the presence of Apolipoprotein E epsilon4 (APOE epsilon4) allele, a major genetic risk factor for the disease. Our review attempts to summarize and critically evaluate this literature. We performed a systematic search for studies assessing episodic memory in AD patients who were genotyped for APOE epsilon4 and identified fourteen papers. Although most of these papers reported significant relationships between APOE epsilon4 and episodic memory decline in AD, some papers did not confirm this relationship. Our review links this controversy to the conflicting literature about the effects of APOE epsilon4 on general cognitive functioning in AD. We identify several shortcoming and limitations of the research on the relationship between APOE epsilon4 and episodic memory in AD, such as small sample sizes, non-representative populations, lack of comparison of early-onset vs. late-onset disease, and lack of comparison among different genotypes that include APOE epsilon4 (i.e., zero, one, or two epsilon4 alleles). Another major shortcoming of the reviewed literature was the lack of comprehensive evaluation of episodic memory decline, since episodic memory was solely evaluated with regard to encoding and retrieval, omitting evaluation of core episodic features that decline in AD, such as context recall (e.g., how, where, and when an episodic event has occurred) and subjective experience of remembering (e.g., reliving, emotion and feeling during episodic recollection). Future research taking these limitations into consideration could illuminate the nature of the relationship between APOE epsilon4 and episodic memory decline in AD. PMID- 26876369 TI - Critical Appraisal. Comparative Performance of Mineral Trioxide Aggregate Versus Calcium Hydroxide as a Direct Pulp Capping Agent. AB - Vital pulp therapy is the general concept involved in the "regenerative" restorative treatment of the reversibly injured dental pulp with the intention of maintaining its vitality in a restored, functioning tooth. While this procedure has been attempted with various materials and techniques over a period of several centuries, the advent of hard-setting calcium hydroxide materials in the late 1950s made the procedure of direct pulp capping a more routine and relatively predictable procedure. More recently, in the mid 1990s, a new type of water based, "hydraulic-type," calcium silicate-based cement, mineral trioxide aggregate (MTA), was introduced to dentistry as a possible alternative to the established standard of hard-setting calcium hydroxide. Over the last two decades, a slowly growing body of pre-clinical and human clinical studies evaluating and comparing these two materials has developed. Most recently, a number of well-designed, randomized controlled studies and resultant systematic reviews have been completed and published regarding the comparative efficacy of calcium hydroxide versus MTA for direct pulp capping. This Critical Appraisal considers and reviews some of the more recently published reports which provide a more definitive answer to this clinical research question. PMID- 26876370 TI - Keto-Enol Thermodynamics of Breslow Intermediates. AB - Breslow intermediates, first postulated in 1958, are pivotal intermediates in carbene-catalyzed umpolung. Attempts to isolate and characterize these fleeting amino enol species first met with success in 2012 when we found that saturated bis-Dipp/Mes imidazolidinylidenes readily form isolable, though reactive diamino enols with aldehydes and enals. In contrast, triazolylidenes, upon stoichiometric reaction with aldehydes, gave exclusively the keto tautomer, and no isolable enol. Herein, we present the synthesis of the "missing" keto tautomers of imidazolidinylidene-derived diamino enols, and computational thermodynamic data for 15 enol-ketone pairs derived from various carbenes/aldehydes. Electron withdrawing substituents on the aldehyde favor enol formation, the same holds for N,N'-Dipp [2,6-di(2-propyl)phenyl] and N,N'-Mes [2,4,6-trimethylphenyl] substitution on the carbene component. The latter effect rests on stabilization of the diamino enol tautomer by Dipp substitution, and could be attributed to dispersive interaction of the 2-propyl groups with the enol moiety. For three enol-ketone pairs, equilibration of the thermodynamically disfavored tautomer was attempted with acids and bases but could not be effected, indicating kinetic inhibition of proton transfer. PMID- 26876371 TI - Hydrothermal synthesis of Ag@MSiO2@Ag three core-shell nanoparticles and their sensitive and stable SERS properties. AB - An Ag@MSiO2@Ag three core-shell architecture was synthesized by a facial hydrothermal method. The features of the sample were characterized by SEM, TEM, and AFM images, EDS analyses and absorption spectra. This novel nanostructure exhibited excellent SERS properties due to the formation of hot spots around the inner and outer Ag NPs, which were identified by theoretical calculations. A detection limit of the analyte molecule was obtained as low as 10(-11) M by using this SERS nanostructure. Moreover, the homogeneity of SERS signals from the three core-shell nanostructure was checked by Raman mapping. Our studies show that the unique Ag@MSiO2@Ag three core-shell nanostructure has significant potential to realize a SERS substrate with both sensitivity and stability, which are important in SERS-based immunoassay. PMID- 26876372 TI - High-throughput 3D whole-brain quantitative histopathology in rodents. AB - Histology is the gold standard to unveil microscopic brain structures and pathological alterations in humans and animal models of disease. However, due to tedious manual interventions, quantification of histopathological markers is classically performed on a few tissue sections, thus restricting measurements to limited portions of the brain. Recently developed 3D microscopic imaging techniques have allowed in-depth study of neuroanatomy. However, quantitative methods are still lacking for whole-brain analysis of cellular and pathological markers. Here, we propose a ready-to-use, automated, and scalable method to thoroughly quantify histopathological markers in 3D in rodent whole brains. It relies on block-face photography, serial histology and 3D-HAPi (Three Dimensional Histology Analysis Pipeline), an open source image analysis software. We illustrate our method in studies involving mouse models of Alzheimer's disease and show that it can be broadly applied to characterize animal models of brain diseases, to evaluate therapeutic interventions, to anatomically correlate cellular and pathological markers throughout the entire brain and to validate in vivo imaging techniques. PMID- 26876373 TI - Zika virus and microcephaly: why is this situation a PHEIC? PMID- 26876375 TI - Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats. AB - Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-alpha, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-alpha, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters. PMID- 26876374 TI - Is there a role for the thinprep imaging system in reporting anal cytology? AB - BACKGROUND: The ThinPrep Imaging System (TIS) is an accurate time-saving method of reading cervical ThinPrep slides in screening programs. As anal and cervical cytology are morphologically similar, TIS can potentially be used for anal cytology. We assessed the performance of TIS on anal ThinPrep slides from homosexual men in a natural history study of human papillomavirus-related anal abnormalities. METHODS: Four hundred nineteen anal cytology slides were processed by TIS and classified by a cytologist as either No further review (slide archived) or Manual review (slide requiring full manual screen). The results were compared with the original manual screening report for all slides and specifically for those screening episodes accompanied by a high-grade squamous intraepithelial lesion (HSIL) on concurrent biopsy. RESULTS: One hundred seventy six of 419 (42.0%) slides were classified as No further review, with a trend of decreasing proportions as the degree of severity of the cytological abnormality increased. Thirteen (27.7%) slides with an original unsatisfactory report were classified as No further review. Eighty two (92.1%) of those with biopsy HSIL and cytological abnormality were classified for Manual review, including all 45 (100%) with cytological HSIL. CONCLUSION: The cervical algorithm of TIS performed best on anal samples when HSIL was present both cytologically and histologically. The 27.7% unsatisfactory slides classified as No further review may indicate need for use of different criteria from cervical cytology. Because of the high prevalence of abnormalities, and hence the large proportion of slides needing manual review, the cytologist time-saving would compare unfavorably with use of TIS in cervical screening. PMID- 26876376 TI - A biomimetic molecular switch at work: coupling photoisomerization dynamics to peptide structural rearrangement. AB - In spite of considerable interest in the design of molecular switches towards photo-controllable (bio)materials, few studies focused on the major influence of the surrounding environment on the switch photoreactivities. We present a combined experimental and computational study of a retinal-like molecular switch linked to a peptide, elucidating the effects on the photoreactivity and on the alpha-helix secondary structure. Temperature-dependent, femtosecond UV-vis transient absorption spectroscopy and high-level hybrid quantum mechanics/molecular mechanics methods were applied to describe the photoisomerization process and the subsequent peptide rearrangement. It was found that the conformational heterogeneity of the ground state peptide controls the excited state potential energy surface and the thermally activated population decay. Still, a reversible alpha-helix to alpha-hairpin conformational change is predicted, paving the way for a fine photocontrol of different secondary structure elements, hence (bio)molecular functions, using retinal-inspired molecular switches. PMID- 26876377 TI - An improved low-voltage ride-through performance of DFIG based wind plant using stator dynamic composite fault current limiter. AB - In this paper, an enhanced low-voltage ride-through (LVRT) performance of a grid connected doubly fed induction generator (DFIG) has been presented with the usage of stator dynamic composite fault current limiter (SDCFCL). This protection circuit comprises of a suitable series resistor-inductor combination and parallel bidirectional semiconductor switch. The SDCFCL facilitates double benefits such as reduction of rotor induced open circuit voltage due to increased value of stator total inductance and concurrent increase of rotor impedance. Both effects will limit rotor circuit over current and over voltage situation more secured way in comparison to the conventional scheme like the dynamic rotor current limiter (RCL) during any type of fault situation. The proposed concept is validated through the simulation study of the grid integrated 2.0MW DFIG. PMID- 26876378 TI - An integer order approximation method based on stability boundary locus for fractional order derivative/integrator operators. AB - This paper introduces an integer order approximation method for numerical implementation of fractional order derivative/integrator operators in control systems. The proposed method is based on fitting the stability boundary locus (SBL) of fractional order derivative/integrator operators and SBL of integer order transfer functions. SBL defines a boundary in the parametric design plane of controller, which separates stable and unstable regions of a feedback control system and SBL analysis is mainly employed to graphically indicate the choice of controller parameters which result in stable operation of the feedback systems. This study reveals that the SBL curves of fractional order operators can be matched with integer order models in a limited frequency range. SBL fitting method provides straightforward solutions to obtain an integer order model approximation of fractional order operators and systems according to matching points from SBL of fractional order systems in desired frequency ranges. Thus, the proposed method can effectively deal with stability preservation problems of approximate models. Illustrative examples are given to show performance of the proposed method and results are compared with the well-known approximation methods developed for fractional order systems. The integer-order approximate modeling of fractional order PID controllers is also illustrated for control applications. PMID- 26876379 TI - Linkage-length dependent structuring behaviour of bent-core molecules in helical nanostructures. AB - We studied the correlation between the molecular structure and the formation of helical nanofilaments (HNFs) of bent-core dimeric molecules with varying linkage lengths. To obtain precise structural data, a single domain of HNFs was prepared under physical confinement using porous 1D nanochannels, made up of anodic aluminium oxide films. Electron microscopy and grazing incidence X-ray diffraction were used to elucidate the linkage length-dependent formation of HNFs. PMID- 26876381 TI - Association between FAT1 mutation and overall survival in patients with human papillomavirus-negative head and neck squamous cell carcinoma. AB - BACKGROUND: The purpose of this study was to characterize the mutation profile of FAT atypical cadherin 1 (FAT1) and determine the prognostic significance of FAT1 mutation for overall survival in patients with human papillomavirus (HPV) negative head and neck squamous cell carcinoma (HNSCC). METHODS: Data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) data portals and used as discovery and validation sets. FAT1 mutational status was determined in 234 and 37 patients with HPV-negative HNSCC, respectively, and overall survival analysis was performed. For comparison, HPV positive patients were also analyzed for overall survival. RESULTS: Most of the identified nonsynonymous somatic FAT1 mutations were loss-of-function mutations. FAT1 mutation was significantly associated with better overall survival in HPV negative patients from both the TCGA cohort (p = .026) and the ICGC cohort (p = .047), but not in HPV-positive patients. CONCLUSION: FAT1 mutational status is a strong independent prognostic factor in patients with HPV-negative HNSCC. (c) 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E2021-E2029, 2016. PMID- 26876380 TI - Virus-mediated EpoR76E gene therapy preserves vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress. AB - BACKGROUND: Glaucoma is a complex neurodegeneration and a leading cause of blindness worldwide. Current therapeutic strategies, which are all directed towards lowering the intraocular pressure (IOP), do not stop progression of the disease. We have demonstrated that recombinant adeno-associated virus (rAAV) gene delivery of a form of erythropoietin with attenuated erythropoietic activity (EpoR76E) can preserve retinal ganglion cells, their axons, and vision without decreasing IOP. The goal of this study was to determine if modulation of neuroinflammation or oxidative stress played a role in the neuroprotective activity of EPO.R76E. METHODS: Five-month-old DBA/2J mice were treated with either rAAV.EpoR76E or a control vector and collected at 8 months of age. Neuroprotection was assessed by quantification of axon transport and visual evoked potentials. Microglia number and morphology and cytokine and chemokine levels were quantified. Message levels of oxidative stress-related proteins were assessed. RESULTS: Axon transport and visual evoked potentials were preserved in rAAV.EpoR76E-treated mice. The number of microglia was decreased in retinas from 8-month-old rAAV.EpoR76E-treated mice, but proliferation was unaffected. The blood-retina barrier was also unaffected by treatment. Levels of some pro inflammatory cytokines were decreased in retinas from rAAV.EpoR76E-treated mice including IL-1, IL-12, IL-13, IL-17, CCL4, and CCL5. TNFalpha messenger RNA (mRNA) was increased in retinas from 8-month-old mice compared to 3-month-old controls regardless of treatment. Expression of several antioxidant proteins was increased in retinas of rAAV.EpoR76E-treated 8-month-old mice. CONCLUSIONS: Treatment with rAAV.EpoR76E preserves vision in the DBA/2J model of glaucoma at least in part by decreasing infiltration of peripheral immune cells, modulating microglial reactivity, and decreasing oxidative stress. PMID- 26876382 TI - Pharmacological Manipulation of the Rostromedial Tegmental Nucleus Changes Voluntary and Operant Ethanol Self-Administration in Rats. AB - BACKGROUND: The aversive properties of ethanol (EtOH) that limit its intake are poorly understood. There is an increasing interest in the role of the rostromedial tegmental nucleus (RMTg), because it encodes aversion signals and inhibits motivated behaviors. It is also a major source of inhibitory GABAergic inputs to the midbrain dopamine neurons. Up to this time, the role of the RMTg in EtOH-drinking behaviors has not been well explored. METHODS: Male Long-Evans rats were trained either to drink EtOH under the intermittent 2-bottle-choice protocol or to self-administer EtOH in operant chambers under fixed-ratio-3 schedules. Changes in drinking behaviors induced by the bilateral infusion into the RMTg of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an agonist of AMPA-type glutamate receptors, or muscimol, an agonist of GABAA receptors, were measured. RESULTS: Consumption and preference for EtOH, numbers of active lever pressing, and head entrance to the EtOH port were all significantly decreased upon activation of the RMTg by the infusion of AMPA, but were increased upon inhibition of the RMTg by the infusion of muscimol. By contrast, intra-RMTg infusion of these agents did not change sucrose consumption. CONCLUSIONS: These data show for the first time that EtOH-drinking and EtOH-seeking behaviors of rats changed inversely with RMTg function, supporting the idea that the RMTg plays a crucial role in EtOH-drinking behaviors. PMID- 26876384 TI - Relapsing polychondritis: A clinical update. AB - Relapsing polychondritis (RP) is a rare connective tissue disease in which recurrent bouts of inflammation, involve the cartilage of the ears, nose, larynx, tracheobronchial tree and cardiovascular system. RP is generally observed in the fourth and fifth decades of life and occurs with equal frequency in both sexes. The cause of RP is still unknown. It is considered an immune-mediated disease, as there is an overlap between well documented RP with other rheumatic and autoimmune diseases. There is a significant association of RP with the antigen HLA-DR4. RP includes loss of basophilic staining of cartilage matrix perichondral accompanied by inflammation of the cartilage. Cells are present perivascular mononuclear and polymorphonuclear cells infiltrated. The chondrocytes become vacuolated and necrotic and are replaced by fibrous tissue. Common symptoms are often absent in the early stages of the disease in almost half the cases, resulting in delay in diagnosis. The development of chondrite allows the diagnosis of RP in patients initially evaluated for joint abnormalities, ocular, cutaneous, or audio-vestibular. Diagnostic criteria for RP are based on characteristic clinical manifestations. According to Damiani and Levine, the diagnosis can be considered final when one or more of the clinical features are present in conjunction with biopsy confirmation. The course of symptoms for patients with relapsing polychondritis is often unpredictable. Patients with mild signs of acute inflammation are usually treated with non-steroidal anti inflammatory drugs and small doses of prednisone. Patients with severe manifestations, such as airway compromise may require high doses of prednisone or even intravenous pulse methyl-prednisone. PMID- 26876383 TI - New insights into immune mechanisms underlying response to Rituximab in patients with membranous nephropathy: A prospective study and a review of the literature. AB - BACKGROUND: Idiopathic membranous nephropathy (MN) is a common immune-mediated glomerular disease and the main cause of nephrotic syndrome (NS) in Caucasian adults. Rituximab (RTX) has been reported to safely reduce proteinuria in patients with primary MN and severe NS. However, the effects of RTX treatment on T-cells including regulatory T-cells (Treg) in MN have not been fully determined. METHODS: Seventeen patients [mean age 67 (29-86) years, 6 women, 11 men] with biopsy-proven MN, and persistent proteinuria >3.5 g/24h were prospectively enrolled and received RTX, 375 mg/m(2) (iv) on days 1, 8, 15 and 22. Changes in circulating B and T cell homeostasis were examined in the peripheral blood by flow-cytometry studies; serum levels of IL-35 were measured using a high sensitivity ELISA kits (baseline, at month 3, 6, 9 and 12). RESULTS: Patients had been followed-up for a mean of 36.3 months (24-48). Proteinuria decreased from 5.6 (3.5-8) g/24h to 2.4 (0.06-13) g/24h at 6 months (p<0.05) and to 1.3 (0.06-8) at 12 months (p<0.01), respectively after therapy with RTX. Four patients received a 2nd course of RTX (one at 6 months because of persistent NS, and three at 12, 18, or 30 months for relapse). The three relapsing patients became proteinuria-free (<0.5 g/24h) in the following 6 months. Serum creatinine remained stable during the follow-up: median 1mg/dl (0.7-1.6) at 12 months and 1.1 (0.7-1.7) at 24 months as compared to 1 (0.5-2.4) at baseline. At 6 months after RTX, complete remission (CR) was observed in 7 patients, partial remission (PR) in 4, while 6 were non responders (NR) non responder (NR). At the end of the follow-up, 14 patients were in CR, 1 in PR, while 2 were NR. In the T-cell compartment, upon detection of B cell depletion, there was an increase in Treg up to 10-fold when comparing baseline and at month 12 (mean +/- SD 1.2 +/- 0.6%, and 5.8 +/- 0.7% p=0.02, respectively). When stratifying patients in responders (CR+PR) and NRs at month 12, we observed a significant increase in Treg cells from month 6 which persisted till 12 months only in the responder group (5.5 +/- 0.6% and 1.1 +/- 0.6%, p=0.04, respectively in responders and NRs). A statistically significant decrease in the levels of active T-lymphocytes (HLA DR+CD8+ cells) was observed, with a maximum reached at 12 months after treatment with RTX [6 +/- 1.1% baseline, 4.7 +/- 1.7% at 6 months (p=0.043) and 1.5 +/- 1.4% at 12 months (p=0.05)]. A marked increase in IL-35 levels [defined as delta >40% (serum values at 6 months minus baseline values)] was seen in 68% of the patients who achieved clinical response (CR or PR) at 12 month, but in none of the patients who failed to respond (p=0.034). CONCLUSION: Our findings and data from literature support the idea that RTX can be envisaged as a first-line therapy for patients at risk of progression because of persistent NS due to idiopathic MN. Insights into the putative T cell-related mechanisms of action have been discussed. PMID- 26876385 TI - Epidemiological, clinical and laboratory profiles of cutaneous polyarteritis nodosa patients: Report of 22 cases and literature review. AB - Cutaneous polyarteritis nodosa (CPAN) is a rare disease that affects small and middle caliber vessels of the deep dermis and subcutaneous tissue and its etiopathology remains yet to be understood. METHODS: Retrospective review of twenty two cases diagnosed as CPAN and confirmed by skin biopsy over the last 11 years was evaluated in our department. RESULTS: We found predominance in white woman, mean age of 39.4 years, showing no comorbidities in most of our sample. Mean follow-up time was 58 months. The most frequent cutaneous manifestations were ulcers, livedo racemosa, subcutaneous nodules, atrophie blanche lesions and purpuras; with lower limb involvement in all cases, however other areas were also involved. The main regional symptoms were pain and paresthesia, while systemic complaints were absent in the majority of cases. Mononeuritis multiplex was identified in a quarter of our sample. Most of the laboratory findings were non specific. There was evidence for previous contact with Mycobacterium tuberculosis in 46.1% of cases which were tested for purified protein derivative (PPD) test. In our patients the disease course was benign and without complications, and systemic polyarteritis nodosa did not develop in any patient. CONCLUSIONS: An extensive work-up including laboratory tests on autoimmunity and thrombophilic factors and investigation of infectious diseases, especially previous contact with tuberculosis agent, should be part of the CPAN investigation. PMID- 26876387 TI - Cannabinoids and autoimmune diseases: A systematic review. AB - Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders. PMID- 26876386 TI - New insight into the pathogenesis of minimal change nephrotic syndrome: Role of the persistence of respiratory tract virus in immune disorders. AB - The pathogenesis of minimal change nephrotic syndrome (MCNS) is a complex clinical problem which, unfortunately, has been in need of significant breakthroughs for decades. Improved understanding of the mechanisms is important to develop effective treatment strategies. To our knowledge, the pathogenesis of MCNS is multifactorial, involving both intrinsic and extrinsic factors, reasonable to be regarded as a "long chain" cascade reaction. Current studies implicating that the disease could probably be caused by immune disorders, however, have focused merely on the middle or terminal of this "long chain". It remains unclear what really triggers the immune disorders. It is noteworthy that the close association of respiratory tract infection with the occurrence, relapse and aggravation of nephrotic syndrome has been confirmed for over two decades. Derived from what we demonstrated in earlier studies, that the persistence of respiratory tract virus may contribute to the onset and development of MCNS, this review summarizes current evidence investigating the possible mechanisms of viral persistence, and discusses the role of viral persistence in the pathogenesis of MCNS. The key point is: whether the persistence of respiratory tract virus results in immune disorders. The available evidence under review also highlight the fact that the background of genetic susceptibility to the disease was found in many patients, which could be triggered by extrinsic factors, e.g. by the infection of respiratory tract virus. PMID- 26876389 TI - Crimean-Congo Haemorrhagic Fever: An Emerging Public Health Care Challenge in Pakistan. PMID- 26876388 TI - Plasma membrane insertion of epithelial sodium channels occurs with dual kinetics. AB - The epithelial sodium channel (ENaC) constitutes the rate-limiting step for Na(+) transport across electrically tight epithelia. Regulation of ENaC activity is critical for electrolyte and extracellular volume homeostasis, as well as for lung liquid clearance and colon Na(+) handling. ENaC activity is tightly controlled by a combination of mechanisms involving changes in open probability and plasma membrane abundance. The latter reflects a combination in channel biosynthesis and trafficking to and from the membrane. Studying ENaC trafficking with different techniques in a variety of expression systems has yielded inconsistent results, indicating either fast or slow rates of insertion and retrieval, which range from the order of minutes to several hours. Here, we use Xenopus oocytes as ENaC expression system to study channel insertion rate in the membrane using two different techniques under comparable conditions: (1) confocal microscopy coupled to fluorescence recovery after photobleaching (FRAP) measurements; and (2) fluorescent bungarotoxin (BTX) binding to ENaC subunits modified to include BTX binding sites (BBSs) in their extracellular domain, a technique that has not been previously used to study ENaC trafficking. Our confocal-FRAP data indicate a fast rate of ENaC incorporation to the membrane in a process conditioned by channel subunit composition. On the other hand, BTX binding experiments indicate much slower channel insertion rates, with matching slow ENaC retrieval rates. The data support a model that includes fast recycling of endocytosed ENaC with parallel incorporation of newly synthesized channels at a slower rate. PMID- 26876390 TI - In Vitro Comparative Study of Two Different Bleaching Agents on Micro-hardness Dental Enamel. AB - OBJECTIVE: To evaluate the effect of home-use bleaching agent containing 16% Carbamide Peroxide (CP) and in-office bleaching agent containing 38% Hydrogen Peroxide (HP) on enamel micro-hardness. STUDY DESIGN: An in vitroexperimental study. PLACE AND DURATION OF STUDY: Department of Operative Dentistry and Science of Dental Materials at Dr. Ishrat-ul-Ebad Khan Institute of Oral Health Sciences, Dow University of Health Sciences and Material Engineering Department of NED University of Engineering and Technology, Karachi, from July to December 2014. METHODOLOGY: Atotal of 90 enamel slabs from 45 sound human 3rd molar were randomly divided into 3 groups. Each group contained 30 specimens (n=30). Group 1 was kept in artificial saliva at 37 degrees C in incubator during the whole experiment. However, Groups 2 and 3 were treated with power whitening gel and tooth whitening pen respectively. After bleaching session, specimens were thoroughly rinsed with deionized water again for 10 seconds and then stored in artificial saliva at 37 degrees C in incubator. Artificial saliva was changed after every 2 days. The Vickers hardness tester (Wolpert 402 MVD, Germany) was adjusted to a load of 0.1 kg (100 gm) and dwell time of 5 seconds. Three Vickers were performed on each specimen using a hardness tester according to the ISO 6507 3:1998 specification. Micro-hardness measurements were performed before and after bleaching at day 1, 7 and 14. RESULTS: In the control group, the baseline micro hardness was 181.1 ±9.3 which was reduced after the storage on day 1, 7 and 14 (p = 0.104). In Group 2, baseline micro-hardness was 180.4 ±10.1 which was reduced to 179.79 ±10.0 units after day 1. Whereas, on day 7 and 14, the values of micro-hardness were 179.8 ±10 and 179.7 ±10.29, respectively (p=0.091). Furthermore, the baseline micro-hardness in Group 3 was 174.0 ±22.9 units which was reduced to 173 ±23 on day 1, 170 ±30 on day 7 and 173 ±23 on day 14 (p = 0.256). The statistically insignificant difference was found among micro-hardness values of different bleaching agents (p = 0.118). CONCLUSION: Bleaching with 38% Hydrogen Peroxide (HP) and 16% Carbamide Peroxide (CP) resulted in insignificant effect on surface micro-hardness of enamel. PMID- 26876391 TI - Decreased Serum 25-Hydroxycalciferol Levels in Pre-diabetic Adults. AB - OBJECTIVE: To determine the serum 25-hydroxycalciferol levels [25(OH)D] in adults with pre-diabetes and normoglycaemia to examine a possible association of vitamin D deficiency with pre-diabetes. STUDY DESIGN: Case control study. PLACE AND DURATION OF STUDY: Armed Forces Institute of Pathology, Rawalpindi, from November 2012 to July 2013. METHODOLOGY: Atotal of 272 adults including 136 pre-diabetics and 136 normoglycaemics of either gender aged 20 years and above were consecutively inducted. Patients with diabetes mellitus, pregnancy, rickets and osteomalacia, ischemic heart disease, chronic kidney disease and chronic liver disease were excluded. Fasting Plasma Glucose (FPG) was estimated with hexokinase method on Modular p800 Roche chemistry analyzer while serum 25(OH)D was measured on Diasorin Liaison immunoassay analyzer using the chemiluminescent technique. Mean 25(OH)D levels in pre-diabetic and normoglycaemic groups were compared using Mann-Whitney U test. Spearman's correlation coefficient 'rs' was determined between serum 25(OH)D and FPG. Odds ratio for vitamin D deficiency was also calculated. RESULTS: Mean serum 25(OH)D level was low in pre-diabetics (23.2 nmol/L) as compared to normoglycaemics (29 nmol/L; p=0.001). Serum 25(OH)D level had inverse correlation with FPG (rs= -0.448, p=0.000). There was also significant association of vitamin D deficiency with pre-diabetes compared with normoglycaemia (OR: 2.21, p= 0.016; 95% CI: 1.15-4.27). CONCLUSION: Vitamin D deficiency with pre-diabetes suggested that vitamin D may have an important role in pathogenesis of pre-diabetes. PMID- 26876392 TI - New-Style Laparoscope and Endoscope Cooperative Gallbladder-Preserving Surgery for Polyps. AB - OBJECTIVE: To evaluate the feasibility and safety of a new style of Laparoscope and Endoscope Cooperative gallbladderpreserving Surgery (LECS), an improved method of minimally invasive gallbladder-preserving polypectomy. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of General Surgery, The Second Affiliated Hospital of Soochow University, China, from January 2009 to July 2013. METHODOLOGY: Clinical data of patients subjected to LECS and Laparoscopic Cholecystectomy (LC) was analysed. The inclusion criteria were normal size clear gallbladder bile with total volume (FV) of the gallbladder = 15 - 25 ml, the Residual Volume (RV) = 5 ml, and the Emptying Figure (EF) > 75%, with polyps diagnosed definitively by B-type ultrasonic imaging or CTdesirous of preserving gallbladder. Exclusion criteria were a history of midsection surgery, serious diseases of any organ, hepatic injury, or coagulation disturbance. Mean hospital stay and complications were also noted. Independent sample t-test, the frequency comparison used chi-square test (N > 5), and Fisher's exact test (N < 5) were used for statistical test. RESULTS: The mean hospital stay after LECS was 3.50 +/-0.31 days, and 3.50 +/-0.31 days for the LC group. The mean age in LC and LECS group was 50 +/-25.4 and 44 +/-12.1 years, respectively. Complications after operation in the LECS were indigestion and diarrhea; LC group had indigestion (9.33%), diarrhea (10.67%), and gastroesophageal reflux (6.6.7%). In the 3 months follow-up after discharging from the hospital, no patient had recurrence of any gallbladder disease; at 1 year follow-up, 1 patient (1.28%) developed cholesterol crystals; at 3-year follow-up, 3 cases (3.84%) were found to have recurring polyps (2~4 pieces), and 2 (2.56%) patients developed cholesterol crystals. CONCLUSION: Minimally invasive gallbladder-preserving polypectomy which used a CHIAO cholecystoscopy compared with a laparoscope is safe, feasible, and can effectively reduce the vestiges and recrudescence of polyps in gallbladderpreserving surgery. PMID- 26876393 TI - Pancreas Divisum. AB - OBJECTIVE: To evaluate the complications, technical success, diagnostic evaluation and various endoscopic management options in patients with pancreas divisum. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Endoscopy Suite, Surgical Unit 4, Civil Hospital, Karachi, from January 2007 to December 2013. METHODOLOGY: All Endoscopic Retrograde Cholangio-pancreatography (ERCPs) procedure performed in patients with pancreas divisum were analyzed. Success was defined as having authentic diagnostic information or a successful endoscopic therapy for the condition. RESULTS: During the study period, 3600 patients underwent 4500 ERCPprocedures. Pancreas divisum was found in 17 patients (0.47%); 7 ERCPs (41.2%) were performed for diagnostic and 10 (58.8%) for therapeutic purposes. Sixteen (94.1%) had complete PD and one (5.9%) had incomplete PD. Male and Female ratio was 1:1.83 with a mean age of 26.3 years and median symptom duration of 11 months. Atotal of 23 procedures were performed in 17 patients; 2 had ERCP done thrice, 2 underwent the procedure twice, while the rest had single procedure done. Six (35.3%) patients had chronic pancreatitis, 7 (41.2%) had acute recurrent pancreatitis and 4 (23.5%) had acute pancreatitis. Endoscopic minor papillotomy was performed. There was no procedure-related mortality. ERCPaffected management in 88.2% (15/17 procedures). CONCLUSION: ERCPis a safe and feasible procedure for pancreas divisum patients. PMID- 26876394 TI - Surgical Site Infection in Diabetic and Non-Diabetic Patients Undergoing Laparoscopic Cholecystectomy. AB - OBJECTIVE: To compare the frequency of surgical site infections in patients with type II diabetes undergoing laparoscopic cholecystectomy as compared with non diabetic patients. STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Surgical Unit 2, Services Hospital, Lahore, from May to October 2012. METHODOLOGY: Patients were divided into two groups of 60 each, undergoing laparoscopic cholecystectomy. Group A comprised non-diabetic patients and group B comprised type II diabetic patients. Patients were followed postoperatively upto one month for the development of SSIs. Proportion of patients with surgical site infections or otherwise was compared between the groups using chi-square test with significance of p < 0.05. RESULTS: In group A, 35 patients were above the age of 40 years. In group B, 38 patients were above the age of 40 years. Four patients in group Adeveloped a surgical site infection. Seven patients in group B developed SSIs (p = 0.07). CONCLUSION: Presence of diabetes mellitus did not significantly affect the onset of surgical site infection in patients undergoing laparoscopic cholecystectomy. PMID- 26876395 TI - Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma. AB - OBJECTIVE: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. METHODOLOGY: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. RESULTS: Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55%) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29%) of all cases and was reported in 87 (36.4%) of NHLand 6 (7.5%) of HL. The most common extra nodal site was the gastrointestinal tract. CONCLUSION: Hodgkin lymphoma comprises 25% and non Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma. PMID- 26876396 TI - Immunoinformatic Analysis of Crimean Congo Hemorrhagic Fever Virus Glycoproteins and Epitope Prediction for Synthetic Peptide Vaccine. AB - OBJECTIVE: To determine the Crimean Congo Hemorrhagic Fever (CCHF) virus M segement glycoprotein's immunoinformatic parameters, and identify Human Leukocyte Antigen (HLA) class I binders as candidates for synthetic peptide vaccines. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Combined Military Hospital, Khuzdar Cantt, in May 2015. METHODOLOGY: Data acquisition, antigenicity prediction, secondary and tertiary structure prediction, residue analysis were done using immunoinformatics tools. HLAclass I binders in glycoprotein's sequence were identified at nanomer length using NetMHC 3.4 and mapped onto tertiary structure. Docking was done for strongest binder against its corresponding allele with CABS-dock. RESULTS: HLAA*0101, 0201, 0301, 2402, 2601 and B*0702, 0801, 2705, 3901, 4001, 5801, 1501 were analyzed against two glycoprotein components of the virus. Atotal of 35 nanomers from GP1, and 3 from GP2 were identified. HLAB*0702 bound maximum number of peptides (6), while HLAB*4001 showed strongest binding affinity. CONCLUSION: HLAspecific glycoproteins epitope prediction can help identify synthetic peptide vaccine candidates. PMID- 26876397 TI - Frequency of Candida albicans in Patients with Funguria. AB - OBJECTIVE: To determine the frequency of Candida albicansin patients with funguria. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Department of Microbiology, Sindh Institute of Urology and Transplantation, from July to December 2012. METHODOLOGY: Patients' urine samples with fungus/Candida were included. Candida albicans was identified by the production of tubular structures (germ tubes) on microscopy as per standard procedure followed by inoculation on Chrom agar (Oxoid) and Corn Meal-Tween 80 agar (Oxoid). The identification of other non-albicans Candidaspecies was also done both microscopically and macroscopically as per standard procedure. RESULTS: Out of the 289 isolates, 204 (70.6%) were male patients and 85 (29.4%) were female patients, with 165 (57.1%) from the out-patients and 124 (42.9%) from the in-patients. Five species of Candidawere found to be prevalent including 87 (30.1%) Candida albicans, 176 (60.9%) Candida tropicalis, 14 (4.8%) Candida parapsilosis, 8 (2.8%) Candida glabrata and 4 (1.4%) Candida lusitaniae. Majority of patients with funguria were aged above 50 years (60.2%). CONCLUSION: In the present study, 30.1% patients with funguria had Candida albicans. The most frequently isolated species was Candida tropicalis(60.9%), followed by other non albicansCandida. This study has shown the emergence of non-albicans Candidaas a major cause of candiduria. PMID- 26876398 TI - Postoperative Functional Outcome of Intradural Extramedullary Spinal Tumors Through Posterior Approach. AB - OBJECTIVE: To determine functional outcome of intradural extramedullary spinal tumors in patients undergoing excision through the posterior approach alone. STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Neurosurgery Department, JPMC, Karachi, from March 2011 to February 2014. METHODOLOGY: Patients with intradural extramedullary spinal tumors (IDEM), confirmed on MRI, were admitted through Outpatient Department. Those with bleeding disorders, diabetes mellitus, previously operated and with no histopathological evidence of tumor on biopsy, were excluded. Clinical signs, symptoms and location of the tumor were noted. These patients then underwent laminectomy and excision of tumor through the posterior approach, regardless of the location or type of tumor. Transpedicular screw was placed where the tumor was so large, as to cause posterior instability. The functional outcome was evaluated by assessment of Medical Research Council (MRC) Scale for Muscle Strength preoperatively and at 6 months follow-up postoperatively. Good outcome was labelled when there was improvement from previous grade before surgery to higher grade, as assessed by muscle strength on follow-up at 6 months after surgery. RESULTS: The mean age of the 38 patients was 42.6 +/-10 years. Majority were females (68.42%). Meningioma was the commonest tumor (63.15%). The commonest location was thoracic spine (73.68%). Backache was present in all (100%) patients, motor weakness in 30 (78.92%) patients, sensory disturbance in 5 (13.5%) patients, sphincter disturbance in 7 (18.42%) patients, and shortness of breath in 1 (2.63%) patient. Preoperatively, there were 10 patients (26.31%) in grade 3, 9 (23.68%) patients in grade 0, 8 (21.05%) in grade 1, 7 (18.42%) patients in grade 2. After 6 postoperative months, there were 23 (60.52%) patients in grade 5, 5 (13.15%) patients in grade 3, 5 (13.15%) patients in grade 2 and 2 (5.26%) patients in grade 1. Postoperative complications were CSF leak, respiratory distress, wound infection and incontinence. CONCLUSION: Functional outcome of intradural extramedullary spinal tumors was found to be good. PMID- 26876399 TI - Efficacy of 2.5% and 1.25% Povidone-Iodine Solution for Prophylaxis of Ophthalmia Neonatorum. AB - OBJECTIVE: To determine the efficacy of 2.5% and 1.25% Povidone-Iodine solution for Ophthalmia neonatorum prophylaxis. STUDY DESIGN: Interventional study. PLACE AND DURATION OF STUDY: Eye Department, Combined Military Hospital, Sargodha, from May to November 2014. METHODOLOGY: Atotal of 200 eyes of 100 newborn babies were enrolled and divided into two groups of 100 right eyes and 100 left eyes. Aconjunctival swab for bacterial culture was taken within 30 minutes after delivery. Asingle drop of 2.5% Povidone-Iodine was then placed in the right eye while in the left eye a single drop of 1.25% Povidone-Iodine was placed. Thirty minutes after placing Povidone-Iodine, a conjunctival swab was again taken. Abacterial suspension was prepared from each swab in determining bacterial counts. The bacterial suspension was inoculated on yeast extract agar and the number of colony forming units were counted. At each culture, the number of colony forming units before and after instillation of 2.5% Povidone-Iodine and 1.25% Povidone-Iodine were compared. Wilcoxon's signed rank test was used for statistical analysis. RESULTS: The 2.5% Povidone-Iodine solution caused a statistically significant decrease in the number of colony forming units (p=0.001). Similarly, the 1.25% Povidone-Iodine solution also reduced the number of colony forming units to a statistically significant level (p=0.001). CONCLUSION: The 1.25% concentration of Povidone-Iodine is as effective as the 2.5% concentration of Povidone-Iodine in reducing the number of colony forming units in healthy conjunctivae of newborns. PMID- 26876400 TI - The Impact of Body Mass Index on Oral Hygiene Practices of Adolescents in Bhopal City, India. AB - OBJECTIVE: To assess the impact of Body Mass Index (BMI) on oral hygiene practices of adolescents in Bhopal City, India. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Arts College, Bhopal, from February to March 2014. METHODOLOGY: Aconvenience sample of 17 - 23 years college-going adolescents from Arts College, Bhopal city was selected for the study. Self-reported questionnaire for adolescents to assess BMI and oral hygiene attitude, knowledge and practices was used. Descriptive statistics and chi-square test were applied. RESULTS: Out of the total study population, 53.54% (n=166) were males and 46.45% (n=144) were females. Two hundred and six (66.45%) were of optimal weight, 27.74% (n=86) were underweight and only 4.52% (n=14) were overweight. There was a significant association between BMI and oral hygiene practice of toothbrushing (p < 0.001) and mouth rinsing (p=0.001) among both male and female subjects. CONCLUSION: Hence, BMI is significantly associated with the oral hygiene practices of adolescent population. There is growing interest in the relationship between BMI and oral health because both are significant public health concerns. These public health problems are related to common lifestyle factors such as unhealthy eating habits and smoking among children. These maladapted habits track into later life as predictors of increased BMI and oral health problems. Hence, it is required that the dentists are aware of the influence of body mass Index and lifestyle on oral health practices among children and adolescents. PMID- 26876401 TI - Dual Diagnosis and Suicide Probability in Poly-Drug Users. AB - OBJECTIVE: To determine the frequency of suicidal thoughts and suicidal probability among poly-substance abusers in Saudi population, and to examine the relation between dual diagnosis and suicidal thoughts. STUDY DESIGN: Case control study. PLACE AND DURATION OF STUDY: Al-Baha Psychiatric Hospital, Saudi Arabia, from May 2011 to June 2012. METHODOLOGY: Participants were 239 subjects, aged 18 45 years. We reviewed 122 individuals who fulfilled the DSM-IV-TR criteria of substance abuse for two or more substances, and their data were compared with that collected from 117 control persons. RESULTS: Suicidal cases were highly present among poly-substance abusers 64.75%. Amphetamine and cannabis were the most abused substances, (87.7% and 70.49%, respectively). Astatistically significant association with suicidality was found with longer duration of substance abuse (p < 0.001), using alcohol (p=0.001), amphetamine (p=0.007), volatile substances (p=0.034), presence of comorbid psychiatric disorders (dual diagnosis) as substance induced mood disorder (p=0.001), schizo-affective disorder (p=0.017), major depressive disorders (p=0.001), antisocial (p=0.016) and borderline (p=0.005) personality disorder. Suicidal cases showed significant higher scores (p < 0.001) of suicide probability scale and higher scores in Beck depressive inventory (p < 0.001). CONCLUSION: Abusing certain substances for long duration, in addition to comorbid psychiatric disorders especially with disturbed mood element, may trigger suicidal thoughts in poly-substance abusers. Depression and suicide probability is common consequences of substance abuse. PMID- 26876402 TI - Pathological Investigation of Childhood Foreskin: Are Lichen Sclerosus and Phimosis Common? AB - OBJECTIVE: To evaluate histopathological results of foreskin removed during circumcision in the pediatric age group and the relationship between these and the degree of phimosis. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Urology, Samsun Training and Research Hospital, Samsun, Turkey, from June to December 2014. METHODOLOGY: Male children undergoing planned circumcision were examined for the presence and degree of phimosis which was recorded before the operation. After circumcision, the preputial skin was dermatopathologically investigated. Pathological investigation carefully evaluated findings such as acute inflammation, chronic inflammation, increased pigmentation and atrophy in addition to findings of Lichen Sclerosus (LS) in all specimens. The pathological findings obtained were classified by degree of phimosis and evaluated. RESULTS: The average age of the 140 children was 6.58 +/ 2.35 years. While 61 (43.6%) children did not have phimosis, 79 (56.4%) patients had different degrees of phimosis. Classic LS was not identified in any patient. In a total of 14 (10%) children, early period findings of LS were discovered. The frequency of LS with phimosis was 12.6%, without phimosis was 6.5% (p=0.39). The incidence of histopathologically normal skin in non-phimosis and phimosis groups was 37.7% and 22.7%, respectively. In total, 41 (29.3%) of the 140 cases had totally normal foreskin. CONCLUSION: Important dermatoses such as LS may be observed in foreskin with or without phimosis. The presence of phimosis may be an aggravating factor in the incidence of these dermatoses. PMID- 26876403 TI - Repair and Regenerative Therapies of the Annulus Fibrosus of the Intervertebral Disc. AB - Degeneration of the intervertebral disc is implicated as the main cause of low back pain. Current treatment strategies for degenerative disc disease, such as conservative treatments and surgeries, only relieve the symptoms of low back pain without treating the causes of underlying degeneration. Surgical treatments cannot reverse the degeneration of the intervertebral disc degeneration, and may even accelerate the degeneration. The development of tissue engineering and regenerative therapeutic strategies have brought new hope for repair and regeneration of the degenerated intervertebral disc. These strategies have been developed mainly targeting to the repair and regeneration of the nucleus pulposus of the degenerated but intervertebral disc. Although many studies that focused on the nucleus pulposus repair have achieved successes in laboratory settings but disc repair without giving much regard to annulus fibrosus could not recover the normal mechanical environment, which might make the disc degenerative change continuously exacerbate. Lately, the strategy to simultaneously repair the damaged annulus fibrosus and nucleus pulposus has attracted more attention, which could be considered to slow the disc degenerative rate and obtain better repair effect. An extensive literature search up to March 2015 for annulus fibrosus repair and regeneration in vitro or in vivo studies and clinical trials with the key words of "annulus fibrosus, repair, regeneration, tissue engineering, intervertebral disc and scaffold" were performed through PubMed, China National Knowledge Infrastructure and China Biology Medicine. The goal of this paper was to review the current research progress of annulus fibrosus repair and regeneration, and also suggest directions for future research. PMID- 26876404 TI - Thinking Out of the Box: Alternative Career Choices for Young Doctors in Pakistan. AB - The number of young medical graduates in Pakistan is increasing every year. Most of whom wish to specialize in a particular clinical field. Considering the competition faced for specialty training selection and later on for job placement, it is suggested that these young graduates should explore some alternative careers as well. Opportunities can be availed and decision made based on graduates' personal interest, preference to work in Pakistan or abroad, and availability of suitable employment in local and international hospitals among other factors. Careers in the basic medical sciences, medical education, medical research, medical writing and bioethics can be considered, too. There are very few trained professionals in these fields in Pakistan and once trained, these young doctors will hopefully find rewarding employment. PMID- 26876405 TI - Distal Esophageal Duplication Cyst with Gastro-Esophageal Reflux Disease: A Rare Association and a Management Challenge. AB - Esophageal duplication cysts are rare congenital abnormalities of the foregut and may be associated with other conditions. Association of esophageal duplication with Gastro-Esophageal Reflux Disease (GERD) has not been reported in children. We are reporting a case of a 16 months baby who had antenatal diagnosis of diaphragmatic hernia. Postnatal CTchest, however, suggested a distal esophageal duplication cyst and a contrast esophagogram showed grade-IV GER. A thoracoscopy in another hospital excluded esophageal duplication at that time. Later, he presented with hematemesis in our department and was re-evaluated. Repeat CTconfirmed a persistent 2.5 x 1.3 cm cyst in distal esophagus. Upper GI endoscopy suggested grade-II esophagitis with a wide patent gastro-esophageal junction. The child was treated with left thoracotomy, excision of the duplication cyst and thoracic fundoplication. He had an uneventful post-operative recovery and is doing well at 6 months follow-up. PMID- 26876406 TI - An Unusual Case of Crimean Congo Hemorrhagic Fever: Prolonged Bleeding with Successful Recovery. AB - Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wild animals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases are being reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is most likely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinical presentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts. PMID- 26876408 TI - Reach the Leech: An Unusual Cause of Hematuria. AB - Leeches are found in fresh water as well as moist marshy tropical areas. Orifical Hirudiniasis is the presence of leech in natural human orifices. Leech have been reported in nose, oropharynx, vagina, rectum and bladder but leech per urethra is very rare. We report a case of leech in urethra causing hematuria and bleeding disorder in the form of epistaxis and impaired clotting profile after use of stream water for ablution. The case was diagnosed after a prolonged diagnostic dilemma. Asingle alive leech was recovered from the urethra after ten days with the help of forceps. The hematuria and epistaxis gradually improved over next 48 hours and the patient became asymptomatic. Natives of leech infested areas should be advised to avoid swimming in fresh water and desist from drinking and using stream water without inspection for leeches. PMID- 26876407 TI - Fibrodysplasia Ossificans Progressiva. AB - Fibrodysplasia Ossificans Progressiva (FOP) is a rare autosomal dominant disorder characterized by postnatal progressive heterotopic ossification of connective tissue and congenital malformation of big toes. We report a 3-year male toddler with clinical and radiological features of FOP. He was born with bilateral hallux valgus and at the age of 3 years presented with hard swellings over back, scapular region and forehead that were initially inflammatory and then became bony hard. There is also tilting of neck towards the left due to calcification in neck region. The radiographs showed heterotopic ossification in thoracic region, neck, spine and region of hip joint. PMID- 26876409 TI - Medical Students' Perception of OSCE at the Department of Internal Medicine, College of Medicine, King Khalid University, Abha, KSA. AB - The aim of this study was to explore the students' acceptance of Objective Structured Clinical Examination (OSCE) as a method of assessment of clinical competence in internal medicine. This cross sectional study was conducted from June to August 2013, at King Khalid University, Abha, KSA, through a self administered questionnaire which was completed by fourth year medical students, immediately after the OSCE. Student feedback confirmed their acceptance of OSCE. This was encouraging to the department to consider implementing OSCE for graduating students. PMID- 26876410 TI - Use of Massive Online Open Courses as a Potential Resource to Provide Continuing Medical Education in Pakistan. AB - The Pakistan Medical and Dental Council (PM&DC) has made Continuing Medical Education (CME) mandatory for doctors, from 2015 onwards. Aminimum of 15 credit hours of CME per year for general practitioners and 30 credit hours for specialist doctors have been made mandatory for renewal of the PMDC registration. While doctors can attend conferences to earn this CME credit, the opportunities are minimum and limited to major cities across Pakistan. Webbased CME is an attractive alternative to attending conferences. It can make up for 25% of the yearly PMDC requirement. So far, only two web-based CME providers have been launched in Pakistan, which is a shortage. Could Massive Online Open Courses (MOOCs) be used to fill this shortage? The MOOCs are online courses that are easily accessible to all learners irrespective of geographical boundary and resources, and can be used as a tool to provide CME to physicians. The problem as to how credit from PM&DC can be obtained, will need to be explored further. PMID- 26876411 TI - Energetics of the Heart. PMID- 26876412 TI - An Analysis of 3-Port Laparoscopic Cholecystectomy: How often 4th Port is Required? PMID- 26876413 TI - Tailoring Precision of the Size-15 Surgical Knife at Laparoscopic Porting. PMID- 26876415 TI - ERRATUM. PMID- 26876414 TI - Expanding the HINARI Initiative for Healthcare Research in Pakistan. PMID- 26876416 TI - Short Communication: Do Cytomegalovirus Antibody Levels Associate with Age Related Syndromes in HIV Patients Stable on Antiretroviral Therapy? AB - HIV(+) persons stable on antiretroviral therapy (ART) face early onset of age related diseases. This may arise from a high burden of cytomegalovirus (CMV). To address the role of CMV, we investigated univariate and multivariate associations between markers of systemic and endothelial inflammation, vascular damage, insulin resistance (IR), neurocognitive decline, and antibodies reactive with CMV. In this study, HIV(+) participants (n = 91) aged >45 years with <50 copies HIV RNA/ml plasma after >2 years on ART were assessed for cardiovascular risk (the D:A:D algorithm), type II diabetes (the HOMA-IR index), and neurocognitive performance. Blood samples were assayed for lipids, T cells, insulin, glucose, C reactive protein, CX3CL1, sTNF-R1, total immunoglobulin G (IgG), and antibodies reactive with CMV lysate, glycoprotein B, or immediate-early-1. Levels of antibodies detected with the three antigens were tightly correlated. Levels of CMV lysate antibody were higher in patients than in age-matched healthy controls and reflected their nadir CD4 T-cell count (p = .001), total IgG (p = .02), and age (p = .08). Levels of CMV lysate antibody correlated with D:A:D score (p = .04), neurocognitive performance (p = .045), and fasting insulin (p = .02). In multivariable analyses, some associations reflected the effect of age, but CMV lysate antibody and CD8 T-cell counts were significant predictors of the HOMA-IR index (R(2) = 0.09, p = .01) independent of age. We conclude that associations between levels of CMV antibodies, cardiovascular risk, and neurocognitive health in HIV(+) patients stable on ART are moderated by age-associated increases in response to CMV, while CMV antibodies may be independently linked with IR. PMID- 26876417 TI - Context-dependent seed dispersal by a scatter-hoarding corvid. AB - Corvids (crows, jays, magpies and nutcrackers) are important dispersers of large seeded plants. Studies on captive or supplemented birds suggest that they flexibly adjust their scatter-hoarding behaviour to the context of social dynamics and relative seed availability. Because many corvid-dispersed trees show high annual variation in seed production, context-dependent foraging can have strong effects on natural corvid scatter-hoarding behaviour. We investigated how seed availability and social dynamics affected scatter-hoarding in the island scrub jays (Aphelocoma insularis). We quantified rates of scatter-hoarding behaviour and territorial defence of 26 colour-marked birds over a three-year period with variable acorn crops. We tested whether caching parameters were correlated with variation in annual seed production of oaks as predicted by the predator dispersal hypothesis, which states that caching rates and distances should vary with seed abundance in ways that benefit tree fitness. We also tested whether antagonistic interactions with conspecifics would affect scatter-hoarding adversely, as found in experimental studies. Caching behaviour varied with acorn availability. Caching distances correlated positively with annual acorn crop size, increasing by as much as 40% between years. Caching rates declined over time in years with small acorn crops, but increased when crops were large. Acorn foraging and caching rates were also negatively correlated with rates of territorial aggression. Overall foraging rates, however, were not associated with aggression, suggesting that reduced dispersal rates were not simply due to time constraints. Our field results support laboratory findings that caching rates and distances by scatter-hoarding corvids are context-dependent. Furthermore, our results are consistent with predictions of the predator dispersal hypothesis and suggest that large seed crops and social interactions among scatter-hoarders affect dispersal benefits for oaks and other masting tree species. PMID- 26876419 TI - Natural history of coexistent mitral regurgitation after aortic valve replacement. AB - OBJECTIVES: The long-term evolution of coexistent mitral regurgitation (MR) after aortic valve replacement (AVR) for aortic stenosis remains poorly defined. Prior studies have demonstrated that acute improvement in MR after AVR is modest, and more aggressive approaches have been advocated. This study examines the evolution of MR after AVR and identifies prognostic indicators for MR improvement. METHODS: We retrospectively evaluated demographic and echocardiographic data of 423 patients who underwent primary isolated AVR for aortic stenosis with coexistent mild (n = 314) or moderate (n = 109) MR at our institution, from 2004 to 2013. For each patient, preoperative and postoperative MR was extracted from 903 echocardiograms and graded on a 0 to 4+ scale. Hierarchic linear models were used to estimate postoperative residual MR over a 5-year follow-up period. Patients were then stratified by improvement in MR, and preoperative risk factors and survival were compared between groups. Cox proportional hazards regression was used to assess the association between survival and preoperative and postoperative MR. RESULTS: The overall acute reduction in MR was -0.23 degrees per patient. Patients with moderate MR had a -0.53 degree reduction in MR, whereas patients with mild MR had only a -0.13 degree reduction in MR (P < .001). Residual MR, however, worsened over time and regressed back to baseline, particularly in patients with preoperative moderate MR. At last follow-up, 70 (17%) patients returned to 2+ or worse MR. Residual MR at last echocardiographic follow-up was not affected by left ventricular ejection fraction, severity of preoperative aortic valve gradient (AVG), magnitude of reduction of AVG, or other comorbidities. Degree of preoperative MR did not affect midterm survival. Patients whose MR improved after AVR demonstrated a trend toward improved survival (75% vs 65% 5-year survival; P = .06), compared with those without MR whose survival remained unchanged or worsened. CONCLUSIONS: Coexistent MR modestly improves after AVR, but eventually regresses back to baseline or worsens over time in many patients. Preoperative AVG, reduction of AVG, heart failure, or atrial fibrillation was not predictive of residual MR. Moderate preoperative MR did not adversely affect 5-year survival. Patients with improvement in MR, however, demonstrated a trend toward improved survival at 5 years. More aggressive approaches for coexistent moderate MR should be considered in patients who need AVR for aortic stenosis. PMID- 26876420 TI - Defining operative mortality: Impact on outcome reporting. AB - OBJECTIVE: Death is an important outcome of procedural interventions. The death rate, or mortality rate, is subject to variability by definition. The Society of Thoracic Surgeons Adult Cardiac Surgery Database definition of "operative" mortality originally included all in-hospital deaths and deaths occurring within 30 days of the procedure. In recent versions of the Society of Thoracic Surgeons Adult Cardiac Surgery Database, "in-hospital" has been modified to include "patients transferred to other acute care facilities," and "deaths within 30 days unless clearly unrelated to the procedure" has been changed to "deaths within 30 days regardless of cause." This study addresses the impact of these redefinitions on outcome reporting. METHODS: The California Office of Statewide Health Planning and Development hospitalized patient discharge database was queried for the year 2009, the most recent year that data files could be linked to the vital statistics death files to include all-cause mortality. Isolated coronary artery bypass grafting, isolated valve, coronary artery bypass grafting valve, and percutaneous coronary intervention procedures were identified by International Classification of Diseases, Ninth Edition, Clinical Modification procedure codes. Percutaneous coronary intervention procedures were further divided into acute coronary syndrome (percutaneous coronary intervention acute coronary syndrome) and all other percutaneous coronary intervention (percutaneous coronary intervention no acute coronary syndrome). Deaths were counted by 5 methods depending on the time and place of occurrence: (1) in-hospital or during the index hospitalization; (2) in-hospital + connected hospitalization, defined as a transfer to another acute care facility on the same day or within 24 hours of discharge; (3) in-hospital + 30 day, death during index hospitalization or within 30 days after the procedure; (4) in-hospital + connected + 30 day readmission, death during index hospitalization, transfer to acute care facility, or deaths during readmission within 30 days; and (5) in-hospital + connected + 30 day. To study the impact of these operative mortality definitions, we examined 5 different methods to track mortality and performed 2 separate analyses. The first analysis did not exclude any patients, and the second analysis excluded any patient who could not be accurately tracked after hospital discharge. RESULTS: In the first analysis with no patients excluded, a total of 17% (117/697) of surgical deaths and 31% (409/1324) of percutaneous coronary intervention deaths were counted after the original hospitalization. The highest percentage of posthospital deaths occurred after elective percutaneous coronary intervention: 45% (135/301). In surgical patients, the highest percentage of posthospital deaths occurred in coronary artery bypass grafting procedures: 20% (57/284). In the second analysis, with untrackable patients excluded, hospital deaths included 12% (161/1324) for percutaneous coronary intervention compared with 4% (30/697) for surgical procedures. CONCLUSIONS: A significant percentage of procedural deaths occur after transfer or discharge from the index hospital. This is especially evident in the percutaneous coronary intervention group. These findings illustrate the importance of the definition of "operative" mortality and the need to ensure accuracy in the reporting of data to voluntary clinical registries, such as the Society of Thoracic Surgeons Adult Cardiac Surgery Database and National Cardiovascular Data Registry. PMID- 26876421 TI - Discussion. PMID- 26876422 TI - Discussion. PMID- 26876423 TI - The Metabolic Syndrome: A Risk Factor for the Frailty Syndrome? PMID- 26876424 TI - Magnetoelectric effect in organic molecular solids. AB - The Magnetoelectric (ME) effect in solids is a prominent cross correlation phenomenon, in which the electric field (E) controls the magnetization (M) and the magnetic field (H) controls the electric polarization (P). A rich variety of ME effects and their potential in practical applications have been investigated so far within the transition-metal compounds. Here, we report a possible way to realize the ME effect in organic molecular solids, in which two molecules build a dimer unit aligned on a lattice site. The linear ME effect is predicted in a long range ordered state of spins and electric dipoles, as well as in a disordered state. One key of the ME effect is a hidden ferroic order of the spin-charge composite object. We provide a new guiding principle of the ME effect in materials without transition-metal elements, which may lead to flexible and lightweight multifunctional materials. PMID- 26876425 TI - A Randomised Trial of a Positive Intervention to Promote Well-Being in Cardiac Patients. AB - BACKGROUND: Negative emotions are linked to the onset and development of coronary heart diseases (CHD), whereas positive emotions are associated with better health and lower mortality rates among patients with these diseases. The objective of this randomised trial was to improve cardiac patients' emotional states using a Programme to Improve Well-being (PIW) based exclusively on positive interventions (those that promote intentional behaviours and thoughts to improve well-being). METHODS: Cardiac patients (n = 108) were randomly assigned to two parallel groups. In the control group, they participated in only a Cardiac Rehabilitation Programme (CRP group), whereas the intervention group also participated in the PIW (CRP+PIW group). Physical functional capacity, depressive symptoms, hostility, and negative and positive affect were assessed at T1 (baseline) and T2 (8 weeks later). RESULTS: At T2, after controlling for functional capacity, the CRP+PIW group reported a significantly less negative affect than the CRP group. Moreover, the CRP group did not change from T1 to T2, whereas the CRP+PIW group reported more positive emotions and fewer negative emotions and hostility at T2 than at T1. CONCLUSIONS: Positive interventions effectively improve the emotional state of cardiac patients. We suggest that specific modules should be included in the CRP to improve well-being. PMID- 26876426 TI - Quantitative agreement between [(15)O]H2O PET and model free QUASAR MRI-derived cerebral blood flow and arterial blood volume. AB - The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [(15)O]H2O positron emission tomography (PET) and model-free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r(2): 0.28-0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBVA was moderately correlated (r(2): 0.28-0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [(15)O]H2O-derived values (P < 0.001). Group-wise voxel statistics identified minor areas with significant contrast differences between [(15)O]H2O PET and QUASAR MRI, indicating similar qualitative CBVA and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [(15)O]H2O PET provide similar CBF and CBVA information, but with systematic quantitative discrepancies. PMID- 26876428 TI - Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution II: Solvent Coordinate-Dependent Reaction Path. AB - The protonation of methylamine base CH3NH2 by carbonic acid H2CO3 within a hydrogen (H)-bonded complex in aqueous solution was studied via Car-Parrinello dynamics in the preceding paper (Daschakraborty, S.; Kiefer, P. M.; Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. J. Phys. Chem. B 2016, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented, with specific emphasis on the water solvent's role. The overall reaction is barrierless and very rapid, on an ~100 fs time scale, with the proton transfer (PT) event itself being very sudden (<10 fs). This transfer is preceded by the acid-base H-bond's compression, while the water solvent changes little until the actual PT occurrence; this results from the very strong driving force for the reaction, as indicated by the very favorable acid protonated base DeltapKa difference. Further solvent rearrangement follows immediately the sudden PT's production of an incipient contact ion pair, stabilizing it by establishment of equilibrium solvation. The solvent water's short time scale ~120 fs response to the incipient ion pair formation is primarily associated with librational modes and H-bond compression of water molecules around the carboxylate anion and the protonated base. This is consistent with this stabilization involving significant increase in H-bonding of hydration shell waters to the negatively charged carboxylate group oxygens' (especially the former H2CO3 donor oxygen) and the nitrogen of the positively charged protonated base's NH3(+). PMID- 26876427 TI - Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase. AB - AIMS: To examine whether co-administration of intestinal alkaline phosphatase (IAP) with antibiotics early in life may have a preventive role against metabolic syndrome (MetS) in mice. METHODS: A total of 50 mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin (AZT) +/- IAP, or with no AZT +/- IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered a regular chow diet for 5 weeks and subsequently a high-fat diet for 5 weeks. Body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine the differences in microbiome composition. RESULTS: Exposure to AZT early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with AZT completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP probably occur as a result of changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides). CONCLUSIONS: Co-administration of IAP with AZT early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans. PMID- 26876430 TI - The ATPase Inhibitory Factor 1 (IF1): A master regulator of energy metabolism and of cell survival. AB - In this contribution we summarize most of the findings reported for the molecular and cellular biology of the physiological inhibitor of the mitochondrial H(+)-ATP synthase, the engine of oxidative phosphorylation (OXPHOS) and gate of cell death. We first describe the structure and major mechanisms and molecules that regulate the activity of the ATP synthase placing the ATPase Inhibitory Factor 1 (IF1) as a major determinant in the regulation of the activity of the ATP synthase and hence of OXPHOS. Next, we summarize the post-transcriptional mechanisms that regulate the expression of IF1 and emphasize, in addition to the regulation afforded by the protonation state of histidine residues, that the activity of IF1 as an inhibitor of the ATP synthase is also regulated by phosphorylation of a serine residue. Phosphorylation of S39 in IF1 by the action of a mitochondrial cAMP-dependent protein kinase A hampers its interaction with the ATP synthase, i.e., only dephosphorylated IF1 interacts with the enzyme. Upon IF1 interaction with the ATP synthase both the synthetic and hydrolytic activities of the engine of OXPHOS are inhibited. These findings are further placed into the physiological context to stress the emerging roles played by IF1 in metabolic reprogramming in cancer, in hypoxia and in cellular differentiation. We review also the implication of IF1 in other cellular situations that involve the malfunctioning of mitochondria. Special emphasis is given to the role of IF1 as driver of the generation of a reactive oxygen species signal that, emanating from mitochondria, is able to reprogram the nucleus of the cell to confer by various signaling pathways a cell-death resistant phenotype against oxidative stress. Overall, our intention is to highlight the urgent need of further investigations in the molecular and cellular biology of IF1 and of its target, the ATP synthase, to unveil new therapeutic strategies in human pathology. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. PMID- 26876431 TI - Review article: recent advances in pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in inflammatory bowel disease. AB - BACKGROUND: Azathioprine and mercaptopurine have a pivotal role in the treatment of inflammatory bowel disease (IBD). However, because of their complex metabolism and potential toxicities, optimal use of biomarkers to predict adverse effects and therapeutic response is paramount. AIM: To provide a comprehensive review focused on pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in IBD. METHODS: A literature search up to July 2015 was performed in PubMed using a combination of relevant MeSH terms. RESULTS: Pre treatment thiopurine S-methyltransferase typing plus measurement of 6-tioguanine nucleotides and 6-methylmercaptopurine ribonucleotides levels during treatment have emerged with key roles in facilitating safe and effective thiopurine therapy. Optimal use of these tools has been shown to reduce the risk of adverse effects by 3-7%, and to improve efficacy by 15-30%. For the introduction of aldehyde oxidase (AOX) into clinical practice, the association between AOX activity and AZA dose requirements should be positively confirmed. Inosine triphosphatase assessment associated with adverse effects also shows promise. Nucleoside diphosphate-linked moiety X-type motif 15 variants have been shown to predict myelotoxicity on thiopurines in East Asian patients. However, the impact of assessments of xanthine oxidase, glutathione S-transferase, hypoxanthine guanine phosphoribosyltransferase and inosine monophosphate dehydrogenase appears too low to favour incorporation into clinical practice. CONCLUSIONS: Measurement of thiopurine-related enzymes and metabolites reduces the risk of adverse effects and improves efficacy, and should be considered part of standard management. However, this approach will not predict or avoid all adverse effects, and careful clinical and laboratory monitoring of patients receiving thiopurines remains essential. PMID- 26876429 TI - The medical complications associated with purging. AB - OBJECTIVE: Purging behaviors, including self-induced vomiting, laxative abuse, and diuretic abuse, are present across many of the eating disorders. Here we review the major medical complications of these behaviors. METHOD: Although we identified over 100 scholarly articles describing medical complications associated with purging, most papers involved case studies or small, uncontrolled samples. Given the limited evidence base, we conducted a qualitative (rather than systematic) review to identify medical complications that have been attributed to purging behaviors. RESULTS: Medical conditions affecting the teeth, esophagus, gastrointestinal system, kidneys, skin, cardiovascular system, and musculoskeletal system were identified, with self-induced vomiting causing the most medical complications. DISCUSSION: Purging behavior can be associated with severe medical complications across all body systems. Mental health professionals should refer patients with purging behaviors to medical providers for screening and treatment as needed. The medical work-up for individuals with eating disorders should include a comprehensive metabolic panel, complete blood count, and a full body exam including the teeth to prevent severe complications. Medical providers should screen patients for purging behaviors and associated medical complications, even in the absence of an eating disorder diagnosis, to increase the detection of eating disorders. Recognizing the link between purging and medical complications can aid in identifying potential eating disorders, particularly those that often elude detection such as purging disorder. PMID- 26876432 TI - A case of Lemierre's Syndrome with a brief literature review. AB - The last fifteen years have witnessed a remarkable increase in the reported cases of Lemierre's Syndrome (LS), which was once called the forgotten disease. LS manifests as oropharyngitis and a blood stream infection with Fusobacterium necrophorum and internal jugular vein thrombosis. LS is a challenge for clinicians, as it is often difficult to diagnose and is associated with significant morbidity. In recognition of the importance of raising the awareness about rare diseases, herein, we describe a case of LS in a 21-year-old male that was treated successfully after two weeks of hospitalization; we have also included a brief literature review. PMID- 26876433 TI - Molecular detection and antimicrobial resistance of Klebsiella pneumoniae from house flies (Musca domestica) in kitchens, farms, hospitals and slaughterhouses. AB - Identifying disease vectors and pathogens is one of the key steps in controlling vector-borne diseases. This study investigated the possible role of house flies (Musca domestica) as vectors in the transmission of Klebsiella pneumoniae in Chaharmahal VA Bakhtiari and Isfahan provinces of Iran. House flies were captured from household kitchens, cattle farms, chicken farms, animal hospitals, human hospitals and slaughterhouses. Isolation of K. pneumoniae from external surfaces and guts of the flies was performed using MacConkey agar (MA) and thioglycollate broth (TGB). Identification of the isolates was performed with phenotypic techniques and polymerase chain reaction (PCR). A total of 600 house flies were sampled during the study period from different locations in four different seasons. Overall, 11.3% of the captured house flies were positive for K. pneumoniae. In Chaharmahal VA Bakhtiari province, the prevalence was 12.7%, while in Isfahan province, 10.0% of the sampled house flies were infected with K. pneumoniae. Season-wise, the highest prevalence of infections among the house flies was in summer. The organisms were highly resistant to ampicillin, amoxicillin, cefotaxime and piperacillin. A lowest level of resistance was observed for imipenem/cilastatin. The findings of this study demonstrated that house flies are potential vectors of antibiotic-resistant K. pneumoniae in Isfahan and Chaharmahal provinces, Iran. Control efforts for infections caused by this particular bacterium should take M. domestica into account. PMID- 26876434 TI - Upregulation of inflammasome activity and increased gut permeability are associated with obesity in children and adolescents. AB - BACKGROUND: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity. METHODS: The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro inflammatory cytokines (interleukin (IL)-1beta and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects. RESULTS: Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-gamma, IL-12beta, IL-1beta, CCL2, CCL5, IL-6 and TNFalpha) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1beta and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months. CONCLUSIONS: In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity. PMID- 26876435 TI - Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. AB - Early-life antibiotic exposure can disrupt the founding intestinal microbial community and lead to obesity later in life. Recent studies show that omega-3 fatty acids can reduce body weight gain and chronic inflammation through modulation of the gut microbiota. We hypothesize that increased tissue levels of omega-3 fatty acids may prevent antibiotic-induced alteration of gut microbiota and obesity later in life. Here, we utilize the fat-1 transgenic mouse model, which can endogenously produce omega-3 fatty acids and thereby eliminates confounding factors of diet, to show that elevated tissue levels of omega-3 fatty acids significantly reduce body weight gain and the severity of insulin resistance, fatty liver and dyslipidemia resulting from early-life exposure to azithromycin. These effects were associated with a reversal of antibiotic-induced dysbiosis of gut microbiota in fat-1 mice. These results demonstrate the beneficial effects of omega-3 fatty acids on antibiotic-induced gut dysbiosis and obesity, and suggest the potential utility of omega-3 supplementation as a safe and effective means for the prevention of obesity in children who are exposed to antibiotics. PMID- 26876436 TI - Preventive effect of sildenafil on right ventricular function in rats with monocrotaline-induced pulmonary arterial hypertension. AB - The present study aimed to evaluate the preventive effect of sildenafil treatment on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Fifty-four 12-week-old male Sprague-Dawley rats were injected with MCT or saline solution (MCT-injected rats: n=36; saline: n=18). Serial echocardiography and right ventricular systolic pressure (RVSP) measurements via a cardiac catheter were performed at 2, 4 and 6 weeks after the injection. After injection of MCT, rats received oral sildenafil (MCT/sildenafil group: n=18) or no treatment (MCT group: n=18) until undergoing echocardiography and cardiac catheterization. RVSP in the MCT/sildenafil group was lower than that in the MCT group at 4 (P<0.001) and 6 weeks (P<0.001). The septal curvature was improved in the MCT/sildenafil group compared with the MCT group. This finding showed that sildenafil prevented flattening of the interventricular septum because of right ventricular pressure overload. The ratio of peak trans-tricuspid early diastolic wave velocity to active filling with atrial systolic velocity showed that sildenafil improved diastolic function. Tricuspid annular plane systolic excursion and tricuspid annular systolic velocity in the MCT/sildenafil group did not show preserved myocardial contraction after administration of sildenafil. Administration of sildenafil leads to a reduction in RVSP and improvement in cardiac function in rats with PH induced by MCT. The vasodilatory action of sildenafil improves right ventricular diastolic function, but the intrinsic, positive, inotropic effect of sildenafil is minimal. PMID- 26876437 TI - Combining isoflurane anesthesia with midazolam and butorphanol in rats. AB - Representative inhalant anesthetic agent, isoflurane is commonly used during surgery in rats. However, isoflurane mediates relatively strong respiratory depression. In human and veterinary medicine, sedatives and analgesics are co administered to complement the anesthetic action of inhalant anesthesia. The present study aimed to establish the novel balanced anesthesia that combines midazolam and butorphanol with isoflurane (MBI) in rats. Male Sprague Dawley rats were divided into 2 groups, and administered either isoflurane monoanesthesia or isoflurane with midazolam (2.5 mg/kg, ip) and butorphanol (2.0 mg/kg, ip). The minimum alveolar concentration (MAC) in each group was evaluated. Induction and recovery times were measured in each group. Adverse reactions during induction were also recorded. In each group, vital signs were assessed for 1 h under 1.5*MAC of isoflurane. Instability of vital signs was assessed under each anesthesia by calculating coefficient of variance. Compared with isoflurane monoanesthesia, MBI anesthesia caused 32% MAC reduction (isoflurane monoanesthesia: 1.30 +/- 0.09%, MBI 0.87 +/- 0.08%, P<0.05). MB premedication mediated smooth sedating action with low incidence of adverse reactions such as urination and defecation. Isoflurane monoanesthsesia remarkably decreased respiratory rate and saturation O2 (SPO2). In contrast, MBI anesthesia resulted in a relatively stable respiratory rate without decreases in SPO2 during the anesthetic period. In summary, MB premedication is effective for attenuating respiratory depression induced by isoflurane, and achieving smooth induction. This anesthetic protocol serves as a novel option for appropriate anesthesia in rats. PMID- 26876438 TI - Innocuity of a commercial live attenuated vaccine for epizootic hemorrhagic disease virus serotype 2 in late-term pregnant cows. AB - Epizootic hemorrhagic disease (EHD) is an arthropod-borne infectious viral disease sustained by the epizootic hemorrhagic disease virus (EHDV). The only commercially available and currently used vaccines are manufactured for EHDV-2 in Japan, either live or inactivated vaccines. In this study we tested the innocuity for fetuses of the live attenuated EHDV-2 vaccine in five late-term pregnant cows. Whole blood and serum samples were collected from dams and screened for the presence of EHDV-2 RNA, infectious virus and antibodies. After calving, whole blood and serum samples collected from calves, before and after colostrum intake, were also tested for antibodies and for virus detection. In dams, neither fever nor clinical signs were observed. All of them seroconverted and a strong humoral response was detected throughout the sampling period. All blood samples tested negative for EHDV-2 except for one sample collected from a dam 11 days post vaccination which tested positive at virus isolation at the third cell passage following two rounds of blind passages. Although they had free access to colostrum, calves tested serologically negative for EHDV-2 during the entire course of the experiment. Overall, the tested live attenuated vaccine can be safely administered to late-term pregnant cows as it was not demonstrated to cross the placental barrier. The safety of the live-attenuated vaccine is further confirmed by the emergence of Ibaraki virus in 2013 in Japan which is apparently not related to the spread of the vaccine strain currently used in Japan. PMID- 26876439 TI - Global epidemiology of capsular group W meningococcal disease (1970-2015): Multifocal emergence and persistence of hypervirulent sequence type (ST)-11 clonal complex. AB - Following an outbreak in Mecca Saudi Arabia in 2000, meningococcal strains expressing capsular group W (W) emerged as a major cause of invasive meningococcal disease (IMD) worldwide. The Saudi Arabian outbreak strain (Hajj clone) belonging to the ST-11 clonal complex (cc11) is similar to W cc11 causing occasional sporadic disease before 2000. Since 2000, W cc11 has caused large meningococcal disease epidemics in the African meningitis belt and endemic disease in South America, Europe and China. Traditional molecular epidemiologic typing suggested that a majority of current W cc11 burden represented global spread of the Hajj clone. However, recent whole genome sequencing (WGS) analyses revealed significant genetic heterogeneity among global W cc11 strains. While continued spread of the Hajj clone occurs in the Middle East, the meningitis belt and South Africa have co-circulation of the Hajj clone and other unrelated W cc11 strains. Notably, South America, the UK, and France share a genetically distinct W cc11 strain. Other W lineages persist in low numbers in Europe, North America and the meningitis belt. In summary, WGS is helping to unravel the complex genomic epidemiology of group W meningococcal strains. Wider application of WGS and strengthening of global IMD surveillance is necessary to monitor the continued evolution of group W lineages. PMID- 26876440 TI - Risk factors for measles in children aged 8 months-14 years in China after nationwide measles campaign: A multi-site case-control study, 2012-2013. AB - INTRODUCTION: Endemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated more than 100 million children in 2010. In 2011, almost half of the 9943 measles cases in China occurred in children eligible for measles vaccination. We conducted a case-control study during 2012-2013 to identify risk factors for measles infection in children aged 8 months-14 years. METHODS: Children with laboratory-confirmed measles were age- and neighborhood-matched with three controls. We interviewed parents of case and control infants on potential risk factors for measles. We calculated adjusted matched odds ratios and 95% confidence intervals of risk factors. We calculated attributable fractions for risk factors that could be interpreted as causal and vaccine efficacy (VE) for the measles containing vaccine (MCV) used in the Chinese immunization program. RESULTS: In all, 969 case-patients and 2845 controls were enrolled. In multivariable analysis, lack of measles vaccination both overall (mOR 22.7 [16.6, 31.1] and when stratified by region (east region, mOR 74.2 [27.3, 202]; central/western regions mOR 17.4 [12.5, 24.3]), hospital exposure (mOR 63.0, 95% CI [32.8, 121]), and migration among counties (overall mOR 3.0 [2.3, 3.9]) were significant risk factors. The calculated VE was 91.9-96.1% for a single dose of MCV and 96.6-99.5% for 2 doses. CONCLUSIONS: Lack of vaccination was the leading risk factor for measles infection, especially in children born since the 2010 supplementary immunization activity. Reducing missed vaccination opportunities, improving immunization access for migrant children, and strengthening school/kindergarten vaccine checks are needed to strengthen the routine immunization program and maintain progress toward measles elimination in China. PMID- 26876441 TI - Heat shock protein complex vaccines induce antibodies against Neisseria meningitidis via a MyD88-independent mechanism. AB - BACKGROUND: Neisseria meningitidis are common colonizers of the human nasopharynx. In some circumstances, N. meningitidis becomes an opportunistic pathogen that invades tissues and causes meningitis. While a vaccine against a number of serogroups has been in effective use for many years, a vaccine against N. meningitidis group B has not yet been universally adopted. Bacterial heat shock protein complex (HSPC) vaccines comprise bacterial HSPs, purified with their chaperoned protein cargo. HSPC vaccines use the intrinsic adjuvant activity of their HSP, thought to act via Toll-like receptors (TLR), to induce an immune response against their cargo antigens. This study evaluated HSPC vaccines from N. meningitidis and the closely related commensal N. lactamica. RESULTS: The protein composition of N. lactamica and N. meningitidis HSPCs were similar. Using human HEK293 cells we found that both HSPCs can induce an innate immune response via activation of TLR2. However, stimulation of TLR2 or TLR4 deficient murine splenocytes revealed that HSPCs can activate an innate immune response via multiple receptors. Vaccination of wildtype mice with the Neisseria HSPC induced a strong antibody response and a Th1-restricted T helper response. However, vaccination of mice deficient in the major TLR adaptor protein, MyD88, revealed that while the Th1 response to Neisseria HSPC requires MyD88, these vaccines unexpectedly induced an antigen-specific antibody response via a MyD88 independent mechanism. CONCLUSIONS: N. lactamica and N. meningitidis HSPC vaccines both have potential utility for immunising against neisserial meningitis without the requirement for an exogenous adjuvant. The mode of action of these vaccines is highly complex, with HSPCs inducing immune responses via both MyD88 dependent and -independent mechanisms. In particular, these HSPC vaccines induced an antibody response without detectable T cell help. PMID- 26876442 TI - Context-dependent use of muscle spindles for human position sense. PMID- 26876443 TI - Acid-sensing ion channel 1a induces AMPA receptor plasticity: a link between acidotoxicity and excitotoxicity in hippocampal CA1 neurons. PMID- 26876444 TI - Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats. AB - Glial cell line-derived neurotrophic factor (GDNF) is a potential therapeutic protein on a variety of central nervous system diseases including ischemic stroke. However, GDNF is a large molecule that cannot cross the blood-brain barrier (BBB), which is still intact in the early hours after stroke when neural rescue is possible. PEP-1 protein transduction domain can deliver protein cargo across the cell membrane and the BBB. In the present study, we generated a novel fusion protein PEP-1-GDNF and examined whether PEP-1-GDNF is protective in focal cerebral ischemia. PEP-1-GDNF (200 MUg/kg) or PBS was intravenously applied over 5 min immediately after reperfusion of 90 min transient middle cerebral artery occlusion (MCAO). After 28 days, rats were deeply anesthetized and decapitated. Behavioral tests were performed during this period. The results showed that PEP-1 GDNF significantly reduced the infarct volume and improved behavioral function. Further, PEP-1-GDNF promoted the cell proliferation and differentiation in the dentate gyrus of the hippocampus and attenuated ischemia-induced learning and memory damage. PMID- 26876446 TI - The role of the cerebellum in motor imagery. AB - OBJECTIVE: Although it is well documented that the cerebellum plays a role in motor imagery (MI), its exact role in MI is still obscure. Since motor imagery and execution of movement share common pathways, and the cerebellum has an inhibitory effect on the motor cortex, we speculated that the cerebellum also has an inhibitory role on MI. METHODS: To test this hypothesis, 12 healthy individuals aged 27-47 years (mean age 33.3 years) were enrolled in the study. Subjects were asked to imagine two different tasks, one complex (MI-c) and one simple (MI-s) motor task. The intensity of anodal cerebellar transcranial direct current stimulation (ctDCS) was set at 2 mA for 20 min. Sham ctDCS consisted of 30s current stimulation. RESULTS: MI-s resulted in significantly increased log MEP amplitude during MI, compared with control MEP amplitude,(p=0.000). The increase in log MEP amplitude during MI disappeared after anodal ctDCS. Before sham ctDCS, both MI-s and MI-c resulted in log MEP amplitude increases (p=0.000). This facilitator effect of both MI-c and MI-s on log MEP amplitude was also persistent after sham ctDCS (p=0.000). CONCLUSIONS: The study demonstrates for the first time that the cerebellum has an inhibitory effect on MI. SIGNIFICANCE: Combining ctDCS with MI significantly modulates corticomotor excitability. PMID- 26876445 TI - Protective effects of a Chotosan Fraction and its active components on beta amyloid-induced neurotoxicity. AB - Chotosan (CTS) is a traditional Kampo prescription used to treat chronic headache and hypertension. Recent clinical studies demonstrated that CTS has ameliorative effects on dementia. This study aims to identify the anti-Alzheimer components in CTS. beta-amyloid (Abeta) is considered to play a central role in the pathophysiology of Alzheimer's disease. CTS-E, a fraction of CTS, showed significant protective effects on Abeta-induced neurotoxicity. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used for the qualitative analysis of it. Among the identified constituents, neuroprotective effects against Abeta(25-35)-induced neurotoxicity of 10 major compounds were tested by MTT assay. Their inhibitory action on Abeta(1-42) self induced aggregation was measured by Thioflavin T-binding assay. The results showed that caffeic acid, chlorogenic acid, 1,5-dicaffeoylquinic acid, 3,5 dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid had significant neuroprotective effects on Abeta(25-35)-induced neurotoxicity. Besides these phenolic acids, nobiletin and hesperidin could also inhibit Abeta(1-42) self induced aggregation. In conclusion, the neuroprotective fraction, CTS-E, could protect PC12 cells from Abeta-induced neurotoxicity. Anti-oxidative effects may at least partly mediate the neuroprotective effects of it. Phenolic acids from Chrysanthemi Flos and flavonoids from Citri Reticulatae Pericarpium might be the effective constituents in CTS-E. PMID- 26876447 TI - Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats. AB - Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5 U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression. PMID- 26876448 TI - Serum apolipoprotein E is associated with long-term risk of Alzheimer's disease: The Rotterdam Study. AB - BACKGROUND: Serum levels of apolipoprotein E (apoE) have been suggested as potential biomarker for dementia, but the long-term association between apoE and risk of dementia is uncertain. METHODS: Between 1990 and 1993, we measured serum apoE by immunoassay in 1042 non-demented individuals (mean +/- SD age 68.4 +/- 7.3 years; 59.3% women) from the population-based Rotterdam Study. Follow-up for dementia was complete until 2014. We used Cox models to determine the risk of dementia and Alzheimer's disease in relation to apoE, adjusting for age, sex, educational level, cardiovascular risk factors, and additionally APOE genotype. RESULTS: Serum apoE was associated to APOE genotype (p-trend=1.0E-51, r(2)=0.21). In men, apoE tended to be lower with age, whereas in women the opposite was observed (p-trend=0.07 and 0.08, respectively). During a median follow-up of 15.7 years (IQR 9.7-21.7), 220 participants developed dementia, of whom 180 had Alzheimer's disease. Lower serum apoE was associated with an increased risk of dementia (HR, 95%CI, per SD decrease: 1.25, 1.05-1.48) and in particular Alzheimer's disease (1.51, 1.23-1.86), which remained statistically significant for Alzheimer's disease after additionally adjusting for APOE genotype (1.28, 1.01-1.62). When stratifying analyses in 5-year time frames, risk estimates were similar throughout the study period. Serum apoE tended to marginally improve 20 year prediction of Alzheimer's disease (IDI 0.008, 95%CI -0.001-0.026, p=0.086), but not all dementia. CONCLUSION: Serum apoE is associated with long-term risk of Alzheimer's disease in the general population, independent of APOE genotype. Additional predictive value of serum apoE was limited. PMID- 26876449 TI - The influence of dental occlusion on the body balance in unstable platform increases after high intensity exercise. AB - Existing evidence suggests that body balance ability is associated with dental occlusion. The purpose of this study was to determine whether: (i) there are differences in balance between opposed dental occlusion (intercuspal position, ICP; cotton rolls, CR) for two extreme levels of stability and (ii) the influence of dental occlusion on the balance control gets stronger under fatigue conditions. To this aim, various measures for assessing postural control in ten physically active subjects were obtained prior to and following a maximal lower limbs exercise consisting in six sets of fifteen seconds stretch-shortening cycle jumping. Balance control at stable and unstable condition was evaluated on an unstable platform Balance System SD for both dental occlusion conditions at random order. Metabolic and psychological measurements ensured the high intensity of the exercise. At unstable level, balance control was significantly improved in the CR condition, for both rest (p=0.03) and fatigue (p<0.001). Whereas at stable level, the influence of dental occlusion only reached significance in fatigue condition (p=0.04). It could be concluded that the sensory information linked to the dental occlusion for the balance control comes strongly into effect when more difficult conditions for the balance control are present (i.e., unstable conditions, fatigue). PMID- 26876450 TI - Sall1 transiently marks undifferentiated heart precursors and regulates their fate. AB - Cardiac progenitor cells (CPCs) are a crucial source of cells in cardiac development and regeneration. However, reported CPCs are heterogeneous, and no gene has been identified to transiently mark undifferentiated CPCs throughout heart development. Here we show that Spalt-like gene 1 (Sall1), a zing-finger transcription factor, is expressed in undifferentiated CPCs giving rise to both left and right ventricles. Sall1 was transiently expressed in precardiac mesoderm contributing to the first heart field (left ventricle precursors) but not in the field itself. Similarly, Sall1 expression was maintained in the second heart field (outflow tract/right ventricle precursors) but not in cardiac cells. In vitro, high levels of Sall1 at mesodermal stages enhanced cardiomyogenesis, whereas its continued expression suppressed cardiac differentiation. Our study demonstrates that Sall1 marks CPCs in an undifferentiated state and regulates cardiac differentiation. These findings provide fundamental insights into CPC maintenance, which can be instrumental for CPC-based regenerative medicine. PMID- 26876453 TI - A computer program for fast and easy typing of a partial endoglucanase gene sequence into genospecies and sequevars 1&2 of the Ralstonia solanacearum species complex. AB - The phytopathogen Ralstonia solanacearum is a species complex that contains race 3 biovar 2 strains belonging to phylotype IIB sequevars 1 and 2 that are quarantined or select agent pathogens. Recently, the R. solanacearum species complex strains have been reclassified into three genospecies: R. solanacearum, Ralstonia pseudosolanacearum and Ralstonia syzygii. An unidentified R. solanacearum strain is considered a select agent in the US until proven to be a non-race 3 biovar 2 (non-phylotype IIB sequevars 1&2). Currently, sequevars of R. solanacearum species complex strains can only be determined by phylogenetic analysis of a partial endoglucanase (egl) sequence of approximately 700-bp in length. Such analysis, however, requires expert knowledge to properly trim the sequence, to include the correct reference strains, and to interpret the results. By comparing GenBank egl sequences of representative R. solanacearum species complex strains, we identified genospecies- and sequevar 1 and 2-specific single nucleotide polymorphisms (SNPs). We also designed primers to amplify a shorter, 526-bp, egl fragment from R. solanacearum species complex strains for easy sequencing of the amplicon, and to facilitate direct and specific amplification of egl from R. solanacearum-infected plant samples without the need of bacterial isolation. We wrote a computer program (Ralstonia solanacearum typing program) that analyzes a minimum 400-bp user-input egl sequence from a R. solanacearum strain for egl homology and SNP content to determine 1) whether it belongs to the R. solanacearum species complex, 2) if so, to which genospecies, and 3) whether it is of the sequevar type (sequevars 1 and 2) associated with the select agent/quarantined R. solanacearum strain. The program correctly typed all 371 tested egl sequences with known sequevars, obtained either from GenBank or through personal communication. Additionally, the program successfully typed 25 R. solanacearum strains in our collection with no prior sequevar information, as well as 4 strains in infected plant samples, using their partial egl sequences amplified and sequenced with primers designed in this study. The Ralstonia solanacearum typing program does not require expertise or specific knowledge to use, gives results in seconds, and provides data interpretation for the user. The program and primers can help expert or non-expert users to quickly type an unknown R. solanacearum species-complex strain and determine whether it is a highly regulated R. solanacearum strain. The program can also serve as a confirmation method, since it is the only method that can easily and directly determine whether the strain in question is a sequevar 1 or 2 strain of R. solanacearum. PMID- 26876451 TI - Epigenetic regulation of cardiac fibrosis. AB - Fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In the heart, fibrosis may be reparative, replacing areas of myocyte loss with a structural scar following infarction, or reactive, which is triggered in the absence of cell death and involves interstitial ECM deposition in response to long-lasting stress. Interstitial fibrosis can increase the passive stiffness of the myocardium, resulting in impaired relaxation and diastolic dysfunction. Additionally, fibrosis can lead to disruption of electrical conduction in the heart, causing arrhythmias, and can limit myocyte oxygen availability and thus exacerbate myocardial ischemia. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of small molecules that target epigenetic regulators as a means of treating fibrotic cardiac diseases. PMID- 26876452 TI - Neurobiological origin of spurious brain morphological changes: A quantitative MRI study. AB - The high gray-white matter contrast and spatial resolution provided by T1 weighted magnetic resonance imaging (MRI) has made it a widely used imaging protocol for computational anatomy studies of the brain. While the image intensity in T1-weighted images is predominantly driven by T1, other MRI parameters affect the image contrast, and hence brain morphological measures derived from the data. Because MRI parameters are correlates of different histological properties of brain tissue, this mixed contribution hampers the neurobiological interpretation of morphometry findings, an issue which remains largely ignored in the community. We acquired quantitative maps of the MRI parameters that determine signal intensities in T1-weighted images (R1 (=1/T1), R2 *, and PD) in a large cohort of healthy subjects (n = 120, aged 18-87 years). Synthetic T1-weighted images were calculated from these quantitative maps and used to extract morphometry features-gray matter volume and cortical thickness. We observed significant variations in morphometry measures obtained from synthetic images derived from different subsets of MRI parameters. We also detected a modulation of these variations by age. Our findings highlight the impact of microstructural properties of brain tissue-myelination, iron, and water content-on automated measures of brain morphology and show that microstructural tissue changes might lead to the detection of spurious morphological changes in computational anatomy studies. They motivate a review of previous morphological results obtained from standard anatomical MRI images and highlight the value of quantitative MRI data for the inference of microscopic tissue changes in the healthy and diseased brain. Hum Brain Mapp 37:1801-1815, 2016. (c) 2016 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID- 26876454 TI - Effects of inorganic arsenic exposure on glucose transporters and insulin receptor in the hippocampus of C57BL/6 male mice. AB - Children and adolescent populations chronically exposed to high doses of inorganic arsenic (iAs) in drinking water in some regions around the world have shown behavioral and memory deficits. Recent studies have also associated iAs exposure with dysregulation of glucose metabolism. The hippocampus is a cerebral region well known for its role in learning and memory. Studies in vitro and in vivo have shown that the hippocampus is vulnerable to iAs exposure, and to changes in glucose metabolism. The glucose transporters (GLUTs) and insulin receptor (IR) regulate glucose metabolism in brain; they are expressed by hippocampal cells, and alterations in these proteins have been associated with memory deficits. The aims of this study were to evaluate the effects of iAs exposure via drinking water (DW) on GLUT1, GLUT3 and insulin receptor (INSR) mRNA expression in the hippocampus, on performance in a spatial memory task, and on peripheral glucose regulation. C57Bl/6 male mice were exposed to 50 mg iAs/L via DW for one, two, or three months. The qRT-PCR analyses indicated that, compared to a control group, GLUT1 and GLUT3 mRNA levels were decreased, while INSR mRNA levels were increased in the hippocampus of iAs exposed animals. The levels of iAs and its methylated species in the hippocampus of the iAs-exposed group were significantly higher than in controls. Mice exposed to iAs learned the spatial task but showed increased latency to find the submerged platform 48 h after the last training session; these animals also showed dysregulation of peripheral glucose. These results suggest that the effects of iAs exposure on a spatial memory task performance could be mediated by disruptions of glucose regulation in the CNS. PMID- 26876455 TI - Low-level gestational exposure to mercury and maternal fish consumption: Associations with neurobehavior in early infancy. AB - BACKGROUND: Studies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy. METHODS: We assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates. RESULTS: Geometric mean of maternal and cord WBTHg were 0.64 and 0.72 MUg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p=0.04 for maternal WBTHg and p=0.03 for cord WBTHg), less need for special handling during the assessment (p=0.03 for cord WBTHg) and a trend of better attention (p=0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling. CONCLUSIONS: In a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption. PMID- 26876457 TI - The tradition of home nurse visiting: 40 years strong in JAN. PMID- 26876456 TI - Cognitive function at rest and during exercise following breakfast omission. AB - It has been suggested that breakfast omission, as opposed to breakfast consumption, has the detrimental effects on cognitive function. However, the effects of acute exercise following breakfast omission on cognitive function are poorly understood, particularly during exercise. The purpose of this study was to examine the interactive effects of breakfast and exercise on cognitive function. Ten participants completed cognitive tasks at rest and during exercise in the breakfast consumption or omission conditions. Blood glucose concentration was measured immediately after each cognitive task. We used cognitive tasks to assess working memory [Spatial Delayed Response (DR) task] and executive function [Go/No Go (GNG) task]. The participants cycled ergometer for 30 min while keeping their heart rate at 140 beats.min(-1). Accuracy of the GNG task was lower at rest in the breakfast omission condition than that in the breakfast consumption condition (Go trial: P=0.012; No-Go trial: P=0.028). However, exercise improved accuracy of the Go trial in the breakfast omission condition (P=0.013). Reaction time in the Go trial decreased during exercise relative to rest in both conditions (P=0.002), and the degree of decreases in reaction time was not different between conditions (P=0.448). Exercise and breakfast did not affect the accuracy of the Spatial DR task. The present results indicate that breakfast omission impairs executive function, but acute exercise improved executive function even after breakfast omission. It appears that beneficial effects of acute exercise on cognitive function are intact following breakfast omission. PMID- 26876458 TI - Induction Chemotherapy Followed by Chemo-intensity-modulated Radiotherapy for Locally Advanced Nasopharyngeal Cancer. AB - AIMS: To determine the toxicity and tumour control rates after chemo-intensity modulated radiotherapy (chemo-IMRT) for locally advanced nasopharyngeal cancers (LA-NPC). MATERIALS AND METHODS: Patients with LA-NPC were enrolled in a trial to receive induction chemotherapy followed by parotid-sparing chemo-IMRT. The primary site and involved nodal levels received 65 Gy in 30 fractions and at risk nodal levels received 54 Gy in 30 fractions. Incidence of >=grade 2 subjective xerostomia was the primary end point. Secondary end points included incidences of acute and late toxicities and survival outcomes. RESULTS: Forty-two patients with American Joint Committee on Cancer stages II (12%), III (26%) and IV (62%) (World Health Organization subtype: I [5%]; II [40%]; III [55%]) completed treatment between January 2006 and April 2010 with a median follow-up of 32 months. Incidences of >=grade 2 acute toxicities were: dysphagia 83%; xerostomia 76%; mucositis 97%; pain 76%; fatigue 99% and ototoxicity 12%. At 12 months, >=grade 2 subjective xerostomia was observed in 31%, ototoxicitiy in 13% and dysphagia in 4%. Two year locoregional control was 86.2% (95% confidence interval: 70.0-94.0) with 2 year progression-free survival at 78.4% (61.4-88.6) and 2 year overall survival at 85.9% (69.3-93.9). CONCLUSIONS: Chemo-IMRT for LA-NPC is feasible with good survival outcomes. At 1 year, 31% experience >=grade 2 subjective xerostomia. PMID- 26876459 TI - Emergency Responses and Health Consequences after the Fukushima Accident; Evacuation and Relocation. AB - The Fukushima accident was a compounding disaster following the strong earthquake and huge tsunami. The direct health effects of radiation were relatively well controlled considering the severity of the accident, not only among emergency workers but also residents. Other serious health issues include deaths during evacuation, collapse of the radiation emergency medical system, increased mortality among displaced elderly people and public healthcare issues in Fukushima residents. The Fukushima mental health and lifestyle survey disclosed that the Fukushima accident caused severe psychological distress in the residents from evacuation zones. In addition to psychiatric and mental health problems, there are lifestyle-related problems such as an increase proportion of those overweight, an increased prevalence of hypertension, diabetes mellitus and dyslipidaemia and changes in health-related behaviours among evacuees; all of which may lead to an increased cardiovascular disease risk in the future. The effects of a major nuclear accident on societies are diverse and enduring. The countermeasures should include disaster management, long-term general public health services, mental and psychological care, behavioural and societal support, in addition to efforts to mitigate the health effects attributable to radiation. PMID- 26876460 TI - Active Surveillance of Prostate Cancer in a Community Practice: How to Measure, Manage, and Improve? AB - OBJECTIVE: To measure past active surveillance (AS) adoption rates, institute the best practice, and measure the AS adoption rates following implementation. We report our findings over a 3-year period. METHODS: Patient prostate needle biopsy and treatment data from the period August 2011 to August 2014 were retrieved from an integrated electronic medical records (Allscripts) and stored in a Microsoft Access database for analysis. Structured data were queried using the automated software program WizMD and unstructured data were abstracted by manual review. AS adoption was calculated according to four different selection criteria. Between 2013 and 2014, physicians at Genesis Healthcare Partners (GHP) underwent an educational training program on the University of California, San Diego/GHP AS best practice for managing low-risk prostate cancer patients and were provided report cards on their AS adoption and comparative reporting. RESULTS: AS adoption increased for the 3 years of the study. AS adoption for all newly diagnosed patients managed at GHP increased from 12.9% to 14.74%. AS adoption for patients with low-risk prostate cancer (as defined by the National Comprehensive Cancer Network) increased from 31.90% to 58.46% from year 1 to year 3 of the study (P < .001), and AS adoption for the most strict (restrictive) criteria increased from 43.75% to 82.61% (P < .001) after the educational and comparative reporting intervention. CONCLUSION: These data highlight the potential benefit of physician education and comparative reporting to enhance AS adoption. AS adoption rates vary according to selection criteria used for analysis. Carefully selected outcomes from evidence-based guidelines have the potential to enhance medical quality. PMID- 26876461 TI - Adynamic Graciloplasty With a Pedicled Gracilis Muscle Flap Wrapped Around Bulbar Urethra for Treatment of Male Acquired Urinary Incontinence. AB - OBJECTIVE: To evaluate the efficacy of adynamic gracilis urethral myoplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra for treatment of male acquired urinary incontinence. PATIENTS AND METHODS: Twenty-four patients with acquired urinary incontinence (8 after radical prostatectomy, 7 after transurethral resection of the prostate, and 9 after posterior urethroplasty) were included in our study. Eighteen of these patients (75.0%) had mild to moderate urinary incontinence, and 6 (25.0%) had severe urinary incontinence. All patients received adynamic gracilis urethral myoplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra and had a close follow-up. RESULTS: The mean postoperative maximum urethral pressure after the gracilis muscle wrapped around bulbar urethra was significantly higher than that of the preoperative measurements (P <.05). After a mean follow-up of 31.5 months (6-64 months), 18 patients were cured, 4 patients improved, and 2 patients were considered failures. The total cure rate was 75.0% (18 of 24). Five out of 6 patients with severe incontinence did not have a great success. CONCLUSION: A pedicled gracilis muscle flap wrapped around bulbar urethra can raise the urethral pressure. Adynamic graciloplasty with a pedicled gracilis muscle flap wrapped around bulbar urethra is a safe and effective surgical option in the treatment of male patients with mild to moderate incontinence, but is not suitable for severe incontinence. PMID- 26876462 TI - PLK-1 Silencing in Bladder Cancer by siRNA Delivered With Exosomes. AB - OBJECTIVE: To use exosomes as a vector to deliver small interfering ribonucleic acid (siRNA) to silence the polo-like kinase 1 (PLK-1) gene in bladder cancer cells. MATERIALS AND METHODS: Exosomes were isolated from both human embryonic kidney 293 (HEK293) cell and mesenchymal stem cell (MSC) conditioned media. Fluorescently labeled exosomes were co-cultured with bladder cancer and normal epithelial cells and uptake was quantified by image cytometry. PLK-1 siRNA and negative control siRNA were loaded into HEK293 and MSC exosomes using electroporation. An invasive bladder cancer cell line (UMUC3) was co-cultured with the electroporated exosomes. Quantitative reverse transcriptase polymerase chain reaction was performed. Protein analysis was performed by Western blot. Annexin V staining and MTT assays were used to investigate effects on apoptosis and viability. RESULTS: Bladder cancer cell lines internalize an increased percentage of HEK293 exosomes when compared to normal bladder epithelial cells. Treatment of UMUC3 cells with exosomes electroporated with PLK-1 siRNA achieved successful knockdown of PLK-1 mRNA and protein when compared to cells treated with negative control exosomes. CONCLUSION: HEK293 and MSC exosomes were effectively used as a delivery vector to transport PLK-1 siRNA to bladder cancer cells in vitro, resulting in selective gene silencing of PLK-1. The use of exosomes as a delivery vector for potential intravesical therapy is attractive. PMID- 26876463 TI - Laparoscopic Resection of a Renal Hilar Pheochromocytoma in an Adolescent With a Circumaortic Left Renal Vein. AB - Pheochromocytoma is a neuroendocrine tumor that usually develops from the chromaffin cells in the adrenal medulla. Extra-adrenal pheochromocytomas arise in the neural crest cells of the retroperitoneal paraganglia and renal hilum is a common site for their occurrence. We describe a 17-year-old boy, whom we believe to be the first reported case of successful laparoscopic resection of a renal hilar extra-adrenal pheochromocytoma in the setting of a circumaortic left renal vein. PMID- 26876464 TI - Giant Fungating Basal Cell Carcinoma of the Scrotum. AB - We present an unusual case of basal cell carcinoma (BCC) arising from a non-sun exposed area. The patient was 69-year-old male with an enlarging giant fungating mass protruding from his scrotum for which he did not seek medical treatment until recently. The mass did not involve the scrotum or epididymis and was confirmed on ultrasound. The patient underwent wide surgical excision and was diagnosed with BCC of the scrotum. Scrotal BCC appears to be more aggressive and more likely to metastasize compared with lesions arising from other areas of the body. PMID- 26876465 TI - Outcomes of Surgical Management of Men With Peyronie's Disease With Hourglass Deformity. AB - OBJECTIVE: To investigate the outcomes of two surgical interventions for Peyronie's disease (PD) with hourglass deformity: partial excision and grafting (PEG) or inflatable penile prosthesis (IPP) implantation. MATERIALS AND METHODS: Retrospective data were collected from two centers: Technical University of Munich (PEG) and Tulane University Medical Center (IPP). Collected variables included patient demographics, sexual function, penile vascular measurements, and treatment outcomes. RESULTS: A total of 50 PD patients with hourglass deformity (26 PEG [group 1] and 24 IPP [group 2]) were included in this study. Patients in group 1 had higher mean preoperative Sexual Health Inventory for Men scores (22.2 vs 10.3, P < 0001), required less erectile dysfunction treatment (35% vs 79%, P = .005), and had more nonvascular etiology (77% vs 21%, P < .0001). There were no intraoperative complications, 2 patients in group 1 had postoperative glans hypoesthesia, and 1 patient in group 2 required surgical revision. All patients in both groups had significant >=20% improvements in penile curvature with mean changes of 68.1 degrees (12.7) in group 1 and 49.6 degrees (13.5) in group 2, P < .0001. Resolution of hourglass deformity was achieved in 85% of patients in group 1 and 100% of patients in group 2, P = .045. The mean postoperative change in Sexual Health Inventory for Men score was -0.3 (1.3) in group 1 and 16.7 (4.7) in group 2, P < .0001. CONCLUSION: Both options provide excellent outcomes for well selected patients with PD and an hourglass deformity. PEG can be offered to patients with good erectile function, whereas the IPP remains the preferred option for patients with poor erections. PMID- 26876466 TI - Impact of Changing Trends in Medical Therapy on Transurethral Resection of the Prostate: Two Decades of Change in China. AB - OBJECTIVE: To retrospectively assess that over the 2 decades, whether medical therapy has changed indications, patient characteristics, and outcomes in men undergoing transurethral resection of the prostate (1992-2013). METHODS: At our institution, medical history of all patients undergoing surgery before 1998, between 2001 and 2003, and between 2011 and 2013 was reviewed. Patient demographics, preoperative clinical profile, clinical management, and operative complications were assessed. RESULTS: A total of 1157 patients were enrolled in the study. Mean ages of patients increased from 67.0 to 70.4 years old over the past 2 decades. Furthermore, comorbidities increased significantly as well. Although prostate size and weight of resected tissue increased from 57.3 to 92.3 g and from 24.3 to 36.6 g, the surgical time decreased from 78.21 to 72.29 minutes. From 2011 to 2013, patients undergoing surgery had their catheters remove earlier (from 5.7 to 4.5 days), whose postoperative days in hospital were shorter (from 9.3 to 4.4 days). Although operative complications decreased from 12.3% to 5.7%, especially bleeding, re-operation due to bleeding increased from 0.4% to 2.7%. Moreover, no statistical difference was observed in operative complications between patients with medical therapy and those without medical therapy. CONCLUSION: The increasing application of medical therapy resulted in surgical interventions delay. The prostate size was significantly greater, as was the weight of resected tissue. Although patients with medication were older with more comorbidities and larger prostates, surgical technique advancements have benefited them and transurethral resection of the prostate is still considered as a safe and recommendable surgical treatment. PMID- 26876467 TI - Traumatic neuroma on the digital tip: Immunohistochemical analysis of inflammatory signaling pathways. PMID- 26876468 TI - Self-assembled platinum nanoparticles on sulfonic acid-grafted graphene as effective electrocatalysts for methanol oxidation in direct methanol fuel cells. AB - In this article, sulfonic acid-grafted reduced graphene oxide (S-rGO) were synthesized using a one-pot method under mild conditions, and used as Pt catalyst supports to prepare Pt/S-rGO electrocatalysts through a self-assembly route. The structure, morphologies and physicochemical properties of S-rGO were examined in detail by techniques such as atomic force microscope (AFM), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). The S-rGO nanosheets show excellent solubility and stability in water and the average particle size of Pt nanoparticles supported on S-rGO is ~3.8 nm with symmetrical and uniform distribution. The electrocatalytic properties of Pt/S-rGO were investigated for methanol oxidation reaction (MOR) in direct methanol fuel cells (DMFCs). In comparison to Pt supported on high surface area Vulcan XC-72 carbon (Pt/VC) and Pt/rGO, the Pt/S-rGO electrocatalyst exhibits a much higher electrocatalytic activity, faster reaction kinetics and a better stability. The results indicate that Pt/S-rGO is a promising and effective electrocatalyst for MOR of DMFCs. PMID- 26876469 TI - H1N1 influenza presenting as severe acute pancreatitis and multiorgan dysfunction. PMID- 26876470 TI - Posttraumatic pneumatization of the optic sheath. PMID- 26876471 TI - Orienting attention to visual or verbal/auditory imagery differentially impairs the processing of visual stimuli. AB - When attention is oriented toward inner thoughts, as spontaneously occurs during mind wandering, the processing of external information is attenuated. However, the potential effects of thought's content regarding sensory attenuation are still unknown. The present study aims to assess if the representational format of thoughts, such as visual imagery or inner speech, might differentially affect the sensory processing of external stimuli. We recorded the brain activity of 20 participants (12 women) while they were exposed to a probe visual stimulus in three different conditions: executing a task on the visual probe (externally oriented attention), and two conditions involving inward-turned attention i.e. generating inner speech and performing visual imagery. Event-related potentials results showed that the P1 amplitude, related with sensory response, was significantly attenuated during both task involving inward attention compared with external task. When both representational formats were compared, the visual imagery condition showed stronger attenuation in sensory processing than inner speech condition. Alpha power in visual areas was measured as an index of cortical inhibition. Larger alpha amplitude was found when participants engaged in an internal thought contrasted with the external task, with visual imagery showing even more alpha power than inner speech condition. Our results show, for the first time to our knowledge, that visual attentional processing to external stimuli during self-generated thoughts is differentially affected by the representational format of the ongoing train of thoughts. PMID- 26876472 TI - Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism. AB - The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the alpha1/alpha5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of alpha1 and alpha5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced alpha5 but not alpha1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by alpha5 and not alpha1 subtype. We suggest that reduced alpha5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates. PMID- 26876474 TI - Weight restoration therapy rapidly reverses cortical thinning in anorexia nervosa: A longitudinal study. AB - Structural magnetic resonance imaging studies have documented reduced gray matter in acutely ill patients with anorexia nervosa to be at least partially reversible following weight restoration. However, few longitudinal studies exist and the underlying mechanisms of these structural changes are elusive. In particular, the relative speed and completeness of brain structure normalization during realimentation remain unknown. Here we report from a structural neuroimaging study including a sample of adolescent/young adult female patients with acute anorexia nervosa (n=47), long-term recovered patients (n=34), and healthy controls (n=75). The majority of acutely ill patients were scanned longitudinally (n=35): at the beginning of standardized weight restoration therapy and again after partial weight normalization (>10% body mass index increase). High resolution structural images were processed and analyzed with the longitudinal stream of FreeSurfer software to test for changes in cortical thickness and volumes of select subcortical regions of interest. We found globally reduced cortical thickness in acutely ill patients to increase rapidly (0.06 mm/month) during brief weight restoration therapy (~3 months). This significant increase was predicted by weight restoration alone and could not be ascribed to potentially mediating factors such as duration of illness, hydration status, or symptom improvements. By comparing cortical thickness in partially weight restored patients with that measured in healthy controls, we confirmed that cortical thickness had normalized already at follow-up. This pattern of thinning in illness and rapid normalization during weight rehabilitation was largely mirrored in subcortical volumes. Together, our findings indicate that structural brain insults inflicted by starvation in anorexia nervosa may be reversed at a rate much faster than previously thought if interventions are successful before the disorder becomes chronic. This provides evidence drawing previously speculated mechanisms such as (de-)hydration and neurogenesis into question and suggests that neuronal and/or glial remodeling including changes in macromolecular content may underlie the gray matter alterations observed in anorexia nervosa. PMID- 26876473 TI - In vivo quantification of demyelination and recovery using compartment-specific diffusion MRI metrics validated by electron microscopy. AB - There is a need for accurate quantitative non-invasive biomarkers to monitor myelin pathology in vivo and distinguish myelin changes from other pathological features including inflammation and axonal loss. Conventional MRI metrics such as T2, magnetization transfer ratio and radial diffusivity have proven sensitivity but not specificity. In highly coherent white matter bundles, compartment specific white matter tract integrity (WMTI) metrics can be directly derived from the diffusion and kurtosis tensors: axonal water fraction, intra-axonal diffusivity, and extra-axonal radial and axial diffusivities. We evaluate the potential of WMTI to quantify demyelination by monitoring the effects of both acute (6weeks) and chronic (12weeks) cuprizone intoxication and subsequent recovery in the mouse corpus callosum, and compare its performance with that of conventional metrics (T2, magnetization transfer, and DTI parameters). The changes observed in vivo correlated with those obtained from quantitative electron microscopy image analysis. A 6-week intoxication produced a significant decrease in axonal water fraction (p<0.001), with only mild changes in extra axonal radial diffusivity, consistent with patchy demyelination, while a 12-week intoxication caused a more marked decrease in extra-axonal radial diffusivity (p=0.0135), consistent with more severe demyelination and clearance of the extra axonal space. Results thus revealed increased specificity of the axonal water fraction and extra-axonal radial diffusivity parameters to different degrees and patterns of demyelination. The specificities of these parameters were corroborated by their respective correlations with microstructural features: the axonal water fraction correlated significantly with the electron microscopy derived total axonal water fraction (rho=0.66; p=0.0014) but not with the g ratio, while the extra-axonal radial diffusivity correlated with the g-ratio (rho=0.48; p=0.0342) but not with the electron microscopy derived axonal water fraction. These parameters represent promising candidates as clinically feasible biomarkers of demyelination and remyelination in the white matter. PMID- 26876476 TI - Effects of simulated interpersonal touch and trait intrinsic motivation on the error-related negativity. AB - The error-related negativity (ERN or Ne) is a negative event-related brain potential that peaks about 20-100 ms after people perform an incorrect response in choice reaction time tasks. Prior research has shown that the ERN may be enhanced by situational and dispositional factors that promote intrinsic motivation. Building on and extending this work the authors hypothesized that simulated interpersonal touch may increase task engagement and thereby increase ERN amplitude. To test this notion, 20 participants performed a Go/No-Go task while holding a teddy bear or a same-sized cardboard box. As expected, the ERN was significantly larger when participants held a teddy bear rather than a cardboard box. This effect was most pronounced for people high (rather than low) in trait intrinsic motivation, who may depend more on intrinsically motivating task cues to maintain task engagement. These findings highlight the potential benefits of simulated interpersonal touch in stimulating attention to errors, especially among people who are intrinsically motivated. PMID- 26876478 TI - Importance of visual inputs quality for postural stability in strabismic children. AB - OBJECTIVE: The first goal of the present study is to analyze the postural control in strabismic children in four different visual conditions (eyes open, eyes closed and monocular viewing with squint eye and non-squint eye). Secondly, we wish to explore the effect of strabismus surgery in postural control. METHOD: Postural stability was recorded with a platform (TechnoConcept) in 23 strabismic children aged from 4.4 to 14.8 years old (mean age: 8.4 years); 12 of these children were also examined at least two months after strabismus surgery. We analyzed the surface, the length, and the mean speed of the Center of Pressure displacement (CdP), and we calculated the Romberg's Quotient (that is for each postural parameter the ratio between eyes closed relative to eyes open). RESULTS: Strabismic children are significantly more stable when they can use their visual information to control their posture. Also, postural stability was better when the non-squint eye was viewing. For the first time, we observed the important role of vision (by calculating Romberg's Quotient) in strabismic children with binocular vision in comparison of strabismic children without binocular vision. Finally, we found that eye surgery improves postural stability. CONCLUSION: Strabismic children use visual inputs to control their posture. Moreover, binocular vision plays an important role in postural control. Strabismus surgery improves postural stability. SIGNIFICANCE: Visual inputs from the non-squint eye and binocular vision are important to control stability. PMID- 26876477 TI - Epigenetic regulation of mitochondrial function in neurodegenerative disease: New insights from advances in genomic technologies. AB - The field of mitochondrial epigenetics has received increased attention in recent years and changes in mitochondrial DNA (mtDNA) methylation has been implicated in a number of diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis. However, current publications have been limited by the use of global or targeted methods of measuring DNA methylation. In this review, we discuss current findings in mitochondrial epigenetics as well as its potential role as a regulator of mitochondria within the brain. Finally, we summarize the current technologies best suited to capturing mtDNA methylation, and how a move towards whole epigenome sequencing of mtDNA may help to advance our current understanding of the field. PMID- 26876475 TI - Age-related changes in binding of the D2/3 receptor radioligand [(11)C](+)PHNO in healthy volunteers. AB - OBJECTIVE: Previous imaging studies with positron emission tomography (PET) have reliably demonstrated an age-associated decline in the dopamine system. Most of these studies have focused on the densities of dopamine receptor subtypes D2/3R (D2R family) in the striatum using antagonist radiotracers that are largely nonselective for D2R vs. D3R subtypes. Therefore, less is known about any possible age effects in D3-rich extrastriatal areas such as the substantia nigra/ventral tegmental area (SN/VTA) and hypothalamus. This study sought to investigate whether the receptor availability measured with [(11)C](+)PHNO, a D3R preferring agonist radiotracer, also declines with age. METHODS: Forty-two healthy control subjects (9 females, 33 males; age range 19-55 years) were scanned with [(11)C](+)PHNO using a High Resolution Research Tomograph (HRRT). Parametric images were computed using the simplified reference tissue model (SRTM2) with cerebellum as the reference region. Binding potentials (BPND) were calculated for the amygdala, caudate, hypothalamus, pallidum, putamen, SN/VTA, thalamus, and ventral striatum and then confirmed at the voxel level with whole brain parametric images. RESULTS: Regional [(11)C](+)PHNO BPND displayed a negative correlation between receptor availability and age in the caudate (r= 0.56, corrected p=0.0008) and putamen (r=-0.45, corrected p=0.02) in healthy subjects (respectively 8% and 5% lower per decade). No significant correlations with age were found between age and other regions (including the hypothalamus and SN/VTA). Secondary whole-brain voxel-wise analysis confirmed these ROI findings of negative associations and further identified a positive correlation in midbrain (SN/VTA) regions. CONCLUSION: In accordance with previous studies, the striatum (an area rich in D2R) is associated with age-related declines of the dopamine system. We did not initially find evidence of changes with age in the SN/VTA and hypothalamus, areas previously found to have a predominantly D3R signal as measured with [(11)C](+)PHNO. A secondary analysis did find a significant positive correlation in midbrain (SN/VTA) regions, indicating that there may be differential effects of aging, whereby D2R receptor availability decreases with age while D3R availability stays unchanged or is increased. PMID- 26876479 TI - Durable, superoleophobic polymer-nanoparticle composite surfaces with re-entrant geometry via solvent-induced phase transformation. AB - Superoleophobic plastic surfaces are useful in a wide variety of applications including anti-fouling, self-cleaning, anti-smudge, and low-drag. Existing examples of superoleophobic surfaces typically rely on poorly adhered coatings or delicate surface structures, resulting in poor mechanical durability. Here, we report a facile method for creating re-entrant geometries desirable for superoleophobicity via entrapment of nanoparticles in polycarbonate surfaces. Nanoparticle incorporation occurs during solvent-induced swelling and subsequent crystallization of the polymer surface. The resulting surface was found to comprise of re-entrant structures, a result of the nanoparticle agglomerates acting as nucleation points for polymer crystallization. Examples of such surfaces were further functionalized with fluorosilane to result in a durable, super-repellent surface. This method of impregnating nanoparticles into polymer surfaces could prove useful in improving the anti-bacterial, mechanical, and liquid-repellent properties of plastic devices. PMID- 26876480 TI - Co-delivery of doxorubicin and curcumin by pH-sensitive prodrug nanoparticle for combination therapy of cancer. AB - Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff's base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff's base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy. PMID- 26876481 TI - Complete genome of Pseudomonas sp. strain L10.10, a psychrotolerant biofertilizer that could promote plant growth. AB - Pseudomonas sp. strain L10.10 (=DSM 101070) is a psychrotolerant bacterium which was isolated from Lagoon Island, Antarctica. Analysis of its complete genome sequence indicates its possible role as a plant-growth promoting bacterium, including nitrogen-fixing ability and indole acetic acid (IAA)-producing trait, with additional suggestion of plant disease prevention attributes via hydrogen cyanide production. PMID- 26876482 TI - Effects of Narrow-band IR-A and of Water-Filtered Infrared A on Fibroblasts. AB - Exposures of the skin with electromagnetic radiation of wavelengths between 670 nm and 1400 nm are often used as a general treatment to improve wound healing and reduce pain, for example, in chronic diabetic skin lesions. We investigated the effects of water-filtered infrared A (wIRA) and of narrow-band IR-A provided by a light-emitting diode LED (LED-IR-A) irradiation in vitro on 3T3 fibroblast cultures under defined conditions with and without glyoxal administration. Glyoxal triggers the formation of advanced glycation end products, thereby mimicking a diabetic metabolic state. Cell viability and apoptotic changes were determined by flow cytometry after vital staining with Annexin V, YO-PRO-1 and propidium iodide (PI), and by SubG1 assay. Mitochondrial function and oxidative stress were examined by vital staining for radical production, mitochondrial membrane potential (MMP) and the ratio of reduced-to-oxidized glutathione (GSH/GSSG). The metabolic state was monitored by a resazurin conversion assay. The numbers of apoptotic cells were reduced in cultures irradiated with wIRA or LED-IR-A. More mitochondria showed a well-polarized MMP after wIRA irradiation in glyoxal damaged cells. LED-IR-A treatment specifically restored the GSH/GSSG ratio. The immediate positive effects of wIRA and LED-IR-A observed in living cells, particularly on mitochondria, reflect the therapeutic benefits of wIRA and LED-IR-A. PMID- 26876483 TI - Ribosomal small subunit domains radiate from a central core. AB - The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2'OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit. PMID- 26876484 TI - Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis. AB - Ulcerative colitis (UC) is a major type of idiopathic inflammatory bowel disease (IBD). Immunosuppressive therapies are used to treat IBD patients. Clinicians have strong concerns about using immunosuppressive therapies for IBD patients with hepatitis B virus (HBV) infection because aggressive immunosuppressive therapy can promote reactivation of HBV. For that reason, physicians hesitate to use steroids or other immunosuppressive drugs for IBD patients with HBV infection. Granulocyte monocyte apheresis (GMA) is a safe and effective therapy for UC patients. In Japan, a maximum of 11 sessions of GMA are allowed for moderate-to-severe, steroid-resistant UC patients. However, the effects of GMA on HBV remain unclear. This case report describes a 39-year-old man with active UC complicated by HBV infection. Although his symptoms improved with steroid treatment while under entecavir therapy, clinical remission could not be maintained after the steroid dosage was decreased, so GMA was started. After GMA initiation, the frequency of diarrhea decreased and his symptoms improved, and the steroid dosage could be decreased. During the course of GMA, the patient did not experience deterioration in his hepatitis and the HBV DNA level gradually decreased, although GMA itself did not affect the HBV DNA level during each session of GMA. Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity. J. Clin. Apheresis 31:584-586, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26876485 TI - Field studies versus database studies on the risks and benefits of medication use during pregnancy: Distinct pieces of the same puzzle. AB - Over the past two decades, findings on medication use during pregnancy have been accumulating from observational data. Generally, field studies with prospective recruitment of subjects have better outcome ascertainment, and more control on the longitudinal collection of data, but have lower sample sizes and thus they often lack statistical power to detect increased risks for rare events such as major congenital malformations. In addition, given the rarity of specific drug exposures in a population, even relatively common outcomes, such as low birth weight, may become rare in combination with the specific exposure. On the other hand, administrative databases usually provide larger samples and thus increased statistical power, decrease the probability of selection and recall bias, but often have missing data on potential confounders. Hence, debate amongst researchers, regulators and public health officials has been ongoing with regard to the most appropriate study populations for perinatal epidemiologic research. With this commentary, we aim to highlight the importance of both study populations, which can make complementary and crucial contributions to the iterative determination of causality as well as discuss basic epidemiologic principles that need to be applied in the field of perinatal pharmacoepidemiology for the purpose of causality assessment. This is relevant at present given that the United States Food and Drug Administration (US FDA) has modified their medication label requirements, especially given the international importance of these modifications. PMID- 26876486 TI - High resolution atomic force microscopy of double-stranded RNA. AB - Double-stranded (ds) RNA mediates the suppression of specific gene expression, it is the genetic material of a number of viruses, and a key activator of the innate immune response against viral infections. The ever increasing list of roles played by dsRNA in the cell and its potential biotechnological applications over the last decade has raised an interest for the characterization of its mechanical properties and structure, and that includes approaches using Atomic Force Microscopy (AFM) and other single-molecule techniques. Recent reports have resolved the structure of dsDNA with AFM at unprecedented resolution. However, an equivalent study with dsRNA is still lacking. Here, we have visualized the double helix of dsRNA under near-physiological conditions and at sufficient resolution to resolve the A-form sub-helical pitch periodicity. We have employed different high-sensitive force-detection methods and obtained images with similar spatial resolution. Therefore, we show here that the limiting factors for high-resolution AFM imaging of soft materials in liquid medium are, rather than the imaging mode, the force between the tip and the sample and the sharpness of the tip apex. PMID- 26876489 TI - Are hypertensive women at additional risk of ischaemic heart disease from physically demanding work? AB - BACKGROUND: The combination of hypertension and high physical activity at work may increase blood pressure considerably and increase the risk of atherosclerosis and thereby ischaemic heart disease (IHD), but only a few studies in men, and none among women, have examined this topic. DESIGN: This was a prospective cohort study. METHODS: In 1993, 12,093 female nurses from the Danish Nurse Cohort Study, aged 45-64 years answered a baseline questionnaire on physical activity at work, history of hypertension, a selection of known risk factors for IHD and occupational factors. Information on incident IHD from baseline to 2008 was retrieved by individual linkage to the National Register of Hospital Discharges. RESULTS: In a fully adjusted Cox model, hypertensive nurses with high physical activity at work had nearly three times higher risk of IHD (hazard ratio (HR) 2.87 (95% confidence interval (CI) 2.12-3.87)) compared to normotensive nurses with moderate physical activity at work. Significant additive interaction between physical activity at work and hypertension was found measured by the relative excess risk due to additive interaction (RERI) (1.20 (95% CI 0.26-2.14), and in an additive hazards model. Hypertensive nurses with high physical activity at work had 60 additional cases of IHD per 10,000 person years compared to normotensive nurses with moderate physical activity at work (60.0 (95% CI 38.1 81.9; p < 0.001)), of which more than half was explained by additive interaction (40.7 (95% CI 11.7-69.7; p = 0.006)). No multiplicative interaction (p = 0.249) was found. CONCLUSIONS: This study among Danish nurses indicated that hypertensive women may be at particular high risk of IHD from physically demanding work. PMID- 26876487 TI - The histone variant H2A.X is a regulator of the epithelial-mesenchymal transition. AB - The epithelial-mesenchymal transition (EMT), considered essential for metastatic cancer, has been a focus of much research, but important questions remain. Here, we show that silencing or removing H2A.X, a histone H2A variant involved in cellular DNA repair and robust growth, induces mesenchymal-like characteristics including activation of EMT transcription factors, Slug and ZEB1, in HCT116 human colon cancer cells. Ectopic H2A.X re-expression partially reverses these changes, as does silencing Slug and ZEB1. In an experimental metastasis model, the HCT116 parental and H2A.X-null cells exhibit a similar metastatic behaviour, but the cells with re-expressed H2A.X are substantially more metastatic. We surmise that H2A.X re-expression leads to partial EMT reversal and increases robustness in the HCT116 cells, permitting them to both form tumours and to metastasize. In a human adenocarcinoma panel, H2A.X levels correlate inversely with Slug and ZEB1 levels. Together, these results point to H2A.X as a regulator of EMT. PMID- 26876488 TI - Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder. AB - Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure. PMID- 26876491 TI - Cell phone use is associated with an inflammatory cytokine profile of parotid gland saliva. AB - BACKGROUND: There is controversy on the effects of the non-ionizing radiation emitted by cell phones on cellular processes and the impact of such radiation exposure on health. The purpose of this study was to investigate whether cell phone use alters cytokine expression in the saliva produced by the parotid glands. METHODS: Cytokine expression profile was determined by enzyme linked immuno sorbent assay (ELISA) in the saliva produced by the parotid glands in healthy volunteers, and correlated with self-reported cell phone use and laterality. RESULTS: The following parameters were determined, in 83 Brazilian individuals in saliva produced by the parotid glands comparing the saliva from the gland exposed to cell phone radiation (ipsilateral) to that from the contralateral parotid: salivary flow, total protein concentration, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 10 (IL-10), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) salivary levels by ELISA. After multiple testing correction, decreased IL-10 and increased IL-1beta salivary levels in the ipsilateral side compared with the contralateral side (P < 0.05) were detected. Subjects who used cell phones for more than 10 years presented higher differences between IL-10 levels in ipsilateral versus contralateral parotids (P = 0.0012). No difference was observed in any of the tested parameters in correlation with cell phone monthly usage in minutes. CONCLUSION: The exposure of parotid glands to cell phones can alter salivary IL 10 and IL-1beta levels, consistent with a pro-inflammatory microenvironment that may be related to heat production. PMID- 26876490 TI - Serotonin 2A receptor agonist binding in the human brain with [(11)C]Cimbi-36: Test-retest reproducibility and head-to-head comparison with the antagonist [(18)F]altanserin. AB - INTRODUCTION: [(11)C]Cimbi-36 is a recently developed serotonin 2A (5-HT2A) receptor agonist positron emission tomography (PET) radioligand that has been successfully applied for human neuroimaging. Here, we investigate the test-retest variability of cerebral [(11)C]Cimbi-36 PET and compare [(11)C]Cimbi-36 and the 5 HT2A receptor antagonist [(18)F]altanserin. METHODS: Sixteen healthy volunteers (mean age 23.9 +/- 6.4years, 6 males) were scanned twice with a high resolution research tomography PET scanner. All subjects were scanned after a bolus of [(11)C]Cimbi-36; eight were scanned twice to determine test-retest variability in [(11)C]Cimbi-36 binding measures, and another eight were scanned after a bolus plus constant infusion with [(18)F]altanserin. Regional differences in the brain distribution of [(11)C]Cimbi-36 and [(18)F]altanserin were assessed with a correlation of regional binding measures and with voxel-based analysis. RESULTS: Test-retest variability of [(11)C]Cimbi-36 non-displaceable binding potential (BPND) was consistently <5% in high-binding regions and lower for reference tissue models as compared to a 2-tissue compartment model. We found a highly significant correlation between regional BPNDs measured with [(11)C]Cimbi-36 and [(18)F]altanserin (mean Pearson's r: 0.95 +/- 0.04) suggesting similar cortical binding of the radioligands. Relatively higher binding with [(11)C]Cimbi-36 as compared to [(18)F]altanserin was found in the choroid plexus and hippocampus in the human brain. CONCLUSIONS: Excellent test-retest reproducibility highlights the potential of [(11)C]Cimbi-36 for PET imaging of 5-HT2A receptor agonist binding in vivo. Our data suggest that Cimbi-36 and altanserin both bind to 5 HT2A receptors, but in regions with high 5-HT2C receptor density, choroid plexus and hippocampus, the [(11)C]Cimbi-36 binding likely represents binding to both 5 HT2A and 5-HT2C receptors. PMID- 26876492 TI - A painful swelling of the mandible. PMID- 26876493 TI - Surgical evaluation of panoramic radiography and cone beam computed tomography for therapy planning of bisphosphonate-related osteonecrosis of the jaws. AB - OBJECTIVES: The purpose of this retrospective study was to compare the clinical significance of panoramic radiography (orthopantomography [OPTG]) and cone beam computed tomography (CBCT) for therapy planning of bisphosphonate-related osteonecrosis of the jaw (BRONJ) by surgeons. STUDY DESIGN: Using standardized questionnaire, eight maxillofacial surgeons evaluated intraoral photographs of the clinical situation of 14 patients with BRONJ as well as the corresponding radiographic images (OPTG, CBCT). The presence of five typical BRONJ signs (bone remodeling, periosteal reaction, osteosclerosis, sequestra, and continuity of cortical bone) was evaluated with OPTG and CBCT. The influence of radiologic information on therapy decision was examined as well. RESULTS: On the basis of the information from intraoral photographs only, seven of the eight surgeons indicated that an additional radiographic examination was necessary for further therapy planning. For evaluation of the five radiographic BRONJ signs, CBCT provided significantly better values compared with OPTG (all P < .05). A before and-after comparison showed that four of the eight surgeons changed their therapy concept after having three-dimensional CBCT information. The majority (6 of 8) of the surgeons considered that an additional CBCT was required for therapy planning, even after having studied the clinical photographs and OPTG images. CONCLUSION: These data demonstrate a significant advantage of CBCT over OPTG for surgeons with regard to therapeutic planning for BRONJ. PMID- 26876494 TI - Droplet-mediated formation of embedded GaAs nanowires in MBE GaAs(1-x)Bi(x) films. AB - We have examined the morphology and composition of embedded nanowires that can be formed during molecular beam epitaxy of GaAs(1-x)Bi(x) using high angle annular dark field ('Z-contrast') imaging in an aberration-corrected scanning transmission electron microscope. Samples were grown in Ga-rich growth conditions on a stationary GaAs substrate. Ga-rich droplets are observed on the surface with lateral trails extending from the droplet in the [110] direction. Cross-sectional scanning transmission electron microscopy of the film reveals epitaxial nanowire structures of composition ~GaAs embedded in the GaAs(1-x)Bi(x) epitaxial layers. These nanowires extend from a surface droplet to the substrate at a shallow angle of inclination (~4 degrees ). They typically are 4 MUm long and have a lens shaped cross section with major and minor axes dimensions of 800 and 120 nm. The top surface of the nanowires exhibits a linear trace in longitudinal cross section, across which the composition change from ~GaAs to GaAs(1-x)Bi(x) appears abrupt. The bottom surfaces of the nanowires appear wavy and the composition change appears to be graded over ~25 nm. The droplets have phase separated into Ga- and Bi-rich components. A qualitative model is proposed in which Bi is gettered into Ga droplets, leaving Bi depleted nanowires in the wakes of the droplets as they migrate in one direction across the surface during GaAs(1 x)Bi(x) film growth. PMID- 26876495 TI - With a little help from DNA barcoding: investigating the diversity of Gastropoda from the Portuguese coast. AB - The Gastropoda is one of the best studied classes of marine invertebrates. Yet, most species have been delimited based on morphology only. The application of DNA barcodes has shown to be greatly useful to help delimiting species. Therefore, sequences of the cytochrome c oxidase I gene from 108 specimens of 34 morpho species were used to investigate the molecular diversity within the gastropods from the Portuguese coast. To the above dataset, we added available COI-5P sequences of taxonomically close species, in a total of 58 morpho-species examined. There was a good match between ours and sequences from independent studies, in public repositories. We found 32 concordant (91.4%) out of the 35 Barcode Index Numbers (BINs) generated from our sequences. The application of a ranking system to the barcodes yield over 70% with top taxonomic congruence, while 14.2% of the species barcodes had insufficient data. In the majority of the cases, there was a good concordance between morphological identification and DNA barcodes. Nonetheless, the discordance between morphological and molecular data is a reminder that even the comparatively well-known European marine gastropods can benefit from being probed using the DNA barcode approach. Discordant cases should be reviewed with more integrative studies. PMID- 26876497 TI - In response: UV-vis light transmittance through tinted contact lenses and the effect of color on values. PMID- 26876496 TI - Reference frames for reaching when decoupling eye and target position in depth and direction. AB - Spatial representations in cortical areas involved in reaching movements were traditionally studied in a frontoparallel plane where the two-dimensional target location and the movement direction were the only variables to consider in neural computations. No studies so far have characterized the reference frames for reaching considering both depth and directional signals. Here we recorded from single neurons of the medial posterior parietal area V6A during a reaching task where fixation point and reaching targets were decoupled in direction and depth. We found a prevalent mixed encoding of target position, with eye-centered and spatiotopic representations differently balanced in the same neuron. Depth was stronger in defining the reference frame of eye-centered cells, while direction was stronger in defining that of spatiotopic cells. The predominant presence of various typologies of mixed encoding suggests that depth and direction signals are processed on the basis of flexible coordinate systems to ensure optimal motor response. PMID- 26876498 TI - Glaucoma surgical considerations for PROSE lens use in patients with ocular surface disease. AB - PURPOSE: To examine challenges of Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment in patients with glaucoma drainage implants (GDI) and the surgical management of patients where both GDI and PROSE treatment are indicated. METHODS: A retrospective noncomparative observational study was performed to investigate the outcomes of 7 eyes of 6 patients that required PROSE lens wear and GDI implantation. RESULTS: Group A consisted of 2 cases where PROSE lens wear was problematic due to scleral surface irregularities following GDI placement. These included changes in surface morphology caused by the elevated scleral patch graft tissue adjacent to the corneal limbus in one case and the presence of two anteriorly located shunts in the other. Group B consisted of 3 eyes where the previously placed GDI led to poor lens alignment due to the proximity of the lens edge to the scleral graft. Group C consisted of 2 cases where both patients underwent placement of the GDI in the pars plana and insertion of the drainage tube 3-3.5mm from the limbus in order to facilitate PROSE lens use. The posterior location of the tube and patch allowed for proper PROSE device alignment over the ocular surface. CONCLUSIONS: Surgical considerations and prior planning for GDI placement allows PROSE lens use for management of ocular surface disease. Pars plana tube placement with a posteriorly placed patch graft, instead of anterior chamber tube positioning with more anterior graft, enables adequate lens wear in scleral-lens-dependent patients. PMID- 26876499 TI - Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus. AB - In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood-brain barrier and tight junction markers in the rat hippocampus. Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood-brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction. PMID- 26876500 TI - Mass spectrometry analysis of the oxidation states of the pro-oncogenic protein anterior gradient-2 reveals covalent dimerization via an intermolecular disulphide bond. AB - Anterior Gradient-2 (AGR2) is a component of a pro-oncogenic signalling pathway that can promote p53 inhibition, metastatic cell migration, limb regeneration, and cancer drug-resistance. AGR2 is in the protein-disulphide isomerase superfamily containing a single cysteine (Cys-81) that forms covalent adducts with its client proteins. We have found that mutation of Cysteine-81 attenuates its biochemical activity in its sequence-specific peptide docking function, reduces binding to Reptin, and reduces its stability in cells. As such, we evaluated how chemical oxidation of its cysteine affects its biochemical properties. Recombinant AGR2 spontaneously forms covalent dimers in the absence of reductant whilst DTT promotes dimer to monomer conversion. Mutation of Cysteine-81 to alanine prevents peroxide catalysed dimerization of AGR2 in vitro, suggesting a reactive cysteine is central to covalent dimer formation. Both biochemical assays and ESI mass spectrometry were used to demonstrate that low levels of a chemical oxidant promote an intermolecular disulphide bond through formation of a labile sulfenic acid intermediate. However, higher levels of oxidant promote sulfinic or sulfonic acid formation thus preventing covalent dimerization of AGR2. These data together identify the single cysteine of AGR2 as an oxidant responsive moiety that regulates its propensity for oxidation and its monomeric-dimeric state. This has implications for redox regulation of the pro oncogenic functions of AGR2 protein in cancer cells. PMID- 26876501 TI - Clinicopathological correlates of depression in early Alzheimer's disease in the NACC. AB - OBJECTIVE: Depression may be a prodrome to Alzheimer's disease (AD). We assessed whether AD neuropathology is associated with depression in mild cognitive impairment (MCI) and mild dementia (dAD). METHODS: All clinical and neuropathological data for this study came from the National Alzheimer's Coordinating Center (NACC). Healthy control (HC, n = 120), MCI (n = 77), and mild dAD (n = 93) patients who underwent brain autopsy were included. In regression models with Geriatric Depression Scale (GDS) as the outcome, neuritic plaque (NP) score or Braak Stages of neurofibrillary (NF) pathology were covariates. RESULTS: GDS was not associated with cognitive status, NP score, Braak Stages, or their interaction. In both models, a history of TIAs, depression within the last 2 years, current benzodiazepine use, and greater severity of neuropsychiatric symptoms were associated with greater depression. In the Braak Stages model, less education was another significant predictor. CONCLUSIONS: Depression in early AD appears to be independent of NP and NF pathology. Studies are needed to investigate other mechanisms that may be responsible for depression in MCI and dAD. PMID- 26876502 TI - Graphene Oxide Attenuates the Cytotoxicity and Mutagenicity of PCB 52 via Activation of Genuine Autophagy. AB - Graphene oxide (GO), owing to its large surface area and abundance of oxygen containing functional groups, is emerging as a potential adsorbent for polychlorinated biphenyls (PCBs), which accumulate over time and are harmful to both natural ecosystems and human health. However, the effect of GO against PCB induced toxicity remains largely unexplored. The present study aimed to investigate the protective effect of GO against PCB 52 induced cytotoxic and genotoxic response in mammalian cells at various exposure conditions and clarify the protective role of autophagy. Pretreatment with GO dramatically decreased PCB 52 induced cytotoxicity and CD59 gene mutation in human-hamster hybrid (AL) cells. The toxic response in cells either pretreated with PCB 52 and then treated with GO or concurrently treated with GO and PCB 52 did not differ significantly from the toxic response in the cells treated with PCB 52 alone. Using autophagy inhibitors (3-methyladenine and wortmannin) and inducers (trehalose and rapamycin), we found that genuine autophagy induced by GO was involved in decreasing PCB 52 induced toxicity. These findings suggested that GO has an antagonistic effect against the toxicity of PCB 52 mainly by triggering a genuine autophagic process, which might provide new insights into the potential application of GO in PCB disposal and environmental and health risk assessment. PMID- 26876504 TI - An Adsorbate Discriminatory Gate Effect in a Flexible Porous Coordination Polymer for Selective Adsorption of CO2 over C2H2. AB - The adsorptive separation of C2H2 and CO2 via porous materials is nontrivial due to the close similarities of their boiling points and kinetic diameters. In this work, we describe a new flexible porous coordination polymer (PCP) [Mn(bdc)(dpe)] (H2bdc = 1,4-benzenedicarboxylic acid, dpe = 1,2-di(4-pyridyl)ethylene) having zero-dimensional pores, which shows an adsorbate discriminatory gate effect. The compound shows gate opening type abrupt adsorption for C2H2 but not for CO2, leading to an appreciable selective adsorption of CO2 over C2H2 at near ambient temperature (273 K). The origin of this unique selectivity, as unveiled by in situ adsorption-X-ray diffraction experiments and density functional theory calculations, is due to vastly different orientations between the phenylene ring of bdc and each gas in the nanopores. The structural change by photochemical transformation of this PCP via [2 + 2] photodimerization leads to the removal of inverse CO2/C2H2 selectivity, verifying the mechanism of the guest discriminatory gate effect. PMID- 26876503 TI - Efficacy of covered and bare stent in TIPS for cirrhotic portal hypertension: A single-center randomized trial. AB - We conducted a single-center randomized trial to compare the efficacy of 8 mm Fluency covered stent and bare stent in transjugular intrahepatic portosystemic shunt (TIPS) for cirrhotic portal hypertension. From January 2006 to December 2010, the covered (experimental group) or bare stent (control group) was used in 131 and 127 patients, respectively. The recurrence rates of gastrointestinal bleeding (18.3% vs. 33.9%, P = 0.004) and refractory hydrothorax/ascites (6.9% vs. 16.5%, P = 0.019) in the experimental group were significantly lower than those in the control group. The cumulative restenosis rates in 1, 2, 3, 4, and 5 years in the experimental group (6.9%, 11.5%, 19.1%, 26.0%, and 35.9%, respectively) were significantly lower (P < 0.001) than those in the control group (27.6%, 37.0%, 49.6%, 59.8%, 74.8%, respectively). Importantly, the 4 and 5 year survival rates in the experimental group (83.2% and 76.3%, respectively) were significantly higher (P = 0.001 and 0.02) than those in the control group (71.7% and 62.2%, respectively). The rate of secondary interventional therapy in the experimental group was significantly lower than that in the control group (20.6% vs. 49.6%; P < 0.001). Therefore, Fluency covered stent has advantages over the bare stent in terms of reducing the restenosis, recurrence, and secondary interventional therapy, whereas improving the long-term survival for post-TIPS patients. PMID- 26876505 TI - SCAI's future: The 2016 Strategic Plan. PMID- 26876506 TI - Restenosis after PCI: Battered but not beaten. PMID- 26876507 TI - It is not paradoxical: Risk reduction from transradial occurs across all weight classes proportional to baseline risk. PMID- 26876508 TI - Statin attenuation of stent inflammatory response. PMID- 26876509 TI - Best practices for treating coronary ostial lesions. PMID- 26876510 TI - Look left, look right, but it is mostly just straight ahead. PMID- 26876511 TI - On the search for an "easy" FFR: Submaximal hyperemia and NTG-induced translesional pressure drop (Pd/Pa-NTG). PMID- 26876512 TI - The alternative approach to transcatheter aortic valve replacement. PMID- 26876513 TI - Vascular complications in steroid treated patients undergoing trans-femoral aortic valve implantation. PMID- 26876515 TI - A facile solution-phase synthesis of cobalt phosphide nanorods/hollow nanoparticles. AB - A simple one-step solution-phase synthesis of cobalt phosphide nanorods (NRs) and hollow nanoparticles (NPs) has been reported in this paper. The phase and morphology evolutions of cobalt phosphide were researched by varying the reaction conditions. The detailed research confirms that oleylamine (OAm) in the reaction firstly reduces Co(acac)2 to the Co phase and the reaction between P atoms from TOP and Co atoms results in the Co2P phase. The as-synthesized NRs and NPs show superparamagnetic behavior at room temperature and ferromagnetic properties at 2 K. The current route provides a new and general chemical method for tunable preparation of cobalt phosphide nanostructures, which are important for further magnetic and catalytic studies. PMID- 26876514 TI - Critical assessment and ramifications of a purported marine trophic cascade. AB - When identifying potential trophic cascades, it is important to clearly establish the trophic linkages between predators and prey with respect to temporal abundance, demographics, distribution, and diet. In the northwest Atlantic Ocean, the depletion of large coastal sharks was thought to trigger a trophic cascade whereby predation release resulted in increased cownose ray abundance, which then caused increased predation on and subsequent collapse of commercial bivalve stocks. These claims were used to justify the development of a predator-control fishery for cownose rays, the "Save the Bay, Eat a Ray" fishery, to reduce predation on commercial bivalves. A reexamination of data suggests declines in large coastal sharks did not coincide with purported rapid increases in cownose ray abundance. Likewise, the increase in cownose ray abundance did not coincide with declines in commercial bivalves. The lack of temporal correlations coupled with published diet data suggest the purported trophic cascade is lacking the empirical linkages required of a trophic cascade. Furthermore, the life history parameters of cownose rays suggest they have low reproductive potential and their populations are incapable of rapid increases. Hypothesized trophic cascades should be closely scrutinized as spurious conclusions may negatively influence conservation and management decisions. PMID- 26876516 TI - Synthesis of Gold Mediated Biocompatible Nanocomposite of Lactone Enriched Fraction from Sahadevi (Vernonia cinerea Lees): An Assessment of Antimalarial Potential. AB - Metals reduction into submicro/nano size through bhasma preparations for therapeutic use is well established in ancient traditional system of Indian medicines i.e. Ayurveda. Recently, nanotechnology has drawn the attention of researchers to develeope various size and shape nanoparicles / composite for number of applications.In this article, we report the enrichment of lactone enriched fraction (LEF) by liquid-liquid portioning of Vernonia cinerea metabolic extract and sysnthesis of mediated nano-gold composite (LEF-AuNPs) in single step process. The morphological characteristic based on transmission electron microscope (TEM) image analysis showed that LEF-AuNPs were predominantly nanopolygons and nanobots in shapes ranging from 50-200 nm in size. Abundance of phytochemicals in both LEF and LEF-AuNPs was dissimilar. In LEF, montanol- a diterpenoid, while in LEF-AuNPs, neophytadiene- a phytanes was the major compound. HPLC profile of relatively polar compounds also varied drastically. In vitro biocompatibility, cytotoxicity [MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) based assay] and storage stabilitiy of LEF-AuNPs were evaluated. The moderate ability of LEF-AuNPs to restrict parasitaemia, extended mean survival time of mice infected with Plasmodium berghei and lack of any evident toxicity provides new opportunities for the safe delivery and applications of such nanocomposites in malaria therapy. PMID- 26876517 TI - Development of Quercetin Based Nanodispersions. AB - Polyphenols are a large group of structurally diverse natural products, including flavonoids. One of the most bioactive compounds of this class is the flavonol quercetin, a recognized antioxidant. Despite several studies were carried out aiming to develop nanoformulations with secondary metabolites, to our knowledge, quercetin was not used as raw material for nanodispersion production without coating polymers. This type of nanosize formulation is often prepared using organic solvents and quercetin nanodispersions were prepared by emulsification evaporation technique, using 1(6).2(2) experimental factorial design, ("surfactant type" evaluated at 6 levels, "surfactant amount" and "stirring speed" evaluated at 2 levels). Variance analysis, after one day of nanodispersions preparation, revealed that only the surfactant type was statistically significant on particle size, while none of factors presented statistically significant effect on polydispersity index. Variance analysis after seven days of nanodispersions preparation revealed that either surfactant type and surfactant amount presented significant effect on particle size, while only surfactant type influenced polydispersity index. Some nanodispersions presented small diameter and narrow size distribution, suggesting potential stability of these systems. Special attention was given to nanodispersion prepared with 3 % (w/w) of polyethylene glycol 400 monooleate (expressed as function of surfactant concentration at aqueous phase). It presented mean droplet size of 129.4 +/- 0.5 nm and polydispersity index of 0.173 +/- 0.018, after 7 days of preparation. Low polydispersity index indicates a high homogeneity concerning particle size distribution and suggests stability of the system. Moreover, absence of coating polymers and utilization of a low energy method would be an advantage in terms of reducing costs for industrial application, without any nanosize impairment. PMID- 26876518 TI - Development and Characterization of Cassia grandis and Bixa orellana Nanoformulations. AB - Cassia grandis and Bixa orellana are important plant species with folk use and great potential for phytopharmaceuticals. Nanodispersions are disperse systems of insoluble or immiscible substances in a liquid medium that may be prepared with or without coating polymers. To our knowledge, no studies were carried in order to achieve coating-polymer free nanoformulations using B. orellana extract or any C. grandis-based nanoformulations. Thus, on the present study we aimed to develop C. grandis nanoformulations using three different coating polymers (Eudragit(r) L 100 55, PEG 4000 and Kollicoat(r)), while B. orellana nanodispersions were obtained using different surfactants (polysorbate 80, polysorbate 20, polyethylene glycol 400 monooleate, polyethylene glycol 600 monooleate, polyethylene glycol 400 dioleate and polyethylene glycol 600 dioleate) as coating polymer-free nanoformulations. Characterization of nanoformulations was performed by different parameters, including particle size, polydispersity index and zeta potential. Our results suggested that some optimal nanoformulations were obtained for both plant species. Moreover, possible stable behavior was observed during storage period for C. grandis (30 days) and B. orellana (21 days). On this context, the present study contributes to nanobiotechnology development of phytopharmaceuticals, allowing achievement of novel nano-delivery systems with two important folk medicinal plant extracts and making them potential products for innovative phytopharmaceuticals. PMID- 26876519 TI - Biosynthesis of Anti-Proliferative Gold Nanoparticles Using Endophytic Fusarium oxysporum Strain Isolated from Neem (A. indica) Leaves. AB - Here we report a simple, rapid, environment friendly approach for the synthesis of gold nanoparticles using neem (Azadirachta indica A. Juss.) fungal endophyte, which based upon morphological and cultural characteristics was eventually identified as Fusarium oxysporum. The aqueous precursor (HAuCl4) solution when reacted with endophytic fungus resulted in the biosynthesis of abundant amounts of well dispersed gold nanoparticles of 10-40 nm with an average size of 22nm. These biosynthesized gold nanoparticles were then characterized by standard analytical techniques such as UV-Visible spectroscopy, X-ray diffraction, Transmission Electron Microscopy and Fourier Transform Infrared Spectroscopy. Cytotoxic activity of these nanoparticles was checked against three different cell types including breast cancer (ZR-75-1), Daudi (Human Burkitt's lymphoma cancer) and normal human peripheral blood mononuclear cells (PBMC), where it was found that our gold nanoparticles are anti-proliferative against cancer cells but completely safe toward normal cells. In addition to this, assessment of toxicity toward human RBC revealed less than 0.1 % hemolysis as compared to Triton X-100 suggesting safe nature of our biosynthesized gold nanoparticles on human cells. Also, our nanoparticles exhibited no anti-fungal (against Aspergillus niger) or anti-bacterial [against Gram positive (Bacillus subtilis & Staphylococcus aureus) and Gram negative (Escherichia coli & Pseudomonas aeruginosa) bacteria] activity thus suggesting their non-toxic, biocompatible nature. The present investigation opens up avenues for ecofriendly, biocompatible nanomaterials to be used in a wide variety of application such as drug delivery, therapeutics, theranostics and so on. PMID- 26876520 TI - Development of Crystalline Cellulosic Fibres for Sustained Release of Drug. AB - Natural quinoline alkaloid camptothecin (CPT) is used for the treatment of colon, lung, breast and ovarian cancers still facing challenges due to low solubility in aqueous and biological fluids. Its lactone form easily converts into a toxic carboxylic form at slightly basic pH, typical in blood and tissue fluid has rapid clearance from systemic administration. We report a new approach based on micro crystalline cellulose (MCC) and nano crystalline cellulose (NCC) isolated from natural sources such as Cymbopogan flexuosus to stabilize and regulate the release kinetics of CPT in physiological solution. Langmuir and Freundlich isotherm studies approve that degree of crystallinity i.e. ratio of amorphous and crystalline cellulose regulate the adsorption of CPT. The freeze dried celluloses of Cymbopogan flexuosus origin (MCC and NCC) further were optimized for drug delivery with a mimicked physiologically relevant solution. Both carriers can significantly extend the release of drug as compared to reported values, however, NCC showed better results. Not only the crystallinity but crystal size and hydrogen bonding play critical role in drug release. Free diffusion of drug into physiological solution follows the Ritger- Peppes kinetic model. The coefficient of the model signifies the Fickian diffusion mechanism of release. The investigation indicates that NCC cellulosic matrix can act as a better carrier of CPT for its sustained release formulation. PMID- 26876521 TI - Biosynthesis of Fluorescent Bi2S3 Nanoparticles and their Application as Dual Function SPECT-CT Probe for Animal Imaging. AB - Bismuth sulphide (Bi2S3) is an excellent semiconductor and its nanoparticles have numerous significant applications including photovoltaic materials, photodiode arrays, bio-imaging, etc. Nevertheless, these nanoparticles when fabricated by chemical and physical routes tend to easily aggregate in colloidal solutions, are eco-unfriendly, cumbrous and very broad in size distribution. The aim of the present manuscript was to ecologically fabricate water dispersible, safe and stable Bi2S3 nanoparticles such that these may find use in animal imaging, diagnostics, cell labeling and other biomedical applications. Herein, we for the first time have biosynthesized highly fluorescent, natural protein capped Bi2S3 nanoparticles by subjecting the fungus Fusarium oxysporum to bismuth nitrate pentahydrate [Bi(NO3)3.5H2O] alongwith sodium sulphite (Na2SO3) as precursor salts under ambient conditions of temperature, pressure and pH. The nanoparticles were completely characterized using recognized standard techniques. These natural protein capped Bi2S3 nanoparticles are quasi-spherical in shape with an average particle size of 15 nm, maintain long term stability and show semiconductor behavior having blue shift with a band gap of 3.04 eV. Semiconductor nanocrystals are fundamentally much more fluorescent than the toxic fluorescent chemical compounds (fluorophores) which are presently largely employed in imaging, immunohistochemistry, biochemistry, etc. Biologically fabricated fluorescent nanoparticles may replace organic fluorophores and aid in rapid development of biomedical nanotechnology. Thus, biodistribution study of the so-formed Bi2S3 nanoparticles in male Sprague Dawley rats was done by radiolabelling with Technitium-99m (Tc-99m) and clearance time from blood was calculated. The nanoparticles were then employed in SPECT-CT probe for animal imaging where these imparted iodine equivalent contrast. PMID- 26876523 TI - Advancements in Devices and Particle Engineering in Dry Powder Inhalation Technology. AB - Dry powder inhalers (DPI) attracted the attention of pharmaceutical field due to its enlarging market share in inhalable formulations. These formulations also pose patient compliance and good shelf life. Earlier DPI formulations were intended for local effect in lung (asthma and chronic obstructive pulmonary diseases), whereas 21(st) century witnessed formulations intended for systemic effect too. A better understanding of physiology of lung and fluidics of air flow helped in targeting alveoli using DPI technology. Modern characterization tools also accelerated the research pace. In addition to the synthetic molecules, DPI also was proved to be a better system for delivering biological molecules including vaccines. This review includes the mechanisms of drug deposition, advancements in the fields of DPI devices, various characterization tools and particle engineering. In this review we have related the chronological advancement of inhalational technology starting from 1788 AD to the present. PMID- 26876522 TI - The Unexpected Advantages of Using D-Amino Acids for Peptide Self- Assembly into Nanostructured Hydrogels for Medicine. AB - Self-assembled peptide hydrogels have brought innovation to the medicinal field, not only as responsive biomaterials but also as nanostructured therapeutic agents or as smart drug delivery systems. D-amino acids are typically introduced to increase the peptide enzymatic stability. However, there are several reports of unexpected effects on peptide conformation, self-assembly behavior, cytotoxicity and even therapeutic activity. This mini-review discusses all the surprising twists of heterochiral self-assembled peptide hydrogels, and delineates emerging key findings to exploit all the benefits of D-amino acids in this novel medicinal area. PMID- 26876524 TI - The Glitter of Carbon Nanostructures in Hybrid/Composite Hydrogels for Medicinal Use. AB - In recent years, we have witnessed to fast developments in the medicinal field of hydrogels containing various forms of integrated nanostructured carbon that adds interesting mechanical, thermal, and electronic properties. Besides key advances in tissue engineering (especially for conductive tissue, such as for the brain and the heart), there has been innovation also in the area of drug delivery on demand, with engineered hydrogels capable of repeated response to light, thermal, or electric stimuli. This mini-review focusses on the most promising developments as applied to the gelation of protein/ peptide (including self-assembling amino acids and low-molecular-weight gelators), polysaccharide, and/or synthetic polymer components in medicine. The emerging field of graphene-only hydrogels is also briefly discussed, to give the reader a full flavor of the rising new paradigms in medicine that are made possible through the integration of nanostructured carbon (e.g., carbon nanotubes, nanohorns, nanodiamonds, fullerene, etc.). Nanocarbons are offering great opportunities to bring on a revolution in therapy that the modern medicinal chemist needs to master, to realise their full potential into powerful therapeutic solutions for the patient. PMID- 26876525 TI - Nano Particles: Emerging Warheads Against Bacterial Superbugs. AB - Infectious diseases are one of the major causes of morbidity and mortality in children in developing and underdeveloped countries. Limited knowledge of targets (cell wall synthesis, replication, transcription, protein synthesis) for antibiotics and lack of novel antibiotics have lead to an emergence of different level of resistance in bacterial pathogens. Multidrug resistance is the phenomenon by which the bacteria exerts resistance against the two or more structurally unrelated drugs/antibiotics. A common goal in the post-genomic era is to identify novel targets/drugs for various life threatening bacterial pathogens. Nanoparticles are broadly defined as submicron colloidal particles of size less than 1MUm. Nanoparticles of size less than 100nm are the most promising warheads to overcome microbial drug resistance because they can act as antibacterial/antibiotic modulating agents at the site of infection and may have more than one mode of action. These nanoparticles will be of immense help in transporting drugs directly at the infected sites. Thus prevent drug resistance development to a great extent. In this review, the key mechanisms of resistance in bacterial superbugs have been discussed as well as how nanoparticles can overcome them. It is hypothesized that the nanoparticles can overcome the drug resistance via a novel mechanism of action. Additionaly, nanopaticles may also work synergistically with antibiotics via increased uptake, decreased efflux and inhibition of biofilm formation. The degradation by metallo beta lactamases and synthesis of porins may also be facilitated through these nanoparticles. PMID- 26876528 TI - Nanoarchitectonics for carbon-material-based sensors. AB - Recently, the nanoarchitectonics concept has been proposed to fabricate functional materials on the basis of concerted harmonization actions to control materials organization. In this review, we introduce recent several sensor designs from viewpoints of nanoarchitectonics that are classified into three categories: (i) inside nanoarchitectonics, (ii) outside nanoarchitectonics, and (iii) hierarchic nanoarchitectonics. In addition, various nanocarbons, such as carbon nanotubes, graphene derivatives, fullerene assemblies and nanoporous carbons, are selected as standard materials. In the first section, design and fabrication of mesoporous or nanoporous materials for enhanced sensing are especially exemplified as inside nanoarchitectonics. In the next section, recent examples of layer-by-layer nanoarchitectures for sensor fabrications are explained for outside nanoarchitectonics. Finally, their combined strategies for hierarchic carbon nanoarchitectonics are introduced as advanced sensor materials designs. PMID- 26876526 TI - Insulin and IGF-1 regularize energy metabolites in neural cells expressing full length mutant huntingtin. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder linked to the expression of mutant huntingtin. Bioenergetic dysfunction has been described to contribute to HD pathogenesis. Thus, treatment paradigms aimed to ameliorate energy deficits appear to be suitable candidates in HD. In previous studies, we observed protective effects of insulin growth factor-1 (IGF-1) in YAC128 and R6/2 mice, two HD mouse models, whereas IGF-1 and/or insulin halted mitochondrial-driven oxidative stress in mutant striatal cells and mitochondrial dysfunction in HD human lymphoblasts. Here, we analyzed the effect of IGF-1 versus insulin on energy metabolic parameters using striatal cells derived from HD knock-in mice and primary cortical cultures from YAC128 mice. STHdh(Q111/Q111) cells exhibited decreased ATP/ADP ratio and increased phosphocreatine levels. Moreover, pyruvate levels were increased in mutant cells, most probably in consequence of a decrease in pyruvate dehydrogenase (PDH) protein expression and increased PDH phosphorylation, reflecting its inactivation. Insulin and IGF-1 treatment significantly decreased phosphocreatine levels, whereas IGF-1 only decreased pyruvate levels in mutant cells. In a different scenario, primary cortical cultures derived from YAC128 mice also displayed energetic abnormalities. We observed a decrease in both ATP/ADP and phosphocreatine levels, which were prevented following exposure to insulin or IGF-1. Furthermore, decreased lactate levels in YAC128 cultures occurred concomitantly with a decline in lactate dehydrogenase activity, which was ameliorated with both insulin and IGF-1. These data demonstrate differential HD-associated metabolic dysfunction in striatal cell lines and primary cortical cultures, both of which being alleviated by insulin and IGF-1. PMID- 26876527 TI - Effects of Task-Oriented Training as an Added Treatment to Electromyogram Triggered Neuromuscular Stimulation on Upper Extremity Function in Chronic Stroke Patients. AB - The purpose of the present study was to investigate the effects of electromyogram triggered neuromuscular stimulation (EMG-stim) combined with task-oriented training (TOT) on upper extremity function in chronic stroke patients. Twenty chronic stroke patients were randomly assigned to either the intervention (n = 10) or control (n = 10) group. The intervention group conducted TOT with EMG-stim on the wrist and finger extensor of the affected arm for 30 minutes per day, 5 days per week, for 4 weeks. The control group was provided EMG-stim for 20 minutes per day for the same duration. The intervention group exhibited significant improvement relative to the control group in muscle activation, motor recovery (Fugl-Meyer assessment) and dexterity (Box and Block Test) (p < 0.05). Significant differences in hand function between the groups were detected in the writing of short sentences and in stacking checkers (p < 0.05). It is concluded that EMG-stim in combination with TOT may be better than EMG-stim alone for the treatment of arm paresis in stroke patients. Further research with a larger sample is recommended to examine neurologic changes or cerebral cortex reorganization. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876529 TI - An insight to the role of Cr in the process of intrinsic point defects in alpha Al2O3. AB - Cr is a commonly existing impurity in alpha-Al2O3, and thus the role of Cr in the process of intrinsic point defects in alpha-Al2O3 has been studied based on first principle calculations. The results show that Cr has significant influence on the formation, charge state, relative stability and equilibrium configuration of isolated intrinsic point defects in alpha-Al2O3, resulting in the variation of defect process. Specifically, depending on the O-condition, the possible defect types, the dominant defects and the defect formation energies will be altered in alpha-Al2O3 after Cr doping. Generally speaking, Cr is favorable for the formation of Schottky defects, Frenkel defects and antisite pairs, giving a different insight to the defect process in alpha-Al2O3. PMID- 26876530 TI - 3D Printed models of distal radius fractures. PMID- 26876531 TI - Validation of methodology for assessment of pulmonary function in patients who undergo total laryngectomy. AB - BACKGROUND: In patients submitted to laryngectomy, pulmonary complications may lead to death. A simple method with a standardized extratracheal device for the pulmonary assessment of laryngectomized patients would be very useful. The purpose of this study was to validate the methodology for pulmonary assessment in these patients through the application of an adhesive extratracheal device. METHODS: This transversal study included 50 patients who had been submitted to total laryngectomy. Pulmonary tests were used to characterize the presence of respiratory functional limitation. Aiming at evaluating the reproducibility of the performed tests, parameters were used for the acceptance of the tests. A comparison of these parameters was made with 50 tests performed in nonlaryngectomized patients. RESULTS: The total of rejected tests was greater in the control group when compared to the laryngectomized group. CONCLUSION: The methodology for the assessment of the pulmonary function by using the extratracheal proposed device is reliable, accurate, and reproducible. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2030-E2034, 2016. PMID- 26876532 TI - EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms. AB - Several studies reported somatic mutations of many genes (MEN1, CTNNB1, CDKIs and others) in parathyroid adenoma, although with different prevalence. Recently, activating mutations of the EZH2 and ZFX oncogenes were identified in benign parathyroid adenoma by whole exome sequencing. The same mutations had been found in blood and ovary malignant tumours. On one hand, this result raised the hypothesis that these oncogenes may play a role in the onset of parathyroid tumour, but it would also suggest they may be involved in malignant, rather benign, parathyroid neoplasm. Our aim was to verify the occurrence of selected mutations of the EZH2 and ZFX genes in an Italian cohort of 23 sporadic parathyroid carcinomas, 12 atypical and 45 typical adenomas. DNA was extracted from paraffin-embedded tissues, PCR amplified and directly sequenced. No mutations were detected in the coding sequence and boundaries of both genes in any of the samples. Two polymorphisms of the EZH2 gene were identified with different prevalence: the rs2072407 variant was present in the 30 % of the samples, in keeping with the overall frequency in larger populations, while the rs78589034 variant, located close to the 5' end of the exon 16, was detected in only one proband with familial isolated hyperparathyroidism; we investigated the possible outcome on the splicing process. EZH2 and ZFX genes do not seem to have an impact on the onset of most parathyroid tumours, both benign and malignant, though further studies on larger cohorts of different ethnicity are needed. PMID- 26876533 TI - Maternal sleep deprivation at different stages of pregnancy impairs the emotional and cognitive functions, and suppresses hippocampal long-term potentiation in the offspring rats. AB - BACKGROUND: Sleep deprivation during pregnancy is a serious public health problem as it can affect the health of pregnant women and newborns. However, it is not well studied whether sleep deprivation at different stages of pregnancy has similar effects on emotional and cognitive functions of the offspring, and if so, the potential cellular mechanisms also remain poorly understood. METHODS: In the present study, the pregnant rats were subjected to sleep deprivation for 6 h per day by gentle handling during the first (gestational days 1-7), second (gestational days 8-14) and third trimester (gestational days 15-21) of pregnancy, respectively. The emotional and cognitive functions as well as hippocampal long-term potentiation (LTP) were tested in the offspring rats (postnatal days 42-56). RESULTS: The offspring displayed impaired hippocampal dependent spatial learning and memory, and increased depressive- and anxiety-like behaviors. Quantification of BrdU-positive cells revealed that adult hippocampal neurogenesis was significantly reduced compared to control. Electrophysiological recording showed that maternal sleep deprivation impaired hippocampal CA1 LTP and reduced basal synaptic transmission, as reflected by a decrease in the frequency and amplitude of miniature excitatory postsynaptic current in the hippocampal CA1 pyramidal neurons. CONCLUSIONS: Taken together, these results suggest that maternal sleep deprivation at different stages of pregnancy disrupts the emotional and cognitive functions of the offspring that might be attributable to the suppression of hippocampal LTP and basal synaptic transmission. PMID- 26876534 TI - Transgenerational Transmission of the Effect of Gestational Ethanol Exposure on Ethanol Use-Related Behavior. AB - BACKGROUND: Prenatal alcohol exposure (PAE) enhances the risk for alcoholism by increasing the propensity to consume alcohol and altering neurophysiological response to alcohol challenge. Trans-generationally transmittable genetic alterations have been implicated in these behavioral changes. To date, transgenerational transmission of PAE-induced behavioral responses to alcohol has never been experimentally investigated. Therefore, we explored the transgenerational transmission of PAE-induced behavioral effects across 3 generations. METHODS: Pregnant Sprague Dawley dams received 1 g/kg ethanol (EtOH) or water daily on gestational days 17 through 20 via gavage, or remained untreated in their home cages. To produce second filial (F2) or F3 generations, similarly treated adult F1 or F2 offspring were mated and left undisturbed through gestation. On postnatal day (PND) 14, male and female F1, F2, and F3 offspring were tested for consumption of 5% (w/v) EtOH (in water), or water. Using the loss of righting reflex (LORR) paradigm on PND 42, F1 and F2 adolescent male offspring were tested for sensitivity to acute EtOH-induced sedation hypnosis at 3.5 or 4.5 g/kg dose. F3 male adolescents were similarly tested at 3.5 g/kg dose. Blood EtOH concentration (BEC) was measured at waking. RESULTS: EtOH exposure increased EtOH consumption compared to both water and untreated control groups in all generations. EtOH-treated group F1 and F2 adolescents displayed attenuated LORR duration compared to the water group. No attenuated LORR was observed in the F3 generation. BEC at waking corroborated with the significant LORR duration differences while also revealing differences between untreated control and water groups in F1 and F2 generations. CONCLUSIONS: Our results provide novel behavioral evidence attesting that late gestational moderate EtOH exposure increases EtOH intake across 3 generations and may alter sensitivity to EtOH-induced sedation-hypnosis across 2 generations. PMID- 26876535 TI - The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis. AB - As a broad-spectrum anti-microbial peptide, LL-37 plays an important role in the innate immune system. A series of previous reports implicates LL-37 as an activator of various cell surface receptor-mediated functions, including chemotaxis in integrin CD11b/CD18 (Mac-1)-expressing cells. However, evidence is scarce concerning the direct binding of LL-37 to these receptors and investigations on the associated binding kinetics is lacking. Mac-1, a member of the beta2 integrin family, is mainly expressed in myeloid leukocytes. Its critical functions include phagocytosis of complement-opsonized pathogens. Here, we report on interactions of LL-37 and its fragment FK-13 with the ligand-binding domain of Mac-1, the alpha-chain I domain. LL-37 bound the I-domain with an affinity comparable to the complement fragment C3d, one of the strongest known ligands for Mac-1. In cell adhesion assays both LL-37 and FK-13 supported binding by Mac-1 expressing cells, however, with LL-37-coupled surfaces supporting stronger cell adhesion than FK-13. Likewise, in phagocytosis assays with primary human monocytes both LL-37 and FK-13 enhanced uptake of particles coupled with these ligands but with a tendency towards a stronger uptake by LL-37. PMID- 26876536 TI - The molecular mechanism of heme loss from oxidized soluble guanylate cyclase induced by conformational change. AB - Heme oxidation and loss of soluble guanylate cyclase (sGC) is thought to be an important contributor to the development of cardiovascular diseases. Nevertheless, it remains unknown why the heme loses readily in oxidized sGC. In the current study, the conformational change of sGC upon heme oxidation by ODQ was studied based on the fluorescence resonance energy transfer (FRET) between the heme and a fluorophore fluorescein arsenical helix binder (FlAsH-EDT2) labeled at different domains of sGC beta1. This study provides an opportunity to monitor the domain movement of sGC relative to the heme. The results indicated that heme oxidation by ODQ in truncated sCC induced the heme-associated alphaF helix moving away from the heme, the Per/Arnt/Sim domain (PAS) domain moving closer to the heme, but led the helical domain going further from the heme. We proposed that the synergistic effect of these conformational changes of the discrete region upon heme oxidation forces the heme pocket open, and subsequent heme loss readily. Furthermore, the kinetic studies suggested that the heme oxidation was a fast process and the conformational change was a relatively slow process. The kinetics of heme loss from oxidized sGC was monitored by a new method based on the heme group de-quenching the fluorescence of FlAsH-EDT2. PMID- 26876537 TI - Seed thioredoxin h. AB - Thioredoxins are nearly ubiquitous disulfide reductases involved in a wide range of biochemical pathways in various biological systems, and also implicated in numerous biotechnological applications. Plants uniquely synthesize an array of thioredoxins targeted to different cell compartments, for example chloroplastic f and m-type thioredoxins involved in regulation of the Calvin-Benson cycle. The cytosolic h-type thioredoxins act as key regulators of seed germination and are recycled by NADPH-dependent thioredoxin reductase. The present review on thioredoxin h systems in plant seeds focuses on occurrence, reaction mechanisms, specificity, target protein identification, three-dimensional structure and various applications. The aim is to provide a general background as well as an update covering the most recent findings. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID- 26876538 TI - Surgical outcome and patterns of recurrence for retroperitoneal sarcoma at a single centre. AB - INTRODUCTION: Retroperitoneal sarcoma is a surgically managed condition that can recur locally following macroscopically complete resection. Owing to the low incidence of the condition, advances in treatment are reported infrequently but complete compartmental resection and adjuvant or neoadjuvant radiotherapy are areas under investigation. Given the practical difficulty of randomised trials, observational data can highlight advantages from progressive treatment approaches. METHODS: A retrospective database of consecutive retroperitoneal sarcoma resections performed at a single referral centre between March 1997 and March 2013 was interrogated. Histological, radiological and clinical data were collected. Univariate and multivariate analyses for disease free and overall survival were performed to establish independent predictors of disease recurrence and patient survival. RESULTS: A total of 79 patients underwent 90 resections (63 primary). The mean five-year overall and disease free survival rates were 55.3% and 24.8% respectively. Higher patient age, high tumour grade, presence of extraretroperitoneal disease and invasive tumour phenotype were found to significantly predict survival following multivariate analysis. Half (50%) of the tumours displayed invasive behaviour on histopathology and 42% of locoregional recurrence was intraperitoneal. CONCLUSIONS: Retroperitoneal sarcoma is commonly an infiltrative tumour and often recurs outside of the retroperitoneum. These features limit the therapeutic impact of interventions that focus on gaining local control such as complete compartmental resection and radiotherapy. It seems likely that future advances in the management of this cancer will involve new systemic agents to treat this frequently systemic disease. PMID- 26876539 TI - Detection of cross-sex chimerism in the common marmoset monkey (Callithrix jacchus) in interphase cells using fluorescence in situ hybridisation probes specific for the marmoset X and Y chromosomes. AB - Chimerism associated with placental sharing in marmosets has been traditionally analysed using conventional chromosome staining on metaphase spreads or polymerase chain reaction. However, the former technique requires the presence of proliferating cells, whereas the latter may be associated with possible blood cell contamination. Therefore, we aimed to develop a single-cell analysis technique for sexing marmoset cells. We applied fluorescent in situ hybridisation (FISH) to cell nuclei using differentially labelled X and Y chromosome-specific probes. Herein we present the validation of this method in metaphase cells from a marmoset lymphoblastoid cell line, as well as application of the method for evaluation of cross-sex chimerism in interphase blood lymphocytes and haematopoietic bone marrow cells from marmosets of same- and mixed-sex litters. The results show conclusively that haematopoietic cells of bone marrow and leucocytes from blood are cross-sex chimeric when the litter is mixed sex. In addition, single samples of liver and spleen cell suspensions from one individual were tested. Cross-sex chimerism was observed in the spleen but not in liver cells. We conclude that FISH is the method of choice to identify cross-sex chimerism, especially when combined with morphological identification of nuclei of different cell types, which will allow a targeted tissue-specific analysis. PMID- 26876557 TI - Photodegradation of PAHs in passive water samplers. AB - Losses of deuterated polycyclic aromatic hydrocarbons (PAHs) used as performance reference compounds (PRCs) in semipermeable membrane devices deployed at fifteen coastal sampling sites near Harstad harbour in Northern Norway were used to investigate photodegradation of these photosensitive compounds. Unusual PRC dissipation profiles, especially for samplers exposed <5m below the water surface are indicative of photodegradation. A strong correlation between loss rates for d12-chrysene and d12-benzo[e]pyrene with consistently higher losses of the latter was found. The observed photodegradation rates may be sufficiently high to impact PAH masses absorbed by a factor of two. This study demonstrates that photodegradation during exposure of passive water samplers needs to be taken into account, particularly with deployments close to the water surface, when using SPMD canisters, or when sampling in the Arctic. PMID- 26876558 TI - Water quality dynamics in an urbanizing subtropical estuary(Oso Bay, Texas). AB - Results are presented from a study of water quality dynamics in a shallow subtropical estuary, Oso Bay, Texas, which has a watershed that has undergone extensive urbanization in recent decades. High inorganic nutrient, dissolved organic matter and chlorophyll concentrations, as well as low pH (<8), were observed in a region of Oso Bay that receives wastewater effluent. Despite being shallow (<1 m) and subjected to strong winds on a regular basis, this region also exhibited episodic hypoxia/anoxia. The low oxygen and pH conditions are likely to impose significant stress on benthic organisms and nekton in the affected area. Signatures of eutrophied water were occasionally observed at the mouth of Oso Bay, suggesting that it may be exported to adjacent Corpus Christi Bay and contribute to seasonal hypoxia development in that system as well. These results argue for wastewater nutrient input reductions in order to alleviate the symptoms of eutrophication. PMID- 26876559 TI - Comparison of heavy metal contamination during the last decade along the coastal sediment of Pakistan: Multiple pollution indices approach. AB - Heavy metals concentrations (Fe, Cu, Zn, Ni, Cr, Co, Pb, and Cd) were scrutinized during two monitoring years (2001 and 2011) in the coastal sediment of Pakistan. The status of metal contamination in coastal sediment was interpreted using sediment quality guidelines, and single and combined metal pollution indices. Ni, Cr, and Cd were recognized for their significant (p<0.05) intensification in the sediment during the last decade. Sediment quality guidelines recognized the frequent adverse biological effect of Ni and the occasional adverse biological effect of Cu, Cr, Pb and Cd. Single metal pollution indices (Igeo, EF, CF, and ER) revealed that sediment pollution is predominantly caused by Pb and Cd. Low to moderate contamination was appraised along the coast by multi-metal pollution indices (CD and PERI). Correlation study specifies that heavy metals were presented diverse affiliations and carriers for distribution in the sediment during the last decade. PMID- 26876560 TI - Multidrug-resistant Vibrio associated with an estuary affected by shrimp farming in Northeastern Brazil. AB - Bacteria of genus Vibrio with multidrug resistance in shrimp farm environment were recurrent. Thus, the aim of this study was to evaluate the antimicrobial resistance profile of 70 strains of Vibrio isolated from water and sediment of Acarau estuary, Ceara, Brazil. In order to achieve this goal, disk diffusion technique was used with the following antimicrobial agents: ampicillin (Amp), aztreonam (Atm), cephalothin (Cef), cefotaxime (Ctx), ceftriaxone (Cro), ciprofloxacin (Cip), chloramphenicol (Clo), florfenicol (Flo), nitrofurantoin (Nit), gentamicin (Gen), oxytetracycline (Otc), tetracycline (Tet), streptomycin (Str), nalidixic acid (Nal), and sulfazotrim (Sut). All Vibrio strains were resistant to at least one antimicrobial agent, being verified as 17 multidrug resistant profiles. All strains resistant to Otc and Tet were characterized to exhibit plasmidial resistance. Therefore, Vibrio strains from Acarau estuary pose a risk to public health and aquatic culture. PMID- 26876561 TI - Liraglutide Compromises Pancreatic beta Cell Function in a Humanized Mouse Model. AB - Incretin mimetics are frequently used in the treatment of type 2 diabetes because they potentiate beta cell response to glucose. Clinical evidence showing short term benefits of such therapeutics (e.g., liraglutide) is abundant; however, there have been several recent reports of unexpected complications in association with incretin mimetic therapy. Importantly, clinical evidence on the potential effects of such agents on the beta cell and islet function during long-term, multiyear use remains lacking. We now show that prolonged daily liraglutide treatment of >200 days in humanized mice, transplanted with human pancreatic islets in the anterior chamber of the eye, is associated with compromised release of human insulin and deranged overall glucose homeostasis. These findings raise concern about the chronic potentiation of beta cell function through incretin mimetic therapy in diabetes. PMID- 26876563 TI - Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution - a potential target for anti-tuberculosis drug discovery. AB - The biosynthetic pathway for the branched-chain amino acids is present in plants, fungi and bacteria, but not in animals, making it an attractive target for herbicidal and antimicrobial drug discovery. Ketol-acid reductoisomerase (KARI; EC 1.1.1.86) is the second enzyme in this pathway, converting in a Mg(2+) - and NADPH-dependent reaction either 2-acetolactate or 2-aceto-2-hydroxybutyrate to their corresponding 2,3-dihydroxy-3-alkylbutyrate products. Here, we have determined the crystal structure of Mycobacterium tuberculosis (Mt) KARI, a class I KARI, with two magnesium ions bound in the active site. X-ray data were obtained to 1.0 A resolution and the final model has an Rfree of 0.163. The structure shows that the active site is solvent-accessible with the two metal ions separated by 4.7 A. A comparison of this structure with that of Mg(2+) -free Pseudomonas aeruginosa KARI suggests that upon magnesium binding no movement of the N domain relative to the C domain occurs. However, upon formation of the Michaelis complex, as illustrated in the structure of Slackia exigua KARI in complex with NADH.Mg(2+) . N-hydroxy-N-isopropyloxamate (IpOHA, a transition state analog), domain movements and reduction of the metal-metal distance to 3.5 A are observed. This inherent flexibility therefore appears to be critical for initiation of the KARI-catalyzed reaction. This study provides new insights into the complex structural rearrangements required for activity of KARIs, particularly those belonging to class I, and provides the framework for the rational design of Mt KARI inhibitors that can be tested as novel antituberculosis agents. DATABASE: Coordinates and structure factors for the Mt KARI.Mg(2+) complex are available in the Protein Data Bank under accession number 4YPO. PMID- 26876562 TI - A Secreted Slit2 Fragment Regulates Adipose Tissue Thermogenesis and Metabolic Function. AB - Activation of brown and beige fat can reduce obesity and improve glucose homeostasis through nonshivering thermogenesis. Whether brown or beige fat also secretes paracrine or endocrine factors to promote and amplify adaptive thermogenesis is not fully explored. Here we identify Slit2, a 180 kDa member of the Slit extracellular protein family, as a PRDM16-regulated secreted factor from beige fat cells. In isolated cells and in mice, full-length Slit2 is cleaved to generate several smaller fragments, and we identify an active thermogenic moiety as the C-terminal fragment. This Slit2-C fragment of 50 kDa promotes adipose thermogenesis, augments energy expenditure, and improves glucose homeostasis in vivo. Mechanistically, Slit2 induces a robust activation of PKA signaling, which is required for its prothermogenic activity. Our findings establish a previously unknown peripheral role for Slit2 as a beige fat secreted factor that has therapeutic potential for the treatment of obesity and related metabolic disorders. PMID- 26876564 TI - One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease. AB - BACKGROUND: Refractory tremor in tremor-dominant (TD) or equivalent-type (EQT) idiopathic Parkinson's syndrome (IPS) poses the challenge of choosing the best target region to for deep brain stimulation (DBS). While the subthalamic nucleus is typically chosen in younger patients as the target for dopamine-responsive motor symptoms, it is more complicated if tremor does not (fully) respond under trial conditions. In this report, we present the first results from simultaneous bilateral DBS of the DRT (dentato-rubro-thalamic tract) and the subthalamic nucleus (STN) in two elderly patients with EQT and TD IPS and dopamine-refractory tremor. METHODS: Two patients received bilateral octopolar DBS electrodes in the STN additionally traversing the DRT region. Achieved electrode positions were determined with helical CT, overlaid onto DTI tractography data, and compared with clinical data of stimulation response. RESULTS: Both patients showed immediate and sustained improvement of their tremor, bilaterally. CONCLUSIONS: The proposed approach appears to be safe and feasible and a combined stimulation of the two target regions was performed tailored to the patients' symptoms. Clinically, no neuropsychiatric effects were seen. Our pilot data suggest a viable therapeutic option to treat the subgroup of TD and EQT IPS and with tremor as the predominant symptom. A clinical study to further investigate this approach ( OPINION: www.clinicaltrials.gov ; NCT02288468) is the focus of our ongoing research. PMID- 26876565 TI - Uncontrolled spread following radiosurgery for a skull base aspergilloma misdiagnosed as schwannoma: is radiosurgery responsible? AB - BACKGROUND: Little is known about the natural history of skull base fungal lesions in immunocompetent individuals and the effect of high-dose radiation on fungal lesions. METHOD AND RESULTS: We report a case where radiosurgery was given to a skull base aspergilloma, mistaking it to be a trigeminal schwannoma. There was dramatic spread of the lesion to periventricular region with significant increase in the skull base lesion. The patient never received steroids. A stereotactic biopsy established the diagnosis, and treatment with voriconazole helped. CONCLUSIONS: It is possible that radiosurgery decreases local immunity due to vascular sclerosis and aids in spread of the fungal lesion, though it is only speculative. This again highlights the importance of establishing the diagnosis prior to radiosurgery. PMID- 26876566 TI - How I do it: the combined petrosectomy. AB - BACKGROUND: Petroclival and ventral brain stem tumors require a complex approach. METHOD: The combined petrosectomy is an epidural transtentorial-transpetrosal otoneurosurgical approach to achieve a retrolabyrinthine presigmoidal approach and an anterior petrosectomy in one single procedure. The different steps of this approach are described and illustrated by figures and a video. The indications and limitations of the technique are presented. CONCLUSION: The combined petrosectomy offers multiple corridors to the petroclival region and ventral brainstem while preserving the intrapetrous neurotological structures. Meticulous stepwise bony resection optimizing the dural opening and preservation of veins contributes to reducing the risk inherent to this technique. PMID- 26876568 TI - Activity-dependent actin dynamics are required for the maintenance of long-term plasticity and for synaptic capture. PMID- 26876569 TI - Assessment of conjunctival microvilli abnormality by micro-Raman analysis - by G. Rusciano et al. AB - Conjunctival microvilli are microscopic cellular membrane protrusions on apical epithelial cells, which increase the surface area available for tear adherence. Pathological alterations of microvilli structure affect the tear film stability and, conversely, dysfunctions of tear film composition can lead to a suffering epithelium (dry-eye syndrome). In this work we propose the use of micro-Raman analysis to reveal conjunctival microvilli abnormalities. Samples were obtained by impression cytology from patients by different stage of dry-eye syndrome. Our experimental outcomes demonstrate that Raman analysis, combined with the use of Principal Component Analysis, is able to detect different stages of microvilli reduction. Globally, these results hold promise for the use of Raman analysis for an objective, effective, non-invasive and potentially also in-vivo analysis of the conjunctiva in all the cases of microvilli-related ocular pathologies. PMID- 26876571 TI - Model Dependency of TMAO's Counteracting Effect Against Action of Urea: Kast Model versus Osmotic Model of TMAO. AB - Classical molecular dynamics simulation of GB1 peptide (a 16-residue beta hairpin) in different osmotic environments is studied. Urea is used for denaturation of the peptide, and trimethylamine-N-oxide (TMAO) is used to offset the effect of urea. Protein-urea electrostatic interactions are found to play a major role in protein-denaturation. To emphasize on protein protecting action of TMAO against urea, two different models of TMAO are used, viz., the Kast model and the Osmotic model. We observe that the Osmotic model of TMAO gives the best protection to counteract urea's action when used in ratio 1:2 of urea:TMAO (i.e., reverse ratio). This is because the presence of TMAO makes urea-protein electrostatic interactions more unfavorable. Preferential solvation of TMAO molecules by urea (and water) molecules is also observed, which causes depletion in the number of urea molecules in the vicinity of the protein. The calculations of intraprotein hydrogen bonds between different residues of protein further reveal the breaking of backbone hydrogen bonds of residues 2 and 15 in the presence of urea, and the same is preserved in the presence of TMAO. Free energy landscapes show that the narrowest distribution is obtained for the osmotic TMAO model when used in reverse ratio. PMID- 26876567 TI - Tissue Metabonomic Phenotyping for Diagnosis and Prognosis of Human Colorectal Cancer. AB - Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide and prognosis based on the conventional histological grading method for CRC remains poor. To better the situation, we analyzed the metabonomic signatures of 50 human CRC tissues and their adjacent non-involved tissues (ANIT) using high resolution magic-angle spinning (HRMAS) (1)H NMR spectroscopy together with the fatty acid compositions of these tissues using GC-FID/MS. We showed that tissue metabolic phenotypes not only discriminated CRC tissues from ANIT, but also distinguished low-grade tumor tissues (stages I-II) from the high-grade ones (stages III-IV) with high sensitivity and specificity in both cases. Metabonomic phenotypes of CRC tissues differed significantly from that of ANIT in energy metabolism, membrane biosynthesis and degradations, osmotic regulations together with the metabolism of proteins and nucleotides. Amongst all CRC tissues, the stage I tumors exhibited largest differentiations from ANIT. The combination of the differentiating metabolites showed outstanding collective power for differentiating cancer from ANIT and for distinguishing CRC tissues at different stages. These findings revealed details in the typical metabonomic phenotypes associated with CRC tissues nondestructively and demonstrated tissue metabonomic phenotyping as an important molecular pathology tool for diagnosis and prognosis of cancerous solid tumors. PMID- 26876572 TI - Preface for International Journal of Eating Disorders special issue medical complications in eating disorders. PMID- 26876570 TI - Contact radiotherapy boost in association with 'watch and wait' for rectal cancer: initial experience and outcomes from a shared programme between a district general hospital network and a regional oncology centre. AB - AIM: Recent data have highlighted the potential of more intensive neoadjuvant protocols to increase and sustain the rate of complete response in rectal cancer managed nonoperatively. This study aimed to review the outcome of all patients from our district general hospitals network who had received standard neoadjuvant therapy and were additionally referred to a centre of excellence for contact X ray brachytherapy or high-dose-rate brachytherapy boost. METHOD: A retrospective, chart-based review of all patients co-managed in this manner was performed. Patient details were retrieved from a prospectively maintained departmental database. Indications for treatment, patient outcome and serial data from follow up clinical and radiological assessment were analysed. RESULTS: Seventeen patients treated over a 6-year period were identified. Median follow-up was 20 (5 54) months. Fourteen patients were clinically staged as T2 or T3 and eight were clinically node positive. Three patients died, of whom only one was initially a surgical candidate but refused an exenteration. Of the 14 patients who remain alive, 11 (79%) have a sustained complete (n = 8) or partial (n = 3) response. Two patients had an incomplete response, one is being palliated and the other awaits salvage surgery. One patient underwent abdominoperineal excision for suspected local recurrence. Currently 13 (93%) surviving patients are stoma free. CONCLUSIONS: This series shows that the addition of a radiotherapy boost offered sustained responses and stoma-free survival even in advanced disease and adverse patient populations whilst providing the majority of care closer to home. PMID- 26876574 TI - P38/JNK signaling pathway mediates the fluoride-induced down-regulation of Fam83h. AB - BACKGROUND/AIM: The similar clinical and pathological feature in fluorosis and amelogenesis imperfect with FAM83H mutations imply that excess fluoride could have effects on the expression of FAM83H and could elaborate this process by some signal pathways regulation. The present study aims to investigate the effects of fluoride on Fam83h expression and try to explore the molecular signaling regulation between them as well as the association of high concentration fluoride with mineralization in ameloblast lineage cells. METHODS: Protein expression and signaling pathways of mouse ameloblast-like LS8 cells, exposed to fluoride or MAPK inhibitors, were compared to control cells without exposure. Fam83h, proteins of MAPK signal pathways (ERK, P38 and JNK) were examined by Quantitative real-time PCR and/or Western-blot. ALP activity and ALP staining were used to detect the mineralization in the cells with exposure during 7-day mineralization inducing differentiation. RESULTS: The results showed that Fam83h protein level in LS8 cells decreased in the presence of fluoride and MAPK inhibitors. Down regulation of Fam83h by fluoride was related to suppression of JNK and P38 phosphorylation, and the descending degree of P38 was more obvious. Fluoride and MAPK inhibitors treatment significantly decreased the mineralization level in LS8 cells. CONCLUSION: The findings suggest that JNK and P38 could be key regulatory element for Fam83h expression, and that LS8 cells can respond to fluoride by down regulating Fam83h expression through the regulation of JNK and p38 signaling pathways. PMID- 26876573 TI - Noninvasive diagnosis and monitoring of mutations by deep sequencing of circulating tumor DNA in esophageal squamous cell carcinoma. AB - Circulating tumor DNA (ctDNA) is becoming an important biomarker in noninvasive diagnosis and monitoring of tumor dynamics. This study tested the feasibility of plasma ctDNA for the non-invasive analysis of tumor mutations in esophageal squamous cell carcinoma (ESCC) by sequencing of tumor, tumor-adjacent, and normal tissue, as well as pre-surgery and post-surgery plasma. Exome sequencing of eight patients identified between 29 and 134 somatic mutations in ESCCs, many of which were also determined in ctDNA. Comparison of pre-surgery and post-surgery plasma has shown that mutations had reduced frequency or disappeared after surgery treatment. We further evaluated the TruSight Cancer sequencing panel by using it to detect mutations in the plasma of three patients. Tumor mutations were only found in one of them. To design a sequencing panel with improved targeting, we identified significantly mutated genes by meta-analysis of 532 ESCC genomes. Our results confirmed the well-known driver genes and found several uncharacterized genes. The new panel consisted of 90 recurrent genes, which theoretically achieved 94% and 75% of sensitivity when detecting at least 1 and 2 mutant genes in ESCC patients, respectively. Our results demonstrate the feasibility of using ctDNA to detect ESCCs and monitor treatment effect. The low-cost and sensitive target panel could facilitate clinical usage of ctDNA as a noninvasive biomarker. PMID- 26876575 TI - MicroRNA-218 promotes high glucose-induced apoptosis in podocytes by targeting heme oxygenase-1. AB - Emerging evidence has demonstrated that microRNAs (miRNAs) play a mediatory role in the pathogenesis of diabetic nephropathy. In this study, we found that miR-218 was upregulated in high glucose (HG) treated podocytes, which are essential components of the glomerular filtration barrier and a major prognostic determinant in diabetic nephropathy. Additionally, up-regulation of miR-218 was accompanied by an increased rate of podocyte death and down-regulation in the level of nephrin, a key marker of podocytes. However, inhibition of miR-218 exerted the opposite effect. In addition, the dual-luciferase reporter assay showed that miR-218 directly targeted the 3'-untranslated region of heme oxygenase-1 (HO-1), and further study confirmed an increase of HO-1 in HG-treated podocytes transfected with anti-miR-218. Knockdown of HO-1 blocked the anti apoptotic effect of anti-miR-218. Furthermore, inhibition of miR-218 was associated with decreased expression of the known pro-apoptotic molecule p38 mitogen-activated protein kinase (p38-MAPK) activation. Following preconditioning with SB203580, an inhibitor of p38-MAPK, the stimulatory effect of HG on podocyte apoptosis was strikingly ameliorated. These findings suggested that miR-218 accelerated HG-induced podocyte apoptosis through directly down-regulating HO-1 and facilitating p38-MAPK activation. PMID- 26876576 TI - Autophagy in allografts rejection: A new direction? AB - Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation. PMID- 26876577 TI - O-GlcNAc regulates NEDD4-1 stability via caspase-mediated pathway. AB - O-GlcNAc modification of cytosolic and nuclear proteins regulates essential cellular processes such as stress responses, transcription, translation, and protein degradation. Emerging evidence indicates O-GlcNAcylation has a dynamic interplay with ubiquitination in cellular regulation. Here, we report that O GlcNAc indirectly targets a vital E3 ubiquitin ligase enzyme of NEDD4-1. The protein level of NEDD4-1 is accordingly decreased following an increase of overall O-GlcNAc level upon PUGNAc or glucosamine stimulation. O-GlcNAc transferase (OGT) knockdown, overexpression and mutation results confirm that the stability of NEDD4-1 is negatively regulated by cellular O-GlcNAc. Moreover, the NEDD4-1 degradation induced by PUGNAc or GlcN is significantly inhibited by the caspase inhibitor. Our study reveals a regulation mechanism of NEDD4-1 stability by O-GlcNAcylation. PMID- 26876578 TI - STAT5A is regulated by DNA damage via the tumor suppressor p53. AB - Here we report that the STAT5A transcription factor is a direct p53 transcriptional target gene. STAT5A is well expressed in p53 wild type cells but not in p53-null cells. Inhibition of p53 reduces STAT5A expression. DNA damaging agents such as doxorubicin also induced STAT5A expression in a p53 dependent manner. Two p53 binding sites were mapped in the STAT5A gene and named PBS1 and PBS2; these sites were sufficient to confer p53 responsiveness in a luciferase reporter gene. Chromatin immunoprecipitation experiments revealed that PBS2 has constitutive p53 bound to it, while p53 binding to PBS1 required DNA damage. In normal human breast lobules, weak p53 staining correlated with regions of intense STAT5A staining. Interestingly, in a cohort of triple negative breast tumor tissues there was little correlation between regions of p53 and STAT5A staining, likely reflecting a high frequency of p53 mutations that stabilize the protein in these tumors. We thus reveal an unexpected connection between cytokine signaling and p53. PMID- 26876579 TI - Real-Space Evidence of Rare Guanine Tautomer Induced by Water. AB - Water is vital for life as a solvent. Specifically, it has been well established that DNA molecules are hydrated in vivo, and water has been found to be responsible for the presence of some noncanonical DNA base tautomers. Theoretical investigations have shown that the existence of water could significantly influence the relative stability of different DNA base tautomers, reduce the energy barrier of tautomeric conversions, and thus promote the formation of some rare base tautomers. In this work, we report the real-space experimental evidence of rare base tautomers. From the high-resolution scanning tunneling microscopy imaging, we surprisingly find the formation of the rare guanine tautomer, i.e., G/(3H,7H) form, on the Au(111) surface by delicately introducing water into the system. The key to the formation of this rare tautomer is proposed to be the "water bridge" that largely reduces the energy barriers of intramolecular proton transfer processes as revealed by extensive density functional theory calculations. The real-space experimental evidence and the proposed mechanism make a step forward toward the fundamental understanding of water-assisted base tautomerization processes. PMID- 26876580 TI - Sensitive determination of norepinephrine, epinephrine, dopamine and 5 hydroxytryptamine by coupling HPLC with [Ag(HIO6 )2 ](5-) -luminol chemiluminescence detection. AB - Based on the enhancing effects of norepinephrine (NE), epinephrine (EP), dopamine (DA) and 5-hydroxytryptamine (5-HT) on the chemiluminescence (CL) reaction between [Ag(HIO6 )2 ](5-) and luminol in alkaline solution, a high-performance liquid chromatography (HPLC) method with CL detection was explored for the sensitive determination of monoamine neurotransmitters for the first time. The UV visible absorption spectra were recorded to study the enhancement mechanism of monoamine neurotransmitters on the CL of [Ag(HIO6 )2 ](5-) and luminol reaction. The HPLC separation of NE, EP, DA and 5-HT was achieved with isocratic elution using a mixture of aqueous 0.2% phosphoric acid and methanol (5:95, v/v) within 11.0 min. Under the optimized conditions, the detection limits of NE, EP, DA, and 5-HT were 4.8, 0.9, 1.9 and 2.3 ng/mL, respectively, corresponding to 17.6-96.0 pg for 20 MUL sample injection. The recoveries of monoamine neurotransmitters in rat brain were >95.6% with the precisions expressed by RSD <5.0%. The validated HPLC-CL method was successfully applied for the quantification of NE, EP, DA and 5-HT in rat brain. This method has promising potential for some biological and clinical investigations focusing on the levels of monoamine neurotransmitters. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876581 TI - JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2. PMID- 26876583 TI - Reply by Authors. PMID- 26876582 TI - Re: Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals: R. Zhang, S. Sutcliffe, E. Giovannucci, W. C. Willett, E. A. Platz, B. A. Rosner, J. D. Dimitrakoff and K. Wu J Urol 2015;194:1295-1300. PMID- 26876584 TI - Re: Primary Endoscopic Realignment of Urethral Disruption Injuries-A Double-Edged Sword?: N. V. Johnsen, R. R. Dmochowski, S. Mock, W. S. Reynolds, D. F. Milam and M. R. Kaufman J Urol 2015;194:1022-1026. PMID- 26876585 TI - Re: Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer: M. L. Blute, Jr., T. J. Rushmer, F. Shi, B. J. Fuller, E. J. Abel, D. F. Jarrard and T. M. Downs J Urol 2015;194:1214-1219. PMID- 26876587 TI - Reply by Authors. PMID- 26876586 TI - Re: Transperineal Template Guided Prostate Biopsy Selects Candidates for Active Surveillance-How Many Cores are Enough?: K. N. Pham, C. R. Porter, K. Odem-Davis, E. M. Wolff, C. Jeldres, J. T. Wei and T. M. Morgan J Urol 2015;194:674-679. PMID- 26876588 TI - Reply by Authors. PMID- 26876589 TI - Reply by Authors. PMID- 26876590 TI - Infiltration of lymphocyte subpopulations into cancer microtissues as a tool for the exploration of immunomodulatory agents and biomarkers. AB - INTRODUCTION: The interaction between the immune system and malignant diseases is a proven key target for cancer therapy. We describe an innovative 3D cell culture system comprising both immune and cancer cells to evaluate their interaction and immune cell infiltration to provide an innovative in vitro screening of immunomodulatory agents and biomarkers. METHODS: 3D tumor microtissues were cultivated using a hanging drops system. Human non-small-cell lung cancer cell lines were incubated for 7 days to form microtissues. On day 5, peripheral blood mononuclear cells (PBMC) were added with or without interleukin-2 (IL-2) for 24 or 48h. Viability of cancer cells and the infiltrating PBMC subpopulations were investigated by flow cytometry. Aggregation of tumor cells and PBMC and the infiltration of the PBMC into the tumor microtissues were analyzed by immunohistochemistry. Quantification of infiltration was measured by applying the TissueFAXS system. RESULTS: Immunohistochemistry revealed PBMC infiltration in all cell lines which increased under IL-2 stimulation. Analysis of infiltrating populations showed both lymphocyte subpopulations and monocytes within the tumor microtissues. In all three co-cultures, CD3+CD8+ and CD3+CD8+CD45R0+CD28+ lymphocytes were increased with IL-2, whereas CD3+CD8+CD45R0-CD28+ PBMCs were decreased with and without IL-2 stimulation. CONCLUSION: In summary, we present a novel cell culture system to study the interaction between cancer cells and immune cells in 3-dimensional microtissues. In addition, we report for the first time an in vitro infiltration assay based on 3D microtissues. This model has the potential to provide a tool for ex-vivo drug testing and biomarker screening of immunomodulatory agents. PMID- 26876591 TI - TGF-beta signalling in tumour associated macrophages. AB - Tumour associated macrophages (TAM) represent an important component of tumour stroma. They develop under the influence of tumour microenvironment where transforming growth factor (TGF)beta is frequently present. Activities of TAM regulated by TGFbeta stimulate proliferation of tumour cells and lead to tumour immune escape. Despite high importance of TGFbeta-induction of TAM activities till now our understanding of the mechanism of this induction is limited. We have previously developed a model of type 2 macrophages (M2) resembling certain properties of TAM. We established that in M2 TGFbetaRII is regulated on the level of subcellular sorting by glucocorticoids. Further studies revealed that in M2 with high levels of TGFbetaRII on the surface TGFbeta activates not only its canonical Smad2/3-mediated signaling, but also Smad1/5-mediated signaling, what is rather typical for bone morphogenetic protein (BMP) stimulation. Complexity of macrophage populations, however, allows assumption that TGFbeta signalling may function in different ways depending on the functional state of the cell. To understand the peculiarities of TGFbeta signalling in human TAMs experimental systems using primary cells have to be developed and used together with the modern mathematical modelling approaches. PMID- 26876592 TI - Complete response to gemtuzumab ozogamicin in a patient with refractory mast cell leukemia. PMID- 26876593 TI - Interleukin-15 deficiency promotes the development of T-cell acute lymphoblastic leukemia in non-obese diabetes mice with severe combined immunodeficiency. PMID- 26876594 TI - Clonal history of a cord blood donor cell leukemia with prenatal somatic JAK2 V617F mutation. PMID- 26876595 TI - The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. AB - Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the alpha-ketoglutarate (alpha-KG) dehydrogenase complex (KGDHC), which converts alpha-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of alpha-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy. PMID- 26876597 TI - Cryopreservation of ovaries from neonatal marmoset monkeys. AB - The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID- 26876599 TI - Challenges in RNA Structural Modeling and Design. PMID- 26876596 TI - DNMT3A(R882H) mutant and Tet2 inactivation cooperate in the deregulation of DNA methylation control to induce lymphoid malignancies in mice. AB - TEN-ELEVEN-TRANSLOCATION-2 (TET2) and DNA-METHYLTRANSFERASE-3A (DNMT3A), both encoding proteins involved in regulating DNA methylation, are mutated in hematological malignancies affecting both myeloid and lymphoid lineages. We previously reported an association of TET2 and DNMT3A mutations in progenitors of patients with angioimmunoblastic T-cell lymphomas (AITL). Here, we report on the cooperative effect of Tet2 inactivation and DNMT3A mutation affecting arginine 882 (DNMT3A(R882H)) using a murine bone marrow transplantation assay. Five out of eighteen primary recipients developed hematological malignancies with one mouse developing an AITL-like disease, two mice presenting acute myeloid leukemia (AML) like and two others T-cell acute lymphoblastic leukemia (T-ALL)-like diseases within 6 months following transplantation. Serial transplantations of DNMT3A(R882H) Tet2(-/-) progenitors led to a differentiation bias toward the T cell compartment, eventually leading to AITL-like disease in 9/12 serially transplanted recipients. Expression profiling suggested that DNMT3A(R882H) Tet2( /-) T-ALLs resemble those of NOTCH1 mutant. Methylation analysis of DNMT3A(R882H) Tet2(-/-) T-ALLs showed a global increase in DNA methylation affecting tumor suppressor genes and local hypomethylation affecting genes involved in the Notch pathway. Our data confirm the transformation potential of DNMT3A(R882H) Tet2(-/-) progenitors and represent the first cooperative model in mice involving Tet2 inactivation driving lymphoid malignancies. PMID- 26876598 TI - The ROS-generating oxidase Nox1 is required for epithelial restitution following colitis. AB - Accumulating evidence suggests that reactive oxygen species (ROS) generated by endogenous metabolic enzymes are involved in a variety of intracellular mechanisms. In particular, superoxide-generating NADPH oxidase (Nox) 1 is highly expressed in the colon and has been implicated in physiological and pathophysiological states of colon tissues. However, its role in tissue repair following colitis has not been fully elucidated. Our study using experimental colitis in mice showed that repair of the mucosal layer did not occur in Nox1 deficient mice following dextran sulfate sodium-induced colitis. This was accompanied by inhibition of proliferation, cell survival, migration, and terminal differentiation (generation of goblet cells) of crypt progenitor cells, as determined by histochemical analyses. Furthermore, Nox1 expression as well as ROS production in the colon crypt was increased during the repair process, and Nox1 deficiency suppressed these events. The results suggest that Nox1 promotes colon mucosal wound repair by sustaining the bioactivity of crypt progenitor cells and plays a crucial role in the epithelial restitution in the case of damage associated with colitis. PMID- 26876601 TI - Homo-trimeric Structure of the Type IVb Minor Pilin CofB Suggests Mechanism of CFA/III Pilus Assembly in Human Enterotoxigenic Escherichia coli. AB - In gram-negative bacteria, the assembly of type IV pilus (T4P) and the evolutionally related pseudopilus of type II secretion system involves specialized structural proteins called pilins and pseudopilins, respectively, and is dynamically regulated to promote bacterial pathogenesis. Previous studies have suggested that a structural "tip"-like hetero-complex formed through the interaction of at least three minor (pseudo) pilins plays an important role in this process, while some members of the pathogenic type IVb subfamily are known to have only one such minor pilin subunit whose function is still unknown. Here, we determined the crystal structure of the type IVb minor pilin CofB of colonization factor antigen/III from human enterotoxigenic Escherichia coli at 1.88-A resolution. The crystal structure, in conjunction with physicochemical analysis in solution, reveals a symmetrical homo-trimeric arrangement distinct from the hetero-complexes of minor (pseudo) pilins observed in other T4P and type II secretion systems. Each CofB monomer adopts a unique three-domain architecture, in which the C-terminal beta-sheet-rich lectin domain can effectively initiate trimer association of its pilin-like N-terminal domain through extensive hydrophobic interactions followed by domain swapping at the central hinge-like domain. Deletion of cofB produces a phenotype with no detectable pili formation on the cell surface, while molecular modeling indicates that the characteristic homo-trimeric structure of CofB is well situated at the pilus tip of colonization factor antigen/III formed by the major pilin CofA, suggesting a role for the minor pilin in the efficient initiation of T4P assembly. PMID- 26876602 TI - Novel helical assembly in arginine methyltransferase 8. AB - Protein arginine methyltransferase 8 (PRMT8) is unique among PRMTs, as it is specifically expressed in brain and localized to the plasma membrane via N terminal myristoylation. Here, we describe the crystal structure of human PRMT8 (hPRMT8) at 3.0-A resolution. The crystal structure of hPRMT8 exhibited a novel helical assembly. Biochemical, biophysical and mutagenesis experiments demonstrated that hPRMT8 forms an octamer in solution. This octameric structure is necessary for proper localization to the plasma membrane and efficient methyltransferase activity. The helical assembly might be a relevant quaternary form for hPRMT1, which is the predominant PRMT in mammalian cells and most closely related to hPRMT8. PMID- 26876600 TI - Recruitment, Duplex Unwinding and Protein-Mediated Inhibition of the Dead-Box RNA Helicase Dbp2 at Actively Transcribed Chromatin. AB - RNA helicases play fundamental roles in modulating RNA structures and facilitating RNA-protein (RNP) complex assembly in vivo. Previously, our laboratory demonstrated that the DEAD-box RNA helicase Dbp2 in Saccharomyces cerevisiae is required to promote efficient assembly of the co-transcriptionally associated mRNA-binding proteins Yra1, Nab2, and Mex67 onto poly(A)(+)RNA. We also found that Yra1 associates directly with Dbp2 and functions as an inhibitor of Dbp2-dependent duplex unwinding, suggestive of a cycle of unwinding and inhibition by Dbp2. To test this, we undertook a series of experiments to shed light on the order of events for Dbp2 in co-transcriptional mRNP assembly. We now show that Dbp2 is recruited to chromatin via RNA and forms a large, RNA-dependent complex with Yra1 and Mex67. Moreover, single-molecule fluorescence resonance energy transfer and bulk biochemical assays show that Yra1 inhibits unwinding in a concentration-dependent manner by preventing the association of Dbp2 with single-stranded RNA. This inhibition prevents over-accumulation of Dbp2 on mRNA and stabilization of a subset of RNA polymerase II transcripts. We propose a model whereby Yra1 terminates a cycle of mRNP assembly by Dbp2. PMID- 26876604 TI - The RNA Polymerase II CTD: The Increasing Complexity of a Low-Complexity Protein Domain. AB - The largest subunit of RNA polymerase II contains a C-terminal domain (CTD) that plays key roles in coordinating transcription with co-transcriptional events. The heptapeptide repeats that form the CTD are dynamically phosphorylated on serine, tyrosine and threonine residues during the various steps of transcription, thereby regulating the recruitment of various proteins involved in gene expression. In this "Perspective," we review the recent literature related to the function of the CTD, to CTD kinases (Kin28, CDK7, CDK9, CDK12, ERK1/2 and DYRK1A) and to CTD phosphatases (Rtr1, RPAP2, Ssu72, Fcp1 and Gcl7). We discuss unresolved and controversial issues and try to provide constructive suggestions. This review also highlights emerging themes in the CTD field, such as crosstalk and feedback mechanisms, as well as gene-specific and tissue-specific functions of the CTD. Finally, promising therapeutic avenues for a recently developed CTD kinase inhibitor are discussed. PMID- 26876603 TI - Mechanisms of Selective Autophagy. AB - Selective autophagy contributes to intracellular homeostasis by mediating the degradation of cytoplasmic material such as aggregated proteins, damaged or over abundant organelles, and invading pathogens. The molecular machinery for selective autophagy must ensure efficient recognition and sequestration of the cargo within autophagosomes. Cargo specificity can be mediated by autophagic cargo receptors that specifically bind the cargo material and the autophagosomal membrane. Here we review the recent insights into the mechanisms that enable cargo receptors to confer selectivity and exclusivity to the autophagic process. We also discuss their different roles during starvation-induced and selective autophagy. We propose to classify autophagic events into cargo-independent and cargo-induced autophagosome formation events. PMID- 26876605 TI - Early development of synchrony in cortical activations in the human. AB - Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. PMID- 26876606 TI - Ataxin-1 regulates proliferation of hippocampal neural precursors. AB - Polyglutamine expansion in the protein ATAXIN-1 (ATXN1) causes spinocerebellar ataxia type 1 (SCA1), an inherited neurodegenerative disease characterized by motor deficits, cognitive impairment and depression. Although ubiquitously expressed, mutant ATXN1 causes neurodegeneration primarily in the cerebellum, which is responsible for the observed motor deficits. The role of ATXN1 outside of the cerebellum and the causes of cognitive deficits and depression in SCA1 are less understood. In this study, we demonstrate a novel role of ATXN1 in the hippocampus as a regulator of adult neurogenesis. Adult hippocampal neurogenesis is the process of generating new hippocampal neurons and is linked to cognition and mood. We found that loss of ATXN1 causes a decrease in hippocampal neurogenesis in ATXN1 null (Atxn1(-/-)) mice. This decrease was caused by reduced proliferation of neural precursors in the hippocampus of Atxn1(-/-) mice, and persisted even when Atxn1(-/-) hippocampal neural precursors were removed from their natural environment and grown in vitro, suggesting that ATXN1 affects proliferation in a cell-autonomous manner. Moreover, expression of ATXN1 with a pathological polyglutamine (polyQ) expansion in wild-type neural precursor cells inhibited their proliferation. Our data establish a novel role for ATXN1 in the hippocampus as an intrinsic regulator of precursor cell proliferation, and suggest a mechanism by which polyQ expansion and loss of ATXN1 affect hippocampal function, potentially contributing to cognitive deficits and depression. These results indicate that while depletion of ATXN1 is a promising therapeutic approach to treat the cerebellar aspects of SCA1, this approach should be employed with caution given the potential for side effects on hippocampal function with loss of wild-type ATXN1. PMID- 26876609 TI - Manipulation of nanofiber-based beta-galactosidase nanoenvironment for enhancement of galacto-oligosaccharide production. AB - The nanoenvironment of nanobiocatalysts, such as local hydrophobicity, pH and charge density, plays a significant role in optimizing the enzymatic selectivity and specificity. In this study, Kluyveromyces lactis beta-galactosidase (Gal) was assembled onto polystyrene nanofibers (PSNFs) to form PSNF-Gal nanobiocatalysts. We proposed that local hydrophobicity on the nanofiber surface could expel water molecules so that the transgalactosylation would be preferable over hydrolysis during the bioconversion of lactose, thus improve the galacto-oligosaccharides (GOS) yield. PSNFs were fabricated by electro-spinning and the operational parameters were optimized to obtain the nanofibers with uniform size and ordered alignment. The resulting nanofibers were functionalized for enzyme immobilization through a chemical oxidation method. The functionalized PSNF improved the enzyme adsorption capacity up to 3100 mg/g nanofiber as well as enhanced the enzyme stability with 80% of its original activity. Importantly, the functionalized PSNF Gal significantly improved the GOS yield and the production rate was up to 110 g/l/h in comparison with 37 g/l/h by free beta-galactosidase. Our research findings demonstrate that the localized nanoenvironment of the PSNF-Gal nanobiocatalysts favour transgalactosylation over hydrolysis in lactose bioconversion. PMID- 26876608 TI - Dorsal premotor activity and connectivity relate to action selection performance after stroke. AB - Compensatory activation in dorsal premotor cortex (PMd) during movement execution has often been reported after stroke. However, the role of PMd in the planning of skilled movement after stroke has not been well studied. The current study investigated the behavioral and neural response to the addition of action selection (AS) demands, a motor planning process that engages PMd in controls, to movement after stroke. Ten individuals with chronic, left hemisphere stroke and 16 age-matched controls made a joystick movement with the right hand under two conditions. In the AS condition, participants moved right or left based on an abstract, visual rule; in the execution only condition, participants moved in the same direction on every trial. Despite a similar behavioral response to the AS condition (increase in reaction time), brain activation differed between the two groups: the control group showed increased activation in left inferior parietal lobule (IPL) while the stroke group showed increased activation in several right/contralesional regions including right IPL. Variability in behavioral performance between participants was significantly related to variability in brain activation. Individuals post-stroke with relatively poorer AS task performance showed greater magnitude of activation in left PMd and dorsolateral prefrontal cortex (DLPFC), increased left primary motor cortex-PMd connectivity, and decreased left PMd-DLPFC connectivity. Changes in the premotor-prefrontal component of the motor network during complex movement conditions may negatively impact the performance and learning of skilled movement and may be a prime target for rehabilitation protocols aimed at improving the function of residual brain circuits after stroke. Hum Brain Mapp 37:1816-1830, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26876607 TI - Regulation of neuronal chloride homeostasis by neuromodulators. AB - KCC2 is the central regulator of neuronal Cl(-) homeostasis, and is critical for enabling strong hyperpolarizing synaptic inhibition in the mature brain. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous disease states including epilepsy, neuropathic pain and neuropsychiatric disorders. The current holy grail of KCC2 biology is to identify how we can rescue KCC2 hypofunction in order to restore physiological levels of synaptic inhibition and neuronal network activity. It is becoming increasingly clear that diverse cellular signals regulate KCC2 surface expression and function including neurotransmitters and neuromodulators. In the present review we explore the existing evidence that G-protein-coupled receptor (GPCR) signalling can regulate KCC2 activity in numerous regions of the nervous system including the hypothalamus, hippocampus and spinal cord. We present key evidence from the literature suggesting that GPCR signalling is a conserved mechanism for regulating chloride homeostasis. This evidence includes: (1) the activation of group 1 metabotropic glutamate receptors and metabotropic Zn(2+) receptors strengthens GABAergic inhibition in CA3 pyramidal neurons through a regulation of KCC2; (2) activation of the 5-hydroxytryptamine type 2A serotonin receptors upregulates KCC2 cell surface expression and function, restores endogenous inhibition in motoneurons, and reduces spasticity in rats; and (3) activation of A3A-type adenosine receptors rescues KCC2 dysfunction and reverses allodynia in a model of neuropathic pain. We propose that GPCR-signals are novel endogenous Cl(-) extrusion enhancers that may regulate KCC2 function. PMID- 26876611 TI - The sunflower transcription factor HaHB11 improves yield, biomass and tolerance to flooding in transgenic Arabidopsis plants. AB - HaHB11 is a member of the sunflower homeodomain-leucine zipper I subfamily of transcription factors. The analysis of a sunflower microarray hybridized with RNA from HaHB11-transformed leaf-disks indicated the regulation of many genes encoding enzymes from glycolisis and fermentative pathways. A 1300bp promoter sequence, fused to the GUS reporter gene, was used to transform Arabidopsis plants showing an induction of expression after flooding treatments, concurrently with HaHB11 regulation by submergence in sunflower. Arabidopsis transgenic plants expressing HaHB11 under the control of the CaMV 35S promoter and its own promoter were obtained and these plants exhibited significant increases in rosette and stem biomass. All the lines produced more seeds than controls and particularly, those of high expression level doubled seeds yield. Transgenic plants also showed tolerance to flooding stress, both to submergence and waterlogging. Carbohydrates contents were higher in the transgenics compared to wild type and decreased less after submergence treatments. Finally, transcript levels of selected genes involved in glycolisis and fermentative pathways as well as the corresponding enzymatic activities were assessed both, in sunflower and transgenic Arabidopsis plants, before and after submergence. Altogether, the present work leads us to propose HaHB11 as a biotechnological tool to improve crops yield, biomass and flooding tolerance. PMID- 26876610 TI - Hyperforin production in Hypericum perforatum root cultures. AB - Extracts of the medicinal plant Hypericum perforatum are used to treat depression and skin irritation. A major API is hyperforin, characterized by sensitivity to light, oxygen and temperature. Total synthesis of hyperforin is challenging and its content in field-grown plants is variable. We have established in vitro cultures of auxin-induced roots, which are capable of producing hyperforin, as indicated by HPLC-DAD and ESI-MS analyses. The extraction yield and the productivity upon use of petroleum ether after solvent screening were ~5 mg/g DW and ~50 mg/L culture after six weeks of cultivation. The root cultures also contained secohyperforin and lupulones, which were not yet detected in intact plants. In contrast, they lacked another class of typical H. perforatum constituents, hypericins, as indicated by the analysis of methanolic extracts. Hyperforins and lupulones were stabilized and enriched as dicyclohexylammonium salts. Upon up-scaling of biomass production and downstream processing, H. perforatum root cultures may provide an alternative platform for the preparation of medicinal extracts and the isolation of APIs. PMID- 26876612 TI - Changes in melanocytic nevi after laser treatment evaluated by dermoscopy and reflectance confocal microscopy. PMID- 26876613 TI - Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: A new implication of skin cancer prevention. AB - Ultraviolet B (UVB) radiation is the major environmental risk factor for developing skin cancer, the most common cancer worldwide, which is characterized by aberrant activation of Akt/mTOR (mammalian target of rapamycin). Importantly, the link between UV irradiation and mTOR signaling has not been fully established. Apigenin is a naturally occurring flavonoid that has been shown to inhibit UV-induced skin cancer. Previously, we have demonstrated that apigenin activates AMP-activated protein kinase (AMPK), which leads to suppression of basal mTOR activity in cultured keratinocytes. Here, we demonstrated that apigenin inhibited UVB-induced mTOR activation, cell proliferation and cell cycle progression in mouse skin and in mouse epidermal keratinocytes. Interestingly, UVB induced mTOR signaling via PI3K/Akt pathway, however, the inhibition of UVB induced mTOR signaling by apigenin was not Akt-dependent. Instead, it was driven by AMPK activation. In addition, mTOR inhibition by apigenin in keratinocytes enhanced autophagy, which was responsible, at least in part, for the decreased proliferation in keratinocytes. In contrast, apigenin did not alter UVB-induced apoptosis. Taken together, our results indicate the important role of mTOR inhibition in UVB protection by apigenin, and provide a new target and strategy for better prevention of UV-induced skin cancer. PMID- 26876615 TI - EZH2, an on-off valve in signal network of tumor cells. AB - Enhancer Zeste 2 (EZH2) is a histone methyltransferase catalyzing histone H3K27me3 to mediate gene silence. It is implicated in governing various biological behaviors of human malignancies. In this review, we over-review EZH2 serves as an "on-off valve"--not only as a critical epigenetic repressor, but as a brand-new activator for specific downstream targets as well. Time and space it "switching on-off" depends on the context and its cellular type. Moreover, EZH2 could act as a Tumor-Defender under certain circumstances. Moreover, the "Mutual Inhibition" relationship between EZH2 and microRNAs is elaborated. In addition, we focus on different functions of phosphorylatied EZH2 in tumor cells. Finally, EZH2 inhibitors are summarized and newly-discovered strategies of targeting-EZH2 treatment are prospected. PMID- 26876614 TI - Shoc2-tranduced ERK1/2 motility signals--Novel insights from functional genomics. AB - The extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway plays a central role in defining various cellular fates. Scaffold proteins modulating ERK1/2 activity control growth factor signals transduced by the pathway. Here, we analyzed signals transduced by Shoc2, a critical positive modulator of ERK1/2 activity. We found that loss of Shoc2 results in impaired cell motility and delays cell attachment. As ERKs control cellular fates by stimulating transcriptional response, we hypothesized that the mechanisms underlying changes in cell adhesion could be revealed by assessing the changes in transcription of Shoc2-depleted cells. Using quantitative RNA-seq analysis, we identified 853 differentially expressed transcripts. Characterization of the differentially expressed genes showed that Shoc2 regulates the pathway at several levels, including expression of genes controlling cell motility, adhesion, crosstalk with the transforming growth factor beta (TGFbeta) pathway, and expression of transcription factors. To understand the mechanisms underlying delayed attachment of cells depleted of Shoc2, changes in expression of the protein of extracellular matrix (lectin galactoside-binding soluble 3-binding protein; LGALS3BP) were functionally analyzed. We demonstrated that delayed adhesion of the Shoc2 depleted cells is a result of attenuated expression and secretion of LGALS3BP. Together our results suggest that Shoc2 regulates cell motility by modulating ERK1/2 signals to cell adhesion. PMID- 26876616 TI - The value of integrating pre-clinical data to predict nausea and vomiting risk in humans as illustrated by AZD3514, a novel androgen receptor modulator. AB - Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally administered compound that inhibits androgen receptor signaling and down regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose responsive "pica" behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting. PMID- 26876618 TI - BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity. AB - Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MTT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma. PMID- 26876619 TI - Instruments for measuring meaningful learning in healthcare students: a systematic psychometric review. AB - AIM: To identify, evaluate and describe the psychometric properties of instruments that measure learning outcomes in healthcare students. BACKGROUND: Meaningful learning is an active process that enables a wider and deeper understanding of concepts. It is the result of an interaction between new and prior knowledge and produces a long-standing change in knowledge and skills. In the field of education, validated and reliable instruments for assessing meaningful learning are needed. DESIGN: A psychometric systematic review. DATA SOURCES: MEDLINE CINAHL, SCOPUS, ERIC, Cochrane Library, Psychology & Behavioural Sciences Collection Database from 1990-December 2013. REVIEW METHOD: Using pre determined inclusion criteria, three reviewers independently identified studies for full-text review. Then they extracted data for quality appraisal and graded instrument validity using the Consensus-based Standards for the selection of the health status Measurement INstruments checklist and the Psychometric Grading Framework. RESULTS: Of the 57 studies identified for full-text review, 16 met the inclusion criteria and 13 different instruments were assessed. Following quality assessment, only one instrument was considered of good quality but it measured meaningful learning only in part; the others were either fair or poor. The Psychometric Grading Framework indicated that one instrument was weak, while the others were very weak. No instrument displayed adequate validity. CONCLUSIONS: The systematic review produced a synthesis of the psychometric properties of tools that measure learning outcomes in students of healthcare disciplines. Measuring learning outcomes is very important when educating health professionals. The identified tools may constitute a starting point for the development of other assessment tools. PMID- 26876617 TI - Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro. AB - Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 MUM, 36 MUM, and 100 MUM) for 48 and 96 h. Every 24h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 MUM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-alpha-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. PMID- 26876620 TI - Could larger diameter of 4th generation ceramic bearing decrease the rate of dislocation after THA? AB - BACKGROUND: Fourth generation (Delta) ceramic bearing was developed to reduce dislocation after total hip arthroplasty (THA) by increasing the head diameter. We tested a hypothesis that 32/36 mm Delta ceramic bearing decreases the dislocation rate. We also evaluated ceramic-related complications and early outcome of this thin liner-on-large head ceramic bearing. METHODS: We performed a prospective study on patients who underwent THA with use of 32/36 mm Delta ceramic bearing. The dislocation rate was compared with the historical dislocation rate of third generation 28 mm ceramic bearing. We also evaluated ceramic fracture, squeak, short-term results and survival. Follow-up period was minimum 2 years. RESULTS: Between April 2010 and February 2012, we enrolled 250 consecutive patients (278 hips). All patients received cementless prostheses. Four patients (4 hips) who received metal shells <= 46 mm and 28 mm heads were excluded. Three patients died and 2 patients were lost within 2 years. The remaining 241 patients (269 hips) were followed for 24-46 months. There were 142 men (161 hips) and 99 women (108 hips) with a mean age of 53.7 years (range, 17 75 years) at the index operation. Dislocation occurred in three hips (1.1%). An old age was a risk factor for dislocation. Ceramic fracture and squeaking did not occur in any patient. Mean Harris hip score was 90.3 points at the latest follow up. All acetabular and femoral components had bone-ingrowth stability. No hip had detectable wear or osteolysis. The survival was 99.3% in the best case scenario and 97.8% in the worst at 48 months. CONCLUSIONS: Total hip arthroplasty with use of 32/36 mm Delta ceramic bearing showed lower incidence of hip dislocation compared with 28 mm third generation ceramic bearing. A caution should be paid to prevent a fall in senile patients even though a large head is used. The short term results of THA with this type of ceramic articulation are encouraging and we did not find any ceramic-related complications. PMID- 26876621 TI - Limited efficacy of COX-2 inhibitors on nerve growth factor and metalloproteinases expressions in human synovial fibroblasts. AB - BACKGROUND: Nerve growth factor (NGF) is associated with arthritic pain and metalloproteinases are implicated in collagen and aggrecan degradation. Although selective COX-2 inhibitors are recommended for the treatment of arthritic diseases, their effects on NGF and metalloproteinases remain unclear. This study investigated the regulations of NGF and metalloproteinases by selective COX-2 inhibitors in isolated human synovial cells. METHODS: The isolated human synovial cells were stimulated with IL-1beta in the presence of selective COX-2 inhibitors (NS-398 or celecoxib) with or without exogenous PGE2 or its receptor (EP1-4) agonists. The expressions of NGF, MMP-1, -3, -13, ADAMTS-4, and -5 were quantified by real-time PCR and their proteins were determined by Western blotting. The amount of PGE2 released was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The IL-1beta inductions of NGF and MMP-1 and MMP-13 were augmented by the COX-2 inhibitors, whereas the inductions of ADAMTS-4 and ADAMTS 5 were inhibited. These actions were reversed by supplementing PGE2 or the EP4 agonist exogenously. CONCLUSION: Our comprehensive analysis revealed that COX-2 inhibitors may be beneficial for suppressing aggrecan degradation and for reducing inflammatory pain by inhibiting PGE2 release, although they may have limited efficacy in suppressing collagen degradation and nerve growth. This study suggests the feedback roles of PGE2 in the negative regulation of NGF and MMP-1 and MMP-13 and the positive regulation of ADAMTS-4 and ADAMTS-5. PMID- 26876622 TI - Topography and ultrasonographic identification of the equine pulmonary vein draining pattern. AB - Information on ultrasound examination of equine pulmonary veins is scarce due to a lack of in-depth anatomical information. Each pulmonary vein drains a specific lung lobe region, after which those veins merge into a collecting antrum, before opening into the left atrium through their respective ostia. The aim of this study was, by using anatomical dissection and silicone casting of equine cardiopulmonary sets, to study the venous drainage of both lungs and the position of the ostia and to investigate whether the ostia can be identified and differentiated using ultrasound. Three out of the four ostia could be observed echocardiographically in the standing horse. The ostium draining the most caudal aspects of both lungs showed little variability, while the ostium draining the rest of the right lung could be used as an easily recognisable landmark, since it was located adjacent to the interatrial septum. The identification of the equine pulmonary vein ostia using ultrasound might allow for the determination of size and flow patterns in the assessment of cardiovascular disease. PMID- 26876623 TI - Pro-inflammatory cytokines: Useful markers for the diagnosis of canine mammary tumours? AB - The aim of the present study was to analyse the expression of 60 pro-inflammatory cytokines as possible markers of malignancy in canine mammary tumours using a human cytokine antibody array. The cytokines were grouped into two different categories: (1) cytokines in which expression indicated the presence of a mammary tumour and (2) cytokines in which expression differentiated between simple mammary adenoma, tubulopapillary carcinoma or complex carcinoma. These data suggest that specific pro-inflammatory cytokines could be useful as tools for the diagnosis of canine mammary tumours. PMID- 26876624 TI - A systematic review and meta-analysis of primary prevention programmes to improve cardio-metabolic risk in non-urban communities. AB - INTRODUCTION: Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) prevention programmes have been effective in urban residents, their effectiveness in non-urban settings, where cardio-metabolic risk is typically elevated, is unknown. We systematically reviewed the effectiveness of primary prevention programmes aimed at reducing risk factors for CVD/T2DM, including blood pressure, body mass index (BMI), blood lipid and glucose, diet, lifestyle, and knowledge in adults residing in non-urban areas. METHODS: Twenty-five manuscripts, globally, from 1990 were selected for review (seven included in the meta-analyses) and classified according to: 1) study design (randomised controlled trial [RCT] or pre-/post-intervention); 2) intervention duration (short [<12months] or long term [>=12months]), and; 3) programme type (community based programmes or non-community-based programmes). RESULTS: Multiple strategies within interventions focusing on health behaviour change effectively reduced cardio-metabolic risk in non-urban individuals. Pre-/post-test design studies showed more favourable improvements generally, while RCTs showed greater improvements in physical activity and disease and risk knowledge. Short-term programmes were more effective than long-term programmes and in pre-/post-test designs reduced systolic blood pressure by 4.02mmHg (95% CI -6.25 to -1.79) versus 3.63mmHg (95% CI -7.34 to 0.08) in long-term programmes. Community-based programmes achieved good results for most risk factors except BMI and (glycated haemoglobin) HbA1c. CONCLUSION: The setting for applying cardio-metabolic prevention programmes is important given its likelihood to influence programme efficacy. Further investigation is needed to elucidate the individual determinants of cardio-metabolic risk in non-urban populations and in contrast to urban populations. PMID- 26876625 TI - Prevention Neuroscience: A new frontier for preventive medicine. AB - Prevention neuroscience may be defined as follows: an interdisciplinary field concerned with the neurobiological factors that influence susceptibility to preventable disease, disability or mortality. It includes, but is not limited to: examination of brain health as an outcome, brain activity as a predictor of health outcomes, brain structures/systems as causal determinants of health outcomes (e.g., health behaviours), and the brain as a mediator of other causal influences (e.g., social conditions) on health outcomes. This commentary describes concepts, theory and research illustrating each of these scenarios using exercise, smoking cessation, dietary behaviour, and health disparities as examples. It is argued that neuroscience may provide both concepts and methods that may be possible (even fruitful) to incorporate into preventive medicine research and health promotion practise. Although public health practitioners and cognitive neuroscientists have not traditionally crossed paths outside of the context of neurodegenerative diseases such as Alzheimer's and other dementias, it is easy to envision a future where many common disease prevention activities involve collaboration between the two disciplines, and the cache of tools available to the preventive medicine expert includes neuroimaging and neuromodulation techniques. PMID- 26876626 TI - An overview of tobacco control and prevention policy status in Africa. AB - Tobacco smoking prevalence remains low in many African countries. However, growing economies and the increased presence of multinational tobacco companies in the African Region have the potential to contribute to increasing tobacco use rates in the future. This paper used data from the 2014 Global Progress Report on implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC), as well as the 2015 WHO report on the global tobacco epidemic, to describe the status of tobacco control and prevention efforts in countries in the WHO African Region relative to the provisions of the WHO FCTC and MPOWER package. Among the 23 countries in the African Region analyzed, there are large variations in the overall WHO FCTC implementation rates, ranging from 9% in Sierra Leone to 78% in Kenya. The analysis of MPOWER implementation status indicates that opportunities exist for the African countries to enhance compliance with WHO recommended best practices for monitoring tobacco use, protecting people from tobacco smoke, offering help to quit tobacco use, warning about the dangers of tobacco, enforcing bans on tobacco advertising and promotion, and raising taxes on tobacco products. If tobacco control interventions are successfully implemented, African nations could avert a tobacco related epidemic, including premature death, disability, and the associated economic, development, and societal costs. PMID- 26876627 TI - Establishing school day pedometer step count cut-points using ROC curves in low income children. AB - Previous research has not established pedometer step count cut-points that discriminate children that meet school day physical activity recommendations using a tri-axial ActiGraph accelerometer criterion. The purpose of this study was to determine step count cut-points that associate with 30min of school day moderate-to-vigorous physical activity (MVPA) in school-aged children. Participants included 1053 school-aged children (mean age=8.4+/-1.8years) recruited from three low-income schools from the state of Utah in the U.S. Physical activity was assessed using Yamax DigiWalker CW600 pedometers and ActiGraph wGT3X-BT triaxial accelerometers that were concurrently worn during school hours. Data were collected at each school during the 2014-2015 school year. Receiver operating characteristic (ROC) curves were used to determine pedometer step count cut-points that associated with at least 30min of MVPA during school hours. Cut-points were determined using the maximum Youden's J statistic (J max). For the total sample, the area-under-the-curve (AUC) was 0.77 (p<0.001) with a pedometer cut-point of 5505 steps (J max=0.46, Sensitivity=63%, Specificity=84%; Accuracy=76%). Step counts showed greater diagnostic ability in girls (AUC=0.81, p<0.001; Cut-point=5306 steps; Accuracy=78.8%) compared to boys (AUC=0.72, p<0.01; Cut-point=5786 steps; Accuracy=71.4%). Pedometer step counts showed good diagnostic ability in girls and fair diagnostic ability in boys for discriminating children that met at least 30min of MVPA during school hours. PMID- 26876628 TI - Does socioeconomic status moderate the relationships between school connectedness with psychological distress, suicidal ideation and attempts in adolescents? AB - OBJECTIVE: Research has indicated that school connectedness acts as a buffer against depressive symptoms and suicidality. However, little is known about the role of socioeconomic status (SES) on these links. The present study examined the moderating role of subjective SES and parental education on the relationships between school connectedness and psychological distress, suicidal ideation and suicide attempts. METHODS: Data were gathered from 4955 participants within the 2013 cycle of the Ontario Students Drug Use and Health Survey, a province-wide repeated school-based survey of students in grade 7 to 12 across Ontario, Canada. RESULTS: Results indicated that higher subjective SES is associated with high levels of school connectedness. Subjective SES is also a significant moderator of the association between school connectedness and psychological distress, but not between school connectedness and suicidal ideation or attempts. At low subjective SES, there was no difference in risk of psychological distress between students with high and low levels of school connectedness. However, at higher subjective SES, students with high levels of school connectedness have lower odds of psychological distress than those with low levels of school connectedness. The associations between school connectedness and each of the mental health outcomes did not significantly vary with parental education. CONCLUSIONS: These findings suggest that the beneficial effects of school connectedness on mental health problems may be more strongly related to adolescents' status beliefs rather than parental education. Future research is needed to better understand the mechanism through which subjective SES and school connectedness influence psychological distress. PMID- 26876629 TI - Association of after school sedentary behaviour in adolescence with mental wellbeing in adulthood. AB - OBJECTIVE: Sedentary behaviour is associated with poorer mental health in adolescence but no studies have followed participants into mid-life. We investigated the association between after-school sedentary behaviours (screen time and homework) in adolescence with mental wellbeing in adulthood when participants were aged 42. METHODS: Participants (n=2038, 59.2% female) were drawn from The 1970 British Cohort Study (BCS70). At age 16 respondents were asked separate questions about how long they spent in three types of screen based activities (TV, video films, computer games) and homework 'after school yesterday'. Mental well-being and psychological distress were assessed at the age 42 sweep in 2012 using the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and Malaise Inventory, respectively. RESULTS: After adjustment for all covariates, participants reporting more than 3h of after school screen time as an adolescent had -1.74 (95% CI, -2.65, -0.83) points on the WEMWBS compared with adults reporting less than 1h screen time as an adolescent. Participants that reported high screen time both at age 16 (>=3h/d) and age 42 (>=3h/d TV viewing) demonstrated even lower scores (-2.91; -4.12, -1.69). Homework was unrelated to wellbeing after adjustment for covariates. The longitudinal association between adolescent screen time and adult psychological distress was attenuated to the null after adjustment for covariates. CONCLUSIONS: Screen time in adolescence was inversely associated with mental wellbeing in adulthood. PMID- 26876631 TI - Obesity prevention and obesogenic behavior interventions in child care: A systematic review. AB - OBJECTIVE: Review peer-reviewed interventions designed to reduce obesity and improve obesogenic behaviors, including physical activity, diet, and screen time, at child care centers. Interventions components and outcomes, study design, duration, use of behavioral theory, and level of social ecological influence are detailed. METHODS: Article searches were conducted from March 2014, October 2014, March 2015, January 2016 across three databases. Eligible interventions were conducted in child care settings, included 3-to-5-year-old children, included an outcome measure of obesity or obesogenic behavior, and published in English. Study design quality was assessed using Stetler's Level of Quantitative Evidence. RESULTS: All unique records were screened (n=4589): 237 articles were assessed for eligibility. Of these, 97 articles describing 71 interventions met inclusion criteria. Forty-four articles included multi-level interventions. Twenty-nine interventions included an outcome measure of obesity. Forty-one interventions included physical activity. Forty-five included diet. Eight included screen time. Fifty-five percent of interventions were Level II (randomized controlled trials), while 37% were Level III (quasi-experimental or pre-post only study design), and 8% were Level IV (non-experimental or natural experiments). Most interventions had the intended effect on the target: obesity 48% (n=14), physical activity 73% (n=30), diet 87% (n=39), and screen time 63% (n=5). CONCLUSION: Summarizing intervention strategies and assessing their effectiveness contributes to the existing literature and may provide direction for practitioners and researchers working with young children in child care. Most interventions produced the targeted changes in obesity and obesity-associated behaviors, supporting current and future efforts to collaborate with early-care centers and professionals for obesity prevention. PMID- 26876630 TI - Use of population-referenced total activity counts percentiles to assess and classify physical activity of population groups. AB - OBJECTIVES: Population-referenced total activity counts per day (TAC/d) percentiles provide public health practitioners a standardized measure of physical activity (PA) volume obtained from an accelerometer that can be compared across populations. The purpose of this study was to describe the application of TAC/d population-referenced percentiles to characterize the PA levels of population groups relative to US estimates. METHODS: A total of 679 adults participating in the 2011 NYC Physical Activity Transit survey wore an ActiGraph accelerometer on their hip for seven consecutive days. Accelerometer-derived TAC/d was classified into age- and gender-specific quartiles of US population referenced TAC/d to compare differences in the distributions by borough (N=5). RESULTS: Males in Brooklyn, Manhattan, and Staten Island had significantly greater TAC/d than US males. Females in Brooklyn and Queens had significantly greater levels of TAC/d compared to US females. The proportion of males in each population-referenced TAC/d quartile varied significantly by borough (chi(2)(12)=2.63, p=0.002), with disproportionately more men in Manhattan and the Bronx found to be in the highest and lowest US population-referenced TAC/d quartiles, respectively. For females, there was no significant difference in US population-reference TAC/d quartile by borough (chi(2)(12)=1.09, p=0.36). CONCLUSIONS: These results demonstrate the utility of population-referenced TAC/d percentiles in public health monitoring and surveillance. These findings also provide insights into the PA levels of NYC residents relative to the broader US population, which can be used to guide health promotion efforts. PMID- 26876633 TI - Moderating effect of gross family income on the association between demographic indicators and active commuting to work in Brazilian adults. AB - OBJECTIVE: To investigate the moderating effect of gross family income on the association between demographic indicators and active commuting to work in Brazilian adults. METHODS: Secondary analysis of the survey "Lifestyle and leisure habits of industry workers" (n=46,981), conducted in 24 Brazilian states (2006-2008). Self-reported information was collected with a previously tested questionnaire. Crude and adjusted logistic regression models were applied to analyze the association between sociodemographic variables (sex, age, marital status, number of children, education, country area and company size) and active commuting to work in different strata of gross family income. To test the moderating effect, an interaction analysis was applied. RESULTS: The proportion of active commuters among low-, medium- and high-income workers was 40.7% (95%CI:40.0%;41.5%), 27.0% (95%CI:26.3;27.6%) and 11.1%, (95%CI:10.5%;11.7%), respectively. The moderating effect of gross family income was confirmed. Men were more likely (OR:1.22 95%CI:1.12;1.32) to commute actively than women among low-income individuals. Active commuting was less likely among older workers in low-(OR30-39:0.90 95%CI: 0.83;0.98; OR>=40: 0.76 95%CI: 0.68;0.85) and medium income strata (OR30-39:0.87 95%CI:0.80;0.95; OR>=40:0.84 95%CI:0.76;0.93) and among married individuals in high-income strata (OR:0.72 95%IC:0.61;0.84). Adults with lower education (ORhigh:10.80 95%CI:8.47;13.77), working in the south (ORhigh:1.93 95%CI:1.53;2.44) and in small companies (ORlow:2.50 95%CI:2.28;2.74) were more likely to commute actively; however, the magnitude of these associations differed at each income strata. CONCLUSION: There was an inverse association between gross family income and active commuting. Gross family income acts as a moderator of the association between demographic indicators and active commuting. PMID- 26876632 TI - Eating behaviors among low-income obese adults in the United States: Does health care provider's advice carry any weight. AB - The U.S. Preventive Task Force recommends that all patients be screened for obesity and given appropriate weight loss advice, if needed, as nutrition counseling by primary care physicians is a key objective for Healthy People 2020. This study assesses the association between health care provider's (HCP) advice to lose weight and eating behaviors among obese individuals. Data were collected using a household survey of adults in five New Jersey cities in 2009-10. Analyses presented are limited to 548 obese participants. Negative-binomial regression analysis determined the association of participants' eating behaviors and HCP's advice to lose weight, after adjusting for the participant's attempt to lose weight and demographic variables. Despite being obese, only 48% of the participants received weight loss advice from their HCP while 68% stated they were attempting to lose weight. HCP's advice to lose weight was associated with increased salad and fruit consumption (PR 1.3, 95% CI 1.06-1.61; PR 1.23, 95% CI 1.02-1.48). Attempting to lose weight was positively associated with a higher consumption of fruit (PR 1.39, 95% CI 1.13-1.72), vegetables (PR 1.22, 95% CI 1.07-1.39), and with eating fruits and vegetables as snacks (PR 1.62, 95% CI 1.28 2.05). Attempting to lose weight was negatively associated with consumption of sweet snacks (PR 0.68, 95% CI 0.49-0.94), sugar sweetened beverages (PR 0.71, 95% CI 0.58-0.87) and fast food (PR 0.77, 95% CI 0.62-0.97). There were no significant interactions between HCP's advice and attempts to lose weight. Obese adult's attempt to lose weight, and not HCP's advice to lose weight, was a predictor for healthy eating behaviors. Interventions in medical practices should train HCPs on effective strategies for motivating obese patients to adopt healthier lifestyles. PMID- 26876634 TI - Pustular prurigo pigmentosa treated with doxycycline. PMID- 26876636 TI - The clinical significance of para-aortic nodal dissection for advanced gastric cancer. AB - BACKGROUND: Advanced gastric cancer with the risk of extensive nodal involvement has a poor prognosis even after radical surgery. We aimed to comprehensively review the clinical significance of extended radical dissection. METHODS: Between 1990 and 1999, 232 patients underwent radical gastrectomy with D2 plus para aortic lymph node dissection at the National Cancer Center Hospital in Tokyo. We analyzed the short-term surgical and long-term oncological outcomes of these operations. RESULTS: Major complications occurred in 34 patients (14.7%). Median operation time was 325 min (range: 182-555) and median blood loss was 715 ml (range: 95-4457). There were 2 (0.9%) hospital deaths. Nodal involvement of the para-aortic area was seen in 33 patients (14.2%). The overall 5- and 10-year survival rates in patients with para-aortic node involvement were 21.2 and 15.2%, respectively. Multivariate analysis of patients with para-aortic node involvement revealed advanced age and metastasis in the interaorticocaval lymph nodes above the left renal vein to be independent risk factors impacting overall survival. CONCLUSIONS: PAN dissection has limited applicability and effectiveness to the patients with advanced gastric cancer. Above all, advanced age and metastasis in the interaorticocaval lymph nodes above the left renal vein are significant poor prognostic factor even after radical resection. PMID- 26876635 TI - Zebrafish Collagen Type I: Molecular and Biochemical Characterization of the Major Structural Protein in Bone and Skin. AB - Over the last years the zebrafish imposed itself as a powerful model to study skeletal diseases, but a limit to its use is the poor characterization of collagen type I, the most abundant protein in bone and skin. In tetrapods collagen type I is a trimer mainly composed of two alpha1 chains and one alpha2 chain, encoded by COL1A1 and COL1A2 genes, respectively. In contrast, in zebrafish three type I collagen genes exist, col1a1a, col1a1b and col1a2 coding for alpha1(I), alpha3(I) and alpha2(I) chains. During embryonic and larval development the three collagen type I genes showed a similar spatio-temporal expression pattern, indicating their co-regulation and interdependence at these stages. In both embryonic and adult tissues, the presence of the three alpha(I) chains was demonstrated, although in embryos alpha1(I) was present in two distinct glycosylated states, suggesting a developmental-specific collagen composition. Even though in adult bone, skin and scales equal amounts of alpha1(I), alpha3(I) and alpha2(I) chains are present, the presented data suggest a tissue-specific stoichiometry and/or post-translational modification status for collagen type I. In conclusion, this data will be useful to properly interpret results and insights gained from zebrafish models of skeletal diseases. PMID- 26876637 TI - Tempo and mode of speciation in Holacanthus angelfishes based on RADseq markers. AB - In this study we estimated the timing of speciation events in a group of angelfishes using 1186 RADseq markers corresponding to 94,880 base pairs. The genus Holacanthus comprises seven species, including two clades of Panama trans Isthmian geminates, which diverged approximately 3-3.5Mya. These clades diversified within the Tropical Eastern Pacific (TEP, three species) and Tropical Western Atlantic (TWA, two species) which our data suggest to have occurred within the past 1.5My in both ocean basins, but may have proceeded via different mechanisms. In the TEP, speciation is likely to have followed a peripatric pathway, while in the TWA, sister species are currently partially sympatric, thus raising the possibility of sympatric speciation. This study highlights the use of RADseq markers for estimating both divergence times and modes of speciation at a 1-3My timescale. PMID- 26876638 TI - A global molecular phylogeny and timescale of evolution for Cryptocercus woodroaches. AB - Cryptocercus is a genus of sub-social wood-feeding cockroaches that represents the sister group to the eusocial termites. We generated mitochondrial (12S+16S rRNA, COII), nuclear (28S rRNA) and Blattbacterium endosymbiont (16S+23S rRNA) sequence data for 8 new Chinese species, and combined these with previously available data to undertake the most extensive analysis of phylogenetic relationships within the genus to date. As expected, phylogenetic relationships among Blattabacterium strains were found to be congruent with those of their hosts. Three major clades were found to exist in Asian populations, one representing taxa from the Hengduan mountains in Southwestern China, a second including taxa from Russia, Korea, Northeastern China, and Yunnan in the Hengduan Mountains, and a third including taxa from the Qinling Mountains and Daba Mountains in Central China. A molecular dating analysis using 7 termite fossils to calibrate the molecular clock indicated that the divergence of American and Asian Cryptocercus occurred 55.09Ma (41.55-72.28Ma 95% CI), and that the radiations of American and Asian taxa occurred 28.48Ma (20.83-37.95Ma 95% CI) and 20.97Ma (15.78-27.21Ma 95% CI) respectively. Reconstruction of ancestral geographic distributions using S-DIVA suggested Cryptocercus was originally distributed across both continents, as opposed to ancestral migration of Cryptocercus from one continent to the other. The last common ancestor of Asian Cryptocercus was inferred to have existed in Central China. An examination of male chromosome numbers in Asian Cryptocercus showed that diploid numbers vary from 2n=15 to 2n=41, and indicates the presence of eight new species. Our study represents the most comprehensive phylogenetic and biogeographic study yet performed for this important group of cockroaches. PMID- 26876639 TI - Peeking through the trapdoor: Historical biogeography of the Aegean endemic spider Cyrtocarenum Ausserer, 1871 with an estimation of mtDNA substitution rates for Mygalomorphae. AB - The Aegean region, located in the Eastern Mediterranean, is an area of rich biodiversity and endemism. Its position, geographical configuration and complex geological history have shaped the diversification history of many animal taxa. Mygalomorph spiders have drawn the attention of researchers, as excellent model systems for phylogeographical investigations. However, phylogeographic studies of spiders in the Aegean region are scarce. In this study, we focused on the phylogeography of the endemic ctenizid trap-door spider Cyrtocarenum Ausserer, 1871. The genus includes two morphologically described species: C. grajum (C.L. Koch, 1836) and C. cunicularium (Olivier, 1811). We sampled 60 specimens from the distributions of both species and analyzed four mitochondrial and two nuclear markers. Cyrtocarenum served as an example to demonstrate the importance of natural history traits in the inference of phylogeographic scenarios. The mtDNA substitution rates inferred for the genus are profoundly higher compared to araneomorph spiders and other arthropods, which seems tightly associated with their biology. We evaluate published mtDNA substitution rates followed in the literature for mygalomorph spiders and discuss potential pitfalls. Following gene tree (maximum likelihood, Bayesian inference) and species tree approaches ((*)BEAST), we reconstructed a time-calibrated phylogeny of the genus. These results, combined with a biogeographical ancestral-area analysis, helped build a biogeographic scenario that describes how the major palaeogeographic and palaeoclimatic events of the Aegean may have affected the distribution of Cyrtocarenum lineages. The diversification of the genus seems to have begun in the Middle Miocene in the present west Aegean area, while major phylogenetic events occurred at the Miocene-Pliocene boundary for C. cunicularium, probably related to the Messinian Salinity Crisis. Our results also demonstrate the clear molecular distinction of the two morphologically described species, but possible cryptic lineages may exist within C. cunicularium. PMID- 26876640 TI - Demographic history and asynchronous spawning shape genetic differentiation among populations of the hard coral Acropora tenuis in Western Australia. AB - Genetic subdivision within populations can ultimately lead to the evolution of new species, and in populations of broadcast-spawners a potential facilitator of genetic subdivision is asynchronous reproduction. However, the factors that shape genetic variation in marine systems are complex and ambiguous, and ecological genetic structure may be influenced by the overriding signature of past demographic events. Here, the relative roles of the timing of reproduction and historical geography on the partitioning of genetic variation were examined in seven populations of the broadcast-spawning coral Acropora tenuis over 12 degrees of latitude. The analysis of multiple loci (mitochondrial control region, two nuclear introns and six microsatellites) revealed significant genetic division between the most northern reef and all other reefs, suggesting that WA reefs were re-colonized from two different sources after the Pleistocene glaciation. Accompanying this pattern was significant genetic differentiation associated with different breeding seasons (spring and autumn), which was greatest in PaxC, in which there were two divergent lineages (PhiST=0.98). This is the second study to find divergent clades of PaxC associated with spring and autumn spawners, strengthening the suggestion of some selective connection to timing of reproduction in corals. This study reiterates the need to incorporate reproductive timing into population genetic studies of corals because it facilitates genetic differentiation; however, careful analysis of population genetic data is required to separate ecological and evolutionary processes. PMID- 26876641 TI - Genetic Improvements in Rice Yield and Concomitant Increases in Radiation- and Nitrogen-Use Efficiency in Middle Reaches of Yangtze River. AB - The yield potential of rice (Oryza sativa L.) has experienced two significant growth periods that coincide with the introduction of semi-dwarfism and the utilization of heterosis. In present study, we determined the annual increase in the grain yield of rice varieties grown from 1936 to 2005 in Middle Reaches of Yangtze River and examined the contributions of RUE (radiation-use efficiency, the conversion efficiency of pre-anthesis intercepted global radiation to biomass) and NUE (nitrogen-use efficiency, the ratio of grain yield to aboveground N accumulation) to these improvements. An examination of the 70-year period showed that the annual gains of 61.9 and 75.3 kg ha(-1) in 2013 and 2014, respectively, corresponded to an annual increase of 1.18 and 1.16% in grain yields, respectively. The improvements in grain yield resulted from increases in the harvest index and biomass, and the sink size (spikelets per panicle) was significantly enlarged because of breeding for larger panicles. Improvements were observed in RUE and NUE through advancements in breeding. Moreover, both RUE and NUE were significantly correlated with the grain yield. Thus, our study suggests that genetic improvements in rice grain yield are associated with increased RUE and NUE. PMID- 26876642 TI - Ion microscopy based on laser-cooled cesium atoms. AB - We demonstrate a prototype of a Focused Ion Beam machine based on the ionization of a laser-cooled cesium beam and adapted for imaging and modifying different surfaces in the few-tens nanometer range. Efficient atomic ionization is obtained by laser promoting ground-state atoms into a target excited Rydberg state, then field-ionizing them in an electric field gradient. The method allows obtaining ion currents up to 130pA. Comparison with the standard direct photo-ionization of the atomic beam shows, in our conditions, a 40-times larger ion yield. Preliminary imaging results at ion energies in the 1-5keV range are obtained with a resolution around 40nm, in the present version of the prototype. Our ion beam is expected to be extremely monochromatic, with an energy spread of the order of the eV, offering great prospects for lithography, imaging and surface analysis. PMID- 26876643 TI - Dissecting the hybridization of oligonucleotides to structured complementary sequences. AB - BACKGROUND: When oligonucleotides hybridize to long target molecules, the process is slowed by the secondary structure in the targets. The phenomenon has been analyzed in several previous studies, but many details remain poorly understood. METHODS: I used a spectrofluorometric strategy, focusing on the formation/breaking of individual base pairs, to study the kinetics of association between a DNA hairpin and >20 complementary oligonucleotides ('antisenses'). RESULTS: Hybridization rates differed by over three orders of magnitude. Association was toehold-mediated, both for antisenses binding to the target's ends and for those designed to interact with the loop. Binding of these latter, besides being consistently slower, was affected to variable, non-uniform extents by the asymmetric loop structure. Divalent metal ions accelerated hybridization, more pronouncedly when nucleation occurred at the loop. Incorporation of locked nucleic acid (LNA) residues in the antisenses substantially improved the kinetics only when LNAs participated to the earliest hybridization steps. The effects of individual LNAs placed along the antisense indicated that the reaction transition state occurred after invading at least the first base pair of the stem. CONCLUSIONS: The experimental approach helps dissect hybridization reactions involving structured nucleic acids. Toehold-dependent, nucleation-invasion models appear fully appropriate for describing such reactions. Estimating the stability of nucleation complexes formed at internal toeholds is the major hurdle for the quantitative prediction of hybridization rates. GENERAL SIGNIFICANCE: While analyzing the mechanisms of a fundamental biochemical process (hybridization), this work also provides suggestions for the improvement of technologies that rely on such process. PMID- 26876645 TI - Interactive mechanism between avian infectious bronchitis S1 protein T cell peptide and avian MHC I molecule. AB - This study aims to construct a 3D structure of the avian major histocompatibility complex (MHC)-beta2M complex through homology modelling technology, perform molecular docking of the predicted infectious bronchitis virus (IBV) S1 protein potential epitope peptide Sp6 (NQFYIKLT) and the avian MHC-beta2M complex, and demonstrate the interactive mechanism between Sp6 and MHC using molecular dynamical simulations. The peptide Sp6 and the non-related peptide NP89-97 (PKKTGGPIY) were used to stimulate in vitro recombinant plasmid (pCAGGS-S1) avian splenic lymphocytes. Flow cytometric results show that CD8(+) T lymphocytes reproduce stimulated by the Sp6 and the nonrelated peptide proliferate by 34.8% and 2.6%, respectively. Meanwhile, fluorescent quantitative PCR results show that the secretion of IFN-gamma in avian splenic lymphocytes increases after Sp6 stimulation. These data suggest that Sp6 can induce the activated avian lymphocytes in vitro to produce CTL, which is the CTL epitope in IBV S1. PMID- 26876644 TI - Evolution and comparative analysis of the bat MHC-I region. AB - Bats are natural hosts to numerous viruses and have ancient origins, having diverged from other eutherian mammals early in evolution. These characteristics place them in an important position to provide insights into the evolution of the mammalian immune system and antiviral immunity. We describe the first detailed partial map of a bat (Pteropus alecto) MHC-I region with comparative analysis of the MHC-I region and genes. The bat MHC-I region is highly condensed, yet relatively conserved in organisation, and is unusual in that MHC-I genes are present within only one of the three highly conserved class I duplication blocks. We hypothesise that MHC-I genes first originated in the beta duplication block, and subsequently duplicated in a step-wise manner across the MHC-I region during mammalian evolution. Furthermore, bat MHC-I genes contain unique insertions within their peptide-binding grooves potentially affecting the peptide repertoire presented to T cells, which may have implications for the ability of bats to control infection without overt disease. PMID- 26876646 TI - Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants. AB - Retrograde signaling can be triggered by changes in organellar gene expression (OGE) induced by inhibitors such as lincomycin (LIN) or mutations that perturb OGE. Thus, an insufficiency of the organelle-targeted prolyl-tRNA synthetase PRORS1 in Arabidopsis thaliana activates retrograde signaling and reduces the expression of nuclear genes for photosynthetic proteins. Recently, we showed that mTERF6, a member of the so-called mitochondrial transcription termination factor (mTERF) family, is involved in the formation of chloroplast (cp) isoleucine-tRNA. To obtain further insights into its functions, co-expression analysis of MTERF6, PRORS1 and two other genes for organellar aminoacyl-tRNA synthetases was conducted. The results suggest a prominent role of mTERF6 in aminoacylation activity, light signaling and seed storage. Analysis of changes in whole-genome transcriptomes in the mterf6-1 mutant showed that levels of nuclear transcripts for cp OGE proteins were particularly affected. Comparison of the mterf6-1 transcriptome with that of prors1-2 showed that reduced aminoacylation of proline (prors1-2) and isoleucine (mterf6-1) tRNAs alters retrograde signaling in similar ways. Database analyses indicate that comparable gene expression changes are provoked by treatment with LIN, norflurazon or high light. A core OGE response module was defined by identifying genes that were differentially expressed under at least four of six conditions relevant to OGE signaling. Based on this module, overexpressors of the Golden2-like transcription factors GLK1 and GLK2 were identified as genomes uncoupled mutants. PMID- 26876647 TI - Extracellular microcystin prediction based on toxigenic Microcystis detection in a eutrophic lake. AB - Existing models for predicting microcystin concentration in water body generally use chlorophyll or cyanobacteria concentration as input variables, although microcystins only originate from toxigenic strains of a few species. Moreover, the nonconcurrency between harmful algal growth and toxin release has yet to be quantified. Therefore, this study explored a new prediction method that considers these toxin production mechanisms for the eutrophic Yangcheng Lake, a large-scale drinking water source in China. The Lake was monitored weekly at six sampling sites from July to October in 2012, including the detection of toxigenic Microcystis (expressed as mcyA copy number) by qPCR. Compared with chlorophyll a, cyanobacteria, and total Microcystis abundance, toxigenic Microcystis concentration was more significant in predicting extracellular microcystin. Site specific nonlinear regression models that link mcyA to microcystins were established. Parameters for toxin release delay (i.e., one or two weeks) were embedded in these models. Further analysis ascribed the different release timescale to NH3-N:TN and TN:TP ratios of approximately 0.015 and 9.2, respectively, which may decrease the delay in microcystin release. Model applications in determining mcyA monitoring frequency and its warning thresholds were discussed. PMID- 26876650 TI - Exercise-induced skeletal muscle signaling pathways and human athletic performance. AB - Skeletal muscle is a highly malleable tissue capable of altering its phenotype in response to external stimuli including exercise. This response is determined by the mode, (endurance- versus resistance-based), volume, intensity and frequency of exercise performed with the magnitude of this response-adaptation the basis for enhanced physical work capacity. However, training-induced adaptations in skeletal muscle are variable and unpredictable between individuals. With the recent application of molecular techniques to exercise biology, there has been a greater understanding of the multiplicity and complexity of cellular networks involved in exercise responses. This review summarizes the molecular and cellular events mediating adaptation processes in skeletal muscle in response to exercise. We discuss established and novel cell signaling proteins mediating key physiological responses associated with enhanced exercise performance and the capacity for reactive oxygen and nitrogen species to modulate training adaptation responses. We also examine the molecular bases underpinning heterogeneous responses to resistance and endurance exercise and the dissociation between molecular 'markers' of training adaptation and subsequent exercise performance. PMID- 26876649 TI - Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage. AB - Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased oxidation with minor changes in the oxidation of key cysteines that may contribute to defective redox signalling in the nerve. PMID- 26876651 TI - Poly(trimethylene carbonate) as a carrier for rifampicin and vancomycin to target therapy-recalcitrant staphylococcal biofilms. AB - Standard antibiotic therapy in osteomyelitis patients is of limited value when methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), or small-colony variants (SCV) are present. Far better results are obtained by local drug delivery of antibiotic combinations including rifampicin, using a suitable carrier. We therefore investigated release kinetics of antibiotics from biodegradable poly(trimethylene carbonate) (PTMC) and in vitro biofilm inhibition of MRSA, MRSE, and S. aureus SCV strains in the course of 24, 72, and 168 h treatment by PTMC, either unloaded, gentamicin-loaded, loaded with rifampicin and fosfomycin, or rifampicin and vancomycin. PTMC appeared to be a suitable carrier for rifampicin alone or in combination with other antibiotics. Biofilm colony forming units and metabolic activity measurement (MTT assay) demonstrated significant (p < 0.05) inhibition for all strains when PTMC loaded with rifampicin and vancomycin was employed, especially after 168 h treatment. Confocal laser scanning microscopy images showed similar qualitative results. PTMC loaded with only gentamicin did not show any inhibition. This exemplifies that PTMC loaded with rifampicin and vancomycin holds promise for the treatment of recalcitrant osteomyelitis. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1828-1837, 2016. PMID- 26876652 TI - A multifunctional polymeric nanofilm with robust chemical performances for special wettability. AB - A multifunctional polymeric nanofilm of a triazinedithiolsilane compound, which can protect metallic substrates and activate the corresponding surface simultaneously, is introduced onto a copper mesh surface via facile solution immersion approaches. The resultant interface exhibits hydrophilic features due to the existence of silanol groups (SiOH) outward and has the potential to act as a superhydrophilic and underwater superoleophobic material. As the polymeric nanofilm atop the copper mesh is modified with long-chain octadecyltrichlorosilane (OTS), the functionalized surface becomes superhydrophobic and superoleophilic. The OTS-modified polymeric nanofilm shows outstanding chemical durability and stability that are seldom concurrently satisfied for a material with special wettability, owing to its inherent architecture. These textures generate high separation efficiency, durable separation capability and excellent thermal stability. The protective ability, originating from the textures of the underlying cross-linked disulfide units (-SS ) and siloxane networks (SiOSi) on the top of the nanofilm, prolongs the chemical durability. The activating capability stemming from the residual SiOH groups improves the chemical stability as a result of the chemical bonds developed by these sites. The significant point of this investigation lies in enlightening us on the fabrication of multifunctional polymeric nanofilms on different metal surfaces using various triazinedithiolsilane compounds, and on the construction of interfaces with controllable wettable performances in demanding research or industrial applications. PMID- 26876653 TI - Impact of marital status on survival of gastric adenocarcinoma patients: Results from the Surveillance Epidemiology and End Results (SEER) Database. AB - Marital status was found to be an independent prognostic factor for survival in various cancer types. In this study, we used the Surveillance, Epidemiology and End Results database to analyze the survival difference among different marital status in the United States. Gastric adenocarcinoma patients from 2004-2012 were enrolled for study. The 5-year cause specific survival (CSS) was our primary endpoint. Totally 29,074 eligible patients were identified. We found that more male patients were married than female. Asian patients had the highest percentages of married than the other races. More married patients were covered by the insurance. Married patients had better 5-year CSS than unmarried, 30.6% vs 25.7%, P < 0.001. The median overall CSS was 17.87 and 13.61 months for the married and unmarried patients, hazard ratio: 1.09 (95% confidence interval: 1.01 1.17), P = 0.027. The survival difference was significant in the insured but not in the uninsured patients. Widowed patients had the worst prognosis compared with other groups even though they had more stage I disease and more well / moderate differentiated tumors. These results indicated that unmarried gastric adenocarcinoma patients were at greater risk of cancer specific mortality. We recommend every patient should have access to best available gastric cancer therapy. PMID- 26876648 TI - Regulation of exercise blood flow: Role of free radicals. AB - During exercise, oxygen and nutrient rich blood must be delivered to the active skeletal muscle, heart, skin, and brain through the complex and highly regulated integration of central and peripheral hemodynamic factors. Indeed, even minor alterations in blood flow to these organs have profound consequences on exercise capacity by modifying the development of fatigue. Therefore, the fine-tuning of blood flow is critical for optimal physical performance. At the level of the peripheral circulation, blood flow is regulated by a balance between the mechanisms responsible for vasodilation and vasoconstriction. Once thought of as toxic by-products of in vivo chemistry, free radicals are now recognized as important signaling molecules that exert potent vasoactive responses that are dependent upon the underlying balance between oxidation-reduction reactions or redox balance. Under normal healthy conditions with low levels of oxidative stress, free radicals promote vasodilation, which is attenuated with exogenous antioxidant administration. Conversely, with advancing age and disease where background oxidative stress is elevated, an exercise-induced increase in free radicals can further shift the redox balance to a pro-oxidant state, impairing vasodilation and attenuating blood flow. Under these conditions, exogenous antioxidants improve vasodilatory capacity and augment blood flow by restoring an "optimal" redox balance. Interestingly, while the active skeletal muscle, heart, skin, and brain all have unique functions during exercise, the mechanisms by which free radicals contribute to the regulation of blood flow is remarkably preserved across each of these varied target organs. PMID- 26876654 TI - Observations of narrow bipolar events reveal how lightning is initiated in thunderstorms. AB - A long-standing but fundamental question in lightning studies concerns how lightning is initiated inside storms, given the absence of physical conductors. The issue has revolved around the question of whether the discharges are initiated solely by conventional dielectric breakdown or involve relativistic runaway electron processes. Here we report observations of a relatively unknown type of discharge, called fast positive breakdown, that is the cause of high power discharges known as narrow bipolar events. The breakdown is found to have a wide range of strengths and is the initiating event of numerous lightning discharges. It appears to be purely dielectric in nature and to consist of a system of positive streamers in a locally intense electric field region. It initiates negative breakdown at the starting location of the streamers, which leads to the ensuing flash. The observations show that many or possibly all lightning flashes are initiated by fast positive breakdown. PMID- 26876655 TI - Screening for and Diagnosis of Depression Among Adolescents in a Large Health Maintenance Organization. AB - OBJECTIVE: The aim of this analysis was to determine changes in patterns of depression screening and diagnosis over three years in primary and specialty mental health care in a large health maintenance organization (HMO) as part of a project to develop quality measures for adolescent depression treatment. METHODS: Two series of aggregate data (2010-2012) were gathered from the electronic health records of the HMO for 44,342 unique adolescents (ages 12 to 21) who had visits in primary and mental health care. Chi square tests assessed the significance of changes in frequency and departmental location of Patient Health Questionnaire-9 (PHQ-9) administration, incidence of depression symptoms, and depression diagnoses. RESULTS: There was a significant increase in PHQ-9 use, predominantly in primary care, consistent with internally generated organizational recommendations to increase screening with the PHQ-9. The increase in PHQ-9 use led to an increase in depression diagnoses in primary care and a shift in the location of some diagnoses from specialty mental health care to primary care. The increase in PHQ-9 use was also linked to a decrease in the proportion of positive PHQ-9 results that led to formal depression diagnoses. CONCLUSIONS: The rate of depression screening in primary care increased over the study period. This increase corresponded to an increase in the number of depression diagnoses made in primary care and a shift in the location in which depression diagnoses were made, from the mental health department to primary care. The frequency of positive PHQ-9 administrations not associated with depression diagnoses also increased. PMID- 26876656 TI - Predictors of Pharmacy-Based Measurement and Self-Report of Antidepressant Adherence: Are Individuals Overestimating Adherence? AB - OBJECTIVE: This study considered various factors as predictors of antidepressant adherence over time as assessed by self-report and medication possession ratios (MPRs) derived from administrative pharmacy data. METHODS: Adherence was assessed at six and 12 months among 443 veterans in ongoing treatment for depression in a trial of peer support. Logistic regression models were utilized to consider predictors of adequate adherence. RESULTS: At six and 12 months, respectively, 36% and 35% of patients had poor adherence on the basis of MPRs and 24% and 18% had poor adherence on the basis of self-report. MPRs indicating poor adherence were more likely among men, members of racial groups other than white, and patients with Hispanic ethnicity. Poor self-reported adherence was associated with increased depressive symptoms and unemployment. CONCLUSIONS: These adherence measures may be complementary. Strategies to improve adherence might target specific demographic groups, unemployed persons, and persons with higher levels of depressive symptoms. PMID- 26876657 TI - Effects of Housing First on Employment and Income of Homeless Individuals: Results of a Randomized Trial. AB - OBJECTIVE: Housing First is emerging as an evidence-based practice for housing and supporting people who are homeless and have a mental illness. The objective of this study was to determine whether Housing First increases the odds of obtaining competitive employment in this population and affects income, including income from informal and illegal sources. METHODS: A total of 2,148 people with a mental illness were recruited from five Canadian cities while they were homeless, classified as having moderate or high needs, and randomly assigned to Housing First or usual care. Housing First participants with high needs received assertive community treatment (ACT), and those with moderate needs received intensive case management (ICM). Every three months, participants were interviewed about employment and earnings in the previous months (median follow up=745 days). Regression models were estimated via generalized estimating equations. RESULTS: ICM recipients had lower odds of obtaining employment compared with the control group with moderate needs. The odds of obtaining employment among ICM recipients increased but their employment rate never exceeded that of the control group. For ACT recipients, the odds of obtaining employment were not significantly different from those of the control group. Among Housing First participants, persons employed at baseline, men, and younger participants had greater odds of employment compared with control participants. Housing First did not appear to significantly increase income. CONCLUSIONS: This was the first large-scale randomized controlled study of Housing First's effects on employment. Further research is needed to determine how Housing First may be enhanced to increase odds of obtaining employment. PMID- 26876659 TI - Use of Modified Positive Behavioral Interventions and Supports in a Psychiatric Inpatient Unit for High-Risk Youths. AB - OBJECTIVE: Despite a call for the reduction and ultimate elimination of the use of seclusion and restraint, research on reduction of these practices in behavioral programs has been limited. This study sought to examine the effectiveness of a modified version of the Positive Behavioral Interventions and Supports (M-PBIS) implemented in a youth psychiatric inpatient unit to reduce use of seclusion and restraint. METHODS: This naturalistic, prospective study covered a four-year period (1,485 admissions). RESULTS: The number of seclusion and restraint events, mean duration of events, and percentage of patients placed in seclusion or restraint were reduced, as was the overall seclusion rate for the unit. Furthermore, there was a significant reduction in the use of pro re nata (PRN) medications for agitation. CONCLUSIONS: These findings suggest that M-PBIS is a promising intervention to use in youth psychiatric inpatient units to reduce seclusion and restraint and PRNs. PMID- 26876658 TI - Therapist- and Client-Level Predictors of Use of Therapy Techniques During Implementation in a Large Public Mental Health System. AB - OBJECTIVE: Many youths receiving community mental health treatment do not receive evidence-based interventions. Research suggests that community mental health therapists use a broad range of therapeutic techniques at low intensities. This study examined the relationship between therapist- and client-level predictors of community-based therapists' report of cognitive, behavioral, psychodynamic, and family techniques within the context of implementation efforts. METHODS: A total of 130 therapists participated from 23 organizations in an urban, publicly funded behavioral health system implementing evidence-based practices. Therapist-level predictors included age, gender, clinical experience, licensure status, and participation in evidence-based practice initiatives. Child-level predictors included therapist-reported child primary disorder (externalizing, internalizing, or other) and child age. Therapists completed the Therapist Procedures Checklist Family Revised, a self-report measure of therapeutic techniques used. RESULTS: Unlicensed therapists were more likely than licensed therapists to report using psychodynamic and behavioral techniques. Therapists who did not participate in an evidence-based practice initiative were less likely to report use of cognitive techniques. Those with clients with externalizing disorders were more likely to report use of behavioral and family techniques. Therapists with the youngest clients (ages three to seven years) were most likely to report use of behavioral techniques and less likely to report use of cognitive and psychodynamic techniques. CONCLUSIONS: Results suggest that both therapist and client factors predict self-reported use of therapy techniques. Participating in an evidence based practice initiative was associated with increased reports of using cognitive techniques. Therapists reported using behavioral and family techniques more than other techniques when working with youths with externalizing disorders and using fewer cognitive and psychodynamic techniques with young clients. PMID- 26876660 TI - Effects of Clinical Decision Topic on Patients' Involvement in and Satisfaction With Decisions and Their Subsequent Implementation. AB - OBJECTIVE: Clinical decision making is an important aspect of mental health care. Predictors of how patients experience decision making and whether decisions are implemented are underresearched. This study investigated the relationship between decision topic and involvement in the decision, satisfaction with it, and its subsequent implementation from both staff and patient perspectives. METHODS: As part of the Clinical Decision Making and Outcome in Routine Care for People With Severe Mental Illness study, patients (N=588) and their providers (N=213) were recruited from community-based mental health services in six European countries. Both completed bimonthly assessments for one year using the Clinical Decision Making in Routine Care Scale to assess the decision topic and implementation; both also completed the Clinical Decision Making Involvement and Satisfaction Scale. RESULTS: Three categories of decision topics were determined: treatment (most frequently cited), social, and financial. The topic identified as most important remained stable over the follow-up. Patients were more likely to rate their involvement as active rather than passive for social decisions (odds ratio [OR]=5.7, p<.001) and financial decisions (OR=9.5, p<.001). They were more likely to report higher levels of satisfaction rather than lower levels for social decisions (OR=1.5, p=.01) and financial decisions (OR=1.7, p=.01). Social decisions were more likely to be partly implemented (OR=3.0, p<.001) or fully implemented (OR=1.7, p=.03) than not implemented. CONCLUSIONS: Patients reported poorer involvement, satisfaction, and implementation in regard to treatment related decisions, compared with social and financial decisions. Clinicians may need to employ different interactional styles for different types of decisions to maximize satisfaction and decision implementation. PMID- 26876661 TI - Trajectories of Recovery Among Formerly Homeless Adults With Serious Mental Illness. AB - OBJECTIVE: Recovery from mental illness is possible, but individuals with co occurring disorders and homelessness face challenges. Although a nonlinear recovery course is assumed, few studies have analyzed recovery over time. This mixed-methods study examined recovery trajectories over 18 months after enrollment in supportive housing programs of 38 participants with DSM axis I diagnoses. METHODS: Qualitative interview data were quantified through consensual ratings to generate a recovery score for four waves of data collection based on eight recovery domains culled from the literature. Case study analyses were conducted of participants whose scores varied by one standard deviation or more between baseline and 18 months to identify which domains were important. RESULTS: Most of the 38 participants (N=23) had no significant change in recovery; seven had a negative trajectory, and eight had a positive trajectory. Case studies of these 15 participants indicated domains that contributed to change: significant other relationships (N=9), engagement in meaningful activities (N=9), mental health (N=7), family relationships (N=6), general medical health (N=5), housing satisfaction (N=5), employment (N=2), and substance use (N=1). Except for mental health and substance use (which contributed only to negative trajectories), the influence of domains was both positive and negative. Domains were intertwined; for example, variation in relationships was linked to changes in meaningful activities. CONCLUSIONS: This study showed little change in recovery over time for most participants and a decline in mental health for a small minority. Findings underscore the importance of social relationships and meaningful activities among individuals with serious mental illness, who experience complex challenges. PMID- 26876662 TI - Attitudes Toward Mental Health Help Seeking as Predictors of Future Help-Seeking Behavior and Use of Mental Health Treatments. AB - OBJECTIVES: The study examined the association of attitudes toward mental health help seeking and beliefs about the effectiveness of treatments with future help seeking behavior and use of specific services in the general population. METHODS: Data on attitudes and beliefs at baseline were taken from the U.S. National Comorbidity Survey (NCS), a general population survey conducted in 1990-1992. Help seeking from various providers and use of psychiatric medications and counseling or therapy were examined in the NCS follow-up, in which 5,001 of the original NCS participants were reinterviewed in 2001-2003. RESULTS: Willingness to seek professional help for a serious emotional problem and feeling comfortable talking about personal problems with professionals were significantly associated with future help seeking and treatment use. One-third (33.4%) of participants who stated at baseline that they would "definitely go" to a professional if they had a serious emotional problem sought future help, compared with 20.7% of those who would "definitely not go." Corresponding values were 33.4% and 24.4% for those who reported feeling "very comfortable" and "not at all comfortable," respectively, talking about personal problems with a professional. The associations were consistent among participants with and without a history of help seeking and with and without mood, anxiety, or substance use disorders during the follow-up. Embarrassment if friends found out and beliefs about treatment effectiveness were not associated with future help seeking or service use. CONCLUSIONS: Identification of attitudinal factors most closely linked to future mental health help seeking has potential implications for public mental health campaigns. PMID- 26876664 TI - Use of ICD-9-CM Diagnosis Code V62.89 (Other Psychological or Physical Stress, Not Elsewhere Classified) Following a Suicide Attempt. AB - OBJECTIVE: This study examined the demographic, diagnostic, and service characteristics of veterans who received services for "other psychological or physical stress, not elsewhere classified" (ICD-9-CM V62.89) in the month following a suicide attempt. METHODS: An electronic search of a Veterans Health Administration (VHA) suicide event reporting system identified 22,701 veterans who were survivors of a suicide attempt. Their clinical service encounter records were extracted from a VHA administrative database to identify those who received services related to V62.89. RESULTS: Services related to V62.89 were provided to N=2,173 (9.6%) of the sample. Chaplains were the predominant service provider, identified in N=1,745 (80%) of the service encounters. Differences were noted between those who received services related to V62.89 from a chaplain or from another service provider. CONCLUSIONS: V62.89 appears to be a focus of clinical concern for some veteran suicide attempt survivors. Additional research is needed to better understand any implications for suicide "postvention." PMID- 26876663 TI - Behavioral Health Services in the Changing Landscape of Private Health Plans. AB - OBJECTIVE: Health plans play a key role in facilitating improvements in population health and may engage in activities that have an impact on access, cost, and quality of behavioral health care. Although behavioral health care is becoming more integrated with general medical care, its delivery system has unique aspects. The study examined how health plans deliver and manage behavioral health care in the context of the Affordable Care Act (ACA) and the 2008 Mental Health Parity and Addiction Equity Act (MHPAEA). This is a critical time to examine how health plans manage behavioral health care. METHODS: A nationally representative survey of private health plans (weighted N=8,431 products; 89% response rate) was conducted in 2010 during the first year of MHPAEA, when plans were subject to the law but before final regulations, and just before the ACA went into effect. The survey addressed behavioral health coverage, cost-sharing, contracting arrangements, medical home innovations, support for technology, and financial incentives to improve behavioral health care. RESULTS: Coverage for inpatient and outpatient behavioral health services was stable between 2003 and 2010. In 2010, health plans were more likely than in 2003 to manage behavioral health care through internal arrangements and to contract for other services. Medical home initiatives were common and almost always included behavioral health, but financial incentives did not. Some plans facilitated providers' use of technology to improve care delivery, but this was not the norm. CONCLUSIONS: Health plans are key to mainstreaming and supporting delivery of high-quality behavioral health services. Since 2003, plans have made changes to support delivery of behavioral health services in the context of a rapidly changing environment. PMID- 26876665 TI - Generalizability of the NAMI Family-to-Family Education Program: Evidence From an Efficacy Study. AB - Previous studies conducted in Maryland of the Family-to-Family (FTF) education program of the National Alliance on Mental Illness (NAMI) found that FTF reduced subjective burden and distress and improved empowerment, mental health knowledge, self-care, and family functioning, establishing it as an evidence-based practice. In the study reported here, the FTF program of NAMI-NYC Metro was evaluated. Participants (N=83) completed assessments at baseline and at completion of FTF. Participants had improved family empowerment, family functioning, engagement in self-care activities, self-perception of mental health knowledge, and emotional acceptance as a form of coping. Scores for emotional support and positive reframing also improved significantly. Displeasure in caring for the family member, a measure of subjective burden, significantly declined. Despite the lack of a control group and the limited sample size, this study further supports the efficacy of FTF with a diverse urban population. PMID- 26876666 TI - From the mountains to the coast and back again: Ancient biogeography in a radiation of short-range endemic harvestmen from California. AB - The harvestmen genus Calicina is represented by 25 short-range endemic species occurring in the western Sierra Nevada, Transverse and Coast Ranges of California. Our principal aim was to reconstruct the temporal and spatial biogeographic history of this arachnid lineage. We inferred a time-calibrated species tree for 21 of 25 described Calicina species using multiple genes and multilocus coalescent-based methods. This species tree was used as a framework for algorithmic biogeographic and divergence time analyses, and a phylogenetic canonical correlation analysis (CCA) was used to examine the relationship between morphological evolution and environmental variables. Species tree and biogeographic analyses indicate that high-elevation Sierran taxa are early diverging in Calicina, with subsequent biogeographic "criss-crossing" of lineages from the Sierra Nevada to the Coast Ranges, back to the Sierra Nevada, then back to Coast Ranges. In both the Sierra Nevada and Coast Ranges, distantly-related parapatric lineages essentially never occur in sympatry. CCA reveals that in both the Coast Ranges and the Sierra Nevada, distant phylogenetic relatives evolve convergent morphologies. Our evidence shows that Calicina is clearly dispersal limited, with an ancient biogeographic history that provides unique insight into the complex geologic evolution of California since the mid-Paleogene. PMID- 26876667 TI - Oncometabolic Nuclear Reprogramming of Cancer Stemness. AB - By impairing histone demethylation and locking cells into a reprogramming-prone state, oncometabolites can partially mimic the process of induced pluripotent stem cell generation. Using a systems biology approach, combining mathematical modeling, computation, and proof-of-concept studies with live cells, we found that an oncometabolite-driven pathological version of nuclear reprogramming increases the speed and efficiency of dedifferentiating committed epithelial cells into stem-like states with only a minimal core of stemness transcription factors. Our biomathematical model, which introduces nucleosome modification and epigenetic regulation of cell differentiation genes to account for the direct effects of oncometabolites on nuclear reprogramming, demonstrates that oncometabolites markedly lower the "energy barriers" separating non-stem and stem cell attractors, diminishes the average time of nuclear reprogramming, and increases the size of the basin of attraction of the macrostate occupied by stem cells. These findings establish the concept of oncometabolic nuclear reprogramming of stemness as a bona fide metabolo-epigenetic mechanism for generation of cancer stem-like cells. PMID- 26876668 TI - Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia. AB - Patients with an HNF1B(S148L/+) mutation (MODY5) typically exhibit pancreatic hypoplasia. However, the molecular mechanisms are unknown due to inaccessibility of patient material and because mouse models do not fully recapitulate MODY5. Here, we differentiated MODY5 human-induced pluripotent stem cells (hiPSCs) into pancreatic progenitors, and show that the HNF1B(S148L/+) mutation causes a compensatory increase in several pancreatic transcription factors, and surprisingly, a decrease in PAX6 pancreatic gene expression. The lack of suppression of PDX1, PTF1A, GATA4, and GATA6 indicates that MODY5-mediated pancreatic hypoplasia is mechanistically independent. Overexpression studies demonstrate that a compensatory increase in PDX1 gene expression is due to mutant HNF1B(S148L/+) but not wild-type HNF1B or HNF1A. Furthermore, HNF1B does not appear to directly regulate PAX6 gene expression necessary for glucose tolerance. Our results demonstrate compensatory mechanisms in the pancreatic transcription factor network due to mutant HNF1B(S148L/+) protein. Thus, patients typically develop MODY5 but not neonatal diabetes despite exhibiting pancreatic hypoplasia. PMID- 26876670 TI - Optimal architectures for long distance quantum communication. AB - Despite the tremendous progress of quantum cryptography, efficient quantum communication over long distances (>= 1000 km) remains an outstanding challenge due to fiber attenuation and operation errors accumulated over the entire communication distance. Quantum repeaters (QRs), as a promising approach, can overcome both photon loss and operation errors, and hence significantly speedup the communication rate. Depending on the methods used to correct loss and operation errors, all the proposed QR schemes can be classified into three categories (generations). Here we present the first systematic comparison of three generations of quantum repeaters by evaluating the cost of both temporal and physical resources, and identify the optimized quantum repeater architecture for a given set of experimental parameters for use in quantum key distribution. Our work provides a roadmap for the experimental realizations of highly efficient quantum networks over transcontinental distances. PMID- 26876669 TI - MicroRNAs for Fine-Tuning of Mouse Embryonic Stem Cell Fate Decision through Regulation of TGF-beta Signaling. AB - Over the past years, microRNAs (miRNAs) have emerged as crucial factors that regulate self-renewal and differentiation of embryonic stem cells (ESCs). Although much is known about their role in maintaining ESC pluripotency, the mechanisms by which they affect cell fate decisions remain poorly understood. By performing deep sequencing to profile miRNA expression in mouse ESCs (mESCs) and differentiated embryoid bodies (EBs), we identified four differentially expressed miRNAs. Among them, miR-191 and miR-16-1 are highly expressed in ESCs and repress Smad2, the most essential mediator of Activin-Nodal signaling, resulting in the inhibition of mesendoderm formation. miR-23a, which is also down-regulated in the differentiated state, suppresses differentiation toward the endoderm and ectoderm lineages. We further identified miR-421 as a differentiation-associated regulator through the direct repression of the core pluripotency transcription factor Oct4 and the bone morphogenetic protein (BMP)-signaling components, Smad5 and Id2. Collectively, our findings uncover a regulatory network between the studied miRNAs and both branches of TGF-beta/BMP-signaling pathways, revealing their importance for ESC lineage decisions. PMID- 26876671 TI - Spatially resolved optical absorption spectroscopy of single- and few-layer MoS2 by hyperspectral imaging. AB - The possibility of spatially resolving the optical properties of atomically thin materials is especially appealing as they can be modulated at the micro- and nanoscale by reducing their thickness, changing the doping level or applying a mechanical deformation. Therefore, optical spectroscopy techniques with high spatial resolution are necessary to get a deeper insight into the properties of two-dimensional (2D) materials. Here we study the optical absorption of single- and few-layer molybdenum disulfide (MoS2) in the spectral range from 1.24 eV to 3.22 eV (385 nm to 1000 nm) by developing a hyperspectral imaging technique that allows one to probe the optical properties with diffraction limited spatial resolution. We find hyperspectral imaging very suited to study indirect bandgap semiconductors, unlike photoluminescence which only provides high luminescence yield for direct gap semiconductors. Moreover, this work opens the door to study the spatial variation of the optical properties of other 2D systems, including non-semiconducting materials where scanning photoluminescence cannot be employed. PMID- 26876673 TI - Double emulsions for the compatibilization of hydrophilic nanocellulose with non polar polymers and validation in the synthesis of composite fibers. AB - A route for the compatibilization of aqueous dispersions of cellulose nanofibrils (CNFs) with a non-polar polymer matrix is proposed to overcome a major challenge in CNF-based material synthesis. Non-ionic surfactants were used in CNF aqueous dispersions equilibrated with an organic phase (for demonstration, a polystyrene solution, PS, was used). Stable water-in-oil-in-water (W/O/W) double emulsions were produced as a result of the compromise between composition and formulation variables. Most remarkably, the proposed route for CNF integration with hydrophobic polymers removed the need for drying or solvent-exchange of the CNF aqueous dispersion prior to processing. The rheological behavior of the double emulsions showed strong shear thinning behavior and facilitated CNF-PS co-mixing in solid nanofibers upon electrospinning. The morphology and thermal properties of the resultant nanofibers revealed that CNFs were efficiently integrated in the hydrophobic matrix which was consistent with the high interfacial area of the precursor double emulsion. In addition, the morphology and quality of the composite nanofibers can be controlled by the conductivity (ionic strength) of the CNF dispersion. Overall, double emulsion systems are proposed as a novel, efficient and scalable platform for CNF co-processing with non-polar systems and they open up the possibility for the redispersion of CNFs after removal of the organic phase. PMID- 26876672 TI - Cyclin-dependent kinase 2 protects podocytes from apoptosis. AB - Loss of podocytes is an early feature of diabetic nephropathy (DN) and predicts its progression. We found that treatment of podocytes with sera from normoalbuminuric type 1 diabetes patients with high lipopolysaccharide (LPS) activity, known to predict progression of DN, downregulated CDK2 (cyclin dependent kinase 2). LPS-treatment of mice also reduced CDK2 expression. LPS induced downregulation of CDK2 was prevented in vitro and in vivo by inhibiting the Toll-like receptor (TLR) pathway using immunomodulatory agent GIT27. We also observed that CDK2 is downregulated in the glomeruli of obese Zucker rats before the onset of proteinuria. Knockdown of CDK2, or inhibiting its activity with roscovitine in podocytes increased apoptosis. CDK2 knockdown also reduced expression of PDK1, an activator of the cell survival kinase Akt, and reduced Akt phosphorylation. This suggests that CDK2 regulates the activity of the cell survival pathway via PDK1. Furthermore, PDK1 knockdown reduced the expression of CDK2 suggesting a regulatory loop between CDK2 and PDK1. Collectively, our data show that CDK2 protects podocytes from apoptosis and that reduced expression of CDK2 associates with the development of DN. Preventing downregulation of CDK2 by blocking the TLR pathway with GIT27 may provide a means to prevent podocyte apoptosis and progression of DN. PMID- 26876674 TI - Production of Diacylglycerol-enriched Oil by Glycerolysis of Soybean Oil using a Bubble Column Reactor in a Solvent-free System. AB - In this study, diacylglycerol-enriched soybean oil (DESO) was synthesized through Lipozyme 435-catalyzed glycerolysis of soybean oil (SO) in a solvent-free system using a modified bubble column reactor. The effects of enzyme load, mole ratio of glycerol to soybean oil, reaction temperature, gas flow and reaction time on DAG production were investigated. The selected conditions were established as being enzyme load of 4 wt% (mass of substrates), glycerol/soybean oil mole ratio of 20:1, reaction temperature of 80 degrees C, gas flow of 10.6 cm/min, and a reaction time of 2.5 h, obtaining the DAG content of 49.4+/-0.5 wt%. The reusability of Lipozyme 435 was evaluated by monitoring the contents of DAG, monoacylglycerol (MAG) and triacylglycerol (TAG) in 10 consecutive runs. After purified by one-step molecular distillation, the DAG content of 63.5+/-0.3 wt% was achieved in DESO. The mole ratio of 1, 3-DAG to 1, 2-DAG was 2:1 and the fatty acid composition had no significant difference from that of soybean oil. However, the thermal properties of DESO and SO had considerable differences. Polymorphic form of DESO were mainly the beta form and minor amounts of the beta' form. Granular aggregation and round-shaped crystals were detected in DESO. PMID- 26876675 TI - Dietary Effects of Oxidized Eicosapentaenoic Acid (EPA) and Intact EPA on Hepatic Steatosis Induced by a High-sucrose Diet and Liver-X-receptor alpha Agonist in Mice. AB - Numerous studies have shown that dietary omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA), improve lipid metabolism. The beneficial effects of PUFA-derived oxidation products have been increasingly reported. However, EPA is easily oxidized in food products and in the human body, generating various derivatives of oxidized EPA (oxEPA), such that these oxidation products may partially contribute to EPA's effect. We previously reported that oxEPA was more potent than intact EPA in reducing liver-X-receptor alpha (LXRalpha)-induced cellular triacylglycerol (TG) accumulation. However, the in vivo hypolipidemic effects of oxEPA remain unclear. In the present study, we evaluated the effect of oral administration of EPA and oxEPA on hepatic steatosis in mice induced by a high-sucrose diet and a synthetic LXRalpha agonist, TO 901317. Both EPA and oxEPA reduced TG accumulation in the liver and plasma biomarkers of liver injury. Furthermore, they suppressed the expression of lipogenic genes, but not beta-oxidation genes, in a similar pattern as the biomarkers. Our results suggest that oxEPA and intact EPA suppress de novo lipogenesis to ameliorate hepatic steatosis. PMID- 26876676 TI - Unexpected Irregular Monoterpene "Yomogi Alcohol" in the Volatiles of the Lathyrus L. species (Leguminosae) of Cyprus. AB - Lathyrus species including L. ochrus and L. sativus are known for their food, feed and horticultural uses. Despite their widespread uses and cultivation, there is limited information on their chemistry. Previously, only the essential oil composition of L. rotundifolius, L. vernus and volatiles of L. odoratus have been reported. In the present research, volatiles of seven Lathyrus L. species, namely, L. aphaca, L. ochrus, L. cicera, L. sativus, L. gorgonei, L. saxatilis and L. blepharicarpos var. cyprius were analyzed by SPME GC-MS for the first time. Plant materials were collected from five different locations in Cyprus (February-March 2012). The main components of L. aphaca volatiles from four locations were yomogi alcohol 26.1-16.5%, camphor 21.6-10.1%, tetradecane 14.3 0%; L. cicera from five locations were yomogi alcohol 20.3-3.0%, camphor 18.7 2.0%; L. gorgonei from two locations were yomogi alcohol 24.5-13.1%, camphor 17.1 9.0% and L. sativus was yomogi alcohol 11.4%, camphor 9.0%. Yomogi alcohol was not present as the major compound in L. ochrus (2-methyl butanoic acid 7.2%), L. saxatilis (hexanal 7.7%) and L. blepharicarpos var. cyprius ((Z)-3-hexenal 8.6%) volatiles. The volatiles of the Lathyrus species were also compared with each other quantitative and qualitatively using AHC analysis to find out differences among the species. The irregular monoterpene yomogi alcohol is reported from the Lathyrus and the Leguminosae family for the first time. The existence of yomogi alcohol in Lathyrus volatiles points out that the irregular monoterpenes are not restricted solely to Asteraceae family. PMID- 26876677 TI - Synthesis and Characterization of Dioctanoyl Glycerate as Water-soluble Trypsin Inhibitor. AB - Glyceric acids (GAs) esterified with long acyl chains (> C16) exhibit antitrypsin activity (Folia Microbiol. 46, 21-23 (2001)). However, their hydrophobic nature, derived from the long acyl chains, has limited the number of studies on their physical and biological properties. To improve the water solubility of diacyl GAs, GA was esterified with octanoyl groups (C8), and its physical properties were investigated. Synthesized dioctanoyl GA was not water-soluble, whereas its sodium salt was. Surface tension measurements of dioctanoyl GA sodium salt (diC8GA-Na) in water revealed that the critical micelle concentration (CMC) was 0.82 mM, and surface tension at the CMC was 25.5 mN/m. Additionally, diC8GA-Na inhibited casein digestion by trypsin to a greater extent than dioleoyl GA. These data suggest that water-soluble diacyl GAs may have utility as surfactants and bioactive compounds. PMID- 26876678 TI - Enhancement of Biodegradable Plastic-degrading Enzyme Production from Paraphoma like Fungus, Strain B47-9. AB - To improve the productivity of Paraphoma-like fungal strain B47-9 for biodegradable plastic (BP)-degrading enzyme (PCLE), the optimal concentration of emulsified poly(butylene succinate-co-adipate) (PBSA) in the medium was determined. Emulsified PBSA was consumed as a sole carbon source and an inducer of PCLE production by strain B47-9. Among the various concentrations of emulsified PBSA [0.09-0.9% (w/v)] used in flask cultivation, 0.27% yielded the maximum enzyme activity within a short cultivation period. To evaluate the residual concentration of emulsified PBSA in culture, emulsified PBSA in aliquots of culture supernatant was digested in vitro, and the concentration of released monomerised succinic acid was determined. Regardless of the initial concentration of emulsified PBSA in medium, PCLE activity was detected after residual succinic acid decreased below 0.04 mg/mL in culture broth. Jarfermentation was performed at a 0.27% PBSA concentration. Among the various airflow rates tested, 1 LPM resulted in a PCLE production rate of 1.0 U/mL/day. The enzyme activity in the resulting culture filtrate (4.2 U/2 mL) was shown to degrade commercial BP films (1 * 1 cm, 20 um thickness) within 8 hours. PMID- 26876679 TI - Erythrocyte Membrane Fatty Acid Composition in Premenopausal Patients with Iron Deficiency Anemia. AB - Iron deficiency anemia (IDA) is one of the most common nutritional disorders in the world. In the present study, we evaluated erythrocyte membrane fatty acid composition in premenopausal patients with IDA. Blood samples of 102 premenopausal women and 88 healthy control subjects were collected. After the erythrocytes were separated from the blood samples, the membrane lipids were carefully extracted, and the various membrane fatty acids were measured by gas chromatography (GC). Statistical analyses were performed with the SPSS software program. We used blood ferritin concentration <15 ng/mL as cut-off for the diagnosis of IDA. The five most abundant individual fatty acids obtained were palmitic acid (16:0), oleic acid (18:1, n-9c), linoleic acid (18:2, n-6c), stearic acid (18:0), and erucic acid (C22:1, n-9c). These compounds constituted about 87% of the total membrane fatty acids in patients with IDA, and 79% of the total membrane fatty acids in the control group. Compared with control subjects, case patients had higher percentages of palmitic acid (29.9% case versus 25.3% control), oleic acid (16.8% case versus 15.1% control), and stearic acid (13.5% case versus 10.5% control), and lower percentages of erucic acid (11.5% case versus 13.6% control) and linoleic acid (15.2% case versus 15.4% control) in their erythrocyte membranes. In conclusion, the total-erythrocyte-membrane saturated fatty acid (SFA) composition in premenopausal women with IDA was found to be higher than that in the control group; however, the total-erythrocyte membrane unsaturated fatty acid (UFA) composition in premenopausal women with IDA was found to be lower than that in the control group. The differences in these values were statistically significant. PMID- 26876680 TI - Preparation and Properties of Nonionic Vesicles Prepared with Polyglycerol Fatty Acid Esters Using the Supercritical Carbon Dioxide Reverse Phase Evaporation Method. AB - Previously, we reported a new preparation method for liposomes and niosomes (nonionic vesicles) using supercritical carbon dioxide (scCO2) as the solvent (scRPE method). In this study, niosomes were prepared from polyglycerol fatty acid ester (PG ester)-type nonionic surfactants. These surfactants are made from naturally derived materials and are neither harmful to the human body nor to the environment. Niosomes were prepared using the scRPE method with ethanol as the co solvent. Through this method, decaglycerol distearate (DG2S) and decaglycerol diisostearate (DG2IS) formed niosomes. On the other hand, decaglycerol monostearate (DG1S), which has a high hydrophilic-lipophilic balance (HLB) value, yielded a solution of spherical micelles, and decaglycerol tristearate (DG3S), which has a low HLB value, yielded a gel-like solution. Niosomes of DG2IS had higher trapping efficiencies and dispersion stabilities than those of DG2S because the membrane fluidity of the DG2IS niosomes was greater than that of the DG2S niosomes. The niosomes obtained in the present study are candidates for cosmetic and pharmaceutical applications because they are formed from nonionic surfactants derived from natural sources, and prepared using the scRPE method, which avoids the use of harmful organic solvents. PMID- 26876681 TI - Immunomodulatory Effectiveness of Fish Oil and omega-3 Fatty Acids in Human Non melanoma Skin Carcinoma Cells. AB - Fish oil is composed of various fatty acids among which omega-3 fatty acids are considered as most beneficial. The effects of fish oil on the activity of a topical anticancer drug, imiquimod, and the immunomodulatory activity of omega-3 fatty acids was investigated in human basal and squamous cell carcinoma cell lines. Imiquimod-fish oil mixture exhibited higher carcinoma cell growth inhibition and immunomodulatory activity than imiquimod alone, especially against squamous cell carcinoma cells. Omega-3 fatty acids exhibited growth inhibition of both basal cell and squamous cell carcinoma cell lines and modulated the immune response. Omega-3 fatty acids of fish oil serve as inducers of interleukin-10, an anti-inflammatory cytokine, and as suppressors of interleukin-6 and tumor necrosis factor-alpha, which not only depress tumor growth but also adequately control the inflammatory side effects of imiquimod. Thus, imiquimod administration with fish oil could be beneficial for inhibition of non-melanoma skin carcinoma cells but further in vivo studies are needed to understand their role in skin cancer. PMID- 26876682 TI - ALA-PDT elicits oxidative damage and apoptosis in UVB-induced premature senescence of human skin fibroblasts. AB - BACKGROUND: 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts. METHODS: We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635nm wavelength (50mW/cm(2)). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit 8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining. RESULTS: Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00mmol/L ALA for 6h (P<0.05). Compared with control group, intracellular ROS level, MMP, and apoptotic rate were increased (P<0.05) and proliferative activity was decreased (P<0.05) in UVB-SIPS-HDFs treated with ALA-PDT, which were positively correlated to ALA incubation time and red light laser dose. CONCLUSION: Our study demonstrated that ALA-PDT elicits oxidative damage and apoptosis in photoaged fibroblasts in vitro, which may be the basis for the rejuvenating effects on photoaged skin. PMID- 26876683 TI - The prevalence and characteristics of hallucinations, delusions and minor phenomena in a non-demented population sample aged 60 years and over. AB - OBJECTIVE: Psychotic phenomena can occur in non-clinical subjects. The goals of this study were to assess the prevalence of delusions, hallucinations and minor 'psychotic' phenomena (visual illusions, feeling of presence and passage hallucinations) and to describe the characteristics of the latter in a non clinical older population. METHODS: Three hundred and thirteen individuals aged 60 years and older, without cognitive deficits (according to mini-mental state examination scores) or patent psychotic disease, answered a structured questionnaire focusing on delusions, hallucinations and minor phenomena that they had experienced in the previous month. The study sample was stratified by age and gender according to French demographic characteristics. RESULTS: Twenty per cent of participants reported one or more psychotic phenomena. These subjects did not differ from those without psychotic symptoms as regards their age, mini-mental state examination scores or education. Minor phenomena were the most common (13%). Hallucinations, in any sensory modality, occurred in 9% of participants. No verbal auditory hallucinations or delusions were reported. The prevalence of minor phenomena increased with age and was associated with the use of psychoactive drugs. CONCLUSION: By extending the spectrum of psychotic symptoms to minor phenomena, we found that psychotic symptoms were common in a non clinical older population. Whether the increasing prevalence of minor phenomena with age is due to prodromal neurodegenerative disease or to other factors remains to be investigated. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876684 TI - Arsenic Metabolites, Including N-Acetyl-4-hydroxy-m-arsanilic Acid, in Chicken Litter from a Roxarsone-Feeding Study Involving 1600 Chickens. AB - The poultry industry has used organoarsenicals, such as 3-nitro-4 hydroxyphenylarsonic acid (Roxarsone, ROX), to prevent disease and to promote growth. Although previous studies have analyzed arsenic species in chicken litter after composting or after application to agricultural lands, it is not clear what arsenic species were excreted by chickens before biotransformation of arsenic species during composting. We describe here the identification and quantitation of arsenic species in chicken litter repeatedly collected on days 14, 24, 28, 30, and 35 of a Roxarsone-feeding study involving 1600 chickens of two strains. High performance liquid chromatography separation with simultaneous detection by both inductively coupled plasma mass spectrometry and electrospray ionization tandem mass spectrometry provided complementary information necessary for the identification and quantitation of arsenic species. A new metabolite, N-acetyl-4 hydroxy-m-arsanilic acid (N-AHAA), was identified, and it accounted for 3-12% of total arsenic. Speciation analyses of litter samples collected from ROX-fed chickens on days 14, 24, 28, 30, and 35 showed the presence of N-AHAA, 3-amino-4 hydroxyphenylarsonic acid (3-AHPAA), inorganic arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), and ROX. 3-AHPAA accounted for 3-19% of the total arsenic. Inorganic arsenicals (the sum of As(III) and As(V)) comprised 2-6% (mean 3.5%) of total arsenic. Our results on the detection of inorganic arsenicals, methylarsenicals, 3-AHPAA, and N-AHAA in the chicken litter support recent findings that ROX is actually metabolized by the chicken or its gut microbiome. The presence of the toxic metabolites in chicken litter is environmentally relevant as chicken litter is commonly used as fertilizer. PMID- 26876686 TI - Light-Regulated Molecular Trafficking in a Synthetic Water-Soluble Host. AB - Cucurbit[8]uril (CB[8])-mediated complexation of a dicationic azobenzene in water allows for the light-controlled encapsulation of a variety of second guest compounds, including amino acids, dyes, and fragrance molecules. Such controlled guest sequestration inside the cavity of CB[8] enables the regulation of the thermally induced phase transition of poly(N-isopropylacrylamide)-which is not photosensitive-thus demonstrating the robustness and relevancy of the light regulated CB[8] complexation. PMID- 26876685 TI - An Ultra-thin Amniotic Membrane as Carrier in Corneal Epithelium Tissue Engineering. AB - Amniotic membranes (AMs) are widely used as a corneal epithelial tissue carrier in reconstruction surgery. However, the engineered tissue transparency is low due to the translucent thick underlying AM stroma. To overcome this drawback, we developed an ultra-thin AM (UAM) by using collagenase IV to strip away from the epithelial denuded AM (DAM) some of the stroma. By thinning the stroma to about 30 MUm, its moist and dry forms were rendered acellular, optically clear and its collagen framework became compacted and inerratic. Engineered rabbit corneal epithelial cell (RCEC) sheets generated through expansion of limbal epithelial cells on UAM were more transparent and thicker than those expanded on DAM. Moreover, DeltaNp63 and ABCG2 gene expression was greater in tissue engineered cell sheets expanded on UAM than on DAM. Furthermore, 2 weeks after surgery, the cornea grafted with UAM based cell sheets showed higher transparency and more stratified epithelium than the cornea grafted with DAM based cell sheets. Taken together, tissue engineered corneal epithelium generated on UAM has a preferable outcome because the transplanted tissue is more transparent and better resembles the phenotype of the native tissue than that obtained by using DAM for this procedure. UAM preserves compact layer of the amniotic membrane and maybe an ideal substrate for corneal epithelial tissue engineering. PMID- 26876689 TI - Current control by electrode coatings formed by polymerization of dopamine at prussian blue-modified electrodes. AB - Electrode coating with polydopamine (PDA) is fast becoming a popular surface modification technique. In this study we report the investigation of the use of PDA as electrode coatings with Prussian blue (PB) as an electrode material model. The PB layer was galvanostatically deposited at an Au electrode, followed by PDA coating with the assistance of ammonium persulfate as an oxidant. The thickness of PDA coatings was measured to be ~60 nm. Electrochemical characterization of the PDA-coated PB electrode revealed that the PDA coatings could stabilize the PB at neutral pH and allow the permeation of hydrogen peroxide (H2O2). Moreover, the PDA coatings were found to effectively exclude the common interfering compounds such as cysteine, ascorbic acid and uric acid, and exhibit selective electrocatalysis towards the electroreduction of H2O2. Accordingly, the PDA coated PB electrode was applied for determination of H2O2 released from live cells. PMID- 26876688 TI - Comparison between two-dimensional and three-dimensional quantitative coronary angiography for the prediction of functional severity in true bifurcation lesions: Insights from the randomized DK-CRUSH II, III, and IV trials. AB - OBJECTIVE: This study investigated the diagnostic accuracy of three-dimensional quantitative coronary angiography (3D-QCA) compared with conventional 2D-QCA for predicting functional severity assessed by fractional flow reserve (FFR) for true bifurcation lesions. METHODS: Based on pooled data from the randomized DK-CRUSH II, III, and IV trials, we evaluated the patients with true bifurcation lesions who underwent coronary angiography together with functional evaluations using FFR in both the main vessel and the side branch. Off-line 2D- and 3D-QCA analyses were conducted using dedicated bifurcation QCA analysis software. Measurements of minimum lumen diameter (MLD), percentage diameter stenosis (% DS), and minimum lumen area (MLA) were compared between 2D- and 3D-QCA, and we evaluated their predictive values of functionally significant FFR. RESULTS: Ninety patients were eligible for enrollment in the present study. In the main vessel, MLA measured by 3D-QCA was the most accurate predictor of FFR <0.75 (C statistic 0.85, P < 0.001), while MLD measured by 2D-QCA was a similarly accurate predictor (C statistic 0.85, P < 0.001). In the side branch, the best metrics for predicting FFR <0.75 were % DS measured by 2D-QCA with a C statistic value of 0.91 (P < 0.001) and MLA measured by 3D-QCA with a C statistic value of 0.81 (P < 0.001). However, both 2D- and 3D-QCA metrics exhibited low accuracies for predicting FFR <0.75 in intermediate bifurcation lesions. CONCLUSIONS: 3D-QCA analysis for true bifurcation lesions did not improve the predictive accuracy of functionally significant FFR compared with 2D-QCA analysis. In lesions with intermediate stenosis, the diagnostic performance of both 2D- and 3D-QCA-derived measurements in differentiating functional severity is limited. PMID- 26876687 TI - Perilipin2 plays a positive role in adipocytes during lipolysis by escaping proteasomal degradation. AB - Perilipin2 (Plin2), also known as adipose differentiation-related protein (ADRP), or adipophilin, is a member of the PAT family involved in lipid droplet (LD) formation in the liver and peripheral tissues. Although Plin2 was originally identified as a highly expressed gene in adipocytes, its physiological role in mature adipocytes is largely unknown. In this report, we investigated the regulation of Plin2 expression and its function in differentiated adipocytes of mouse embryonic fibroblasts (MEFs). Plin2 mRNA levels increased during adipocyte differentiation whereas protein levels did not. Plin2 was degraded through the ubiquitin-proteasome pathway but was inhibited by lipolytic inducers. Furthermore, lentiviral-mediated Plin2 knockdown attenuated lipolysis in differentiated MEFs in a time-dependent manner. Oleic acid-induced LD formation enhanced Plin2 protein stability when it was localized to LDs. Furthermore, a mutational analysis revealed that the ubiquitination and degradation of Plin2 required both the second and third alanine in the N-terminal region. These results suggest that Plin2 is degraded in the cytosol in its N-terminal amino acid sequence-dependent manner and instead becomes stable when localized on LDs. Our findings highlight the relationship between protein stability and a previously unnoticed function of Plin2 during lipolysis in adipocytes. PMID- 26876690 TI - Effects of Brain-Computer Interface-controlled Functional Electrical Stimulation Training on Shoulder Subluxation for Patients with Stroke: A Randomized Controlled Trial. AB - The purpose of this study was to investigate the effects of brain-computer interface (BCI)-controlled functional electrical stimulation (FES) training on shoulder subluxation of patients with stroke. Twenty subjects were randomly divided into two groups: the BCI-FES group (n = 10) and the FES group (n = 10). Patients in the BCI-FES group were administered conventional therapy with the BCI FES on the shoulder subluxation area of the paretic upper extremity, five times per week during 6 weeks, while the FES group received conventional therapy with FES only. All patients were assessed for shoulder subluxation (vertical distance, VD; horizontal distance, HD), pain (visual analogue scale, VAS) and the Manual Function Test (MFT) at the time of recruitment to the study and after 6 weeks of the intervention. The BCI-FES group demonstrated significant improvements in VD, HD, VAS and MFT after the intervention period, while the FES group demonstrated significant improvements in HD, VAS and MFT. There were also significant differences in the VD and two items (shoulder flexion and abduction) of the MFT between the two groups. The results of this study suggest that BCI-FES training may be effective in improving shoulder subluxation of patients with stroke by facilitating motor recovery. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876691 TI - Insomnia symptoms, perceived stress and coping strategies in patients with systemic lupus erythematosus. AB - OBJECTIVE: The aim of this study is to evaluate perceived stress and coping strategies in individuals with systemic lupus erythematosus (SLE) according to the presence of insomnia symptoms, using a set of variables that include anxiety and depressive symptoms evaluation. METHODS: Ninety SLE women were evaluated in a cross-sectional study using the Perceived Stress Scale (PSS), Brief COPE, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Beck Depression Inventory (BDI) and Self-rating Anxiety Scale (SAS). RESULTS: Individuals with insomnia symptoms (n = 57, 66%) presented higher PSS (p < 0.001), PSQI (p < 0.0001), BDI, (p < 0.0001) scores and showed less-effective coping strategies such as the use of behavioral disengagement (p = 0.04), self blame (p = 0.02) and emotional-focused coping (p = 0.001). In a multi-regression model ISI was the independent determinant of high PSS and of behavioral disengagement; PSQI was the only determinant of self-blame (p = 0.02) and emotional-focused coping. CONCLUSIONS: SLE individuals with insomnia symptoms show high levels of perceived stress and more frequent use of disengaging and emotional-focused coping strategies. This body of evidence suggests that individuals with SLE and comorbid insomnia symptoms may therefore require additional interventions for insomnia. PMID- 26876693 TI - Indented Cu2MoS4 nanosheets with enhanced electrocatalytic and photocatalytic activities realized through edge engineering. AB - Edges often play a role as active centers for catalytic reactions in some nanomaterials. Therefore it is highly desirable to enhance catalytic activity of a material through modulating the microstructure of the edges. However, the study associated with edge engineering is less investigated and still at its preliminary stage. Here we report that Cu2MoS4 nanosheets with indented edges can be fabricated through a simple chemical etching route at room temperature, using Cu2MoS4 nanosheets with flat ones as sacrifice templates. Taking the electrocatalytic hydrogen evolution reaction (HER), photocatalytic degradation of rhodamine B (RhB) and conversion of benzyl alcohol as examples, the catalytic activity of Cu2MoS4 indented nanosheets (INSs) obtained through edge engineering was comparatively studied with those of Cu2MoS4 flat nanosheets (FNSs) without any modification. The photocatalytic tests revealed that the catalytic active sites of Cu2MoS4 nanosheets were associated with their edges rather than basal planes. Cu2MoS4 INSs were endowed with larger electrochemically active surface area (ECSA), more active edges and better hydrophilicity through the edge engineering. As a result, the as-fabricated Cu2MoS4 INSs exhibited an excellent HER activity with a small Tafel slope of 77 mV dec(-1), which is among the best records for Cu2MoS4 catalysts. The present work demonstrated the validity of adjusting catalytic activity of the material through edge engineering and provided a new strategy for designing and developing highly efficient catalysts. PMID- 26876692 TI - Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels. AB - OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE. PMID- 26876694 TI - Comparison of boron-assisted oxime and hydrazone formations leads to the discovery of a fluorogenic variant. AB - We use kinetic data, photophysical properties, and mechanistic analyses to compare recently developed high-rate constant oxime and hydrazone formations. We show that when Schiff base formation between aldehydes and arylhydrazines is carried out with an appropriately positioned boron atom, then aromatic B-N heterocycles form irreversibly. These consist of an extended aromatic structure amenable to the tailoring of specific properties such as reaction rate and fluorescence. The reactions work best in neutral aqueous buffer and can be designed to be fluorogenic - properties which are particularly interesting in bioconjugation. PMID- 26876695 TI - Jules Stein, MD: Ophthalmologist, Entertainment Magnate, and Advocate for Vision. AB - PURPOSE: To report the lifetime activities and accomplishments of Jules Stein, MD. DESIGN: Retrospective review. METHODS: Assessment of published and unpublished biographical material. RESULTS: Jules Stein combined his love of music and medicine with organizational skills to achieve successive careers as a musician, an ophthalmologist, an entertainment magnate, and an advocate for vision. To preserve vision, he founded Research to Prevent Blindness, founded the Jules Stein Eye Institute at the University of California, Los Angeles, and led a multiyear campaign to establish the National Eye Institute. CONCLUSIONS: With successive careers and extraordinary achievements, Jules Stein created an enduring legacy of benefits to ophthalmology, vision research, and the prevention of blindness. PMID- 26876697 TI - The Frequency of Signs of Meibomian Gland Dysfunction in Children with Epidermolysis Bullosa. AB - PURPOSE: To determine the frequency of meibomian gland dysfunction (MGD) in children with epidermolysis bullosa (EB). DESIGN: Hospital-based cross-sectional study. PARTICIPANTS: One hundred five children with different forms of EB. METHODS: Prospective ophthalmic examination of children with EB presenting over seventeen months including meibomian gland assessment using a recognized classification. MAIN OUTCOME MEASURES: Frequency of MGD. RESULTS: One hundred five children were recruited, 8.6% with junctional EB, 34.3% with simplex EB, 34.3% with autosomal recessive dystrophic EB, and 22.9% autosomal dominant dystrophic EB. Mean age was 7.42 years (range, 0.08-17.75 years). Ninety-two children (87.62%) demonstrated 1 or more features of MGD. CONCLUSIONS: Most children with EB exhibit signs of MGD. To the best of our knowledge, this is the first prospective ocular surface evaluation in children with EB to include lid margin evaluation using a recognized classification system. Our findings help explain some of the ocular surface anomalies seen in children with EB. PMID- 26876696 TI - Optical Coherence Tomography Angiography of Asymptomatic Neovascularization in Intermediate Age-Related Macular Degeneration. AB - PURPOSE: To determine whether angiography with swept-source (SS) optical coherence tomography (OCT) identifies subclinical type 1 neovascularization in asymptomatic eyes with intermediate age-related macular degeneration (iAMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Patients with asymptomatic iAMD in one eye and neovascular age-related macular degeneration (AMD) in their fellow eye. METHODS: The patients underwent SS OCT angiography (OCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA), and the images from these 3 angiographic techniques were compared. MAIN OUTCOME MEASURES: Identification of subclinical type 1 neovascularization with SS OCTA in asymptomatic eyes with iAMD. RESULTS: Eleven consecutive patients with iAMD in one eye and neovascular AMD in their fellow eye were imaged with FA, ICGA, and SS OCTA between August 2014 and September 2015. Clinical examination of the 11 eyes revealed drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on routine OCT imaging. Ten of the 11 eyes had no evidence of leakage on FA and 1 eye had questionable fluorescein leakage. Indocyanine green angiography revealed the presence of central macular plaques in 3 of the 11 asymptomatic eyes with iAMD, and SS OCTA revealed unambiguous type 1 neovascularization corresponding to the plaques in all 3 eyes. Optical coherence tomography angiography did not identify neovascularization in the remaining 8 eyes. CONCLUSIONS: Swept-source OCTA identified type 1 neovascularization corresponding to ICGA plaques in asymptomatic eyes with iAMD. The ability of OCTA to provide noninvasive, fast, detailed, depth-resolved identification of nonexudative neovascular lesions in eyes with iAMD suggests the need for a new classification system that distinguishes between neovascular and nonneovascular iAMD. PMID- 26876698 TI - BAP1 Germline Mutations in Finnish Patients with Uveal Melanoma. AB - PURPOSE: Germline mutations of the BRCA1-associated protein-1 gene (BAP1) predispose carriers to uveal melanoma. We report the population-based frequency of germline pathogenic variants of BAP1 in Finnish patients with uveal melanoma who live in a high-risk region for this cancer. DESIGN: Cohort study. PARTICIPANTS: In Finland, uveal melanomas are treated centrally in the Ocular Oncology Service, Helsinki University Hospital. We collected clinical data and genomic DNA from 148 of 188 consecutive patients diagnosed from January 2010 through December 2012. Seven of these patients from 6 families had a history of uveal melanoma in 1 relative, and 2 patients from 2 additional families had such a history in 2 relatives. METHODS: Sequencing BAP1. MAIN OUTCOME MEASURES: Pathogenic variants in BAP1. RESULTS: We found 2 different pathogenic variants in BAP1 in 3 patients. Two patients had a single nucleotide insertion in exon 14 resulting in a shift of reading frame. Both had a family history of uveal melanoma in at least 1 relative. One patient without a family history of uveal melanoma had a single nucleotide substitution in the conserved splice donor site of intron 2. BAP1 cancer predisposition syndrome-related cancers were present in all 3 families. The overall frequency of BAP1 pathogenic variants was 2.0% (3/148; 95% confidence interval, 0.4-5.8), the frequency among patients 50 years of age or younger was 3.6% (1/28; 95% confidence interval, 0.1-18), and a pathogenic variant was detected in 2 of 8 families with a history of uveal melanoma. CONCLUSIONS: The frequency of BAP1 germline pathogenic variants in consecutive Finnish patients with uveal melanoma who come from a high-risk region for the development of this cancer is comparable with reports from other populations. PMID- 26876699 TI - Non-hormonal interruption of incessant ovulation as a potential approach for ovarian cancer prevention. AB - Ovarian cancer is a silent killer. There is a need to intensify research efforts on prevention strategies. The causative role of incessant ovulation has been supported by the protective effect of oral hormonal contraceptives. The released follicular fluid in the process of ovulation bathes not only the surface of the ovary but also the fimbrial end of the fallopian tube. Evidence has been accumulating about a fimbrial tubal origin for ovarian high-grade serous carcinoma, and for the potential of opportunistic or elective salpingectomy as an intervention strategy. Alternatively, periodic suppression of ovulation could be beneficial among women who have no need or are not using oral hormonal contraceptives. Rupture of the ovarian follicle releasing the ovum and follicular fluid is a prostaglandin-mediated inflammatory process. It can be stopped by nonsteroidal anti-inflammatory drugs, leading to pharmacologic production of a luteinized unruptured follicle, simulating a normal non-conception cycle with unaltered steroid patterns/levels and cycle length. Non-hormonal periodic interruption of incessant ovulation could be recommended for women who are at high risk of ovarian cancer, but further research is needed to validate the potential of this approach. PMID- 26876700 TI - Evolution of surgical techniques for mandibular reconstruction using free fibula flaps: The next generation. AB - BACKGROUND: Virtual surgical planning (VSP) has contributed to a number of technical innovations in mandible reconstruction. We report on these innovations and the overall evolution of mandible reconstruction using free fibula flaps at our institution. METHODS: We performed a retrospective chart review of all patients who underwent virtually planned free fibula flap reconstruction of the mandible. Comparisons were made between cohorts based on distinct eras related to the virtual planning approach. RESULTS: Seventy-six patients underwent a total of 78 VSP-assisted mandible reconstructions with free fibula flaps. Significant differences were noted among the groups with regard to mean number of segments, percentage of flaps that had at least 3 segments, percentage of flaps that had double-barrel components, and innovations per flap. CONCLUSION: VSP-assisted mandible reconstruction has contributed to more complex surgeries at our institution. The technology ensures functional restoration, permitting an optimized aesthetic reconstruction that has not increased operative times or complications. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2066-E2073, 2016. PMID- 26876701 TI - Smouldering progress in tobacco control. PMID- 26876702 TI - Morocco's long road to comprehensive palliative care. PMID- 26876703 TI - Australia's immigration centres are no place for children. PMID- 26876704 TI - France releases interim report on drug trial disaster. PMID- 26876705 TI - NIH hopes funding increases will continue. PMID- 26876706 TI - The CONFIDeNT trial. PMID- 26876707 TI - The CONFIDeNT trial. PMID- 26876708 TI - The CONFIDeNT trial - Authors' reply. PMID- 26876709 TI - The CONFIDeNT trial. PMID- 26876710 TI - Epilepsy in women during pregnancy. PMID- 26876711 TI - Health-care improvements in a financially constrained environment. PMID- 26876712 TI - Epilepsy in women during pregnancy. PMID- 26876714 TI - A call to improve the submission process. PMID- 26876713 TI - Manochaitanya: integrating mental health into primary health care. PMID- 26876715 TI - Profiles of Childhood Trauma in Patients with Alcohol Dependence and Their Associations with Addiction-Related Problems. AB - BACKGROUND: The high occurrence of childhood trauma in individuals with alcohol dependence is well-recognized. Nevertheless, researchers have rarely studied which types of childhood trauma often co-occur and how these combinations of different types and severities of childhood trauma are related to the patients' current addiction-related problems. We aimed to identify childhood trauma profiles in patients with alcohol dependence and examined relations of these trauma profiles with the patients' current addiction-related problems. METHODS: In 347 alcohol-dependent patients, 5 types of childhood trauma (sexual abuse, physical abuse, emotional abuse, emotional neglect, and physical neglect) were measured using the Childhood Trauma Questionnaire. Childhood trauma profiles were identified using cluster analysis. The patients' current severity of addiction related problems was assessed using the European Addiction Severity Index. RESULTS: We identified 6 profiles that comprised different types and severities of childhood trauma. The patients' trauma profiles predicted the severity of addiction-related problems in the domains of psychiatric symptoms, family relationships, social relationships, and drug use. CONCLUSIONS: Childhood trauma profiles may provide more useful information about the patient's risk of current addiction-related problems than the common distinction between traumatized versus nontraumatized patients. PMID- 26876716 TI - Use of a Canine Model of Atopic Dermatitis to Investigate the Efficacy of a CCR4 Antagonist in Allergen-Induced Skin Inflammation in a Randomized Study. AB - Atopic dermatitis (AD) is an inflammatory skin disease characterized by infiltration of skin homing lymphocytes into the dermis. Most of these lymphocytes express the chemokine receptor CCR4, and the frequency of blood CCR4(+) lymphocytes correlates with AD disease severity. Canine AD is a pruritic inflammatory condition that shows many features of the human disease, including CCR4 overexpression. Therefore, we tested a potent selective CCR4 antagonist in an allergen challenge model of canine AD, both clinically and histologically, to investigate whether this chemokine pathway plays a role in the inflammatory response. Using a four-period randomized cross-over study design, 14 beagles were challenged with allergen and clinically monitored. Biopsy samples were taken before and after allergen challenge. A clear reduction of clinical scores was observed with oral prednisolone (P < 0.0001) but not for the CCR4 inhibitor. A subset of the dogs (5/13) showed partial inhibition (30-49%) of the clinical signs with CCR4 inhibitor treatment, and this finding was supported by the results of histopathologic analysis of skin biopsy samples. This partial response is consistent with redundancy in chemokine pathways and highlights the need for therapies blocking multiple pathways. This study shows the utility of this canine model of AD for testing new therapeutic agents. PMID- 26876717 TI - A Key to Genome Maze in 3D. PMID- 26876718 TI - Translational Bioinformatics: Past, Present, and Future. AB - Though a relatively young discipline, translational bioinformatics (TBI) has become a key component of biomedical research in the era of precision medicine. Development of high-throughput technologies and electronic health records has caused a paradigm shift in both healthcare and biomedical research. Novel tools and methods are required to convert increasingly voluminous datasets into information and actionable knowledge. This review provides a definition and contextualization of the term TBI, describes the discipline's brief history and past accomplishments, as well as current foci, and concludes with predictions of future directions in the field. PMID- 26876721 TI - Fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. AB - BACKGROUND: Postoperative pancreatic fistula is one of the most frequent and potentially life-threatening complications following pancreatic resections. Fibrin sealants are introduced to reduce postoperative pancreatic fistula by some surgeons. However, the use of fibrin sealants during pancreatic surgery is controversial. OBJECTIVES: To assess the safety, effectiveness, and potential adverse effects of fibrin sealants for the prevention of postoperative pancreatic fistula following pancreatic surgery. SEARCH METHODS: We searched The Cochrane Library (2015, Issue 7), MEDLINE (1946 to 26 August 2015), EMBASE (1980 to 26 August 2015), Science Citation Index Expanded (1900 to 26 August 2015), and Chinese Biomedical Literature Database (CBM) (1978 to 26 August 2015). SELECTION CRITERIA: We included all randomized controlled trials that compared fibrin sealant group (fibrin glue or fibrin sealant patch) versus control group (no fibrin sealant or placebo) in people undergoing pancreatic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes (or a Peto odds ratio for very rare outcomes), and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We included nine trials involving 1095 participants who were randomized to the fibrin sealant group (N = 550) and the control group (N = 545) after pancreatic surgery. All of the trials were at high risk of bias. There was no evidence of differences in overall postoperative pancreatic fistula (fibrin sealant 29.6%; control 31.0%; RR 0.93, 95% CI 0.71 to 1.21; P = 0.58; nine studies; low-quality evidence), postoperative mortality (3.1% versus 2.1%; Peto OR 1.29, 95% CI 0.59 to 2.82; P = 0.53; eight studies; very low-quality evidence), overall postoperative morbidity (29.6% versus 28.9%; RR 1.04, 95% CI 0.82 to 1.32; P = 0.77; five studies), reoperation rate (8.7% versus 10.7%; RR 0.80, 95% CI 0.53 to 1.21; P = 0.29; five studies), or length of hospital stay (12.9 days versus 13.1 days; MD -0.73 days, 95% CI -2.20 to 0.74; P = 0.331; six studies) between the groups. The proportion of postoperative pancreatic fistula that was clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was inadequate evidence to establish the effect of fibrin sealants on clinically significant postoperative pancreatic fistula (9.4% versus 13.4%; RR 0.72, 95% CI 0.42 to 1.21; P = 0.21; three studies). Quality of life and cost effectiveness were not reported in any of the trials. AUTHORS' CONCLUSIONS: Based on the current available evidence, fibrin sealants do not seem to prevent postoperative pancreatic fistula in people undergoing pancreatic surgery. PMID- 26876720 TI - Single-cell Transcriptome Study as Big Data. AB - The rapid growth of single-cell RNA-seq studies (scRNA-seq) demands efficient data storage, processing, and analysis. Big-data technology provides a framework that facilitates the comprehensive discovery of biological signals from inter institutional scRNA-seq datasets. The strategies to solve the stochastic and heterogeneous single-cell transcriptome signal are discussed in this article. After extensively reviewing the available big-data applications of next generation sequencing (NGS)-based studies, we propose a workflow that accounts for the unique characteristics of scRNA-seq data and primary objectives of single cell studies. PMID- 26876723 TI - The cross-mammalian neurophenomenology of primal emotional affects: From animal feelings to human therapeutics. AB - The neural correlates of human emotions are easy to harvest. In contrast, the neural constitution of emotional feelings in humans has resisted systematic scientific analysis. This review summarizes how preclinical affective neuroscience initiatives are making progress in decoding the neural nature of such feelings in animal brains. This has been achieved by studying the rewarding and punishing effects of deep brain stimulation (DBS) of subcortical emotional networks (labeled SEEING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY systems) that evoke distinct emotion action patterns, as well as rewarding and punishing effects in animals. The implications of this knowledge for development of new psychiatric interventions, especially depression, are discussed. Three new antidepressive therapeutics arising from this work are briefly noted: 1) DBS of the medial forebrain bundle (MFB) in humans, 2) reduction of psychological pain that may arise from excessive PANIC arousal, and 3) facilitation of social joy through the study of social play in rats The overall argument is that we may more readily develop new psychiatric interventions through preclinical models if we take animal emotional feelings seriously, as opposed to just behavioral changes, as targets for development of new treatments. PMID- 26876722 TI - Implementation of a telephone-based secondary preventive intervention after acute coronary syndrome (ACS): participation rate, reasons for non-participation and 1 year survival. AB - BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death from a non communicable disease. Secondary prevention is effective for reducing morbidity and mortality, but evidence-based targets are seldom reached and new interventional methods are needed. The present study is a feasibility study of a telephone-based secondary preventive programme in an unselected ACS cohort. METHODS: The NAILED (Nurse-based Age-independent Intervention to Limit Evolution of Disease) ACS trial is a prospective randomized controlled trial. All eligible patients admitted for ACS were randomized to usual follow-up by a general practitioner or telephone follow-up by study nurses. The intervention was made by continuous telephone contact, with counseling on healthy living and titration of medicines to reach target values for blood pressure and blood lipids. Exclusion criteria were limited to physical inability to follow the study design or participation in another study. RESULTS: A total of 907 patients were assessed for inclusion. Of these, 661 (72.9%) were included and randomized, 100 (11%) declined participation, and 146 (16.1%) were excluded. The main reasons for exclusion were participation in another trial, dementia, and advanced disease. "Excluded" and "declining" patients were significantly older with more co morbidity, decreased functional status, and had more seldom received education above compulsory school level than "included" patients. Non-participants had a higher 1-year mortality than participants. CONCLUSIONS: Nurse-led telephone-based follow-up after ACS can be applied to a large proportion in an unselected clinical setting. Reasons for non-participation, which were associated with increased mortality, include older age, multiple co-morbidities, decreased functional status and low level of education. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN96595458 (archived by WebCite at http://www.webcitation.org/6RlyhYTYK). Application date: 10 July 2011. PMID- 26876719 TI - Understanding Spatial Genome Organization: Methods and Insights. AB - The manner by which eukaryotic genomes are packaged into nuclei while maintaining crucial nuclear functions remains one of the fundamental mysteries in biology. Over the last ten years, we have witnessed rapid advances in both microscopic and nucleic acid-based approaches to map genome architecture, and the application of these approaches to the dissection of higher-order chromosomal structures has yielded much new information. It is becoming increasingly clear, for example, that interphase chromosomes form stable, multilevel hierarchical structures. Among them, self-associating domains like so-called topologically associating domains (TADs) appear to be building blocks for large-scale genomic organization. This review describes features of these broadly-defined hierarchical structures, insights into the mechanisms underlying their formation, our current understanding of how interactions in the nuclear space are linked to gene regulation, and important future directions for the field. PMID- 26876724 TI - Dietary-induced gestational iron deficiency inhibits postnatal tissue iron delivery and postpones the cessation of active nephrogenesis in rats. AB - Gestational iron deficiency (ID) can alter developmental programming through impaired nephron endowment, leading to adult hypertension, but nephrogenesis is unstudied. Iron status and renal development during dietary-induced gestational ID (<6 mg Fe kg-1 diet from Gestational Day 2 to Postnatal Day (PND) 7) were compared with control rats (198 mg Fe kg-1 diet). On PND2-PND10, PND15, PND30 and PND45, blood and tissue iron status were assessed. Nephrogenic zone maturation (PND2-PND10), radial glomerular counts (RGCs), glomerular size density and total planar surface area (PND15 and PND30) were also assessed. Blood pressure (BP) was measured in offspring. ID rats were smaller, exhibiting lower erythrocyte and tissue iron than control rats (PND2-PND10), but these parameters returned to control values by PND30-PND45. Relative kidney iron (ug g-1 wet weight) at PND2 PND10 was directly related to transport iron measures. In ID rats, the maturation of the active nephrogenic zone was later than control. RGCs, glomerular size, glomerular density, and glomerular planar surface area were lower than control at PND15, but returned to control by PND30. After weaning, the kidney weight/rat weight ratio (mg g-1) was heavier in ID than control rats. BP readings at PND45 were lower in ID than control rats. Altered kidney maturation and renal adaptations may contribute to glomerular size, early hyperfiltration and long term renal function. PMID- 26876728 TI - Recent Temporal Trends in Parent-Reported Physical Activity in Children in the United States, 2009 to 2014. AB - The objective of this study was to provide recent temporal trends in parent reported physical activity in children (6-11 years) between 2009 and 2014. Data from the 2009 to 2014 National Health and Nutrition Examination Survey were used. The analytic sample included 3946 children. Parent proxy of child physical activity at each of the 3 2-year cycles was assessed. For the entire sample, there was a quadratic trend, with the number of days children engaged in at least 60 min/d of physical activity increasing in the period 2011 to 2012 (6.12 days) when compared with the period 2009 to 2010 (5.96 days) and then decreasing in the period 2013 to 2014 (5.83 days). A similar quadratic trend was evident for boys, those above the poverty level, non-Hispanic whites (particularly boys), and those with less than the 85th body mass index-for-age percentile based on sex. A negative linear trend was observed for those above the poverty level and non Hispanic whites (particularly girls). In conclusion, these findings provide suggestive evidence that over the past 6 years (1999-2014), parents report that children's physical activity has slightly decreased in the latest years, with this observation being most pronounced in boys, those above the poverty level, non-Hispanic whites, and those with less than the 85th body mass index-for-age and sex percentile. Encouragingly, however, across all evaluated subpopulations, most children (55%-82%), as determined by their parents, engaged in 60 min/d of physical activity (consistent with government recommendations). PMID- 26876729 TI - Influencing referral patterns of primary care providers. PMID- 26876730 TI - Strategies for Using Plagiarism Software in the Screening of Incoming Journal Manuscripts: Recommendations Based on a Recent Literature Survey. AB - In recent years, several online tools have appeared capable of identifying potential plagiarism in science. While such tools may help to maintain or even increase the originality and ethical quality of the scientific literature, no apparent consensus exists among editors on the degree of plagiarism or self plagiarism necessary to reject or retract manuscripts. In this study, two entire volumes of published original papers and reviews from Basic & Clinical Pharmacology & Toxicology were retrospectively scanned for similarity in anonymized form using iThenticate software to explore measures to predictively identify true plagiarism and self-plagiarism and to potentially provide guidelines for future screening of incoming manuscripts. Several filters were applied, all of which appeared to lower the noise from irrelevant hits. The main conclusions were that plagiarism software offers a unique opportunity to screen for plagiarism easily but also that it has to be employed with caution as automated or uncritical use is far too unreliable to allow a fair basis for judging the degree of plagiarism in a manuscript. This remains the job of senior editors. Whereas a few cases of self-plagiarism that would not likely have been accepted with today's guidelines were indeed identified, no cases of fraud or serious plagiarism were found. Potential guidelines are discussed. PMID- 26876733 TI - Raised arterial blood pressure in neurokinin-1 receptor-deficient mice (NK1R(-/-) ): evidence for a neural rather than a vascular mechanism. AB - NEW FINDINGS: What is the central question of this study? Does genetic ablation of neurokinin-1 receptors alter arterial blood pressure? What is the main finding and its importance? NK1R(-/-) mice have increased mean arterial blood pressure, but without a concomitant change in vascular reactivity. This finding suggests that neurokinin-1 receptors play a role in the neural regulation of blood pressure. Mice with functional ablation of the neurokinin-1 receptor gene, Tacr1, (NK1R(-/-) ) express behavioural abnormalities equivalent to those seen in attention deficit hyperactivity disorder (ADHD). An established model of ADHD is the spontaneously hypertensive rat, which exhibits high blood pressure owing to increased central sympathetic drive. In light of the evidence that the neurokinin 1 receptor (NK1R) also influences cardiovascular haemodynamics, we have investigated whether NK1R(-/-) mice exhibit raised blood pressure. Cardiovascular parameters were recorded for 24 h in conscious mice using radiotelemetry. Vascular function was assessed in mesenteric resistance arteries by wire myography. The NK1R(-/-) mice exhibited a higher blood pressure than wild-type animals throughout the 24 h period. Heart rate and locomotor activity in NK1R(-/ ) mice were higher than in wild-type mice during the night period (active phase), consistent with an ADHD-like phenotype, but not during the day. Mesenteric and renal arteries from NK1R(-/-) mice exhibited normal vascular function; the responses to vasoconstrictors (U46619 and phenylephrine) and the endothelium dependent vasodilator, acetylcholine, were not altered in these animals, suggesting that the NK1R does not regulate vascular tone. Analysis of heart rate variability revealed a higher low-frequency to high-frequency ratio in NK1R(-/-) mice, indicative of increased cardiac sympathetic activity. We propose that the raised blood pressure in NK1R(-/-) mice could be due to a neural mechanism rather than a change in vascular reactivity. Further studies are required to understand this mechanism and to establish whether a subgroup of ADHD patients with polymorphism of the equivalent (TACR1) gene are affected in a similar way. PMID- 26876732 TI - Screening for Viral Pathogens in African Simian Bushmeat Seized at A French Airport. AB - Illegal bushmeat traffic is an important threat to biodiversity conservation of several endangered species and may contribute to the emergence and spread of infectious diseases in humans. The hunting, manipulation and consumption of wildlife-based products, especially those of primate origin, may be a threat to human health; however, few studies have investigated the role of bushmeat trade and consumption as a potential source of human infections to date. In this study, we report the screening of viral pathogens in African simian game seized by French customs at Toulouse Blagnac Airport. Epifluorescence microscopy revealed the presence of virus-like particles in the samples, and further metagenomic sequencing of the DNA and RNA viromes confirmed the presence of sequences related to the Siphoviridae, Myoviridae and Podoviridae bacteriophage families; some of them infecting bacterial hosts that could be potentially pathogenic for humans. To increase the sensitivity of detection, twelve pan-generic PCRs targeting several viral zoonoses were performed, but no positive signal was detected. A large-scale inventory of bacteria, viruses and parasites is urgently needed to globally assess the risk for human health of the trade, manipulation and consumption of wildlife-related bushmeat. PMID- 26876731 TI - Selective potentiation of 2-APB-induced activation of TRPV1-3 channels by acid. AB - Temperature-sensitive TRP channels are important for responses to pain and inflammation, to both of which tissue acidosis is a major contributing factor. However, except for TRPV1, acid-sensing by other ThermoTRP channels remains mysterious. We show here that unique among TRPV1-3 channels, TRPV3 is directly activated by protons from cytoplasmic side. This effect is very weak and involves key cytoplasmic residues L508, D512, S518, or A520. However, mutations of these residues did not affect a strong proton induced potentiation of TRPV3 currents elicited by the TRPV1-3 common agonist, 2-aminoethoxydiphenyl borate (2-APB), no matter if the ligand was applied from extracellular or cytoplasmic side. The acid potentiation was common among TRPV1-3 and only seen with 2-APB-related ligands. Using (1)H-nuclear magnetic resonance to examine the solution structures of 2-APB and its analogs, we observed striking structural differences of the boron containing compounds at neutral/basic as compared to acidic pH, suggesting that a pH-dependent configuration switch of 2-APB-based drugs may underlie their functionality. Supporting this notion, protons also enhanced the inhibitory action of 2-APB on TRPM8. Collectively, our findings reveal novel insights into 2 APB action on TRP channels, which should facilitate the design of new drugs for these channels. PMID- 26876734 TI - Pre-coating deproteinized bovine bone mineral (DBBM) with bone-conditioned medium (BCM) improves osteoblast migration, adhesion, and differentiation in vitro. AB - OBJECTIVES: Autogenous bone grafting has remained the gold standard for bone augmentation procedures with ability to release growth factors to the surrounding microenvironment. Recent investigations have characterized these specific growth factors released by autogenous bone chips with further isolation into a "bone conditioned medium" (BCM). The aim of the present investigation was to utilize autologous growth factors from bone chips (BCM) in combination with deproteinized bovine bone mineral (DBBM) and investigate the ability for BCM to enhance osteoblast behavior. MATERIALS AND METHODS: Mouse ST2 cells were seeded on (1) DBBM particles alone or (2) DBBM + BCM. Thereafter, samples were compared for cell recruitment, adhesion, proliferation, and real-time PCR for osteoblast differentiation markers including Runx2, collagen 1 alpha 2 (COL1A2), alkaline phosphatase (ALP), and osteocalcin (OCN). Alizarin red staining was used to assess mineralization. RESULTS: Coating BCM on DBBM particles improved cell migration of ST2 cells and significantly enhanced a 2-fold increase in cell adhesion. While no significant increase in cell proliferation was observed, BCM significantly increased mRNA levels of COL1A2, ALP, and OCN at 3 days post seeding. Furthermore, a 3-fold increase in alizarin red staining was observed on DBBM particles pre-coated with BCM. CONCLUSION: Pre-coating DBBM with BCM enhanced the osteoconductive properties of DBBM by mediating osteoblast recruitment, attachment, and differentiation towards bone-forming osteoblasts. Future animal study is necessary to further characterize the added benefit of BCM as an autogenous growth factor source for combination therapies. CLINICAL RELEVANCE: The application of BCM in combination with biomaterials may serve as an autogenous growth factor source for bone regeneration. PMID- 26876735 TI - Shaping ability of two nickel-titanium instruments activated by continuous rotation or adaptive motion: a micro-computed tomography study. AB - OBJECTIVES: The objective of the study was to evaluate the shaping ability of curved root canals using Twisted File Adaptive (TFA) files (SybronEndo, Orange, CA) and Mtwo (Sweden & Martina, Padova, Italy) activated by continuous rotation or adaptive motion. MATERIALS AND METHODS: Thirty-two mandibular molars with two separate mesial canals and severe angles of curvature were selected. Each canal was randomly assigned to one of the four experimental groups (n = 16): TFA and Mtwo files used in continuous rotation (groups 1 and 3) or in adaptive motion (groups 2 and 4). Root canals before and after preparation were assessed by micro computed tomography. Volume, surface area, canal transportation, and centering ability were recorded and analyzed using two-way analyses of variance. RESULTS: Volume and surface area increased less with TFA files in continuous rotation than in other groups (P < 0.001 and P < 0.01, respectively, for each comparison) that were not different (P > 0.05). TFA files had significantly less transportation and higher centering ability than Mtwo both in continuous and adaptive motion (P < 0.0001). Centering ratio, but not canal transportation, was improved by adaptive motion compared with continuous rotation for both instruments (P < 0.01). However, no differences were found in canal transportation and centering ability in the apical third for both instruments and motions (P > 0.05). CONCLUSIONS: No difference between the devices and kinematics was found in the apical third; TFA performed significantly better in the middle and coronal parts of the root canal. CLINICAL RELEVANCE: The use of NiTi files made by heat-treated alloy and/or adaptive motion could improve the qualities of root canal shaping rather than the use of conventional NiTi instruments and/or continuous rotation in the coronal and middle thirds of the root canals, but not in the apical one. Moreover, these findings encourage the use of adaptive motion with conventional NiTi files to improve centering ability without affecting other preparation qualities of root canals. PMID- 26876737 TI - Change in risk factors for eating disorder symptomatology in Malay students sojourning in the United Kingdom. AB - OBJECTIVE: The purpose of this investigation was to examine change in risk for eating disorders in higher education students sojourning in the United Kingdom (UK), as well as associations between such risk and experiences in the host culture. METHOD: Participants were 98 female students from Malaysia, who completed a measure of risk factors for eating disorder symptomatology (the Eating Disorder Inventory-3 subscales of drive for thinness, body dissatisfaction, and bulimia symptoms) at two time points: two months prior to beginning their sojourn in the UK (Time 1) and four months after the sojourn began (Time 2). At Time 2, participants also completed measures of sociocultural adjustment, cultural distance between home and host cultures, and perceived discrimination in the host culture. RESULTS: Analyses indicated that, compared to scores at Time 1, participants had significantly higher drive for thinness (d = 0.64), body dissatisfaction (d = 0.54), and bulimia symptoms (d = 0.29) at Time 2. Poorer sociocultural adjustment and greater perceived discrimination significantly predicted greater risk of eating disorders at Time 2. DISCUSSION: The stress associated with culture change may place sojourning students at risk for disordered eating. Further research is needed to determine the extent to which this risk is related to culture-change specifically, as opposed to a general set of factors associated with transition-related psychopathology more broadly. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:695-700). PMID- 26876738 TI - Colloidal Synthesis of Lettuce-like Copper Sulfide for Light-Gating Heterogeneous Nanochannels. AB - Lettuce-like CuxS micron particles were successfully prepared by a colloidal hot injection method, and the preliminary evaluation of the light-gating artificial ionic nanochannels designed using these particles was also demonstrated. A likely underlying mechanism behind the formation of the lettuce architecture was tentatively proposed via monitoring the evolution process. These particles are hydrophobic and possess a high surface area that can readily absorb the light responsive 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran (Spiro) molecules. Finally, the heterogeneous nanochannels were constructed by spin-coating the preprepared CuxS particles loaded with Spiro onto the commercially available anodic alumina (AAO) substrate. The AAO-CuxS/Spiro heterogeneous nanochannels "close" under illumination of ultraviolet light (365 nm) and then "open" by visible light irradiation, which exhibits a regulated ionic transport property with good responsive switchability and stability. PMID- 26876736 TI - Effects of topical corticosteroid administration on intraocular pressure in normal and glaucomatous cats. AB - OBJECTIVE: The objective of this study was to determine the effect of topical corticosteroid (CCS) therapy on intraocular pressure (IOP) in normal cats and cats with primary feline congenital glaucoma (FCG). ANIMALS STUDIED: Five normal and 11 FCG cats were studied in two cohorts. PROCEDURES: IOP was measured by a single, masked observer, once daily, 3-5 days/week throughout the course of CCS treatment and for up to 11 days after treatment discontinuation. One eye per cat was randomly assigned for treatment twice daily with CCS; balanced salt solution (BSS) applied to the contralateral eye served as a control. Differences between eyes and between weeks of the study period were calculated for each cat. A positive response to CCS was defined as a consistent >15% or >25% higher IOP in the treated relative to control eye in normal and FCG cats, respectively. RESULTS: A total of 8 of 11 FCG cats responded to topical CCS after 1-5 weeks of treatment with an increase in IOP relative to the untreated eye (maximum IOP discrepancy of 56 mmHg). Two of five normal cats responded to topical CCS with an appreciable, but clinically unimportant increase in IOP in the treated eye (maximum IOP discrepancy of 6.4 mmHg). CONCLUSIONS: Our data indicate that the incidence of steroid-induced IOP elevation in cats is lower than that of previously published feline studies. Cats with preexisting compromise in aqueous humor outflow may show a greater, clinically relevant response to topical CCS than normal cats. PMID- 26876739 TI - Effects of nicotinic receptor agonists on bladder afferent nerve activity in an in vitro bladder-pelvic nerve preparation. AB - Effects of nicotinic receptor agonists (epibatidine and nicotine) on mechano sensitive bladder afferent nerve (MS-BAN) activity were studied in an in vitro bladder-pelvic afferent nerve preparation. MS-BAN activity was induced by isotonic distention of the bladder at pressures of 10-40 cmH2O. The effect of epibatidine varied according to the concentration, route of administration and the intravesical pressure stimulus. Epibatidine (300-500 nM) administered in the perfusate to the serosal surface of the bladder decreased distension evoked afferent firing by 30-50% depending on the bladder pressure. However these concentrations also produced an immediate increase in tonic afferent firing in the empty bladder. Lower concentrations (50-100 nM) elicited weaker and more variable effects. The inhibitory effects were blocked by bath application of mecamylamine (150 uM) a nicotinic receptor antagonist. Bath application of nicotine (20 uM) elicited similar effects. Intravesical administration of epibatidine (500 nM) significantly increased MS-BAN firing by 15-30%; while lower concentrations (200-300 nM) were ineffective. This facilitatory effect of epibatidine was blocked by intravesical administration of mecamylamine (250 uM). Electrical stimulation on the surface of the bladder elicited action potentials (AP) in BAN. Bath application of epibatidine (300 nM) or nicotine (20 uM) did not change either the voltage threshold or the area of evoked AP. These results indicate that nicotinic agonists: (1) enhance MS-BAN activity originating at afferent receptors near the urothelium, (2) inhibit MS-BAN activity originating at afferent receptors located at other sites in the bladder, (3) directly excite unidentified afferents, (4) do not alter afferent axonal excitability. PMID- 26876740 TI - Learning impairment by minimal cortical injury in a mouse model of Alzheimer's disease. AB - Brain injury accelerates amyloid-beta (Abeta) deposits and exacerbates Alzheimer's disease (AD). Accumulation of intracellular soluble Abeta impairs cognition prior to emergence of Abeta plaques. However, it is not known whether brain injury affects learning impairment attributable to intracellular soluble Abeta. We made a small injury by injecting glutamate into the parietal cortex in 3xTg AD mice of 4-5 months old, at which age soluble Abeta is accumulated without Abeta deposits. The size of glutamate-induced lesion was significantly larger than that of saline-injected control lesion. We reduced the relative difficulty of Morris water maze (MWM) task by repeating it twice, so that saline-injected 3xTg mice could perform as well as wild-type control mice. Under this condition, glutamate-injected 3xTg mice exhibited learning deficits. DNA microarray analysis revealed that 3 genes are upregulated, with one gene downregulated, more than 2 folds in the hippocampus. These 4 genes do not appear to be involved directly in learning but may be a part of signal cascade triggered by glutamate-induced small injury. Hippocampal content of soluble Abeta1-42 was increased in the glutamate 3xTg group. Facilitation of large-conductance calcium-activated potassium (BK) channel accompanied learning recovery in the saline-control 3xTg group in agreement with our previous reports, in which learning deficits attributable to intracellular Abeta were alleviated by facilitating BK channels. However, BK channel remained suppressed in the glutamate 3xTg group. It is suggested that glutamate-induced injury worsens learning by enhancing the toxicity of soluble Abeta or increasing its content per se. PMID- 26876741 TI - Altered hypothalamic inflammatory gene expression correlates with heat stroke severity in a conscious rodent model. AB - It has been suggested that heat-induced hypothalamic damage mediates core temperature (Tc) disturbances during heat stroke (HS) recovery; this is significant as hypothermia and/or fever have been linked to severity and overall pathological insult. However, to date there has been a lack of histological evidence in support of these claims. We hypothesized that local hypothalamic cytokines and/or chemokines, known regulators of Tc, are mediating the elevation in Tc during HS recovery even in the absence of histological damage. In experiment 1, the hypothalamus of Fischer 344 rats was examined for 84 cytokine/chemokine genes (real-time PCR) at multiple time points (Tc,Max, 1, 3, and 10 days) during mild HS recovery. In experiment 2, the hypothalamus of three different HS severities (MILD, moderate [MOD], and severe [SEV]) in rats were examined for the same genes as experiment 1 as well as six oxidative damage markers, at a single intermediate time point (1 day). Systemic cytokines were also analyzed in experiment 2 across the three severities. There were significant alterations in 25 cytokines/chemokines expression at Tc,Max, but little or no changes in expression at longer time points in experiment 1. In experiment 2 there were significant changes in gene expression in SEV rats only, with MILD and MOD rats showing baseline expression at 1 day, despite an absence of systemic cytokine expression in any severity. There was also no change in any oxidative marker of damage at 1 day, regardless of severity. In conclusion, we show only limited changes during long term recovery from HS, but demonstrate differences in hypothalamic gene expression patterns that may be driving HS pathology and morbidity. These findings contribute to our overall understanding of HS pathology in the CNS, as well as providing avenues for future pharmacological intervention. PMID- 26876742 TI - Development and validation of a reliable and rapid LC-MS/MS method for simultaneous quantification of sacubitril and valsartan in rat plasma and its application to a pharmacokinetic study. AB - A selective, sensitive and rapid liquid chromatographic method with electrospray ionization tandem mass spectrometric detection has been developed and validated for simultaneous quantification of sacubitril and valsartan in rat plasma using telmisartan as internal standard (IS). The analytes were extracted by deprotenization of 50 MUL of plasma sample using 200 MUL of acetonitrile. In a short chromatographic run of 1.50 min run time, separation was achieved on a Hypersil Gold C18 column using a mobile phase composed of 0.1% formic acid in Milli-Q water-0.1% formic acid in acetonitrile in gradient elution mode. The quantification of target compounds was performed in a positive electrospray ionization mode and multiple reaction monitoring. Response was a linear function of concentration in the ranges of 0.5-20,000 ng/mL for both analytes, with r(2) > 0.9997. The intra- and inter-day precision and accuracy results were <15% and acceptable as per US Food and Drug Administration guidelines. Stability of compounds were established in a battery of stability studies, i.e. bench-top, autosampler and long-term storage stability as well as freeze-thaw cycles. The validated method can be used as a routine method to support pharmacokinetic studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876743 TI - Virtual planning and guided surgery in fibular free-flap mandibular reconstruction: A 29-case series. AB - INTRODUCTION: Virtual planning and guided surgery (VPGS) has been recently developed for mandibular reconstruction, but benefit remains to be assessed. The aim of this study was to analyze the impact of VPGS on operative time and postoperative course. MATERIAL AND METHODS: All patients who underwent fibula free-flap mandibular reconstruction between 2013 and 2014 in our institution were included in a retrospective study. Operative times and postoperative course were compared between patients who underwent conventional surgery in 2013 and those who underwent VPGS in 2014. RESULTS: A total of 29 patients were included: 11 in 2013 and 18 in 2014. Taking all types of mandibular defect together, ischemia time was significantly decreased by VPGS (75min, vs 150min for conventional surgery; P<0.001), whereas overall operative time was not significantly reduced (481 and 516min, respectively; P=0.4). VPGS had no impact on postoperative course: local or general complications, time to decannulation and nasogastric tube removal, or length of stay. CONCLUSION: VPGS significantly reduced fibula free-flap ischemia time. Long-term functional and esthetic benefit remains to be evaluated. PMID- 26876744 TI - Early impact of rotavirus vaccination in a large paediatric hospital in the UK. AB - The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0-15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-series analysis demonstrated that, post vaccine introduction (July 2013 to June 2015), CA- and HA-RVGE hospitalizations were 83% [95% confidence interval (CI): 72-90%) and 83% (95% CI: 66-92%] lower than expected, respectively. Rotavirus vaccination has rapidly reduced the hospital rotavirus disease burden among both CA- and HA-RVGE cases. PMID- 26876745 TI - Fatal acquisition of vanD gene during vancomycin treatment of septicaemia caused by Enterococcus faecium. PMID- 26876746 TI - Trends in the distribution and antimicrobial susceptibility of causative pathogens of device-associated infection in Korean intensive care units from 2006 to 2013: results from the Korean Nosocomial Infections Surveillance System (KONIS). AB - BACKGROUND: For all countries, information on pathogens causing healthcare associated infections is important in order to develop proper strategies for preventing and treating nosocomial infections. AIM: To assess the change in frequencies and antimicrobial resistance of pathogens causing device-associated infections (DAIs) in intensive care units (ICUs) in South Korea between July 2006 and June 2014. METHODS: Data from the Korean Nosocomial Infections Surveillance System (KONIS) were analysed, including three major DAI types in ICUs. FINDINGS: The frequency of Gram-negative bacteria gradually increased for central line associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) (from 24.6% to 32.6% and from 52.8% to 73.5%, respectively). By contrast, the frequency of Gram-positive bacteria decreased from 58.6% to 49.2% for CLABSI, and from 44.3% to 23.8% for VAP (P < 0.001). Staphylococcus aureus was the most frequent causative pathogen in CLABSI throughout the surveillance period, but for VAP was replaced as the most frequent pathogen by Acinetobacter baumannii as of 2010. Candida albicans was the most frequent pathogen for catheter-associated urinary tract infection. The meticillin resistance rate in S. aureus decreased from 95% to 90.2% (P < 0.001); amikacin resistance in Klebsiella pneumoniae and Escherichia coli decreased from 43.8% to 14.7% and from 15.0% to 1.8%, respectively (P < 0.001); imipenem resistance in A. baumannii increased from 52.9% to 89.8% (P < 0.001). CONCLUSION: The proportion of Gram-negative bacteria as nosocomial pathogens for CLABSI and VAP has increased. The prevalence of A. baumannii causing DAIs in Korean ICUs has increased rapidly, as has the rate of carbapenem resistance in these bacteria. PMID- 26876747 TI - Pseudo-outbreaks of Stenotrophomonas maltophilia on an intensive care unit in England. AB - BACKGROUND: In June 2014, a cluster of identical S. maltophilia isolates was reported in an adult intensive care unit (ICU) at a district general hospital. An outbreak control team was convened to investigate the cluster and inform control measures. AIM: To identify potential risk factors for isolation of S. maltophilia in this setting. METHODS: We conducted a cohort study of ICU patients for whom a bronchoalveolar lavage (BAL) specimen was submitted between October 2013 and October 2014. Cases were patients with S. maltophilia-positive BAL. We calculated the association between isolation of S. maltophilia and patient characteristics using risk ratios (RRs) with 95% confidence intervals (95% CIs) and univariate logistic regression. Chi-squared or Fisher's exact tests were used. BAL specimens were microbiologically typed using pulse-field gel electrophoresis (PFGE). FINDINGS: Eighteen patients met the case definition. Two patients had clinical presentations that warranted antibiotic treatment for S. maltophilia. All cases were exposed to bronchoscopy. PFGE typing revealed clusters of two strain types. We found statistically significant elevated risks of isolating BRISPOSM-4 in patients exposed to bronchoscope A (RR: 13.56; 95% CI: 1.82-100; P < 0.001) and BRISPOSM-3 in patients exposed to bronchoscope B (RR: 16.89; 95% CI: 2.14-133; P < 0.001). S. maltophilia type BRISPOSM-4 was isolated in water used to flush bronchoscope A after decontamination. CONCLUSION: Two pseudo-outbreaks occurred in which BAL specimens had been contaminated by reusable bronchoscopes. We cannot exclude the potential for colonization of the lower respiratory tract of exposed patients. Introduction of single-use bronchoscopes was an effective control measure. PMID- 26876748 TI - Significant intolerability of efavirenz in HIV occupational postexposure prophylaxis. AB - BACKGROUND: Completion of human immunodeficiency virus (HIV) occupational postexposure prophylaxis (PEP) is important for successful prophylaxis. AIM: To determine factors associated with failure to complete the four-week HIV PEP. METHODS: A retrospective study was conducted among healthcare workers (HCWs) accidentally exposed to blood or body fluids of patients at the Bamrasnaradura Infectious Diseases Institute, Thailand, between March 1996 and June 2014. Logistic regression analysis was used to determine factors associated with failure to complete the four-week HIV PEP. FINDINGS: In total, 225 exposure episodes were reported. The mean age of HCWs was 33.1 (standard deviation 9.9) years, and 189 (84%) were female. Nurses (43%) were exposed most frequently. The HIV status of the source was defined in 149 (66%) episodes, and 101 (68%) of these were positive. Of 225 exposures, PEP was prescribed in 155 (69%) cases, with intentional discontinuation in 26 cases. Ninety-one of 129 (71%) HCWs completed the four-week regimen. Multi-variate analysis showed that a regimen of two nucleotide reverse transcriptase inhibitors (NRTI) + efavirenz (EFV) was the only significant factor associated with non-completion of the four-week course (odds ratio 37.8, 95% confidence interval 4.2-342.3; P < 0.01). Other factors including age, sex, staff position, status of the source and other PEP regimens were not associated with non-completion of the four-week course (P > 0.05). None of the HCWs were documented to have HIV seroconversion. CONCLUSION: A regimen of two NRTIs + EFV was significantly associated with premature discontinuation of occupational PEP. This regimen should not be used for HIV prophylaxis following occupational exposure. PMID- 26876749 TI - Management of a hospital outbreak of extensively drug-resistant Acinetobacter baumannii using a multimodal intervention including daily chlorhexidine baths. AB - BACKGROUND: Extensively drug-resistant Acinetobacter baumannii (XDR-Ab) is an increasingly important cause of healthcare-associated infection. Uncertainties remain concerning optimal control measures for healthcare-associated outbreaks. AIM: To describe the epidemiology and control of an XDR-Ab outbreak that involved multiple units of a large hospital from March 2012 to January 2014. METHODS: Case finding included screening of rectum, groin, throat, nose, wounds, iatrogenic portals of entry, and catheterized sites. Antimicrobial susceptibility was evaluated by disc diffusion and E-test. Resistance genes were detected by polymerase chain reaction. Clonality was assessed by pulsed-field gel electrophoresis. Charts of cases were reviewed to identify risk factors for invasive infection. Control measures included isolation and cohorting of cases, hand hygiene reinforcement, environmental decontamination, and source control with daily baths using wipes pre-impregnated with chlorhexidine gluconate. FINDINGS: A single clonal strain of XDR-Ab colonized or infected 29 patients. Five patients died of XDR-Ab bacteraemia. Transmission occurred primarily on two wards. Colonization was detected at all anatomical screening sites; only 57% (16/28) of cases were rectal carriers. Advanced malignancy was a risk factor for bacteraemia (relative risk: 5.8; 95% confidence interval: 1.2-27.0). Transmission ended following implementation of the multimodal control strategy. No additional nosocomial cases occurred during the following 20 months. CONCLUSION: Our study highlights the need to screen multiple anatomic sites to diagnose carriage and identifies risk factors for XDR-Ab bacteraemia. A multimodal intervention that included daily chlorhexidine baths for cases was rapidly followed by the termination of the outbreak. Hospitals should consider similar interventions when managing future XDR-Ab outbreaks. PMID- 26876751 TI - Magnesium and manganese binding sites on proteins have the same predominant motif of secondary structure. AB - Manganese ion (Mn(2+)) can substitute magnesium ion (Mg(2+)) in active sites of numerous enzymes. Binding sites for these two ions have been studied in two sets of protein 3D structures from the Protein Data Bank with the homology level lower than 25%. The structural motif "beta strand - binder - random coil" is predominant in both Mn(2+) and Mg(2+) coordination spheres, especially in functionally relevant ones. That predominant motif works as an active binder of those divalent cations which can then attract additional ligands, such as different phosphate-containing compounds. In contrast, such Mg(2+) and Mn(2+) binding motif as "GK(T/S)T" being the N-terminal part of alpha helices works as an active binder of phosphates which can then attract divalent cations. There are few differences between Mg(2+) and Mn(2+) coordination spheres responsible of the cation specificity. His residues are underrepresented in certain positions around Asp and Glu residues involved in Mg(2+) coordination, while they are overrepresented in certain positions around Asp and Glu residues coordinating Mn(2+). The random coil region in the "beta strand - random coil - alpha helix" motif for Mg(2+) binding is usually shorter than that in the same motif for Mn(2+) coordination. This feature is associated with the lower number of binding amino acids (and lower levels of usage of such "major" binders as Asp and Glu) for Mg(2+) (which is a hard Lewis acid) in comparison with those for Mn(2+) (an intermediate Lewis acid). PMID- 26876750 TI - Periodic patterning of the Drosophila eye is stabilized by the diffusible activator Scabrous. AB - Generation of periodic patterns is fundamental to the differentiation of multiple tissues during development. How such patterns form robustly is still unclear. The Drosophila eye comprises ~750 units, whose crystalline order is set during differentiation of the eye imaginal disc: an activation wave sweeping across the disc is coupled to lateral inhibition, sequentially selecting pro-neural cells. Using mathematical modelling, here we show that this template-based lateral inhibition is highly sensitive to spatial variations in biochemical parameters and cell sizes. We reveal the basis of this sensitivity, and suggest that it can be overcome by assuming a short-range diffusible activator. Clonal experiments identify Scabrous, a previously implicated inhibitor, as the predicted activator. Our results reveal the mechanism by which periodic patterning in the fly eye is stabilized against spatial variations, highlighting how the need to maintain robustness shapes the design of patterning circuits. PMID- 26876752 TI - Maximal gene number maintainable by stochastic correction - The second error threshold. AB - There is still no general solution to Eigen's Paradox, the chicken-or-egg problem of the origin of life: neither accurate copying, nor long genomes could have evolved without one another being established beforehand. But an array of small, individually replicating genes might offer a workaround, provided that multilevel selection assists the survival of the ensemble. There are two key difficulties that such a system has to overcome: the non-synchronous replication of genes, and their random assortment into daughter cells (the units of higher-level selection) upon fission. Here we find, using the Stochastic Corrector Model framework, that a large number (tau>=90) of genes can coexist. Furthermore, the system can tolerate about 10% replication rate asymmetry (competition) among the genes. On this basis, we put forward a plausible (and testable!) scenario for how novel genes could have been incorporated into early living systems: a route to complex metabolism. PMID- 26876753 TI - Efficacy of Schwann cell transplantation for spinal cord repair is improved with combinatorial strategies. AB - When cells (including Schwann cells; SCs) of the peripheral nervous system (PNS) could be purified and expanded in number in tissue culture, Richard Bunge in 1975 envisioned that the SCs could be introduced to repair the central nervous system (CNS), as SCs enable axons to regenerate after PNS injury. Importantly, autologous human SCs could be transplanted into injured human spinal cord. Availability of the new culture systems to study interactions between sensory neurons, SCs and fibroblasts increased our knowledge of SC biology in the 1970s and '80s. Joining the Miami Project to Cure Paralysis in 1989 brought the opportunity to use this knowledge to initiate spinal cord repair studies. Development of a rat complete spinal cord transection/SC bridge model allowed the demonstration that axons regenerate into the SC bridge. Together with study of contused rat spinal cord, it was concluded that implanted SCs reduce cavitation, protect tissue around the lesion, support axon regeneration and form myelin. SC transplantation efficacy was improved when combined with neurotrophins, elevation of cyclic AMP levels, olfactory ensheathing cells, a steroid or chondroitinase. Increased efficacy meant higher numbers of axons, particularly from the brainstem, and more SC-myelinated axons in the implants and improvement in hindlimb movements. Human SCs support axon regeneration as do rat SCs. Astrocytes at the SC bridge-host spinal cord interfaces play a key role in determining whether axons enter the SC milieu. The SC work described here contributed to gaining approval from the FDA for an initial autologous human SC clinical trial (at the Miami Project) that has been completed and found to be safe. PMID- 26876754 TI - Peripheral neurosteroids enhance P2X receptor-induced mechanical allodynia via a sigma-1 receptor-mediated mechanism. AB - The role of peripheral neurosteroids and their related mechanisms on nociception have not been thoroughly investigated. Based on emerging evidence in the literature indicating that neurosteroids and their main target receptors, i.e., sigma-1, GABAA and NMDA, affect P2X-induced changes in neuronal activity, this study was designed to investigate the effect of peripherally injected dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulfate (PREGS) on P2X receptor-mediated mechanical allodynia in rats. Intraplantar injection of either neurosteroids alone did not produced any detectable changes in paw withdrawal frequency to the innocuous mechanical stimulation in naive rats. However, When DHEAS or PREGS were co-injected with a sub-effective dose of alphabetameATP, mechanical allodynia was developed and this was dose dependently blocked by pre injection of the P2X antagonist, TNP-ATP. These results demonstrates that DHEAS and PREGS potentiate the activity of P2X receptors which results in the enhancement of alphabetameATP-induced mechanical allodynia. In order to investigate the potential role of peripheral sigma-1, GABAA and NMDA receptors in this facilitatory action, we pretreated animals with BD-1047 (a sigma-1 antagonist), muscimol (a GABAA agonist) or MK-801 (a NMDA antagonist) prior to DHEAS or PREGS+alphabetameATP injection. Only BD-1047 effectively prevented the facilitatory effects induced by neurosteroids on alphabetameATP-induced mechanical allodynia. Collectively, we have shown that peripheral neurosteroids potentiate P2X-induced mechanical allodynia and that this action is mediated by sigma-1, but not by GABAA nor NMDA, receptors. PMID- 26876755 TI - Metformin prevents cerebellar granule neurons against glutamate-induced neurotoxicity. AB - Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders. PMID- 26876756 TI - Ecological momentary assessment of affect and craving in patients in treatment for prescription opioid dependence. AB - Low positive affect (PA) is likely to contribute to risk of relapse; however, it has received relatively little attention in clinical research. This study examined the associations among positive affect, negative affect (NA), and craving in medically withdrawn patients using ecological momentary assessment (EMA). Participants (n=73) provided reports of their PA, NA, and craving 4 times a day for an average of 10.47 (SD=3.80) days. Person- and day-level associations between PA, NA, and craving were examined using multilevel models. A significant interaction emerged between person- and day-level PA such that PA on the day level was negatively associated with craving for individuals experiencing low mean PA throughout the study. No significant interaction emerged between person- and day-level NA. The main effects for both person- and day-level NA were significant. Individuals experiencing high NA throughout the study experienced higher craving overall and on days when NA was higher than usual, craving was also higher. Results suggest that high person- and day-level NA may directly contribute to the risk for relapse via increased craving, whereas low day- level PA may contribute to risk for relapse among individuals exhibiting low person level PA via increased craving on days with lower than average levels of PA for those individuals. Given that there is a paucity of research relating low PA to craving, continued investigation into how and when low PA creates risk for relapse is warranted. PMID- 26876757 TI - Brain-derived neurotrophic factor promotes vesicular glutamate transporter 3 expression and neurite outgrowth of dorsal root ganglion neurons through the activation of the transcription factors Etv4 and Etv5. AB - Brain-derived neurotrophic factor (BDNF) is critical for sensory neuron survival and is necessary for vesicular glutamate transporter 3 (VGLUT3) expression. Whether the transcription factors Etv4 and Etv5 are involved in these BDNF induced effects remains unclear. In the present study, primary cultured dorsal root ganglion (DRG) neurons were used to test the link between BDNF and transcription factors Etv4 and Etv5 on VGLUT3 expression and neurite outgrowth. BDNF promoted the mRNA and protein expression of Etv4 and Etv5 in DRG neurons. These effects were blocked by extracellular signal-regulated protein kinase 1/2 (ERK1/2) inhibitor PD98059 but not phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or phospholipase C-gamma (PLC-gamma) inhibitor U73122. Etv4 siRNA and Etv5 siRNA effectively blocked the VGLUT3 expression and neurite elongation induced by BNDF. The overexpression of Etv4 or Etv5 potentiated the effects of BNDF-induced neurite elongation and growth-associated protein 43 (GAP-43), medium neurofilament (NF-M), and light neurofilament (NF-L) expression while these effects could be inhibited by Etv4 and Etv5 siRNA. These data imply that Etv4 and Etv5 are essential transcription factors in modulating BDNF/TrkB signaling mediated VGLUT3 expression and neurite outgrowth. BDNF, through the ERK1/2 signaling pathway, activates Etv4 and Etv5 to initiate GAP-43 expression, promote neurofilament (NF) protein expression, induce neurite outgrowth, and mediate VGLUT3 expression for neuronal function improvement. The biological effects initiated by BDNF/TrkB signaling linked to E26 transformation-specific (ETS) transcription factors are important to elucidate neuronal differentiation, axonal regeneration, and repair in various pathological states. PMID- 26876758 TI - Resveratrol provides neuroprotection by inhibiting phosphodiesterases and regulating the cAMP/AMPK/SIRT1 pathway after stroke in rats. AB - Dysfunction of energy metabolism can be a significant and fundamental pathophysiological basis for strokes. In studies of both humans and rodents, resveratrol, a natural polyphenol, has been reported to provide protection from cerebral ischemic injury by regulating expression of silent mating type information regulation 2 homolog 1 (SIRT1). However, direct evidence demonstrating that resveratrol exerts neuroprotection from cerebral ischemia injury by decreasing energy consumption is still lacking. Therefore, the aim of this study was to elucidate the mechanisms and signaling pathways through which resveratrol regulates energy metabolism in the ischemic brain, and to identify potential targets of resveratrol. ATP levels in brain tissues were detected by high performance liquid chromatography. SIRT1 and the phosphorylation of adenosine-monophosphate-activated protein kinase (P-AMPK) expressiones were evaluated by western blot. Levels of phosphodiesterase (PDEs) and cAMP were quantitated by real-time PCR and ELISA, respectively. Results showed that resveratrol significantly reduced the harmful effects of cerebral ischemic injury in vivo. Moreover, levels of ATP, p-AMPK, SIRT1, and cAMP were increased by resveratrol and PDE inhibitors. In conclusion, our findings indicate that resveratrol provides neuroprotection by inhibiting PDEs and regulating the cAMP/AMPK/SIRT1 pathway, which reduces ATP energy consumption during ischemia. PMID- 26876759 TI - Contrasting regional Fos expression in adolescent and young adult rats following acute administration of the antidepressant paroxetine. AB - Adolescents and adults may respond differently to antidepressants, with poorer efficacy and greater probability of adverse effects in adolescents. The mechanisms underlying this differential response are largely unknown, but likely relate to an interaction between the neural effects of antidepressants and brain development. We used Fos immunohistochemistry to examine regional differences in adolescent (postnatal day (PND) 28) and young adult (PND 56) male, Wistar rats given a single injection of the selective serotonin reuptake inhibitor paroxetine (10mg/kg). Paroxetine induced widespread Fos expression in both adolescent and young adult rats. Commonly affected areas include the bed nucleus of the stria terminalis (dorsolateral), medial preoptic area, paraventricular hypothalamic and thalamic nuclei and central nucleus of the amygdala. Fos expression was generally lower in adolescents with significantly greater Fos expression observed in young adults in the prelimbic cortex, supraoptic nucleus, basolateral amygdala, lateral parabrachial and Kolliker-Fuse nuclei. However, a small subset of regions showed greater adolescent Fos expression including the nucleus accumbens shell, lateral habenula and dorsal raphe. Paroxetine increased plasma corticosterone concentrations in young adults, but not adolescents. Plasma paroxetine levels were not significantly different between the age groups. These results indicate a different c-Fos signature of acute paroxetine in adolescent rats, with greater activation in key mesolimbic and serotonergic regions, but a more subdued cortical, brainstem and hypothalamic response. This suggests that the atypical response of adolescents to paroxetine may be related to a blunted neuroendocrine response, combined with insufficient top-down regulation of limbic regions involved in reward and impulsivity. PMID- 26876760 TI - Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles. AB - Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer. PMID- 26876761 TI - Energy restriction impairs dendritic cell development in C57BL/6J mice. AB - Dendritic cells (DC) are antigen-presenting cells known for stimulating naive T lymphocytes. The sequential stages of DC development from common myeloid progenitors have been elucidated in murine bone marrow. Energy-restriction (ER) is a pro-longevity dietary intervention with mixed immunological outcomes. The objective of this study was to examine the development of DC in adult C57Bl6J mice fed a 40% ER diet. We observed increased myeloid progenitors, but decreased common DC progenitors, precursor conventional DC and plasmacytoid DC. Furthermore, we observed increased macrophages and cells expressing CD169 in the bone marrow of ER mice. There was no significant difference in DC subsets from unfractionated ER and ad libitum-fed murine bone marrow samples cultured in GM CSF-supplemented media or Flt3L-supplemented media. Examining rates of proliferation with 6h BrdU incorporation and Ki-67 staining showed these DC progenitor populations have different proliferation rates in ER compared with AL mice. We show here, for the first time, ER results in altered myelopoiesis resulting in reduced DC development but enhanced monocyte/macrophage development in steady-state C57Bl6J mice. In conclusion, these data may partially explain prior observations of impaired early innate immune responses to primary infection such as influenza in ER mice. PMID- 26876763 TI - The impact of nutrients on the aging rate: A complex interaction of demographic, environmental and genetic factors. AB - Nutrition has a strong influence on the health status of the elderly, with many dietary components associated to either an increased risk of disease or to an improvement of the quality of life and to a delay of age-related pathologies. A direct effect of a reduced caloric intake on the delay of aging phenotypes is documented in several organisms. The role of nutrients in the regulation of human lifespan is not easy to disentangle, influenced by a complex interaction of nutrition with environmental and genetic factors. The individual genetic background is fundamental for mediating the effects of nutritional components on aging. Classical genetic factors able to influence nutrient metabolism are considered those belonging to insulin/insulin growth factor (INS/IGF-1) signaling, TOR signaling and Sirtuins, but also genes involved in inflammatory/immune response and antioxidant activity can have a major role. Considering the worldwide increasing interest in nutrition to prevent age related diseases and achieve a healthy aging, in this review we will discuss this complex interaction, in the light of metabolic changes occurring with aging, with the aim of shedding a light on the enormous complexity of the metabolic scenario underlying longevity phenotype. PMID- 26876762 TI - Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921. AB - Telomere length is hypothesised to be a biological marker of both cognitive and physical ageing. Here we measure telomere length, and cognitive and physical abilities at mean ages 70, 73 and 76 years in the Lothian Birth Cohort 1936 (LBC1936), and at mean ages 79, 87, 90 and 92 years in the Lothian Birth Cohort 1921 (LBC1921). We investigate whether telomere length change predicts change in cognitive and physical abilities. In LBC1936 telomere length decreased by an average of 65 base pairs per year and in LBC1921 by 69 base pairs per year. However, change in telomere length did not predict change in cognitive or physical abilities. This study shows that, although cognitive ability, walking speed, lung function and grip strength all decline with age, they do so independently of telomere length shortening. PMID- 26876764 TI - Impact of the digital revolution on the future of pharmaceutical formulation science. AB - The ongoing digital revolution is no longer limited to the application of apps on the smart phone for daily needs but starts to affect also our professional life in formulation science. The software platform F-CAD (Formulation-Computer Aided Design) of CINCAP can be used to develop and test in silico capsule and tablet formulations. Such an approach allows the pharmaceutical industry to adopt the workflow of the automotive and aircraft industry. Thus, the first prototype of the drug delivery vehicle is prepared virtually by mimicking the composition (particle size distribution of the active drug substance and of the excipients within the tablet) and the process such as direct compression to obtain a defined porosity. The software is based on a cellular automaton (CA) process mimicking the dissolution profile of the capsule or tablet formulation. To take account of the type of dissolution equipment and all SOPs (Standard Operation Procedures) such as a single punch press to manufacture the tablet, a calibration of the F CAD dissolution profile of the virtual tablet is needed. Thus, the virtual tablet becomes a copy of the real tablet. This statement is valid for all tablets manufactured within the same formulation design space. For this reason, it is important to define already for Clinical Phase I the formulation design space and to work only within this formulation design space consisting of the composition and the processes during all the Clinical Phases. Thus, it is not recommended to start with a simple capsule formulation as service dosage form and to change later to a market ready tablet formulation. The availability of F-CAD is a necessary, but not a sufficient condition to implement the workflow of the automotive and aircraft industry for developing and testing drug delivery vehicles. For a successful implementation of the new workflow, a harmonization of the equipment and the processes between the development and manufacturing departments is a must. In this context, the clinical samples for Clinical Phases I and II should be prepared with a mechanical simulator of the high-speed rotary press used for large batches for Clinical Phases III & IV. If not, the problem of working practically and virtually in different formulation design spaces will remain causing worldwide annually billion of $ losses according to the study of Benson and MacCabe. The harmonization of equipment and processes needs a close cooperation between the industrial pharmacist and the pharmaceutical engineer. In addition, Virtual Equipment Simulators (VESs) of small and large scale equipment for training and computer assisted scale-up would be desirable. A lean and intelligent management information and documentation system will improve the connectivity between the different work stations. Thus, in future, it may be possible to rent at low costs F-CAD as an IT (Information Technology) platform based on a cloud computing solution. By the adoption of the workflow of the automotive and aircraft industry significant savings, a reduced time to market, a lower attrition rate, and a much higher quality of the final marketed dosage form can be achieved. PMID- 26876765 TI - The nurse practitioner-client therapeutic encounter: an integrative review of interaction in aged and primary care settings. AB - AIMS: To review the key features of the nurse practitioner-client interaction in the thera-peutic encounter to inform the development of nurse practitioner-led memory clinics. BACKGROUND: Nurse practitioners spend significant time interacting with clients and their families/caregivers yet there is limited research on this interaction during therapeutic encounters in aged and primary care contexts. DESIGN: Integrative review. DATA SOURCES: Electronic search of CINAHL, Embase, Medline, PsychINFO, PubMed, Scopus, Web of Science 2004-2013; hand search of the Journal of Advanced Nursing, Journal of the American Academy of Nurse Practitioners and Journal of Clinical Nursing. REVIEW METHODS: Integrative literature review using Whittemore and Knafl's methodology. RESULTS: Ten published studies were included, representing over 900 nurse practitioners and their clients. Three key factors of nurse practitioner-client interaction were identified: nurse practitioner expertise and the influence of the therapeutic encounter context; affirming exchange as a bedrock of communication; and high levels of client engagement. In aged and primary care settings, where the therapeutic encounter requires and allows longer consultations, such as nurse practitioner-led memory clinics, patient-centred approaches can engage clients in consultations using a biopsychosocial framework, resulting in improved client satisfaction and, potentially, increased adherence to treatment plans. Nurse practitioners who are open and respectful, who encourage patients to provide more information about their lives and condition and are perceived by the client to be empathetic, are providing affirmation to the client. CONCLUSION: Affirming interactions are a key feature of successful therapeutic encounters when time and context do not allow or warrant the full repertoire of patient-centred communication. PMID- 26876766 TI - Parietal and occipital encephalocele in same child: A rarest variety of double encephalocele. AB - An encephalocele is a protrusion of the brain and/or meninges through a defect in the skull. Based on the location of the skull defect they are classified into sincipital, basal, occipital or parietal varieties. Occurrence of more than one Encephalocele in a patient is very rare and very few cases of double encephalocele are reported. We report an interesting case where a parietal and an occipital encephalocele were present together. The patient was a 2 months boy who was brought to us with complaints of two swelling on the scalp since birth. Neuroimaging studies confirmed it to be a case of double encephalocele. The rarity of the findings prompted us to report this case. The presentation and management of the case along with and review of the relevant literature is presented. PMID- 26876767 TI - Expanding phenotype of PRRT2 gene mutations: A new case with epilepsy and benign myoclonus of early infancy. AB - BACKGROUND: Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early infancy have not been reported. CLINICAL REPORT: We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. DISCUSSION: We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. CONCLUSIONS: Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders. PMID- 26876768 TI - Safety of levetiracetam among infants younger than 12 months--Results from a European multicenter observational study. AB - BACKGROUND: There are limited data on the use of the antiepileptic drug (AED) levetiracetam for the treatment of infants. AIM: To prospectively evaluate the safety of levetiracetam oral solution and its impact on epilepsy severity in infants with different seizure types. METHODS: This noninterventional post authorization safety study included patients 1-11 months of age. Patients' treatment - levetiracetam dose, and addition, withdrawal or changes in the doses of concomitant medications and AEDs - was at the discretion of the physician. The primary variable was treatment-emergent adverse events (TEAEs). RESULTS: Of 101 infants, 75 completed and 26 discontinued the study. Mean age was 6.0 months, 50 were male, most (80%) took 1 >= concomitant AED and had cryptogenic or symptomatic epilepsy that was focal (38.6%) or generalized (20.8%), particularly frontal lobe epilepsy (20.0%) or West syndrome/infantile spasms (20.0%). Among known aetiologies, congenital factors (22.8%) such as dysplastic lesions or perinatal events (17.8%) were predominant. Overall, 54.5% of patients had >= 1 TEAE. Five patients experienced drug-related TEAEs - convulsion, irritability, somnolence and hypotonia, all listed in the product label, with the exception of hypotonia, which was reported for one patient and resolved without any change in study medication. Seven patients discontinued due to TEAEs, mainly due to infantile spasms and respiratory disorders. At study end, 71.8% of patients showed improvement in epilepsy severity, 18.8% remained stable and 9.4% showed worsening. Levetiracetam did not appear to have a negative effect on growth parameters. CONCLUSION: In this prospective study, which included the largest number of patients in this age range so far, levetiracetam was found to be well tolerated and efficacious for the treatment of infants with epilepsy. PMID- 26876769 TI - Long-term motor, cognitive and behavioral outcome of acute disseminated encephalomyelitis. AB - OBJECTIVE: The purpose of this study was to evaluate the long-term motor and neurocognitive outcome of children with acute disseminated encephalomyelitis and to identify prognostic risk factors. METHODS: The study included 43 children who were hospitalized due to acute disseminated encephalomyelitis during the years 2002-2012. The children underwent full neurological examinations, along with comprehensive neurocognitive and behavioral assessments. RESULTS: Twenty-six (61%) children had different degrees of neurological sequelae after a mean follow up of 5.5 +/- 3.5 years. The most common residual impairment included attention deficit hyperactivity disorder (44%), behavioral problems (32%), and learning disabilities (21%). Five (12%) children had a full-scale IQ of 70 or less, compared to 2.2% in the general population. CONCLUSIONS: Neurocognitive sequelae were found even in children who were considered as fully recovered at the time of discharge. Risk factors for severe neurological sequelae were older age at diagnosis and male gender. We suggest neuropsychological testing and long-term follow-up for all children with acute disseminated encephalomyelitis, even in the absence of neurological deficits at discharge. PMID- 26876770 TI - Neutrophil extracellular Taps play an important role in clearance of Streptococcus suis in vivo. AB - Streptococcus suis infection induces formation of neutrophil extracellular traps (NETs) in vitro; however, the contribution of NETs-mediated killing to the pathogenesis of S. suis in vivo is yet to be elicited. The findings of the present study indicated that extracellular DNA fiber can be induced in a murine model in response to S. suis infection. A nuclease that destroys their structure was used to evaluate the role of NETs on S. suis infection. Treatment with nuclease resulted in a greater bacteria load and higher serum TNF-alpha concentrations in response to S. suis infection, indicating that NETs structure played an essential role in S. suis clearance and inflammation. Furthermore, nuclease treatment resulted in more severe clinical signs during and higher mortality from S. suis infection. These findings indicated that NETs structure contributes to protection against S. suis infection. PMID- 26876771 TI - Sensitizing Future Health Professionals to Determinants of Childhood Obesity. AB - Long-term solutions to the childhood obesity epidemic will require concerted interdisciplinary efforts that are sensitive to both individual and social determinants of health. The Junior Doctors of Health(c) (JDOH) program involves interprofessional education (IPE) with university students from health science fields (e.g., medicine, pharmacy, social work, public health) who deliver an interactive program in teams to at-risk school-aged youth. The purpose of this study was to assess the impact of participation in the JDOH IPE program on university students' beliefs about childhood obesity. Fifty-three of the 71 health sciences students enrolled in the JDOH IPE program between 2011 and 2013 participated in this study. Pre- and post-surveys assessed students' beliefs about the importance, causes of, and responsibility for reducing childhood obesity with both closed- and open-ended questions. In 2013, quantitative data were analyzed using Wilcoxon matched-pairs signed-rank tests and qualitative data were analyzed through open coding to identify emergent themes. Results indicate that after participation in the JDOH IPE program, students' identification of social and environmental causes of childhood obesity increased significantly. Further, students' ranking of the importance of obesity was initially higher than those of different issues typically portrayed as social or environmental (e.g., youth violence) but it was similarly ranked after participation in JDOH. This suggests a greater sensitivity to social and environmental challenges faced by youth. Findings suggest that IPE experiences that bring clinical and community oriented health professions together to engage with disadvantaged youth foster sensitivity to the complexities of childhood obesity in low-income settings. PMID- 26876773 TI - Spontaneous cooperation for prosocials, but not for proselfs: Social value orientation moderates spontaneous cooperation behavior. AB - Cooperation is essential for the success of societies and there is an ongoing debate whether individuals have therefore developed a general spontaneous tendency to cooperate or not. Findings that cooperative behavior is related to shorter decision times provide support for the spontaneous cooperation effect, although contrary results have also been reported. We show that cooperative behavior is better described as person * situation interaction, in that there is a spontaneous cooperation effect for prosocial but not for proself persons. In three studies, one involving population representative samples from the US and Germany, we found that cooperation in a public good game is dependent on an interaction between individuals' social value orientation and decision time. Increasing deliberation about the dilemma situation does not affect persons that are selfish to begin with, but it is related to decreasing cooperation for prosocial persons that gain positive utility from outcomes of others and score high on the related general personality trait honesty/humility. Our results demonstrate that the spontaneous cooperation hypothesis has to be qualified in that it is limited to persons with a specific personality and social values. Furthermore, they allow reconciling conflicting previous findings by identifying an important moderator for the effect. PMID- 26876772 TI - Revisiting the Rise of Electronic Nicotine Delivery Systems Using Search Query Surveillance. AB - INTRODUCTION: Public perceptions of electronic nicotine delivery systems (ENDS) remain poorly understood because surveys are too costly to regularly implement and, when implemented, there are long delays between data collection and dissemination. Search query surveillance has bridged some of these gaps. Herein, ENDS' popularity in the U.S. is reassessed using Google searches. METHODS: ENDS searches originating in the U.S. from January 2009 through January 2015 were disaggregated by terms focused on e-cigarette (e.g., e-cig) versus vaping (e.g., vapers); their geolocation (e.g., state); the aggregate tobacco control measures corresponding to their geolocation (e.g., clean indoor air laws); and by terms that indicated the searcher's potential interest (e.g., buy e-cigs likely indicates shopping)-all analyzed in 2015. RESULTS: ENDS searches are rapidly increasing in the U.S., with 8,498,000 searches during 2014 alone. Increasingly, searches are shifting from e-cigarette- to vaping-focused terms, especially in coastal states and states where anti-smoking norms are stronger. For example, nationally, e-cigarette searches declined 9% (95% CI=1%, 16%) during 2014 compared with 2013, whereas vaping searches increased 136% (95% CI=97%, 186%), even surpassing e-cigarette searches. Additionally, the percentage of ENDS searches related to shopping (e.g., vape shop) nearly doubled in 2014, whereas searches related to health concerns (e.g., vaping risks) or cessation (e.g., quit smoking with e-cigs) were rare and declined in 2014. CONCLUSIONS: ENDS popularity is rapidly growing and evolving. These findings could inform survey questionnaire development for follow-up investigation and immediately guide policy debates about how the public perceives the health risks or cessation benefits of ENDS. PMID- 26876774 TI - Corrigendum: Irisin promotes osteoblast proliferation and differentiation via activating the MAP kinase signaling pathways. PMID- 26876775 TI - Effects of operational parameters on dark fermentative hydrogen production from biodegradable complex waste biomass. AB - This work aimed to investigate the effect of the initial pH, combination of food to microorganism ratio (F/M) and initial pH, substrate pre-treatment and different inoculum sources on the dark fermentative biohydrogen (H2) yields. Three model complex waste biomasses (food waste, olive mill wastewater (OMWW) and rice straw) were used to assess the effect of the aforementioned parameters. The effect of the initial pH between 4.5 and 7.0 was investigated in batch tests carried out with food waste. The highest H2 yields were shown at initial pH 4.5 (60.6 +/- 9.0 mL H2/g VS) and pH 5.0 (50.7 +/- 0.8 mL H2/g VS). Furthermore, tests carried out with F/M ratios of 0.5, 1.0 and 1.5 at initial pH 5.0 and 6.5 revealed that a lower F/M ratio (0.5 and 1.0) favored the H2 production at an initial pH 5.0 compared to pH 6.5. Alkaline pre-treatment of raw rice straw using 4% and 8% NaOH at 55 degrees C for 24h, increased the H2 yield by 26 and 57-fold, respectively. In the dark fermentation of OMWW, the H2 yield was doubled when heat-shock pre-treated activated sludge was used as inoculum in comparison to anaerobic sludge. Overall, this study shows that the application of different operating parameters to maximize the H2 yields strongly depends on the biodegradability of the substrate. PMID- 26876776 TI - Stabilization/solidification of lead in MSWI fly ash with mercapto functionalized dendrimer Chelator. AB - This work compares the performance of stabilizing Pb by Sodium sulfide (Na2S), Sodium phosphate (Na3PO4), thiourea (H2NCSNH2), and mercapto functionalized dendrimer (TEPA-SNa) in MSWI fly ash, including leaching toxicity analysis and leaching behavior analysis, as a function of pH. The leaching toxicity in fly ash indicated that leaching value of Pb stabilized by Na2S, Na3PO4, and H2NCSNH2 has remained higher than the limit value (0.25mg/L) with a dosage of 10%. However, the leaching value associated with TEPA-SNa approaches zero at a dosage of 3%. The effective leaching test results showed the leaching amount of Pb stabilized by TEPA-SNa with a dosage of 3% to be 3.58 mg/kg less than the maximum allowable amount of leaching (5mg/kg), but the amount of Pb leached by Na2S, Na3PO4, and H2NCSNH2 was much higher than 5mg/kg. The leaching behavior of Pb as a function of pH showed that the leaching concentration of Pb stabilized by TEPA-SNa can approach zero at a dosage of 5% no matter how the pH changes. In summary, TEPA SNa can interact with Pb(2+) in the acid-base environment and effectively immobilize Pb(2+) in fly ash in the long term. PMID- 26876777 TI - Preliminary investigation on the thermal conversion of automotive shredder residue into value-added products: Graphitic carbon and nano-ceramics. AB - Large increasing production volumes of automotive shredder residue (ASR) and its hazardous content have raised concerns worldwide. ASR has a desirable calorific value, making its pyrolysis a possible, environmentally friendly and economically viable solution. The present work focuses on the pyrolysis of ASR at temperatures between 950 and 1550 degrees C. Despite the high temperatures, the energy consumption can be minimized as the decomposition of ASR can be completed within a short time. In this study, the composition of ASR was investigated. ASR was found to contain about 3% Ti and plastics of high calorific value such as polypropylene, polyethylene, polycarbonate and polyurethane. Based on thermogravimetric analysis (TGA) of ASR, the non-isothermal degradation kinetic parameters were determined using Coats-Redfern's and Freeman and Carroll methods. The evolved gas analysis indicated that the CH4 was consumed by the reduction of some oxides in ASR. The reduction reactions and the presence of Ti, silicates, C and N in ASR at 1550 degrees C favor the formation of specific ceramics such as TiN and SiC. The presence of nano-ceramics along with a highly-crystalline graphitic carbon in the pyrolysis residues obtained at 1550 degrees C was confirmed by scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and Raman imaging microscope (RIM) analyses. PMID- 26876778 TI - Sensitivity-to-change and validity of semi-automatic joint space width measurements in hand osteoarthritis: a follow-up study. AB - OBJECTIVE: To assess sensitivity-to-change and validity of longitudinal quantitative semi-automatic joint space width (JSW) measurements and to compare this method with semi-quantitative joint space narrowing (JSN) scoring in hand osteoarthritis (OA) patients. DESIGN: Baseline and 2-year follow-up radiographs of 56 hand OA patients (mean age 62 years, 86% women) were used. JSN was scored 0 3 using the Osteoarthritis Research Society International atlas and JSW was quantified in millimetres (mm) in the second to fifth distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs, MCPJs). Sensitivity-to change was evaluated by calculating Standardized Response Means (SRMs). Change in JSW or JSN above the Smallest Detectable Difference (SDD) defined progression on joint level. To assess construct validity, progressed joints were compared by cross-tabulation and by associating baseline ultrasound variables with progression (using generalized estimating equations, adjusting for age and sex). RESULTS: The JSW method detected statistically significant mean changes over 2.6 years (-0.027 mm (95%CI -0.01; -0.04), -0.024 mm (-0.01; -0.03), -0.021 mm ( 0.01; -0.03) for DIPJs, PIPJs, MCPJs, respectively). Sensitivity-to-change was low (SRMs: 0.174, 0.168, 0.211, respectively). 9.1% (121/1336) of joints progressed in JSW, but 3.6% (48/1336) widened. 83 (6.2%) joints progressed in JSW only, 36 (2.7%) in JSN only and 37 (2.8%) in both methods. Progression in JSW showed weaker associations with baseline inflammatory ultrasound features than progression in JSN. CONCLUSIONS: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements in hand OA clinical trials remains questionable. PMID- 26876779 TI - Lateral habenula integration of proactive and retroactive information mediates behavioral flexibility. AB - The lateral habenula (LHb) is known to play an important role in signaling aversive or adverse events that have happened or are predicted by cues under Pavlovian conditions. In rodents, it is also required for behavioral flexibility when changes in reward outcomes signal that strategies should be changed. It is not known whether the LHb also controls appetitive behaviors when an animal is able to utilize external cues proactively to guide upcoming decisions. In order to test this, male Long-Evans rats were trained to switch between two arms of a figure eight maze based on the tone presented prior to the choice. Importantly, the tones were switched every three to six trials so rats were able establish a response pattern before being required to switch. This caused rats to rely on both proactive (tones) and retroactive information (reward feedback) to guide behavior. Inactivation of the LHb with the GABA agonists baclofen and muscimol impaired overall performance by increasing both errors when the tones are switched (switch errors) as well as on subsequent trials (perseverative errors) indicating that both proactive and retroactive information are utilized by the LHb to guide behavioral flexibility. Once a correct choice was made in a given block, LHb inactivated rats did not make more errors than controls. A control study revealed that the LHb is not required for tone or reward magnitude discrimination per se. These results demonstrate for the first time that the LHb contributes to behavioral flexibility through utilizing both proactive and retroactive information when performing appetitive tasks. PMID- 26876780 TI - Spectral variation of fluorescence lifetime near single metal nanoparticles. AB - We explore the spectral dependence of fluorescence enhancement and the associated lifetime modification of fluorescent molecules coupled to single metal nanoparticles. Fluorescence lifetime imaging microscopy and single-particle dark field spectroscopy are combined to correlate the dependence of fluorescence lifetime reduction on the spectral overlap between the fluorescence emission and the localised surface plasmon (LSP) spectra of individual gold nanoparticles. A maximum lifetime reduction is observed when the fluorescence and LSP resonances coincide, with good agreement provided by numerical simulations. The explicit comparison between experiment and simulation, that we obtain, offers an insight into the spectral engineering of LSP mediated fluorescence and may lead to optimized application in sensing and biomedicine. PMID- 26876781 TI - Exploring interactions between pathogens and the Drosophila gut. AB - Gastrointestinal infection can provoke substantial disturbance at both a local as well as at a systemic level and may evolve into a chronic disease state. Our growing knowledge of gut-pathogen interactions has been based to a large extent on the use of genetically tractable model hosts such as the fruit fly Drosophila melanogaster. In this review we will summarise the growing literature and critically address the advantages and disadvantages of using this model to extrapolate results from studying pathogen virulence and intestinal responses to humans. PMID- 26876782 TI - Tungiasis in Italy: An imported case of Tunga penetrans and review of the literature. AB - Tungiasis is an animal and human parasitic disease caused by fleas of the genus Tunga (Siphonaptera, Tungidae), endemic in equatorial and subtropical regions and rarely described in European countries, where clinicians and general pathologists could be not aware of this parasitic disease. To our knowledge, only 75 cases of human tungiasis (not all described in detail) were previously reported in Italy. We described a new case in a 34-year-old Italian flight attendant who developed a granuloma-like, ulcerated nodule in the subungual region of his left 5th toe, partially detaching the nail, about 20-30 days after his return from Brazil. We performed a detailed review of the literature of the Italian cases, suggesting the use of histochemical stains (especially Trichrome stain) in order to underline parasitic details. Tourism in endemic regions and globalization may result in new cases in developed countries and previously unaffected regions, therefore pathologists should consider this parasitic disease. PMID- 26876783 TI - Liposomal nanocarriers for plasminogen activators. AB - Several plasminogen activators (PAs) have been found effective in treating different thromboembolic diseases. However, administration of conventional thrombolytic therapy is limited by a low efficacy of present formulations of PAs. Conventional treatments using these therapeutic proteins are associated with several limitations including rapid inactivation and clearance, short half-life, bleeding complications or non-specific tissue targeting. Liposome-based formulations of PAs such as streptokinase, tissue-plasminogen activator and urokinase have been developed to improve the therapeutic efficacy of these proteins. Resulting liposomal formulations were found to preserve the original activity of PAs, promote their selective delivery and improve thrombus targeting. Therapeutic potential of these liposome-based PAs has been demonstrated successfully in various pre-clinical models in vivo. Reductions in unwanted side effects (e.g., hemorrhage or immunogenicity) as well as enhancements of efficacy and safety were achieved in comparison to currently existing treatment options based on conventional formulations of PAs. This review summarizes present achievements in: (i) preparation of liposome-based formulations of various PAs, (ii) development of PEGylated and targeted liposomal PAs, (iii) physico-chemical characterization of these developed systems, and (iv) testing of their thrombolytic efficacy. We also look to the future and the imminent arrival of theranostic liposomal formulations to move this field forward. PMID- 26876784 TI - Perioperative blood ordering optimization process using information from an anesthesia information management system. AB - BACKGROUND: As part of ongoing perioperative surgical home implantation process, we applied a previously published algorithm for creation of a maximum surgical blood order schedule (MSBOS) to our operating rooms. We hypothesized that using the MSBOS we could show a reduction in unnecessary preoperative blood testing and associated costs. STUDY DESIGN AND METHODS: Data regarding all surgical cases done at UC Irvine Health's operating rooms from January 1, 2011, to January 1, 2014 were extracted from the anesthesia information management systems (AIMS). After the data were organized into surgical specialties and operative sites, blood order recommendations were generated based on five specific case characteristics of the group. Next, we assessed current ordering practices in comparison to actual blood utilization to identify potential areas of wastage and performed a cost analysis comparing the annual hospital costs from preoperative blood orders if the blood order schedule were to be followed to historical practices. RESULTS: Of the 19,138 patients who were categorized by the MSBOS as needing no blood sample, 2694 (14.0%) had a type and screen (T/S) ordered and 1116 (5.8%) had a type and crossmatch ordered. Of the 6073 procedures where MSBOS recommended only a T/S, 2355 (38.8%) had blood crossmatched. The cost analysis demonstrated an annual reduction in actual hospital costs of $57,335 with the MSBOS compared to historical blood ordering practices. CONCLUSION: We showed that the algorithm for development of a multispecialty blood order schedule is transferable and yielded reductions in preoperative blood product screening at our institution. PMID- 26876785 TI - Corrigendum: Basolateral amygdala rapid glutamate release encodes an outcome specific representation vital for reward-predictive cues to selectively invigorate reward-seeking actions. PMID- 26876786 TI - Histone deacetylase inhibitors suppress mutant p53 transcription via HDAC8/YY1 signals in triple negative breast cancer cells. AB - There is an urgent need to investigate the potential targeted therapy approach for triple-negative breast cancer (TNBC). Our present study reveals that histone deacetylase inhibitors (HDACIs) suberoyl anilide hydroxamic acid (SAHA) and sodium butyrate (NaB) significantly inhibit cell proliferation, arrest cell cycle at G0/G1 phase, and induce mitochondrial related apoptosis of TNBC cells. Further, SAHA and NaB decrease the phosphorylation, protein and mRNA levels of mutant p53 (mtp53) in TNBC cells. While SAHA or NaB has no similar inhibition effect on wild type p53 (wtp53). The inhibition apparently occurs at the level of transcription because the down regulation of precursor p53 transcription is much more rapid (less than 2h) and sharp than that of mature p53. The knockdown of HDAC8, while not HDAC6, inhibits the transcription of mtp53 in TNBC cells. The luciferase assay and ChIP analysis reveal that both SAHA and NaB can reduce the binding of transcription factor Yin Yang 1 (YY1) with the -102 to -96 position of human p53 promoter. Knockdown of YY1 also significantly inhibits the transcription of mtp53 in TNBC cells. Further, SAHA and NaB can inhibit the association of HDAC8 and YY1, increase acetylation of residues 170-200 of YY1, then decrease its transcription activities, and finally suppress YY1 induced p53 transcription. Together, our data establish that SAHA and NaB can be considered as drug candidates for TNBC patients, and HDAC8/YY1/mtp53 signals act as an important target for TNBC treatment. PMID- 26876787 TI - Extracellular-signal regulated kinase (Erk1/2), mitogen-activated protein kinase activated protein kinase 2 (MK2) and tristetraprolin (TTP) comprehensively regulate injury-induced immediate early gene (IEG) response in in vitro liver organ culture. AB - Differentiated hepatocytes are long-lived and normally do not undergo cell division, however they have the unique capacity to autonomously decide their replication fate after liver injury. In this context, the key players of liver regeneration immediately after injury have not been adequately studied. Using an in vitro liver culture system, we show that after liver injury, p38 mitogen activated protein kinase (p38MAPK), mitogen-activated protein kinase-activated protein kinase 2 (MK2) and extracellular-signal regulated kinase (Erk)1/2 were activated within 15 min and continued to be phosphorylated for more than 2h. Both p38MAPK and Erk1/2 were activated at the edge of the cut as well as on the liver surface where the mesothelial cell sheet expresses several cytokines. Notably, in human liver Erk1/2 was also activated under the mesothelial cell sheet shortly after liver resections. Furthermore, in in vitro liver slice culture immediate early genes (IEGs) were upregulated within 1-2 h and the S phase marker proliferation-cell-nuclear-antigen (PCNA) appeared 24 h after injury. Although Erk1/2 was activated after injury, in MK2 depleted liver a set of IEGs, such as Dusp1, Cox2, or c-Myc and proliferation marker gene Ki67 were not induced. In addition, in immortalized hepatocyte cells, THLE-2, the same subset of genes was upregulated upon stimulation with lipopolysaccharide (LPS), but not in the presence of MK2 inhibitor. The protein level of tristetraprolin (TTP), a substrate for MK2 that plays a role in mRNA degradation, was increased in the presence of MK2 inhibitor. In this context, the depletion of TTP gene rescued Dusp1, Cox2, or c-Myc upregulation in the presence of MK2 inhibitor. These data imply that MK2 pathway is positively involved in Erk1/2 induced IEG response after liver injury. These data also suggest that in vitro liver culture may be a useful tool for measuring the proliferation potential of hepatocytes in individual liver. PMID- 26876788 TI - pH sensitive coiled coils: a strategy for enhanced liposomal drug delivery. AB - Stimuli responsive controlled release from liposome based vesicles is a promising strategy for the site specific delivery of drugs. Herein, we report the design of pH sensitive coiled coils and their incorporation into the liposome as triggers for the controlled release of encapsulated drugs. The designed coiled coil peptides with the incorporation of environment sensitive fluorescent amino acids were found to be stable at physiological pH and unstructured while changing the pH of the environment to either acidic or basic. This pH dependent conformational switch of the coiled-coil polypeptides was exploited as triggers for the enhanced release of the encapsulated drug molecules from liposomes. The SEM, DLS and TEM analysis revealed the uniform morphology of the peptide liposome hybrid vesicles. Further, the drug encapsulated liposome internalization experiments with cancer cells revealed the enhanced release and accumulation of drugs in the acidic lysosomal compartments in comparison with liposomes without coiled coils. PMID- 26876789 TI - Simulation shows that HLA-matched stem cell donors can remain unidentified in donor searches. AB - The heterogeneous nature of HLA information in real-life stem cell donor registries may hamper unrelated donor searches. It is even possible that fully HLA-matched donors with incomplete HLA information are not identified. In our simulation study, we estimated the probability of these unnecessarily failed donor searches. For that purpose, we carried out donor searches in several virtual donor registries. The registries differed by size, composition with respect to HLA typing levels, and genetic diversity. When up to three virtual HLA typing requests were allowed within donor searches, the share of unnecessarily failed donor searches ranged from 1.19% to 4.13%, thus indicating that non identification of completely HLA-matched stem cell donors is a problem of practical relevance. The following donor registry characteristics were positively correlated with the share of unnecessarily failed donor searches: large registry size, high genetic diversity, and, most strongly correlated, large fraction of registered donors with incomplete HLA typing. Increasing the number of virtual HLA typing requests within donor searches up to ten had a smaller effect. It follows that the problem of donor non-identification can be substantially reduced by complete high-resolution HLA typing of potential donors. PMID- 26876790 TI - Cell therapy licensing: a web for the unwary in Kimble v. Marvel Entertainment? PMID- 26876791 TI - Don't Be a One-Trick Pony. PMID- 26876792 TI - Directed block copolymer self-assembly implemented via surface-embedded electrets. AB - Block copolymer (BCP) nanolithography is widely recognized as a promising complementary approach to circumvent the feature size limits of conventional photolithography. The directed self-assembly of BCP thin film to form ordered nanostructures with controlled orientation and localized pattern has been the key challenge for practical nanolithography applications. Here we show that BCP nanopatterns can be directed on localized surface electrets defined by electron beam irradiation to realize diverse features in a simple, effective and non destructive manner. Charged electrets can generate a built-in electric field in BCP thin film and induce the formation of perpendicularly oriented microdomain of BCP film. The electret-directed orientation control of BCP film can be either integrated with mask-based patterning technique or realized by electron-beam direct-writing method to fabricate microscale arbitrary lateral patterns down to single BCP cylinder nanopattern. The electret-directed BCP self-assembly could provide an alternative means for BCP-based nanolithography, with high resolution. PMID- 26876793 TI - Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume. AB - OBJECTIVES: To investigate the influence of metabolic syndrome on prostate specific antigen levels by considering prostate volume and plasma volume. METHODS: We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen * plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. RESULTS: Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 +/- 0.91 vs 1.15 +/- 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 +/- 0.084 vs 0.115 +/- 0.071 MUg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate specific antigen decrease by 4.1%, P = 0.046). CONCLUSIONS: Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume. PMID- 26876794 TI - The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. AB - The incretin effect describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals. This effect, which is uniformly defective in patients with type 2 diabetes, is mediated by the gut derived incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The importance of the incretin effect for the maintenance of glucose homoeostasis is clearly established, and incretin-based therapies are among the most promising new therapies for type 2 diabetes. However, despite the effectiveness of these therapies in many patients, the idea that they restore the incretin effect is a common misconception. In type 2 diabetes, the endocrine pancreas remains responsive to GLP-1 but is no longer responsive to GIP, which is the most likely reason for a reduced or absent incretin effect. Incretin-based drugs, including GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, stimulate GLP-1 receptors and thus augment insulin secretion in response to both oral and intravenous glucose stimulation, thereby abolishing any potential difference in the responses to these stimuli. These drugs therefore do not restore the defective incretin effect in patients. By contrast, some bariatric surgical procedures enhance GLP-1 responses and also restore the incretin effect in obese individuals with type 2 diabetes. Thus, not all biological actions elicited by the stimulation of GLP-1 receptors lead to quantitative changes to the incretin effect. PMID- 26876795 TI - Metabolic disorders: how can systems modelling help? PMID- 26876796 TI - Occam's Quantum Strop: Synchronizing and Compressing Classical Cryptic Processes via a Quantum Channel. AB - A stochastic process' statistical complexity stands out as a fundamental property: the minimum information required to synchronize one process generator to another. How much information is required, though, when synchronizing over a quantum channel? Recent work demonstrated that representing causal similarity as quantum state-indistinguishability provides a quantum advantage. We generalize this to synchronization and offer a sequence of constructions that exploit extended causal structures, finding substantial increase of the quantum advantage. We demonstrate that maximum compression is determined by the process' cryptic order--a classical, topological property closely allied to Markov order, itself a measure of historical dependence. We introduce an efficient algorithm that computes the quantum advantage and close noting that the advantage comes at a cost-one trades off prediction for generation complexity. PMID- 26876797 TI - Ac-susceptibility investigations of superspin blocking and freezing in interacting magnetic nanoparticle ensembles. AB - We have investigated the effect of dipolar interactions on the superspin blocking and freezing of 9 nm average size Fe3O4 magnetic nanoparticle ensembles. Our dynamic susceptibility data reveals a two-regime behavior of the blocking temperature, T(B), upon diluting a Fe3O4/hexane magnetic fluid. As the nanoparticle volume ratio, Phi, is reduced from an as-prepared reference Phi = 1 to Phi = 1/96, the blocking temperature decreases from 46.1 K to 34.2 K, but higher values reenter upon further diluting the magnetic fluid to Phi = 1/384 (where T(B) = 42.5 K). We found evidence that cooling below T B within the higher concentration range (Phi > 1/48) leads to the collective freezing of the superspins, whereas individual superspin blocking occurs in the presence of weaker interactions (Phi < 1/96). The unexpected increase of the blocking temperature with the decrease of the inter-particle interactions observed at low nanoparticle concentrations is well described by the Morup-Tronc model. PMID- 26876798 TI - Sarcopenia and survival in patients undergoing pancreatic resection. AB - BACKGROUND: Recent studies have suggested that lean core muscle area may predict outcomes from major abdominal surgeries. Pancreatic resections have been independently analyzed less frequently. METHODS: Pancreatic resections from 2005 to 2012 were reviewed. Sarcopenia was defined as the lowest tertile for lean psoas muscle area (LPMA). Preoperative risk factors, including comorbidities, albumin, weight loss, age and gender, were analyzed with a primary endpoint of overall survival. Secondary endpoints included complications, discharge destination and readmission. RESULTS: The study sample of 270 patients had complications in 42% of patients, with 26% developing serious complication. The majority (80%) were discharged home, and 1.9% died in the peri-operative period. The mean length of follow up was 31.2 months (range 0-94), and 37% required at least one readmission. LPMA was predictive of discharge destination for females (p = 0.038). Sarcopenia was predictive of readmission in males, compared to subjects in the second LPMA tertile (HR 0.3; 95% CI: 0.1-0.9). In all male subjects, including a subset with adenocarcinoma, patients with sarcopenia were more likely to die than males in the highest LPMA tertile (HR: 2.6; 95% CI: 1.4 4.8 and HR: 2.4; 95% CI: 1.2-4.9, respectively). In all patients with pancreatic ductal adenocarcinoma, transfusion (HR: 1.9; 95% CI: 1.1-3.4) and positive margins (HR: 2.0; 95% CI: 1.2-3.3) were the only factors predictive of overall survival. CONCLUSIONS: Sarcopenia appears to be a predictor of overall survival in male patients undergoing pancreatic resections, but not specifically for patients with pancreatic ductal adenocarcinoma. As prospective data in future studies are identified, sarcopenia may become a useful tool in predicting outcomes. PMID- 26876799 TI - Automated spectrophotometric bicarbonate analysis in duodenal juice compared to the back titration method. AB - OBJECTIVES: We have recently evaluated a short endoscopic secretin test for exocrine pancreatic function. Bicarbonate concentration in duodenal juice is an important parameter in this test. Measurement of bicarbonate by back titration as the gold standard method is time consuming, expensive and technically difficult, thus a simplified method is warranted. We aimed to evaluate an automated spectrophotometric method in samples spanning the effective range of bicarbonate concentrations in duodenal juice. We also evaluated if freezing of samples before analyses would affect its results. METHODS: Patients routinely examined with short endoscopic secretin test suspected to have decreased pancreatic function of various reasons were included. Bicarbonate in duodenal juice was quantified by back titration and automatic spectrophotometry. Both fresh and thawed samples were analysed spectrophotometrically. RESULTS: 177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001) CONCLUSIONS: The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometrical analysis correlates excellent with the back titration gold standard. This is a major simplification of direct pancreas function testing, and allows a wider distribution of bicarbonate testing in duodenal juice. Extreme values for Bicarbonate concentration achieved by the autoanalyser method have to be interpreted with caution. PMID- 26876800 TI - Pharmacological therapies for infantile hemangiomas: A clinical study in 853 consecutive patients using a standard treatment algorithm. AB - Infantile hemangiomas are the most common infantile benign vascular tumor. While most infantile hemangiomas proliferate then involute, some may persist and require treatment for reasons including risk of disfigurement or functional impairment. Treatments currently include observation, pharmacological therapy, laser, cryosurgery, surgery and radiotherapy. Although pharmacological therapy is a well accepted treatment option, limited studies have evaluated the efficacy of different drug therapies. In this study, we compare different pharmacological modalities in the management of infantile hemangiomas. The study included 853 infants with proliferative infantile hemangiomas who were treated with topical timolol, oral propranolol, intralesional pingyangmycin, or intravenous vincristine from 2009 to 2012. Treatment stratification was based on clinical severity of the tumor. Response to the treatment was clinically evaluated and graded as: excellent, good, poor, or no response. Response to pharmacological therapies was excellent in almost all infantile hemangiomas. In addition, patients younger than 8 months responded highly to pharmacological treatment (89.1%), while patients older than 8 months were less responsive to treatment (36.3%). There were no instances of life-threatening complications. Overall, these findings support the efficacy of timolol, propranolol, pingyangmycin and vincristine in the treatment of infantile hemangiomas, especially in the youngest patient cohort (8 months or younger). PMID- 26876801 TI - Increasing Incidence of Degenerative Spinal Diseases in Japan during 25 Years: The Registration System of Spinal Surgery in Tohoku University Spine Society. AB - Spinal disorders affect mainly older people and cause pain, paralysis and/or deformities of the trunk and/or extremities, which could eventually disturb locomotive functions. For ensuring safe and high-quality treatment of spinal disorders, in 1987, the Tohoku University Spine Society (TUSS) was established by orthopedic departments in Tohoku University School of Medicine and its affiliated hospitals in and around Miyagi Prefecture. All spine surgeries have been enrolled in the TUSS Spine Registry since 1988. Using the data from this registration system between 1988 and 2012, we demonstrate here the longitudinal changes in surgical trends for spinal disorders in Japan that has rushed into the most advanced "aging society" in the world. In total, data on 56,744 surgeries were retrieved. The number of spinal surgeries has annually increased approximately 4 fold. There was a particular increase among patients aged >= 70 years and those aged >= 80 years, with a 20- to 90-fold increase. Nearly 90% of the spinal operations were performed for degenerative disorders, with their number increasing approximately 5-fold from 705 to 3,448. The most common disease for surgery was lumbar spinal stenosis (LSS) (35.9%), followed by lumbar disc herniation (27.7%) and cervical myelopathy (19.8%). In 2012, approximately half of the patients with LSS and cervical myelopathy were >= 70 years of age. In conclusion, the number of spinal operations markedly increased during the 25-year period, particularly among older patients. As Japan has a notably aged population, the present study could provide a near-future model for countries with aging population. PMID- 26876802 TI - Bio-nanocapsules displaying various immunoglobulins as an active targeting-based drug delivery system. AB - The bio-nanocapsule (BNC) is an approximately 30-nm particle comprising the hepatitis B virus (HBV) envelope L protein and a lipid bilayer. The L protein harbors the HBV-derived infection machinery; therefore, BNC can encapsulate payloads such as drugs, nucleic acids, and proteins and deliver them into human hepatocytes specifically in vitro and in vivo. To diversify the possible functions of BNC, we generated ZZ-BNC by replacing the domain indispensable for the human hepatotrophic property of BNC (N-terminal region of L protein) with the tandem form of the IgG Fc-binding Z domain of Staphylococcus aureus protein A. Thus, the ZZ-BNC is an active targeting-based drug delivery system (DDS) nanocarrier that depends on the specificity of the IgGs displayed. However, the Z domain limits the animal species and subtypes of IgGs that can be displayed on ZZ BNC. In this study, we introduced into BNC an Ig kappa light chain-binding B1 domain of Finegoldia magna protein L (protein-L B1 domain) and an Ig Fc-binding C2 domain of Streptococcus species protein G (protein-G C2 domain) to produce LG BNC. The LL-BNC was constructed in a similar way using a tandem form of the protein-L B1 domain. Both LG-BNC and LL-BNC could display rat IgGs, mouse IgG1, human IgG3, and human IgM, all of which not binding to ZZ-BNC, and accumulate in target cells in an antibody specificity-dependent manner. Thus, these BNCs could display a broad spectrum of Igs, significantly improving the prospects for BNCs as active targeting-based DDS nanocarriers. STATEMENT OF SIGNIFICANCE: We previously reported that ZZ-BNC, bio-nanocapsule deploying the IgG-binding Z domain of protein A, could display cell-specific antibody in an oriented immobilization manner, and act as an active targeting-based DDS nanocarrier. Since the Z domain can only bind to limited types of Igs, we generated BNCs deploying other Ig-binding domains: LL-BNC harboring the tandem form of Ig binding domain of protein L, and LG-BNC harboring the Ig binding domains of protein L and protein G sequentially. Both BNCs could display a broader spectrum of Igs than does the ZZ-BNC. When these BNCs displayed anti-CD11c IgG or anti EGFR IgG, both of which cannot bind to Z domain, they could bind to and then enter their respective target cells. PMID- 26876803 TI - The relationship between age and neurocognitive and daily functioning in adults with hoarding disorder. AB - OBJECTIVE: Given the increase in hoarding symptoms with age, there is a pressing need for understanding the clinical features as they relate to potential interventions for older adults with hoarding disorder (HD). The aim of the current investigation was to explore age-related differences in the level of functional and cognitive impairment in individuals with HD. METHODS: The current study utilized the baseline assessments of 122 adults with HD. Age-related differences in the raw scores of psychiatric, cognitive, and daily functioning were analyzed using a series of multiple regression models controlling for the possible age-related differences in premorbid IQ. RESULTS: Our results suggested that older adults with HD may experience increased levels of impairment in skills related to executive functioning and everyday functioning when compared with younger adults with HD. CONCLUSIONS: Given these difficulties with neurocognitive functioning, older HD patients may require interventions that focus more on behavioral and functional skills, rather than focusing on changing thought processes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26876804 TI - New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach. AB - The toxic effects of hexabromocyclododecane (HBCD) are complex, and the underlying toxicological mechanisms are still not completely understood. In this study, a pseudotargeted metabolomic approach based on the UHPLC/Q-Trap MS system was developed to assess the HBCD-intervention-related metabolic alteration in HepG2 cells. In addition, some physiologic indicators and relevant enzyme activities were measured. HBCD exposure obviously impaired metabolic homeostasis and induced oxidative stress, even at an environmentally relevant dose (0.05 mg/L). Metabolic profiling and multivariate analysis indicated that the main metabolic pathways perturbed by HBCD included amino acid metabolism, protein biosynthesis, fatty acid metabolism, and phospholipid metabolism. HBCD suppressed the cell uptake of amino acids, mainly through inhibition of the activity of membrane transport protein Na(+)/K(+)-ATPase. HBCD down-regulated glycolysis and beta-oxidation of long-chain fatty acids, causing a large decrease of ATP production. As a result, the across-membrane transport of amino acids was further inhibited. Meanwhile, HBCD induced a significant increase of total phospholipids, mainly through the remodeling of phospholipids from the increased free fatty acids. The obtained metabolomic results also provided some new evidence and clues regarding the toxicological mechanisms of HBCD that contribute to obesity, diabetes, nervous system damage, and developmental disorders. PMID- 26876806 TI - Reciprocal and unidirectional scattering of parity-time symmetric structures. AB - Parity-time (PT) symmetry is of great interest. The reciprocal and unidirectional features are intriguing besides the (PT) symmetry phase transition. Recently, the reciprocal transmission, unidirectional reflectionless and invisibility are intensively studied. Here, we show the reciprocal reflection/transmission in (PT) symmetric system is closely related to the type of (PT) symmetry, that is, the axial (reflection) (PT) symmetry leads to reciprocal reflection (transmission). The results are further elucidated by studying the scattering of rhombic ring form coupled resonators with enclosed synthetic magnetic flux. The nonreciprocal phase shift induced by the magnetic flux and gain/loss break the parity (P) and time-reversal (T) symmetry but keep the parity-time (PT) symmetry. The reciprocal reflection (transmission) and unidirectional transmission (reflection) are found in the axial (reflection) (PT)-symmetric ring centre. The explorations of symmetry and asymmetry from (PT) symmetry may shed light on novel one-way optical devices and application of (PT)-symmetric metamaterials. PMID- 26876805 TI - The Role of Physical Stabilization in Whole Blood Preservation. AB - The rapid degradation of blood ex vivo imposes logistical limitations on the utilization of blood-borne cells in medical diagnostics and scientific investigations. A fundamental but overlooked aspect in the storage of this fluid tissue is blood settling, which induces physical stress and compaction, aggregates blood cells, and causes collateral damage due to leukocyte activation. Here we show that the polymer Ficoll 70 kDa stabilized blood samples and prevented blood settling over the course of 72 hours, primarily by inhibiting depletion-mediated red blood cell aggregation. Physical stabilization decreased echinocyte formation, improved leukocyte viability, and inhibited the release of neutrophil elastase--a marker of neutrophil extracellular trap formation. In addition, Ficoll-stabilized blood was compatible with common leukocyte enrichment techniques including red blood cell lysis and immunomagnetic purification. This study showed for the first time that blood settling can be prevented using polymers and has implications in diagnostics. PMID- 26876807 TI - Time-dependent sorption of two novel fungicides in soils within a regulatory framework. AB - BACKGROUND: Convincing experimental evidence suggests increased sorption of pesticides on soil over time, which, so far, has not been considered in the regulatory assessment of leaching to groundwater. Recently, Beulke and van Beinum (2012) proposed a guidance on how to conduct, analyse and use time-dependent sorption studies in pesticide registration. The applicability of the recommended experimental set-up and fitting procedure was examined for two fungicides, penflufen and fluxapyroxad, in four soils during a 170 day incubation experiment. RESULTS: The apparent distribution coefficient increased by a factor of 2.5-4.5 for penflufen and by a factor of 2.5-2.8 for fluxapyroxad. The recommended two site, one-rate sorption model adequately described measurements of total mass and liquid phase concentration in the calcium chloride suspension and the calculated apparent distribution coefficient, passing all prescribed quality criteria for model fit and parameter reliability. CONCLUSION: The guidance is technically mature regarding the experimental set-up and parameterisation of the sorption model for the two moderately mobile and relatively persistent fungicides under investigation. These parameters can be used for transport modelling in soil, thereby recognising the existence of the experimentally observed, but in the regulatory leaching assessment of pesticides not yet routinely considered phenomenon of time-dependent sorption. (c) 2016 Society of Chemical Industry. PMID- 26876808 TI - Mesomeric configuration makes polyleucine micelle an optimal nanocarrier. AB - Micelle with mesomeric polyleucine (PDLLeu) core demonstrated the most uniform morphology, the smallest diameter and the highest drug loading capability compared to those with dextrorotatory (PDLeu), levorotatory (PLLeu) and racemic PLeu (PD/LLeu) cores. In addition, the modification with c(RGDfC) endowed the optimal PDLLeu micelle with enhanced intracellular drug release and cytotoxicity, indicating its great potential for targeted drug delivery. PMID- 26876812 TI - Plasma total C-terminal agrin fragment (tCAF) as a marker for kidney function in patients with chronic kidney disease. AB - BACKGROUND: Total C-terminal agrin fragment (tCAF) is a new biomarker that was previously correlated with kidney function. This article studies the validity of tCAF as a biomarker for kidney function in chronic kidney disease (CKD). METHODS: Plasma tCAF, serum creatinine (Cr), cystatin C (CyC), blood urea-nitrogen (BUN) concentrations and estimated glomerular filtration rate (eGFR CKD-EPIcrea cystatin) were assessed in 426 individuals [71 without CKD (CKD 0 degrees ) and 355 CKD patients]. In addition to descriptive statistics, univariate correlation between tCAF and biomarkers/eGFR was calculated; multiple linear regression modeling was applied between logarithmic (log) tCAF and log eGFR and adjusted for demographic data. The same methods were used to analyze the association of demographic factors and the different biomarkers adjusted for eGFR. RESULTS: Mean tCAF levels were 1012.2+/-789.9 pM. tCAF correlated with all biomarkers/eGFR in univariate analysis (eGFR: r=-0.77, Cr: r=0.74, BUN: r=0.66, CyC: r=0.75). Linear regression modeling revealed an excellent coefficient estimate between log tCAF and log eGFR (CKD-EPIcrea-cystatin) (-0.91, p<0.001). tCAF was the parameter least associated with demographic parameters in both univariate and multivariate regression modeling (only with age, coefficient estimate r=-0.159, p=0.001 in multivariate regression). CONCLUSIONS: In conclusion, tCAF is a promising biomarker for the assessment of kidney function in CKD patients showing an excellent correlation with eGFR and being less influenced by demographic parameters compared to conventional biomarkers. These preliminary results encourage further evaluation of tCAF in larger CKD cohorts and other clinical settings such as acute renal failure. PMID- 26876813 TI - What do we know about homocysteine and exercise? A review from the literature. AB - High total homocysteine (tHcy) concentrations contribute to an increased risk of cardiovascular diseases and neurodegenerative disorders. Several investigations have focused on the effect of exercise on tHcy concentrations, but results remain controversial. The differences among the methodologies in the investigations make difficult the interpretation of results. This review differentiates the effects of exercise on tHcy and establishes the relation with the implicated biomarkers on tHcy metabolism related to exercise. The electronic database MEDLINE (http://www.ncbi.nlm.nih.gov) was used for searching studies published between years 2002 and 2015. 'Homocysteine', 'Training ', 'Exercise', 'Physical Activity' as well as combinations out of these terms were entered in the database. Articles were grouped in: 1) Acute effect of exercise on tHcy, 2) chronic exercise and tHcy, 3) relationship of physical activity (PA) level and cardiorespiratory fitness with tHcy, and 4) biomarkers related to tHcy and exercise. From a total of 30 articles, most of the studies analyzing the acute effect of exercise showed an increase on tHcy concentrations. Studies analyzing the chronic effect on tHcy concentrations showed contradictory results and no consensus exists probably due to the differences in the methodology, exercise interventions and participants characteristics. Low cardiorespiratory fitness seems to be associated with high tHcy; in contrast, the relation of PA levels and tHcy needs further research. Regarding biomarkers related to tHcy and exercise, some studies showed an increase of folate, vitamin B12, and creatine after acute exercise that could to be due to requirement of protein turnover and an increased metabolic demand of vitamin-B. PMID- 26876814 TI - Aldosterone and type 2 diabetes mellitus. AB - Primary hyperaldosteronism (PA) has recently been demonstrated to be strictly associated to metabolic syndrome as compared with essential hypertension (EH). Besides, the characteristics of metabolic syndrome are different in PA compared to EH, as high fasting glucose is more frequent in the former condition. The adverse effect of excess aldosterone on insulin metabolic signaling has generated increasing interest in the role of hyperaldosteronism in the pathogenesis of insulin resistance and resistant hypertension. Moreover, aldosterone receptor antagonist therapy in diabetic and cardiopathic patients improved coronary flow. The aim of this review is to present recent knowledge about the relationship between aldosterone, insulin resistance and diabetes. PMID- 26876815 TI - 1,25-Dihydroxyvitamin D3 and type 2 diabetes: Ca2+-dependent molecular mechanisms and the role of vitamin D status. AB - The hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induces cellular Ca2+ signals which regulate insulin secretion, while low vitamin D status may be a risk factor for type 2 diabetes (T2D). In pancreatic beta-cells in vitro, 1,25(OH)2D3 induces, via multiple Ca2+ signaling pathways, synchronous Ca2+ oscillations, which quantitatively, temporally, and spatially pattern pulsatile insulin secretion from these cells. In animal studies employing a high fat diet-induced obesity model of pre-T2D, an increased intake of vitamin D delayed development of T2D and adiposity and was associated with the improved blood markers of diabetes and the vitamin D nutritional and hormonal status [plasma concentrations of glucose, insulin, adiponectin, 25-hydroxyvitamin D, and 1,25(OH)2D3]. Observational studies demonstrated associations between vitamin D status, insulin secretion and resistance to T2D, however, randomized controlled trials did not provide conclusive insights into the potential role of vitamin D in prevention of T2D. The 1,25(OH)2D3-dependent cellular Ca2+ signaling can be important for maintaining the normal level of insulin secretion from pancreatic beta-cells, and an increased intake of vitamin D may contribute to the prevention of T2D and metabolic disorders associated with this disease. PMID- 26876816 TI - Tuning the flexibility in MOFs by SBU functionalization. AB - A new approach for the fine tuning of flexibility in MOFs, involving functionalization of the secondary building unit, is presented. The "gate pressure" MOF [Zn3(bpydc)2(HCOO)2] was used as a model material and SBU functionalization was performed by using monocarboxylic acids such as acetic, benzoic or cinnamic acids instead of formic acid in the synthesis. The resulting materials are isomorphous to [Zn3(bpydc)2(HCOO)2] in the "as made" form, but show different structural dynamics during the guest removal. The activated materials have entirely different properties in the nitrogen physisorption experiments clearly showing the tunability of the gate pressure, at which the structural transformation occurs, by using monocarboxylic acids with varying backbone structure in the synthesis. Thus, increasing the number of carbon atoms in the backbone leads to the decreasing gate pressure required to initiate the structural transition. Moreover, in situ adsorption/PXRD data suggest differences in the mechanism of the structural transformations: from "gate opening" in the case of formic acid to "breathing" if benzoic acid is used. PMID- 26876817 TI - Preparation, optical and electrochemical properties, and molecular orbital calculations of tetraazaporphyrinato ruthenium (II) bis(4-methylpyridine) fused with one to four diphenylthiophene units. AB - 2,5-Diphenyl-3,4-dicyanothiophene (1) and phthalonitrile (2) were mixed and treated with ruthenium (III) trichloride, 4-methylpyridine, and 1,8 diazabicyclo[5.4.0]undec-7-ene (DBU) in 2-ethoxyethanol at 135 degrees C, to produce low-symmetrical tetraazaporphyrins (TAPs) (3), (4), (5), and (6) with one to three thiophene rings. Two thiophene-annelated tetraazaporphyrins were isolated as opposite and adjacent isomers 4 and 5. The structure of 3 was determined by X-ray crystallography, showing that the thiophene ring linked at the 3,4-positions on the tetraazaporphyrin scaffold deviates from the mean plane of the four central pyrrole nitrogen atoms (N1-N3-N5-N7). Optical and electrochemical properties of the products were examined by UV-vis and magnetic circular dichroism (MCD) spectroscopy, together with cyclic voltammetry. In the (1)H NMR spectra, the signals of 4-methylpyridine coordinating to the central ruthenium atom appeared at a higher magnetic field than those of uncoordinated 4 methylpyridine itself due to the shielding effect of the TAP ring. Increasing the number of fused thiophene rings resulted in 1) lower magnetic field shifts of the signals of axially coordinated 4-methylpyridine in the (1)H NMR spectra, 2) lower energy shifts of the Q band absorption in the UV-vis spectra, and 3) decreasing (cathodic shift) of the first oxidation potentials. The structures of simplified model compounds were optimized using the DFT method with the Gaussian 09 program at the B3LYP/LANL2DZ level for the Ru atom and the B3LYP/6-31G (d, p) level for the C, H, N, and S atoms. The optimized structures were utilized to calculate the NMR shielding constants, the HOMO and LUMO orbital energies, and the electronic absorption spectra. PMID- 26876818 TI - Impact of preoperative embolization on the outcomes of carotid body tumor surgery: A meta-analysis and review of the literature. AB - BACKGROUND: There is no consensus on the impact of preoperative embolization (EMB) on the surgical outcomes of carotid body tumor (CBT) resections. METHODS: A systematic review and a meta-analysis were conducted to clarify the role of preoperative EMB in patients undergoing surgical removal of CBTs. RESULTS: Fifteen studies with a total number of 470 patients met the inclusion criteria. The results of the meta-analysis showed that there is no significant difference in estimated blood loss, operative time, length of hospital stay, or risks of cranial nerve injury, vascular injury, and stroke between the EMB and nonembolization (NEMB) groups. CONCLUSION: This systemic review and meta-analysis demonstrate that preoperative EMB does not confer any operative or postoperative advantage in patients scheduled for CBT surgery. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2386-E2394, 2016. PMID- 26876819 TI - Genetic Variation in the Vesicular Monoamine Transporter 1 (VMAT1/SLC18A1) Gene and Alcohol Withdrawal Severity. AB - BACKGROUND: Alcohol withdrawal (AW) can be a serious consequence of alcohol dependence and consists of various neurochemical adaptations in the brain. One such neuroadaptation occurs in the monoamine neurotransmitter system. Recently, a functional variant in the presynaptic vesicular monoamine transporter gene (VMAT1/SLC18A1-Thr136Ile-rs1390938) was found to significantly increase transport of monoamines into synaptic vesicles in vitro. We hypothesize that the alteration of magnitude of monoamine release contributes to severity of AW symptoms. METHODS: Alcohol-dependent individuals (n = 609; European American n = 340; African American n = 216; other n = 53) were administered the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) questionnaire at the time of inpatient admission. Patients were subsequently genotyped for 12 single nucleotide polymorphism (SNP) markers in VMAT1. Association analyses were conducted on the combined sample and separated by ethnicity. RESULTS: Single marker association tests revealed a significant association between 3 VMAT1 markers and CIWA-Ar scores in the EA sample. The minor alleles of rs1390938 (A) and rs952859 (C) were significantly associated with lower CIWA-Ar scores (p = 0.0006; p = 0.0007), whereas the minor allele of rs3779672 (G) was significantly associated with higher scores (p = 0.006). Additionally, these 3 SNPs were found in a haplotype block that was significantly associated with lower CIWA-Ar scores after haplotype analyses were run (p = 0.009). CONCLUSIONS: This study shows that genetic variants in VMAT1, including the functional SNP rs1390938, contribute to the severity of AW in patients of European descent. Our data show for the first time a role of presynaptic neurotransmitter release in AW severity. This finding could contribute to identifying patients at risk for severe AW and shed light into the pathophysiology of AW and its treatment. PMID- 26876820 TI - Recognizing a limitation of the TBLC-activated peroxide system on low-temperature cotton bleaching. AB - In this study, cotton was bleached at low temperatures with an activated peroxide system which was established by incorporating a bleach activator, namely, N-[4 (triethylammoniomethyl)benzoyl]caprolactam chloride (TBCC) into an aqueous solution of hydrogen peroxide (H2O2). Experimental results showed that the bleaching performance was unexpectedly diminished as the TBCC concentration was increased over the range of 25-100g/L. Kinetic adsorption experiment indicated that this was most likely ascribed to the adsorptive interactions of TBCC and the in situ-generated compounds with cotton fibers. Such a limitation was especially fatal to cold pad-batch bleaching process of cotton in which a high TBCC concentration was often required. The results of this study may stimulate further research to avoid or overcome the limitation of the TBCC-activated peroxide system on low-temperature cotton bleaching. PMID- 26876821 TI - Structural analysis and immunoregulation activity comparison of five polysaccharides from Angelica sinensis. AB - Four fractional polysaccharides (CAPS30, CAPS50, CAPS70 and CAPS80) and total polysaccharides (CAPSt) were obtained from Angelica sinensis. Their structures were identified by Fourier transform-infrared spectroscopy (FT-IR), molecular weights were evaluated by high performance gel permeation chromatography (HPGPC) and compositions were analyzed by gas chromatography-mass spectrometry (GC-MS). Their immunoregulation activities were further compared in vitro. The results showed that they displayed different structural features and immuno-enhancement activities. They all could cause the proliferation of the lymphocyte, up-regulate stimulate the productions of IFN-gamma, IL-2, IL-6 and TNF-alpha secretion in the peripheral lymphocytes. Further experiments showed that CAPS50 and CAPS70 could increase the ratio of CD3(+)CD56(+) cells to some extent. These indicated that five CAPSs displayed different activities which were associated with their different structural characteristics and CAPS70, with the molecular weights of 20.82kDa and consisting of mannose and glucose in the molar ratio of 1.20:1.01, possessed the strongest immuno-enhancement activity. PMID- 26876822 TI - Photochemical depolymerisation of dermatan sulfate and analysis of the generated oligosaccharides. AB - Radical depolymerisation is the method of choice for the depolymerisation of glycosaminoglycans (GAGs), especially when enzymatic depolymerisation cannot be performed due to the lack of suitable enzymes. The established Fenton type free radical depolymerisation generates radicals from a solution of H2O2 in the presence of Cu(2+) or Fe(2+). When applied to dermatan sulfate (DS), the Fenton type depolymerisation of DS (Panagos, Thomson, Bavington, & Uhrin, 2012) produced exclusively oligosaccharides with reducing end GalNAc, which was partially oxidised to acetylgalactosaminic acid. We report here the results of the TiO2 catalysed photochemical depolymerisation of DS. NMR analysis of these DS oligosaccharides revealed the presence of reducing end IdoA, observed for the first time. The reducing end acetylgalactosaminic acid was also detected. The photochemical depolymerisation method thus enables preparation of new types of GAG oligosaccharides suitable for further biochemical and biological investigation. PMID- 26876823 TI - Microencapsulation of saffron petal anthocyanins with cress seed gum compared with Arabic gum through freeze drying. AB - In this research, encapsulation efficiency of cress seed gum (CSG) as a native hydrocolloid was compared with Arabic gum (AG) and maltodextrin (dextrose equivalent of 20 (M20), and 7 (M7)) for saffron (Crocus sativus) petal's extract by freeze drying method. Combinations of CSG-M20, AG-M20, and M7-M20 with ratios of 50:50 and M20 alone (100%) were used as wall materials. A mixture of 1:5 (based on dry matter) between core (concentrated anthocyanin extract of saffron petal) and wall materials were freeze dried and stability of encapsulated anthocyanins along with color parameters (a*, b*, L*, C, H degrees and TCD) of final powders were measured during 10 weeks of storage (at 35 degrees C as an accelerated method). Total anthocyanins were determined through pH differential method every week. Four prepared formulations of encapsulated powders didn't show any significant differences (P>0.01) in terms of total anthocyanin content measured immediately after production and after 10 weeks storage. AG-M20 mixture and M20 alone showed the highest and lowest TCD, respectively. The mixture of CSG M20 in comparison with AG-M20 and M20 had the same protecting effect (P<0.01) but showed a relatively high TCD (9.33). PMID- 26876824 TI - Study of intragastric structuring ability of sodium alginate based o/w emulsions under in vitro physiological pre-absorptive digestion conditions. AB - In the present work, the intragastric structuring ability of o/w emulsions either stabilised (1-4%, w/w of sodium alginate (SA)) or structured with sheared ionic gel (1-3%, w/w of SA crosslinked with Ca(2+)) in the absence (saliva and gastric phases constituted of deionised water) or presence of in vitro pre-absorptive conditions (physiological simulated saliva and gastric fluids) was investigated. Visualisation of the morphological aspects of the gastric chymes, in the absence of multivalent counterions, demonstrated that SA stabilised systems underwent a remarkable swelling in the pH range of 2-3, whilst at the same pH range, ionic SA gel structured systems maintained their major structure configuration. When the aforementioned systems were exposed to physiological intragastric fluids, a reduction of the length and the hydrodynamic volume of the alginate fibres was detected regardless the structuring approach. On their exposure to physiological intragastric conditions (pH=2), SA stabilised emulsions underwent sol-gel transition achieving a ca. 3- to 4-order increase of storage modulus (at 1Hz). In the case of ionic sheared gel structured emulsions, exposure to physiological intragastric fluids resulted in a 10-fold reduction ability of their acid structuring ability, most likely due to the dialysis of egg-box dimer conformations by monovalent cations and protons and the sterical hindering of hydrogen bonding of MM and GG sequences under acidic conditions. Using of non physiological simulated intragastric fluids was associated with overestimated structuring performance of SA regardless its physical state. PMID- 26876825 TI - Reversible redox activity of ferrocene functionalized hydroxypropyl cellulose and its application to detect H2O2. AB - Novel ferrocene functionalized hydroxypropyl cellulose (HPC-Fc) were prepared by azide-alkyne cycloaddition and characterized. HPC-Fc exhibits an excellent reversible redox activity and could establish amazing electron transfer ability between enzyme and electrode. HPC-Fc and horseradish peroxidase (HRP) were coated on a platinized carbon electrode to prepare an amperometric biosensor for hydrogen peroxide (H2O2) detection. The amperometric response was measured as a function of H2O2 concentration at a fixed potential of 0.35V in 100mM phosphate buffer solution (pH 7.0). The novel biosensor exhibits a fast linear response toward H2O2 in the range of 0.1-8MUM with sensitivity of 4.21nA/MUM. Moreover, the enzyme assays measured by the spectrophotometer method confirm that abundant hydroxyl groups of HPC backbones are conductive for HRP to maintaining or even enhancing their activity. The redox active HPC-Fc with the unique properties of both ferrocene and cellulose is a good candidate for biosensor applications. PMID- 26876826 TI - Flexible conductive nanocellulose combined with silicon nanoparticles and polyaniline. AB - Here we describe a unique conductive bacterial cellulose (BC) composite with silicon nanoparticles (SiNPs) and polyaniline. BC was used as a template for binding SiNPs resulting in a very promising anode material for Li-ion rechargeable batteries that showed a high specific capacity. The surfaces of the SiNPs were modified with phytic acid to enhance the binding of aniline monomer to the surface. A conformal coating of polyaniline (PANi) was formed on the modified SiNPs by in situ polymerization of aniline monomers. We also found that the phytic acid on the SiNPs was critical to ensure encapsulation of SiNPs with PANi. In addition, the phosphoric acid-tagged surface of the SiNPs enhanced the adhesion of SiNPs to the BC fibers. The resulting three dimensional network of BC was flexible and provided stress dissipation in the conductive BC composites. Flexural testing of conductive BC composites showed stable electrical conductivity even after repetitive bending over 100 times. PMID- 26876827 TI - Rapid enrichment of rare-earth metals by carboxymethyl cellulose-based open cellular hydrogel adsorbent from HIPEs template. AB - A series of monolithic open-cellular hydrogel adsorbents based on carboxymethylcellulose (CMC) were prepared through high internal phase emulsions (HIPEs) and used to enrich the rare-earth metals La(3+) and Ce(3+). The changes of pore structure, and the effects of pH, contact time, initial concentration on the adsorption performance were systematically studied. The results show that the as-prepared monolithic hydrogel adsorbents possess good open-cellular framework structure and have fast adsorption kinetics and high adsorption capacity for La(3+) and Ce(3+). The involved adsorption system can reach equilibrium within 30min and the maximal adsorption capacity is determined to be 384.62mg/g for La(3+) and 333.33mg/g for Ce(3+). Moreover, these porous hydrogel adsorbents show an excellent adsorptive reusability for La(3+) and Ce(3+) through five adsorption desorption cycles. Such a pore hierarchy structure makes this monolithic open cellular hydrogel adsorbent be an effective adsorbent for effective enrichment of La(3+) and Ce(3+) from aqueous solution. PMID- 26876828 TI - Optimization of microwave assisted extraction of pectin from sour orange peel and its physicochemical properties. AB - Microwave assisted extraction technique was used to extract pectin from sour orange peel. Box-Behnken design was used to study the effect of irradiation time, microwave power and pH on the yield and degree of esterification (DE) of pectin. The results showed that the optimum conditions for the highest yield of pectin (29.1%) were obtained at pH of 1.50, microwave power of 700W, and irradiation time of 3min. DE values of pectin ranged from 1.7% to 37.5%, indicating that the obtained pectin was low in methoxyl. Under optimal conditions, the galacturonic acid content and emulsifying activity were 71.0+/-0.8% and 40.7%, respectively. In addition, the emulsion stability value ranged from 72.1% to 83.4%. Viscosity measurement revealed that the solutions of pectin at low concentrations showed nearly Newtonian flow behavior, and as the concentration increased, pseudoplastic flow became dominant. PMID- 26876829 TI - Facile and green synthesis of cellulose nanocrystal-supported gold nanoparticles with superior catalytic activity. AB - The emphasis of science and technology shifts toward environmentally friendly and sustainable resources and processes. Herein, we report a facile, one-pot and green synthesis of biomaterial-supported gold nanoparticles (AuNPs) with superior catalytic activity. Cellulose nanocrystal (CNC)-supported AuNPs were prepared by heating the aqueous mixture of HAuCl4, CNCs and polyethylene glycol, avoiding toxic chemicals, extreme condition and complicated procedure. The resultant CNC supported AuNPs exhibited catalytic activities for the reduction of 4-nitrophenol by sodium borohydride. The maximum apparent rate constant reached 1.47*10(-2)s( 1), and the turnover frequency reached 641h(-1). The superior catalytic performance can be ascribed to the large amount of highly dispersed AuNPs with few nanometers in size which are loaded on CNCs. About 90% of the AuNPs are smaller than 10nm, and nearly 60% of the AuNPs are smaller than 5nm. The synthesis is eco-friendly, facile and low-cost, thus has great potential for industrial and medical applications. PMID- 26876830 TI - Hydrogels made from chitosan and silver nitrate. AB - This work describes a gelation of chitosan solution with silver nitrate. Above the critical concentration of chitosan (c*), continuous hydrogels of chitosan silver can be formed. At lower concentrations, the formation of nano- and micro hydrogels is discussed. The sol-gel analysis was performed to characterise the hydrogels' swelling properties. Moreover, the following were employed: (i) mechanical testing of hydrogels, (ii) inductively coupled plasma-optical emission spectroscopy (ICP-OES) for the measurement of silver concentration, (iii) scanning electron microscopy (SEM) to examine the morphology of products obtained, and (iv) dynamic light scattering (DLS) and UV-vis spectrophotometry to examine products formed at low concentration of chitosan (c=4 or >=7)/anxiety (Hospital Anxiety and Depression Scale-Anxiety >=8)/depression (Hospital Anxiety and Depression Scale-Depression >=8) and demographic factors. RESULTS: A total of 125 participants completed the study (78% response rate). ECA was associated with depression (p <0.001), anxiety (p = 0.001), and distress (p = 0.006), meeting cut-off threshold criteria for distress (p = 0.024), anxiety (p = 0.048), and depression (p = 0.001). On multivariate analysis, only depression (p = 0.04) and emotional issues (i.e., component of Distress Thermometer and Problem List) (p = 0.001) were associated with ECA. Neglect, but not Abuse and Chaotic Home Environment, was associated with depression (beta = 0.442, p < 0.001), anxiety (beta = 0.342, p = 0.002), and self identified problems with family (beta = 0.288, p = 0.022), emotion (beta = 0.345, p = 0.004), and physical issues (beta = 0.408, p < 0.001). CONCLUSION: ECA and neglect are associated with multiple psychologic symptoms, but most specifically depression in the setting of breast cancer. ECA contributes to psychologic burden as a vulnerability factor. ECA may help to explain individual patient trajectories and influence the provision of patient-centered care for psychologic symptoms in patients with breast cancer. PMID- 26876890 TI - Expression and Purification of Recombinant Mouse Interleukin-4 and -6 from Transgenic Rice Seeds. AB - Transgenic rice seed can be utilized as a bioreactor to produce high-value recombinant proteins. Mouse interleukin 4 (mIL-4) and mIL-6 were specifically expressed as secretory proteins in rice endosperm by ligating the N-terminal glutelin B-1 (GluB-1) signal peptide and the C-terminal KDEL endoplasmic reticulum retention signal under control of the endosperm-specific GluB-1 promoter. In the transgenic rice seed, mIL-4 and mIL-6 accumulated in levels up to 0.43 mg/g grain and 0.16 mg/g grain, respectively. The reducing agents and detergents required for extraction from the transgenic rice seeds differed between the two proteins, indicating differences in their intracellular localization within the endosperm cell. Purified mIL-4 and mIL-6 exhibited high activity and very low endotoxin contamination. PMID- 26876891 TI - Comparative speed of kill of sarolaner (Simparica) and afoxolaner (NexGard against induced infestations of Ixodes scapularis on dogs. AB - BACKGROUND: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs and cats in North America and is the main vector for the pathogen that causes Lyme disease in dogs and humans. The speed of kill of a parasiticide is critical to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of tick-borne pathogen transmission. In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica), against I. scapularis on dogs was evaluated and compared with afoxolaner (NexGard) for five weeks after a single oral dose. METHODS: Twenty four dogs were randomly allocated to treatment with either placebo, sarolaner (2 to 4 mg/kg), or afoxolaner (2.5 to 6.8 mg/kg) based on pretreatment tick counts. Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs. RESULTS: A single oral dose of sarolaner provided >99% efficacy within 24 h of treatment and >95% against subsequent weekly re-infestations of ticks consistently to Day 35. For the earlier time points, sarolaner significantly reduced tick counts versus placebo from Day 0 to Day 21 at 8 and 12 h, and on Day 35 at 12 h (P <= 0.0174), while afoxolaner was only significantly lower at 8 h on Days 0 and 14 (P <= 0.0309), and at 12 h on Day 0 only (P < 0.0001). Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 14 to Day 35 (P <= 0.0278). At 24 h, efficacy (based on geometric mean counts) of afoxolaner declined to less than 80% from Day 21 through the end of the study, while efficacy for sarolaner was >95% for 35 days. There were no adverse reactions to treatments. CONCLUSIONS: In this controlled laboratory evaluation, sarolaner had a faster speed of kill against I. scapularis than afoxolaner. This was noticeably more pronounced towards the end of the monthly treatment period. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and re-infestation over 35 days suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and should reduce the risk of tick-borne diseases, including Lyme disease whose agent is vectored by I. scapularis. PMID- 26876892 TI - Cavernous hemangioma of the internal auditory canal encasing the VII and VIII cranial nerve complex: case report and review of the literature. AB - Cavernous angiomas originating in the internal auditory canal are very rare. In the available literature, only 65 cases of cavernomas in this location have been previously reported. We describe the case of a 22-year-old woman surgically treated for a cavernous hemangioma in the left internal auditory canal, mimicking on preoperative magnetic resonance imaging MRI an acoustic neuroma. Neurological symptoms were hypoacusia and dizziness. The cavernous angioma encased the seventh and, partially, the eighth cranial nerve complex. A "nearly total" removal was performed, leaving a thin residual of malformation adherent to the facial nerve. Postoperative period was uneventful; hearing was unchanged, but the patient had a moderate inferior left facial palsy (House-Brackmann grade II) slightly improved during the following weeks. On the basis of the observation of this uncommon case, we propose a revision of the literature and discuss clinical features, differential diagnosis, and treatment. PMID- 26876889 TI - Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams. AB - Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited. Designing methods for streaming data capture, real-time data aggregation, machine learning, predictive analytics and visualization solutions to integrate wellness or health monitoring data elements with the electronic medical records (EMRs) maintained by health care providers permits better utilization. Integration of population-scale biomedical, health care and wellness data would help to stratify patients for active health management and to understand clinically asymptomatic patients and underlying illness trajectories. In this article, we discuss various health-monitoring devices, their ability to capture the unique state of health represented in a patient and their application in individualized diagnostics, prognosis, clinical or wellness intervention. We also discuss examples of translational bioinformatics approaches to integrating patient-generated data with existing EMRs, personal health records, patient portals and clinical data repositories. Briefly, translational bioinformatics methods, tools and resources are at the center of these advances in implementing real-time biomedical and health care analytics in the clinical setting. Furthermore, these advances are poised to play a significant role in clinical decision-making and implementation of data-driven medicine and wellness care. PMID- 26876893 TI - Management of symptomatic hemifacial spasm or trigeminal neuralgia. AB - Hemifacial spasm (HFS) or trigeminal neuralgia (TN) is a kind of hyperactivity disorder of cranial nerves caused by vascular compression. However, sometimes, the disease may arise from nerve damage produced by tumors, which was called as symptomatic HFS/TN. Until now, little is known about the exact mechanism and the necessity of microvascular decompression (MVD) regarding the tumor-induced HFS/TN, which is necessary to be retrospectively analyzed in a considerable sample. Among the 4021 patients who underwent MVD in our department between 2006 and 2014, 44 were finally diagnosed as symptomatic HFS or TN. These patients were focused in this study and their clinical features as well as intraoperative findings and postoperative outcomes were retrospectively investigated. Data analysis exhibited the symptomatic HFS/TN cases accounted for 1.1 % in the study, which were caused by epidermoid in 18 (40.9 %) and meningioma in 15 (34.1 %) followed by neuroma in 7 (15.9 %) as well as aneurysm in 2 (4.5 %) and arteriovenous malformation in 2 (4.5 %). Compared to those with idiopathic HFS/TN, younger females were more susceptible (p < 0.05). After resection of the neoplasm, the offending vessel was identified in 26 (59.1 %), which were followed by MVD process. Postoperatively, the symptoms relief rate was 88.6 %. Our study showed that surgical management of patients with symptomatic HFS/TN may lead to a satisfactory result, yet those primary lesions should be removed firstly. In some cases, a microvascular decompression process might be unnecessary afterward, but the entire nerve root should be checked to exclude any vessel in contact with. PMID- 26876894 TI - Cultural immersion through international experiences among Japanese nurses: Present status, future intentions, and perceived barriers. AB - AIM: Given limited exposure to various ethnicities, languages, and cultures, providing health care to an increasing foreign population in Japan will likely be challenging for Japanese nurses. This study aimed to examine past and intended future international experiences of Japanese nurses to assess their cultural immersion level. METHODS: A cross-sectional electronic survey was conducted among 2029 nurses in 2010. Participants were categorized by travel purpose, and the frequency of non-holiday travel was analyzed. To examine participants' desire for and perceived feasibility of future non-holiday international experiences by background characteristics, logistic regression analyses were performed. RESULTS: Of 1039 participants, 10.1% had past non-holiday international experiences, with 80% having traveled to high-income, English-speaking countries. The median value for travel frequency was once, and the median duration of travel was less than 1 month. The most common purpose of travel was participation in short-term programs (e.g. professional training, language study). Fifty-one percent of female nurses reported a desire for future non-holiday international experiences. Of these, 37.2% considered such experiences feasible. Age of the youngest child, having nursing specialization, English proficiency, and past international experience were significant predictors for feasibility. CONCLUSION: Japanese nurses with foreign experience were considered valuable human resources for culturally appropriate care. Efforts should be made to integrate them into the Japanese healthcare setting. The present study revealed room for improvement in foreign language proficiency and cross-cultural training with a focus on non-English speaking and developing countries. A supportive workplace environment should be created that allows nurses to pursue the international experiences they desire. PMID- 26876896 TI - Success rates for product development strategies in new drug development. AB - WHAT IS KNOWN AND OBJECTIVE: While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. METHODS: We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. RESULTS AND DISCUSSION: Combined experience strategies had the highest success rate. More than three and a half percent (0.036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0.025) with novel strategies trailing closely (0.024). Indication experience strategies are the least successful (0.008). These differences are statistically significant. WHAT IS NEW AND CONCLUSION: The primary contribution of this study is that product development strategies combining experience with drugs and indications strategies are the most likely to reach the market, even though they are least common strategy. Therefore, combined experience strategies remain underutilized. The findings also suggest a promising path for pursuing combined experience strategies: gaining expertise with drugs is likely to be a more effective path to gaining the expertise necessary for developing subsequent recombination strategies. PMID- 26876897 TI - Where we are with screening and risk prediction for prostate cancer in 2016. PMID- 26876895 TI - Ultrasound-guided plasma rich in growth factors injections and scaffolds hasten motor nerve functional recovery in an ovine model of nerve crush injury. AB - In the present study we evaluated the motor recovery process of peripheral nerve injury (PNI), based on electrophysiological and histomorphometric criteria, after treatment with plasma rich in growth factors (PRGF) injections and scaffolds in an ovine model. Three groups of sheep underwent a nerve crush lesion: the first group (n = 3) was left to recover spontaneously (SR); the second group was administered saline injections (SI; n = 5) and a third group (n = 6) received PRGF injections and scaffolds immediately after the crush injury. At post intervention week 8, 70% of sheep in the PRGF group were CMAP-positive, with no electrophysiological response in the rest of the groups. Histomorphometric analysis 12 weeks after the surgical intervention revealed that the average axonal density of the SR (1184 +/- 864 axons/um2 ) and SI (3109 +/- 2450 axons/um2 ) groups was significantly inferior to the control (8427 +/- 2433 axons/um2 ) and also inferior to the PRGF group (5276 +/- 4148 axons/um2 ), showing no significant differences between the control and PRGF groups. The axonal size of the SR and SI groups was significantly smaller compared with the control group (18 +/- 4 um2 ), whereas the axonal size of the PRGF group (6 +/- 5 um2 ) did not show statistical differences from the control. Morphometry of the target muscles indicated that the PRGF group had the lowest percentage volume reduction 12 weeks after the crush injury. The PRGF group had larger muscle fibre areas than the SI and SR groups, although the differences did not reach statistical significance. Overall, these data suggest that the PRGF injections and scaffolds hastened functional axon recovery and dampened atrophy of the target muscles in an ovine model. Copyright (c) 2015 John Wiley & Sons, Ltd. PMID- 26876898 TI - Prostate cancer risk prediction and the persistence of uncertainty. PMID- 26876899 TI - TRPM8 antagonists to treat lower urinary tract symptoms: don't lose your cool just yet. PMID- 26876900 TI - New evidence from the Prostate Cancer Prevention Trial may exculpate cyclooxygenase (COX) blockers in erectile dysfunction. PMID- 26876901 TI - Design of defect spins in piezoelectric aluminum nitride for solid-state hybrid quantum technologies. AB - Spin defects in wide-band gap semiconductors are promising systems for the realization of quantum bits, or qubits, in solid-state environments. To date, defect qubits have only been realized in materials with strong covalent bonds. Here, we introduce a strain-driven scheme to rationally design defect spins in functional ionic crystals, which may operate as potential qubits. In particular, using a combination of state-of-the-art ab-initio calculations based on hybrid density functional and many-body perturbation theory, we predicted that the negatively charged nitrogen vacancy center in piezoelectric aluminum nitride exhibits spin-triplet ground states under realistic uni- and bi-axial strain conditions; such states may be harnessed for the realization of qubits. The strain-driven strategy adopted here can be readily extended to a wide range of point defects in other wide-band gap semiconductors, paving the way to controlling the spin properties of defects in ionic systems for potential spintronic technologies. PMID- 26876902 TI - Recent Progress in Cell Reprogramming Technology for Cell Transplantation Therapy. AB - The discovery of induced pluripotent stem (iPS) cells opened the gate for reprogramming technology with which we can change the cell fate through overexpression of master transcriptional factors. Now we can prepare various kinds of neuronal cells directly induced from somatic cells. It has been reported that overexpression of a neuron-specific transcriptional factors might change the cell fate of endogenous astroglia to neuronal cells in vivo. In addition, some research groups demonstrated that chemical compound can induce chemical-induced neuronal cells, without transcriptional factors overexpression. In this review, we briefly review recent progress in the induced neuronal (iN) cells, and discuss the possibility of application for cell transplantation therapy. PMID- 26876903 TI - Hearing Preservation after Low-dose Gamma Knife Radiosurgery of Vestibular Schwannomas. AB - The objective of the retrospective study was to evaluate the factors associated with hearing preservation after low-dose Gamma Knife radiosurgery (GKS) of vestibular schwannomas performed according to the modern standards. From January 2005 to September 2010, 141 consecutive patients underwent such treatment in Tokyo Women's Medical University. Mean marginal dose was 11.9 Gy (range, 11-12 Gy). The doses for the brain stem, cranial nerves (V, VII, and VIII), and cochlea were kept below 14 Gy, 12 Gy, and 4 Gy, respectively. Out of the total cohort, 102 cases with at least 24 months follow-up were analyzed. Within the median follow-up of 56 months (range, 24-99 months) the crude tumor growth control was 92% (94 cases), whereas its actuarial rate at 5 years was 93%. Out of 49 patients with serviceable hearing on the side of the tumor before GKS, 28 (57%) demonstrated its preservation at the time of the last follow-up. No one evaluated factor, namely Gardner-Robertson hearing class before irradiation, Koos tumor stage, extension of the intrameatal part of the neoplasm up to fundus, nerve of tumor origin, presence of cystic changes in the neoplasm, and cochlea dose demonstrated statistically significant association with preservation of the serviceable hearing after radiosurgery. In conclusion, GKS of vestibular schwannomas performed according to the modern standards of treatment permits to preserve serviceable hearing on the side of the tumor in more than half of the patients. The actual causes of hearing deterioration after radiosurgery remain unclear. PMID- 26876904 TI - Origin of polyproline-rich peptides in human butyrylcholinesterase tetramers. AB - The human butyrylcholinesterase (HuBChE) tetramer is composed of 4 identical subunits and a noncovalently bound polyproline-rich peptide. In a previous report we identified lamellipodin as the source of the polyproline-rich peptides in HuBChE tetramers purified from plasma. Our current goal was to identify proteins in addition to lamellipodin that donate polyproline-rich peptides to plasma HuBChE tetramers. Peptides were released from 1 mg of pure plasma-derived HuBChE tetramers by boiling. Mass spectrometry identified 74 polyproline-rich peptides. MALDI-TOF mass spectra and spectral counting of the LC-MS/MS data supported the conclusion that lamellipodin accounted for 70% of the polyproline-rich peptides. Additional precursor proteins were matched through BLASTp searches, suggesting but not proving, that 20 proteins including UDP-N-acetyl glucosamine transferase ALG13 homolog, leiomodin 2, and zinc finger homeobox protein 2 are sources of polyproline-rich peptides found in HuBChE tetramers. Eighteen polyproline-rich peptides had no match in the human protein database. In conclusion, HuBChE assembles into tetramers through interaction of its C-terminal domain with polyproline peptides derived from a variety of proteins. PMID- 26876905 TI - Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity. AB - The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-kappaB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy. PMID- 26876906 TI - Eating disorder pathology in elite adolescent athletes. AB - OBJECTIVE: We aimed to investigate eating disorder pathology in German elite adolescent athletes. Evidence suggests that eating disorder pathology is more common in adult elite sports, especially in female athletes and in sports emphasizing leanness. There is a scarcity of studies in elite adolescent athletes who are in a vulnerable developmental stage and are affected by general as well as sport-specific risk factors. METHOD: Our data was derived from the German Young Olympic Athletes' Lifestyle and Health Management Study (GOAL) which conducted a survey in 1138 elite adolescent athletes. In this sample, we assessed body weight, weight control behavior, body acceptance and screened overall for core symptoms of eating disorders, depression and anxiety. We performed a tree analysis to identify high risk groups for eating disorder pathology. RESULTS: High risk groups comprised (a) athletes competing in weight dependent sports, and among athletes competing in disciplines other than weight dependent sports (b) athletes who are high on negative affectivity, (c) female athletes and (d) male athletes competing in endurance, technical or power sports. Athletes competing in weight dependent disciplines reported wide spread use of compensatory behaviors to influence body weight. Athletes reporting eating disorder pathology showed higher levels of depression and anxiety than athletes without eating disorder pathology. DISCUSSION: Increased psychosocial burden in athletes with eating disorder pathology suggests that eating disorder symptoms should not be accepted as an unproblematic and functional part of elite sports. The prevention and management of eating disorder pathology is especially important in weight dependent sports. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:553 562). PMID- 26876907 TI - Hybrid framework with cobalt-chromium alloy and gold cylinder for implant superstructure: Bond strength and corrosion resistance. AB - PURPOSE: The aim of this in vitro study was to evaluate tensile bond strengths and corrosion resistance of CoCr alloys joined with gold cylinder by a soldering system in comparison with the conventional cast-joining system. METHODS: CoCr alloys joined with gold cylinder by a soldering system using a high-fusing gold solder (CoCr/Solder/Gold cylinder), gold alloy joined with gold cylinder by a cast joining system (Gold alloy/Gold cylinder) and CoCr castings were fabricated. The tensile bond strength and corrosion resistance in 0.9% NaCl solution (pH 7.4 and pH 2.3) were evaluated. Scanning electron microscopy (SEM) of the fractured surface and electron probe microanalysis (EPMA) of the joined interfaces were also performed. RESULTS: The tensile bond strengths of the CoCr/Solder/Gold cylinder specimens showed similar values as the Gold alloy/Gold cylinder specimens. SEM observation and EPMA analyses suggested firm bonding between the CoCr alloy and gold cylinder. The released elements from the CoCr/Solder/Gold cylinder specimens were similar to ones from CoCr castings. CONCLUSIONS: Results showed that superstructures made of CoCr alloys joined with the gold cylinder using a high-fusing gold solder had sufficient bond strength and high corrosion resistance. These hybrid frameworks with cobalt-chromium alloy and gold cylinder are promising prosthesis for implant superstructures with the low cost and favorable mechanical properties instead of conventional high-gold alloys. PMID- 26876908 TI - Diagnostic validity of self-reported measures of sleep bruxism using an ambulatory single-channel EMG device. AB - PURPOSE: Self-reported measures have been widely used to indicate the presence of possible and probable sleep bruxism (SB) in both research and clinical situations. However, few studies have attempted to assess the diagnostic validity of this approach. The aim of this study was to estimate the diagnostic validity of self-reported measures of SB using an ambulatory single-channel electromyographic (EMG) device. METHODS: A total of 115 participants were enrolled and examined by standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) including two questions related to SB: self reported SB and morning-jaw symptoms. An ambulatory single-channel EMG device (GrindCare3TM, Medotech A/S) was used for measuring jaw-muscle EMG activity during sleep for seven consecutive nights. Cut-off values for different measures of EMG activity (average, maximum and minimum) and the coefficient of variation (CV) were selected to divide participants into two groups, with higher or lower EMG activity or CV values. The sensitivity and specificity for each question and combination of them were calculated. RESULTS: Self-reported SB had the highest sensitivity (compared with morning-jaw symptoms) for all measures of EMG activity and CV, although the values were low to modest (average: 76.0%, maximum: 76.9%, minimum: 77.3%, CV: 61.0%). The specificity was low for both the questions related to the different measures of EMG activity and CV (35.1-52.4%). CONCLUSIONS: This study indicated that the diagnostic validity of self-reported measures of SB was low to modest using an ambulatory EMG device assessment as a reference. Using only self-reported measures for the assessment of SB may not have a high validity, which should be taken into consideration in the clinical evaluation of patients. PMID- 26876909 TI - Exploring the relationship between nature sounds, connectedness to nature, mood and willingness to buy sustainable food: A retail field experiment. AB - Nature sounds are increasingly used by some food retailers to enhance in-store ambiance and potentially even influence sustainable food choices. An in-store, 2 * 3 between-subject full factorial experiment conducted on 627 customers over 12 days tested whether nature sound directly and indirectly influenced willingness to buy (WTB) sustainable foods. The results show that nature sounds positively and directly influence WTB organic foods in groups of customers (men) that have relatively low initial intentions to buy. Indirectly, we did not find support for the effect of nature sound on influencing mood or connectedness to nature (CtN). However, we show that information on the product's sustainability characteristics moderates the relationship between CtN and WTB in certain groups. Namely, when CtN is high, sustainability information positively moderated WTB both organic and climate friendly foods in men. Conversely, when CtN was low, men expressed lower WTB organic and climate friendly foods than identical, albeit conventionally labelled products. Consequently, our study concludes that nature sounds might be an effective, yet subtle in-store tool to use on groups of consumers who might otherwise respond negatively to more overt forms of sustainable food information. PMID- 26876911 TI - Eating less from bigger packs: Preventing the pack size effect with diet primes. AB - An increase in the package size of food has been shown to lead to an increase in energy intake from this food, the so-called pack size effect. Previous research has shown that providing diet-concerned individuals with a reminder, or prime, of their dieting goal can help them control their consumption. Here, we investigated if providing such a prime is also effective for reducing the magnitude of the pack size effect. We conducted two experiments in which the cover of a dieting magazine (Experiment 1) and diet-related commercials (Experiment 2) served as diet goal primes. Both experiments had a 2 (pack size: small vs. large) * 2 (prime: diet vs. control) * 2 (dietary restraint: high vs. low) between participants design. We measured expected consumption of four snack foods in Experiment 1 (N = 477), and actual consumption of M&M's in Experiment 2 (N = 224). Results showed that the diet prime reduced the pack size effect for both restrained and unrestrained eaters in Experiment 1 and for restrained eaters only in Experiment 2. Although effect sizes were small, these findings suggest that a diet prime motivates restrained eaters to limit their consumption, and as a result the pack size has less influence on the amount consumed. We discuss limitations of this research as well as potential avenues for further research and theoretical and practical implications. PMID- 26876912 TI - The prevalence of leucocyte alloantibodies in blood donors from South China. AB - BACKGROUND: Several studies had demonstrated that leucocyte antibodies including anti-human leucocyte antigen (anti-HLA) antibodies (class I and class II) and anti-human neutrophil antigen (anti-HNA) antibodies (HNA-1, -2 and -3) present in the blood products are responsible for transfusion-related acute lung injury (TRALI). Therefore, selection of blood products exclusive of anti-HLA and anti HNA antibodies may lower the risk of TRALI reaction. However, the prevalence of leucocyte antibodies among blood donors in China is currently not known. STUDY DESIGN AND METHODS: Blood samples were collected from 454 male and 560 female donors (143 nulliparous and 417 multiparous female). HLA class I and II antibodies were analyzed by bead assays. Anti-HNA-1 and -2 antibodies were screened by the LABScreen assay (One Lambda Inc.), and HNA-3 were detected by antigen capture assay, and confirmed by the granulocyte agglutination test (GAT). RESULTS: Screening of the total cohort showed higher prevalence of HLA antibodies in female compared with male donors (19.64 vs. 4.63%). We found antibodies against HLA class I (13.21%) and HLA class II (11.43%) in 560 female donors. The most frequent antibodies against HLA class I and II in parous females (n = 69) reacted with were A*11 (28.81%), B*07 (42.37%), Cw*07 (20.34%) and DRB1*04 (40.43%) molecules. Among 778 donors (randomly selected from 1014 donors), we found three donors with neutrophil reactive antibodies, two against HNA-2 and one without known specificity. Anti-HNA-3 antibodies were not found so far. CONCLUSION: In this study, we found alloimmunization against HLA class I, II and HNA in 4.63, 24.70 and 0.39%, respectively, in our female blood donors, indicating that the use of plasma containing blood products from parous female blood donors without HLA antibodies pre-testing may increase the risk of TRALI reaction. Although immunization against HNA seems to be a rare event in China, further observation is necessary to decide the necessity of HNA antibodies screening in our blood donors. PMID- 26876910 TI - Confirmatory factor analysis of the Infant Feeding Styles Questionnaire in Latino families. AB - BACKGROUND: Parent feeding practices affect risk of obesity in children. Latino children are at higher risk of obesity than the general population, yet valid measure of feeding practices, one of which is the Infant Feeding Styles Questionnaire (IFSQ), have not been formally validated in Spanish. OBJECTIVE: To validate the IFSQ among Latino families, we conducted confirmatory factor analysis of pressuring, restrictive, and responsive feeding constructs from the IFSQ. DESIGN/METHODS: The IFSQ was administered at the 12-month visit in the Greenlight study, a multi-center cluster randomized trial to prevent obesity. Parents were included if they were of Latino origin (n = 303) and completed an English or Spanish language modified IFSQ (without the indulgence construct). Scores from nine sub-constructs of the IFSQ were compared between English and Spanish language versions. We tested reliability with Cronbach's alpha coefficients and performed confirmatory factor analysis to examine factor loadings and goodness of fit characteristics, modifying constructs to achieve best fit. RESULTS: Of 303 parents completing the IFSQ, 84% were born outside the US, and 74% completed the IFSQ in Spanish. Reliability coefficients ranged from 0.28 to 0.61 for the laissez-faire sub-constructs and from 0.58 to 0.83 for the pressuring, restrictive, and responsive sub-constructs. Results for all coefficients were similar between participants responding to an English and Spanish version of the IFSQ. Goodness of fit indices ranged from CFI 0.82-1 and RMSEA 0.00-0.31, and the model performed best in pressuring-soothing (CFI 1.0, RMSEA 0.00) and restrictive-amount (CFI 0.98, RMSEA 0.1) sub-constructs. CONCLUSIONS: In a sample of Latino families, pressuring, restrictive, and responsive constructs performed well. The modified IFSQ in both English and Spanish-speaking Latino families may be used to assess parenting behaviors related to early obesity risk in this at-risk population. PMID- 26876913 TI - Cognitive impairment in late-life bipolar disorder is not associated with Alzheimer's disease pathological signature in the cerebrospinal fluid. AB - OBJECTIVES: Cognitive impairment is a common feature of late-life bipolar disorder (BD). Yet, there is limited information on the biological mechanisms associated with this process. It is uncertain whether cognitively impaired patients with BD may present the Alzheimer's disease (AD) bio-signature in the cerebrospinal fluid (CSF), defined as a combination of low concentrations of the amyloid-beta peptide (Abeta1-42 ) and high concentrations of total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau). In this study, we sought to determine whether cognitive impairment in elderly patients with BD is associated with the AD CSF bio-signature. METHODS: Seventy-two participants were enrolled in the study. The test group comprised older adults with BD and mild cognitive impairment (BD-MCI; n = 16) and the comparison groups comprised patients with dementia due to AD (n = 17), patients with amnestic MCI (aMCI; n = 14), and cognitively healthy older adults (control group; n = 25). CSF samples were obtained by lumbar puncture and concentrations of Abeta1-42 , T-tau and P-tau were determined. RESULTS: CSF concentrations of all biomarkers were significantly different in the AD group compared to all other groups, but did not differentiate BD-MCI subjects from aMCI subjects and controls. BD-MCI patients had a non significant reduction in CSF Abeta1-42 compared to controls, but this was still higher than in the AD group. Concentrations of T-tau and P-tau in BD-MCI patients were similar to those in controls, and significantly lower than those in AD. CONCLUSIONS: Cognitively impaired patients with BD do not display the so-called AD bio-signature in the CSF. We therefore hypothesize that cognitive deterioration in BD is not associated with the classical pathophysiological mechanisms observed in AD, i.e., amyloid deposition and hyperphosphorylation of microtubule-associated tau protein. PMID- 26876915 TI - Molecular mechanisms underlying chemopreventive potential of curcumin: Current challenges and future perspectives. AB - In recent years, natural compounds have received considerable attention in preventing and curing most dreadful diseases including cancer. The reason behind the use of natural compounds in chemoprevention is associated with fewer numbers of side effects than conventional chemotherapeutics. Curcumin (diferuloylmethane, PubMed CID: 969516), a naturally occurring polyphenol, is derived from turmeric, which is used as a common Indian spice. It governs numerous intracellular targets, including proteins involved in antioxidant response, immune response, apoptosis, cell cycle regulation and tumor progression. A huge mass of available studies strongly supports the use of Curcumin as a chemopreventive drug. However, the main challenge encountered is the low bioavailability of Curcumin. This extensive review covers various therapeutic interactions of Curcumin with its recognized cellular targets involved in cancer treatment, strategies to overcome the bioavailability issue and adverse effects associated with Curcumin consumption. PMID- 26876914 TI - Manganese protects against the effects of alcohol on hypothalamic puberty-related hormones. AB - AIMS: Since manganese (Mn) is capable of stimulating the hypothalamic-pituitary unit and advancing female puberty, we assessed the possibility that this element might overcome some of the detrimental effects of prepubertal alcohol (ALC) exposure on the hypothalamic control of pituitary function. MAIN METHODS: Rats received either saline or Mn (10mg/kg) daily by gastric gavage from day 12 to day 31. After weaning, all rats were provided Lab Chow diet ad libitum until day 27 when they began receiving either the Bio Serv control or ALC diet regime. On day 31, the medial basal hypothalamus (MBH) was collected to assess luteinizing hormone-releasing hormone (LHRH) and cyclooxygenase 2 (COX2) protein levels. Release of prostaglandin-E2 (PGE2), LHRH and serum luteinizing hormone (LH) were also assessed. Other animals were not terminated on day 31, but remained in study to assess timing of puberty. KEY FINDINGS: Short-term ALC exposure caused elevated hypothalamic LHRH content, suggesting an inhibition in peptide release, resulting in a decrease in LH. Both actions of ALC were reversed by Mn supplementation. COX2 synthesis, as well as PGE2 and LHRH release were suppressed by ALC exposure, but Mn supplementation caused an increase in COX2 synthesis and subsequent PGE2 and LHRH release in the presence of ALC. Mn supplementation also ameliorated the action of ALC to delay puberty. SIGNIFICANCE: These results suggest that low level Mn supplementation acts to protect the hypothalamus from some of the detrimental effects of ALC on puberty-related hormones. PMID- 26876916 TI - Therapeutic potential of chalcones as cardiovascular agents. AB - Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. PMID- 26876917 TI - Synergetic cholesterol-lowering effects of main alkaloids from Rhizoma Coptidis in HepG2 cells and hypercholesterolemia hamsters. AB - AIMS: Hyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids. MAIN METHODS: The cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3 methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured. KEY FINDING: As compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation. SIGNIFICANCE: Our results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia. PMID- 26876918 TI - Cardiovascular responses elicited by continuous versus intermittent electrical stimulation of the aortic depressor nerve in conscious rats. AB - AIMS: Short-term (seconds or minutes) continuous electrical activation of the aortic depressor nerve (ADN) in conscious rats has been successfully used to investigate baroafferent function in experimental hypertension, heart failure, and peripheral inflammation. The aim of this study was to characterize the hemodynamic responses elicited by longer periods (60min) of continuous or intermittent electrical baroreflex activation. MAIN METHODS: Wistar rats were implanted with an electrode around the left ADN and a catheter into a femoral artery. The systolic, diastolic and mean arterial pressure and heart rate were recorded in subjects randomly assigned to continuous or intermittent electrical stimulation. The time-course of cardiovascular responses in conscious rats was examined during longer-term (60min) continuous (n=6) or intermittent (5s ON/3s OFF; n=10) electrical stimulation (0.5mA; 0.25ms; 30Hz) of the ADN. KEY FINDINGS: The prompt (20s) hypotensive response was greater under continuous stimulation, but no difference was detected in the bradycardic response. The hypotensive response was sustained only by continuous stimulation while no sustained bradycardia was observed in either protocol. SIGNIFICANCE: These findings indicate that continuous stimulation of the ADN is more effective in reducing arterial pressure over a longer period (60min) of stimulation. Nevertheless, both protocols - continuous or intermittent - were unable to elicit a sustained bradycardia. PMID- 26876919 TI - Physical, emotional, and cognitive effort discounting in gain and loss situations. AB - Evidence suggests that factors associated with obtaining a reward, such as the probability of receiving it, or temporal delays, could influence the reward's subjective value. Several studies have suggested that increasing the effort required decreases the subjective value of a reward. Nevertheless, the nature of effort that results in discounting, discounting in a loss situation, and individual consistency in effort aversion across different types of effort have all remained unclear. Therefore, the present study examined whether physical, emotional, and cognitive efforts induce discounting of subjective reward value under two hypothetical situations. In the gain situation, participants made a choice about engaging in effortful work to obtain a reward, whereas in the loss situation they paid a reward to another person to do the work. The results demonstrated that increasing physical, emotional, and cognitive effort caused discounting of the subjective reward value in both situations. Additionally, the results suggested a relatively high degree of individual consistency in effort aversion in each situation, and a moderate degree of consistency across the two situations. PMID- 26876921 TI - Trends and concepts in post-mastectomy breast reconstruction. AB - A number of factors have contributed to a paradigm shift in US post-mastectomy breast reconstruction. The increasing numbers of contralateral prophylactic mastectomies strongly correlated to a rise in implant-based reconstructions. Autologous reconstruction, however, has faced a number of barriers including technically complicated perforator flaps and declining reimbursements. As such, a market concentration has developed within high volume microsurgical centers. As more patients receive radiation, the timing and method of reconstruction has become a controversial topic. J. Surg. Oncol. 2016;113:891-894. (c) 2016 Wiley Periodicals, Inc. PMID- 26876922 TI - Psoriasis with verrucous appearance. PMID- 26876923 TI - Intensity modulated radiation therapy for recurrent ovarian cancer refractory to chemotherapy. AB - OBJECTIVE: To evaluate local control, survival outcomes, and toxicity after intensity modulated radiotherapy (IMRT) for recurrent chemorefractory ovarian cancer. METHODS: Between 2006 and 2014, 33 patients were treated with IMRT for recurrent ovarian cancer. Patients received a median of 3 chemotherapy regimens prior to IMRT (range, 1-12) with 11 (33%) undergoing concurrent therapy. Local control (LC), recurrence free survival (RFS), and overall survival (OS) were calculated via Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Impact of patient characteristics on outcomes was evaluated via Cox's proportional hazard model. RESULTS: Median follow up was 23.7 months. Forty-nine sites were treated to a median dose of 5040cGy (range, 4500-7000). Nine (18%) of the 49 sites had in field failures. Two year actuarial LC, RFS, and OS were 82%, 11%, and 63%, respectively. Seventeen patients had both a pre and post-treatment FDG-PET/CT; 6 (35%) had a complete metabolic response while 11 (65%) had a partial metabolic response. Acute >= grade 3 gastrointestinal (GI) toxicities occurred in 2 (6%) patients, late >= grade 3 GI toxicities occurred in 12 (36%), acute >= grade 3 hematological toxicities occurred in 5 (15%) and late >= grade 3 hematological toxicities occurred in 14 (42%). CONCLUSIONS: IMRT for recurrent chemorefractory ovarian cancer is associated with excellent local control and limited radiation related toxicity. Future studies will be required to determine which subpopulation will benefit most from IMRT and whether alternative techniques such as stereotactic body radiotherapy may be feasible. PMID- 26876920 TI - ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types. AB - Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID- 26876925 TI - Barrier crossing in small avian migrants: individual tracking reveals prolonged nocturnal flights into the day as a common migratory strategy. AB - Over decades it has been unclear how individual migratory songbirds cross large ecological barriers such as seas or deserts. By deploying light-level geolocators on four songbird species weighing only about 12 g, we found that these otherwise mainly nocturnal migrants seem to regularly extend their nocturnal flights into the day when crossing the Sahara Desert and the Mediterranean Sea. The proportion of the proposed diurnally flying birds gradually declined over the day with similar landing patterns in autumn and spring. The prolonged flights were slightly more frequent in spring than in autumn, suggesting tighter migratory schedules when returning to breeding sites. Often we found several patterns for barrier crossing for the same individual in autumn compared to the spring journey. As only a small proportion of the birds flew strictly during the night and even some individuals might have flown non-stop, we suggest that prolonged endurance flights are not an exception even in small migratory species. We emphasise an individual's ability to perform both diurnal and nocturnal migration when facing the challenge of crossing a large ecological barrier to successfully complete a migratory journey. PMID- 26876927 TI - Imbalance of Gastrointestinal Microbiota in the Pathogenesis of Helicobacter pylori-Associated Diseases. AB - The development of new nucleotide sequencing techniques and advanced bioinformatics tools has opened the field for studying the diversity and complexity of the gastrointestinal microbiome independent of traditional cultural methods. Owing largely to the gastric acid barrier, the human stomach was long thought to be sterile. The discovery of Helicobacter pylori, the gram-negative bacterium that infects upwards of 50% of the global population, has started a major paradigm shift in our understanding of the stomach as an ecologic niche for bacteria. Recent sequencing analysis of gastric microbiota showed that H. pylori was not alone and the interaction of H. pylori with those microorganisms might play a part in H. pylori-associated diseases such as gastric cancer. In this review, we summarize the available literature about the changes of gastrointestinal microbiota after H. pylori infection in humans and animal models, and discuss the possible underlying mechanisms including the alterations of the gastric environment, the secretion of hormones and the degree of inflammatory response. In general, information regarding the composition and function of gastrointestinal microbiome is still in its infancy, future studies are needed to elucidate whether and to what extent H. pylori infection perturbs the established microbiota. It is assumed that clarifying the role of gastrointestinal communities in H. pylori-associated diseases will provide an opportunity for translational application as a biomarker for the risk of serious H. pylori diseases and perhaps identify specific organisms for therapeutic eradication. PMID- 26876926 TI - Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder. AB - BACKGROUND: The vast majority of functional neuroimaging studies in posttraumatic stress disorder (PTSD) have examined the amygdala as a unitary structure. However, an emerging body of studies indicates that separable functions are subserved by discrete amygdala subregions. The basolateral subdivision (BLA), as compared with the centromedial amygdala (CMA), plays a unique role in learning and memory-based processes for threatening events, and alterations to the BLA have been implicated in the pathogenesis of PTSD. We assessed whether PTSD is associated with differential involvement of the BLA versus the CMA during successful encoding of emotionally charged events. METHODS: Participants with PTSD (n=11) and a trauma-exposed comparison (TEC) group (n=11) viewed a series of photos that varied in valence (negative versus positive) and arousal (high versus low) while undergoing functional magnetic resonance imaging (fMRI). Subsequently, participants completed an old/new recognition memory test. RESULTS: Using analytic methods based on probabilistic cytoarchitectonic mapping, PTSD was associated with greater activation of the BLA, as compared to the CMA, during successful encoding of negative scenes, a finding which was not observed in the TEC group. Moreover, this memory-related activity in the BLA independently predicted PTSD status. Contrary to hypotheses, there was no evidence of altered BLA activity during memory encoding of high arousing relative to low arousing scenes. CONCLUSIONS: Task-related brain activation in PTSD does not appear to be consistent across the entire amygdala. Importantly, memory-related processing of negative information in PTSD is associated with preferential recruitment of the BLA. PMID- 26876928 TI - The effect of polymer size and charge of molecules on permeation through synovial membrane and accumulation in hyaline articular cartilage. AB - The treatment of joint related diseases often involves direct intra-articular injections. For rational development of novel delivery systems with extended residence time in the joint, detailed understanding of transport and retention phenomena within the joint is mandatory. This work presents a systematic study on the in vitro permeation, penetration and accumulation of model polymers with differing charges and molecular weights in bovine joint tissue. Permeation experiments with bovine synovial membrane were performed with PEG polymers (6-200 kDa) and methylene blue in customized diffusion chambers. For polyethylene glycol, 2-fold (PEG 6 kDa), 3-fold (PEG 10 kDa) and 13-fold (PEG 35 kDa) retention by the synovial membrane in reference to the small molecule methylene blue was demonstrated. No PEG 200 kDa was found in the acceptor in detectable amounts after 48 h. This showed the potential for a distinct extension of joint residence times by increasing molecular weights. In addition, experiments with bovine cartilage tissue were conducted. The ability for positively charged, high molecular weight chitosans and HEMA-Co-TMAP (HCT) polymers (up to 233 kDa) to distribute throughout the entire cartilage matrix was demonstrated. In contrast, a distribution into cartilage was not observed for neutral PEG polymers (6-200 kDa). Furthermore, the positive charge density of different compounds (chitosan, HEMA-Co-TMAP, methylene blue, MSC C1 (neutral NCE) and MSC D1 (positively charged NCE) was found to correlate with their accumulation in bovine cartilage tissue. In summary, the results offer pre-clinical in vitro data, indicating that the modification of molecular size and charge of a substance has the potential to decelerate its clearance through the synovial membrane and to promote accumulation inside the cartilage matrix. PMID- 26876929 TI - Novel indole sulfides as potent HIV-1 NNRTIs. AB - In a previous communication we described a series of indole based NNRTIs which were potent inhibitors of HIV replication, both for the wild type and K103N strains of the virus. However, the methyl ether functionality on these compounds, which was crucial for potency, was susceptible to acid promoted indole assisted SN1 substitution. This particular problem did not bode well for an orally bioavailable drug. Here we describe bioisosteric replacement of this problematic functional group, leading to a series of compounds which are potent inhibitors of HIV replication, and are acid stable. PMID- 26876924 TI - Functional neuroanatomy of amygdalohippocampal interconnections and their role in learning and memory. AB - The amygdalar nuclear complex and hippocampal/parahippocampal region are key components of the limbic system that play a critical role in emotional learning and memory. This Review discusses what is currently known about the neuroanatomy and neurotransmitters involved in amygdalo-hippocampal interconnections, their functional roles in learning and memory, and their involvement in mnemonic dysfunctions associated with neuropsychiatric and neurological diseases. Tract tracing studies have shown that the interconnections between discrete amygdalar nuclei and distinct layers of individual hippocampal/parahippocampal regions are robust and complex. Although it is well established that glutamatergic pyramidal cells in the amygdala and hippocampal region are the major players mediating interconnections between these regions, recent studies suggest that long-range GABAergic projection neurons are also involved. Whereas neuroanatomical studies indicate that the amygdala only has direct interconnections with the ventral hippocampal region, electrophysiological studies and behavioral studies investigating fear conditioning and extinction, as well as amygdalar modulation of hippocampal-dependent mnemonic functions, suggest that the amygdala interacts with dorsal hippocampal regions via relays in the parahippocampal cortices. Possible pathways for these indirect interconnections, based on evidence from previous tract tracing studies, are discussed in this Review. Finally, memory disorders associated with dysfunction or damage to the amygdala, hippocampal region, and/or their interconnections are discussed in relation to Alzheimer's disease, posttraumatic stress disorder (PTSD), and temporal lobe epilepsy. (c) 2016 Wiley Periodicals, Inc. PMID- 26876930 TI - Synthesis and anti-inflammatory activity evaluation of a novel series of 6 phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide derivatives. AB - The transcription factor nuclear factor-kappaB (NF-kappaB) controls many physiological processes including inflammation, immunity, and apoptosis. In this study, a novel series of 6-phenoxy-[1,2,4]triazolo[3,4-a]phthalazine-3 carboxamide derivatives were synthesized as potent anti-inflammatory agents, which acted on tumor necrosis factor (TNF-alpha) as inhibitors of NF-kappaB activation. We showed that compounds 6h (6-(2,4-dichlorophenoxy) [1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) and 6i (6-(3-tolyloxy) [1,2,4]triazolo[3,4-a]phthalazine-3-carboxamide) showed more prominent anti inflammatory activity than other compounds, with similar activities as the reference drug dihydrotanshinone; compound 6i showed the lowest cellular toxicity among the tested compounds. In vivo evaluation of the anti-inflammatory activity showed that compound 6i exhibited excellent anti-inflammatory activity with 58.19% inhibition at 50mg/kg intraperitoneal (i.p.), with equal efficacy as the positive control indomethacin (100mg/kg i.p.; 59.21% inhibition). PMID- 26876931 TI - Optimization of N'-(arylsulfonyl)pyrazoline-1-carboxamidines by exploiting a novel interaction site in the 5-HT6 antagonistic binding pocket. AB - The discovery of non-basic N'-(arylsulfonyl)pyrazoline-1-carboxamidines as 5-HT6 antagonists with unique structural features was recently disclosed. Here we describe how this structural class was further developed by addressing an unexplored interaction site of the 5-HT6 receptor. Compound 13 resulting from this effort is a highly potent and selective 5-HT6 antagonist with improved metabolic stability. It is furthermore devoid of hERG affinity. Despite its modest CNS/plasma ratio, a high brain free fraction ensured substantial exposure to allow for rodent cognition studies. PMID- 26876932 TI - Biocatalyzed synthesis of difuranosides and their ability to trigger production of TNF-alpha. AB - Transglycosylation reactions biocatalyzed by the native arabinofuranosidase Araf51 and using d-galactosyl, d-fucosyl and 6-deoxy-6-fluoro-D-galactosyl derivatives as donors and acceptors provided di-to pentahexofuranosides. The immunostimulatory potency of these compounds, and more especially their ability to induce production of TNF-alpha, was evaluated on the murine macrophage cell line, Raw 264.7. The results obtained showed concentration-dependent and most importantly, structure-dependent responses. Interestingly, oligoarabinofuranosides belonging to the oligopentafuranoside family displayed concentration-, chain length and aglycon-dependent bioactivities irrespective of their fine chemical variations. Thus, neo-oligofuranosides in D-Galf series, as well as their D-Fucf and 6-fluorinated counterparts are indeed potential sources of immunostimulating agents. PMID- 26876934 TI - Retraction. Clc-2 knockout attenuated experimental temporal lobe epilepsy in mice by tonic inhibition mediated by GABAA receptors. AB - Temporal lobe epilepsy (TLE), the most prevalent form of epilepsy, is often associated with drug-resistant seizures. In TLE, altered function of gamma aminobutyric acid (GABA)A receptors (GABAARs) results in potentiation of excitatory and/or failure of inhibitory neurotransmission, which contributes to seizure induction and propagation. Our previous study suggested that chloride channel-2 (Clc-2) contributed to chronically elevated tonic inhibition mediated by GABAARs in a rat model of TLE. In the present study, we used Clc-2 knockout mice to investigate further the role of Clc-2 and its interaction with tonic GABAergic inhibition in a model of TLE. The results revealed that knockout of Clc 2 decreased tonic seizure protection, latency of clonic seizure, seizure threshold and mortality protection in mice. Clc-2 knockout decreased the action potential (AP)peak and APthreshold, Clc-2 currents and GABAAR-mediated tonic inhibition in CA1 pyramidal neurons. Thus, the voltage-gated chloride channel Clc 2, which was functionally upregulated in CA1 pyramidal cells after seizures, may provide protection against TLE by its regulation of action potentials, Clc-2 currents and GABAARs in the CA1 region of the hippocampus. PMID- 26876933 TI - Suppression of Mcl-1 induces apoptosis in mouse peritoneal macrophages infected with Mycobacterium tuberculosis. AB - The effect of myeloid cell leukemia-1 (Mcl-1) inhibition on apoptosis of peritoneal macrophages in mice infected with Mycobacterium tuberculosis was investigated and the primary signaling pathway associated with the transcriptional regulation of Mcl-1 was identified. Real-time PCR and western blotting indicated that Mcl-1 transcript and protein expression are upregulated during infection with virulent M. tuberculosis H37Rv and Xinjiang strains but not with attenuated M. tuberculosis strain H37Ra or Bacillus Calmette-Guerin. Mcl-1 transcript and protein expression were downregulated by specific inhibitors of the Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways (AG490, PD98059 and LY294002, respectively). The strongest inhibitor of Mcl-1 expression was PD98059, the MAPK inhibitor. Flow cytometry demonstrated that the rate of apoptosis in peritoneal macrophages is significantly higher in mice infected with M. tuberculosis and the rate of apoptosis is correlated with the virulence of the strain of M. tuberculosis. Apoptosis was found to be upregulated by AG490, PD98059 and LY294002, whereas inhibition of the MAPK pathway sensitized the infected macrophages to apoptosis. Taken together, these results suggest that specific downregulation of Mcl-1 significantly increases apoptosis of peritoneal macrophages and that the MAPK signaling pathway is the primary mediator of Mcl-1 expression. PMID- 26876935 TI - Effects of 1-cyclohexyl- and 1-cyclohexyl-N-propargyl-1,2,3,4 tetrahydroisoquinoline on dopaminergic spontaneous discharge in nigral neurons of rats. AB - 1,2,3,4-Tetrahydroisoquinoline (TIQ) and some of its derivatives, such as 1 benzyl-TIQ and 1-methyl-TIQ, are endogenously present in human brain and are thought to contribute to induction or prevention of Parkinson's disease. In the present study, we estimated the effects of the artificially synthesized TIQ derivatives 1-cyclohexyl-TIQ (1-cHex-TIQ) and 1-cyclohexyl-N-propargyl-TIQ (1 cHex-N-proTIQ) on spontaneous nigral dopaminergic discharge in rats. Low to middle doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced a transient and significant, but not relatively potent, increase in the firing rate, followed by a sustained decrease with higher doses. 1-cHex-TIQ increased the firing frequency at low and high doses. In contrast, 1-cHex-N-proTIQ had no effects on spontaneous firing. Although intraperitoneal pretreatment with 1-cHex TIQ did not inhibit this MPTP-induced decrease in firing, pretreatment with 1 cHex-N-proTIQ significantly depressed this decreased firing in a dose-dependent and long-lasting manner. Selegiline, a monoamine oxidase type B inhibitor that is used as a therapeutic drug for Parkinson's disease, also significantly inhibited the decrease in dopaminergic spontaneous firing induced by MPTP, but the effect was transient. These results suggest that although the decrease in firing induced by 1-cHex-TIQ is clearly more potent compared to that induced by MPTP, its effect is eliminated by adding an N-propargyl functional group. The antagonizing effect of 1-cHex-N-proTIQ on MPTP-induced firing loss may be exerted by a different mechanism than that of selegiline. PMID- 26876936 TI - Stem cell secretome-rich nanoclay hydrogel: a dual action therapy for cardiovascular regeneration. AB - A nanocomposite hydrogel with photocrosslinkable micro-porous networks and a nanoclay component was successfully prepared to control the release of growth factor-rich stem cell secretome. The proven pro-angiogenic and cardioprotective potential of this new bioactive system provides a valuable therapeutic platform for cardiac tissue repair and regeneration. PMID- 26876937 TI - Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. AB - The regulatory role of N(6)-methyladenosine (m(6)A) and its nuclear binding protein YTHDC1 in pre-mRNA splicing remains an enigma. Here we show that YTHDC1 promotes exon inclusion in targeted mRNAs through recruiting pre-mRNA splicing factor SRSF3 (SRp20) while blocking SRSF10 (SRp38) mRNA binding. Transcriptome assay with PAR-CLIP-seq analysis revealed that YTHDC1-regulated exon-inclusion patterns were similar to those of SRSF3 but opposite of SRSF10. In vitro pull down assay illustrated a competitive binding of SRSF3 and SRSF10 to YTHDC1. Moreover, YTHDC1 facilitates SRSF3 but represses SRSF10 in their nuclear speckle localization, RNA-binding affinity, and associated splicing events, dysregulation of which, as the result of YTHDC1 depletion, can be restored by reconstitution with wild-type, but not m(6)A-binding-defective, YTHDC1. Our findings provide the direct evidence that m(6)A reader YTHDC1 regulates mRNA splicing through recruiting and modulating pre-mRNA splicing factors for their access to the binding regions of targeted mRNAs. PMID- 26876938 TI - Deubiquitination and Activation of AMPK by USP10. AB - The AMP-activated protein kinase (AMPK) is the master regulator of metabolic homeostasis by sensing cellular energy status. When intracellular ATP levels decrease during energy stress, AMPK is initially activated through AMP or ADP binding and phosphorylation of a threonine residue (Thr-172) within the activation loop of its kinase domain. Here we report a key molecular mechanism by which AMPK activation is amplified under energy stress. We found that ubiquitination on AMPKalpha blocks AMPKalpha phosphorylation by LKB1. The deubiquitinase USP10 specifically removes ubiquitination on AMPKalpha to facilitate AMPKalpha phosphorylation by LKB1. Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10. Thus, USP10 and AMPK form a key feedforward loop ensuring amplification of AMPK activation in response to fluctuation of cellular energy status. Disruption of this feedforward loop leads to improper AMPK activation and multiple metabolic defects. PMID- 26876940 TI - Optimizing HCV treatment - Moving beyond the cost conundrum. PMID- 26876939 TI - mTORC1 Coordinates Protein Synthesis and Immunoproteasome Formation via PRAS40 to Prevent Accumulation of Protein Stress. AB - Reduction of translational fidelity often occurs in cells with high rates of protein synthesis, generating defective ribosomal products. If not removed, such aberrant proteins can be a major source of cellular stress causing human diseases. Here, we demonstrate that mTORC1 promotes the formation of immunoproteasomes for efficient turnover of defective proteins and cell survival. mTORC1 sequesters precursors of immunoproteasome beta subunits via PRAS40. When activated, mTORC1 phosphorylates PRAS40 to enhance protein synthesis and simultaneously to facilitate the assembly of the beta subunits for forming immunoproteasomes. Consequently, the PRAS40 phosphorylations play crucial roles in clearing aberrant proteins that accumulate due to mTORC1 activation. Mutations of RAS, PTEN, and TSC1, which cause mTORC1 hyperactivation, enhance immunoproteasome formation in cells and tissues. Those mutations increase cellular dependence on immunoproteasomes for stress response and survival. These results define a mechanism by which mTORC1 couples elevated protein synthesis with immunoproteasome biogenesis to protect cells against protein stress. PMID- 26876941 TI - pNEB193-derived suicide plasmids for gene deletion and protein expression in the methane-producing archaeon, Methanosarcina acetivorans. AB - Gene deletion and protein expression are cornerstone procedures for studying metabolism in any organism, including methane-producing archaea (methanogens). Methanogens produce coenzymes and cofactors not found in most bacteria, therefore it is sometimes necessary to express and purify methanogen proteins from the natural host. Protein expression in the native organism is also useful when studying post-translational modifications and their effect on gene expression or enzyme activity. We have created several new suicide plasmids to complement existing genetic tools for use in the methanogen, Methanosarcina acetivorans. The new plasmids are derived from the commercially available Escherichia coli plasmid, pNEB193, and cannot replicate autonomously in methanogens. The designed plasmids facilitate markerless gene deletion, gene transcription, protein expression, and purification of proteins with cleavable affinity tags from the methanogen, M. acetivorans. PMID- 26876943 TI - The Prevalence of Positive Findings on Metal Artifact Reduction Sequence Magnetic Resonance Imaging in Metal-on-Metal Total Hip Arthroplasty. AB - BACKGROUND: We sought to assess the prevalence of soft tissue changes seen on magnetic resonance imaging (MRI) after metal-on-metal (MOM) total hip arthroplasty (THA) and determine if the presence of pseudotumors was associated with metal ion levels, acetabular cup position, outcomes scores, and femoral head size. METHODS: After receiving an institutional review board exemption for secondary data analysis, we performed a cross-sectional study identifying 55 patients (55 hips) that underwent primary THA with a MOM articulation and had subsequent MRI imaging between February 2013 and February 2014 at a single academic medical center. RESULTS: Twenty-four patients (44%) had no evidence of pseudotumors, 27 (49%) had type I pseudotumors, and 4 (7%) were classified as having type II pseudotumors. The presence and severity of pseudotumors were associated with higher serum chromium levels (P = .043). Neither acetabular inclination nor acetabular version was associated with the presence of pseudotumors, the severity of pseudotumors, or elevated serum metal ion levels (all P > .05). Increased metal ion levels were associated with lower Harris Hip Score and higher Harris Hip Score pain subscores (all P < .05). CONCLUSION: In conclusion, pseudotumors on metal artifact reduction sequencing MRI may be present in both symptomatic and asymptomatic MOM THAs. Surgeons should therefore exercise caution in placing too much emphasis on isolated studies such as cross sectional imaging. Instead, a structured approach to evaluation of MOM arthroplasty should be followed. PMID- 26876942 TI - pBR322 vectors having tetracycline-dependent replication. AB - Few Escherichia coli cloning vectors are available that can both be stably maintained and efficiently cured. One such vector is pAM34, a pBR332 derivative constructed by Gil and Bouche (1991). Replication of this plasmid is driven by the lacZYA promoter under control of a gratuitous inducer. However, lac operator repressor interactions are also used to regulate many expression systems which limit the utility of pAM34. In this report pAM34 has been modified by replacement of the lac regulatory elements with those of the transposon Tn10 tetracycline resistance module. This resulted in medium copy number plasmids that are dependent on the presence of tetracycline (or less satisfactorily, anhydrotetracycline) for replication. The tetracycline-dependent plasmids are rapidly lost in the absence of tetracycline and plasmid loss is markedly accelerated when the host strain expresses a tetracycline efflux pump. PMID- 26876944 TI - Does the Canal Fill Ratio and Femoral Morphology of Asian Females Influence Early Radiographic Outcomes of Total Hip Arthroplasty With an Uncemented Proximally Coated, Tapered-Wedge Stem? AB - BACKGROUND: Noncement femoral fixation in total hip arthroplasty (THA) has been gaining popularity. However, owing to the numerous varieties of uncemented stems and differing types of femoral stem morphology, it is unclear whether the clinical outcomes of all uncemented stems are equal. The aim of this study was to investigate the relationships between canal fill ratio and femoral morphology and early radiologic outcomes in Japanese patients who underwent THA with an uncemented proximally hydroxyapatite-coated, tapered-wedge stem. METHODS: We retrospectively reviewed 103 patients who had undergone THA using a single proximally coated tapered-wedge stem. The relationships between canal fill ratio and femoral morphology and early radiologic outcomes after THA with those stem were investigated. RESULTS: Eighty-one hips were analyzed after inclusion and exclusion criteria were applied. Failed osteointegration proximally was observed in 4 hips (4.9%). Canal flare index was significantly greater in hips with failed osteointegration than in those with successful osteointegration (P = .009). Distal hypertrophy was observed in 14 hips (17.3%). Proximal-distal matching ratio was significantly lower in hips with distal hypertrophy than in those without (P = .01). Canal fill ratio at 2 cm above the lesser trochanter was smaller in hips with failed osteointegration and distal hypertrophy than in those without (P = .02). CONCLUSION: Suboptimal radiologic changes were seen with greater distal fill with smaller proximal fill and with a narrow femoral canal. It is important to select the stem that can achieve the original concept of intended primary and secondary fixation areas. PMID- 26876945 TI - How do we transfuse blood components in cirrhotic patients undergoing gastrointestinal procedures? AB - The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center. PMID- 26876946 TI - A Human Open Field Test Reveals Thigmotaxis Related to Agoraphobic Fear. AB - BACKGROUND: Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia. METHODS: A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square. RESULTS: Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia. CONCLUSIONS: This study is the first to our knowledge to verify the translational validity of the OFT and to reveal that thigmotaxis, an evolutionarily adaptive behavior shown by most species, is related to agoraphobia, a pathologic fear of open spaces, and anxiety sensitivity, a risk factor for agoraphobia. PMID- 26876948 TI - Notch-dependent EMT is attenuated in patients with aortic aneurysm and bicuspid aortic valve. AB - Bicuspid aortic valve is the most common congenital heart malformation and the reasons for the aortopathies associated with bicuspid aortic valve remain unclear. NOTCH1 mutations are associated with bicuspid aortic valve and have been found in individuals with various left ventricular outflow tract abnormalities. Notch is a key signaling during cardiac valve formation that promotes the endothelial-to-mesenchymal transition. We address the role of Notch signaling in human aortic endothelial cells from patients with bicuspid aortic valve and aortic aneurysm. Aortic endothelial cells were isolated from tissue fragments of bicuspid aortic valve-associated thoracic aortic aneurysm patients and from healthy donors. Endothelial-to-mesenchymal transition was induced by activation of Notch signaling. Effectiveness of the transition was estimated by loss of endothelial and gain of mesenchymal markers by immunocytochemistry and qPCR. We show that aortic endothelial cells from the patients with aortic aneurysm and bicuspid aortic valve have down regulated Notch signaling and fail to activate Notch-dependent endothelial-to-mesenchymal transition in response to its stimulation by different Notch ligands. Our findings support the idea that bicuspid aortic valve and associated aortic aneurysm is associated with dysregulation of the entire Notch signaling pathway independently on the specific gene mutation. PMID- 26876947 TI - Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population. AB - BACKGROUND: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. METHODS: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. RESULTS: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 * 10(-9), odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 * 10(-8), OR = 10.7) and confirmed this association by comparing with an independent clozapine tolerant control group (n = 380, p = 2.97 * 10(-5), OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. CONCLUSIONS: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated. PMID- 26876949 TI - Corrigendum: Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study. PMID- 26876950 TI - Membrane topologies of the PGLa antimicrobial peptide and a transmembrane anchor sequence by Dynamic Nuclear Polarization/solid-state NMR spectroscopy. AB - Dynamic Nuclear Polarization (DNP) has been introduced to overcome the sensitivity limitations of nuclear magnetic resonance (NMR) spectroscopy also of supported lipid bilayers. When investigated by solid-state NMR techniques the approach typically involves doping the samples with biradicals and their investigation at cryo-temperatures. Here we investigated the effects of temperature and membrane hydration on the topology of amphipathic and hydrophobic membrane polypeptides. Although the antimicrobial PGLa peptide in dimyristoyl phospholipids is particularly sensitive to topological alterations, the DNP conditions represent well its membrane alignment also found in bacterial lipids at ambient temperature. With a novel membrane-anchored biradical and purpose built hardware a 17-fold enhancement in NMR signal intensity is obtained by DNP which is one of the best obtained for a truly static matrix-free system. Furthermore, a membrane anchor sequence encompassing 19 hydrophobic amino acid residues was investigated. Although at cryotemperatures the transmembrane domain adjusts it membrane tilt angle by about 10 degrees, the temperature dependence of two-dimensional separated field spectra show that freezing the motions can have beneficial effects for the structural analysis of this sequence. PMID- 26876951 TI - Probing the phenomenon of trained immunity in invertebrates during a transgenerational study, using brine shrimp Artemia as a model system. AB - The invertebrate's innate immune system was reported to show some form of adaptive features, termed trained immunity. However, the memory characteristics of innate immune system and the mechanisms behind such phenomena remain unclear. Using the invertebrate model Artemia, we verified the possibility or impossibility of trained immunity, examining the presence or absence of enduring memory against homologous and heterologous antigens (Vibrio spp.) during a transgenerational study. We also determined the mechanisms behind such phenomenon. Our results showed the occurrence of memory and partial discrimination in Artemia's immune system, as manifested by increased resistance, for three successive generations, of the progenies of Vibrio-exposed ancestors towards a homologous bacterial strain, rather than to a heterologous strain. This increased resistance phenotype was associated with elevated levels of hsp70 and hmgb1 signaling molecules and alteration in the expression of key innate immunity related genes. Our results also showed stochastic pattern in the acetylation and methylation levels of H4 and H3K4me3 histones, respectively, in the progenies whose ancestors were challenged. Overall results suggest that innate immune responses in invertebrates have the capacity to be trained, and epigenetic reprogramming of (selected) innate immune effectors is likely to have central place in the mechanisms leading to trained immunity. PMID- 26876952 TI - Behaviour of the Pleistocene marsupial lion deduced from claw marks in a southwestern Australian cave. AB - The marsupial lion, Thylacoleo carnifex, was the largest-ever marsupial carnivore, and is one of the most iconic extinct Australian vertebrates. With a highly-specialised dentition, powerful forelimbs and a robust build, its overall morphology is not approached by any other mammal. However, despite >150 years of attention, fundamental aspects of its biology remain unresolved. Here we analyse an assemblage of claw marks preserved on surfaces in a cave and deduce that they were generated by marsupial lions. The distribution and skewed size range of claw marks within the cave elucidate two key aspects of marsupial lion biology: they were excellent climbers and reared young in caves. Scrutiny of >10,000 co-located Pleistocene bones reveals few if any marsupial lion tooth marks, which dovetails with the morphology-based interpretation of the species as a flesh specialist. PMID- 26876953 TI - Transvesical laparoscopic surgery for double renal pelvis and ureter with or without ureterocele. AB - OBJECTIVE: To evaluate the performance of transvesical laparoscopic surgery for patients with complete double pelvis and ureter. METHODS: A total of 10 patients were included in the present study: five had complete double pelvis and ureter with ureterocele (group A), and five did not have ureterocele (group B). Three small incisions of 5 mm were used, without incision in the lower abdomen. In group A patients, the ureterocele wall was resected, and two ureters were sufficiently detached as a combined ureteral complex. Ureterocele on the side of the bladder wall was sutured to the bladder neck, and the bladder wall was strengthened. According to the cross-trigonal technique, ureterocystoneostomy was carried out in two ureters as a combined ureteral complex. In group B patients, two ureters were sufficiently detached, and ureterocystoneostomy was carried out as in group A. RESULTS: In group A, the mean age was 13.4 years (range 2-34 years). The mean operation time was 304.6 min (242-346 min). In group B, the mean age was 16.6 years (range 2-48 years). The mean operation time was 207.8 min (150 249 min). There were no intraoperative and postoperative complications in both study groups. CONCLUSIONS: Transvesical laparoscopic surgery can be safely and effectively used in patients with double pelvis and ureter. PMID- 26876954 TI - Bioluminescence Tomography-Guided Radiation Therapy for Preclinical Research. AB - PURPOSE: In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm. METHODS AND MATERIALS: The BLT system was designed to dock with the SARRP for image acquisition and to be detached before radiation delivery. A 3-mirror system was devised to reflect the bioluminescence emitted from the subject to a stationary charge-coupled device (CCD) camera. Multispectral BLT and the incomplete variables truncated conjugate gradient method with a permissible region shrinking strategy were used as the optimization scheme to reconstruct bioluminescent source distributions. To validate BLT targeting accuracy, a small cylindrical light source with high CBCT contrast was placed in a phantom and also in the abdomen of a mouse carcass. The center of mass (CoM) of the source was recovered from BLT and used to guide radiation delivery. The accuracy of the BLT-guided targeting was validated with films and compared with the CBCT-guided delivery. In vivo experiments were conducted to demonstrate BLT localization capability for various source geometries. RESULTS: Online BLT was able to recover the CoM of the embedded light source with an average accuracy of 1 mm compared to that with CBCT localization. Differences between BLT- and CBCT-guided irradiation shown on the films were consistent with the source localization revealed in the BLT and CBCT images. In vivo results demonstrated that our BLT system could potentially be applied for multiple targets and tumors. CONCLUSIONS: The online BLT/CBCT/SARRP system provides an effective solution for soft tissue targeting, particularly for small, nonpalpable, or orthotopic tumor models. PMID- 26876956 TI - Worldwide productivity in the hand and wrist literature: A bibliometric analysis of four highly cited subspecialty journals. AB - OBJECTIVE: Hand and wrist research has recently shown obvious progress. The quantity and quality of publications from different nations, however, have not been analyzed. In our study, we aimed to assess the characteristics of worldwide productivity in hand and wrist literature using highly cited subspecialty journals. METHODS: Literature search using the Web of Science database was conducted to identify hand and wrist articles in four highly cited subspecialty journals from 2005 to 2014. The number of articles, impact factors and citations were analyzed to evaluate the contributions of different countries. Publication activity was adjusted for the countries by population size. RESULTS: A total of 4268 publications were identified. The number of articles showed a significant increase of 2.10-fold between 2005 and 2014 (p = 0.0001). North America, West Europe, and East Asia were the most prolific areas. The majority of publications (92.03%) were from high-income countries, 7.97% from middle-income countries, and no publications from lower-income countries. The United States published the most articles (53.89%), followed by United Kingdom (6.51%), Japan (6.14%), Canada (3.70%), and China (3.37%). Articles originating from the United States showed the greatest number of total 5-year impact factors (5y-IF) (4059.56) and total citations (17,998). When normalized to population size, United States ranked the first (7.16), followed by Sweden (6.53), and Netherlands (5.72). However, Netherlands (1.893) had the highest mean 5y-IF, followed by Germany (1.884) and Australia (1.883). Sweden had the highest average citations per article (11.38), followed by Germany (9.63), and Australia (9.08). CONCLUSIONS: The number of publications of hand and wrist research shows a significant increase during the past 10 years. The United States is the most productive country in hand and wrist literature. However, some European countries and Australia may have higher quality of articles according to mean 5y-IF and mean citations per article. PMID- 26876955 TI - Health-Related Quality of Life in Locally Advanced Cervical Cancer Patients After Definitive Chemoradiation Therapy Including Image Guided Adaptive Brachytherapy: An Analysis From the EMBRACE Study. AB - PURPOSE: This study analyzed functioning and symptom scores for longitudinal quality of life (QoL) from patients with locally advanced cervical cancer who underwent definitive chemoradiation therapy with image guided adaptive brachytherapy in the EMBRACE study. METHODS AND MATERIALS: In total, 744 patients at a median follow-up of 21 months were included. QoL was prospectively assessed using European Organization for Research and Treatment of Cancer Quality of Life core module 30 (EORTC QLQ-C30) and EORTC cervical cancer module 24 (CX24) questionnaires at baseline, then every 3 months during the first year, every 6 months in the second and third years, and finally yearly thereafter in patients with no evidence of disease. Outcomes were evaluated over time and compared to those from an age-matched female reference population. RESULTS: General QoL and emotional and social functioning were impaired at baseline but improved during the first 6 months after treatment, to reach a level comparable to that of the reference population, whereas cognitive functioning remained impaired. Both social and role functioning showed the lowest scores at baseline but which increased after treatment to reach a plateau at 6 months and then declined slightly at 3 and 4 years. The overall symptom experience was elevated at baseline and decreased to a level within the range of that of the reference population. Similarly, tumor-related symptoms (eg, pain, appetite loss, and constipation), which were present before treatment, decreased substantially at the first follow-up after treatment. Several treatment-related symptoms developed either immediately after and persisted over time (diarrhea, menopausal symptoms, peripheral neuropathy, and sexual functioning problems) or developed gradually after treatment (lymphedema and dyspnea). CONCLUSIONS: This longitudinal prospective QoL analysis showed that patients' general QoL and functioning were impaired before treatment compared to those of reference data. Several tumor related symptoms resolved after treatment, and functioning and general QoL returned to that of the level of the reference population, indicating a transient impact of diagnosis and treatment. However, several treatment-related symptoms and problems did develop and persist, either immediately or gradually after treatment. PMID- 26876957 TI - Adapting the IDEAL Framework and Recommendations for medical device evaluation: A modified Delphi survey. AB - INTRODUCTION: Current regulatory systems for medical device marketing approval lack adequate requirements for evidence of safety and efficacy. The Total Product Life Cycle (TPLC) concept, with clinical use and marketing expanding as evidence develops, has won support, but lacks a template to define evidence requirements at different stages. The IDEAL Framework & Recommendations, originally developed for new surgical procedures, might provide such a template, but may require modification. METHODS: We conducted a Delphi expert consensus exercise to determine how IDEAL might be modified to accommodate the needs of device regulation. 34 experts were invited to participate in 3 rounds of questioning, with feedback of the results of each round to participants before the next. RESULTS: 27 of 34 experts responded in at least one survey round. Experts agreed that, after appropriate modifications, IDEAL could form an evidence template for a TPLC-based regulatory system. Necessary modifications include a new Stage 0 should guide reporting of pre-clinical studies, expansion of registries to all stages, and omission of IDEAL stages 2 and 3 for "successor" devices under certain conditions. DISCUSSION: A standard approach to TPLC evaluation of medical devices does not currently exist. The IDEAL Framework, if modified appropriately, could fill such a void and improve the safety of new medical devices. PMID- 26876958 TI - HAL-RAR (Doppler guided haemorrhoid artery ligation with recto-anal repair) is a safe and effective procedure for haemorrhoids. Results of a prospective study after two-years follow-up. AB - PURPOSE: To analyse prospectively results of HAL-RAR technique by evaluating pain, perioperative complications and clinical outcome after two years followup. METHODS: A prospective study design including 30 consecutive patients with haemorrhoids grade III-IV treated from June 2012. After discharge, patients received a specific questionnaire to record postoperative pain, delayed complications, evolution/disappearance of the symptoms that led to the surgical intervention (bleeding, prolapse, itching, pain and soiling). A visual analog scale (VAS) was used to measure pain. Outpatient follow-up was carried out at 7 days, and 1, 6 and 12 months and annually thereafter. Pre, intra and postoperative data (including physical examination) had been recorded prospectively. RESULTS: The median operating time (range) was 40 (26-60) minutes. Average hospital stay (range) was 11 (3-25) hours. No postoperative complications were observed in 29 cases (96.6%). Median follow-up was 26 (12-36) months. All the patients attended the follow-up. Mean postoperative pain was VAS = 1.7 on the seventh day and it was practically non-existent (VAS = 0.7) 1 month after the procedure. 87.5% of patients confirmed complete relief of symptoms after 30 days and 93% of patients feel free of symptoms 6 months after the procedure. No patient has experienced late complications as dyschezia, urgency, soiling or faecal incontinence. After 24 months follow-up, recurrence of bleeding and prolapse was observed in only 1 patient; 93% of patients have considered results of HAL-RAR as very good or excellent. CONCLUSION: HAL-RAR is safe and almost painless technique and it has very good results in the control of haemorrhoidal symptoms. This procedure should be considered as an effective first treatment option for haemorrhoids. PMID- 26876959 TI - The New Calcium Imaging Trend (Front Cell Neurosci 2015;9:436). PMID- 26876960 TI - Polymer thick film technology for improved simultaneous dEEG/MRI recording: Safety and MRI data quality. AB - PURPOSE: To develop a 256-channel dense-array electroencephalography (dEEG) sensor net (the Ink-Net) using high-resistance polymer thick film (PTF) technology to improve safety and data quality during simultaneous dEEG/MRI. METHODS: Heating safety was assessed with temperature measurements in an anthropomorphic head phantom during a 30-min, induced-heating scan at 7T. MRI quality assessment used B1 field mapping and functional MRI (fMRI) retinotopic scans in three humans at 3T. Performance of the 256-channel PTF Ink-Net was compared with a 256-channel MR-conditional copper-wired electroencephalography (EEG) net and to scans with no sensor net. A visual evoked potential paradigm assessed EEG quality within and outside the 3T scanner. RESULTS: Phantom temperature measurements revealed nonsignificant heating (ISO 10974) in the presence of either EEG net. In human B1 field and fMRI scans, the Ink-Net showed greatly reduced cross-modal artifact and less signal degradation than the copper wired net, and comparable quality to MRI without sensor net. Cross-modal ballistocardiogram artifact in the EEG was comparable for both nets. CONCLUSION: High-resistance PTF technology can be effectively implemented in a 256-channel dEEG sensor net for MR conditional use at 7T and with significantly improved structural and fMRI data quality as assessed at 3T. Magn Reson Med 77:895-903, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26876961 TI - Effect of vitamin D level on the immunogenicity to hepatitis B vaccination in dialysis patients. AB - We undertook this study to assess the response of hepatitis B vaccination in dialysis patients and the effect of vitamin D level on the immunogenicity to hepatitis B vaccination. It was an observational study, which included 60 patients of end-stage renal disease on maintenance dialysis. Patients with anti HBs antibody positive at baseline were excluded. All received intramuscular recombinant hepatitis B vaccination at 0, 1, 2, and 6 months 20 MUg on each deltoid muscle bilateral. Anti-HBs antibody titers were measured at 4 and 7 months of vaccination and the titer >=10 mIU/mL was considered as "positive". Vitamin D levels were measured at baseline before starting the vaccination. The mean vitamin D level was 15.0 +/- 7.8 ng/mL. The vitamin D level <10 and <20 were 23.3% and 83.3%, respectively. The patients on hemodialysis had relatively higher vitamin D level than on peritoneal dialysis patients, i.e. 16.3 +/- 8.5 and 11.5 +/- 3.1 ng/mL, respectively (p = 0.03). Overall, 38 patients responded to the immunization (63.3%) and 11 patients were non-responders (36.7%) at 4 months. Difference of vitamin D level in responder (16.6 +/- 9.1 ng/mL) and non-responder (12.4 +/- 4.1 ng/mL) was not significant (p = 0.16). At 7 months (1 month after completion of vaccination) 61.9% were responders and 38.1% were non-responders. The vitamin D level in responders and non-responders were statistically not significant (p = 0.11). In responder, titer >=100 mIU/mL was seen in 30% at 4 months and in 42.9% at 7 months (p = 0.05). In the good and weak responders at 7 months, vitamin D levels were 21.5 +/- 10.8 and 10.1 +/- 3.7 ng/mL, respectively (p = 0.37). The association of vitamin D level and anti-HBs antibody titer were not significant (r = 0.03 and 95% CI was -0.43 to 0.48, p = 0.89) in those who responded. Most patients on dialysis were vitamin D deficient. Vitamin D levels did not differ between responding and non-responding dialysis patients. PMID- 26876962 TI - Longitudinal PBL in Undergraduate Medical Education Develops Lifelong-Learning Habits and Clinical Competencies in Social Aspects. PMID- 26876963 TI - Correction of the auditory phenotype in C57BL/6N mice via CRISPR/Cas9-mediated homology directed repair. AB - BACKGROUND: Nuclease-based technologies have been developed that enable targeting of specific DNA sequences directly in the zygote. These approaches provide an opportunity to modify the genomes of inbred mice, and allow the removal of strain specific mutations that confound phenotypic assessment. One such mutation is the Cdh23 (ahl) allele, present in several commonly used inbred mouse strains, which predisposes to age-related progressive hearing loss. RESULTS: We have used targeted CRISPR/Cas9-mediated homology directed repair (HDR) to correct the Cdh23 (ahl) allele directly in C57BL/6NTac zygotes. Employing offset-nicking Cas9 (D10A) nickase with paired RNA guides and a single-stranded oligonucleotide donor template we show that allele repair was successfully achieved. To investigate potential Cas9-mediated 'off-target' mutations in our corrected mouse, we undertook whole-genome sequencing and assessed the 'off-target' sites predicted for the guide RNAs (<=4 nucleotide mis-matches). No induced sequence changes were identified at any of these sites. Correction of the progressive hearing loss phenotype was demonstrated using auditory-evoked brainstem response testing of mice at 24 and 36 weeks of age, and rescue of the progressive loss of sensory hair cell stereocilia bundles was confirmed using scanning electron microscopy of dissected cochleae from 36-week-old mice. CONCLUSIONS: CRISPR/Cas9-mediated HDR has been successfully utilised to efficiently correct the Cdh23 (ahl) allele in C57BL/6NTac mice, and rescue the associated auditory phenotype. The corrected mice described in this report will allow age-related auditory phenotyping studies to be undertaken using C57BL/6NTac-derived models, such as those generated by the International Mouse Phenotyping Consortium (IMPC) programme. PMID- 26876964 TI - Women's views on autologous cell-based therapy for post-obstetric incontinence. AB - AIM: Fecal and urinary incontinence are devastating consequences of obstetric related perineal injury. The aim of the present study is to determine acceptability to parous women of autologous cell-based therapy for fecal and urinary incontinence that arises due to pelvic diaphragm tearing during vaginal childbirth. MATERIALS & METHODS: A multiple choice questionnaire survey was offered to 76 parous women at the Maternity Unit, University College Hospital, London, UK. Seventy completed questionnaires - response rate: 92%. RESULTS: In total, 84% of women indicated a willingness to accept autologous cell-based therapy for obstetric injury-induced incontinence rather than surgery. CONCLUSION: These observational data provide an indication of likely acceptance of autologous cell-based therapies for birth injury incontinence and will help with designing new therapeutic approaches. PMID- 26876965 TI - An integrated microfluidic chip for immunomagnetic detection and isolation of rare prostate cancer cells from blood. AB - The quantitative and qualitative analysis of circulating tumor cells (CTCs) has the potential to improve the clinical management of several cancers, including prostate cancer. As such, there is much interest in the isolation of CTCs from the peripheral blood of cancer patients. We report the design, fabrication, and proof-of-principle testing of an integrated permalloy-based microfluidic chip for immunomagnetic isolation of blood-borne prostate cancer cells using an antibody targeting prostate surface membrane antigen (PSMA). The preliminary results using spiked blood samples indicate that the proposed device is consistently capable of isolating prostate cancer cells with high sensitivity (up to 98 %) at clinically relevant low concentrations (down to 20 cells/mL) and an acceptable throughput (100 MUL/min). PMID- 26876966 TI - Mean Platelet Volume, a Novel Biomarker in Adolescents with Severe Primary Dysmenorrhea. AB - STUDY OBJECTIVE: To evaluate whether mean platelet volume (MPV) would be a profitable marker in predicting disease severity in adolescents with severe primary dysmenorrhea (PD). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A total of 67 patients diagnosed with PD and 37 healthy adolescents with regular menstrual cycles were included in the study. Hemoglobin, MPV, and white blood cell, platelet, lymphocyte, and neutrophil counts were measured as part of the automated complete blood examination. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were obtained from the absolute neutrophil or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale was used to assess the level of pain, as mild (<40 mm), moderate (40-60 mm) and severe (>60 mm) PD. RESULTS: The MPV level of the combined severity of PD and control groups were similar. However, the MPV was significantly lower in the severe PD group compared with the control group (P = .04). There were no significant differences in the other hematological parameters between the groups. The mean visual analog scale score of the PD and control subjects were 7.35 +/- 2.25 and 1.07 +/- 1.96, respectively (P < .01). There was a poor negative correlation, which was statistically insignificant, between MPV and white blood cell count. CONCLUSION: The present study showed that MPV is decreased in adolescents with severe PD. Further studies with larger numbers of subjects are necessary to clarify the roles of platelets in the pathogenesis of severe PD and evaluate the changes in MPV value in response to treatment. PMID- 26876967 TI - Heavy Menstrual Bleeding as a Common Presenting Symptom of Rare Platelet Disorders: Illustrative Case Examples. AB - Heavy menstrual bleeding (HMB) is a common symptom in patients who present to the obstetrician-gynecologist or adolescent medicine specialist and might result from an underlying inherited bleeding disorder. Whereas relatively common bleeding disorders such as von Willebrand disease are often included in standard laboratory assessments, rarer platelet function disorders can be challenging to diagnose. Additionally, HMB can be a particularly difficult symptom to manage in adolescents with platelet function disorders, and it is associated with decreased quality of life. We review the diagnostic and management issues of patients with platelet function disorders through the presentation of 2 patient case reports, with a focus on a diagnosis of Glanzmann thrombasthenia, an inherited qualitative disorder that affects platelet function. Whereas the first patient presented to the emergency department before the diagnosis of a bleeding disorder and required a hematologic referral and extensive laboratory assessments, the second patient had been diagnosed with Glanzmann thrombasthenia as a child but experienced severe management challenges at the onset of menarche. In both patients, collaboration between the obstetrician-gynecologist or adolescent medicine specialist and the hematologist was critical for achieving acute management of the bleeding symptoms and for ensuring optimal long-term disease management. Together, these cases highlight the importance of properly identifying females with HMB who might have an undiagnosed bleeding disorder and of consulting with a hematologist to determine an appropriate management plan throughout all life stages. PMID- 26876968 TI - Spontaneous Reformation of Imperforate Hymen after Repeated Hymenectomy. AB - BACKGROUND: Imperforate hymen prevents menstrual blood drainage, which causes cyclic lower abdominal pain and amenorrhea. Untreated patients might develop serious complications such as endometriosis and infertility. Hymenectomy represents the adequate treatment. CASE: In a 16-year-old female virgin presented with recurrent lower abdominal pain, urine retention, and secondary amenorrhea after 3 hymenectomy surgeries. The examination revealed imperforate hymen. A fourth hymenectomy was performed with continuous locked sutures over all of the edges. SUMMARY AND CONCLUSION: Recurrent imperforate hymen after hymenectomy should be suspected if symptoms recur. Diagnosis can be achieved through meticulous clinical examination and appropriate imaging techniques. PMID- 26876969 TI - Inadvertent Intrathecal Injection during Percutaneous Epidural Neuroplasty Triggering Takotsubo Syndrome: What could be the Mechanism? PMID- 26876970 TI - Addition of an Enzymatic Hydrolysate of Bovine Globulins to Bread and Determination of Hypotensive Effects in Spontaneously Hypertensive Rats. AB - The aim of this study was to develop bread containing a papain hydrolysate of bovine alpha- and beta-globulins (GPH) with in vitro and in vivo antihypertensive activities. The physical characteristics of the formulated bread were assessed over a six day period and results suggested that the overall quality and acceptance of bread was not affected by the inclusion of GPH at a concentration of 4% (w/w). Bright field light microscopy and confocal scanning laser microscopy images were used to visualize the main ingredients of the bread. In addition, the antihypertensive activity of the bread was assessed in spontaneously hypertensive rats (SHRs) over a 24 h period where a maximum significant decrease in systolic blood pressure of 36.2 +/- 1.9 mmHg was observed 8 h after oral administration. Results demonstrate that the antihypertensive activity of GPH was resistant to the baking process and shows potential for use as a functional antihypertensive ingredient. PMID- 26876971 TI - Community Sewage Sensors towards Evaluation of Drug Use Trends: Detection of Cocaine in Wastewater with DNA-Directed Immobilization Aptamer Sensors. AB - Illicit drug use has a global concern and effective monitoring and interventions are highly required to combat drug abuse. Wastewater-based epidemiology (WBE) is an innovative and cost-effective approach to evaluate community-wide drug use trends, compared to traditional population surveys. Here we report for the first time, a novel quantitative community sewage sensor (namely DNA-directed immobilization of aptamer sensors, DDIAS) for rapid and cost-effective estimation of cocaine use trends via WBE. Thiolated single-stranded DNA (ssDNA) probe was hybridized with aptamer ssDNA in solution, followed by co-immobilization with 6 mercapto-hexane onto the gold electrodes to control the surface density to effectively bind with cocaine. DDIAS was optimized to detect cocaine at as low as 10 nM with a dynamic range from 10 nM to 5 MUM, which were further employed for the quantification of cocaine in wastewater samples collected from a wastewater treatment plant in seven consecutive days. The concentration pattern of the sampling week is comparable with that from mass spectrometry. Our results demonstrate that the developed DDIAS can be used as community sewage sensors for rapid and cost-effective evaluation of drug use trends, and potentially implemented as a powerful tool for on-site and real-time monitoring of wastewater by un-skilled personnel. PMID- 26876972 TI - The presence of extra chromosomes leads to genomic instability. AB - Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using a series of human cells with defined aneuploid karyotypes, that gain of a single chromosome increases genomic instability. Next-generation sequencing and SNP-array analysis reveal accumulation of chromosomal rearrangements in aneuploids, with break point junction patterns suggestive of replication defects. Trisomic and tetrasomic cells also show increased DNA damage and sensitivity to replication stress. Strikingly, we find that aneuploidy-induced genomic instability can be explained by the reduced expression of the replicative helicase MCM2-7. Accordingly, restoring near-wild-type levels of chromatin-bound MCM helicase partly rescues the genomic instability phenotypes. Thus, gain of chromosomes triggers replication stress, thereby promoting genomic instability and possibly contributing to tumorigenesis. PMID- 26876973 TI - Early Nephrology Referral 6 Months Before Dialysis Initiation Can Reduce Early Death But Does Not Improve Long-Term Cardiovascular Outcome on Dialysis. AB - BACKGROUND: There is a paucity of studies on whether early referral (ER) to nephrologist could reduce cardiovascular mortality on dialysis, and the length of pre-dialysis nephrological care needed to reduce mortality on dialysis. METHODS AND RESULTS: A total of 604 consecutive patients who started dialysis between 2001 and 2009 in Senshu region, Osaka, Japan were analyzed. Non-linear associations between mortality and pre-dialysis duration of nephrological care were assessed using restricted cubic spline function, and predictors for death analyzed on Cox modeling. A total of 31.6%, 18.2%, 11.3% and 6.1% of patients had >12, 24, 36 and 48 months of pre-dialysis care, respectively. A total of 258 patients (42.7%) were categorized as ER (>=6 months pre-dialysis duration). During the follow-up period (median, 31.1 months), 218 patients died (cardiovascular, n=70; infection, n=69). Although patients with late referral (LR) had a proxy of inappropriate pre-dialysis care compared with the ER group, Cox multivariate analysis failed to show a favorable association between ER and cardiovascular outcome. In contrast, a deleterious effect of LR on overall survival was observed but was limited only to the first 12 months of dialysis (HR, 1.957; 95% CI: 1.104-3.469; P=0.021), but not observed thereafter. CONCLUSIONS: Current pre-dialysis nephrological care may reduce short-term mortality but may not improve cardiovascular mortality after dialysis initiation. PMID- 26876974 TI - Cytomegalovirus-based vaccine expressing Ebola virus glycoprotein protects nonhuman primates from Ebola virus infection. AB - Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity. PMID- 26876975 TI - Effects of Chronic Stress on Alcohol Reward- and Anxiety-Related Behavior in High and Low-Alcohol Preferring Mice. AB - BACKGROUND: Stress exposure (SE) during adolescence is associated with an increased risk for the development of alcohol use disorders (AUDs). Past research has shown that SE during adolescence increases voluntary alcohol consumption in mice during adulthood; however, little is known about the positive or negative motivational aspects of this relationship. METHODS: High-alcohol preferring (HAP2) and low-alcohol preferring (LAP2) male mice were exposed to stress during adolescence, stress during adulthood, or no stress. After a 30-day interim, subjects were exposed to alcohol-induced place and footshock-induced fear conditioning procedures to measure stress-induced behavioral alterations during adulthood. RESULTS: SE during adolescence did not increase the magnitude of alcohol-induced conditioned place preference (CPP), as hypothesized, but increased the magnitude of conditioned fear, as measured by fear-potentiated startle (FPS), in HAP2 subjects only. Regardless of stress treatment group, LAP2 subjects showed greater alcohol-induced CPP expression than HAP2 mice. HAP2 mice also showed greater FPS than LAP2 mice, as previously shown. CONCLUSIONS: These results in mice, taken together with past research, suggest that mice exposed to stress during adolescence do not increase alcohol consumption during adulthood because of a greater sensitivity to the rewarding effects of alcohol, as measured via place conditioning. These results in mice also suggest that humans exposed to stress during adolescence may be more susceptible to developing anxiety during adulthood. The findings may be particularly relevant for humans with a familial history of AUDs. PMID- 26876976 TI - Exposure to psychosocial risks at work in prisons: does contact with inmates matter? A pilot study among prison workers in Spain. AB - Research has lately increased its focus on work conditions as predictors of stress among prison workers but only few studies have focused on how the exposure of workers to psychosocial risks vary according to their occupational groups and their contact with inmates. Work psychosocial risks (demands, control and social support) were assessed using the Spanish version of the Copenhagen Psychosocial Questionnaire among 164 Spanish prison workers (43 per cent of those surveyed). Regression analysis was used to explore how psychosocial hazards and their combinations (outcome variables) vary according to occupational groups. Results suggest that psychosocial risks were highest among guards that have more contact with inmates. Implications of the findings for policy making and practice application are discussed. PMID- 26876978 TI - World Health Organization Global AIDS Statistics. PMID- 26876979 TI - "Nanofiltration" Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples. AB - Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation. PMID- 26876980 TI - Emergence of influenza A (H1N1)pdm09 genogroup 6B and drug resistant virus, India, January to May 2015. AB - To investigate the aetiology of the 2015 A(H1N1)pdm09 influenza outbreak in India, 1,083 nasopharyngeal swabs from suspect patients were screened for influenza A(H1N1)pdm09 in the state of Madhya Pradesh. Of 412 positive specimens, six were further characterised by phylogenetic analysis of haemagglutinin (HA) sequences revealing that they belonged to genogroup 6B. A new mutation (E164G) was observed in HA2 of two sequences. Neuraminidase genes in two of 12 isolates from fatal cases on prior oseltamivir treatment harboured the H275Y mutation. PMID- 26876981 TI - Role of endoscopic surgery in the management of sinonasal and skull base schwannomas. AB - BACKGROUND: The purpose of this study was to report our experience with the endoscopic management of sinonasal schwannomas, analyzing the advantages, limitations, and outcomes of the technique. METHODS: A retrospective analysis was carried out on 11 patients treated endoscopically between 2000 and 2014 at a single institution. RESULTS: Eight patients underwent an exclusive endoscopic endonasal approach, whereas, in 3 patients, an osteoplastic flap was combined because of massive or lateral frontal sinus involvement. The tumor extended into the orbit in 5 cases, and involved the skull base in 5 patients who required a concomitant endoscopic duraplasty. No evidence of disease was observed in 10 patients after a mean follow-up of 90.1 months (range, 14-189 months). One patient was alive with persistence of disease, although asymptomatic. CONCLUSION: The endoscopic endonasal approach is a valid alternative for the vast majority of sinonasal schwannomas with minimal morbidity for the patient. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2074-E2082, 2016. PMID- 26876982 TI - ChemProt-3.0: a global chemical biology diseases mapping. AB - ChemProt is a publicly available compilation of chemical-protein-disease annotation resources that enables the study of systems pharmacology for a small molecule across multiple layers of complexity from molecular to clinical levels. In this third version, ChemProt has been updated to more than 1.7 million compounds with 7.8 million bioactivity measurements for 19,504 proteins. Here, we report the implementation of global pharmacological heatmap, supporting a user friendly navigation of chemogenomics space. This facilitates the visualization and selection of chemicals that share similar structural properties. In addition, the user has the possibility to search by compound, target, pathway, disease and clinical effect. Genetic variations associated to target proteins were integrated, making it possible to plan pharmacogenetic studies and to suggest human response variability to drug. Finally, Quantitative Structure-Activity Relationship models for 850 proteins having sufficient data were implemented, enabling secondary pharmacological profiling predictions from molecular structure. Database URL: http://potentia.cbs.dtu.dk/ChemProt/. PMID- 26876983 TI - Regulators of Androgen Action Resource: a one-stop shop for the comprehensive study of androgen receptor action. AB - Androgen receptor (AR) is a ligand-activated transcription factor that is the main target for treatment of non-organ-confined prostate cancer (CaP). Failure of life-prolonging AR-targeting androgen deprivation therapy is due to flexibility in steroidogenic pathways that control intracrine androgen levels and variability in the AR transcriptional output. Androgen biosynthesis enzymes, androgen transporters and AR-associated coregulators are attractive novel CaP treatment targets. These proteins, however, are characterized by multiple transcript variants and isoforms, are subject to genomic alterations, and are differentially expressed among CaPs. Determining their therapeutic potential requires evaluation of extensive, diverse datasets that are dispersed over multiple databases, websites and literature reports. Mining and integrating these datasets are cumbersome, time-consuming tasks and provide only snapshots of relevant information. To overcome this impediment to effective, efficient study of AR and potential drug targets, we developed the Regulators of Androgen Action Resource (RAAR), a non-redundant, curated and user-friendly searchable web interface. RAAR centralizes information on gene function, clinical relevance, and resources for 55 genes that encode proteins involved in biosynthesis, metabolism and transport of androgens and for 274 AR-associated coregulator genes. Data in RAAR are organized in two levels: (i) Information pertaining to production of androgens is contained in a 'pre-receptor level' database, and coregulator gene information is provided in a 'post-receptor level' database, and (ii) an 'other resources' database contains links to additional databases that are complementary to and useful to pursue further the information provided in RAAR. For each of its 329 entries, RAAR provides access to more than 20 well-curated publicly available databases, and thus, access to thousands of data points. Hyperlinks provide direct access to gene-specific entries in the respective database(s). RAAR is a novel, freely available resource that provides fast, reliable and easy access to integrated information that is needed to develop alternative CaP therapies. Database URL: http://www.lerner.ccf.org/cancerbio/heemers/RAAR/search/. PMID- 26876984 TI - Association between DCHS2 gene and mild cognitive impairment and Alzheimer's disease in an elderly Brazilian sample. AB - OBJECTIVES: In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. METHODS: 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE epsilon4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE epsilon4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE epsilon4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE epsilon4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE epsilon4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright (c) 2016 John Wiley & Sons, Ltd. CONCLUSIONS: Our findings suggest a possible role for DCHS2 gene in aMCI and AD. PMID- 26876985 TI - Aluminum alkyl complexes: synthesis, structure, and application in ROP of cyclic esters. AB - Aluminum alkyl complexes have very useful applications as catalysts or reagents in small molecule transformations and as cocatalysts in olefin polymerization. This short review focuses on some recent developments in the design, synthesis and structure of aluminum(iii) alkyl complexes supported by various ligands bearing nitrogen, oxygen, sulfur or phosphorus atoms, and their catalytic applications in the ring-opening polymerization (ROP) of cyclic esters. The coordination chemistry of the Al metal centre and the catalytic activity changes of the complexes caused by ligand modifications are also discussed. PMID- 26876986 TI - Prognostic factors in children with PRES and hematologic diseases. AB - OBJECTIVES: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological entity characterized by focal neurological signs, headache, confusion, and seizure, associated with transitory lesions in the posterior areas of the brain detectable with neuroimaging. Among children, one of the most common causes of PRES is cancer. MATERIALS AND METHODS: In this review, we present the cases of 5 children developing PRES after stem cell transplantation for hematological disease and review all the cases reported in English literature to investigate outcomes and associated risk factors. RESULTS: One hundred and eleven cases were reported. Hypertension was very frequent (80%). Clinical features included seizures (80.1%), headache (44.1%), visual disturbance (26.1%), and mental change (48.6%). EEG was abnormal in 27 of 32 patients. MRI revealed characteristic lesions in all patients even in early stages. Abnormal MRI findings in late stages were associated with neurological sequelae. Nineteen patients died (17.1%) of which 2 of PRES. Among alive patients, 17 had neurological sequelae. Four cases of PRES relapse were described. CONCLUSIONS: Thus, all transplant recipients with symptoms consistent with PRES should be promptly recognized to avoid long-term complications or even death. PMID- 26876987 TI - Predicting manual arm strength: A direct comparison between artificial neural network and multiple regression approaches. AB - In ergonomics, strength prediction has typically been accomplished using linked segment biomechanical models, and independent estimates of strength about each axis of the wrist, elbow and shoulder joints. It has recently been shown that multiple regression approaches, using the simple task-relevant inputs of hand location and force direction, may be a better method for predicting manual arm strength (MAS) capabilities. Artificial neural networks (ANNs) also serve as a powerful data fitting approach, but their application to occupational biomechanics and ergonomics is limited. Therefore, the purpose of this study was to perform a direct comparison between ANN and regression models, by evaluating their ability to predict MAS with identical sets of development and validation MAS data. Multi-directional MAS data were obtained from 95 healthy female participants at 36 hand locations within the reach envelope. ANN and regression models were developed using a random, but identical, sample of 85% of the MAS data (n=456). The remaining 15% of the data (n=80) were used to validate the two approaches. When compared to the development data, the ANN predictions had a much higher explained variance (90.2% vs. 66.5%) and much lower RMSD (9.3N vs. 17.2N), vs. the regression model. The ANN also performed better with the independent validation data (r(2)=78.6%, RMSD=15.1) compared to the regression approach (r(2)=65.3%, RMSD=18.6N). These results suggest that ANNs provide a more accurate and robust alternative to regression approaches, and should be considered more often in biomechanics and ergonomics evaluations. PMID- 26876988 TI - Representation of economic preferences in the structure and function of the amygdala and prefrontal cortex. AB - Social value orientations (SVOs) are economic preferences for the distribution of resources - prosocial individuals are more cooperative and egalitarian than are proselfs. Despite the social and economic implications of SVOs, no systematic studies have examined their neural correlates. We investigated the amygdala and dorsolateral prefrontal cortex (DLPFC) structures and functions in prosocials and proselfs by functional magnetic resonance imaging and evaluated cooperative behavior in the Prisoner's Dilemma game. We found for the first time that amygdala volume was larger in prosocials and positively correlated with cooperation, while DLPFC volume was larger in proselfs and negatively correlated with cooperation. Proselfs' decisions were marked by strong DLPFC and weak amygdala activity, and prosocials' decisions were marked by strong amygdala activity, with the DLPFC signal increasing only in defection. Our findings suggest that proselfs' decisions are controlled by DLPFC-mediated deliberative processes, while prosocials' decisions are initially guided by automatic amygdala processes. PMID- 26876989 TI - Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes. AB - Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all childhood ALL cases are due to such germline mutations, but the figure may be higher. Most of these syndromes are primarily characterized by their non-malignant phenotype, whereas ALL may be the dominating or even only striking manifestation of the syndrome in some families. Identification of such ALL patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring cancer predisposing mutations can be challenging for both the physician and the patient due to their preexisting symptoms, their reduced tolerance to radio- and/or chemotherapy with enhanced risk of life-threatening organ toxicities, and the paucity of data from ALL patients with the same or similar syndromes being treated by contemporary protocols. Recent studies clearly indicate that many of these patients stand a good chance of cure, and that they should be offered chemotherapy with the intention to cure. Some of these syndromes are characterized by reduced tolerance to radiotherapy and/or specific anticancer agents, while others are not. This review summarises our current knowledge on the risk of acute toxicities for these ALL patients and provides guidance for treatment adjustments. PMID- 26876990 TI - Integrated chemical and multi-scale structural analyses for the processes of acid pretreatment and enzymatic hydrolysis of corn stover. AB - Corn stover was pretreated with acid under moderate conditions (1.5%, w/w, 121 degrees C, 60min), and kinetic enzymolysis experiments were performed on the pretreated substrate using a mixture of Celluclast 1.5L (20FPU/g dry substrate) and Novozyme 188 (40CBU/g dry substrate). Integrated chemical and multi-scale structural methods were then used to characterize both processes. Chemical analysis showed that acid pretreatment removed considerable hemicellulose (from 19.7% in native substrate to 9.28% in acid-pretreated substrate) and achieved a reasonably high conversion efficiency (58.63% of glucose yield) in the subsequent enzymatic hydrolysis. Multi-scale structural analysis indicated that acid pretreatment caused structural changes via cleaving acetyl linkages, solubilizing hemicellulose, relocating cell wall surfaces and enlarging substrate porosity (pore volume increased from 0.0067cm(3)/g in native substrate to 0.019cm(3)/g in acid-pretreated substrate), thereby improving the polysaccharide digestibility. PMID- 26876991 TI - Exopolysaccharides of Lactobacillus reuteri: Their influence on adherence of E. coli to epithelial cells and inflammatory response. AB - The aim of the study was to characterize exopolysaccharides (EPS) originated from Lactobacillus reuteri strain DSM 17938 (EPS-DSM17938) and L. reuteri strain L26 BiocenolTM (EPS-L26) and evaluate their influence on adherence of enterotoxigenic Escherichia coli (ETEC) to IPEC-1 cells and proinflammatory gene expression. Both EPS were d-glucan polysaccharides with higher molecular weight (Mw), but differing in spatial conformation and elicited variable cytokine profile. EPS DSM17938, relatively linear polysaccharide with (1->4) and (1->6) glycosidic linkages, increased IL-1beta gene expression (0.1mg/mL; P<0.05), while EPS-L26, more branched polysaccharide with (1->3) and (1->6) glycosidic linkages, exerted slight but statistically significant up-regulation of NF-kappaB, TNF-alpha and IL 6 mRNA (P<0.05). The most significant finding is that preincubation of IPEC-1 cells with both EPS followed by ETEC infection inhibit ETEC adhesion on IPEC-1 cells (P<0.01) and ETEC-induced gene expression of proinflammatory cytokine IL 1beta and IL-6 (P<0.01). PMID- 26876992 TI - Extraction of cellulose from agricultural waste using Montmorillonite K-10/LiOH and its conversion to renewable energy: Biofuel by using Myrothecium gramineum. AB - Cellulose was extracted from agricultural waste like Rice Husk (RH) a renewable resource of India as well as in the World. Cellulose was isolated from rice husk (RH) using eco-friendly method with Montmorillonite K-10/LiOH solution and bleaching with 2% H2O2. The reaction parameters like time, temperature, catalyst, acid and alkali were studied to evaluate the optimum reaction conditions 6h, 80 degrees C, 20% maleic acid and 10% LiOH (in H2O) for time, temperature, acid and alkali, respectively. Renewable energy, biofuel from agricultural waste using Myrothecium gramineum was also investigated herein. Cellulose was converted to glucose by using acid hydrolysis and the optimum reaction conditions were 140 degrees C for 60min. in presence of H2SO4 (5% v/v). It has been recognized significantly as potential sustainable sources of sugars for fermentation to bioethanol. So, our effort was given to obtain bioethanol from RH using new and novel renewable fungal strain M. gramineum. M. gramineum was isolated from acacia plant available in NE region of India. The results revealed that % yields of cellulose, glucose and bioethanol were 68%, 60% and 25%, respectively. Moreover, the bioethanol was compared with the standard ethanol (Laboratory grade) and also the ethanol produced from the known microb Aspergillus niger. The synthesized products were characterized with the help of analytical techniques like FT-IR, GC, TGA, DSC and XRD. PMID- 26876993 TI - New antimicrobial chitosan derivatives for wound dressing applications. AB - Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have been designed to develop new wound dressing biomaterials. The structural, morphological and physico-chemical properties of synthesized chitosan derivatives were analyzed by FT-IR, (1)H NMR spectroscopy, scanning electron microscopy, swelling ability and porosity. Antimicrobial, in vivo testing and biodegradation behavior have been also performed. The chitosan derivative membranes showed improved swelling and biodegradation rate, which are important characteristics required for the wound healing process. The antimicrobial assay evidenced that chitosan-based sulfadiazine, sulfadimethoxine and sulfamethoxazole derivatives were the most active. The MTT assay showed that some of chitosan derivatives are nontoxic. Furthermore, the in vivo study on burn wound model induced in Wistar rats demonstrated an improved healing effect and enhanced epithelialization of chitosan-sulfonamide derivatives compared to neat chitosan. The obtained results strongly recommend the use of some of the newly developed chitosan derivatives as antimicrobial wound dressing biomaterials. PMID- 26876994 TI - Chitosan-phenylalanine-mPEG nanoparticles: From a single step water-based conjugation to the potential allergen delivery system. AB - The chemical modification to obtain biocompatible chitosan (CS) nanoparticles for the application in biological system is still on expectation. By simply mixing CS with hydroxybenzotriazole (HOBt), the CS aqueous solution obtained allows a successful single step conjugation of both hydrophobic biomolecules, i.e. phenylalanine (Phe), and hydrophilic polymers, i.e. poly(ethylene glycol) methyl ether (mPEG), on CS, in water at room temperature. The CS-Phe-mPEG nanoparticles (20-50nm) exhibit positive charge leading to an entrapment of negatively charged house dust mite allergen (HDM) extract (Dermatophagoides pteronyssinus). The HDM entrapped CS-Phe-mPEG shows biocompatibility as evidenced from the cell viability, the ROS (reactive oxygen species) reduction, and the HaCaTs proliferation. The clinical implementation on the healthy- and HDM-allergic volunteers indicates that the HDM-entrapped CS-Phe-mPEG stimulates cell-mediated immune response in peripheral blood mononuclear cells (PBMCs) and favors T cell immune response as seen from the reduction of interferon-(IFN)-gamma and interleukin-(IL)-10 in the PBMCs of the HDM-allergic volunteers. PMID- 26876995 TI - Characterization and antioxidant activities of extracellular and intracellular polysaccharides from Fomitopsis pinicola. AB - Fomitopsis pinicola (F. pinicola) is a kind of medicinal fungi, and few studies has been carried out on F. pinicola polysaccharides from liquid submerged cultivation. The characterization and antioxidant activities of extracellular polysaccharide (EPS) and intracellular polysaccharide (IPS) isolated from F. pinicola were investigated. The results showed that the molecular weight of EPS was 2.30*10(4)Da, and EPS was composed of mannose, rhamnose, xylose and galactose with the molar ratio of 0.1:1.0:0.3:0.5. The molecular weight of IPS was 4.07*10(5)Da, and the monosaccharide compositions included glucose, mannose, rhamnose, xylose and galactose with the molar ratio of 1.0:0.9:0.9:0.8:1.1. Antioxidant activities of both EPS and IPS including in vitro scavenging activities on 1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals, cellular protective effects on yeast cells from ultraviolet (UV) radiation and H2O2 oxidative damage were tested. Both EPS and IPS showed antioxidant activities in a dose dependent manner, and IPS had higher antioxidant activity than EPS. So EPS and IPS could be potential novel antioxidants for functional food. PMID- 26876996 TI - Starch composites with aconitic acid. AB - The aim of this project is to examine the effectiveness of using aconitic acid (AcA), a tricarboxylic acid which contains a carbon/carbon double bond (CC), to enhance the properties of starch-based films. Starch/glycerol cast films were prepared with 0, 2, 5, 10 and 15wt% AcA (starch wt% basis) and the properties analysed. It was shown that AcA acted as both a cross-linking agent and also a strong plasticising agent. The 5wt% AcA derived starch films were the most effectively cross-linked having the lowest solubility (28wt%) and decreased swelling coefficient (35vol.%) by approximately 3 times and 2.4 times respectively compared to the control film submerged in water (23 degrees C). There was also a significant increase in the film elongation at break by approximately 35 times (compared to the control) with the addition of 15wt% AcA, emphasising the plasticising effect of AcA. However, generally there was a reduced tensile strength, softening of the film, and reduced thermal stability with increased amounts of AcA. PMID- 26876997 TI - The interactions between cationic cellulose and Gemini surfactant in aqueous solution. AB - Due to the extensive application of cationic cellulose in cosmetic, drug delivery and gene therapy, combining the improvement effect of surfactant-cellulose complexes, to investigate the properties of cellulose in aqueous solution is an important topic from both scientific and technical views. In this study, the phase behavior, solution properties and microstructure of Gemini surfactant sodium 5-nonyl-2-(4-(4-nonyl-2-sulfonatophenoxy)butoxy)phenyl sulfite (9-4 9)/cationic cellulose (JR400, the ammonium groups are directly bonded to the hydroxyethyl substituent with a degree substitution of 0.37) mixture was investigated using turbidity, fluorescence spectrophotometer and shear rheology techniques. As a control, the interaction of corresponding monovalent surfactant, sodium 2-ethoxy-5-nonylbenzenesulfonate (9-2) with JR400 in aqueous solution was also studied. Experimental results showed that 9-4-9/JR400 mixture has lower critical aggregation concentration (CAC) and critical micelle concentration (CMC) (about one order of magnitude) than 9-2/JR400 mixture. A low concentration of Gemini surfactant 9-4-9 appeared to induce an obvious micropolarity and viscosity value variation of the mixture, while these effects required a high concentration of corresponding monovalent one. Furthermore, dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements illuminated the formation and collapse procedure of network structure of the 9-4-9/JR400 mixture, which resulted in the increase and decrease of viscosity. These results suggest that the molecular structure of the surfactant has a great effect on its interaction with cationic cellulose. Moreover, the Gemini surfactant/cationic cellulose mixture may be used as a potencial stimuli-responsive drug delivery vector which not only load hydrophilic drugs, but also deliver hydrophobic substances. PMID- 26876998 TI - Effect of nanoclay on the properties of low density polyethylene/linear low density polyethylene/thermoplastic starch blend films. AB - The aim of this work is to study effect of nanoclay (Cloisite((r))15A) on morphology and properties of low-density polyethylene/linear low-density polyethylene/thermoplastic starch (LDPE/LLDPE/TPS) blend films. LDPE/LLDPE blend (70/30wt/wt) containing 15wt.% TPS in the presence of PE-grafted maleic anhydride (PE-g-MA, 3wt.%) with 1, 3 and 5phr of nanoclay are compounded in a twin-screw extruder and then film blown using a blowing machine. Nanocomposites with intercalated structures are obtained, based on the X-ray diffraction (XRD) and transmission electron microscopy (TEM) studies. However, some exfoliated single platelets in the samples are also observable. Scanning electron microscopic (SEM) images confirm the ability of both exfoliated nanoclay and PE-g-MA to reduce the size of TPS domains and deform their particles within the PE matrices. As the nanoclay content increases from 1 to 5phr, the tensile strength, tear resistance and impact strength of the films increase, whereas a slight decrease in the elongation at break is observed. The film samples with 5phr nanoclay possess the required packaging properties, as specified by ASTM D4635. These films provide desired optical transparency and surface roughness which are more attractive for packaging applications. PMID- 26876999 TI - Development of biomimetic nanocomposites as bone extracellular matrix for human osteoblastic cells. AB - Here, we have developed biomimetic nanocomposites containing chitosan, poly(vinyl alcohol) and nano-hydroxyapatite-zinc oxide as bone extracellular matrix for human osteoblastic cells and characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction. Scanning electron microscopy images revealed interconnected macroporous structures. Moreover, in this study, the problem related to fabricating a porous composite with good mechanical strength has been resolved by incorporating 5wt% of nano-hydroxyapatite-zinc oxide into chitosan-poly(vinyl alcohol) matrix; the present composite showed high tensile strength (20.25MPa) while maintaining appreciable porosity (65.25%). These values are similar to human cancellous bone. These nanocomposites also showed superior water uptake, antimicrobial and biodegradable properties than the previously reported results. Compatibility with human blood and pH was observed, indicating nontoxicity of these materials to the human body. Moreover, proliferation of osteoblastic MG-63 cells onto the nanocomposites was also observed without having any negative effect. PMID- 26877000 TI - PEGylation of 6-amino-6-deoxy-curdlan for efficient in vivo siRNA delivery. AB - RNA interference (RNAi) is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies need to establish efficient delivery system that silences target genes with siRNA doses that is clinically feasible in humans. Here we report synthesis and in vivo study of a novel PEGylated curdlan-based nanoparticle, designated as 6AC-100PEG, obtained by conjugation of mPEG 2000 to 6-amino-6-deoxy-curdlan. The complex of siRNA/6AC 100PEG showed homogenous nanoparticles with an average diameter of 200nm. MTT assay indicated that 6AC-100PEG does not have apparent cytotoxicity. Systemic administration of a complex of siapoB/6AC-100PEG significantly reduced the level of apoB mRNA in mouse liver, indicating that 6AC-100PEG can efficiently deliver siRNA to mouse liver and induce RNAi. Administration of siRNA/6AC-100PEG to mouse did not elevate liver enzyme level in the serum, indicating that 6AC-100PEG nanoparticle is a promising in vivo siRNA delivery agent. PMID- 26877001 TI - Conformation study of E-cyclodextrin: Replica exchange molecular dynamics simulations. AB - There is growing interest in large-ring cyclodextrins (LR-CDs) which are known to be good host molecules for larger ligands. The isolation of a defined size LR-CD is an essential prerequisite for studying their structural properties. Unfortunately the purification procedure of these substances turned out to be very laborious. Finally the problem could be circumvented by a theoretical consideration: the highly advantageous replica exchange molecular dynamics (REMD) simulation (particularly suitable for studies of conformational changes) offers an ideal approach for studying the conformational change of E-cyclodextrin (CD10), a smaller representative of LR-CDs. Three carbohydrate force fields and three solvent models were tested. The conformational behavior of CD10 was analyzed in terms of the flip (turn) of the glucose subunits within the macrocyclic ring. In addition a ranking of conformations with various numbers of turns was preformed. Our findings might be also helpful in the temperature controlled synthesis of LR-CDs as well as other experimental conditions, in particular for the host-guest reaction. PMID- 26877002 TI - Morphological characteristics, oxidative stability and enzymic hydrolysis of amylose-fatty acid complexes. AB - Complexes of amylose with fatty acids varying in carbon chain length and degree of unsaturation were prepared at 30, 50 or 70 degrees C by dissolving amylose in 0.1N KOH and mixing with fatty acid potassium soap solution. The complexes were obtained in solid form as precipitates after neutralization. SEM microscopy revealed that the morphology of the complexes was that of ordered lamellae separated from amorphous regions whereas confocal laser scanning microscopy showed images of the topography of the guest molecules in the complex matrix. FTIR spectroscopy revealed that the absorption peak attributed to carbonyl group of free fatty acid was shifted when the fatty acid was in the form of amylose complex. Thermo-gravimetry showed that the unsaturated fatty acids were effectively protected from oxidation when they were complexed with amylose whereas enzymic hydrolysis experiments showed that the guest molecules were quantitatively released from the amylose complexes. PMID- 26877003 TI - Nano-photo active cellulosic fabric through in situ phytosynthesis of star-like Ag/ZnO nanocomposites: Investigation and optimization of attributes associated with photocatalytic activity. AB - In this study, nano-photo active cellulosic fabric was prepared through in situ phytosynthesis of star-like Ag/ZnO nanocomposites using the ashes of Seidlitzia rosmarinus plants so-called Keliab. This is provided alkali media as a vital condition for synthesis of nanocomposites, further increasing the reduce-ability of cellulosic chains by activation of hydroxyl groups. The intermolecular dehydrolysis of intermediates ions under thermal and alkaline conditions leads to formation of Ag/ZnO heterostructure. Various analytical techniques were employed to confirm Ag/ZnO nanocomposites on the cotton fabric. The surface morphology, crystal phase and chemical structure of the treated fabrics were characterized by field emission and scanning electron microscopy (FE-SEM and SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDX). Moreover, influence of precursors: silver nitrate, zinc acetate and Keliab solution on attributes associated with photocatalytic activities including self-cleaning, whiteness and wettability was investigated via central composite design (CCD). The treated cotton samples exhibited self-cleaning activities through methylene blue degradation under day-light exposure along with improved wettability and whiteness. The prepared sample in optimized conditions showed good antibacterial activities against Staphylococcus aureus and Escherichia coli with enhanced fabric tensile strength. PMID- 26877004 TI - Thixotropic properties of waxy potato starch depending on the degree of the granules pasting. AB - This paper presents the rheological instability (thixotropy/antithixotropy) of waxy potato starch (WPS) pastes depending on their concentration (1-5% w/w) and pasting temperature (80, 95 and autoclaved: 121 degrees C, at 0.1MPa). The hysteresis loop, apparent viscosity at constant shear rate as well as the in shear structural recovery tests with and without pre-shearing were applied. The pastes were also characterized by the granularity profile, molecular weight, polydispersity and optical transmittance. Differences in rheological properties of the pastes prepared at 80 and 95 degrees C as well as autoclaved resulted from degree of granules pasting. At 121 degrees C dissolution of the granules occurred, while at the lower temperatures only the partial pasting of the granules took place. Pasting temperature of WPS significantly influenced rheological parameters of the resulted pastes which had thixotropic, antithixotropic or mixed thixotropic/antithixotropic behavior. Autoclaved pastes, regardless their concentration were antithixotropic as demonstrated by the areas of hysteresis loops derived from the flow curves signalized by the degree of structure recovery (DSR) which exceeded unity. The apparent viscosity of WPS pasted at 121 degrees C strongly decreased as compared to the samples pasted at lower temperatures. Samples pasted at 80 and 95 degrees C showed both thixotropic and antithixotropic behavior, with a predominance of the latter. The starch concentration played an important role in the formation of the rheological properties of the resulted pastes. Its influence was strongly connected with the degree of the granules pasting, therefore with the temperature of pastes preparation. For the pastes prepared at 80 and 95 degrees C the values of thixotropy and apparent viscosity increased, while the values of DSR decreased with an increase of concentration. In the autoclaved pastes the antithixotropy, DSR and apparent viscosity increased with increasing starch concentration. It was also found that apart from the concentration and temperature also the shear rate influence the thixotropic behavior. PMID- 26877005 TI - Study on oil absorbency of succinic anhydride modified banana cellulose in ionic liquid. AB - Banana cellulose contained number of hydrophilic hydroxyl groups which were succinylated to be hydrophobic groups with high oil affinity. Succinic anhydride was used to modify banana cellulose in 1-allyl-3-methylimidazolium chloride ionic liquid in this study. The modified banana cellulose had a high oil absorption capacity. The effects of reaction time, temperature, and molar ratio of succinic anhydride to anhydroglucose on the degree of substitution of modified banana cellulose were evaluated. The optimal reaction condition was at a ratio of succinic anhydride and anhydroglucose 6:1 (m:m), reaction time 60min and temperature 90 degrees C. The maximum degree of acylation reaction reached to 0.37. The characterization analysis of the modified banana cellulose was performed using X-ray diffractometer, Fourier transform infrared spectrometer, scanning electron microscopy and thermogravimetry. The oil absorption capacity and kinetics of the modified banana cellulose were evaluated at the modified cellulose dose (0.025-0.3g), initial oil amount (5-30g), and temperature (15-35 degrees C) conditions. The maximum oil absorption capacity was 32.12g/g at the condition of the cellulose dose (0.05g), initial oil amount (25g) and temperature (15 degrees C). The kinetics of oil absorption of the cellulose followed a pseudo second-order model. The results of this study demonstrated that the modified banana cellulose could be used as an efficient bio-sorbent for oil adsorption. PMID- 26877006 TI - In situ development of self-reinforced cellulose nanocrystals based thermoplastic elastomers by atom transfer radical polymerization. AB - Recently, the utilization of cellulose nanocrystals (CNCs) as a reinforcing material has received a great attention due to its high elastic modulus. In this article, a novel strategy for the synthesis of self-reinforced CNCs based thermoplastic elastomers (CTPEs) is presented. CNCs were first surface functionalized with an initiator for surface-initiated atom transfer radical polymerization (SI-ATRP). Subsequently, SI-ATRP of methyl methacrylate (MMA) and butyl acrylate (BA) was carried out in the presence of sacrificial initiator to form CTPEs in situ. The CTPEs together with the simple blends of CNCs and linear poly(MMA-co-BA) copolymer (P(MMA-co-BA)) were characterized for comparative study. The results indicated that P(MMA-co-BA) was successfully grafted onto the surface of CNCs and the compatibility between CNCs and the polymer matrix in CTPEs was greatly enhanced. Specially, the CTPEs containing 2.15wt% CNCs increased Tg by 19.2 degrees C and tensile strength by 100% as compared to the linear P(MMA-co-BA). PMID- 26877007 TI - Preparation and characterization of resistant starch type IV nanoparticles through ultrasonication and miniemulsion cross-linking. AB - This study aimed to assess the properties of resistant starch type IV (chemically modified starch, RS4) prepared from a new and convenient synthesis route by using ultrasonication combined with water-in-oil miniemulsion cross-linking technique. A three-factor Box-Behnken design and optimization was used to minimize particle size through the developed RS4 nanoparticles. The predicted minimized Z-Avel (576.1nm) under the optimum conditions of the process variables (ultrasonic power, 214.57W; sonication time, 114.73min; and oil/water ratio, 10.54:1) was very close to the experimental value (651.0nm) determined in a batch experiment. After preparing the RS4 nanoparticles, morphological, physical, chemical, and functional properties were assessed. Results revealed that RS4 nanoparticle size reached about 600nm. Scanning electron microscopy images showed that ultrasonication induced notches and grooves on the surface. Under polarized light, the polarized cross was impaired. X-ray diffraction results revealed that the crystalline structure was disrupted. Smaller or no endotherms were exhibited in DSC analysis. In the FTIR graph, new peaks at 1532.91 and 1451.50cm(-1) were observed, and pasting properties were reduced. Amylose content, solubility, and SP increased, but RS content decreased. Anti-digestibility remained after ultrasonication. The prepared RS4 nanoparticles could be extensively used in biomedical applications and in the development of new medical materials. PMID- 26877009 TI - Purification of cress seed (Lepidium sativum) gum: Physicochemical characterization and functional properties. AB - The aim of the present study was to investigate the effects of different purification methods (ethanol, isopropanol and ethanol-isopropanol) on the physicochemical and functional characteristics of cress seed gum. Sugar composition and molecular weight of the samples varied significantly. All the purification methods reduced ash and protein content and molecular weight of cress seed gum. The main decomposition of the purified samples started above 200 degrees C and initial decomposition temperature of the crude gum was 190.21 degrees C. DSC thermograms of the purified gums showed two exothermic events at 257.81-261.95 degrees C and 302.46-311.57 degrees C. Crude gum displayed an exothermic peak at 259.42 degrees C. Sample I (purified using isopropanol) imparted the best surface activity among the purified samples as it had the highest protein and uronic acid contents and the lowest Mw. All the purification methods could improve emulsifying properties of cress seed gum and there was no significant difference among the purified samples. Crude gum showed the lowest foaming properties, while samples I and E (purified using ethanol) showed the highest foaming capacity and foam stability, respectively. PMID- 26877008 TI - Culture of low density E. coli cells in alginate-chitosan microcapsules facilitates stress resistance by up-regulating luxS/AI-2 system. AB - Entrapped low density cells with culture (ELDCwc) have been proved as a more effective way than direct entrapped high density cells (dEHDC) and free cells to protect probiotics from harsh environment, that is, to improve their stress resistance. The aim of this study was to investigate whether bacterial quorum sensing (QS) facilitated the stress resistance of Escherichia coli in microcapsules by detecting the expression of luxS/AI-2 system. As a result, both the expression of luxS gene and the concentration of autoinducer-2 (AI-2, QS signal molecule) have been discovered higher in ELDCwc than in dEHDC and free cells. Besides that, the luxS mutant E. coli strain was used as a negative control of QS to verify the influence of QS on bacterial stress resistance in microcapsules. The significantly decreased viability of luxS mutant strain in simulated gastric fluid also indicated that the QS played a critical role in protecting microorganisms from severe environment. PMID- 26877010 TI - Preparation and characterization of crosslinked chitosan/gelatin scaffolds by ice segregation induced self-assembly. AB - Chitosan and gelatin are biodegradable and biocompatible polymers which may be used in the preparation of 3D scaffolds with applications in biomedicine. Chitosan/gelatin scaffolds crosslinked with glutaraldehyde were prepared by ice segregation induced self-assembly (ISISA); a unidirectional freezing at -196 degrees C followed freeze-drying to produce macroporous materials with a well patterned structure. This process may be included within the green chemistry by the preparation of the porous structures without using organic solvents, moreover is a versatile, non-difficult and cheap process. The scaffolds prepared by ISISA were characterized by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, thermal gravimetric analysis, differential scanning calorimetry, and their stability was evaluated by degree swelling and degradation tests. The scaffolds present properties as high porosity, high degree swelling and good stability which make them suitable of applications as biomaterials. PMID- 26877011 TI - Rapid determination of gamma-value and xanthate group distribution on viscose by liquid-state (1)H NMR spectroscopy. AB - A method for the determination of the gamma-value and more importantly the distribution of xanthate groups on cellulose xanthate produced during the viscose process is presented. The method is based upon stabilization of xanthate groups attached to the cellulose chain by reaction with 4-methylbenzyl bromide and analysis of the resulting product by liquid-state (1)H NMR. Careful analysis of the proton-spectrum using deconvolution gave a very fast method for the measurement of the gamma-value which compared well with the data obtained by IR spectroscopy. In addition it could be shown that the distribution of the xanthate groups on the anhydroglucose monomeric unit (xanthation at position 2, 3 or 6) changes significantly during ripening. The method gave useful results even for viscose with low gamma-values of about 25. PMID- 26877012 TI - The immune adjuvant response of polysaccharides from Atractylodis macrocephalae Koidz in chickens vaccinated against Newcastle disease (ND). AB - Build on our previous research, polysaccharides from the rhizome of Atractylodis macrocephalae Koidz (RAMPS), RAMPStp and RAMPS60c were prepared and the structural characterization and immune response of ND vaccine in chicken were investigated. Immune organ index, Lymphocyte proliferation, antibody titers, cell cycle distribution, and percentages of CD4(+) and CD8(+) cells were determined. GPC analysis showed that the Mn of RAMPS with two peaks were 1.29*10(5) and 1.74*10(3), respectively. GC-MS analysis revealed that RAMPS was composed of glucose, mannose, arabinose, galactose, xylose, d-Ribose and rhamnose, with mass percentages of 66.39%, 21.24%, 5.64%, 2.65%, 2.30%, 1.15% and 0.64%, respectively. NMR spectroscopic analysis demonstrated that a preliminary structure of RAMPS was proposed as 1,3-linked beta-d-Galp and 1,6-linked beta-d Galpresidues. In vivo test showed that RAMPStp and RAMPS60c could promote peripheral lymphocytes proliferation and entering into S and G2/M phases, enhance serum HI antibody titer and effectively improve the percentages of CD4(+) and CD8(+) T cells in chickens vaccinated with ND vaccine at most time points. The actions of RAMPStp and RAMPS60c were stronger than that of Lev, and RAMPStp presented the best efficacy. These results indicated that RAMPStp and RAMPS60c characterize of the immune-enhancing activity and RAMPStp possessed the strongest activity. It would be anticipated as a component of new-type immunopotentiator. PMID- 26877013 TI - Development of a rapid method for simultaneous separation of hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparin by capillary electrophoresis. AB - This study reports the use of diethylenetriamine as background electrolyte for the simultaneous separation of hyaluronan acid, chondroitin sulfate, dermatan sulfate and heparin. The analytes were baseline separated by using an uncoated fused silica capillary at 37 degrees C with a run time of 23min. The migration order, with hyaluronan acid at first and heparin at last, was related to the sulfation degree. The effect of salt concentration on resolution and migration order was also investigated. The developed method was applied to the simultaneous determination of hyaluronan acid and chondroitin sulfate in mouse plasma. Interferences in plasma were removed by protein precipitation and glycosaminoglycans were further purified by ethanol precipitation. The method was validated over the concentration range from 50 to 600MUg/mL for hyaluronan acid and 500 to 6000MUg/mL for chondroitin sulfate in mouse plasma. Results from assay validations showed that the method was selective and robust. PMID- 26877014 TI - Characterization and toxicology evaluation of chitosan nanoparticles on the embryonic development of zebrafish, Danio rerio. AB - In the present study, chitosan nanoparticles were prepared, characterized and used to evaluate the embryonic toxicology on zebrafish (Danio rerio). The average particle size of chitosan nanoparticles was 84.86nm. The increased mortality and decreased hatching rate was found in the zebrafish embryo exposure to normal chitosan particles and chitosan nanoparticles with the increased addition concentration. At 120h post-fertilization (hpf), the rate of mortality were 25.0 and 44.4% in the groups treated with chitosan nanoparticles and normal chitosan particles at 250mg/L, respectively. At 72hpf, the hatching rate in the groups treated with normal chitosan particles were lower (P<0.01) at 300 and 400mg/L than those of the corresponding control groups, respectively. However, there were no significant differences between the groups treated with chitosan nanoparticles and the control groups across all the addition concentrations. More abundant typical malformation of embryos was observed in the groups treated with normal chitosan particles compared with those treated with chitosan nanoparticles. The LC50 (medium lethal concentration) of chitosan nanoparticles was 280mg/L at 96hpf and 270mg/L at 120hpf. As for normal chitosan particles, the LC50 was 257mg/L at both 96hpf and 120hpf. The TC50 (medium teratogenic concentration) of the zebrafish treated with chitosan nanoparticles and normal chitosan particles were 257mg/L and 137mg/L, respectively. It indicated that the chitosan nanoparticles were relatively more secure compared with normal chitosan particles. PMID- 26877015 TI - Crystalline structure and morphological properties of porous cellulose/clay composites: The effect of water and ethanol as coagulants. AB - In this study, cellulose foams incorporated with surface-modified montmorillonite (SM-MMT) were prepared following NaOH dissolution and regeneration into water and ethanol. According to the SEM images, the type of coagulating agent significantly affected the morphological properties of composite foams. The crystalline parameters were evaluated using wide-angle X-ray diffraction (WAXD), which showed an increase in crystal size as the effect of SM-MMT; however, the crystal size decreased for the samples treated with ethanol. The distribution of hydrogen bond types was also investigated using Fourier transform infrared (FTIR). Resolving the hydrogen-bonded OH stretching band at around 3340 into five bands indicated that presence of SM-MMT caused the shift of OH-stretching vibration band to lower wave number due to new hydrogen bonds between cellulose and SM-MMT. In general, the results indicated a change in the contents of the intra- and inter-molecular hydrogen bonds when the coagulant was changed or SM-MMT was incorporated. PMID- 26877016 TI - Structure and antinociceptive effects of beta-D-glucans from Cookeina tricholoma. AB - Structurally different water-insoluble (1->3),(1->6) beta-D-glucans were isolated from aqueous and alkaline extracts of the mushroom-forming ascomycete Cookeina tricholoma, a wild edible mushroom found in Brazilian Amazon forest. The structures showed different substitution patterns, which may influence their extractability and consequently their conformation in solution, and different MW (4.3*10(5)Da, 3.7*10(5)Da and 8.2*10(5)Da, for ICW-Ct, IHW-Ct and IK2-Ct, respectively). The main-chains are composed of (1->3)-linked beta-D-Glcp units O 6 substituted by side chains with different lengths of (1->6)-linked beta-d-Glcp units (ICW-Ct and IHW-Ct) or by a combination of (1->6)-linked beta-D-Glcp units and single units of beta-D-Glcp (IK2-Ct). beta-D-glucans with similar MW and showing only (1->6)-linked beta-D-Glcp units as side chains (ICW-Ct and IHW-Ct) showed significant inhibition of neurogenic pain, 69+/-11 and 57+/-11% at the dose of 10mgkg(-1), respectively, in the model of nociception induced by intraplantar injection of formalin. PMID- 26877017 TI - Controlled growth of Cu2O nanoparticles bound to cotton fibres. AB - A green, safe and fast procedure is presented for in situ generation of nanoparticles (NPs) of cuprous oxide (Cu2O) onto cotton fibres at room temperature using water as a solvent. The method is based on a mild surface oxidation of cellulose fibres to generate in a controlled way carboxylic groups acting as a binding site for the adsorption of Cu(2+) via electrostatic coordination. Then, the adsorbed Cu(2+) ions were readly converted into Cu2O by dipping the treated cotton fibres into a aqueous solution of a reducing agent. Field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD), as well as UV-vis absorption and emission spectroscopic methods were used to analyse the size, morphology, chemical composition and the crystalline structure of the generated nanoparticles on the fabrics. The morphology of the ensuing Cu2O nanoparticles was shown to be dependent on the reduycing agent used. Antibacterial properties of the modified fibres were also investigated. PMID- 26877018 TI - Hemicellulose isolation, characterization, and the production of xylo oligosaccharides from the wastewater of a viscose fiber mill. AB - Viscose fiber mills generate a lot of wastewater enriched with hemicelluloses. The structure of the hemicellulose in the wastewater was characterized and the hemicellulose was isolated to produce xylo-oligosaccharides (XOS). It was confirmed that the hemicellulose was mainly 4-O-methylglucuronoxylan with a small amount of glucomannan and xyloglucan. The 4-O-methylglucuronoxylan was completely de-acetylated and linear with a few 4-O-methyl glucuronic acid attached. After purified by the acid precipitation and washing, the hemicellulose was pretreated by dilute acid, and then subjected to xylanase hydrolysis. After the dilute H2SO4 pretreatment at pH 2.6 and 150 degrees C for 30min and the followed xylanase hydrolysis (65IU/g xylan), the total XOS yield was improved from 0.215 to 0.578g/g xylan. The percentage of XOS in the final sugar product was 68.9%. These results demonstrated the potential economical and environmental benefits of the process to utilize the byproducts from viscose fiber mills. PMID- 26877019 TI - Reaction efficiency and retention of poly(styrene-co-maleimide) nanoparticles deposited on fibrillated cellulose surfaces. AB - Surface modification of micro- and nanofibrillated cellulose (MFC and NFC) under aqueous environment was performed by deposition of poly(styrene-co-maleimide) nanoparticles synthesized by imidization of poly(styrene-co-maleic anhydride) in presence of wax and ammonium hydroxide in variable amounts. Specifically, the influences of fiber fibrillation on nanoparticle formation (i.e., reaction efficiency) and permanent nanoparticle deposition on the fiber surface (i.e., retention) were investigated. The surface modification was mainly governed by the fiber diameter, surface charges and amount of wax. As such, the MFC affected the imidization reaction to a smaller extent (i.e., high reaction efficiency) and was more densely deposited by nanoparticles than NFC (i.e., high retention). Moreover, wax protected the fibers against fibrillation and peeling-off at high temperature and favored nanoparticle deposition. As a result, water contact angles of 142 degrees were obtained for modified MFC in parallel with a surface coverage of 92%. PMID- 26877020 TI - Formation of type 4 resistant starch and maltodextrins from amylose and amylopectin upon dry heating: A model study. AB - Starch is one of the main components of human diet. During food processing, starch is submitted to high temperatures in the presence or absence of water. Thus, the main goal of this work was to identify structural modifications caused by dry heating in starch polysaccharides (amylose and amylopectin) and structurally related oligosaccharides, maltotetraose (M4) and glucosyl maltotriose (GM3), simulating processing conditions. The structural modifications were evaluated by methylation analysis, electrospray mass spectrometry (ESI-MS), tandem mass spectrometry (ESI-MS/MS) and anionic chromatography after in vitro enzymatic digestion. Dry heating promoted dehydration, depolymerization, as well as changes in Glc glycosidic linkage positions and anomeric configuration. In oligosaccharides, polymerization was also observed. All these changes resulted in a lower in vitro digestibility, suggesting that dry heating of starch polysaccharides and related oligosaccharides may be associated with the formation of type 4 resistant starch and maltodextrins, non-digestible carbohydrates that are responsible for beneficial effects in human intestinal tract. PMID- 26877021 TI - Enzyme-Dependent [4 + 2] Cycloaddition Depends on Lid-like Interaction of the N Terminal Sequence with the Catalytic Core in PyrI4. AB - The Diels-Alder [4 + 2] cycloaddition reaction is one of the most powerful and elegant organic synthesis methods for forming 6-membered molecules and has been known for nearly a century. However, whether and how enzymes catalyze this type of reaction is still not completely clear. Here we focus on PyrI4, an enzyme found in the biosynthetic pathway of pyrroindomycins where it catalyzes the formation of a spiro-conjugate via an enzyme-dependent exo-selective [4 + 2] cycloaddition reaction. We report the crystal structures of PyrI4 alone and in complex with its product. Comparative analysis of these structures, combined with biochemical analysis, lead us to propose a unique trapping mechanism whereby the lid-like action of the N-terminal tail imposes conformational constraints on the beta barrel catalytic core, which enhances the proximity and polarization effects of reactive groups (1,3-diene and alkene) to drive cyclization in a regio- and stereo-specific manner. This work represents an important step toward the wider application of enzyme-catalyzed [4 + 2] cyclization for synthetic purposes. PMID- 26877022 TI - Fluorescent RNA Aptamers as a Tool to Study RNA-Modifying Enzymes. AB - RNA-modifying enzymes are difficult to assay due to the absence of fluorometric substrates. Here we show that the Broccoli, a previously reported fluorescent RNA dye complex, can be modified to contain N(6)-methyladenosine, a prevalent mRNA base modification. Methylated Broccoli is nonfluorescent but, upon demethylation by the RNA demethylases fat mass and obesity-associated protein (FTO) or ALKBH5, it binds and activates the fluorescence of its cognate fluorophore. We describe a high-throughput screen (HTS) for FTO inhibitors using the fluorogenic methylated Broccoli substrate HTS assay, which performs robustly with a Z' factor >0.8 in the LOPAC1280 library. This allowed the identification of novel high-affinity FTO inhibitors. Several of these compounds were selective for FTO over the related demethylase, ALKBH5, and increase methylation of endogenous FTO target mRNAs in cells. Lastly, we show that Broccoli can be modified to contain other base modifications, suggesting that this approach could be generally applicable for assaying diverse RNA-modifying enzymes. PMID- 26877023 TI - Drug Repurposing Approach Identifies Inhibitors of the Prototypic Viral Transcription Factor IE2 that Block Human Cytomegalovirus Replication. AB - New targets for antiviral strategies are needed against human cytomegalovirus (HCMV), a major human pathogen. A cell-based screen aimed at finding inhibitors of the viral transcription factor Immediate-Early 2 (IE2) was performed in HCMV infected cells expressing EGFP under the control of an IE2-inducible viral promoter. Screening of a library of bioactive small molecules led to the identification of several compounds able to inhibit EGFP expression and also HCMV replication with potency in the low-micromolar range. Follow-up studies with four selected hits indicated that they all block viral DNA synthesis as well as viral Early and Late gene expression. Furthermore, mechanistic studies confirmed that the compounds specifically act via inhibition of IE2 transactivating activity, thus blocking viral Early gene expression and the progression of virus replication. These results provide proof of concept for identifying small molecules that modulate the activity of a microbial transcription factor to control pathogen replication. PMID- 26877025 TI - Nanoscale covalent organic frameworks as smart carriers for drug delivery. AB - Two porous covalent organic frameworks (COFs) with good biocompatibility were employed as drug nanocarriers, where three different drugs were loaded for subsequent drug release in vitro. The present work demonstrates that COFs are applicable in drug delivery for therapeutic applications. PMID- 26877024 TI - Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis. AB - Class I lantibiotic dehydratases dehydrate selected Ser/Thr residues of a precursor peptide. Recent studies demonstrated the requirement of glutamyl tRNA(Glu) for Ser/Thr activation by one of these enzymes (NisB) from the Firmicute Lactococcus lactis. However, the generality of glutamyl-tRNA(Glu) usage and the tRNA specificity of lantibiotic dehydratases have not been established. Here we report the 2.7-A resolution crystal structure, along with the glutamyl tRNA(Glu) utilization of MibB, a lantibiotic dehydratase from the Actinobacterium Microbispora sp. 107891 involved in the biosynthesis of the clinical candidate NAI-107. Biochemical assays revealed nucleotides A73 and U72 within the tRNA(Glu) acceptor stem to be important for MibB glutamyl-tRNA(Glu) usage. Using this knowledge, an expression system for the production of NAI-107 analogs in Escherichia coli was developed, overcoming the inability of MibB to utilize E. coli tRNA(Glu). Our work provides evidence for a common tRNA(Glu)-dependent dehydration mechanism, paving the way for the characterization of lantibiotics from various phyla. PMID- 26877026 TI - Overview of legislation on sewage sludge management in developed countries worldwide. AB - The need to apply innovative technologies for maximizing the efficiency and minimizing the carbon footprint of sewage treatment plants has upgraded sewage sludge management to a highly sophisticated research and development sector. Sewage sludge cannot be regarded solely as 'waste'; it is a renewable resource for energy and material recovery. From this perspective, legislation on sewage sludge management tends to incorporate issues related to environmental protection, public health, climate change impacts and socio-economic benefits. This paper reviews the existing legislative frameworks and policies on sewage sludge management in various countries, highlighting the common ground as well as the different priorities in all cases studied. More specifically, the key features of legislation regarding sludge management in developed countries such as the USA, Japan, Australia, New Zealand and the European Union (EU27) are discussed. PMID- 26877027 TI - The anaerobic baffled reactor (ABR) treating communal wastewater under mesophilic conditions: a review. AB - A review concerning the anaerobic baffled reactor (ABR) treating communal wastewater under mesophilic conditions is presented. Existing studies indicate strong resilience of the reactor towards loading variations and shock-loads. The compartmentalisation of the ABR is a strongly stabilising factor with feed fluctuations being evened out across reactor chambers. Significant chemical oxygen demand (COD) reduction occurs almost exclusively in the first three chambers. The hydraulic rather than the organic loading rate is treatment limiting. Laboratory-scale studies show high treatment efficiencies of above 80% COD removal. It was found that most laboratory-scale studies do not factor in important aspects of field operation, such as diurnal fluctuations of feed characteristics, adequate start-up periods and periods of constant loading and optimised chamber outlet design, and never studied the effect of loading on sludge digestion. Performance data on full-scale ABR implementations, however, are extremely scarce, and existing studies are without exception affected by site specific treatment-limiting factors hindering the extrapolation of generally valid conclusions. In view of a large-scale roll-out, communal ABRs are not sufficiently understood. Current challenges concerning the optimisation of reactor design require numerous well-monitored long-term full-scale reactor investigations. Existing ABR investigations yield encouraging results, supporting that the ABR may be one of the solutions answering the global call for low maintenance, robust treatment systems. PMID- 26877028 TI - Nitrogen removal from raw landfill leachate by an algae-bacteria consortium. AB - A remediation system for the removal of nitrogen from landfill leachate by a mixed algae-bacteria culture was investigated. This system was designed to treat leachate with minimal inputs and maintenance requirements, and was operated as an open semi-batch reactor in an urban greenhouse. The results of this study showed a maximum nitrogen removal rate of 9.18 mg N/(L.day) and maximum biomass density of 480 mg biomass/L. The ammonia removal rates of this culture increased with increasing initial ammonia concentration; maximum nitrogen removal occurred at an ammonia concentration of 80 mg N-NH3/L. At starting ammonia concentrations above 80 mg N-NH3/L a reduction in nitrogen removal was seen; this inhibition is hypothesized to be caused by ammonia toxicity. This inhibiting concentration is considerably higher than that of many other published studies. PMID- 26877029 TI - Preparation and photoelectrocatalytic performance of N-doped TiO2/NaY zeolite membrane composite electrode material. AB - A novel composite electrode material based on a N-doped TiO2-loaded NaY zeolite membrane (N-doped TiO2/NaY zeolite membrane) for photoelectrocatalysis was presented. X-ray diffraction (XRD), scanning electron microscopy (SEM), UV visible (UV-vis) and X-ray photoelectron spectroscopy (XPS) characterization techniques were used to analyze the structure of the N-doped TiO2/NaY zeolite membrane. The XRD and SEM results verified that the N-doped TiO2 nanoparticles with the size of ca. 20 nm have been successfully loaded on the porous stainless steel-supported NaY zeolite membrane. The UV-vis result showed that the N-doped TiO2/NaY zeolite membrane exhibited a more obvious red-shift than that of N-TiO2 nanoparticles. The XPS characterization revealed that the doping of N element into TiO2 was successfully achieved. The photoelectrocatalysis performance of the N-doped TiO2/NaY zeolite membrane composite electrode material was evaluated by phenol removal and also the effects of reaction conditions on the catalytic performance were investigated. Owing to exhibiting an excellent catalytic activity and good recycling stability, the N-doped TiO2/NaY zeolite membrane composite electrode material was of promising application for photoelectrocatalysis in wastewater treatment. PMID- 26877030 TI - Activation of persulfate/copper by hydroxylamine via accelerating the cupric/cuprous redox couple. AB - Cuprous copper [Cu(I)] reacts with sodium persulfate (PDS) to generate sulfate radical SO4(-)*, but it has been seldom investigated owing to its instability and difficulty in dissolving it. This study proposes a new method to regenerate Cu(I) from cupric copper [Cu(II)] by addition of hydroxylamine (HA) to induce the continuous production of radicals through active PDS, and investigates the resulting enhanced methyl orange (MO) degradation efficiency and mechanism in the new system. HA accelerated the degradation of MO markedly in the pH range from 6.0 to 8.0 in the HA/Cu(II)/PDS process. Both SO4(-)* and hydroxyl radicals (*OH) were considered as the primary reactive radicals in the process. The MO degradation in the HA/Cu(II)/PDS process can be divided into three stages: the fast stage, the transitory stage, and the low stage. MO degradation was enhanced with increased dosage of PDS. Although high dosage of HA could accelerate the transformation of the Cu(II)/Cu(I) cycle to produce more reactive radicals, excess HA can quench the reactive radicals. This study indicates that through a copper-redox cycling mechanism by HA, the production of SO4(-)* and *OH can be strongly enhanced, and the effective pH range can be expanded to neutral conditions. PMID- 26877031 TI - Hydrophobic aggregation of fine particles in high muddied coal slurry water. AB - The hydrophobic aggregation of fine particles in high muddied coal slurry water in the presence of four quaternary ammonium salts of 1231(dodecyl trimethyl ammonium chloride), 1431(tetradecyl trimethyl ammonium chloride), 1631(cetyl trimethyl ammonium chloride) and 1831(octadecyl trimethyl ammonium chloride) was investigated through the measurement of contact angles, zeta potentials, aggregation observation, adsorption and sedimentation. The results show that quaternary ammonium salts can enhance the hydrophobicity and reduce the electronegativity of particle surface, and thus induce a strong hydrophobic aggregation of slurry fine particles which promotes the settlement of coal slurry water. The adsorption of quaternary ammonium salts on slurry particles increases with the increase of alkyl chain length and reagent dosage, and will reach equilibrium when the dosage reaches a certain value. Weak alkaline conditions also can promote quaternary ammonium salts to be adsorbed on the coal slurry fine particles. In addition, reasonable energy input and a chemical environment of weak alkaline solution are conducive to hydrophobic aggregation settlement of high muddied coal slurry water with quaternary ammonium salts. The main mechanism of hydrophobic aggregation of coal slurry particles with quaternary ammonium salts is 'adsorption charge neutralization' and hydrophobic interaction. PMID- 26877032 TI - Pretreatment of concentrated leachate by the combination of coagulation and catalytic ozonation with Ce/AC catalyst. AB - A raw concentrated leachate produced from membrane bioreactor-nanofiltration (MBR NF) was taken from Chengdu Chang'an Waste Landfill Site, China. The major fraction of this concentrated leachate was large refractory humic substances. A coagulation-ozonation process was applied to treat this leachate, aiming at enhancing chemical oxygen demand (COD) removal efficiency and increasing its biodegradability. Meanwhile the molecular size distribution of the leachate, before and after coagulation and ozonation treatment, was analyzed by using ultrafiltration membrane separation. Coagulation pretreatment effectively removed varieties of large molecules in the raw concentrated leachate. The addition of Ce/AC greatly improved the oxidative ability of O3 in COD removal in the ozonation of coagulated leachate. The biochemical oxygen demand (BOD5)/COD ratio increased from 0.011 for the untreated concentrated leachate to 0.30 for the effluent of the coagulation-catalytic ozonation process, which indicated that a subsequent biological treatment could be readily conducted. The stability test demonstrated that the Ce/AC catalyst was effective and stable in the catalytic ozonation process. According to the results of molecular size distribution analysis, a direct correlation was observed between the increase of BOD5/COD and the decrease of apparent molecular weight. PMID- 26877033 TI - Seepage-zone recognition of river water based on Cl(-) spatial difference. AB - Based on Cl(-) monitoring data of river water and shallow groundwater samples on both sides of the Dashi River, we analyzed spatial distribution of Cl(-) content in surface water and groundwater, and evaluated the retardation strength, pCl(-), the average retardation strength, pA, and the average residual retardation strength, pAR, of surface-groundwater Cl(-) content. We introduce the difference, Q, of the average retardation strength and the average residual retardation strength, which can be used to identify the seepage zone and the transition seepage zone of the river, and to quantitatively express the seepage range. The results show that Cl(-) content in the river gradually increased in areas with industrial agglomeration, but decreased in areas with non-agglomeration, and gradually decreased along the river flow. If Q >= 0, then there is no seepage zone in the study area, but if Q < 0, then there is a seepage zone in the study area. The sampling point is in the seepage zone when pCl(-) <= pA, in the transition seepage zone when pA < pCl(-) <= pAR, and in the no-seepage zone when pCl(-) > pAR. The recognition results are more consistent with field investigation. PMID- 26877034 TI - Numerical simulation of wrinkle morphology formation and the evolution of different Bacillus subtilis biofilms. AB - Wrinkle morphology is a distinctive phenomenon observed in mature biofilms that are produced by a great number of bacteria. The wrinkle pattern depends on the mechanical properties of the agar substrate and the biofilm itself, governed by the extracellular matrix (ECM). Here we study the macroscopic structures and the evolution of Bacillus subtilis biofilm wrinkles using the commercial finite element software ABAQUS. A mechanical model and simulation are set up to analyze and evaluate bacteria biofilm's wrinkle characteristics. We uncover the wrinkle formation mechanism and enumerate the quantitative relationship between wrinkle structure and mechanical properties of biofilm and its substrate. Our work can be used to modify the wrinkle pattern and control the biofilm size. PMID- 26877035 TI - Exploration of rapid start-up of the CANON process from activated sludge inoculum in a sequencing biofilm batch reactor (SBBR). AB - In this study, a laboratory-scale sequencing biofilm batch reactor (SBBR) was employed to explore a fast start-up of completely autotrophic nitrogen removal over nitrite (CANON) process. Partial nitrification was achieved by controlling free ammonia concentration and operating at above 30 degrees C; then the reactor was immediately operated with alternating periods of aerobiosis and anaerobiosis to start the anammox process. The CANON process was successfully achieved in less than 50 d, and the total-nitrogen removal efficiency and the nitrogen removal rate were 81% and 0.14 kg-N m(-3) d(-1) respectively. Afterwards, with the increasing of ammonium loading rate a maximum nitrogen removal rate of 0.39 kg-N m(-3) d(-1) was achieved on day 94. DNA analysis showed that 'Candidatus Brocadia' was the dominant anammox species and Nitrosomonas was the dominant aerobic ammonium-oxidizing bacteria in the CANON reactor. This study revealed that due to shortening the persistent and stable nitrite accumulation period the long start-up time of the CANON process can be significantly reduced. PMID- 26877036 TI - A new and effective approach to boron removal by using novel boron-specific fungi isolated from boron mining wastewater. AB - Boron-resistant fungi were isolated from the wastewater of a boron mine in Turkey. Boron removal efficiencies of Penicillium crustosum and Rhodotorula mucilaginosa were detected in different media compositions. Minimal Salt Medium (MSM) and two different waste media containing molasses (WM-1) or whey + molasses (WM-2) were tested to make this process cost effective when scaled up. Both isolates achieved high boron removal yields at the highest boron concentrations tested in MSM and WM-1. The maximum boron removal yield by P. crustosum was 45.68% at 33.95 mg l(-1) initial boron concentration in MSM, and was 38.97% at 42.76 mg l(-1) boron for R. mucilaginosa, which seemed to offer an economically feasible method of removing boron from the effluents. PMID- 26877037 TI - Biogas production in an anaerobic sequencing batch reactor by using tequila vinasses: effect of pH and temperature. AB - In recent years, anaerobic digestion has been recognized as a suitable alternative for tequila vinasses treatment due to its high energy recovery and chemical oxygen demand (COD) removal efficiency. However, key factors such as the lack of suitable monitoring schemes and the presence of load disturbances, which may induce unstable operating conditions in continuous systems, have limited its application at full scale. Therefore, the aim of this work was to evaluate the anaerobic sequencing batch reactor (AnSBR) configuration in order to provide a low cost and easy operation alternative for the treatment of these complex effluents. In particular, the AnSBR was evaluated under different pH-temperature combinations: 7 and 32 degrees C; 7 and 38 degrees C; 8 and 32 degrees C and 8 and 38 degrees C. Results showed that the AnSBR configuration was able to achieve high COD removal efficiencies (around 85%) for all the tested conditions, while the highest methane yield was obtained at pH 7 and 38 degrees C (0.29 L/g COD added). Furthermore, high robustness was found in all the AnSBR experiments. Therefore, the full-scale application of the AnSBR technology for the treatment of tequila vinasses is quite encouraging, in particular for small and medium size tequila industries that operate under seasonal conditions. PMID- 26877038 TI - Thermodynamic modelling of a membrane distillation crystallisation process for the treatment of mining wastewater. AB - Membrane distillation (MD) could be applicable in zero liquid discharge applications. This is due to the fact that MD is applicable at high salinity ranges which are generally outside the scope of reverse osmosis (RO) applications, although this requires proper management of precipitating salts to avoid membrane fouling. One way of managing these salts is with MD crystallisation (MDC). This paper focuses on the applicability of MDC for the treatment of mining wastewater by thermodynamically modelling the aqueous chemistry of the process at different temperatures. The paper is based on the typical brine generated from an RO process in the South African coal mining industry and investigates the effect water recovery and operating temperature have on the salts that are predicted to crystallise out, the sequence in which they will crystallise out and purities as a function of the water recovery. The study confirmed the efficacy of using thermodynamic modelling as a tool for investigating and predicting the crystallisation aspects of the MDC process. The key finding from this work was that, for an MDC process, a purer product can be obtained at higher operating temperatures and recoveries because of the inverse solubility of calcium sulphate. PMID- 26877039 TI - Role of ammonia-oxidizing bacteria in micropollutant removal from wastewater with aerobic granular sludge. AB - Nitrifying wastewater treatment plants (WWTPs) are more efficient than non nitrifying WWTPs to remove several micropollutants such as pharmaceuticals and pesticides. This may be related to the activity of nitrifying organisms, such as ammonia-oxidizing bacteria (AOBs), which could possibly co-metabolically oxidize micropollutants with their ammonia monooxygenase (AMO). The role of AOBs in micropollutant removal was investigated with aerobic granular sludge (AGS), a promising technology for municipal WWTPs. Two identical laboratory-scale AGS sequencing batch reactors (AGS-SBRs) were operated with or without nitrification (inhibition of AMOs) to assess their potential for micropollutant removal. Of the 36 micropollutants studied at 1 MUg l(-1) in synthetic wastewater, nine were over 80% removed, but 17 were eliminated by less than 20%. Five substances (bisphenol A, naproxen, irgarol, terbutryn and iohexol) were removed better in the reactor with nitrification, probably due to co-oxidation catalysed by AMOs. However, for the removal of all other micropollutants, AOBs did not seem to play a significant role. Many compounds were better removed in aerobic condition, suggesting that aerobic heterotrophic organisms were involved in the degradation. As the AGS-SBRs did not favour the growth of such organisms, their potential for micropollutant removal appeared to be lower than that of conventional nitrifying WWTPs. PMID- 26877040 TI - An investigation into the potential use of nutrients recovered from urine diversion on a summer housing site: self-sufficiency based on nitrogen balance. AB - ECOSAN is a recent domestic wastewater management concept which suggests segregation at the source. One of these streams, yellow water (human urine) has the potential to be used as fertilizer, directly or indirectly, because of its rich content of plant nutrients. One physicochemical method for indirect use is adsorption/ion exchange using clinoptilolite. This paper aims to present the results of a scenario focusing on possible diversion of urine and self sufficiency of nutrients recovered on site through the use of this process, using actual demographic and territorial information from an existing summer housing site. Specifically, this paper aims to answer the questions: (i) how much nitrogen can be recovered to be used as fertilizer by diverting urine? and (ii) is this sufficient or in surplus within the model housing site? This sets an example of resource-oriented sanitation using stream segregation as a wastewater management strategy in a small community. Nitrogen was taken as the basis of calculations/predictions and the focus was placed on whether nitrogen is self sufficient or in excess as fertilizer for use within the premises. The results reveal that the proposed application makes sense and that urine coming from the housing site is self-sufficient as fertilizer within the housing site itself. PMID- 26877041 TI - Effect of different pH coking wastewater on adsorption of coking coal. AB - H2SO4 has an effect on the sorption of organic contaminants by coking coal (CC) in wastewater. This paper focused on the effect of pH on the removal of chemical oxygen demand (COD), phenols and ammonia. UV-vis spectra, Fourier transform infrared spectra, zeta potential and Brunauer, Emmett and Teller (BET) analysis were investigated to characterize the changes of CC properties and coking wastewater (CW) at different pH values. The results showed that the COD and phenol removal efficiencies increased with decreasing pH value, while the ammonia removal efficiency was decreased gradually. A new transmittance band in the region of 340-600 cm(-1) was observed in UV-vis spectra of CW in acidic condition. The absolute value of the zeta potential as the solution was gradually increasing with the increasing of pH value. Surface area and total pore volume of CC which was immersed in acidic solutions measured by BET were much higher than that of raw CC. CC has a greater adsorption capacity to organic pollution in the acidic solution mainly by van der Waals forces and hydrogen bonding. PMID- 26877042 TI - Examination of food waste co-digestion to manage the peak in energy demand at wastewater treatment plants. AB - Many digesters in Germany are not operated at full capacity; this offers the opportunity for co-digestion. Within this research the potentials and limits of a flexible and adapted sludge treatment are examined with a focus on the digestion process with added food waste as co-substrate. In parallel, energy data from a municipal wastewater treatment plant (WWTP) are analysed and lab-scale semi continuous and batch digestion tests are conducted. Within the digestion tests, the ratio of sewage sludge to co-substrate was varied. The final methane yields show the high potential of food waste: the higher the amount of food waste the higher the final yield. However, the conversion rates directly after charging demonstrate better results by charging 10% food waste instead of 20%. Finally, these results are merged with the energy data from the WWTP. As an illustration, the load required to cover base loads as well as peak loads for typical daily variations of the plant's energy demand are calculated. It was found that 735 m3 raw sludge and 73 m3 of a mixture of raw sludge and food waste is required to cover 100% of the base load and 95% of the peak load. PMID- 26877043 TI - Laboratory-scale membrane up-concentration and co-anaerobic digestion for energy recovery from sewage and kitchen waste. AB - This study assessed an alternative concept for co-treatment of sewage and organic kitchen waste in Vietnam. The goal was to apply direct membrane filtration for sewage treatment to generate a permeate that is suitable for discharge. The obtained chemical oxygen demand (COD) concentrations in the permeate of ultrafiltration tests were indeed under the limit value (50 mg/L) of the local municipal discharge standards. The COD of the concentrate was 5.4 times higher than that of the initial feed. These concentrated organics were then co-digested with organic kitchen wastes at an organic loading rate of 2.0 kg VS/m(3).d. The volumetric biogas production of the digester was 1.94 +/- 0.34 m(3)/m(3).d. The recovered carbon, in terms of methane gas, accounted for 50% of the total carbon input of the integrated system. Consequently, an electrical production of 64 Wh/capita/d can be obtained when applying the proposed technology with the current wastes generated in Ho Chi Minh City. Thus, it is an approach with great potential in terms of energy recovery and waste treatment. PMID- 26877044 TI - Wastewater treatment--adsorption of organic micropollutants on activated HTC carbon derived from sewage sludge. AB - Organic micropollutants (MPs), in particular xenobiotics and their transformation products, have been detected in the aquatic environment and the main sources of these MPs are wastewater treatment plants. Therefore, an additional cleaning step is necessary. The use of activated carbon (AC) is one approach to providing this additional cleaning. Industrial AC derived from different carbonaceous materials is predominantly produced in low-income countries by polluting processes. In contrast, AC derived from sewage sludge by hydrothermal carbonization (HTC) is a regional and sustainable alternative, based on waste material. Our experiments demonstrate that the HTC-AC from sewage sludge was able to remove most of the applied MPs. In fact more than 50% of sulfamethoxazole, diclofenac and bezafibrate were removed from artificial water samples. With the same approach carbamazepine was eliminated to nearly 70% and atrazine more than 80%. In addition a pre-treated (phosphorus-reduced) HTC-AC was able to eliminate 80% of carbamazepine and diclofenac. Atrazine, sulfamethoxazole and bezafibrate were removed to more than 90%. Experiments using real wastewater samples with high organic content (11.1 g m(-3)) succeeded in proving the adsorption capability of phosphorus-reduced HTC-AC. PMID- 26877045 TI - Investigation of equilibrium and kinetics of Cr(VI) adsorption by dried Bacillus cereus using response surface methodology. AB - In this study, response surface methodology (RSM) based on three-variable-five level central composite rotatable design was used to analyze the effects of combined and individual operating parameters (biomass dose, initial concentration of Cr(VI) and pH) on the Cr(VI) adsorption capacity of dried Bacillus cereus. A quadratic polynomial equation was obtained to predict the adsorbed Cr(VI) amount. Analysis of variance showed that the effect of biomass dose was the key factor in the removal of Cr(VI). The maximum adsorbed Cr(VI) amount (30.93 mg g(-1)) was found at 165.30 mg L(-1), 2.96, and 3.01 g L(-1) for initial Cr(VI) concentration, pH, and biosorbent dosage, respectively. The surface chemical functional groups and microstructure of unloaded and Cr(VI)-loaded dried Bacillus cereus were identified by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), respectively. Besides, the results gained from these studies indicated that Langmuir isotherm and the second-order rate expression were suitable for the removal of Cr(VI) from wastewater. The results revealed RSM was an effective method for optimizing biosorption process, and dried Bacillus cereus had a remarkable performance on the removal of Cr(VI) from wastewater. PMID- 26877046 TI - Using sediment cores to establish targets for the remediation of aquatic environments. AB - When assigning site-specific restoration targets for deteriorating aquatic systems, it is necessary to have an understanding of the undisturbed or background state of the system. However, the site-specific characteristics of aquatic systems prior to disturbance are mostly unknown, due to the lack of historical water and sediment quality data. This study aims to introduce a method for filling this gap in our understanding, using dated sediment cores from the beds of aquatic environments. We used Bolin Billabong, a floodplain lake of the Yarra River (South-East Australia), as a case study to demonstrate the application of this method. We identified the concentrations of aluminium, cadmium, chromium, copper, iron, lead, manganese, nickel, tin and zinc at 8 cm intervals through the sediment core. This showed that aluminium, chromium, copper, iron, lead, nickel, tin and zinc concentrations in Bolin Billabong sediments significantly increased after European settlement in the river catchment in the mid-19th century. The differences between current Australian sediment quality guidelines trigger values and the background metal concentrations in Bolin Billabong sediments underscore the value of using locally relevant background toxicant concentrations when setting water and sediment quality targets. PMID- 26877047 TI - Spatial and seasonal distribution of phosphorus in the mainstem within the Three Gorges Reservoir before and after impoundment. AB - The Three Gorges Reservoir (TGR) began to store water in 2003. The water level reached 135 m in 2003, 156 m in 2006, 172 m in 2008 and 175 m (target level) in every year from 2010 through 2013. Impacts of dams on the environment are a concern all over the world. A major concern for reservoirs is phosphorus and possible eutrophication. Therefore, total phosphorus (TP) in the TGR mainstem was determined at five stations (S1-S5) from 1998 through 2013 to investigate variations of phosphorus with water level elevations. Results revealed that a new spatial and seasonal TP distribution has occurred after the impoundment. TP levels in the reach between S3 (nearly 300 km from the dam) and S5 (near the dam) have decreased sharply compared with those before the impoundment. The reduction degree of TP in wet season was greater than in dry season. Additionally, TP spatially decreased from upstream to the dam after the impoundment. The reduction of TP levels was mainly attributed to the settling of suspended solids and adsorbed phosphorus. These findings will inform research about transport and fate of phosphorus in TGR and Yangtze River. The challenge remains to implement measures to limit the release of phosphorus from sediments. PMID- 26877048 TI - Microbial degradation of N-methyl-2-pyrrolidone in surface water and bacteria responsible for the process. AB - Due to widespread utilization in many industrial spheres and agrochemicals, N methyl-2-pyrrolidone (NMP) is a potential contaminant of different surface water ecosystems. Hence, investigation was made into its aerobic microbial degradability in samples of water from a river, wetland area and spring. The results showed that the compound was degradable in all water types, and that the fastest NMP removal occurred in 4 days in river water, while in the wetland and spring samples the process was relatively slow, requiring several months to complete. Key bacterial degraders were successfully isolated in all cases, and their identification proved that pseudomonads played a major role in NMP degradation in river water, while the genera Rhodococcus and Patulibacter fulfilled a similar task in the wetland sample. Regarding spring water, degrading members of the Mesorhizobium and Rhizobium genera were found. PMID- 26877049 TI - Fault detection and isolation of sensors in aeration control systems. AB - In this paper, we consider the problem of fault detection (FD) and isolation in the aeration system of an activated sludge process. For this study, the dissolved oxygen in each aerated zone is assumed to be controlled automatically. As the basis for an FD method we use the ratio of air flow rates into different zones. The method is evaluated in two scenarios: using the Benchmark Simulation Model no. 1 (BSM1) by Monte Carlo simulations and using data from a wastewater treatment plant. The FD method shows good results for a correct and early FD and isolation. PMID- 26877050 TI - Evaluation of watershed-derived mass loads to prioritize TMDL decision-making. AB - A total maximum daily load (TMDL) for oxygen demanding substances is being implemented in the San Joaquin River (SJR) in California (USA) due to frequently occurring low dissolved oxygen conditions. The SJR is a eutrophic river, heavily impacted by agriculture. A mass balance was developed to identify the sources of oxygen-demanding substances and nutrients to the river with the objective of providing a scientific basis for management actions needed to meet TMDL requirements. Data were collected for flow and water quality and mass loads calculated for sites within the main stem of the SJR, river inputs (tributaries), and diversions in the study area. Using a quadrant analysis, tributary flows and loads are ranked to identify targets for water quality improvement efforts. Additionally, all mass loads were summed (inputs minus diversions) and compared with observed loads at the downstream limit of the study area. The mass balance analysis identifies major contributors of mass loads and mass balance closure is assessed for each constituent. These analysis methods inform the TMDL process which includes a load allocation, and is useful for determining locations for implementation of improvement projects needed to improve the health of the river. PMID- 26877051 TI - A case study of coupling upflow anaerobic sludge blanket (UASB) and ANITATM Mox process to treat high-strength landfill leachate. AB - A pilot study was conducted to study the treatability of high-strength landfill leachate by a combined process including upflow anaerobic sludge blanket (UASB), carbon removal (C-stage) moving bed biofilm reactor (MBBR) and ANITATM Mox process. The major innovation on this pilot study is the patent-pending process invented by Veolia that integrates the above three unit processes with an effluent recycle stream, which not only maintains the low hydraulic retention time to enhance the treatment performance but also reduces inhibiting effect from chemicals present in the high-strength leachate. This pilot study has demonstrated that the combined process was capable of treating high-strength leachate with efficient chemical oxygen demand (COD) and nitrogen removals. The COD removal efficiency by the UASB was 93% (from 45,000 to 3,000 mg/L) at a loading rate of 10 kg/(m(3).d). The C-stage MBBR removed an additional 500 to 1,000 mg/L of COD at a surface removal rate (SRR) of 5 g/(m(2).d) and precipitated 400 mg/L of calcium. The total inorganic nitrogen removal efficiency by the ANITA Mox reactor was about 70% at SRR of 1.0 g/(m(2).d). PMID- 26877052 TI - Experimental study on improvement effect of guide wall to water flow in bend of spillway chute. AB - In order to improve water flow in a bend of a spillway chute using a guide wall, modeling experiments with or without a guide wall under conditions of three different bend axial radii, three chute bottom slopes and three flow rates were carried out in this study. Two indexes were calculated, which are the improved water surface uniformity and the reduced rate of water surface difference in concave and convex banks of the cross-section. The results show that: (1) setting a guide wall in a bend can improve water flow in the bend because it increased the water surface uniformity of the cross-section and reduced the water surface difference in the concave and convex banks; (2) the smaller the bend axial radius, the better the water surface improvement effect will be using a guide wall; (3) the steeper the bottom slope, the more cross-sections with less water surface difference; and (4) flow rates have a great influence on water surface improvement in the bend, and the guide wall can improve water flow obviously when the water depth in the starting section of the bend is lower than the height of the guide wall. This study has important implications in engineering design of guide walls. PMID- 26877053 TI - Microbial density and diversity in constructed wetland systems and the relation to pollutant removal efficiency. AB - Microbes are believed to be at the core of the wastewater treatment processes in constructed wetlands (CWs). The aim of this study was to assess the microbial biomass carbon (MBC) and Shannon's diversity index (SDI) in the substrate of CWs planted with Phragmites australis, Hymenocallis littoralis, Canna indica and Cyperus flabelliformis, and to relate MBC and SDI to the pollutant removal in the systems. Significant higher MBC was observed in CWs with H. littoralis and C. indica than in CWs with P. australis, and the MBC differed with season and substrate depth. The microbial community in the wetlands included four phyla: Cyanobacteria, Proteobacteria, Chloroflexi, and Acidobacteria, with a more diverse community structure in wetlands with C. flabelliformis. The MBC in the substrate and the SDI of the 15-20 cm depth correlated with the removal of biochemical oxygen demand, NH4-N and NO3-N. Our results indicate that substrate SDI and MBC can both be regarded as bioindicators of the pollutant removal ability in CWs. PMID- 26877054 TI - Effect of microalgae inoculation on the start-up of microalgae-bacteria systems treating municipal, piggery and digestate wastewaters. AB - The effect of the inoculation of a microalgae-bacteria system on the removal of nutrients and organic matter using municipal, piggery and digestate wastewaters was evaluated. Three conditions for each substrate were evaluated: (1) inoculation with activated sludge and illumination, (2) inoculation with activated sludge without illumination, and (3) inoculation with activated sludge plus a native microalgae consortium under illumination. The illuminated reactors that were inoculated only with activated sludge developed microalgae after 12 operation days. In these reactors, the formation of flocs was observed affecting the sedimentation of the biomass positively. The removal of chemical oxygen demand, ammonium and phosphorous reached 84%, 65% and 77%, respectively. PMID- 26877055 TI - Implementation of an automatic and miniature on-line multi-parameter water quality monitoring system and experimental determination of chemical oxygen demand and ammonia-nitrogen. AB - An automatic, miniature and multi-parameter on-line water quality monitoring system based on a micro-spectrometer is designed and implemented. The system is integrated with the flow-batch analysis and spectrophotometric detection method. The effectiveness of the system is tested by measuring chemical oxygen demand (COD) and ammonia-nitrogen in water. The results show that the modified system provides a cost-effective, sensitive, reproducible and reliable way to measure COD and ammonia-nitrogen in water samples with automatic operation and low toxic chemical consumption. In addition, the experiment results show that the relative error of the system is less than 10%, the limit of detection is 2 mg/L COD and 0.032 mg/L ammonia-nitrogen, respectively, and the relative standard deviation was 6.6% at 15.0 mg/L COD (n = 7) and 5.0% at 0.300 mg/L ammonia-nitrogen (n = 7). Results from the newly designed system are consistent with the data collected through the Chinese national standard analysis methods. PMID- 26877056 TI - Development of an International Prostate Cancer Outcomes Registry. AB - OBJECTIVES: To establish a Prostate Cancer Outcomes Registry-Australia and New Zealand (PCOR-ANZ) for monitoring outcomes of prostate cancer treatment and care, in a cost-effective manner. MATERIALS AND METHODS: Stakeholders were recruited based on their interest, importance in achieving the monitoring and reporting of clinical practice and patient outcomes, and in amalgamation of existing registries. Each participating jurisdiction is responsible for local governance, site recruitment, data collection, and data transfer into the PCOR-ANZ. To establish each local registry, hospitals and clinicians within a jurisdiction were approached to voluntarily contribute to the registry following relevant ethical approval. Patient contact occurs following notification of prostate cancer through a hospital or pathology report, or from a cancer registry. Patient registration is based on an opt-out model. The PCOR-ANZ is a secure web-based registry adhering to ISO 27001 standards. Based on a standardised minimum data set, information on demographics, diagnosis, treatment, outcomes, and patient reported quality of life, are collected. RESULTS: Eight of nine jurisdictions have agreed to contribute to the PCOR-ANZ. Each jurisdiction has commenced implementation of necessary infrastructure to support rapid rollout. PCOR-ANZ has defined a minimum data set for collection, to enable analysis of key quality indicators that will aid in assessing clinical practice and patient focused outcomes. CONCLUSION: PCOR-ANZ will provide a useful resource of risk-adjusted evidence-based data to clinicians, hospitals, and decision makers on prostate cancer clinical practice. PMID- 26877057 TI - Genetic testing of 10 patients with features of Loeys-Dietz syndrome. AB - Inherited aortopathy, characterized with a high risk of fetal aortic aneurysms/dissections, could occur secondary to several syndromes. To identify genetic mutations and help to give a precise diagnosis, we performed a gene panel testing, involving 15 genes related to inherited aortopathy. Here we reported 10 patients, combining with the genetic testing results, were diagnosed or suspected with Loeys-Dietz syndrome, which would be the largest group of Loeys-Dietz syndrome ever reported in China till now. 10 likely pathogenic mutations or rare variants of uncertain significance were found. These results expanded the mutation spectrum of Loeys-Dietz syndrome and might be implicated in its wide phenotypic spectrum. PMID- 26877058 TI - Near-infrared spectroscopy for medical applications: Current status and future perspectives. AB - The near-infrared radiation (NIR) window, also known as the "optical window" or "therapeutic window", is the range of wavelengths that has the maximum depth of penetration in tissue. Indeed, because NIR is minimally absorbed by water and hemoglobin, spectra readings can be easily collected from the body surface. Recent reports have shown the potential of NIR spectroscopy in various medical applications, including functional analysis of the brain and other tissues, as well as an analytical tool for diagnosing diseases. The broad applicability of NIR spectroscopy facilitates the diagnosis and therapy of diseases as well as elucidating their pathophysiology. This review introduces recent advances and describes new studies in NIR to demonstrate potential clinical applications of NIR spectroscopy. PMID- 26877059 TI - Two-dimensional magnetic colloids under shear. AB - Complex rheological properties of soft disordered solids, such as colloidal gels or glasses, inspire a range of novel applications. However, the microscopic mechanisms of their response to mechanical loading are not well understood. Here, we elucidate some aspects of these mechanisms by studying a versatile model system, i.e. two-dimensional superparamagnetic colloids in a precessing magnetic field, whose structure can be tuned from a hexagonal crystal to a disordered gel network by varying the external field opening angle theta. We perform Langevin dynamics simulations subjecting these structures to a constant shear rate and observe three qualitatively different types of material response. In hexagonal crystals (theta = 0 degrees ), at a sufficiently low shear rate, plastic flow occurs via successive stress drops at which the stress releases due to the formation of dislocation defects. The gel network at theta = 48 degrees , on the contrary, via bond rearrangement and transient shear banding evolves into a homogeneously stretched network at large strains. The latter structure remains metastable after switching off of the shear. At theta = 50 degrees , the external shear makes the system unstable against phase separation and causes a failure of the network structure leading to the formation of hexagonal close packed clusters interconnected by particle chains. At a microcopic level, our simulations provide insight into some of the mechanisms by which strain localization as well as material failure occur in a simple gel-like network. Furthermore, we demonstrate that new stretched network structures can be generated by the application of shear. PMID- 26877061 TI - Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. AB - Although extracellular ATP is abundant at sites of inflammation, its role in activating inflammasome signalling in neutrophils is not well characterized. In the current study, we demonstrate that human and murine neutrophils express functional cell-surface P2X7R, which leads to ATP-induced loss of intracellular K(+), NLRP3 inflammasome activation and IL-1beta secretion. ATP-induced P2X7R activation caused a sustained increase in intracellular [Ca(2+)], which is indicative of P2X7R channel opening. Although there are multiple polymorphic variants of P2X7R, we found that neutrophils from multiple donors express P2X7R, but with differential efficacies in ATP-induced increase in cytosolic [Ca(2+)]. Neutrophils were also the predominant P2X7R-expressing cells during Streptococcus pneumoniae corneal infection, and P2X7R was required for bacterial clearance. Given the ubiquitous presence of neutrophils and extracellular ATP in multiple inflammatory conditions, ATP-induced P2X7R activation and IL-1beta secretion by neutrophils likely has a significant, wide ranging clinical impact. PMID- 26877063 TI - Consolidation With Radiation or Concurrent Chemo-Radiation After Chemotherapy Results in Durable Complete Remissions of Isolated Nodal Recurrences of Urothelial Cancer: A Case Series and Review. PMID- 26877064 TI - Motivation of Community Health Volunteers in rural Uganda: the interconnectedness of knowledge, relationship and action. AB - OBJECTIVES: In some countries, full-time Community Health Workers (CHWs) have contributed to improvements in under-5 morbidity and mortality. Based on these successes, other low- and middle-income countries are in the process of reconsidering their current health care delivery systems and integrating CHWs as a means by which to fill the gaps. It may be important to make the distinction between CHWs and Community Health Volunteers (CHVs), both of which have a unique but complementary role. While remuneration in motivation of CHWs has been extensively discussed in the literature, other motivators that may prevent high attrition rates amongst volunteers have gained less attention. The objective of this study was to understand whether full-time professional CHWs can potentially work with volunteers in the community to widen their reach and scope and if so what motivators might be of key importance to the CHVs remaining active in the field. STUDY DESIGN: CHVs were selected and trained in eight villages in East Uganda as part of a mixed-method trial conducted between March 2014 and February 2015. METHODS: Eight to twelve CHVs from each village were trained by CHWs to make home-visits to pregnant women and newborn babies and to improve hygiene. This paper reports on a) demographic data about CHVs (n = 81) and; b) in-depth interviews with retained CHVs (n = 81). RESULTS: There was a 95% retention rate amongst CHVs. In-depth interviews showed that acquisition and sharing of knowledge, relationship building and seeing health-related knowledge put into action were more important motivators than the transport allowances or the hope of gaining employment. Additionally, CHVs put what they learnt into practice by building tippy taps, having dish-racks and purifying water in their homes and as such were role models in the community. CONCLUSION: CHVs can be retained and motivated by factors other than remuneration. Gaining and sharing of knowledge with community members, relationship building and community action were inter related and ranked higher by CHVs as motivators than the hope of employment or the transport allowance. PMID- 26877065 TI - A systematic review of tobacco use among adolescents with physical disabilities. AB - OBJECTIVE: To provide a systematic review of tobacco use among adolescents with physical disabilities. STUDY DESIGN: A systematic review. METHODS: A search was performed of English articles published prior to December 2014 in the PubMed database for studies examining smoking rates among adolescents with and without physical disabilities. Ten studies were retrieved (all cross-sectional surveys) of which six compared adolescent populations from nationally representative samples and four examined those based on convenience sampling. Pooled analyses of smoking rates by disability status were performed. RESULTS: In studies from nationally representative samples (n = 6 studies), adolescents with physical disabilities were significantly more likely to use tobacco as compared to adolescents without (pooled analyses = 29.7% vs 23.3%). However, in studies from non-representative samples, adolescents with physical disabilities were less likely to use tobacco as compared to adolescents without (pooled analyses = 22.7% vs 39.1%). CONCLUSIONS: Adolescents with physical disabilities may have an increased risk of tobacco use relative to those without disabilities. Tailored tobacco use prevention and cessation strategies may be appropriate for this high risk population. Future longitudinal studies which determine factors associated with tobacco use among adolescents with different disabilities should be considered to reduce the disproportionate tobacco use in this population. PMID- 26877066 TI - Barriers to evidence-based disaster management in Nepal: a qualitative study. AB - OBJECTIVES: Globally, the incidence of natural disasters is increasing with developing countries tending to be worst affected. Implementing best practices in disaster management that are evidence-based is essential in order to improve disaster resilience and response. This study explores the barriers to evidence based disaster management encountered in Nepal. STUDY DESIGN: A qualitative study was conducted in Nepal involving interviews with key informants in the disaster management field. METHODS: Government officials, academics, programme managers, disaster management practitioners and policymakers involved in disaster management were purposively sampled and invited to interview. 11 agreed to participate and were interviewed. The face-to-face interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: The interviews uncovered population-level barriers such as contextual factors (e.g. poverty), local custom and culture, as well as community-level issues (e.g. level of engagement and understanding). System-level barriers included limited demand for, availability and accessibility of the evidence-base. The implementation of evidence was influenced by the configuration of the disaster management system and system processes. Political ownership and leadership is an essential determinant of practice. CONCLUSIONS: Several barriers to evidence-based practice in disaster management exist in Nepal. The relative influence of the different barriers varies with political determinants likely to have greater importance in countries such as Nepal where system governance and leadership is insufficiently developed. These issues affect a country's vulnerability to disasters and need to be addressed. PMID- 26877067 TI - The Italian version of Perfectionistic Self-Presentation Scale: psychometric proprieties and its associations with pathological narcissism and adult attachment in an adult non clinical sample. AB - The present study aims to evaluate the psychometric properties of the Italian version of the Perfectionistic Self-Presentation Scale (PSPS) in 447 nonclinical adult volunteers (63.5% female; mean age = 36.89 years). In our sample the PSPS total score and PSPS scales showed adequate internal consistency reliability estimates, and both the dimensionality analyses and WLSMV exploratory structural model supported the original three factors structure for PSPS items. We found a significant correlation between perfectionistic self-presentation and pathological narcissism and a significant role of attachment patterns in explaining the differences between these two constructs. Perfectionistic participants were characterized by avoidant and anxiety attachment styles, while narcissistic participants reported an anxiety style only. As a whole, our findings support the hypothesis that the Italian version of the PSPS is a reliable measure of perfectionist self-presentation in an adult community sample. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26877069 TI - Impact of Adsorption on Scanning Electrochemical Microscopy Voltammetry and Implications for Nanogap Measurements. AB - Scanning electrochemical microscopy (SECM) is a powerful tool that enables quantitative measurements of fast electron transfer (ET) kinetics when coupled with modeling predictions from finite-element simulations. However, the advent of nanoscale and nanogap electrode geometries that have an intrinsically high surface area-to-solution volume ratio realizes the need for more rigorous data analysis procedures, as surface effects such as adsorption may play an important role. The oxidation of ferrocenylmethyl trimethylammonium (FcTMA(+)) at highly oriented pyrolytic graphite (HOPG) is used as a model system to demonstrate the effects of reversible reactant adsorption on the SECM response. Furthermore, the adsorption of FcTMA(2+) species onto glass, which is often used to encapsulate ultramicroelectrodes employed in SECM, is also found to be important and affects the voltammetric tip response in a nanogap geometry. If a researcher is unaware of such effects (which may not be readily apparent in slow to moderate scan voltammetry) and analyzes SECM data assuming simple ET kinetics at the substrate and an inert insulator support around the tip, the result is the incorrect assignment of tip-substrate heights, kinetics, and thermodynamic parameters. Thus, SECM kinetic measurements, particularly in a nanogap configuration where the ET kinetics are often very fast (only just distinguishable from reversible), require that such effects are fully characterized. This is possible by expanding the number of experimental variables, including the voltammetric scan rate and concentration of redox species, among others. PMID- 26877068 TI - Race-Specific Influence of CYP4F2 on Dose and Risk of Hemorrhage Among Warfarin Users. AB - OBJECTIVE: The p.V433M in cytochrome P450 4F2 (rs2108622, CYP4F2*3) is associated with a higher warfarin dose and lower risk of hemorrhage among European Americans. We evaluate the influence of CYP4F2*3 on warfarin dose, time to target international normalized ratio (INR), and stable dose, proportion of time spent in target range (PTTR), as well as the risk of overanticoagulation and hemorrhage among European and African Americans. DESIGN: CYP4F2*3 was genotyped in 1238 patients initiated on warfarin in a prospective inception cohort. Multivariable linear regression was used to assess warfarin dose and PTTR; proportional hazards analysis was performed to evaluate time to target INR and stable dose, overanticoagulation, and hemorrhage. SETTING: Two outpatient anticoagulation clinics. PARTICIPANTS: A total of 1238 anticoagulated patients. OUTCOMES: Warfarin dose (mg/day), time to target INR and stable dose, PTTR, overanticoagulation (INR more than 4), and major hemorrhage. RESULTS: Minor allele frequency for the CYP4F2*3 variant was 30.3% among European Americans and 8.4% among African Americans. CYP4F2*3 was associated with higher dose among European Americans but not African Americans. Compared to CYP4F2*1/*1, *1/*3 was associated with a statistically nonsignificant increase in dose (4.5%, p=0.22) and *3/*3 was associated with a statistically significant increase in dose (13.2%, p=0.02). CYP4F2 genotype did not influence time to target INR, time to stable dose, or PTTR in either race group. CYP4F2*3/*3 was associated with a 31% lower risk of over anticoagulation (p=0.06). Incidence of hemorrhage was lower among participants with CYP4F2 *3/*3 compared with *1/*3 or *1/*1 (incidence rate ratio = 0.45, 95% confidence interval 0.14-1.11, p=0.09). After controlling for covariates, CYP4F2 *3/*3 was associated with a 52% lower risk of hemorrhage, although this was not statistically significant (p=0.24). CONCLUSION: Possession of CYP4F2*3 variant influences warfarin dose among European Americans but not African Americans. The CYP4F2-dose, CYP4F2-overanticoagulation, and CYP4F2 hemorrhage association follows a recessive pattern with possession of CYP4F2*3/*3 genotype likely demonstrating a protective effect. These findings need further confirmation. PMID- 26877070 TI - Psychometric validation of the Spanish version of the USS-PROM questionnaire for patients who undergo anterior urethral surgery. AB - OBJECTIVE: To translate into Spanish and validate the Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) questionnaire, assessing its psychometric properties and determining its suitability for clinical use in our community. We also assessed the potential changes in ejaculatory function using the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD). MATERIAL AND METHODS: A systematic translation of the British version was performed. Patients scheduled for anterior urethral stricture surgery between September 2014 and September 2015 were prospectively included in the study. All patients completed the questionnaire before and after the surgery. We conducted an in depth psychometric study of the questionnaire. RESULTS: We assessed the responses of a total of 40 patients. The questionnaire showed its validity, presenting an excellent negative correlation between the voiding symptom scores and the maximum flow (r=-0.6, P<.001), and also showed significant improvement in the EQ5D-VAS (visual analogue scale) and the time trade-off. For internal consistency, the Cronbach's alpha was 0.701. For the test-retest reliability, the overall intraclass correlation coefficient (ICC) was 0.974, and the ICC for each item separately ranged from 0.799 to 0.980. We observed significant improvement in all items regarding urinary symptoms and health-related quality of life (P<.001), thereby demonstrating the response capacity to changing the questionnaire. There were no significant changes in the MSHQ-EjD. CONCLUSIONS: The Spanish version of the USS-PROM questionnaire is a valid instrument for quantifying changes in voiding symptoms and the health-related quality of life of patients undergoing anterior urethral surgery. PMID- 26877071 TI - Hydrodistension plus Onabotulinumtoxin A in bladder pain syndrome refractory to conservative treatments. AB - INTRODUCTION: For bladder pain syndrome (BPS) refractory to conservative treatment, the European guidelines consider bladder hydrodistention (HD) under anaesthesia and the injection of Onabotulinumtoxin A (OnabotA) jointly. The objective of this study was to assess our experience in implementing this technique. MATERIAL AND METHODS: A prospective study of 25 patients with BPS who underwent HD plus a submucosal injection of 100 U of OnabotA in trigone. The Hunner lesions were treated endoscopically using resection or electrocoagulation. Thirty-eight procedures were performed (25 first interventions and 13 reoperations). To study the clinical change, we evaluated the subjective improvement (Treatment Benefit Scale [TBS] and Patient Global Impression of Change [PGIC] scales), the visual analogue scale (VAS) for pain, the Bladder Pain/Interstitial Cystitis Symptom Score (BPIC-SS) questionnaire and the voiding diary for 3 days. For the data analysis, we employed the Wilcoxon, Kruskal Wallis, Kaplan-Meier and log-rank tests. RESULTS: We observed subjective improvement in 21 patients (84%), which was significant in 47% of these patients, moderate in 41.2% and slight in 11.8%. Four patients did not improve. A post treatment reduction in the pain VAS (from 7.1 to 1.8 points; P=.001), in daytime (from 11.8 to 7.5; P=.012) and night-time (from 5.9 to 3.6; P=.003) voiding frequency and in the BPIC-SS (from 27.9 to 11.2 points; P=.042). The degree of improvement was not related to age, the presence of bladder lesions or the treatment of relapses. The median duration of improvement was 7 months (95% CI 5.69-8.31), although this duration was somewhat longer for the patients younger than 65 years. Mild complications occurred in 23.7% of the cases. CONCLUSIONS: The joint implementation of HD plus OnabotA is a valid therapeutic option in refractory BPS, which provides good clinical results and maintains its effectiveness in retreatments. PMID- 26877072 TI - Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I. AB - Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture. PMID- 26877073 TI - Voluntary vaccination strategy and the spread of sexually transmitted diseases. AB - In this work, we investigate the spread and control of sexually transmitted diseases when a game-theory based vaccination strategy is involved. An individual's decision on vaccination uptake may follow a cost-benefit analysis since the individual obtains immunity against the disease from the vaccination and, at the same time, may have some perceived side effects. Evolutionary game theory is integrated into the epidemic model to reveal the relationship between individuals' voluntary decisions on vaccination uptake and the spread and control of such diseases. We show that decreasing the perceived cost of taking vaccine or increasing the payoff from social obligation is beneficial to controlling the disease. It is also shown how the "degree of rationality" of males and females affects the disease spread through the net payoff of the game. In particular, individual awareness of the consequences of the disease on the infectives also contributes to slowing down the disease spread. By analyzing an asymmetric version of our evolutionary game, it is shown that the disease is better controlled when individuals are more sensitive to fitness differences when net payoff is positive than when it is negative. PMID- 26877074 TI - Stochasticity and bifurcations in a reduced model with interlinked positive and negative feedback loops of CREB1 and CREB2 stimulated by 5-HT. AB - The cyclic AMP (cAMP)-response element-binding protein (CREB) family of transcription factors is crucial in regulating gene expression required for long term memory (LTM) formation. Upon exposure of sensory neurons to the neurotransmitter serotonin (5-HT), CREB1 is activated via activation of the protein kinase A (PKA) intracellular signaling pathways, and CREB2 as a transcriptional repressor is relieved possibly via phosphorylation of CREB2 by mitogen-activated protein kinase (MAPK). Song et al. [18] proposed a minimal model with only interlinked positive and negative feedback loops of transcriptional regulation by the activator CREB1 and the repressor CREB2. Without considering feedbacks between the CREB proteins, Pettigrew et al. [8] developed a computational model characterizing complex dynamics of biochemical pathways downstream of 5-HT receptors. In this work, to describe more simply the biochemical pathways and gene regulation underlying 5-HT-induced LTM, we add the important extracellular sensitizing stimulus 5-HT as well as the product Ap-uch into the Song's minimal model. We also strive to examine dynamical properties of the gene regulatory network under the changing concentration of the stimulus, [5 HT], cooperating with the varying positive feedback strength in inducing a high state of CREB1 for the establishment of long-term memory. Different dynamics including monostability, bistability and multistability due to coexistence of stable steady states and oscillations is investigated by means of codimension-2 bifurcation analysis. At the different positive feedback strengths, comparative analysis of deterministic and stochastic dynamics reveals that codimension-1 bifurcation with respect to [5-HT] as the parameter can predict diverse stochastic behaviors resulted from the finite number of molecules, and the number of CREB1 molecules more and more preferentially resides near the high steady state with increasing [5-HT], which contributes to long-term memory formation. PMID- 26877075 TI - Random migration processes between two stochastic epidemic centers. AB - We consider the epidemic dynamics in stochastic interacting population centers coupled by random migration. Both the epidemic and the migration processes are modeled by Markov chains. We derive explicit formulae for the probability distribution of the migration process, and explore the dependence of outbreak patterns on initial parameters, population sizes and coupling parameters, using analytical and numerical methods. We show the importance of considering the movement of resident and visitor individuals separately. The mean field approximation for a general migration process is derived and an approximate method that allows the computation of statistical moments for networks with highly populated centers is proposed and tested numerically. PMID- 26877076 TI - Japanese nurses' perception of their preparedness for disasters: Quantitative survey research on one prefecture in Japan. AB - AIM: The objective of this study was to explore nurses' perceptions regarding their knowledge, skills, and preparedness for disasters and how they acquired their knowledge about disaster preparation using a quantitative approach. METHODS: A descriptive cross-sectional survey using the Disaster Preparedness Evaluation Tool was distributed to nurses in six hospitals (three private, three public) throughout Miyazaki Prefecture located in southern Japan. RESULTS: Nine hundred and seventy-three surveys (87.4%) were returned. Seventy-two were eliminated leaving 902 (81.0%) for data analysis. Mean scores for preparedness, response abilities, and evaluation all scored below normal on a 6 point Likert scale (2.63, 2.02, and 2.05, respectively). Overall, nurses felt they were not able to respond in a variety of disaster situations, were aware of their workplace emergency disaster plan, but did not think they could execute them, and were not aware of the level of preparedness of the healthcare systems in their communities. CONCLUSION: The amount of information nurses need to know on the knowledge, skills, and preparation of disasters are in great need. Such skills are understood, but lacking for various reasons. In-house programs for nurses to learn more about disaster nursing are needed. Furthermore, a curriculum for disaster preparedness for undergraduate and graduate nursing programs would also help these future nurses gain more information earlier on to better prepare them for possible disaster situations in their future careers. PMID- 26877078 TI - A randomized controlled trial of web-based training to increase activity in children with cerebral palsy. AB - AIM: To determine the efficacy of web-based training on activity capacity and performance in children with unilateral cerebral palsy (CP). METHOD: In a matched pairs randomized waitlist controlled trial, independently ambulant children and adolescents with unilateral CP were allocated to receive 30 minutes of training (intervention) 6 days per week, or usual care (waitlist control) for 20 weeks. Activity capacity was assessed using maximal repetitions of functional strength tasks and 6-minute walk test (6MWT); performance using 4-day ActiGraph GT3X+ accelerometer records at baseline and 20 weeks. Data were analysed by intention to treat comparing between groups using hierarchical linear modelling. RESULTS: Participants were n=101, 52 males, mean age 11 years 3 months (SD 2y 4mo). Intervention participants completed a mean 32.4 hours (SD 17.2) of training, associated with significant improvements in functional strength (mean difference 19.3 repetitions; 95% confidence interval [CI] 10.8-27.7; p<0.001) and 6MWT distance (mean difference 38.9m; 95% CI 12.3-51.9; p<0.001) compared with the control group at 20 weeks, although not activity performance (p>0.05). INTERPRETATION: Training was effective at increasing functional strength and walking endurance in independently ambulant children with unilateral CP. This did not translate into improvements in activity performance. PMID- 26877079 TI - The Role of Dopamine in Value-Based Attentional Orienting. AB - Reward learning gives rise to strong attentional biases. Stimuli previously associated with reward automatically capture visual attention regardless of intention. Dopamine signaling within the ventral striatum plays an important role in reward learning, representing the expected reward initiated by a cue. How dopamine and the striatum may be involved in maintaining behaviors that have been shaped by reward learning, even after reward expectancies have changed, is less well understood. Nonspecific measures of brain activity have implicated the striatum in value-based attention. However, the neurochemical mechanisms underlying the attentional priority of learned reward cues remain unexplored. Here, we investigated the contribution of dopamine to value-based attention using positron emission tomography (PET) with [(11)C]raclopride. We show that, in the explicit absence of reward, the magnitude of attentional capture by previously reward-associated but currently task-irrelevant distractors is correlated across individuals with changes in available D2/D3 dopamine receptors (presumably due to intrasynaptic dopamine) linked to distractor processing within the right caudate and posterior putamen. Our findings provide direct evidence linking dopamine signaling within the striatum to the involuntary orienting of attention, and specifically to the attention-grabbing quality of learned reward cues. These findings also shed light on the neurochemical basis of individual susceptibility to value-driven attentional capture, which is known to play a role in addiction. More broadly, the present study highlights the value and feasibility of using PET to relate changes in the release of a neurotransmitter to learning-dependent changes in healthy adults. PMID- 26877080 TI - Shoot-to-Root Mobile Transcription Factor HY5 Coordinates Plant Carbon and Nitrogen Acquisition. AB - Coordination of shoot photosynthetic carbon fixation with root inorganic nitrogen uptake optimizes plant performance in a fluctuating environment [1]. However, the molecular basis of this long-distance shoot-root coordination is little understood. Here we show that Arabidopsis ELONGATED HYPOCOTYL5 (HY5), a bZIP transcription factor that regulates growth in response to light [2, 3], is a shoot-to-root mobile signal that mediates light promotion of root growth and nitrate uptake. Shoot-derived HY5 auto-activates root HY5 and also promotes root nitrate uptake by activating NRT2.1, a gene encoding a high-affinity nitrate transporter [4]. In the shoot, HY5 promotes carbon assimilation and translocation, whereas in the root, HY5 activation of NRT2.1 expression and nitrate uptake is potentiated by increased carbon photoassimilate (sucrose) levels. We further show that HY5 function is fluence-rate modulated and enables homeostatic maintenance of carbon-nitrogen balance in different light environments. Thus, mobile HY5 coordinates light-responsive carbon and nitrogen metabolism, and hence shoot and root growth, in a whole-organismal response to ambient light fluctuations. PMID- 26877077 TI - Mechanobiology of TGFbeta signaling in the skeleton. AB - Physical and biochemical cues play fundamental roles in the skeleton at both the tissue and cellular levels. The precise coordination of these cues is essential for skeletal development and homeostasis, and disruption of this coordination can drive disease progression. The growth factor TGFbeta is involved in both the regulation of and cellular response to the physical microenvironment. It is essential to summarize the current findings regarding the mechanisms by which skeletal cells integrate physical and biochemical cues so that we can identify and address remaining gaps that could ultimately improve skeletal health. In this review, we describe the role of TGFbeta in mechanobiological signaling in bone and cartilage at the tissue and cellular levels. We provide detail on how static and dynamic physical cues at the macro-level are transmitted to the micro-level, ultimately leading to regulation at each level of the TGFbeta pathway and to cell differentiation. The continued integration of engineering and biological approaches is needed to answer many remaining questions, such as the mechanisms by which cells generate a coordinated response to physical and biochemical cues. We propose one such mechanism, through which the combination of TGFbeta and an optimal physical microenvironment leads to synergistic induction of downstream TGFbeta signaling. PMID- 26877081 TI - Effective Modulation of Male Aggression through Lateral Septum to Medial Hypothalamus Projection. AB - Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause "septal rage," a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of LS-mediated modulation of aggression, we examined the influence of LS input on the cells in and around the ventrolateral part of the ventromedial hypothalamus (VMHvl)-a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus, LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression. PMID- 26877082 TI - ER-PM Contacts Define Actomyosin Kinetics for Proper Contractile Ring Assembly. AB - The cortical endoplasmic reticulum (ER), an elaborate network of tubules and cisternae [1], establishes contact sites with the plasma membrane (PM) through tethering machinery involving a set of conserved integral ER proteins [2]. The physiological consequences of forming ER-PM contacts are not fully understood. Here, we reveal a kinetic restriction role of ER-PM contacts over ring compaction process for proper actomyosin ring assembly in Schizosaccharomyces pombe. We show that fission yeast cells deficient in ER-PM contacts exhibit aberrant equatorial clustering of actin cables during ring assembly and are particularly susceptible to compromised actin filament crosslinking activity. Using quantitative image analyses and computer simulation, we demonstrate that ER-PM contacts function to modulate the distribution of ring components and to constrain their compaction kinetics. We propose that ER-PM contacts have evolved as important physical modulators to ensure robust ring assembly. PMID- 26877083 TI - How Wasps Acquire and Use Views for Homing. AB - Nesting insects perform learning flights to establish a visual representation of the nest environment that allows them to subsequently return to the nest. It has remained unclear when insects learn what during these flights, what determines their overall structure, and, in particular, how what is learned is used to guide an insect's return. We analyzed learning flights in ground-nesting wasps (Sphecidae: Cerceris australis) using synchronized high-speed cameras to determine 3D head position and orientation. Wasps move along arcs centered on the nest entrance, whereby rapid changes in gaze assure that the nest is seen at lateral positions in the left or the right visual field. Between saccades, the wasps translate along arc segments around the nest while keeping gaze fixed. We reconstructed panoramic views along the paths of learning and homing wasps to test specific predictions about what wasps learn during their learning flights and how they use this information to guide their return. Our evidence suggests that wasps monitor changing views during learning flights and use the differences they experience relative to previously encountered views to decide when to begin a new arc. Upon encountering learned views, homing wasps move left or right, depending on the nest direction associated with that view, and in addition appear to be guided by features on the ground close to the nest. We test our predictions on how wasps use views for homing by simulating homing flights of a virtual wasp guided by views rendered in a 3D model of a natural wasp environment. PMID- 26877084 TI - Adaptive Radiation in Socially Advanced Stem-Group Ants from the Cretaceous. AB - Across terrestrial ecosystems, modern ants are ubiquitous. As many as 94 out of every 100 individual arthropods in rainforests are ants, and they constitute up to 15% of animal biomass in the Amazon. Moreover, ants are pervasive agents of natural selection as over 10,000 arthropod species are specialized inquilines or myrmecomorphs living among ants or defending themselves through mimicry. Such impact is traditionally explained by sociality: ants are the first major group of ground-dwelling predatory insects to become eusocial, increasing efficiency of tasks and establishing competitive superiority over solitary species. A wealth of specimens from rich deposits of 99 million-year-old Burmese amber resolves ambiguity regarding sociality and diversity in the earliest ants. The stem-group genus Gerontoformica maintained distinct reproductive castes including morphotypes unknown in solitary aculeate (stinging) wasps, providing insight into early behavior. We present rare aggregations of workers, indicating group recruitment as well as an instance of interspecific combat; such aggression is a social feature of modern ants. Two species and an unusual new genus are described, further expanding the remarkable diversity of early ants. Stem-group ants are recovered as a paraphyletic assemblage at the base of modern lineages varying greatly in size, form, and mouthpart structure, interpreted here as an adaptive radiation. Though Cretaceous stem-group ants were eusocial and adaptively diverse, we hypothesize that their extinction resulted from the rise of competitively superior crown-group taxa that today form massive colonies, consistent with Wilson and Holldobler's concept of "dynastic succession." PMID- 26877085 TI - Morphologically Specialized Termite Castes and Advanced Sociality in the Early Cretaceous. AB - A hallmark of animals that are eusocial, or those with advanced sociality, is reproductive specialization into worker and queen castes. In the most derived societies, these divisions are essentially fixed and in some arthropods, include further specialization--a tripartite system with a soldier caste that defends the colony. Eusociality has originated numerous times among insects but is believed to have appeared first in the termites (Isoptera), in the Early Cretaceous. However, all termites known from the Cretaceous have, until now, only been winged reproductives (alates and dealates); the earliest soldiers and definitive workers were known from just the Miocene (ca. 17-20 million years ago [mya]). Here, we report six termite species preserved in Early Cretaceous (ca. 100 mya) amber from Myanmar, one described as Krishnatermes yoddha gen. et sp. nov., comprising the worker/pseudergate, winged reproductive, and soldier, and a second species, Gigantotermes rex gen. et sp. nov., based on one of the largest soldier termites yet known. Phylogenetic analysis indicates that Krishnatermes are in the basal "Meiatermes-grade" of Cretaceous termites. Workers/pseudergates of another four species are briefly described, but not named. One of these workers/pseudergates reveals that ants--the most serious enemies of modern termites--lived in close proximity to termites in the Burmese paleofauna. These discoveries demonstrate the Mesozoic antiquity of specialized termite caste systems and corroborate that among all social species, termites probably had the original societies. PMID- 26877086 TI - Four Individually Identified Paired Dopamine Neurons Signal Reward in Larval Drosophila. AB - Dopaminergic neurons serve multiple functions, including reinforcement processing during associative learning [1-12]. It is thus warranted to understand which dopaminergic neurons mediate which function. We study larval Drosophila, in which only approximately 120 of a total of 10,000 neurons are dopaminergic, as judged by the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis [5, 13]. Dopaminergic neurons mediating reinforcement in insect olfactory learning target the mushroom bodies, a higher-order "cortical" brain region [1-5, 11, 12, 14, 15]. We discover four previously undescribed paired neurons, the primary protocerebral anterior medial (pPAM) neurons. These neurons are TH positive and subdivide the medial lobe of the mushroom body into four distinct subunits. These pPAM neurons are acutely necessary for odor-sugar reward learning and require intact TH function in this process. However, they are dispensable for aversive learning and innate behavior toward the odors and sugars employed. Optogenetical activation of pPAM neurons is sufficient as a reward. Thus, the pPAM neurons convey a likely dopaminergic reward signal. In contrast, DL1 cluster neurons convey a corresponding punishment signal [5], suggesting a cellular division of labor to convey dopaminergic reward and punishment signals. On the level of individually identified neurons, this uncovers an organizational principle shared with adult Drosophila and mammals [1-4, 7, 9, 10] (but see [6]). The numerical simplicity and connectomic tractability of the larval nervous system [16-19] now offers a prospect for studying circuit principles of dopamine function at unprecedented resolution. PMID- 26877088 TI - Globally distributed Xyleborus species reveal recurrent intercontinental dispersal in a landscape of ancient worldwide distributions. AB - BACKGROUND: Invasive species can have devastating effects on native ecosystems and therefore impose a significant threat to human welfare. The introduction rate of invasive species has accelerated dramatically in recent times due to human activity (anthropogenic effects), with a steadily growing pool of widespread tramp species. We present an in-depth analysis of four pantropical species of Xyleborus ambrosia beetles (Xyleborus volvulus, Xyleborus perforans, Xyleborus ferrugineus, and Xyleborus affinis) with similar ecology (fungus cultivation in dead wood), reproductive biology (permanent inbreeding) and genetic system (haplodiploidy). The unique combination of reproductive traits and broad host plant usage pre-adapts these beetles for colonizing of new areas. RESULTS: We found that all four species were broadly distributed long before human-assisted dispersal became common, and that the impact of anthropogenic effects varied among the species. For X. volvulus, X. perforans, and X. affinis there was evidence of ancient establishment in numerous regions, but also of abundant recent introductions into previously colonized areas. For X. ferrugineus, we found clear biogeographical structuring of old clades, but little evidence for recent successful introductions. CONCLUSIONS: Our results indicate that current human-aided transoceanic dispersal has strongly affected the genetic makeup of three of the species in this study. However, current biogeographical patterns of all four species are equally, if not more strongly, influenced by ancient establishment on different continents. PMID- 26877089 TI - Overcoming Short-Circuit in Lead-Free CH3NH3SnI3 Perovskite Solar Cells via Kinetically Controlled Gas-Solid Reaction Film Fabrication Process. AB - The development of Sn-based perovskite solar cells has been challenging because devices often show short-circuit behavior due to poor morphologies and undesired electrical properties of the thin films. A low-temperature vapor-assisted solution process (LT-VASP) has been employed as a novel kinetically controlled gas-solid reaction film fabrication method to prepare lead-free CH3NH3SnI3 thin films. We show that the solid SnI2 substrate temperature is the key parameter in achieving perovskite films with high surface coverage and excellent uniformity. The resulting high-quality CH3NH3SnI3 films allow the successful fabrication of solar cells with drastically improved reproducibility, reaching an efficiency of 1.86%. Furthermore, our Kelvin probe studies show the VASP films have a doping level lower than that of films prepared from the conventional one-step method, effectively lowering the film conductivity. Above all, with (LT)-VASP, the short circuit behavior often obtained from the conventional one-step-fabricated Sn based perovskite devices has been overcome. This study facilitates the path to more successful Sn-perovskite photovoltaic research. PMID- 26877087 TI - The Neuronal Kinesin UNC-104/KIF1A Is a Key Regulator of Synaptic Aging and Insulin Signaling-Regulated Memory. AB - Aging is the greatest risk factor for a number of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Furthermore, normal aging is associated with a decline in sensory, motor, and cognitive functions. Emerging evidence suggests that synapse alterations, rather than neuronal cell death, are the causes of neuronal dysfunctions in normal aging and in early stages of neurodegenerative diseases. However, little is known about the mechanisms underlying age-related synaptic decline. Here, we uncover a surprising role of the anterograde molecular motor UNC-104/KIF1A as a key regulator of neural circuit deterioration in aging C. elegans. Through analyses of synapse protein localization, synaptic transmission, and animal behaviors, we find that reduced function of UNC-104 accelerates motor circuit dysfunction with age, whereas upregulation of UNC-104 significantly improves motor function at advanced ages and also mildly extends lifespan. In addition, UNC-104-overexpressing animals outperform wild-type controls in associative learning and memory tests. Further genetic analyses suggest that UNC-104 functions downstream of the DAF-2-signaling pathway and is regulated by the FOXO transcription factor DAF-16, which contributes to the effects of DAF-2 in neuronal aging. Together, our cellular, electrophysiological, and behavioral analyses highlight the importance of axonal transport in the maintenance of synaptic structural integrity and function during aging and raise the possibility of targeting kinesins to slow age-related neural circuit dysfunction. PMID- 26877090 TI - Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function In Vitro. AB - In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 +/- 9.8%, 87.4 +/- 5.8%, and 88.6 +/- 4.5%, and survival rates were 60.3 +/- 6.8%, 65.3 +/- 3.0%, and 75.8 +/- 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 +/- 1.6, 9.4 +/- 3.8, and 23.5 +/- 12.4 uIU/islet, and interleukin-6 (IL 6) secretions were 3.0 +/- 0.7, 5.1 +/- 1.2, and 7.3 +/- 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix. PMID- 26877092 TI - Implementing evidence-driven individualized treatment plans within Morquio A Syndrome. AB - Morquio A Syndrome (mucopolysaccharidosis IVA [MPS IVA]) is an inherited, autosomal recessive lysosomal storage disorder that occurs in ~1 in 200,000 to 300,000 live births.(1) (Online access http://www.elseviercme.com/559) Individuals with Morquio A Syndrome have mutations in the gene that encodes N acetylgalactosamine-6-sulfate sulfatase (GALNS), an enzyme responsible for the metabolism of the glycosaminoglycans (GAGs) keratin sulfate and chondroitin-6 sulfate.(2-4) Reduced activity or lack of GALNS leads to cellular and tissue accumulation of these GAGs to result in progressive, multisystem dysfunction and impaired functional capacity.(5) Individuals with Morquio A Syndrome suffer from a broad spectrum of impairment, including a variety of widespread skeletal abnormalities, respiratory compromise, valvular heart disease, visual and auditory impairments, and dental abnormalities.(6-8) Cognition is not typically affected.(9) Morquio A Syndrome exhibits extensive allelic heterogeneity, which results in extensive clinical heterogeneity.(2-4) This educational intervention on the management of patients with Morquio A Syndrome provides updated information and guidelines concerning the early and accurate diagnosis as well as an earlier intervention to improve patient outcomes. The activity is based on a live satellite symposium conducted during the 2015 official ACMG Annual Clinical Genetics Meeting program. Recent advances in the science of enzyme replacement therapies have presented opportunities for pharmacological interventions that improve quality of life. Clinicians will be updated on the clinical trial data and practical solutions for applying newer therapeutics to daily practice. Strategies to manage cardiopulmonary comorbidities and recommendations for the ideal clinical care model will wrap up this informative and up-to-date review of Morquio A Syndrome. This CME activity is also available through the Website of Molecular Genetics and Metabolism. Click on the CME button in the navigation bar for full access. Or access: http://www.elseviercme.com/559. PMID- 26877091 TI - Critical POU domain residues confer Oct4 uniqueness in somatic cell reprogramming. AB - The POU domain transcription factor Oct4 plays critical roles in self-renewal and pluripotency of embryonic stem cells (ESCs). Together with Sox2, Klf4 and c-Myc, Oct4 can reprogram any other cell types to pluripotency, in which Oct4 is the only factor that cannot be functionally replaced by other POU family members. To investigate the determinant elements of Oct4 uniqueness, we performed Ala scan on all Ser, Thr, Tyr, Lys and Arg of murine Oct4 by testing their capability in somatic cell reprogramming. We uncovered a series of residues that are important for Oct4 functionality, in which almost all of these key residues are within the POU domains making direct interaction with DNA. The Oct4 N- and C-terminal transactivation domains (TADs) are not unique and could be replaced by the Yes associated protein (YAP) TAD domain to support reprogramming. More importantly, we uncovered two important residues that confer Oct4 uniqueness in somatic cell reprogramming. Our systematic structure-function analyses bring novel mechanistic insight into the molecular basis of how critical residues function together to confer Oct4 uniqueness among POU family for somatic cell reprogramming. PMID- 26877093 TI - 25 years of Eye Movement Desensitization and Reprocessing (EMDR): The EMDR therapy protocol, hypotheses of its mechanism of action and a systematic review of its efficacy in the treatment of post-traumatic stress disorder. AB - Eye movement desensitization and reprocessing (EMDR) is a relatively new psychotherapy that has gradually gained popularity for the treatment of post traumatic stress disorder. In the present work, the standardised EMDR protocol is introduced, along with current hypotheses of its mechanism of action, as well as a critical review of the available literature on its clinical effectiveness in adult post-traumatic stress disorder. A systematic review of the published literature was performed using PubMed and PsycINFO databases with the keywords "eye movement desensitization and reprocessing" and "post-traumatic stress disorder" and its abbreviations "EMDR" and "PTSD". Fifteen randomised controlled trials of good methodological quality were selected. These studies compared EMDR with unspecific interventions, waiting lists, or specific therapies. Overall, the results of these studies suggest that EMDR is a useful, evidence-based tool for the treatment of post-traumatic stress disorder, in line with recent recommendations from different international health organisations. PMID- 26877096 TI - Corrigendum. PMID- 26877094 TI - Effect of bisphenol A on morphology, apoptosis and proliferation in the resting mammary gland of the adult albino rat. AB - Bisphenol A (BPA) is a synthetic oestrogen that is extensively used in a wide range of daily used plastic products. This makes it one of the environmental chemicals that may have impact on human health. Due to its oestrogenic effect, BPA might affect the mammary gland. This study aimed to investigate the influence of BPA on the histological structure of the mammary gland of the adult female albino rat and its effect on epithelial cell proliferation and apoptosis status, in addition to its possible modulating effect on estrogen receptor expression. Thirty female adult albino rats were divided into control and experimental groups. The rats in the experimental group were gavaged with 5 mg/kg BPA daily for 8 weeks. The mammary glands were dissected and processed for histological and immunohistochemical stains for Ki-67, activated caspase-3 and estrogen receptor alpha (ER-alpha). BPA induced an increase in the number and size of the acini and ducts in the mammary gland of treated rats with hyperplasia of their lining epithelial cells. The collagen fibre content was significantly increased in the connective tissue stroma separating the ducts. Immunohistochemical results showed a significant increase in Ki-67 and caspase-3, but a non-significant increase in ER-alpha expression. Bisphenol A induced structural changes and affected the proliferation rate of mammary glands, so it might be one of the predisposing factors for breast cancer. PMID- 26877095 TI - Restaurant Menu Labeling Policy: Review of Evidence and Controversies. AB - In response to high rates of obesity in the USA, several American cities, counties, and states have passed laws requiring restaurant chains to post labels identifying the energy content of items on menus, and nationwide implementation of menu labeling is expected in late 2016. In this review, we identify and summarize the results of 16 studies that have assessed the impact of real-world numeric calorie posting. We also discuss several controversies surrounding the US Food and Drug Administration's implementation of federally mandated menu labeling. Overall, the evidence regarding menu labeling is mixed, showing that labels may reduce the energy content of food purchased in some contexts, but have little effect in other contexts. However, more data on a range of ong-term consumption habits and restaurant responses is needed to fully understand the impact menu labeling laws will have on the US population's diet. PMID- 26877097 TI - 99mTc-labelled anti-CD11b SPECT/CT imaging allows detection of plaque destabilization tightly linked to inflammation. AB - It remains challenging to predict the risk of rupture for a specific atherosclerotic plaque timely, a thrombotic trigger tightly linked to inflammation. CD11b, is a biomarker abundant on inflammatory cells, not restricted to monocytes/macrophages. In this study, we fabricated a probe named as (99m)Tc-MAG3-anti-CD11b for detecting inflamed atherosclerotic plaques with single photon emission computed tomography/computed tomography (SPECT/CT). The ApoE-knockout (ApoE(-/-)) mice were selected to establish animal models, with C57BL/6J mice used for control. A higher CD11b(+)-cell recruitment with higher CD11b expression and more serious whole-body inflammatory status were identified in ApoE(-/-) mice. The probe showed high in vitro affinity and specificity to the Raw-264.7 macrophages, as well as inflammatory cells infiltrated in atherosclerotic plaques, either in ex vivo fluorescent imaging or in in vivo micro-SPECT/CT imaging, which were confirmed by ex vivo planar gamma imaging, Oil Red-O staining and CD11b-immunohistochemistry staining. A significant positive relationship was identified between the radioactivity intensity on SPECT/CT images and the CD11b expression in plaques. In summary, this study demonstrates the feasibility of anti-CD11b antibody mediated noninvasive SPECT/CT imaging of inflammatory leukocytes in murine atherosclerotic plaques. This imaging strategy can identify inflammation-rich plaques at risk for rupture and evaluate the effectiveness of inflammation-targeted therapies in atheroma. PMID- 26877099 TI - Factors Associated with Contraceptive Use Differ between Younger and Older African-American Female Adolescents. AB - STUDY OBJECTIVE: To examine differences in factors associated with contraceptive use between younger and older adolescent age groups, which has not previously been well described. DESIGN: Age group-specific analyses were performed on cross sectional survey data to identify factors associated with any contraceptive use at last sex among younger (14- to 16-year-old) and older (17- to 19-year-old) sexually active African American female adolescents; interaction analyses were used to assess whether these associations differed by age. SETTING: Adolescent reproductive health clinic in Atlanta, Georgia. PARTICIPANTS: Sexually active African American female adolescents 14-19 years of age. INTERVENTIONS: No intervention tested; cross-sectional design. MAIN OUTCOME MEASURE: Self-reported contraceptive use during most recent vaginal sex with a male partner. RESULTS: The prevalence of contraceptive use at last sex was identical in both groups; however, factors associated with contraceptive use differed according to age. The only factor associated with contraceptive use in both age groups was involvement in decisions about sexual health in the most recent relationship. Associations between factors and contraceptive use significantly differed according to age. History of sexually transmitted infection, age difference with partner, discussion of condoms with partner, and concurrent partners were important factors among younger adolescents; worry about pregnancy and discussion of birth control with partner were important among older adolescents. CONCLUSION: Factors associated with contraceptive use at last sex differ according to adolescent age; this should be considered when designing counseling and interventions for teens, as well as research. PMID- 26877100 TI - Cytotoxic cochlioquinone derivatives from the endophytic fungus Bipolaris sorokiniana derived from Pogostemon cablin. AB - Chemical investigation of the liquid culture of the endophytic fungus Bipolaris sorokiniana A606, which was isolated from the medicinal plant Pogostemon cablin resulted in the isolation of four new cytotoxic compounds, named isocochlioquinones D-E (1-2) and cochlioquinones G-H (3-4), along with five known cochlioquinone analogues (5-9). Their structures were determined on the basis of extensive spectroscopic analysis. Isocochlioquinone D (1) possessed a rare benzothiazin-3-one moiety and cochlioquinone G (3) was the first example of cochlioquinones bearing an indole-4,7-dione fragment. All of the isolates (1-9) were evaluated for their cytotoxic activities against MCF-7, NCI-H460, SF-268 and HepG-2 tumor cell lines by the sulforhodamine B (SRB) assay. Compounds 4 and 6-9, featuring a cochlioquinone core, exhibited potent cytotoxicities in vitro against the four tumor cell lines, and a preliminary structure-activity relationship of these compounds was also discussed. PMID- 26877101 TI - Diagnostic reliability in schizoaffective disorder. PMID- 26877098 TI - Extracellular Matrix Rigidity-dependent Sphingosine-1-phosphate Secretion Regulates Metastatic Cancer Cell Invasion and Adhesion. AB - Dynamic interaction between cancer cells and the surrounding microenvironment is critical for cancer progression via changes in cellular behavior including alteration of secreted molecules. However, the molecular mechanisms underlying the influence exerted by the cancer microenvironment on secretion of molecules during cancer progression remain largely unknown. In this study, we report that secretion of spingsine-1-phosphate (S1P) and its regulator, SphK1 expression is dependent of the substrate rigidity, which is critical for the balance between cancer cell invasion and adhesion. Conditioned media (CM) of MDA-MB-231, an aggressive breast cancer cell obtained from soft substrate (~0.5 kPa) induced chemo-attractive invasion, while CM obtained from stiff substrate (~2.5 kPa) increased cell adhesion instead. We found that the expression of SphK1 is upregulated in the stiff substrate, resulting in an increase in S1P levels in the CM. We also found that upregulation of SphK1 expression in the stiff substrate is dominant in metastatic cancer cells but not in primary cancer cells. These results suggest that alterations in the mechanical environment of the ECM surrounding the tumor cells actively regulate cellular properties such as secretion, which in turn, may contribute to cancer progression. PMID- 26877102 TI - Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. AB - Inactivation of cancer stem cells (CSCs) is of utmost importance for tumor cure after radiotherapy. An increasing body of evidence complies with a higher radioresistance of CSCs compared to the mass of tumor cells, supporting the use of CSC related biomarkers for prediction of radiotherapy outcome. Treatment individualization strategies for patient groups with vastly different risk of recurrence will most likely require application of more than one biomarker. Specifically, inclusion of established biomarkers like tumor size for primary radio(chemo)therapy or human papilloma virus (HPV) infection status in head and neck squamous cell carcinoma seems to be of very high relevance. The high heterogeneity of CSC subclones along with changes of the functional behavior of individual tumors under treatment underlines the importance of the selection of the optimal timepoint(s) of biomarker evaluation, but also provides a potential therapeutic target for combined treatment approaches with irradiation. PMID- 26877103 TI - When barriers ignore the "rule-of-five". AB - Why are a few drugs with properties beyond the rule of 5 (bRo5) absorbed across the intestinal mucosa while most other bRo5 compounds are not? Are such exceptional bRo5 compounds exclusively taken up by carrier-mediated transport or are they able to permeate the lipid bilayer (passive lipoidal diffusion)? Our experimental data with liposomes indicate that tetracycline, which violates one rule of the Ro5, and rifampicin, violating three of the rules, significantly permeate a phospholipid bilayer with kinetics similar to labetalol and metoprolol, respectively. Published data from experimental work and molecular dynamics simulations suggest that the formation of intramolecular H-bonds and the possibility to adopt an elongated shape besides the presence of a significant fraction of net neutral species facilitate lipid bilayer permeation. As an alternative to lipid bilayer permeation, carrier proteins can be targeted to improve absorption, with the potential drawbacks of drug-drug interactions and non-linear pharmacokinetics. PMID- 26877104 TI - Cognitive mechanisms for responding to mimicry from others. AB - Compared to our understanding of neurocognitive processes involved producing mimicry, the downstream consequences of being mimicked are less clear. A wide variety of positive consequences of mimicry, such as liking and helping, have been reported in behavioural research. However, an in-depth review suggests the link from mimicry to liking and other positive outcomes may be fragile. Positive responses to mimicry can break down due to individual factors and social situations where mimicry may be unexpected. It remains unclear how the complex behavioural effects of mimicry relate to neural systems which respond to being mimicked. Mimicry activates regions associated with mirror properties, self-other processing and reward. In this review, we outline three potential models linking these regions with cognitive consequences of being mimicked. The models suggest that positive downstream consequences of mimicry may depend upon self-other overlap, detection of contingency or low prediction error. Finally, we highlight limitations with traditional research designs and suggest alternative methods for achieving highly ecological validity and experimental control. We also highlight unanswered questions which may guide future research. PMID- 26877105 TI - Dynamic construction of the neural networks underpinning empathy for pain. AB - When people witness or imagine the pain of another person, their nervous system may react as if they were feeling that pain themselves. Early neuroscientific evidence indicates that the firsthand and vicarious experiences of pain share largely overlapping neural structures, which typically correspond to the lateral and medial brain regions that encode the sensory and the affective qualities of pain. Such neural circuitry is highly malleable and allows people to flexibly adjust the empathic behavior depending on social and personal factors. Recent views posit, however, that the brain can be conceptualized as a complex system, in which behavior emerges from the interaction between functionally connected brain regions, organized into large-scale networks. Beyond the classical modular view of the brain, here we suggest that empathic behavior may be understood through a dynamic network-based approach where the cortical circuits associated with the experience of pain flexibly change in order to code self- and other related emotions and to intrinsically map our mentality to empathetically react to others. PMID- 26877106 TI - Inflammatory mediators in human epilepsy: A systematic review and meta-analysis. AB - BACKGROUND: Accumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy. METHODS: We performed a systematic review and meta analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis. RESULTS: 66 articles reporting on 1934 patients were included. IL-1ra, IL-1beta, IL-6, IL-10, IFN-gamma and TNF-alpha were the most extensively investigated proteins. Elevated levels for IL-1ra, IL 1beta, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL 1alpha, IL-7 and IL-13, as well as the chemokines CCL2-5, -19 and -22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1beta and IL-10. CONCLUSION: Inflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment. PMID- 26877107 TI - Social regulation of adult neurogenesis: A comparative approach. AB - The social environment sculpts the mammalian brain throughout life. Adult neurogenesis, the birth of new neurons in the mature brain, can be up- or down regulated by various social manipulations. These include social isolation, social conflict, social status, socio-sexual interactions, and parent/offspring interactions. However, socially-mediated changes in neuron production are often species-, sex-, and/or region-specific. In order to reconcile the variability of social effects on neurogenesis, we need to consider species-specific social adaptations and other contextual variables (e.g. age, social status, reproductive status, etc.) that shift the valence of social stimuli. Using a comparative approach to understand how adult-generated neurons in turn influence social behaviors will shed light on how adult neurogenesis contributes to survival and reproduction in diverse species. PMID- 26877108 TI - Leaf aging of Amazonian canopy trees as revealed by spectral and physiochemical measurements. AB - Leaf aging is a fundamental driver of changes in leaf traits, thereby regulating ecosystem processes and remotely sensed canopy dynamics. We explore leaf reflectance as a tool to monitor leaf age and develop a spectra-based partial least squares regression (PLSR) model to predict age using data from a phenological study of 1099 leaves from 12 lowland Amazonian canopy trees in southern Peru. Results demonstrated monotonic decreases in leaf water (LWC) and phosphorus (Pmass ) contents and an increase in leaf mass per unit area (LMA) with age across trees; leaf nitrogen (Nmass ) and carbon (Cmass ) contents showed monotonic but tree-specific age responses. We observed large age-related variation in leaf spectra across trees. A spectra-based model was more accurate in predicting leaf age (R2 = 0.86; percent root mean square error (%RMSE) = 33) compared with trait-based models using single (R2 = 0.07-0.73; %RMSE = 7-38) and multiple (R2 = 0.76; %RMSE = 28) predictors. Spectra- and trait-based models established a physiochemical basis for the spectral age model. Vegetation indices (VIs) including the normalized difference vegetation index (NDVI), enhanced vegetation index 2 (EVI2), normalized difference water index (NDWI) and photosynthetic reflectance index (PRI) were all age-dependent. This study highlights the importance of leaf age as a mediator of leaf traits, provides evidence of age-related leaf reflectance changes that have important impacts on VIs used to monitor canopy dynamics and productivity and proposes a new approach to predicting and monitoring leaf age with important implications for remote sensing. PMID- 26877109 TI - Molecular cloning and expression analysis on LPL of Coilia nasus. AB - Coilia nasus is one important commercial anadromous species which mainly distributed in the Yangtze River in China. At present, it has been on the "National Key Protective Species List" because of its severe resource damage. Lipid metabolism is very important during its long-distance migration. To make further research on lipid metabolism of C. nasus, we cloned lipoprotein lipase gene with homologous cloning method. A full-length cDNA of LPL of C. nasus was cloned from liver which covered 3537 bp with a 1519 bp open reading frame encoding 505 deduced amino acids whose molecular mass was 57.5 kDa and theoretical isoelectric point was 7.58. The deduced amino acids had high similarity with the reported LPL sequence of other species. It had typical conserved domain of LPL protein containing catalytic triad, N-linked glycosylation sites and conserved heparin-binding site, etc. We adopted quantitative real-time RT-PCR method to detect the mRNA expression of LPL of C. nasus in ten tissues including mesenteric adipose, liver, muscle, stomach, spleen, heart, head kidney, trunk kidney, gill and brain with beta-actin as internal reference. LPL expressed in all the detected tissues. The highest expression was in mesenteric adipose, and followed by liver, muscle, stomach. Lipid expressed lowly in spleen, heart, head kidney, trunk kidney, gill and brain. The research on the cloning and differential expression of LPL of C. nasus will lay foundation for further research on lipid metabolism of C. nasus. PMID- 26877110 TI - Characterization of an Apis cerana cerana cytochrome P450 gene (AccCYP336A1) and its roles in oxidative stresses responses. AB - Cytochrome P450 monooxygenases (P450), widely distributed multifunctional enzymes, that play an important role in the oxidative metabolism of endogenous compounds and xenobiotics. Studies have found that these enzymes show peroxidase like activity and may thus be involved in protecting organisms against reactive oxygen species (ROS). In this work, Apis cerana cerana was used to investigate the molecular mechanisms of P450 family genes in resisting ROS damage. A cytochrome P450 gene was isolated, AccCYP336A1. The open reading frame (ORF) of AccCYP336A1 is 1491bp in length and encodes a predicted protein of 496 amino acids. The obtained amino acid sequence of AccCYP336A1 shared a high sequence identity with homologous proteins and contained the highly conserved features of this protein family. Quantitative real-time PCR (qRT-PCR) analysis showed that AccCYP336A1 was present in some fast developmental stages and had a higher expression in the epidermis than in other tissues. Additionally, the expression levels of AccCYP336A1 were up-regulated by cold (4 degrees C), heat (42 degrees C), ultraviolet (UV) radiation, H2O2 and pesticide (thiamethoxam, deltamethrin, methomyl and phoxim) treatments. These results were confirmed by the western blot assays. Furthermore, the recombinant AccCYP336A1 protein acted as an antioxidant that resisted paraquat-induced oxidative stress. Taken together, these results suggest that AccCYP336A1 may play a very significant role in antioxidant defense against ROS damage. PMID- 26877111 TI - [Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care]. AB - BACKGROUND: In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. METHODS: This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. RESULTS: A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. CONCLUSIONS: The indication for anticoagulation is correct in our population, assuming a low intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient. PMID- 26877112 TI - Three-dimensional reconstruction of black tiger prawn (Penaeus monodon) spermatozoa using serial block-face scanning electron microscopy. AB - Serial Block-Face Scanning Electron Microscopy (SBF-SEM) was used in this study to examine the ultrastructural morphology of Penaeus monodon spermatozoa. SBF-SEM provided a large dataset of sequential electron-microscopic-level images that facilitated comprehensive ultrastructural observations and three-dimensional reconstructions of the sperm cell. Reconstruction divulged a nuclear region of the spermatophoral spermatozoon filled with decondensed chromatin but with two apparent levels of packaging density. In addition, the nuclear region contained, not only numerous filamentous chromatin elements with dense microregions, but also large centrally gathered granular masses. Analysis of the sperm cytoplasm revealed the presence of degenerated mitochondria and membrane-less dense granules. A large electron-lucent vesicle and "arch-like" structures were apparent in the subacrosomal area, and an acrosomal core was found in the acrosomal vesicle. The spermatozoal spike arose from the inner membrane of the acrosomal vesicle, which was slightly bulbous in the middle region of the acrosomal vesicle, but then extended distally into a broad dense plate and to a sharp point proximally. This study has demonstrated that SBF-SEM is a powerful technique for the 3D ultrastructural reconstruction of prawn spermatozoa, that will no doubt be informative for further studies of sperm assessment, reproductive pathology and the spermiocladistics of penaeid prawns, and other decapod crustaceans. PMID- 26877113 TI - Editorial Comment to Transvesical laparoscopic surgery for double renal pelvis and ureter with or without ureterocele. PMID- 26877114 TI - Reshaping clinical science: Introduction to the Special Issue on Psychophysiology and the NIMH Research Domain Criteria (RDoC) initiative. AB - The National Institute of Mental Health's (NIMH) Research Domain Criteria (RDoC) initiative seeks to establish new dimensional conceptions of mental health problems, through the investigation of clinically relevant "process" constructs that have neurobiological as well as psychological referents. This special issue provides a detailed overview of the RDoC framework by NIMH officials Michael Kozak and Bruce Cuthbert, and spotlights RDoC-oriented investigative efforts by leading psychophysiological research groups as examples of how clinical science might be reshaped through application of RDoC principles. Accompanying commentaries highlight key aspects of the work by each group, and discuss reported methods/findings in relation to promises and challenges of the RDoC initiative more broadly. PMID- 26877115 TI - The NIMH Research Domain Criteria Initiative: Background, Issues, and Pragmatics. AB - This article describes the National Institute of Mental Health's Research Domain Criteria (RDoC) initiative. The description includes background, rationale, goals, and the way the initiative has been developed and organized. The central RDoC concepts are summarized and the current matrix of constructs that have been vetted by workshops of extramural scientists is depicted. A number of theoretical and methodological issues that can arise in connection with the nature of RDoC constructs are highlighted: subjectivism and heterophenomenology, desynchrony and theoretical neutrality among units of analysis, theoretical reductionism, endophenotypes, biomarkers, neural circuits, construct "grain size," and analytic challenges. The importance of linking RDoC constructs to psychiatric clinical problems is discussed. Some pragmatics of incorporating RDoC concepts into applications for NIMH research funding are considered, including sampling design. PMID- 26877117 TI - Studies of auditory verbal hallucinations. AB - Neuroscientists have been exploring the mechanism of auditory verbal hallucinations. In this commentary, I review studies by Judy Ford, who employed a vocalization paradigm to test the hypothesis of impaired corollary discharge in psychotic patients who experience auditory verbal hallucinations. I highlight the strengths of this research program and reflect on the challenge of reducing a complex clinical feature to an abnormality of basic cognitive processes, such as language and memory. PMID- 26877116 TI - Studying auditory verbal hallucinations using the RDoC framework. AB - In this paper, I explain why I adopted a Research Domain Criteria (RDoC) approach to study the neurobiology of auditory verbal hallucinations (AVH), or voices. I explain that the RDoC construct of "agency" fits well with AVH phenomenology. To the extent that voices sound nonself, voice hearers lack a sense of agency over the voices. Using a vocalization paradigm like those used with nonhuman primates to study mechanisms subserving the sense of agency, we find that the auditory N1 ERP is suppressed during vocalization, that EEG synchrony preceding speech onset is related to N1 suppression, and that both are reduced in patients with schizophrenia. Reduced cortical suppression is also seen across multiple psychotic disorders and in clinically high-risk youth, but it is not related to AVH. The motor activity preceding talking and connectivity between frontal and temporal lobes during talking have both proved sensitive to AVH, suggesting neural activity and connectivity associated with intentions to act may be a better way to study agency and predictions based on agency. PMID- 26877118 TI - Achieving success with the Research Domain Criteria (RDoC): Going beyond the matrix. AB - Achieving Research Domain Criteria (RDoC) goals depends in part on how well scientists can grasp its principles and execute studies within its framework. Ford provides an exemplary illustration of a research program that aligns with RDoC guidelines. The future success of RDoC depends not just on research like that of Ford and colleagues. RDoC also must inspire the development of reliable neurobehavioral measures with demonstrable clinical validity that produce replicable findings leading to the establishment of neurocircuit-based behavioral dimensions that inform clinical work. Large samples not typically attainable in a clinical neuroscience laboratory or easily imagined within the confines of the RDoC matrix will be required if RDoC is to develop the insights and tools needed to establish incremental value over the DSM. Innovation that goes beyond reliance on the RDoC matrix and measures of neurocircuitry can help facilitate achievement of RDoC's goal of developing a science of psychopathology based on neurobiological systems. PMID- 26877119 TI - Panic disorder with agoraphobia from a behavioral neuroscience perspective: Applying the research principles formulated by the Research Domain Criteria (RDoC) initiative. AB - In the current review, we reconceptualize a categorical diagnosis-panic disorder and agoraphobia-in terms of two constructs within the domain "negative valence systems" suggested by the Research Domain Criteria initiative. Panic attacks are considered as abrupt and intense fear responses to acute threat arising from inside the body, while anxious apprehension refers to anxiety responses to potential harm and more distant or uncertain threat. Taking a dimensional view, panic disorder with agoraphobia is defined with the threat-imminence model stating that defensive responses are dynamically organized along the dimension of the proximity of the threat. We tested this model within a large group of patients with panic disorder and agoraphobia (N = 369 and N = 124 in a replication sample) and found evidence that panic attacks are indeed instances of circa strike defense. This component of the defensive reactivity was related to genetic modulators within the serotonergic system. In contrast, anxious apprehension-characterized by attentive freezing during postencounter defense-was related to general distress and depressive mood, as well as to genetic modulations within the hypothalamic-pituitary-adrenal (HPA) axis. Patients with a strong behavioral tendency for active and passive avoidance responded better to exposure treatment if the therapist guides the patient through the exposure exercises. PMID- 26877120 TI - Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience. AB - The Research Domain Criteria (RDoC) initiative endeavors to foster a science of psychopathology based around dimensions of brain-behavior relationships as opposed to subjectively based diagnostic categories. A rapidly accumulating array of transdiagnostic commonalities, across multiple objective and subjective measures, underscores the clear potential of this initiative. At the same time, a road map for guiding future RDoC research efforts is needed that draws upon the wealth of extant disorder-specific findings. In this issue, Hamm and colleagues provide an example of conceptualizing within-disorder processes in terms of dimensional brain-behavior relationships that advances the understanding of panic disorder with agoraphobia beyond the conventional nosological framework. Their findings and conceptual model are reviewed and discussed in terms of broader transdiagnostic implications. PMID- 26877121 TI - Taking an RDoC lens to the study of panic disorder: A commentary on Hamm et al. and other thoughts on RDoC. AB - The Research Domain Criteria (RDoC) initiative put forth by the National Institute of Mental Health represents an exciting new framework in which to study psychopathology. The article by Hamm et al. (2016) is an interesting application of an "RDoC lens" toward a program of research on panic disorder. This commentary highlights the many strengths of the Hamm et al. (2016) study-most notably the article's application of a well-studied animal model of anxiety (Fanselow's, , threat imminence model) to humans, utilization of an interesting behavioral paradigm (as an analog for avoidance behaviors in panic disorder), and using RDoC to examine predictors of treatment response. This commentary also discusses several questions about RDoC that arise out of Hamm et al. For example, (a) How should participants be selected for RDoC studies? (b) Are RDoC constructs risk factors (and risk factors for what)? (c) Besides Hamm et al.'s, approach, how else can RDoC be used in treatment studies? In sum, Hamm et al. is a very good example of an RDoC study, and in this early phase of the initiative, more examples for how the approach plays out are needed. PMID- 26877122 TI - Applying Research Domain Criteria (RDoC) to the study of fear and anxiety: A critical comment. AB - The goal of the Research Domain Criteria (RDoC) is to develop an interdisciplinary science of psychopathology, forming a template for research and disconnecting conceptual and empirical questions from traditional diagnostic entities. In this article, we review some of the challenges in the implementation of this framework within the field of pathological fear and anxiety, specifically commenting on the article by Hamm and colleagues (2016). The study of pathological fear and anxiety has had considerable, yet stalled, success in its understanding of underlying mechanisms, prevention, and treatment. With a shift toward RDoC, it is unclear what to do with the existing diagnostic labels, and the importance of defining and measuring phenotypes becomes paramount. Additional concerns include the role of psychological constructs and mechanisms, the use of self-report measures, the examination of replication and clinical utility, and the measurement of the role of the environment. Though a laudable and potentially necessary shift in focus, it remains to be seen whether new overall insights into psychopathology will emerge from focusing on small units of analyses and piecing them together and whether these insights will directly translate into the prevention of psychopathology, more efficacious treatments, and improved lives of patients. PMID- 26877124 TI - Psychophysiology of threat response, paradigm shifts in psychiatry, and RDoC: Implications for genetic investigation of psychopathology. AB - Two articles in this issue seek to further the goal of NIMH's Research Domain Criteria (RDoC) initiative to develop new approaches for investigating mental disorders, using fundamental dimensions that cut across traditional disorder categories and align more closely with mechanisms that underlie psychopathology. One article, by Lang, McTeague, and Bradley, describes the construction of such a disorder cross-crossing dimension of fear response. The other, by Kozak and Cuthbert, expounds upon the basis and conceptualization of research targets under RDoC. Possible implications of these developments for psychiatric genetics research are discussed. PMID- 26877123 TI - RDoC, DSM, and the reflex physiology of fear: A biodimensional analysis of the anxiety disorders spectrum. AB - Evidence is presented supporting a dimension of defensive reactivity that varies across the anxiety disorder spectrum and is defined by physiological responses during threat-imagery challenges that covary with objective measures of psychopathology. Previous imagery studies of anxiety disorders are reviewed, highlighting that, regardless of contemporary diagnostic convention, reliable psychophysiological patterns emerge for patients diagnosed with circumscribed fear compared to those diagnosed with pervasive anxious-misery disorders. Based on the heuristic outlined by the Research Domain Criteria (RDoC) initiative, an exploratory transdiagnostic analysis is presented, based on a sample of 425 treatment-seeking patients from across the spectrum of DSM-IV anxiety diagnoses. Using a composite index of startle reflex and heart rate reactivity during idiographic fear imagery for each patient, a defensive dimension was defined by ranking patients from most defensively reactive to least reactive and then creating five groups of equivalent size (quintile; N = 85). Subsequent analyses showed significant parallel trends of diminishing reactivity in both electrodermal and facial electromyographic reactions across this defensive dimension. Negative affectivity, defined by questionnaire and extent of functional interference, however, showed consistent, inverse trends with defensive reactivity-as reports of distress increased, defensive reactivity was increasingly attenuated. Notably, representatives of each principal diagnosis appeared in each quintile, underscoring the reality of pronounced within diagnosis heterogeneity in defensive reactivity. In concluding, we describe our new RDoC research project, focusing on the assessment of brain circuit function as it determines hypo/hyperreactivity to challenge-somatic and autonomic-and may relate to patients' stress history and genetic inheritance. PMID- 26877125 TI - The RDoC initiative and the structure of psychopathology. AB - The NIMH Research Domain Criteria (RDoC) project represents a welcome effort to circumvent the limitations of psychiatric categories as phenotypes for psychopathology research. Here, we describe the hierarchical and dimensional structure of phenotypic psychopathology and illustrate how this structure provides phenotypes suitable for RDoC research on neural correlates of psychopathology. A hierarchical and dimensional approach to psychopathology phenotypes holds great promise for delineating connections between neuroscience constructs and the patterns of affect, cognition, and behavior that constitute manifest psychopathology. PMID- 26877126 TI - Displacement behaviors in chimpanzees (Pan troglodytes): A neurogenomics investigation of the RDoC Negative Valence Systems domain. AB - The current study aimed to systematically investigate genetic and neuroanatomical correlates of individual variation in scratching behaviors, a well-validated animal-behavioral indicator of negative emotional states with clear links to the NIMH Research Domain Criteria (RDoC) response to potential harm ("anxiety") construct within the Negative Valence Systems domain. Utilizing data from a sample of 76 captive chimpanzees (Pan troglodytes), we (a) examined the association between scratching and presence or absence of the RS3-containing DupB element in the AVPR1A 5' flanking region, (b) utilized voxel-based morphometry (VBM) to identify gray matter (GM) voxel clusters that differentiated AVPR1A genotype, and (c) conducted a VBM-guided voxel-of-interest analysis to examine the association between GM intensity and scratching. AVPR1A evidenced sexually dimorphic associations with scratching. VBM analyses revealed significant differences in GM by genotype across twelve clusters largely in the frontal cortex. Regions differentiating AVPR1A genotype showed sex-specific associations with scratching. Results suggest that sexually dimorphic associations between AVPR1A and scratching may be explained by genotype-specific neuroanatomical variation. The current study provides an example of the way in which chimpanzee research is uniquely poised for multilevel, systematic investigations of psychopathology-relevant constructs within the context of the RDoC framework. PMID- 26877127 TI - Neuroethology as a translational neuroscience strategy in the era of the NIMH Research Domain Criteria. AB - The article by Latzman et al. in the current special issue utilizes a novel dataset consisting of behavioral, brain, and genomic data from a sample of 76 captive chimpanzees to make the case that negative affective expression is influenced by variation in the gene coding for arginine vasopressin receptor 1A (AVPR1A), in a sex-linked manner. A novel feature of this study is the ethological approach employed by the authors, i.e., the use of scratching as a behavioral indicator of negative affective state. I comment on conceptual and methodological aspects of this work, and consider how it interfaces with the Research Domain Criteria (RDoC) framework as described by Kozak and Cuthbert in their article for this issue. PMID- 26877128 TI - Using the NIMH Research Domain Criteria (RDoC) in human and nonhuman primate research. AB - In this article, we provide a commentary on Kozak and Cuthbert ()'s theoretical paper discussing the NIMH Research Domain Criteria (RDoC) initiative and on Latzman et al. (2016)'s empirical investigation of the RDoC negative valence systems domain in chimpanzees, conducted with experimental procedures across genetic, neurobiological, and behavioral levels of analysis. We discuss the pros and cons of the RDoC approach to research on mental illness as well as the strengths and weaknesses of the implementation of this approach in the chimpanzee study. PMID- 26877130 TI - The NIMH Research Domain Criteria initiative and error-related brain activity. AB - Research on the neural response to errors has an important role in the Research Domain Criteria (RDoC) project, since it is likely to link psychopathology to the dysfunction of neural systems underlying basic behavioral functions, with the error-related negativity (ERN) appearing as a unit of measurement in three RDoC domains. A recent report builds on previous research by examining the ERN as a measure of the sustained threat construct and providing evidence that the ERN may reflect sensitivity more specifically to endogenous threat. Data from 515 adolescent females indicate that the ERN was enlarged primarily in older adolescents with self-reported checking behaviors, although it was blunted in adolescents with depressive symptoms regardless of age. Potential future studies for replicating and extending the research on the ERN and obsessive-compulsive (OC) behaviors are discussed, including studies that more fully characterize OC symptom dimensions, studies that integrate other measures of error-related brain activity and use computational modeling, studies that combine longitudinal, family, and molecular genetic measures, and interventional studies that specifically modulate error-related brain activity in individuals with OC behaviors. PMID- 26877131 TI - The error-related negativity: A transdiagnostic marker of sustained threat? AB - The creation of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) project has been the driving force behind the reconceptualization of the pathogenesis of psychiatric disorders. In this commentary, I explore whether the error-related negativity can be considered as a transdiagnostic marker of sustained threat based on findings from Weinberg, Meyer et al.'s (2016) study in relation to current findings in the literature. Potential alternative study designs, use of a multimodal approach to the assessment of a specific phenotype of clinical phenomenon, and the importance of integrating a neurodevelopmental perspective are also discussed. PMID- 26877129 TI - Error-related negativity (ERN) and sustained threat: Conceptual framework and empirical evaluation in an adolescent sample. AB - The error-related negativity (ERN) currently appears as a physiological measure in relation to three Research Domain Criteria (RDoC) constructs: Cognitive Control, Sustained Threat, and Reward Learning. We propose a conceptual model in which variance in the ERN reflects individual differences in the degree to which errors are evaluated as threatening. We also discuss evidence for the placement of the ERN in the "Sustained Threat" construct, as well as evidence that the ERN may more specifically reflect sensitivity to endogenous threat. Following this, we present data from a sample of 515 adolescent females demonstrating a larger ERN in relation to self-reported checking behaviors, but only in older adolescents, suggesting that sensitivity to internal threat and the ERN-checking relationship may follow a developmental course as adolescents develop behavioral control. In contrast, depressive symptoms were linked to a smaller ERN, and this association was invariant with respect to age. Collectively, these data suggest that the magnitude of the ERN is sensitive both to specific anxiety-related processes and depression, in opposing directions that may reflect variation in internal threat sensitivity. We discuss directions for future research, as well as ways in which findings for the ERN complement and challenge aspects of the current RDoC matrix. PMID- 26877132 TI - Psychoneurometric operationalization of threat sensitivity: Relations with clinical symptom and physiological response criteria. AB - The National Institute of Mental Health's Research Domain Criteria (RDoC) initiative calls for the incorporation of neurobiological approaches and findings into conceptions of mental health problems through a focus on biobehavioral constructs investigated across multiple domains of measurement (units of analysis). Although the constructs in the RDoC system are characterized in "process terms" (i.e., as functional concepts with brain and behavioral referents), these constructs can also be framed as dispositions (i.e., as dimensions of variation in biobehavioral functioning across individuals). Focusing on one key RDoC construct, acute threat or "fear," the current article illustrates a construct-oriented psychoneurometric strategy for operationalizing this construct in individual difference terms-as threat sensitivity (THT+). Utilizing data from 454 adult participants, we demonstrate empirically that (a) a scale measure of THT+ designed to tap general fear/fearlessness predicts effectively to relevant clinical problems (i.e., fear disorder symptoms), (b) this scale measure shows reliable associations with physiological indices of acute reactivity to aversive visual stimuli, and (c) a cross-domain factor reflecting the intersection of scale and physiological indicators of THT+ predicts effectively to both clinical and neurophysiological criterion measures. Results illustrate how the psychoneurometric approach can be used to create a dimensional index of a biobehavioral trait construct, in this case THT+, which can serve as a bridge between phenomena in domains of psychopathology and neurobiology. Implications and future directions are discussed with reference to the RDoC initiative and existing report-based conceptions of psychological traits. PMID- 26877135 TI - RDoC: Translating promise into progress. AB - As highlighted by articles in the current special issue, the RDoC initiative holds promise for advancing understanding of mental health problems. However, the initiative is at its early stages and it remains unclear what level of progress can be achieved and how quickly. In this closing article, we identify major challenges facing RDoC and propose concrete approaches to addressing these challenges, including (a) clearer specification of clinical problems for study, with use of symptom dimensions from integrative dimensional models of psychopathology as provisional, modifiable referents; (b) encouragement of research on a distinct set of traits corresponding to process constructs from the RDoC matrix-those represented across animal, child temperament, and adult personality literatures-to serve as interfaces between matrix constructs and clinical problems; (c) an emphasis in the near term on use of proximal units of analysis in RDoC studies-in particular, on physiological, behavioral, and self report measures of matrix constructs (examined as states or traits, or both); (d) inclusion of a clear ontogenetic-developmental component in RDoC research projects; (e) routine analysis of the psychometric properties of nonreport (e.g., physiological, task-behavioral) variables, including systematic evaluation of their reliability and convergent-discriminant validity; (f) modification of existing grant review criteria to prioritize replication and synergy in RDoC investigative work; and (g) creation of a cumulative data network system (RDoC DataWeb) to encourage and facilitate coordination of research efforts across RDoC research groups. PMID- 26877133 TI - Psychobiological operationalization of RDoC constructs: Methodological and conceptual opportunities and challenges. AB - NIMH's Research Domain Criteria (RDoC) project seeks to advance the diagnosis, prevention, and treatment of mental disorders by promoting psychobiological research on dimensional constructs that might cut across traditional diagnostic boundaries (Kozak & Cuthbert, ). At the core of this approach is the notion that these dimensional constructs can be assessed across different units of analysis (e.g., genes, physiology, behavior), enriching the constructs and providing more complete explanations of clinical problems. While the conceptual aspects of RDoC have been discussed in several prior papers, its methodological aspects have received comparatively less attention. For example, how to integrate data from different units of analysis has been relatively unclear. Here, we discuss one means of psychobiologically operationalizing RDoC constructs across different units of analysis (the psychoneurometric approach; Yancey et al., ), highlighting ways in which this approach might be refined in future iterations. We conclude that there is much to be learned from this technique; however, greater attention to scale-development methods and to psychometrics will likely benefit this and other methodological approaches to combining measurements across multiple units of analysis. PMID- 26877134 TI - Psychophysiology as a core strategy in RDoC. AB - The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health shows great promise in providing guidance for research on mental illness but has prompted considerable controversy. Papers by Yancey, Venables, and Patrick and Kozak and Cuthbert illustrate and clarify a number of important features of RDoC. The present commentary evaluates the former paper in light of the latter paper and addresses several common misunderstandings about RDoC. The concept of endophenotypes and diverse psychophysiological approaches will likely be central in RDoC-inspired research. PMID- 26877136 TI - FLDS: A Comprehensive dsRNA Sequencing Method for Intracellular RNA Virus Surveillance. AB - Knowledge of the distribution and diversity of RNA viruses is still limited in spite of their possible environmental and epidemiological impacts because RNA virus-specific metagenomic methods have not yet been developed. We herein constructed an effective metagenomic method for RNA viruses by targeting long double-stranded (ds)RNA in cellular organisms, which is a hallmark of infection, or the replication of dsRNA and single-stranded (ss)RNA viruses, except for retroviruses. This novel dsRNA targeting metagenomic method is characterized by an extremely high recovery rate of viral RNA sequences, the retrieval of terminal sequences, and uniform read coverage, which has not previously been reported in other metagenomic methods targeting RNA viruses. This method revealed a previously unidentified viral RNA diversity of more than 20 complete RNA viral genomes including dsRNA and ssRNA viruses associated with an environmental diatom colony. Our approach will be a powerful tool for cataloging RNA viruses associated with organisms of interest. PMID- 26877137 TI - Temperature-Dependent Expression of NodC and Community Structure of Soybean Nodulating Bradyrhizobia. AB - In order to assess the physiological responses of bradyrhizobia and competition for the nodulation of soybean at different temperatures, we investigated the expression of the nodC gene at 20, 25, and 30 degrees C and the abilities of bacteria to nodulate soybean in microcosms at day/night cultivation temperatures of 23/18 degrees C, 28/23 degrees C, and 33/28 degrees C for 16/8 h. We tested five Bradyrhizobium USDA strains: B. diazoefficiens USDA 110(T) and 122, B. japonicum USDA 123, and B. elkanii USDA 31 and 76(T). The expression of nodC was up-regulated by increasing culture temperatures in USDA 110(T), 122, 31, and 76(T), but was down-regulated in USDA 123. The proportions of USDA 110(T) and 122 within the community were the greatest at 28/23 degrees C. The population of USDA 31 increased, whereas that of USDA 123 decreased with increasing cultivation temperatures. On the other hand, infection by USDA 76(T) was not detected, and low numbers of USDA 76(T) nodules confirmed its poor nodulation ability. These results indicate that the competitiveness of and infection by USDA 110(T), 122, 123, and 31 for soybean nodulation depend on cultivation temperatures, and suggest that the temperature dependence of nodC expression affects the bradyrhizobial community structure. PMID- 26877139 TI - Mechanisms of pulmonary cyst pathogenesis in Birt-Hogg-Dube syndrome: The stretch hypothesis. AB - Loss-of-function mutations in the folliculin gene (FLCN) on chromosome 17p cause Birt-Hogg-Dube syndrome (BHD), which is associated with cystic lung disease. The risk of lung collapse (pneumothorax) in BHD patients is 50-fold higher than in the general population. The cystic lung disease in BHD is distinctive because the cysts tend to be basilar, subpleural and lentiform, differentiating BHD from most other cystic lung diseases. Recently, major advances in elucidating the primary functions of the folliculin protein have been made, including roles in mTOR and AMPK signaling via the interaction of FLCN with FNIP1/2, and cell-cell adhesion via the physical interaction of FLCN with plakophilin 4 (PKP4), an armadillo repeat containing protein that interacts with E-cadherin and is a component of the adherens junctions. In addition, in just the last three years, the pulmonary impact of FLCN deficiency has been examined for the first time. In mouse models, evidence has emerged that AMPK signaling and cell-cell adhesion are involved in alveolar enlargement. In addition, the pathologic features of human BHD cysts have been recently comprehensively characterized. The "stretch hypothesis" proposes that cysts in BHD arise because of fundamental defects in cell-cell adhesion, leading to repeated respiration-induced physical stretch-induced stress and, over time, expansion of alveolar spaces particularly in regions of the lung with larger changes in alveolar volume and at weaker "anchor points" to the pleura. This hypothesis ties together many of the new data from cellular and mouse models of BHD and from the human pathologic studies. Critical questions remain. These include whether the consequences of stretch-induced cyst formation arise through a destructive/inflammatory program or a proliferative program (or both), whether cyst initiation involves a "second hit" genetic event inactivating the remaining wild-type copy of FLCN (as is known to occur in BHD-associated renal cell carcinomas), and whether cyst initiation involves exclusively the epithelial compartment versus an interaction between the epithelium and mesenchyme. Ultimately, understanding the mechanisms of cystic lung disease in BHD may help to elucidate the pathogenesis of primary spontaneous pneumothorax, with more than 20,000 cases reported annually in the United States alone. PMID- 26877138 TI - Sordaria, a model system to uncover links between meiotic pairing and recombination. AB - The mycelial fungus Sordaria macrospora was first used as experimental system for meiotic recombination. This review shows that it provides also a powerful cytological system for dissecting chromosome dynamics in wild-type and mutant meioses. Fundamental cytogenetic findings include: (1) the identification of presynaptic alignment as a key step in pairing of homologous chromosomes. (2) The discovery that biochemical complexes that mediate recombination at the DNA level concomitantly mediate pairing of homologs. (3) This pairing process involves not only resolution but also avoidance of chromosomal entanglements and the resolution system includes dissolution of constraining DNA recombination interactions, achieved by a unique role of Mlh1. (4) Discovery that the central components of the synaptonemal complex directly mediate the re-localization of the recombination proteins from on-axis to in-between homologue axis positions. (5) Identification of putative STUbL protein Hei10 as a structure-based signal transduction molecule that coordinates progression and differentiation of recombinational interactions at multiple stages. (6) Discovery that a single interference process mediates both nucleation of the SC and designation of crossover sites, thereby ensuring even spacing of both features. (7) Discovery of local modulation of sister-chromatid cohesion at sites of crossover recombination. PMID- 26877140 TI - Energy sensing and cancer: LKB1 function and lessons learnt from Peutz-Jeghers syndrome. AB - We describe in this review increasing evidence that loss of LKB1 kinase in Peutz Jeghers syndrome (PJS) derails the existing natural balance between cell survival and tumour growth suppression. LKB1 deletion can plunge cells into an energy/oxidative stress-induced crisis which leads to the activation of alternative and often carcinogenic pathways to maintain cellular energy levels. It therefore appears that although LKB1 deficiency can suppress oncogenic transformation in the short term, it can ultimately lead to more progressed and malignant phenotypes by driving abnormal cell differentiation, genomic instability and increased tumour heterogeneity. PMID- 26877141 TI - Making the invisible visible. AB - In this review, I will discuss how careful scrutiny of genetic skin disorders could help us to understand human biology. Like other organs, the skin and its appendages, such as hairs and teeth, experience fundamental biological processes ranging from lipid metabolism to vesicular transport and cellular migration. However, in contrast to other organ systems, they are accessible and can be studied with relative ease. By visually revealing the functional consequences of single gene defects, genetic skin diseases offer a unique opportunity to study human biology. Here, I will illustrate this concept by discussing how human genetic disorders of skin pigmentation reflect the mechanisms underlying this complex and vital process. PMID- 26877142 TI - Nosocomial infection and its molecular mechanisms of antibiotic resistance. AB - Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum beta-lactamases, (ii) AmpC beta-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized. PMID- 26877143 TI - Effects of Cocoa Husk Feeding on the Composition of Swine Intestinal Microbiota. AB - A two-diet/two-period change over experiment was performed to investigate the effects of cocoa husks, as a source of dietary fiber and polyphenols, on pig intestinal microbial composition. Six pigs were fed a conventional cereal-based diet or a diet obtained by substitution of 7.5% of the conventional diet with cocoa husks for 3 weeks. Experimental diets were isoproteic and isoenergetic. At the end of each 3 week testing period, samples of fresh feces were collected and analyzed for microbial composition by fluorescence in situ hybridization. Cocoa husks did not affect feed intake, weight gain, and feed efficiency. Analysis of fecal microbial populations, grouped by phyla, showed a decrease of Firmicutes and an increase of Bacteroidetes in cocoa husk-fed pigs. Particularly, cocoa husks reduced fecal populations of the Lactobacillus-Enterococcus group and Clostridium histolyticum and increased the Bacteroides-Prevotella group and Faecalibacterium prausnitzii, suggesting a potential for cocoa husks in the improvement of intestinal microbial balance. PMID- 26877144 TI - Assembly of coupled redox fuel cells using copper as electron acceptors to generate power and its in-situ retrieval. AB - Energy extraction from waste has attracted much interest nowadays. Herein, a coupled redox fuel cell (CRFC) device using heavy metals, such as copper, as an electron acceptor is assembled to testify the recoveries of both electricity and the precious metal without energy consumption. In this study, a NaBH4-Cu(II) CRFC was employed as an example to retrieve copper from a dilute solution with self electricity production. The properties of the CRFC have been characterized, and the open circuit voltage was 1.65 V with a maximum power density of 7.2 W m(-2) at an initial Cu(2+) concentration of 1,600 mg L(-1) in the catholyte. 99.9% of the 400 mg L(-1) copper was harvested after operation for 24 h, and the product formed on the cathode was identified as elemental copper. The CRFC demonstrated that useful chemicals were recovered and the electricity contained in the chemicals was produced in a self-powered retrieval process. PMID- 26877145 TI - Ultrasound-mediated modulation of the emission of gold nanodots. AB - In this study, we employed ultrasound-based treatment to mediate the emission properties of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide-capped gold nanodots (11-MUTAB-Au NDs). The as-prepared 11-MUTAB-Au NDs (sizes: ca. 1.8 nm), obtained from the reaction of gold nanoparticles (ca. 3 nm) and 11-MUTAB, exhibited very weak red photoluminescence (PL) near 670 nm [quantum yield (QY): 0.01%] upon excitation at 365 nm. After ultrasonication (20 W) for 2 h, however, the 11-MUTAB-Au NDs exhibited a >1000-fold enhancement in their PL intensity (QY: 11.5%), which shifted to a green color (ca. 540 nm) with a longer PL lifetime, due to the smaller size of the resulting NDs and the higher density of their capping 11-MUTAB ligands. Moreover, the PL of the 11-MUTAB-Au NDs returned to the near-infrared region (ca. 810 nm) after ultrasonication for a long period of time (>5 h). The dramatically different optical properties of these alkanethiol protected Au NDs after ultrasonication were presumably due to variation in their ligand densities; these effects were highly regulated by varying the ultrasonication time and power. Because the size, oxidation state, surface ligand density, and PL of these Au NDs could be controlled simply through ultrasonic treatment, this approach might open up new avenues for the preparation of emission-tunable metallic (e.g., Au, Ag, Pt) NDs presenting various capping ligands. PMID- 26877146 TI - Big Five Personality Traits and the General Factor of Personality as Moderators of Stress and Coping Reactions Following an Emergency Alarm on a Swiss University Campus. AB - We conducted an online survey including 306 participants aged 18-64 years to assess the general factor of personality (GFP) and Big Five personality traits in relation to individual stress and coping reactions following a shooting emergency alarm at a Swiss university campus. Although the emergency eventually turned out to be a false alarm, various witnesses showed pronounced distress owing to a vast police operation. The GFP structure was replicated using two alternative modelling approaches. Neuroticism related substantially to acute fear and traumatic distress as well as to more enduring maladaptive coping. Agreeableness was negatively associated with the coping strategy of medication use, whereas both agreeableness and conscientiousness related positively to social activity following the emergency. The GFP related moderately to peri-traumatic distress and showed a substantial negative association with medication use and a strong positive association with social activity. In conclusion, both the GFP and Big Five traits significantly moderate stress responses following a stressful life event. The GFP predominantly relates to socially adaptive coping, whereas in particular neuroticism accounts for acute stress reactions such as fear and traumatic distress. These findings support the notion that personality influences how persons react in the face of adversity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26877147 TI - An experimental 'Life' for an experimental life: Richard Waller's biography of Robert Hooke (1705). AB - Richard Waller's 'Life of Dr Robert Hooke', prefixed to his edition of Hooke's Posthumous Works (1705), is an important source for the life of one of the most eminent members of the early Royal Society. It also has the distinction of being one of the earliest biographies of a man of science to be published in English. I argue that it is in fact the first biography to embrace the subject's natural philosophical work as the centre of his life, and I investigate Waller's reasons for adopting this strategy and his struggle with the problem of how to represent an early experimental philosopher in print. I suggest that Waller eschews the 'Christian philosopher' tradition of contemporary biography - partly because of the unusually diverse and fragmentary nature of Hooke's intellectual output - and draws instead upon the structure of the Royal Society's archive as a means of organizing and understanding Hooke's life. The most quoted phrase from Waller's biography is that Hooke became 'to a crime close and reserved' in later life; this essay argues that Waller's biographical sketch was fashioned in order to undo the effects of that reserve. In modelling his approach very closely on the structure of the society's records he was principally concerned with making Hooke's work and biography accessible, intelligible and useful to the fellowship in a context familiar to them, a context which had provided the institutional framework for most of Hooke's adult life. I argue that Waller's 'Life' was also intended to make the largest claims for Hooke's intellectual standing that the author dared in the context of the enmity between Hooke and Isaac Newton once the latter became president of the Royal Society. However, I also adduce fresh manuscript evidence that Waller actually compiled, but did not publish, a defence of Hooke's claim to have discovered the inverse square law of gravity, allowing us to glimpse a much more assertive biography of Hooke than the published version. PMID- 26877148 TI - Involvement of an octose ketoreductase and two acyltransferases in the biosynthesis of paulomycins. AB - C-4 hydroxyethyl branched octoses have been observed in polysaccharides of several genera of gram negative bacteria and in various antibiotics produced by gram positive bacteria. The C-4 hydroxyethyl branch was proposed to be converted from C-4 acetyl branch by an uncharacterized ketoreduction step. Paulomycins (PAUs) are glycosylated antibiotics with potent inhibitory activity against gram positive bacteria and are structurally defined by its unique C-4' hydroxyethyl branched paulomycose moiety. A novel aldo-keto-reductase, Pau7 was characterized as the enzyme catalyzing the stereospecific ketoreduction of 7'-keto of PAU E (1) to give the C-4' hydroxyethyl branched paulomycose moiety of PAU F (2). An acyltransferase Pau6 further decorates the C-4' hydroxyethyl branch of paulomycose moiety of 2 by attaching various fatty acyl chains to 7'-OH to generate diverse PAUs. In addition, another acyltransferase Pau24 was proposed to be responsible for the 13-O-acetylation of PAUs. PMID- 26877149 TI - Genome wide transcriptome profiling reveals differential gene expression in secondary metabolite pathway of Cymbopogon winterianus. AB - Advances in transcriptome sequencing provide fast, cost-effective and reliable approach to generate large expression datasets especially suitable for non-model species to identify putative genes, key pathway and regulatory mechanism. Citronella (Cymbopogon winterianus) is an aromatic medicinal grass used for anti tumoral, antibacterial, anti-fungal, antiviral, detoxifying and natural insect repellent properties. Despite of having number of utilities, the genes involved in terpenes biosynthetic pathway is not yet clearly elucidated. The present study is a pioneering attempt to generate an exhaustive molecular information of secondary metabolite pathway and to increase genomic resources in Citronella. Using high-throughput RNA-Seq technology, root and leaf transcriptome was analysed at an unprecedented depth (11.7 Gb). Targeted searches identified majority of the genes associated with metabolic pathway and other natural product pathway viz. antibiotics synthesis along with many novel genes. Terpenoid biosynthesis genes comparative expression results were validated for 15 unigenes by RT-PCR and qRT-PCR. Thus the coverage of these transcriptome is comprehensive enough to discover all known genes of major metabolic pathways. This transcriptome dataset can serve as important public information for gene expression, genomics and function genomics studies in Citronella and shall act as a benchmark for future improvement of the crop. PMID- 26877150 TI - Mining the genome of Rhodococcus fascians, a plant growth-promoting bacterium gone astray. AB - Rhodococcus fascians is a phytopathogenic Gram-positive Actinomycete with a very broad host range encompassing especially dicotyledonous herbaceous perennials, but also some monocots, such as the Liliaceae and, recently, the woody crop pistachio. The pathogenicity of R. fascians strain D188 is known to be encoded by the linear plasmid pFiD188 and to be dictated by its capacity to produce a mixture of cytokinins. Here, we show that D188-5, the nonpathogenic plasmid-free derivative of the wild-type strain D188 actually has a plant growth-promoting effect. With the availability of the genome sequence of R. fascians, the chromosome of strain D188 was mined for putative plant growth-promoting functions and the functionality of some of these activities was tested. This analysis together with previous results suggests that the plant growth-promoting activity of R. fascians is due to production of plant growth modulators, such as auxin and cytokinin, combined with degradation of ethylene through 1-amino-cyclopropane-1 carboxylic acid deaminase. Moreover, R. fascians has several functions that could contribute to efficient colonization and competitiveness, but there is little evidence for a strong impact on plant nutrition. Possibly, the plant growth promotion encoded by the D188 chromosome is imperative for the epiphytic phase of the life cycle of R. fascians and prepares the plant to host the bacteria, thus ensuring proper continuation into the pathogenic phase. PMID- 26877151 TI - Whole transcriptome analysis of transgenic barley with altered cytokinin homeostasis and increased tolerance to drought stress. AB - Cytokinin plant hormones have been shown to play an important role in plant response to abiotic stresses. Herein, we expand upon the findings of Pospisilova et al. [30] regarding preparation of novel transgenic barley lines overexpressing cytokinin dehydrogenase 1 gene from Arabidopsis under the control of mild root specific promotor of maize beta-glycosidase. These lines showed drought-tolerant phenotype mainly due to alteration of root architecture and stronger lignification of root tissue. A detailed transcriptomic analysis of roots of transgenic plants subjected to revitalization after drought stress revealed attenuated response through the HvHK3 cytokinin receptor and up-regulation of two transcription factors implicated in stress responses and abscisic acid sensitivity. Increased expression of several genes involved in the phenylpropanoid pathway as well as of genes encoding arogenate dehydratase/lyase participating in phenylalanine synthesis was found in roots during revitalization. Although more precursors of lignin synthesis were present in roots after drought stress, final lignin accumulation did not change compared to that in plants grown under optimal conditions. Changes in transcriptome indicated a higher auxin turnover in transgenic roots. The same analysis in leaves revealed that genes encoding putative enzymes responsible for production of jasmonates and other volatile compounds were up-regulated. Although transgenic barley leaves showed lower chlorophyll content and down-regulation of genes encoding proteins involved in photosynthesis than did wild-type plants when cultivated under optimal conditions, they did show a tendency to return to initial photochemical activities faster than did wild-type leaves when re-watered after severe drought stress. In contrast to optimal conditions, comparative transcriptomic analysis of revitalized leaves displayed up-regulation of genes encoding enzymes and proteins involved in photosynthesis, and especially those encoded by the chloroplast genome. Taken together, our results indicate that the partial cytokinin insensitivity induced in barley overexpressing cytokinin dehydrogenase contributes to tolerance to drought stress. PMID- 26877152 TI - Chalcogen bonding interactions between reducible sulfur and selenium compounds and models of zinc finger proteins. AB - Reducible sulfur and selenium (r-S/Se) compounds, defined as sulfur and selenium compounds not in the lowest -2 oxidation state (e.g., -1 to +6), release Zn(2+) from zinc-sulfur proteins such as zinc fingers (ZFs) and metallothionein. A series of density functional theory calculations was performed on donor-acceptor complexes between r-S/Se compounds and models of the Cys2His2, Cys3His and Cys4 ZF sites. These S?S/Se chalcogen bonding interactions consist of the donation of electron density from a S lone pair on the ZF model to a S/Se-X antibonding molecular orbital of the r-S/Se compound. The strength of the interaction was shown to be dependent upon the Lewis basicity of the ZF model (Cys4>Cys3His>Cys2His2) and the Lewis acidity of the r-S/Se compound as measured by the energy of the S/Se-X antibonding orbital. Interactions with the softer r Se compounds were stronger than the r-S compounds, consistent with the greater reactivity of the former with ZF proteins. PMID- 26877153 TI - Does allostatic load calculation method matter? Evaluation of different methods and individual biomarkers functioning by race/ethnicity and educational level. AB - OBJECTIVES: Using nationally representative data for adults of age 25 years and older from four waves of the National Health and Nutrition Examination Survey (NHANES), collected from 2003 through 2010, this study examines differences in individual health markers used to calculate allostatic load, with particular attention given to stratification by race/ethnicity and educational level. METHODS: Factor analysis with maximum likelihood estimation was used. Fisher's r to z transformation test was used to determine whether or not observed differences in factor loadings were statistically significant. RESULTS: The findings reveal the unidimensionality of the concept of allostatic load and the underlying differences in associations between individual biomarkers and summary measures of allostatic load. Additionally, metabolic processes tend to be the most important predictor of allostatic load for all adults; however, inflammatory measures are more important in determining allostatic load scores for non Hispanic blacks compared to non-Hispanic whites and for adults with less than a college education compared to adults with some college or a college degree. CONCLUSIONS: These findings highlight the continued importance of studying the concept of "weathering" or allostatic load at the population level and need to better understand how population groups facing exclusion from economic, social, and political power may internalize this position which may cause early health deterioration and ultimate mortality chance through different expression of health insults and premature aging. Am. J. Hum. Biol. 28:627-635, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26877154 TI - Cyclosporine A lipid nanoparticles for oral administration: Pharmacodynamics and safety evaluation. AB - The pharmacodynamic effect and the safety of cyclosporine A lipid nanoparticles (CsA LN) for oral administration were investigated using Sandimmune Neoral(r) as reference. First, the biocompatibility of the unloaded LN on Caco-2 cells was demonstrated. The pharmacodynamic response and blood levels of CsA were studied in Balb/c mice after 5 and 10 days of daily oral administration equivalent to 5 and 15 mg/kg of CsA in different formulations. The in vivo nephrotoxicity after 15 days of treatment at the high dose was also evaluated. The results showed a significant decrease in lymphocyte count (indicator of immunosuppression) for the CsA LN groups which was not observed with Sandimmune Neoral(r). CsA blood levels remained constant over the time after treatment with LN, whereas a proportional increase in drug blood concentration was observed with Sandimmune Neoral(r). Therefore, CsA LN exhibited a better pharmacological response along with more predictable pharmacokinetic information, diminishing the risk of toxicity. Moreover, a nephroprotective effect against CsA related toxicity was observed in the histopathological evaluation when LN containing Tween(r) 80 were administered. Therefore, our preliminary findings suggest LN formulations would be a good alternative for CsA oral delivery, enhancing efficacy and reducing the risk of nephrotoxicity. PMID- 26877156 TI - Tissue engineering advances in spine surgery. AB - Autograft, while currently the gold standard for bone grafting, has several significant disadvantages including limited supply, donor site pain, hematoma formation, nerve and vascular injury, and fracture. Bone allografts have their own disadvantages including reduced osteoinductive capability, lack of osteoprogenitor cells, immunogenicity and risk of disease transmission. Thus demand exists for tissue-engineered constructs that can produce viable bone while avoiding the complications associated with human tissue grafts. This review will focus on recent advancements in tissue-engineered bone graft substitutes utilizing nanoscale technology in spine surgery applications. An evaluation will be performed of bone graft substitutes, biomimetic 3D scaffolds, bone morphogenetic protein, mesenchymal stem cells and intervertebral disc regeneration strategies. PMID- 26877155 TI - Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer. AB - Liver kinase B1 (LKB1) is a tumor suppressor, and its loss might lead to activation of the mammalian target of rapamycin (mTOR) and tumorigenesis. This study aimed to determine the clinical relevance of LKB1 gene and protein expression in breast cancer patients. LKB1 protein expression was evaluated using immunohistochemistry in tumors from early breast cancer patients in two Taiwanese medical centers. Data on LKB1 gene expression were obtained from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data set. The correlations between LKB1 expression, clinicopathologic factors, and patient outcome were analyzed. LKB1 expression was significantly associated with estrogen receptor (ER) expression in 2 of the 4 cohorts, but not with other clinicopathologic factors. LKB1 expression was not a predictor for relapse-free survival, overall survival (OS), or breast cancer-specific survival. In a subgroup analysis of the two Taiwanese cohorts, high LKB1 protein expression was predictive of high OS in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients (P = 0.013). Our study results indicate that LKB1 expression is not prognostic in the whole population of breast cancer patients, but it is a potential predictor of OS in the subset of HER2-positive patients. PMID- 26877157 TI - Serum sTREM-1 level is quite higher in Crimean Congo Hemorrhagic Fever, a viral infection. AB - Members of triggering receptor expressed on myeloid cells (TREM) family are known as immunmodulators in several infectious or noninfectious inflammatory disorders. The information about their role in viral infections is very limited. To enlighten if there is a relation between soluble TREM-1(sTREM-1) and a viral infection, Crimean Congo Haemorrhagic Fever (CCHF), we investigated the levels of sTREM-1 in the sera of 39 CCHF patients both at admission and at recovery and compared with 40 healthy controls by using microELISA technique. Statistical analysis was made by using Statistical Package for Social Sciences (SPSS) for Windows 20 programme. Value of P < 0.05 was accepted as significant for statistical analyses. Median sTREM-1 level was higher in CCHF group when compared to the control group (1,961 vs. 151.1 pg/ml, respectively; P < 0.001). In CCHF patients, sTREM-1 levels were significantly decreased at recovery compared to initial level measured at hospital admission (1,961 vs. 948 pg/ml, respectively; P = 0.019). DeltasTREM-1 is correlated with DeltaCRP, DeltaWBC, and DeltaPlt. We found that serum levels of sTREM-1 higher than 405.9 pg/ml existed as a cut off point for differentiating CCHF patients and control group with a sensitivity of 94.9% and specifity of 87.5%. It is proved that sTREM-1 is increased and correlates with the clinical and laboratory findings in CCHF, a viral infection characterized by activation of inflammation. This finding may lead new studies to enlighten the pathogenesis of infections developing by activation of inflammatory cascades and high level cytokine releases, especially. J. Med. Virol. 88:1473 1478, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26877158 TI - Optimizing the acceleration and resolution of three-dimensional fat image navigators for high-resolution motion correction at 7T. AB - PURPOSE: To investigate the effect of spatial resolution and parallel imaging acceleration factor on the quality of the motion estimates derived from image navigators with a three-dimensional (3D) gradient-recalled echo (GRE) acquisition with fat excitation (3D FatNavs) for neuroimaging at 7T. METHODS: Six healthy subjects were scanned for 10 min, during which time repeated GRE volumes were acquired during small movements-alternating between fat and water excitations (WaterNavs)-allowing retrospective decimation of the data to simulate a variety of combinations of image resolution and acceleration factor. Bias and error in the motion estimates were then compared across navigator parameters. RESULTS: The 2-mm, 4 * 4 accelerated data (TRvolume = 1.2 s) provided motion estimates that were almost indistinguishable from those from the full original acquisition (2 mm, 2 * 2, TRvolume = 5.2 s). For faster navigators, it was found that good accuracy and precision were achievable with TRvolume = 144 ms, using a lower spatial resolution (4 mm, 6 * 6 acceleration) to avoid the bias observed at exceptionally high acceleration factors (8 * 8 or higher). Parameter estimates from WaterNavs and FatNavs showed close agreement with FatNavs, with better performance at exceptionally high acceleration factors. CONCLUSION: Our data help to guide the parameter choice for 3D FatNavs when a compromise must be reached between the quality of the motion estimates and the available scan time. Magn Reson Med 77:547-558, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26877159 TI - Association between allergies and reduced risk of glioma. PMID- 26877160 TI - FDA confronts opioid addiction and overdose deaths. PMID- 26877161 TI - Oncologic Drugs Advisory Committee and conflicts of interest. PMID- 26877162 TI - Efficient mental workload estimation using task-independent EEG features. AB - OBJECTIVE: Mental workload is frequently estimated by EEG-based mental state monitoring systems. Usually, these systems use spectral markers and event-related potentials (ERPs). To our knowledge, no study has directly compared their performance for mental workload assessment, nor evaluated the stability in time of these markers and of the performance of the associated mental workload estimators. This study proposes a comparison of two processing chains, one based on the power in five frequency bands, and one based on ERPs, both including a spatial filtering step (respectively CSP and CCA), an FLDA classification and a 10-fold cross-validation. APPROACH: To get closer to a real life implementation, spectral markers were extracted from a short window (i.e. towards reactive systems) that did not include any motor activity and the analyzed ERPs were elicited by a task-independent probe that required a reflex-like answer (i.e. close to the ones required by dead man's vigilance devices). The data were acquired from 20 participants who performed a Sternberg memory task for 90 min (i.e. 2/6 digits to memorize) inside which a simple detection task was inserted. The results were compared both when the testing was performed at the beginning and end of the session. MAIN RESULTS: Both chains performed significantly better than random; however the one based on the spectral markers had a low performance (60%) and was not stable in time. Conversely, the ERP-based chain gave very high results (91%) and was stable in time. SIGNIFICANCE: This study demonstrates that an efficient and stable in time workload estimation can be achieved using task independent spatially filtered ERPs elicited in a minimally intrusive manner. PMID- 26877163 TI - Corrigendum: EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-beta oligomers and plaques. PMID- 26877164 TI - Influence of zinc on bacterial populations and their proteolytic enzyme activities in freshwater environments: a cross-site comparison. AB - Temporal responses of indigenous bacterial populations and proteolytic enzyme (i.e., aminopeptidase) activities in the bacterioplankton assemblages from 3 separate freshwater environments were examined after exposure to various zinc (Zn) concentrations under controlled microcosm conditions. Zn concentrations (ranging from 0 to 10 MUmol/L) were added to water samples collected from the Kalamazoo River, Rice Creek, and Huron River and examined for bacterial abundance and aminopeptidase activities at various time intervals over a 48 h incubation period in the dark. The results showed that the Zn concentrations did not significantly influence total bacterial counts directly; however, aminopeptidase activities varied significantly to increasing zinc treatments over time. Also, analysis of variance and linear regression analyses revealed significant positive relationships between bacterial numbers and their hydrolytic enzyme activities, suggesting that both probably co-vary with increasing Zn concentrations in aquatic systems. The results from this study serve as additional evidence of the ecological role of Zn as an extracellular peptidase cofactor on the dynamics of bacterial assemblages in aquatic environments. PMID- 26877165 TI - Evaluation of a temporary vaccination recommendation in response to an outbreak of invasive meningococcal serogroup C disease in men who have sex with men in Berlin, 2013-2014. AB - Meningococcal serogroup C (MenC) vaccination of men who have sex with men (MSM) was temporarily recommended to control an outbreak of invasive MenC disease among MSM in Berlin in 2012-2013. Vaccination was offered to HIV-infected MSM free of charge; others had to request reimbursement or pay out of pocket. We aimed to assess (i) awareness and acceptance of this recommendation through an online survey of MSM, (ii) implementation through a survey of primary care physicians and analysis of vaccine prescriptions, and (iii) impact through analysis of notified cases. Among online survey respondents, 60% were aware of the recommendation. Of these, 39% had obtained vaccination (70% of HIV-infected, 13% of HIV-negative/non-tested MSM). Awareness of recommendation and vaccination were positively associated with HIV infection, primary care physicians' awareness of respondents' sexual orientation, and exposure to multiple information sources. Most (26/30) physicians informed clients about the recommendation. Physicians considered concerns regarding reimbursement, vaccine safety and lack of perceived disease risk as primary barriers. After the recommendation, no further outbreak related cases occurred. To reach and motivate target groups, communication of a new outbreak-related vaccination recommendation should address potential concerns through as many information channels as possible and direct reimbursement of costs should be enabled. PMID- 26877168 TI - Tailoring treatments using treatment effect modification. AB - BACKGROUND AND OBJECTIVE: Applying results from clinical studies to individual patients can be a difficult process. Using the concept of treatment effect modification (also referred to as interaction), defined as a difference in treatment response between patient groups, we discuss whether and how treatment effects can be tailored to better meet patients' needs. RESULTS: First we argue that contrary to how most studies are designed, treatment effect modification should be expected. Second, given this expected heterogeneity, a small number of clinically relevant subgroups should be a priori selected, depending on the expected magnitude of effect modification, and prevalence of the patient type. Third, by defining generalizability as the absence of treatment effect modification we show that generalizability can be evaluated within the usual statistical framework of equivalence testing. Fourth, when equivalence cannot be confirmed, we address the need for further analyses and studies tailoring treatment towards groups of patients with similar response to treatment. Fifth, we argue that to properly frame, the entire body of evidence on effect modification should be quantified in a prior probability. PMID- 26877166 TI - Influence of light exposure at nighttime on sleep development and body growth of preterm infants. AB - Previous studies have demonstrated that a light-dark cycle has promoted better sleep development and weight gain in preterm infants than constant light or constant darkness. However, it was unknown whether brief light exposure at night for medical treatment and nursing care would compromise the benefits brought about by such a light-dark cycle. To examine such possibility, we developed a special red LED light with a wavelength of >675 nm which preterm infants cannot perceive. Preterm infants born at <36 weeks' gestational age were randomly assigned for periodic exposure to either white or red LED light at night in a light-dark cycle after transfer from the Neonatal Intensive Care Unit to the Growing Care Unit, used for supporting infants as they mature. Activity, nighttime crying and body weight were continuously monitored from enrolment until discharge. No significant difference in rest-activity patterns, nighttime crying, or weight gain was observed between control and experimental groups. The data indicate that nursing care conducted at 3 to 4-hour intervals exposing infants to light for <15 minutes does not prevent the infants from developing circadian rest activity patterns, or proper body growth as long as the infants are exposed to regular light-dark cycles. PMID- 26877169 TI - Self-administered methoxyflurane for procedural analgesia: experience in a tertiary Australasian centre. AB - Methoxyflurane, an agent formerly used as a volatile anaesthetic but that has strong analgesic properties, will soon become available again in the UK and Europe in the form of a small hand-held inhaler. We describe our experience in the use of inhaled methoxyflurane for procedural analgesia within a large tertiary hospital. In a small pilot crossover study of patients undergoing burns dressing procedures, self-administered methoxyflurane inhalation was preferred to ketamine-midazolam patient-controlled analgesia by five of eight patients. Patient and proceduralist outcomes and satisfaction were recorded from a subsequent case series of 173 minor surgical and radiological procedures in 123 patients performed using inhaled methoxyflurane. The procedures included change of dressing, minor debridement, colonoscopy and incision-and-drainage of abscess. There was a 97% success rate of methoxyflurane analgesia to facilitate these procedures. Limitations of methoxyflurane include maximal daily and weekly doses, and uncertainty regarding its safety in patients with pre-existing renal disease. PMID- 26877167 TI - Strain-dependent profile of misfolded prion protein aggregates. AB - Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration. PMID- 26877170 TI - In Memoriam: Lawrence Cohn. PMID- 26877171 TI - Very high or close to zero thermal expansion by the variation of the Sr/Ba ratio in Ba(1-x)Sr(x)Zn2Si2O7- solid solutions. AB - The compound BaZn2Si2O7 shows a highly positive coefficient of thermal expansion. At a temperature of 280 degrees C, it transforms to a high temperature phase, which exhibits a coefficient of thermal expansion near zero. The partial replacement of Ba(2+) against Sr(2+) leads to a decrease of the phase transition temperature. If more than 10% of Ba(2+) are replaced by Sr(2+), the high temperature phase is completely stable at room temperature and consequently, the thermal expansion is near zero or negative. The effect of the Sr(2+)/Ba(2+)-ratio on the phase transition temperature and the thermal expansion behavior is measured using high-temperature X-ray diffraction up to 1000 degrees C. The Sr(2+)/Ba(2+)-ratio strongly affects the overall thermal expansion as well as the anisotropy. The latter increases with decreasing Sr-concentration. The strong differences in the thermal expansion behavior between phases with the structure of the low-temperature phase and the high-temperature phase of BaZn2Si2O7 can be explained by a comparison of the ZnO4-chains inside these two crystal structures. PMID- 26877173 TI - Dual ultrasonic-assisted dispersive liquid-liquid microextraction coupled with microwave-assisted derivatization for simultaneous determination of 20(S) protopanaxadiol and 20(S)-protopanaxatriol by ultra high performance liquid chromatography-tandem mass spectrometry. AB - This paper, for the first time, reported a speedy hyphenated technique of low toxic dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual UADLLME) coupled with microwave-assisted derivatization (MAD) for the simultaneous determination of 20(S)-protopanaxadiol (PPD) and 20(S) protopanaxatriol (PPT). The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection using multiple-reaction monitoring (MRM) mode. A mass spectrometry sensitizing reagent, 4'-carboxy-substituted rosamine (CSR) with high reaction activity and ionization efficiency was synthesized and firstly used as derivatization reagent. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS conditions were all optimized in detail. Low toxic brominated solvents were used as extractant instead of traditional chlorinated solvents. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.010 and 0.015ng/mL for PPD and PPT, respectively) were achieved. The main advantages were rapid, sensitive and environmentally friendly, and exhibited high selectivity, accuracy and good matrix effect results. The proposed method was successfully applied to pharmacokinetics of PPD and PPT in rat plasma. PMID- 26877172 TI - Apocynin and ebselen reduce influenza A virus-induced lung inflammation in cigarette smoke-exposed mice. AB - Influenza A virus (IAV) infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Oxidative stress is increased in COPD, IAV-induced lung inflammation and AECOPD. Therefore, we investigated whether targeting oxidative stress with the Nox2 oxidase inhibitors and ROS scavengers, apocynin and ebselen could ameliorate lung inflammation in a mouse model of AECOPD. Male BALB/c mice were exposed to cigarette smoke (CS) generated from 9 cigarettes per day for 4 days. On day 5, mice were infected with 1 * 10(4.5) PFUs of the IAV Mem71 (H3N1). BALF inflammation, viral titers, superoxide production and whole lung cytokine, chemokine and protease mRNA expression were assessed 3 and 7 days post infection. IAV infection resulted in a greater increase in BALF inflammation in mice that had been exposed to CS compared to non smoking mice. This increase in BALF inflammation in CS-exposed mice caused by IAV infection was associated with elevated gene expression of pro-inflammatory cytokines, chemokines and proteases, compared to CS alone mice. Apocynin and ebselen significantly reduced the exacerbated BALF inflammation and pro inflammatory cytokine, chemokine and protease expression caused by IAV infection in CS mice. Targeting oxidative stress using apocynin and ebselen reduces IAV induced lung inflammation in CS-exposed mice and may be therapeutically exploited to alleviate AECOPD. PMID- 26877174 TI - Application of modified stir bar with nickel:zinc sulphide nanoparticles loaded on activated carbon as a sorbent for preconcentration of losartan and valsartan and their determination by high performance liquid chromatography. AB - In this study, the stir bar was coated for the first time with the nicel:zins sulphide nanoparticles (Ni:ZnS NPs) loaded on activated carbon (AC) (Ni:ZnS-AC) as well as 1-ethyl-3-methylimidazolium hexafluorophosphate ionic liquid (IL) using sol gel technique and was used for stir bar sorptive extraction (SBSE) of losartan (LOS) and valsartan (VAL) as the model compounds. The extracted analytes were then quantified by high performance liquid chromatography (HPLC) equipped with an ultra violet detector. The best extraction performance for LOS and VAL was obtained through the optimization of the parameters affecting SBSE including pH of sample solution, ionic strength, extraction time, volume of desorption solvent, desorption time, and stirring speed. The fractional factorial design (FFD) was used to find the most important parameters, which were then optimized by the central composite design (CCD) and the desirability function (DF). Under the optimal experimental conditions, wide linear ranges of 0.4-50MUgL(-1) and 0.5 50MUgL(-1) and good RSDs (at level of 5MUgL(-1) and n=6) of 4.4 and 4.9% were obtained for LOS and VAL, respectively. With the enrichment factors (EFs) of 188.6 and 184.8-fold, the limits of detection (LODs, S/N=3) of the developed method were found to be 0.12 and 0.15MUgL(-1) for LOS and VAL, respectively. The developed method was successfully applied to the determination of LOS and VAL in urine and plasma matrices. PMID- 26877175 TI - On-line coupling of immobilized cytochrome P450 microreactor and capillary electrophoresis: A promising tool for drug development. AB - In this work, the combination of an immobilized enzyme microreactor (IMER) based on the clinically important isoform cytochrome P450 2C9 (CYP2C9) with capillary electrophoresis (CE) is presented. The CYP2C9 was attached to magnetic SiMAG carboxyl microparticles using the carbodiimide method. The formation of an IMER in the inlet part of the separation capillary was ensured by two permanent magnets fixed in a cassette from the CE apparatus in the repulsive arrangement. The resulting on-line system provides an integration of enzyme reaction mixing and incubation, reaction products separation, detection and quantification into a single fully automated procedure with the possibility of repetitive use of the enzyme and minuscule amounts of reactant consumption. The on-line kinetic and inhibition studies of CYP2C9's reaction with diclofenac as a model substrate and sulfaphenazole as a model inhibitor were conducted in order to demonstrate its practical applicability. Values of the apparent Michalis-Menten constant, apparent maximum reaction velocity, Hill coefficient, apparent inhibition constant and half-maximal inhibition concentration were determined on the basis of the calculation of the effective substrate and inhibitor concentrations inside the capillary IMER using a model described by the Hagen-Poisseulle law and a novel enhanced model that reflects the influence of the reactants' diffusion during the injection process. PMID- 26877176 TI - Analysis of free hydroxytyrosol in human plasma following the administration of olive oil. AB - Hydroxytyrosol (HT) from olive oil, a potent bioactive molecule with health benefits, has a poor bioavailability, its free form (free HT) being undetectable so far. This fact leads to the controversy whether attained HT concentrations after olive oil polyphenol ingestion are too low to explain the observed biological activities. Due to this, an analytical methodology to determine free HT in plasma is crucial for understanding HT biological activity. Plasma HT instability and low concentrations have been major limitations for its quantification in clinical studies. Here, we describe a method to detect and quantify free HT in human plasma by using liquid chromatography coupled to tandem mass spectrometry. The method encompasses different steps of sample preparation including plasma stabilization, protein precipitation, selective derivatization with benzylamine, and purification by solid-phase extraction. A high sensitivity (LOD, 0.3ng/mL), specificity and stability of HT is achieved following these procedures. The method was validated and its applicability was demonstrated by analyzing human plasma samples after olive oil intake. A pharmacokinetic comparison was performed measuring free HT plasma concentrations following the intake of 25mL of ordinary olive oil (nearly undetectable concentrations) versus an extra-virgin olive oil (Cmax=4.40ng/mL). To our knowledge, this is the first time that an analytical procedure for quantifying free HT in plasma after olive oil dietary doses has been reported. The present methodology opens the door to a better understanding of the relationship between HT plasma concentrations and its beneficial health effects. PMID- 26877177 TI - Size exclusion chromatography of synthetic polymers and biopolymers on common reversed phase and hydrophilic interaction chromatography columns. AB - This work describes the applicability of common reversed phase and HILIC columns for size exclusion chromatography of synthetic and natural polymers. Depending on the nature of the solute and column stationary phase, a "non-retention" condition must be created with the aid of the mobile phase to achieve a unique size-based separation in isocratic mode. The various bonded phases show remarkable differences in size separations that are controlled by mobile phase conditions. Polymer-mobile phase and column-mobile phase solvation interactions determine polymer hydrodynamic volume (or solute bulkiness) and polymer-column steric interaction. Solvation interactions in turn depend on polymer, mobile phase and stationary phase polarities. Column-mobile phase solvation interactions determine the structural order of the bonded ligands that can vary from ordered (extended, aligned away from the silica substrate) to disordered (folded, pointing toward the silica substrate). Chain order increases with increased solvent penetration into the bonded phase. Increased chain order reduces pore volume, and therefore decreases the size-separation efficiency of a column. Conversely, decreased chain order increases pore volume and therefore increases the size-separation efficiency. The thermodynamic quality of the mobile phase also plays a significant role in the separation of polymers. "Poor" solvents can significantly reduce the hydrodynamic diameter of a solute and thus change their retention behavior. Medium polarity stationary phases, such as fluoro-phenyl and cyano, exhibit a unique retention behavior. With an appropriate polarity mobile phase, polar and non-polar synthetic polymers of the same molecular masses can be eluted at the same retention volumes. PMID- 26877178 TI - The application of capillary electrophoresis for assisting whole-cell aptamers selection by characterizing complete ssDNA distribution. AB - Whole-cell SELEX faces more difficulties than SELEX against purified molecules target. In this work, we demonstrate the application of capillary electrophoresis for assisting whole-cell aptamers selection by characterizing complete ssDNA distribution. We chose three cancer cell lines U251, Hela and PC3 as target, FAM labeled Sgc8c (a 41mer aptamer) and FAM labeled 41mer random ssDNA library as ssDNA model. CE conditions of running buffer and capillary length and inner diameter as well as UV and LIF detection were optimized. The distribution percentage of Sgc8c and ssDNA library against U251, Hela and PC3 was demonstrated, the relative peak area of their complex is 8.94%, 1.05% and 0.44% for Sgc8c and 9.03%, 1.04% and 0.12% for ssDNA library respectively. Under the chosen experimental conditions, binding ability comparison of three cell lines was U251>Hela>PC3, which was validated by laser confocol microscope. For each cell, distribution percentage of ssDNA library was compared with that of Sgc8c. Finally, whole-cell complex of U251-Sgc8c was confirmed by increase incubation time and fraction CE analysis. PMID- 26877179 TI - Determination of cellular glutathione:glutathione disulfide ratio in prostate cancer cells by high performance liquid chromatography with electrochemical detection. AB - A validated method has been developed for the simultaneous measurement of reduced and oxidized glutathione in de-proteinised cellular extracts. This has been used to compare models of malignant and non-malignant human prostate cell lines. Analysis of LNCaP and DU145 cells showed a glutathione to glutathione disulfide ratio of 8:1 and 32:1 respectively, whilst the control cell line, PZ-HPV7 displayed a ratio of 93:1. Results indicate that the more aggressive phenotype displays adaptation to increased oxidative stress via up regulation of glutathione turnover. It was also noted that in the LNCaP and DU145 cell line, glutathione was only responsible for ca. 60% and 79% respectively, of the total cellular reduced thiol; indicating the presence of other biological thiols. PMID- 26877180 TI - Mixed hemimicelles solid-phase extraction based on sodium dodecyl sulfate-coated nano-magnets for selective adsorption and enrichment of illegal cationic dyes in food matrices prior to high-performance liquid chromatography-diode array detection detection. AB - In this study, mixed hemimicelles solid-phase extraction (MHSPE) based on sodium dodecyl sulfate (SDS) coated nano-magnets Fe3O4 was investigated as a novel method for the extraction and separation of four banned cationic dyes, Auramine O, Rhodamine B, Basic orange 21 and Basic orange 22, in condiments prior to HPLC detection. The main factors affecting the extraction of analysts, such as pH, surfactant and adsorbent concentrations and zeta potential were studied and optimized. Under optimized conditions, the proposed method was successful applied for the analysis of banned cationic dyes in food samples such as chili sauce, soybean paste and tomato sauce. Validation data showed the good recoveries in the range of 70.1-104.5%, with relative standard deviations less than 15%. The method limits of determination/quantification were in the range of 0.2-0.9 and 0.7 3MUgkg(-1), respectively. The selective adsorption and enrichment of cationic dyes were achieved by the synergistic effects of hydrophobic interactions and electrostatic attraction between mixed hemimicelles and the cationic dyes, which also resulted in the removal of natural pigments interferences from sample extracts. When applied to real samples, RB was detected in several positive samples (chili powders) within the range from 0.042 to 0.177mgkg(-1). These results indicate that magnetic MHSPE is an efficient and selective sample preparation technique for the extraction of banned cationic dyes in a complex matrix. PMID- 26877181 TI - Optimization of large-scale pseudotargeted metabolomics method based on liquid chromatography-mass spectrometry. AB - Liquid chromatography-mass spectrometry (LC-MS) is now a main stream technique for large-scale metabolic phenotyping to obtain a better understanding of genomic functions. However, repeatability is still an essential issue for the LC-MS based methods, and convincing strategies for long time analysis are urgently required. Our former reported pseudotargeted method which combines nontargeted and targeted analyses, is proved to be a practical approach with high-quality and information rich data. In this study, we developed a comprehensive strategy based on the pseudotargeted analysis by integrating blank-wash, pooled quality control (QC) sample, and post-calibration for the large-scale metabolomics study. The performance of strategy was optimized from both pre- and post-acquisition sections including the selection of QC samples, insertion frequency of QC samples, and post-calibration methods. These results imply that the pseudotargeted method is rather stable and suitable for large-scale study of metabolic profiling. As a proof of concept, the proposed strategy was applied to the combination of 3 independent batches within a time span of 5 weeks, and generated about 54% of the features with coefficient of variations (CV) below 15%. Moreover, the stability and maximal capability of a single analytical batch could be extended to at least 282 injections (about 110h) while still providing excellent stability, the CV of 63% metabolic features was less than 15%. Taken together, the improved repeatability of our strategy provides a reliable protocol for large-scale metabolomics studies. PMID- 26877182 TI - Women with Turner syndrome are at high risk of lifestyle-related disease -From questionnaire surveys by the Foundation for Growth Science in Japan. AB - In this study, the prevalence of obesity and complications of lifestyle-related diseases, such as diabetes mellitus, hypertension, dyslipidemia and liver dysfunction, as well as the relationship with karyotypes, were investigated in 492 patients with Turner syndrome (TS) aged 17 years or older. Data were obtained through questionnaire surveys administered by attending physicians throughout Japan. Collected data were compared with data from the National Health and Nutrition Survey. Patient ages ranged from 17.1 to 42.5 years (mean +/- standard error, 26.6+/-0.2). The prevalence of lifestyle-related diseases at age 20 or over was 6.3% for diabetes, 8.7% for hypertension, 20.2% for dyslipidemia and 12.4% for liver dysfunction. These four diseases were clearly associated with severity of obesity. Obesity (BMI >=25 kg/m(2)) was observed in 106 out of 426 patients with TS aged 15 to 39 years (24.7%) and the prevalence was significantly higher than that of the general female population (9.4%). The mean BMI in age subgroups without any complications ranged from 21.2 to 22.7, which although was within normal ranges was significantly higher than that in the general female population (20.3-21.3). In this study population, patients with TS had more complications related to lifestyle-related diseases that were highly related to obesity. Few associations between complications and karyotypes were found. In the follow-up of patients with TS, the presence of lifestyle-related disease should be considered in the evaluation and treatment of the disease. PMID- 26877183 TI - Correction: Graphene-catalyzed photoreduction of dye molecules revealed by graphene enhanced Raman spectroscopy. AB - Correction for 'Graphene-catalyzed photoreduction of dye molecules revealed by graphene enhanced Raman spectroscopy' by Bora Lee et al., Phys. Chem. Chem. Phys., 2016, 18, 3413-3415. PMID- 26877184 TI - Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps). AB - A toxicovenomic study was performed on the venom of the green mamba, Dendroaspis angusticeps. Forty-two different proteins were identified in the venom of D. angusticeps, in addition to the nucleoside adenosine. The most abundant proteins belong to the three-finger toxin (3FTx) (69.2%) and the Kunitz-type proteinase inhibitor (16.3%) families. Several sub-subfamilies of the 3FTxs were identified, such as Orphan Group XI (Toxin F-VIII), acetylcholinesterase inhibitors (fasciculins), and aminergic toxins (muscarinic toxins, synergistic-like toxins, and adrenergic toxins). Remarkably, no alpha-neurotoxins were identified. Proteins of the Kunitz-type proteinase inhibitor family include dendrotoxins. Toxicological screening revealed a lack of lethal activity in all RP-HPLC fractions, except one, at the doses tested. Thus, the overall toxicity depends on the synergistic action of various types of proteins, such as dendrotoxins, fasciculins, and probably other synergistically-acting toxins. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality. These antivenoms also showed a pattern of broad immunorecognition of the different HPLC fractions by ELISA and immunoprecipitated the crude venom by gel immunodiffusion. The synergistic mechanism of toxicity constitutes a challenge for the development of effective recombinant antibodies, as it requires the identification of the most relevant synergistic toxins. BIOLOGICAL SIGNIFICANCE: Envenomings by elapid snakes of the genus Dendroaspis, collectively known as mambas, represent a serious medical problem in sub-Saharan Africa. The development of novel antivenoms and of recombinant neutralizing antibodies demands the identification of the most relevant toxins in these venoms. In this study, a bottom-up approach was followed for the study of the proteome of the venom of the Eastern green mamba, D. angusticeps. Forty-two different proteins were identified, among which the three finger toxin (3FTx) family, characteristic of elapid venoms, was the most abundant, followed by the Kunitz-type proteinase inhibitor family. In addition, several other protein families were present in the venom, together with the nucleoside adenosine. No alpha-neurotoxins were identified within the family of 3FTxs in the venom of D. angusticeps, in contrast to the venom of Dendroaspis polylepis, in which alpha-neurotoxins are largely responsible for the toxicity. With one exception, HPLC fractions from D. angusticeps venom did not kill mice at the doses tested. This underscores that the toxicity of the whole venom is due to the synergistic action of various components, such as fasciculins and dendrotoxins, and probably other synergistically-acting toxins. Thus, the venoms of these closely related species (D. angusticeps and D. polylepis) seem to have different mechanisms to subdue their prey, which may be related to different prey preferences, as D. angusticeps is predominantly arboreal, whereas D. polylepis lives mostly in open bush country and feeds mainly on mammals. It is therefore likely that the predominant clinical manifestations of human envenomings by these species also differ, although in both cases neurotoxic manifestations predominate. Polyspecific antivenoms manufactured in South Africa and India were effective in the neutralization of venom-induced lethality in mice and showed a pattern of broad immunorecognition of the various venom fractions. It is necessary to identify the toxins responsible for the synergistic mode of toxicity in this venom, since they are the targets for the development of recombinant antibodies for the treatment of envenomings. PMID- 26877185 TI - Changes over lactation in breast milk serum proteins involved in the maturation of immune and digestive system of the infant. AB - To objective of this study was to better understand the biological functions of breast milk proteins in relation to the growth and development of infants over the first six months of life. Breast milk samples from four individual women collected at seven time points in the first six months after delivery were analyzed by filter aided sample preparation and dimethyl labeling combined with liquid chromatography tandem mass spectrometry. A total of 247 and 200 milk serum proteins were identified and quantified, respectively. The milk serum proteome showed a high similarity (80% overlap) on the qualitative level between women and over lactation. The quantitative changes in milk serum proteins were mainly caused by three groups of proteins, enzymes, and transport and immunity proteins. Of these 21 significantly changed proteins, 30% were transport proteins, such as serum albumin and fatty acid binding protein, which are both involved in transporting nutrients to the infant. The decrease of the enzyme bile salt activated lipase as well as the immunity proteins immunoglobulins and lactoferrin coincide with the gradual maturation of the digestive and immune system of infants. The human milk serum proteome didn't differ qualitatively but it did quantitatively, both between mothers and as lactation advanced. The changes of the breast milk serum proteome over lactation corresponded with the development of the digestive and immune system of infants. BIOLOGICAL SIGNIFICANCE: Breast milk proteins provide nutrition, but also contribute to healthy development of infants. Despite the previously reported large number of identified breast milk proteins and their changes over lactation, less is known on the changes of these proteins in individual mothers. This study is the first to determine the qualitative and quantitative changes of milk proteome over lactation between individual mothers. The results indicate that the differences in the milk proteome between individual mothers are more related to the quantitative level than qualitative level. The correlation between the changes of milk proteins and the gradual maturation of the gastrointestinal tract and immune system in infants, contributes to a better understanding of the biological functions of human milk proteins for the growth and development of infants. PMID- 26877186 TI - EC4U: results from a pilot project integrating the copper IUC into emergency contraceptive care. AB - OBJECTIVE: The copper intrauterine contraceptive (IUC) is the most effective method of emergency contraception (EC), yet it is underutilized. The objective was to evaluate a pilot project integrating the copper IUC into EC care. STUDY DESIGN: Single-group evaluation study. Nine geographically diverse reproductive health centers implemented 6-month pilot interventions. All interventions included staff education and inclusion of the IUC in EC patient counseling; some sites developed patient education materials. Health center staff completed manual monthly tracking forms of the number of EC patients receiving oral levonorgestrel, ulipristal acetate or the copper IUC. Sites also tracked and reported the number of patients returning for removal during the 6-month pilot period and for 5 subsequent months. Main study outcomes included the number of IUC for EC insertions, the proportion that were same-day insertions and the proportion of patients receiving each EC type during the pilot period. A secondary outcome was the number of patients who had returned for removal at 5 months postpilot. RESULTS: There were 101 IUC insertions for EC during the pilot period. Seventy-seven percent were same-day insertions; the remainder returned for insertion within 5 days of unprotected intercourse. The percentage of EC patients choosing the IUC varied by site from 1 to 16% (overall=7%). At 5 months postpilot, 20 patients (20%) had returned for removal. CONCLUSIONS: Some women will be interested in the copper IUC for EC, and therefore, all women should be offered this option. Results suggest that the large majority continued to use the IUC for ongoing contraception. IMPLICATIONS: Copper IUCs are a viable option for women in need of EC. All women should be offered the most effective EC option. PMID- 26877187 TI - Tissue factor as a link between inflammation and coagulation. AB - Due to its receptor activity for factor VII, tissue factor (TF) is primary initiator of the blood coagulation cascade and ensures rapid hemostasis in case of organ damage. Inflammatory cytokines, such as tumor necrosis factor-alpha or interleukins, strongly induce expression of both full-length TF as well as the alternatively spliced TF in endothelial and blood cells. Beyond its role in hemostasis, TF also has signaling activity and promotes pleiotropic inflammatory responses via protease-activated receptors in concert with other coagulation factors. Alteration of TF expression and TF alternative splicing provides an effective means to change the endothelial phenotype and modulate inflammatory responses of the vessel. PMID- 26877189 TI - What language is the language-ready brain ready for?: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26877188 TI - Lipids implicated in the journey of a secretory granule: from biogenesis to fusion. AB - The regulated secretory pathway begins with the formation of secretory granules by budding from the Golgi apparatus and ends by their fusion with the plasma membrane leading to the release of their content into the extracellular space, generally following a rise in cytosolic calcium. Generation of these membrane bound transport carriers can be classified into three steps: (i) cargo sorting that segregates the cargo from resident proteins of the Golgi apparatus, (ii) membrane budding that encloses the cargo and depends on the creation of appropriate membrane curvature, and (iii) membrane fission events allowing the nascent carrier to separate from the donor membrane. These secretory vesicles then mature as they are actively transported along microtubules toward the cortical actin network at the cell periphery. The final stage known as regulated exocytosis involves the docking and the priming of the mature granules, necessary for merging of vesicular and plasma membranes, and the subsequent partial or total release of the secretory vesicle content. Here, we review the latest evidence detailing the functional roles played by lipids during secretory granule biogenesis, recruitment, and exocytosis steps. In this review, we highlight evidence supporting the notion that lipids play important functions in secretory vesicle biogenesis, maturation, recruitment, and membrane fusion steps. These effects include regulating various protein distribution and activity, but also directly modulating membrane topology. The challenges ahead to understand the pleiotropic functions of lipids in a secretory granule's journey are also discussed. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). PMID- 26877190 TI - Thyroid dysfunction and hepatic steatosis in overweight children and adolescents. AB - BACKGROUND: Overt or subclinical hypothyroidism is a common finding in adult populations affected by non-alcoholic fatty liver disease (NAFLD). Currently, there are only sparse data available on the association of thyroid dysfunction and NAFLD in obese children and adolescents. OBJECTIVE: The study aims to investigate the association of thyroid function test values with NAFLD and metabolic risk factors in a population of obese children and adolescents. METHODS: A total of 332 overweight and obese children and adolescents (170 girls) aged between 10 and 19 years were analysed. Subjects underwent ultrasound examination of the liver. Thyroid function was evaluated by laboratory determination of thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine levels. All included subjects were either euthyroid or had subclinical hypothyroidism (TSH > 4 MUU mL-1 , normal thyroxine). Further metabolic profiling included the determination of lipid status, insulin and liver function tests. Anthropometric parameters body mass index, waist and hip circumference were documented. RESULTS: The prevalence of hepatic steatosis was 29.8%. Subjects with NAFLD had significantly higher TSH levels than those without (p = 0.0007). After dividing TSH values into quartiles, both univariate and multivariate analyses (adjusted for age, body mass index-standard deviation scores and stage of puberty) showed a significant association with hepatic steatosis (p < 0.05). CONCLUSION: Taking possible variables into consideration, our results show that there is a significant association between hepatic steatosis and the TSH levels in obese children and adolescents. Mild thyroid dysfunction may therefore have a role in determining an unfavourable metabolic profile in obese children and adolescents. PMID- 26877191 TI - Clinically Significant Drug Interaction Between Clotrimazole and Tacrolimus in Pancreas Transplant Recipients and Associated Risk of Allograft Rejection. AB - STUDY OBJECTIVE: To examine the clinical significance of clotrimazole troche discontinuation on tacrolimus trough levels and risk of allograft rejection after pancreas transplantation. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Sixty-five pancreas transplant recipients (simultaneous pancreas-kidney transplants [39 patients], pancreas after kidney transplants [4 patients], and pancreas transplant alone [22 patients]) who were discharged after transplantation receiving a maintenance immunosuppressive regimen of tacrolimus, mycophenolate, and prednisone, and a clotrimazole troche to prevent oral mucosal candidiasis; per protocol, the clotrimazole troche was discontinued at 3 months after transplantation. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 1 year after transplantation. The primary outcome measure was the difference in tacrolimus trough level before and after discontinuation of the clotrimazole troche. The secondary outcome measure was the difference in tacrolimus trough level when patients were stratified by the cohort that had a documented rejection episode 3-12 months after transplantation (rejection group) and the cohort that did not experience a rejection episode (no-rejection group). The incidence of rejection was evaluated in relation to mean tacrolimus trough concentrations above or below a protocol-defined level of significance (6 ng/ml). For the primary outcome, the mean tacrolimus trough level before discontinuation of the clotrimazole troche was significantly higher than the mean trough level after discontinuation (mean +/- SD 9.6 +/- 3.0 ng/ml vs 7.1 +/- 2.6 ng/ml, p = 0.000003). For the secondary outcome, the mean tacrolimus trough level difference before and after clotrimazole troche discontinuation remained significant in both the no-rejection group (9.5 +/- 3.0 ng/ml vs 7.4 +/- 2.4 ng/ml, p = 0.00007) and rejection group (10.9 +/- 3.3 ng/ml vs 4.1 +/- 2.5 ng/ml, p = 0.0008). Between groups, the mean tacrolimus serum trough level after clotrimazole troche discontinuation was lower in the rejection group (4.1 +/- 2.5 ng/ml) than that in the no-rejection group (7.4 +/- 2.4 ng/ml; p = 0.005). The mean tacrolimus trough level difference between before and after discontinuation was greater in the rejection group (6.8 +/- 1.5 ng/ml) versus the no-rejection group (2.1 +/- 3.8 ng/ml, p = 0.009). Tacrolimus trough levels below 6 ng/ml (19 patients) after clotrimazole troche discontinuation were associated with an increased incidence of rejection episodes within 3-12 months after transplantation (odds ratio 12, 95% confidence interval 1.24-115.91, p = 0.032) versus trough levels of 6 ng/ml or higher (46 patients). CONCLUSION: Clotrimazole troche discontinuation at 3 months after transplantation may cause significant tacrolimus trough level reductions. In addition, when trough levels are below 6 ng/ml, these fluctuations may contribute to the occurrence of allograft rejection. PMID- 26877195 TI - Chronic fatigue syndrome and sleep disorders: clinical associations and diagnostic difficulties. AB - INTRODUCTION: Chronic fatigue syndrome (CFS) is characterised by the presence of intractable fatigue and non-restorative sleep, symptoms which are also very prevalent in multiple diseases and appear as side effects of different drugs. Numerous studies have shown a high prevalence of sleep disorders in patients with CFS. However, non-restorative sleep and fatigue are frequently symptoms of the sleep disorders themselves, so primary sleep disorders have to be ruled out in many cases of CFS. DEVELOPMENT: This review was performed using a structured search of the MeSH terms ([Sleep]+[Chronic fatigue syndrome]) in the PubMed database. CONCLUSION: Identifying primary sleep disorders in patients meeting diagnostic criteria for CFS will allow for a more comprehensive treatment approach involving new diagnostic and therapeutic strategies that may improve quality of life for these patients. PMID- 26877192 TI - Principles and procedures for implementation of ICH M7 recommended (Q)SAR analyses. AB - The ICH M7 guideline describes a consistent approach to identify, categorize, and control DNA reactive, mutagenic, impurities in pharmaceutical products to limit the potential carcinogenic risk related to such impurities. This paper outlines a series of principles and procedures to consider when generating (Q)SAR assessments aligned with the ICH M7 guideline to be included in a regulatory submission. In the absence of adequate experimental data, the results from two complementary (Q)SAR methodologies may be combined to support an initial hazard classification. This may be followed by an assessment of additional information that serves as the basis for an expert review to support or refute the predictions. This paper elucidates scenarios where additional expert knowledge may be beneficial, what such an expert review may contain, and how the results and accompanying considerations may be documented. Furthermore, the use of these principles and procedures to yield a consistent and robust (Q)SAR-based argument to support impurity qualification for regulatory purposes is described in this manuscript. PMID- 26877193 TI - FLEXITau: Quantifying Post-translational Modifications of Tau Protein in Vitro and in Human Disease. AB - Tauopathies, including Alzheimer's disease (AD), are associated with the aggregation of modified microtubule associated protein tau. This pathological state of tau is often referred to as "hyperphosphorylated". Due to limitations in technology, an accurate quantitative description of this state is lacking. Here, a mass spectrometry-based assay, FLEXITau, is presented to measure phosphorylation stoichiometry and provide an unbiased quantitative view of the tau post-translational modification (PTM) landscape. The power of this assay is demonstrated by measuring the state of hyperphosphorylation from tau in a cellular model for AD pathology, mapping, and calculating site occupancies for over 20 phosphorylations. We further employ FLEXITau to define the tau PTM landscape present in AD post-mortem brain. As shown in this study, the application of this assay provides mechanistic understanding of tau pathology that could lead to novel therapeutics, and we envision its further use in prognostic and diagnostic approaches for tauopathies. PMID- 26877194 TI - Reproductive intentions and family planning practices of pregnant HIV-infected Malawian women on antiretroviral therapy. AB - The objective of this study was to describe the pregnancy intentions of pregnant HIV-infected Malawian women on antiretroviral therapy (ART) for at least 6 months prior to the current pregnancy, and to assess whether time on ART was associated with pregnancy intention. We conducted a cross-sectional analysis of HIV-infected Malawian women receiving antenatal care at a government hospital with a survey assessing ART history, reproductive history, and family planning use at conception. We used Pearson's chi-square tests and Fisher's exact tests to compare these parameters between women on ART greater than 24 months with those on ART less than 24 months. Modified Poisson regression was performed to assess the association between time on ART and pregnancy intention. Most women (75%) reported that their current pregnancy was unintended, defined as either Mistimed (21%) or Unwanted (79%). Women on ART for longer than 2 years were more likely to report an unintended pregnancy (79% versus 65%, p = .03), though there was no significant association between time on ART and pregnancy intention in multivariate analysis. Most women (79%) were using contraception at the time of conception, with condoms being most popular (91%), followed by injectables (9%) and the implant (9%). HIV-infected women on ART continue to experience high rates of unintended pregnancy in the Option B+ era. As Option B+ continues to be implemented in Malawi and increasing numbers of HIV-infected women initiate lifelong ART, ensuring that the most effective forms of contraception are accessible is necessary to decrease unintended pregnancy. PMID- 26877196 TI - Adaptation and validation of a Spanish-language version of the Frontotemporal Dementia Rating Scale (FTD-FRS). AB - INTRODUCTION: The Frontotemporal Dementia Rating Scale (FTD-FRS) is a tool designed to aid with clinical staging and assessment of the progression of frontotemporal dementia (FTD-FRS). OBJECTIVE: Present a multicentre adaptation and validation study of a Spanish version of the FRS. METHODOLOGY: The adapted version was created using 2 translation-back translation processes (English to Spanish, Spanish to English) and verified by the scale's original authors. We validated the adapted version in a sample of consecutive patients diagnosed with FTD. The procedure included evaluating internal consistency, testing unidimensionality with the Rasch model, analysing construct validity and discriminant validity, and calculating the degree of agreement between the Clinical Dementia Rating scale (CDR) and FTD-FRS for FTD cases. RESULTS: The study included 60 patients with DFT. The mean score on the FRS was 12.1 points (SD=6.5; range, 2-25) with inter-group differences (F=120.3; df=3; P<.001). Cronbach's alpha was 0.897 and principal component analysis of residuals delivered an acceptable eigenvalue for 5 contrasts (1.6-2.7) and 36.1% raw variance. FRS was correlated with the Mini-mental State Examination (r=0.572; P<.001) and functional capacity (DAD; r=0.790; P<.001). FTD-FRS also showed a significant correlation with CDR (r=-0.641; P<.001), but we did observe variability in the severity levels; cases appeared to be less severe according to the CDR than when measured with the FTD-FRS (kappa=0.055). CONCLUSIONS: This process of validating the Spanish translation of the FTD-FRS yielded satisfactory results for validity and unidimensionality (severity) in the assessment of patients with FTD. PMID- 26877197 TI - Fusarium ramigenum, a novel human opportunist in a patient with common variable immunodeficiency and cellular immune defects: case report. AB - BACKGROUND: Fusarium species are ubiquitous environmental fungi that occasionally provoke serious invasive infections in immunocompromised hosts. Among Fusarium species, Fusarium ramigenum, belonging to the Fusarium fujikuroi species complex, has thus far never been found to cause human infections. Here we describe the first case of invasive fusariosis caused by Fusarium ramigenum in a human and also identify immunological deficiencies that most likely contributed to invasiveness. CASE PRESENTATION: A 32-year-old Caucasian male with a seemingly insignificant medical history of mild respiratory illness during the preceding two years, developed invasive pulmonary fusariosis. Detailed immunological assessment revealed the presence of common variable immunodeficiency, complicated by a severe impairment of the capacity of T-cells to produce both gamma interferon and interleukin-17. In-depth microbiological assessment identified the novel human opportunistic pathogen Fusarium ramigenum as cause of the infection. CONCLUSION: This report demonstrated that an opportunistic invasive fungal infection may indicate an underlying cellular immune impairment of the host. The unexpected invasive infection with Fusarium ramigenum in this case unmasked a complex combined humoral and cellular immunological deficiency. PMID- 26877198 TI - Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn). AB - Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer. PMID- 26877199 TI - Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus. AB - Early life stress (ELS) exerts long-lasting epigenetic influences on the brain and makes an individual susceptible to later depression. It is poorly understood whether ELS and subsequent adult chronic stress modulate epigenetic mechanisms. We examined the epigenetic mechanisms of the BDNF gene in the hippocampus, which may underlie stress vulnerability to postnatal maternal separation (MS) and adult restraint stress (RS). Rat pups were separated from their dams (3 h/day from P1 P21). When the pups reached adulthood (8 weeks old), we introduced RS (2 h/day for 3 weeks) followed by escitalopram treatment. We showed that both the MS and RS groups expressed reduced levels of total and exon IV BDNF mRNA. Furthermore, RS potentiated MS-induced decreases in these expression levels. Similarly, both the MS and RS groups showed decreased levels of acetylated histone H3 and H4 at BDNF promoter IV, and RS exacerbated MS-induced decreases of H3 and H4 acetylation. Both the MS and RS groups had increased MeCP2 levels at BDNF promoter IV, as well as increased HDAC5 mRNA, and the combination of MS and RS exerted a greater effect on these parameters than did RS alone. In the forced swimming test, the immobility time of the MS + RS group was significantly higher than that of the RS group. Additionally, chronic escitalopram treatment recovered these alterations. Our results suggest that postnatal MS and subsequent adult RS modulate epigenetic changes in the BDNF gene, and that these changes may be related to behavioral phenotype. These epigenetic mechanisms are involved in escitalopram action. PMID- 26877200 TI - Vitamin D supplementation during pregnancy: Updated meta-analysis on maternal outcomes. AB - BACKGROUND: Vitamin D deficiency is highly prevalent during pregnancy. It has been suggested that vitamin D supplementation during pregnancy may reduce the risk of adverse gestational outcomes. OBJECTIVES: To update a previous meta analysis on the effects of oral vitamin D supplementation (alone or in combination with other vitamins and minerals) during pregnancy on maternal 25(OH)D levels and risk of developing pre-eclampsia, gestational diabetes, preterm birth, impaired glucose tolerance, caesarean section, gestational hypertension and other adverse conditions. METHODS: We searched for randomized and quasi-randomized trials through the Cochrane Pregnancy and Childbirth Group's Trials Register, the International Clinical Trials Registry Platform, the Networked Digital Library of Theses and Dissertations, and direct communications with relevant organizations. Assessments of inclusion criteria, extraction of data from included studies, and risk of bias' assessments of the included studies were done independently by two review authors. RESULTS: We included 15 trials, excluded 27 trials and 23 trials are still ongoing/unpublished. Data from seven trials with 868 women suggest that pregnant women supplemented with vitamin D had significantly higher 25(OH)D levels compared to controls (mean difference: 54.7nmol/L; 95% CI 36.6, 72.9). Two trials found a lower risk of preeclampsia (8.9% versus 15.5%; average risk ratio 0.52; 95% CI 0.25, 1.05) and two other trials found no difference in the risk of gestational diabetes with vitamin D supplementation. Also, three trials found that supplementation with vitamin D plus calcium reduced the risk of pre-eclampsia (5% versus 9%; average risk ratio 0.51; 95% CI 0.32, 0.80). CONCLUSION: Supplementing pregnant women with vitamin D led to significantly higher levels of 25(OH)D at term compared to placebo/control but results were inconsistent. Vitamin D supplementation, with or without calcium, may be related to lower risk of preeclampsia but more studies are needed to confirm this. PMID- 26877201 TI - Effect of a transcriptional inactive or absent vitamin D receptor on beta-cell function and glucose homeostasis in mice. AB - Vitamin D deficiency is associated with beta-cell dysfunction and a higher risk of diabetes, but mice and humans with an absence of the vitamin D receptor (VDR) display normal glucose tolerance. Here, we investigated the direct effects of absence of VDR or absence of ligand activation of VDR on beta-cell function. For this purpose, we generated mice, with a mutation in the AF2 domain of Vdr (VDRDeltaAF2), preventing ligand-driven transcriptional activation of vitamin D responsive genes. VDRDeltaAF2 mice were compared to Vdr full knockout (VDR-/-) and wild type (WT) mice. In order to avoid hypocalcemia, which has a direct effect on beta-cell function, mice were fed a high calcium, high lactose diet yielding comparable serum calcium in all mice. While VDR-/- mice developed extensive alopecia by the age of 24 weeks, the fur of VDRDeltaAF2 remained normal. All VDRDeltaAF2 mice weighed significantly less than WT, while male but not female VDR-/- mice had a lower body weight than WT mice. Dual-energy X-ray absorptiometry showed that both VDRDeltaAF2 (17.2% (females) and 16.6% (males)) and VDR-/- (15.7% and 14.8%) mice have a lower percentage of body fat (vs 19.3% and 22.2% in WT). Serum 25(OH)D3 concentrations were lower for both VDRDeltaAF2 ( 4.55 fold, P<0.001) and VDR-/- (-3.7 fold, P<0.001) as compared to 12 week old WT mice, while serum 1,25(OH)2D3 was increased for both strains 94.5 fold (P<0.01) and 92.8 fold (P<0.001) for VDRDeltaAF2 and VDR-/- vs WT, respectively). In vivo glucose tolerance tests performed at 12 and 24 weeks of age, as well as ex vivo glucose stimulated insulin secretion on freshly isolated islets, revealed no major differences between the three strains. Microarray analysis on freshly isolated islets showed only 1 differentially expressed gene, phosphodiesterase 10a (Pde10a), which was 2.16 and 1.75 fold up-regulated in VDRDeltaAF2 and VDR-/- islets as compared to WT islets, respectively (P<=0.001). We conclude that in the presence of normocalcemia, absence of VDR or its ligand-activated transcription of genes has no direct regulatory effect on murine glucose homeostasis or gene expression in islets of Langerhans. PMID- 26877202 TI - Prevalence and treatment of hypovitaminosis D in the haemodialysis population of Coventry. AB - Low serum 25(OH)D and associated bone and non-bone related problems are not well appreciated in end stage renal disease (ESRD). Vitamin D treatment strategies in the UK currently focus almost exclusively on calcitriol [1,25(OH)2D], alfacalcidol or paricalcitol. In ESRD hypovitaminosis D is associated with bone loss, muscle weakness, falls, fractures and increased inflammation. National guidelines changed in 2014 and now recommend the diagnosis and treatment of low serum 25(OH)D in all patients with glomerular filtration rate (GFR) less than 30ml/min/1.73m2. However as yet there are no standardized guidelines for dosage, frequency and monitoring in ESRD patients. Following a systematic review of the literature we developed a clinical guideline for cholecalciferol supplementation at University Hospitals of Coventry and Warwickshire, UK. The guideline recommends 40,000IU cholecalciferol weekly for patients with 25(OH)D <50nmol/L and 20,000IU weekly for patients with 25(OH)D 50-75nmol/L; to be continued long term unless levels increase to >=150nmol/L. To date we have measured 25(OH)D levels in 385 in-center haemodialysis patients. Virtually all patients (95%) had serum 25(OH)D levels <75nmol/L (65% deficient, <30nmol/L; 30% insufficient, 30 74nmol/L). Only 5% of patients had optimal levels (>=75nmol/L). Our data indicates that hypovitaminosis D is prevalent in the haemodialysis population in Coventry and Warwickshire and this is likely to reflect UK haemodialysis patients, highlighting the need for a national supplementation guideline. PMID- 26877203 TI - Vitamin D deficiency: A single centre analysis of patients from 136 countries. AB - Vitamin D deficiency is a global problem, thought to be related to lack of sunlight exposure, and usually accompanied by reduced dietary intake. This study was designed to determine vitamin D status of 60,979 patients admitted to the Burjeel Hospital of VPS healthcare in Abu Dhabi, United Arab Emirates (UAE) from October 2012 to September 2014. The total concentrations of vitamin D [25(OH)D] of all the studied patients were measured in a single laboratory. Of the studied patients, 57.5% were female and 42.5% were male. Serum 25(OH)D (total) measurements showed 82.5% of the studied patients have vitamin D deficiency to insufficiency. 26.4% of females and 18.4% of males have extreme deficiency of 25(OH)D. There was higher variability of vitamin D in group of females then males according to coefficient of variation. In our studied cohort teenagers (13-19 years) have shown the lowest levels of serum vitamin D (data not shown and will be communicated as a separate publication). The prevalence of hypovitaminosis D is significantly high among population of UAE, Saudi Arabia and many Middle Eastern countries, especially among women, despite abundant sunshine. 86.1% UAE nationals and 78.9% visitors of other nationalities were found <75nmol/L of 25(OH)D. 28.4% of UAE nationals and 17.5% of visitors of other nationalities have extreme deficiency of 25(OH)D. Our results are significant, as all of our patients are residing permanently in the UAE or visitors that has yearlong sunlight. In addition, measuring 25(OH)D concentrations in a single laboratory minimized test level variations. Our current study formed the basis of further studies to determine if vitamin D deficiency and insufficiency can aggravate systemic diseases, including hypertension, diabetes or obesity that are also wide spread in the Middle Eastern region. PMID- 26877205 TI - Holding RIPK1 on the Ubiquitin Leash in TNFR1 Signaling. AB - The kinase RIPK1 is an essential signaling node in various innate immune signaling pathways being most extensively studied in the TNFR1 signaling pathway. TNF signaling can result in different biological outcomes including gene activation and cell death induction in the form of apoptosis or necroptosis. RIPK1 is believed to be crucial for regulating the balance between these opposing outcomes. It is therefore not surprising that RIPK1 is highly regulated, most notably by phosphorylation, ubiquitination, and their respective reversals. In this review, we discuss the biological functions of RIPK1 within the context of TNFR1 signaling. Finally, we discuss recent advances in the knowledge on three ubiquitin E3 ligases that exert regulatory functions on RIPK1 signaling: cIAP1, cIAP2, and LUBAC. PMID- 26877206 TI - Effectiveness of hand hygiene depends on the patient's health condition and care environment. AB - AIM: The present authors examined how patient hand contamination was associated with underlying disease and treatment environment in order to determine effective hand hygiene methods. METHODS: Samples were collected from inpatients (45 with hematological malignancies, 48 postoperative), outpatients (48 undergoing hemodialysis, 55 on chemotherapy), and 44 individuals living in nursing homes. All participants provided informed consent for study participation. All subjects performed hand hygiene. Before and after hand hygiene, samples of bacteria were collected from the palm of the hand onto agar media. Bacteria were counted and bacterial strains were identified. The authors then collected smear samples from the contralateral palm and measured adenosine triphosphate (ATP) levels. RESULTS: Patient hand contamination was the highest in hemodialysis patients, followed by residents of nursing homes, postoperative patients, patients with cancer receiving chemotherapy, and patients of hematological malignancies. Regardless of the underlying disease and treatment environment, patients were able to reduce the number of bacterial colonies and ATP by proper hand hygiene. Compared with wet wipes, hand washing seemed to remove bacteria more effectively. Methicillin resistant Staphylococcus aureus (MRSA) was detected in 30 subjects, none of whom were patients of hematological malignancies. Of these, 19 tested negative for MRSA after performing proper hand hygiene. CONCLUSION: Patient hand contamination is affected by underlying disease and care environment, but can be reduced by encouraging proper hand washing. Proper patient hand hygiene can reduce MRSA on patients' hands, and thus may serve as an effective tool for prevention of healthcare-associated infections. PMID- 26877207 TI - Variational bayesian method of estimating variance components. AB - We developed a Bayesian analysis approach by using a variational inference method, a so-called variational Bayesian method, to determine the posterior distributions of variance components. This variational Bayesian method and an alternative Bayesian method using Gibbs sampling were compared in estimating genetic and residual variance components from both simulated data and publically available real pig data. In the simulated data set, we observed strong bias toward overestimation of genetic variance for the variational Bayesian method in the case of low heritability and low population size, and less bias was detected with larger population sizes in both methods examined. The differences in the estimates of variance components between the variational Bayesian and the Gibbs sampling were not found in the real pig data. However, the posterior distributions of the variance components obtained with the variational Bayesian method had shorter tails than those obtained with the Gibbs sampling. Consequently, the posterior standard deviations of the genetic and residual variances of the variational Bayesian method were lower than those of the method using Gibbs sampling. The computing time required was much shorter with the variational Bayesian method than with the method using Gibbs sampling. PMID- 26877204 TI - Evolutionary Turnover of Kinetochore Proteins: A Ship of Theseus? AB - The kinetochore is a multiprotein complex that mediates the attachment of a eukaryotic chromosome to the mitotic spindle. The protein composition of kinetochores is similar across species as divergent as yeast and human. However, recent findings have revealed an unexpected degree of compositional diversity in kinetochores. For example, kinetochore proteins that are essential in some species have been lost in others, whereas new kinetochore proteins have emerged in other lineages. Even in lineages with similar kinetochore composition, individual kinetochore proteins have functionally diverged to acquire either essential or redundant roles. Thus, despite functional conservation, the repertoire of kinetochore proteins has undergone recurrent evolutionary turnover. PMID- 26877208 TI - Feasible logic Bell-state analysis with linear optics. AB - We describe a feasible logic Bell-state analysis protocol by employing the logic entanglement to be the robust concatenated Greenberger-Horne-Zeilinger (C-GHZ) state. This protocol only uses polarization beam splitters and half-wave plates, which are available in current experimental technology. We can conveniently identify two of the logic Bell states. This protocol can be easily generalized to the arbitrary C-GHZ state analysis. We can also distinguish two N-logic-qubit C GHZ states. As the previous theory and experiment both showed that the C-GHZ state has the robustness feature, this logic Bell-state analysis and C-GHZ state analysis may be essential for linear-optical quantum computation protocols whose building blocks are logic-qubit entangled state. PMID- 26877210 TI - Laparoscopic sacrocolpopexy: how low does the mesh go? AB - OBJECTIVE: Laparoscopic sacrocolpopexy is becoming an increasingly popular surgical approach for repair of apical vaginal prolapse. The aim of this study was to document the postoperative anterior mesh position after laparoscopic sacrocolpopexy and to investigate the relationship between mesh location and anterior compartment support. METHODS: This was an external audit of patients who underwent laparoscopic sacrocolpopexy for apical prolapse >= Stage 2 or advanced prolapse >= Stage 3, between January 2005 and June 2012. All patients were assessed with a standardized interview, clinical assessment using the International Continence Society Pelvic Organ Prolapse quantification and four dimensional transperineal ultrasound to evaluate pelvic organ support and mesh location. Mesh position was assessed with respect to the symphysis pubis whilst distal mesh mobility was assessed using the formula ?[(XValsalva - Xrest )2 + (YValsalva - Yrest )2 ], where X is the horizontal distance and Y is the vertical distance between the mesh and the inferior symphyseal margin, measured at rest and on Valsalva. RESULTS: Ninety-seven women were assessed at a mean follow-up of 3.01 (range, 0.13-6.87) years after laparoscopic sacrocolpopexy, 88% (85/97) of whom considered themselves to be cured or improved, and none had required reoperation. On clinical examination, prolapse recurrence in the apical compartment was not diagnosed in any patient; however, 60 (62%) had recurrence in the anterior compartment and 43 (44%) in the posterior compartment. On ultrasound examination, mesh was visualized in the anterior compartment in 60 patients. Both mesh position and mobility on Valsalva were significantly associated with recurrent cystocele on clinical and on ultrasound assessment (all P < 0.01). For every mm that the mesh was located further from the bladder neck on Valsalva, the likelihood of cystocele recurrence increased by 6-7%. CONCLUSION: At an average follow-up of 3 years, laparoscopic sacrocolpopexy was highly effective for apical support; however, cystocele recurrence was common despite an emphasis on anterior mesh extension. Prolapse recurrence seemed to be related to mesh position and mobility, suggesting that the lower the mesh is from the bladder neck, the lower the likelihood of anterior compartment prolapse recurrence. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26877211 TI - Apolipoprotein E genotype is not associated with cognitive impairment in older adults with bipolar disorder. AB - OBJECTIVES: Cognitive decline is part of the long-term outcome for many individuals with bipolar disorder (BD). The epsilon4 allele (APOE*4) of apolipoprotein E (APOE) is a well-established risk factor for dementia in Alzheimer's disease (AD). However, its contribution to the risk of cognitive deterioration in BD has not yet been determined. Our aim was to analyze the APOE genotype association with cognitive status in a sample of older adults with BD and compare this to the association in individuals with AD, individuals with mild cognitive impairment (MCI), and healthy controls. METHODS: Participants (n = 475) were allocated to four groups: individuals with BD (n = 77), those with AD (n = 211), those with MCI (n = 43), and healthy controls (n = 144) according to clinical and neuropsychological assessment. APOE was genotyped by real-time polymerase chain reaction. Tukey's honest significant difference test and Pearson's chi-squared test were used to compare diagnostic groups. RESULTS: Subjects with BD were similar to controls with respect to the distribution of the APOE genotype (p = 0.636) and allele frequencies (p = 0.481). Significant differences were found when comparing the AD group to the BD group or to controls (APOE genotype: p < 0.0002; allele frequencies: p < 0.001). APOE*4 was significantly increased in the AD group when compared to the BD group (p = 0.031) and controls (p < 0.0001). The cognitively impaired BD subgroup (Mini-Mental State Examination below the cutoff score and/or neuropsychological assessment compatible with MCI) had a statistically significant higher frequency of APOE*2 compared to the AD group (p = 0.003). CONCLUSIONS: APOE*4 is not associated with the diagnosis of BD and does not impact the occurrence of dementia in BD. Given the distinct clinical and biological features of cognitive impairment in BD, we hypothesized that dementia in BD is unrelated to AD pathological mechanisms. PMID- 26877212 TI - In defense of the History and Humanities in Ophthalmology. PMID- 26877209 TI - Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote. AB - Hydrogen sulfide is a highly toxic gas-second only to carbon monoxide as a cause of inhalational deaths. Its mechanism of toxicity is only partially known, and no specific therapy exists for sulfide poisoning. We show in several cell types, including human inducible pluripotent stem cell (hiPSC)-derived neurons, that sulfide inhibited complex IV of the mitochondrial respiratory chain and induced apoptosis. Sulfide increased hydroxyl radical production in isolated mouse heart mitochondria and F2-isoprostanes in brains and hearts of mice. The vitamin B12 analog cobinamide reversed the cellular toxicity of sulfide, and rescued Drosophila melanogaster and mice from lethal exposures of hydrogen sulfide gas. Cobinamide worked through two distinct mechanisms: direct reversal of complex IV inhibition and neutralization of sulfide-generated reactive oxygen species. We conclude that sulfide produces a high degree of oxidative stress in cells and tissues, and that cobinamide has promise as a first specific treatment for sulfide poisoning. PMID- 26877213 TI - Energy metabolism in neuronal/glial induction and in iPSC models of brain disorders. AB - The metabolic switch associated with the reprogramming of somatic cells to pluripotency has received increasing attention in recent years. However, the impact of mitochondrial and metabolic modulation on stem cell differentiation into neuronal/glial cells and related brain disease modeling still remains to be fully addressed. Here, we seek to focus on this aspect by first addressing brain energy metabolism and its inter-cellular metabolic compartmentalization. We then review the findings related to the mitochondrial and metabolic reconfiguration occurring upon neuronal/glial specification from pluripotent stem cells (PSCs). Finally, we provide an update of the PSC-based models of mitochondria-related brain disorders and discuss the challenges and opportunities that may exist on the road to develop a new era of brain disease modeling and therapy. PMID- 26877214 TI - The influence of negative urgency, attentional bias, and emotional dimensions on palatable food consumption. AB - We tested a theoretical model concerning the role of attentional bias and negative affect in food consumption that offers important advances. We hypothesized that the effects of negative affect manipulations on food consumption vary as a function of trait levels of negative urgency (NU; tendency to act impulsively when distressed), and attentional bias and that the roles of emotional arousal and negative emotional valence differ and should be studied separately. 190 undergraduate women were randomly assigned to either an anger or neutral mood condition. Women in both conditions completed the Food Stroop, in which the presentation of food and neutral words were counterbalanced. After the task, participants were given the opportunity to eat mandarin oranges and/or chocolate candy while the experimenter was out of the room. The type and quantity of food consumed was counted after the participant departed. As hypothesized, the roles of emotional arousal and valence differed and the effect of the induced emotion was moderated by NU. Women high in NU who experienced emotional arousal were more likely to eat candy and consumed more candy than other women. Emotional valence had no effect on candy consumption. Neither increases in emotional arousal or emotional valence influenced attentional bias to food cues. Attentional bias was also unrelated to food consumption. The impact of negative mood inductions on palatable food consumption appears to operate through emotional arousal and not negative emotional valence, and it may operate primarily for women high in NU. PMID- 26877215 TI - Obesity, food restriction, and implicit attitudes to healthy and unhealthy foods: Lessons learned from the implicit relational assessment procedure. AB - It has been argued that obese individuals evaluate high caloric, palatable foods more positively than their normal weight peers, and that this positivity bias causes them to consume such foods, even when healthy alternatives are available. Yet when self-reported and automatic food preferences are assessed no such evaluative biases tend to emerge. We argue that situational (food deprivation) and methodological factors may explain why implicit measures often fail to discriminate between the food-evaluations of these two groups. Across three studies we manipulated the food deprivation state of clinically obese and normal weight participants and then exposed them to an indirect procedure (IRAP) and self-report questionnaires. We found that automatic food-related cognition was moderated by a person's weight status and food deprivation state. Our findings suggest that the diagnostic and predictive value of implicit measures may be increased when (a) situational moderators are taken into consideration and (b) we pay greater attention to the different ways in which people automatically relate rather than simply categorize food stimuli. PMID- 26877216 TI - Weight discrimination and unhealthy eating-related behaviors. AB - Individuals with obesity often experience unfair treatment because of their body weight. Such experiences are associated with binge eating, but less is known about its association with other eating-related behaviors and whether these relations are specific to discrimination based on weight or extend to other attributions for discrimination. The present research uses a large national sample (N = 5129) to examine whether weight discrimination is associated with diet and meal rhythmicity, in addition to overeating, and whether these associations generalize to nine other attributions for discrimination. We found that in addition to overeating, weight discrimination was associated with more frequent consumption of convenience foods and less regular meal timing. These associations were generally similar across sex, age, and race. Discrimination based on ancestry, gender, age, religion, and physical disability were also associated with overeating, which suggests that overeating may be a general coping response to discrimination. Unfair treatment because of body weight is associated with unhealthy eating-related behaviors, which may be one pathway through which weight discrimination increases risk for weight gain and obesity. PMID- 26877217 TI - Functional Imagery Training to reduce snacking: Testing a novel motivational intervention based on Elaborated Intrusion theory. AB - Functional Imagery Training (FIT) is a new theory-based, manualized intervention that trains positive goal imagery. Multisensory episodic imagery of proximal personal goals is elicited and practised, to sustain motivation and compete with less functional cravings. This study tested the impact of a single session of FIT plus a booster phone call on snacking. In a stepped-wedge design, 45 participants who wanted to lose weight or reduce snacking were randomly assigned to receive a session of FIT immediately or after a 2-week delay. High-sugar and high-fat snacks were recorded using timeline follow back for the previous 3 days, at baseline, 2 and 4 weeks. At 2 weeks, snacking was lower in the immediate group than in the delayed group, and the reduction after FIT was replicated in the delayed group between 2 and 4 weeks. Frequencies of motivational thoughts about snack reduction rose following FIT for both groups, and this change correlated with reductions in snacking and weight loss. By showing that FIT can support change in eating behaviours, these findings show its potential as a motivational intervention for weight management. PMID- 26877218 TI - Weight-related teasing and non-normative eating behaviors as predictors of weight loss maintenance. A longitudinal mediation analysis. AB - Weight loss maintenance is essential for the reduction of obesity-related health impairments. However, only a minority of individuals successfully maintain reduced weight in the long term. Research has provided initial evidence for associations between weight-related teasing (WRT) and greater non-normative eating behaviors. Further, first evidence was found for associations between non normative eating behaviors and weight loss maintenance. Hence, the present study aimed to examine the predictive value of WRT for weight loss maintenance and the role of non-normative eating behaviors as possible mediators of this relationship. The study was part of the German Weight Control Registry that prospectively followed individuals who had intentionally lost at least 10% of their maximum weight and had maintained this reduced weight for at least one year. In N = 381 participants, retrospective WRT during childhood and adolescence, current non-normative eating behaviors (i.e., restrained, external, emotional eating), and change in body mass index (BMI, kg/m(2)) over two years were examined using self-report assessments. Structural equation modeling was used to analyze the assumed mediational relationship. As a result, a greater effect of retrospective WRT during childhood and adolescence predicted less successful adult weight loss maintenance over two years. Current emotional eating fully mediated this relationship while current restrained and external eating yielded no mediational effects. Hence, a greater effect of WRT predicted greater current emotional eating, which in turn predicted a smaller decrease or a greater increase in BMI. Our findings suggest that suffering from WRT during childhood and adolescence might lead to emotional eating which in turn impairs long-term weight loss maintenance. Thus, our results highlight the need for interventions aiming at reducing weight stigmatization and targeting emotional eating for successful long-term weight loss maintenance. PMID- 26877219 TI - Morphine sulfate concomitantly decreases neuronal differentiation and opioid receptor expression in mouse embryonic stem cells. AB - Opioids have been shown to affect prenatal and postnatal neural development in mammals. The present study investigates the impact of morphine sulfate (MS) treatment on neuronal differentiation as well as MU-opioid receptor (MOR) expression in mouse embryonic stem (mES) cells. Stem cells were manipulated in culture to differentiate in 3 sequential stages: Stage 1, cell transformation to embryoid bodies (EB); Stage 2, EB cell differentiation to neural progenitor (NP) cells; and, Stage 3, NP cell differentiation to neurons/astrocytes co-cultured cells. Using RT-PCR and flow cytometry analyses, cell types were confirmed by monitoring expression of Oct4, nestin, microtubule-associated protein 2 (mtap-2), and glial fibrillary acidic protein (GFAP) as cell-specific markers for stem cells, NP cells, neurons, and astrocytes, respectively. Similarly, gene expression for MOR, kappa-opioid receptor (KOR), and delta-opioid receptor (DOR) was confirmed in each cell type. In order to investigate the effects of MS on differentiation, cells were treated with MS (1, 10, 100 MUM) at either early (Stage 1) or late (Stage 3) stage of cellular differentiation. At Stage 1 exposure, MOR gene expression and neuroectoderm specific marker expression of nestin were down-regulated in both EB and NP cells. In addition, the opioid down regulated GFAP in differentiated neurons/astrocytes co-cultured cells. Late stage treatment with MS resulted in a down-regulation of mtap-2 and GFAP in differentiated neurons/astrocytes co-cultured cells. Moreover, late stage treatment with MS and naltrexone inhibited the effect of MS on neuronal differentiation, suggesting that MS treatment interferes with differentiation via MOR activation. Together, the results show that MS exposure at early and late stage of cellular differentiation significantly decreases genotype and phenotype in differentiated neuronal cells. The results of this study have implications regarding the potential effect of opiates on fetal brain development. PMID- 26877220 TI - Low-level lead exposure and autistic behaviors in school-age children. AB - INTRODUCTION: The association between lead exposure and autism spectrum disorder is inconclusive. We hypothesized an association between higher blood lead concentrations and more autistic behaviors, including impaired social interactions and communication, stereotypical behaviors, and restricted interests, among school-age children. METHODS: Data from 2473 Korean children aged 7-8years who had no prior history of developmental disorders were analyzed. Two follow-up surveys were conducted biennially until the children reached 11 12years of age. Blood lead concentrations were measured at every survey, and autistic behaviors were evaluated at 11-12years of age using the Autism Spectrum Screening Questionnaire (ASSQ) and Social Responsiveness Scale (SRS). The associations of blood lead concentration with ASSQ and SRS scores were analyzed using negative binomial, logistic, and linear regression models. RESULTS: Blood lead concentrations at 7-8years of age (geometric mean: 1.64MUg/dL), but not at 9 10 and 11-12years of age, were associated with more autistic behaviors at 11 12years of age, according to the ASSQ (beta=0.151; 95% confidence interval [CI]: 0.061, 0.242) and SRS (beta=2.489; 95% CI: 1.378, 3.600). SRS subscale analysis also revealed associations between blood lead concentrations and social awareness, cognition, communication, motivation, and mannerisms. CONCLUSION: Even low blood lead concentrations at 7-8years of age are associated with more autistic behaviors at 11-12years of age, underscoring the need for continued efforts to reduce lead exposure. PMID- 26877221 TI - Time and dose dependent effects of oxidative stress induced by cumene hydroperoxide in neuronal excitability of rat motor cortex neurons. AB - It has been claimed that oxidative stress and the production of reactive oxygen radicals can contribute to neuron degeneration and might be one factor in the development of different neurological diseases. In our study, we have attempted to clarify how oxidative damage induces dose dependent changes in functional membrane properties of neurons by means of whole cell patch clamp techniques in brain slices from young adult rats. Our research demonstrates physiological changes in membrane properties of pyramidal motor cortex neurons exposed to 3 concentrations of cumene hydroperoxide (CH; 1, 10 and 100MUM) during 30min. Results show that oxidative stress induced by CH evokes important changes, in a concentration and time dependent manner, in the neuronal excitability of motor cortex neurons of the rat: (i) Low concentration of the drug (1MUM) already blocks inward rectifications (sag) and decreases action potential amplitude and gain, a drug concentration which has no effects on other neuronal populations, (ii) 10MUM of CH depresses the excitability of pyramidal motor cortex neurons by decreasing input resistance, amplitude of the action potential, and gain and maximum frequency of the repetitive firing discharge, and (iii) 100MUM completely blocks the capability to produce repetitive discharge of action potentials in all cells. Both larger drug concentrations and/or longer times of exposure to CH narrow the current working range. This happens because of the increase in the rheobase, and the reduction of the cancelation current. The effects caused by oxidative stress, including those produced by the level of lipid peroxidation, are practically irreversible and, this, therefore, indicates that neuroprotective agents should be administered at the first symptoms of alterations to membrane properties. In fact, the pre-treatment with melatonin, acting as an antioxidant, prevented the lipid peroxidation and the physiological changes induced by CH. Larger cells (as estimated by their cell capacitance) were also more susceptible to oxidative stress. Our results provide previously unavailable observations that large size and high sensitivity to oxidative stress (even at low concentrations) make pyramidal neurons of the motor cortex, in particular corticofugal neurons, more susceptible to cell death when compared with other neuronal populations. These results could also shed some light on explaining the causes behind diseases such as Amyotrophic Lateral Sclerosis. PMID- 26877222 TI - The importance of fetal sex determination. PMID- 26877223 TI - Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors. AB - Several studies have reported reprogramming of fibroblasts into induced cardiomyocytes; however, reprogramming into proliferative induced cardiac progenitor cells (iCPCs) remains to be accomplished. Here we report that a combination of 11 or 5 cardiac factors along with canonical Wnt and JAK/STAT signaling reprogrammed adult mouse cardiac, lung, and tail tip fibroblasts into iCPCs. The iCPCs were cardiac mesoderm-restricted progenitors that could be expanded extensively while maintaining multipotency to differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells in vitro. Moreover, iCPCs injected into the cardiac crescent of mouse embryos differentiated into cardiomyocytes. iCPCs transplanted into the post-myocardial infarction mouse heart improved survival and differentiated into cardiomyocytes, smooth muscle cells, and endothelial cells. Lineage reprogramming of adult somatic cells into iCPCs provides a scalable cell source for drug discovery, disease modeling, and cardiac regenerative therapy. PMID- 26877225 TI - Visualising the molecular alteration of the calcite (104) - water interface by sodium nitrate. AB - The reactivity of calcite, one of the most abundant minerals in the earth's crust, is determined by the molecular details of its interface with the contacting solution. Recently, it has been found that trace concentrations of NaNO3 severely affect calcite's (104) surface and its reactivity. Here we combine molecular dynamics (MD) simulations, X-ray reflectivity (XR) and in situ atomic force microscopy (AFM) to probe the calcite (104) - water interface in the presence of NaNO3. Simulations reveal density profiles of different ions near calcite's surface, with NO3(-) able to reach closer to the surface than CO3(2-) and in higher concentrations. Reflectivity measurements show a structural destabilisation of the (104) surfaces' topmost atomic layers in NaNO3 bearing solution, with distorted rotation angles of the carbonate groups and substantial displacement of the lattice ions. Nanoscale AFM results confirm the alteration of crystallographic characteristics, and the ability of dissolved NaNO3 to modify the structure of interfacial water was observed by AFM force spectroscopy. Our experiments and simulations consistently evidence a dramatic deterioration of the crystals' surface, with potentially important implications for geological and industrial processes. PMID- 26877224 TI - A Single CRISPR-Cas9 Deletion Strategy that Targets the Majority of DMD Patients Restores Dystrophin Function in hiPSC-Derived Muscle Cells. AB - Mutations in DMD disrupt the reading frame, prevent dystrophin translation, and cause Duchenne muscular dystrophy (DMD). Here we describe a CRISPR/Cas9 platform applicable to 60% of DMD patient mutations. We applied the platform to DMD derived hiPSCs where successful deletion and non-homologous end joining of up to 725 kb reframed the DMD gene. This is the largest CRISPR/Cas9-mediated deletion shown to date in DMD. Use of hiPSCs allowed evaluation of dystrophin in disease relevant cell types. Cardiomyocytes and skeletal muscle myotubes derived from reframed hiPSC clonal lines had restored dystrophin protein. The internally deleted dystrophin was functional as demonstrated by improved membrane integrity and restoration of the dystrophin glycoprotein complex in vitro and in vivo. Furthermore, miR31 was reduced upon reframing, similar to observations in Becker muscular dystrophy. This work demonstrates the feasibility of using a single CRISPR pair to correct the reading frame for the majority of DMD patients. PMID- 26877226 TI - Prevalence and genetic analysis of alpha- and beta-thalassemia in Baise region, a multi-ethnic region in southern China. AB - Thalassemia is one of the most common hereditary blood disorders. Epidemiological data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies. The objective of this study was to update and reveal the prevalence of thalassemia and mutation spectrum in the Baise region of southern China. We screened 47,500 individuals from Baise region by hematological and genetic analysis. Totally, 11,432 (24.07%) subjects were diagnosed as being carriers and patients of thalassemia, including 7290 (15.35%) subjects with alpha-thalassemia, 3152 (6.64%) subjects with beta-thalassemia and 990 (2.08%) subjects with both alpha-thalassemia and beta-thalassemia. Ten alpha thalassemia mutations and 31 genotypes were identified in the alpha-thalassemia carriers and patients. Meanwhile, 13 beta-thalassemia mutations and 26 genotypes were characterized in the beta-thalassemia carriers and patients. Furthermore, the true prevalence of nondeletional mutations and Thailand type (-THAI) deletion mutation were first reported in this study. In addition, three cases of alphaalpha/alphaalphaalpha3.7, five cases of HKalphaalpha/alphaalpha and two rare beta-globin mutations, -86 (G>C) and CD 121 (G>T) were first identified in the Chinese Zhuang ethnic populations. Our data indicated that there was great heterogeneity and extensive spectrum of thalassemias in the Baise populations. The findings will be useful for genetic counseling and prevention of severe thalassemia in this region. PMID- 26877227 TI - Application of Euclidean distance measurement and principal component analysis for gene identification. AB - Gene systems are extremely complex, heterogeneous, and noisy in nature. Many statistical tools which are used to extract relevant feature from genes provide fuzzy and ambiguous information. High-dimensional gene expression database available in public domain usually contains thousands of genes. Efficient prediction method is demanding nowadays for accurate identification of such database. Euclidean distance measurement and principal component analysis methods are applied on such databases to identify the genes. In both methods, prediction algorithm is based on homology search approach. Digital Signal Processing technique along with statistical method is used for analysis of genes in both cases. A two-level decision logic is used for gene classification as healthy or cancerous. This binary logic minimizes the prediction error and improves prediction accuracy. Superiority of the method is judged by receiver operating characteristic curve. PMID- 26877228 TI - The association between discrepant weight perceptions and objectively measured physical activity. AB - BACKGROUND: Some individuals perceive themselves as being normal weight, despite having an excess body fat percentage (e.g., underestimate weight). Conversely, other individuals perceive themselves as being overweight, despite having a normal body fat percentage (e.g., overestimate weight). When perceived and actual weight statuses are incongruent, individuals possess a discrepant weight perception. The association between discrepant weight perceptions and engagement in moderate-to-vigorous physical activity (MVPA) has not been thoroughly investigated, which was this study's purpose. METHODS: For this cross-sectional study, data from the 2003-2006 National Health and Nutrition Examination Survey were utilized (N=5462 adults). MVPA was assessed via accelerometry. Based on measured body mass index and whether participants considered themselves as overweight, underweight, or about the right weight, we classified individuals as accurate perception, overestimate weight (discrepant), or underestimate weight (discrepant). A negative binomial logistical regression was used to assess the association between discrepant weight perception (independent variable) and engagement in MVPA (outcome variable). RESULTS: Females who said that they are normal weight, but were in fact overweight based on body mass index, engaged in 13% less MVPA (rate ratio=.87, 95% confidence interval: .769-.999, P=.05). Also, older adults (>60yrs) who said that they are normal weight, but were overweight based on body mass index, engaged in 23% less MVPA (rate ratio=.77, 95% confidence interval: .616-.965, P=.025). CONCLUSION: Discrepant weight perceptions were associated with less objectively measured MVPA. Interventions should take weight perceptions into consideration when designing and evaluating intervention impact. PMID- 26877230 TI - Surface-induced phase transitions of wormlike chains in slit confinement. AB - On the basis of a self-consistent field theory treatment of semi-flexible polymer chains, we analyze the effects of the flexibility on the structure of polymers sterically confined between two parallel, structureless walls separated by a distance. The model is built from a wormlike chain formalism which crosses over from the rod limit to the flexible limit, and the Onsager-type interaction which describes the orientation-dependent excluded-volume interaction. Three surface states were obtained from the numerical solution to the theory: uniaxial, biaxial, and condensed. As the overall density increases in such a lyotropic system, first order phase transitions between uniaxial and biaxial states, biaxial and condensed states can occur. PMID- 26877229 TI - Disentangling visual and olfactory signals in mushroom-mimicking Dracula orchids using realistic three-dimensional printed flowers. AB - Flowers use olfactory and visual signals to communicate with pollinators. Disentangling the relative contributions and potential synergies between signals remains a challenge. Understanding the perceptual biases exploited by floral mimicry illuminates the evolution of these signals. Here, we disentangle the olfactory and visual components of Dracula lafleurii, which mimics mushrooms in size, shape, color and scent, and is pollinated by mushroom-associated flies. To decouple signals, we used three-dimensional printing to produce realistic artificial flower molds that were color matched and cast using scent-free surgical silicone, to which we could add scent. We used GC-MS to measure scents in co-occurring mushrooms, and related orchids, and used these scents in field experiments. By combining silicone flower parts with real floral organs, we created chimeras that identified the mushroom-like labellum as a source of volatile attraction. In addition, we showed remarkable overlap in the volatile chemistry between D. lafleurii and co-occurring mushrooms. The characters defining the genus Dracula - a mushroom-like, 'gilled' labellum and a showy, patterned calyx - enhance pollinator attraction by exploiting the visual and chemosensory perceptual biases of drosophilid flies. Our techniques for the manipulation of complex traits in a nonmodel system not conducive to gene silencing or selective breeding are useful for other systems. PMID- 26877231 TI - New quantum spin Hall insulator in two-dimensional MoS2 with periodically distributed pores. AB - MoS2, one of the transition metal dichalcogenides (TMDs), has gained a lot of attention due to its excellent semiconductor characteristics and potential applications. Here, based on density functional theory methods, we predict a novel 2D QSH insulator in the porous allotrope of monolayer MoS2 (g-MoS2), consisting of MoS2 squares and hexagons. g-MoS2 has a nontrivial gap as large as 109 meV, comparable with previously reported 1T'-MoS2 (80 meV) and so-MoS2 (25 meV). We demonstrate that the origin of the 2D QSH effect in g-MoS2 originates from the pure d-d band inversion, different from the conventional band inversion between s-p, p-p or d-p orbitals. The new polymorph greatly enriches the TMD family and its stabilities are confirmed using phonon spectrum analysis. In particular, its porous structure endows it with the potential for efficient gas separation and energy storage applications. PMID- 26877232 TI - Extensive tumoral melanosis associated with ipilimumab-treated melanoma. AB - Tumoral melanosis describes a pigmented lesion clinically similar to melanoma but on histology reveals dense aggregates of melanin-laden, benign macrophages without malignant cells. In the few reported cases so far, tumoral melanosis has arisen in the skin or lymph node of a patient with a regressed melanoma or an epithelioid tumour. As a marker of regressed primary melanoma, its discovery may prompt investigation and surveillance for undiagnosed local or metastatic disease. Here, we present a unique case of extensive tumoral melanosis arising during ipilimumab treatment of in-transit metastases from a previously excised melanoma. PMID- 26877233 TI - [Greenlight((r)) photoselective vaporization of the prostate: Contemporary practices in France]. AB - INTRODUCTION: Photovaporization of the prostate by the Greenlight((r)) laser (GL) has been strongly developed this past few years in France, representing nearly 30% of surgery for BPH, making France the second GL user worldwide after USA. The objective of this study was to assess the French surgeons practices with the Greenlight((r)) laser. MATERIAL AND METHODS: During the 4th meeting of French Greenlight((r)) users group (GUGL), was proposed a questionnaire on the management of patients and the GL technique. The questionnaire covered the operator's characteristics (age, experience with the GL, etc.), the treatment strategy, preoperative management (anticoagulants...) and postoperative management (ambulatory, removal catheter...) as well as the surgical technique (fiber type, energy used, etc.). RESULTS: Among the 117 participants, 64 answered to the questionnaire (55%). Fifty-six percent chose GL, whatever was the prostate volume, simple prostatectomy was the most commonly alternative used for high prostate size (39%). The aspirin was pursued by 89% of practitioners perioperatively. Conversely, clopidogrel was continued by only 19% and anticoagulant by only 14%. Seventy-three percent of participants commonly used classic vaporization and only 3% used new techniques (GreenLEP). During procedure, 72% used energy between 120W and 160W. Sixty percent used transrectal ultrasound during surgery (32% throughout the procedure). Only 16% of surgeons made ambulatory procedure and almost 33% never. Surgeons with over 3years of experience (vs.<3years) used the technique regardless of the volume in 67% vs. 23.5% (P=0.002). CONCLUSION: In France Greenlight use is still heterogeneous for the patient's management. New techniques which are currently developing (GreenLEP, vapo-enucleation) are still marginal. Ambulatory is still insufficiently used and need to be developed. The experienced surgeon led to wider indication for the technique. LEVEL OF EVIDENCE: 3. PMID- 26877234 TI - [How to approach the proofreading of an article submitted to Progres en urologie? Opinion of the best reviewer in 2015]. PMID- 26877235 TI - Water-Soluble Compounds from Lentinula edodes Influencing the HMG-CoA Reductase Activity and the Expression of Genes Involved in the Cholesterol Metabolism. AB - A water extract from Lentinula edodes (LWE) showed HMG-CoA reductase inhibitory activity but contained no statins. NMR indicated the presence of water-soluble alpha- and beta-glucans and fucomannogalactans. Fractions containing derivatives of these polysaccharides with molecular weight down to approximately 1 kDa still retained their inhibitory activity. Once digested LWE was applied to Caco2 in transport experiments, no significant effect was noticed on the modulation of cholesterol-related gene expression. But, when the lower compartment of the Caco2 monolayer was applied to HepG2, some genes were modulated (after 24 h). LWE was also administrated to normo- and hypercholesterolemic mice, and no significant lowering of serum cholesterol levels was observed; but reduction of triglycerides in liver was observed. However, LWE supplementation modulated the transcriptional profile of some genes involved in the cholesterol metabolism similarly to simvastatin, suggesting that it could hold potential as a hypolipidemic/hypocholesterolemic extract, although further dose-dependent studies should be carried out. PMID- 26877236 TI - The Oct1 transcription factor and epithelial malignancies: Old protein learns new tricks. AB - The metazoan-specific POU domain transcription factor family comprises activities underpinning developmental processes such as embryonic pluripotency and neuronal specification. Some POU family proteins efficiently bind an 8-bp DNA element known as the octamer motif. These proteins are known as Oct transcription factors. Oct1/POU2F1 is the only widely expressed POU factor. Unlike other POU factors it controls no specific developmental or organ system. Oct1 was originally described to operate at target genes associated with proliferation and immune modulation, but more recent results additionally identify targets associated with oxidative and cytotoxic stress resistance, metabolic regulation, stem cell function and other unexpected processes. Oct1 is pro-oncogenic in multiple contexts, and several recent reports provide broad evidence that Oct1 has prognostic and therapeutic value in multiple epithelial tumor settings. This review focuses on established and emerging roles of Oct1 in epithelial tumors, with an emphasis on mechanisms of transcription regulation by Oct1 that may underpin these findings. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. PMID- 26877239 TI - Stimulated echo diffusion weighted imaging of the liver at 3 Tesla. AB - PURPOSE: Diffusion time (Delta) effect in diffusion measurements has been validated as a sensitive biomarker in liver fibrosis by rat models. To extend this finding to clinical study, a reliable imaging technique is highly desirable. This study aimed to develop an optimal stimulated echo acquisition mode (STEAM) diffusion-weighted imaging (DWI) method dedicated to human liver imaging on 3 Tesla (T) and preliminarily investigate the dependence effect in healthy volunteers. METHODS: STEAM DWI with single-shot echo planar imaging readout was used as it provided better signal-to-noise ratio (SNR) than spin echo DWI methods when a long Delta was needed for liver imaging. Additionally, a slice-selection gradient reversal method was used for fat suppression. Motion compensation and SNR improvement strategies were used to further improve the image quality. Five b values with three Deltas were tested in 10 volunteers. RESULTS: Effective fat suppression and motion compensation were reproducibly achieved in the optimized sequence. The signal decay generally became slower when the Deltas increased. Obvious reduction of diffusion coefficients was observed with increasing Deltas in the liver. CONCLUSION: The results verified the Delta dependence in diffusion measurements, indicating restricted diffusion in healthy human livers for the first time at 3T. This prepared STEAM DWI a potential technique for liver fibrotic studies in clinical practice. Magn Reson Med 77:300-309, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26877238 TI - Heme oxygenase-1 attenuates IL-1beta induced alteration of anabolic and catabolic activities in intervertebral disc degeneration. AB - Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL 1beta stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1beta. Induction of HO-1 also reversed the effect of IL-1beta on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. PMID- 26877237 TI - Mechanisms of xenobiotic receptor activation: Direct vs. indirect. AB - The so-called xenobiotic receptors (XRs) have functionally evolved into cellular sensors for both endogenous and exogenous stimuli by regulating the transcription of genes encoding drug-metabolizing enzymes and transporters, as well as those involving energy homeostasis, cell proliferation, and/or immune responses. Unlike prototypical steroid hormone receptors, XRs are activated through both direct ligand-binding and ligand-independent (indirect) mechanisms by a plethora of structurally unrelated chemicals. This review covers research literature that discusses direct vs. indirect activation of XRs. A particular focus is centered on the signaling control of the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), and the aryl hydrocarbon receptor (AhR). We expect that this review will shed light on both the common and distinct mechanisms associated with activation of these three XRs. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID- 26877240 TI - A CAPS-based binding assay provides semi-quantitative validation of protein-DNA interactions. AB - Investigation of protein-DNA interactions provides crucial information for understanding the mechanisms of gene regulation. Current methods for studying protein-DNA interactions, such as DNaseI footprinting or gel shift assays, involve labeling DNA with radioactive or fluorescent tags, making these methods costly, laborious, and potentially damaging to the environment. Here, we describe a novel cleaved amplified polymorphic sequence (CAPS)-based binding assay (CBA), which is a label-free method that can simplify the semi-quantitative validation of protein-DNA interactions. The CBA tests the interaction between a protein and its target DNA, based on the CAPS pattern produced due to differences in the accessibility of a restriction endonuclease site (intrinsic or artificial) in amplified DNA in the presence and absence of the protein of interest. Thus, the CBA can produce a semi-quantitative readout of the interaction strength based on the dose of the binding protein. We demonstrate the principle and feasibility of CBA using B3, MADS3 proteins and the corresponding RY or CArG-box containing DNAs. PMID- 26877241 TI - Adrenocortical function in cane toads from different environments. AB - The adrenocortical function of cane toads (Rhinella marina) exposed to different experimental procedures, as well as captured from different environments, was assessed by challenging the hypothalamic-pituitary-adrenal (HPA) axis. It was found that restriction stress as well as cannulation increased plasma corticosterone (B) levels for up to 12h. A single dose of dexamethasone (DEX 2mg/kg) significantly reduced B levels demonstrating its potential for use in the evaluation of the HPA axis in amphibia. We also demonstrate that 0.05 IU/g BW (im) of synthetic adrenocorticotropic hormone (ACTH) significantly increased plasma B levels in cane toads. Changes in size area of the cortical cells were positively associated with total levels of B after ACTH administration. We also found differences in adrenal activity between populations. This was assessed by a DEX-ACTH test. The animals captured from the field and maintained in captivity for one year at the animal house (AH) present the highest levels of total and free B after ACTH administration. We also found that animals from the front line of dispersion in Western Australia (WA) present the weakest adrenal response to a DEX-ACTH test. The animals categorized as long established in Queensland Australia (QL), and native in Mexico (MX), do not shown a marked difference in the HPA activity. Finally we found that in response to ACTH administration, females reach significantly higher levels of plasma B than males. For the first time the adrenocortical response in cane toads exposed to different experimental procedures, as well as from different populations was assessed systematically. PMID- 26877242 TI - Potential roles of suppressor of cytokine signaling in wound healing. AB - Wound healing is a dynamic process comprising three overlapping, highly orchestrated stages known as inflammation, proliferation and re epithelialization, and tissue remodeling. This complex process is regulated by numerous cytokines, with dysregulation of cytokine-induced signaling leading to impaired wound healing. Suppressor of cytokine signaling (SOCS) proteins are a family of eight intracellular proteins which may hold the potential to maintain homeostasis during wound healing through their negative feedback inhibition of cytokine signaling. To date, the roles of SOCS proteins in inflammation, autoimmunity and cancer have been comprehensively illustrated; however, only a limited number of studies focused on their role in wound healing. This review demonstrates the possible links between SOCS proteins and wound healing, and also highlights the potential importance of this family in a variety of other aspects of regenerative medicine. PMID- 26877243 TI - Type I/II Interferon Balance in the Regulation of Brain Physiology and Pathology. AB - Recent findings have revealed distinct roles for type I and II interferons (IFN-I and IFN-gamma) in the recruitment of immune cells to the central nervous system (CNS) and highlighted the importance of this process for brain maintenance and protection/repair. Furthermore, manipulation of IFN-I and IFN-gamma pathways in pathological contexts has yielded conflicting results. We discuss these findings, focusing on two distinct conditions; relapsing remitting multiple sclerosis (RRMS) and brain aging. Using these examples, we propose that regulation of immune cell entry to the CNS is a mechanism through which interaction between IFN I and -II can affect brain function from its anatomical borders. Deviation from homeostatic IFN-I/-II balance may contribute to distinct brain pathologies, resulting from either insufficient immune surveillance of the CNS and loss of immune-dependent protection, or overwhelming leukocyte entry and immune-mediated destruction. PMID- 26877244 TI - Drug testing and flow cytometry analysis on a large number of uniform sized tumor spheroids using a microfluidic device. AB - Three-dimensional (3D) tumor spheroid possesses great potential as an in vitro model to improve predictive capacity for pre-clinical drug testing. In this paper, we combine advantages of flow cytometry and microfluidics to perform drug testing and analysis on a large number (5000) of uniform sized tumor spheroids. The spheroids are formed, cultured, and treated with drugs inside a microfluidic device. The spheroids can then be harvested from the device without tedious operation. Due to the ample cell numbers, the spheroids can be dissociated into single cells for flow cytometry analysis. Flow cytometry provides statistical information in single cell resolution that makes it feasible to better investigate drug functions on the cells in more in vivo-like 3D formation. In the experiments, human hepatocellular carcinoma cells (HepG2) are exploited to form tumor spheroids within the microfluidic device, and three anti-cancer drugs: Cisplatin, Resveratrol, and Tirapazamine (TPZ), and their combinations are tested on the tumor spheroids with two different sizes. The experimental results suggest the cell culture format (2D monolayer vs. 3D spheroid) and spheroid size play critical roles in drug responses, and also demonstrate the advantages of bridging the two techniques in pharmaceutical drug screening applications. PMID- 26877245 TI - Prevalence, risk factors and genetic parameters of cresty neck in Pura Raza Espanol horses. AB - REASONS FOR PERFORMING STUDY: Cresty neck is a relatively common morphological defect in Pura Raza Espanol horses and other Baroque type horse breeds, which adversely affects the breeding industry. OBJECTIVES: To establish the within breed prevalence, possible associated factors and heritability of cresty neck in Pura Raza Espanol horses. STUDY DESIGN: Cross-sectional analysis of a large worldwide database of Pura Raza Espanol horses. METHODS: The database included evaluations of 10,929 Pura Raza Espanol horses from 24 countries. Cresty neck score, on a 9 point scale, girth-to-height ratio, height at the withers, length of neck, head-neck junction and neck-body junction were recorded. A Bayesian genetic animal model included the following systematic effects: girth-to-height ratio, age, sex, coat colour and geographical area of the stud. Animal and residual effects were included as random effects. RESULTS: Within this Pura Raza Espanol population, 8.91% had a cresty neck score >=5, which is the threshold for penalty or disqualification in the studbook of the breed. The age, sex, coat colour and stud geographical area were significantly associated with cresty neck score. The estimated heritability coefficient for cresty neck score was 0.37 (s.d. = 0.034) and genetic correlation between cresty neck score and other conformational traits ranged from -0.06 (height-at-withers) to -0.21 (neck-body junction). CONCLUSIONS: Cresty neck is a prevalent defect in Pura Raza Espanol horses, associated with age, sex, coat colour and other conformational traits, with a moderate level of heritability. Breeding to select against this condition may therefore be beneficial in this breed. PMID- 26877246 TI - Persistent Organic Nanopores Amenable to Structural and Functional Tuning. AB - Rigid macrocycles 2, which share a hybrid backbone and the same set of side chains while having inner cavities with different inward-pointing functional groups, undergo similar nanotubular assembly as indicated by multiple techniques including (1)H NMR, fluorescence spectroscopy, and atomic force microscopy. The formation of tubular assemblies containing subnanometer pores is also attested by the different transmembrane ion-transport behavior observed for these macrocycles. Vesicle-based stopped-flow kinetic assay and single-channel electrophysiology with planar lipid bilayers show that the presence of an inward pointing functional (X) group in the inner cavity of a macrocyclic building block exerts a major influence on the transmembrane ion-transporting preference of the corresponding self-assembling pore. Self-assembling pores with inward-pointing amino and methyl groups possess the surprising and remarkable capability of rejecting protons but are conducive to transporting larger ions. The inward pointing groups also resulted in transmembrane pores with a different extent of positive electrostatic potentials, leading to channels having different preferences for transporting chloride ion. Results from this work demonstrate that synthetic modification at the molecular level can profoundly impact the property of otherwise structurally persistent supramolecular assemblies, with both expected tunability and suprisingly unusual behavior. PMID- 26877247 TI - Kinetic target-guided synthesis in drug discovery and chemical biology: a comprehensive facts and figures survey. AB - For the last 15 years, kinetic target-guided syntheses, including in situ click chemistry, have been used as alternative methods to find ligands to therapeutically relevant proteins. In this review, a comprehensive survey of biological targets used in kinetic target-guided synthesis covers historical and recent examples. The chemical reactions employed and practical aspects, including controls, library sizes and product detection, are presented. A particular focus is on the reagents and warhead selection and design with a critical overview of the challenges encountered. As protein supply remains a key success factor, it appears that increased efforts should be taken toward miniaturization in order to expand the scope of this strategy and qualify it as a fully fledged drug discovery tool. PMID- 26877249 TI - Erratum: Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection. PMID- 26877248 TI - Risk Factors for Steatorrhea in Chronic Pancreatitis: A Cohort of 2,153 Patients. AB - This study aimed to investigate the occurrence of and determine the risk factors for steatorrhea in chronic pancreatitis (CP). It was based on analysis of both retrospectively and prospectively acquired database for CP patients admitted to our center from January 2000 to December 2013. Demographic data, course of disease, medical history, and follow-up evaluations of patients were documented in detail. Cumulative rate of steatorrhea was calculated by using the Kaplan Meier method. For risk factor analysis, multivariate analysis by Cox proportional hazards regression model was performed. A total of 2,153 CP patients were included with a mean follow-up duration of 9.3 years. Approximately 14% (291/2,153) of CP patients presented with steatorrhea at diagnosis of CP. Cumulative rates of steatorrhea at 1, 5, 10, and 20 years after diagnosis of CP were 4.27% (95% CI: 3.42%-5.34%), 12.53% (95% CI: 10.74%-14.59%), 20.44% (95% CI: 17.37%-23.98%) and 30.82% (95% CI: 20.20%-45.21%), respectively. Male gender (HR = 1.771, p = 0.004), diabetes (HR = 1.923, p < .001), alcohol abuse (HR = 1.503, p = 0.025) and pancreaticoduodenectomy (HR = 2.901, p < 0.001) were independent risk factors for steatorrhea while CP in adolescents (HR = 0.433, p = 0.009) was a protective factor. In conclusion, male gender, adult, diabetes, alcohol abuse and pancreaticoduodenectomy lead to increased risk of steatorrhea in CP patients. PMID- 26877250 TI - Accelerated progression of Hodgkin's-like lymphomas in golli deficient SJL mice. AB - Spontaneously occurring lymphomas in SJL mice have many pathological features similar to Hodgkin's lymphoma in humans. The malignant growth of the tumor cells is dependent on the support of host FoxP3(+)CD4(+) regulatory T cells (Tregs). In this study, we report that the ablation of golli protein, a negative regulator of CRAC (calcium release activated calcium) channel, in SJL mice results in an accelerated progression of Hodgkin's-like lymphoma which is accompanied by a facilitated conversion of FoxP3(+) Treg cells. Our results suggest that golli protein might affect the progression of Hodgkin's-like lymphomas through regulating the induction of Treg cells. PMID- 26877252 TI - Stimulated photon emission and two-photon Raman scattering in a coupled-cavity QED system. AB - We study the scattering problem of photon and polariton in a one-dimensional coupled-cavity system. Analytical approximate analysis and numerical simulation show that a photon can stimulate the photon emission from a polariton through polariton-photon collisions. This observation opens the possibility of photon stimulated transition from insulating to radiative phase in a coupled-cavity QED system. Inversely, we also find that a polariton can be generated by a two-photon Raman scattering process. This paves the way towards single photon storage by the aid of atom-cavity interaction. PMID- 26877253 TI - Evaluation of the Impact of a Pharmacist-Led Telehealth Clinic on Diabetes Related Goals of Therapy in a Veteran Population. AB - OBJECTIVES: Telemedicine has been offered as a way to ensure that all patients, including those who live in rural areas, have access to the same health care. This study was performed to evaluate the benefit of a real-time, clinic-based video telehealth (Clinical Video Telehealth [CVT]) program and the impact of a pharmacist-led CVT clinic for chronic disease state management. The primary objective was to evaluate changes from baseline values, in veterans referred by primary care providers to this clinic. METHODS: This was a single-center, prospective, pre-post pilot study that also included a post-patient satisfaction survey. The study was conducted at the Tennessee Valley Healthcare System, which is composed of two medical centers and 12 community-based outpatient clinics (CBOCs) located away from the two main facilities. Fifteen clinical pharmacy specialists (CPSs)-seven at the two main facilities and eight at the CBOCs provide disease state management clinical pharmacy services. One of the seven CPSs at the main facilities works via telemedicine and provides services to the CBOCs where on-site clinical pharmacy services did not exist. The primary outcomes were changes from baseline in A1C, LDL level, systolic blood pressure, and diastolic blood pressure after 6 months of CVT services by the CPS. Secondary outcomes were the percentages of patients meeting American Diabetes Association treatment goals for hemoglobin A1c (A1C), low-density lipoprotein level, and blood pressure, both individually and in combination after attending a pharmacist led CVT program; the level of patient satisfaction with pharmacists' care and with CVT as a method of receiving chronic disease management, specifically for diabetes; and medication additions or changes made by the pharmacist. RESULTS: Twenty-six patients completed the 6-month evaluation. A significant decrease in A1C of 2% from baseline was observed (p=0.0002), and the percentage of patients meeting goal A1C significantly increased from 0% at baseline to 38% at 6 months (p=0.0007). Overall patient satisfaction scores were also high, with a median score 39.5 (interquartile range 36-40) of a maximum score of 40. CONCLUSION: Six months of CVT clinic attendance significantly improved A1C values and the overall percentage of patients meeting their goal A1C values in this veteran population. In addition, patient satisfaction scores also indicated a high level of satisfaction with the pharmacist-led CVT service. PMID- 26877251 TI - Strategies to target long-lived plasma cells for treating hemophilia A inhibitors. AB - Long-lived plasma cells (LLPCs) can persistently produce anti-factor VIII (FVIII) antibodies which disrupt therapeutic effect of FVIII in hemophilia A patients with inhibitors. The migration of plasma cells to BM where they become LLPCs is largely controlled by an interaction between the chemokine ligand CXCL12 and its receptor CXCR4. AMD3100 combined with G-CSF inhibit their interactions, thus facilitating the mobilization of CD34(+) cells and blocking the homing of LLPCs. These reagents were combined with anti-CD20 to reduce B-cells and the specific IL 2/IL-2mAb (JES6-1) complexes to induce Treg expansion for targeting anti-FVIII immune responses. Groups of mice primed with FVIII plasmid and protein respectively were treated with the combined regimen for six weeks, and a significant reduction of anti-FVIII inhibitor titers was observed, associated with the dramatic decrease of circulating and bone marrow CXCR4(+) plasma cells. The combination regimens are highly promising in modulating pre-existing anti FVIII antibodies in FVIII primed subjects. PMID- 26877254 TI - Mass spectrometric detection of 27-hydroxycholesterol in breast cancer exosomes. AB - Exosomes from cancer cells are rich sources of biomarkers and may contain elevated levels of lipids of diagnostic value. 27-Hydroxycholesterol (27-OHC) is associated with proliferation and metastasis in estrogen receptor positive (ER+) breast cancer. In this study, we investigated the levels of 27-OHC, and other sidechain-hydroxylated oxysterols in exosomes. To study both cytoplasmic and exosomal oxysterol samples of limited size, we have developed a capillary liquid chromatography-mass spectrometry platform that outperforms our previously published systems regarding chromatographic resolution, analysis time and sensitivity. In the analyzed samples, the quantified level of cytoplasmic 27-OHC using this platform fitted with mRNA levels of 27-OHC's corresponding enzyme, CYP27A1. We find clearly increased levels of 27-OHC in exosomes (i.e., enrichment) from an ER+ breast cancer cell line (MCF-7) compared to exosomes derived from an estrogen receptor (ER-) breast cancer cell line (MDA-MB-231) and other control exosomes (non-cancerous cell line (HEK293) and human pooled serum). The exosomal oxysterol profile did not reflect cytoplasmic oxysterol profiles in the cells of origin; cytoplasmic 27-OHC was low in ER+ MCF-7 cells while high in MDA-MB-231 cells. Other control cancer cells showed varied cytoplasmic oxysterol levels. Hence, exosome profiling in cancer cells might provide complementary information with the possibility of diagnostic value. PMID- 26877255 TI - Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome. AB - The conventional Delta5 and Delta4 steroidogenic pathways mediate androgen production in females. While multiple non-conventional pathways to dihydrotestosterone (DHT) have recently been postulated in humans, the functional significance of these pathways remains to be elucidated. The aim of this study was to clarify the origin of androgens in healthy women and in patients with polycystic ovary syndrome (PCOS), a multifactorial disorder characterized by androgen overproduction. We measured 13 steroids in blood samples of 31 eumenorrheic females and 28 PCOS patients using liquid chromatography-tandem mass spectrometry and chemiluminescent enzyme immunoassay. We found that 17-hydroxy (17-OH) progesterone (17-OHP), androstenedione (Delta4A), testosterone, androstanedione, androsterone, and androstanediol levels were higher in the patient group than in the eumenorrheic group, while levels of other steroids were comparable between the two groups. In the eumenorrheic group, DHT levels were correlated with testosterone, androstanedione, and androstanediol. Quantitative correlations were also observed among 17-OH allopregnanolone, androsterone, androstanediol, and DHT, and among Delta4A, androstanedione, androsterone, and androstanediol. In the patient group, DHT levels were correlated with testosterone levels, but not with androstanedione or androstanediol levels. Delta4A and testosterone paralleled 17-OHP. Androstanedione, androsterone, androstanediol, and 17-OH allopregnanolone were quantitatively correlated. In both groups, multivariable linear regression analyses suggested relationships between androsterone and androstanedione, as well as between androsterone and 17 OH allopregnanolone. These results indicate that multiple androgen biosynthesis pathways are operating in eumenorrheic females and PCOS patients. In PCOS patients, excessive androgens are produced primarily via the conventional pathways, while two alternative pathways; i.e., an androstanedione-mediated pathway and a so-called backdoor pathway, likely serve as sources of a weak androgen and potential precursors of DHT. PMID- 26877257 TI - Theoretical study of phase stability and elastic properties of T 0.75Y0.75B14 (T = Sc, Ti, V, Y, Zr, Nb, Si). AB - In this study the phase stability, elastic properties, and plastic behaviour of icosahedral transition metal borides T 0.75Y0.75B14 (T = Sc, Ti, V, Y, Zr, Nb, Si) have been investigated using density functional theory. Phase stability critically depends on the charge transferred by T and Y to the B icosahedra. For the metal sublattice occupancy investigated here, the minimum energy of formation is identified at an effective B icosahedra charge of - 1.8 +/- 0.1. This charge corridor encompasses the highest phase stability among all the reported icosahedral transition metal boride systems so far. This data provides guidance for future experimental efforts: from a wear-resistance point of view, Sc0.75Y0.75B14, Ti0.75Y0.75B14, and Zr0.75Y0.75B14 exhibit a rather unique and attractive combination of large Young's modulus values ranging from 488 to 514 GPa with the highest phase stability for icosahedral transition metals borides reported so far. PMID- 26877258 TI - Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors. AB - Carboxy-terminal telopeptide of type I collagen (ICTP) is generated through matrix metalloproteinase (MMP)-dependent type I collagen digestion, and has been widely utilized as a biomarker for bone turnover. The fact that atherosclerotic lesions are rich in both type I collagen and MMP-producing macrophages led to the hypothesis that serum ICTP concentrations may serve as a non-invasive clinical biomarker for atherosclerosis. Therefore, the association of serum ICTP concentrations with the maximum intima-media thickness (IMT) of carotid arteries, a surrogate index of systemic atherosclerosis, or brachial-ankle pulse wave velocity (baPWV) in patients with atherosclerotic risk factors was evaluated. A total of 52 male and 65 female (mean age: 62.8 yrs) patients without renal failure, malignancies or bone diseases known to affect serum ICTP concentrations were recruited. Patients with max IMTs >=1.1 mm showed significantly higher serum ICTP concentrations compared with patients with max IMTs <1.1 mm (3.33 +/- 0.97 vs 2.82 +/- 0.65 ng/mL, p<0.05). Serum ICTP concentration was also positively correlated with max IMT (p<0.001) or baPWV values (p<0.05). Multivariate analyses also revealed that serum ICTP concentrations were correlated with max IMT (p<0.001; 95% CI 0.200 to 0.454). These results suggest that serum ICTP concentrations can be used as a non-invasive biomarker for systemic atherosclerosis. PMID- 26877259 TI - Identification and Analysis of Electrochemical Instrumentation Limitations through the Study of Platinum Surface Oxide Formation and Reduction. AB - Anodic polarization of Pt electrodes in aqueous H2SO4 leads to the formation of a surface oxide (PtO). Herein, the surface oxide growth is accomplished using three different approaches: (i) chronoamperometry (CA); (ii) chronocoulometry (CC); and (iii) a combination of cyclic voltammetry (CV) and CA. The PtO reduction is accomplished potentiodynamically using voltammetry. The oxide growth takes place at defined polarization potentials (E(p)), polarization times (t(p)), and temperatures (T). The oxide charge density (q(ox)) is determined for both the formation (q(ox,form)) and reduction (q(ox,red)) processes. The oxide reduction CV profiles are integrated to determine the charge density values for oxide reduction (q(ox,red,CV)) which are compared with the q(ox,form,CA) and q(ox,form,CC) values. The values of q(ox,form,CC) are greater than those of q(ox,form,CA), but both potentiotatic methods (CA and CC) produce q(ox,form) values that are consistently lower than those of q(ox,red,CV). In the case of oxide formation with combined CV and CA, the values of q(ox,form,CV+CA) are found to be lower than the values of q(ox,red,CV), although the difference is small. Electrochemical quartz crystal nanobalance (EQCN) is used to monitor the mass variation at the electrode surface during the oxide formation and reduction process at E(p) = 1.20 V with various t(p) values. Equal mass changes during oxide formation and reduction are detected by the EQCN. The nature of the differences in q(ox,form) and q(ox,red) encountered with the different experimental methods are discussed in terms of instrumental limitations. PMID- 26877256 TI - Prenatal inflammation-induced NF-kappaB dyshomeostasis contributes to renin angiotensin system over-activity resulting in prenatally programmed hypertension in offspring. AB - Studies involving the use of prenatally programmed hypertension have been shown to potentially contribute to prevention of essential hypertension (EH). Our previous research has demonstrated that prenatal inflammatory stimulation leads to offspring's aortic dysfunction and hypertension in pregnant Sprague-Dawley rats challenged with lipopolysaccharide (LPS). The present study found that prenatal LPS exposure led to NF-kappaB dyshomeostasis from fetus to adult, which was characterized by PI3K-Akt activation mediated degradation of IkappaBalpha protein and impaired NF-kappaB self-negative feedback loop mediated less newly synthesis of IkappaBalpha mRNA in thoracic aortas (gestational day 20, postnatal week 7 and 16). Prenatal or postnatal exposure of the IkappaBalpha degradation inhibitor, pyrollidine dithiocarbamate, effectively blocked NF-kappaB activation, endothelium dysfunction, and renin-angiotensin system (RAS) over-activity in thoracic aortas, resulting in reduced blood pressure in offspring that received prenatal exposure to LPS. Surprisingly, NF-kappaB dyshomeostasis and RAS over activity were only found in thoracic aortas but not in superior mesenteric arteries. Collectively, our data demonstrate that the early life NF-kappaB dyshomeostasis induced by prenatal inflammatory exposure plays an essential role in the development of EH through triggering RAS over-activity. We conclude that early life NF-kappaB dyshomeostasis is a key predictor of EH, and thus, NF-kappaB inhibition represents an effective interventional strategy for EH prevention. PMID- 26877260 TI - Dairy Product, Calcium Intake and Lung Cancer Risk: A Systematic Review with Meta Analysis. AB - The effects of dairy products on human health have been studied for years. However, the relationship between dairy products as well as calcium intake and the risk of lung cancer is still inconclusive. A total of 32 studies regarding this association were identified from the PubMed and Web of Science databases through April 1, 2015, including 12 cohort studies and 20 case-control studies. After pooling the results of individual studies, the summary RRs (relative risks) of lung cancer for the highest versus lowest intake were 1.05 (95%CI: 0.84-1.31) and 1.08 (95%CI: 0.80-1.46) for total dairy products and milk, respectively. The results on the consumption of cheese, yogurt and low-fat milk were also negative, and the RRs for total and dietary calcium intakes were 0.99 (95%CI: 0.70-1.38) and 0.85 (95%CI: 0.63-1.13), respectively. After stratifying by potential confounders, the results remained consistent in most subgroup analyses. Our study indicates that intake of dairy products or calcium was not statistically associated with the risk of lung cancer. This negative finding provides a conclusive answer to the disease association issue based on current evidence, and suggests that further efforts should be made to find other nutritional risk factors for lung cancer. PMID- 26877261 TI - Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma. AB - Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. PMID- 26877264 TI - A morphology, porosity and surface conductive layer optimized MnCo2O4 microsphere for compatible superior Li(+) ion/air rechargeable battery electrode materials. AB - Uniform surface conductive layers with porous morphology-conserved MnCo2O4 microspheres are successfully synthesized, and their electrochemical performances are thoroughly investigated. It is found that the microwave-assisted hydrothermally grown MnCo2O4 using citric acid as the carbon source shows a maximum Li(+) ion lithiation/delithiation capacity of 501 mA h g(-1) at 500 mA g( 1) with stable capacity retention. Besides, the given microsphere compounds are effectively activated as air cathode catalysts in Li-O2 batteries with reduced charge overpotentials and improved cycling performance. We believe that such an affordable enhanced performance results from the appropriate quasi-hollow nature of MnCo2O4 microspheres, which can effectively mitigate the large volume change of electrodes during Li(+) migration and/or enhance the surface transport of the LiOx species in Li-air batteries. Thus, the rationally designed porous media for the improved Li(+) electrochemical reaction highlight the importance of the 3D macropores, the high specific area and uniformly overcoated conductive layer for the promising Li(+) redox reaction platforms. PMID- 26877262 TI - Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma. AB - Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID- 26877265 TI - Foam drainage in the presence of solid particles. AB - We conducted forced drainage experiments to study the liquid flow within the foams stabilized by a cationic surfactant (CTAB) in the presence of partially hydrophobic silica particles. The results show that the presence of solid particles, even when present in small amounts (0.0932 g L(-1) foam), can significantly decrease the foam permeability. The scaling behaviour (power law) between the drainage velocity and the imposed flow rate indicates that the presence of solid particles in the foams triggers a transition of the foam drainage regime from a node-dominated regime to a Plateau border-dominated regime. We applied two foam drainage equations for aqueous foams to simulate the experimental data and interpret the transition. The simulation results show that the presence of solid particles in the foams increases the rigidity of the interfaces and the viscous losses in the channels (the Plateau borders) of the foams, and decreases the foam permeability. We also generalize the theory for the effects of unattached hydrophilic particles on foam drainage by considering the effects of hydrophobicity and concentration of solid particles on the confinement of foam networks. This study explores liquid drainage in three-phase foams and is relevant to the field of hydrophobic particle separation by froth flotation, in which the wash water is commonly applied to the froth layer to improve the product grade. PMID- 26877263 TI - Activity induces traveling waves, vortices and spatiotemporal chaos in a model actomyosin layer. AB - Inspired by the actomyosin cortex in biological cells, we investigate the spatiotemporal dynamics of a model describing a contractile active polar fluid sandwiched between two external media. The external media impose frictional forces at the interface with the active fluid. The fluid is driven by a spatially homogeneous activity measuring the strength of the active stress that is generated by processes consuming a chemical fuel. We observe that as the activity is increased over two orders of magnitude the active polar fluid first shows spontaneous flow transition followed by transition to oscillatory dynamics with traveling waves and traveling vortices in the flow field. In the flow-tumbling regime, the active polar fluid also shows transition to spatiotemporal chaos at sufficiently large activities. These results demonstrate that level of activity alone can be used to tune the operating point of actomyosin layers with qualitatively different spatiotemporal dynamics. PMID- 26877266 TI - Correction: Miscibility studies of two twist-bend nematic liquid crystal dimers with different average molecular curvatures. A comparison between experimental data and predictions of a Landau mean-field theory for the NTB-N phase transition. AB - Correction for 'Miscibility studies of two twist-bend nematic liquid crystal dimers with different average molecular curvatures. A comparison between experimental data and predictions of a Landau mean-field theory for the NTB-N phase transition' by D. O. Lopez et al., Phys. Chem. Chem. Phys., 2016, 18, 4394 4404. PMID- 26877267 TI - Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization. AB - The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals. PMID- 26877537 TI - Involvement of Staphylococcus aureus and Moraxella catarrhalis in Japanese cedar pollinosis. AB - BACKGROUND AND OBJECTIVE: From mid February to the end of March, each year ~30% of Japanese have Japanese cedar pollinosis. Moreover, 10-50% of patients with this pollinosis exhibit nasal manifestations in the preseason. These patients have a predominance of neutrophils but not eosinophils in nasal swabs and high carriage of Staphylococcus aureus. We hypothesized that S. aureus or other bacteria and associated neutrophilia were involved in preseasonal symptoms. METHODS: Cytology and bacterial colony growth were assessed in nasal swabs in the groups of asymptomatic patients in the preseason (PreAsP) (n = 53) and symptomatic patients in the preseason (PreSyP) (n = 60), and in group of symptomatic patients in season (InSyP) (n = 72). RESULTS: In the preseason, high neutrophilia was present in only 20% of the PreAsP group but in 47% of the PreSyP group (p < 0.01). Nasal carriage of S. aureus in the PreAsP and PreSyP groups were 79%, 75%, respectively, whereas, for Moraxella catarrhalis, these were 9% versus 25% (PreAsP versus PreSyP group; p < 0.05). In patients with positive results for S. aureus and M. catarrhalis, the degrees of neutrophilia (-, +/-, +, 2+, 3+) in the PreSyP group were larger than in the PreAsP groups (p < 0.01). In the PreSyP group, the magnitude of neutrophilia was greater (p < 0.05) in subgroups with more colonies of S. aureus than in subgroups with fewer colonies. CONCLUSION: Nasal symptoms in the preseason are associated with neutrophilia and nasal colonization with S. aureus and M. catarrhalis. Patients with symptoms in the preseason had improved symptom scores when given prophylactic treatment early in season but had more-severe symptom scores late in season than asymptomatic patients in the preseason. Neutrophil-associated tissue damage related to bacterial colonization may underlie these associations. PMID- 26877538 TI - High pressure effects on U L3 x-ray absorption in partial fluorescence yield mode and single crystal x-ray diffraction in the heavy fermion compound UCd11. AB - We report a study of high pressure x-ray absorption (XAS) performed in the partial fluorescence yield mode (PFY) at the U L3 edge (0-28.2 GPa) and single crystal x-ray diffraction (SXD) (0-20 GPa) on the UCd11 heavy fermion compound at room temperature. Under compression, the PFY-XAS results show that the white line is shifted by +4.1(3) eV at the highest applied pressure of 28.2 GPa indicating delocalization of the 5f electrons. The increase in full width at half maxima and decrease in relative amplitude of the white line with respect to the edge jump point towards 6d band broadening under high pressure. A bulk modulus of K0 = 62(1) GPa and its pressure derivative, K0 = 4.9(2) was determined from high pressure SXD results. Both the PFY-XAS and diffraction results do not show any sign of a structural phase transition in the applied pressure range. PMID- 26877539 TI - Squamous cell carcinoma antigen as a diagnostic marker of nasal inverted papilloma. AB - BACKGROUND: Serum squamous cell carcinoma antigen (SCCA) levels are elevated in sinonasal inverted papilloma (IP). However, the relationship between tumor volume and SCCA level, and the influence of skin or pulmonary diseases in which the SCCA level is high, have not been established. OBJECTIVE: To clarify whether the level of serum SCCA can be used as a diagnostic marker of IP. METHODS: Serum SCCA level was measured in 30 patients with IP (IP group) and 57 with inflammatory disease (inflammatory group). RESULTS: Overall, 83.3% in the IP group showed elevated serum SCCA levels regardless of whether they were new patients or patients with recurrent IP, and SCCA levels rapidly decreased after surgery. Only 5.3% had elevated SCCA levels in the inflammatory group. Before surgery, the IP group had a median preoperative SCCA level of 2.4 ng/mL, whereas the median preoperative SCCA level was 0.9 ng/mL in the inflammatory group. Pre- and postoperative SCCA levels were significantly different in the IP group. With regard to the IP diagnosis in the IP and inflammatory groups based on the SCCA level (<=1.5 ng/mL), sensitivity and specificity were 83.3% and 94.7%, respectively. There was no significant correlation between SCCA elevation and respiratory function, and skin disease in the two groups, except for smoking in the IP group. Preoperative SCCA levels were significantly higher in smokers than in never-smokers in the IP group. Tumor volume was significantly correlated with SCCA level in IP. Multivariable logistic analysis showed that tumor volume was a predictor of preoperative SCCA elevation (p = 0.036; 95% confidence interval, 1.027-2.176). CONCLUSION: Serum SCCA level is a reliable diagnostic marker to distinguish new and recurrent IP from inflammatory disease. Because smokers tended to have higher SCCA levels in IP, a different cutoff level might be needed. Although respiratory dysfunction and skin disease were not related to SCCA level, they should be taken into consideration when evaluating SCCA level. PMID- 26877540 TI - Managing arrhythmias: diagnosis and modern treatment. PMID- 26877541 TI - CardioPulse: Gerhard Hindricks MD. PMID- 26877542 TI - Male bumblebees, Bombus terrestris, perform equally well as workers in a serial colour-learning task. AB - The learning capacities of males and females may differ with sex-specific behavioural requirements. Bumblebees provide a useful model system to explore how different lifestyles are reflected in learning abilities, because their (female but sterile) workers and males engage in fundamentally different behaviour routines. Bumblebee males, like workers, embark on active flower foraging but in contrast to workers they have to trade off their feeding with mate search, potentially affecting their abilities to learn and utilize floral cues efficiently during foraging. We used a serial colour-learning task with freely flying males and workers to compare their ability to flexibly learn visual floral cues with reward in a foraging scenario that changed over time. Male bumblebees did not differ from workers in both their learning speed and their ability to overcome previously acquired associations, when these ceased to predict reward. In all foraging tasks we found a significant improvement in choice accuracy in both sexes over the course of the training. In both sexes, the characteristics of the foraging performance depended largely on the colour difference of the two presented feeder types. Large colour distances entailed fast and reliable learning of the rewarding feeders whereas choice accuracy on highly similar colours improved significantly more slowly. Conversely, switching from a learned feeder type to a novel one was fastest for similar feeder colours and slow for highly different ones. Overall, we show that behavioural sex dimorphism in bumblebees did not affect their learning abilities beyond the mating context. We discuss the possible drivers and limitations shaping the foraging abilities of males and workers and implications for pollination ecology. We also suggest stingless male bumblebees as an advantageous alternative model system for the study of pollinator cognition. PMID- 26877543 TI - Future flavour physics experiments. AB - The current status of flavour physics and the prospects for present and future experiments will be reviewed. Measurements in B-physics, in which sensitive probes of new physics are the CKM angle gamma, the Bs mixing phase phis, and the branching ratios of the rare decays B(s)0->MU+MU- , will be highlighted. Topics in charm and kaon physics, in which the measurements of ACP and the branching ratios of the rare decays K->pinunu- are key measurements, will be discussed. Finally the complementarity of the future heavy flavour experiments, the LHCb upgrade and Belle-II, will be summarised. PMID- 26877544 TI - Maximizing dietary information retrievable from carcasses of Great Cormorants Phalacrocorax carbo using a combined morphological and molecular analytical approach. AB - Avian carcasses can provide important information on the trophic ecology of birds. Usually, the number of carcasses available for examination is limited and therefore it is important to gain as much dietary information per specimen as possible. In piscivorous birds and raptors, the stomach has been the primary source of dietary information, whereas the gut (intestine) has so far been neglected as it usually contains only a few morphologically identifiable hard parts of prey. Molecular approaches have the potential to retrieve dietary information from the gut, although this has not yet been verified. As well as identifying the prey, it is important to estimate any secondary predation to avoid food web errors in dietary analyses. The assignment of accidentally consumed prey is notoriously difficult regardless of the prey identification approach used. In the present study, morphological and molecular analyses were, for the first time, combined to maximize the dietary information retrievable from the complete digestive tract of Great Cormorants Phalacrocorax carbo sinensis. Moreover, a novel approach based on predator-prey size ratios was applied to these piscivorous birds to minimize the number of samples that might contain secondarily predated prey. The stomach contents of the examined birds were found to provide the most dietary information when morphological and molecular analyses were used in combination. However, compared with the morphological approach, the molecular analysis increased the number of fish species detected by 39%. The molecular approach also permitted the identification of fish DNA in the Cormorant guts. Predator-prey size ratios derived from morphological analysis of fish hard parts can reduce the incidence of potential confounding influence of secondarily predated prey by 80%. Our findings demonstrate that a combination of morphological and molecular approaches maximizes the trophic information retrievable from bird carcasses. PMID- 26877545 TI - Integrating spatially explicit indices of abundance and habitat quality: an applied example for greater sage-grouse management. AB - Predictive species distributional models are a cornerstone of wildlife conservation planning. Constructing such models requires robust underpinning science that integrates formerly disparate data types to achieve effective species management.Greater sage-grouse Centrocercus urophasianus, hereafter 'sage grouse' populations are declining throughout sagebrush-steppe ecosystems in North America, particularly within the Great Basin, which heightens the need for novel management tools that maximize the use of available information.Herein, we improve upon existing species distribution models by combining information about sage-grouse habitat quality, distribution and abundance from multiple data sources. To measure habitat, we created spatially explicit maps depicting habitat selection indices (HSI) informed by >35 500 independent telemetry locations from >1600 sage-grouse collected over 15 years across much of the Great Basin. These indices were derived from models that accounted for selection at different spatial scales and seasons. A region-wide HSI was calculated using the HSI surfaces modelled for 12 independent subregions and then demarcated into distinct habitat quality classes.We also employed a novel index to describe landscape patterns of sage-grouse abundance and space use (AUI). The AUI is a probabilistic composite of the following: (i) breeding density patterns based on the spatial configuration of breeding leks and associated trends in male attendance; and (ii) year-round patterns of space use indexed by the decreasing probability of use with increasing distance to leks. The continuous AUI surface was then reclassified into two classes representing high and low/no use and abundance. Synthesis and applications. Using the example of sage-grouse, we demonstrate how the joint application of indices of habitat selection, abundance and space use derived from multiple data sources yields a composite map that can guide effective allocation of management intensity across multiple spatial scales. As applied to sage-grouse, the composite map identifies spatially explicit management categories within sagebrush steppe that are most critical to sustaining sage-grouse populations as well as those areas where changes in land use would likely have minimal impact. Importantly, collaborative efforts among stakeholders guide which intersections of habitat selection indices and abundance and space use classes are used to define management categories. Because sage grouse are an umbrella species, our joint-index modelling approach can help target effective conservation for other sagebrush obligate species and can be readily applied to species in other ecosystems with similar life histories, such as central-placed breeding. PMID- 26877546 TI - FORUM: Indirect leakage leads to a failure of avoided loss biodiversity offsetting. AB - Biodiversity offsetting has quickly gained political support all around the world. Avoided loss (averted risk) offsetting means compensation for ecological damage via averted loss of anticipated impacts through the removal of threatening processes in compensation areas.Leakage means the phenomenon of environmentally damaging activity relocating elsewhere after being stopped locally by avoided loss offsetting. Indirect leakage means that locally avoided losses displace to other administrative areas or spread around diffusely via market effects. Synthesis and applications. Indirect leakage can lead to high net biodiversity loss. It is difficult to measure or prevent, raising doubts about the value of avoided loss offsetting. Market demand for commodities is on the rise, following increasing human population size and per capita consumption, implying that indirect leakage will be a rule rather than an exception. Leakage should be accounted for when determining offset multipliers (ratios) even if multipliers become extremely high. PMID- 26877547 TI - A psychological predictor of elders' driving performance: social-comparisons on the road. AB - Older individuals often believe they can drive better than their contemporaries. This belief is an example of downward social-comparisons; they can be self enhancing tools that lead to beneficial outcomes. As predicted, we found that drivers who engaged in downward social-comparisons were significantly less likely to have adverse driving events over time, after controlling for relevant factors (p = .02). This effect was particularly strong among women, who tend to experience more negative driving stereotypes (p = .01). The study was based on 897 interviews of 117 elder drivers, aged 70-89 years, over 2 years. Our findings suggest that interventions to reduce adverse driving events among elders could benefit from including a psychological component. PMID- 26877548 TI - Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study. AB - Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID- 26877549 TI - Determinants of flammability in savanna grass species. AB - Tropical grasses fuel the majority of fires on Earth. In fire-prone landscapes, enhanced flammability may be adaptive for grasses via the maintenance of an open canopy and an increase in spatiotemporal opportunities for recruitment and regeneration. In addition, by burning intensely but briefly, high flammability may protect resprouting buds from lethal temperatures. Despite these potential benefits of high flammability to fire-prone grasses, variation in flammability among grass species, and how trait differences underpin this variation, remains unknown.By burning leaves and plant parts, we experimentally determined how five plant traits (biomass quantity, biomass density, biomass moisture content, leaf surface-area-to-volume ratio and leaf effective heat of combustion) combined to determine the three components of flammability (ignitability, sustainability and combustibility) at the leaf and plant scales in 25 grass species of fire-prone South African grasslands at a time of peak fire occurrence. The influence of evolutionary history on flammability was assessed based on a phylogeny built here for the study species.Grass species differed significantly in all components of flammability. Accounting for evolutionary history helped to explain patterns in leaf-scale combustibility and sustainability. The five measured plant traits predicted components of flammability, particularly leaf ignitability and plant combustibility in which 70% and 58% of variation, respectively, could be explained by a combination of the traits. Total above-ground biomass was a key driver of combustibility and sustainability with high biomass species burning more intensely and for longer, and producing the highest predicted fire spread rates. Moisture content was the main influence on ignitability, where species with higher moisture contents took longer to ignite and once alight burnt at a slower rate. Biomass density, leaf surface-area-to-volume ratio and leaf effective heat of combustion were weaker predictors of flammability components. Synthesis. We demonstrate that grass flammability is predicted from easily measurable plant functional traits and is influenced by evolutionary history with some components showing phylogenetic signal. Grasses are not homogenous fuels to fire. Rather, species differ in functional traits that in turn demonstrably influence flammability. This diversity is consistent with the idea that flammability may be an adaptive trait for grasses of fire-prone ecosystems. PMID- 26877550 TI - Synthesis and Photophysical and Electroluminescent Properties of Poly(1,4 phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene)s with Various Dissymmetric Substitution of Alkoxy Side Chains. AB - The synthesis and characterization of a set of conjugated polymers, poly(1,4 phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene)s (PPE-PPVs), with a dissymmetrical configuration (partial or total) of alkoxy side chains is reported. Five new polymers bearing octyloxy and/or octadecyloxy side chains at the phenylene-ethynylene and phenylene-vinylene segments, respectively, were obtained. Two symmetrical substituted polymers were used for comparison. Polymers with weight-average molecular weight, Mw, up to 430 000 g/mol and degree of polymerization between 17 and 322 were obtained by a Horner-Wadsworth-Emmons olefination polycondensation reaction of the respective luminophoric dialdehydes and bisphosphonates. As expected, identical conjugated backbones in all polymers results in very similar photophysical response in dilute solution, with high fluorescence quantum yields between 50% and 80%. In contrast, the thin film properties are dependent on the combinatorial effects of side chain configuration, molecular weight, and film thickness parameters, which are the basis of the resulting comparison and discussion. PMID- 26877551 TI - Metrological challenges for measurements of key climatological observables, Part 4: Atmospheric relative humidity. AB - Water in its three ambient phases plays the central thermodynamic role in the terrestrial climate system. Clouds control Earth's radiation balance, atmospheric water vapour is the strongest "greenhouse" gas, and non-equilibrium relative humidity at the air-sea interface drives evaporation and latent heat export from the ocean. In this paper, we examine the climatologically relevant atmospheric relative humidity, noting fundamental deficiencies in the definition of this key observable. The metrological history of this quantity is reviewed, problems with its current definition and measurement practice are analysed, and options for future improvements are discussed in conjunction with the recent seawater standard TEOS-10. It is concluded that the International Bureau of Weights and Measures, (BIPM), in cooperation with the International Association for the Properties of Water and Steam, IAPWS, along with other international organisations and institutions, can make significant contributions by developing and recommending state-of-the-art solutions for this long standing metrological problem, such as are suggested here. PMID- 26877552 TI - Determination of the fire hazards of mine materials using a radiant panel. AB - The objective of this study was to develop a laboratory-scale method to rank the ignition and fire hazards of commonly used underground mine materials and to eliminate the need for the expensive large-scale tests that are currently being used. A radiant-panel apparatus was used to determine the materials' relevant thermal characteristics: time to ignition, critical heat flux for ignition, heat of gasification, and mass-loss rate. Three thermal parameters, TRP, TP1 and TP4, were derived from the data, then developed and subsequently used to rank the combined ignition and fire hazards of the combustible materials from low hazard to high hazard. The results compared favorably with the thermal and ignition hazards of similar materials reported in the literature and support this approach as a simpler one for quantifying these combustible hazards. PMID- 26877553 TI - A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data. AB - Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts. PMID- 26877554 TI - A dose-schedule finding design for phase I-II clinical trials. AB - Dose-finding methods aiming at identifying an optimal dose of a treatment with a given schedule may be at a risk of misidentifying the best treatment for patients. In this article we propose a phase I/II clinical trial design to find the optimal dose-schedule combination. We define schedule as the method and timing of administration of a given total dose in a treatment cycle. We propose a Bayesian dynamic model for the joint effects of dose and schedule. The proposed model allows us to borrow strength across dose-schedule combinations without making overly restrictive assumptions on the ordering pattern of the schedule effects. We develop a dose-schedule-finding algorithm to sequentially allocate patients to a desirable dose-schedule combination, and select an optimal combination at the end of the trial. We apply the proposed design to a phase I/II clinical trial of a gamma-secretase inhibitor in patients with refractory metastatic or locally advanced solid tumours, and examine the operating characteristics of the design through simulations. PMID- 26877555 TI - STABILITY OF A CYLINDRICAL SOLUTE-SOLVENT INTERFACE: EFFECT OF GEOMETRY, ELECTROSTATICS, AND HYDRODYNAMICS. AB - The solute-solvent interface that separates biological molecules from their surrounding aqueous solvent characterizes the conformation and dynamics of such molecules. In this work, we construct a solvent fluid dielectric boundary model for the solvation of charged molecules and apply it to study the stability of a model cylindrical solute-solvent interface. The motion of the solute-solvent interface is defined to be the same as that of solvent fluid at the interface. The solvent fluid is assumed to be incompressible and is described by the Stokes equation. The solute is modeled simply by the ideal-gas law. All the viscous force, hydrostatic pressure, solute-solvent van der Waals interaction, surface tension, and electrostatic force are balanced at the solute-solvent interface. We model the electrostatics by Poisson's equation in which the solute-solvent interface is treated as a dielectric boundary that separates the low-dielectric solute from the high-dielectric solvent. For a cylindrical geometry, we find multiple cylindrically shaped equilibrium interfaces that describe polymodal (e.g., dry and wet) states of hydration of an underlying molecular system. These steady-state solutions exhibit bifurcation behavior with respect to the charge density. For their linearized systems, we use the projection method to solve the fluid equation and find the dispersion relation. Our asymptotic analysis shows that, for large wavenumbers, the decay rate is proportional to wavenumber with the proportionality half of the ratio of surface tension to solvent viscosity, indicating that the solvent viscosity does affect the stability of a solute solvent interface. Consequences of our analysis in the context of biomolecular interactions are discussed. PMID- 26877556 TI - DIFFUSED SOLUTE-SOLVENT INTERFACE WITH POISSON-BOLTZMANN ELECTROSTATICS: FREE ENERGY VARIATION AND SHARP-INTERFACE LIMIT. AB - A phase-field free-energy functional for the solvation of charged molecules (e.g., proteins) in aqueous solvent (i.e., water or salted water) is constructed. The functional consists of the solute volumetric and solute-solvent interfacial energies, the solute-solvent van der Waals interaction energy, and the continuum electrostatic free energy described by the Poisson-Boltzmann theory. All these are expressed in terms of phase fields that, for low free-energy conformations, are close to one value in the solute phase and another in the solvent phase. A key property of the model is that the phase-field interpolation of dielectric coefficient has the vanishing derivative at both solute and solvent phases. The first variation of such an effective free-energy functional is derived. Matched asymptotic analysis is carried out for the resulting relaxation dynamics of the diffused solute-solvent interface. It is shown that the sharp-interface limit is exactly the variational implicit-solvent model that has successfully captured capillary evaporation in hydrophobic confinement and corresponding multiple equilibrium states of underlying biomolecular systems as found in experiment and molecular dynamics simulations. Our phase-field approach and analysis can be used to possibly couple the description of interfacial fluctuations for efficient numerical computations of biomolecular interactions. PMID- 26877557 TI - 'Other' Posts in 'Other' Places: Poland through a Postcolonial Lens? AB - Postcolonial theory has tended to focus on those spaces where European colonialism has had a territorial and political history. This is unsurprising, as much of the world is in this sense 'postcolonial'. But not all of it. This article focuses on Poland, often theorised as peripheral to 'old Europe', and explores the application of postcolonial analyses to this 'other' place. The article draws upon reflections arising from a study of responses to ethnic diversity in Warsaw, Poland. In doing so we conclude that postcolonialism does indeed offer some important insights into understanding Polish attitudes to other nationalities, and yet more work also needs to be done to make the theoretical bridge. In the case of Poland we propose the 'triple relation' be the starting point for such work. PMID- 26877558 TI - Governing through Prevent? Regulation and Contested Practice in State-Muslim Engagement. AB - In this article, we consider the implications of the 'Prevent' strand of the government's counter-terrorism strategy for the UK state's engagement with Muslims. We argue that the logics of Prevent have been highly problematic for state-Muslim engagement. Nevertheless, we suggest that the characterisation of state approaches to engaging Muslims as a form of discipline is incomplete without an analysis of: first, differences in practices, habits and perspectives across governance domains; second, variations in approach and implementation between levels of governance; and third, the agency of Muslims who engage with the state. Through this approach we show how attention to the situated practices of governance reveals the contested nature of governing through Prevent. PMID- 26877559 TI - Detection and attribution of urbanization effect on flood extremes using nonstationary flood-frequency models. AB - Urbanization is found to have an impact on high flows in a urbanized catchmentThe use of point processes is advocated for trend detection and attributionThe use of process-related covariates gives a better representation of change. PMID- 26877560 TI - Designing a sampling scheme to reveal correlations between weeds and soil properties at multiple spatial scales. AB - Weeds tend to aggregate in patches within fields, and there is evidence that this is partly owing to variation in soil properties. Because the processes driving soil heterogeneity operate at various scales, the strength of the relations between soil properties and weed density would also be expected to be scale dependent. Quantifying these effects of scale on weed patch dynamics is essential to guide the design of discrete sampling protocols for mapping weed distribution. We developed a general method that uses novel within-field nested sampling and residual maximum-likelihood (reml) estimation to explore scale-dependent relations between weeds and soil properties. We validated the method using a case study of Alopecurus myosuroides in winter wheat. Using reml, we partitioned the variance and covariance into scale-specific components and estimated the correlations between the weed counts and soil properties at each scale. We used variograms to quantify the spatial structure in the data and to map variables by kriging. Our methodology successfully captured the effect of scale on a number of edaphic drivers of weed patchiness. The overall Pearson correlations between A. myosuroides and soil organic matter and clay content were weak and masked the stronger correlations at >50 m. Knowing how the variance was partitioned across the spatial scales, we optimised the sampling design to focus sampling effort at those scales that contributed most to the total variance. The methods have the potential to guide patch spraying of weeds by identifying areas of the field that are vulnerable to weed establishment. PMID- 26877561 TI - Selective and Potent Proteomimetic Inhibitors of Intracellular Protein-Protein Interactions. AB - Inhibition of protein-protein interactions (PPIs) represents a major challenge in chemical biology and drug discovery. alpha-Helix mediated PPIs may be amenable to modulation using generic chemotypes, termed "proteomimetics", which can be assembled in a modular manner to reproduce the vectoral presentation of key side chains found on a helical motif from one partner within the PPI. In this work, it is demonstrated that by using a library of N-alkylated aromatic oligoamide helix mimetics, potent helix mimetics which reproduce their biophysical binding selectivity in a cellular context can be identified. PMID- 26877562 TI - Propensity Score-Based Methods versus MTE-Based Methods in Causal Inference: Identification, Estimation, and Application. AB - Since the seminal introduction of the propensity score by Rosenbaum and Rubin, propensity-score-based (PS-based) methods have been widely used for drawing causal inferences in the behavioral and social sciences. However, the propensity score approach depends on the ignorability assumption: there are no unobserved confounders once observed covariates are taken into account. For situations where this assumption may be violated, Heckman and his associates have recently developed a novel approach based on marginal treatment effects (MTE). In this paper, we (1) explicate consequences for PS-based methods when aspects of the ignorability assumption are violated; (2) compare PS-based methods and MTE-based methods by making a close examination of their identification assumptions and estimation performances; (3) apply these two approaches in estimating the economic return to college using data from NLSY 1979 and discuss their discrepancies in results. When there is a sorting gain but no systematic baseline difference between treated and untreated units given observed covariates, PS based methods can identify the treatment effect of the treated (TT). The MTE approach performs best when there is a valid and strong instrumental variable (IV). In addition, this paper introduces the "smoothing-difference PS-based method," which enables us to uncover heterogeneity across people of different propensity scores in both counterfactual outcomes and treatment effects. PMID- 26877564 TI - Terricolous Lichens in the Glacier Forefield of the Morteratsch Glacier (Eastern Alps, Graubunden, Switzerland). AB - Three sampling sites were established at increasing distance from the Morteratsch glacier to investigate lichen communities on soil in the glacier forefield. The survey yielded 13 lichen species and one lichenicolous fungus. Peltigera extenuata (Nyl. ex Vain.) Lojka (Peltigerales) is new to the canton of Graubunden. PMID- 26877565 TI - Terricolous Lichens in the Glacier Forefield of the Pasterze (Eastern Alps, Carinthia, Austria). AB - The investigation of lichens on soil, plant debris and terricolous mosses in the glacier forefield of the Pasterze yielded 35 lichen species. Placidiopsis oreades Breuss (Verrucariales) is new to Austria. Three sampling sites were established at increasing distance from the glacier, in order to compare species diversity, abundance and composition within the forefield and with four other glacier forefields of the Eastern Alps. PMID- 26877563 TI - Ophthalmic Manifestations of Amyotrophic Lateral Sclerosis (An American Ophthalmological Society Thesis). AB - PURPOSE: To determine if clinical and histopathologic findings were present in the eyes of patients with amyotrophic lateral sclerosis (ALS) and explore correlations to an animal model of ALS. METHODS: Two patients with ALS were studied histopathologically as well as the retinas of ALS/dementia transgenic mice with dysfunctional ubiquilin2, UBQLN2(P497H). Clinical study 1, an observational, cross-sectional study, was performed using optical coherence tomography (OCT) to obtain and compare mean total macular thickness and average and quadrant specific peripapillary retinal nerve fiber layer (pRNFL) scans from 16 patients with ALS to controls. Correlation analysis was performed to evaluate the association with disease duration. Clinical study 2 consisted of measuring visual acuity, color vision, contrast sensitivity, and quality of life in 12 patients. RESULTS: Histopathologic studies demonstrated intraretinal inclusions in one patient and loss of ganglion cell axons in another. Mouse eyes had intraretinal inclusions in the inner plexiform layers. Total macular volume was thinner in patients compared to controls (P<.05), and 37.5% of patients with ALS had an average pRNFL below the 1st percentile. Total macular and pRNFL thickness correlated inversely with disease duration. CONCLUSIONS: Histopathologic analysis of ALS eyes and mice with the UBQLN2(P497H) mutation, as well as OCT measurements, supports involvement of the anterior visual pathway. We identified pathologies, including intraretinal deposits and axonal loss. pRNFL and total macular thinning found on OCT correlated with disease duration. A pattern of vision loss specific for ALS was not identified. This study confirms ocular involvement in patients and transgenic animals with ALS/dementia. PMID- 26877567 TI - Popular Moralities and Institutional Rationalities in Malawi's Struggle Against AIDS. PMID- 26877566 TI - A Communicative Analysis of a Sexual Health Screening Intervention Conducted in a Low-income Housing Complex. AB - Providing free HIV screening within public housing sites offers the potential for increased participation of at-risk populations. Residential-based screening, however, raises concerns about privacy because of the stigma attached to HIV/AIDS and even to the testing for HIV. This study examined the effectiveness of offering HIV screening within a public housing high-rise in upstate New York. Through interviews with both women who obtained testing and those who did not, this study explored the tension between convenience and privacy concerns. The findings suggest that offering HIV screening where people live could encourage participation in the screenings, as well as lead to a destigmatization of HIV testing over time. Some women chose to eschew the convenience of on-site testing in favor of a more private venue for screening, whereas some women responded positively to the accessibility of on-site testing, using communicative strategies to manage privacy concerns. PMID- 26877568 TI - Slum Definitions in Urban India: Implications for the Measurement of Health Inequalities. AB - Half the population of low- and middle-income countries will live in urban areas by 2030, and poverty and inequality in these contexts is rising. Slum dwelling is one way in which to conceptualize and characterize urban deprivation but there are many definitions of what constitutes a slum. This paper presents four different slum definitions used in India alone, demonstrating that assessments of both the distribution and extent of urban deprivation depends on the way in which it is characterized, as does slum dwelling's association with common child health indicators. Using data from India's National Family and Health Survey from 2005 2006, two indictors of slum dwelling embedded in the survey and two constructed from the household questionnaire are compared using descriptive statistics and linear regression models of height- and weight-for-age z-scores. The results highlight a tension between international and local slum definitions, and underscore the importance of improving empirical representations of the dynamism of slum and city residents. PMID- 26877569 TI - CONDITIONAL DISTANCE CORRELATION. AB - Statistical inference on conditional dependence is essential in many fields including genetic association studies and graphical models. The classic measures focus on linear conditional correlations, and are incapable of characterizing non linear conditional relationship including non-monotonic relationship. To overcome this limitation, we introduces a nonparametric measure of conditional dependence for multivariate random variables with arbitrary dimensions. Our measure possesses the necessary and intuitive properties as a correlation index. Briefly, it is zero almost surely if and only if two multivariate random variables are conditionally independent given a third random variable. More importantly, the sample version of this measure can be expressed elegantly as the root of a V or U process with random kernels and has desirable theoretical properties. Based on the sample version, we propose a test for conditional independence, which is proven to be more powerful than some recently developed tests through our numerical simulations. The advantage of our test is even greater when the relationship between the multivariate random variables given the third random variable cannot be expressed in a linear or monotonic function of one random variable versus the other. We also show that the sample measure is consistent and weakly convergent, and the test statistic is asymptotically normal. By applying our test in a real data analysis, we are able to identify two conditionally associated gene expressions, which otherwise cannot be revealed. Thus, our measure of conditional dependence is not only an ideal concept, but also has important practical utility. PMID- 26877570 TI - The continuum disordered pinning model. AB - Any renewal processes on [Formula: see text] with a polynomial tail, with exponent [Formula: see text], has a non-trivial scaling limit, known as the [Formula: see text]-stable regenerative set. In this paper we consider Gibbs transformations of such renewal processes in an i.i.d. random environment, called disordered pinning models. We show that for [Formula: see text] these models have a universal scaling limit, which we call the continuum disordered pinning model (CDPM). This is a random closed subset of [Formula: see text] in a white noise random environment, with subtle features:Any fixed a.s. property of the [Formula: see text]-stable regenerative set (e.g., its Hausdorff dimension) is also an a.s. property of the CDPM, for almost every realization of the environment.Nonetheless, the law of the CDPM is singular with respect to the law of the [Formula: see text]-stable regenerative set, for almost every realization of the environment. The existence of a disordered continuum model, such as the CDPM, is a manifestation of disorder relevance for pinning models with [Formula: see text]. PMID- 26877571 TI - Trajectories of Perceived Social Support Among Low-Income Female Survivors of Hurricane Katrina. AB - The purpose of this study was to explore trajectories of perceived social support among low-income women who survived Hurricane Katrina, and were surveyed prior to the hurricane and approximately one and four years thereafter (N = 562). Latent class growth analysis provided evidence of four trajectories of perceived support: High Increasing (35.9%), High Decreasing (20.3%), Low Stable (41.1 %), and Low Decreasing (2.7%). Bereavement was significantly predictive of membership in the Low Stable trajectory, relative to the High Increasing and High Decreasing trajectories. Higher psychological distress and indicators of greater social network size, density and closeness were significantly predictive of membership in the Low Decreasing trajectory, relative to the High Increasing and High Decreasing trajectories. PMID- 26877572 TI - Suicidality, Economic Shocks, and Egalitarian Gender Norms. AB - Durkheim conceived of suicide as a product of social integration and regulation. Although the sociology of suicide has focused on the role of disintegration, to our knowledge, the interaction between integration and regulation has yet to be empirically evaluated. In this article we test whether more egalitarian gender norms, an important form of macro-regulation, protects men and women against suicidality during economic shocks. Using cross-national data covering 20 European Union countries from the years 1991 to 2011, including the recent economic crises in Europe, we first assessed the relation between unemployment and suicide. Then we evaluated potential effect modification using three measures of gender equality, the gender ratio in labour force participation, the gender pay gap, and women's representation in parliament using multiple measures. We found no evidence of a significant, direct link between greater gender equality and suicide rates in either men or women. However, a greater degree of gender equality helped protect against suicidality associated with economic shocks. At relatively high levels of gender equality in Europe, such as those seen in Sweden and Austria, the relationship between rising unemployment rates and suicide in men disappeared altogether. Our findings suggest that more egalitarian forms of gender regulation may help buffer the suicidal consequences of economic shocks, especially in men. PMID- 26877573 TI - Investigating Predictors of Listening Comprehension in Third-, Seventh-, and Tenth-Grade Students: A Dominance Analysis Approach. AB - This study rank ordered the contributive importance of several predictors of listening comprehension for third, seventh, and tenth graders. Principal components analyses revealed that a three-factor solution with fluency, reasoning, and working memory components provided the best fit across grade levels. Dominance analyses indicated that fluency and reasoning were the strongest predictors of third grade listening comprehension. Reasoning emerged as the strongest predictor of seventh and tenth grade listening comprehension. These findings suggest a shift in the contributive importance of predictors to listening comprehension across development (i.e., grade levels). The implications of our findings for educators and researchers are discussed. PMID- 26877574 TI - Selective Aromatic C-H Hydroxylation Enabled by eta6-Coordination to Iridium(III). AB - We report an aromatic C-H hydroxylation protocol in which the arene is activated through eta6-coordination to an iridium(III) complex. eta6-Coordination of the arene increases its electrophilicity and allows for high positional selectivity of hydroxylation at the site of least electron density. Through investigation of intermediate eta5-cyclohexadienyl adducts and arene exchange reactions, we evaluate incorporation of arene pi-activation into a catalytic cycle for C-H functionalization. PMID- 26877575 TI - Amide-Directed Formation of Five-Coordinate Osmium Alkylidenes from Alkynes. AB - The amide-directed synthesis of five-coordinate osmium alkylidene derivatives from alkynes is reported. These types of complexes, which have been elusive until now because of the tendency of osmium to give hydride alkylidyne species, are prepared by reaction of the dihydride OsH2Cl2(PiPr3)2 (1) with terminal alkynes containing a distal amide group. Complex 1 reacts with N-phenylhex-5-ynamide and N-phenylhepta-6-ynamide to give OsCl2{=C(CH3)(CH2) n NH(CO)Ph}(PiPr3)2 (n = 3 (2), 4 (3)). The relative position of carbonyl and NH groups in the organic substrates has no influence on the reaction. Thus, treatment of 1 with N-(pent-4 yn-1-yl)benzamide leads to OsCl2{=C(CH3)(CH2)3NHC(O)Ph}(PiPr3)2 (4). The new compounds are intermediate species in the cleavage of the C-C triple bond of the alkynes. Under mild conditions, they undergo the rupture of the Calpha-CH3 bond of the alkylidene, which comes from the alkyne triple bond, to afford six coordinate hydride-alkylidyne derivatives. In dichloromethane, complex 2 gives a 10:7 mixture of OsHCl2{=C(CH2)3C(O)NHPh}(PiPr3)2 (5) and OsHCl2{=CCH(CH3)(CH2)2C(O)NHPh}(PiPr3)2 (6). The first complex contains a linear separation between the alkylidyne Calpha atom and the amide group, whereas the spacer is branched in the second complex. In contrast to the case for 2, complex 4 selectively affords OsHCl2{=C(CH2)3NHC(O)Ph}(PiPr3)2 (7). In spite of their instability, these compounds give the alkylidene-allene metathesis, being a useful entry to five-coordinate vinylidene complexes, including the dicarbon disubstituted OsCl2(=C=CMe2)(PiPr3)2 (8) and the monosubstituted OsCl2(=C=CHCy)(PiPr3)2 (9). PMID- 26877576 TI - Non-mydriatic confocal retinal imaging using a digital light projector. AB - A digital light projector is implemented as an integrated illumination source and scanning element in a confocal non-mydriatic retinal camera, the Digital Light Ophthalmoscope (DLO). To simulate scanning, a series of illumination lines are rapidly projected on the retina. The backscattered light is imaged onto a 2 dimensional rolling shutter CMOS sensor. By temporally and spatially overlapping the illumination lines with the rolling shutter, confocal imaging is achieved. This approach enables a low cost, flexible, and robust design with a small footprint. The 3rd generation DLO technical design is presented, using a DLP LightCrafter 4500 and USB3.0 CMOS sensor. Specific improvements over previous work include the use of yellow illumination, filtered from the broad green LED spectrum, to obtain strong blood absorption and high contrast images while reducing pupil constriction and patient discomfort. PMID- 26877577 TI - Region-of-interest cone beam computed tomography (ROI CBCT) with a high resolution CMOS detector. AB - Cone beam computed tomography (CBCT) systems with rotational gantries that have standard flat panel detectors (FPD) are widely used for the 3D rendering of vascular structures using Feldkamp cone beam reconstruction algorithms. One of the inherent limitations of these systems is limited resolution (<3 lp/mm). There are systems available with higher resolution but their small FOV limits them to small animal imaging only. In this work, we report on region-of-interest (ROI) CBCT with a high resolution CMOS detector (75 MUm pixels, 600 MUm HR-CsI) mounted with motorized detector changer on a commercial FPD-based C-arm angiography gantry (194 MUm pixels, 600 MUm HL-CsI). A cylindrical CT phantom and neuro stents were imaged with both detectors. For each detector a total of 209 images were acquired in a rotational protocol. The technique parameters chosen for the FPD by the imaging system were used for the CMOS detector. The anti-scatter grid was removed and the incident scatter was kept the same for both detectors with identical collimator settings. The FPD images were reconstructed for the 10 cm x10 cm FOV and the CMOS images were reconstructed for a 3.84 cm * 3.84 cm FOV. Although the reconstructed images from the CMOS detector demonstrated comparable contrast to the FPD images, the reconstructed 3D images of the neuro stent clearly showed that the CMOS detector improved delineation of smaller objects such as the stent struts (~70 MUm) compared to the FPD. Further development and the potential for substantial clinical impact are suggested. PMID- 26877578 TI - Anti-scatter grid artifact elimination for high resolution x-ray imaging CMOS detectors. AB - Higher resolution in dynamic radiological imaging such as angiography is increasingly being demanded by clinicians; however, when standard anti-scatter grids are used with such new high resolution detectors, grid-line artifacts become more apparent resulting in increased structured noise that may overcome the contrast signal improvement benefits of the scatter-reducing grid. Although grid-lines may in theory be eliminated by dividing the image of a patient taken with the grid by a flat-field image taken with the grid obtained prior to the clinical image, unless the remaining additive scatter contribution is subtracted in real-time from the dynamic clinical image sequence before the division by the reference image, severe grid-line artifacts may remain. To investigate grid-line elimination, a stationary Smit Rontgen X-ray grid (line density: 70 lines/cm, grid ratio 13:1) was used with both a 75 micron-pixel CMOS detector and a standard 194 micron-pixel flat panel detector (FPD) to image an artery block insert placed in a modified uniform frontal head phantom for a 20 * 20cm FOV (approximately). Contrast and contrast-to-noise ratio (CNR) were measured with and without scatter subtraction prior to grid-line correction. The fixed pattern noise caused by the grid was substantially higher for the CMOS detector compared to the FPD and caused a severe reduction of CNR. However, when the scatter subtraction corrective method was used, the removal of the fixed pattern noise (grid artifacts) became evident resulting in images with improved CNR. PMID- 26877579 TI - Optimal-mass-transfer-based estimation of glymphatic transport in living brain. AB - It was recently shown that the brain-wide cerebrospinal fluid (CSF) and interstitial fluid exchange system designated the 'glymphatic pathway' plays a key role in removing waste products from the brain, similarly to the lymphatic system in other body organs1,2. It is therefore important to study the flow patterns of glymphatic transport through the live brain in order to better understand its functionality in normal and pathological states. Unlike blood, the CSF does not flow rapidly through a network of dedicated vessels, but rather through para-vascular channels and brain parenchyma in a slower time-domain, and thus conventional fMRI or other blood-flow sensitive MRI sequences do not provide much useful information about the desired flow patterns. We have accordingly analyzed a series of MRI images, taken at different times, of the brain of a live rat, which was injected with a paramagnetic tracer into the CSF via the lumbar intrathecal space of the spine. Our goal is twofold: (a) find glymphatic (tracer) flow directions in the live rodent brain; and (b) provide a model of a (healthy) brain that will allow the prediction of tracer concentrations given initial conditions. We model the liquid flow through the brain by the diffusion equation. We then use the Optimal Mass Transfer (OMT) approach3 to derive the glymphatic flow vector field, and estimate the diffusion tensors by analyzing the (changes in the) flow. Simulations show that the resulting model successfully reproduces the dominant features of the experimental data. PMID- 26877580 TI - Spatial distribution patterns of plague hosts: point pattern analysis of the burrows of great gerbils in Kazakhstan. AB - AIM: The spatial structure of a population can strongly influence the dynamics of infectious diseases, yet rarely is the underlying structure quantified. A case in point is plague, an infectious zoonotic disease caused by the bacterium Yersinia pestis. Plague dynamics within the Central Asian desert plague focus have been extensively modelled in recent years, but always with strong uniformity assumptions about the distribution of its primary reservoir host, the great gerbil (Rhombomys opimus). Yet, while clustering of this species' burrows due to social or ecological processes could have potentially significant effects on model outcomes, there is currently nothing known about the spatial distribution of inhabited burrows. Here, we address this knowledge gap by describing key aspects of the spatial patterns of great gerbil burrows in Kazakhstan. LOCATION: Kazakhstan. METHODS: Burrows were classified as either occupied or empty in 98 squares of four different sizes: 200 m (side length), 250 m, 500 m and 590-1020 m. We used Ripley's K statistic to determine whether and at what scale there was clustering of occupied burrows, and semi-variograms to quantify spatial patterns in occupied burrows at scales of 250 m to 9 km. RESULTS: Significant spatial clustering of occupied burrows occurred in 25% and 75% of squares of 500 m and 590-1020 m, respectively, but not in smaller squares. In clustered squares, the clustering criterion peaked around 250 m. Semi-variograms showed that burrow density was auto-correlated up to a distance of 7 km and occupied density up to 2.5 km. MAIN CONCLUSIONS: These results demonstrate that there is statistically significant spatial clustering of occupied burrows and that the uniformity assumptions of previous plague models should be reconsidered to assess its significance for plague transmission. This field evidence will allow for more realistic approaches to disease ecology models for both this system and for other structured host populations. PMID- 26877581 TI - How much flower-rich habitat is enough for wild pollinators? Answering a key policy question with incomplete knowledge. AB - In 2013, an opportunity arose in England to develop an agri-environment package for wild pollinators, as part of the new Countryside Stewardship scheme launched in 2015. It can be understood as a 'policy window', a rare and time-limited opportunity to change policy, supported by a narrative about pollinator decline and widely supported mitigating actions. An agri-environment package is a bundle of management options that together supply sufficient resources to support a target group of species. This paper documents information that was available at the time to develop such a package for wild pollinators. Four questions needed answering: (1) Which pollinator species should be targeted? (2) Which resources limit these species in farmland? (3) Which management options provide these resources? (4) What area of each option is needed to support populations of the target species? Focussing on wild bees, we provide tentative answers that were used to inform development of the package. There is strong evidence that floral resources can limit wild bee populations, and several sources of evidence identify a set of agri-environment options that provide flowers and other resources for pollinators. The final question could only be answered for floral resources, with a wide range of uncertainty. We show that the areas of some floral resource options in the basic Wild Pollinator and Farmland Wildlife Package (2% flower-rich habitat and 1 km flowering hedgerow), are sufficient to supply a set of six common pollinator species with enough pollen to feed their larvae at lowest estimates, using minimum values for estimated parameters where a range was available. We identify key sources of uncertainty, and stress the importance of keeping the Package flexible, so it can be revised as new evidence emerges about how to achieve the policy aim of supporting pollinators on farmland. PMID- 26877582 TI - Variable Selection and Inference Procedures for Marginal Analysis of Longitudinal Data with Missing Observations and Covariate Measurement Error. AB - In contrast to extensive attention on model selection for univariate data, research on model selection for longitudinal data remains largely unexplored. This is particularly the case when data are subject to missingness and measurement error. To address this important problem, we propose marginal methods that simultaneously carry out model selection and estimation for longitudinal data with missing responses and error-prone covariates. Our method have several appealing features: the applicability is broad because the methods are developed for a unified framework with marginal generalized linear models; model assumptions are minimal in that no full distribution is required for the response process and the distribution of the mismeasured covariates is left unspecified; and the implementation is straightforward. To justify the proposed methods, we provide both theoretical properties and numerical assessments. PMID- 26877583 TI - Getting Grandma Online: Are Tablets the Answer for Increasing Digital Inclusion for Older Adults in the U.S.? AB - Using information and communication technologies (ICTs) can improve older adults' quality of life. ICT use is associated with decreased feelings of loneliness and depression, along with increased feelings of independence and personal growth. However, limited access and low technological self-efficacy are key reasons why some groups, especially older adults, are excluded from being fully engaged in the digital world. In this study, we focus on older adults' technological self efficacy, which is related to their actual use of technology and the second level digital divide. Specifically, we examine: 1) how older adults decide to use a new technology, tablet computers; 2) how they conquer the barrier of technological self-efficacy through using tablets; and 3) the impacts of using this new technology in their lives. Twenty-one in-depth interviews were conducted with older adults residing in independent living communities in a medium-sized city in the Deep South region of the United States. Observational and enactive learning played important roles for older adults in using tablets. Seeing others use tablets, getting recommendations from family members, or having tablets given to them were the primary reasons they started to use tablet computers. The ease of use feature of tablets helped solve the problem of lacking technological self efficacy. Using tablets helped increase a sense of connectedness. Tablet computers may be one way to increase digital inclusion among older adults. PMID- 26877584 TI - The emotional responses of browsing Facebook: Happiness, envy, and the role of tie strength. AB - On Facebook, users are exposed to posts from both strong and weak ties. Even though several studies have examined the emotional consequences of using Facebook, less attention has been paid to the role of tie strength. This paper aims to explore the emotional outcomes of reading a post on Facebook and examine the role of tie strength in predicting happiness and envy. Two studies - one correlational, based on a sample of 207 American participants and the other experimental, based on a sample of 194 German participants - were conducted in 2014. In Study 2, envy was further distinguished into benign and malicious envy. Based on a multi-method approach, the results showed that positive emotions are more prevalent than negative emotions while browsing Facebook. Moreover, tie strength is positively associated with the feeling of happiness and benign envy, whereas malicious envy is independent of tie strength after reading a (positive) post on Facebook. PMID- 26877585 TI - Variation of Select Flavonols and Chlorogenic Acid Content of Elderberry Collected Throughout the Eastern United States. AB - American elderberries are commonly collected from wild plants for use as food and medicinal products. The degree of phytochemical variation amongst wild populations has not been established and might affect the overall quality of elderberry dietary supplements. The three major flavonols identified in elderberries are rutin, quercetin and isoquercetin. Variation in the flavonols and chlorogenic acid was determined for 107 collections of elderberries from throughout the eastern United States using an optimized high performance liquid chromatography with ultraviolet detection method. The mean content was 71.9 mg per 100g fresh weight with variation ranging from 7.0 to 209.7 mg per 100 g fresh weight within the collected population. Elderberries collected from southeastern regions had significantly higher contents in comparison with those in more northern regions. The variability of the individual flavonol and chlorogenic acid profiles of the berries was complex and likely influenced by multiple factors. Several outliers were identified based on unique phytochemical profiles in comparison with average populations. This is the first study to determine the inherent variability of American elderberries from wild collections and can be used to identify potential new cultivars that may produce fruits of unique or high-quality phytochemical content for the food and dietary supplement industries. PMID- 26877586 TI - Rats time long intervals: Evidence from several cases. AB - Long-interval timing fills the gap between the traditional range of short interval timing (i.e., seconds to minutes) and the limited range of circadian entrainment (i.e., approximately a day). A number of reports suggest that rats time long intervals. However, a recent report proposed that anticipation of long, but noncircadian, intervals is highly constrained. We tested the hypothesis that long-interval timing is highly constrained by examining a number of cases: 7, 8, 9, 11, 12, and 13 hour intermeal intervals. We found evidence for long-interval timing in each case. Long-interval timing appears to be robust. PMID- 26877587 TI - Fit Assessment of N95 Filtering-Facepiece Respirators in the U.S. Centers for Disease Control and Prevention Strategic National Stockpile. AB - National Institute for Occupational Safety and Health (NIOSH)-approved N95 filtering-facepiece respirators (FFR) are currently stockpiled by the U.S. Centers for Disease Control and Prevention (CDC) for emergency deployment to healthcare facilities in the event of a widespread emergency such as an influenza pandemic. This study assessed the fit of N95 FFRs purchased for the CDC Strategic National Stockpile. The study addresses the question of whether the fit achieved by specific respirator sizes relates to facial size categories as defined by two NIOSH fit test panels. Fit test data were analyzed from 229 test subjects who performed a nine-donning fit test on seven N95 FFR models using a quantitative fit test protocol. An initial respirator model selection process was used to determine if the subject could achieve an adequate fit on a particular model; subjects then tested the adequately fitting model for the nine-donning fit test. Only data for models which provided an adequate initial fit (through the model selection process) for a subject were analyzed for this study. For the nine donning fit test, six of the seven respirator models accommodated the fit of subjects (as indicated by geometric mean fit factor > 100) for not only the intended NIOSH bivariate and PCA panel sizes corresponding to the respirator size, but also for other panel sizes which were tested for each model. The model which showed poor performance may not be accurately represented because only two subjects passed the initial selection criteria to use this model. Findings are supportive of the current selection of facial dimensions for the new NIOSH panels. The various FFR models selected for the CDC Strategic National Stockpile provide a range of sizing options to fit a variety of facial sizes. PMID- 26877589 TI - The Year of the Wise Monkeys. PMID- 26877588 TI - Where do College Drinkers Draw the Line? A Qualitative Study. AB - Alcohol use among college students has received nationwide recognition as a public health concern. The primary aim of this study was to explore students' opinions of when drinking "crosses the line" from acceptable to unacceptable. This study used qualitative methods to: (a) examine unappealing aspects of drinking by relationship type (potential dating partner, friend, self), and (b) determine whether this differs by gender. Seventy-eight interviews were conducted with college students who violated campus-alcohol policy. The semi-structured interview included open-ended questions related to reactions to other's excessive drinking. Qualitative analyses revealed that college males and females find lack of control as unappealing, including lack of physical, verbal, and sexual control. More females than males indicated negative perceptions of same-sex friends and self who displayed poor sexual control. Future research might also consider integration of themes in measures of negative expectancies and consequences to more accurately capture unappealing aspects of college drinking behavior. PMID- 26877590 TI - The efficacy of laser-assisted in-office bleaching and home bleaching on sound and demineralized enamel. AB - AIMS: This study investigated the effectiveness of laser-assisted in-office bleaching and home-bleaching in sound and demineralized enamel. MATERIALS AND METHODS: The sample consisted of 120 freshly-extracted bovine incisors. Half of the specimens were stored in a demineralizing solution to induce white spot lesions. Following exposure to a tea solution for 7.5 days, the specimens were randomly assigned to 4 groups of 30 according to the type of enamel and the bleaching procedure employed. Groups 1 and 2 consisted of demineralized teeth subjected to in-office bleaching and home bleaching, whereas in groups 3 and 4, sound teeth were subjected to in-office and home bleaching, respectively. A diode laser (810 nm, 2 W, continuous wave, four times for 15 seconds each) was employed for assisting the in-office process. The color of the specimens was measured before (T1) and after (T2) staining and during (T3) and after (T4) the bleaching procedures using a spectrophotometer. The color change (DeltaE) between different treatments stages was compared among the groups. RESULTS: There were significant differences in the color change between T2 and T3 (DeltaE T2-T3) and T2 and T4 (DeltaE T2-T4) stages among the study groups (p<0.05). Pairwise comparison by Duncan test revealed that both DeltaET2-T3 and DeltaET2-T4 were significantly greater in demineralized teeth submitted to laser-assisted in-office bleaching (group 1) as compared to the other groups (P< 0.05). CONCLUSION: Laser-assisted in-office bleaching could provide faster and greater whitening effect than home bleaching on stained demineralized enamel, but both procedures produced comparable results on sound teeth. PMID- 26877591 TI - 405 nm diode laser, halogen lamp and LED device comparison in dental composites cure: an "in vitro" experimental trial. AB - BACKGROUND AND AIMS: A 405 nm diode laser is indicated for composite materials polymerizing, thanks to the recent evolution in their compositions, absorbing in blue part of the spectrum. The purpose of this research was to evaluate its performance on two different kinds of composite resins. MATERIALS AND METHODS: Two different composites were polymerized with a traditional halogen lamp, a LED device and a 405 nm diode laser. The depth of the cure, the volumetric shrinkage, and the degree of the conversion (DC%) of the double bond during the curing process were measured. One-way ANOVA test, Kruskal-Wallis tests, and Dunn comparison tests were used for statistic analysis. RESULTS: Regarding the depth of polymerization, the laser had the worst performance on one composite while on the other, no significant difference with the other devices was observed. The volumetric shrinkage showed that laser produced the lowest change in both of the composites. The DC% measure confirmed these findings. CONCLUSIONS: Based on the results of this preliminary study, it is not possible to recommend the 405 nm diode laser for the polymerization of dental composites. PMID- 26877592 TI - Adjunctive 830 nm light-emitting diode therapy can improve the results following aesthetic procedures. AB - BACKGROUND: Aggressive, or even minimally aggressive, aesthetic interventions are almost inevitably followed by such events as discomfort, erythema, edema and hematoma formation which could lengthen patient downtime and represent a major problem to the surgeon. Recently, low level light therapy with light-emitting diodes (LED-LLLT) at 830 nm has attracted attention in wound healing indications for its anti-inflammatory effects and control of erythema, edema and bruising. RATIONALE: The wavelength of 830 nm offers deep penetration into living biological tissue, including bone. A new-generation of 830 nm LEDs, based on those developed in the NASA Space Medicine Laboratory, has enabled the construction of planar array-based LED-LLLT systems with clinically useful irradiances. Irradiation with 830 nm energy has been shown in vitro and in vivo to increase the action potential of epidermal and dermal cells significantly. The response of the inflammatory stage cells is enhanced both in terms of function and trophic factor release, and fibroblasts demonstrate superior collagenesis and elastinogenesis. CONCLUSIONS: A growing body of clinical evidence is showing that applying 830 nm LED-LLLT as soon as possible post-procedure, both invasive and noninvasive, successfully hastens the resolution of sequelae associated with patient downtime in addition to significantly speeding up frank wound healing. This article reviews that evidence, and attempts to show that 830 nm LED-LLLT delivers swift resolution of postoperative sequelae, minimizes downtime and enhances patient satisfaction. PMID- 26877594 TI - Influence of diffuse reflectance measurement accuracy on the scattering coefficient in determination of optical properties with integrating sphere optics (a secondary publication). AB - An estimation error of the scattering coefficient of hemoglobin in the high absorption wavelength range has been observed in optical property calculations of blood-rich tissues. In this study, the relationship between the accuracy of diffuse reflectance measurement in the integrating sphere and calculated scattering coefficient was evaluated with a system to calculate optical properties combined with an integrating sphere setup and the inverse Monte Carlo simulation. Diffuse reflectance was measured with the integrating sphere using a small incident port diameter and optical properties were calculated. As a result, the estimation error of the scattering coefficient was improved by accurate measurement of diffuse reflectance. In the high absorption wavelength range, the accuracy of diffuse reflectance measurement has an effect on the calculated scattering coefficient. PMID- 26877593 TI - Evolution of the role of phototherapy during endodontic decontamination. AB - A microbe free root canal space before obturation leads to higher success rate and conventional chemo-mechanical debridement might not achieve this goal completely. First trials of laser in dentistry started from surgical intervention on caries and bones of oral cavity and extended to prepare cavities and even shaping root canals. Afterward lasers were implicated soon into direct debridement of root canal space. Anyhow failure of laser to remove debris totally from root canal space is demonstrated recently, additionally it might lead to damages to surrounding tissues or inorganic material of root canal if be used without precaution. Nowadays the theory of light assisted protocols became another start point for laser in endodontics. Laser has been introduced as an adjuvant to conventional debridement of root canals. We used Medline search engine to collect scientific publications to edit this review article in purpose of revealing the evolution of laser position from an ultimate cleaning methodology to an adjuvant to conventional root canal disinfection protocols. PMID- 26877595 TI - Dialect variation, dialect-shifting, and reading comprehension in second grade. AB - The purpose of this study was to examine second graders' (n=680) changing spoken nonmainstream American English (NMAE) use in relation to their oral language and reading comprehension achievement. Fall NMAE production was negatively associated with fall achievement scores. NMAE production generally decreased from fall to spring. Students who qualified for the US Free and Reduced Lunch program (FARL) and who had stronger language skills were more likely to decrease their NMAE use (i.e., dialect shifting) than their peers who did not qualify for FARL or their peers with weaker language skills. Dialect shifting for a sub-sample of 102 students who used substantial amounts of NMAE at the beginning of the school year was predicted by school context, controlling for reading and language skills - in general, students who attended more affluent schools dialect shifted to a greater extent than did their peers who attended higher poverty schools. Greater dialect shifting in this group predicted gains in reading comprehension from fall to spring. PMID- 26877596 TI - ALD grown bilayer junction of ZnO:Al and tunnel oxide barrier for SIS solar cell. AB - Various metal oxides are probed as extrinsic thin tunnel barriers in Semiconductor Insulator Semiconductor solar cells. Namely Al2O3, ZrO2, Y2O3, and La2O3 thin films are in between n-type ZnO:Al (AZO) and p-type Si substrates by means of Atomic Layer Deposition. Low reverse dark current-density as low as 3*10 7 A/cm2, a fill factor up to 71.3%, and open-circuit voltage as high as 527 mV are obtained, achieving conversion efficiency of 8% for the rare earth oxide La2O3. ZrO2 and notably Al2O3 show drawbacks in performance suggesting an adverse reactivity with AZO as also indicated by X-ray Photoelectron Spectroscopy. PMID- 26877597 TI - Maternal Religiosity, Family Resources and Stressors, and Parent-Child Attachment Security in Northern Ireland. AB - This study explores the associations between mothers' religiosity, and families' and children's functioning in a stratified random sample of 695 Catholic and Protestant mother-child dyads in socially deprived areas in Belfast, Northern Ireland, a region which has experienced centuries of sectarian conflict between Protestant Unionists and Catholics Nationalists. Findings based on mother and child surveys indicated that even in this context of historical political violence associated with religious affiliation, mothers' religiosity played a consistently positive role, including associations with multiple indicators of better family functioning (i.e., more cohesion and behavioral control and less conflict, psychological distress, and adjustment problems) and greater parent child attachment security. Mothers' religiosity also moderated the association between parent-child attachment security and family resources and family stressors, enhancing positive effects of cohesion and mother behavioral control on mother-child attachment security, and providing protection against risks associated with mothers' psychological distress. Findings are discussed in terms of implications for understanding the role of religiosity in serving as a protective or risk factor for children and families. PMID- 26877598 TI - Spatially Modelling the Association Between Access to Recreational Facilities and Exercise: The 'Multi-Ethnic Study of Atherosclerosis'. AB - Numerous studies have investigated the relationship between the built environment and physical activity. However these studies assume that these relationships are invariant over space. In this study, we introduce a novel method to analyze the association between access to recreational facilities and exercise allowing for spatial heterogeneity. In addition, this association is studied before and after controlling for crime, a variable that could explain spatial heterogeneity of associations. We use data from the Chicago site of the Multi-Ethnic Study of Atherosclerosis of 781 adults aged 46 years and over. A spatially varying coefficient Tobit regression model is implemented in the Bayesian setting to allow for the association of interest to vary over space. The relationship is shown to vary over Chicago, being positive in the south but negative or null in the north. Controlling for crime weakens the association in the south with little change observed in northern Chicago. The results of this study indicate that spatial heterogeneity in associations of environmental factors with health may vary over space and deserve further exploration. PMID- 26877600 TI - Surveillance of colonic polyps: Are we getting it right? AB - Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. The identification of colonic polyps can reduce CRC mortality through earlier diagnosis of cancers and the removal of polyps: the precursor lesion of CRC. Following the finding and removal of colonic polyps at an initial colonoscopy, some patients are at an increased risk of developing CRC in the future. This is the rationale for post-polypectomy surveillance colonoscopy. However, not all individuals found to have colonic adenomas have a risk of CRC higher than that of the general population. This review examines the literature on post-polypectomy surveillance including current international clinical guidelines. The potential benefits of surveillance procedures must be weighed against the burden of colonoscopy: resource use, the potential for patient discomfort, and the risk of complications. Therefore surveillance colonoscopy is best utilised in a selected group of individuals at a high risk of developing cancer. Further study is needed into the specific factors conferring higher risk as well as the efficacy of surveillance in mitigating this risk. Such evidence will better inform clinicians and patients of the relative benefits of colonoscopic surveillance for the individual. In addition, the decision to continue with surveillance must be informed by the changing profile of risks and benefits of further procedures with the patient's advancing age. PMID- 26877601 TI - Combined locoregional treatment of patients with hepatocellular carcinoma: State of the art. AB - In recent years, a combination of intervention therapies has been widely applied in the treatment of hepatocellular carcinoma (HCC). One such combined strategy is based on the combination of the percutaneous approach, such as radiofrequency ablation (RFA), and the intra-arterial locoregional approach, such as trans arterial chemoembolization (TACE). Several types of evidence have supported the feasibility and benefit of combined therapy, despite some studies reporting conflicting results and outcomes. The aim of this review was to explain the technical aspects of different combined treatments and to comprehensively analyze and compare the clinical efficacy and safety of this combined treatment option and monotherapy, either as TACE or RFA alone, in order to provide clinicians with an unbiased opinion and valuable information. Based on a literature review and our experience, combined treatment seems to be a safe and effective option in the treatment of patients with early/intermediate HCC when surgical resection is not feasible; furthermore, this approach provides better results than RFA and TACE alone for the treatment of large HCC, defined as those exceeding 3 cm in size. It can also expand the indication for RFA to previously contraindicated "complex cases", with increased risk of thermal ablation related complications due to tumor location, or to "complex patients" with high bleeding risk. PMID- 26877599 TI - Mechanism and Function of Angiogenin in Hematopoietic Malignancy. AB - Angiogenic factors have been widely implicated in the formation and progression of solid tumors. A number of angiogenic mediators have been recently appreciated as having equivalent function in non-solid tumors, such as leukemia. One such factor, angiogenin (ANG), promotes tumor cell growth and angiogenesis in solid cancers; however its precise function(s) in hematological disorders are not fully understood. This review summarizes current knowledge of the function and therapeutic potential of angiogenic factors, with particular emphasis on the role and hypothesized mechanism of ANG in a non-solid tumor setting. PMID- 26877602 TI - Hepatocellular carcinoma and hepatitis B surface protein. AB - The tumorigenesis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) has been widely studied. HBV envelope proteins are important for the structure and life cycle of HBV, and these proteins are useful for judging the natural disease course and guiding treatment. Truncated and mutated preS/S are produced by integrated viral sequences that are defective for replication. The preS/S mutants are considered "precursor lesions" of HCC. Different preS/S mutants induce various mechanisms of tumorigenesis, such as transactivation of transcription factors and an immune inflammatory response, thereby contributing to HCC. The preS2 mutants and type II "Ground Glass" hepatocytes represent novel biomarkers of HBV-associated HCC. The preS mutants may induce the unfolded protein response and endoplasmic reticulum stress-dependent and stress independent pathways. Treatments to inhibit hepatitis B surface antigen (HBsAg) and damage secondary to HBsAg or the preS/S mutants include antivirals and antioxidants, such as silymarin, resveratrol, and glycyrrhizin acid. Methods for the prevention and treatment of HCC should be comprehensive. PMID- 26877604 TI - Anti-rods/rings autoantibody generation in hepatitis C patients during interferon alpha/ribavirin therapy. AB - Chronic inflammation associated with hepatitis C virus (HCV) infection can lead to disabling liver diseases with progression to liver cirrhosis and hepatocellular carcinoma. Despite the recent availability of more effective and less toxic therapeutic options, in most parts of the world the standard treatment consists of a weekly injection of pegylated interferon alpha (IFN-alpha) together with a daily dose of ribavirin. HCV patients frequently present circulating non organ-specific autoantibodies demonstrating a variety of staining patterns in the indirect immunofluorescence assay for antinuclear antibodies (ANA). Between 20% to 40% of HCV patients treated with IFN-alpha and ribavirin develop autoantibodies showing a peculiar ANA pattern characterized as rods and rings (RR) structures. The aim of this article is to review the recent reports regarding RR structures and anti-rods/rings (anti-RR) autoantibody production by HCV patients after IFN-alpha/ribavirin treatment. Anti-RR autoantibodies first appear around the sixth month of treatment and reach a plateau around the twelfth month. After treatment completion, anti-RR titers decrease/disappear in half the patients and remain steady in the other half. Some studies have observed a higher frequency of anti-RR antibodies in relapsers, i.e., patients in which circulating virus reappears after initially successful therapy. The main target of anti-RR autoantibodies in HCV patients is inosine-5'-monophosphate dehydrogenase 2 (IMPDH2), the rate-limiting enzyme involved in the guanosine triphosphate biosynthesis pathway. Ribavirin is a direct IMPDH2 inhibitor and is able to induce the formation of RR structures in vitro and in vivo. In conclusion, these observations led to the hypothesis that anti-RR autoantibody production is a human model of immunologic tolerance breakdown that allows us to explore the humoral autoimmune response from the beginning of the putative triggering event: exposure to ribavirin and interferon. PMID- 26877603 TI - Hepatitis C virus relies on lipoproteins for its life cycle. AB - Hepatitis C virus (HCV) infects over 150 million people worldwide. In most cases, HCV infection becomes chronic causing liver disease ranging from fibrosis to cirrhosis and hepatocellular carcinoma. Viral persistence and pathogenesis are due to the ability of HCV to deregulate specific host processes, mainly lipid metabolism and innate immunity. In particular, HCV exploits the lipoprotein machineries for almost all steps of its life cycle. The aim of this review is to summarize current knowledge concerning the interplay between HCV and lipoprotein metabolism. We discuss the role played by members of lipoproteins in HCV entry, replication and virion production. PMID- 26877607 TI - Portopulmonary hypertension in liver transplant candidates. AB - Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed. PMID- 26877606 TI - Coagulopathy and transfusion therapy in pediatric liver transplantation. AB - Bleeding and coagulopathy are critical issues complicating pediatric liver transplantation and contributing to morbidity and mortality in the cirrhotic child. The complexity of coagulopathy in the pediatric patient is illustrated by the interaction between three basic models. The first model, "developmental hemostasis", demonstrates how a different balance between pro- and anticoagulation factors leads to a normal hemostatic capacity in the pediatric patient at various ages. The second, the "cell based model of coagulation", takes into account the interaction between plasma proteins and cells. In the last, the concept of "rebalanced coagulation" highlights how the reduction of both pro- and anticoagulation factors leads to a normal, although unstable, coagulation profile. This new concept has led to the development of novel techniques used to analyze the coagulation capacity of whole blood for all patients. For example, viscoelastic methodologies are increasingly used on adult patients to test hemostatic capacity and to guide transfusion protocols. However, results are often confounding or have limited impact on morbidity and mortality. Moreover, data from pediatric patients remain inadequate. In addition, several interventions have been proposed to limit blood loss during transplantation, including the use of antifibrinolytic drugs and surgical techniques, such as the piggyback and lowering the central venous pressure during the hepatic dissection phase. The rationale for the use of these interventions is quite solid and has led to their incorporation into clinical practice; yet few of them have been rigorously tested in adults, let alone in children. Finally, the postoperative period in pediatric cohorts of patients has been characterized by an enhanced risk of hepatic vessel thrombosis. Thrombosis in fact remains the primary cause of early graft failure and re-transplantation within the first 30 d following surgery, and it occurs despite prolongation of standard coagulation assays. Data, however, are currently lacking regarding the use of anti aggregation/anticoagulation therapies and how to best monitor for thrombosis in the early postoperative period in pediatric patients. Therefore, further studies are necessary to elucidate the interaction between the development of the coagulation system and cirrhosis in children. Moreover, strategies to optimize blood transfusion and anticoagulation must be tested specifically in pediatric patients. In conclusion, data from the adult world can be translated with difficulty into the pediatric field as indication for transplantation, baseline pathologies and levels of pro- and anticoagulation factors are not comparable between the two populations. PMID- 26877605 TI - Laparoscopic and robot-assisted laparoscopic digestive surgery: Present and future directions. AB - Laparoscopic surgery is applied today worldwide to most digestive procedures. In some of them, such as cholecystectomy, Nissen's fundoplication or obesity surgery, laparoscopy has become the standard in practice. In others, such as colon or gastric resection, the laparoscopic approach is frequently used and its usefulness is unquestionable. More complex procedures, such as esophageal, liver or pancreatic resections are, however, more infrequently performed, due to the high grade of skill necessary. As a result, there is less clinical evidence to support its implementation. In the recent years, robot-assisted laparoscopic surgery has been increasingly applied, again with little evidence for comparison with the conventional laparoscopic approach. This review will focus on the complex digestive procedures as well as those whose use in standard practice could be more controversial. Also novel robot-assisted procedures will be updated. PMID- 26877608 TI - Cytomegalovirus and ulcerative colitis: Place of antiviral therapy. AB - The link between cytomegalovirus (CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis (UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools (numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flare-ups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease. PMID- 26877609 TI - Glucose metabolism in gastric cancer: The cutting-edge. AB - Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID- 26877610 TI - hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis. AB - AIM: To investigate the expression profiles of hsa-miR-29c and hsa-miR-135b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-miR-29c and hsa-miR-135b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinal-type gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-miR-29c and hsa-miR-135b expression profiles in the grouped samples was evaluated by ANOVA and Student's t-test tests. The results were adjusted for multiple testing by using Bonferroni's correction. P values <= 0.05 were considered statistically significant. To evaluate hsa-miR-29c and hsa miR-135b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-miR-29c and hsa-miR-135b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis. RESULTS: The expression levels of hsa-miR-29c were higher in normal gastric mucosal samples, and decreased progressively in non atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal type gastric adenocarcinoma samples. The expression of hsa-miR-29c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This microRNA (miRNA) has a good discriminatory accuracy between normal gastric samples and (1) intestinal-type gastric adenocarcinoma; and (2) intestinal metaplasia, and regulates the DMNT3A oncogene. hsa-miR-135b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-miR-135b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This miRNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes. CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-miR-29c and hsa-miR-135b are promising biomarkers of gastric carcinogenesis. PMID- 26877611 TI - Oncogenic potential of IDH1R132C mutant in cholangiocarcinoma development in mice. AB - AIM: To investigate whether IDH1R132C mutant in combination with loss of p53 and activated Notch signaling promotes intrahepatic cholangiocarcinoma (ICC) development. METHODS: We applied hydrodynamic injection and sleeping beauty mediated somatic integration to induce loss of p53 (via shP53), activation of Notch [via intracellular domain of Notch1 (NICD)] and/or overexpression of IDH1R132C mutant together with the sleeping beauty transposase into the mouse liver. Specifically, we co-expressed shP53 and NICD (shP53/NICD, n = 4), shP53 and IDH1R132C (shP53/IDH1R132C, n = 3), NICD and IDH1R132C (NICD/IDH1R132C, n = 4), as well as NICD, shP53 and IDH1R132C (NICD/shP53/IDH1R132C, n = 9) in mice. Mice were monitored for liver tumor development and euthanized at various time points. Liver histology was analyzed by hematoxylin and eosin staining. Molecular features of NICD/shP53/IDH1R132C ICC tumor cells were characterized by Myc tag, Flag tag, Ki-67, p-Erk and p-AKT immunohistochemical staining. Desmoplastic reaction in tumor tissues was studied by Picro-Sirius red staining. RESULTS: We found that co-expression of shP53/NICD, shP53/IDH1R132C or NICD/IDH1R132C did not lead to liver tumor formation. In striking contrast, co-expression of NICD/shP53/IDH1R132C resulted in ICC development in mice (P < 0.01). The tumors could be identified as early as 12 wk post hydrodynamic injection. Tumors rapidly progressed, and by 18 wk post hydrodynamic injection, multiple cystic lesions could be identified on the liver surface. NICD/shP53/IDH1R132C liver tumors shared multiple histological features of human ICCs, including hyperplasia of irregular glands. Importantly, all tumor cells were positive for the biliary epithelial cell marker cytokeratin 19. Extensive collagen fibers could be visualized in tumor tissues using Sirus red staining, duplicating the desmoplastic reaction observed in human ICC. Tumors were highly proliferative and expressed ectopically injected genes. Together these studies supported that NICD/shP53/IDH1R132C liver tumors were indeed ICCs. Finally, no p-AKT or p-ERK positive staining was observed, suggesting that NICD/shP53/IDH1R132C driven ICC development was independent of AKT/mTOR and Ras/MAPK signaling cascades. CONCLUSION: We have generated a simple, non-germline murine ICC model with activated Notch, loss of p53 and IDH1R132C mutant. The study supported the oncogenic potential of IDH1R132C. PMID- 26877612 TI - Interleukin-22 contributes to liver regeneration in mice with concanavalin A induced hepatitis after hepatectomy. AB - AIM: To investigate the therapeutic effects and mechanisms of interleukin (IL)-22 in liver regeneration in mice with concanavalin A (ConA)-induced liver injury following 70% hepatectomy. METHODS: Mice were injected intravenously with ConA at 10 MUg/g body weight 4 d before 70% hepatectomy to create a hepatitis model, and recombinant IL-22 was injected at 0.125 MUg/g body weight 30 min prior to 70% hepatectomy to create a therapy model. Control animals received an intravenous injection of an identical volume of normal saline. RESULTS: IL-22 treatment prior to 70% hepatectomy performed under general anesthesia resulted in reductions in the biochemical and histological evidence of liver injury, earlier proliferating cell nuclear antigen expression and accelerated recovery of liver mass. IL-22 pretreatment also significantly induced signal transducer and activator of transcription factor 3 (STAT3) activation and increased the expression of a variety of mitogenic proteins, such as Cyclin D1. Furthermore, alpha fetal protein mRNA expression was significantly elevated after IL-22 treatment. CONCLUSION: In this study, we demonstrated that IL-22 is a survival factor for hepatocytes and prevents and repairs liver injury by enhancing pro-growth pathways via STAT3 activation. Treatment with IL-22 protein may represent a novel therapeutic strategy for preventing liver injury in patients with liver disease who have undergone hepatectomy. PMID- 26877613 TI - Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway. AB - AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) with human urokinase-type plasminogen activator (uPA) on liver fibrosis, and to investigate the mechanism of gene therapy. METHODS: BMSCs transfected with adenovirus-mediated human urokinase plasminogen activator (Ad uPA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and mRNA expression levels. RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type III were markedly decreased, whereas the levels of serum albumin were increased by uPA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while uPA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area (16.69% +/- 1.30%), while fibrotic area was significantly decreased by BMSCs treatment (12.38% +/- 2.27%) and was further reduced by uPA-BMSCs treatment (8.31% +/- 1.21%). Both protein and mRNA expression of beta-catenin, Wnt4 and Wnt5a was down-regulated in liver tissues following uPA gene modified BMSCs treatment when compared with the model animals. CONCLUSION: Transplantation of uPA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with uPA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway. PMID- 26877614 TI - Prospective evaluation of the cause of acute pancreatitis, with special attention to medicines. AB - AIM: To investigate the cause of acute pancreatitis (AP) by conducting a thorough investigation of drugs and their possible etiological role. METHODS: We investigated the cause of AP in a large retrospective cohort of 613 adult patients admitted with AP at the Akershus University Hospital, Norway, from 2000 until 2009, who were evaluated with standard ward investigations. This group was compared with a prospectively evaluated group (n = 57) admitted from January 2010 until September 2010 who investigated more extensively using medical history and radiological assessment. RESULTS: The groups were comparable with regards to gender, age, comorbidity and severity. The most common etiology was bile stones and alcohol, occurring in 60% in both groups. The prospective group was examined more thoroughly with regards to the use of alcohol and medicines. An increased number of radiological investigations during hospital stay and at follow-up were also performed. A more extensive use of radiological evaluation did not increase the detection frequency of bile stones. In the prospective group, more than half of the patients had two or more possible causes of pancreatitis, being mostly a combination of bile stones and drugs. No possible cause was found in only 3.5% of these patients, compared with 29.7% in the retrospective group. CONCLUSION: A detailed medical history and extensive radiological evaluation may determine a possible etiology in almost all cases of AP. Many patients have several possible risk factors, and uncertainty remains in establishing the definitive etiology. PMID- 26877615 TI - Response to strict and liberalized specific carbohydrate diet in pediatric Crohn's disease. AB - AIM: To investigate the specific carbohydrate diet (SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease (CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple (diet alone, antibiotics or 5-ASA) or SCD with immunomodulators (corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics. RESULTS: The mean age at start of the SCD was 11.8 +/- 3.0 years (range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 +/- 4.0 mo (range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization (P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth. PMID- 26877616 TI - Healthcare and economic impact of diarrhea in patients with carcinoid syndrome. AB - AIM: To examine healthcare resource utilization patterns and costs accrued by carcinoid syndrome (CS) patients with and without diarrhea. METHODS: We conducted a retrospective cohort study using MarketScan(r) data from 1/1/2002-12/31/2012. Newly diagnosed CS patients had 1 medical claim for CS (ICD-9-CM code 259.2) plus either >= 1 additional claim for CS or for carcinoid tumors (ICD-9-CM 209.x), and had no evidence of CS for 1 year prior to index CS diagnosis, in commercially insured patients < 65 years old. Patients were required to have continuous enrollment one year prior and after index date (first claim with CS diagnosis in the ID period). We identified patients with evidence of non-infectious diarrhea (ICD-9-CM codes 564.5 and 787.91) within one year from the index date. Overall and CS-related healthcare resource utilization and costs were compared between patients with and without non-infectious diarrhea during the one year period after the index date. RESULTS: There were 2822 newly diagnosed CS patients; 534 (18.9%) had evidence of non-infectious diarrhea. Compared to patients without non infectious diarrhea, non-infectious diarrhea patients more commonly had at >= 1 CS-related hospitalization (13.7% vs 7.2%), >= 1 CS-related ED visit (11.0% vs 4.4%), and CS-related office visits in one year (6.9 vs 4.1; all P < 0.001). After adjusting for demographics, region, number of chronic conditions and the Charlson Comorbidity Index, the proportions of patients with any and with CS related hospitalizations were 9.7% and 6.8% higher, respectively, among non infectious diarrhea patients compared to those with without non-infectious diarrhea (P < 0.001). Unadjusted costs were significantly higher among non infectious diarrhea patients vs those without non-infectious diarrhea. The non infectious diarrhea group was also more costly, with adjusted mean annual costs of $81610, compared to $51719 in the group without non-infectious diarrhea (P < 0.001). CONCLUSION: Diarrhea is burdensome and costly in CS patients. Reduction of CS-related healthcare expenditures may be achievable through preventive treatment and appropriate management of diarrhea in CS. PMID- 26877617 TI - Role of a liver-first approach for synchronous colorectal liver metastases. AB - AIM: To evaluate the feasibility and survival outcomes of a liver-first approach. METHODS: Between January 2009 and April 2013, 18 synchronous colorectal liver metastases (sCRLMs) patients with a planned liver-first approach in the Hepatopancreatobiliary Surgery Department I of the Beijing Cancer Hospital were enrolled in this study. Clinical data, surgical outcomes, morbidity and mortality rates were collected. The feasibility and long-term outcomes of the approach were retrospectively analyzed. RESULTS: Sixteen patients (88.9%) completed the treatment protocol for primary and liver tumors. The main reason for treatment failure was liver disease recurrence. The 1 and 3 year overall survival rates were 94.4% and 44.8%, respectively. The median survival time was 30 mo. The postoperative morbidity and mortality were 22.2% and 0%, respectively, following a hepatic resection, and were 18.8% and 0%, respectively, after a colorectal surgery. CONCLUSION: The liver-first approach appeared to be feasible and safe. It can be performed with a comparable mortality and morbidity to the traditional treatment paradigm. This approach might offer a curative opportunity for sCRLM patients with a high liver disease burden. PMID- 26877618 TI - Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation. AB - AIM: To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT). METHODS: We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by chi(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression. RESULTS: Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 +/- 3.41 ng/mL vs 4.47 +/- 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (>= 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy. CONCLUSION: A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial. PMID- 26877620 TI - Pancreatitis in hand-foot-and-mouth disease caused by enterovirus 71. AB - Some viruses, including certain members of the enterovirus genus, have been reported to cause pancreatitis, especially Coxsackie virus. However, no case of human enterovirus 71 (EV71) associated with pancreatitis has been reported so far. We here report a case of EV71-induced hand-foot-and-mouth disease (HFMD) presenting with pancreatitis in a 2-year-old girl. This is the first report of a patient with acute pancreatitis in HFMD caused by EV71. We treated the patient conservatively with nasogastric suction, intravenous fluid and antivirals. The patient's symptoms improved after 8 d, and recovered without complications. We conclude that EV71 can cause acute pancreatitis in HFMD, which should be considered in differential diagnosis, especially in cases of idiopathic pancreatitis. PMID- 26877619 TI - Inferoposterior duodenal approach for laparoscopic pancreaticoduodenectomy. AB - AIM: To investigate the advantages of inferoposterior duodenal approach (IPDA) for laparoscopic pancreaticoduodenectomy (LPD). METHODS: A total of 36 patients subjected to LPD were admitted to the Affiliated Yijishan Hospital of Wannan Medical College from December 2009 to February 2015. These patients were diagnosed with an ampullary tumour or a pancreatic head tumour through computed tomography, magnetic resonance imaging or endoscopic retrograde cholangiopancreatography preoperatively. The cases were selected on the basis of the following criteria: tumour diameter < 4 cm; no signs of peripheral vascular invasion; evident lymph node swelling; and distant metastasis. Of the 36 cases, 20 were subjected to anterior approach (AA; AA group) and 16 were subjected to IPDA (IPDA group). Specimen removal time, intraoperative blood loss and postoperative complications in the two groups were observed, and their differences were compared. RESULTS: During the operation, 2 cases in the AA group and 2 cases in the IPDA group were converted to laparotomy; these cases were excluded from statistical analysis. The remaining 32 cases successfully completed the surgery. The AA group and IPDA group exhibited the specimen removal time of 205 +/- 52 and 160 +/- 35 min, respectively, and the difference was significant (P < 0.01). The AA group and IPDA group revealed the intraoperative blood loss of 360 +/- 210 mL and 310 +/- 180 mL, respectively, but these values were not significantly different. Postoperative pathological results revealed 4 cases of inferior common bile duct cancer, 8 cases of duodenal papillary cancer, 6 cases of ampullary cancer, 13 cases of pancreatic cancer, 3 cases of chronic pancreatitis accompanied with cyst formation or duct expansion, and 2 cases of mucinous cystic tumour in the pancreatic head. The postoperative complications were pulmonary Staphylococcus aureus infection, incision faulty union, ascites induced poor drainage accompanied with infection, bile leakage, pancreatic leakage and delayed abdominal bleeding. CONCLUSION: In IPDA, probing for important steps can be performed in early stages, surgical procedures can be optimised and operation time can be shortened. PMID- 26877621 TI - Acquired double pylorus: Clinical and endoscopic characteristics and four-year follow-up observations. AB - Double pylorus (DP), or duplication of the pylorus, is an uncommon condition that can be either congenital or acquired. Acquired DP (ADP) occurs when a peptic ulcer erodes and creates a fistula between the duodenal bulb and the distal stomach. The clinical features and endoscopic characteristics of four patients with ADP were reviewed and compared with previously reported cases. An accessory channel connects the lesser curvature of the prepyloric antrum with the duodenal bulb, and in all cases, a peptic ulcer was located in or immediately adjacent to the accessory channel. In one of the patients, the bridge between the double channel pylorus disappeared, resulting in a single large opening and duodenal kissing ulcer after two years and three months. Finally, nonsteroidal anti inflammatory drugs, Helicobacter pylori and other risk factors associated with ADP are assessed. PMID- 26877622 TI - Normative Feedback and Adolescent Readiness to Change: A Small Randomized Trial. AB - For adolescents with substance use problems, it is unknown whether the provision of normative feedback is a necessary active ingredient in motivational interviewing (MI). This study investigated the impact of normative feedback on adolescents' readiness to change and perceptions of MI quality. Adolescents referred for substance use disorder (SUD) assessments were randomized to MI with normative feedback (NF; MI + NF, n = 26) or MI only (MI, n = 22). There were no significant differences between the MI + NF or MI conditions with reference to changes in readiness, and although not significant, there was a decline in readiness for the overall sample. Treatment satisfaction and ratings of MI quality were generally high with no between-group differences. Post hoc analyses revealed a nonsignificant trend where race interacted with treatment condition. Larger replication studies are needed to further study the effects of NF and potential NF by participant characteristic interactions. PMID- 26877623 TI - Stakeholder Opinions And Ethical Perspectives Support Complete Disclosure Of Incidental Findings In MRI Research. AB - How far does a researcher's responsibility extend when an incidental finding is identified? Balancing pertinent ethical principles such as beneficence, respect for persons, and duty to rescue is not always straightforward, particularly in neuroimaging research where empirical data that might help guide decision-making is lacking. We conducted a systematic survey of perceptions and preferences of 396 investigators, research participants and IRB members at our institution. Using the partial entrustment model as described by Richardson, we argue that our data supports universal reading by a neuroradiologist of all research MRI scans for incidental findings and providing full disclosure to all participants. PMID- 26877624 TI - Are Approaches to Learning in Kindergarten Associated with Academic and Social Competence Similarly? PMID- 26877625 TI - Using Interactive Data Visualizations for Exploratory Analysis in Undergraduate Genomics Coursework: Field Study Findings and Guidelines. AB - Life scientists increasingly use visual analytics to explore large data sets and generate hypotheses. Undergraduate biology majors should be learning these same methods. Yet visual analytics is one of the most underdeveloped areas of undergraduate biology education. This study sought to determine the feasibility of undergraduate biology majors conducting exploratory analysis using the same interactive data visualizations as practicing scientists. We examined 22 upper level undergraduates in a genomics course as they engaged in a case-based inquiry with an interactive heat map. We qualitatively and quantitatively analyzed students' visual analytic behaviors, reasoning and outcomes to identify student performance patterns, commonly shared efficiencies and task completion. We analyzed students' successes and difficulties in applying knowledge and skills relevant to the visual analytics case and related gaps in knowledge and skill to associated tool designs. Findings show that undergraduate engagement in visual analytics is feasible and could be further strengthened through tool usability improvements. We identify these improvements. We speculate, as well, on instructional considerations that our findings suggested may also enhance visual analytics in case-based modules. PMID- 26877626 TI - Minimally Invasive Surgery in Pediatric Trauma: One Institution's 20-Year Experience. AB - BACKGROUND: Minimally invasive surgery (MIS) for trauma in pediatric cases remains controversial. Recent studies have shown the validity of using minimally invasive techniques to decrease the rate of negative and nontherapeutic laparotomy and thoracotomy. The purpose of this study was to evaluate the diagnostic accuracy and therapeutic options of MIS in pediatric trauma at a level I pediatric trauma center. METHODS: We reviewed cases of patients aged 15 years and younger who had undergone laparoscopy or thoracoscopy for trauma in our institution over the past 20 years. Each case was evaluated for mechanism of injury, computed tomographic (CT) scan findings, operative management, and patient outcomes. RESULTS: There were 23 patients in the study (16 boys and 7 girls). Twenty-one had undergone diagnostic laparoscopy and 2 had had diagnostic thoracoscopy. In 16, there were positive findings in diagnostic laparoscopy. Laparoscopic therapeutic interventions were performed in 6 patients; the remaining 10 required conversion to laparotomy. Both patients who underwent diagnostic thoracoscopy had positive findings. One had a thoracoscopic repair, and the other underwent conversion to thoracotomy. There were 5 negative diagnostic laparoscopies. There was no mortality among the 23 patients. CONCLUSIONS: The use of laparoscopy and thoracoscopy in pediatric trauma helps to reduce unnecessary laparotomy and thoracotomy. Some injuries can be repaired by a minimally invasive approach. When conversion is necessary, the use of these techniques can guide the placement and size of surgical incisions. The goal is to shift the paradigm in favor of using MIS in the treatment of pediatric trauma as the first-choice modality in stable patients. PMID- 26877627 TI - Laparoscopic Liver Resection for Tumors in the Left Lateral Liver Section. AB - BACKGROUND: The laparoscopic approach is increasingly adopted for liver resections today especially for lesions located in the left lateral liver section. This study was conducted to determine the impact of the introduction of laparoscopic liver resection (LLR) as a surgical option for suspected small- to medium-sized (<8 cm) tumors located in the left lateral section (LLS). METHODS: This is a retrospective review of 156 consecutive patients who underwent LLR or open liver resection (OLR) of tumors located in the LLS. The study was divided into 2 consecutive periods (period 1, January 2003 through September 2006, and period 2, October 2006 through April 2014); LLR was available as a surgical option only in the latter period. Comparisons made were LLR versus OLR, LLR versus OLR (in period 2 only), and resections performed in period 1 versus period 2. RESULTS: Forty-two patients underwent LLR with 4 conversions. LLR was significantly associated with a longer median operative time [167.5 minutes (range, 60-525) vs 105 minutes (range, 40-235); P < .001], decreased need for the Pringle maneuver [n = 1 (2%) vs 22 (19%); P = .008], and shorter postoperative stay [n = 4 (range, 1-10) days vs 5 days (range, 2-47); P < .001] compared with open resection. Comparison of the 42 patients who underwent LLR with the 64 contemporaneous patients who underwent OLR demonstrated similar outcomes. Again, LLR was associated with a significantly longer operation, decreased need for the Pringle maneuver, and shorter hospital stay. CONCLUSIONS: LLR can be safely adopted to treat lesions in the LLS. The procedure is associated with a shorter postoperative stay and a decreased need for the Pringle maneuver, but longer operative time compared with that required for OLR. PMID- 26877628 TI - Intrinsic spin torque without spin-orbit coupling. AB - We derive an intrinsic contribution to the non-adiabatic spin torque for non uniform magnetic textures. It differs from previously considered contributions in several ways and can be the dominant contribution in some models. It does not depend on the change in occupation of the electron states due to the current flow but rather is due to the perturbation of the electronic states when an electric field is applied. Therefore it should be viewed as electric-field-induced rather than current-induced. Unlike previously reported non-adiabatic spin torques, it does not originate from extrinsic relaxation mechanisms nor spin-orbit coupling. This intrinsic non-adiabatic spin torque is related by a chiral connection to the intrinsic spin-orbit torque that has been calculated from the Berry phase for Rashba systems. PMID- 26877629 TI - A Systematic Review and Meta-Analysis of the Utility of Corticosteroids in the Treatment of Hyperemesis Gravidarum. AB - BACKGROUND: Corticosteroids (CCS) are effective in reducing chemotherapy-induced nausea and vomiting, but it is unknown whether CCS are effective in treating hyperemesis gravidarum (HG). METHODS: We searched PubMed and ClinicalTrials.gov from inception to May 15, 2015, for randomized controlled trials examining the effects of CCS in HG. RESULTS: We identified five trials (n = 310) examining the effects of CCS in women with HG. Meta-analysis was possible for one outcome (n = 214) and showed no significant effect of CCS on readmission rates (odds ratio, 0.37; 95% confidence internal: 0.1-1.35). Two small studies (n = 104) reported a reduction of vomiting episodes, and one (n = 24) found improvement of well-being, but no effect on other outcomes. None of the studies that investigated perinatal outcome (n = 173) found an effect of CCS and were underpowered to investigate teratogenic effects. We found evidence of publication bias. CONCLUSION: Meta analysis yielded no effect of CCS therapy on readmission rates. Single small studies indicated possible beneficial effects on other outcomes. Future high quality trials are necessary and would benefit from consensus on HG definition and core outcomes of HG therapy. PMID- 26877630 TI - Effects of Beak Trimming, Stocking Density and Sex on Carcass Yield, Carcass Components, Plasma Glucose and Triglyceride Levels in Large White Turkeys. AB - This study was conducted to determine the effects of beak trimming, stocking density (D) and sex (S) on live weight (LW), carcass yield and its component, and plasma glucose (PG) and triglyceride levels in Large White turkeys. To accomplish this aims, totally 288 d old large white turkey chicks (144 in each sex) were used. Beaks of 77 male and female poults were trimmed when 8 d old with an electrical beak trimmer. The birds were fed by commercial turkey rasion. Experiment was designed as 2 * 2 * 2 factorial arrangement with 3 replications in each group. Beak trimming and stocking density did not affect live weight, carcass composition and its components. The higher LW and carcass weight observed in trimmed groups. As expected, male birds are heavier than female, and carcass percentage (CP) would be adverse. However, in this study, CP of male was higher in trimmed, in 0.25 m(2)/bird. (D) * sex (S) interaction had an effect on both CP and thigh weights (p<0.05). Significantly D * S was observed in LW, CP and PG. The weight of carcass and its some components were higher in male. S * D interaction had an effect on plasma glucose level (p<0.05). Triglyceride level was affected (p<0.05) by sex. Significant relationships were found between percentage of thighs (r=0.447, p<0.01) and percentage of breast (r=0.400, p<0.01). According to this study, it can be said that trimming is useful with density of 0.25 m(2)/bird in turkey fattening. PMID- 26877631 TI - Effect of Ginger Extract and Citric Acid on the Tenderness of Duck Breast Muscles. AB - The objective of this study was to examine the effect of ginger extract (GE) combined with citric acid on the tenderness of duck breast muscles. Total six marinades were prepared with the combination of citric acid (0 and 0.3 M citric acid) and GE (0, 15, and 30%). Each marinade was sprayed on the surface of duck breasts (15 mL/100 g), and the samples were marinated for 72 h at 4C. The pH and proteolytic activity of marinades were determined. After 72 h of marination, Warner Bratzler shear force (WBSF), myofibrillar fragmentation index (MFI), pH, cooking loss, moisture content, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and protein solubility were evaluated. There was no significant (p>0.05) difference in moisture content or cooking loss among all samples. However, GE marination resulted in a significant (p<0.05) decrease in WBSF but a significant (p<0.05) increase in pH and MFI. In addition, total protein and myofibrillar protein solubility of GE-marinated duck breast muscles in both WOC (without citric acid) and WC (with citric acid) conditions were significantly (p<0.05) increased compared to non-GE-marinated duck breast muscles. SDS-PAGE showed an increase of protein degradation (MHC and actin) in WC condition compared to WOC condition. There was a marked actin reduction in GE treated samples in WC. The tenderization effect of GE combined with citric acid may be attributed to various mechanisms such as increased MFI and myofibrillar protein solubility. PMID- 26877632 TI - Meat Quality of Loin and Top Round Muscles from the Hanwoo and Holstein Veal Calves. AB - This study was conducted to compare the meat qualities of loin (m. longissimus dorsi) and top round (m. semimembranosus) from Hanwoo and Holstein veal. Ten Hanwoo and Holstein calves were randomly selected from a local cattle farm and raised. They were slaughtered when they were 8 mon old and weighed. Weight and percentage in primal cuts and slaughter performance of Hanwoo and Holstein veal calves are obtained. Immediately after weighting, slices of loin and top round muscles were sampled. After vacuum packaging, the samples were subjected to proximate composition, physicochemical and microbiological analyses. Dressing weight and percentage were heavier and greater (p<0.05) in the Holstein than in the Hanwoo. Water contents of the top round muscle was higher in the Holstein than in the Hanwoo (p<0.05). Water-holding capacity, protein content and CIE L* (lightness) of both muscles were higher in the Holstein than in the Hanwoo veal, whereas fat content, pH, cooking loss, a* (redness), and b* (yellowness) were higher in the Hanwoo than in the Holstein veal (p<0.05). Thiobarbituric acid and volatile basic nitrogen values of both the muscles were lower in the Hanwoo than in the Holstein veal during the first 10 d of storage (p<0.05). PMID- 26877633 TI - Identification of Antihypertensive Peptides Derived from Low Molecular Weight Casein Hydrolysates Generated during Fermentation by Bifidobacterium longum KACC 91563. AB - Angiotensin-converting enzyme (ACE) inhibitory activity was evaluated for the low molecular-weight fraction (<3 kDa) obtained from milk fermentation by Bifidobacterium longum KACC91563. The ACE inhibitory activity in this fraction was 62.3%. The peptides generated from the <3 kDa fraction were identified by liquid chromatography-electrospray ionization quantitative time-of-flight mass spectrometry analysis. Of the 28 peptides identified, 11 and 16 were identified as beta-casein (CN) and alphas1-CN, respectively. One peptide was identified as kappa-CN. Three peptides, YQEPVLGPVRGPFPIIV, QEPVLGPVRGPFPIIV, and GPVRGPFPIIV, from beta-CN corresponded to known antihypertensive peptides. We also found 15 peptides that were identified as potential antihypertensive peptides because they included a known antihypertensive peptide fragment. These peptides were as follows: RELEELNVPGEIVE (f1-14), YQEPVLGPVRGPFP (f193-206), EPVLGPVRGPFPIIV (f195 206), PVLGPVRGPFPIIV (f196-206), VLGPVRGPFPIIV (f197-206), and LGPVRGPFPIIV (f198 206) for beta-CN; and APSFSDIPNPIGSENSEKTTMPLW (f176-199), SFSDIPNPIGSENSEKT- TMPLW (f178-199), FSDIPNPIGSENSEKTTMPLW (f179-199), SDIPNPIGSENSEKTTMPLW (f180 199), DIPNPIGSENSEKTTMPLW (f181-199), IPNPIGSENSEKTTMPLW (f182-199), PIGSENSEKTTMPLW (f185-199), IGSENSEKTTMPLW (f186-199), and SENSEKTTMPLW (f188 199) for alphas1-CN. From these results, B. longum could be used as a starter culture in combination with other lactic acid bacteria in the dairy industry, and/or these peptides could be used in functional food manufacturing as additives for the development of a product with beneficial effects for human health. PMID- 26877634 TI - Effects of Edible Seaweed on Physicochemical and Sensory Characteristics of Reduced-salt Frankfurters. AB - The effects of sea tangle, sea mustard, hijiki, and glasswort were investigated based on the proximate composition, salinity, cooking loss, emulsion stability, pH, color, texture profile analysis, apparent viscosity, and sensory characteristics of reduced-salt (NaCl) meat batter and frankfurters. The moisture content, salinity, lightness of the meat batter and frankfurter, hardness, gumminess, and chewiness of the reduced-salt frankfurters with sea weeds were lower than the control without seaweed (p<0.05). The protein content, springiness, and cohesiveness of the reduced-salt frankfurters were not significantly different among the treatments (p>0.05). The moisture content, salinity, cooking loss, lightness, redness, hardness, gumminess, and chewiness of treatments with sea tangle and with sea mustard were lower than the control (p<0.05). Among the sensory traits, color was highest in the control (p<0.05). The flavor was also highest in the control. The treatments with sea tangle and with sea mustard samples had high tenderness, juiciness, and overall acceptability scores similar to the control (p<0.05). The results of this study show that the combination of low-salt and seaweed in the formulation successfully improved reduced-salt frankfurters, improving sensory characteristics to levels similar to the regular salt control (1.5%). PMID- 26877635 TI - Changes in Meat Quality Characteristics of the Sous-vide Cooked Chicken Breast during Refrigerated Storage. AB - This study was performed to investigate the changes in meat quality characteristics of the sous vide cooked chicken breast during refrigerated storage at 4C for 14 d between before and after sous-vide cooking. Cooking loss and shear force were significantly increased, whereas expressible drip was significantly decreased along with reduction in the water holding capacity in both of two groups. Redness of meat juice was significantly (p<0.05) increased during storage, and considerably increased in the refrigerated samples after sous vide cooked at the 7 to 10 d. The thiobarbituric acid reactive substances (TBARS) was significantly increased and was higher in the refrigerator stored chicken breast samples after sous-vide cooking. The volatile basic nitrogen (VBN) value was significantly increased in both groups, but the VBN value of the stored raw meat sample before sous-vide cooking was increased at an early storage, while the VBN value of the stored sample after sous-vide cooking was increased gradually in this study. Total viable counts and coliform counts were significantly decreased during storage, and coliforms were not detected after 7 d of storage in both groups. Salmonella spp. was not detected during the whole studied period. The outcome of this research can provide preliminary data that could be used to apply for further study of chicken breast using sous-vide cooking method that could be attractive to consumers. PMID- 26877636 TI - Analytical Determination of Vitamin B12 Content in Infant and Toddler Milk Formulas by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS). AB - The development of a sample preparation method and optimization of the analytical instrumentation conditions were performed for the determination of the vitamin B12 content in emulsified baby foods sold on the Korea market. After removal of the milk protein and fats by chloroform extraction and centrifugation, the vitamin B12 was water extracted from the sample. Following filtration of the solution through a nylon filter, the water-soluble extract was purified by solid phase extraction using a Liquid Chromatography Tandem Mass Spectrometry (LC MS/MS). The solution eluted from the cartridge was dried under a stream of nitrogen gas and reconstituted with 1 mL of water. The sample solution was injected into an LC-MS/MS system after optimizing the mobile phase for vitamin B12 detection. The calibration curve showed good linearity with the coefficient of correlation (r (2)) value of 0.9999. The limit of detection was 0.03 ug/L and the limit of quantitation was 0.1 ug/L. The method of detection limit was 0.02 ug/kg. The vitamin B12 recovery from a spiking test was 99.62% for infant formula and 99.46% for cereal-based baby food. The sample preparation method developed in this study would be appropriate for the rapid determination of the vitamin B12 content in infant formula and baby foods with emulsified milk characteristics. The ability to obtain stable results more quickly and efficiently would also allow governments to exercise a more extensive quality control inspection and monitoring of products expected to contain vitamin B12. This method could be implemented in laboratories that require time and labor saving. PMID- 26877637 TI - Evaluation of Physicochemical Deterioration and Lipid Oxidation of Beef Muscle Affected by Freeze-thaw Cycles. AB - This study was performed to explore the deterioration of physicochemical quality of beef hind limb during frozen storage at -20C, affected by repeated freeze-thaw cycles. The effects of three successive freeze-thaw cycles on beef hind limb were investigated comparing with unfrozen beef muscle for 80 d by keeping at -20+/-1C. The freeze-thaw cycles were subjected to three thawing methods and carried out to select the best one on the basis of deterioration of physicochemical properties of beef. As the number of repeated freeze-thaw cycles increased, drip loss decreased and water holding capacity (WHC) increased (p<0.05) till two cycles and then decreased. Cooking loss increased in cycle one and three but decreased in cycle two. Moreover, drip loss, WHC and cooking loss affected (p<0.05) by thawing methods within the cycles. However, pH value decreased (p<0.05), but peroxide value (p<0.05), free fatty acids value (p<0.05) and TBARS value increased (p<0.05) significantly as the number of repeated freeze-thaw cycles increased. Moreover, significant (p<0.05) interactive effects were found among the thawing methods and repeated cycles. As a result, freeze-thaw cycles affected the physicochemical quality of beef muscle, causing the degradation of its quality. PMID- 26877638 TI - Effects of Glasswort (Salicornia herbacea L.) Hydrates on Quality Characteristics of Reduced-salt, Reduced-fat Frankfurters. AB - This study evaluated the effects of adding glasswort hydrate containing non-meat ingredient (GM, carboxy methyl cellulose; GC, carrageenan; GI, isolated soy protein; GS, sodium caseinate) on the quality characteristics of reduced-salt, reduced-fat frankfurters. The pH and color evaluation showed significant differences, depending on the type of glasswort hydrate added (p<0.05). In the raw batters and cooked frankfurters, the addition of glasswort hydrate decreased the redness and increased the yellowness in comparison with frankfurters without glasswort hydrate. The reduction in salt and fat content significantly increased cooking loss and decreased hardness, tenderness and juiciness (p<0.05). Glasswort hydrate containing non-meat ingredient improved cooking loss, water holding capacity, emulsion stability, hardness, and viscosity of reduced-salt, reduced fat frankfurters. The GM treatment had the highest myofibiliar protein solubility among all treatments, which was associated with emulsion stability and viscosity. The GC treatment had higher values for all texture parameters than the control. In the sensory evaluation, the addition of glasswort hydrate with non-meat ingredient improved tenderness and juiciness of reduced-salt, reduced-fat frankfurters. GM, GC, and GI treatments improved not only the physicochemical properties but also the sensory characteristics of reduced-salt, reduced-fat frankfurters. The results indicated that the use of glasswort hydrate containing non-meat ingredient was improved the quality characteristics of reduced-salt, reduced-fat frankfurters. PMID- 26877639 TI - Effect of Frozen Storage Temperature on the Quality of Premium Ice Cream. AB - The market sales of premium ice cream have paralleled the growth in consumer desire for rich flavor and taste. Storage temperature is a major consideration in preserving the quality attributes of premium ice cream products for both the manufacturer and retailers during prolonged storage. We investigated the effect of storage temperature (-18C, -30C, -50C, and -70C) and storage times, up to 52 wk, on the quality attributes of premium ice cream. Quality attributes tested included ice crystal size, air cell size, melting resistance, and color. Ice crystal size increased from 40.3 MUm to 100.1 MUm after 52 wk of storage at -18C. When ice cream samples were stored at -50C or -70C, ice crystal size slightly increased from 40.3 MUm to 57-58 MUm. Initial air cell size increased from 37.1 MUm to 87.7 MUm after storage at -18C for 52 wk. However, for storage temperatures of -50C and -70C, air cell size increased only slightly from 37.1 MUm to 46-47 MUm. Low storage temperature (-50C and -70C) resulted in better melt resistance and minimized color changes in comparison to high temperature storage (-18C and -30C). In our study, quality changes in premium ice cream were gradually minimized according to decrease in storage temperature up to-50C. No significant beneficial effect of -70C storage was found in quality attributes. In the scope of our experiment, we recommend a storage temperature of -50C to preserve the quality attributes of premium ice cream. PMID- 26877640 TI - Inactivation of Escherichia coli, Saccharomyces cerevisiae, and Lactobacillus brevis in Low-fat Milk by Pulsed Electric Field Treatment: A Pilot-scale Study. AB - We investigated the effects of a pulsed electric field (PEF) treatment on microbial inactivation and the physical properties of low-fat milk. Milk inoculated with Escherichia coli, Saccharomyces cerevisiae, or Lactobacillus brevis was supplied to a pilot-scale PEF treatment system at a flow rate of 30 L/h. Pulses with an electric field strength of 10 kV/cm and a pulse width of 30 MUs were applied to the milk with total pulse energies of 50-250 kJ/L achieved by varying the pulse frequency. The inactivation curves of the test microorganisms were biphasic with an initial lag phase (or shoulder) followed by a phase of rapid inactivation. PEF treatments with a total pulse energy of 200 kJ/L resulted in a 4.5-log reduction in E. coli, a 4.4-log reduction in L. brevis, and a 6.0 log reduction in S. cerevisiae. Total pulse energies of 200 and 250 kJ/L resulted in greater than 5-log reductions in microbial counts in stored PEF-treated milk, and the growth of surviving microorganisms was slow during storage for 15 d at 4C. PEF treatment did not change milk physical properties such as pH, color, or particle-size distribution (p<0.05). These results indicate that a relatively low electric-field strength of 10 kV/cm can be used to pasteurize low-fat milk. PMID- 26877641 TI - Effects of Freeze-dried Mulberry on Antioxidant Activities and Fermented Characteristics of Yogurt during Refrigerated Storage. AB - This study investigated the effect of added freeze-dried mulberry fruit juice (FDMJ) (1, 3 and 5%) on the antioxidant activity and fermented characteristic of yogurt during refrigerated storage. A decrease in pH of yogurt and increase in acidity was observed during fermentation. The yogurts with FDMJ exhibited faster rate of pH reduction than control. Initial lactic acid bacteria count of yogurt was 6.49-6.94 Log CFU/g and increased above 9 Log CFU/g in control and 1% in FDMJ yogurt for 24 h. The total polyphenol and anthocyanin content of FDMJ yogurt was higher than that of control due to the presence of phytochemical contents in mulberry. Moreover, antioxidant activity such as DPPH and reducing power was highest 5% FDMJ yogurt. During cold storage, pH decreased or remained constant in all yogurts with values ranging from 4.08 to 4.78 units. In sensory evaluation, the score of 1% FDMJ yogurt was ranked higher when compared with other yogurts. It is proposed that mulberry fruit juice powder can be used to improve sensory evaluation and enhance functionality of yogurt. PMID- 26877642 TI - Probabilistic Models to Predict Listeria monocytogenes Growth at Low Concentrations of NaNO2 and NaCl in Frankfurters. AB - This study developed probabilistic models to describe Listeria monocytogenes growth responses in meat products with low concentrations of NaNO2 and NaCl. A five-strain mixture of L. monocytogenes was inoculated in NBYE (nutrient broth plus 0.6% yeast extract) supplemented with NaNO2 (0-141 ppm) and NaCl (0-1.75%). The inoculated samples were then stored under aerobic and anaerobic conditions at 4, 7, 10, 12, and 15C for up to 60 d. Growth response data [growth (1) or no growth (0)] for each combination were determined by turbidity. The growth response data were analyzed using logistic regression to predict the growth probability of L. monocytogenes as a function of NaNO2 and NaCl. The model performance was validated with the observed growth responses. The effect of an obvious NaNO2 and NaCl combination was not observed under aerobic storage condition, but the antimicrobial effect of NaNO2 on the inhibition of L. monocytogenes growth generally increased as NaCl concentration increased under anaerobic condition, especially at 7-10C. A single application of NaNO2 or NaCl significantly (p<0.05) inhibited L. monocytogenes growth at 4-15C, but the combination of NaNO2 or NaCl more effectively (p<0.05) inhibited L. monocytogenes growth than single application of either compound under anaerobic condition. Validation results showed 92% agreement between predicted and observed growth response data. These results indicate that the developed model is useful in predicting L. monocytogenes growth response at low concentrations of NaNO2 and NaCl, and the antilisterial effect of NaNO2 increased by NaCl under anaerobic condition. PMID- 26877643 TI - Effect of Dietary Processed Sulfur Supplementation on Water-holding Capacity, Color, and Lipid Profiles of Pork. AB - This study was performed to investigate the effect of dietary processed sulfur supplementation on water-holding capacity, color, and lipid profiles of pork according to the level of dietary processed sulfur (0%, CON; 0.3%, S). The pigs were slaughtered at an average final weight of 120 kg, and the longissimus dorsi muscles were collected from the carcasses. As results, pork processed with sulfur had significantly higher moisture and ash contents compared to those of CON but lower crude fat, pH, expressible drip, lower redness and yellowness, and greater lightness. Pork processed with sulfur showed significantly lower total lipid content, triglycerides, and atherosclerosis index but significantly higher high density lipoprotein cholesterol. Feeding processed sulfur significantly lowered myristic acid, heptadecanoic acid, and stearic acid contents, whereas monounsaturated fatty acids and oleic acids were significantly higher compared to those in the CON. Higher amounts of polyunsaturated fatty acids and n-6 fatty acids were observed in the pork processed with sulfur than that of the CON. Therefore, supplementing pigs with dietary sulfur improved nutrient and meat quality. PMID- 26877644 TI - Bioactive Peptides in Milk and Dairy Products: A Review. AB - Functionally and physiologically active peptides are produced from several food proteins during gastrointestinal digestion and fermentation of food materials with lactic acid bacteria. Once bioactive peptides (BPs) are liberated, they exhibit a wide variety of physiological functions in the human body such as gastrointestinal, cardiovascular, immune, endocrine, and nervous systems. These functionalities of the peptides in human health and physiology include antihypertensive, antimicrobial, antioxidative, antithrombotic, opioid, anti appetizing, immunomodulatory and mineral-binding activities. Most of the bioactivities of milk proteins are latent, being absent or incomplete in the original native protein, but full activities are manifested upon proteolytic digestion to release and activate encrypted bioactive peptides from the original protein. Bioactive peptides have been identified within the amino acid sequences of native milk proteins. Due to their physiological and physico-chemical versatility, milk peptides are regarded as greatly important components for health promoting foods or pharmaceutical applications. Milk and colostrum of bovine and other dairy species are considered as the most important source of natural bioactive components. Over the past a few decades, major advances and developments have been achieved on the science, technology and commercial applications of bioactive components which are present naturally in the milk. Although the majority of published works are associated with the search of bioactive peptides in bovine milk samples, some of them are involved in the investigation of ovine or caprine milk. The advent of functional foods has been facilitated by increasing scientific knowledge about the metabolic and genomic effects of diet and specific dietary components on human health. PMID- 26877645 TI - Evaluation of Porcine Myofibrillar Protein Gel Functionality as Affected by Microbial Transglutaminase and Red Bean [Vignia angularis] Protein Isolate at Various pH Values. AB - This study was investigated to determine the effect of microbial transglutaminase (MTG) with or without red bean protein isolate (RBPI) on the porcine myofibrillar protein (MP) gel functionality at different pH values (pH 5.75-6.5). Cooking yield (CY, %), gel strength (GS, gf), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were determined to measure gel characteristics. Since no differences were observed the interaction between 1% RBPI and pH, data were pooled. CY increased with the addition of 1% RBPI, while it was not affected by pH values. GS increased with increased pH and increased when 1% RBPI was added, regardless of pH. There were distinctive endothermic protein peaks, at 56.55 and 75.02C at pH 5.75, and 56.47 and 72.43C at pH 6.5 in DSC results, which revealed decreased temperature of the first peak with the addition of 1% RBPI and increased pH. In SEM, a more compact structure with fewer voids was shown with the addition of 1% RBPI and increased pH from 5.75 to 6.5. In addition, the three-dimensional structure was highly dense and hard at pH 6.5 when RBPI was added. These results indicated that the addition of 1% RBPI at pH 6.5 in MTG-mediated MP represent the optimum condition to attain maximum gel formation and protein gel functionality. PMID- 26877646 TI - Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide. AB - The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic beta-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and beta-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic beta-cells. PMID- 26877647 TI - Chemical Components and Meat Quality Traits Related to Palatability of Ten Primal Cuts from Hanwoo Carcasses. AB - To determine chemical components and meat quality traits related to palatability of 10 primal cuts, 25 Hanwoo carcasses were selected from 5 carcasses * 5 quality grades and used to obtain proximate data and meat quality characteristics. Significant differences (p<0.05) in chemical component and meat quality were found among the 10 primal cuts. The highest fat content was found in the kalbi, followed by dungsim, yangjee, chaekeut, ansim, abdari, suldo, moksim, udun, and satae. Protein and moisture contents in the 10 primal cuts were in reverse order of fat content. Moksim had the highest drip loss % and cooking loss % than all other primal cuts while kalbi showed the lowest (p<0.05) percentage of drip and cooking loss. Ansim had the longest sarcomere length but the lowest shear force values than all other cuts (p<0.05). The highest (p<0.05) score for overall acceptability was observed in ansim. Moksim, udun, abdari, and satae were rated the lowest (p<0.05) in overall acceptability among the 10 primal cuts from Hanwoo carcasses. In conclusion, ansim, dungsim, chaekeut, and kalbi had the highest overall acceptability due to their higher fat contents and lower shear force values. PMID- 26877648 TI - Construction of a Recombinant Leuconostoc mesenteroides CJNU 0147 Producing 1,4 Dihydroxy-2-Naphthoic Acid, a Bifidogenic Growth Factor. AB - 1,4-Dihydroxy-2-naphthoic acid (DHNA), a precursor of menaquinone (vitamin K2), has an effect on growth stimulation of bifidobacteria and prevention of osteoporosis, making it a promising functional food material. Therefore, we tried to clone the menB gene encoding DHNA synthase from Leuconostoc mesenteroides CJNU 0147. Based on the genome sequence of Leu. mesenteroides ATCC 8293 (GenBank accession no., CP000414), a primer set (Leu_menBfull_F and Leu_menBfull_R) was designed for the PCR amplification of menB gene of CJNU 0147. A DNA fragment (1,190 bp), including the menB gene, was amplified, cloned into pGEM-T Easy vector, and sequenced. The deduced amino acid sequence of MenB (DHNA synthase) protein of CJNU 0147 had a 98% similarity to the corresponding protein of ATCC 8293. The menB gene was subcloned into pCW4, a lactic acid bacteria - E. coli shuttle vector, and transferred to CJNU 0147. The transcription of menB gene of CJNU 0147 (pCW4::menB) was increased, when compared with those of CJNU 0147 (pCW4) and CJNU 0147 (-). The DHNA was produced from it at a detectable level, indicating that the cloned menB gene of CJNU 0147 encoded a DHNA synthase which is responsible for the production of DHNA, resulting in an increase of bifidogenic growth stimulation activity. PMID- 26877649 TI - Anchoring Biodiversity Information: From Sherborn to the 21(st) century and beyond. PMID- 26877650 TI - Charles Davies Sherborn and the "Indexer's Club". AB - The first few words of the title of this symposium are "Anchoring Biodiversity Information". In order to properly anchor anything for a long-lasting future, a solid foundation needs to have been laid. For the zoological portion of biodiversity information, that firm foundation is best exemplified in the works of Charles Davies Sherborn. This man, like others of his ilk, was intimately focused on indexing names. This incredible focus was a life-long passion for him and culminated in his 9500-page Index Animalium of over 400,000 names of animals. This Index represents not only one of the most prodigious efforts in publication by a single man and the single most important reference to names in zoology, but a permanent legacy to the efforts of an indexer that proved to be an inspiration to many. PMID- 26877651 TI - A magpie with a card-index mind - Charles Davies Sherborn 1861-1942. AB - Charles Davies Sherborn was geologist, indexer and bibliographer extraordinaire. He was fascinated by science from an early age and like so many Victorians, the young Sherborn was a passionate natural history collector and was obsessed with expanding his collection of land and freshwater shells. He later described himself as being a 'thorough magpie' and having 'a card-index mind', and these two traits coalesced in his monumental Index Animalium, the compilation of which occupied 43 years of his life. One of the first visitors through the doors of the Natural History Museum in South Kensington when it opened in 1881, Sherborn began work there seven years later as one of the small band of unofficial scientific workers, paid by the number of fossils he prepared. By the time of his death in 1942, Sherborn's corner in the Museum was the first port of call for generations of scientists seeking advice, information - or an invitation to one of his famous 'smoke and chat' parties. In addition to his work on the Index, Sherborn is also responsible for rescuing from damp and probable destruction the huge archive of Sir Richard Owen, the great comparative anatomist and the prime mover behind the creation of the Natural History Museum, London. Without Sherborn, this invaluable resource of correspondence, manuscripts and books may well have been irretrievably ruined. PMID- 26877652 TI - Naming and Necessity: Sherborn's Context in the 19(th) Century. AB - By the late 19(th) Century, storms plaguing early Victorian systematics and nomenclature seemed to have abated. Vociferous disputes over radical renaming, the world-shaking clash of all-encompassing procrustean systems, struggles over centres of authority, and the issues of language and meaning had now been settled by the institution of a stable imperial museum and its catalogues, a set of rules for the naming of zoological objects, and a new professional class of zoologists. Yet, for all that tranquillity, the disputes simmered below the surface, re emerging as bitter struggles over synonyms, trinomials, the subspecies category, the looming issues of the philosophy of scientific language, and the aggressive new American style of field biology - all pressed in upon the received practice of naming and classifying organisms and the threat of anarchy. In the midst rose an index. This paper will explore the context of CD Sherborn's Index Animalium and those looming problems and issues which a laborious and comprehensive "index of nature" was meant to solve. PMID- 26877653 TI - Sherborn's foraminiferal studies and their influence on the collections at the Natural History Museum, London. AB - Sherborn's work on the Foraminifera clearly provided the initial spark to compile the major indexes for which he is famous. Contact and help from famous early micropalaeontologists such as T. Rupert Jones and Fortescue William Millett led Sherborn to produce his Bibliography of Foraminifera and subsequently a two-part Index of Foraminiferal Genera and Species. Edward Heron-Allen, whose mentor was Millett, was subsequently inspired by the bibliography to attempt to acquire every publication listed. This remarkable collection of literature was donated to the British Museum (Natural History) in 1926 along with the foraminiferal collections Heron-Allen had mainly purchased from early micropalaeontologists. This donation forms the backbone of the current NHM micropalaeontological collections. The NHM collections contain a relatively small amount of foraminiferal material published by Sherborn from the London Clay, Kimmeridge Clay and Speeton Clay. Another smaller collection reflects his longer-term interest in the British Chalk following regular fieldwork with A. W. Rowe. Other collections relating to Sherborn's early published work, particularly with T. R. Jones, are not present in the collections but these collections may have been sold or deposited elsewhere by his co-workers. PMID- 26877654 TI - 'Where is the damned collection?' Charles Davies Sherborn's listing of named natural science collections and its successors. AB - C. D. Sherborn published in 1940, under the imprint of Cambridge University Press but at his own expense, Where is the - Collection? This idiosyncratic listing of named natural science collections, and their fates, was useful, but incomplete, and uneven in its accuracy. It is argued that those defects were inevitable, given Sherborn's age and wartime conditions, and that what might seem one of Sherborn's less impressive works was in fact a pioneering work highly influential in stimulating the production of successor works now much used in curation, and in systematic and descriptive biology and palaeontology. The book also contributed to the development of collections research in the natural sciences, and the history of collections and of museums. PMID- 26877655 TI - Reinforcing the foundations of ornithological nomenclature: Filling the gaps in Sherborn's and Richmond's historical legacy of bibliographic exploration. AB - Due to its public popularity, ornithology has a huge corpus of scientific publication for a relatively small number of species. Although there are global checklists of currently recognised taxa, there has been only limited, mainly individual, effort to build a nomenclatural database that the science of ornithology deserves. This is especially true in relation to concise synonymies. With the arrival of ZooBank and the Biodiversity Heritage Library, the time has come to develop synonymies and to add fuller bibliographic detail to databases. The preparation for both began at the start of the 20(th) century with extensive work by Sherborn and Richmond. I discuss their legacy, offer notes on significant work since then, and provide suggestions for what remains to be done. To make solid the foundations for ornithological nomenclature and taxonomy, especially for synonymies, ornithologists will need to collaborate much more and contribute to the digital infrastructure. PMID- 26877656 TI - Sherborn's influence on Systema Dipterorum. AB - Flies make up more than 10% of the planetary biota and our well-being depends on how we manage our coexistence with flies. Storing and accessing relevant knowledge about flies is intimately connected with using correct names, and Systema Dipterorum provides a single authoritative classification for flies developed by consensus among contributors. The 160,000 species of flies currently known are distributed among 160 recent families and some 12,000 genera, which with their synonyms encompass a total of more than a quarter of a million names. These names and their associated classification are shared with relevant global solutions. Sherborn appears to have done remarkably well indexing Diptera names with an overall error rate estimated to be close to 1%. PMID- 26877657 TI - Unlocking Index Animalium: From paper slips to bytes and bits. AB - In 1996 Smithsonian Libraries (SIL) embarked on the digitization of its collections. By 1999, a full-scale digitization center was in place and rare volumes from the natural history collections, often of high illustrative value, were the focus for the first years of the program. The resulting beautiful books made available for online display were successful to a certain extent, but it soon became clear that the data locked within the texts needed to be converted to more usable and re-purposable form via digitization methods that went beyond simple page imaging and included text conversion elements. Library staff met with researchers from the taxonomic community to understand their path to the literature and identified tools (indexes and bibliographies) used to connect to the library holdings. The traditional library metadata describing the titles, which made them easily retrievable from the shelves of libraries, was not meeting the needs of the researcher looking for more detailed and granular data within the texts. The result was to identify proper print tools that could potential assist researchers in digital form. This paper outlines the project undertaken to convert Charles Davies Sherborn's Index Animalium into a tool to connect researchers to the library holdings: from a print index to a database to eventually a dataset. Sherborn's microcitation of a species name and his bibliographies help bridge the gap between taxonomist and literature holdings of libraries. In 2004, SIL received funding from the Smithsonian's Atherton Seidell Endowment to create an online version of Sherborn's Index Animalium. The initial project was to digitize the page images and re-key the data into a simple data structure. As the project evolved, a more complex database was developed which enabled quality field searching to retrieve species names and to search the bibliography. Problems with inconsistent abbreviations and styling of his bibliographies made the parsing of the data difficult. Coinciding with the development of the Biodiversity Heritage Library (BHL) in 2005, it became obvious there was a need to integrate the database converted Index Animalium, BHL's scanned taxonomic literature, and taxonomic intelligence (the algorithmic identification of binomial, Latinate name-strings). The challenges of working with legacy taxonomic citation, computer matching algorithms, and making connections have brought us to today's goal of making Sherborn available and linked to other datasets. Partnering with others to allow machine-to-machine communications the data is being examined for possible transformation into RDF markup and meeting the standards of Linked Open Data. SIL staff have partnered with Thomson Reuters and the Global Names Initiative to further enhance the Index Animalium data set. Thomson Reuters' staff is now working on integrating the species microcitation and species name in the ION: Index to Organism Names project; Richard Pyle (The Bishop Museum) is also working on further parsing of the text. The Index Animalium collaborative project's ultimate goal is to successful have researchers go seamlessly from the species name in either ION or the scanned pages of Index Animalium to the digitized original description in BHL - connecting taxonomic researchers to original authored species descriptions with just a click. PMID- 26877658 TI - Sherborn's Index Animalium: New names, systematic errors and availability of names in the light of modern nomenclature. AB - This study is aimed to shed light on the reliability of Sherborn's Index Animalium in terms of modern usage. The AnimalBase project spent several years' worth of teamwork dedicated to extracting new names from original sources in the period ranging from 1757 to the mid-1790s. This allowed us to closely analyse Sherborn's work and verify the completeness and correctness of his record. We found the reliability of Sherborn's resource generally very high, but in some special situations the reliability was reduced due to systematic errors or incompleteness in source material. Index Animalium is commonly used by taxonomists today who rely strongly on Sherborn's record; our study is directed most pointedly at those users. We recommend paying special attention to the situations where we found that Sherborn's data should be read with caution. In addition to some categories of systematic errors and mistakes that were Sherborn's own responsibility, readers should also take into account that nomenclatural rules have been changed or refined in the past 100 years, and that Sherborn's resource could eventually present outdated information. One of our main conclusions is that error rates in nomenclatoral compilations tend to be lower if one single and highly experienced person such as Sherborn carries out the work, than if a team is trying to do the task. Based on our experience with extracting names from original sources we came to the conclusion that error rates in such a manual work on names in a list are difficult to reduce below 2-4%. We suggest this is a natural limit and a point of diminishing returns for projects of this nature. PMID- 26877659 TI - Digitising legacy zoological taxonomic literature: Processes, products and using the output. AB - By digitising legacy taxonomic literature using XML mark-up the contents become accessible to other taxonomic and nomenclatural information systems. Appropriate schemas need to be interoperable with other sectorial schemas, atomise to appropriate content elements and carry appropriate metadata to, for example, enable algorithmic assessment of availability of a name under the Code. Legacy (and new) literature delivered in this fashion will become part of a global taxonomic resource from which users can extract tailored content to meet their particular needs, be they nomenclatural, taxonomic, faunistic or other. To date, most digitisation of taxonomic literature has led to a more or less simple digital copy of a paper original - the output of the many efforts has effectively been an electronic copy of a traditional library. While this has increased accessibility of publications through internet access, the means by which many scientific papers are indexed and located is much the same as with traditional libraries. OCR and born-digital papers allow use of web search engines to locate instances of taxon names and other terms, but OCR efficiency in recognising taxonomic names is still relatively poor, people's ability to use search engines effectively is mixed, and many papers cannot be searched directly. Instead of building digital analogues of traditional publications, we should consider what properties we require of future taxonomic information access. Ideally the content of each new digital publication should be accessible in the context of all previous published data, and the user able to retrieve nomenclatural, taxonomic and other data / information in the form required without having to scan all of the original papers and extract target content manually. This opens the door to dynamic linking of new content with extant systems: automatic population and updating of taxonomic catalogues, ZooBank and faunal lists, all descriptions of a taxon and its children instantly accessible with a single search, comparison of classifications used in different publications, and so on. A means to do this is through marking up content into XML, and the more atomised the mark-up the greater the possibilities for data retrieval and integration. Mark-up requires XML that accommodates the required content elements and is interoperable with other XML schemas, and there are now several written to do this, particularly TaxPub, taxonX and taXMLit, the last of these being the most atomised. We now need to automate this process as far as possible. Manual and automatic data and information retrieval is demonstrated by projects such as INOTAXA and Plazi. As we move to creating and using taxonomic products through the power of the internet, we need to ensure the output, while satisfying in its production the requirements of the Code, is fit for purpose in the future. PMID- 26877660 TI - The use and limits of scientific names in biological informatics. AB - Scientific names serve to label biodiversity information: information related to species. Names, and their underlying taxonomic definitions, however, are unstable and ambiguous. This negatively impacts the utility of names as identifiers and as effective indexing tools in biological informatics where names are commonly utilized for searching, retrieving and integrating information about species. Semiotics provides a general model for describing the relationship between taxon names and taxon concepts. It distinguishes syntactics, which governs relationships among names, from semantics, which represents the relations between those labels and the taxa to which they refer. In the semiotic context, changes in semantics (i.e., taxonomic circumscription) do not consistently result in a corresponding and reflective change in syntax. Further, when syntactic changes do occur, they may be in response to semantic changes or in response to syntactic rules. This lack of consistency in the cardinal relationship between names and taxa places limits on how scientific names may be used in biological informatics in initially anchoring, and in the subsequent retrieval and integration, of relevant biodiversity information. Precision and recall are two measures of relevance. In biological taxonomy, recall is negatively impacted by changes or ambiguity in syntax while precision is negatively impacted when there are changes or ambiguity in semantics. Because changes in syntax are not correlated with changes in semantics, scientific names may be used, singly or conflated into synonymous sets, to improve recall in pattern recognition or search and retrieval. Names cannot be used, however, to improve precision. This is because changes in syntax do not uniquely identify changes in circumscription. These observations place limits on the utility of scientific names within biological informatics applications that rely on names as identifiers for taxa. Taxonomic systems and services used to organize and integrate information about taxa must accommodate the inherent semantic ambiguity of scientific names. The capture and articulation of circumscription differences (i.e., multiple taxon concepts) within such systems must be accompanied with distinct concept identifiers that can be employed in association with, or in replacement of, traditional scientific names. PMID- 26877661 TI - The List of Available Names (LAN): A new generation for stable taxonomic names in zoology? AB - The List of Available Names in Zoology (LAN) is an inventory of names with specific scope in time and content, presented and approved in parts, and constituted as a cumulative index of names available for use in zoological nomenclature. It was defined in Article 79 in the fourth edition of the International Code of Zoological Nomenclature. The LAN is likely to gain importance with the development of the online Official Registry for Zoological Nomenclature (ZooBank) as it is potentially a source of many nomenclaturally certified names. Article 79 describes the deliberative process for adding large numbers of names to the LAN simultaneously, detailing steps and chronology for submission of a candidate Part to the LAN and consideration of a candidate Part by the public and Commission, but it is largely mute about the contents of a candidate Part. It does make clear that a name within the scope of a Part but not on the LAN has no nomenclatural standing, even if it had previously been considered available, thereby preventing long-forgotten names from displacing accepted ones and the accumulation of nomina dubia. Thus, for taxa on the LAN, nomenclatural archaeology - the resurrecting of old unused names to replace by priority names in current usage - will not be worthwhile. Beyond that, it has been unclear if Article 79 is intended to document every available name known within the scope of the Part, or if its intention is to pare the inventory of available names within the scope of the Part. Consideration by the Commission and two committees to deal with the LAN have defined steps to implement Article 79 with the latter intent. Procedures for consideration of a candidate Part are defined in a manual, published as an appendix in this volume. PMID- 26877662 TI - A common registration-to-publication automated pipeline for nomenclatural acts for higher plants (International Plant Names Index, IPNI), fungi (Index Fungorum, MycoBank) and animals (ZooBank). AB - Collaborative effort among four lead indexes of taxon names and nomenclatural acts (International Plant Name Index (IPNI), Index Fungorum, MycoBank and ZooBank) and the journals PhytoKeys, MycoKeys and ZooKeys to create an automated, pre-publication, registration workflow, based on a server-to-server, XML request/response model. The registration model for ZooBank uses the TaxPub schema, which is an extension to the Journal Tag Publishing Suite (JATS) of the National Library of Medicine (NLM). The indexing or registration model of IPNI and Index Fungorum will use the Taxonomic Concept Transfer Schema (TCS) as a basic standard for the workflow. Other journals and publishers who intend to implement automated, pre-publication, registration of taxon names and nomenclatural acts can also use the open sample XML formats and links to schemas and relevant information published in the paper. PMID- 26877663 TI - Surfacing the deep data of taxonomy. AB - Taxonomic databases are perpetuating approaches to citing literature that may have been appropriate before the Internet, often being little more than digitised 5 * 3 index cards. Typically the original taxonomic literature is either not cited, or is represented in the form of a (typically abbreviated) text string. Hence much of the "deep data" of taxonomy, such as the original descriptions, revisions, and nomenclatural actions are largely hidden from all but the most resourceful users. At the same time there are burgeoning efforts to digitise the scientific literature, and much of this newly available content has been assigned globally unique identifiers such as Digital Object Identifiers (DOIs), which are also the identifier of choice for most modern publications. This represents an opportunity for taxonomic databases to engage with digitisation efforts. Mapping the taxonomic literature on to globally unique identifiers can be time consuming, but need be done only once. Furthermore, if we reuse existing identifiers, rather than mint our own, we can start to build the links between the diverse data that are needed to support the kinds of inference which biodiversity informatics aspires to support. Until this practice becomes widespread, the taxonomic literature will remain balkanized, and much of the knowledge that it contains will linger in obscurity. PMID- 26877664 TI - Towards a Global Names Architecture: The future of indexing scientific names. AB - For more than 250 years, the taxonomic enterprise has remained almost unchanged. Certainly, the tools of the trade have improved: months-long journeys aboard sailing ships have been reduced to hours aboard jet airplanes; advanced technology allows humans to access environments that were once utterly inaccessible; GPS has replaced crude maps; digital hi-resolution imagery provides far more accurate renderings of organisms that even the best commissioned artists of a century ago; and primitive candle-lit microscopes have been replaced by an array of technologies ranging from scanning electron microscopy to DNA sequencing. But the basic paradigm remains the same. Perhaps the most revolutionary change of all - which we are still in the midst of, and which has not yet been fully realized - is the means by which taxonomists manage and communicate the information of their trade. The rapid evolution in recent decades of computer database management software, and of information dissemination via the Internet, have both dramatically improved the potential for streamlining the entire taxonomic process. Unfortunately, the potential still largely exceeds the reality. The vast majority of taxonomic information is either not yet digitized, or digitized in a form that does not allow direct and easy access. Moreover, the information that is easily accessed in digital form is not yet seamlessly interconnected. In an effort to bring reality closer to potential, a loose affiliation of major taxonomic resources, including GBIF, the Encyclopedia of Life, NBII, Catalog of Life, ITIS, IPNI, ICZN, Index Fungorum, and many others have been crafting a "Global Names Architecture" (GNA). The intention of the GNA is not to replace any of the existing taxonomic data initiatives, but rather to serve as a dynamic index to interconnect them in a way that streamlines the entire taxonomic enterprise: from gathering specimens in the field, to publication of new taxa and related data. PMID- 26877665 TI - An updated checklist of the ants of India with their specific distributions in Indian states (Hymenoptera, Formicidae). AB - As one of the 17 megadiverse countries of the world and with four biodiversity hotspots represented in its borders, India is home to an impressive diversity of life forms. However, much work remains to document and catalogue the species of India and their geographic distributions, especially for diverse invertebrate groups. In the present study, a comprehensive and critical list of Indian ant species is provided with up-to-date state-wise distribution. A total of 828 valid species and subspecies names belonging to 100 genera are listed from India. Potential erroneous data, misidentifications and dubious distributional records that may exist in the literature are also identified. The present exhaustive listing of Indian ants will provide a holistic view about diversity and distribution and will also help to identify major undersampled areas where future sampling and taxonomic efforts should be directed. PMID- 26877666 TI - Seven species new to science and one newly recorded species of the ant genus Myrmica Latreille, 1804 from China, with proposal of a new synonym (Hymenoptera, Formicidae). AB - Seven new species of the genus Myrmica Latreille, 1804 are described from China: Myrmica dongi sp. n., Myrmica huaii sp. n., Myrmica liui sp. n., Myrmica mifui sp. n., Myrmica oui sp. n., Myrmica wangi sp. n. and Myrmica yani sp. n. Myrmica forcipata Karawaiew, 1931 is recorded from China for the first time, while Myrmica zhengi Ma & Xu, 2011 is synonymized with Myrmica luteola Kupyanskaya, 1990. Identification keys based on worker caste are provided to the Myrmica species of China and the pachei-group species of the Old World, respectively. PMID- 26877667 TI - Leptanilla hypodracos sp. n., a new species of the cryptic ant genus Leptanilla (Hymenoptera, Formicidae) from Singapore, with new distribution data and an updated key to Oriental Leptanilla species. AB - A new species of the cryptic and rarely collected ant genus Leptanilla is described. Leptanilla hypodracos sp. n. is the first Leptanilla recorded from Singapore in over a century since Leptanilla havilandi Forel, 1901 and represents the fourth species of Leptanilla known from the Malay Peninsula. An updated key to the Leptanilla of the Oriental region is presented. Taxonomic comparisons between Leptanilla hypodracos sp. n. and four morphologically similar species are provided with particular attention given to Leptanilla clypeata Yamane & Ito, 2001, for which new measurements and indices are presented. The first report is presented for the Leptanillinae subfamily from the southeastern part of China with a worker of the genus Leptanilla collected in Hong Kong. Finally, the potential of subterranean bait to collect Leptanilla species is discussed. PMID- 26877668 TI - New species of the genus Mahinda Krombein, 1983 (Hymenoptera, Chrysididae, Amiseginae). AB - Three new species of Mahinda are described, bo from Vietnam, borneensis from Malaysian Borneo and sulawesiensis from northern Sulawesi. A key to the three known species is provided including the previously described species, saltator Krombein, 1983. PMID- 26877669 TI - A new species of Agelas from the Zanzibar Archipelago, western Indian Ocean (Porifera, Demospongiae). AB - A new sponge species (Demospongiae: Agelasida: Agelasidae) is described from the eastern coast of Unguja Island in the Zanzibar Archipelago. Agelas sansibarica sp. n. is compared to all other Agelas species described so far. The new species differs from its congeners mainly in its three categories of verticillate spicules (acanthostyles, acanthostrongyles, and acanthoxeas) and their sizes. Acanthostrongyles, well represented in the spicular complement, are an exclusive trait of the new species widening the morphological range of the genus. Summarizing on spicular complement and spicular morphotraits of 36 species belonging to the genus Agelas: i) 32 species show only acanthostyles from Indo Pacific (n = 14), Atlantic (n = 17), and Mediterranean (n = 1); ii) three Indo Pacific species show acanthostyles and acanthoxeas; iii) one species Agelas sansibarica sp. n. from the western Indian Ocean is characterised by the unique trait of three categories of verticillate spicules (acanthostyles, acanthostrongyles and acanthoxeas). A key for the Indo-Pacific species is supplied together with short descriptions, illustrations, and geographic range; literature on chemical bioprospecting of the genus Agelas is also provided. PMID- 26877670 TI - A new quadrannulate species of Orobdella (Hirudinida, Arhynchobdellida, Orobdellidae) from western Honshu, Japan. AB - A new quadrannulate species of Orobdella Oka, 1895, Orobdella naraharaetmagarum sp. n., from the mountainous region of western Honshu, Japan is described. Orobdella naraharaetmagarum is a small species with a body length of less than 5 cm. Phylogenetic analyses using nuclear 18S rRNA and histone H3, as well as mitochondrial cytochrome c oxidase subunit I, tRNA(Cys), tRNA(Met), 12S rRNA, tRNA(Val), 16S rRNA, tRNA(Leu) and NADH dehydrogenase subunit 1 markers indicated that the present new species is the sister species of the quadrannulate Orobdella esulcata Nakano, 2010. Furthermore, mitochondrial DNA genealogy within Orobdella naraharaetmagarum demonstrated that this new species is divided into eastern and western lineages. PMID- 26877671 TI - Endonura Cassagnau in Iran, with a key to species of the genus (Collembola, Neanuridae, Neanurinae). AB - Three new species of Endonura are described from Iran. Endonura dichaeta sp. n. can be recognized by an ogival labrum, head without chaetae O and E, chaeta D connected with tubercle Cl, tubercle Dl with five chaetae on head, absence of tubercles Di on thorax I and tubercle (Di+Di) of thorax V with 2+2 chaetae. Endonura ceratolabralis sp. n. is characterized by large body size, reduction of labral chaetotaxy, ogival labrum, head without chaeta O and fusion of tubercles Di and De on first thoracic segment. Endonura persica sp. n. is distinguished from its congeners by a nonogival labrum, absence of chaeta O, tubercles Dl and (L+So) with five and eight chaetae respectively and claw with inner tooth. The key to all species of the genus is given. PMID- 26877672 TI - A new Chinese Pseudoogeton species and key to the species of the genus (Coleoptera, Tenebrionidae, Amarygmini). AB - Pseudoogeton maoxianum sp. n. is described from Sichuan, China. A key to the males of the species of Pseudoogeton Masumoto, 1989 is presented. PMID- 26877673 TI - Revision of the wingless Sikkimia Duvivier (Coleoptera, Chrysomelidae, Galerucinae) from Taiwan, including a new generic synonymy and four new species descriptions. AB - The genus Taiwanolepta Kimoto, 1989 (type species Taiwanolepta babai Kimoto, 1989) is proposed as a junior synonym of Sikkimia Duvivier, 1891. Sikkimia species from Taiwan form a group characterized by the reduction of their hind wings. Most of them cannot be distinguished using external morphology, except by the structure of last two antennomeres in males. Diagnoses are made by using distribution, aedeagal, and gonocoxal morphology. The group includes one previously described species, Sikkimia babai (Kimoto, 1989), comb. n., and four new species, Sikkimia meihuai sp. n., Sikkimia sufangae sp. n., Sikkimia tsoui sp. n., and Sikkimia yuae sp. n. Speciation models, supporting the high diversity of Sikkimia species in Taiwan, are discussed. Sikkimia metallica Jacoby, 1903 and Sikkimia tamra Maulik, 1936, both from southern India, are transferred to the genus Cerophysa Chevrolat, 1836. PMID- 26877674 TI - Denopelopia amicitia, a new Tanypodinae from Brazil (Diptera, Chironomidae). AB - A new species of Denopelopia from Brazil is described based on adult male and pupa. The male of the new species can be distinguished from all other species of the genus by the genitalia and fore-tibial spur morphology. The pupa is very similar to those of Denopelopia atria, but it can be distinguished by the absence of distinct constrictions in the respiratory atrium of the thoracic horn. Generic diagnosis to male and pupa of Denopelopia is emended and keys to male and pupae of known species are provided. PMID- 26877675 TI - A review of Cyclidiinae from China (Lepidoptera, Drepanidae). AB - The subfamily Cyclidiinae from China is reviewed: two genera and seven species are reported from China. One new subspecies, Cyclidia fractifasciata indistincta subsp. n., is described. Two new synonyms are established: Cyclidia substigmaria (Hubner, 1831) (= Cyclidia substigmaria brunna Chu & Wang, 1987, syn. n. = Cyclidia tetraspota Chu & Wang, 1987, syn. n.). One misidentification in Chu & Wang (1987) is corrected. Identification keys and diagnoses for all discussed Chinese species are provided. External features and genitalia are depicted. In addition, results of DNA barcoding for five taxa of Cyclidia are briefly discussed. PMID- 26877676 TI - Corrigenda: Breedy O, Guzman HM (2015) A revision of the genus Muricea Lamouroux, 1821 (Anthozoa, Octocorallia) in the eastern Pacific. Part I: Eumuricea Verrill, 1869 revisited. ZooKeys 537: 1-32. doi: 10.3897/zookeys.537.6025. AB - [This corrects the article DOI: 10.3897/zookeys.537.6025.]. PMID- 26877677 TI - JellyWeb: an interactive information system on Scyphozoa, Cubozoa and Staurozoa. AB - Identification of organisms is traditionally based on the use of "classic" identification keys, normally printed on paper. These keys have several drawbacks: they are mainly based on the systematics, requiring identification of orders, families and genera at first; they are written by experts for other experts, in a specific scientific jargon; they have a "frozen" structure (sequence of theses/antitheses); once published, they cannot be changed or updated without printing a new edition. Due to the use of computers, it is now possible to build new digital identification tools, which: 1) can be produced automatically, if the characters are stored in a database; 2) can be freed from the traditional systematics, giving priority to easy-to-observe characters, incl. those usually uncommon to the classical keys, such as ecology and distribution; 3) can be updated in real time once published on-line; 4) can be available on different media, and on mobile devices. An important feature of these new digital tools is their "collaborative" nature. They can be enriched by the contribution of several researchers, which can cooperate while maintaining rights and property of the resources and data they contribute to the system. JellyWeb, the information system on Scyphozoa, Cubozoa and Staurozoa has been developed in Trieste since 2010. The system was created with the aim of - potentially - becoming a starting point for a wide collaborative effort in developing a user friendly worldwide digital identification system for jellyfishes. PMID- 26877678 TI - A new species of open-air processional column termite, Hospitalitermes nigriantennalis sp. n. (Termitidae), from Borneo. AB - A new species of open-air processional column termite is here described based on the soldier and worker castes from eight colonies in north Barito, central Kalimantan. Hospitalitermes nigriantennalis sp. n. is readily distinguished in the field from related Hospitalitermes spp. by the light brown to orangish coloration of the soldier head capsule that, further, is with vertex yellowish and nasus brownish. The soldier antenna and the maxillary and labial palps are blackish. By contrast, soldiers from other species of Hospitalitermes from this region have a uniformly black head capsule and antennae. Finally, Hospitalitermes nigriantennalis sp. n. has a minute indentation in the middle of the posterior part of head capsule, which further helps to differentiate this new species from other Hospitalitermes from the Indo-Malayan and Austro-Malayan regions. PMID- 26877679 TI - Two new Megalothorax species of the minimus group (Collembola, Neelidae). AB - Two new Megalothorax species, Megalothorax potapovi sp. n. from the Russian Far East and Megalothorax sanguineus sp. n. from the French Pyrenees are described. The two new species have a set of morphological characters (including a smooth mucro) that places them among the minimus group sensu Schneider and D'Haese (2013). Megalothorax potapovi characteristics include dorsal protuberance on forehead, peculiar chaetotaxy of antenna III and strong lanceolate chaetae on body. Megalothorax sanguineus characteristics include strong red pigmentation, large network of integumentary channels on head and elongated apex of the two postero-distal spines of dens. The DNA barcodes (cytochrome oxidase subunit I COI) of the two species are also provided and analyzed among a broader sampling of the genus in order to support further their specific status. A special focus is given to the labral morphological characteristics. Pseudopores-like elements are reported for the first time in the genus. Positions of the tau-chaetae near the dorsal sensory field of thorax II are compared for several species of the genus. PMID- 26877680 TI - A new, widely distributed species of the Exocelina ekari-group from West Papua (Coleoptera, Dytiscidae, Copelatinae). AB - Exocelina manokwariensis sp. n. from West Papua is placed into the Exocelina ekari-group based on the structure of its male genitalia. The new species is described, including its three subspecies, from the mainland of West Papua, Waigeo Island, Batanta and Salawati Islands, and Bomberai peninsula. An identification key to the subspecies as well as data on species distribution are provided. PMID- 26877681 TI - A new genus and nine new species of Eugnomini (Coleoptera, Curculionidae) from New Caledonia. AB - The genus Rasilinus gen. n. is described (type species Rasilinus tchambicus sp. n.). Nine new species: Rasilinus bicolor sp. n., Rasilinus bifurcatus sp. n., Rasilinus bimaculatus sp. n., Rasilinus grandidens sp. n., Rasilinus longulus sp. n., Rasilinus subgemellus sp. n., Rasilinus subnodulus sp. n., Rasilinus tchambicus sp. n., Rasilinus virgatus sp. n. are described from New Caledonia. Illustrations of the external morphology, male and female terminalia, dorsal habitus colour photographs of the adults, key to species and distribution map of the new genus Rasilinus are provided. PMID- 26877682 TI - Taxonomic review of the genus Teliphasa Moore, 1888 from China, with descriptions of four new species (Lepidoptera, Pyralidae, Epipaschiinae). AB - The genus Teliphasa Moore, 1888 from China is reviewed. Nine species are treated, including descriptions of four new species: Teliphasa spinosa Li, sp. n., Teliphasa similalbifusa Li, sp. n., Teliphasa erythrina Li, sp. n., and Teliphasa hamata Li, sp. n. Photographs of adults, wing venation, and both male and female genitalia are provided, along with a key for the identification of all the Chinese species. PMID- 26877683 TI - Annotated checklist of marine fishes from the Sanctuary of Bahia Chamela, Mexico with occurrence and biogeographic data. AB - An annotated checklist of marine fishes of the Sanctuary of Islands and Islets of Bahia Chamela in the central Mexican Pacific is presented. Records of fish species were obtained by different methods including visual census, sampling with anesthetics, fisherman-nets, and trawling with a biological dredge. Additional records were obtained from natural history collections and publications. The list comprises 196 species in 64 families and 141 genera. The Carangidae is the most speciose family with 11 species, followed by the Labridae with 10 and the Pomacentridae with nine. Fourteen species are endemic in Mexican Pacific waters, but none is restricted to Bahia Chamela. The most dominant species recorded during underwater surveys were Epinephelus labriformis, Stegastes flavilatus, and Halichoeres dispilus. Most species are of tropical affinities distributed throughout the tropical eastern Pacific (123), eastern Pacific (23), and Mexican Pacific (14). Other species are known from the eastern and Indo-Pacific regions (18), eastern Pacific and western Atlantic oceans (2), and some are circumtropical (9). A new record of the Gulf Brotula Ogilbia ventralis is provided for the Bahia Chamela and its geographical distribution is extended to Mexican central Pacific. PMID- 26877684 TI - The Vermetidae of the Gulf of Kachchh, western coast of India (Mollusca, Gastropoda). AB - Coral reefs are often termed underwater wonderlands due to the presence of an incredible biodiversity including numerous invertebrates and vertebrates. Among the dense population of benthic and bottom-dwelling inhabitants of the reef, many significant species remain hidden or neglected by researchers. One such example is the vermetids, a unique group of marine gastropods. The present study attempts for the first time to assess the density and identify preferred reef substrates in the Gulf of Kachchh, state of Gujarat, on the western coast of India. A total of three species of the family Vermetidae were recorded during the study and their substrate preferences identified. PMID- 26877686 TI - Tsukiyamaia, a new genus of the tribe Baorini (Lepidoptera, Hesperiidae, Hesperiinae). AB - Skippers of the tribe Baorini are evidently a monophyletic group in the subfamily Hesperiinae. In this study, a new Baorini member Tsukiyamaia albimacula gen. n. et sp. n. is described from north Myanmar, southwest China and north Vietnam. Despite its peculiar and striking wing-pattern, this new genus has some important characters of Baorini, such as a broad and bifid uncus and a well-developed gnathos. Based on an analysis of male genitalia and the molecular phylogenies inferred from both mitochondrial and nuclear genes (28 taxa, total aligned length: 2968 bp), it is proposed that the genus Tsukiyamaia is closely related to the genus Polytremis, which has high species diversity in China. This study not only describes a new skipper but also highlights that Tsukiyamaia is important in clarifying phylogenetic relationship of Polytremis and its allies. PMID- 26877685 TI - A new monster from southwest Oregon forests: Cryptomaster behemoth sp. n. (Opiliones, Laniatores, Travunioidea). AB - The monotypic genus Cryptomaster Briggs, 1969 was described based on individuals from a single locality in southwestern Oregon. The described species Cryptomaster leviathan Briggs, 1969 was named for its large body size compared to most travunioid Laniatores. However, as the generic name suggests, Cryptomaster are notoriously difficult to find, and few subsequent collections have been recorded for this genus. Here, we increase sampling of Cryptomaster to 15 localities, extending their known range from the Coast Range northeast to the western Cascade Mountains of southern Oregon. Phylogenetic analyses of mitochondrial and nuclear DNA sequence data reveal deep phylogenetic breaks consistent with independently evolving lineages. We use discovery and validation species delimitation approaches to generate and test species hypotheses, including a coalescent species delimitation method to test multi-species hypotheses. For delimited species, we use light microscopy and SEM to discover diagnostic morphological characters. Although Cryptomaster has a small geographic distribution, this taxon is consistent with other short-range endemics in having deep phylogenetic breaks indicative of species level divergences. Herein we describe Cryptomaster behemoth sp. n., and provide morphological diagnostic characters for identifying Cryptomaster leviathan and Cryptomaster behemoth. PMID- 26877687 TI - A new genus and species of arboreal toad with phytotelmonous larvae, from the Andaman Islands, India (Lissamphibia, Anura, Bufonidae). AB - A new bufonid amphibian, belonging to a new monotypic genus, is described from the Andaman Islands, in the Bay of Bengal, Republic of India, based on unique external morphological and skeletal characters which are compared with those of known Oriental and other relevant bufonid genera. Blythophryne gen. n. is distinguished from other bufonid genera by its small adult size (mean SVL 24.02 mm), the presence of six presacral vertebrae, an absence of coccygeal expansions, presence of an elongated pair of parotoid glands, expanded discs at digit tips and phytotelmonous tadpoles that lack oral denticles. The taxonomic and phylogenetic position of the new taxon (that we named as Blythophryne beryet gen. et sp. n.) was ascertained by comparing its 12S and 16S partial genes with those of Oriental and other relevant bufonid lineages. Resulting molecular phylogeny supports the erection of a novel monotypic genus for this lineage from the Andaman Islands of India. PMID- 26877688 TI - A new species of Liolaemus related to L. nigroviridis from the Andean highlands of Central Chile (Iguania, Liolaemidae). AB - The Liolaemus nigroviridis group is a clade of highland lizards endemic to Chile. These species are distributed from northern to central Chile, and currently there are no cases of sympatric distribution. This study describes a new species, Liolaemus uniformis sp. n., from this group, and provides a detailed morphological characterization and mitochondrial phylogeny using cytochrome-b. Liolaemus uniformis was found in sympatry with Liolaemus nigroviridis but noticeably differed in size, scalation, and markedly in the color pattern, without sexual dichromatism. This new species has probably been confused with Liolaemus monticola and Liolaemus bellii, both of which do not belong to the nigroviridis group. The taxonomic issues of this group that remain uncertain are also discussed. PMID- 26877689 TI - GPS tracking data of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast. AB - In this data paper, Bird tracking - GPS tracking of Lesser Black-backed Gulls and Herring Gulls breeding at the southern North Sea coast is described, a species occurrence dataset published by the Research Institute for Nature and Forest (INBO). The dataset (version 5.5) contains close to 2.5 million occurrences, recorded by 101 GPS trackers mounted on 75 Lesser Black-backed Gulls and 26 Herring Gulls breeding at the Belgian and Dutch coast. The trackers were developed by the University of Amsterdam Bird Tracking System (UvA-BiTS, http://www.uva-bits.nl). These automatically record and transmit bird movements, which allows us and others to study their habitat use and migration behaviour in great detail. Our bird tracking network is operational since 2013. It is funded for LifeWatch by the Hercules Foundation and maintained in collaboration with UvA BiTS and the Flanders Marine Institute (VLIZ). The recorded data are periodically released in bulk as open data (http://dataset.inbo.be/bird-tracking-gull occurrences), and are also accessible through CartoDB and the Global Biodiversity Information Facility (GBIF). PMID- 26877690 TI - Multi-locus analysis supports the taxonomic validity of Arborophila gingica guangxiensis Fang Zhou & Aiwu Jiang, 2008. AB - The taxonomic status of subspecies has long been debated, especially in conservation biology. Some proposed subspecies must be evolutionarily distinct to be considered conservation units. White-necklaced Partridge (Arborophila gingica) comprises two subspecies, Arborophila gingica gingica and Arborophila gingica guangxiensis. Arborophila gingica guangxiensis, restricted to three isolated small areas in Guangxi, China, with limited population sizes, is a newly discovered subspecies based on recently identified geographic and phenotypic differences between Arborophila gingica gingica; however, evidence is lacking that can effectively identify whether the subspecies is evolutionarily distinct. Here, three mitochondrial DNA segments and four nuclear introns were used to test whether the two subspecies are reciprocally monophyletic, which has been proposed as an objective method to evaluate evolutionary distinctiveness. The results indicate that the two subspecies are genetically divergent and form reciprocal monophyletic groups. Therefore, this study further supports the taxonomic validity and distinctiveness of Arborophila gingica guangxiensis and suggests that this subspecies be considered as a conservation unit. PMID- 26877691 TI - Depreissia decipiens, an enigmatic canopy spider from Borneo revisited (Araneae, Salticidae), with remarks on the distribution and diversity of canopy spiders in Sabah, Borneo. AB - Depreissia is a little known genus comprising two hymenopteran-mimicking species, one found in Central Africa and one in the north of Borneo. The male of Depreissia decipiens is redescribed, the female is described for the first time. The carapace is elongated, dorsally flattened and rhombus-shaped, the rear of the thorax laterally depressed and transformed, with a pair of deep pits; the pedicel is almost as long as the abdomen. The male palp is unusual, characterized by the transverse deeply split membranous tegulum separating a ventral part which bears a sclerotized tegular apophysis and a large dagger-like retrodirected median apophysis. The female epigyne consists of one pair of large adjacent spermathecae and very long copulatory ducts arising posteriorly and rising laterally alongside the spermathecae continuing in several vertical and horizontal coils over the anterior surface. Relationships within the Salticidae are discussed and an affinity with the Cocalodinae is suggested. Arguments are provided for a hypothesis that Depreissia decipiens is not ant-mimicking as was previously believed, but is a mimic of polistinine wasps. The species was found in the canopy in the Kinabalu area only, in primary and old secondary rainforest at 200 700 m.a.s.l. Overlap of canopy-dwelling spider species with those in the understorey are discussed and examples of species richness and endemism in the canopy are highlighted. Canopy fogging is a very efficient method of collecting for most arthropods. The canopy fauna adds an extra dimension to the known biodiversity of the tropical rainforest. In southeast Asia, canopy research has been neglected, inhibiting evaluation of comparative results of this canopy project with that from other regions. More use of fogging as a collecting method would greatly improve insight into the actual species richness and species distribution in general. PMID- 26877692 TI - Revision of the family Carabodidae (Acari, Oribatida) V. Fourth part. Two new species of the genus Congocepheus from the Republic of Rwanda: Congocepheus rwandensis sp. n., and Congocepheus kayoveae sp. n. AB - Two new species from Rwanda are described utilizing optical and scanning electron microscope observations: Congocepheus rwandensis sp. n. and Congocepheus kayoveae sp. n. are compared to Congocepheus taurus Balogh 1961. PMID- 26877693 TI - Mayflies, stoneflies, and caddisflies of streams and marshes of Indiana Dunes National Lakeshore, USA. AB - United States National Parks have protected natural communities for one hundred years. Indiana Dunes National Lakeshore (INDU) is a park unit along the southern boundary of Lake Michigan in Indiana, USA. An inventory of 19 sites, consisting of a seep, 12 streams, four marshes, a bog, and a fen were examined for mayflies (Ephemeroptera), stoneflies (Plecoptera), and caddisflies (Trichoptera) (EPT taxa). Volunteers and authors collect 35 ultraviolet light traps during summer 2013 and supplementary benthic and adult sampling added species not attracted by lights or that were only present in colder months. Seventy-eight EPT species were recovered: 12 mayflies, two stoneflies, and 64 caddisflies. The EPT richness found at INDU was a low proportion of the number of species known from Indiana: caddisflies contributed only 32.7% of known state fauna, mayflies and stoneflies contributed 8.4% and 2.3%, respectively. Site EPT richness ranged from one for a seep to 34 for an 8 m-wide stream. Richness in streams generally increased with stream size. Seven new state records and rare species are reported. The number of EPT species at INDU is slightly larger than that found at Isle Royale National Park in 2013, and the community composition and evenness between orders were different. PMID- 26877694 TI - A new genus and species (Cornucollis gen. n. masoalensis sp. n.) of praying mantis from northern Madagascar (Mantodea, Iridopterygidae, Tropidomantinae). AB - An examination of Malagasy specimens accessed within the Museum national d'Histoire naturelle, Paris, France, produced a praying mantis (Insecta: Mantodea) of an undescribed genus and species. An investigation of the internal and external morphology, in addition to its collection locality, revealed that this specimen belongs to the Iridopterygidae subfamily Tropidomantinae. Furthermore, the specimen's unique combination of characters justified the creation of a new genus. Geographic distributional records and external morphological character evidence are presented for Cornucollis gen. n. masoalensis sp. n. We provide a dichotomous key of the Tropidomantinae and Nilomantinae genera distributed within Madagascar. High-resolution images, illustrations of morphological characters, natural history information, and measurement data are presented. PMID- 26877695 TI - Records of Hedotettix and Teredorus in Thailand with the description of three new species (Orthoptera, Tetrigidae). AB - We are studying the fungi associated with insects in northern Thailand and as a result several rarely collected insect species have been uncovered. The genera Hedotettix with one new species and Teredorus with two new species are reported from Thailand. Hedotettix triangularis Zha & Hyde, sp. n., Teredorus chiangraiensis Zha & Hyde, sp. n. and Teredorus combfemorus Zha & Hyde, sp. n. are introduced, described and photographed and compared with other species. Keys to species of Hedotettix and Teredorus from Thailand are provided. PMID- 26877696 TI - Revision of the Australian species of the weevil genus Trigonopterus Fauvel. AB - The Australian species of the genus Trigonopterus Fauvel are revised. Eight previously recognized species are redescribed and 24 additional new species are described: Trigonopterus allaetus Riedel, sp. n., Trigonopterus athertonensis Riedel, sp. n., Trigonopterus australinasutus Riedel, sp. n., Trigonopterus australis Riedel, sp. n., Trigonopterus bisignatus Riedel, sp. n., Trigonopterus bisinuatus Riedel, sp. n., Trigonopterus boolbunensis Riedel, sp. n., Trigonopterus cooktownensis Riedel, sp. n., Trigonopterus daintreensis Riedel, sp. n., Trigonopterus deplanatus Riedel, sp. n., Trigonopterus finniganensis Riedel, sp. n., Trigonopterus fraterculus Riedel, sp. n., Trigonopterus garradungensis Riedel, sp. n., Trigonopterus hasenpuschi Riedel, sp. n., Trigonopterus hartleyensis Riedel, sp. n., Trigonopterus kurandensis Riedel, sp. n., Trigonopterus lewisensis Riedel, sp. n., Trigonopterus montanus Riedel, sp. n., Trigonopterus monteithi Riedel, sp. n., Trigonopterus mossmanensis Riedel, sp. n., Trigonopterus oberprieleri Riedel, sp. n., Trigonopterus robertsi Riedel, sp. n., Trigonopterus terraereginae Riedel, sp. n., Trigonopterus yorkensis Riedel, sp. n.. All new species are authored by the taxonomist-in-charge, Alexander Riedel. Lectotypes are designated for the following names: Idotasia aequalis Pascoe, Idotasia albidosparsa Lea, Idotasia evanida Pascoe, Idotasia laeta Lea, Idotasia rostralis Lea, Idotasia sculptirostris Lea, Idotasia squamosa Lea. A new combination of the name Idotasia striatipennis Lea is proposed: Trigonopterus striatipennis (Lea), comb. n.. A key to the species is provided. Australian Trigonopterus occur in coastal Queensland, narrowly crossing into New South Wales. The southern parts of the range are inhabited by species found on foliage. A rich fauna of 19 edaphic species inhabiting the leaf litter of tropical forests is reported for the first time from the Australian Wet Tropics. PMID- 26877697 TI - Overview of the genus Briareum (Cnidaria, Octocorallia, Briareidae) in the Indo Pacific, with the description of a new species. AB - The status of Indo-Pacific Briareum species (Cnidaria, Octocorallia, Briareidae) is reviewed by presenting their sclerite features and habitus descriptions. Following the re-examination of type material, museum specimens and newly collected specimens, a species identification key is provided. The species distributions are discussed and updated distribution ranges are depicted. Moreover, a new taxon, Briareum cylindrum sp. n. is described and depicted, whereas Briareum excavatum (Nutting, 1911) is synonymised with Briareum stechei (Kukenthal, 1908). Briareum hamrum (Gohar, 1948) is recorded from the Persian Gulf and Oman Sea for the first time. Consequently, in total four Briareum species are recognized in the Indo-Pacific; Briareum hamrum from the western Indian Ocean, and Briareum cylindrum sp. n., Briareum stechei, and Briareum violaceum from the central and eastern Indo-Pacific region. PMID- 26877698 TI - A new species of the genus Timalinyssus Mironov, 2001 (Acarina, Psoroptidia) with a key to known species. AB - The article describes a new species of the feather mite family Pteronyssidae (Acarina: Psoroptidia) from the Gray Sibia Heterophasia gracilis (McClelland) (Passeriformes, Leiothrichidae) in India (Meghalaya, Jaintia Hills, Shnongrim village). Males of Timalinyssus wahlangi sp. n. differ from those of all Timalinyssus species by having the horseshoe-shaped epiandrum with a short anterior extension. Females of the new species differ from those of all previously known species of the genus in having the hysteronotal shield with deep lateral incisions between e2 and f2 setae. A key to all species of the genus Timalinyssus is presented. PMID- 26877699 TI - A revision of Megalocraerus Lewis, 1902 (Coleoptera, Histeridae: Exosternini). AB - The formely monotypic Neotropical genus Megalocraerus Lewis is revised to include five species, known from southeastern Brazil to Costa Rica: Megalocraerus rubricatus Lewis, Megalocraerus mandibularis sp. n., Megalocraerus chico sp. n., Megalocraerus madrededios sp. n., and Megalocraerus tiputini sp. n. We describe the species, map their distributions, and provide a key for their identification. Their subcylindrical body form and emarginate mesosternum have previously hindered placement to tribe, although their curent assignment to Exosternini now appears well supported by morphological evidence. Nothing is known of the natural history of the species. PMID- 26877700 TI - A new species of Eutettix (Hemiptera, Cicadellidae, Deltocephalinae) from Wisconsin. AB - Eutettix latoides sp. n., is described from central Wisconsin. It most closely resembles the Californian species Eutettix latus Hepner, and was collected from Quercus ellipsoidalis. PMID- 26877701 TI - First Immature of the New World Treehopper tribe Thuridini (Hemiptera, Membracidae, Smiliinae) with a new synonym, a new combination, and a new country record. AB - The species Thuris depressus Sakakibara (1975) is proposed as a syn. n. of Thuris binodosus (Goding 1926), comb. n. The distribution of the genus is expanded from Brazil and Peru to include Ecuador and Venezuela, and the immature is described based on 75 characters. PMID- 26877702 TI - Descriptions of new species of the genera Sarima Melichar and Sarimodes Matsumura from southern China (Hemiptera, Fulgoromorpha, Issidae). AB - Two Issini genera, Sarima Melichar, 1903 and Sarimodes Matsumura, 1916, are examined. One new Sarima species: Sarima bifurcus sp. n. and two new Sarimodes species Sarimodes clavatus sp. n. and Sarimodes parallelus sp. n. are added from South China. A checklist of species in the genus Sarima with data on distribution is provided. The distribution and morphological peculiarities of the genera Sarima and Sarimodes are briefly discussed. PMID- 26877703 TI - Systematic revision of the Taiwanese genus Kurixalus members with a description of two new endemic species (Anura, Rhacophoridae). AB - Two new species of rhacophorid tree frog were identified in Taiwan. In both new taxa, derived reproductive characteristics of laying eggs in tree holes and oophagous tadpoles are shared with Kurixalus eiffingeri, but they are divergent from each other in molecular genetics, mating calls, and tadpole and adult morphology. The morphological characteristics and the molecular phylogenetic evidence support the hypothesis that the two new species, Kurixalus berylliniris sp. n. and Kurixalus wangi sp. n., are both monophyletic lineages. PMID- 26877704 TI - Characteristics of officer-involved vehicle collisions in California. AB - PURPOSE: The purpose of this paper is to examine the situational and individual officer characteristics of officer-involved vehicle collisions that result in fatality, injury, and non-injury outcomes. DESIGN/METHODOLOGY/APPROACH: Data on 35,840 vehicle collisions involving law enforcement officers in California occurring between January 2000 and December 2009 are examined. A descriptive analysis of collision characteristics is presented. FINDINGS: There were 39 officers killed by collisions over this study period and 7,684 officers who received some type injury. Incidents involving officers on motorcycles represented 39 percent of officer fatalities and 39 percent of severe injuries. In the case of fatalities, 33 percent of officers were reported as wearing seatbelts, 38 percent were not wearing a seatbelt, and seatbelt use was not stated in 29 percent of car fatalities. RESEARCH LIMITATIONS/IMPLICATIONS: The findings only represent one state and the analysis is based on an estimated 86 percent of collisions that occurred during the study period due to missing data. Nonetheless, the results are based on a robust sample and address key limitations in the existing literature. PRACTICAL IMPLICATIONS: During the study period in California the estimated financial impact of collisions reached into the hundreds of millions of dollars when considering related fatality, injury, and vehicle damage costs combined. These impacts highlight the need for the law enforcement community to give greater attention to this issue. ORIGINALITY/VALUE: At the time of this writing there was no published independent research that compares the situational and officer characteristics across fatality, injury, and non-injury outcomes in these events. The findings reported here will help inform emerging interest in this issue within the law enforcement, academic, and policy-making communities. PMID- 26877705 TI - Flexibility in task switching by monolinguals and bilinguals. AB - Many bilinguals routinely switch between their languages, yet mixed evidence exists about the transfer of language switching skills to broader domains that require attentional control such as task switching. Monolingual and bilingual young adults performed a nonverbal task-switching paradigm in which they viewed colored pictures of animals and indicated either the animal or its color in response to a cue. Monolinguals and bilinguals performed similarly when switching between tasks (local switch cost) in a mixed-task block, but bilinguals demonstrated a smaller mixing effect (global switch cost) than monolinguals, indicating better ability to reconfigure stimulus-response associations. These results suggest that regular practice using multiple languages confers a broader executive function advantage shown as improved flexibility in task switching. PMID- 26877707 TI - Intake and sources of dietary fatty acids in Europe: Are current population intakes of fats aligned with dietary recommendations? AB - 1The development of food-based dietary guidelines for prevention of cardiovascular diseases requires knowledge of the contribution of common foods to SFA and PUFA intake. We systematically reviewed available data from European countries on population intakes and dietary sources of total fat, SFA, and PUFA. Data from national dietary surveys or population studies published >1995 were searched through Medline, Web of Science, and websites of national public health institutes. Mean population intakes were compared with FAO/WHO dietary recommendations, and contributions of major food groups to overall intakes of fat and fatty acids were calculated. Fatty acid intake data from 24 European countries were included. Reported mean intakes ranged from 28.5 to 46.2% of total energy (%E) for total fat, from 8.9 to 15.5%E for SFA, from 3.9 to 11.3%E for PUFA. The mean intakes met the recommendation for total fat (20-35%E) in 15 countries, and for SFA (<10%E) in two countries, and for PUFA (6-11%E) in 15 of the 24 countries. The main three dietary sources of total fat and SFA were dairy, added fats and oils, and meat and meat products. The majority of PUFA in the diet was provided by added fats and oils, followed by cereals and cereal products, and meat and meat products. Practical applications: While many European countries meet the recommended intake levels for total fat and PUFA, a large majority of European population exceeds the widely recommended maximum 10%E for SFA. In particular animal based products, such as dairy, animal fats, and fatty meat contribute to SFA intake. Adhering to food-based dietary guidelines for prevention of CHD and other chronic diseases in Europe, including eating less fatty meats, low-fat instead of full-fat dairy, and more vegetable fats and oils will help to reduce SFA intake and at the same time increase PUFA intake. In European countries, SFA intakes are generally higher than the recommended <10%E and PUFA intakes lower than the recommended 6-11%E. Adhering to food-based dietary guidelines for prevention of CHD and other chronic diseases including eating leaner variants of meat and dairy, and more vegetable fats and oils will help to decrease SFA intake and increase PUFA intake. PMID- 26877706 TI - Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach. AB - Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp3)-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined. PMID- 26877708 TI - Predictors of dietary change among those who successfully lost weight in phase I of the Weight Loss Maintenance Trial. AB - AIM: Dietary changes occurring during weight loss interventions can vary. The present study tested if pretreatment psychosocial, dietary and demographic factors were associated with changes in fat intake and fruit and vegetable intake during a weight loss intervention. METHODS: This analysis includes participants who lost at least four kilograms during the initial six month weight loss phase (phase I) of the Weight Loss Maintenance Trial, a group format behavioural intervention emphasising a low-fat diet and increased physical activity. Multiple linear regression was used to determine associations between pretreatment psychosocial, dietary, physical activity, and demographic variables and changes from pretreatment to six months in fat intake and fruit and vegetable intake. RESULTS: Participants (n = 1032) were 63.4% female, 62.4% non-African American, and had a mean age of 55.6 and BMI of 34.1 kg/m2. Being African American (P < 0.0001) and higher baseline kilojoule intake (P < 0.01) were associated with smaller reductions in fat intake. Being African American (p < 0.001) and older age (P = 0.02) were associated with smaller increases in fruit and vegetable intake, whereas a history of 10 or more past weight loss episodes of at least 10 lb (4.5 kg; P < 0.01) was associated with greater increases. CONCLUSIONS: Few psychosocial factors examined contributed to variability in dietary change. Even when achieving meaningful weight losses during a behavioural weight loss intervention, African Americans may make fewer beneficial changes in fat and fruit and vegetable intake than non-African Americans. PMID- 26877709 TI - Heat shock protein 27 downstream of P38-PI3K/Akt signaling antagonizes melatonin induced apoptosis of SGC-7901 gastric cancer cells. AB - BACKGROUND: Despite the fact that melatonin treatment shows some promise in gastric cancer, the molecular mechanisms of gastric cancer cells in response to melatonin remains to be determined. METHODS: The SGC-7901 gastric cancer cells were treated with different concentrations of melatonin for 24 and 48 h. Cell viability was determined by MTT assay, Hoechst 33258 staining and FACS analysis were used to detect apoptotic cells. The contents and activation of apoptosis related proteins HSP27, Akt and P38 were evaluated by immunoblotting analysis. Then we treated SGC-7901 cells with HSP27-specific siRNA, PI3K inhibitor LY294002 or P38 inhibitor SB203580 to investigate the role of HSP27, Akt and P38 in the anti-apoptotic response of SGC-7901 cells to melatonin. RESULTS: Melatonin suppressed cell viability and stimulated apoptosis of gastric cancer SGC-7901 cells dose-dependently. Mechanistically, the observed apoptosis was accompanied by the melatonin-induced phosphorylation of HSP27. HSP27-specific siRNA transfection effectively reduced HSP27 phosphorylation and augmented melatonin induced apoptosis, indicating that HSP27 is resistant to melatonin-induced apoptosis. Moreover, melatonin increased PI3K/Akt activation, LY294002 abrogated HSP27 activation and promoted cell apoptosis induced by melatonin. Furthermore, melatonin increased P38 activity, and P38 inhibitor SB203580 inhibited melatonin induced PI3K/Akt, HSP27 activation and accelerated cell apoptosis. CONCLUSION: In contrast to the well-established anti-cancer properties of melatonin, our study revealed clearly a distinguishable anti-apoptotic pathway induced by melatonin, that is, HSP27 plays a crucial role in apoptotic resistance in melatonin-treated gastric cancer cells, and its activation is most likely via the activation of P38/PI3K/Akt signaling. PMID- 26877710 TI - Antibiotics inhibit sphere-forming ability in suspension culture. AB - BACKGROUND: This last decade, a lot of emphasis has been placed on developing new cancer cell culture models, closer to in vivo condition, in order to test new drugs and therapies. In the case of colorectal cancer, the use of patient biopsies to seed 3D primary cultures and mimic tumor initiation necessitates the use of antibiotics to prevent microbial intestinal contamination. However, not only long term use of antibiotics may mask the presence of low levels of microbial contamination, it may also impact cancer cell phenotype. METHODS: In this study we tested the impact of penicillin-streptomycin cocktail addition in both monolayer and suspension culture. To ensure the reliability of our observations we used six different cell lines and each experiment was performed in triplicate. Results were analyzed with Student's t test. RESULTS: We show that penicillin-streptomycin cocktail inhibits the sphere-forming ability of six cancer cell lines in suspension culture though it has no impact in monolayer culture. We correlate this effect with a significant decrease of cancer stem cells pool which holds self-renewal potential. CONCLUSIONS: Overall, this study warns against systematic addition of antibiotics in growth medium and raises the interesting possibility of using antibiotics to target cancer stem cells. PMID- 26877712 TI - A BioBrickTM-Compatible Vector for Allelic Replacement Using the XylE Gene as Selection Marker. AB - BACKGROUND: Circular plasmid-mediated homologous recombination is commonly used for marker-less allelic replacement, exploiting the endogenous recombination machinery of the host. Common limitations of existing methods include high false positive rates due to mutations in counter-selection genes, and limited applicability to specific strains or growth media. Finally, solutions compatible with physical standards, such as the BioBrickTM, are not currently available, although they proved to be successful in the design of other replicative or integrative plasmids. FINDINGS: We illustrate pBBknock, a novel BioBrickTM compatible vector for allelic replacement in Escherichia coli. It includes a temperature-sensitive replication origin and enables marker-less genome engineering via two homologous recombination events. Chloramphenicol resistance allows positive selection of clones after the first event, whereas a colorimetric assay based on the xylE gene provides a simple way to screen clones in which the second recombination event occurs. Here we successfully use pBBknock to delete the lactate dehydrogenase gene in E. coli W, a popular host used in metabolic engineering. CONCLUSIONS: Compared with other plasmid-based solutions, pBBknock has a broader application range, not being limited to specific strains or media. We expect that pBBknock will represent a versatile solution both for practitioners, also among the iGEM competition teams, and for research laboratories that use BioBrickTM-based assembly procedures. PMID- 26877713 TI - Work environment facilitators to the availability of complementary and alternative therapies in perinatal hospices. AB - Increasingly, patients and clinicians are considering palliative care interventions during pregnancy for the maternal-fetal dyad, when a life-limiting diagnosis is confirmed. Nurses are at the forefront of providing hospice and palliative care that includes planning interventions for infants nearing the end of life. However, little is known about the work environment facilitators to the availability of complementary and alternative medicine (CAM) therapies. Using a national database of perinatal hospice and palliative care providers, we described the types of CAM therapies available and explored the influence of the nurse work environment on the availability of CAM therapies with multivariate regression analysis. This study showed that having an education environment where clinicians are trained, along with a highly educated RN support staff, and a BSN educated staff were critical to the availability of CAM therapies. The clinical implications for hospice and palliative nurses caring for infants and their families were discussed. PMID- 26877711 TI - Effects of the lifestyle habits in breast cancer transcriptional regulation. AB - Through research carried out in the last 25 years about the breast cancer etiology, it has been possible to estimate that less than 10 % of patients who are diagnosed with the condition are carriers of some germline or somatic mutation. The clinical reports of breast cancer patients with healthy twins and the development of disease in women without high penetrance mutations detected, warn the participation more factors in the transformation process. The high incidence of mammary adenocarcinoma in the modern woman and the urgent need for new methods of prevention and early detection have demanded more information about the role that environment and lifestyle have on the transformation of mammary gland epithelial cells. Obesity, alcoholism and smoking are factors that have shown a close correlation with the risk of developing breast cancer. And although these conditions affect different cell regulation levels, the study of its effects in the mechanisms of transcriptional and epigenetic regulation is considered critical for a better understanding of the loss of identity of epithelial cells during carcinogenesis of this tissue. The main objective of this review was to establish the importance of changes occurring to transcriptional level in the mammary gland as a consequence of acute or chronic exposure to harmful products such as obesity-causing foods, ethanol and cigarette smoke components. At analyze the main studies related to topic, it has concluded that the understanding of effects caused by the lifestyle factors in performance of the transcriptional mechanisms that determine gene expression of the mammary gland epithelial cells, may help explain the development of this disease in women without genetic propensity and different phenotypic manifestations of this cancer type. PMID- 26877714 TI - CDC MessageWorks: Designing and Validating a Social Marketing Tool to Craft and Defend Effective Messages. AB - The Centers for Disease Control and Prevention's Division of Cancer Prevention and Control, in partnership with Oak Ridge Associated Universities, designed an online social marketing strategy tool, MessageWorks, to help health communicators effectively formulate messages aimed at changing health behaviors and evaluate message tactics and audience characteristics. MessageWorks is based on the advisor for risk communication model that identifies 10 variables that can be used to predict target audience intentions to comply with health recommendations. This article discusses the value of the MessageWorks tool to health communicators and to the field of social marketing by (1) describing the scientific evidence supporting use of MessageWorks to improve health communication practice and (2) summarizing how to use MessageWorks and interpret the results it produces. PMID- 26877715 TI - Nursing Perceptions of Clinical Research in the Neonatal Intensive Care Unit. AB - PURPOSE: To determine perceptions of clinical research in the NICU. DESIGN: Survey study. SAMPLE: Nurses (n=68) employed in a level III NICU in the midwestern United States. MAIN OUTCOME VARIABLE: Cross-sectional analysis of responses to a survey exploring perceptions of clinical research. RESULTS: Ninety seven percent of nurses (n=66) agree that clinical research is important for improving care, while 57% (n=39) report that it affects their day positively. Thirty-seven percent reported excellent communication between clinical and research teams. In addition, 27% (n=18) of nurses reported research presents complications for families, and 79% (n=54) reported that it is acceptable to cease a research protocol for infant benefit. Years of practice and whether nurses read research affected various responses. CONCLUSION: Clinical research is imperative to inform best practice, and nurses are an integral part of care. Therefore, it is essential to better define strategies to bridge the gap between clinical and research teams. PMID- 26877716 TI - Parenting Practices and Child Misbehavior: A Mixed Method Study of Italian Mothers and Children. AB - OBJECTIVE: The present study uses a mixed qualitative and quantitative method to examine three main research questions: What are the practices that mothers report they use when trying to correct their children's misbehaviors? Are there common patterns of these practices? Are the patterns that emerge related to children's well-being? DESIGN: Italian mother-child dyads (N=103) participated in the study (when children were 8 years of age). At Time 1 (T1), mothers answered open-ended questions about discipline; in addition, measures of maternal physical discipline and rejection and child aggression were assessed in mothers and children at T1, one year later (T2), and two years later (T3). RESULTS: Mothers' answers to open ended questions about what they would do in three disciplinary situations were classified in six categories: physical or psychological punishment, control, mix of force and reasoning, reasoning, listening, and permissiveness. Cluster analysis yielded 3 clusters: Group 1, Induction (predominant use of reasoning and listening; 74%); Group 2, Punishment (punitive practices and no reasoning; 16%); Group 3, Mixed practices (combination of reasoning and punishment, as well as high control and no listening; 10%). Multiple-group latent growth curves of maternal physical discipline, maternal rejection, and child aggression were implemented to evaluate possible differences in the developmental trends from T1 to T3, as a function of cluster. CONCLUSIONS: Qualitative data deepen understanding of parenting because they shed light on what parents think about themselves; their self-descriptions, in turn, help to identify ways of parenting that may have long-lasting consequences for children's adjustment. PMID- 26877717 TI - Ebb and Flow in Parent-Child Interactions: Shifts from Early through Middle Childhood. AB - OBJECTIVE: This study documents the strength of relations between key parent and child behaviors as they occur during typical encounters for both mothers and fathers and determines whether there were shifts in the strength of relations between parent and child behaviors during early and middle childhood. DESIGN: Multivariate multi-level modeling was used to examine associations between three parent behaviors (respect for autonomy, stimulation of development, hostility) and two child behaviors (agency, negativity) as they occurred in typical parent child activities at four time points from 54 months through 5th grade for 817 families. RESULTS: For mothers and fathers, respect for autonomy and stimulation were associated with child agency. Paternal hostility was negatively associated with child agency, but for mothers the relation became more positive with age. Parental respect for autonomy and hostility were associated with child negativity for both mothers and fathers; however, for mothers, relations between autonomy support and child negativity became more positive, and relations between hostility and child negativity became less positive. CONCLUSIONS: There are clear shifts in the strength of relations between some parenting behaviors and child behaviors from early to middle childhood, indicative of a changing dialectic as children become more independent and different dialectics for mothers and fathers. Parenting behavior links to child competence and adaptive behavior, and the findings may help resolve some uncertainties about relations between parental behavior and children's developmental trajectories. PMID- 26877718 TI - MEAN-FIELD THEORY AND COMPUTATION OF ELECTROSTATICS WITH IONIC CONCENTRATION DEPENDENT DIELECTRICS. AB - We construct a mean-field variational model to study how the dependence of dielectric coefficient (i.e., relative permittivity) on local ionic concentrations affects the electrostatic interaction in an ionic solution near a charged surface. The electrostatic free-energy functional of ionic concentrations, which is the key object in our model, consists mainly of the electrostatic potential energy and the ionic ideal-gas entropy. The electrostatic potential is determined by Poisson's equation in which the dielectric coefficient depends on the sum of concentrations of individual ionic species. This dependence is assumed to be qualitatively the same as that on the salt concentration for which experimental data are available and analytical forms can be obtained by the data fitting. We derive the first and second variations of the free-energy functional, obtain the generalized Boltzmann distributions, and show that the free-energy functional is in general nonconvex. To validate our mathematical analysis, we numerically minimize our electrostatic free-energy functional for a radially symmetric charged system. Our extensive computations reveal several features that are significantly different from a system modeled with a dielectric coefficient independent of ionic concentration. These include the non monotonicity of ionic concentrations, the ionic depletion near a charged surface that has been previously predicted by a one-dimensional model, and the enhancement of such depletion due to the increase of surface charges or bulk ionic concentrations. PMID- 26877719 TI - Teams Do It Better! AB - I propose that interdisciplinarity and respectful team science become the norm for studying human development. This is not as simple a wish as it may seem because we tend to be trained in a single discipline. We tend to know much less about the theory, methods and findings of other disciplines. We often respect them less and minimize their contributions. It is now abundantly clear, however, that humans develop on multiple levels. Human development occurs from neurons to neighborhoods, cells to societies, and genes to geography. It is fundamentally evident that every level influences the others and all combine to constitute human development. While we may specialize, certainly a reasonable personal choice, it is critical to recognize and respect the contributions of other disciplines to the study of human development. This may best be achieved by recognizing the contributions of other disciplines and working in multidisciplinary teams. PMID- 26877720 TI - Extremotolerant fungi from alpine rock lichens and their phylogenetic relationships. AB - Fungi other than the lichen mycobiont frequently co-occur within lichen thalli and on the same rock in harsh environments. In these situations dark-pigmented mycelial structures are commonly observed on lichen thalli, where they persist under the same stressful conditions as their hosts. Here we used a comprehensive sampling of lichen-associated fungi from an alpine habitat to assess their phylogenetic relationships with fungi previously known from other niches. The multilocus phylogenetic analyses suggest that most of the 248 isolates belong to the Chaetothyriomycetes and Dothideomycetes, while a minor fraction represents Sordariomycetes and Leotiomycetes. As many lichens also were infected by phenotypically distinct lichenicolous fungi of diverse lineages, it remains difficult to assess whether the culture isolates represent these fungi or are from additional cryptic, extremotolerant fungi within the thalli. Some of these strains represent yet undescribed lineages within Chaethothyriomycetes and Dothideomycetes, whereas other strains belong to genera of fungi, that are known as lichen colonizers, plant and human pathogens, rock-inhabiting fungi, parasites and saprotrophs. The symbiotic structures of the lichen thalli appear to be a shared habitat of phylogenetically diverse stress-tolerant fungi, which potentially benefit from the lichen niche in otherwise hostile habitats. PMID- 26877721 TI - Topology and temperature dependence of the diffuse X-ray scattering in Na0.5Bi0.5TiO3 ferroelectric single crystals. AB - The results of high-resolution measurements of the diffuse X-ray scattering produced by a perovskite-based Na0.5Bi0.5TiO3 ferroelectric single crystal between 40 and 620 K are reported. The study was designed as an attempt to resolve numerous controversies regarding the average structure of Na0.5Bi0.5TiO3, such as the mechanism of the phase transitions between the tetragonal, P4bm, and rhombohedral | monoclinic, R3c | Cc, space groups and the correlation between structural changes and macroscopic physical properties. The starting point was to search for any transformations of structural disorder in the temperature range of thermal depoling (420-480 K), where the average structure is known to remain unchanged. The intensity distribution around the {032} pseudocubic reflection was collected using a PILATUS 100K detector at the I16 beamline of the Diamond Light Source (UK). The data revealed previously unknown features of the diffuse scattering, including a system of dual asymmetric L-shaped diffuse scattering streaks. The topology, temperature dependence, and relationship between Bragg and diffuse intensities suggest the presence of complex microstructure in the low temperature R3c | Cc phase. This microstructure may be formed by the persistence of the higher-temperature P4bm phase, built into a lower-temperature R3c | Cc matrix, accompanied by the related long-range strain fields. Finally, it is shown that a correlation between the temperature dependence of the X-ray scattering features and the temperature regime of thermal depoling is present. PMID- 26877722 TI - The creation of a superstitious belief regarding putters in a laboratory-based golfing task. AB - The objective was to determine the extent to which it was possible to induce superstitious behaviour and beliefs in a golf putting task in a laboratory. Participants (N = 28) took part in a putting task using three identical clubs in which visual feedback regarding performance was restricted. Participants were provided with verbal feedback of their performance, which was honest when they used one putter, negative with a second putter (they did better than they were told) and positive with a third (they did worse than they were told). After this initial acquisition phase, a competition was announced and participants were asked to select a putter they would like to use. The participants were then asked to rate various qualities of the putters. Significantly more participants selected the "positive" putter for the competition (N = 22) compared to the "negative" putter (N = 1), p < .001. In addition, participants claimed that the positive putter had a better weight, was more comfortable and easier to use than the negative putter (all p < .001). Overall, this evidence can be taken to show that a superstitious belief can be formed in a short amount of time within a laboratory setting and that it can affect both the perceptions and choices of an individual. PMID- 26877724 TI - Relationship between digital information and thermodynamic stability in bacterial genomes. AB - Ever since the introduction of the Watson-Crick model, numerous efforts have been made to fully characterize the digital information content of the DNA. However, it became increasingly evident that variations of DNA configuration also provide an "analog" type of information related to the physicochemical properties of the DNA, such as thermodynamic stability and supercoiling. Hence, the parallel investigation of the digital information contained in the base sequence with associated analog parameters is very important for understanding the coding capacity of the DNA. In this paper, we represented analog information by its thermodynamic stability and compare it with digital information using Shannon and Gibbs entropy measures on the complete genome sequences of several bacteria, including Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Streptomyces coelicolor (S. coelicolor), and Salmonella typhimurium (S. typhimurium). Furthermore, the link to the broader classes of functional gene groups (anabolic and catabolic) is examined. Obtained results demonstrate the couplings between thermodynamic stability and digital sequence organization in the bacterial genomes. In addition, our data suggest a determinative role of the genome-wide distribution of DNA thermodynamic stability in the spatial organization of functional gene groups. PMID- 26877723 TI - Prospects and Pits on the Path of Biomimetics: The case of tooth enamel. AB - This review presents a discourse on challenges in understanding and imitating the process of amelogenesis in vitro on the molecular scale. In light of the analysis of imitation of the growth of dental enamel, it also impends on the prospects and potential drawbacks of the biomimetic approach in general. As the formation of enamel proceeds with the protein matrix guiding the crystal growth, while at the same time conducting its own degradation and removal, it is argued that three aspects of amelogenesis need to be induced in parallel: a) crystal growth; b) protein assembly; c) proteolytic degradation. A particular emphasis is therefore placed on ensuring conditions for proteolysis-coupled protein-guided crystallization to occur. Discussed are structural and functional properties of the protein species involved in amelogenesis, mainly amelogenin and enamelysin, the main protein and the protease of the developing enamel matrix, respectively. A model of enamel growth based on controlled delivery of constituent ions or crystalline or amorphous building blocks by means of amelogenin is proposed. The importance of high viscosity of the enamel matrix and a more intricate role that water may play in such a gelatinous medium are also touched upon. The tendency of amelogenin to self-assemble into fibrous and rod-shaped morphologies is considered as potentially important in explaining the formation of elongated apatite crystals. The idea that a preassembling protein matrix serves as a template for the uniaxial growth of apatite crystals in enamel is finally challenged with the one based on co-assembly of the protein and the mineral phases. PMID- 26877725 TI - Post-vaccination myositis and myocarditis in a previously healthy male. AB - BACKGROUND: The immunological literature has been redefining clinical phenomena as hypotheses emerge regarding causal links between triggers, immunologic manifestations, and their specific inflammatory cascades. Of late, autoimmune manifestations that appear to be caused by an external adjuvant have been grouped into a complex syndrome referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome may present with diverse clinical problems, which may include neurocognitive impairment, inflammatory musculoskeletal changes, and constitutional symptoms. There is evidence in the literature linking vaccines to different auto-immune manifestations. Vaccines have not traditionally been reported to trigger ASIA, although reports are emerging linking the human papilloma virus and hepatitis B vaccines to it. CASE PRESENTATION: We report the first suspected case of ASIA in a previously healthy patient who received the Fluad seasonal influenza vaccine, which contains the MF59 adjuvant. He presented to hospital with profound weakness and was diagnosed with severe rhabdomyolysis. He also had elevated troponin-I and extensive cardiac investigations enabled the diagnosis of myocarditis. His infectious and rheumatologic work-ups were negative. He responded well to conservative management and did not require immune suppressive therapy. CONCLUSION: Given the benefits of the influenza vaccine, and the low incidence of clinically significant complications, we encourage ongoing seasonal influenza immunization. However, ongoing surveillance is required to evaluate the occurrence of rare adverse events, including ASIA. PMID- 26877726 TI - Flexural Strength of Cold and Heat Cure Acrylic Resins Reinforced with Different Materials. AB - OBJECTIVES: Heat-polymerized acrylic resin has been the most commonly used denture base material for over 60 years. However, the mechanical strength of acrylic resin is not adequate for long-term clinical performance of dentures. Consequently, fracture is a common clinical occurrence, which often develops in the midline of the denture base. This study aimed to evaluate the efficacy of cold-cure and heat-cure acrylic resins, reinforced with glass fibers, polyethylene fibers, and metal wire for denture base repair. MATERIALS AND METHODS: Ninety specimens were prepared and allocated to nine groups. Ten specimens were considered as controls, and 80 were divided into 8 experimental groups. In the experimental groups, the specimens were sectioned into two halves from the middle, and were then divided into two main groups: one group was repaired with heat cure acrylic resin, and the other with cold cure acrylic resin. Each group was divided into 4 subgroups: unreinforced, reinforced with glass fibers, polyethylene fibers, and metal wire. All specimens were subjected to a 3-point bending test, and the flexural strength was calculated. RESULTS: The group repaired with heat cure acrylic resin and reinforced with glass fiber showed the highest flexural strength; however, the group repaired with cold cure acrylic resin and reinforced with polyethylene fibers had the lowest flexural strength. There was no significant difference between the groups repaired with heat cure and cold cure acrylic resins without reinforcement. CONCLUSION: Repairing denture base with heat cure acrylic resin, reinforced with glass fibers increases the flexural strength of denture base. PMID- 26877727 TI - Comparison of Radiography, Laser Fluorescence and Visual Examination for Diagnosing Incipient Occlusal Caries of Permanent First Molars. AB - OBJECTIVES: Early diagnosis of incipient and non-cavitated carious lesions is crucial for performing preventive treatments. The aim of this study was to compare the efficacy of three diagnostic methods of bitewing radiography, DIAGNOdent, and visual examination in diagnosing incipient occlusal caries of permanent first molars. MATERIALS AND METHODS: In this diagnostic cross-sectional study, 109 permanent first molar teeth of 31 patients aged 7-13 years were examined visually, on bitewing radiographs, and using DIAGNOdent. Scoring of visual and radiographic examinations was based on Ekstrand's classification. Visual examination after pit and fissure opening served as the gold standard. Receiver Operating Characteristic (ROC) curve was used to define the best cutoff point for DIAGNOdent compared with the gold standard. Inter-examiner reproducibility of visual and radiographic examinations was assessed using Kappa test and intraclass correlation coefficient (ICC) was calculated for DIAGNOdent values. RESULTS: The sensitivity of detecting caries that had extended into the enamel was 81.4%, 86.3%, and 81.4% for visual examination, DIAGNOdent and radiography, respectively. Moreover, the specificity was 100%, 71.4%, and 100% for visual observation, DIAGNOdent and radiography, respectively in the enamel. The Kappa index for inter-examiner reliability was 0.7 and 0.8 for visual examination and radiography, respectively. The ICC was 0.98 for the values read by DIAGNOdent. CONCLUSION: Visual examination is the first choice for diagnosis of incipient caries. In suspicious cases, radiography and laser DIAGNOdent can be used as adjunct procedures. PMID- 26877728 TI - Does Smoking Hamper Oral Self-Care Among Dental Professionals? AB - OBJECTIVES: Smoking may impact oral self-care (OSC). This study aimed to analyze the role of smoking in OSC among Iranian dental health professionals. MATERIALS AND METHODS: The cross-sectional data were collected at two annual dental meetings and seven randomly selected dental schools in Iran. A total of 1,459 respondents composed of 967 general dental practitioners (GDPs), 229 dental educators (DE), and 263 senior dental students (DS) anonymously completed a self administered questionnaire inquiring about smoking status and OSC. RESULTS: Thirty percent of the male and 12% of the female dental health professionals reported smoking tobacco. There was no difference between their professional status. Women reported better OSC than did men, but only 26% of the women and 17% of the men followed the three most important recommendations for OSC. Smoking was associated with infrequent tooth brushing and flossing, irregular use of fluoride containing toothpaste, consumption of sugary snacks and weak adherence to the recommended OSC guidelines. CONCLUSION: Dental health education should place more emphasis on smoking counseling and cessation among dental health professionals. PMID- 26877729 TI - Level of Oxidative Stress Markers in Peri-Implant Crevicular Fluid and Their Correlation with Clinical Parameters. AB - OBJECTIVES: Increased levels of oxidative stress markers in periodontitis have been reported by recent studies. Malondialdehyde (MDA) and superoxide dismutase (SOD) are both increased during oxidative stress. The aim of this study was to detect and measure the level of oxidative stress markers in peri-implant crevicular fluid (PICF). Their correlation with peri-implant clinical parameters was investigated as well. MATERIALS AND METHODS: PICF samples of 50 dental implants were collected in 31 patients. Peri-implant clinical parameters including probing pocket depth (PPD), gingival index (GI) and bleeding on probing (BOP) were recorded. Levels of oxidative stress markers including MDA, SOD and total antioxidant capacity (TAC) in PICF were determined. RESULTS: Twenty four implants showed signs of inflammation and 26 implants had healthy peri-implant tissues. MDA and TAC were detected in all samples, but SOD was not detected around 31 implants. The differences between the two groups with respect to the levels of MDA, TAC and SOD in PICF were not statistically significant (P> 0.05). In addition, significant correlations were observed between PPD and TAC and MDA level (P<0.05). CONCLUSION: Significant correlations exist between PPD and level of MDA and TAC. Moreover, level of oxidative stress markers (MDA, SOD and TAC) in PICF does not significantly change in peri-implantitis compared to healthy implants. Measuring these markers in PICF does not seem to be helpful for discrimination of peri-implant health and disease status. PMID- 26877730 TI - Cementogenesis in Patients with Localized Aggressive Periodontitis. AB - OBJECTIVES: The aim of this study was to determine the cementum thickness in the first molars of patients with localized aggressive periodontitis (LAP) compared to healthy individuals. MATERIALS AND METHODS: This case-control study compared eight first molar teeth affected by LAP with eight third molar teeth of healthy individuals. The teeth were disinfected by immersion in 10% buffered formalin solution for three days and were then sectioned. External mesial root surfaces (middle one-third) were evaluated under a stereomicroscope by a blinded pathologist to determine the mean thickness of cementum. SPSS software (version 16.0) and t-test were used for statistical analysis. RESULTS: Histological examination revealed a significant difference between the two groups in terms of the amount of cementogenesis (P<0.001) .The thickness of cementum was higher in the control group (105.16+/-11.5 MUm) than in LAP patients (86.44+/-7.3 MUm). CONCLUSION: This study demonstrated the presence of cementum hypoplasia in mesial root surfaces of first molars affected by LAP. PMID- 26877731 TI - Cytotoxic Effects and Osteogenic Activity of Calcium Sulfate with and without Recombinant Human Bone Morphogenetic Protein 2 and Nano-Hydroxyapatite Adjacent to MG-63 Cell Line. AB - OBJECTIVES: The aim of this study was to assess the cytotoxic effects and osteogenic activity of recombinant human bone morphogenetic protein (rhBMP2) and nano-hydroxyapatite (n-HA) adjacent to MG-63 cell line. MATERIALS AND METHODS: To assess cytotoxicity, the 4,5-dimethyl thiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay was used. Alkaline phosphatase (ALP) activity and osteogenic activity were evaluated using Alizarin red and the von Kossa staining and analyzed by one way ANOVA followed by Tukey's post hoc test. RESULTS: The n-HA/calcium sulfate (CS) mixture significantly promoted cell growth in comparison to pure CS. Moreover, addition of rhBMP2 to CS (P=0.02) and also mixing CS with n-HA led to further increase in extracellular calcium production and ALP activity (P=0.03). CONCLUSION: This in vitro study indicates that a scaffold material in combination with an osteoinductive material is effective for bone matrix formation. PMID- 26877733 TI - Childhood Oral Lichen Planus: Report of Two Cases. AB - Lichen planus (LP) is a chronic mucocutaneous disease widely recognized in adults, but uncommon in children. The purpose of this paper is to report two cases of LP in children. The diagnosis was made based on clinical and histopathological findings. The treatment consisted of antifungal and multivitamin therapy. Regression of lesions was observed. The patients are still under follow-up. Although LP is uncommon in children, it is necessary to have adequate knowledge about this condition for proper diagnosis and treatment. PMID- 26877732 TI - A Nanocomposite Shield Constructed for Protection Against the Harmful Effects of Dental X-Rays. AB - OBJECTIVES: This study aimed to compare a number of new nano-composites capable of protecting the jaw from ionizing radiation. MATERIALS AND METHODS: Four different types of nano-powders [Ti, Zr (IV) oxide, Ag and Co] were mixed in a polymer matrix to create nano-composites with doping values of 8% in weight. Small-angle X-ray scattering (SAXS) analysis was performed using a HECUSSAXS system with 50 kV- 50 mA. Co nano-composites (Co-pnm) yielded the most promising values of the four nanocomposites tested in terms of X-ray absorption. Thus, 4*2 cm Co-pnm samples of different thicknesses (0.20, 0.50, 0.57 and 0.60 cm) were prepared, and SAXS analysis was performed in order to assess the effects of material thickness on xray absorption. An experimental multi part shield was constructed from Co-pnm around tooth #36 to test the effect of nanomaterial on the image quality under X-ray beam. RESULTS: Logarithmic distributions of the transmitted intensity values (I) showed that 0.20 cm Co-pnm had the highest transmission value (16.05) followed by 0.50 cm Co-pnm (15.44), 0.57 cm Co-pnm (15.07) and 0.60 cm Co-pnm (15.06). The 0.2 cm Co-pnm had an effective radius of the nano-aggregation value (77.44 A) lower than that of the other thicknesses (0.50, 0.57 and 0.60 cm) of Co-pnm, which had similar values ranging from 66.22 to 66.34 A. The 0.50 cm Co-pnm had the lowest Dmax value of the different thicknesses of Co-pnm tested. CONCLUSION: Co nanocomposite can be used as a protection shield for the harmful effects of dental X-ray. PMID- 26877734 TI - Multiple Developmental Dental Anomalies in a Non-Syndromic Patient: Report of a Rare Simultaneous Occurrence. AB - A case of multiple pulp stones, a supernumerary tooth and a congenitally missing tooth accompanied by several developmental dental anomalies concurrently affecting the upper and lower anterior teeth in an Iranian healthy girl is reported. Developmental tooth abnormalities are usually found in conjunction with certain diseases or conditions. In the present case, although the patient had consanguineous parents and the role of genetics should be considered particularly for autosomal recessive traits, based on the child's family and medical history, no correlation could be established between dental findings and systemic or metabolic diseases. PMID- 26877735 TI - Clinical Course and Treatment of a Triplication Defect: A Case Report. AB - Fusion is an anomaly manifested in both deciduous and permanent dentitions. Fusion of dental tissues in the primary dentition is of clinical significance owing to the challenges in treatment of the affected teeth and aberrations encountered in development and eruption of their successors. Triple tooth refers to the union of three separate tooth entities. It can occur by fusion, germination, concrescence or a combination of both fusion and germination. Triplication is rarely encountered in the deciduous dentition. The case presented herein describes triplication of deciduous incisors and a supernumerary tooth. The diagnosis was confirmed with the help of radiographs, computed tomography (CT) imaging and histological examination. Retention of the triple tooth had led to crossbite. Extraction was performed for the triple tooth and crossbite was corrected using a composite inclined plane. PMID- 26877736 TI - Ex Vivo Comparison of Mtwo and RaCe Rotary File Systems in Root Canal Deviation: One File Only versus the Conventional Method. AB - OBJECTIVES: Cleaning and shaping of the root canal system is an important step in endodontic therapy. New instruments incorporate new preparation techniques that can improve the efficacy of cleaning and shaping. The aim of this study was to compare the efficacy of Mtwo and RaCe rotary file systems in straightening the canal curvature using only one file or the conventional method. MATERIALS AND METHODS: Sixty mesial roots of extracted human mandibular molars were prepared by RaCe and Mtwo nickel-titanium (NiTi) rotary files using the conventional and only one rotary file methods. The working length was 18 mm and the curvatures of the root canals were between 15-45 degrees . By superimposing x-ray images before and after the instrumentation, deviation of the canals was assessed using Adobe Photoshop CS3 software. Preparation time was recorded. Data were analyzed using three-way ANOVA and Tukey's post hoc test. RESULTS: There were no significant differences between RaCe and Mtwo or between the two root canal preparation methods in root canal deviation in buccolingual and mesiodistal radiographs (P>0.05). Changes of root canal curvature in >35 degrees subgroups were significantly more than in other subgroups with smaller canal curvatures. Preparation time was shorter in one file only technique. CONCLUSION: According to the results, the two rotary systems and the two root canal preparation methods had equal efficacy in straightening the canals; but the preparation time was shorter in one file only group. PMID- 26877737 TI - Water Sorption and Flexural Strength of Thermoplastic and Conventional Heat Polymerized Acrylic Resins. AB - OBJECTIVES: The aim of this study was to assess and compare the water sorption and flexural strength of thermoplastic and conventional acrylic resins. MATERIALS AND METHODS: Water sorption and flexural strength were compared between a thermoplastic modified polymethyl methacrylate (PMMA) denture base resin (group A) and a heat-polymerized PMMA acrylic resin (group B) as the control group (n=10). A three-point bending test was carried out for flexural strength testing. For water sorption test, 10 disc-shaped samples were prepared. After desiccating, the samples were weighed and immersed in distilled water for seven days. Then, they were weighed again, and desiccated for the second and third times. Differences between the mean values in the two groups were analyzed using Student's t-test. RESULTS: The mean value of water sorption was 14.74+/-1.36 MUg/mm(3) in group A, and 19.11+/-0.90 MUg/mm(3) in group B; this difference was statistically significant (P< 0.001). The mean value of flexural strength was 88.21+/-8.63 MPa in group A and 77.77+/-9.49 MPa in group B. A significant difference was observed between the two groups (P= 0.019). CONCLUSION: Flexural strength of group A was significantly higher than that of group B, and its water sorption was significantly lower. Thus, thermoplastic resins can be a suitable alternative to conventional PMMA acrylic resins as denture base materials. PMID- 26877738 TI - A Digital Stereomicroscopic Study of the Radicular Wall Thickness of Two-Canal Mandibular Incisors. AB - OBJECTIVES: This study aimed to assess the radicular wall thickness in mandibular incisors with two canals and find the maximum and minimum thickness to prevent root canal treatment (RCT) procedural errors. MATERIALS AND METHODS: A total of 160 extracted mandibular incisors were selected and radiographed; out of which, 55 had two canals. Three parallel transverse sections were made in each tooth at 1mm below the cementoenamel junction (CEJ), mid-root and 1 millimeter to the apex. Specimens were evaluated under a stereomicroscope and the thickness of radicular walls in each section was determined for the buccal, lingual and proximal surfaces. Data were statistically analyzed using Pearson's correlation coefficient test. RESULTS: The thickness of radicular wall decreased from the cervical towards the apex. In all three sections (cervical, mid-root and apical), the thickness of lingual wall was significantly greater than the buccal wall. Also, the thickness of buccal and lingual walls was significantly higher than that of the proximal walls. CONCLUSION: The lingual radicular wall had the highest thickness in two-canal mandibular incisors. Therefore, in these teeth, the lingual canal is a better choice for post placement. PMID- 26877739 TI - Which Factors Affect Dental Esthetics and Smile Attractiveness in Orthodontically Treated Patients? AB - OBJECTIVES: This study aimed to find the factors that affect dental esthetics and smile attractiveness in orthodontically treated patients according to laypeople's judgment, and to determine whether there is any relationship between dental and smile esthetics. MATERIALS AND METHODS: Using the Q-sort technique, 60 laypersons (30 males, 30 females) rated dental and smile photographs of 48 orthodontically treated patients based on their degree of attractiveness. Dental and smile parameters of each rated image were measured by Smile Analyzer software. The Student's t-test and chi-square test were used to compare dental and smile parameters between attractive and unattractive images. The logistic regression was used to assess which variables predicted dental and smile esthetics in treated individuals. RESULTS: The philtral to commissural height ratio and gingival display were significantly different in attractive and unattractive smiles (P=0.003 and P=0.02, respectively). None of the dental variables were found to be a determinant of dental esthetics at the end of the orthodontic treatment (P>0.05). According to the judgment of all raters (female and male) and the male raters' judgment, smile attractiveness could be predicted by philtral to commissural height ratio and buccal corridor ratio (P<0.05). There was no statistically significant relationship between dental esthetics and smile attractiveness in orthodontically treated patients (P>0.05). CONCLUSION: The philtral to commissural height ratio and buccal corridor ratio can be considered as predictors of smile attractiveness in orthodontically treated patients. Achieving dental esthetics at the end of orthodontic treatment does not guarantee smile attractiveness. PMID- 26877740 TI - Effects of Plasma Rich in Growth Factors and Platelet-Rich Fibrin on Proliferation and Viability of Human Gingival Fibroblasts. AB - OBJECTIVES: Platelet preparations are commonly used to enhance bone and soft tissue regeneration. Considering the existing controversies on the efficacy of platelet products for tissue regeneration, more in vitro studies are required. The aim of the present study was to compare the in vitro effects of plasma rich in growth factors (PRGF) and platelet-rich fibrin (PRF) on proliferation and viability of human gingival fibroblasts (HGFs). MATERIALS AND METHODS: Anitua's PRGF and Choukran's PRF were prepared according to the standard protocols. After culture periods of 24, 48 and 72 hours, proliferation of HGFs was evaluated by the methyl thiazol tetrazolium assay. Statistical analysis was performed using one-way ANOVA followed by Tukey-Kramer's multiple comparisons and P-values<0.05 were considered statistically significant. RESULTS: PRGF treatment induced statistically significant (P<0.001) proliferation of HGF cells compared to the negative control (100% viability) at 24, 48 and 72 hours in values of 123%+/ 2.25%, 102%+/-2.8% and 101%+/-3.92%, respectively. The PRF membrane treatment of HGF cells had a statistically significant effect on cell proliferation (21%+/ 1.73%, P<0.001) at 24 hours compared to the negative control. However, at 48 and 72 hours after treatment, PRF had a negative effect on HGF cell proliferation and caused 38% and 60% decrease in viability and proliferation compared to the negative control, respectively. The HGF cell proliferation was significantly higher in PRGF than in PRF group (P< 0.001). CONCLUSION: This study demonstrated that PRGF had a strong stimulatory effect on HGF cell viability and proliferation compared to PRF. PMID- 26877741 TI - Accuracy of Cone Beam Computed Tomography for Detection of Bone Loss. AB - OBJECTIVES: Bone assessment is essential for diagnosis, treatment planning and prediction of prognosis of periodontal diseases. However, two-dimensional radiographic techniques have multiple limitations, mainly addressed by the introduction of three-dimensional imaging techniques such as cone beam computed tomography (CBCT). This study aimed to assess the accuracy of CBCT for detection of marginal bone loss in patients receiving dental implants. MATERIALS AND METHODS: A study of diagnostic test accuracy was designed and 38 teeth from candidates for dental implant treatment were selected. On CBCT scans, the amount of bone resorption in the buccal, lingual/palatal, mesial and distal surfaces was determined by measuring the distance from the cementoenamel junction to the alveolar crest (normal group: 0-1.5mm, mild bone loss: 1.6-3mm, moderate bone loss: 3.1-4.5mm and severe bone loss: >4.5mm). During the surgical phase, bone loss was measured at the same sites using a periodontal probe. The values were then compared by McNemar's test. RESULTS: In the buccal, lingual/palatal, mesial and distal surfaces, no significant difference was observed between the values obtained using CBCT and the surgical method. The correlation between CBCT and surgical method was mainly based on the estimation of the degree of bone resorption. CBCT was capable of showing various levels of resorption in all surfaces with high sensitivity, specificity, positive predictive value and negative predictive value compared to the surgical method. CONCLUSION: CBCT enables accurate measurement of bone loss comparable to surgical exploration and can be used for diagnosis of bone defects in periodontal diseases in clinical settings. PMID- 26877742 TI - Evaluation of Periodontal Ligament Cell Viability in Three Different Storage Media: An in Vitro Study. AB - OBJECTIVES: This study was undertaken to evaluate the viability of periodontal ligament (PDL) cells of avulsed teeth in three different storage media. MATERIALS AND METHODS: Forty-five premolars extracted for orthodontic therapeutic purposes were randomly and equally divided into three groups based on storage media used [Group I: milk (control); Group II: aloe vera (experimental); Group III: egg white (experimental)]. Following extractions, the teeth were placed in one of the three different storage media for 30 minutes, following which the scrapings of the PDL from these teeth were collected in Falcon tubes containing collagenase enzyme in 2.5 mL of phosphate buffered saline. The tubes were subsequently incubated for 30 minutes and centrifuged for five minutes at 800 rpm. The obtained PDL cells were stained with Trypan Blue and were observed under optical microscope. The percentage of viable cells was calculated. RESULTS: Aloe vera showed the highest percentage of viable cells (114.3+/-8.0), followed by egg white (100.9+/-6.3) and milk (101.1+/-7.3). CONCLUSION: Within the limitations of this study, it appears that aloe vera maintains PDL cell viability better than egg white or milk. PMID- 26877743 TI - Ultrasonic Technique to Retrieve a Rotary Nickel-Titanium File Broken Beyond the Apex and a Stainless Steel File from the Root Canal of a Mandibular Molar: A Case Report. AB - During endodontic treatment, clinicians may face endodontic procedural mishaps such as broken instruments, which is a complex situation especially when the file breaks beyond the apex. This condition is associated with potential risk of contamination, which compromises the healing process. Management of a broken instrument beyond the apex is difficult and time consuming and requires creativity as well as clinical knowledge and skills. Several devices and techniques have been developed to retrieve the fractured instruments, but none are consistently successful. This case report describes a technique using modern ultrasonic tips for retrieval of broken instruments separated beyond the apex. PMID- 26877744 TI - Palisaded Encapsulated Neuroma of the Tongue Clinically Mimicking a Pyogenic Granuloma: A Case Report and Review of Literature. AB - Palisaded encapsulated (solitary circumscribed) neuromas (PENs) are relatively common intraoral neurogenic tumors, which occur most frequently on the hard palate. Herein, we describe the clinicopathological characteristics of a palisaded encapsulated neuroma of the tongue. This tumor was an exophytic sessile mass measuring 0.3* 0.4 cm with rubbery consistency on the anterior one-third of the dorsum of the tongue. The tumor was excised under the impression of a pyogenic granuloma (PG). No recurrence was reported at 12 months postoperatively. Histopathological examination showed a well-circumscribed mass that composed of interlacing fascicles of spindle cells. The cells were S-100 positive. The nuclei, showing parallel orientation within the fascicles, were wavy and pointed and showed no sign of mitotic activity. Giemsa staining revealed no mast cells within the stroma. PMID- 26877745 TI - Rehabilitation of Avulsed Teeth in Fractured Jaws via Bone Grafting and Implant Placement: Report of Two Cases. AB - The maxillofacial region is one of the most injury-prone areas during road traffic accidents, personal violence, falls and sports. Maxillofacial trauma can lead to breakage or avulsion of upper anterior teeth, which may cause significant aesthetic and functional problems. There are many treatment options available for rehabilitation including removable partial dentures, fixed partial dentures, crown and bridges and implant-supported prostheses. Herein, two cases are presented where implant placement was done for upper anterior teeth, which were traumatized or avulsed following maxillofacial trauma. Both patients demonstrated a history of maxillofacial trauma and had undergone open reduction and internal fixation. The first patient had a severe maxillary alveolar defect treated via autogenous bone grafting and a six-month period was given for proper integration of the bone graft. The second patient was a smoker with very poor oral hygiene and a deep bite. Thus, implant placement was not initially justified. PMID- 26877746 TI - Cigarette Smoking and its Relationship with Perceived Familial Support and Religiosity of University Students in Tabriz. AB - OBJECTIVE: The goal of the present study was to assess the prevalence of cigarette smoking and its relationship to other risk taking behaviors, perceived familial support and religiosity among college students in Tabriz, Iran. METHOD: In this study, 1837 randomly selected students participated and completed a self administered questionnaire inquiring demographic characteristics, risk taking behaviors, Aneshensel and Sucoff's 13-items one-dimensional perceived Parental support scale and 28 - items Kendler's general religiosity scale. RESULTS: In general, 15.8 % of the students were cigarette smokers. The results indicated that being male (OR = 3.21), living alone or with friends (OR = 2.00), having a part-time job (OR = 1.98), alcohol consumption during the past 30 days (OR = 3.67), hookah use (OR = 5.23), substance abuse (OR = 1.69), familial support (OR = 0.97) and religiosity (OR = 0.98) have statistically significant relationships with cigarette smoking. CONCLUSION: Our study represents the co-occurrence of risky behaviors. Cultural context in the traditional communities seems to show the crucial role of familial support and religiosity traits with the female gender as predictive factors to not smoke cigarette and perform other risky behaviors. PMID- 26877747 TI - The Validity and Reliability of Autism Behavior Checklist in Iran. AB - OBJECTIVES: The aim of this study was to evaluate the psychometric features of the Persian version of the Autism Behavior Checklist (ABC). METHOD: The International Quality of Life Assessment (IQOLA) approach was used to translate the English ABC into Persian. A total sample of 184 parents of children including 114 children with autism disorder (mean age =7.21, SD =1.65) and 70 typically developing children (mean age = 6.82, SD =1.75) completed the ABC. Internal consistency, test-retest reliability, concurrent and discriminant validity, and cut-off score were assessed. RESULTS: The results of this study revealed that the Persian version of the ABC has an acceptable degree of internal consistency (.73). Test-retest comparisons using interclass correlation confirmed the instrument's time stability (.83). The instrument's concurrent validity with Gilliam Autism Rating Scale (GARS) was verified; the correlation between total scores was .94. In the discriminant validity, the autism group had significantly higher scores compared to the normal group. Receiver Operating Characteristic (ROC) analysis revealed that individuals with total scores below 25 are less likely to be in the autism group. CONCLUSION: The Persian version of the ABC can be used as an initial screening tool in clinical contexts. PMID- 26877748 TI - Anxiety Assessment in Methamphetamine - Sensitized and Withdrawn Rats: Immediate and Delayed Effects. AB - OBJECTIVE: The anxiety profile in the stimulant-sensitized animals is not clear. Thus, this study was conducted to elucidate the effects of acute and chronic administration of methamphetamine (METH) on the anxiety profile. The aim of this study was to examine whether METH-sensitized rats would show an increase in the expression of anxiogenic-like behaviors and to determine whether a low dose of METH elicits behavioral sensitization. METHODS: Rats were repeatedly given METH (2 mg/kg, s.c., once a day for 14 days), and the immediate and delayed effects of METH on the anxiety profile was compared considering 30 minutes (min) and 120 min after injections in METH-sensitized, withdrawn and intact rats using the elevated plus-maze (EPM), also, to re-challenge with a low dose of METH (0.5 mg/kg) in withdrawn groups. RESULTS: RESULTS have shown that METH-sensitized rats exhibited an increase in the open arm time and entries 120 min after injection compared to the control group. We found a reduction in the time spent in open arms for the immediate effects of METH (30 min after injection) in METH-sensitized rats as compared to the control group. In withdrawn rats, METH/METH groups exhibited an increase in the open arm time and entries than METH/Sal and Sal/METH groups. CONCLUSION: It was found that unlike delayed effects, an immediate effect of METH exhibited anxiogenic-like behaviors in METH-sensitized rats using the EPM. Also, results indicated that a low dose of METH is a potent stimulus for reinstatement of methamphetamine behavioral sensitization in a long withdrawn period. PMID- 26877749 TI - Environmental Psychology Effects on Mental Health Job Satisfaction and Personal Well Being of Nurses. AB - OBJECTIVE: Environmental psychology as a science could be useful in understanding the dissociation between the man and the environment. The aim of this study was to compare mental health, job satisfaction and well-being of nurses who work in hospital environments with different designs. MATERIAL: This was a quasi experimental study, in which 250 nurses filled out the mental health, well-being and job satisfaction questionnaires. They were categorized into 3 groups randomly. Group1 included 63 nurses who worked in an environment without any natural elements; group 2 included 100 nurses who worked in an environment with natural elements and group 3 included 87 nurses who worked in an environment without any psychological and ergonomic design. The last group was only stimulated by demonstrating visual stimulus. Data were analyzed using the ANOVA and Tukey's pursuit statistical method. RESULTS: The nurses who were working in an environment without any natural elements reported significantly lower scores on mental health, well-being and job satisfaction compared to those who were working in other groups, with the exception of social functioning. Moreover, depression and anxiety were more common in nurses who were working in environments without any natural elements compared to those in the other groups (p<0.05). CONCLUSIONS: We can increase job satisfaction, and mental health and well-being of the nurses through the use of natural design and environmental psychology indexes in hospital buildings. PMID- 26877750 TI - Comparison of Sensorimotor Rhythm (SMR) and Beta Training on Selective Attention and Symptoms in Children with Attention Deficit/Hyperactivity Disorder (ADHD): A Trend Report. AB - OBJECTIVE: The aim of this study was to assess and compare the effect of two neurofeedback protocols (SMR/theta and beta/theta) on ADHD symptoms, selective attention and EEG (electroencephalogram) parameters in children with ADHD. METHOD: The sample consisted of 16 children (9-15 year old: 13 boys; 3 girls) with ADHD-combined type (ADHD-C). All of children used methylphenidate (MPH) during the study. The neurofeedback training consisted of two phases of 15 sessions, each lasting 45 minutes. In the first phase, participants were trained to enhance sensorimotor rhythm (12-15 Hz) and reduce theta activity (4-8 Hz) at C4 and in the second phase; they had to increase beta (15-18 Hz) and reduce theta activity at C3. Assessments consisted of d2 attention endurance test, ADHD rating scale (parent form) at three time periods: before, middle and the end of the training. EEG signals were recorded just before and after the training. RESULT: Based on parents' reports, inattention after beta/theta training, and hyperactivity/impulsivity were improved after the end of the training. All subscales of d2 test were improved except for the difference between maximum and minimum responses. However, EEG analysis showed no significant differences. CONCLUSION: Neurofeedback in conjunction with Methylphenidate may cause further improvement in ADHD symptoms reported by parents and selective attention without long-term impact on EEG patterns. However, determining the exact relationship between EEG parameters, neurofeedback protocols and ADHD symptoms remain unclear. PMID- 26877751 TI - Effectiveness of Mindfulness-Based Group Therapy Compared to the Usual Opioid Dependence Treatment. AB - OBJECTIVE: This study investigated the effectiveness of mindfulness-based group therapy (MBGT) compared to the usual opioid dependence treatment (TAU).Thirty outpatients meeting the DSM-IV-TR criteria for opioid dependence from Iranian National Center for Addiction Studies (INCAS) were randomly assigned into experimental (Mindfulness-Based Group Therapy) and control groups (the Usual Treatment).The experimental group undertook eight weeks of intervention, but the control group received the usual treatment according to the INCAS program. METHODS: The Five Factor Mindfulness Questionnaire (FFMQ) and the Addiction Sevier Index (ASI) were administered at pre-treatment and post-treatment assessment periods. Thirteen patients from the experimental group and 15 from the control group completed post-test assessments. RESULTS: The results of MANCOVA revealed an increase in mean scores in observing, describing, acting with awareness, non-judging, non-reacting, and decrease in mean scores of alcohol and opium in MBGT patient group. CONCLUSION: The effectiveness of MBGT, compared to the usual treatment, was discussed in this paper as a selective protocol in the health care setting for substance use disorders. PMID- 26877752 TI - Associated Factors of Suicidal Thoughts in HIV-Positive Individuals. AB - OBJECTIVE: As a first study, suicidal ideation and its correlates have been evaluated in Iranian HIV positive population. METHODS: One hundred and fifty HIV positive individuals were recruited in this cross-sectional study. The Hospital Anxiety and Depression Scale (HADS), Positive and Negative Suicide Ideation (PANSI), Pittsburgh Sleep Quality Inventory (PSQI) and Somatization subscale of Symptom Checklist 90 (SCL 90) as self- reported questionnaires were used to assess the patients' anxiety and depression status, suicidal thoughts, sleep quality and physiological factors, respectively. RESULTS: Antiretroviral therapy and efavirenz intake did not show any significant effects on the patients' suicidal ideation. Anxiety (p<0.001), depression (p<0.001), poor physical activity (P<0.001) and sleep quality (p<0.001) were significantly associated with the patients' negative suicidal ideation. From the patients' demographic data, unemployment (p = 0.04), living alone (p = 0.01), and lack of family support (p = 0.01) were correlated with the patients' negative suicidal thoughts. CONCLUSION: Although hospitals are the main referral centers for providing care for HIV positive individuals in Tehran, Iran, conducting a multi-center study with sufficient sample size from different areas of our country that include individuals with different behaviors and cultures is essential to confirm the results of this study. PMID- 26877755 TI - Bipolar Disorder in a Young Girl with Dandy-Walker Syndrome. PMID- 26877754 TI - Transdiagnostic Treatment of Co-occurrence of Anxiety and Depressive Disorders based on Repetitive Negative Thinking: A Case Series. AB - OBJECTIVE: The transdiagnostic cognitive behavioral treatments for treating the coexistence of anxiety and mood disorders received useful empirical supports in the recent years. However, these treatments still have moderate efficacy. Following the improvements and developments in transdiagnostic protocols and considering the importance of repetitive negative thinking as a core transdiagnostic factor in emotional disorders, this study examined a new form of transdiagnostic treatment based on Repetitive Negative Thinking (TTRNT) of co occurrence of anxiety and depressive disorders. METHODS: Treatment efficacy was assessed using single case series with multiple baselines. Three patients meeting the criteria for co-occurrence of anxiety and depressive disorders were selected using the Anxiety Disorders Interview Schedule for DSM-IV. The patients were treated individually for 12 weekly sessions. Participants completed the standardized outcome measures during the baseline, treatment and one-month follow up. RESULTS: At post-treatment, all participants showed significant clinical changes on a range of standardized outcome measures, and these gains were largely maintained through the one-month follow-up both in the principle and co-principal diagnosis. CONCLUSIONS: Although the results of this preliminary investigation indicated that TTRNT could be a time effective and efficient treatment for individuals with co-occurrence of anxiety and depressive disorders, further controlled clinical trials are necessary to examine this new treatment approach. PMID- 26877753 TI - Effects of Estrogen Receptor Modulators on Morphine Induced Sensitization in Mice Memory. AB - OBJECTIVE: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM) on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task. METHOD: The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline administration. The memory retrieval was evaluated using step down passive avoidance test both on the training and test day. RESULTS: The results illustrated that the three- day administration of morphine induced sensitization through the enhancement of memory retrieval (morphine induced sensitization in mice memory). Both the three- day administration of estradiol valerate alone and with morphine (5 mg/kg) restored memory. On the other hand, the three- day administration of raloxifene had no effect on memory retrieval alone, but declined morphine induced sensitization in mice memory. CONCLUSION: The results of the study indicated that there is an interaction between estrogen receptor modulators and morphine induced sensitization in mice memory. PMID- 26877756 TI - The effect of motion on IMRT - looking at interplay with 3D measurements. AB - Six base of skull IMRT treatment plans were delivered to 3D dosimeters within the RPC Head and Neck Phantom for QA verification. Isotropic 2mm 3D data was obtained using the DLOS-PRESAGE system and compared to an Eclipse (Varian) treatment plan. Normalized Dose Distribution pass rates were obtained for a number of criteria. High quality 3D dosimetry data was observed from the DLOS system, illustrated here through colormaps, isodose lines, profiles, and NDD 3D maps. Excellent agreement with the planned dose distributions was also observed with NDD analysis revealing > 90% NDD pass rates [3%, 2mm], noise < 0.5%. This paper focuses on a detailed exploration of the quality and use of 3D dosimetry data obtained with the DLOS-PRESAGE system. PMID- 26877757 TI - Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states. AB - BACKGROUND: Many people believe in favourable effects of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), especially leucine, on muscle protein balance and consume BCAAs for many years. We determined the effects of the chronic intake of a BCAA- or leucine-enriched diet on protein and amino acid metabolism in fed and postabsorptive states. METHODS: Rats were fed a standard diet, a diet with a high content of valine, leucine, and isoleucine (HVLID), or a high content of leucine (HLD) for 2 months. Half of the animals in each group were sacrificed in the fed state on the last day, and the other half were sacrificed after overnight fast. Protein synthesis was assessed using the flooding dose method (L-[3,4,5-(3)H]phenylalanine), proteolysis on the basis of chymotrypsin-like activity (CHTLA) of proteasome and cathepsin B and L activities. RESULTS: Chronic intake of HVLID or HLD enhanced plasma levels of urea, alanine and glutamine. HVLID also increased levels of all three BCAA and branched-chain keto acids (BCKA), HLD increased leucine, ketoisocaproate and alanine aminotransferase and decreased valine, ketovaline, isoleucine, ketoisoleucine, and LDL cholesterol. Tissue weight and protein content were lower in extensor digitorum longus muscles in the HLD group and higher in kidneys in the HVLID and HLD groups. Muscle protein synthesis in postprandial state was higher in the HVLID group, and CHTLA was lower in muscles of the HVLID and HLD groups compared to controls. Overnight starvation enhanced alanine aminotransferase activity in muscles, and decreased protein synthesis in gastrocnemius (in HVLID group) and extensor digitorum longus (in HLD group) muscles more than in controls. Effect of HVLID and HLD on CHTLA in muscles in postabsorptive state was insignificant. CONCLUSIONS: The results failed to demonstrate positive effects of the chronic consumption of a BCAA-enriched diet on protein balance in skeletal muscle and indicate rather negative effects from a leucine-enriched diet. The primary effects of both diets are an activated catabolism of BCAAs, which leads to an enhanced production of BCKA, alanine and glutamine and their utilization in visceral tissues and an impaired protein synthesis in postabsorptive state, particularly in fast-twitch (white) muscles. PMID- 26877758 TI - Recent advances in management of the HIV/HCV coinfected patient. AB - Chronic hepatitis C virus (HCV) is a global epidemic, affecting approximately 150 million individuals throughout the world. The implications of HCV infection have been magnified in those who are infected with both HCV and the HIV as liver disease progression, liver failure and liver-related death are increased, particularly in those without well-controlled HIV disease. The development of direct-acting antiviral agents for HCV that allow shorter treatment periods with increased efficacy and decreased adverse events have greatly changed the outlook for HCV-infected individuals. With these advancements, growing treatment options for the coinfected population have also come. This review will address pharmacotherapy issues in the HIV/HCV coinfected population. PMID- 26877759 TI - Diagnostic methods for mastitis in cows are not appropriate for use in humans: commentary. AB - Healthcare workers are now being targeted for marketing of diagnostic tools for mastitis that were developed for the dairy industry and which aim to provide information regarding choice of antibiotic treatment. Meanwhile, scientists are striving to understand how the human microbiome affects health and wellbeing and the importance of maintenance of bacterial balance in the human body. Breast milk supplies a multitude of bacteria to populate the baby's intestinal tract and kick start the immune system. Researchers propose a paradigm shift in the understanding of bacterial content in breast milk and an alternative paradigm for the understanding of lactational mastitis: there is the beginning of evidence that many cases of lactational mastitis will resolve spontaneously. An international group of researchers is attempting to answer how dietary habits, birth mode, genetics and environmental factors may impact the bacterial content of breast milk. Until we have more comprehensive knowledge about the human milk microbiome, diagnostic aids for identification of women in need of antibiotic therapy for mastitis remain unreliable. Diagnostic aids could lead to the injudicious use of antibiotic therapy, which in turn may rob the infant of bacteria valuable for development of its immune system. The marketing of diagnostic aids for use in human medicine, that were originally developed for use in cows, is neither evidence-based nor good ethical practice. PMID- 26877760 TI - Aldehyde dehydrogenase isozymes: markers of cancer stem cells in human melanoma. PMID- 26877761 TI - Computational high-resolution optical imaging of the living human retina. AB - High-resolution in vivo imaging is of great importance for the fields of biology and medicine. The introduction of hardware-based adaptive optics (HAO) has pushed the limits of optical imaging, enabling high-resolution near diffraction-limited imaging of previously unresolvable structures1,2. In ophthalmology, when combined with optical coherence tomography, HAO has enabled a detailed three-dimensional visualization of photoreceptor distributions3,4 and individual nerve fibre bundles5 in the living human retina. However, the introduction of HAO hardware and supporting software adds considerable complexity and cost to an imaging system, limiting the number of researchers and medical professionals who could benefit from the technology. Here we demonstrate a fully automated computational approach that enables high-resolution in vivo ophthalmic imaging without the need for HAO. The results demonstrate that computational methods in coherent microscopy are applicable in highly dynamic living systems. PMID- 26877762 TI - Identification of Chinese medicine syndromes in persistent insomnia associated with major depressive disorder: a latent tree analysis. AB - BACKGROUND: Chinese medicine (CM) syndrome (zheng) differentiation is based on the co-occurrence of CM manifestation profiles, such as signs and symptoms, and pulse and tongue features. Insomnia is a symptom that frequently occurs in major depressive disorder despite adequate antidepressant treatment. This study aims to identify co-occurrence patterns in participants with persistent insomnia and major depressive disorder from clinical feature data using latent tree analysis, and to compare the latent variables with relevant CM syndromes. METHODS: One hundred and forty-two participants with persistent insomnia and a history of major depressive disorder completed a standardized checklist (the Chinese Medicine Insomnia Symptom Checklist) specially developed for CM syndrome classification of insomnia. The checklist covers symptoms and signs, including tongue and pulse features. The clinical features assessed by the checklist were analyzed using Lantern software. CM practitioners with relevant experience compared the clinical feature variables under each latent variable with reference to relevant CM syndromes, based on a previous review of CM syndromes. RESULTS: The symptom data were analyzed to build the latent tree model and the model with the highest Bayes information criterion score was regarded as the best model. This model contained 18 latent variables, each of which divided participants into two clusters. Six clusters represented more than 50 % of the sample. The clinical feature co-occurrence patterns of these six clusters were interpreted as the CM syndromes Liver qi stagnation transforming into fire, Liver fire flaming upward, Stomach disharmony, Hyperactivity of fire due to yin deficiency, Heart-kidney noninteraction, and Qi deficiency of the heart and gallbladder. The clinical feature variables that contributed significant cumulative information coverage (at least 95 %) were identified. CONCLUSION: Latent tree model analysis on a sample of depressed participants with insomnia revealed 13 clinical feature co occurrence patterns, four mutual-exclusion patterns, and one pattern with a single clinical feature variable. PMID- 26877763 TI - A novel coumarin, (+)-3'-angeloxyloxy-4'-keto-3',4'-dihydroseselin, isolated from Bupleurum malconense (Chaihu) inhibited NF-kappaB activity. AB - BACKGROUND: This study aims to identify the major anti-inflammatory components in the petroleum ether extract of Bupleurum malconense (Chaihu), by bioassay-guided fractionation, and to investigate the anti-inflammatory mechanisms of active components in lipopolysaccharide (LPS)-stimulated murine macrophage RAW-Blue cells. METHODS: A QUANTI-Blue assay was used to guide fractionation of B. malconense root extract. The petroleum ether extract which exerted significant secreted embryonic alkaline phosphatase (SEAP) inhibition effect was purified by silica gel column chromatography and assisted with reverse phase HPLC. The major bioactive compound which significantly inhibited SEAP activity was obtained and its anti-inflammatory effects in LPS-induced RAW-Blue cells were measured by the overproduction of NO (Griess method), gene expression of Il-1beta, Tnf-alpha and iNos (real-time PCR). In parallel, protein expressions of COX-2, iNOS and IkappaB alpha were determined by western blot. RESULTS: In bioassay-guided fractionation using LPS-stimulated mouse macrophage RAW-Blue cells, (+)-3'-angeloxyloxy-4'-keto 3',4'-dihydroseselin (Pd-Ib) was identified by MS and NMR spectral analyses. Pd Ib (5, 10, 20 MUg/mL) suppressed the gene expression of Il-1beta (P < 0.0001, P < 0.0001, P < 0.0001 for three respective concentrations), Tnf-alpha (P = 0.006, P = 0.001, P < 0.0001 for three respective concentrations) and iNos (P = 0.009, P < 0.0001, P < 0.0001 for three respective concentrations) in LPS-stimulated macrophages. The production of cyclooxygenase-2 (P = 0.019, P = 0.002, P < 0.0001), iNOS (P < 0.0001, P < 0.0001, P < 0.0001 for three respective concentrations) and NO (P < 0.0001, P < 0.0001, P < 0.0001 for three respective concentrations) significantly decreased when macrophages were treated with Pd-Ib (5, 10, 20 MUg/mL) in the presence of LPS. Pd-Ib (5, 10, 20 MUg/mL) suppressed the nuclear activation of NF-kappaB while it up-regulated the IkappaB-alpha level (P = 0.028, P = 0.013, P = 0.005 for three respective concentrations) in LPS stimulated macrophages. CONCLUSIONS: Pd-Ib isolated from B. malconense suppressed LPS-induced inflammatory responses in macrophages by inhibiting NF-kappaB activity and reducing the expression of iNOS, COX-2 as well as pro-inflammatory cytokines. PMID- 26877764 TI - Assessment of central venous catheterization in a simulated model using a motion tracking device: an experimental validation study. AB - BACKGROUND: Central venous catheterization (CVC) is a basic requirement for many medical specialties. Simulated training in CVC may allow the acquisition of this competency but few reports have established a valid methodology for learning and acquiring procedural skills for CVC. This study aims to validate the use of a tracking motion device, the imperial college surgical assessment device (ICSAD), by comparing it with validated global rating scales (GRS) to measure CVC performance in a simulated torso. METHODS: Senior year medical students, first and last year residents (PGY1, LYR), and expert anesthesiologists performed a jugular CVC assessment in a simulated model (Laerdal IV Torso). A validated GRS for objective assessment of technical skills and motion analysis by ICSAD was used. Statistical analysis was performed through Mann-Whitney and Kruskal-Wallis tests for construct validity and Spearman correlation coefficients between the ICSAD and GRS scores for concurrent validity between both. RESULTS: 32 subjects were recruited (10 medical students, 8 PGY1, 8 LYR and 8 experts). Total path length measured with ICSAD and GRS scores were significantly different between all groups, except for LYR compared to experts (p = 0.664 for GRS and p = 0.72 for ICSAD). Regarding jugular CVC procedural time, LYR and experts were faster than PGY1 and MS (p < 0.05). Spearman correlation coefficient was -0.684 (p < 0.001) between ICSAD and GRS scores. CONCLUSIONS: ICSAD is a valid tool for assessment of jugular CVC since it differentiates between expert and novice subjects, and correlates with a validated GRS for jugular CVC in a simulated torso. PMID- 26877765 TI - A Social-Ecological, Process-Oriented Perspective on Political Violence and Child Development. AB - Youths' risk for adjustment problems in contexts of political violence is well documented. However, outcomes vary widely, with many children functioning well. Accordingly, moving beyond further documenting the risk for many negative outcomes associated with living in contexts of political violence, a second generation of research is moving towards identifying the mechanisms and conditions that contribute to children's adjustment. Increasing support is emerging for understanding effects on children in terms of changes in the social contexts in which children live, and in the psychological processes engaged by these social ecologies. Selected themes are considered, including (a) the need to study multiple levels of the social ecology, (b) differentiating between the effects of exposure to contexts of political versus non-political violence, and (c) theories about explanatory processes. Selected research pertinent to these directions is reviewed, including findings from a six-wave longitudinal study on political violence and children in Northern Ireland. PMID- 26877766 TI - A novel efficient beta-glucanase from a paddy soil microbial metagenome with versatile activities. AB - BACKGROUND: Cellulose, an abundant and renewable polysaccharides, constitutes the largest resource for bioconversion of biofuels. Plant polysaccharides hydrolysis is catalyzed by cellulases, which include endoglucanases, exoglucanases, and beta glucosidases. Converting cellulose and hemicellulose to short chains of oligosaccharides by endo-/exoglucanases is the key step for biofuel transformation. Intriguingly, beta-glucanases with transglycosylation activity not only can relieve product inhibition of glucan hydrolysis but also has potential application as biocatalysts for functional materials. RESULTS: Here, a metagenomic fosmid library was constructed from a paddy soil for cellulase screening. One purified clone showing carboxymethylcellulase activity was isolated, and the complete beta-glucanase gene (umcel9y-1) was cloned and overexpressed in Escherichia coli. Phylogenetic analysis indicated that beta glucanase Umcel9y-1 belonged to the theme C of glycoside hydrolase family 9. Amino acids sequence showed 58.4 % similarity between Umcel9y-1 and its closest characterized reference, cellulase Cel01. Biological characterization showed that Umcel9y-1 was an efficient endoglucanase and also exhibited high activities of exoglucanase and transglycosylation. The transglycosylation products of Umcel9y-1 including sophorose, laminaribiose, and gentiobiose, and transglycosylation was detected under all activated conditions. The order of catalytic efficiency for polysaccharides, cellooligosaccharides, and aryl-beta-glycosides was p nitrophenol-D-cellobioside, barley glucan, cellopentaose, cellotetraose, cellotriose, hydroxyethylcellulose, cellohexose, laminarin, and carboxymethylcellulose, respectively. The barley glucan was the optimal polysaccharides for Umcel9y-1 with K m and K cat/K m values of 13.700 mM and 239.152 s(-1) mM(-1), respectively. CONCLUSION: Biological characterizations of recombinant Umcel9y-1 showed that the versatile beta-glucanase had efficient endoglucanase activity to barley glucan and also exhibited high activities of exoglucanase and transglycosylation. The optimum conditions of recombinant Umcel9y-1 was pH 6.5-7.0 at 37 degrees C with predominant halotolerance and high thermal stability. These results indicate that the novel metagenomic-derived beta glucanase may be a potent candidate for industrial applications. PMID- 26877769 TI - Persisting variation in testing and reporting Clostridium difficile cases. AB - Previous evidence suggested a significant variation in the testing algorithms used across the United Kingdom for the diagnosis of Clostridium difficile infection (CDI) and new national guidelines were issued in 2012. The main aim of this paper was to explore if such variation in testing and reporting is still present, to compare the management of CDI cases, and to investigate if there is any significant variation in the antibiotic policies among different hospitals. Using London hospitals as a sample, results show that there is still a wide variation of testing methods and reporting used, making comparisons difficult. It is likely that the overall variability in practices would be greater at a national and, even more, at international level. The relationship between broad spectrum antibiotics and C. difficile incidence and alternative approaches in antibiotic guidelines may require further studies. PMID- 26877768 TI - Why it is crucial to analyze non clonal chromosome aberrations or NCCAs? AB - Current cytogenetics has largely focused its efforts on the identification of recurrent karyotypic alterations, also known as clonal chromosomal aberrations (CCAs). The rationale of doing so seems simple: recurrent genetic changes are relevant for diseases or specific physiological conditions, while non clonal chromosome aberrations (NCCAs) are insignificant genetic background or noise. However, in reality, the vast majority of chromosomal alterations are NCCAs, and it is challenging to identify commonly shared CCAs in most solid tumors. Furthermore, the karyotype, rather than genes, represents the system inheritance, or blueprint, and each NCCA represents an altered genome system. These realizations underscore the importance of the re-evaluation of NCCAs in cytogenetic analyses. In this concept article, we briefly review the definition of NCCAs, some historical misconceptions about them, and why NCCAs are not insignificant "noise," but rather a highly significant feature of the cellular population for providing genome heterogeneity and complexity, representing one important form of fuzzy inheritance. The frequencies of NCCAs also represent an index to measure both internally- and environmentally-induced genome instability. Additionally, the NCCA/CCA cycle is associated with macro- and micro-cellular evolution. Lastly, elevated NCCAs are observed in many disease/illness conditions. Considering all of these factors, we call for the immediate action of studying and reporting NCCAs. Specifically, effort is needed to characterize and compare different types of NCCAs, to define their baseline in various tissues, to develop methods to access mitotic cells, to re-examine/interpret the NCCAs data, and to develop an NCCA database. PMID- 26877770 TI - Whole genome sequencing of "Faecalibaculum rodentium" ALO17, isolated from C57BL/6J laboratory mouse feces. AB - BACKGROUND: Intestinal microorganisms affect host physiology, including ageing. Given the difficulty in controlling for human studies of the gut microbiome, mouse models provide an alternative avenue to study such relationships. In this study, we report on the complete genome of "Faecalibaculum rodentium" ALO17, a bacterium that was isolated from the faeces of a 9-month-old female C57BL/6J mouse. This strain will be utilized in future in vivo studies detailing the relationships between the gut microbiome and ageing. RESULTS: The whole genome sequence of "F. rodentium" ALO17 was obtained using single-molecule, real-time (SMRT) technique on a PacBio instrument. The assembled genome consisted of 2,542,486 base pairs of double-stranded DNA with a GC content of 54.0 % and no plasmids. The genome was predicted to contain 2794 open reading frames, 55 tRNA genes, and 38 rRNA genes. The 16S rRNA gene of ALO17 was 86.9 % similar to that of Allobaculum stercoricanis DSM 13633(T), and the average overall nucleotide identity between strains ALO17 and DSM 13633(T) was 66.8 %. After confirming the phylogenetic relationship between "F. rodentium" ALO17 and A. stercoricanis DSM 13633(T), their whole genome sequences were compared, revealing that "F. rodentium" ALO17 contains more fermentation-related genes than A. stercoricanis DSM 13633(T). Furthermore, "F. rodentium" ALO17 produces higher levels of lactic acid than A. stercoricanis DSM 13633(T) as determined by high-performance liquid chromatography. CONCLUSION: The availability of the "F. rodentium" ALO17 whole genome sequence will enhance studies concerning the gut microbiota and host physiology, especially when investigating the molecular relationships between gut microbiota and ageing. PMID- 26877767 TI - Dipeptidyl peptidase-4 and kidney fibrosis in diabetes. AB - Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease worldwide and is associated with increased morbidity and mortality in patients with both type 1 and type 2 diabetes. Recent evidence revealed that dipeptidyl peptidase-4 (DPP-4) inhibitors may exhibit a protective effect against DN. In fact, the kidney is the organ where the DPP-4 activity is the highest level per organ weight. A preclinical analysis revealed that DPP-4 inhibitors also ameliorated kidney fibrosis. In this review, we analyzed recent reports in this field and explore the renoprotective effects and possible mechanism of the DPP-4 inhibitors. PMID- 26877771 TI - Attribution of extreme weather and climate-related events. AB - Extreme weather and climate-related events occur in a particular place, by definition, infrequently. It is therefore challenging to detect systematic changes in their occurrence given the relative shortness of observational records. However, there is a clear interest from outside the climate science community in the extent to which recent damaging extreme events can be linked to human-induced climate change or natural climate variability. Event attribution studies seek to determine to what extent anthropogenic climate change has altered the probability or magnitude of particular events. They have shown clear evidence for human influence having increased the probability of many extremely warm seasonal temperatures and reduced the probability of extremely cold seasonal temperatures in many parts of the world. The evidence for human influence on the probability of extreme precipitation events, droughts, and storms is more mixed. Although the science of event attribution has developed rapidly in recent years, geographical coverage of events remains patchy and based on the interests and capabilities of individual research groups. The development of operational event attribution would allow a more timely and methodical production of attribution assessments than currently obtained on an ad hoc basis. For event attribution assessments to be most useful, remaining scientific uncertainties need to be robustly assessed and the results clearly communicated. This requires the continuing development of methodologies to assess the reliability of event attribution results and further work to understand the potential utility of event attribution for stakeholder groups and decision makers. WIREs Clim Change 2016, 7:23-41. doi: 10.1002/wcc.380 For further resources related to this article, please visit the WIREs website. PMID- 26877772 TI - Relationship between deep subcutaneous abdominal adipose tissue and metabolic syndrome: a case control study. AB - BACKGROUND: The deep subcutaneous adipose tissue (dSAT) is closely related to the obesity-associated complications similarly to the characteristics of visceral adipose tissue (VAT). However, the association between dSAT and metabolic syndrome (MS) is unclear. The purpose of our study was to evaluate the association of distinct abdominal adipose tissue with the cardiometabolic risk factors and MS. METHODS: Abdominal computed tomography (CT) images were obtained in 365 asymptomatic subjects (187 subjects with MS and 178 without MS). The axial images segmented into superficial and deep SAT by manually tracing the fascia superficialis at L4-5 levels. The concentrations of serum inflammatory cytokines and adipokines were also measured. RESULTS: The MS group had significantly lower adiponectin levels but significantly higher levels of resistin, leptin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), intercellular adhesion molecule (ICAM), monocyte chemotactic protein-1 (MCP-1), and oxLDL than the control group (p < 0.05). All inflammatory cytokines and adipokines were associated with the sum of VAT and dSAT areas (VDAT) (P for trend < 0.05), but no significant correlation was found between inflammatory cytokines and sSAT. dSAT was significantly associated with MS in both men and women (OR 2.371; p < 0.001) whereas the ORs between sSAT and MS were not significant (p = 0.597). The age adjusted ORs between VDAT and MS (OR of 8.359 in men and 3.183 in women, p < 0.001) were higher than those of VAT (OR of 7.941 in men and 2.570 in women, p < 0.05) and dSAT (OR of 2.954 in men and 1.856 in women, p < 0.05). CONCLUSIONS: We demonstrated that dSAT was associated with increased inflammation and oxidative stress, suggesting that dSAT is an important determinant of MS. Therefore, abdominal subcutaneous fat should be considered as two functionally distinct compartments rather than a single entity. PMID- 26877773 TI - Effect of Cichorium intybus L. on the expression of hepatic NF-kappaB and IKKbeta and serum TNF-alpha in STZ- and STZ+ niacinamide-induced diabetes in rats. AB - BACKGROUND: Inflammation is an early event in the development of diabetes type 2 (T2D). Cichorium intybus L. (chicory) possesses anti-inflammatory action. We compared the anti-inflammatory aspect of aqueous chicory seed extract (CSE) in early and late stage T2D in rats. METHODS: Wistar albino rats were divided into nine final groups (n = 6). Three main groups consisted of non-diabetic (Control), early stage diabetes (ET2D; niacinamide/streptozotocin, i.e., NIA/STZ), and late stage diabetes (LT2D; STZ). Within each main group, a subgroup was treated with CSE (125 mg/kg; i.p.); within each diabetic group (STZ and NIA/STZ) a subgroup received metformin (100 mg/kg; i.p.); another subgroup in STZ group received aspirin (120 mg/kg; oral). After 21 days, fasting blood glucose (FBS), insulin, and TNF-alpha level were measured in serum; IKKbeta and NF-kappaB (p65) mRNA and protein expression were evaluated by real time PCR and Western blotting; p65 DNA binding activity was determined by ELISA, in liver tissue. RESULTS: The mRNA and protein expression levels of IKKbeta, and P65 genes increased in both stages of T2D (p < 0.01); CSE decreased their expression (p < 0.001, mRNAs; p < 0.05, proteins). The increased DNA-binding capacity of NF-kappaB (p < 0.0001) in diabetes was lowered by CSE (p < 0.001). The effect of CSE was limited to ET2D requiring insulin. CONCLUSIONS: The anti-inflammatory action of CSE is due to a direct modulation of cytokine expression. The dependency of chicory action on the presence of insulin indicates its usefulness in the early stages of diabetes and for the purpose of preventing and delaying diabetes onset. PMID- 26877774 TI - Evolution Controversy: A Phenomenon Prompted by the Incompatibility between Science and Religious Beliefs. AB - The incompatibility between science and the belief in supernatural causation helps us understand why people do not accept evolution. Belief disrupts, distorts, delays, or stops (3Ds + S) the acceptance of scientific evidence. Here we examine the evolution controversy under three predictions of the incompatibility hypothesis. First, chronological-conflict-and-accommodation, which explains the historical re-emergence of antagonism between evolution and religion when advances in science continue to threaten the belief in supernatural causation; in such situations, creationists' rejection of and subsequent partial acceptance of the new scientific discoveries are expected. Second, change in evolution's acceptance as function of educational attainment, which explains the positive association between acceptance of evolution and level of education. And third, change in evolution's acceptance as function of religiosity, which explains the negative association between acceptance of evolution and level of religious beliefs. We rely on an ample assessment of the attitudes toward evolution by highly-educated audiences (i.e. research faculty, educators of prospective teachers, and college students in the United States) to characterize the associations among the understanding of science and evolution, personal religious convictions, and conservative ideology. We emphasize that harmonious coexistence between science and religion is illusory. If co-persisting in society, their relationship will fluctuate from moderate to intense antagonism. PMID- 26877775 TI - A Fluorescence-Guided Laser Ablation System for Removal of Residual Cancer in a Mouse Model of Soft Tissue Sarcoma. AB - The treatment of soft tissue sarcoma (STS) generally involves tumor excision with a wide margin. Although advances in fluorescence imaging make real-time detection of cancer possible, removal is limited by the precision of the human eye and hand. Here, we describe a novel pulsed Nd:YAG laser ablation system that, when used in conjunction with a previously described molecular imaging system, can identify and ablate cancer in vivo. Mice with primary STS were injected with the protease-activatable probe LUM015 to label tumors. Resected tissues from the mice were then imaged and treated with the laser using the paired fluorescence imaging/ laser ablation device, generating ablation clefts with sub-millimeter precision and minimal underlying tissue damage. Laser ablation was guided by fluorescence to target tumor tissues, avoiding normal structures. The selective ablation of tumor implants in vivo improved recurrence-free survival after tumor resection in a cohort of 14 mice compared to 12 mice that received no ablative therapy. This prototype system has the potential to be modified so that it can be used during surgery to improve recurrence-free survival in patients with cancer. PMID- 26877776 TI - Indocyanine Green Liposomes for Diagnosis and Therapeutic Monitoring of Cerebral Malaria. AB - Cerebral malaria (CM) is a major cause of death of Plasmodium falciparum infection. Misdiagnosis of CM often leads to treatment delay and mortality. Conventional brain imaging technologies are rarely applicable in endemic areas. Here we address the unmet need for a simple, non-invasive imaging methodology for early diagnosis of CM. This study presents the diagnostic and therapeutic monitoring using liposomes containing the FDA-approved fluorescent dye indocyanine green (ICG) in a CM murine model. Increased emission intensity of liposomal ICG was demonstrated in comparison with free ICG. The Liposomal ICG's emission was greater in the brains of the infected mice compared to naive mice and drug treated mice (where CM was prevented). Histological analyses suggest that the accumulation of liposomal ICG in the cerebral vasculature is due to extensive uptake mediated by activated phagocytes. Overall, liposomal ICG offers a valuable diagnostic tool and a biomarker for effectiveness of CM treatment, as well as other diseases that involve inflammation and blood vessel occlusion. PMID- 26877777 TI - Dual Receptor Recognizing Cell Penetrating Peptide for Selective Targeting, Efficient Intratumoral Diffusion and Synthesized Anti-Glioma Therapy. AB - Cell penetrating peptides (CPPs) were widely used for drug delivery to tumor. However, the nonselective in vivo penetration greatly limited the application of CPPs-mediated drug delivery systems. And the treatment of malignant tumors is usually followed by poor prognosis and relapse due to the existence of extravascular core regions of tumor. Thus it is important to endue selective targeting and stronger intratumoral diffusion abilities to CPPs. In this study, an RGD reverse sequence dGR was conjugated to a CPP octa-arginine to form a CendR (R/KXXR/K) motif contained tandem peptide R8-dGR (RRRRRRRRdGR) which could bind to both integrin alphavbeta3 and neuropilin-1 receptors. The dual receptor recognizing peptide R8-dGR displayed increased cellular uptake and efficient penetration ability into glioma spheroids in vitro. The following in vivo studies indicated the active targeting and intratumoral diffusion capabilities of R8-dGR modified liposomes. When paclitaxel was loaded in the liposomes, PTX-R8-dGR-Lip induced the strongest anti-proliferation effect on both tumor cells and cancer stem cells, and inhibited the formation of vasculogenic mimicry channels in vitro. Finally, the R8-dGR liposomal drug delivery system prolonged the medium survival time of intracranial C6 bearing mice by 2.1-fold compared to the untreated group, and achieved an exhaustive anti-glioma therapy including anti tumor cells, anti-vasculogenic mimicry and anti-brain cancer stem cells. To sum up, all the results demonstrated that R8-dGR was an ideal dual receptor recognizing CPP with selective glioma targeting and efficient intratumoral diffusion, which could be further used to equip drug delivery system for effective glioma therapy. PMID- 26877778 TI - Mono-arginine Cholesterol-based Small Lipid Nanoparticles as a Systemic siRNA Delivery Platform for Effective Cancer Therapy. AB - Although efforts have been made to develop a platform carrier for the delivery of RNAi therapeutics, systemic delivery of siRNA has shown only limited success in cancer therapy. Cationic lipid-based nanoparticles have been widely used for this purpose, but their toxicity and undesired liver uptake after systemic injection owing to their cationic surfaces have hampered further clinical translation. This study describes the development of neutral, small lipid nanoparticles (SLNPs) made of a nontoxic cationic cholesterol derivative, as a suitable carrier of systemic siRNA to treat cancers. The cationic cholesterol derivative, mono arginine-cholesterol (MA-Chol), was synthesized by directly attaching an arginine moiety to cholesterol via a cleavable ester bond. siRNA-loaded SLNPs (siRNA@SLNPs) were prepared using MA-Chol and a neutral helper lipid, dioleoyl phosphatidylethanolamine (DOPE), as major components and a small amount of PEGylated phospholipid mixed with siRNA. The resulting nanoparticles were less than ~50 nm in diameter with neutral zeta potential and much lower toxicity than typical cationic cholesterol (DC-Chol)-based lipid nanoparticles. SLNPs loaded with siRNA against kinesin spindle protein (siKSP@SLNPs) exhibited a high level of target gene knockdown in various cancer cell lines, as shown by measurement of KSP mRNA and cell death assays. Furthermore, systemic injection of siKSP@SLNPs into prostate tumor-bearing mice resulted in preferential accumulation of the delivered siRNA at the tumor site and significant inhibition of tumor growth, with little apparent toxicity, as shown by body weight measurements. These results suggest that these SLNPs may provide a systemic delivery platform for RNAi-based cancer therapy. PMID- 26877779 TI - P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3. AB - P-glycoprotein (P-gp) is encoded by the multidrug resistance (MDR1) gene and is well studied as a multi-drug resistance transporter. Peritoneal adhesion formation following abdominal surgery remains an important clinical problem. Here, we found that P-gp was highly expressed in human adhesion fibroblasts and promoted peritoneal adhesion formation in a rodent model. Knockdown of P-gp expression by intraperitoneal injection of MDR1-targeted siRNA significantly reduced both the peritoneal adhesion development rate and adhesion grades. Additionally, we found that operative injury up-regulated P-gp expression in peritoneal fibroblasts through the TGF-beta1/Smad signaling pathway and histone H3 acetylation. The overexpression of P-gp accelerated migration and proliferation of fibroblasts via volume-activated Cl(-) current and cell volume regulation by enhancing phosphorylation of the chloride channel-3. Therefore, P gp plays a critical role in postoperative peritoneal adhesion formation and may be a valuable therapeutic target for preventing the formation of peritoneal adhesions. PMID- 26877780 TI - BET Bromodomain Inhibition as a Therapeutic Strategy in Ovarian Cancer by Downregulating FoxM1. AB - Ovarian cancer is responsible for the highest mortality among all gynecologic malignancies, and novel therapies are urgently needed to improve patient outcome. Here we performed an integrative genomic analysis and identified the bromodomain and extraterminal domain (BET) protein BRD4 as a potential therapeutic target in ovarian cancer. Suppression of BRD4 using small-molecule BET inhibitors JQ1 and I BET151, or dual kinase-bromodomain inhibitor volasertib, led to robust and broad antitumor effects across all subclasses of ovarian cancer. In contrast to many other cancers which are susceptible to BET inhibition due to downregulation of super-enhancer-dependent MYC transcript, we discovered that JQ1-sensitive ovarian cancer cells exhibited marked disruption of Forkhead box protein M1 (FoxM1) pathway, a key driver of ovarian carcinoma. These in vitro findings were further supported by in vivo efficacies of JQ1 targeting both cell line-based and patient derived xenograft models. Our data establish a new treatment strategy against ovarian cancer by employing epigenetic vulnerabilities, and provide a mechanistic rationale for the clinical investigation of BET bromodomain inhibitors in this deadly disease. PMID- 26877781 TI - Smartphone-Based Fluorescent Diagnostic System for Highly Pathogenic H5N1 Viruses. AB - Field diagnostic tools for avian influenza (AI) are indispensable for the prevention and controlled management of highly pathogenic AI-related diseases. More accurate, faster and networked on-site monitoring is demanded to detect such AI viruses with high sensitivity as well as to maintain up-to-date information about their geographical transmission. In this work, we assessed the clinical and field-level performance of a smartphone-based fluorescent diagnostic device with an efficient reflective light collection module using a coumarin-derived dendrimer-based fluorescent lateral flow immunoassay. By application of an optimized bioconjugate, a smartphone-based diagnostic device had a two-fold higher detectability as compared to that of the table-top fluorescence strip reader for three different AI subtypes (H5N3, H7N1, and H9N2). Additionally, in a clinical study of H5N1-confirmed patients, the smartphone-based diagnostic device showed a sensitivity of 96.55% (28/29) [95% confidence interval (CI): 82.24 to 99.91] and a specificity of 98.55% (68/69) (95% CI: 92.19 to 99.96). The measurement results from the distributed individual smartphones were wirelessly transmitted via short messaging service and collected by a centralized database system for further information processing and data mining. Smartphone-based diagnosis provided highly sensitive measurement results for H5N1 detection within 15 minutes. Because of its high sensitivity, portability and automatic reporting feature, the proposed device will enable agile identification of patients and efficient control of AI dissemination. PMID- 26877783 TI - 11C-Methionine-PET in Multiple Myeloma: Correlation with Clinical Parameters and Bone Marrow Involvement. AB - Multiple myeloma (MM) remains an essentially incurable hematologic malignancy originating from clonal plasma cells. This study evaluated the usefulness of the radiotracers (11)C-methionine (MET) and (18)F-2'-deoxy-2'-fluorodeoxyglucose (FDG) for staging and re-staging in MM. 43 patients with MM underwent both MET- and FDG-PET/CT for staging or re-staging within 3+/-2 days. Scans were compared on a patient and on a lesion basis. Tracer uptake was correlated with the degree of bone marrow (BM) involvement and standard clinical parameters of disease activity. Additionally, BM samples were stained for L-type amino acid transporter 1 (LAT1) expression in 15 patients. MET-PET detected focal lesions (FL) in 39/43 subjects (90.7%), whereas 10 patients were missed in FDG-PET/CT (detection rate, 33/43; 76.7%; p<0.05). MET depicted more FL in 28/43 patients (65.1%; p<0.001), whereas in the remainder (34.9%, n=15) both tracers yielded comparable results. LAT1 was highly expressed on the cell surface of myeloma cells. Both FDG and MET uptake correlated significantly with biopsy-proven BM involvement (p<0.001), with MET demonstrating a stronger correlation (SUVmean, r=0.9 vs r=0.6; SUVmax, r=0.88 vs r=0.58). Abnormal beta-2-microglobulin and free light chain levels correlated with the presence of focal intramedullary lesions detected in MET- or FDG-PET/CT (MET, p=0.006 and p=0.01, respectively; FDG, p=0.02 and p=0.01). MET appears to be superior to FDG for staging and re-staging of both intra- and extramedullary MM lesions. Tracer uptake correlates with BM involvement, beta2m and FLC levels and appears to be a more accurate marker of tumor burden and disease activity. PMID- 26877782 TI - Chemical Conjugation of Evans Blue Derivative: A Strategy to Develop Long-Acting Therapeutics through Albumin Binding. AB - The efficacy of therapeutic drugs is highly dependent on their optimal in vivo pharmacokinetics. Albumin conjugation is considered to be one of the most effective means of protracting the short lifespan of peptides and proteins. In this study, we proposed a novel platform for developing long lasting therapeutics by conjugating a small molecular albumin binding moiety, truncated Evans blue, to either peptides or proteins. Using the anti-diabetic peptide drug Exendin-4 as a model peptide, we synthesized a new long-acting Exendin-4 derivative (denoted as Abextide). Through complexation with albumin in situ, the biological half-life of Abextide was significantly extended. The hypoglycemic effect of Abextide was also improved remarkably over Exendin-4. Thus, Abextide has considerable potential to treat type 2 diabetes. This strategy as a general technology platform can be applied to other small molecules and biologics for the development of long-acting therapeutic drugs. PMID- 26877784 TI - Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY 025 Affibody PET/CT. AB - PURPOSE: Positron Emission Tomography (PET) imaging of HER2 expression could potentially be used to select patients for HER2-targed therapy, predict response based on uptake and be used for monitoring. In this phase I/II study the HER2 binding Affibody molecule ABY-025 was labeled with (68)Ga-gallium ([(68)Ga]ABY 025) for PET to study effect of peptide mass, test-retest variability and correlation of quantified uptake in tumors to histopathology. EXPERIMENTAL DESIGN: Sixteen women with known metastatic breast cancer and on-going treatment were included and underwent FDG PET/CT to identify viable metastases. After iv injection of 212+/-46 MBq [(68)Ga]ABY-025 whole-body PET was performed at 1, 2 and 4 h. In the first 10 patients (6 with HER2-positive and 4 with HER2-negative primary tumors), [(68)Ga]ABY-025 PET/CT with two different doses of injected peptide was performed one week apart. In the last six patients (5 HER2-positive and 1 HER2-negative primary tumors), repeated [(68)Ga]ABY-025 PET were performed one week apart as a test-retest of uptake in individual lesions. Biopsies from 16 metastases in 12 patients were collected for verification of HER2 expression by immunohistochemistry and in-situ hybridization. RESULTS: Imaging 4h after injection with high peptide content discriminated HER2-positive metastases best (p<0.01). PET SUV correlated with biopsy HER2-scores (r=0.91, p<0.001). Uptake was five times higher in HER2-positive than in HER2-negative lesions with no overlap (p=0.005). The test-retest intra-class correlation was r=0.996. [(68)Ga]ABY-025 PET correctly identified conversion and mixed expression of HER2 and targeted treatment was changed in 3 of the 16 patients. CONCLUSION: [(68)Ga]ABY-025 PET accurately quantifies whole-body HER2-receptor status in metastatic breast cancer. PMID- 26877785 TI - In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles. AB - AIMS: This study aims to explore non-invasive imaging of atherosclerotic plaque through magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) by using profilin-1 targeted magnetic iron oxide nanoparticles (PF1-Cy5.5-DMSA-Fe3O4 NPs, denoted as PC-NPs) as multimodality molecular imaging probe in murine model of atherosclerosis. METHODS AND RESULTS: PC-NPs were constructed by conjugating polyclonal profilin-1 antibody and NHS-Cy5.5 fluorescent dye to the surface of DMSA-Fe3O4-nanoparticles via condensation reaction. Murine atherosclerosis model was induced in apoE(-/-) mice by high fat and cholesterol diet (HFD) for 16 weeks. The plaque areas in aortic artery were detected with Oil Red O staining. Immunofluorescent staining and Western blot analysis were applied respectively to investigate profilin-1 expression. CCK-8 assay and transwell migration experiment were performed to detect vascular smooth muscle cells (VSMCs) proliferation. In vivo MRI and NIRF imaging of atherosclerotic plaque were carried out before and 36 h after intravenous injection of PC-NPs. Oil Red O staining showed that the plaque area was significantly increased in HFD group (p<0.05). Immunofluorescence staining revealed that profilin-1 protein was highly abundant within plaque in HFD group and co-localized with alpha-smooth muscle actin. Profilin-1 siRNA intervention could inhibit VSMCs proliferation and migration elicited by ox-LDL (p<0.05). In vivo MRI and NIRF imaging revealed that PC-NPs accumulated in atherosclerotic plaque of carotid artery. There was a good correlation between the signals of MRI and ex vivo fluorescence intensities of NIRF imaging in animals with PC-NPs injection. CONCLUSION: PC-NPs is a promising dual modality imaging probe, which may improve molecular diagnosis of plaque characteristics and evaluation of pharmaceutical interventions for atherosclerosis. PMID- 26877787 TI - Response to Intervention. AB - The purpose of this interdisciplinary paper is to describe Response to Intervention (RTI), or multi-tier systems of support, for early literacy to improve reading outcomes for students with or at risk for reading disability. First we review the current US policy on RTI for the purpose of early literacy intervention and for identification of reading disabilities. We situate this within recent efforts in developing countries supported by the World Bank and the Early Grade Reading Assessments. Then, we highlight a large experimental study we conducted with first graders and provide findings from a third grade follow up. We conclude with implications for research, practice, and policy. PMID- 26877788 TI - Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane. AB - Palladium catalysed carbonylation reactions using the meta- and para-iodo derivatives of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4) are illustrated as the start point for a variety of functional group interconversions. The resultant benzaldehyde and benzoic acids offer novel building blocks for further derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. PMID- 26877786 TI - New Perspectives Offered by Nuclear Medicine for the Imaging and Therapy of Multiple Myeloma. AB - The management of multiple myeloma has fundamentally changed over the years and imaging techniques able to match the therapeutic advances are now much needed. Although many patients now achieve complete response after first-line treatment, relapse is common. Therefore, it would be important to improve the initial prognostic stratification and to detect minimal residual disease after treatment. (18)F-FDG-PET/CT is a useful imaging tool which has a high prognostic value at baseline evaluation and can effectively differentiate active from inactive lesions during induction treatment or after autologous stem-cell transplantation. In combination with biological data, it improves the prediction of relapse. Other PET tracers may soon enter clinical practice and overcome some of the limitations of (18)F-FDG, such as the low sensitivity in detecting early bone marrow infiltration. Excellent results with (11)C-Methionine are reported by Lapa and colleagues in this issue of the Journal. (11)C-Methionine uptake reflects the increased protein synthesis of malignant plasmocytes and correlates well with bone marrow infiltration. Other promising PET ligands include lipid tracers, such as (11)C-Choline or (11)C-acetate, and some peptide tracers, such as (68)Ga Pentixafor, that targets CXCR4 (chemokine receptor-4), which is often expressed with high density by myeloma cells. Malignant plasma cells are radiosensitive and thus potentially amenable to systemic radionuclide therapy. Indeed, excellent preclinical results were obtained with radioimmunotherapy targeting CD38. Also, preliminary clinical results with peptides targeting CXCR4 (e.g. (177)Lu- or (90)Y-Pentixather) are encouraging. Multiple myeloma may represent a renewal of the already strong partnership between hematologists and nuclear medicine physicians. PMID- 26877789 TI - Synthesis and photophysical characteristics of polyfluorene polyrotaxanes. AB - Two alternating polyfluorene polyrotaxanes (3.TM-betaCD and 3.TM-gammaCD) have been synthesized by the coupling of 2,7-dibromofluorene encapsulated into 2,3,6 tri-O-methyl-beta- or gamma-cyclodextrin (TM-betaCD, TM-gammaCD) cavities with 9,9-dioctylfluorene-2,7-diboronic acid bis(1,3-propanediol) ester. Their optical, electrochemical and morphological properties have been evaluated and compared to those of the non-rotaxane counterpart 3. The influence of TM-betaCD or TM-gammaCD encapsulation on the thermal stability, solubility in common organic solvents, film forming ability was also investigated. Polyrotaxane 3.TM-betaCD exhibits a hypsochromic shift, while 3.TM-gammaCD displays a bathochromic with respect to the non-rotaxane 3 counterpart. For the diluted CHCl3 solutions the fluorescence lifetimes of all compounds follow a mono-exponential decay with a time constant of ~0.6 ns. At higher concentration the fluorescence decay remains mono exponential for 3.TM-betaCD and polymers 3, with a lifetime tau = 0.7 ns and 0.8 ns, whereas the 3.TM-gammaCD polyrotaxane shows a bi-exponential decay consisting of a main component (with a weight of 98% of the total luminescence) with a relatively short decay constant of tau1 = 0.7 ns and a minor component with a longer lifetime of tau2 = 5.4 ns (2%). The electrochemical band gap (DeltaE g ) of 3.TM-betaCD polyrotaxane is smaller than that of 3.TM-gammaCD and 3, respectively. The lower DeltaE g value for 3.TM-betaCD suggests that the encapsulation has a greater effect on the reduction process, which affects the LUMO energy level value. Based on AFM analysis, 3.TM-betaCD and 3.TM-gammaCD polyrotaxane compounds exhibit a granular morphology with lower dispersity and smaller roughness exponent of the film surfaces in comparison with those of the neat copolymer 3. PMID- 26877790 TI - Synthesis of cyclic N (1)-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells. AB - Cyclic N (1)-pentylinosine monophosphate (cpIMP), a novel simplified inosine derivative of cyclic ADP-ribose (cADPR) in which the N (1)-pentyl chain and the monophosphate group replace the northern ribose and the pyrophosphate moieties, respectively, was synthesized. The role played by the position of the phosphate group in the key cyclization step, which consists in the formation of a phosphodiester bond, was thoroughly investigated. We have also examined the influence of the phosphate bridge on the ability of cpIMP to mobilize Ca(2+) in PC12 neuronal cells in comparison with the pyrophosphate bridge present in the cyclic N (1)-pentylinosine diphosphate analogue (cpIDP) previously synthesized in our laboratories. The preliminary biological tests indicated that cpIMP and cpIDP induce a rapid increase of intracellular Ca(2+) concentration in PC12 neuronal cells. PMID- 26877791 TI - Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions. AB - The development of enantioselective, copper-catalyzed alkynylations of cyclic iminium and oxocarbenium ions is reviewed. The use of chiral copper-based catalysts has enabled high yields and enantioselectivites in the formation of nitrogen- and oxygen-containing heterocycles with alpha-stereogenic centers. This review highlights both the accomplishments and the future work needed in this important area. PMID- 26877792 TI - Genicunolide A, B and C: three new triterpenoids from Euphorbia geniculata. AB - Three new triterpenoids, designated as genicunolide A (1), B (2) and C (3), along with friedelin (4) and friedelinol (5), were isolated from the aerial parts of Euphorbia geniculata. They were characterized as 1beta-acetoxy-3beta-hydroxy 11alpha,12alpha-oxidotaraxer-14-ene, 1beta,3beta-diacetoxy-21alpha-hydroxy 11alpha,12alpha-oxidotaraxer-14-ene and 3beta,9alpha,20alpha-trihydroxy-Psi taraxast-5-ene, respectively, by spectral and chemical methods. PMID- 26877793 TI - Learning from the unexpected in life and DNA self-assembly. AB - The greatest lessons in life and science often arise from the unexpected. Thus, rather than viewing these experiences as hindering our progress, they should be embraced and appreciated for their ability to lead to new discoveries. In this perspective, I will discuss the unexpected events that have shaped my career path and the early stages of my independent research program. PMID- 26877794 TI - Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives. AB - A copper-catalyzed aminooxygenation reaction of styrenes with N fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives has been developed. The aminooxygenation product could be converted into the corresponding alcohol or free amine through the cleavage of the N-O or C-N bond of the N hydroxyphthalimide moiety. PMID- 26877795 TI - Direct estimate of the internal pi-donation to the carbene centre within N heterocyclic carbenes and related molecules. AB - Fifteen cyclic and acylic carbenes have been calculated with density functional theory at the BP86/def2-TZVPP level. The strength of the internal X->p(pi) pi donation of heteroatoms and carbon which are bonded to the C(II) atom is estimated with the help of NBO calculations and with an energy decomposition analysis. The investigated molecules include N-heterocyclic carbenes (NHCs), the cyclic alkyl(amino)carbene (cAAC), mesoionic carbenes and ylide-stabilized carbenes. The bonding analysis suggests that the carbene centre in cAAC and in diamidocarbene have the weakest X->p(pi) pi-donation while mesoionic carbenes possess the strongest pi-donation. PMID- 26877797 TI - Recent advances in metathesis-derived polymers containing transition metals in the side chain. AB - This account critically surveys the field of side-chain transition metal containing polymers as prepared by controlled living ring-opening metathesis polymerization (ROMP) of the respective metal-incorporating monomers. Ferrocene- and other metallocene-modified polymers, macromolecules including metal-carbonyl complexes, polymers tethering early or late transition metal complexes, etc. are herein discussed. Recent advances in the design and syntheses reported mainly during the last three years are highlighted, with special emphasis on new trends for superior applications of these hybrid materials. PMID- 26877796 TI - Pyridylidene ligand facilitates gold-catalyzed oxidative C-H arylation of heterocycles. AB - Triaryl-2-pyridylidene effectively facilitates the gold-catalyzed oxidative C-H arylation of heteroarenes with arylsilanes as a unique electron-donating ligand on gold. The employment of the 2-pyridylidene ligand, which is one of the strongest electron-donating N-heterocyclic carbenes, resulted in the rate acceleration of the C-H arylation reaction of heterocycles over conventional ligands such as triphenylphosphine and a classical N-heterocyclic carbene. In situ observation and isolation of the 2-pyridylidene-gold(III) species, as well as a DFT study, indicated unusual stability of gold(III) species stabilized by strong electron donation from the 2-pyridylidene ligand. Thus, the gold(I)-to gold(III) oxidation process is thought to be facilitated by the highly electron donating 2-pyridylidene ligand. PMID- 26877798 TI - Physical properties and biological activities of hesperetin and naringenin in complex with methylated beta-cyclodextrin. AB - The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with beta cyclodextrin (beta-CD) and its methylated derivatives (2,6-di-O-methyl-beta cyclodextrin, DM-beta-CD and randomly methylated-beta-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (beta-CD and DM-beta-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM beta-CD. The vdW force is the main guest-host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-beta-CD/DM-beta-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated beta-CDs. PMID- 26877799 TI - Bright molecules for sensing, computing and imaging: a tale of two once-troubled cities. AB - The circumstances in Colombo, Sri Lanka, and in Belfast, Northern Ireland, which led to a) the generalization of luminescent PET (photoinduced electron transfer) sensing/switching as a design tool, b) the construction of a market-leading blood electrolyte analyzer and c) the invention of molecular logic-based computation as an experimental field, are delineated. Efforts to extend the philosophy of these approaches into issues of small object identification, nanometric mapping, animal visual perception and visual art are also outlined. PMID- 26877800 TI - Polydisperse methyl beta-cyclodextrin-epichlorohydrin polymers: variable contact time (13)C CP-MAS solid-state NMR characterization. AB - The polymerization of partially methylated beta-cyclodextrin (CRYSMEB) with epichlorohydrin was carried out in the presence of a known amount of toluene as imprinting agent. Three different preparations (D1, D2 and D3) of imprinted polymers were obtained and characterized by solid-state (13)C NMR spectroscopy under cross-polarization magic angle spinning (CP-MAS) conditions. The polymers were prepared by using the same synthetic conditions but with different molar ratios of imprinting agent/monomer, leading to morphologically equivalent materials but with different absorption properties. The main purpose of the work was to find a suitable spectroscopic descriptor accounting for the different imprinting process in three homogeneous polymeric networks. The polymers were characterized by studying the kinetics of the cross-polarization process. This approach is based on variable contact time CP-MAS spectra, referred to as VCP MAS. The analysis of the VCP-MAS spectra provided two relaxation parameters: T CH (the CP time constant) and T 1rho (the proton spin-lattice relaxation time in the rotating frame). The results and the analysis presented in the paper pointed out that T CH is sensitive to the imprinting process, showing variations related to the toluene/cyclodextrin molar ratio used for the preparation of the materials. Conversely, the observed values of T 1rho did not show dramatic variations with the imprinting protocol, but rather confirmed that the three polymers are morphologically similar. Thus the combined use of T CH and T 1rho can be helpful for the characterization and fine tuning of imprinted polymeric matrices. PMID- 26877801 TI - New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand. AB - The synthesis of a new type of Hoveyda-Grubbs 2(nd) generation catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient alpha,beta-unsaturated compounds even at 0 degrees C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. PMID- 26877802 TI - A convergent, umpoled synthesis of 2-(1-amidoalkyl)pyridines. AB - A convenient, one-pot, two-component synthesis of 2-(1-amidoalkyl)pyridines is reported, based upon the substitution of suitably-activated pyridine N-oxides by azlactone nucleophiles, followed by decarboxylative azlactone ring-opening. The synthesis obviates the need for precious metal catalysts to achieve a formal enolate arylation reaction, and constitutes a formally 'umpoled' approach to this valuable class of bioactive structures. PMID- 26877803 TI - Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports. AB - An ammonium-tagged ruthenium complex, 8, was deposited on several widely available commercial solid materials such as silica gel, alumina, cotton, filter paper, iron powder or palladium on carbon. The resulting catalysts were tested in toluene or ethyl acetate, and found to afford metathesis products in high yield and with extremely low ruthenium contamination. Depending on the support used, immobilised catalyst 8 shows also additional traits, such as the possibility of being magnetically separated or the use for metathesis and subsequent reduction of the obtained double bond in one pot. PMID- 26877804 TI - Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho hydroxychalcones and 2-bromoallyl sulfones. AB - The cesium carbonate-mediated reaction of 2-bromoallyl sulfones and ortho hydroxychalcones furnished 3-arylsulfonyl-4H-chromene derivatives in 58-67% yield (18 examples). 2-Bromoallyl sulfones functioned as synthetic surrogates for allenyl sulfones in the reaction. PMID- 26877805 TI - Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines. AB - This paper reports a novel approach for the direct and facile synthesis of 1,2 oxyamino moieties via an intermolecular copper-catalyzed oxyamination of olefins. This strategy utilizes O-benzoylhydroxylamines as an electrophilic amine source and carboxylic acids as a nucleophilic oxygen source to achieve a modular difunctionalization of olefins. The reaction proceeded in a regioselective manner with moderate to good yields, exhibiting a broad scope of carboxylic acid, amine, and olefin substrates. PMID- 26877806 TI - Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol. AB - Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV-visible competitive method, phase solubility studies as well as (1)H and DOSY (1)H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food. PMID- 26877807 TI - Solving the puzzling competition of the thermal C(2)-C(6) vs Myers-Saito cyclization of enyne-carbodiimides. AB - The mechanism of the thermal cyclization of enyne-carbodiimides 7a-c has been studied computationally by applying the DFT method. The results indicate that enyne-carbodiimides preferentially follow the C(2)-C(6) (Schmittel) cyclization pathway in a concerted fashion although the Myers-Saito diradical formation is kinetically preferred. The experimentally verified preference of the C(2)-C(6) over the Myers-Saito pathway is guided by the inability of the Myers-Saito diradical to kinetically compete in the rate-determining trapping reactions, either inter- or intramolecular, with the concerted C(2)-C(6) cyclization. As demonstrated with enyne-carbodiimide 11, the Myers-Saito channel can be made the preferred pathway if the trapping reaction by hydrogen transfer is no more rate determining. PMID- 26877808 TI - Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host-guest complexation. AB - The employment of cyclodextrin host-guest complexation to construct supramolecular assemblies with an emphasis on polymer networks is reviewed. The main driving force for this supramolecular assembly is host-guest complexation between cyclodextrin hosts and guest groups either of which may be discrete molecular species or substituents on a polymer backbone. The effects of such complexation on properties at the molecular and macroscopic levels are discussed. It is shown that cyclodextrin complexation may be used to design functional polymer materials with tailorable properties, especially for photo-, pH-, thermo- and redox-responsiveness and self-healing. PMID- 26877809 TI - Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies. AB - Chemically modified cyclodextrins carrying both hydrophobic and hydrophilic substituents may form supramolecular aggregates or nanostructures of great interest. These systems have been usually investigated and characterized in water for their potential use as nanocarriers for drug delivery, but they can also aggregate in apolar solvents, as shown in the present paper through atomistic molecular dynamics simulations and dynamic light scattering measurements. The simulations, carried out with a large number of molecules in vacuo adopting an unbiased bottom-up approach, suggest the formation of bidimensional structures with characteristic length scales of the order of 10 nm, although some of these sizes are possibly affected by the assumed periodicity of the simulation cell, in particular at longer lengths. In any case, these nanostructures are stable at least from the kinetic viewpoint for relatively long times thanks to the large number of intermolecular interactions of dipolar and dispersive nature. The dynamic light scattering experiments indicate the presence of aggregates with a hydrodynamic radius of the order of 80 nm and a relatively modest polydispersity, even though smaller nanometer-sized aggregates cannot be fully ruled out. Taken together, these simulation and experimental results indicate that amphiphilically modified cyclodextrins do also form large-scale nanoaggregates even in apolar solvents. PMID- 26877810 TI - N-Methylphthalimide-substituted benzimidazolium salts and PEPPSI Pd-NHC complexes: synthesis, characterization and catalytic activity in carbon-carbon bond-forming reactions. AB - A series of novel benzimidazolium salts (1-4) and their pyridine enhanced precatalyst preparation stabilization and initiation (PEPPSI) themed palladium N heterocyclic carbene complexes [PdCl2(NHC)(Py)] (5-8), where NHC = 1-(N methylphthalimide)-3-alkylbenzimidazolin-2-ylidene and Py = 3-chloropyridine, were synthesized and characterized by means of (1)H and (13)C{(1)H} NMR, UV-vis (for 5-8), ESI-FTICR-MS (for 2, 4, 6-8) and FTIR spectroscopic methods and elemental analysis. The synthesized compounds were tested in Suzuki-Miyaura cross coupling (for 1-8) and arylation (for 5-8) reactions. As catalysts, they demonstrated a highly efficient route for the formation of asymmetric biaryl compounds even though they were used in very low loading. For example, all compounds displayed good catalytic activity for the C-C bond formation of 4-tert butylphenylboronic acid with 4-chlorotoluene. PMID- 26877811 TI - Hydroquinone-pyrrole dyads with varied linkers. AB - A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C=C) has been synthesized. Their electronic properties have been deduced from (1)H NMR, (13)C NMR, and UV-vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO-LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices. PMID- 26877812 TI - Supramolecular structures based on regioisomers of cinnamyl-alpha-cyclodextrins - new media for capillary separation techniques. AB - This work focuses on the preparation and application of supramolecular structures based on mono-cinnamyl-alpha-cyclodextrins (Cin-alpha-CD). Pure regioisomers of Cin-alpha-CD having the cinnamyl moiety at the 2-O- or at the 3-O-position, respectively, were prepared, characterized and applied in capillary electrophoresis as additives to the background electrolyte. These new monomer units with a potential to self-organize into supramolecular structures were synthesized via a straightforward one-step synthetic procedure and purified using preparative reversed-phase chromatography allowing a large scale separation of the regioisomers. The ability of the monomers to self-assemble was proved by various methods including NMR spectroscopy and dynamic light scattering (DLS). The light scattering experiments showed that the monomer units have distinguishable ability to form supramolecular structures in different solvents and the size distribution of the aggregates in water can be easily modulated using different external stimuli, such as temperature or competitive guest molecules. The obtained results indicated that the two regioisomers of Cin-alpha CD formed different supramolecular assemblies highlighting the fact that the position of the cinnamyl group plays an important role in the intermolecular complex formation. PMID- 26877813 TI - Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes. AB - Oxidation of 3- and 4-pentafluorosulfanyl-substituted anisoles and phenols with hydrogen peroxide and sulfuric acid provided a mixture of SF5-substituted muconolactone, maleic, and succinic acids. A plausible mechanism for the formation of the aliphatic SF5 compounds was presented and their chemical reactivity was investigated. SF5-substituted para-benzoquinone was synthesized; its oxidation led to an improved yield of 2-(pentafluorosulfanyl)maleic acid. The reaction of SF5-substituted maleic anhydride and para-benzoquinone with cyclopentadiene afforded the Diels-Alder adducts. Decomposition of 3 (pentafluorosulfanyl)muconolactone in acidic, neutral and basic aqueous media was investigated and the decarboxylation of 2-(pentafluorosulfanyl)maleic acid provided 3-(pentafluorosulfanyl)acrylic acid. PMID- 26877814 TI - Versatile deprotonated NHC: C,N-bridged dinuclear iridium and rhodium complexes. AB - Bearing the versatility of N-heterocyclic carbene (NHC) ligands, here density functional theory (DFT) calculations unravel the capacity of coordination of a deprotonated NHC ligand (pNHC) to generate a doubly C2,N3-bridged dinuclear complex. Here, in particular the discussion is based on the combination of the deprotonated 1-arylimidazol (aryl = mesityl (Mes)) with [M(cod)(MU-Cl)] (M = Ir, Rh) generated two geometrical isomers of complex [M(cod){u-C3H2N2(Mes) kappaC2,kappaN3}]2). The latter two isomers display conformations head-to-head (H H) and head-to-tail (H-T) of C S and C 2 symmetry, respectively. The isomerization from the H-H to the H-T conformation is feasible, whereas next substitutions of the cod ligand by CO first, and PMe3 later confirm the H-T coordination as the thermodynamically preferred. It is envisaged the exchange of the metal, from iridium to rhodium, confirming here the innocence of the nature of the metal for such arrangements of the bridging ligands. PMID- 26877816 TI - Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction. AB - Enantiomerically pure beta-aminoalcohols, produced through an organocatalytic Mannich reaction, were subjected to an Ugi multicomponent reaction under classical or Lewis acid-promoted conditions with diastereoselectivities ranging from moderate to good. This approach represents a step-economical path to enantiomerically pure, polyfunctionalized peptidomimetics endowed with three stereogenic centers, allowing the introduction of five diversity inputs. PMID- 26877815 TI - A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy. AB - This review summarizes part of the author's research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples. PMID- 26877817 TI - Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen. AB - The methylene group of various substituted 2- and 4-benzylpyridines, benzyldiazines and benzyl(iso)quinolines was successfully oxidized to the corresponding benzylic ketones using a copper or iron catalyst and molecular oxygen as the stoichiometric oxidant. Application of the protocol in API synthesis is exemplified by the alternative synthesis of a precursor to the antimalarial drug Mefloquine. The oxidation method can also be used to prepare metabolites of APIs which is illustrated for the natural product papaverine. ICP MS analysis of the purified reaction products revealed that the base metal impurity was well below the regulatory limit. PMID- 26877819 TI - Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio discrimination agents in asymmetric allylic alkylation. AB - In the present work, we describe a convenient synthesis of spiro-fused D-fructo- and D-psico-configurated oxazoline ligands and their application in asymmetric catalysis. The ligands were synthesized from readily available 3,4,5-tri-O-benzyl 1,2-O-isopropylidene-beta-D-fructopyranose and 3,4,5-tri-O-benzyl-1,2-O isopropylidene-beta-D-psicopyranose, respectively. The latter compounds were partially deprotected under acidic conditions followed by condensation with thiocyanic acid to give an anomeric mixture of the corresponding 1,3-oxazolidine 2-thiones. The anomeric 1,3-oxazolidine-2-thiones were separated after successive benzylation, fully characterized and subjected to palladium catalyzed Suzuki Miyaura coupling with 2-pyridineboronic acid N-phenyldiethanolamine ester to give the corresponding 2-pyridyl spiro-oxazoline (PyOx) ligands. The spiro-oxazoline ligands showed high asymmetric induction (up to 93% ee) when applied as chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R) enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess. PMID- 26877818 TI - Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8 quinolinolate co-ligands. AB - A straightforward synthesis utilizing the ring-opening metathesis polymerization (ROMP) reaction is described for acid-triggered N,O-chelating ruthenium-based pre catalysts bearing one or two 8-quinolinolate ligands. The innovative pre catalysts were tested regarding their behavior in ROMP and especially for their use in the synthesis of poly(dicyclopentadiene) (pDCPD). Bearing either the common phosphine leaving ligand in the first and second Grubbs olefin metathesis catalysts, or the Ru-O bond cleavage for the next Hoveyda-type catalysts, this work is a step forward towards the control of polymer functionalization and living or switchable polymerizations. PMID- 26877820 TI - Genomic sequencing of a dyslexia susceptibility haplotype encompassing ROBO1. AB - BACKGROUND: The DYX5 locus for developmental dyslexia was mapped to chromosome 3 by linkage study of a large Finnish family, and later, roundabout guidance receptor 1 (ROBO1) was implicated as a candidate gene at DYX5 with suppressed expression from the segregating rare haplotype. A functional magnetoencephalographic study of several family members revealed abnormal auditory processing of interaural interaction, supporting a defect in midline crossing of auditory pathways. In the current study, we have characterized genetic variation in the broad ROBO1 gene region in the DYX5-linked family, aiming to identify variants that would increase our understanding of the altered expression of ROBO1. METHODS: We have used a whole genome sequencing strategy on a pooled sample of 19 individuals in combination with two individually sequenced genomes. The discovered genetic variants were annotated and filtered. Subsequently, the most interesting variants were functionally tested using relevant methods, including electrophoretic mobility shift assay (EMSA), luciferase assay, and gene knockdown by lentiviral small hairpin RNA (shRNA) in lymphoblasts. RESULTS: We found one novel intronic single nucleotide variant (SNV) and three novel intergenic SNVs in the broad region of ROBO1 that were specific to the dyslexia susceptibility haplotype. Functional testing by EMSA did not support the binding of transcription factors to three of the SNVs, but one of the SNVs was bound by the LIM homeobox 2 (LHX2) protein, with increased binding affinity for the non-reference allele. Knockdown of LHX2 in lymphoblast cell lines extracted from subjects from the DYX5-linked family showed decreasing expression of ROBO1, supporting the idea that LHX2 regulates ROBO1 also in human. CONCLUSIONS: The discovered variants may explain the segregation of dyslexia in this family, but the effect appears subtle in the experimental settings. Their impact on the developing human brain remains suggestive based on the association and subtle experimental support. PMID- 26877823 TI - TRANSPOSABLE REGULARIZED COVARIANCE MODELS WITH AN APPLICATION TO MISSING DATA IMPUTATION. AB - Missing data estimation is an important challenge with high-dimensional data arranged in the form of a matrix. Typically this data matrix is transposable, meaning that either the rows, columns or both can be treated as features. To model transposable data, we present a modification of the matrix-variate normal, the mean-restricted matrix-variate normal, in which the rows and columns each have a separate mean vector and covariance matrix. By placing additive penalties on the inverse covariance matrices of the rows and columns, these so called transposable regularized covariance models allow for maximum likelihood estimation of the mean and non-singular covariance matrices. Using these models, we formulate EM-type algorithms for missing data imputation in both the multivariate and transposable frameworks. We present theoretical results exploiting the structure of our transposable models that allow these models and imputation methods to be applied to high-dimensional data. Simulations and results on microarray data and the Netflix data show that these imputation techniques often outperform existing methods and offer a greater degree of flexibility. PMID- 26877821 TI - Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer. AB - BACKGROUND: While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. RESULTS: In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2 depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. CONCLUSIONS: Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC. PMID- 26877822 TI - Patterns of Alcohol Policy Enforcement Activities among Local Law Enforcement Agencies: A Latent Class Analysis. AB - AIMS: We assessed levels and patterns of alcohol policy enforcement activities among U.S. local law enforcement agencies. DESIGN/SETTING/PARTICIPANTS: We conducted a cross-sectional survey of a representative sample of 1,631 local law enforcement agencies across the 50 states. MEASURES/METHODS: We assessed 29 alcohol policy enforcement activities within each of five enforcement domains underage alcohol possession/consumption, underage alcohol provision, underage alcohol sales, impaired driving, and overservice of alcohol-and conducted a series of latent class analyses to identify unique classes or patterns of enforcement activity for each domain. FINDINGS: We identified three to four unique enforcement activity classes for each of the enforcement domains. In four of the domains, we identified a Uniformly Low class (i.e., little or no enforcement) and a Uniformly High enforcement activity class (i.e., relatively high levels of enforcement), with one or two middle classes where some but not all activities were conducted. The underage provision domain had a Uniformly Low class but not a Uniformly High class. The Uniformly Low class was the most prevalent class in three domains: underage provision (58%), underage sales (61%), and overservice (79%). In contrast, less than a quarter of agencies were in Uniformly High classes. CONCLUSIONS: We identified qualitatively distinct patterns of enforcement activity, with a large proportion of agencies in classes characterized by little or no enforcement and fewer agencies in high enforcement classes. An important next step is to determine if these patterns are associated with rates of alcohol use and alcohol-related injury and mortality. PMID- 26877824 TI - A MARKOV RANDOM FIELD-BASED APPROACH TO CHARACTERIZING HUMAN BRAIN DEVELOPMENT USING SPATIAL-TEMPORAL TRANSCRIPTOME DATA. AB - Human neurodevelopment is a highly regulated biological process. In this article, we study the dynamic changes of neurodevelopment through the analysis of human brain microarray data, sampled from 16 brain regions in 15 time periods of neurodevelopment. We develop a two-step inferential procedure to identify expressed and unexpressed genes and to detect differentially expressed genes between adjacent time periods. Markov Random Field (MRF) models are used to efficiently utilize the information embedded in brain region similarity and temporal dependency in our approach. We develop and implement a Monte Carlo expectation-maximization (MCEM) algorithm to estimate the model parameters. Simulation studies suggest that our approach achieves lower misclassification error and potential gain in power compared with models not incorporating spatial similarity and temporal dependency. PMID- 26877825 TI - Geometry of alpha-Cr2O3(0001) as a Function of H2O Partial Pressure. AB - Surface X-ray diffraction has been employed to elucidate the surface structure of alpha-Cr2O3(0001) as a function of water partial pressure at room temperature. In ultra high vacuum, following exposure to ~2000 Langmuir of H2O, the surface is found to be terminated by a partially occupied double layer of chromium atoms. No evidence of adsorbed OH/H2O is found, which is likely due to either adsorption at minority sites, or X-ray induced desorption. At a water partial pressure of ~30 mbar, a single OH/H2O species is found to be bound atop each surface Cr atom. This adsorption geometry does not agree with that predicted by ab initio calculations, which may be a result of some differences between the experimental conditions and those modeled. PMID- 26877826 TI - Chemical Interaction, Space-charge Layer and Molecule Charging Energy for a TiO2/TCNQ Interface. AB - Three driving forces control the energy level alignment between transition-metal oxides and organic materials: the chemical interaction between the two materials, the organic electronegativity and the possible space charge layer formed in the oxide. This is illustrated in this study by analyzing experimentally and theoretically a paradigmatic case, the TiO2(110) / TCNQ interface: due to the chemical interaction between the two materials, the organic electron affinity level is located below the Fermi energy of the n-doped TiO2. Then, one electron is transferred from the oxide to this level and a space charge layer is developed in the oxide inducing an important increase in the interface dipole and in the oxide work-function. PMID- 26877827 TI - Ambient Pressure XPS Study of Mixed Conducting Perovskite-Type SOFC Cathode and Anode Materials under Well-Defined Electrochemical Polarization. AB - The oxygen exchange activity of mixed conducting oxide surfaces has been widely investigated, but a detailed understanding of the corresponding reaction mechanisms and the rate-limiting steps is largely still missing. Combined in situ investigation of electrochemically polarized model electrode surfaces under realistic temperature and pressure conditions by near-ambient pressure (NAP) XPS and impedance spectroscopy enables very surface-sensitive chemical analysis and may detect species that are involved in the rate-limiting step. In the present study, acceptor-doped perovskite-type La0.6Sr0.4CoO3-delta (LSC), La0.6Sr0.4FeO3 delta (LSF), and SrTi0.7Fe0.3O3-delta (STF) thin film model electrodes were investigated under well-defined electrochemical polarization as cathodes in oxidizing (O2) and as anodes in reducing (H2/H2O) atmospheres. In oxidizing atmosphere all materials exhibit additional surface species of strontium and oxygen. The polaron-type electronic conduction mechanism of LSF and STF and the metal-like mechanism of LSC are reflected by distinct differences in the valence band spectra. Switching between oxidizing and reducing atmosphere as well as electrochemical polarization cause reversible shifts in the measured binding energy. This can be correlated to a Fermi level shift due to variations in the chemical potential of oxygen. Changes of oxidation states were detected on Fe, which appears as FeIII in oxidizing atmosphere and as mixed FeII/III in H2/H2O. Cathodic polarization in reducing atmosphere leads to the reversible formation of a catalytically active Fe0 phase. PMID- 26877828 TI - High-Temperature Carbon Deposition on Oxide Surfaces by CO Disproportionation. AB - Carbon deposition due to the inverse Boudouard reaction (2CO -> CO2 + C) has been studied on yttria-stabilized zirconia (YSZ), Y2O3, and ZrO2 in comparison to CH4 by a variety of different chemical, structural, and spectroscopic characterization techniques, including electrochemical impedance spectroscopy (EIS), Fourier-transform infrared (FT-IR) spectroscopy and imaging, Raman spectroscopy, and electron microscopy. Consentaneously, all experimental methods prove the formation of a more or less conducting carbon layer (depending on the used oxide) of disordered nanocrystalline graphite covering the individual grains of the respective pure oxides after treatment in flowing CO at temperatures above ~1023 K. All measurements show that during carbon deposition, a more or less substantial surface reduction of the oxides takes place. These results, therefore, reveal that the studied pure oxides can act as efficient nonmetallic substrates for CO-induced growth of highly distorted graphitic carbon with possible important technological implications especially with respect to treatment in pure CO or CO-rich syngas mixtures. Compared to CH4, more carbon is generally deposited in CO under otherwise similar experimental conditions. Although Raman and electron microscopy measurements do not show substantial differences in the structure of the deposited carbon layers, in particular, electrochemical impedance measurements reveal major differences in the dynamic growth process of the carbon layer, eventually leading to less percolated islands and suppressed metallic conductivity in comparison to CH4-induced graphite. PMID- 26877829 TI - Enthalpy Effect of Adding Cobalt to Liquid Sn-3.8Ag-0.7Cu Lead-Free Solder Alloy: Difference between Bulk and Nanosized Cobalt. AB - Heat effects for the addition of Co in bulk and nanosized forms into the liquid Sn-3.8Ag-0.7Cu alloy were studied using drop calorimetry at four temperatures between 673 and 1173 K. Significant differences in the heat effects between nano and bulk Co additions were observed. The considerably more exothermic values of the measured enthalpy for nano Co additions are connected with the loss of the surface enthalpy of the nanoparticles due to the elimination of the surface of the nanoparticles upon their dissolution in the liquid alloy. This effect is shown to be independent of the calorimeter temperature (it depends only on the dropping temperature through the temperature dependence of the surface energy of the nanoparticles). Integral and partial enthalpies of mixing for Co in the liquid SAC-alloy were evaluated from the experimental data. PMID- 26877830 TI - Phosphodiesterase 6beta Expression In Developing Mouse Retina. AB - The rd1 mouse is a well-studied model of retinitis pigmentosa (RP), an inherited retinal degenerative disease affecting approximately 1 in 4000 people. It is characterized by a mutation in the Pde6b gene that codes for Phosphodiesterase 6beta (PDE6beta), a downstream effector of phototransduction. Pde6b gene expression occurs embryonically in mouse retina, whereas other proteins involved in phototransduction are expressed around postnatal day 5 (P5). The primary aim of this study is to investigate the temporal and spatial expression pattern of PDE6beta protein during photoreceptor development. Using Western blots with wild type and rd1 mouse retinas from P2 - P21 we demonstrated that PDE6beta protein is expressed in wild type retinas by P2 and is not detected in rd1 retinas. The earliest detection of PDE6beta in wild type retinas by immunohistochemistry was at P6, where it was confined to the apical region of the photoreceptor layer. The expression of PDE6beta protein prior to differentiation of photoreceptor cells and prior to expression of other phototransduction proteins is consistent with the hypothesis that PDE6beta may play a role during photoreceptor development distinct from its role in phototransduction. Our lab previously showed that Prenylated Rab Acceptor 1 (PRA1), a vesicular trafficking protein, is downregulated in the developing rd1 retina, although its function in the retina is unknown. The second aim of this study was to explore the relationship between PRA1 and PDE6beta. We used immunohistochemistry to determine whether the two proteins are co-localized during the postnatal differentiation period. However, no co-localization between PDE6beta and PRA1 was detected. The function of PRA1 in developing retina remains to be elucidated. PMID- 26877832 TI - Transforming the Medical Subject Headings into Linked Data: Creating the Authorized Version of MeSH in RDF. AB - In February 2014 the National Library of Medicine formed the Linked Data Infrastructure Working Group to investigate the potential for publishing linked data, determine best practices for publishing linked data, and prioritize linked data projects, beginning with transforming the Medical Subject Headings as a linked data pilot. This article will review the pilot project to convert the Medical Subject Headings from XML to RDF. It will discuss the collaborative process, the technical and organizational issues tackled, and the future of linked data at the library. PMID- 26877831 TI - Depression and HIV Risk Taking among Men Who Have Sex with Other Men (MSM) and Who Use the Internet to Find Partners for Unprotected Sex. AB - PURPOSE: This study examines the prevalence of depression in a sample of MSM who are at high risk for HIV. It examines the relationship between depressive symptomatology and involvement in HIV risk behaviors, and the factors associated with greater depressive symptomatology. METHODS: The data come from a national random sample of 332 MSM who used any of 16 websites to identify men with whom they could engage in unprotected sex. Data were collected via telephone interviews. RESULTS: Depression was more prevalent in this population (26.7%) than among men in the general population. Depression was not related directly to any of the HIV risk behaviors examined, but it was related to men's attitudes toward condom use, which was the strongest predictor of their involvement in risky behaviors. Five factors were identified as being associated with greater depression: lower educational attainment, greater discrimination based on sexual orientation, greater eroticizing of ejaculatory fluids, experiencing more substance abuse problems, and greater childhood maltreatment. CONCLUSIONS: Depression is a consequential problem in this population. Although depression does not appear to be related directly to HIV risk practices in this population, its influence cannot be discounted because of its effects on other key predictors of risk involvement. PMID- 26877833 TI - LANDMARK MATCHING ON THE SPHERE USING DISTANCE FUNCTIONS. AB - Nonlinear registration of 3D surfaces is important in many medical imaging applications, including the mapping of longitudinal changes in anatomy, or of multi-subject functional MRI data to a canonical surface for comparison and integration. To register 3D surfaces, such as the cortical surface of the brain, one approach is to transform them first to planar or spherical objects. Internal landmarks can then be matched on these simpler parameter domains. Here we study the diffeomorphic matching of landmarks on the sphere. Our method builds on the level set technique of Leow et al. [1] for the plane. Both forward and backward matching terms are included, thus ensuring the invertibility of the representation. We demonstrate our technique on a pair of lines on the sphere. The overall approach improves on earlier work in cortical matching by allowing the matching energy to be relaxed along sulcal landmarks, minimizing distortion, and also enables point and curve landmarks to be aligned in the same general framework as densely-defined scalar fields, such as curvature or cortical thickness maps. PMID- 26877835 TI - Treatment of BG-1 Ovarian Cancer Cells Expressing Estrogen Receptors with Lambda cyhalothrin and Cypermethrin Caused a Partial Estrogenicity Via an Estrogen Receptor-dependent Pathway. AB - Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC (10(-6) M) and CP (10(-5) M) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 (10(-8) M), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, ERalpha expression was not significantly changed by LC and CP, while downregulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model. PMID- 26877834 TI - Mitochondria in Cancer Energy Metabolism: Culprits or Bystanders? AB - Cancer is a disease characterized by uncontrolled growth. Metabolic demands to sustain rapid proliferation must be compelling since aerobic glycolysis is the first as well as the most commonly shared characteristic of cancer. During the last decade, the significance of metabolic reprogramming of cancer has been at the center of attention. Nonetheless, despite all the knowledge gained on cancer biology, the field is not able to reach agreement on the issue of mitochondria: Are damaged mitochondria the cause for aerobic glycolysis in cancer? Warburg proposed the damaged mitochondria theory over 80 years ago; the field has been testing the theory equally long. In this review, we will discuss alterations in metabolic fluxes of cancer cells, and provide an opinion on the damaged mitochondria theory. PMID- 26877837 TI - Effect of Hfe Deficiency on Memory Capacity and Motor Coordination after Manganese Exposure by Drinking Water in Mice. AB - Excess manganese (Mn) is neurotoxic. Increased manganese stores in the brain are associated with a number of behavioral problems, including motor dysfunction, memory loss and psychiatric disorders. We previously showed that the transport and neurotoxicity of manganese after intranasal instillation of the metal are altered in Hfe-deficient mice, a mouse model of the iron overload disorder hereditary hemochromatosis (HH). However, it is not fully understood whether loss of Hfe function modifies Mn neurotoxicity after ingestion. To investigate the role of Hfe in oral Mn toxicity, we exposed Hfe-knockout (Hfe (-/-)) and their control wild-type (Hfe (+/+)) mice to MnCl2 in drinking water (5 mg/mL) for 5 weeks. Motor coordination and spatial memory capacity were determined by the rotarod test and the Barnes maze test, respectively. Brain and liver metal levels were analyzed by inductively coupled plasma mass spectrometry. Compared with the water-drinking group, mice drinking Mn significantly increased Mn concentrations in the liver and brain of both genotypes. Mn exposure decreased iron levels in the liver, but not in the brain. Neither Mn nor Hfe deficiency altered tissue concentrations of copper or zinc. The rotarod test showed that Mn exposure decreased motor skills in Hfe (+/+) mice, but not in Hfe (-/-) mice (p = 0.023). In the Barns maze test, latency to find the target hole was not altered in Mn exposed Hfe (+/+) compared with water-drinking Hfe (+/+) mice. However, Mn exposed Hfe (-/-) mice spent more time to find the target hole than Mn-drinking Hfe (+/+) mice (p = 0.028). These data indicate that loss of Hfe function impairs spatial memory upon Mn exposure in drinking water. Our results suggest that individuals with hemochromatosis could be more vulnerable to memory deficits induced by Mn ingestion from our environment. The pathophysiological role of HFE in manganese neurotoxicity should be carefully examined in patients with HFE associated hemochromatosis and other iron overload disorders. PMID- 26877836 TI - Endosulfan Induces CYP1A1 Expression Mediated through Aryl Hydrocarbon Receptor Signal Transduction by Protein Kinase C. AB - CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways. PMID- 26877838 TI - Effects of Styrene-metabolizing Enzyme Polymorphisms and Lifestyle Behaviors on Blood Styrene and Urinary Metabolite Levels in Workers Chronically Exposed to Styrene. AB - The aim of this study was to investigate whether genetic polymorphisms of CYP2E1, GSTM1, and GSTT1 and lifestyle habits (smoking, drinking, and exercise) modulate the levels of urinary styrene metabolites such as mandelic acid (MA) and phenylglyoxylic acid (PGA) after occupational exposure to styrene. We recruited 79 male workers who had received chronic exposure in styrene fiberglass reinforced plastic manufacturing factories. We found that serum albumin was significantly correlated with blood styrene/ambient styrene (BS/AS), urinary styrene (US)/AS, and US/BS ratios as well as urinary metabolites, that total protein correlated with US/MA and US/PGA ratios, and that low density lipoprotein (LDL)-cholesterol significantly correlated with US/BS, US/MA, and US/PGA ratios. Multiple logistic regression analyses using styrene-metabolizing enzyme genotypes and lifestyle habits as dependent variables and blood and urine styrene concentrations and urine styrene metabolite levels as independent variables revealed that CYP2E1*5 was associated with the MA/US ratio and GSTM1 with US/BS, that a smoking habit was associated with US/AS and MA/US ratios and MA and PGA levels, and that regular exercise was correlated with PGA/US. In conclusion, the results suggested that genetic polymorphisms of styrene-metabolizing enzymes, lifestyle behaviors, and albumin and LDL-cholesterol serving as homeostasis factors together are involved in styrene metabolism. PMID- 26877840 TI - Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats. AB - TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 MUg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 MUg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 MUg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 MUg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 MUg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats. PMID- 26877839 TI - Antioxidant Activity and Anti-wrinkle Effects of Aceriphyllum rossii Leaf Ethanol Extract. AB - We evaluated the antioxidant activity and anti-wrinkle effects of Aceriphyllum rossii leaf ethanol extract (ARLEE) in vitro using human dermal fibroblasts. The total polyphenol and flavonoid contents of ARLEE were 578.6 and 206.3 mg/g, respectively. At a concentration of 250 MUg/mL, the electron-donating ability of ARLEE was 87.1%. In comparison with the vehicle, ARLEE treatment at 100 MUg/mL significantly increased type I procollagen synthesis (p < 0.01) by 50.7%. In vitro ARLEE treatment (10 mg/mL) inhibited collagenase and elastase activity by 97.1% and 99.2%, respectively. Compared with the control, ascorbic acid treatment at 100 MUg/mL significantly decreased matrix metalloproteinase (MMP)-1 protein expression (p < 0.01) by 37.0%. ARLEE treatment at 50 MUg/mL significantly decreased MMP-1 protein expression (p < 0.01) by 46.1%. Ascorbic acid and ARLEE treatments at 100 MUg/mL significantly decreased MMP-1 mRNA expression (p < 0.01) by 26.1% and 36.1%, respectively. From these results, we conclude that ARLEE has excellent antioxidant activity and even better anti-wrinkle effects than ascorbic acid in human dermal fibroblasts. These results suggest that ARLEE could be used in functional cosmetics for the prevention or alleviation of skin wrinkles induced by ultraviolet rays. PMID- 26877841 TI - A Study on Subchronic Inhalation Toxicity of 1-Chloropropane. AB - This study was conducted to measure toxicity of 1-chloropropane (CAS No. : 540-54 5). According to the OECD Test Guideline 413 (Subchronic inhalation toxicity: 90 day study), SD rats were exposed to 0, 310, 1,250, and 5,000 ppm of 1 chloropropane for 6 h/day, 5 day/week for 13 weeks via whole-body inhalation. Mortality, clinical signs, body weights, food consumption, motor activity, ophthalmoscopy, hematology, serum chemistry, urinalysis, organ weights, gross and histopathological findings were compared between control and all tested groups. No mortality or remarkable clinical signs were examined during the study. No gross lesions or adverse effects on body weight, food consumption, motor activity, ophthalmoscopy, urinalysis, hematology, organ weights were observed in any of male or female rats in all tested groups. In serum biochemistry, glucose was significantly decreased in males of 1,250 and 5,000 ppm groups compared to control group in dose-dependent relationship. In histopathological examination, vacuolation of acinar cells was observed in pancreas of all male and female groups exposed to 1-chloropropane. In conclusion, no observable adverse effect level (NOAEL) was considered to be below 310 ppm/6 h/day, 5 day/week for rats. PMID- 26877842 TI - Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats. AB - Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID- 26877843 TI - Job Stress and Neuropeptide Response Contributing to Food Intake Regulation. AB - The purpose of the present study is to investigate the correlations between food intake behavior and job stress level and neuropeptide hormone concentrations. Job strain and food intake behavior were first identified using a self-reported questionnaire, concentrations of neuropeptide hormones (adiponectin, brain derived neurotrophic factor [BDNF], leptin, and ghrelin) were determined, and the correlations were analyzed. In the results, job strain showed significant correlations with adiponectin (odds ratio [OR], 1.220; 95% confidence interval [CI], 1.001~1.498; p < 0.05) and BDNF (OR, 0.793; 95% CI, 0.646~0.974; p < 0.05), and ghrelin exhibited a significant correlation with food intake score (OR, 0.911; 95% CI, 0.842~0.985, p < 0.05). These results suggest that job stress affects food intake regulation by altering the physiological concentrations of neuropeptide hormones as well as emotional status. PMID- 26877845 TI - In vitro and in vivo evaluation of a novel testosterone transdermal delivery system (TTDS) using palm oil base. AB - OBJECTIVE S: Transdermal preparations for testosterone are becoming popular because of their unique advantages such as avoidance of first-pass effect, convenience, improved bioavailability, and reduction of systemic side effects. A novel testosterone transdermal delivery system (TDDS) was developed using a palm oil base called HAMINTM (a commercial product) and tested using in vitro and in vivo skin permeability test methods. MATERIALS AND METHODS: The physical characteristics of the formulation such as particle size and viscosity were determined by using Franz diffusion cell and Brookfield viscometer, respectively. In vivo skin permeability test was performed on healthy rabbits through the skin. Testosterone in serum was analyzed using the validated Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) technique. RESULTS: In vitro study showed that the cumulative amount of testosterone diffused was between 40 to 1400 ngcm( )2 over a period of five hr after application of TDDS through the artificial Strat-MTM membrane. In the in vivo rabbit skin permeability test, the results indicated that testosterone was well absorbed with a mean Cmax and Tmax of 60.94 ngml(-1) and 2.29 hr after application of TDDS while no increase was observed in placebo treatment. Particle size analysis ranged from 79.4 nm to 630.0 nm for placebo and 97 to 774.0 nm for TDDS. CONCLUSION: The formulation was successfully prepared using HAMINTM, which has demonstrated great potential for topical delivery of testosterone. PMID- 26877844 TI - Razi's Al-Hawi and saffron (Crocus sativus): a review. AB - Traditional knowledge can be used as a source for development of new medicines. In the present study, we compare the data on saffron in Razi's Al-Hawi book with modern scientific studies. A computerized search of published articles was performed using MEDLINE, Scopus as well as native references. The search terms used were saffron, Crocus sativus, crocetin, crocin, safranal, Razi, and Al-Hawi. A variety of properties of saffron including diuretic, analgesic, anti inflammatory, hepatoprotective, appetite suppressant, hypnotic, antidepressant, and bronchodilator effects were mentioned in Al-Hawi. Modern studies also confirmed most of these characteristics. This review indicates that the pharmacological data on saffron and its constituents are similar to those found in Razi's Al-Hawi monograph and it can be concluded that ethnobotanical information and ancient sources have precious data about medicinal plants that lead to finding new compounds for treatment of several diseases. PMID- 26877846 TI - The effects of long-term leptin administration on morphometrical changes of mice testicular tissue. AB - OBJECTIVES: Leptin is a novel and interesting hormone for anyone trying to lose weight, but its effects on male gonad structure in longitudinal study is unknown. The present study was designed to explore morphometrical changes of mouse testicular tissue after long-term administration of leptin. MATERIALS AND METHODS: Thirty healthy mature male mice were randomly assigned to either control (n=15) or treatment (n=15) groups. Leptin was intraperitoneally injected to the treatment group (0.1 ug/100 ul of physiological saline) once a day for 30 consecutive days, and control animals received normal saline with the same volume and route. Five mice from each experimental group were sacrificed at 15, 30 and 60 days after the beginning of treatments. Left testes were removed, weighted and then fixed in 10% buffered formalin, and stained with hematoxylin and eosine for morphometrical assays. RESULTS: Except for sertoli cell nucleus diameter, which was affected from 30(th) day, evaluation of other morphometrical parameters such as Johnsen's score, meiotic index, spermatogenesis, epithelial height, seminiferous tubules diameter and spermatogonial nucleus diameter revealed significant decrease from 15(th) day after leptin administration compare to those of the control group (P<0.05). Thus, meiotic index and spermatogonial cell nucleus diameter were two parameters that were further disturbed on 30(th) day compare to the day 15 (3.09+/-0.03 vs. 3.23+/-0.03, P=0.006 and 5.50+/-0.09 vs. 6.08+/-0.14, P=0.007, respectively). CONCLUSION: Our results showed that long term administration of leptin could disturb testicular tissue structure and delay spermatogenesis process. PMID- 26877847 TI - Repeated injections of orexin-A developed behavioral tolerance to its analgesic effects in rats. AB - OBJECTIVES: Reduction of pharmacological effectiveness or tolerance appears following repeated administration of many analgesic drugs. We investigated tolerance to anti-nociceptive effects of orexin-A, an endogenous potent analgesic peptide using the hot-plate test. MATERIALS AND METHODS: Orexin-A was microinjected ICV (intracerebroventricular) with an interval of 12 hr for 7 continuous days and its anti-nociceptive responses were measured on days 1, 4 and 7 using the hot-plate test following the first day of administration. Orexin-A was used at a dose of 100 pmol to induce analgesic effects. RESULTS: ICV administration of orexin-A produced an effective anti-nociception on the first day of experiment as measured by hot-plate 5, 15, and 30 min after the injection, in comparison with both baselines (hot-plate test one day before the beginning of orexin-A administration and control, saline-administrated group). However, repeated administration of orexin-A on the following days revealed a significant reduction in this analgesic effect during day 4 to day 7. However, to rule out any associative tolerance resulting from learning related to experimental procedures and/or environmental cues, a single injection of orexin-A was administrated to animals of control group (which were receiving saline during 7 days of experiments) and the analgesic effect was observed. CONCLUSION: These results, for the first time, indicated the appearance of tolerance to anti nociceptive effects of orexin-A, following repeated administrations of this agent. PMID- 26877848 TI - Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms. AB - OBJECTIVES: IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. MATERIALS AND METHODS: Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP. RESULTS: The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL 33/IL-12 ratio were significantly higher in patients than the control group (P<0.001). The IL-33 levels and IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and rs1929992 between patients and the control group. No significant differences were observed between subjects with various genotypes at rs3212227 and rs1929992 with respect to related cytokine levels. CONCLUSION: These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy. PMID- 26877849 TI - Fluorescence spectra of cardiac myosin and in vivo experiment: studies on daunorubicin-induced cardiotoxicity. AB - OBJECTIVES: The objective of this study was to investigate the interaction of daunorubicin (DNR) and cardiac myosin (CM) and the changes in mice hearts to exhibit DNR-induced cardiotoxicity. MATERIALS AND METHODS: The interaction between DNR and CM was expressed using fluorescence quenching at pH 4.0-9.0 and 15-37 degrees C. DNR-induced cardiotoxicity was studied using in vivo experiment. Forty groups mice were used control group in which mice were treated with DNR orally, and three DNR-treated groups in which mice were injected intraperitoneally with DNR at seven bolus doses of 2.0, 4.0, and 6.0 mg/kg body weight, respectively. Heart indices and myocardial enzyme levels were obtained by histopathological and biochemical analysis. RESULTS: The fluorescence quenching mechanism of DNR-CM complex was observed to be a static procedure at 20 degrees C (pH 7.4), and weakly acidic environment (pH 4.0-6.0) or higher temperature (30 37 degrees C) promoted the interaction between DNR and CM, causing variations in conformation and normal physiological functions of CM. Thermodynamic studies demonstrated that the binding of DNR to CM was a spontaneous process driven by entropy. It also indicated that hydrophobic interaction and hydrogen bonds may play essential roles in the combination of DNR with CM. In addition, 4.0-6.0 mg/kg DNR-treated mice exhibited obvious histopathological lesion, increase in myocardial enzyme level, and reductions in blood cell count. CONCLUSION: Our results are valuable for better understanding the particular mode of DNR-CM interaction, and are important to have a deeper insight into the DNR-induced cardiotoxicity. PMID- 26877850 TI - Deregulation of miR-21 and miR-155 and their putative targets after silibinin treatment in T47D breast cancer cells. AB - OBJECTIVES: MicroRNAs (miRNAs) are a class of short RNAs that control the biological processes including cell proliferation, apoptosis and development. Aberrant expression of miRNAs was determined in the different stages of tumor development and metastasis. To study the effect of silibinin on miRNAs expression, we evaluated quantitative expression of miR-21 and miR-155 as two oncomiRs and several potential targets in silibinin-treated T47D cells. MATERIALS AND METHODS: The rate of proliferation and apoptosis was measured in silibinin treated and untreated cells. The expression levels of miR-21 and miR-155 were evaluated in T47D cells treated with silibinin (100 ug/ml). Also, their putative targets were predicted in apoptotic pathways using multiple algorithms; as a confirmation, the transcription level of APAF-1, CASP-9 and BID was evaluated. RESULTS: In silibinin-treated cells, death was occurred in a dose and time dependent manner. miR-21 and miR-155 was downregulated in cells treated with silibinin (100 ug/ml). It is noticeable that the expression of their potential targets including CASP-9 and APAF-1 was increased in silibinin-treated cells after 48 hr. CONCLUSION: Our findings showed a correlation between the expression of miR-21 and miR-155 and apoptosis in silibinin treated T47D cells. It seems that miRNAs such as miR-21 and miR-155 were regulated by silibinin. Also, increase in the transcript level of APAF-1 and CASP-9 after downregulation of miR 21 and miR-155 might indicate that these genes were targeted by aforementioned miRNAs in T47D cells. PMID- 26877851 TI - SCN1A and SCN1B gene polymorphisms and their association with plasma concentrations of carbamazepine and carbamazepine 10, 11 epoxide in Iranian epileptic patients. AB - OBJECTIVE S: From a genetic point of view, epilepsy is a polygenic multifactorial syndrome. The SCN1A and B genes belong to a family of genes that provide instructions for making sodium channels. Understanding the relevance of SCN1A and SCN1B gene polymorphisms to plasma concentration of carbamazepine (CBZ) and 'its active metabolite carbamazepine 10, 11 epoxide (CBZE), may shed more light on inter-individual variations in response to CBZ. MATERIALS AND METHODS: In this cross-sectional study, genotype distribution and allele frequency of six non synonymous exonic single nucleotide polymorphisms (SNPs) of the SCN1A and B genes were selected and determined using PCR-RFLP in 70 epileptic patients treated with CBZ for at least 6 months. The patients had no hepatic or renal diseases and received no medications known to have a major interaction with CBZ. Serum concentrations of CBZ and CBZE were measured using High-Performance Liquid Chromatography (HPLC). RESULTS: The AA, AG and GG alleles of SCN1A were found in 23, 37 and 10 patients, respectively. There were no statistically significant differences in the mean (+/- standard deviation) of plasma concentrations of CBZ (P=0.8) and CBZE (P=0.1) among these 3 groups. Likewise, there was no statistically significant relationship between SCN1A polymorphisms and CBZ concentration/dose ratio (P=0.7). A significant association was found between CBZ plasma level and CBZ concentration/dose with CBZ daily dose. All patients had the same genotype of SCN1B gene(CC). and no statistical analysis was performed. CONCLUSION: No significant association between SCN1A gene polymorphisms and plasma levels of CBZ and CBZE were found[u1]. PMID- 26877852 TI - Mesenchymal stem cells can survive on the extracellular matrix-derived decellularized bovine articular cartilage scaffold. AB - OBJECTIVE S: The scarcity of articular cartilage defect to repair due to absence of blood vessels and tissue engineering is one of the promising approaches for cartilage regeneration. The objective of this study was to prepare an extracellular matrix derived decellularized bovine articular cartilage scaffold and investigate its interactions with seeded rat bone marrow mesenchymal stem cells (BM-MSCs). MATERIALS AND METHODS: Bovine articular cartilage that was cut into pieces with 2 mm thickness, were decellularized by combination of physical and chemical methods including snap freeze-thaw and treatment with sodium dodecyl sulfate (SDS). The scaffolds were then seeded with 1, 1'-dioctadecyl-3, 3, 3', 3' tetramethylindocarbocyanine perchlorate (DiI) labeled BM-MSCs and cultured for up to two weeks. RESULTS: Histological studies of decellularized bovine articular cartilage showed that using 5 cycles of snap freeze-thaw in liquid nitrogen and treatment with 2.5% SDS for 4 hr led to the best decellularization, while preserving the articular cartilage structure. Adherence and penetration of seeded BM-MSCs on to the scaffold were displayed by histological and florescence examinations and also confirmed by electron microscopy. CONCLUSION: ECM-derived decellularized articular cartilage scaffold provides a suitable environment to support adhesion and maintenance of cultured BM-MSCs and could be applied to investigate cellular behaviors in this system and may also be useful for studies of cartilage tissue engineering. PMID- 26877853 TI - Case-control study on peroxisome proliferator-activated receptor gamma polymorphism and interaction with HDL on essential hypertension in Chinese Han. AB - OBJECTIVES: To investigate the association of single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors gamma (PPARG) with essential hypertension (EH) and additional role of gene- high-density lipoprotein cholesterol (HDL) interaction. MATERIALS AND METHODS: A total of 1640 patients with EH (806 males, 834 females), with a mean age of 52.5+/-12.6 years, were selected, including 816 EH patients and 824 controls, who were enrolled from the community. Three SNPs were selected for genotyping in the case-control study: rs10865710, rs709158, rs1805192. Logistic regression model was used to examine the interaction between SNP and HDL on EH, odds ratio (OR) and 95% confidence interval (95% CI) were also calculated. RESULTS: All genotypes were distributed according to Hardy-Weinberg equilibrium in controls. Logistic regression analysis showed an association between genotypes of variants in rs1805192 and decreased EH risk, EH risk was significantly lower in carriers of Ala allele of the rs1805192 polymorphism than those with Pro/Pro (Pro/Ala+ Ala/Ala versus Pro/Pro, adjusted OR (95% CI) =0.65 (0.53-0.83), after covariate adjustment. In addition, the Ala allele of the rs1805192 polymorphism was also associated with diastolic blood pressure (DBP), but not systolic blood pressure (SBP), we also found, by interaction analysis, combined effect of rs1805192 and HDL on EH risk after covariate adjustment. CONCLUSION: Our results support an important association between rs1805192 minor allele (Ala allele) of PPARG and lower EH risk, the interaction analysis showed a combined effect of Ala- HDL on lower EH risk. PMID- 26877854 TI - Effects of cardiopulmonary bypass on lung nuclear factor-kappa B activity, cytokine release, and pulmonary function in dogs. AB - OBJECTIVES: To study the effect of cardiopulmonary bypass (CPB) on nuclear factor kappa B (NF-kappaB) and cytokine expression and pulmonary function in dogs. MATERIALS AND METHODS: Twelve male mongrel dogs were divided into a methylprednisolone group (group M) and a control group (group C). All animals underwent aortic and right atrial catheterization under general anesthesia. Changes in pulmonary function and hemodynamics were monitored and the injured site was histologically evaluated. RESULTS: The activity of NF-kappaB and myeloperoxidase (MPO), levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8, and the wet/dry (W/D) weight ratio were significantly higher after CPB than before CPB in both groups (P<0.01), with the lower values in group M than in group C, at different time points (P<0.01). Histological evaluation revealed neutrophilic infiltration and thickening of the alveolar interstitium in both groups; however, the degree of pathological changes was significantly lower in group M than in group C. The alveolar-arterial O2 tension difference (PA-aDO2) was significantly higher after CPB than before CBP (P<0.01), and lower in group M than in group C (P<0.01). The pulmonary compliance after removal of the aortic clamp obviously decreased in group C (P<0.05), with no significant change in group M. CONCLUSION: CPB can significantly enhance the activation of NF-kappaB in lung tissues and increase the expression of inflammatory cytokines, thus inducing lung injury. Methylprednisolone can inhibit the NF-kappaB activation, thus inhibiting the release of cytokines and protecting the lung function. PMID- 26877855 TI - Screening and identification of SUMP-proteins in sub-acute treatment with diazinon. AB - OBJECTIVES: Small ubiquitin-like modifiers (SUMOs) are a family of ubiquitin related, proteins that are involved in a wide variety of signaling pathways. SUMOylation, as a vital post translational modification, regulate protein function in manycellular processes. Diazinon (DZN), an organophosphate insecticide, causses oxidative stress and subsequently programmed cell death in different tissues. The aim of this study was to evaluate the role and pattern of SUMO modificationas a defense mechanism against stress oxidative, in the heart tissuesof the DZN treated rats. MATERIALS AND METHODS: Diazinon (15 mg/kg/day), corn oil (control) were administered via gavageto male Wistar rats for four weeks. SUMO1 antibody was covalently crosslinked to protein A/G agarose. heart tissue lysate were added to agarosebeads, After isolation of target proteins(SUMO1- protein)SDS-PAGE gel electrophoresis was performed. Protein bands were identified using MALDI-TOF/TOF and MASCOT). Fold change of (DZN/Ctrl) separated proteins was evaluated using UVband software (UVITEC, UK). RESULTS: Our result showed that subacute exposure to DZN increased SUMOylationoffour key proteins involved in the metabolic process including; Acyl-CoA dehydrogenase, creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and ATP synthase, in the heart tissue of animals. A probability value of less than 0.05 was considered significant (P<0.05). CONCLUSION: It seems that protein SUMOylation provides a safeguard mechanism against DZN Toxicity. PMID- 26877856 TI - Improvement effect of Lycium barbarum polysaccharide on sub-health mice. AB - OBJECTIVES: Sub-health has been described as a chronic condition of unexplained deteriorated physiological function, which falls between health and illness. In the present study, we evaluated the effects of Lycium barbarum polysaccharide (LBP), a polysaccharide fraction purified from Lycium barbarum (L. barbarum) on the sub-health mice. MATERIALS AND METHODS: The sub-health model mice were built through compound factors. The mice were given intragastric administration of LBP at low dose (50 mg*kg-1) and high dose (100 mg*kg-1), respectively. After LBP treatment for 4 weeks, the antioxidant ability, enhancing immune function and anti-fatigue activity were detected. RESULTS: The results showed that LBP could enhance antioxidant ability in sub-health mice. LBP could effectively improve immunity of sub-health mice and protect the immune organs, such as thymus. In addition, LBP showed anti-fatigue ability in sub-health mice. CONCLUSION: LBP could improve sub-health state caused from composite factor through three aspects, such as increasing antioxidant ability, promoting T lymphocyte proliferation, inhibiting thymus lymphocyte apoptosis, and alleviating fatigue. PMID- 26877857 TI - Cholesterol suppresses antimicrobial effect of statins. AB - OBJECTIVES: Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. MATERIALS AND METHODS: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria using gel diffusion assay. RESULTS: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. CONCLUSION: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol. PMID- 26877858 TI - Effects of gamma oryzanol on factors of oxidative stress and sepsis-induced lung injury in experimental animal model. AB - OBJECTIVE S: There is corroborating evidence to substantiate redox imbalance and oxidative stress in sepsis that finally leads to organ damage or even death. Gamma oryzanol (GO) is one of the major bioactive components in rice bran has been considered to function as an antioxidant. The present study was carried out to evaluate the antioxidant activity of gamma oryzanol in vitro and its efficacy in sepsis. MATERIALS AND METHODS: To induce sepsis, cecal ligation and puncture (CLP) method was performed on the rats. A study group of forty male Wistar rats were divided into the following groups: sham group; CLP group; 50 mg/kg GO- treated CLP group and 100 mg/kg GO- treated CLP group. GO was administered with an oral gavage 2 hr prior to inducing sepsis. Tissue and blood samples were collected 12 hr after CLP to prepare tissue sections for histopathological study and assay the oxidative stress biomarkers including: SOD (Superoxide Dismutase), TAC (total antioxidant capacity), MDA (Malondialdehyde), MPO (Myeloperoxidase) and PAI-1 (Plasminogen Activator Inhibitor-1). Data are given as mean +/- SD. The ANOVA with Tukey post hoc test was used to determine the differences between groups and P <0.05 was considered as statistical significance. RESULTS: TAC level increased in GO- treated CLP groups (P<0.05). Inflammation score of lung tissue and MPO activity were significantly lower in GO treated CLP group (P<0.05). CONCLUSION: It seems that GO has a protective effect on lung inflammation and improves the body redox capacity during sepsis. PMID- 26877859 TI - Bias in Methicillin Resistance of Staphylococcus aureus. PMID- 26877860 TI - Corrigendum to: Comparison of Serum Hepatitis B Virus DNA and HBsAg Levels Between HBeAg-Negative and HBeAg-Positive Chronic Hepatitis B Patients [Published in Jundishapur Journal of Microbiology. 2015 March; 8(3): e21444]. PMID- 26877863 TI - Structure Elucidation of Nigricanoside A Through Enantioselective Total Synthesis. AB - Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID- 26877862 TI - Potentiation of Francisella Resistance to Conventional Antibiotics through Small Molecule Adjuvants. AB - A screen of 20 compounds identified small molecule adjuvants capable of potentiating anitbiotic activty against Francisella philomiragia. Analogue synthesis of an initial hit compound led to the discovery of a potentially new class of small molecule adjuvants containg an indole core. The lead compound was able to lower the MIC of colistin by 32-fold against intrinsically resistant F. philomiragia. PMID- 26877864 TI - First pi-linker featuring mercapto and isocyano anchoring groups within the same molecule: Synthesis, heterobimetallic complexation and self-assembly on Au(111). AB - Mercapto (-SH) and isocyano (-N=C) terminated conducting pi-linkers are often employed in the ever-growing quest for organoelectronic materials. While such systems typically involve symmetric dimercapto or diisocyano anchoring of the organic bridge, this article introduces the chemistry of a linear azulenic pi linker equipped with one mercapto and one isocyano terminus. The 2-isocyano-6 mercaptoazulene platform was efficiently accessed from 2-amino-6-bromo-1,3 diethoxycarbonylazulene in four steps. The 2-N=C end of this 2,6-azulenic motif was anchrored to the [Cr(CO)5] fragment prior to formation of its 6-SH terminus. Metalation of the 6-SH end of [(OC)5Cr(eta1-2-isocyano-1,3-diethoxycarbonyl-6 mercaptoazulene)] (7) with Ph3PAuCl, under basic conditions, afforded X-ray structurally characterized heterobimetallic Cr0/AuI ensemble [(OC)5Cr(MU eta1:eta1-2-isocyano-1,3-diethoxycarbonyl-6-azulenylthiolate)AuPPh3] (8). Analysis of the 13C NMR chemical shifts for the [(NC)Cr(CO)5] core in a series of the related complexes [(OC)5Cr(2-isocyano-6-X-1,3-diethoxy-carbonylazulene)] (X = -N=C, Br,H, SH, SCH2CH2CO2CH2CH3, SAuPPh3) unveiled remarkably consistent inverse linear correlations delta( 13COtrans) vs. delta( 13CN) and delta( 13COcis) vs. delta( 13CN) that appear to hold well beyond the above 2-isocyanoazulenic series to include complexes [(OC)5Cr(CNR)] containing strongly electron-withdrawing substituents R, such as CF3, CFClCF2Cl, C2F3, and C6F5. In addition to functioning as asensitive 13C NMR handle, the essentially C4v-symmetric [( NC)Cr(CO)5] moiety proved to be an informative, remote, nuN=C/nuC=O infrared reporter in probing chemisorption of 7 on the Au(111) surface. PMID- 26877865 TI - MiR-690, a Runx2-targeted miRNA, regulates osteogenic differentiation of C2C12 myogenic progenitor cells by targeting NF-kappaB p65. AB - BACKGROUND: The runt-related transcription factor 2 (Runx2) is a cell-fate determining factor that controls osteoblast differentiation and bone formation. It has been previously demonstrated that microRNAs (miRNAs) play important roles in osteogenesis. However, the Runx2-regulated miRNAs that have been reported thus far are limited. In this study, we pursued to identify these miRNAs in Tet-on stable C2C12 cell line (C2C12/Runx2(Dox) subline). RESULTS: Microarray analysis revealed that alterations in miRNA expression occur with 54 miRNAs. Among these miRNAs, miR-690 was identified as a positive regulator of Runx2-induced osteogenic differentiation of C2C12 cells through gain- and loss-of-function assays. Expression of miR-690 is induced by Runx2, which binds directly to the putative promoter of mir-690 (Mirn690). The miR-690 proceeds to inhibit translation of the messenger RNA encoding the nuclear factor kappa B (NF-kappaB) subunit p65 whose overexpression inhibits Runx2-induced osteogenic differentiation of C2C12 cells. Interleukin-6 (IL-6), a downstream target of NF kappaB pathway, is upregulated by p65 overexpression but significantly downregulated during this differentiation process. Furthermore, overexpression of IL-6 impedes the expression of osteocalcin, a defined marker of late osteoblast differentiation. CONCLUSIONS: Together, our results suggest that the miR-690 transactivated by Runx2 acts as a positive regulator of Runx2-induced osteogenic differentiation by inactivating the NF-kappaB pathway via the downregulation of the subunit p65. PMID- 26877861 TI - Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives. AB - Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance. PMID- 26877866 TI - Characterization of a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features and their potential for in vivo cartilage regeneration strategies. AB - BACKGROUND: Progenitor cells display interesting features for tissue repair and reconstruction. In the last years, such cells have been identified in different cartilage types. In this study, we isolated a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features by outgrowth from human nasal septum cartilage. These putative progenitor cells were comparatively characterized with mesenchymal stem cells (MSC) and human nasal septum chondrocytes with respect to their cellular characteristics as well as surface marker profile using flow cytometric analyses. Differentiation capacity was evaluated on protein and gene expression levels. RESULTS: The migrative subpopulation differentiated into osteogenic and chondrogenic lineages with distinct differences to chondrocytes and MSC. Cells of the migrative subpopulation showed an intermediate surface marker profile positioned between MSC and chondrocytes. Significant differences were found for CD9, CD29, CD44, CD90, CD105 and CD106. The cells possessed a high migratory ability in a Boyden chamber assay and responded to chemotactic stimulation. To evaluate their potential use in tissue engineering applications, a decellularized septal cartilage matrix was either seeded with cells from the migrative subpopulation or chondrocytes. Matrix production was demonstrated immunohistochemically and verified on gene expression level. Along with secretion of matrix metalloproteinases, cells of the migrative subpopulation migrated faster into the collagen matrix than chondrocytes, while synthesis of cartilage specific matrix was comparable. CONCLUSIONS: Cells of the migrative subpopulation, due to their migratory characteristics, are a potential cell source for in vivo regeneration of nasal cartilage. The in vivo mobilization of nasal cartilage progenitor cells is envisioned to be the basis for in situ tissue engineering procedures, aiming at the use of unseeded biomaterials which are able to recruit local progenitor cells for cartilage regeneration. PMID- 26877867 TI - Misregulation of the proline rich homeodomain (PRH/HHEX) protein in cancer cells and its consequences for tumour growth and invasion. AB - The proline rich homeodomain protein (PRH), also known as haematopoietically expressed homeobox (HHEX), is an essential transcription factor in embryonic development and in the adult. The PRH protein forms oligomeric complexes that bind to tandemly repeated PRH recognition sequences within or at a distance from PRH-target genes and recruit a variety of PRH-interacting proteins. PRH can also bind to other transcription factors and co-regulate specific target genes either directly through DNA binding, or indirectly through effects on the activity of its partner proteins. In addition, like some other homeodomain proteins, PRH can regulate the translation of specific mRNAs. Altered PRH expression and altered PRH intracellular localisation, are associated with breast cancer, liver cancer and thyroid cancer and some subtypes of leukaemia. This is consistent with the involvement of multiple PRH-interacting proteins, including the oncoprotein c Myc, translation initiation factor 4E (eIF4E), and the promyelocytic leukaemia protein (PML), in the control of cell proliferation and cell survival. Similarly, multiple PRH target genes, including the genes encoding vascular endothelial growth factor (VEGF), VEGF receptors, Endoglin, and Goosecoid, are known to be important in the control of cell proliferation and cell survival and/or the regulation of cell migration and invasion. In this review, we summarise the evidence that implicates PRH in tumourigenesis and we review the data that suggests PRH levels could be useful in cancer prognosis and in the choice of treatment options. PMID- 26870320 TI - A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions. AB - The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity. Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium. PMID- 26870317 TI - YeATS - a tool suite for analyzing RNA-seq derived transcriptome identifies a highly transcribed putative extensin in heartwood/sapwood transition zone in black walnut. AB - The transcriptome provides a functional footprint of the genome by enumerating the molecular components of cells and tissues. The field of transcript discovery has been revolutionized through high-throughput mRNA sequencing (RNA-seq). Here, we present a methodology that replicates and improves existing methodologies, and implements a workflow for error estimation and correction followed by genome annotation and transcript abundance estimation for RNA-seq derived transcriptome sequences (YeATS - Yet Another Tool Suite for analyzing RNA-seq derived transcriptome). A unique feature of YeATS is the upfront determination of the errors in the sequencing or transcript assembly process by analyzing open reading frames of transcripts. YeATS identifies transcripts that have not been merged, result in broken open reading frames or contain long repeats as erroneous transcripts. We present the YeATS workflow using a representative sample of the transcriptome from the tissue at the heartwood/sapwood transition zone in black walnut. A novel feature of the transcriptome that emerged from our analysis was the identification of a highly abundant transcript that had no known homologous genes (GenBank accession: KT023102). The amino acid composition of the longest open reading frame of this gene classifies this as a putative extensin. Also, we corroborated the transcriptional abundance of proline-rich proteins, dehydrins, senescence-associated proteins, and the DNAJ family of chaperone proteins. Thus, YeATS presents a workflow for analyzing RNA-seq data with several innovative features that differentiate it from existing software. PMID- 26877870 TI - Influence of carbon nanomaterial defects on the formation of protein corona. AB - In any physiological media, carbon nanomaterials (CNM) strongly interact with biomolecules leading to the formation of biocorona, which subsequently dictate the physiological response and the fate of CNMs. Defects in CNMs play an important role not only in material properties but also in the determination of how materials interact at the nano-bio interface. In this article, we probed the influence of defect-induced hydrophilicity on the biocorona formation using micro Raman, photoluminescence, infrared spectroscopy, electrochemistry, and molecular dynamics simulations. Our results show that the interaction of proteins (albumin and fibrinogen) with CNMs is strongly influenced by charge-transfer between them, inducing protein unfolding which enhances conformational entropy and higher protein adsorption. PMID- 26877871 TI - Targeting bacterial biofilms via surface engineering of gold nanoparticles. AB - Bacterial biofilms are associated with persistent infections that are resistant to conventional antibiotics and substantially complicate patient care. Surface engineered nanoparticles represent a novel, unconventional approach for disruption of biofilms and targeting of bacterial pathogens. Herein, we describe the role of surface charge of gold nanoparticles (AuNPs) on biofilm disruption and bactericidal activity towards Staphylococcus aureus and Pseudomonas aeruginosa which are important ventilator associated pneumonia (VAP) pathogens. In addition, we study the toxicity of charged AuNPs on human bronchial epithelial cells. While 100% positively charged AuNP surface was uniformly toxic to both bacteria and epithelial cells, reducing the extent of positive charge on the AuNP surface at moderate concentrations prevented epithelial cell toxicity. Reducing surface charge was however also less effective in killing bacteria. Conversely, increasing AuNP concentration while maintaining a low level of positivity continued to be bactericidal and disrupt the bacterial biofilm and was less cytotoxic to epithelial cells. These initial in vitro studies suggest that modulation of AuNP surface charge could be used to balance effects on bacteria vs. airway cells in the context of VAP, but the therapeutic window in terms of concentration vs. surface positive charge may be limited. Additional factors such as hydrophobicity may need to be considered in order to design AuNPs with specific, beneficial effects on bacterial pathogens and their biofilms. PMID- 26877873 TI - Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy. AB - BACKGROUND: Already in the late 1960s and early 1970s, targeting of the "posterior subthalamic area (PSA)" was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR) guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT). METHODS: Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others' (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion. RESULTS: The mean ETRS score for all patients was 57.6 +/- 13.2 at baseline and 25.8 +/- 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up. CONCLUSIONS: CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally. PMID- 26877875 TI - Prognostic utility of plasma lactate measured between 24 and 48 h after initiation of early goal-directed therapy in the management of sepsis, severe sepsis, and septic shock. AB - BACKGROUND: Based on the proven efficacy of lactate in predicting mortality and morbidity in sepsis when measured early in the resuscitative protocol, our group hypothesized that this utility extends later in the course of care. This study sought to investigate the prognostic potential of plasma lactate clearance measured 24-48 h after the initiation of treatment for nonsurgical patients with sepsis, severe sepsis, and septic shock. METHODS: Plasma lactate values, measured 24-48 h after the initiation of treatment, were collected in nonsurgical septic, severe septic, and septic shock patients. The primary outcome was 30-day mortality, while secondary outcomes included requirements for vasopressors and boluses of intravenous fluids. Analysis of these three outcomes was performed while controlling for clinical severity as measured by Sequential Organ Failure Assessment (SOFA), renal dysfunction, and hepatic dysfunction. Lactate clearance was defined as the percent change in plasma lactate levels measured after 24-48 h of treatment from the plasma lactate level at initial presentation. RESULTS: Two hundred twenty-nine nonsurgical patients were divided into two groups, clearers (above median lactate clearance [31.6 %]) and nonclearers (below median lactate clearance [31.6 %]). The adjusted odds ratio of mortality in clearers compared to nonclearers was 0.39 (CI 0.20-0.76) (p = 0.006). For vasopressor requirement, the adjusted odds ratio was 0.41 (CI 0.21-0.79) in clearers compared to nonclearers (p = 0.008). For intravenous fluid bolus requirement, the adjusted odds ratio was 0.81 (CI 0.48-1.39) in clearers compared to nonclearers (p = 0.45). CONCLUSIONS: Lower plasma lactate clearance 24-48 h after the initiation of treatment is associated with higher 30-day mortality and requirements for vasopressors in nonsurgical septic patients and may be a useful noninvasive measurement for guiding late-sepsis treatment. Further investigation looking at mechanisms and therapeutic targets to improve lactate clearance in late sepsis may improve patient mortality and outcomes. PMID- 26877874 TI - RECQ helicases are deregulated in hematological malignancies in association with a prognostic value. AB - BACKGROUND: RECQ helicase family members act as guardians of the genome to assure proper DNA metabolism in response to genotoxic stress. Hematological malignancies are characterized by genomic instability that is possibly related to underlying defects in DNA repair of genomic stability maintenance. METHODS: We have investigated the expression of RECQ helicases in different hematological malignancies and in their normal counterparts using publicly available gene expression data. Furthermore, we explored whether RECQ helicases expression could be associated with tumor progression and prognosis. RESULTS: Expression of at least one RECQ helicase family member was found significantly deregulated in all hematological malignancies investigated when compared to their normal counterparts. In addition, RECQ helicase expression was associated with a prognostic value in acute myeloid leukemia, chronic lymphocytic leukemia, lymphoma and multiple myeloma. CONCLUSION: RECQ helicase expression is deregulated in hematological malignancies compared to their normal counterparts in association with a prognostic value. Deregulation of RECQ helicases appears to play a role in tumorigenesis and represent potent therapeutic targets for synthetic lethal approaches in hematological malignancies. PMID- 26877876 TI - The expression of embryonic globin mRNA in a severely anemic mouse model induced by treatment with nitrogen-containing bisphosphonate. AB - BACKGROUND: Mammalian erythropoiesis can be divided into two distinct types, primitive and definitive, in which new cells are derived from the yolk sac and hematopoietic stem cells, respectively. Primitive erythropoiesis occurs within a restricted period during embryogenesis. Primitive erythrocytes remain nucleated, and their hemoglobins are different from those in definitive erythrocytes. Embryonic type hemoglobin is expressed in adult animals under genetically abnormal condition, but its later expression has not been reported in genetically normal adult animals, even under anemic conditions. We previously reported that injecting animals with nitrogen-containing bisphosphonate (NBP) decreased erythropoiesis in bone marrow (BM). Here, we induced severe anemia in a mouse model by injecting NBP injection in combination with phenylhydrazine (PHZ), and then we analyzed erythropoiesis and the levels of different types of hemoglobin. METHODS: Splenectomized mice were treated with NBP to inhibit erythropoiesis in BM, and with PHZ to induce hemolytic anemia. We analyzed hematopoietic sites and peripheral blood using morphological and molecular biological methods. RESULTS: Combined treatment of splenectomized mice with NBP and PHZ induced critical anemia compared to treatment with PHZ alone, and numerous nucleated erythrocytes appeared in the peripheral blood. In the BM, immature CD71-positive erythroblasts were increased, and extramedullary erythropoiesis occurred in the liver. Furthermore, embryonic type globin mRNA was detected in both the BM and the liver. In peripheral blood, spots that did not correspond to control hemoglobin were observed in 2D electrophoresis. ChIP analyses showed that KLF1 and KLF2 bind to the promoter regions of beta-like globin. Wine-colored capsuled structures were unexpectedly observed in the abdominal cavity, and active erythropoiesis was also observed in these structures. CONCLUSION: These results indicate that primitive erythropoiesis occurs in adult mice to rescue critical anemia because primitive erythropoiesis does not require macrophages as stroma whereas macrophages play a pivotal role in definitive erythropoiesis even outside the medulla. The cells expressing embryonic hemoglobin in this study were similar to primitive erythrocytes, indicating the possibility that yolk sac-derived primitive erythroid cells may persist into adulthood in mice. PMID- 26877877 TI - Attitude, barriers and facilitators to practice-based research: cross-sectional survey of hospital pharmacists in Saudi Arabia. AB - BACKGROUND: Little is known about the perceived attitude, barriers and facilitators of Saudi Pharmacists about practice based research. We aimed to measure the attitude, barriers, and facilitators of Saudi hospital pharmacists towards pharmacy practice research. METHOD: A cross-sectional survey of hospital pharmacists (n = 216) working in King Abdulaziz Medical Cities in Central, Eastern and Western region hospitals was conducted during first week of September, 2013. The survey instrument comprised of six different sections that explored pharmacists previous participation in research, items regarding attitude, perception and willingness to participate, motivators, barriers, different areas of interest for doing research and patient demographics. Quantitative data collected was initially explored using frequency distribution, and descriptive analysis was carried out. Mann-Whitney U and independent samples t-test were used to explore the differences between the study variables. RESULTS: One hundred and eighty two pharmacists completed the survey yielding a response rate of 84 %. Fifty-nine percent of pharmacists have prior research experience. Pharmacists with research experience were more confident in reading and evaluating research papers (p = 0.01), and designing a research study (p = 0.001). Pharmacists with previous research experience were also more likely to participate in future research opportunities (p = 0.004) and were confident in their research skills (p = 0.003). No differences were observed about the perceived value of research, facilitators and barriers to participate in research, between pharmacists with prior research experience and pharmacists who have no prior experience to do research. CONCLUSION: Pharmacists in this study were unanimous about the importance of research but showed considerable differences in their confidence to carry out research. There is a need to provide additional support to enable Saudi pharmacists in conducting practice based research. PMID- 26877879 TI - Rising HbA1c in the presence of optimal glycaemic control as assessed by self monitoring - iron deficiency anaemia. AB - HbA1c can be affected by determinants other than glucose and an awareness of this is important to avoid unnecessary hypoglycaemia. PMID- 26877880 TI - A case series review of suicides associated with social media use in South Tyneside, England. PMID- 26877878 TI - The PI3K signaling pathway as a pharmacological target in Autism related disorders and Schizophrenia. AB - This review is focused in PI3K's involvement in two widespread mental disorders: Autism and Schizophrenia. A large body of evidence points to synaptic dysfunction as a cause of these diseases, either during the initial phases of brain synaptic circuit's development or later modulating synaptic function and plasticity. Autism related disorders and Schizophrenia are complex genetic conditions in which the identification of gene markers has proved difficult, although the existence of single-gene mutations with a high prevalence in both diseases offers insight into the role of the PI3K signaling pathway. In the brain, components of the PI3K pathway regulate synaptic formation and plasticity; thus, disruption of this pathway leads to synapse dysfunction and pathological behaviors. Here, we recapitulate recent evidences that demonstrate the imbalance of several PI3K elements as leading causes of Autism and Schizophrenia, together with the plausible new pharmacological paths targeting this signaling pathway. PMID- 26877882 TI - Clinical signs in functional (psychogenic) gait disorders: a brief survey. AB - Clinical signs are critical in ascertaining the functional nature of a gait disorder. Four signs of gait impairment have been documented in the course of examining patients with clinically definite functional (psychogenic) movement disorders: "huffing and puffing" during standing and walking, manipulation resistance dorsiflexion of the first toe, fixed plantar flexion and inversion, and marked discrepancy between ambulation with and without swivel chair assistance. While large studies are needed to ascertain their prevalence, sensitivity, and specificity, the identification of these signs may help elevate the diagnostic certainty of functional gait disorders. PMID- 26877881 TI - Delays and interruptions in the acute medical unit clerking process: an observational study. AB - OBJECTIVES: It is recommended that patients are seen within 4 h of arrival in Acute Medical Units in English hospitals. This study explored the frequency and nature of interruptions and delays potentially affecting the duration of the Acute Medical Unit admission process and the quality of care provided. DESIGN: The admission process was directly observed for patients admitted to the Acute Medical Unit over four one-week periods, November 2009 to April 2011. SETTING: UK teaching hospital Acute Medical Unit. PARTICIPANTS: Hospital staff n = 36. MAIN OUTCOME MEASURES: Patient waiting times, duration of clerking, number of interruptions and/or delays. RESULTS: Thirty-five doctors and one nurse practitioner were observed admitting 71 medical patients, 48/71 (68%) patients were clerked within 4 h of arrival. A delay and/or interruption affected 49/71 (69%) patients. Sixty-six interruptions were observed in 36/71 (51%) of admissions, of these 19/36 (53%) were interrupted more than once. The grade of doctor had no bearing on the frequency of interruption; however, clerking took significantly longer when interrupted; overall doctors grade ST1 and above were quicker at clerking than foundation doctors. Delays affected 31/71 (44%) of admissions, 14/31 (45%) involved X-rays or ECGs; other causes of delays included problems with equipment and computers. CONCLUSION: Interruptions and delays regularly occurred during the admission process in the study hospital which impacts adversely on patient experience and compliance with the recommended 4-h timeframe, further work is required to assess the impact on patient safety. Data obtained from this observational study were used to guide operational changes to improve the process. PMID- 26877883 TI - Agnosia for head tremor in essential tremor: prevalence and clinical correlates. AB - BACKGROUND: Lack of awareness of involuntary movements is a curious phenomenon in patients with certain movement disorders. An interesting anecdotal observation is that patients with essential tremor (ET) often seem unaware of their own head tremor. In the current study, we asked ET patients whether they were aware of head tremor while it was occurring on examination, thereby allowing us to gauge real-time awareness of their involuntary movement. METHODS: ET cases enrolled in an ongoing clinical research study at the Columbia University Medical Center (2009-2014). During a videotaped tremor examination, they were questioned about the presence of head tremor. True positives were cases who exhibited head tremor on examination and were aware of it; false negatives were cases who exhibited head tremor but were unaware of it. RESULTS: The 126 ET cases had a mean age of 72.6 +/- 12.4 years. Nineteen (48.7 %) of 39 cases with head tremor on examination did not report having head tremor at that moment. Even among cases with moderate or severe head tremor on examination, unawareness of head tremor was 45.5 %. We assessed the clinical correlates of unawareness of head tremor, comparing true positives to false negatives, and unawareness was correlated with older age, lower mental status test scores and several other clinical variables. CONCLUSIONS: Nearly one-half of ET cases with head tremor on examination were acutely unaware of their tremor. Whether such agnosia for tremor may be leveraged as a diagnostic feature of ET is a question for future clinical studies. PMID- 26877885 TI - Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. AB - Burkholderia pseudomallei, a highly pathogenic bacterium that causes melioidosis, is commonly found in soil in Southeast Asia and Northern Australia1,2. Melioidosis can be difficult to diagnose due to its diverse clinical manifestations and the inadequacy of conventional bacterial identification methods3. The bacterium is intrinsically resistant to a wide range of antimicrobials, and treatment with ineffective antimicrobials may result in case fatality rates (CFRs) exceeding 70%4,5. The importation of infected animals has, in the past, spread melioidosis to non-endemic areas6,7. The global distribution of B. pseudomallei and burden of melioidosis, however, remain poorly understood. Here, we map documented human and animal cases, and the presence of environmental B. pseudomallei, and combine this in a formal modelling framework8-10 to estimate the global burden of melioidosis. We estimate there to be 165,000 (95% credible interval 68,000-412,000) human melioidosis cases per year worldwide, of which 89,000 (36,000-227,000) die. Our estimates suggest that melioidosis is severely underreported in the 45 countries in which it is known to be endemic and that melioidosis is likely endemic in a further 34 countries which have never reported the disease. The large numbers of estimated cases and fatalities emphasise that the disease warrants renewed attention from public health officials and policy makers. PMID- 26877886 TI - Pharmacokinetic/Toxicity Properties of the New Anti-Staphylococcal Lead Compound SK-03-92. AB - Because of the potential of a new anti-staphylococcal lead compound SK-03-92 as a topical antibiotic, a patch, or an orally active drug, we sought to determine its safety profile and oral bioavailability. SK-03-92 had a high IC50 (125 MUg/ml) in vitro against several mammalian cell lines, and mice injected intraperiteonally at the highest dose did not exhibit gross toxicity (e.g. altered gait, ungroomed, significant weight loss). Single dose (100 MUg/g) pharmacokinetic (PK) analysis with formulated SK-03-92 showed that peak plasma concentration (1.64 MUg/ml) was achieved at 20-30 min. Oral relative bioavailability was 8%, and the drug half life was 20-30 min, demonstrating that SK-03-92 is likely not a candidate for oral delivery. Five-day and two-week PK analyses demonstrated that SK-03-92 plasma levels were low. Multi-dose analysis showed no gross adverse effects to the mice and a SK-03-92 peak plasma concentration of 2.12 MUg/ml with the presence of significant concentrations of breakdown products 15 min after dosing. SK-03-92 appeared to be very safe based on tissue culture and mouse gross toxicity determinations, but the peak plasma concentration suggests that a pro drug of SK-03-92 or preparation of analogs of SK-03-92 with greater bioavailability and longer half-lives are warranted. PMID- 26877884 TI - Bacterial vaginosis: a synthesis of the literature on etiology, prevalence, risk factors, and relationship with chlamydia and gonorrhea infections. AB - Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age. Since the initial work of Leopoldo in 1953 and Gardner and Dukes in 1955, researchers have not been able to identify the causative etiologic agent of BV. There is increasing evidence, however, that BV occurs when Lactobacillus spp., the predominant species in healthy vaginal flora, are replaced by anaerobic bacteria, such as Gardenella vaginalis, Mobiluncus curtisii, M. mulieris, other anaerobic bacteria and/or Mycoplasma hominis. Worldwide, it estimated that 20-30 % of women of reproductive age attending sexually transmitted infection (STI) clinics suffer from BV, and that its prevalence can be as high as 50-60 % in high risk populations (e.g., those who practice commercial sex work (CSW). Epidemiological data show that women are more likely to report BV if they: 1) have had a higher number of lifetime sexual partners; 2) are unmarried; 3) have engaged in their first intercourse at a younger age; 4) have engaged in CSW, and 5) practice regular douching. In the past decade, several studies have provided evidence on the contribution of sexual activity to BV. However, it is difficult to state that BV is a STI without being able to identify the etiologic agent. BV has also emerged as a public health problem due to its association with other STIs, including: human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). The most recent evidence on the association between BV and CT/NG infection comes from two secondary analyses of cohort data conducted among women attending STI clinics. Based on these studies, women with BV had a 1.8 and 1.9-fold increased risk for NG and CT infection, respectively. Taken together, BV is likely a risk factor or at least an important contributor to subsequent NG or CT infection in high-risk women. Additional research is required to determine whether this association is also present in other low-risk sexually active populations, such as among women in the US military. It is essential to conduct large scale cross-sectional or population-based case-control studies to investigate the role of BV as a risk factor for CT/NG infections. These studies could lead to the development of interventions aimed at reducing the burden associated with bacterial STIs worldwide. PMID- 26877887 TI - Empathy, justice, and moral behavior. AB - Empathy shapes the landscape of our social lives. It motivates prosocial and caregiving behaviors, plays a role in inhibiting aggression, and facilitates cooperation between members of a similar social group. Thus, empathy is often conceived as a driving motivation of moral behavior and justice, and as such, everyone would think that it should be cultivated. However, the relationships between empathy, morality, and justice are complex. We begin by explaining what the notion of empathy encompasses and then argue how sensitivity to others' needs has evolved in the context of parental care and group living. Next, we examine the multiple physiological, hormonal, and neural systems supporting empathy and its functions. One troubling but important corollary of this neuro-evolutionary model is that empathy produces social preferences that can conflict with fairness and justice. An understanding of the factors that mold our emotional response and caring motivation for others helps provide organizational principles and ultimately guides decision-making in medical ethics. PMID- 26877889 TI - "Heard It through the Grapevine": The Black Barbershop as a Source of Health Information. PMID- 26877888 TI - Targeting of Androgen Receptor Expression by Andro-miRs as Novel Adjunctive Therapeutics in Prostate Cancer. AB - Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3' untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of "andro-miRs" and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC. PMID- 26877890 TI - Immune-based Therapy Clinical Trials in Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality and continues to increase. Current standard of care for patients with HCC only provides limited therapeutic benefit. Development of innovative strategies is urgently needed. Experience with immunotherapy in HCC is quite early, but rapidly rise in the recent 15 years. Multifaceted immune-based approaches have shown efficacy in achieving disease regression, representing the most promising new treatment approach. Here, we classify the ongoing or completed clinical trials in HCC in terms of the immune strategies to be used and assess their clinical outcomes. The generated information may be helpful in the design of future immune-based therapies for achieving ideal tumor control and maximizing anti-tumor immunity. PMID- 26877891 TI - Dystonia Associated with Idiopathic Slow Orthostatic Tremor. AB - BACKGROUND: We aimed to characterize the clinical and electrophysiological features of patients with slow orthostatic tremor. CASE REPORT: The clinical and neurophysiological data of patients referred for lower limb tremor on standing were reviewed. Patients with symptomatic or primary orthostatic tremor were excluded. Eight patients were identified with idiopathic slow 4-8 Hz orthostatic tremor, which was associated with tremor and dystonia in cervical and upper limb musculature. Coherence analysis in two patients showed findings different to those seen in primary orthostatic tremor. DISCUSSION: Slow orthostatic tremor may be associated with dystonia and dystonic tremor. PMID- 26877892 TI - PEDOT Radical Polymer with Synergetic Redox and Electrical Properties. AB - The development of new redox polymers is being boosted by the increasing interest in the area of energy and health. The development of new polymers is needed to further advance new applications or improve the performance of actual devices such as batteries, supercapacitors, or drug delivery systems. Here we show the synthesis and characterization of a new polymer which combines the present most successful conjugated polymer backbone and the most successful redox active side group, i.e., poly(3,4-ethylenedioxythiophene) (PEDOT), and a nitroxide stable radical. First, a derivative of the 3,4-ethylenedioxythiophene (EDOT) molecule with side nitroxide stable radical group (TEMPO) was synthesized. The electrochemical polymerization of the PEDOT-TEMPO monomer was investigated in detail using cyclic voltammetry, potential step, and constant current methods. Monomer and polymer were characterized by NMR, FTIR, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), electron spin resonance (ESR) spectroscopy, elemental analysis, cyclic voltammetry, and four-point probe conductivity. The new PEDOT-TEMPO radical polymer combines the electronic conductivity of the conjugated polythiophene backbone and redox properties of the nitroxide group. As an example of application, this redox active polymer was used as a conductive binder in lithium ion batteries. Good cycling stability with high Coulombic efficiency and increased cyclability at different rates were obtained using this polymer as a replacement of two ingredients: conductive carbon additive and polymeric binders. PMID- 26877894 TI - THE STATE OF CANCER REHABILITATION. PMID- 26877893 TI - Obesity Education Strategies for Cancer Prevention in Women's Health. AB - Obesity is the cause of up to one-third of all cancers affecting women today, most notably endometrial, colon and breast cancer. Women's health providers are poised to advise women on obesity's link to cancer development, but often lack resources or training to provide appropriate counseling. Here, we review obesity's role in increasing the risk of several common reproductive system conditions faced by women, including polycystic ovarian syndrome, infertility, gynecologic surgical complications, and pregnancy complications. These events can be used as teachable moments to help frame the discussion of weight management and promote cancer prevention. We also review national guidelines and existing tangible weight-loss strategies that can be employed within the outpatient women's health setting to help women achieve weight loss goals and affect cancer prevention. PMID- 26877896 TI - Natural radioactivity levels in soils, rocks and water at a mining concession of Perseus gold mine and surrounding towns in Central Region of Ghana. AB - Levels of naturally occurring radioactive materials prior to processing of gold ore within and around the new eastern concession area of Perseus Mining (Ghana) Limited were carried out to ascertain the baseline radioactivity levels. The study was based on situ measurements of external gamma dose rate at 1 m above ground level as well as laboratory analysis by direct gamma spectrometry to quantify the radionuclides of interest namely; (238)U, (232)Th and (40)K in soil, rock, ore samples and gross alpha/beta analysis in water samples. The average absorbed dose rate in air at 1 m above sampling point using a radiation survey metre was determined to be 0.08 +/- 0.02 MUGyh(-1) with a corresponding average annual effective dose calculated to be 0.093 +/- 0.028 mSv. The average activity concentrations of (238)U, (232)Th, and (40)K in the soil, rock, and ore samples were 65.1 +/- 2.2, 71.8 +/- 2.2 and 1168.3 Bqkg(-1) respectively resulting in an average annual effective dose of 0.91 +/- 0.32 mSv. The average Radium equivalent activity value was 257.8 +/- 62.4 Bqkg(-1) in the range of 136.6-340.2 Bqkg(-1). The average values of external and internal indices were 0.7 +/- 0.2 and 0.9 +/- 0.2 respectively. The average gross alpha and gross beta activity concentrations in the water samples were determined to be 0.0032 +/- 0.0024 and 0.0338 +/- 0.0083 Bql(-1) respectively. The total annual effective dose from the pathways considered for this study (gamma ray from the soil, rock and ore samples as well as doses determined from the gross alpha/beta activity concentration in water samples) was calculated to be 0.918 mSv. The results obtained in this study shows that the radiation levels are within the natural background radiation levels found in literature and compare well with similar studies for other countries and the total annual effective dose is below the ICRP recommended level of 1 mSv for public exposure control. PMID- 26877895 TI - Relation between self-recalled childhood physical activity and adult physical activity: The women's health initiative. AB - BACKGROUND: Evidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity. METHODS: 48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 14, and 15 - 19. RESULTS: In this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood. CONCLUSIONS: It is important for researchers to understand the influence of adult characteristics on reported childhood physical activity. PMID- 26877897 TI - Ewald expansions of a class of zeta-functions. AB - The incomplete gamma function expansion for the perturbed Epstein zeta function is known as Ewald expansion. In this paper we state a special case of the main formula in Kanemitsu and Tsukada (Contributions to the theory of zeta-functions: the modular relation supremacy. World Scientific, Singapore, 2014) whose specifications will give Ewald expansions in the H-function hierarchy. An Ewald expansion for us are given by [Formula: see text] or its variants. We shall treat the case of zeta functions which satisfy functional equation with a single gamma factor which includes both the Riemann as well as the Hecke type of functional equations and unify them in Theorem 2. This result reveals the H-function hierarchy: the confluent hypergeometric function series entailing the Ewald expansions. Further we show that some special cases of this theorem entails various well known results, e.g., Bochner-Chandrasekharan theorem, Atkinson Berndt theorem etc. PMID- 26877898 TI - Note on fractional Mellin transform and applications. AB - In this article, we define the fractional Mellin transform by using Riemann Liouville fractional integral operator and Caputo fractional derivative of order [Formula: see text] and study some of their properties. Further, some properties are extended to fractional way for Mellin transform. PMID- 26877899 TI - Evaluating a learning management system for blended learning in Greek higher education. AB - This paper focuses on the usage of a learning management system in an educational institution for higher education in Greece. More specifically, the paper examines the literature on the use of different learning management systems for blended learning in higher education in Greek Universities and Technological Educational Institutions and reviews the advantages and disadvantages. Moreover, the paper describes the usage of the Open eClass platform in a Technological Educational Institution, TEI of Ionian Islands, and the effort to improve the educational material by organizing it and adding video-lectures. The platform has been evaluated by the students of the TEI of Ionian Islands based on six dimensions: namely student, teacher, course, technology, system design, and environmental dimension. The results of this evaluation revealed that Open eClass has been successfully used for blended learning in the TEI of Ionian Islands. Despite the instructors' initial worries about students' lack of participation in their courses if their educational material was made available online and especially in video lectures; blended learning did not reduce physical presence of the students in the classroom. Instead it was only used as a supplementary tool that helps students to study further, watch missed lectures, etc. PMID- 26877900 TI - Robustness of the Quadratic Discriminant Function to correlated and uncorrelated normal training samples. AB - This study investigates the asymptotic performance of the Quadratic Discriminant Function (QDF) under correlated and uncorrelated normal training samples. This paper specifically examines the effect of correlation, uncorrelation considering different sample size ratios, number of variables and varying group centroid separators ([Formula: see text], [Formula: see text]) on classification accuracy of the QDF using simulated data from three populations ([Formula: see text]). The three populations differs with respect to their mean vector and covariance matrices. The results show the correlated normal distribution exhibits high coefficient of variation as [Formula: see text] increased. The QDF performed better when the training samples were correlated than when they were under uncorrelated normal distribution. The QDF performed better resulting in the reduction in misclassification error rates as group centroid separator increases with non increasing sample size under correlated training samples. PMID- 26877901 TI - On synchronal algorithm for fixed point and variational inequality problems in hilbert spaces. AB - The aim of this article is to expand and generalize some approximation methods proposed by Tian and Di (J Fixed Point Appl, 2011. doi:10.1186/1687-1812-21) to the class of [Formula: see text]-total asymptotically strict pseudocontraction to solve the fixed point problem as well as variational inequality problem in the frame work of Hilbert space. Further, the results presented in this paper extend, improve and also generalize several known results in the literature . PMID- 26877902 TI - Impact of data layouts on the efficiency of GPU-accelerated IDW interpolation. AB - This paper focuses on evaluating the impact of different data layouts on the computational efficiency of GPU-accelerated Inverse Distance Weighting (IDW) interpolation algorithm. First we redesign and improve our previous GPU implementation that was performed by exploiting the feature of CUDA dynamic parallelism (CDP). Then we implement three versions of GPU implementations, i.e., the naive version, the tiled version, and the improved CDP version, based upon five data layouts, including the Structure of Arrays (SoA), the Array of Structures (AoS), the Array of aligned Structures (AoaS), the Structure of Arrays of aligned Structures (SoAoS), and the Hybrid layout. We also carry out several groups of experimental tests to evaluate the impact. Experimental results show that: the layouts AoS and AoaS achieve better performance than the layout SoA for both the naive version and tiled version, while the layout SoA is the best choice for the improved CDP version. We also observe that: for the two combined data layouts (the SoAoS and the Hybrid), there are no notable performance gains when compared to other three basic layouts. We recommend that: in practical applications, the layout AoaS is the best choice since the tiled version is the fastest one among three versions. The source code of all implementations are publicly available. PMID- 26877903 TI - Management of peri-implantitis: a systematic review, 2010-2015. AB - Peri-implantitis or Periimplantitis is characterized as an inflammatory reaction that affects the hard and soft tissue, which results in loss of supporting bone and pocket formation surrounding the functioning osseointegrated implant. This review aimed to evaluate the effectiveness of surgical and non-surgical treatment of peri-implantitis. The data sources used was PubMed. Searches of this database were restricted to English language publications from January 2010 to June 2015. All Randomized Controlled Trials describing the treatments of peri-implantitis of human studies with a follow up of at least 6 months were included. Eligibility and quality were assessed and two reviewers extracted the data. Data extraction comprised of type, intensity provider, and location of the intervention. A total of 20 publications were included (10 involving surgical and 10 involving non surgical mechanical procedure). The non-surgical approach involves the mechanical surface debridement using carbon or titanium currettes, laser light, and antibiotics whereas, surgical approach involves implantoplasty, elevation of mucoperiosteal flap and removal of peri-inflammatory granulation tissue followed by surface decontamination and bone grafting. This study reveals that non surgical therapy tends to remove only the local irritant from the peri implantitis surface with or without some additional adjunctive therapies agents or device. Hence, non-surgical therapy is not helpful in osseous defect. Surgical therapy in combination with osseous resective or regenerative approach removes the residual sub-gingival deposits additionally reducing the peri-implantitis pocket. Although there is no specific recommendation for the treatment of peri implantitis, surgical therapy in combination with osseous resective or regenerative approach showed the positive outcome. PMID- 26877904 TI - Codimension-one bifurcation and stability analysis in an immunosuppressive infection model. AB - One of the important medical problems is infectious diseases such as HIV and hepatitis which annually causes the death of many people. So it is important to study infectious diseases parametric models. In this paper, we investigate differential equations system of HIV and hepatitis (with delay and without delay) from the stability and codimension-one bifurcation point of view. We show that their dynamical behaviour will change when the parameters vary. We prove that this model has a saddle-node bifurcation and transcritical bifurcation when the delay parameter is absent. Also by using the center manifold theory, we show that the delay model has a saddle-node bifurcation. PMID- 26877905 TI - Daily microhabitat shifting of solitarious-phase Desert locust adults: implications for meaningful population monitoring. AB - The Desert locust Schistocerca gregaria is a major world pest that causes substantial agricultural and economic damage. Effective pest control relies on effective monitoring, which requires knowledge of locust microhabitat selection. Yet little is known about microhabitat selection of solitarious adult locusts in the field. We conducted field surveys to investigate fine-scale diel temporal and spatial distributions of solitarious adults in the Sahara Desert in Mauritania, a major breeding and recession area. We found that solitarious adults moved among different, specific microhabitats throughout the 24-h period in a cyclical manner. At night, they roosted in trees, moved to the ground to feed shortly after dawn, sheltered in low vegetation during the hot midday, and returned to the ground in the late afternoon. Hence, they switched microhabitats and plant species throughout each day. These cyclical daily movements among diverse microhabitats and specific plant species were correlated with time of day, light intensity, temperature, humidity, and specific plant species, and may relate to anti-predator defence, thermoregulation, and feeding. The present study suggests that locust monitoring should be adjusted, based on time of day, locust age, phase state and relative abundance of specific plant species. For example, we recommend surveying ground after morning and trees at night, for solitarious adults, when at low density. PMID- 26877906 TI - Vertical profile of atmospheric conductivity that matches Schumann resonance observations. AB - We introduce the vertical profile of atmospheric conductivity in the range from 2 to 98 km. The propagation constant of extremely low frequency (ELF) radio waves was computed for this profile by using the full wave solution. A high correspondence is demonstrated of the data thus obtained to the conventional standard heuristic model of ELF propagation constant derived from the Schumann resonance records performed all over the world. We also suggest the conductivity profiles for the ambient day and ambient night conditions. The full wave solution technique was applied for obtaining the corresponding frequency dependence of propagation constant relevant to these profiles. By using these propagation constants, we computed the power spectra of Schumann resonance in the vertical electric field component for the uniform global distribution of thunderstorms and demonstrate their close similarity in all the models. We also demonstrate a strong correspondence between the wave attenuation rate obtained for these conductivity profiles and the measured ones by using the ELF radio transmissions. PMID- 26877908 TI - Reaction of hydroxylated naphtoquinones/antraquinones with pentafluoropyridine. AB - In this study, the reaction of pentafluoropyridine with hydroxylated naphtoquinones and hydroxylated antraquinones was investigated under basic conditions in DMF. One or two hydroxyl group in naphtoquinones and antraquinones react with pentafluoropyridine to give mono and di-tetrafluoropyridyl naphtoquinones/antraquinones. All the compounds were characterized using (1)H, (13)C and (19)F-NMR spectroscopy. PMID- 26877909 TI - A Boosting Algorithm for Estimating Generalized Propensity Scores with Continuous Treatments. AB - In this article, we study the causal inference problem with a continuous treatment variable using propensity score-based methods. For a continuous treatment, the generalized propensity score is defined as the conditional density of the treatment-level given covariates (confounders). The dose-response function is then estimated by inverse probability weighting, where the weights are calculated from the estimated propensity scores. When the dimension of the covariates is large, the traditional nonparametric density estimation suffers from the curse of dimensionality. Some researchers have suggested a two-step estimation procedure by first modeling the mean function. In this study, we suggest a boosting algorithm to estimate the mean function of the treatment given covariates. In boosting, an important tuning parameter is the number of trees to be generated, which essentially determines the trade-off between bias and variance of the causal estimator. We propose a criterion called average absolute correlation coefficient (AACC) to determine the optimal number of trees. Simulation results show that the proposed approach performs better than a simple linear approximation or L2 boosting. The proposed methodology is also illustrated through the Early Dieting in Girls study, which examines the influence of mothers' overall weight concern on daughters' dieting behavior. PMID- 26877907 TI - Patterns in target-directed breast cancer research. AB - We undertake an analysis of ongoing BC targeted therapy trials registered to CT.gov to describe patterns of ongoing clinical research, highlight gaps in current research programs and identify ways of optimizing ongoing initiatives. A search of clinicaltrials.gov was conducted on September 4, 2013 to identify ongoing randomized phase II and III trials of targeted therapies in BC. A total of 280 trials were analyzed, the majority conducted in either human epidermal growth factor receptor 2 (HER2)-positive (n = 79, 28.2 %) or hormone receptor (HR)-positive (n = 104, 37.1 %) populations. Less than half of all trials were conducted in populations selected to match the agent under investigation (n = 126, 45 %). HER2-directed therapy is the single most investigated class of targeted agents (n = 73, 26.1 %), but trials investigating anti-angiogenic agents are also common (n = 49, 17.5 %). The most common new classes of agents under investigation in HR-positive and triple negative (TN)/BRCA-positive disease, are non-receptor protein kinase-inhibitors (n = 12; 11.5 %) and poly (ADP-ribose) polymerase inhibitors (n = 6; 30 %), respectively. The majority of regimens combine new targeted agents with either chemotherapy (n = 164, 58.6 %) or endocrine therapy (n = 113, 40.4 %); a total of 8 trials (2.8 %) investigated peptide-drug conjugates. The most frequently utilized end-points were pathological complete response in the neo-adjuvant setting (n = 36, 52.9 %) and time-to-event end-points in the adjuvant and advanced settings (77.3 and 72.6 %, respectively). Our findings suggest a need for more target-matched agent development, maintenance of a value-based focus in research and a need for the clinical development of agents to treat TN/BRCA-positive and HR-positive BC. PMID- 26877910 TI - Planar Photonic Crystal Biosensor for Quantitative Label-Free Cell Attachment Microscopy. AB - In this study, a planar-surface photonic crystal (PC) biosensor for quantitative, kinetic, label-free imaging of cell-surface interactions is demonstrated. The planar biosensor surface eliminates external stimuli to the cells caused by substrate topography to more accurately reflect smooth surface environment encountered by many cell types in vitro. Here, a fabrication approach that combines nanoreplica molding and a horizontal dipping process is used to planarize the surface of the PC biosensor. The planar PC biosensor maintains a high detection sensitivity that enables the monitoring of live cell-substrate interactions with spatial resolution sufficient for observing intracellular attachment strength gradients and the extensions of filopodia from the cell body. The evolution of cell morphology during the attachment and spreading process of 3T3 fibroblast cells is compared between planar and grating-structured PC biosensors. The planar surface effectively eliminates the directionally biased cellular attachment behaviors that are observed on the grating-structured surface. This work represents an important step forward in the development of label-free techniques for observing cellular processes without unintended external environmental modulation. PMID- 26877911 TI - The Challenge of Pulmonary Nontuberculous Mycobacterial Infection. AB - The incidence of nontuberculous mycobacterial (NTM) lung disease is increasing. Current treatment strategies are largely based on expert opinion. The lack of randomized clinical trials to inform treatment leave clinicians with many questions regarding the most effective and safe regimens. The risk-benefit ratio of therapy is often thought to favor observation given the chronic nature of the disease, multiple long-term antibiotics recommended for therapy, side effects associated with treatment, and perceived lack of efficacious therapies. PMID- 26877912 TI - Is VEGF a new therapeutic target for hypertension in chronic kidney disease? PMID- 26877913 TI - Immunologic monitoring in kidney transplant recipients. AB - Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work up of renal allograft dysfunction-an update. Curr Opin Nephrol Hypertens 8:723 728, 1999). A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the "drug level" era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients. PMID- 26877914 TI - Postdialysis serum sodium changes and systolic blood pressure in patients undergoing online hemodiafiltration and high-flux hemodialysis. AB - BACKGROUND: Because hemodiafiltration (HDF) involves large amounts of ultra filtration and substitution fluid infusion, its effects on serum electrolytes may be different from those of hemodialysis (HD). Serum sodium and blood pressures were compared between patients undergoing online HDF and high-flux HD (HFHD). METHODS: Thirty-two of 101 patients on HFHD switched voluntarily to online HDF. Their pre- and postdialysis serum measurements were compared with those of the remaining 69 HFHD patients. RESULTS: Online HDF patients had lower pre- and postdialysis systolic blood pressures (SBPs) than HFHD patients (predialysis, 136+/-21 vs. 145+/-19 mmHg, P<0.05; postdialysis, 129+/-22 vs. 142+/-25 mmHg, P<0.05). Pre- and postdialysis serum sodium concentrations were not significantly different between online HDF and HFHD (predialysis, 138+/-2 vs. 137+/-3 mEq/L; postdialysis, 134+/-2 vs. 134+/-2 mEq/L). However, the change in serum sodium concentration after dialysis was greater in online HDF than HFHD patients (-3.7+/ 2.2 vs. -2.5+/-2.8 mEq/L, P<0.05). The change in serum sodium concentration was correlated with postdialysis SBP (r=0.304, P<0.005) and pulse pressure (r=0.299, P<0.005). Predialysis SBP (r = 0.317, P<0.005) and pulse pressure (r=0.324, P=0.001) were also correlated with the postdialysis serum sodium change. CONCLUSION: Compared with HFHD, online HDF has a greater serum sodium lowering effect. This might contribute to the ability of online HDF to stabilize both pre- and postdialysis SBP. PMID- 26877915 TI - Decreased serum level and increased urinary excretion of vascular endothelial growth factor-C in patients with chronic kidney disease. AB - BACKGROUND: Interstitial tonicity increases vascular endothelial growth factor-C (VEGF-C), a lymphangiogenic factor in salt-induced hypertension. Therefore, it can be assumed that changes of serum VEGF-C level may be associated with increasing blood pressure. However, there is no report about the changes of serum VEGF-C levels in patients with chronic kidney disease (CKD). The aims of this study were to investigate the changes of serum and urine VEGF-C levels in patients with CKD stage 3-4 and to evaluate the relationship between blood pressure and serum VEGF-C levels in the patients with CKD stage 5 and hemodialysis. METHODS: Glomerular filtration rate (GFR) was assessed by the Modification of Diet in Renal Disease equation. Blood pressure and VEGF-C levels (serum and urine) were measured by enzyme-linked immunosorbent assay (ELISA) in nine patients with stage 3-4 CKD, 41 hemodialysis patients, and eight healthy individuals. RESULTS: The median serum level of VEGF-C in patients with stage 3-4 CKD and stage 5 hemodialysis significantly decreased in comparison with healthy individuals. Urinary VEGF-C excretion increased in patients with stage 3-4 CKD compared with healthy control patients. For 41 hemodialysis patients, the serum level of VEGF-C in patients with stage 1 or stage 2 hypertension with hemodialysis did not significantly increase when compared with prehypertension hemodialysis patients. CONCLUSION: We demonstrated that circulating levels of VEGF-C were decreased in patients with CKD, and the decrease of VEGF-C in patients with stage 3-4 CKD coincided with an increase in the urinary excretion of VEGF-C. PMID- 26877916 TI - Obstructive uropathy after inguinal herniorrhaphy with a mesh in a renal transplant patient. AB - A 67-year-old male renal transplant patient presented with a right inguinal bulging mass, and was diagnosed with a right indirect inguinal hernia. The day following inguinal herniorrhaphy, serum creatinine became elevated. The patient was oliguric and had abdominal pain on the first day after inguinal herniorrhaphy with a mesh. We diagnosed him with acute renal failure and subsequently performed acute hemodialysis. The kidney computed tomography showed hydronephroureter, with distal ureter obstruction. With urgent percutaneous nephrostomy, we were able to relieve the obstructive uropathy with distal ureteral stenosis. Subsequently, hernia repair was performed with removal of the mesh, followed by the antegrade ureteral stent insertion. Renal function was recovered after ureteral stent insertion. This case shows that acute renal failure can occur due to ureteral obstruction, complicated by an inguinal hernia repair, and this can be successfully treated with percutaneous nephrostomy and inguinal hernia repair with mesh removal. PMID- 26877917 TI - Colchicine-induced myoneuropathy in a cyclosporine-treated renal transplant recipient. AB - Colchicine is a relatively safe medication that is widely used for both prevention and treatment of gout attack. However, serious adverse events, including myoneuropathy and multiorgan failure, have been reported. We report a case of colchicine-induced myoneuropathy in a female kidney transplant recipient who had been taking cyclosporine. She developed gastrointestinal discomfort and paresthesia 5 days after the initiation of colchicine. She showed signs of myoneuropathy, and hepatic and renal injury. Colchicine toxicity was suspected, and colchicine was discontinued. Her symptoms and laboratory findings improved gradually. Literature was reviewed for previous reports of colchicine-induced myoneuropathy in solid organ transplant recipients. PMID- 26877919 TI - Successful antibiotic treatment of Pseudomonas stutzeri-induced peritonitis without peritoneal dialysis catheter removal in continuous ambulatory peritoneal dialysis. AB - Pseudomonas stutzeri is a Gram-negative, rod-shaped, motile, single polar flagellated, soil bacterium that was first isolated from human spinal fluid and is widely distributed in the environment. It was isolated as an uncommon opportunistic pathogen from humans, and a few cases of P. stutzeri-induced peritonitis have been reported in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Catheter removal with antibiotic treatment is generally recommended because peritonitis by Pseudomonas species is commonly associated with catheter-related infection. Here, we describe the first case of P. stutzeri-induced peritonitis in an 82-year-old woman in Korea. She had received two antipseudomonal antibiotics, an aminoglycoside (isepamicin, Yuhan corporation, Seoul, Korea) and a fluoroquinolone (ciprofloxacin), and was successfully treated without removal of the CAPD catheter. PMID- 26877918 TI - A case of peritoneal dialysis-associated peritonitis caused by Sphingomonas paucimobilis. AB - Sphingomonas paucimobilis is an aerobic Gram-negative bacillus found in soil and water. Knowledge regarding the role of this infectious agent is limited because it is rarely isolated from human material. Furthermore, it is an unusual pathogen in cases of peritoneal dialysis (PD)-associated peritonitis. The clinical courses and outcomes of peritonitis caused by S. paucimobilis are variable. Whereas some patients were cured with appropriate antibiotic therapy, others required catheter removal. Cases of PD-associated peritonitis caused by S. paucimobilis have been reported worldwide, and there was a case report of coinfection with S. paucimobilis and Chryseobacterium indologenes in Korea. However, there has been no case caused by S. paucimobilis as a single pathogen. We report a case of PD associated peritonitis due to S. paucimobilis in which the patient recovered after catheter removal. PMID- 26877920 TI - Hemorrhagic cystitis with massive bleeding from nontyphoidal Salmonella infection: A case report. AB - Hemorrhagic cystitis is defined by lower urinary tract symptoms that include dysuria, hematuria, and hemorrhage and is caused by viral or bacterial infection or chemotherapeutic agents. Reports of hemorrhagic cystitis caused by non typhoidal salmonella (NTS) are extremely rare. We report a case of a 41-year-old man with hemorrhagic cystitis from NTS that caused massive bleeding and shock. The patient was hospitalized for uncontrolled diabetes and obstructive uropathy related to severe cystitis. A urine culture was positive for group D NTS. This case demonstrated that hemorrhagic cystitis in a patient with a risk factor such as diabetes can be a manifestation of local extra-intestinal NTS infection. PMID- 26877921 TI - Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy. AB - A 37-year-old man was referred to Division of Nephrology for a new renal cystic lesion that was found on ultrasonography. Four years prior to presentation, a percutaneous renal biopsy had been performed. Computed tomography scan showed a 4.4-cm-sized renal artery pseudoaneurysm in the left kidney. Selective renal angiography revealed a pseudoaneurysm in the left lower pole of the kidney. The renal pseudoaneurysm was successfully embolized with coil. Follow-up Doppler ultrasonography showed no internal blood flow into the aneurysmal sac. His renal function remained stable after coil embolization. PMID- 26877922 TI - Urine output before the initiation of CRRT and mortality. PMID- 26877923 TI - Regulation of aquaporin-2 in the kidney: A molecular mechanism of body-water homeostasis. AB - The kidneys play a key role in the homeostasis of body water and electrolyte balance. Aquaporin-2 (AQP2) is the vasopressin-regulated water-channel protein expressed at the connecting tubule and collecting duct, and plays a key role in urine concentration and body-water homeostasis through short-term and long-term regulation of collecting duct water permeability. The signaling transduction pathways resulting in the AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, including AQP2 phosphorylation, RhoA phosphorylation, actin depolymerization, and calcium mobilization, and the changes of AQP2 abundance in water-balance disorders have been extensively studied. Dysregulation of AQP2 has been shown to be importantly associated with a number of clinical conditions characterized by body-water balance disturbances, including hereditary nephrogenic diabetes insipidus (NDI), lithium-induced NDI, electrolytes disturbance, acute and chronic renal failure, ureteral obstruction, nephrotic syndrome, congestive heart failure, and hepatic cirrhosis. Recent studies exploiting omics technology further demonstrated the comprehensive vasopressin signaling pathways in the collecting ducts. Taken together, these studies elucidate the underlying molecular mechanisms of body-water homeostasis and provide the basis for the treatment of body-water balance disorders. PMID- 26877924 TI - Primary glomerulonephritis: A review of important recent discoveries. AB - The publication of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines on the treatment of glomerular diseases in 2012 marked a milestone in this field, as it is the first time that comprehensive guidelines are provided for such disease entities. The current review focuses on major findings, both pathogenesis related and clinical, in the primary glomerulonephritis that have been made after the guidelines came into effect. PMID- 26877925 TI - Clinical manifestations of IgA nephropathy combined with thin glomerular basement membrane nephropathy in children. AB - BACKGROUND: Immunoglobulin A nephropathy (IgAN) and thin glomerular basement membrane nephropathy (TBMN) are the most common causes of persistent hematuria during childhood. The objective of this study is to determine the difference in clinical features and laboratory findings between pediatric patients with IgA deposited TBMN and IgAN alone. METHODS: Between January 2000 and March 2009, 95 children were diagnosed with IgAN by renal biopsy. Clinical features and laboratory findings of patients with isolated IgAN and with IgAN plus TBMN were compared; the children diagnosed with IgAN were compared to 127 children who had been diagnosed with TBMN alone during the same period. RESULTS: There were 71 (74.7%) of a total 95 patients that were diagnosed with isolated IgAN (Group1); in 24 (25.3%) of the 95 patients IgAN was combined with TBMN (Group 2). There was marked difference in the gender distribution between Group 2 and isolated TBMN patients. The degree of proteinuria and pathologic severity was higher in Group 1 compared with Group 2. Gross hematuria was present in both groups. There were no distinguishing features in the other laboratory parameters. CONCLUSION: Patients with both IgAN and TBMN seem to have similar clinical features to patients with isolated IgAN; however, the latter tend to have better pathologic and laboratory findings, compared to the patients with IgAN alone. PMID- 26877926 TI - Nondiabetic kidney diseases in type 2 diabetic patients. AB - BACKGROUND: The aim of this study was to evaluate the clinical characteristics of nondiabetic nephropathy in type 2 diabetes mellitus patients and to find a clinical significance of renal biopsy and immunosuppressive treatment in such a patient. METHODS: Renal biopsy results, clinical parameters, and renal outcomes were analyzed in 75 diabetic patients who underwent kidney biopsy at Chungnam National University Hospital from January 1994 to December 2010. RESULTS: The three most common reasons for renal biopsy were nephrotic range proteinuria (44%), proteinuria without diabetic retinopathy (20%), and unexplained decline in renal function (20.0%). Ten patients (13.3%) had only diabetic nephropathy (Group I); 11 patients (14.7%) had diabetic nephropathy with superimposed nondiabetic nephropathy (Group II); and 54 patients (72%) had only nondiabetic nephropathy (Group III). Membranous nephropathy (23.1%), IgA nephropathy (21.5%), and acute tubulointerstitial nephritis (15.4%) were the three most common nondiabetic nephropathies. Group III had shorter duration of diabetes and lesser diabetic retinopathy than Groups I and II (P=0.008). Group II had the lowest baseline estimated glomerular filtration rate (P=0.002), with the greatest proportion of renal deterioration during follow-up (median 38.0 months, P<0.0001). The patients who were treated with intensive method showed better renal outcomes (odds ratio 4.931; P=0.01). Absence of diabetic retinopathy was associated with favorable renal outcome in intensive treatment group (odds ratio 0.114; P=0.032). CONCLUSION: Renal biopsy should be recommended for type 2 diabetic patients with atypical nephropathy because a considerable number of these patients may have nondiabetic nephropathies. And intensive treatment including corticosteroid or immunosuppressants could be recommended for type 2 diabetic patients with nondiabetic nephropathy, especially if the patients do not have diabetic retinopathy. PMID- 26877927 TI - De novo glomerulitis associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: A single-center experience. AB - BACKGROUND: Nephrotic syndrome (NS) and proteinuria are uncommon, often unrecognized manifestations of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). Only a few isolated case reports and case series involving smaller number of patients who developed NS after HSCT have been published. METHODS: We reviewed the renal histopathological examination findings and clinical records of 15 patients who developed proteinuria after HSCT at Seoul and Yeouido St. Mary's Hospital (Seoul, Korea). We also measured the anti-PLA2R antibodies (M-type phospholipase A2 receptor) in the serum samples from the seven patients at the time of renal biopsy. RESULTS: All patients had GVHD. The most common indication for biopsy was proteinuria (>1 g/day), with nine patients having nephrotic range proteinuria. The most common histopathological finding was membranous nephropathy (MN; n = 12). Other findings were membranoproliferative glomerulonephritis, C1q nephropathy, and diabetic nephropathy. Eleven patients were treated with immunosuppressive agents, and three patients were treated only with angiotensin II receptor blocker. The overall response rate, including complete remission (urinary protein level <0.3 g/day) and partial remission (urinary protein level = 0.31-3.4 g/day), was 73%. The mean follow-up period was 26 months, and none of the patients developed end stage renal disease. All of the seven patients with MN had negative findings for anti-PLA2R antibodies, measured using an enzyme-linked immunosorbent assay kit. CONCLUSION: In this study the findings of 15 renal biopsies were analyzed and to our knowledge this is the largest clinicopathological study of GVHD-related biopsy-proven nephropathy. Approximately 80% of the patients were MN and 73% responded either partially or completely to immunosuppressive treatment. Currently, there is an increase in the incidence of GVHD-mediated renal disease, and therefore, renal biopsy is essential for diagnosing the nephropathy and preventing the progression of renal disease. PMID- 26877929 TI - Membranous glomerulonephritis in a patient with myelodysplastic syndrome refractory cytopenia with multilineage dysplasia. AB - A 74-year-old woman presented with edema in the lower extremities. Laboratory tests revealed anemia, thrombocytopenia, hypoalbuminemia, hypercholesterolemia, and nephrotic-range proteinuria. Myelodysplastic syndrome-refractory cytopenia with multilineage dysplasia (MDS-RCMD) was confirmed by bone marrow biopsy. Renal biopsy demonstrated membranous glomerulonephritis (MGN), stage I. Based on these clinicopathologic results, she was diagnosed as having MGN with MDS-RCMD. This is a rare case report of MGN in a parient with MDS-RCMD featuring nephrotic syndrome. PMID- 26877928 TI - The effect of on-line hemodiafiltration on heart rate variability in end-stage renal disease. AB - BACKGROUND: The autonomic nervous system plays a central role in the maintenance of hemodynamic stability. Cardiac autonomic dysfunction may result in serious complications, such as sudden cardiac death. Heart rate variability (HRV) is significantly reduced in patients undergoing chronic hemodialysis (HD). The aim of this study was to evaluate the effect of on-line hemodiafiltration (OL-HDF) on the autonomic nervous system in chronic HD patients. METHODS: Forty chronic HD patients were prospectively studied. The participants were divided into conventional HD and OL-HDF groups. They received regular high-flux HD or OL-HDF for 4-hour sessions, three times a week. Time-and frequency-domain measures of the 24-hour HRV were analyzed during the interdialytic period prior to postdilution OL-HDF and every 6 months for 24 months. The 7-year survival was also evaluated. RESULTS: Among the 40 participants, 15 patients in the HD group and 11 patients in the OL-HDF group completed the study. There was no difference in the baseline characteristics. After 24 months of treatment, beta2 microglobulin concentration decreased (from 33.4+/-15.2 mg/dL to 28.4+/-6.2 mg/dL, P =0.02) in the OL-HDF group, while there was no change in the HD group. In the HRV analysis, the frequency-domain HRV parameters increased significantly compared with baseline in the OL-HDF group [natural logarithmic high frequency (lnHF), 3.15+/-3.36 ms(2) vs. 4.42+/-3.81 ms(2); ln low frequency (LF), 3.56+/ 3.17 ms(2) vs. 4.78+/-3.99 ms(2); ln very low frequency (VLF), 4.90+/-4.62 ms(2) vs. 6.38+/-5.54 ms(2); LF/HF ratio, 1.4+/-0.4 vs. 2.5+/-0.1]. The survival rate was similar between the groups. CONCLUSION: This study shows that OL-HDF improved autonomic nervous system dysfunction in chronic HD patients. PMID- 26877931 TI - Determining when to measure vascular access flow ...that may not be enough. PMID- 26877930 TI - Two cases of idiopathic membranous nephropathy treated with rituximab. AB - Idiopathic membranous nephropathy is a common cause of nephrotic syndrome, and has been reported as a cause of idiopathic primary glomerulonephropathy in up to 90% of patients. However, the treatment options remain controversial. We report two cases of idiopathic membranous nephropathy that were treated with rituximab. A 54-year-old man and a 64-year old man were admitted for rituximab therapy. They had previously been treated with combinations of immunosuppressive agents including cyclophosphamide, cyclosporine, mycophenolate, and steroids. However, the patients' heavy proteinuria was not resolved. Both patients received rituximab therapy, 2 weeks apart. After several months of follow-up and a second round of rituximab treatment for each patient, their proteinuria decreased and partial remission of disease was achieved in both patients. PMID- 26877932 TI - Hidden pathology of kidney disease after liver transplantation. PMID- 26877933 TI - Proinflammatory CD14(+)CD16(+) monocytes are associated with vascular stiffness in predialysis patients with chronic kidney disease. AB - BACKGROUND: Chronic inflammation is frequently noted in patients with chronic kidney disease (CKD) and contributes to the development and progression of cardiovascular diseases. Monocytes are heterogeneous populations of cells, and they can be divided into subtypes with different phenotypes and functions based on CD14 and CD16 positivity. This study examined whether the proinflammatory CD14(+)CD16(+) monocyte subset expands in predialysis CKD patients, and also whether the expansion of these cells is closely associated with systemic inflammation and cardiovascular risk factors. METHODS: The percentages of proinflammatory CD14(+)CD16(+) monocytes were analyzed in 111 predialysis CKD patients using a flow cytometer, and they were compared with brachial-ankle pulse wave velocity as well as the cytokine plasma levels and other clinical parameters. RESULTS: The proportion of CD14(+)CD16(+) monocytes was significantly higher in patients with advanced stages of CKD than in patients with the early stages. Interleukin-6 levels were also high in patients with advanced stages of CKD. The expansion of CD14(+)CD16(+) monocytes showed significant positive correlations with the high-sensitive C-reactive protein levels, and negative correlations with the levels of serum albumin, hemoglobin, and 25(OH)-vitamin D. In addition, the expansion of CD14(+)CD16(+) monocytes was an independent factor correlated with brachial-ankle pulse wave velocity in diabetic CKD patients. CONCLUSION: Expansion of the proinflammatory CD14(+)CD16(+) monocyte subset partially accounts for chronic inflammation, malnutrition, and atherosclerosis in CKD. PMID- 26877934 TI - Clinical usefulness of kidney biopsy in liver transplant recipients with renal impairment. AB - BACKGROUND: Chronic kidney disease is a common complication after liver transplantation. In this study, we analyzed the results of kidney biopsy in liver transplantation recipients with renal impairment. METHODS: Between 1999 and 2012, 544 liver transplants were performed at our hospital. We retrospectively analyzed the clinical and histological data of 10 liver transplantation recipients referred for kidney biopsy. RESULTS: The biopsies were performed at a median of 24.5 months (range, 3-73 months) after liver transplantation. The serum creatinine level was 1.81+/-0.5 mg/dL at the time of kidney biopsy. There were no immediate complications. The most common diagnosis was glomerulonephritis (GN), such as immunoglobulin A nephropathy (n=4), mesangial proliferative GN (n=1), focal proliferative GN (n=1), and membranous GN (n=1). Typical calcineurin inhibitor (CNI)-induced nephrotoxicity was detected in three cases (30%). Chronic tissue changes such as glomerulosclerosis, interstitial fibrosis, and tubular atrophy were present in 90%, 80%, and 80% of cases, respectively, and mesangial proliferation was detected in 40% of cases. We began treatment for renal impairment based on the result of kidney biopsy; for example, angiotensin receptor blockers or steroids were prescribed for GN, and the CNI dose was reduced for CNI nephrotoxicity. As a result, eight of 10 patients showed improvement in glomerular filtration rate, but two progressed to end-stage renal disease. CONCLUSION: Kidney biopsy is a safe and effective method for determining the cause of renal impairment after liver transplantation. Management of patients based on the result of kidney biopsy may improve renal outcomes. PMID- 26877935 TI - Resistive index as a predictor of acute kidney injury caused by an angiotensin converting enzyme inhibitor or angiotensin II receptor blocker in chronic kidney disease patients. AB - BACKGROUND: Angiotensin converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) may induce acute kidney injury (AKI). The aim of this study was to evaluate the role of the resistive index (RI), which reflects renal artery resistance on renal duplex ultrasonography, as a predictor of AKI in chronic kidney disease (CKD) patients who are prescribed an ACE inhibitor or ARB. METHODS: We screened 105 CKD patients evaluated with renal duplex ultrasonography from 2008 to 2012. We excluded patients not treated with ACE inhibitor or ARB and diagnosed with renal artery stenosis. Finally, we retrospectively analyzed the medical records of 54 patients. AKI was defined as increased serum creatinine by >30% compared with baseline after starting ACE inhibitor or ARB treatment. RESULTS: The mean age of the patients was 60.5+/-13.0 years, serum creatinine level was 1.85+/-0.85 mg/dL and 22.2% of the patients had AKI after the use of an ACE inhibitor or ARB. The RI (P=0.006) and the percentages of patients with diabetes (P=0.008) and using diuretics (P=0.046) were higher in the AKI group. The area under the receiver operating characteristics curve for the prediction of AKI was 0.736 (95% confidence interval=0.587-0.885, P=0.013), and RI>=0.80 predicted AKI with 83.3% sensitivity and 61.9% specificity. In the multivariate analysis, RI>=0.80 was an independent prognostic factor [Exp (B)=8.03, 95% confidence interval=1.14-56.74, P=0.037] for AKI. CONCLUSION: RI>=0.80 on the renal duplex ultrasonography may be a helpful predictor for AKI in CKD patients who are prescribed an ACE inhibitor or ARB. PMID- 26877936 TI - Correlation between periodontitis and chronic kidney disease in Korean adults. AB - BACKGROUND: Periodontitis and chronic kidney disease (CKD) are important health issues; however, the association between periodontitis and CKD markers, especially in Korean adults, remains elusive. METHODS: Data on 15,729 Korean adults were obtained from the Korean National Health and Nutritional Examination Surveys IV and V. The CKD markers included a decreased estimated glomerular filtration rate (eGFR;<60 mL/min/1.73 m(2)), proteinuria, and hematuria. Odds ratios (ORs) and 95% confidence intervals were measured using stepwise multivariate logistic regression analyses for CKD markers based on the presence of periodontitis. RESULTS: Patients with periodontitis had greater unadjusted ORs for CKD markers compared to those without periodontitis, as follows: decreased eGFR, 4.07 (3.11-5.33); proteinuria, 2.12 (1.48-3.05); and hematuria, 1.25 (1.13 1.39, all P<0.001). Periodontitis was a significant predictor of decreased eGFR independent of all covariates [1.39 (1.03-1.89), P=0.034]. However, the effect of periodontitis on decreased eGFR seemed to be affected by hypertension and diabetes mellitus. Periodontitis was not an independent predictor of proteinuria; the significance disappeared after adjusting for hypertension and diabetes mellitus. Periodontitis was significantly correlated with hematuria, leading to similar ORs regardless of the adjustment for covariates [1.29 (1.15-1.46), P<0.001]. CONCLUSION: This study confirms the correlation between periodontitis and CKD markers, including decreased eGFR, proteinuria, and hematuria in Korean adults. PMID- 26877937 TI - High serum C-reactive protein level predicts mortality in patients with stage 3 chronic kidney disease or higher and diabetic foot infections. AB - BACKGROUND: Diabetic patients are predisposed to foot infections because of vascular insufficiency and peripheral neuropathy. Diabetic foot infection is a common cause of mortality and lower extremity amputations (LEAs) in patients with chronic kidney disease (CKD). We evaluated the risk factors for mortality and LEAs in patients with stage 3 CKD or higher with diabetic foot infections. METHODS: We retrospectively evaluated a cohort of 105 CKD patients with diabetic foot infections between July 1998 and December 2011. We reviewed their demographic characteristics and laboratory parameters to evaluate the risk factors for mortality and amputations at 24 weeks after diagnosis of a diabetic foot infection. RESULTS: The mortality of the 105 enrolled CKD patients was 21% at 24 weeks after the diagnosis of a diabetic foot infection. Cox proportional regression analyses revealed that age 60 years or older [odds ratio (OR) 3.03, 95% confidence interval (CI) = 1.02-9.02, P = 0.047] and initial serum C-reactive protein (CRP) level >= 3 mg/dL (OR 3.97, 95% CI = 1.17-13.43, P = 0.027) were independent risk factors for mortality at 24 weeks. Twenty-four patients (23%) underwent LEAs. On Cox proportional regression analyses, peripheral vascular disease (OR=4.49, 95% CI=1.98-10.17, P=0.01) and cerebrovascular accident (OR 2.42, 95% CI=1.09-5.39, P=0.03) were independently associated with LEAs. CONCLUSION: This study showed that age and serum CRP level, were independent risk factors for mortality at 24 weeks in patients with stage 3-5 CKD with diabetic foot infections. Peripheral vascular disease and cerebrovascular accident were significantly associated with LEAs. PMID- 26877939 TI - Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis in a patient with a single functioning kidney. AB - Retroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue around the abdominal aorta and ureteral entrapment in most cases. Idiopathic RPF is frequently reported in association with autoimmune diseases; however, there have been few reports of idiopathic RPF associated with Hashimoto's thyroiditis. Here, we report a case of idiopathic RPF with Hashimoto's thyroiditis in a patient with a single functioning kidney, which was successfully treated by corticosteroid therapy and transient intraureteral stent insertion with a double-J catheter. PMID- 26877938 TI - Features of atherosclerosis in hemodialysis patients. AB - BACKGROUND: Cardiovascular disease is the main cause of mortality in dialysis patients. Carotid intima-media thickness (CIMT) is used as a surrogate marker of early atherosclerosis. Atherosclerosis can cause vascular access failure. The purpose of this study was to define the clinical features of atherosclerosis in hemodialysis patients based on CIMT and to define the relationship between CIMT and access failure. METHODS: In this cross-sectional study, the CIMT of 60 patients on hemodialysis was examined using B-mode Doppler ultrasonography between May 2012 and November 2012. Carotid atherosclerosis was defined as a CIMT>=0.9 mm or the incidence of atherosclerotic plaques. RESULTS: The patients' mean age was 54.5+/-10.6 years, and 60% of the patients were male. The CIMT was 0.81+/-0.47 mm (range, 0.35-2.50 mm). The group with atherosclerosis was characterized by older age compared with those without atherosclerosis. Patients with atherosclerosis showed much shorter durations of access patency than their counterparts in the nonatherosclerosis group (hazard ratio, 2.822; 95% confidence interval, 1.113-7.156; P=0.029). Moreover, being overweight was associated with a 2.47-fold (95% confidence interval, 1.101-5.548) increased primary access failure. CONCLUSION: This study shows that atherosclerosis is associated with older age. Patients who are overweight and have atherosclerosis may have shortened access patency. PMID- 26877940 TI - Blue toe syndrome treated with sympathectomy in a patient with acute renal failure caused by cholesterol embolization. AB - Blue toe syndrome is the most frequent manifestation of tissue ischemia caused by cholesterol embolization (CE), which can lead to amputation of affected lower extremities, if severe. However, any effective treatment is lacking. We experienced a case of spontaneously presenting blue toe syndrome and concomitant acute renal failure in a patient with multiple atherosclerotic risk factors. CE was confirmed by renal biopsy. Despite medical treatment including prostaglandin therapy and narcotics, the toe lesion progressed to gangrene with worsening ischemic pain. Therefore, we performed lumbar sympathectomy, which provided dramatic pain relief as well as an adequate blood flow to the ischemic lower extremities, resulting in healing of the gangrenous lesion and avoiding toe amputation. This is the first reported case of a patient with intractable ischemic toe syndrome caused by CE that was treated successfully by sympathectomy. Our observations suggest that sympathectomy may be beneficial in some patients with CE-associated blue toe syndrome. PMID- 26877942 TI - IgA nephropathy combined with thin basement membrane nephropathy in children. PMID- 26877943 TI - Oxidative stress, the capo of endothelial dysfunction in chronic renovascular hypertension. PMID- 26877941 TI - A case of scrub typhus requiring maintenance hemodialysis. AB - Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report. PMID- 26877945 TI - Renal replacement therapy in Korea, 2012. AB - The Korean Society of Nephrology (KSN) launched the official end-stage renal disease (ESRD) patient registry in 1985, and an Internet online registry program was opened in 2001 and revised in 2013. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The status of renal replacement therapy in Korea at the end of 2012 is described in the following. The total number of ESRD patients was 70,211 at the end of 2012, which included 48,531 hemodialysis (HD) patients, 7,552 peritoneal dialysis (PD) patients, and 14,128 functioning kidney transplant (KT) patients. The prevalence of ESRD was 1,353.3 patients per million population (PMP), and the distribution of renal replacement therapy among ESRD patients was as follows: HD, 69.1%; PD, 10.8%; and KT, 20.2%. The number of new ESRD patients in 2012 was 11,742 (HD, 8,811; PD, 923; and KT, 1,738; the incidence rate was 221.1 PMP). The primary causes of ESRD were diabetic nephropathy (50.6%), hypertensive nephrosclerosis (18.5%), and chronic glomerulonephritis (18.1%). The mean urea reduction ratio was 67.9% in male and 74.1% in female HD patients. The mean Kt/V was 1.382 in male and 1.652 in female HD patients. The 5-year survival rates of male and female dialysis patients were 70.6% and 73.5%, respectively. PMID- 26877944 TI - Treatment of phosphate retention: The earlier the better? AB - Over the last 15 years, our knowledge and understanding of the underlying mechanisms involved in the regulation of calcium and phosphate homeostasis in chronic kidney disease have advanced dramatically. Contrary to general opinion in the 20(th) century that moderate hypercalcemia and hyperphosphatemia were acceptable in treating secondary hyperparathyroidism, the calcium and phosphate load is increasingly perceived to be a major trigger of vascular and soft tissue calcification. The current treatment options are discussed in view of historical developments and the expectations of the foreseeable future, focusing on the early treatment of hyperphosphatemia. At present, we lack indisputable evidence that active intervention using currently available drugs is of benefit to patients in chronic kidney disease stages 3 and 4. PMID- 26877946 TI - Effects of oxidative stress on endothelial modulation of contractions in aorta from renal hypertensive rats. AB - BACKGROUND: Endothelial dysfunction is linked to exaggerated production of superoxide anions. This study was conducted to examine the effects of oxidative stress on endothelial modulation of contractions in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: The 2K1C hypertension was induced by clipping the left renal artery; age-matched rats receiving sham treatment served as controls. Thoracic aortae were isolated and mounted in tissue baths for measurement of isometric tension. RESULTS: Norepinephrine-induced contraction was augmented by the removal of the endothelium, which was more pronounced in sham rats than in 2K1C rats. Nomega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide production, had a similar augmenting effect. Vitamin C inhibited the contraction in aortic rings with intact endothelium from 2K1C rats but not from sham rats. The contraction was also suppressed by treatment with diphenyleneiodonium or apocynin, inhibitors of nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase, in the aortae with intact endothelium from 2K1C rats but not in those from sham rats. Superoxide anions generated by xanthine oxidase/hypoxanthine enhanced the contraction in the aortae with intact endothelium from sham rats, but had no effect in 2K1C rats. Enhanced contractile responses to norepinephrine by xanthine oxidase/hypoxanthine in sham rats were reversed by vitamin C. CONCLUSION: These results suggest that the effect on endothelial modulation of endothelium-derived nitric oxide is impaired in 2K1C hypertension. The impairment is, at least in part, related to increased production of superoxide anions by NADH/NADPH oxidase. PMID- 26877947 TI - Diabetic conditions modulate the adenosine monophosphate-activated protein kinase of podocytes. AB - BACKGROUND: Adenosine monophosphate-activated protein kinases (AMPKs), as a sensor of cellular energy status, have been known to play an important role in the pathophysiology of diabetes and its complications. Because AMPKs are known to be expressed in podocytes, it is possible that podocyte AMPKs could be an important contributing factor in the development of diabetic proteinuria. We investigated the roles of AMPKs in the pathological changes in podocytes induced by high-glucose (HG) and advanced glycosylation end products (AGEs) in diabetic proteinuria. METHODS: We prepared streptozotocin-induced diabetic renal tissues and cultured rat and mouse podocytes under diabetic conditions with AMPK modulating agents. The changes in AMPKalpha were analyzed with confocal imaging and Western blotting under the following conditions: (1) normal glucose (5mM, =control); (2) HG (30mM); (3) AGE-added; or (4) HG plus AGE-added. RESULTS: The density of glomerularphospho-AMPKalpha in experimental diabetic nephropathy decreased as a function of the diabetic duration. Diabetic conditions including HG and AGE changed the localization of phospho-AMPKalpha from peripheral cytoplasm to internal cytoplasm and peri- and intranuclear areas in podocytes. HG reduced the AMPKalpha (Thr172) phosphorylation of rat podocytes, and similarly, AGEs reduced the AMPKalpha (Thr172) phosphorylation of mouse podocytes. The distributional and quantitative changes in phospho-AMPKalpha caused by diabetic conditions were preventable using AMPK activators, metformin, and 5 aminoimidazole-4-carboxamide-1beta-riboside. CONCLUSION: We suggest that diabetic conditions induce the relocation and suppression of podocyte AMPKalpha, which would be a suggestive mechanism in diabetic podocyte injury. PMID- 26877948 TI - Effects of Toll-like receptor antagonist 4,5-dihydro-3-phenyl-5-isoxasole acetic acid on the progression of kidney disease in mice on a high-fat diet. AB - BACKGROUND: Obesity-related metabolic disorders are closely associated with inflammation induced by innate immunity. Toll-like receptors (TLRs) play a pivotal role in the innate immune system by activating proinflammatory signaling pathways. GIT27 (4,5-dihydro-3-phenyl-5-isoxasole acetic acid) is an active immunomodulatory agent that primarily targets macrophages and inhibits secretion of tumor necrosis factor alpha [as well as interleukin (IL)-1beta, IL-10, and interferon gamma]. However, the effect of TLR antagonist on kidney diseases has rarely been reported. We investigated whether the TLR antagonist GIT27 has beneficial effects on the progression of kidney disease in obese mice on a high fat diet (HFD). METHODS: Six-week-old male C57BL/6 mice were divided into three groups: mice fed with normal chow diet (N=4); mice fed with a HFD (60% of total calories from fat, 5.5% from soybean oil, and 54.5% from lard, N=4); and GIT27 treated mice fed with a HFD (N=7). RESULTS: Glucose intolerance, oxidative stress, and lipid abnormalities in HFD mice were improved by GIT27 treatment. In addition, GIT27 treatment decreased the urinary excretion of albumin and protein in obesity-related kidney disease, urinary oxidative stress markers, and inflammatory cytokine levels. This treatment inhibited the expression of proinflammatory cytokines in the kidneys and adipose tissue, and improved extracellular matrix expansion and tubulointerstitial fibrosis in obesity-related kidney disease. CONCLUSION: TLR inhibition by administering GIT27 improved metabolic parameters. GIT27 ameliorates abnormalities of lipid metabolism and may have renoprotective effects on obesity-related kidney disease through its anti inflammatory properties. PMID- 26877949 TI - Comparison of glomerular filtration rates calculated by different serum cystatin C-based equations in patients with chronic kidney disease. AB - BACKGROUND: We aimed to evaluate the performance of serum cystatin C-based equations in calculating the glomerular filtration rate (GFR) in patients with varying stages of chronic kidney disease (CKD). METHODS: Serum cystatin C and creatinine levels were measured in 615 CKD patients. The CKD stage was determined by the creatinine-based estimated GFR (eGFR) equation using the four-variable abbreviated Modification of Diet in Renal Disease equation suggested by the Kidney Disease Outcome Quality Initiative with the addition of a coefficient applicable to Korean populations (K-aMDRD). In each CKD stage, the ratio of serum cystatin C to creatinine was calculated and six different cystatin C-based equations were used to estimate GFR. Cystatin C-based eGFR and aMDRD eGFR values were compared using the paired t test, Pearson correlation test, and the Bland Altman plot. RESULTS: The mean age of patients was 53.21+/-14.45 years; of the 615 patients, 346 were male. The serum cystatin C-to-creatinine ratio was inversely correlated with the CKD stage. Compared with the K-aMDRD values, the results of the Hoek, Filler, and Le Bricon's cystatin C-based eGFR equations were lower in CKD Stages 1-3 and higher in Stages 4 and 5. However, the results of the Orebro-cystatin (Gentian) equation [GFR=100/ScytC (mL/minute/1.73 m(2)) - 14] were similar to those of the K-aMDRD equation in CKD Stages 4 and 5 (15.44+/-9.45 vs. 15.17+/-9.05 mL/minute/1.73 m(2), respectively; P=0.722; bias=0.27+/-8.87). CONCLUSION: The eGFRs obtained from the six cystatin C-based equations differed widely. Therefore, further studies are required to determine the most accurate equation to estimate GFR in Koreans with CKD. PMID- 26877950 TI - Serum calcium and phosphorus levels in patients undergoing maintenance hemodialysis: A multicentre study in Korea. AB - BACKGROUND: In many countries, nephrologists follow clinical practice guidelines for mineral bone disorders to control secondary hyperparathyroidism (SHPT) associated with abnormal serum calcium (Ca) and phosphorus (P) levels in patients undergoing maintenance hemodialysis (MHD). The Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines have long been used in Korea, and this study was undertaken to investigate the current status of serum Ca and P control in MHD patients. METHODS: Data were collected from a total of 1,018 patients undergoing MHD without intercurrent illness, in 17 hemodialysis centers throughout the country. Serum levels of Ca, P, and intact parathyroid hormone (iPTH) were measured over 1 year, and the average values were retrospectively analyzed. RESULTS: Serum levels of Ca, P, and the Ca*P product were 9.1+/-0.7 mg/dL, 5.3+/ 1.4 mg/dL, and 48.0+/-13.6 mg(2)/dL(2), respectively. However, the percentages of patients with Ca, P, and Ca * P product levels within the KDOQI guideline ranges were 58.7%, 51.0%, and 70.7%, respectively. Of the 1,018 patients, 270 (26.5%) had iPTH >300 pg/mL (uncontrolled SHPT), whereas 435 patients (42.7%) showed iPTH <150 pg/mL. Patients with uncontrolled SHPT had significantly higher values of serum Ca, P, and Ca*P product than those with iPTH <=300 pg/mL. CONCLUSION: Despite the current clinical practice guidelines, SHPT seems to be inadequately controlled in many MHD patients. Uncontrolled SHPT was associated with higher levels of serum Ca, P, and Ca * P product, suggestive of the importance of SHPT management. PMID- 26877952 TI - Non-diabetic nephropathy in diabetics. PMID- 26877951 TI - Cat-induced Pasteurella multocida peritonitis in continuous ambulatory peritoneal dialysis. AB - Pasteurella multocida is a zoonotic pathogen found in the oral cavities of both domestic and wild animals. Although P. multocida has been involved in a wide range of human diseases, only a limited number of studies on P. multocida peritonitis in patients undergoing peritoneal dialysis (PD) had been carried out. We herein present the case of P. multocida peritonitis in a patient undergoing continuous ambulatory PD, which is believed to have resulted from contact with cats. We suggest that patients undergoing PD and having domestic animals at home should be educated about the possible transmission of the infection from the animals; in addition, these patients should also maintain a high level of personal hygiene. PMID- 26877953 TI - Experimental evidence that preexisting chronic kidney disease is a risk factor for acute kidney injury. PMID- 26877954 TI - Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease. AB - The primary cilium of renal epithelia acts as a transducer of extracellular stimuli. Polycystin (PC)1 is the protein encoded by the PKD1 gene that is responsible for the most common and severe form of autosomal dominant polycystic kidney disease (ADPKD). PC1 forms a complex with PC2 via their respective carboxy terminal tails. Both proteins are expressed in the primary cilia. Mutations in either gene affect the normal architecture of renal tubules, giving rise to ADPKD. PC1 has been proposed as a receptor that modulates calcium signals via the PC2 channel protein. The effect of PC1 dosage has been described as the rate limiting modulator of cystic disease. Reduced levels of PC1 or disruption of the balance in PC1/PC2 level can lead to the clinical features of ADPKD, without complete inactivation. Recent data show that ADPKD resulting from inactivation of polycystins can be markedly slowed if structurally intact cilia are also disrupted at the same time. Despite the fact that no single model or mechanism from these has been able to describe exclusively the pathogenesis of cystic kidney disease, these findings suggest the existence of a novel cilia-dependent, cyst-promoting pathway that is normally repressed by polycystin function. The results enable us to rethink our current understanding of genetics and cilia signaling pathways of ADPKD. PMID- 26877955 TI - Development of intestinal ischemia/reperfusion-induced acute kidney injury in rats with or without chronic kidney disease: Cytokine/chemokine response and effect of alpha-melanocyte-stimulating hormone. AB - BACKGROUND: The primary aim of the study was to investigate the cytokine/chemokine response in the kidney, lung, and liver following acute kidney injury (AKI). The secondary aim was to test whether alpha-melanocyte-stimulating hormone (alpha-MSH) could prevent a reduction in organ function, and attenuate the inflammatory cytokine/chemokine response within the kidney, lung, and liver following AKI in rats with or without preexisting chronic kidney disease (CKD). METHODS: A two-stage animal model, in which AKI was induced in rats with preexisting CKD, induced by 5/6 nephrectomy (Nx), was used. Six weeks later, AKI was induced by intestinal ischemia and reperfusion (IIR). Sham procedures [S(Nx) and S(IIR)] were also performed. RESULTS: Increasing levels of serum creatinine (sCr) demonstrated progressive development of CKD in response to Nx, and following IIR sCr levels increased further significantly, except in the S(Nx) group treated with alpha-MSH. However, no significant differences in the fractional increase in sCr were observed between any of the groups exposed to IIR. In kidney, lung, and liver tissue the levels of interleukin (IL)-1beta were significantly higher in rats undergoing IIR when compared to the S(IIR) and control rats. The same pattern was observed for the chemokine monocyte chemoattractant protein (MCP)-1 in lung and liver tissue. Furthermore, kidney IL 1beta and RANTES levels were significantly increased after IIR in the Nx rats compared to the S(Nx) rats. CONCLUSION: Both the functional parameters and the cytokine/chemokine response are as dramatic when AKI is superimposed onto CKD as onto non-CKD. No convincing protective effect of alpha-MSH was detected. PMID- 26877956 TI - Excess mortality among patients on dialysis: Comparison with the general population in Korea. AB - BACKGROUND: Although patients with end-stage renal disease (ESRD) experience excess mortality compared with the general population, the standardized mortality ratio (SMR) for Korean patients on dialysis has not yet been investigated. In this study, we evaluated the SMR among all Korean ESRD patients on maintenance dialysis in 2009 and 2010, and compared it according to age categories, sex, and dialysis modality. METHODS: We used data from all patients on maintenance dialysis between January 1, 2009 and December 31, 2010 in Korea using the database of the Korean Health Insurance Review and Assessment Service, and the SMR was determined by calculating of the ratio between the number of actual deaths and expected deaths. RESULTS: A total of 45,568 patients in 2009 and 48,170 patients in 2010 were included in the analysis. The overall age- and sex adjusted SMR was 10.3 [95% confidence interval (CI), 10.0-10.6] in 2009 and 10.9 (95% CI, 10.7-11.2) in 2010. The SMR for females was much higher than for males. The SMR gradually decreased with increasing age groups. The overall SMR for maintenance hemodialysis patients was lower than that of peritoneal dialysis patients. CONCLUSION: The SMR among Korean ESRD patients is likely to be higher than in other countries. Further evaluation is needed to attempt to improve the outcomes. PMID- 26877957 TI - The association between mortality and abdominal aortic calcification and relation between its progression and serum calcium concentration in chronic hemodialysis patients. AB - BACKGROUND: The composite summary score (range, 0-24) of abdominal aortic calcification (AAC) devised by Kauppila et al is a simple method of assessing AAC severity. However, few studies have been conducted to determine an optimal AAC cutoff score for the prediction of mortality or to investigate the relation between mineral metabolism and AAC progression using the scoring system. METHODS: The medical records of 112 patients on hemodialysis who had undergone simple lateral lumbar radiography every 6 months from August 2009 were reviewed. Patients were followed until November 2012, and the relationship between the degree of AAC at baseline and mortality was evaluated. In addition, the relationship between the progression of AAC and serum concentrations of calcium and phosphate was evaluated in the 75 patients who were successfully followed until November 2012. RESULTS: The mean AAC score at baseline was 5.5+/-4.8, and the cutoff calcification score for the prediction of mortality was 7.75 (sensitivity=61%, specificity=81%). Patients were allocated to Group A (baseline total calcification score <=8.0, n=85) or Group B (baseline total calcification score>8.0, n=27), and multivariate analysis showed that Group B was an independent risk factor of all-cause mortality and cardiovascular events. Of the 75 patients successfully followed, 51 showed AAC progression (Group 1) and 24 showed no change or improvement (Group 2). Group 1 was found to have significantly higher mean serum corrected calcium levels during the 2(nd) year and 3(rd) year of follow-up than Group 2. Furthermore, repeated-measures analysis of variance showed higher monthly corrected calcium concentrations (P=0.099) and mean corrected calcium levels during the 1(st) year, 2(nd) year, and 3(rd) year of follow-up (P=0.062) in Group 1, but without statistical significance. The cutoff values of mean corrected calcium of the 2(nd) year and 3(rd) year for the prediction of AAC progression during follow-up years were 8.96 mg/dL and 9.45 mg/dL, respectively. Serum phosphate levels and corrected calcium*phosphate values were similar in Groups 1 and 2. CONCLUSION: Patients with an AAC score of>8 at baseline seem to be at higher risk of mortality during follow-up. Of the serum variables examined, such as corrected calcium, phosphate, and corrected calcium*phosphate, corrected calcium was found to be marginally associated with AAC progression. However, a larger-scale prospective study is required to confirm our findings. PMID- 26877958 TI - Thrombotic microangiopathy resulting from neglected blood pressure control. AB - Hypertensive nephrosclerosis is usually associated with chronic hypertension, which increases the risk of progressive renal disease. Among the causes of malignant hypertension, thrombotic microangiopathy is complicated and is associated with renal dysfunction at the time of diagnosis. In this case, a young man with hypertension presented with renal failure and thrombocytopenia in the emergency department. This case emphasizes the importance of early recognition of renal failure and thrombocytopenia among patients with uncontrolled hypertension. PMID- 26877959 TI - A case of reninoma with variant angina. AB - Reninoma is a tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia because of hypersecretion of renin. We present a case of a 29-year-old female patient with reninoma and concomitant variant angina. The patient had uncontrolled hypertension and elevated plasma renin activity and aldosterone levels. Imaging studies revealed a mass in the left kidney, which was further confirmed as a renin-producing lesion via selective venous catheterization. During the evaluation, the patient had acute-onset chest pain that was diagnosed as variant angina after a provocation test. After partial nephrectomy, the plasma renin activity and plasma aldosterone levels decreased and blood pressure normalized. We report a case of reninoma with variant angina. PMID- 26877960 TI - Peanut-induced acute oxalate nephropathy with acute kidney injury. AB - Oxalate nephropathy is commonly caused by ethylene glycol, vitamin C, and foods like star fruit that contain a lot of oxalate. Peanuts also have high oxalate contents. However, case reports of peanut-induced oxalate nephropathy are not common. Here, we describe a case of peanut-induced acute oxalate nephropathy with acute kidney injury and intend to demonstrate the conditions under which peanut induced oxalate nephropathy is likely to occur. PMID- 26877962 TI - Prime determinants of serum phosphorus level in hemodialysis patients. PMID- 26877961 TI - A case of Fanconi syndrome accompanied by crystal depositions in tubular cells in a patient with multiple myeloma. AB - Fanconi syndrome (FS) is a rare condition that is characterized by defects in the proximal tubular function. A 48-year-old woman was admitted for evaluation of proteinuria. The patient showed normal anion gap acidosis, normoglycemic glycosuria, hypophosphatemia, and hypouricemia. Thus, her condition was compatible with FS. The M peak was found behind the beta globulin region in urine protein electrophoresis. Upon bone marrow examination, we found that 24% of cells were CD138+ plasma cells with kappa restriction. From a kidney biopsy, we found crystalline inclusions within proximal tubular epithelial cells. Thereafter, she was diagnosed with FS accompanied by multiple myeloma. The patient received chemotherapy and autologous stem cell transplantation, and obtained very good partial hematologic response. However, proximal tubular dysfunction was persistent until 1 year after autologous stem cell transplantation. In short, we report a case of FS accompanied by multiple myeloma, demonstrating crystalline inclusion in proximal tubular cells on kidney biopsy. PMID- 26877963 TI - Chronic exit-site care using povidone-iodine versus normal saline in peritoneal dialysis patients. PMID- 26877964 TI - Chronic renal failure induces cell death in rat hippocampal CA1 via upregulation of alphaCaMKII/NR2A synaptic complex and phosphorylated GluR1-containing AMPA receptor cascades. AB - BACKGROUND: N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5 methylisoxazole-4-propinoic acid (AMPA) receptors bound to postsynaptic density 95 (PSD-95) and alpha isoform of calcium/calmodulin-dependent protein kinase II (alphaCaMKII) is fundamentally involved in the regulation of working memory. The aim of present study was to investigate the alterations of NMDA and AMPA receptors responsible for hippocampal synaptic dysfunction and selective neuronal cell death after chronic renal failure (CRF) which may be associated with impairment of working memory. METHODS: Altered interactions between NMDA and AMPA receptors and PSD-95 and alphaCaMKII were analyzed in the cornu ammonis (CA) 1 and CA3/dentate gyrus (DG) subfields of the uremic rat hippocampi using the immunoblotting and immunoprecipitation methods. RESULTS: Uremia induced by CRF produced necrotic cell death and decreased neuronal nucleoli protein levels in the hippocampal CA1 subfield, but not in the CA3/DG subfields. The CA1 subfields of CRF rats exhibited significant decreases and increases, respectively, in the expressions of PSD-95/NR2B and alphaCaMKII/NR2A synaptic complex. Moreover, increased phosphorylation of glutamate receptor type 1 (GluR1) AMPA receptor at ser831 was observed in the CA1 subfield after CRF. CONCLUSION: These hippocampal CA1 neuronal vulnerability may be responsible for memory dysfunction after CRF as mediated by an increase in NR2A-containing NMDA receptors bound to alphaCaMKII and subsequent activation of GluR1-containing AMPA receptors caused by the phosphorylation of GluR1 at ser831. PMID- 26877965 TI - Emphysematous pyelonephritis initially presenting as a spontaneous subcapsular hematoma in a diabetic patient. AB - Emphysematous pyelonephritis (EPN) is a life-threatening infection characterized by the formation of gas. Complications of EPN include septic shock, acute renal failure, and disseminated intravascular coagulation. Spontaneous subcapsular hematoma (SCH) has also been reported as a rare complication of EPN, although there have been no reports to date of this occurring prior to the presentation of EPN. We report a case of EPN that initially presented as spontaneous SCH. The patient was admitted for left flank pain, and initial computed tomography revealed SCH without any air shadows. Laboratory findings and clinical symptoms suggested the presence of urinary tract infection and the patient was started on antibiotics. Fever developed 24 hours after admission. On follow-up computed tomography 7 days later, EPN was newly observed, and a percutaneous drain was inserted. Blood, urine, and drainage fluid cultures all revealed growth of extended-spectrum beta-lactamase-negative Escherichia coli. PMID- 26877966 TI - A new connecting technique in partial replantation of a ruptured peritoneal dialysis catheter. AB - Peritoneal dialysis catheter ruptures have been managed by immediate removal and subsequent reinsertion of the catheter which inevitably entails interruption in peritoneal dialysis and a need for vascular access. A 36-year-old man on continuous ambulatory peritoneal dialysis complaining of dialysate leakage was found to have a small rupture near the outer cuff of the peritoneal dialysis catheter. Rather than employing the traditional method of exchanging the whole catheter, a partial replantation procedure to salvage the still-functioning conduit was performed. Two peritoneal dialysis adaptors were used to connect the end of the remaining old catheter to a new extraperitoneal segment of a new catheter and a piece of a transfer set to connect the adaptors. A novel, yet simple and safe, means of partial peritoneal dialysis catheter replantation when managing catheter injuries is suggested. PMID- 26877967 TI - Remission of secondary membranous nephropathy in a patient with Kimura disease after surgical resection. AB - Kimura disease (KD) is an eosinophilic, granulomatous, benign, chronic inflammatory disease with an unknown etiology. A 33-year-old woman visited our hospital because of a palpable, left subclavian mass, a left scapulo-anterior pseudoaneurysm, and nephrotic syndrome. Her subclavian lymph node biopsy examination result was consistent with KD, and results of a renal biopsy indicated secondary membranous nephropathy. After renal histological examination confirmed nephropathy, treatment with prednisolone and cyclosporine was initiated, which was maintained for over 1 year. However, this therapy only provided a transient improvement in proteinuria. One year after commencing the treatment, both proteinuria and azotemia aggravated as the left axillary mass doubled in size. Finally, the mass was surgically excised, following which the azotemia rapidly normalized and proteinuria resolved within 1 month. This case shows that tumor resection in a patient with KD with secondary nephropathy may resolve secondary renal manifestations. Furthermore, reversible renal dysfunction may be caused by unknown secreted molecules. PMID- 26877968 TI - Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis. AB - Thromboembolism is a major complication of nephrotic syndrome. Renal vein thrombosis and deep vein thrombosis are relatively common, especially in membranous nephropathy. However, the incidence of portal vein and superior mesenteric vein (SMV) thrombosis in patients with nephrotic syndrome is very rare. To date, several cases of portal vein thrombosis treated by anticoagulation therapy, not by thrombolytic therapy, have been reported as a complication of nephrotic syndrome. Here, we report a case of portal, splenic, and SMV thrombosis in a patient with a relapsed steroid dependent minimal change disease who was treated successfully with anticoagulation and thrombolytic therapy using urokinase. Radiologic findings and his clinical conditions gradually improved. Six months later, a complete remission of the nephrotic syndrome was observed and the follow-up computed tomography scan showed the disappearance of all portal vein, splenic vein, and SMV thrombi. PMID- 26877970 TI - Performance comparison of estimated glomerular filtration rate equations. PMID- 26877969 TI - Improvement of Erdheim-Chester disease-related renal failure after treatment with anakinra. AB - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by infiltrates of lipid-laden CD68(+)/CD1a(-) histiocytes, affecting heart, lungs, central nervous system, and bones. Kidney and adjacent structures can also be affected, leading to renal failure in about 30% of cases. The diagnosis is challenging, and treatment is generally based on administration of interferon-alpha (IFNalpha), but preliminary results also showed the therapeutic efficacy of anakinra, an antagonist of the receptor of interleukin-1 (IL-1). We report the case of an elderly patient with ECD and severe involvement of the heart and kidneys who was successfully treated with anakinra. PMID- 26877971 TI - Job demands, burnout, and engagement among nurses: A multi-level analysis of ORCAB data investigating the moderating effect of teamwork. AB - According to the Job Demands-Resources (JD-R) model, burnout and engagement are psychological reactions that develop when individual characteristics interact with work characteristics. This study tests the JD-R model using multilevel analysis to test the main and moderating effects of teamwork effectiveness among 1156 nurses in 93 departments from seven European countries. Workload, emotional and organizational demands were positively associated with emotional exhaustion, depersonalization, and negatively with vigor. Emotional and organizational demands were negatively associated with dedication. Teamwork effectiveness was positively associated with engagement. We found no evidence for the moderating effect of teamwork effectiveness in reducing individual perceptions of demands. PMID- 26877972 TI - The Role of History in Debates Regarding the Boundaries of Medical Confidentiality and Privacy. AB - Medical confidentiality and privacy are often given a long pedigree as core issues in medical ethics that can be traced back to the Hippocratic Oath. However, it is only recently that focused historical work has begun to examine and analyse in greater detail how the boundaries of medical confidentiality and privacy have evolved within a variety of cultural contexts during the modern period. Such research illustrates the ways in which this process has been shaped by a range of issues, individuals, interest groups and events; and been influenced as much by pragmatic concerns as by theoretical arguments. This paper presents a case for the merits of promoting further historical work on these topics. It suggests that greater support for, and recognition of, historical research has a number of potential benefits. These include providing meaningful context to current interdisciplinary discussions of the collection and use of patient information; improving knowledge and understanding of the foundations on which current policy and practice are built; and promoting public engagement and understanding of the evolution of medical confidentiality and privacy as complex public interest issues. PMID- 26877973 TI - Quantitation of 4,4'-methylene diphenyl diisocyanate human serum albumin adducts. AB - 4,4'-Methylene diphenyl diisocyanate (herein 4,4'-MDI) is used in the production of polyurethane foams, elastomers, coatings, adhesives and the like for a wide range of commercial products. Occupational exposure to MDI levels above current airborne exposure limits can elicit immune mediated hypersensitivity reactions such as occupational asthma in sensitive individuals. To accurately determine exposure, there has been increasing interest in developing analytical methods to measure internal biomarkers of exposure to MDI. Previous investigators have reported methodologies for measuring MDI diamine metabolites and MDI-Lysine (4,4' MDI-Lys) adducts. The purpose of this study was to develop and validate an ultra performance liquid chromatography isotope dilution tandem mass spectrometry (UPLC ID/MS/MS) quantitation method via a signature peptide approach to enable biomonitoring of 4,4'-MDI adducted to human serum albumin (HSA) in plasma. A murine, anti-4,4'-MDI monoclonal IgM antibody was bound to magnetic beads and utilized for enrichment of the MDI adducted HSA. Following enrichment, trypsin digestion was performed to generate the expected 414 site (primary site of adduction) 4,4'-MDI-adducted HSA signature peptide that was quantified by UPLC ID/MS/MS. An Agilent 6530 UPLC/quadrupole time of flight MS (QTOF) system was utilized for intact adducted protein analysis and an Agilent 6490 UPLC/MS/MS system operated in multiple reaction monitoring (MRM) mode was utilized for quantification of the adducted signature peptide biomarker both for in chemico and worker serum samples. Worker serum samples were initially screened utilizing the previously developed 4,4'-MDI-Lys amino acid method and results showed that 12 samples were identified as quantifiable for 4,4'-MDI-Lys adducts. The signature peptide adduct approach was applied to the 12 worker samples identified as quantifiable for 4,4'-MDI-Lys adducts. Results indicated no positive results were obtained above the quantification limit by the signature peptide approach. If the 414 site of lysine adduction accounted for 100% of the 4,4'-MDI adductions in the signature peptide adduct approach, the three highest quantifiable samples by the 4,4'-MDI-Lys method should have at least been detectable by the signature peptide method. Results show that although the 4,4'-MDI signature peptide approach is more selective, it is 18 times less sensitive than the 4,4'-MDI-Lys method, thus limiting the ability to detect adduct levels relative to the 4,4' MDI-Lys amino acid method. PMID- 26877974 TI - Physician perceptions of HIV cure in China: A mixed methods review and implications for HIV cure research. AB - There are over 100 clinical trials worldwide focused on developing an HIV cure. Research participants will assume substantial individual risks while receiving little or no individual benefit. Physicians will have important dual roles of leading HIV cure research studies and guiding patient expectations. Many low and middle-income nations have started HIV cure trials, including China. The goal of this study was to better understand physician attitudes, behaviors, and perceptions of HIV cure research within the context of China. We conducted a quantitative and qualitative evidence review of published literature on physician perceptions of HIV cure in China. Quantitative survey data revealed that physicians rarely believed HIV was curable, but this perception may be more common compared to other countries. Qualitative data showed that inconsistent terminology used among physicians may contribute to the perception of HIV as curable. The belief that HIV is curable among some physicians in China may be related to the influence of traditional Chinese medicine beliefs. Rather than seeking elimination of pathogens, traditional Chinese medicine aims to achieve harmony between organs and a vital life force. In this context, HIV infection can be seen as a temporary state of imbalance rather than an irreversible change. There is a wide range of physician perceptions about HIV cure in China. Conflicting information about HIV cure from physicians and other sources could thwart the progress of HIV cure research. Enhancing patient-physician communication about ongoing HIV cure research trials will be important for developing an HIV cure. PMID- 26877976 TI - Reader's Forum. PMID- 26877975 TI - Nurse leaders' Attitudes, Self-Efficacy and training Needs for Implementing Evidence-Based Practice: Is It Time for a Change toward Safe Care? AB - INTRODUCTION: Evidence-based practice (EBP) has been recognized as the gold standard for safe and high quality care. Nurse leaders have a strategic position in terms of initiating changes in clinical settings for successfully implementing EBP. Therefore, the factors that influence implementing EBP must be measured. AIMS: To examine nurse leaders' attitudes, self-efficacy, and training needs for implementing evidence-based practice. PLACE AND DURATION OF STUDY: Four teaching hospitals affiliated to Kerman University of Medical Sciences in the southeast of Iran from January to April 2014. METHODS: A cross-sectional study was conducted on 70 nurse leaders from four teaching hospitals. After using a modified forward/backward translation procedure to create a Persian version of "perceptions of nurses of evidence-based practice questionnaire", data were collected from the participants and analyzed using SPSS (version 20), descriptive statistics, Student's t-test, analysis of variance (ANOVA), and Pearson's correlation. RESULTS: Most (82.86%) of the participants had not attended any specific training course on the implementation of EBP and 80% had not been involved in any research activities. Nurse leaders' attitudes toward EBP were unfavorable (mean=2.55+/-0.88), their levels of self-efficacy in EBP skills were weak (mean=2.64+/-1.31), and their demand for training in all of the EBP areas was moderate (3.89+/-.97). CONCLUSION: Current practice of nurse leaders is not evidence-based, which is worrisome and can result in serious deficiencies in the quality and safety of nursing care. Nurse leaders must attempt to equip themselves with the attitudes and skills required to change in practice using EBP. PMID- 26877977 TI - A comparison of the precision of three-dimensional images acquired by 2 digital intraoral scanners: effects of tooth irregularity and scanning direction. AB - OBJECTIVE: The purpose of this study was to compare the precision of three dimensional (3D) images acquired using iTero(r) (Align Technology Inc., San Jose, CA, USA) and Trios(r) (3Shape Dental Systems, Copenhagen, Denmark) digital intraoral scanners, and to evaluate the effects of the severity of tooth irregularities and scanning sequence on precision. METHODS: Dental arch models were fabricated with differing degrees of tooth irregularity and divided into 2 groups based on scanning sequence. To assess their precision, images were superimposed and an optimized superimposition algorithm was employed to measure any 3D deviation. The t-test, paired t-test, and one-way ANOVA were performed (p < 0.05) for statistical analysis. RESULTS: The iTero(r) and Trios(r) systems showed no statistically significant difference in precision among models with differing degrees of tooth irregularity. However, there were statistically significant differences in the precision of the 2 scanners when the starting points of scanning were different. The iTero(r) scanner (mean deviation, 29.84 +/ 12.08 um) proved to be less precise than the Trios(r) scanner (22.17 +/- 4.47 um). CONCLUSIONS: The precision of 3D images differed according to the degree of tooth irregularity, scanning sequence, and scanner type. However, from a clinical standpoint, both scanners were highly accurate regardless of the degree of tooth irregularity. PMID- 26877978 TI - Accuracy of Bolton analysis measured in laser scanned digital models compared with plaster models (gold standard) and cone-beam computer tomography images. AB - OBJECTIVE: The aim of this study was to compare the accuracy of Bolton analysis obtained from digital models scanned with the Ortho Insight three-dimensional (3D) laser scanner system to those obtained from cone-beam computed tomography (CBCT) images and traditional plaster models. METHODS: CBCT scans and plaster models were obtained from 50 patients. Plaster models were scanned using the Ortho Insight 3D laser scanner; Bolton ratios were calculated with its software. CBCT scans were imported and analyzed using AVIZO software. Plaster models were measured with a digital caliper. Data were analyzed with descriptive statistics and the intraclass correlation coefficient (ICC). RESULTS: Anterior and overall Bolton ratios obtained by the three different modalities exhibited excellent agreement (> 0.970). The mean differences between the scanned digital models and physical models and between the CBCT images and scanned digital models for overall Bolton ratios were 0.41 +/- 0.305% and 0.45 +/- 0.456%, respectively; for anterior Bolton ratios, 0.59 +/- 0.520% and 1.01 +/- 0.780%, respectively. ICC results showed that intraexaminer error reliability was generally excellent (> 0.858 for all three diagnostic modalities), with < 1.45% discrepancy in the Bolton analysis. CONCLUSIONS: Laser scanned digital models are highly accurate compared to physical models and CBCT scans for assessing the spatial relationships of dental arches for orthodontic diagnosis. PMID- 26877979 TI - Patients' and parents' concerns and decisions about orthodontic treatment. AB - OBJECTIVE: Patients' and parents' expectations are important in orthodontic treatment decision making. The literature generally demonstrates the perceived benefits of orthodontic treatment, but patients' and their parents' concerns about orthodontic treatment have not been investigated comprehensively. The aim of this study was to identify patients' and parents' concerns about orthodontic treatment and compare them according to sex, age, and treatment demand level. METHODS: One hundred and eighty-nine children and their parents were interviewed about concerns related to orthodontic treatment. Patients and parents were asked about orthodontic treatment decisions. Answers were recorded as "yes," "no," or "don't know." Chi-squared and Fisher's exact tests were used to compare concerns between age groups, sexes, and treatment demand levels. Kappa statistics were used to assess agreement between patients and their parents. RESULTS: Concerns about orthodontic treatment were gathered under 10 items as follows: "feeling pain," "the appearance of braces," "being teased," "avoiding smiling," "speech problems," "dietary changes," "problems with transportation," "economic problems," "long treatment duration," and "missing school." There was no statistically significant difference in concerns between the sexes or age groups. Some concern items and treatment demand were inversely related in patients. CONCLUSIONS: The results of this study demonstrate patients' and parents' concerns about orthodontic treatment. Differences between the concerns of patients with different treatment demands imply that children might reject orthodontic treatment because of their concerns. Appropriate consultation of patients addressing their concerns may help reduce anxiety and improve the acceptance of treatment. PMID- 26877980 TI - Computerized occlusal analysis: correlation with occlusal indexes to assess the outcome of orthodontic treatment or the severity of malocculusion. AB - OBJECTIVE: The aims of our study were to verify the validity of the T-Scan III system (Tekscan) as an objective occlusal evaluation tool, and to assess the differences between two occlusal indexes-the peer assessment rating (PAR) index and the American Board of Orthodontics objective grading system (OGS)-by comparing the scores derived from the T-Scan III system with the two occlusal indexes and analyzing the correlations between them. METHODS: The final study sample included 48 adult volunteers (39 men and 9 women, mean age 24.14 +/- 3.16 years), after excluding 29 volunteers whose occlusion could not be evaluated by the T-Scan III system due to severe skeletal or occlusal problems. PAR index and OGS scores were assessed using dental study models, and measurements of centric occlusion, protrusive movement, and lateral excursion movement were obtained via the T-Scan III system. The results were analyzed to determine correlations. RESULTS: Occlusal analysis by the T-Scan III system was clinically reliable (p < 0.05), and the PAR index and OGS scores were significantly correlated with several measurements obtained with the T-Scan III system (p < 0.05). CONCLUSIONS: The T-Scan III system is a quantitative and reliable method for occlusal evaluation, and represents a potential substitute for occlusal indexes. Compared to the PAR index, the OGS scores of more variables were significantly correlated with the T-Scan measurements. PMID- 26877981 TI - A survey on retention practice among orthodontists in Malaysia. AB - OBJECTIVE: The aim of this study was to evaluate retention practices commonly employed by orthodontists. The objectives were to identify the types of retainer frequently used and to investigate the variations in retention practice. METHODS: A total of 97 orthodontists were randomly selected, and a questionnaire consisting of 25 multiple-choice questions sent to them by mail. Upon receiving of the completed questionnaires, the data were statistically analyzed. RESULTS: A total of 32 responses were received; among these, 59.4% of orthodontists' practiced is in a government setting and 40.6% were in private practice. A vacuum formed retainer was the most commonly used removable retainer for both maxillary (46.9%) and mandibular (46.9%) arches, followed by a Hawley retainer (maxilla, 43.8%; mandible, 37.5%), and a fixed retainer (maxilla, 3.1%; mandible, 9.4%). Of the responding orthodontists, 78.1% prescribed full-time wear (more than 20 h per day) for a duration of 3-9 months for a maxillary arch, compared to 71.9% for the mandibular arch. Only 18.8% of the orthodontists prescribed part-time wear of the retainer for the maxillary arch, compared to 21.9% for the mandibular arch. The majority of orthodontists did not instruct their patients to stop wearing removable retainers (71.9%) or fixed retainers (66.8%) at any specific time and they preferred their patients to continue wearing retainers. CONCLUSIONS: Vacuum formed retainers are the most commonly used retainers among orthodontists. The majority of orthodontists prescribed full-time wear for more than 20 h per day with a duration of 3-9 months and preferred indefinite use of the retainer. PMID- 26877982 TI - Facial and occlusal esthetic improvements of an adult skeletal Class III malocclusion using surgical, orthodontic, and implant treatment. AB - The aim of this clinical report is to describe the complex treatment of an adult Class III malocclusion patient who was disappointed with the outcome of a previous oral rehabilitation. Interdisciplinary treatment planning was performed with a primary indication for implant removal because of marginal bone loss and gingival recession, followed by orthodontic and surgical procedures to correct the esthetics and skeletal malocclusion. The comprehensive treatment approach included: (1) implant removal in the area of the central incisors; (2) combined orthodontic decompensation with mesial displacement and forced extrusion of the lateral incisors; (3) extraction of the lateral incisors and placement of new implants corresponding to the central incisors, which received provisional crowns; (4) orthognathic surgery for maxillary advancement to improve occlusal and facial relationships; and finally, (5) orthodontic refinement followed by definitive prosthetic rehabilitation of the maxillary central incisors and reshaping of the adjacent teeth. At the three-year follow-up, clinical and radiographic examinations showed successful replacement of the central incisors and improved skeletal and esthetic appearances. Moreover, a Class II molar relationship was obtained with an ideal overbite, overjet, and intercuspation. In conclusion, we report the successful esthetic anterior rehabilitation of a complex case in which interdisciplinary treatment planning improved facial harmony, provided gingival architecture with sufficient width and thickness, and improved smile esthetics, resulting in enhanced patient comfort and satisfaction. This clinical case report might be useful to improve facial esthetics and occlusion in patients with dentoalveolar and skeletal defects. PMID- 26877983 TI - Analysis of midpalatal miniscrew-assisted maxillary molar distalization patterns with simultaneous use of fixed appliances: A preliminary study. AB - Skeletal anchorage-assisted upper molar distalization has become one of the standard treatment modalities for the correction of Class II malocclusion. The purpose of this study was to analyze maxillary molar movement patterns according to appliance design, with the simultaneous use of buccal fixed orthodontic appliances. The authors devised two distinct types of midpalatal miniscrew assisted maxillary molar distalizers, a lingual arch type and a pendulum type. Fourteen patients treated with one of the two types of distalizers were enrolled in the study, and the patterns of tooth movement associated with each type were compared. Pre- and post-treatment lateral cephalograms were analyzed. The lingual arch type was associated with relatively bodily upper molar distalization, while the pendulum type was associated with distal tipping with intrusion of the upper molar. Clinicians should be aware of the expected tooth movement associated with each appliance design. Further well designed studies with larger sample sizes are required. PMID- 26877984 TI - Comparison of canal transportation in simulated curved canals prepared with ProTaper Universal and ProTaper Gold systems. AB - OBJECTIVES: The purpose of this study was to assess the ability of ProTaper Gold (PTG, Dentsply Maillefer) in maintaining the original profile of root canal anatomy. For that, ProTaper Universal (PTU, Dentsply Maillefer) was used as reference techniques for comparison. MATERIALS AND METHODS: Twenty simulated curved canals manufactured in clear resin blocks were randomly assigned to 2 groups (n = 10) according to the system used for canal instrumentation: PTU and PTG groups, upto F2 files (25/0.08). Color stereomicroscopic images from each block were taken exactly at the same position before and after instrumentation. All image processing and data analysis were performed with an open source program (FIJI). Evaluation of canal transportation was obtained for two independent canal regions: straight and curved levels. Student's t test was used with a cut-off for significance set at alpha = 5%. RESULTS: Instrumentation systems significantly influenced canal transportation (p < 0.0001). A significant interaction between instrumentation system and root canal level (p < 0.0001) was found. PTU and PTG systems produced similar canal transportation at the straight part, while PTG system resulted in lower canal transportation than PTU system at the curved part. Canal transportation was higher at the curved canal portion (p < 0.0001). CONCLUSIONS: PTG system produced overall less canal transportation in the curved portion when compared to PTU system. PMID- 26877985 TI - An in vitro evaluation of the accuracy of four electronic apex locators using stainless-steel and nickel-titanium hand files. AB - OBJECTIVES: The purpose of this in vitro study was to evaluate the accuracy of working length (WL) determination of four electronic apex locators (EALs), namely, Root ZX (RZX), Elements diagnostic unit and apex locator (ELE), SybronEndo Mini Apex locator (MINI) and Propex pixi (PIXI) using Stainless steel (SS) and nickel-titanium (NiTi) hand files. The null hypothesis was that there was no difference between canal length determination by SS and NiTi files of 4 EALs. MATERIALS AND METHODS: Sixty extracted, single rooted human teeth were decoronated and the canal orifice flared. The actual length (AL) was assessed visually, and the teeth were embedded in an alginate model. The electronic length (EL) measurements were recorded with all four EALs using SS and NiTi files at '0.5' reading on display. The differences between the AL and EL were compared. RESULTS: The results obtained with each EAL with SS and NiTi files were compared with AL. A paired sample t test showed that there was a statistical significant difference between EAL readings with SS and NiTi files for RZX and MINI (p < 0.05). The accuracy of RZX, ELE, MINI and PIXI within +/- 0.5 mm of AL with SS/NiTi files were 93.3%/70%, 90%/91.7%, 95%/68.3%, and 83.3%/83.3%, respectively. CONCLUSIONS: The results of this study indicate that Root ZX was statistically more accurate with NiTi files compared to SS files, while MINI was statistically more accurate with SS files compared to NiTi files. ELE and PIXI were not affected by the alloy type of the file used to determine WL. PMID- 26877986 TI - Effect of acidic solutions on the microhardness of dentin and set OrthoMTA and their cytotoxicity on murine macrophage. AB - OBJECTIVES: To evaluate the effects of three acids on the microhardness of set mineral trioxide aggregate (MTA) and root dentin, and cytotoxicity on murine macrophage. MATERIALS AND METHODS: OrthoMTA (BioMTA) was mixed and packed into the human root dentin blocks of 1.5 mm diameter and 5 mm height. Four groups, each of ten roots, were exposed to 10% citric acid (CA), 5% glycolic acid (GA), 17% ethylenediaminetetraacetic acid (EDTA), and saline for five minutes after setting of the OrthoMTA. Vickers surface microhardness of set MTA and dentin was measured before and after exposure to solutions, and compared between groups using one-way ANOVA with Tukey test. The microhardness value of each group was analyzed using student t test. Acid-treated OrthoMTA and dentin was examined by scanning electron microscope (SEM). Cell viability of tested solutions was assessed using WST-8 assay and murine macrophage. RESULTS: Three test solutions reduced microhardness of dentin. 17% EDTA demonstrated severe dentinal erosion, significantly reduced the dentinal microhardness compared to 10% CA (p = 0.034) or 5% GA (p = 0.006). 10% CA or 5% GA significantly reduced the surface microhardness of set MTA compared to 17% EDTA and saline (p < 0.001). Acid treated OrthoMTA demonstrated microporous structure with destruction of globular crystal. EDTA exhibited significantly more cellular toxicity than the other acidic solutions at diluted concentrations (0.2, 0.5, 1.0%). CONCLUSIONS: Tested acidic solutions reduced microhardness of root dentin. Five minute's application of 10% CA and 5% GA significantly reduced the microhardness of set OrthoMTA with lower cellular cytotoxicity compared to 17% EDTA. PMID- 26877987 TI - Quality of root canal fillings using three gutta-percha obturation techniques. AB - OBJECTIVES: The goal of this study was to compare the density of gutta-percha root fillings obturated with the following techniques: cold lateral (CL) compaction, ultrasonic lateral (UL) compaction, and warm vertical (WV) compaction. MATERIALS AND METHODS: Thirty-three extracted mandibular first molars, with two separate mesial canals in each, were selected. After instrumentation, the canals were stratified into three groups based on canal length and curvature, and underwent obturation with one of the techniques. No sealer was used in order to avoid masking any voids. The teeth were imaged pre- and post-obturation using micro-computed tomography. The reconstructed three dimensional images were analyzed volumetrically to determine the amount of gutta percha present in every 2 mm segment of the canal. P values < 0.05 were considered to indicate statistical significance. RESULTS: The overall mean volume fraction of gutta-percha was 68.51 +/- 6.75% for CL, 86.56 +/- 5.00% for UL, and 88.91 +/- 5.16% for WV. Significant differences were found between CL and UL and between CL and WV (p < 0.05), but not between UL and WV (p = 0.526). The gutta percha density of the roots treated with WV and UL increased towards the coronal aspect, but this trend was not noted in the CL group. CONCLUSIONS: WV compaction and UL compaction produced a significantly denser gutta-percha root filling than CL compaction. The density of gutta-percha was observed to increase towards the coronal aspect when the former two techniques were used. PMID- 26877988 TI - Evaluation of reparative dentin formation of ProRoot MTA, Biodentine and BioAggregate using micro-CT and immunohistochemistry. AB - OBJECTIVES: The purpose of this study was to assess the ability of two new calcium silicate-based pulp-capping materials (Biodentine and BioAggregate) to induce healing in a rat pulp injury model and to compare them with mineral trioxide aggregate (MTA). MATERIALS AND METHODS: Eighteen rats were anesthetized, cavities were prepared and the pulp was capped with either of ProRoot MTA, Biodentine, or BioAggregate. The specimens were scanned using a high-resolution micro-computed tomography (micro-CT) system and were prepared and evaluated histologically and immunohistochemically using dentin sialoprotein (DSP). RESULTS: On micro-CT analysis, the ProRoot MTA and Biodentine groups showed significantly thicker hard tissue formation (p < 0.05). On H&E staining, ProRoot MTA showed complete dentin bridge formation with normal pulpal histology. In the Biodentine and BioAggregate groups, a thick, homogeneous hard tissue barrier was observed. The ProRoot MTA specimens showed strong immunopositive reaction for DSP. CONCLUSIONS: Our results suggest that calcium silicate-based pulp-capping materials induce favorable effects on reparative processes during vital pulp therapy and that both Biodentine and BioAggregate could be considered as alternatives to ProRoot MTA. PMID- 26877989 TI - Marginal and internal fit of nano-composite CAD/CAM restorations. AB - OBJECTIVES: The purpose of this study was to compare the marginal and internal fit of nano-composite CAD-CAM restorations. MATERIALS AND METHODS: A full veneer crown and an mesio-occluso-distal (MOD) inlay cavity, which were prepared on extracted human molars, were used as templates of epoxy resin replicas. The prepared teeth were scanned and CAD-CAM restorations were milled using Lava Ultimate (LU) and experimental nano-composite CAD/CAM blocks (EB) under the same milling parameters. To assess the marginal and internal fit, the restorations were cemented to replicas and were embedded in an acrylic mold for sectioning at 0.5 mm intervals. The measured gap data were pooled according to the block types and measuring points for statistical analysis. RESULTS: Both the block type and measuring point significantly affected gap values, and their interaction was significant (p = 0.000). In crowns and inlays made from the two blocks, gap values were significantly larger in the occlusal area than in the axial area, while gap values in the marginal area were smallest (p < 0.001). Among the blocks, the restorations milled from EB had a significantly larger gap at all measuring points than those milled from LU (p = 0.000). CONCLUSIONS: The marginal and internal gaps of the two nano-composite CAD/CAM blocks differed according to the measuring points. Among the internal area of the two nano-composite CAD/CAM restorations, occlusal gap data were significantly larger than axial gap data. The EB crowns and inlays had significantly larger gaps than LU restorations. PMID- 26877990 TI - Antioxidant therapy enhances pulpal healing in bleached teeth. AB - OBJECTIVES: The purpose of this study was to evaluate the histopathological effects of an antioxidant therapy on the pulp tissue of rat teeth exposed to a bleaching gel with 35% hydrogen peroxide. MATERIALS AND METHODS: Forty rats were subjected to oral ingestion by gavage of distilled water (DW) or ascorbic acid (AA) 90 min before the bleaching therapy. For the bleaching treatment, the agent was applied twice for 5 min each to buccal surfaces of the first right mandibular molars. Then, the animals were sacrificed at 6 hr, 24 hr, 3 day, or 7 day post bleaching, and the teeth were processed for microscopic evaluation of the pulp tissue. RESULTS: At 6 hr, the pulp tissue showed moderate inflammatory reactions in all teeth of both groups. In the DW and AA groups, 100% and 80% of teeth exhibited pulp tissue with significant necrosis and intense tissue disorganization, respectively. At 24 hr, the AA-treated group demonstrated a greater regenerative capability than the DW group, with less intense inflammatory reaction and new odontoblast layer formation in 60% of the teeth. For up to the 7 day period, the areas of pulpal necrosis were replaced by viable connective tissue, and the dentin was underlined by differentiated odontoblast-like cells in most teeth of both groups. CONCLUSIONS: A slight reduction in initial pulpal damage during post-bleaching was promoted by AA therapy. However, the pulp tissue of AA-treated animals featured faster regenerative potential over time. PMID- 26877991 TI - Analysis of C-shaped root canal configuration in maxillary molars in a Korean population using cone-beam computed tomography. AB - OBJECTIVES: The purpose of this study was to investigate the incidence of root fusion and C-shaped root canals in maxillary molars, and to classify the types of C-shaped canal by analyzing cone-beam computed tomography (CBCT) in a Korean population. MATERIALS AND METHODS: Digitized CBCT images from 911 subjects were obtained in Chosun University Dental Hospital between February 2010 and July 2012 for orthodontic treatment. Among them, a total of selected 3,553 data of maxillary molars were analyzed retrospectively. Tomography sections in the axial, coronal, and sagittal planes were displayed by PiViewstar and Rapidia MPR software (Infinitt Co.). The incidence and types of root fusion and C-shaped root canals were evaluated and the incidence between the first and the second molar was compared using Chi-square test. RESULTS: Root fusion was present in 3.2% of the first molars and 19.5% of the second molars, and fusion of mesiobuccal and palatal root was dominant. C-shaped root canals were present in 0.8% of the first molars and 2.7% of the second molars. The frequency of root fusion and C-shaped canal was significantly higher in the second molar than the first molar (p < 0.001). CONCLUSIONS: In a Korean population, maxillary molars showed total 11.3% of root fusion and 1.8% of C-shaped root canals. Furthermore, root fusion and C shaped root canals were seen more frequently in the maxillary second molars. PMID- 26877992 TI - Accidental injury of the inferior alveolar nerve due to the extrusion of calcium hydroxide in endodontic treatment: a case report. AB - During clinical endodontic treatment, we often find radiopaque filling material beyond the root apex. Accidental extrusion of calcium hydroxide could cause the injury of inferior alveolar nerve, such as paresthesia or continuous inflammatory response. This case report presents the extrusion of calcium hydroxide and treatment procedures including surgical intervention. A 48 yr old female patient experienced Calcipex II extrusion in to the inferior alveolar canal on left mandibular area during endodontic treatment. After completion of endodontic treatment on left mandibular first molar, surgical intervention was planned under general anesthesia. After cortical bone osteotomy and debridement, neuroma resection and neurorrhaphy was performed, and prognosis was observed. But no improvement in sensory nerve was seen following surgical intervention after 20 mon. A clinician should be aware of extrusion of intracanal medicaments and the possibility of damage on inferior alveolar canal. Injectable type of calcium hydroxide should be applied with care for preventing nerve injury. The alternative delivery method such as lentulo spiral was suggested on the posterior mandibular molar. PMID- 26877993 TI - Endodontic treatment of a C-shaped mandibular second premolar with four root canals and three apical foramina: a case report. AB - This case report describes a unique C-shaped mandibular second premolar with four canals and three apical foramina and its endodontic management with the aid of cone-beam computer tomography (CBCT). C-shaped root canal morphology with four canals was identified under a dental operating microscope. A CBCT scan was taken to evaluate the aberrant root canal anatomy and devise a better instrumentation strategy based on the anatomy. All canals were instrumented to have a 0.05 taper using 1.0 mm step-back filing with appropriate apical sizes determined from the CBCT scan images and filled using a warm vertical compaction technique. A C shaped mandibular second premolar with multiple canals is an anatomically rare case for clinicians, yet its endodontic treatment may require a careful instrumentation strategy due to the difficulty in disinfecting the canals in the thin root area without compromising the root structure. PMID- 26877994 TI - Statistical notes for clinical researchers: Sample size calculation 1. comparison of two independent sample means. PMID- 26877995 TI - Predictable management of the cracked tooth. PMID- 26877996 TI - Questioning the spot light on Hi-tech endodontics. PMID- 26877997 TI - Trends in publication on evidence-based antioxidative herbal medicines in management of diabetic nephropathy. AB - BACKGROUND: Recently, popularity and use of herbal medicine in treatment of diabetes have been increased. Since, oxidative stress is known as the main underlying pathophysiology of diabetes and its complications, the purpose of this bibliometric study is to assess the global scientific production analysis and developing its trend in field of antioxidative hypoglycemic herbal medicines and diabetic nephropathy focusing on the scientific publication numbers, citations, geographical distribution in the world and determining the main journal (source) in the field. METHODS: Our search terms were "diabetes", "renal", "nephropathy", "herb", "Chinese medicine", "traditional medicine", and "antioxidant" from Scopus database until January 2015 and analysis of the distribution of words in the publication year, main journal (source) in the field, geographical distribution, documents' type and language, subject area, and h-index of citations were crried out. The Scopus analysis tools and VOSviewer software version 1.6.3 have been used for analysis. RESULTS: Within 1166 papers were published until year 2015, 78 studies were related to this topic in human. Increasing trend in number of related researches was shown. Fifty eight percent of the published papers were original articles, and the highest number was produced in 2013 with 21 documents. Top subject areas were medicine with global publication share of 71.8 %, and pharmacology was ranked the second (39.7 %). Iran was the first country with global publication. The total citation of the documents were 2518 times and h index was 24. The highest cited paper was a review article with 336 citation number, and top source was "Journal of Medicinal Plants". Both of top authors and affiliation were from Iran; "Tehran University of Medical Sciences". Also, top author in the co-authorship mapping and clustering assessment was from Iran. CONCLUSIONS: Although, we found an ascending trend of scientific publications in field of antioxidative herbal medicine and diabetic nephropathy with a good position for Iran, the number of publications is insufficient and more researches in this topic is necessary. PMID- 26877998 TI - Does Malleolus non-Lifting Tympanoplasty have any Advantage Over Malleus Lifting Techniques? AB - INTRODUCTION: In order to achieve a higher success rate for tympanoplasty, different techniques have been developed, and a wide variety of grafting materials have been developed. One of the techniques currently receiving considerable attention involves not lifting the remaining of eardrum from the malleus and embedding the graft underneath in order to repair the eardrum correctly in its original position, as well as minimizing graft lateralization leading to progression of hearing rehabilitation. We compared the effects of tympanoplasty with and without malleus lifting on hearing loss in patients with chronic otitis media. MATERIALS AND METHODS: In this study, 30 consecutive patients diagnosed as having chronic otitis media without cholesteatoma were randomly assigned to two tympanoplasty groups; with or without malleus lifting. Air and bone conduction thresholds were recorded before and 45 days after the intervention. RESULTS: In groups, except for 8000 Hz, the air conduction was significantly improved following surgery. According to air conduction there was no difference between the groups before surgery at different frequencies, although it was improved to a greater degree in the group without lifting at 250 Hz postoperatively. The average post-operative air-bone gap (ABG) gain was significantly higher in all study frequencies in the target group. One of the effects of this technique is inner-ear protection from physical trauma to the ossicular chain, and prevention of damage to bone conduction. CONCLUSION: A higher hearing threshold and also higher ABG gain can be achieved by not lifting the remaining eardrum from the malleus and embedding the graft undereath it, especially at lower frequencies. PMID- 26877999 TI - Effect of Early Intervention on Language Development in Hearing-Impaired Children. AB - INTRODUCTION: Hearing loss from birth up to the age of 3 years has a negative effect on speech/language development and results in sensory, cognitive, emotional, and academic defects in adulthood by causing delayed development of communicative-linguistic abilities. The present study was performed in order to assess the effect of early intervention on language development in Persian children aged 6-7 years with severe sensorineural hearing loss. MATERIALS AND METHODS: Thirty boys and girls aged 6-7 years participated in this study, all of them had severe congenital sensorineural hearing loss in both ears. All children were using bilateral behind-the-ear hearing aid, and had similar economic/socio cultural backgrounds. Subjects were categorized into two groups based on the age of identification/intervention of hearing loss (3-6 and 12-15 months of age). The Persian TOLD-P3 test was used to evaluate language development in all subjects. Data collection was accomplished by observation, completion of questionnaires, and speech recording. RESULTS: There was a significant difference in language development in 11 sub-tests and five lingual gains on the Persian TOLD-P3 test between early (3-6 months of age) and late identified/intervened (12-15 months of age) hearing-impaired children (P[Formula: see text]0.05). Early identified/intervened hearing-impaired children had a notable preference in all assessed sub-tests and lingual gains. CONCLUSION: Early identification/intervention of hearing loss before the age of 6 months has a significant positive effect on a child's language development in terms of picture/relational/oral vocabulary, grammatical comprehension, sentence combining, grammatical completion, phonologic analysis, word differentiation, word production, semantics, and syntax. Moreover, early identification/ intervention of hearing loss develops the hearing-impaired child's lingual gains in visual vocabulary, grammatical completion, word differentiation, phonologic analysis, and word production. PMID- 26878000 TI - Effects of Hyperbilirubinemia on Auditory Brainstem Response of Neonates Treated with Phototherapy. AB - INTRODUCTION: One of the most common pathologies in neonates is hyperbilirubinemia, which is a good marker for damage to the central nervous system. The sensitivity of the auditory system to bilirubin has been previously documented, with much discrepancy in its effects on Auditory Brainstem Response results. Thus the objective of this study was to evaluate the effects of hyperbilirubinemia on Auditory Brainstem Response of neonates treated with phototherapy. MATERIALS AND METHODS: Forty-two term neonates with hyperbilirubinemia, who underwent phototherapy participated in this cross sectional study. The recording of Auditory Brainstem Response was made shortly after confirming that the total serum bilirubin level was greater than 15 ug/dl. Latency of waves I, III, V and inter-peak latencies of the waves were measured. To test the hypothesis about the difference of means between the two groups, continuous variables were compared using either the t-test (normal distribution) or the Mann-Whitney test (non-normal distribution). RESULTS: There was a significant increase in the absolute latencies of waves III and V, and I-III and I-V inter-peak latencies of the sample group compared to the control group in both ears (P<0.05). However, wave I absolute latency and III-V inter-peak interval did not show a significant difference between the two study groups (P>0.05). CONCLUSION: The results of this study underline the importance of the Auditory Brainstem Response Test as an efficient tool for monitoring the auditory brainstem pathway in neonates who are at risk of neurotoxicity and for diagnosing the earliest stages of auditory damage caused by high levels of bilirubin. PMID- 26878002 TI - Endoscopic Repair of CSF Rhinorrhea: An Institutional Experience. AB - INTRODUCTION: Endoscopic repair is considered the treatment of choice in cerebrospinal fluid (CSF) rhinorrhea. The aim of our study was to analyze the etiopathogenesis of CSF rhinorrhea, the outcome of treatment and the causes of failure in a developing-country setting. MATERIALS AND METHODS: A retrospective review of patients treated with endoscopic repair for CSF rhinorrhea at a tertiary care hospital in southern India from January 2002 to December 2009 identified 36 patients, the majority of them being women. The defects were closed in three layers using fat, fascia lata and nasal mucosa along with a fibrin sealant in the majority of the patients. Per-operatively, a subarachnoid drain was placed in all patients. Patients were followed up for 1 year. RESULTS: Spontaneous onset of CSF rhinorrhea was noted in 61% of patients. The most common site of leak was found to be the left cribriform plate area. Hence the most common cause of CSF rhinorrhea in our study was spontaneous and the second most common was post-traumatic. Our success rate on the first attempt at endoscopic repair was 100%, with a recurrence rate of 6%. A large defect, failure of localization of the defect, or other co-morbid conditions such as chronic cough may be the most likely causes of recurrence of leak. CONCLUSION: Accurate localization of the site of lesion using a high-resolution computed tomography (CT) scan with magnetic resonance imaging (MRI) and confirmation of the site of leak by intraoperative Valsalva maneuver along with multilayered closure of the dural defect and post-operative lumbar drain appear to be essential for the successful endoscopic repair of CSF rhinorrhea. PMID- 26878001 TI - Audiological Outcome of Classical Adenoidectomy versus Endoscopically-Assisted Adenoidectomy using a Microdebrider. AB - INTRODUCTION: The aim of this study was to evaluate audiological outcomes following adenoidectomy by the classical method and by endoscopically-assisted adenoidectomy using a powered instrument (microdebrider). MATERIALS AND METHODS: This study was conducted in a tertiary care center. It included 40 patients divided into two equal groups of 20 each. Group-A patients underwent classical adenoidectomy, while Group-B patients were subjected to endoscopically-assisted adenoidectomy using a microdebrider. Hearing outcome was measured by post operative pure-tone audiometry and tympanometry. RESULTS: The post-operative average air-bone gap (ABG) was reduced from 19.6 dB to 11.8 dB in Group A and from 17.6 dB to 8.7 dB in Group B (P=0.010). There was reversal of tympanometric curves from type-B and type-C to type-A in 55% of the patients in Group A, while type-A curve was seen in 90% cases in Group B in the post-operative period. CONCLUSION: Audiological outcomes of endoscopically-assisted adenoidectomy using a microdebrider were superior compared with classical adenoidectomy. PMID- 26878003 TI - Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds. AB - INTRODUCTION: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. MATERIALS AND METHODS: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. RESULTS: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). CONCLUSION: Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area. PMID- 26878004 TI - MTA1 Expression in Benign and Malignant Salivary gland Tumors. AB - INTRODUCTION: Salivary gland tumors (SGTs) are important parts of human neoplasms. The most common SGT is pleomorphic adenoma and the most common malignant SGTs are mucoepidermoid carcinoma and adenoid cystic carcinoma (ACC). Metastasis-associated genes 1 (MTA1), a member of the nucleosome remodeling and histone deacetylation complex, is one newly discovered gene which recruits histone deacetylation, causing ATP-dependent chromosome remodeling, and regulating transcription. MTA1 had been shown to be overexpressed in malignant tumors with the enhancement of invasion and metastasis. MATERIALS AND METHODS: Fifty-six samples of salivary gland tumors from the Khalili Hospital archive, including 20 cases of pleomorphic adenoma, 17 cases of mucoepidermoid carcinoma, 19 cases of ACC, and 23 cases of normal salivary gland tissues were chosen for immunohistochemical analysis of MTA1. RESULTS: MTA1 expression in the malignant tumors was significantly higher than that in pleomorphic adenoma (P<0.001), and higher in pleomorphic adenoma than the normal salivary glands(P< 0.001). In total, 69.6% of normal salivary gland tissues showed MTA1, but all cases of salivary gland tumors were positive for MTA1. High nuclear expression of MTA1 was detected in 83.3% (30/36) of the malignant salivary gland tumors and 45% (9/20) of pleomorphic adenoma, while low MTA1 expression was seen in all of the normal salivary gland tissues. No statistically significant correlation was found between MTA1 protein expression and any clinicopathological features (P>0.05). CONCLUSION: Our findings demonstrate that MTA1 was significantly overexpressed in malignant salivary gland neoplasm in comparison to a lower level in benign pleomorphic adenoma, suggesting that MTA1 protein might be involved in carcinogenesis. PMID- 26878005 TI - Effects of Tonsil size on Pulmonary Function test Results after Tonsillectomy in Children. AB - INTRODUCTION: Adenotonsillar hypertrophy is a typical cause of surgery in children. Evaluation and identification of patients as potential candidates tonsillectomy is a primary concern for otolaryngologists. This study focuses on the results of pulmonary function tests (PFTs) after tonsillectomy in children. MATERIALS AND METHODS: This cross-sectional study examined 50 patients suffering from tonsillar hypertrophy in 2013. Full details and results of otolaryngology examinations were recorded. Moreover, patients were examined with respect to forced inspiratory flow at 50% of vital capacity (FIF50%), forced expiratory flow at 50% of vital capacity (FEF50%), forced expiratory volume in 1 second (FEV1)/peak expiratory flow rate (PEFR), and FEV1/forced expired volume in 0.5 seconds (FEV0.5) before and after surgery using spirometry. All data were analyzed using SPSS Software (version 19), and central descriptive measures, and data were compared by performing T-test and Chi-square tests. RESULTS: According to tonsil size, patients were distributed as follows: 18 patients (36%) with +1 tonsil size, 18 patients (36%) with +2 tonsil size, and seven patients (14%) with +3 tonsil size, and seven patients (14%) with +4 tonsil size. Thirty-three (66%) and 17 patients (34%) were female and male, respectively, with a mean of age of 9.7[Formula: see text]2.97 years (range, 7-18 years). Seventy-eight percent of patients were aged 10 years or less. Moreover, 25 patients (50%), 17 patients (34%), and eight patients (16%), respectively, reported obstructive symptoms, recurrent tonsillitis, and both symptoms. In patients with +3 and +4 tonsil size, spirometric parameters indicated relief of symptoms of obstruction. Only in patients with +4 tonsil size were the changes statistically significant. CONCLUSION: Tonsillectomy can relieve obstructive symptoms in patients with tonsils larger than +3 to a great extent. Additionally, spirometry can identify patients with +3 and +4 tonsils who do not have clinical signs of an obstructive upper airway. PMID- 26878006 TI - An Unusual Case of Cauda Equina Secondary to Spinal Metastasis of Thyroid Cancer. AB - INTRODUCTION: Cauda equina secondary to metastatic follicular thyroid cancer of the lumbosacral area is a rare entity. CASE REPORT: We report an unusual case of a 52-year-old male who presented with backache, lower limb weakness, and perianal numbness. A CT-scan of the lumbosacral area showed an enhancing mass at the L4, L5 and S1 vertebrae. Histopathology after excision revealed a metastatic thyroid cancer. Hence, a CT scan of the neck and chest was performed which showed a nodule in the left lobe of the thyroid and a mass in the left chest wall. A total thyroidectomy and excision of the chest wall lesion was undergone, which was diagnosed as a follicular carcinoma of the thyroid. CONCLUSION: Metastatic workup of spinal metastasis should include evaluation of the thyroid gland. PMID- 26878007 TI - Pleomorphic Adenoma of the Larynx: A Case Report. AB - INTRODUCTION: Pleomorphic adenomas are tumors mostly originating from salivary glands. These lesions in the larynx are very rare. CASE REPORT: We report a rare case of pleomorphic adenoma that originated from the mucosal lining, just above the glottic area at the level of the laryngeal ventricle in a 55-year-old female patient. The tumor could not be palpated easily but was observed in the CT scan. We resected the large and firm tumor using trans hyoid pharyngotomy as the surgical approach. CONCLUSION: Pleomorphic adenoma in the ventricle of the larynx is an extremely rare lesion. Trans-hyoid pharyngotomy can have good results as the surgical approach in removing such lesions. PMID- 26878008 TI - Inflammatory Myofibroblastic Tumor of the Larynx:A Case Report. AB - INTRODUCTION: Inflammatory myofibroblastic pseudotumors are initially described in the lung and various extrapulmonary sites such as the orbits, palatine tonsils, ears, gingiva, pterygomaxillary space, and periodontal tissues. These tumors rarely involve the larynx and predilection to the glottis occurs in an indolent manner. CASE REPORT: This case describes a laryngeal myofibroblastic tumor in a 46-year-old woman who presented with an aggressive tumor that extended to the floor of the mouth and the base of the tongue. Extended supraglottic laryngectomy was undertaken for the patient. The diagnosis was spindle cell proliferation with dense lymphoplasma cell infiltration compatible with inflammatory myofibroblastic tumor (Inflammatory pseudotumor or plasma cell granuloma). Definitive diagnosis was achieved with immunohistochemical (IHC) staining. CONCLUSION: We believe that further IHC studies are required to define the true nature of these tumors especially for those that behave in an aggressive pattern. PMID- 26878009 TI - Chronic Invasive Fungal Granuloma-A Diagnostic Dilemma in an Immunocompetent Host. AB - INTRODUCTION: Invasive fungal sinusitis, though considered to be rare entity, is nowadays frequently encountered, not only in immunocompromised patients but also in immunocompetent patients. The changing prevalence towards immunocompetent hosts is due to the indiscriminate usage of broad spectrum antibiotics, steroids, and immunosuppressive drugs. Diagnosing invasive fungal sinusitis should not pose any difficulty to both the clinician [a whitish colour secretion in elderly Diabetics, and CT Scan PNS showing concretion in the sinus along with destruction of the surrounding bone] and to the pathologist; however, when the invasive fungal sinus infection presents in a form of a granuloma then its diagnosis imposes a challenge to medical professionals. CASE REPORT: We are presenting a case study,which consists of 3 cases of chronic invasive fungal sinus infection.Two patients were treated for tuberculoma and had completed a course of Anti Koch's Treatment and one patient was given a trial of broad spectrum antibiotics and steroids.Eventually all cases were diagnosed as a chronic invasive form of fungal granuloma (CIFG). CONCLUSION: CIFG of the paranasal sinuses is seen in immunocompetent hosts, especially those that are in the 2nd and 3rd decades of their lives. Gradually progressive proptosis is the primary presenting symptom. MRI scanning is a better imaging modality compared to CT scanning. Routine H&E staining may prove inadequate and special stains such as the GMS stain should be employed in the slightest doubt of a fungal aetiology. A team approach towards patients is paramount for early diagnosis and timely medical and surgical intervention. PMID- 26878010 TI - Polymorphisms in NOS3, MTHFR, APOB and TNF-alpha Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients. AB - BACKGROUND: Atherosclerosis is a complex multifocal arterial disease involving interactions between multiple genetic and environmental factors. OBJECTIVES: In the present study, we investigated the possible association between NOS3 (rs1799983), MTHFR (rs1801133), APOB (rs5742904) and TNF-alpha (rs361525) polymorphisms and the risk of coronary atherosclerotic lesions in Iranian patients. PATIENTS AND METHODS: In the case-control study, 108 patients with coronary atherosclerosis disease and 95 control subjects with no family history of cardiovascular disease were enrolled. Genotypes for NOS3, MTHFR, APOB and TNF alpha polymorphisms were identified using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: We specifically detected the NOS3 TT genotype in 12 patients (11.11%) and did not find the same genotype in any of the controls. The frequencies of T allele in patients and the controls were 24% and 17.8%, respectively. The prevalence of the MTHFR TT genotype was 16.7% in patients and 2.2% in control groups. The prevalence of the APOB-100 (R3500Q) mutation in this patient population was 0%. The frequency of the A allele in the TNF-alpha gene was 11.1% and 11% in patients and controls, respectively, and the AA genotype was undetected. CONCLUSIONS: Our results show a significant association of NOS3 and MTHFR gene polymorphisms with coronary atherosclerotic lesions. Therefore, these variants might influence the risk of coronary artery disease, specifically in the Iranian population. PMID- 26878011 TI - Higher Cognitive Performance Is Prospectively Associated with Healthy Dietary Choices: The Maine Syracuse Longitudinal Study. AB - OBJECTIVES: Few studies have examined whether cognitive function predicts dietary intake. The majority of research has focused on how diet can influence cognitive performance or risk for cognitive impairment in later life. The aim of this study was to examine prospective relationships between cognitive performance and dietary intake in participants of the Maine-Syracuse Longitudinal Study. DESIGN: A prospective study with neuropsychological testing at baseline and nutritional assessments measured a mean of 18 years later. SETTING: Community-dwelling individuals residing in central New York state. PARTICIPANTS: 333 participants free of dementia and stroke. MEASUREMENTS: The Wechsler Adult Intelligence Scale (WAIS) was assessed at baseline and dietary intake was measured using the Nutrition and Health Questionnaire. RESULTS: Higher WAIS Scores at baseline were prospectively associated with higher intakes of vegetables, meats, nuts and legumes, and fish, but inversely associated with consumption of total grains and carbonated soft drinks. After adjustment for sample selection, socioeconomic indicators, lifestyle factors (smoking and physical activity), and cardiovascular risk factors, the relations between higher cognitive performance and greater consumption of vegetables, meat, and fish, and lower consumption of grains remained significant. CONCLUSION: These data suggest that cognition early in life may influence dietary choices later in life. PMID- 26878012 TI - Clinical significance of serum CA15-3 as a prognostic parameter during follow-up periods in patients with breast cancer. AB - PURPOSE: To assess the relationship between the kinetics of the serum CA15-3 level and the five-year disease-free survival rate of breast cancer patients. METHODS: The subjects of this study, 297 women who were diagnosed with breast cancer, were the subset of patients operated on at Kosin University Gospel Hospital from January 2008 to December 2010. We evaluated the change of serum CA15-3 levels during outpatient follow-up period. The changing patterns of serum CA15-3 level were divided into 5 categories; surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no change. Clinicopathologic factors were evaluated for each group. RESULTS: The number of patients in surge without decline, surge with incidental decline, decline without surge, decline with incidental surge, and no changes groups were 30 (10.1%), 85 (28.6%), 80 (26.9%), 73 (24.6%), and 29 (9.7%), respectively. The clinicopathologic characteristics were not significantly different among these groups. The log rank test found that 5-year disease-free survival rate according to the kinetics of serum CA15-3 levels were significant (P = 0.004) particularly for the surge without decline group. CONCLUSION: According to the findings of this study, the surge without incidental decline pattern of serum CA15-3 levels during the follow-up period is associated with poor prognosis. Significant association was found among changing patterns of serum CA15-3 levels and breast cancer recurrence rate. PMID- 26878013 TI - A simple pancreaticojejunostomy technique for hard pancreases using only two transpancreatic sutures with buttresses: a comparison with the previous pancreaticogastrostomy and dunking methods. AB - PURPOSE: In this study, we introduced a novel technique, the pancreaticojejunostomy (PJ), which uses only two transpancreatic sutures with buttresses (PJt), and compared the surgical outcomes with previously used methods, especially for hard pancreases. METHODS: A total of 101 patients who underwent pancreaticoduodenectomy with hard pancreases were enrolled and divided into 3 groups according to the method of pancreaticoenteric anastomosis: 30 patients (29.7%) underwent the conventional dunking method (Du), 31 patients (30.7%) underwent pancreaticogastrostomy using transpancreatic sutures (PGt) and 40 patients (39.6%) underwent PJ using transpancreatic sutures (PJt). The surgical outcomes were compared according to the type of anastomosis to analyze the feasibility and ease of each technique. RESULTS: The overall operative time was shorter in the PJt group (325.1 +/- 63.8 minutes) than in the PGt group (367.3 +/- 70.5 minutes) or the Du group (412.0 +/- 38.2 minutes, P < 0.001). In terms of pancreaticoenteric anastomosis time, it was also shorter in the PJt group (10.3 +/- 3.5 minutes) than in the Du group (20.7 +/- 0.7 minutes) or the PGt group (16.8 +/- 5.4 minutes, P = 0.005). Significant postoperative pancreatic fistula (POPF) developed in 2 cases (6.7%) in the Du group, whereas there were no POPF cases in the PGt or PJt groups (P = 0.086). Overall postoperative morbidities occurred in 31 cases (30.7%), and there were no significant differences among the 3 groups (P = 0.692). CONCLUSION: The novel PJ technique, which uses only two transpancreatic sutures with buttresses, is a very simple, easy and secure method for hard pancreases and can be performed in a shorter amount of time compared with conventional methods. PMID- 26878014 TI - One-year experience with single incision laparoscopic cholecystectomy in a single center: without the use of inverse triangulation. AB - PURPOSE: Single incision laparoscopic cholecystectomy (SILC) is generally performed with the use of inverse triangulation. In this study, we performed 3 channel or 4-channel SILC without the use of inverse triangulation. We evaluated the adequacy and feasibility of SILC using our surgical method. METHODS: We retrospectively reviewed our series of 309 SILCs performed between March 2014 and February 2015. RESULTS: Among 309 SILCs, male were 148 and female were 161 patients, mean age was 48.7 +/- 15.3 years old and mean body mass index was 24.8 +/- 3.8 kg/m(2). Forty patients had previously undergone abdominal surgery including 6 cases of upper abdominal surgery. SILC after percutaneous transhepatic gallbladder (GB) drainage was completed in 8.7% of cases. There were 10 cases of emergency SILC. SILC was performed for noncomplicated GB including symptomatic GB stone and polyp in 66.7% of cases, acute cholecystitis in 33.3%. Overall, 96.8% of procedures were successfully completed without additional port. The reason for addition of an extra port or open conversion included technical difficulties due to severe adhesion and bleeding. The mean operating time was 60.7 +/- 22.3 minutes. The overall complication rate was 4.8%: 9 patients of wound seroma, 1 case of bile leakage from GB bed, 4 cases of intra-abdominal abscess or fluid collection, and 1 case of incisional hernia were developed. There was no case of common bile duct injury. CONCLUSION: Our surgical method of SILC without the use of inverse triangulation is safe, feasible and effective technique. PMID- 26878015 TI - Effects of intensive nutrition education on nutritional status and quality of life among postgastrectomy patients. AB - PURPOSE: We examined the effects of 3 months of intensive education (IE) after hospital discharge compared to conventional education (CE) on nutritional status and quality of diet and life among South Korean gastrectomy patients. METHODS: The study was conducted among 53 hospitalized gastrectomy in-patients (IE group, n = 28; CE group, n = 25) at Kyung Hee University Hospital at Gangdong. Baseline data were collected from electronic medical records and additional information was gathered via anthropometric measurements, assessment of nutritional status through a patient-generated, subjective global assessment (PG-SGA), diet assessment, and measures of self-efficacy and satisfaction with meals for 3 months following hospital discharge. RESULTS: Total PG-SGA scores were significantly higher in the CE group than in the IE group at 3-week post discharge (5.2 in the IE group vs. 10.4 in the CE group, P < 0.001), with higher scores indicating a greater severity of malnutrition. Energy intake over the 3 months increased in both the IE group (from 1,390 to 1,726 kcal/day) and the CE group (from 1,227 to 1,540 kcal/day). At 3-week post-discharge, the IE group had significantly higher daily protein and fat intake (P < 0.05). Self-efficacy improved in each category (P < 0.001), except for 'difficulty eating adequate food'. When assessing satisfaction with meals, there was a difference in the 'satisfaction with the current meal size' (P < 0.001) and 'satisfaction with the menu content' (P < 0.001). CONCLUSION: Nutritional status among gastrectomy patients in the IE group improved. Relative to the CE control, the IE group demonstrated improved self-efficacy and meal satisfaction 3-week post-discharge. PMID- 26878016 TI - Clinical utility of balloon expulsion test for functional defecation disorders. AB - PURPOSE: I investigated the diagnostic accuracy of balloon expulsion test (BET) with various techniques to find out the most appropriate method, and tried to confirm its clinical utility in diagnosing functional defecation disorders (FDD) in constipated patients. METHODS: Eighty-seven patients constituted the study population. FDD was defined when patients had at least two positive findings in defecography, manometry, and electromyography. BET was done 4 times in each patient with 2 different positions and 2 different volumes. The positions were seated position (SP) and left lateral decubitus position (LDP). The volumes were fixed volume (FV) of 60 mL and individualized volume with which patient felt a constant desire to defecate (CDV). The results of BETs with 4 different settings (LDP-FV, LDP-CDV, SP-FV, and SP-CDV) were statistically compared and analyzed. RESULTS: Of 87 patients, 23 patients (26.4%) had at least two positive findings in 3 tests and thus were diagnosed to have FDD. On receiver operating characteristic curve analysis, area under curve was highest in BET with SP-FV. With a cutoff value of 30 seconds, the specificity of BET with SP-FV was 86.0%, sensitivity was 73.9%, negative predictive value was 89.8%, positive predictive value was 65.4%, and accuracy rate was 82.8% for diagnosing FDD. CONCLUSION: SP FV is the most appropriate method for BET. In this setting, BET has a diagnostic accuracy sufficient to identify constipated patients who do not have FDD. Patients with negative results in BET with SP-FV may not need other onerous tests to exclude FDD. PMID- 26878017 TI - A new risk-scoring model for predicting 30-day mortality after repair of abdominal aortic aneurysms in the era of endovascular procedures. AB - PURPOSE: To propose a new, multivariable risk-scoring model for predicting 30-day mortality in individuals underwent repair of abdominal aortic aneurysms (AAA). METHODS: Four hundred eighty-five consecutive patients who underwent AAA repair from January 2000 to December 2010 were included in the study. Univariate and multivariate analyses were performed to evaluate the risk factors, and a risk scoring model was developed. RESULTS: Multivariate analysis identified three independent preoperative risk factors associated with mortality, and a risk scoring model was created by assigning an equal value to each factor. The independent predictors were location of the AAA, rupture of AAA, and preoperative pulmonary dysfunction. The multivariable regression model demonstrated moderate discrimination (c statistic, 0.811) and calibration (Hosmer-Lemeshow test, P = 0.793). The observed mortality rate did not differ significantly from that predicted by our risk-scoring model. CONCLUSION: Our risk-scoring model has excellent ability to predict 30-day mortality after AAA repair, and awaits validation in further studies. PMID- 26878018 TI - Minimally invasive surgery for congenital cystic adenomatoid malformations - early experience. AB - PURPOSE: The aim of this study is to present our experience with minimally invasive surgery (MIS) for congenital cystic adenomatoid malformations (CCAMs). METHODS: The medical records of infants under 2 years of age who underwent operation for a CCAM from 2009 to 2014 were retrospectively reviewed. RESULTS: MIS (9 of thoracoscopy and 1 of laparoscopy) was performed for 10 infants (male:female = 7:3) with CCAM. CCAM were discovered prenatally around gestational age of 24.7 weeks. The median gestational age was 38.6 weeks, and the median body weight was 2,817.5 g. None had respiratory distress after birth. The median age at the time of operation was 0.94 years (range: 8 days-1.66 years). Two underwent the operation during the neonatal period; one because of a coexisting large esophageal duplication cyst and the other due to diagnostic uncertainty. While awaiting operation, 5 of CCAM had grown without respiratory symptoms, and 2 infants had experienced pneumonia. The mean operative time was 98 minutes (range: 70-227 minutes), and there were no conversions or perioperative complications. The infants resumed enteral feeding within 2 days and were discharged within 7 days, except for 1 infant who underwent esophageal duplication cyst excision. During the follow-up period, there were no cases of either remnant lesions or respiratory symptoms. CONCLUSION: MIS for CCAMs is safe and feasible, with excellent cosmesis and short hospital stays. Increasing experience with various MIS procedures will widen the indications for MIS in lung pathology. PMID- 26878019 TI - Laparoscopic completion total gastrectomy for remnant gastric cancer following pancreaticoduodenectomy for bile duct cancer: a case report. AB - Laparoscopic completion total gastrectomy following pancreaticoduodenectomy (PD) has not been reported. A 73-year-old male who underwent PD 25 years ago for distal common bile duct cancer visited a surgical department for remnant gastric cancer. A previous reconstruction was performed with pancreaticojejunostomy (PJ), gastrojejunostomy and Braun anastomosis, i.e., jejunojejunostomy (JJ), between the afferent and efferent jejunal limb to prevent bile reflux into the remnant stomach. Adhesiolysis was initially performed to secure the surgical view. Lymph node dissections around the splenic artery, splenic hilum, celiac axis, left gastric artery, and common hepatic artery were performed. The PJ site was well visualized and safely preserved. Esophagojejunostomy was performed with an OrVil system. Specimen retrieval, Roux-limb preparation and JJ were performed through an extended umbilicus trocar site. A final pathologic examination revealed a 5.5 cm serosa-exposed tumor (T4a) without lymph node metastasis. The patient was discharged on postoperative day 7 without any complications. PMID- 26878020 TI - Novel method of laparoendoscopic single-site and natural orifice specimen extraction for live donor nephrectomy: single-port laparoscopic donor nephrectomy and transvaginal graft extraction. AB - Laparoscopic live donor nephrectomy (DN) has been established as a useful alternative to the traditional open methods of procuring kidneys. To maximize the advantages of the laparoendoscopic single-site (LESS) method, we applied natural orifice specimen extraction to LESS-DN. A 46-year-old woman with no previous abdominal surgery history volunteered to donate her left kidney to her husband and underwent single-port laparoscopic DN with transvaginal extraction. The procedure was completed without intraoperative complications. The kidney functioned well immediately after transplantation, and the donor and recipient were respectively discharged 2 days and 2 weeks postoperatively. Single-port laparoscopic DN and transvaginal graft extraction is feasible and safe. PMID- 26878021 TI - CAD/CAM splint based on soft tissue 3D simulation for treatment of facial asymmetry. AB - BACKGROUND: Most cases of facial asymmetry involve yaw deformity, and determination of the yaw correction level is very difficult. METHODS: We use three-dimensional soft tissue simulation to determine the yaw correction level. This three-dimensional simulation is based on the addition of cephalometric prediction to gradual yaw correction. Optimal yaw correction is determined visually, and an intermediate splint is fabricated with computer-aided design and computer-aided manufacturing. Application of positioning devices and the performance of horseshoe osteotomy are advisable. RESULTS: With this procedure, accurate repositioning of jaws was confirmed and patients obtained fairly good facial contour. CONCLUSIONS: This procedure is a promising method for a widespread, predictable treatment of facial asymmetry. PMID- 26878022 TI - Altered Hemodynamics in the Embryonic Heart Affects Outflow Valve Development. AB - Cardiac valve structure and function are primarily determined during early development. Consequently, abnormally-formed heart valves are the most common type of congenital heart defects. Several adult valve diseases can be backtracked to abnormal valve development, making it imperative to completely understand the process and regulation of heart valve development. Epithelial-to-mesenchymal transition (EMT) plays an important role in the development of heart valves. Though hemodynamics is vital to valve development, its role in regulating EMT is still unknown. In this study, intracardiac hemodynamics were altered by constricting the outflow tract (OFT)/ventricle junction (OVJ) of HH16-17 (Hamilton and Hamburger (HH) Stage 16-17) chicken embryos, ex ovo for 24 h. The constriction created an increase in peak and time-averaged centerline velocity along the OFT without changes to volumetric flow or heart rate. Computational fluid dynamics was used to estimate the level of increased spatially-averaged wall shear stresses on the OFT cushion from AMIRA reconstructions. OFT constriction led to a significant decrease in OFT cushion volume and the number of invaded mesenchyme in the OFT cushion. qPCR analysis revealed altered mRNA expression of a representative panel of genes, vital to valve development, in the OFT cushions from banded hearts. This study indicates the importance of hemodynamics in valve development. PMID- 26878023 TI - Proteomic Analysis of Pathogenic Fungi Reveals Highly Expressed Conserved Cell Wall Proteins. AB - We are presenting a quantitative proteomics tally of the most commonly expressed conserved fungal proteins of the cytosol, the cell wall, and the secretome. It was our goal to identify fungi-typical proteins that do not share significant homology with human proteins. Such fungal proteins are of interest to the development of vaccines or drug targets. Protein samples were derived from 13 fungal species, cultured in rich or in minimal media; these included clinical isolates of Aspergillus, Candida, Mucor, Cryptococcus, and Coccidioides species. Proteomes were analyzed by quantitative MSE (Mass Spectrometry-Elevated Collision Energy). Several thousand proteins were identified and quantified in total across all fractions and culture conditions. The 42 most abundant proteins identified in fungal cell walls or supernatants shared no to very little homology with human proteins. In contrast, all but five of the 50 most abundant cytosolic proteins had human homologs with sequence identity averaging 59%. Proteomic comparisons of the secreted or surface localized fungal proteins highlighted conserved homologs of the Aspergillus fumigatus proteins 1,3-beta-glucanosyltransferases (Bgt1, Gel1 4), Crf1, Ecm33, EglC, and others. The fact that Crf1 and Gel1 were previously shown to be promising vaccine candidates, underlines the value of the proteomics data presented here. PMID- 26878024 TI - [Barriers to adherence and retention in public and private healthcare according to patients and health workers]. AB - INTRODUCTION: The National Program of AIDS guarantees universal access to antiretroviral medication, yet people receiving treatment through the public healthcare system do not achieve an undetectable viral load in the same rate than patients in the private system. This qualitative study aims to identify factors associated with adherence and retention in the HIV-cascade of care at public and private setting from Buenos Aires, based on patients and healthcare workers' perceptions. METHODS: Qualitative data from 12 semi-structured interviews with key informants and 4 focus groups of patients and healthcare workers from the public and private systems were recorded. Transcripts were coded and analyzed, using the QRS Nvivo9(r) software for qualitative data analysis, into set themes on adherence. RESULTS: Patients and healthcare workers of both systems agree on the importance of HIV-related stigma, professional-patient relationship and communication, and the division of treatment-related responsibilities as fundamental aspects for adherence and retention in the HIV-cascade of care. Differences in the manner these factors interact were observed between healthcare systems. Structural barriers are presented as the main adherence barrier in the public system. DISCUSSION: The need for interventions focused on the doctor patient dyad considering the features of each healthcare is highlighted in order to facilitate patient engagement in adherence. PMID- 26878026 TI - Prediction in the Processing of Repair Disfluencies. AB - Imagine a speaker who says "Turn left, uh I mean..." Before hearing the repair, the listener is likely to anticipate the word "right" based on the context, including the reparandum "left." Thus, even though the reparandum is not intended as part of the utterance, the listener uses it as information to predict the repair. The issue we explore in this article is how prediction operates in disfluency contexts. We begin by describing the Overlay model of disfluency comprehension, which assumes that the listener identifies a reparandum as such only after a repair is encountered which creates a local ungrammaticality. The Overlay model also allows the reparandum to influence subsequent processing, because the reparandum is not deleted from the final representation of the sentence. A somewhat different model can be developed which assumes a more active, anticipatory process for resolving repair disfluencies. On this model, the listener might predict the likely repair when the speaker becomes disfluent, or even identify a reparandum if the word or word string seems inconsistent with the speaker's intention. Our proposal is that the prediction can be made using the same mechanism involved in the processing of contrast, in which a listener uses contrastive prominence to generate likely alternates (the contrast set). We suggest that these two approaches to disfluency processing are not inconsistent: Successful repair processing requires listeners to use statistical and linguistic evidence to identify a reparandum and to integrate the repair, and the lingering of the reparandum is due to the coexistence in working memory of the reparandum, the repair, and unselected members of the contrast set. PMID- 26878027 TI - Efficient Multiterminal Spectrum Splitting via a Nanowire Array Solar Cell. AB - Nanowire-based solar cells opened a new avenue for increasing conversion efficiency and rationalizing material use by growing different III-V materials on silicon substrates. Here, we propose a multiterminal nanowire solar cell design with a theoretical conversion efficiency of 48.3% utilizing an efficient lateral spectrum splitting between three different III-V material nanowire arrays grown on a flat silicon substrate. This allows choosing an ideal material combination to achieve the proper spectrum splitting as well as fabrication feasibility. The high efficiency is possible due to an enhanced absorption cross-section of standing nanowires and optimization of the geometric parameters. Furthermore, we propose a multiterminal contacting scheme that can be fabricated with a technology close to standard CMOS. As an alternative we also consider a single power source with a module level voltage matching. These new concepts open avenues for next-generation solar cells for terrestrial and space applications. PMID- 26878028 TI - On-Demand Coupling of Electrically Generated Excitons with Surface Plasmons via Voltage-Controlled Emission Zone Position. AB - The ability to confine and manipulate light below the diffraction limit is a major goal of future multifunctional optoelectronic/plasmonic systems. Here, we demonstrate the design and realization of a tunable and localized electrical source of excitons coupled to surface plasmons based on a polymer light-emitting field-effect transistor (LEFET). Gold nanorods that are integrated into the channel support localized surface plasmons and serve as nanoantennas for enhanced electroluminescence. By precise spatial control of the near-infrared emission zone in the LEFET via the applied voltages the near-field coupling between electrically generated excitons and the nanorods can be turned on or off as visualized by a change of electroluminescence intensity. Numerical calculations and spectroscopic measurements corroborate significant local electroluminescence enhancement due to the high local density of photonic states in the vicinity of the gold nanorods. Importantly, the integration of plasmonic nanostructures hardly influences the electrical performance of the LEFETs, thus, highlighting their mutual compatibility in novel active plasmonic devices. PMID- 26878029 TI - Measurement of Resting Energy Metabolism in Mice Using Oxymax Open Circuit Indirect Calorimeter. AB - Indirect calorimeter is a powerful tool to monitor resting energy metabolism through the measurement of oxygen (O2) consumption and carbon dioxide (CO2) production. From the measurement of VO2 and VCO2, the respiratory exchange ratio (RER) can be calculated to assess energy fuel utilization and energy expenditure (Evan et al., 2012). Previously, indirect calorimeter has been widely used in metabolic disease research in mice to reveal the potential roles of specific genes or treatments in regulating energy metabolism (for example: Bi et al., 2014; Feng et al., 2014). Here, we described a protocol to evaluate the resting energy metabolism of C57BL/6 mice during dark and light cycles using the Oxymax Open Circuit indirect calorimeter. PMID- 26878030 TI - Parents' Experiences With Ultrasound During Pregnancy With a Lethal Fetal Diagnosis. AB - This longitudinal naturalistic study sought to describe parent experiences of ultrasounds during pregnancies with lethal fetal diagnoses (LFDs). We interviewed 16 mothers and 14 partners twice during pregnancy and twice after birth and death of their infant. Parents reported that ultrasound providers had a profound impact on their experiences with LFDs. Within three stages of pregnancy (pre-diagnosis, learning the diagnosis, and living with the diagnosis), themes of optimistic expectation, hearing bad news, need to know, and time with baby emerged. The dynamics of interactions with ultrasound providers included differing goals and expectations, and compatibility of interactions. These interactions were either satisfying or added to parents' burden. Ultrasound providers have the opportunity to share valuable knowledge and facilitate understanding and precious time with the baby. Providers of obstetrical care can improve communication with parents with LFDs at critical time periods by matching their interaction to parents' needs. PMID- 26878031 TI - Alternating dual updates algorithm for X-ray CT reconstruction on the GPU. AB - Model-based image reconstruction (MBIR) for X-ray computed tomography (CT) offers improved image quality and potential low-dose operation, but has yet to reach ubiquity in the clinic. MBIR methods form an image by solving a large statistically motivated optimization problem, and the long time it takes to numerically solve this problem has hampered MBIR's adoption. We present a new optimization algorithm for X-ray CT MBIR based on duality and group coordinate ascent that may converge even with approximate updates and can handle a wide range of regularizers, including total variation (TV). The algorithm iteratively updates groups of dual variables corresponding to terms in the cost function; these updates are highly parallel and map well onto the GPU. Although the algorithm stores a large number of variables, the "working size" for each of the algorithm's steps is small and can be efficiently streamed to the GPU while other calculations are being performed. The proposed algorithm converges rapidly on both real and simulated data and shows promising parallelization over multiple devices. PMID- 26878025 TI - Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism. AB - In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID- 26878032 TI - Contribution of substantia nigra glutamate to prediction error signals in schizophrenia: a combined magnetic resonance spectroscopy/functional imaging study. AB - BACKGROUND: Because dopamine neurons signal a mismatch between expected and actual reward called prediction error (PE), aberrant PE signals in schizophrenia have been attributed to known dopaminergic abnormalities. However, dysfunction of N-methyl-D-aspartate receptors on cortical gamma-aminobutyric acid neurons, as hypothesized in schizophrenia, could lead to excess glutamate release in the substantia nigra (SN) and affect reward processing. AIMS: The aim of this study was to investigate the contribution of SN glutamate to PE signals in healthy controls (HC) and patients with schizophrenia (SZ). METHODS: We recruited 22 medicated SZ and 19 HC. We obtained (1) functional magnetic resonance imaging during a probabilistic monetary reward task to assess PE-related blood oxygen level-dependent (BOLD) signal and (2) magnetic resonance spectroscopy to measure Glx (glutamate+glutamine) in the SN. To identify group differences in regions where the BOLD signal varies as a function of PE, we analyzed PEs generated during the task as parametric modulators of reward delivery. Finally, we examined the correlation of PE-related BOLD signal and SN Glx in each group. RESULTS: Relative to HC, PE-related BOLD signals in SZ were significantly different in the midbrain/SN and ventral striatum. In SZ, SN Glx was significantly elevated. In HC, but not in SZ, PE-related BOLD signal in SN was positively correlated with SN Glx. CONCLUSIONS: These results suggest a role of glutamate in the neural coding of PE in controls. They indicate that glutamatergic dysfunction might contribute to abnormal PE coding in schizophrenia, suggesting the use of glutamate-targeted approaches to improve these deficits. PMID- 26878033 TI - ELMO1 has an essential role in the internalization of Salmonella Typhimurium into enteric macrophages that impacts disease outcome. AB - BACKGROUNDS AND AIMS: 4-6 million people die of enteric infections each year. After invading intestinal epithelial cells, enteric bacteria encounter phagocytes. However, little is known about how phagocytes internalize the bacteria to generate host responses. Previously, we have shown that BAI1 (Brain Angiogenesis Inhibitor 1) binds and internalizes Gram-negative bacteria through an ELMO1 (Engulfment and cell Motility protein 1)/Rac1-dependent mechanism. Here we delineate the role of ELMO1 in host inflammatory responses following enteric infection. METHODS: ELMO1-depleted murine macrophage cell lines, intestinal macrophages and ELMO1 deficient mice (total or myeloid-cell specific) was infected with Salmonella enterica serovar Typhimurium. The bacterial load, inflammatory cytokines and histopathology was evaluated in the ileum, cecum and spleen. The ELMO1 dependent host cytokines were detected by a cytokine array. ELMO1 mediated Rac1 activity was measured by pulldown assay. RESULTS: The cytokine array showed reduced release of pro-inflammatory cytokines, including TNF-alpha and MCP-1, by ELMO1-depleted macrophages. Inhibition of ELMO1 expression in macrophages decreased Rac1 activation (~6 fold) and reduced internalization of Salmonella. ELMO1-dependent internalization was indispensable for TNF-alpha and MCP-1. Simultaneous inhibition of ELMO1 and Rac function virtually abrogated TNF-alpha responses to infection. Further, activation of NF kappaB, ERK1/2 and p38 MAP kinases were impaired in ELMO1-depleted cells. Strikingly, bacterial internalization by intestinal macrophages was completely dependent on ELMO1. Salmonella infection of ELMO1-deficient mice resulted in a 90% reduction in bacterial burden and attenuated inflammatory responses in the ileum, spleen and cecum. CONCLUSION: These findings suggest a novel role for ELMO1 in facilitating intracellular bacterial sensing and the induction of inflammatory responses following infection with Salmonella. PMID- 26878034 TI - Development of a subjective cognitive decline questionnaire using item response theory: a pilot study. AB - BACKGROUND: Subjective cognitive decline (SCD) may indicate unhealthy cognitive changes, but no standardized SCD measurement exists. This pilot study aims to identify reliable SCD questions. METHODS: 112 cognitively normal (NC, 76+/-8 years, 63% female), 43 mild cognitive impairment (MCI; 77+/-7 years, 51% female), and 33 diagnostically ambiguous participants (79+/-9 years, 58% female) were recruited from a research registry and completed 57 self-report SCD questions. Psychometric methods were used for item-reduction. RESULTS: Factor analytic models assessed unidimensionality of the latent trait (SCD); 19 items were removed with extreme response distribution or trait-fit. Item response theory (IRT) provided information about question utility; 17 items with low information were dropped. Post-hoc simulation using computerized adaptive test (CAT) modeling selected the most commonly used items (n=9 of 21 items) that represented the latent trait well (r=0.94) and differentiated NC from MCI participants (F(1,146)=8.9, p=0.003). CONCLUSION: Item response theory and computerized adaptive test modeling identified nine reliable SCD items. This pilot study is a first step toward refining SCD assessment in older adults. Replication of these findings and validation with Alzheimer's disease biomarkers will be an important next step for the creation of a SCD screener. PMID- 26878035 TI - Computer mouse movement patterns: A potential marker of mild cognitive impairment. AB - INTRODUCTION: Subtle changes in cognitively demanding activities occur in MCI but are difficult to assess with conventional methods. In an exploratory study, we examined whether patterns of computer mouse movements obtained from routine home computer use discriminated between older adults with and without MCI. METHODS: Participants were 42 cognitively intact and 20 older adults with MCI enrolled in a longitudinal study of in-home monitoring technologies. Mouse pointer movement variables were computed during one week of routine home computer use using algorithms that identified and characterized mouse movements within each computer use session. RESULTS: MCI was associated with making significantly fewer total mouse moves (p<.01), and making mouse movements that were more variable, less efficient, and with longer pauses between movements (p<.05). Mouse movement measures were significantly associated with several cognitive domains (p's<.01 .05). DISCUSSION: Remotely monitored computer mouse movement patterns are a potential early marker of real-world cognitive changes in MCI. PMID- 26878036 TI - Adenomas involving the extrahepatic biliary tree are rare but have an aggressive clinical course. AB - Biliary adenomas that are usually found in surgically removed gallbladders are rare, but can also occur in the extrahepatic biliary tree. We present a case series of extrahepatic bile duct adenomas at our institution, along with a review of the literature. All three patients with extrahepatic biliary adenomas (two in the common bile ducts, one in the hepatic duct) were female with a mean age of 74 years. On initial presentation, none of the patients had obstructive jaundice but two of the three patients had symptoms of biliary origin. Case 1 is an 85-year old woman with an incidental biliary dilation seen on chest imaging; endoscopic ultrasound revealed a sessile adenomatous polyp in the distal bile duct. The patient refused surgery and presented with occlusive biliary stricture and jaundice 5 months after initial presentation, with cytology confirming malignant progression. Case 2 is a 78-year-old woman with a history of primary sclerosing cholangitis and who presented with cholangitis, and Gram-negative sepsis. A polypoid lesion was seen on imaging in the common hepatic duct and direct cholangioscopy with biopsies confirmed the presence of adenoma with high grade dysplasia. The patient underwent successful total bile duct resection and hepaticojejunostomy but represented 1 year later with diffuse metastatic disease to the bone, liver, and peritoneum. Case 3 is a 61-year-old woman who presented with symptoms suggestive of gallbladder pathology and was found to have a polypoid bile duct lesion on intraoperative cholangiogram. Endoscopic retrograde cholangioscopy showed an adenomatous polyp with high grade dysplasia involving the distal common bile duct. The patient underwent distal bile duct resection with choledochojejunostomy but presented with jaundice 4 years after surgery. She was found to have adenocarcinoma involving the small bowel in the Roux limb of jejunum and transverse colon. All three patients in our series presented with interval gastrointestinal malignancy and we therefore recommend aggressive surgical intervention and close postoperative surveillance when diagnosis of extrahepatic bile duct adenoma is made. PMID- 26878038 TI - Implementing quality improvement programs for colonoscopy: the emerging need for an international, standardized, multidisciplinary approach. PMID- 26878037 TI - Barriers and facilitators to implementing continuous quality improvement programs in colonoscopy services: a mixed methods systematic review. AB - BACKGROUND AND AIM: Continuous quality improvement (CQI) programs may result in quality of care and outcome improvement. However, the implementation of such programs has proven to be very challenging. This mixed methods systematic review identifies barriers and facilitators pertaining to the implementation of CQI programs in colonoscopy services and how they relate to endoscopists, nurses, managers, and patients. METHODS: We developed a search strategy adapted to 15 databases. Studies had to report on the implementation of a CQI intervention and identified barriers or facilitators relating to any of the four groups of actors directly concerned by the provision of colonoscopies. The quality of the selected studies was assessed and findings were extracted, categorized, and synthesized using a generic extraction grid customized through an iterative process. RESULTS: We extracted 99 findings from the 15 selected publications. Although involving all actors is the most cited factor, the literature mainly focuses on the facilitators and barriers associated with the endoscopists' perspective. The most reported facilitators to CQI implementation are perception of feasibility, adoption of a formative approach, training and education, confidentiality, and assessing a limited number of quality indicators. Receptive attitudes, a sense of ownership and perceptions of positive impacts also facilitate the implementation. Finally, an organizational environment conducive to quality improvement has to be inclusive of all user groups, explicitly supportive, and provide appropriate resources. CONCLUSION: Our findings corroborate the current models of adoption of innovations. However, a significant knowledge gap remains with respect to barriers and facilitators pertaining to nurses, patients, and managers. PMID- 26878039 TI - Emerging techniques and efficacy of endoscopic esophageal reconstruction and lumen restoration for complete esophageal obstruction. AB - BACKGROUND AND STUDY AIMS: Complete esophageal obstruction (CEO) is a rare occurrence characterized by progressive esophageal stricture, which eventually causes lumen obliteration. With recent advances in flexible endoscopy, various innovative techniques exist for restoring luminal continuity. The primary aim of this study was to assess the efficacy and safety of patients undergoing combined antegrade-retrograde endoscopic dilation for CEO at our institution. The secondary aim was to review and highlight emerging techniques, outcomes, and adverse events after endoscopic treatment of CEO. PATIENTS AND METHODS: Our electronic endoscopy database was retrospectively reviewed to identify patients who underwent combined antegrade and retrograde endoscopy for CEO. Patient and procedural data collected included gender, age, technical success, pre- and post dysphagia scores, and adverse events. RESULTS: Six patients (67 % male, mean age 71.6 years [range 63 - 80]) underwent technically successful esophageal reconstruction with combined antegrade-retrograde endoscopy. All patients noted improvement in dysphagia with mean pre-procedure dysphagia score of 4 reduced to 1.33 (range 0 - 3) post-procedure. There were no adverse events and mean follow up time was 17.3 months (range 3 - 48). CONCLUSIONS: Combined antegrade and retrograde endoscopic therapy for CEO is feasible and safe. We present our experience with endoscopic management of complete esophageal obstruction, and highlight emerging techniques, outcomes and adverse events related to this minimally invasive modality. PMID- 26878041 TI - How to measure endoscopy unit performance: some metrics for dummies. PMID- 26878040 TI - Evaluation of interventional endoscopy unit efficiency metrics at a tertiary academic medical center. AB - BACKGROUND AND STUDY AIMS: There is an increasing demand for interventional endoscopic services and the need to develop efficient endoscopic units. The aim of this study was to analyze performance data and define metrics to improve efficiency in a single academic interventional endoscopy center. ] PATIENTS AND METHODS: The prospective operations performance data (6-month period) of our interventional endoscopy unit (EU) was analyzed. First-case start time (FIRST) delay was defined as any time the first patient of the day entered the endoscopy room after the scheduled time. Non-endoscopy time (NET) and total time (TT) were defined as non-procedural and total time elapsed in the EU, respectively. Time interval between successive patients (TISP) was defined as the time from one patient departure from the room until the time of arrival of the next patient in the room. RESULTS: A total of 1421 patients underwent 1635 endoscopic procedures. FIRST was delayed (54.2 % cases) by 13.6 min (range 1 - 53), but started within 15 min of the scheduled time in 85 % of the cases. NET accounted for 9.1 hours (67.2 %) of 13.5 hours TT/day. TISP (37.1 min, range 5 - 125) comprised 54.2 % of the NET, and was delayed (> 30 min) in 49.8 % of cases. "Patient flow" processes (registration, admission, transportation, scheduling) accounted for 50.1 % of TISP delays. CONCLUSIONS: Delays in NET, specifically TISP, rather than FIRST, were identified as a cause for decreased efficiency. "Patient flow" processes were the main reasons for delays in TISP. This study identifies potential process measures that can be used as benchmarks to improve efficiency in the EU. PMID- 26878042 TI - Overtube-assisted enteroscopy and capsule endoscopy for the diagnosis of small bowel polyps and tumors: a systematic review and meta-analysis. AB - BACKGROUND AND STUDY AIMS: Several studies have evaluated the utility of double balloon enteroscopy (DBE) and capsule endoscopy (CE) for patients with small bowel disease showing inconsistent results. The aim of this study was to determine the sensitivity and specificity of overtube-assisted enteroscopy (OAE) as well as the diagnostic concordance between OAE and CE for small-bowel polyps and tumors. PATIENTS AND METHODS: We conducted a systematic review and meta analysis of studies in which the results of OAE were compared with the results of CE for the evaluation of small-bowel polyps and tumors. When data for surgically resected lesions were available, the histopathological results of OAE and surgical specimens were compared. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for the diagnosis of small-bowel polyps and tumors were analyzed. Secondarily, the rates of diagnostic concordance and discordance between OAE and CE were calculated. RESULTS: There were 15 full length studies with a total of 821 patients that met the inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were as follows: 0.89 (95 % confidence interval [CI] 0.84 - 0.93), with heterogeneity chi(2) = 41.23 (P = 0.0002) and inconsistency (I (2)) = 66.0 %; 0.97 (95 %CI 0.95 - 0.98), with heterogeneity chi(2) = 45.27 (P = 0.07) and inconsistency (I (2)) = 69.1 %; 16.61 (95 %CI 3.74 - 73.82), with heterogeneity Cochrane's Q = 225.19 (P < 0.01) and inconsistency (I (2)) = 93.8 %; and 0.14 (95 %CI 0.05 - 0.35), with heterogeneity Cochrane's Q = 81.01 (P < .01) and inconsistency (I (2)) = 82.7 %, respectively. A summary receiver operating characteristic curve (SROC) curve was constructed, and the area under the curve (AUC) was 0.97. CONCLUSION: OAE is an accurate test for the detection of small-bowel polyps and tumors. OAE and CE have a high diagnostic concordance rate for small-bowel polyps and tumors. This study was registered in the PROSPERO international database (www.crd.york.ac.uk/prospero/) with the study number CRD42015016000. PMID- 26878044 TI - The loop-forming method as a useful technique to rotate the endoscopic insertion tube shaft. AB - BACKGROUND AND STUDY AIMS: Gastroenterological endoscopists are instructed to bring the target to the 6-o'clock position when they take a biopsy specimen, use a snare, or cut a target organ. This action is performed primarily by rotating the shaft of the endoscopic insertion tube, which can be difficult in some situations when existing endoscopic methods are used. We previously described a method for optimal rotation of the endoscopic insertion tube shaft, called the loop-forming method (LFM). The present study aimed to validate this procedure and confirm the usefulness of the LFM for leftward rotation of the shaft. PARTICIPANTS AND METHODS: The LFM was specifically taught to 28 gastroenterological endoscopists, and the angle of rotation was measured before and after they received instruction in this method. RESULTS: The LFM significantly increased the average angle of leftward rotation from 266 degrees to 327 degrees . Moreover, whereas the instrument channel inlet tended to move away from the right hand of an operator using a conventional endoscopy method, it remained closely accessible to the right hand of an examiner using the LFM. CONCLUSIONS: The LFM has the potential to make endoscopic procedures easier and safer. PMID- 26878043 TI - Colonoscopy detects significantly more flat adenomas than 3-tesla magnetic resonance colonography: a pilot trial. AB - BACKGROUND AND STUDY AIMS: Colorectal cancer (CRC) is one of the most common cancers worldwide, and several efforts have been made to reduce its occurrence or severity. Although colonoscopy is considered the gold standard in CRC prevention, it has its disadvantages: missed lesions, bleeding, and perforation. Furthermore, a high number of patients undergo this procedure even though no polyps are detected. Therefore, an initial screening examination may be warranted. Our aim was to compare the adenoma detection rate of magnetic resonance colonography (MRC) with that of optical colonoscopy. PATIENTS AND METHODS: A total of 25 patients with an intermediate risk for CRC (17 men, 8 women; mean age 57.6, standard deviation 11) underwent MRC with a 3.0-tesla magnet, followed by colonoscopy. The endoscopist was initially blinded to the results of MRC and unblinded immediately after examining the distal rectum. Following endoscopic excision, the size, anatomical localization, and appearance of all polyps were described according to the Paris classification. RESULTS: A total of 93 lesions were detected during colonoscopy. These included a malignant infiltration of the transverse colon due to gastric cancer in 1 patient, 28 adenomas in 10 patients, 19 hyperplastic polyps in 9 patients, and 45 non-neoplastic lesions. In 5 patients, no lesion was detected. MRC detected significantly fewer lesions: 1 adenoma (P = 0.001) and 1 hyperplastic polyp (P = 0.004). The malignant infiltration was seen with both modalities. Of the 28 adenomas, 23 (82 %) were 5 mm or smaller; only 4 adenomas 10 mm or larger (14 %) were detected. CONCLUSION: MRC does not detect adenomas sufficiently independently of the location of the lesion. Even advanced lesions were missed. Therefore, colonoscopy should still be considered the current gold standard, even for diagnostic purposes. PMID- 26878045 TI - International multicenter comparative trial of transluminal EUS-guided biliary drainage via hepatogastrostomy vs. choledochoduodenostomy approaches. AB - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) can be performed entirely transgastrically (hepatogastrostomy/EUS-HG) or transduodenally (choledochoduodenostomy/EUS-CDS). It is unknown how both techniques compare. The aims of this study were to compare efficacy and safety of both techniques and identify predictors of adverse events. PATIENTS AND METHODS: Consecutive jaundiced patients with distal malignant biliary obstruction who underwent EUS-BD at multiple international centers were included. Technical/clinical success, adverse events, stent complications, and survival were assessed. RESULTS: A total of 121 patients underwent EUS-BD (CDS 60, HG 61). Technical success was achieved in 112 (92.56 %) patients (EUS-CDS 93.3 %, EUS-HG 91.8 %, P = 0.75). Clinical success was attained in 85.5 % of patients who underwent EUS-CDS group as compared to 82.1 % of patients who underwent EUS-HG (P = 0.64). Adverse events occurred more commonly in the EUS-HG group (19.67 % vs. 13.3 %, P = 0.37). Both plastic stenting (OR 4.95, 95 %CI 1.41 - 17.38, P = 0.01) and use of non-coaxial electrocautery (OR 3.95, 95 %CI 1.16 - 13.40, P = 0.03) were independently associated with adverse events. Length of hospital stay was significantly shorter in the CDS group (5.6 days vs. 12.7 days, P < 0.001). Mean follow-up duration was 151 +/- 159 days. The 1-year stent patency probability was greater in the EUS-CDS group [0.98 (95 %CI 0.76 - 0.96) vs 0.60 (95 %CI 0.35 - 0.78)] but overall patency was not significantly different. There was no difference in median survival times between the groups (P = 0.36) CONCLUSIONS: Both EUS-CDS and EUS-HG are effective and safe techniques for the treatment of distal biliary obstruction after failed ERCP. However, CDS is associated with shorter hospital stay, improved stent patency, and fewer procedure- and stent related complications. Metallic stents should be placed whenever feasible and non coaxial electrocautery should be avoided when possible as plastic stenting and non-coaxial electrocautery were independently associated with occurrence of adverse events. PMID- 26878046 TI - Polypectomy skills of gastroenterology fellows: can we improve them? AB - BACKGROUND AND AIMS: Currently, most training programs for gastroenterology (GI) fellows lack systematic training in polypectomy. Systematic education and direct feedback with the direct observational polypectomy skills (DOPyS) method is a simple and inexpensive way to train GI fellows in practical endoscopy. Our primary aim was to evaluate whether a lecture-based training course could improve the polypectomy skills of GI fellows. As a secondary aim, the interobserver agreement among the three assessors was evaluated. PARTICIPANTS AND METHODS: We invited GI fellows to record five polypectomies, after which they attended a training course consisting of three lectures on polyps and polypectomy methods given by expert endoscopists. After training, the fellows recorded five polypectomies again. All videos were blindly assessed by three expert endoscopists, who used the DOPyS method. RESULTS: Eight GI fellows participated in this study. There was no significant difference in the median overall competency scores before and after training; before training, 25 % (10/40) of the polypectomies were scored as "pass," compared with 37.5 % (15/40) after training (P = 0.56). The interobserver agreement among the experts was fair (intraclass correlation coefficient [ICC] 0.34, 95 % confidence interval [CI] 0.14 - 0.52). CONCLUSIONS: Our lecture-based training course did not result in an improvement in overall competency scores for the polypectomy skills of GI fellows. Besides, the overall quality of the polypectomy techniques of the fellows was considered low. To optimize polypectomy training and competency, we believe that direct feedback in the endoscopy suite and hands-on training by dedicated teachers are essential. PMID- 26878047 TI - A novel wide viewing endoscope for upper gastrointestinal screening: a pilot study. AB - The feasibility of full-spectrum endoscopy (FUSE) esophagogastroduodenoscopy (EGD), providing a 245-degree field of view with double imagers on the front and left side of the endoscope was evaluated. Twenty-one healthy individuals (15 male, median age, 35 years) underwent upper gastrointestinal screening using FUSE EGD. The primary end point was the rate of successful visualization of Vater's papilla. Secondary end points were visualization of the squamo-columnar junction (SCJ) and the anal side of the pyloric ring, and the endoscopists' subjective evaluation of usability based on maneuverability and imaging of FUSE-EGD. The mean procedure time was 6.5 min, with a median of 91 images captured. The rate of successful visualization of Vater's papilla was 90 % (19/21). The whole circumference of the SCJ was observed with two video monitors in all cases. The anterior anal side of the pyloric ring was observed in 29 % (6/21) of cases. However, the general impression of the usability of FUSE-EGD was that it was rather inferior to that of a standard front viewing endoscope. Although the usability requires further modification, FUSE-EGD provided excellent results for imaging Vater's papilla and the SCJ. PMID- 26878048 TI - Performing forward-viewing endoscopy at time of pancreaticobiliary EUS and ERCP may detect additional upper gastrointestinal lesions. AB - BACKGROUND AND STUDY AIMS: It is unknown whether significant incidental upper gastrointestinal lesions are missed when using non-forward-viewing endoscopes without completing a forward-viewing exam in linear endoscopic ultrasound (EUS) or endoscopic retrograde cholangiopancreatography (ERCP) exams. We evaluated whether significant upper GI lesions are missed during EUS and ERCP when upper endoscopy is not performed routinely with a gastroscope. PATIENTS AND METHODS: A retrospective analysis was performed in which an EGD with a forward-viewing gastroscope was performed after using a non-forward-viewing endoscope (linear echoendoscope, duodenoscope, or both) during a single procedure. Upper gastrointestinal tract findings were recorded separately for each procedure. Significant lesions found with a forward-viewing gastroscope were defined as findings that led to a change in the patient's medication regimen, additional endoscopic surveillance/interventions, or the need for other imaging studies. RESULTS: A total of 168 patients were evaluated. In 83 patients, a linear echoendoscope was used, in 52 patients a duodenoscope was used, and in 33 patients both devices were used. Clinically significant additional lesions diagnosed with a gastroscope but missed by a non-forward-viewing endoscope were found in 30 /168 patients (18 %). EGD after linear EUS resulted in additional lesion findings in 17 /83 patients (20.5 %, chi(2) = 13.385, P = 0.00025). EGD after use of a duodenoscope resulted in additional lesions findings in 10 /52 patients (19.2 %, chi(2) = 9.987, P = 0.00157). EGD after the use of both a linear echoendoscope and a duodenoscope resulted in additional lesions findings in 3/33 patients (9 %, chi(2) = 3.219, P = 0.07). CONCLUSION: Non forward-viewing endoscopes miss a significant amount of incidental upper gastrointestinal lesions during pancreaticobiliary endoscopy. Performing an EGD with a gastroscope at the time of linear EUS or ERCP can lead to increased yield of upper gastrointestinal lesions. PMID- 26878049 TI - Endoscopic investigation in non-iron deficiency anemia: a cost to the health system without patient benefit. AB - BACKGROUND AND AIMS: The indication for endoscopy to investigate anemia of causes other than iron deficiency is not clear. Increasing numbers of endoscopic procedures for anemia raises concerns about costs to the health system, waiting times, and patient safety. The primary aim of this study was to determine the diagnostic yield of endoscopy in patients referred to undergo investigation for anemia. Secondary aims were to identify additional factors enabling the risk stratification of those likely to benefit from endoscopic investigation, and to undertake a cost analysis of performing endoscopy in this group of patients. METHODS: We performed a retrospective review of endoscopy referrals for the investigation of anemia over a 12-month period at a single center. The patients were divided into three groups: those who had true iron deficiency anemia (IDA), tissue iron deficiency without anemia (TIDWA), or anemia of other cause (AOC). Outcome measures included finding a lesion responsible for the anemia and a significant change of management as a result of endoscopy. A costing analysis was performed with an activity-based costing method. RESULTS: We identified 283 patients who underwent endoscopy to investigate anemia. A likely cause of anemia was found in 31 of 150 patients with IDA (21 %) and 0 patients in the other categories (P < 0.001). A change of management was observed in 35 patients with IDA (23 %), 1 of 14 patients with TIDWA (7.14 %), and 8 of 119 patients with AOC (6.7 %) (P < 0.001). The cost of a single colonoscopy or gastroscopy was approximated to be $ 2209. CONCLUSIONS: Endoscopic investigation for non-IDA comes at a significant cost to our institution, equating to a minimum of $ 293 797 per annum in extra costs, and does not result in a change of management in the majority of patients. No additional factors could be established to identify patients who might be more likely to benefit from endoscopic investigation. The endoscopic investigation of non-IDA should be minimized. PMID- 26878050 TI - Cap-assisted retrograde single-balloon enteroscopy results in high terminal ileal intubation rate. AB - BACKGROUND AND STUDY AIMS: Retrograde single-balloon enteroscopy (RSBE) facilitates evaluation of the distal small bowel and provision of appropriate therapy when necessary. Intubation of the terminal ileum (TI) is a major rate limiting step, with failure rates as high as 30 %. Cap-assisted endoscopy has proven beneficial in other aspects of endoscopy. We have noticed that it similarly aids in TI intubation during RSBE by facilitating opening of the ileocecal valve (ICV). The primary aim of this study was to measure the TI intubation rate using cap-assisted RSBE. Other procedural details and outcomes were also measured. PATIENTS AND METHODS: A total of 36 consecutive RSBEs performed between July 2011 and May 2014 at the Medical University of South Carolina were retrospectively reviewed. All procedures were performed or supervised by our center's small bowel endoscopist (ASB). Outcomes measured included TI intubation rate, procedure time, depth of maximal insertion (DMI), diagnostic yield (DY), therapeutic yield (TY), and complications. RESULTS: The TI intubation rate was 97 % (35 /36). The one failure was due to stool completely obscuring the cecum. Median procedure time was 54 minutes, with a mean DMI of 68 cm beyond the ICV. The technical success rate was 86 %, whereas DY and TY were 61 % and 25 %, respectively. There were no complications. The study was limited in that it involved a single endoscopist at a single center. CONCLUSIONS: Cap assisted RSBE results in a high TI intubation rate, without compromise to safety or procedural yield. PMID- 26878052 TI - What can we learn from publishing endoscopy trial protocols? PMID- 26878051 TI - The ADENOMA Study. Accuracy of Detection using Endocuff VisionTM Optimization of Mucosal Abnormalities: study protocol for randomized controlled trial. AB - BACKGROUND: Colonoscopy is the gold standard investigation for the diagnosis of bowel pathology and colorectal cancer screening. Adenoma detection rate is a marker of high quality colonoscopy and a high adenoma detection rate is associated with a lower incidence of interval cancers. Several technological advancements have been explored to improve adenoma detection rate. A new device called Endocuff VisionTM has been shown to improve adenoma detection rate in pilot studies. METHODS/DESIGN: This is a prospective, multicenter, randomized controlled trial comparing the adenoma detection rate in patients undergoing Endocuff VisionTM-assisted colonoscopy with standard colonoscopy. All patients above 18 years of age referred for screening, surveillance, or diagnostic colonoscopy who are able to consent are invited to the study. Patients with absolute contraindications to colonoscopy, large bowel obstruction or pseudo obstruction, colon cancer or polyposis syndromes, colonic strictures, severe diverticular segments, active colitis, anticoagulant therapy, or pregnancy are excluded. Patients are randomized according to site, age, sex, and bowel cancer screening status to receive Endocuff VisionTM-assisted colonoscopy or standard colonoscopy on the day of procedure. Baseline data, colonoscopy, and polyp data including histology are collected. Nurse assessment of patient comfort and patient comfort questionnaires are completed post procedure. Patients are followed up at 21 days and complete a patient experience questionnaire. This study will take place across seven NHS Hospital Trusts: one in London and six within the Northern Region Endoscopy Group. A maximum of 10 colonoscopists per site will recruit a total of 1772 patients, with a maximum of four bowel screening colonoscopists permitted per site. DISCUSSION: This is the first trial to evaluate the adenoma detection rate of Endocuff VisionTM in all screening, surveillance, and diagnostic patient groups. This timely study will guide clinicians as to the role of Endocuff VisionTM in routine colonoscopy. STUDY REGISTRATION: ISRCTN11821044. PMID- 26878054 TI - Endoscopic sleeve gastroplasty with 1-year follow-up: factors predictive of success. AB - BACKGROUND AND STUDY AIMS: Bariatric endoscopy has emerged as an aid in the nonsurgical treatment of obesity. The objective of this study is to critically provide the results and follow-up of endoscopic sleeve gastroplasty 1 year after the procedure. PATIENTS AND METHODS: Prospective single-center follow-up study of 25 patients (5 men, 20 women) who underwent flexible endoscopic suturing for endoluminal gastric volume reduction. A multidisciplinary team provided post procedure care. Patient outcomes were recorded at 1 year after the procedure. Linear regression analysis was done to evaluate the variables associated with best results at 1 year of follow-up. RESULTS: Mean body mass index (BMI) was 38.5 +/- 4.6 kg/m(2) (range 30 - 47) and mean age 44.5 +/- 8.2 years (range 29 - 60). At 1 year, 22 patients continued with the follow-up (2 dropped out at 6 months and 1 at 3 months). There were no major intra-procedural, early, or delayed adverse events. Mean BMI loss was 7.3 +/- 4.2 kg/m(2), and mean percentage of total body weight loss was 18.7 +/- 10.7 at 1 year. In the linear regression analysis, adjusted by initial BMI, variables associated with %TBWL involved the frequency of nutritional (beta = 0.563, P = 0.014) and psychological contacts (beta = 0.727, P = 0.025). The number of nutritional and psychological contacts were predictive of good weight loss results. CONCLUSIONS: Endoscopic sleeve gastroplasty is a feasible, reproducible, and effective procedure to treat obesity. Nutritional and psychological interaction are predictive of success. PMID- 26878053 TI - Does magnetically assisted capsule endoscopy improve small bowel capsule endoscopy completion rate? A randomised controlled trial. AB - BACKGROUND AND STUDY AIMS: Delayed gastric emptying is a significant factor in incomplete small bowel capsule examinations. Gastric transit could be hastened by external magnetic control of the capsule. We studied the feasibility of this approach to improve capsule endoscopy completion rates. PATIENTS AND METHODS: Prospective, single-center, randomized controlled trial involving 122 patients attending for small bowel capsule endoscopy using MiroCam Navi. Patients were randomized to either the control group (mobilisation for 30 minutes after capsule ingestion, followed by intramuscular metoclopramide 10 mg if the capsule failed to enter the small bowel) or the intervention group (1000 mL of water prior to capsule ingestion, followed by positional change and magnetic steering). Outcome measures were capsule endoscopy completion rate, gastric clarity and distention, relationship of body habitus to capsule endoscopy completion rate (CECR), and patient comfort scores. RESULTS: 122 patients were recruited (61 each to the control and intervention groups: mean age 49 years [range 21 - 85], 61 females). There was no significant difference in CECR between the two groups (P = 0.39). Time to first pyloric image was significantly shorter in the intervention group (P = 0.03) but there was no difference in gastric transit times (P = 0.12), suggesting that magnetic control hastens capsular transit to the gastric antrum but does not influence duodenal passage. Gastric clarity and distention were significantly better in the intervention group (P < 0.0001 and P < 0.0001 respectively). CONCLUSIONS: Magnetic steering of a small bowel capsule is unable to overcome pyloric contractions to enhance gastric emptying and improve capsule endoscope completion rate. Excellent mucosal visualisation within the gastric cavity suggests this technique could be harnessed for capsule examination of the stomach. PMID- 26878055 TI - Video capsule endoscopy completion and total transit times are similar with oral or endoscopic delivery. AB - BACKGROUND AND STUDY AIMS: Video capsule endoscopy (VCE) is limited by incomplete procedures. There are also contraindications to the standard ingestion of the capsule that require endoscopic placement. Our aim was to compare the study completion rate of VCE after oral ingestion and endoscopic deployment. PATIENTS AND METHODS: We performed a review of all VCE from April 2010 through March 2013. Inpatient and outpatient cohorts grouped by the method of capsule delivery were formed and compared. Multivariable logistic regression modeling was utilized adjusting for variables with a P value <= 0.1 in group comparisons. Log-rank analysis was used to compare transit times. RESULTS: A total of 687 VCE were performed, including 316 inpatient (36 endoscopic deployment, 280 oral ingestion) and 371 outpatient (20 endoscopic deployment, 351 oral ingestion). For VCE on hospitalized patients, the completion rates were similar after endoscopic deployment and oral ingestion (72 % vs 73 %, P = 0.94). The completion rates were also similar for ambulatory patients (90 % vs 87 %, P = 0.69). There remained no difference after multivariable modeling for inpatients (P = 0.71) and outpatients (P = 0.46). Total transit times were not significantly different. CONCLUSIONS: VCE completion rates and total transit times are similar after oral or endoscopic deployment for both hospitalized and ambulatory patients. Endoscopic placement is effective in patients with contraindications to standard oral ingestion, but should otherwise be avoided to limit unnecessary procedural risks and costs. PMID- 26878056 TI - Endoscopic band ligation for colonic diverticular bleeding: possibility of standardization. AB - BACKGROUND AND AIMS: Endoscopic band ligation (EBL) has been used to achieve hemostasis in patients with colonic diverticular bleeding. The safety and effectiveness of EBL when performed by non-expert endoscopists have not been sufficiently verified. This study aimed to elucidate the feasibility of the EBL technique when performed by non-expert endoscopists and of considering EBL as a standard treatment for colonic diverticular bleeding. PATIENTS AND METHODS: A retrospective cohort study was conducted in a tertiary referral center in Tokyo, Japan, between June 2009 and October 2014. A total of 95 patients treated with EBL were included in the study and were divided into two groups according to whether they had been treated by expert or non-expert endoscopists. Comorbidities, medications, shock index, hemoglobin level on admission, location of the bleeding diverticula, rate of bowel preparation, procedure time, and EBL associated adverse events were evaluated in each group. Multivariate linear regression analyses were used to investigate factors related to EBL procedure time, which is the time elapsed between marking the site of bleeding with hemoclips and completion of the band release. RESULTS: A total of 47 (49.5 %) procedures were performed by expert endoscopists. In a bivariate analysis, the median EBL procedure times in the expert and non-expert groups were 15 minutes (range 4 - 45) and 11 minutes (range 4 - 36), respectively (P = 0.03). When a multivariate linear regression model was used, EBL for right-sided diverticula was the factor most significantly affecting EBL procedure time. No adverse events were encountered. CONCLUSION: EBL can be safely and effectively performed by non expert endoscopists. A right-sided location of diverticula was the factor most significantly affecting EBL procedure time. PMID- 26878057 TI - Testosterone Modulates Altered Prefrontal Control of Emotional Actions in Psychopathic Offenders(1,2,3). AB - Psychopathic individuals are notorious for their controlled goal-directed aggressive behavior. Yet, during social challenges, they often show uncontrolled emotional behavior. Healthy individuals can control their social emotional behavior through anterior prefrontal cortex (aPFC) downregulation of neural activity in the amygdala, with testosterone modulating aPFC-amygdala coupling. This study tests whether individual differences in this neuroendocrine system relate to the paradoxical lack of emotional control observed in human psychopathic offenders. Emotional control was operationalized with an fMRI adapted approach-avoidance task requiring rule-driven control over rapid emotional responses. Fifteen psychopathic offenders and 19 matched healthy control subjects made approaching and avoiding movements in response to emotional faces. Control of social emotional behavior was required during affect incongruent trials, when participants had to override affect-congruent, automatic action tendencies and select the opposite response. Psychopathic offenders showed less control-related aPFC activity and aPFC-amygdala coupling during trials requiring control of emotional actions, when compared with healthy control subjects. This pattern was particularly pronounced in psychopathic individuals with high endogenous testosterone levels. These findings suggest that reduced prefrontal coordination underlies reduced behavioral control in psychopathic offenders during emotionally provoking situations. Even though the modest sample size warrants replication, the modulatory role of endogenous testosterone on the aPFC-amygdala circuit suggests a neurobiological substrate of individual differences that is relevant for the advancement of treatment and the reduction of recidivism. PMID- 26878058 TI - Chemical Genomics-Based Antifungal Drug Discovery: Targeting Glycosylphosphatidylinositol (GPI) Precursor Biosynthesis. AB - Steadily increasing antifungal drug resistance and persistent high rates of fungal-associated mortality highlight the dire need for the development of novel antifungals. Characterization of inhibitors of one enzyme in the GPI anchor pathway, Gwt1, has generated interest in the exploration of targets in this pathway for further study. Utilizing a chemical genomics-based screening platform referred to as the Candida albicans fitness test (CaFT), we have identified novel inhibitors of Gwt1 and a second enzyme in the glycosylphosphatidylinositol (GPI) cell wall anchor pathway, Mcd4. We further validate these targets using the model fungal organism Saccharomyces cerevisiae and demonstrate the utility of using the facile toolbox that has been compiled in this species to further explore target specific biology. Using these compounds as probes, we demonstrate that inhibition of Mcd4 as well as Gwt1 blocks the growth of a broad spectrum of fungal pathogens and exposes key elicitors of pathogen recognition. Interestingly, a strong chemical synergy is also observed by combining Gwt1 and Mcd4 inhibitors, mirroring the demonstrated synthetic lethality of combining conditional mutants of GWT1 and MCD4. We further demonstrate that the Mcd4 inhibitor M720 is efficacious in a murine infection model of systemic candidiasis. Our results establish Mcd4 as a promising antifungal target and confirm the GPI cell wall anchor synthesis pathway as a promising antifungal target area by demonstrating that effects of inhibiting it are more general than previously recognized. PMID- 26878059 TI - Biomimetic molecules lower catabolic expression and prevent chondroitin sulfate degradation in an osteoarthritic ex vivo model. AB - Aggrecan, the major proteoglycan in cartilage, serves to protect cartilage tissue from damage and degradation during the progression of osteoarthritis (OA). In cartilage extracellular matrix (ECM) aggrecan exists in an aggregate composed of several aggrecan molecules that bind to a single filament of hyaluronan. Each molecule of aggrecan is composed of a protein core and glycosaminoglycan sides chains, the latter of which provides cartilage with the ability to retain water and resist compressive loads. During the progression of OA, loss of aggrecan is considered to occur first, after which other cartilage matrix components become extremely susceptible to degradation. Proteolytic cleavage of the protein core of aggrecan by enzymes such as aggrecanases, prevent its binding to HA and lower cartilage mechanical strength. Here we present the use of HA-binding or collagen type II-binding molecules that functionally mimic aggrecan but lack known cleavage sites, protecting the molecule from proteolytic degradation. These molecules synthesized with chondroitin sulfate backbones conjugated to hyaluronan or collagen type II- binding peptides, are capable of diffusing through a cartilage explant and adhering to the ECM of this tissue. The objective of this study was to test the functional efficacy of these molecules in an ex vivo osteoarthritic model to discern the optimal molecule for further studies. Different variations of chondroitin sulfate conjugated to the binding peptides were diffused through aggrecan depleted explants and assessed for their ability to enhance compressive stiffness, prevent CS degradation, and modulate catabolic (MMP-13 and ADAMTS-5) and anabolic (aggrecan and collagen type II) gene expression. A pilot in vivo study assessed the ability to retain the molecule within the joint space of an osteoarthritic guinea pig model. The results indicate chondroitin sulfate conjugated to hyaluronan-binding peptides is able to significantly restore equilibrium modulus and prevent CS degradation. All molecules demonstrated the ability to lower catabolic gene expression in aggrecan depleted explants. In order to enhance biosynthesis and regeneration, the molecules need to be coupled with an external stimulant such as a growth factor. The chondroitin sulfate molecule synthesized with HA-binding peptides demonstrated adherence to cartilage tissue and retention up to 6 hours in an ambulatory joint. Further studies will monitor the in vivo residence time and ability of the molecules to act as a disease-modifying agent. PMID- 26878060 TI - A Turnstile Mechanism for the Controlled Growth of Biosynthetic Intermediates on Assembly Line Polyketide Synthases. AB - Vectorial polyketide biosynthesis on an assembly line polyketide synthase is the most distinctive property of this family of biological machines, while providing the key conceptual tool for the bioinformatic decoding of new antibiotic pathways. We now show that the action of the entire assembly line is synchronized by a previously unrecognized turnstile mechanism that prevents the ketosynthase domain of each module from being acylated by a new polyketide chain until the product of the prior catalytic cycle has been passed to the downstream module from the corresponding acyl carrier protein domain. The turnstile is closed by virtue of tight coupling to the signature decarboxylative condensation reaction catalyzed by the ketosynthase domain of each polyketide synthase module. Reopening of the turnstile is coupled to the eventual chain translocation step that vacates the module. At the maximal rate of substrate turnover, one would expect the chain release step to initiate a cascade of chain translocation events that sequentially migrate back upstream, thereby repriming each module and setting up the assembly line for the next round of polyketide chain elongation. PMID- 26878061 TI - Sea Spray Aerosol Structure and Composition Using Cryogenic Transmission Electron Microscopy. AB - The composition and surface properties of atmospheric aerosol particles largely control their impact on climate by affecting their ability to uptake water, react heterogeneously, and nucleate ice in clouds. However, in the vacuum of a conventional electron microscope, the native surface and internal structure often undergo physicochemical rearrangement resulting in surfaces that are quite different from their atmospheric configurations. Herein, we report the development of cryogenic transmission electron microscopy where laboratory generated sea spray aerosol particles are flash frozen in their native state with iterative and controlled thermal and/or pressure exposures and then probed by electron microscopy. This unique approach allows for the detection of not only mixed salts, but also soft materials including whole hydrated bacteria, diatoms, virus particles, marine vesicles, as well as gel networks within hydrated salt droplets-all of which will have distinct biological, chemical, and physical processes. We anticipate this method will open up a new avenue of analysis for aerosol particles, not only for ocean-derived aerosols, but for those produced from other sources where there is interest in the transfer of organic or biological species from the biosphere to the atmosphere. PMID- 26878062 TI - Identification of high-efficiency 3'GG gRNA motifs in indexed FASTA files with ngg2. AB - CRISPR/Cas9 is emerging as one of the most-used methods of genome modification in organisms ranging from bacteria to human cells. However, the efficiency of editing varies tremendously site-to-site. A recent report identified a novel motif, called the 3'GG motif, which substantially increases the efficiency of editing at all sites tested in C. elegans. Furthermore, they highlighted that previously published gRNAs with high editing efficiency also had this motif. I designed a python command-line tool, ngg2, to identify 3'GG gRNA sites from indexed FASTA files. As a proof-of-concept, I screened for these motifs in six model genomes: Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Mus musculus, and Homo sapiens. I also scanned the genomes of pig (Sus scrofa) and African elephant (Loxodonta africana) to demonstrate the utility in non-model organisms. I identified more than 60 million single match 3'GG motifs in these genomes. Greater than 61% of all protein coding genes in the reference genomes had at least one unique 3'GG gRNA site overlapping an exon. In particular, more than 96% of mouse and 93% of human protein coding genes have at least one unique, overlapping 3'GG gRNA. These identified sites can be used as a starting point in gRNA selection, and the ngg2 tool provides an important ability to identify 3'GG editing sites in any species with an available genome sequence. PMID- 26878064 TI - Zinc Ionophore (Clioquinol) Inhibition of Human ZIP1-Deficient Prostate Tumor Growth in the Mouse Ectopic Xenograft Model: A Zinc Approach for the Efficacious Treatment of Prostate Cancer. AB - Prostate cancer remains the second leading cause of cancer deaths in males. This is mainly due to the absence of an available efficacious chemotherapy despite decades of research in pursuit of effective treatment approaches. A plausible target for the treatment is the established clinical relationship that the zinc levels in the malignant cells are markedly decreased compared to the normal epithelium in virtually all cases of prostate cancer, and at all stages malignancy. The decrease in zinc results from the downregulation of the functional zinc uptake transporter, ZIP1; which occurs during early development of prostate malignancy. This is an essential requirement for the development of malignancy to prevent the cytotoxic/tumor-suppressor effects of increased zinc on the premalignant and malignant cells. Thus prostate cancer is a ZIP1-deficient malignancy. This relationship provides the basis for a treatment regimen that will facilitate the uptake and accumulation of zinc into the premalignant and malignant cells. In this report we employed a zinc ionophore (clioquinol) approach in the treatment of mice with human ZIP1-deficient prostate tumors (ectopic xenograft model). Clioquinol treatment resulted in 85%inhibition of tumor growth due to the cytotoxic effects of zinc. Coupled with additional results from earlier studies, the compelling evidence provides a plausible approach for the effective treatment of human prostate cancer; including primary site malignancy, hormone-resistant cancer, and metastasis. Additionally, this approach might be effective in preventing the development of malignancy in individuals suspected of presenting with early development of malignancy. Clinical trials are now required in leading to the potential for an efficacious zinc-treatment approach, which is urgently needed for the treatment of prostate cancer. PMID- 26878063 TI - Advances in Theory of Solid-State Nuclear Magnetic Resonance. AB - Recent advances in theory of solid state nuclear magnetic resonance (NMR) such as Floquet-Magnus expansion and Fer expansion, address alternative methods for solving a time-dependent linear differential equation which is a central problem in quantum physics in general and solid-state NMR in particular. The power and the salient features of these theoretical approaches that are helpful to describe the time evolution of the spin system at all times are presented. This review article presents a broad view of manipulations of spin systems in solid-state NMR, based on milestones theories including the average Hamiltonian theory and the Floquet theory, and the approaches currently developing such as the Floquet Magnus expansion and the Fer expansion. All these approaches provide procedures to control and describe the spin dynamics in solid-state NMR. Applications of these theoretical methods to stroboscopic and synchronized manipulations, non synchronized experiments, multiple incommensurated frequencies, magic-angle spinning samples, are illustrated. We also reviewed the propagators of these theories and discussed their convergences. Note that the FME is an extension of the popular Magnus Expansion and Average Hamiltonian Theory. It aims is to bridge the AHT to the Floquet Theorem but in a more concise and efficient formalism. Calculations can then be performed in a finite-dimensional Hilbert space instead of an infinite dimensional space within the so-called Floquet theory. We expected that the FME will provide means for more accurate and efficient spin dynamics simulation and for devising new RF pulse sequence. PMID- 26878065 TI - Reaction-Based Probes for Imaging Mobile Zinc in Live Cells and Tissues. AB - Chelatable, or mobile, forms of zinc play critical signaling roles in numerous biological processes. Elucidating the action of mobile Zn(II) in complex biological environments requires sensitive tools for visualizing, tracking, and manipulating Zn(II) ions. A large toolbox of synthetic photoinduced electron transfer (PET)-based fluorescent Zn(II) sensors are available, but the applicability of many of these probes is limited by poor zinc sensitivity and low dynamic ranges owing to proton interference. We present here a general approach for acetylating PET-based probes containing a variety of fluorophores and zinc binding units. The new sensors provide substantially improved zinc sensitivity and allow for incubation of live cells and tissue slices with nM probe concentrations, a significant improvement compared to the MUM concentrations that are typically required for a measurable fluorescence signal. Acetylation effectively reduces or completely quenches background fluorescence in the metal free sensor. Binding of Zn(II) selectively and quickly mediates hydrolytic cleavage of the acetyl groups, providing a large fluorescence response. An acetylated blue coumarin-based sensor was used to carry out detailed analyses of metal binding and metal-promoted acetyl hydrolysis. Acetylated benzoresorufin based red-emitting probes with different zinc-binding sites are effective for sensing Zn(II) ions in live cells when applied at low concentrations (~50-100 nM). We used green diacetylated Zinpyr1 (DA-ZP1) to image endogenous mobile Zn(II) in the molecular layer of mouse dorsal cochlear nucleus (DCN), confirming that acetylation is a suitable approach for preparing sensors that are highly specific and sensitive to mobile zinc in biological systems. PMID- 26878066 TI - Steroidogenesis and early response gene expression in MA-10 Leydig tumor cells following heterologous receptor down-regulation and cellular desensitization. AB - The Leydig tumor cell line, MA-10, expresses the luteinizing hormone receptor, a G protein-coupled receptor that, when activated with luteinizing hormone or chorionic gonadotropin (CG), stimulates cAMP production and subsequent steroidogenesis, notably progesterone. These cells also respond to epidermal growth factor (EGF) and phorbol esters with increased steroid biosynthesis. In order to probe the intracellular pathways along with heterologous receptor down regulation and cellular desensitization, cells were preincubated with EGF or phorbol esters and then challenged with CG, EGF, dibutryl-cyclic AMP, and a phorbol ester. Relative receptor numbers, steroid biosynthesis, and expression of the early response genes, JUNB and c-FOS, were measured. It was found that in all cases but one receptor down-regulation and decreased progesterone production were closely coupled under the conditions used; the exception involved preincubation of the cells with EGF followed by addition of CG where the CG-mediated stimulation of steroidogenesis was considerably lower than the level of receptor down-regulation. In a number of instances JUNB and c-FOS expression paralleled the decreases in receptor number and progesterone production, while in some cases these early response genes were affected little if at all by the changes in receptor number. This finding may indicate that even low levels of activated signaling kinases, e.g. protein kinase A, protein kinase C, or receptor tyrosine kinase, may suffice to yield good expression of JUNB and c-FOS, or it may suggest alternative pathways for regulating expression of these two early response genes. PMID- 26878068 TI - Real-Time Enrollment Dashboard For Multisite Clinical Trials. AB - OBJECTIVE: Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. MATERIALS AND METHODS: We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. RESULTS: The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. CONCLUSION: We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system. PMID- 26878069 TI - Generalization of Wei's urn design to unequal allocations in sequential clinical trials. AB - Wei's urn design was proposed in 1987 for subject randomization in trials comparing m >= 2 treatments with equal allocation. In this manuscript, two modified versions of Wei's urn design are presented to accommodate unequal allocations. First one uses a provisional allocation of [Formula: see text] to achieve the target allocation r1 : r2, and the second one uses equal allocation for r1 + r2 arms to achieve an unequal allocation r1 : r2 based on the concept Kaiser presented in his recent paper. The properties of these two designs are evaluated based on treatment imbalance and allocation predictability under different sample sizes and unequal allocation ratios. Simulations are performed to compare the two designs to other designs used for unequal allocations, include the complete randomization, permuted block randomization, block urn design, maximal procedure, and the mass weighted urn design. PMID- 26878067 TI - Imbalance in Resting State Functional Connectivity is Associated with Eating Behaviors and Adiposity in Children. PMID- 26878070 TI - Modulation of intrinsic brain activity by electroconvulsive therapy in major depression. AB - INTRODUCTION: One of the most effective interventions for intractable major depressive episodes is electroconvulsive therapy (ECT). Because ECT is also relatively fast-acting, longitudinal study of its neurobiological effects offers critical insight into the mechanisms underlying depression and antidepressant response. Here we assessed modulation of intrinsic brain activity in corticolimbic networks associated with ECT and clinical response. METHODS: We measured resting-state functional connectivity (RSFC) in patients with treatment resistant depression (n=30), using functional magnetic resonance imaging (fMRI) acquired before and after completing a treatment series with right-unilateral ECT. Using independent component analysis, we assessed changes in RSFC with 1) symptom improvement and 2) ECT regardless of treatment outcome in patients, with reference to healthy controls (n=33, also scanned twice). RESULTS: After ECT, consistent changes in RSFC within targeted depression-relevant functional networks were observed in the dorsal anterior cingulate (ACC), mediodorsal thalamus (mdTh), hippocampus, and right anterior temporal, medial parietal, and posterior cingulate cortex in all patients. In a separate analysis, changes in depressive symptoms were associated with RSFC changes in the dorsal ACC, mdTh, putamen, medial prefrontal, and lateral parietal cortex. RSFC of these regions did not change in healthy controls. CONCLUSIONS: Neuroplasticity underlying clinical change was in part separable from changes associated with the effects of ECT observed in all patients. However, both ECT and clinical change were associated with RSFC modulation in dorsal ACC, mdTh and hippocampus, which may indicate that these regions underlie the mechanisms of clinical outcome in ECT and may be effective targets for future neurostimulation therapies. PMID- 26878071 TI - PHARMACOKINETIC EXPOSURE AND VIROLOGIC RESPONSE IN HIV-1 INFECTED PREGNANT WOMEN TREATED WITH LOPINAVIR/RITONAVIR: AIDS CLINICAL TRIALS GROUP PROTOCOL A5153S: A SUBSTUDY TO A5150. AB - OBJECTIVE: We studied the pharmacokinetics and pharmacodynamics of boosted soft gel lopinavir/ritonavir to assess if the area under the plasma concentration versus time curve (AUC) is altered in pregnancy and whether changes in AUC impacted HIV-1 control. METHODS: We enrolled pregnant women >=13 years of age between 22 to 30 weeks gestation who expected to be on stable lopinavir/ritonavir for >=8 weeks pre-delivery and >=24 weeks post-delivery. Pharmacokinetic evaluations for lopinavir and ritonavir occurred at 36 weeks gestation and 6 and 24 weeks postpartum. RESULTS: Ten women underwent intensive pharmacokinetic evaluations for lopinavir and ritonavir at 36 weeks gestation and at 6 and 24 weeks postpartum. Estimated geometric mean (GM) AUC 0-6h (95% CI) for lopinavir were not significantly different at 26.5 (17.0, 41.4) and 41.9 (26.1, 67.5) mcg*hr/mL at 36 weeks gestation and 6 weeks postpartum, respectively (within subject GM ratio 0.60 (0.25, 1.43); p=0.19). At 36 weeks gestation, 5 of 10 women had viral load <50 copies/mL and at 6 weeks postpartum 5 of 9 had viral load <50 copies/mL. Nine of ten infants for whom data were available were HIV negative. CONCLUSION: Despite below target lopinavir levels (< 52 mcg*hr/mL except at 2 postpartum measurements), women maintained virologic control postpartum. Higher doses of lopinavir/ritonavir during pregnancy may not be necessary in all women. PMID- 26878072 TI - Chondrocyte Apoptosis in Rheumatoid Arthritis: Is Preventive Therapy Possible? PMID- 26878074 TI - Endothelial Progenitor Cells in Breast Cancer. AB - Recent evidences demonstrated the importance of bone marrow derived Endothelial Progenitor Cells (EPC), in the contribution to postnatal physiological and pathological neovascularization, and in tumor growth and angiogenesis. These cells are recruited undifferentiated, in response to systemic or chemoatractive signals, such as Vascular Endothelial Growth Factor (VEGF), they lodge in the growing or lesioned tissue and differentiate into endothelial cells in response to local stimuli and cell-cell interactions. The extent and the significance of the EPCs contribution for the growing of most tumors, including those of the breast, are still not fully defined. We analyzed the peripheral blood of breast cancer patients and found that they have circulating EPCs. We also found an association between expression of AC133+Kdr+ and VEGF plasma levels in these patients. Strategies to impair the mobilization and incorporation of EPCs into breast tumors may contribute to halt the growth of these tumors. PMID- 26878075 TI - Afterword: relevance and realities of anthropological critique of epidemiology. PMID- 26878073 TI - The HIV Cure Research Agenda: The Role of Mathematical Modelling and Cost Effectiveness Analysis. AB - The research agenda towards an HIV cure is building rapidly. In this article, we discuss the reasons for and methodological approach to using mathematical modeling and cost-effectiveness analysis in this agenda. We provide a brief description of the proof of concept for cure and the current directions of cure research. We then review the types of clinical economic evaluations, including cost analysis, cost-benefit analysis, and cost-effectiveness analysis. We describe the use of mathematical modeling and cost-effectiveness analysis early in the HIV epidemic as well as in the era of combination antiretroviral therapy. We then highlight the novel methodology of Value of Information analysis and its potential role in the planning of clinical trials. We close with recommendations for modeling and cost-effectiveness analysis in the HIV cure agenda. PMID- 26878076 TI - An unsupervised MVA method to compare specific regions in human breast tumor tissue samples using ToF-SIMS. AB - Imaging time-of-flight secondary ion mass spectrometry (ToF-SIMS) and principal component analysis (PCA) were used to investigate two sets of pre- and post chemotherapy human breast tumor tissue sections to characterize lipids associated with tumor metabolic flexibility and response to treatment. The micron spatial resolution imaging capability of ToF-SIMS provides a powerful approach to attain spatially-resolved molecular and cellular data from cancerous tissues not available with conventional imaging techniques. Three ca. 1 mm(2) areas per tissue section were analyzed by stitching together 200 MUm * 200 MUm raster area scans. A method to isolate and analyze specific tissue regions of interest by utilizing PCA of ToF-SIMS images is presented, which allowed separation of cellularized areas from stromal areas. These PCA-generated regions of interest were then used as masks to reconstruct representative spectra from specifically stromal or cellular regions. The advantage of this unsupervised selection method is a reduction in scatter in the spectral PCA results when compared to analyzing all tissue areas or analyzing areas highlighted by a pathologist. Utilizing this method, stromal and cellular regions of breast tissue biopsies taken pre- versus post-chemotherapy demonstrate chemical separation using negatively-charged ion species. In this sample set, the cellular regions were predominantly all cancer cells. Fatty acids (i.e. palmitic, oleic, and stearic), monoacylglycerols, diacylglycerols and vitamin E profiles were distinctively different between the pre- and post-therapy tissues. These results validate a new unsupervised method to isolate and interpret biochemically distinct regions in cancer tissues using imaging ToF-SIMS data. In addition, the method developed here can provide a framework to compare a variety of tissue samples using imaging ToF-SIMS, especially where there is section-to-section variability that makes it difficult to use a serial hematoxylin and eosin (H&E) stained section to direct the SIMS analysis. PMID- 26878079 TI - Aerobic oxidative cyclization of benzamides via meta-selective C-H tert alkylation: rapid entry to 7-alkylated isoquinolinediones. AB - A novel copper-catalyzed aerobic oxidative cyclization of benzamides via meta selective C-H tert-alkylation using AIBN and analogues as radical precursors was described. This strategy provides an elusive and rapid means to 7-tert-alkylated isoquinolinediones, as well as the construction of tertiary alkyl-aryl C(sp(3)) C(sp(2)) bonds with positional selectivity. PMID- 26878080 TI - Relationship between Glycation and Polyphenol Content and the Bioactivity of Selected Commercial Soy Milks. AB - Soy milk is a health-promoting beverage of which consumption is steadily expanding. Different bioactivities have been associated with soy products such as antioxidant capacity, anti-inflammatory properties, or decrease of cancer development risk. These activities have been related to the presence of several compounds, including polyphenols and serine protease inhibitors, although factors influencing such activities have been scarcely studied. In this study, we have determined the antioxidant capacity (ABTS and FRAP methods measured with the global antioxidant response, GAR protocol), total phenolic content, serine protease inhibitory activity, and presence of heat damage indicators in commercial soy milks. Polyphenols were primarily responsible for the antioxidant capacity of soy milks, increasing their concentration after digestion. Glycation under heat treatment might be responsible for decreasing protease inhibitory activities in soy milks. The results obtained support a role for furosine, a known marker of Maillard reaction and glycation, as a potential indicator to monitor both thermal treatment and effects on protease inhibitory activities in soy milk. The contribution of soy milk consumption to the daily intake of antioxidants and serine protease inhibitory activities is discussed. PMID- 26878078 TI - Self-assembling peptides for stem cell and tissue engineering. AB - Regenerative medicine holds great potential to address many shortcomings in current medical therapies. An emerging avenue of regenerative medicine is the use of self-assembling peptides (SAP) in conjunction with stem cells to improve the repair of damaged tissues. The specific peptide sequence, mechanical properties, and nanotopographical cues vary widely between different SAPs, many of which have been used for the regeneration of similar tissues. To evaluate the potential of SAPs to guide stem cell fate, we extensively reviewed the literature for reports of SAPs and stem cell differentiation. To portray the most accurate summary of these studies, we deliberately discuss both the successes and pitfalls, allowing us to make conclusions that span the breadth of this exciting field. We also expand on these conclusions by relating these findings to the fields of nanotopography, mechanotransduction, and the native composition of the extracellular matrix in specific tissues to identify potential directions for future research. PMID- 26878077 TI - Biomaterials-based strategies for salivary gland tissue regeneration. AB - The salivary gland is a complex, secretory tissue that produces saliva and maintains oral homeostasis. Radiation induced salivary gland atrophy, manifested as "dry mouth" or xerostomia, poses a significant clinical challenge. Tissue engineering recently has emerged as an alternative, long-term treatment strategy for xerostomia. In this review, we summarize recent efforts towards the development of functional and implantable salivary glands utilizing designed polymeric substrates or synthetic matrices/scaffolds. Although the in vitro engineering of a complex implantable salivary gland is technically challenging, opportunities exist for multidisciplinary teams to assemble implantable and secretory tissue modules by combining stem/progenitor cells found in the adult glands with biomimetic and cell-instructive materials. PMID- 26878081 TI - Consequences of Decontamination Procedures in Forensic Hair Analysis Using Metal Assisted Secondary Ion Mass Spectrometry Analysis. AB - Today, hair testing is considered to be the standard method for the detection of chronic drug abuse. Nevertheless, the differentiation between systemic exposure and external contamination remains a major challenge in the forensic interpretation of hair analysis. Nowadays, it is still impossible to directly show the difference between external contamination and use-related incorporation. Although the effects of washing procedures on the distribution of (incorporated) drugs in hair remain unknown, these decontamination procedures prior to hair analysis are considered to be indispensable in order to exclude external contamination. However, insights into the effect of decontamination protocols on levels and distribution of drugs incorporated in hair are essential to draw the correct forensic conclusions from hair analysis; we studied the consequences of these procedures on the spatial distribution of cocaine in hair using imaging mass spectrometry. Additionally, using metal-assisted secondary ion mass spectrometry, we are the first to directly show the difference between cocaine contaminated and user hair without any prior washing procedure. PMID- 26878082 TI - An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. AB - Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 (10-15%) fatalities in 2003. The causative agent of SARS has been identified as a novel human coronavirus (SARS-CoV), and its viral protease, SARS-CoV 3CL(pro), has been shown to be essential for replication and has hence been recognized as a potent drug target for SARS infection. Currently, there is no effective treatment for this epidemic despite the intensive research that has been undertaken since 2003 (over 3500 publications). This perspective focuses on the status of various efficacious anti-SARS-CoV 3CL(pro) chemotherapies discovered during the last 12 years (2003-2015) from all sources, including laboratory synthetic methods, natural products, and virtual screening. We describe here mainly peptidomimetic and small molecule inhibitors of SARS-CoV 3CL(pro). Attempts have been made to provide a complete description of the structural features and binding modes of these inhibitors under many conditions. PMID- 26878083 TI - Determinants of physician antibiotic prescribing behavior: a 3 year cohort study in Portugal. AB - Objectives Antibiotic misprescription is a major driver of resistance, which is a worldwide public health problem. Therefore, our aim is to assess the influence of the determinants of physician prescribing on the quality of antibiotic use. Methods A 3 year cohort study including all primary-care physicians working in Portugal's Central Regional Health Administration (n = 1094) was conducted. We assessed the determinants of prescribing using a pre-validated, personally addressed, reply-paid, self-administered questionnaire (sent four times to non responders, between September 2011 and February 2012) designed to collect information on physicians' attitudes to and knowledge of antibiotic prescribing as well as their socio-demographic and professional data. To evaluate antibiotic prescribing, we've calculated ESAC 12 quality indicators per physician per year, allowing us to stratify them as good or poor prescribers according to their performance on those indicators. Associations between determinants and outcomes were fitted with generalized linear mixed models. Results The overall response rate was 46.1%. Emergency activity (OR [95% CI] = 0.29 [0.16-0.54]; p < 0.05) and workload (number of patients seen per day: OR [95% CI] = 0.97 [0.94-1.00]; p < 0.05; number of patients seen per week in emergencies: OR [95% CI] = 0.98 [0.97 0.99]; p < 0.05) were both related to poor quality of antibiotic prescribing. Statistically significant odds ratios were also obtained for ignorance (IqOR [95% CI] = 2.14 [1.31-3.52]), complacency (1/IqOR [95% CI] = 1.19 [1.01-1.41]) and responsibility of others (1/IqOR [95% CI] = 1.78 [1.10-3.06]). Conclusions The above results serve to emphasize workload, working at emergency departments and physicians' attitudes identified as critical factors affecting antibiotic prescribing. This provides new insights for clinicians, researchers and policy makers when it comes to developing and improving the clinical and economic outcomes of antibiotic use. Key limitations of the study included the difficulty of results extrapolation and the limitations of the stratification method based on the antibiotic prescribing quality indicators. PMID- 26878084 TI - Glucosamine-anchored doxorubicin-loaded targeted nano-niosomes: pharmacokinetic, toxicity and pharmacodynamic evaluation. AB - BACKGROUND: Efficacy of anticancer drug is limited due to non-selectivity and toxicities allied with the drug; therefore the heart of the present work is to formulate drug delivery systems targeted selectively towards cancer cells with minimal toxicity to normal cells. PURPOSE: Targeted drug delivery system of doxorubicin (DOX)-loaded niosomes using synthesized N-lauryl glucosamine (NLG) as a targeting ligand. METHODS: NLG-anchored DOX niosomes were developed using ethanol injection method. RESULTS: Developed niosomes had particle size <150 nm and high entrapment efficiency ~90%. In vivo pharmacokinetics exhibited long circulating nature of targeted niosomes with improved bioavailability, which significantly reduced CL and Vd than DOX solution and non-targeted niosomes (35 fold and 2.5 fold, respectively). Tissue-distribution study and enzymatic assays revealed higher concentration of DOX solution in heart while no toxicity to major organs with developed targeted niosomes was observed. Solid skin melanoma tumor model in mice manifested the commendable targeting potential of targeted niosomes with significant reduction in tumor volume and high % survival rate without drop in body weight in comparison with DOX solution and non-targeted niosomes of DOX. CONCLUSION: The glucosamine-anchored DOX-loaded targeted niosomes showed its potential in cancer targeted drug therapy with reduced toxicity. Abbreviations ALT alanine transaminase CL clearance CPK creatinine phosphokinase DOX doxorubicin EDC.HCL ethyl carbidimide hydrochloride GLUT glucose transporter GSH glutathione S-transferase LDH lactate dehydrogenase LHRH luteinizing hormone releasing hormone MDA malonaldehyde NHS N-hydroxy succinimide NLG N-lauryl glucosamine NTAR DoxNio non-targeted doxorubicin niosomes PBS phosphate buffer saline RGD argynyl glycyl aspartic acid SGOT serum glutamate oxaloacetate transaminase SGPT serum glutamate pyruvate transaminase SOD superoxide dismutase TAR DoxNio targeted doxorubicin niosomes Vd volume of distribution. PMID- 26878085 TI - Metal-Organic Frameworks as Platforms for Functional Materials. AB - Discoveries of novel functional materials have played very important roles to the development of science and technologies and thus to benefit our daily life. Among the diverse materials, metal-organic framework (MOF) materials are rapidly emerging as a unique type of porous and organic/inorganic hybrid materials which can be simply self-assembled from their corresponding inorganic metal ions/clusters with organic linkers, and can be straightforwardly characterized by various analytical methods. In terms of porosity, they are superior to other well known porous materials such as zeolites and carbon materials; exhibiting extremely high porosity with surface area up to 7000 m(2)/g, tunable pore sizes, and metrics through the interplay of both organic and inorganic components with the pore sizes ranging from 3 to 100 A, and lowest framework density down to 0.13 g/cm(3). Such unique features have enabled metal-organic frameworks to exhibit great potentials for a broad range of applications in gas storage, gas separations, enantioselective separations, heterogeneous catalysis, chemical sensing and drug delivery. On the other hand, metal-organic frameworks can be also considered as organic/inorganic self-assembled hybrid materials, we can take advantages of the physical and chemical properties of both organic and inorganic components to develop their functional optical, photonic, and magnetic materials. Furthermore, the pores within MOFs can also be utilized to encapsulate a large number of different species of diverse functions, so a variety of functional MOF/composite materials can be readily synthesized. In this Account, we describe our recent research progress on pore and function engineering to develop functional MOF materials. We have been able to tune and optimize pore spaces, immobilize specific functional groups, and introduce chiral pore environments to target MOF materials for methane storage, light hydrocarbon separations, enantioselective recognitions, carbon dioxide capture, and separations. The intrinsic optical and photonic properties of metal ions and organic ligands, and guest molecules and/or ions can be collaboratively assembled and/or encapsulated into their frameworks, so we have realized a series of novel MOF materials as ratiometric luminescent thermometers, O2 sensors, white-light-emitting materials, nonlinear optical materials, two-photon pumped lasing materials, and two-photon responsive materials for 3D patterning and data storage. Thanks to the interplay of the dual functionalities of metal-organic frameworks (the inherent porosity, and the intrinsic physical and chemical properties of inorganic and organic building blocks and encapsulated guest species), our research efforts have led to the development of functional MOF materials beyond our initial imaginations. PMID- 26878086 TI - Cellular environment-responsive nanomaterials for use in gene and siRNA delivery: molecular design for biomembrane destabilization and intracellular collapse. AB - INTRODUCTION: The development of gene and nucleic acid-based medication is one of the ultimate strategies in the research field of personalized medicine. For the desired function of a gene or siRNA, these molecules need to be delivered to the appropriate organelle (i.e. nucleus and cytoplasm, respectively). AREAS COVERED: The topics covered herein are rational design in order to control the pharmacokinetics, intracellular trafficking and release (decondensation or decapsulation) of the intended material. Since the endosome and cytoplasm are acidic (endosome) and reducing (cytoplasm) environments, respectively, a large variety of the materials have been developed that induce destabilization of endosome via its protonation, or are spontaneously collapsed in the cytoplasm. Finally, we propose materials (SS-cleavable and pH-activated lipid-like materials: ssPalm) that mount these sensing motifs, i.e., a positive charging unit in response to the acid environment (tertiary amines) and a cleavage unit (disulfide bonding) that is responsive to an reducing environment, respectively. EXPERT OPINION: Currently, the main target of the nanocarrier-mediated siRNA delivery systems is liver. The targeting of non-hepatic tissue is the next challenge. In this case, the design of neutral particle with well-organized intracellular trafficking, as well as an identification of the promising ligand is needed. PMID- 26878087 TI - Evaluation of alpha-Globin Gene Mutations Among Different Ethnic Groups in Khuzestan Province, Southwest Iran. AB - alpha-Thalassemia (alpha-thal) is one of the most common inherited hemoglobin (Hb) disorders in the world. In addition to large deletions, over 50 different alpha-thal point mutations were detected around the world, thus, patients showed different phenotypes with regard to genotype. This study evaluated the genetic frequency of alpha-thal in Khuzestan Province, Southwest Iran, to help implement premarital and prenatal screening programs. The study was conducted on couples proposing to get married and parents who were referred to the genetic center of Shafa Hospital, Ahvaz, Iran, for prenatal diagnosis (PND) in 2012. Genomic DNA was purified by the salting-out method and tested using multiplex gap-polymerase chain reaction (gap-PCR), amplification refractory mutation system-PCR (ARMS PCR), reverse hybridization test strips and DNA sequencing. Overall, 11 mutations were found on the alpha-globin genes. Based on gene frequency, the most common mutant allele was -alpha(3.7) (rightward) (71.3%) followed by the two gene deletion - -(MED) (9.7%). Other common mutations were alpha(codon 19)alpha (GCG>GC-, alpha2) (8.4%), the polyadenylation (polyA1) site alpha(polyA1)alpha (AATAAA>AATAAG) (2.8%), and alpha(-5 nt)alpha (-TGAGG) (2.0%). In addition, an extremely rare mutation at alpha(codon 21)alpha [Hb Fontainebleau, HBA2: c.64G > C (or HBA1)] was also found. The results of this study are critical for correct diagnosis of alpha-thal carriers, premarriage counseling and PND. This study suggests that the distribution of mutations on the alpha-globin genes differs among the ethnic groups in Khuzestan Province as well as in other provinces. PMID- 26878089 TI - Synthesis of a Model Tetracyclic Core Structure of Calyciphylline B-Type Alkaloids. AB - Herein, we report the enantioselective synthesis of a functionalized aza octahydropentalene and its elaboration to a model tetracyclic core structure of calyciphylline B-type alkaloids. PMID- 26878088 TI - Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. AB - INTRODUCTION: Carbonic anhydrase inhibitors (CAIs) of the sulfonamide and sulfamate type are clinically used drugs as diuretics, antiglaucoma, antiepileptic, antiobesity and anti-high altitude disease agents. Anticancer agents based on CAIs are also in clinical development for the management of hypoxic, metastatic tumors. Acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide are mainly used as antiglaucoma drugs, sulthiame, topiramate and zonisamide as antiepileptic/antiobesity agents, celecoxib and polmacoxib are dual carbonic anhydrase/cycloxygenase inhibitors. Girentuximab, a monoclonal antibody and SLC-0111, a sulfonamide inhibitor, are in clinical trials as anticancer agents. AREAS COVERED: The drug interactions with many classes of pharmacological agents are reviewed. Some of these drugs, such as acetazolamide, topiramate and celecoxib show a large number of interactions with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, antiepileptics, immunosupressants, anticholinesterase drugs, beta-blockers, anesthetics, oral contraceptives, anticancer agents, antifungals, anti-mycobacterials, lithium, metformin and clopidogrel. EXPERT OPINION: The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high. There are also synergistic effects between CAIs and some NSAIDs, anticancer agents and benzodiazepines for the management of cystoid macular edema, some tumor types and neuropathic pain, respectively. PMID- 26878090 TI - Eliminating dual-task costs by minimizing crosstalk between tasks: The role of modality and feature pairings. AB - We tested the independent influences of two content-based factors on dual-task costs, and on the parallel processing ability: The pairing of S-R modalities and the pairing of relevant features between stimuli and responses of two tasks. The two pairing factors were realized across four dual-task groups. Within each group the two tasks comprised two different stimulus modalities (visual and auditory), two different relevant stimulus features (spatial and verbal) and two response modalities (manual and vocal). Pairings of S-R modalities (standard: visual manual and auditory-vocal, non-standard: visual-vocal and auditory-manual) and feature pairings (standard: spatial-manual and verbal-vocal, non-standard: spatial-vocal and verbal-manual) varied across groups. All participants practiced their respective dual-task combination in a paradigm with simultaneous stimulus onset before being transferred to a psychological refractory period paradigm varying stimulus-onset asynchrony. A comparison at the end of practice revealed similar dual-task costs and similar pairing effects in both paradigms. Dual-task costs depended on modality and feature pairings. Groups training with non standard feature pairings (i.e., verbal stimulus features mapped to spatially separated response keys, or spatial stimulus features mapped to verbal responses) and non-standard modality pairings (i.e., auditory stimulus mapped to manual response, or visual stimulus mapped to vocal responses) had higher dual-task costs than respective standard pairings. In contrast, irrespective of modality pairing dual-task costs virtually disappeared with standard feature pairings after practice in both paradigms. The results can be explained by crosstalk between feature-binding processes for the two tasks. Crosstalk was present for non-standard but absent for standard feature pairings. Therefore, standard feature pairings enabled parallel processing at the end of practice. PMID- 26878091 TI - Longitudinal biobanks-based study on the joint effects of infections, nutrition and hormones on risk of prostate cancer. AB - Background To evaluate the individual and combined effects of enterolactone, vitamin D, free testosterone, Chlamydia trachomatis and HPV-18 on the risk of prostate cancer in a large population-based biochemical material that combined three Nordic serum sample banks. Material and methods A joint cohort of 209 000 healthy men was followed using cancer registry linkages. From this cohort altogether 699 incident cases of prostate cancer were identified. Four controls were selected by incidence density sampling and matching for country, age and date of the blood sampling. Complete data for all investigated exposures was available for 483 eligible cases and 1055 eligible controls. Multivariate regression analyses were performed to investigate the solitary and combined effects. Results The solitary effects were small. Significantly increased risk [rate ratio 1.6 (95% CI 1.0-2.5)] was found in those seronegative for C. trachomatis infection. The joint effect in risk levels of enterolactone and vitamin D was antagonistic [observed rate ratio (RR) 1.4 (1.0-2.1), expected RR 2.0 (1.0-4.1)] as well as that of HPV-18 and C. trachomatis [observed RR 1.9 (0.8 4.5), expected RR 9.9 (1.1-87.0)]. Conclusion A large follow-up study combining data from several previously investigated exposures to investigate joint effects found no evidence that exposure to two risk factors would increase the risk of prostate cancer from that expected on basis of exposure to one risk factor. If anything, the results were consistent with antagonistic interactions. PMID- 26878092 TI - Does polycystic ovary syndrome affect cognition? A functional magnetic resonance imaging study exploring working memory. AB - OBJECTIVE: To study effects of overexposure to androgens and subsequent antiandrogenic treatment on brain activity during working memory processes in women with polycystic ovary syndrome (PCOS). DESIGN: In this longitudinal study, working memory function was evaluated with the use of functional magnetic resonance imaging (MRI) in women with PCOS before and after antiandrogenic treatment. SETTING: Department of reproductive medicine, university medical center. PATIENT(S): Fourteen women with PCOS and with hyperandrogenism and 20 healthy control women without any features of PCOS or other hormonal disorders. INTERVENTION(S): Antiandrogenic hormone treatment. MAIN OUTCOME MEASURE(S): Functional MRI response during a working memory task. RESULT(S): At baseline women with PCOS showed more activation than the control group within the right superior parietal lobe and the inferior parietal lobe during task (all memory conditions). Task performance (speed and accuracy) did not differ between the groups. After antiandrogenic treatment the difference in overall brain activity between the groups disappeared and accuracy in the high memory load condition of the working memory task increased in women with PCOS. CONCLUSION(S): Women with PCOS may need additional neural resources during a working memory task compared with women without PCOS, suggesting less efficient executive functioning. This inefficiency may have effects on daily life functioning of women with PCOS. Antiandrogenic treatment appears to have a beneficial effect on this area of cognitive functioning. CLINICAL TRIAL REGISTRATION NUMBER: NTR2493. PMID- 26878093 TI - Proposal for a national registry to monitor women with Turner syndrome seeking assisted reproductive technology. PMID- 26878094 TI - An Esterase from Anaerobic Clostridium hathewayi Can Hydrolyze Aliphatic-Aromatic Polyesters. AB - Recently, a variety of biodegradable polymers have been developed as alternatives to recalcitrant materials. Although many studies on polyester biodegradability have focused on aerobic environments, there is much less known on biodegradation of polyesters in natural and artificial anaerobic habitats. Consequently, the potential of anaerobic biogas sludge to hydrolyze the synthetic compostable polyester PBAT (poly(butylene adipate-co-butylene terephthalate) was evaluated in this study. On the basis of reverse-phase high-performance liquid chromatography (RP-HPLC) analysis, accumulation of terephthalic acid (Ta) was observed in all anaerobic batches within the first 14 days. Thereafter, a decline of Ta was observed, which occurred presumably due to consumption by the microbial population. The esterase Chath_Est1 from the anaerobic risk 1 strain Clostridium hathewayi DSM-13479 was found to hydrolyze PBAT. Detailed characterization of this esterase including elucidation of the crystal structure was performed. The crystal structure indicates that Chath_Est1 belongs to the alpha/beta-hydrolases family. This study gives a clear hint that also micro-organisms in anaerobic habitats can degrade manmade PBAT. PMID- 26878096 TI - Comment on Castillo et al. (2015). PMID- 26878095 TI - Cross-cultural differences and similarities underlying other-race effects for facial identity and expression. AB - Perceptual advantages for own-race compared to other-race faces have been demonstrated for the recognition of facial identity and expression. However, these effects have not been investigated in the same study with measures that can determine the extent of cross-cultural agreement as well as differences. To address this issue, we used a photo sorting task in which Chinese and Caucasian participants were asked to sort photographs of Chinese or Caucasian faces by identity or by expression. This paradigm matched the task demands of identity and expression recognition and avoided constrained forced-choice or verbal labelling requirements. Other-race effects of comparable magnitude were found across the identity and expression tasks. Caucasian participants made more confusion errors for the identities and expressions of Chinese than Caucasian faces, while Chinese participants made more confusion errors for the identities and expressions of Caucasian than Chinese faces. However, analyses of the patterns of responses across groups of participants revealed a considerable amount of underlying cross cultural agreement. These findings suggest that widely repeated claims that members of other cultures "all look the same" overstate the cultural differences. PMID- 26878097 TI - Muscle coordination during breaststroke swimming: Comparison between elite swimmers and beginners. AB - The present study aimed to compare muscle coordination strategies of the upper and lower limb muscles between beginners and elite breaststroke swimmers. Surface electromyography (EMG) of eight muscles was recorded in 16 swimmers (8 elite, 8 beginners) during a 25 m swimming breaststroke at 100% of maximal effort. A decomposition algorithm was used to identify the muscle synergies that represent the temporal and spatial organisation of muscle coordination. Between-groups indices of similarity and lag times were calculated. Individual muscle patterns were moderately to highly similar between groups (between-group indices range: 0.61 to 0.84). Significant differences were found in terms of lag time for pectoralis major (P < 0.05), biceps brachii, rectus femoris and tibialis anterior (P < 0.01), indicating an earlier activation for these muscles in beginners compared to elites (range: -13.2 to -3.8% of the swimming cycle). Three muscle synergies were identified for both beginners and elites. Although their composition was similar between populations, the third synergy exhibited a high within-group variability. Moderate to high indices of similarity were found for the shape of synergy activation coefficients (range: 0.63 to 0.88) but there was a significant backward shift (-8.4% of the swimming cycle) in synergy #2 for beginners compared to elites. This time shift suggested differences in the global arm-to-leg coordination. These results indicate that the synergistic organisation of muscle coordination during breaststroke swimming is not profoundly affected by expertise. However, specific timing adjustments were observed between lower and upper limbs. PMID- 26878098 TI - Flicking technique for microencapsulation of cells in calcium alginate leading to the microtissue formation. AB - Microbeads have wide applications in biomedical engineering field that include drug delivery, encapsulation of biomolecules, tissue padding and tissue regeneration. In this paper, we report a simple, yet efficient, flicking technique to produce microcapsules of calcium alginate at a narrow distribution of size. The system consists of an infusion pump and a customised flicker that taps the syringe needle for dispersing microcapsules of sodium alginate that polymerised in the calcium chloride solution. The flow rate of the syringe pump and the velocity of the flicker were studied to achieve a well controlled and tunable size distribution of microbeads ranging from 200 to 400 MUm. At a flow rate of 4 MUl/min and flicking rate of 80 rpm, a narrow size distribution of microbeads were produced. Via this technique, HaCaT cells were encapsulated in calcium alginate microbeads that grown into microtissues with a size ranging from 100 to 300 MUm after two weeks of culture. These microtissues could be potentially useful for pharmacological application. PMID- 26878100 TI - A critical evaluation of second-generation AF ablation technologies: cryoballoons and contact forces. PMID- 26878099 TI - Is there a place for cardiovascular magnetic resonance conditional devices in systemic inflammatory diseases? AB - Rhythm disturbances and sudden cardiac death (SCD) are important manifestations of cardiac involvement in systemic inflammatory diseases (SID). The commonest events demanding the implantation of a device include ventricular tachycardia and atrioventricular block, mainly diagnosed in sarcoidosis, systemic lupus erythematosus and scleroderma. In SCD, cardiac magnetic resonance (CMR) identified areas of late gadolinium enhancement (LGE) in 71% and provided an arrhythmic substrate in 76%, while during the follow-up, the extent of LGE identified a subgroup at increased risk for future adverse events. CMR has been successfully used for detection of cardiac disease in SID, including myocarditis, coronary, microvascular and valvular disease. Additionally, SIDs have a higher probability to need MRI scanning of other organs, due to their systemic disease. These reasons support the necessity of an MRI conditional device in SIDs. A broad selection of devices, approved for the MRI environment under defined conditions allows the safe and accurate scanning of SID patients. PMID- 26878101 TI - Comparison of the effects of voluntary termination of pregnancy and uterine evacuation for medical reasons on female sexual function. AB - OBJECTIVE: A wide spectrum of emotions are experienced during abortion, including anxiety, sadness and grief, guilt, pessimism about future pregnancies, disturbed self-perception and loss of confidence in intimate relationships. This study aimed to compare the short-term effects of legal voluntary termination of pregnancy with uterine evacuation for medical reasons on female sexual function. STUDY DESIGN: The study group was comprised of 50 patients admitted to the Family Planning Clinic for legal voluntary termination of pregnancy <10 weeks of gestation, and the control group was comprised of 50 patients who underwent manual vacuum aspiration of the products of conception for medical reasons (e.g. inevitable abortion, incomplete abortion, fetal abnormality and teratogenic drug use). Female sexual function in the two groups was evaluated using the Golombok Rust Inventory of Sexual Satisfaction (GRISS). GRISS scores immediately before and 3 months after termination of pregnancy were compared within each group and between the two groups. RESULTS: Mean total GRISS scores before and after termination of pregnancy were 5.33 and 8.12 in the study group, and 6.02 and 6.4 in the control group, respectively (p<0.05). The increase in GRISS scores for both groups indicated deterioration in sexual function (p=0.000 and p=0.016, respectively). Three months after termination of pregnancy, the total GRISS score was significantly higher in the study group compared with the control group (8.12 vs 6.4, p<0.05). CONCLUSION: Female sexual dysfunction is a complicated concept that is affected by multiple factors over a woman's lifetime. It is important to consider female sexual function as a part of reproductive health, with a close relationship with contraception. As such, patients should receive counselling about sexual function and contraception as part of comprehensive abortion care. PMID- 26878102 TI - Translation, cross-cultural adaptation and validity of the Brazilian version of the Foot and Ankle Ability Measure questionnaire. AB - PURPOSE: To translate and cross-culturally adapt the Foot and Ankle Ability Measure (FAAM) questionnaire and verify the psychometric properties of the Brazilian-Portuguese version of this instrument. METHODS: Analysis of validity was carried out by applying the Rasch model and evaluating correlations with the Short Form-36 (SF-36) Physical Function (PF) subscale. Test-retest reliability and internal consistency were analyzed with the intraclass correlation coefficient (ICC2,1) and Cronbach's alpha tests, respectively. RESULTS: Ninety subjects with various foot and ankle musculoskeletal disorders (age 37.05 SD 10.49 years) were included. The ICC2,1 was 0.88 and 0.82 with Cronbach's alphas of 0.93 and 0.90 for the "Activities of Daily Living" (ADL) and "Sports" subscales, respectively. Correlations with the SF-36 PF were 0.78 (p < 0.01, CI95: 0.62-0.87) and 0.65 (p < 0.01, CI95: 0.45-0.79) for the ADL and Sports subscales, respectively. Item reliability indices in Rasch analysis were 0.91 (ADL) and 0.84 (Sports). Three items from the ADL subscale (14.2%) did not match the expectations of the model. All items from the Sports subscale fit the model. CONCLUSIONS: There is evidence of validity and reliability of the FAAM-Brazil. Rasch analysis indicated that three items of the ADL subscale did not fit the model in the sample studied. Implications for Rehabilitation Self-report questionnaires are commonly used in both clinical practice and research because of their ability to efficiently collect information. If the instrument is created properly, the information collected can be used to interpret the effect of clinical conditions on physical function. The Foot and Ankle Ability Measure (FAAM) is an evaluative instrument that assesses functional limitations for those with foot- and ankle-related disorders. It was translated into four languages and has evidence of validity, reliability, and responsiveness. Evidence of validity and reliability is provided for the FAAM-Brazil when applied to subjects with a wide range of foot and ankle musculoskeletal disorders. PMID- 26878103 TI - Multiple giant coronary artery aneurysms: a case report. AB - BACKGROUND: Coronary artery aneurysm is defined as a localized area of dilatation exceeding the diameter of the adjacent normal arterial segment by 50%. Giant aneurysms are those aneurysms that measure greater than 2cm in diameter. There have been many pathologic diseases, including atherosclerosis, that have been implicated in the development of coronary artery aneurysms. MATERIALS AND METHODS: We report a case of a 61-year-old African American male with multiple comorbidities including hypertension, congestive heart failure, abdominal aortic aneurysm, and bilateral iliac aneurysms, who was admitted to our hospital with exacerbation of congestive heart failure. Less than 2weeks after admission, the patient suffered cardiac arrest while receiving dialysis and was unresponsive to resuscitative measures. FINDINGS: Autopsy was performed and revealed significant cardiomyopathy and giant coronary artery aneurysms involving the left anterior descending, left circumflex, and right coronary arteries. Both ventricles showed hypertrophy and dilation with multifocal areas of chronic myocardial scarring. CONCLUSIONS: Coronary artery aneurysms and giant coronary artery aneurysms are an uncommon. As there are few reported cases in the literature, the cause, detection, and treatment of this disease are still largely unknown. PMID- 26878104 TI - Multiscale modeling of virus replication and spread. AB - Replication and spread of human viruses is based on the simultaneous exploitation of many different host functions, bridging multiple scales in space and time. Mathematical modeling is essential to obtain a systems-level understanding of how human viruses manage to proceed through their life cycles. Here, we review corresponding advances for viral systems of large medical relevance, such as human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV). We will outline how the combination of mathematical models and experimental data has advanced our quantitative knowledge about various processes of these pathogens, and how novel quantitative approaches promise to fill remaining gaps. PMID- 26878106 TI - Asymmetric sequential Au(i)/chiral tertiary amine catalysis: an enone formation/cyanosilylation sequence to synthesize optically active 3 alkenyloxindoles from diazooxindoles. AB - An unprecedented sequential gold-catalyzed enone-formation and bifunctional tertiary amine mediated asymmetric cyanosilylation reaction is developed, allowing the highly enantioselective synthesis of 3-alkenyloxindoles from diazooxindoles, furans and trimethylsilyl cyanide (TMSCN). PMID- 26878105 TI - Higher PUFA and n-3 PUFA, conjugated linoleic acid, alpha-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses. AB - Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI -1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of alpha-linolenic acid (ALA), very long chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI -122, 20) % and 93 (95 % CI -116, -70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher alpha-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences. PMID- 26878108 TI - Tuning the hydrogen evolution activity of MS2 (M = Mo or Nb) monolayers by strain engineering. AB - Strain engineering is an effective strategy to tune the electronic, magnetic and optical properties of atomically thin materials like graphene and monolayer transition-metal dichalcogenides (m-TMDs). Using first-principles calculations, we show that strain is also effective for tuning the catalytic activity of m-MS2 (M = Mo or Nb) towards the hydrogen evolution reaction (HER), which is essential for electrochemical hydrogen generation from water splitting. A wide strain range covering both compressive (0-6%) and tensile (0-10%) regions is considered. It is found that biaxial tensile strain can enhance the HER activity more effectively than uniaxial tensile strain, while compressive strain deteriorates the HER activity. Compared with monolayer 1T-NbS2, monolayers 1T-MoS2 and 1H-NbS2 exhibit better strain tunability towards their HER activities since more active sites can be induced with increasing strain. In contrast, monolayer 1H-MoS2 is catalytically inert in the considered strain range because H adsorption is too weak. We demonstrate that tensile strain can lead to decrease of the adiabatic proton affinity but simultaneously a larger magnitude of increase of the adiabatic electron affinity, thus enhancing the catalytic activity. Electronic structure calculations show that tensile strain can activate the relatively inert inner valence electrons and enlarge the d-band exchange splitting, both of which induce destabilization of the system and enhancement of catalytic activity. PMID- 26878107 TI - Performance of in-pixel circuits for photon counting arrays (PCAs) based on polycrystalline silicon TFTs. AB - Photon counting arrays (PCAs), defined as pixelated imagers which measure the absorbed energy of x-ray photons individually and record this information digitally, are of increasing clinical interest. A number of PCA prototypes with a 1 mm pixel-to-pixel pitch have recently been fabricated with polycrystalline silicon (poly-Si)-a thin-film technology capable of creating monolithic imagers of a size commensurate with human anatomy. In this study, analog and digital simulation frameworks were developed to provide insight into the influence of individual poly-Si transistors on pixel circuit performance-information that is not readily available through empirical means. The simulation frameworks were used to characterize the circuit designs employed in the prototypes. The analog framework, which determines the noise produced by individual transistors, was used to estimate energy resolution, as well as to identify which transistors contribute the most noise. The digital framework, which analyzes how well circuits function in the presence of significant variations in transistor properties, was used to estimate how fast a circuit can produce an output (referred to as output count rate). In addition, an algorithm was developed and used to estimate the minimum pixel pitch that could be achieved for the pixel circuits of the current prototypes. The simulation frameworks predict that the analog component of the PCA prototypes could have energy resolution as low as 8.9% full width at half maximum (FWHM) at 70 keV; and the digital components should work well even in the presence of significant thin-film transistor (TFT) variations, with the fastest component having output count rates as high as 3 MHz. Finally, based on conceivable improvements in the underlying fabrication process, the algorithm predicts that the 1 mm pitch of the current PCA prototypes could be reduced significantly, potentially to between ~240 and 290 MUm. PMID- 26878109 TI - A facile chemical-mechanical polishing lift-off transfer process toward large scale Cu(In,Ga)Se2 thin-film solar cells on arbitrary substrates. AB - The fabrication of Cu(In,Ga)Se2 (CIGS) solar cells on flexible substrates is a non-trivial task due to thermal and ion diffusion related issues. In order to circumvent these issues, we have developed a chemical-mechanical polishing lift off (CMPL) transfer process, enabling the direct transfer of CIGS solar cells from conventional soda-lime glass (SLG) onto arbitrary flexible substrates up to 4 cm(2) in size. The structural and compositional nature of the pre- and post transferred films is examined using electron microscopy, X-ray diffraction analysis, Raman and photoluminescence spectroscopy. We demonstrate the fabrication of solar cells on a range of flexible substrates while being able to maintain 75% cell efficiency (eta) when compared to pre-transferred solar cells. The results obtained in this work suggest that our transfer process offers a highly promising approach toward large scale fabrication of CIGS-based solar cells on a wide variety of flexible substrates, suitable for use in the large scale CIGS photovoltaic industry. PMID- 26878110 TI - The effect of chlorpyrifos on thermogenic capacity of bank voles selected for increased aerobic exercise metabolism. AB - Agro-chemicals potentially cause adverse effects in non-target organisms. The rate of animal energy metabolism can influence their susceptibility to pesticides by influencing food consumption, biotransformation and elimination rates of toxicants. We used experimental evolution to study the effects of inherent differences in energy metabolism rate and exposure to the organophosphate insecticide, chlorpyrifos (CPF) on thermogenic capacity in a wild rodent, the bank vole (Myodes = Clethrionomys glareolus). The voles were sampled from four replicate lines selected for high swim-induced aerobic metabolism (A) and four unselected control (C) lines. Thermogenic capacity, measured as the maximum cold induced rate of oxygen consumption (VO2cold), was higher in the A - than C lines, and it decreased after continuous exposure to CPF via food or after a single dose administered via oral gavage, but only when measured shortly after exposure. VO2cold measured 24 h after repeated exposure was not affected. In addition, gavage with a single dose led to decreased food consumption and loss in body mass. Importantly, the adverse effects of CPF did not differ between the selected and control lines. Therefore, exposure to CPF has adverse effects on thermoregulatory performance and energy balance in this species. The effects are short-lived and their magnitude is not associated with the inherent level of energy metabolism. Even without severe symptoms of poisoning, fitness can be compromised under harsh environmental conditions, such as cold and wet weather. PMID- 26878111 TI - A Trichoderma atroviride stress-activated MAPK pathway integrates stress and light signals. AB - Cells possess stress-activated protein kinase (SAPK) signalling pathways, which are activated practically in response to any cellular insult, regulating responses for survival and adaptation to harmful environmental changes. To understand the function of SAPK pathways in T. atroviride, mutants lacking the MAPKK Pbs2 and the MAPK Tmk3 were analysed under several cellular stresses, and in their response to light. All mutants were highly sensitive to cellular insults such as osmotic and oxidative stress, cell wall damage, high temperature, cadmium, and UV irradiation. Under oxidative stress, the Tmk3 pathway showed specific roles during development, which in conidia are essential for tolerance to oxidant agents and appear to play a minor role in mycelia. The function of this pathway was more evident in Deltapbs2 and Deltatmk3 mutant strains when combining oxidative stress or cell wall damage with light. Light stimulates tolerance to osmotic stress through Tmk3 independently of the photoreceptor Blr1. Strikingly, photoconidiation and expression of blue light regulated genes was severally affected in Deltatmk3 and Deltapbs2 strains, indicating that this pathway regulates light responses. Furthermore, Tmk3 was rapidly phosphorylated upon light exposure. Thus, our data indicate that Tmk3 signalling cooperates with the Blr photoreceptor complex in the activation of gene expression. PMID- 26878112 TI - A hematopoietic cell-driven mechanism involving SLAMF6 receptor, SAP adaptors and SHP-1 phosphatase regulates NK cell education. AB - Activation of natural killer (NK) cells by hematopoietic target cells is controlled by the SLAM family of receptors and by the associated SAP family of adaptors. Here we found that SLAM receptors also enhanced NK cell activation by nonhematopoietic target cells, which lack ligands for SLAM receptors. This function was mediated by SLAMF6, a homotypic SLAM receptor found on NK cells and other hematopoietic cells, and was regulated by SAP adaptors, which uncoupled SLAM receptors from phosphatase SHP-1 and diminished the effect of SLAMF6 on NK cell responsiveness toward nonhematopoietic cells. Thus, in addition to their role in NK cell activation by hematopoietic cells, the SLAM-SAP pathways influence responsiveness toward nonhematopoietic targets by a process akin to NK cell 'education'. PMID- 26878113 TI - The heterogeneity of human CD127(+) innate lymphoid cells revealed by single-cell RNA sequencing. AB - Innate lymphoid cells (ILCs) are increasingly appreciated as important participants in homeostasis and inflammation. Substantial plasticity and heterogeneity among ILC populations have been reported. Here we have delineated the heterogeneity of human ILCs through single-cell RNA sequencing of several hundreds of individual tonsil CD127(+) ILCs and natural killer (NK) cells. Unbiased transcriptional clustering revealed four distinct populations, corresponding to ILC1 cells, ILC2 cells, ILC3 cells and NK cells, with their respective transcriptomes recapitulating known as well as unknown transcriptional profiles. The single-cell resolution additionally divulged three transcriptionally and functionally diverse subpopulations of ILC3 cells. Our systematic comparison of single-cell transcriptional variation within and between ILC populations provides new insight into ILC biology during homeostasis, with additional implications for dysregulation of the immune system. PMID- 26878115 TI - Photophysical properties of octupolar triazatruxene-based chromophores. AB - The photophysical properties of three octupolar chromophores containing planar triazatruxene (TAT) as the central electron donor with different electron withdrawing groups in the tribranched arrangement have been systematically investigated by means of steady state and transient spectroscopy. The multidimensional intramolecular charge transfer (ICT) properties of these tribranched chromophores related to the observed two-photon absorption (TPA) properties are explored by estimating the TPA essential factors (Mge and DeltaMUge). Besides the large Stokes shift between steady state absorption and fluorescence spectra in different polar solvents, photoinduced ICT was further demonstrated by quantum-chemical calculations and transient absorption measurements. Both quantum calculations and spectral experiments show that a multidimensional ICT occurs from the electron-rich core to the electron-deficient periphery of these TAT derivatives. The results of solvation effects and the dynamics of the excited states show that the excited states of these three chromophores tend to exhibit an excitation localization on one of the dipolar branches, which is beneficial to achieve large Mge and DeltaMUge, thus leading to enhanced TPA properties. PMID- 26878114 TI - The cellular composition of the human immune system is shaped by age and cohabitation. AB - Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system. PMID- 26878117 TI - [Ocular Herpesviridae Infections - Laboratory Diagnostics and Therapeutics]. PMID- 26878118 TI - [Non-Infectious Conjunctiva Diseases]. PMID- 26878116 TI - Heterogeneity of Matrin 3 in the developing and aging murine central nervous system. AB - Mutations in the MATR3 gene encoding the nucleotide binding protein Matrin 3 have recently been identified as causing a subset of familial amyotrophic lateral sclerosis (fALS) and more rarely causing distal myopathy. Translating the identification of MATR3 mutations into an understanding of disease pathogenesis and the creation of mouse models requires a complete understanding of normal Matrin 3 levels and distribution in vivo. Consequently, we examined the levels of murine Matrin 3 in body tissues and regions of the central nervous system (CNS). We observed a significant degree of variability in Matrin 3 protein levels among different tissues of adult animals, with the highest levels found in reproductive organs and the lowest in muscle. Within the adult CNS, Matrin 3 levels were lowest in spinal cord. Further, we found that Matrin 3 declines significantly in CNS through early development and young adulthood before stabilizing. As previously reported, antibodies to Matrin 3 primarily stain nuclei, but the intensity of staining was not uniform in all nuclei. The low levels of Matrin 3 in spinal cord and muscle could mean that that these tissues are particularly vulnerable to alterations in Matrin 3 function. Our study is the first to characterize endogenous Matrin 3 in rodents across the lifespan, providing the groundwork for deciphering disease mechanisms and developing mouse models of MATR3-linked ALS. J. Comp. Neurol. 524:2740-2752, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26878119 TI - [Topical Anti-Inflammatory Therapy Options]. PMID- 26878120 TI - Refractory status epilepticus and glutamic acid decarboxylase antibodies in adults: presentation, treatment and outcomes. AB - Glutamic acid decarboxylase antibodies (GAD-Abs) have been implicated in refractory epilepsy. The association with refractory status epilepticus in adults has been rarely described. We discuss our experience in managing three adult patients who presented with refractory status epilepticus associated with GAD Abs. Case series with retrospective chart and literature review. Three patients without pre-existing epilepsy who presented to our institution with generalized seizures between 2013 and 2014 were identified. Seizures proved refractory to first and second-line therapies and persisted beyond 24 hours. Patient 1 was a 22 year-old female who had elevated serum GAD-Ab titres at 0.49 mmol/l (normal: <0.02) and was treated with multiple immuno- and chemotherapies, with eventual partial seizure control. Patient 2 was a 61-year-old black female whose serum GAD Ab titre was 0.08 mmol/l. EEG showed persistent generalized periodic discharges despite maximized therapy with anticonvulsants but no immunotherapy, resulting in withdrawal of care and discharge to nursing home. Patient 3 was a 50-year-old black female whose serum GAD-Ab titre was 0.08 mmol/l, and was discovered to have pulmonary sarcoidosis. Treatment with steroids and intravenous immunoglobulin resulted in seizure resolution. Due to the responsiveness to immunotherapy, there may be an association between GAD-Abs and refractory seizures, including refractory status epilepticus. Causation cannot be established since GAD-Abs may be elevated secondary to concurrent autoimmune diseases or formed de novo in response to GAD antigen exposure by neuronal injury. Based on this report and available literature, there may be a role for immuno- and chemotherapy in the management of refractory status epilepticus associated with GAD-Abs. PMID- 26878121 TI - Bilateral posterior semi-circular canal obliteration surgery for refractory benign paroxysmal positional vertigo (BPPV) in three patients. PMID- 26878122 TI - The protective effect of epicatechin on experimental ulcerative colitis in mice is mediated by increasing antioxidation and by the inhibition of NF-kappaB pathway. AB - BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory intestinal disease. It is necessary to find out new effective drugs for UC. In our study epicatechin extracted from grape seed by our institute for the first time could treat UC effectively. Then anti-UC mechanisms of epicatechin were elucidated in vivo and in vitro. METHODS: Dextran sulfate sodium (DSS)-induced acute UC mice model was used to evaluate the activity of epicatechin and its properties against UC. Then its anti-inflammatory and antioxidant effects were evaluated as follows: the concentrations of TNF-alpha and IL-6 in the colon supernatants were determined by ELISA. NO and MPO were assayed by Griess method and commercial kit respectively. NF-kappaB were determined by NF-kappaB-Dependent Reporter Gene Expression Assay and Western Blotting respectively. Antioxidant factors such as SOD, MDA, GSH-Px and CAT were also measured in colon tissues and cell supernatant stimulated by LPS respectively. RESULTS: In C57BL/6J mice model with DSS-induced UC, epicatechin was able to decrease the disease activity index and colon macroscopic damage index scores, reduce body weight loss, and significantly relieve colon contracture and crypt damage. TNF-alpha, IL-6, NO, MPO and MDA were reduced in the mice administered epicatechin, whereas antioxidant enzymes showed increased activity in epicatechin-treated mice and cell line respectively. Furthermore, inhibition effect on NF-kappaB activation by epicatechin were demonstrated in vivo and in vitro. CONCLUSIONS: Epicatechin has inhibitory effect on DSS-induced acute UC. This effect is mainly due to its antioxidant effect and the inhibition of inflammatory molecules related to NF-kappaB pathway. PMID- 26878123 TI - Oral biomarkers in exercise-induced neuroplasticity in Parkinson's disease. AB - In this article, we review candidate biomarkers for Parkinson's disease (PD) in oral cavity, potential of oral biomarkers as markers of neuroplasticity, and literature on the effects of exercise on oral cavity biomarkers in PD. We first describe how pathophysiological pathways of PD may be transduced from brain stem and ganglia to oral cavity through the autonomic nervous system or transduced by a reverse path. Next we describe the effects of exercise in PD and potential impact on oral cavity. We propose that biomarkers in oral cavity may be useful targets for describing exercise-induced brain neuroplasticity in PD. Nevertheless, much research remains to be carried out before applying these biomarkers for the determination of disease state and therapeutic response to develop strategies to mitigate motor or non-motor symptoms in PD. PMID- 26878124 TI - A multilevel ant colony optimization algorithm for classical and isothermic DNA sequencing by hybridization with multiplicity information available. AB - The classical sequencing by hybridization takes into account a binary information about sequence composition. A given element from an oligonucleotide library is or is not a part of the target sequence. However, the DNA chip technology has been developed and it enables to receive a partial information about multiplicity of each oligonucleotide the analyzed sequence consist of. Currently, it is not possible to assess the exact data of such type but even partial information should be very useful. Two realistic multiplicity information models are taken into consideration in this paper. The first one, called "one and many" assumes that it is possible to obtain information if a given oligonucleotide occurs in a reconstructed sequence once or more than once. According to the second model, called "one, two and many", one is able to receive from biochemical experiment information if a given oligonucleotide is present in an analyzed sequence once, twice or at least three times. An ant colony optimization algorithm has been implemented to verify the above models and to compare with existing algorithms for sequencing by hybridization which utilize the additional information. The proposed algorithm solves the problem with any kind of hybridization errors. Computational experiment results confirm that using even the partial information about multiplicity leads to increased quality of reconstructed sequences. Moreover, they also show that the more precise model enables to obtain better solutions and the ant colony optimization algorithm outperforms the existing ones. Test data sets and the proposed ant colony optimization algorithm are available on: http://bioserver.cs.put.poznan.pl/download/ACO4mSBH.zip. PMID- 26878125 TI - On origin and evolution of carbonic anhydrase isozymes: A phylogenetic analysis from whole-enzyme to active site. AB - Genetic evolution of carbonic anhydrase enzyme provides an interesting instance of functional similarity in spite of structural diversity of the members of a given family of enzymes. Phylogenetic analysis of alpha-, beta- and gamma carbonic anhydrase was carried out to determine the evolutionary relationships among various members of the family with the enzyme marking its presence in a wide range of cellular and chromosomal locations. The presence of more than one class of enzymes in a particular organism was revealed by phylogenetic time tree. The evolutionary relationships among the members of animal, plant and microbial kingdom were developed. The study revises a long-established notion of kingdom specificity of the different classes of carbonic anhydrases and provides a new version of the presence of multiple classes of carbonic anhydrases in a single organism and the presence of a given class of carbonic anhydrase across different kingdoms. PMID- 26878126 TI - Model-guided metabolic gene knockout of gnd for enhanced succinate production in Escherichia coli from glucose and glycerol substrates. AB - The metabolic role of 6-phosphogluconate dehydrogenase (gnd) under anaerobic conditions with respect to succinate production in Escherichia coli remained largely unspecified. Herein we report what are to our knowledge the first metabolic gene knockout of gnd to have increased succinic acid production using both glucose and glycerol substrates in E. coli. Guided by a genome scale metabolic model, we engineered the E. coli host metabolism to enhance anaerobic production of succinic acid by deleting the gnd gene, considering its location in the boundary of oxidative and non-oxidative pentose phosphate pathway. This strategy induced either the activation of malic enzyme, causing up-regulation of phosphoenolpyruvate carboxylase (ppc) and down regulation of phosphoenolpyruvate carboxykinase (ppck) and/or prevents the decarboxylation of 6 phosphogluconate to increase the pool of glyceraldehyde-3-phosphate (GAP) that is required for the formation of phosphoenolpyruvate (PEP). This approach produced a mutant strain BMS2 with succinic acid production titers of 0.35 g l(-1) and 1.40 g l(-1) from glucose and glycerol substrates respectively. This work further clearly elucidates and informs other studies that the gnd gene, is a novel deletion target for increasing succinate production in E. coli under anaerobic condition using glucose and glycerol carbon sources. The knowledge gained in this study would help in E. coli and other microbial strains development for increasing succinate production and/or other industrial chemicals. PMID- 26878127 TI - Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent. AB - In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)] 1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 MUM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460MUM cell lines respectively] possess promising cytotoxic activity. PMID- 26878128 TI - Carcinogenicity prediction of noncongeneric chemicals by augmented top priority fragment classification. AB - Carcinogenicity prediction is an important process that can be performed to cut down experimental costs and save animal lives. The current reliability of the results is however disputed. Here, a blind exercise in carcinogenicity category assessment is performed using augmented top priority fragment classification. The procedure analyses the applicability domain of the dataset, allocates in clusters the compounds using a leading molecular fragment, and a similarity measure. The exercise is applied to three compound datasets derived from the Lois Gold Carcinogenic Database. The results, showing good agreement with experimental data, are compared with published ones. A final discussion on our viewpoint on the possibilities that the carcinogenicity modelling of chemical compounds offers is presented. PMID- 26878129 TI - In silico characterization of the interaction between LSKL peptide, a LAP-TGF beta derived peptide, and ADAMTS1. AB - Metalloproteases involved in extracellular matrix remodeling play a pivotal role in cell response by regulating the bioavailability of cytokines and growth factors. Recently, the disintegrin and metalloprotease, ADAMTS1 has been demonstrated to be able to activate the transforming growth factor TGF-beta, a major factor in fibrosis and cancer. The KTFR sequence from ADAMTS1 is responsible for the interaction with the LSKL peptide from the latent form of TGF beta, leading to its activation. While the atomic details of the interaction site can be the basis of the rational design of efficient inhibitory molecules, the binding mode of interaction is totally unknown. In this study, we show that recombinant fragments of human ADAMTS1 containing KTFR sequence keep the ability to bind the latent form of TGF-beta. The recombinant fragment with the best affinity is modeled to investigate the binding mode of LSKL peptide with ADAMTS1 at the atomic level. Using a combined approach with molecular docking and multiple independent molecular dynamics (MD) simulations, we provide the binding mode of LSKL peptide with ADAMTS1. The MD simulations starting with the two lowest energy model predicted by molecular docking shows stable interactions characterized by 3 salt bridges (K3-NH3(+) with E626-COO(-); L4-COO(-) with K619 NH3(+); L1-NH3(+) with E624-COO(-)) and 2 hydrogen bonds (S2-OH with E623-COO(-); L4-NH with E623-COO(-)). The knowledge of this interaction mechanism paves the way to the design of more potent and more specific inhibitors against the inappropriate activation of TGF-beta by ADAMTS1 in liver diseases. PMID- 26878130 TI - Guided macro-mutation in a graded energy based genetic algorithm for protein structure prediction. AB - Protein structure prediction is considered as one of the most challenging and computationally intractable combinatorial problem. Thus, the efficient modeling of convoluted search space, the clever use of energy functions, and more importantly, the use of effective sampling algorithms become crucial to address this problem. For protein structure modeling, an off-lattice model provides limited scopes to exercise and evaluate the algorithmic developments due to its astronomically large set of data-points. In contrast, an on-lattice model widens the scopes and permits studying the relatively larger proteins because of its finite set of data-points. In this work, we took the full advantage of an on lattice model by using a face-centered-cube lattice that has the highest packing density with the maximum degree of freedom. We proposed a graded energy strategically mixes the Miyazawa-Jernigan (MJ) energy with the hydrophobic-polar (HP) energy-based genetic algorithm (GA) for conformational search. In our application, we introduced a 2 * 2 HP energy guided macro-mutation operator within the GA to explore the best possible local changes exhaustively. Conversely, the 20 * 20 MJ energy model-the ultimate objective function of our GA that needs to be minimized-considers the impacts amongst the 20 different amino acids and allow searching the globally acceptable conformations. On a set of benchmark proteins, our proposed approach outperformed state-of-the-art approaches in terms of the free energy levels and the root-mean-square deviations. PMID- 26878132 TI - Distinctive properties of plaque-type dura mater graft-associated Creutzfeldt Jakob disease in cell-protein misfolding cyclic amplification. AB - There are two distinct subtypes of dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) with methionine homozygosity at codon 129 of the PRNP gene. The majority of cases is represented by a non-plaque-type (np-dCJD) resembling sporadic CJD (sCJD)-MM1 or -MV1, while the minority by a plaque-type (p-dCJD). p dCJD shows distinctive phenotypic features, namely numerous kuru plaques and an abnormal isoform of prion protein (PrP(Sc)) intermediate in size between types 1 and 2. Transmission studies have shown that the unusual phenotypic features of p dCJD are linked to the V2 prion strain that is associated with sCJD subtypes VV2 or -MV2. In this study, we applied protein misfolding cyclic amplification (PMCA) using recombinant human prion protein as a substrate and demonstrated that p-dCJD prions show amplification features that are distinct from those of np-dCJD. Although no amplification of np-dCJD prions was observed with either 129 M or 129 V substrate, p-dCJD prions were drastically amplified with the 129 V substrates, despite the PRNP codon 129 incompatibility between seed and substrate. Moreover, by using a type 2 PrP(Sc)-specific antibody not recognizing PrP(Sc) in p-dCJD, we found that type 2 products are generated de novo from p-dCJD prions during PMCA with the 129 V substrates. These findings suggest that our cell-PMCA is a useful tool for easily and rapidly identifying acquired CJD associated with the transmission of the V2 CJD strain to codon 129 methionine homozygotes, based on the preference for the 129 V substrate and the type of the amplified products. PMID- 26878131 TI - ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells. AB - Lung epithelial apoptosis and inflammatory responses are important pathological processes in many pulmonary disorders. ResolvinD1 (RvD1), generated in inflammatory resolution processes, reduces inflammatory responses in animal models of lung diseases. The aim of this study was to investigate whether RvD1 attenuates apoptosis and proinflammatory responses in primary human alveolar epithelial type 2 cells (AEC2 cells) that are exposed to lipopolysaccharide (LPS) in vitro. We examined the percentage of apoptotic AEC2 cells by flow cytometry. The expression levels of cytokines and chemokines were determined by ELISA and microarray. The expression levels of molecular signaling modulators were evaluated by western blot. LPS-stimulated AEC2 cells pretreated with RvD1 exhibited a statistically significant reduction in apoptosis. The pretreatment of LPS-stimulated cells with RvD1 stimulated the phosphorylation of AKT and prevented the cleavage of caspase-3, the upregulation of Bax, and the downregulation of Bcl-2. The antiapoptotic effects of RvD1 were abrogated upon pretreatment with a PI3K inhibitor. In addition, RvD1 reduced the release of cytokines and chemokines, and inhibited the degradation and phosphorylation of IkappaB-alpha in LPS-stimulated AEC2 cells. RvD1 reduces apoptosis of LPS-exposed AEC2 cells by inducing the phosphorylation of AKT and attenuates the inflammatory response by suppressing the degradation and phosphorylation of IkappaB-alpha. PMID- 26878133 TI - A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas. AB - Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes. PMID- 26878134 TI - Requirement of CXCL12-CXCR7 signaling for CD20(-) CD138(-) double-negative population in lymphoplasmacytic lymphoma. AB - Cancer cells with tumorigenic potential are limited to a small subpopulation known as cancer-initiating cells (CICs). Recently we investigated a candidate of CICs of lymphoplasmacytic lymphoma (LPL), which is positive for both B-cell marker CD20 and plasma-cell marker CD138. We reported that the subpopulation of CD20(-) CD138(-) phenotype, in which both markers were negative was a candidate of CICs in LPL using LPL cell line, MWCL-1. CICs are known to be plastic under stressed condition, in which non-CICs are changed to CICs. In the present study, we investigated the plasticity of CICs of LPL, and found that hypoxia induced the conversion of CD20(+) CD138(-) to CD20(-) CD138(-) phenotype. We then searched for markers preferentially expressed in CD20(-) CD138(-) subpopulation, and the chemokine receptor CXCR7 was isolated. When cultured with CXCL12, a ligand of CXCR7, the number of CD20(-) CD138(-) cells increased in a time- and dose dependent manner. In addition, hypoxia enhanced the expression level of CXCL12 in MWCL-1. In clinical samples of LPL, a few tumor cells expressed CXCR7, in which CD20 expression was not detected. These results indicated that hypoxia and CXCL12 CXCR7 axis appeared to be advantageous microenvironments to CD20(-) CD138(-) cells. PMID- 26878135 TI - DA-1229, a dipeptidyl peptidase IV inhibitor, protects against renal injury by preventing podocyte damage in an animal model of progressive renal injury. AB - Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls. Although DA-1229 did not affect glycemic control or insulin resistance, DA-1229 did improve lipid profiles, albuminuria and renal fibrosis. Moreover, DA-1229 treatment resulted in decreased urinary excretion of nephrin, decreased circulating and kidney DPPIV activity, and decreased macrophage infiltration in the kidney. In adriamycin-treated mice, DPPIV activity in the kidney and urinary nephrin loss were both increased, whereas glucagon-like peptide-1 concentrations were unchanged. Moreover, DA-1229 treatment significantly improved proteinuria, renal fibrosis and inflammation associated with decreased urinary nephrin loss, and kidney DPP4 activity. In cultured podocytes, DA-1229 restored the high glucose/angiotensin II-induced increase of DPPIV activity and preserved the nephrin levels in podocytes. These findings suggest that activation of DPPIV in the kidney has a role in the progression of renal disease, and that DA-1229 may exert its renoprotective effects by preventing podocyte injury. PMID- 26878137 TI - NSCLC tumor shrinkage prediction using quantitative image features. AB - The objective of this study was to develop a quantitative image feature model to predict non-small cell lung cancer (NSCLC) volume shrinkage from pre-treatment CT images. 64 stage II-IIIB NSCLC patients with similar treatments were all imaged using the same CT scanner and protocol. For each patient, the planning gross tumor volume (GTV) was deformed onto the week 6 treatment image, and tumor shrinkage was quantified as the deformed GTV volume divided by the planning GTV volume. Geometric, intensity histogram, absolute gradient image, co-occurrence matrix, and run-length matrix image features were extracted from each planning GTV. Prediction models were generated using principal component regression with simulated annealing subset selection. Performance was quantified using the mean squared error (MSE) between the predicted and observed tumor shrinkages. Permutation tests were used to validate the results. The optimal prediction model gave a strong correlation between the observed and predicted tumor shrinkages with r=0.81 and MSE=8.60*10(-3). Compared to predictions based on the mean population shrinkage this resulted in a 2.92 fold reduction in MSE. In conclusion, this study indicated that quantitative image features extracted from existing pre-treatment CT images can successfully predict tumor shrinkage and provide additional information for clinical decisions regarding patient risk stratification, treatment, and prognosis. PMID- 26878139 TI - Lateral heat flow distribution and defect-dependent thermal resistance in an individual silicon nanowire. AB - Studies aiming to significantly improve thermal properties, such as figure-of merit, of silicon nanowires (SiNW) have focused on diameter reduction and surface or interface roughness control. However, the mechanism underlying thermal conductivity enhancement of roughness controlled NWs remains unclear. Here, we report a significant influence of stacking faults (SFs) on the lateral thermal conductivity of a single SiNW, using a combination of newly developed in situ spatially-resolved thermal resistance experiments and high-resolution transmission electron microscopy measurements. We used as-grown SiNWs tapered along the growth direction with progressively lower roughness and SFs density. The results clearly confirmed that both surface roughness and twins or SFs densities suppress the thermal conductivity of an individual SiNW. The results and measurement techniques presented here hold great potential for inspecting minute changes in thermal resistance along an individual SiNW, caused by induced SFs on the nanostructure, and for improving one-dimensional nanowire-based thermoelectric device performance. PMID- 26878138 TI - A multi-center milestone study of clinical vertebral CT segmentation. AB - A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention. PMID- 26878140 TI - Strength of recommendation for single-visit root canal treatment: grading the body of the evidence using a patient-centred approach. AB - AIM: To identify, search for and critically interpret the results from clinical studies on single- versus multiple-visit root canal treatment in the light of an evidence-based paradigm. For that purpose, the quality of the available body of evidence was assessed using the SORT 'grade' - Strength of Recommendation Taxonomy. METHODOLOGY: A protocol was followed including all aspects of the review methods: (i) search strategy, (ii) inclusion criteria for studies, (iii) screening methods, (iv) quality assessment, (v) data synthesis of the selected studies, and (vi) the assessment of quality of the body of evidence available by the means of the SORT 'grade'. An extensive search of recent biomedical literature was performed in PubMed (up to May, 2014), EMBASE (dating from 1980 to May 2014) and Cochrane databases with appropriate headings and keywords related to single- and multiple-visit root canal treatment. Selected studies were stratified according to their level of evidence using the SORT criteria: (i) quality - Level A high-quality evidence, Level B medium/low-quality evidence and Level C no evidence; (ii) degree of consistency - consistent, when most studies found a similar conclusion, or inconsistent, when there was considerable variation amongst study findings. RESULTS: After the digital and manual searches, 246 studies were indentified. Two hundred and seven studies were eliminated by exclusion criteria, resulting in a yield of 39 articles that were selected for retrieval. Of the 39 articles, only 11 could be classified as Level 2 (B); the other 28 articles did not obey the criteria to be considered as real patient oriented evidence; thus, they were classified as Level 3 (C). No studies were ranked as Level 1 because they did not obey the minimum standard to be considered as both good-quality research and patient-oriented evidence. Despite this, all of the selected Level B studies reported no significant differences between single- and multiple-visit treatments. CONCLUSION: There is B-level (mid-level) evidence to confirm there is no difference between the two different treatments, based on research addressing clinical outcomes and using some consistent but limited quality methods of scientific investigation. More studies focused on evaluating patient-centred outcomes are urgently required. PMID- 26878141 TI - Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. AB - The current gold standard to reduce non-specific cellular uptake of drug delivery vehicles is by covalent attachment of poly(ethylene glycol) (PEG). It is thought that PEG can reduce protein adsorption and thereby confer a stealth effect. Here, we show that polystyrene nanocarriers that have been modified with PEG or poly(ethyl ethylene phosphate) (PEEP) and exposed to plasma proteins exhibit a low cellular uptake, whereas those not exposed to plasma proteins show high non specific uptake. Mass spectrometric analysis revealed that exposed nanocarriers formed a protein corona that contains an abundance of clusterin proteins (also known as apolipoprotein J). When the polymer-modified nanocarriers were incubated with clusterin, non-specific cellular uptake could be reduced. Our results show that in addition to reducing protein adsorption, PEG, and now PEEPs, can affect the composition of the protein corona that forms around nanocarriers, and the presence of distinct proteins is necessary to prevent non-specific cellular uptake. PMID- 26878142 TI - Intraoperative diagnostics and elimination of residual microtumours with plasmonic nanobubbles. AB - Failure of cancer surgery to intraoperatively detect and eliminate microscopic residual disease (MRD) causes lethal recurrence and metastases, and the removal of important normal tissues causes excessive morbidity. Here, we show that a plasmonic nanobubble (PNB), a non-stationary laser pulse-activated nanoevent, intraoperatively detects and eliminates MRD in the surgical bed. PNBs were generated in vivo in head and neck cancer cells by systemically targeting tumours with gold colloids and locally applying near-infrared, low-energy short laser pulses, and were simultaneously detected with an acoustic probe. In mouse models, between 3 and 30 residual cancer cells and MRD (undetectable with current methods) were non-invasively detected up to 4 mm deep in the surgical bed within 1 ms. In resectable MRD, PNB-guided surgery prevented local recurrence and delivered 100% tumour-free survival. In unresectable MRD, PNB nanosurgery improved survival twofold compared with standard surgery. Our results show that PNB-guided surgery and nanosurgery can rapidly and precisely detect and remove MRD in simple intraoperative procedures. PMID- 26878144 TI - Drug delivery: Redefining tumour vascular barriers. PMID- 26878143 TI - Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery. AB - Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named 'eruptions') into the tumour interstitial space. We propose that 'dynamic vents' form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug. PMID- 26878145 TI - Drug delivery: Unravelling the stealth effect. PMID- 26878146 TI - An electronic aromaticity index for large rings. AB - We introduce a new electronic aromaticity index, AV1245, consisting of an average of the 4-center multicenter indices (MCI) along the ring that keeps a positional relationship of 1, 2, 4, 5. AV1245 measures the extent of transferability of the delocalized electrons between bonds 1-2 and 4-5, which is expected to be large in conjugated circuits and, therefore, in aromatic molecules. A new algorithm for the calculation of MCI for large rings is also introduced and used to produce the data for the calibration of the new aromaticity index. AV1245 does not rely on reference values, does not suffer from large numerical precision errors, and it does not present any limitation on the nature of atoms, the molecular geometry or the level of calculation. It is a size-extensive measure with low computational cost that grows linearly with the number of ring members. Therefore, it is especially suitable to study the aromaticity of large molecular rings such as those occurring in belt-shaped Mobius structures or porphyrins. The analysis of AV1245 in free-base and bis-metalated Pd [32]octaphyrins(1,0,1,0,1,0,1,0) completes this study. PMID- 26878148 TI - FeCl3-Mediated One-Pot Domino Reactions for the Synthesis of 9-Aryl/9-Arylethynyl 2,3,4,9-tetrahydro-1H-xanthen-1-ones from Propargylic Amines/Diaryl Amines and 1,3-Cyclohexanediones. AB - An efficient, environmentally friendly and one-pot route to new 9-aryl/9 arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-one derivatives from inexpensive starting materials has been developed. This method proceeded by a domino nucleophilic-substitution/intramolecular cyclization/dehydration sequence of propargylic amines/diaryl amines and 1,3-cyclohexanediones under the promotion of FeCl3, which involved the formation of two new sigma (C-C and C-O) bonds in a single operation for the construction of novel tetrahydroxanthene skeletons in 68 95% yields. PMID- 26878149 TI - Palladium-Catalyzed Arylation of Aryl Sulfenate Anions with Aryl Bromides under Mild Conditions: Synthesis of Diaryl Sulfoxides. AB - A palladium-catalyzed arylation of aryl sulfenate anions generated from aryl 2 (trimethylsilyl)ethyl sulfoxides and CsF has been developed. This protocol is effective for the synthesis of diaryl sulfoxides and heteroaryl aryl sulfoxides under mild conditions employing aryl bromides. Various functional groups, including those with acidic protons, are well tolerated. PMID- 26878147 TI - Mechanism of Glycosylation of Anomeric Sulfonium Ions. AB - Anomeric sulfonium ions are attractive glycosyl donors for the stereoselective installation of 1,2-cis glycosides. Although these donors are receiving increasing attention, their mechanism of glycosylation remains controversial. We have investigated the reaction mechanism of glycosylation of a donor modified at C-2 with a (1S)-phenyl-2-(phenylsulfanyl)ethyl chiral auxiliary. Preactivation of this donor results in the formation of a bicyclic beta-sulfonium ion that after addition of an alcohol undergoes 1,2-cis-glycosylation. To probe the importance of the thiophenyl moiety, analogs were prepared in which this moiety was replaced by an anisoyl or benzyl moiety. Furthermore, the auxiliaries were installed as S- and R-stereoisomers. It was found that the nature of the heteroatom and chirality of the auxiliary greatly influenced the anomeric outcome and only the one containing a thiophenyl moiety and having S-configuration gave consistently alpha anomeric products. The sulfonium ions are sufficiently stable at a temperature at which glycosylations proceed indicating that they are viable glycosylation agents. Time-course NMR experiments with the latter donor showed that the initial rates of glycosylations increase with increases in acceptor concentration and the rate curves could be fitted to a second order rate equation. Collectively, these observations support a mechanism by which a sulfonium ion intermediate is formed as a trans-decalin ring system that can undergo glycosylation through a bimolecular mechanism. DFT calculations have provided further insight into the reaction path of glycosylation and indicate that initially a hydrogen-bonded complex is formed between sulfonium ion and acceptor that undergoes SN2-like glycosylation to give an alpha-anomeric product. PMID- 26878151 TI - Tuning of Stepwise Neutral-Ionic Transitions by Acceptor Site Doping in Alternating Donor/Acceptor Chains. AB - The stepwise neutral-ionic (N-I) phase transition found in the alternating donor/acceptor (DA) chain [Ru2(2,3,5,6-F4PhCO2)4(DMDCNQI)].2(p-xylene) (0; 2,3,5,6-F4PhCO2(-) = 2,3,5,6-tetrafluorobenzoate; DMDCNQI = 2,5-dimethyl-N,N' dicyanoquinonediimine) was tuned by partly substituting the acceptor DMDCNQI with 2,5-dimethoxy-N,N'-dicyanoquinonediimine (DMeODCNQI), which displays a poorer electron affinity in an isostructural series. The site-doped series comprised [Ru2(2,3,5,6-F4PhCO2)4(DMDCNQI)1-x(DMeODCNQI)x].2(p-xylene) for doping rates (x) = 0.05 (0.05-MeO), 0.10 (0.10-MeO), 0.15 (0.15-MeO), and 0.20 (0.20-MeO). The neutral chain [Ru2(2,3,5,6-F4PhCO2)4(DMeODCNQI)].4(p-xylene) (1), which only contained DMeODCNQI, was also characterized. All site-doped compounds were isostructural to 0 except 1 despite their identical DA chain motif. Except at an x value of 0.20, they displayed a two-step N-I transition involving an intermediate phase. This transition occurred at high temperatures in 0 but shifted to lower temperatures in a parallel manner with increasing doping rate. Simultaneously, each transition broadened with increasing doping rate, leading to a convergence of two transitions at an x value approximating 0.2. Donor/acceptor site-doping techniques present somewhat different impacts in terms of interchain Coulomb effects. PMID- 26878150 TI - A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing. AB - A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 MUM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 MUM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 MUM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed. PMID- 26878153 TI - Co-Cu Nanoparticles: Synthesis by Galvanic Replacement and Phase Rearrangement during Catalytic Activation. AB - The control of the phase distribution in multicomponent nanomaterials is critical to optimize their catalytic performance. In this direction, while impressive advances have been achieved in the past decade in the synthesis of multicomponent nanoparticles and nanocomposites, element rearrangement during catalyst activation has been frequently overseen. Here, we present a facile galvanic replacement-based procedure to synthesize Co@Cu nanoparticles with narrow size and composition distributions. We further characterize their phase arrangement before and after catalytic activation. When oxidized at 350 degrees C in air to remove organics, Co@Cu core-shell nanostructures oxidize to polycrystalline CuO Co3O4 nanoparticles with randomly distributed CuO and Co3O4 crystallites. During a posterior reduction treatment in H2 atmosphere, Cu precipitates in a metallic core and Co migrates to the nanoparticle surface to form Cu@Co core-shell nanostructures. The catalytic behavior of such Cu@Co nanoparticles supported on mesoporous silica was further analyzed toward CO2 hydrogenation in real working conditions. PMID- 26878152 TI - Hybrid Organic-Inorganic Perovskites on the Move. AB - Hybrid organic-inorganic perovskites (HOIPs) are crystals with the structural formula ABX3, where A, B, and X are organic and inorganic ions, respectively. While known for several decades, HOIPs have only in recent years emerged as extremely promising semiconducting materials for solar energy applications. In particular, power-conversion efficiencies of HOIP-based solar cells have improved at a record speed and, after only little more than 6 years of photovoltaics research, surpassed the 20% threshold, which is an outstanding result for a solution-processable material. It is thus of fundamental importance to reveal physical and chemical phenomena that contribute to, or limit, these impressive photovoltaic efficiencies. To understand charge-transport and light-absorption properties of semiconducting materials, one often invokes a lattice of ions displaced from their static positions only by harmonic vibrations. However, a preponderance of recent studies suggests that this picture is not sufficient for HOIPs, where a variety of structurally dynamic effects, beyond small harmonic vibrations, arises already at room temperature. In this Account, we focus on these effects. First, we review structure and bonding in HOIPs and relate them to the promising charge-transport and absorption properties of these materials, in terms of favorable electronic properties. We point out that HOIPs are much "softer" mechanically, compared to other efficient solar-cell materials, and that this can result in large ionic displacements at room temperature. We therefore focus next on dynamic structural effects in HOIPs, going beyond a static band structure picture. Specifically, we discuss pertinent experimental and theoretical findings as to phase-transition behavior and molecular/octahedral rearrangements. We then discuss atomic diffusion phenomena in HOIPs, with an emphasis on the migration of intrinsic and extrinsic ionic species. From this combined perspective, HOIPs appear as highly dynamic materials, in which structural fluctuations and long-range ionic motion have an unusually strong impact on charge-transport and optical properties. We highlight the potential implications of these effects for several intriguing phenomenological observations, ranging from scattering mechanisms and lifetimes of charge carriers to light-induced structural effects and ionic conduction. PMID- 26878154 TI - A Method for Designing Instrument-Free Quantitative Immunoassays. AB - Colorimetric readouts are widely used in point-of-care diagnostic immunoassays to indicate either the presence or the absence of an analyte. For a variety of reasons, it is more difficult to quantify rather than simply detect an analyte using a colorimetric test. We report a method for designing, with minimal iteration, a quantitative immunoassay that can be interpreted objectively by a simple count of number of spots visible to the unaided eye. We combined a method called polymerization-based amplification (PBA) with a series of microscale features containing a decreasing surface density of capture molecules, and the central focus of the study is understanding how the choice of surface densities impacts performance. Using a model pair of antibodies, we have shown that our design approach does not depend on measurement of equilibrium and kinetic binding parameters and can provide a dynamic working range of 3 orders of magnitude (70 pM to 70 nM) for visual quantification. PMID- 26878155 TI - Survival improvements associated with access to biological agents: Results from the South Australian (SA) metastatic colorectal cancer (mCRC) registry. AB - Background Randomized controlled trials evaluating biological therapy have shown improvements in survival from metastatic colorectal cancer (mCRC). Subjects in the trials represent a selected proportion of mCRC patients. We have the potential to assess the impact of biological therapy on mCRC outcomes, particularly the effect of bevacizumab, from a population-based clinical registry by comparing two time cohorts with differences in therapy accessibility. Material and methods A retrospective cohort study was performed by analyzing the South Australian (SA) mCRC registry data based on diagnosis in two time periods: 1 February 2006-31 May 2009 (Cohort A) versus 1 June 2009-30 June 2014 (Cohort B). The demarcation for these cohorts was chosen to reflect the change in accessibility of bevacizumab from July 2009. Results Between February 2006 and June 2014, 3308 patients were identified through the SA mCRC registry: 1464 (44%) in Cohort A and 1844 (56%) in Cohort B. 61 and 59% patients in Cohort A and B, respectively received systemic therapy (p = 0.26). Major differences in clinical characteristics were: biological therapy use 18 versus 33% (p < 0.001) and clinical trial enrolment 12 versus 7% (p < 0.001). Uptake of bevacizumab was: first-line 9 versus 42% and second-line 6 versus 16%. Median overall survival (mOS) for the entire group was: 13.1 versus 17.1 months (HR 0.80; 95% CI 0.74 0.87). Evaluation restricted to patients receiving systemic therapy was 20.5 versus 25.2 months (HR 0.80; 95% CI 0.72-0.89). Multivariate analysis indicated that biological therapy and Cohort B were associated with improved mOS. Conclusion The expected rise in bevacizumab administration was observed in Cohort B. Its use in first-line therapy remained relatively low even after the reimbursement, potentially reflecting real world practice where comorbidities, primary in-situ and age may contraindicate its use. mOS improvement over time was attributed to increased access to biological therapy, especially bevacizumab and possibly advance in peri-operative and supportive care. PMID- 26878156 TI - Prognostic significance of modified Glasgow Prognostic Score in patients with non metastatic clear cell renal cell carcinoma. AB - Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p < 0.001), T stage (p = 0.024) and lymphovascular invasion (p = 0.046) were independent prognostic factors for RFS, whereas mGPS (p = 0.001) was the only independent prognostic factor for CSS. Conclusions The mGPS is an independent prognostic factor for RFS and CSS in patients with non-metastatic clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC. PMID- 26878157 TI - Strategies in early clinical development for the treatment of basic defects of cystic fibrosis. AB - INTRODUCTION: Twenty-six years after the identification of the gene responsible for cystic fibrosis (CF), controversies still surround the pathogenesis of the disease that continues to burden and shorten lives. Therefore, finding effective therapeutic strategies that target the basic defect of CF is crucially needed. AREAS COVERED: This review offers a comprehensive survey of fundamental therapies in early stages of development for the treatment of CF. The first part describes recent strategies targeting the basic defect either at the gene or at the transcript level. The second part summarizes a panel of novel strategies targeting protein repair. The third part reports strategies targeting non-CFTR channels. EXPERT OPINION: Recent major breakthroughs in CF therapy have been made, raising hope to find a cure for CF. Apart from Vertex corrector and potentiator molecules (lumacaftor, ivacaftor, VX-661) and from ataluren, used to correct nonsense mutations, most compounds being currently tested are in very early (I-II) phases of development and definitive clinical results are keenly expected. Among the broad list of molecules and strategies being tested, the QR 010 compound and inhibitors of phosphodiesterase type 5 (sildenafil, vardenafil) could reveal a strong potentiality as therapeutic candidates to cure CF. PMID- 26878158 TI - The modulation of disjunctive assertions. AB - The theory of mental models postulates that disjunctions of the sort, A or B, where A and B are sensible everyday clauses, have a core meaning that allows an inclusive interpretation, referring to three possibilities: A and not-B, not-A and B, and A and B. The meaning of the clauses and knowledge can modulate this meaning by blocking the construction of at least one model of a possibility-for example, "Rui is playing tennis or he is surfing" blocks the model of Rui doing both activities. This theory is implemented in a computer program. Three experiments investigated the core interpretation and interpretations in which the contents of the clauses should block the model of A and B (as in the preceding example), the model of A and not-B, or the model of not-A and B. In Experiment 1, the participants listed the possibilities for each of the four sorts of disjunction. The results corroborated the predicted modulations. In Experiment 2, these predicted interpretations governed the conclusions that participants accepted from disjunctions and categorical premises. In Experiment 3, the predicted interpretations yielded reliable effects on the conclusions that the participants drew for themselves. We relate these results to theories of reasoning. PMID- 26878159 TI - Prodrugs for transdermal drug delivery - trends and challenges. AB - Prodrugs continue to attract significant interest in the transdermal drug delivery field. These moieties can confer favorable physicochemical properties on transdermal drug delivery candidates. Alkyl chain lengthening, pegylation are some of the strategies used for prodrug synthesis. It is usually important to optimize partition coefficient, water and oil solubilities of drugs. In this review, progress made in the field of prodrugs for percutaneous penetration is highlighted and the challenges discussed. PMID- 26878160 TI - Simultanagnosia: when all you can see are trees, the forest still rules. AB - We investigated the nature of covertly processed visual elements in a patient with simultanagnosia, a disorder characterized by the inability to perceive multiple aspects of a visual scene all at once. Using the first letter of the color words red, green, or blue, we created a novel testing paradigm that combined Navon global-local stimuli with a single-letter Stroop task. The letters R, G, or B were arranged in the overall configuration of a large R, G, or B. The patient never could report seeing the larger letter, and always could name the smaller letters. But, when asked to name ink color only, and ignore letter identity, the large letter covertly affected responding. That is, when the large letter was the same as the first letter of the ink color, the patient named ink color more quickly and accurately than when the large letter was incongruent with the correct response. Moreover, when the covert global and overt local visual processing conflicted, the global letter always dominated over the local letters, despite the patient's inability to perceive it consciously. These data show that the covert processing of global visual information in simultanagnosia can dominate overt local information, even across different streams of information processing. PMID- 26878161 TI - Assessing ventricular function in preterm infants using tissue Doppler imaging. AB - Tissue Doppler imaging (TDI) is a new echocardiographic technique that directly measures velocities in the myocardium. In adult cardiology, it has been well established that echocardiographic assessment using TDI in patients with heart failure should be essential. Recently, TDI assessment has also been applied in children, infants, fetuses, and preterm infants. In very preterm infants, we serially performed echocardiographic assessment including TDI prospectively, and found that TDI velocities at both the mitral and tricuspid valve annulus changed significantly within the first 24 hours of life. It was suggested that the E/Ea ratio for both ventricles in very preterm infants might be almost stable in the early neonatal period. It is suggested that assessment of ventricular function using TDI in preterm infants might be of great value because it allows assessment of both diastolic ventricular function and right ventricular function. PMID- 26878162 TI - Synthesis and biological evaluation of n-butylphthalide derivatives as anti platelet aggregation agents. AB - New analogues of n-butylphthalide (NBP) bearing various lengths of alkyl and different substitution at the two-position of phthalide were designed and synthesised. Preliminary evaluation and prediction of ACD LogP software indicate that the derivatives display significant improvement in water solubility than NBP does. Further biological analysis showed that NBP analogues specifically inhibit platelet aggregation induced by arachidonic acid but have no effect on that induced by adenosine 5-diphosphate. Especially compounds 1 and 3 were stronger than classical anti-platelet drug, aspirin, and equal potent with NBP, respectively. These findings provide an alternative approach to the development of NBP analogues with anti-platelet aggregation activity with good water solubility for the intervention of ischemic stroke. PMID- 26878163 TI - Predicting three-month and 12-month post-fitting real-world hearing-aid outcome using pre-fitting acceptable noise level (ANL). AB - OBJECTIVE: Determine the extent to which pre-fitting acceptable noise level (ANL), with or without other predictors such as hearing-aid experience, can predict real-world hearing-aid outcomes at three and 12 months post-fitting. DESIGN: ANLs were measured before hearing-aid fitting. Post-fitting outcome was assessed using the international outcome inventory for hearing aids (IOI-HA) and a hearing-aid use questionnaire. Models that predicted outcomes (successful vs. unsuccessful) were built using logistic regression and several machine learning algorithms, and were evaluated using the cross-validation technique. STUDY SAMPLE: A total of 132 adults with hearing impairment. RESULTS: The prediction accuracy of the models ranged from 61% to 68% (IOI-HA) and from 55% to 61% (hearing-aid use questionnaire). The models performed more poorly in predicting 12-month than three-month outcomes. The ANL cutoff between successful and unsuccessful users was higher for experienced (~18 dB) than first-time hearing aid users (~10 dB), indicating that most experienced users will be predicted as successful users regardless of their ANLs. CONCLUSIONS: Pre-fitting ANL is more useful in predicting short-term (three months) hearing-aid outcomes for first time users, as measured by the IOI-HA. The prediction accuracy was lower than the accuracy reported by some previous research that used a cross-sectional design. PMID- 26878164 TI - Neutrophil to lymphocyte ratio (NLR) and cardiovascular diseases: an update. AB - As we know, inflammatory and oxidative stresses have a role in the pathogenesis of cardiovascular disease. This knowledge has triggered many investigations targeted to inflammatory markers. One such example, the neutrophil to lymphocyte ratio (NLR), is an inexpensive and easily accessible inflammatory marker whose role in cardiovascular disease has been studied extensively in the past few years. The neutrophil lymphocyte ratio has been shown to predict cardiac arrhythmias as well as short- and long-term mortality in patients with acute coronary syndromes (ACS). It has correlated well with ACS risk prediction models such as the GRACE and SYNTAX scores. A higher NLR has also been associated with frequent congestive heart failure decompensation and long-term mortality. The neutrophil to lymphocyte ratio also appears to have a prognostic role in patients undergoing transaortic valve replacement and the progression of valvular heart diseases. Despite the science of inflammatory biomarkers having been described decades ago, NLR appears to be enjoying a renaissance as a cost-effective biomarker with immediate clinical predictability and prognostication. PMID- 26878166 TI - Improving visual search in instruction manuals using pictograms. AB - Instruction manuals provide important messages about the proper use of a product. They should communicate in such a way that they facilitate users' searches for specific information. Despite the increasing research interest in visual search, there is a lack of empirical knowledge concerning the role of pictograms in search performance during the browsing of a manual's pages. This study investigates how the inclusion of pictograms improves the search for the target information. Furthermore, it examines whether this search process is influenced by the visual similarity between the pictograms and the searched for information. On the basis of eye-tracking measurements, as objective indicators of the participants' visual attention, it was found that pictograms can be a useful element of search strategy. Another interesting finding was that boldface highlighting is a more effective method for improving user experience in information seeking, rather than the similarity between the pictorial and adjacent textual information. Implications for designing effective user manuals are discussed. Practitioner Summary: Users often view instruction manuals with the aim of finding specific information. We used eye-tracking technology to examine different manual pages in order to improve the user's visual search for target information. The results indicate that the use of pictograms and bold highlighting of relevant information facilitate the search process. PMID- 26878165 TI - Functionalised alginate flow seeding microparticles for use in Particle Image Velocimetry (PIV). AB - Alginate microparticles as flow seeding fulfil all the requirements that are recommended for the velocity measurements in Particle Image Velocimetry (PIV). These spherical microparticles offer the advantage of being environmentally friendly, having excellent seeding properties and they can be produced via a very simple process. In the present study, the performances of alginate microparticles functionalised with a fluorescent dye, Rhodamine B (RhB), for PIV have been studied. The efficacy of fluorescence is appreciated in a number of PIV applications since it can boost the signal-to-noise ratio. Alginate microparticles functionalised with RhB have high emission efficiency, desirable match with fluid density and controlled size. The study of the particles behaviour in strong acid and basic solutions and ammonia is also included. This type of particles can be used for measurements with PIV and Planar Laser Induced Fluorescence (PLIF) simultaneously, including acid-base reactions. PMID- 26878167 TI - Discourses in stroke rehabilitation as they present themselves in current physiotherapy and occupational therapy. AB - Aim This study aims to discuss current perceptions of rehabilitation and how present rehabilitation practice is affected by dominating discourses in Danish society by exploring discourses expressed in official publications and the constructed journal notes of occupational and physiotherapists' practice of stroke rehabilitation. Method The frame of reference is Fairclough's critical discourse analysis. The analysis comprises seven official documents relevant to stroke rehabilitation provided in Danish health services in 2012-2013. Also, notes written by occupational therapists and physiotherapists in medical records of 10 patients with a stroke diagnosis admitted to hospital in 2012. The documents included were read thoroughly. The texts were analyzed deductively, focusing on discursive practice on articulated understandings of rehabilitation, health practice approaches, and social practice. Results The dominating discourses seem to be Western neoliberalism organizational, medical and ethical discourses. The macro level of discourses consisted of political documents addressing rehabilitation nationally. The meso level mainly concerned medical discourses within stroke rehabilitation whereas the micro level represented local medical and ethical discourses. Conclusion The neoliberal discourse supports the medical discourse with strong emphasis on evidence-based interventions. In contrast to ethical discourses, documentation of rehabilitation practice marked more attention being paid to facilitating the patient's independence than to enabling the regaining of meaningful activities and participation. Implications for Rehabilitation Individualized rehabilitation must be organized with flexibility as it is a complex process Critical reflectiveness among health professionals is needed to provide individualized rehabilitation of high quality A broader range of stake holders, including patient organizations, are in demand within health policy making The discourses that construct rehabilitation policy and practices are sometimes in conflict, which may impact on, and impede, the rehabilitation for the individual patient. PMID- 26878168 TI - Health-Related Quality of Life in Children and Adolescents with Cerebral Palsy: A Secondary Analysis of the DISABKIDS Questionnaire in the Field-Study Cerebral Palsy Subgroup. AB - INTRODUCTION: Health-related quality of life (HRQOL) instruments are increasingly being used to evaluate interventions and therapy outcomes in children and adolescents with cerebral palsy (CP). A variety of psychometrically sound and validated generic and disease-specific instruments are available. A third type of instrument, the chronic-generic instrument, pertains to features of HRQOL that are shared by various chronic conditions.The DISABKIDS family of questionnaires consists of a chronic-generic core measure (DCGM-37) and several condition specific modules, among these, a CP module (CPM). The objective of this article was to describe the performance and, specifically, the validity of the DCGM-37 and CPM in children and adolescents with CP. METHODS: Psychometric properties of the DCGM-37 and the CPM are presented. The discriminant validity was assessed compared with generic measures of HRQOL regarding different levels of impairment (physical independence; developmental delay). RESULTS: A total of 86 patients with CP (mean age 13 years, range 7-19 years) and 78 main caretakers participated in this study. The DCGM-37 and CPM showed much better discriminative ability as compared with generic questionnaires. CONCLUSIONS: The DCGM-37 and CPM were able to differentiate between patients with different levels of impairment and can be recommended for treatment evaluation and group comparison in clinical studies of children and adolescents with CP. PMID- 26878169 TI - [The 6th International Conference on snakebites and scorpion stings envenoming in Africa: a crucial step for the management of envenoming]. PMID- 26878170 TI - Measles virus nucleocapsid protein increases osteoblast differentiation in Paget's disease. AB - Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption and formation; therefore, PD offers key insights into mechanisms that couple bone resorption and formation. Here, we evaluated OCLs from 3 patients with PD and determined that measles virus nucleocapsid protein (MVNP) was expressed in 70% of these OCLs. Moreover, transgenic mice with OCL-specific expression of MVNP (MVNP mice) developed PD-like bone lesions that required MVNP dependent induction of high IL-6 expression levels in OCLs. In contrast, mice harboring a knockin of p62P394L (p62-KI mice), which is the most frequent PD associated mutation, exhibited increased bone resorption, but not formation. Evaluation of OCLs from MVNP, p62-KI, and WT mice revealed increased IGF1 expression in MVNP-expressing OCLs that resulted from the high IL-6 expression levels in these cells. IL-6, in turn, increased the expression of coupling factors, specifically ephrinB2 on OCLs and EphB4 on osteoblasts (OBs). IGF1 enhanced ephrinB2 expression on OCLs and OB differentiation. Importantly, ephrinB2 and IGF1 levels were increased in MVNP-expressing OCLs from patients with PD and MVNP-transduced human OCLs compared with levels detected in controls. Further, anti-IGF1 or anti-IGF1R blocked Runx2 and osteocalcin upregulation in OBs cocultured with MVNP-expressing OCLs. These results suggest that in PD, MVNP upregulates IL-6 and IGF1 in OCLs to increase ephrinB2-EphB4 coupling and bone formation. PMID- 26878171 TI - FGF23 signaling impairs neutrophil recruitment and host defense during CKD. AB - Chronic kidney disease (CKD) has been associated with impaired host response and increased susceptibility to infections. Leukocyte recruitment during inflammation must be tightly regulated to protect the host against pathogens. FGF23 levels are increased in blood during CKD, and levels of this hormone have been associated with a variety of adverse effects in CKD patients. Here, we have shown that CKD impairs leukocyte recruitment into inflamed tissue and host defense in mice and humans. FGF23 neutralization during CKD in murine models restored leukocyte recruitment and host defense. Intravital microscopy of animals with chronic kidney failure showed that FGF23 inhibits chemokine-activated leukocyte arrest on the endothelium, and downregulation of FGF receptor 2 (FGFR2) on PMNs rescued host defense in these mice. In vitro, FGF23 inhibited PMN adhesion, arrest under flow, and transendothelial migration. Mechanistically, FGF23 binding to FGFR2 counteracted selectin- and chemokine-triggered beta2 integrin activation on PMNs by activating protein kinase A (PKA) and inhibiting activation of the small GTPase Rap1. Moreover, knockdown of PKA abolished the inhibitory effect of FGF23 on integrin activation. Together, our data reveal that FGF23 acts directly on PMNs and dampens host defense by direct interference with chemokine signaling and integrin activation. PMID- 26878172 TI - Blocking mitochondrial calcium release in Schwann cells prevents demyelinating neuropathies. AB - Schwann cells produce myelin sheath around peripheral nerve axons. Myelination is critical for rapid propagation of action potentials, as illustrated by the large number of acquired and hereditary peripheral neuropathies, such as diabetic neuropathy or Charcot-Marie-Tooth diseases, that are commonly associated with a process of demyelination. However, the early molecular events that trigger the demyelination program in these diseases remain unknown. Here, we used virally delivered fluorescent probes and in vivo time-lapse imaging in a mouse model of demyelination to investigate the underlying mechanisms of the demyelination process. We demonstrated that mitochondrial calcium released by voltage-dependent anion channel 1 (VDAC1) after sciatic nerve injury triggers Schwann cell demyelination via ERK1/2, p38, JNK, and c-JUN activation. In diabetic mice, VDAC1 activity was altered, resulting in a mitochondrial calcium leak in Schwann cell cytoplasm, thereby priming the cell for demyelination. Moreover, reduction of mitochondrial calcium release, either by shRNA-mediated VDAC1 silencing or pharmacological inhibition, prevented demyelination, leading to nerve conduction and neuromuscular performance recovery in rodent models of diabetic neuropathy and Charcot-Marie-Tooth diseases. Therefore, this study identifies mitochondria as the early key factor in the molecular mechanism of peripheral demyelination and opens a potential opportunity for the treatment of demyelinating peripheral neuropathies. PMID- 26878174 TI - Heterogeneity of leukemia-initiating capacity of chronic myelogenous leukemia stem cells. AB - Chronic myelogenous leukemia (CML) results from transformation of a long-term hematopoietic stem cell (LTHSC) by expression of the BCR-ABL fusion gene. However, BCR-ABL-expressing LTHSCs are heterogeneous in their capacity as leukemic stem cells (LSCs). Although discrepancies in proliferative, self renewal, and differentiation properties of normal LTHSCs are being increasingly recognized, the mechanisms underlying heterogeneity of leukemic LTHSCs are poorly understood. Using a CML mouse model, we identified gene expression differences between leukemic and nonleukemic LTHSCs. Expression of the thrombopoietin (THPO) receptor MPL was elevated in leukemic LTHSC populations. Compared with LTHSCs with low MPL expression, LTHSCs with high MPL expression showed enhanced JAK/STAT signaling and proliferation in response to THPO in vitro and increased leukemogenic capacity in vivo. Although both G0 and S phase subpopulations were increased in LTHSCs with high MPL expression, LSC capacity was restricted to quiescent cells. Inhibition of MPL expression in CML LTHSCs reduced THPO-induced JAK/STAT signaling and leukemogenic potential. These same phenotypes were also present in LTHSCs from patients with CML, and patient LTHSCs with high MPL expression had reduced sensitivity to BCR-ABL tyrosine kinase inhibitor treatment but increased sensitivity to JAK inhibitors. Together, our studies identify MPL expression levels as a key determinant of heterogeneous leukemia-initiating capacity and drug sensitivity of CML LTHSCs and suggest that high MPL-expressing CML stem cells are potential targets for therapy. PMID- 26878177 TI - Obesity, PANDAS, Smoking, and Gun Violence. PMID- 26878176 TI - Production of high optical purity l-lactic acid from waste activated sludge by supplementing carbohydrate: effect of temperature and pretreatment time. AB - It has been widely accepted that the most environmentally beneficial way to treat waste activated sludge (WAS), the byproduct of municipal wastewater treatment plant, is to recover the valuable organic acid. However, the bio-conversion of lactic acid, one of the high added-value chemical, is seldom reported from WAS fermentation. In this paper, l-lactic acid was observed dominant in the WAS fermentation liquid with carbohydrate addition at ambient temperature. Furthermore, the effect of temperature on l-lactic acid and d-lactic acid production was fully discussed: two isomers were rapidly produced and consumed up in one day at mesophilic condition; and almost optically pure l-lactic acid was generated at thermophilic condition, yet time-consuming with yield of l-lactic acid enhancing by 52.9% compared to that at ambient temperature. The study mechanism showed that mesophilic condition was optimal for both production and consumption of l-lactic acid and d-lactic acid, while consumption of l-lactic acid and production of d-lactic acid were severely inhibited at thermophilic condition. Therefore, by maintaining thermophilic for 4 h in advance and subsequently fermenting mesophilic for 34 h, the concentration of l-lactic acid with optical activity of 98.3% was improved to 16.6 +/- 0.5 g COD/L at a high specific efficiency of 0.6097/d. PMID- 26878178 TI - A Nanny Versus Daycare: Is There a Right Choice? AB - As spring is on the horizon, my children begin to anticipate the end of the school year with thoughts of sleeping in, free days at the pool, and long evenings outside with friends. I, too, look forward to this time of the year, and a much needed hiatus from coaxing kids out of bed, making school lunches, and homework help in the evenings. However, I do not look forward to finding a new "kid sitter" for my preteens and teenager. Choice of childcare is perceived as perhaps one of the most stressful decisions parents must make for their children. Pediatic caregivers should discuss childcare as early as the prenatal visit and at all well visits thereafter. PMID- 26878175 TI - MLL-AF9- and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C. AB - Self-renewal is a hallmark of both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs); therefore, the identification of mechanisms that are required for LSC, but not HSC, function could provide therapeutic opportunities that are more effective and less toxic than current treatments. Here, we employed an in vivo shRNA screen and identified jumonji domain-containing protein JMJD1C as an important driver of MLL-AF9 leukemia. Using a conditional mouse model, we showed that loss of JMJD1C substantially decreased LSC frequency and caused differentiation of MLL-AF9- and homeobox A9-driven (HOXA9-driven) leukemias. We determined that JMJD1C directly interacts with HOXA9 and modulates a HOXA9 controlled gene-expression program. In contrast, loss of JMJD1C led to only minor defects in blood homeostasis and modest effects on HSC self-renewal. Together, these data establish JMJD1C as an important mediator of MLL-AF9- and HOXA9-driven LSC function that is largely dispensable for HSC function. PMID- 26878173 TI - Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. AB - BACKGROUND: Poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are rare and frequently lethal tumors that so far have not been subjected to comprehensive genetic characterization. METHODS: We performed next generation sequencing of 341 cancer genes from 117 patient-derived PDTCs and ATCs and analyzed the transcriptome of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTC). RESULTS: Compared to PDTCs, ATCs had a greater mutation burden, including a higher frequency of mutations in TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases. BRAF and RAS were the predominant drivers and dictated distinct tropism for nodal versus distant metastases in PDTC. RAS and BRAF sharply distinguished between PDTCs defined by the Turin (PDTC-Turin) versus MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, were markedly enriched in PDTCs and ATCs and had a striking pattern of co-occurrence with RAS mutations. While TERT promoter mutations were rare and subclonal in PTCs, they were clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) revealed a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs were BRAF-like irrespective of driver mutation. CONCLUSIONS: These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared with PDTC underscore their greater virulence and higher mortality. FUNDING: This work was supported in part by NIH grants CA50706, CA72597, P50-CA72012, P30-CA008748, and 5T32-CA160001; the Lefkovsky Family Foundation; the Society of Memorial Sloan Kettering; the Byrne fund; and Cycle for Survival. PMID- 26878179 TI - A 17-Year-Old Boy with Familial Adenomatous Polyposis and Unexpected Endoscopy Findings. PMID- 26878180 TI - An 8-Month-Old Infant with Persistent Stridor. PMID- 26878181 TI - Pediatric Gastroenterology. PMID- 26878182 TI - Clinical Review of Failure to Thrive in Pediatric Patients. AB - Failure to thrive (FTT) is a common problem that occurs when caloric intake is insufficient to maintain growth. For the majority of children it can be reversed with behavioral modifications and increased caloric provisions. In a minority of cases, FTT is the symptom of underlying organic disease. Routine evaluation with laboratory tests, imagining studies, and endoscopy results in an etiology of FTT in <1.4% of cases, and when investigations are positive the organic etiology is most often suspected based on history and/or physical examination. Therefore, these evaluations should be limited to those children with clear symptoms of organic disease and those who fail to grow with behavioral and nutritional interventions. PMID- 26878183 TI - Hereditary Pancreatitis. AB - A 13-year-old boy with a strong family history of hereditary pancreatitis was found to have a PRSS1 mutation after being tested at age 5 years during his first documented incident of pancreatitis. Since then, a multidisciplinary team has been treating him for the diagnosis of hereditary pancreatitis. His pain episodes increased in severity over the past several months such that the pain began to severely interfere with his daily life. After extensive discussion, a total pancreatectomy with auto islet cell transplant was performed. He is now pain free and does not require any insulin. This leads us to the questions of what is hereditary pancreatitis and how is it diagnosed? What are the management and follow-up strategies needed for these patients? This article addresses these questions and informs the reader about this diagnosis and the importance of having a high index of clinical suspicion. PMID- 26878184 TI - Nonalcoholic Fatty Liver Disease in Pediatrics. AB - A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease. PMID- 26878185 TI - Recurrent Pediatric Perianal Swelling. AB - Pediatric inflammatory bowel disease is a chronic gastrointestinal disease consisting of Crohn's disease (CD) and ulcerative colitis (UC). Both disease processes can share similar clinical symptoms including abdominal pain, diarrhea, hematochezia, and weight loss; CD can also be complicated by penetrating and fistulizing disease. Perianal skin tags, perianal abscesses, recto-cutaneous fistulae, and rectal stenosis are among the phenotypic characteristics of perianal CD. Current treatment strategies are focused on the surgical drainage of abscesses and the closure of fistulous tracts as well as controlling intestinal inflammation with the use of immunomodulators (6-mercaptopurine and methotrexate) and biologics (infliximab and adalimumab). Current guidelines by the American Gastroenterology Association and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend a combination of surgical intervention and medical management for the treatment of perianal CD. PMID- 26878186 TI - Eosinophilic Esophagitis: The "Not-So-Rare" Disease. AB - Eosinophilic esophagitis (EoE) is a relatively newly described disorder with increasing incidence. Patients with EoE may present at all ages from childhood through adulthood. Presenting symptoms may vary from feeding refusal, gagging, and/or vomiting in the younger population, dysphagia, chest pain, and abdominal pain in adolescents, as well as emergent food impactions. However, there are strict diagnostic criteria that must be met to make the diagnosis. Specifically, the diagnosis of EoE requires at least 15 eosinophils per high-powered field in the esophageal biopsies and symptoms of esophageal dysfunction after other causes, such as gastroesophageal reflux disease and proton pump inhibitor responsive esophageal eosinophilia, have been ruled out. Common treatments include diet modifications and/or topical corticosteroids. PMID- 26878187 TI - Charles Dickens and Barnaby Rudge: The First Description of Williams Syndrome? AB - Williams syndrome, a disorder caused by a genetic deletion and characterized by moderate intellectual disability with relatively strong language skills and a hypersocial personality, was first described in the medical literature in 1961. However, 120 years earlier, Charles Dickens wrote the novel Barnaby Rudge, which follows an "idiot" through London's Gordon Riots of 1780. We propose that Dickens based this character on a person he knew with Williams syndrome. Common features include an "elfin" face, decreased cognitive ability and dependence on a caretaker, strong language skills with emphatic and perseverative speech, anxiety, and an empathetic, overly trusting personality. In the novel, these traits lead the character Barnaby to be duped into actively participating in the riots, which nearly results in his hanging. This example of fiction providing a description of a disorder more detailed than that of medical journals more than a century later should encourage physicians to look to sources beyond traditional scientific articles for valuable clinical information. PMID- 26878188 TI - Interfacial properties of a carbyne-rich nanostructured carbon thin film in ionic liquid. AB - Nanostructured carbon sp(2) (ns-C) thin films with up to 30% of sp-coordinated atoms (carbynes) were produced in a high vacuum by the low kinetic energy deposition of carbon clusters produced in the gas phase and accelerated by a supersonic expansion. Immediately after deposition the ns-C films were immersed in situ in an ionic liquid electrolyte. The interfacial properties of ns-C films in the ionic liquid electrolyte were characterized by electrochemical impedance spectroscopy and cyclic voltammetry (CV). The so-prepared carbyne-rich electrodes showed superior electric double layer (EDL) capacitance and electric conductivity compared to ns-C electrodes containing only sp(2) carbon, showing the substantial influence of carbynes on the electrochemical properties of nanostructured carbon electrodes. PMID- 26878189 TI - Product Rearrangement from Altering a Single Residue in the Rice syn-Copalyl Diphosphate Synthase. AB - Through site-directed mutagenesis targeted at identification of the catalytic base in the rice (Oryza sativa) syn-copalyl diphosphate synthase OsCPS4, changes to a single residue (H501) were found to induce rearrangement rather than immediate deprotonation of the initially formed bicycle, leading to production of the novel compound syn-halimadienyl diphosphate. These mutational results are combined with quantum chemical calculations to provide insight into the underlying reaction mechanism. PMID- 26878190 TI - Variable laterality of corticospinal tract axons that regenerate after spinal cord injury as a result of PTEN deletion or knock-down. AB - Corticospinal tract (CST) axons from one hemisphere normally extend and terminate predominantly in the contralateral spinal cord. We previously showed that deleting the gene phosphatase and tensin homolog (PTEN) in the sensorimotor cortex enables CST axons to regenerate after spinal cord injury and that some regenerating axons extend along the "wrong" side. Here, we characterize the degree of specificity of regrowth in terms of laterality. PTEN was selectively deleted via cortical adeno-associated virus (AAV)-Cre injections in neonatal PTEN floxed mice. As adults, mice received dorsal hemisection injuries at T12 or complete crush injuries at T9. CST axons from one hemisphere were traced by unilateral biotinylated dextran amine (BDA) injections in PTEN-deleted mice with spinal cord injury and in noninjured PTEN-floxed mice that had not received AAV Cre. In noninjured mice, 97.9 +/- 0.7% of BDA-labeled axons in white matter and 88.5 +/- 1.0% of BDA-labeled axons in gray matter were contralateral to the cortex of origin. In contrast, laterality of CST axons that extended past a lesion due to PTEN deletion varied across animals. In some cases, regenerated axons extended predominantly on the ipsilateral side; in other cases, axons extended predominantly contralaterally, and in others, axons were similar in numbers on both sides. Similar results were seen in analyses of cases from previous studies using short hairpin (sh)RNA-mediated PTEN knock-down. These results indicate that CST axons that extend past a lesion due to PTEN deletion or knock-down do not maintain the contralateral rule of the noninjured CST, highlighting one aspect of how the resultant circuitry from regenerating axons may differ from that of the uninjured CST. J. Comp. Neurol. 524:2654-2676, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26878191 TI - Fibroblast growth factor (Fgf) 23 gene transcription depends on actin cytoskeleton reorganization. AB - FGF23 regulates renal phosphate and vitamin D metabolism. Loss of FGF23 results in massive calcification and rapid aging. FGF23 production is stimulated by 1,25(OH)2D3 and NFkappaB signaling. Here, we report that treatment of UMR106 osteoblast-like cells with 1,25(OH)2D3, inducing Fgf23 transcription, resulted in actin polymerization which was blocked by NFkappaB inhibitor wogonin. Interestingly, 1,25(OH)2D3-induced Fgf23 gene transcription was abolished by the actin microfilament-disrupting agent cytochalasin B, as well as by the inhibition of actin-regulating Rac1/PAK1 signaling. Our results provide strong evidence that actin redistribution regulated by the Rac1/PAK1 pathway participates in 1,25(OH)2D3-induced Fgf23 gene transcription. PMID- 26878193 TI - Pneumocystis pneumonia in non-HIV children: a 10-year retrospective study. AB - BACKGROUND: Pneumocytis pneumonia (PCP) is a life-threatening disease in non-HIV infected children. However, there have been few studies that have examined the clinical characteristics associated with PCP and outcomes for these pediatric patients. OBJECTIVES: A retrospective review was performed over a 10-year period to evaluate the clinical characteristics and outcome of non-HIV children diagnosed with PCP at Beijing Children's Hospital in China. RESULTS: A total of 60 non-HIV children diagnosed with PCP were included in the study. The overall mortality was 41.7% (25/60). Underlying diseases included connective tissue disease (n = 23; 38.3%), hematological disease (n = 14; 23.3%), nephrotic disease (n = 8; 13.3%) and immunodeficiency disease (n = 10; 16.7%). In all, 26/40 (65.0%) children developed PCP after receiving a follow-up large dose of glucocorticoid because of recurrent disease. Median time from beginning glucocorticoid medication to PCP diagnosis was 245.9 days (range: 14-2100 days). The area under the ROC curve of CD4/CD8 T cell levels for the diagnosis of PCP was 0.902 (95% confidence interval, 0.849-0.955). The analysis rendered an optimum cut-off value of 0.715 corresponding to 89.2% sensitivity and 80.4% specificity. Using a multivariate logistic regression model, three parameters were identified as significantly associated with mortality: LDH level, mechanical ventilation and co-infection. CONCLUSION: The outcome of PCP in non-HIV children remains poor. A critical stage for PCP development is administration of follow-up glucocorticoid without prophylaxis. CD4/CD8 ratio is a suitable biomarker for predicting PCP and diagnostic of PCP in non-HIV children. Poor prognostic factors include LDH level, need for mechanical ventilation and co-infection. PMID- 26878194 TI - Linker Modification Strategies To Control the Prostate-Specific Membrane Antigen (PSMA)-Targeting and Pharmacokinetic Properties of DOTA-Conjugated PSMA Inhibitors. AB - Since prostate-specific membrane antigen (PSMA) is up-regulated in nearly all stages of prostate cancer (PCa), PSMA can be considered as a viable diagnostic biomarker and treatment target in PCa. This project is focused on the development and evaluation of a series of compounds directed against PSMA. The modifications to the linker are designed to improve the binding potential and pharmacokinetics for theranostic application. In addition, the results help to further elucidate the structure-activity relationships (SAR) of the resulting PSMA inhibitors. Both in vitro and in vivo experiments of 18 synthesized PSMA inhibitor variants showed that systematic chemical modification of the linker has a significant impact on the tumor-targeting and pharmacokinetic properties. This approach can lead to an improved management of patients suffering from recurrent prostate cancer by the use of one radiolabeling precursor, which can be radiolabeled either with (68)Ga for diagnosis or with (177)Lu or (225)Ac for therapy. PMID- 26878192 TI - Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by In Situ Click Chemistry. AB - Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolide functionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a 16-component reaction (i.e., azide 2 and 15 alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the site-identification by ligand competitive saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogues with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1). PMID- 26878196 TI - Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean Older Adults With Mild Cognitive Impairment in Care Facilities. AB - PURPOSE: To examine effects of multivitamin supplements on cognitive function, serum homocysteine level, and depression of Korean older adults with mild cognitive impairment (MCI) in care facilities. DESIGN: A quasi-experimental pretest-posttest control group design was employed. METHODS: Forty-eight adults 65 years of age and older with MCI (experimental, n = 24; control, n = 24) who were living in care facilities in Gyeong-gi-do, Korea, were recruited. Multivitamin supplements as experimental treatment consisted of vitamin B6, B12, and folic acid. Multivitamin supplements were taken at a dosage of one pill every day for 12 weeks through the oral route. Measures were Mini Mental State Examination-Korean, serum homocysteine level, and Geriatric Depression Scale Short Form Korea Version. Collected data were analyzed using SPSS version 21.0 statistical software (SPSS Inc., Chicago, IL, USA). FINDINGS: There were significant effects of multivitamin supplements on cognitive function (F = 3.624, p = .021), serum homocysteine level (F = 6.974, p = .001), and depression (F = 10.849, p = .001). CONCLUSIONS: Multivitamin supplements increased cognitive function, and decreased serum homocysteine level and depression of Korean older adults with MCI in care facilities. CLINICAL RELEVANCE: Multivitamin supplements can be utilized for improving cognitive ability and for decreasing depression of Korean older adults with MCI in care facilities. PMID- 26878195 TI - Imprints of multiple glacial refugia in the Pyrenees revealed by phylogeography and palaeodistribution modelling of an endemic spider. AB - Mediterranean mountain ranges harbour highly endemic biota in islandlike habitats. Their topographic diversity offered the opportunity for mountain species to persist in refugial areas during episodes of major climatic change. We investigate the role of Quaternary climatic oscillations in shaping the demographic history and distribution ranges in the spider Harpactocrates ravastellus, endemic to the Pyrenees. Gene trees and multispecies coalescent analyses on mitochondrial and nuclear DNA sequences unveiled two distinct lineages with a hybrid zone around the northwestern area of the Catalan Pyrenees. The lineages were further supported by morphological differences. Climatic niche based species distribution models (SDMs) identified two lowland refugia at the western and eastern extremes of the mountain range, which would suggest secondary contact following postglacial expansion of populations from both refugia. Neutrality test and approximate Bayesian computation (ABC) analyses indicated that several local populations underwent severe bottlenecks followed by population expansions, which in combination with the deep population differentiation provided evidence for population survival during glacial periods in microrefugia across the mountain range, in addition to the main Atlantic and Mediterranean (western and eastern) refugia. This study sheds light on the complexities of Quaternary climatic oscillations in building up genetic diversity and local endemicity in the southern Europe mountain ranges. PMID- 26878197 TI - Do Solvated Electrons (e(aq)-) Reduce DNA Bases? A Gaussian 4 and Density Functional Theory-Molecular Dynamics Study. AB - The solvated electron (e(aq)-) is a primary intermediate after an ionization event that produces reductive DNA damage. Accurate standard redox potentials (E(o)) of nucleobases and of e(aq)- determine the extent of reaction of e(aq)- with nucleobases. In this work, E(o) values of e(aq)- and of nucleobases have been calculated employing the accurate ab initio Gaussian 4 theory including the polarizable continuum model (PCM). The Gaussian 4-calculated E(o) of e(aq)- ( 2.86 V) is in excellent agreement with the experimental one (-2.87 V). The Gaussian 4-calculated E(o) of nucleobases in dimethylformamide (DMF) lie in the range (-2.36 V to -2.86 V); they are in reasonable agreement with the experimental E(o) in DMF and have a mean unsigned error (MUE) = 0.22 V. However, inclusion of specific water molecules reduces this error significantly (MUE = 0.07). With the use of a model of e(aq)- nucleobase complex with six water molecules, the reaction of e(aq)- with the adjacent nucleobase is investigated using approximate ab initio molecular dynamics (MD) simulations including PCM. Our MD simulations show that e(aq)- transfers to uracil, thymine, cytosine, and adenine, within 10 to 120 fs and e(aq)- reacts with guanine only when a water molecule forms a hydrogen bond to O6 of guanine which stabilizes the anion radical. PMID- 26878200 TI - Computational design of donor-bridge-acceptor systems exhibiting pronounced quantum interference effects. AB - Quantum interference is a well-known phenomenon that dictates charge transport properties of single molecule junctions. However, reports on quantum interference in donor-bridge-acceptor molecules are scarce. This might be due to the difficulties in meeting the conditions for the presence of quantum interference in a donor-bridge-acceptor system. The electronic coupling between the donor, bridge, and acceptor moieties must be weak in order to ensure localised initial and final states for charge transfer. Yet, it must be strong enough to allow all bridge orbitals to mediate charge transfer. We present the computational route to the design of a donor-bridge-acceptor molecule that features the right balance between these contradicting requirements and exhibits pronounced interference effects. PMID- 26878198 TI - Using MD Simulations To Calculate How Solvents Modulate Solubility. AB - Here, our interest is in predicting solubility in general, and we focus particularly on predicting how the solubility of particular solutes is modulated by the solvent environment. Solubility in general is extremely important, both for theoretical reasons - it provides an important probe of the balance between solute-solute and solute-solvent interactions - and for more practical reasons, such as how to control the solubility of a given solute via modulation of its environment, as in process chemistry and separations. Here, we study how the change of solvent affects the solubility of a given compound. That is, we calculate relative solubilities. We use MD simulations to calculate relative solubility and compare our calculated values with experiment as well as with results from several other methods, SMD and UNIFAC, the latter of which is commonly used in chemical engineering design. We find that straightforward solubility calculations based on molecular simulations using a general small molecule force field outperform SMD and UNIFAC both in terms of accuracy and coverage of the relevant chemical space. PMID- 26878199 TI - 'To Measure is to Know.' Advancing the Use of Outcome Measures in the Physiotherapy Profession. PMID- 26878201 TI - Sc20C60: a volleyballene. AB - An exceptionally stable hollow cage containing 20 scandium atoms and 60 carbon atoms has been identified. This Sc20C60 molecular cluster has a Th point group symmetry and a volleyball-like shape that we refer to below as "Volleyballene". Electronic structure analysis shows that the formation of delocalized pi bonds between Sc atoms and the neighboring pentagonal rings made of carbon atoms is crucial for stabilizing the cage structure. A relatively large HOMO-LUMO gap (~1.4 eV) was found. The results of vibrational frequency analysis and molecular dynamics simulations both demonstrate that this Volleyballene molecule is exceptionally stable. PMID- 26878202 TI - High Thermal Stability of La2O3- and CeO2-Stabilized Tetragonal ZrO2. AB - Catalyst support materials of tetragonal ZrO2, stabilized by either La2O3 (La2O3 ZrO2) or CeO2 (CeO2-ZrO2), were synthesized under hydrothermal conditions at 200 degrees C with NH4OH or tetramethylammonium hydroxide as the mineralizer. From in situ synchrotron powder X-ray diffraction and small-angle X-ray scattering measurements, the calcined La2O3-ZrO2 and CeO2-ZrO2 supports were nonporous nanocrystallites that exhibited rectangular shapes with a thermal stability of up to 1000 degrees C in air. These supports had an average size of ~ 10 nm and a surface area of 59-97 m(2)/g. The catalysts Pt/La2O3-ZrO2 and Pt/CeO2-ZrO2 were prepared by using atomic layer deposition with varying Pt loadings from 6.3 to 12.4 wt %. Monodispersed Pt nanoparticles of ~ 3 nm were obtained for these catalysts. The incorporation of La2O3 and CeO2 into the t-ZrO2 structure did not affect the nature of the active sites for the Pt/ZrO2 catalysts for the water-gas shift reaction. PMID- 26878203 TI - Intracellular singlet oxygen photosensitizers: on the road to solving the problems of sensitizer degradation, bleaching and relocalization. AB - Selected singlet oxygen photosensitizers have been examined from the perspective of obtaining a molecule that is sufficiently stable under conditions currently employed to study singlet oxygen behavior in single mammalian cells. Reasonable predictions about intracellular sensitizer stability can be made based on solution phase experiments that approximate the intracellular environment (e.g., solutions containing proteins). Nevertheless, attempts to construct a stable sensitizer based solely on the expected reactivity of a given functional group with singlet oxygen are generally not sufficient for experiments in cells; it is difficult to construct a suitable chromophore that is impervious to all of the secondary and/or competing degradative processes that are present in the intracellular environment. On the other hand, prospects are reasonably positive when one considers the use of a sensitizer encapsulated in a specific protein; the local environment of the chromophore is controlled, degradation as a consequence of bimolecular reactions can be mitigated, and genetic engineering can be used to localize the encapsulated sensitizer in a given cellular domain. Also, the option of directly exciting oxygen in sensitizer-free experiments provides a useful complementary tool. These latter systems bode well with respect to obtaining more accurate control of the "dose" of singlet oxygen used to perturb a cell; a parameter that currently limits mechanistic studies of singlet oxygen-mediated cell signaling. PMID- 26878205 TI - Polarization effects on the interfacial conductivity in LaAlO3/SrTiO3 heterostructures: a first-principles study. AB - We studied the influence of uniaxial [100] strain (-1% to +1%) on the electron transport properties of a two-dimensional electron gas (2DEG) at the n-type interface of the LaAlO3/SrTiO3(LAO/STO) heterostructure (HS)-based slab system from the perspective of polarization effects via first-principles density functional theory calculations. We first analyzed the unstrained system, and found that the induced polarization toward the vacuum in the LAO film leads to a small charge carrier density on the order of 10(13) cm(-2) (less than the theoretical value of 3.3 * 10(14) cm(-2) from the superlattice-model-based polar catastrophe mechanism), which is in excellent agreement with the experimental values of oxygen-annealed LAO/STO HS samples. Upon applying [100] tensile strain on the STO substrate, we found a significant reduction of the induced polarization in the LAO film. This reduction weakens the driving force against charge transfer from LAO to STO, causing an increase in the interfacial charge carrier density. The uniaxial strain also leads to a decrease of the effective mass of interfacial mobile electrons, resulting in a higher electron mobility. These findings suggest that applying uniaxial [100] tensile strain on the STO substrate can significantly enhance the interfacial conductivity of the LAO/STO HS system, which gives a comprehensive explanation for experimental observations. In contrast, compressively strained LAO/STO systems show stronger LAO film polarization than the unstrained system, which reduces the interfacial charge carrier density and increases the electron effective mass, thus suppressing the interfacial conductivity. PMID- 26878206 TI - The interplay between cognitive risk and resilience factors in remitted depression: A network analysis. AB - BACKGROUND: Individuals in remission from depression are at increased risk for developing future depressive episodes. Several cognitive risk- and resilience factors have been suggested to account for this vulnerability. In the current study we explored how risk- and protective factors such as cognitive control, adaptive and maladaptive emotion regulation, residual symptomatology, and resilience relate to one another in a remitted depressed (RMD) sample. METHODS: We examined the relationships between these constructs in a cross-sectional dataset of 69 RMD patients using network analyses in order to obtain a comprehensive, data-driven view on the interplay between these constructs. We subsequently present an association network, a concentration network, and a relative importance network. RESULTS: In all three networks resilience formed the central hub, connecting perceived cognitive control (i.e., working memory complaints), emotion regulation, and residual symptomatology. The contribution of the behavioral measure for cognitive control in the network was negligible. Moreover, the directed relative importance network indicates bidirectional influences between these constructs, with all indicators of centrality suggesting a key role of resilience in remission from depression. LIMITATIONS: The presented findings are cross-sectional and networks are limited to a fixed set of key constructs in the literature pertaining cognitive vulnerability for depression. CONCLUSIONS: These findings indicate the importance of resilience to successfully cope with stressors following remission from depression. Further in-depth studies will be essential to identify the specific underlying resilience mechanisms that may be key to successful remission from depression. PMID- 26878207 TI - Synthesis of the rare disaccharide nigerose by structure-based design of a phosphorylase mutant with altered regioselectivity. AB - In the absence of the natural acceptor inorganic phosphate wild-type sucrose phosphorylase from Bifidobacterium adolescentis (BaSP) produces maltose (4-O alpha-d-glucopyranosyl-d-glucose) and kojibiose (2-O-alpha-d-glucopyranosyl-d glucose) as sole transfer products. A Q345F exchange switches the enzyme's regioselectivity from 2 to 3 exclusively, yielding the rare sugar nigerose (3-O alpha-d-glucopyranosyl-d-glucose, sakebiose). PMID- 26878208 TI - Plasmalemma Vesicle-Associated Protein Has a Key Role in Blood-Retinal Barrier Loss. AB - Loss of blood-retinal barrier (BRB) properties induced by vascular endothelial growth factor (VEGF) and other factors is an important cause of diabetic macular edema. Previously, we found that the presence of plasmalemma vesicle-associated protein (PLVAP) in retinal capillaries associates with loss of BRB properties and correlates with increased vascular permeability in diabetic macular edema. In this study, we investigated whether absence of PLVAP protects the BRB from VEGF induced permeability. We used lentiviral-delivered shRNA or siRNA to inhibit PLVAP expression. The barrier properties of in vitro BRB models were assessed by measuring transendothelial electrical resistance, permeability of differently sized tracers, and the presence of endothelial junction complexes. The effect of VEGF on caveolae formation was studied in human retinal explants. BRB loss in vivo was studied in the mouse oxygen-induced retinopathy model. The inhibition of PLVAP expression resulted in decreased VEGF-induced BRB permeability of fluorescent tracers, both in vivo and in vitro. PLVAP inhibition attenuated transendothelial electrical resistance reduction induced by VEGF in BRB models in vitro and significantly increased transendothelial electrical resistance of the nonbarrier human umbilical vein endothelial cells. Furthermore, PLVAP knockdown prevented VEGF-induced caveolae formation in retinal explants but did not rescue VEGF-induced alterations in endothelial junction complexes. In conclusion, PLVAP is an essential cofactor in VEGF-induced BRB permeability and may become an interesting novel target for diabetic macular edema therapy. PMID- 26878209 TI - The Protectin PCTR1 Is Produced by Human M2 Macrophages and Enhances Resolution of Infectious Inflammation. AB - Inflammation and its natural resolution are host-protective responses triggered by infection or injury. The resolution phase of inflammation is regulated by enzymatically produced specialized pro-resolving mediators. We recently identified a new class of peptide-conjugated specialized pro-resolving mediators that carry potent tissue regenerative actions that belong to the protectin family and are coined protectin conjugates in tissue regeneration (PCTR). Herein, with the use of microbial-induced peritonitis in mice and liquid chromatography-tandem mass spectrometry-based lipid mediator metabololipidomics, we found that PCTR1 is temporally regulated during self-resolving infection. When administered at peak of inflammation, PCTR1 enhanced macrophage recruitment and phagocytosis of Escherichia coli, decreased polymorphonuclear leukocyte infiltration, and counter regulated inflammation-initiating lipid mediators, including prostaglandins. In addition, biologically produced PCTR1 promoted human monocyte and macrophage migration in a dose-dependent manner (0.001 to 10.0 nmol/L). We prepared PCTR1 via organic synthesis and confirmed that synthetic PCTR1 increased macrophage and monocyte migration, enhanced macrophage efferocytosis, and accelerated tissue regeneration in planaria. With human macrophage subsets, PCTR1 levels were significantly higher in M2 macrophages than in M1 phenotype, along with members of the resolvin conjugates in tissue regeneration and maresin conjugate families. In contrast, M1 macrophages gave higher levels of cysteinyl leukotrienes. Together, these results demonstrate that PCTR1 is a potent monocyte/macrophage agonist, regulating key anti-inflammatory and pro-resolving processes during bacterial infection. PMID- 26878210 TI - alphaB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial Mesenchymal Transition. AB - Subretinal fibrosis is an end stage of neovascular age-related macular degeneration, characterized by fibrous membrane formation after choroidal neovascularization. An initial step of the pathogenesis is an epithelial mesenchymal transition (EMT) of retinal pigment epithelium cells. alphaB crystallin plays multiple roles in age-related macular degeneration, including cytoprotection and angiogenesis. However, the role of alphaB-crystallin in subretinal EMT and fibrosis is unknown. Herein, we showed attenuation of subretinal fibrosis after regression of laser-induced choroidal neovascularization and a decrease in mesenchymal retinal pigment epithelium cells in alphaB-crystallin knockout mice compared with wild-type mice. alphaB crystallin was prominently expressed in subretinal fibrotic lesions in mice. In vitro, overexpression of alphaB-crystallin induced EMT, whereas suppression of alphaB-crystallin induced a mesenchymal-epithelial transition. Transforming growth factor-beta2-induced EMT was further enhanced by overexpression of alphaB crystallin but was inhibited by suppression of alphaB-crystallin. Silencing of alphaB-crystallin inhibited multiple fibrotic processes, including cell proliferation, migration, and fibronectin production. Bone morphogenetic protein 4 up-regulated alphaB-crystallin, and its EMT induction was inhibited by knockdown of alphaB-crystallin. Furthermore, inhibition of alphaB-crystallin enhanced monotetraubiquitination of SMAD4, which can impair its nuclear localization. Overexpression of alphaB-crystallin enhanced nuclear translocation and accumulation of SMAD4 and SMAD5. Thus, alphaB-crystallin is an important regulator of EMT, acting as a molecular chaperone for SMAD4 and as its potential therapeutic target for preventing subretinal fibrosis development in neovascular age-related macular degeneration. PMID- 26878212 TI - Circulating Extracellular Histones Are Clinically Relevant Mediators of Multiple Organ Injury. AB - Extracellular histones are a damage-associated molecular pattern (DAMP) involved in the pathogenesis of various diseases. The mechanisms of histone-mediated injury in certain organs have been extensively studied, but an understanding of the pathophysiological role of histone-mediated injury in multiple organ injury remains elusive. To elucidate this role, we systemically subjected C57BL/6 mice to various doses of histones and performed a chronological evaluation of the morphological and functional changes in the lungs, liver, and kidneys. Notably, histone administration ultimately led to death after a dose-dependent aggravation of multiple organ injury. In chronological studies, pulmonary and hepatic injuries occurred within 15 minutes, whereas renal injuries presented at a later phase, suggesting that susceptibility to extracellular histones varies among organs. Histones bound to pulmonary and hepatic endothelial cells immediately after administration, leading to endothelial damage, which could be ameliorated by pretreatment with heparin. Furthermore, release of another DAMP, high-mobility group protein box 1, followed the histone-induced tissue damage, and an antibody against the molecule ameliorated hepatic and renal failure in a late phase. These findings indicate that extracellular histones induce multiple organ injury in two progressive stages-direct injury to endothelial cells and the subsequent release of other DAMPs-and that combination therapies against extracellular histones and high-mobility group protein box 1 may be a promising strategy for treating multiple organ injury. PMID- 26878211 TI - Dynamic Change of Polarity in Primary Cultured Spheroids of Human Colorectal Adenocarcinoma and Its Role in Metastasis. AB - Intestinal epithelial cells possess apical-basal polarity, which governs the exchange of nutrients and waste. Perturbation of cell polarity appears to be a general feature of cancers, although most colorectal cancers are differentiated adenocarcinomas, in which polarity is maintained to some extent. Little is known about the role of dysregulated polarity in cancer. The cancer tissue-originated spheroid method was applied to the preparation and culture of spheroids. Spheroids were cultured in suspension or in type I collagen gel. Polarity was assessed by IHC of apical markers and electron microscopy. Two types of polarity status in spheroids were observed: apical-in, with apical membrane located at cavities inside the spheroids in type I collagen gel; and apical-out, with apical membrane located at the outermost layer of spheroids in suspension. These polarities were highly interchangeable. Inhibitors of Src and dynamin attenuated the polarity switch. In patients, clusters of cancer cells that invaded vessels had both apical-in and apical-out morphologic features, whereas primary and metastatic tumors had apical-in features. In a mouse liver metastasis model, apical-out spheroids injected into the portal vein became apical-in spheroids in the liver within a few days. Inhibitors of Src and dynamin significantly decreased liver metastasis. Polarity switching was observed in spheroids and human cancer. The polarity switch was critical in an experimental liver metastasis model. PMID- 26878213 TI - Actin-Depolymerizing Factor and Cofilin-1 Have Unique and Overlapping Functions in Regulating Intestinal Epithelial Junctions and Mucosal Inflammation. AB - The actin cytoskeleton is a crucial regulator of the intestinal mucosal barrier, controlling the assembly and function of epithelial adherens and tight junctions (AJs and TJs). Junction-associated actin filaments are dynamic structures that undergo constant turnover. Members of the actin-depolymerizing factor (ADF) and cofilin protein family play key roles in actin dynamics by mediating filament severing and polymerization. We examined the roles of ADF and cofilin-1 in regulating the structure and functions of AJs and TJs in the intestinal epithelium. Knockdown of either ADF or cofilin-1 by RNA interference increased the paracellular permeability of human colonic epithelial cell monolayers to small ions. Additionally, cofilin-1, but not ADF, depletion increased epithelial permeability to large molecules. Loss of either ADF or cofilin-1 did not affect the steady-state morphology of AJs and TJs but attenuated de novo junctional assembly. The observed defects in AJ and TJ formation were accompanied by delayed assembly of the perijunctional filamentous actin belt. A total loss of ADF expression in mice did not result in a defective mucosal barrier or in spontaneous gut inflammation. However, ADF-null mice demonstrated increased intestinal permeability and exaggerated inflammation during dextran sodium sulfate-induced colitis. Our findings demonstrate novel roles for ADF and cofilin 1 in regulating the remodeling and permeability of epithelial junctions, as well as the role of ADF in limiting the severity of intestinal inflammation. PMID- 26878216 TI - Near-infrared-spectroscopic study on processing of sounds in the brain; a comparison between native and non-native speakers of Japanese. AB - Conclusions The result suggested that mother tongue Japanese and non- mother tongue Japanese differ in their pattern of brain dominance when listening to sounds from the natural world-in particular, insect sounds. These results reveal significant support for previous findings from Tsunoda (in 1970). Objectives This study concentrates on listeners who show clear evidence of a 'speech' brain vs a 'music' brain and determines which side is most active in the processing of insect sounds, using with near-infrared spectroscopy. Methods The present study uses 2-channel Near Infrared Spectroscopy (NIRS) to provide a more direct measure of left- and right-brain activity while participants listen to each of three types of sounds: Japanese speech, Western violin music, or insect sounds. Data were obtained from 33 participants who showed laterality on opposite sides for Japanese speech and Western music. Results Results showed that a majority (80%) of the MJ participants exhibited dominance for insect sounds on the side that was dominant for language, while a majority (62%) of the non-MJ participants exhibited dominance for insect sounds on the side that was dominant for music. PMID- 26878214 TI - Fatty Acid Ethyl Esters Are Less Toxic Than Their Parent Fatty Acids Generated during Acute Pancreatitis. AB - Although ethanol causes acute pancreatitis (AP) and lipolytic fatty acid (FA) generation worsens AP, the contribution of ethanol metabolites of FAs, ie, FA ethyl esters (FAEEs), to AP outcomes is unclear. Previously, pancreata of dying alcoholics and pancreatic necrosis in severe AP, respectively, showed high FAEEs and FAs, with oleic acid (OA) and its ethyl esters being the most abundant. We thus compared the toxicities of FAEEs and their parent FAs in severe AP. Pancreatic acini and peripheral blood mononuclear cells were exposed to FAs or FAEEs in vitro. The triglyceride of OA (i.e., glyceryl tri-oleate) or OAEE was injected into the pancreatic ducts of rats, and local and systemic severities were studied. Unsaturated FAs at equimolar concentrations to FAEEs induced a larger increase in cytosolic calcium, mitochondrial depolarization, and necro apoptotic cell death. Glyceryl tri-oleate but not OAEE resulted in 70% mortality with increased serum OA, a severe inflammatory response, worse pancreatic necrosis, and multisystem organ failure. Our data show that FAs are more likely to worsen AP than FAEEs. Our observations correlate well with the high pancreatic FAEE concentrations in alcoholics without pancreatitis and high FA concentrations in pancreatic necrosis. Thus, conversion of FAs to FAEE may ameliorate AP in alcoholics. PMID- 26878217 TI - Carbon quantum dots directly generated from electrochemical oxidation of graphite electrodes in alkaline alcohols and the applications for specific ferric ion detection and cell imaging. AB - Carbon quantum dots (CQDs) are attracting tremendous interest owing to their low toxicity, water dispersibility, biocompatibility, optical properties and wide applicability. Herein, CQDs with an average diameter of (4.0 +/- 0.2) nm and high crystallinity were produced simply from the electrochemical oxidation of a graphite electrode in alkaline alcohols. The as-formed CQDs dispersion was colourless but the dispersion gradually changed to bright yellow when stored in ambient conditions. Based on UV-Vis absorption, fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR) and high-resolution transmission electron microscopy (HRTEM), this colour change appeared to be due to oxygenation of surface species over time. Furthermore, the CQDs were used in specific and sensitive detection of ferric ion (Fe(3+)) with broad linear ranges of 10-200 MUM with a low limit of detection of 1.8 MUM (S/N = 3). The application of the CQDs for Fe(3+) detection in tap water was demonstrated and the possible mechanism was also discussed. Finally, based on their good characteristics of low cytotoxicity and excellent biocompatibility, the CQDs were successfully applied to cell imaging. PMID- 26878215 TI - Initial Suppression of Transforming Growth Factor-beta Signaling and Loss of TGFBI Causes Early Alveolar Structural Defects Resulting in Bronchopulmonary Dysplasia. AB - Septation of the gas-exchange saccules of the morphologically immature mouse lung requires regulated timing, spatial direction, and dosage of transforming growth factor (TGF)-beta signaling. We found that neonatal hyperoxia acutely initially diminished saccular TGF-beta signaling coincident with alveolar simplification. However, sustained hyperoxia resulted in a biphasic response and subsequent up regulation of TGF-beta signaling, ultimately resulting in bronchopulmonary dysplasia. Significantly, we found that the TGF-beta-induced matricellular protein (TGFBI) was similarly biphasically altered in response to hyperoxia. Moreover, genetic ablation revealed that TGFBI was required for normal alveolar structure and function. Although the phenotype was not neonatal lethal, Tgfbi deficient lungs were morphologically abnormal. Mutant septal tips were stunted, lacked elastin-positive tips, exhibited reduced proliferation, and contained abnormally persistent alveolar alpha-smooth muscle actin myofibroblasts. In addition, Tgfbi-deficient lungs misexpressed TGF-beta-responsive follistatin and serpine 1, and transiently suppressed myofibroblast platelet-derived growth factor alpha differentiation marker. Finally, despite normal lung volume, Tgfbi null lungs displayed diminished elastic recoil and gas exchange efficiency. Combined, these data demonstrate that initial suppression of the TGF-beta signaling apparatus, as well as loss of key TGF-beta effectors (like TGFBI), underlies early alveolar structural defects, as well as long-lasting functional deficits routinely observed in chronic lung disease of infancy patients. These studies underline the complex (and often contradictory) role of TGF-beta and indicate a need to design studies to associate alterations with initial appearance of phenotypical changes suggestive of bronchopulmonary dysplasia. PMID- 26878219 TI - Prompt chlorophyll a fluorescence as a rapid tool for diagnostic changes in PSII structure inhibited by salt stress in Perennial ryegrass. AB - Perennial ryegrass (Lolium perenne L.) is one of the most popular grass species in Europe. It is commonly used for establishing the lawns in urban areas, where the salt stress is one of the major environmental conditions limiting its growth. The basic aim of this study was the detailed in vivo analysis of the changes in photosynthetic efficiency, induced by salt stress, of two lawn varieties of Perennial ryegrass and to find out the variety of better properties to create lawn on the soils contaminated with salt. Two lawn varieties of L. perenne L. were used: Nira and Roadrunner. The salinization was applied 8 weeks after sowing by adding NaCl in water solution (0, 0.15, and 0.30 M). The measurements were carried out 8 times: 0, 24, 48, 96, 144, 192, 240 and 288 h after salinization. Our results revealed that the disturbance of PSII function could easily be estimated by measuring chlorophyll a fluorescence and analyzing that signal by JIP-test. Our work allowed to identify various limiting parameters of photosynthetic efficiency of perennial ryegrass lawn varieties grown under salt stress conditions. This knowledge can allow for selection of plants with a higher potential photosynthetic efficiency (vitality) during salt stress conditions, that can be used successfully neighboring roads, where salt is applied. PMID- 26878218 TI - Dual calibrated dosimeter for simultaneous measurements of erythemal and vitamin D effective solar ultraviolet radiation. AB - A miniaturized ultraviolet radiation (UV) dosimeter based on polyphenylene oxide (PPO) has been dual calibrated for both erythemal and vitamin D effective exposures (UVB 280 - 320 nm) over extended periods up to five days. Optimal human health requires a balanced amount of UVB exposure as both too much and too little have different but serious potential health consequences. Dosimetry is an established method of measuring specific UV exposures to an object or subject. PPO dosimeters have previously been used to measure the erythemally effective UV exposure. An extension of this use is to dual calibrate the miniaturized dosimeter which will also enable measurement of vitamin D effective exposures. By calibration to the erythemal and vitamin D effective action spectra, PPO dosimeters were able to record both types of biologically effective exposure as both are active within the UVB waveband. Dose response tests were conducted in each season by exposure to solar UV with the corresponding dual calibrations made for each season. The calibration provided an R(2) of 0.95-0.99 for erythemal UV and an R(2) of 0.99 for vitamin D effective UV. The successful outcome of this testing has established that PPO is suitable for use as a long term, dual calibrated dosimeter provided the film is seasonally calibrated. This enables one dosimeter to provide two sets of exposure results. The combination of dual calibration and the long term exposure potential of PPO makes the PPO dosimeter more versatile and increases the scope of UV field research on erythemal UV and vitamin D effective UV in the future. PMID- 26878220 TI - A pilot study investigating whether focusing on body functionality can protect women from the potential negative effects of viewing thin-ideal media images. AB - This pilot study explored whether focusing on body functionality (i.e., everything the body can do) can protect women from potential harmful effects of exposure to thin-ideal images. Seventy women (Mage=20.61) completed an assignment wherein they either described the functionality of their body or the routes that they often travel (control). Afterward, participants were exposed to a series of thin-ideal images. Appearance and functionality satisfaction were measured before the assignment; appearance and functionality satisfaction, self-objectification, and body appreciation were measured after exposure. Results showed that participants who focused on body functionality experienced greater functionality satisfaction and body appreciation compared to control participants. Therefore, focusing on body functionality could be a beneficial individual-level technique that women can use to protect and promote a positive body image in the face of thin-ideal images. Research including a condition wherein participants are exposed to (product-only) control images is necessary to draw firmer conclusions. PMID- 26878221 TI - Modeling flood reduction effects of low impact development at a watershed scale. AB - Low impact development (LID) is a land development approach that seeks to mimic a site's pre-development hydrology. This study is a case study that assessed flood reduction capabilities of large-scale adoption of LID practices in an urban watershed in central Illinois using the Personal Computer Storm Water Management Model (PCSWMM). Two flood metrics based on runoff discharge were developed to determine action flood (43 m(3)/s) and major flood (95 m(3)/s). Four land use scenarios for urban growth were evaluated to determine the impacts of urbanization on runoff and flooding. Flood attenuation effects of porous pavement, rain barrel, and rain garden at various application levels were also evaluated as retrofitting technologies in the study watershed over a period of 30 years. Simulation results indicated that increase in urban land use from 50 to 94% between 1992 and 2030 increased average annual runoff and flood events by more than 30%, suggesting that urbanization without sound management would increase flood risks. The various implementation levels of the three LID practices resulted in 3-47% runoff reduction in the study watershed. Flood flow events that include action floods and major floods were also reduced by 0-40%, indicating that LID practices can be used to mitigate flood risk in urban watersheds. The study provides an insight into flood management with LID practices in existing urban areas. PMID- 26878222 TI - Polygenic phenotypic plasticity moderates the effects of severe childhood abuse on depressive symptom severity in adulthood: A 5-year prospective cohort study. AB - Objective To test the phenotypic plasticity framework using a polygenic approach in a prospective depression cohort of primary care attendees with and without histories of severe childhood abuse. Methods Depressive symptoms were assessed at baseline and annually for 5 years post-baseline using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9) among 288 adult primary care attendees. Twelve polymorphisms in nine genes were genotyped and polygenic phenotypic plasticity allelic load (PAL) calculated. Linear mixed models assessed differences in depressive symptom severity over the 5-year follow up period by PAL and history of severe childhood abuse. Results A higher PAL conferred greater depressive symptom severity among those with a history of severe childhood abuse but conferred significantly lower symptom severity among those without this history. Importantly, this interaction withstood adjustments for important covariates (e.g., antidepressant use, comorbid anxiety) and was stable over the 5 years of observation. Conclusions Aligned with the phenotypic plasticity framework, depressive symptom severity was dependent on the interaction between PAL and history of severe childhood abuse in a "for better and for worse" manner. Measures of polygenic phenotypic plasticity, such as ours, may serve as a trait marker of sensitivity to negative and potentially positive environmental influences. PMID- 26878223 TI - The aetiology of post-traumatic stress following childbirth: a meta-analysis and theoretical framework. AB - There is evidence that 3.17% of women report post-traumatic stress disorder (PTSD) after childbirth. This meta-analysis synthesizes research on vulnerability and risk factors for birth-related PTSD and refines a diathesis-stress model of its aetiology. Systematic searches were carried out on PsycINFO, PubMed, Scopus and Web of Science using PTSD terms crossed with childbirth terms. Studies were included if they reported primary research that examined factors associated with birth-related PTSD measured at least 1 month after birth. In all, 50 studies (n = 21 429) from 15 countries fulfilled inclusion criteria. Pre-birth vulnerability factors most strongly associated with PTSD were depression in pregnancy (r = 0.51), fear of childbirth (r = 0.41), poor health or complications in pregnancy (r = 0.38), and a history of PTSD (r = 0.39) and counselling for pregnancy or birth (r = 0.32). Risk factors in birth most strongly associated with PTSD were negative subjective birth experiences (r = 0.59), having an operative birth (assisted vaginal or caesarean, r = 0.48), lack of support (r = -0.38) and dissociation (r = 0.32). After birth, PTSD was associated with poor coping and stress (r = 0.30), and was highly co-morbid with depression (r = 0.60). Moderator analyses showed that the effect of poor health or complications in pregnancy was more apparent in high-risk samples. The results of this meta-analysis are used to update a diathesis-stress model of the aetiology of postpartum PTSD and can be used to inform screening, prevention and intervention in maternity care. PMID- 26878224 TI - Advances in Antiviral Therapies Targeting Toll-like Receptors. AB - INTRODUCTION: Organisms have evolved a rapid and non-specific way to defend themselves via Toll-like receptors (TLRs), which recognize specific signatures present on invading microbes and viruses. Once detected, these receptors flood the cell with cytokines and IFNs that not only help to eradicate the invading viruses but also activate the adaptive immune response. Owing to difficulties in viral detection, a whole class of TLRs is dedicated to sensing viral nucleic acids, while other TLRs detect viral coat proteins and aid in establishing antiviral immunity. To protect humans better, TLRs and their downstream mediators can be used as potential drug targets, which can be either activated or inhibited, to counter viral infections. AREAS COVERED: The current review focuses on TLR-targeting investigational drugs developed to treat viral diseases and virus-induced complications. EXPERT OPINION: TLRs are a good choice for eradicating viral infections because they can fine-tune the immune response. However, TLRs should be exploited carefully, as there have been instances where their activation has led to unwanted responses in terms of both immune and viral activation. Therefore, more focus should be placed on novel drugs that can induce significant and long-term immunity, while concomitantly alleviating side effects. PMID- 26878225 TI - Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features. AB - Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26878226 TI - Use of Clinical Data to Predict Appendicitis in Patients with Equivocal US Findings. AB - Purpose To determine the incremental value of clinical data in patients with ultrasonographic (US) examinations that were interpreted as being equivocal for acute appendicitis. Materials and Methods Institutional review board approval, with a waiver of informed consent, was obtained for this analysis of clinical and imaging data in patients younger than 18 years old who were evaluated for acute appendicitis. Findings from US examinations were reported in a structured fashion, including two possible equivocal impressions. Clinical data were captured as Pediatric Appendicitis (PAS) or Alvarado scores and considered as categoric (high, intermediate, or low likelihood) and continuous variables to simulate stratification of equivocal US examinations to predict appendicitis. Receiver operating characteristic curves were used to define score cutoffs, and logistic regression was used to assess individual clinical variables as predictors of appendicitis. Results The study population was made up of 776 patients (mean age, 11.7 years +/- 3.7), with 429 (55.2%) girls. A total of 203 (26%) patients had appendicitis. US had a negative predictive value of 96.2% and a positive predictive value of 93.3% for depicting appendicitis, with 89 of 782 (11.4%) equivocal examinations. Categoric PAS and Alvarado scores were equivocal for 59.5% (53 of 89) and 50.6% (45 of 89) of equivocal US examinations, respectively. Categoric low- and high-likelihood PAS and Alvarado scores correctly predicted the presence of appendicitis in 61.1% (22 of 36) and 77.3% (34 of 44) of equivocal US examinations, respectively. As continuous variables, a PAS or Alvarado score of 5 or lower could be used to exclude appendicitis, with a 80.8% (21 of 26) and 90% (18 of 20) negative predictive value, respectively. Conclusion The study confirms the excellent performance of US for depicting pediatric appendicitis. In the subset of equivocal US examinations, a low clinical score (<=5) may be used to identify patients with a low likelihood of having appendicitis. ((c)) RSNA, 2016. PMID- 26878227 TI - Serrated Polyps at CT Colonography: Prevalence and Characteristics of the Serrated Polyp Spectrum. AB - Purpose To report the prevalence and characteristics of serrated polyps identified in a large, average-risk population undergoing screening computed tomographic (CT) colonography. Materials and Methods This HIPAA-compliant retrospective study was approved by the institutional review board of the University of Wisconsin School of Medicine and Public Health. The need for informed consent was waived. Nine thousand six hundred examinations from 8289 patients were enrolled in a single-institution CT colonography-based screening program (from 2004 to 2011) and were evaluated for the presence of nondiminutive serrated lesions and advanced adenomas. The prevalence and characteristics of these lesions were tabulated. Generalized estimating equation regressions of polyp characteristics that may contribute to visualization of serrated lesions were investigated, including polyp size, location, and morphologic appearance; histologic findings; and presence or absence of contrast material tagging. Results Nondiminutive serrated lesions (>=6 mm) were seen at CT colonography based screening with a prevalence of 3.1% (254 of 8289 patients). Sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) constituted 36.8% (137 of 372) and 4.3% (16 of 372) of serrated lesions, respectively; hyperplastic polyps (HPs) accounted for 58.9% (219 of 372 lesions). SSA and TSA tended to be large (mean size, 10.6 mm and 14.1 mm, respectively), with size categories and polyp subgroups significantly associated (P < .0001). SSA tended to be proximal in location (91.2%, 125 of 137 lesions) and flat in morphologic appearance (39.4%, 54 of 137 lesions) compared with TSA and HP. The presence of high-grade dysplasia in serrated lesions was uncommon when compared with advanced adenomas (one of 372 lesions vs 22 of 395 lesions, respectively; P < .0001). Multivariate analysis showed that contrast material tagging markedly improved serrated polyp detection with an odds ratio of 40.4 (95% confidence interval: 10.1, 161.4). Conclusion Serrated lesions are seen at CT colonography-based screening with a nondiminutive prevalence of 3.1%. These lesions tend to be large, flat, and proximal in location. Adherent contrast material coating on these polyps aids in their detection, despite an often flat morphologic appearance. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26878228 TI - A review of the ligands and related targeting strategies for active targeting of paclitaxel to tumours. AB - It has been 30 years since the discovery of the anti-tumour property of paclitaxel (PTX), which has been successfully applied in clinic for the treatment of carcinomas of the lungs, breast and ovarian. However, PTX is poorly soluble in water and has no targeting and selectivity to tumour tissue. Recent advances in active tumour targeting of PTX delivery vehicles have addressed some of the issues related to lack of solubility in water and non-specific toxicities associated with PTX. These PTX delivery vehicles are designed for active targeting to specific cancer cells by the addition of ligands for recognition by specific receptors/antigens on cancer cells. This article will focus on various ligands and related targeting strategies serving as potential tools for active targeting of PTX to tumour tissues, illustrating their use in different tumour models. This review also highlights the need of further studies on the discovery of receptors in different cells of specific organ and ligands with binding efficiency to these specific receptors. PMID- 26878229 TI - The American Academy of Clinical Neuropsychology, National Academy of Neuropsychology, and Society for Clinical Neuropsychology (APA Division 40) 2015 TCN Professional Practice and 'Salary Survey': Professional Practices, Beliefs, and Incomes of U.S. Neuropsychologists. AB - OBJECTIVE: The current survey updated professional practice and income information pertaining to clinical neuropsychology. METHODS: Doctoral-level members of the American Academy of Clinical Neuropsychology, Division 40 (Clinical Neuropsychology) of the American Psychological Association, and the National Academy of Neuropsychology and other neuropsychologists, as well as postdoctoral trainees in the Association of Postdoctoral Programs in Clinical Neuropsychology and at other training sites were invited to participate in a web based survey in early 2015. The sample of 1777 respondents, of whom 1579 were doctoral-level practitioners and 198 were postdoctoral trainees, was larger than the prior 2010 income and practice survey. RESULTS: The substantial proportional change in gender has continued, with women now a clear majority in the postdoctoral trainee sample as well as in the practitioner sample. Dissimilar from the median age trajectory of American Psychological Association members, the median age of clinical neuropsychologists remains essentially unchanged since 1989, indicating a substantial annual influx of young neuropsychologists. The question of whether the Houston Conference training model has become an important influence in the specialty can now be considered settled in the affirmative among postdoctoral trainees and practitioners. Testing assistant usage remains commonplace, and continues to be more common in institutions. The vast majority of clinical neuropsychologists work full-time and very few are unemployed and seeking employment. The numbers of neuropsychologists planning to retire in the coming 5-10 years do not suggest a "baby boomer" effect or an unexpected bolus of planned retirements in the next 10 years that would be large enough to be worrisome. Average length of time reported for evaluations appears to be increasing across time. The most common factors affecting evaluation length were identified, with the top three being: (1) goal of evaluation, (2) stamina/health of examinee, and (3) age of examinee. Pediatric specialists remain more likely than others to work part-time, more likely to work in institutions, report lower incomes than respondents with a lifespan professional identity, and are far more likely to be women. Incomes continue to vary considerably by years of clinical practice, work setting, amount of forensic practice, state, and region of country. Neurologists are the number one referral source in institutions and in private practice, as well as for pediatric, adult, and lifespan practitioners. Learning disability is no longer among the top five conditions seen by pediatric neuropsychologists; traumatic brain injury and seizure disorder are common reasons for clinical evaluations at all age ranges. There is a continued increase in forensic practice and a clear consensus on the use of validity testing. There is a substantial interest in subspecialization board certification, with the greatest interest evident among postdoctoral trainees. Income satisfaction, job satisfaction, and work-life balance satisfaction are higher for men. Job satisfaction varies across general work setting and across age range of practice. Work-life balance satisfaction is moderately correlated with income satisfaction and job satisfaction. Again in this five-year interval survey, a substantial majority of respondents reported increased incomes, despite experiencing substantial negative practice effects related to changes in the US health care system. Numerous breakdowns related to income and professional activities are provided. CONCLUSIONS: Professional practice survey information continues to provide valuable perspectives regarding consistency and change in the activities, beliefs, and incomes of US clinical neuropsychologists. PMID- 26878234 TI - Evaluating the evidence for and against the use of IOLs in infants and young children. AB - Congenital cataracts account for 5-20% of childhood blindness worldwide. In the US, the prevalence of visually significant infantile cataracts is anywhere from 3 4 per 10,000 live births. Infantile cataracts need to be removed early in life in order to prevent the onset of deprivation amblyopia. As a result, cataract surgery is usually performed between age 4-8 weeks depending on the laterality and severity of the cataract. Given advances in the field, pediatric cataract surgery is now a safe and effective intervention for infants, but good visual outcomes require occlusion therapy and optical correction. This review will address current perspectives on the use of intraocular lenses to optically correct infants and young children after cataract surgery, as well as novel designs for intraocular lenses and directions for future research. PMID- 26878235 TI - Controlling spin relaxation with a cavity. AB - Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the rate of spontaneous emission can be greatly enhanced by placing the quantum system in a resonant cavity. This effect has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, and is essential for the realization of high-efficiency single-photon sources. Here we report the application of this idea to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity with a high quality factor and a small mode volume, we reach the regime in which spontaneous emission constitutes the dominant mechanism of spin relaxation. The relaxation rate is increased by three orders of magnitude as the spins are tuned to the cavity resonance, demonstrating that energy relaxation can be controlled on demand. Our results provide a general way to initialize spin systems into their ground state and therefore have applications in magnetic resonance and quantum information processing. They also demonstrate that the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point at which quantum fluctuations have a marked effect on the spin dynamics; as such, they represent an important step towards the coherent magnetic coupling of individual spins to microwave photons. PMID- 26878233 TI - Transient inhibition of ROR-gammat therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells. AB - RAR-related orphan receptor-gammat (ROR-gammat) directs differentiation of proinflammatory T helper 17 (TH17) cells and is a potential therapeutic target in chronic autoimmune and inflammatory diseases. However, ROR-gammat-dependent group 3 innate lymphoid cells ILC3s provide essential immunity and tissue protection in the intestine, suggesting that targeting ROR-gammat could also result in impaired host defense after infection or enhanced tissue damage. Here, we demonstrate that transient chemical inhibition of ROR-gammat in mice selectively reduces cytokine production from TH17 but not ILCs in the context of intestinal infection with Citrobacter rodentium, resulting in preserved innate immunity. Temporal deletion of Rorc (encoding ROR-gammat) in mature ILCs also did not impair cytokine response in the steady state or during infection. Finally, pharmacologic inhibition of ROR-gammat provided therapeutic benefit in mouse models of intestinal inflammation and reduced the frequency of TH17 cells but not ILCs isolated from primary intestinal samples of individuals with inflammatory bowel disease (IBD). Collectively, these results reveal differential requirements for ROR-gammat in the maintenance of TH17 cell and ILC3 responses and suggest that transient inhibition of ROR-gammat is a safe and effective therapeutic approach during intestinal inflammation. PMID- 26878232 TI - Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. AB - Impaired erythropoiesis in the deletion 5q (del(5q)) subtype of myelodysplastic syndrome (MDS) has been linked to heterozygous deletion of RPS14, which encodes the ribosomal protein small subunit 14. We generated mice with conditional inactivation of Rps14 and demonstrated an erythroid differentiation defect that is dependent on the tumor suppressor protein p53 (encoded by Trp53 in mice) and is characterized by apoptosis at the transition from polychromatic to orthochromatic erythroblasts. This defect resulted in age-dependent progressive anemia, megakaryocyte dysplasia and loss of hematopoietic stem cell (HSC) quiescence. As assessed by quantitative proteomics, mutant erythroblasts expressed higher levels of proteins involved in innate immune signaling, notably the heterodimeric S100 calcium-binding proteins S100a8 and S100a9. S100a8--whose expression was increased in mutant erythroblasts, monocytes and macrophages--is functionally involved in the erythroid defect caused by the Rps14 deletion, as addition of recombinant S100a8 was sufficient to induce a differentiation defect in wild-type erythroid cells, and genetic inactivation of S100a8 expression rescued the erythroid differentiation defect of Rps14-haploinsufficient HSCs. Our data link Rps14 haploinsufficiency in del(5q) MDS to activation of the innate immune system and induction of S100A8-S100A9 expression, leading to a p53 dependent erythroid differentiation defect. PMID- 26878236 TI - Evidence from cyclostomes for complex regionalization of the ancestral vertebrate brain. AB - The vertebrate brain is highly complex, but its evolutionary origin remains elusive. Because of the absence of certain developmental domains generally marked by the expression of regulatory genes, the embryonic brain of the lamprey, a jawless vertebrate, had been regarded as representing a less complex, ancestral state of the vertebrate brain. Specifically, the absence of a Hedgehog- and Nkx2.1-positive domain in the lamprey subpallium was thought to be similar to mouse mutants in which the suppression of Nkx2-1 leads to a loss of the medial ganglionic eminence. Here we show that the brain of the inshore hagfish (Eptatretus burgeri), another cyclostome group, develops domains equivalent to the medial ganglionic eminence and rhombic lip, resembling the gnathostome brain. Moreover, further investigation of lamprey larvae revealed that these domains are also present, ruling out the possibility of convergent evolution between hagfish and gnathostomes. Thus, brain regionalization as seen in crown gnathostomes is not an evolutionary innovation of this group, but dates back to the latest vertebrate ancestor before the divergence of cyclostomes and gnathostomes more than 500 million years ago. PMID- 26878237 TI - Stable amorphous georgeite as a precursor to a high-activity catalyst. AB - Copper and zinc form an important group of hydroxycarbonate minerals that include zincian malachite, aurichalcite, rosasite and the exceptionally rare and unstable -and hence little known and largely ignored--georgeite. The first three of these minerals are widely used as catalyst precursors for the industrially important methanol-synthesis and low-temperature water-gas shift (LTS) reactions, with the choice of precursor phase strongly influencing the activity of the final catalyst. The preferred phase is usually zincian malachite. This is prepared by a co-precipitation method that involves the transient formation of georgeite; with few exceptions it uses sodium carbonate as the carbonate source, but this also introduces sodium ions--a potential catalyst poison. Here we show that supercritical antisolvent (SAS) precipitation using carbon dioxide (refs 13, 14), a process that exploits the high diffusion rates and solvation power of supercritical carbon dioxide to rapidly expand and supersaturate solutions, can be used to prepare copper/zinc hydroxycarbonate precursors with low sodium content. These include stable georgeite, which we find to be a precursor to highly active methanol-synthesis and superior LTS catalysts. Our findings highlight the value of advanced synthesis methods in accessing unusual mineral phases, and show that there is room for exploring improvements to established industrial catalysts. PMID- 26878238 TI - Tumour-specific proline vulnerability uncovered by differential ribosome codon reading. AB - Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment. PMID- 26878239 TI - CENP-C directs a structural transition of CENP-A nucleosomes mainly through sliding of DNA gyres. AB - The histone H3 variant CENP-A is incorporated into nucleosomes that mark centromere location. We have recently reported that CENP-A nucleosomes, compared with their H3 counterparts, confer an altered nucleosome shape. Here, using a single-molecule fluorescence resonance energy transfer (FRET) approach with recombinant human histones and centromere DNA, we found that the nucleosome shape change directed by CENP-A is dominated by lateral passing of two DNA gyres (gyre sliding). A nonhistone centromere protein, CENP-C, binds and reshapes the nucleosome, sliding the DNA gyres back to positions similar to those in canonical nucleosomes containing conventional histone H3. The model that we generated to explain the CENP-A-nucleosome transition provides an example of a shape change imposed by external binding proteins and has notable implications for understanding of the epigenetic basis of the faithful inheritance of centromere location on chromosomes. PMID- 26878242 TI - Brasiliensic and isobrasiliensic acids: isolation from Calophyllum brasiliense Cambess. and anti-Helicobacter pylori activity. AB - The occurrence of chromanone derivatives has been noticed as a distinctive feature of the genus Calophyllum (Calophyllaceae). Previous studies have demonstrated that the extract of the stem bark of Calophyllum brasiliense and its chromanone-rich fractions show anti-ulcer activity in murine gastric ulcer models. In this work, brasiliensic and isobrasiliensic acids, the two main compounds of the n-hexane extract of the stem bark extract of C. brasiliense, were isolated by flash chromatography using silica gel impregnated with silver nitrate and their structures were elucidated by NMR techniques and mass spectrometry. 13C NMR data is available for the first time for both compounds. Brasiliensic and isobrasiliensic acids showed good in vitro bacteriostatic activity against Helicobacter pylori, and are responsible, at least in part, for the bacteriostatic anti-H. pylori activity of the n-hexane extract of the stem bark of C. brasiliense. PMID- 26878240 TI - 7SK-BAF axis controls pervasive transcription at enhancers. AB - RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA-damage signaling. 7SK physically interacts with the BAF chromatin-remodeling complex, recruits BAF to enhancers and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with that of Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK uses distinct mechanisms to counteract the diverse consequences of pervasive transcription that distinguish super enhancers, enhancers and promoters. PMID- 26878243 TI - Factors influencing pursuit of hearing evaluation: Enhancing the health belief model with perceived burden from hearing loss on communication partners. AB - OBJECTIVE: There is limited application of health behavior-based theoretical models in hearing healthcare, yet other fields utilizing these models have shown their value in affecting behavior change. The health belief model (HBM) has demonstrated appropriateness for hearing research. This study assessed factors that influence an individual with suspected hearing loss to pursue clinical evaluation, with a focus on perceived burden of hearing loss on communication partners, using the HBM as a framework. DESIGN: Cross-sectional design collecting demographics along with three validated hearing-loss related questionnaires. STUDY SAMPLE: Patients from Duke University Medical Center Otolaryngology Clinic aged 55-75 years who indicated a communication partner had expressed concern about their hearing. A final sample of 413 completed questionnaire sets was achieved. RESULTS: The HBM model construct 'cues to action' was a significant (p <0.001) predictor of pursuing hearing evaluation. Perceived burden of hearing loss on communication partners was a significant (p <0.001) predictor of pursuing hearing evaluation and improves the model fit when added to the HBM: 72.0% correct prediction when burden is added versus 66.6% when not (p <0.0001). CONCLUSIONS: Hearing healthcare initiatives that incorporate these factors may improve hearing help-seeking behavior. More research using sound theoretical models in hearing healthcare is warranted. PMID- 26878241 TI - Super-resolution 3D tomography of interactions and competition in the nuclear pore complex. AB - A selective barrier formed by intrinsically disordered Phe-Gly (FG) nucleoporins (Nups) allows transport receptor (TR)-facilitated translocation of signal dependent cargos through the nuclear pore complexes (NPCs) of eukaryotic cells. However, the configuration of the FG-Nup barrier and its interactions with multiple TRs in native NPCs remain obscure. Here, we mapped the interaction sites of various TRs or FG segments within the FG-Nup barrier by using high-speed super resolution microscopy and used these sites to reconstruct the three-dimensional tomography of the native barrier in the NPC. We found that each TR possesses a unique interaction zone within the FG-Nup barrier and that two major TRs, importin beta1 and Crm1, outcompete other TRs in binding FG Nups. Moreover, TRs may alter the tomography of the FG-Nup barrier and affect one another's pathways under circumstances of heavy competition. PMID- 26878244 TI - Clinical outcome in patients treated with simultaneous integrated boost - intensity modulated radiation therapy (SIB-IMRT) with and without concurrent chemotherapy for squamous cell carcinoma of the anal canal. AB - Background and purpose To retrospectively evaluate locoregional control (LRC), survival and toxicity in anal cancer patients treated with simultaneous integrated boost - intensity modulated radiation therapy (SIB-IMRT) +/- concurrent chemotherapy. Methods and materials Patients with squamous cell anal carcinoma stage T1(>=1 cm)-4, N0-3, M0-1 were included. All patients were treated with SIB-IMRT to a total dose of 59.4 Gy delivered to the primary tumor and macroscopically involved lymph nodes and 49.5 Gy to elective lymph node areas. If macroscopic residual tumor was still present in the fifth week of irradiation, a sequential boost of 5.4 Gy was given. Concurrent chemotherapy was administered in locally advanced cases. Acute and late toxicity were scored. Results One hundred and six patients treated consecutively between April 2006 and December 2012 were included. Eighty-seven (82.1%) patients received concurrent chemotherapy. The median follow-up was 47 months (range 2-104 months). Ninety-eight patients reached a clinical complete response (92.5%). Four-year actuarial LRC rate, overall survival and colostomy-free survival were 79%, 77% and 77%, respectively. Acute grade >=3 toxicity occurred in 67.9% of the patients. Late grade 3 toxicity was seen in 16 patients (15.1%). Conclusions SIB-IMRT +/- concurrent chemotherapy for anal cancer was effective with acceptable toxicity. PMID- 26878245 TI - Bouncing back again, and again: a qualitative study of resilience in people with multiple sclerosis. AB - Purpose The purpose of this study was to describe the meaning of resilience, factors facilitating resilience and barriers to resilience, from the perspective of persons with multiple sclerosis (MS), their care partners and community stakeholders. Method We conducted four focus groups: two with middle-aged (36-62 years) individuals with MS [one with men (n = 6) and one with women (n = 6)], one for partners of individuals with MS (n = 11) and one with community stakeholders serving people with MS (n = 9). We asked participants to describe what resilience means to them, what factors facilitate resilience and what barriers to resilience they perceive. We analyzed the focus group transcripts for emerging themes and sub-themes. Results Participants found it difficult to generate a concise definition of resilience, but they generated evocative descriptions of the concept. Psychological adaptation, social connection, life meaning, planning and physical wellness emerged as facilitators of resilience. Resilience depletion, negative thoughts and feelings, social limitations, social stigma and physical fatigue emerged as barriers to resilience. Conclusion The unpredictable nature of MS can present unique challenges to resilient adjustment, especially during middle age. However, several factors can contribute to resilience and quality of life, and these factors are amenable to intervention. Implications for Rehabilitation Resilience is the capacity to bounce back and thrive when faced with challenges. People with MS develop resilience through psychological adaptation, social connection, life meaning, planning ahead and physical wellness. Barriers to resilience with MS include burnout, negative thoughts and feelings, social difficulties, stigma and fatigue. Interventions should address both individual and social factors that support resilience, such as promoting positive thinking, planning and engagement in meaningful activities. PMID- 26878246 TI - A novel multimodality endoscopic device for colonic submucosal dissection using a combination of bipolar radiofrequency and microwave modalities. AB - BACKGROUND AND STUDY AIMS: Current submucosal dissection devices are technically challenging to use, resulting in long and sometimes incomplete colonic polyp resections. The aim of this feasibility preclinical study was to evaluate a new, multimodality instrument with novel electrocautery properties. METHODS: Six female adult pigs underwent colonic submucosal resections. The novel device was used to cut mucosa and submucosa using bipolar radiofrequency (BRF; at 400 KHz), provide hemostasis with microwave coagulation (MWC; at 5.8 GHz), and inject fluid via a retractable needle. The main outcomes measured were safety (histological analysis post-recovery), performance, and time needed to achieve complete resection. RESULTS: A total of 12 consecutive colonic pseudopolyps were completely excised (two per subject) using BRF cutting. The median time to complete resection was 44.3 minutes (SD 8.9). The median defect size was 32.8 mm (SD 4.3). MWC was applied on 37 occasions for pre-coagulation or treatment of bleeding vessels. One microperforation was treated successfully with endoscopic clips. All animals recovered uneventfully during the 28-day survival period. Histology confirmed adequate healing in all postmortem defects. CONCLUSIONS: In this preclinical evaluation, the novel multimodality endoscopic device facilitated rapid and safe en bloc resection of colonic pseudopolyps. PMID- 26878248 TI - Dissecting the Few-Femtosecond Dephasing Time of Dipole and Quadrupole Modes in Gold Nanoparticles Using Polarized Photoemission Electron Microscopy. AB - Dipole and quadrupole modes are the two lowest orders of localized surface plasmon resonance (LSPR) eigenmodes in metallic nanoparticles. Of these two modes, the quadrupole mode is forbidden for symmetric metallic nanoparticles excited by linearly polarized light at normal incidence. Here, we demonstrate excitation of the quadrupole mode in symmetrical gold (Au) nanoblocks shined with s-polarized light at oblique incidence. In particular, we probe the near-field LSPR in Au nanoblocks using photoemission electron microscopy (PEEM) and find that at oblique incidence, the dipole and quadrupole modes can be selectively excited, in terms of near-field enhancement, by manipulating the light polarization state. More importantly, by time-resolved PEEM measurements, we experimentally demonstrate that the quadrupole mode in symmetrical Au nanoblocks has longer dephasing time than that of the dipole mode. PMID- 26878247 TI - Dual-focus versus conventional magnification endoscopy for the diagnosis of superficial squamous neoplasms in the pharynx and esophagus: a randomized trial. AB - BACKGROUND AND STUDY AIMS: Conventional magnification narrow-band imaging (CM NBI) endoscopy has demonstrated high diagnostic accuracy for superficial squamous neoplasms in the pharynx and esophagus. This study aimed to evaluate the diagnostic utility of the newly developed dual-focus NBI (DF-NBI) compared with that of CM-NBI. PATIENTS AND METHODS: We recruited patients with squamous cell carcinoma (SCC) in the head and neck, or esophagus, or with a history of SCC. The primary endpoint of this prospective controlled non-inferiority trial was the sensitivity of DF-NBI and CM-NBI for detecting superficial carcinoma in the pharynx and esophagus. Secondary endpoints included other diagnostic values and the resolving power of each endoscope. Superficial carcinoma was defined as high grade dysplasia and SCC invading up to the submucosal layer. RESULTS: The study included 93 patients. A total of 28 superficial carcinomas were detected in the pharynx and esophagus. The sensitivities of DF-NBI and CM-NBI for superficial carcinoma were 82 % and 71 %, respectively. The lower limit of the 90 % confidence interval for the difference between the sensitivities exceeded the non inferiority threshold. The specificity and overall accuracy of DF-NBI vs. CM-NBI were 93 % vs. 90 % and 91 % vs. 86 %, respectively (both non-significant differences). The maximum resolving power of a conventional magnification endoscope was significantly higher than a dual-focus endoscope (7.2 um vs. 11.6 um: P < 0.001). CONCLUSIONS: The findings indicate the non-inferiority of DF-NBI versus CM-NBI in detecting superficial carcinoma in the pharynx and esophagus. DF NBI appears to have a resolving power that, although significantly lower, is sufficient to achieve high diagnostic accuracy, comparable to that of CM NBI.University Hospital Medical Information Network (UMIN, No. 000007585). PMID- 26878249 TI - Childhood CT scans and cancer risk: impact of predisposing factors for cancer on the risk estimates. AB - To investigate the role of cancer predisposing factors (PFs) on the associations between paediatric computed tomography (CT) scan exposures and subsequent risk of central nervous system (CNS) tumours and leukaemia. A cohort of children who underwent a CT scan in 2000-2010 in 23 French radiology departments was linked with the national childhood cancers registry and national vital status registry; information on PFs was retrieved through hospital discharge databases. In children without PF, hazard ratios of 1.07 (95% CI 0.99-1.10) for CNS tumours (15 cases) and 1.16 (95% CI 0.77-1.27) for leukaemia (12 cases) were estimated for each 10 mGy increment in CT x-rays organ doses. These estimates were similar to those obtained in the whole cohort. In children with PFs, no positive dose-risk association was observed, possibly related to earlier non-cancer mortality in this group. Our results suggest a modifying effect of PFs on CT-related cancer risks, but need to be confirmed by longer follow-up and other studies. PMID- 26878250 TI - Knee Dislocations and PCL-Based Multiligament Knee Injuries in Patients Aged 18 Years and Younger: Surgical Technique and Outcomes. AB - Knee dislocations and posterior cruciate ligament (PCL)-based multiple ligament knee injuries are complex injuries that can result in significant functional instability for the affected individual. The purpose of this article is to present a review of the literature, and the authors' experience treating knee dislocations and PCL-based multiple ligament knee injuries in patients 18 years of age and younger. This article will discuss patient age at the time of surgery, mechanisms of injury, surgical techniques, considerations in patients with open growth plates, a review of the literature, and the authors' surgical outcomes in these complex knee ligament instabilities. PMID- 26878251 TI - Abdominal obesity and gestational diabetes: the interactive role of magnesium. AB - AIMS: Magnesium is a cofactor for numerous metabolic enzymatic reactions. It is required for glucose utilization and insulin signaling. We compared plasma magnesium concentrations in pregnant women with and without abdominal obesity, and investigated the interactive roles of magnesium and obesity in the development of gestational diabetes mellitus (GDM). METHODS: Pregnant women with and without abdominal obesity (n = 40 in each group) were followed during gestation. Oral glucose tolerance tests (OGTT) were performed at 24-28 weeks of pregnancy to diagnose GDM. Plasma glucose, insulin, triglycerides, high-sensitive C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. The obesity GDM relationship was investigated prospectively, and the magnesium-GDM relationship was analyzed on a cross-sectional basis. RESULTS: Sixteen patients in the obese group and one in the control developed GDM. There were no differences in plasma magnesium levels between obese and control groups (p-value = 0.14), but significant differences between diabetic and non-diabetic patients (p-value = 0.05). Fourteen out of 17 diabetic patients had magnesium concentrations below the median. Increases in insulin, homeostatic model for insulin resistance, triglycerides, hs-CRP, MDA and second-hour blood glucose were more pronounced in those with both abdominal obesity and low-normal magnesium concentrations. In the Poisson regression model, obesity (relative risk = 20.6, p value = 0.002), low-normal magnesium level (relative risk = 4.2, p-value = 0.009), and their interaction (p-value<0.001) were significant. CONCLUSION: Abdominally obese patients with lower plasma magnesium are more likely to show abnormal OGTT results. Insulin resistance, inflammatory response and oxidative stress are exaggerated in these patients. PMID- 26878252 TI - Hyperphosphatemia, hypocalcemia and increased serum potassium concentration as distinctive features of early hypomagnesemia in magnesium-deprived mice. AB - Magnesium-deficient patients show dysfunctional calcium (Ca(2+)) metabolism due to defective parathyroid hormone (PTH) secretion. In mice and rats, long-term magnesium (Mg(2+)) deprivation causes hyperphosphaturia and increases fibroblast growth factor 23 (FGF23) secretion, despite normal serum phosphate (Pi) and Ca(2+). Electrolyte disturbances during early hypomagnesemia may explain the response of mice to long-term Mg(2+) deprivation, but our knowledge of electrolyte homeostasis during this stage is limited. This study compares the effect of both short- and long-term Mg(2+) restriction on the electrolyte balance in mice. Mice were fed control or Mg(2+)-deficient diets for one to three days, one week, or three weeks. Prior to killing the mice, urine was collected over 24 h using metabolic cages. Within 24 h of Mg(2+) deprivation, hypomagnesemia, hypocalcemia and hyperphosphatemia developed, and after three days of Mg(2+) deprivation, serum potassium (K(+)) was increased. These changes were accompanied by a reduction in urinary volume, hyperphosphaturia, hypocalciuria and decreased Mg(2+), sodium (Na(+)) and K(+) excretion. Surprisingly, after one week of Mg(2+) deprivation, serum K(+), Pi and Ca(2+) had normalized, showing that mineral homeostasis is most affected during early hypomagnesemia. Serum Pi and K(+) are known to stimulate secretion of FGF23 and aldosterone, which are usually elevated during Mg(2+) deficiency. Thus, the hyperphosphatemia and increased serum K(+) concentration observed during short-term Mg(2+) deprivation may help our understanding of adaptation to chronic Mg(2+) deficiency. PMID- 26878253 TI - An approach to the diagnosis and management of a case presenting with recurrent hypomagnesemia secondary to the chronic use of a proton pump inhibitor. AB - PURPOSE: Magnesium is an important electrolyte for very many cell functions and its deficiency may lead to a wide spectrum of diseases. We report a clinical case of hypomagnesemia resulting from the chronic use of a proton pump inhibitor (PPI). PPIs are drugs widely used in medical practice, and a growing number of cases of PPIs causing hypomagnesemia have been described. Our aim was to monitor the clinical and electrolyte findings during recovery from hypomagnesemia caused by long-term PPI use. RESULTS: A 65-year old female who had been using omeprazole for 10 years, presented with arrhythmia and paresthesia of the lower and upper limbs that had been attributed to severe hypomagnesemia, hypocalcemia, and hypoparathyroidism. Her laboratory tests revealed the following results: magnesium 0.6 mg/dL (NR: 1.5 to 2.5 mg/dL), calcium 7.3 mg/dL (NR: 8.5 to 10.2 mg/dL), parathyroid hormone (PTH) 13.3 pg/mL (NR: 15 to 65 pg/mL), and low urinary calcium and magnesium excretion. Her electrocardiogram disclosed typical, prolonged QT interval, ST depression, and U waves. We discuss the differential diagnoses, pathophysiology, and reversibility of symptoms after effective treatment of the hypomagnesemia. CONCLUSION: this report emphasizes that even if long-term PPI users appear largely asymptomatic, life-threatening arrhythmias can present very suddenly. Long-term PPI users should be monitored for otherwise unexplained hypomagnesemia, hypocalcemia, functional hypoparathyroidism and associated symptoms. PMID- 26878254 TI - Analytical studies on degradation mechanism of herbicide 4-chlorophenoxyacetic acid in water by gamma/H2O2 and gamma/ozone processes. AB - Radiolytic degradation of 4-chlorophenoxyacetic acid was followed in the presence of hydrogen peroxide and ozone. The synergic effect of ozone is found to be relatively high since the amounts of detected aromatic intermediates are lower as well as the amounts of small aliphatic acids are higher. Chloride ions are one of the most important mineralization products and splitted with a yield of more than 80%. The amounts of small aliphatic acids formed in the last step before mineralization (oxalic, acetic and formic acid) were followed and their formation from 4-chlorophenoxyacetic acid was confirmed. Dissolved oxygen was consumed to form reactive radicals during irradiation. Product analysis and confirmation are followed by gas chromatography/mass spectrometry and ion chromatography. The degradation path of 4-chlorophenoxyacetic acid was suggested with determined intermediates. PMID- 26878255 TI - Single-crystal nanopyramidal BGaN by nanoselective area growth on AlN/Si(111) and GaN templates. AB - We report nano-selective area growth (NSAG) of BGaN by MOCVD on AlN/Si(111) and GaN templates resulting in 150 nm single crystalline nanopyramids. This is in contrast to unmasked or micro-selective area growth, which results in a multi crystalline structure on both substrates. Various characterization techniques were used to evaluate NSAG as a viable technique to improve BGaN material quality on AlN/Si(111) using results of GaN NSAG and unmasked BGaN growth for comparison. Evaluation of BGaN nanopyramid quality, shape and size uniformity revealed that the growth mechanism is the same on both the templates. Further STEM analysis of BGaN nanopyramids on AlN/Si (111) templates confirmed that these are single crystalline structures without any dislocations, likely due to single nucleation occurring in the 80 nm mask opening. CL results correspond to boron content between 1.7% and 2.0% in the nanopyramids. We conclude that NSAG is promising for growth of high-quality BGaN nanostructures and complex nano-heterostructures, especially for low-cost silicon substrates. PMID- 26878256 TI - Electronic Flux Density beyond the Born-Oppenheimer Approximation. AB - In the Born-Oppenheimer approximation, the electronic wave function is typically real-valued and hence the electronic flux density (current density) seems to vanish. This is unfortunate for chemistry, because it precludes the possibility to monitor the electronic motion associated with the nuclear motion during chemical rearrangements from a Born-Oppenheimer simulation of the process. We study an electronic flux density obtained from a correction to the electronic wave function. This correction is derived via nuclear velocity perturbation theory applied in the framework of the exact factorization of electrons and nuclei. To compute the correction, only the ground state potential energy surface and the electronic wave function are needed. For a model system, we demonstrate that this electronic flux density approximates the true one very well, for coherent tunneling dynamics as well as for over-the-barrier scattering, and already for mass ratios between electrons and nuclei that are much larger than the true mass ratios. PMID- 26878257 TI - Comparative Effects of Different Balance-Training-Progression Styles on Postural Control and Ankle Force Production: A Randomized Controlled Trial. AB - CONTEXT: Despite the effectiveness of balance training, the exact parameters needed to maximize the benefits of such programs remain unknown. One such factor is how individuals should progress to higher levels of task difficulty within a balance-training program. Yet no investigators have directly compared different balance-training-progression styles. OBJECTIVE: To compare an error-based progression (ie, advance when proficient at a task) with a repetition-based progression (ie, advance after a set amount of repetitions) style during a balance-training program in healthy individuals. DESIGN: Randomized controlled trial. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 28 (16 women, 12 men) physically healthy young adults (age = 21.57 +/- 3.95 years, height = 171.60 +/- 11.03 cm, weight = 72.96 +/- 16.18 kg, body mass index = 24.53 +/- 3.7). INTERVENTION(S): All participants completed 12 supervised balance-training sessions over 4 weeks. Each session consisted of a combination of dynamic unstable-surface tasks that incorporated a BOSU ball and lasted about 30 minutes. MAIN OUTCOME MEASURE(S): Static balance from an instrumented force plate, dynamic balance as measured via the Star Excursion Balance Test, and ankle force production in all 4 cardinal planes of motion as measured with a handheld dynamometer before and after the intervention. RESULTS: Selected static postural control outcomes, dynamic postural control, and ankle force production in all planes of motion improved (P < .05). However, no differences between the progression styles were observed (P > .05) for any of the outcome measures. CONCLUSIONS: A 4-week balance-training program consisting of dynamic unstable surface exercises on a BOSU ball improved dynamic postural control and ankle force production in healthy young adults. These results suggest that an error based balance-training program is comparable with but not superior to a repetition-based balance-training program in improving postural control and ankle force production in healthy young adults. PMID- 26878258 TI - Postembryonic lineages of the Drosophila ventral nervous system: Neuroglian expression reveals the adult hemilineage associated fiber tracts in the adult thoracic neuromeres. AB - During larval life most of the thoracic neuroblasts (NBs) in Drosophila undergo a second phase of neurogenesis to generate adult-specific neurons that remain in an immature, developmentally stalled state until pupation. Using a combination of MARCM and immunostaining with a neurotactin antibody, Truman et al. (2004; Development 131:5167-5184) identified 24 adult-specific NB lineages within each thoracic hemineuromere of the larval ventral nervous system (VNS), but because of the neurotactin labeling of lineage tracts disappearing early in metamorphosis, they were unable extend the identification of these lineages into the adult. Here we show that immunostaining with an antibody against the cell adhesion molecule neuroglian reveals the same larval secondary lineage projections through metamorphosis and bfy identifying each neuroglian-positive tract at selected stages we have traced the larval hemilineage tracts for all three thoracic neuromeres through metamorphosis into the adult. To validate tract identifications we used the genetic toolkit developed by Harris et al. (2015; Elife 4) to preserve hemilineage-specific GAL4 expression patterns from larval into the adult stage. The immortalized expression proved a powerful confirmation of the analysis of the neuroglian scaffold. This work has enabled us to directly link the secondary, larval NB lineages to their adult counterparts. The data provide an anatomical framework that 1) makes it possible to assign most neurons to their parent lineage and 2) allows more precise definitions of the neuronal organization of the adult VNS based in developmental units/rules. J. Comp. Neurol. 524:2677-2695, 2016. (c) 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID- 26878259 TI - Cytosolic localization of NADH cytochrome b5 oxidoreductase (Ncb5or). AB - Acyl-CoA desaturation in the endoplasmic reticulum (ER) membrane depends on cytosolic NADH or NADPH, whereas NADPH in the ER lumen is utilized by prereceptor glucocorticoid production. It was assumed that NADH cytochrome b5 oxidoreductase (Ncb5or) might connect Acyl-CoA desaturation to ER luminal redox. We aimed to clarify the ambiguous compartmentalization of Ncb5or and test the possible effect of stearoyl-CoA on microsomal NADPH level. Amino acid sequence analysis, fluorescence microscopy of GFP-tagged protein, immunocytochemistry, and western blot analysis of subcellular fractions unequivocally demonstrated that Ncb5or, either endogenous or exogenous, is localized in the cytoplasm and not in the ER lumen in cultured cells and liver tissue. Moreover, the involvement of ER-luminal reducing equivalents in stearoyl-CoA desaturation was excluded. PMID- 26878260 TI - Accidental aspiration of denture cleanser tablets caused severe mucosal edema in upper airway. AB - A 78-year-old man accidentally swallowed denture cleanser tablets (Polident(r) ). Although he immediately spat them out, he felt difficulty in breathing. Observation using a fiber optic bronchoscope revealed a constricted glottis with edema and redness. The instillation of 1% xylocaine with epinephrine to the epiglottis and larynx reduced the edema and enabled the bronchoscope to pass the glottis. Red and edematous mucosa of the trachea and major bronchus were also observed. We should be aware that accidental aspiration of denture cleansers may cause laryngeal edema. PMID- 26878261 TI - "Cross" Supermicelles via the Hierarchical Assembly of Amphiphilic Cylindrical Triblock Comicelles. AB - Self-assembled "cross" architectures are well-known in biological systems (as illustrated by chromosomes, for example); however, comparable synthetic structures are extremely rare. Herein we report an in depth study of the hierarchical assembly of the amphiphilic cylindrical P-H-P triblock comicelles with polar (P) coronal ends and a hydrophobic (H) central periphery in a selective solvent for the terminal segments which allows access to "cross" supermicelles under certain conditions. Well-defined P-H-P triblock comicelles M(PFS-b-PtBA)-b-M(PFS-b-PDMS)-b-M(PFS-b-PtBA) (M = micelle segment, PFS = polyferrocenyldimethylsilane, PtBA = poly(tert-butyl acrylate), and PDMS = polydimethylsiloxane) were created by the living crystallization-driven self assembly (CDSA) method. By manipulating two factors in the supermicelles, namely the H segment-solvent interfacial energy (through the central H segment length, L1) and coronal steric effects (via the PtBA corona chain length in the P segment, L2 related to the degree of polymerization DP2) the aggregation of the triblock comicelles could be finely tuned. This allowed a phase-diagram to be constructed that can be extended to other triblock comicelles with different coronas on the central or end segment where "cross" supermicelles were exclusively formed under predicted conditions. Laser scanning confocal microscopy (LSCM) analysis of dye-labeled "cross" supermicelles, and block "cross" supermicelles formed by addition of a different unimer to the arm termini, provided complementary characterization to transmission electron microscopy (TEM) and dynamic light scattering (DLS) and confirmed the existence of these "cross" supermicelles as kinetically stable, micron-size colloidally stable structures in solution. PMID- 26878262 TI - Recent Progress on Bile Acid Receptor Modulators for Treatment of Metabolic Diseases. AB - Bile acids are steroid-derived molecules synthesized in the liver, secreted from hepatocytes into the bile canaliculi, and subsequently stored in the gall bladder. During the feeding, bile flows into the duodenum, where it contributes to the solubilization and digestion of lipid-soluble nutrients. After a meal, bile-acid levels increase in the intestine, liver, and also in the systemic circulation. Therefore, serum bile-acid levels serve as an important sensing mechanism for nutrient and energy. Recent studies have described bile acids as versatile signaling molecules endowed with systemic endocrine functions. Bile acids are ligands for G-protein coupled receptors (GPCRs) such as TGR5 (also known as GPBAR1, M-BAR, and BG37) and nuclear hormone receptors including farnesoid X receptor (FXR; also known as NR1H4). Acting through these diverse signaling pathways, bile acids regulate triglyceride, cholesterol, glucose homeostasis, and energy expenditure. These bile-acid-controlled signaling pathways have become the source of promising novel drug targets to treat common metabolic and hepatic diseases. PMID- 26878263 TI - Diffusion-weighted multiparametric MRI for monitoring longitudinal changes of parameters in rabbit VX2 liver tumors. AB - PURPOSE: To investigate the value of different quantitative models of diffusion weighted multiparametric imaging (DW-MPI) including traditional as well as several advanced models for monitoring the longitudinal parameter changes in rabbit liver VX2 carcinoma and for correlating the perfusion-related imaging parameters to vascularity of tumor tissue. MATERIALS AND METHODS: Rabbit liver VX2 carcinoma was imaged by DW-MPI at the 2nd, 3rd, and 4th weeks after tumor implantation at 1.5T using two sets of b values ranging from 0 to 2000 s/mm(2) . Serial parameter changes of each model at three timepoints were compared. Univariate and multivariate regression analyses were carried out to analyze the ability of perfusion-related parameters, including apparent diffusion coefficient (ADC), perfusion fraction (f), and pseudodiffusion coefficient (D*), to predict mean microvessel density (MVD) as determined by quantitative histopathology. RESULTS: For the period from Week 2 to Week 4, the measurements of ADC, f, and KDKI illustrated a statistical difference (P = 0.000, P = 0.000, and P = 0.002, respectively), whereas the comparison of D, D*, DDKI , DSEM , and alphaSEM demonstrated no statistical significance. ADC and f showed highest correlation with MVD at Week 4 (r(2) = 0.307, P = 0.017, and r(2) = 0.402, P < 0.01, respectively). Multivariate analyses confirmed highest correlation of f and ADC with MVD at Week 4 (P = 0.001 and P = 0.002). CONCLUSION: ADC, f, and KDKI were identified as the most promising parameters for monitoring changes in rabbit liver VX2 carcinoma and f and ADC showed highest correlation with MVD. J. Magn. Reson. Imaging 2016;44:707-714. PMID- 26878265 TI - Structural Flexibility and Conformation Features of Cyclic Dinucleotides in Aqueous Solutions. AB - Cyclic dinucleotides are able to trigger the innate immune system by activating STING. It was found that the binding affinity of asymmetric 2'3'-cGAMP to symmetric dimer of STING is 3 orders of magnitude higher than that of the symmetric 3'3'-cyclic dinucleotides. Such a phenomenon has not been understood yet. Here we show that the subtle changes in phosphodiester linkage of CDNs lead to their distinct structural properties which correspond to the varied binding affinities. 2'-5' and/or 3'-5' linked CDNs adopt specific while different types of ribose puckers and backbone conformations. That ribose conformations and base types have different propensities for anti or syn glycosidic conformations further affects the overall flexibility of CDNs. The counterbalance between backbone ring tension and electrostatic repulsion, both affected by the ring size, also contributes to the different flexibility of CDNs. Our calculations reveal that the free energy cost for 2'3'-cGAMP to adopt the STING-bound structure is smaller than that for 3'3'-cGAMP and cyclic-di-GMP. These findings may serve as a reference for design of CDN-analogues as vaccine adjuvants. Moreover, the cyclization pattern of CDNs closely related to their physiological roles suggests the importance of understanding structural properties in the study of protein-ligand interactions. PMID- 26878264 TI - Stabilizing interactions between D666-S1787 and T657-Y1792 at the A2-A3 interface support factor VIIIa stability in the blood clotting pathway. AB - Essentials Factor VIIIa (FVIIIa) is unstable due to loss of A2; D666 and Y1792 contribute to its stability. We conducted a study to identify the interactions made at these residues at the A2-A3 interface. We present evidence for stabilizing interactions between D666-S1787 and T657-Y1792 in FVIIIa. A D666C/S1788C variant with a disulfide A2-A3 linkage has a FVIIIa decay rate that is 1% of wild-type. SUMMARY: Background Factor (F)VIIIa activity and stability depends on the non-covalent association of the A2 subunit with the A1/A3C1C2 dimer, but the interactions that contribute to A2 association are not well defined. Previous work had shown that D666A and Y1792F mutations at the A2-A3 interface resulted in increased FVIIIa decay, suggesting that the residues were involved in bonding interactions important for FVIIIa stability. Objectives Several potential hydrogen bonding partners of D666 and Y1792 across the A2-A3 interface were selected from the low-resolution FVIII crystal structure, and we used mutagenesis and biochemical analysis to examine the bonding interactions occurring at D666 and Y1792. Methods Using a series of stability and functional analyses, we analyzed FVIII variants in which D666 and Y1792 were each swapped with the residues of potential bonding partners. Results and conclusions We present evidence for hydrogen bonds between D666 and S1787 and between Y1792 and T657 that are important for FVIIIa stability. D666S/S1787D and T657Y/Y1792T variants each displayed wild-type (WT)-like FVIIIa stability and performed like WT FVIII in a series of functional analyses, whereas D666S, S1787D, and Y1792T single variants showed increased FVIIIa decay and a T657Y variant had little FVIIIa activity. These results suggest that WT hydrogen bonds are disrupted with the single mutations but maintained in the swap variants. Furthermore, mutation of D666 and S1788 to cysteine resulted in disulfide bond formation across the A2 A3 interface, confirming the close proximity of D666 and S1787, and this covalent attachment of the A2 subunit significantly increased FVIIIa stability. PMID- 26878266 TI - Cross-sectional association between physical strength, obesity, periodontitis and number of teeth in a general population. AB - AIM: Muscle strength declines and gums recede with increasing age across the life course. Possible associations exist between handgrip strength as an indicator of physical fitness and periodontitis and number of teeth. MATERIAL AND METHODS: Handgrip strength (GS), anthropometric measures, clinical attachment loss, number of teeth, C-reactive protein and glycated haemoglobin were assessed in 2089 participants of the Study of Health in Pomerania (SHIP-2). Linear regression including interaction with age was used to estimate the association between clinical attachment level, number of teeth and GS. RESULTS: In multiple regression adjusted for age, body mass index (BMI) and waist-to-hip ratio (WHR) each mm of diminished periodontal attachment was associated with reduction in GS by 1.47 kg (95% CI -2.29 to -0.65) and 0.38 kg (-0.89 to 0.14) in men and women respectively. Correspondingly, each additional remaining tooth was significantly associated with higher GS. Using handgrip strength relative to BMI as outcome, these relationships become even more apparent. Indicators of obesity such as BMI and WHR associated with both GS and periodontitis modulate the relationship between GS and periodontitis with a different impact between the sexes. CONCLUSION: Periodontitis is associated with GS modified mainly by anthropometric measures related to adiposity and inflammation. Putative mechanisms encompass interactions of factors declining with increasing age. PMID- 26878268 TI - Development of rare resistance-associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two-hit mechanism. AB - AIM: The virologic characteristics of resistance-associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated. METHODS: A total of 206 patients with genotype-1b HCV infection, including 5 patients with previous simeprevir therapy, were treated with daclatasvir/asunaprevir for 24 weeks. Resistance-associated variants in the NS5A regions at baseline and during/after therapy were evaluated using cycling-probe real-time polymerase chain reaction combined with direct sequencing. The dynamics of rare RAVs were also assessed using ultra-deep sequencing. RESULTS: A sustained virologic response (SVR12) was achieved in 180 patients (87%); the rates were 95% in patients without baseline NS5A-RAVs and 83%, 59%, and 77% in those with hepatitis C virus (HCV) strains carrying NS5A-L31M, NS5A-Y93H/C, and NS5A R30Q/H/L mutations, respectively. A multivariate analysis revealed baseline NS5A R30Q/H/L mutation and NS5A-Y93H mutations as significant factors associated with SVR12. Virologic failure developed in all 5 patients with previous simeprevir treatment, and rare RAVs (HCV strains with NS5A-R30H, NS5A-A92K, NS5A-P29del, and NS5A-P32del) developed at virologic failure. Ultra-deep sequencing revealed that HCV strains with NS5A-P29del or NS5A-P32del were absent at baseline and emerged within 4 weeks of dual oral therapy among the strains appearing after simeprevir administration. CONCLUSION: NS5A-R30Q/H/L and NS5A-Y93H mutations at baseline determined the therapeutic efficacy of dual oral therapy with daclatasvir/asunaprevir, but rare NS5A-RAVs developed frequently in patients with previous simeprevir treatment. Such RAVs may develop in a two-hit manner, with simeprevir altering the quasispecies of HCV strains in the NS5A regions, leading to the emergence of HCV strains with NS5A-P29del and NS5A-P32del during exposure to daclatasvir/asunaprevir. PMID- 26878269 TI - Progesterone binding nano-carriers based on hydrophobically modified hyperbranched polyglycerols. AB - Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models. PMID- 26878267 TI - Community prevalence of long-term urinary catheters use in England. AB - OBJECTIVES: To calculate the prevalence of long term catheter use in the community in two areas in the south and west of England. SUBJECTS/PATIENTS (OR MATERIALS) AND METHODS: People in England register with general practices to access health care through a National Health Service. Catheters are provided by prescription free of charge. In 2008, patients using urinary catheters for over 3 months were identified, and demographic information collected, from databases of general practices, using catheter prescribing records. The age and sex distributions of people in each practice were obtained from capitation claims. Overall, and age and sex-specific prevalence were calculated separately for each area, and compared. RESULTS: A total of 583 long term catheter users (329 south, 254 west) were identified from 404,328 people registered with practices. The overall population prevalence is similar in both locations (0.146% southern, 0.141% western). Extrapolating for the United Kingdom, this is over 90,000 long term catheter users. Prevalence increases with age (0.732% in over 70 years, 1.224% over 80), especially amongst men. Overall, higher proportions have neurological (vs. non-neurological) reasons (62.9% vs. 37.1%) and use urethral (vs. suprapubic) catheters (59.7% vs. 40.3%). Compared to men, more women tend to use suprapubic (56.4% vs. 29.3%) and have a catheter for neurological reasons (71.8% vs. 56.2%, P = 0.053). CONCLUSIONS: Previous evidence on prevalence of long term catheter use is sparse, and of variable quality. The strength of this study is utilisation of a reliable source of data (catheter prescriptions) from a large population of patients. Neurourol. Urodynam. 36:293-296, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26878271 TI - Complexation of Ln(3+) Ions with Cyclam Dipicolinates: A Small Bridge that Makes Huge Differences in Structure, Equilibrium, and Kinetic Properties. AB - The coordination properties toward the lanthanide ions of two macrocyclic ligands based on a cyclam platform containing picolinate pendant arms have been investigated. The synthesis of the ligands was achieved by using the well-known bis-aminal chemistry. One of the cyclam derivatives (cb-tedpa(2-)) is reinforced with a cross-bridge unit, which results in exceptionally inert [Ln(cb-tedpa)](+) complexes. The X-ray structures of the [La(cb-tedpa)Cl], [Gd(cb-tedpa)](+), and [Lu(Me2tedpa)](+) complexes indicate octadentate binding of the ligands to the metal ions. The analysis of the Yb(3+)-induced shifts in [Yb(Me2tedpa)](+) indicates that this complex presents a solution structure very similar to that observed in the solid state for the Lu(3+) analogue. The X-ray structures of [La(H2Me2tedpa)2](3+) and [Yb(H2Me2tedpa)2](3+) complexes confirm the exocyclic coordination of the metal ions, which gives rise to coordination polymers with the metal coordination environment being fulfilled by oxygen atoms of the picolinate groups and water molecules. The X-ray structure of [Gd(Hcb-tedpa)2](+) also indicates exocyclic coordination that in this case results in a discrete structure with an eight-coordinated metal ion. The nonreinforced complexes [Ln(Me2tedpa)](+) were prepared and isolated as chloride salts in nonaqueous media. However, these complexes were found to undergo dissociation in aqueous solution, except in the case of the complexes with the smallest Ln(3+) ions (Ln(3+) = Yb(3+) and Lu(3+)). A DFT investigation shows that the increased stability of the [Ln(Me2tedpa)](+) complexes in solution across the lanthanide series is the result of an increased binding energy of the ligand due to the increased charge density of the Ln(3+) ion. PMID- 26878270 TI - Isosteric and fluorescent DNA base pair formed by 4-amino-phthalimide and 2,4 diaminopyrimidine: melting, structure, and THz polar solvation dynamics. AB - An artificial base pair in the center of a duplex DNA oligomer, formed by 2,4 diaminopyrimidine and fluorescent 4-aminophthalimide C-nucleosides, is characterized spectroscopically, with a view towards its use in femtosecond solvation dynamics. Quantum-chemical calculations predict H-bonding energy equivalent to A:T. UV-vis absorption spectra provide insight into local melting at the 4-aminophthalimide modification site. Increase of temperature to nearly the melting temperature of the duplex leads to better hybridisation of the fluorescent nucleoside, contrary to native base pairs. This unusual observation is explained by the NMR solution structure of the duplex. Two conformations are adopted by the artificial pair due to backbone constraints, having either two or one interbase hydrogen bonds. In the latter, hydrogen bonding sites remain accessible for water solvation. The time-resolved dynamic Stokes' shift of 4 aminophthalimide fluorescence is consistent with that of a mixture of a slow and fast species. From the observations, the optimal linkage between 4 aminophthalimide and 2-deoxyribose for fitting into the duplex B-DNA structure is deduced. PMID- 26878273 TI - Carbon dioxide reduction on Ir(111): stable hydrocarbon surface species at near ambient pressure. AB - Stable hydrocarbon surface species in the carbon dioxide hydrogenation reaction on Ir(111) were identified by means of infrared-visible sum-frequency generation vibrational spectroscopy and X-ray photoelectron spectroscopy under near-ambient pressure conditions (0.1 mbar). By introducing gas phase binary and ternary mixtures of CO2, CO, and H2 into the reaction chamber, stable ethylidyne and ethynyl species were found at the metal surface above 425 K, in remarkable analogy with that observed during the ethylene decomposition process yielding graphene. In addition, upon increasing temperature (up to 600 K depending on the reaction conditions), vibrational and electronic spectroscopic fingerprints appeared that could be attributed to the nucleation of aromatic hydrocarbons at the edge of metastable graphenic clusters interacting with the metal surface. PMID- 26878274 TI - The effect of the nanosize on surface properties of NiO nanoparticles for the adsorption of Quinolin-65. AB - Using Quinolin-65 (Q-65) as a model-adsorbing compound for polar heavy hydrocarbons, the nanosize effect of NiO nanoparticles on the adsorption of Q-65 was investigated. Different-sized NiO nanoparticles with sizes between 5 and 80 nm were prepared by the controlled thermal dehydroxylation of Ni(OH)2. The properties of the nanoparticles were characterized using XRD, BET, FTIR, HRTEM and TGA. The effects of the nanosize on the textural properties, the shape and the morphology were studied. The adsorption of Q-65 molecules onto different sized nanoparticles was tested in toluene-based solutions. On a normalized surface area basis, the number of Q-65 molecules adsorbed per nm(2) of the NiO surface was the highest for NiO nanoparticles of size 80 nm, while that for 5 nm sized NiO nanoparticles was the lowest. Excitingly, the adsorption capacity of other NiO sizes varied from loading suggesting different adsorption behavior, which exhibits the significance of textural properties during the adsorption of Q 65. Computational modeling of the interaction between the Q-65 molecule and the NiO nanoparticle surface was carried out to get more understanding of its adsorption behavior. A number of factors contributing to the enhanced adsorption capacity of nanoscale NiO were determined. These include surface reactivity, topology, morphology and textural properties. PMID- 26878277 TI - Substrate and pH-Dependent Kinetic Profile of 3-Mercaptopropionate Dioxygenase from Pseudomonas aeruginosa. AB - Thiol dioxygenases catalyze the synthesis of sulfinic acids in a range of organisms from bacteria to mammals. A thiol dioxygenase from the bacterium Pseudomonas aeruginosa oxidizes both 3-mercaptopropionic acid and cysteine, with a ~70 fold preference for 3-mercaptopropionic acid over all pHs. This substrate reactivity is widened compared to other thiol dioxygenases and was exploited in this investigation of the residues important for activity. A simple model incorporating two protonation events was used to fit profiles of the Michaelis Menten parameters determined at different pH values for both substrates. The pKs determined using plots of k(cat)/Km differ at low pH, but not in a way easily attributable to protonation of the substrate alone and share a common value at higher pH. Plots of k(cat) versus pH are also quite different at low pH showing the monoprotonated ES complexes with 3-mercaptopropionic acid and cysteine have different pKs. At higher pH, k(cat) decreases sigmoidally with a similar pK regardless of substrate. Loss of reactivity at high pH is attributed to deprotonation of tyrosine 159 and its influence on dioxygen binding. A mechanism is proposed by which deprotonation of tyrosine 159 both blocks oxygen binding and concomitantly promotes cystine formation. Finally, the role of tyrosine 159 was further probed by production of a G95C variant that is able to form a cysteine tyrosine crosslink homologous to that found in mammalian cysteine dioxygenases. Activity of this variant is severely impaired. Crystallography shows that when un crosslinked, the cysteine thiol excludes tyrosine 159 from its native position, while kinetic analysis shows that the thioether bond impairs reactivity of the crosslinked form. PMID- 26878278 TI - Spontaneous defects between the mastoid and posterior cranial fossa. AB - Conclusions Spontaneous defects between the mastoid and the posterior cranial fossa are exceedingly rare. Patients with these lesions may have a lower BMI compared to those with middle cranial fossa encephaloceles, but are otherwise demographically similar. This study recommends repair via a transtemporal approach to allow for examination of the entire posterior face of the temporal bone. Objective To describe cases of spontaneous posterior cranial fossa defects. Methods This study reviewed all cases of spontaneous posterior fossa defects presenting to a tertiary referral center over the last decade and described clinical presentation, imaging, operative findings, and outcomes. We also compared these lesions to those previously reported in the literature as well as the more common spontaneous encephaloceles of the middle cranial fossa. Results This study identified five cases with a mean age of 61.4 years, female-to-male ratio of 4:1, and a mean BMI of 31. Three cases presented with spontaneous pneumocephalus, one with CSF otorrhea, and one as an incidental imaging finding. Four defects were found medial to the sigmoid sinus and one was in the lateral retrosigmoid air cells. PMID- 26878279 TI - Concentration of Sindbis virus with optimized gradient insulator-based dielectrophoresis. AB - Biotechnology, separation science, and clinical research are impacted by microfluidic devices. Separation and manipulation of bioparticles such as DNA, protein and viruses are performed on these platforms. Microfluidic systems provide many attractive features, including small sample size, rapid detection, high sensitivity and short processing time. Dielectrophoresis (DEP) and electrophoresis are especially well suited to microscale bioparticle control and have been demonstrated in many formats. In this work, an optimized gradient insulator-based DEP device was utilized for concentration of Sindbis virus, an animal virus with a diameter of 68 nm. Within only a few seconds, the concentration of Sindbis virus can be increased by two to six times in the channel under easily accessible voltages as low as about 70 V. Compared with traditional diagnostic methods used in virology, DEP-based microfluidics can enable faster isolation, detection and concentration of viruses in a single step within a short time. PMID- 26878275 TI - Contrasting cardiovascular mortality trends in Eastern Mediterranean populations: Contributions from risk factor changes and treatments. AB - BACKGROUND: Middle income countries are facing an epidemic of non-communicable diseases, especially coronary heart disease (CHD). We used a validated CHD mortality model (IMPACT) to explain recent trends in Tunisia, Syria, the occupied Palestinian territory (oPt) and Turkey. METHODS: Data on populations, mortality, patient numbers, treatments and risk factor trends from national and local surveys in each country were collated over two time points (1995-97; 2006-09); integrated and analysed using the IMPACT model. RESULTS: Risk factor trends: Smoking prevalence was high in men, persisting in Syria but decreasing in Tunisia, oPt and Turkey. BMI rose by 1-2 kg/m(2) and diabetes prevalence increased by 40%-50%. Mean systolic blood pressure and cholesterol levels increased in Tunisia and Syria. Mortality trends: Age-standardised CHD mortality rates rose by 20% in Tunisia and 62% in Syria. Much of this increase (79% and 72% respectively) was attributed to adverse trends in major risk factors, occurring despite some improvements in treatment uptake. CHD mortality rates fell by 17% in oPt and by 25% in Turkey, with risk factor changes accounting for around 46% and 30% of this reduction respectively. Increased uptake of community treatments (drug treatments for chronic angina, heart failure, hypertension and secondary prevention after a cardiac event) accounted for most of the remainder. DISCUSSION: CHD death rates are rising in Tunisia and Syria, whilst oPt and Turkey demonstrate clear falls, reflecting improvements in major risk factors with contributions from medical treatments. However, smoking prevalence remains very high in men; obesity and diabetes levels are rising dramatically. PMID- 26878280 TI - Aluminum trichloride inhibits osteoblastic differentiation through inactivation of Wnt/beta-catenin signaling pathway in rat osteoblasts. AB - Exposure to aluminum (Al) suppresses bone formation. Osteoblastic differentiation plays a key role in the process of bone formation. However, the effect of Al on osteoblastic differentiation is still controversial, and the mechanism remains unclear. To investigate the effect of Al on osteoblastic differentiation and whether Wnt signaling pathway was involved in it, the primary rat osteoblasts were exposed to 1/40 IC50, 1/20 IC50 and 1/10 IC50 of aluminum trichloride (AlCl3) for 24h, respectively. The activity analysis of alkaline phosphate, qRT PCR analysis of type I collagen, alkaline phosphate, Wnt3a and Dkk-1, Western blot analysis of p-GSK3beta, GSK3beta and beta-catenin protein and Immunofluorescence staining for beta-catenin suggested that AlCl3 inhibited osteoblastic differentiation and Wnt/beta-catenin pathway. Moreover, we found exogenous Wnt3a application reversed the inhibitory effect of AlCl3 on osteoblastic differentiation, accompanied by activating the Wnt/beta-catenin pathway. Taken together, these findings suggest that AlCl3 inhibites osteoblastic differentiation through inactivation of Wnt/beta-catenin pathway in osteoblasts. PMID- 26878281 TI - Paraquat inhibited differentiation in human neural progenitor cells (hNPCs) and down regulated miR-200a expression by targeting CTNNB1. AB - Paraquat (PQ) exposure influences central nervous system and results in serious neurotoxicity in vitro and in vivo. However, the role of PQ exposure in the development of CNS remains unclear. In present study, we investigated microRNAs (miRNAs) expression profiling and cell differential status following PQ treatment in human neural progenitor cells (hNPCs) as well as involved mechanism. Microarray profiling of miRNAs expression of PQ treated cell line and their corresponding control was determined. Differentially expression miRNAs were confirmed by quantitative real time PCR. Neural cell differentiation was performed with immunocytochemical analysis. Predicated target of miRNA was identified with luciferase reports and quantitatively analyzed using western blotting. Our results found PQ dramatically suppressed neural cell differentiation ability. 43 differentially expressed miRNAs were identified in PQ treated cells. The expression levels were over expressed in 25 miRNAs, whereas 18 miRNAs were suppressed. More importantly, we observed that miR-200a expression level to be lower in PQ treated cells. Luciferase assay and protein expression results confirmed the direct binding effect between CTNNB1 and miR-200a following PQ exposure. Collectively, our data suggested that down regulation of miR-200a in the PQ treated neural stem cell significantly participated in the differentiation processes and subsequently resulting in decreased cell viability, increased epithelial-mesenchymal transition process and the inhibited differential through CTNNB1 pathway. PMID- 26878282 TI - The association of urinary polycyclic aromatic hydrocarbon biomarkers and cardiovascular disease in the US population. AB - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants produced by incomplete combustion of organic materials. Pre-clinical and occupational studies have reported a positive association of PAHs with oxidative stress, inflammation and subsequent development of atherosclerosis, a major underlying risk factor for cardiovascular disease (CVD). The aim of the current study is to estimate the association between levels of PAH biomarkers and CVD in a national representative sample of United States (US) adults. METHODS: We examined adult participants (>=20years of age) from the merged US National Health and Nutrition Examination Survey 2001-2010. Logistic regression models were used to estimate the associations of each urinary PAH biomarker and CVD. Post exploratory structural equation modeling was then used to address the interdependent response variables (angina, heart attack, stroke and coronary heart disease) as well as the interdependencies of PAH biomarkers. RESULTS: PAH biomarkers were positively associated with cardiovascular disease in multiple logistic regression models, although some associations were not statistically robust. Using structural equation modeling, latent PAH exposure variable was positively associated with latent CVD level variable in the multivariable adjusted model (beta=0.12; 95% CI: 0.03, 0.20). CONCLUSION: A modest association between levels of PAH biomarkers and CVD was detected in US adults. Further prospective studies with adequate sample size are needed to replicate or refute our findings. PMID- 26878283 TI - Association between background exposure to organochlorine pesticides and the risk of cognitive impairment: A prospective study that accounts for weight change. AB - BACKGROUND: Background exposure to organochlorine (OC) pesticides was recently linked to cognitive impairment and dementia in cross-sectional and case-control studies. This prospective study was performed to evaluate if OC pesticides at baseline are associated with the future risk of cognitive impairment in elderly, with particular focus on weight change. METHODS: Plasma concentrations of 3 OC pesticides (p,p'-DDE, trans-nonachlor, and hexachlorobenzene) were measured among 989 men and women aged 70years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). Cognitive impairment was validated by reviewing medical records. During the ten year follow-up, cognitive impairment was developed in 75 subjects. When weight change from age 70 to 75 was considered in analyses, elderly with incident cases before age 75 were excluded to keep the prospective perspective, leaving 795 study subjects and 44 incident cases. RESULTS: The summary measure of 3 OC pesticides predicted the development of cognitive impairment after adjusting for covariates, including weight change. Compared to subjects with OC pesticides <25th percentile, adjusted hazard ratios (HRs) in those with 25th-<75th and >=75th percentiles were 3.5 (95% confidence interval: 1.5-8.5) and 3.2 (1.1-7.6), respectively (Ptrend=0.04). Among 506 subjects who maintained or gained body weight, adjusted HRs were 6.9 and 11.6 (1.4-92.6) among the elderly in the 25th-<75th and >=75th percentiles compared to <25th percentile (Ptrend<0.01). CONCLUSIONS: This prospective study demonstrates that background exposure to OC pesticides are linked to the risk of developing cognitive impairment in elderly. The role of the chronic exposure to low dose OC pesticides in the development of dementia should be further evaluated in other populations. PMID- 26878285 TI - Impact of heatwave on mortality under different heatwave definitions: A systematic review and meta-analysis. AB - Heatwave effects on human health and wellbeing is a great public health concern, especially in the context of climate change. However, no universally consistent heatwave definition is available. A systematic review and meta-analysis was conducted to assess the heatwave definitions used in the literature published up to 1st April 2015 by searching five databases (PubMed, ProQuest, ScienceDirect, Scopus, and Web of Science). Random-effects models were used to pool the effects of heatwave on total and cardiorespiratory mortality by different heatwave definitions. Existing evidence suggests a significant impact of heatwave on mortality, but the magnitude of the effect estimates varies under different heatwave definitions. Heatwave-related mortality risks increased by 4% (using "mean temperatures >=95th percentile for >=2days" as a heatwave definition), 3% (mean temperatures >=98th percentile for >=2days), 7% (mean temperatures >=99th percentile for >=2days) and 16% (mean temperatures >=97th percentile for >=5days). Heatwave intensity plays a relatively more important role than duration in determining heatwave-related deaths. Heatwaves significantly increase mortality across the globe, but the effect estimates vary with the definition of heatwaves. City- or region-specific heat health early warning systems based on identified local heatwave definitions may be optimal for protecting and preventing people from the adverse impacts of future heatwaves. PMID- 26878286 TI - Morphological and nanostructural surface changes in Escherichia coli over time, monitored by atomic force microscopy. AB - The present study aims at evaluating intrinsic changes in Escherichia coli (E. coli) surface over time, by Atomic Force Microscopy (AFM). For that purpose, bacteria were immobilized on mica or on mica previously functionalized by the deposition of a polyelectrolyte multilayer cushion. AFM images reveal that E. coli population goes through different stages. Firstly, after a week, the number of healthy bacteria decreases resulting in a release of cellular components which likely become, in turn, a nutrition source for increasing the healthy population after around two weeks. Finally, after one month, most of the bacteria is dead. Our study shows a transition of a healthy rod-shaped bacterium to a dead collapsed one. Most importantly, along with the morphological evolution of bacteria, are the structure changes and the mechanical properties of their outer membrane, emphasized by AFM phase images with very high resolution. Indeed, the surface of healthy bacteria is characterized by a phase separation pattern, thereafter mentioned as "ripples". Bacterial ageing goes along with the loss of this organized structure, turning into circular areas with irregular boundaries. These changes are likely caused by a re-organization, due to external stress, of mainly lipopolysaccharides (LPS) present in the outer membrane of E. coli. PMID- 26878284 TI - Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence. AB - BACKGROUND: Despite studies having consistently linked exposure to single-source polycyclic aromatic hydrocarbons (PAHs) to breast cancer, it is unclear whether single sources or specific groups of PAH sources should be targeted for breast cancer risk reduction. OBJECTIVES: This study considers the impact on breast cancer incidence from multiple PAH exposure sources in a single model, which better reflects exposure to these complex mixtures. METHODS: In a population based case-control study conducted on Long Island, New York (N=1508 breast cancer cases/1556 controls), a Bayesian hierarchical regression approach was used to estimate adjusted posterior means and credible intervals (CrI) for the adjusted odds ratios (ORs) for PAH exposure sources, considered singly and as groups: active smoking; residential environmental tobacco smoke (ETS); indoor and outdoor air pollution; and grilled/smoked meat intake. RESULTS: Most women were exposed to PAHs from multiple sources, and the most common included active/passive smoking and grilled/smoked food intake. In multiple-PAH source models, breast cancer incidence was associated with residential ETS from a spouse (OR=1.20, 95%CrI=1.03, 1.40) and synthetic firelog burning (OR=1.29, 95%CrI=1.06, 1.57); these estimates are similar, but slightly attenuated, to those from single-source models. Additionally when we considered PAH exposure groups, the most pronounced significant associations included total indoor sources (active smoking, ETS from spouse, grilled/smoked meat intake, stove/fireplace use, OR=1.45, 95%CrI=1.02, 2.04). CONCLUSIONS: Groups of PAH sources, particularly indoor sources, were associated with a 30-50% increase in breast cancer incidence. PAH exposure is ubiquitous and a potentially modifiable breast cancer risk factor. PMID- 26878288 TI - Contribution of carboxyl modified chiral mesoporous silica nanoparticles in delivering doxorubicin hydrochloride in vitro: pH-response controlled release, enhanced drug cellular uptake and cytotoxicity. AB - In this study, dual functionalized mesoporous silica nanoparticle (Dual-MSN) with functions of carboxyl modification and chirality was successfully developed and its special contribution in delivering doxorubicin hydrochloride (DOX) in vitro was mainly studied. Characteristics of Dual-MSN and its application as DOX carrier were intensively explored by comparing with naked non-functionalized MSN (Naked MSN). The results indicated that both Naked MSN and Dual-MSN significantly controlled DOX release due to the release hindrance caused by mesopores. As expected, Dual-MSN exhibited obvious enhanced pH-response because of its negative charges of carboxyl groups. DOX loaded Naked MSN and DOX loaded Dual-MSN presented better cytotoxicity than DOX due to carrier-mediated endocytosis and the favorable intercalation of DOX into DNA in the nuclei. The cytotoxicity of DOX loaded Dual-MSN was better than DOX loaded Naked MSN owing to its enhanced cellular uptake induced by chirality of Dual-MSN, demonstrating that double functions of Dual-MSN had unique advantages in improving antitumor effect of DOX towards MCF-7 cells and thus confirming its special contribution in DOX delivery. PMID- 26878287 TI - The effects of plasma electrolytically oxidized NiTi on in vitro endothelialization. AB - The role of biomaterials surface in controlling the interfacial biological events leading to implant integration is of key importance. In this study, the effects of NiTi surfaces treated by plasma electrolytic oxidation (PEO) on human umbilical vein endothelial cells (HUVECs) have been investigated. The changes in NiTi surface morphology and chemistry were assessed by SEM, XPS and cross-section TEM/EDX analyzes whereas the effects of the resultant surfaces on in vitro endothelialization and cell junction proteins have been evaluated by life/dead staining, SEM, cells counting, qPCR and immunofluorescence. The findings indicated that the PEO-treated NiTi, with a microporous morphology and oxide dominated surface chemistry, supports viability and proliferation of HUVECs. Numerous thin filopodia probing the microporous surface assisted cells attachment. In addition, claudin-5 and occludin have been upregulated and expression of vascular endothelial-cadherin was not suppressed on PEO-treated NiTi relative to the reference electropolished surfaces. The results of this study suggest that novel NiTi surfaces may be developed using the PEO process, which can be of benefit to atherosclerosis treatment. PMID- 26878289 TI - Magnetoconductive maghemite core/polyaniline shell nanoparticles: Physico chemical and biological assessment. AB - Nanoparticles of various compositions are increasingly being used in many areas of medicine. The aim of this study was to develop nanoparticles, which would possess both magnetic and conductive properties and, thus improve their suitability for a wider range of biomedical applications. Namely, it would enable both the particle manipulation and imaging using their magnetic properties and simultaneous stimulation of electro-sensitive cell types using their magnetic properties, which can be used in tissue therapy, engineering and as biosensors. Maghemite (gamma-Fe2O3) particles were prepared by the co-precipitation of Fe(2+) and Fe(3+) salts with ammonium hydroxide, followed by the controlled oxidation with NaOCl. The polyaniline (PANI) shell on the gamma-Fe2O3 nanoparticles was obtained by the polymerization of aniline hydrochloride with ammonium peroxydisulfate in an aqueous solution of poly(N-vinylpyrrolidone) at two reaction temperatures (0 and 25 degrees C). The resulting gamma-Fe2O3&PANI particles were characterized by both the light and transmission electron microscopies, dynamic light scattering, magnetic measurements, UV-vis and energy dispersive X-ray (EDAX) spectroscopy. The size of the starting gamma-Fe2O3 particles was 11 nm, that increased to 25 nm after the modification with PANI. The incubation of both the gamma-Fe2O3 and gamma-Fe2O3&PANI nanoparticles with the human neuroblastoma derived SH-SY5Y cells for 8 days showed neither significant decrease in the cell viability, nor detectable changes in the cell morphology. This indicates, that the particles have no detectable cytotoxicity in cell culture and represent a promising tool for further use in biomedical applications. PMID- 26878290 TI - Dielectric spectroscopy study of water dynamics in frozen bovine milk. AB - Bovine milk is a complex colloidal liquid exhibiting a multi-scaled structure. It is of particular importance, both commercially and scientifically, to investigate both its dynamic and structural properties. In the current study we have employed the broadband dielectric spectroscopy (BDS) technique in the frequency range of 10(-1)-10(6)Hz and the temperature range of 176-230 K in order to examine the molecular structure and dynamics of quenched bovine milk. Four dielectric relaxation processes were identified. Three of them are associated with water in its different forms: water-lactose complexes, bulk hexagonal and cubic ices. The fourth process is attributed to domain wall relaxations linked to the presence of micro-cracks in the ice structures. In addition, the first process, attributed to water-lactose complexes, obeys the Meyer-Neldel compensation law and can be taken as evidence of differing interfaces of these complexes with the bulk water of the milk, mediated by the lactose concentration. Furthermore, an intriguing structural-dynamic transition around 200K was observed. Considering the mentioned above, we conclude that our results emphasize the structural and dynamical significance of water in bovine milk. PMID- 26878291 TI - Significance of multimodal intraoperative monitoring for the posterior cervical spine surgery. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of multimodal neurophysiologic intra-operative monitoring (IOM) in a cohort of patients who underwent posterior cervical surgery. MATERIAL AND METHODS: A total 182 patients were included in this study. Multi-modal intraoperative monitoring (MIOM, somatosensory-evoked potentials: SSEP/transcranial motor-evoked potentials: TCe MEP/spontaneous-electromyography: S-EMG) was performed in a consecutive series of 129 patients and the other 53 patients (control group) did not. We classified all patients into a high-cervical (H-C) operation group or a low-cervical (L-C) operation group, based on the level of the surgery and analyzed respectively. RESULTS: One hundred-eleven cases (86%) showed true negative results. Fourteen patients (9 cases- H-C operation, 5 cases- L-C operation) met the criteria of neurophysiologic changes during operation. Of these, 10 cases were restored to normal during operation spontaneously (7 cases) or with surgical manipulation (all 3 cases were related to H-C operation). All unrestored neurophysiologic cases (n=4) showed new post-operative neurological deficits. Four patients showed neurological deficits without any changes in MIOM (false negative, 3 cases- delayed onset C5 palsy, 1 case--C8 palsy). CONCLUSIONS: Proper application of MIOM may be useful to detect intraoperative neurological injury during the posterior cervical operations and improve surgical outcomes especially in subgroup of H-C operation. However, the efficacy of MIOM may be restricted to detect and prevent the delayed onset C5 palsy. PMID- 26878292 TI - Adjacent segment degeneration after posterior lumbar fusion: An analysis of possible risk factors. AB - OBJECTIVE: Many surveys have been distributed about the risk factors for adjacent segment degeneration (ASD) after lumbar fusion. Despite myriad of risk factors recognized for ASD evolution, study results have been inconsistent and there is not an agreement regarding which are the most important. Our study was done to identify factors which may be important in the development of symptomatic ASD after lumbar fusion. PATIENTS AND METHODS: This retrospective study evaluated 1250 consecutive patients who underwent posterior lumbar fusion and pedicular fixation between February 2006 and February 2009. A total of 13 patients with symptomatic ASD (clinical ASD) who underwent secondary surgery were identified. Another group of 22 patients without symptomatic ASD (subclinical ASD) after spinal fusion were marked as the control group. These two groups were compared for demographic data and clinical and radiographic features to investigate the possible predictive factors of symptomatic ASD. RESULTS: The overall incidence rate of symptomatic ASD was 1.04%. Radiographic risk factors for the development of a symptomatic ASD were increased sagittal balance, loss of lordosis, and adjacent disc space collapse. In the clinical ASD group, by multivariate logistic regression analysis, demonstrated that BMI, preoperative ADD on MRI and disc bulge maintained their significance in predicting likelihood of clinical ASD. CONCLUSION: Patients with increased BMI, preoperative ADD and disc bulge on MRI have a statistically significant increased risk of developing symptomatic ASD. PMID- 26878293 TI - The influence of cell morphology on the compressive fatigue behavior of Ti-6Al-4V meshes fabricated by electron beam melting. AB - Additive manufacturing technique is a promising approach for fabricating cellular bone substitutes such as trabecular and cortical bones because of the ability to adjust process parameters to fabricate different shapes and inner structures. Considering the long term safe application in human body, the metallic cellular implants are expected to exhibit superior fatigue property. The objective of the study was to study the influence of cell shape on the compressive fatigue behavior of Ti-6Al-4V mesh arrays fabricated by electron beam melting. The results indicated that the underlying fatigue mechanism for the three kinds of meshes (cubic, G7 and rhombic dodecahedron) is the interaction of cyclic ratcheting and fatigue crack growth on the struts, which is closely related to cumulative effect of buckling and bending deformation of the strut. By increasing the buckling deformation on the struts through cell shape design, the cyclic ratcheting rate of the meshes during cyclic deformation was decreased and accordingly, the compressive fatigue strength was increased. With increasing bending deformation of struts, fatigue crack growth in struts contributed more to the fatigue damage of meshes. Rough surface and pores contained in the struts significantly deteriorated the compressive fatigue strength of the struts. By optimizing the buckling and bending deformation through cell shape design, Ti-6Al 4V alloy cellular solids with high fatigue strength and low modulus can be fabricated by the EBM technique. PMID- 26878294 TI - Protective role of Th17 cells in pulmonary infection. AB - Th17 cells are characterized as preferential producer of interleukins including IL-17A, IL-17F, IL-21 and IL-22. Corresponding receptors of these cytokines are expressed on number of cell types found in the mucosa, including epithelial cells and fibroblasts which constitute the prime targets of the Th17-associated cytokines. Binding of IL-17 family members to their corresponding receptors lead to modulation of antimicrobial functions of target cells including alveolar epithelial cells. Stimulated alveolar epithelial cells produce antimicrobial peptides and are involved in granulepoesis, neutrophil recruitment and tissue repair. Mucosal immunity mediated by Th17 cells is protective against numerous pulmonary pathogens including extracellular bacterial and fungal pathogens. This review focuses on the protective role of Th17 cells during pulmonary infection, highlighting subset differentiation, effector cytokines production, followed by study of the binding of these cytokines to their corresponding receptors, the subsequent signaling pathway they engender and their effector role in host defense. PMID- 26878296 TI - 'The Carter efficiency programme is a world first'. PMID- 26878295 TI - Development of a cost-effective vaccine candidate with outer membrane vesicles of a tolA-disrupted Shigella boydii strain. AB - Our previous studies on outer membrane vesicles based vaccine development against shigellosis, revealed the inability of Shigella to release significant amount of vesicles naturally, during growth. Disruption of tolA, one of the genes of the Tol-Pal system of Gram negative bacterial membrane, has increased the vesicle release rate of a Shigella boydii type 4 strain to approximately 60% higher. We also noticed the vesicles, released from tolA-disrupted strain captured more OmpA protein and lipopolysaccharide, compared to the vesicles released from its wild type prototype. Six to seven weeks old BALB/c mice, immunized with 25 MUg of three oral doses of the vesicles, released by tolA mutant, conferred 100% protection against lethal homologous challenge through nasal route, compared to only 60% protection after the same dose of wild type immunogen. Mice, immunized with the vesicles from tolA-mutant, manifested significant secretion of mucosal IgG and IgA. A sharp and significant response of pro-inflammatory cytokines (TNF alpha, IL-6, IFN-gamma) were also observed in the lung lavage of these groups of mice, within 6h post challenge; but at 24h, these inflammatory cytokines showed the sign of subsidence and the system was taken over by the release of anti inflammatory cytokines (IL-4 and IL-10). Studies with naive peritoneal macrophages, proved further, the potency of these vesicles to stimulate nitric oxide and TNF-alpha, IL-12p70, IL-6 and IL-10 productions in-vitro. The ability of these vesicles to trigger polarization of CD4(+) T cells toward Th1 adaptive immune response, had also been observed along with the presence of anti inflammatory cytokines in the system. Our study demonstrated, the vesicles from tolA-disrupted Shigella were able to suppress Shigella-mediated inflammation in the host and could balance between inflammation and anti-inflammation, promoting better survival and health of the infected mice. Outer membrane vesicles from tolA-mutant, could be a potential cost-effective vaccine candidate against shigellosis. PMID- 26878298 TI - Wound healing and hyper-hydration: a counterintuitive model. AB - Winter's seminal work in the 1960s relating to providing an optimal level of moisture to aid wound healing (granulation and re-epithelialisation) has been the single most effective advance in wound care over many decades. As such the development of advanced wound dressings that manage the fluidic wound environment have provided significant benefits in terms of healing to both patient and clinician. Although moist wound healing provides the guiding management principle, confusion may arise between what is deemed to be an adequate level of tissue hydration and the risk of developing maceration. In addition, the counter intuitive model 'hyper-hydration' of tissue appears to frustrate the moist wound healing approach and advocate a course of intervention whereby tissue is hydrated beyond what is a normally acceptable therapeutic level. This paper discusses tissue hydration, the cause and effect of maceration and distinguishes these from hyper-hydration of tissue. The rationale is to provide the clinician with a knowledge base that allows optimisation of treatment and outcomes and explains the reasoning behind wound healing using hyper-hydration. Declaration of interest: K. Cutting is a Clinical Research Consultant to the medical device and biotechnology industry. M. Rippon is Visiting Clinical Research Fellow, University of Huddersfield and K. Ousey provides consultancy for a range of companies through the University of Huddersfield including consultancy services for Paul Hartmann Ltd on HydroTherapy products. PMID- 26878297 TI - A novel approach to antibiofilm susceptibility testing using a thermo-reversible matrix. AB - OBJECTIVE: Biofilm microorganisms are known to have a much higher tolerance to antimicrobials compared to their planktonic equivalents. Therefore, traditional antimicrobial susceptibility testing may not extrapolate to clinical treatment of infections of biofilm origin, and as a result, there is a need to not only develop antimicrobials with antibiofilm activity, but also suitable in vitro testing methods for their evaluation. In this study, we report on a novel method of antibiofilm testing using a thermo-reversible matrix (poloxamer 407), coupled with live/dead staining of bacteria cultured from the matrix. METHOD: Pseudomonas aeruginosa (NCIMB 8626) was cultured in medium containing poloxamer 407 at 37 degrees C for 24 hours to generate biofilms. The preparation was cooled to liquefy the poloxamer and allow recovery of the biofilm cells, which were then stained with SYTO9 to determine viability following exposure to four antimicrobials: polyhexanide, octenadine dihydrochloride, povidone-iodine and silver carbonate. Over an 8-minute time period, fluorescence levels were spectrophotometrically measured and compared with bacterial controls, cultured in the absence of poloxamer and without antimicrobial. RESULTS: Untreated cells showed no reduction in viability over this period. Importantly, planktonic cells were more susceptible to test agents compared with those of a 'biofilm' phenotype cultured in poloxamer. Antibiofilm activity was evident for all of the test agents, with highest relative activity seen with octenadine dihydrochloride. CONCLUSION: In summary, a novel and relatively rapid approach to screen compounds for antibiofilm activity has been described. The method uses standard laboratory equipment and can be readily adapted to test a wide range of microorganisms and other antibiofilm compounds. DECLARATION OF INTEREST: This research was, in part, supported by Advanced Medical Solutions in the form of a Knowledge Transfer Project. Mr J. Nosworthy was employed by Advanced Medical Solutions. There are no other conflicts of interests to declare. PMID- 26878299 TI - Binding of two bacterial biofilms to dialkyl carbamoyl chloride (DACC)-coated dressings in vitro. AB - OBJECTIVE: To date only planktonic bacteria have been shown to bind irreversibly to dialkyl carbamoyl chloride (DACC)-coated Cutimed Sorbact dressings. Therefore, this study was designed to determine whether bacterial biofilm bound to the DACC coated dressing in vitro. METHOD: Samples of DACC-coated dressings and uncoated control dressings (supplied by BSN medical Ltd, Hull) were placed in contact with plastic coverslips on which biofilms of either Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA) had been cultivated for 24 hours. Dressing samples were examined by scanning electron microscopy to detect the presence of biofilm. RESULTS: Pseudomonas aeruginosa biofilm bound avidly to both DACC-coated and uncoated dressing samples. MRSA bound more extensively to DACC-coated dressings than to uncoated samples. CONCLUSION: Biofilms of two different test bacteria bound to dressings in vitro with the DACC-coating on the dressings enhancing the binding of MRSA biofilm. DECLARATION OF INTEREST: This study was supported by BSN medical Ltd (Hull). The company had no influence on the experimental design or the interpretation of the results. PMID- 26878300 TI - Letters--Response to call to action: the proposed National Formulary for Wound Care. PMID- 26878301 TI - Photoacoustic imaging of real-time oxygen changes in chronic leg ulcers after topical application of a haemoglobin spray: a pilot study. AB - OBJECTIVE: To use a non-invasive measurement of oxygen saturation in chronic leg ulcers after the application of a topical haemoglobin spray to investigate if photoacoustic tomography is able to measure the oxygen saturation and if the stimulated oxygen increase can be demonstrated. METHOD: We measured the oxygen saturation of the ulcer tissue in five patients with chronic leg ulcers before application and 5 and 20 minutes after application of the haemoglobin spray, using photoacoustic tomography as a new method to assess oxygenation in real time. RESULTS: The average oxygen saturation showed a significant increase from 56.4% before to 69% (p=0.042) after 5 minutes and 78.8% (p=0.043) 20 minutes after the topical haemoglobin application. CONCLUSION: The oxygenation status of chronic, hard-to-heal wounds is gaining increasing interest in modern wound therapy. Topical haemoglobin spray is a new and effective method to increase the oxygenation in the ulcer tissue, but until now the link between clinical results and the mode of action was unclear. We were able to show for the first time that the use of a topical haemoglobin spray leads to an increase in oxygen saturation in vivo using photoacoustic tomography. DECLARATION OF INTEREST: Joachim Dissemond received financial support from the company SastoMed for several scientific projects as well as for lectures and as an advisor. The haemoglobin spray was provided by SastoMed GmbH (Georgsmarienhutte, Germany). PMID- 26878302 TI - In vitro activity of an engineered honey, medical-grade honeys, and antimicrobial wound dressings against biofilm-producing clinical bacterial isolates. AB - OBJECTIVE: Honey is recognised to be a good topical wound care agent owing to a broad-spectrum of antimicrobial activity combined with healing properties. Surgihoney RO (SH1) is a product based on honey that is engineered to produce enhanced reactive oxygen species (ROS) and has been reported to be highly antimicrobial. The objective was to investigate the ability of the engineered honey and its comparators to prevent biofilm formation in vitro. METHOD: We tested the ability of three medical-grade honeys SH1, Activon manuka honey (MH) and Medihoney manuka honey (Med), alongside five antimicrobial dressings (AMDs) to prevent the formation of biofilms by 16 isolates. Honeys were serially double diluted from 1:3 down to 1:6144 and the lowest dilution achieving a statistically significant reduction in biomass of at least 50%, compared with untreated controls, was recorded. RESULTS: Although all the honeys were antibacterial and were able to prevent the formation of biofilms, SH1 was the most potent, with efficacy at lower dilutions than the medical honeys for five isolates, and equivalent dilutions for a further six. Additionally, SH1 was superior in antibacterial potency to three commercially available AMDs that contain honey. CONCLUSION: SH1 is effective at preventing bioflms from forming and is superior to medical honeys and AMDs in in vitro tests. DECLARATION OF INTEREST: Surgihoney RO was provided free of charge for testing by Matoke Holdings, UK and the hospital pharmacy provided the other honeys and dressings. This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. PMID- 26878303 TI - Late costal osteomyelitis with a cutaneous fistula after flame burns: a case report. AB - Chest wall defects are an unusual complication of burn injury, generally seen after high-voltage electrical burns. Here we report the case of a 57-year-old man who developed costal chondritis and osteomyelitis 23 months after flame injury, which covered 50% of the total body surface area. Management included the resection of two ribs and coverage with an omental flap, overlaid by a split thickness skin graft during the same surgical procedure. Declaration of interest: The authors have no conflict of interest to declare. PMID- 26878304 TI - Motives for marijuana use among heavy-using high school students: An analysis of structure and utility of the Comprehensive Marijuana Motives Questionnaire. AB - Motives for marijuana use are important predictors of problematic outcomes associated with marijuana use. Most measures, to date, were developed by adapting alcohol motives measures. However, the Comprehensive Marijuana Motives Questionnaire (CMMQ) was created using a bottom-up approach to evaluate twelve distinct motives for use. The CMMQ was developed and validated in a normative college population. As such, no known study has evaluated the factor structure and utility of the CMMQ in a heavy-using, high school student population. The current study utilized a sample of 252 heavy marijuana-using high school students recruited for a combination motivational enhancement/cognitive behavioral intervention. Results from baseline measures indicated that the factor structure of the CMMQ was maintained in this population. Results from multiple regression analyses revealed distinct relationships with measures of negative consequences of use, including indices of marijuana use, marijuana-related problems, self efficacy, and internalizing and externalizing symptoms. In particular, the Coping motive was associated with several negative outcomes, which is consistent with previous marijuana and alcohol motives literature. Results suggest that the CMMQ may be useful in assessing marijuana motives among heavy marijuana-using adolescents. PMID- 26878305 TI - Charge Type, Charge Spacing, and Hydrophobicity of Arginine-Rich Cell-Penetrating Peptides Dictate Gene Transfection. AB - Noncovalent complexation of plasmid DNA (pDNA) with cell-penetrating peptides (CPPs) forms relatively large complexes with poor gene expression. Yet, condensing these CPP-pDNA complexes via addition of calcium chloride produces small and stable nanoparticles with high levels of gene expression. This simple formulation offered high transfection efficiency and negligible cytotoxicity in HEK-293 (a virus-immortalized kidney cell) and A549 (a human lung cancer cell line). Small changes in CPP charge type, charge spacing, and hydrophobicity were studied by using five arginine-rich CPPs: the well-known hydrophilic polyarginine R9 peptide, a hydrophilic RH9 peptide, and three amphiphilic peptides (RA9, RL9, and RW9) with charge distributions that favor membrane penetration. R9 and RW9 nanoparticles were significantly more effective than the other CPPs under most formulation conditions. However, these CPPs exhibit large differences in membrane penetration potential. Maximum transfection resulted from an appropriate balance of complexing with pDNA, releasing DNA, and membrane penetration potential. PMID- 26878306 TI - A New Beginning. PMID- 26878307 TI - Comments on "Evaluation Indexes of Military Hospitals From the Experts' Perspective: A Qualitative Study"-ERRATUM. PMID- 26878309 TI - Utilization of Health Care Coalitions and Resiliency Forums in the United States and United Kingdom: Different Approaches to Strengthen Emergency Preparedness. AB - The process for developing national emergency management strategies for both the United States and the United Kingdom has led to the formulation of differing approaches to meet similar desired outcomes. Historically, the pathways for each are the result of the enactment of legislation in response to a significant event or a series of events. The resulting laws attempt to revise practices and policies leading to more effective and efficient management in preparing, responding, and mitigating all types of natural, manmade, and technological hazards. Following the turn of the 21st century, each country has experienced significant advancements in emergency management including the formation and utilization of 2 distinct models: health care coalitions in the United States and resiliency forums in the United Kingdom. Both models have evolved from circumstances and governance unique to each country. Further in-depth study of both approaches will identify strengths, weaknesses, and existing gaps to meet continued and future challenges of our respective disaster health care systems. PMID- 26878308 TI - Value-Based Emergency Management. AB - This article touches on the complex and decentralized network that is the US health care system and how important it is to include emergency management in this network. By aligning the overarching incentives of opposing health care organizations, emergency management can become resilient to up-and-coming changes in reimbursement, staffing, and network ownership. Coalitions must grasp the opportunity created by changes in value-based purchasing and impending Centers for Medicare and Medicaid Services emergency management rules to engage payers, physicians, and executives. Hope and faith in doing good is no longer enough for preparedness and health care coalitions; understanding how physicians are employed and health care is delivered and paid for is now necessary. Incentivizing preparedness through value-based compensation systems will become the new standard for emergency management. PMID- 26878310 TI - Abatacept for the treatment of systemic lupus erythematosus. AB - INTRODUCTION: Due to improvements in our understanding of the pathogenesis of systemic lupus erythematosus (SLE), several target drugs have been and are being developed. One of the possible targets in SLE is co-stimulation between antigen presenting cells and T cells. Abatacept is a co-stimulation moderator approved for the treatment of several autoimmune diseases. There is an unmet need for drugs with a better efficacy and safety profile when treating patients with SLE. AREAS COVERED: In this review, the authors discuss the mechanism of action of abatacept including its role in the immune system and glomeruli, and relevant information about its clinical efficacy and safety. Possible explanations for the failure of previous randomized clinical trials are also discussed. EXPERT OPINION: Abatacept has demonstrated efficacy in other autoimmune diseases, but in SLE, randomized clinical trials have failed to achieve their primary outcome. Despite these disappointing results and based on its mechanism of action, abatacept seems to have a role in lupus nephritis and arthritis. This should be corroborated with new trials which hopefully will overcome the design pitfalls of the ones conducted to date. PMID- 26878313 TI - Orbital symmetry of charge-density-wave order in La1.875Ba0.125CuO4 and YBa2Cu3O6.67. AB - Recent theories of charge-density-wave (CDW) order in high-temperature superconductors have predicted a primarily d CDW orbital symmetry. Here, we report on the orbital symmetry of CDW order in the canonical cuprate superconductors La1.875Ba0.125CuO4 (LBCO) and YBa2Cu3O6.67 (YBCO), using resonant soft X-ray scattering and a model mapped to the CDW orbital symmetry. From measurements sensitive to the O sublattice, we conclude that LBCO has predominantly s' CDW orbital symmetry, in contrast to the d orbital symmetry recently reported in other cuprates. Furthermore, we show for YBCO that the CDW orbital symmetry differs along the a and b crystal axes and that these both differ from LBCO. This work highlights CDW orbital symmetry as an additional key property that distinguishes the different cuprate families. We discuss how the CDW symmetry may be related to the '1/8-anomaly' and to static spin ordering. PMID- 26878311 TI - The doxastic shear pin: delusions as errors of learning and memory. AB - We reconsider delusions in terms of a "doxastic shear pin", a mechanism that errs so as to prevent the destruction of the machine (brain) and permit continued function (in an attenuated capacity). Delusions may disable flexible (but energetically expensive) inference. With each recall, delusions may be reinforced further and rendered resistant to contradiction. We aim to respond to deficit accounts of delusions - that delusions are only a problem without any benefit - by considering delusion formation and maintenance in terms of predictive coding. We posit that brains conform to a simple computational principle: to minimize prediction error (the mismatch between prior top-down expectation and current bottom-up input) across hierarchies of brain regions and psychological representation. Recent data suggest that delusions may form in the absence of constraining top-down expectations. Then, once formed, they become new priors that motivate other beliefs, perceptions, and actions by providing strong (sometimes overriding) top-down expectation. We argue that delusions form when the shear-pin breaks, permitting continued engagement with an overwhelming world, and ongoing function in the face of paralyzing difficulty. This crucial role should not be ignored when we treat delusions: we need to consider how a person will function in the world without them.. PMID- 26878312 TI - Highly mobile ferroelastic domain walls in compositionally graded ferroelectric thin films. AB - Domains and domain walls are critical in determining the response of ferroelectrics, and the ability to controllably create, annihilate, or move domains is essential to enable a range of next-generation devices. Whereas electric-field control has been demonstrated for ferroelectric 180 degrees domain walls, similar control of ferroelastic domains has not been achieved. Here, using controlled composition and strain gradients, we demonstrate deterministic control of ferroelastic domains that are rendered highly mobile in a controlled and reversible manner. Through a combination of thin-film growth, transmission-electron-microscopy-based nanobeam diffraction and nanoscale band excitation switching spectroscopy, we show that strain gradients in compositionally graded PbZr1-xTixO3 heterostructures stabilize needle-like ferroelastic domains that terminate inside the film. These needle-like domains are highly labile in the out-of-plane direction under applied electric fields, producing a locally enhanced piezoresponse. This work demonstrates the efficacy of novel modes of epitaxy in providing new modalities of domain engineering and potential for as-yet-unrealized nanoscale functional devices. PMID- 26878314 TI - Magnetization switching by spin-orbit torque in an antiferromagnet-ferromagnet bilayer system. AB - Spin-orbit torque (SOT)-induced magnetization switching shows promise for realizing ultrafast and reliable spintronics devices. Bipolar switching of the perpendicular magnetization by the SOT is achieved under an in-plane magnetic field collinear with an applied current. Typical structures studied so far comprise a nonmagnet/ferromagnet (NM/FM) bilayer, where the spin Hall effect in the NM is responsible for the switching. Here we show that an antiferromagnet/ferromagnet (AFM/FM) bilayer system also exhibits a SOT large enough to switch the magnetization of the FM. In this material system, thanks to the exchange bias of the AFM, we observe the switching in the absence of an applied field by using an antiferromagnetic PtMn and ferromagnetic Co/Ni multilayer with a perpendicular easy axis. Furthermore, tailoring the stack achieves a memristor-like behaviour where a portion of the reversed magnetization can be controlled in an analogue manner. The AFM/FM system is thus a promising building block for SOT devices as well as providing an attractive pathway towards neuromorphic computing. PMID- 26878315 TI - Structured light enables biomimetic swimming and versatile locomotion of photoresponsive soft microrobots. AB - Microorganisms move in challenging environments by periodic changes in body shape. In contrast, current artificial microrobots cannot actively deform, exhibiting at best passive bending under external fields. Here, by taking advantage of the wireless, scalable and spatiotemporally selective capabilities that light allows, we show that soft microrobots consisting of photoactive liquid crystal elastomers can be driven by structured monochromatic light to perform sophisticated biomimetic motions. We realize continuum yet selectively addressable artificial microswimmers that generate travelling-wave motions to self-propel without external forces or torques, as well as microrobots capable of versatile locomotion behaviours on demand. Both theoretical predictions and experimental results confirm that multiple gaits, mimicking either symplectic or antiplectic metachrony of ciliate protozoa, can be achieved with single microswimmers. The principle of using structured light can be extended to other applications that require microscale actuation with sophisticated spatiotemporal coordination for advanced microrobotic technologies. PMID- 26878316 TI - Cardiac electrophysiology procedures guided by novel non-fluoroscopic catheter tracking systems. PMID- 26878317 TI - A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or beta-cell mass in NZO mice. AB - BACKGROUND/OBJECTIVES: Dietary guidelines for the past 20 years have recommended that dietary fat should be minimized. In contrast, recent studies have suggested that there could be some potential benefits for reducing carbohydrate intake in favor of increased fat. It has also been suggested that low-carbohydrate diets be recommended for people with type 2 diabetes. However, whether such diets can improve glycemic control will likely depend on their ability to improve beta-cell function, which has not been studied. The objective of the study was to assess whether a low-carbohydrate and therefore high-fat diet (LCHFD) is beneficial for improving the endogenous insulin secretory response to glucose in prediabetic New Zealand Obese (NZO) mice. METHODS: NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic beta-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. beta-Cell mass was assessed in histological sections of pancreata collected at the end of the study. RESULTS: In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was beta-cell mass (P=0.75). CONCLUSIONS: An LCHFD is unlikely to be of benefit for preventing the decline in beta-cell function associated with the progression of hyperglycemia in type 2 diabetes. PMID- 26878318 TI - The effects of potatoes and other carbohydrate side dishes consumed with meat on food intake, glycemia and satiety response in children. AB - BACKGROUND: The effect of carbohydrate (CHO) foods on blood glucose (BG) is ranked by their glycemic index (GI). Boiled and mashed potatoes (BMPs) are ranked as high GI foods, whereas pasta and rice have moderate GI rankings. The objective of this study was to compare ad libitum consumption of common CHO dishes consumed with meat on meal-time food intake and post-meal satiety, BG, insulin and gut hormones in 11- to 13-year-old normal weight children. METHODS: Two randomized crossover studies were conducted. At weekly intervals, children (experiment 1: 12 males (M), 8 females (F); experiment 2: 6M, 6 F) received in random order 1 of 5 CHO side dishes of rice, pasta, BMP, fried French fries (FFF) or baked French fries (BFF) eaten freely together with a fixed amount of lean beef (100 g). In experiment-1, food intake over 30 min and subjective appetite were measured for 120 min. In experiment-2, the same outcomes were measured along with BG, plasma insulin and gut hormones. RESULTS: The results for boys and girls were pooled as sex was not a factor. In both experiments, children consumed 30-40% less calories at meals with BMP (P<0.0001) compared with all other treatments, which were similar. BMP increased satiety, expressed as a change in appetite per kilocalorie, more than all other treatments (P<0.0001). FFF resulted in the lowest (P<0.0001) glucose and insulin at meal end and post-meal and peptide YY (PYY) post-meal. Blood measures were similar among all other treatments. CONCLUSIONS: The physiological functions of CHO foods consumed ad libitum at meal time on food intake, appetite, BG, insulin and gut hormone responses in children is not predicted by the GI. PMID- 26878323 TI - Facile fabrication of aloe vera containing PCL nanofibers for barrier membrane application. AB - Guided tissue regeneration (GTR) is a widely used method in dental surgical procedures that utilizes a barrier membrane to exclude migration of epithelium and ensure repopulation of periodontal ligament cells at the sites having insufficient gingiva. Commercial GTR membranes are typically composed of synthetic polymers that have had mild clinical success mostly because of their lack of proper bioactivity and appropriate degradation profile. In this study, a natural polymer, aloe vera was blended with polycaprolactone (PCL) to create nanofibrous GTR membranes by electrospinning. Aloe vera has proven anti inflammatory properties and enhances the regeneration of periodontium tissues. PCL, a synthetic polymer, is well known to produce miscible polyblends nanofibers with natural polymers. Nanofibrous membranes with varying composition of PCL to aloe vera were fabricated, and several physicochemical and biological properties, such as fiber morphology, wettability, chemical structure, mechanical strength, and cellular compatibility of the membranes were analyzed. PCL/aloe vera membranes with ratios from 100/00 to 70/30 showed good uniformity in fiber morphology and suitable mechanical properties, and retained the integrity of their fibrous structure in aqueous solutions. Experimental results, using cell viability assay and cell attachment observation, showed that the nanofibrous membranes support 3T3 cell viability and could be a potential candidate for GTR therapy. PMID- 26878320 TI - Raised Ca125 and ascites: Is this ovarian cancer till proven otherwise? PMID- 26878319 TI - A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. AB - A challenge for tissue engineering is producing three-dimensional (3D), vascularized cellular constructs of clinically relevant size, shape and structural integrity. We present an integrated tissue-organ printer (ITOP) that can fabricate stable, human-scale tissue constructs of any shape. Mechanical stability is achieved by printing cell-laden hydrogels together with biodegradable polymers in integrated patterns and anchored on sacrificial hydrogels. The correct shape of the tissue construct is achieved by representing clinical imaging data as a computer model of the anatomical defect and translating the model into a program that controls the motions of the printer nozzles, which dispense cells to discrete locations. The incorporation of microchannels into the tissue constructs facilitates diffusion of nutrients to printed cells, thereby overcoming the diffusion limit of 100-200 MUm for cell survival in engineered tissues. We demonstrate capabilities of the ITOP by fabricating mandible and calvarial bone, cartilage and skeletal muscle. Future development of the ITOP is being directed to the production of tissues for human applications and to the building of more complex tissues and solid organs. PMID- 26878324 TI - An analysis of planned versus delivered airway doses during stereotactic lung radiotherapy for central tumors. PMID- 26878325 TI - Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: In vitro evaluation, pharmacokinetic and biodistribution in rats. AB - The purpose of this study was to develop folic acid functionalized long circulating co-encapsulated docetaxel (DTX) and curcumin (CRM) solid lipid nanoparticles (F-DC-SLN) to improve the pharmacokinetic and efficacy of DTX therapy. F-DC-SLN was prepared by hot melt-emulsification method and optimized by face centered-central composite design (FC-CCD). The SLN was characterized in terms of size and size distribution, drug entrapment efficiency and release profile. The cytotoxicity and cell uptake of the SLN formulations were evaluated in MCF-7 and MDA-MB-231 cell lines. The in vivo pharmacokinetic and biodistribution were studied in Wistar rats. F-DC-SLN exhibited 247.5 +/- 3.40 nm particle size with 73.88 +/- 1.08% entrapment efficiency and zeta potential of 14.53 +/- 3.6 mV. Transmission electron microscopy (TEM) revealed spherical morphology of the SLN. Fluorescence microscopy confirmed the targeting efficacy of F-DC-SLN in MCF-7 cells. F-DC-SLN exhibited a significant increase in area under the curve (594.21 +/- 64.34 versus 39.05 +/- 7.41 MUg/mL h) and mean residence time (31.14 +/- 19.94 versus 7.24 +/- 4.51 h) in comparison to Taxotere(r). In addition, decreased DTX accumulation from F-DC-SLN in the heart and kidney in comparison to Taxotere may avoid to toxicity these vital organs. In conclusion, the F-DC-SLN improved the efficacy and pharmacokinetic profile of DTX exhibiting enhanced potential in optimizing breast cancer therapy. PMID- 26878326 TI - Transoral Incisionless Fundoplication for Refractory Gastroesophageal Reflux Disease: Where Do We Stand? AB - Gastroesophageal reflux disease (GERD) is a chronic, progressive, and costly medical condition affecting a substantial proportion of the world population, predominantly the Western population. The available treatment options for patients with refractory GERD symptoms are limited to either laparoscopic surgery with significant sequelae or potentially lifelong, high-dose proton pump inhibitor therapy. The restoration of the antireflux competence of the gastroesophageal junction at the anatomic and physiologic levels is critical for the effective long-term treatment of GERD. Transoral incisionless fundoplication (TIF) surgery is a safe, well-tolerated, and effective treatment that has yielded significant symptomatic improvement in patients with medically refractory GERD symptoms. In this review article, we have summarized case series and reports describing the role of TIF for patients with gastroesophageal reflux symptoms. The reported indications, techniques, complications, and success rates are also discussed. PMID- 26878328 TI - Low-Lying pi* Resonances of Standard and Rare DNA and RNA Bases Studied by the Projected CAP/SAC-CI Method. AB - Low-lying pi* resonance states of DNA and RNA bases have been investigated by the recently developed projected complex absorbing potential (CAP)/symmetry-adapted cluster-configuration interaction (SAC-CI) method using a smooth Voronoi potential as CAP. In spite of the challenging CAP applications to higher resonance states of molecules of this size, the present calculations reproduce resonance positions observed by electron transmission spectra (ETS) provided the anticipated deviations due to vibronic effects and limited basis sets are taken into account. Moreover, for the standard nucleobases, the calculated positions and widths qualitatively agree with those obtained in previous electron scattering calculations. For guanine, both keto and enol forms were examined, and the calculated values of the keto form agree clearly better with the experimental findings. In addition to these standard bases, three modified forms of cytosine, which serve as epigenetic or biomarkers, were investigated: formylcytosine, methylcytosine, and chlorocytosine. Last, a strong correlation between the computed positions and the observed ETS values is demonstrated, clearly suggesting that the present computational protocol should be useful for predicting the pi* resonances of congeners of DNA and RNA bases. PMID- 26878327 TI - Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. AB - BACKGROUND: Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016. OBJECTIVES: We aimed to perform a systematic review and meta-analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events. SEARCH METHODS: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest. DATA COLLECTION AND ANALYSIS: We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia - five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia). AUTHORS' CONCLUSIONS: Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34 degrees C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in-hospital cardiac arrest, asystole or non-cardiac causes of arrest. PMID- 26878329 TI - Participant evaluation of simulation training using crew resource management in a hospital setting in Hong Kong. AB - INTRODUCTION: A simulation team-based crew resource management training programme was developed to provide a unique multidisciplinary learning experience for health care professionals in a regional hospital in Hong Kong. In this study, we evaluated how health care professionals perceive the programme. METHODS: A cross sectional questionnaire survey was conducted in the Multidisciplinary Simulation and Skills Centre at Queen Elizabeth Hospital in Hong Kong. A total of 55 individuals in the departments of Obstetrics and Gynaecology, Anaesthesiology and Operating Theatre Services, Intensive Care Unit, and Accident and Emergency participated in the study between June 2013 and December 2013. The course content was specially designed according to the needs of the clinical departments and comprised a lecture followed by scenarios and debriefing sessions. Principles of crew resource management were introduced and taught throughout the course by trained instructors. Upon completion of each course, the participants were surveyed using a 5-point Likert scale and open-ended questions. RESULTS: The participant's responses to the survey were related to course organisation and satisfaction, realism, debriefing, and relevance to practice. The overall rating of the training programme was high, with mean Likert scale scores of 4.1 to 4.3. The key learning points were identified as closed-loop communication skills, assertiveness, decision making, and situational awareness. CONCLUSIONS: The use of a crew resource management simulation-based training programme is a valuable teaching tool for frontline health care staff. Concepts of crew resource management were relevant to clinical practice. It is a highly rated training programme and our results support its broader application in Hong Kong. PMID- 26878330 TI - Suspected levamisole intoxication in calves. AB - CASE HISTORY: A group of 32 Friesian and four Hereford calves, 3-4 months old with body weights between 100-120 kg, were purchased from a weaner sale. On arrival at the property the Hereford calves were treated with a combination anthelmintic containing 2 g/L abamectin and 80 g/L levamisole hydrochloride. Shortly afterwards they developed tremors and frothing from the mouth, and two died overnight. The Friesian calves were treated with the same anthelmintic on the following day, when some showed hypersalivation and frothing from the mouth. CLINICAL FINDINGS: Examination of the three most severely affected Friesian calves revealed severe nicotinic-type symptoms including hypersalivation, frothing from the mouth, muscle tremors, recumbency, rapid respiration, hyperaesthesia, and central nervous system depression. Other calves showed mild to moderate signs of intoxication including restlessness, tail switching, salivation, tremors, frequent defaecation, mild colic and jaw chomping. Two calves died shortly afterwards. An adverse drug event investigation revealed that the formulation and quality of the anthelmintic was within the correct specification, and that the drench gun was functioning correctly. DIAGNOSIS: Suspected levamisole intoxication due to a combination of possible overdosing, dehydration, and stress caused by transportation and prolonged yarding. CLINICAL RELEVANCE: Susceptibility to levamisole toxicity in New Zealand calves can be increased if factors like dehydration or stress are present. Levamisole has a narrow margin of safety, and overdosing in calves can easily occur if the dose rate is not based on their actual weight or health status. PMID- 26878331 TI - Combination of photothermal and photodynamic inactivation of cancer cells through surface plasmon resonance of a gold nanoring. AB - We demonstrate effective inactivation of oral cancer cells SAS through a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) effects based on localized surface plasmon resonance (LSPR) around 1064 nm in wavelength of a Au nanoring (NRI) under femtosecond (fs) laser illumination. The PTT effect is caused by the LSPR-enhanced absorption of the Au NRI. The PDT effect is generated by linking the Au NRI with the photosensitizer of sulfonated aluminum phthalocyanines (AlPcS) for producing singlet oxygen through the LSPR-enhanced two-photon absorption (TPA) excitation of AlPcS. The laser threshold intensity for cancer cell inactivation with the applied Au NRI linked with AlPcS is significantly lower when compared to that with the Au NRI not linked with AlPcS. The comparison of inactivation threshold intensity between the cases of fs and continuous laser illuminations at the same wavelength and with the same average power confirms the crucial factor of TPA under fs laser illumination for producing the PDT effect. PMID- 26878332 TI - Cross-cultural adaptation, reliability, and validity of the Japanese version of the Cumberland ankle instability tool. AB - Purpose To study validity and reliability of a Japanese version of the Cumberland Ankle Instability Tool and to determine the optimal cutoff score. Methods In this study, the questionnaire was cross-culturally adapted into Japanese. The psychometric properties tested in the Japanese version of the CAIT were measured for criteria validity, internal consistency and test-retest reliability in 111 collegiate soccer athletes. We also established the questionnaire cutoff score for discriminating between individuals with and without CAI. Results There was a significant correlation between the Japanese version of the CAIT and the Karlsson score (r = 0.604, p < 0.001). The questionnaire had a high internal consistency (Cronbach's alpha = 0.833) and reliability [intraclass correlation coefficient (ICC) = 0.826, 95% confidence interval (CI): 0.732-0.888]. The optimal cutoff score was <=25, which was consistent with previous reports. Conclusions The Japanese version of the CAIT has been shown to be a valid and reliable questionnaire for determining the presence of CAI. We expect that researchers and clinicians will use the Japanese version of the CAIT in Japan. Implications for Rehabilitation Chronic Ankle Instability (CAI), which not only increases recurrence rate of ankle sprain but also decreases athletic performance, is a residual symptom after ankle sprain. Cumberland Ankle Instability Tool, which has the reliability and validity to assess CAI, will be critically useful in assessment procedure for CAI. It is preferable for clinicians and researchers to use the native language version of the CAIT. PMID- 26878333 TI - Locally measuring the adhesion of InP directly bonded on sub-100 nm patterned Si. AB - A nano-scale analogue to the double cantilever experiment that combines instrumented nano-indentation and atomic force microscopy is used to precisely and locally measure the adhesion of InP bonded on sub-100 nm patterned Si using oxide-free or oxide-mediated bonding. Surface-bonding energies of 0.548 and 0.628 J m(-2), respectively, are reported. These energies correspond in turn to 51% and 57% of the surface bonding energy measured in unpatterned regions on the same samples, i.e. the proportion of unetched Si surface in the patterned areas. The results show that bonding on patterned surfaces can be as robust as on unpatterned surfaces, provided care is taken with the post-patterning surface preparation process and, therefore, open the path towards innovative designs that include patterns embedded in the Si guiding layer of hybrid III-V/Si photonic integrated circuits. PMID- 26878334 TI - Detection of an embolized central venous catheter fragment with endobronchial ultrasound. AB - An 84-year-old woman underwent Convex-probe Endobronchial Ultrasound (CP-EBUS) for 18 F-fluorodeoxyglucose avid subcarinal lymphadenopathy on Positron Emission Tomogram (PET) scan. Endobronchial ultrasound-guided transbronchial needle aspiration of the subcarinal lymph node revealed squamous cell lung carcinoma. A small hyperechoic rounded density was noted inside the lumen of the azygous vein. Based on chest computed tomography findings and her clinical history, this was felt to be a broken fragment of a peripherally inserted central catheter, which was placed for intravenous antibiotics, a few months prior to this presentation. To the best of our knowledge, this is the first ever CP-EBUS description of a broken fragment of central venous catheter. PMID- 26878336 TI - Amnioserosa development and function in Drosophila embryogenesis: Critical mechanical roles for an extraembryonic tissue. AB - Despite being a short-lived, extraembryonic tissue, the amnioserosa plays critical roles in the major morphogenetic events of Drosophila embryogenesis. These roles involve both cellular mechanics and biochemical signaling. Its best known role is in dorsal closure-well studied by both developmental biologists and biophysicists-but the amnioserosa is also important during earlier developmental stages. Here, we provide an overview of amnioserosa specification and its role in several key developmental stages: germ band extension, germ band retraction, and dorsal closure. We also compare embryonic development in Drosophila and its relative Megaselia to highlight how the amnioserosa and its roles have evolved. Placed in context, the amnioserosa provides a fascinating example of how signaling, mechanics, and morphogen patterns govern cell-type specification and subsequent morphogenetic changes in cell shape, orientation, and movement. Developmental Dynamics 245:558-568, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26878335 TI - Controlling Listeria monocytogenes and Leuconostoc mesenteroides in Uncured Deli style Turkey Breast Using a Clean Label Antimicrobial. AB - Interest in natural/organic meat products has resulted in the need to validate the effectiveness of clean label antimicrobials to increase safety and shelf life of these products. A Response Surface Methodology (RSM) was used to investigate the effects of varying levels of moisture, pH, and a commercial "clean-label" antimicrobial (cultured sugar-vinegar blend; CSVB) on the growth rate of Listeria monocytogenes and Leuconostoc mesenteroides in uncured turkey stored at 4 degrees C for 16 wk. Twenty treatment combinations of moisture (60% to 80%), pH (5.8 to 6.4), and CSVB (2.5% to 5.0%) were evaluated during phase I to develop growth curves for both microbe types, whereas the interactive effects of pH (5.8 to 6.4) and CSVB (0.0 to 4.75) were tested in 16 treatment combinations during Phase II at a single moisture level using L. monocytogenes only. CSVB inhibited L. monocytogenes growth in 14 of the 20 treatments tested in Phase I and in 12 of the 16 treatments in Phase II through 16 and 8 wk, respectively. In contrast, CSVB had little effect on L. mesenteroides, with growth inhibited in only 4 of 20 treatments in Phase I and was therefore not tested further in Phase II. Significant interactions of the RSM design coefficients yielded a predictive model for L. mesenteroides growth rate, but due to lack of growth, no growth rate model was developed for L. monocytogenes. CSVB was found to be an effective antilisteral antimicrobial, while having little effect on a spoilage microorganism. PMID- 26878337 TI - Thioether-Based Fluorescent Covalent Organic Framework for Selective Detection and Facile Removal of Mercury(II). AB - Heavy metal ions are highly toxic and widely spread as environmental pollutants. New strategies are being developed to simultaneously detect and remove these toxic ions. Herein, we take the intrinsic advantage of covalent organic frameworks (COFs) and develop fluorescent COFs for sensing applications. As a proof-of-concept, a thioether-functionalized COF material, COF-LZU8, was "bottom up" integrated with multifunctionality for the selective detection and facile removal of mercury(II): the pi-conjugated framework as the signal transducer, the evenly and densely distributed thioether groups as the Hg(2+) receptor, the regular pores facilitating the real-time detection and mass transfer, together with the robust COF structure for recycle use. The excellent sensing performance of COF-LZU8 was achieved in terms of high sensitivity, excellent selectivity, easy visibility, and real-time response. Meanwhile, the efficient removal of Hg(2+) from water and the recycling of COF-LZU8 offers the possibility for practical applications. In addition, X-ray photoelectron spectroscopy and solid state NMR investigations verified the strong and selective interaction between Hg(2+) and the thioether groups of COF-LZU8. This research not only demonstrates the utilization of fluorescent COFs for both sensing and removal of metal ions but also highlights the facile construction of functionalized COFs for environmental applications. PMID- 26878339 TI - Laparoscopic Ureterolithotomy in Children: With and Without Stent - Initial Tertiary Care Center Experience with More Than 1-Year Follow-Up. AB - Background The purpose of our study was to assess the safety and feasibility of transperitoneal laparoscopic ureterolithotomy (LU) in children with ureteric stones with and without a stent. Method Impacted ureteric stone of size >= 1.5 cm or ureteric stones that were refractory to shock wave lithotripsy (SWL)/ureteroscopy (URS) were considered for LU. From December 2009 to April 2012, 50 cases of LU were performed with a stent being placed. From May 2012 onward we now perform stentless LU and till now we have done approximately 64 such type of cases. Out of these, 48 have completed more than 1 year of follow-up and we took these as our study group and the previous 50 (LU with stent) as our control group. Baseline characteristics along with certain per- and postoperative findings of the two groups were noted and analyzed. Ultrasonography and X-ray kidney, ureter, and bladder region were done at 3, 9 months, 1 year, and yearly thereafter. Intravenous urography was done at 6 months statistical analysis was performed by using SPSS ver. 21 (SPSS Inc., Chicago, Illinois, United States). The data were analyzed by using the Mann-Whitney test and a p value of < 0.05 was considered significant. Results The baseline characteristics were similar in both the groups with 100% stone clearance in all. LU with stent differed from the stentless group in terms of more requirement of analgesics and the need for a second procedure for stent removal, but with no cases of urine leak in the postoperative period. Conclusion LU in children is a safe and viable option, especially for impacted stones or as a salvage procedure for ureteric stones when SWL or transureteral lithotripsy has failed. PMID- 26878338 TI - Innate immunity in vertebrates: an overview. AB - Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. PMID- 26878341 TI - Simulations of Ice Nucleation by Model AgI Disks and Plates. AB - Silver iodide is one of the most effective ice nuclei known. We use molecular dynamics simulations to investigate ice nucleation by AgI disks and plates with radii ranging from 1.15 to 2.99 nm. It is shown that disks and plates in this size range are effective ice nuclei, nucleating bulk ice at temperatures as warm as 14 K below the equilibrium freezing temperature, on simulation time scales (up to a few hundred nanoseconds). Ice nucleated on the Ag exposed surface of AgI disks and plates. Shortly after supercooling an ice cluster forms on the AgI surface. The AgI-stabilized ice cluster fluctuates in size as time progresses, but, once formed, it is constantly present. Eventually, depending on the disk or plate size and the degree of supercooling, a cluster fluctuation achieves critical size, and ice nucleates and rapidly grows to fill the simulation cell. Larger AgI disks and plates support larger ice clusters and hence can nucleate ice at warmer temperatures. This work may be useful for understanding the mechanism of ice nucleation on nanoparticles and active sites of larger atmospheric particles. PMID- 26878340 TI - Inhibition of protease-activated receptor 4 impairs platelet procoagulant activity during thrombus formation in human blood. AB - Essentials The platelet thrombin receptor, PAR4, is an emerging anti-thrombotic drug target. We examined the anti-platelet & anti-thrombotic effects of PAR4 inhibition in human blood. PAR4 inhibition impaired platelet procoagulant activity in isolated cells and during thrombosis. Our study shows PAR4 is required for platelet procoagulant function & thrombosis in human blood. SUMMARY: Background Thrombin-induced platelet activation is important for arterial thrombosis. Thrombin activates human platelets predominantly via protease activated receptor (PAR)1 and PAR4. PAR1 has higher affinity for thrombin, and the first PAR1 antagonist, vorapaxar, was recently approved for use as an antiplatelet agent. However, vorapaxar is contraindicated in a significant number of patients, owing to adverse bleeding events. Consequently, there is renewed interest in the role of platelet PAR4 in the setting of thrombus formation. Objectives To determine the specific antiplatelet effects of inhibiting PAR4 function during thrombus formation in human whole blood. Methods and Results We developed a rabbit polyclonal antibody against the thrombin cleavage site of PAR4, and showed it to be a highly specific inhibitor of PAR4-mediated platelet function. This function-blocking anti-PAR4 antibody was used to probe for PAR4 dependent platelet functions in human isolated platelets in the absence and presence of concomitant PAR1 inhibition. The anti-PAR4 antibody alone was sufficient to abolish the sustained elevation of cytosolic calcium level and consequent phosphatidylserine exposure induced by thrombin, but did not significantly inhibit integrin alphaII b beta3 activation, alpha-granule secretion, or aggregation. In accord with these in vitro experiments on isolated platelets, selective inhibition of PAR4, but not of PAR1, impaired thrombin activity (fluorescence resonance energy transfer-based thrombin sensor) and fibrin formation (anti-fibrin antibody) in an ex vivo whole blood flow thrombosis assay. Conclusions These findings demonstrate that PAR4 is required for platelet procoagulant function during thrombus formation in human blood, and suggest PAR4 inhibition as a potential target for the prevention of arterial thrombosis. PMID- 26878342 TI - The role of sand, marble chips and Typha latifolia in domestic wastewater treatment - a column study on constructed wetlands. AB - The relative importance of sand, marble chips and wetland plant Typha latifolia is evaluated in constructed wetlands (CWs) for the treatment of domestic wastewater intended for reuse in agriculture. The prototype CWs for the experiments are realized in polyvinyl chloride columns, which are grouped into four treatments, viz. sand (<2 mm) + Typha latifolia (cattail), sand, marble chips (5-20 mm) + cattail and marble chips. The removal percentage of organic and nutritional pollutants from the wastewater is measured at varying hydraulic retention time in the columns. The statistical analysis suggests that the main effects of sand and cattail are found to be significant (p < .05) for the removal of biological oxygen demand and chemical oxygen demand from the wastewater. The presence of cattail significantly (p < .01) contributes to the conversion of total nitrogen in wastewater into [Formula: see text] by fostering the growth of favorable microbes for the nitrification. The removal of [Formula: see text] and turbidity from the wastewater is significantly (p < .01) influenced by sand than the presence of cattail. The maximum [Formula: see text] adsorption capacity of the sand is estimated to be 2.5 mg/g. Marble chips have significantly (p < .01) influenced the removal of [Formula: see text]and its maximum removal capacity is estimated to be 9.3 mg/g. The negative correlation between the filter media biofilm and column hydraulic conductivity is also reported for all the treatments. Thus, the findings of this study elucidate the role of low-cost and easily available filter media and it will guide the environmental practitioners in designing cost-effective CWs for wastewater treatment. PMID- 26878344 TI - Our periodontal tissue: a masterpiece of evolution. PMID- 26878345 TI - Thermodynamic and kinetic studies of LiNi0.5Co0.2Mn0.3O2 as a positive electrode material for Li-ion batteries using first principles. AB - Ni-rich Li-based layered Ni, Co, and Mn (NCM) materials have shown tremendous promise in recent years as positive electrode materials for Li-ion batteries. This is evident as companies developing batteries for electrical vehicles are currently commercializing these materials. Despite the considerable research performed on LiNialphaCobetaMngammaO2 systems, we do not yet have a complete atomic level understanding of these materials. In this work we study the cationic ordering, thermodynamics, and diffusion kinetics of LiNi0.5Co0.2Mn0.3O2 (NCM 523). Initially, we show that cationic ordering can be predicted employing cheap atomistic simulations, instead of using expensive first-principles methods. Subsequently, we investigate the electrochemical, thermodynamic and kinetic properties of NCM-523 using density functional theory (DFT). Our results demonstrate the importance of including dispersion corrections to standard first principles functionals in order to correctly predict the lattice parameters of layered cathode materials. We also demonstrate that a careful choice of computational protocol is essential to reproduce the experimental intercalation potential trends observed in the LiNi0.5Co0.2Mn0.3O2 electrodes. Analysis of the electronic structure confirms an active role of Ni in the electrochemical redox process. Moreover, we confirm the experimental finding that on complete delithiation, this material remains in an O3 phase, unlike LiCoO2 and NCM-333. Finally, we study various pathways for the Li-ion diffusion in NCM-523, and pinpoint the preferred diffusion channel based on first principles simulations. Interestingly, we observe that the Li diffusion barrier in NCM-523 is lower than that in LiCoO2. PMID- 26878343 TI - Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods. AB - Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins responsible for the regulation of programmed cell death. Amplification of Mcl-1 is a common genetic aberration in human cancer whose overexpression contributes to the evasion of apoptosis and is one of the major resistance mechanisms for many chemotherapies. Mcl-1 mediates its effects primarily through interactions with pro-apoptotic BH3 containing proteins that achieve high affinity for the target by utilizing four hydrophobic pockets in its binding groove. Here we describe the discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design. These novel inhibitors exhibit low nanomolar binding affinities to Mcl-1 and >500-fold selectivity over Bcl-xL. X-ray structures of lead Mcl-1 inhibitors when complexed to Mcl-1 provided detailed information on how these small-molecules bind to the target and were used extensively to guide compound optimization. PMID- 26878346 TI - Early cytomegalovirus-specific T-cell response and estimated glomerular filtration rate identify patients at high risk of infection after renal transplantation. AB - BACKGROUND: Assessing the risk of cytomegalovirus (CMV) viremia in kidney transplant recipients (KTR) may be helpful to indicate in which patient it is worth starting antiviral treatment during preemptive strategy. METHODS: In 40 CMV seropositive KTR preemptively treated with ganciclovir, we used interferon (IFN) gamma ELISpot test to evaluate whether monitoring T cells directed against phosphoprotein (pp) 65 and immediate early (IE)-1 antigens could predict the onset of viremia. RESULTS: CMV viremia occurred in 24 patients (60%) within 120 days after transplantation. Non-viremic patients had higher anti-pp65, anti-IE-1 T cells, and estimated glomerular filtration rate (eGFR) in the first 90 days after transplantation. At logistic regression, anti-pp65, anti-IE-1 T cells, and eGFR measured at day 30 were significantly associated with CMV infection. Cutoff values of 15 spot-forming cells (SFCs)/200,000 peripheral blood mononuclear cells (PBMCs) for anti-IE, 40 SFCs/200,000 PBMCs for anti-pp65, and 46.6 mL/min/1.73 m(2) for eGFR, respectively, predicted the risk of CMV infection with high sensitivity and specificity (area under the receiver operating characteristic curve >0.75). Using a classification tree model, we identified as high-risk patients those showing anti-pp65 <42 SFCs/200,000 PBMCs and eGFR <62 mL/min/1.73 m(2) , as well as anti-pp65 >=42 and anti-IE-1 <6.5 SFCs/200,000 PBMCs. CONCLUSION: Monitoring CMV-specific T-cell responses and eGFR in the first month post transplant can identify patients at high risk of CMV infection, for whom preemptive antiviral therapy is recommended. PMID- 26878347 TI - Impact of offshore gas platforms on the structural and functional biodiversity of nematodes. AB - The Mediterranean Sea hosts hundreds of offshore gas platforms, whose activity represents a potential threat to marine ecosystems. Evidence from several studies indicates that nematodes can be highly sensitive to changes in the environmental quality. Here, we investigated the response of nematode assemblages to the presence of offshore gas platforms (located in the central Mediterranean Sea) in terms of spatial heterogeneity, structural and functional diversity. Since the effect of the investigated offshore platforms on macrofaunal assemblages were previously assessed by Terlizzi et al. (2008), the study provided also the opportunity to compare the response of different benthic compartments to the same impact related to fossil fuel extraction on marine environments. The platforms had a significant impact on nematode assemblages up to 1000 m distance from the structure. The effects were evident in term of: a) more homogeneous spatial distribution of nematode assemblages, b) increased trophic diversity of deposit feeders and c) changes in life strategies with an increase of opportunistic species in sediments closer to the platforms. Such effects seemed to be related to the dimension of the platform structures, rather than to chemical pollution or changes in food availability. These findings suggest that the platforms exert a physical alteration of the surrounding environment that is reflected by altered structural and functional traits of nematode biodiversity. The use of nematodes for monitoring the effects of the platforms only partially matched with the results obtained using macrofauna, providing further insights on potential outcomes on the functional response of marine assemblages to fossil fuel extraction. PMID- 26878348 TI - Pathogenic C9ORF72 Antisense Repeat RNA Forms a Double Helix with Tandem C:C Mismatches. AB - Expansion of a GGGGCC/CCCCGG repeat sequence in the first intron of the C9ORF72 gene is a leading cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). In this combined disorder, called c9FTD/ALS, the expansion is bidirectionally transcribed into sense and antisense repeat RNA associated with disease. To better understand the role of C9ORF72 repeat RNA in molecular disease pathology, we determined crystal structures of a [(CCCCGG)3(CCCC)] model antisense repeat RNA to 1.47 A resolution. The RNA structure was an A-form-like double helix composed of repeating and regularly spaced tandem C:C mismatch pairs that perturbed helical geometry and surface charge. Solution studies revealed a preference for A-form-like helical conformations as the repeat number increased. Results provide a structural starting point for rationalizing the contribution of repeat RNA to c9FTD/ALS molecular disease mechanisms and for developing molecules to target C9ORF72 repeat RNA as potential therapeutics. PMID- 26878351 TI - Ultrasound-responsive ultrathin multiblock copolyamide vesicles. AB - This study reports the self-assembly of novel polymer vesicles from an amphiphilic multiblock copolyamide, and the vesicles show a special structure with an ultrathin wall thickness of about 4.5 nm and a combined bilayer and monolayer packing model. Most interestingly, the vesicles are ultrasound responsive and can release the encapsulated model drugs in response to ultrasonic irradiation. PMID- 26878349 TI - Brain PET measurement of PDE10A occupancy by TAK-063, a new PDE10A inhibitor, using [11 C]T-773 in nonhuman primates. AB - Because phosphodiesterase 10A (PDE10A) degrades both cyclic adenosine monophosphate and cyclic guanosine monophosphate and is distributed mainly in the striatum, PDE10A inhibitors have been considered to potentially be useful therapeutic agents for psychiatric and neurodegenerative diseases such as schizophrenia and Huntington's disease. We measured striatal PDE10A occupancy by TAK-063, a newly developed compound with high affinity and selectivity for PDE10A, using PET with [(11)C]T-773 in nonhuman primates. Two 123-min dynamic PET measurements were performed on three female rhesus monkeys, once at baseline and again after intravenous administration of different doses of TAK-063 (0.2-1.6 mg/kg). Total distribution volume (V(T)) was calculated with a two-tissue compartment model using metabolite-corrected plasma input. Although the in vitro autoradiography did not show high specific binding to [(11)C]T-773 in the cerebellum, V(T) in the cerebellum decreased after TAK-063 treatment. The specific binding to PDE10A (V(S)) was calculated as the difference of the V(T) between the target regions and the cerebellum. PDE10A occupancy was calculated as the percent change of V(S). The average PDE10A occupancy of the caudate nucleus and putamen was 35.2% at 0.2 mg/kg and 83.2% at 1.6 mg/kg. In conclusion, this nonhuman primate PET study demonstrated that [(11)C]T-773 is useful to estimate the PDE10A occupancy by TAK-063 in the striatum although there is in vivo interaction of the uptake between [(11)C]T-773 and TAK-063 in the cerebellum. These results warrant further clinical occupancy study for TAK-063. PMID- 26878352 TI - Factors affecting the polarity and magnitude of photoresponse of transient photodetectors. AB - The addition of an insulating layer (I) between one of the metal electrodes (M) and the photoactive semiconducting layer (S) in a standard organic MSM solar cell architecture changes the DC photocurrent response into a strong transient signal. Such a device can, in simple terms, be thought of as a charging voltage source (S) in contact with a charging capacitor (I). The magnitude of the photocurrent signal can be strongly enhanced through the intimate contact of the active layer with the insulating layer, if the various pre-polarizations within the device act synergically. In this study, the effect of the built-in potentials within the device on the polarity and magnitude of the photocurrent response is studied using the well-characterized bulk heterojunction blend system of poly(3 hexylthiophenone):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCBM) as the semiconductor layer, and an ionic liquid as the insulating layer. This study shows that the polarity of the response is not simply determined by the energy level difference of the outer electrodes, but through a delicate interplay of all the energy levels in the device. Furthermore, these observations could be reproduced for devices with a solid-state insulator layer, where possible side effects of the ionic liquid, such as swelling and doping, could be considered absent. PMID- 26878353 TI - Self-assembly of Pd2L2 Metallacycles Owning Diversely Functionalized Racemic Ligands. AB - We present herein the efficient palladium(II)-directed self-assembly in water of a series of nine new diversely functionalized metallacycles, owning hydroxy/alkoxycarbonyl/azidoalkyl exo pendant groups attached to ditopic N monoalkyl/aryl-4,4'-bipyridinium/2,7-diazapyrenium ligands. The highly convergent and versatile synthetic route for the ligands uses the Zincke reaction between (dinitrophenyl)bipyridinium/diazapyrenium salts and racemic amines as the key step. The stereochemical outcome of the self-assembly of the Pd2L2 species is discussed on the basis of density functional theory quantum-chemical calculations. PMID- 26878355 TI - Nanomolar colorimetric quantitative detection of Fe3+ and PPi with high selectivity. AB - A novel rhodamine and 8-hydroxyquinoline-based derivative was synthesized, which is shown to act as a colorimetric chemosensor for Fe(3+) in aqueous solution with high selectivity over various environmentally and biologically relevant metal ions and anions with a distinct color change from colorless to pink in very fast response time (<1 min). Fe(3+) can be detected quantitatively in the concentration range from 6.7 to 16 MUM and the detection limit (LOD) on UV-vis response of the sensor can be as low as 15 nM. The 'in situ' prepared Fe(3+) complex (1?Fe) showed high selectivity toward PPi against many common anions, and sensitivity (the LOD can be as low as 71 nM). In addition, both the chemosensor and the 'in situ' prepared Fe(3+) complex are reusable for the detection of Fe(3+) and PPi respectively. PMID- 26878356 TI - Application of longan shell as non-conventional low-cost adsorbent for the removal of cationic dye from aqueous solution. AB - With simple physical treatment, adsorption potential of longan shell for the methylene blue (MB) from aqueous solution was studied as a low-cost material under the conditions of adsorbent dosage (1-6 g/L), initial solution pH (2-12), contact time (5-180 min), temperature (293, 313, 313 K) and initial dye concentration (100-500 mg/L). The SEM images and FTIR spectra of longan shell before and after dye adsorption were analyzed to understand the adsorption process of MB onto longan shell. The kinetic data and the equilibrium data were simulated by different kinetic and isotherm models, respectively. The results showed that the adsorption process was well described by the pseudo-second-order kinetic model, and the experimental equilibrium data were better fit to Langmuir equation than Freundlich equation with the maximum adsorption capacity of 141.04 mg/g. In addition, main activation parameters (E(a), DeltaH(#), DeltaS(#) and DeltaG(#)) and thermodynamic parameters (DeltaG degrees , DeltaH degrees and DeltaS degrees ) of the absorption process were also determined. PMID- 26878357 TI - Osmotic diuresis with SGLT2 inhibition: analysis of events related to volume reduction in dapagliflozin clinical trials. AB - OBJECTIVE: Dapagliflozin reduces hyperglycemia in type 2 diabetes mellitus (T2DM) and lowers blood pressure, at least in part, secondary to mild diuresis consequent to dapagliflozin-induced glucosuria. While blood-pressure lowering may contribute to cardiovascular risk reduction, dapagliflozin-induced diuresis may potentially contribute to adverse events (AEs) of volume reduction. The present analysis compared the frequency of AEs of volume reduction between dapagliflozin and placebo. METHODS: Pooled data were assessed from 13 placebo-controlled dapagliflozin clinical trials <=24 weeks in patients with T2DM, overall, and in those at risk (aged >=65y, estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2), or on antihypertensive therapy). Longer-term (<=104 weeks) data were available for 9 of these trials. RESULTS: The frequency of patients experiencing >=1 AE of volume reduction over 24 weeks was low overall; 27/2360 (1.1%) with dapagliflozin 10 mg and 17/2295 (0.7%) with placebo; and slightly more frequent in patients >=65 years (11/665 [1.7%] and 6/711 [0.8%], respectively) and in patients receiving loop diuretics (6/236 [2.5%] and 4/267 [1.5%], respectively). Over 104 weeks, AEs of volume reduction occurred in 38/2026 (1.9%) with dapagliflozin 10 mg and in 27/1956 (1.4%) with placebo; serious AEs of volume reduction in 4/2026 (0.2%) and 6/1956 (0.3%), respectively; and 2 patients in each group discontinued therapy due to these AEs. Dapagliflozin versus placebo incidence rate ratios did not suggest any meaningful increase in frequency of these AEs with dapagliflozin 10 mg, either overall or in those at risk. Although mean eGFR declined by 4.2 ml/min/1.73 m(2) within the first week of dapagliflozin therapy, thereafter eGFR gradually recovered to baseline levels by 104 weeks (mean change from baseline +0.02 mL/min/1.73 m(2); 95%CI: -0.9, 1.0). CONCLUSION: No meaningful increase in frequency of AEs of volume reduction occurred with dapagliflozin 10 mg in patients with T2DM, either overall, or in those at increased risk of these events. However, caution should nevertheless be exercised when prescribing dapagliflozin to elderly patients, those with reduced eGFR, and those receiving antihypertensive medication. PMID- 26878358 TI - Dieulafoy lesion of the gallbladder presenting with bleeding and a pseudo-mirizzi syndrome: A case report and review of the literature. AB - INTRODUCTION: Gastrointestinal bleeding can have significant morbidity and mortality. Pathological processes that cause it are diverse, and timely investigation and management are vital. Dieulafoy lesions are a rare cause of gastrointestinal bleeding and here we describe a case of a gallbladder dieulafoy lesion causing gastrointestinal bleeding. PRESENTATION OF CASE: Recently discharged from hospital following an open anterior resection and loop ileostomy for diverticular disease, an 84-year-old female re-presented with lower abdominal pain associated with jaundice and lymphocytosis. Imaging demonstrated two possible rectal stump collections (treated with antibiotics), and heterogeneous material in the gallbladder. The patient deteriorated, developing melena, coffee ground vomitus and right upper quadrant pain. Investigation sourced the bleeding to the gallbladder that resolved following cholecystectomy, and histopathology was consistent with a dieulafoy lesion. The patient made a full recovery. DISCUSSION: Dieulafoy lesions have rarely been reported in the gallbladder, and as such can be an occult source of massive gastrointestinal bleeding. It should be considered where gastrointestinal bleeding accompanies jaundice and abdominal pain. CONCLUSION: This case highlights that dieulafoy lesions can occur in the gallbladder. Massive gastrointestinal bleeding can occur within the gallbladder, and a gallbladder dieulafoy lesion should be considered as a potential cause of such, especially when a source has not been identified on endoscopy. It also demonstrates the effectiveness of cholecystectomy as a definitive management strategy. PMID- 26878359 TI - Nutrient removal by up-scaling a hybrid floating treatment bed (HFTB) using plant and periphyton: From laboratory tank to polluted river. AB - Planted floating treatment bed (FTB) is an innovative technique of removing nutrients from polluted water but limited in deep water and cold seasons. Periphyton was integrated into FTB for a hybrid floating treatment bed (HFTB) to improve its nutrient removal capacity. To assess its potential for treating nutrient-polluted rivers, HFTB was up-scaled from 5L laboratory tanks to 350L outdoor tanks and then to a commercial-scale 900m section of polluted river. Plants and periphyton interacted in HFTB with periphyton limiting plant root growth and plants having shading effects on periphyton. Non-overlapping distribution of plants and periphyton can minimize the negative interactions in HFTB. HFTB successfully kept TN and TP of the river at less than 2.0 and 0.02mgL( 1), respectively. This study indicates that HFTB can be easily up-scaled for nutrients removal from polluted rivers in different seasons providing a long term, environmentally-friendly method to remediate polluted ecosystems. PMID- 26878360 TI - Optimization of phenol degradation by the microalga Chlorella pyrenoidosa using Plackett-Burman Design and Response Surface Methodology. AB - Statistical optimization designs were used to optimize the phenol degradation using Chlorella pyrenoidosa. The important factor influencing phenol degradation was identified by two-level Plackett-Burman Design (PBD) with five factors. PBD determined the following three factors as significant for phenol degradation viz. algal concentration, phenol concentration and reaction time. CCD and RSM were applied to optimize the significant factors identified from PBD. The results obtained from CCD indicated that the interaction between the concentration of algae and phenol, phenol concentration and reaction time and algal concentration and reaction time affect the phenol degradation (response) significantly. The predicted results showed that maximum phenol degradation of 97% could be achieved with algal concentration of 4g/L, phenol concentration of 0.8g/L and reaction time of 4days. The predicted values were in agreement with experimental values with coefficient of determination (R(2)) of 0.9973. The model was validated by subsequent experimentations at the optimized conditions. PMID- 26878361 TI - Complementary surface charge for enhanced capacitive deionization. AB - Commercially available activated carbon cloth electrodes are treated using nitric acid and ethylenediamine solutions, resulting in chemical surface charge enhanced carbon electrodes for capacitive deionization (CDI) applications. Surface charge enhanced electrodes are then configured in a CDI cell to examine their salt removal at a fixed charging voltage and both reduced and opposite polarity discharge voltages, and subsequently compared to the salt removal of untreated electrodes. Substantially improved salt removal due to chemical surface charge and the use of a discharge voltage of opposite sign to the charging voltage is clearly demonstrated in these CDI cycling tests, an observation which for the first time validates both enhanced CDI and extended-voltage CDI effects predicted by the Donnan model [Biesheuvel et al., Colloids Interf. Sci. Comm., 10.1016/j.colcom.2015.12.001 (2016)]. Our experimental and theoretical results demonstrate that the use of carbon electrodes with optimized chemical surface charge can extend the CDI working voltage window through discharge voltages of opposite sign to the charging voltage, which can significantly enhance the salt adsorption capacity of CDI electrodes. Thus, in addition to carbon pore size distribution, chemical surface charge in carbon micropores is considered foundational for salt removal in CDI cells. PMID- 26878362 TI - Role of Collagen Conduit With Duloxetine and/or Pregabalin in the Management of Partial Peripheral Nerve Injury. AB - PURPOSE: The objective of this study was to investigate the analgesic effect of a collagen conduit (Neuragen, Integra LifeSciences Corp, Plainsboro, NJ) using duloxetine (Cymbalta, Lilly, Indianapolis, IN) with or without pregabalin (Lyrica, Pfizer, NY) on pain induced by partial sciatic nerve transection in a rat model. MATERIAL AND METHODS: Adult male Sprague-Dawley rats were divided into 5 groups (n = 10 per group): group 1, nerve damage with no treatment; group 2, nerve damage treated with the application of a collagen conduit and saline; group 3, nerve damage treated with the application of a collagen conduit and duloxetine; group 4, nerve damage treated with the application of a collagen conduit and pregabalin; and group 5, nerve damage treated with the application of a collagen conduit and pregabalin plus duloxetine. Pain levels were evaluated by responses to mechanical and thermal stimuli at baseline before and 3 and 7 days after surgery. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF) levels were evaluated in blood, sciatic nerve, and dorsal root ganglion samples collected 7 days after surgery. RESULTS: The group treated with the collagen conduit and pregabalin exhibited markedly less pain 7 days postoperatively in response to mechanical and thermal stimuli compared with the other groups. IL-10 levels were considerably increased in the group treated with pregabalin. The groups treated with a collagen conduit and duloxetine and a combination of pregabalin and duloxetine also exhibited markedly less pain in response to mechanical and thermal stimuli 7 days after surgery compared with the group that had only nerve injury. The decrease in pain using duloxetine was not as robust but was associated with a decrease of TNF-alpha. The combination of pregabalin and duloxetine resulted in a substantial decrease in IL-6. CONCLUSION: Using a collagen conduit and duloxetine, pregabalin, and their combination helped alleviate neuropathic pain. The mechanism of action might be associated, at least in part, to cytokines. PMID- 26878363 TI - Lifelong Learning and Professional Development. PMID- 26878364 TI - Temporomandibular Joint Ankylosis Can Be Successfully Treated With TMJ Concepts Patient-Fitted Total Joint Prosthesis and Autogenous Fat Grafts. AB - PURPOSE: To measure and identify factors associated with treatment outcomes for patients with temporomandibular joint (TMJ) ankylosis treated with TMJ Concepts patient-fitted total joint prostheses and autogenous fat grafts. PATIENTS AND METHODS: This retrospective cohort study evaluated records of patients with TMJ ankylosis from a single private practice, treated from 1992 to 2011, who met the following inclusion criteria: 1) radiographic evidence of bony ankylosis, 2) limited incisal opening, 3) minimum of 12 months' follow-up, and 4) treatment with TMJ Concepts (Ventura, CA)/Techmedica (Camarillo, CA) total joint prostheses and fat grafts. For each patient, the number of previous TMJ surgical procedures, as well as the estimated age of ankylosis onset, age at surgery, and length of postoperative follow-up, was recorded. Subjective evaluations were made with Likert-like scales (from 0 to 10) for 1) TMJ pain, 2) headache and facial pain, 3) jaw function, 4) diet, and 5) disability. Objective evaluations included maximal incisal opening and excursion movements. Nonparametric statistics were used for analysis. RESULTS: There were 32 patients (22 female and 10 male patients) with 48 ankylosed TMJs (16 bilateral and 16 unilateral) in this study, with a mean age of 39 years (range, 11 to 68 years), 2 or more previous TMJ surgical procedures in 69%, and a mean follow-up period of 68 months (range, 12 to 168 months). Trauma was the major etiology of TMJ ankylosis, occurring in 17 of 32 patients (53%). The following improvements occurred: The median value for TMJ pain changed from 8.0 preoperatively to 1.5 at longest follow-up; headache, from 8 to 3.5; facial pain, from 8 to 4; jaw function, from 8 to 2.5; diet, from 7 to 3; and disability, from 7 to 1.5. The median incisal opening was 14.5 mm (interquartile range, 6.3 to 20 mm) preoperatively and 35 mm (interquartile range, 30 to 40 mm) at longest follow-up. The median left lateral excursion improved from 0.5 to 2 mm, and the median right lateral excursion improved from 1 to 1.3 mm. All of these improvements were highly significant (P < .001, Wilcoxon tests). Equally favorable outcomes were found in patients with 12 to 48 months of maximal follow-up and patients with more than 48 months of maximal follow-up. CONCLUSIONS: The treatment of TMJ ankylosis with the TMJ Concepts patient-fitted total joint prosthesis in combination with fat grafting around the articulation area of the prosthesis is a viable and predictable method for improving pain levels, function, and quality of life, as well as prevention of reankylosis of the TMJ. PMID- 26878365 TI - Two-Step Reconstruction of Non-Marginal Auricular Defects. AB - PURPOSE: Auricular reconstruction is an extensively discussed topic in facial reconstructive surgery and poses an immense challenge to the reconstructive surgeon. This report describes a 2-stage technique to repair non-marginal full thickness defects of the auricle. MATERIALS AND METHODS: Thirteen patients underwent surgery after partial to complete loss of the auricular concha using an improved and refined method. Tissue from the pre- and retroauricular regions was used to replace nonhelical auricular tissue loss in 2 surgical steps. All procedures were performed in an ambulatory setting using local anesthesia. RESULTS: All 13 patients (age range, 37 to 82 yr; mean age, 68 yr; 4 women and 9 men) had excellent esthetic outcomes with low surgical morbidity and were satisfied with the achieved results. No flap necrosis was observed. Auricular vertical and horizontal dimensions changed minimally (0 to 4 mm). A tension-free closure of the donor-site defects could be achieved primarily. CONCLUSION: The present method uses 2 separate donor sites to reconstruct centrally located full thickness defects of the auricle. It is straightforward to perform, minimizes the surgical steps required, shows excellent outcomes, and allows easier closure of the donor site because of the distribution of the harvested tissue. PMID- 26878366 TI - Supported liquid extraction (SLE) for the analysis of methylamphetamine, methylenedioxymethylamphetamine and delta-9-tetrahydrocannabinol in oral fluid and blood of drivers. AB - Since 2006, the South Australian Government has been conducting roadside oral fluid testing of drivers for the illicit drugs methylamphetamine (MA), methylenedioxymethylamphetamine (MDMA) and Delta(9)-tetrahydrocannabinol (THC) using the Securetec Drugwipe II Twin and Alere DDS 805 AP saliva collection kit. Forensic Science South Australia carries out the confirmatory analysis by LC/MS for the positive test results of oral fluid roadside testing along with the pre screened ELISA positive road traffic accident blood samples. The number of blood and oral fluid samples received in the laboratory has been steadily increasing during this time, and over 10,000 samples were received in 2014. The proportion of positive results from these samples has also been increasing over the decade of driver drug testing, and this data is presented. A simple and efficient method has been developed for the analysis of the three drugs using Biotage Isolute((r)) SLE+ 96-well plates. Sample preparation included 1:1 dilution with a dilute ammonia solution for buffered oral fluids (1:3 dilution for blood samples), and addition of deuterated internal standards. Samples were loaded onto the phase, left to absorb for 5min then eluted with methyl t-butyl ether (MTBE). The samples were evaporated and reconstituted in methanol. LC/MS analysis was performed on an AB Sciex 5500 Q-Trap in positive ion mode, monitoring 3 transitions for each analyte. Separation was achieved on a Restek Ultrabiphenyl 50*2.1mm column with a gradient system of acetonitrile/0.1% formic acid over 5min. Method validation and recoveries were carried out on drug free ante mortem blood and DDS buffer solution provided by Alere, Australia. Recoveries above 80% were achieved for MA and MDMA at a concentration of 25ng/mL, whilst recoveries of greater than 65% were achieved for THC at 4.5ng/mL. Accuracy and precision were acceptable down to the LLOQ for all three analytes (5, 5 and 1ng/mL for MA, MDMA and THC, respectively). Mean matrix effects were 1.0, 0.97 and 0.78 in DDS buffer and 0.96, 0.96 and 0.62 in blood for MA, MDMA and THC, respectively. Linearity was achieved up to 1250ng/mL for MA and MDMA, and 112ng/mL for THC (r(2)>0.999 for all analytes). The method is designed for easy transfer to an automated liquid handling platform. PMID- 26878367 TI - Activation of NADPH-recycling systems in leaves and roots of Arabidopsis thaliana under arsenic-induced stress conditions is accelerated by knock-out of Nudix hydrolase 19 (AtNUDX19) gene. AB - NADPH is an important cofactor in cell growth, proliferation and detoxification. Arabidopsis thaliana Nudix hydrolase 19 (AtNUDX19) belongs to a family of proteins defined by the conserved amino-acid sequence GX5-EX7REUXEEXGU which has the capacity to hydrolyze NADPH as a physiological substrate in vivo. Given the importance of NADPH in the cellular redox homeostasis of plants, the present study compares the responses of the main NADPH-recycling systems including NADP isocitrate dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), 6 phosphogluconate dehydrogenase (6PGDH) and NADP-malic enzyme (ME) in the leaves and roots of Arabidopsis wild-type (Wt) and knock-out (KO) AtNUDX19 mutant (Atnudx19) plants under physiological and arsenic-induced stress conditions. Two major features were observed in the behavior of the main NADPH-recycling systems: (i) under optimal conditions in both organs, the levels of these activities were higher in nudx19 mutants than in Wt plants; and, (ii) under 500MUM AsV conditions, these activities increase, especially in nudx19 mutant plants. Moreover, G6PDH activity in roots was the most affected enzyme in both Wt and nudx19 mutant plants, with a 4.6-fold and 5.0-fold increase, respectively. In summary, the data reveals a connection between the absence of chloroplastic AtNUDX19 and the rise in all NADP-dehydrogenase activities under physiological and arsenic-induced stress conditions, particularly in roots. This suggests that AtNUDX19 could be a key factor in modulating the NADPH pool in plants and consequently in redox homeostasis. PMID- 26878368 TI - The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis inducing ligand (TRAIL) within the vasculature: A review of the evidence. AB - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that belongs to the tumour necrosis factor (TNF) cytokine superfamily. TRAIL is expressed by numerous cell types including vascular cells, immune cells and adipocytes. Although originally thought to induce apoptosis in malignant or transformed cells only, it is now known that TRAIL can bind up to 5 distinct receptors to activate complex signalling pathways, and is capable of exerting pleiotropic effects in non-transformed cells. In this respect, a number of clinical and animal studies point to the potential vasoprotective influence of TRAIL, with TRAIL deficiency being linked to accelerated atherosclerosis and vascular calcification. Moreover, exogenous TRAIL administration has been shown to exhibit anti-atherosclerotic activity in-vivo. In-vitro studies on TRAIL in this context have yielded conflicting results however, with evidence of both pro atherogenic and vasoprotective effects ascribed to TRAIL. Notwithstanding these various studies, mechanistic information on the precise nature of TRAIL-mediated injury/protection within the vasculature, as well as the identity of the downstream molecular/cellular targets of TRAIL, is still quite limited. In this review, we will summarize our current knowledge of TRAIL regulation, signalling mechanisms, and its apparent involvement in CVD pathogenesis as a prelude to examining the existing evidence for TRAIL-mediated vasoprotection. To this end, extensive in vitro, in vivo, and clinical studies will be reviewed and critical findings highlighted. PMID- 26878369 TI - Porcine xenograft treatment of superficial partial-thickness burns in paediatric patients. AB - OBJECTIVE: Porcine xenograft (PX) has become a valuable part of the armamentarium of treatment options in a US paediatric burn centre. The use in adult patients has been well described in the burn literature, but there is minimal literature describing its use in children. The objective of this article is to describe a three-years' experience with PX use in paediatric burns. METHOD: A retrospective medical record review of patients with superficial partial-thickness burns treated with PX admitted to a paediatric burn centre between February 2009 and November 2012. RESULTS: A total of 164 patients met the inclusion criteria. Burn total body surface area (TBSA) ranged from 0.5% to 28%. After the placement of PX, significant decreases were seen in the need for narcotic analgesics and burn dressing changes. Only four of 164 patients (2.4%) developed infections, although only one of these infections was at the site of the xenograft. CONCLUSION: PX appears to reduce pain and eliminate the need for procedural intravenous sedation in many patients. This can make burn wound care more child-friendly and shorten hospital length of stay. The complication rate is low and manageable. The authors believe that PX is an effective and safe treatment for superficial partial thickness burns in children. DECLARATION OF INTEREST: P. M.Glat, is a paid consultant and speaker for Molnlycke Health Care, the manufacturer of EZ Derm. PMID- 26878370 TI - The presence of biofilm structures in atherosclerotic plaques of arteries from legs amputated as a complication of diabetic foot ulcers. AB - OBJECTIVE: Atherosclerosis, rather than microcirculatory impairment caused by endothelial cell dysfunction, is the main driver of circulatory compromise in patients with diabetic limbs. The presence of atherosclerotic plaque at the trifurcation is a significant contributor to amputation of diabetic legs. The presence of bacteria and other microorganisms in atherosclerotic plaque has long been known, however, the cause of chronic inflammation and the role of bacteria/viruses in atherosclerosis have not been studied in detail. The objective of this study was to clarify the cause of the chronic inflammation within atherosclerotic plaques, and determine if any bacteria and/or viruses are involved in the inflammatory pathway. METHOD: This study uses fluorescence microscopy and fluorescence in-situ hybridisation (FISH) to identify components of biofilm in atherosclerotic arteries. These tools are also used to identify individual bacteria, and determine the architectural spatial location within the atherosclerotic plaque where the bacteria can be found. RESULTS: The results indicate that the presence of biofilms in grossly involved arteries may be an important factor in chronic inflammatory pathways of atherosclerotic progression, in the amputated limbs of patients with diabetic foot ulcers and vascular disease. CONCLUSION: While the presence of bacterial biofilm structures in atherosclerotic plaque does not prove that biofilm is the proximate cause of atherosclerosis, it could contribute to the persistent inflammation associated with it. Second, the synergistic relationship between the atherosclerotic infection and the diabetic foot ulcer may ultimately contribute to higher amputation rates in diabetics. DECLARATION OF INTEREST: RAW and RDW have equity interest in PathoGenius, a clinical laboratory using DNA to identify microbes. PMID- 26878371 TI - Healing of chronic sickle cell disease-associated foot and ankle wounds using transdermal continuous oxygen therapy. AB - OBJECTIVE: Sickle cell disease (SCD) is a complex cause of capillary stasis that can lead to lower extremity venous ulcers. Since SCD is characterised by impaired oxygen delivery that can be exacerbated by lower extremity venous stasis, we sought to determine if direct delivery of oxygen to a lower extremity ulcer associated with SCD could augment healing. METHOD: We performed a pilot study of a portable device that delivers oxygen directly to the wound site to assess this possibility. The device was assessed in a single patient with three longstanding wounds of the lower extremities associated with SCD: the lateral right ankle, the medial aspect of the distal left leg, and the dorsal left foot. The left leg and left foot wounds received 15 weeks of treatment each. RESULTS: Both left lower extremity wounds healed, and neither wound has relapsed in the 42 months since the treatment was completed. At 36 months from the completion of treatment, the patient presented to the hospital with renal failure, and with the 27 days of complete bed rest and wound elevation, the right ankle wound shrunk to 55% of the original wound surface area. Transdermal oxygen appears to have assisted in healing and to have provided a sustained benefit that has delayed relapse of the two SCD-associated leg ulcers that received an extended course of treatment. Similarly, complete bed rest appears to aid in the healing of SCD-associated leg ulcers. Further study is needed to determine the mechanism of action and the optimal method of use of the transdermal continuous oxygen delivery device for SCD-associated lower extremity ulcers. DECLARATION OF INTEREST: No competing financial interests exist for any author. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article. PMID- 26878373 TI - Challenging present concepts in compression therapy: static stiffness index is not consistent and not clinically relevant. AB - Once a circumferential force is delivered to a limb by a compression device, assuming the tension within the device remains constant, any change in the total force is dependent upon a change in circumference of the limb, with the rate of change (excluding fabric creep) being dependent on the stress strain curve of the device. This article addresses the pre-conceived and well-accepted principle that interface compression delivered by a compression device substantially increases with the position of the limb, based on the positions of sitting (non-weight bearing) to standing and/or during muscle activity (ankle dorsiflexion). Using engineering parameters and clinical measurements, the authors demonstrate that changes in interface pressure are minimal if any, and that the current concept should be modified accordingly. Declaration of interest: This study was sponsored by Carolon. L. Reid, and S. Kravitz are employees of Carolon. M. Hegarty-Craver has received monetary compensation as a researcher for Carolon. PMID- 26878374 TI - Medications for Meniere's disease? PMID- 26878375 TI - Pooled analysis of the evidence for open cavity, combined approach and reconstruction of the mastoid cavity in primary cholesteatoma surgery. AB - BACKGROUND: Cholesteatoma is keratinising epithelium within the middle-ear cleft or mastoid. This disease destroys the peripheral organs of balance and hearing, with possible intracranial sequelae. The management of cholesteatoma is surgical and the primary aim is to remove the disease and prevent recurrence. Secondary aims are to obtain a non-discharging, hearing ear. Cholesteatoma surgery falls into two broad categories: open cavity surgery and combined approach surgery. A third surgical category is reconstruction of an open mastoid cavity after open surgery. This study performed a pooled analysis of the worldwide literature to compare the rates of cholesteatoma not being cured (i.e. recidivism), ear discharge and hearing change among open cavity, combined approach and reconstruction mastoid surgery for primary cholesteatoma. METHODS: A literature search for all types of cholesteatoma surgery in the PubMed, Google Scholar and Medline databases and in published conference proceedings was undertaken. RESULTS: There was no level 1 evidence for the best method of primary cholesteatoma surgery. The highest evidence level found (level 2; 5366 patients) shows no difference in hearing change or discharge rate between open and combined approach surgery; however, these methods fail to cure the cholesteatomas in 16.0 per cent and 29.4 per cent of cases, respectively. In a total of 640 patients, reconstruction and/or repair mastoid surgery using a variety of non-comparable techniques had a failure rate of between 5.3 per cent and 20 per cent. CONCLUSION: The available evidence suggests that reconstruction of the posterior canal wall and/or obliteration of the mastoid may be the best surgical treatment alternative. This technique appears to provide the lowest recidivism rate combined with a low post-operative ear discharge rate. PMID- 26878376 TI - You can't pay me to quit: the failure of financial incentives for smoking cessation in head and neck cancer patients. AB - OBJECTIVE: A prospective randomised study was conducted at a tertiary care hospital to evaluate the effects of financial incentives for smoking cessation targeted at a high-risk population. METHODS: Patients with a past history of head and neck cancer were voluntarily enrolled over a two-year period. They were randomised to a cash incentives or no incentive group. Subjects were offered enrolment in smoking cessation courses. Smoking by-product levels were assessed at 30 days, 3 months and 6 months. Subjects in the incentive group received $150 if smoking cessation was confirmed. RESULTS: Over 2 years, 114 patients with an established diagnosis of head and neck cancer were offered enrolment. Twenty-four enrolled and 14 attended the smoking cessation classes. Only two successfully quit smoking at six months. Both these patients were in the financially incentivised group and received $150 at each test visit. CONCLUSION: Providing a financial incentive for smoking cessation to a population already carrying a diagnosis of head and neck cancer in order to promote a positive behaviour change was unsuccessful. PMID- 26878377 TI - Outcome evaluation of clarithromycin, metronidazole and lansoprazole regimens in Helicobacter pylori positive or negative children with resistant otitis media with effusion. PMID- 26878378 TI - Double seal technique to obliterate the eustachian tube orifice: a novel method for the treatment of recalcitrant cerebrospinal fluid leak. PMID- 26878379 TI - Choosing the safest acute therapy during chronic migraine prophylactic treatment: pharmacokinetic and pharmacodynamic considerations. AB - INTRODUCTION: Drugs used in the treatment of migraine have been reported to be highly associated with the occurrence of clinically significant drug-drug interactions (DDIs). Multiple drug therapy regimens are used for migraine treatment, particularly for chronic migraine. In fact, additional pharmacological agents are usually administered during an acute migraine attack in patients chronically treated with the prophylactic therapy. The variety of drugs available for migraine prophylactic and acute treatment, and consequently their pharmacological interactions, might complicate the choice of a safe combination therapy. AREAS COVERED: This study discusses the prophylactic-acute DDIs from a pharmacokinetic and pharmacodynamic perspective, particularly interactions between antiepileptic drugs, tricyclic antidepressants, beta-blockers, calcium channel blockers, triptans, nonsteroidal anti-inflammatory drugs and ergot derivatives. The available online tools have been used to evaluate the clinically significant DDIs. EXPERT OPINION: The interactions between different drugs might be accurately predicted by the huge and detailed knowledge about the molecular pathways involved in pharmacodynamics and pharmacokinetics. Pharmacogenomic research has shed further light onto the mechanisms involved in the inter individual variation in drug response and DDIs. Based on this knowledge, this paper will provide suggestions to improve the appropriateness of the drug choice in the prescription of preventative and acute migraine medications. PMID- 26878380 TI - Switching on After Nine: Black gay-identified men's perceptions of sexual identities and partnerships in South African towns. AB - There is considerable diversity, fluidity and complexity in the expressions of sexuality and gender among men who have sex with men (MSM). Some non-gay identified MSM are known colloquially by gay-identified men in Mpumalanga, Province, South Africa, as 'After-Nines' because they do not identify as gay and present as straight during the day but also have sex with other men at night. Based on, key informant interviews and focus group discussions in two districts in Mpumalanga, we explored Black gay-identified men's perceptions of and relationships with After-Nine men, focusing on sexual and gender identities and their social consequences. Gay-identified men expressed ambivalence about their After-Nine partners, desiring them for their masculinity, yet often feeling dissatisfied and exploited in their relationships with them. The exchange of sex for commodities, especially alcohol, was common. Gay men's characterisation of After-Nines as men who ignore them during the day but have sex with them at night highlights the diversity of how same-sex practicing men perceive themselves and their sexual partners. Sexual health promotion programmes targeting 'MSM' must understand this diversity to effectively support the community in developing strategies for reaching and engaging different groups of gay and non-gay identified men. PMID- 26878381 TI - Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain. AB - Real-time activity measurements from multiple specific cell populations and projections are likely to be important for understanding the brain as a dynamical system. Here we developed frame-projected independent-fiber photometry (FIP), which we used to record fluorescence activity signals from many brain regions simultaneously in freely behaving mice. We explored the versatility of the FIP microscope by quantifying real-time activity relationships among many brain regions during social behavior, simultaneously recording activity along multiple axonal pathways during sensory experience, performing simultaneous two-color activity recording, and applying optical perturbation tuned to elicit dynamics that match naturally occurring patterns observed during behavior. PMID- 26878384 TI - How self-reflection and self-certainty are related to neurocognitive functioning: an examination of cognitive insight in bipolar disorder. AB - INTRODUCTION: The pattern of associations between clinical insight, cognitive insight, and neurocognitive functioning was assessed in bipolar disorder patients. METHODS: Data from 42 bipolar disorder patients were examined. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS). The BCIS is a 15-item self-report instrument consisting of two subscales, self reflectiveness and self-certainty. Clinical insight was measured by the use of the item G12 of the Positive and Negative Syndrome Scale. Neurocognitive functioning was assessed using the International Society for Bipolar Disorders Battery for Assessment of Neurocognition. RESULTS: Correlation analyses revealed significant positive associations between self-reflectiveness and speed of processing, attention, working memory, visual learning, and reasoning and problem solving. The subscale self-certainty was negatively correlated to working memory, however, this correlation disappeared when we controlled for confounding variables. No correlations between clinical insight and neurocognition were found. In addition, there was no association between cognitive insight and clinical insight. CONCLUSION: Better neurocognitive functioning was more related to higher levels of self-reflectiveness than to diminished self-certainty. PMID- 26878383 TI - Apollo-NADP(+): a spectrally tunable family of genetically encoded sensors for NADP(+). AB - NADPH-dependent antioxidant pathways have a critical role in scavenging hydrogen peroxide (H2O2) produced by oxidative phosphorylation. Inadequate scavenging results in H2O2 accumulation and can cause disease. To measure NADPH/NADP(+) redox states, we explored genetically encoded sensors based on steady-state fluorescence anisotropy due to FRET (fluorescence resonance energy transfer) between homologous fluorescent proteins (homoFRET); we refer to these sensors as Apollo sensors. We created an Apollo sensor for NADP(+) (Apollo-NADP(+)) that exploits NADP(+)-dependent homodimerization of enzymatically inactive glucose-6 phosphate dehydrogenase (G6PD). This sensor is reversible, responsive to glucose stimulated metabolism and spectrally tunable for compatibility with many other sensors. We used Apollo-NADP(+) to study beta cells responding to oxidative stress and demonstrated that NADPH is significantly depleted before H2O2 accumulation by imaging a Cerulean-tagged version of Apollo-NADP(+) with the H2O2 sensor HyPer. PMID- 26878382 TI - Single-molecule imaging of non-equilibrium molecular ensembles on the millisecond timescale. AB - Single-molecule fluorescence microscopy is uniquely suited for detecting transient molecular recognition events, yet achieving the time resolution and statistics needed to realize this potential has proven challenging. Here we present a single-molecule imaging and analysis platform using scientific complementary metal-oxide semiconductor (sCMOS) detectors that enables imaging of 15,000 individual molecules simultaneously at millisecond rates. This system enabled the detection of previously obscured processes relevant to the fidelity mechanism in protein synthesis. PMID- 26878385 TI - mTOR inhibition decreases SOX2-SOX9 mediated glioma stem cell activity and temozolomide resistance. AB - BACKGROUND: SOX2 and SOX9 are commonly overexpressed in glioblastoma, and regulate the activity of glioma stem cells (GSCs). Their specific and overlapping roles in GSCs and glioma treatment remain unclear. METHODS: SOX2 and SOX9 levels were examined in human biopsies. Gain and loss of function determined the impact of altering SOX2 and SOX9 on cell proliferation, senescence, stem cell activity, tumorigenesis and chemoresistance. RESULTS: SOX2 and SOX9 expression correlates positively in glioma cells and glioblastoma biopsies. High levels of SOX2 bypass cellular senescence and promote resistance to temozolomide. Mechanistic investigations revealed that SOX2 acts upstream of SOX9. mTOR genetic and pharmacologic (rapamycin) inhibition decreased SOX2 and SOX9 expression, and reversed chemoresistance. CONCLUSIONS: Our findings reveal SOX2-SOX9 as an oncogenic axis that regulates stem cell properties and chemoresistance. We identify that rapamycin abrogate SOX protein expression and provide evidence that a combination of rapamycin and temozolomide inhibits tumor growth in cells with high SOX2/SOX9. PMID- 26878386 TI - A serum-circulating long noncoding RNA signature can discriminate between patients with clear cell renal cell carcinoma and healthy controls. AB - Serum biomarkers have not been fully incorporated into clinical use for the diagnosis of renal cell carcinoma (RCC). The recent discovery of long noncoding RNAs (lncRNAs), which have been reported in a variety of cancer types, suggested a promising new class of biomarkers for tumour diagnosis. The aim of our study was to evaluate whether the levels of circulating lncRNAs could be used as a tumour marker to discriminate between clear cell RCC (ccRCC) patients and healthy controls. Serum samples were collected from 71 ccRCC patients including 62 age- and sex-matched healthy controls and 8 patients with benign renal tumours. Eighty two cancer-associated lncRNAs were assessed by reverse transcription and quantitative polymerase chain reaction in paired tissues and serum. A 5-lncRNA signature, including lncRNA-LET, PVT1, PANDAR, PTENP1 and linc00963, were identified and validated in the training set and testing set, respectively. The receiver operating characteristic curves for this serum 5-lncRNA signature were 0.900 and 0.823 for the two sets of serum samples. Moreover, five-minus-one lncRNA signatures demonstrated that none of the lncRNAs had a higher area under the curve than the others in either set. A risk model for the serum 5-lncRNA signature also determined that benign renal tumours can be distinguished from ccRCC samples. This work may facilitate the detection of ccRCC and serve as the basis for further studies of the clinical value of serum lncRNAs in maintaining surveillance and forecasting prognosis. PMID- 26878388 TI - Identification of differentially expressed miRNAs in individual breast cancer patient and application in personalized medicine. AB - MicroRNAs (miRNAs) have key roles in breast cancer progression, and their expression levels are heterogeneous across individual breast cancer patients. Traditional methods aim to identify differentially expressed miRNAs in populations rather than in individuals and are affected by the expression intensities of miRNAs in different experimental batches or platforms. Thus it is urgent to conduct miRNA differential expression analysis at an individual level for further personalized medicine research. We proposed a straightforward method to determine the differential expression of each miRNA in an individual patient by utilizing the reversal expression order of miRNA pairs between two conditions (cancer and normal tissue). We applied our method to breast cancer miRNA expression profiles from The Cancer Genome Atlas and two other independent data sets. In total, 292 miRNAs were differentially expressed in individual breast cancer patients. Using the differential expression profile of miRNAs in individual patients, we found that the deregulations of miRNA tend to occur in specific breast cancer subtypes. We investigated the coordination effect between the miRNA and its target, based on the hypothesis that one gene function can be changed by copy number alterations of the corresponding gene or deregulation of the miRNA. We revealed that patients exhibiting an upregulation of hsa-miR-92b and patients with deletions of PTEN did not tend to overlap, and hsa-miR-92b and PTEN coordinately regulated the pathway of 'cell cycle' and so on. Moreover, we discovered a new prognostic signature, hsa-miR-29c, whose downregulation was associated with poor survival of breast cancer patients. PMID- 26878387 TI - Dietary and pharmacological modification of the insulin/IGF-1 system: exploiting the full repertoire against cancer. AB - As more and more links between cancer and metabolism are discovered, new approaches to treat cancer using these mechanisms are considered. Dietary restriction of either calories or macronutrients has shown great potential in animal studies to both reduce the incidence and growth of cancer, and to act synergistically with other treatment strategies. These studies have also shown that dietary restriction simultaneously targets many of the molecular pathways that are targeted individually by anticancer drugs. The insulin/insulin-like growth factor-1 (IGF-1) system has thereby emerged as a key regulator of cancer growth pathways. Although lowering of insulin levels with diet or drugs such as metformin and diazoxide seems generally beneficial, some practitioners also utilize strategic elevations of insulin levels in combination with chemotherapeutic drugs. This indicates a broad spectrum of possibilities for modulating the insulin/IGF-1 system in cancer treatment. With a specific focus on dietary restriction, insulin administration and the insulin-lowering drug diazoxide, such modifications of the insulin/IGF-1 system are the topic of this review. Although preclinical data are promising, we point out that insulin regulation and the metabolic response to a certain diet often differ between mice and humans. Thus, the need for collecting more human data has to be emphasized. PMID- 26878392 TI - The role of mental health and self-efficacy in the pain experience of patients with amyotrophic lateral sclerosis. AB - Complex interactions between pain, depression, and anxiety impact quality of life in patients with ALS. Psychological approaches to pain control may be useful. This study explored the role of self-efficacy in mitigating pain. Individuals registered with the Agency for Toxic Substances and Disease Registry National ALS Registry and who experienced pain were invited to participate in an online survey. Subjects completed the Brief Pain Inventory-Short Form, Hospital Anxiety and Depression Scale, and Chronic Pain Self-Efficacy Scale. Correlations between variables were determined. Multiple linear regression models assessed relationships between depression, anxiety and self-efficacy predictions, and pain severity, interference, and relief. Results recorded that there were 197 participants (58% males, mean age 59 +/- 10 years). Cases or borderline cases of depression or anxiety were common. Mean levels of pain were moderate. Higher pain self-efficacy scores predicted lower pain severity, lower pain interference, and higher pain relief with treatment. As depression scores increased, pain interference with daily life was higher. In conclusion, anxiety and depression are common in patients with ALS and pain. Self-efficacy appears to mitigate pain. A multifactorial approach to pain management should be considered in these patients, addressing mental health and self-efficacy to augment pharmacologic pain treatments. PMID- 26878390 TI - Gain of function of mutant p53: R282W on the peak? AB - Mutant p53 proteins commonly lose their tumor suppression function and gain novel oncogenic functions (gain of function (GOF)). Different p53 mutations are often considered in one class in biological and clinical studies. However, recent studies have revealed that p53 mutations are biologically and clinically distinct. The R282W mutant associates with earlier onset of familial cancers and poorer outcome of cancer patients, suggesting a more prominent GOF effect of this specific mutant. Here we discuss our current understanding on the multifaceted effects of R282W mutation, including its structural features, signaling pathways and clinical implications. The destabilizing nature, aggregation proneness, altered transcriptome and interactome may collaboratively contribute to the unique phenotype of R282W mutation. The quest for mechanistic insights into the unique GOF effects of R282W mutation would further our understanding of the biology of mutant proteins in cancers, and enforce the development of more effective targeted therapies. PMID- 26878391 TI - MiR-125a promotes paclitaxel sensitivity in cervical cancer through altering STAT3 expression. AB - Cervical cancer (CC) is one of the most common malignancies in women. Paclitaxel is the front-line chemotherapeutic agent for treating CC. However, its therapeutic efficacy is limited because of chemoresistance, the mechanism of which remains poorly understood. Here, we used microRNA (miRNA) arrays to compare miRNA expression levels in the CC cell lines, HeLa and CaSki, with their paclitaxel resistance counterparts, HeLa/PR and CaSki/PR. We demonstrate that miR 125a was one of most significantly downregulated miRNAs in paclitaxel-resistant cells, which also acquired cisplatin resistance. And that the upregulation of miR 125a sensitized HeLa/PR and CaSki/PR cells to paclitaxel both in vitro and in vivo and to cisplatin in vitro. Moreover, we determined that miR-125a increased paclitaxel and cisplatin sensitivity by downregulating STAT3. MiR-125a enhanced paclitaxel and cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Clinically, miR-125a expression was associated with an increased responsiveness to paclitaxel combined with cisplatin and a more favorable outcome. These data indicate that miR-125a may be a useful method to enable treatment of chemoresistant CC and may also provide a biomarker for predicting paclitaxel and cisplatin responsiveness in CC. PMID- 26878389 TI - Diet-induced alteration of fatty acid synthase in prostate cancer progression. AB - Fatty acid synthase (FASN) is a cytosolic metabolic enzyme that catalyzes de novo fatty acid synthesis. A high-fat diet (HFD) is attributed to prostate cancer (PCa) progression, but the role FASN on HFD-mediated PCa progression remains unclear. We investigated the role of FASN on PCa progression in LNCaP xenograft mice fed with HFD or low-fat diet (LFD), in PCa cells, and in clinical PCa. The HFD promoted tumour growth and FASN expression in the LNCaP xenograft mice. HFD resulted in AKT and extracellular signal-regulated kinase (ERK) activation and 5' adenosine monophosphate-activated protein kinase (AMPK) inactivation. Serum FASN levels were significantly lower in the HFD group (P=0.026) and correlated inversely with tumour volume (P=0.022). Extracellular FASN release was enhanced in the PCa cells with phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) inhibition and AMPK signalling activation. FASN inhibition resulted in decrease of PCa cell proliferation through PI3K/MAPK downregulation and AMPK activation. Furthermore, AMPK activation was associated with FASN downregulation and PI3K/MAPK inactivation. Clinically, high FASN expression was significantly associated with high Gleason scores and advanced pathological T stage. Moreover, FASN expression was markedly decreased in the PCa response to androgen deprivation therapy and chemotherapy. HFD modulates FASN expression, which may be an important mechanism in HFD-associated PCa progression. Furthermore, a critical stimulatory loop exists between FASN and the PI3K/MAPK system, whereas AMPK signalling was associated with suppression. These may offer appropriate targets for chemoprevention and cancer therapy in HFD-induced PCa. PMID- 26878393 TI - Why you need to include human factors in clinical and empirical studies of in vitro point of care devices? Review and future perspectives. AB - Use of in-vitro point of care devices - intended as tests performed out of laboratories and near patient - is increasing in clinical environments. International standards indicate that interaction assessment should not end after the product release, yet human factors methods are frequently not included in clinical and empirical studies of these devices. Whilst the literature confirms some advantages of bed-side tests compared to those in laboratories there is a lack of knowledge of the risks associated with their use. This article provides a review of approaches applied by clinical researchers to model the use of in-vitro testing. Results suggest that only a few studies have explored human factor approaches. Furthermore, when researchers investigated people-device interaction these were predominantly limited to qualitative and not standardised approaches. The methodological failings and limitations of these studies, identified by us, demonstrate the growing need to integrate human factors methods in the medical field. PMID- 26878395 TI - Uterine torsion, a rare cause of acute abdominal pain in the third trimester of pregnancy: A case report. PMID- 26878396 TI - Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension. AB - The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole and the elongation of luminal cavities. The molecular parameters controlling cell polarization have been heavily scrutinized. In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport. However, little is known about the regulation of the shape and the directional development of lumen into tubes. We demonstrate that the spatial scaffolding of cells by ECM can control tube shapes and can direct their elongation. We developed a minimal organ approach comprising of hepatocyte doublets cultured in artificial microniches to precisely control the spatial organization of cellular adhesions in three dimensions. This approach revealed a mechanism by which the spatial repartition of integrin-based adhesion can elicit an anisotropic intercellular mechanical stress guiding the osmotically driven elongation of lumens in the direction of minimal tension. This mechanical guidance accounts for the different morphologies of lumen in various microenvironmental conditions. PMID- 26878398 TI - Cubic liquid crystalline nanoparticles: optimization and evaluation for ocular delivery of tropicamide. AB - The purpose of this study was to investigate the potential of cubic liquid crystalline nanoparticles for ocular delivery of tropicamide. Ultrasound-assisted fragmentation of cubic liquid crystalline bulk phases resulted in cubic liquid crystalline nanoparticles employing Pluronic F127 as dispersant. The effects of process variables such as sonication time, sonication amplitude, sonication depth, and pre-mixing time on particle size and polydispersity index was investigated using central composite design. The morphology of tropicamide-loaded nanoparticles was found to be nearly cubical in shape by transmission electron microscopy observation. Further, small angle X-ray scattering experiment confirmed the presence of D and P phase cubic structures in coexistence. The optimized tropicamide-loaded cubic nanoparticles showed in vitro corneal permeation of tropicamide across isolated porcine cornea comparable to its commercial preparation, Tropicacyl(r). Ocular tolerance was evaluated by Hen's egg-chorioallantoic membrane test and histological studies. The results of in vivo mydriatic response study demonstrated a remarkably higher area under mydriatic response curve (AUC0->1440 min) values of cubic nanoparticles over Tropicacyl(r) indicating better therapeutic value of cubic nanoparticles. Furthermore, tropicamide-loaded cubic nanoparticles exhibited prolonged mydriatic effect on rabbits as compared to commercial conventional aqueous ophthalmic solution. PMID- 26878397 TI - Time trends in axilla management among early breast cancer patients: Persisting major variation in clinical practice across European centers. AB - Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79-96% and 49 92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary. PMID- 26878399 TI - The Effect of Nasal Septal Perforation and its Treatment on Objective Sleep and Breathing Parameters. AB - BACKGROUND Nasal septal perforation (NSP) may alter nasal airflow patterns and physiology. To the best of our knowledge, no studies in the English literature have investigated the effect of NSP and its treatment on polysomnographic parameters. In this study, we aimed to investigate polysomnographic parameters in patients with NSP as well as changes in those parameters after treatment of NSP. MATERIAL AND METHODS Nineteen patients diagnosed with NSP were included in the study. All patients had baseline and post-procedure polysomnographies (PSG) after insertion of silicone septal button for closure of NSP. RESULTS Both median AHI [5.30 (14.40) vs. 2.40 (14.50)] and median supine AHI [10.00 (42.10) vs. 6.60 (37.00)] decreased after correction of the perforation. There was a large reduction in median supine AHI in patients with a perforation size >66 mm2 [10.10 (34.15) vs. 1.60 (28.30)]. CONCLUSIONS We conclude that NSP did not cause any deterioration in objective sleep parameters as determined by PSG, other than a decrease in REM sleep duration and an increase in supine AHI. Correction of NSP did not affect REM duration and supine AHI decreased after treatment. PMID- 26878400 TI - Open retropubic colposuspension for urinary incontinence in women. AB - BACKGROUND: Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure to correct stress urinary incontinence. OBJECTIVES: The review aimed to determine the effects of open retropubic colposuspension for the treatment of urinary incontinence in women. A secondary aim was to assess the safety of open retropubic colposuspension in terms of adverse events caused by the procedure. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE in process, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 5 May 2015), and the reference lists of relevant articles. We contacted investigators to locate extra studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed urinary incontinence that included open retropubic colposuspension surgery in at least one trial group. DATA COLLECTION AND ANALYSIS: Studies were evaluated for methodological quality or susceptibility to bias and appropriateness for inclusion and data extracted by two of the review authors. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: This review included 55 trials involving a total of 5417 women.Overall cure rates were 68.9% to 88.0% for open retropubic colposuspension. Two small studies suggested lower incontinence rates after open retropubic colposuspension compared with conservative treatment. Similarly, one trial suggested lower incontinence rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower incontinence rate after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (risk ratio (RR) for incontinence 0.46; 95% CI 0.30 to 0.72 before the first year, RR 0.37; 95% CI 0.27 to 0.51 at one to five years, RR 0.49; 95% CI 0.32 to 0.75 in periods beyond five years).Evidence from 22 trials in comparison with suburethral slings (traditional slings or trans-vaginal tape or transobturator tape) found no overall significant difference in incontinence rates in all time periods evaluated (as assessed subjectively RR 0.90; 95% CI 0.69 to 1.18, within one year of treatment, RR 1.18; 95%CI 1.01 to 1.39 between one and five years, RR 1.11; 95% CI 0.97 to 1.27 at five years and more, and as assessed objectively RR 1.24; 95% CI 0.93 to 1.67 within one year of treatment, RR 1.12; 95% CI 0.82 to 1.54 for one to five years follow up, RR 0.70; 95% CI 0.30 to 1.64 at more than five years). However, subgroup analysis of studies comparing traditional slings and open colposuspension showed better effectiveness with traditional slings in the medium and long term (RR 1.35; 95% CI 1.11 to 1.64 from one to five years follow up, RR 1.19; 95% CI 1.03 to 1.37).In comparison with needle suspension, there was a lower incontinence rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42 to 1.03), after the first year (RR 0.56; 95% CI 0.39 to 0.81), and beyond five years (RR 0.32; 95% CI 15 to 0.71).Patient-reported incontinence rates at short, medium and long-term follow-up showed no significant differences between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials incontinence was less common after the Burch (RR 0.38; 95% CI 0.18 to 0.76) than after the Marshall Marchetti Krantz procedure at one to five year follow-up. There were few data at any other follow up times.In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. Voiding problems are also more common after sling procedures compared to open colposuspension. AUTHORS' CONCLUSIONS: Open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85% to 90%. After five years, approximately 70% of women can expect to be dry. Newer minimal access sling procedures look promising in comparison with open colposuspension but their long-term performance is limited and closer monitoring of their adverse event profile must be carried out. Open colposuspension is associated with a higher risk of pelvic organ prolapse compared to sling operations and anterior colporrhaphy, but with a lower risk of voiding dysfunction compared to traditional sling surgery. Laparoscopic colposuspension should allow speedier recovery but its relative safety and long-term effectiveness is not yet known. PMID- 26878401 TI - Vasopressors for hypotensive shock. AB - BACKGROUND: Initial goal-directed resuscitation for hypotensive shock usually includes administration of intravenous fluids, followed by initiation of vasopressors. Despite obvious immediate effects of vasopressors on haemodynamics, their effect on patient-relevant outcomes remains controversial. This review was published originally in 2004 and was updated in 2011 and again in 2016. OBJECTIVES: Our objective was to compare the effect of one vasopressor regimen (vasopressor alone, or in combination) versus another vasopressor regimen on mortality in critically ill participants with shock. We further aimed to investigate effects on other patient-relevant outcomes and to assess the influence of bias on the robustness of our effect estimates. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015 Issue 6), MEDLINE, EMBASE, PASCAL BioMed, CINAHL, BIOSIS and PsycINFO (from inception to June 2015). We performed the original search in November 2003. We also asked experts in the field and searched meta-registries to identify ongoing trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing various vasopressor regimens for hypotensive shock. DATA COLLECTION AND ANALYSIS: Two review authors abstracted data independently. They discussed disagreements between them and resolved differences by consulting with a third review author. We used a random-effects model to combine quantitative data. MAIN RESULTS: We identified 28 RCTs (3497 participants) with 1773 mortality outcomes. Six different vasopressors, given alone or in combination, were studied in 12 different comparisons.All 28 studies reported mortality outcomes; 12 studies reported length of stay. Investigators reported other morbidity outcomes in a variable and heterogeneous way. No data were available on quality of life nor on anxiety and depression outcomes. We classified 11 studies as having low risk of bias for the primary outcome of mortality; only four studies fulfilled all trial quality criteria.In summary, researchers reported no differences in total mortality in any comparisons of different vasopressors or combinations in any of the pre-defined analyses (evidence quality ranging from high to very low). More arrhythmias were observed in participants treated with dopamine than in those treated with norepinephrine (high-quality evidence). These findings were consistent among the few large studies and among studies with different levels of within-study bias risk. AUTHORS' CONCLUSIONS: We found no evidence of substantial differences in total mortality between several vasopressors. Dopamine increases the risk of arrhythmia compared with norepinephrine and might increase mortality. Otherwise, evidence of any other differences between any of the six vasopressors examined is insufficient. We identified low risk of bias and high-quality evidence for the comparison of norepinephrine versus dopamine and moderate to very low-quality evidence for all other comparisons, mainly because single comparisons occasionally were based on only a few participants. Increasing evidence indicates that the treatment goals most often employed are of limited clinical value. Our findings suggest that major changes in clinical practice are not needed, but that selection of vasopressors could be better individualised and could be based on clinical variables reflecting hypoperfusion. PMID- 26878402 TI - Effect of Alkyl Group on MxOy(-) + ROH (M = Mo, W; R = Me, Et) Reaction Rates. AB - A systematic comparison of MxOy(-) + ROH (M = Mo vs W; R = Me vs Et) reaction rate coefficients and product distributions combined with results of calculations on weakly bound MxOy(-).ROH complexes suggest that the overall reaction mechanism has three distinct steps, consistent with recently reported results on analogous MxOy(-) + H2O reactivity studies. MxOy(-) + ROH -> MxOy+1(-) + RH oxidation reactions are observed for the least oxidized clusters, and MxOy(-) + ROH -> MxOyROH(-) addition reactions are observed for clusters in intermediate oxidation states, as observed previously in MxOy(-) + H2O reactions. The first step is weakly bound complex formation, the rate of which is governed by the relative stability of the MxOy(-).ROH charge-dipole complexes and the Lewis acid-base complexes. Calculations predict that MoxOy(-) clusters form more stable Lewis acid-base complexes than WxOy(-), and the stability of EtOH complexes is enhanced relative to MeOH. Consistent with this result, MoxOy(-) + ROH rate coefficients are higher than analogous WxOy(-) clusters. Rate coefficients range from 2.7 * 10(-13) cm(3) s(-1) for W3O8(-) + MeOH to 3.4 * 10(-11) cm(3) s(-1) for Mo2O4(-) + EtOH. Second, a covalently bound complex is formed, and anion photoelectron spectra of the several MxOyROH(-) addition products observed are consistent with hydroxyl-alkoxy structures that are formed readily from the Lewis acid-base complexes. Calculations indicate that addition products are trapped intermediates in the MxOy(-) + ROH -> MxOy+1(-) + RH reaction, and the third step is rearrangement of the hydroxyl group to a metal hydride group to facilitate RH release. Trapped intermediates are more prevalent in MoxOy(-) reaction product distributions, indicating that the rate of this step is higher for WxOy+1RH(-) than for MoxOy+1RH(-). This result is consistent with previous computational studies on analogous MxOy(-) + H2O reactions predicting that barriers along the pathway in the rearrangement step are higher for MoxOy(-) reactions than for WxOy(-). PMID- 26878403 TI - A perfect storm for the NHS? PMID- 26878404 TI - Evaluating the role of the MS specialist nurse. PMID- 26878405 TI - Blood transfusion: patient identification and empowerment. AB - Positive patient identification is pivotal to several steps of the transfusion process; it is integral to ensuring that the correct blood is given to the correct patient. If patient misidentification occurs, this has potentially fatal consequences for patients. Historically patient involvement in healthcare has focused on clinical decision making, where the patient, having been provided with medical information, is encouraged to become involved in the decisions related to their individualised treatment. This article explores the aspects of patient contribution to patient safety relating to positive patient identification in transfusion. When involving patients in their care, however, clinicians must recognise the diversity of patients and the capacity of the patient to be involved. It must not be assumed that all patients will be willing or indeed able to participate. Additionally, clinicians' attitudes to patient involvement in patient safety can determine whether cultural change is successful. PMID- 26878406 TI - Palliative care for advanced dementia in Japan: knowledge and attitudes. AB - This study examined factors contributing to the knowledge and attitudes of nursing home staff regarding palliative care for advanced dementia in Japan. A cross-sectional survey of 275 nurses and other care workers from 74 long-term care facilities was conducted across three prefectures in August 2014. The Japanese versions of the Questionnaire on Palliative Care for Advanced Dementia (qPAD) and Frommelt Attitudes Toward Care of the Dying scale, Form B (FATCOD-B-J) were used. Greater knowledge was exhibited among nursing home staff in facilities that established a manual for end-of-life care. Higher levels of positive attitudes were observed among nursing home staff in facilities that had established a manual and those in facilities with a physician's written opinions on end-of-life care. An organisational effort should be explored to establish end of-life care policies among nursing home staff for advanced dementia. PMID- 26878407 TI - Efficacy of the nurse ethicist in reducing moral distress: what can the NHS learn from the USA? Part 2. AB - In the second of two interrelated articles exploring the concept of moral distress, this article will discuss the efficacy of the nurse ethicist in reducing moral distress. The author will draw on the current literature and on her experiences while in the USA to discuss the ways in which moral distress is being addressed at the team/unit and institutional/organisational levels. It is argued that the nature of moral distress in the UK should be explored further, and that many of the tools used to mitigate moral distress in the USA, such as clinical ethics committees and healthcare ethics consultants, could be adopted more widely in the UK, both to reduce moral distress and to foster more ethical healthcare institutions. The role of the nurse ethicist could be pivotal in bridging the gap between organisational ethics and the individual moral values of bedside nurses. Ultimately, this article argues, the role of the nurse ethicist is worthy of replication in a UK context. PMID- 26878408 TI - A non-comparative evaluation of a chitosan gelling fibre. AB - An evaluation of chitosan gelling fibre dressing (KytoCel, Aspen Medical) was undertaken by tissue viability nurses in a large acute trust from December 2014- May 2015. The aim of this evaluation was to examine whether the gelling-fibre dressing can improve healing outcomes--reduction of bioburden and promotion of wound healing in both acute and chronic wounds that are infected or critically colonised. A total of 20 patients were recruited with acute and other complex wounds where wound infection was already established, or an excessive wound bioburden was delaying healing. Wound swabs were taken before and after dressing application between days 1, 3, 5 and 11 when clinically indicated, or at the surgical and medical teams' request. No more than two sets of swabs were taken in all patients. The evaluation incorporated three main criteria: patient baseline data, dressing performance, and patient perspective. Key findings were a significant reduction in wound size; rapid improvement of the quality of granulation tissue in 11 patients (55%), the reduction of the wound bioburden, and malodour combined with effective exudate management. The investigators also wanted to establish if there was a significant reduction in the identified bacteria from the initial wound swab results. Some patients were on systemic antibiotic therapy, their reduction in bacteria species may also be related to secondary dressings used. More robust investigation may be required to establish if the bacterial reduction was a result of the primary dressing. PMID- 26878409 TI - Vascular access in neonatal care settings: selecting the appropriate device. AB - The aim of this article is to increase knowledge and understanding of issues relating to choosing and using vascular access devices in the neonatal patient population. The article reviews the range of options for acquiring peripheral and central circulatory access in the newborn and considers issues around the choice, insertion, use and aftercare of these medical devices. The issues explored highlight the importance of appropriate device and insertion-site selection, skin preparation and aftercare. Paying due attention to these aspects is an essential component of the neonatal nurses role and ensures that the risks of adverse events are minimised. PMID- 26878410 TI - From staff nurse to nurse consultant. Part 9: writing for publication using client case studies. AB - John Fowler, independent education consultant, continues his series for clinical nurses hoping to share their experiences with a wider audience, with advice on developing a potential article for a professional journal. PMID- 26878411 TI - Can a nursing associate role fill the void left by enrolled nurse training? AB - Emeritus Professor Alan Glasper, University of Southampton, discusses a recent government commitment to formally introduce a nursing associate to the healthcare workforce. PMID- 26878412 TI - Court holds that patient in intensive care unit was not deprived of her liberty. AB - Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses the difficult issue of deprivation of liberty when somebody lacks the capacity to make decisions about their own treatment. PMID- 26878413 TI - Safety standards for invasive procedures and use of anaesthesia. AB - John Tingle discusses two reports that look at safety where invasive procedures are performed in operating theatres and other procedural areas elsewhere. PMID- 26878414 TI - The inconvenient truth: too few nurses. AB - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, considers the bewildering lack of joined-up thinking over nurse recruitment-and its implications for frontline care in the NHS. PMID- 26878415 TI - Color tunable electroluminescence and resistance switching from a ZnO-nanorod TaOx-p-GaN heterojunction. AB - Well-aligned ZnO nanorods have been prepared on p-GaN-sapphire using a vapor phase transport (VPT) technique. A thin sputtered layer of TaOx is employed as the intermediate layer and an n-ZnO-TaOx-p-GaN heterojunction device has been achieved. The current transport of the heterojunction exhibited a typical resistance switching behavior, which originated from the filament forming and breaking in the TaOx layer. Color controllable electroluminescence (EL) was observed from the biased heterojunction at room temperature. Bluish-white wide band emission is achieved from the forward biased device in both the high resistance and low resistance states, while red emission can only be observed for the reverse biased device in the low resistance state. The correlation between the EL and resistance switching has been analyzed in-depth based on the interface band diagram of the heterojunction. PMID- 26878416 TI - Determinants of participation in family and recreational activities of young children with cerebral palsy. AB - PURPOSE: To test a model of child, family and service determinants of participation in family and recreational activities for young children with cerebral palsy (CP). METHODS: Participants were a convenience sample of 429 children (242 males) with CP, aged 18 to 60 months, representing all levels of the Gross Motor Function Classification System (GMFCS). Children were divided into two groups by GMFCS levels, levels I to II and levels III to V. Data on impairments and gross motor function were collected by therapists; parents provided information about children's health conditions and adaptive behaviour. Seven months later, parents reported on family life and services received. One year after the beginning of the study, parents reported their children's participation. Data from the two groups of children were analysed separately using structural equation modelling. RESULTS: The model explained 35% and 40% of the variance of frequency of participation in family and recreation and 28% and 38% of enjoyment in participation, for the two groups of children, respectively. Children's adaptive behaviour, family ecology, and number of community recreational programs were associated with the frequency of participation for both groups. Gross motor function was only associated with the frequency of participation for children in levels III-V. Adaptive behaviour was associated with enjoyment for both groups. The extent services met children's needs was associated with enjoyment for children in levels I to II and family ecology was a determinant of enjoyment for children in levels III to V. CONCLUSION: Supporting children's adaptive behaviour, family ecology, and access to community recreational programmes may foster participation in family and recreational activities for young children with CP. Implications for Rehabilitation Participation in family and recreational activities for young children with CP is complex and influenced by child, family and environmental factors. Practitioners are encouraged to support children's adaptive behaviour and access to community programs and family relationships, involvement in community activities and expectations of their children. Optimizing gross motor function for children who have limitations in self-mobility may enhance their participation in family and recreational activities. For children with a good prognosis for walking, providing services perceived by parents to meet their children's needs may enhance children's enjoyment of participation. PMID- 26878417 TI - Evaluation of inter-observer agreement when using a clinical respiratory scoring system in pre-weaned dairy calves. AB - AIM: To determine inter-observer agreement for a clinical scoring system for the detection of bovine respiratory disease complex in calves, and the impact of classification of calves as sick or healthy based on different cut-off values. METHODS: Two third-year veterinary students (Observer 1 and 2) and one post graduate student (Observer 3) received 4 hours of training on scoring dairy calves for signs of respiratory disease, including rectal temperature, cough, eye and nasal discharge, and ear position. Observers 1 and 2 scored 40 pre-weaning dairy calves 24 hours apart (80 observations) over three visits to a calf-rearing facility, and Observers 1, 2 and 3 scored 20 calves on one visit. Inter-observer agreement was assessed using percentage of agreement (PA) and Kappa statistics for individual clinical signs, comparing Observers 1 and 2. Agreement between the three observers for total clinical score was assessed using cut-off values of >=4, >=5 and >=6 to indicate unhealthy calves. RESULTS: Inter-observer PA for rectal temperature was 0.68, for cough 0.78, for nasal discharge 0.62, for eye discharge 0.63, and for ear position 0.85. Kappa values for all clinical signs indicated slight to fair agreement (<0.4), except temperature that had moderate agreement (0.6). The Fleiss' Kappa for total score, using cut-offs of >=4, >=5 and >=6 to indicate unhealthy calves, was 0.35, 0.06 and 0.13, respectively, indicating slight to fair agreement. CONCLUSIONS AND CLINICAL RELEVANCE: There was important inter-observer discrepancies in scoring clinical signs of respiratory disease, using relatively inexperienced observers. These disagreements may ultimately mean increased false negative or false positive diagnoses and incorrect treatment of cases. Visual assessment of clinical signs associated with bovine respiratory disease needs to be thoroughly validated when disease monitoring is based on the use of a clinical scoring system. PMID- 26878418 TI - Self-Partitioned Droplet Array on Laser-Patterned Superhydrophilic Glass Surface for Wall-less Cell Arrays. AB - In this work, we report a novel method for the creation of superhydrophilic patterns on the surface of hydrophobically coated glass through CO2 laser cleaning. This mask-free approach requires no photolithography for the print of the features, and only a single-step surface pretreatment is needed. The laser cleaned glass surface enables self-partitioning of liquid into droplet arrays with controllable, quantitative volumes. We further designed wall-less cell arrays for the mapping of culturing conditions and demonstrated the potential of this droplet-arraying method. PMID- 26878420 TI - Recovering the triple coincidence of non-pure positron emitters in preclinical PET. AB - Non-pure positron emitters, with their long half-lives, allow for the tracing of slow biochemical processes which cannot be adequately examined by the commonly used short-lived positron emitters. Most of these isotopes emit high-energy cascade gamma rays in addition to positron decay that can be detected and create a triple coincidence with annihilation photons. Triple coincidence is discarded in most scanners, however, the majority of the triple coincidence contains true photon pairs that can be recovered. In this study, we propose a strategy for recovering triple coincidence events to raise the sensitivity of PET imaging for non-pure positron emitters. To identify the true line of response (LOR) from a triple coincidence, a framework utilizing geometrical, energy and temporal information is proposed. The geometrical criterion is based on the assumption that the LOR with the largest radial offset among the three sub pairs of triple coincidences is least likely to be a true LOR. Then, a confidence time window is used to test the valid LOR among those within triple coincidence. Finally, a likelihood ratio discriminant rule based on the energy probability density distribution of cascade and annihilation gammas is established to identify the true LOR. An Inveon preclinical PET scanner was modeled with GATE (GEANT4 application for tomographic emission) Monte Carlo software. We evaluated the performance of the proposed method in terms of identification fraction, noise equivalent count rates (NECR), and image quality on various phantoms. With the inclusion of triple coincidence events using the proposed method, the NECR was found to increase from 11% to 26% and 19% to 29% for I-124 and Br-76, respectively, when 7.4-185 MBq of activity was used. Compared to the reconstructed images using double coincidence, this technique increased the SNR by 5.1-7.3% for I-124 and 9.3-10.3% for Br-76 within the activity range of 9.25 74 MBq, without compromising the spatial resolution or contrast. We conclude that the proposed method can improve the counting statistics of PET imaging for non pure positron emitters and is ready to be implemented on current PET systems. PMID- 26878419 TI - Suppression of mTOR Signaling Pathways in Skeletal Muscle of Finishing Pigs by Increasing the Ratios of Ether Extract and Neutral Detergent Fiber at the Expense of Starch in Iso-energetic Diets. AB - Three iso-energetic and iso-nitrogenous diets were fed to finishing pigs for 28 days to investigate the mammalian target of rapamycin (mTOR) and ubiquitin proteasome signaling pathways of skeletal muscle by altering compositions of dietary energy sources. Diet A, diet B, and diet C contained 44.1%, 37.6%, and 30.9% starch; 5.9%, 9.5%, and 14.3% ether extract (EE); and 12.6%, 15.4%, and 17.8% neutral detergent fiber (NDF), respectively. An increase of mRNA expression of MuRF1 (1.09 +/- 0.10 vs 1.00 +/- 0.08) and MAFbx (1.10 +/- 0.06 vs 1.00 +/- 0.11) and a decrease of concentrations of plasma insulin (8.2 +/- 0.8 vs 10.8 +/- 1.2) and glucose (5.76 +/- 0.12 vs 6.43 +/- 0.33) together with mRNA expression of IRS (0.78 +/- 0.19 vs 1.01 +/- 0.05) and Akt (0.92 +/- 0.01 vs 1.00 +/- 0.05) were observed in pigs fed diet C compared with diet A. Protein levels of total and phosphorylated mTOR (0.31 +/- 0.04 vs 0.48 +/- 0.03 and 0.39 +/- 0.01 vs 0.56 +/- 0.02), 4EBP1 (0.66 +/- 0.06 vs 0.90 +/- 0.09 and 0.60 +/- 0.12 vs 0.84 +/- 0.09), and S6K1 (0.66 +/- 0.01 vs 0.89 +/- 0.01 and 0.48 +/- 0.03 vs 0.79 +/- 0.02) were decreased; however, total and phosphorylated AMPK (0.96 +/- 0.06 vs 0.64 +/- 0.04 and 0.97 +/- 0.09 vs 0.61 +/- 0.09) were increased in pigs fed diet C compared with diet A. In conclusion, diet C suppressed the mTOR pathway and accelerated the ubiquitin-proteasome pathway in skeletal muscle of finishing pigs. PMID- 26878421 TI - Inactivation of Salmonella in Shell Eggs by Hot Water Immersion and Its Effect on Quality. AB - Thermal inactivation kinetics of heat resistant strains of Salmonella Enteritidis in shell eggs processed by hot water immersion were determined and the effects of the processing on egg quality were evaluated. Shell eggs were inoculated with a composite of heat resistant Salmonella Enteritidis (SE) strains PT8 C405, 2 (FSIS #OB030832), and 6 (FSIS #OB040159). Eggs were immersed in a circulating hot water bath for various times and temperatures. Come-up time of the coldest location within the egg was 21 min. SE was reduced by 4.5 log at both hot water immersion treatments of 56.7 C for 60 min and 55.6 degrees C for 100 min. Decimal reduction times (D-values) at 54.4, 55.6, and 56.7 degrees C were 51.8, 14.6, and 9.33 min, respectively. The z-value was 3.07 degrees C. Following treatments that resulted in a 4.5 log reduction (56.7 degrees C/60 min and 55.6 degrees C/100 min), the surviving population of SE remained static during 4 wk of refrigerated storage. After processing under conditions resulting in 4.5 log reductions, the Haugh unit and albumen height significantly increased (P < 0.01) and yolk index significantly decreased (P < 0.05). The shell dynamic stiffness significantly increased (P < 0.05), while static compression shell strength showed no significant difference (P < 0.05). Vitelline membrane strength significantly increased (P < 0.05); although, no significant difference (P < 0.05) was observed in vitelline membrane elasticity. In summary, the hot water immersion process inactivated heat resistant SE in shell eggs by 4.5 log, but also significantly affected several egg quality characteristics. PMID- 26878423 TI - Toward the Synthesis of Sub-15 nm Ag Nanocubes with Sharp Corners and Edges: The Roles of Heterogeneous Nucleation and Surface Capping. AB - We report a polyol method for the facile synthesis of Ag nanocubes having sharp corners and edges, together with edge lengths below 15 nm. The rapid nucleation of Ag atoms was facilitated through the addition of a trace amount of SH(-) to generate Ag2S clusters while the corners and edges of the nanocubes were sharpened through the introduction of Br(-) as a regulator of the growth kinetics and a capping agent for the Ag(100) surface. Because of their much smaller size relative to the more commonly used capping agent based on poly(vinylpyrrolidone), Br(-) ions are more effective in passivating the {100} facets on very small Ag nanocubes. The mechanistic roles of these additives, along with the effects of their interactions with other species present in the reaction solution, were all systematically investigated. The concentration of SH(-) was found to be a particularly effective parameter for tuning the edge length of the nanocubes. As a result of the understanding gained during the course of this study, Ag nanocubes with uniform edge lengths controllable in the range of 13-23 nm could be reliably produced. The nanocubes of 13.4 +/- 0.4 nm in edge length constitute the smallest nanocrystals of this kind reported to date; they also possess sharper corners and edges relative to the limited examples of sub-20 nm Ag nanocubes reported in the literature. The availability of such small and sharp Ag nanocubes will open the door to an array of applications in plasmonics, catalysis, and biomedicine. PMID- 26878425 TI - [A New Nomenclature for Functional Disorders is on Demand]. PMID- 26878426 TI - [First Aid with Stroke]. PMID- 26878422 TI - PREPULSE INHIBITION DEFICITS ONLY IN FEMALES WITH OBSESSIVE-COMPULSIVE DISORDER. AB - BACKGROUND: Deficits in sensorimotor gating have been hypothesized to underlie the inability to inhibit repetitive thoughts and behaviors. To test this hypothesis, this study assessed prepulse inhibition (PPI), a measure of sensorimotor gating, across three psychiatric disorders (obsessive-compulsive disorder [OCD], social anxiety disorder [SAD], and anorexia nervosa [AN]) whose clinical presentations include repetitive thoughts and behaviors METHODS: We tested acoustic PPI in unmedicated individuals with OCD (n = 45), SAD (n = 37), and AN (n = 26), and compared their results to matched healthy volunteers (n = 62). All participants completed a structured clinical interview and a clinical assessment of psychiatric symptom severity. RESULTS: Percent PPI was significantly diminished in females with OCD compared to healthy female volunteers (P = .039). No other differences between healthy volunteers and participants with disorders (male or female) were observed. Percent PPI was not correlated with severity of obsessions and compulsions, as measured by the Yale Brown Obsessive Compulsive Scale. CONCLUSIONS: This is the first study to assess PPI in participants with SAD or AN, and the largest study to assess PPI in participants with OCD. We found PPI deficits only in females with OCD, which suggests that the cortico-striato-pallido-thalamic and pontine circuitry (believed to underlie PPI) differs between males and females with OCD. Given that PPI deficits were only present in females with OCD and not related to repetitive thoughts and behaviors, our results do not support the hypothesis that sensorimotor gating deficits, as measured by PPI, underlie the inability to inhibit repetitive thoughts and behaviors in individuals with OCD, SAD, and AN. PMID- 26878424 TI - Murine Sertoli cells promote the development of tolerogenic dendritic cells: a pivotal role of galectin-1. AB - Sertoli cells (SCs) possess inherent immunosuppressive properties and are major contributors to the immunoprivileged status of mammalian testis. SCs have been reported to inhibit the activation of B cells, T cells and natural killer cells but not dendritic cells (DCs). Herein, we present evidence that co-culture with SCs results in a persistent state of DC immaturity characterized by down regulation of the surface molecules I-A/E, CD80, CD83, CD86, CCR7 and CD11c, as well as reduced production of pro-inflammatory cytokines. SC-conditioned DCs (SC DCs) displayed low immunogenicity and enhanced immunoregulatory functions, including the inhibition of T-cell proliferation and the promotion of Foxp3(+) regulatory T-cell development. Mechanistically, the activation of p38, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was suppressed in SC-DCs. More importantly, we demonstrate that galectin-1 secreted by SCs plays a pivotal role in the differentiation of functionally tolerogenic SC-DCs. These findings further support the role of SCs in maintaining the immunoprivileged environment of the testis and provide a novel approach to derive tolerogenic DCs, which may lead to alternative therapeutic strategies for the treatment of immunopathogenic diseases. PMID- 26878427 TI - [Management of acute ischemic stroke]. PMID- 26878428 TI - [Man at the Frontier of his Being: Scope of the Concept of "Limit Situation" in Psychiatry and Psychotherapy Following Jaspers' Existential Ontology]. AB - BACKGROUND: The existential concept of "limit situation" was proposed by Jaspers as the inevitable threshold of human beings at their ordinary mode of being, namely Dasein, which has to be crossed to reach Existence as the proper mode of being after having transcended an existential challenge. A failure at facing limit situations indicates that they are ineluctable and have to be assumed. METHOD: The starting point is the analysis of Jaspers' concept of limit situations, both within the antinomic structure of the human condition as well as the duality of being-in-the-world. An attempt is made here to interpret the ontological determination of the limit situation as an ontic one, which could be relevant to psychiatric and psychotherapeutic practice. RESULTS: The distinction between Dasein and Existence as modes of being is at the basis of Jaspers' existential philosophy. Limit situations cannot be veiled; therefore, they require a transcendence movement of the self in order to overcome enclosures and to reach the mode of being of Existence as authentic selfhood. Jaspers creates an ontological typology of limit situations in which suffering plays a key role. An ontic correspondence for psychiatry and psychotherapy refers to the importance of critical life events, of suicidality, of rigid thought styles and behavior patterns as enclosures; illness is both a limit situation in itself and also its consequence. In anthropological terms, the concepts of existential vulnerability and competence in dealing with limit situations have proved to be rewarding. DISCUSSION: The ontic correspondence to Jaspers' ontological concept of limit situations suggested by the author makes a fruitful contribution to psychiatry and psychotherapy, because it draws attention to the person-environment fit as a possible predetermined breaking point that could lead to psychopathologically relevant failure. Critical life events understood as relational, as well as existential vulnerability and defense mechanisms biographically illuminated could contribute to an improvement of competence in dealing with limit situations within the psychotherapeutic practice. PMID- 26878429 TI - [Physician Counseling about Physical and Sports Activity in Neurological Practices in Germany: Results of a Survey Among Members of the German Neurological Society]. AB - Physical inactivity is a major but modifiable risk factor for morbidity and mortality. Regular physical activity has preventive and therapeutic effects on numerous diseases including neurological disorders. Therefore, it is desirable that physicians motivate their patients to increase their physical and sports activities and that they help them to overcome barriers to exercising. The present study is a survey of neurologists who are members of the German Neurological Society with their own practices; they were asked whether they advised their patients on the benefits of physical activity. Details on physician counseling on physical activity were obtained, such as the frequency of counseling, the neurological disorders considered by the practitioners to be worth the effort of counseling, and the barriers to exercise on the part of patients. More than 80 % of the participants who responded to the survey stated that they frequently provide their patients with advice on the preventive and therapeutic aspects of physical activity. Almost all of them recommended endurance sports; this was followed by Far Eastern types of sport such as tai chi or yoga (70 % of all physicians who advice sports activities). The frequency of counseling about physical activity significantly correlated to the physician's own sports activity. Frequency of counseling was reduced if the physician assessed the patients to be incapable of adopting and maintaining a lifestyle of habitual physical activity. Lack of time as well as an insufficient reimbursement of the counseling, however, did not significantly influence the frequency of counseling. The physician's own sports activity matched that of individuals with similar social status. Thus, a selection bias does not seem to be of importance regarding the results of the survey. However, since only 169 of the 784 invited neurologists (21.6 %) responded to the questionnaire, the representativeness of the survey may be limited. Counseling about physical activity seems to be an essential part of consultations in neurological practices. PMID- 26878432 TI - [Home Treatment]. AB - Home Treatment (HT) means acute psychiatric treatment in the patient's usual environment. Conceptually, HT is to be differentiated from other home-based services: It is limited with regard to duration and multiprofessional (e. g. psychiatrist plus psychiatric nursing staff plus social worker); the "24/7" accessibility is frequently provided by the corresponding background hospital infrastructure. Target group are acutely mentally ill persons with an indication to inpatient treatment, who are willing to cooperate, and absence of endangerment to self and others. In contrast to the Scandinavian and many Anglophone countries where nationwide HT services are delivered, there are not many HT sites in Germany so far. Consequently, empirical data concerning HT in Germany is scarce. In summary, international studies show equivalent effects on psychopathological measures compared to inpatient treatment, reductions with regard to inpatient days, higher patient satisfaction and a trend towards cost-effectivity. PMID- 26878433 TI - Maintenance Treatment With Low-Dose Mercaptopurine in Combination With Allopurinol in Children With Acute Lymphoblastic Leukemia and Mercaptopurine Induced Pancreatitis. AB - Mercaptopurine (6-mercaptopurine, 6MP) is a mainstay of curative therapy in childhood acute lymphoblastic leukemia (ALL), and contributes to its 90% overall survival rate. We present two patients with ALL who suffered with severe pancreatitis secondary to 6MP. Through the use of allopurinol in conjunction with reduced dose 6MP, we were able to continue 6MP without further pancreatitis. This report contributes to the small body of literature on 6MP associated pancreatitis in childhood ALL and describes a novel approach to continued use of 6MP during therapy. PMID- 26878434 TI - A simulation study of the energy-efficient options for upgrading and retrofitting a medium-size municipal wastewater treatment plant. AB - Many municipal wastewater treatment plants are retrofitted with membrane filtration that replaces secondary clarification. Such a solution saves space and improves overall treatment efficiency but at the cost of increased energy consumption and reduced potential for energy recovery from sewage sludge. Thus, the plant takes a step back from reaching energy self-sufficiency. In the presented case study, two alternative upgrade options were simulated for a medium size municipal wastewater treatment plant in Poland: the first one assumed optimization of the existing bioreactor, and the other - installation of microfiltration membrane units inside the bioreactor. In both cases, anaerobic digestion of waste sludge with biogas utilization is planned. The results have shown that while under both upgrade options, the plant's capacity can be effectively increased by approximately 50%, their effects on the plant's energy balance will be very different. Although the installation of membrane modules accompanied by the construction of anaerobic digestion tanks improves the plant's energy balance, it will remain negative. The option of optimizing the existing biological treatment system produces a positive energy balance with more energy produced from biogas than consumed. Thus, the plant is able to approach energy self-sufficiency. It has been concluded that retrofitting the plants with membrane filtration is not always the best option from the energy balance point of view and it should be preceded with a detailed analysis on a case-by-case basis. PMID- 26878435 TI - HSO3Cl: a prototype molecule for studying OH-stretching overtone induced photodissociation. AB - Vibrationally induced photodissociation in sulfurochloridic acid (HSO3Cl) is found to be a viable process to form SO3 and HCl from excitations of the OH stretching overtone starting at nuOH = 4. Reactive molecular dynamics simulations on a fully-dimensional potential energy surface fitted to MP2 calculations show that hydrogen transfer and HCl elimination compete with one another on the nanosecond time scale. Excitation with 5 and 6 quanta in the OH-stretch direct elimination of HCl is a dominant process on the several hundred picosecond time scale. At longer times, HCl formation is preceded by intramolecular hydrogen transfer and concomitant excitation of torsional degrees of freedom. As HSO3Cl is a suitable proxy for H2SO4, which is relevant for weather and climate in the upper atmosphere, it is concluded that vibrationally induced photodissociation is a possible mechanism for H2SO4 decomposition. Final state energy distributions for different internal degrees of freedom are predicted which should be observable in laboratory measurements. PMID- 26878437 TI - Strong and Biostable Hyaluronic Acid-Calcium Phosphate Nanocomposite Hydrogel via in Situ Precipitation Process. AB - Hyaluronic acid (HAc) hydrogel exhibits excellent biocompatibility, but it has limited biomedical application due to its poor biomechanical properties as well as too-fast enzymatic degradation. In this study, we have developed an in situ precipitation process for the fabrication of a HAc-calcium phosphate nanocomposite hydrogel, after the formation of the glycidyl methacrylate conjugated HAc (GMHA) hydrogels via photo-cross-linking, to improve the mechanical and biological properties under physiological conditions. In particular, our process facilitates the rapid incorporation of calcium phosphate (CaP) nanoparticles of uniform size and with minimal agglomeration into a polymer matrix, homogeneously. Compared with pure HAc, the nanocomposite hydrogels exhibit improved mechanical behavior. Specifically, the shear modulus is improved by a factor of 4. The biostability of the nanocomposite hydrogel was also significantly improved compared with that of pure HAc hydrogels under both in vitro and in vivo conditions. PMID- 26878438 TI - Disease progression in aggressive periodontitis patients. A Retrospective Study. AB - AIM: The primary aim of this study was to retrospectively ascertain disease progression in a cohort of aggressive periodontitis patients (AgP). MATERIALS AND METHODS: Patients treated at a specialist setting and referred back to general practice for periodontal maintenance were recalled and examined in a single visit. Disease progression during follow-up was assessed and historical data collected from the patient's records. Factors that could potentially influence tooth loss rates at the patient level were explored by linear regression analysis. At the tooth level, chi-square test and OR for tooth loss were calculated. RESULTS: Sixty-six subjects completed the study. The mean follow-up was 6.97 years (95% CI 6.25-7.69). The mean annual tooth loss rate was 0.27 teeth per patient/year (95% CI 0.17-0.36). At the patient level, having received surgical treatment and the performance of interproximal cleaning were found to significantly reduce the annual tooth loss rates. At the tooth level, deep probing depths after treatment were significantly associated with increased tooth loss rates (OR 4.39 for PPD 5-6 mm and OR 11.68 for PPD >6 mm, respectively, compared with PPD <5 mm). CONCLUSIONS: In this sample of patients, the annual tooth loss rates were found to be higher than previously described. PMID- 26878436 TI - Nociceptin Opioid Receptor (NOP) as a Therapeutic Target: Progress in Translation from Preclinical Research to Clinical Utility. AB - In the two decades since the discovery of the nociceptin opioid receptor (NOP) and its ligand, nociceptin/orphaninFQ (N/OFQ), steady progress has been achieved in understanding the pharmacology of this fourth opioid receptor/peptide system, aided by genetic and pharmacologic approaches. This research spawned an explosion of small-molecule NOP receptor ligands from discovery programs in major pharmaceutical companies. NOP agonists have been investigated for their efficacy in preclinical models of anxiety, cough, substance abuse, pain (spinal and peripheral), and urinary incontinence, whereas NOP antagonists have been investigated for treatment of pain, depression, and motor symptoms in Parkinson's disease. Translation of preclinical findings into the clinic is guided by PET and receptor occupancy studies, particularly for NOP antagonists. Recent progress in preclinical NOP research suggests that NOP agonists may have clinical utility for pain treatment and substance abuse pharmacotherapy. This review discusses the progress toward validating the NOP-N/OFQ system as a therapeutic target. PMID- 26878439 TI - Impact of crystalline quality on neuronal affinity of pristine graphene. AB - Due to its outstanding mechanical and electrical properties as well as chemical inertness, graphene has attracted a growing interest in the field of bioelectric interfacing. Herein, we investigate the suitability of pristine, i.e. without a cell adhesive coating, chemical vapor deposition (CVD) grown monolayer graphene to act as a platform for neuronal growth. We study the development of primary hippocampal neurons grown on bare graphene (transferred on glass coverslip) for up to 5 days and show that pristine graphene significantly improves the neurons adhesion and outgrowth at the early stage of culture (1-2 days in vitro). At the later development stage, neurons grown on coating free graphene (untreated with poly-L-lysine) show remarkably well developed neuritic architecture similar to those cultured on conventional poly-L-lysine coated glass coverslips. This exceptional possibility to bypass the adhesive coating allows a direct electrical contact of graphene to the cells and reveals its great potential for chronic medical implants and tissue engineering. Moreover, regarding the controversial results obtained on the neuronal affinity of pristine graphene and its ability to support neuronal growth without the need of polymer or protein coating, we found that the crystallinity of CVD grown graphene plays an important role in neuronal attachment, outgrowth and axonal specification. In particular, we show that the decreasing crystalline quality of graphene tunes the neuronal affinity from highly adhesive to fully repellent. PMID- 26878441 TI - Management of Cytomegalovirus Retinitis in HIV and Non-HIV Patients. AB - As CMVR continues to affect HIV-positive and non-HIV immunosuppressed patients, ophthalmologists must continue to tailor diagnostics and therapeutics to individual cases. In HIV-related disease, ocular fluid sampling and intravitreal drug delivery are considerations, but systemic antiviral therapy is paramount in the initial management from both ophthalmic and systemic morbidity standpoints. Non-HIV-related disease should be approached with a multidisciplinary team, including an ophthalmologist/vitreoretinal/uveitis specialist for consideration of intravitreal antiviral therapy with qualitative and quantitative aqueous PCR monitoring, and consideration of PCR genome sequencing for CMV strains that may become resistant to antiviral therapies from long-term antiviral prophylactic exposure. Hematologists or oncologists may help with patients who remain bone marrow-suppressed following transplantation or systemic chemotherapy. Because of related toxicities of the anti-CMV medications and immunosuppressive medications (eg, bone marrow suppression and cytopenias), infectious disease consultation can help in the treatment and monitoring of side effects. PMID- 26878440 TI - Inhibition of oncogenic BRAF activity by indole-3-carbinol disrupts microphthalmia-associated transcription factor expression and arrests melanoma cell proliferation. AB - Indole-3-carbinol (I3C), an anti-cancer phytochemical derived from cruciferous vegetables, strongly inhibited proliferation and down-regulated protein levels of the melanocyte master regulator micropthalmia-associated transcription factor (MITF-M) in oncogenic BRAF-V600E expressing melanoma cells in culture as well as in vivo in tumor xenografted athymic nude mice. In contrast, wild type BRAF expressing melanoma cells remained relatively insensitive to I3C anti proliferative signaling. In BRAF-V600E-expressing melanoma cells, I3C treatment inhibited phosphorylation of MEK and ERK/MAPK, the down stream effectors of BRAF. The I3C anti-proliferative arrest was concomitant with the down-regulation of MITF-M transcripts and promoter activity, loss of endogenous BRN-2 binding to the MITF-M promoter, and was strongly attenuated by expression of exogenous MITF-M. Importantly, in vitro kinase assays using immunoprecipitated BRAF-V600E and wild type BRAF demonstrated that I3C selectively inhibited the enzymatic activity of the oncogenic BRAF-V600E but not of the wild type protein. In silico modeling predicted an I3C interaction site in the BRAF-V600E protomer distinct from where the clinically used BRAF-V600E inhibitor Vemurafenib binds to BRAF-V600E. Consistent with this prediction, combinations of I3C and Vemurafenib more potently inhibited melanoma cell proliferation and reduced MITF-M levels in BRAF V600E expressing melanoma cells compared to the effects of each compound alone. Thus, our results demonstrate that oncogenic BRAF-V600E is a new cellular target of I3C that implicate this indolecarbinol compound as a potential candidate for novel single or combination therapies for melanoma. (c) 2016 Wiley Periodicals, Inc. PMID- 26878442 TI - Distinguishing Diabetic Macular Edema From Capillary Nonperfusion Using Optical Coherence Tomography Angiography. AB - BACKGROUND AND OBJECTIVE: To describe the appearance of diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and distinguish it from capillary nonperfusion. PATIENTS AND METHODS: Patients with DME were recruited for OCTA imaging. Eyes with confounding retinal diseases were excluded. Using 3 mm * 3 mm OCT angiograms segmented into the superficial and deep inner retinal vascular plexuses, two graders described the appearance of DME and confirmed the diagnosis with structural OCT and fluorescein angiography. RESULTS: DME was evaluated in 17 eyes of 12 patients. The cystoid spaces in DME appeared completely devoid of flow on the OCT angiograms and were oblong in shape with smooth borders that did not follow the distribution of surrounding capillaries, whereas areas of capillary nonperfusion were a greyer hue and had irregular borders. CONCLUSIONS: The cystoid spaces in DME can be differentiated from capillary nonperfusion using OCTA. OCTA may help to guide treatment decisions in the future. PMID- 26878443 TI - Evaluation of Preretinal Neovascularization in Proliferative Diabetic Retinopathy Using Optical Coherence Tomography Angiography. AB - BACKGROUND AND OBJECTIVE: To describe a method for visualizing preretinal neovascularization in proliferative diabetic retinopathy (PDR) using optical coherence tomography angiography (OCTA) and report the findings in the surrounding vasculature. PATIENTS AND METHODS: Patients with PDR diagnosed on clinical examination who received OCTA scans using the RTVue XR Avanti (Optovue, Fremont, CA) were evaluated. To visualize preretinal neovascularization, OCT angiograms were segmented to project vasculature above the internal limiting membrane (ILM). OCT angiograms were segmented between the ILM and Bruch's membrane to show adjacent retinal vasculature. RESULTS: Thirteen eyes were determined to have preretinal neovascularization in the posterior pole based on OCTA. One OCT angiogram was not of sufficient quality and thus was eliminated from further study. Eleven eyes (92%) had neovascularization adjacent to retinal capillary nonperfusion and six (50%) were adjacent to intraretinal microvascular abnormalities (IRMAs). CONCLUSION: OCTA provided high-resolution, depth-resolved blood flow information, allowing for visualization of preretinal neovascularization, IRMA, and adjacent capillary nonperfusion. PMID- 26878444 TI - Analysis of Choroidal and Retinal Vasculature in Inherited Retinal Degenerations Using Optical Coherence Tomography Angiography. AB - BACKGROUND AND OBJECTIVE: To describe the retinal vasculature and choriocapillaris, as well as the transition zone between the diseased and healthy tissue, in eyes with inherited retinal degenerations using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Patients with inherited retinal degenerations were recruited for OCTA imaging. Retinal vasculature was assessed for increased intercapillary space and foveal avascular zone abnormalities. Choriocapillaris, retinal pigment epithelium (RPE), and photoreceptor disruption were noted, and the borders were evaluated to speculate which layers become affected first. RESULTS: Fourteen eyes of seven subjects with inherited retinal degenerations were included. All eyes (100%) demonstrated retinal thinning and increased intercapillary spaces overlying focal outer retinal changes. In all eyes, the region of choriocapillaris changes was smaller than the region of overlying RPE and photoreceptor alteration, suggesting the vascular loss was secondary. CONCLUSION: OCTA is able to provide highly detailed vascular information in eyes with inherited retinal degenerations and may be useful to better understand the pathogenesis of these diseases. PMID- 26878445 TI - Vascularization of Irregular Retinal Pigment Epithelial Detachments in Chronic Central Serous Chorioretinopathy Evaluated With OCT Angiography. AB - BACKGROUND AND OBJECTIVE: To assess eyes with flat, irregular retinal pigment epithelial detachments (RPEDs) associated with central serous chorioretinopathy (CSCR) for choroidal neovascularization (CNV) using optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: Retrospective review of OCTA images of chronic CSCR eyes with irregular RPED (group 1) and regular RPED (controls, group 2) for presence of CNV, subretinal fluid, and intraretinal fluid. Fluorescein angiography was also evaluated for CNV. RESULTS: CNV was detected using OCTA in 13 of 31 eyes (41.9%) in group 1 and in one of 18 eyes (5.6%) in group 2 (P = .007). Irregular RPED was a risk factor for CNV (odds ratio [OR] = 12.28; 95% CI, 1.45-104.3). There was no significant difference between detection by OCTA and FA (P = 1.0). Sensitivity and specificity of detection by OCTA were 85.7% and 95.7%, respectively. CONCLUSIONS: Irregular RPEDs in chronic CSCR eyes may harbor neovascularization more often than previously thought, which has implications on therapy. PMID- 26878446 TI - Imaging of Melanin Disruption in Age-Related Macular Degeneration Using Multispectral Imaging. AB - BACKGROUND AND OBJECTIVE: To investigate whether multispectral imaging (MSI) is able to obtain a noninvasive view of melanin disruption associated with age related macular degeneration (AMD), which could support early diagnosis and potential treatment strategies. PATIENTS AND METHODS: A single retinal center, retrospective, observational, image analysis study of MSI images of 43 patients was done to determine the extent of melanin pigment exhibited in association with AMD, based on the Age-Related Eye Disease Study classification and grading scale. Corresponding fundus photos were also graded for 12 of the eyes. RESULTS: Fifty one of 61 eyes (84%) of 43 patients with AMD were determined to have melanin disruption in their MSI images in at least the central and/or one of four inner ETDRS areas. There was a relationship between severity of disease and the degree of melanin disruption. The sensitivity of fundus photography for melanin pigment as compared to MSI was only 62.5%, with three false-negatives. CONCLUSION: A direct, noninvasive, unobstructed view of melanin disruption associated with AMD can be observed using MSI. PMID- 26878447 TI - The Influence of Age and Central Foveal Thickness on Foveal Zone Size in Healthy People. AB - BACKGROUND AND OBJECTIVE: To investigate the influence of age and central foveal thickness (CFT) on the foveal avascular zone (FAZ) size in healthy people using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: A cross section study. One hundred thirty-two healthy subjects (224 eyes) were included. All participants underwent examination with OCTA. CFT and FAZ size, including vertical radius (VR), horizontal radius (HR), and area, were measured. RESULTS: Linear regression analysis showed a positive correlation between age and FAZ size. The HR, VR, and area had an increase of 0.001 mm (P = .002), 0.001 mm (P = .001), and 0.001 mm(2) (P = .000) each year, respectively. There was a negative correlation between CFT and FAZ size. When the CFT increased per 1 um, the HR, VR, and area decreased by 0.002 mm (P = .000), 0.001 mm (P = .000), and 0.003 mm(2) (P = .000), respectively. CONCLUSIONS: FAZ size increases with age and decreases with CFT. OCTA is a novel method to study the FAZ in healthy people. PMID- 26878448 TI - Intravitreal Diclofenac in the Treatment of Macular Edema Due to Branch Retinal Vein Occlusion. AB - BACKGROUND AND OBJECTIVE: To evaluate the effect of a single dose of intravitreal diclofenac on macular edema (ME) due to branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: In this prospective, interventional case series, 15 eyes with BRVO and ME with central macular thickness (CMT) greater than 250 um on spectral-domain optical coherence tomography (SD-OCT) were enrolled. All patients were given 0.05 mg/0.1 mL of intravitreal diclofenac under aseptic conditions and followed up for 3 months with respect to best-corrected visual acuity (BCVA), intraocular pressure (IOP), fundus fluorescein angiography, and CMT measured on OCT. RESULTS: The mean visual acuity improved from 0.115 +/- 0.03 preoperatively to 0.356 +/- 0.29 at 3 months (P = .002). Mean line improvement was 2.2 +/- 1.6. Mean preoperative CMT decreased from 453.2 um +/- 55.3 um to 340.47 um +/- 101 um at 3 months postoperatively (P = .001). The mean preoperative IOP was 16.4 mm Hg +/- 1.59 mm Hg, whereas the mean postoperative IOP was 16.6 mm Hg +/- 1.58 mm Hg (P = .08). None of the 12 phakic eyes showed evidence of cataract progression. CONCLUSION: Intravitreal diclofenac is safe and effective in improving BCVA and decreasing CMT in patients with BRVO and ME. PMID- 26878449 TI - Post-Marketing Survey of Adverse Events Following Ocriplasmin. AB - BACKGROUND AND OBJECTIVE: To study the post-marketing safety profile of ocriplasmin (Jetrea; ThromboGenics, Iselin, NJ) as experienced by retinal physicians in the United States. STUDY DESIGN/MATERIALS AND METHODS: Two thousand four hundred sixty-five retinal physicians were surveyed regarding their frequency of use of ocriplasmin and reports of ocular adverse events. RESULTS: There were 270 respondents (11%) who reported treating 1,056 eyes with ocriplasmin. The reports of adverse events (AE) were as follows: acute decline in visual acuity (16.95%), development of submacular fluid or serous retinal detachment (10.23%), dyschromatopsia (9.09%), progression of vitreomacular traction to macular hole (8.71%), development of retinal detachment (2.65%), development of retinal tear (1.99%), development of afferent pupillary defect (1.80%), electroretinography abnormalities (0.57%), crystalline lens instability (0.38%), and vasculitis (0.28%). CONCLUSION: Although the frequency of some ocular AEs reported in this study are comparable to those reported in the phase 3 registration trials, additional phase 4 safety studies are warranted to better understand the pathophysiology and clinical relevance of ocular AEs of ocriplasmin. PMID- 26878450 TI - A Biological Tissue Adhesive and Dissolvent System for Intraocular Tumor Plaque Brachytherapy. AB - PURPOSE: To examine a novel technique for simplified placement and removal of plaque brachytherapy by fibrin glue and urokinase (medac Gmbh, Hamburg, Germany). MATERIALS AND METHODS: In six enucleated porcine eyes, plaques were placed on the episclera and fibrin glue was applied to cover it. Urokinase was used to dissolve the glue in three eyes and saline was used in three eyes. Adhesion strength was measured further on 15 plaques affixed to porcine eyes (glued in five with intact conjunctiva, glued in five with removed conjunctiva, and sutured in five). RESULTS: Saline had no effect on the glue-plaque-eye complex, whereas the urokinase (0.38 mL +/- 0.08 mL) easily dissolved the adhesion between the glue layer and surrounding tissues. The weight required to detach the plaques was 0.349 kg +/- 0.173 kg for glued eyes with intact conjunctiva, 0.405 kg +/- 0.083 kg for sutured eyes (P = .59), and 0.032 kg +/- 0.004 kg for glued eyes without intact conjunctiva (P <= .015). CONCLUSIONS: The usage of the biological adhesive and dissolvent system was applicable for plaque surgery in an ex vivo animal model. PMID- 26878451 TI - Implantation of Modular Photovoltaic Subretinal Prosthesis. AB - BACKGROUND AND OBJECTIVE: Establish the surgical procedure for subretinal implantation of multiple photovoltaic arrays for the restoration of sight. MATERIALS AND METHODS: Multiple silicon photovoltaic arrays of 1 mm in diameter and 30 um in thickness were implanted subretinally via single retinotomy in rabbits. Ophthalmoscopic imaging and optical coherence tomography (OCT) were used to validate the implants' placement. RESULTS: Vitrectomy, followed by subretinal fluid injection for retinal detachment and retinotomy, allowed accurate placement of seven modules in the bleb, covering approximately a 3.5-mm diameter area on the retina via a single 1.5-mm retinotomy. OCT confirmed complete reattachment of the retina over the implants. CONCLUSION: Subretinal implantation of multiple photovoltaic arrays via a single retinotomy, followed by their tiling, minimizes the scleral and retinal incisions and provides better fit to the spherical shape of the eye ball, compared to a single, larger module. Such minimally traumatic procedure can be performed with 20-gauge intraocular instruments. PMID- 26878453 TI - Early Swept-Source Optical Coherence Tomography Angiography Findings in Unilateral Acute Idiopathic Maculopathy. AB - Unilateral acute idiopathic maculopathy (UAIM) is a rare disorder presenting in young people with an acute onset of unilateral central visual loss often associated with a prodromal flu-like illness. The authors present the early anatomical findings of a 35-year-old man clinically diagnosed with UAIM using swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography. PMID- 26878452 TI - En Face Optical Coherence Tomography and Optical Coherence Tomography Angiography Imaging of Taxane-Associated Cystoid Macular Edema. AB - The taxanes are chemotherapeutic agents that may, in rare cases, cause cystoid macular edema without leakage on fluorescein angiography. Two patients with evidence of taxane-related macular edema presented and were evaluated using novel en face optical coherence tomography (OCT) and OCT angiography (OCTA) imaging modalities. Although OCTA revealed no flow abnormalities in either patient, en face OCT revealed a striking bilateral symmetric cystic tessellation pattern. PMID- 26878454 TI - Sector Retinitis Pigmentosa Associated With Novel Compound Heterozygous Mutations of CDH23. AB - Usher syndrome is an autosomal recessive condition characterized by retinitis pigmentosa (RP) and congenital hearing loss, with or without vestibular dysfunction. Allelic variants of CDH23 cause both Usher syndrome type 1D (USH1D) and a form of nonsyndromic hearing loss (DFNB12). The authors describe here a 34 year-old patient with congenital hearing loss and a new diagnosis of sector RP who was found to have two novel compound heterozygous mutations in CDH23, including one missense (c.8530C > A; p.Pro2844Thr) and one splice-site (c.5820 + 5G > A) mutation. This is the first report of sector RP associated with these types of mutations in CDH23. PMID- 26878455 TI - Spontaneous Resolution of Large Macular Retinoschisis in Enhanced S-Cone Syndrome. AB - The authors previously reported details on enhanced S-cone syndrome (ESCS) in a 23-year-old male patient with a homozygous NR2E3 mutation (p.Q350X) who developed large bilateral macular retinoschisis. Subsequent optical coherence tomography follow-up showed that although the large bilateral macular retinoschisis remained at the age of 28, there was dramatic improvement in the retinoschisis by the age 32, with bilateral resolution of the macular retinoschisis without any treatment by the age of 34. Although there is no established treatment for macular retinoschisis complicated by ESCS, this case demonstrated that intervention may not be required in some patients with ESCS. PMID- 26878456 TI - Traumatic Branch Retinal Vein Occlusion With Retinal Neovascularization Following Inadvertent Retrobulbar Needle Perforation. AB - Retrobulbar injection of anesthesia is one of the most common procedures performed for ophthalmic surgery. Complications are rare but can be potentially serious, including retrobulbar hemorrhage, brainstem anesthesia, and inadvertent globe perforation. This is the preliminary report describing branch retinal vein occlusion (BRVO) secondary to accidental retrobulbar needle laceration with subsequent preretinal neovascularization. PMID- 26878457 TI - 8 Questions with Dr. Puliafito. PMID- 26878458 TI - A search for blues brothers: X-ray crystallographic/spectroscopic characterization of the tetraarylbenzidine cation radical as a product of aging of solid magic blue. AB - Magic blue (MB+ SbCl6- salt), i.e. tris-4-bromophenylamminium cation radical, is a routinely employed one-electron oxidant that slowly decomposes in the solid state upon storage to form so called 'blues brothers', which often complicate the quantitative analyses of the oxidation processes. Herein, we disclose the identity of the main 'blues brother' as the cation radical and dication of tetrakis-(4-bromophenyl)benzidine (TAB) by a combined DFT and experimental approach, including isolation of TAB+ SbCl6- and its X-ray crystallography characterization. The formation of TAB in aged magic blue samples occurs by a Scholl-type coupling of a pair of MB followed by a loss of molecular bromine. The recognition of this fact led us to the rational design and synthesis of tris(2 bromo-4-tert-butylphenyl)amine, referred to as 'blues cousin' (BC: Eox1 = 0.78 V vs. Fc/Fc+, lambdamax(BC+) = 805 nm, epsilonmax = 9930 cm-1 M-1), whose oxidative dimerization is significantly hampered by positioning the sterically demanding tert-butyl groups at the para-positions of the aryl rings. A ready two-step synthesis of BC from triphenylamine and the high stability of its cation radical (BC+) promise that BC will serve as a ready replacement for MB and an oxidant of choice for mechanistic investigations of one-electron transfer processes in organic, inorganic, and organometallic transformations. PMID- 26878460 TI - Theoretical study of interactions of a Li(+)(CF3SO2)2N(-) ion pair with CR3(OCR2CR2)nOCR3 (R = H or F). AB - Interactions of a lithium bis(trifluoromethane sulfonyl)imide (Li(+)Tf2N(-)) ion pair with oligoethers are investigated via density functional theory (DFT). As a model for polymer electrolytes polyethyleneoxide (PEO) and perfluoropolyether (PFPE), CR3(OCR2CR2)n=1-5OCR3 (R = H or F) is considered. Topographical analysis of the molecular electrostatic potential (MESP) is performed to determine preferential binding sites of Li(+). Our study shows that the MESP value near the oxygen sites of the polymer backbone is more negative for PEO than for PFPE. This result indicates that substitution of hydrogen by fluorine in polyethers leads to reduction in Li(+)-polymer interactions, in concert with the experimental ionic conductivity results. S-O stretching vibrations of Tf2N(-) are calculated for the lithium salt in the presence and absence of electrolytes. The blue and red shifts predicted for S-O stretching are further explained by natural bond orbital analysis and molecular electron density topography. The S-O stretching vibrations can be used as a useful tool to understand the ion pair interactions and thus ion transport phenomena in polymer electrolytes. PMID- 26878459 TI - Bridging a clinical gap in psychogenic nonepileptic seizures: Mental health provider preferences of biopsychosocial assessment approaches. AB - Management of psychogenic nonepileptic seizures (PNES) is complex, requiring multidisciplinary care. A standardized assessment and formulation approach to PNES is lacking, yet use of a comprehensive model may alleviate problems such as mental health aftercare noncompliance. Although a biopsychosocial (BPS) approach to PNES balancing predisposing, precipitating, and perpetuating (PPP) variables has been described and has been recently tested in pilot form, it is unclear how this assessment style is perceived among community mental health practitioners such as psychotherapists (including psychologists, counselors, and social workers). We predicted preference of a comprehensive "BPS/PPP" assessment style by those most involved in PNES care (i.e., community psychotherapists). One hundred and forty-three community-based social workers and counselors completed a survey featuring a fictional PNES case followed by assessment style options ("Multiaxial," "Narrative," and "BPS/PPP"). Respondents clearly preferred the robust BPS/PPP approach over less-comprehensive multiaxial and narrative assessments (p<0.0001). Reasons for choosing the BPS/PPP by respondents include ease of organization, clear therapeutic goals, and comprehensive nature. This assessment of acceptability of a BPS/PPP approach to PNES assessment among community mental health practitioners may provide a patient-centered mechanism to enhance referrals from the neurological to mental health setting. Implications and future directions are explored. PMID- 26878461 TI - Order/Disorder and in Situ Oxide Defect Control in the Bixbyite Phase YPrO3+delta (0 <= delta < 0.5). AB - The YPrO3+delta system is a nearly ideal model system for the investigation of oxide defect creation and annihilation in oxide ion conductor related phases with potential applications as solid state electrolytes in solid oxide fuel cells. The formation, structure, high temperature reactivity, and magnetic susceptibility of phase pure YPrO3+delta (0 <= delta <= 0.46) are reported. The topotactic reduction and oxidation of the YPrO3+delta system was investigated by powder X ray in situ diffraction experiments and revealed bixbyite structures (space group: Ia3) throughout the series. Combined neutron and X-ray data clearly show oxygen uptake and removal. The research provides a detailed picture of the Y(3+)/Pr(3+)/Pr(4+) sublattice evolution in response to the redox chemistry. Upon oxidation, cation site splitting is observed where the cation in the ((1)/4, (1)/4, (1)/4) position migrates along the body diagonal to the (x, x, x) position. Any oxygen in excess of YPrO3.0 is located in the additional 16c site without depopulating the original 48e site. The in situ X-ray diffraction data and thermal gravimetric analysis have revealed the reversible topotactic redox reactivity at low temperatures (below 425 degrees C) for all compositions from YPrO3 to YPrO3.46. Magnetic susceptibility studies were utilized in order to further confirm praseodymium oxidation states. The linear relation between the cubic unit cell parameter and oxygen content allows for the straightforward determination of oxygen stoichiometry from X-ray diffraction data. The different synthesis strategies reported here are rationalized with the structural details and the reactivity of YPrO3+delta phases and provide guidelines for the targeted synthesis of these functional materials. PMID- 26878463 TI - Quantification of effects of cancer on elastic properties of breast tissue by Atomic Force Microscopy. AB - Different behaviors of cells such as growth, differentiation and apoptosis widely differ in case of diseases. The mechanical properties of cells and tissues can be used as a clue for diagnosis of pathological conditions. Here, we implemented Atomic Force Microscopy to evaluate the extent of alteration in mechanical stiffness of tissue layers from patients affected by breast cancer and investigated how data can be categorized based on pathological observations. To avoid predefined categories, Fuzzy-logic algorithm as a novel method was used to divide and categorize the derived Young's modulus coefficients (E). Such algorithm divides data among groups in such way that data of each group are mostly similar while dissimilar with other groups. The algorithm was run for different number of categories. Results showed that three (followed by two with small difference) groups categorized data best. Three categories were defined as (E<3000Pa, 30007000Pa) among which data were allocated. The first cluster was assumed as the cellular region while the last cluster was referred to the fibrous parts of the tissue. The intermediate region was due to other non cellular parts. Results indicated 50% decline of average Young's modulus of cellular region of cancerous tissues compared to healthy tissues. The average Young's modulus of non-cellular area of normal tissues was slightly lower than that of cancerous tissues, although the difference was not statistically different. Through clustering, the measured Young's moduli of different locations of cancerous tissues, a quantified approach was developed to analyze changes in elastic modulus of a spectrum of components of breast tissue which can be applied in diagnostic mechanisms of cancer development, since in cancer progression the softening cell body facilitates the migration of cancerous cells through the original tumor and endothelial junctions. PMID- 26878464 TI - Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential. AB - Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 MUg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 MUg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential. PMID- 26878466 TI - A new look at left ventricular remodeling definition by cardiac imaging. PMID- 26878465 TI - Abnormal glycemic homeostasis at the onset of serious mental illnesses: A common pathway. AB - OBJECTIVE: Patients with serious mental illnesses exhibit a reduced lifespan compared with the general population, a finding that can not solely rely on high suicide risk, low access to medical care and unhealthy lifestyle. The main causes of death are medical related pathologies such as type 2 diabetes mellitus and cardiovascular disease; however pharmacological treatment might play a role. MATERIAL AND METHODS: We compared a two hour glucose load in naive patients at the onset of a serious mental illness (N=102) (84 patients with a first episode of schizophrenia and related disorders, 6 with a first episode of bipolar I disorder and 12 with a first episode of major depression disorder) with another psychiatric diagnose, adjustment disorder (N=17) and matched controls (N=98). RESULTS: Young patients with serious mental illness showed an increased two hour glucose load compared with adjustment disorder and the control group. Mean two hour glucose values [+/-standard deviation] were: for schizophrenia and related disorders 106.51mg/dL [+/-32.0], for bipolar disorder 118.33mg/dL [+/-34.3], for major depressive disorder 107.42mg/dL [+/-34.5], for adjustment disorder 79.06mg/dL[+/-24.4] and for the control group 82.11mg/dL [+/-23.3] (p<0.001). CONCLUSIONS: Our results reflect an abnormal metabolic pathway at the onset of the disease before any pharmacological treatment or other confounding factors might have taken place. Our results suggest a similar glycemic pathway in serious mental illnesses and the subsequent need of primary and secondary prevention strategies. PMID- 26878467 TI - Two-year follow-up after bioresorbable vascular scaffold implantation in STEMI patients - Results from PRAGUE-19 study. PMID- 26878468 TI - Wellenoid T-wave is an important indicator for severe coronary artery stenosis. PMID- 26878469 TI - Contained coronary rupture following bioresorbable scaffold implantation in a small vessel. PMID- 26878471 TI - Effect of cardiac resynchronization therapy on right ventricular function. PMID- 26878470 TI - Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study. AB - OBJECTIVES: To evaluate the impact of age- and gender-specific cut-offs for high sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI). METHODS: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14ng/L to previously proposed age- and gender dependent hs-cTnT 99th percentile cut-offs (28ng/L for >=65years, 9ng/L for female and 15.5ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS. RESULTS: For patients >=65years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n=557) and 54.7% to 40.9% in the ACS subcohort (n=225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n=477) and 62.6% to 71.7% (ACS subcohort, n=99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n=805) and 48.8% to 45.9% (ACS, n=281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p<0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs. CONCLUSIONS: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation. PMID- 26878472 TI - Cholecystokinin in plasma predicts cardiovascular mortality in elderly females. AB - BACKGROUND: Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. METHODS: Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n=470). Primary care patients were followed for 13years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point. RESULTS: In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p<0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p=0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p=0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p=0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk. CONCLUSIONS: CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment. PMID- 26878473 TI - Percutaneous closure of ventricular septal defect with membraneous pouch and changing the device due to severe aortic regurgitation. PMID- 26878474 TI - The more proximal implantation of percutaneous mitral annuloplasty device due to the circumflex artery compression may be less beneficial. PMID- 26878475 TI - Revascularization treatment for spontaneous coronary artery dissection: A reconsideration of drug-coated balloons and bioresorbable vascular scaffold. PMID- 26878476 TI - Prevalence and characterization of bystander coronary artery disease in Tako tsubo cardiomyopathy using a multi-imaging approach. PMID- 26878477 TI - The traditional Japanese medicine hangeshashinto alleviates oral ulcer-induced pain in a rat model. AB - OBJECTIVE: Recent studies have demonstrated that mouthwash made with the traditional Japanese medicine hangeshashinto exhibits anti-inflammatory action and alleviates oral mucositis scores, including pain complaints, in patients undergoing chemoradiotherapy. However, no study has demonstrated the mechanism underlying how hangeshashinto provides pain relief in oral ulcers. DESIGN: The analgesic effects on pain-related behaviors following the topical application of hangeshashinto were evaluated in an oral ulcer rat model treated with acetic acid using recently developed methods. Indomethacin, the representative anti inflammatory agent, was intraperitoneally administered. The tissue permeability of the oral mucosa was histologically evaluated after applying the fluorescent substance FluoroGold. RESULTS: The topical application of hangeshashinto in ulcerative oral mucosa suppressed mechanical pain hypersensitivity over 60 min, without any effects on healthy mucosa. The same drug application also inhibited oral ulcer-induced spontaneous pain. Indomethacin administration failed to block the mechanical pain hypersensitivity, though it did largely block spontaneous pain. Topical anesthesia with lidocaine showed hyposensitivity to mechanical stimulation in healthy mucosa. In the ulcer regions in which the oral epithelial barrier was destroyed, deep parenchyma was stained with FluoroGold, in contrast to healthy oral mucosa, in which staining was limiting to the superficial site. CONCLUSIONS: Hangeshashinto leads to long-lasting analgesic effects, specifically in the ulcer region by destroying the epithelial barrier. Hangeshashinto alleviates oral ulcer-induced pain in inflammation-dependent and/or independent manner. PMID- 26878478 TI - Progesterone exerts neuroprotective effects against Abeta-induced neuroinflammation by attenuating ER stress in astrocytes. AB - The deposition of amyloid-beta (Abeta) and neuroinflammation are critical pathological features of Alzheimer's disease (AD). Astrocytes are considered the principal immunoregulatory cells in the brain. Neurosteroid progesterone (PG) exerts neuromodulatory properties, particularly its potential therapeutic function in ameliorating AD. However, the role of PG and the neuroprotective mechanism involving in the regulation of neuroinflammation in astrocytes warrant further investigation. In this study, we found that Abeta significantly increased the processing of neuroinflammatory responses in astrocytes. The processing is induced by an increase activity of PERK/elF2alpha-dependent endoplasmic reticulum (ER) stress. Additionally, the inhibition of ER stress activation by Salubrinal significantly suppressed the Abeta-induced neuroinflammatory responses in astrocytes. While the treatment of astrocytes with Abeta caused an increase of neuroinflammatory responses, PG significantly inhibited Abeta-induced neuroinflammatory cytokine production by suppressing ER stress activation together with attenuating PERK/elF2alpha signalling. Taken together, these results indicate that PG exerts a neuroprotective effect against Abeta-induced neuroinflammatory responses, and significantly suppresses ER stress activation, which is an important mediator of the neurotoxic events occurring in Abeta induced neuroinflammatory responses in astrocytes. These neuroprotective mechanisms may facilitate the development of therapies to ameliorate AD. PMID- 26878479 TI - Correlating the chemical and spectroscopic characteristics of natural organic matter with the photodegradation of sulfamerazine. AB - The role of aquatic natural organic matter (NOM) in the removal of contaminants of emerging concern has been widely studied. Sulfamerazine (SMR), a sulfonamide antibiotic detected in aquatic environments, is implicated in environmental toxicity and may contribute to the resistance of bacteria to antibiotics. In aquatic systems sulfonamides may undergo direct photodegradation, and, indirect photodegradation through the generation of reactive species. Because some forms of NOM inhibit the photodegradation there is an increasing interest in correlating the spectroscopic parameters of NOM as potential indicators of its degradation in natural waters. Under the conditions used in this study, SMR hydrolysis was shown to be negligible; however, direct photolysis is a significant in most of the solutions studied. Photodegradation was investigated using standard solutions of NOM: Suwannee River natural organic matter (SRNOM), Suwannee River humic acid (SRHA), Suwannee River fulvic acid (SRFA), and Aldrich humic acid (AHA). The steady-state concentrations and formation rates of the reactive species and the SMR degradation rate constants (k1) were correlated with NOM spectroscopic parameters determined using UV-vis absorption, excitation emission matrix (EEM) fluorescence spectroscopy, and proton nuclear magnetic resonance ((1)H NMR). SMR degradation rate constants (k1) were correlated with steady-state concentrations of NOM triplet-excited state ([(3)NOM(*)]ss) and the corresponding formation rates ((3)NOM*) for SRNOM, SRHA, and AHA. The efficiency of SMR degradation was highest in AHA solution and was inhibited in solutions of SRFA. The steady-state concentrations of singlet oxygen ([(1)O2]ss) and the SMR degradation rate constants with singlet oxygen (k1O2) were linearly correlated with the total fluorescence and inversely correlated with the carbohydrate/protein content ((1)H NMR) for all forms of NOM. The total fluorescence and EEMs Peak A were confirmed as indicators of (1)O2 formation. Specific ultraviolet absorbance at 254 nm (SUVA254) and aromaticity showed potential correlations with the steady-state concentrations of hydroxyl radical ([HO]ss) and the corresponding formation rates (HO). PMID- 26878480 TI - Surface-treated carbon electrodes with modified potential of zero charge for capacitive deionization. AB - The potential of zero charge (Epzc) of electrodes can greatly influence the salt removal capacity, charge efficiency and cyclic stability of capacitive deionization (CDI). Thus optimizing the Epzc of CDI electrodes is of great importance. A simple strategy to negatively shift the Epzc of CDI electrodes by modifying commercial activated carbon with quaternized poly (4-vinylpyridine) (AC QPVP) is reported in this work. The Epzc of the prepared AC-QPVP composite electrode is as negative as -0.745 V vs. Ag/AgCl. Benefiting from the optimized Epzc of electrodes, the asymmetric CDI cell which consists of the AC-QPVP electrode and a nitric acid treated activated carbon (AC-HNO3) electrode exhibits excellent CDI performance. For inverted CDI, the working potential window of the asymmetric CDI cell can reach 1.4 V, and its salt removal capacity can be as high as 9.6 mg/g. For extended voltage CDI, the salt removal capacity of the asymmetric CDI cell at 1.2/-1.2 V is 20.6 mg/g, which is comparable to that of membrane CDI using pristine activated carbon as the electrodes (19.5 mg/g). The present work provides a simple method to prepare highly positively charged CDI electrodes and may pave the way for the development of high-performance CDI cells. PMID- 26878481 TI - Limited accumulation of copper in heavy metal adapted mosses. AB - Copper is an essential micronutrient but has toxic effects at high concentrations. Bryophytes are remarkably tolerant to elevated levels of copper but we wondered if this tolerance might be species dependent. Therefore, in three moss species, Physcomitrella patens, Mielichhoferia elongata and Pohlia drummondii, the accumulation of copper was compared with semiquantitative SEM-EDX analyses after six weeks of cultivation on copper containing media. We investigated the role of the copper-linked anion and applied copper as CuCl2, CuSO4 and CuEDTA, respectively. Line scans along the growth axis of moss gametophores allowed for a detailed analysis of copper detection from the base towards the tip. Mosses originating from metal-containing habitats (i.e. M. elongata and P. drummondii) revealed a lower accumulation of copper when compared to the non-adapted P. patens. CuEDTA had a shielding effect in all three species and copper levels differed greatly from CuCl2 or CuSO4. The detection of reactive oxygen species (ROS), H2O2 and O2(-), was further used to indicate stress levels in the gametophore stems. ROS staining was increased along the whole stem and the tip in the non-adapted species P. patens whereas the tolerant species M. elongata and P. drummondii generally showed less staining located mainly at the base of the stem. We discuss the relation between metal accumulation and ROS production using indicator dyes in the three moss species. As moss gametophores are very delicate structures, ROS staining provide an excellent alternative to spectrophotometric analyses to estimate stress levels. PMID- 26878482 TI - Surface-patterned SU-8 cantilever arrays for preliminary screening of cardiac toxicity. AB - Arrays of a MUgrooved SU-8 cantilever were utilized to analyze changes in the contraction force and beating frequency of cardiomyocytes in vitro. The longitudinally patterned MUgrooves facilitates alignment of cardiomyocytes on top of the SU-8 cantilever, which increases the contraction force of cardiomyocytes by a factor of about 2.5. The bending displacement of the SU-8 cantilever was precisely measured in nanoscale using a laser-based measurement system combined with a motorized xyz stage. The cantilever displacement due to contraction of the cardiomyocytes showed the maximum on day 8 after their cultivation. Following preliminary experiments, Isoproterenol, Verapamil, and Astemizole were used to investigate the effect of drug toxicity on the physiology of cardiomyocytes. The experimental results indicated that 1 uM of Isoproterenol treatment increased contraction force and beating frequencies of cardiomyocytes by 30% and 200%, respectively, whereas 500 nM of Verapamil treatment decreased contraction force and beating frequencies of cardiomyocytes by 56% and 42%, respectively. A concentration of less than 5 nM of the hERG channel suppression drug Astemizole did not change the contraction forces in the displacement but slightly decreased the beating frequencies. However, irregular or abnormal heartbeats were observed at Astemizole concentrations of 5 nM and higher. We experimentally conformed that the proposed SU-8 cantilever arrays combined with the laser-based measurement systems has the great potential for a high-throughput drug toxicity screening system in future. PMID- 26878483 TI - Label-free cascade amplification strategy for sensitive visual detection of thrombin based on target-triggered hybridization chain reaction-mediated in situ generation of DNAzymes and Pt nanochains. AB - A new magnetic bead-based cascade amplification strategy for highly sensitive visual detection of proteins (thrombin as a model analyte) was developed by coupling target-triggered hybridization chain reaction (HCR) with the synergistic catalysis of DNA concatemer-mediated hemin/G-quadruplex DNAzymes and Pt nanozymes. Initially, the biotinylated primer DNA (P-DNA) was complementary with aptamer to form dsDNA which was further linked to streptavidin-coated magnetic bead (MB), thereby fabricating the expected MB-based aptasensor. In the presence of target TB, the aptamer was taken away from the aptasensor, and the free P-DNA immediately triggered HCR to spontaneously form DNA concatemer-directed nanochains with numerous DNAzymes and Pt nanoclusters (PtNCs) to achieve cascades signal amplification. The dual peroxidase mimetics catalyzed the H2O2-mediated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) into the colored TMB oxides (oxTMB), causing intensified color change of the chromogenic solution for the highly sensitive naked-eye detection of as low as 100.0 pM TB. In this strategy, the employment of magnetic separation and exonuclease III (Exo III) assisted digestion of residual dsDNA minimized the background noise and avoided the false positive results, greatly improving the detection accuracy and sensitivity with a low limit of detection (LOD=15.0 pM). The proposed visual platform has promise for detecting various types of proteins with careful DNA sequence designs. PMID- 26878484 TI - Signal-on electrochemical detection of antibiotics at zeptomole level based on target-aptamer binding triggered multiple recycling amplification. AB - In the work, a signal-on electrochemical DNA sensor based on multiple amplification for ultrasensitive detection of antibiotics has been reported. In the presence of target, the ingeniously designed hairpin probe (HP1) is opened and the polymerase-assisted target recycling amplification is triggered, resulting in autonomous generation of secondary target. It is worth noting that the produced secondary target could not only hybridize with other HP1, but also displace the Helper from the electrode. Consequently, methylene blue labeled HP2 forms a "close" probe structure, and the increase of signal is monitored. The increasing current provides an ultrasensitive electrochemical detection for antibiotics down to 1.3 fM. To our best knowledge, such work is the first report about multiple recycling amplification combing with signal-on sensing strategy, which has been utilized for quantitative determination of antibiotics. It would be further used as a general strategy associated with more analytical techniques toward the detection of a wide spectrum of analytes. Thus, it holds great potential for the development of ultrasensitive biosensing platform for the applications in bioanalysis, disease diagnostics, and clinical biomedicine. PMID- 26878485 TI - Quantum dot monolayer for surface plasmon resonance signal enhancement and DNA hybridization detection. AB - We report results of studies relating to the fabrication of a surface plasmon resonance (SPR)-based nucleic acid sensor for quantification of DNA sequence specific to chronic myelogeneous leukemia (CML). The SPR disk surface has been modified with octadecanethiol self-assembled monolayer followed by deposition of the tri-n-octylphosphine oxide capped cadmium selenide quantum dots (QD) Langmuir monolayer. The deposition is performed via Langmuir-Blodgett (LB) technique. For the sensor chip preparation, covalent immobilization of the thiol-terminated DNA probe sequence (pDNA) using displacement reaction is accomplished. This integrated SPR chip has been used to detect target complementary DNA concentration by monitoring the change in coupling angle via hybridization. It is revealed that this biosensor exhibits high sensitivity (0.7859 m(0)pM(-1)) towards complementary DNA and can be used to detect it in the concentration range, 180 pM to 5 pM with detection limit as 4.21 pM. The results of kinetic studies yield the values of hybridization and dissociation rate constants as 9.6 * 10(4) M(-1) s(-1) and 2.3 * 10(-2) s(-1), respectively, with the equilibrium constant for hybridization as 4.2 * 10(6) M(-1). PMID- 26878487 TI - Ring inversion properties of 1->2, 1->3 and 1->6-linked hexopyranoses and their correlation with the conformation of glycosidic linkages. AB - Enhanced-sampling molecular dynamics simulations performed within the GROMOS 56a6CARBO_R force field were applied in order to elucidate ring-inversion properties of hexopyranose residues in a chain for the case of alpha(1->n) and beta(1->n) glycosidic linkages (n = 2, 3 or 6). The results indicate that ring inversion free energies calculated for residues in a chain are weakly correlated with those of corresponding monomers, except of the case of 1->6 linkages. This, in combination with the results for O1-methyl-hexopyranosides (Plazinski et al, 2016), suggests that both the type of functionalization (glycolysation vs. methylation) and the topology of glycosidic linkage play an important role in possible alterations of the hexopyranose ring flexibility. Additionally, the correlation of the ring shape with the preferred geometry of glycosidic linkages was investigated. The linkages of the 1->2, 1->3 and 1->6 types do not follow the trend found in the case of the 1->4 linkages, i.e. there is no correlation between the range of changes in the glycosidic linkage conformation and the topological orientation of the glycosidic oxygen atoms. Overall, the ring shape affects the glycosidic linkages of the 1->6 type to the least extent in comparison to the remaining ones. PMID- 26878486 TI - Marine cytotoxic jaspine B and its stereoisomers: biological activity and syntheses. AB - Conformationally constrained sphingolipids such as anhydrophytosphingosines represented by jaspine B (also known as pachastrissamine) and its stereoisomers have become an attractive and timely target for total synthesis due to their significant biological activity as well as the unique structures. This review article describes the biological activity and chemistry of the natural jaspine B and its seven stereoisomers. PMID- 26878488 TI - Influence of intramolecular hydrogen bonds on regioselectivity of glycosylation. Synthesis of lupane-type saponins bearing the OSW-1 saponin disaccharide unit and its isomers. AB - A series of lupane-type saponins bearing OSW-1 disaccharide unit as well as its regio- and stereoisomers were prepared and used for the structure-activity relationships (SAR) study. Unexpected preference for 1->4-linked regioisomers and an unusual inversion of the conformation of the sugar rings were noted. Cytotoxic activity of new lupane compounds was evaluated in vitro and revealed that some saponins exhibited an interesting bioactivity profile against human cancer cell lines. Influence of the protecting groups on the cytotoxicity was investigated. These results open the way to the synthesis of various lupane-type triterpene and saponin derivatives as potential anticancer compounds. PMID- 26878489 TI - Layered Perovskite Oxychloride Bi4NbO8Cl: A Stable Visible Light Responsive Photocatalyst for Water Splitting. AB - Mixed anion compounds are expected to be a photocatalyst for visible light induced water splitting, but the available materials have been almost limited to oxynitrides. Here, we show that an oxychrolide Bi4NbO8Cl, a single layer Sillen Aurivillius perovskite, is a stable and efficient O2-evolving photocatalyst under visible light, enabling a Z-scheme overall water splitting by coupling with a H2 evolving photocatalyst (Rh-doped SrTiO3). It is found that the valence band maximum of Bi4NbO8Cl is unusually high owing to highly dispersive O-2p orbitals (not Cl-3p orbitals), affording the narrow band gap and possibly the stability against water oxidation. This study suggests that a family of Sillen-Aurivillius perovskite oxyhalides is a promising system to allow a versatile band level tuning for establishing efficient and stable water-splitting under visible light. PMID- 26878490 TI - Advancing health equity to improve health: the time is now. AB - Health inequities, or avoidable inequalities in health between groups of people, are increasingly recognized and tackled to improve public health. Canada's interest in health inequities goes back over 40 years, with the landmark 1974 Lalonde report, and continues with the 2011 Rio Political Declaration on Social Determinants of Health, which affirmed a global political commitment to implementing a social determinants of health approach to reducing health inequities. Research in this area includes documenting and tracking health inequalities, exploring their multidimensional causes, and developing and evaluating ways to address them. Inequalities can be observed in who is vulnerable to infectious and chronic diseases, the impact of health promotion and disease prevention efforts, how disease progresses, and the outcomes of treatment. Many programs, policies and projects with potential impacts on health equity and determinants of health have been implemented across Canada. Recent theoretical and methodological advances in the areas of implementation science and population health intervention research have strengthened our capacity to develop effective interventions. With the launch of a new health equity series this month, the journals Canada Communicable Disease Report and Health Promotion and Chronic Disease Prevention in Canada will continue to reflect and foster analysis of social determinants of health and focus on intervention studies that advance health equity. PMID- 26878491 TI - Socioeconomic gradients in cardiovascular risk in Canadian children and adolescents. AB - INTRODUCTION: Cardiovascular disease (CVD) and its risk factors show clear socioeconomic gradients in Canadian adults. Whether socioeconomic gradients in cardiovascular risk emerge in childhood remains unclear. The objective of this study was to determine whether there are socioeconomic gradients in physiological markers of CVD risk in Canadian children and adolescents. METHODS: Using combined cross-sectional data from the Canadian Health Measures Survey 2007-2011, we examined the following cardiovascular risk markers: overweight (including obesity), aerobic fitness score (AFS), blood pressure (BP), blood lipids (total as well as HDL and LDL cholesterol and triglycerides), glucose metabolism and C reactive protein (CRP) by sex in 2149 children (ages 6-11 years) and 2073 adolescents (ages 12-17 years). Multivariate linear and logistic regression analyses were used to identify patterns in cardiovascular risk across strata of household income adequacy and parental educational attainment, adjusting for age and ethnicity, and stratified by age group and sex. RESULTS: Young boys showed markedly higher prevalence of obesity than young girls (prevalence of 18.5%, 95% confidence interval [CI]: 15.6-21.5 vs. 7.7%, 95% CI: 5.2-10.3). However, negative SES gradients in adiposity risk were seen in young and adolescent girls rather than boys. Young and adolescent boys were more physically fit than girls (mean AFS of 541, 95% CI: 534-546 vs. 501, 95% CI: 498-505 in children; 522, 95% CI: 514-529 vs. 460, 95% CI: 454-466 in adolescents; p < 001). Although a positive income gradient in AFS was observed in both boys and girls, statistical significance was reached only in girls (p =.006). A negative gradient of parental education in BP was observed in young children. While we observed substantial sex differences in systolic BP, total and HDL cholesterol, fasting glucose and CRP in adolescents, sex-specific socioeconomic gradients were only observed for systolic BP, HDL and LDL cholesterol. Further studies with large samples are needed to confirm these findings. CONCLUSION: This study identified important sex difference and socioeconomic gradients in adiposity, aerobic fitness and physiological markers of CVD risk in Canadian school-aged children. Population health interventions to reduce socioeconomic gradients in CVD risk should start in childhood, with a particular focus on preventing obesity in young boys of all SES and girls of low SES, promoting physical fitness especially in girls and in all ages of youth in low-SES groups, and increasing parental awareness, especially those with low educational attainment, of early CVD risks in their children. PMID- 26878493 TI - Strengthening the evidence base on social determinants of health: measuring everyday discrimination through a CCHS rapid response module. PMID- 26878492 TI - Prevalence of metabolic syndrome and its risk factors in Canadian children and adolescents: Canadian Health Measures Survey Cycle 1 (2007-2009) and Cycle 2 (2009-2011). AB - INTRODUCTION: We investigated the prevalence of metabolic syndrome (MetS) and its risk factors, and the influence of socioeconomic status, in Canadian children and adolescents. METHODS: Canadian Health Measures Survey cycle 1 (2007-2009) and cycle 2 (2009-2011) respondents aged 10 to 18 years who provided fasting blood samples were included (n = 1228). The International Diabetes Federation (IDF) consensus definition for children and adolescents (10-15 years) and worldwide adult definition (>= 16 years) were used to diagnose MetS. Prevalence of MetS and its risk factors were calculated and differences by socioeconomic status were examined using chi2 tests. RESULTS: The prevalence of MetS was 2.1%. One-third (37.7%) of participants had at least one risk factor, with the most prevalent being abdominal obesity (21.6%), low HDL-C (19.1%) and elevated triglyceride levels (7.9%). This combination of abdominal obesity, low HDL-C and elevated triglyceride levels accounted for 61.5% of MetS cases. Participants from households with the highest income adequacy and educational attainment levels had the lowest prevalence of one or more MetS risk factors, abdominal obesity and low HDL-C. CONCLUSION: The prevalence of MetS (2.1%) was lower than previously reported in Canada (3.5%) and the USA (4.2%!-9.2%), potentially due to the strict application of the IDF criteria for studying MetS. One-third of Canadian children and adolescents have at least one risk factor for MetS. Given that the risk for MetS increases with age, these prevalence estimates, coupled with a national obesity prevalence of almost 10% among youth, point to a growing risk of MetS and other chronic diseases for Canadian youth. PMID- 26878495 TI - Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics. AB - INTRODUCTION: Second-generation antipsychotics (SGAs) are frequently co prescribed with drug metabolic inducers and inhibitors. SGA pharmacokinetic drug drug interactions (DDIs) with inducers and inhibitors have not received enough attention in the literature but can be studied in by using therapeutic drug monitoring (TDM). AREAS COVERED: The limited information available on oral SGA pharmacokinetic DDIs is reviewed. A systematic literature search on the available oral SGA TDM studies is completed. By integrating TDM studies with the information on in vitro metabolism studies, case report/series and prospective studies, a table is provided to manage average SGA patients taking inducers or inhibitors by using TDM and/or dose SGA changes. Adding an inhibitor or discontinuing an inducer may increase plasma concentrations and cause adverse drug reactions (ADRs) on clozapine or risperidone. Quetiapine and lurasidone, which are very sensitive to decreases of plasma concentrations by induction, should not be administered with potent inducers. Prescribing sertindole with TDM may make its use safer. EXPERT OPINION: Reading our article may encourage: 1) clinicians using these combinations to publish TDM case reports/series to demonstrate whether our dose indications are correct or not, in their patients with DDIs; and 2) pharmacokinetic researchers to study these DDIs in prospective and retrospective ways using large TDM databases. PMID- 26878494 TI - Risk behaviours for HIV infection among travelling Mexican migrants: The Mexico US border as a contextual risk factor. AB - The Mexico-US border region is a transit point in the trajectory of Mexican migrants travelling to and from the USA and a final destination for domestic migrants from other regions in Mexico. This region also represents a high-risk environment that may increase risk for HIV among migrants and the communities they connect. We conducted a cross-sectional, population-based survey, in Tijuana, Mexico, and compared Mexican migrants with a recent stay on the Mexico US border region (Border, n = 553) with migrants arriving at the border from Mexican sending communities (Northbound, n = 1077). After controlling for demographics and migration history, border migrants were more likely to perceive their risk for HIV infection as high in this region and regard this area as a liberal place for sexual behaviours compared to Northbound migrants reporting on their perceptions of the sending communities (p < .05). Male border migrants were more likely to engage in sex, and have unprotected sex, with female sex workers during their recent stay on the border compared to other contexts (rate ratio = 3.0 and 6.6, respectively, p < .05). Binational and intensified interventions targeting Mexican migrants should be deployed in the Mexican border region to address migration related HIV transmission in Mexico and the USA. PMID- 26878496 TI - Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar. AB - Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 +/- 5.38 versus 24.77 +/- 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 +/- 3.39 versus 3.01 +/- 2.6; P = 0.006) and QUICKI (0.140 +/- 0.013 versus 0.147 +/- 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 +/- 3.91 versus 10.32 +/- 2.22; P = 0.01) and serum total testosterone levels (0.65 +/- 0.69 versus 0.86 +/- 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region. PMID- 26878497 TI - Effectiveness of platelets rich plasma versus corticosteroids in lateral epicondylitis. AB - OBJECTIVE: To compare the treatment modalities of lateral epicondylitis in terms of pain relief. METHODS: The randomised controlled study was conducted at Hayatabad Medical Complex, Peshawar, Pakistan, from April 2013 to March 2014, and comprised cases of lateral epicondylitis. The patients were selected through consecutive sampling from the outpatient department and were randomly allocated to two equal groups; group A receiving corticosteroid injections, and group B receiving injection of platelet-rich plasma. The patients were followed up for three weeks to determine the effectiveness of intervention. RESULTS: The 102 patients in the study were divided into two groups of 51(50%) each. The over mean age was 33.9+/-10.3 years. Mean age of patients in the corticosteroid group was 34.2+/-10.2 years and in the other group it was 33.6+/-10.5 years. Mean baseline visual analogue score in group A were 6.5+/-1.2 and in group B it was 6.7+/-1.4. In group A, 74.5% of patients presented in moderate pain category and 25.5% presented in severe pain category. In group B, 70.6% presented in moderate with 29.4% presented in severe pain category. On follow-up, the mean pain score in group A was 4.0+/-2.6 and in group B it was 3.5+/-2.61. Group A showed effectiveness in 52.9% patients and group B showed effectiveness in 82.3% (p=0.001). CONCLUSIONS: PRP is an effective alternate to corticosteroid in the treatment of lateral epicondylitis (tennis elbow). PMID- 26878498 TI - Local recurrence of giant cell tumour of bone after intralesional treatment with and without adjuvant therapy, a single institution case series. AB - BACKGROUND: Giant cell tumour (GCT) of bone is generally a benign tumour composed of mononuclear stromal cells and characteristic multinucleated giant cells that exhibit osteoclastic activity. It usually develops in long bones but can occur in unusual locations. The typical appearance is a lytic lesion with a well-defined but non-sclerotic margin that is eccentric in location, extends near the articular surface, and occurs in patients with closed physes. OBJECTIVE: The current study was planned to summarise our experiences with GCTB, and to evaluate individual effect of bone cement, high-speed burring and hydrogen per oxide (H2O2) on local recurrence. GCT can mimic or be mimicked by other benign or malignant lesions at both radiological evaluation and histological analysis. In the past, the mainstay of treatment was surgical, primarily consisting of curettage with cement placement, with recurrence rates of 15%-25%. Recurrence is suggested by development of progressive lucency at the cement-bone interface. RESULTS: Of the 21 patients who started the study, 4(19%) were lost to follow-up, and 17(81%) represented the final study sample. Of them, 16(94.11%) patients underwent the curettage procedure with adjuvant therapy and reconstruction with bone grafts taken from iliac crest. In 3(26.3%) patients, no adjuvant was used. Total of 6 (42.1%) patients had local recurrence and 3(50%) of them were those who were treated without any adjuvant; 2(33.3%) with phenol and 1(16.6%) with PMMA. CONCLUSIONS: The results of the present study suggest that an "aggressive curettage" with the use of adjuvant reduces the recurrence rate in a disease whose aggressiveness is not easy to predict. PMID- 26878499 TI - Focal dome osteotomy for correction of varus deformity at elbow in children. AB - BACKGROUND: Cubitus varus is the most common complication of un-treated or mal treated supracondylar fracture of humerus at elbow. Various osteotomies have been described to correct this deformity but each is associated with its own complications. In this study, focal dome osteotomy for correction of cubitus varus was performed to determine its functional and radiological outcome. MATERIALS AND METHOD: In this study, 35 children with cubitus varus deformity were admitted from Jan 2009- Jan 2013. Clinical assessment was done before the procedure by measuring the carrying angle at elbow joint. Radiographic assessment of deformity was done by anteroposterior (AP) radiographs of the elbow by measuring the humeral-ulnar angle (HUA) and metaphyseal-diaphyseal angle (MDA). Through anterolateral approach, supracondylar region of humerus was exposed and focal dome osteotomy was done at the center of rotation of angulation (CORA). Final assessment was done clinically for carrying angle and radiologically for HUA and MDA at 8 weeks to evaluate the functional and radiological outcome as good or poor. RESULTS: The mean age of 35 children at the time of surgery was (mean +/- SD 8.03 +/- 2.35) with range from 5 - 12 years, Male to female ratio was 1.50:1. The mean duration of injury was (170.26 +/- 41.78) days. The functional outcome for carrying angle improved from 1.49 +/- 5.95 to 14.46 +/ 1.44 with p value <0.05. Radiological outcome for humeral-ulnar and metaphyseal diaphyseal angle improved from 27.71 +/- 4.31 to 17.77 +/- 1.23 and 103.66 +/- 4.76 to 90.49 +/- 1.96 with p value <0.05 respectively. The final Functional and Radiological outcome was good in 32 patients (91%) and poor in 3 patients (9%). CONCLUSIONS: Focal dome osteotomy is safe and stable method of correction of cubitus varus which avoids prominence of lateral condyle and is cosmetically acceptable. PMID- 26878500 TI - A comparison of functional outcome of intercondylar fracture of distal humerus managed by olecranon osteotomy approach versus triceps sparing approach in adults. AB - OBJECTIVE: To compare the frequency of satisfactory functional outcome of intercondylar fractures of distal humerus managed by the triceps-sparing approach and olecranon osteotomy approach. METHODS: The randomised controlled study was conducted at Mayo Hospital, Lahore, from September 1, 2012 to August31 2014,and comprised patients> 14 years of age who were admitted through the Accident and Emergency Department and were prepared for surgery to repair intercondylar fractures of distal humerus. The patients were randomly divided into two equal groups. Implants were arranged preoperatively. Patients in group A were managed by open reduction internal fixationvia olecranon osteotomy approach, and those in group B were managed by open reduction internal fixationvia triceps-sparing approach by the same team of surgeons. Mayo Elbow Performance Score was used to assess the functional outcome. Demographic, preoperative and postoperative clinical information of all patients were entered into a predesigned proforma and variables were evaluated statistically. RESULTS: The 150 patients in the study were randomly divided into two groups of 75(50%) patients each. The overall mean age was 49.01+/-14.63 years. Mean age of group A patients was 53.84+/-11.86 years and that of group B was 44.19+/-15.59 years. In group A, there were 67(89.3%) patients who had satisfactory functional outcome and 8(10.7%) had unsatisfactory outcome. In groupB,53(70.7%) patients had satisfactory and 22(29.3%) patients had unsatisfactory functional outcome. CONCLUSIONS: Olecranonosteotomy approach was found to be more effective and preferable compared to the triceps-sparing approach. PMID- 26878501 TI - Awareness of osteoporosis in men. AB - OBJECTIVE: To assess the awareness in office workers about osteoporosis in men. METHODS: The cross-sectional study was conducted in different offices in the 5 districts of Karachi from June to December 2014, and comprised office workers not related to the medical profession and belonging to middle and upper socioeconomic groups with education level of Masters and above. A questionnaire was used as the data collection tool and the collected data was analysed using SPSS 16. RESULTS: A total of 420 questionnaires were distributed of which 360(86%) were analysed. The mean age of the respondents was 44+/-9.11 years; mean height was 5.6+/-0.26 feet; mean weight was 70.8+/-1.20 kg; and 55% (198) participants were smokers. Only 14.7%(53) had heard of osteoporosis,13.3%(48) had heard of osteoporotic fracture, 17.5%(63) knew that osteoporosis can occur in males also,14.2%(51) knew that osteoporosis occurs secondary to smoking and alcohol consumption, 15%(54) knew worldwide 1 in every 8 males after 60 years suffers from osteoporosis, 22.5%(81) knew that it can be prevented with adequate calcium and vitamin D, and 30%(108) used internet to seek information regarding medical issues. In total, 54.4%(196) reported regular milk intake, 22.5%(81) took calcium supplements,23.6%(85) took vitamin D, 33.1%(85)performed regular exercise, 18.1%(65) had got their serum calcium and vitamin D levels checked. There was no association between smoking and the level of awareness (p=0.219). There was significant association between those who took calcium and the level of awareness (p=0.00), and between those who performed regular physical exercise and their level of awareness (P=0.001). CONCLUSIONS: There is a need to educate people as well as healthcare providers about the need to keep an eye on male osteoporosis. National awareness strategies should be implemented to cope with the issue. PMID- 26878502 TI - Effect of the silicone heel pad on plantar fasciitis. AB - OBJECTIVE: To evaluate the effect of silicone heel pad in the management of pain in plantar fasciitis patients. METHODS: The descriptive case series study was conducted at Hope Rehabilitation Centre, Lahore, from March 1 to September 30, 2013, and comprised patients aged > 18 years with symptomatic plantar fasciitis who were treated with silicone heel pad. All patients were assessed at one month and six months for pain relief measured on % Maximum Total Pain Relief and Pain Intensity Difference percentage scales. Data was analysed using SPSS 20. RESULTS: Out of 100 patients, 37(37%) were male and 63(63%) were female. The mean age of the patients was 44.25+/-12.75 years. Five (5%) patients were lost to follow-up during the study, while 7(7%) patients changed their initial treatment because they did not experience relief. Silicone heel pad reported a better outcome measure associated with the patient?'s heel pain as 74(84.09%) patients resolved their condition or reached a tolerance level and showed preferable reduction in heel pain .There were statistically significant difference between pain relieved and treatment duration (p=0.039). CONCLUSIONS: Conservative intervention with silicone heel pad showed relief from heel pain and it allowed the patient to manage the condition more effectively with no complications but for shortterm. It was less effective in the long term. PMID- 26878503 TI - Role of addition of Dexamethasone and Ketorolac to lignocaine intravenous regional anesthesia (Bier's Block) to improve tourniquet tolerance and post operative analgesia in hand and forearm surgery. AB - OBJECTIVE: To compare tourniquet tolerance and postoperative analgesia using lignocaine intravenous regional analgesia alone or with addition of dexamethasone and ketorolac. METHODS: The randomised, prospective study was conducted at Mayo Hospital, Lahore, from June 2013 to June 2014. Patients were divided into three groups: group I received lignocaine; group II received lignocaine and 30mg ketorolac; and group III received lignocaine, 30mg ketorolac and 08mg dexamethasone for intravenous regional anaesthesia. A total of 40ml solution was made by diluting it with normal saline. Motor and sensory block and recovery times were noted. Visual analogue scale was used to assess the severity of surgical and tourniquet pain, and total number of analgesic tablets taken in the first 24 hours after surgery were also recorded. RESULTS: The 180 patients in the study were divided into three equal groups of 60(33.3%) each, with each group having 30(50%) male and 30(50%) female subjects. In all the three groups, the sensory and motor onset and recovery time was the same (P> 0.05). Lower pain scores were reported in groups II and III compared to group I (p<0.001). Patients of group II and III also required fewer analgesic tablets postoperatively and had longer postop time during which no analgesia was given compared to group I (p<0.05). CONCLUSIONS: Bier block using lignocaine, dexamethasone and ketorolac provides better tourniquet tolerance in patients undergoing hand and forearm surgeries when compared to use of lignocaine alone and lignocaine and ketorolac. PMID- 26878504 TI - Bomb blast injuries: Tertiary care hospital in-patient experience over the last 20 years. AB - OBJECTIVE: To examine the distribution and nature of limb injuries in young bomb blast victimsand their management in a tertiary healthcare setting. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi and data was searched using the University Medical Record Database with International Classification of Diseases-Ninth Revision-Clinical Modification codes for injuries and terrorism between 1990 and 2012. Data regarding injuries, including admission time, hospital stay duration, interventions and mortality, was collected and classified as per the New Injury Severity Score. RESULTS: There were 22 patients in the study; 19(86.3%) males and 3(13.7%) females. The mean age of the sample was 13.1+/-4.1 years. Median length of hospital stay was 9 days (range: 2-42 days). Sixteen (72.7%) patients required operative intervention. Patients rarely had accompanying injuries with limb injuries. Four (18%) patients needed open reduction and internal fixation. Two (9%) patients needed open reduction and external fixation. One (4.5%) patient required a limb amputation. One (4.5%) patient required ileal resection with ileoileal anastomosis due to shrapnel perforations. There was no mortality. CONCLUSIONS: The young age group was not severely affected by limb trauma. Injuries sustained were infrequently accompanied by severe/critical injury severity scores. PMID- 26878505 TI - Antibiotic prophylaxis in hip surgery: A comparision of two vs. three doses of cefuroxime. AB - OBJECTIVE: To compare the efficacy of two-dose regime with a three-dose regime of cefuroxime in the prevention of post-operative wound infection in hip surgery patients and to determine the most effective regime of antibiotic prophylaxis for such patients. METHODS: The prospective, comparative, multi-centre cohort study was conducted from January 1998 to June 1998 at Dundee Royal Infirmary and attached district hospitals (Stirling Royal Infirmary and Falkirk Royal Infirmary). It comprised patients who had hip surgery i.e. fracture fixation, hemiarthroplasty or total hip replacement. Patients were assigned to two groups. Group A patients received cefuroxime 750mg at induction of anaesthesia and 750mg at the end of the procedure, while Group B patients received 1.5gm of cefuroxime at the induction of anaesthesia, followed by 750mg 8 and 16 hours after the operation. Patients were assessed post-operatively daily according to the ASEPSIS wound scoring system during the hospital stay. RESULTS: There were 280 patients in the study, with 140(50%) in each of the two groups. In Group A 60(43%) patients required fracture fixation, the rate of wound infection was 2(3.3%), 40(28.5%) required hemiarthroplasty and the rate of wound infection was 1(2.5%) and 40(28.5%) required total hip replacement and the rate of wound infection was zero. In Group B, the corresponding numbers were 1/60 (1.6%), 1/40 (2.5%) and zero. No evidence of minor, moderate or severe wound infection was observed in 272(97%) patients regardless of the group. The most frequent pathogens were Staphylococcus aureus in 3(1%) patients and Staphylococcus epidermidis in 2(0.7%). CONCLUSIONS: There was no significant difference in the prevalence of wound infection between the patients who had received two or three doses of cefuroxime. PMID- 26878506 TI - Outcome of hemivertebra resection in congenital thoracolumbar kyphosis and scoliosis by posterior approach. AB - OBJECTIVE: To find out the long term outcome of deformity correction by hemivertebra resection in congenital thoracolumbar spinal deformities by a single posterior approach. METHODS: This is a retrospective study carried out at the Department of Spine Surgery, Combined Military Hospital, Rawalpindi, Pakistan from April 2006 to April 2013. All operated patients having single level hemivertebrae of thoracolumbar spine with at least two years follow up were included. Data was analyzed using SPSS ver. 17. RESULTS: There were 24 patients with mean age of 17 years (SD=8.41). Male to female ratio was 9(37.5%): 15(62.5%). Mean operation time was 4.23 hours (SD=1.2). Mean blood loss was 787 ml (SD=479). Mean follow up was for 5 years and 7 months (SD=30 months). Mean pre op scoliosis was 51 degrees (SD=22), which improved to 20 degrees (SD=15) on last follow up (61% improvement). Mean pre-op kyphosis was 42 degrees (SD=35), which improved to 13 degrees (SD=15) on last follow up (69% improvement). Mean pre-op sagittal shift was 22mm (SD=24.9), which improved to 6mm (SD=9.37) on last follow up (73% improvement). Mean pre-op coronal shift was 34mm (SD=27.1), which improved to 8mm (SD=8.58) on last follow up (76% improvement). Five patients had complications. One proximal junctional kyphosis, one implant failure, one transient deficit and two wound infections. CONCLUSIONS: Posterior resection of hemivertebrae for congenital thoracolumbar deformities gives excellent correction of deformity in experienced hands and has acceptable complication rate. PMID- 26878507 TI - Outcome of ilizarov fixator in complex non-union of long bones. AB - OBJECTIVE: To evaluate the efficacy of Ilizarov fixator in the management of complex non-union of long bones. METHODS: The retrospective study was conducted at Ayub Teaching Hospital, Abbottabad, and Khyber Teaching Hospital, Peshawar, Pakistan, and comprised data of patients aged 14- 60 years of either gender with complex non-union of long bones between January 2006 and December 2013. Data, including age, gender, mechanism of injury, type of long bone involved, complications of surgery and final outcome, was documented on a pre-designed proforma. Outcome was graded using Association for the Study and Application of Methods of Ilizarov scoring system. SPSS 20 was used for analysis. RESULTS: There were 45 patients of whom 30(66.7%) were males and 15(33.4%) were females. The overall mean age was 32.20+/-12.48 years (range: 14-60 years).Of the 45 non unions, 39(86%) healed successfully, and the mean time to union was 30.69+/-8.6 weeks (range: 16-52weeks).In terms of outcome, 29(64.44%) patients had excellent bone results, 9(20%) had good results, 2(4.44%) had fair results and 5(11.1%) had poor bone results. There were 32(71.11%) patients with excellent functional result, 8(17.77%) good, 2(4.44%) fair and 3(6.66%) patients had poor results. CONCLUSIONS: Ilizarov fixator gave good and excellent results in complex non union of long bones by eradicating the infection, filling the defect with bone transport, and correcting the deformity and limb length discrepancy. PMID- 26878508 TI - Multi level lumbosacral spinal fusion including lumbo-Sacral (L5-S1) junction fixation in adult deformity surgery; is postero- lateral fusion at (L5-S1) alone adequate? AB - BACKGROUND/AIMS: To assess the revision rate at L5-S1 when only posterior fixation with pedicle screws is done with multi-level spinal fixation. PATIENTS AND METHODS: The Retrospective quasi experimental study was conducted at the Combined Military Hospital, Rawalpinidi and comprised data from 2009 to 2014 of patients in whom multi-level posterior decompression including lumbosacral junction (L5-S1) with laminectomy and posterior fixation with pedicle screws was done till L3 and higher. Those with known cause of implant failure like osteoporosis, osteomalacia and infection were excluded. Patients were followed up and need for revision at L5-S1 level was assessed. RESULTS: Of the 22 cases, 5(23%) were males and 17(77%) were females with an overall mean age of 64+/-10.38 years (range 48-84 years). Mean number of levels fixed was 5.22+/-1.15 the highest level of fixation being T11. Mean follow-up was 08+/-3.22 months and focused only at the failure of fixation at L5-S1. Two (9%) cases showed implant loosening and required revision at L5-S1 because of screw cut out. CONCLUSIONS: Properly placed pedicle screws were adequate with fusion for multilevel spinal fixations. PMID- 26878509 TI - A comparison of treating Unicameral bone cyst using steroids and percutaneous autologous bone marrow aspiration injection. AB - OBJECTIVE: To compare the results of percutaneous autologous bone aspiration injection and steroids injections in the treatment of unicameral bone cyst. METHODS: The prospective study was conducted at Mayo Hospital, Lahore, from January 2008 to March 2014, and comprised patients diagnosed radiologically as a case of unicameral bone cyst. The patients were divided into two groups, with group 1 being treated with bone marrow aspiration injection, while group 2 was given steroids injection. Aspiration of bone marrow was done from tibial tuberosity. RESULTS: The 30 patients in the study were divided into two groups of 15(50%) each. In group 1, 8(53.34%) patients and in group 2, 3 (20%) patients achieved healing after the first injection (p<0.05), while overall success rates were 13(86.67%) in group 1, and 11(73.33%) in group 2 (p> 0.05). The mean number of procedures required in group 1 was 1.57+/- 0.495 (range: 01-3) and for 2.19 +/ 1.076 (range: 1-5) in group 2 (p<0.05), and mean interval-to-healing was 14.3 months +/- 8.705 (range: 7-36) for group 1 and 12.5 months +/- 7.88 (range: 4-32) for group 2 (p> 0.05). CONCLUSIONS: Bone marrow aspiration injection was better than steroids in treating unicameral bone cyst. PMID- 26878510 TI - Comparison of titanium elastic nails versus Thomas splint traction for treatment of pediatric femur shaft fracture. AB - OBJECTIVE: To compare titanium elastic nails with Thomas splint traction treatment for femur shaft fracture in children. METHODS: The descriptive randomised study was conducted at Abbasi Shaheed Hospital, Karachi, from January 2013 to December 2014, and comprised children aged 6-12 years with simple femur shaft fractures. The patients were randomised into two equal groups. Group A patients were treated with titanium elastic nail and group B patients with Thomas splint traction. Patients were mobilised without weight-bearing on the 5th to 7th postoperative day. In group B, traction was maintained for about 8 to 10 weeks. After splint removal, patients were referred to physical therapy. Patients were available for one-year follow-up. RESULTS: There were 30 patients; 15(50%) in each of the two groups. Those group A had full weight-bearing at 4-6 weeks and early return to routine activities compared to group B patients who took 8-12 weeks. The results were Excellent in 12(80%) patients in group A and 6(40%) patients in group B Postoperative superficial infection occurred in 3(10%) patients. CONCLUSIONS: Titanium elastic nailing is an effective treatment of femur shaft fractures in children. PMID- 26878511 TI - Trends in management of neck of femur fracture. AB - OBJECTIVE: To identify trends related to surgical procedure for the management of neck of femur fracture to see how the choice is changing over time in relation to different age groups. METHODS: The retrospective audit was conducted at Aga Khan University Hospital, Karachi, and comprised data of all patients who presented with neck of femur fracture from 1995 to 2014. Patients with open fractures and those having external fixators were excluded. Data was retrieved from the hospital database, and analysed using SPSS 17. RESULTS: Records of 1039 patients were reviewed. The proportion of patients in the 70+ years age group significantly increased from 45% to 52% over the two decades (p=0.033). Proportion of patients undergoing total hip replacement increased by more than 3 times from 2.6% to 8% (p<0.001).Internal fixation was the most common procedure in patients aged <50 (p<0.001), and hemiarthroplasty for those aged > 50 years (p<0.001). Total hip replacement was seen in its highest proportion (15%) in patients aged 40-49 years (p=0.006). Hemiarthroplasty showed a dramatic decrease in the age group 50-59 years (from 57% to 40%). Total hip replacement showed a steady increasing trend over the last 20 years, most prominently in people in their 50s and 60s (from 1% to 18%; p<0.001). CONCLUSIONS: There is apparently a rising trend in number of patients presenting with neck of femur fracture. Total hip replacement has a rising trend and partial hip arthroplasties have a decreasing trend when it comes to treatment of neck of femur fractures. PMID- 26878512 TI - Assessment with Oswestry disability index in surgically treated patients with lumbar spondylolisthesis: experience in 96 patients. AB - OBJECTIVE: To assess the outcome of surgical treatment in spondylolisthesis of lumbosacral region using Oswestry disability Index. METHODS: The quasi experimental study was conducted at the Combined Military Hospital, Rawalpindi from 2006 to 2013 and comprised surgically treated patients with spondylolisthesis. The patients with degenerative and isthmic types with follow up of at least two years were included. A performa was designed for each patient and records were kept in a custom-built database. Oswestry disability index was used as the assessment tool and assessment was done pre-operatively, at 1, 3 and 6 months and then at 1 year and 2 years. RESULTS: There were 96 patients with mean pre-op Oswestry disability index score of 81.06% (range 42.22-100, SD +/ 11.99). L5-S1 was affected in 44 (45.83%) patients, L4-L5 in 30 (31.25%), L4-5-S1 in 7 (7.29%) and multi or high level was found in the rest of the cases. One level was involved in 77 (80.2%), 2 in 11 (11.45%), 3 in 7 (7.29%) and 4 in 1 (1.04%). The slip grade as per Meyerding grades was 1 in 31 (32.29%), II in 39 (40.62%), III in 19 (19.79%), IV in 5 (5.2%) and 2 (2.08%) had spondyloptosis. Mean follow-up was 42 months (range 24-63). Mean Oswestry disability score at 1 month was 38.51% (range 11- 62.22%, SD +/-11.75); at 6 months 10.02% (range 0 40%, SD +/-6.99); at 1 year 4.62% (range 0-24%, SD +/-5.36) and at 2 years 4.21% (range 0-15%, SD +/-4.2). CONCLUSIONS: Surgical treatment of spondylolisthesis gives excellent long-term result in most patients. PMID- 26878513 TI - Does tranexamic acid reduce blood transfusion following surgery for inter trochanteric fracture? A randomized control trial. AB - OBJECTIVE: To compare the frequency of blood transfusion after surgery for fixation of inter-trochanteric fractures in patients given tranexamic acid versus placebo. METHODS: The randomised control trial was conducted at the Aga khan university hospital from May 1 to October 31, 2014, and comprised patients diagnosed with Inter-trochanteric fracture based on X-ray imaging. The patients were randomised into two equal groups based on a computer-generated random number table. The Intervention group received two doses of 10mg/kg body weight of tranexamic acid just before surgery and three hours later intravenously. The Control group received two doses of 10mg/kg body weight of normal saline at similar intervals. Numbers of blood transfusions required postoperatively were noted based on the postoperative haemoglobin readings. RESULTS: There were 100 patients who were divided into groups of 50(50%) each. Mean post-op haemoglobin for the intervention group was 10.2+/-2.4 g/dl and for the control group it was 8.9+/-2.4 g/dl (p=0.007). Nine (18%) patients in intervention group required blood transfusion compared to 21(42%) in control group (p=0.009). CONCLUSIONS: Administering tranexamic acid was a useful and safe option for reducing requirement of blood transfusion postoperatively after inter-trochanteric hip fractures. PMID- 26878515 TI - Clinical outcome of patients with isolated tibial shaft fractures treated with S.I.G.N interlock nails in terms of surgical site infection and radiological bone healing on follow up. AB - OBJECTIVE: To determine the clinical outcome of patients with isolated tibial shaft fractures treated with Surgical Implant Generation Network interlock nails. METHODS: The observational study was conducted from January 2010 to October 2014 at Allied Hospital, Faisalabad, Pakistan, and comprised in-patient charts. The Surgical Implant Generation Network Fracture Care Online Database was also screened for patients' data to be included in the study. The dependent variables were surgical-site infection and radiographic callus formation (bone healing). Data was analysed using SPSS 17. RESULTS: Out of the 80 patients in the study, 56(70%) were male and 24(30%) were female; the male-to-female ratio being 2.3:1. Overall, 64(80%) patients showed radiographic union and 3(3.75%) patients had surgical-site infection on follow-up after 12 weeks. CONCLUSIONS: The treatment of isolated tibial shaft fractures with Surgical Implant Generation Network interlock nails showed good results in terms of infection and radiographic bone healing. PMID- 26878514 TI - Calcaneal fractures: An audit of radiological outcome. AB - OBJECTIVE: To assess radiological outcome of management of calcaneal fractures. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised data of calcaneal fractures managed between February , 2008 and February, 2014 Cases were identified through medical records, and X-rays were reviewed through digital radiology archive. Bohler?'s angle, Gissane?'s angle, calcaneal height and width were assessed digitally on pre-operative and post-operative X-ray images. RESULTS: Of the27 patients, only 1(3.7%) was female. The cause of fracture was fall from height 15(56%), road traffic accidents 7(26%) and bomb blasts5(19%). Tongue type fractures were 16(59%) and 11(41%) were joint depression type. There was a significant mean increase in Bohler?'s angle (p<0.001) and mean decrease in calcaneal width (p=0.023). Gissane?'s angle and calcaneal height increased marginally (p> 0.05 each). CONCLUSIONS: Measurable improvement in anatomical parameters is possible with surgery, which is a prerequisite for good functional results. PMID- 26878516 TI - Effectiveness of ilizarov frame fixation on functional outcome in aseptic tibial gap non-union. AB - OBJECTIVE: The Objective of the study is to evaluate the effect of Ilizarov frame fixation on functional outcome in aseptic tibial gap non-union cases. METHODS: In this clinical study, 15 cases of post-traumatic aseptic tibial gap non-union were selected in department of orthopedics, Allied Hospital Faisalabad, Punjab Pakistan, during years 2013-2014. After blood analysis and clinical assessment, the aseptic gap nonunion cases underwent ilizarov frame fixation for their problem. They were taught about care of ilizarov fixator and pin tract. They were called on regular basis and pre and post-surgery functional outcome was measured by modified functional evaluation system by Karlstrom-Olerud. RESULTS: Out of the 15 patients, 12 (80%) with road traffic accident, 2 (13.3 %) with gunshot injury and 1(6.66%) with fall from height; 9(60%) were treated by compression technique (fig.1,2,7,8,11), 4(2.66%) with compression-distraction (fig.3,10) and 2 (13.3 %) were treated using distraction-compression technique (bone transport) (fig.4,5,6). Mean gap was 6.33cm (range 2-12cm). Duration of tibial gap union was average 10.60 months (minimum 8 months, maximum 15 months) and union was achieved in all the cases in mean time of 25.20 weeks (minimum 13 weeks, maximum 57 weeks). Patients remained in ilizarov fixator frame for average 6.80 months (range minimum 4, maximum 13 months). Pin tract infection and pain were common Complications. The functional outcome was measured by modified functional evaluation system by Karlstrom-Olerud 5 showed good, 4 satisfactory, 4 moderate and 2 poor results. CONCLUSIONS: The Ilizarov technique is an effective method in treating the aseptic tibial gap non-union. Patient?'s motivation and co-operation played an important role in good to excellent outcomes. PMID- 26878517 TI - Outcome of open reduction internal fixation with cross K-wires for supracondylar fracture of humerus in terms of Flynn's criteria in children. AB - OBJECTIVE: To determine the outcome of open reduction and internal fixation of supracondylar fracture of humerus in children using Flynn?'s criteria. METHODS: The quasi-experimentalstudy was conducted at Punjab Medical College/Allied Hospital, Faisalabad, Pakistan from July 2012 to June 2014and comprised children aged between 5 and 12 years with supracondylar fracture of humerus presenting within one week of the fracture. Post-surgery follow-up included clinical assessment and measurement of carrying angle on radiographs. Outcome was assessed using Flynn?'s criteria. SPSS 17 was used for statistical analysis.. RESULTS: Out of 79 cases, 50(63.3 %) were boys and 29(36.7%) girls. Overall mean age was 7.36+/-1.68 years. Excellent results were obtained in 58(73.4%), good in 14(17.7%), fair in 5(6.4%) and poor in 2(2.5%) patients in terms of functional and cosmetic outcome. CONCLUSIONS: Open reduction and internal fixation of supracondylar fracture was found to be a better choice of treatment with good functional results. PMID- 26878518 TI - Short term evaluation of total hip arthroplasty; our experience at tertiary care center. AB - BACKGROUND: Total hip arthroplasty is a common and successful treatment for osteoarthritis of the hip. Demographic trends in Pakistan suggest a significant increase in the demand for total hip replacement surgery. OBJECTIVES: The current study was planned to assess the outcome of THA at our centre in terms of pain relief and functional improvement by using pre and postoperative HHS. It was observed in this study that the functional outcomes were highly encouraging. Patients were handicapped because of pain, loss of movements and inability to carry out day-to-day activities due to arthritis of the hip joint. The same functional improvements were noted from examination of the patients according to Harris Hip Score. PATIENTS AND METHODS: The descriptive case series was conducted at Punjab Medical College and affiliated hospitals from July 2013 to July 2014, and comprised patients of either gender 25 years or more of age with primary or secondary OA of hip. Severe complications in total hip replacement comprise dislocation, aseptic loosening, infection, peri-prosthetic fracture and limping. Time period of this study was short so a longer period of follow-up is suggested for better evaluation. RESULTS: Mean pre-operative HHS was 31.88+7.43 and post operatively it was 81.23+9.56 which meant good results with marked improvement. CONCLUSIONS: The study concluded that total hip arthroplasty is a secure procedure with tremendous benefits. PMID- 26878520 TI - EDITORIAL. PMID- 26878519 TI - Floating knee injuries: postoperative complications and outcome. AB - OBJECTIVE: To evaluatepost-operative complications and functional outcome of floating knee injuries using Karlstrom?'s criteria. METHODS: The prospective randomised study was conducted at Allied Hospital, Faisalabad, Pakistan, from November 2013 to October2014, and comprised patients of either gender. The injuries were classified using Fraser classification. Femur fractures were treated with intramedullary nails, dynamic hip screws, dynamic condylar screws, dynamic compression plates, buttress plates or external fixators. Tibia fractures were treated with buttress plates, dynamic compression plates, intramedullary nails, inter-fragmentary screws or external fixators.Patients were monitored at 1, 2, 3 and 6 months postoperatively. Final outcome was measured by Karlstrom?'s criteria. RESULTS: Of the 65 patients, 50(77%) were males and 15(23%) were females. According to Fraser classification, there were 46(70.8%)type I, 3(4.6%) type IIa, 7(10.8%) type IIb, and 9(13.8%) type IIc injuries. Most injuries were sustained during motor bike accidents 59(90.8%) involving right limb 38(58.5%) more than the left 27(41.5%), and 22(33.8%) had associated bony injuries and 4(6.2%) had visceral injuries. Non-union occurred in 16(12.3%) fractures, amputation in 5(7.7%), stiffness in 21(32.3%), soft tissue complications requiring reconstruction in 5(7.7%), infection in femur 11(16.9%), and infection in tibia 13(20%). Outcome was Excellent in 16(24.6%), Good 26(40%), Satisfactory 16(24.6%) and Poor 7(10.8%). CONCLUSIONS: A better functional outcome without sequelae/complications depends on the choice of implants according to Fraser classification, comminution at fracture site, intra- or extra-articular nature and whether the fracture is open or closed. PMID- 26878521 TI - K Wire fixation of supra-condylar humerus fractures in children. Is ulnar nerve at risk? AB - OBJECTIVE: To compare iatrogenic ulnar nerve injury in lateral entry pin fixation versus medial and lateral entry pin fixation in the treatment of supracondylar fractures of the humerus in children. Measurement of clinical parameters in terms of elbow range of motion and postop radiographic alignment was also targeted. METHODS: The retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, and comprised data of paediatric patients who underwent closed reduction and percutaneous pin fixation for the treatment of displaced extension type supracondylar fractures of the humerus between July 2007 and June 2012. Data regarding socio-demographic status, disease and procedure variables was collected from patient files and was analysed using SPSS 19. RESULTS: There were 71patients; 37(52%) in the lateral entry group and 34(48%) in the medial and lateral entry group. The two groups were similar in terms of mean age, gender distribution, and preoperative displacement, comminution, and associated vascular and nerve status (p> 0.05 each). There were no cases of iatrogenic ulnar nerve injury in either group and no significant differences between groups with respect to the elbow range of motion and radiological parameters (p> 0.05 each). CONCLUSIONS: With the use of the specific techniques employed, both lateral entry pin fixation and medial and lateral entry pin fixation were effective in the treatment of displaced extension type supracondylar humerus fractures in children. PMID- 26878522 TI - Clinic-based biopsy with a small curette: is it a reliable and safe option in extremity tumours? AB - OBJECTIVE: To establish the diagnostic accuracy and safety of clinic-based biopsy done with a small curette. METHODS: The retrospective study was conducted at Aga Khan University Hospital Karachi and comprised data of patients who underwent biopsy procedure of extremity tumours in clinic under local anaesthesia from July 2009 to June 2012. Patients who underwent the procedure in operating room under general anaesthesia were excluded and so were those with insufficient or missing information, or those who had the final procedure done elsewhere. Clinical parameters were evaluated and histo-pathology was compared with the final resected specimen. RESULTS: The mean age of the 51 patients in the study was 32+/ 19.6 years. Lower extremity was involved in 37(73%) cases, and the most common tumour was osteosarcoma in 9(17%).Biopsy was inconclusive in 2(4%) patients, leaving the clinical accuracy to be 94%. The cost of clinic-based biopsy was at least seven times less than those done in the operating room under general anaesthesia. CONCLUSIONS: Biopsy done in a clinic with a small curette is accurate, safe and cost-effective method. PMID- 26878523 TI - Clinic based biopsy vs. theatre biopsy of bone and soft tissue extremity tumours: comparable diagnostic modalities. AB - OBJECTIVE: To compare the diagnostic accuracy of clinic-based biopsy versus theatre biopsy against final histopathology in patients presenting with extremity tumours. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised record of patients who underwent biopsy procedure of extremity tumours from January 2008 to December 2011. Data regarding socio-demographic status, disease-related and procedure-related variables were collected from the files. Histopathology report of biopsy was compared with the final histopathology after definite procedure of the tumour for concordance. RESULTS: Of the 87 patients whose records were reviewed, 42(48%) had undergone biopsy in theatre and 45(52%) in clinic. The overall median age was 29 years (Inter-quartile range: 18-58 years). As compared to final histopathology after the definite procedure, diagnostic accuracy of theatre and clinic-based biopsy was 97.7% vs. 95.5% respectively. Surgical site infection was observed in 2(5%) in theatre and in 1(2.2%) in clinic. CONCLUSIONS: Clinic-based biopsy was accurate and safe with diagnostic accuracy comparable to theatre-based biopsy. Clinic-based biopsy, being cost-efficient along with low morbidity, should be preferred in patients with extremity tumours. PMID- 26878524 TI - Do delays in surgery affect outcomes in patients with inter-trochanteric fractures? AB - OBJECTIVE: To study the differences in outcomes of early versus delayed surgery in patients with intertrochanteric fractures. METHODS: The retrospective chart review was conducted at Aga Khan University Hospital, Karachi, and comprised data of patients who underwent surgery for intertrochanteric hip fractures from 2005 to 2010. A gap of >48hours between the event and the surgery was considered a delayed procedure and its impact on outcome was assessed. RESULTS: Of the 190 patients, 138(72.6%) were in the early group and 52(27.3%) in the delayed group. The most common cause for delay of surgery was electrolyte imbalance in 14(27%) patients. Patients with delayed surgery had more comorbidites and higher ASA grades compared to those that underwent early surgery (p<0.05). Inpatient mortality was significantly higher in the delayed group (p=0.006). Multivariate analysis showed that higher mortality was associated with delay in surgery. CONCLUSIONS: In patients with multiple comorbid conditions, expedited optimisation for surgery may be warranted to reduce mortality. PMID- 26878525 TI - Efficacy of tranexamic acid in reducing blood loss in total knee replacements. AB - OBJECTIVE: To assess the efficacy of tranexamic acid in reducing blood loss in total knee replacement. METHODS: The retrospective study was conducted at Quaid-e Azam International Hospital, Islamabad, Pakistan, and comprised data of patients who underwent total knee replacement between January 2012 and December 2014. The effect of tranexamic acid on postoperative haemoglobin, hematocrit and number of blood units transfused was noted and compared between cases who had received standard dose of tranexamic acid with those who had not received it. SPSS 19 was used for data analysis. RESULTS: A total of 416 knee replacement surgeries were conducted during the study period and involved 254 patients; 76(30%) men and 178(70%) women. The overall mean age was 62.2+/-9.6 years (range: 36-87 years). Tranexamic acid was used in 162(74%) patients and was not used in 92(36%). When it was used, only 26(16%) patients required blood transfusion, but when it was not used, 35(39.1%) required transfusion (p<0.05). CONCLUSIONS: Tranexamic acid was able to reduce total blood loss and transfusion requirements. PMID- 26878526 TI - Postoperative range of motion and stability after anterior cruciate ligament reconstruction using quadrupled hamstring autograft. AB - BACKGROUND: The incidence of anterior cruciate ligament (ACL) tear is increasing, especially in young active adults. Various surgical options like bone-patellar tendon-bone graft and hamstring autograft have been the focus of evaluation and comparison in various aspects, each having specific advantages and demerits. We are increasingly using and analysing quadrupled hamstring autograft for ACL reconstruction. Previously it was advocated as a sports injury, but now we note that road traffic accidents (RTAs) are the most common cause of ACL tear. OBJECTIVE: Objective of this study was to evaluate clinical results of ACL reconstruction in terms of stability and range of motion using hamstring autograft. MATERIALS AND METHODS: We enrolled 50 patients from June 2011 to May 2014with isolated ACL rupture, used autologous quadrupled hamstring graft and compared the clinical improvement of knee stability and range of motion preoperatively versus postoperatively using pivot shift test and lachman test. Every patient underwent a standardised 6-month rehab follow-up plan and then findings were documented and analysed using SPSS 17. RESULTS: Marked improvement was seen at 6-month follow-up. Preoperatively 44(88%) patients showed grade 2 positive pivot shift test while postoperatively only 1(2%) showed grade2 positive pivot shift,and 47(94%) patients improved to grade0 pivot shift. Similarly,44(84%) patients were having grade 2 positive lachman test preoperatively which improved to43(86%), showing grade0 lachman test and only 5(10%) showed grade2 positive lachman test. PMID- 26878527 TI - Factors affecting functional outcome after lower extremity amputation. AB - BACKGROUND: More than 100,000 major lower extremity amputations -- amputations at the metatarsal, below-knee or above-knee level -- are performed yearly in the United States. Despite improvements in long-term outcome, operative mortality following such amputations has remained stable at 9% to 10% over the last 20 years. Several predictors for functional outcome of amputee patients are mentioned in the literature. OBJECTIVES: The current study was planned to assess the impact of comorbidities on functional status after lower extremity amputations. MATERIALS AND METHODS: It was a prospective comparative study held at the Department of Orthopaedics and Traumatology, Punjab Medical College, Faisalabad, and affiliated hospitals. The study included 104 patients regardless of age and gender. Patients were allocated into trans-metatarsal (TM) group, below-knee (BK) amputation group and above-knee (AK) amputation group. Comorbidities before amputation included diabetes mellitus (70.7%), coronary heart disease (57.1%), chronic kidney disease (53.6%), and/or congestive heart failure (52.1%). RESULTS: Mortality within 30 days of hospital discharge was 9%, and hospital readmission was 27.7%. Stroke, end-stage renal disease (ESRD) and poor baseline cognitive function were associated with the poorest functional outcome after amputation. Patients undergoing BK or AK amputation failed to return to their functional baseline within 6 months. CONCLUSIONS: Higher amputation level, history of stroke, ESRD, poor baseline cognitive scores, and female gender are factors associated with inferior functional status after amputation. PMID- 26878528 TI - Functional outcome following olecranon osteotomy approach for fixation of T/Y fractures of distal humerus. AB - OBJECTIVE: To evaluate the functional outcome of fixation of T/Y fracture distal humerus through olecranon osteotomy. STUDY DESIGN: Quasi experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Jinnah Postgraduate Medical Centre, Karachi from June 2011 to December 2011. METHODOLOGY: Patients of either sex presenting with T/Y(configuration) fracture Humerus of Risenborough Radin type II-IV and less than three weeks duration were included. Diagnosis was made by X-rays and underwent fixation by posterior approach through olecranon osteotomy. Functional outcome was measured by using Risenborough-Radin criteria of range of motion as good, fair and poor. The data was analyzed using SPSS version 13. RESULTS: 71 patients aged between 20-50 years were enrolled. Mean duration of trauma was 12.2+/-4.4 days. Majority 55 (77.5%) had type III fracture. Patients less than 40 years had good outcome in 52.8% cases and fair outcome in 41.7% cases better than patients more than 40 years age. In females, outcome was 68.8% which was better than males. Trauma of less than 12 days of duration had good outcome in 60.5% of cases. Type II fracture had better outcome than other types. Overall, 39 patients (54.9%) had good outcome, fair outcome in (33.80%) 24 patients and poor outcome in (11.27%) 8 patients. CONCLUSIONS: Posterior approach using Transolecranon osteotomy is a satisfactory procedure for fixation of T/Y fracture of distal humerus, because it achieves good functional outcome post operatively in terms of range of motion of elbow compared to other procedures. PMID- 26878529 TI - A comparative review of three techniques of syndactyly release. AB - OBJECTIVE: To compare the outcome of three techniques of congenital syndactyly release; to identify factors leading to difference in outcome, and to identify the incidence of neurovascular abnormalities in various types of syndactyly. METHODS: The chart review was conducted at The Indus Hospital, Karachi, and comprised data of all patients who had undergone syndactyly release between August 2008 and December 2014. Three techniques of release were included as described in literature by Bauer, Skoog and Niranjan. The data was collected through Health Management Information System. A detailed questionnaire was designed to address variables of interest. RESULTS: The age of the 29 patients with 50 webs in the study ranged from 2.2 to 17.1 years. The male to female ratio was 21:8. The complications encountered were web creep, skin flap necrosis, flexion deformity and contracture of joint. Single neurovascular bundle was found in 04(8%)webs and 45(90%) required skin graft for resurfacing of the digits. CONCLUSIONS: Bauer technique was found to be to be superior for web formation and there was low incidence of web creep compared to Skoog technique. Inclusion of syndromic cases may lead to increased complication and dissatisfaction rate. Tight closure of flaps should be avoided and generous use of skin grafts is advocated for success. PMID- 26878530 TI - Glomus tumours: Outcome based on tumour location in hand. AB - OBJECTIVE: To determine the clinical outcome of patients with glomus tumour in nail matrix and nail bed that were excised with transungual approach. METHODS: The case series was conducted at the Allied and District Headquarter Hospital, Faisalabad, Pakistan,from January 2012 to June 2014, and comprised patients with glomus tumour at finger tipswhose diagnosis was confirmed with biopsy results. Variables noted were the location of the tumour in the nail i.e. either nail matrix or the nail bed. RESULTS: Of the 8 patients in the study, 5(62.5%) had tumours located in the nail matrix and 3(37.5%) in the nail bed. Three (60%) patients with nail matrix tumour had prolonged pain sensation, whereas none (with nail bed lesion had prolonged pain sensation. CONCLUSIONS: There was no recurrence but anatomic location of the subungual glomus tumour at initial presentation can predict postoperative prolonged pain. PMID- 26878531 TI - Effect of continuous passive motion on knee flexion range of motion after total knee arthroplasty. AB - OBJECTIVE: To compare mean knee flexion in patients on continuous passive motion and those without it after total knee arthroplasty. METHODS: The randomised controlled study was conducted at Aga Khan University Hospital, from July 2013 to June 2014, and comprised patients who underwent total knee arthroplasty. Patients were randomly assigned to either group, with Group A receiving standardised physiotherapy from 1st postoperative day, and Group B receiving physiotherapy and one hour of continuous passive motion twice a day from 1st postoperative day until discharge. Outcome assessment was done on the day of discharge. RESULTS: Of the 76 patients, there were 38(50%) in each group. There were 61(80%) women and 15(20%) men, with a mean age of 65.5+/-7.9 years in Group A and 61.6+/-9.1 years in Group B. The mean preoperative knee flexion in Group A was 90.3+/-13.2 degrees and in Group B it was 96.9+/-11.5 degrees . Mean maximum flexion at the time of discharge was 96.3+/-5.7 degrees in Group A and 94.3+/-8.4 degrees in Group B (p=0.22). The mean length of stay in Group A was 6.1+/-1.4 days and in Group B it was 8.6+/-2.4 days (p=0.01). CONCLUSIONS: Continuous passive motion had no influence on knee range of motion after total knee arthroplasty at the time of discharge. PMID- 26878532 TI - The pulley suture: A reliable option for closure of selected soft tissue defects under tension- three years experience of a tertiary care hospital. AB - OBJECTIVE: To assess the outcome of closure of soft tissue defects through pulley suture in different clinical situations. METHODS: The descriptive chart review was conducted at The Indus Hospital, Karachi, and comprised data from May 2008 to November 2011. A detailed questionnaire was developed to address variables of interest. All patients with less than three months of follow-up or inadequate information were excluded. The data was collected through Health Management Information System. Data was entered and analysed by SPSS 16. RESULTS: There were 259 patients with 289 wounds in the study. The mean age was 29.2+/-11.9 years. At follow-up of two weeks, there was wound dehiscence in 2.07%, infection in 0.69% and partial flap necrosis in 1.03% patients. At 12 weeks, hypertrophic scar was reported in 2.07% and stretched scar in 0.3% patients. Acute pain was not reported in the first week of surgery. Type of wound was found to have significant association with complications (p value<0.005). Age and gender were not found have any significant association with complications (p value 0.372 and 0.238 respectively). None of the patients reported scar tenderness at 12-week follow-up. Cosmetic outcome was acceptable to all patients. CONCLUSIONS: Judicious use of pulley suture can lead to primary closure of selected soft tissue defects under moderate tension. The technique, however, needs to be utilised by surgeons experienced in soft tissue reconstruction. PMID- 26878533 TI - Protection of heel flaps with Ilizarov fixator as an elevation frame: A case series and review of literature. AB - OBJECTIVE: To compare outcome of Ilizarov fixator for protection of heel and foot flaps with that of plaster of Paris boot technique. METHODS: The retrospective chart review was conducted at The Indus Hospital, Karachi, and comprised data of patients who underwent flap reconstruction of the heel from January 2011 to December 2014. All patients had a minimum follow-up of 3 months. The patients using Ilizarov fixator were placed in group A and those with modified plaster of Paris boot as the elevation device were placed in group B. A detailed questionnaire was developed to note down the relevant variables. RESULTS: Of the 31 patients, 21(70%) were in group A and 10(30%) in group B. The modified boot was considered heavy (70%) compared to none in the Ilizarov group. The mean time of removal was 5.9 wks in group A and 4.8 weeks in group B. The mean time for use of Foley?'s catheter was 16.8 hours in group A and 14.8 hours in group B. There was significant number of associated bony injuries (33%) in group A and none in group B. Both groups were satisfied with the outcome. CONCLUSIONS: While Ilizarov technique is recommended for patients with extensive wounds along the heel and foot, obese patients and those non-compliant to the positioning protocol, careful use of modified plaster of Paris boot technique in relatively simpler situations of heel reconstruction with flaps is also very rewarding. PMID- 26878535 TI - Clinical outcome of cemented bipolar hemiarthoplasty versus Austin Moore hemiarthroplasty for displaced intracapsular fractures of hip in terms of anterior thigh pain in elderly. AB - OBJECTIVE: To explore a less pain-inciting implant in terms of anterior thigh pain after hip hemi-arthroplasty in displaced intra-capsular fractures of the neck of femur. METHODS: The cross-sectional comparative study was conducted at the Combined Military Hospital, Rawalpindi, from November 2013 to June 2014, and comprised patients of either genders with age above 55 years and having displaced intra-capsular fractures of the neck of femur. The patients were divided into two equal groups, with Group A patients undergoing Austin Moore hemi-arthoplasty and Group B having cemented bipolar hemi-arthoplasty. Follow-up was done at 4, 8 and 12 weeks postoperatively for anterior thigh pain on the basis of visual analogue scale. Mean pain scores for both groups were calculated and compared. RESULTS: There were 60 patients; 30(50%) in each group. The mean age in Group A was 78.40+/-6.95 years, while in Group B it was 77.16+/-6.32. The overall male-to female ratio was 1.8:1. All patients had uneventful postoperative recovery. Mean anterior thigh pain in Group A was statistically higher than Group B (p<0.05). CONCLUSIONS: Compared to Austin Moore hemi-arthoplasty, cemented bipolar hemi arthoplasty caused significantly lower incidence of anterior thigh pain. PMID- 26878534 TI - Early experience of dynamic hip screw with spiral blade and locking side plate for the stabilization of trochanteric fractures. AB - OBJECTIVE: To evaluate early experience with helical hip system in osteoporotic elderly patients with per-trochanteric fractures. METHODS: The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised records of patients having low-velocity pertrochanteric fractures who were fixed with spiral blade Dynamic Helical Hip Systemfrom July to December 2014 and were followed up for a minimum of 3 months. Demographic variables and clinical outcomes were noted from the medical records whereas operative details were recorded from the operative note. Radiological variables and outcomes were assessed by viewing appropriate pre-operative, post-operative and follow-up radiographs. RESULTS: Of the 32 patients in the study, 14(44%) were men and 18(56%) were women, with an overall mean age of 77.81+/-7.04 years and mean body mass index of 25.99+/-4.13 kg/m2. Of the total, 1(3.13%) patient had implant cut out, 1(3.13%) had myocardial infarctionand 2(6.2) expired. CONCLUSIONS: The introduction of spiral blade dynamic hip screw manifested favourable results and good clinical and radiological outcomes with low cut-out rates. PMID- 26878536 TI - OSATS for total knee replacement: Assessment of surgical competence in the operating room. AB - Traditionally the surgical and technical competence of Residents has been assessed inadequately and has received little attention among the core competencies defined by the Royal College of Physicians and Surgeons of Canada?'s CanMEDS programme and the Accreditation Council for Graduate Medical Education (ACGME). With the development of novel and advanced surgical techniques with different learning curves, time pressure in busy operating rooms, and increasing complexity of cases at university hospitals, acquiring technical skills for Residents has become more challenging. Over the last two decades, methods have been developed to assess technical competence objectively. In this paper we describe use of an Objective Structured Assessment of Technical Skills (OSATS) for total knee replacement (TKR). PMID- 26878537 TI - Hip fragility fractures: Anaemia, calcium and vitamin D supplementation. AB - OBJECTIVE: To assess the burden of anaemia and osteoporosis in hip fracture patients, to determine the rate of blood transfusion per-operatively, to assess the use of calcium and vitamin D supplements and the use of anti-osteoporotic medications postoperatively. METHODS: A retrospective study was conducted at Aga Khan University and Hospital (AKUH) between June 2009 and May 2011, and comprised record of patients treated for intertrochanteric and femur neck fractures. Patients with associated pathological, open or long bone fractures were excluded. The main study outcome measures were the use of pre-operative and post-operative calcium, vitamin D, bisphosphonates and management of anaemia pre- and post operatively. Demographic data was also collected including age, gender, and co morbids. Statistical analysis was performed using SPSS 19. RESULTS: Of the 129 patients, 65(50.4%) were women. The overall mean age was 67.2+/-15.5 years. Mean pre-operative haemoglobin level was 12.3+/-1.5 gm/dl and 39(30%) patients were anaemic, while post-operative haemoglobin was 10.2+/-1.71 with 90(70%) anaemic patients, but only 14(10.9%) patients received per-operative blood transfusion. Pre-operative and post-operative vitamin D supplementation was advised in 3(2.3%) and 18(14%) patients respectively, whereas pre-operative and post-operative bisphosphonate supplementation was advised in 3(2.3%) and 1(0.8%) patients. CONCLUSIONS: There is a strong need to pay attention to the management of peri operative anaemia and calcium, vitamin D and bisphosphonate supplementation in the discharge medications of patients with hip fragility fractures. PMID- 26878538 TI - Intertrochanteric hip fractures in octogenarian patients: Do we need to rethink fixation strategy? AB - OBJECTIVE: To compare outcomes in octogenarians with younger patients up to 1 year after undergoing dynamic hip screw fixation for intertrochanteric fractures to see the effectiveness of the implant. METHODS: The retrospective case-control study was conducted at The Aga Khan University and comprised records of patients who underwent dynamic hip screw surgery between January 1, 2010, and December 31, 2012. They were divided into two groups based on their age:. Group A <80 years; and Group B > 80 years. All patients had a one-year follow-up> Data including mortality, morbidity, radiological healing time, postoperative ambulatory status and Harris hip score were recorded. RESULTS: Of the 150 patients, 114(76%) were in Group A and 36(24%) were in Group B. Up to 25(70%) of octagenarians dropped their ambulatory ability by one or two levels, whereas 107(94%) of Group A patients were able to either maintain their pre-injury ambulatory ability or dropped their ambulation by one level only (p=0.02). Postoperative complications were higher in Group B 9(25%) compared to Group A 4(4%). One-year mortality was also significantly higher in Group B 8(22%) compared to Group A 9(8%) (p=0.03). CONCLUSIONS: Octagenarians undergoing internal fixation with dynamic hip screw had higher frequency of complications and death compared to younger patients. PMID- 26878539 TI - Improvement in Harris Hip Score after cementless total hip arthroplasty in young active adults with secondary hip arthritis- A short-term follow-up result. AB - OBJECTIVE: To determine the improvement in Harris Hip Score after non-cemented total hip replacement in younger patients with secondary hip joint arthritis. METHODS: The quasi-experimental study was conducted at Unit I, Department of Orthopaedic Surgery and Traumatology, Mayo Hospital, Lahore, and comprised patients diagnosed clinically and radiologically as secondary hip joint arthritis from September 2009 to December 2014. Harris Hip Score was calculated pre operatively. All patients were operated by the same surgical team. One dose of second-generation intravenous cephalosporin after test dose was given at induction of anaesthesia followed by 3 times daily postoperatively along with aminoglycosides twice daily for three days followed by oral quinolones for 2 weeks. Patients were followed up for 6 months. The improvement in hip score was classified as poor, fair, good and excellent. Data entry and analysis was done using SPSS 11.5. RESULTS: Of the 65 patients in the study, 43(66%) were male and 22(34%) were females. Right hip was involved in 40(62%) patients and 25(38%) had pathology in the left hip. Overall mean age of male and female patients was 35.69+/-5.55 years and 35.72+/-5.95 years respectively. Harris Hip score improved over 6 months from poor to fair. CONCLUSIONS: The use of non-cemented total hip arthroplasty conferred a significant improvement in function in young patients with arthritis of the hip joint. PMID- 26878540 TI - Giant cell tumour of foot bones - 25 years experience in a tertiary care hospital. AB - OBJECTIVE: To determine the incidence of giant cell tumour in foot, its clinical features, stage of tumour, treatment and outcome of surgery. METHODS: This retrospective case series study was conducted at Jinnah Postgraduate Medical Centre, Karachi, and comprised cases of giant cell tumour of foot bones diagnosed between January 1990 and March 2015. Tumour Incidence, type of procedure and results were recorded on a proforma and analysed for function outcome and recurrence. Clinical and radiological follow-up was done for a maximum 6 years. RESULTS: There were 240 cases of giant cell tumour but only 13(5.4%) related to foot bones. Of them, 8 (3.3%) were females and 5(2.0%) males. The mean age was 25 years (SD 10.59) (range: 17-38 years). In 7 (2.9%) cases lesion was in metatarsals, 2(0.8%) cases in phalanges, 3(1.2%) cases in calcaneus and 1(0.4%) case in talus. Duration of symptoms ranged from 4 to 12 months. All presented with radiologically stage 2 or 3 lesions. Resection of tumour and reconstruction with fibular graft was performed in 5(2.0%) cases, excision/curettage and filling cavity with cancellous bone graft in 5(2.0%) cases, resection in 2(0.8%) cases and toe amputation in 1(0.4%) case. There was recurrence in 2(0.4%) cases. No other complication was noted on last follow-up. CONCLUSIONS: Giant cell tumour in foot bones is a rare tumour and shows specific clinical and radiographic features with early involvement of entire bones, more aggressive behaviour with recurrence potential. The preferred treatment options are resection with reconstruction, curettage and filling cavity with bone graft/cement and amputation. PMID- 26878541 TI - Outcome of surgical treatment of cervical spondylotic myelopathy: Experience in 120 patients. AB - OBJECTIVES: To document the outcome of spinal surgery in patients of cervical spondylotic myelopathy. METHODS: The quasi-experimental study was conducted at the Department of Spine Surgery at Combined Military in a tertiary care hospital in Rawalpindi from 2006 to 2013. A pre-designed proforma was used for each patient and records were kept a custom-built computer database. Neurik grading was used to assess neurological status preoperatively, at 6 months, 1 year and 2 years. RESULTS: There were 120 patients with a mean age of 60.08 years (range 26 82, standard deviation 13.13). Of them 108 (90%) were males and 12 (10%) females. The preoperative neurologic status was Nurick?'s grade 0 in 6 (5%) patients There were 120, I in 9 (7.5%), II in 23 (19.16%), III in 28 (23.33%) and IV in 19 (15.83%) and V in 35 (28.16%). The spine was approached anteriorly in 48 (40%) patients and posteriorly in 72 (60%). Single level was involved in 23 (19.16), two in 30 (25%), three in 22 (18.33%) and four in 45 (37.5%) cases. Anterior cervical disc excision and fusion was done in 26 (21.67%), anterior corpectomy and fusion with bone graft or a cage in 21(17.5%) cases, laminoplasty in 9 (7.5%), laminectomy with lateral mass screw fixation with reconstruction titanium plate in 37 (30.83%) or with rod 24 (20%). In 3 (2.5%) cases only decompressive laminectomy was done. At 6 months Nurick 0 was in 26 %21.67%), I in 14 (11.67), II in 17 (14.16), III in 21 (17.5), IV in 29 (24.16%) and V in 13 (10.83). At one year Nurick grade was 0 in 38 (32.67%, I in 16 (13.33%), II in 14 (11.67), III in 15 (12.5%), IV in 23 (19.16) and V in 14 (11.67%). At the end of 2 years Neurik grade was 0 in 40 (33.33%), I in 15 (12.5%), II in 13 (10.83%), III in 16 (13.33%), IV in 22 (18.33% and V in 14 (11.67%). CONCLUSIONS: Single, double and triple levels with predominantly anterior cervical spondylotic myelopathy pathology can be operated anteriorly while multi-level disease with lordotic spine should be approached posteriorly. PMID- 26878542 TI - Early release of tourniquet in total knee arthroplasty: Is it worthwhile? AB - OBJECTIVE: To compare the effects of duration and timing of tourniquet release on perioperative blood loss, transfusion requirement, duration of surgery, length of hospital stay and early complications in total knee arthroplastywith and without additional anti-fibrinolytic therapy. METHODS: The prospective quasi-experimental study was conducted at the Combined Military Hospital, Rawalpindi, from March to August 2014. The patients undergoing total knee arthroplasty were divided into two groups: in Group A tourniquet was released after closure of surgical wound and applying compressive dressing; and in Group-B tourniquet was deflated after cementation of implants following which closure was done. Each group was further divided into those who received tranexamic acid (A-T, B-T) and those who did not (A-C, B-C). Study variables were noted on a proforma and analysed. RESULTS: Of the 75 patients in the study, 27(36%) were male and 48(64%) were females. Calculated blood loss was 408mL and 422mL in group A-T and B-T respectively (p=0.73), and 615mL and 610mL in group A-C and B-C respectively (p=0.95). Tourniquet time was significantly shorter (p<0.0005) in group B whereas duration of surgery was significantly shorter (p<0.0001) in group A (68+/-9min vs 77+/ 11min). Transfusion frequency was higher in group B. Complication rate in the two main groups was not significantly different (p=0.314). Mean length of hospital stay was not significantly different (p>0.05). CONCLUSIONS: Earlier intra operative release of tourniquet in patients undergoing total knee arthroplasty was associated with increased surgery time and higher frequency of blood transfusion without conferring any significant benefit. PMID- 26878543 TI - New technique: tendon interposition arthroplasty in Distal Interphalangeal Joint arthritis in Chinese population - New horizon for treatment. AB - OBJECTIVE: To evaluate the clinical outcome of managing distal inter-phalangeal joint arthritis by using excisional arthroplasties with soft-tissue interposition to provide pain-free joint with adequate range of motion and preserving the bone stock. METHODS: The case series was conducted at Queen Mary Hospital, Hong Kong from 2013 to 2015 and comprised patients with distal inter-phalangeal joint arthritis. Excisional arthroplasty was performed for all patients. Interposition was performed using extensor retinaculum/ palmaris longus. An axial K wire for 3 4 weeks was applied to maintain the reconstructed part in satisfactory alignment. Mallet splint was applied for another 3 weeks. Free active mobilisation was allowed afterward. Clinical assessment was done at least at 3, 6 and 12 months. RESULTS: There were three patients in the series, and all the 5 fingers, including one thumb, achieved good range of motion with no complication except in 1(33.3%) patient who needed re-exploration of index finger for retained suture with no documentary infection. All patients (100%) had significant pain relieved with mean visual analogue scale score of 3/10+/-SD at 3 months and 0/10 at 1-year follow-up. All achieved good range of motion. All (100%) were satisfied with postoperative surgical outcome. CONCLUSIONS: Interposition arthroplasty gave the patients adequate range of motion with preservation of bone stock. PMID- 26878544 TI - Less invasive versus standard total knee replacement: Comparison of early outcome. AB - OBJECTIVE: To compare less invasive quads conserving (limited parapatellar) approach with standard medial parapatellar approach with respect to early functional outcome in cases of total knee arthroplasty. METHODS: The retrospective case-control cohort study comprised cases operated upon between June 2009 and March 2012 in Combined Military Hospitals in Pakistan by a single surgeon. Data related to osteoarthritis patients who underwent unilateral primary total knee replacement were included. They were divided into two equal groups of control who had standard total knee arthroplasty, and the test group where less invasive surgery method was employed. Patients were followed up for 3 months postoperatively. The outcomes recorded included mean hospital stay, time to assisted ambulation, time to independent ambulation, mean range of motion and Knee Society Scores [KSS] 1 and 3 months postoperatively. RESULTS: There were 120 subjects with 60(50%) in each of the two groups. Mean hospital stay was 3.2+/-0.6 days for the test group compared to 5.8+/-1.6 days for the control group. Most test group patients were walking with assistance on 2nd postoperative day (mean: 1.7+/-0.6 days), whereas control group on the 4th day (mean: 4.1+/-1.1 days). Independent ambulation was seen at 2.1+/-0.3 weeks and 4.0+/-0.7weeks respectively in the two groups. Postoperative range of motion at 1 month was 118+/-13 for patients in the test group, and 99+/-13 for control group, with Knee Society Scores of 87+/-6 and 72+/-9 respectively. The difference in all results was statistically significant (p<0.05). CONCLUSIONS: Less invasive surgery for total knee arthroplasty was associated with faster recovery, earlier assisted and independent ambulation, shorter lengths of hospitalisation and better Knee Society Scores at 1and 3months postoperatively. PMID- 26878545 TI - Prophylaxis against heterotopic ossification after elbow and acetabular fractures - Do we really need it. AB - OBJECTIVE: To compare the efficacy and safety of prophylactic modalities for heterotopic ossification prevention after elbow and acetabular surgeries. METHODS: The retrospective chart review was conducted at the Aga Khan University Hospital and comprised record of patients who underwent open reduction and internal fixation for elbow and acetabular fractures between 2010 and 2013. Data was classified into three groups: Group A patients had received single dose of radiotherapy; Group B patients had received indomethacin, and Group C patients had not received any prophylaxis. Outcome variables included time-to-fracture healing, heterotopic ossification, non-union and wound infection. RESULTS: Of the 104patients 70(67.3%) had elbow fractures and 34(32.7%) had acetabular fractures. Out of the 70patients with elbow fractures, 28(27%) were in Group A, 24(23%) in Group B, and 18(17%) in Group C. In Group A, 4(22%) patients had wound infection compared to 1(5.5%) patient in Group C (p=0.131). One (4%) patient in Group B and 1(5.5%) in Group C developed heterotopic ossification (p=0.486). Non-union occurred in 1(4%) patient in Group B and 1(5.5%) in Group C. Out of the 34 patients with acetabular fractures, 11(32.3%) were in Group A, 10(29.4%) in Group B, and 13(38.2%) in Group C. In Group A, 2(18.2%) patients developed wound infection. Only 1(7.6%) patient in Group C developed heterotopic ossification. CONCLUSIONS: No role of radiotherapy or indomethacin was detected in the prevention of heterotopic ossification. PMID- 26878546 TI - Single stage bilateral total hip replacement: Is it an option or a risk? AB - OBJECTIVE: To evaluate safety and feasibility of two-stage total hip arthroplasty and to compare it with single-stage procedure. METHODS: The retrospective study was conducted at The Aga Khan University Hospital and comprised all cases of total hip replacements between January 2001 and December 2014 that were retrieved from the database using International Classification of Diseases (9th Revision) coding. A standardised questionnaire was completed, including patient demographics, primary diagnosis, peri and postoperative morbidity and mortality. Differences among patients?' data were analysed using chi square test for dichotomous variables and student t-test for continuous variables. RESULTS: Of the 48 cases, 34(71%) had single-stage bilateral total hip replacement and 14(29%) had two-stage procedure. The mean hospital stay in the single-stage group was 8.1+/-3.2 days compared to 19.6+/-5 days in the other group. The two-stage group required a significantly greater need for transfusion compared to the single-stage group (P<0.05). There was no statistically significant increase in peri or postoperative complication (p> 0.05). CONCLUSIONS: Simultaneous bilateral total hip arthroplasty was found to be a safe and viable option with a decreased transfusion requirement and shorter hospital stay along with no significant increase in morbidity or mortality. PMID- 26878547 TI - Outcome of ilizarov fixator in tibial non-union. AB - OBJECTIVE: To evaluate the results of non-union of tibia treated with Ilizarov fixator. METHODS: The case series was conducted at Hayatabad Medical Complex, Peshawar, from January 2012 to April 2015, and comprised consecutive patients with non-union of the tibia. Patients of either gender, with complex non-union of the tibia from the age of 18 to 65 years were included, while patients with intra articular fractures, vascular injury, smokers and steroid users were excluded. Outcome of the treatment was graded by using the scoring system of Association for the Study and Application of Methods of Ilizarov. RESULTS: There were 21 patients with a mean age of 40+/-13.89 years (range: 18-65 years). There were 7(33.3%) female and 14(66.6%) male patients. There were 14(66.6%) patients who had one previous surgery, 5(23.8%) had 2 surgeries and 2(9.5%) had 3. Bone results were excellent in 12(57.1%) patients, good in 6(28.6%) and fair in 3(14.3%). Functional results were excellent in 7(33.3%) patients, good in 9(42.9%), fair in 4(19%) and poor in 1(4.8%). CONCLUSIONS: Ilizarov fixator gave good to excellent results in tibialnon-union, by eradicating the infection, filling the defect with bone transport, correcting the deformity and the limb length discrepancy. PMID- 26878548 TI - Evaluation of the Edwards SAPIEN 3 Transcatheter Valve For Aortic Stenosis. AB - Transcatheter aortic valve replacement is a viable alternative to surgical aortic valve replacement in patients with severe aortic stenosis. The SAPIEN 3 is the latest generation of balloon-expandable transcatheter heart valve, designed to address some of the shortcomings of earlier versions of transcatheter heart valves. It has a lower device profile to reduce access-related vascular injury, an improved delivery catheter to facilitate accurate implantation, and incorporates an additional outer sealing cuff to minimize paravalvular leakage. The latest European and North American trials using SAPIEN 3 have documented very low rates of vascular complications and paravalvular regurgitation with rates of stroke and mortality rates lower than anticipated with SAVR in both intermediate and high surgical risk patients. PMID- 26878550 TI - YihQ is a sulfoquinovosidase that cleaves sulfoquinovosyl diacylglyceride sulfolipids. AB - Sulfoquinovose is produced by photosynthetic organisms at a rate of 10(10) tons per annum and is degraded by bacteria as a source of carbon and sulfur. We have identified Escherichia coli YihQ as the first dedicated sulfoquinovosidase and the gateway enzyme to sulfoglycolytic pathways. Structural and mutagenesis studies unveiled the sequence signatures for binding the distinguishing sulfonate residue and revealed that sulfoquinovoside degradation is widespread across the tree of life. PMID- 26878551 TI - Allostery: A lipid two-step. PMID- 26878553 TI - Exercise intervention for the treatment of trismus in head and neck cancer - a prospective two-year follow-up study. AB - Background This study aims to investigate the long-term effects of structured trismus intervention in patients with head and neck cancer (HNC) and trismus in terms of mouth opening, trismus-related symptoms and health-related quality of life (HRQL). Material and methods Fifty patients with HNC to receive radiotherapy +/- chemotherapy were included in this prospective study along with a matched control group. The intervention group received a 10-week structured exercise with a jaw mobilizing device (TheraBite(r) jaw device or Engstrom device). Patients were assessed before and after trismus exercise intervention and at a two-year follow-up. Primary endpoint was maximum interincisal opening (MIO) and secondary endpoints included trismus-related symptoms and HRQL assessed with patient reported outcome (PRO)-instruments [Gothenburg Trismus Questionnaire (GTQ), European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30) and the related HNC-specific module the EORTC Head & Neck Questionnaire (EORTC QLQ-H&N35)]. Results The intervention group had a higher MIO at the two-year follow-up compared to the control group (40.5 mm and 34.3 mm, respectively), which was statistically significant. The intervention group also reported less jaw-related problems according to the GTQ and higher functioning as measured by EORTC QLQ-C30 and QLQ-H&N35 compared to the control group. Conclusion A positive persistent effect of exercise intervention for trismus in HNC patients was found with regard to MIO, trismus-related symptoms and HRQL. Exercise intervention is important in long-term treatment of radiation-induced trismus in HNC patients. The trismus-specific questionnaire, GTQ, is a valuable tool for observing and evaluating trismus over time. PMID- 26878552 TI - Allosteric substrate switching in a voltage-sensing lipid phosphatase. AB - Allostery provides a critical control over enzyme activity, biasing the catalytic site between inactive and active states. We found that the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), which modifies phosphoinositide signaling lipids (PIPs), has not one but two sequential active states with distinct substrate specificities, whose occupancy is allosterically controlled by sequential conformations of the voltage-sensing domain (VSD). Using fast fluorescence resonance energy transfer (FRET) reporters of PIPs to monitor enzyme activity and voltage-clamp fluorometry to monitor conformational changes in the VSD, we found that Ci-VSP switches from inactive to a PIP3-preferring active state when the VSD undergoes an initial voltage-sensing motion and then into a second PIP2-preferring active state when the VSD activates fully. This two-step allosteric control over a dual-specificity enzyme enables voltage to shape PIP concentrations in time, and provides a mechanism for the complex modulation of PIP-regulated ion channels, transporters, cell motility, endocytosis and exocytosis. PMID- 26878554 TI - Effects of repetitive transcranial magnetic stimulation on lower extremity spasticity and motor function in stroke patients. AB - PURPOSE: To investigate the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on lower extremity (LE) spasticity, motor function and motor neurone excitability in chronic stroke patients. METHOD: This study was a randomised sham-controlled cross-over trial with 1-week follow-up. A total of 20 post-stroke patients were randomised to receive active (n = 10) or sham (n = 10) rTMS. Fourteen of them (7 in each group) crossed over to the sham or active rTMS after a washout period of 1 month. Interventions consist of five consecutive daily sessions of active or sham rTMS to the unaffected lower extremity motor area (1000 pulses; 1 Hz; 90% of the tibialis anterior motor threshold). Outcome measures were modified modified ashworth scale (MMAS), the H-reflex, lower extremity section of Fugl-Mayer assessment (LE-FMA) and timed UP and GO (TUG) test. All outcomes were measured at three levels in each intervention period: pre and post-intervention and 1-week follow-up. RESULTS: Friedman's test revealed significant improvement in MMAS score only after active rTMS. This improvement lasted for one week after the active rTMS. Repeated measure analysis of variance (ANOVA) showed significant time*intervention interaction for LE-FMA. There are no differences between groups for the MMAS and LE-FMA. No significant change in Hmax/Mmax ratio and TUG test was noted. CONCLUSION: Low-frequency rTMS over the LE motor area can improve clinical measures of muscle spasticity and motor function. More studies are needed to clarify the changes underlying this improvement in spasticity. Implications for Rehabilitation Spasticity is a common disorder and one of the causes of long-term disability after stroke. Physical therapy modalities, oral medications, focal intervention and surgical procedures have been used for spasticity reduction. Beneficial effect of the repetitive transcranial magnetic stimulation (rTMS) for post-stroke upper extremity spasticity reduction and motor function improvement was demonstrated in previous studies. This study shows amelioration of lower extremity spasticity and motor function improvement after five daily sessions of inhibitory rTMS to the unaffected brain hemisphere which lasted for at least 1 week following the intervention. PMID- 26878556 TI - MACRA paves way for changes in reimbursements: Physicians hopeful law will lead to more value-based care. PMID- 26878555 TI - The use of human neurons for novel drug discovery in dementia research. AB - INTRODUCTION: Although many disease models exist for neurodegenerative disease, the translation of basic research findings to clinic is very limited. Studies using freshly resected human brain tissue, commonly discarded from neurosurgical procedures, should complement on-going work using stem cell-derived human neurons and glia thus increasing the likelihood of success in clinical trials. AREAS COVERED: Herein, the authors discuss key issues in the lack of translation from basic research to clinic. They also review the evidence that human neurons, both freshly resected brain tissue and stem cell-derived neurons, such as induced pluripotent stem cells (iPSCs), can be used for analysis of physiological and molecular mechanisms in health and disease. Furthermore, the authors compare and contrast studies using live human brain tissue and studies using induced human stem cell-derived neuron models. Using an example from the area of neurodegeneration, the authors suggest that replicating elements of research findings from animals and stem cell models in resected human brain tissue would strengthen our understanding of disease mechanisms and the therapeutic strategies and aid translation. EXPERT OPINION: The use of human brain tissue alongside iPSC derived neural models can validate molecular mechanisms identified in rodent disease models and strengthen their relevance to humans. If drug target engagement and mechanism of cellular action can be validated in human brain tissue, this will increase the success rate in clinical research. The combined use of resected human brain tissue, alongside iPSC-derived neural models, could be considered a standard step in pre-clinical research and help to bridge the gap to clinical trials. PMID- 26878557 TI - Physicians say HPV testing alone can screen for cervical cancer. PMID- 26878558 TI - High vitamin D levels increase survival rates in patients with metastatic colorectal cancer. PMID- 26878559 TI - Erratum: Improving our understanding of the use of traditional complementary/alternative medicine in children with cancer. PMID- 26878560 TI - Effectiveness and safety of liraglutide after three years of treatment. AB - BACKGROUND: The aim of this study was to evaluate long-term effectiveness and safety of liraglutide in real world. METHODS: A diabetes clinic in Italy systematically collected data of all patients treated with liraglutide. Generalized hierarchical linear regression models for repeated measures were applied to assess trends over time of HbA1c, fasting plasma glucose (FPG), body weight, blood pressure and lipid profile. RESULTS: Overall, 255 patients (mean age: 63.5+/-9.7 years, men: 56.9%, mean diabetes duration: 12.0+/-8.1 years) were treated with liraglutide during 36 months. Mean HbA1c levels decreased by -1.0+/ 0.1% (P<0.0001), FPG by -46+/-6 mg/dL (P<0.0001), and body weight by -3.9+/-0.8 Kg (P<0.0001). HbA1c reduction was inversely related to diabetes duration, while body weight reduction was directly related to baseline BMI. Significant improvements in HDL-cholesterol and triglycerides levels were also documented. Trends of improvement in systolic blood pressure (SBP) levels were also found, with significant reduction in patients with baseline SBP>=140 mmHg. Treatment was well-tolerated by the vast majority of the patients. Neither severe hypoglycemia nor pancreatitis occurred. Drop-out rate was of 28.2%. Main causes of drop-out were gastrointestinal side effects and lack of efficacy. CONCLUSION: Our analysis documents a prolonged effectiveness and safety of liraglutide, even after three years of treatment. In addition to significant improvement in glycemic control and body weight, liraglutide also provides additional benefits on cardiovascular risk profile, while minimizing the risk of hypoglycemia. However, magnitude of benefits reflects specific patient characteristics that deserve further investigation. PMID- 26878561 TI - The current management of Turner Syndrome. AB - Turner Syndrome (TS) is a rare disease, with the incidence of 1 of 2500 life born females. Characteristic features are: growth retardation, gonadal dysgenesis and impairment, congenital and acquired cardiovascular disorders. New management possibilities in Turner Syndrome are coming along with the new scientific evidence on the pathogenesis of TS developmental, metabolic, cardiovascular and reproductive issues. Attitude to the growth retardation treatment and hormone replacement therapy is changing. The effectiveness of additional androgen doses for growth improvement and low estrogen doses in the early childhood for better puberty induction and metabolic outcomes has been demonstrated recently. There are some new concerns about pregnancy induced progression of cardiovascular pathology in TS. Inadequate follow-up despite strict and clear guidelines of TS patients is still an issue in the health care system in many countries. This rare disorder requires multidiscipline approach of experienced professionals. The aim of this review is to overview recent studies evaluating TS, to focus on the possibilities to avoid crucial outcomes of this disorder and to improve management and follow-up. PMID- 26878562 TI - Pre-existing diabetes in pregnancy. AB - The incidence of type 1 and type 2 diabetes amongst women of reproductive age is increasing worldwide. Despite recent advances in treatment options for diabetes outside of pregnancy, women still have a significantly increased risk of adverse obstetric outcomes including perinatal death and congenital malformation, compared to the non-diabetic population. An understanding of the physiological changes during pregnancy, management, early detection and prevention of complications and pre-pregnancy care, specific to women with pre-existing diabetes, is important in improving health outcomes in this growing group of women. This review particularly focuses on areas where there have been recent developments or controversy. PMID- 26878563 TI - Are basal and glucagon-stimulated C-peptide values predictors of response to GLP 1 receptor agonists in type 2 diabetic patients? PMID- 26878564 TI - Expression patterns of cytokeratin 5/6 and p63 in thyroid sporadic nodular goiter. PMID- 26878565 TI - Phytotherapy for diabetes mellitus: back to nature. PMID- 26878566 TI - Calculating Free Energy Changes in Continuum Solvation Models. AB - We recently showed for a large data set of pKas and reduction potentials that free energies calculated directly within the SMD continuum model compares very well with corresponding thermodynamic cycle calculations in both aqueous and organic solvents [ Phys. Chem. Chem. Phys. 2015 , 17 , 2859 ]. In this paper, we significantly expand the scope of our study to examine the suitability of this approach for calculating general solution phase kinetics and thermodynamics, in conjunction with several commonly used solvation models (SMD-M062X, SMD-HF, CPCM UAKS, and CPCM-UAHF) for a broad range of systems. This includes cluster continuum schemes for pKa calculations as well as various neutral, radical, and ionic reactions such as enolization, cycloaddition, hydrogen and chlorine atom transfer, and SN2 and E2 reactions. On the basis of this benchmarking study, we conclude that the accuracies of both approaches are generally very similar-the mean errors for Gibbs free energy changes of neutral and ionic reactions are approximately 5 and 25 kJ mol(-1), respectively. In systems where there are significant structural changes due to solvation, as is the case for certain ionic transition states and amino acids, the direct approach generally afford free energy changes that are in better agreement with experiment. PMID- 26878567 TI - Differences in medical students' academic interest and performance across career choice motivations. AB - OBJECTIVE: To investigate medical students' career choice motivation and its relationship with their academic interest and performance. METHODS: We conducted a cross-sectional study in a sample (n=207) of medical students at a private medical school in Korea, stratified by year of medical course. Data about participant demographics, career choice motivation and academic interest were collected using a self-report questionnaire. The item on career choice motivation enquired about the respondents' main reason for applying for medical school among 8 possible response options, which comprised two components of career choice motivation: intrinsic and extrinsic. The participants' levels of academic interest were measured in a Likert-type question. Participants' academic interest and Grade Point Averages (GPAs) were compared across the groups of different career motivations along with analyses of their admission scores for baseline comparisons. RESULTS: A total of 195 students completed the questionnaire (94%response rate). Seventy-four percent, (n=145; the intrinsic group) of the participants chose reasons related to intrinsic motivation, 22% (n=42; the extrinsic group) chose reasons pertaining to extrinsic motivation, and 4% (n = 8) chose other reasons for applying to medical school. The intrinsic group outperformed the extrinsic group in their GPAs, although their prior academic achievements did not differ significantly. The intrinsic group showed significantly higher levels of academic interest and also performed better in the admission interviews. CONCLUSIONS: Our study illustrates differences in medical students' academic interest and performance across career choice motivations. Further research is warranted to establish the predictive power of medical students' career choice motivation and academic interest on their academic performance. PMID- 26878568 TI - Gas-assisted electron-beam-induced nanopatterning of high-quality titanium oxide. AB - Electron-beam-induced deposition of titanium oxide nanopatterns is described. The precursor is titanium tetra-isopropoxide, delivered to the deposition point through a needle and mixed with oxygen at the same point via a flow through a separate needle. The depositions are free of residual carbon and have an EDX determined stoichiometry of TiO2.2. High resolution transmission electron microscopy and Raman spectroscopy studies reveal an amorphous structure of the fabricated titanium oxide. Ellipsometric characterization of the deposited material reveals a refractive index of 2.2-2.4 RIU in the spectral range of 500 1700 nm and a very low extinction coefficient (lower than 10(-6) in the range of 400-1700 nm), which is consistent with high quality titanium oxide. The electrical resistivity of the titanium oxide patterned with this new process is in the range of 10-40 GOmega cm and the measured breakdown field is in the range of 10-70 V MUm(-1). The fabricated nanopatterns are important for a variety of applications, including field-effect transistors, memory devices, MEMS, waveguide structures, bio- and chemical sensors. PMID- 26878570 TI - Role of Small Noncoding RNAs in Bacterial Metabolism. AB - The study of prokaryotic small RNAs is one of the most important directions in modern molecular biology. In the last decade, multiple short regulatory transcripts have been found in prokaryotes, and for some of them functional roles have been elucidated. Bacterial small RNAs are implicated in the regulation of transcription and translation, and they affect mRNA stability and gene expression via different mechanisms, including changes in mRNA conformation and interaction with proteins. Most small RNAs are expressed in response to external factors, and they help bacteria to adapt to changing environmental conditions. Bacterial infections of various origins remain a serious medical problem, despite significant progress in fighting them. Discovery of mechanisms that bacteria employ to survive in infected organisms and ways to block these mechanisms is promising for finding new treatments for bacterial infections. Regulation of pathogenesis with small RNAs is an attractive example of such mechanisms. This review considers the role of bacterial small RNAs in adaptation to stress conditions. We pay special attention to the role of small RNAs in Mycobacterium tuberculosis infection, in particular during establishment and maintenance of latent infection. PMID- 26878571 TI - Bacterial Small Regulatory RNAs and Hfq Protein. AB - Small regulatory RNA (sRNA) is a unique noncoding RNA involved in regulation of gene expression in both eukaryotic and bacterial cells. This short review discusses examples of positive and negative translation regulation by sRNAs in bacteria and participation of Hfq in these processes. The importance of structure investigation of nucleotide-protein and RNA-protein complexes for designing a model of Hfq interaction with both mRNA and sRNA simultaneously is demonstrated. PMID- 26878569 TI - Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate. AB - Available formulations of sumatriptan succinate (SS) have low bioavailability or are associated with site reactions. We developed various types of self-dissolving microneedle arrays (MNs) fabricated from sodium hyaluronate as a new delivery system for SS and evaluated their skin permeation and irritation in terms of clinical application. In vitro permeation studies with human skin, physicochemical properties (needle length, thickness and density), and penetration enhancers (glycerin, sodium dodecyl sulfate and lauric acid diethanolamide) were investigated. SS-loaded high-density MNs of 800 um in length were the optimal formulation and met clinical therapeutic requirements. Penetration enhancers did not significantly affect permeation of SS from MNs. Optical coherence tomography images demonstrated that SS-loaded high-density MNs (800 um) uniformly created drug permeation pathways for the delivery of SS into the skin. SS-loaded high-density MNs induced moderate primary skin irritations in rats, but the skin recovered within 72 h of removal of the MNs. These findings suggest that high-density MNs of 800 um in length are an effective and promising formulation for transdermal delivery of SS. To our knowledge, this is the first report of SS permeation across human skin using self-dissolving MNs. PMID- 26878572 TI - Carbonyl Stress in Bacteria: Causes and Consequences. AB - Pathways of synthesis of the alpha-reactive carbonyl compound methylglyoxal (MG) in prokaryotes are described in this review. Accumulation of MG leads to development of carbonyl stress. Some pathways of MG formation are similar for both pro- and eukaryotes, but there are reactions specific for prokaryotes, e.g. the methylglyoxal synthase reaction. This reaction and the glyoxalase system constitute an alternative pathway of glucose catabolism - the MG shunt not associated with the synthesis of ATP. In violation of the regulation of metabolism, the cell uses MG shunt as well as other glycolysis shunting pathways and futile cycles enabling stabilization of its energetic status. MG was first examined as a biologically active metabolic factor participating in the formation of phenotypic polymorphism and hyperpersistent potential of bacterial populations. The study of carbonyl stress is interesting for evolutionary biology and can be useful for constructing highly effective producer strains. PMID- 26878573 TI - Sperm-Specific Glyceraldehyde-3-Phosphate Dehydrogenase - An Evolutionary Acquisition of Mammals. AB - This review is focused on the mammalian sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDS). GAPDS plays the major role in the production of energy required for sperm cell movement and does not perform non-glycolytic functions that are characteristic of the somatic isoenzyme of glyceraldehyde-3-phosphate dehydrogenase. The GAPDS sequence is composed of 408 amino acid residues and includes an additional N-terminal region of 72 a.a. that binds the protein to the sperm tail cytoskeleton. GAPDS is present only in the sperm cells of mammals and lizards, possibly providing them with certain evolutionary advantages in reproduction. In this review, studies concerning the problems of GAPDS isolation, its catalytic properties, and its structural features are described in detail. GAPDS is much more stable compared to the somatic isoenzyme, perhaps due to the necessity of maintaining the enzyme function in the absence of protein expression. The site-directed mutagenesis approach revealed the two GAPDS specific proline residues, as well as three salt bridges, which seem to be the basis of the increased stability of this protein. As distinct from the somatic isoenzyme, GAPDS exhibits positive cooperativity in binding of the coenzyme NAD+. The key role in transduction of structural changes induced by NAD+ is played by the salt bridge D311-H124. Disruption of this salt bridge cancels GAPDS cooperativity and twofold increases its enzymatic activity instead. The expression of GAPDS was detected in some melanoma cells as well. Its role in the development of certain pathologies, such as cancer and neurodegenerative diseases, is discussed. PMID- 26878575 TI - Plant Proteases Involved in Regulated Cell Death. AB - Each plant genome encodes hundreds of proteolytic enzymes. These enzymes can be divided into five distinct classes: cysteine-, serine-, aspartic-, threonine-, and metalloproteinases. Despite the differences in their structural properties and activities, members of all of these classes in plants are involved in the processes of regulated cell death - a basic feature of eukaryotic organisms. Regulated cell death in plants is an indispensable mechanism supporting plant development, survival, stress responses, and defense against pathogens. This review summarizes recent advances in studies of plant proteolytic enzymes functioning in the initiation and execution of distinct types of regulated cell death. PMID- 26878574 TI - Role of a Structurally Equivalent Phenylalanine Residue in Catalysis and Thermal Stability of Formate Dehydrogenases from Different Sources. AB - Comparison of amino acid sequences of NAD+-dependent formate dehydrogenases (FDH, EC 1.2.1.2) from different sources and analysis of structures of holo-forms of FDH from bacterium Pseudomonas sp. 101 (PseFDH) and soya Glycine max (SoyFDH) as well as of structure of apo-form of FDH from yeast Candida boidinii (CboFDH) revealed the presence on the surface of protein globule of hydrophobic Phe residue in structurally equivalent position (SEP). The residue is placed in the coenzyme-binding domain and protects bound NAD+ from solvent. The effects of amino acid changes of the SEP on catalytic properties and thermal stability of PseFDH, SoyFDH, and CboFDH were compared. The strongest effect was observed for SoyFDH. All eight amino acid replacements resulted in increase in thermal stability, and in seven cases, increase in catalytic constant was achieved. Thermal stability of SoyFDH after mutations Phe290Asp and Phe290Glu increased 66- and 55-fold, respectively. KM values of the enzyme for substrate and coenzyme in different cases slightly increased or decreased. In case of one CboFDH, the mutein catalytic constant increased and thermal stability did not changed. In case of the second CboFDH mutant, results were the opposite. In one PseFDH mutant, amino acid change did not influence the catalytic constant, but in three others, the parameter was reduced. Two PseFDH mutants had higher and two mutants lower thermal stability in comparison with initial enzyme. Analysis of results of SEP mutagenesis in FDHs from bacterium, yeast, and plant shows that protein structure plays a key role for effect of the same amino acid changes in equivalent position in protein globule of formate dehydrogenases from different sources. PMID- 26878576 TI - Spectral Dependence of Chlorophyll Biosynthesis Pathways in Plant Leaves. AB - This review covers studies on the dependence of chlorophyll photobiosynthesis reactions from protochlorophyllide on the spectral composition of actinic light. A general scheme of the reaction sequence for the photochemical stage in chlorophyll biosynthesis for etiolated plant leaves is presented. Comparative analysis of the data shows that the use of light with varied wavelengths for etiolated plant illumination reveals parallel transformation pathways of different protochlorophyllide forms into chlorophyllide, including a pathway for early photosystem II reaction center P-680 pigment formation. PMID- 26878577 TI - Regulation of Zygotic Genome and Cellular Pluripotency. AB - Events, manifesting transition from maternal to zygotic period of development are studied for more than 100 years, but underlying mechanisms are not yet clear. We provide a brief historical overview of development of concepts and explain the specific terminology used in the field. We further discuss differences and similarities between the zygotic genome activation and in vitro reprogramming process. Finally, we envision the future research directions within the field, where biochemical methods will play increasingly important role. PMID- 26878578 TI - Small Heat Shock Proteins and Distal Hereditary Neuropathies. AB - Classification of small heat shock proteins (sHsp) is presented and processes regulated by sHsp are described. Symptoms of hereditary distal neuropathy are described and the genes whose mutations are associated with development of this congenital disease are listed. The literature data and our own results concerning physicochemical properties of HspB1 mutants associated with Charcot-Marie-Tooth disease are analyzed. Mutations of HspB1, associated with hereditary motor neuron disease, can be accompanied by change of the size of HspB1 oligomers, by decreased stability under unfavorable conditions, by changes in the interaction with protein partners, and as a rule by decrease of chaperone-like activity. The largest part of these mutations is accompanied by change of oligomer stability (that can be either increased or decreased) or by change of intermonomer interaction inside an oligomer. Data on point mutation of HspB3 associated with axonal neuropathy are presented. Data concerning point mutations of Lys141 of HspB8 and those associated with hereditary neuropathy and different forms of Charcot-Marie-Tooth disease are analyzed. It is supposed that point mutations of sHsp associated with distal neuropathies lead either to loss of function (for instance, decrease of chaperone-like activity) or to gain of harmful functions (for instance, increase of interaction with certain protein partners). PMID- 26878579 TI - Investigations of Molecular Mechanisms of Actin-Myosin Interactions in Cardiac Muscle. AB - The functional characteristics of cardiac muscle depend on the composition of protein isoforms in the cardiomyocyte contractile machinery. In the ventricular myocardium of mammals, several isoforms of contractile and regulatory proteins are expressed - two isoforms of myosin (V1 and V3) and three isoforms of tropomyosin chains (alpha, beta, and kappa). Expression of protein isoforms depends on the animal species, its age and hormonal status, and this can change with pathologies of the myocardium. Mutations in these proteins can lead to cardiomyopathies. The functional significance of the protein isoform composition has been studied mainly on intact hearts or on isolated preparations of myocardium, which could not provide a clear comprehension of the role of each particular isoform. Present-day experimental techniques such as an optical trap and in vitro motility assay make it possible to investigate the phenomena of interactions of contractile and regulatory proteins on the molecular level, thus avoiding effects associated with properties of a whole muscle or muscle tissue. These methods enable free combining of the isoforms to test the molecular mechanisms of their participation in the actin-myosin interaction. Using the optical trap and the in vitro motility assay, we have studied functional characteristics of the cardiac myosin isoforms, molecular mechanisms of the calcium-dependent regulation of actin-myosin interaction, and the role of myosin and tropomyosin isoforms in the cooperativity mechanisms in myocardium. The knowledge of molecular mechanisms underlying myocardial contractility and its regulation is necessary for comprehension of cardiac muscle functioning, its disorders in pathologies, and for development of approaches for their correction. PMID- 26878580 TI - Diversity of Potassium Channel Ligands: Focus on Scorpion Toxins. AB - Potassium (K+) channels are a widespread superfamily of integral membrane proteins that mediate selective transport of K+ ions through the cell membrane. They have been found in all living organisms from bacteria to higher multicellular animals, including humans. Not surprisingly, K+ channels bind ligands of different nature, such as metal ions, low molecular mass compounds, venom-derived peptides, and antibodies. Functionally these substances can be K+ channel pore blockers or modulators. Representatives of the first group occlude the channel pore, like a cork in a bottle, while the second group of ligands alters the operation of channels without physically blocking the ion current. A rich source of K+ channel ligands is venom of different animals: snakes, sea anemones, cone snails, bees, spiders, and scorpions. More than a half of the known K+ channel ligands of polypeptide nature are scorpion toxins (KTx), all of which are pore blockers. These compounds have become an indispensable molecular tool for the study of K+ channel structure and function. A recent special interest is the possibility of toxin application as drugs to treat diseases involving K+ channels or related to their dysfunction (channelopathies). PMID- 26878581 TI - Beta-Amyloid and Tau-Protein: Structure, Interaction, and Prion-Like Properties. AB - During the last twenty years, molecular genetic investigations of Alzheimer's disease (AD) have significantly broadened our knowledge of basic mechanisms of this disorder. However, still no unambiguous concept on the molecular bases of AD pathogenesis has been elaborated, which significantly impedes the development of AD therapy. In this review, we analyze issues concerning processes of generation of two proteins (beta-amyloid peptide and Tau-protein) in the cell, which are believed to play the key role in AD genesis. Until recently, these agents were considered independently of each other, but in light of the latest studies, it becomes clear that it is necessary to study their interaction and combined effects. Studies of mechanisms of toxic action of these endogenous compounds, beginning from their interaction with known receptors of main neurotransmitters to specific peculiarities of functioning of signal intracellular pathways upon development of this pathology, open the way to development of new pharmaceutical substances directed concurrently on key mechanisms of interaction of toxic proteins inside the cell and on the pathways of their propagation in the extracellular space. PMID- 26878582 TI - Detection of Intermolecular Interactions Based on Surface Plasmon Resonance Registration. AB - Methods for registration of intermolecular interactions based on the phenomenon of surface plasmon resonance (SPR) have become one of the most efficient tools to solve fundamental and applied problems of analytical biochemistry. Nevertheless, capabilities of these methods are often insufficient to detect low concentrations of analytes or to screen large numbers of objects. That is why considerable efforts are directed at enhancing the sensitivity and efficiency of SPR-based measurements. This review describes the basic principles of the detection of intermolecular interactions using this method, provides a comparison of various types of SPR detectors, and classifies modern approaches to enhance sensitivity and efficiency of measurements. PMID- 26878583 TI - Broadband acoustic properties of a murine skull. AB - It has been well recognized that the presence of a skull imposes harsh restrictions on the use of ultrasound and optoacoustic techniques in the study, treatment and modulation of the brain function. We propose a rigorous modeling and experimental methodology for estimating the insertion loss and the elastic constants of the skull over a wide range of frequencies and incidence angles. A point-source-like excitation of ultrawideband acoustic radiation was induced via the absorption of nanosecond duration laser pulses by a 20 MUm diameter microsphere. The acoustic waves transmitted through the skull are recorded by a broadband, spherically focused ultrasound transducer. A coregistered pulse-echo ultrasound scan is subsequently performed to provide accurate skull geometry to be fed into an acoustic transmission model represented in an angular spectrum domain. The modeling predictions were validated by measurements taken from a glass cover-slip and ex vivo adult mouse skulls. The flexible semi-analytical formulation of the model allows for seamless extension to other transducer geometries and diverse experimental scenarios involving broadband acoustic transmission through locally flat solid structures. It is anticipated that accurate quantification and modeling of the skull transmission effects would ultimately allow for skull aberration correction in a broad variety of applications employing transcranial detection or transmission of high frequency ultrasound. PMID- 26878584 TI - Characterization of Antibodies for Grain-Specific Gluten Detection. AB - Gluten ingestion causes immunoglobulin E (IgE)-mediated allergy or celiac disease in sensitive individuals, and a strict gluten-free diet greatly limits food choices. Immunoassays such as enzyme-linked immunosorbent assay (ELISA) are used to quantify gluten to ensure labeling compliance of gluten-free foods. Anti gluten antibodies may not exhibit equal affinity to gluten from wheat, rye, and barley. Moreover, because wheat gluten is commonly used as a calibrator in ELISA, accurate gluten quantitation from rye and barley contaminated foods may be compromised. Immunoassays utilizing grain-specific antibodies and calibrators may help improve gluten quantitation. In this study, polyclonal antibodies raised against gluten-containing grain-specific peptides were characterized for their immunoreactivity to gluten from different grain sources. Strong immunoreactivity to multiple gluten polypeptides from wheat, rye, and barley was observed in the range 34 to 43 kDa with anti-gliadin, 11 to 15 and 72 to 95 kDa with anti secalin, and 30 to 43 kDa with anti-hordein peptide antibodies, respectively. Minimal or no cross-reactivity with gluten from other grains was observed among these antibodies. The anti-consensus peptide antibody raised against a repetitive amino acid sequence of proline and glutamine exhibited immunoreactivity to gluten from wheat, rye, barley, and oat. The antibodies exhibited similar immunoreactivity with most of the corresponding grain cultivars by ELISA. The high specificity and minimal cross-reactivity of grain-specific antibodies suggest their potential use in immunoassays for accurate gluten quantitation. PMID- 26878585 TI - HIGH AND LOW THRESHOLD FOR STARTLE REACTIVITY ASSOCIATED WITH PTSD SYMPTOMS BUT NOT PTSD RISK: EVIDENCE FROM A PROSPECTIVE STUDY OF ACTIVE DUTY MARINES. AB - BACKGROUND: Heightened startle response is a symptom of PTSD, but evidence for exaggerated startle in PTSD is inconsistent. This prospective study aimed to clarify whether altered startle reactivity represents a trait risk-factor for developing PTSD or a marker of current PTSD symptoms. METHODS: Marines and Navy Corpsmen were assessed before (n = 2,571) and after (n = 1,632) deployments to Iraq or Afghanistan with the Clinician-Administered PTSD Scale (CAPS). A predeployment startle-threshold task was completed with startle probes presented over 80-114 dB[A] levels. Latent class mixture modeling identified three growth classes of startle performance: "high," "low," and "moderate" threshold classes. Zero-inflated negative binomial regression was used to assess relationships between predeployment startle threshold and pre- and postdeployment psychiatric symptoms. RESULTS: At predeployment, the low-threshold class had higher PTSD symptom scores. Relative to the moderate-threshold class, low-threshold class membership was associated with decreased likelihood of being symptom-free at predeployment, based on CAPS, with particular associations with numbing and hyperarousal subscales, whereas high-threshold class membership was associated with more severe predeployment PTSD symptoms, in particular avoidance. Associations between low-threshold membership and CAPS symptoms were independent from measures of trauma burden, whereas associations between high-threshold membership and CAPS were not. Predeployment startle threshold did not predict postdeployment symptoms. CONCLUSIONS: This study found that both low startle threshold (heightened reactivity) and high startle threshold (blunted reactivity) were associated with greater current PTSD symptomatology, suggesting that startle reactivity is associated with current PTSD rather than a risk marker for developing PTSD. PMID- 26878586 TI - Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity. AB - Natural armadillo repeat proteins (nArmRP) like importin-alpha or beta-catenin bind their target peptides such that each repeat interacts with a dipeptide unit within the stretched target peptide. However, this modularity is imperfect and also restricted to short peptide stretches of usually four to six consecutive amino acids. Here we report the development and characterization of a regularized and truly modular peptide-specific binding protein, based on designed armadillo repeat proteins (dArmRP), binding to peptides of alternating lysine and arginine residues (KR)n. dArmRP were obtained from nArmRP through cycles of extensive protein engineering, which rendered them more uniform. This regularity is reflected in the consistent binding of dArmRP to (KR)-peptides, where affinities depend on the lengths of target peptides and the number of internal repeats in a very systematic manner, thus confirming the modularity of the interaction. This exponential dependency between affinity and recognition length suggests that each module adds a constant increment of binding energy to sequence-specific recognition. This relationship was confirmed by comprehensive mutagenesis studies that also reveal the importance of individual peptide side chains. The 1.83 A resolution crystal structure of a dArmRP with five identical internal repeats in complex with the cognate (KR)5 peptide proves a modular binding mode, where each dipeptide is recognized by one internal repeat. The confirmation of this true modularity over longer peptide stretches lays the ground for the design of binders with different specificities and tailored affinities by the assembly of dipeptide-specific modules based on armadillo repeats. PMID- 26878588 TI - [Identification of the party responsible for restoring the water quality according to the German Potable Water Act in buildings belonging to a semiautonomous condominium community]. AB - When drinking water contaminations occur in installations belonging to a semiautonomous condominium community (Wohnungseigentumsgemeinschaft) and the water installation's final paths being owned by the various condominium owners, the German legal definition of the party responsible has a broad reach. Therefore, authorities should address the condominium community, the condominium owners and the community administrator (WEG-Verwalter). PMID- 26878587 TI - Somatosensory brainstem, thalamus, and cortex of the California sea lion (Zalophus californianus). AB - Pinnipeds (sea lions, seals, and walruses) are notable for many reasons, including their ape-sized brains, their adaptation to a coastal niche that combines mastery of the sea with strong ties to land, and the remarkable abilities of their trigeminal whisker system. However, little is known about the central nervous system of pinnipeds. Here we report on the somatosensory areas of the nervous system of the California sea lion (Zalophus californianus). Using stains for Nissl, cytochrome oxidase, and vesicular glutamate transporters, we investigated the primary somatosensory areas in the brainstem, thalamus, and cortex in one sea lion pup and the external anatomy of the brain in a second pup. We find that the sea lion's impressive array of whiskers is matched by a large trigeminal representation in the brainstem with well-defined parcellation that resembles the barrelettes found in rodents but scaled upward in size. The dorsal column nuclei are large and distinct. The ventral posterior nucleus of the thalamus has divisions, with a large area for the presumptive head representation. Primary somatosensory cortex is located in the neocortex just anterior to the main vertical fissure, and precisely locating it as we do here is useful for comparing the highly gyrified pinniped cortex with that of other carnivores. To our knowledge this work is the first comprehensive report on the central nervous system areas for any sensory system in a pinniped. The results may be useful both in the veterinary setting and for comparative studies related to brain evolution. PMID- 26878589 TI - [Cooperation in Public Health: Formative Evaluation of the Model Project "Regional Health Conferences" in Bavaria]. AB - Aim of the study: Health conferences offer opportunities for better cooperation and coordination in local health management. The aim of the explorative evaluation study was to assess structures, processes and results of "Regional Health Conferences (RGK)" in 3 model regions, to inform about potential for development and to test their transferability to other regions. Method: After the model project had been up and running for 18 months (08/2013 to 12/2014), a survey of 80 participants of the RGK in 3 regions was conducted, based on a semi standardized questionnaire. The response rate was 90%. The results were complemented by document analysis and an additional survey of the managers of the RGK. Results: The 3 RGK were established with their agencies and 13 working groups on health care. Almost all participants felt that the number of members was appropriate and that the main stakeholders were represented. According to a large part of the respondents, the majority actively took part in the RGK and usually everyone had the equal opportunity to propose a topic. Although almost half of the respondents reported conflicts, the atmosphere was constructive for 3 quarters of them. Nearly all the interviewees confirmed the importance of a chairman and a manager of the agency, as well as the positive influence of the moderator. Almost everyone agreed that RGK are suited to improve health care and cooperation. From the participants' point of view, the main problems were identified; 94% of the respondents agreed that the previous work could be regarded as successful and 91% were satisfied or rather satisfied with the processes of the RGK. The level of satisfaction was similar among the three model regions, but it varied among the member groups; 98% of the interviewees would also take part in the future. Conclusion: According to this survey, RGK are an appropriate platform for coordination, exchange und cooperation of stakeholders and a good instrument for cooperation. In Bavaria, the approach will be further improved as well as extended to other regions based on a new concept called "Health Regionsplus". PMID- 26878590 TI - ["What you will": Results of an Empirical Analysis of the Need to Improve Work life Balance for Physicians]. AB - STUDY AIMS: This study assessed the perceived need for clinics to improve work life balance of physicians. Hospitals are increasingly facing demands to offer physicians working conditions that allow greater balance between family life and pursuit of career. Simultaneously, hospitals could consider this an opportunity to stand out as attractive employers. METHODS: N=120 doctors of the medical faculty and N=679 medical students in their premedical and clinical training participated online. RESULTS: The results of the Work-Family/Family-Work Conflict Scale (WFC/FWC) showed physicians to have a decreased work/life balance when starting to work professionally, especially with a child. Ninety percent of the respondents considered the following arrangements to be especially helpful: temporary work interruptions in an emergency, part-time positions or emergency childcare. The doctors also expressed their wish to be actively supported by their supervisors on the topic of work/life balance. CONCLUSION: This analysis on work-family balance shows the need for change in the studied samples. Based on the measures that were determined to be helpful, hospitals can make conclusions about what concrete steps of action can be taken. Additionally, WFC/FWC could be used as a standardized analysis measure to assess the load imposed on physicians by family on work place and vice versa. PMID- 26878591 TI - [The Psychometric Properties of the Abdominal Surgery Impact Scale]. AB - Background: Assessment of quality of life immediately after abdominal surgery is critical; however, potent tools that provide timely information about patient health are required in order to assess and improve postoperative quality of care. Interestingly, such assessment scales for early postoperative quality of life do not exist in German. The aim of this pilot study was to translate the English version of the "Abdominal Surgery Impact Scale" (ASIS) into German and to empirically test the German version. Methods: After the standardized translation, 30 German-speaking patients who had undergone visceral surgery (laparotomy) were recruited at the ward of the Bern University Hospital Visceral Surgery and Medicine. The internal consistency of the translated instrument (ASIS-D) was assessed on the third postoperative day; reliability, retest-reliability and construct validity were also assessed on the fifth postoperative day. Results: ASIS-D faithfully represented the content of the original version. Cronbach's alpha overall was 0.85 and for the 6 subscales 0.45-0.88. The overall score of retest-reliability was 0.57** and the construct validity was confirmed. Conclusion: The ASIS-D was shown to be reliable and valid even if other investigations are necessary. It provides specific insights into special postoperative symptoms such as wound pain and postoperative quality of sleep. After further tests, it might be suitable not only for capturing the short-term postal-surgical quality of life, but possibly also for evaluating nursing interventions. PMID- 26878592 TI - The Spectrum of Recovery From Fracture-Induced Vertebral Deformity in Pediatric Leukemia. AB - Vertebral fractures (VF) are a frequent complication of acute lymphoblastic leukemia. Some children with VF undergo vertebral body reshaping to the point of complete restoration of normal vertebral dimensions. Others are left with permanent vertebral deformity if the degree of reshaping has been incomplete by the time of final adult height attainment. In this report, we describe three children with painful VF at leukemia diagnosis or during chemotherapy. Each patient highlights different clinical trajectories in their recovery from VF and underscores the need for osteoporosis intervention trials with the goal to prevent permanent vertebral deformity in selected patients. PMID- 26878593 TI - C-ON Bond Homolysis of Alkoxyamines, Part 11: Activation of the Nitroxyl Fragment. AB - A few years ago, Bagryanskaya and colleagues (J. Org. Chem. 2011) showed that protonation of the nitroxyl fragment deactivated the alkoxyamine C-ON bond. Conversely, our group showed that protonation (Chem. Commun. 2011), as well as other chemical reactions such as oxidation or amine quaternization (Org. Lett. 2012), of the pyridyl moiety carried by the alkyl fragment was suitable to activate the homolysis of the C-ON bond. To pursue our goal of applying alkoxyamines as theranostic agents (Org. Biomol. Chem. 2014 and Mol. Pharmaceutics 2014) by activation of the C-ON bond homolysis, we turned our interest to the chemical activation of the nitroxyl fragment by oxidation/reduction of selected functions. Conversion of a hydroxyl group located close to the nitroxyl moiety successively into aldehyde, then acid, and eventually into ester, led to a successive decrease in kd. PMID- 26878594 TI - Integration of traditional systems and advanced oxidation process technologies for the industrial treatment of olive mill wastewaters. AB - A complete industrial treatment system (involving the integration of coagulation/flocculation and Fenton processes) to depurate real wastewaters coming from two-phase olive oil production mills has been studied. The experimental results indicated that at the end of this combined strategy, involving a primary physical separation stage followed by Fenton's chemical oxidation, chemical oxygen demand (COD) is reduced up to 90% and total polyphenols' concentration is decreased up to 92%. The treated stream biodegradability (BOD5/COD) reached 0.52 and the Total Suspended Solids (TSSs) and Total Dissolved Solids (TDSs) decreased up to 95% and 69%, respectively. Fenton's procedure was optimized bearing in mind the pH adjustment step, different procedures for hydrogen peroxide addition and the use of coagulants instead of the chemical precipitation (by raising pH) to promote iron sludge settling. Our results demonstrated that pH (3.0 +/- 0.1) control during the oxidation reaction improves the oxidation efficiency. Moreover, the final NaOH addition is essential to a better sludge formation and consequent precipitation of the residual iron removing also some organic matter. PMID- 26878595 TI - Chemically Conjugated Carbon Nanotubes and Graphene for Carrier Modulation. AB - Nanocarbons such as fullerene and carbon nanotubes (CNT) in late 20th century have blossomed nanoscience and nanotechnology in 21st century, which have been further proliferated by the new finding of graphene and have indeed opened a new carbon era. Several new branches of research, for example, zero-dimensional nanoparticles, one-dimensional nanowires, and two-dimensional insulating hexagonal boron nitride, and semiconducting and metallic transition metal dichalcogenides including the recently emerging black phosphorus, have been explored and numerous unprecedented quantum mechanical features have been revealed, that have been hardly accessible otherwise. Extensive research has been done on devices and applications related to such materials. Many experimental instruments have been developed with high sensitivity and improved spatial and temporal resolution to detect such tiny objects. The need for multidisciplinary research has been growing stronger than ever, which will be the tradition in the next few decades. In this Account, we will demonstrate an example of multidisciplinary effort of utilizing CNTs and graphene for electronics by modulating electronic structures. While there are several methods of modifying electronic structures of nanocarbons such as gate bias, contact metal, and conventional substitutional doping, we focus on chemical doping approaches here. We first introduce the concept of chemical doping on CNTs and graphene in terms of electronegativity of molecules and electrochemical potential of CNTs and graphene. To understand the relationship of electrochemical potential of CNTs and graphene to electronegativity of molecules, we propose a simple water bucket model: how to fill or drain water (electrons in CNTs or graphene) in the bucket (density of states) by the chemical dopants. The doping concept is then demonstrated experimentally by tracking the absorption spectroscopy, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, Raman spectroscopy, transmittance, and transport measurements and by relating them to the reduction potential of molecules relative to that of CNTs or graphene. Two effects of chemical doping in electronics, transparent conducting films, and field effect transistors are extensively discussed. One critical issue, the stability of chemical dopants under ambient conditions, is further discussed. We believe that the presented doping concept will be useful tools for other low dimensional materials such as recently emerging transition metal dichalcogenides and black phosphorus. PMID- 26878596 TI - A Real-World Perspective on Molecular Design. AB - We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction. PMID- 26878597 TI - Factors Associated with Suicidality Among a National Sample of Transgender Veterans. AB - Correlates of past-year suicidal ideation and lifetime suicide risk among a national sample of transgender veterans were examined. An online, convenience sample of 212 U.S. transgender veterans participated in a cross-sectional survey in February-May 2014. We evaluated associations between sociodemographic characteristics, stigma, mental health, and psychosocial resources with past-year suicidal ideation and lifetime suicide plans and attempts. Participants reported high rates of past-year suicidal ideation (57%) as well as history of suicide plan or attempt (66%). Transgender-related felt stigma during military service and current posttraumatic stress disorder and depressive symptoms were associated with suicide outcomes as were economic and demographic factors. PMID- 26878598 TI - Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. AB - Ovarian cancer is a leading cause of cancer-related death in women and the most lethal gynecological malignancy in the developed world. The morbidity and mortality of ovarian cancer underscore the need for novel treatment options. Artesunate (ART) is a well-tolerated anti-malarial drug that also has anti-cancer activity. In this study, we show that ART inhibited the in vitro growth of a panel of ovarian cancer cell lines, as well as the growth of ovarian cancer cells isolated from patients. Moreover, ART decreased tumor growth in vivo in a mouse model of ovarian cancer. ART-treated ovarian cancer cells showed a strong induction of reactive oxygen species (ROS) and reduced proliferation. ROS dependent cell cycle arrest occurred in the G2/M phase whereas ROS-independent cell cycle arrest occurred in the G1 phase, depending on the concentration of ART to which ovarian cancer cells were exposed. The anti-proliferative effect of ART was associated with altered expression of several key cell cycle regulatory proteins, including cyclin D3, E2F-1, and p21, as well as inhibition of mechanistic target of rapamycin signaling. Exposure of ovarian cancer cells to higher concentrations of ART resulted in ROS-dependent DNA damage and cell death. Pretreatment of ovarian cancer cells with a pan-caspase inhibitor or ferroptosis inhibitor decreased but did not completely eliminate ART-mediated cytotoxicity, suggesting the involvement of both caspase-dependent and caspase-independent pathways of killing. These data show that ART has potent anti-proliferative and cytotoxic effects on ovarian cancer cells, and may therefore be useful in the treatment of ovarian cancer. (c) 2016 Wiley Periodicals, Inc. PMID- 26878599 TI - Qualitative Comparison of Women's Perspectives on the Functions and Benefits of Group and Individual Prenatal Care. AB - INTRODUCTION: Women's definitions and experiences of the functions and benefits of their routine prenatal care are largely absent from research and public discourse on prenatal care outcomes. This qualitative study aimed to develop a framework of women's prenatal care experiences by comparing the experiences of women in individual and group prenatal care. METHODS: We conducted serial qualitative interviews with racially diverse low-income women receiving individual prenatal care (n = 14) or group prenatal care (n = 15) through pregnancy and the early postpartum period. We completed 42 second-trimester, 48 third-trimester, and 44 postpartum interviews. Using grounded theory, the semistructured interviews were coded for themes, and the themes were integrated into an explanatory framework of prenatal care functions and benefits. RESULTS: Individual and group participants described similar benefits in 3 prenatal care functions: confirming health, preventing and monitoring medical complications, and building supportive provider relationships. For the fourth function, educating and preparing, group care participants experienced more benefits and different benefits. The benefits for group participants were enhanced by the supportive group environment. Group participants described greater positive influences on stress, confidence, knowledge, motivation, informed decision making, and health care engagement. DISCUSSION: Whereas pregnant women want to maximize their probability of having a healthy newborn, other prenatal care outcomes are also important: reducing pregnancy-related stress; developing confidence and knowledge for improving health; preparing for labor, birth, and newborn care; and having supportive relationships. Group prenatal care may be more effective in attaining these outcomes. Achieving these outcomes is increasingly relevant in health care systems prioritizing woman-centered care and improved birth outcomes. How to achieve them should be part of policy development and research. PMID- 26878600 TI - Regioselective Ir(III)-catalyzed C-H alkynylation directed by 7-azaindoles. AB - Herein we report a novel iridium(iii)-catalyzed ortho-mono-alkynylation of 7 azaindoles under mild conditions. This approach provides a general and straightforward access to form novel 7-azaindole derivatives with ample substrate scope and broad group tolerance. PMID- 26878601 TI - 4-Component relativistic calculations of L3 ionization and excitations for the isoelectronic species UO2(2+), OUN(+) and UN2. AB - We present a 4-component relativistic study of uranium 2p3/2 ionization and excitation in the isoelectronic series UO2(2+), OUN(+) and UN2. We calculate ionization energies by DeltaSCF at the Hartree-Fock (HF) and Kohn-Sham (KS) level of theory. At the DeltaHF level we observe a perfectly linear chemical shift of ionization energies with respect to uranium atomic charges obtained from projection analysis. We have also developed a non-canonical 2nd-order Moller Plesset code for wave function based correlation studies. We observe the well known failure of Koopmans' theorem for core ionization due to the dominance of orbital relaxation over electron correlation effects. More unexpectedly, we find that the correlation contribution has the same sign as the relaxation contribution and show that this is due to a strong coupling of relaxation and correlation. We simulate uranium L3 XANES spectra, dominated by 2p3/2 -> U6d transitions, by restricted excitation window time-dependent density functional theory (REW-TDDFT) and the complex polarization propagator (CPP) approach and demonstrate that they give identical spectra when the same Lorentz broadening is chosen. We also simulate XANES spectra by the Hartree-Fock based static exchange (STEX) method and show how STEX excitation energies can be reproduced by time dependent Hartree-Fock calculations within the Tamm-Dancoff approximation. We furthermore show that Koopmans' theorem provide a correct approximation of ionization energies in the linear response regime and use this observation to align REW-TDDFT and CPP spectra with STEX ones. We point out that the STEX method affords the most detailed assignment of spectra since it employs virtual orbitals optimized for the selected core ionization. The calculated XANES spectra reflect the loss of bound virtual orbitals as the molecular charge is reduced along the isoelectronic series. PMID- 26878602 TI - Sublethal effect of agronomical surfactants on the spider Pardosa agrestis. AB - In addition to their active ingredients, pesticides contain also additives - surfactants. Use of surfactants has been increasing over the past decade, but their effects on non-target organisms, especially natural enemies of pests, have been studied only very rarely. The effect of three common agrochemical surfactants on the foraging behavior of the wolf spider Pardosa agrestis was studied in the laboratory. Differences in short-term, long-term, and overall cumulative predatory activities were investigated. We found that surfactant treatment significantly affected short-term predatory activity but had no effect on long-term predatory activity. The surfactants also significantly influenced the cumulative number of killed prey. We also found the sex-specific increase in cumulative kills after surfactants treatment. This is the first study showing that pesticide additives have a sublethal effect that can weaken the predatory activity of a potential biological control agent. More studies on the effects of surfactants are needed to understand how they affect beneficial organisms in agroecosystems. PMID- 26878603 TI - Adsorption and desorption of dissolved organic matter by carbon nanotubes: Effects of solution chemistry. AB - Increasing use of carbon nanotubes (CNTs) has led to their introduction into the environment where they can interact with dissolved organic matter (DOM). This study focuses on solution chemistry effects on DOM adsorption/desorption processes by single-walled CNTs (SWCNTs). Our data show that DOM adsorption is controlled by the attachment of DOM molecules to the SWCNTs, and that the initial adsorption rate is dependent on solution parameters. Adsorbed amount of DOM at high ionic strength was limited, possibly due to alterations in SWCNT bundling. Desorption of DOM performed at low pH resulted in additional DOM adsorption, whereas at high pH, adsorbed DOM amount decreased. The extent of desorption conducted at increased ionic strength was dependent on pre-adsorbed DOM concentration: low DOM loading stimulated additional adsorption of DOM, whereas high DOM loading facilitated release of adsorbed DOM. Elevated ionic strength and increased adsorbed amount of DOM reduced the oxidation temperature of the SWCNTs, suggesting that changes in the assembly of the SWCNTs had occurred. Moreover, DOM coated SWCNTs at increased ionic strength provided fewer sites for atrazine adsorption. This study enhances our understanding of DOM-SWCNT interactions in aqueous systems influenced by rapid changes in salinity, and facilitates potential use of SWCNTs in water-purification technologies. PMID- 26878604 TI - Predictability of physicochemical properties of polychlorinated dibenzo-p-dioxins (PCDDs) based on single-molecular descriptor models. AB - Polychlorinated dibenzo-p-dioxins (PCDDs) are of global concern due to their persistence, bioaccumulation and toxicity. Although the fate of PCDDs in the environment is determined by their physical-chemical properties, such as aqueous solubility, vapor pressure, octanol/water-, air/water-, and octanol/water partition coefficients, experimental property data on the entire set of 75 PCDD congeners are limited. The quantitative structure-property relationship (QSPR) approach is applied to predict the properties of all PCDD congeners. Experimental property data available from the literature are correlated against 16 molecular descriptors of five types. Reported and newly developed QSPR models for PCDDs are presented and reviewed. The values calculated by the best QSPRs are further adjusted to satisfy fundamental thermodynamic relationships. Although the single descriptor models with chlorine number, molar volume, solvent accessible surface area and polarizability are based on good statistical results, these models cannot distinguish among PCDDs having the same chlorine number. The QSPR model based on the hyper-Wiener index of quantum-chemical descriptor gives useful statistical results and is able to distinguish among congeners with the same chlorine number, as well as satisfying thermodynamic relationships. The resulting consistent properties of the 75 PCDD congeners can be used for environmental modeling. PMID- 26878605 TI - Luminescent Triphosphine Cyanide d(10) Metal Complexes. AB - Coinage metal cyanides efficiently react with a triphosphine. PPh2C6H4-PPh C6H4PPh2 (P(3)). to give the complexes M(P(3))CN, where M = Cu (1), Ag (2), and Au (3), which can further interact with coordinatively unsaturated metal centers [M(P(3))](+) to give the homobimetallic [(P(3))M-CN-M(P(3))](+)X(-) [M = Cu (4a with X(-) = CF3SO3(-) and 4b with X(-) = BF4(-)), Ag (5)] or heterometallic [(P(3))Au-CN-Ag(P(3))](+) (6) species. Extension of this approach also provided the trinuclear complex [(P(3))Cu-NC-Au-CN-Cu(P(3))](+) (7). Compounds 1-5 were characterized in the solid state by X-ray crystallography. The NMR spectroscopic studies revealed that all of the complexes except 6 retain their structures in solution. The title compounds are luminescent in the solid state, with quantum yields ranging from 8 to 87%. The observed photoemission originates mainly from the metal-to-ligand charge-transfer states according to time-dependent density functional theory computational studies. The crystalline bimetallic Cu complexes 4a/4b demonstrate extremely high sensitivity of the emission intensity to molecular O2 (KSV1 = 639 atm(-1) and LOD = 0.010% for 3 times the signal-to-noise ratio). PMID- 26878606 TI - The prevalence of alcohol and psychotropic drugs in fatalities of road-traffic accidents in Jordan during 2008-2014. AB - OBJECTIVE: Several studies confirmed alcohol and psychotropic drug consumption as important risk factors underlying fatal accidents. This paper presents updated toxicological findings in the fatalities of road traffic accidents of Amman district, in order to have an overall picture of the occurrence of these substances in these victims in Jordan. METHOD: Over a seven-year period (2008 2014), 2743, autopsies were conducted at Jordan University Hospital in which the sum of n = 311 (11.38%) were victims of road traffic accidents. Blood samples from these victims were collected. Toxicology screening for psychotropic drugs and alcohol was conducted on these samples, and the results were analyzed according to age, sex and victim's status. RESULTS: This study revealed that Alcohol and psychotropic drugs were positive in 36.5%, (n = 58) of the cases, and for alcohol alone (n = 13, 37.1%). The majority of the victims were pedestrians (n = 155, 49.8%). Additionally, 29.6% (n = 92) of the cases were of ages 19-29. Detected psychotropic drugs were benzodiazepines, barbiturates. None of the collected specimens were positive for illicit cocaine, amphetamines or cannabis. CONCLUSIONS: The results from this study proved the existence of alcohol and psychotropic drugs in the victims of road traffic accidents; Indicating an association between the uses of these substances in accident involvement. Though having some limitations, other conclusions require further data collection, cooperation with related parties in Jordan, and utilizing simple extended toxicological screens. PMID- 26878607 TI - Response to Edwards GA. Mimics of child abuse: Can choking explain abusive head trauma? PMID- 26878609 TI - Freezing, thawing and aging effects on beef tenderness from Bos indicus and Bos taurus cattle. AB - The objective of this study was to determine the effects of freezing prior to aging on the meat tenderness of young Nellore and Aberdeen Angus bulls. Samples of the longissimus thoracis muscle were submitted to two treatments: conventional aging and freezing (-20 degrees C for 40 days) followed by thawing and aging periods. The meats were evaluated after 0, 7, 14 and 21 aging days (1 degrees C). Freezing increased (P<0.05) purge, cooking loss and total exudate loss throughout aging. Nellore meats had greater total exudate loss and shorter sarcomere lengths (P<0.05). Freezing increased proteolysis during aging in the meats of both breeds, but reduced shear force was found (P<0.05) only in Aberdeen Angus meats and only at time zero. These results suggest that the meat tenderizing process by freezing prior to aging may contribute to meat tenderness in the first weeks of aging, but it is dependent on the animal breed. PMID- 26878610 TI - Effect of pomegranate peel extract on lipid and protein oxidation in beef meatballs during refrigerated storage. AB - Antioxidant effect of pomegranate peel extract (PE) to retard lipid and protein oxidation was investigated in meatballs during refrigerated storage at 4+/-1 degrees C. Concentrated lyophilised water extract of pomegranate peel was incorporated into freshly minced beef meat at 0.5% and 1% concentrations and compared with 0.01% butylated hydroxytoluene (BHT) as a reference and control (without any antioxidant). PE showed high phenolic content and antioxidant activity. In PE added samples, thiobarbituric acid reactive substances (TBARS) value, peroxide formation, loss of sulfhydryl groups and formation of protein carbonyls were lower than control (P<0.01) after 8 days of storage. Sensory evaluation with respect to colour and rancid odour revealed that PE incorporation in meatballs prolonged the refrigerated storage up to 8 days. Addition of both 0.5 and 1% PE in meatballs reduced lipid and protein oxidation and improved sensory scores. These results indicated that PE was effective on retarding lipid and protein oxidation. PMID- 26878611 TI - Molecular simulations of imidazolium-based tricyanomethanide ionic liquids using an optimized classical force field. AB - Imidazolium-based ionic liquids (ILs) incorporating the tricyanomethanide ([TCM( )]) anion are studied using an optimized classical force field. These ILs are very promising candidates for use in a wide range of cutting-edge technologies and, to our knowledge, it is the first time that this IL family is subject to a molecular simulation study with the use of a classical atomistic force field. The [C4mim(+)][TCM(-)] ionic liquid at 298.15 K and at atmospheric pressure was used as the basis for force field optimization which primarily involved the determination of the Lennard-Jones parameters of [TCM(-)] and the implementation of three quantum mechanical schemes for the calculation of the partial charge distribution and the identification of the appropriate scaling factor for the reduction of the total ionic charge. The optimized force field was validated by performing simulations of the 1-alkyl-3-methylimidazolium tricyanomethanide ([Cnmim(+)][TCM(-)], n = 2, 4, 6, and 8) IL family at various temperatures. The results for density, self-diffusivity and viscosity are in very good agreement with the available experimental data for all ILs verifying that the force field reliably reproduces the behaviour of the imidazolium-based [TCM(-)] IL family in a wide temperature range. Furthermore, a detailed analysis of the microscopic structure and the complex dynamic behaviour of the ILs under study was performed. PMID- 26878612 TI - Senna leaf extracts induced Ca(+2) homeostasis in a zoonotic tapeworm Hymenolepis diminuta. AB - Context Plants and plant products have been used in traditional medicine as anthelmintic agents in human and veterinary medicine. Three species of Senna plant, S. alata (L), S. alexandrina (M) and S. occidentalis (L.) Link (Fabaceae) have been shown to have a vermicidal/vermifugal effect on a zoonotic tapeworm Hymenolepis diminuta (Rudolphi) (Cyclophyllidean). Objective The present study validates the mode of action of these Senna plants on the parasite. The alcoholic leaf extract was determined to obtain information on the intracellular free calcium concentration level. Materials and methods Hymenolepis diminuta was maintained in Sprague-Dawley rat model for 2 months. Live parasites collected from infected rat intestine were exposed to 40 mg/mL concentration of each plant extracts prepared in phosphate buffer saline at 37 degrees C, till parasite gets paralyzed. The rate of efflux of calcium from the parasite tissue to the medium and the level of intracellular Ca(2+ )concentration were determined by an atomic absorption spectroscopy. Results This study revealed that exposure of the worms to the plant extract leads to disruption in intracellular calcium homeostasis. A significant increase (44.6% and 25%) of efflux in Ca(2+ )from the tissue to the incubated medium was observed. Senna alata showed high rate of efflux (5.32 mg/g) followed by S. alexandria and S. occidentalis (both 4.6 mg/g) compared with control (3.68 mg/g). Discussion and conclusion These results suggest that leaf extracts caused membrane permeability to Ca(2+ )after vacuolization of the tegument under stress and the extracts may contain compound that can be used as a chemotherapeutic agent. PMID- 26878614 TI - [A wrong move in an amateur football player reveals a light chain myeloma]. AB - Light chain multiple myeloma is a hematologic malignancy characterized by an excess of tumor plasma cells in the bone marrow and a monoclonal light chain in blood. It is generally diagnosed in patients aged 60-75 years old. Hypercalcemia, anemia, kidney failure, and bone pains are the main clinical and biological signs. Here is an atypical case report about a 30 year-old man who was diagnosed a light chain multiple myeloma. This patient had been suffering from back pain for 5 months. Osteolytic lesions were discovered on X-rays prescribed by the family practitioner. Admitted to the Emergency department, all blood tests showed results within the normal range. The serum protein electrophoresis was also normal. Only the urine analysis showed proteinuria. The urine immunofixation electrophoresis showed a massive kappa light chain. The bone marrow aspiration cell count confirmed the myeloma diagnosis with an infiltration of dystrophic plasma cells. The patient was transferred to the hematology ward of Necker Hospital for treatment of light chain myeloma. PMID- 26878613 TI - [Hypercalcemia related to PTH-rP revealing malignant hepatic epithelioid hemangioendothelioma]. AB - Hypercalcemia caused by tumor production of PTH-rp occurs most often in cases of squamous cell carcinoma of the lung, aerodigestive tract cancer, gynecological cancer and lymphoma. We report an exceptional case of PTH-rp related to a hepatic hemangioendothelioma. A 70 years-old male admitted for deterioration of the general state. The laboratory investigations revealed hypercalcemia, related to tumor production of PTH-rp. Imaging revealed tumoral hepatic lesions. Histopathological study and immunohistochemistry showed diffuse response for CD31 marker, CK20 (+) with CK7 (-) and hepatocyt antigen (-). The diagnosis of PTH-rp related to hepatic hemangioendothelioma was make. The patient died with recurrence of fatal hypercalcemia. Management of patients presenting with humoral hypercalcemia includes a vigorous search for tumor lesions. Elevated PTH-rp can be a bad prognostic factor. In front of tumoral liver lesions, a hepatic epithelioid hemangioendothelioma must be considered. Immunohistochemistry is necessary to make diagnosis. PMID- 26878615 TI - [Acquired Pelger-Huet anomaly/abnormal chromatin clumping of granulocytes after allogeneic hematopoietic stem cell transplantation for acute myeloid leukaemia: medication or relapse? ]. AB - An acute myeloid leukemia was diagnosed in a 53-year-old female patient. She received an allogeneic stem cell transplant. After this transplant, some neutrophils with hyposegmented nucleus and abnormal chromatin clumping appeared in the peripheral blood, and their number gradually increased. The hypothesis of early relapse after transplant was ruled out and drug-related anomaly was suspected. The authors discuss about morphological features of constitutional and acquired Pelger-Huet anomaly. In the patient reported here, ciclosporine seemed to be involved in the phenomenon, as the morphological anomaly of the neutrophils gradually decreased after the drug was discontinued. PMID- 26878616 TI - [Corynebacterium ulcerans pulmonary infection]. AB - Corynebacterium ulcerans is a bacterium able to infect humans by inducing a disease close to diphtheria. We describe the case of a 83-year-old patient hospitalized as a matter of urgency in intensive care for which C. ulcerans was isolated in pure culture in its bronchial samples. Even if the isolate was not secreting toxin in vitro, it possesses the tox gene which motivated the use of specific antitoxin serum. After two months of intensive care the patient went out of the service. It is about a remarkable case of clinicobiologic collaboration. PMID- 26878617 TI - Parasites and fungi as risk factors for human and animal health. AB - Recent literature data suggests that parasitic and fungal diseases, which pose a threat to both human and animal health, remain a clinical, diagnostic and therapeutic problem. Attention is increasingly paid to the role played by natural microbiota in maintaining homeostasis in humans. A particular emphasis is placed on the possibility of manipulating the human microbiota (permanent, transient, pathogenic) and macrobiota (e.g., Trichuris suis) to support the treatment of selected diseases such as Crohn's disease, obesity, diabetes and cancer. Emphasis is placed on important medical species whose infections not only impair health but can also be life threatening, such as Plasmodium falciparum, Echinococcus multilocularis and Baylisascaris procyonis, which expand into areas which have so far been uninhabited. This article also presents the epidemiology, diagnosis and treatment of opportunistic parasitoses imported from the tropics, which spread across large groups of people through human-to-human transmission (Enterobius vermicularis, Sarcoptes scabiei). It also discusses the problem of environmentally-conditioned parasitoses, particularly their etiological factors associated with food contaminated with invasive forms (Trichinella sp., Toxoplasma gondii). The analysis also concerns the presence of developmental forms of geohelminths (Toxocara sp.) and ectoparasites (ticks), which are vectors of serious human diseases (Lyme borreliosis, anaplasmosis, babesiosis), in the environment. Mycological topics contains rare cases of mycoses environmentally conditioned (CNS aspergillosis) and transmissions of these pathogens in a population of hospitalized individuals, as well as seeking new methods used to treat mycoses. PMID- 26878618 TI - The role of particular tick developmental stages in the circulation of tick-borne pathogens affecting humans in Central Europe. 1. The general pattern. AB - Tick-borne pathogens are common in the natural environment, but their occurrence has a focal character. They occur in the natural environment in the form of the enzootic sources of infection. The general components include the animal reservoir, amplifiers and the efficient vector. However, the particular role of components can differ depending on the pathogen, the host range and possible transmission routes. Animal reservoir of pathogen are vertebrate animals, being the hosts of pathogens. In Europe these are small or medium-sized mammals and sometimes birds that feed on the ground. The competence of an animal reservoir is determined by the ability to communicate the infection; long-term persistence of the pathogen in the host; long-duration of infectivity of the animal for ticks; a sufficient number of animals in the endemic region. Amplifiers for ticks are artiodactyls. They are hosts for nymphs and adult ticks, thereby making it possible for ticks to propagate and maintain the proper size of their population. Efficient vector for pathogen are ticks. The first characteristic feature of efficient vectors is feeding duration exceeding 24 hours; the high density of the tick population. The conditions necessary to consider ticks as efficient vectors are met in Central Europe by the Ixodes ricinus, Dermacentor reticulatus and D. marginatus ticks. There are the general differences in biology between Ixodes persulcatus complex ticks and Dermacentor ticks, affecting their different role and ability in pathogens spreading - the range of hosts; the ability to inhabiting of various environments and resistance to unfavourable conditions; the duration of larvae and nymphs activity. The combination of tick's biology, pathogen ability to transmission, and mammal hosts' competence, determines the particular role of larvae, nymphs and adults in pathogen circulation in the natural environment, as well as transmission to new hosts. PMID- 26878619 TI - Microparasites of worldwide mullets. AB - The present review is focus on parasitic organisms, previously considered as protozoans. Viral, prokaryotic and fungal parasites caused diseases and disorders of worldwide mullets were also observed. Most of the known viruses associated with a high mortality of mullets were detected in Mugil cephalus. Prokaryotic microparasites were registered in M. cephalus, Moolgarda cunnesiu, Liza ramada and Mugil liza. Fungal pathogens were associated with representatives of the genera Aphanomyces, Achlya, Phialemonium, Ichthyophonus. Ichthyophonus sp. can be considered as a potential threat for marine fish aquaculture, especially in culture conditions. A new hyperparasitic microsporidium like organism was recorded in myxozoan Myxobolus parvus infecting grey mullet Liza haematocheilus in the Russian coastal zone of the Sea of Japan. The protozoan representatives of the phyla Dinoflagellata, Euglenozoa, Ciliophora and Apicomplexa were reviewed and analyzed. The review of myxosporean parasites from grey mullets includes 64 species belonging to 13 genera and 9 families infecting 16 fish species PMID- 26878620 TI - Molecular characterization of the first internal transcribed spacer of rDNA of Parabronema skrjabini for the first time in sheep. AB - Parabronema skrjabini is a spirurid nematode of the family Habronematidae that lives in the abomasum of ruminants such as sheep and goats. The purpose of this study was to investigate the molecular aspects of Parabronema skrjabini in sheep. The worms were collected from sheep in Sanandaj (west of Iran). The first internal transcribed spacer (ITS) of ribosomal DNA (rDNA) nucleotide fragments of Parabronema skrjabini were amplified by polymerase chain reaction (PCR) using two pairs of specific primers (Para-Ir-R and Para-Ir-F). ITS1 homology in the sequence of this study was 69% compared with the sequence data in GenBank. To our knowledge, this is the first study in the world exploring the genetic diversity of P. skrjabini in sheep based on ITS1. PMID- 26878621 TI - Buxtonella spp. like infection in cattle in Sanandaj province, Iran. AB - Buxtonellosis is a disease caused by the ciliated protozoan Buxtonella sulcata (Jameson, 1926). B. sulcata is a common protozoan of ruminants and may result in subclinical infection or clinical disease including diarrhea. This study examined the prevalence of B. sulcata in cattle from Sanadaj province, Iran. Faecal samples were collected from cattle in the province from May 2013 to June 2014. A total of 217 cattle were selected randomly according to the age, sex, health, management system and season. In total, 99 cattle (45.63%) were found to be infected with B. sulcata. In adults, prevalence of B. sulcata infection (51.64%) was higher than calves (28.58%) and young cattle (40.55%). The prevalence of B. sulcata infection was also found to be higher in female (47.32%) than male (38.46) cattle. B. sulcata infection was significantly (p<0.05) higher in poor health cattle (body condition and weight) (79.54%) than healthy cattle (24.47%). This study demonstrates that cattle are highly susceptible to B. sulcata infection under a variety of housing and environmental conditions in this region of Iran. The study also demonstrates a significant effect of infection on cattle health. PMID- 26878622 TI - Zatorska goose - a subject of parasitological research. AB - The aim of the study was to determine the level of gastrointestinal parasites in a native breed of geese - Zatorska goose - based on coproscopic testing. Faecal samples were collected from 90 young geese in three age groups (5, 7 and 9 weeks old) in 2014. The geese were kept indoors on deep litter and pastured from spring to autumn. The area of the pastures around the buildings where the geese grazed was about 1 hectare, divided into quarters for different age groups. Before grazing, the birds were dewormed with fenbendazole (Fenbenat powder 4%, Naturan). As additional treatment for coccidiosis, coccidiostats were added to the feed. The study was conducted using the McMaster quantitative method with centrifugation (flotation liquid: NaCl and glucose). The birds were shown to be infected with coccidia and nematodes. The prevalence of Eimeria sp. infection (mean 40%) and the number of oocysts per gram of faeces (reaching 5,300 OPG) were highest in the youngest age group of geese. The level of Amidostomum anseris infection was similar in the three age groups, with prevalence from 40% to 50% (nematode egg output ranged from 50 to 350 eggs per gram of faeces, EPG). Capillaria anatis was observed only in 5- and 7-week-old geese. PMID- 26878623 TI - The Alice - "Follow the White Rabbit" - parasites of farm rabbits based on coproscopy. AB - The aim of the study, conducted in the years 2011-2013, was to determine the level of gastrointestinal parasites infection in New Zealand White rabbits, kept at the Experimental Station of the University of Agriculture in Krakow. The study showed rabbits protozoan infection with the genus Eimeria, belonging - based on the sporulation method - to the following species: E. magna, E. media, E. perforans, E. stiedae and E. irresidua. The highest prevalence of infection, as well as the intensity of oocysts output (OPG - oocysts per gram of faeces), was noted for E. magna and E. media - respectively 31.4 % (19477.3 OPG), and 40.0 % (14256.07 OPG). The infection of rabbits with Eimeria spp. differed significantly between years. With regard to oocysts output, the level of infection was strongly connected with the age of rabbits, being higher in young animals. However, the range of infection was highest among adults. Among nematodes, Passalurus ambiguus pinworm was regularly found (prevalence reached 21.9%), other species - Trichuris leporis, and Graphidium strigosum were rarely noted. The overall infection with nematodes did not differ between years. Similarly, as in the case of Eimeria older individuals were more often infected by nematodes. We observed some trends in parasite oocysts/eggs output; the protozoan oocysts were recorded more often in faecal samples collected in the evenings, whereas the nematodes eggs occurred frequently in the mornings. This situation may be related to the phenomenon of coprophagy occurring in the mammals of Lagomorpha order. The results of the study indicate that especially coccidiosis constitute permanently throughout the years an important problem in the rabbitry examined. PMID- 26878624 TI - Low seroprevalence of Trypanosoma cruzi infection and chronic chagasic cardiomyopathy in a region with abundance of triatomine vectors in Yucatan Peninsula of Mexico. AB - The Yucatan Peninsula of Mexico is endemic with Chagas disease. The main vector responsible for Trypanosoma cruzi transmission is Triatoma dimidiata which is abundant in domestic, peridomestic and sylvan cycles. The abundance of vectors favours T. cruzi transmission and is a high risk for developing chronic chagasic cardiomyopathy (CCC). In the past 10 years, little information was available on parasite seroprevalence and the prevalence of CCC in the Yucatan Peninsula. In the present work, we studied two Mayan communities with a high abundance of T. dimidiata and a random serial sample of 233 patients with an altered electrocardiogram or cardiac failure admitted to the Regional Hospital. A homemade enzyme-linked immunosorbent assay and indirect immunofluorescence standardized techniques were used to detect anti-T. cruzi IgG. In addition, Mayan volunteers were monitored by electrocardiography. In the Mayan communities, 4.8% (3/63) subjects were positive for T. cruzi antibodies none of them presented electrocardiographic alterations, however in seronegative subjects were detected right or left ventricle hypertrophy in 25% (16/63). A remarkable finding was that 90% of the Mayan population recognized the vector and 65% of them had experienced contact with triatomines bites. At the Regional Hospital 0.42% (1/233) were positive for T. cruzi antibodies showing compatible diagnosis with CCC; the most frequent pathology in this population was hypertension in 65% (151/233) and the less frequent was dilated myocardiopathy 6% (14/233). In conclusion, the prevalence of T. cruzi infection and CCC can be considered low in Yucatan, Mexico. PMID- 26878625 TI - Molecular characterization and seroprevalence of Echinococcus granulosus in wild boars (Sus scrofa) in south-western Iran. AB - This study presents the first molecular and serological evaluation of Echinococcus granulosus infections in wild boars in Iran. Twenty five wild boars were collected in south-western Iran, during authorized hunting program, from March to October 2013, necropsied and examined for E. granulosus infection. Furthermore, seroprevalence of cystic echinococcosis in hunted boars was evaluated by an ELISA system. A fertile hydatid cyst due to E. granulosus was detected in the lung of one of the animals. Genotype analysis of the isolate was determined by analyzing a mitochondrial gene, cytochrome C oxidase subunit 1 (co1). DNA was extracted from the cyst sample and polymerase chain reaction amplification and DNA sequencing of the specific region of the co1 gene was performed. Molecular evaluation confirmed the presence of a sheep strain, the G1 genotype, in the wild boar in south-western Iran. This is the first report of the presence of G1 genotype of E. granulosus in wild boar in Iran. Serological evaluation of hydatid cyst by antigen-B ELISA revealed E. granulosus antibodies in 5 (20%) of 25 wild boars. A statistically significant difference was observed between the prevalence of E. granulosus antibodies and gender while the difference between the seroprevalence of E. granulosus and age was insignificant. Findings of this study might have important implications for the prevention and control of cystic echinococcosis. PMID- 26878626 TI - Intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt. AB - This cross-sectional study was carried to determine the prevalence of intestinal parasitic infections among mentally handicapped individuals in Alexandria, Egypt, in the period from December 2012 till November 2013. The study was conducted on 200 institutionalized and non-institutionalized mentally handicapped individuals. Fresh stool samples were subjected to different stains including; trichrome for detecting intestinal protozoa, modified acid fast stain for intestinal coccidia and quick hot gram chromotrope stain for Microsporidia. Also they were processed by Kato-Katz and formol ethyl acetate techniques for intestinal helminths. Additionally, blood samples were collected for measuring hemoglobin levels. Out of 200 mentally handicapped individuals, 87 (43.5%) were infected. The infection rates were 44.6% and 42.6% for non-institutionalized and institutionalized people, respectively. Regarding gender, 46.7% and 38.5% were reported for the males and females respectively. The most common parasites detected were: Cryptosporidium sp. (23.5%), microsporidia (15%), Giardia lamblia (8.5%), Dientamoeba fragilis (8%), Cyclospora cyatanensis (7.5%), Blastocystis hominis (6.5%), Entamoeba histolytica (5.5%) and Entamoeba coli (2.5%). Rates for Isospora belli and Enterobius vermicularis were estimated to be 1.5% for each, while lower rate was reported for Iodamoeba butschlii (1.0%). Prevalence of infections among mentally handicapped individuals are indications for several risk factors, including improper sanitary hygiene and illiteracy about personal hygiene. Therefore, frequent investigations, health care and medical intervention are needed. PMID- 26878627 TI - Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis). AB - Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals. PMID- 26878628 TI - New host records for parasitic mites of the family Syringophilidae from accipitriform birds (Aves: Accipitriformes). AB - Four accipitriform bird species of the family Accipitridae are reported as new hosts for quill mites (Acari: Cheyletoidea: Syringophilidae): Megasyringophilus aquilus Skoracki, Lontkowski and Stawarczyk, 2010 was collected from Hieraaetus pennatus Gmelin, 1788 in France and Spain, and Buteo jamaicensis Gmelin, 1788 in Canada; Peristerophila accipitridicus Skoracki, Lontkowski and Stawarczyk, 2010 was collected from Circaetus gallicus Gmelin, 1788 in France, and Buteo lagopus Pontoppidan, 1763 in Germany. PMID- 26878629 TI - Ocular cysticercosis with intermittent blindness. AB - We report this peculiar case of ocular cysticercosis with intermittent blindness which is never reported to our knowledge. This case highlights use of Ultrasound for examination of the posterior segment of eye globe. In limited facilities Ultrasound is the main modality to reach the diagnosis. We also wish to enforce the point that in endemic regions and in young population primary cysticercosis and its complications must be kept in differentials of cystic mass or calcified mass, as in this case, we have seen both the stages of cysticercosis progression. PMID- 26878630 TI - The Nobel Prize 2015 in physiology or medicine for highly effective antiparasitic drugs. PMID- 26878631 TI - Nobel Price 2015 for Dr William C. Campbell. PMID- 26878632 TI - Method for screening prevention and control measures and technologies based on groundwater pollution intensity assessment. AB - This paper presents a system for determining the evaluation and gradation indices of groundwater pollution intensity (GPI). Considering the characteristics of the vadose zone and pollution sources, the system decides which anti-seepage measures should be implemented at the contaminated site. The pollution sources hazards (PSH) and groundwater intrinsic vulnerability (GIV) are graded by the revised Nemerow Pollution Index and an improved DRTAS model, respectively. GPI is evaluated and graded by a double-sided multi-factor coupling model, which is constructed by the matrix method. The contaminated sites are categorized as prior, ordinary, or common sites. From the GPI results, we develop guiding principles for preventing and removing pollution sources, procedural interruption and remediation, and end treatment and monitoring. Thus, we can select appropriate prevention and control technologies (PCT). To screen the technological schemes and optimize the traditional analytical hierarchy process (AHP), we adopt the technique for order preference by the similarity to ideal solution (TOPSIS) method. Our GPI approach and PCT screening are applied to three types of pollution sites: the refuse dump of a rare earth mine development project (a potential pollution source), a chromium slag dump, and a landfill (existing pollution sources). These three sites are identified as ordinary, prior, and ordinary sites, respectively. The anti-seepage materials at the refuse dump should perform as effectively as a 1.5-m-thick clay bed. The chromium slag dump should be preferentially treated by soil flushing and in situ chemical remediation. The landfill should be treated by natural attenuation technology. The proposed PCT screening approach was compared with conventional screening methods results at the three sites and proved feasible and effective. The proposed method can provide technical support for the monitoring and management of groundwater pollution in China. PMID- 26878633 TI - Influences of the land use pattern on water quality in low-order streams of the Dongjiang River basin, China: A multi-scale analysis. AB - Understanding the relationships between land use patterns and water quality in low-order streams is useful for effective landscape planning to protect downstream water quality. A clear understanding of these relationships remains elusive due to the heterogeneity of land use patterns and scale effects. To better assess land use influences, we developed empirical models relating land use patterns to the water quality of low-order streams at different geomorphic regions across multi-scales in the Dongjiang River basin using multivariate statistical analyses. The land use pattern was quantified in terms of the composition, configuration and hydrological distance of land use types at the reach buffer, riparian corridor and catchment scales. Water was sampled under summer base flow at 56 low-order catchments, which were classified into two homogenous geomorphic groups. The results indicated that the water quality of low order streams was most strongly affected by the configuration metrics of land use. Poorer water quality was associated with higher patch densities of cropland, orchards and grassland in the mountain catchments, whereas it was associated with a higher value for the largest patch index of urban land use in the plain catchments. The overall water quality variation was explained better by catchment scale than by riparian- or reach-scale land use, whereas the spatial scale over which land use influenced water quality also varied across specific water parameters and the geomorphic basis. Our study suggests that watershed management should adopt better landscape planning and multi-scale measures to improve water quality. PMID- 26878634 TI - Sediment amino acids as indicators of anthropogenic activities and potential environmental risk in Erhai Lake, Southwest China. AB - Total hydrolysable amino acids (THAAs) constitute the most important fraction of labile nitrogen. Anthropogenic activities directly influence various biogeochemical cycles and then accelerate lake ecosystem deterioration. This is the first study that has established the relationship between sediment THAAs and anthropogenic activities using dated sediment cores, and evaluated the possibility of THAAs release at the sediment interface based on changes in environmental conditions in Erhai Lake. The results showed that historical distribution and fractions of THAAs could be divided into three stages: a stable period before the 1970s, a clear increasing period from the 1970s to 1990s, and a gradually steady period that started after the 1990s. The chemical fraction, aromatic and sulfur amino acids (AAs) accounted for only <=3% of THAAs. Basic AAs accounted for 5-17% of THAAs, and remained at a relatively stable level. However, acidic and neutral AAs, which accounted for 19-44% and 35-69% of THAAs, respectively, were the predominant factors causing THAAs to increase due to rapid agricultural intensification and intensification of contemporary sedimentation of phytoplankton or macrophytes since the 1970s. These trends were closely related to both anthropogenic activities and natural processes, which implied that sediment THAAs could act as an effective indicator that reflects anthropogenic activities and aquatic environmental characteristics. The current contributions of sediment THAAs on TN and TOC were <5% and 1.5%, respectively. However, the dramatic increase in THAAs in the sediment cores indicated that there was a huge potential source of labile nitrogen for the overlying water under certain environmental conditions. Correlation analysis suggested that the release of THAAs was negatively correlated with pH, whereas positively correlated with bacterial number and degree of OM mineralization, which particularly depend on the stability of HFOM. Therefore, the risk of sediment THAAs release might increase when the sediment environment continuously changes. PMID- 26878635 TI - Genotoxic and histopathological biomarkers for assessing the effects of magnetic exfoliated vermiculite and exfoliated vermiculite in Danio rerio. AB - Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects. PMID- 26878636 TI - Arsenic release from Floridan Aquifer rock during incubations simulating aquifer storage and recovery operations. AB - While aquifer storage and recovery (ASR) is becoming widely accepted as a way to address water supply shortages, there are concerns that it may lead to release of harmful trace elements such as arsenic (As). Thus, mechanisms of As release from limestone during ASR operations were investigated using 110-day laboratory incubations of core material collected from the Floridan Aquifer, with treatment additions of labile or refractory dissolved organic matter (DOM) or microbes. During the first experimental phase, core materials were equilibrated with native groundwater lacking in DO to simulate initial non-perturbed anaerobic aquifer conditions. Then, ASR was simulated by replacing the native groundwater in the incubations vessels with DO-rich ASR source water, with DOM or microbes added to some treatments. Finally, the vessels were opened to the atmosphere to mimic oxidizing conditions during later stages of ASR. Arsenic was released from aquifer materials, mainly during transitional periods at the beginning of each incubation stage. Most As released was during the initial anaerobic experimental phase via reductive dissolution of Fe oxides in the core materials, some or all of which may have formed during the core storage or sample preparation period. Oxidation of As-bearing Fe sulfides released smaller amounts of As during the start of later aerobic experimental phases. Additions of labile DOM fueled microbially-mediated reactions that mobilized As, while the addition of refractory DOM did not, probably due to mineral sorption of DOM that made it unavailable for microbial utilization or metal chelation. The results suggest that oscillations of groundwater redox conditions, such as might be expected to occur during an ASR operation, are the underlying cause of enhanced As release in these systems. Further, ASR operations using DOM-rich surface waters may not necessarily lead to additional As releases. PMID- 26878637 TI - Sn(II) oxy-hydroxides as potential adsorbents for Cr(VI)-uptake from drinking water: An X-ray absorption study. AB - The feasibility of implementing a Sn(II) oxy-hydroxide (Sn6O4(OH)4) for the reduction and adsorption of Cr(VI) in drinking water treatment was investigated using XAFS spectroscopies at the Cr-K-edge. The analysis of the Cr-K-edge XANES and EXAFS spectra verified the effective use of Sn6O4(OH)4 for successful Cr(VI) removal. Adsorption isotherms, as well as dynamic Rapid Small Scale Test (RSSCT) in NSF water matrix showed that Sn6O4(OH)4 can decrease Cr(VI) concentration below the upcoming regulation limit of 10MUg/L for drinking water. Moreover, an uptake capacity of 7.2MUg/mg at breakthrough concentration of 10MUg/L was estimated from the RSSCT, while the residual Cr(VI) concentration ranged at sub ppb level for a significant period of the experiment. Furthermore, no evidence for the formation of Cr(OH)3 precipitates was found. On the contrary, Cr(III) oxyanions were chemisorbed onto SnO2, which was formed after Sn(II)-oxidation during Cr(VI)-reduction. Nevertheless, changes in the type of Cr(III)-inner sphere complexes were observed after increasing surface coverage: Cr(III) oxyanions preferentially sorb in a geometry which combines both bidentate binuclear ((2)C) and monodentate ((1)V) geometries, at the expense of the present bidentate mononuclear ((2)E) contributions. On the other hand, the pH during sorption does not affect the adsorption mechanism of Cr(III)-species. The implementation of Sn6O4(OH)4 in water treatment technology combines the advantage of rapidly reducing a large amount of Cr(VI) due to donation of two electrons by Sn(II) and also the strong chemisorption of Cr(III) in a combination of the (2)C and (1)V configurations, which enhances the safe disposal of spent adsorbents. PMID- 26878638 TI - Greenhouse gases from wastewater treatment - A review of modelling tools. AB - Nitrous oxide, carbon dioxide and methane are greenhouse gases (GHG) emitted from wastewater treatment that contribute to its carbon footprint. As a result of the increasing awareness of GHG emissions from wastewater treatment plants (WWTPs), new modelling, design, and operational tools have been developed to address and reduce GHG emissions at the plant-wide scale and beyond. This paper reviews the state-of-the-art and the recently developed tools used to understand and manage GHG emissions from WWTPs, and discusses open problems and research gaps. The literature review reveals that knowledge on the processes related to N2O formation, especially due to autotrophic biomass, is still incomplete. The literature review shows also that a plant-wide modelling approach that includes GHG is the best option for the understanding how to reduce the carbon footprint of WWTPs. Indeed, several studies have confirmed that a wide vision of the WWPTs has to be considered in order to make them more sustainable as possible. Mechanistic dynamic models were demonstrated as the most comprehensive and reliable tools for GHG assessment. Very few plant-wide GHG modelling studies have been applied to real WWTPs due to the huge difficulties related to data availability and the model complexity. For further improvement in GHG plant-wide modelling and to favour its use at large real scale, knowledge of the mechanisms involved in GHG formation and release, and data acquisition must be enhanced. PMID- 26878639 TI - Risk assessment of urban soils contamination: The particular case of polycyclic aromatic hydrocarbons. AB - The assessment of soil quality and characterization of potential risks to the environment and human health can be a very difficult task due to the heterogeneity and complexity of the matrix, the poor understanding about the fate of contaminants in the soil matrix, scarcity of toxicological/ecotoxicological data and variability of guidelines. In urban soils these difficulties are enhanced by the patchy nature of urban areas and the presence of complex mixtures of organic and inorganic contaminants resulting from diffuse pollution caused by urban activities (e.g. traffic, industrial activity, and burning of carbon sources for heating). Yet, several tools are available which may help to assess the risks of soil contamination in a simpler, cost effective and reliable way. Within these tools, a tiered risk assessment (RA) approach, first based on a chemical screening in combination with geostatistical tools, may be very useful in urban areas. However, there is still much to improve and a long way to go in order to obtain a reliable RA, especially in the case of hydrophobic organic compounds such as polycyclic aromatic hydrocarbons (PAHs). This paper aims at proposing a RA framework to assess the environmental and human health risks of PAHs present in urban soils, based on existing models. In addition, a review on ecotoxicological, toxicological, and exposure assessment data was made, as well as of the existing soil quality guidelines for PAHs that can be used in the RA process. PMID- 26878640 TI - Persistent organic pollutants and pregnancy complications. AB - We sought to investigate the relationship between maternal preconception exposures to persistent organic pollutants (POPs) and pregnancy complications, gestational diabetes (GDM) and gestational hypertension. Data from 258 (51%) women with human chorionic gonadotropin (hCG) confirmed pregnancies reaching >=24weeks gestation, from a prospective cohort of 501 couples who discontinued contraception to attempt pregnancy, were analyzed. Preconception concentrations of 9 organochlorine pesticides (OCPs) and 10 polybrominated diphenyl ethers (PBDEs) were quantified in serum. In separate multiple logistic regression models of self-reported physician diagnosed outcomes: GDM (11%) and gestational hypertension (10%), chemicals were natural log-transformed and rescaled by their standard deviation (SD). Models were adjusted for serum lipids, and then adjusted for age, body mass index, race, and smoking. Models were additionally adjusted for the sum of the remaining POPs in each chemical class. Women's serum concentration of PBDE congener 153 (PBDE-153) was positively associated with an increased odds of GDM per SD increase in log-transformed concentration, for unadjusted (OR=1.36, 95%CI: 1.02-1.81), a priori adjusted (OR=1.38, 95% CI: 1.03 1.86) and with the sum of remaining PBDEs (OR=1.79, 95% CI: 1.18, 2.74) models. Our findings suggest that at environmentally relevant concentrations, maternal exposure to POPs prior to conception may contribute to increased chance of developing GDM. PMID- 26878641 TI - Climatology and trends of aerosol optical depth over the Mediterranean basin during the last 12years (2002-2014) based on Collection 006 MODIS-Aqua data. AB - The Mediterranean basin is a region of particular interest for studying atmospheric aerosols due to the large variety of air masses it receives, and its sensitivity to climate change. In this study we use the newest collection (C006) of aerosol optical depth from MODIS-Aqua, from which we also derived the fine mode fraction and Angstrom exponent over the last 12years (i.e., from 2002 to 2014), providing the longest analyzed dataset for this region. The long-term regional optical depth average is 0.20+/-0.05, with the indicated uncertainty reflecting the inter-annual variability. Overall, the aerosol optical depth exhibits a south-to-north decreasing gradient and an average decreasing trend of 0.0030 per year (19% total decrease over the study period). The correlation between the reported AOD observations with measurements from the ground AERONET stations is high (R=0.76-0.80 depending on the wavelength), with the MODIS-Aqua data being slightly overestimated. Both fine-fraction and Angstrom exponent data highlight the dominance of anthropogenic aerosols over the northern, and of desert aerosols over the southern part of the region. Clear intrusions of desert dust over the Eastern Mediterranean are observed principally in spring, and in some cases in winter. Dust intrusions dominate the Western Mediterranean in the summer (and sometimes in autumn), whereas anthropogenic aerosols dominate the sub region of the Black Sea in all seasons but especially during summer. Fine-mode optical depth is found to decrease over almost all areas of the study region during the 12-year period, marking the decreasing contribution of anthropogenic particulate matter emissions over the study area. Coarse-mode aerosol load also exhibits an overall decreasing trend. However, its decrease is smaller than that of fine aerosols and not as uniformly distributed, underlining that the overall decrease in the region arises mainly from reduced anthropogenic emissions. PMID- 26878642 TI - The metabolite 3,4,3',4'-tetrachloroazobenzene (TCAB) exerts a higher ecotoxicity than the parent compounds 3,4-dichloroaniline (3,4-DCA) and propanil. AB - 3,4,3',4'-tetrachloroazobenzene (TCAB) is not commercially manufactured but formed as an unwanted by-product in the manufacturing of 3,4-dichloroaniline (3,4 DCA) or metabolized from the degradation of chloranilide herbicides, like propanil. While a considerable amount of research has been done concerning the toxicological and ecotoxicological effects of propanil and 3,4-DCA, limited information is available on TCAB. Our study examined the toxicity of TCAB in comparison to its parent compounds propanil and 3,4-DCA, using a battery of bioassays including in vitro with aryl hydrocarbon receptor (AhR) mediated activity by the 7-ethoxyresorufin-O-deethylase (EROD) assay and micro-EROD, endocrine-disrupting activity with chemically activated luciferase gene expression (CALUX) as well as in vivo with fish embryo toxicity (FET) assays with Danio rerio. Moreover, the quantitative structure activity response (QSAR) concepts were applied to simulate the binding affinity of TCAB to certain human receptors. It was shown that TCAB has a strong binding affinity to the AhR in EROD and micro-EROD induction assay, with the toxic equivalency factor (TEF) of 8.7*10(-4) and 1.2*10(-5), respectively. TCAB presented to be a weak endocrine disrupting compound with a value of estradiol equivalence factor (EEF) of 6.4*10( 9) and dihydrotestosterone equivalency factor (DEF) of 1.1*10(-10). No acute lethal effects of TCAB were discovered in FET test after 96h of exposure. Major sub-lethal effects detected were heart oedema, yolk malformation, as well as absence of blood flow and tail deformation. QSAR modelling suggested an elevated risk to environment, particularly with respect to binding to the AhR. An adverse effect potentially triggering ERbeta, mineralocorticoid, glucocorticoid and progesterone receptor activities might be expected. Altogether, the results obtained suggest that TCAB exerts a higher toxicity than both propanil and 3,4 DCA. This should be considered when assessing the impact of these compounds for the environment and also for regulatory decisions. PMID- 26878644 TI - Methyl chloride and methyl bromide emissions from baking: an unrecognized anthropogenic source. AB - Methyl chloride and methyl bromide (CH3Cl and CH3Br) are the largest natural sources of chlorine and bromine, respectively, to the stratosphere, where they contribute to ozone depletion. We report the anthropogenic production of CH3Cl and CH3Br during breadbaking, and suggest this production is an abiotic process involving the methyl ester functional groups in pectin and lignin structural polymers of plant cells. Wide variations in baking styles allow only rough estimates of this flux of methyl halides on a global basis. A simple model suggests that CH3Br emissions from breadbaking likely peaked circa 1990 at approximately 200tonnes per year (about 0.3% of industrial production), prior to restrictions on the dough conditioner potassium bromate. In contrast, CH3Cl emissions from breadbaking may be of similar magnitude as acknowledged present day CH3Cl industrial emissions. Because the mechanisms involve functional groups and compounds widely found in plant materials, this type of methyl halide production may occur in other cooking techniques as well. PMID- 26878643 TI - The impact of built-up surfaces on land surface temperatures in Italian urban areas. AB - Urban areas are characterized by the very high degree of soil sealing and continuous built-up areas: Italy is one of the European countries with the highest artificial land cover rate, which causes a substantial spatial variation in the land surface temperature (LST), modifying the urban microclimate and contributing to the urban heat island effect. Nevertheless, quantitative data regarding the contribution of different densities of built-up surfaces in determining urban spatial LST changes is currently lacking in Italy. This study, which aimed to provide clear and quantitative city-specific information on annual and seasonal spatial LST modifications resulting from increased urban built-up coverage, was conducted generally throughout the whole year, and specifically in two different periods (cool/cold and warm/hot periods). Four cities (Milan, Rome, Bologna and Florence) were included in the study. The LST layer and the built-up surface indicator were obtained via use of MODIS remote sensing data products (1km) and a very high-resolution map (5m) of built-up surfaces recently developed by the Italian National Institute for Environmental Protection and Research. The relationships between the dependent (mean daily, daytime and nighttime LST values) and independent (built-up surfaces) variables were investigated through linear regression analyses, and comprehensive built-up-surface-related LST maps were also developed. Statistically significant linear relationships (p<0.001) between built-up surfaces and spatial LST variations were observed in all the cities studied, with a higher impact during the warm/hot period than in the cool/cold ones. Daytime and nighttime LST slope patterns depend on the city size and relative urban morphology. If implemented in the existing city plan, the urban maps of built-up-surface-related LST developed in this study might be able to support more sustainable urban land management practices by identifying the critical areas (Hot-Spots) that would benefit most from mitigation actions by local authorities, land-use decision makers, and urban planners. PMID- 26878645 TI - Tissue distribution of zinc and subtle oxidative stress effects after dietary administration of ZnO nanoparticles to rainbow trout. AB - The increasing use of ZnO nanoparticles (ZnO NPs) in different fields has raised concerns about the possible environmental risks associated with these NPs entering aquatic systems. In this study, using a dietary exposure route, we have analysed the tissue distribution and depuration pattern of Zn as well as any associated redox balance disturbances in rainbow trout (Oncorhynchus mykiss) following exposure to ZnO NPs (20-30nm). Fish were fed a diet spiked with ZnO NPs prepared from a dispersion in sunflower oil at doses of 300 or 1000mg ZnO NPs/kg feed for 10days. This uptake phase was followed by a 28days depuration phase in which fish from all groups received untreated feed. While no overt signs of toxicity were observed and no important effects in fish growth (weight and length) or in the hepatosomatic index among groups were recorded, we observed high levels of Zn bioaccumulation in the gills and intestine of exposed fish following exposure to both dose levels. Zn levels were not eliminated during the depuration phase and we have evidenced oxidative stress responses in gills associated with such long term ZnO NPs bioaccumulation and lack of elimination. Furthermore, exposures to higher doses of ZnO NPs (1000mg/kg feed) resulted in Zn distribution to the liver of fish following 10days of exposure. Fish from this exposure group experienced biochemical disturbances associated with oxidative stress in the liver and ethoxy-resorufin-O-deethylase (EROD) activity which may point to the ability of ZnO NPs or its ions to interfere with cytochrome P450 metabolic processes. PMID- 26878646 TI - Maternal and early life exposure to phthalates: The Plastics and Personal-care Products use in Pregnancy (P4) study. AB - Phthalates are a group of chemicals found in a number of consumer products; some of these phthalates have been shown to possess estrogenic activity and display anti-androgenic effects. While a number of biomonitoring studies of phthalates in pregnant women and infants have been published, there is a paucity of data based on both multiple sampling periods and in different matrices. Phthalate metabolites were measured in 80 pregnant women and their infants in Ottawa Canada (2009-2010) in urine, meconium and breast milk collected at various time periods pre- and post-parturition. At least 50% of the women had at least one urine sample greater than the limit of detection (LOD) for the various phthalate metabolites, with the exception of mono-n-octyl phthalate (MnOP), mono-isononyl phthalate (MiNP) and mono(carboxy-isooctyl) phthalate (MCiOP). Four major clusters of maternal urinary metabolites were identified. Among infants (n=61), the following metabolites were rarely (< 10%) detected: mono-cyclohexyl phthalate (MCHP), mono-isononyl phthalate (MiNP), mono-methyl phthalate (MMP), and mono-n octyl phthalate (MnOP). While mono-benzyl phthalate (MBzP), mono-3-carboxypropyl phthalate (MCPP), MEHHP, and MEOHP were frequently detected in maternal urines at any time point, these metabolites were rarely detected in breast milk. Maternal urinary concentrations of MEP and the DEHP metabolites were higher in samples collected during pregnancy than postnatally. No statistically significant differences were observed in infant's urinary phthalate concentrations between breast-fed and bottle-fed infants. Significant correlations were observed between maternal urinary MEHHP (r=0.35), MEOHP (r=0.35) and MEP (r=0.37) collected at <20weeks gestation with levels in meconium and between MBzP (r=0.78) and MEP (r=0.56) in maternal and infant urine collected 2-3months after birth. These results suggest at least some maternal-fetal-infant transfer of phthalates and that meconium may be a useful matrix for measuring in utero exposure to phthalates. PMID- 26878647 TI - Effect of CCL2 on BV2 microglial cell migration: Involvement of probable signaling pathways. AB - Microglia, the resident macrophages of the central nervous system, play a vital role in the regulation of innate immune function and neuronal homeostasis of the brain. Currently, much interest is being generated regarding the investigation of the microglial migration that results in their accumulation at focal sites of injury. Chemokines including CCL2 are known to cause the potential induction of migration of microglial cells, although the underlying mechanisms are not well understood. In the present study, using murine neonatal BV2 microglial cells as a model, we investigate the impact of CCL2 on the migration of microglial cells and address the probable molecular events within the cellular signaling cascades mediating CCL2-induced cell migration. Our results demonstrate concentration- and time-dependent induction of BV2 cell migration by CCL2 and reveal complex mechanisms involving the activation of MEK, ERK1/2, and Akt, and their cross talk. In addition, we demonstrate that the MEK/ERK pathway activated by CCL2 treatment mediate p90RSK activation in BV2 cells. Moreover, our findings indicate that Akt, ERK1/2, and p90RSK are the downstream effectors of PI3K in the CCL2 induced signaling. Finally, phosphorylation of the transcription factors c-jun and ATF-1 is found to be a further downstream signaling cascade in the CCL2 mediated action. Our results suggest that CCL2-induced activation of c-jun and ATF-1 is likely to be linked to the MEK/ERK and PI3K signaling pathways, respectively. Taken together, these findings contribute to a better understanding of CCL2-induced microglial migration and the probable signaling pathways involved. PMID- 26878649 TI - High IL-6 and low IL-15 levels mark the presence of TB infection: A preliminary study. AB - The host immune response, apart from mycobacterial factors, is a significant determinant in the development of tuberculosis (TB). The purpose of the study was to examine whether the differential serum profiles of cytokines IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-15, IFN-gamma, TGF-beta, and TNF-alpha could discriminate between TB patients and healthy controls and provide insights into pathogenesis. Serum samples from TB patients, TB patient contacts and healthy controls were collected and analyzed by ELISA. The cytokine concentrations obtained were stratified into three groups: below detection limit (BDL), low values, and high values. The differences in cytokine concentrations were analyzed by Fisher's exact test. The statistically significant results were interpreted based on post hoc analysis of the chi square contingency table using the adjusted residual method. Among the assayed cytokines, there was a statistically significant difference in the detection levels of IL-6, IL-15 and IFN-gamma. Levels of IL 1beta, IL-2, IL-4, IL-10, TGF-beta and TNF-alpha did not vary. Post-hoc analysis of the significant results revealed that dynamic changes in the BDL and high values of cytokines influenced the post-infection cytokine milieu in the study subjects. The study concludes that altered balance in the levels of serum cytokines can be indicative of TB pathogenesis. Hence, profiling of dynamic changes in cytokines would facilitate effective TB diagnostic and treatment strategies. PMID- 26878648 TI - Host biomarkers detected in saliva show promise as markers for the diagnosis of pulmonary tuberculosis disease and monitoring of the response to tuberculosis treatment. AB - BACKGROUND: There is an urgent need for new tools for the rapid diagnosis of tuberculosis (TB) disease in resource-constrained settings. Tests based on host immunological biomarkers maybe useful, especially if based on easily available samples. We investigated host biomarkers detected in saliva samples from individuals with suspected pulmonary TB disease, as tools for the diagnosis of TB disease and monitoring of the response to treatment. METHODS: We collected saliva samples from 104 individuals that presented with symptoms requiring investigation for TB disease at a primary health care clinic in the outskirts of Cape Town, South Africa, prior to assessment for TB disease. We evaluated the concentrations of 33 host markers in stored saliva samples using a multiplex cytokine platform. Using a combination of clinical, radiological and laboratory results and a pre established diagnostic algorithm, participants were later classified as having TB disease or other respiratory diseases (ORD). The diagnostic potentials of individual analytes were analysed by the receiver operator characteristics curve approach while the predictive abilities of combinations of analytes for TB disease were analysed by general discriminant analysis, with leave-one-out cross validation. RESULTS: Of the 104 individuals enrolled, 32 were pulmonary TB cases. There were significant differences in the levels of 10 of the markers investigated between the patients with TB disease and those with ORDs. However, the optimal diagnostic biosignature was a seven-marker combination of salivary CRP, ferritin, serum amyloid P, MCP-1, alpha-2-macroglobulin, fibrinogen and tissue plasminogen activator. This biosignature diagnosed TB disease with a sensitivity of 78.1% (95% CI, 59.6-90.1%) and specificity of 83.3% (95% CI, 72.3 90.7%) after leave-one-out cross validation. When compared to baseline levels, the concentrations of 9 markers including granzyme A, MCP-1, IL-1beta, IL-9, IL 10, IL-15, MIP-1beta, ferritin and serum amyloid A changed significantly by months 2 or 6 after initiation of TB treatment, thereby indicating that they might be useful in monitoring the response to TB treatment. CONCLUSION: We have identified candidate biomarkers in saliva, which may be useful in the diagnosis of TB disease and monitoring of the response to TB treatment. These results require further validation in larger studies. PMID- 26878650 TI - Application of first order kinetics to characterize MTBE natural attenuation in groundwater. AB - Methyl tertiary butyl ether (MTBE) was a gasoline oxygenate that became widely used in reformulated gasoline as a means to reduce air pollution in the 1990s. Unfortunately, many of the underground storage tanks containing reformulated gasoline experienced subsurface releases which soon became a health concern given the increase in public and private water supplies containing MTBE. Many states responded to this by banning the use of MTBE as an additive, including Connecticut. Although MTBE dissipates by natural attenuation, it continues to be prevalent in groundwater long after the Connecticut ban in 2004. This study estimated the rate of the natural attenuation in groundwater following the Connecticut ban by evaluating the MTBE concentration two years prior to and two years after the MTBE ban at eighty-three monitoring wells from twenty-two retail gasoline stations where MTBE contamination was observed. Sites chosen for this study had not undergone active remediation ensuring no artificial influence to the natural attenuation processes that controls the migration and dissipation of MTBE. Results indicate that MTBE has dissipated in the natural environment, at more than 80% of the sites and at approximately 82% of the individual monitoring wells. In general, dissipation approximated first order kinetics. Dissipation half-lives, calculated using concentration data from the two year period after the ban, ranged from approximately three weeks to just over seven years with an average half-life of 7.3 months with little variability in estimates for different site characteristics. The accuracy of first order estimates to predict further MTBE dissipation were tested by comparing predicted concentrations with those observed after the two year post-ban period; the predicted concentrations closely match the observed concentrations which supports the use of first order kinetics for predictions of this nature. PMID- 26878651 TI - Analysis of the temperature sensitivity of Japanese rubella vaccine strain TO 336.vac and its effect on immunogenicity in the guinea pig. AB - The marker of Japanese domestic rubella vaccines is their lack of immunogenicity in guinea pigs. This has long been thought to be related to the temperature sensitivity of the viruses, but supporting evidence has not been described. In this study, we generated infectious clones of TO-336.vac, a Japanese domestic vaccine, TO-336.GMK5, the parental virus of TO-336.vac, and their mutants, and determined the molecular bases of their temperature sensitivity and immunogenicity in guinea pigs. The results revealed that Ser(1159) in the non structural protein-coding region was responsible for the temperature sensitivity of TO-336.vac dominantly, while the structural protein-coding region affected the temperature sensitivity subordinately. The findings further suggested that the temperature sensitivity of TO-336.vac affected the antibody induction in guinea pigs after subcutaneous inoculation. PMID- 26878652 TI - vwF A3-GPI modification of EPCs accelerates reendothelialization of injured vessels via collagen targeting in mice. AB - Despite the potential of endothelial progenitor cells (EPCs) to incorporate into sites of vessel injury and differentiate into endothelial cells, thereby contributing to the improvement of endothelial function, reendothelialization in some patients is insufficient for the prevention of abnormal endothelial growth because there is a lack of specific guided signals and low levels of congregation of the EPCs to the injured areas. If some type of molecular tool was able to guide EPCs specifically to the injured vessels, however, then the efficacy of cell implantation would improve. Here, we designed a strategy to modify these cells and improve their ability to directly target the injured vessels. As a homing molecule, we selected extracellular matrix components, such as collagen, which is exposed on catheter-injured arteries. To promote the adhesion of the EPCs to collagen, we painted the primary EPCs with a recombinant, glycosylphosphatidylinositol (GPI)-linked high-affinity ligand for collagen that is termed von Willebrand factor A3-GPI. These painted EPCs specifically bound to collagen in vitro and traveled to the damaged vessel in vivo. This novel strategy may allow for significant advancements in EPCs transplantation treatment. PMID- 26878653 TI - Real-time prediction and gating of respiratory motion in 3D space using extended Kalman filters and Gaussian process regression network. AB - The prediction as well as the gating of respiratory motion have received much attention over the last two decades for reducing the targeting error of the radiation treatment beam due to respiratory motion. In this article, we present a real-time algorithm for predicting respiratory motion in 3D space and realizing a gating function without pre-specifying a particular phase of the patient's breathing cycle. The algorithm, named EKF-GPRN(+) , first employs an extended Kalman filter (EKF) independently along each coordinate to predict the respiratory motion and then uses a Gaussian process regression network (GPRN) to correct the prediction error of the EKF in 3D space. The GPRN is a nonparametric Bayesian algorithm for modeling input-dependent correlations between the output variables in multi-output regression. Inference in GPRN is intractable and we employ variational inference with mean field approximation to compute an approximate predictive mean and predictive covariance matrix. The approximate predictive mean is used to correct the prediction error of the EKF. The trace of the approximate predictive covariance matrix is utilized to capture the uncertainty in EKF-GPRN(+) prediction error and systematically identify breathing points with a higher probability of large prediction error in advance. This identification enables us to pause the treatment beam over such instances. EKF GPRN(+) implements a gating function by using simple calculations based on the trace of the predictive covariance matrix. Extensive numerical experiments are performed based on a large database of 304 respiratory motion traces to evaluate EKF-GPRN(+) . The experimental results show that the EKF-GPRN(+) algorithm reduces the patient-wise prediction error to 38%, 40% and 40% in root-mean square, compared to no prediction, at lookahead lengths of 192 ms, 384 ms and 576 ms, respectively. The EKF-GPRN(+) algorithm can further reduce the prediction error by employing the gating function, albeit at the cost of reduced duty cycle. The error reduction allows the clinical target volume to planning target volume (CTV-PTV) margin to be reduced, leading to decreased normal-tissue toxicity and possible dose escalation. The CTV-PTV margin is also evaluated to quantify clinical benefits of EKF-GPRN(+) prediction. PMID- 26878654 TI - Atmospheric Mercury Depositional Chronology Reconstructed from Lake Sediments and Ice Core in the Himalayas and Tibetan Plateau. AB - Alpine lake sediments and glacier ice cores retrieved from high mountain regions can provide long-term records of atmospheric deposition of anthropogenic contaminants such as mercury (Hg). In this study, eight lake sediment cores and one glacier ice core were collected from high elevations across the Himalaya Tibet region to investigate the chronology of atmospheric Hg deposition. Consistent with modeling results, the sediment core records showed higher Hg accumulation rates in the southern slopes of the Himalayas than those in the northern slopes in the recent decades (post-World War II). Despite much lower Hg accumulation rates obtained from the glacier ice core, the temporal trend in the Hg accumulation rates matched very well with that observed from the sediment cores. The combination of the lake sediments and glacier ice core allowed us to reconstruct the longest, high-resolution atmospheric Hg deposition chronology in High Asia. The chronology showed that the Hg deposition rate was low between the 1500s and early 1800, rising at the onset of the Industrial Revolution, followed by a dramatic increase after World War II. The increasing trend continues to the present-day in most of the records, reflecting the continuous increase in anthropogenic Hg emissions from South Asia. PMID- 26878655 TI - From marginal to marginalised: The inclusion of men who have sex with men in global and national AIDS programmes and policy. AB - In the last decade, gay men and other men who have sex with men (msm) have come to the fore of global policy debates about AIDS prevention. In stark contrast to programmes and policy during the first two decades of the epidemic, which largely excluded msm outside of the Western countries, the Joint United Nations Programme on HIV/AIDS now identifies gay men and other msm as 'marginalized but not marginal' to the global response. Drawing on archival data and five waves of United Nations Country Progress Reports on HIV/AIDS (2001-2012), this paper examines the productive power of international organisations in the development and diffusion of the msm category, and considers how international organisations have shaped the interpretation of msm in national policies and programmes. These data show that the increasing separation of sexual identity and sexual behaviour at the global level helped to construct notions of risk and disease that were sufficiently broad to accommodate the diverse interests of global policy-makers, activists, and governments. However, as various international and national actors have attempted to develop prevention programmes for msm, the failure of the msm category to map onto lived experience is increasingly apparent. PMID- 26878657 TI - Chimerism interpretation with a highly sensitive quantitative PCR method: 6 months median latency before chimerism drop below 0.1. PMID- 26878656 TI - Efficacy of cisplatin-based immunochemotherapy plus alloSCT in high-risk chronic lymphocytic leukemia: final results of a prospective multicenter phase 2 HOVON study. AB - Allogeneic stem cell transplantation (alloSCT) remains the only curative option for CLL patients. Whereas active disease at the time of alloSCT predicts poor outcome, no standard remission-induction regimen exists. We prospectively assessed outcome after cisplatin-containing immune-chemotherapy (R-DHAP) followed by alloSCT in 46 patients (median age 58 years) fulfilling modified European Society for Blood and Marrow Transplantation (EBMT) CLL Transplant Consensus criteria being refractory to or relapsed (R/R) <1 year after fludarabine or <2 years after fludarabine-based immunochemotherapy or R/R with del(17p). Twenty nine patients received ?3 cycles of R-DHAP and sixteen <3 cycles (4 because of disease progression, 8 for toxicity and 4 toxic deaths). Overall rate of response to R-DHAP was 58%, 31 (67%) proceeded to alloSCT after conditioning with fludarabine and 2 Gy TBI. Twenty (65%) remained free from progression at 2 years after alloSCT, including 17 without minimal residual disease. Intention-to-treat 2-year PFS and overall survival of the 46 patients were 42 and 51% (35.5 months median follow-up); del(17p) or fludarabine refractoriness had no impact. R-DHAP followed by alloSCT is a reasonable treatment to be considered for high-risk CLL patients without access or resistance to targeted therapies. PMID- 26878658 TI - Invariant natural killer T cells in hematopoietic stem cell transplantation: killer choice for natural suppression. AB - Invariant natural killer T cells (iNKTs) are innate-like lipid-reactive T lymphocytes that express an invariant T-cell receptor (TCR). Following engagement of the iTCR, iNKTs rapidly secrete copious amounts of Th1 and Th2 cytokines and promote the functions of several immune cells including NK, T, B and dendritic cells. Accordingly, iNKTs bridge the innate and adaptive immune responses and modulate susceptibility to autoimmunity, infection, allergy and cancer. Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective treatments for patients with hematologic malignancies. However, the beneficial graft versus leukemia (GvL) effect mediated by the conventional T cells contained within the allograft is often hampered by the concurrent occurrence of graft versus host disease (GvHD). Thus, developing strategies that can dissociate GvHD from GvL remain clinically challenging. Several preclinical and clinical studies demonstrate that iNKTs significantly attenuate GvHD without abrogating the GvL effect. Besides preserving the GvL activity of the donor graft, iNKTs themselves exert antitumor immune responses via direct and indirect mechanisms. Herein, we review the various mechanisms by which iNKTs provide antitumor immunity and discuss their roles in GvHD suppression. We also highlight the opportunities and obstacles in manipulating iNKTs for use in the cellular therapy of hematologic malignancies. PMID- 26878660 TI - Sexual function 1-year after allogeneic hematopoietic stem cell transplantation. AB - Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction 1 year after treatment; and (2) associations between sexual dysfunction, body image, anxiety and depression. This controlled prospective cohort study was conducted from October 2010 to November 2013. Patients completed assessments 2-3 weeks before HSCT (N=124) and 1 year after treatment (N=63). Assessment included descriptive data, Sexual Functioning Questionnaire, Body Image Scale and Hospital Anxiety and Depression Scale. The results showed a significant decline in overall sexual function in both men and women (P=<0.001, P=0.010, respectively), although men generally scored higher than women. Forty-seven percent of men and 60% of women reported at least one physical sexual problem 1 year after HSCT. Patients with chronic GVHD trended toward reporting lower levels of sexual function. Finally, women with chronic GVHD scored lower than those without chronic GVHD on the sexual function problem subscale (P=0.008). Sexual dysfunction remains a major problem for men and women 1 year after HSCT and requires routine evaluation and treatment after HSCT. PMID- 26878659 TI - Hematopoietic stem cell transplantation for homozygous beta-thalassemia and beta thalassemia/hemoglobin E patients from haploidentical donors. AB - Thalassemia-free survival after allogeneic stem cell transplantation (SCT) is about 80-90% with either matched-related or -unrelated donors. We explored the use of a mismatched-related ('haplo- ') donor. All patients received two courses of pretransplant immunosuppressive therapy (PTIS) with fludarabine (Flu) and dexamethasone (Dxm). After two courses of PTIS, a conditioning regimen of rabbit antithymocyte globulin, Flu and IV busulfan (Bu) was given followed by T-cell replete peripheral blood progenitor cells. GvHD prophylaxis consisted of cyclophosphamide (Cy) on days SCT +3 and +4 (post-Cy), and on day SCT +5 tacrolimus or sirolimus was started together with a short course of mycophenolate mofetil. Thirty-one patients underwent haplo-SCT. Their median age was 10 years (range, 2-20 years). Twenty-nine patients engrafted with 100% donor chimerism. Two patients suffered primary graft failure. Median time to neutrophil engraftment was 14 days (range, 11-18 days). Five patients developed mild to moderate, reversible veno-occlusive disease, while nine patients developed acute GvHD grade II. Only five patients developed limited-chronic GvHD. Projected overall and event-free survival rates at 2 years are 95% and 94%, respectively. The median follow up time is 12 months (range, 7-33 months). PMID- 26878661 TI - Long-term outcomes of allogeneic hematopoietic cell transplantation with intensified myeloablative conditioning for refractory myeloid malignancy. PMID- 26878664 TI - Authors' correction for Euro Surveill. 2016;21(2). PMID- 26878662 TI - Feasibility of salvage cord blood transplantation following fludarabine, melphalan and low-dose TBI for graft rejection after hematopoietic stem cell transplantation. PMID- 26878663 TI - Digital-PCR assay for screening and quantitative monitoring of calreticulin (CALR) type-2 positive patients with myelofibrosis following allogeneic stem cell transplantation. PMID- 26878665 TI - Synthesis and Characterization of a Walnut Peptides-Zinc Complex and Its Antiproliferative Activity against Human Breast Carcinoma Cells through the Induction of Apoptosis. AB - The walnut peptides and zinc ions were combined to generate a walnut peptides zinc complex (WP1-Zn) with enhanced antiproliferative ability as well as reduced toxicity. The result indicated that Zn ions were successfully combined with WP1 through Zn-N and Zn-O covalent bonds. WP1-Zn compounds exhibited strong antiproliferative ability against the selected human cell lines, especially MCF-7 cells, whose survival rate reduced to 20.02% after exposure to 300 MUg/mL of WP1 Zn for 48 h. WP1-Zn inhibited MCF-7 cell proliferation through inducing cell apoptosis and cell cycle arrest. The results indicated that WP1-Zn induced MCF-7 cell apoptosis via the ROS triggered mitochondrial-mediated pathway and cell surface receptor-mediated pathway. Our work is the first attempt to elucidate the synergic effect of novel walnut peptides and Zn and with the hope of better understanding the antiproliferative action of bioactive peptides and a zinc complex and support the potential application of WP1-Zn as a functional food ingredient or complementary medicine. PMID- 26878666 TI - Pharmacokinetic, pharmacodynamic and clinical evaluation of saxagliptin in type 2 diabetes. AB - INTRODUCTION: Dipeptide peptidase-4 (DPP-4) inhibitors such as saxagliptin are established and efficacious oral therapies in the management of type 2 diabetes. These agents have the potential to confer significant benefits in glycemic control without the risk of weight gain and hypoglycemia, which may be associated with other medications used to treat type 2 diabetes. AREAS COVERED: This review examines the pharmacokinetics, efficacy and tolerability of saxagliptin for the management of type 2 diabetes. EXPERT OPINION: Saxagliptin is routinely used in the management of type 2 diabetes as monotherapy, and in combination with other oral agents and insulin. Robust clinical trials have shown consistent improvements in glycated hemoglobin, fasting and postprandial glucose levels, with few adverse effects. The agent is well tolerated with low rates of hypoglycemia in the absence of insulin or sulphonylurea therapy. PMID- 26878667 TI - 3D scintigraphic imaging and navigation in radioguided surgery: freehand SPECT technology and its clinical applications. AB - Freehand SPECT (fhSPECT) is a technology platform for providing 3-dimensional (3D) navigation for radioguided surgical procedures, such as sentinel lymph node (SLN) biopsy (SLNB). In addition to the information provided by conventional handheld gamma detection probes, fhSPECT allows for direct visualization of the distribution of radioactivity in any given region of interest, allowing for improved navigation to radioactive target lesions and providing accurate lesion depth measurements. Herein, we will review the currently available clinical data on the use of fhSPECT: (i) for SLNB of various malignancies, including difficult to-detect SLNs, and (ii) for radioguided localization of solid tumors. Moreover, the combination of fhSPECT with other technologies (e.g., small field-of-view gamma cameras, and diagnostic ultrasound) is discussed. These technical advances have the potential to greatly expand the clinical application of radioguided surgery in the future. PMID- 26878668 TI - High-Speed Atomic Force Microscopy Revealing Contamination in DNA Purification Systems. AB - Motivated by reports of low-level DNA contamination in popular commercial DNA purification kits, we employed a novel high-speed atomic force microscopy (HS AFM) method to detect and characterize particulate and polymeric contaminants in four such systems: Qiagen MinElute PCR Purification, Zymo Research DNA Clean and Concentrator-5, Invitrogen ChargeSwitch-Pro PCR Purification, and Beckman Coulter AMPure XP. HS-AFM avoids amplification artifacts present in PCR or in the sequencing of amplified products, and it requires no chemical labels and easily achieves near-single-molecule sensitivity. Using this technique, we found trace levels of filamentous contamination, similar in appearance to dsDNA, in eluates from the Zymo, Qiagen, and ChargeSwitch kits. Conversely, we detected no contaminants in magnetic bead-based AMPure XP solutions. Eluates from the Zymo kits also tested positive for DNA in fluorescent intercalator dye and whole genome amplification (WGA) assays. Qiagen kits tested positive in the fluorescence assay but negative in the WGA assay. Both ChargeSwitch and AMPure XP tested negative in the fluorescence assay while the WGA results for these two kits were ambiguous. Taken together, our findings suggest AMPure XP would be the best choice for analyses requiring very high analytical stringency. While HS-AFM alone does not provide chemical specificity, it is a potentially valuable tool for characterizing and quantifying trace contaminants in molecular biology reagents and instruments in cases where conventional techniques fail. PMID- 26878669 TI - Metabolic liver function after stereotactic body radiation therapy for hepatocellular carcinoma. AB - Purpose The time course of changes of the liver function after stereotactic body radiotherapy (SBRT) was analyzed in patients treated for non-resectable hepatocellular carcinoma (HCC). Patients and methods Twenty-six patients with non resectable HCC treated with SBRT were included in this study. Clinical, biochemical and treatment-related parameters were retrospectively collected. S albumin, s-bilirubin, s-alkaline phosphatase (AP) and s-alanine transaminase (ALAT) at 0, 3, 6, and 12 months after radiotherapy were analyzed. Results Seventeen and nine patients were Child-Pugh class A and B, respectively. The liver was exposed to relatively high radiation doses with mean doses of 1.9-26 Gy. None of the patients developed classic radiotherapy-induced liver disease (RILD), but two patients developed non-classic RILD. Two patients developed grade 3 ascites and no grade 4-5 toxicities were observed. Six patients declined in Child-Pugh class. The s-albumin decreased significantly from a pretreatment median of 37.4-34.36 g/l at three months after SBRT and stabilized thereafter. S bilirubin, s-AP and s-ALAT did not change significantly over the study period. Conclusion Despite the fact that patients received high radiation dose to the liver, there was only moderate morbidity related to the treatment. The s-albumin decreases over three months after SBRT reflecting minor to moderate hepatic toxicity. S-albumin should be observed in the follow-up of HCC patients treated with SBRT. PMID- 26878670 TI - Versatile Tandem Ring-Opening/Ring-Closing Metathesis Polymerization: Strategies for Successful Polymerization of Challenging Monomers and Their Mechanistic Studies. AB - Tandem ring-opening/ring-closing metathesis (RO/RCM) results in extremely fast living polymerization; however, according to previous reports, only monomers containing certain combinations of cycloalkenes, terminal alkynes, and nitrogen linkers successfully underwent tandem polymerization. After examining the polymerization pathways, we proposed that the relatively slow intramolecular cyclization might lead to competing side reactions such as intermolecular cross metathesis reactions to form inactive propagating species. Thus, we developed two strategies to enhance tandem polymerization efficiency. First, we modified monomer structures to accelerate tandem RO/RCM cyclization by enhancing the Thorpe-Ingold effect. This strategy increased the polymerization rate and suppressed the chain transfer reaction to achieve controlled polymerization, even for challenging syntheses of dendronized polymers. Alternatively, reducing the reaction concentration facilitated tandem polymerization, suggesting that the slow tandem RO/RCM cyclization step was the main reason for the previous failure. To broaden the monomer scope, we used monomers containing internal alkynes and observed that two different polymer units with different ring sizes were produced as a result of nonselective alpha-addition and beta-addition on the internal alkynes. Thorough experiments with various monomers with internal alkynes suggested that steric and electronic effects of the alkyne substituents influenced alkyne addition selectivity and the polymerization reactivity. Further polymerization kinetics studies revealed that the rate-determining step of monomers containing certain internal alkynes was the six-membered cyclization step via beta-addition, whereas that for other monomers was the conventional intermolecular propagation step, as observed in other chain-growth polymerizations. This conclusion agrees well with all those polymerization results and thus validates our strategies. PMID- 26878671 TI - An excitatory basis for divisive normalization in visual cortex. AB - Neurons in visual cortex are connected not only locally, but also through networks of distal connectivity. These distal networks recruit both excitatory and inhibitory synapses and result in divisive normalization. Normalization is traditionally thought to result from increases in synaptic inhibition. By combining optogenetic stimulation and intracellular recordings in mouse visual cortex, we found that, on the contrary, normalization is a result of a decrease in synaptic excitation. PMID- 26878672 TI - Resilience to chronic stress is mediated by noradrenergic regulation of dopamine neurons. AB - Dopamine (DA) neurons in the ventral tegmental area (VTA) help mediate stress susceptibility and resilience. However, upstream mechanisms controlling these neurons remain unknown. Noradrenergic (NE) neurons in the locus coeruleus, implicated in the pathophysiology of depression, have direct connections within the VTA. Here we demonstrate that NE neurons regulate vulnerability to social defeat through inhibitory control of VTA DA neurons. PMID- 26878673 TI - Hippogate: a break-in from entorhinal cortex. PMID- 26878674 TI - 4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior. AB - Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological and optogenetic manipulations, we found that freezing, a behavioral expression of fear, temporally coincided with the development of sustained, internally generated 4-Hz oscillations in prefrontal-amygdala circuits. 4-Hz oscillations predict freezing onset and offset and synchronize prefrontal-amygdala circuits. Optogenetic induction of prefrontal 4-Hz oscillations coordinates prefrontal-amygdala activity and elicits fear behavior. These results unravel a sustained oscillatory mechanism mediating prefrontal amygdala coupling during fear behavior. PMID- 26878677 TI - Effect of Laughter Yoga on Psychological Well-being and Physiological Measures. AB - CONTEXT: In 2014, laughter yoga (LY) achieved the intermediate level, tier 2, under the Title III-D Evidence-based Disease Prevention and Health Promotion Program through the Administration on Aging (AOA). Further research is needed to qualify LY under the criteria for the highest tier, tier 3, to assure continued funding for LY classes at senior centers. OBJECTIVES: The study intended to demonstrate further the benefits of LY and to qualify LY as tier 3 under Title III-D. DESIGN: Using a quasi-experimental design, the research team conducted a preintervention/postintervention study in 3 phases. SETTING: The study was done in a variety of community centers. Phase 1, a pilot phase, was limited to North Carolina, and phase 2 was conducted in multiple states. Phase 3 was held at the North Carolina Area Agency on Aging's annual Volunteer Appreciation meeting. PARTICIPANTS: Participants in phases 1 (n = 109) and 2 (n = 247) enrolled in LY classes. Classes were advertised by fliers posted in community and in retirement centers. The ability of participants to participate in a class was based solely on their desire to participate, regardless of age, ability, health status, or physical impairment. Phase 3 (n = 23) was a convenience sample only. All phases were voluntary. OUTCOME MEASURE: The pre- and posttests for all 3 phases were Likert-scale surveys, 10 questions on the Psychological Outcomes of Well-being (POWB) survey. Pulse and other physiological measurements were also assessed pre- and postintervention. Analysis included a t test on each of the 10 POWB and physiological measures for all phases. RESULTS: All 10 POWB measures for phases 1 and 2 showed significant improvements between the pre- and postintervention testing (P < .001). Phase 3, the control, showed no significant improvement. CONCLUSIONS: The initial study demonstrated that LY meets the criteria to qualify for tier 3 under the Title III-D Evidence-based Disease Prevention and Health Promotion Program and that a large number of Americans, regardless of age and physical ability, could benefit from LY. PMID- 26878675 TI - Composition differences between organic and conventional meat: a systematic literature review and meta-analysis. AB - Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed. PMID- 26878676 TI - Effects of a Supplement Containing Apoaequorin on Verbal Learning in Older Adults in the Community. AB - CONTEXT: The changes in verbal learning and working memory that often occur with aging may result in reduced social and intellectual interactions. These changes significantly affect an individual's quality of life. As humans age, the body's ability to regulate and maintain calcium levels is diminished. Pharmacological manipulation of the entry of free calcium (Ca2+) has been shown to be effective in increasing some aspects of cognitive function in the aged brain. Apoaequorin has been shown in laboratory studies to regulate levels of intracellular calcium in neuronal cells and to provide protection against ischemic cell death. OBJECTIVE: The study was designed to assess the effects of a supplement of apoaequorin on verbal learning and working memory. DESIGN: The current study, the Madison Memory Study, was a randomized, double-blind, placebo-controlled trial. SETTING: The study occurred in Madison, WI, USA. PARTICIPANTS: Participants were 218 community-dwelling adults, aged 40-91 y, with self-reported memory concerns. INTERVENTION: Participants were randomly assigned to receive either apoaequorin (apoaequorin group) or a matched placebo (control group) for 90 d. OUTCOME MEASURES: The study used quantitative, computerized tools for cognitive assessment the CogState International Shopping List (ISL) and the CogState ISL Delayed Recall (ISL-DR). Scores from computerized cognitive tasks were measured at baseline and at several points during the 90-d study. RESULTS: No significant differences existed between the intervention and control groups in any parameter at baseline. The intervention group (apoaequorin group) showed a statistically significant improvement in verbal learning and recall on the ISL and the ISL-DR, respectively, during the 90-d study. Apoaequorin was tolerated very well in the study. CONCLUSIONS: The results indicated a strong relationship between apoaequorin and improvements on a quantitative measure of cognitive function, specifically verbal learning. The study found that apoaequorin is a well tolerated supplement that improved cognitive function in aging adults. The results suggest potential utility for apoaequorin in addressing the declines in cognitive function associated with aging. PMID- 26878678 TI - Commentary on "Effect of Laughter Yoga on Psychological Well-being and Physiological Measures". PMID- 26878679 TI - Can Joan of Arc Serve as an Enduring Model of Empowerment for Women With a Cancer Diagnosis? AB - CONTEXT: Many research studies have shown that arts-based medicine is a viable and effective medical strategy to help people with cancer improve the quality of their lives. The use of arts-based strategies that employ a figure from history as a source of support to help improve the quality of life has not been documented. OBJECTIVE: The current limited study allowed the author the ability to use the materials in her book, If Joan of Arc Had Cancer: Finding Courage, Faith, and Healing From History's Most Inspirational Woman Warrior, to provide support to women who were cancer survivors and to see if the use of Joan of Arc as a healing guide would be relevant. The primary intention was to find out how the book would be received by women with cancer and also to have the opportunity to determine what was helpful and what was not useful for them. DESIGN: The study was a pilot study. SETTING: The study took place at the Gilda's Club, a national support community for people with cancer and their families, in Fort Lauderdale, FL, USA, one of the satellite programs sponsored by the Wellness Community. PARTICIPANTS: Participants were 10 female survivors of cancer who were members of the Gilda's Club. INTERVENTION: Participants took part in a 6-wk workshop. The workshop included arts-based medicine and meditations, based on a book written by the current author. OUTCOME MEASURES: Participants completed surveys both pre- and postintervention. RESULTS: The program had 10 participants, but only 3 women finished the 6-wk program and completed the postintervention survey. After the workshop, the 3 participants indicated in a survey that they were feeling less anxiety and fear and noted that they felt that they had an improved quality of life and felt more empowered with respect to their psychological frames of mind. In addition, when asked on the survey about the effectiveness of their communications with their physicians (ie, their ability to express and discuss their psychosocial and physical needs combined), they also indicated that they felt that their communications had improved. CONCLUSIONS: The current study, conducted with a small group of women who were cancer survivors, has shown that the use of arts-based medicine can be effective and, most particularly, that the use of Joan of Arc as a model for empowerment can be particularly effective. PMID- 26878681 TI - Should Psychiatrists Resurrect the Body? AB - The current article interrogates the mind-body dualism that characterizes modern psychiatry and contends that the dualism is manifested by the relative neglect by psychiatrists of the body, or soma. The article argues that the state of affairs has several consequences, including psychiatrists' underappreciation of the somatic manifestations of mental disorders and of the therapeutic potential of somatic or body-based therapies. Empirical data attest to the association of a range of mental illnesses with somatic pathologies, as does the fact that a range of somatic therapies, including yoga and t'ai chi, are increasingly being shown to be efficacious in the treatment of a range of mental illnesses. The current article contextualizes contemporary Western psychiatry's relative neglect of the body by drawing on some historical as well as cross-cultural perspectives. Although their overall effect has been minimal, various theoretical perspectives in Western psychiatry, including Jungian thought, psychoanalytical psychosomatics, Reichian and related schools, and the phenomenological tradition, have sought to overcome psychiatry's mind-body dualism. Neither has psychiatry incorporated the values of various non-Western schools of medicine that maintain a far more integrated conceptualization of the relationship between mind and body than is seen in modern Western psychiatry. The field of psychosomatics could potentially influence general psychiatry to reverse its bifurcated mind-body relationship, but that field's increasingly narrow mandate and organizational separation from general psychiatry conspire to militate against the latter's incorporation of psychosomatic medicine's conceptual advances or pragmatic insights in any convincing or enduring manner. PMID- 26878680 TI - Evolution of the Perception of the Relationship Between Doctor and Breast Cancer Patient. AB - The current article discusses the author's study of the evolution of the subjective perception of the relationship between physicians and breast cancer patients during recent decades. The article is based on 18 testimonials, mainly autobiographies dating from 1975-2008, which provide relevant information about the psychological experience of breast cancer care. The pathographies show that many patients nowadays still have an intensely negative perception of their therapeutic interactions with health care professionals, which may have a detrimental effect on their affective states, immunity, and outcomes. PMID- 26878682 TI - Volatile Retention and Morphological Properties of Microencapsulated Tributyrin Varied by Wall Material and Drying Method. AB - Butyric acid is an important short-chain fatty acid for intestinal health and has been shown to improve certain intestinal disease states. A triglyceride containing 3 butyric acid esters, tributyrin (TB) can serve as a source of butyric acid; however, the need to target intestinal delivery and mitigate unpleasant sensory qualities has limited its use in food. Microencapsulation, the entrapment of one or more cores within a matrix, may provide a solution to the aforementioned challenge. This research primarily focused on the influence of (1) wall material: whey and soy protein isolate (WPI and SPI, respectively) and gamma cyclodextrin (GCD), (2) wall additives: inulin of varying chain length, and (3) processing method: spray or oven drying (SD or OD, respectively) on the morphological properties and volatile retention of TB within microcapsules. SPI based microcapsules retained significantly less (P < 0.001) TB compared to WPI based microcapsules as measured by gas chromatography. The inclusion of inulin in the SD WPI-based microcapsules increased (P < 0.001) TB retention over WPI-based microcapsules without inulin. Inulin inclusion into WPI-based microcapsules resulted in a smoother, minimally-dented, circular morphology as compared to noninulin containing WPI-based microcapsules as shown by scanning electron microscopy. GCD and TB OD microcapsules retained more (P < 0.001) TB (94.5% +/- 1.10%) than all other WPI, WPI-inulin, and GCD TB SD microcapsules. When spray dried, the GCD-based microcapsules exhibited (P < 0.001) TB retention than all other microcapsules, indicating the GCD may be unsuitable for spray drying. These findings demonstrate that microencapsulated TB in GCD can lead to minimal TB losses during processing that could be utilized in functional food applications for intestinal health. PMID- 26878683 TI - 17beta-Estradiol inhibits TNF-alpha-induced proliferation and migration of vascular smooth muscle cells via suppression of TRAIL. AB - Atherosclerosis is an inflammatory disease and involves migration of vascular smooth muscle cells (VSMCs). Estrogen inhibits VSMCs migration, while the underlying mechanism remains to be revealed. Recent years, there is emerging evidence showing that TNF-related apoptosis-inducing ligand (TRAIL) increases proliferation and migration of VSMCs. In this study, we investigated the regulatory effect of estrogen on TRAIL expression in VSMCs. TNF-alpha greatly enhanced TRAIL protein expression and stimulated VSMCs proliferation and migration. This effect was partially inhibited by the addition of TRAIL neutralizing antibody, suggesting that TRAIL is important in TNF-alpha-induced migration. 17beta-estradiol (E2) inhibited TRAIL expression under TNF-alpha stimulation in a time- and concentration-dependent manner. This effect was was mimicked by ERalpha agonist 4',4",4'''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT), but not ERbeta agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile (DPN), indicating that ERalpha is involved in this action. TNF-alpha led to nuclear factor kappa B (NF-kappaB) p65 phosphorylation and the inhibitor pyrrolidine dithiocarbama (PDTC) inhibited TRAIL expression, suggesting that NF kappaB signaling is crucial for TARIL production. E2 suppressed p65 phosphorylation in VSMCs and the overexpression of p65 subunit reversed the inhibitory effect of E2 on TRAIL expression and cell proliferation and migration. Taken together, our results indicate that E2 inhibits VSMCs proliferation and migration by downregulation of TRAIL expression via suppression of NF-kappaB pathway. PMID- 26878684 TI - Combinational enhancing effects of formulation and encapsulation on digestive stability and intestinal transport of green tea catechins. AB - The hypothesis was that green tea catechins (GTCs) formulated with vitamin C and xylitol followed by enteric coating with hydroxypropyl methyl cellulose phthalate (HPMCP) or encapsulated into gamma-cyclodextrin (gamma-CD) could enhance intestinal absorption of GTCs. Surface morphology and size obtained by SEM were different. Digestive stability of GTCs encapsulated into gamma-CD or coated with HPMCP was enhanced up to 65.56% or 57.63%, respectively. When GTCs were formulated, the digestive stability was greater than the one not formulated. Formulated GTCs followed by encapsulation into gamma-CD significantly increased intestinal transport. Absorption of GTCs was 2.8%, 9.64%, 11.97%, 8.41% and 14.36% for only GTCs, GTCs encapsulated into gamma-CD, formulated GTCs encapsulated into gamma-CD, GTCs coated with HPMCP and formulated GTCs coated with HPMCP, respectively. This study suggests that GTCs, formulated with vitamin C and xylitol followed by gamma-CD encapsulation or HPMCP enteric coating, provide combinational effect to increase bioavailability of GTCs. PMID- 26878686 TI - Susceptibility to monocular deprivation following immersion in darkness either late into or beyond the critical period. AB - An extended duration of darkness starting near the time of birth preserves immature neuronal characteristics and prolongs the accentuated plasticity observed in young animals. Brief periods of complete darkness have emerged as an effective means of restoring a high capacity for neural plasticity and of promoting recovery from the effects of monocular deprivation (MD). We examined whether 10 days of darkness imposed in adulthood or beyond the peak of the critical period could rejuvenate the ability of MD to reduce the size of neuron somata within deprived layers of the cat dorsal lateral geniculate nucleus (dLGN). For adult cats subjected to 10 days of darkness before 7 days of MD, we observed no alteration in neuron size or neurofilament labeling within the dLGN. At 12 weeks of age, MD that followed immediately after 10 days of darkness produced an enhanced reduction of neuron soma size within deprived dLGN layers. For this age we observed that 10 days of darkness also enhanced the loss of neurofilament protein within deprived dLGN layers. These results indicate that, although 10 days of darkness in adulthood does not enhance the susceptibility to 7 days of MD, darkness imposed near the trailing edge of the critical period can restore a heightened susceptibility to MD more typical of an earlier developmental stage. The loss of neurofilament in juveniles exposed to darkness prior to MD suggests that the enhanced capacity for structural plasticity is partially rooted in the ability of darkness to modulate molecules that inhibit plasticity. J. Comp. Neurol. 524:2643-2653, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26878685 TI - Light-Activated Sealing of Acellular Nerve Allografts following Nerve Gap Injury. AB - Introduction Photochemical tissue bonding (PTB) uses visible light to create sutureless, watertight bonds between two apposed tissue surfaces stained with photoactive dye. In phase 1 of this two-phase study, nerve gaps repaired with bonded isografts were superior to sutured isografts. When autograft demand exceeds supply, acellular nerve allograft (ANA) is an alternative although outcomes are typically inferior. This study assesses the efficacy of PTB when used with ANA. Methods Overall 20 male Lewis rats had 15-mm left sciatic nerve gaps repaired using ANA. ANAs were secured using epineurial suture (group 1) or PTB (group 2). Outcomes were assessed using sciatic function index (SFI), gastrocnemius muscle mass retention, and nerve histomorphometry. Historical controls from phase 1 were used to compare the performance of ANA with isograft. Statistical analysis was performed using analysis of variance and Bonferroni all pairs comparison. Results All ANAs had signs of successful regeneration. Mean values for SFI, muscle mass retention, nerve fiber diameter, axon diameter, and myelin thickness were not significantly different between ANA + suture and ANA + PTB. On comparative analysis, ANA + suture performed significantly worse than isograft + suture from phase 1. However, ANA + PTB was statistically comparable to isograft + suture, the current standard of care. Conclusion Previously reported advantages of PTB versus suture appear to be reduced when applied to ANA. The lack of Schwann cells and neurotrophic factors may be responsible. PTB may improve ANA performance to an extent, where they are equivalent to autograft. This may have important clinical implications when injuries preclude the use of autograft. PMID- 26878687 TI - Adsorption-regeneration by heterogeneous Fenton process using modified carbon and clay materials for removal of indigo blue. AB - Indigo blue dye is mainly used in dyeing of denim clothes and its presence in water bodies could have adverse effects on the aquatic system; for this reason, the objective of this study was to promote the removal of indigo blue dye from aqueous solutions by iron and copper electrochemically modified clay and activated carbon and the saturated materials were regenerated by a Fenton-like process. Montmorillonite clay was modified at pH 2 and 7; activated carbon at pH 2 and pH of the system. The elemental X-ray dispersive spectroscopy analysis showed that the optimum pH for modification of montmorillonite with iron and copper was 7 and for activated carbon was 2. The dye used in this work was characterized by infrared. Unmodified and modified clay samples showed the highest removal efficiencies of the dye (90-100%) in the pH interval from 2 to 10 whereas the removal efficiencies decrease as pH increases for samples modified at pH 2. Unmodified clay and copper-modified activated carbon at pH 2 were the most efficient activated materials for the removal of the dye. The adsorption kinetics data of all materials were best adjusted to the pseudo-second-order model, indicating a chemisorption mechanism and the adsorption isotherms data showed that the materials have a heterogeneous surface. The iron-modified clay could be regenerated by a photo-Fenton-like process through four adsorption-regeneration cycles, with 90% removal efficiency. PMID- 26878688 TI - Patients' perspective on surgical intervention for Dupuytren's disease - experiences, expectations and appraisal of results. AB - PURPOSE: To explore patients' perspectives on surgical intervention for Dupuytren's disease (DD), focusing on patients' appraisal of results, involving previous experiences, expectations and patient characters. METHOD: The participants were 21 men, mean age 66 years, scheduled for DD surgery. Qualitative interviews were conducted 2-4 weeks before surgery and 6-8 months after surgery. The model of the Patient Evaluation Process was used as theoretical framework. Data were analyzed using problem-driven content analysis. RESULTS: Five categories are described: previous experiences, expectations before surgery, appraisal of results, expectations of the future and patient character. Previous experiences influenced participants' expectations, and these were used along with other aspects as references for appraisal of results. Participants' appraisal of results concerned perceived changes in hand function, care process, competency and organization, and could vary in relation to patient character. The appraisal of results influenced participants' expectations of future hand function, health and care. CONCLUSIONS: Patients' appraisal of results involved multidimensional reasoning reflecting on hand function, interaction with staff and organizational matters. Thus, it is not enough to evaluate results after DD surgery only by health outcomes as this provides only a limited perspective. Rather, evaluation of results should also cover process and structure aspects of care. Implications for Rehabilitation To improve health care services, it is important to be aware of the role played by patient's previous experiences, expectations as well as staff and organizational aspects of care. Knowledge about patients' experience and view of the results from surgery and rehabilitation should be established by assessment of care effects on health as well as structure and process aspects of care. Evaluation of structure and process aspects of care can be done by using questions about if the patient felt listened to, received clear information and explanations, was included in decision-making, and their view of waiting time or continuity of care. Improving health care services means not only providing the best treatment method available but also developing individualized care by ensuring good interaction with the patient, providing accurate information, and working to improve the structure of the care process. Before treatment, health care providers should have a dialogue with the patient and consider previous experiences and expectations in order to ensure the patient has balanced expectations of the outcome. PMID- 26878689 TI - Direct observation of a 91 bp LacI-mediated, negatively supercoiled DNA loop by atomic force microscope. AB - Escherichia coli lactose repressor (LacI), a tetrameric protein, is a paradigmatic transcriptional factor that controls the expression of lacZYA in the lac operon. It specifically binds to the O1, O2, and O3 operators of the lac promoter, forms DNA loops, and regulates transcription of the lac operon. In this article, utilizing combined techniques of DNA-nicking assay and AFM imaging, we directly observed a 91 bp LacI-mediated, negatively supercoiled DNA loop mimicking the DNA loop between the O1 and O3 operators in the lac promoter. PMID- 26878691 TI - Tunable nanoporous silicon oxide templates by swift heavy ion tracks technology. AB - Nanoporous silicon oxide templates formed by swift heavy ion tracks technology have been investigated. The influence of the heavy ion characteristics, such as type of ion, energy, stopping power and irradiation fluence on the pore properties of the silicon oxide templates, has been studied. Furthermore, the process of pore formation by chemical etching with hydrofluoric acid has been thoroughly investigated by assessing the effect of etchant concentration and etching time. The outcome of this investigation enables us to have precise control over the resulting geometry of nanopores arrays. As a result, guidelines for the creation of a-SiO2/Si templates with tunable parameters and general recommendations for their further application are presented. PMID- 26878690 TI - Biointerfacial phenomena of amlodipine buccomucosal tablets of HPMC matrix system containing polyacrylate polymer/beta-cyclodextrin: Correlation of swelling and drug delivery performance. AB - OBJECTIVES: This study focuses on the development of amlodipine bilayer buccal tablets of hydroxypropyl methylcellulose (HPMC) matrix system containing polyacrylate polymer (Carbopol((r)))/beta-cyclodextrin as the drug layer and ethylcellulose as the non-swellable backing layer, and their biointerfacial phenomena. METHODS: Tablets were evaluated for swelling, erosion and mucoadhesion using buccal mucosal tissue ex vivo. In vitro drug release and ex vivo drug transport across mucosal tissue were also performed in phosphate buffer (pH 6.8). The relationship of swelling with buccoadhesion and buccal permeation of various bilayer tablet formulations containing HPMC alone and in combination with Carbopol or drug-beta-cyclodextrin complex has been prepared. RESULTS: Overall buccoadhesion of the tablet with combination of HPMC and Carbopol was increased significantly compared with that of HPMC alone. Presence of cyclodextrin did not change bioadhesion force and swelling behavior significantly. Ex vivo permeation was increased with the increase of HPMC proportion in other formulations as observed in in vitro dissolution. CONCLUSION: Drug-cyclodextrin complexes in the tablet improved permeation due to its improved dissolution at the site of biointerface of tablet and buccomucosa. Correlations of ex vivo and in vitro data have been established to predict the buccomucosal permeation from the swelling index or drug release alone. PMID- 26878693 TI - The artful management of older patients with acute myeloid leukemia. AB - Acute myeloid leukemia in older patients has historically had a dismal 10-15% long-term survival rate. Although patient frailty plays a role in this disappointing outcome, the primary driver of poor results remains the resistance of disease to current therapies. The optimal management of this difficult-to treat disease should include a careful consideration of disease, patient and treatment factors. Disease factors include cytogenetic and molecular features and the history of an antecedent hematological disorder. Patient factors include age, performance status, comorbid conditions and individual patient preference. We favor intensive induction in most fit older patients but alternatives such as hypomethylating agents and low-dose cytarabine may be considered in patients with other comorbidities. Enrollment of patients into well designed clinical trials addressing important questions remains of utmost importance in order to advance the understanding and treatment of this disease although the best means of drug development remains a challenging dilemma. PMID- 26878692 TI - Optimal drugs for second-line treatment of patients with small-cell lung cancer. AB - INTRODUCTION: Despite the high response rate to chemotherapy, there have been few advances in the treatment of small-cell lung cancer (SCLC) in the last decades. The state-of-the-art second-line therapy and future research developments in relapsed SCLC are reviewed. AREAS COVERED: There are no optimal drugs for second line treatment of recurrent SCLC but only agents registered for this use. Topotecan remains the standard-of-care for the treatment of second-line platinum sensitive SCLC patients worldwide, while amrubicin is another option, but registered only in Japan. To date, no targeted agents reporting interesting results in second-line SCLC treatment are available. The next-generation DNA sequencing should discover somatic gene alterations and their roles in SCLC to help in selecting patients who could benefit from a targeted agent. Two immunotherapeutics, ipilimumab and nivolumab, have shown promising preliminary results and are being investigated in ongoing trials. EXPERT OPINION: Second-line treatment is not an option for most SCLC patients. Given the evidence up to now, the potentials for immuno-oncology in SCLC are high. The hope is that these expectations are met, and that all drugs being developed will offer new and improved treatment options for SCLC patients. PMID- 26878694 TI - Is charm a primary care physician communication skill? PMID- 26878695 TI - Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for Aspergillus fumigatus virulence. AB - Here, we investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The DeltasakA and the double DeltampkC DeltasakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. Both MpkC::GFP and SakA::GFP translocated to the nucleus upon osmotic stress and cell wall damage, with SakA::GFP showing a quicker response. The phosphorylation state of MpkA was determined post exposure to high concentrations of congo red and Sorbitol. In the wild-type strain, MpkA phosphorylation levels progressively increased in both treatments. In contrast, the DeltasakA mutant had reduced MpkA phosphorylation, and surprisingly, the double DeltampkC DeltasakA had no detectable MpkA phosphorylation. A. fumigatus DeltasakA and DeltampkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the DeltampkC DeltasakA double mutant showed highly attenuated virulence, with approximately 50% mice surviving and a 75% reduction in fungal burden. We propose that both cell wall integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during CW biosynthesis. PMID- 26878696 TI - Crowding and visual acuity measured in adults using paediatric test letters, pictures and symbols. AB - Crowding refers to the degradation of visual acuity for target optotypes with, versus without, surrounding features. Crowding is important clinically, however the effect of target-flanker spacing on acuity for symbols and pictures, compared to letters, has not been investigated. Five adults with corrected-to-normal vision had visual acuity measured for modified single target versions of Kay Pictures, Lea Symbols, HOTV and Cambridge Crowding Cards, tests. Single optotypes were presented in isolation and with surrounding features placed 0-5 stroke widths away. Visual acuity measured with Kay Picture optotypes is 0.13-0.19logMAR better than for other test optotypes and varies significantly across picture. The magnitude of crowding is strongest when the surrounding features abut, or are placed 1 stroke-width away from the target optotype. The slope of the psychometric function is steeper in the region just beyond maximum crowding. Crowding is strongest and the psychometric function steepest, with the Cambridge Crowding Cards arrangement, than when any single optotype is surrounded by a box. Estimates of crowding extent are less variable across test when expressed in units of stroke-width, than optotype-width. Crowding for single target presentations of letters, symbols and pictures used in paediatric visual acuity tests can be maximised and made more sensitive to change in visual acuity, by careful selection of optotype, by surrounding the target with similar flankers, and by using a closer target-flanker separation than half an optotype-width. PMID- 26878697 TI - Cortical processing of global form, motion and biological motion under low light levels. AB - Advances in potential treatments for rod and cone dystrophies have increased the need to understand the contributions of rods and cones to higher-level cortical vision. We measured form, motion and biological motion coherence thresholds and EEG steady-state visual evoked potentials (SSVEP) responses under light conditions ranging from photopic to scotopic. Low light increased thresholds for all three kinds of stimuli; however, global form thresholds were relatively more impaired than those for global motion or biological motion. SSVEP responses to coherent global form and motion were reduced in low light, and motion responses showed a shift in topography from the midline to more lateral locations. Contrast sensitivity measures confirmed that basic visual processing was also affected by low light. However, comparison with contrast sensitivity function (CSF) reductions achieved by optical blur indicated that these were insufficient to explain the pattern of results, although the temporal properties of the rod system may also play a role. Overall, mid-level processing in extra-striate areas is differentially affected by light level, in ways that cannot be explained in terms of low-level spatiotemporal sensitivity. A topographical shift in scotopic motion SSVEP responses may reflect either changes to inhibitory feedback mechanisms between V1 and extra-striate regions or a reduction of input to the visual cortex. These results provide insight into how higher-level cortical vision is normally organised in absence of cone input, and provide a basis for comparison with patients with cone dystrophies, before and after treatments aiming to restore cone function. PMID- 26878698 TI - A New Kind of Spatial Inattention Associated With Chronic Limb Pain? AB - Pathological limb pain patients show decreased attention to some stimuli on the painful limb and increased attention to others, a paradox that has dogged the field for over a decade. We hypothesized that pathological pain involves a spatial inattention confined to bodily representations. Patients showed inattention to the painful side for visual processing of body parts but not letters, tactile processing but not auditory, and body-part bisection tasks but not line bisection tasks. We propose the new term "somatospatial inattention" to describe bodily-specific spatial inattention associated with pathological limb pain. PMID- 26878699 TI - Preventing Osteoporosis. PMID- 26878701 TI - Citric acid encapsulation by a double helical foldamer in competitive solvents. AB - A new double helical aromatic oligoamide capsule able to bind to citric acid in polar and protic solvents was prepared. Aromatic amino acids in the sequence encode both structural (strand curvature and double helix formation) and functional features (recognition pattern) of the assembled capsule. PMID- 26878700 TI - The stereoselectivities of tributyltin hydride-mediated reductions of 5-bromo-D glucuronides to L-iduronides are dependent on the anomeric substituent: syntheses and DFT calculations. AB - One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction. PMID- 26878702 TI - Bifunctional ultraviolet/ultrasound responsive composite TiO2/polyelectrolyte microcapsules. AB - Designing and fabricating multifunctional microcapsules are of considerable interest in both academic and industrial research aspects. This work reports an innovative approach to fabricate composite capsules with high UV and ultrasound responsive functionalities that can be used as external triggers for controlled release, yet with enhanced mechanical strength that can make them survive in a harsh environment. Needle-like TiO2 nanoparticles (NPs) were produced in situ into layer-by-layer (LbL) polyelectrolyte (PE) shells through the hydrolysis of titanium butoxide (TIBO). These rigid TiO2 NPs yielded the formed capsules with excellent mechanical strength, showing a free standing structure. A possible mechanism is proposed for the special morphology formation of the TiO2 NPs and their reinforcing effects. Synergistically, their response to UV and ultrasound was visualized via SEM, with the results showing an irreversible shell rapture upon exposure to either UV or ultrasound irradiation. As expected, the release studies revealed that the dextran release from the TiO2/PE capsules was both UV dependent and ultrasound-dependent. Besides, the biocompatibility of the capsules with the incorporation of amorphous TiO2 NPs was confirmed by an MTT assay experiment. All these pieces of evidence suggested a considerable potential medicinal application of TiO2/PE capsules for controlled drug delivery. PMID- 26878703 TI - No need for external orthogonality in subsystem density-functional theory. AB - Recent reports on the necessity of using externally orthogonal orbitals in subsystem density-functional theory (SDFT) [Annu. Rep. Comput. Chem., 8, 2012, 53; J. Phys. Chem. A, 118, 2014, 9182] are re-investigated. We show that in the basis-set limit, supermolecular Kohn-Sham-DFT (KS-DFT) densities can exactly be represented as a sum of subsystem densities, even if the subsystem orbitals are not externally orthogonal. This is illustrated using both an analytical example and in basis-set free numerical calculations for an atomic test case. We further show that even with finite basis sets, SDFT calculations using accurate reconstructed potentials can closely approach the supermolecular KS-DFT density, and that the deviations between SDFT and KS-DFT decrease as the basis-set limit is approached. Our results demonstrate that formally, there is no need to enforce external orthogonality in SDFT, even though this might be a useful strategy when developing projection-based DFT embedding schemes. PMID- 26878704 TI - Multiple-Armed Tetrahedral DNA Nanostructures for Tumor-Targeting, Dual-Modality in Vivo Imaging. AB - In this work, we have developed multiple-armed DNA tetrahedral nanostructures (TDNs) for dual-modality in vivo imaging using near-infrared (NIR) fluorescence and single-photon emission computed tomography (SPECT). We found that the presence of arm strands in TDNs remarkably enhanced their in vitro stability, allowing them to stay intact for at least 12 h in serum. By using NIR fluorescence imaging, we evaluated in mice the pharmacokinetics of TDNs, which exhibited distinctly different in vivo biodistribution patterns compared with those of double-stranded (ds)DNA. We also noticed that TDNs had twofold longer circulation time in the blood system than that of dsDNA. With the use of multiple armed TDNs, we could precisely anchor an exact number of functional groups including tumor-targeting folic acid (FA), NIR emitter Dylight 755, and radioactive isotope (99m)Tc on prescribed positions of TDNs, which showed the capability of targeted imaging ability in cancer cells. Furthermore, we realized noninvasive tumor-targeting imaging in tumor-bearing mice by using both NIR and SPECT modalities. PMID- 26878705 TI - Synthesis, characterization and Cu(2+) triggered selective fluorescence quenching of Bis-calix[4]arene tetra-triazole macrocycle. AB - A novel fluorescent bis-calix[4]arene macrocycle 9 incorporating metal-binding pockets was successfully prepared. The structure of macrocycle 9 and its precursors were characterized via EI-MS, MALDI-TOF-MS, ESI-MS, (1)H NMR, (13)CNMR, 2D NMR, and X-ray crystallography. The macrocycle 9 displayed selective fluorescence quenching after interacting with Cu(2+) in the presence competing metal cations including Mg(2+), Ca(2+), Ba(2+), Ag(+), Zn(2+), Ti(4+),Cd(2+), Hg(2+), Pb(2+), In(3+), La(3+), Cr(3+), Ni(2+), Sb(3+), V(5+), Fe(3+), Co(2+), Sn(2+), Sn(2+), and Tl(+). The Cu(2+) limit of detection was found to be 40 nM much lower than its threshold level (~ 20 MUM) in drinking water permitted by the U.S Environmental Protection Agency (EPA). Furthermore, drinking water samples from Karachi University (Pakistan) spiked with Cu(2+) were analysed with the sensing system and the results showed an excellent agreement with the fluorescence quenching phenomenon of macrocycle 9 examined in deionized water. Importantly, the chemosensor 9 could be used to detect Cu(2+) in living cells. PMID- 26878706 TI - Preparation of graphene oxide-manganese dioxide for highly efficient adsorption and separation of Th(IV)/U(VI). AB - Manganese dioxide decorated graphene oxide (GOM) was prepared via fixation of crystallographic MnO2 (alpha, gamma) on the surface of graphene oxide (GO) and was explored as an adsorbent material for simultaneous removal of thorium/uranium ions from aqueous solutions. In single component systems (Th(IV) or U(VI)), the alpha-GOM2 (the weight ratio of GO/alpha-MnO2 of 2) exhibited higher maximum adsorption capacities toward both Th(IV) (497.5mg/g) and U(VI) (185.2 mg/g) than those of GO. In the binary component system (Th(IV)/U(VI)), the saturated adsorption capacity of Th(IV) (408.8 mg/g)/U(VI) (66.8 mg/g) on alpha-GOM2 was also higher than those on GO. Based on the analysis of various data, it was proposed that the adsorption process may involve four types of molecular interactions including coordination, electrostatic interaction, cation-pi interaction, and Lewis acid-base interaction between Th(IV)/U(VI) and alpha-GOM2. Finally, the Th(IV)/U(VI) ions on alpha-GOM2 can be separated by a two-stage desorption process with Na2CO3/EDTA. Those results displayed that the alpha-GOM2 may be utilized as an potential adsorbent for removing and separating Th(IV)/U(VI) ions from aqueous solutions. PMID- 26878707 TI - Sequestration of chelated copper by structural Fe(II): Reductive decomplexation and transformation of Cu(II)-EDTA. AB - Chelated coppers, such as Cu(II)-EDTA, are characteristically refractory and difficult to break down because of their high stability and solubility. Cu(II) EDTA sequestration by structural Fe(II) (Fe(II)) was investigated intensively in this study. Up to 101.21mgCu(II)/gFe(II) was obtained by Fe(II) in chelated copper sequestration under near neutral pH condition (pH 7.70). The mechanism of Cu(II)-EDTA sequestration by Fe(II) was concluded as follows: 3Cu(II) EDTA+7Fe(II)+9H2O -> Cu(0)?+ Cu2O?(the major product)+2Fe2O3.H2O?+3Fe(II)-EDTA +14H(+) Novel results strongly indicate that Cu(II) reductive transformation induced by surface Fe(II) was mainly responsible for chelated copper sequestration. Cu(0) generation was initially facilitated, and subsequent reduction of Cu(II) into Cu(I) was closely combined with the gradual increase of ORP (Oxidation-Reduction Potential). Cu-containing products were inherently stable, but Cu2O would be reoxidized to Cu(II) with extra-aeration, resulting in the release of copper, which was beneficial to Cu reclamation. Concentration diminution of Cu(II)-EDTA within the electric double layer and competitive adsorption were responsible for the negative effects of Ca(2+), Mg(2+). By generating vivianite, PO4(3-) was found to decrease surface Fe(II) content. This study is among the first ones to identify the indispensible role of reductive decomplexation in chelated copper sequestration. Given the high feasibility and reactivity, Fe(II) may provide a potential alternative in chelated metals pollution controlling. PMID- 26878708 TI - Differentiation of five body fluids from forensic samples by expression analysis of four microRNAs using quantitative PCR. AB - Applying molecular genetic approaches for the identification of forensically relevant body fluids, which often yield crucial information for the reconstruction of a potential crime, is a current topic of forensic research. Due to their body fluid specific expression patterns and stability against degradation, microRNAs (miRNA) emerged as a promising molecular species, with a range of candidate markers published. The analysis of miRNA via quantitative Real Time PCR, however, should be based on a relevant strategy of normalization of non biological variances to deliver reliable and biologically meaningful results. The herein presented work is the as yet most comprehensive study of forensic body fluid identification via miRNA expression analysis based on a thoroughly validated qPCR procedure and unbiased statistical decision making to identify single source samples. PMID- 26878709 TI - Magnetic resonance energy and topological resonance energy. AB - Ring-current diamagnetism of a polycyclic pi-system is closely associated with thermodynamic stability due to the individual circuits. Magnetic resonance energy (MRE), derived from the ring-current diamagnetic susceptibility, was explored in conjunction with graph-theoretically defined topological resonance energy (TRE). For many aromatic molecules, MRE is highly correlative with TRE with a correlation coefficient of 0.996. For all pi-systems studied, MRE has the same sign as TRE. The only trouble with MRE may be that some antiaromatic and non alternant species exhibit unusually large MRE-to-TRE ratios. This kind of difficulty can in principle be overcome by prior geometry-optimisation or by changing spin multiplicity. Apart from the semi-empirical resonance-theory resonance energy, MRE is considered as the first aromatic stabilisation energy (ASE) defined without referring to any hypothetical polyene reference. PMID- 26878710 TI - Bioavailability, rheology and sensory evaluation of fat-free yogurt enriched with VD3 encapsulated in re-assembled casein micelles. AB - Vitamin D3 (VD3) deficiency is a global problem. Better ways are needed to enrich foods with this important nutraceutical. VD3 is fat-soluble, hence requiring a suitable vehicle for enriching nonfat foods. Our objectives were to assess the bioavailability of VD3, from fat-free yogurt, in re-assembled casein micelles (rCMs) compared to that in polysorbate-80 (PS80/Tween-80) a commonly used synthetic emulsifier, and to assess and compare their rheology and palatability. We enriched fat-free yogurt with VD3 loaded into either rCM (VD3-rCMs) or PS80 (VD3-PS80). In vivo VD3 bioavailability was evaluated by a large randomized, double blind, placebo-controlled clinical trial, measuring serum 25(OH)D increase in subjects who consumed fat-free yogurt with 50,000 IU of either VD3-rCM, VD3 PS80, or VD3-free placebo yogurt. Both VD3-rCM and VD3-PS80 increased the serum 25(OH)D levels by ~8 ng ml(-1) and no significant differences in mean 25(OH)D levels were observed, evidencing the fact that VD3 bioavailability in rCM was as high as that in the synthetic emulsifier. VD3-rCM yogurt had a higher viscosity than VD3-PS80 yogurt. In sensory evaluations, panelists were able to discern between VD3-rCM and VD3-PS80 yogurt, and showed a dislike for PS80 yogurt, compared to rCM or the unenriched control. These results complement our past results showing higher protection against thermal treatment, UV irradiation, and deterioration during shelf life, conferred to hydrophobic nutraceuticals by rCM compared to that by the synthetic surfactant or to the unprotected bioactive, in showing the advantageous use of rCM over the synthetic emulsifier as a delivery system for the enrichment of food with VD3 and other hydrophobic nutraceuticals. PMID- 26878711 TI - Electrophoretic deposition of tannic acid-polypyrrolidone films and composites. AB - Thin films of polyvinylpyrrolidone (PVP)-tannic acid (TA) complexes were prepared by a conceptually new strategy, based on electrophoretic deposition (EPD). Proof of concept investigations involved the analysis of the deposition yield, FTIR and UV-vis spectroscopy of the deposited material, and electron microscopy studies. The analysis of the deposition mechanism indicated that the limitations of the EPD in the deposition of small phenolic molecules, such as TA, and electrically neutral polymers, similar to PVP, containing hydrogen-accepting carbonyl groups, can be avoided. The remarkable adsorption properties of TA and film forming properties of the PVP-TA complexes allowed for the EPD of materials of different types, such as huntite mineral platelets and hydrotalcite clay particles, TiO2 and MnO2 oxide nanoparticles, multiwalled carbon nanotubes, TiN and Pd nanoparticles. Moreover, PVP-TA complexes were used for the co-deposition of different materials and formation of composite films. In another approach, TA was used as a capping agent for the hydrothermal synthesis of ZnO nanorods, which were then deposited by EPD using PVP-TA complexes. The fundamental adsorption and interaction mechanisms of TA involved chelation of metal atoms on particle surfaces with galloyl groups, pi-pi interactions and hydrogen bonding. The films prepared by EPD can be used for various applications, utilizing functional properties of TA, PVP, inorganic and organic materials of different types and their composites. PMID- 26878713 TI - [Autism-friendly dental care]. AB - Autism Spectrum Disorder (ASD) occurs in approximately 1% of the Dutch population. Among the group of patients with this disorder, there is a substantial diversity regarding skills, intelligence and treatability. However, there are also common characteristics; people with ASD often have difficulty with social interaction, communication, and exhibit typical patterns of behaviour. Therefore, problems may arise in the various areas of development, such as language development and responding to sensory stimuli. Dental practitioners will also be confronted with individuals with ASD. Care can be significantly improved, considering that negative experiences and dental anxiety are widespread at this time. PMID- 26878712 TI - Development of monoclonal gammopathy under biotherapy in psoriasis: a French multicenter retrospective study. AB - BACKGROUND: Biotherapies or targeted therapies are fairly new treatments indicated for moderate to severe psoriasis. The side effects appear to be mainly infectious or cancerous. The role of biotherapies in the development of a pre cancerous condition, monoclonal gammopathy of undetermined significance (MGUS), has recently been debated in the literature. OBJECTIVES: To evaluate the incidence of MGUS in psoriasis patients treated with biotherapy. MATERIALS AND METHODS: This study was a French multicenter retrospective study carried out through the French multicenter study group RESOPSO. Data on the results of serum protein electrophoreses performed before and within at least six months after the start of the biotherapy were collected. Demographic data, medical history, and psoriasis treatment history were specified. RESULTS: Four hundred and forty three patients were eligible for inclusion. Of these, three presented with monoclonal gammopathy for which the assessment was in favor of MGUS. The average treatment period was 19.7 months. Six patients presented with MGUS prior to the treatment. These patients' immunoglobulin levels remained stable, with an average remission of 24 months. Only psoriatic rheumatism appeared to be statistically linked to MGUS. CONCLUSION: The incidence and frequency of MGUS in psoriasis patients treated with biotherapy do not appear to increase relative to the general population. PMID- 26878714 TI - [Implant positioned buccally of the alveolar process; a complication]. AB - Because of a blue discolouration of her mucosa a 58-year-old patient visited her new dentist. Her medical history revealed that several months before an implant in the region of dental element 22 had been installed. When palpating the alveolar region, a painless hard swelling was felt. As a malposition of the implant was suspected, it was decided to have a cone beam computed tomography scan made. The sagittal scan revealed that apically the implant in the region of dental element 22 was not embedded in the jawbone. Following the placement of an implant, it is always necessary to verify that the implant procedure has been carried out successfully; palpating the implant bed is always required. PMID- 26878715 TI - [Endodontic re-treatment or apical surgery, is an evidence-based choice possible?]. AB - Treatment of a recurrence after an initial endodontic treatment can consist of endodontic re-treatment or apical surgery. The literature reports comparable success rates for these two options. However, randomised controlled trials that are truly comparable to each other are unavailable as a result of which comparison and an informed choice are not really possible. In addition to the treatment outcome, consideration also has to be given to cost-effectiveness and other patient-related factors, such as pain, swelling and medication. Regarding these considerations, too, little reliable information can be found in the literature. Moreover, factors relating to insurance play an important role in the Netherlands, where only apical surgery is covered by the basic healthcare insurance. In conclusion, all of these factors should be carefully considered before proceeding to an individual treatment strategy. PMID- 26878716 TI - [Dissertations 25 years after date 44. Behaviour at high temperatures of palladium based dental alloys]. AB - In the Netherlands in the 1980s palladium based dental alloys were often used in substructures of metal-ceramic restorations. However, after their introduction to the market some unexplained problems came to light: porosity on the metal-ceramic interface, frequent failure of solder joints, margin lift and distortion of bigger constructions. Later, palladium allergies could be added to the list. A 1989 dissertation investigated these problems and underlying causes and came up with answers and solutions. Recent problems like the breakage and chipping of porcelain on zirconia cores shows again that industry is sometimes unaware of adjustment problems at the moment that a new product is introduced to the market. PMID- 26878717 TI - [Left- or right-handed: the effect of a preferential use of one hand or the other on dental hygiene]. AB - A research project investigated the extent to which a preferential use of one hand or the other has an effect on dental hygiene on the left or right side of the mouth. The study made use of epidemiological dental-care data from the Netherlands Organisation for Applied Scientific Research and of data from a dental practice specifically collected for this project. The results revealed that among a population which is 85-90% right-handed, statistically significantly more dental plaque was found on the right side of the mouth than on the left. A separate study revealed the prevalence of statistically significantly more dental plaque on the right side than on the left among right-handed people and, among left-handed people, a non-statistically significant trend of more dental plaque on the left than the right. It is concluded that dental hygiene on the left side and the right side of the mouth is very likely to be dependent on the preferential use of one hand or the other. The differences between the left side of the mouth and right among left- and right-handed people are, however, so small that it is questionable whether these should be taken into consideration in giving instructions about dental hygiene. PMID- 26878718 TI - Alpha and gamma band oscillations index differential processing of acoustically reduced and full forms. AB - Reduced forms like yeshay for yesterday often occur in conversations. Previous behavioral research reported a processing advantage for full over reduced forms. The present study investigated whether this processing advantage is reflected in a modulation of alpha (8-12Hz) and gamma (30+Hz) band activity. In three electrophysiological experiments, participants listened to full and reduced forms in isolation (Experiment 1), sentence-final position (Experiment 2), or mid sentence position (Experiment 3). Alpha power was larger in response to reduced forms than to full forms, but only in Experiments 1 and 2. We interpret these increases in alpha power as reflections of higher auditory cognitive load. In all experiments, gamma power only increased in response to full forms, which we interpret as showing that lexical activation spreads more quickly through the semantic network for full than for reduced forms. These results confirm a processing advantage for full forms, especially in non-medial sentence position. PMID- 26878719 TI - Spatio-temporal gait disorder and gait fatigue index in a six-minute walk test in women with fibromyalgia. AB - BACKGROUND: Gait disorders in fibromyalgia patients affect several gait parameters and different muscle recruitment patterns. The aim of this study was to assess the gait differences observed during a six-minute walk test between fibromyalgia patients and healthy controls. METHODS: Forty-eight women with fibromyalgia and 15 healthy women were evaluated. Fibromyalgia patients met the American College of Rheumatology criteria for fibromyalgia selected of an ambulatory care. Both patients and controls had a negative history of musculoskeletal disease, neurological disorders, and gait abnormalities. The 15 controls were healthy women matched to the patients in age, height and body weight. Spatio-temporal gait variables and the rate of perceived exertion during the six-minute walk test (all subjects) and Fibromyalgia Impact Questionnaire (fibromyalgia subjects) were evaluated. All walking sets on the GaitRITE were collected and the gait variables were selected at three stages during the six minute walk test: two sets at the beginning, two sets at 3 min and two sets at the end of the test. In addition, the Fibromyalgia Impact Questionnaire was used for the fibromyalgia patients. FINDINGS: Fibromyalgia patients showed a significant decrease in all spatio-temporal gait variables at each of the three stages and had a lower walk distance covered in the six-minute walk test and higher rate of perceived exertion. No correlations were found between the Fibromyalgia Impact Questionnaire and gait variables. The fibromyalgia and control subjects showed lower gait fatigue indices between the middle and last stages. INTERPRETATION: Gait analysis during a six-minute walk test is a good tool to assess the fatigue and physical symptoms of patients with fibromyalgia. PMID- 26878720 TI - In vivo tracing of organophosphorus pesticides in cabbage (Brassica parachinensis) and aloe (Barbadensis). AB - In vivo solid-phase microextraction (SPME) sampling method coupled with gas chromatography-mass spectrometry (GC-MS) analysis was employed to trace the uptake and elimination of organophosphorus pesticides (OPPs) in two kinds of edible plants, cabbage (Brassica parachinensis) and aloe (Barbadensis). The metabolism of fenthion in aloe was also investigated by the liquid chromatography tandem mass spectrometry analysis (LC-MS/MS) to understand the fate of OPPs in living plants better. Transpiration stream concentration factor (TSCF) and depuration rate constants of the OPPs in living plants were obtained therein. The health risk of the OPPs treated aloe was estimated by the maximum residue limit (MRL) approach, and it revealed that the OPPs were rather safe for their fast degradable property. However, peak concentration of fenthion-sulfoxide was found to exceed the MRL and was higher than that of the parent fenthion, which indicated the potential risk of pesticide metabolites. This study highlighted the application of in vivo SPME for contaminant tracing in different living edible plants. The in vivo tracing method is very convenient and can provide more data to evaluate the risk of different pesticides, which are very important for the safety of agriculture production. PMID- 26878721 TI - Finite-time robust stabilization of uncertain delayed neural networks with discontinuous activations via delayed feedback control. AB - This paper is concerned with the finite-time robust stabilization of delayed neural networks (DNNs) in the presence of discontinuous activations and parameter uncertainties. By using the nonsmooth analysis and control theory, a delayed controller is designed to realize the finite-time robust stabilization of DNNs with discontinuous activations and parameter uncertainties, and the upper bound of the settling time functional for stabilization is estimated. Finally, two examples are provided to demonstrate the effectiveness of the theoretical results. PMID- 26878722 TI - Quantum perceptron over a field and neural network architecture selection in a quantum computer. AB - In this work, we propose a quantum neural network named quantum perceptron over a field (QPF). Quantum computers are not yet a reality and the models and algorithms proposed in this work cannot be simulated in actual (or classical) computers. QPF is a direct generalization of a classical perceptron and solves some drawbacks found in previous models of quantum perceptrons. We also present a learning algorithm named Superposition based Architecture Learning algorithm (SAL) that optimizes the neural network weights and architectures. SAL searches for the best architecture in a finite set of neural network architectures with linear time over the number of patterns in the training set. SAL is the first learning algorithm to determine neural network architectures in polynomial time. This speedup is obtained by the use of quantum parallelism and a non-linear quantum operator. PMID- 26878723 TI - An expanded sequence context model broadly explains variability in polymorphism levels across the human genome. AB - The rate of single-nucleotide polymorphism varies substantially across the human genome and fundamentally influences evolution and incidence of genetic disease. Previous studies have only considered the immediately flanking nucleotides around a polymorphic site--the site's trinucleotide sequence context--to study polymorphism levels across the genome. Moreover, the impact of larger sequence contexts has not been fully clarified, even though context substantially influences rates of polymorphism. Using a new statistical framework and data from the 1000 Genomes Project, we demonstrate that a heptanucleotide context explains >81% of variability in substitution probabilities, highlighting new mutation promoting motifs at ApT dinucleotide, CAAT and TACG sequences. Our approach also identifies previously undocumented variability in C-to-T substitutions at CpG sites, which is not immediately explained by differential methylation intensity. Using our model, we present informative substitution intolerance scores for genes and a new intolerance score for amino acids, and we demonstrate clinical use of the model in neuropsychiatric diseases. PMID- 26878726 TI - [Management of Glaucoma Patients]. PMID- 26878727 TI - [Communication Strategies in Dealing with Patients with Glaucoma]. AB - When patients with glaucoma meet doctors and their assistants in a doctor's office or a hospital all hope that this contact will be trouble-free, helpful, perhaps even happy and conducted in a constructive spirit. But this is not always the case. Words and gestures may accidently hurt or reject the patient. Often the communication results in harm instead of help and healing. For this reason, it is worthwhile to have a glimpse behind the curtain of the difficult interactions between people. The rules of communication in the medical context will help to facilitate the contact between doctors and patients. Verbal and non-verbal communication play an important role, for example in how to address the individual patient, as well as the timing and wording. Expertise in communication is a key qualification for medical professionals! PMID- 26878724 TI - NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. AB - Widely used as anticancer and immunosuppressive agents, thiopurines have narrow therapeutic indices owing to frequent toxicities, partly explained by TPMT genetic polymorphisms. Recent studies identified germline NUDT15 variation as another critical determinant of thiopurine intolerance, but the underlying molecular mechanisms and the clinical implications of this pharmacogenetic association remain unknown. In 270 children enrolled in clinical trials for acute lymphoblastic leukemia in Guatemala, Singapore and Japan, we identified four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile and p.Val18_Val19insGlyVal) that resulted in 74.4-100% loss of nucleotide diphosphatase activity. Loss-of-function NUDT15 diplotypes were consistently associated with thiopurine intolerance across the three cohorts (P = 0.021, 2.1 * 10(-5) and 0.0054, respectively; meta-analysis P = 4.45 * 10(-8), allelic effect size = -11.5). Mechanistically, NUDT15 inactivated thiopurine metabolites and decreased thiopurine cytotoxicity in vitro, and patients with defective NUDT15 alleles showed excessive levels of thiopurine active metabolites and toxicity. Taken together, these results indicate that a comprehensive pharmacogenetic model integrating NUDT15 variants may inform personalized thiopurine therapy. PMID- 26878728 TI - [Complexities of Medical Glaucoma Therapy--the Elderly Patient in Focus]. AB - In order to treat glaucoma with medication successfully, the patient needs to participate actively in the process. "Adherence", formerly "compliance", describes the willingness and capacity to follow the prescribed regimen every day. It is not trivial to measure adherence and persistence, as this quite often relies on self reports by the patient or speculations by the physician. Hence, the overall reported adherence may vary from 5 to 95 %. In general, the following categories have been defined for reduced adherence: medication-related factors, patient-related factors, environmental factors and social factors. Age has been found to intensify or modify many of these factors. Older adults often face various challenges, due to motor disabilities, reduced visual acuity or impaired cognitive capabilities. In patients with movement disorders or tactile limitations, the target area can be reached more successfully with standard eye drop bottles than with single-use dose units. This should be considered if antiglaucoma eye drops are prescribed in the elderly. Frequency of application is a main factor influencing adherence. Monotherapy--as provided with prostaglandins -or drops with a fixed combination have proven to support adherence significantly. A significant boost for self-monitoring activities is initiated by the growing market of electronic devices, like smartphones. For instance, they can provide acoustic alarms as reminders to apply the eye drops. It is evident that any external support or disease-related information by family members, the medical practitioners, support groups or even electronic devices may improve adherence and persistence, even in patients with severe impairments. PMID- 26878725 TI - Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome. AB - Nucleoporins are essential components of the nuclear pore complex (NPC). Only a few diseases have been attributed to NPC dysfunction. Steroid-resistant nephrotic syndrome (SRNS), a frequent cause of chronic kidney disease, is caused by dysfunction of glomerular podocytes. Here we identify in eight families with SRNS mutations in NUP93, its interaction partner NUP205 or XPO5 (encoding exportin 5) as hitherto unrecognized monogenic causes of SRNS. NUP93 mutations caused disrupted NPC assembly. NUP93 knockdown reduced the presence of NUP205 in the NPC, and, reciprocally, a NUP205 alteration abrogated NUP93 interaction. We demonstrate that NUP93 and exportin 5 interact with the signaling protein SMAD4 and that NUP93 mutations abrogated interaction with SMAD4. Notably, NUP93 mutations interfered with BMP7-induced SMAD transcriptional reporter activity. We hereby demonstrate that mutations of NUP genes cause a distinct renal disease and identify aberrant SMAD signaling as a new disease mechanism of SRNS, opening a potential new avenue for treatment. PMID- 26878729 TI - [Aids for Patients with Glaucoma and Visual Impairment]. AB - This article provides a broad overview of the existing medical aids and appliances for patients suffering from glaucoma and/or visual impairment. Furthermore, instructions for proper handling of eye drop therapy are given. There are many different public services to support patients with visual impairment and that aim to restore their mobility and autonomy in daily life. About 20,000 medical aids and tools are currently listed as refundable by insurances. The available supply ranges from magnifying reading aids to electronic aids and appliances to train patients' orientation, mobility and skills of every day life. Qualified professionals may be employed by organisations such as the DBSV e. V. and can accompany, support and counsel patients and their families with their specialised knowledge. PMID- 26878730 TI - [Quality of Life in Patients with Glaucoma]. AB - BACKGROUND: The goal of glaucoma treatment is to maintain the patient's visual function and related quality of life, at a sustainable cost. In this review, methods of measuring quality of life are presented, together with their impact in clinical practice. METHODS: Searches were from the inception of the database to date. Electronic databases searched included Medline (Ovid), Medline In-Process (Ovid), and Embase (Ovid). In a semistructured approach, the articles were checked for their eligibility to provide information about the measurement and application of quality of life in glaucoma patients. RESULTS: Well established questionnaires are available to measure quality of life in glaucoma patients, as well as instruments to measure benefits. Performance-based measures are more time consuming. The Glaucoma Activity Limitation-9 Questionnaire (GAL-9) is a glaucoma specific questionnaire in German, with a Rasch analysis. In eye diseases with central visual field defects, it is the better eye that determines the patient's quality of life, whereas in glaucoma patients with peripheral defects, it is the worse eye that has a stronger influence. Structural changes in glaucoma are less well correlated with quality of life than are functional impairments. There have been a few initial reports of patterns of visual field defects that correlate with subjective impairments. CONCLUSIONS: The data can help to improve our understanding of individual patient impairment and support our efforts to improve the medical advice and therapy that these patients receive. PMID- 26878731 TI - [Traffic Aspects in Glaucoma Patients]. AB - Glaucomatous damage may lead to morphological and functional deficits. If these deficits affect both eyes, binocular visual field defects may result. If these field defects are in the areas which are most important for the car driver (centre and horizontal meridian) then the driver may no longer be able to participate actively in road traffic. Mesopic vision and sensitivity to glare may also be affected by glaucomatous damage. The most important point is that the patient is alert to problems in this area and he must be directed to possible ways of compensation, especially for mesopic vision and sensitivity to glare. Binocular visual field defects in the relevant areas, however, cannot be compensated for. PMID- 26878732 TI - [Social Law Entitlements and Compensations for Visually Impaired Patients in Germany, Focussed on Glaucoma]. AB - Although prevention of progression is the most important issue in the treatment of glaucoma patients, information on visual aids and social law entitlements is also helpful. In this article, the main aspects of compensation for visual impairment are outlined so that you can competently support your patients, without much effort, with helpful tips and appropriate instructions. PMID- 26878733 TI - [Intraocular Lens as a Drug Delivery Device: State of the Art and Future Perspective]. AB - Development of an intraocular lens (IOL) as a drug delivery device has been pursued for many years and is a promising concept in modern cataract surgery. Common postoperative conditions such as posterior capsule opacification (PCO), intraocular inflammation or the rare but severe complications of cataract surgery like endophthalmitis are potential therapeutic targets for a drug-eluting IOL. There are three techniques of pharmacological IOL modification: Firstly, surface modification of the IOL ("coating"); secondly, IOL optic modification ("soaking") and lastly, loading the IOL haptics with a slow release system. The last option does not interfere with the IOL optics at all. Therefore, a broad spectrum of pharmacological agents needs to be assessed in preclinical and clinical studies to determine which agent/IOL combination is safe and efficient. For pharmacological PCO prophylaxis, erufosine-loaded IOLs are of great clinical interest. Heparin-coated IOLs might become clinically relevant for attenuation of intraocular inflammation after cataract surgery and cefuroxime-loaded IOLs for endophthalmitis prophylaxis. PMID- 26878734 TI - [On the Interaction between Loss of Earnings, Disability and Inability to Work]. AB - Loss of earnings, disability and inability to work may be used to assess the same health damage, but these legal terms are defined differently, as they have different objectives. Important practical distinctions between these terms are explained and their inter-relationships are discussed. PMID- 26878735 TI - [Not Available]. PMID- 26878736 TI - [Adverse Drug Reactions in Ophthalmology--Update 2015/2016]. PMID- 26878737 TI - Pharmacogenetics and oral antithrombotic drugs. AB - Warfarin and other oral vitamin K antagonists (VKAs) have been the primary pharmacologic options with well-established efficacy data in high-risk patient populations. Warfarin dose requirements to achieve therapeutic anticoagulation are highly variable. This variability in response results in increased risk for adverse events, including thromboembolism and bleeding. Genetic variants in CYP2C9 and VKORC1 have been identified and shown to explain some of the variability in warfarin response. Prospective trials suggest that incorporation of genotype results in faster time to therapeutic range than without; however, whether these improvements result in improved clinical outcomes is unclear. The target-specific anticoagulants are alternatives to warfarin and do not require laboratory monitoring. Some pharmacogenetic variation in their clinical response may exist as well. Ongoing trials will provide a clearer picture of whether genotype-based warfarin dosing improves outcomes and may, therefore, subsequently be compared with the target-specific agents. PMID- 26878738 TI - Removal of Review and Reclassification Procedures for Biological Products Licensed Prior to July 1, 1972. Final rule. AB - The Food and Drug Administration (FDA, the Agency, or we) is removing two regulations that prescribe procedures for FDA's review and classification of biological products licensed before July 1, 1972. FDA is taking this action because the two regulations are obsolete and no longer necessary in light of other statutory and regulatory authorities established since 1972, which allow FDA to evaluate and monitor the safety and effectiveness of all biological products. In addition, other statutory and regulatory authorities authorize FDA to revoke a license for biological products because they are not safe and effective, or are misbranded. FDA is taking this action as part of its retrospective review of its regulations to promote improvement and innovation. PMID- 26878739 TI - Anesthesiology Devices; Reclassification of Membrane Lung for Long-Term Pulmonary Support; Redesignation as Extracorporeal Circuit and Accessories for Long-Term Respiratory/Cardiopulmonary Failure. Final order. AB - The Food and Drug Administration (FDA) is issuing a final order to redesignate membrane lung devices for long-term pulmonary support, a preamendments class III device, as extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure, and to reclassify the device to class II (special controls) in patients with acute respiratory failure or acute cardiopulmonary failure where other available treatment options have failed, and continued clinical deterioration is expected or the risk of death is imminent. A membrane lung device for long-term pulmonary support (>6 hours) refers to the oxygenator in an extracorporeal circuit used during long-term procedures, commonly referred to as extracorporeal membrane oxygenation (ECMO). Because a number of other devices and accessories are used with the oxygenator in the circuit, the title and identification of the regulation are revised to include extracorporeal circuit and accessories for long-term respiratory/cardiopulmonary failure. Although an individual device or accessory used in an ECMO circuit may already have its own classification regulation when the device or accessory is intended for short-term use (<=6 hours), such device or accessory will be subject to the same regulatory controls applied to the oxygenator (i.e., class II, special controls) when evaluated as part of the ECMO circuit for long-term use (>6 hours). On its own initiative, based on new information, FDA is revising the classification of the membrane lung device for long-term pulmonary support. PMID- 26878740 TI - Medical Devices; General and Plastic Surgery Devices; Classification of the Scalp Cooling System To Reduce the Likelihood of Chemotherapy-Induced Alopecia. Final order. AB - The Food and Drug Administration (FDA) is classifying the scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the scalp cooling system to reduce the likelihood of chemotherapy-induced alopecia's classification. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. PMID- 26878741 TI - Medicare Program; Reporting and Returning of Overpayments. Final rule. AB - This final rule requires providers and suppliers receiving funds under the Medicare program to report and return overpayments by the later of the date that is 60 days after the date on which the overpayment was identified; or the date any corresponding cost report is due, if applicable. The requirements in this rule are meant to ensure compliance with applicable statutes, promote the furnishing of high quality care, and to protect the Medicare Trust Funds against fraud and improper payments. This rule provides needed clarity and consistency in the reporting and returning of self-identified overpayments. PMID- 26878742 TI - I CAN'T SLEEP. Americans everywhere are desperate for shut-eye, turning to drugs, supplements, and high-tech gadgets. Here's what works, what doesn't, and what's dangerous. PMID- 26878743 TI - Peeling Back the 'Natural' Label. Companies can slap that magic word on processed food packages even if what's inside contains artificial ingredients. If you find that outrageous, now's the time to join us in letting the FDA know how you feel. PMID- 26878744 TI - Should I try homeopathic cold and flu remedies? PMID- 26878745 TI - STEP RIGHT UP. Body-fat scales come with a ton of high-tech claims. We put them through their paces. PMID- 26878746 TI - Stress associated changes in Pavlovian-instrumental transfer in humans. AB - Predictive learning is known to influence instrumental responding for reward. Cues associated with an instrumental outcome can influence performance in two ways: (a) by selectively promoting actions associated with the outcome predicted by the cue (specific transfer), and (b) by increasing motivation and the vigour of instrumental responding (general transfer). To examine these two distinct processes in humans we developed a novel behavioural task in which participants were able to liberate junk-food snacks from a virtual vending machine. Additionally, the relationship between stress and cue-driven reward seeking was examined using participant scores on the Depression Anxiety and Stress Scale (DASS). Reward-paired cues were found to separately bias action selection and influence the rate of responding for rewards. Furthermore, the effects of reward paired cues on the rate of responding for reward was influenced by increased stress and anxiety. Increased levels of stress and anxiety were associated particularly with changes in cue-driven response vigour; whereas high levels of stress and anxiety were associated with elevated responding above baseline in the presence of a cue associated with a non-rewarding outcome, participants with low levels of anxiety and stress showed appropriate suppression of responding during this cue. These differences in performance between high and low anxiety and stress participants provides initial evidence that, as has been demonstrated in rodents, stress affects the influence of cue-driven response vigour in humans. PMID- 26878747 TI - Differentiation of human endometrial stem cells into endothelial-like cells on gelatin/chitosan/bioglass nanofibrous scaffolds. AB - The capacity of gelatin/chitosan/bioactive glass nanopowders (GEL/CS/BGNPs) scaffolds was investigated for increasing human endometrial stem cells (hEnSCs) differentiation into the endothelial cells in the presence of angiogenic factors. GEL/CS nanofibrous scaffold with different contents of BGNPs were fabricated and assessed. Expression of endothelial markers (CD31, vascular endothelial cadherin (VE-cadherin), and KDR) in differentiated cells was evaluated. Results showed the diameter of nanofiber increases with decreasing the BG content in GEL/CS scaffolds. Moreover, in vitro study indicated that the GEL/CS/BGNPs scaffold with 1.5% BGNPs content provided a suitable three-dimensional structure for endothelial cells differentiation. Thus, the GEL/CS/BGNPs scaffold can be recommended for blood vessels repair. PMID- 26878748 TI - 1.2% Rosuvastatin Versus 1.2% Atorvastatin Gel Local Drug Delivery and Redelivery in Treatment of Intrabony Defects in Chronic Periodontitis: A Randomized Placebo Controlled Clinical Trial. AB - BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are an important group of hypolipidemic drugs that are able to modulate inflammation and alveolar bone loss. Rosuvastatin (RSV) and atorvastatin (ATV) are known to inhibit osteoclastic bone resorption and have been proposed to have osteostimulative properties. The aim of this study is to evaluate and compare the efficacy of 1.2% RSV and 1.2% ATV gel local drug delivery (LDD) and redelivery systems, in addition to scaling and root planing (SRP), for the treatment of intrabony defects (IBDs) in patients with chronic periodontitis (CP). METHODS: A total of 90 individuals with 90 IBDs was randomly allocated to treatment with SRP followed by LDD of 1.2% RSV, 1.2% ATV, or placebo gel. Clinical and radiographic parameters, including plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), clinical attachment level (CAL), and IBD depth, were recorded at baseline and 6 and 9 months. RESULTS: All three groups showed significant reduction in PI and mSBI at all intervals. Mean mSBI and PD reductions, CAL gain, and IBD depth reduction with statin drugs were significantly greater than with placebo gel LDD. Improvements in these parameters were significantly greater with RSV LDD than ATV or placebo gels at 6 and 9 months. CONCLUSION: LDD of 1.2% RSV results in significantly greater clinico-radiographic improvement than 1.2% ATV or placebo gels as adjunct to mechanical periodontal therapy. PMID- 26878749 TI - Long-Term Outcomes of Untreated Buccal Gingival Recessions: A Systematic Review and Meta-Analysis. AB - BACKGROUND: This review aims to: 1) assess the long-term outcomes of untreated buccal gingival recession (GR) defects and the associated reported esthetic and functional alterations; and 2) evaluate which factors influence the progression/worsening of dental and periodontal tissue conditions of untreated GR defects. METHODS: Interventional and observational studies with duration of >=24 months reporting outcomes from adult patients with localized or multiple GR defects not treated by root coverage or gingival augmentation procedures were considered eligible for inclusion. MEDLINE and EMBASE databases were searched for articles published through July 2015. Random-effects meta-analyses were performed comparing baseline versus most recent follow-up outcomes (i.e., number of patients with >=1 GR and number of sites with GR). RESULTS: Of 378 potentially eligible articles, eight (reporting six studies) met inclusion criteria. Of 1,647 GR defects with baseline and follow-up information, 78.1% experienced GR depth increase during the follow-up period, whereas the remaining experienced decrease or no change. Moreover, there was a 79.3% increase in the number of GR defects among the patients followed (i.e., new GR defects). Pooled estimates (data from four studies) showed significantly increased odds of recession development long term, regarding either number of patients (odds ratio 2.43; P = 0.03) or number of sites with GR (odds ratio 2.16; P = 0.0005). CONCLUSION: Untreated recession defects in individuals with good oral hygiene have a high probability of progressing during long-term follow-up. PMID- 26878750 TI - Neural Mechanisms Underlying Anxiety-Chronic Pain Interactions. AB - Chronic pain is a major medical problem that is resistant to conventional medical intervention. It also causes emotional changes such as anxiety and fear. Furthermore, anxiety or fear often enhances the suffering of pain. Based on recent studies, I propose chronic anxiety triggered by injury or chronic pain is mediated through presynaptic long-term potentiation (LTP) in the anterior cingulate cortex (ACC), a key cortical region for pain perception. Conversely, NMDA receptor-dependent postsynaptic LTP plays a more important role in behavioral sensitization in chronic pain. Thus, postsynaptic and presynaptic LTP in ACC neurons are likely the key cellular mechanisms for causing chronic pain and its associated anxiety, respectively. This suggests potential targets for treating chronic pain and related anxiety. PMID- 26878752 TI - Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection. AB - Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability of echovirus 7 (Tulloch et al., 2014). Here, we show that that influenza A virus (IAV) with maximised frequencies of these dinucleotides in segment 5 showed comparable attenuation in cell culture compared to unmodified virus and a permuted control (CDLR). Attenuation was also manifested in vivo, with 10-100 fold reduced viral loads in lungs of mice infected with 200PFU of CpG-high and UpA-high mutants. However, both induced powerful inflammatory cytokine and adaptive (T cell and neutralising antibody) responses disproportionate to their replication. CpG-high infected mice also showed markedly reduced clinical severity, minimal weight loss and reduced immmunopathology in lung, yet sterilising immunity to lethal dose WT challenge was achieved after low dose (20PFU) pre-immunisation with this mutant. Increasing CpG dinucleotide frequencies represents a generic and potentially highly effective method for generating safe, highly immunoreactive vaccines. PMID- 26878755 TI - Non-heat-treated frozen raspberries the most likely vehicle of a norovirus outbreak in Oslo, Norway, November 2013. AB - In November 2013, the Norwegian Institute of Public Health was notified of a gastroenteritis outbreak following two meetings held at a conference centre. Identical food and beverages were served during the meetings. We investigated in order to identify the vehicle of infection and implement control measures. Meeting participants completed an online questionnaire on consumption of foods and beverages. We asked symptomatic participants to provide a stool sample. We defined a case as diarrhoea and/or vomiting in a participant who became ill within 3 days after the meeting. We calculated attack rates (AR) and adjusted risk ratios (aRR) with 95% confidence intervals (CI) using binomial regression. We conducted environmental investigations. Overall, 147/168 (88%) participants responded, of which 74 (50%) met the case definition. All five stool samples provided were norovirus positive. No kitchen staff reported being sick. Risk of illness was higher in those who consumed raspberry mousse (aRR 3.4, 95% CI 1.4 8.2) and sliced fresh fruit (aRR 1.9, 95% CI 1.3-2.8). Seventy cases (95%) ate raspberry mousse. Frozen raspberries used for the mousse were imported and not heat-treated before consumption. Non-heat-treated frozen raspberries were the most likely outbreak vehicle. Contamination by a food handler could not be excluded. We recommend heat-treatment of imported frozen berries before consumption. PMID- 26878753 TI - Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis. AB - Phosphorylation of histone H3 threonine 118 (H3 T118ph) weakens histone DNA contacts, disrupting the nucleosome structure. We show that Aurora-A mediated H3 T118ph occurs at pericentromeres and chromosome arms during prophase and is lost upon chromosome alignment. Expression of H3 T118E or H3 T118I (a SIN mutation that bypasses the need for the ATP-dependent nucleosome remodeler SWI/SNF) leads to mitotic problems including defects in spindle attachment, delayed cytokinesis, reduced chromatin packaging, cohesion loss, cohesin and condensin I loss in human cells. In agreement, overexpression of Aurora-A leads to increased H3 T118ph levels, causing cohesion loss, and reduced levels of cohesin and condensin I on chromatin. Normal levels of H3 T118ph are important because it is required for development in fruit flies. We propose that H3 T118ph alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation. PMID- 26878754 TI - Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction. AB - Women live on average longer than men but have greater levels of late-life morbidity. We have uncovered a substantial sex difference in the pathology of the aging gut in Drosophila. The intestinal epithelium of the aging female undergoes major deterioration, driven by intestinal stem cell (ISC) division, while lower ISC activity in males associates with delay or absence of pathology, and better barrier function, even at old ages. Males succumb to intestinal challenges to which females are resistant, associated with fewer proliferating ISCs, suggesting a trade-off between highly active repair mechanisms and late-life pathology in females. Dietary restriction reduces gut pathology in aging females, and extends female lifespan more than male. By genetic sex reversal of a specific gut region, we induced female-like aging pathologies in males, associated with decreased lifespan, but also with a greater increase in longevity in response to dietary restriction. PMID- 26878756 TI - Economic impact of electronic prescribing in the hospital setting: A systematic review. AB - OBJECTIVE: To examine evidence on the economic impact of electronic prescribing (EP) systems in the hospital setting. METHOD: We conducted a systematic search of MEDLINE, EMBASE, PsycINFO, International Pharmaceutical Abstracts, the NHS Economic Evaluation Database, the European Network of Health Economic Evaluation Database and Web of Science from inception to October 2013. Full and partial economic evaluations of EP or computerized provider order entry were included. We excluded studies assessing prescribing packages for specific drugs, and monetary outcomes that were not related to medicines. A checklist was used to evaluate risk of bias and evidence quality. RESULTS: The search yielded 1160 articles of which three met the inclusion criteria. Two were full economic evaluations and one a partial economic evaluation. A meta-analysis was not appropriate as studies were heterogeneous in design, economic evaluation method, interventions and outcome measures. Two studies investigated the financial impact of reducing preventable adverse drug events. The third measured savings related to various aspects of the system including those related to medication. Two studies reported positive financial effects. However the overall quality of the economic evidence was low and key details often not reported. DISCUSSION: There seems to be some evidence of financial benefits of EP in the hospital setting. However, it is not clear if evidence is transferable to other settings. Research is scarce and limited in quality, and reported methods are not always transparent. Further robust, high quality research is required to establish if hospital EP is cost effective and thus inform policy makers' decisions. PMID- 26878757 TI - Examining individuals' adoption of healthcare wearable devices: An empirical study from privacy calculus perspective. AB - BACKGROUND: Wearable technology has shown the potential of improving healthcare efficiency and reducing healthcare cost. Different from pioneering studies on healthcare wearable devices from technical perspective, this paper explores the predictors of individuals' adoption of healthcare wearable devices. Considering the importance of individuals' privacy perceptions in healthcare wearable devices adoption, this study proposes a model based on the privacy calculus theory to investigate how individuals adopt healthcare wearable devices. METHOD: The proposed conceptual model was empirically tested by using data collected from a survey. The sample covers 333 actual users of healthcare wearable devices. Structural equation modeling (SEM) method was employed to estimate the significance of the path coefficients. RESULTS: This study reveals several main findings: (1) individuals' decisions to adopt healthcare wearable devices are determined by their risk-benefit analyses (refer to privacy calculus). In short, if an individual's perceived benefit is higher than perceived privacy risk, s/he is more likely to adopt the device. Otherwise, the device would not be adopted; (2) individuals' perceived privacy risk is formed by health information sensitivity, personal innovativeness, legislative protection, and perceived prestige; and (3) individuals' perceived benefit is determined by perceived informativeness and functional congruence. The theoretical and practical implications, limitations, and future research directions are then discussed. PMID- 26878758 TI - Exploring the effects of patients taking a vigilant role in collaborating on their e-medication administration record. AB - OBJECTIVE: Errors in the electronic medication administration record (eMAR) occur in 25.6% of cases, mainly due to communication errors. The aim of this study is to investigate whether the quality of the eMAR improves when patients play a vigilant role by checking their medication using a patient communication tool linked to their eMAR (eMAR-PCT) to communicate asynchronously with the pharmacist about errors. Effects on health outcomes and self-care are also explored. METHODS: In this quasi-experimental study, polypharmacy patients using five or more medications were randomly selected and invited to use their eMAR-PCTs. Participants also received two digital questionnaires assessing health and self care (week 0 and 26). Statistical analyses were performed on two subgroups: eMAR PCT users and non-users. RESULTS: An inclusion rate of 43.5% (n=152) was achieved. Women were more prevalent than men among the users group (56.4% vs. 43.6%). Among the eMAR-PCT users, 75% logged in more than once, and 17.9% communicated asynchronously with the pharmacist. The content of the e-mails shows that eMAR-PCT was used as intended. No improvement in the quality of the eMAR was found. The self-care variables self-efficacy (p=.006) and collaboration with the pharmacist (p=.021) showed significant improvement in the users group. CONCLUSION AND DISCUSSION: The results showed no effect on eMAR quality and a modest improvement in self-care. Active digital patient participation to improve the quality of eMAR merits further investigation as, in line with other research, tentatively positive results are shown on self-care. Possibilities for implementation are promising as half of the patients who pledged to use eMAR-PCT actually did, and used it as intended. PMID- 26878759 TI - Residents' numeric inputting error in computerized physician order entry prescription. AB - BACKGROUND: Computerized physician order entry (CPOE) system with embedded clinical decision support (CDS) can significantly reduce certain types of prescription error. However, prescription errors still occur. Various factors such as the numeric inputting methods in human computer interaction (HCI) produce different error rates and types, but has received relatively little attention. OBJECTIVE: This study aimed to examine the effects of numeric inputting methods and urgency levels on numeric inputting errors of prescription, as well as categorize the types of errors. METHODS: Thirty residents participated in four prescribing tasks in which two factors were manipulated: numeric inputting methods (numeric row in the main keyboard vs. numeric keypad) and urgency levels (urgent situation vs. non-urgent situation). Multiple aspects of participants' prescribing behavior were measured in sober prescribing situations. RESULTS: The results revealed that in urgent situations, participants were prone to make mistakes when using the numeric row in the main keyboard. With control of performance in the sober prescribing situation, the effects of the input methods disappeared, and urgency was found to play a significant role in the generalized linear model. Most errors were either omission or substitution types, but the proportion of transposition and intrusion error types were significantly higher than that of the previous research. Among numbers 3, 8, and 9, which were the less common digits used in prescription, the error rate was higher, which was a great risk to patient safety. CONCLUSIONS: Urgency played a more important role in CPOE numeric typing error-making than typing skills and typing habits. It was recommended that inputting with the numeric keypad had lower error rates in urgent situation. An alternative design could consider increasing the sensitivity of the keys with lower frequency of occurrence and decimals. To improve the usability of CPOE, numeric keyboard design and error detection could benefit from spatial incidence of errors found in this study. PMID- 26878760 TI - Assessment of hospital processes using a process mining technique: Outpatient process analysis at a tertiary hospital. AB - INTRODUCTION: Many hospitals are increasing their efforts to improve processes because processes play an important role in enhancing work efficiency and reducing costs. However, to date, a quantitative tool has not been available to examine the before and after effects of processes and environmental changes, other than the use of indirect indicators, such as mortality rate and readmission rate. METHODS: This study used process mining technology to analyze process changes based on changes in the hospital environment, such as the construction of a new building, and to measure the effects of environmental changes in terms of consultation wait time, time spent per task, and outpatient care processes. Using process mining technology, electronic health record (EHR) log data of outpatient care before and after constructing a new building were analyzed, and the effectiveness of the technology in terms of the process was evaluated. RESULTS: Using the process mining technique, we found that the total time spent in outpatient care did not increase significantly compared to that before the construction of a new building, considering that the number of outpatients increased, and the consultation wait time decreased. These results suggest that the operation of the outpatient clinic was effective after changes were implemented in the hospital environment. We further identified improvements in processes using the process mining technique, thereby demonstrating the usefulness of this technique for analyzing complex hospital processes at a low cost. CONCLUSION: This study confirmed the effectiveness of process mining technology at an actual hospital site. In future studies, the use of process mining technology will be expanded by applying this approach to a larger variety of process change situations. PMID- 26878761 TI - Barriers and facilitators to exchanging health information: a systematic review. AB - OBJECTIVES: We conducted a systematic review of studies assessing facilitators and barriers to use of health information exchange (HIE). METHODS: We searched MEDLINE, PsycINFO, CINAHL, and the Cochrane Library databases between January 1990 and February 2015 using terms related to HIE. English-language studies that identified barriers and facilitators of actual HIE were included. Data on study design, risk of bias, setting, geographic location, characteristics of the HIE, perceived barriers and facilitators to use were extracted and confirmed. RESULTS: Ten cross-sectional, seven multiple-site case studies, and two before-after studies that included data from several sources (surveys, interviews, focus groups, and observations of users) evaluated perceived barriers and facilitators to HIE use. The most commonly cited barriers to HIE use were incomplete information, inefficient workflow, and reports that the exchanged information that did not meet the needs of users. The review identified several facilitators to use. DISCUSSION: Incomplete patient information was consistently mentioned in the studies conducted in the US but not mentioned in the few studies conducted outside of the US that take a collective approach toward healthcare. Individual patients and practices in the US may exercise the right to participate (or not) in HIE which effects the completeness of patient information available to be exchanged. Workflow structure and user roles are key but understudied. CONCLUSIONS: We identified several facilitators in the studies that showed promise in promoting electronic health data exchange: obtaining more complete patient information; thoughtful workflow that folds in HIE; and inclusion of users early in implementation. PMID- 26878763 TI - Design and implementation of a national public health surveillance system in Jordan. AB - Understanding and improving the health status of communities depend on effective public health surveillance. Adoption of new technologies, standardised case definitions and clinical guidelines for accurate diagnosis, and access to timely and reliable data, remains a challenge for public health surveillance systems however and existing public health surveillance systems are often fragmented, disease specific, inconsistent and of poor quality. We describe the application of an enterprise architecture approach to the design, planning and implementation of a national public health surveillance system in Jordan. This enabled a well planned and collaboratively supported system to be built and implemented using consistent standards for data collection, management, reporting and use. The system is case-based and integrated and employs mobile information technology to aid collection of real-time, standardised data to inform and improve decision making at different levels of the health system. PMID- 26878762 TI - Patient knowledge and information-seeking about personalized cancer therapy. AB - BACKGROUND: Understanding patients' knowledge and prior information-seeking regarding personalized cancer therapy (PCT) may inform future patient information systems, consent for molecular testing and PCT protocols. We evaluated breast cancer patients' knowledge and information-seeking behaviors regarding PCT. METHODS: Newly registered female breast cancer patients (n=100) at a comprehensive cancer center completed a self-administered questionnaire prior to their first clinic visit. RESULTS: Knowledge regarding cancer genetics and PCT was moderate (mean 8.7+/-3.8 questions correct out of 16). A minority of patients (27%) indicated that they had sought information regarding PCT. Higher education (p=0.009) and income levels (p=0.04) were associated with higher knowledge scores and with seeking PCT information (p=0.04). Knowledge was not associated with willingness to participate in PCT research. CONCLUSION: Educational background and financial status impact patient knowledge as well as information-seeking behavior. For most patients, clinicians are likely to be patients' initial source of information about PCT. Understanding patients' knowledge deficits at presentation may help inform patient education efforts. PMID- 26878764 TI - Impacts of mobile tablet computing on provider productivity, communications, and the process of care. AB - OBJECTIVE: Health information technology investments continue to increase while the value derived from their implementation and use is mixed. Mobile device adoption into practice is a recent trend that has increased dramatically and formal studies are needed to investigate consequent benefits and challenges. The objective of this study is to evaluate practitioner perceptions of improvements in productivity, provider-patient communications, care provision, technology usability and other outcomes following the adoption and use of a tablet computer connected to electronic health information resources. METHODS: A pilot program was initiated in June 2013 to evaluate the effect of mobile tablet computers at one health provider organization in the southeast United States. Providers were asked to volunteer for the evaluation and were each given a mobile tablet computer. A total of 42 inpatient and outpatient providers were interviewed in 2015 using a survey style questionnaire that utilized yes/no, Likert-style, and open ended questions. Each had previously used an electronic health record (EHR) system a minimum of one year outside of residency, and were regular users of personal mobile devices. Each used a mobile tablet computer in the context of their practice connected to the health system EHR. RESULTS: The survey results indicate that more than half of providers perceive the use of the tablet device as having a positive effect on patient communications, patient education, patient's perception of the provider, time spent interacting with patients, provider productivity, process of care, satisfaction with EHR when used together with the device, and care provision. Providers also reported feeling comfortable using the device (82.9%), would recommend the device to colleagues (69.2%), did not experience increased information security and privacy concerns (95%), and noted significant reductions in EHR login times (64.1%). Less than 25% of participants reported negative impacts on any of these areas as well as on time spent on order submission, note completion time, overall workload, patient satisfaction with care experience and patient outcomes. Gender, number of years in practice, practice type (general practitioner vs. specialist), and service type (inpatient/outpatient) were found to have a significant effect on perceptions of patient satisfaction, care process, and provider productivity. CONCLUSIONS: Providers found positive gains from utilizing mobile devices in overall productivity, improved communications with their patients, the process of care, and technology efficiencies when used in combination with EHR and other health information resources. Demographic and health care work environment play a role in how mobile technologies are integrated into practice by providers. PMID- 26878765 TI - The role of tablets in accessing information throughout undergraduate medical education in Botswana. AB - BACKGROUND: Mobile learning (mLearning) uses wireless networks and mobile devices to expand physician trainees' and healthcare providers' access to and exchange of medical information. Opportunities to increase implementation and expand use of mobile devices to support health care information access and delivery in Africa are vast, but the rapid growth of mLearning has caused project implementation to outpace objective measurement of impact. This study makes a contribution to the existing body of literature regarding mLearning implementation in Africa through its focus on the use of smart devices (tablets) in undergraduate medical education and medical students' perceptions of the effects on their learning environment. MATERIALS AND METHODS: The population of this prospective mixed methods study consisted of 82 undergraduate medical students (45 third year and 37 fourth year) at the University of Botswana Faculty of Medicine. They received tablets in the earliest phase of the mLearning project implementation (between November 2012 and January 2013), when they were in the third and fourth year of their medical training. Usage of the tablets was assessed both quantitatively and qualitatively, through both application usage tracking and focus groups. RESULTS: Based on application usage data and coding and analysis of focus group discussions, undergraduate medical students indicated that tablets were useful in their medical education, allowing them continual access to information and opportunities for communication. Participants noted that the primary barrier to use of tablets was the lack of mobile cellular Internet beyond the Wi-Fi zones at the training sites. Moreover, participants offered suggestions for improvements to the implementation process. CONCLUSIONS: Even in resource-limited settings where Internet access can be unreliable and intermittent, the adoption of tablets can have benefits to medical education by providing consistent access to extensive and current medical information resources. This study highlights the value of clinical resources with offline functionality, with or without consistent access to the Internet. There is also the potential for optimizing the use of tablets through improved training and technical support. PMID- 26878766 TI - Comparing usability testing outcomes and functions of six electronic nursing record systems. AB - OBJECTIVES: This study examined the usability of six differing electronic nursing record (ENR) systems on the efficiency, proficiency and available functions for documenting nursing care and subsequently compared the results to nurses' perceived satisfaction from a previous study. METHODS: The six hospitals had different ENR systems, all with narrative nursing notes in use for more than three years. Stratified by type of nursing unit, 54 staff nurses were digitally recorded during on-site usability testing by employing validated patient care scenarios and think-aloud protocols. The time to complete specific tasks was also measured. Qualitative performance data were converted into scores on efficiency (relevancy), proficiency (accuracy), and a competency index using scoring schemes described by McGuire and Babbott. Six nurse managers and the researchers completed assessments of available ENR functions and examined computerized nursing process components including the linkages among them. RESULTS: For the usability test, participants' mean efficiency score was 94.2% (95% CI, 91.4 96.9%). The mean proficiency was 60.6% (95% CI, 54.3-66.8%), and the mean competency index was 59.5% (95% CI, 52.9-66.0). Efficiency scores were significantly different across ENRs as was the time to complete tasks, ranging from 226.3 to 457.2s (chi(2)=12.3, P=0.031; chi(2)=11.2, P=0.048). No significant differences were seen for proficiency scores. The coverage of the various ENRs' nursing process ranged from 67% to 100%, but only two systems had complete integration of nursing components. Two systems with high efficiency and proficiency scores had much lower usability test scores and perceived user satisfaction along with more complex navigation patterns. CONCLUSIONS: In terms of system usability and functions, different levels of sophistication of and interaction performance with ENR systems exist in practice. This suggests that ENRs may have variable impacts on clinical outcomes and care quality. Future studies are needed to explore ENR impact on nursing care quality, efficiency, and safety. PMID- 26878767 TI - User perception and experience of the introduction of a novel critical care patient viewer in the ICU setting. AB - OBJECTIVE: Failure to rapidly identify high-value information due to inappropriate output may alter user acceptance and satisfaction. The information needs for different intensive care unit (ICU) providers are not the same. This can obstruct successful implementation of electronic medical record (EMR) systems. We evaluated the implementation experience and satisfaction of providers using a novel EMR interface-based on the information needs of ICU providers-in the context of an existing EMR system. METHODS: This before-after study was performed in the ICU setting at two tertiary care hospitals from October 2013 through November 2014. Surveys were delivered to ICU providers before and after implementation of the novel EMR interface. Overall satisfaction and acceptance was reported for both interfaces. RESULTS: A total of 246 before (existing EMR) and 115 after (existing EMR+novel EMR interface) surveys were analyzed. 14% of respondents were prescribers and 86% were non-prescribers. Non-prescribers were more satisfied with the existing EMR, whereas prescribers were more satisfied with the novel EMR interface. Both groups reported easier data gathering, routine tasks & rounding, and fostering of team work with the novel EMR interface. This interface was the primary tool for 18% of respondents after implementation and 73% of respondents intended to use it further. Non-prescribers reported an intention to use this novel interface as their primary tool for information gathering. CONCLUSION: Compliance and acceptance of new system is not related to previous duration of work in ICU, but ameliorates with the length of EMR interface usage. Task-specific and role-specific considerations are necessary for design and successful implementation of a EMR interface. The difference in user workflows causes disparity of the way of EMR data usage. PMID- 26878769 TI - The degenerative cervical spine. AB - Imaging techniques provide excellent anatomical images of the cervical spine. The choice to use one technique or another will depend on the clinical scenario and on the treatment options. Plain-film X-rays continue to be fundamental, because they make it possible to evaluate the alignment and bone changes; they are also useful for follow-up after treatment. The better contrast resolution provided by magnetic resonance imaging makes it possible to evaluate the soft tissues, including the intervertebral discs, ligaments, bone marrow, and spinal cord. The role of computed tomography in the study of degenerative disease has changed in recent years owing to its great spatial resolution and its capacity to depict osseous components. In this article, we will review the anatomy and biomechanical characteristics of the cervical spine, and then we provide a more detailed discussion of the degenerative diseases that can affect the cervical spine and their clinical management. PMID- 26878768 TI - Differences of immune responses between Tongcheng (Chinese local breed) and Large White pigs after artificial infection with highly pathogenic porcine reproductive and respiratory syndrome virus. AB - Porcine reproductive and respiratory syndrome (PRRS) is one of the severest infectious diseases of pigs throughout the world. Pigs of different breeds infected with PRRS virus (PRRSV) have been reported to vary in their immune responses. Here, the differences of immune responses to highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) were investigated by artificially infecting Tongcheng (TC) pigs (a Chinese indigenous breed) and Large White (LW) pigs with PRRSV WUH3. Compared to LW pigs, TC pigs showed less severe symptoms and lower level of viral load. The routine blood test results indicated that TC pigs were relatively steady in terms of erythrocyte, leukocyte and platelet. Additionally, PRRSV infection induced higher IFN-gamma activity in TC pigs, but stimulated an excessive level of IL-10 and IL-12p40 in LW pigs. Our study provides direct evidence that TC pigs have stronger resistance to early PRRSV infection than LW pigs, suggesting that the resistance of pigs to PRRSV is likely associated with breed differences. PMID- 26878771 TI - Characterisation of the biochemical methane potential (BMP) of individual material fractions in Danish source-separated organic household waste. AB - This study is dedicated to characterising the chemical composition and biochemical methane potential (BMP) of individual material fractions in untreated Danish source-separated organic household waste (SSOHW). First, data on SSOHW in different countries, available in the literature, were evaluated and then, secondly, laboratory analyses for eight organic material fractions comprising Danish SSOHW were conducted. No data were found in the literature that fully covered the objectives of the present study. Based on laboratory analyses, all fractions were assigned according to their specific properties in relation to BMP, protein content, lipids, lignocellulose biofibres and easily degradable carbohydrates (carbohydrates other than lignocellulose biofibres). The three components in lignocellulose biofibres, i.e. lignin, cellulose and hemicellulose, were differentiated, and theoretical BMP (TBMP) and material degradability (BMP from laboratory incubation tests divided by TBMP) were expressed. Moreover, the degradability of lignocellulose biofibres (the share of volatile lignocellulose biofibre solids degraded in laboratory incubation tests) was calculated. Finally, BMP for average SSOHW composition in Denmark (untreated) was calculated, and the BMP contribution of the individual material fractions was then evaluated. Material fractions of the two general waste types, defined as "food waste" and "fibre-rich waste," were found to be anaerobically degradable with considerable BMP. Material degradability of material fractions such as vegetation waste, moulded fibres, animal straw, dirty paper and dirty cardboard, however, was constrained by lignin content. BMP for overall SSOHW (untreated) was 404 mL CH4 per g VS, which might increase if the relative content of material fractions, such as animal and vegetable food waste, kitchen tissue and dirty paper in the waste, becomes larger. PMID- 26878770 TI - Chelating capture and magnetic removal of non-magnetic heavy metal substances from soil. AB - A soil remediation method based on magnetic beneficiation is reported. A new magnetic solid chelator powder, FS@IDA (core-shell Fe3O4@SiO2 nanoparticles coated with iminodiacetic acid chelators), was used as a reactive magnetic carrier to selectively capture non-magnetic heavy metals in soil by chelation and removal by magnetic separation. FS@IDA was prepared via inorganic-organic and organic synthesis reactions that generated chelating groups on the surface of magnetic, multi-core, core-shell Fe3O4@SiO2 (FS) nanoparticles. These reactions used a silane coupling agent and sodium chloroacetate. The results show that FS@IDA could chelate the heavy metal component of Cd, Zn, Pb, Cu and Ni carbonates, lead sulfate and lead chloride in water-insoluble salt systems. The resulting FS@IDA-Cd and FS@IDA-Pb chelates could be magnetically separated, resulting in removal rates of approximately 84.9% and 72.2% for Cd and Pb, respectively. FS@IDA could not remove the residual heavy metals and those bound to organic matter in the soil. FS@IDA did not significantly alter the chemical composition of the soil, and it allowed for fast chelating capture, simple magnetic separation and facilitated heavy metal elution. FS@IDA could also be easily prepared and reprocessed. PMID- 26878772 TI - Has a mixture of amino acids and micronutrients influence on glucose metabolism and dietary fatty acid pattern in chronic psychosocially stressed persons? A pilot study. AB - Brain food, e.g. L-tryptophan, antioxidative substances, B vitamins and magnesium are thought to be beneficial for obesity, inflammation and insulin resistance. In the present pilot study we hypothesised that a specific amino acid mixture with micronutrients improves the cardiometabolic situation of chronically stressed persons. Cardiovascular and metabolic parameters were analysed as per protocol in 32 patients. Chronic stress disorders in the same patients were assessed by a psychological neurological questionnaire (PNF). After dietary intervention a reduction of the fasting serum insulin concentrations occurred in the treatment group. An association was found between PNF values, insulin concentrations at baseline and an insulin reduction after 12 weeks. The results support the use of our specific dietary supplement for improved stress management and a decrease in metabolic dysfunction. PMID- 26878773 TI - Antioxidant tert-butylhydroquinone ameliorates arsenic-induced intracellular damages and apoptosis through induction of Nrf2-dependent antioxidant responses as well as stabilization of anti-apoptotic factor Bcl-2 in human keratinocytes. AB - Human skin is a known target site of inorganic arsenic with effects ranging from hyperkeratosis to dermal malignancies. Tert-butylhydroquinone (tBHQ), approved food-grade phenolic antioxidant, is demonstrated to induce remarkable antioxidant activity in a variety of cells and tissues. The present study aimed at the protective effects of tBHQ on arsenic-induced cytotoxicity and apoptosis in human keratinocytes. Our results demonstrated that tBHQ antagonized arsenic-induced decrease of cell viability, generation of reactive oxygen species (ROS) and lipid peroxidation, as well as reduction of antioxidative enzymes superoxide dismutase (SOD) and catalase (CAT) activities. We also found that tBHQ relieved the G2/M phase arrest by arsenic exposure, which was associated with altering the expression of cell cycle regulators cyclin D1 and CDK4. tBHQ treatment further reduced the numbers of arsenic-induced mitochondrial-mediated apoptotic cells, which occurred concomitantly with the effective recovery of mitochondrial membrane potential (DeltaPsim) depolarization, the release of cytochrome c releasing from the mitochondrial as well as the survival signal related factor caspase 3 activation. Our experiments then confirmed that tBHQ activated nuclear factor E2-related factor 2 (NRF2) pathway by increasing NRF2 protein in both nucleus and cytoplasm and upregulating NRF2 downstream targets NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). More interestingly, arsenic induced decrease of anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) and increase of pro-apoptotic factor Bcl-2-associated X protein (Bax) could all be reversed by tBHQ pretreatment. These results suggested together that tBHQ could ameliorate arsenic-induced cytotoxicity and apoptosis, which might be linked with the induction of Nrf2-dependent antioxidant responses as well as stabilization of anti-apoptotic factor Bcl-2 in human keratinocytes. PMID- 26878774 TI - Soluble receptor for advanced glycation end-products protects against ischemia/reperfusion-induced myocardial apoptosis via regulating the ubiquitin proteasome system. AB - AIM: Apoptosis participated in the pathological process of myocardial ischemia/reperfusion (I/R) injury. Previous studies have reported that endogenous substance sRAGE protect against I/R injury through inhibiting myocardial apoptosis. But the mechanisms are currently unknown. Prior work has demonstrated that ubiquitin proteasome system (UPS) dysfunction is closely related to apoptosis. We explored the potential role of UPS in the effect of sRAGE inhibition on I/R-induced myocardial apoptosis. METHODS AND RESULTS: Adult male C57BL mice treated with sRAGE (100MUg/day, i.p.) or saline were performed to ligate left anterior descending coronary artery (LAD) as an in vivo model. As an in vitro model, primary murine cardiomyocytes pretreated with sRAGE or sRAGE containing adenovirus were simulated I/R by "ischemia buffer". The TUNEL and caspase-3 activity were assessed. Also the activity and expression of proteasome were detected. sRAGE decreased the number of TUNEL-positive cardiomyocytes and caspase-3 activity, however, the inhibition of sRAGE on I/R-induced apoptosis was abolished by proteasome inhibitor Bortezimb (BTZ). sRAGE inhibited the decreased proteasome activity, also the reduction in protein and gene levels of beta1i and beta5i following I/R. Suppression of STAT3 blocked the inhibition of sRAGE on apoptosis induced by I/R. The chromatin immunoprecipitation (CHIP) results confirmed that sRAGE promoted activating STAT3 binding to beta1i and beta5i promoter. CONCLUSIONS: Our data suggest that the inhibition of sRAGE on I/R induced apoptosis is associated with activation and expression of proteasome, including improved proteasome activity and elevated beta1i and beta5i expression mediated by STAT3 activation. We predict that sRAGE is a novel intervention to target UPS activation for preventing and treating myocardial apoptosis. PMID- 26878775 TI - Directly interact with Keap1 and LPS is involved in the anti-inflammatory mechanisms of (-)-epicatechin-3-gallate in LPS-induced macrophages and endotoxemia. AB - Disruption of the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) interaction has emerged as a promising strategy to reduce oxidative stress-induced inflammation. However, its roles in regulating downstream events, including the cross talk between Nrf2 and nuclear factor-kappa B (NF-kappaB), are not well defined. The objective of this study was to elucidate the mechanistic connection between Keap1-Nrf2 signaling and the transcription factor NF-kappaB and to investigate the function of (-) epicatechin-3-gallate (ECG) in the repression of multiple inflammatory mediators. ECG attenuated lipopolysaccharide (LPS)-induced inflammatory mediator expression and intracellular reactive oxygen species (ROS) generation through the induction of Nrf2/antioxidant response element (ARE)-driven glutathione (GSH) and hemeoxygenase-1 (HO-1) levels, interference with NF-kappaB and Nfr2/ARE transcriptional activities, and suppression of the MAPKs (JNK1/2 and p38) and PI3K/Akt signaling pathways. Importantly, anti-inflammatory effects of ECG partly require activation of ERK1/2 signaling to mediate HO-1 expression and Nrf2/ARE signaling activation. Furthermore, ECG may directly interact intracellularly with the Kelch repeat domains of Keap1 and bind to extracellular LPS, thereby promoting the nuclear accumulation of the Nrf2 protein and blockading the activation of LPS-induced downstream target signaling pathways. Consistent with in vitro studies, ECG attenuates pathological syndromes of LPS-induced sepsis and systemic inflammation. Our results identified ECG as a novel Keap1-Nrf2 interaction disruptor and LPS-induced TLR4 activation inhibitor, thereby providing an innovative strategy to prevent or treat immune, oxidative stress and inflammatory-related diseases. PMID- 26878776 TI - Interpolation method for accurate affinity ranking of arrayed ligand-analyte interactions. AB - The values of the affinity constants (kd, ka, and KD) that are determined by label-free interaction analysis methods are affected by the ligand density. This article outlines a surface plasmon resonance (SPR) imaging method that yields high-throughput globally fitted affinity ranking values using a 96-plex array. A kinetic titration experiment without a regeneration step has been applied for various coupled antibodies binding to a single antigen. Globally fitted rate (kd and ka) and dissociation equilibrium (KD) constants for various ligand densities and analyte concentrations are exponentially interpolated to the KD at Rmax = 100 RU response level (KD(R100)). PMID- 26878777 TI - Prevention of arterial thrombosis by nobiletin: in vitro and in vivo studies. AB - Nobiletin, a bioactive polymethoxylated flavone isolated from citrus fruits, has been proven to prevent cancer and inflammation. Dietary flavonoids have been shown to reduce the risk of cardiovascular diseases (CVDs), and platelet activation plays a crucial role in CVDs. This study investigated the effect of nobiletin on platelet activation in vitro and in vivo. Nobiletin (10-30MUM) inhibited collagen- and arachidonic acid-induced platelet aggregation in washed human platelets, but it did not inhibit platelet aggregation induced by other agonists such as thrombin and 9,11-dideoxy-11alpha,9alpha epoxymethanoprostaglandin. Nobiletin inhibited the phosphorylation of phospholipase PLCgamma2, protein kinase PKC, Akt and mitogen-activated protein kinase MAPKs in collagen-activated human platelets and markedly reduced intracellular calcium mobilization and hydroxyl radical (OH(.)) formation. Nobiletin did not affect either phorbol-12,13-dibutyrate-stimulated PKC activation or platelet aggregation. In addition, neither SQ22536, an adenylate cyclase inhibitor nor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, significantly reversed the nobiletin-mediated inhibition of platelet aggregation. Moreover, nobiletin substantially prolonged the closure time in whole blood according to platelet function analysis and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, this study demonstrates for the first time that, in addition to being a potential agent for preventing tumor growth and inflammation, nobiletin exhibits potent antiplatelet activity, which initially inhibits the PLCgamma2/PKC cascade and hydroxyl radical formation, subsequently suppresses the activation of Akt and MAPKs and ultimately inhibits platelet activation. Our study suggests that nobiletin represents a potential therapeutic agent for preventing or treating thromboembolic disorders. PMID- 26878778 TI - Astaxanthin reduces hepatic lipid accumulations in high-fat-fed C57BL/6J mice via activation of peroxisome proliferator-activated receptor (PPAR) alpha and inhibition of PPAR gamma and Akt. AB - We have previously reported that astaxanthin (AX), a dietary carotenoid, directly interacts with peroxisome proliferator-activated receptors PPARalpha and PPARgamma, activating PPARalpha while inhibiting PPARgamma, and thus reduces lipid accumulation in hepatocytes in vitro. To investigate the effects of AX in vivo, high-fat diet (HFD)-fed C57BL/6J mice were orally administered AX (6 or 30mg/kg body weight) or vehicle for 8weeks. AX significantly reduced the levels of triglyceride both in plasma and in liver compared with the control HFD mice. AX significantly improved liver histology and thus reduced both steatosis and inflammation scores of livers with hematoxylin and eosin staining. The number of inflammatory macrophages and Kupffer cells were reduced in livers by AX administration assessed with F4/80 staining. Hepatic PPARalpha-responsive genes involved in fatty acid uptake and beta-oxidation were upregulated, whereas inflammatory genes were downregulated by AX administration. In vitro radiolabeled assays revealed that hepatic fatty acid oxidation was induced by AX administration, whereas fatty acid synthesis was not changed in hepatocytes. In mechanism studies, AX inhibited Akt activity and thus decreased SREBP1 phosphorylation and induced Insig-2a expression, both of which delayed nuclear translocation of SREBP1 and subsequent hepatic lipogenesis. Additionally, inhibition of the Akt-mTORC1 signaling axis by AX stimulated hepatic autophagy that could promote degradation of lipid droplets. These suggest that AX lowers hepatic lipid accumulation in HFD-fed mice via multiple mechanisms. In addition to the previously reported differential regulation of PPARalpha and PPARgamma, inhibition of Akt activity and activation of hepatic autophagy reduced hepatic steatosis in mouse livers. PMID- 26878779 TI - Extra virgin olive oil rich in polyphenols modulates VEGF-induced angiogenic responses by preventing NADPH oxidase activity and expression. AB - Previous studies have shown the antiinflammatory, antioxidant and antiangiogenic properties by pure olive oil polyphenols; however, the effects of olive oil phenolic fraction on the inflammatory angiogenesis are unknown. In this study, we investigated the effects of the phenolic fraction (olive oil polyphenolic extract, OOPE) from extra virgin olive oil and related circulating metabolites on the VEGF-induced angiogenic responses and NADPH oxidase activity and expression in human cultured endothelial cells. We found that OOPE (1-10 MUg/ml), at concentrations achievable nutritionally, significantly reduced, in a concentration-dependent manner, the VEGF-induced cell migration, invasiveness and tube-like structure formation through the inhibition of MMP-2 and MMP-9. OOPE significantly (P<0.05) reduced VEGF-induced intracellular reactive oxygen species by modulating NADPH oxidase activity, p47phox membrane translocation and the expression of Nox2 and Nox4. Moreover, the treatment of endothelial cells with serum obtained 4 h after acute intake of extra virgin olive oil, with high polyphenol content, decreased VEGF-induced NADPH oxidase activity and Nox4 expression, as well as, MMP-9 expression, as compared with fasting control serum. Overall, native polyphenols and serum metabolites of extra virgin olive oil rich in polyphenols are able to lower the VEGF-induced angiogenic responses by preventing endothelial NADPH oxidase activity and decreasing the expression of selective NADPH oxidase subunits. Our results provide an alternative mechanism by which the consumption of olive oil rich in polyphenols may account for a reduction of oxidative stress inflammatory-related sequelae associated with chronic degenerative diseases. PMID- 26878780 TI - Short-term consumption of n-3 PUFAs increases murine IL-5 levels, but IL-5 is not the mechanistic link between n-3 fatty acids and changes in B-cell populations. AB - N-3 polyunsaturated fatty acids (PUFAs) exert immunomodulatory effects on B cells. We previously demonstrated that n-3 PUFAs enhanced the relative percentage and/or frequency of select B2 cell subsets. The objectives here were to determine if n-3 PUFAs (a) could boost cytokines that target B-cell frequency, (b) enhance the frequency of the B1 population and (c) to identify the mechanism by which n-3 PUFAs modify the proportion of B cells. Administration of n-3 PUFAs as fish oil to C57BL/6 mice enhanced secretion of the Th2 cytokine IL-5 but not IL-9 or IL 13. N-3 PUFAs had no influence on the percentage or frequency of peritoneal B1 or B2 cells. Subsequent experiments with IL-5(-/-) knockout mice showed n-3 PUFAs decreased the percentage of bone marrow B220(lo)IgM(hi) cells and increased the proportion and number of splenic IgM(+)IgD(lo)CD21(lo) cells compared to the control. These results, when compared with our previous findings with wild-type mice, suggested IL-5 had no role in mediating the effect of n-3 PUFAs on B-cell populations. To confirm this conclusion, we assayed IL-5 secretion in a diet induced obesity model in which n-3 PUFAs enhanced the frequency of select B-cell subsets. N-3 PUFA supplementation as ethyl esters to obesogenic diets did not alter circulating IL-5 levels. Altogether, the data establish that n-3 PUFAs as fish oil can increase circulating IL-5 in lean mice, which has implications for several disease end points, but this increase in IL-5 is not the mechanistic link between n-3 PUFAs and changes in B-cell populations. PMID- 26878782 TI - A nutritional nonalcoholic steatohepatitis minipig model. AB - BACKGROUND AND AIMS: The objective of this study was to elucidate whether a Western diet was associated with nonalcoholic steatohepatitis (NASH), and the relationship between NASH, autophagy and endoplasmic reticulum (ER) stress. METHODS: Four-month-old Lee-Sung minipigs were randomly assigned to two groups: control diet (C) and Western diet (W), for a 5-month experimental period. RESULTS: Feeding a Western diet produced a body composition with more fat, less lean and a greater liver weight. Compared with C pigs, W pigs also exhibited an elevated level of plasma insulin and free fatty acid. The W pigs displayed glucose intolerance, lower circulation antioxidant capacity and greater hepatic oxidative stress. Furthermore, pig fed the W diets had increased collagen accumulation in the liver and elevated systemic inflammation [tumor necrosis factor alpha and interleukin (IL)-6]. Compared with C pigs, W pigs had higher hepatic ER stress-related protein expression of GRP94, CHOP and caspase-12. The W pigs also had greater hepatic autophagy-related protein expression of p62 and LC3II. In an obesity antibody array analysis, W pigs had higher type 2 diabetes mellitus- (insulin-like growth factor 1, osteoprotegerin and resistin), atherosclerosis- (vascular endothelial growth factor, platelet-derived growth factor-AA and plasminogen activator inhibitor-I) and inflammation- [IL-1, macrophage-stimulating protein alpha, X-linked ectodermal dysplasia receptor and serum amyloid A (SAA)] related protein expressions. In addition, W pigs had greater plasma SAA concentration than C pigs and plasma SAA level was highly associated with IL-6. CONCLUSIONS: We successfully established a NASH pig model, and our findings suggested an association of NASH with ER stress and autophagy. The SAA has potential as a novel plasma biomarker for nonalcoholic fatty liver disease pigs. PMID- 26878781 TI - Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in Apc(Min) mouse model. AB - Colon cancer ranks third in cancer-related mortalities in the United States. Many studies have investigated factors that contribute to colon cancer in which dietary and environmental factors have been shown to play an integral role in the etiology of this disease. Specifically, human dietary intake of environmental carcinogens such as polycyclic aromatic hydrocarbons has generated interest in looking at how it exerts its effects in gastrointestinal carcinogenesis. Therefore, the objective of this study was to investigate the preventative effects of olive oil on benzo(a)pyrene [B(a)P]-induced colon carcinogenesis in adult Apc(Min) mice. Mice were assigned to a control (n=8) or treatment group (n=8) consisting of 25, 50 and 100-MUg B(a)P/kg body weight (bw) dissolved in tricaprylin [B(a)P-only group] or olive oil daily via oral gavage for 60 days. Our studies showed that Apc(Min) mice exposed to B(a)P developed a significantly higher number (P<0.05) of larger dysplastic adenomas compared to those exposed to B(a)P + olive oil. Treatment of mice with B(a)P and olive oil significantly altered (P<0.05) the expression of drug-metabolizing enzymes in both the colon and liver tissues. However, only GST activity was significantly higher (P<0.05) in the liver of mice treated with 50- and 100-MUg B(a)P/kg bw + olive oil. Lastly, olive oil promoted rapid detoxification of B(a)P by decreasing its organic metabolite concentrations and also decreasing the extent of DNA damage to colon and liver tissues (P<0.05). These results suggest that olive oil has a protective effect against B(a)P-induced colon tumors. PMID- 26878783 TI - Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases. AB - Understanding how dietary components alter the healthy baseline colonic microenvironment is important in determining their roles in influencing gut health and gut-associated diseases. Dietary flaxseed (FS) has demonstrated anti colon cancer effects in numerous rodent models, however, exacerbated acute colonic mucosal injury and inflammation in a colitis model. This study investigates whether FS alters critical aspects of gut health in healthy unchallenged mice, which may help explain some of the divergent effects observed following different gut-associated disease challenges. Four-week-old C57Bl/6 male mice were fed an AIN-93G basal diet (BD) or an isocaloric BD+10% ground FS diet for 3 weeks. FS enhanced colon goblet cell density, mucus production, MUC2 mRNA expression, and cecal short chain fatty acid levels, indicative of beneficial intestinal barrier integrity responses. Additionally, FS enhanced colonic regenerating islet-derived protein 3 gamma (RegIIIgamma) and reduced MUC1 and resistin-like molecule beta (RELMbeta) mRNA expression which may indicate altered responses in regulating microbial defense and injury repair responses. FS diet altered the fecal microbial community structure (16S rRNA gene profiling), including a 20-fold increase in Prevotella spp. and a 30-fold reduction in Akkermansia muciniphila abundance. A 10-fold reduction in A. muciniphila abundance by FS was also demonstrated in the colon tissue-associated microbiota (quantitative PCR). Furthermore, fecal branched chain fatty acids were increased by FS, indicative of increased microbial-derived putrefactive compounds. In conclusion, consumption of a FS-supplemented diet alters the baseline colonic microenvironment of healthy mice which may modify subsequent mucosal microbial defense and injury-repair responses leading to altered susceptibility to different gut-associated diseases. PMID- 26878784 TI - Treatment with kaempferol suppresses breast cancer cell growth caused by estrogen and triclosan in cellular and xenograft breast cancer models. AB - As a phytoestrogen, kaempferol (Kaem) is one of bioflavonoids, which are found in a variety of vegetables including broccoli, tea and tomato. In this study, the antiproliferative effects of Kaem in triclosn (TCS)-induced cell growth were examined in MCF-7 breast cancer cells. TCS promoted the cell viability of MCF-7 cells via estrogen receptor alpha (ERalpha) as did 17beta-estradiol (E2), a positive control. On the other hand, Kaem significantly suppressed E2 or TCS induced cell growth. To elucidate the molecular mechanisms of TCS and Kaem, alterations in the expressions of cell cycle, apoptosis and metastasis-related genes were identified using western blot assay. The treatment of the cells with TCS up-regulated the protein expressions of cyclin D1, cyclin E and cathepsin D, while down-regulated p21 and bax expressions. Kaem reversed TCS-induced gene expressions in an opposite manner. The phosphorylation of IRS-1, AKT, MEK1/2 and ERK was increased by TCS, indicating that TCS induced MCF-7 cell proliferation via nongenomic ER signaling pathway associated with IGF-1R. Kaem presented an antagonistic activity on this signaling by down-regulating the protein expression of pIRS-1, pAkt and pMEK1/2 promoted by E2 or TCS. In an in vivo xenografted mouse model, tumor growth was induced by treatment with E2 or TCS, which was identified in the measurement of tumor volume, hematoxylin and eosin staining, bromodeoxyuridine and immunohistochemistry assay. On the contrary, E2 or TCS induced breast tumor growth was inhibited by co-treatment with Kaem, which is consistent with in vitro results. Taken together, these results revealed that Kaem has an anticancer effect against procancer activity of E2 or TCS, a xenoestrogen, in breast cancer and may be suggested as a prominent agent to neutralize breast cancer risk caused by TCS. PMID- 26878785 TI - MicroRNA changes, activation of progenitor cells and severity of liver injury in mice induced by choline and folate deficiency. AB - Dietary deficiency in methyl-group donors and cofactors induces liver injury that resembles many pathophysiological and histopathological features of human nonalcoholic fatty liver disease (NAFLD), including an altered expression of microRNAs (miRNAs). We evaluated the consequences of a choline- and folate deficient (CFD) diet on the expression of miRNAs in the livers of male A/J and WSB/EiJ mice. The results demonstrate that NAFLD-like liver injury induced by the CFD diet in A/J and WSB/EiJ mice was associated with marked alterations in hepatic miRNAome profiles, with the magnitude of miRNA expression changes being greater in WSB/EiJ mice, the strain characterized by the greatest severity of liver injury. Specifically, WSB/EiJ mice exhibited more prominent changes in the expression of common miRNAs as compared to A/J mice and distinct miRNA alterations, including the overexpression of miR-134, miR-409-3p, miR-410 and miR 495 miRNAs that were accompanied by an activation of hepatic progenitor cells and fibrogenesis. This in vivo finding was further confirmed by in vitro experiments showing an overexpression of these miRNAs in undifferentiated progenitor hepatic HepaRG cells compared to in fully differentiated HepaRG cells. Additionally, a marked elevation of miR-134, miR-409-3p, miR-410 and miR-495 was found in plasma of WSB/EiJ mice fed the CFD diet, while none of the miRNAs was changed in plasma of A/J mice. These findings suggest that miRNAs may be crucial regulators responsible for the progression of NAFLD and may be useful as noninvasive diagnostic indicators of the severity and progression of NAFLD. PMID- 26878786 TI - Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats. AB - Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-alpha, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs. PMID- 26878787 TI - Preventive and therapeutic effects of blueberry (Vaccinium corymbosum) extract against DSS-induced ulcerative colitis by regulation of antioxidant and inflammatory mediators. AB - Inflammatory bowel disease (IBD) is an inflammatory disorder caused by hyperactivation of effector immune cells that produce high levels of proinflammatory cytokines. The aims of our study were to determine whether orally administered blueberry extract (BE) could attenuate or prevent the development of experimental colitis in mice and to elucidate the mechanism of action. Female Balb/C mice (n=7) were randomized into groups differing in treatment conditions (prevention and treatment) and dose of BE (50 mg/kg body weight). Acute ulcerative colitis was induced by oral administration of 3% dextran sodium sulfate for 7 days in drinking water. Colonic mucosal injury was assessed by clinical, macroscopic, biochemical and histopathological examinations. BE significantly decreased disease activity index and improved the macroscopic and histological score of colons when compared to the colitis group (P<.05). BE markedly attenuated myeloperoxidase accumulation (colitis group 54.97+/-2.78 nmol/mg, treatment group 30.78+/-1.33 nmol/mg) and malondialdehyde in colon and prostaglandin E2 level in serum while increasing the levels of superoxide dismutase and catalase (colitis group 11.94+/-1.16 U/ml, BE treatment group 16.49+/-0.39 U/ml) compared with the colitis group (P<.05). mRNA levels of the cyclooxygenase (COX)-2, interferon-gamma, interleukin (IL)-1beta and inducible nitric oxide synthase cytokines were determined by reverse transcriptase polymerase chain reaction. Immunohistochemical analysis showed that BE attenuates the expression of COX-2 and IL-1beta in colonic tissue. Moreover, BE reduced the nuclear translocation of nuclear transcription factor kappa B (NF-kappaB) by immunofluorescence analysis. Thus, the anti-inflammatory effect of BE at colorectal sites is a result of a number of mechanisms: antioxidation, down regulation of the expression of inflammatory mediators and inhibition of the nuclear translocation of NF-kappaB. PMID- 26878788 TI - Clinical phenotype clustering in cardiovascular risk patients for the identification of responsive metabotypes after red wine polyphenol intake. AB - This study aims to evaluate the robustness of clinical and metabolic phenotyping through, for the first time, the identification of differential responsiveness to dietary strategies in the improvement of cardiometabolic risk conditions. Clinical phenotyping of 57 volunteers with cardiovascular risk factors was achieved using k-means cluster analysis based on 69 biochemical and anthropometric parameters. Cluster validation based on Dunn and Figure of Merit analysis for internal coherence and external homogeneity were employed. k-Means produced four clusters with particular clinical profiles. Differences on urine metabolomic profiles among clinical phenotypes were explored and validated by multivariate orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) models. OSC-PLS-DA of (1)H-NMR data revealed that model comparing "obese and diabetic cluster" (OD-c) against "healthier cluster" (H-c) showed the best predictability and robustness in terms of explaining the pairwise differences between clusters. Considering these two clusters, distinct groups of metabolites were observed following an intervention with wine polyphenol intake (WPI; 733 equivalents of gallic acid/day) per 28days. Glucose was significantly linked to OD-c metabotype (P<.01), and lactate, betaine and dimethylamine showed a significant trend. Tartrate (P<.001) was associated with wine polyphenol intervention (OD-c_WPI and H-c_WPI), whereas mannitol, threonine methanol, fucose and 3-hydroxyphenylacetate showed a significant trend. Interestingly, 4 hydroxyphenylacetate significantly increased in H-c_WPI compared to OD-c_WPI and to basal groups (P<.05)-gut microbial-derived metabolite after polyphenol intake , thereby exhibiting a clear metabotypic intervention effect. Results revealed gut microbiota responsive phenotypes to wine polyphenols intervention. Overall, this study illustrates a novel metabolomic strategy for characterizing interindividual responsiveness to dietary intervention and identification of health benefits. PMID- 26878789 TI - High-salt diets during pregnancy increases renal vascular reactivity due to altered soluble guanylyl cyclase-related pathways in rat offspring. AB - Adverse prenatal factors such as overtake of salt or fat food are potential risks for cardiovascular diseases in offspring. This study tested the hypothesis that prenatal high-salt (HS) diets may influence renal vascular tone and attenuates signaling pathways related to soluble guanylyl cyclase (sGC) or/and large conductance Ca(2+)-activated K(+) (BKCa) channels in the offspring. Pregnant rats were fed either normal salt (NS) (1% NaCl) or HS (8% NaCl) diet for the whole gestation. Offspring were maintained on NS diets. Renal interlobar arteries in offspring were tested for vascular responses to phenylephrine (Phe), K(+) channels and signal pathways related to sGC. Phe induced higher vessel tension in interlobar arteries of the HS offspring. Following pretreatment with BKCa channel inhibitor iberiotoxin, Phe-mediated vasoconstrictions were decreased in HS offspring compared to NS. Phe-mediated constrictions following pretreatment with NO synthase inhibitor N(G)-nitro-l-arginine methyl ester or sGC inhibitor 1H 1,2,4-oxadiazolo-4,3-quinoxalin-1-one in the HS offspring were less sensitive than NS. The whole-cell K(+) currents and the component of BKCa channels were not changed in smooth muscle cells from interlobar arteries, whereas the K(+) currents stimulated by sGC activator BAY41-2272 were reduced in the HS offspring. The protein expressions of sGC beta1 and beta2 in the interlobar arteries of HS offspring were reduced. The results showed that chronic overintake of salt during pregnancy could increase renal vascular tone in the offspring. The affected signal pathways included down-regulation of sGC function and expression. PMID- 26878791 TI - Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system. AB - We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6 OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD. PMID- 26878790 TI - Diets enriched with cranberry beans alter the microbiota and mitigate colitis severity and associated inflammation. AB - Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmbeta and Reg3gamma gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1 3, Relmbeta, and Reg3gamma) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1beta, IL-6, IFNgamma and TNFalpha). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies. PMID- 26878792 TI - The combination of conjugated linoleic acid (CLA) and extra virgin olive oil increases mitochondrial and body metabolism and prevents CLA-associated insulin resistance and liver hypertrophy in C57Bl/6 mice. AB - Clinical conditions associated with obesity can be improved by daily intake of conjugated linoleic acid (CLA) or extra virgin olive oil (EVOO). Here we investigated whether dietary supplementation with CLA and EVOO, either alone or in combination, changes body metabolism associated with mitochondrial energetics. Male C57Bl/6 mice were divided into one of four groups: CLA (1:1 cis-9, trans 11:trans-10, cis-12; 18:2 isomers), EVOO, CLA plus EVOO or control (linoleic acid). Each mouse received 3 g/kg body weight of the stated oil by gavage on alternating days for 60 days. Dietary supplementation with CLA, alone or in combination with EVOO: (a) reduced the white adipose tissue gain; (b) increased body VO2 consumption, VCO2 production and energy expenditure; (c) elevated uncoupling protein (UCP)-2 expression and UCP activity in isolated liver mitochondria. This organelle, when energized with NAD(+)-linked substrates, produced high amounts of H2O2 without inducing oxidative damage. Dietary supplementation with EVOO alone did not change any metabolic parameter, but supplementation with CLA itself promoted insulin resistance and elevated weight, lipid content and acetyl-CoA carboxylase-1 expression in liver. Interestingly, the in vivo antioxidant therapy with N-acetylcysteine abolished the CLA-induced rise of body metabolism and liver UCP expression and activity, while the in vitro antioxidant treatment with catalase mitigated the CLA-dependent UCP-2 expression in hepatocytes; these findings suggest the participation of an oxidative dependent pathway. Therefore, this study clarifies the mechanisms by which CLA induces liver UCP expression and activity, and demonstrates for the first time the beneficial effects of combined CLA and EVOO supplementation. PMID- 26878793 TI - Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. AB - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors improve prognosis in patients with post-myocardial infarction (MI) related cardiac dysfunction. Resveratrol is a polyphenol that has been reported to be beneficial in hypertension, ischemic heart disease, and cardiotoxicity in preclinical studies. Accordingly, we investigated the comparative and combinatorial efficacy of resveratrol and perindopril (ACE inhibitor) treatment on MI-related cardiac remodeling and contractile dysfunction. METHODS: Left anterior descending artery ligated and sham-operated male Sprague-Dawley rats were gavaged with vehicle, resveratrol, perindopril, and combination of resveratrol+perindopril (2.5 mg/kg bodyweight/day) for 8 weeks (starting immediately after acute MI). Echocardiography was performed to assess cardiac structure and function at baseline and 8 weeks. RESULTS: At 8 weeks, vehicle-MI rats had a significantly lower left ventricular ejection fraction (LVEF) and increased LV dilatation compared to vehicle-sham rats. MI rats treated with resveratrol, perindopril and a combination of both had significantly improved LVEF and reduced LV dilatation. Vehicle-treated MI rats also had increased level of lipid peroxidation product- malondialdehyde (MDA), proinflammatory protein- tumor necrosis factor-alpha (TNF alpha) and cardiac fibrosis marker- collagen and decreased enzymatic activity of superoxide dismutase and catalase compared to vehicle-sham rats. Resveratrol, perindopril and combination of both significantly prevented the /ed to determine systolic functional parameter increase in MDA, TNF-alpha and collagen and improved the activity of superoxide dismutase and catalase in MI rats compared to vehicle-MI rats. CONCLUSION: Treatment with resveratrol or perindopril was equivalent in significantly improving remodeling and attenuation of contractile dysfunction in MI rats. Combination treatment also attenuated the cardiac abnormalities. The improvement in cardiac abnormalities may partly be through reducing oxidative stress by preventing the decrease in the activity of superoxide dismutase and catalase, and decreasing cardiac inflammation and fibrosis. PMID- 26878795 TI - Fisetin, a dietary flavonoid, ameliorates experimental colitis in mice: Relevance of NF-kappaB signaling. AB - Fisetin, a dietary flavonoid, is commonly found in many fruits and vegetables. Although studies indicate that fisetin has an anti-inflammatory property, little is known about its effects on intestinal inflammation. The present study investigated the effects of the fisetin on dextran sulphate sodium (DSS)-induced murine colitis, an animal model that resembles human inflammatory bowel disease. Fisetin treatment to DSS-exposed mice significantly reduced the severity of colitis and alleviated the macroscopic and microscopic signs of the disease. Moreover, fisetin reduced the levels of myeloperoxidase activity, the production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) and interleukin-6 (IL-6) and the expressions of COX 2 and iNOS in the colon tissues. Further studies revealed that fisetin suppressed the activation of NF-kappaB (p65) by inhibiting IkappaBalpha phosphorylation and NF-kappaB (p65)-DNA binding activity and attenuated the phosphorylation of Akt and the p38, but not ERK and JNK MAPKs in the colon tissues of DSS-exposed mice. In addition, DSS-induced decline in reduced glutathione (GSH) and the increase in malondialdehyde (MDA) levels were significantly restored by oral fisetin. Furthermore, the results from in vitro studies showed that fisetin significantly reduced the pro-inflammatory cytokine and mediator release and suppressed the degradation and phosphorylation of IkappaBalpha with subsequent nuclear translocation of NF-kappaB (p65) in lipopolysaccharide (LPS)-stimulated mouse primary peritoneal macrophages. These results suggest that fisetin exerts anti inflammatory activity via inhibition of Akt, p38 MAPK and NF-kappaB signaling in the colon tissues of DSS-exposed mice. Thus, fisetin may be a promising candidate as pharmaceuticals or nutraceuticals in the treatment of inflammatory bowel disease. PMID- 26878794 TI - EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-kappaB target genes in human endothelial cells. AB - Anti-inflammatory polyphenols, such as epigallocatechin-3-gallate (EGCG), have been shown to protect against the toxicity of environmental pollutants. It is well known that bioactive food compounds such as polyphenols may exert their protection by modulating inflammatory pathways regulated through nuclear factor kappa B (NF-kappaB) signaling. EGCG has been reported to inhibit NF-kappaB activation. We hypothesize that EGCG can protect against polychlorinated biphenyl (PCB)-induced endothelial inflammation in part through epigenetic regulation of NF-kappaB-regulated inflammatory genes. In order to test this hypothesis, human endothelial cells (EA.hy926) were exposed to physiologically relevant levels of coplanar PCB 126 and/or 15 or 30 MUM of EGCG, followed by quantification of NF kappaB subunit p65, histone acetyltransferase p300 and histone deacetylases (HDACs) accumulation through chromatin immunoprecipitation assay in the promoter region of inflammatory genes. In addition, the enrichment of the acetylated H3 was also quantified. PCB 126 exposure increased the expression of vascular inflammatory mediators, including interleukin (IL)-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and IL 1alpha/beta, which were prevented by pretreatment with EGCG. This inhibitory effect by EGCG correlated with abolished nuclear import of p65, decreased chromatin binding of p65 and p300, as well as increased chromatin binding of HDAC 1/2. Furthermore, EGCG induced hypoacetylation of H3, which accounts for deactivation of downstream genes. These data suggest that EGCG-induced epigenetic modifications can decrease PCB-induced vascular toxicity. PMID- 26878796 TI - Cinnamon intake alleviates the combined effects of dietary-induced insulin resistance and acute stress on brain mitochondria. AB - Insulin resistance (IR), which is a leading cause of the metabolic syndrome, results in early brain function alterations which may alter brain mitochondrial functioning. Previously, we demonstrated that rats fed a control diet and submitted to an acute restraint stress exhibited a delayed mitochondrial permeability transition pore (mPTP) opening. In this study, we evaluated the combined effects of dietary and emotional stressors as found in western way of life. We studied, in rats submitted or not to an acute stress, the effects of diet-induced IR on brain mitochondria, using a high fat/high fructose diet (HF(2)), as an IR inducer, with addition or not of cinnamon as an insulin sensitizer. We measured Ca(2+) retention capacity, respiration, ROS production, enzymatic activities and cell signaling activation. Under stress, HF(2) diet dramatically decreased the amount of Ca(2+) required to open the mPTP (13%) suggesting an adverse effect on mitochondrial survival. Cinnamon added to the diet corrected this negative effect and resulted in a partial recovery (30%). The effects related to cinnamon addition to the diet could be due to its antioxidant properties or to the observed modulation of PI3K-AKT-GSK3beta and MAPK-P38 pathways or to a combination of both. These data suggest a protective effect of cinnamon on brain mitochondria against the negative impact of an HF(2) diet. Cinnamon could be beneficial to counteract deleterious dietary effects in stressed conditions. PMID- 26878797 TI - NKG2D ligands mediate immunosurveillance of senescent cells. AB - Cellular senescence is a stress response mechanism that limits tumorigenesis and tissue damage. Induction of cellular senescence commonly coincides with an immunogenic phenotype that promotes self-elimination by components of the immune system, thereby facilitating tumor suppression and limiting excess fibrosis during wound repair. The mechanisms by which senescent cells regulate their immune surveillance are not completely understood. Here we show that ligands of an activating Natural Killer (NK) cell receptor (NKG2D), MICA and ULBP2 are consistently up-regulated following induction of replicative senescence, oncogene induced senescence and DNA damage - induced senescence. MICA and ULBP2 proteins are necessary for efficient NK-mediated cytotoxicity towards senescent fibroblasts. The mechanisms regulating the initial expression of NKG2D ligands in senescent cells are dependent on a DNA damage response, whilst continuous expression of these ligands is regulated by the ERK signaling pathway. In liver fibrosis, the accumulation of senescent activated stellate cells is increased in mice lacking NKG2D receptor leading to increased fibrosis. Overall, our results provide new insights into the mechanisms regulating the expression of immune ligands in senescent cells and reveal the importance of NKG2D receptor-ligand interaction in protecting against liver fibrosis. PMID- 26878798 TI - LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development. AB - The secreted leucine-rich glioma inactivated 1 (LGI1) protein is an important actor for human seizures of both genetic and autoimmune etiology: mutations in LGI1 cause inherited temporal lobe epilepsy, while LGI1 is involved in antibody mediated encephalitis. Remarkably, Lgi1-deficient (Lgi1(-/-)) mice recapitulate the epileptic disorder and display early-onset spontaneous seizures. To understand how Lgi1-deficiency leads to seizures during postnatal development, we here investigated the early functional and structural defects occurring before seizure onset in Lgi1(-/-) mice. We found an increased excitatory synaptic transmission in hippocampal slices from Lgi1(-/-) mice. No structural alteration in the morphology of pyramidal cell dendrites and synapses was observed at this stage, indicating that Lgi1-deficiency is unlikely to trigger early developmental abnormalities. Consistent with the presynaptic subcellular localization of the protein, Lgi1-deficiency caused presynaptic defects, with no alteration in postsynaptic AMPA receptor activity in Lgi1-/- pyramidal cells before seizure onset. Presynaptic dysfunction led to increased synaptic glutamate levels, which were associated with hyperexcitable neuronal networks. Altogether, these data show that Lgi1 acts presynaptically as a negative modulator of excitatory synaptic transmission during early postnatal development. We therefore here reveal that increased presynaptic glutamate release is a key early event resulting from Lgi1-deficiency, which likely contributes to epileptogenesis. PMID- 26878799 TI - Iron mitigates DMT1-mediated manganese cytotoxicity via the ASK1-JNK signaling axis: Implications of iron supplementation for manganese toxicity. AB - Manganese (Mn(2+)) neurotoxicity from occupational exposure is well documented to result in a Parkinson-like syndrome. Although the understanding of Mn(2+) cytotoxicity is still incomplete, both Mn(2+) and Fe(2+) can be transported via the divalent metal transporter 1 (DMT1), suggesting that competitive uptake might disrupt Fe(2+) homeostasis. Here, we found that DMT1 overexpression significantly enhanced Mn(2+) cytoplasmic accumulation and JNK phosphorylation, leading to a reduction in cell viability. Although a robust activation of autophagy was observed alongside these changes, it did not trigger autophagic cell death, but was instead shown to be essential for the degradation of ferritin, which normally sequesters labile Fe(2+). Inhibition of ferritin degradation through the neutralization of lysosomal pH resulted in increased ferritin and enhanced cytoplasmic Fe(2+) depletion. Similarly, direct Fe(2+) chelation also resulted in aggravated Mn(2+)-mediated JNK phosphorylation, while Fe(2+) repletion protected cells, and this occurs via the ASK1-thioredoxin pathway. Taken together, our study presents the novel findings that Mn(2+) cytotoxicity involves the depletion of the cytoplasmic Fe(2+) pool, and the increase in autophagy-lysosome activity is important to maintain Fe(2+) homeostasis. Thus, Fe(2+) supplementation could have potential applications in the prevention and treatment of Mn(2+)-mediated toxicity. PMID- 26878800 TI - Production, Characterization, and Epitope Mapping of Monoclonal Antibodies Against Different Subtypes of Rabbit Hemorrhagic Disease Virus (RHDV). AB - In 2010, a new rabbit hemorrhagic disease virus (RHDV) variant, designated RHDV2, was identified for the first time in Italy. Studies have shown that RHDV2 differs from RHDV1 (traditional RHDV) in terms of its antigenic profile and genetic characteristics. The VP60 protein of RHDV is a structural protein that plays important roles in viral replication, assembly, and immunogenicity. In this study, we immunized BALB/c mice with recombinant VP60 proteins from different RHDV subtypes. After three rounds of subcloning, type-specific positive hybridoma clones of RHDV1 and RHDV2 were further identified by an enzyme-linked immunosorbent assay, Western blotting, and an indirect immunofluorescence assay. Finally, three monoclonal antibodies (MAbs) (1D6, 1H2, and 3F2) that only recognize RHDV1, and four MAbs (1G2, 2C1, 3B7, and 5D6) that only recognize RHDV2 were identified. The epitopes recognized by these MAbs were mapped by Western blotting. Sequence analysis showed that the epitope sequences recognized by 1D6, 1H2, and 3F2 are highly conserved (98%) among RHDV1 strains, whereas the epitope sequences recognized by 1G2, 2C1, 3B7, and 5D6 are 100% conserved among RHDV2 strains. The high conservation of the epitope sequence showed that the screened MAbs were type-specific, and that they could distinguish different RHDV subtypes. PMID- 26878801 TI - Are we failing to protect threatened mangroves in the Sundarbans world heritage ecosystem? AB - The Sundarbans, the largest mangrove ecosystem in the world, is under threat from historical and future human exploitation and sea level rise. Limited scientific knowledge on the spatial ecology of the mangroves in this world heritage ecosystem has been a major impediment to conservation efforts. Here, for the first time, we report on habitat suitability analyses and spatial density maps for the four most prominent mangrove species--Heritiera fomes, Excoecaria agallocha, Ceriops decandra and Xylocarpus mekongensis. Globally endangered H. fomes abundances declined as salinity increased. Responses to nutrients, elevation, and stem density varied between species. H. fomes and X. mekongensis preferred upstream habitats. E. agallocha and C. decandra preferred down-stream and mid-stream habitats. Historical harvesting had negative influences on H. fomes, C. decandra and X. mekongensis abundances. The established protected area network does not support the most suitable habitats of these threatened species. We therefore recommend a reconfiguration of the network to include these suitable habitats and ensure their immediate protection. These novel habitat insights and spatial predictions can form the basis for future forest studies and spatial conservation planning, and have implications for more effective conservation of the Sundarbans mangroves and the many other species that rely on them. PMID- 26878802 TI - Prostate cancer: The applicability of textural analysis of MRI for grading. PMID- 26878804 TI - Bladder cancer: Active surveillance for low-grade Ta bladder tumours. PMID- 26878805 TI - Bladder cancer: Urinary microRNA profiling for predicting UCB recurrence. PMID- 26878803 TI - Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. AB - Erectile dysfunction (ED) is a common complication of diabetes, affecting up to 75% of all diabetic men. Although the aetiology of diabetic ED is multifactorial, endothelial dysfunction is recognized as a mainstay in the pathophysiology of the disease. Endothelial dysfunction is induced by the detrimental actions of high glucose levels and increased oxidative stress on endothelial cells that make up the vascular lining. Besides directly injuring the endothelium, diabetes might also hamper vascular repair mechanisms of angiogenesis and vasculogenesis. These states exacerbate and maintain endothelial dysfunction, impairing vasorelaxation events and cavernosal blood perfusion, which are crucial for normal erectile function. PMID- 26878806 TI - Correlation Between Visual Inspection and Ultrasonography to Identify the Distal Branches of the Superficial Peroneal Nerve: A Cadaveric Study. AB - The anatomy of the superficial peroneal nerve (SPN) and, more precisely, of the distal branches of the SPN at the ankle has attracted interest owing to the possibility of injury when performing ankle arthroscopy. The anterolateral portal is one of the most commonly used portals in ankle arthroscopy, and the intermediate dorsal cutaneous nerve can easily be injured during portal placement. The purpose of the present study was to assess whether visual inspection and palpation of the cutaneous nerves at the ankle differed from examination with ultrasonography and whether the 2 examination techniques correlated with the anatomic location of the SPN, which was verified by cadaver dissection. First, visual examination and palpation was performed to identify the SPN, after which 12 cadaver legs from separate specimens were examined with ultrasonography to mark the course of the SPN. We then measured the distance between the nerve as identified with gross visualization/palpation and ultrasound examination, and compared these with the precise location determined by anatomic dissection. The use of ultrasonography to determine the course of the SPN was good or excellent in 11 of the 12 legs (91.7%) studied. In contrast, gross visualization/palpation was good or excellent in 4 legs (33.3%). Excellent agreement was observed between the ultrasound markings and the anatomic dissection results. However, the visual examination poorly identified the course and the anatomic variations of the nerve branches evidenced in the anatomic dissection. From these findings in cadaver specimens, ultrasound identification of the SPN and its branches is likely preferable to gross visualization/palpation before placement of the anterolateral arthroscopic portal to the ankle. PMID- 26878807 TI - A Commentary on the Diagnosis and Treatment of Superficial Peroneal (Fibular) Nerve Injury and Entrapment. PMID- 26878808 TI - Two-Pin Fixation of Proximal Interphalangeal Joint Fusion for Hammertoe Correction. AB - Single-pin external Kirschner wire (K-wire) fixation has traditionally been a mainstay in proximal interphalangeal joint fusion for central hammertoe repair. Concerns over cosmesis, inconvenience, pin tract infection, hardware failure, nonunion, and early hardware removal have led to the development of implantable internal fixation devices. Although numerous implantable devices are now available and represent viable options for hammertoe repair, they are costly and often pose a challenge in the event removal becomes necessary. An alternative fixation option not typically used is a 2-pin K-wire fixation technique. The perceived advantage of obtaining 2 points of fixation compared with 1 across the fusion site is improved stability against the rotational and bending forces, thus decreasing the potential for pin-related complications. A retrospective assessment of 91 consecutive hammertoe repairs consisting of proximal interphalangeal joint fusion with 2-pin fixation in 60 patients was performed. The K-wires were removed at 6 weeks postoperatively, and the overall postoperative follow-up duration was 28.56 (range 1.40 to 86.83) months. Of the 91 digits, 89 (98%) did not encounter a complication postoperatively and 2 (2.20%) had sustained loosened or broken hardware. No postoperative infection was encountered. The low incidence of complications observed supports the 2-pin K wire fixation technique as a low-cost and viable construct for proximal interphalangeal joint fusion hammertoe repair. PMID- 26878810 TI - Structural evolution and mechanical behaviour of Pt nanoparticle superlattices at high pressure. AB - High pressure is an effective means for tuning the interparticle distances of nanoparticle (NP) superlattices and thus for modifying their physical properties and functionalities. In this work, we determined the evolution of inter-NP distances of a Pt NP superlattice with increasing pressure using an in situ synchrotron small-angle X-ray scattering (SAXS) technique in a diamond-anvil cell (DAC). Transmission electron microscopy (TEM) was used to characterize the microstructures of pre- and post-compression samples. Our results demonstrate that the evolution of Pt NP assemblies with increasing pressure consists of four stages: (1) ligand elastic response, (2) uniform compression, (3) ligand detachment from NP surfaces, and (4) deviatoric compression of ligands between neighboring NPs. By controlling the magnitudes of applied pressure and deviatoric stress, one can sinter NPs into novel architectures such as nanowires and nanoceramics. PMID- 26878809 TI - Acute Primary Hematogenous Osteomyelitis in the Epiphysis of the Distal Tibia: A Case Report With Review of the Literature. AB - Osteomyelitis originating in the epiphysis of the long bones is quite rare and is usually found at either the distal femur or the proximal tibia. We report the case of a 12-year-old male with epiphyseal osteomyelitis that had developed in the distal tibia. To the best of our knowledge, this is the first published case report. The patient's history of a trauma that resembled an ankle sprain had delayed the diagnosis and subsequently led him to develop septic arthritis. The ankle is a common site of simple trauma; however, epiphyseal osteomyelitis is rare at this site. Therefore, if the symptoms continue or worsen after trauma, the clinician should check the affected site and take a more aggressive approach to make an early diagnosis. PMID- 26878811 TI - Intramolecular charge transfer in aminobenzonitriles and tetrafluoro counterparts: fluorescence explained by competition between low lying excited states and radiationless deactivation. Part II: influence of substitution on luminescence patterns. AB - In this paper, we study the mechanisms of charge transfer, luminescence and radiationless decay of three derivatives of 4-aminobenzonitrile (ABN): dimethyl ABN (DMABN) and the tetrafluorinated derivatives, ABN-4F and DMABN-4F. Our CASSCF/CASPT2 computations explain the different luminescence patterns observed in these three compounds and in comparison with the parent system, ABN, in spite of their similar architecture. We have found that the modifications made by the different substitutions in ABN tune the relative energies of the locally excited (LE) and charge transfer (CT) excited states due to electronic and structural factors. In all cases, the only potentially emitting species of CT character is the twisted-ICT. The increasing stabilization of this later species in the series formed by ABN-4F, DMABN and DMABN-4F explains the increasing intensity of the anomalous emission band in these compounds. Nevertheless, other factors like probability of emission vs. nonradiative decay must have also been taken into account. In fact fluoro-substitution increases the accessibility to conical intersections of the excited states with the ground state, opening an internal conversion channel that decreases the fluorescence quantum yield in the fluorinated derivatives. Our results also show that the involvement of the pi sigma* state in the CT process is only possible in ABN-4F, but even in this case it is not probable. PMID- 26878812 TI - Erythrocytes and their role as health indicator: Using structure in a patient orientated precision medicine approach. AB - The relevance of erythrocyte light microscopy analysis (a well-known haematological method) is under the spotlight, however there is a place for innovative electron microscopy, (together with biochemical markers) in a pathology laboratory. Inflammation is a key indicator of the health status and erythrocytes are extremely sensitive to oxidative stress or cytokine upregulation, which typically accompany systemic inflammation in most diseases. They are probably the most adaptable cells, and due to their short lifespan, may form a vital indicator of health, and could play a central part in tracking disease and treatment. As the NIH is proposing a precision medicine approach and because individualised medicine should form an essential part in diagnosis and treatment, biophysical combined with biochemical analysis of erythrocytes may be a novel method to track the inflammatory status before and after treatment. This will allow a fully individualised patient orientated precision medicine approach, where one-medication-regime-fits-all is no longer appropriate. PMID- 26878814 TI - The Evans Aldol-Prins cyclization: a general and stereoselective method for the synthesis of 2,3,4,5,6-pentasubstituted tetrahydropyrans. AB - A general and stereoselective method to synthesize 2,3,4,5,6-pentasubstituted tetrahydropyrans in three steps starting from three different aldehydes is described. Key substrates beta,gamma-unsaturated N-acyloxazolidin-2-ones were subjected to an "Evans Aldol-Prins" protocol to generate five sigma-bonds and five stereocenters in only a one-pot process with yields up to 60% and excellent stereoselectivities. PMID- 26878813 TI - Acute Care Pediatric Nurse Practitioner: The 2014 Practice Analysis. AB - INTRODUCTION: Practice research serves as the certification framework for validating advanced practice roles and updating national qualifying examinations. This national study describes the current practice of the acute care pediatric nurse practitioner (AC PNP) to inform an update of the Certified Pediatric Nurse Practitioner-Acute Care (CPNP-AC) examination content outline. METHOD: A descriptive analysis was performed of the responses of 319 pediatric nurse practitioners, practicing in an acute care role, who completed a practice survey in 2014. RESULTS: Respondents were primarily White women with a mean age of 40 years; 75% had been formally educated as AC PNPs, compared with 48% in 2009. Regional practice was most heavily concentrated in the Southeast (28%) and Midwest (27%). Most respondents (81%) practiced in urban areas. Respondents reported spending 75% of practice time in inpatient settings. The most frequently cited areas of practice were critical care (36%), followed by emergency department (9%) and subspecialty practices. DISCUSSION: This third analysis of AC PNP practice 10 years after initiation of the CPNP-AC certification examination demonstrates changes in clinical practice and educational preparation. PMID- 26878817 TI - Contrast-enhanced ultrasound and computerized tomography perfusion imaging of a liver fibrosis-early cirrhosis in dogs. AB - BACKGROUND AND AIM: To assess liver fibrosis stages in a liver fibrosis-early cirrhosis model in dogs, the clinical efficiency of contrast-enhanced ultrasound (CEUS) and computed tomography (CT) perfusion imaging were compared. METHODS: Hepatic vein arriving time (HVAT), hepatic artery arriving time, and hepatic artery to vein transit time (HA-VTT) were measured on CEUS. Total liver perfusion (TLP), portal vein perfusion (PVP), hepatic artery perfusion, and hepatic perfusion index (HPI) were measured on CT perfusion imaging. Histologic examination of liver specimens of the animals was performed to assess the fibrosis stage. RESULTS: For assessment of liver fibrosis, the area under the receiver operating characteristic curve of CEUS indexes HVAT and HA-VTT were 0.865 and 0.930, respectively; the perfusion CT indexes TLP, PVP, and HPI were 0.797, 0.800, and 0.220, respectively; the serological index hyaluronic acid was 0.793. While for assessment of early cirrhosis, the area under the receiver operating characteristic curve of CEUS indexes HVAT and HA-VTT were 0.915 and 0.948, respectively; the perfusion CT indexes TLP, PVP, and HPI were 0.737, 0.765, and 0.218, respectively; the serological index hyaluronic acid was 0.627. CONCLUSIONS: This study showed that both CEUS and CT perfusion imaging have the potential to be complementary imaging tools in the evaluation of liver fibrosis. While CEUS is the better choice and the index HA-VTT can be considered as non invasive semi-quantitative indexes for diagnosing liver fibrosis and early cirrhosis. PMID- 26878818 TI - The 'Leaky Pipeline'. AB - Gender bias is widespread and needs to be acknowledged and addressed by the scientific community. In this Guest Editorial, M. Resmini, Professor of Materials Chemistry at the Queen Mary University of London, describes how supervisors can play an important role in addressing the 'leaky pipeline', namely, the progressive loss of capable women from STEM disciplines. PMID- 26878816 TI - Initial varus displacement of proximal humerus fractures results in similar function but higher complication rates. AB - PURPOSE: To investigate the effect of initial varus or valgus surgical neck alignment on outcomes of patients who sustained proximal humerus fractures treated with open reduction and internal fixation (ORIF). METHODS: An institutional review board approved database of proximal humerus fractures treated with locked plates was reviewed. Of 185 fractures in the database, 101 fractures were identified and met inclusion criteria. Initial varus displacement was seen in 47 fractures (OTA types 11.A2.2, A3.1, A3.3, B1.2, B2.2, C1.2, C2.2, or C2.3) and initial valgus displacement was observed in 54 fractures (OTA types 11.A2.3, B1.1, C1.1, or C2.1). All patients were treated in a similar manner and examined by the treating physician at standard intervals. Functional outcomes were quantified via the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and physical examination data at 12 months. Radiographs were reviewed for complications of healing. Additionally, complication rate and reoperation rate were investigated. RESULTS: Patients who presented with initial varus displacement had an average age of 59.3 years, while patients in the valgus group had an average age of 62.4 years. Overall, there was no statistically significant difference in age, sex distribution, BMI, fracture parts, screws used, or implant plate type between the two groups. At a minimum 12 months follow up, there was no significant difference in DASH scores between those presenting with varus versus valgus fracture patterns. In addition, no significant differences were seen in final shoulder range of motion in any plane. Overall, 30 patients included in this study developed a complication. A significantly greater number of patients in the initial varus cohort developed complications (40.4%), as compared to 20.3% of patients in the initial valgus cohort (P=0.03). Fourteen patients in this study underwent reoperation. Nine of these patients were in the varus cohort, while 5 were in the valgus cohort (P=0.15). CONCLUSIONS: In this study, initial surgical neck displacement in varus or valgus was found to not significantly affect functional outcome. Based upon our findings, patients with varus displaced proximal humerus fractures are at a greater risk of developing postoperative complications than those who present with initial valgus displaced fracture patterns. PMID- 26878815 TI - Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease. AB - OBJECTIVE: The purpose of this study was to investigate whether cerebrospinal fluid (CSF) levels of tau, phosphorylated tau, beta-amyloid42 , alpha-synuclein, neurofilament light, and YKL-40 change over time and if changes correlate with motor progression and/or cognitive decline in patients with PD and controls. METHODS: We included 63 patients with PD (nondemented) and 21 neurologically healthy controls from the prospective and longitudinal Swedish BioFINDER study, all of whom had clinical assessments and lumbar punctures at baseline and after 2 years. RESULTS: CSF tau levels correlated strongly with alpha-synuclein. The levels of CSF alpha-synuclein, tau, phosphorylated tau, neurofilament light, and YKL-40, but not beta-amyloid42 , increased in CSF over 2 years in PD. No changes were seen in the control group. Studying patients with a short disease duration ( <= 5 years) and patients with a long disease duration ( > 5 years) separately, alpha-synuclein and tau only increased in the PD group with long disease duration. In the PD group, an increase in phosphorylated tau over 2 years correlated with faster motor progression and faster cognitive decline. An increase in YKL-40 over 2 years correlated with faster cognitive decline. CONCLUSION: CSF biomarkers reflecting Lewy body pathology and neurodegeneration (alpha-synuclein), neuronal degeneration (tau, phosphorylated tau, and neurofilament light), and inflammation (YKL-40) increase significantly over 2 years in PD. CSF levels of alpha-synuclein and tau correlate and remain stable in the early symptomatic phase of PD but increase in the later phase. We hypothesize that CSF alpha-synuclein levels might increase as a result of more intense neurodegeneration in PD with long disease duration. (c) 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID- 26878819 TI - International Consensus Statement on Allergy and Rhinology: Rhinosinusitis Executive Summary. AB - BACKGROUND: The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). This executive summary consolidates the findings of the ICAR:RS document. METHODS: ICAR:RS presents over 140 topics in the forms of evidence-based reviews with recommendations (EBRRs) and evidence-based reviews (EBR). The structured recommendations of the EBRR sections are summarized in this executive summary. RESULTS: This summary compiles the EBRRs regarding medical and surgical management of acute RS (ARS) and chronic RS with and without nasal polyps (CRSwNP and CRSsNP). CONCLUSION: This ICAR:RS Executive Summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS. PMID- 26878820 TI - Hierarchically structured activated carbon for ultracapacitors. AB - To resolve the pore-associated bottleneck problem observed in the electrode materials used for ultracapacitors, which inhibits the transport of the electrolyte ions, we designed hierarchically structured activated carbon (HAC) by synthesizing a mesoporous silica template/carbon composite and chemically activating it to simultaneously remove the silica template and increase the pore volume. The resulting HAC had a well-designed, unique porous structure, which allowed for large interfaces for efficient electric double-layer formation. Given the unique characteristics of the HAC, we believe that the developed synthesis strategy provides important insights into the design and fabrication of hierarchical carbon nanostructures. The HAC, which had a specific surface area of 1,957 m(2) g(-1), exhibited an extremely high specific capacitance of 157 F g(-1) (95 F cc(-1)), as well as a high rate capability. This indicated that it had superior energy storage capability and was thus suitable for use in advanced ultracapacitors. PMID- 26878822 TI - Palladium-Catalyzed, tert-Butyllithium-Mediated Dimerization of Aryl Halides and Its Application in the Atropselective Total Synthesis of Mastigophorene A. AB - A palladium-catalyzed direct synthesis of symmetric biaryl compounds from aryl halides in the presence of tBuLi is described. In situ lithium-halogen exchange generates the corresponding aryl lithium reagent, which undergoes a homocoupling reaction with a second molecule of the aryl halide in the presence of the palladium catalyst (1 mol %). The reaction takes place at room temperature, is fast (1 h), and affords the corresponding biaryl compounds in good to excellent yields. The application of the method is demonstrated in an efficient asymmetric total synthesis of mastigophorene A. The chiral biaryl axis is constructed with an atropselectivity of 9:1 owing to catalyst-induced remote point-to-axial chirality transfer. PMID- 26878823 TI - Hydride Reduction by a Sodium Hydride-Iodide Composite. AB - Sodium hydride (NaH) is widely used as a Bronsted base in chemical synthesis and reacts with various Bronsted acids, whereas it rarely behaves as a reducing reagent through delivery of the hydride to polar pi electrophiles. This study presents a series of reduction reactions of nitriles, amides, and imines as enabled by NaH in the presence of LiI or NaI. This remarkably simple protocol endows NaH with unprecedented and unique hydride-donor chemical reactivity. PMID- 26878824 TI - A pilot study of traditional indoor biomass cooking and heating in rural Bhutan: gas and particle concentrations and emission rates. AB - Although many studies have reported the health effects of biomass fuels in developing countries, relatively few have quantitatively characterized emissions from biomass stoves during cooking and heating. The aim of this pilot study was to characterize the emission characteristics of different biomass stoves in four rural houses in Bhutan during heating (metal chimney stove), rice cooking (traditional mud stove), fodder preparation (stone tripod stove), and liquor distillation (traditional mud stove). Three stage measurements (before, during, and after the activity had ceased) were conducted for PM2.5 , particle number (PN), CO, and CO2 . When stoves were operated, the pollutant concentrations were significantly elevated above background levels, by an average of 40 and 18 times for PM2.5 and CO, respectively. Emission rates (mg/min) ranged from 1.07 * 102 (PM2.5 ) and 3.50 * 102 (CO) for the stone tripod stove during fodder preparation to 6.20 * 102 (PM2.5 ) and 2.22 * 103 (CO) for the traditional mud stove during liquor distillation. Usable PN data were only available for one house, during heating using a metal chimney stove, which presented an emission rate of 3.24 * 1013 particles/min. Interventions to control household air pollution in Bhutan, in order to reduce the health risks associated with cooking and heating, are recommended. PMID- 26878825 TI - New Perspectives for Old Clusters: Anderson-Evans Anions as Building Blocks of Large Polyoxometalate Frameworks in a Series of Heterometallic 3 d-4 f Species. AB - A series of nine [Sb7W36O133Ln3M2(OAc)(H2O)8](17-) heterometallic anions (Ln3M2; Ln=La-Gd, M=Co; Ln=Ce, M=Ni and Zn) have been obtained by reacting 3 d metal disubstituted Krebs-type tungstoantimonates(III) with early lanthanides. Their unique tetrameric structure contains a novel {MW9O33} capping unit formed by a planar {MW6O24} fragment to which three {WO2} groups are condensed to form a tungstate skeleton identical to that of a hypothetical trilacunary derivative of the E-Keggin cluster. It is shown, for the first time, that classical Anderson Evans {MW6O24} anions can act as building blocks to construct purely inorganic large frameworks. Unprecedented reactivity in the outer ring of these disk-shaped species is also revealed. The Ln3M2 anions possess chirality owing to a {Sb4O4} cluster being encapsulated in left- or right-handed orientations. Their ability to self-associate in blackberry-type vesicles in solution has been assessed for the Ce3Co2 derivative. PMID- 26878826 TI - Efficacy of an ethanol/guar/triclosan/glycerine gel on bacteria and yeast loads in canine pododermatitis: a pilot study. AB - OBJECTIVES: To assess efficacy of a gel compound containing guar, glycerine, triclosan and ethanol (Pawcare(r), JOKER Technologies, Kerzers, Switzerland) in decreasing bacterial and yeast loads on the paws of dogs with erythematous, greasy and/or malodorous pododermatitis. METHODS: In 20 dogs, each with at least two affected paws, semiquantitative Malassezia species counts were performed on 10 oil-immersion fields (range: 0 to 30) from acetate tapes pressed on the palmar/plantar surface of one paw. Half of the area was sampled before and the other half immediately after the application of Pawcare((r)) . With a similar procedure, swab samples were collected from the other paw for bacterial culture, identification and evaluation of colony-forming units before and immediately after treatment. Statistical evaluation of pre- and posttreatment counts was performed with the Wilcoxon signed-rank test. RESULTS: Nine dogs were positive for Malassezia species Mean acetate tape preparation counts decreased significantly from 8.78 (+/-8.03) to 5.668 (+/-6.65) (P=0.0039) after treatment. Twenty-five bacterial isolates of 11 different species were cultured in 19 dogs. Posttreatment cultures were sterile in 8 dogs that had an initial zero or low number (1 to 2 log counts) of colony-forming units. In cases with a higher pre treatment number of colony forming units (2 to 6 log counts), there was a significant decrease - by a mean of 1.16 log counts (pre 3.12 +/-1.69, post 1.96 +/-1.57) (P=0.0002). CLINICAL SIGNIFICANCE: The findings of the present study support the use of PawCare(r) gel to decrease bacterial and yeast loads in dogs affected by chronic diseases involving the inter-digital spaces. PMID- 26878828 TI - Safety, tolerability, and outcomes of regular automated red cell exchange transfusion in the management of sickle cell disease. AB - We report here our experience with regular automated red cell exchange transfusion for the management of chronic complications of sickle cell disease in 50 patients in our institution from June 2011 to December 2014. The mean sickle hemoglobin level was 44% and 8.5% pre- and post-transfusion, respectively. Platelets were reduced by a mean 70% during the procedure with a count of less than 50 * 109 /l in 6% of cases. The alloimmunization rate was 0.065/100 units of red cells with no hemolytic reactions. Patients with no iron overload at baseline showed no evidence of iron accumulation with a mean liver iron concentration of 1.6 mg/g dry tissue and 1.9 mg/g dry tissue at baseline and 36 months, respectively. All six patients with pre-existing iron overload and on chelation therapy, showed a gradual reduction of their liver iron concentration and two patients could discontinue chelation during the follow-up period. Seventy percentage of patients who were on the programme for recurrent painful crises showed a sustained reduction in the number of emergency hospital attendances; the mean number of days in hospital for emergency treatment was 103 in the year prior to commencing ARCET and reduced to 62 (40%) after the first 12 months, 51 (50%) after 24 months, and 35 days (66%) after 36 months. J. Clin. Apheresis 31:545 550, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26878827 TI - Nalbuphine and butorphanol reverse opioid-induced respiratory depression but increase arousal in etorphine-immobilized goats (Capra hircus). AB - OBJECTIVES: To evaluate and compare the efficacy of two opioid agonist antagonists, nalbuphine and butorphanol, in reversing etorphine-induced respiratory depression in immobilized goats. STUDY DESIGN: Prospective, crossover, experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus). METHODS: Eight minutes following immobilization with an intramuscular injection of 0.1 mg kg(-1) etorphine, goats were given one of nalbuphine (0.8 mg kg(-1) ), butorphanol (0.1 mg kg(-1) ) or sterile water intravenously, in random order in three trials. Respiratory rate (fR ), ventilation, tidal volume, oxygen consumption (VO2 ) and carbon dioxide production (VCO2 ) were measured continuously. Arterial blood samples to determine PaO2 and PaCO2 were taken 2 minutes before and at 5 minute intervals after etorphine administration for 25 minutes. RESULTS: Both nalbuphine and butorphanol increased mean PaO2 from 44 mmHg (5.9 kPa) to 63 mmHg (8.4 kPa) after etorphine administration. Butorphanol, but not nalbuphine, also corrected hypopnea and hypoventilation such that fR increased from 13 +/- 4 to 21 +/- 7 breaths minute(-1) (compared with 16 +/- 6 breaths minute(-1) following nalbuphine) and ventilation increased from 4.69 +/- 3.04 to 6.91 +/- 4.42 L minute(-1) following butorphanol administration. Despite decreases in PaCO2 following nalbuphine and butorphanol, PaCO2 remained elevated compared with pre immobilization values [nalbuphine: 34 +/- 3 mmHg (4.5 +/- 0.3 kPa); butorphanol: 34 +/- 2 mmHg (4.5 +/- 0.3 kPa)] throughout the immobilization. Both agents also decreased the level of immobilization, and increased VO2 and VCO2 . CONCLUSIONS: Nalbuphine and butorphanol significantly improved respiratory function in immobilized goats, with butorphanol eliciting a greater positive response than nalbuphine. However, both opioid agonist-antagonists partly reversed etorphine induced immobilization. CLINICAL RELEVANCE: Butorphanol and nalbuphine can be used to improve respiratory parameters in etorphine-immobilized wildlife, with butorphanol being more effective, but unwanted arousal can occur. PMID- 26878829 TI - Imperfection works: Survival, transmission and persistence in the system of Heliothis virescens ascovirus 3h (HvAV-3h), Microplitis similis and Spodoptera exigua. AB - Ascoviruses are insect-specific large DNA viruses that mainly infect noctuid larvae, and are transmitted by parasitoids in the fields. Heliothis virescens ascovirus 3h (HvAV-3h) has been recently isolated from Spodoptera exigua, without parasitoid vector identified previously. Here we report that Microplitis similis, a solitary endoparasitoid wasp, could transmit HvAV-3h between S. exigua larvae in the laboratory. When the female parasitoid wasp acquired the virus and served as a vector, the period of virion viability on the ovipositor was 4.1 +/- 1.4 days. Infected host larvae were still acceptable for egg laying by parasitoids, and the parasitoids thereafter transmitted virus to healthy hosts. Virus acquisition occurred only from donor hosts between 3 and 9 days post infection. The peak of virus acquisition (80.9 +/- 6.3%) was found when M. similis wasps oviposited in larvae that had been inoculated with the virus 7 days previously. When virus infection of the host took place during the life cycle of the parasitoid wasp, it caused 1- to 4-day-old immature parasitoids death in the host, whilst a small proportion of 5- to 6-day-old and the majority of 7-day-old parasitoids larvae survived from the virus-infected hosts. Viral contamination did not reduce the life span or fecundity of female M. similis. PMID- 26878830 TI - Modulatory effects of the basolateral amygdala alpha2-adrenoceptors on nicotine induced anxiogenic-like behaviours of rats in the elevated plus maze. AB - The present study was designed to clarify whether alpha2-adrenoceptors of the basolateral amygdala (BLA) are involved in nicotine-induced anxiogenic-like behaviours. Adult male Wistar rats were bilaterally cannulated in the BLA and anxiety-like behaviours were assessed in an elevated plus maze (EPM) task. Systemic intraperitoneal (i.p.) administration of nicotine (0.3, 0.5 and 0.7 mg/kg) dose-dependently decreased open arm time (%OAT) and open arm entry (%OAE), indicating the anxiogenic-like effect of nicotine. The activation of the BLA alpha2-adrenoceptors by the injection of alpha2-receptor agonist, clonidine (0.1, 0.3 and 0.5 MUg/rat) into the BLA (intra-BLA) reversed nicotine-induced anxiogenic-like behaviours. It is important to note that intra-BLA injection of a higher dose of clonidine (0.5 MUg/rat) by itself increased %OAT, but not %OAE which showed an anxiolytic effect of the agonist. On the other hand, intra-BLA injection of different doses of alpha2-adrenoceptor antagonist, yohimbine (1, 3 and 5 MUg/rat) in combination with an ineffective dose of nicotine (0.3 mg/kg) decreased %OAT and %OAE, suggesting a potentiative effect of the antagonist on nicotine response. In addition, intra-BLA injection of the same doses of yohimbine did not alter %OAT and %OAE. Interestingly, intra-BLA injection of yohimbine (0.5 and 1 MUg/rat) significantly reversed the inhibitory effect of clonidine on nicotine-induced anxiogenic-like behaviours. It should be considered that the drug treatments had no effect on locomotor activity in all experiments. Taken together, it can be concluded that nicotine produces anxiogenic-like behaviours which may be mediated through the BLA alpha2-adrenoceptor mechanism. PMID- 26878831 TI - Strong pollinator-mediated selection for increased flower brightness and contrast in a deceptive orchid. AB - Contrasting flower color patterns that putatively attract or direct pollinators toward a reward are common among angiosperms. In the deceptive orchid Anacamptis morio, the lower petal, which makes up most of the floral display, has a light central patch with dark markings. Within populations, there is pronounced variation in petal brightness, patch size, amount of dark markings, and contrast between patch and petal margin. We tested whether pollinators mediate selection on these color traits and on morphology (plant height, number of flowers, corolla size, spur length), and whether selection is consistent with facilitated or negative frequency-dependent pollination. Pollinators mediated strong selection for increased petal brightness (Deltabetapoll = 0.42) and contrast (Deltabetapoll = 0.51). Pollinators also tended to mediate stabilizing selection on brightness (Deltagammapoll = -0.27, n.s.) favoring the most common phenotype in the population. Selection for reduced petal brightness among hand-pollinated plants indicated a fitness cost associated with brightness. The results demonstrate that flower color traits influence pollination success and seed production in A. morio, indicating that they affect attractiveness to pollinators, efficiency of pollen transfer, or both. The documented selection is consistent with facilitated pollination and selection for color convergence toward cooccurring rewarding species. PMID- 26878832 TI - Glandular epithelial abnormalities on thinprep(r) pap tests: Clinical and cytohistologic correlation. AB - BACKGROUND: Although the incidence of glandular epithelial abnormalities on cervical cytology is low, the clinical and histologic findings are often significant. The laboratory's 12-year experience is reported. METHODS: from January 1, 2003 to December 31, 2014, the Cytopathology Laboratory of the University of Wisconsin Hospital and Clinics processed 191,087 ThinPrep((r)) Pap Tests of which 184 (0.1%) were reported as glandular epithelial abnormalities. One hundred forty-three (78%) of these cases had histologic follow-up and form the basis of this study. Of the 143 women (mean age, 52; median, 50), 45% presented with vaginal bleeding and 55% were asymptomatic. The cytologic groups included atypical glandular cells, atypical glandular cells; favor a neoplastic process, atypical endocervical cells, atypical endocervical cells; favor a neoplastic process, endocervical adenocarcinoma in situ, atypical endometrial cells and adenocarcinoma, NOS. RESULTS: Overall, the histologic follow-up showed epithelial abnormalities including endometrial and endocervical carcinoma, endocervical adenocarcinoma in situ, CIN 3 involving endocervical glands and metastatic carcinoma in 78% of the cases. The diagnoses were age-dependent and influenced by clinical symptomatology. CONCLUSION: Glandular epithelial abnormalities on Pap tests warrant further clinical investigation. PMID- 26878833 TI - Spectroscopic Characterization and Reactivity of Triplet and Quintet Iron(IV) Oxo Complexes in the Gas Phase. AB - Closely structurally related triplet and quintet iron(IV) oxo complexes with a tetradentate aminopyridine ligand were generated in the gas phase, spectroscopically characterized, and their reactivities in hydrogen-transfer and oxygen-transfer reactions were compared. The spin states were unambiguously assigned based on helium tagging infrared photodissociation (IRPD) spectra of the mass-selected iron complexes. It is shown that the stretching vibrations of the nitrate counterion can be used as a spectral marker of the central iron spin state. PMID- 26878834 TI - The psychometric testing of the Nursing Teamwork Survey in Iceland. AB - The purpose of this study was to test the psychometric properties of the Nursing Teamwork Survey-Icelandic (NTS-Icelandic), which was translated from US English to Icelandic. The Nursing Teamwork Survey, with 33 items, measures overall teamwork and five factors of teamwork: trust, team orientation, backup, shared mental models, and team leadership. The psychometric testing of the NTS-Icelandic was carried out on data from a pilot study and a national study. The sample for a pilot study included 123 nursing staff from five units, and the sample for a national study included 925 nursing staff from 27 inpatient units. The overall test-retest intraclass correlation coefficient in the pilot study was 0.693 (lower bound = 0.498, upper bound = 0.821) (p < 0.001). The Cronbach's alpha reliability for the total scale and subscales ranged from 0.737 to 0.911. A confirmatory factor analysis indicated a good fit of the data from the national study with the five-factor model for nursing teamwork. The NTS-Icelandic tested valid and reliable in this study. Study findings support further use of the Nursing Teamwork Survey internationally. PMID- 26878835 TI - The effects of cannabis intoxication on motor vehicle collision revisited and revised. AB - AIMS: To determine whether and to what extent acute cannabis intoxication increases motor vehicle crash risk. DESIGN: Study 1 replicates two published meta analyses, correcting for methodological shortcomings. Study 2 is an updated meta analysis using 28 estimates from 21 observational studies. These included studies from three earlier reviews, supplemented by results from a structured search in Web of Science and Google Scholar, and by the personal libraries of the research team. Risk estimates were combined using random-effects models and meta regression techniques. SETTING: Study 1 replicates the analysis of Asbridge et al., based on nine studies from five countries, published 1982-2007; and Li et al., based on nine studies from six countries, published 2001-10. Study 2 involves studies from 13 countries published in the period 1982-2015. PARTICIPANTS: In study 1, total counts extracted totalled 50 877 (27 967 cases, 22 910 controls) for Asbridge et al. and 93 229 (4236 cases and 88 993 controls) for Li et al. Study 2 used confounder-adjusted estimates where available (combined sample size of 222 511) and crude counts from the remainder (17 228 total counts), giving a combined sample count of 239 739. MEASUREMENTS: Odds ratios (OR) were used from case-control studies and adjusted OR analogues from culpability studies. The impact of the substantial variation in confounder adjustment was explored in subsample analyses. FINDINGS: Study 1 substantially revises previous risk estimates downwards, with both the originally reported point estimates lying outside the revised confidence interval. Revised estimates were similar to those of study 2, which found cannabis-impaired driving associated with a statistically significant risk increase of low-to-moderate magnitude [random-effects model OR 1.36 (1.15-1.61), meta-regression OR 1.22 (1.1 1.36)]. Subsample analyses found higher OR estimates for case-control studies, low study quality, limited control of confounders, medium-quality use data and not controlling for alcohol intoxication. CONCLUSIONS: Acute cannabis intoxication is associated with a statistically significant increase in motor vehicle crash risk. The increase is of low to medium magnitude. Remaining selection effects in the studies used may limit causal interpretation of the pooled estimates. PMID- 26878836 TI - Reducing the Cost and Preserving the Reactivity in Noble-Metal-Based Catalysts: Oxidation of CO by Pt and Al-Pt Alloy Clusters Supported on Graphene. AB - The oxidation mechanisms of CO to CO2 on graphene-supported Pt and Pt-Al alloy clusters are elucidated by reactive dynamical simulations. The general mechanism evidenced is a Langmuir-Hinshelwood (LH) pathway in which O2 is adsorbed on the cluster prior to the CO oxidation. The adsorbed O2 dissociates into two atomic oxygen atoms thus promoting the CO oxidation. Auxiliary simulations on alloy clusters in which other metals (Al, Co, Cr, Cu, Fe, Ni) replace a Pt atom have pointed to the aluminum doped cluster as a special case. In the nanoalloy, the reaction mechanism for CO oxidation is still a LH pathway with an activation barrier sufficiently low to be overcome at room temperature, thus preserving the catalyst efficiency. This provides a generalizable strategy for the design of efficient, yet sustainable, Pt-based catalysts at reduced cost. PMID- 26878837 TI - Molecular Orbital Controlling Donor Moiety for High-Efficiency Thermally Activated Delayed Fluorescent Emitters. AB - A new donor moiety, 7,7,13,13-tetramethyl-7,13-dihydro-5H-indeno[1,2-b]acridine (IAc), was developed to control the highest occupied molecular orbital (HOMO) dispersion of thermally activated delayed fluorescent (TADF) emitters. The IAc unit expanded the HOMO dispersion of the emitters and increased the quantum efficiency of the TADF devices up to 20.9 %. PMID- 26878838 TI - A three-year follow-up of a nurse-led multidisciplinary pulmonary rehabilitation programme in primary health care: a quasi-experimental study. AB - AIMS AND OBJECTIVES: To investigate the effects of a nurse-led multidisciplinary pulmonary rehabilitation programme conducted in primary health care on functional capacity, quality of life and exacerbation frequency over three years among patients with Chronic Obstructive Pulmonary Disease. BACKGROUND: Although Chronic Obstructive Pulmonary Disease is a chronic respiratory disease, it has been established that pulmonary rehabilitation has positive effects on patients' everyday functioning. However, the duration of these functional improvements, especially when the rehabilitation programmes are provided in primary health care settings, remains to be established. DESIGN: A quasi-experimental design. METHOD: Primary health care patients with Chronic Obstructive Pulmonary Disease (GOLD stages II and III) were included; 49 in the intervention group and 54 in the control group. The intervention comprised a six-week pulmonary rehabilitation programme. Functional capacity was assessed using a six-minute walking test and quality of life by the Clinical COPD Questionnaire at baseline, after one year and three years. Exacerbation frequency was calculated from one year before to three years after the programme. RESULTS: No significant differences between the groups were observed in the six-minute walking-test or the Clinical COPD Questionnaire after one year and three years. On average, there were significant improvements in the six-minute walking-test and the Clinical COPD Questionnaire from baseline to the one-year follow-up. Exacerbation frequency tended to decrease in the intervention group and increase in the control group (interaction test was p = 0.091) but increased again in both groups after three years. CONCLUSION: There was no evidence of the benefit of the nurse-led multidisciplinary pulmonary rehabilitation programme, although the exacerbation frequency tended to decrease in the intervention group after one year. There is a need for support and coaching at regular follow-ups in primary health care. RELEVANCE TO CLINICAL PRACTICE: There is a need to support and coach patients with Chronic Obstructive Pulmonary Disease in primary health care by means of regular follow-ups. PMID- 26878839 TI - Response to Association Between Preinfarction Angina and Angiographic Findings in Non-ST-Segment Elevation Myocardial Infarction. PMID- 26878840 TI - Diagnostic and therapeutic features associated with modification of quality-of life's outcomes between one and six months after major surgery for head and neck cancer. AB - INTRODUCTION: Treatments used in head and neck cancer greatly impact the physical, psychological and functional state of patients. Evaluation of quality of life has become an integral part of the treatment. OBJECTIVE: This retrospective study evaluates features involved in changes in quality of life after major surgery for head and neck cancer within six months, according to self reported outcomes. METHODS: One hundred and thirty patients completed the University of Washington Quality of Life questionnaire one and six months after major surgery for head and neck cancer. A multivariate model was used to evaluate which diagnostic and therapeutic features were related to improvement of quality of life within a six-month period. RESULTS: Significant improvement in most features related to quality of life was already recognizable at six months. Patients submitted to more invasive treatment had the biggest improvement in quality of life between time-points, as well as those patients with bigger tumors. CONCLUSION: After major surgery, patients may undergo fast recovery, with overall quality of life likely to improve in the short-term. Clinicians must be aware of the importance of dealing with treatment-related issues immediately after surgery, with hopeful possibility of on-the-upgrade results. PMID- 26878841 TI - A newly discovered flavivirus in the yellow fever virus group displays restricted replication in vertebrates. AB - A novel flavivirus, provisionally named Bamaga virus (BgV), was isolated from Culex annulirostris mosquitoes collected from northern Australia. Phylogenetic analysis of the complete nucleotide sequence of the BgV genome revealed it clustered with the yellow fever virus (YFV) group, and was most closely related to Edge Hill virus (EHV), another Australian flavivirus, with 61.9% nucleotide and 63.7% amino acid sequence identity. Antigenic analysis of the envelope and pre-membrane proteins of BgV further revealed epitopes common to EHV, dengue and other mosquito-borne flaviviruses. However, in contrast to these viruses, BgV displayed restricted growth in a range of vertebrate cell lines with no or relatively slow replication in inoculated cultures. There was also restricted BgV replication in virus-challenged mice. Our results indicate that BgV is an evolutionary divergent member of the YFV group of flaviviruses, and represents a novel system to study mechanisms of virus host-restriction and transmission. PMID- 26878842 TI - Why did the authors perform a meta-analysis of studies with primary endpoints they consider clinically unimportant? PMID- 26878843 TI - Role of a common variant of Fat Mass and Obesity associated (FTO) gene in obesity and coronary artery disease in subjects from Punjab, Pakistan: a case control study. AB - BACKGROUND: The FTO gene has recently become one of the most extensively investigated genes associated with body mass and has been shown to play a role in cardiovascular diseases as well. The aim of the current study was to investigate the effect of a common variant of FTO gene, rs9939609 in obese and coronary heart disease (CHD) patients of Pakistan and investigate whether it has any influence on the serum biochemical parameters. METHODS: A total of 970 samples (295 obese, 425 CHD and 250 controls) were genotyped using TaqMan allelic discrimination assay. Serum total cholesterol, HDL-C and triglycerides were measured using spectrophotometric methods. LDL-C was calculated by Friedwalds equation. Statistical analysis was done by SPSS version 22. RESULTS: Results showed moderately high minor allele frequency (MAF) in obese and CHD cases as compared to controls (obese = 0.381 CAD = 0.361 and controls = 0.286). The variant was significantly associated with obesity and CAD (obesity odds ratio (OR) = 1.54, confidence interval (CI) = 1.07-2.21, p = 0.0009; CHD OR = 1.43, CI = 1.02-2.01, p = 0.004) in Pakistan. The risk allele did not show a significant association with any of the lipid trait tested (p > 0.05) but a strong association was observed with plasma glucose levels (obese p = 0.001, CAD p = 0.014, controls p = 0.019). CONCLUSION: In conclusion, the variant was associated with obesity and CAD in the studied subjects and its possible effect may involve the blood sugar metabolism but not serum lipid chemistry. PMID- 26878845 TI - The efficacy of topical tranexamic acid in total hip arthroplasty: a meta analysis. AB - BACKGROUND: Topical tranexamic acid (TXA) has been shown to be effective in reducing blood loss and the need for transfusion after total knee arthroplasty. However, the effectiveness of topical TXA use in total hip arthroplasty (THA) still remains unclear. The purpose of this meta-analysis is to examine the safety and efficacy of topical use of TXA following THA. HYPOTHESIS: Topical TXA reduces blood loss and transfusion rates without increasing risk of deep vein thrombosis in patients with THA. METHODS: An electronic literature search of PubMed, Embase, the Cochrane Library, Web of Science and Chinese Biomedical Database was performed, to identify studies published before February 2015. All randomized controlled trials and cohort studies evaluating the efficacy of topical TXA during THA were included. Two independent authors identified the eligible studies, assessed their methodological quality, and extracted data. The data were using fixed-effects or random-effects models with (standard) mean differences and risk ratios for continuous and dichotomous variables, respectively. Data were analysed using RevMan 5.3 software. RESULTS: Fourteen studies encompassing 2594 patients met the inclusion criteria for our meta-analysis. Our meta-analysis indicated that when compared with the placebo group, topical use of TXA significantly reduced total blood loss (MD = -297.65 ml, 95 % CI -371.68 ml, 116.08 ml; P < 0.01), drainage loss (MD = -164.68 ml, 95 % CI -236.63 ml, -92.73 ml; P < 0.01), transfusion rate (RR = 0.26, 95 % CI 0.17, 0.40; P < 0.01) and with less of a drop in haemoglobin level (SMD = -0.66, 95 % CI -0.91, -0.41; P < 0.01) after primary THA. No significant difference in length of hospital stay (MD = -0.40, 95 % CI -0.91, 0.11; P = 0.14), deep vein thrombosis (RR = 1.19, 95 % CI 0.40, 3.57; P = 0.16) and pulmonary embolism (RR = 1.11, 95 % CI 0.11, 10.81; P = 0.21) among the study groups. CONCLUSIONS: Topical TXA could significantly reduce total blood loss, drainage loss, transfusion rates and decrease haemoglobin level following THA, without increasing risk of venous thromboembolisms. PMID- 26878846 TI - The mechanism of high contents of oil and oleic acid revealed by transcriptomic and lipidomic analysis during embryogenesis in Carya cathayensis Sarg. AB - BACKGROUND: Hickory (Carya cathayensis Sarg.) accumulates more than 70% oil and 90% unsaturated fatty acids with considerably high oleic acid in its mature embryo. The concurrent global trancriptomic and lipidomic analyses provided a framework for better understanding of glycerolipid biosynthesis and metabolism in the hickory nut. RESULTS: The synthetical regulation of numerous leading lipid related genes harmonized with the oil accumulation and fatty acid conversion in embryo development. The high level of ACCase correlated positively with fatty acids de novo synthesis, and the synergy of DGAT2 and PDAT promoted the TAG assembly, and oleosins, caleosins and steroleosins were transcribed considerably high for timely energy reserve in oil body. Glycolysis possibly provided sufficient precursors and energy for lipid synthesis. The perfect harmonization of the high level of SAD with low level of FAD2 facilitated the oleic acid accumulation. And the ratio of FATA/FATB or SAD/FATB was proposed for determining the saturated degree of oil. The gene multi-copy event was generated probably for accommodating various survival environments. A thermotolerant defense system including TAG hydrolysis determinants, heat shock proteins, and high ratio of MUFA to PUFA constrained the lipid degradation and provided a guarantee for high lipid content. A batch of potential genes recruited from the co-expression network helps us to understand the lipid synthesis and the response to high temperature better. CONCLUSIONS: The high transcriptional levels of key genes in lipid synthesis promoted the oil accumulation, and the harmonious expression of key ones for unsaturated fatty acids led oleic acid to high levels. PMID- 26878847 TI - Detection of pup odors by non-canonical adult vomeronasal neurons expressing an odorant receptor gene is influenced by sex and parenting status. AB - BACKGROUND: Olfaction is a fundamental sense through which most animals perceive the external world. The olfactory system detects odors via specialized sensory organs such as the main olfactory epithelium and the vomeronasal organ. Sensory neurons in these organs use G-protein coupled receptors to detect chemosensory stimuli. The odorant receptor (OR) family is expressed in sensory neurons of the main olfactory epithelium, while the adult vomeronasal organ is thought to express other types of receptors. RESULTS: Here, we describe Olfr692, a member of the OR gene family identified by next-generation RNA sequencing, which is highly upregulated and non-canonically expressed in the vomeronasal organ. We show that neurons expressing this gene are activated by odors emanating from pups. Surprisingly, activity in Olfr692-positive cells is sexually dimorphic, being very low in females. Our results also show that juvenile odors activate a large number of Olfr692 vomeronasal neurons in virgin males, which is correlated with the display of infanticide behavior. . In contrast, activity substantially decreases in parenting males (fathers), where infanticidal aggressive behavior is not frequently observed. CONCLUSIONS: Our results describe, for the first time, a sensory neural population with a specific molecular identity involved in the detection of pup odors. Moreover, it is one of the first reports of a group of sensory neurons the activity of which is sexually dimorphic and depends on social status. Our data suggest that the Olfr692 population is involved in mediating pup oriented behaviors in mice. PMID- 26878848 TI - Region-specific role of growth differentiation factor-5 in the establishment of sympathetic innervation. AB - BACKGROUND: Nerve growth factor (NGF) is the prototypical target-derived neurotrophic factor required for sympathetic neuron survival and for the growth and ramification of sympathetic axons within most but not all sympathetic targets. This implies the operation of additional target-derived factors for regulating terminal sympathetic axon growth and branching. RESULTS: Here report that growth differentiation factor 5 (GDF5), a widely expressed member of the transforming growth factor beta (TGFbeta) superfamily required for limb development, promoted axon growth from mouse superior cervical ganglion (SCG) neurons independently of NGF and enhanced axon growth in combination with NGF. GDF5 had no effect on neuronal survival and influenced axon growth during a narrow window of postnatal development when sympathetic axons are ramifying extensively in their targets in vivo. SCG neurons expressed all receptors capable of participating in GDF5 signaling at this stage of development. Using compartment cultures, we demonstrated that GDF5 exerted its growth promoting effect by acting directly on axons and by initiating retrograde canonical Smad signalling to the nucleus. GDF5 is synthesized in sympathetic targets, and examination of several anatomically circumscribed tissues in Gdf5 null mice revealed regional deficits in sympathetic innervation. There was a marked, highly significant reduction in the sympathetic innervation density of the iris, a smaller though significant reduction in the trachea, but no reduction in the submandibular salivary gland. There was no reduction in the number of neurons in the SCG. CONCLUSIONS: These findings show that GDF5 is a novel target-derived factor that promotes sympathetic axon growth and branching and makes a distinctive regional contribution to the establishment of sympathetic innervation, but unlike NGF, plays no role in regulating sympathetic neuron survival. PMID- 26878850 TI - Correlation of alpha angle between various radiographic projections and radial magnetic resonance imaging for cam deformity in femoral head-neck junction. AB - PURPOSE: Radial magnetic resonance imaging (MRI) along the axis of the femoral head neck is the gold standard for detection of cam deformity of the proximal femur. This study was performed to identify which plain radiographic projection was best correlated with radial MRI. METHODS: Five different plain radiographic projections and 18 slices of radial MRI were applied to 35 consecutive hips with groin pain and positive impingement sign. Alpha angles were measured to detect the asphericity of the femoral head-neck junction in all images. Radiographs were taken in anteroposterior pelvis, cross-table lateral, 90 degrees Dunn, 45 degrees Dunn and modified 45 degrees Dunn views. Pearson's correlation coefficients were determined to assess the association between the alpha angle obtained from radial MRI and each radiographic technique. The sensitivity, specificity, positive and positive predictive values and accuracy of plain radiographic alpha angle measurements were assessed using a threshold alpha angle value of 50.5 degrees for cam deformity. RESULTS: Pearson's correlation coefficients in the alpha angle values between MRI and plain radiographic projections were 0.45, 0.70, 0.62, 0.81 and 0.69 for the anteroposterior pelvis, cross-table lateral, 90 degrees Dunn, 45 degrees Dunn and modified 45 degrees Dunn views, respectively. In terms of sensitivity and accuracy, the 45 degrees Dunn view had the greatest values. CONCLUSIONS: Alpha angle of the 45 degrees Dunn view was best correlated with that of radial MRI. The 45 degrees Dunn view had better sensitivity and accuracy than other radiographic projections. The 45 degrees Dunn view may be preferable for screening of cam deformity. LEVEL OF EVIDENCE: II. PMID- 26878849 TI - Resveratrol Protects against Titanium Particle-Induced Aseptic Loosening Through Reduction of Oxidative Stress and Inactivation of NF-kappaB. AB - Aseptic implant loosening is closely associated with chronic inflammation induced by implant wear debris, and reactive oxygen species (ROS) play an important role in this process. Resveratrol, a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against wear particle-induced oxidative stress remain unknown. In this study, we evaluated resveratrol's protective effects against wear particle induced oxidative stress in RAW 264.7 macrophages. At non-toxic concentrations, resveratrol showed dose-dependent inhibition of nitric oxide (NO) production, ROS generation, and lipid peroxidation. It also downregulated the gene expression of oxidative enzymes, including inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-1 and NOX-2, and promoted the gene expression and activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx). This protective effect against wear particle induced oxidative stress was accompanied by a reduction of gene expression and release of tumor necrosis factor-alpha (TNF-alpha), and decreased gene expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB). These findings demonstrate that resveratrol can inhibit wear particle-induced oxidative stress in macrophages, and may exert its antioxidant effect and protect against aseptic implant loosening. PMID- 26878851 TI - Biomechanical stability of tape augmentation for anterior talofibular ligament (ATFL) repair compared to the native ATFL. AB - PURPOSE: Current methods of anterior talofibular ligament (ATFL) reconstruction fail to restore the stability of the native ATFL. Therefore, augmented anatomic ATFL reconstruction gained popularity in patients with attenuated tissue and additional stress on the lateral ankle ligament complex. The aim of the present study was to evaluate the biomechanical stability of the InternalBrace (Arthrex Inc., Naples, FL, USA), a tape augmentation designed to augment the traditional Brostrom procedure. METHODS: Twelve (12) fresh-frozen human anatomic lower leg specimens were randomized into two groups: a native ATFL (ATFL) and a tape augmentation group (IB). Dual-energy X-ray absorptiometry (DEXA) scans were carried out to determine bone mineral density (BMD) of the specimens. The ligaments were stressed by internally rotating the tibia against the inverted fixated hindfoot. Torque at failure (Nm) and angle at failure ( degrees ) were recorded. RESULTS: The ATFL group failed at an angle of 33 +/- 10 degrees . In the IB group, construct failure occurred at an angle of 46 +/- 16 degrees . Failure torque reached 8.3 +/- 4.5 Nm in the ATFL group, whereas the IB group achieved 11.2 +/- 7.1 Nm. There was no correlation between angle at ATFL or IB construct failure or torque at failure, respectively, and BMD for both groups. CONCLUSION: This study reveals that tape augmentation for ATFL reconstruction shows similar biomechanical stability compared to an intact native ATFL in terms of torque at failure and angle at failure. BMD did not influence the construct stability. Tape augmentation proved an enhanced initial stability in ATFL reconstruction which may allow for an accelerated rehabilitation process. LEVEL OF EVIDENCE: II. PMID- 26878852 TI - Complete 1H, 15N and 13C assignment of trappin-2 and 1H assignment of its two domains, elafin and cementoin. AB - Trappin-2 is a serine protease inhibitor with a very narrow inhibitory spectrum and has significant anti-microbial activities. It is a 10 kDa cationic protein composed of two distinct domains. The N-terminal domain (38 residues) named cementoin is known to be intrinsically disordered when it is not linked to the elafin. The C-terminal domain (57 residues), corresponding to elafin, is a cysteine-rich domain stabilized by four disulfide bridges and is characterized by a flat core and a flexible N-terminal part. To our knowledge, there is no structural data available on trappin-2. We report here the complete (1)H, (15)N and (13)C resonance assignment of the recombinant trappin-2 and the (1)H assignments of cementoin and elafin, under the same experimental conditions. This is the first step towards the 3D structure determination of the trappin-2. PMID- 26878853 TI - Backbone resonance assignments for the PHD-Bromo dual-domain of the human chromatin reader TRIM24. AB - Plant homeodomains (PHD) and Bromo domains are both chromatin reader domains that recognise histone methylation degree and acetylation state, respectively. The tripartite motif protein TRIM24 is a multidomain protein carrying a PHD-Bromo motif at its C-terminus, through which it is able to bind to histone 3 (H3) N terminal tails with a specific modification pattern, namely unmethylated at K4 and acetylated at K23 (H3-K4me0K23ac). Here we report the 1H, 13C and 15N backbone resonance assignment of this 23 kDa motif, which we have obtained by heteronuclear multidimensional NMR spectroscopy. Furthermore we show that the secondary Calpha and Cbeta chemical shifts are in good agreement with a previously published crystal structure. PMID- 26878855 TI - In silico analysis of Mn transporters (NRAMP1) in various plant species. AB - Manganese (Mn) is an essential micronutrient in plant life cycle. It may be involved in photosynthesis, carbohydrate and lipid biosynthesis, and oxidative stress protection. Mn deficiency inhibits the plant growth and development, and causes the various plant symptoms such as interveinal chlorosis and tissue necrosis. Despite its importance in plant life cycle, we still have limited knowledge about Mn transporters in many plant species. Therefore, this study aimed to identify and characterize high affinity Arabidopsis Mn root transporter NRAMP1 orthologs in 17 different plant species. Various in silico methods and digital gene expression data were used in identification and characterization of NRAMP1 homologs; physico-chemical properties of sequences were calculated, putative transmembrane domains (TMDs) and conserved motif signatures were determined, phylogenetic tree was constructed, 3D models and interactome map were generated, and gene expression data was analyzed. 49 NRAMP1 homologs were identified from proteome datasets of 17 plant species using AtNRAMP1 as query. Identified sequences were characterized with a NRAMP domain structure, 10-12 putative TMDs with cytosolic N- and C-terminuses, and 10-14 exons encoding a protein of 500-588 amino acids and 53.8-64.3 kDa molecular weight with basic characteristics. Consensus transport residues, GQSSTITGTYAGQY(/F)V(/I)MQGFLD(/E/N) between TMD-8 and 9 were identified in all sequences but putative N-linked glycosylation sites were not highly conserved. In phylogeny, NRAMP1 sequences demonstrated divergence in lower and higher plants as well as in monocots and dicots. Despite divergence of lower plant Physcomitrella patens in phylogeny, it showed similarity in superposed 3D models. Phylogenetic distribution of AtNRAMP1 and 6 homologs inferred a functional relationship to NRAMP6 sequences in Mn transport, while distribution of OsNRAMP1 and 5 homologs implicated an involvement of NRAMP1 sequences in Mn transport or a cross-talk between in Fe-Mn homeostasis. Interactome analysis further confirmed this cross talk between Mn and Fe pathways. Gene expression profile of AtNRAMP1 under Fe-, K , P- and S-deficiencies, and cold, drought, heat and salt stresses revealed various proteins involving in transcription regulation, cofactor biosynthesis, diverse developmental roles, carbohydrate metabolism, oxidation-reduction reactions, cellular signaling and protein degradation pathways. Mn deficiency or toxicity could cause serious adverse effects in plants as well as in humans. To reduce these adversities mainly rely on understanding the molecular mechanisms underlying Mn uptake from the soil. However, we still have limited knowledge regarding the structural and functional roles of Mn transporters in many plant species. Therefore, identification and characterization of Mn root uptake transporter, NRAMP1 orthologs in various plant species will provide valuable theoretical knowledge to better understand Mn transporters as well as it may become an insight for future studies aiming to develop genetically engineered and biofortified plants. PMID- 26878856 TI - Possible involvement of miRNAs in tropism of Parvovirus B19. AB - Human Parvovirus B19 (PVB19) is one of the most important pathogens that targets erythroid lineage. Many factors were mentioned for restriction to erythroid progenitor cells (EPCs). Previous studies showed that in non-permissive cells VP1 and VP2 (structural proteins) mRNAs were detected but could not translate to proteins. A bioinformatics study showed that this inhibition might be due to specific microRNAs (miRNAs) present in non-permissive cells but not in permissive EPCs. To confirm the hypothesis, we evaluated the effect of miRNAs on VP expression. CD34(+) HSCs were separated from cord blood. Then, CD34(+) cells were treated with differentiation medium to obtain CD36(+) EPCs. To evaluate the effect of miRNAs on VP expression in MCF7 and HEK-293 cell lines (non-permissive cells) and CD36(+) EPCs, dual luciferase assay was performed in presence of shRNAs against Dicer and Drosha to disrupt miRNA biogenesis. QRT-PCR was performed to check down-regulation of Dicer and Drosha after transfection. All measurements were done in triplicate. Data means were compared using one-way ANOVAs. MicroRNA prediction was done by the online microRNA prediction tools. No significant difference was shown in luciferase activity of CD36(+) EPCs after co transfection with shRNAs, while it was significant in non-permissive cells. Our study revealed that miRNAs may be involved in inhibition of VP expression in non permissive cells, although further studies are required to demonstrate which miRNAs exactly are involved in regulation of PVB19 replication. PMID- 26878858 TI - Internal bone transport using a cannulated screw as a mounting device in the treatment of a post-infective ulnar defect. AB - Bone transport techniques can be used to address the segmental bone loss occurring after debridement for infection. Secure fixation of the bone transport construct to the bone transport segment can be challenging, particularly if the bone is small and osteopenic. We report a case of a segmental ulnar bone defect in a young child treated with internal bone transport using a cannulated screw as the mounting device. We found this technique particularly useful in the treatment of bone loss secondary to infection, where previous treatment and prolonged immobilisation had led to osteopenia. This technique has not been previously reported. PMID- 26878857 TI - Genomics and relative expression analysis identifies key genes associated with high female to male flower ratio in Jatropha curcas L. AB - Jatropha curcas, has been projected as a major source of biodiesel due to high seed oil content (42 %). A major roadblock for commercialization of Jatropha based biodiesel is low seed yield per inflorescence, which is affected by low female to male flower ratio (1:25-30). Molecular dissection of female flower development by analyzing genes involved in phase transitions and floral organ development is, therefore, crucial for increasing seed yield. Expression analysis of 42 genes implicated in floral organ development and sex determination was done at six floral developmental stages of a J. curcas genotype (IC561235) with inherently higher female to male flower ratio (1:8-10). Relative expression analysis of these genes was done on low ratio genotype. Genes TFL1, SUP, AP1, CRY2, CUC2, CKX1, TAA1 and PIN1 were associated with reproductive phase transition. Further, genes CUC2, TAA1, CKX1 and PIN1 were associated with female flowering while SUP and CRY2 in female flower transition. Relative expression of these genes with respect to low female flower ratio genotype showed up to ~7 folds increase in transcript abundance of SUP, TAA1, CRY2 and CKX1 genes in intermediate buds but not a significant increase (~1.25 folds) in female flowers, thereby suggesting that these genes possibly play a significant role in increased transition towards female flowering by promoting abortion of male flower primordia. The outcome of study has implications in feedstock improvement of J. curcas through functional validation and eventual utilization of key genes associated with female flowering. PMID- 26878860 TI - Role of phospholipases in adrenal steroidogenesis. AB - Phospholipases are lipid-metabolizing enzymes that hydrolyze phospholipids. In some cases, their activity results in remodeling of lipids and/or allows the synthesis of other lipids. In other cases, however, and of interest to the topic of adrenal steroidogenesis, phospholipases produce second messengers that modify the function of a cell. In this review, the enzymatic reactions, products, and effectors of three phospholipases, phospholipase C, phospholipase D, and phospholipase A2, are discussed. Although much data have been obtained concerning the role of phospholipases C and D in regulating adrenal steroid hormone production, there are still many gaps in our knowledge. Furthermore, little is known about the involvement of phospholipase A2, perhaps, in part, because this enzyme comprises a large family of related enzymes that are differentially regulated and with different functions. This review presents the evidence supporting the role of each of these phospholipases in steroidogenesis in the adrenal cortex. PMID- 26878859 TI - Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry. AB - BACKGROUND: Grass carp reovirus (GCRV) is responsible for viral hemorrhagic disease in cultured grass carp (Ctenopharyngon idellus). GCRV is a non-enveloped, double-stranded RNA virus in the genus Aquareovirus, of the family Reoviridae, which encodes seven structural proteins (VP1-VP7) and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16). To date, the mechanism of GCRV entry into CIK Ctenopharyngon idellus kidney (CIK) cells remains poorly understood. RESULTS: Here, we present a study of the GCRV internalization mechanism in CIK cells. Our results indicated that GCRV infection was inhibited by chlorpromazine, the specific inhibitor for clathrin-mediated endocytosis. Colocalization of GCRV virions with endogenous clathrin was observed during early infection by confocal microscopy. Moreover, GCRV infection of CIK cells depended on acidification of the endosome. This was indicated by significant inhibition of viral infection following prophylactic treatment with the lysosomotropic drugs chloroquine or ammonium chloride. In addition, the disturbance of dynamin activity blocked GCRV entry, which confirmed the dynamin-dependent nature of clathrin-mediated endocytosis. CONCLUSION: Our findings suggest that GCRV might enter CIK cells via clathrin-mediated endocytosis in a pH-dependent manner. Additionally, dynamin is critical for efficient viral entry. PMID- 26878854 TI - The Histochemistry and Cell Biology omnium-gatherum: the year 2015 in review. AB - We provide here our annual review/synopsis of all of the articles published in Histochemistry and Cell Biology (HCB) for the preceding year. In 2015, HCB published 102 articles, representing a wide variety of topics and methodologies. For ease of access to these differing topics, we have created categories, as determined by the types of articles presented to provide a quick index representing the general areas covered. This year, these categories include: (1) advances in methodologies; (2) molecules in health and disease; (3) organelles, subcellular structures, and compartments; (4) the nucleus; (5) stem cells and tissue engineering; (6) cell cultures: properties and capabilities; (7) connective tissues and extracellular matrix; (8) developmental biology; (9) nervous system; (10) musculoskeletal system; (11) respiratory and cardiovascular system; (12) liver and gastrointestinal tract; and (13) male and female reproductive systems. Of note, the categories proceed from methods development, to molecules, intracellular compartments, stem cells and cell culture, extracellular matrix, developmental biology, and finishing with various organ systems, hopefully presenting a logical journey from methods to organismal molecules, cells, and whole tissue systems. PMID- 26878861 TI - Hodgkin lymphoma: an Australian experience of ABVD chemotherapy in the modern era. AB - Approximately 560 new cases of Hodgkin lymphoma (HL) are diagnosed annually in Australia. Standard first-line therapy is ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). It is unknown how survival outcomes in patients receiving ABVD in current clinical practice, with routine positron emission tomography (PET) imaging and modern supportive measures, compare with results from published trials. This is a retrospective multi-centre study of patients with previously untreated HL between November 1999 and December 2014 receiving ABVD induction. Baseline characteristics, treatment details, toxicity and outcome data were collected from hospital records. The primary endpoint was overall survival (OS). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), response to treatment and toxicity. One hundred and eighty-nine eligible patients were identified. Median age was 32 years (range 17-79). Nodular-sclerosing HL was the most common subtype (78 %), 44 % had B symptoms and 11 % had marrow involvement. Median number of cycles of ABVD administered was 6 (range 3-8). Eighteen patients (11 %) had dose delay, 21 (13 %) had dose reductions and 11 (8 %) had both. The ORR, defined predominantly by PET scan, was 96 % (CR 89 %). Five-year OS and PFS were 93 and 84 %, respectively in early disease (stage I-IIA) and 89 and 63 % in advanced disease (stage IIB, III and IV). No poor prognostic factors were identified on multivariate testing. The most common grade 3/4 toxicity was neutropenia (53 %). Our study confirms the excellent prognosis and manageable toxicity in HL patients receiving ABVD in phase III studies are reflected in patients treated in routine clinical practice in the modern era. PMID- 26878862 TI - Non-bronchial collateral arising from the right vertebral artery: a rare cause of recurrent massive haemoptysis. PMID- 26878864 TI - Nailfold videocapillaroscopy and serum VEGF levels in scleroderma are associated with internal organ involvement. AB - PURPOSE: Nailfold videocapillaroscopy (NVC) identifies the microvascular hallmarks of systemic sclerosis (SSc) and vascular endothelial growth factor (VEGF) and may play a pivotal role in the associated vasculopathy. The aim of the present study was to compare NVC alterations with clinical subsets, internal organ involvement, and serum VEGF levels in a cohort of selected SSc cases. METHODS: We studied 44 patients with SSc who were evaluated within 3 months from enrollment by NVC, skin score, severity index, pulmonary function tests, carbon monoxide diffusing capacity (DLCO), echocardiography, pulmonary high-resolution computed tomography (HRCT), gastroesophageal (GE) endoscopy or manometry or X ray, and serum autoantibodies. Serum VEGF-A levels were determined by ELISA in 72 SSc patients and 31 healthy controls. RESULTS: Giant capillaries were inversely correlated with age (p = 0.034, r = -0.34) and to the extent of reticular pattern at HRCT (p = 0.04, r = -0.5). Avascular areas were directly correlated with capillaroscopy skin ulcer risk index (CSURI) (p = 0.006, r = +0.4) and severity index (p = 0.004, r = +0.5). The mean capillary density was directly correlated to the ulcer number (p = 0.02, r = +0.4) and to DLCO/alveolar volume (p = 0.02, r = +0.4) and inversely correlated with severity index (p = 0.01, r = -0.4) and skin score (p = 0.02, r = -0.4). Serum VEGF levels were higher in the SSc population vs controls (p = 0.03) and inversely correlated with DLCO (p = 0.01, r =-0.4) and directly with ground-glass and reticular pattern at HRCT (p = 0.04, r = +0.4 for both). CONCLUSIONS: Our data suggest the importance of NVC not only for the diagnosis, but also for the global evaluation of SSc patients. Of note, serum VEGF levels may act as a biomarker of interstitial lung involvement. PMID- 26878865 TI - Barriers to Managing Fertility: Findings From the Understanding Fertility Management in Contemporary Australia Facebook Discussion Group. AB - BACKGROUND: As part of research investigating the complexities of managing fertility in Australia, public opinions about how Australians manage their fertility were sought from women and men. OBJECTIVE: To identify public opinion about sexual and reproductive health in Australia. METHODS: To ensure access to a diverse group of people throughout Australia, an online group was advertised and convened on Facebook from October through December 2013. In a closed-group moderated discussion, participants responded to questions about how people in Australia attempt to manage three aspects of fertility: avoiding pregnancy, achieving pregnancy, and difficulties conceiving. Nonidentifiable demographic information was sought; no personal accounts of fertility management were requested. The discussion transcript was analyzed thematically. RESULTS: There were 61 female and 2 male Facebook users aged 18 to 50 years living in Australia participating in the study. Four main themes about fertility management were identified: access, geographical location, knowledge, and cost. Participants reported that young people and people from rural areas face barriers accessing contraception and fertility services. Limited knowledge about sex and reproduction and the cost of fertility services and contraception were also said to impede effective fertility management. CONCLUSIONS: Reasons for inequalities in effective fertility management that are amenable to change were identified. Facebook is an effective method for gaining insights into public opinion about sexual and reproductive health. PMID- 26878863 TI - Growing older with health and vitality: a nexus of physical activity, exercise and nutrition. AB - The preservation of skeletal muscle mass and strength with advancing age are, we propose, critical aspects of ageing with health and vitality. Physical inactivity and poor nutrition are known to accelerate the gradual age-related decline in muscle mass and strength-sarcopenia-however, both are subject to modification. The main purpose of this review is to present the latest, evidence-based recommendations for physical activity and exercise, as well as diet for older adults that would help in preserving muscle mass and strength. We take the position that future physical activity/exercise guidelines need to make specific reference to resistance exercise and highlight the benefits of higher-intensity aerobic exercise training, alongside advocating older adults perform aerobic based physical activity and household tasks (e.g., carrying groceries). In terms of dietary recommendations, greater emphasis should be placed on optimal rather than minimum protein intakes for older adults. Indeed, guidelines that endorse a daily protein intake of 1.2-1.5 g/kg BM/day, which are levels 50-90 % greater than the current protein Recommendation Dietary Allowance (0.8 g/kg BM/day), are likely to help preserve muscle mass and strength and are safe for healthy older adults. Being cognisant of factors (e.g., reduced appetite) that may preclude older adults from increasing their total daily protein intake, we echo the viewpoint of other active researchers in advocating that protein recommendations for older adults be based on a per meal approach in order to maximize muscle protein synthesis (MPS). On this basis, assuming three meals are consumed daily, a protein dose of 0.4-0.5 g/kg BM should be contained in each meal. We are beginning to understand ways in which to increase the utilization of ingested protein for the stimulation of MPS, namely by increasing the proportion of leucine contained in a given dose of protein, co-ingesting other nutrients (e.g., carbohydrate and fat or supplementation with n-3 polyunsaturated fatty acids) or being physically active prior to protein intake. Clearly, developing simple lifestyle interventions targeted at preserving muscle mass and strength with advancing age is crucial for facilitating longer, healthier lives into older age. PMID- 26878868 TI - The Desires of Their Hearts: The Multidisciplinary Perspectives of African Americans on End-of-Life Care in the African American Community. AB - BACKGROUND: Studies have identified racial differences in advance care planning and use of hospice for care at the end of life. Multiple reasons for underuse among African American patients and their families have been proposed and deserve further exploration. OBJECTIVE: The goal of this study was to examine perceptions of advance care planning, palliative care, and hospice among a diverse sample of African Americans with varying degrees of personal and professional experience with end-of-life care and use these responses to inform a culturally sensitive intervention to promote awareness of these options. METHODS: Semistructured interviews and focus groups were conducted with African Americans who had varying degrees of experience and exposure to end-of-life care both personally and professionally. We conducted in-depth qualitative analyses of these interviews and focus group transcripts and determined that thematic saturation had been achieved. RESULTS: Several themes emerged. Participants felt that advance care planning, palliative care, and hospice can be beneficial to African American patients and their families but identified specific barriers to completion of advance directives and hospice enrollment, including lack of knowledge, fear that these measures may hasten death or cause providers to deliver inadequate care, and perceived conflict with patients' faith and religious beliefs. Providers described approaches they use to address these barriers in their practices. CONCLUSION: Findings, which are consistent with and further elucidate those identified from previous research, will inform design of a culturally sensitive intervention to increase awareness and understanding of advance care planning, palliative care, and hospice among members of the African American community. PMID- 26878866 TI - Carbamylated LL-37 as a modulator of the immune response. AB - Carbamylation of lysine residues and protein N-termini is an ubiquitous, non enzymatic post-translational modification. Carbamylation at sites of inflammation is due to cyanate formation during the neutrophil oxidative burst and may target lysine residues within the antimicrobial peptide LL-37. The bactericidal and immunomodulatory properties of LL-37 depend on its secondary structure and cationic nature, which are conferred by arginine and lysine residues. Therefore, carbamylation may affect the biological functions of LL-37. The present study examined the kinetics and pattern of LL-37 carbamylation to investigate how this modification affects the bactericidal, cytotoxic and immunomodulatory function of the peptide. The results indicated that LL-37 undergoes rapid modification in the presence of physiological concentrations of cyanate, yielding a spectrum of diverse carbamylated peptides. Mass spectrometry analyses revealed that theN terminal amino group of Leu-1 was highly reactive and was modified almost instantly by cyanate to generate the predominant form of the modified peptide, named LL-37(C1) This was followed by the sequential carbamylation of Lys-8, Lys 12, and Lys-15 to yield LL-37(C8), and Lys-15 to yield LL-37(C12,15) Carbamylation had profound and diverse effects on the structure and biological properties of LL-37. In some cases, anti-inflammatory LL-37 was rapidly converted to pro-inflammatory LL-37. PMID- 26878867 TI - Resolvin D1, resolvin D2 and maresin 1 activate the GSK3beta anti-inflammatory axis in TLR4-engaged human monocytes. AB - Pro-resolving, docosahexaenoic acid-derived mediators have recently emerged as important potential therapeutic agents for the amelioration of complications arising from inflammation, such as vascular disease, asthma, acute lung injury and colitis. While resolvin D1 (RVD1), resolvin D2 (RVD2) and maresin 1 (MaR1) are established pro-resolvins, their mechanisms of action remain unclear. Here we show that, in LPS-stimulated primary human monocytes, RVD1, RVD2 and MaR1 each suppress the release of pro-inflammatory cytokines (TNF, IL-1beta, IL-8) and the innate/adaptive bridging cytokine, IL-12 p40, while simultaneously augmenting the production of the anti-inflammatory cytokine, IL-10. Such resolving activity is accompanied by the increased phosphorylation (enhanced anti-inflammatory state) of glycogen synthase kinase 3beta (GSK3beta) along with increased phosphorylation (activation) of Akt, SGK1 and CREB but not MAPK-related molecules. Gain and loss of function experiments confirm a key role for GSK3beta and CREB in the anti inflammatory actions of resolvins. These results suggest that induction of the GSK3beta anti-inflammatory axis is a common mechanism of action for RVD1, RVD2 and MaR1. PMID- 26878869 TI - Exploring Health Care Providers' Views About Initiating End-of-Life Care Communication. AB - Numerous factors impede effective and timely end-of-life (EOL) care communication. These factors include delays in communication until patients are seriously ill and/or close to death. Gaps in patient-provider communication negatively affect advance care planning and limit referrals to palliative and hospice care. Confusion about the roles of various health care providers also limits communication, especially when providers do not coordinate care with other health care providers in various disciplines. Although providers receive education regarding EOL communication and care coordination, little is known about the roles of all health care providers, including nonphysician support staff working with physicians to discuss the possibility of dying and help patients prepare for death. This study explores the perspectives of physicians, nurses, social workers, and chaplains on engaging seriously ill patients and families in EOL care communication. Qualitative data were from 79 (medical and nonmedical) providers practicing at 2 medical centers in Central Los Angeles. Three themes that describe providers' perceptions of their roles and responsibility in talking with seriously ill patients emerged: (1) providers' roles for engaging in EOL discussions, (2) responsibility of physicians for initiating and leading discussions, and (3) need for team co-management patient care. Providers highlighted the importance of beginning discussions early by having physicians lead them, specifically due to their medical training and need to clarify medical information regarding patients' prognosis. Although physicians are a vital part of leading EOL communication, and are at the center of communication of medical information, an interdisciplinary approach that involves nurses, social workers, and chaplains could significantly improve patient care. PMID- 26878870 TI - Evolutionary Relationships among Extinct and Extant Sloths: The Evidence of Mitogenomes and Retroviruses. AB - Macroevolutionary trends exhibited by retroviruses are complex and not entirely understood. The sloth endogenized foamy-like retrovirus (SloEFV), which demonstrates incongruence in virus-host evolution among extant sloths (Order Folivora), has not been investigated heretofore in any extinct sloth lineages and its premodern history within folivorans is therefore unknown. Determining retroviral coevolutionary trends requires a robust phylogeny of the viral host, but the highly reduced modern sloth fauna (6 species in 2 genera) does not adequately represent what was once a highly diversified clade (~100 genera) of placental mammals. At present, the amount of molecular data available for extinct sloth taxa is limited, and analytical results based on these data tend to conflict with phylogenetic inferences made on the basis of morphological studies. To augment the molecular data set, we applied hybridization capture and next generation Illumina sequencing to two extinct and three extant sloth species to retrieve full mitochondrial genomes (mitogenomes) from the hosts and the polymerase gene of SloEFV. The results produced a fully resolved and well supported phylogeny that supports dividing crown families into two major clades: 1) The three-toed sloth, Bradypus, and Nothrotheriidae and 2) Megalonychidae, including the two-toed sloth, Choloepus, and Mylodontidae. Our calibrated time tree indicates that the Miocene epoch (23.5 Ma), particularly its earlier part, was an important interval for folivoran diversification. Both extant and extinct sloths demonstrate multiple complex invasions of SloEFV into the ancestral sloth germline followed by subsequent introgressions across different sloth lineages. Thus, sloth mitogenome and SloEFV evolution occurred separately and in parallel among sloths. PMID- 26878871 TI - Gene Family Expansions in Aphids Maintained by Endosymbiotic and Nonsymbiotic Traits. AB - Facilitating the evolution of new gene functions, gene duplication is a major mechanism driving evolutionary innovation. Gene family expansions relevant to host/symbiont interactions are increasingly being discovered in eukaryotes that host endosymbiotic microbes. Such discoveries entice speculation that gene duplication facilitates the evolution of novel, endosymbiotic relationships. Here, using a comparative transcriptomic approach combined with differential gene expression analysis, we investigate the importance of endosymbiosis in retention of amino acid transporter paralogs in aphid genomes. To pinpoint the timing of amino acid transporter duplications we inferred gene phylogenies for five aphid species and three outgroups. We found that while some duplications arose in the aphid common ancestor concurrent with endosymbiont acquisition, others predate aphid divergence from related insects without intracellular symbionts, and still others appeared during aphid diversification. Interestingly, several aphid specific paralogs have conserved enriched expression in bacteriocytes, the insect cells that host primary symbionts. Conserved bacteriocyte enrichment suggests that the transporters were recruited to the aphid/endosymbiont interface in the aphid common ancestor, consistent with a role for gene duplication in facilitating the evolution of endosymbiosis in aphids. In contrast, the temporal variability of amino acid transporter duplication indicates that endosymbiosis is not the only trait driving selection for retention of amino acid transporter paralogs in sap-feeding insects. This study cautions against simplistic interpretations of the role of gene family expansion in the evolution of novel host/symbiont interactions by further highlighting that multiple complex factors maintain gene family paralogs in the genomes of eukaryotes that host endosymbiotic microbes. PMID- 26878873 TI - MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells. AB - BACKGROUND: Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy) is induced, these cells are chemosensitive and will not recover following chemotherapy treatment. In contrast, when cancer cells exhibit only autophagy and limited Type II cell death, they are chemoresistant and recover following drug withdrawal. METHODS: MicroRNA (miRNA) expression profiling of an oesophageal cancer cell line panel was used to identify miRNAs that were important in the regulation of apoptosis and autophagy. The effects of miRNA overexpression on cell death mechanisms and recovery were assessed in the chemoresistant (autophagy inducing) KYSE450 oesophageal cancer cells. RESULTS: MiR-193b was the most differentially expressed miRNA between the chemosensitive and chemoresistant cell lines with higher expression in chemosensitive apoptosis inducing cell lines. Colony formation assays showed that overexpression of miR-193b significantly impedes the ability of KYSE450 cells to recover following 5-fluorouracil (5-FU) treatment. The critical mRNA targets of miR-193b are unknown but target prediction and siRNA data analysis suggest that it may mediate some of its effects through stathmin 1 regulation. Apoptosis was not involved in the enhanced cytotoxicity. Overexpression of miR-193b in these cells induced autophagic flux and non apoptotic cell death. CONCLUSION: These results highlight the importance of miR 193b in determining oesophageal cancer cell viability and demonstrate an enhancement of chemotoxicity that is independent of apoptosis induction. PMID- 26878874 TI - Comparison of clinical grade human platelet lysates for cultivation of mesenchymal stromal cells from bone marrow and adipose tissue. AB - BACKGROUND: The utility of mesenchymal stromal cells (MSCs) in therapeutic applications for regenerative medicine has gained much attention. Clinical translation of MSC-based approaches requires in vitro culture-expansion to achieve a sufficient number of cells. The ideal cell culture medium should be devoid of any animal derived components. We have evaluated whether human Platelet Lysate (hPL) could be an attractive alternative to animal supplements. METHODS: MSCs from bone marrow (BMSCs) and adipose tissue-derived stromal cells (ASCs) obtained from three donors were culture expanded in three different commercially available hPL fulfilling good manufacturing practice criteria for clinical use. BMSCs and ASCs cultured in Minimum Essential Medium Eagle-alpha supplemented with 5% PLT-Max (Mill Creek), StemulateTM PL-S and StemulateTM PL-SP (COOK General Biotechnology) were compared to standard culture conditions with 10% fetal bovine serum (FBS). Cell morphology, proliferation, phenotype, genomic stability, and differentiation potential were analyzed. RESULTS: Regardless of manufacturer, BMSCs and ASCs cultured in hPL media showed a significant increase in proliferation capacity compared to FBS medium. In general, the immunophenotype of both BMSCs and ASCs fulfilled International Society for Cellular Therapy (ISCT) criteria after hPL media expansion. Comparative genomic hybridization measurements demonstrated no unbalanced chromosomal rearrangements for BMSCs or ASCs cultured in hPL media or FBS medium. The BMSCs and ASCs could differentiate into osteogenic, adipogenic, or chondrogenic lineages in all four culture conditions. CONCLUSION: All three clinically approved commercial human platelet lysates accelerated proliferation of BMSCs and ASCs and the cells meet the ISCT mesenchymal phenotypic requirements without exhibiting chromosomal aberrations. PMID- 26878875 TI - Specific allergen immunotherapy: effect on IgE, IgG4 and chemokines in patients with allergic rhinitis. AB - BACKGROUND: Allergen-specific immunotherapy (SIT) is considered as the most effective treatment for Immunoglobulin E (IgE)-mediated allergies. However, how specific immunotherapy attenuates allergic responses is still not clear, but could potentially involve cytokines as well as IgG4-mediated responses. Based on the role of chemokines in IgE-mediated inflammation, we examined the SIT-induced chemokine response in patients with allergic rhinitis. METHODS: We included 35 patients with allergic rhinitis; 20 patients received SIT and 15 patients were not treated with specific immunotherapy. The patients were followed for 3 years. Blood samples were collected before SIT and 3, 5, 7 and 21 weeks and 1, 2 and 3 years after the start of therapy. Total IgE, specific IgE, IgG4 and chemokine levels were assessed. RESULTS: Our main findings were: (i) SIT was associated with an early increase in total and specific IgE during the first 7 weeks, with a subsequent decline, accompanied by a marked increase in specific IgG4 when IgE started to decline; (ii) these SIT-induced responses were accompanied by and in some degree correlated with increased plasma concentrations of the chemokines, monocyte chemoattractant protein (MCP)-1, and eotaxin; and (iii) within the SIT group, these correlations with chemokines were restricted to IgE and IgG4 against birch tree pollen. CONCLUSION: Our findings further support a role for IgG4 mediated mechanisms in the beneficial effects of SIT in patients with allergic rhinitis (AR) and that increased levels of certain chemokines also could be of importance for the effect of such therapy. PMID- 26878876 TI - Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test. AB - BACKGROUND: Histological examination of small bowel biopsies is normally the gold standard for the diagnosis of celiac disease (CD). The objective of this study was to investigate whether the rate of decreases in elevated plasma IgA tissue transglutaminase antibody (IgA-tTG) and/or IgG deamidated gliadin peptides antibody (IgG - DGP) concentrations could be used as a confirming test for CD in children on a gluten-free diet (GFD) when biopsy was omitted in the diagnostic process. METHODS: In this retrospective study we compared children (<=18 years old) with a CD-confirming biopsy (n = 16) to children without a biopsy (n = 18). After initiation of GFD the antibody half-life (the time (T1/2) when the antibody concentration is 50% decreased) was determined in all children. RESULTS: Children with a biopsy (IgA-tTG, T1/2 = 1.9 months; IgG - DGP, T1/2 = 2.2 months) and children without a biopsy (IgA-tTG, T1/2 = 1.6 months; IgG - DGP, T1/2 = 2.7 months) had comparable T1/2 (mean) results (p < 0.05) supporting that all children had the CD diagnosis. CONCLUSIONS: When biopsy was omitted a rapid rate of decrease in CD antibody concentrations confirmed the CD diagnosis in children on GFD. The half-lives (T1/2) of IgA-tTG were less than 2 months in CD children. PMID- 26878877 TI - Aspartate aminotransferase to platelet ratio index - a reliable predictor of therapeutic efficacy and improvement of Ishak score in chronic hepatitis B patients treated with nucleoside analogues. AB - BACKGROUND: No studies have investigated the predictive and monitoring efficacy of aspartate aminotransferase to platelet ratio index in chronic hepatitis B patients undergoing antiviral therapy based on paired Ishak biopsies pre- and post-treatment. We evaluated the efficacy of aspartate aminotransferase to platelet ratio index in monitoring fibrosis improvement in chronic hepatitis B patients treated with nucleoside analogue or interferon. METHODS: Pre- and post treatment Ishak fibrosis scores of 86 nucleoside-analogue- and 42 interferon treated patients were retrospectively analyzed. The area under the receiver operating characteristic curve was calculated. RESULTS: In nucleoside-analogue treated patients, the area under the receiver operating characteristic curve was 0.80 and 0.91 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis and cirrhosis, respectively. When the decreased magnitude of aspartate aminotransferase to platelet ratio index was >= 0.35, the sensitivity and specificity of predicting fibrosis improvement were 75.8% and 75.0%, respectively. The area under the receiver operating characteristic curve was 0.53 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis in 20 interferon-treated patients, while an insufficient patient number in the cirrhosis group prevented the calculation of the area under the receiver operating characteristic curve. The same is true for the remaining 22 interferon treated patients. CONCLUSIONS: Our study is the first to demonstrate the aspartate aminotransferase to platelet ratio index as a reliable marker in diagnosing and monitoring fibrosis improvement in nucleoside-analogue-treated patients based on paired Ishak biopsies pre- and post-treatment, but the test is not applicable in interferon therapy. PMID- 26878872 TI - p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function. AB - The role of p53 family member p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63 monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell like DLBCL patients with wide- type TP53. The prognostic impact in germinal center-B-cell-like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ?Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations. PMID- 26878879 TI - Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer's disease. AB - BACKGROUND/AIMS: Deregulation of metal ion homeostasis has been assumed as one of the key factors in the progression of neurodegenerative diseases. Aluminium (Al) has been believed as a major risk factor for the cause and progression of Alzheimer's disease (AD). In our lab, we have previously reported that hesperidin, a citrus bioflavonoid reversed memory loss caused by aluminium intoxication through attenuating acetylcholine esterase activity and the expression of Amyloid beta biosynthesis related markers. Al has been reported to cause oxidative stress associated apoptotic neuronal loss in the brain. So in the present study, protective effect of hesperidin against aluminium chloride (AlCl3) induced cognitive impairment, oxidative stress and apoptosis was studied. METHODS: Male Wistar rats were divided into control, AlCl3 treated (100 mg/kg., b.w.), AlCl3 and hesperidin (100 mg/kg., b.w.) co-treated and hesperidin alone treated groups. In control and experimental rats, learning and memory impairment were measured by radial arm maze, elevated plus maze and passive avoidance tests. In addition, oxidative stress and expression of pro and anti-apoptotic markers were also evaluated. RESULTS: Intraperitoneal injection of AlCl3 (100 mg/kg., b.w.) for 60 days significantly enhanced the learning and memory deficits, levels of thiobarbituric acid reactive substances and the expression of Bax and diminished the levels of reduced glutathione, activities of enzymatic antioxidants and the expression of B-cell lymphoma-2 (Bcl-2) as compared to control group in the hippocampus, cortex, and cerebellum. Coadministration of hesperidin (100 mg/kg., b.w. oral) for 60 days prevented the cognitive deficits, biochemical anomalies and apoptosis induced by AlCl3 treatment. CONCLUSION: Results of the present study demonstrated that hesperidin could be a potential therapeutic agent in the treatment of oxidative stress and apoptosis associated neurodegenerative diseases including AD. PMID- 26878880 TI - Smart Magnetic Nanosensors Synthesized through Layer-by-Layer Deposition of Molecular Beacons for Noninvasive and Longitudinal Monitoring of Cellular mRNA. AB - Noninvasive and longitudinal monitoring of gene expression in living cells is essential for understanding and monitoring cellular activities. Herein, a smart magnetic nanosensor is constructed for the real-time, noninvasive, and longitudinal monitoring of cellular mRNA expression through the layer-by-layer deposition of molecular beacons (MBs) and polyethylenimine on the iron oxide nanoparticles. The loading of MBs, responsible for the signal intensity and the tracking time, was easily tuned with the number of layers incorporated. The idea was first demonstrated with the magnetic nanosensors for glyceraldehyde-3 phosphate dehydrogenase (GAPDH) mRNA, which was efficiently internalized into the cells under the influence of magnetic field. This nanosensor allowed the continuous monitoring of the cellular GAPDH mRNA expression for 1 month. Then this platform was further utilized to incorporate two kinds of MBs for alkaline phosphatase (ALP) and GAPDH mRNAs, respectively. The multifunctional nanosensors permitted the simultaneous monitoring of the reference gene (GAPDH mRNA) and the early osteogenic differentiation marker (ALP mRNA) expression. When the fluorescence signal ratio between ALP mRNA MBs and GAPDH mRNA MBs was taken, the dynamic osteogenic differentiation process of MSCs was accurately monitored. PMID- 26878881 TI - Water and beverage consumption among children aged 4-13 years in France: analyses of INCA 2 (Etude Individuelle Nationale des Consommations Alimentaires 2006-2007) data. AB - OBJECTIVE: To examine the consumption of plain water among children in France and compare total water intakes with guidelines issued by the European Food Safety Authority (EFSA). DESIGN: Nationally representative data were used to assess food, beverage and water consumption by sex, age group (4-8 years, 9-13 years), income-to-poverty ratio, eating occasion and location. Beverages were classified into nine groups: water (tap or bottled), milk, 100 % fruit juice, sodas, fruit drinks, hot beverages, sports drinks and flavoured waters. Total water volume in relation to energy intake (litres/kcal) was also examined. SETTING: INCA 2 study (Etude Individuelle Nationale des Consommations Alimentaires 2006-2007). SUBJECTS: French children (n 835) aged 4-13 years. RESULTS: Total water intakes were accounted for by plain water (34 %), beverages (26 %) and food moisture (40 %). Plain water could be tap (18 %) or bottled (16 %). Older children drank more plain water than did younger children and boys drank more plain water than did girls. No socio-economic gradient for plain water consumption was observed. About 90 % of children did not meet the EFSA water intake recommendations. The daily water shortfall ranged from 367 to 594 ml/d. Water-to-energy ratio was 0.75-0.77 litres/1000 kcal (4184 kJ). Children drank milk at breakfast and plain water during lunch and dinner. Caloric beverages provided 10 % of dietary energy; consumption patterns varied by eating location. CONCLUSIONS: Total water intakes among young children in France were below EFSA-recommended levels. Analyses of beverage consumption patterns by eating occasion and location can help identify ways to increase water consumption among children. PMID- 26878882 TI - Isoflavone metabolism by a collection of lactic acid bacteria and bifidobacteria with biotechnological interest. AB - Almost all soy isoflavones exist as glycosides, daidzin, genistin, and glycitin. We analyzed the capacity of 92 strains of lactic acid bacteria (LAB) and bifidobacteria with biotechnological interest to process the glycosylated isoflavones daidzin, genistin, and glycitin in their more bioavailable aglycones and their metabolites as dihydrodaidzein (DHD), O-desmethylangolensin, and equol. Representative strains of the four genera studied Lactobacillus, Enterococcus, Lactococcus, and Bifidobacterium were able to produce daidzein, genistein, and glycitein, with the exception of the lactobacilli, which did not produced glycitein in soy extracts. The production of the aglycone isoflavones could be correlated with the beta-glucosidase activity of the strains. The isoflavone metabolism is limited to the glycoside hydrolysis in the most of these strains. Moreover, Enterococcus faecalis INIA P333 and Lactobacillus rhamnosus INIA P540 were able to transform daidzein in DHD. LAB and bifidobacteria studied in the present work have a great potential in the metabolism of isoflavones and could be selected for the development of functional fermented soy foods. PMID- 26878883 TI - Native Chemical Ligation Strategy to Overcome Side Reactions during Fmoc-Based Synthesis of C-Terminal Cysteine-Containing Peptides. AB - The Fmoc-based solid phase synthesis of C-terminal cysteine-containing peptides is problematic, due to side reactions provoked by the pronounced acidity of the Calpha proton of cysteine esters. We herein describe a general strategy consisting of the postsynthetic introduction of the C-terminal Cys through a key chemoselective native chemical ligation reaction with N-Hnb-Cys peptide crypto thioesters. This method was successfully applied to the demanding peptide sequences of two natural products of biological interest, giving remarkably high overall yields compared to that of a state of the art strategy. PMID- 26878884 TI - A first-principles study on the phonon transport in layered BiCuOSe. AB - First-principles calculations are employed to investigate the phonon transport of BiCuOSe. Our calculations reproduce the lattice thermal conductivity of BiCuOSe. The calculated gruneisen parameter is 2.4 ~ 2.6 at room temperature, a fairly large value indicating a strong anharmonicity in BiCuOSe, which leads to its ultralow lattice thermal conductivity. The contribution to total thermal conductivity from high-frequency optical phonons, which are mostly contributed by the vibrations of O atoms, is larger than 1/3, remarkably different from the usual picture with very little contribution from high-frequency optical phonons. Our calculations show that both the high group velocities and low scattering processes involved make the high-frequency optical modes contribute considerably to the total lattice thermal conductivity. In addition, we show that the sound velocity and bulk modulus along a and c axes exhibit strong anisotropy, which results in the anisotropic thermal conductivity in BiCuOSe. PMID- 26878885 TI - Post mTBI fatigue is associated with abnormal brain functional connectivity. AB - This study set out to investigate the behavioral correlates of changes in resting state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID- 26878886 TI - Morpholino-mediated SOD1 reduction ameliorates an amyotrophic lateral sclerosis disease phenotype. AB - Neurotoxicity due to the accumulation of mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Mutations in superoxide dismutase 1 (SOD1) are linked to familial amyotrophic lateral sclerosis (fALS); these mutations result in progressive motor neuron death through one or more acquired toxicities. Interestingly, SOD1 is not only responsible for fALS but may also play a significant role in sporadic ALS; therefore, SOD1 represents a promising therapeutic target. Here, we report slowed disease progression, improved neuromuscular function, and increased survival in an in vivo ALS model following therapeutic delivery of morpholino oligonucleotides (MOs) designed to reduce the synthesis of human SOD1. Neuropathological analysis demonstrated increased motor neuron and axon numbers and a remarkable reduction in astrogliosis and microgliosis. To test this strategy in a human model, we treated human fALS induced pluripotent stem cell (iPSC)-derived motor neurons with MOs; these cells exhibited increased survival and reduced expression of apoptotic markers. Our data demonstrated the efficacy of MO-mediated therapy in mouse and human ALS models, setting the stage for human clinical trials. PMID- 26878887 TI - Competition in the presence of aging: dominance, coexistence, and alternation between states. AB - We study the stochastic dynamics of coupled states with transition probabilities depending on local persistence, this is, the time since a state has changed. When the system has a preference to adopt older states the system orders quickly due to the dominance of old states. When preference for new states prevails, the system can show coexistence of states or synchronized collective behavior resulting in long ordering times. In this case, the magnetization of the system oscillates around zero. Finally we discuss a potential application in social systems. PMID- 26878888 TI - Quantitative molecular phenotyping with topically applied SERS nanoparticles for intraoperative guidance of breast cancer lumpectomy. AB - There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15 minutes for potential intraoperative use in guiding breast conserving surgeries. PMID- 26878889 TI - Appearance of beta-lactam Resistance Genes in Agricultural Soils and Clinical Isolates over the 20th Century. AB - Debate exists about whether agricultural versus medical antibiotic use drives increasing antibiotic resistance (AR) across nature. Both sectors have been inconsistent at antibiotic stewardship, but it is unclear which sector has most influenced acquired AR on broad scales. Using qPCR and soils archived since 1923 at Askov Experimental Station in Denmark, we quantified four broad-spectrum beta lactam AR genes (ARG; bla(TEM), bla(SHV), bla(OXA) and bla(CTX-M)) and class-1 integron genes (int1) in soils from manured (M) versus inorganic fertilised (IF) fields. "Total" beta-lactam ARG levels were significantly higher in M versus IF in soils post-1940 (paired-t test; p < 0.001). However, dominant individual ARGs varied over time; bla(TEM) and bla(SHV) between 1963 and 1974, bla(OXA) slightly later, and bla(CTX-M) since 1988. These dates roughly parallel first reporting of these genes in clinical isolates, suggesting ARGs in animal manure and humans are historically interconnected. Archive data further show when non-therapeutic antibiotic use was banned in Denmark, bla(CTX-M) levels declined in M soils, suggesting accumulated soil ARGs can be reduced by prudent antibiotic stewardship. Conversely, int1 levels have continued to increase in M soils since 1990, implying direct manure application to soils should be scrutinized as part of future stewardship programs. PMID- 26878890 TI - A new ether-based electrolyte for dendrite-free lithium-metal based rechargeable batteries. AB - A new ether-based electrolyte to match lithium metal electrode is prepared by introducing 1, 4-dioxane as co-solvent into lithium bis(fluorosulfonyl)imide/1,2 dimethoxyethane solution. Under the synergetic effect of solvents and salt, this simple liquid electrolyte presents stable Li cycling with dendrite-free Li deposition even at relatively high current rate, high coulombic efficiency of ca. 98%, and good anodic stability up to ~4.87 V vs Li RE. Its excellent performance will open up a new possibility for high energy-density rechargeable Li metal battery system. PMID- 26878892 TI - Adult neurogenesis in the human striatum: possible implications for psychiatric disorders. PMID- 26878893 TI - Diagnostic Accuracy of Transcranial Sonography of the Substantia Nigra in Parkinson's disease: A Systematic Review and Meta-analysis. AB - A large number of articles have reported substantia nigra hyperechogenicity in Parkinson's disease (PD) and have assessed the diagnostic accuracy of transcranial sonography (TCS); however, the conclusions are discrepant. Consequently, this systematic review and meta-analysis aims to consolidate the available observational studies and provide a comprehensive evaluation of the clinical utility of TCS in PD. Totally, 31 studies containing 4,386 participants from 13 countries were included. A random effects model was utilized to pool the effect sizes. Meta-regression and sensitivity analysis were performed to explore potential heterogeneity. Overall diagnostic accuracy of TCS in differentiating PD from normal controls was quite high, with a pooled sensitivity of 0.83 (95% CI: 0.81-0.85) and a pooled specificity of 0.87 (95% CI: 0.85-0.88). The positive likelihood ratio, the negative likelihood ratio and diagnostic odds ratio were calculated 6.94 (95% CI: 5.09-9.48), 0.19 (95% CI: 0.16-0.23), and 42.89 (95% CI: 30.03-61.25) respectively. Our systematic review of the literature and meta analysis suggest that TCS has high diagnostic accuracy in the diagnosis of PD when compared to healthy control. PMID- 26878895 TI - Erratum: PBK/TOPK enhances aggressive phenotype in prostate cancer via beta catenin-TCF/LEF-mediated matrix metalloproteinases production and invasion. PMID- 26878894 TI - The Efficacy of Three Modalities of Internet-Based Psychotherapy for Non Treatment-Seeking Online Problem Gamblers: A Randomized Controlled Trial. AB - BACKGROUND: Internet-based interventions targeted at the most at-risk gamblers could reduce the treatment gap for addictive disorders. Currently, no clinical trial has included non-treatment-seeking patients who have been recruited directly in their gambling environment. This study was the first exclusively Internet-based randomized controlled trial among non-help-seeking problem gamblers with naturalistic recruitment in their gambling environment. OBJECTIVE: The aim of this study was to assess the efficacy of three modalities of Internet based psychotherapies with or without guidance, compared to a control condition, among problem gamblers who play online poker. METHODS: All active poker gamblers on the Winamax website were systematically offered screening. All problem poker gamblers identified with a Problem Gambling Severity Index (PGSI) score of >= 5 were eligible to be included in the trial. Problem gamblers were randomized into four groups: (1) waiting list (control group), (2) personalized normalized feedback on their gambling status by email, (3) an email containing a self-help book to be downloaded with a Cognitive Behavioral Therapy (CBT) program without guidance, and (4) the same CBT program emailed weekly by a trained psychologist with personalized guidance. Efficacy was assessed based on the change in PGSI between baseline and 6 weeks (end of treatment) or 12 weeks (maintenance) and supported by player account-based gambling data automatically collected at the three time points. RESULTS: All groups met high attrition rates (83%), but the group with guidance had a significantly higher dropout rate than the other three groups, including the control group. Although all groups showed some improvement, with a mean decrease of 1.35 on the PGSI, no significant difference in efficacy between the groups was observed. One-third of the problem gamblers fell below the problem gambling threshold at 6 weeks. CONCLUSIONS: Guidance could have aversively affected problem gamblers who had not sought help. Despite the lack of significant difference in efficacy between groups, this naturalistic trial provides a basis for the development of future Internet-based trials in individuals with gambling disorders. Comorbidities, natural course of illness, and intrinsic motivation seem to be critical issues to consider in future designs. TRIAL REGISTRATION: ANSM 2013-A00794-41. PMID- 26878891 TI - Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders. AB - The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic pituitary-adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases. PMID- 26878897 TI - Mapping the interplay among cognitive biases, emotion regulation, and depressive symptoms. AB - Cognitive biases and emotion regulation (ER) difficulties have been instrumental in understanding hallmark features of depression. However, little is known about the interplay among these important risk factors to depression. This cross sectional study investigated how multiple cognitive biases modulate the habitual use of ER processes and how ER habits subsequently regulate depressive symptoms. All participants first executed a computerised version of the scrambled sentences test (interpretation bias measure) while their eye movements were registered (attention bias measure) and then completed questionnaires assessing positive reappraisal, brooding, and depressive symptoms. Path and bootstrapping analyses supported both direct effects of cognitive biases on depressive symptoms and indirect effects via the use of brooding and via the use of reappraisal that was in turn related to the use of brooding. These findings help to formulate a better understanding of how cognitive biases and ER habits interact to maintain depressive symptoms. PMID- 26878896 TI - Ocular surface findings in patients with rheumatoid arthritis under methotrexate or biological agent therapy. AB - PURPOSE: To evaluate the ocular findings in patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) or MTX with biological agents. METHODS: One hundred and twelve eyes of 56 patients with RA and treated with MTX or MTX with biological agents were included in the study. Patients were divided into two groups using DMARDs only (group 1) and patients using DMARDs and biologic agents together (group 2). In both groups; Schirmer's II test, tear film break-up time (tBUT), central corneal thickness (CCT), corneal volume (CV), intraocular pressure (IOP) measurement, and anterior segment and fundus examinations of the eye with slit lamp were carried out. Ocular surface disease index (OSDI) score questionnaire were performed. RESULTS: Thirty-eight patients with a mean age of 53.00 +/- 8.19 years were in group 1 and 18 patients with a mean age of 51.00 +/- 9.54 years were in group 2. The mean duration of RA was 6.89 +/- 7.96 years in group 1 and 5.70 +/- 9.00 years in group 2. There was a statistically significant difference between two groups with tBUT, CCT, CV, IOP (p < 0.05) and there was no significant difference with age, sex, disease duration, disease activity, and Schirmer's II test (p > 0.05). The disease duration showed a significant moderate negative correlation with CCT and CV in group 2 (p < 0.05). CONCLUSIONS: Although tBUT values were significantly higher in the combination treatment group, CCT and CV values were significantly lower. Due to the decrease in corneal thickness, IOP was determined to be significantly lower. PMID- 26878899 TI - Analysis of Iterative Screening with Stepwise Compound Selection Based on Novartis In-house HTS Data. AB - With increased automation and larger compound collections, the development of high-throughput screening (HTS) started replacing previous approaches in drug discovery from around the 1980s onward. However, even today it is not always appropriate, or even feasible, to screen large collections of compounds in a particular assay. Here, we present an efficient method for iterative screening of small subsets of compound libraries. With this method, the retrieval of active compounds is optimized using their structural information and biological activity fingerprints. We validated this approach retrospectively on 34 Novartis in-house HTS assays covering a wide range of assay biology, including cell proliferation, antibacterial activity, gene expression, and phosphorylation. This method was employed to retrieve subsets of compounds for screening, where selected hits from any given round of screening were used as starting points to select chemically and biologically similar compounds for the next iteration. By only screening ~1% of the full screening collection (~15 000 compounds), the method consistently retrieves diverse compounds belonging to the top 0.5% of the most active compounds for the HTS campaign. For most of the assays, over half of the compounds selected by the method were found to be among the 5% most active compounds of the corresponding full-deck HTS. In addition, the stringency of the iterative method can be modified depending on the number of compounds one can afford to screen, making it a flexible tool to discover active compounds efficiently. PMID- 26878900 TI - Novel porphyrin-preparation, characterization, and applications in solar energy conversion. AB - Porphyrins have been demonstrated as one of the most efficient sensitizers in dye sensitized solar cells (DSSC). Herein, we investigated a series of porphyrin sensitizers functionalized with various pi-spacers, such as phenyl for LD14, thiophene for LW4, thiophene-phenyl for LW5, and 2,1,3-benzothiadiazole (BTD) phenyl for LW24. Photo-physical investigation by means of time-resolved fluorescence and nanosecond transient absorption spectroscopy revealed an accelerated inner charge transfer in porphyrins containing the BTD-phenyl pi spacer. Implementation of an auxiliary electron-deficient BTD unit to the porphyrin spacer also results in a broad light-harvesting ability extending up to 840 nm, contributing to an enhanced charge transfer character from the porphyrin ring to the anchoring group. When utilized as a sensitizer in DSSCs, the LW24 device achieved a power conversion efficiency of 9.2%, higher than those based on LD14 or LW5 porphyrins (PCE 9.0% or 8.2%, respectively) but lower than that of the LW4 device (PCE 9.5%). Measurements of transient photovoltage decays demonstrate that the LW24 device features the up-shifted potential band edge of the conduction band of TiO2, but involves serious charge recombination in the dye/TiO2 interface. The findings provide insights into the molecular structure and the charge-transfer characteristics for designing efficient porphyrin sensitizers for DSSC applications. PMID- 26878898 TI - Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival. AB - Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established. PMID- 26878901 TI - In situ plasmonic Ag nanoparticle anchored TiO2 nanotube arrays as visible-light driven photocatalysts for enhanced water splitting. AB - An ultrasonication-assisted in situ deposition strategy was utilised to uniformly decorate plasmonic Ag nanoparticles on vertically aligned TiO2 nanotube arrays (NTAs) to construct a Ag@TiO2 NTA composite. The Ag nanoparticles act as efficient surface plasmon resonance (SPR) photosensitizers to drive photocatalytic water splitting under visible light irradiation. The Ag nanoparticles were uniformly deposited on the surface and inside the highly oriented TiO2 nanotubes. The visible-light-driven hydrogen production activities of silver nanoparticle anchored TiO2 nanotube array photocatalysts were evaluated using methanol as a sacrificial reagent in water under a 500 W Xe lamp with a UV light cutoff filter (lambda >= 420 nm). It was found that the hydrogen production rate of the Ag@TiO2 NTAs prepared with ultrasonication-assisted deposition for 5 min was approximately 15 times higher than that of its pristine TiO2 NTAs counterpart. The highly efficient photocatalytic hydrogen evolution is attributed to the SPR effect of Ag for enhanced visible light absorption and boosting the photogenerated electron-hole separation/transfer. This strategy is promising for the design and construction of high efficiency TiO2 based photocatalysts for solar energy conversion. PMID- 26878903 TI - Total Synthesis of (+/-)-Gracilioether F. AB - Total synthesis of (+/-)-gracilioether F was achieved via a pivotal reductive cleavage of 1,2-dioxane from allenic ester in 11 steps. The key 1,2-dioxane species, derived from singlet oxygen and a diene, could be used as a common precursor for a stereocontrolled formation of the crucial 1,4-diol through a reductive cleavage. PMID- 26878904 TI - Accessibility of summer meals and the food insecurity of low-income households with children. AB - OBJECTIVE: Almost no previous research has examined the impact of the US Department of Agriculture's (USDA) Summer Food Service Program and related Seamless Summer Option, which provide meals and snacks to low-income children over the summer. The present study investigated whether geographic accessibility of summer meals programme sites (a proxy for programme participation) was associated with food insecurity for low-income households. DESIGN: The study used data from the California Health Interview Survey (CHIS) and administrative data on summer meals sites in California. Geocoding was used to calculate driving time between CHIS households and nearby summer meals sites. Geographic accessibility was measured using a gravity model, which accounted for the spatially distributed supply of and demand for summer meals. Food insecurity and very low food security were measured using a standard six-item measure from the USDA. SUBJECTS: Low income families with children (n 5394). SETTING: A representative surveillance study of non-institutionalized households in California. RESULTS: Geographic accessibility was not associated with food insecurity. However, geographic accessibility was associated with a significantly lower probability of very low food security in the full sample and among households with younger children and those living in less urban areas. CONCLUSIONS: The USDA's summer meals programme may be effective at reducing the most severe form of food insecurity for low income households with children. Expanding the number of summer meals sites, the number of meals served at sites and sites' hours of operation may be effective strategies to promote nutritional health over the summer months. PMID- 26878906 TI - A superhydrophobic zeolitic imidazolate framework (ZIF-90) with high steam stability for efficient recovery of bioalcohols. AB - A superhydrophobic zeolitic imidazolate framework (ZIF-90) with high steam stability is prepared through post-functionalization via an amine condensation reaction. The developed superhydrophobic ZIF-90 is highly promising as an effective and reusable adsorbent for bio-alcohol recovery. PMID- 26878905 TI - Rational design of reversible and irreversible cysteine sulfenic acid-targeted linear C-nucleophiles. AB - Concerns about off-target effects has motivated the development of reversible covalent inhibition strategies for targeting cysteine. However, such strategies have not been reported for the unique cysteine oxoform, sulfenic acid. Herein, we have designed and identified linear C-nucleophiles that react selectively with cysteine sulfenic acid. The resulting thioether adducts exhibit reversibility ranging from minutes to days under reducing conditions, showing the feasibility of tuning C-nucleophile reactivity across a wide range of time scales. PMID- 26878907 TI - Quantitative secondary electron imaging for work function extraction at atomic level and layer identification of graphene. AB - Two-dimensional (2D) materials usually have a layer-dependent work function, which require fast and accurate detection for the evaluation of their device performance. A detection technique with high throughput and high spatial resolution has not yet been explored. Using a scanning electron microscope, we have developed and implemented a quantitative analytical technique which allows effective extraction of the work function of graphene. This technique uses the secondary electron contrast and has nanometre-resolved layer information. The measurement of few-layer graphene flakes shows the variation of work function between graphene layers with a precision of less than 10 meV. It is expected that this technique will prove extremely useful for researchers in a broad range of fields due to its revolutionary throughput and accuracy. PMID- 26878908 TI - Regulatory role of hexosamine biosynthetic pathway on hepatic cancer stem cell marker CD133 under low glucose conditions. AB - Cancer was hypothesized to be driven by cancer stem cells (CSCs), but the metabolic determinants of CSC-like phenotype still remain elusive. Here, we present that hexosamine biosynthetic pathway (HBP) at least in part rescues cancer cell fate with inactivation of glycolysis. Firstly, metabolomic analysis profiled cellular metabolome in CSCs of hepatocellular carcinoma using CD133 cell surface marker. The metabolic signatures of CD133-positive subpopulation compared to CD133-negative cells highlighted HBP as one of the distinct metabolic pathways, prompting us to uncover the role of HBP in maintenance of CSC-like phenotype. To address this, CSC-like phenotypes and cell survival were investigated in cancer cells under low glucose conditions. As a result, HBP inhibitor azaserine reduced CD133-positive subpopulation and CD133 expression under high glucose condition. Furthermore, treatment of N-Acetylglucosamine in part restores CD133-positive subpopulation when either 2.5 mM glucose in culture media or glycolytic inhibitor 2-deoxy-D-glucose in HCC cell lines was applied, enhancing CD133 expression as well as promoting cancer cell survival. Together, HBP might be a key metabolic determinant in the functions of hepatic CSC marker CD133. PMID- 26878909 TI - Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium. AB - Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis. PMID- 26878910 TI - "Optical communication with brain cells by means of an implanted duplex micro device with optogenetics and Ca(2+) fluoroimaging". AB - To better understand the brain function based on neural activity, a minimally invasive analysis technology in a freely moving animal is necessary. Such technology would provide new knowledge in neuroscience and contribute to regenerative medical techniques and prosthetics care. An application that combines optogenetics for voluntarily stimulating nerves, imaging to visualize neural activity, and a wearable micro-instrument for implantation into the brain could meet the abovementioned demand. To this end, a micro-device that can be applied to the brain less invasively and a system for controlling the device has been newly developed in this study. Since the novel implantable device has dual LEDs and a CMOS image sensor, photostimulation and fluorescence imaging can be performed simultaneously. The device enables bidirectional communication with the brain by means of light. In the present study, the device was evaluated in an in vitro experiment using a new on-chip 3D neuroculture with an extracellular matrix gel and an in vivo experiment involving regenerative medical transplantation and gene delivery to the brain by using both photosensitive channel and fluorescent Ca(2+) indicator. The device succeeded in activating cells locally by selective photostimulation, and the physiological Ca(2+) dynamics of neural cells were visualized simultaneously by fluorescence imaging. PMID- 26878911 TI - Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress. AB - Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown. In this study, we demonstrated that SiO2 NP induced the expression of follistatin (FST), a stress responsive gene, in mouse lung tissue as well as in human lung epithelial cells (A549). The levels of Ac-H3(K9/18) and H3K4me2, two active gene markers, at FST promoter region were significantly increased during SiO2 NP treatment. The induction of FST transcription was mediated by the nuclear factor erythroid 2 related factor 2 (Nrf2), as evidenced by the decreased FST expression in Nrf2 deficient cells and the direct binding of Nrf2 to FST promoter region. Down regulation of FST promoted SiO2 NP-induced apoptosis both in cultured cells and in mouse lung tissue. Furthermore, knockdown of FST increased while overexpression of FST decreased the expression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxygen species (ROS). Taken together, these findings demonstrated a protective role of FST in SiO2 NP induced oxidative stress and shed light on the interaction between SiO2 NPs and biological systems. PMID- 26878915 TI - Editorial. PMID- 26878912 TI - Knockout of BRD7 results in impaired spermatogenesis and male infertility. AB - BRD7 was originally identified as a novel bromodomain gene and a potential transcriptional factor. BRD7 was found to be extensively expressed in multiple mouse tissues but was highly expressed in the testis. Furthermore, BRD7 was located in germ cells during multiple stages of spermatogenesis, ranging from the pachytene to the round spermatid stage. Homozygous knockout of BRD7 (BRD7(-/-)) resulted in complete male infertility and spermatogenesis defects, including deformed acrosomal formation, degenerative elongating spermatids and irregular head morphology in postmeiotic germ cells in the seminiferous epithelium, which led to the complete arrest of spermatogenesis at step 13. Moreover, a high ratio of apoptosis was determined by TUNEL analysis, which was supported by high levels of the apoptosis markers annexin V and p53 in knockout testes. Increased expression of the DNA damage maker lambdaH2AX was also found in BRD7(-/-) mice, whereas DNA damage repair genes were down-regulated. Furthermore, no or lower expression of BRD7 was detected in the testes of azoospermia patients exhibiting spermatogenesis arrest than that in control group. These data demonstrate that BRD7 is involved in male infertility and spermatogenesis in mice, and BRD7 defect might be associated with the occurrence and development of human azoospermia. PMID- 26878913 TI - Albuminuria, Cerebrovascular Disease and Cortical Atrophy: among Cognitively Normal Elderly Individuals. AB - We tested the hypothesis that decreased glomerular filtration rate and albuminuria have different roles in brain structure alterations. We enrolled 1,215 cognitively normal individuals, all of whom underwent high-resolution T1 weighted volumetric magnetic resonance imaging scans. The cerebral small vessel disease burdens were assessed with white matter hyperintensities (WMH), lacunes, and microbleeds. Subjects were considered to have an abnormally elevated urine albumin creatinine ratio if the value was >=17 mg/g for men and >=25 mg/g for women. Albuminuria, but not estimated glomerular filtration rate (eGFR), was associated with increased WMH burdens (p = 0.002). The data was analyzed after adjusting for age, sex, education, history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, total cholesterol level, body mass index, status of smoking and alcohol drinking, and intracranial volume. Albuminuria was also associated with cortical thinning, predominantly in the frontal and occipital regions (both p < 0.01) in multiple linear regression analysis. However, eGFR was not associated with cortical thickness. Furthermore, path analysis for cortical thickness showed that albuminuria was associated with frontal thinning partially mediated by WMH burdens. The assessment of albuminuria is needed to improve our ability to identify individuals with high risk for cognitive impairments, and further institute appropriate preventive measures. PMID- 26878914 TI - Identification of a Vibrio cholerae chemoreceptor that senses taurine and amino acids as attractants. AB - Vibrio cholerae, the etiological agent of cholera, was found to be attracted by taurine (2-aminoethanesulfonic acid), a major constituent of human bile. Mlp37, the closest homolog of the previously identified amino acid chemoreceptor Mlp24, was found to mediate taxis to taurine as well as L-serine, L-alanine, L-arginine, and other amino acids. Methylation of Mlp37 was enhanced upon the addition of taurine and amino acids. Isothermal titration calorimetry demonstrated that a purified periplasmic fragment of Mlp37 binds directly to taurine, L-serine, L alanine and L-arginine. Crystal structures of the periplamic domain of Mlp37 revealed that L-serine and taurine bind to the membrane-distal PAS domain in essentially in the same way. The structural information was supported by characterising the in vivo properties of alanine-substituted mutant forms of Mlp37. The fact that the ligand-binding domain of the L-serine complex had a small opening, which would accommodate a larger R group, accounts for the broad ligand specificity of Mlp37 and allowed us to visualise ligand binding to Mlp37 with fluorescently labelled L-serine. Taken together, we conclude that Mlp37 serves as the major chemoreceptor for taurine and various amino acids. PMID- 26878916 TI - Effectiveness of the interventions in preventing the progression of pre-frailty and frailty in older adults: a systematic review protocol. PMID- 26878917 TI - Efficacy and safety of pancreatic enzyme replacement therapy in pancreatic exocrine insufficiency: a systematic review protocol. PMID- 26878918 TI - Risk factors for and characteristics of dysphagia development in thermal burn injury and/or inhalation injury patients: a systematic review protocol. PMID- 26878919 TI - Caregiver experiences of providing care to adult individuals living with a left ventricular assist device: a qualitative systematic review protocol. PMID- 26878921 TI - Effectiveness of decision tools used to identify adult patients suitable for early discharge from emergency departments: a systematic review protocol. PMID- 26878920 TI - The effect of yoga on depression and pain in adult patients with chronic low back pain: a systematic review protocol. PMID- 26878922 TI - The experiences of stroke survivors, their families and unpaid carers regarding goal setting within stroke rehabilitation: a systematic review protocol. PMID- 26878923 TI - Parents' and carers' experiences of transitions and aftercare following a child's discharge from a pediatric intensive care unit to an inpatient ward setting: a qualitative systematic review protocol. PMID- 26878924 TI - The experiences of mental health professionals and patients in the use of pro re nata medication in acute adult mental health care settings: a systematic review protocol of qualitative evidence. PMID- 26878925 TI - The effectiveness of structured interdisciplinary collaboration for adult home hospice patients on patient satisfaction and hospital admissions and re admissions: a systematic review. AB - BACKGROUND: Patient satisfaction and hospital re-admission rates are the two major outcomes for measuring quality of healthcare delivery. Interdisciplinary collaboration, a concept that describes coordination of care between multiple healthcare professionals and patients and families to deliver the highest quality of care across settings, is fundamental to improving patient outcomes. Home hospice care is palliative in nature and is a critical segment of patient care. To date, no systematic review has been undertaken to determine the effectiveness of structured interdisciplinary collaboration in the home hospice setting in relation to patient satisfaction and hospital readmission. OBJECTIVE: The aim of the review was to synthesize the best available evidence on the effectiveness of structured interdisciplinary collaboration on patient satisfaction and hospital admission and re-admission rates for adults receiving home hospice services. INCLUSION CRITERIA: Adults, male and female (18 years old or older), receiving home hospice services or transitioning from hospital to home hospice servicesThe studies that evaluate interdisciplinary collaboration among the hospice team providing home hospice services in the home care settingsIn this review, randomized controlled trials and quasi-experimental studies were considered for inclusion.Patient satisfaction and all cause hospital admissions and re-admission rates. SEARCH STRATEGY: Published and unpublished literature in the English language was sought from the inception of the databases through August 15, 2014. The databases searched included: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Nursing & Allied Health Source, Health Source: Nursing/Academic Edition and ProQuest Health Management. A search of grey literature and any relevant homecare/hospice websites was also performed. RESULTS: There were no studies located that met the inclusion requirements of this review. There were no text or opinion pieces that were specific to structured interdisciplinary collaboration among the hospice team in home care settings on patient satisfaction and hospital readmission. CONCLUSION: There is currently no evidence available to determine the effectiveness of structured interdisciplinary collaboration among hospice teams in home care settings in regard to patient satisfaction and hospital readmission. IMPLICATIONS FOR PRACTICE: No conclusive recommendations can be made regarding the effectiveness of structured interdisciplinary collaboration among home hospice teams in home care settings in regard to patient satisfaction and hospital readmission. IMPLICATIONS FOR RESEARCH: Quantitative and qualitative research studies are urgently required to determine the effectiveness of structured interdisciplinary collaboration among home hospice teams in home care settings in regard to patient satisfaction and hospital readmission. PMID- 26878926 TI - The effectiveness of systematic perioperative oral hygiene in reduction of postoperative respiratory tract infections after elective thoracic surgery in adults: a systematic review. AB - BACKGROUND: Nosocomial infections are a significant contributor to patient morbidity and mortality. Nosocomial infections significantly increase hospital length of stay and total hospital costs. Thoracic surgery, mechanical ventilation and/or admission to an intensive care unit are known to increase patients' risk for nosocomial respiratory tract infection. OBJECTIVES: To identify, appraise and synthesize the best available evidence on the effectiveness of systematic perioperative oral hygiene in the reduction of postoperative respiratory airway infections in adult patients undergoing elective thoracic surgery. INCLUSION CRITERIA: Patients over the age of 18 years who had been admitted for elective thoracic surgery, regardless of gender, ethnicity, diagnosis severity, co morbidity or previous treatment.Perioperative systematic oral hygiene (such as mechanical removal of dental biofilm or plaques and/or systematic use of mouth rinse) performed by patients themselves or by healthcare staff (such as nurses).Randomized controlled trials and quasi-experimental studies.Nosocomial infections, specifically respiratory tracts infections, and surgical site infections SEARCH STRATEGY: Multiple databases (PubMed, CINAHL, Embase, Scopus, Swemed+, Health Technology Assessment Database and Turning Research Into Practice [TRIP] database) were searched from 1980 to December 2014. Studies published in English, German, Danish, Swedish and Norwegian were considered for inclusion in this review. METHODOLOGICAL QUALITY: Two independent reviewers used the standard critical appraisal tool from the Joanna Briggs Institute to assess the methodological quality of studies. DATA EXTRACTION: The process of data extraction was undertaken independently by two reviewers using tools from the Joanna Briggs Institute. DATA SYNTHESIS: Quantitative results were synthesized in meta-analysis. RESULTS: This review includes six studies: three randomized controlled trials and three quasi-experimental studies.The absolute magnitude of the summary effect sizes were: for nosocomial infections relative risk (RR) 0.65 (95% confidence interval [CI] 0.55-0.78) for respiratory tract infections RR 0.48 (95%CI: 0.36-0.65) and for deep surgical site infections RR 0.48 (95%CI 0.27 0.84). CONCLUSIONS: Systematic perioperative oral hygiene reduces postoperative nosocomial, lower respiratory tract infections and surgical site infections but not urinary tract infections. The effect is statistically, clinically and practically significant.Perioperative decontamination of the nasopharynx and/or oropharynx is a strategy worth pursuing. The intervention is cheap and can easily be carried out by the patients themselves. (Grade A)Studies testing decontamination of the nasopharynx and/or oropharynx have until now only included patients undergoing thoracic surgical procedures. As the interventions are cheap, easy to carry out and have a great impact on the patients' outcome, it is recommendable to carry out more studies involving other type of patients undergoing major surgery with a high prevalence of nosocomial infections, respiratory tract infections and surgical site infections. PMID- 26878927 TI - The effectiveness of inpatient physical therapy compared to outpatient physical therapy in older adults after total hip replacement in the post-discharge period: a systematic review. AB - BACKGROUND: Total hip replacement is the most effective and safest method for treating severe degenerative, traumatic and other diseases of the hip joint. Total hip replacement can reliably relieve pain and improve function in the majority of patients for a period of 15 to 20 years or more postoperatively. Physical therapy follows each total hip replacement surgery. Physical therapy protocols after total hip replacement in the post-discharge period vary widely in terms of setting (inpatient, outpatient), content (the particular set of exercises used), and frequency (e.g. daily versus twice a week). In current literature, there is no systematic review which has compared the effectiveness of inpatient and outpatient physical therapy in patients after total hip replacement in the post-discharge period. OBJECTIVES: The objective of this systematic review was to compare the effectiveness of inpatient physical therapy with outpatient physical therapy on the quality of life and gait measures in older adults after total hip replacement in the post-discharge period. INCLUSION CRITERIA: This review considered studies that include older adults (over 65 years) who have had total hip replacement and are in the post-discharge period. Adults with bilateral or multiple simultaneous surgeries and also patients who have had hemiarthroplasty of the hip joint were excluded.This review considered studies that included any type of physical therapy delivered in inpatient settings provided by professionals with education in physical therapy. Inpatient physical therapy delivered at any frequency and over any duration was included.This review considered studies that included as a comparator any type of physical therapy delivered in outpatient settings provided by professionals with education in physical therapy or no physical therapy.This review considered studies that included the following primary and secondary outcomes. The primary outcome was quality of life, assessed by any validated assessment tool. The secondary outcome was measures of gait assessed by any valid methods.This review considered both experimental and observational study designs including randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies and analytical cross sectional studies for inclusion. SEARCH STRATEGY: The search strategy aimed to find both published and unpublished studies. A three-step search strategy was utilized in 12 databases. Studies published in all languages and any date were considered for inclusion in this review. METHODOLOGICAL QUALITY: Assessment of methodological quality was not conducted as no studies were identified that met the inclusion criteria. DATA EXTRACTION AND SYNTHESIS: Data extraction and synthesis was not performed because no studies were included in this systematic review. RESULTS: During to the three-step search strategy 4330 papers were identified. The primary and secondary reviewer independently retrieved 42 potentially relevant papers according to the inclusion criteria by title and abstract screening. Following assessment of full text all of the retrieved papers were excluded based on the inclusion criteria. CONCLUSIONS: There is no scientific evidence comparing the effectiveness of inpatient physical therapy with outpatient physical therapy in older patients after total hip replacement in the post-discharge period. IMPLICATIONS FOR RESEARCH: This systematic review has identified gaps in the literature for comparing the effectiveness of inpatient physical therapy with and outpatient physical therapy on the quality of life and gait measures in older adults after total hip replacement in the post-discharge period. Prospective randomized double blind multicenter controlled trials are needed to answer this important clinical question. PMID- 26878928 TI - The effectiveness of the teach-back method on adherence and self-management in health education for people with chronic disease: a systematic review. AB - BACKGROUND: Chronic diseases are increasing worldwide and have become a significant burden to those affected by those diseases. Disease-specific education programs have demonstrated improved outcomes, although people do forget information quickly or memorize it incorrectly. The teach-back method was introduced in an attempt to reinforce education to patients. To date, the evidence regarding the effectiveness of health education employing the teach-back method in improved care has not yet been reviewed systematically. OBJECTIVES: This systematic review examined the evidence on using the teach-back method in health education programs for improving adherence and self-management of people with chronic disease. INCLUSION CRITERIA: Adults aged 18 years and over with one or more than one chronic disease.All types of interventions which included the teach-back method in an education program for people with chronic diseases. The comparator was chronic disease education programs that did not involve the teach back method.Randomized and non-randomized controlled trials, cohort studies, before-after studies and case-control studies.The outcomes of interest were adherence, self-management, disease-specific knowledge, readmission, knowledge retention, self-efficacy and quality of life. SEARCH STRATEGY: Searches were conducted in CINAHL, MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, ProQuest Nursing and Allied Health Source, and Google Scholar databases. Search terms were combined by AND or OR in search strings. Reference lists of included articles were also searched for further potential references. METHODOLOGICAL QUALITY: Two reviewers conducted quality appraisal of papers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. DATA EXTRACTION: Data were extracted using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument data extraction instruments. DATA SYNTHESIS: There was significant heterogeneity in selected studies, hence a meta-analysis was not possible and the results were presented in narrative form. RESULTS: Of the 21 articles retrieved in full, 12 on the use of the teach-back method met the inclusion criteria and were selected for analysis. Four studies confirmed improved disease-specific knowledge in intervention participants. One study showed a statistically significant improvement in adherence to medication and diet among type 2 diabetics patients in the intervention group compared to the control group (p < 0.001). Two studies found statistically significant improvements in self-efficacy (p = 0.0026 and p < 0.001) in the intervention groups. One study examined quality of life in heart failure patients but the results did not improve from the intervention (p = 0.59). Five studies found a reduction in readmission rates and hospitalization but these were not always statistically significant. Two studies showed improvement in daily weighing among heart failure participants, and in adherence to diet, exercise and foot care among those with type 2 diabetes. CONCLUSIONS: Overall, the teach-back method showed positive effects in a wide range of health care outcomes although these were not always statistically significant. Studies in this systematic review revealed improved outcomes in disease-specific knowledge, adherence, self efficacy and the inhaler technique. There was a positive but inconsistent trend also seen in improved self-care and reduction of hospital readmission rates. There was limited evidence on improvement in quality of life or disease related knowledge retention.Evidence from the systematic review supports the use of the teach-back method in educating people with chronic disease to maximize their disease understanding and promote knowledge, adherence, self-efficacy and self care skills.Future studies are required to strengthen the evidence on effects of the teach-back method. Larger randomized controlled trials will be needed to determine the effectiveness of the teach-back method in quality of life, reduction of readmission, and hospitalizations. PMID- 26878929 TI - Purposeful and timely nursing rounds: a best practice implementation project. AB - BACKGROUND: Purposeful and timely rounding is a best practice intervention to routinely meet patient care needs, ensure patient safety, decrease the occurrence of patient preventable events, and proactively address problems before they occur. The Institute for Healthcare Improvement (IHI) endorsed hourly rounding as the best way to reduce call lights and fall injuries, and increase both quality of care and patient satisfaction. Nurse knowledge regarding purposeful rounding and infrastructure supporting timeliness are essential components for consistency with this patient centred practice. OBJECTIVES: The project aimed to improve patient satisfaction and safety through implementation of purposeful and timely nursing rounds. Goals for patient satisfaction scores and fall volume were set. Specific objectives were to determine current compliance with evidence-based criteria related to rounding times and protocols, improve best practice knowledge among staff nurses, and increase compliance with these criteria. METHODS: For the objectives of this project the Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice audit tool were used. Direct observation of staff nurses on a medical surgical unit in the United States was employed to assess timeliness and utilization of a protocol when rounding. Interventions were developed in response to baseline audit results. A follow-up audit was conducted to determine compliance with the same criteria. For the project aims, pre- and post-intervention unit-level data related to nursing sensitive elements of patient satisfaction and safety were compared. RESULTS: Rounding frequency at specified intervals during awake and sleeping hours nearly doubled. Use of a rounding protocol increased substantially to 64% compliance from zero. Three elements of patient satisfaction had substantive rate increases but the hospital's goals were not reached. Nurse communication and pain management scores increased modestly (5% and 11%, respectively). Responsiveness of hospital staff increased moderately (15%) with a significant sub-element increase in toileting (41%). Patient falls decreased by 50%. CONCLUSIONS: Nurses have the ability to improve patient satisfaction and patient safety outcomes by utilizing nursing round interventions which serve to improve patient communication and staff responsiveness. Having a supportive infrastructure and an organized approach, encompassing all levels of staff, to meet patient needs during their hospital stay was a key factor for success. Hard-wiring of new practices related to workflow takes time as staff embrace change and understand how best practice interventions significantly improve patient outcomes. PMID- 26878930 TI - Evaluation of the acute changes in objective accommodation, pupil size and ocular wavefront aberrations after cigarette smoking. AB - CONTEXT: The acute effects of cigarette smoking on pupil size and ocular wavefront aberrations (OWA) have been previously documented. The accommodation status of the eye is well known to be related to ocular aberrations. No previous study has evaluated the impact of cigarette smoking on the accommodation status of the eye. This study presents intriguing findings regarding the changes in objective accommodation of the eye after cigarette smoking. OBJECTIVE: To evaluate the acute changes in objective accommodation and OWA after cigarette smoking. MATERIALS AND METHODS: A total of 34 otherwise healthy cigarette smoker participants were included in this prospective study. All subjects smoked a single cigarette containing 1 mg nicotine. Measurements of pupil size, OWA and objective accommodation were done before and after smoking. A Wavefront Aberrometer device (Irx3, Imagine Eyes, Orsay, France) was used for the measurements. RESULTS: The mean age of the participants was 36.6 +/- 10.3 years (range 21-51 years). Pupil size did not significantly differ before (mean 5.72 +/ 1.21 mm) and after smoking (mean 5.68 +/- 1.14 mm) (p = 0.62). However, a significant decrease was observed in total spherical aberration (TSA) of the eye after smoking (p = 0.01). There was an increase in objective accommodation after smoking at each accommodative stimulus (range 0-5). This increment was significant at 2 D (p = 0.02) and 3 D (p = 0.03) of stimulus. DISCUSSION AND CONCLUSIONS: The TSA of the eye significantly decreases after smoking. Cigarette smoking also causes a significant increase in objective accommodation at 2 D and 3 D of stimulus. PMID- 26878931 TI - The potential of peer social norms to shape food intake in adolescents and young adults: a systematic review of effects and moderators. AB - This systematic review aims to assess the role that peer social norms play in shaping young people's food intake, focusing on the important questions of for whom and when peer social norms are related to how much young people eat. Thirty three eligible studies were reviewed (17 correlational, 16 experimental). All but one correlational studies found significant associations between norms and food intake. All experimental studies found effects of norm manipulations on food intake, and some evidence was found of behavioural spillover effects of norms. Four moderators were distilled from our literature synthesis that stipulate for whom and when peer social norms are related to food intake: identification with the norm referent group and eating-related habit strength were found to moderate the effects of social norms on food intake; forceful injunctive norms were found not to be related to food intake; and the influence of norms seemed restricted to types of foods typically consumed in the presence of peers. The findings from this literature synthesis have important implications for research, and moderators are discussed in light of psychological theory. Where applicable, potential implications for the development of social norm-based interventions to improve young people's food intake are also highlighted. PMID- 26878932 TI - Industry and Occupation in the Electronic Health Record: An Investigation of the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System. AB - BACKGROUND: Inclusion of information about a patient's work, industry, and occupation, in the electronic health record (EHR) could facilitate occupational health surveillance, better health outcomes, prevention activities, and identification of workers' compensation cases. The US National Institute for Occupational Safety and Health (NIOSH) has developed an autocoding system for "industry" and "occupation" based on 1990 Bureau of Census codes; its effectiveness requires evaluation in conjunction with promoting the mandatory addition of these variables to the EHR. OBJECTIVE: The objective of the study was to evaluate the intercoder reliability of NIOSH's Industry and Occupation Computerized Coding System (NIOCCS) when applied to data collected in a community survey conducted under the Affordable Care Act; to determine the proportion of records that are autocoded using NIOCCS. METHODS: Standard Occupational Classification (SOC) codes are used by several federal agencies in databases that capture demographic, employment, and health information to harmonize variables related to work activities among these data sources. There are 359 industry and occupation responses that were hand coded by 2 investigators, who came to a consensus on every code. The same variables were autocoded using NIOCCS at the high and moderate criteria level. RESULTS: Kappa was .84 for agreement between hand coders and between the hand coder consensus code versus NIOCCS high confidence level codes for the first 2 digits of the SOC code. For 4 digits, NIOCCS coding versus investigator coding ranged from kappa=.56 to .70. In this study, NIOCCS was able to achieve production rates (ie, to autocode) 31%-36% of entered variables at the "high confidence" level and 49%-58% at the "medium confidence" level. Autocoding (production) rates are somewhat lower than those reported by NIOSH. Agreement between manually coded and autocoded data are "substantial" at the 2-digit level, but only "fair" to "good" at the 4-digit level. CONCLUSIONS: This work serves as a baseline for performance of NIOCCS by investigators in the field. Further field testing will clarify NIOCCS effectiveness in terms of ability to assign codes and coding accuracy and will clarify its value as inclusion of these occupational variables in the EHR is promoted. PMID- 26878933 TI - The immortal amoeba: a useful model to study cellular differentiation processes? PMID- 26878934 TI - Bacterial genomic epidemiology, from local outbreak characterization to species history reconstruction. AB - Bacteriology has embraced the next-generation sequencing revolution, swiftly moving from the time of single genome sequencing to the age of genomic epidemiology. Hundreds and now even thousands of genomes are being sequenced for single bacterial species, allowing unprecedented levels of resolution and insight in the evolution and epidemic diffusion of the main bacterial pathogens. Here, we present a review of some of the most recent and groundbreaking studies in this field. PMID- 26878936 TI - Lupeol Isolated from Sorbus commixta Suppresses 1alpha,25-(OH)2D3-Mediated Osteoclast Differentiation and Bone Loss in Vitro and in Vivo. AB - Lupeol is a lupane-type triterpene isolated from Sorbus commixta, an oriental medicine used to treat arthritis and inflammatory diseases. However, the antiosteoporotic effects of S. commixta or any of its constituents have not been studied yet. In the present study, we have examined the effect of lupeol (a major active triterpenoid isolated from S. commixta) on osteoclastogenesis and sought to elucidate its underlying molecular mechanisms. We evaluated whether lupeol antagonized osteoclast differentiation and bone resorption. Lupeol markedly inhibited osteoclast differentiation and bone resorption activity through its effects on MAP kinases and transcription factors (NF-kappaB, NFATc1, and c-Fos) downstream of the osteoclast differentiation factor receptor RANK. Furthermore, in vivo efficacy of lupeol was confirmed by using an animal model of hypercalcemic mediated bone loss. Taken together, lupeol showed strong inhibitory effects on osteoclastogenesis. Supplementation with S. commixta and lupeol could be beneficial for bone health or osteoclast-related diseases such as osteoporosis, Paget's disease, osteolysis associated with periodontal disease, and multiple myeloma. PMID- 26878937 TI - Visible Light-Controlled Nitric Oxide Release from Hindered Nitrobenzene Derivatives for Specific Modulation of Mitochondrial Dynamics. AB - Nitric oxide (NO) is a physiological signaling molecule, whose biological production is precisely regulated at the subcellular level. Here, we describe the design, synthesis, and evaluation of novel mitochondria-targeted NO releasers, Rol-DNB-mor and Rol-DNB-pyr, that are photocontrollable not only in the UV wavelength range but also in the biologically favorable visible wavelength range (530-590 nm). These caged NO compounds consist of a hindered nitrobenzene as the NO-releasing moiety and a rhodamine chromophore. Their NO-release properties were characterized by an electron spin resonance (ESR) spin trapping method and fluorometric analysis using NO probes, and their mitochondrial localization in live cells was confirmed by costaining. Furthermore, we demonstrated visible light control of mitochondrial fragmentation via activation of dynamin-related protein 1 (Drp1) by means of precisely controlled NO delivery into mitochondria of cultured HEK293 cells, utilizing Rol-DNB-pyr. PMID- 26878938 TI - Rhodium-Catalyzed/Copper-Mediated Tandem C(sp(2))-H Alkynylation and Annulation: Synthesis of 11-Acylated Imidazo[1,2-a:3,4-a']dipyridin-5-ium-4-olates from 2H [1,2'-Bipyridin]-2-ones and Propargyl Alcohols. AB - A rhodium-catalyzed/copper-mediated tandem C(sp(2))-H alkynylation and intramolecular annulation of 2H-[1,2'-bipyridin]-2-ones with propargyl alcohols for the synthesis of 11-acylated imidazo[1,2-a:3,4-a']dipyridin-5-ium-4-olates is described. PMID- 26878935 TI - Presence of Wuchereria bancrofti microfilaremia despite 7 years of annual ivermectin monotherapy mass drug administration for onchocerciasis control: a study in north-west Ethiopia. AB - BACKGROUND: There is considerable interest in determining whether mass drug administration (MDA) with ivermectin for onchocerciasis control will eliminate coendemic lymphatic filariasis (LF). The objective of this study was to determine the prevalence of LF microfilaremia in onchocerciasis endemic districts that had received 7 years of MDA with ivermectin. METHOD: Three villages with a 2010 LF circulating antigenaemia prevalence (determined in a mapping exercise using immunochromatography tests) ranging from 23 to 56% were surveyed for the presence of Wuchereria bancrofti microfilaria (mf) in 2012. These villages had been treated with ivermectin MDA for onchocerciasis with reported total population coverage of >=65%. A total of 774 residents aged 2 years and above, of both genders, provided 60 MUl nocturnal blood samples between 10 pm and 2 am. Standard thick smears were prepared and examined microscopically after Giemsa staining for the presence of W. bancrofti mf. RESULTS: The mean mf prevalence was 4.7% (village range 1.1-11.0%). The mean mf density was 9.8 mf/60 MUl (village range 9 13.1) among the positive individuals. Children in the 2-4-year-old and 5-9-year old age groups were infected suggesting transmission occurred during the MDA period. A village level review of MDA treatment coverage records showed an average total population coverage of 66.4% over a 7-year period, but with a considerable range of annual coverage (43.0-89.9%). In addition, village level treatment coverage data were missing from the village with the highest mf prevalence (11%) for 2 of the 7 years. CONCLUSION: 7 years of annual mass treatment with ivermectin monotherapy for onchocerciasis did not interrupt LF transmission. In expanding the onchocerciasis ivermectin MDA programme to include LF, albendazole should be added and treatment coverage improved. PMID- 26878939 TI - Early intervention in psychosis: Perspectives on Asian studies. PMID- 26878940 TI - Brain stimulation therapies for psychiatric disorders: The first decade of the new millennium--A review. AB - Three new brain stimulation therapies have emerged in the last decade for clinical use in psychiatric disorders. Combined with electroconvulsive therapy (ECT), these therapies offer much hope to patients with medication refractory depression, obsessive-compulsive disorder and auditory hallucinations of schizophrenia. In this article we briefly review the history, development and evidence for each of the four stimulation therapies and describe the current state-of-the-art. Neuromodulation is considered as a possible common mechanism mediating the effects of these therapies. Finally, empirical guidelines are suggested for the practicing psychiatrist for the optimal utilization of stimulation therapies. It is concluded that with increasing technological sophistication, research on optimal protocols and emergence of newer modalities of stimulation, the future holds much promise for neuromodulatory therapies in psychiatric disorders. PMID- 26878941 TI - Electroconvulsive therapy (ECT) in bipolar disorder: A narrative review of literature. AB - In many countries including India electroconvulsive therapy (ECT) is frequently used to treat different phases of bipolar disorder. The response to ECT is impressive in mania, depression and in mixed affective states. Preliminary evidence also suggests benefit from maintenance ECT in bipolar disorder. However, most of the literature on efficacy and adverse effects comes from case series, retrospective reports and open trials - controlled trials have been few and far between. Official guidelines recommend the use of ECT only when there is a dire emergency or when all other options have been exhausted. Concurrent use of lithium and antiepileptic drugs along with ECT is common in clinical practice. While such practice appears to be largely safe, one should be mindful about dose of lithium and possible interference of antiepileptic drugs with efficacy of ECT. The use of suprathreshold bilateral ECT and bifrontal placement of electrodes may confer some advantage over other methods. PMID- 26878942 TI - Ethnopsychopharmacology considerations for Asians and Asian Americans. AB - Asians comprise more than 60% of the world's population and are the fastest growing minority group in the United States. Today's psychiatrist must learn to recognize and appreciate the unique factors that influence mental health outcomes in this group. Asian Americans are affected by psychiatric disorders at similar rates as non-Asians, but are significantly underrepresented in psychiatric clinics. When Asians and Asian Americans do present for psychiatric treatment, they often do so with higher severity of illness, and variable levels of compliance. Studies over the past three decades have suggested that pharmacokinetic and pharmacodynamic profiles of various psychotropic medications may be different in Asians, leading to differences in dosage requirements and side-effect profiles. These variations appear to be largely determined by genetic predisposition, but are also influenced by other factors such as environment, social support, cultural perceptions, and physicians' prescribing habits. In this paper, we provide an overview of biological and socio-cultural issues as they relate to psychopharmacology in Asians and Asian Americans, with the hope that a better understanding of these issues will lead to improved mental health care delivery to this population both in the United States, as well as in Asian countries. PMID- 26878944 TI - Barriers to discharge of patients from a government-run day-care psychiatric rehabilitation center in India. AB - OBJECTIVE: Many psychiatric patients undergoing vocational training do not achieve successful transition to regular work. In this study, we evaluated the barriers for discharge from day care center to actual work place. MATERIALS AND METHODS: In a cross-sectional study at a government-run day-care center at National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, we studied 76 patients who were undergoing vocational training for more than 1 year. We did a semi-structured interview with patients, their family members, and instructors of various occupational sections. We used a questionnaire of 17 different barriers to assess the obstacles in their discharge from day-care center to actual work place. RESULTS: The majority of them had a diagnosis of mental retardation (n=47) followed by schizophrenia (n=29), and bipolar disorder (n=9). The mean (SD) age and duration of illness was 33.6 (9.7) years and 12.5 (9.3) years, respectively. Patients had more than one diagnosis. The median duration of stay in day-care center was 5.9 years. Doubts regarding performance at a new work place (n=60), fear of performance at new work place (n=65), and the fear of transition to regular work (n=64) were the most common barriers reported by patients, their family members and instructors of various occupational sections, respectively. DISCUSSION: Educating patients and their family members, gradual exposure to new working environment, and increased community level vocational opportunities may potentially overcome above barriers. Getting them to the actual job early in their course of treatment will improve their adjustment to a new work place and overall outcome. PMID- 26878943 TI - Family violence influences mental health of school girls in Iran: Results of a preliminary study. AB - INTRODUCTION: The family plays the first and may be the most important role in the development of individuals' personality, health and function. The current study aimed to evaluate different aspects of violence against a sample of school girls of Iranian population and its effect on their mental health. METHODS: A cluster, randomized sample consisting of 399 school girls was selected from all of the high schools in Tabriz city, northwest of Iran. Students were asked to participate in this study anonymously. Signs and symptoms of depression and anxiety were assessed by the General health questionnaire-28 (GHQ-28) measuring their social function and physical situation as well. Another inquiry form involving questions about different kinds of violence and neglect gathered information about their situation during the recent year. RESULTS: The mean (SD) age of the students was 14.9 (0.8) and all were under 18. The mean (SD) total score of GHQ-28 was 24.18(13.61). The sub-threshold score in GHQ-28 (under 23) was observed in 44.1% of students which indicates considerable problems in mental health status. The type of reported violence was not significantly associated with an abnormal score of GHQ-28. A higher score of somatic symptoms was related to verbal violence at home by parents and the educational level of mother. High score on social dysfunction was predicted by lower educational level of mother. The depression scale was related to humility, neglect and discrimination at home. The factors were not predicting the score of anxiety or insomnia subscales. DISCUSSION: The current study observed a noticeable amount of problems in the mental health of teenage girls in a sample of the Iranian population. The educational level of the mother plays an important role in the mental health of school girls. PMID- 26878945 TI - Validation of Malaysian translated distress thermometer with problem checklist among the breast cancer survivors in Malaysia. AB - INTRODUCTION: Distress thermometer (DT) is a single-item measure generated to assess the psychological distress among cancer patients. The aim of this study was to validate the translated DT as a tool to determine the psychological distress level and assess the factors associated with distress among the working breast cancer survivors and also to compare with the Hospital Anxiety and Depression Scale (HADS). METHODS: 150 working breast cancer survivors were interviewed using the Malay and Chinese language translated version of DT and HADS. RESULTS: Based on HADS, 23.3% were anxious, 19.3% were depressed whereas 15.3% experienced both anxiety and depression. About 14.7% of the respondents reported distress (cutoff>=5) on DT. A significant association was found between the DT and HADS which indicated that both were measuring the same construct, Hospital Anxiety and Depression Scale-T (F=71.34, p<0.001), Hospital Anxiety and Depression Scale-A (F=65.81, p<0.001), Hospital Anxiety and Depression Scale-D (F=74.28, p<0.001). This study also showed that a cut-off of >=5 on DT yielded an area under Receiver analysis characteristic curve (AUC) of 0.95 with a sensitivity of 90.9% and specificity of 89.8% for HADS-T score defined as cases. On the problem checklist, respondents scoring above the cut-off of 5 on DT had a greater number of problems with family (70.0%), emotional (65.0%), physical (60.0%), practical (50.0%) and spiritual/religious (15.0%) issues. DISCUSSION: Overall, DT was a useful and simple screening tool to indicate psychological distress. The translated DT has a good sensitivity and specificity for screening psychological distress among the Malaysian breast cancer survivors. PMID- 26878946 TI - An examination of relationship between neurological soft signs and neurocognition. AB - OBJECTIVE: Neurological soft signs (NSS) and cognitive function had been examined in schizophrenia, but their relationship has remained elusive for several years. We examined the relationship between NSS and cognitive functions in the present study. METHOD: A cross sectional study was carried out. Subjects were drawn from first degree relatives of schizophrenia patients, admitted as inpatient or attending as an outpatient. Controls were recruited by word of mouth from hospital staff and visitors of hospitalized patients. Those subjects who satisfied the screening process were subjected to Cambridge Neurological Inventory for soft sign assessment and digit span test, paired associate learning test (PALT) and visuo-spatial working memory matrix (VSWMM) for cognitive function assessment. Correlation analysis and structural equation modeling (SEM) was used for analysis. RESULT: Significant negative correlation of primitive reflexes with PALT; of motor coordination with VSWMM, working memory (WM) and cognitive index; of total NSS with WM and cognitive index among first degree relatives. SEM showed that motor soft signs have important negative influence over WM. CONCLUSION: The current findings indicate that NSS have significant negative effect on cognitive functioning. PMID- 26878947 TI - Risky sexual behaviors, mental health, and history of childhood abuse among adolescents. AB - Although it seems evident that attention should be paid to risky sexual behaviors and their association with mental health among young people, this topic has not been thoroughly investigated. The present study aims to explore the relationship between sexual risk behaviors and mental health among adolescents. The participants were 251 adolescents in a juvenile detention facility (221 males and 31 females) as the "delinquent" group and 367 high school students (167 males and 200 females) as the "non-delinquent" group. A questionnaire including the Kessler 10, the Impact of Event Scale-Revised, and the Adolescent Dissociative Experience Scale was employed to measure mental health status as well as sexual risk behaviors, suicidal ideation/attempts, and abuse history. Having a history of sexual abuse or of physical abuse was associated with age when one first had sex among males with delinquent behaviors, while same tendency was observed among males without delinquent behaviors. Among the female with delinquent behaviors group, past abuse history was significantly associated with higher number of sex partners. In the non-delinquent group, better mental health among males and, contrarily, worse mental health among females were associated with having more sex partners. The results highlight the importance of addressing abuse history among females and males. Given that poor mental health status in the adolescents was associated with risky sexual behaviors, adolescents are a vulnerable group that requires attention in terms of sexual and reproductive health that integrates mental health and psychosocial components. PMID- 26878948 TI - Commentary-Asian Pearls. PMID- 26878949 TI - The study of acoustic startle reflex in male patients with chronic schizophrenia. AB - OBJECTIVE: To explore the deficits of acoustic startle reflex (ASR) that might exist in Chinese patients with schizophrenia and the effects of antipsychotics on ASR. METHODS: Participants included 25 male patients with chronic schizophrenia treated with typical antipsychotics (typical group), 25 who were treated with atypical antipsychotic clozapine (clozapine group) and 25 healthy male subjects (control group) matched for age and years of education. Startle reflex to acoustic stimuli were examined in all subjects from the three groups. At the same day of startle testing, psychopathological symptoms of the patients were assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: (1) Startle response (SR) was significantly reduced in typical group as compared to control group [(553.6+/-516.9)mV vs. (942.0+/-447.3)mV, P=0.009]. SR of clozapine group [(755.9+/-439.4)mV] was greater than that of typical group and less than that of control group, but there was no significant difference between the clozapine group and the other two. (2) Habituation (HAB) of startle reflex in typical group was significantly lower than in control group [(17.8+/-35.8)% vs. (44.9+/-28.9)%, P=0.027]. HAB of clozapine group [(22.9+/-34.1)%] was higher than that of typical group and less than that of control group, but there was no significant difference between clozapine group and the other groups. (3) Compared with healthy controls, patients of typical group exhibited the significant reduction in prepulse inhibition (PPI) of startle reflex (P=0.024) when prepulse interval (LI) was 120ms. PPI of clozapine group was higher than typical group and less than control group, but no significant differences in PPI were found between clozapine group and the other groups. While LI was 30- or 120-ms, PPI among the three groups showed not significantly different (P>0.05). (4) No significant relationship was found between PPI of different LIs and symptom scores assessed with PANSS in patients with schizophrenia (P>0.05). CONCLUSION: Our findings suggest impaired PPI in Chinese patients with schizophrenia; Atypical antipsychotic clozapine might partly improve disinhibition of startle reflex in schizophrenic patients. PMID- 26878950 TI - Intervention for first episode psychosis in India - The SCARF experience. AB - INTRODUCTION: There have been very few studies or programs in India on early intervention for first episode psychoses. This paper reports the findings of a pilot program, part of a collaboration with the Prevention and Early Intervention Program for Psychoses, Montreal. METHODOLOGY: A sample of 47 patients with first episode psychosis were followed up for 2 years. Complete data was available on 39 subjects at 2 years. This data was analyzed for socio-demographic and clinical variables and its relationship with outcomes and DUP. Those who had a PANSS score <60 and GAF >80 were categorized to be in remission (N=28) and others as continually ill (N=10). RESULTS: There was significant improvement from baseline to 1st year with maximal improvement seen at 3 months after intake. However, improvement between 1 and 2 years was not significant. More women relapsed and more men dropped out. 25 out of 28 subjects with shorter DUP (<2 years) were in remission at 2 years as against 3 out of 10 with >2 years DUP. Three different patterns of course of the disorder were found. Single episode followed by total remission for 2 years (N=20; 52.6%) was the commonest. The others were relapses followed by remissions (N=8; 21.1%), and continuous illness (N=10; 26.3%). CONCLUSION: Early intervention is effective and more so if DUP is shorter. PANSS scores and GAF at baseline are not predictive of later outcomes. Medication adherence in therapeutic engagement and psychosocial needs should be considered in the implementation of early intervention programs in our cultural context. PMID- 26878951 TI - The Singapore Early Psychosis Intervention Programme (EPIP): A programme evaluation. AB - The alarmingly long duration of untreated psychosis (DUP) in Singapore and probable severe consequences were the impetus for establishing the Early Psychosis Intervention Programme (EPIP) in 2001. In 2007, EPIP became a part of the National Mental Health Blueprint. Here, we report some of the programme's outcomes. METHOD: Consecutive patients accepted into EPIP from April 2007 to March 2011 were included. Programme inclusion criteria were: (1) age between 15 and 41 years, (2) first-episode psychotic disorder with no prior or minimal treatment, (3) no current history of substance abuse, and (4) no history of major medical or neurological illness. EPIP has incorporated an evaluation component to the clinical programme by administering regular structured assessments and generating operational statistics from our hospital's data systems. RESULTS: Between April 2007 to March 2011, 815 patients had been accepted and 795 had baseline data. 50.8% (404/795) were males, with mean age of 27 years (+/-6.5 years). Mean DUP (SD) was 14.6 (+/-25.2) months and median was 6 months. At the end of two years, 71.1% (202/284) achieved symptomatic remission as defined by the Schizophrenia Working Group, 84.9% (241/284) scored 61 or more on Global Assessment of Functioning (GAF) disability and 76.5% (274/358) had returned back to school or were gainfully employed. CONCLUSION: Being a national programme, EPIP had articulated process and outcome indicators to our stakeholders, and a periodic report card on these outcomes makes us accountable to our funders, our patients and their families. PMID- 26878952 TI - Early intervention for psychotic disorders: Real-life implementation in Hong Kong. AB - Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education. PMID- 26878953 TI - Early psychosis in Asia: Insights from Japan. AB - The largest task for psychiatry in Japan today is the deinstitutionalization of patients with psychiatric disorders. In Japan, all citizens are covered by a national health plan, and about 70% of the total cost is covered by the national health insurance scheme. At present, however, there is still no category for early intervention in the national health reimbursement schedule. Recent research has shown that the mean duration of untreated psychosis (DUP) at seven university hospitals in Japan was 17.6 months. We present data using case vignettes suggesting that pharmacotherapy might be overused in prodromal cases. The concept of an At-Risk Mental State (ARMS)/prodromal state might not yet be widely recognized among Japanese psychiatrists. We outline early intervention initiatives in Japan; The Japanese Society for Prevention and Early Intervention in Psychiatry (JSEIP), and a representative early intervention facility for young people is the "Il Bosco" in Tokyo. There are several leading centers for early intervention research and practice in Japan. Most of them are driven by university departments of psychiatry with respect to both research and clinical activities. The development of services for early intervention is expected to reduce stigmatization, prevent suicide among young persons, and promote general knowledge about mental health. There are several common or similar issues among Asian countries, including service systems, community attitudes to psychiatric illness including stigma, and dependence on pharmacotherapy. PMID- 26878955 TI - Early intervention in the Asian Century. PMID- 26878956 TI - How to come up with a research idea. PMID- 26878954 TI - Early intervention in psychosis: Insights from Korea. AB - Subjects at clinical high risk (CHR) for psychosis have been the focus of clinical attention in psychiatry for the last 15 years, leading to the development of valid and reliable diagnostic instruments to detect these individuals early in the course of their illness. These efforts have resulted in research into optimal preventive measures. Our experiences at and data from the Seoul Youth Clinic support the validity of the CHR concept and its underlying neurobiological basis and provide valuable information related to the determination of appropriate clinical interventions. The limitations of the current criteria for CHR, such as the relatively low transition rates to psychosis and the "false-positive" problem, are also common critical issues in Korea. Additionally, concerns about social stigmatization and the potential side effects of pharmacotherapy render individuals at CHR reluctant to visit clinical settings. Therefore, further investigations using a combination of predictive markers based on clinical and neurobiological studies of those at CHR are needed to refine the diagnostic criteria, overcome their current limitations including ethical issues, and develop phase-specific and individualized therapeutic interventions. PMID- 26878957 TI - 3rd Annual International Scientific Conference of the Indian Global Psychiatric Initiative (IGPI). PMID- 26878958 TI - Conference proceedings - ANCIPS 2012. PMID- 26878959 TI - Combination of CBT with fluoxetine works better for obsessive-compulsive disorder. PMID- 26878960 TI - Providing drug abuse treatment in prison: A call for action. PMID- 26878961 TI - Risk factors for suicidal ideations in bipolar depression. PMID- 26878962 TI - Diagnostic and statistical manual of mental disorders (DSM): A culture bound syndrome? PMID- 26878963 TI - The Gap Between Theory and Practice of Psychiatry in Developing countries of Asia. PMID- 26878964 TI - The second training and educational fellowship program of AFECP. PMID- 26878965 TI - Adolescents' non-core food intake: a description of what, where and with whom adolescents consume non-core foods. AB - OBJECTIVE: Little is known about adolescents' non-core food intake in the UK and the eating context in which they consume non-core foods. The present study aimed to describe types of non-core foods consumed by British adolescents in total and across different eating contexts. DESIGN: A descriptive analysis, using cross sectional data from food diaries. Non-core foods were classified based on cut-off points of fat and sugar from the Australian Guide to Healthy Eating. Eating context was defined as 'where' and 'with whom' adolescents consumed each food. Percentages of non-core energy were calculated for each food group in total and across eating contexts. A combined ranking was then created to account for each food's contribution to non-core energy intake and its popularity of consumption (percentage of consumers). SETTING: The UK National Diet and Nutrition Survey 2008-2011. SUBJECTS: Adolescents across the UK aged 11-18 years (n 666). RESULTS: Non-core food comprised 39.5 % of total energy intake and was mostly 'Regular soft drinks', 'Crisps & savoury snacks', 'Chips & potato products', 'Chocolate' and 'Biscuits'. Adolescents ate 57.0 % and 51.3 % of non-core food at 'Eateries' or with 'Friends', compared with 33.2 % and 32.1 % at 'Home' or with 'Parents'. Persistent foods consumed across eating contexts were 'Regular soft drinks' and 'Chips & potato products'. CONCLUSIONS: Regular soft drinks contribute the most energy and are the most popular non-core food consumed by adolescents regardless of context, and represent a good target for interventions to reduce non-core food consumption. PMID- 26878966 TI - Dissolved chloride markedly changes the nanostructure of the protic ionic liquids propylammonium and ethanolammonium nitrate. AB - The bulk nanostructure of 15 mol% propylammonium chloride (PACl) dissolved in propylammonium nitrate (PAN) and 15 mol% ethanolammonium chloride (EtACl) in ethanolammonium nitrate (EtAN) has been determined using neutron diffraction with empirical potential structure refinement fits. For both the PAN:PACl and EtAN:EtACl mixtures, data for three different scattering contrasts were simultaneously fit, and the structures determined and compared to that of the pure ionic liquids. Strong electrostatic interactions between chloride and cation charged groups, as well as the alcohol moiety of EtAN, lead to marked changes in local ion packing that alter the liquid structure. In PAN, the addition of chloride modifies but does not significantly disrupt the bicontinuous amphiphilic nanostructure of the IL. Tight packing of ammonium groups around chloride favours a gauche conformer for the cation which shrinks the apolar domains and brings the terminal methyls nearer the polar domains. The weakly-clustered nanostructure of EtAN, a consequence of the terminal hydroxyl, is overwhelmed by strong chloride cation interactions. Ethanolammonium binds tightly to chloride in a monodentate fashion via either its alcohol or ammonium charge centre, or through both in a bidentate arrangement by adopting a gauche or eclipsed conformer. PMID- 26878967 TI - Carbon coating may expedite the fracture of carbon-coated silicon core-shell nanoparticles during lithiation. AB - Previous studies on silicon (Si) indicate that lithiation-induced fracture of crystalline Si nanoparticles can be greatly inhibited if their diameter is reduced to below a critical scale of around 150 nm. In this paper, in situ lithiation of individual carbon-coated Si nanoparticles (Si@C NPs) is conducted which shows that Si@C NPs will fracture during lithiation even though their diameter is much smaller than 150 nm, implying a deleterious effect of the carbon coating on the integrity of the Si@C NPs during lithiation. To shed light on this effect, finite element analysis is carried out which reveals that the carbon coating, if fractured during lithiation, will induce cracks terminating at the C/Si interface. Such cracks, upon further lithiation, can immediately propagate into the Si core due to the elevated driving force caused by material inhomogeneity between the coating and core. To prevent the fracture of the carbon coating so as to protect the Si core, a design guideline is proposed by controlling the ratio between the diameter of Si core and the thickness of carbon coating. The results in this paper should be of practical value to the design and application of Si-based core-shell structured anode materials for lithium ion batteries. PMID- 26878968 TI - HSV-2 encephalitis complicated by cerebral hemorrhage in an immunocompetent person. PMID- 26878970 TI - In the centre of an epidemic: Fifteen years of LA-MRSA CC398 at the University Hospital Munster. AB - Ten years after initial publications on livestock-associated methicillin resistant Staphylococcus aureus (LA-MRSA) in 2005, we report on the course of the LA-MRSA CC398 epidemic among patients of the University Hospital Munster. This tertiary care facility is located in the Dutch-German border region (EUREGIO), which is characterized by a high density of livestock production and is hence a hotspot for the occurrence of LA-MRSA CC398. Taking advantage of the unique opportunity to track the emergence and spread of MRSA CC398 among humans from the very beginning of the epidemic until today, a total of 6555 non-duplicate MRSA isolates from all screenings and clinical specimens cultivated within the period from 2000 to 2014 were included in the analysis. Retrospectively, the first MRSA CC398 isolate (spa type t034) was obtained from a screening specimen of a patient in 2000, which represents one of the first human-associated LA-MRSA CC398 isolates reported in Europe. After sporadic detections between 2000 and 2004, this clonal lineage accounted for 9.6% of all local MRSA in 2005; a proportion which increased to 35% in 2013 and became stable since then. Considering the period from 2000 to 2014, the group of MRSA CC398 isolates comprised a total of 45 different spa types among which t011 (48.3%), t034 (39.3%) and t108 (3.5%) were predominant and so far unreported types were found. Overall, LA-MRSA CC398 emerged rapidly during the past decade, developed enormous sublineage diversity and contributed substantially to the total burden of MRSA colonization and infection at the hospital. PMID- 26878969 TI - Neural underpinnings of the evidence accumulator. AB - Gradual accumulation of evidence favoring one or another choice is considered a core component of many different types of decisions, and has been the subject of many neurophysiological studies in non-human primates. But its neural circuit mechanisms remain mysterious. Investigating it in rodents has recently become possible, facilitating perturbation experiments to delineate the relevant causal circuit, as well as the application of other tools more readily available in rodents. In addition, advances in stimulus design and analysis have aided studying the relevant neural encoding. In complement to ongoing non-human primate studies, these newly available model systems and tools place the field at an exciting time that suggests that the dynamical circuit mechanisms underlying accumulation of evidence could soon be revealed. PMID- 26878971 TI - Murine immunization with CS21 pili or LngA major subunit of enterotoxigenic Escherichia coli (ETEC) elicits systemic and mucosal immune responses and inhibits ETEC gut colonization. AB - CS21 pili of enterotoxigenic Escherichia coli (ETEC) is one of the most prevalent ETEC colonization factors. CS21 major subunit, LngA, mediates ETEC adherence to intestinal cells, and contributes to ETEC pathogenesis in a neonatal mouse infection model. The objectives of this work were to evaluate LngA major subunit purified protein and CS21 purified pili on immunogenicity and protection against ETEC colonization of mice intestine. Recombinant LngA purified protein or purified CS21 pili from E9034A ETEC strain were evaluated for immunogenicity after immunization of C57BL/6 mice. Specific anti-LngA antibodies were detected from mice serum, feces, and intestine fluid samples by ELISA assays. Protection against gut colonization was evaluated on immunized mice orally challenged with wild type E9034A ETEC strain and by subsequent quantification of bacterial colony forming units (CFU) recovered from feces. Recombinant LngA protein and CS21 pili induced specific humoral and mucosal anti-LngA antibodies in the mouse model. CS21 combined with CT delivered intranasally as well as LngA combined with incomplete Freund adjuvant delivered intraperitoneally inhibited ETEC gut colonization in a mouse model. In conclusion, both LngA purified protein and CS21 pili from ETEC are highly immunogenic and may inhibit ETEC intestinal shedding. Our data on immunogenicity and immunoprotection indicates that CS21 is a suitable vaccine candidate for a future multivalent vaccine against ETEC diarrhea. PMID- 26878972 TI - Antibodies derived from a toxoid MEFA (multiepitope fusion antigen) show neutralizing activities against heat-labile toxin (LT), heat-stable toxins (STa, STb), and Shiga toxin 2e (Stx2e) of porcine enterotoxigenic Escherichia coli (ETEC). AB - Enterotoxigenic Escherichia coli (ETEC) strains are the main cause of diarrhea in pigs. Pig diarrhea especially post-weaning diarrhea remains one of the most important swine diseases. ETEC bacterial fimbriae including K88, F18, 987P, K99 and F41 promote bacterial attachment to intestinal epithelial cells and facilitate ETEC colonization in pig small intestine. ETEC enterotoxins including heat-labile toxin (LT) and heat-stable toxins type Ia (porcine-type STa) and type II (STb) stimulate fluid hyper-secretion, leading to watery diarrhea. Blocking bacteria colonization and/or neutralizing enterotoxicity of ETEC toxins are considered effective prevention against ETEC diarrhea. In this study, we applied the MEFA (multiepitope fusion antigen) strategy to create toxoid MEFAs that carried antigenic elements of ETEC toxins, and examined for broad antitoxin immunogenicity in a murine model. By embedding STa toxoid STaP12F (NTFYCCELCCNFACAGCY), a STb epitope (KKDLCEHY), and an epitope of Stx2e A subunit (QSYVSSLN) into the A1 peptide of a monomeric LT toxoid (LTR192G), two toxoid MEFAs, 'LTR192G-STb-Stx2e-STaP12F' and 'LTR192G-STb-Stx2e-3xSTaP12F' which carried three copies of STaP12F, were constructed. Mice intraperitoneally immunized with each toxoid MEFA developed IgG antibodies to all four toxins. Induced antibodies showed in vitro neutralizing activities against LT, STa, STb and Stx2e toxins. Moreover, suckling piglets born by a gilt immunized with 'LTR192G-STb-Stx2e-3xSTaP12F' were protected when challenged with ETEC strains, whereas piglets born by a control gilt developed diarrhea. Results from this study showed that the toxoid MEFA induced broadly antitoxin antibodies, and suggested potential application of the toxoid MEFA for developing a broad spectrum vaccine against ETEC diarrhea in pigs. PMID- 26878974 TI - Controlling levonorgestrel binding and release in a multi-purpose prevention technology vaginal ring device. AB - Despite a long history of incorporating steroids into silicone elastomers for drug delivery applications, little is presently known about the propensity for irreversible drug binding in these systems. In this study, the ability of the contraceptive progestin levonorgestrel to bind chemically with hydrosilane groups in addition-cure silicone elastomers has been thoroughly investigated. Cure time, cure temperature, levonorgestrel particle size, initial levonorgestrel loading and silicone elastomer type were demonstrated to be key parameters impacting the extent of levonorgestrel binding, each through their influence on the solubility of levonorgestrel in the silicone elastomer. Understanding and overcoming this levonorgestrel binding phenomenon is critical for the ongoing development of a number of drug delivery products, including a multi-purpose technology vaginal ring device offering simultaneous release of levonorgestrel and dapivirine - a lead candidate antiretroviral microbicide - for combination HIV prevention and hormonal contraception. PMID- 26878977 TI - Preface to the IUFRO RG7.01 special section "Global Challenges of Air Pollution and Climate Change to Forests". PMID- 26878975 TI - Involvement of transfusion unit staff in the informed consent process. AB - BACKGROUND AND OBJECTIVES: Obtaining informed consent (IC) for a blood transfusion is an absolute requirement. In this study, we compared the depth of understanding of blood transfusion among patients with or without an explanation by the transfusion unit staff and evaluated the usefulness of this intervention in obtaining IC. MATERIALS AND METHODS: Expert staff from the transfusion unit started to provide patients with a basic explanation of blood transfusion (intervention group, n = 129). The efficacy of this strategy was assessed by comparison with explanation given by the primary doctors only (conventional group, n = 31). We performed a questionnaire survey to analyze the length of time spent providing information of blood transfusion and the depth of understanding of blood transfusion in the two groups. RESULTS: The median time in providing information in the conventional and intervention groups was 6 and 20 minutes, respectively (P < 0.0001). Patients in the intervention group had a better understanding of several key points on blood transfusion than those in the conventional group. CONCLUSION: Our results show that expert staff from the transfusion unit should be involved in obtaining IC for a blood transfusion. Patients who were provided information by transfusion unit staff were more likely to have a better understanding of the risks and benefits of transfusion. PMID- 26878973 TI - Sonoporation enhances liposome accumulation and penetration in tumors with low EPR. AB - The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFalpha-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR. PMID- 26878978 TI - Patients with cancer at the margins of reproductive age had reduced levels of anti-Mullerian hormone compared with patients experiencing infertility. AB - OBJECTIVE: To compare the ovarian reserves between female patients with cancer and patients experiencing infertility. METHODS: A retrospective age-matched observational study was performed at Rotunda Hospital, Dublin. The study group included data from all female oncology patients attending for oocyte or embryo cryopreservation between January 1, 2009 and December 31, 2013. Anti-Mullerian hormone (AMH) levels were recorded at patients' initial visits before beginning chemotherapy or radiotherapy. The control group included patients without cancer who had their AMH levels recorded to investigate fertility or as a baseline level prior to beginning assisted reproductive treatment. RESULTS: The records of 118 oncology and 5231 control patients from the study period were identified. There was no difference in AMH levels between patients in the oncology and control groups aged 30-38years; however, significantly lower AMH levels were observed in patients in the oncology group aged 29years and younger (17.89pmol/L vs 23.35pmol/L; P=0.015), or at least 39years (2.65pmol/L vs 5.87pmol/L; P=0.028). CONCLUSION: Before commencing chemotherapy or radiotherapy, patients in the oncology group at the margins of reproductive age had a diminished ovarian reserve compared with the control group. This should be considered when planning optimal doses of follicular stimulating hormone as part of controlled ovarian stimulation regimes performed for embryo or oocyte cryopreservation prior to chemotherapy or radiotherapy. PMID- 26878979 TI - Too bad: Bias for angry faces in social anxiety interferes with identity processing. AB - The recognition of faces across incidences is a complex function of the human brain and a crucial ability for communication and daily interactions. This first study on ERP correlates of emotional face learning in social anxiety disorder (SAD) investigates whether the known attentional bias for threatening faces leads to a corresponding memory bias. Therefore, 21 patients with SAD and 21 healthy controls (HCs) learned faces with emotional facial expressions (neutral, happy, and angry) and were later asked to recognize these out of novel identities all presented with a neutral facial expression. EEG was recorded throughout. Behaviorally, the faces' emotional expression modulated later recognition in terms of accuracy, response times, signal detection parameters and ratings of valence, but with better performance for happy than angry faces in HC as well as in SAD. In the learning phase, attention- and memory-associated event-related potentials (ERPs) P100, N170, P200, N250/EPN, and LPP indicated enhanced processing of angry faces, which was restricted to patients with SAD in N250/EPN and LPP. In the test phase, familiarity effects emerged in N250, FN400 and LPP. While N250 was affected by learned-angry faces, FN400 and LPP reflected image learning of neutral faces, which was restricted to SAD in LPP. We replicated the attentional bias to threatening faces, which was not restricted to early ERP components, but was prolonged to later stages of conscious processing, especially in SAD. In contrast to what had been expected, sustained hypervigilance to the emotional content seems to have impaired the processing of the facial identity, resulting in a happy face advantage at the behavioral level. This could be explained by prominent models assuming separate processing of facial emotion and identity. Hypervigilance in SAD might be a disadvantage in those studies focusing on other aspects of face processing than emotion. PMID- 26878982 TI - Selective membrane disruption by the cyclotide kalata B7: complex ions and essential functional groups in the phosphatidylethanolamine binding pocket. AB - The cyclic cystine knot plant peptides called cyclotides are active against a wide variety of organisms. This is primarily achieved through membrane binding and disruption, in part deriving from a high affinity for phosphatidylethanolamine (PE) lipids. Some cyclotides, such as kalata B7 (kB7), form complexes with divalent cations in a pocket associated with the tyrosine residue at position 15 (Tyr15). In the current work we explore the effect of cations on membrane leakage caused by cyclotides kB1, kB2 and kB7, and we identify a functional group that is essential for PE selectivity. The presence of PE-lipids in liposomes increased the membrane permeabilizing potency of the cyclotides, with the potency of kB7 increasing by as much as 740-fold. The divalent cations Mn(2+), Mg(2+) and Ca(2+) had no apparent effect on PE selectivity. However, amino acid substitutions in kB7 proved that Tyr15 is crucial for PE-selective membrane permeabilization on various liposome systems. Although the tertiary structure of kB7 was maintained, as reflected by the NMR solution structure, mutating Tyr into Ser at position 15 resulted in substantially reduced PE selectivity. Ala substitution at the same position produced a similar reduction in PE selectivity, while substitution with Phe maintained high selectivity. We conclude that the phenyl ring in Tyr15 is critical for the high PE selectivity of kB7. Our results suggest that PE-binding and divalent cation coordination occur in the same pocket without adverse effects of competitive binding for the phospholipid. PMID- 26878981 TI - Effects of cerebellar transcranial direct current stimulation on attentional processing of the stimulus: Evidence from an event-related potentials study. AB - Attentional processing consists of a set of processes that manage the flow of information through the nervous system and appropriately allocate attentional resources to relevant stimuli. Specific networks in the frontal and parietal regions appear to be involved in attention. The cerebellum has been identified as a subcortical structure that interacts with cortical brain areas, thereby controlling attentional processes. The aim of this study was to investigate the role of the cerebellum in attentional processing of the stimulus using a P300 Novelty task. We studied the effects of transcranial Direct Current Stimulation (tDCS) delivered over the left cerebellar hemisphere in cathodal, anodal and sham sessions on the P300 components in healthy subjects. Only cathodal cerebellar tDCS significantly reduced the amplitude of the N1, N2 and P3 components for both the target and novel stimuli. Moreover, N1 latency for all the stimuli was shorter after the cathodal tDCS session than after the sham or anodal sessions. These results point to a role of the cerebellum in attentional processing of the stimulus. The cerebellum may act indirectly by regulating and managing the activation and inhibition levels of the cortical areas involved in attentional networks. PMID- 26878983 TI - Normalization of doxorubicin release from graphene oxide: New approach for optimization of effective parameters on drug loading. AB - Graphene oxide (GO) has been recently introduced as a suitable anticancer drug carrier, which could be loaded with doxorubicin (DOX) as a general chemotherapy agent. Herein, the attempts were made to optimize the effective parameters on both loading and release of DOX on GO. GO and GO-DOX were characterized using transition electron microscopy , zeta potential, Raman spectroscopy, UV-visible spectroscopy, and Fourier transform infrared spectroscopy. In addition, loading and releasing behaviors of DOX on GO were studied in terms of different temperature and pH values. The primary optimized values of pH and temperature for best-loaded amount of DOX were 8.9 and 309 K, respectively. Moreover, we found that the smallest amount of released DOX, in pH of cancer microenvironment (5.4), occurs when DOX had been previously loaded in pH 7.8 and 310 K. Although the highest amount of loaded DOX was in basic pH, the results of efficient release of DOX from the GO-DOX complex and also cellular toxicity assay revealed that the best pH for loading of DOX on GO was 7.8. Therefore, in addition to optimization of parameters for efficient loading of DOX on GO, this study suggested that normalization of a released drug compared with the amount of a loaded drug could be a new approach for optimization of drug loading on nanocarriers. PMID- 26878980 TI - Hemispheric asymmetry in event knowledge activation during incremental language comprehension: A visual half-field ERP study. AB - During incremental language comprehension, the brain activates knowledge of described events, including knowledge elements that constitute semantic anomalies in their linguistic context. The present study investigates hemispheric asymmetries in this process, with the aim of advancing our understanding of the neural basis and functional properties of event knowledge activation during incremental comprehension. In a visual half-field event-related brain potential (ERP) experiment, participants read brief discourses in which the third sentence contained a word that was either highly expected, semantically anomalous but related to the described event (Event-Related), or semantically anomalous but unrelated to the described event (Event-Unrelated). For both visual fields of target word presentation, semantically anomalous words elicited N400 ERP components of greater amplitude than did expected words. Crucially, Event-Related anomalous words elicited a reduced N400 relative to Event-Unrelated anomalous words only with left visual field/right hemisphere presentation. This result suggests that right hemisphere processes are critical to the activation of event knowledge elements that violate the linguistic context, and in doing so informs existing theories of hemispheric asymmetries in semantic processing during language comprehension. Additionally, this finding coincides with past research suggesting a crucial role for the right hemisphere in elaborative inference generation, raises interesting questions regarding hemispheric coordination in generating event-specific linguistic expectancies, and more generally highlights the possibility of functional dissociation of event knowledge activation for the generation of elaborative inferences and for linguistic expectancies. PMID- 26878985 TI - Mutational analysis of H3F3B gene in acute leukaemias and solid tumours. PMID- 26878984 TI - Multiple sevoflurane exposures in infant monkeys do not impact the mother-infant bond. AB - Exposure to general anesthesia during the postnatal period is associated with death of brain cells as well as long-term impairments in cognitive and emotional behavior in animal models. These models are critical for investigating mechanisms of pediatric anesthetic neurotoxicity as well as for testing potential strategies for preventing or mitigating this toxicity. Control conditions for anesthesia exposure involve separation of conscious infants from their mothers for variable periods of time, which could have its own effect on subsequent behavior because of stress to the mother and/or infant as a consequence of separation.We are conducting a long-term study of infant rhesus monkeys exposed three times for 4h each to sevoflurane anesthesia during the first six postnatal weeks, with a comparison condition of control infant monkeys that undergo brief maternal separations on the same schedule, to equate the period of time each infant is conscious and separated from its mother. Because mothers are separated from their infants longer for infants in the anesthesia condition, this could modify maternal behavior toward the infant, which may influence subsequent socioemotional behavior in the infants. In this study, we analyzed maternal behavior immediately after the first post-anesthesia (or control) reunion, as well as during reintroduction of the mother-infant pair to the larger social group 24 hpost-anesthesia or control separation, and found no differences between the conditions with mothers spending most of their time in contact with infants in all conditions analyzed. This indicates that the different durations of maternal separation in this study design do not impact the mother-infant bond, strengthening conclusions that subsequent differences in behavior between monkeys exposed to anesthesia compared to controls are a consequence of anesthesia exposure and not differential maternal behavior in the two conditions. PMID- 26878987 TI - Copper-Catalyzed Intramolecular Oxidative Amination of Unactivated Internal Alkenes. AB - A copper-catalyzed oxidative amination of unactivated internal alkenes has been developed. The Wacker-type oxidative alkene amination reaction is traditionally catalyzed by a palladium through a mechanism involving aminopalladation and beta hydride elimination. Replacing the precious and scarce palladium with a cheap and abundant copper for this transformation has been challenging because of the difficulty associated with the aminocupration of internal alkenes. The combination of a simple copper salt, without additional ligand, as the catalyst and Dess-Martin periodinane as the oxidant, promotes efficiently the oxidative amination of allylic carbamates and ureas bearing di- and trisubstituted alkenes leading to oxazolidinones and imidazolidinones. Preliminary mechanistic studies suggested a hybrid radical-organometallic mechanism involving an amidyl radical cyclization to form the key C-N bond. PMID- 26878986 TI - MicroRNA-132 and microRNA-223 control positive feedback circuit by regulating FOXO3a in inflammatory bowel disease. AB - BACKGROUND AND AIM: Although many progresses have been achieved for inflammatory bowel disease (IBD), it is still remained as idiopathic disease to be completely controlled. MicroRNAs (miRNAs) have been identified as key players in many human diseases through degradation or translational inhibition of target genes. Because role of miRNAs in IBD is not completely understood yet, we need to identify miRNAs as novel targets for treatment of IBD. METHODS: Microarray analysis for miRNAs was performed using dextran sulfate sodium-induced colitis samples and selected differentially regulated miRNAs. Candidate genes were validated using in vitro system and IBD patient samples. Molecular mechanism for regulation of inflammatory signaling was identified using gene modulation system of miRNAs. RESULTS: We selected 14 upregulated and 15 downregulated miRNAs through microarray analysis. Among candidate miRNAs, significant upregulation of miR-132 and miR-223 was confirmed in inflamed mouse tissues as well as human IBD patient tissues. Through bioinformatics analysis, we identified FOXO3a as direct target of miRNAs and confirmed regulatory mechanism using luciferase assay. Expression of miRNAs clearly suppressed the level of IkappaBalpha through downregulation of FOXO3a, leading to enhanced NF-kappaB signaling to promote the production of pro inflammatory cytokines. The downregulation of FOXO3a concurrent with upregulation of cytokines was significantly reversed by sequestration of miRNAs with miRNA sponges. CONCLUSIONS: Our findings provided the evidences that miR-132 and 223 are critical mediators in positive circuit for pathogenesis of IBD by negatively regulating FOXO3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for IBD treatment. PMID- 26878988 TI - A prospective study assessing the etiology of Diabetes mellitus among Jordanian patients. AB - BACKGROUND: Diabetes mellitus has considerable public health implications for communities, individuals, and health services. Increasing prevalence of diabetes all over the world intensifies the demand for health care services, and particularly for inpatient care. AIM: The present study aims to assess the current prevalence of diabetes and its etiology among hospitalized Jordanian adults. METHODS: This was a cross sectional study conducted at Specialist Hospital (SH) in the Jordanian capital of Amman, with data collection taking place between June and August 2015, and data was extracted manually from medical records. Patients were divided into three groups: (a) those with a medical history of diabetes, (b) those with unrecognized diabetes or new hyperglycemia, and (c) those with no diabetes. Data management and analysis were conducted using the SPSS program. Means +/-SD were used to present all continuous variables, as well as the numbers and percentages for categorical variables, and we used analysis of variance (ANOVA) to compare between means. For differences between categorical variables, we used (x(2)). A P-value of less than 0.05 was considered significant. RESULTS: A total of 392 patients (266 female, 126 male) were admitted during the 10-week study period. Of these, 204 fell into category (a), 45 into category (b), and 143 into category (c). Diabetes was the principal diagnosis in 52% of the hospitalizations. Patients who had diabetes or new hyperglycemia were considerably older than non-diabetic patients. The five most common reasons for hospitalization were congestive heart failure (25.0%), pneumonia (22.5%), DKA (22.0%), coronary atherosclerosis (16.20%), and septicemia (14.20%). CONCLUSION: The common etiologies for hospitalization were congestive heart failure, pneumonia, DKA, coronary atherosclerosis, and septicemia. Keeping in view the results of this study it is recommend that regular screening should be performed for diabetic patients, as this will increase the chances that many diabetes complications will be prevented, particularly for elderly subjects. PMID- 26878989 TI - Integrin alphaE (CD103) is induced but plays no pathogenic role in psoriasiform skin lesions of TGFbeta1 transgenic mice. AB - T-cells expressing alphaE (CD103), an integrin induced by TGFbeta on T-cells in vitro, accumulate within epithelia in inflammatory disorders, including psoriasis. However, it is unclear, if and how alphaE (CD103) contributes to skin inflammation. Using two complementary approaches, we have investigated alphaE (CD103) in psoriasis-like skin inflammation of mice with transgenic epidermal expression of human TGFbeta1: alphaE (CD103) was inhibited by function-blocking antibodies in vivo, and double-mutants with additional alphaE (CD103)-depletion were generated in two different genetic backgrounds. Epidermal hTGFbeta1 expression was associated with prominent expression of alphaE (CD103) on infiltrating cells. However, neither treatment with alphaE (CD103)-blocking antibodies nor deficiency of alphaE (CD103) in double-mutant mice altered the psoriasis-like phenotype. In addition, histopathological and flow cytometric analyses revealed similar pathological skin alterations and lymphocyte subgroups in the different mouse strains. Thus, while alphaE (CD103) expression is indeed associated with hTGFbeta1 in vivo, it has little, if any, influence on the course of the psoriasis-like phenotype in K5.hTGFbeta1 transgenic mice. PMID- 26878990 TI - Characterization of immunoglobulin E plasma cells that are elevated in the upper airway mucosa of nonatopic patients with chronic rhinosinusitis without nasal polyps. AB - BACKGROUND: The immunologic mechanisms driving inflammation in the upper airways of patients with chronic rhinosinusitis (CRS) are poorly understood. Previous studies have shown that B cells and immunoglobulin E (IgE) levels are elevated in the nasal tissue of patients with atopic chronic rhinosinusitis without nasal polyps (CRSsNP). However, less is known regarding B cell subsets and IgE producing plasmablasts in nonatopic CRSsNP patients. METHODS: Human blood and ethmoid sinus mucosa samples were analyzed from control (n = 6) and nonatopic CRSsNP (n = 11) patients. Tissue samples were evaluated using high-dimensional flow cytometry. RESULTS: A population of IgE antibody secreting cells is significantly increased in situ within inflamed nasal tissue of nonatopic CRSsNP subjects when compared to control nasal tissue and the circulating peripheral blood (p < 0.05). This IgE plasma cell population displays ~90% cell surface Ig lambda light chain, is mitotically active (Ki-67(+)), and displays intracellular IgE expression. The predominant B cell population expressing IgE are plasmablasts (CD38(high), CD138(-)) not typically found in the blood or peripheral tissue of these patients. CONCLUSION: The nasal mucosa from nonatopic CRSsNP patients demonstrate a significant regional spike in resident in situ IgE plasmablast cells not seen in control nasal tissue or peripheral blood from the same patient. The restricted expression of Ig lambda light chain in this mitotically active IgE plasmablast population supports the hypothesis of aberrant B cell proliferation in the context of CRS. These findings suggest the presence of a unique regional immune microenvironment for B cell priming and/or selection within chronically inflamed airway tissues. PMID- 26878991 TI - Size Fractionation of Two-Dimensional Sub-Nanometer Thin Manganese Dioxide Crystals towards Superior Urea Electrocatalytic Conversion. AB - A universal technique has been proposed to sort two-dimensional (2D) sub nanometer thin crystals (manganese dioxide MnO2 and molybdenum disulfide MoS2 ) according to their lateral dimensions. This technique is based on tuning the zeta potential of their aqueous dispersions which induces the selective sedimentation of large-sized 2D crystals and leaves the small-sized counterparts in suspension. The electrocatalytic properties of as-obtained 2D ultrathin crystals are strongly dependent on their lateral size. As a proof-of-concept study, the small-sized MnO2 nanocrystals were tested as the electrocatalysts for the urea-oxidation reaction (UOR), which showed outstanding performance in both half reaction and full electrolytic cell. A mechanism study reveals the enhanced performance is associated with the remarkable structural properties of MnO2 including ultrathin (ca. 0.95 nm), laterally small-sized (50-200 nm), and highly exposed active centers. PMID- 26878992 TI - How Interfaces Affect the Acidity of the Anilinium Ion. AB - The acidity of a compound is a fundamental property that dictates molecular speciation and reactivity in solution. Measurements of acidity of simple molecules in interfacial environments are rarely carried out but assumptions often are made that the difference is sufficiently small that the change can be ignored. The effect of oil-surfactant-water interfaces in reverse micellar systems on the pKa value of the anilinium ion was measured using titrations by NMR spectroscopy as the size of the bis(2-ethylhexyl)sulfosuccinate (AOT)/isooctane reverse micelles decreased. The pKa was observed to drop from 4.85+/-0.02 to 4.62+/-0.02 in water as the reverse micelle decreased from w(0) 10 to 4 (that is down to a reverse micellar radius of about 2 nm). NOSEY experiments demonstrated that the aniline moiety resides within the surfactant interface with the amine/ammonium moiety protruding into the waterpool bridging the interface. The presence of the aniline was found to have modest and variable effect on the size of the reverse micelles as observed using dynamic light scattering. Our experimental results provide information important to theoretical studies, which explore interface phenomena and provide a framework for information on such simple molecules. These studies quantitate the small but significant effect on the pKa values upon placement of an aromatic amine molecule at a hydrophilic hydrophobic interface. PMID- 26878993 TI - PROP taster status, food preferences and consumption of high-calorie snacks and sweet beverages among 6-year-old ethnically diverse children. AB - A healthy diet is important for optimal growth and development in children. Food preferences are a main determinant of children's intake. The aim of this study was to examine the associations of 6-n-propylthiouracil (PROP) taster status (taste sensitivity to PROP) with children's food preferences and consumption of high-calorie snacks and sweet beverages among ethnically diverse children. We analysed data from 5585 6-year-old children enrolled in the Generation R Study, a birth cohort study in Rotterdam, the Netherlands. PROP taster status was evaluated using a suprathreshold screening solution. Food preferences of the children were assessed by a two-stage protocol using photographs of eight food items (candy, chocolate, mayonnaise, whipped cream, soup, potato chips, carrot and bread), yielding both hedonic ratings (1-3) and rank order scores (1-8). Univariate and multivariable linear and logistic regression analyses were performed, using tasters as the reference group. Non-tasters had a slightly higher preference for carrots (beta: -0.07; 95% CI: -0.13, -0.02 and beta: -0.15; 95% CI: -0.27, -0.02 for hedonic ratings and rank order scores, respectively) and bread (hedonic ratings; beta: -0.06; 95% CI: -0.11, -0.01) compared with tasters. No differences were found in children's preference for sweet, fat or salty food items. Furthermore, there were no associations of PROP taster status with the consumption of high-calorie snacks >= 2 times/day (aOR: 1.06; 95% CI: 0.91,1.24) or sweet beverages >= 3 glasses/day (aOR: 1.06; 95% CI: 0.92,1.23). Other factors relating to the family food environment may be more important for young children's food preferences and consumption of high-calorie snacks and sweet beverages than their innate taste sensitivity. PMID- 26878994 TI - Course of iron parameters in HFE-hemochromatosis patients during initial treatment with erythrocytapheresis compared to phlebotomy. AB - Current treatment for newly diagnosed patients with hereditary hemochromatosis (HH) and iron overload consist of weekly phlebotomy or less frequent and more personalized erythrocytapheresis. Previous observations during phlebotomy suggest an increase in intestinal iron uptake caused by lowering of hepcidin as a result of intensive bloodletting. It is not known whether such an effect is present or even more pronounced using erythrocytapheresis since a larger amount of iron is extracted per procedure. In this study we aimed to assess the effect of erythrocytapheresis on the course of iron parameters, with special focus on serum hepcidin. We performed a retrospective proof-of-principle observational study, comparing serum iron parameters in 12 males during the depletion phase using either phlebotomy (n = 6) or erythrocytapheresis (n = 6). Decreases in serum ferritin over time were similar for both treatments but more pronounced using erythrocytapheresis when expressed per treatment procedure. Hemoglobin did not change during erythrocytapheresis, whereas during phlebotomy decreased with 10%. Increase of erythropoietin and soluble transferrin receptor and decrease in transferrin saturation were similar for both treatments. Reduction in serum hepcidin was higher (50% versus 25% of initial value) and occurred more early using phlebotomy (10 versus 20 weeks after start). In aggregate, compared to phlebotomy, the less frequent and more personalized erythrocytapheresis leads to a more pronounced decrease in serum ferritin per treatment procedure, without a larger decrease in serum hepcidin. This may be clinically relevant and may prevent an increase in intestinal iron uptake and an ensuing vicious circle of more frequent treatment procedures. J. Clin. Apheresis 31:564-570, 2016. (c) 2015 Wiley Periodicals, Inc. PMID- 26878996 TI - Synthesis of Highly Functionalized 4-Aminoquinolines. AB - A diverse set of highly substituted 4-aminoquinolines was synthesized from ynamides, triflic anhydride, 2-chloropyridine, and readily accessible amides in a mild one-step procedure. PMID- 26878997 TI - Polymer/Graphene Hybrids for Advanced Energy-Conversion and -Storage Materials. AB - Polymer/graphene-based materials with interesting physical and chemical properties have been attracting considerable attention and have been shown to have great potential as active materials in the field of energy conversion and storage. In this review, we focus on recent significant advances in the fabrication and application of polymer/graphene hybrids as electrocatalysts and electrode materials. Synthetic strategies and application of these materials in energy conversion and storage are presented, particularly in devices such as fuel cells, actuators, and supercapacitors, accompanied with a discussion of the challenges and research directions necessary for the future development of polymer/graphene hybrids. PMID- 26878998 TI - The Relationships Between Parasympathetic Function and Pain Perception: The Role of Anxiety. AB - BACKGROUND: Previous studies have identified relationships between autonomic function and pain perception. Anxiety was found to influence both autonomic and pain responses. We examined the effect of anxiety level on parasympathetic function and pain perception as well as on the relationships between these 2 systems. METHODS: Thirty healthy females were divided into high- and low-anxiety groups according to their trait anxiety levels. Parasympathetic function was obtained using heart rate variability, deep breathing, and Valsalva ratios. Pain perception parameters of heat pain thresholds, pain rating of supra-thresholds stimulus, mechanical temporal summation, and conditioned pain modulation response were examined. RESULTS: The low-anxiety and high-anxiety groups exhibited no significant differences in the parasympathetic function and pain perception parameters. Assessment of the associations revealed that in the high-anxiety group, higher mean ratings of the tonic heat pain stimulus were significantly correlated with higher rMSSD (r2 = 0.358, P = 0.019), but this was not found for the low-anxiety group (P = 0.282). In addition, in the high-anxiety group, efficient conditioned pain modulation response was correlated with higher deep breathing ratio (r2 = 0.363, P = 0.023); however, in the low-anxiety group, the correlation did not reach significance (P = 0.109). CONCLUSIONS: This study demonstrates the role of anxiety level on the relationships between parasympathetic function and pain perception. We suggest that a situation of high anxiety leads to higher norepinephrine levels that can influence both parasympathetic function and pain perception, thus explaining the significant relationships found between these 2 systems only in subjects with high anxiety. PMID- 26878999 TI - Study of SEM preparation artefacts with correlative microscopy: Cell shrinkage of adherent cells by HMDS-drying. AB - One of the often reported artefacts during cell preparation to scanning electron microscopy (SEM) is the shrinkage of cellular objects, that mostly occurs at a certain time-dependent stage of cell drying. Various methods of drying for SEM, such as critical point drying, freeze-drying, as well as hexamethyldisilazane (HMDS)-drying, were usually used. The latter becomes popular since it is a low cost and fast method. However, the correlation of drying duration and real shrinkage of objects was not investigated yet. In this paper, cell shrinkage at each stage of preparation for SEM was studied. We introduce a shrinkage coefficient using correlative light microscopy (LM) and SEM of the same human mesenchymal stem cells (hMSCs). The influence of HMDS-drying duration on the cell shrinkage is shown: the longer drying duration, the more shrinkage is observed. Furthermore, it was demonstrated that cell shrinkage is inversely proportional to cultivation time: the longer cultivation time, the more cell spreading area and the less cell shrinkage. Our results can be applicable for an exact SEM quantification of cell size and determination of cell spreading area in engineering of artificial cellular environments using biomaterials. SCANNING 38:625-633, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26879000 TI - Red Phosphorescent Bis-Cyclometalated Iridium Complexes with Fluorine-, Phenyl-, and Fluorophenyl-Substituted 2-Arylquinoline Ligands. AB - Red phosphorescent iridium(III) complexes based on fluorine-, phenyl-, and fluorophenyl-substituted 2-arylquinoline ligands were designed and synthesized. To investigate their electrophosphorescent properties, devices were fabricated with the following structure: indium tin oxide (ITO)/4,4',4''-tris[2 naphthyl(phenyl)amino]triphenylamine (2-TNATA)/4,4'-bis[N-(1-naphthyl)-N phenylamino]biphenyl (NPB)/4,4'-bis(N-carbazolyl)-1,1'-biphenyl (CBP): 8% iridium (III) complexes/bathocuproine (BCP)/tris(8-hydroxyquinolinato)aluminum (Alq3)/8 hydroxyquinoline lithium (Liq)/Al. All devices, which use these materials showed efficient red emissions. In particular, a device exhibited a saturated red emission with a maximum luminance, external quantum efficiency, and luminous efficiency of 14200 cd m(-2), 8.44%, and 6.58 cd A(-1) at 20 mA cm(-2), respectively. The CIE (x, y) coordinates of this device are (0.67, 0.33) at 12.0 V. PMID- 26879001 TI - Intranasal Insulin Prevents Anesthesia-Induced Spatial Learning and Memory Deficit in Mice. AB - Elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer's disease (AD). At present, there is no treatment that can prevent anesthesia-induced postoperative cognitive dysfunction. Here, we treated mice with daily intranasal administration of insulin (1.75 U/day) for one week before anesthesia induced by intraperitoneal injection of propofol and maintained by inhalation of sevoflurane for 1 hr. We found that the insulin treatment prevented anesthesia-induced deficit in spatial learning and memory, as measured by Morris water maze task during 1-5 days after exposure to anesthesia. The insulin treatment also attenuated anesthesia-induced hyperphosphorylation of tau and promoted the expression of synaptic proteins and insulin signaling in the brain. These findings show a therapeutic potential of intranasal administration of insulin before surgery to reduce the risk of anesthesia-induced cognitive decline and AD. PMID- 26879002 TI - Impact of Mean Platelet Volume on Long-Term Mortality in Chinese Patients with ST Elevation Myocardial Infarction. AB - We investigated the association between mean platelet volume (MPV) and risk of all-cause mortality in Chinese patients with ST-Elevation Myocardial Infarction (STEMI). We enrolled 1836 patients with STEMI in Xuanwu Hospital from January 2008 to December 2013. Based on MPV, patients were categorized into the following groups: < 9.5 fL (n = 85), 9.5-11.0 fL (n = 776), 11.1-12.5 fL (n = 811) and >12.5 fL (n = 164), respectively. Mean duration of follow-up was 56.9 months, and 197 patients (10.7%) died during follow-up. All-cause mortality rates were compared between groups. The lowest mortality occurred in patients with MPV between 9.5-11.0 fL, with a multivariable-adjusted hazard ratio (HR) of 1.15(95%CI 0.62-1.50), 1.38(95%CI 1.20-1.68), and 1.72(95%CI 1.41-1.96) in patients with MPV of <.5, 11.1-12.5 and >12.5 fL, respectively. Therefore, increased MPV was associated with all-cause mortality in Chinese patients with STEMI. MPV might be useful as a marker for risk stratification in Chinese patients with STEMI. PMID- 26879003 TI - Engineering of a modular and synthetic phosphoketolase pathway for photosynthetic production of acetone from CO2 in Synechococcus elongatus PCC 7942 under light and aerobic condition. AB - Capture and conversion of CO2 to valuable chemicals is intended to answer global challenges on environmental issues, climate change and energy security. Engineered cyanobacteria have been enabled to produce industry-relevant chemicals from CO2 . However, the final products from cyanobacteria have often been mixed with fermented metabolites during dark fermentation. In this study, our engineering of Synechococcus elongatus PCC 7942 enabled continuous conversion of CO2 to volatile acetone as sole product. This process occurred during lighted, aerobic culture via both ATP-driven malonyl-CoA synthesis pathway and heterologous phosphoketolase (PHK)-phosphotransacetylase (Pta) pathway. Because of strong correlations between the metabolic pathways of acetate and acetone, supplying the acetyl-CoA directly from CO2 in the engineered strain, led to sole production of acetone (22.48 mg/L +/- 1.00) without changing nutritional constraints, and without an anaerobic shift. Our engineered S. elongatus strains, designed for acetone production, could be modified to create biosolar cell factories for sustainable photosynthetic production of acetyl-CoA-derived biochemicals. PMID- 26879004 TI - Is yolk sac tumor related to the pathophysiology of low birthweight? AB - An 8-year-old Japanese girl was admitted with an ovarian yolk sac tumor. Regarding birth history, the patient had been delivered by cesarean section at 25 weeks of gestation with a birthweight of 711g. She had required neonatal intensive care including oxygenation, various medications, and tests. After surgery and chemotherapy, there was no recurrence for 2 years, at the time of writing. Yolk sac tumor, which is a malignant germ cell tumor, is rare in children. Although the cause and risk factors are unclear, it has been reported that malignant germ cell tumors in childhood have been associated with pathophysiology at birth. Given that premature infants are more likely to survive due to advances in perinatal care, it is expected that such cases will increase in the near future. We suggest that children born prematurely require careful follow up. PMID- 26879005 TI - Proteome quantification of cotton xylem sap suggests the mechanisms of potassium deficiency-induced changes in plant resistance to environmental stresses. AB - Proteomics was employed to investigate the molecular mechanisms of apoplastic response to potassium(K)-deficiency in cotton. Low K (LK) treatment significantly decreased the K and protein contents of xylem sap. Totally, 258 peptides were qualitatively identified in the xylem sap of cotton seedlings, of which, 90.31% were secreted proteins. Compared to the normal K (NK), LK significantly decreased the expression of most environmental-stress-related proteins and resulted in a lack of protein isoforms in the characterized proteins. For example, the contents of 21 Class SH peroxidase isoforms under the LK were 6 to 44% of those under the NK and 11 its isoforms were lacking under the LK treatment; the contents of 3 chitinase isoforms under LK were 11-27% of those under the NK and 2 its isoforms were absent under LK. In addition, stress signaling and recognizing proteins were significantly down-regulated or disappeared under the LK. In contrast, the LK resulted in at least 2-fold increases of only one peroxidase, one protease inhibitor, one non-specific lipid-transfer protein and histone H4 and in the appearance of H2A. Therefore, K deficiency decreased plant tolerance to environmental stresses, probably due to the significant and pronounced decrease or disappearance of a myriad of stress-related proteins. PMID- 26879006 TI - Post-illumination activity of SnO2 nanoparticle-decorated Cu2O nanocubes by H2O2 production in dark from photocatalytic "memory". AB - Most photocatalysts only function under illumination, while many potential applications require continuous activities in dark. Thus, novel photocatalysts should be developed, which could store part of their photoactivity in "memory" under illumination and then be active from this "memory" after the illumination is turned off for an extended period of time. Here a novel composite photocatalyst of SnO2 nanoparticle-decorated Cu2O nanocubes is developed. Their large conduction band potential difference and the inner electrostatic field formed in the p-n heterojunction provide a strong driving force for photogenerated electrons to move from Cu2O to SnO2 under visible light illumination, which could then be released to react with O2 in dark to produce H2O2 for its post-illumination activity. This work demonstrates that the selection of decoration components for photocatalysts with the post-illumination photocatalytic "memory" could be largely expanded to semiconductors with conduction band potentials less positive than the two-electron reduction potential of O2. PMID- 26879007 TI - The effect of hydroxyethyl starch 6% 130/0.4 compared with gelatin on microvascular reactivity. AB - We compared the effects on microvascular reactivity of hydroxyethylstarch (Volulyte((r)) ) and gelatin (Geloplasma((r)) ) during acute haemodilution. The hypothesis was that Volulyte would provide better microvascular reactivity than Geloplasma. Forty patients undergoing elective cardiac surgery were randomly assigned to receive either Volulyte or Geloplasma as the exclusive priming solution of the cardiopulmonary bypass. To evaluate microvascular reactivity, postocclusive reactive hyperaemia was examined before and after cardiopulmonary bypass. Microvascular reactivity assessments included the rate of the occlusion and reperfusion slopes and reperfusion times. After cardiopulmonary bypass, increases in reperfusion time were significantly smaller in the Volulyte group (3 (-27 to 9 [-35 to 33]%) vs 29 (-17 to 76 [-34 to 137]%) in the Geloplasma group, p = 0.02 between groups). Rate of reperfusion increased in the Volulyte group (26 (-17 to 43 [-59 to 357])%), whereas it decreased in the Geloplasma group (-22 ( 47 to 16 [-84 to 113])%), p = 0.02 between groups. The shorter reperfusion times and increased reperfusion rate suggest that Volulyte maintains better microvascular reactivity than Geloplasma. PMID- 26879008 TI - Five-year changes in soil organic carbon and total nitrogen in coastal wetlands affected by flow-sediment regulation in a Chinese delta. AB - Changes in the sources and sinks of soil organic carbon (SOC) and total nitrogen (TN) in wetland soils as indicators of soil quality and climate change have received attention worldwide. Soil samples were collected in 2007 and 2012 in the coastal wetlands of the Yellow River Delta and the SOC and TN were determined to investigate a five-year change in their content and stock in these wetlands as affected by flow-sediment regulation. Our results revealed that the soils in 2007 exhibited greater electrical conductivities, SOC content and density, and ammonium nitrogen (NH4(+)-N) levels in the top 10 cm soils (p < 0.05) compared with the soils in 2012. In general, the SOC and TN contents decreased with increasing soil depth. However, the highest ratios of soil organic carbon and total nitrogen (molar C/N ratios) were observed in the 30-40 cm soil layer. A significant SOC loss occurred (p < 0.05) in top 10 cm soils, but only a small change in SOC in the top 50 cm soils. Comparatively, TN levels did not show significant differences in the study period. PMID- 26879009 TI - Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson's Disease. AB - BACKGROUND: Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD. METHODS: The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis. RESULTS: Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey-Osterrieth complex figure (copy) results. CONCLUSIONS: When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms. PMID- 26879010 TI - Establishing a Customized Guide Plate for Osteotomy in Total Knee Arthroplasty Using Lower-extremity X-ray and Knee Computed Tomography Images. AB - BACKGROUND: The conventional method cannot guarantee the precise osteotomies required for a perfect realignment and a better prognosis after total knee arthroplasty (TKA). This study investigated a customized guide plate for osteotomy placement in TKAs with the aid of the statistical shape model technique using weight-bearing lower-extremity X-rays and computed tomography (CT) images of the knee. METHODS: From October 2014 to June 2015, 42 patients who underwent a TKA in Guizhou Provincial People's Hospital were divided into a guide plate group (GPG, 21 cases) and a traditional surgery group (TSG, 21 cases) using a random number table method. In the GPG group, a guide plate was designed and printed using preoperative three-dimensional measurements to plan and digitally simulate the operation. TSG cases were treated with the conventional method. Outcomes were obtained from the postoperative image examination and short-term follow-up. RESULTS: Operative time was 49.0 +/- 10.5 min for GPG, and 62.0 +/- 9.7 min in TSG. The coronal femoral angle, coronal tibial angle, posterior tibial slope, and the angle between the posterior condylar osteotomy surface and the surgical transepicondylar axis were 89.2 +/- 1.7 degrees , 89.0 +/- 1.1 degrees , 6.6 +/- 1.4 degrees , and 0.9 +/- 0.3 degrees in GPG, and 86.7 +/- 2.9 degrees , 87.6 +/ 2.1 degrees , 8.9 +/- 2.8 degrees , and 1.7 +/- 0.8 degrees in TSG, respectively. The Hospital for Special Surgery scores 3 months after surgery were 83.7 +/- 18.4 in GPG and 71.5 +/- 15.2 in TSG. Statistically significant differences were found between GPG and TSG in all measurements. CONCLUSIONS: A customized guide plate to create an accurate osteotomy in TKAs may be created using lower-extremity X-ray and knee CT images. This allows for shorter operative times and better postoperative alignment than the traditional surgery. Application of the digital guide plate may also result in better short-term outcomes. PMID- 26879011 TI - Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease. AB - BACKGROUND: Chronic kidney disease (CKD) has become a public health problem. New interventions to slow or prevent disease progression are urgently needed. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of embryonic stem cells (ESCs) on the progression of CKD. METHODS: Adult male Sprague-Dawley rats were subjected to 5/6 nephrectomy. We used pedicled greater omentum flaps packing ESC-loaded gelatin microcryogels (GMs) on the 5/6 nephrectomized kidney. The viability of ESCs within the GMs was detected using in vitro two-photon fluorescence confocal imaging. Rats were sacrificed after 12 weeks. Renal injury was evaluated using serum creatinine, urea nitrogen, 24 h protein, renal pathology, and tubular injury score results. Structural damage was evaluated by periodic acid-Schiff and Masson trichrome staining. RESULTS: In vitro, ESCs could be automatically loaded into the GMs. Uniform cell distribution, good cell attachment, and viability were achieved from day 1 to 7 in vitro. After 12 weeks, in the pedicled greater omentum flaps packing ESC-loaded GMs on 5/6 nephrectomized rats group, the plasma urea nitrogen levels were 26% lower than in the right nephrectomy group, glomerulosclerosis index was 62% lower and tubular injury index was 40% lower than in the 5/6 nephrectomized rats group without GMs. CONCLUSIONS: In a rat model of established CKD, we demonstrated that the pedicled greater omentum flaps packing ESC-loaded GMs on the 5/6 nephrectomized kidney have a long-lasting therapeutic rescue function, as shown by the decreased progression of CKD and reduced glomerular injury. PMID- 26879012 TI - Is Laparoscopic Hepatectomy a Safe, Feasible Procedure in Patients with a Previous Upper Abdominal Surgery? AB - BACKGROUND: Laparoscopic liver resection has become an accepted treatment for liver tumors or intrahepatic bile duct stones, but its application in patients with previous upper abdominal surgery is controversial. The aim of this study was to evaluate the feasibility and safety of laparoscopic hepatectomy in these patients. METHODS: Three hundred and thirty-six patients who underwent laparoscopic hepatectomy at our hospital from March 2012 to June 2015 were enrolled in the retrospective study. They were divided into two groups: Those with previous upper abdominal surgery (PS group, n = 42) and a control group with no previous upper abdominal surgery (NS group, n = 294). Short-term outcomes including operating time, blood loss, hospital stay, morbidity, and mortality were compared among the groups. RESULTS: There was no significant difference in median operative duration between the PS group and the NS group (180 min vs. 160 min, P = 0.869). Median intraoperative blood loss was same between the PS group and the control group (200 ml vs. 200 ml, P = 0.907). The overall complication rate was significantly lower in the NS group than in the PS group (17.0% vs. 31.0%, P = 0.030). Mortality and other short-term outcomes did not differ significantly between groups. CONCLUSIONS: Our study showed no significant difference between the PS group and NS group in term of short-term outcomes. Laparoscopic hepatectomy is a feasible and safe procedure for patients with previous upper abdominal surgery. PMID- 26879013 TI - Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM. AB - BACKGROUND: Lung cancer has become the leading cause of death in many regions. Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes. The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM. METHODS: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations. In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer related genes were also detected by polymerase chain reaction (PCR). RESULTS: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19. Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations. CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p13.31-13.33 and 17p13.1-13.3. And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG). CONCLUSIONS: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis. We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22 23, 9p21-24, 10q25-26.3, 12p13.31-13.33, and 17p13.1-13.3. Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM. PMID- 26879015 TI - Comparative Study of Plasma Endotoxin with Procalcitonin Levels in Diagnosis of Bacteremia in Intensive Care Unit Patients. AB - BACKGROUND: Both procalcitonin (PCT) and plasma endotoxin levels cannot be solely used for a definite diagnosis of bacteremia or sepsis, and there has been few study comparing the values of the two biomarkers for the diagnosis of bacteremia. The aim of this study was to identify bacteria causing bacteremia and evaluate the role of the two biomarkers in the diagnosis of bacteremia in Intensive Care Unit (ICU). METHODS: The medical records of 420 patients in ICU were retrospectively reviewed. Patients (n = 241) who met the inclusion criteria were subjected to blood culture (BC) for the analysis of the endotoxin or PCT levels. The exclusion criteria included the presence of infection with human immunodeficiency virus and/or AIDS, neutropenia without sepsis, pregnancy, treatment with immunosuppressive therapies, or blood diseases such as hematological tumors. Patients' BC episodes were divided into BC negative, Gram negative (GN) bacteria, Gram-positive bacteria, and fungi groups. The PCT and plasma endotoxin levels were compared in the different groups. RESULTS: A total of 241 patients with 505 episodes of BC were analyzed. The GN bacteria group showed higher levels of PCT and endotoxin than the BC negative, Gram-positive bacteria, and fungi groups. GN bacteremia was more prevalent than Gram-positive bacteremia. The GN bacteremia caused by non-Enterobacteriaceae infection presented higher endotoxin level than that by Enterobacteriaceae, but no significant difference in PCT levels was observed between the two groups. The plasma endotoxin significantly differed among different groups and was bacterial species dependent. CONCLUSIONS: Plasma endotoxin was more related to GN than to Gram-positive bacteremia, and that endotoxin level was species dependent, but PCT level remained relatively more stable within the GN bacteria caused bacteremia. Both GN and positive bacteria caused bacteremia in the ICU patients in different regions of China. And PCT is a more valuable biomarker than endotoxin in the diagnosis of bacteremia. PMID- 26879014 TI - Changes in the Bispectral Index in Response to Loss of Consciousness and No Somatic Movement to Nociceptive Stimuli in Elderly Patients. AB - BACKGROUND: Bispectral index (BIS) is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil. METHODS: This study was performed on 52 elderly patients (aged 65-78 years) and 52 young patients (aged 25-58 years), American Society of Anesthesiologists physical status I or II. Anesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, [TENS]) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil predicted effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated. RESULTS: BISLOCin elderly group was higher than that in young patient group (65.4 +/- 9.7 vs. 57.6 +/- 12.3) (t = 21.58, P < 0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6 +/- 0.3 MUg/ml in elderly patients, which was significantly lower than that in young patients (2.3 +/- 0.5 MUg/ml) (t = 7.474, P < 0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t = 8.902 and t = 8.019, P < 0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOSwas the same as the BISLOCin elderly patients (65.6 +/- 10.7 vs. 65.4 +/- 9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS. CONCLUSION: In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually. TRIAL REGISTRATION: CTRI Reg. No: ChiCTR-OOC-14005629; http://www.chictr.org.cn/showproj.aspx?proj=9875. PMID- 26879016 TI - Mechanism of Regulatory Effect of MicroRNA-206 on Connexin 43 in Distant Metastasis of Breast Cancer. AB - BACKGROUND: MicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer. It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer. METHODS: Using quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231). MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed. Cell counting kit 8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity. The mutant plasmids of Cx43-3' untranslated region (3'UTR) at position 478-484 and position 1609-1615 were constructed. Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43. RESULTS: Cx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression. MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor. Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR 206 and Cx43 expression (P = 0.03). MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3'UTR, suggesting that Cx43-3'UTR may be the key in Cx43 regulated by miR-206. Luciferase expression showed that the inhibition efficiency was reduced by 46.80% in position 478-484 mutant, 16.72% in position 1609-1615 mutant; the inhibition was totally disappeared in double mutant (P = 0.02). CONCLUSIONS: MiR-206 can regulate the expression of Cx43, the cytobiological activity, and the metastasis of breast cancer through binding to the two binding sites in Cx43-3'UTR: position 478-484 and position 1609-1615. PMID- 26879017 TI - Preoperative Corticosteroid Usage and Hypoalbuminemia Increase Occurrence of Short-term Postoperative Complications in Chinese Patients with Ulcerative Colitis. AB - BACKGROUND: Clarifying the risk factors for postoperative complications and taking measures to minimize these complications will improve the outcomes in patients with ulcerative colitis (UC). This study aimed to systemically explore the risk factors for short-term postoperative complications in Chinese UC patients undergoing ileocolorectal surgery. METHODS: Forty-nine UC patients undergoing proctocolectomy or ileostomy were retrospectively enrolled. Univariate and multivariate logistic regression analyses were conducted to reveal the risk factors among the clinical, laboratory, and surgical variables as well as preoperative medications. RESULTS: Twenty-two (44.9%) patients who suffered from at least one short-term postoperative event had more severe hypoalbuminemia (P = 0.007) and an increased prevalence of preoperative corticosteroid usage (prednisone more than 20 mg daily or equivalent) for more than 6 weeks (59.1% vs. 25.9%, P = 0.023) compared with patients without short-term postoperative complications. Based on the multivariate logistic regression analysis, the odds ratio (95% confidence interval) values of these two risk factors were 1.756 (0.889-3.470, P = 0.105) and 3.233 (0.916-11.406, P = 0.068), respectively. In 32 severe UC patients, prolonged preoperative hospital stay worsened the short-term postoperative outcomes. CONCLUSIONS: Preoperative corticosteroids usage and hypoalbuminemia worsened the short-term outcomes following ileocolorectal surgery in Chinese UC patients. PMID- 26879018 TI - Tongxinluo Reverses the Hypoxia-suppressed Claudin-9 in Cardiac Microvascular Endothelial Cells. AB - BACKGROUND: Claudin-5, claudin-9, and claudin-11 are expressed in endothelial cells to constitute tight junctions, and their deficiency may lead to hyperpermeability, which is the initiating process and pathological basis of cardiovascular disease. Although tongxinluo (TXL) has satisfactory antianginal effects, whether and how it modulates claudin-5, claudin-9, and claudin-11 in hypoxia-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been reported. METHODS: In this study, HCMECs were stimulated with CoCl2to mimic hypoxia and treated with TXL. First, the messenger RNA (mRNA) expression of claudin-5, claudin-9, and claudin-11 was confirmed. Then, the protein content and distribution of claudin-9, as well as cell morphological changes were evaluated after TXL treatment. Furthermore, the distribution and content histone H3K9 acetylation (H3K9ac) in the claudin-9 gene promoter, which guarantees transcriptional activation, were examined to explore the underlying mechanism, by which TXL up-regulates claudin-9 in hypoxia-stimulated HCMECs. RESULTS: We found that hypoxia-suppressed claudin-9 gene expression in HCMECs (F = 7.244; P = 0.011) and the hypoxia-suppressed claudin-9 could be reversed by TXL (F = 61.911; P = 0.000), which was verified by its protein content changes (F = 29.142; P = 0.000). Moreover, high-dose TXL promoted the cytomembrane localization of claudin 9 in hypoxia-stimulated HCMECs, with attenuation of cell injury. Furthermore, high-dose TXL elevated the hypoxia-inhibited H3K9ac in the claudin-9 gene promoter (F = 37.766; P = 0.000), activating claudin-9 transcription. CONCLUSIONS: The results manifested that TXL reversed the hypoxia-suppressed claudin-9 by elevating H3K9ac in its gene promoter, playing protective roles in HCMECs. PMID- 26879019 TI - The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator. AB - OBJECTIVE: This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (beta2M), a conservative immune molecule in vertebrate. DATA SOURCES: The data used in this review were obtained from PubMed up to October 2015. Terms of beta2M, immune response, and infection were used in the search. STUDY SELECTIONS: Articles related to beta2M were retrieved and reviewed. Articles focusing on the characteristic and function of beta2M were selected. The exclusion criteria of articles were that the studies on beta2M related molecules. RESULTS: beta2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of beta2M is associated with multiple diseases, including endogenous and infectious diseases. beta2M could directly participate in the development of cancer cells, and the level of beta2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis. CONCLUSIONS: Based on the characteristic of beta2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, beta2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of beta2M on applications. PMID- 26879020 TI - Autophagy in 5-Fluorouracil Therapy in Gastrointestinal Cancer: Trends and Challenges. AB - OBJECTIVE: 5-Fluorouracil (5-FU)-based combination therapies are standard treatments for gastrointestinal cancer, where the modulation of autophagy is becoming increasingly important in offering effective treatment for patients in clinical practice. This review focuses on the role of autophagy in 5-FU-induced tumor suppression and cancer therapy in the digestive system. DATA SOURCES: All articles published in English from 1996 to date those assess the synergistic effect of autophagy and 5-FU in gastrointestinal cancer therapy were identified through a systematic online search by use of PubMed. The search terms were "autophagy" and "5-FU" and ("colorectal cancer" or "hepatocellular carcinoma" or "pancreatic adenocarcinoma" or "esophageal cancer" or "gallbladder carcinoma" or "gastric cancer"). STUDY SELECTION: Critical reviews on relevant aspects and original articles reporting in vitro and/or in vivo results regarding the efficiency of autophagy and 5-FU in gastrointestinal cancer therapy were reviewed, analyzed, and summarized. The exclusion criteria for the articles were as follows: (1) new materials (e.g., nanomaterial)-induced autophagy; (2) clinical and experimental studies on diagnostic and/or prognostic biomarkers in digestive system cancers; and (3) immunogenic cell death for anticancer chemotherapy. RESULTS: Most cell and animal experiments showed inhibition of autophagy by either pharmacological approaches or via genetic silencing of autophagy regulatory gene, resulting in a promotion of 5-FU-induced cancer cells death. Meanwhile, autophagy also plays a pro-death role and may mediate cell death in certain cancer cells where apoptosis is defective or difficult to induce. The dual role of autophagy complicates the use of autophagy inhibitor or inducer in cancer chemotherapy and generates inconsistency to an extent in clinic trials. CONCLUSION: Autophagy might be a therapeutic target that sensitizes the 5 FU treatment in gastrointestinal cancer. PMID- 26879022 TI - How to Initiate and Perform Simulation-based Airway Management Training More Effectively and Efficiently in China? PMID- 26879023 TI - Idiopathic Basal Ganglia Calcification Presented with Progressive Supranuclear Palsy-like Features. PMID- 26879021 TI - Evolving Molecular Genetics of Glioblastoma. AB - OBJECTIVE: To summary the recent advances in molecular research of glioblastoma (GBM) and current trends in personalized therapy of this disease. DATA SOURCES: Data cited in this review were obtained mainly from PubMed in English up to 2015, with keywords "molecular", "genetics", "GBM", "isocitrate dehydrogenase", "telomerase reverse transcriptase", "epidermal growth factor receptor", "PTPRZ1 MET", and "clinical treatment". STUDY SELECTION: Articles regarding the morphological pathology of GBM, the epidemiology of GBM, genetic alteration of GBM, and the development of treatment for GBM patients were identified, retrieved, and reviewed. RESULTS: There is a large amount of data supporting the view that these recurrent genetic aberrations occur in a specific context of cellular origin, co-oncogenic hits and are present in distinct patient populations. Primary and secondary GBMs are distinct disease entities that affect different age groups of patients and develop through distinct genetic aberrations. These differences are important, especially because they may affect sensitivity to radio- and chemo-therapy and should thus be considered in the identification of targets for novel therapeutic approaches. CONCLUSION: This review highlights the molecular and genetic alterations of GBM, indicating that they are of potential value in the diagnosis and treatment for patients with GBM. PMID- 26879024 TI - Reversible Posterior Leukoencephalopathy Syndrome Sometimes Could be Irreversible: A Case Following Tumor Lysis Syndrome in Childhood Burkitt's Lymphoma. PMID- 26879025 TI - Uterine Artery Rupture After Induced Abortion and Extraction of an Intrauterine Device. PMID- 26879026 TI - Myotonic Dystrophy Type 1 with Syringomyelia in a Young Patient. PMID- 26879027 TI - Small Bowel Obstruction Secondary to Obturator Hernia Preoperatively Diagnosed by Ultrasound. PMID- 26879028 TI - New "P" in Medical Model. PMID- 26879029 TI - Unilateral Internal Carotid Artery Occlusion After Letrozole Treatment in a Postmenopausal Woman with Breast Cancer. PMID- 26879030 TI - A Rare Case of Carotid Body Tumor Presenting with Internal Carotid Artery Blood Supply and Carotid Sinus Syndrome. PMID- 26879031 TI - Thunderclap Headache Caused by an Inadvertent Epidural Puncture During Oxygen ozone Therapy for Patient with Cervical Disc Herniation. PMID- 26879032 TI - After Administration of Intravenous Epinephrine for bee Sting-induced Anaphylaxis: Kounis Syndrome or Epinephrine Effect? PMID- 26879033 TI - Comparing Sedation Regimens for Awake Fiberoptic Intubation. PMID- 26879034 TI - Authors' Reply to Letter to the Editor "Comparing Sedation Regimens for Awake Fiberoptic Intubation". PMID- 26879035 TI - Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system. AB - CONTEXT: Cardiotoxicity and myelosuppression of etoposide (ETP) limited its clinical application. Targeted drug delivery system could deliver anticancer agents to the target cancerous cells, thus reducing their toxicity. OBJECTIVE: In this study, folate (FA) was applied for the construction of nanostructured lipid carriers (NLCs), and used for targeted delivery of ETP to tumors overexpresses the FA receptors. METHODS: FA-poly (ethylene glycol) distearoylphosphatidylethanolamine was synthesized. FA decorated and ETP-loaded NLCs (FA-ETP-NLCs) were prepared and the formulation was optimized by Box-Behnken design. Their particle size (PS), zeta potential and drug encapsulation efficiency (EE) was evaluated. In vitro cytotoxicity studies of FA-ETP-NLCs were tested in CT26, SGC7901, NCI-H209 cell lines. In vivo antitumor efficacies of the carriers were evaluated on mice bearing CT26 cells xenografts. RESULTS: The optimum FA-ETP-NLCs formulations had a PS of 120.86 nm. The growth of CT26, SGC790 or NCI-H209 cells in vitro was obviously inhibited. FA-ETP-NLCs also displayed the best antitumor activity than other formulations in vivo. CONCLUSION: The results demonstrated that FA-ETP-NLCs were efficient in selective delivery to CT26, SGC790 or NCI-H209 cells overexpressing the FA receptors. Also, FA-ETP-NLCs can sufficiently transfer ETP to the cancer cells, enhance the antitumor capacity. Thus, FA-ETP-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy. PMID- 26879036 TI - A randomized trial of a pain management intervention for adults receiving substance use disorder treatment. AB - BACKGROUND AND AIMS: Chronic pain is difficult to treat in individuals with substance use disorders and, when not resolved, can have a negative impact on substance use disorder treatment outcomes. This study tested the efficacy of a psychosocial pain management intervention, ImPAT (improving pain during addiction treatment), that combines pain management with content related to managing pain without substance use. DESIGN: Single-site, parallel-groups randomized controlled trial comparing ImPAT to a supportive psychoeducational control (SPC) condition; follow-up assessments occurred at 3, 6 and 12 months. SETTING: The Ann Arbor VA Substance Use Disorder treatment program, USA. PARTICIPANTS: Veterans Health Administration patients {n = 129; mean [standard deviation (SD)], age = 51.7 (9.5); 115 of 129 (89%) male; ImPAT (n = 65); SPC (n = 64)}. INTERVENTION: ImPAT combines principles of cognitive-behavioral therapy and acceptance-based approaches to pain management with content related to avoiding the use of substances as a coping mechanism for pain. The SPC used a psychoeducational attention control treatment for alcoholism modified to cover other substances in addition to alcohol. MEASUREMENTS: Primary: Pain intensity over 12 months; secondary: pain-related functioning, frequency of alcohol and drug use over 12 months. FINDINGS: Primary: randomization to the ImPAT intervention versus SPC predicted significantly lower pain intensity {beta [standard error (SE)] = -0.71 (0.29); 95% confidence interval (CI) = -1.29, -0.12}; secondary: relative to the SPC condition, those who received ImPAT also reported improved pain-related functioning [beta (SE) = 0.27 (0.11); 95% CI = 0.05, 0.49] and lower frequency of alcohol consumption [beta (SE) = -0.77; 95% CI = -1.34, -0.20]. No differences were found between conditions on frequency of drug use over follow-up. CONCLUSIONS: For adults with pain who are enrolled in addictions treatment, receipt of a psychological pain management intervention (improving pain during addiction treatment) reduced pain and alcohol use and improves pain-related functioning over 12 months relative to a matched-attention control condition. PMID- 26879037 TI - Limits to preference and the sensitivity of choice to rate and amount of food. AB - Studies of choice holding food-amount ratio constant while varying food-rate ratio within sessions showed that local changes in preference depend on relative amount of food. The present study investigated whether sensitivity of choice to food-rate ratio and sensitivity to food-amount ratio are independent of one another when food-rate ratios are varied across sessions and food-amount ratios are varied within sessions. Food deliveries for rats' presses on the left and right levers were scheduled according to three different food-rate ratios of 1:1, 9:1, and 1:9; each food-rate ratio lasted for 106 sessions and was arranged independently of seven food-amount ratios (7:1, 6:2, 5:3, 4:4, 3:5, 2:6, and 1:7 food pellets) occurring within sessions in random sequence. Each amount ratio lasted for 10 food deliveries and was separated from another by a 60-s blackout. Sensitivity to rate ratio was high (1.0) across food deliveries. Sensitivity to amount ratio was low when food rates were equal across alternatives, but was high when rate ratio and amount ratio opposed one another. When rate ratio and amount ratio went in the same direction, choice ratio reached an elevenfold limit which reduced sensitivity to approximately zero. We conclude that three factors affect sensitivity to amount: (1) the limit to preference, (2) the equal effect on preference of amounts greater than four pellets, and (3) the absence of differential effects of switches in amount in the equal-rates (1:1) condition. Taken together, these findings indicate that rate and amount only sometimes combine independently as additive variables to determine preference when amount ratios vary frequently within sessions. PMID- 26879039 TI - Quantitative assessment of the serve speed in tennis. AB - A method is presented for assessing the serve speeds of tennis players based on their body height. The research involved a sample of top world players (221 males and 215 females) who participated in the Grand Slam tournaments in 2008 and 2012. The method is based on the linear regression analysis of the association between the player's body height and the serve speed (fastest serve, average first-serve, and second-serve speed). The coefficient of serve speed (CSS) was calculated as the quotient of the measured and the theoretical value of the serve speed on a regression line relative to the player's body height. The CSS of >1, 1 and <1 indicate above-average, average, and below-average serve speeds, respectively, relative to the top world tennis players with the same body height. The CSS adds a new element to the already existing statistics about a tennis match, and provides additional information about the performance of tennis players. The CSS can be utilised e.g. for setting the target serve speed of a given player to achieve based on his/her body height, choosing the most appropriate match strategy against a particular player, and a long-term monitoring of the effectiveness of training focused on the serve speed. PMID- 26879038 TI - C3'-Deoxygenation of Paromamine Catalyzed by a Radical S-Adenosylmethionine Enzyme: Characterization of the Enzyme AprD4 and Its Reductase Partner AprD3. AB - C3'-deoxygenation of aminoglycosides results in their decreased susceptibility to phosphorylation thereby increasing their efficacy as antibiotics. However, the biosynthetic mechanism of C3'-deoxygenation is unknown. To address this issue, aprD4 and aprD3 genes from the apramycin gene cluster in Streptomyces tenebrarius were expressed in E. coli and the resulting gene products were characterized in vitro. AprD4 is shown to be a radical S-adenosylmethionine (SAM) enzyme, catalyzing homolysis of SAM to 5'-deoxyadenosine (5'-dAdo) in the presence of paromamine. [4'-(2) H]-Paromamine was prepared and used to show that its C4'-H is transferred to 5'-dAdo by AprD4, during which the substrate is dehydrated to a product consistent with 4'-oxolividamine. In contrast, paromamine is reduced to a deoxy product when incubated with AprD4/AprD3/NADPH. These results show that AprD4 is the first radical SAM diol-dehydratase and, along with AprD3, is responsible for 3'-deoxygenation in aminoglycoside biosynthesis. PMID- 26879040 TI - Negative shadows conveying a positive note. PMID- 26879041 TI - The PAediatric Risk Assessment (PARA) Mobile App to Reduce Postdischarge Child Mortality: Design, Usability, and Feasibility for Health Care Workers in Uganda. AB - BACKGROUND: Postdischarge death in children is increasingly being recognized as a major contributor to overall child mortality. The PAediatric Risk Assessment (PARA) app is an mHealth tool developed to aid health care workers in resource limited settings such as Sub-Saharan Africa to identify pediatric patients at high risk of both in-hospital and postdischarge mortality. The intended users of the PARA app are health care workers (ie, nurses, doctors, and clinical officers) with varying levels of education and technological exposure, making testing of this clinical tool critical to successful implementation. OBJECTIVE: Our aim was to summarize the usability evaluation of the PARA app among target users, which consists of assessing the ease of use, functionality, and navigation of the interfaces and then iteratively improving the design of this clinical tool. METHODS: Health care workers (N=30) were recruited to participate at Mbarara Regional Referral Hospital and Holy Innocents Children's Hospital in Mbarara, Southwestern Uganda. This usability study was conducted in two phases to allow for iterative improvement and testing of the interfaces. The PARA app was evaluated using quantitative and qualitative measures, which were compared between Phases 1 and 2 of the study. Participants were given two patient scenarios that listed hypothetical information (ie, demographic, social, and clinical data) to be entered into the app and to determine the patient's risk of in-hospital and postdischarge mortality. Time-to-completion and user errors were recorded for each participant while using the app. A modified computer system usability questionnaire was utilized at the end of each session to elicit user satisfaction with the PARA app and obtain suggestions for future improvements. RESULTS: The average time to complete the PARA app decreased by 30% from Phase 1 to Phase 2, following user feedback and modifications. Participants spent the longest amount of time on the oxygen saturation interface, but modifications following Phase 1 cut this time by half. The average time-to-completion (during Phase 2) for doctors/medical students was 3 minutes 56 seconds. All participants agreed they would use the PARA app if available at their health facility. Given a high PARA risk score, participants suggested several interventions that would be appropriate for the sociocultural context in southwestern Uganda, which involved strengthening discharge and referral procedures within the current health care system. CONCLUSIONS: Through feedback and modifications made during this usability study, the PARA app was developed into a user-friendly app, encompassing user expectations and culturally intuitive interfaces for users with a range of technological exposure. Doctors and medical students had shorter task completion times, though all participants reported the usefulness of this tool to improve postdischarge outcomes. PMID- 26879042 TI - Small protein domains fold inside the ribosome exit tunnel. AB - Cotranslational folding of small protein domains within the ribosome exit tunnel may be an important cellular strategy to avoid protein misfolding. However, the pathway of cotranslational folding has so far been described only for a few proteins, and therefore, it is unclear whether folding in the ribosome exit tunnel is a common feature for small protein domains. Here, we have analyzed nine small protein domains and determined at which point during translation their folding generates sufficient force on the nascent chain to release translational arrest by the SecM arrest peptide, both in vitro and in live E. coli cells. We find that all nine protein domains initiate folding while still located well within the ribosome exit tunnel. PMID- 26879044 TI - Artificial tongue based on metal-biomolecule coordination polymer nanoparticles. AB - We construct an array-based recognition system (the so-called artificial tongue) through the self-assembly of nucleotides, dyes and lanthanide ions. Metal ions are selected as model analytes for verifying its discrimination ability. The work provides valuable insights into the application and development of biomolecule based materials. PMID- 26879043 TI - Allosteric coupling between proximal C-terminus and selectivity filter is facilitated by the movement of transmembrane segment 4 in TREK-2 channel. AB - TREK-2, a member of two-pore-domain potassium channel family, regulates cellular excitability in response to diverse stimuli. However, how such stimuli control channel function remains unclear. Here, by characterizing the responses of cytosolic proximal C-terminus deletant (DeltapCt) and transmembrane segment 4 (M4)-glycine hinge mutant (G312A) to 2-Aminoethoxydiphenyl borate (2-APB), an activator of TREK-2, we show that the transduction initiated from pCt domain is allosterically coupled with the conformation of selectivity filter (SF) via the movements of M4, without depending on the original status of SF. Moreover, DeltapCt and G312A also exhibited blunted responses to extracellular alkalization, a model to induce SF conformational transition. These results suggest that the coupling between pCt domain and SF is bidirectional, and M4 movements are involved in both processes. Further mechanistic exploration reveals that the function of Phe316, a residue close to the C-terminus of M4, is associated with such communications. However, unlike TREK-2, M4-hinge of TREK-1 only controls the transmission from pCt to SF, rather than SF conformational changes triggered by pHo changes. Together, our findings uncover the unique gating properties of TREK-2, and elucidate the mechanisms for how the extracellular and intracellular stimuli harness the pore gating allosterically. PMID- 26879045 TI - An exploration of the correlates of nurse practitioners' clinical decision-making abilities. AB - AIMS AND OBJECTIVES: This study investigated nurse practitioners' clinical decision-making abilities and the factors that affect these abilities. BACKGROUND: Nurse practitioners play an important role in clinical care decision making; however, studies exploring the factors that affect their decision-making abilities are lacking. DESIGN: A cross-sectional descriptive survey was employed. METHODS: A purposive sample of 197 nurse practitioners was recruited from a medical centre in central Taiwan. Structured questionnaires consisting of the Knowledge Readiness Scale, the Critical Thinking Disposition Inventory and the Clinical Decision-Making Model Inventory were used to collect data. RESULTS: The intuitive-analytical type was the most commonly used decision-making model, and the intuitive type was the least frequently used model. The decision-making model used was significantly related to the nurse practitioners' work unit. Significant differences were noted between the nurse practitioners' clinical decision-making models and their critical thinking dispositions (openness and empathy). The nurse practitioners' years of work experience, work unit, professional knowledge and critical thinking disposition (openness and empathy as well as holistic and reflective dispositions) predicted the nurse practitioners' analytical decision making scores. Age, years of nurse practitioner work experience, work unit and critical thinking disposition (holistic and reflective) predicted the nurse practitioners' intuitive decision-making scores. CONCLUSIONS: This study contributes to the topic of clinical decision-making by describing various types of nurse practitioner decision-making. The factors associated with analytic and intuitive decision-making scores were identified. These findings might be beneficial when planning continuing education programmes to enhance the clinical decision-making abilities of nurse practitioners. RELEVANCE TO CLINICAL PRACTICE: The study results showed that nurse practitioners demonstrated various clinical decision-making types across different work units. Consideration of nurse practitioners' knowledge readiness and their specific needs while planning on duty education programmes is necessary. PMID- 26879046 TI - Isolated tumor cells in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. AB - BACKGROUND: Lymph node (LN) involvement represents the strongest prognostic factor in colon cancer patients. The objective of this prospective study was to assess the prognostic impact of isolated tumor cells (ITC, defined as cell deposits <= 0.2 mm) in loco-regional LN of stage I & II colon cancer patients. METHODS: Seventy-four stage I & II colon cancer patients were prospectively enrolled in the present study. LN at high risk of harboring ITC were identified via an in vivo sentinel lymph node procedure and analyzed with multilevel sectioning, conventional H&E and immunohistochemical CK-19 staining. The impact of ITC on survival was assessed using Cox regression analyses. RESULTS: Median follow-up was 4.6 years. ITC were detected in locoregional lymph nodes of 23 patients (31.1%). The presence of ITC was associated with a significantly worse disease-free survival (hazard ratio = 4.73, p = 0.005). Similarly, ITC were associated with significantly worse overall survival (hazard ratio = 3.50, p = 0.043). CONCLUSIONS: This study provides compelling evidence that ITC in stage I & II colon cancer patients are associated with significantly worse disease-free and overall survival. Based on these data, the presence of ITC should be classified as a high risk factor in stage I & II colon cancer patients who might benefit from adjuvant chemotherapy. PMID- 26879047 TI - Resting-state functional connectivity between the dorsal anterior cingulate cortex and thalamus is associated with risky decision-making in nicotine addicts. AB - Nicotine addiction is associated with risky behaviors and abnormalities in local brain areas related to risky decision-making such as the dorsal anterior cingulate cortex (dACC), anterior insula (AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. However, it is unclear whether circuit-level abnormalities lead to risky decision-making in smokers. In the current study, we used task-based functional magnetic resonance imaging (fMRI) and examined resting-state functional connectivity (RSFC) to study how connectivity between the dACC, insula, and thalamus influence risky decision-making in nicotine addicts. We found that an increase in risky decision-making was associated with stronger nicotine dependence and stronger RSFC of the dACC-rAI (right AI), the dACC-thalamus, the dACC-lAI (left AI), and the rAI-lAI, but that risky decision-making was not associated with risk level-related activation. Furthermore, the severity of nicotine dependence positively correlated with RSFC of the dACC-thalamus but was not associated with risk level-related activation. Importantly, the dACC-thalamus coupling fully mediated the effect of nicotine-dependent severity on risky decision-making. These results suggest that circuit-level connectivity may be a critical neural link between risky decision-making and severity of nicotine dependence in smokers. PMID- 26879049 TI - Long-term outcomes of a phase II randomized controlled trial comparing intensity modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma. AB - BACKGROUND: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment outcomes. We conducted a phase II randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC. METHODS: Between April 2002 and January 2008, 69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group (n = 35). All patients received intensity-modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23 53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m(2) by intravenous infusion weekly during radiotherapy. RESULTS: The median follow-up period of all patients was 35 months (range 2-112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3-year and 5-year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3-4 (33.0% vs. 13.2%, P = 0.009), stages III IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%, P = 0.017), and tumor volume >26 cm(3) (37.6% vs. 0%, P = 0.006). CONCLUSION: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3-4) and stage (III-IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm(3). PMID- 26879048 TI - Uncovering the pathways underlying whole body regeneration in a chordate model, Botrylloides leachi using de novo transcriptome analysis. AB - BACKGROUND: Regenerative capacity differs greatly between animals. In vertebrates regenerative abilities are highly limited and tissue or organ specific. However the closest related chordate to the vertebrate clade, Botrylloides leachi, can undergo whole body regeneration (WBR). Therefore, research on WBR in B. leachi has focused on pathways known to be important for regeneration in vertebrates. To obtain a comprehensive vision of this unique process we have carried out the first de novo transcriptome sequencing for multiple stages of WBR occurring in B. leachi. The identified changes in gene expression during B. leachi WBR offer novel insights into this remarkable ability to regenerate. RESULTS: The transcriptome of B. leachi tissue undergoing WBR were analysed using differential gene expression, gene ontology and pathway analyses. We observed up-regulation in the expression of genes involved in wound healing and known developmental pathways including WNT, TGF-beta and Notch, during the earliest stages of WBR. Later in WBR, the expression patterns in several pathways required for protein synthesis, biogenesis and the organisation of cellular components were up regulated. CONCLUSIONS: While the genes expressed early on are characteristic of a necessary wound healing response to an otherwise lethal injury, the subsequent vast increase in protein synthesis conceivably sustains the reestablishment of the tissue complexity and body axis polarity within the regenerating zooid. We have, for the first time, provided a global overview of the genes and their corresponding pathways that are modulated during WBR in B. leachi. PMID- 26879050 TI - Comparison of different polar compounds-induced cytotoxicity in human hepatocellular carcinoma HepG2 cells. AB - Total polar compounds (TPC) formed during successive frying have the negative healthy effects. However, little researches focused on the cytotoxicity of different parts of TPC. The present study was carried out to elucidate the different polar compounds-induced apoptosis in human hepatocellular carcinoma (HCC) HepG2 cells. The polar compounds of frying oil named oxidized triglycerides oligo (TGO), oxidized triglycerides dimer (TGD), and oxidize triglycerides (ox TG) were isolated and collected via HPLC. MTT assay was selected to determine the cell viability, and apoptosis rate of the cells was analyzed with the help of flow cytometry. The results indicated that TGO, TGD, or ox-TG could suppress the proliferation of HepG2 cells and improve the cell apoptosis in the concentration- and time- dependent manner. Different polar compounds have the different activity of cytotoxicity and apoptosis (p < 0.05), and ox-TG was the most serious deleterious on HepG2 cell viability and apoptotic, followed by TGO and TGD. At the concentration of 2.00 mg/ml and incubated for 48 h, the cell inhibition rate and apoptotic rate of HepG2 induced by ox-TG could reach 23.0 % and 16.05 %, respectively. Cell cycle analysis showed that the inhibition of TGO, TGD, and ox TG on HepG2 cells mainly occurred in S phase. PMID- 26879051 TI - Cooperative pain education and self-management (COPES): study design and protocol of a randomized non-inferiority trial of an interactive voice response-based self management intervention for chronic low back pain. AB - BACKGROUND: The Institute of Medicine report "Relieving Pain in America" recommends the promotion of patient self-management of pain for all people with pain. Given the high prevalence of chronic pain in the US, new strategies are needed to enhance access to cognitive behavioral therapy (CBT) and other evidence based treatments designed to facilitate self-management of chronic pain conditions. Although CBT is efficacious, many patients have limited or no access to CBT. Technology-assisted delivery of CBT may improve access while maintaining efficacy. METHODS/DESIGN: We describe a randomized non-inferiority trial of interactive voice response (IVR)-based CBT for patients with chronic low back pain. This intervention uses daily IVR monitoring and weekly pre-recorded therapist feedback, based on patient-reported information, to provide treatment for patients at home. A total of 230 patients with chronic low back pain are being identified from a single statewide health system serving US military veterans. Participants are randomized to receive either ten weeks of in-person CBT or IVR-based CBT. The primary outcome is pain intensity as measured by the Numeric Rating Scale immediately post-treatment. Secondary outcomes include pain related interference, emotional functioning, and quality of life measured immediately post treatment, and 6 and 9 months post recruitment. Exploratory objectives of the study are to examine: (1) potential mediators of impact on clinical outcomes (treatment retention, self-reported skill practice ratings, IVR call adherence, and treatment satisfaction); and (2) moderators of treatment engagement, adherence to therapist recommendations for pain coping skill practice, and effects on clinical outcomes. DISCUSSION: This non-inferiority trial may identify an alternative to resource intensive in-person CBT that allows many more patients to receive care while also increasing retention of those enrolled in the program. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01025752 . Registered 3 December 2009. PMID- 26879052 TI - Screening and managing obstructive sleep apnoea in nocturnal heart block patients: an observational study. AB - BACKGROUND: Nocturnal heart block often occurs in patients with obstructive sleep apnoea (OSA). It is more likely to be undiagnosed in heart block patients who are ignorant of the symptoms of sleep disorder. Berlin Questionnaire (BQ) is a highly reliable way to discover the risk factors of OSA, whereas the validity in sleep related heart block patients is uncertain. We performed an observational study to address these issues and confirmed the potential protective effect of continuous positive airway pressure (CPAP). METHODS: Patients who were previously diagnosed with nocturnal heart block with R-R pauses exceeding 2 seconds were retrospective screened from the ECG centre of Zhongshan hospital. These recruited participants completed Berlin Questionnaire and underwent polysomnography synchronously with 24-hour Holter monitoring. A cross-sectional analysis was performed to confirm the association between nocturnal arrhythmia and OSA, as well as to assess the diagnostic accuracy of the BQ. Subsequently, subjects diagnosed with OSA (apnoea hypopnoea index > 5) underwent 3 consecutive days of CPAP therapy. On the third day, patients repeated 24-hour Holter monitoring within the institution of CPAP. RESULTS: The symptoms of disruptive snoring and hypersomnolence in 72 enrolled patients were more related to the occurrence of nocturnal heart block (r = 0.306, 0.226, respectively, p = 0.015, 0.019) than syncope (r = 0.134, p = 0.282) and palpitations (r = 0.106, p = 0.119), which were prominent trait of our study population. The sensitivity, specificity, positive and negative predictive value of the BQ at a cut-off point of 5 of AHI for detecting OSA in heart block patients was 81.0 %, 44.4 %, 91.07 % and 25 %. Nocturnal heart block does not appear to occur exclusively in severe sleep apnoea. The frequent occurrence of arrhythmias in prominent oxygen desaturation supports the correlation between them. CPAP therapy resulted in significant decrease in the average number of episodes of heart block, from 148.58 +/- 379.44 to 16.07 +/- 58.52 (p < 0.05), same to the change of the longest RR pausing time (from 4.38 +/- 2.95 s to 0.57 +/- 1.05 s, p = 0.169) in 51 patients. The optimal therapy pressure to make the observed arrhythmia disappeared is 12 cm H2O. CONCLUSION: Concerning high prevalence of OSA in heart block patients, BQ provided an economical and efficient screening method for OSA. For better management, CPAP therapy is feasible to prevent heart blocks avoiding unnecessary concomitant pacemaker implantation. PMID- 26879053 TI - Diagnosis of a malayan filariasis case using a shotgun diagnostic metagenomics assay. AB - BACKGROUND: Malayan filariasis is a lymphatic filariasis caused by Brugia malayi. It is easily misdiagnosed in non-endemic areas for atypical symptoms and rare diagnostic experience. A 34-year-old Chinese woman in New York presented with diffuse erythema on her body, swelling of her body, and watery, itchy, red, sore, swollen and stinging of the eyes, and severe night-time itching. No hospital that the patient visited could make a definite diagnosis by conventional diagnostic methods. It is therefore necessary to explore a new effective method to detect the pathogen that infected the patient. FINDINGS: An unbiased metagenomic approach was used in this study. After DNA was extracted from the patient's eye discharge sample and subcutaneous tissue sample, extended parallel sequencing was performed. The obtained raw reads were aligned to human genome to filter out the reads of the host, and the remaining reads were aligned to a candidate pathogenic protein database and four filarial genomes. The result showed that the reads of B. malayi accounted for an overwhelming ratio in the two samples, which indicated that the patient suffered from malayan filariasis. The subsequent therapeutic efficacy of anti-filariasis treatment validated the result of metagenomics assay. CONCLUSIONS: The present study proved that metagenomic assay can be an effective approach in the diagnosis of parasitic infection. We report a rare case of malayan filariasis from the United States. PMID- 26879054 TI - Statistical correlation of nonconservative substitutions of HIV gp41 variable amino acid residues with the R5X4 HIV-1 phenotype. AB - BACKGROUND: The interaction of the envelope glycoprotein of HIV-1 (gp120/gp41) with coreceptor molecules has important implications for specific cellular targeting and pathogenesis. Experimental and theoretical evidences have shown a role for gp41 in coreceptor tropism, although there is no consensus about the positions involved. Here we analyze the association of physicochemical properties of gp41 amino acid residues with viral tropism (X4, R5, and R5X4) using a large set of HIV-1 sequences. Under the assumption that conserved regions define the complex structural features essential for protein function, we focused our search only on amino acids in the gp41 variable regions. METHODS: Gp41 amino acid sequences of 2823 HIV-1 strains from all clades with known coreceptor tropism were retrieved from Los Alamos HIV Database. Consensus sequences were constructed for homologous sequences (those obtained from the same patient and having the same tropism) in order to avoid bias due to sequence overrepresentation, and the variability (entropy) per site was determined. Comparisons of hydropathy index (HI) and charge (Q) of amino acid residues at highly variable positions between coreceptor groups were performed using two non-parametrical tests and Benjamini Hochberg correction. Pearson's correlation analysis was performed to determine covariance of HI and Q values. RESULTS: Calculation of variability per site rendered 58 highly variable amino acid positions. Of these, statistical analysis rendered significantly different HI or Q only for the R5 vs. R5X4 comparison at twelve positions: 535, 602, 619, 636, 640, 641, 658, 662, 667, 723, 756 and 841. The largest differences in particular amino acid frequencies between coreceptor groups were found at 619, 636, 640, 641, 662, 723 and 756. A hydrophobic tendency of residues 619, 640, 641, 723 and 756, along with a hydrophilic/charged tendency at residues 636 and 662 was observed in R5X4 with respect to R5 sequences. HI of position 640 covariated with that of 602, 619, 636, 662, and 756. CONCLUSIONS: Variability and significant correlations of physicochemical properties with viral phenotype suggest that substitutions at residues in the loop (602 and 619), the HR2 (636, 640, 641, 662), and the C-terminal tail (723, 756) of gp41 may contribute to phenotype of R5X4 strains. PMID- 26879055 TI - X-ray Irradiated Vaccine Confers protection against Pneumonia caused by Pseudomonas aeruginosa. AB - Pseudomonas aeruginosa is a gram-negative bacterium and one of the leading causes of nosocomial infection worldwide, however, no effective vaccine is currently available in the market. Here, we demonstrate that inactivation of the bacteria by X-ray irradiation inhibits its replication capability but retained antigenic expression functionally thus allowing its use as a potential vaccine. Mice immunized by this vaccine were challenged by the parental strain, the O-antigen homologous strain PAO-1 (O2/O5) and heterologous strain PAO-6 (O6) in an acute pneumonia model. We further measured the protective effect of the vaccine, as well as host innate and cellular immunity responses. We found immunized mice could protect against both strains. Notably, the antiserum only had significant protective role against similar bacteria, while adoptive transfer of lymphocytes significantly controlled the spread of the virulent heterologous serogroup PAO-6 infection, and the protective role could be reversed by CD4 rather than CD8 antibody. We further revealed that vaccinated mice could rapidly recruit neutrophils to the airways early after intranasal challenge by PAO-6, and the irradiated vaccine was proved to be protective by the generated CD4(+) IL-17(+) Th17 cells. In conclusion, the generation of inactivated but metabolically active microbes is a promising strategy for safely vaccinating against Pseudomonas aeruginosa. PMID- 26879056 TI - Design, Synthesis, and Evaluation of Irciniastatin Analogues: Simplification of the Tetrahydropyran Core and the C(11) Substituents. AB - The design, synthesis, and biological evaluation of irciniastatin A (1) analogues, achieved by removal of three synthetically challenging structural units, as well as by functional group manipulation of the C(11) substituent of both irciniastatins A and B (1 and 2), has been achieved. To this end, we first designed a convergent synthetic route toward the diminutive analogue (+)-C(8) desmethoxy-C(11)-deoxy-C(12)-didesmethylirciniastatin (6). Key transformations include an acid-catalyzed 6-exo-tet pyran cyclization, a chiral Lewis acid mediated aldol reaction, and a facile amide union. The absolute configuration of 6 was confirmed via spectroscopic analysis (CD spectrum, HSQC, COSY, and ROESY NMR experiments). Structure-activity relationship (SAR) studies of 6 demonstrate that the absence of the three native structural units permits access to analogues possessing cytotoxic activity in the nanomolar range. Second, manipulation of the C(11) position, employing late-stage synthetic intermediates from our irciniastatin syntheses, provides an additional five analogues (7-11). Biological evaluation of these analogues indicates a high functional group tolerance at position C(11). PMID- 26879057 TI - Effect of calf purchase and other herd-level risk factors on mortality, unwanted early slaughter, and use of antimicrobial group treatments in Swiss veal calf operations. AB - The objective of this survey was to determine herd level risk factors for mortality, unwanted early slaughter, and metaphylactic application of antimicrobial group therapy in Swiss veal calves in 2013. A questionnaire regarding farm structure, farm management, mortality and antimicrobial use was sent to all farmers registered in a Swiss label program setting requirements for improved animal welfare and sustainability. Risk factors were determined by multivariable logistic regression. A total of 619 veal producers returned a useable questionnaire (response rate=28.5%), of which 40.9% only fattened their own calves (group O), 56.9% their own calves and additional purchased calves (group O&P), and 2.3% only purchased calves for fattening (group P). A total number of 19,077 calves entered the fattening units in 2013, of which 21.7%, 66.7%, and 11.6% belonged to groups O, O&P, and P, respectively. Mortality was 0% in 322 herds (52.0%), between 0% and 3% in 47 herds (7.6%), and >=3% in 250 herds (40.4%). Significant risk factors for mortality were purchasing calves, herd size, higher incidence of BRD, and access to an outside pen. Metaphylaxis was used on 13.4% of the farms (7.9% only upon arrival, 4.4% only later in the fattening period, 1.1% upon arrival and later), in 3.2% of the herds of group O, 17.9% of those in group O&P, and 92.9% of those of group P. Application of metaphylaxis upon arrival was positively associated with purchase (OR=8.9) and herd size (OR=1.2 per 10 calves). Metaphylaxis later in the production cycle was positively associated with group size (OR=2.9) and risk of respiratory disease (OR=1.2 per 10% higher risk) and negatively with the use of individual antimicrobial treatment (OR=0.3). In many countries, purchase and a large herd size are inherently connected to veal production. The Swiss situation with large commercial but also smaller herds with little or no purchase of calves made it possible to investigate the effect of these factors on mortality and antimicrobial drug use. The results of this study show that a system where small farms raise the calves from their own herds has a substantial potential to improve animal health and reduce antimicrobial drug use. PMID- 26879058 TI - Bayesian evaluation of clinical diagnostic test characteristics of visual observations and remote monitoring to diagnose bovine respiratory disease in beef calves. AB - Accurate diagnosis of bovine respiratory disease (BRD) in beef cattle is a critical facet of therapeutic programs through promotion of prompt treatment of diseased calves in concert with judicious use of antimicrobials. Despite the known inaccuracies, visual observation (VO) of clinical signs is the conventional diagnostic modality for BRD diagnosis. Objective methods of remotely monitoring cattle wellness could improve diagnostic accuracy; however, little information exists describing the accuracy of this method compared to traditional techniques. The objective of this research is to employ Bayesian methodology to elicit diagnostic characteristics of conventional VO compared to remote early disease identification (REDI) to diagnose BRD. Data from previous literature on the accuracy of VO were combined with trial data consisting of direct comparison between VO and REDI for BRD in two populations. No true gold standard diagnostic test exists for BRD; therefore, estimates of diagnostic characteristics of each test were generated using Bayesian latent class analysis. Results indicate a 90.0% probability that the sensitivity of REDI (median 81.3%; 95% probability interval [PI]: 55.5, 95.8) was higher than VO sensitivity (64.5%; PI: 57.9, 70.8). The specificity of REDI (median 92.9%; PI: 88.2, 96.9) was also higher compared to VO (median 69.1%; PI: 66.3, 71.8). The differences in sensitivity and specificity resulted in REDI exhibiting higher positive and negative predictive values in both high (41.3%) and low (2.6%) prevalence situations. This research illustrates the potential of remote cattle monitoring to augment conventional methods of BRD diagnosis resulting in more accurate identification of diseased cattle. PMID- 26879059 TI - [Genomic Tests as Predictors of Breast Cancer Patients Prognosis]. AB - Hormonal dependent breast cancer is a heterogeneous disease from a molecular and clinical perspective. The relapse risk of early breast cancer patients treated with adjuvant hormonal therapy varies. Validated predictive markers concerning adjuvant cytotoxic treatment are still lacking in ER+/ HER2- breast cancer, which has a good prognosis in general. This can lead to the inefficient chemotherapy indication. Molecular classification of breast cancer reports evidence about the heterogeneity of hormonal dependent breast cancer and its stratification to different groups with different characteristics. Multigene assays work on the molecular level, and their aim is to provide patients risk stratification and therapy efficacy prediction. The position of multigene assays in clinical practice is not stabile yet. Non uniform level of evidence connected to patients prognosis interpretations and difficult comparison of tests are the key problems, which prevent their wide clinical use. The article is a summary of some of the most important multigene assays in breast cancer and their current position in oncology practice. PMID- 26879060 TI - [Potential of Long Non- coding RNA Molecules in Diagnosis of Tumors]. AB - Long non-coding RNA molecules (lncRNA) are defined as molecules over 200 nucleotides long that are localized in the nucleus and cytoplasm of cells. Although function of most lnRNA is not known, it is obvious that they are involved in various biological processes. LncRNA play a key role in transcriptional as well as posttranscriptional regulatory pathways and are involved in important cell processes, such as proliferation, differentiation, apoptosis but also pathogenesis of various diseases. Their dysregulation is important in steps of tumor transformation. In this review, we will describe the nature, function and molecular basis of these molecules as well as their diagnostic potential. The main focus of this review is the usage of these molecules in the most often diagnosed tumors in the Czech population--colorectal carcinoma, breast and prostate carcinomas. PMID- 26879061 TI - The Role of Heat Shock Proteins in Leukemia. AB - Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are molecular chaperones; their expression is increased after exposure of cells to conditions of environmental stress, including heat shock, heavy metals, oxidative stress, or pathologic conditions, such as ischemia, infection, and inflammation. Their protective function is to help the cell cope with lethal conditions. The HSPs are a class of proteins which, in normal cells, are responsible for maintaining homeostasis, interacting with diverse protein substrates to assist in their folding, and preventing the appearance of folding intermediates that lead to misfolded or damaged molecules. They have been shown to interact with different key apoptotic proteins and play a crucial role in regulating apoptosis. Several HSPs have been demonstrated to directly interact with various components of tightly regulated caspase-dependent programmed cell death. These proteins also affect caspase independent apoptosis by interacting with apoptogenic factors. Heat shock proteins are aberrantly expressed in hematological malignancies. Because of their prognostic implications and functional role in leukemias, HSPs represent an interesting target for antileukemic therapy. This review will describe different molecules interacting with anti-apoptotic proteins HSP70 and HSP90, which can be used in cancer therapy based on their inhibition. PMID- 26879062 TI - [Survival Analysis Three-year Follow-up of Pacients with Head and Neck Cancer]. AB - BACKGROUND: Patients with head and neck cancer are predominantnly at the risk for malnutrition. Monitoring of nutritional status and pre-treatment variables can favorably observe many prognostic indicators for overall survival in head and neck cancer before and during oncological treatment up to three years in head and neck cancer pacients. MATERIALS AND METHODS: In 726 patients diagnosed head and neck cancer patients with curative intent, were collected data according to the monitoring scheme of observation. As a clinical important of uninteded weight loss was defined weight loss 10% in input (T0). Differences in groups were analysed by Coxs regression with adjustments for important demografic and tumor related data. RESULTS: The acceptance of the percutaneous endoscopic gastrostomy was a key factor for less complications and to improve tolerance of anticancer treatment. Men-smokers have the highest risk of cardiovascular mortality. Men stop-smokers have the most significant life extension of 11 to 22 months; p < 0.007. Men-non-smokers have a life extension of 15 to 23 months (p < 0.005) and having its lowest cardiovascular mortality (11%). Women tolerate cancer better, have minor subjective complaints and a lower number of complications but significantly higher consumption of antidepressants (p < 0.003). While men have higher analgesic consumption (p < 0.001). Weight loss > 10% significantly correlates with the clinical manifestations of malnutrition and is associated with an increase in complications and mortality dependent cancer (p < 0.008). CONCLUSION: Consistent assessment of nutritional status with early intervention is considered as an essential part of comprehensive anticancer treatment. An independent risk factor for cancer-dependent mortality is considered weight loss of > 5% with a BMI < 21 at time T0 or weight loss > 10% weight T0 in BMI 21- 29 and continuing weight loss to T12 and also BMI 30. The highest-risk profile has a male sex-smoker, age > 63, hypopharyngeal carcinoma, stage III- IV, weight loss of > 10% and non-acceptance of percutaneous endoscopic gastrostomy. Another long term observation of monitored nutritional status with intervention, clinical status and quality of life are needed. PMID- 26879063 TI - Predicting Vitality Change in Older Breast Cancer Survivors after Primary Treatment--an Approach Based on Using Time-related Difference of Pro-inflammatory Marker C-reactive Protein. AB - BACKROUND: We aimed to determine prognosis of vitality change and functional status of breast cancer survivors after primary oncological treatment using time related differences of elevated levels of highly sensitive proinflammatory C reactive protein (CRP). PATIENTS AND METHODS: The test group consisted of 46 elderly breast cancer survivors (median age was 65 years) who completed Vitality Scale of Short Form 36 (SF-36) after completing treatment and another retrospectively at diagnosis. Data on tumor-related factors, treatment, and outcomes were obtained retrospectively from medical records, and linear regression analysis was performed. CRP was followed at diagnosis and one year after primary treatment. Within the scope of this study, clinically important difference in the Vitality Scale was set at five points of change. RESULTS: Results showed a statistically significant relationship between CRP change and vitality component of SF-36 change (rs = - 0.350, p = 0.023) in which a decrease in CRP inversely correlated with the quality of life component. The overall change was 1.078 of the vitality scale score (approximately 1 point) for each 1 unit decrease of CRP (1 mg/ L). Association of CRP levels (before and after treatment, its difference between these time points) with age, number of comorbidities and stage of the disease was analyzed and no statistically significant relationship was found in our study. CONCLUSION: Preliminary results suggested time-related differences in elevated CRP levels as a potentially suitable predictor for change in vitality status for long term, chronic condition for older breast cancer survivors. We suggest the interpretation schema including an understanding that CRP change of 5 mg/ L and more should be considered a potential risk factor for subsequent negative clinical outcomes. PMID- 26879064 TI - Successful Associating Liver Partition and Portal Vein Ligation after Unsuccessful Double TACE Procedure Complicated with Sepsis and Pancreatitis. AB - The associating liver partition and portal vein ligation (ALPPS) is a novel procedure with increasing number of scientific and clinical studies, and by now, it showed to be efficient and safe procedure in selected group of patients. Here we present the first case of ALPPS done after double TACE procedure in a 64-years old female patient with extensive hepatocellular carcinoma of the right liver lobe. The procedure was successful and liver remnant showed significant 90% hypertrophy which proves that ALPPS sometimes can be performed after palliative procedures in liver malignancies. PMID- 26879065 TI - [Successful Therapy of Czech Patients with ROS1 Translocation by Crizotinib]. AB - Targeted therapy of lung cancer has brought significant improvement in prognosis for a lot of patients with EGFR-sensitive mutations and ALK translocations. Other clinical studies have shown ROS1 translocation as another potential target. Our case report brings probably the first successful use of crizotininib in a patient with ROS1 translocation in the Czech Republic. Treatment was well-tolerated and persists continually. During the control PET/ CT scans, partial regression of the disease was observed. ROS1 translocation becomes another promising target for our patients. Therefore, in our opinion, serious discussion about its inclusion among the basic genetic testing in lung adenocarcinomas should occur. PMID- 26879066 TI - B-IGEV (bortezomib plus IGEV) versus IGEV before high-dose chemotherapy followed by autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: a randomized, phase II trial of the Fondazione Italiana Linfomi (FIL). AB - This randomized, multicenter study evaluates the addition of bortezomib (13 mg/m(2)) to IGEV (B-IGEV) in patients with relapsed/refractory Hodgkin Lymphoma (HL). Patients received either four courses of IGEV alone (n = 40) or B-IGEV (n = 40). The primary endpoint was the complete response (CR) proportion, evaluated by FDG-PET, after induction chemotherapy. CR proportion was 39% with B-IGEV and 53% with IGEV. PFS and OS were similar between the two groups (two-year PFS: 58% vs 56%; two-year OS: 93% vs 81%). The PET-negative status after treatment was the only variable favorably influencing both PFS (two-year PFS: 77% vs 40%; p = 0.002) and OS (two-year OS: 100% vs 76%; p < 0.001). Toxicity was overall similar with the two regimens. The addition of bortezomib to IGEV does not improve response in relapsed/refractory HL patients. However, its favorable therapeutic and safety profile, and the prognostic role of pre-transplant PET negativity in patients receiving IGEV-based regimens are confirmed. PMID- 26879068 TI - Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy. AB - Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (beta = 0.005, p = 0.989); baseline RVEF (beta = 0.270, p = 0.493); baseline RVFAC (beta = -0.367, p = 0.06); baseline basal strain (beta = -0.342, p = 0.462) after a mean follow up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF. PMID- 26879067 TI - Validation of self-reported figural drawing scales against anthropometric measurements in adults. AB - OBJECTIVE: The aim of the present study was to validate figural drawing scales depicting extremely lean to extremely obese subjects to obtain proxies for BMI and waist circumference in postal surveys. DESIGN: Reported figural scales and anthropometric data from a large population-based postal survey were validated with measured anthropometric data from the same individuals by means of receiver operating characteristic curves and a BMI prediction model. SETTING: Adult participants in a Scandinavian cohort study first recruited in 1990 and followed up twice since. SUBJECTS: Individuals aged 38-66 years with complete data for BMI (n 1580) and waist circumference (n 1017). RESULTS: Median BMI and waist circumference increased exponentially with increasing figural scales. Receiver operating characteristic curve analyses showed a high predictive ability to identify individuals with BMI > 25.0 kg/m2 in both sexes. The optimal figural scales for identifying overweight or obese individuals with a correct detection rate were 4 and 5 in women, and 5 and 6 in men, respectively. The prediction model explained 74 % of the variance among women and 62 % among men. Predicted BMI differed only marginally from objectively measured BMI. CONCLUSIONS: Figural drawing scales explained a large part of the anthropometric variance in this population and showed a high predictive ability for identifying overweight/obese subjects. These figural scales can be used with confidence as proxies of BMI and waist circumference in settings where objective measures are not feasible. PMID- 26879069 TI - Comparison of the Effect of Rosuvastatin 2.5 mg vs 20 mg on Coronary Plaque Determined by Angioscopy and Intravascular Ultrasound in Japanese With Stable Angina Pectoris (from the Aggressive Lipid-Lowering Treatment Approach Using Intensive Rosuvastatin for Vulnerable Coronary Artery Plaque [ALTAIR] Randomized Trial). AB - Diminishing yellow color, evaluated by coronary angioscopy, is associated with plaque stabilization and regression. Our aim was to assess the effect of aggressive lipid-lowering therapy with rosuvastatin on plaque regression and instability. Thirty-seven patients with stable angina or silent myocardial ischemia who planned to undergo elective percutaneous coronary intervention and had angioscopic yellow plaques of grade 2 or more were randomized to high-dose (group H, 20 mg/day, n = 18) or low-dose (group L, 2.5 mg/day, n = 19) rosuvastatin therapy for 48 weeks. Yellow plaque was graded on a 4-point scale of 0 (white) to 3 (bright yellow) by angioscopy, and plaque volume was determined by intravascular ultrasound for plaques with a length of 5 to 15 mm. Color and volume were assessed at baseline and after 48 weeks by the investigators blinded to the rosuvastatin dosage, and were compared between the 2 dosing groups. The level of low-density lipoprotein-cholesterol decreased from 130.3 +/- 25.5 mg/dl to 61.7 +/- 16.5 mg/dl (-50 +/- 19%: high intensity) in group H (p <0.001) and from 130.9 +/- 28.5 mg/dl to 89.7 +/- 29.0 mg/dl (-30 +/- 22%: moderate intensity) in group L (mean +/- SD, p <0.001). The average color grade of yellow plaques decreased from 2.0 to 1.5 in group H (p <0.001) and from 2.0 to 1.6 in group L (p <0.001) after 48 weeks. Plaque volume decreased significantly in group H but not in group L. The percent change in plaque volume was significantly larger in group H than in group L (p = 0.005). In conclusion, both high-dose and low-dose rosuvastatin increased plaque stability. However, high-dose rosuvastatin was more effective than low-dose rosuvastatin in inducing plaque volume regression. Clinical Trial Registration No: UMIN-CTR, UMIN000003276. PMID- 26879070 TI - Appropriate Use of Antithrombotic Medication in Canadian Patients With Nonvalvular Atrial Fibrillation. AB - This national chart audit of 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices sought to examine the management of Canadian patients with AF through an evidence-based, guideline-recommended approach. The appropriate use of oral anticoagulants (OACs) in this patient population and the potential factors guiding OAC choice were examined. Suboptimal dosing was seen. In patients on warfarin, 30.9% had not achieved a time in therapeutic range (TTR) in excess of 65% and, despite current Canadian guideline recommendations, were continued on warfarin rather than one of the novel OACs. In patients who received no antithrombotic therapy, 65.5% met criteria for treatment with an OAC. In addition, 62.8% of patients who were treated with acetylsalicylic acid monotherapy met guideline criteria for the use of an OAC. In those patients treated with an OAC, 24.8% were not on the recommended dose based on the product monograph or, if on warfarin, had a TTR <65%. Of the patients on novel OACs (NOACs), 7.4% of patients were underdosed, whereas overdosing was seen in 4.3%. Factors that may have contributed to dosing outside recommendations included underestimation of stroke risk, overestimation of bleed risk, compliance concerns, and lack of provincial reimbursement. In conclusion, significant correctable gaps remain in optimal treatment for stroke prevention in AF. PMID- 26879071 TI - Dual-doping to suppress cracking in spinel LiMn2O4: a joint theoretical and experimental study. AB - Electrochemical cycling stabilities were compared for undoped and Al/Co dual doped spinel LiMn2O4 synthesized by solid state reactions. We observed the suppression of particle fracture in Al/Co dual-doped LiMn2O4 during charge/discharge cycling and its distinguishable particle morphology with respect to the undoped material. Systematic first-principles calculations were performed on undoped, Al or Co single-doped, and Al/Co dual-doped LiMn2O4 to investigate their structural differences at the atomistic level. We reveal that while Jahn Teller distortion associated with the Mn(3+)O6 octahedron is the origin of the lattice strain, the networking -i.e. the distribution of mixed valence Mn ions - is much more important to release the lattice strain, and thus to alleviating particle cracking. The calculations showed that the lattice mismatching between Li(+) intercalation and deintercalation of LiMn2O4 can be significantly reduced by dual-doping, and therefore also the volumetric shrinkage during delithiation. This may account for the near disappearance of cracks on the surface of Al/Co LiMn2O4 after 350 cycles, while some obvious cracks have developed in undoped LiMn2O4 at similar particle size even after 50 cycles. Correspondingly, Al/Co dual-doped LiMn2O4 showed a good cycling stability with a capacity retention of 84.1% after 350 cycles at a rate of 1C, 8% higher than the undoped phase. PMID- 26879072 TI - Characteristics of gastric stump cancer: A single hospital retrospective analysis of 262 patients. AB - BACKGROUND: Owing to its relative rarity, the characteristics of gastric stump cancer (GSC) have not been fully understood. In this study, we clarified the detailed characteristics from a large cohort of GSC patients. PATIENTS AND METHODS: For this retrospective cohort study from 1 hospital in Japan, we recruited 262 GSC patients who underwent surgery for GSC between 1984 and 2012. GSC was defined in accordance with Japanese Gastric Cancer Association. Stage was categorized in accordance with the 7th TNM classification for primary gastric cancer. RESULTS: Although the time interval between the primary and second operations differed significantly depending on the primary disease (34.3 years for benign vs 9.9 years for malignant on average), it did not influence survival. The 5-year overall survival rates of patients with N0, N1, N2, and N3 were 70.4%, 27.7%, 21.8%, and 6.4%, respectively, whereas the rates for those with stage I, II, III, and IV were 77.8%, 37.4%, 18.6%, and 10.5%, respectively. Recurrence in the peritoneum was the most common pattern, followed by recurrence in the local region or lymph nodes. The Cox proportional hazard model demonstrated that age > 65, T stage, N stage, and tumor histology were significant independent prognostic factors for survival, whereas neither primary disease nor primary anastomosis type significantly impacted survival. CONCLUSION: Neither primary disease nor anastomosis type affected survival significantly, despite significant differences in their characteristics. In addition, the time interval between the primary and second surgery did not impact survival. PMID- 26879073 TI - Establishment of a rat model: Associating liver partition with portal vein ligation for staged hepatectomy. AB - BACKGROUND: We adapted the anatomically oriented parenchyma-preserving resection technique for associating liver partition with portal vein ligation (PVL) for staged hepatectomy (ALPPS) in rats and examined the role of revascularization in intrahepatic size regulation. METHODS: We performed the procedures based on anatomic study. The ALPPS procedure consisted of a 70% PVL (occluding the left median, left lateral, and right lobes), parenchymal transection (median lobe) and partial (10%) hepatectomy (PHx; caudate lobe). The transection effect was evaluated by measuring the extent of hepatic atrophy or regeneration of individual liver lobes in the ALPPS and control groups (70% PVL and 10% PHx without transection). The survival rates after stage II resection and collateral formation within the portal vein system was examined. RESULTS: Anatomic study revealed a close spatial relationship between the demarcation line and the middle median hepatic vein. This enabled placing the transection plane without injuring the hepatic vein. Transection was achieved via stepwise clamping, followed by 2-3 parenchyma-preserving piercing sutures on both sides of the clamp. Ligated liver lobes atrophy was significantly enhanced after ALPPS compared with the control group. In contrast, both a significantly greater relative weight of the regenerated lobe and proliferation index on the first postoperative day were observed. All animals tolerated stage II-resection without complications. Portoportal collaterals were only observed in the control group. CONCLUSION: We developed an anatomically precise technique for parenchymal transection. The lack of a dense vascular network between the portalized and deportalized lobes may play an important role in accelerating regeneration and atrophy augmentation. PMID- 26879074 TI - Relationship of the Cricothyroid Space with Vocal Range in Female Singers. AB - OBJECTIVES: This study aims to investigate the relationship between the anterior cricothyroid (CT) space at rest with vocal range in female singers. Potential associations with and between voice categories, age, ethnicity, anthropometric indices, neck dimensions, laryngeal dimensions, vocal data along with habitual speaking fundamental frequency were also explored. STUDY DESIGN: This is a cohort study. METHODS: Laryngeal dimensions anterior CT space and heights of the thyroid and cricoid cartilages were measured using ultrasound in 43 healthy, classically trained, female singers during quiet respiration. Voice categories (soprano and mezzo-soprano), age, ethnicity, weight, height, body mass index, neck circumference and length, anterior thyroid and cricoid cartilage heights, practice and performance vocal range, lowest and highest practice and performance notes along with habitual speaking fundamental frequency were collected. RESULTS: The main finding was that mezzo-sopranos have a significantly wider resting CT space than sopranos (11.6 mm versus 10.4 mm; P = 0.007). Mezzo-sopranos also had significantly lower "lowest and highest" performance notes than sopranos. There was no significant correlation between the magnitudes of the anterior CT space with vocal range. The participants with the narrowest and widest anterior CT space had similar vocal ranges. CONCLUSIONS: These results suggest that the CT space is not the major determinant of performance vocal range. PMID- 26879075 TI - Phasegram Analysis of Vocal Fold Vibration Documented With Laryngeal High-speed Video Endoscopy. AB - INTRODUCTION: In a recent publication, the phasegram, a bifurcation diagram over time, has been introduced as an intuitive visualization tool for assessing the vibratory states of oscillating systems. Here, this nonlinear dynamics approach is augmented with quantitative analysis parameters, and it is applied to clinical laryngeal high-speed video (HSV) endoscopic recordings of healthy and pathological phonations. METHODS: HSV data from a total of 73 females diagnosed as healthy (n = 42), or with functional dysphonia (n = 15) or with unilateral vocal fold paralysis (n = 16), were quantitatively analyzed. Glottal area waveforms (GAW) and left and right hemi-GAWs (hGAW) were extracted from the HSV recordings. Based on Poincare sections through phase space-embedded signals, two novel quantitative parameters were computed: the phasegram entropy (PE) and the phasegram complexity estimate (PCE), inspired by signal entropy and correlation dimension computation, respectively. RESULTS: Both PE and PCE assumed higher average values (suggesting more irregular vibrations) for the pathological as compared with the healthy participants, thus significantly discriminating healthy group from the paralysis group (P = 0.02 for both PE and PCE). Comparisons of individual PE or PCE data for the left and the right hGAW within each subject resulted in asymmetry measures for the regularity of vocal fold vibration. The PCE-based asymmetry measure revealed significant differences between the healthy group and the paralysis group (P = 0.03). CONCLUSIONS: Quantitative phasegram analysis of GAW and hGAW data is a promising tool for the automated processing of HSV data in research and in clinical practice. PMID- 26879076 TI - Psychiatric risk factors predicting post-liver transplant physical and psychiatric complications: a literature review. AB - OBJECTIVES: The psychiatric assessment of potential liver transplant recipients is becoming increasingly common in clinical practice. In such assessments, the psychiatrist is invited by the transplant team to assess the patient prior to the patient receiving a transplant liver to identify factors that could predict an unsuccessful post-transplant course, whether this is from a psychiatric or physical perspective. This review examined published research from 2000 to 2014 on psychological risk factors predicting post-transplant physical and psychiatric complications. CONCLUSIONS: Based on the strength of the evidence available, our review identified four risk factors: mood disorders; social supports; substance misuse; and alcohol dependence. These factors could potentially provide a framework to guide the evaluation and prediction of psychological and physical complications post-liver transplantation. PMID- 26879077 TI - Adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts entering puberty: a 3-year follow-up study. AB - PURPOSE: To investigate changes in bone mineral density (BMD) in rhythmic gymnasts (RG) entering puberty and their age-matched untrained controls (UC) over the 36-month period, and associations with leptin, adiponectin and ghrelin over this period. METHODS: Whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD, WB bone mineral content (BMC), and leptin, adiponectin and ghrelin were measured in 35 RG and 33 UC girls at baseline and at 12-month intervals over the next 3 years. The change over the 36 months was calculated (? score). RESULTS: The pubertal development over the next 36 months was slower in RG compard to UC, while there was no difference in bone age development between the groups. BMD at all sites was higher in RG in comparison with UC at every measurement point. ?LS BMD and ?FN BMD, but not ?WB BMD and ?WB BMC, were higher in RG compared with UC. None of the measured hormones at baseline or their ? scores correlated with ?BMD and ?BMC in RG. Baseline fat free mass correlated with ?WB BMD and ?WB BMC in RG, while baseline leptin was related to ?WB BMC, ?WB BMD and ?LS BMD in UC. CONCLUSIONS: Measured baseline hormones and their ? scores did not correlate with increases in bone mineral values in RG entering puberty. Although the pubertal development in RG was slower than in UC, high-intensity training appeared to increase BMD growth and counterbalance negative effects of slow pubertal develpment, lower fat mass and leptin in RG. PMID- 26879078 TI - Troponin in Cardiovascular Disease Prevention: Updates and Future Direction. AB - Cardiac troponin has been well described as the preferred biomarker for diagnosis of myocardial infarction due to the high sensitivity and specificity for myocardial injury. Numerous other conditions apart from acute coronary syndrome can also lead to small elevations in troponin levels. However, the use of cTn as prognostic biomarker for the primary assessment of cardiovascular risk in asymptomatic patient has only recently been described. And with the development of newer generations of high-sensitivity cardiac troponin assays that can detect 10-fold lower concentrations of troponin, the potential value cTn in the prevention and management of asymptomatic cardiovascular disease has come to the fore. This review provides an overview of the transition of cardiac troponin as a marker of acute myocardial injury to one that detects sub-clinical injury. Evidence continues to show that high-sensitivity troponin is emerging as one of the most powerful prognostic biomarkers for the assessment of cardiovascular risk in the general population. PMID- 26879080 TI - An American physician's foray into Scandinavian healthcare. AB - The article describes the experience of the author, an American Physician, seeking care for an uncommon orthopedic condition. Unable to find adequate treatment in the United States, the author traveled to Finland for surgical treatment. PMID- 26879079 TI - An Update on the Utility of Coronary Artery Calcium Scoring for Coronary Heart Disease and Cardiovascular Disease Risk Prediction. AB - Estimating cardiovascular disease (CVD) risk is necessary for determining the potential net benefit of primary prevention pharmacotherapy. Risk estimation relying exclusively on traditional CVD risk factors may misclassify risk, resulting in both undertreatment and overtreatment. Coronary artery calcium (CAC) scoring personalizes risk prediction through direct visualization of calcified coronary atherosclerotic plaques and provides improved accuracy for coronary heart disease (CHD) or CVD risk estimation. In this review, we discuss the most recent studies on CAC, which unlike historical studies, focus sharply on clinical application. We describe the MESA CHD risk calculator, a recently developed CAC based 10-year CHD risk estimator, which can help guide preventive therapy allocation by better identifying both high- and low-risk individuals. In closing, we discuss calcium density, regional distribution of CAC, and extra-coronary calcification, which represent the future of CAC and CVD risk assessment research and may lead to further improvements in risk prediction. PMID- 26879081 TI - Surgical outcome of mesh and suture repair in primary umbilical hernia: postoperative complications and recurrence. AB - PURPOSE: To compare recurrence and surgical complications following two dominating techniques: the use of suture and mesh in umbilical hernia repair. METHODS: 379 consecutive umbilical hernia repair procedures performed between 1 January 2005 and 14 March 2014 in a university setting were included. Gathering was made using International Classification of Diseases codes for both procedure and diagnosis. Each patient record was scrutinized with respect to 45 variables, and the results entered in a database. RESULTS: Exclusion <18 years-of-age (32), non-primary umbilical hernia (25), wrong diagnosis (7), concomitant major abdominal surgery (5), double registration (3) and pregnancy (1) left 306 patients eligible for analysis. Gender distribution was 97 women and 209 men. There was no difference between mesh and suture with regard to the primary outcome variable, cumulative recurrence rate, 8.4 %. Recurrence was both self reported and found on clinical revisit and defined as recurrence when verified by a clinician and/or radiologist. Results presented as odds ratio (OR) with 95 % confidence interval (CI) show a significantly higher risk for recurrence in patients with a coexisting hernia OR 2.84, 95 % CI 1.24-6.48. Secondary outcome, postoperative surgical complication (n = 51 occurrences), included an array of postoperative surgical events commencing within 30 days after surgery. Complication rate was significantly higher in patients receiving mesh repair OR 6.63, 95 % CI 2.29-20.38. CONCLUSIONS: Suture repair decreases the risk for surgical complications, especially infection without an increase in recurrence rate. The risk for recurrence is increased in patients with a history of another hernia. PMID- 26879082 TI - Improving cellulase production by Aspergillus niger using adaptive evolution. AB - OBJECTIVES: To evaluate the potential of adaptive evolution as a tool in generating strains with an improved production of plant biomass degrading enzymes. RESULTS: An Aspergillus niger cellulase mutant was obtained by adaptive evolution. Physiological properties of this mutant revealed a five times higher cellulose production than the parental strain. Transcriptomic analysis revealed that the expression of noxR, encoding the regulatory subunit of the NADPH oxidase complex, was reduced in the mutant compared to the parental strain. Subsequent analysis of a noxR knockout strain showed the same phenotypic effect as observed for the evolution mutant, confirming the role of NoxR in cellulose degradation. CONCLUSIONS: Adaptive evolution is an efficient approach to modify a strain and activate genes involved in polysaccharide degradation. PMID- 26879083 TI - Surgical management of the biconcave (B2) glenoid. AB - Glenohumeral osteoarthritis produces a wide spectrum of glenoid pathology. The B2 glenoid is defined by asymmetric posterior bone loss with the development of a biconcavity and posterior translation of the humeral head. Progressive bone loss results in increasing glenoid retroversion, which must be corrected during anatomic shoulder arthroplasty. The goals of arthroplasty should also include centering the humeral head and restoring the normal glenoid joint line. When there is minimal bone loss, this may be accomplished with a standard glenoid component and asymmetric reaming. More significant bone loss requires bone grafting or the use of an augmented glenoid component. Reverse shoulder arthroplasty is also an option for older patients or patients with severe bone loss. PMID- 26879085 TI - Urogynecology digest : Presented by Momoe Hyakutake. PMID- 26879084 TI - Small increases in enhancement on MRI may predict survival post radiotherapy in patients with glioblastoma. AB - To assess impact of volumetric changes in tumour volume post chemoradiotherapy in glioblastoma. Patients managed with chemoradiotherapy between 2008 and 2011 were included. Patients with incomplete MRI sets were excluded. Analyses were performed on post-operative MRI, and MRIs at 1 month (M+1), 3 months (M+3), 5 months (M+5), 7 months (M+7), and 12 months (M+12) post completion of RT. RANO definitions of response were used for all techniques. Modified RANO criteria and two volumetric analysis techniques were used. The two volumetric analysis techniques involved utility of the Eclipse treatment planning software to calculate the volume of delineated tissue: surgical cavity plus all surrounding enhancement (Volumetric) versus surrounding enhancement only (Rim). Retrospective analysis of 49 patients with median survival of 18.4 months. Using Volumetric analysis the difference in MS for patients who had a <5 % increase versus >=5 % at M+3 was 23.1 versus 15.1 months (p = 0.006), and M+5 was 26.3 versus 15.1 months (p = 0.006). For patients who were classified as progressive disease using modified RANO criteria at M+1 and M+3 there was a difference in MS compared with those who were not (M+1: 13.1 vs. 19.4 months, p = 0.017, M+3: 13.2 vs. 20.1 months, p = 0.096). An increase in the volume of cavity and enhancement of >=5 % at M+3 and M+5 post RT was associated with reduced survival, suggesting that increases in radiological abnormality of <25 % may predict survival. PMID- 26879086 TI - Urogynecology digest : Presented by Gregory Kanter. PMID- 26879088 TI - A simple method for panretinal imaging with the slit lamp. AB - Slit lamp biomicroscopy of the retina with a convex lens is a key procedure in clinical practice. The methods presented enable ophthalmologists to adequately image large and peripheral parts of the fundus using a video-slit lamp and freely available stitching software. A routine examination of the fundus with a slit lamp and a +90 D lens is recorded on a video film. Later, sufficiently sharp still images are identified on the video sequence. These still images are imported into a freely available image-processing program (Hugin, for stitching mosaics together digitally) and corresponding points are marked on adjacent still images with some overlap. Using the digital stitching program Hugin panoramic overviews of the retina can be built which can extend to the equator. This allows to image diseases involving the whole retina or its periphery by performing a structured fundus examination with a video-slit lamp. Similar images with a video slit lamp based on a fundus examination through a hand-held non-contact lens have not been demonstrated before. The methods presented enable those ophthalmologists without high-end imaging equipment to monitor pathological fundus findings. The suggested procedure might even be interesting for retinological departments if peripheral findings are to be documented which might be difficult with fundus cameras. PMID- 26879089 TI - Counterion-Controlled Self-Sorting in an Amphiphilic Calixarene Micellar System. AB - Molecular recognition of small molecules and ions by artificial receptors in microheterogeneous media such as micelles and vesicles can, in principle, provide better models of biological systems in comparison with bulk solutions. In this work we have investigated the complexation of an organic fluorescent probe with amphiphilic calixarene receptor below and above the critical micelle concentration (CMC). For concentrations below the CMC, the probe forms a host guest complex with the calixarene behaving like a traditional host-guest system operating in bulk solution. Above the CMC, multiple equilibrium processes are established and the probe can exchange between the recognition site of the calixarene in the monomeric state, micellized state and/or the micellar hydrophobic core. Careful analysis of the results obtained from NMR spectroscopy and fluorescence experiments allowed us to propose a quantitative model to describe the system. The increment of the local concentration of Na(+) counterions at the Stern layer displace the dye to the micelle core through competitive binding of Na(+) in the cavity of the receptor and is decisive for the observed self-sorting behavior. PMID- 26879087 TI - Experts' recommendations for the management of cardiogenic shock in children. AB - Cardiogenic shock which corresponds to an acute state of circulatory failure due to impairment of myocardial contractility is a very rare disease in children, even more than in adults. To date, no international recommendations regarding its management in critically ill children are available. An experts' recommendations in adult population have recently been made (Levy et al. Ann Intensive Care 5(1):52, 2015; Levy et al. Ann Intensive Care 5(1):26, 2015). We present herein recommendations for the management of cardiogenic shock in children, developed with the grading of recommendations' assessment, development, and evaluation system by an expert group of the Groupe Francophone de Reanimation et Urgences Pediatriques (French Group for Pediatric Intensive Care and Emergencies). The recommendations cover four major fields of application such as: recognition of early signs of shock and the patient pathway, management principles and therapeutic goals, monitoring hemodynamic and biological variables, and circulatory support (indications, techniques, organization, and transfer criteria). Major principle care for children with cardiogenic shock is primarily based on clinical and echocardiographic assessment. There are few drugs reported as effective in childhood in the medical literature. The use of circulatory support should be facilitated in terms of organization and reflected in the centers that support these children. Children with cardiogenic shock are vulnerable and should be followed regularly by intensivist cardiologists and pediatricians. The experts emphasize the multidisciplinary nature of management of children with cardiogenic shock and the importance of effective communication between emergency medical assistance teams (SAMU), mobile pediatric emergency units (SMUR), pediatric emergency departments, pediatric cardiology and cardiac surgery departments, and pediatric intensive care units. PMID- 26879090 TI - The individual level cost of pregnancy termination in Zambia: a comparison of safe and unsafe abortion. AB - Zambia has one of the most liberal abortion laws in sub-Saharan Africa. However, rates of unsafe abortion remain high with negative health and economic consequences. Little is known about the economic burden on women of abortion care seeking in low income countries. The majority of studies focus on direct costs (e.g. hospital fees). This article estimates the individual-level economic burden of safe and unsafe abortion care-seeking in Zambia, incorporating all indirect and direct costs. It uses data collected in 2013 from a tertiary hospital in Lusaka, (n = 112) with women who had an abortion. Three treatment routes are identified: (1) safe abortion at the hospital, (2) unsafe clandestine medical abortion initiated elsewhere with post-abortion care at the hospital and (3) unsafe abortion initiated elsewhere with post-abortion care at the hospital. Based on these three typologies, we use descriptive analysis and linear regression to estimate the costs for women of seeking safe and unsafe abortion and to establish whether the burden of abortion care-seeking costs is equally distributed across the sample. Around 39% of women had an unsafe abortion, incurring substantial economic costs before seeking post-abortion care. Adolescents and poorer women are more likely to use unsafe abortion. Unsafe abortion requiring post-abortion care costs women 27% more than a safe abortion. When accounting for uncertainty this figure increases dramatically. For safe and unsafe abortions, unofficial provider payments represent a major cost to women.This study demonstrates that despite a liberal legislation, Zambia still needs better dissemination of the law to women and providers and resources to ensure abortion service access. The policy implications of this study include: the role of pharmacists and mid-level providers in the provision of medical abortion services; increased access to contraception, especially for adolescents; and elimination of demands for unofficial provider payments. PMID- 26879091 TI - Levels and variations in the quality of facility-based antenatal care in Kenya: evidence from the 2010 service provision assessment. AB - Quality of care is emerging as an important concern for low- and middle-income countries working to expand and improve coverage. However, there is limited systematic, large-scale empirical guidance to inform policy design. Our study operationalized indicators for six dimensions of quality of care that are captured in currently available, standardized Service Provision Assessments. We implemented these measures to assess the levels and heterogeneity of antenatal care in Kenya. Using our indicator mix, we find that performance is low overall and that there is substantial variation across provinces, management authority and facility type. Overall, facilities performed highest in the dimensions of efficiency and acceptability/patient-centeredness, and lowest on effectiveness and accessibility. Public facilities generally performed worse or similarly to private or faith-based facilities. We illustrate how these data and methods can provide readily-available, low-cost decision support for policy. PMID- 26879092 TI - Parallel Atrophy of Cortex and Basal Forebrain Cholinergic System in Mild Cognitive Impairment. AB - The basal forebrain cholinergic system (BFCS) is the major source of acetylcholine for the cerebral cortex in humans. The aim was to analyze the pattern of BFCS and cortical atrophy in MCI patients to find evidence for a parallel atrophy along corticotopic organization of BFCS projections. BFCS volume and cortical thickness were analyzed using high-definition 3D structural magnetic resonance imaging data from 1.5-T and 3.0-T scanners of 64 MCI individuals and 62 cognitively healthy elderly controls from the European DTI study in dementia. BFCS volume reduction was correlated with thinning of cortical areas with known BFCS projections, such as Ch2 and parahippocampal gyrus in the MCI group, but not in the control group. Additionally, we found correlations between BFCS and cortex atrophy beyond the known corticotopic projections, such as between Ch4p and the cingulate gyrus. BFCS volume reduction was associated with regional thinning of cortical areas that included, but was not restricted to, the pattern of corticotopic projections of the BFCS as derived from animal studies. Our in vivo results may indicate the existence of more extended projections from the BFCS to the cerebral cortex in humans than that known from prior studies with animals. PMID- 26879094 TI - Idarubicin is a broad-spectrum enterovirus replication inhibitor that selectively targets the virus internal ribosomal entry site. AB - Enterovirus 71 (EV71) causes life-threatening diseases with neurological manifestations in young children. However, the treatment of EV71 infections remains an unmet medical need. Idarubicin (IDR) is an anthracycline compound that is used therapeutically for certain types of tumour. In this study, we identified IDR as an EV71 inhibitor, which displayed antiviral potency in the submicromolar range and substantially protected cells from the cytopathic effects and cell death caused by EV71 infections. The antiviral effects extended to several other enterovirus (EV) species, and these effects were independent of cytotoxicity or topoisomerase inhibition. Structure-activity relationship studies indicated the importance of the anthracycline scaffold for anti-EV potency. IDR effectively blocked the synthesis of viral protein and RNA, but not the viral proteolysis processes. Moreover, anthracyclines were demonstrated to suppress EV internal ribosomal entry site (IRES)-mediated translation; conversely, the cellular p53 IRES activity was not sensitive to IDR action. Inhibition of IRES-mediated translation by IDR correlated with the affinity of binding between IDR and the particular IRES. Moreover, IDR impaired binding between the EV71 IRES RNA and hnRNP A1, a known host IRES trans-acting factor. In sum, we have identified a USA FDA-approved anticancer drug with the new indication as a selective EV IRES binder and inhibitor. The finding may also provide leads for the development of novel antiviral therapies directed at the EV IRES RNA. PMID- 26879093 TI - Bidirectional Modulation of Numerical Magnitude. AB - Numerical cognition is critical for modern life; however, the precise neural mechanisms underpinning numerical magnitude allocation in humans remain obscure. Based upon previous reports demonstrating the close behavioral and neuro anatomical relationship between number allocation and spatial attention, we hypothesized that these systems would be subject to similar control mechanisms, namely dynamic interhemispheric competition. We employed a physiological paradigm, combining visual and vestibular stimulation, to induce interhemispheric conflict and subsequent unihemispheric inhibition, as confirmed by transcranial direct current stimulation (tDCS). This allowed us to demonstrate the first systematic bidirectional modulation of numerical magnitude toward either higher or lower numbers, independently of either eye movements or spatial attention mediated biases. We incorporated both our findings and those from the most widely accepted theoretical framework for numerical cognition to present a novel unifying computational model that describes how numerical magnitude allocation is subject to dynamic interhemispheric competition. That is, numerical allocation is continually updated in a contextual manner based upon relative magnitude, with the right hemisphere responsible for smaller magnitudes and the left hemisphere for larger magnitudes. PMID- 26879095 TI - Transcranial Direct Current Stimulation in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD): A Pilot Study. AB - Studies investigating the possible benefits of transcranial direct current stimulation on left dorsolateral prefrontal cortex in children and adolescents with attention-deficit hyperactivity disorder (ADHD) have not been performed. This study assesses the effect of transcranial direct current stimulation in children and adolescents with ADHD on neuropsychological tests of visual attention, visual and verbal working memory, and inhibitory control. An auto matched clinical trial was performed involving transcranial direct current stimulation in children and adolescents with ADHD, using SNAP-IV and subtests Vocabulary and Cubes of the Wechsler Intelligence Scale for Children III (WISC III). Subjects were assessed before and after transcranial direct current stimulation sessions with the Digit Span subtest of the WISC-III, inhibitory control subtest of the NEPSY-II, Corsi cubes, and the Visual Attention Test (TAVIS-3). There were 9 individuals with ADHD according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. There was statistically significant difference in some aspects of TAVIS-3 tests and the inhibitory control subtest of NEPSY-II. Transcranial direct current stimulation can be related to a more efficient processing speed, improved detection of stimuli, and improved ability to switch between an ongoing activity and a new one. PMID- 26879096 TI - Factors impacting the success of post-mortem sperm rescue in the rhinoceros. AB - The goal of this study was to identify factors that influenced the ability to successfully rescue sperm post-mortem from rhinoceroses maintained in North American zoos. Factors considered included procedural technicalities, individual rhinoceros characteristics and timing. Gross testicular pathology was noted in 17.4% of males (4/23) but did not impact sperm recovery except in one case of azoospermia (4.3%). Of the males in which sperm recovery was attempted (n=21), 62% yielded quality samples considered adequate for cryopreservation (>= 30% motility with >= 2.0 forward progressive status). A high percentage of males (70.6%; 12/17) from which reproductive tissue was removed an d cooled <= 4 h after death yielded quality sperm samples, whereas only 25% (1/4) of males from which tissue was removed>4h after death yielded quality samples. Quality samples were recovered 1-51 h post-mortem from rhinoceroses 8 to 36 years old. Neither type of illness (prolonged or acute), or method of death (euthanasia or natural) affected the ability to harvest quality samples (P > 0.05). The Indian rhinoceros yielded significantly more sperm on average (40 * 10(9)) than the African black rhinoceros (3.6 * 10(9); P < 0.01) and the African white rhinoceros (3.2 * 10(9); P < 0.05). Across all species and samples assessed (n = 11), mean post-thaw sperm motility (41%), was only 15% less than pre-freeze motility (56%) and only decreased to 22% during the 6h post-thaw assessment period. Rhinoceros sperm rescue post-mortem is relatively successful across a wide range of variables, especially when tissues are removed and cooled promptly after death, and should be considered standard practice among zoos. PMID- 26879097 TI - Directional freezing of sperm and associated derived technologies. AB - Directional freezing has now completed 30 years of development since it was first introduced to cryobiology. In the field of sperm cryopreservation, directional freezing has been shown to be advantageous over slow freezing for numerous domestic and wildlife species. In particular, it was shown that freezing of large volume is possible. Furthermore, double freezing of sperm and freezing of sex sorted sperm are possible and became the routine in the sex sorted sperm industry. In wild animals, our labs and others showed that sperm from a wide range of terrestrial and aquatic species can be successfully cryopreserved using directional freezing. Finally, we will describe for the first time the successful freeze-drying of human sperm in an aseptic method. Using a device that produces clean liquid air, we froze human sperm in small droplets and then dried them in a bench top lyophilizer that was sterilized prior to use. More than 80% of DNA integrity was found after rehydration. PMID- 26879098 TI - Amplatzer Plug to Occlude the Internal Iliac Artery During Endovascular Aortic Aneurysm Repair: A Large Multicenter Study. AB - OBJECTIVE: During endovascular repair of abdominal aortic aneurysms (EVAR), in the absence of a distal iliac landing zone, the Amplatzer plug is increasingly being used to replace other internal iliac artery (IIA) embolization techniques. This study aimed at assessing the technical success, complication occurrence, and durability of the Amplatzer plug for IIA embolization. METHOD: From January 1, 2007 to December 31, 2013, all consecutive patients who underwent internal iliac embolization with an Amplatzer plug during EVAR were included in the study. There were 169 patients, (160 men, 9 women, mean 75 +/- 9 years), treated by unilateral (158 cases, 93%) or bilateral (11 cases, 7%) embolization of the IIA, performed either separately prior to (65 cases, 38.5%) or during EVAR (104 cases, 61.5%). Follow up CT scan and/or US scan were performed 1 month after treatment and yearly thereafter. The inclusions were done retrospectively but the series was continuous and consecutive. Data were collected and analyzed using acquisition REDCap software. RESULTS: The technical success rate was 97.6%. Failures were device migration (n = 1), navigation failure (n = 2), and release outside the target zone (n = 1). On average, 1.43 plugs were required to achieve the embolization. The average amount of contrast agent for the embolization procedure was 111 +/- 51 mL and the radiation dose was 127,777 +/- 89,528 mGy/cm(2). The total fluoroscopy time was 854 +/- 538 seconds. No re-canalization of the IIA trunk was observed during follow up. Complications were buttock claudication (n = 41, 24.3%), which resolved in 24 cases (58.5%, 24/41) at the first follow up, and intestinal ischemia requiring limited bowel resection in two cases. CONCLUSION: This multicenter study is the largest published to date. It demonstrates the efficacy and reliability of the Amplatzer plug to embolize the IIA during EVAR, with few side effects. PMID- 26879099 TI - Dosing Penalty of Erythropoiesis-Stimulating Agents After Switching From Originator to Biosimilar Preparations in Stable Hemodialysis Patients. PMID- 26879100 TI - A Study of the Amputee Experience of Viewing Self in the Mirror. AB - PURPOSE: To describe the trajectory of viewing self in a mirror after an ampu tation and participants' perceptions of what health care professionals should know about mirrors. DESIGN: Hermeneutic phenomenologyMETHODS: Focus groups were conducted to collect the research data. FINDINGS: The mirror experience had three key moments: decision, seeing, and consent. The trajectory of viewing self in a mirror had four key themes: mirror shock, mirror anguish, recognizing self, and acceptance: a new normal. Participants' recommendations for introducing the mirror after an amputation and using a mirror to avoid skin breakdown and infection, and correct gait and balance are described. CONCLUSIONS: This study provides a unique viewpoint into the world of those who have suffered amputation of a limb. CLINICAL RELEVANCE: Rehabilitation nurses and other health care professionals are encouraged through these participants to consider the effect and value of mirrors when caring for those who have had an amputation. PMID- 26879101 TI - Amygdala responses to quetiapine XR and citalopram treatment in major depression: the role of 5-HTTLPR-S/Lg polymorphisms. AB - OBJECTIVES: Genotype and drug pharmacology may contribute to variations in brain response to antidepressants. We examined the impact of two antidepressants with differential actions on serotonin transporter and the 5-HHTLPR-S/Lg polymorphisms on amygdala responses in major depressive disorder (MDD). METHODS: Caucasians with MDD were given either citalopram or quetiapine extended release for 8 weeks. Patients were genotyped for 5-HTTLPR. Clinical efficacy was assessed using the Hamilton Depression Rating Scale. fMRI responses to negative emotional faces were acquired at baseline, week 1 and week 8. The outcome measure was change in amygdala responses at week 8. RESULTS: Citalopram had no effect on amygdala responses in MDD patients with S/Lg alleles at weeks 1 and 8 compared with baseline, whereas it induced changes in amygdala responses in LL homozygotes. By contrast, quetiapine decreased amygdala responses at both time points in S/Lg carriers, and changes in amygdala responses at week 8 correlated with a reduction in depression scores. The small number of LL homozygotes in quetiapine group was a limitation. Efficacy of both treatments was comparable. CONCLUSIONS: These preliminary data suggest that pharmacological mechanisms and genetics need to be considered in the development of neuroimaging markers for the evaluation of antidepressant treatments. PMID- 26879102 TI - Trends in seasonal influenza vaccine uptake during pregnancy in Western Australia: Implications for midwives. AB - BACKGROUND: Antenatal influenza vaccination is an important public health intervention for preventing serious illness in mothers and newborns, yet uptake remains low. AIM: To evaluate trends in seasonal influenza vaccine coverage and identify determinants for vaccination among pregnant women in Western Australia. METHODS: We conducted an annual telephone survey in a random sample of post partum women who delivered a baby in Western Australia between 2012 and 2014. Women were asked whether influenza vaccination was recommended and/or received during their most recent pregnancy; women were also asked why or why they were not immunised. FINDINGS: Between 2012 and 2014, influenza vaccine coverage increased from 22.9% to 41.4%. Women who reported receiving the majority of their antenatal care from a private obstetrician were significantly more likely to have influenza vaccination recommended to them than those receiving the majority of their care from a public antenatal hospital or general practitioner (p<0.001). In 2014, the most common reason women reported for accepting influenza vaccination was to protect the baby (92.8%) and the most common reason for being unimmunised was lack of a healthcare provider recommendation (48.5%). DISCUSSION: Antenatal influenza vaccination uptake is increasing, but coverage remains below 50%. A recommendation from the principal care provider is an important predictor of maternal influenza vaccination. CONCLUSION: Antenatal care providers, including midwives, have a key role in providing appropriate information and evidence-based recommendations to pregnant women to ensure they are making informed decisions. Consistent recommendations from antenatal care providers are critical to improving influenza vaccine coverage in pregnant women. PMID- 26879104 TI - Distance Regulated Vesicle Fusion and Docking Mediated by beta-Peptide Nucleic Acid SNARE Protein Analogues. AB - Artificial SNARE analogues derived from SNARE proteins, which mediate synaptic membrane fusion, are of interest. They mimic the tetrameric alpha-helix bundle of the SNARE motif with various bio-oligomer recognition units. Interaction between complementary oligomers linked to the respective membrane by lipid or peptide anchors leads to proximity of vesicles and to fusion of lipid bilayers. beta Peptide nucleic acids were introduced as hybrid oligomers with the native SNARE protein transmembrane/linker sequence, in order to evaluate a fusion system that allows distance tuning of approaching membranes. Formation of a four-base pair beta-PNA double strand with 20 A length is sufficient for vesicle membrane fusion. Elongation of the recognition beta-PNA duplex in the linker region yielded a 40 A beta-peptide duplex and provided a vesicle-vesicle distance that only supported hemifusion of vesicle membranes. PMID- 26879103 TI - Labour induction for late-term or post-term pregnancy. AB - PROBLEM AND BACKGROUND: Approximately one in four women in Australia have their labour induced, and prolonged pregnancy is likely the most common reason for induction. Clinical guidelines recommend offering induction at 41 weeks, because it is thought that induction lowers the risk of stillbirth without increasing the Caesarean rate. However, the evidence behind this recommendation warrants closer investigation. QUESTIONS: What is the risk of stillbirth as women go past their due dates, and what are the benefits and risks of elective labour induction? FINDINGS: A large body of evidence shows that the relative risk of stillbirth increases starting after 37-38 weeks, but more recent data show the absolute risk does not rise substantially until 42 weeks, when it reaches 1 in 1000. As women get closer to 41 weeks, it is appropriate for midwives to discuss the benefits and risks of elective induction and expectant management. Meta-analyses that have studied the effects of elective induction were driven by the Hannah Post Term trial, which was limited by high rates of cross-over between groups. CONCLUSION: Ultimately, after receiving accurate, evidence-based information and guidance from health care providers, women have the right to decide whether they prefer to induce labour, or wait for spontaneous labour with appropriate foetal monitoring, as both are reasonable options. PMID- 26879106 TI - Human local and total heat losses in different temperature. AB - This study investigates the effects of operative temperature on the local and total heat losses, and the relationship between the heat loss and thermal sensation. 10 local parts of head, neck, chest, abdomen, upper arm, forearm, hand, thigh, leg and foot are selected. In all these parts, convection, radiation, evaporation, respiration, conduction and diffusion heat losses are analyzed when operative temperature is 23, 28, 33 and 37 degrees C. The local heat losses show that the radiation and convection heat losses are mainly affected by the area of local body, and the heat loss of the thigh is the most in the ten parts. The evaporation heat loss is mainly affected by the distribution of sweat gland, and the heat loss of the chest is the most. The total heat loss of the local body shows that in low temperature, the thigh, leg and chest have much heat loss, while in high temperature, the chest, abdomen, thigh and head have great heat loss, which are useful for clothing design. The heat losses of the whole body show that as the operative temperature increases, the radiation and convection heat losses decrease, the heat losses of conduction, respiration, and diffusion are almost constant, and the evaporation heat loss increases. By comparison, the heat loss ratios of the radiation, convection and sweat evaporation, are in agreement with the previous researches. At last, the formula about the heat loss ratio of convection and radiation is derived. It's useful for thermal comfort evaluation and HVAC (heating, ventilation and air conditioning) design. PMID- 26879105 TI - Double trouble: Portion size and energy density combine to increase preschool children's lunch intake. AB - BACKGROUND: Both portion size and energy density (ED) have substantial effects on intake; however, their combined effects on preschool children's intake have not been examined when multiple foods are varied at a meal. OBJECTIVE: We tested the effects on intake of varying the portion size and ED of lunches served to children in their usual eating environment. DESIGN: In a crossover design, lunch was served in 3 childcare centers once a week for 6weeks to 120 children aged 3 5y. Across the 6 meals, all items were served at 3 levels of portion size (100%, 150%, or 200%) and 2 levels of ED (100% or 142%). The lunch menu had either lower ED or higher-ED versions of chicken, macaroni and cheese, vegetables, applesauce, ketchup, and milk. Children's ratings of the foods indicated that the lower-ED and higher-ED meals were similarly well liked. RESULTS: The total weight of food and milk consumed at meals was increased by serving larger portions (P<0.0001) but was unaffected by varying the ED (P=0.22). Meal energy intake, however, was independently affected by portion size and ED (both P<0.0001). Doubling the portions increased energy intake by 24% and increasing meal ED by 42% increased energy intake by 40%. These effects combined to increase intake by 175+/-12kcal or 79% at the higher-ED meal with the largest portions compared to the lower-ED meal with the smallest portions. The foods contributing the most to this increase were chicken, macaroni and cheese, and applesauce. The effects of meal portion size and ED on intake were not influenced by child age or body size, but were significantly affected by parental ratings of child eating behavior. CONCLUSION: Strategically moderating the portion size and ED of foods typically consumed by children could substantially reduce their energy intake without affecting acceptability. PMID- 26879108 TI - Individual and contextual correlates of obesity-related behaviours and obesity: the SPOTLIGHT project. PMID- 26879107 TI - Rescue of defective ATP8B1 trafficking by CFTR correctors as a therapeutic strategy for familial intrahepatic cholestasis. AB - BACKGROUND & AIMS: ATP8B1 deficiency is an autosomal recessive liver disease characterized by intrahepatic cholestasis. ATP8B1 mutation p.I661T, the most frequent mutation in European patients, results in protein misfolding and impaired targeting to the plasma membrane. Similarly, mutations in cystic fibrosis transmembrane conductance regulator (CFTR), associated with cystic fibrosis, impair protein folding and trafficking. The aim of this study was to investigate whether compounds that rescue CFTR F508del trafficking are capable of improving p.I661T-ATP8B1 plasma membrane expression. METHODS: The effect of CFTR corrector compounds on plasma membrane expression of p.I661T-ATP8B1 was evaluated by cell surface biotinylation and immunofluorescence. ATPase activity was evaluated of a purified analogue protein carrying a mutation at the matching position (p.L622T-ATP8A2). RESULTS: The clinically used compounds, 4 phenylbutyric acid (4-PBA), suberoylanilide hydroxamic acid (SAHA) and N butyldeoxynojirimycin (NB-DNJ) improved p.I661T-ATP8B1 plasma membrane targeting. Compounds C4, C5, C13 and C17 also significantly increased plasma membrane expression of p.I661T-ATP8B1. SAHA and compound C17 upregulated ATP8B1 transcription. p.I661T-ATP8B1 was partly targeted to the canalicular membrane in polarized cells, which became more evident upon treatment with SAHA and/or C4. p.L622T-ATP8A2 showed phospholipid-induced ATPase activity, suggesting that mutations at a matching position in ATP8B1 do not block functionality. Combination therapy of SAHA and compound C4 resulted in an additional improvement of ATP8B1 cell surface abundance. CONCLUSIONS: This study shows that several CFTR correctors can improve trafficking of p.I661T-ATP8B1 to the plasma membrane in vitro. Hence, these compounds may be suitable to be part of a future therapy for ATP8B1 deficiency and other genetic disorders associated with protein misfolding. LAY SUMMARY: Compounds that improve the cellular machinery dealing with protein homeostasis (proteostasis) and allow for proper folding of proteins with (mild) missense mutations are called proteostasis regulators (Balch, Science 2008). Such compounds are potentially of high therapeutic value for many (liver) diseases. In this manuscript, we investigated whether compounds identified in screens as CFTR folding correctors are actually proteostasis regulators and thus have a broader application in other protein folding diseases. Using these compounds, we could indeed show improved trafficking to the (apical) plasma membrane of a mutated ATP8B1 protein, carrying the p.I661T missense mutation. This is the most frequently identified mutation in this rare cholestatic disorder. Importantly, ATP8B1 shows no similarity to CFTR. These data are important in providing support for the concept that rare, genetic liver diseases can potentially be treated using a generalized strategy. PMID- 26879109 TI - Self-defined residential neighbourhoods: size variations and correlates across five European urban regions. AB - The neighbourhood is recognized as an important unit of analysis in research on the relation between obesogenic environments and development of obesity. One important challenge is to define the limits of the residential neighbourhood, as perceived by study participants themselves, in order to improve our understanding of the interaction between contextual features and patterns of obesity. An innovative tool was developed in the framework of the SPOTLIGHT project to identify the boundaries of neighbourhoods as defined by participants in five European urban regions. The aims of this study were (i) to describe self-defined neighbourhood (size and overlap with predefined residential area) according to the characteristics of the sampling administrative neighbourhoods (residential density and socioeconomic status) within the five study regions and (ii) to determine which individual or/and environmental factors are associated with variations in size of self-defined neighbourhoods. Self-defined neighbourhood size varies according to both individual factors (age, educational level, length of residence and attachment to neighbourhood) and contextual factors. These findings have consequences for how residential neighbourhoods are defined and operationalized and can inform how self-defined neighbourhoods may be used in research on associations between contextual characteristics and health outcomes such as obesity. PMID- 26879110 TI - Neighbourhood typology based on virtual audit of environmental obesogenic characteristics. AB - Virtual audit (using tools such as Google Street View) can help assess multiple characteristics of the physical environment. This exposure assessment can then be associated with health outcomes such as obesity. Strengths of virtual audit include collection of large amount of data, from various geographical contexts, following standard protocols. Using data from a virtual audit of obesity-related features carried out in five urban European regions, the current study aimed to (i) describe this international virtual audit dataset and (ii) identify neighbourhood patterns that can synthesize the complexity of such data and compare patterns across regions. Data were obtained from 4,486 street segments across urban regions in Belgium, France, Hungary, the Netherlands and the UK. We used multiple factor analysis and hierarchical clustering on principal components to build a typology of neighbourhoods and to identify similar/dissimilar neighbourhoods, regardless of region. Four neighbourhood clusters emerged, which differed in terms of food environment, recreational facilities and active mobility features, i.e. the three indicators derived from factor analysis. Clusters were unequally distributed across urban regions. Neighbourhoods mostly characterized by a high level of outdoor recreational facilities were predominantly located in Greater London, whereas neighbourhoods characterized by high urban density and large amounts of food outlets were mostly located in Paris. Neighbourhoods in the Randstad conurbation, Ghent and Budapest appeared to be very similar, characterized by relatively lower residential densities, greener areas and a very low percentage of streets offering food and recreational facility items. These results provide multidimensional constructs of obesogenic characteristics that may help target at-risk neighbourhoods more effectively than isolated features. PMID- 26879111 TI - Mismatch between perceived and objectively measured environmental obesogenic features in European neighbourhoods. AB - Findings from research on the association between the built environment and obesity remain equivocal but may be partly explained by differences in approaches used to characterize the built environment. Findings obtained using subjective measures may differ substantially from those measured objectively. We investigated the agreement between perceived and objectively measured obesogenic environmental features to assess (1) the extent of agreement between individual perceptions and observable characteristics of the environment and (2) the agreement between aggregated perceptions and observable characteristics, and whether this varied by type of characteristic, region or neighbourhood. Cross sectional data from the SPOTLIGHT project (n = 6037 participants from 60 neighbourhoods in five European urban regions) were used. Residents' perceptions were self-reported, and objectively measured environmental features were obtained by a virtual audit using Google Street View. Percent agreement and Kappa statistics were calculated. The mismatch was quantified at neighbourhood level by a distance metric derived from a factor map. The extent to which the mismatch metric varied by region and neighbourhood was examined using linear regression models. Overall, agreement was moderate (agreement < 82%, kappa < 0.3) and varied by obesogenic environmental feature, region and neighbourhood. Highest agreement was found for food outlets and outdoor recreational facilities, and lowest agreement was obtained for aesthetics. In general, a better match was observed in high-residential density neighbourhoods characterized by a high density of food outlets and recreational facilities. Future studies should combine perceived and objectively measured built environment qualities to better understand the potential impact of the built environment on health, particularly in low residential density neighbourhoods. PMID- 26879112 TI - Exploring why residents of socioeconomically deprived neighbourhoods have less favourable perceptions of their neighbourhood environment than residents of wealthy neighbourhoods. AB - Residents of socioeconomically deprived areas perceive their neighbourhood as less conducive to healthy behaviours than residents of more affluent areas. Whether these unfavourable perceptions are based on objective neighbourhood features or other factors is poorly understood. We examined individual and contextual correlates of socioeconomic inequalities in neighbourhood perceptions across five urban regions in Europe. Data were analysed from 5205 participants of the SPOTLIGHT survey. Participants reported perceptions of their neighbourhood environment with regard to aesthetics, safety, the presence of destinations and functionality of the neighbourhood, which were summed into an overall neighbourhood perceptions score. Multivariable multilevel regression analyses were conducted to investigate whether the following factors were associated with socioeconomic inequalities in neighbourhood perceptions: objectively observed neighbourhood features, neighbourhood social capital, exposure to the neighbourhood, self-rated health and lifestyle behaviours. Objectively observed traffic safety, aesthetics and the presence of destinations in the neighbourhood explained around 15% of differences in neighbourhood perceptions between residents of high and low neighbourhoods; levels of neighbourhood social cohesion explained around 52%. Exposure to the neighbourhood, self-rated health and lifestyle behaviours were significant correlates of neighbourhood perceptions but did not contribute to socioeconomic differences. This cross-European study provided evidence that socioeconomic differences in neighbourhood perceptions are not only associated with objective neighbourhood features but also with social cohesion. Levels of physical activity, sleep duration, self-rated health, happiness and neighbourhood preference were also associated with neighbourhood perceptions. PMID- 26879113 TI - Perceived environmental correlates of cycling for transport among adults in five regions of Europe. AB - Regular cycling for transport is an important potential contributor to daily physical activity among adults. Characteristics of the physical environment are likely to influence cycling for transport. The current study investigated associations between perceived physical environmental neighbourhood factors and adults' cycling for transport across five urban regions across Europe, and whether such associations were moderated by age, gender, education and urban region. A total of 4,612 adults from five European regions provided information about their transport-related cycling and their neighbourhood physical environmental perceptions in an online survey. Hurdle models adjusted for the clustering within neighbourhoods were performed to estimate associations between perceived physical environmental neighbourhood factors and odds of engaging in cycling for transport and minutes of cycling for transport per week. Inhabitants of neighbourhoods that were perceived to be polluted, having better street connectivity, having lower traffic speed levels and being less pleasant to walk or cycle in had higher levels of cycling for transport. Moderation analyses revealed only one interaction effect by gender. This study indicates that cycling for transport is associated with a number of perceived physical environmental neighbourhood factors across five urban regions across Europe. Our results indicated that the majority of the outcomes identified were valid for all subgroups of age, gender, education and across regions in the countries included in the study. PMID- 26879114 TI - The relation between sleep duration and sedentary behaviours in European adults. AB - Too much sitting, and both short and long sleep duration are associated with obesity, but little is known on the nature of the relations between these behaviours. We therefore examined the associations between sleep duration and time spent sitting in adults across five urban regions in Europe. We used cross sectional survey data from 6,037 adults (mean age 51.9 years (SD 16.4), 44.0% men) to assess the association between self-reported short (<6 h per night), normal (6-8 h per night) and long (>8 h per night) sleep duration with self report total time spent sitting, time spent sitting at work, during transport, during leisure and while watching screens. The multivariable multilevel linear regression models were tested for moderation by urban region, age, gender, education and weight status. Because short sleepers have more awake time to be sedentary, we also used the percentage of awake time spent sedentary as an outcome. Short sleepers had 26.5 min day(-1) more sedentary screen time, compared with normal sleepers (CI 5.2; 47.8). No statistically significant associations were found with total or other domains of sedentary behaviour, and there was no evidence for effect modification. Long sleepers spent 3.2% higher proportion of their awake time sedentary compared with normal sleepers. Shorter sleep was associated with increased screen time in a sample of European adults, irrespective of urban region, gender, age, educational level and weight status. Experimental studies are needed to assess the prospective relation between sedentary (screen) time and sleep duration. PMID- 26879115 TI - Interactions of individual perceived barriers and neighbourhood destinations with obesity-related behaviours in Europe. AB - Perceived barriers towards physical activity and healthy eating as well as local availability of opportunities (destinations in the neighbourhood) are important determinants of obesity-related behaviours in adults. Little is known, however, about how these factors interact with the behaviours. Data were analysed from 5,205 participants of the SPOTLIGHT survey, conducted in 60 neighbourhoods in urban regions of five different countries across Europe. A virtual audit was conducted to collect data on the presence of destinations in each neighbourhood. Direct associations of, and interactions between, the number of individual perceived barriers and presence of destinations with obesity-related behaviours (physical activity and dietary behaviours) were analysed using multilevel regression analyses, adjusted for key covariates. Perceiving more individual barriers towards physical activity and healthy eating was associated with lower odds of physical activity and healthy eating. The presence of destinations such as bicycle lanes, parks and supermarkets was associated with higher levels of physical activity and healthier dietary behaviours. Analyses of additive interaction terms suggested that the interaction of destinations and barriers was competitive, such that the presence of destinations influenced obesity-related behaviours most among those perceiving more barriers. These explorative findings emphasize the interest and importance of combining objective (e.g. virtual neighbourhood audit) methods and subjective (e.g. individual perceived barriers collected in a survey) to better understand how the characteristics of the residential built environment can shape obesity-related behaviours depending on individual characteristics. PMID- 26879116 TI - Psychosocial environment: definitions, measures and associations with weight status--a systematic review. AB - Socio-ecological models suggest that many elements of the social environment act as upstream determinants of obesity. This systematic review examined definitions, measures and strength of associations between the psychosocial environment and adult weight status. Studies were included if they were conducted on adults, the outcome was weight status, carried out in any developed country and investigated at least one psychosocial environmental construct. Six databases for primary studies were searched: EMBASE, MEDLINE, PsycINFO, Scopus, Web of Science and the Cochrane Library. We restricted our search to studies published in English between January 1995 and February 2015. An adapted 'Quality Assessment Tool for Quantitative Studies' was used to evaluate risk of bias of included studies. Out of 14,784 screened records, 42 articles were assessed using full text. A total of 19 studies were included. The strongest associations with weight status were found for social capital and collective efficacy, although few studies found significant associations. There was heterogeneity in the definitions and metrics of psychosocial environmental constructs. There is limited evidence that greater social capital and collective efficacy are associated with healthier weight status. The research conducted to date has not robustly identified relations. We highlight challenges to undertaking research and establishing causality in this field and provide recommendations for further research. PMID- 26879117 TI - Neighbourhood social capital: measurement issues and associations with health outcomes. AB - We compared ecometric neighbourhood scores of social capital (contextual variation) to mean neighbourhood scores (individual and contextual variation), using several health-related outcomes (i.e. self-rated health, weight status and obesity-related behaviours). Data were analysed from 5,900 participants in the European SPOTLIGHT survey. Factor analysis of the 13-item social capital scale revealed two social capital constructs: social networks and social cohesion. The associations of ecometric and mean neighbourhood-level scores of these constructs with self-rated health, weight status and obesity-related behaviours were analysed using multilevel regression analyses, adjusted for key covariates. Analyses using ecometric and mean neighbourhood scores, but not mean neighbourhood scores adjusted for individual scores, yielded similar regression coefficients. Higher levels of social network and social cohesion were not only associated with better self-rated health, lower odds of obesity and higher fruit consumption, but also with prolonged sitting and less transport-related physical activity. Only associations with transport-related physical activity and sedentary behaviours were associated with mean neighbourhood scores adjusted for individual scores. As analyses using ecometric scores generated the same results as using mean neighbourhood scores, but different results when using mean neighbourhood scores adjusted for individual scores, this suggests that the theoretical advantage of the ecometric approach (i.e. teasing out individual and contextual variation) may not be achieved in practice. The different operationalisations of social network and social cohesion were associated with several health outcomes, but the constructs that appeared to represent the contextual variation best were only associated with two of the outcomes. PMID- 26879118 TI - The way ahead: where next for research into obesogenic environments? PMID- 26879119 TI - Micellar electrokinetic chromatographic method for the dabrafenib determination in biological samples. AB - Two different micellar electrokinetic chromatographic methods to determine dabrafenib in urine and serum, both using borate buffer (pH 9.2, 20 mM) and SDS as separation electrolyte, are developed and validated. The analyses were carried out in a fused-silica capillary of 75 MUm of internal diameter and total length of 47 and 37 cm for urine and serum determination, respectively. The detection of the target compound was performed at 227 nm in urine samples and at 251 nm in serum samples. The linearity range was from 1 to 21 mg/L of dabrafenib in urine and from 2 to 40 mg/L in serum. In all cases, inter- and intraday RSDs were <4%. Sample preparation of serum samples consists of an only step of 1:1 dilution with water before its injection in the electrophoretic system. These simple, sensitive, accurate, and cost-effective methods can be used in routine clinical practice to monitor dabrafenib concentrations in urine and serum of metastatic melanoma skin cancer patients. PMID- 26879120 TI - Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment. AB - BACKGROUND: This study aimed to investigate the development of opioid tolerance in patients receiving long-term methadone maintenance treatment (MMT). METHODS: A region-wide cross-sectional study was performed focusing on dosage and duration of treatment. Differences between racemic methadone and levomethadone were examined. All 20 psychiatric hospitals and all 110 outpatient clinics in Berlin licensed to offer MMT were approached in order to reach patients under MMT fulfilling the DSM IV criteria of opiate dependence. In the study, 720 patients treated with racemic methadone or levomethadone gave information on the dosage of treatment. Out of these, 679 patients indicated the duration of MMT. RESULTS: Treatment with racemic methadone was reported for 370 patients (54.5%), with levomethadone for 309 patients (45.5%). Mean duration of MMT was 7.5 years. We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately. These effects remained significant when only patients receiving MMT for 1 year or longer were considered, indicating proceeding tolerance development in long-term treatment. When correlations were compared between racemic methadone and levomethadone, no significant difference was found. CONCLUSIONS: Our data show a tolerance development under long-term treatment with both racemic methadone and levomethadone. Tolerance development did not differ significantly between the two substances. PMID- 26879121 TI - Outcomes of revision endoscopic modified Lothrop procedure. AB - BACKGROUND: Endoscopic modified Lothrop procedure (EMLP) is used to treat patients who fail conventional sinus surgery. The failure rate of a primary EMLP is reported to be between 5% and 32%. The failure rate of revision EMLP has not been reported. We present our institutions data regarding the outcome of patients requiring revision EMLP. METHODS: Data was collected prospectively. Patients undergoing primary EMLP between January 2001 and December 2013 with a minimum follow-up of 6 months were included. Information related to demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22) score, Lund-Mackay scores, intraoperative findings, and endoscopic ostium assessment were collected. RESULTS: There were 213 primary EMLPs completed with average follow-up of 36 months. The failure rate of primary EMLP was 8.9% (19/213), whereas the failure rate of revision EMLP was 21% (4/19). Risk factors for failure of primary EMLP included the presence of intraoperative pus, more than 5 previous sinus operations and aspirin-exacerbated respiratory disease (AERD). Revision of EMLP was undertaken primarily due to recurrence of nasal polyps or ostium stenosis. Those patients who underwent revision EMLP experienced symptomatic improvement and no major complications following the procedure. CONCLUSION: The failure rate of revision EMLP is 21% in our series. The majority of revisions were for nasal polyp recurrence. Revision EMLP is a safe and well tolerated procedure in the small group of patients that require further surgery. Patients with intraoperative pus present at their initial EMLP, more than 5 previous sinus operations, or AERD are at increased risk of failure. PMID- 26879122 TI - Bladder telemetry: A new approach to evaluate micturition behavior under physiological and inflammatory conditions. AB - AIMS: To establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions. METHODS: The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide. RESULTS: The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control. CONCLUSION: This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol. Urodynam. 36:308-315, 2017. (c) 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc. PMID- 26879124 TI - One-Pot Synthesis of Pomegranate-Structured Fe3 O4 /Carbon Nanospheres-Doped Graphene Aerogel for High-Rate Lithium Ion Batteries. AB - A unique hierarchically nanostructured composite of iron oxide/carbon (Fe3O4/C) nanospheres-doped three-dimensional (3D) graphene aerogel has been fabricated by a one-pot hydrothermal strategy. In this novel nanostructured composite aerogel, uniform Fe3O4 nanocrystals (5-10 nm) are individually embedded in carbon nanospheres (ca. 50 nm) forming a pomegranate-like structure. The carbon matrix suppresses the aggregation of Fe3O4 nanocrystals, avoids direct exposure of the encapsulated Fe3O4 to the electrolyte, and buffers the volume expansion. Meanwhile, the interconnected 3D graphene aerogel further serves to reinforce the structure of the Fe3O4/C nanospheres and enhances the electrical conductivity of the overall electrode. Therefore, the carbon matrix and the interconnected graphene network entrap the Fe3O4 nanocrystals such that their electrochemical function is retained even after fracture. This novel hierarchical aerogel structure delivers a long-term stability of 634 mA h g(-1) over 1000 cycles at a high current density of 6 A g(-1) (7 C), and an excellent rate capability of 413 mA h g(-1) at 10 A g(-1) (11 C), thus exhibiting great potential as an anode composite structure for durable high-rate lithium-ion batteries. PMID- 26879123 TI - Isolation and genome sequencing of four Arctic marine Psychrobacter strains exhibiting multicopper oxidase activity. AB - BACKGROUND: Marine cold-temperature environments are an invaluable source of psychrophilic microbial life for new biodiscoveries. An Arctic marine bacterial strain collection was established consisting of 1448 individual isolates originating from biota, water and sediment samples taken at a various depth in the Barents Sea, North of mainland Norway, with an all year round seawater temperature of 4 degrees C. The entire collection was subjected to high throughput screening for detection of extracellular laccase activity with guaiacol as a substrate. RESULTS: In total, 13 laccase-positive isolates were identified, all belonging to the Psychrobacter genus. From the most diverse four strains, based on 16S rRNA gene sequence analysis, all originating from the same Botryllus sp. colonial ascidian tunicate sample, genomic DNA was isolated and genome sequenced using a combined approach of whole genome shotgun and 8 kb mate pair library sequencing on an Illumina MiSeq platform. The genomes were assembled and revealed genome sizes between 3.29 and 3.52 Mbp with an average G + C content of around 42%, with one to seven plasmids present in the four strains. Bioinformatics based genome mining was performed to describe the metabolic potential of these four strains and to identify gene candidates potentially responsible for the observed laccase-positive phenotype. Up to two different laccase-like multicopper oxidase (LMCO) encoding gene candidates were identified in each of the four strains. Heterologous expression of P11F6-LMCO and P11G5 LMCO2 in Escherichia coli BL21 (DE3) resulted in recombinant proteins exhibiting 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and guaiacol oxidizing activity. CONCLUSIONS: Thirteen Psychrobacter species with laccase positive phenotype were isolated from a collection of Arctic marine bacteria. Four of the isolates were genome sequenced. The overall genome features were similar to other publicly available Psychrobacter genome sequences except for P11G5 harboring seven plasmids. However, there were differences at the pathway level as genes associated with degradation of phenolic compounds, nicotine, phenylalanine, styrene, ethylbenzene, and ethanolamine were detected only in the Psychrobacter strains reported in this study while they were absent among the other publicly available Psychrobacter genomes. In addition, six gene candidates were identified by genome mining and shown to possess T1, T2 and T3 copper binding sites as the main signature of the three-domain laccases. P11F6-LMCO and P11G5-LMCO2 were recombinantly expressed and shown to be active when ABTS and guaiacol were used as substrates. PMID- 26879125 TI - FeOOH/Co/FeOOH Hybrid Nanotube Arrays as High-Performance Electrocatalysts for the Oxygen Evolution Reaction. AB - Herein, we developed FeOOH/Co/FeOOH hybrid nanotube arrays (HNTAs) supported on Ni foams for oxygen evolution reaction (OER). The inner Co metal cores serve as highly conductive layers to provide reliable electronic transmission, and can overcome the poor electrical conductivity of FeOOH efficiently. DFT calculations demonstrate the strong electronic interactions between Co and FeOOH in the FeOOH/Co/FeOOH HNTAs, and the hybrid structure can lower the energy barriers of intermediates and thus promote the catalytic reactions. The FeOOH/Co/FeOOH HNTAs exhibit high electrocatalytic performance for OER, such as low onset potential, small Tafel slope, and excellent long-term durability, and they are promising electrocatalysts for OER in alkaline solution. PMID- 26879126 TI - Future options of anti-angiogenic cancer therapy. AB - In human patients, drugs that block tumor vessel growth are widely used to treat a variety of cancer types. Many rigorous phase 3 clinical trials have demonstrated significant survival benefits; however, the addition of an anti angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer patients. Currently, it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients. In this article, we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens. PMID- 26879127 TI - Parent perspectives and reasons for lower urgency paediatric presentations to emergency departments. AB - OBJECTIVE: The age band with, by far, the greatest number of ED presentations is children 0-4 years, with other paediatric age bands also among the highest. As the majority of these presentations are for lower urgency conditions, we sought to determine why parents seek ED care for their child for lower urgency conditions. METHODS: A survey study of 1150 parents or guardians of children with lower urgency conditions (triage category 4 or 5) presenting to the EDs of three public general and one paediatric specialty hospital in metropolitan Melbourne. RESULTS: Fewer than half of parents (43%) attempted to make an appointment with a general practitioner (GP) for their child prior to presenting to the ED. Two thirds of those who did contact a GP were instructed by their GP to go to the ED for their lower urgency condition. Few attempted to contact a nurse telephone triage service or after-hours GP service. CONCLUSIONS: The current magnitude and the growth of lower urgency paediatric ED presentations is a strain on the health care system. Efforts to educate parents regarding the suitability and availability of GP appointments can be the cornerstone of an initial strategy to address this issue. However, efforts to address the high rates of GP referral to EDs for low urgency presentations will be more vexing to develop, yet no less important. They will require addressing fundamental issues in both current GP care for children and the training of GP registrars. PMID- 26879128 TI - Quantitative and qualitative evaluation of kernel anthocyanins from southwestern United States blue corn. AB - BACKGROUND: Anthocyanin-rich blue corn is an emerging specialty crop in the USA. The antioxidant properties of blue corn offer health benefits in the human diet. The objectives of this study were to identify, characterize and quantify the anthocyanins from blue corn. Hypotheses tested were that total anthocyanin content was similar among southwestern US accessions and that it would vary across locations. It was also examined whether different anthocyanin components were unique to certain genotypes. RESULTS: Across all locations and accessions, an average of 0.43 g kg(-1) total anthocyanin content (TAC) was observed. Accessions Santa Clara Blue and Ohio Blue displayed the highest TAC. The TAC of accession Flor del Rio was lower by nearly a factor of six. A total of five anthocyanin components were identified. Cyanidin 3-glucoside was the most abundant, followed by pelargonidin and peonidin 3-glucoside. Succinyl and disuccinyl glycosidic forms of cyanidin were also identified. Cyanidin 3 disuccinylglucoside was newly identified as a novel form of anthocyanin. CONCLUSION: Quantitative and qualitative anthocyanin expression was determined to be relatively stable across multiple southwestern environments. Increased expression of red and purple pigmentation in accession Flor del Rio appeared to be associated more with reduced TAC and cyanidin 3-glucoside than with elevated pelargonidin per se. A previously unreported anthocyanin component in blue corn, cyanidin 3-disuccinylglucoside, is present in southwestern landraces. (c) 2016 Society of Chemical Industry. PMID- 26879129 TI - Interleukin 1alpha-induced disruption of the Sertoli cell cytoskeleton affects gap junctional communication. AB - Gap junctions (GJ) are transmembrane channels that connect the cytoplasms of adjacent cells, thereby facilitating the rapid exchange of ions, second messengers, and metabolites smaller than 1kDa. Connexin 43, the best-studied GJ protein, is a component of the Sertoli cell barrier/blood-testis barrier (BTB). To gain insight into the biology of the BTB, we investigated the effects of interleukin 1alpha (IL1A), a pro-inflammatory cytokine that disrupts BTB function, on gap junctional communication (GJC) in Sertoli cells. Compared with controls, the levels of connexin 43 and connexin 43 (Ser 368) increased ~30- and 20-fold, respectively, at 24 h after IL1A treatment. To assess GJ function, we investigated fluorescence recovery in photobleached Sertoli cells after vehicle or IL1A treatment. Compared with the control, IL1A affected the ability of calcein to return to photobleached cells, indicating that GJC was compromised. To explain the effects of IL1A on GJ function, the involvement of the Sertoli cell cytoskeleton was investigated. Stress fibers aggregated at the periphery of Sertoli cells treated with IL1A. These results were substantiated by a biochemical assay that showed IL1A to disrupt the bundling of exogenous F-actin by Sertoli cells. In summary, IL1A regulates GJC in Sertoli cells, which is critical for BTB restructuring. PMID- 26879130 TI - Flow-induced translocation of star polymers through a nanopore. AB - We study the flow-induced translocation of the star polymers through a nanopore using a hybrid simulation method that incorporates a lattice-Boltzmann approach for the fluid into a molecular dynamics model for the polymer. Our simulation demonstrates the existence of an optimal forward arm number of the star polymers captured by the nanopore, and illustrates its significance in determining the critical velocity flux of the star polymer translocation through the nanopore. Importantly, we find that the critical velocity flux of the star polymers is independent of the arm polymerization degree, but exhibits a linear dependence on the arm number. Based on previous scaling arguments and our simulation results, we conclude a linear dependence of the critical velocity flux on the arm number of the star polymers, which can successfully describe the dynamics of the star polymer translocation. Our simulation results rationalize the experimental results for the dependence of the critical velocity flux on the arm polymerization degree and the arm number of the star polymers, which provide new insights for the characterization and the purification of the star polymers. PMID- 26879131 TI - Profiling microRNA expression during fracture healing. AB - BACKGROUND: The discovery of microRNA (miRNA) has revealed a novel type of regulatory control for gene expression. Increasing evidence suggests that miRNA regulates chondrocyte, osteoblast, and osteoclast differentiation and function, indicating miRNA as key regulators of bone formation, resorption, remodeling, and repair. We hypothesized that the functions of certain miRNAs and changes to their expression pattern may play crucial roles during the process of fracture healing. METHODS: Standard healing fractures and unhealing fractures produced by periosteal cauterization at the fracture site were created in femurs of seventy rats, with half assigned to the standard healing fracture group and half assigned to the nonunion group. At post-fracture days 3, 7, 10, 14, 21, and 28, total RNA including miRNA was extracted from the newly generated tissue at the fracture site. Microarray analysis was performed with miRNA samples from each group on post-fracture day 14. For further analysis, we selected highly up-regulated five miRNAs in the standard healing fracture group from the microarray data. Real-time PCR was performed with miRNA samples at each time point above mentioned to compare the expression levels of the selected miRNAs between standard healing fractures and unhealing fractures and investigate their time-course changes. RESULTS: Microarray and real-time polymerase chain reaction (PCR) analyses on day 14 revealed that five miRNAs, miR-140-3p, miR-140-5p, miR-181a-5p, miR-181d-5p, and miR-451a, were significantly highly expressed in standard healing fractures compared with unhealing fractures. Real-time PCR analysis further revealed that in standard healing fractures, the expression of all five of these miRNAs peaked on day 14 and declined thereafter. CONCLUSION: Our results suggest that the five miRNAs identified using microarray and real-time PCR analyses may play important roles during fracture healing. These findings provide valuable information to further understand the molecular mechanism of fracture healing and may lead to the development of miRNA-based tissue engineering strategies to promote fracture healing. PMID- 26879132 TI - Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer. AB - BACKGROUND: An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer. Moreover, methylation of miR-34a CpG Islands was found to down-regulate miR-34a expression. The aim of this study was to investigate the clinical relevance of mir34a as well as its promoter methylation in a subset of 133 ovarian cancers with a special focus on the p53 mutation status, the dualistic type I and type II ovarian cancer model and the different histotypes. METHODS: One hundred thirty-three epithelial ovarian cancers and 8 samples of healthy ovarian surface epithelium were retrospectively analysed for miR-34a expression with quantitative real-time reverse transcription PCR (qRT-PCR). Gene specific DNA methylation was evaluated with MethyLight technique. RESULTS: Significantly lower miR-34a expression was found in ovarian cancers than in healthy ovarian epithelium (p = 0.002). The expression of miR-34a was found lower in type II than in type I cancers (p = 0.037), in p53 mutated as compared to p53 wild type cancers (p = 0.003) and in high grade compared to in low grade cancers (p = 0.028). In multivariate COX regression model low expressing miR-34a cancers exhibited a reduced PFS (p = 0.039) and OS (p = 0.018). In serous cancers low miR 34a levels showed a worse OS confirmed also in multivariate analysis (p = 0.022). miR-34a promoter methylation was found higher in type II cancers than in type I (p = 0.006). mir34a expression and promoter methylation showed an inverse correlation in cancer samples (p = 0.05). CONCLUSION: We demonstrated a clinical independent role of miR-34a in epithelial ovarian cancers. Moreover, we corroborated the correlation between miR-34a expression and its promoter methylation in a large set of ovarian cancers. The inverse association between miR-34a expression and grading, p53 mutation status and dualistic tumor type classification, together with its prognostic relevance may underline the tumor suppressive character of miR-34a in ovarian cancer. PMID- 26879134 TI - Iodoindazoles with Selective Magnesiation at Position 3: A Route to Highly Functionalized Indazoles. AB - A unique route to highly functionalized indazoles is described. A regioselective magnesiation at position 3 of 4-, 5-, 6- and 7-iodo-2-THP-indazoles (THP=tetrahydropyranyl) has been developed using TMPMgCl?LiCl (TMP=2,2,6,6 tetramethylpiperidyl). The obtained magnesiate can be trapped by different electrophiles to introduce a wide range of functional groups including halogens, thioalkyls, alcohols, aldehydes, ketones, amides, or esters at position 3. Once this position is functionalized, the iodine atoms can be further reacted through metal-halogen exchange or cross-coupling strategies. Finally, N-substitution reactions allow the synthesis of a variety of highly functionalized indazoles giving access to these valuable scaffolds through a simple and unique route. PMID- 26879135 TI - The ultra-rapid synthesis of 2D graphitic carbon nitride nanosheets via direct microwave heating for field emission. AB - The 2D g-C3N4 nanosheets were ultra-rapidly prepared via a direct microwave heating approach. The as-synthesized g-C3N4 possessed a large surface area, few stacking layers, a large aspect ratio and an enlarged bandgap. As a consequence, the excellent field emission properties of 2D g-C3N4 nanosheets were exhibited with extremely low turn-on fields. PMID- 26879133 TI - Parkinson's disease-related fatigue: A case definition and recommendations for clinical research. AB - Fatigue is one of the most common and disabling symptoms in Parkinson's disease (PD). Since fatigue was first described as a common feature of PD 20 years ago, little progress has been made in understanding its causes or treatment. Importantly, PD patients attending the 2013 World Parkinson Congress voted fatigue as the leading symptom in need of further research. In response, the Parkinson Disease Foundation and ProjectSpark assembled an international team of experts to create recommendations for clinical research to advance this field. The working group identified several areas in which shared standards would improve research quality and foster progress including terminology, diagnostic criteria, and measurement. Terminology needs to (1) clearly distinguish fatigue from related phenomena (eg, sleepiness, apathy, depression); (2) differentiate subjective fatigue complaints from objective performance fatigability; and (3) specify domains affected by fatigue and causal factors. We propose diagnostic criteria for PD-related fatigue to guide participant selection for clinical trials and add rigor to mechanistic studies. Recommendations are made for measurement of subjective fatigue complaints, performance fatigability, and neurophysiologic changes. We also suggest areas in which future research is needed to address methodological issues and validate or optimize current practices. Many limitations in current PD-related fatigue research may be addressed by improving methodological standards, many of which are already being successfully applied in clinical fatigue research in other medical conditions (eg, cancer, multiple sclerosis). (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26879136 TI - Cubic Polyhedral Oligomeric Silsesquioxane Based Functional Materials: Synthesis, Assembly, and Applications. AB - Organically modified cubic polyhedral oligomeric silsesquioxanes (POSS) have attracted increasing attention in the design of novel functional hybrid materials for applications such as porous materials, liquid crystals, semiconductors, high temperature lubricants, fuel cells, and lithium batteries. The nanosized POSS moiety can be conveniently modified on the periphery with a variety of functional groups to lead to hybrid materials with desired functions. In addition, suitable mono-functionalized POSS derivatives can be incorporated into polymers as side chains via various synthetic strategies to offer a wide class of functional polymeric materials with tunable physical properties for targeted applications. In this Focus Review, we aim to summarize the recent developments on the chemistry and applications of POSS-based molecules and polymers. Moreover, the properties as well as assembly behavior of the POSS-based functional hybrid materials will be reviewed, and the relationship of the performance of the hybrid materials with the intrinsic nature of the POSS unit will be addressed. PMID- 26879137 TI - Interviewing people with dementia in hospital: recommendations for researchers. AB - AIMS AND OBJECTIVES: This article aims to: Discuss the inclusion of the perspectives of people with dementia in research. Consider the major challenges involved in the process of interviewing people with dementia. Provide recommendations for those involved in interviewing people with dementia in hospital. BACKGROUND: People with dementia are frequent consumers of health care and often have a poor experience in hospital but have been largely excluded from direct participation in research until recently. Limited understanding of the specific communication needs of people with dementia restricts access to the person's viewpoint. Recommendations for interviewers which consider the specific requirements of people with dementia are presented. DESIGN/METHOD: This is a discursive article drawing on the experience of interviewing people with dementia in three separate studies. The conclusions that will be discussed are recommendations for researchers which were formulated following examination of the reflective journals written during the data collection phases of the studies and analysis of the data from the perspective of interviewer performance. RESULTS: Six main issues have been identified and discussed with reference to Habermas's theory of communicative action. CONCLUSIONS: Interviewing people with dementia requires specific skills including an ability to be emotionally sensitive and respectful of the person. This engagement can be challenging and complex for the interviewer. It is vital that genuine engagement and mutual recognition are established before the interview is attempted. A more meaningful research outcome is likely to be the result. RELEVANCE TO CLINICAL PRACTICE: The suggestions outlined here are relevant to a variety of people who are in contact with people with dementia in clinical settings. Developing the skills of researchers in this area needs a commitment by organisations to promote the inclusion of the perceptions of people with dementia in research and in discussions about their own care. PMID- 26879138 TI - Low toxic and high soluble camptothecin derivative 2-47 effectively induces apoptosis of tumor cells in vitro. AB - The cytotoxic activity of camptothecin derivatives is so high that these compounds need to be further modified before their successful application as anti cancer agents clinically. In this study, we reported the synthesis and biological evaluation of a novel camptothecin derivative called compound 2-47. The changes in structure did not reduce its activity to inhibit DNA topoisomerase I. Compound 2-47 induced apoptosis of many tumor cells including leukemia cells K562, Jurkat, HL-60, breast cancer cell BT-549, colon cancer cell HT-29 and liver cancer cell HepG2 with a half maximal inhibitory concentration (IC50) of 2- to 3-fold lower than HCPT as a control. In particular, 2-47 inhibited the proliferation of Jurkat cells with an IC50 of as low as 40 nM. By making use of Jurkat cell as a model, following treatment of Jurkat cells, compound 2-47 activated caspase-3 and PARP, resulting in a decreased Bcl-2/Bax ratio. These data showed that compound 2-47 induces Jurkat cell death through the mitochondrial apoptotic pathway. In addition, compound 2-47 showed a decreased cytotoxic activity against normal cells and an improved solubility in low-polar solvent. For example, compound 2-47 solutes in CHCl3 130-fold higher than HCPT. Taken together, our data demonstrated that camptothecin derivative 2-47 notably inhibits the tumor cell proliferation through mitochondrial-mediated apoptosis in vitro. PMID- 26879139 TI - Amphipathic polyproline peptides stimulate cholesterol efflux by the ABCA1 transporter. AB - ApoA-I mimetics are short synthetic peptides that contain an amphipathic alpha helix and stimulate cholesterol efflux by the ABCA1 transporter in a detergent like extraction mechanism. We investigated the use of amphipathic peptides with a polypro helix for stimulating cholesterol efflux by ABCA1. Polypro peptides were synthesized with modified prolines, containing either a hydrophobic phenyl group (Prop) or a polar N-acetylgalactosamine (Prog) attached to the pyrrolidine ring and were designated as either PP-2, 3, 4, or 5, depending on the number of 3 amino acid repeat units (Prop-Prog-Prop). Based on molecular modeling, these peptides were predicted to be relatively rigid and to bind to a phospholipid bilayer. By CD spectroscopy, PP peptides formed a Type-II polypro helix in an aqueous solution. PP-2 was inactive in promoting cholesterol efflux, but peptides with more than 2 repeat units were active. PP-4 showed a similar Vmax as a much longer amphipathic alpha-helical peptide, containing 37 amino acids, but had a Km that was approximately 20-fold lower. PP peptides were specific in that they did not stimulate cholesterol efflux from cells not expressing ABCA1 and were also non-cytotoxic. Addition of PP-3, 4 and 5 to serum promoted the formation of smaller size HDL species (7 nM) and increased its capacity for ABCA1-dependent cholesterol efflux by approximately 20-35% (p < 0.05). Because of their relatively small size and increased potency, amphipathic peptides with a polypro helix may represent an alternative structural motif for the development of apoA-I mimetic peptides. PMID- 26879140 TI - A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells. AB - CRISPR-Cas9 mediated genome editing system has been developed as a powerful tool for elucidating the function of genes through genetic engineering in multiple cells and organisms. This system takes advantage of a single guide RNA (sgRNA) to direct the Cas9 endonuclease to a specific DNA site to generate mutant alleles. Since the targeting efficiency of sgRNAs to distinct DNA loci can vary widely, there remains a need for a rapid, simple and efficient sgRNA selection method to overcome this limitation of the CRISPR-Cas9 system. Here we report a novel system to select sgRNA with high efficacy for DNA sequence modification by a luciferase assay. Using this sgRNAs selection system, we further demonstrated successful examples of one sgRNA for generating one gene knockout cell lines where the targeted genes are shown to be functionally defective. This system provides a potential application to optimize the sgRNAs in different species and to generate a powerful CRISPR-Cas9 genome-wide screening system with minimum amounts of sgRNAs. PMID- 26879141 TI - Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization. AB - Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. PMID- 26879142 TI - Linoleic acid and stearic acid elicit opposite effects on AgRP expression and secretion via TLR4-dependent signaling pathways in immortalized hypothalamic N38 cells. AB - The regulation of food intake is a promising way to combat obesity. It has been implicated that various fatty acids exert different effects on food intake and body weight. However, the underlying mechanism remains poorly understood. The aim of the present study was to investigate the effects of linoleic acid (LA) and stearic acid (SA) on agouti-related protein (AgRP) expression and secretion in immortalized mouse hypothalamic N38 cells and to explore the likely underlying mechanisms. Our results demonstrated that LA inhibited, while SA stimulated AgRP expression and secretion of N38 cells in a dose-dependent manner. In addition, LA suppressed the protein expression of toll-like receptor 4 (TLR4), phosphorylation levels of JNK and IKKalpha/beta, suggesting the inhibition of TLR4-dependent inflammation pathway. However, the above mentioned inhibitory effects of LA were eliminated by TLR4 agonist lipopolysaccharide (LPS). In contrast, SA promoted TLR4 protein expression and activated TLR4-dependent inflammation pathway, with elevated ratio of p-JNK/JNK. While TLR4 siRNA reversed the stimulatory effects of SA on AgRP expression and TLR4-dependent inflammation. Moreover, we found that TLR4 was also involved in LA-enhanced and SA-impaired leptin/insulin signal pathways in N38 cells. In conclusion, our findings indicated that LA elicited inhibitory while SA exerted stimulatory effects on AgRP expression and secretion via TLR4-dependent inflammation and leptin/insulin pathways in N38 cells. These data provided a better understanding of the mechanism underlying fatty acids regulated food intake and suggested the potential role of long-chain unsaturated fatty acids such as LA in reducing food intake and treating obesity. PMID- 26879143 TI - The importin protein karyopherin-beta1 regulates the mice fibroblast-like synoviocytes inflammation via facilitating nucleus transportation of STAT3 transcription factor. AB - Karyopherin-beta1 (KPNB1) which is an adaptor protein which transports several proteins to the nucleus. We study the functions and possible mechanisms of KPNB1 in collagen-induced arthritis (CIA). Western blotting and immunohistochemistry shows the protein expression of KPNB1 is increased in synovial tissue of CIA mice compared with the controls. Double immunofluorescent staining suggests that KPNB1 is expressed in CIA mice fibroblast-like synoviocytes (FLS). Moreover, the expression of KPNB1 in FLS is upregulated in time-dependent manner by IL-1beta stimulation. Both immunoprecipitation and immunofluorescent staining assay reveals the interaction between KPNB1 and STAT3 and their translocation from cytoplasm to nucleus in IL-1beta-treated FLS. Furthermore, suppression of KPNB1 inhibits IL-1beta-induced the nucleus expression of STAT3 in FLS and decreases the expression of IL-6 and MMP-1, leading to attenuation of FLS invasion. Finally, the transport function of KPNB1 is depended on KPNA2. Therefore, we infer that KPNB1 may play a key role in the inflammation process of RA via STAT3 signal transduction pathway. PMID- 26879144 TI - Improving brightness and photostability of green and red fluorescent proteins for live cell imaging and FRET reporting. AB - Many genetically encoded biosensors use Forster resonance energy transfer (FRET) to dynamically report biomolecular activities. While pairs of cyan and yellow fluorescent proteins (FPs) are most commonly used as FRET partner fluorophores, respectively, green and red FPs offer distinct advantages for FRET, such as greater spectral separation, less phototoxicity, and lower autofluorescence. We previously developed the green-red FRET pair Clover and mRuby2, which improves responsiveness in intramolecular FRET reporters with different designs. Here we report the engineering of brighter and more photostable variants, mClover3 and mRuby3. mClover3 improves photostability by 60% and mRuby3 by 200% over the previous generation of fluorophores. Notably, mRuby3 is also 35% brighter than mRuby2, making it both the brightest and most photostable monomeric red FP yet characterized. Furthermore, we developed a standardized methodology for assessing FP performance in mammalian cells as stand-alone markers and as FRET partners. We found that mClover3 or mRuby3 expression in mammalian cells provides the highest fluorescence signals of all jellyfish GFP or coral RFP derivatives, respectively. Finally, using mClover3 and mRuby3, we engineered an improved version of the CaMKIIalpha reporter Camuialpha with a larger response amplitude. PMID- 26879145 TI - Recombinant human bone morphogenetic protein-9 potently induces osteogenic differentiation of human periodontal ligament fibroblasts. AB - To accomplish effective periodontal regeneration for periodontal defects, several regenerative methods using growth and differentiation factors, including bone morphogenetic proteins (BMPs), have been developed. Bone morphogenetic protein-9 exhibits the most potent osteogenic activity of this growth factor family. However, it is unclear whether exogenous BMP-9 can induce osteogenic differentiation in human periodontal ligament (PDL) fibroblasts. Here, we examined the effects of recombinant human (rh) BMP-9 on osteoblastic differentiation in human PDL fibroblasts in vitro, compared with rhBMP-2. Recombinant human BMP-9 potently induced alkaline phosphatase (ALP) activity, mineralization, and increased expression of runt-related transcription factor 2/core binding factor alpha 1 (RUNX2/CBFA1), osterix, inhibitor of DNA binding/differentiation-1 (ID1), osteopontin, and bone sialoprotein genes, compared with rhBMP-2. The levels of rhBMP-9-induced osterix and ALP mRNA were significantly reduced in activin receptor-like kinase-1 and -2 small interfering RNA (siRNA)-transfected human PDL fibroblasts. Recombinant human BMP-9-induced ALP activity was not inhibited by noggin, in contrast to rhBMP-2 induced ALP activity, which was. Phosphorylation of SMAD1/5/8 in human PDL fibroblasts was induced by addition of rhBMP-9. Recombinant human BMP-9-induced ALP activity was suppressed by SB203580, SP600125, and U0126, which are inhibitors of p38, c-Jun N terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2), respectively. Our data suggest that rhBMP-9 is a potent inducer of the differentiation of human PDL fibroblasts into osteoblast-like cells and that this may be mediated by the SMAD and mitogen-activated protein kinase (p38, ERK1/2, and JNK) pathways. PMID- 26879147 TI - [Succession and continuity]. PMID- 26879146 TI - Intrinsic mechanical behavior of femoral cortical bone in young, osteoporotic and bisphosphonate-treated individuals in low- and high energy fracture conditions. AB - Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naive osteoporosis, and bisphosphonate treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates. PMID- 26879148 TI - The impact of orientation filtering on face-selective neurons in monkey inferior temporal cortex. AB - Faces convey complex social signals to primates. These signals are tolerant of some image transformations (e.g. changes in size) but not others (e.g. picture plane rotation). By filtering face stimuli for orientation content, studies of human behavior and brain responses have shown that face processing is tuned to selective orientation ranges. In the present study, for the first time, we recorded the responses of face-selective neurons in monkey inferior temporal (IT) cortex to intact and scrambled faces that were filtered to selectively preserve horizontal or vertical information. Guided by functional maps, we recorded neurons in the lateral middle patch (ML), the lateral anterior patch (AL), and an additional region located outside of the functionally defined face-patches (CONTROL). We found that neurons in ML preferred horizontal-passed faces over their vertical-passed counterparts. Neurons in AL, however, had a preference for vertical-passed faces, while neurons in CONTROL had no systematic preference. Importantly, orientation filtering did not modulate the firing rate of neurons to phase-scrambled face stimuli in any recording region. Together these results suggest that face-selective neurons found in the face-selective patches are differentially tuned to orientation content, with horizontal tuning in area ML and vertical tuning in area AL. PMID- 26879150 TI - Recognition of silver cations by a cucurbit[8]uril-induced supramolecular crown ether. AB - The host-guest interaction of cucurbit[8]uril (Q[8]) with a synthesized guest molecule, consisting of naphthalene and viologen moieties bridged by a carbon oxygen chain, was investigated by (1)H NMR and UV-Vis spectroscopy. The results indicated the formation of an inclusion complex in a ratio of 1 : 1 with a moderate association constant of Ka = (1.1 +/- 0.2) * 10(6) L mol(-1). The formation of this special complex is driven by the markedly enhanced charge transfer interaction between the electron-rich and electron-deficient guest molecule inside the hydrophobic cavity of Q[8], while the carbon oxygen chain stays outside of Q[8] to form a supramolecular crown ether. Screening of the metal cation substrate suggested that the inclusion complex recognizes Ag(+) ions with high selectivity, as shown by UV-Vis spectroscopy. PMID- 26879149 TI - Myeloid Engraftment in Humanized Mice: Impact of Granulocyte-Colony Stimulating Factor Treatment and Transgenic Mouse Strain. AB - Poor myeloid engraftment remains a barrier to experimental use of humanized mice. Focusing primarily on peripheral blood cells, we compared the engraftment profile of NOD-scid-IL2Rgammac(-/-) (NSG) mice with that of NSG mice transgenic for human membrane stem cell factor (hu-mSCF mice), NSG mice transgenic for human interleukin (IL)-3, granulocyte-macrophage-colony stimulating factor (GM-CSF), and stem cell factor (SGM3 mice). hu-mSCF and SGM3 mice showed enhanced engraftment of human leukocytes compared to NSG mice, and this was reflected in the number of human neutrophils and monocytes present in these strains. Importantly, discrete classical, intermediate, and nonclassical monocyte populations were identifiable in the blood of NSG and hu-mSCF mice, while the nonclassical population was absent in the blood of SGM3 mice. Granulocyte-colony stimulating factor (GCSF) treatment increased the number of blood monocytes in NSG and hu-mSCF mice, and neutrophils in NSG and SGM3 mice; however, this effect appeared to be at least partially dependent on the stem cell donor used to engraft the mice. Furthermore, GCSF treatment resulted in a preferential expansion of nonclassical monocytes in both NSG and hu-mSCF mice. Human tubulointerstitial CD11c(+) cells were present in the kidneys of hu-mSCF mice, while monocytes and neutrophils were identified in the liver of all strains. Bone marrow-derived macrophages prepared from NSG mice were most effective at phagocytosing polystyrene beads. In conclusion, hu-mSCF mice provide the best environment for the generation of human myeloid cells, with GCSF treatment further enhancing peripheral blood human monocyte cell numbers in this strain. PMID- 26879151 TI - Mild Cobalt-Catalyzed Negishi Cross-Couplings of (Hetero)arylzinc Reagents with (Hetero)aryl Halides. AB - A catalytic system consisting of CoCl2 ?2 LiCl (5 mol %) and HCO2 Na (50 mol %) enables the cross-coupling of various N-heterocyclic chlorides and bromides as well as aromatic halogenated ketones with various electron-rich and -poor arylzinc reagents. The reactions reached full conversion within a few hours at 25 degrees C. PMID- 26879152 TI - Nocturnally migrating songbirds drift when they can and compensate when they must. AB - The shortest possible migratory route for birds is not always the best route to travel. Substantial research effort has established that birds in captivity are capable of orienting toward the direction of an intended goal, but efforts to examine how free-living birds use navigational information under conditions that potentially make direct flight toward that goal inefficient have been limited in spatiotemporal scales and in the number of individuals observed because of logistical and technological limitations. Using novel and recently developed techniques for analysis of Doppler polarimetric weather surveillance radar data, we examined two impediments for nocturnally migrating songbirds in eastern North America following shortest-distance routes: crosswinds and oceans. We found that migrants in flight often drifted sideways on crosswinds, but most strongly compensated for drift when near the Atlantic coast. Coastal migrants' tendency to compensate for wind drift also increased through the night, while no strong temporal differences were observed at inland sites. Such behaviors suggest that birds migrate in an adaptive way to conserve energy by assessing while airborne the degree to which they must compensate for wind drift. PMID- 26879153 TI - Automaticity of Conceptual Magnitude. AB - What is bigger, an elephant or a mouse? This question can be answered without seeing the two animals, since these objects elicit conceptual magnitude. How is an object's conceptual magnitude processed? It was suggested that conceptual magnitude is automatically processed; namely, irrelevant conceptual magnitude can affect performance when comparing physical magnitudes. The current study further examined this question and aimed to expand the understanding of automaticity of conceptual magnitude. Two different objects were presented and participants were asked to decide which object was larger on the screen (physical magnitude) or in the real world (conceptual magnitude), in separate blocks. By creating congruent (the conceptually larger object was physically larger) and incongruent (the conceptually larger object was physically smaller) pairs of stimuli it was possible to examine the automatic processing of each magnitude. A significant congruity effect was found for both magnitudes. Furthermore, quartile analysis revealed that the congruity was affected similarly by processing time for both magnitudes. These results suggest that the processing of conceptual and physical magnitudes is automatic to the same extent. The results support recent theories suggested that different types of magnitude processing and representation share the same core system. PMID- 26879154 TI - Dynamic Mechanical Allodynia--One Clinical Sign, Several Mechanisms: Five Illustrative Cases. AB - Pain evoked by tangential movement across the skin is usually defined as dynamic mechanical allodynia (DMA). Some patients complain of DMA as troublesome as spontaneous pain and refer a marked interfering with activities of daily living and sleep. Pathophysiology of DMA is complex and can be related to several mechanisms, both nociceptive and neuropathic. Five exemplificative clinical cases of DMA are presented, each associated to a possible specific mechanism: injured skin DMA, peri-injured skin DMA, far injury DMA, nerve-confined DMA and fear DMA (pseudo allodynia). The identification of these subcategories of DMA can stimulate further studies aimed at evaluating the usefulness of a mechanism-based therapy for the different clinical forms of DMA. PMID- 26879156 TI - The Genetic History of Peruvian Quechua-Lamistas and Chankas: Uniparental DNA Patterns among Autochthonous Amazonian and Andean Populations. AB - This study focuses on the genetic history of the Quechua-Lamistas, inhabitants of the Lamas Province in the San Martin Department, Peru, who speak their own distinct variety of the Quechua family of languages. It has been suggested that different pre-Columbian ethnic groups from the Peruvian Amazonia, like the Motilones or "shaven heads", assimilated the Quechua language and then formed the current native population of Lamas. However, many Quechua-Lamistas claim to be direct descendants of the Chankas, a famous pre-Columbian indigenous group that escaped from Inca rule in the Andes. To investigate the Quechua-Lamistas and Chankas' ancestries, we compared uniparental genetic profiles (17 STRs of Q-M3 Y chromosome and mtDNA complete control region haplotypes) among autochthonous Amazonian and Andean populations from Peru, Bolivia and Ecuador. The phylogeographic and population genetic analyses indicate a fairly heterogeneous ancestry for the Quechua-Lamistas, while they are closely related to their neighbours who speak Amazonian languages, presenting no direct relationships with populations from the region where the ancient Chankas lived. On the other hand, the genetic profiles of self-identified Chanka descendants living in Andahuaylas (located in the Apurimac Department, Peru, in the Central Andes) were closely related to those living in Huancavelica and the assumed Chanka Confederation area before the Inca expansion. PMID- 26879157 TI - A common 'aggregation-prone' interface possibly participates in the self-assembly of human zona pellucida proteins. AB - Human zona pellucida (ZP) is composed of four glycoproteins, namely ZP1, ZP2, ZP3 and ZP4. ZP proteins form heterodimers, which are incorporated into filaments through a common bipartite polymerizing component, designated as the ZP domain. The latter is composed of two individually folded subdomains, named ZP-N and ZP C. Here, we have synthesized six 'aggregation-prone' peptides, corresponding to a common interface of human ZP2, ZP3 and ZP4. Experimental results utilizing electron microscopy, X-ray diffraction, ATR FT-IR spectroscopy and polarizing microscopy indicate that these peptides self-assemble forming fibrils with distinct amyloid-like features. Finally, by performing detailed modeling and docking, we attempt to shed some light in the self-assembly mechanism of human ZP proteins. PMID- 26879158 TI - Pro- and anticoagulant factors facilitate thrombin generation and balance the haemostatic response to FEIBA((r)) in prophylactic therapy. AB - INTRODUCTION: FEIBA((r)) consists of zymogens and traces of activated forms of procoagulant factors II, VII, IX, X, anticoagulants protein C and TFPI, and small amounts of cofactors FV, FVIII and protein S, in a balanced ratio. As shown previously, FII-FXa complex plays a key role in FEIBA's mode of action (MoA). METHODS: Thrombin generation (TG) was measured by spiking coagulation factors, cofactors and inhibitors to high titer FVIII inhibitor plasma, and in plasma samples from patients in a phase 3 clinical study evaluating the safety and efficacy of FEIBA prophylaxis in haemophilia A patients with inhibitors. RESULTS: Increasing the FXa/FII ratio improved TG, while adding coagulation enzyme components had a negligible effect. Adding FX, FIX, and FVII increased the peak thrombin and decreased the lag time. The presence of FV and phospholipids led to faster TG, while protein C and protein S reduced the amount of peak thrombin. TFPI appeared to have no effect. Patients on prophylaxis with FEIBA((r)) showed higher peak thrombin and AUC with elevated FII, FX, FIX, FVIIa, and protein C levels, and experienced significantly less bleeding episodes than those receiving on-demand treatment. CONCLUSION: These experiments showed that although the FII FXa complex induced immediate thrombin formation on the activated platelet surface, other procoagulant components of FEIBA were necessary to achieve an optimal thrombin burst. The presence of the pro- and anti-coagulants in FEIBA provides a haemostatic balance, and is thus expected to prevent thrombotic events. Recent clinical data verified the postulated MoA of FEIBA in prophylaxis treatment. PMID- 26879159 TI - Endoscopic ultrasound pin-points the precision medicine for pancreatic cancer. PMID- 26879160 TI - Credentialing for endoscopic ultrasound: A proposal for Canadian guidelines. PMID- 26879162 TI - Endoscopic ultrasound-guided fine needle aspiration: The wet suction technique. AB - Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a fundamental tool in obtaining cytopathological diagnosis of pancreatic tumors. When sampling solid lesions of the pancreas, the endosonographer can use two suction techniques to enhance tissue acquisition; the dry and the wet suction techniques. The standard dry suction technique relies on applying negative pressure suction on the proximal end of the needle after the stylet is removed with a pre-vacuum syringe. The wet suction technique relies on pre-flushing the needle with saline to replace the column of air with fluid followed by aspiration the proximal end by using a prefilled syringe with saline. A new modified wet suction technique (hybrid suction technique) relies on preloading the needle with saline, but having continuous negative pressure with a pre-vacuum syringe to avoid manual intermittent suction. Tissue acquisition can be enhanced by applying fluid dynamic principles to the current aspiration techniques, such as the column of water used in the needle of the wet technique. In this review, we will focus on EUS-FNA using the wet suction technique for sampling of pancreatic solid lesions. PMID- 26879161 TI - The role of endoscopic ultrasound in pancreatic cancer screening. AB - Pancreatic cancer (PC) is a highly lethal cancer. Despite a significant advancement in cancer treatment, the mortality rate of PC is nearly identical to the incidence rates. Early detection of tumor or its precursor lesions with dysplasia may be the most effective approach to improve survival. Screening strategies should include identification of the population at high risk of developing PC, and an intense application of screening tools with adequate sensitivity to detect PC at an early curable stage. Endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI) seem to be the most promising modalities for PC screening based on the data so far. EUS had an additional advantage over MRI by being able to obtain tissue sample during the same examination. Several questions remain unanswered at this time regarding the age to begin screening, frequency of screening, management of asymptomatic pancreatic lesions detected on screening, timing of resection, and extent of surgery and impact of screening on survival. Novel techniques such as needle-based confocal laser endomicroscopy (nCLE), along with biomarkers, may be helpful to identify pancreatic lesions with more aggressive malignant potential. Further studies will hopefully lead to the development of strategies combining EUS with other technological/biological advancements that will be cost-effective and have an impact on survival. PMID- 26879163 TI - Imaging of pancreas divisum by linear-array endoscopic ultrasonography. AB - Pancreas divisum (PD) is the most common developmental anatomic variant of pancreatic duct. Endoscopic ultrasound (EUS) is often performed to evaluate idiopathic pancreatitis and has been shown to have high accuracy in diagnosis of PD. The different techniques to identify PD by linear EUS have been described differently by different authors. If EUS is done with a proper technique it can be a valuable tool in the diagnosis of PD. The anatomical and technical background of different signs has not been described so far. This article summarizes the different techniques of imaging of pancreatic duct in a suspected case of PD and gives a technical explanation of various signs. The common signs seen during evaluation of pancreatic duct in PD are stack sign of linear EUS, crossed duct sign on linear EUS, the dominant duct and ventral dorsal duct (VD) transition. Few other signs are described which include duct above duct, short ventral duct /absent ventral duct, separate opening of ducts with no communication, separate opening of ducts with filamentous communication, stacking of duct of Santorini and indirect signs like santorinecele. The principles of the sign have been explained on an anatomical basis and the techniques and the principles described in the review will be helpful in technical evaluation of PD during EUS. PMID- 26879164 TI - Diagnostic potency of EUS-guided FNA for the evaluation of pancreatic mass lesions. AB - BACKGROUND AND OBJECTIVES: Diagnosis of pancreatic lesions remains a clinical challenge. This study aimed to evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic mass lesions. PATIENTS AND METHODS: Clinical data, laboratory tests, and cytopathological and imaging reports were collected from 185 pancreatic EUS cases performed from March 2010 to January 2014. The final diagnosis was based on surgical findings, EUS-FNA or computed tomography (CT)-guided biopsy. RESULTS: A total of 100 pancreatic FNAs were obtained by EUS. Most positive diagnoses of malignancy were pancreatic adenocarcinomas (n = 61). The site of pancreatic adenocarcinoma was the head in 50 (82.0%), body in seven (11.5%), and tail in four (6.5%). The sensitivity, specifi city, and positive and negative predictive values of EUS-FNA for diagnosing adenocarcinoma were 80.3%, 92.3%, 94.2%, and 75.0%, respectively. DISCUSSION: We concluded that EUS-FNA of pancreatic lesion accurately diagnoses pancreatic adenocarcinoma and should be considered for the standard management of pancreatic adenocarcinoma. PMID- 26879165 TI - A novel fusion imaging system for endoscopic ultrasound. AB - BACKGROUND AND OBJECTIVE: Navigation of a flexible endoscopic ultrasound (EUS) probe inside the gastrointestinal (GI) tract is problematic due to the small window size and complex anatomy. The goal of the present study was to test the feasibility of a novel fusion imaging (FI) system which uses electromagnetic (EM) sensors to co-register the live EUS images with the pre-procedure computed tomography (CT) data with a novel navigation algorithm and catheter. METHODS: An experienced gastroenterologist and a novice EUS operator tested the FI system on a GI tract bench top model. Also, the experienced gastroenterologist performed a case series of 20 patients during routine EUS examinations. RESULTS: On the bench top model, the experienced and novice doctors reached the targets in 67 +/- 18 s and 150 +/- 24 s with a registration error of 6 +/- 3 mm and 11 +/- 4 mm, respectively. In the case series, the total procedure time was 24.6 +/- 6.6 min, while the time to reach the clinical target was 8.7 +/- 4.2 min. CONCLUSIONS: The FI system is feasible for clinical use, and can reduce the learning curve for EUS procedures and improve navigation and targeting in difficult anatomic locations. PMID- 26879166 TI - The utility of endobronchial ultrasound-transbronchial needle aspiration in lymphoma. AB - BACKGROUND AND OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has a well established role in the diagnosis and staging of lung cancer. This technology is also widely used for the diagnosis of mediastinal masses and cysts as well as other inflammatory disorders such as sarcoidosis. However, the utility of this procedure in the diagnosis and subclassification of lymphoproliferative disorders (LPDs) is not clear. We performed a systematic review to evaluate EBUS-TBNA use in LPDs. MATERIALS AND METHODS: PubMed, EMBASE, MEDLINE, Cochrane Library Plus, and ISI Web of Knowledge were searched for studies of clinical trials in English reporting diagnostic performance of EBUS-TBNA in lymphoma until September 2014. The overall sensitivity, negative predictive value (NPV), and diagnostic accuracy were evaluated. RESULTS: Six trials involving 346 patients with suspected lymphoma were included. The overall sensitivity, NPV, and diagnostic accuracy ranged 38%-91%, 83%-96.4%, and 91%-97%, respectively. Further invasive surgery was needed only in 13-43% of the patients. None of the studies included in the present review reported important complications. CONCLUSION: Current evidence suggests that EBUS-TBNA can be used as an initial evaluation for patients with suspected lymphoma. Additional surgical procedures may be necessary if a sample is inadequate or negative with high suspicion of lymphoma. Further multicenter trials are needed to evaluate the diagnostic yield of EBUS-TBNA in lymphoma patients. PMID- 26879167 TI - Risk factors for aggressive nonfunctional pancreatic neuroendocrine tumors and the role of endoscopic ultrasound guided fine-needle aspiration. AB - BACKGROUND: Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are increasingly being diagnosed but management, especially of small tumors, remains a clinical dilemma. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is now routinely used for diagnosis of pancreatic neuroendocrine tumors (pNETs) but has not been well studied as a tool for identifying aggressive disease. MATERIALS AND METHODS: A systematic search of the cytology database identified all patients at our center who underwent EUS-FNA from 1999 through 2011 and were diagnosed with NF-pNET. RESULTS: A total of 50 patients were identified. Though patients with metastatic disease had a mean tumor size of 40 mm compared to 25 mm in patients without metastatic disease (P = 0.04), we also identified several patients with tumors <20 mm who presented with metastatic disease. Furthermore, we found no statistically significant difference in metastatic disease between tumors <20 mm and >20 mm (P = 0.13). Using receiver operating characteristic (ROC) analysis, we found that using a cutoff point of 20 mm only led to a sensitivity of 85% in screening for metastases, while lowering the cutoff point to 18 mm allowed for a sensitivity of 95%. CONCLUSION: Currently, guidelines suggest that only patients with tumors greater than 20 mm undergo surgical resection, as tumors less than this size are thought to have low risk of metastases. Our analysis suggests that these recommendations could lead to undertreating patients with small tumors. Tumor size alone may be inadequate as a marker for aggressive NF-pNETs. Given this, other risk factors for aggressive pNETs should be studied to help identify the patients most likely to benefit from surgery. PMID- 26879168 TI - Sudden appearance of free fluid during endoscopic ultrasound-guided fine-needle aspiration. AB - During endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of a pancreatic malignancy, a small quantity of free fluid, not seen before, suddenly appeared in the view, and time was spent ruling out ongoing hemorrhage. However, during follow-up, the patient gradually developed peritoneal signs and was referred for surgery. The images presented elucidate the diagnosis and raise the question of a theoretical change in diagnostic and therapeutic approach. PMID- 26879169 TI - Pulmonary aspergillosis diagnosed by endoscopic ultrasound fine-needle aspiration. AB - Pulmonary aspergillosis generally occurs in patients with prolonged neutropenia or immunosupression. Definitive diagnosis depends on the demonstration of the organism in tissue, as positive culture result from sputum, needle biopsy, or bronchoalveolar lavage fluid. Even though endoscopic ultrasound (EUS) fine needle aspiration (FNA) of paraesophageal/mediastinal lesions has been used numerous times, this is the first case that reports an aspergilloma diagnosed by EUS-FNA, allowing us to reach a definitive diagnosis. We present a patient with a nodular lesion located in the right upper lobe lung, with ground-glass opacity. Upper EUS revealed an ill-defined hypoechoic paraesophageal lesion with a central annular image. Culture results from EUS-FNA were positive for Aspergillus fumigatus. There are no previous reports of EUS imaging features of pulmonary aspergillosis. We believe that this central annular image in an ill-defined hypoechoic paraesophageal lesion may be a characteristic feature. PMID- 26879170 TI - Primary esophageal tuberculosis mimicking esophageal cancer with vascular involvement. PMID- 26879171 TI - Endoscopic ultrasound elastography in the diagnosis of incidental malignant mesothelioma. PMID- 26879173 TI - Corrigendum to "Linezolid for Treating Tuberculosis: A Delicate Balancing Act" [EBioMedicine 2 (11) (November 2015) 1568-1569]. PMID- 26879172 TI - Upregulation of inducible NO synthase by exogenous adenosine in vascular smooth muscle cells activated by inflammatory stimuli in experimental diabetes. AB - BACKGROUND: Adenosine has been shown to induce nitric oxide (NO) production via inducible NO synthase (iNOS) activation in vascular smooth muscle cells (VSMCs). Although this is interpreted as a beneficial vasodilating pathway in vaso occlusive disorders, iNOS is also involved in diabetic vascular dysfunction. Because the turnover of and the potential to modulate iNOS by adenosine in experimental diabetes have not been explored, we hypothesized that both the adenosine system and control of iNOS function are impaired in VSMCs from streptozotocin-diabetic rats. METHODS: Male Sprague-Dawley rats were injected with streptozotocin once to induce diabetes. Aortic VSMCs from diabetic and nondiabetic rats were isolated, cultured and exposed to lipopolysaccharide (LPS) plus a cytokine mix for 24 h in the presence or absence of (1) exogenous adenosine and related compounds, and/or (2) pharmacological agents affecting adenosine turnover. iNOS functional expression was determined by immunoblotting and NO metabolite assays. Concentrations of adenosine, related compounds and metabolites thereof were assayed by HPLC. Vasomotor responses to adenosine were determined in endothelium-deprived aortic rings. RESULTS: Treatment with adenosine-degrading enzymes or receptor antagonists increased iNOS formation in activated VSMCs from nondiabetic and diabetic rats. Following treatment with the adenosine transport inhibitor NBTI, iNOS levels increased in nondiabetic but decreased in diabetic VSMCs. The amount of secreted NO metabolites was uncoupled from iNOS levels in diabetic VSMCs. Addition of high concentrations of adenosine and its precursors or analogues enhanced iNOS formation solely in diabetic VSMCs. Exogenous adenosine and AMP were completely removed from the culture medium and converted into metabolites. A tendency towards elevated inosine generation was observed in diabetic VSMCs, which were also less sensitive to CD73 inhibition, but inosine supplementation did not affect iNOS levels. Pharmacological inhibition of NOS abolished adenosine-induced vasorelaxation in aortic tissues from diabetic but not nondiabetic animals. CONCLUSIONS: Endogenous adenosine prevented cytokine- and LPS-induced iNOS activation in VSMCs. By contrast, supplementation with adenosine and its precursors or analogues enhanced iNOS levels in diabetic VSMCs. This effect was associated with alterations in exogenous adenosine turnover. Thus, overactivation of the adenosine system may foster iNOS-mediated diabetic vascular dysfunction. PMID- 26879174 TI - An ERp57-mediated disulphide exchange promotes the interaction between Burkholderia cenocepacia and epithelial respiratory cells. AB - Previous studies have demonstrated that extracellular glutathione reduces the ability of the Cystic Fibrosis pathogen Burkholderia cenocepacia to infect primary or immortalized epithelial respiratory cells. We report here that the adhesion and invasion ability of B. cenocepacia is limited also by thiol oxidizing and disulphide-reducing agents and by protein disulfide isomerase (PDI) inhibitors. PDI inhibitors also reduce the proinflammatory response elicited by cells in response to Burkholderia. These findings indicate that a membrane associated PDI catalyzes thiol/disulphide exchange reactions which favor bacterial infection. The combined use of selective PDI inhibitors, RNA silencing and specific antibodies identified ERp57 as a major PDI involved in the interaction between B. cenocepacia and epithelial cells. This study contributes to the elucidation of the Burkholderia pathogenic mechanisms by showing that this microorganism exploits a membrane-associated host protein to infect epithelial cells and identifies ERp57 as a putative pharmacological target for the treatment of Burkholderia lung infections. PMID- 26879175 TI - Reproducibility of the items on the Stroke Specific Quality of Life questionnaire that evaluate the participation component of the International Classification of Functioning, Disability and Health. AB - PURPOSE: To evaluate the reproducibility of the Stroke Specific Quality of Life (SS-QOL) items that address the participation component of the International Classification of Functioning, Disability and Health (ICF) and analyse the correlation between the subscore of these 26 items and the total SS-QOL score. METHODS: Seventy-five stroke survivors participated in this study. Reproducibility was evaluated using the intraclass correlation coefficient (ICC2,1), standard error of measurement (SEM), minimum detectable change (MDC) and the Bland-Altman plot. The correlation between the subscore of the 26 items and the total SS-QOL score was analysed using Spearman's correlation coefficients (rho) and simple linear regression. An alpha risk <= 0.05 was considered for all analyses. RESULTS: The SS-QOL items that address the participation component of the ICF demonstrated excellent reliability (intra-rater ICC2,1 = 0.96; inter rater ICC2,1 = 0.95). The SEM and MDC were adequate. The Bland-Altman plot demonstrated satisfactory agreement. A significant and strong correlation (rho = 0.83) was found between the 26 SS-QOL items that address participation and the total SS-QOL score. Moreover, the evaluation of participation was found to explain 73% of the evaluation of health-related quality of life. CONCLUSION: The 26 SS-QOL items that address the participation component of the ICF demonstrated adequate reproducibility. Thus, participation, which represents the social aspects of functionality, can be adequately evaluated with these items. Implications for Rehabilitation The 26 Stroke Specific Quality of Life items that address participation proved to be reproducible for the analysis of social participation following a stroke. The findings can lead to a better understanding of the social participation of individuals with chronic hemiparesis and assist in the establishment of adequate treatment for such individuals. The rehabilitation process can be directed towards more specific goals focused on the patient expectations, thereby contributing to greater humanization and effectiveness of treatment to improve social participation following a stroke. PMID- 26879176 TI - Global burden of cutaneous leishmaniasis: a cross-sectional analysis from the Global Burden of Disease Study 2013. AB - BACKGROUND: High-quality epidemiological studies evaluating the burden of cutaneous leishmaniasis worldwide are lacking. We compared the burden of cutaneous leishmaniasis in each country to the overall global burden and assessed the equality of cutaneous leishmaniasis burden across different countries and regions. METHODS: Data were extracted from scientific literature, hospital sources, country reports, and WHO sources on the prevalence of sequalae of both acute and chronic cutaneous leishmaniasis. Prevalence data were combined with a disability weight to yield years lived with disability. Disability-adjusted life years (DALYs) are a sum of the years lived with disability and years of life lost (or mortality, assumed to be zero). We compared DALYs due to cutaneous leishmaniasis for 152 countries using standard Z score analysis with Bonferroni correction (p<0.003) and generation of Lorenz curves with a Gini coefficient. FINDINGS: In 2013, the global mean age-standardised DALYs for cutaneous leishmaniasis was 0.58 per 100 000 people. Nine countries had significantly greater DALYs from cutaneous leishmaniasis than the mean: Afghanistan (87.0), Sudan (20.2), Syria (9.2), Yemen (6.2), Iraq (6.0), Burkina Faso (4.8), Bolivia (4.6), Haiti (4.1), and Peru (4.0). The Gini coefficient was 0.89. Andean Latin America, North Africa and Middle East, western sub-Saharan Africa, and south Asia had the highest DALYs from cutaneous leishmaniasis. Among males, Palestine had the highest incidence rates (616.2 cases per 100 000 people) followed by Afghanistan (566.4), Syria (357.1), and Nicaragua (354.8). Among females, Afghanistan had the highest incidence rates (623.9) followed by Syria (406.3), Palestine (222.1), and Nicaragua (180.8). Similar proportions of males and females had cutaneous leishmaniasis in most countries with a high incidence. INTERPRETATION: The burden from cutaneous leishmaniasis mainly falls on countries in Africa and the Middle East. Global and national data on the burden of cutaneous leishmaniasis disease are pivotal to promote field studies and initiate behavioural change. FUNDING: Bill & Melinda Gates Foundation. PMID- 26879177 TI - Estimations of cutaneous leishmaniasis burden: a constant challenge. PMID- 26879178 TI - No outgrowth of chondrocytes from non-digested particulated articular cartilage embedded in commercially available fibrin matrix: an in vitro study. AB - BACKGROUND: Commercially available fibrin is routinely being used as both a matrix in certain cartilage repair techniques and a method for scaffold fixation. Chondrocytes from non-digested particulated cartilage fragments are proposed as a possible source for new cartilage tissue formation in some operative techniques. The goal of this study was to test that chondrocytes from particulated articular cartilage embedded in fibrin have an active role in the process of cartilage repair, as well as if commercially available fibrin should be used as a suitable matrix. METHODS: Articular cartilage was obtained from patients undergoing total knee replacement surgery. The biopsies were particulated in small, 1-2-mm(3) pieces and embedded in fibrin. Two groups were compared in our study, particulated articular cartilage with and without collagenase treatment. The specimens were analyzed by optical microscopy after 2-5 weeks of cultivation in a special construct embedded in a cell culture medium containing particulated cartilage embedded in fibrin in the upper phase and cancellous bone in the lower phase under the perforated nylon membrane. RESULTS: None of the biopsies taken from four different patients showed the outgrowth of chondrocytes or bone marrow originated cells into the fibrin matrix in our experimental model. CONCLUSIONS: It has been shown in our experimental model in vitro little to support the theory that articular chondrocytes from particulated articular cartilage embedded in fibrin have an active role in cartilage repair in its early stage. PMID- 26879180 TI - Associations of Plasma FGF2 Levels and Polymorphisms in the FGF2 Gene with Obesity Phenotypes in Han Chinese Population. AB - Obesity is highly heritable, but the specific genes influencing obesity related traits are largely unknown. Fibroblast growth factor 2 (FGF2) could influence adipocyte differentiation. However, the association of FGF2 polymorphisms and obesity remains unclear. This study aimed to investigate the associations of both the plasma FGF2 levels and SNPs in FGF2 gene with obesity phenotypes in Han Chinese populations. Plasma FGF2 levels were measured and subjected to association analyses in 62 subjects. Eleven SNPs in FGF2 were genotyped and tested for associations in a discovery sample of 1,300 subjects. SNPs significantly associated with obesity were subjected to replication in another independent sample of 1,035 subjects. We found that plasma FGF2 levels were positively correlated with fat mass (P = 0.010). Association analyses in the discovery sample identified three SNPs (rs1449683, rs167428, rs308442) significantly associated with fat mass after multiple testing adjustments (P < 0.0045). Subsequent replication study successfully validated one SNP (rs167428) associated with fat mass (P(combine) = 3.46 * 10(-5)). eQTL analyses revealed that SNPs associated with obesity also affected FGF2 expression. Our findings suggested that high plasma FGF2 level correlated with increased risk of obesity, and FGF2 gene polymorphisms could affect individual variances of obesity in Han Chinese population. PMID- 26879179 TI - Spatial patterns of arrests, police assault and addiction treatment center locations in Tijuana, Mexico. AB - AIMS: In the context of a public health-oriented drug policy reform in Mexico, we assessed the spatial distribution of police encounters among people who inject drugs (PWID) in Tijuana, determined the association between these encounters and the location of addiction treatment centers and explored the association between police encounters and treatment access. DESIGN: Geographically weighted regression (GWR) and logistic regression analysis using prospective spatial data from a community-recruited cohort of PWID in Tijuana and official geographical arrest data from the Tijuana Municipal Police Department. SETTING: Tijuana, Mexico. PARTICIPANTS: A total of 608 participants (median age 37; 28.4% female) in the prospective Proyecto El Cuete cohort study recruited between January and December 2011. MEASUREMENTS: We compared the mean distance of police encounters and a randomly distributed set of events to treatment centers. GWR was undertaken to model the spatial relationship between police interactions and treatment centers. Logistic regression analysis was used to investigate factors associated with reporting police interactions. FINDINGS: During the study period, 27.5% of police encounters occurred within 500 m of treatment centers. The GWR model suggested spatial correlation between encounters and treatment centers (global R(2) = 0.53). Reporting a need for addiction treatment was associated with reporting arrest and police assault [adjusted odds ratio = 2.74, 95% confidence interval (CI) = 1.25-6.02, P = 0.012]. CONCLUSIONS: A geospatial analysis suggests that, in Mexico, people who inject drugs are at greater risk of being a victim of police violence if they consider themselves in need of addiction treatment, and their interactions with police appear to be more frequent around treatment centers. PMID- 26879181 TI - Acupuncture for fibromyalgia in primary care: a randomised controlled trial. AB - OBJECTIVES: To evaluate the efficacy of an individualised acupuncture protocol for patients with fibromyalgia. METHODS: Randomised controlled multicentre trial, blinded to participants and to data analysts. Conducted in three primary care centres in southern Spain. A total of 164 participants aged over 17 years and diagnosed with fibromyalgia were enrolled in this trial; 153 participants completed the study. Participants were randomly assigned to either the real intervention (individualised acupuncture, IA) or the sham intervention (sham acupuncture, SA). In both the IA and SA groups, one session per week (lasting 20 min) was provided, in addition to usual pharmacological treatment. The primary outcome was change in pain intensity at 10 weeks. RESULTS: Intention-to-treat analysis revealed that the decrease in pain intensity at 10 weeks was greater (p=0.001) in the IA group (-41.0%, 95% CI -47.2% to -34.8%) than in the SA group (-27.1%, 95% CI -33.2% to -20.9%). During the follow-up period, significant differences (p<0.01) in favour of the IA group persisted at 12 months (IA: 19.9%, 95% CI -24.6% to -15.1%; vs SA: -6.2%, 95% CI -11.2% to -1.2%). CONCLUSIONS: Individualised acupuncture treatment in primary care in patients with fibromyalgia proved efficacious in terms of pain relief, compared with placebo treatment. The effect persisted at 1 year, and its side effects were mild and infrequent. Therefore, the use of individualised acupuncture in patients with fibromyalgia is recommended. TRIAL REGISTRATION NUMBER: ISRCTN60217348. PMID- 26879182 TI - 15 Hz electroacupuncture at ST36 improves insulin sensitivity and reduces free fatty acid levels in rats with chronic dexamethasone-induced insulin resistance. AB - OBJECTIVE: To evaluate the effect of electroacupuncture (EA) in a rat model of chronic steroid-induced insulin resistance (SIIR). METHODS: An SIIR rat model was created using daily intraperitoneal injections of clinically relevant doses of dexamethasone (1 mg/kg) for 5 days to induce chronic insulin resistance. Thirty six SIIR rats were randomly divided into the SIIR+EA group (n=18), which received 15 Hz EA at ST36 for 60 min, and the SIIR group (n=18), which remained untreated. Plasma glucose and free fatty acid (FFA) levels were measured in serial blood samples taken without further manipulation (n=6 per group) and during insulin challenge test (ICT, n=6 per group) and intravenous glucose tolerance test (ivGTT, n=6 per group). Insulin receptor substrate (IRS)-1 and glucose transporter (GLUT)-4 were measured using Western blotting and expressed relative to beta-actin. RESULTS: Following EA, area-under-the-curve (AUC) for glucose was reduced (7340+/-291 vs 10 705+/-1474 mg/dL/min, p=0.049) and FFA levels significantly lower at 30/60 min in the SIIR+EA versus SIIR groups. Similar effects on glucose AUC were seen during the ICT (5568+/-275 vs 7136+/-594 mg/dL/min, p<0.05) and igVTT (11 498+/-1398 vs 16 652+/-1217 mg/dL/min, p<0.01). FFA levels were lower at 30 and/or 60 min in SIIR+EA versus SIIR groups (p<0.01). Relative expression of IRS-1 and GLUT4 were significantly increased by EA (p<0.01). CONCLUSIONS: EA decreased the FFA level and increased insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA is an effective alternative treatment for the reduction of insulin resistance in patients requiring chronic use of dexamethasone. PMID- 26879183 TI - Training and transfer effects of N-back training for brain-injured and healthy subjects. AB - Working memory impairments are prevalent among patients with acquired brain injury (ABI). Computerised training targeting working memory has been researched extensively using samples from healthy populations but this field remains isolated from similar research in ABI patients. We report the results of an actively controlled randomised controlled trial in which 17 patients and 18 healthy subjects completed training on an N-back task. The healthy group had superior improvements on both training tasks (SMD = 6.1 and 3.3) whereas the ABI group improved much less (SMD = 0.5 and 1.1). Neither group demonstrated transfer to untrained tasks. We conclude that computerised training facilitates improvement of specific skills rather than high-level cognition in healthy and ABI subjects alike. The acquisition of these specific skills seems to be impaired by brain injury. The most effective use of computer-based cognitive training may be to make the task resemble the targeted behaviour(s) closely in order to exploit the stimulus-specificity of learning. PMID- 26879186 TI - Specific Antivirulence Activity, A New Concept for Reliable Screening of Virulence Inhibitors. AB - Antivirulence therapy, disarming pathogens rather than killing them, is emerging as a novel strategy for disease control. Reporter strains expressing an easily measurable and quantifiable phenotype enable easy screening of virulence inhibitors. In this paper I propose a novel concept to exclude false positives in this type of screening. PMID- 26879184 TI - The Impact of Sex Work Interruption on Blood-Derived T Cells in Sex Workers from Nairobi, Kenya. AB - BACKGROUND: Unprotected sexual intercourse exposes the female genital tract (FGT) to semen-derived antigens, which leads to a proinflammatory response. Studies have shown that this postcoital inflammatory response can lead to recruitment of activated T cells to the FGT, thereby increasing risk of HIV infection. OBJECTIVE: The purpose of this study was to evaluate the impact of sex work on activation and memory phenotypes of peripheral T cells among female sex workers (FSW) from Nairobi, Kenya. SUBJECTS: Thirty FSW were recruited from the Pumwani Sex Workers Cohort, 10 in each of the following groups: HIV-exposed seronegative (at least 7 years in active sex work), HIV positive, and New Negative (HIV negative, less than 3 years in active sex work). Blood was obtained at three different phases (active sex work, abstinence from sex work-sex break, and following resumption of sex work). Peripheral blood mononuclear cells were isolated and stained for phenotypic markers (CD3, CD4, CD8, and CD161), memory phenotype markers (CD45RA and CCR7), activation markers (CD69, HLA-DR, and CD95), and the HIV coreceptor (CCR5). T-cell populations were compared between groups. RESULTS: In HIV-positive women, CD8+CCR5+ T cells declined at the sex break period, while CD4+CD161+ T cells increased when returning to sex work. All groups showed no significant changes in systemic T-cell activation markers following the interruption of sex work, however, significant reductions in naive CD8+ T cells were noted. For each of the study points, HIV positives had higher effector memory and CD8+CD95+ T cells and lower naive CD8+ T cells than the HIV-uninfected groups. CONCLUSIONS: Interruption of sex work had subtle effects on systemic T cell memory phenotypes. PMID- 26879185 TI - Identifying small groups of foods that can predict achievement of key dietary recommendations: data mining of the UK National Diet and Nutrition Survey, 2008 12. AB - OBJECTIVE: Many dietary assessment methods attempt to estimate total food and nutrient intake. If the intention is simply to determine whether participants achieve dietary recommendations, this leads to much redundant data. We used data mining techniques to explore the number of foods that intake information was required on to accurately predict achievement, or not, of key dietary recommendations. DESIGN: We built decision trees for achievement of recommendations for fruit and vegetables, sodium, fat, saturated fat and free sugars using data from a national dietary surveillance data set. Decision trees describe complex relationships between potential predictor variables (age, sex and all foods listed in the database) and outcome variables (achievement of each of the recommendations). SETTING: UK National Diet and Nutrition Survey (NDNS, 2008-12). SUBJECTS: The analysis included 4156 individuals. RESULTS: Information on consumption of 113 out of 3911 (3 %) foods, plus age and sex was required to accurately categorize individuals according to all five recommendations. The best trade-off between decision tree accuracy and number of foods included occurred at between eleven (for fruit and vegetables) and thirty-two (for fat, plus age) foods, achieving an accuracy of 72 % (for fat) to 83 % (for fruit and vegetables), with similar values for sensitivity and specificity. CONCLUSIONS: Using information on intake of 113 foods, it is possible to predict with 72-83 % accuracy whether individuals achieve key dietary recommendations. Substantial further research is required to make use of these findings for dietary assessment. PMID- 26879187 TI - Graphene in Regenerative Medicine: Focus on Stem Cells and Neuronal Differentiation. AB - Emerging graphene-based materials offer numerous opportunities to design novel scaffolds for neural tissue engineering. Graphene is a promising candidate due to its superior topographical, chemical, and electrical cues compared with conventional biomaterials. Here we examine the state of the art in graphene-based materials science for the neurodifferentiation of stem cells. PMID- 26879188 TI - Quality by Design (QbD)-Based Process Development for Purification of a Biotherapeutic. AB - Quality by Design (QbD) is currently receiving increased attention from the pharmaceutical community. As a result, most major biotech manufacturers are in varying stages of implementing QbD. Here, I present a case study that illustrates the step-by-step development using QbD of a purification process for the production of a biosimilar product: granulocyte colony-stimulating factor (GCSF). I also highlight and discuss the advantages that QbD-based process development offers over traditional approaches. The case study is intended to help those who wish to implement QbD towards the development and commercialization of biotech products. PMID- 26879189 TI - Ultraviolet/visible photodetectors with ultrafast, high photosensitivity based on 1D ZnS/CdS heterostructures. AB - One-dimensional (1D) semiconducting heterostructures have been widely studied for optoelectronics applications because of their unique geometry and attractive physical properties. In this study, we successfully synthesized 1D ZnS/CdS heterostructures, which can be used to fabricate high performance ultraviolet/visible photodetectors. Due to the separation of photo-generated electron-hole pairs, the resultant photodetector showed excellent photoresponse properties, including ultrahigh Ion/Ioff ratios (up to 10(5)) and specific detectivity (2.23 * 10(14) Jones), relatively fast response speed (5 ms), good stability and reproducibility. Moreover, the as-fabricated flexible photodetectors showed great mechanical stability under different bending conditions. Our results revealed the possibility of 1D ZnS/CdS heterostructures for application in the detection of UV and visible light. The main advantages of the heterostructures have great potential application for future optoelectronic devices. PMID- 26879190 TI - Right Ventricular Deformation Analyses Using a Three-Dimensional Speckle-Tracking Echocardiographic System Specialized for the Right Ventricle. AB - BACKGROUND: Given the complex morphologic nature of the right ventricle, three dimensional (3D) approaches would be more appropriate for assessing right ventricular (RV) function than two-dimensional approaches. Thus, the investigators have developed a novel 3D speckle-tracking echocardiographic (STE) system specialized for the right ventricle. The aim of this study was to assess the characteristics of RV global and regional deformation as well as changes on stress tests using the 3D STE system in experimental studies. METHODS: In 10 sheep, sonomicrometry crystals were implanted to validate 3D STE data in the RV endocardium of seven RV segments, including the basal and mid anterior, lateral and inferior wall, and outflow free wall. Full-volume 3D STE data sets and sonomicrometric data were acquired at baseline, during pulmonary artery banding (PAB)-induced moderate (peak RV pressure > 40 mm Hg) and severe (peak RV pressure > 60 mm Hg) RV pressure increases, and during propranolol infusion. The 3D STE area change ratio (ACR), longitudinal strain (LS), and circumferential strain (CS) were measured, and RV global and all segmental deformation data were compared between baseline and stress tests. To assess clinical feasibility, 30 control subjects and 11 patients with pulmonary arterial hypertension were enrolled. RESULTS: All combined 3D STE data were significantly correlated with the sonomicrometric data (ACR, R(2) = 0.88; LS, R(2) = 0.84; CS, R(2) = 0.82; P < .001). In all seven segments, the 3D STE data correlated with the sonomicrometric data (R(2) = 0.72-0.90, P < .001). Global ACR and LS data showed significant differences among baseline, moderate PAB, and severe PAB; however, CS differed only between baseline and severe PAB. The magnitudes of segmental deformation in the free wall were larger than those in the septum and apex under all conditions (P < .05) except LS during severe PAB. Segmental analyses also showed similar responses during stress tests; the ACR in each segment differed significantly between conditions. In all but the apical segments, LS showed significant reductions from moderate PAB; in contrast, CS was significantly reduced with severe PAB in all segments. In this clinical study, the acquisition rate of adequate images for analysis of the RV outflow tract was lower (75.6%) compared with the rate in other segments (from 85.4% to 100%). However, the pulmonary arterial hypertension group had lower RV global deformation values than the control group (ACR and LS, P < .001; CS, P = .003), the ACR and LS in basal and middle segments differed significantly between groups, and the outflow and apex did not differ. CONCLUSIONS: A novel 3D STE system specialized for the right ventricle is reliable for RV deformation analyses and may provide additional information about RV global and segmental function. The clinical feasibility of this system is acceptable. PMID- 26879191 TI - Assessment of changes in potential nutrient limitation in an impounded river after application of lanthanum-modified bentonite. AB - With the advent of phosphorus (P)-adsorbent materials and techniques to address eutrophication in aquatic systems, there is a need to develop interpretive techniques to rapidly assess changes in potential nutrient limitation. In a trial application of the P-adsorbent, lanthanum-modified bentonite (LMB) to an impounded section of the Canning River, Western Australia, a combination of potential P, nitrogen (N) and silicon (Si) nutrient limitation diagrams based on dissolved molar nutrient ratios and actual dissolved nutrient concentrations have been used to interpret trial outcomes. Application of LMB resulted in rapid and effective removal of filterable reactive P (FRP) from the water column and also effectively intercepted FRP released from bottom sediments until the advent of a major unseasonal flood event. A shift from potential N-limitation to potential P limitation also occurred in surface waters. In the absence of other factors, the reduction in FRP was likely to be sufficient to induce actual nutrient limitation of phytoplankton growth. The outcomes of this experiment underpins the concept that, where possible in the short-term, in managing eutrophication the focus should not be on the limiting nutrient under eutrophic conditions (here N), but the one that can be made limiting most rapidly and cost-effectively (P). PMID- 26879192 TI - Lymph node hypoplasia is associated with adverse outcomes in node-negative colon cancer using advanced lymph node dissection methods. AB - PURPOSE: Lymph node size as a prognostic parameter has not been investigated well in the past. Recent data, however, have indicated that this parameter could be even more important than the lymph node count. METHODS: Based on the results of earlier studies, we analyzed the lymph node size and number of node-negative colon cancer patients with regard to survival. Data from 115 node-negative cases of colon cancer were analyzed. Lymph nodes with diameters <=5 mm were defined as small, and all other lymph nodes were classified as intermediate/large in size and labeled LN5. All of the cases were categorized according to the number of LN5s. The LN5 very low (LN5vl) group included cases with less than two LN5s. All of the other cases were assigned to the LN5 low/high (LN5l/h) group. RESULTS: The overall survival analysis revealed significantly worse outcomes for the LN5vl group, with a mean survival of 34 months compared to the LN5l/h group, with a mean survival of 40 months (P = 0.022). After adjusting for the pT1/2 and pT3/4 stages, we still found a significant outcome difference (P = 0.012). Multivariate analysis identified LN5vl and T-stage as being independently correlated with the outcome. The vast majority of LN5vl cases (91 %) were located in the left colon. The location itself, however, was not prognostic (P = 0.478). CONCLUSION: LN5 count, as a marker of immune response, could be shown as being prognostic in node negative colon cancer. Patients with low LN5 counts showed poor outcomes. These patients could perhaps profit from adjuvant chemotherapy. PMID- 26879193 TI - Non-Covalent Fluorescent Labeling of Hairpin DNA Probe Coupled with Hybridization Chain Reaction for Sensitive DNA Detection. AB - An enzyme-free signal amplification-based assay for DNA detection was developed using fluorescent hairpin DNA probes coupled with hybridization chain reaction (HCR). The hairpin DNAs were designed to contain abasic sites in the stem moiety. Non-covalent labeling of the hairpin DNAs was achieved when a fluorescent ligand was bound to the abasic sites through hydrogen bonding with the orphan cytosine present on the complementary strand, accompanied by quench of ligand fluorescence. As a result, the resultant probes, the complex formed between the hairpin DNA and ligand, showed almost no fluorescence. Upon hybridization with target DNA, the probe underwent a dehybridization of the stem moiety containing an abasic site. The release of ligand from the abasic site to the solution resulted in an effective fluorescent enhancement, which can be used as a signal. Compared with a sensing system without HCR, a 20-fold increase in the sensitivity was achieved using the sensing system with HCR. The fluorescent intensity of the sensing system increased with the increase in target DNA concentration from 0.5 nM to 100 nM. A single mismatched target ss-DNA could be effectively discriminated from complementary target DNA. Genotyping of a G/C single nucleotide polymorphism of polymerase chain reaction (PCR) products was successfully demonstrated with the sensing system. Therefore, integrating HCR strategy with non-covalent labeling of fluorescent hairpin DNA probes provides a sensitive and cost-effective DNA assay. PMID- 26879195 TI - Recessive mutations of TMC1 associated with moderate to severe hearing loss. AB - TMC1 encodes a protein required for the normal function of mechanically activated channels that enable sensory transduction in auditory and vestibular hair cells. TMC1 protein is localized at the tips of the hair cell stereocilia, the site of conventional mechanotransduction. In many populations, loss-of-function recessive mutations of TMC1 are associated with profound deafness across all frequencies tested. In six families reported here, variable moderate-to-severe or moderate-to profound hearing loss co-segregated with STR (short tandem repeats) markers at the TMC1 locus DFNB7/11. Massively parallel and Sanger sequencing of genomic DNA revealed each family co-segregating hearing loss with a homozygous TMC1 mutation: two reported mutations (p.R34X and p.R389Q) and three novel mutations (p.S596R, p.N199I, and c.1404 + 1G > T). TMC1 cDNA sequence from affected subjects homozygous for the donor splice site transversion c.1404 + 1G > T revealed skipping of exon 16, deleting 60 amino acids from the TMC1 protein. Since the mutations in our study cause less than profound hearing loss, we speculate that there is hypo-functional TMC1 mechanotransduction channel activity and that other even less damaging variants of TMC1 may be associated with more common mild-to severe sensorineural hearing loss. PMID- 26879194 TI - Regulation of the fungal secretome. AB - The ability of countless representatives of the Kingdom Fungi to adapt to and proliferate in diverse environments is facilitated by regulation of their secretomes to respond to changes in environmental conditions and to mediate interactions with other organisms. Secretome changes often fulfill common functions of nutrient acquisition, facilitation of host/symbiont interactions, cell wall modification, and optimization of the enzyme suite to adapt to new environmental resources. In this review, we expand on our recent work on signaling and the secretome in the pathogenic fungus Cryptococcus neoformans to consider a range of selected examples of regulation of fungal secretomes. These examples include the impact of carbon source and aspects of the response to plant and animal hosts. Additionally, the influence of key protein kinases (e.g., Pka1, Snf1) and transcription factors (e.g., Rim101/PacC) is highlighted to illustrate some underlying regulatory factors influencing the secretome. Although there is a wealth of information about fungal secretomes from both experimentation and genome sequence mining, there are also major gaps in our knowledge about the complete composition of fungal secretomes and mechanisms of dynamic change. For example, a more comprehensive understanding of the composition and regulation of the secretome will require consideration of the emerging roles of unconventional secretion and extracellular vesicles in delivering proteins outside the cell. Overall, changes in the secretome are well documented in diverse fungi and the underlying mechanisms are currently under investigation; however, there remain unknown steps in the regulation of secretory pathways and gaps in understanding the regulation of unconventional secretion, which warrant further research. PMID- 26879197 TI - The association of severity of retinal vascular changes and cardiac remodelling in systemic hypertension. AB - OBJECTIVES: The aim of the study was to explore the association between hypertensive retinopathy, grades of retinopathy and cardiac remodelling. METHODS: This was a cross-sectional observational study. A total of 500 consecutive hypertensive adults from the in-patient population were studied for the presence of hypertensive retinopathy by dilated fundoscopy. The presence of cardiac remodelling due to hypertension was studied both by electrocardiography (ECG) and echocardiography. Hypertensive target organ damage in other organs was also screened. In addition, the association of grades of hypertensive retinopathy with target organ damage was also analyzed. RESULTS: Systolic blood pressure (BP) at presentation and duration of hypertension showed no relationship with markers of hypertensive heart disease. However, diastolic BP was significantly higher in patients with retinopathy. Hypertensive retinopathy was diagnosed in 324 subjects of whom 90 had grades 3 and 4 retinopathy. Patients with grades 3 and 4 retinopathy had significant associations with ECG evidence of left ventricular (LV) strain pattern and left atrial enlargement, and a weaker association with left ventricular hypertrophy (LVH) using QRS voltage criteria (Sokolov-Lyon). On echocardiography, grades 3 and 4 retinopathy were significantly associated with LVH, left atrial enlargement and reduced left ventricular ejection fraction (LVEF), as well as with higher creatinine values. A large number of these patients presented with heart failure. Cardiac remodelling was not seen in patients without retinopathy and was uncommon in patients with grades 1 and 2 retinopathy. CONCLUSION: Grades 3 and 4 retinopathy demonstrated a significant association with LV strain pattern and left atrial enlargement on ECG, LVH and reduced LVEF on echocardiography as well as with heart failure. There was no relationship with systolic BP and duration of hypertension, while diastolic BP showed a significant positive correlation. Signs of hypertensive heart disease were practically absent in patients without hypertensive retinopathy and uncommon in those with grade 1-2 alterations. PMID- 26879196 TI - Intracoronary Imaging in the Detection of Vulnerable Plaques. AB - Coronary artery disease is the result of atherosclerotic changes to the coronary arterial wall, comprising endothelial dysfunction, vascular inflammation and deposition of lipid-rich macrophage foam cells. Certain high-risk atherosclerotic plaques are vulnerable to disruption, leading to rupture, thrombosis and the clinical sequelae of acute coronary syndrome. Though recognised as the gold standard for evaluating the presence, distribution and severity of atherosclerotic lesions, invasive coronary angiography is incapable of identifying non-stenotic, vulnerable plaques that are responsible for adverse cardiovascular events. The recognition of such limitations has impelled the development of intracoronary imaging technologies, including intravascular ultrasound, optical coherence tomography and near-infrared spectroscopy, which enable the detailed evaluation of the coronary wall and atherosclerotic plaques in clinical practice. This review discusses the present status of invasive imaging technologies; summarises up-to-date, evidence-based clinical guidelines; and addresses questions that remain unanswered with regard to the future of intracoronary plaque imaging. PMID- 26879198 TI - Fatal Cyberlindnera fabianii fungemia in a patient with mixed phenotype acute leukemia after umbilical cord blood transplantation. AB - We report a case of Cyberlindnera fabianii fungemia after umbilical cord blood transplantation (CBT). A 69-year-old woman was diagnosed as having mixed phenotype acute leukemia. The patient received CBT for primary refractory disease. After preconditioning chemotherapy, the patient's condition deteriorated, leading to acute respiratory failure from capillary leak syndrome and consequent admittance to the intensive care unit. The patient recovered temporarily following the administration of noninvasive positive pressure ventilation and continuous hemodiafiltration, but died of fungemia with the presence of yeast-like cells 15 days post-CBT. The yeast-like cells were analyzed by sequencing of the D1/D2 domain of the large subunit and the internal transcribed spacer domain, and were identified as C. fabianii. This case shows that molecular genetic-based methods may be effective for detecting undetermined invasive fungal infections in stem cell transplantation settings. PMID- 26879199 TI - Chronic (3-Weeks) Treatment of Estrogen (17beta-Estradiol) Enhances Working and Reference Memory in Ovariectomized Rats: Role of Acetylcholine. AB - Recently there has been a growing interest in the effects of estrogen on cognitive functions. In this study, we aimed to examine 17beta-estradiol treatment on working and reference memory in ovariectomized rats. We also examined the changes in the acetylcholine (ACh) levels in the brain areas associated with learning and memory. The study was performed on Sprague-Dawley type 3-month-old female rats. The rats were divided into four groups as control, ovariectomy (OVX), and OVX and estrogen treatment (10 ug/day i.p. 17beta estradiol) groups for 3 (OVX + E3) and 21 days OVX + E21). The rats were trained on eight arm radial maze task with eight arms baited to assess spatial memory, in addition four arms baited to assess both working and reference memory performances. The electron microscope images of the ACh vesicles in the frontal cortex, temporal cortex and hippocampus areas of the brain which are important regions for learning and memory were screened. Results showed that long term 17beta-estradiol treatment has positive effects on both reference memory and working memory and that ACh vesicles increased in the examined brain areas, especially in hippocampus. Our results suggest that 3 weeks 17beta-estradiol treatment may have an ameliorative effect on the memory through the central cholinergic system. PMID- 26879200 TI - Continuous treatment with odanacatib for up to 8 years in postmenopausal women with low bone mineral density: a phase 2 study. AB - The efficacy and safety of weekly oral odanacatib (ODN) 50 mg for up to 8 years were assessed in postmenopausal women with low bone mineral density (BMD). Treatment with ODN for up to 8 years resulted in continued or maintained increases in BMD at multiple sites and was well tolerated. INTRODUCTION: ODN is a selective inhibitor of cathepsin K. In a 2-year phase 2b study (3/10/25/50 mg ODN once weekly [QW] or placebo) and extensions (50 mg ODN QW or placebo), ODN treatment for 5 years progressively increased BMD and decreased bone resorption markers in postmenopausal women with low BMD ( ClinicalTrials.gov NCT00112437). METHODS: In this prespecified interim analysis at year 8 of an additional 5-year extension (years 6 to 10), patients (n = 117) received open-label ODN 50 mg QW plus weekly vitamin D3 (5600 IU) and calcium supplementation as needed. Primary end points were lumbar spine BMD and safety. Patients were grouped by ODN exposure duration. RESULTS: Mean (95 % confidence interval [CI]) lumbar spine BMD changes from baseline were 4.6 % (2.4, 6.7; 3-year continuous ODN exposure), 12.9 % (8.1, 17.7; 5 years), 12.8 % (10.0, 15.7; 6 years), and 14.8 % (11.0, 18.6; 8 years). Similar patterns of results were observed for BMD of trochanter, femoral neck, and total hip versus baseline. Geometric mean changes from baseline to year 8 for bone resorption markers were approximately -50 % (uNTx/Cr) and -45 % (sCTx), respectively (all groups); bone formation markers remained near baseline levels. No osteonecrosis of the jaw, delayed fracture union, or morphea-like skin reactions were reported. CONCLUSIONS: Treatment with ODN for up to 8 years resulted in gains in BMD at multiple sites. Bone resorption markers remained reduced, with no significant change observed in bone formation markers. Treatment with ODN for up to 8 years was well tolerated. PMID- 26879202 TI - Biodegradation of tetramethylammonium hydroxide (TMAH) in completely autotrophic nitrogen removal over nitrite (CANON) process. AB - This study conducted a completely autotrophic nitrogen removal over nitrite (CANON) process in a continuous anoxic upflow bioreactor to treat synthetic wastewater with TMAH (tetramethylammonium hydroxide) ranging from 200 to 1000mg/L. The intermediates were analyzed for understanding the metabolic pathway of TMAH biodegradation in CANON process. In addition, (15)N-labeled TMAH was used as the substrate in a batch anoxic bioreactor to confirm that TMAH was converted to nitrogen gas in CANON process. The results indicated that TMAH was almost completely biodegraded in CANON system at different influent TMAH concentrations of 200, 500, and 1000mg/L. The average removal efficiencies of total nitrogen were higher than 90% during the experiments. Trimethylamine (TMA) and methylamine (MA) were found to be the main biodegradation intermediates of TMAH in CANON process. The production of nitrogen gas with (15)N-labeled during the batch anaerobic bioreactor indicated that CANON process successfully converted TMAH into nitrogen gas. PMID- 26879201 TI - Lower leg muscle density is independently associated with fall status in community-dwelling older adults. AB - Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17 % increase in odds of reporting a fall, independent of functional mobility. INTRODUCTION: Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status. METHODS: Cross-sectional observational study of 183 men and women aged 60 98 years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities. RESULTS: Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6 mg/cm(3)) independently reduced the odds of being a faller by 19 % (OR 0.81 [95 % CI 0.67 to 0.97]), and every 1 s longer TUG test time (mean 9.8, SD 2.6 s) independently increased the odds by 17 % (OR 1.17 [95 % CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95 % CI 0.87 to 0.99]) and muscle density (OR 0.83 [95 % CI 0.69 to 0.99]) were independently associated with fall status. CONCLUSIONS: Muscle density was associated with fall status, independent of functional mobility. Muscle density may compliment functional mobility tests as a biometric outcome for assessing fall risk in well-functioning older adults. PMID- 26879203 TI - Phosphorus extraction and sludge dissolution by acid and alkali treatments of polyaluminum chloride (PAC) treated wastewater sludge. AB - Phosphorus (P) leaching characteristics of polyaluminium chlorides (PAC) treated wastewater sludge was investigated by wet chemicals (acid and alkali). Sludge fractionation showed non-apatite inorganic P was the dominant P (90.9% of TP) while apatite P only accounted for 3.7%. After 2h extraction with 1N NaOH or 2N HCl, 80.5% and 77.9% of total P was leached, while sludge dissolution reached 72.7% and 75.6%, respectively. Kinetic study with HCl and NaOH showed that P release and sludge dissolution follow first order reaction with rate constants of 0.50 and 0.35min(-1) (P release) and 0.47*10(-2) and 0.15*10(-2)min(-1) (sludge dissolution), respectively. Sequential extraction by NaOH/HCl leached 91.7% of the total P. This study will help in understanding the P release behavior of the PAC treated wastewater sludge. PMID- 26879204 TI - Effects of processing conditions on biocrude yields from fast hydrothermal liquefaction of microalgae. AB - This study investigated the effects of algae species, reaction time, and reactor loading on the biocrude yield from fast hydrothermal liquefaction (HTL) of microalgae. Fast HTL reaction times were always less than 2 min and employed rapid heating and nonisothermal conditions. The highest biocrude yield obtained was 67+/-5 wt.% (dry basis). With all other process variables fixed, increasing the reaction time in a 600 degrees C sand bath by 15 s increments led to a rapid increase in biocrude yield between 15 and 45 s. At longer times, the biocrude yield decreased. Low reactor loadings generally gave higher biocrude yields than did higher loadings. The low reactor loadings may facilitate biocrude production by facilitating cell rupture and/or increasing the effective concentration of algal cells in the hot, compressed water in the reactor. PMID- 26879205 TI - Effect of powdered activated carbon on integrated submerged membrane bioreactor nanofiltration process for wastewater reclamation. AB - The aim of this study was to determine the effect of powdered activated carbon (PAC) on the overall performance of a submerged membrane bioreactor (SMBR) system integrated with nanofiltration (NF) for wastewater reclamation. It was found that the trans-membrane pressure of SMBR increased continuously while that of the SMBR with PAC was more stable, mainly because water could still pass through the PACs and membrane even though foulants adhered on the PAC surface. The presence of PAC was able to mitigate fouling in SMBR as well as in NF. SMBR-NF with PAC obtained a higher flux of 8.1 LMH compared to that without PAC (6.6 LMH). In addition, better permeate quality was obtained with SMBR-NF integrated process added with PAC. The present results suggest that the addition of PAC in integrated SMBR-NF process could possibly lead to satisfying water quality and can be operated for a long-term duration. PMID- 26879206 TI - An Ultra-High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4. AB - Revealing chemokine receptor CXCR4 expression, distribution, and internalization levels in different cancers helps to evaluate cancer progression or prognosis and to set personalized treatment strategy. We here describe a sensitive and high throughput immunoassay for determining CXCR4 expression and distribution in cancer cells. The assay is accessible to a wide range of users in an ordinary lab only by dip-coating poly(styrene-co-N-isopropylacrylamide) spheres on the glass substrate. The self- assembled spheres form three-dimensional photonic colloidal crystals which enhance the fluorescence of CF647 and Alexa Fluor 647 by a factor of up to 1000. CXCR4 in cells is detected by using the sandwich immunoassay, where the primary antibody recognizes CXCR4 and the secondary antibody is labeled with CF647. With the newly established assay, we quantified the total expression of CXCR4, its distribution on the cell membrane and cytoplasm, and revealed their internalization level upon SDF-1alpha activation in various cancer cells, even for those with extremely low expression level. PMID- 26879208 TI - Multi-responsive coordination polymers utilising metal-stabilised, dynamic covalent imine bonds. AB - We report how the combination of dynamic covalent imine bonds and coordination bonds in a single polymer material not only imparts enhanced stability to the final polymer, but also allows the material to be sensitive to a range of stimuli, offering more fine-grained control over its properties. PMID- 26879207 TI - Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1. AB - PURPOSE: The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age- and obesity-related chemokine monocyte chemoattractant protein-1 (MCP-1). METHODS: Ovaries from reproductive-aged and older C57BL/6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR). RESULTS: In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs. CONCLUSION: These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP 1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively. PMID- 26879209 TI - Trachelogenin, a novel inhibitor of hepatitis C virus entry through CD81. AB - Although much progress has been made in antiviral agents against hepatitis C virus (HCV) in recent years, novel HCV inhibitors with improved efficacy, optimized treatment duration and more affordable prices are still urgently needed. Here, we report the identification of a natural plant-derived lignan, trachelogenin (TGN), as a potent entry inhibitor of HCV without genotype specificity, and with low cytotoxicity. TGN was extracted and purified from Caulis trachelospermi, a traditional Chinese herb with anti-inflammatory and analgesic effects. A crucial function of TGN was the inhibition of HCV entry during a post-binding step without affecting virus replication, translation, assembly and release. TGN blocked virus infection by interfering with the normal interactions between HCV glycoprotein E2 and the host entry factor CD81, which are key processes for valid virus entry. In addition, TGN diminished HCV cell-to cell spread and exhibited additional synergistic effects when combined with IFN or telaprevir. In conclusion, this study highlights the effect of a novel HCV entry inhibitor, TGN, which has a target that differs from those of the current antiviral agents. Therefore, TGN is a potential candidate for future cocktail therapies to treat HCV-infected patients. PMID- 26879211 TI - Behavioral disorders after traumatic brain injury: Why a special issue in the Annals of Physical and Rehabilitation Medicine? PMID- 26879212 TI - Cross-cultural equivalence in translation of the oral health impact profile: how to interpret the final score? AB - The oral health impact profile (OHIP) is one of the most widely known oral health related quality of life instruments. In Community Dentistry and Oral Epidemiology, MacEntee and Brondani report the results of a systematic review to identify acceptable methods for translating psychometric instruments for cross cultural equivalence of the OHIP scale. But in no study has unidimensionality, one aspect of the validity of the internal structure of the scale, been verified, whereas it is a major psychometric step. In the absence of the study of unidimensionality, it is difficult to interpret the final score. The methodology of transcultural validation of the OHIP could be improved, and the study of the unidimensionality is a psychometrically necessary step for the interpretation of the finale score. PMID- 26879216 TI - Decreased Cystatin C-Estimated Glomerular Filtration Rate Is Correlated with Prolonged Hospital Stay in Transient Tachypnea of Newborn Infants. AB - BACKGROUND: Transient tachypnea of the newborn (TTN) is a benign disorder with a variable clinical course that often leads to hospitalization. The aim of this study was to assess and validate the relationship between the serum cystatin C level and symptom duration in infants with TTN. METHODS: Forty newborns presenting with TTN and who had undergone serum cystatin C (Cys C) tests on the first day of admission to the Kyung Hee University Hospital (Seoul, Korea) from 2009 to 2013 were included. The serum Cys C level, creatinine (Cr) level, estimated glomerular filtration rate (eGFR), and tachypnea duration were correlated retrospectively. RESULTS: The median gestation period was 37.8 +/- 3.8 weeks and the mean birth weight was 3.2 +/- 0.4 kg. Tachypnea duration was 3.3 +/ 2.0 days. Serum Cys C and Cr levels were 1.7 +/- 0.2 mg/L and 0.8 +/- 1.2 mg/dL, respectively. Tachypnea duration was significantly positively correlated with the serum levels of Cys C and significantly negatively correlated with Cys C-based eGFR (p = 0.016), but was not significantly correlated with the serum Cr level or Cr-based eGFR. When tachypnea duration was compared between infants with Cys C level <1.6 mg/L (n = 15; Group A) and infants with Cys C level >= 1.6 mg/L (n = 25; Group B), the symptom duration was significantly shorter in Group A infants (p = 0.011). CONCLUSION: Tachypnea duration was shorter with higher Cys C-based eGFR in infants with TTN. PMID- 26879217 TI - Acetate tape impression test for diagnosis of notoedric mange in cats. AB - Objectives The aim of this study was to compare the sensitivity of acetate tape impression with skin squeezing and superficial skin scraping methods for the diagnosis of burrowing mites ( Notoedres cati) in cats. Methods Samples were collected from 50 cats showing signs of notoedric mange. The most affected region was selected for sampling using acetate tape impression with skin squeezing, and superficial skin scraping. Results No significant difference was observed in the number of mites found by both methods, regardless of the stage of development of the mite. The tests showed a high correlation to the total number of mites (r = 0.928). However, in two animals it was possible to confirm the presence of N cati only by the acetate tape impression test. Conclusions and relevance We conclude that the acetate tape impression test is a good method for confirming the presence of N cati in cats. In our experience, this technique is as sensitive as superficial skin scraping, even in animals presenting with a low infestation. Moreover, the technique is less traumatic and allows the collection of clinical specimens in more sensitive locations, such as the eyelids, lips and paws. PMID- 26879218 TI - Inhibitory Effect of 8-Halogenated 7-Deaza-2'-deoxyguanosine Triphosphates on Human 8-Oxo-2'-deoxyguanosine Triphosphatase, hMTH1, Activities. AB - hMTH1 (8-oxo-2'-deoxyguanine triphosphatase) hydrolyzes oxidized nucleoside triphosphates; its presence is non-essential for survival of normal cells but is required for survival of cancer cells. In this study, 8-halogenated-7-deaza-2' deoxyguanosine triphosphate (8-halogenated-7-deazadGTP) derivatives were synthesized. Interestingly, these triphosphates were poor substrates for hMTH1, but exhibited strong competitive inhibition against hMTH1 at nanomolar levels. This inhibitory effect is attributed to slower rate of hydrolysis, possibly arising from enzyme structural changes, specifically different stacking interactions with 8-halogenated-7-deazadGTP. This is the first example of using nucleotide derivatives to inhibit hMTH1, thus demonstrating their potential as antitumor agents. PMID- 26879210 TI - Shared and unique mechanisms underlying binge eating disorder and addictive disorders. AB - Scientific interest in "food addiction" is growing, but the topic remains controversial. One critique of "food addiction" is its high degree of phenotypic overlap with binge eating disorder (BED). In order to examine associations between problematic eating behaviors, such as binge eating and "food addiction," we propose the need to move past examining similarities and differences in symptomology. Instead, focusing on relevant mechanisms may more effectively determine whether "food addiction" contributes to disordered eating behavior for some individuals. This paper reviews the evidence for mechanisms that are shared (i.e., reward dysfunction, impulsivity) and unique for addiction (i.e., withdrawal, tolerance) and eating disorder (i.e., dietary restraint, shape/weight concern) frameworks. This review will provide a guiding framework to outline future areas of research needed to evaluate the validity of the "food addiction" model and to understand its potential contribution to disordered eating. PMID- 26879219 TI - 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress. AB - Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit (GCLM), and NAD(P)H: quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its alpha,beta-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. PMID- 26879220 TI - Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo. AB - The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners in vitro. Thus, the goal of the present study was to establish an animal model of NAC-mediated protection in which to dissect the underlying mechanism. Mice were infused intrastriatally with the oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 MUg) and administered NAC intraperitoneally (100mg/kg). NAC-treated animals exhibited higher levels of the dopaminergic terminal marker tyrosine hydroxylase (TH) in the striatum 10d after 6-OHDA. As TH expression is subject to stress induced modulation, we infused the tracer FluoroGold into the striatum to retrogradely label nigrostriatal projection neurons. As expected, nigral FluoroGold staining and cell counts of FluoroGold(+) profiles were both more sensitive measures of nigrostriatal degeneration than measurements relying on TH alone. However, NAC failed to protect dopaminergic neurons 3 weeks following 6 OHDA, an effect verified by four measures: striatal TH levels, nigral TH levels, nigral TH(+) cell counts, and nigral FluoroGold levels. Some degree of mild toxicity of FluoroGold and NAC was evident, suggesting that caution must be exercised when relying on FluoroGold as a neuron-counting tool and when designing experiments with long-term delivery of NAC--such as clinical trials on patients with chronic disorders. Finally, the strengths and limitations of the tools used to define nigrostriatal degeneration are discussed. PMID- 26879221 TI - Picky eating in preschool children: Associations with dietary fibre intakes and stool hardness. AB - It has been suggested that constipation may be associated with picky eating. Constipation is a common condition in childhood and a low intake of dietary fibre may be a risk factor. Differences in fibre intake between picky and non-picky children and its relation to stool consistency is currently not well-understood. Children enrolled in the Avon Longitudinal Study of Parents and Children identified as picky eaters (PE) were compared with non-picky eaters (NPE): (1) to determine dietary fibre intake at 38 months; (2) to investigate whether any difference in dietary fibre intake was predictive of usual stool hardness at 42 months. PE was identified from questionnaires at 24 and 38 months. Usual stool hardness was identified from a questionnaire at 42 months. Dietary intake was assessed at 38 months with a food frequency questionnaire. Dietary fibre intake was lower in PE than NPE (mean difference -1.4 (95% CI -1.6, -1.2) g/day, p < 0.001). PE was strongly associated with dietary fibre intake (adjusted regression model; unstandardised B -1.44 (95% CI -1.62, -1.24) g/day, p < 0.001). PE had a lower percentage of fibre from vegetables compared with NPE (8.9% vs 15.7%, respectively, p < 0.001). There was an association between PE and usually having hard stools (adjusted multinomial model; OR 1.31, 95% CI 1.07, 1.61; p = 0.010). This was attenuated when dietary fibre was included in the model, suggesting that fibre intake mediated the association (OR 1.16, 95% CI 0.94, 1.43, p = 0.180). Picky eating in 3-year-old children was associated with an increased prevalence of usually having hard stools. This association was mediated by low dietary fibre intake, particularly from vegetables, in PE. For children with PE, dietary advice aimed at increasing fibre intake may help avoid hard stools. PMID- 26879222 TI - Examination of the reliability and validity of the Mindful Eating Questionnaire in pregnant women. AB - OBJECTIVE: Mindfulness is theorized to affect the eating behavior and weight of pregnant women, yet no measure has been validated during pregnancy. METHODS: This study qualitatively and quantitatively evaluated the reliability and validity of the Mindful Eating Questionnaire (MEQ) in overweight and obese pregnant women. Participants completed focus groups and cognitive interviews. The MEQ was administered twice to measure test-retest reliability. The Eating Inventory (EI) and Mindful Attention Awareness Scale (MAAS) were administered to assess convergent validity, and the Neighborhood Environment Walkability Scale (NEWS) assessed discriminant validity. RESULTS: Participants were 20 +/- 8 weeks gestation (mean +/- SD), 30 +/- 2 years old, and 55% were obese. The MEQ total score had good test-retest reliability (r = .85). The total score internal consistency reliability was poor (Cronbach's alpha = .56). The external cues subscale (ECS) was not internally consistent (alpha = .31). Other subscales ranged from alpha = .59-.68. When the ECS was excluded, the MEQ total score internal consistency was acceptable (alpha = .62). Convergent validity was supported by the MEQ total score (with and without ECS) correlating significantly with the MAAS and the EI disinhibition and hunger subscales. Discriminant validity of the MEQ was supported by the MEQ and NEWS total scores and subscales not being significantly correlated. The quantitative results were supported by the qualitative context and content analysis. CONCLUSION: With the exception of the ECS, the MEQ's reliability and validity was supported in pregnant women, and most of the subscales were more robust in pregnant women than in the original sample of healthy adults. The MEQ's use with overweight and obese pregnant women is supported. PMID- 26879223 TI - A qualitative evaluation of the challenges faced by dieticians when interviewing children. AB - BACKGROUND: Investigative interviewing is a critical and challenging skill involved in the assessment and design of appropriate interventions for children's dietary problems. The current study provided an evaluation of the challenges faced by professional dieticians when conducting child investigative interviews, in the hope that this would provide a framework for the development of further guidance and resources in this important area. METHODS: Fourteen professional dieticians were interviewed; they were asked about the information that they needed to elicit from children in particular situations and the questions that they would ask to do so. They were also asked to describe the strengths and limitations of the techniques that they used. RESULTS: The results revealed that professionals faced three main challenges. The first challenge was eliciting information from children who did not want to answer questions. The second challenge was determining the level of accuracy in children's (and caregivers') responses. The third challenge was eliciting very specific information in particular situations, such as determining the cause of an allergic reaction. CONCLUSIONS: Overall, professionals had difficulty articulating the questions that they would use to elicit the information that they required; indeed, their responses focused more on the content that they wanted to elicit (such as specific details) rather than the overall process that they would use to do so. Professionals may benefit from the development of guidelines to assist them in their interviews with children, based on what is currently known about interviewing children generally. PMID- 26879224 TI - Effects of financial incentives for the purchase of healthy groceries on dietary intake and weight outcomes among older adults: A randomized pilot study. AB - Providing financial incentives can be a useful behavioral economics strategy for increasing fruit and vegetable intake among consumers. It remains to be determined whether financial incentives can promote intake of other low energy dense foods and if consumers who are already using promotional tools for their grocery purchases may be especially responsive to receiving incentives. This randomized controlled trial tested the effects of offering financial incentives for the purchase of healthy groceries on 3-month changes in dietary intake, weight outcomes, and the home food environment among older adults. A secondary aim was to compare frequent coupon users (FCU) and non-coupon users (NCU) on weight status, home food environment, and grocery shopping behavior. FCU (n = 28) and NCU (n = 26) were randomly assigned to either an incentive or a control group. Participants in the incentive group received $1 for every healthy food or beverage they purchased. All participants completed 3-day food records and a home food inventory and had their height, weight, and waist circumference measured at baseline and after 3 months. Participants who were responsive to the intervention and received financial incentives significantly increased their daily vegetable intake (P = 0.04). Participants in both groups showed significant improvements in their home food environment (P = 0.0003). No significant changes were observed in daily energy intake or weight-related outcomes across groups (P < 0.12). FCU and NCU did not differ significantly in any anthropometric variables or the level at which their home food environment may be considered 'obesogenic' (P > 0.73). Increased consumption of vegetables did not replace intake of more energy-dense foods. Incentivizing consumers to make healthy food choices while simultaneously reducing less healthy food choices may be important. PMID- 26879225 TI - Microwave fields have little effect on alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson's disease. AB - Potential health effects of radiofrequency (RF) radiation from mobile phones arouse widespread public concern. RF fields from handheld devices near the brain might trigger or aggravate brain tumors or neurodegenerative diseases such as Parkinson's disease (PD). Aggregation of neural alpha-synuclein (S) is central to PD pathophysiology, and invertebrate models expressing human S have helped elucidate factors affecting the aggregation process. We have recently developed a transgenic strain of Caenorhabditis elegans carrying two S constructs: SC tagged with cyan (C) blue fluorescent protein (CFP), and SV with the Venus (V) variant of yellow fluorescent protein (YFP). During S aggregation in these SC+SV worms, CFP, and YFP tags are brought close enough to allow Foerster Resonance Energy Transfer (FRET). As a positive control, S aggregation was promoted at low Hg(2+) concentrations, whereas higher concentrations activated stress-response genes. Using two different exposure systems described previously, we tested whether RF fields (1.0 GHz CW, 0.002-0.02 W kg(-1); 1.8 GHz CW or GSM, 1.8 W kg(-1)) could influence S aggregation in SC+SV worms. YFP fluorescence in similar SV-only worms provided internal controls, which should show opposite changes due to FRET quenching during S aggregation. No statistically significant changes were observed over several independent runs at 2.5, 24, or 96 h. Although our worm model is sensitive to chemical promoters of aggregation, no similar effects were attributable to RF exposures. PMID- 26879227 TI - The location of pain and urgency sensations during cystometry. AB - AIMS: The relationship between bladder pain and urinary urgency sensations is poorly understood. We analyzed the relationship between locations and intensities of urgency and pain sensations felt during filling cystometry. METHODS: Participants completed the King's Health Questionnaire (KHQ) to indicate presence of bladder pain or urgency. During cystometry, participants scored the intensity of urgency and pain, both in the suprapubic and the urethral region, on a VAS scale of 0-10 at a baseline, at first desire, normal desire, strong desire to void, and at maximum cystometric capacity during filling. We allocated the participants to six groups; those reporting urgency or not, pain or not, both symptoms and neither. Friedman's Test was used to ascertain if all scores increased significantly, the Wilcoxon Signed Rank Test was used to demonstrate the difference between scores, and agreement for findings during cystometry was tested with Mann-Whitney U. RESULTS: A total of 68 women participated; 38 participants reported pain, 57 reported urgency, and 33 reported both symptoms. Pain and urgency scores significantly increased during cystometry (P < 0.0001). For participants reporting pain, suprapubic pain was rated significantly higher than urethral pain. Participants reporting both symptoms, felt more urgency than pain, and again pain more suprapubically than urethrally. Participants reporting only urgency scored suprapubic and urethral urgency similarly at all desires. CONCLUSIONS: Pain and urgency are well differentiated sensations and are felt at different locations although pain is seemingly easier localized. Neurourol. Urodynam. 36:620-625, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26879228 TI - The endoscopic transseptal approach for choanal atresia repair. AB - BACKGROUND: There are many standard repair options for choanal atresia including puncture, dilatation and drilling of the atretic plate. Most of these techniques involve postoperative stenting, which may promote granulation and scarring, with possible progression to restenosis. This article describes a novel approach for choanal atresia repair without postoperative stenting. METHODS: This article describes our experience with this choanal atresia repair technique utilized in 16 pediatric patients and 1 adult patient across multiple tertiary pediatric and rhinology centers during 2008 through 2015. Seven cases were bilateral and 10 were unilateral. Surgery was performed using an endoscopic transseptal approach with preservation of the mucosa and creation of flaps. No stents or packing was used. The main outcome measures were: response to treatment based on endoscopic examination, need for further revision and incidence of complications. RESULTS: All patients underwent routine postoperative endoscopic inspection of their nasal cavity, postnasal space, and assessment of neochoanal patency. The neochoanae of all patients remained patent to a minimum follow-up duration of 9 months with most patients follow up for 2 years or more. Two neonatal patients required transfusion postoperation from intraoperative bleeding. Two pediatric patients developed postoperative respiratory complications. One patient required revision surgery for nasal vestibule scarring from incision made on the nasal alar to facilitate the initial endoscopic approach. CONCLUSION: This novel endoscopic transseptal repair technique is effective in the management of choanal atresia. Careful fashioning of mucosal flaps and the omission of stenting has resulted in lasting patency of the neochoanae. PMID- 26879231 TI - Ion-Pair SN 2 Substitution: Activation Strain Analyses of Counter-Ion and Solvent Effects. AB - The ion-pair SN 2 reactions of model systems MnF(n-1) +CH3Cl(M(+) =Li(+), Na(+), K(+), and MgCl(+); n=0, 1) have been quantum chemically explored by using DFT at the OLYP/6-31++G(d,p) level. The purpose of this study is threefold: 1) to elucidate how the counterion M(+) modifies ion-pair SN 2 reactivity relative to the parent reaction F(-) +CH3Cl; 2) to determine how this influences stereochemical competition between the backside and frontside attacks; and 3) to examine the effect of solvation on these ion-pair SN2 pathways. Trends in reactivity are analyzed and explained by using the activation strain model (ASM) of chemical reactivity. The ASM has been extended to treat reactivity in solution. These findings contribute to a more rational design of tailor-made substitution reactions. PMID- 26879229 TI - Endothelial Mineralocorticoid Receptor Mediates Diet-Induced Aortic Stiffness in Females. AB - RATIONALE: Enhanced activation of the mineralocorticoid receptors (MRs) in cardiovascular tissues increases oxidative stress, maladaptive immune responses, and inflammation with associated functional vascular abnormalities. We previously demonstrated that consumption of a Western diet (WD) for 16 weeks results in aortic stiffening, and that these abnormalities were prevented by systemic MR blockade in female mice. However, the cell-specific role of endothelial cell MR (ECMR) in these maladaptive vascular effects has not been explored. OBJECTIVE: We hypothesized that specific deletion of the ECMR would prevent WD-induced increases in endothelial sodium channel activation, reductions in bioavailable nitric oxide, increased vascular remodeling, and associated increases in vascular stiffness in females. METHODS AND RESULTS: Four-week-old female ECMR knockout and wild-type mice were fed either mouse chow or WD for 16 weeks. WD feeding resulted in aortic stiffness and endothelial dysfunction as determined in vivo by pulse wave velocity and ex vivo by atomic force microscopy, and wire and pressure myography. The WD-induced aortic stiffness was associated with enhanced endothelial sodium channel activation, attenuated endothelial nitric oxide synthase activation, increased oxidative stress, a proinflammatory immune response and fibrosis. Conversely, cell-specific ECMR deficiency prevented WD induced aortic fibrosis and stiffness in conjunction with reductions in endothelial sodium channel activation, oxidative stress and macrophage proinflammatory polarization, restoration of endothelial nitric oxide synthase activation. CONCLUSIONS: Increased ECMR signaling associated with consumption of a WD plays a key role in endothelial sodium channel activation, reduced nitric oxide production, oxidative stress, and inflammation that lead to aortic remodeling and stiffness in female mice. PMID- 26879234 TI - The industrial archaeology of deep time. AB - For geologists and antiquaries of the late 1850s debates over ancient stone tools were frustrated by a lack of accepted criteria. The artefacts were hard to interpret. It was not self-evident how to judge whether they were ancient or modern, natural or man-made; or indeed whether stone tools could pre-date the use of metal tools at all. Antiquary and papermaker John Evans provided a system that offered to resolve these issues. His criteria and his use of re-enactment, making his own stone implements, gained acceptance among flint experts across fluid disciplinary boundaries and enabled authoritative interpretations of the underdetermined objects. This paper explores how Evans drew on the concerns of his industrial culture to make sense of prehistoric artefacts and support his claim to access the past through his own actions. Situated industrial concerns provided the resources for his flint work: from a patent dispute with astronomer and fellow industrialist Warren de la Rue, through his role in the Victorian arms trade, to the struggle to displace skilled manual labour in his factories. Evans is remembered for pioneering the techniques and classificatory system of modern Palaeolithic archaeology and as one of the founders of the re-enactment science of experimental flint knapping. His work played a significant role in helping reconceive the antiquity of man, yet the system of proof for this grand claim was deeply situated in his industrial culture. This paper explores how the industrial resources of a Victorian papermaker made human history. PMID- 26879233 TI - One-Electron Oxidation of [M(P(t) Bu3 )2 ] (M=Pd, Pt): Isolation of Monomeric [Pd(P(t) Bu3 )2 ](+) and Redox-Promoted C-H Bond Cyclometalation. AB - Oxidation of zero-valent phosphine complexes [M(P(t) Bu3 )2 ] (M=Pd, Pt) has been investigated in 1,2-difluorobenzene solution using cyclic voltammetry and subsequently using the ferrocenium cation as a chemical redox agent. In the case of palladium, a mononuclear paramagnetic Pd(I) derivative was readily isolated from solution and fully characterized (EPR, X-ray crystallography). While in situ electrochemical measurements are consistent with initial one-electron oxidation, the heavier congener undergoes C-H bond cyclometalation and ultimately affords the 14 valence-electron Pt(II) complex [Pt(kappa(2) PC -P(t) Bu2 CMe2 CH2 )(P(t) Bu3 )](+) with concomitant formation of [Pt(P(t) Bu3 )2 H](+) . PMID- 26879232 TI - Alcohol abuse increases the risk of HIV infection and diminishes health status of clients attending HIV testing services in Vietnam. AB - BACKGROUND: Vietnam is among those countries with the highest drinking prevalence. In this study, we examined the prevalence of alcohol use disorders (AUDs) and its associations with HIV risky behaviors, health care utilization, and health-related quality of life (HRQOL) among clients using voluntary HIV testing and counseling services (VCT). METHODS: A cross-sectional survey of 365 VCT clients (71% male; mean age 34) was conducted in Hanoi and Nam Dinh province. AUD and HRQOL were measured using the Alcohol Use Disorders Identification Test Consumption (AUDIT-C), and EuroQol-five dimensions-five levels (EQ-5D-5L). Risky sexual behaviors, concurrent opioid use, and inpatient and outpatient service use were self-reported. RESULTS: 67.2% clients were lifetime ever drinkers of those 62.9% were hazardous drinkers and 82.0% were binge drinkers. There were 48.8% respondents who had >=2 sex partners over the past year and 55.4, 38.3, and 46.1% did not use condom in the last sex with primary/casual/commercial sex partners, respectively. Multivariate models show that AUD was significantly associated with risky sexual behaviors, using inpatient care and lower HRQOL among VCT clients. CONCLUSIONS: AUD was prevalent, was associated with increased risks of HIV infection, and diminished health status among VCT clients. It may be efficient to screen for AUD and refer at-risk clients to appropriate AUD counseling and treatment along with HIV-related services. PMID- 26879230 TI - Selective Targeting of a Novel Epsin-VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis. AB - RATIONALE: We previously reported that vascular endothelial growth factor (VEGF) induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown. OBJECTIVE: The goals for the present study were as follows: (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain whether such determinants were critical for physiological angiogenesis in vivo. METHODS AND RESULTS: Structural modeling uncovered 2 novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Furthermore, we found that the VEGF-induced VEGFR2-epsin interaction promoted casitas B-lineage lymphoma-mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2-epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro, increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing. CONCLUSIONS: Distinct residues in the epsin UIM and VEGFR2 mediate specific interactions between epsin and VEGFR2, in addition to UIM recognition of ubiquitin moieties on VEGFR2. These novel interactions are critical for pathophysiological angiogenesis, suggesting that these sites could be selectively targeted by therapeutics to modulate angiogenesis. PMID- 26879235 TI - Investigation of Toxic Effects of Mushroom Poisoning on the Cardiovascular System. AB - Mushroom poisoning (MP) is a public health problem in many countries. It is well known that consumption of wild mushrooms may cause serious toxicity on renal, hepatic and brain functions. In the literature, however, studies investigating cardiotoxic effects of MP are rare. In this study, we evaluated laboratory and ECG findings of patients and sought for possible toxic effects of MP on the cardiovascular system. During a 2-year period, 175 patients with MP were included in the study. The majority of the poisonings occurred in early summertime. The most common complaint was found to be nausea and vomiting followed by mental status alterations. Methods of treatment were mainly based on gastric lavage, activated charcoal and supportive therapy. The most common ECG abnormalities in the patients with MP were sinus tachycardia, sinus arrhythmia, ST/T inversion, 1st degree AV block and QT prolongation, respectively. Cardiac markers of the patients were found to be normal. Then, patients were divided into two subgroups according to symptom onset after consumption (less than 6 hr and more than 6 hr). When the two groups were compared, prevalence of tachycardia was significantly higher in Group II. Additionally, the interval between mushroom consumption and onset of symptoms was strongly correlated with blood pressure (BP). As this interval prolonged, BP of the patients tended to increase. In conclusion, according to our results, although mechanisms need to be clarified, MP causes hypertension and ECG alterations, particularly tachycardia in patients with late onset symptoms. PMID- 26879237 TI - Continuous manufacturing of tablets with PROMIS-line - Introduction and case studies from continuous feeding, blending and tableting. AB - Drug manufacturing technology is in the midst of modernization and continuous manufacturing of drug products is especially the focus of great interest. The adoption of new manufacturing approaches requires extensive cooperation between industry, regulatory bodies, academics and equipment manufacturers. In this paper we introduce PROMIS-line which is a continuous tableting line built at the University of Eastern Finland, School of Pharmacy, PROMIS-centre. PROMIS-line is modular and tablets can be produced via dry granulation or direct compression. In three case studies, continuous feeding, blending and tablet performance is studied to illustrate some basic features of PROMIS-line. In conclusion, the PROMIS-line is an excellent tool for studying the fundamentals of continuous manufacturing of tablets. PMID- 26879236 TI - Dissecting genetics of cutaneous miRNA in a mouse model of an autoimmune blistering disease. AB - BACKGROUND: MicroRNAs (miRNAs) are small endogenous non-coding RNAs that control genes at post-transcriptional level. They are essential for development and tissue differentiation, and such altered miRNA expression patterns are linked to the pathogenesis of inflammation and cancer. There is evidence that miRNA expression is genetically controlled similar to the transcription of protein coding genes and previous studies identified quantitative trait loci (QTL) for miRNA expression in the liver. So far, little attention has been paid to miRNA expression in the skin. Moreover, epistatic control of miRNA expression remains unknown. In this study, we characterize genetic regulation of cutaneous miRNA and their correlation with skin inflammation using a previously established murine autoimmune-prone advanced intercross line. RESULTS: We identified in silico 42 eQTL controlling the expression of 38 cutaneous miRNAs and furthermore found two chromosomal hot-spots on chromosomes 2 and 8 that control the expression of multiple miRNAs. Moreover, for 8 miRNAs an interacting effect from pairs of SNPs was observed. Combining the constraints on genes from the statistical interaction of their loci and further using curated protein interaction networks, the number of candidate genes for association of miRNAs was reduced to a set of several genes. A cluster analysis identified miR-379 and miR-223 to be associated with EBA severity/onset, where miR-379 was observed to be associated to loci on chromosome 6. CONCLUSION: The murine advanced intercross line allowed us to identify the genetic loci regulating multiple miRNA in skin. The recurrence of trans-eQTL and epistasis suggest that cutaneous miRNAs are regulated by yet an unexplored complex gene networks. Further, using co-expression analysis of miRNA expression levels we showed that multiple miRNA contribute to multiple pathways that might be involved in pathogenesis of autoimmune skin blistering disease. Specifically, we provide evidence that miRNA such as miR-223 and miR-379 may play critical role in disease progression and severity. PMID- 26879239 TI - An orthostatic hypotension mimic: The inebriation-like syndrome in Parkinson disease. PMID- 26879238 TI - Recurrent laryngeal nerve recovery patterns assessed by serial electromyography. AB - OBJECTIVES/HYPOTHESIS: Following acute injury to the recurrent laryngeal nerve (RLN), laryngeal electromyography (LEMG) is increasingly being used to determine prognosis for recovery. The LEMG findings change during the recovery process, but the timing of these changes is not well described. In this canine study, LEMGs were obtained serially following model RLN injuries. STUDY DESIGN: Animal Study. METHODS: Thirty-six canine RLNs underwent crush (n = 6), complete transection with reanastomosis (n = 6), half-transection half-crush (n = 5), cautery (n = 5), stretch (n = 5), inferior crush (n = 4), or inferior transection with reanastomosis (n = 5) injuries. Injuries were performed 5 cm from cricoid or were 5 cm further inferior. Under light sedation, LEMG of thyroarytenoid muscles was performed monthly for 6 months following injury. At 6 months, spontaneous and induced vocal fold motion was assessed. RESULTS: Except for the stretch injury, the remaining groups showed very similar recovery patterns. Fibrillation potentials (FPs) and/or positive sharp waves (PSWs; signs of bad prognosis) were seen in all cases at 1 month and lasted on average for 2.26 months (range = 1-4 months). Motor unit potentials of at least 2+ (scale = 0-4+; signs of good prognosis) were seen beginning at 3.61 months (range = 2-6 months). The stretch injury was less severe, with 3 of 5 showing no FPs/PSWs at 1 month; all recovered full mobility. Ten of the 36 thyroarytenoid muscles (27.8%) had 1 electromyograph showing both bad prognosis and good prognosis signs simultaneously at 2 to 4 months postinjury. CONCLUSIONS: LEMG can be used to predict RNL recovery, but timing is important and LEMG results earlier than 3 months may overestimate a negative prognosis. LEVEL OF EVIDENCE: NA Laryngoscope, 126:651-656, 2016. PMID- 26879240 TI - Early beta-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy. AB - OBJECTIVE: A catecholamine-mediated mechanism has been implicated in the pathogenesis of Takotsubo cardiomyopathy (TC). However, the impact of beta blockers in acute-phase management of TC remains uncertain. This study aimed to examine whether early beta-blocker use in TC was associated with lower in hospital mortality. METHODS: This was a retrospective cohort study using the Diagnosis Procedure Combination nationwide inpatient database in Japan. Patients with TC aged >=20 years who were admitted to acute-care hospitals between 2010 and 2014 were identified. Thirty-day in-hospital mortality was compared between patients who started beta-blocker therapy on hospitalisation day 1 or 2 (early beta-blocker group) and those who did not receive a beta-blocker during hospitalisation (control group) using propensity score-matching and instrumental variable analyses. RESULTS: Of 2672 eligible patients (female, 81.5%; 423 early beta-blocker therapy, 2249 controls) from 615 hospitals, 1:4 propensity score matching created a cohort of 2110 patients (422 early beta-blocker therapy, 1688 controls). There was no significant difference in 30-day in-hospital mortality between the early beta-blocker group and control group (2.4% vs 2.0%, p=0.703; risk difference, 0.4%; 95% CI, -1.2% to 2.0%). Logistic regression analysis did not show a significant association between early beta-blocker use and 30-day in hospital mortality (OR, 1.17; 95% CI 0.58 to 2.37). Instrumental variable analysis also found that early beta-blocker use was not associated with lower 30 day in-hospital mortality (risk difference, 1.2%; 95% CI -3.1% to 5.5%). CONCLUSIONS: This study found no significant association between early beta blocker use and in-hospital mortality in patients with TC. PMID- 26879241 TI - Prolonged PR interval, first-degree heart block and adverse cardiovascular outcomes: a systematic review and meta-analysis. AB - OBJECTIVE: First-degree atrioventricular block is frequently encountered in clinical practice and is generally considered a benign process. However, there is emerging evidence that prolonged PR interval may be associated with adverse outcomes. This study aims to determine if prolonged PR interval is associated with adverse cardiovascular outcomes and mortality. METHODS: We searched MEDLINE and EMBASE for studies that evaluated clinical outcomes associated with prolonged and normal PR intervals. Relevant studies were pooled using random effects meta analysis for risk of mortality, cardiovascular mortality, heart failure, coronary heart disease, atrial fibrillation and stroke or transient ischaemic attack (TIA). Sensitivity analyses were performed considering the population type and the use of adjustments. RESULTS: Our search yielded 14 studies that were undertaken between 1972 and 2011 with 400,750 participants. Among the studies that adjusted for potential confounders, the pooled results suggest an increased risk of mortality with prolonged PR interval risk ratio (RR) 1.24 95% CI 1.02 to 1.51, five studies. Prolonged PR interval was associated with significant risk of heart failure or left ventricular dysfunction (RR 1.39 95% CI 1.18 to 1.65, three studies) and atrial fibrillation (RR 1.45 95% CI 1.23 to 1.71, eight studies) but not cardiovascular mortality, coronary heart disease or myocardial infarction or stroke or TIA. Similar observations were recorded when limited to studies of first-degree heart block. CONCLUSIONS: Data from observational studies suggests a possible association between prolonged PR interval and significant increases in atrial fibrillation, heart failure and mortality. Future prospective studies are needed to confirm the relationships reported, consider possible mechanisms and define the optimal monitoring strategy for such patients. PMID- 26879243 TI - Heteroleptic Tetrapyrrole-Fused Dimeric and Trimeric Skeletons with Unusual Non Frustrated Fluorescence. AB - Phthalocyanine (Pc) and porphyrin (Por) chromophores have been fused through the benzo[alpha]pyrazine moiety, resulting in unprecedented heteroleptic tetrapyrrole fused dimers and trimers. The heteroleptic tetrapyrrole nature has been clearly revealed based on single-crystal X-ray diffraction analysis of the zinc dimer. Electrochemical analysis, theoretical calculations, and time-resolved spectroscopic results disclose that the two/three-tetrapyrrole-fused skeletons behave as one totally pi-conjugated system as a result of the strong conjugative interaction between/among the tetrapyrrole chromophores. In particular, the effectively extended pi-electron system through the fused-bridge induced strong electronic communication between the Pc and Por moieties and large transition dipole moments in the Pc-Por-fused systems, providing high fluorescence quantum yields (>0.13) and relatively long excited state lifetimes (>1.3 ns) in comparison with their homo-tetrapyrrole-fused analogues. PMID- 26879242 TI - Monitoring the biological activity of abdominal aortic aneurysms Beyond Ultrasound. AB - Abdominal aortic aneurysms (AAAs) are an important cause of morbidity and, when ruptured, are associated with >80% mortality. Current management decisions are based on assessment of aneurysm diameter by abdominal ultrasound. However, AAA growth is non-linear and rupture can occur at small diameters or may never occur in those with large AAAs. There is a need to develop better imaging biomarkers that can identify the potential risk of rupture independent of the aneurysm diameter. Key pathobiological processes of AAA progression and rupture include neovascularisation, necrotic inflammation, microcalcification and proteolytic degradation of the extracellular matrix. These processes represent key targets for emerging imaging techniques and may confer an increased risk of expansion or rupture over and above the known patient-related risk factors. Magnetic resonance imaging, using ultrasmall superparamagnetic particles of iron oxide, can identify and track hotspots of macrophage activity. Positron emission tomography, using a variety of targeted tracers, can detect areas of inflammation, angiogenesis, hypoxia and microcalcification. By going beyond the simple monitoring of diameter expansion using ultrasound, these cellular and molecular imaging techniques may have the potential to allow improved prediction of expansion or rupture and to better guide elective surgical intervention. PMID- 26879244 TI - Interfacial Engineering for Quantum-Dot-Sensitized Solar Cells. AB - Quantum-dot-sensitized solar cells (QDSCs) are promising solar-energy-conversion devices, as low-cost alternatives to the prevailing photovoltaic technologies. Compared with molecular dyes, nanocrystalline quantum dot (QD) light absorbers exhibit higher molar extinction coefficients and a tunable photoresponse. However, the power-conversion efficiencies (PCEs) of QDSCs are generally below 9.5 %, far behind their molecular sensitizer counterparts (up to 13 %). These low PCEs have been attributed to a large free-energy loss during sensitizer regeneration, energy loss during the charge-carrier transport and transfer processes, and inefficient charge separation at the QD/electrolyte interfaces, and various interfacial engineering strategies for enhancing the PCE and cell stability have been reported. Herein, we review recent progress in the interfacial engineering of QDSCs and discuss future prospects for the development of highly efficient and stable QDSCs. PMID- 26879246 TI - The effects of different types of hair shaving on the body image and surgical site infection in elective cranial surgery. AB - AIMS AND OBJECTIVES: To investigate the effects of different types of shaving on body image and surgical site infection in elective cranial surgery. BACKGROUND: Hair shaving before cranial surgery is commonly performed in many countries. However, the impact of shaving on the patients' body image and surgical site infection is not, as yet, well investigated. DESIGN: A randomised-controlled design was used in this study. METHODS: The sample comprised 200 patients who underwent elective cranial surgery between March 2013-August 2014. The Center for Disease Control and Prevention criteria were applied for the preoperative preparation of patients and for the follow-up of surgical site infection. Wound swab cultures were obtained four times from all patients. The Social Appearance Anxiety Scale was used to assess changes in the body image of patients. FINDINGS: The rate of surgical site infection was 1% for each group and for all patients. There was no difference between the groups of surgical site infection. Coagulase negative staphylococci and Staphylococcus epidermidis were mostly isolated in the swab cultures. The Social Appearance Anxiety Scale score decreased in patients who underwent strip shaving and increased in patients with regional shaving. CONCLUSION: There is no difference between strip shaving and regional shaving in the development of surgical site infection after cranial surgery. In addition, regional hair shaving negatively affects the patients' body image. RELEVANCE TO CLINICAL PRACTICE: Findings of this study provide useful evidence-based information for healthcare professionals. The development and implementation of effective interventions result in the prevention of surgical site infection and improvement of the patients' body image in elective cranial surgery. PMID- 26879245 TI - Anti-c-Met monoclonal antibody ABT-700 breaks oncogene addiction in tumors with MET amplification. AB - BACKGROUND: c-Met is the receptor tyrosine kinase for hepatocyte growth factor (HGF) encoded by the MET proto-oncogene. Aberrant activation of c-Met resulting from MET amplification and c-Met overexpression is associated with poor clinical outcome in multiple malignancies underscoring the importance of c-Met signaling in cancer progression. Several c-Met inhibitors have advanced to the clinic; however, the development of inhibitory c-Met-directed therapeutic antibodies has been hampered by inherent agonistic activity. METHOD: We generated and tested a bivalent anti-c-Met monoclonal antibody ABT-700 in vitro for binding potency and antagonistic activity and in vivo for antitumor efficacy in human tumor xenografts. Human cancer cell lines and gastric cancer tissue microarrays were examined for MET amplification by fluorescence in situ hybridization (FISH). RESULTS: ABT-700 exhibits a distinctive ability to block both HGF-independent constitutive c-Met signaling and HGF-dependent activation of c-Met. Cancer cells addicted to the constitutively activated c-Met signaling driven by MET amplification undergo apoptosis upon exposure to ABT-700. ABT-700 induces tumor regression and tumor growth delay in preclinical tumor models of gastric and lung cancers harboring amplified MET. ABT-700 in combination with chemotherapeutics also shows additive antitumor effect. Amplification of MET in human cancer tissues can be identified by FISH. CONCLUSIONS: The preclinical attributes of ABT 700 in blocking c-Met signaling, inducing apoptosis and suppressing tumor growth in cancers with amplified MET provide rationale for examining its potential clinical utility for the treatment of cancers harboring MET amplification. PMID- 26879248 TI - Evolution of rapid nerve conduction. AB - Rapid conduction of nerve impulses is a priority for organisms needing to react quickly to events in their environment. While myelin may be viewed as the crowning innovation bringing about rapid conduction, the evolution of rapid communication mechanisms, including those refined and enhanced in the evolution of myelin, has much deeper roots. In this review, a sequence is traced starting with diffusional communication, followed by transport-facilitated communication, the rise of electrical signaling modalities, the invention of voltage-gated channels and "all-or-none" impulses, the emergence of elongate nerve axons specialized for communication and their fine-tuning to enhance impulse conduction speeds. Finally within the evolution of myelin itself, several innovations have arisen and have been interactively refined for speed enhancement, including the addition and sealing of layers, their limitation by space availability, and the optimization of key parameters: channel density, lengths of exposed nodes and lengths of internodes. We finish by suggesting several design principles that appear to govern the evolution of rapid conduction. This article is part of a Special Issue entitled SI: Myelin Evolution. PMID- 26879247 TI - Hidden musculoskeletal involvement in inflammatory bowel disease: a multicenter ultrasound study. AB - BACKGROUND: Inflammatory bowel diseases are associated with a variety of extra intestinal manifestations. The most frequent of these is joint involvement, which affects 16-33 % of IBD patients. Our aim was to evaluate the ultrasound prevalence of sub-clinical joint and entheseal involvement in patients with IBD without musculoskeletal symptoms, and to correlate the US findings with clinical and laboratory variables. METHODS: We recorded the clinical and laboratory data of 76 patients with IBD, 20 patients with spondyloarthritis (SpA) and 45 healthy controls at three rheumatology centers. All of the IBD patients and healthy controls were clinically examined by a rheumatologist in order to confirm the absence of musculoskeletal symptoms, and all of the subjects underwent grey-scale (GS) and power Doppler (PD) US examinations of the second and third metacarpophalangeal joints, knees and lower limbs in order to detect joint or entheseal abnormalities. RESULTS: A total of 1410 entheseal sites and 1410 joints were evaluated by US. Of the 76 patients with IBD, 64 (84.1 %) had at least one GS entheseal abnormality, and 11 (13.9 %) had more than one PD-positive entheseal site; 32 (42.1 %) showed sub-clinical joint involvement. There was a significant difference between the IBD patients and healthy controls in terms of global entheseal, PD-positive entheseal, and joint involvement (p < 0.0001), but no difference between the IBD and SpA patients. Anti-neutrophil cytoplasmic antibodies predicted entheseal involvement in patients with IBD (OR 6.031; p = 0.015). CONCLUSIONS: The prevalence of sub-clinical joint and entheseal involvement was higher in IBD patients than healthy controls, but there was no difference between the IBD and SpA patients. PMID- 26879249 TI - Local electron-electron interaction strength in ferromagnetic nickel determined by spin-polarized positron annihilation. AB - We employ a positron annihilation technique, the spin-polarized two-dimensional angular correlation of annihilation radiation (2D-ACAR), to measure the spin difference spectra of ferromagnetic nickel. The experimental data are compared with the theoretical results obtained within a combination of the local spin density approximation (LSDA) and the many-body dynamical mean-field theory (DMFT). We find that the self-energy defining the electronic correlations in Ni leads to anisotropic contributions to the momentum distribution. By direct comparison of the theoretical and experimental results we determine the strength of the local electronic interaction U in ferromagnetic Ni as 2.0 +/- 0.1 eV. PMID- 26879250 TI - Selective Pyroelectric Detection of Millimetre Waves Using Ultra-Thin Metasurface Absorbers. AB - Sensing infrared radiation is done inexpensively with pyroelectric detectors that generate a temporary voltage when they are heated by the incident infrared radiation. Unfortunately the performance of these detectors deteriorates for longer wavelengths, leaving the detection of, for instance, millimetre-wave radiation to expensive approaches. We propose here a simple and effective method to enhance pyroelectric detection of the millimetre-wave radiation by combining a compact commercial infrared pyro-sensor with a metasurface-enabled ultra-thin absorber, which provides spectrally- and polarization-discriminated response and is 136 times thinner than the operating wavelength. It is demonstrated that, due to the small thickness and therefore the thermal capacity of the absorber, the detector keeps the high response speed and sensitivity to millimetre waves as the original infrared pyro-sensor does against the regime of infrared detection. An in-depth electromagnetic analysis of the ultra-thin resonant absorbers along with their complex characterization by a BWO-spectroscopy technique is presented. Built upon this initial study, integrated metasurface absorber pyroelectric sensors are implemented and tested experimentally, showing high sensitivity and very fast response to millimetre-wave radiation. The proposed approach paves the way for creating highly-efficient inexpensive compact sensors for spectro polarimetric applications in the millimetre-wave and terahertz bands. PMID- 26879251 TI - [Editorial]. PMID- 26879252 TI - [Pharmacological properties of vortioxetine and its pre-clinical consequences]. AB - Selective Serotonin Reuptake Inhibitors (SSRIs) are extensively used for the treatment of major depressive disorder (MDD). SSRIs are defined as indirect receptor agonists since the activation of postsynaptic receptors is a consequence of an increase in extracellular concentrations of serotonin (5-HT) mediated by the blockade of serotonin transporter. The activation of some serotoninergic receptors (5-HT1A, post-synaptic, 5-HT1B post-synaptic, 5-HT2B, and 5-HT4), but not all (5-HT1A, pre-synaptic, 5-HT1B pre-synaptic, 5-HT2A, 5-HT2C, 5-HT3, and probably 5-HT6), induces anxiolytic/antidepressive - like effects. Targetting specifically some of them could potentially improve the onset of action and/or efficacy and/or prevent MD relapse. Vortioxetine (Brintellix, 1- [2-(2,4 dimethylphenyl-sulfanyl)-phenyl]-piperazine) is a novel multi-target antidepressant drug approved by the Food and Drug Administration (FDA) and by European Medicines Agency. Its properties are markedly different from the extensively prescribed SSRIs. Compared to the SSRIs, vortioxetine is defined as a multimodal antidepressant drug since it is not only a serotonin reuptake inhibitor, but also a 5-HT1D, 5-HT3, 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist and 5-HT1A receptor agonist. This specific pharmacological profile enables vortioxetine to affect not only the serotoninergic and noradrenergic systems, but also the histaminergic, cholinergic, gamma-butyric acid (GABA) ergic and glutamatergic ones. Thus, vortioxetine not only induces antidepressant-like or anxiolytic-like activity but also improves cognitive parameters in several animal models. Indeed, vortioxetine was shown to improve working memory, episodic memory, cognitive flexibility and spatial memory in young adult rodents and also in old animal models. These specific effects of the vortioxetine are of interest considering that cognitive dysfunction is a common comorbidity to MDD. Altogether, even though this molecule still needs to be investigated further, especially in the insufficient-response to antidepressant drugs, vortioxetine is already an innovative therapeutic option for the treatment of major depression. PMID- 26879253 TI - [Placebo effect: clinical, biological and therapeutical involvements in depression]. AB - The placebo effect is an excellent model for understanding the mechanisms underlying the interaction between a subjective and complex mental activity (beliefs, expectations, hopes, learning, patient-physician relationship, socio cultural context .) with different neural and biological systems. Initially, research on the placebo effect has focused on the mechanisms of pain and analgesia. The cognitive processes of conditioning and reward anticipation (hope of a relief) were highlighted. The involvement of different neurobiological pathways has been clearly shown: endogenous opioids, CCK, dopaminergic pathways, endocannabinoids, immunological factors... More recently, the field has open towards new perspectives: depression and anxiety, motor disorders, immune system, endocrine system. Intensive research in the field emerges because of its fundamental implications in neuroscience research but also because of the ethical, clinical and therapeutical issues. Moreover, the placebo effect is considered as a main methodological mean issue in clinical trials that allows the demonstration of the efficacy and tolerance of new drugs. In the field of psychiatry, depression is a placebo highly-sensitive disorder: placebo response rates in clinical trials are of the order of 30 % to 40 %. The identification of biological markers of placebo response, such as neuroimaging and quantitative electroencephalography may lead to develop more efficient models in clinical research. PMID- 26879254 TI - [Cognition - the core of major depressive disorder]. AB - Cognitive deficits have been only recently recognized as a major phenotype determinant of major depressive disorder, although they are an integral part of the definition of the depressive state. Congruent evidence suggest that these cognitive deficits persist beyond the acute phase and may be identified at all ages. The aim of the current study was to review the main meta-analyses on cognition and depression, which encompasses a large range of cognitive domains. Therefore, we discuss the "cold" (attention, memory, executive functions) and "hot" (emotional bias) cognitive impairments in MDD, as well as those of social cognition domains (empathy, theory of mind). Several factors interfere with cognition in MDD such as clinical (melancholic, psychotic...) features, age, age of onset, illness severity, medication and comorbid condition. As still debated in the literature, the type of relationship between the severity of cognitive symptoms and functioning in depression is detailed, thus highlighting their predictive value of functional outcome, independently of the affective symptoms. A better identification of the cognitive deficits in MDD and a monitoring of the effects of different treatments require appropriate instruments, which may be developed by taking advantage of the increasing success of computing tools. Overall, current data suggest a core role for different cognitive deficits in MDD, therefore opening new perspectives for optimizing the treatment of depression. PMID- 26879255 TI - [Unsatisfactory response: definition and involvement]. AB - In the treatment of unipolar depression, treatment response is a key issue in terms of evolution and prognosis. Within this concept, the inadequate response includes the worsening, the lack of response, partial response and poor tolerance. This lack of response may be related to intrinsic factors to the individual, but also to more extrinsic environmental factors. In this review, we explore this concept through its links with adherence and treatment duration. In this field, the concept of early response can be a powerful indicator of therapeutic response, which conditions the prescription of antidepressants beyond the strict framework of the sufficient period of 4 to 6 weeks. In addition to its impact on prognosis, the literature data show that the insufficient response is a significant burden in terms of medical and economic cost, and somatic comorbidity; and justifies a systematic identification of this dimension. Therefore self-reports (QIDS; BDI) will be preferred to the clinician-rated depression symptom rating scales (MADRS, HAMD) that require a specific training. Identifying predictors of non-response would be an attractive target for prescribers but the results to date are not operative. PMID- 26879256 TI - [How to treat and manage unsatisfactory response?]. AB - Only one third of patients suffering from depression will achieve a satisfactory response with first line treatments and more than half of patients will fail to obtain at least 50 % reduction in their symptoms after 3 months of treatment. This article presents a review of the scientific arguments supporting the various therapeutic strategies when confronted to a first treatment failure after an adequate drug trial. Several pharmacological approaches are possible. A first and classical approach is adjusting the drug dosage (optimization). This strategy is coherent with the pharmacological profile of some antidepressant drugs (tricyclic antidepressants, tetracyclic antidepressants, venlafaxine). There is no scientific basis to a dose-effect relationship with the selective serotonin reuptake inhibitors (SSRIs), as minimal doses of these drugs correspond to a high ratio of serotonin transporter occupation; however increasing doses of SSRIs constitutes a usual practice, endorsed by several experts. A second classic strategy is changing an inefficient antidepressant drug to another antidepressant drug (switch). Theoretically, a different pharmacological class should have more chances to be successful; however, in the case of a failure with an SSRI, an inter-class switch has not consistently proven to be superior to an intra-class switch. In some cases, association of antidepressant drugs can also be an advantageous strategy (combination), particularly in the case of partial response with the first prescribed drug. Due to its particular mechanism of action, mirtazapine is often a drug of choice in the case of such an association. Finally, another approach to recommend in case of partial response is associating an antidepressant drug to another class of drugs, such as lithium, atypical antipsychotics or thyroid hormones (potentiation). Lithium has unfailingly proven its efficacy in case of resistance, but the utilization of atypical antipsychotics, at low-doses, has become increasingly common, certainly, because they are easier to handle. Aside from the pharmacological options, we can consider a number of other strategies, first among them is psychotherapy. Most studies assessing the efficacy of psychotherapy were conducted with this therapy as a first-line treatment. More studies of psychotherapy in depression after unsatisfactory response are distinctly needed. Available data seem to indicate that psychotherapy constitutes an efficient alternative, regardless of the type of psychotherapy (results are more robust in cognitive and behavioural therapies and brief interpersonal psychotherapy, in relation with the greater number of studies using these therapies), with effect sizes comparable to the ones obtained with pharmacological options. Among other strategies, physical exercise has been getting more attention lately, even though evidence in this indication remains deceiving for the moment. Lastly, neuromodulation techniques have an unquestionable place. The rTMS has been largely tested with interesting results. Given the time and staff necessary to conduct this therapy, the question has now switched to how precisely select the patients who will most benefit from rTMs, and how long and at what pace should the sessions take place. ECT is undoubtedly the most efficient treatment, but, apart from life-threatening melancholia and other restricted exceptions, it is usually indicated in multi-resistant depression. Some authors suggest using this therapy earlier, as chronicity of the disease is itself a factor of poor response. Finally, this article reviews also the most recent French and International guidelines in managing patients having showed an unsatisfactory response to a first-line treatment. PMID- 26879257 TI - Thermal and quantum depletion of superconductivity in narrow junctions created by controlled electromigration. AB - Superconducting nanowires currently attract great interest due to their application in single-photon detectors and quantum-computing circuits. In this context, it is of fundamental importance to understand the detrimental fluctuations of the superconducting order parameter as the wire width shrinks. In this paper, we use controlled electromigration to narrow down aluminium nanoconstrictions. We demonstrate that a transition from thermally assisted phase slips to quantum phase slips takes place when the cross section becomes less than ~150 nm(2). In the regime dominated by quantum phase slips the nanowire loses its capacity to carry current without dissipation, even at the lowest possible temperature. We also show that the constrictions exhibit a negative magnetoresistance at low-magnetic fields, which can be attributed to the suppression of superconductivity in the contact leads. These findings reveal perspectives of the proposed fabrication method for exploring various fascinating superconducting phenomena in atomic-size contacts. PMID- 26879259 TI - Metastable Nitric Acid Trihydrate in Ice Clouds. AB - The composition of high-altitude ice clouds is still a matter of intense discussion. The constituents in question are ice and nitric acid hydrates, but the exact phase composition of clouds and its formation mechanisms are still unknown. In this work, conclusive evidence for a long-predicted phase, alpha nitric acid trihydrate (alpha-NAT), is presented. This phase was characterized by a combination of X-ray and neutron diffraction experiments, allowing a convincing structure solution. Furthermore, vibrational spectra (infrared and inelastic neutron scattering) were recorded and compared with theoretical calculations. A strong interaction between water ice and alpha-NAT was found, which explains the experimental spectra and the phase-transition kinetics. On the basis of these results, we propose a new three-step mechanism for NAT formation in high-altitude ice clouds. PMID- 26879258 TI - A single residue substitution accounts for the significant difference in thermostability between two isoforms of human cytosolic creatine kinase. AB - Creatine kinase (CK) helps maintain homeostasis of intracellular ATP level by catalyzing the reversible phosphotransfer between ATP and phosphocreatine. In humans, there are two cytosolic CK isoforms, the muscle-type (M) and the brain type (B), which frequently function as homodimers (hMMCK and hBBCK). Interestingly, these isoenzymes exhibit significantly different thermostabilities, despite high similarity in amino acid sequences and tertiary structures. In order to investigate the mechanism of this phenomenon, in this work, we first used domain swapping and site-directed mutagenesis to search for the key residues responsible for the isoenzyme-specific thermostability. Strikingly, the difference in thermostability was found to principally arise from one single residue substitution at position 36 (Pro in hBBCK vs. Leu in hMMCK). We then engaged the molecular dynamics simulations to study the molecular mechanism. The calculations imply that the P36L substitution introduces additional local interactions around residue 36 and thus further stabilizes the dimer interface through a complex interaction network, which rationalizes the observation that hMMCK is more resistant to thermal inactivation than hBBCK. We finally confirmed this molecular explanation through thermal inactivation assays on Asp36 mutants that were proposed to devastate the local interactions and thus the dimer associations in both isoenzymes. PMID- 26879260 TI - Enhancing performance and uniformity of CH3NH3PbI(3-x)Cl(x) perovskite solar cells by air-heated-oven assisted annealing under various humidities. AB - To fabricate high-performance metal-halide perovskite solar cells, a thermal annealing process is indispensable in preparing high quality perovskite film. And usually such annealing is performed on hot plate. However hot-plate annealing could cause problems such as inhomogeneous heating (induced by non-tight contact between the sample and the plate), it is also not fit for large scale manufactory. In this paper, we conduct the annealing process in air-heated oven under various humidity environments, and compared the resulted films (CH3NH3PbI(3 x)Cl(x)) and devices (Al/PC61BM/CH3NH3PbI(3-x)Cl(x)/ PEDOT: PSS/ITO/glass) with that obtained via hot-plate annealing. It is found that the air-heated-oven annealing is superior to the hot-plate annealing: the annealing time is shorter, the films are more uniform, and the devices exhibit higher power conversion efficiency and better uniformity. The highest efficiencies achieved for the oven and hot-plate annealing processes are 14.9% and 13.5%, and the corresponding standard deviations are 0.5% and 0.8%, respectively. Our work here indicates that air-heated-oven annealing could be a more reliable and more efficient way for both lab research and large-scale production. PMID- 26879261 TI - Is leukocyte tissue factor the key to venous thrombosis in antiphospholipid syndrome? PMID- 26879264 TI - Genetic analysis of NCSTN for potential association with hidradenitis suppurativa in familial and nonfamilial patients. PMID- 26879262 TI - Chemical control of xylem differentiation by thermospermine, xylemin, and auxin. AB - The xylem conducts water and minerals from the root to the shoot and provides mechanical strength to the plant body. The vascular precursor cells of the procambium differentiate to form continuous vascular strands, from which xylem and phloem cells are generated in the proper spatiotemporal pattern. Procambium formation and xylem differentiation are directed by auxin. In angiosperms, thermospermine, a structural isomer of spermine, suppresses xylem differentiation by limiting auxin signalling. However, the process of auxin-inducible xylem differentiation has not been fully elucidated and remains difficult to manipulate. Here, we found that an antagonist of spermidine can act as an inhibitor of thermospermine biosynthesis and results in excessive xylem differentiation, which is a phenocopy of a thermospermine-deficient mutant acaulis5 in Arabidopsis thaliana. We named this compound xylemin owing to its xylem-inducing effect. Application of a combination of xylemin and thermospermine to wild-type seedlings negates the effect of xylemin, whereas co-treatment with xylemin and a synthetic proauxin, which undergoes hydrolysis to release active auxin, has a synergistic inductive effect on xylem differentiation. Thus, xylemin may serve as a useful transformative chemical tool not only for the study of thermospermine function in various plant species but also for the control of xylem induction and woody biomass production. PMID- 26879265 TI - Molecular mechanism of constitutively active Rab11A was revealed by crystal structure of Rab11A S20V. AB - Rab11A is a small GTP-binding protein involved in the regulation of vesicle trafficking during recycling of endosomes. Substitution of S20 to V (S20V) at Rab11A inhibits the GTP hydrolysis activity of Rab11A. This mutation is known to be constitutively in an active form. Here, we report the crystal structure of the human Rab11A S20V mutant form complexed with GTP at a resolution of 2.4 A. Without adding any substrate, Rab11A contained non-hydrolyzed natural substrate GTP in the nucleotide binding pocket with Mg(2+). In our observations, substituted V20 of Rab11A was found to interfere with proper localization of the water molecule, which mediated GTP hydrolysis, resulting in GTP being locked in an active form of Rab11A S20V. PMID- 26879266 TI - Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency. AB - INTRODUCTION: Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics (PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pdFX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. AIM: This analysis assessed pdFX PK after a single 25 IU kg(-1) bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [FX:C] <5 IU dL(-1) ). METHODS: For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After >=6 months of on-demand pdFX treatment and treatment of >=1 bleed with pdFX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen. RESULTS: FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline (n = 16) and repeat (n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits (n = 31). The mean terminal half-life and incremental recovery of pdFX was 29.4 h and 2.00 IU dL(-1) per IU kg(-1) respectively. CONCLUSION: This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy. PMID- 26879267 TI - Multifactorial etiology of Torus mandibularis: study of twins. AB - OBJECTIVE: The aim of this study is to investigate the multifactorial etiology of mandibular tori analyzing the influence of genetics, occlusal overload, various clinical variables and their interactions. METHODS: Overall, plaster casts of 162 twins (81 twin pairs) were analyzed for the presence or absence of mandibular tori. Atypical wear facets on canine tips or incisors were recorded to diagnose bruxism. Angle Class, any kind of anterior open bite and positive, negative or flat curve of Wilson were recorded. Zygosity determination was carried out using a DNA test. RESULTS: Mandibular tori were found in 56.8% of the cases. In 93.6% of all monozygotic twin pairs both individuals had or did not have mandibular tori (kappa=0.96+/-0.04; p<0.001), compared to 79.4% concordance of mandibular tori in dizygotic co-twins (kappa=0.7+/-0.12; p<0.001). Prevalence of mandibular tori was significantly higher in the group of bruxers (67.5%) compared to non bruxers (31.3%) (p<0.001). Significant association between mandibular tori and negative or flat curve of Wilson in the maxillary second premolars and first molars was found (OR=2.55, 95% CI (1.19-5.46), p=0.016). In all monozygotic bruxers, 97.1% showed concordance of mandibular tori presence in both co-twins compared to 78.9% dizygotic bruxers, and this difference is statistically significant (p=0.007). CONCLUSION: Our results suggest that the mandibular tori are of a multifactorial origin. Mandibular tori seem to have genetic predisposition, and may be associated with teeth grinding as well as with negative or flat CW in region of maxillary second premolar and first molar. PMID- 26879268 TI - The relationship between mandibular rotation and osseous structure of the TMJ in pre-surgery orthognathic patients: A cone beam CT study. AB - The aim of the study was to assess the relationship between vertical skeletal pattern in terms of mandibular rotation and osseous structural changes of the TMJ in pre- surgical orthognatic patients. TMJ skeletal morphology was evaluated in cone beam computer tomography images of 117 consecutive patients with Class II and Class III dentofacial deformities according to the research diagnostic criteria of the osseous components of the TMJ related to the maxillary-mandibular plane (MM) angle. The distribution of the number and percentage of joints with structural changes in Class II was markedly different in groups divided according to the MM angle. Statistically significant increase was found in the percentage of TMJ's with osseous changes separately for each side, i.e., right (p=0.001), left (p=0.04) and both together (p=0.0001), in the Class II patient group, an increased MM angle indicated backward rotation of the mandible. In Class III patients, there were no statistically significant differences in the number of joints with TMJ structural changes. The presence of mentioned changes was asymmetrical between the left and right joints in both the Class II and Class III patient groups. In conclusion, structural changes in the osseous parts of the TMJ are more common in patients with Class II skeletal dentofacial deformities with backward rotation of the mandible than in Class III pre-surgery orthognathic patients. PMID- 26879269 TI - Oral health related to quality of life in patients with stomatological diseases. AB - AIM: To describe the oral health-related quality of life (OHR-QoL) in patients with stomatological diseases. METHODS: All new patients seen in the Stomatology Clinic, from August 2008 to July 2009 were selected. OHR-QoL was measured using OHIP-14, in face-to-face interviews. The stomatological diseases were classified into groups according to their origin. OHIP-14 data were used to calculate two variables: prevalence and severity. RESULTS: The questionnaire was completed by 113 subjects, with a mean of 53.77 years; 63.7% women; 38% of the subjects reported one or more OHR-QoL impacts "fairly often" or "very often" in the last 6 months. The overall result of OHIP-14 index showed a mean of 14.35 (+/-12.01). There was no statistical significance between the stomatological disease groups and the prevalence scores (p=0.25) and mean severity scores (p=0.57). CONCLUSIONS: It seems that bad oral conditions affected quality of life of these patients, especially physical pain and psychological discomfort. PMID- 26879270 TI - Candida albicans importance to denture wearers. A literature review. AB - Opportunistic oral fungal infections have spred, especially in denture wearers. Denture stomatitis is a common inflammatory reaction, multifactorial etiology, which is usually associated with Candida species, particularly Candida albicans, due to its high virulence, ability to adhere and form biofilms on oral cavity tissues and denture surfaces. This article highlights the pathogenesis, clinical presentation, and management strategies of Candida-associated denture stomatitis commonly encountered in dental practice. PMID- 26879271 TI - Aspiration and Brushing Cytology in tumors and tumor-like conditions of the tongue: A Study of 27 Cases. AB - BACKGROUND: Lesions of the tongue have a broad differential diagnosis ranging from benign idiopathic processes to infections, cancers, and infiltrative disorders. An important thing to remember is that most tongue lesions will resolve spontaneously or with simple therapy within a week, if not, they should be biopsied or evaluated further for a definitive diagnosis of a potentially serious disorder. Some tongue lesions may be clues to other underlying illnesses which require further evaluation Tongue lesions are traditionally evaluated by surgical biopsy. Most of them, however, are easily accessible by fine-needle aspiration (FNA) or brushing. STUDY DESIGN: Fifteen males and twelve females aged from 15 to 72 were examined in our institution over a period of 15 years and 27 lesions, were evaluated by fine-needle aspiration cytology (FNAC) or brushing cytology. RESULTS: The lesions were located at the mobile aspect of the tongue.10 malignant tumors were diagnosed: 9 cases of squamous cell carcinoma (SCC), and 1 non-Hodgkin lymphoma (NHL). In addition, 13 benign tumors (7 cases of papillomas / fibromas, 3 cases of hemangiomas, 2 cases lymphangiomas, and 1 case of lipoma), and 4 nonneoplastic benign conditions (3 traumatic ulcers and 1 hematoma) were found. There were no false-positive diagnoses. There were no clinical complications resulting from FNA or brushing. CONCLUSION: Cytologic examination is rapid, safe, accurate, inexpensive, and patient-friendly for establishing preoperative diagnosis in tumors and tumor-like conditions of the tongue, and we recommend this method as the first diagnostic step in the evaluation of these lesions. PMID- 26879272 TI - Low c-Met expression levels are prognostic for and predict the benefits of temozolomide chemotherapy in malignant gliomas. AB - Aberrant c-Met has been implicated in the development of many cancers. The objective of this study was to identify an unfavorable prognostic marker that might guide decisions regarding clinical treatment strategies for high-grade gliomas. C-Met expression was measured using immunohistochemistry in 783 gliomas, and we further analyzed c-Met mRNA levels using the Agilent Whole Genome mRNA Microarray in 286 frozen samples. In vitro, we performed cell migration and invasion assays. Cell sensitivity to temozolomide (TMZ) chemotherapy was determined using MTT assays. Both mRNA and protein levels of c-Met were significantly associated with tumor grade progression and inversely correlated with overall and progression-free survival in high-grade gliomas (all P < 0.0001). These findings were nearly consistent at the mRNA level across 3 independent cohorts. Multivariable analysis indicated that c-Met was an independent prognostic marker after adjusting for age, preoperative Karnofsky Performance Status (KPS) score, the extent of resection, radiotherapy, TMZ chemotherapy, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Further analysis in vitro revealed that downregulating the expression of c-Met dramatically inhibited cell migration and invasion capacities, enhanced sensitivity to TMZ chemotherapy in H4 and U87 glioma cells. Our results suggest that c-Met may serve as a potential predictive maker for clinical decision making. PMID- 26879275 TI - The experiences and needs of individuals with disabilities exposed to chronic political violence. AB - Purpose The main objective of this study was to understand, describe and map the experiences, challenges and needs of individuals with lifelong disabilities, who have been exposed to chronic politically violent events (terror, war or continuous missile attacks) in Israel. Method The study was conducted within the qualitative-constructivist paradigm. Three focus groups consisting of 18 individuals with lifelong disabilities were conducted; each focus group included a specific disability type (physical, visual and hearing impairment). Results The participants reported encountering environmental barriers, such as inaccessibly of the physical environment and information as well as dependency on others. These barriers limited the participants' functioning during emergency period and thus increased their level of distress. The participants also emphasized their physical, social and psychological needs. Conclusions The needs of individuals with disabilities in emergency situations can be met if they have a safe place to stay in, are with someone else, and plan every daily action in advance. It is also imperative to provide accessible services and information. Furthermore, it is recommended to develop training sessions for individuals with disabilities and for service providers regarding how to locate, communicate with and assist individuals with disabilities during security threat situations. Implications for Rehabilitation Successful coping of individuals with lifelong disabilities with chronic politically violent events depends on personal and organizational accommodations. Besides an accessible physical environment, the information provided should be available and accessible through mass media and assistive technologies. A comprehensive emergency service for various disabilities is needed. Service providers should be trained on how to locate, communicate with, and assist individuals with disabilities during security threat situations. PMID- 26879274 TI - Salivary profile in diabetic patients: biochemical and immunological evaluation. AB - BACKGROUND: The aim of this study was to evaluate the biochemical and immunological characteristics of saliva from diabetic patients compared to non diabetic adults. METHODS: Eighty-eight diabetic adults and 39 non-diabetic adults (control) were included in the study. Glucose, urea, calcium, total protein and amylase were determined by a colorimetric method. The levels of secretory IgA and the IgA anti-Streptococcus mutans and anti-insulin IgA antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Caries status was evaluated using the DMFT index. RESULTS: Glucose, urea, calcium, anti-S. mutans IgA, total IgA, and anti-insulin IgA were significantly higher in diabetic patients, whereas total protein and amylase levels were lower in these patients. There was no positive correlation between blood and salivary glucose levels in either group. Diabetic patients had a higher DMFT index. CONCLUSIONS: The present study showed for the first time that IgA levels in diabetic patients'saliva, shows correlation with systemic biochemical parameters. Thus the saliva is an useful tool to follow the systemic health status in these patients. PMID- 26879273 TI - Early changes in cardiovascular structure and function in adolescents with type 1 diabetes. AB - BACKGROUND: Children with type 1 diabetes (T1D) are at higher risk of early adult onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. METHODS AND RESULTS: 199 T1D [14.4 +/- 1.6 years, diabetes duration 6.2 (2.0-12.8) years] and 178 controls (14.4 +/- 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 +/- 10 vs. 110 +/- 9 mmHg; p = 0.0005) and diastolic (62 +/- 7 vs. 58 +/- 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e' (17.6 +/- 2.6 vs. 18.6 +/- 2.6 cm/s; p < 0.001) and a' (5.4 +/- 1.1 vs. 5.9 +/- 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e' (7.3 +/- 1.2 vs. 6.7 +/- 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (-20.4 +/- 2.3 vs. -19.5 +/- 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (-19.0 +/- 1.9 vs. -19.8 +/- 1.5 % p < 0.001) in T1D. CONCLUSIONS: Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions. PMID- 26879277 TI - Ozanimod: a better or just another S1P receptor modulator? PMID- 26879278 TI - AMG 334 CGRP antibody for migraine: time to celebrate? PMID- 26879276 TI - Safety and efficacy of the selective sphingosine 1-phosphate receptor modulator ozanimod in relapsing multiple sclerosis (RADIANCE): a randomised, placebo controlled, phase 2 trial. AB - BACKGROUND: Modulation of sphingosine 1-phosphate (S1P) receptors in a non selective manner decreases disease activity in patients with multiple sclerosis but has potential safety concerns. We assessed the safety and efficacy of the oral selective S1P receptor modulator ozanimod in patients with relapsing multiple sclerosis. METHODS: RADIANCE is a combined phase 2/3 trial. Patients with relapsing multiple sclerosis were recruited from 55 academic and private multiple sclerosis clinics in 13 countries across Europe and the USA. Eligible participants were aged 18-55 years, had an Expanded Disability Status Scale (EDSS) score of 0-5.0, and had either one or more relapses in the previous 12 months, or one or more relapses in the past 24 months and one or more gadolinium enhancing lesions on MRI in the previous 12 months before screening. Participants were assigned by a computer-generated randomisation sequence in a 1:1:1 ratio to ozanimod (0.5 mg or 1 mg) or matching placebo once daily for 24 weeks by an independent, unmasked, statistical team. Trial participants, study site personnel, MRI assessors, steering committee members, and the study statistician were masked to treatment assignment. To attenuate first-dose cardiac effects, ozanimod was up-titrated from 0.25 mg to 0.5 mg or 1 mg over 8 days. The primary endpoint was the cumulative number of total gadolinium-enhancing MRI lesions measured by an independent MRI analysis centre at weeks 12-24 after treatment initiation. Analysis was by intention to treat. Here, we report results from the 24-week phase 2 trial. This trial is registered with ClinicalTrials.gov, number NCT01628393. The 2-year phase 3 trial is ongoing. FINDINGS: The first patient was randomised on Oct 18, 2012, and the final visit of the last randomised patient was on May 11, 2014. The intention-to-treat and safety population consisted of 258 participants, 88 were assigned placebo, 87 ozanimod 0.5 mg, and 83 ozanimod 1 mg; 252 (98%) patients completed the assigned treatment. The mean cumulative number of gadolinium-enhancing lesions at weeks 12-24 was 11.1 (SD 29.9) with placebo compared with 1.5 (3.7) with ozanimod 0.5 mg (odds ratio 0.16, 95% CI 0.08-0.30; p<0.0001) and 1.5 (3.4) with ozanimod 1 mg (odds ratio 0.11, 95% CI 0.06-0.21; p<0.0001). Three serious adverse events unrelated to treatment were reported in patients assigned ozanimod 0.5 mg: optic neuritis, somatoform autonomic dysfunction, and cervical squamous metaplasia (HPV-related). No serious infectious or cardiac adverse events were reported, and no cases of macular oedema arose. The most common adverse events in the ozanimod 0.5 mg and 1 mg groups compared with placebo were nasopharyngitis (11 and five vs 12), headache (five and three vs eight), and urinary-tract infections (six and two vs two). The maximum reduction in mean heart rate by Holter monitoring during the first 6 h in ozanimod-treated participants was less than 2 beats per min (bpm) compared with baseline, with no patient having a minimum hourly heart rate less than 45 bpm. Electrocardiograms and 24-h Holter monitoring showed no increased incidence of atrioventricular block or sinus pause with ozanimod. INTERPRETATION: Ozanimod significantly reduced MRI lesion activity in participants with relapsing multiple sclerosis, with a favourable safety profile over a period of 24 weeks. These findings warrant phase 3 trials, which are ongoing. FUNDING: Receptos, Inc. PMID- 26879279 TI - Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. AB - BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti AMG 334 antibodies. The study is registered with ClinicalTrials.gov, number NCT01952574. An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. FINDINGS: From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was -3.4 (SE 0.4) days with AMG 334 70 mg versus -2.3 (0.3) days with placebo (difference -1.1 days [95% CI -2.1 to -0.2], p=0.021). The mean reductions in monthly migraine days with the 7 mg (-2.2 [SE 0.4]) and the 21 mg (-2.4 [0.4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54%) patients who received placebo, 54 (50%) patients in the AMG 334 7 mg group, 54 (51%) patients in the AMG 334 21 mg group, and 57 (54%) patients in the AMG 334 70 mg group. The most frequently reported adverse events were nasopharyngitis, fatigue, and headache. Serious adverse events were reported for one patient in the AMG 334 7 mg group (ruptured ovarian cyst) and one patient in the AMG 334 70 mg group (migraine and vertigo); these events were judged to be unrelated to AMG 334 treatment. Nine (3%) of 317 patients had neutralising antibodies. No apparent association was recorded between patients with positive anti-AMG 334 antibodies and adverse events. No clinically significant vital signs, laboratory, or electrocardiogram findings were recorded. INTERPRETATION: These results suggest that AMG 334 70 mg might be a potential therapy for migraine prevention in patients with episodic migraine and support further investigation of AMG 334 in larger phase 3 trials. FUNDING: Amgen. PMID- 26879280 TI - Recording and analysis of head movements, interaural level and time differences in rooms and real-world listening scenarios. AB - The science of how we use interaural differences to localise sounds has been studied for over a century and in many ways is well understood. But in many of these psychophysical experiments listeners are required to keep their head still, as head movements cause changes in interaural level and time differences (ILD and ITD respectively). But a fixed head is unrealistic. Here we report an analysis of the actual ILDs and ITDs that occur as people naturally move and relate them to gyroscope measurements of the actual motion. We used recordings of binaural signals in a number of rooms and listening scenarios (home, office, busy street etc). The listener's head movements were also recorded in synchrony with the audio, using a micro-electromechanical gyroscope. We calculated the instantaneous ILD and ITDs and analysed them over time and frequency, comparing them with measurements of head movements. The results showed that instantaneous ITDs were widely distributed across time and frequency in some multi-source environments while ILDs were less widely distributed. The type of listening environment affected head motion. These findings suggest a complex interaction between interaural cues, egocentric head movement and the identification of sound sources in real-world listening situations. PMID- 26879281 TI - Neurologic Outcomes in HIV-Exposed/Uninfected Infants Exposed to Antiretroviral Drugs During Pregnancy in Latin America and the Caribbean. AB - To evaluate antiretroviral (ARV) drug exposure and other factors during pregnancy that may increase the risk of neurologic conditions (NCs) in HIV exposed/uninfected (HEU) infants. A prospective cohort study was conducted at 24 clinical sites in Latin America and the Caribbean. Data on maternal demographics, health, HIV disease status, and ARV use during pregnancy were collected. Infant data included measurement of head circumference after birth and reported medical diagnoses at birth, 6-12 weeks, and 6 months. Only infants with maternal exposure to combination ARV therapy (cART) (>=3 drugs from >=2 drug classes) during pregnancy were included. Microcephaly, defined as head circumference for age z score less than -2, and NC were evaluated for their association with covariates, including individual ARVs, using bivariable and logistic regression analyses. From 2002 to 2009, 1,400 HEU infants met study inclusion criteria. At least one NC was reported in 134 (9.6%; 95% confidence interval [CI]: 8.1-11.2), microcephaly in 105 (7.5%; 95% CI: 6.2-9.0), and specific neurologic diagnoses in 33 (2.4%; 95% CI: 1.6-3.3) HEU infants. Microcephaly and NC were not significantly associated with any specific ARV analyzed (p > 0.05). Covariates associated with increased odds of NC included male sex (odds ratio [OR] = 1.9; 95% CI: 1.3-2.8), birth weight <2.5 kg (OR = 3.1; 95% CI: 2.1-4.8), 1-min Apgar score <7 (OR = 2.5; 95% CI: 1.4-4.4), and infant infections (OR = 2.5; 95% CI: 1.5-4.1). No ARV investigated was associated with adverse neurologic outcomes. Continued investigation of such associations may be warranted as new ARVs are used during pregnancy and cART exposure during the first trimester becomes increasingly common. PMID- 26879282 TI - Anaplastic thyroid carcinoma: Failure of conventional therapy but hope of targeted therapy. AB - BACKGROUND: Anaplastic thyroid cancer has a median survival between 1.2 and 10 months. The purpose of our study was to evaluate the outcomes of patients with anaplastic thyroid cancer in Ireland. METHODS: We carried out a retrospective analysis of the Irish National Cancer Database for patients with anaplastic thyroid cancer between 2000 and 2010. RESULTS: Of a total of 64 patients (40 women, 24 men), the median age was 69 years, and 29.7% of the patients had distant metastases. The overall median survival was 2.3 months and the 1, 2, and 5-year survival was 12.5%, 6.25%, and 4.69%, respectively. On univariate analysis age, sex, metastases at diagnosis, and multimodality treatment were statistically significant indicators of prognosis, and metastases at diagnosis remained statistically significant on multivariate analysis. CONCLUSION: These results correlate with the American Thyroid Association (ATA) guidelines, in which, when possible, multimodality therapy offers a survival advantage to a select group of patients. Novel therapies may offer the greatest hope for these patients. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1122-E1129, 2016. PMID- 26879283 TI - Surgical treatment of popliteal cyst: a systematic review and meta-analysis. AB - BACKGROUND: This systematic review and meta-analysis of the clinical efficacy of different surgical methods in the therapy of popliteal cysts may provide evidence about effective surgical treatments. METHODS: PubMed, EMBASE, and OVID were searched with the following terms: (popliteal cyst* OR baker's cyst*) AND (arthroscopic OR excision OR operative OR treat* OR surgery). Inclusion criteria included the following: studies reported the efficacy of different surgical methods in popliteal cyst patients; patients were >= 16 years; and studies must have involved a minimum of 10 patients. Studies were grouped according to the surgical methods, and a meta-analysis was employed to identify the success rate based on the pooled data. RESULTS: A total of 11 studies were included: The communication between the cyst and the articular cavity was enlarged in 7 studies; this communication was closed in 3 studies; and only intra-articular lesions were managed in 1 study. After the data were pooled, the success rates were 96.7 and 84.6 % in the communication-enlargement group and communication closure group, respectively. Studies with communication enlargement were subgrouped into the cyst wall resection group and the non-cyst wall resection group, for which the success rates were 98.2 and 94.7 %, respectively. CONCLUSIONS: Based on the current available evidence, at present, any how arthroscopic excision of the cyst wall, arthroscopic management of intra articular lesions, and enlarging the communication between the cyst and the articular cavity is an ideal strategy for the popliteal cyst. The current literature on the treatment of popliteal cysts is limited to retrospective case series. Future prospective studies with high-quality methodology and uniform scoring system are required to directly compare communication-enlargement surgery and communication-closure surgery and determine the optimal treatment of popliteal cysts. Cyst wall resection may improve the therapeutic efficacy, to draw definitive conclusions, and high-level clinical researches with a large number of patients and long-term follow-up should be initiated. PMID- 26879284 TI - Deciphering the biological effects of acupuncture treatment modulating multiple metabolism pathways. AB - Acupuncture is an alternative therapy that is widely used to treat various diseases. However, detailed biological interpretation of the acupuncture stimulations is limited. We here used metabolomics and proteomics technology, thereby identifying the serum small molecular metabolites into the effect and mechanism pathways of standardized acupuncture treatments at 'Zusanli' acupoint which was the most often used acupoint in previous reports. Comprehensive overview of serum metabolic profiles during acupuncture stimulation was investigated. Thirty-four differential metabolites were identified in serum metabolome and associated with ten metabolism pathways. Importantly, we have found that high impact glycerophospholipid metabolism, fatty acid metabolism, ether lipid metabolism were acutely perturbed by acupuncture stimulation. As such, these alterations may be useful to clarify the biological mechanism of acupuncture stimulation. A series of differentially expressed proteins were identified and such effects of acupuncture stimulation were found to play a role in transport, enzymatic activity, signaling pathway or receptor interaction. Pathway analysis further revealed that most of these proteins were found to play a pivotal role in the regulation of multiple metabolism pathways. It demonstrated that the metabolomics coupled with proteomics as a powerful approach for potential applications in understanding the biological effects of acupuncture stimulation. PMID- 26879285 TI - Verbal social primes alter motor contagion during action observation. AB - We investigated whether prosocial and nonsocial word primes prior to action observation modify subsequent initiation and execution of the observer's own reach-to-grasp actions. Participants observed a model performing exaggeratedly curved (vertical deviation) or natural straight reaches to a vertical dowel and always performed a straight reach to a dowel themselves. Observing curved movements slowed initiation times and increased the vertical deviation of the participants' movements. Observing curved movements enhanced vertical deviation only in the prosocial word primes condition. We suggest that social context priming can modulate initiation of movement as well as the extent of motor contagion (in this case, the extent of vertical deviation) between model and observer. PMID- 26879286 TI - Evaluation of a breast cancer nomogram to predict ipsilateral breast relapse after breast-conserving therapy. AB - BACKGROUND AND PURPOSE: A nomogram to predict for the 10-year ipsilateral breast relapse (IBR) after breast-conserving therapy (BCT) for breast cancer (BC) was developed based on the 'boost-no-boost'-trial with a concordance probability estimate (CPE) of 0.68. The aim of our study was to validate that algorithm. MATERIAL AND METHODS: We retrospectively identified 1787 BC cases, treated with BCT and radiotherapy at the University Hospitals Leuven from 2000 to 2007, without missing data of the nomogram variables. Clinicopathologic factors were assessed. Validity of the prediction model was tested in terms of discrimination and calibration. RESULTS: Median follow-up time was 10.75years. The validation cohort differed with respect to the administration of a radiation boost, chemo- or hormonal therapy, age, tumour diameter or grade, ductal carcinoma in situ and hormone receptor positivity. On multivariable analysis, the omission of the boost was a significant prognosticator of IBR (p<0.01). The 10-year IBR-rate was 1.4%. The nomogram demonstrated suboptimal discrimination (CPE 0.54) and calibration, with an overestimation of the IBR-risk in general. CONCLUSIONS: The predictive model for IBR in BC is imperfect in this more recent study population. PMID- 26879288 TI - Use of the Distance Transform for Integration of Local Measurements: Principle and Application in Chemical Engineering. AB - We propose an original methodology to integrate local measurement for nontrivial object shape. The method employs the distance transform of the object and least square fitting of numerically computed weighting functions extracted from it. The method is exemplified in the field of chemical engineering by calculating the global metal concentration in catalyst grains from uneven metal distribution profiles. Applying the methodology on synthetic profiles with the help of a very simple deposition model allows us to evaluate the accuracy of the method. For high symmetry objects such as an infinite cylinder, relative errors on global concentration are lower than 1% for well-resolved profiles. For a less symmetrical object, a tetralobe, the best estimator gives a relative error below 5% at the cost of increased measurement time. Applicability on a real case is demonstrated on an aged hydrodemetallation catalyst. Sampling of catalyst grains at the inlet and outlet of the reactor allowed conclusions concerning different reactivity for the trapped metals. PMID- 26879287 TI - Urinary bladder dose-response relationships for patient-reported genitourinary morbidity domains following prostate cancer radiotherapy. AB - BACKGROUND AND PURPOSE: Radiotherapy (RT) induced genitourinary (GU) morbidity is typically assessed by physicians as single symptoms or aggregated scores including symptoms from various domains. Here we apply a method to group patient reported GU symptoms after RT for localized prostate cancer based on their interplay, and study how these relate to urinary bladder dose. MATERIALS AND METHODS: Data were taken from two Scandinavian studies (N=207/276) including men treated with external-beam RT (EBRT) to 78/70Gy (2Gy/fraction; median time-to follow-up: 3.6-6.4y). Within and across cohorts, bladder dose-volume parameters were tested as predictors for GU symptom domains identified from two study specific questionnaires (35 questions on frequency, incontinence, obstruction, pain, urgency, and sensory symptoms) using univariate and multivariate logistic regression analysis (MVA) with 10-fold cross-validation. Performance was evaluated using Area Under the Receiver Operating Characteristic Curve (Az). RESULTS: For the identified Incontinence (2-5 symptoms), Obstruction (3-5 symptoms), and Urgency (2-7 symptoms) domains, MVA demonstrated that bladder doses close to the prescription doses were the strongest predictors for Obstruction (Az: 0.53-0.57) and Urgency (Az: 0.60). For Obstruction, performance increased for the across cohort analysis (Az: 0.61-0.64). CONCLUSIONS: Our identified patient-reported GU symptom domains suggest that high urinary bladder doses, and increased focus on both obstruction and urgency is likely to further add to the understanding of GU tract RT responses. PMID- 26879289 TI - Long-term molecular remission in Philadelphia-positive acute lymphoblastic leukemia elderly patient after dasatinib discontinuation. PMID- 26879290 TI - The use of azide-alkyne click chemistry in recent syntheses and applications of polytriazole-based nanostructured polymers. AB - The rapid development of efficient organic click coupling reactions has significantly facilitated the construction of synthetic polymers with sophisticated branched nanostructures. This Feature Article summarizes the recent progress in the application of efficient copper-catalyzed and copper-free azide alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star polymers, graft polymers, molecular brushes, and cyclic graft polymers. Literature reports on the interesting properties and functions of these polytriazole-based nanostructured polymers are also discussed to illustrate their potential applications as self-healing polymers, adhesives, polymer catalysts, opto-electronic polymer materials and polymer carriers for drug and imaging molecules. PMID- 26879291 TI - Effect of potential barrier height on the carrier transport in InGaAs/GaAsP multi quantum wells and photoelectric properties of laser diode. AB - The growth and strain-compensation behaviour of InGaAs/GaAsP multi-quantum wells, which were fabricated by metal-organic chemical vapor deposition, have been studied towards the application of these quantum wells in high-power laser diodes. The effect of the height of the potential barrier on the confined level of carrier transport was studied by incorporating different levels of phosphorus content into the GaAsP barrier. The crystal quality and interface roughness of the InGaAs/GaAsP multi-quantum wells with different phosphorus contents were evaluated by high resolution X-ray diffraction and in situ optical surface reflectivity measurements during the growth. The surface morphology and roughness were characterized by atomic force microscopy, which indicates the variation law of surface roughness, terrace width and uniformity with increasing phosphorus content, owing to strain accumulation. Moreover, the defect generation and structural disorder of the multi-quantum wells were investigated by Raman spectroscopy. The optical properties of the multi-quantum wells were characterized by photoluminescence, which shows that the spectral intensity increases as the phosphorus content increases. The results suggest that more electrons are well bound in InGaAs because of the high potential barrier. Finally, the mechanism of the effect of the height of the potential barrier on laser performance was proposed on the basis of simulation calculations and experimental results. PMID- 26879292 TI - Adsorption of silver nanoparticles from aqueous solution on copper-based metal organic frameworks (HKUST-1). AB - Silver nanoparticles (AgNP) are emerging pollutants. The use of novel materials such as Cu-(benzene 1,3,5-tricarboxylate, BTC) Metal-Organic Framework (MOFs), for AgNP adsorption and their removal from aqueous solutions has been studied. The effect of different parameters was followed and isotherm model was suggested. MOFs adsorbed fast and efficiently AgNP in the range C0 < 10 mg L(-1), being Freundlich isotherm (R = 0.993) these data fitted to. Among studied parameters a remarkable effect of chloride on sorption was found, thus their possible interactions were considered. The high adsorption efficiency of AgNP was achieved and it was found to be very fast. The feasibility of adsorption on Cu-(BTC) was proved in spiked waters. The results showed the potential interest of new material as adsorbent for removing AgNP from environment. PMID- 26879293 TI - Expression of Kir4.1 and Kir5.1 inwardly rectifying potassium channels in oligodendrocytes, the myelinating cells of the CNS. AB - The inwardly rectifying K+ channel subtype Kir5.1 is only functional as a heteromeric channel with Kir4.1. In the CNS, Kir4.1 is localised to astrocytes and is the molecular basis of their strongly negative membrane potential. Oligodendrocytes are the specialised myelinating glia of the CNS and their resting membrane potential provides the driving force for ion and water transport that is essential for myelination. However, little is known about the ion channel profile of mature myelinating oligodendrocytes. Here, we identify for the first time colocalization of Kir5.1 with Kir4.1 in oligodendrocytes in white matter. Immunolocalization with membrane-bound Na+/K+-ATPase and western blot of the plasma membrane fraction of the optic nerve, a typical CNS white matter tract containing axons and the oligodendrocytes that myelinate them, demonstrates that Kir4.1 and Kir5.1 are colocalized on oligodendrocyte cell membranes. Co immunoprecipitation provides evidence that oligodendrocytes and astrocytes express a combination of homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channels. Genetic knock-out and shRNA to ablate Kir4.1 indicates plasmalemmal expression of Kir5.1 in glia is largely dependent on Kir4.1 and the plasmalemmal anchoring protein PSD-95. The results demonstrate that, in addition to astrocytes, oligodendrocytes express both homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channels. In astrocytes, these channels are essential to their key functions of K+ uptake and CO2/H+ chemosensation. We propose Kir4.1/Kir5.1 channels have equivalent functions in oligodendrocytes, maintaining myelin integrity in the face of large ionic shifts associated with action potential propagation along myelinated axons. PMID- 26879295 TI - Commentary on: Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial. PMID- 26879294 TI - Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial. AB - BACKGROUND: In a previous study, the authors demonstrated that treatment with expanded adipose-derived stem cells or stromal vascular fraction (SVF)-enriched fat modify the pattern of the dermis in human beings, representing a skin rejuvenation effect. Considering that expanded stem cells require a cell factor, the authors wanted to assess similar results by replacing them with platelet-rich plasma (PRP), which is easier to obtain and for which an empirical regenerative effect has been already described. OBJECTIVES: To determine if PRP injection could replace the cutaneous regenerative effect of adipose-derived stem cells. METHODS: This study was performed in 13 patients who were candidates for facelift. The patients underwent sampling of fat by liposuction from the abdomen and submitted to one of three protocols: injection of SVF-enriched fat or expanded adipose-derived stem cells or fat plus PRP in the preauricular areas. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. RESULTS: The use of fat plus PRP led to the presence of more pronounced inflammatory infiltrates and a greater vascular reactivity, increasing in vascular permeability and a certain reactivity of the nervous component. The addition of PRP did not improve the regenerative effect. CONCLUSION: The use of PRP did not have significant advantages in skin rejuvenation over the use of expanded adipose-derived stem cells or SVF-enriched fat. The effect of increased vascular reactivity may be useful in pathological situations in which an intense angiogenesis is desirable, such as tissular ischemia. PMID- 26879296 TI - Preventing Elevated Radix Deformity in Asian Rhinoplasty with a Chimeric Dorsal Glabellar Construct. AB - BACKGROUND: Asian facial aesthetic surgery should enhance, but not change, natural features. Augmentation rhinoplasty is a hallmark of Asian cosmetic surgery. In the authors' experience, I-shaped implants can elevate and efface the radix, leading to an unnatural appearance (elevated radix deformity). OBJECTIVES: The Chimeric technique was developed to control final radix position and preserve the nasal profile. We aim to demonstrate that the Chimeric technique promotes forward projection, not elevation, of the radix. METHODS: Between 2013 and 2015, 49 patients underwent rhinoplasty with I-shaped implants. Nineteen patients had Chimeric dorsal-glabellar implants, 30 did not. Standardized photographs were obtained at every visit. Novel and established photogrammetric parameters were used to describe radix position and position change. A retrospective chart review provided additional procedural details and outcomes data. RESULTS: Patients were followed for 10.8 months (range, 2-36 months). Nasal height increase (113% vs 107%) and bridge length increase (118% vs 105%) were significantly greater when the Chimeric technique was not performed (P < .0001). The nasofrontal angle increased 6 degrees in both groups; there was no difference between groups. The vector of radix position change was 26.1 degrees in the Chimeric group and 63.4 degrees in the traditional group (P < .0001). CONCLUSIONS: The Chimeric technique preserves the nasal profile with a favorable (horizontal) radix transposition vector. There was not a significant difference in final radix position when Chimeric rhinoplasty was performed because that is controlled by implant thickness and position. The technique did not blunt the radix significantly. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26879297 TI - Commentary on: The Relationship of Bacterial Biofilms and Capsular Contracture in Breast Implants. PMID- 26879298 TI - Commentary on: Prevalence of Body Dysmorphic Disorder Symptoms and Body Weight Concerns in Patients Seeking Abdominoplasty. PMID- 26879299 TI - A Multicenter Study for Cellulite Treatment Using a 1440-nm Nd:YAG Wavelength Laser with Side-Firing Fiber. AB - BACKGROUND: Treatment of cellulite using a 1440-nm YAG wavelength laser with side firing fiber has proven safe and effective, lasting at least 6 months. OBJECTIVES: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite for at least 1 year. METHODS: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440 nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the blinded evaluators to distinguish baseline photos from those taken at 12 months posttreatment, with results on a 5-point, 2 category ordinal photonumeric scale when comparing baseline photos to 12 months posttreatment. Subject and physician satisfaction was assessed based on completion of a satisfaction survey. Adverse events (AE) were recorded throughout the study. Twelve month data were analyzed and compared to 6 month data. RESULTS: Evaluators chose baseline photographs 97% on average from 6 (-1, +2) months and 91% from the 12 (-3, +2) months posttreatment photographs. At 6 (-1, +2) months, the average improvement score was 1.7 for dimples and 1.1 for contour irregularities. At 12 (-3, +2) months, the average improvement score was 1.4 for dimples and 1.0 for contour irregularities. The average satisfaction score for the physician was 5.6 and the patient was 5.3 on a 6-point scale. CONCLUSIONS: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 1 year post treatment. LEVEL OF EVIDENCE 2: Therapeutic. PMID- 26879300 TI - Commentary on: Treatment of Prominent Ears with an Implantable Clip System: A Pilot Study. PMID- 26879301 TI - Suture With Resorbable Cones: Histology and Physico-Mechanical Features. AB - BACKGROUND: Silhouette Sutures (Kolster Methods, Inc., Corona, CA) exhibit different biological characteristics at various time points after their placement. OBJECTIVES: The goals of this study were to understand the biological reactions of Silhouette Sutures in human tissues at different time intervals and to determine the index of resistance of the sutures in subcutaneous tissue. METHODS: Histologic examination was performed on section soft tissue containing the sutures at 1 month, 3 months, 6 months, and 1 year after suture placement. The study comprised 8 patients, each of whom received 4 sutures in the lower abdomen under local anesthesia. The sutures were placed exactly 1 month, 3 months, 6 months, and 1 year before planned post-bariatric abdominal surgery. Dynamometric evaluation was performed on a never-used suture and on sutures removed from 1 year after placement. The scar process around the threads was also examined. RESULTS: A progressive increase in scar tissue around the sutures was observed. One year after placement, there was a reduction of 16.7% in yield and tensile strength and a reduction of 14.29% in elongation at break, relative to the never-used suture. By 1 year, the cones in polylactic and glycolic acids had been replaced by scar tissue. CONCLUSIONS: Fibrous tissue around the sutures increased progressively over time, and was most prominent at the level of the nodes. Cones were completely resorbed within 6 months. A reduction in the index of resistance of the suspension sutures occurred over 1 year. PMID- 26879302 TI - Facelift for an Ehlers-Danlos Syndrome Patient: A Case Report. PMID- 26879303 TI - Diabetes and Menopause. AB - During menopause, women's body composition, sex hormone profile, and metabolic profile may change dramatically. In this review, we summarize studies examining whether the menopausal transition and physiologic factors characterizing the transition are associated with increased risk of diabetes. We review the evidence for estrogen therapy and diabetes risk and studies examining the relationship between diabetes and menarche, which represents an extension of the reproductive life span at the opposite end of the age spectrum. Although studied less extensively, the presence of type 1 or type 2 diabetes may increase the risk of ovarian failure, and we review this literature. In conclusion, we note that the evidence linking menopausal sex hormone changes with increased diabetes risk is weak, although rapid changes as observed with oophorectomy may increase risk. Further studies should investigate the contradictory effects of estrogen therapy upon hepatic and glucose metabolism in mid-life women. PMID- 26879305 TI - Role of Medical Nutrition Therapy in the Management of Gestational Diabetes Mellitus. AB - Medical nutrition therapy (MNT) plays an important role in the management of gestational diabetes mellitus (GDM), and accordingly, it has a significant impact on women and newborns. The primary objective of MNT is to ensure adequate pregnancy weight gain and fetus growth while maintaining euglycemia and avoiding ketones. However, the optimal diet (energy content, macronutrient distribution, its quality and amount, among others) remains an outstanding question. Overall, the nutritional requirements of GDM are similar for all pregnancies, but special attention is paid to carbohydrates. Despite the classical intervention of restricting carbohydrates, the latest evidence, although limited, seems to favor a low-glycemic index diet. There is general agreement in the literature about caloric restrictions in the case of being overweight or obese. Randomized controlled trials are necessary to investigate the optimal MNT for GDM; this knowledge could yield health benefits and cost savings. PMID- 26879304 TI - Bariatric Surgery and the Pregnancy Complicated by Gestational Diabetes. AB - Gestational diabetes mellitus (GDM) is an increasingly common obstetrical problem. Due to the global escalation in the prevalence of obesity, as many as 15 % of pregnant women may soon be classified as having GDM. While often not diagnosed until late gestation, GDM is now recognized as a disorder of glucose and lipid metabolism, systemic inflammation, and insulin resistance that begins early in pregnancy. Recent large randomized trials have clarified the risk of maternal and neonatal complications caused by GDM, as well as the potential to ameliorate these risks. There is significant interest in the potential to reduce the risk for developing GDM in obese women through the performance of bariatric surgery (BS) before pregnancy. BS significantly reduces the risk for GDM, preeclampsia, and large neonates. However, it seems that the risk for small neonates and preterm delivery is increased. No significant differences are observed in regard to cesarean section, postpartum hemorrhage, or perinatal mortality. In this article, we address the effects of GDM on the mother and child, and explore the risks and benefits of BS in the obstetrical population. PMID- 26879306 TI - Perioperative Glycemic Management of Patients Undergoing Bariatric Surgery. AB - Bariatric surgery in patients with type 2 diabetes has been shown to improve glycemic control and reduce need for glucose-lowering medications. Some of these improvements occur in the early postoperative period prior to any weight loss. These early reductions in circulating glucose can be attributed to primarily perioperative caloric restriction and prolonged fasting. Inpatient glycemic targets for patients undergoing bariatric surgery are similar to those recommended for other surgical procedures as a way of minimizing risk for complications. There is evidence that achieving perioperative and postoperative glycemic targets can improve the ability to achieve remission of type 2 diabetes following gastric bypass surgery. This review provides recommendations regarding glycemic goals, strategies for achieving these goals with minimal risk for hypoglycemia, and an examination of the data suggesting an association between perioperative glycemic management and diabetes remission following bariatric surgery. PMID- 26879307 TI - Has RAAS Blockade Reached Its Limits in the Treatment of Diabetic Nephropathy? AB - Medications that block the renin-angiotensin-aldosterone system (RAAS) are a cornerstone of diabetic nephropathy treatment. These agents play an important role in slowing the nephropathy progression in patients with diabetes. Clinical outcome trials that investigated use of these drug classes in patients with diabetic nephropathy have demonstrated clinical significant benefit in slowing nephropathy progression only in people with >300 mg/day of proteinuria. Thus, guidelines mandate their use in such patients. Conversely, combinations of RAAS blocking agents in these patients can worsen renal outcomes. Moreover, use of RAAS blockers in patients with a glomerular filtration rate below 45 mL/min/1.73 m(2) is limited by hyperkalemia. New agents that predictably bind excess potassium in the colon offer the possibility of extending RAAS inhibitor use in advanced chronic kidney disease (CKD) to allow evaluation of RAAS blockade for nephropathy and cardiovascular outcomes. These new potassium-binding agents may provide an opportunity to continue full-dose RAAS inhibition and assess if the benefits of RAAS blockade seen in stage 3 CKD can be extrapolated to persons with stages 4 and 5 CKD, not previously tested due to hyperkalemia. PMID- 26879308 TI - Intensive Glycemic Control in Cardiac Surgery. AB - Hyperglycemia has been found to be associated with increased morbidity and mortality in surgical patients, yet, the optimal glucose management strategy during the perioperative setting remains undetermined. While much has been published about hyperglycemia and cardiac surgery, most studies have used widely varying definitions of hyperglycemia, methods of insulin administration, and the timing of therapy. This has only allowed investigators to make general conclusions in this challenging clinical scenario. This review will introduce the basic pathophysiology of hyperglycemia in the cardiac surgery setting, describe the main clinical consequences of operative hyperglycemia, and take the reader through the published material of intensive and conservative glucose management. Overall, it seems that intensive control has modest benefits with adverse effects often outweighing these advantages. However, some studies have indicated differing results for certain patient subgroups, such as non-diabetics with acute operative hyperglycemia. Future studies should focus on distinguishing which patient populations, if any, would optimally benefit from intensive insulin therapy. PMID- 26879310 TI - High perfluorooctanoic acid exposure induces autophagy blockage and disturbs intracellular vesicle fusion in the liver. AB - Perfluorooctanoic acid (PFOA) has been shown to cause hepatotoxicity and other toxicological effects. Though PPARalpha activation by PFOA in the liver has been well accepted as an important mechanism of PFOA-induced hepatotoxicity, several pieces of evidence have shown that the hepatotoxic effects of PFOA may not be fully explained by PPARalpha activation. In this study, we observed autophagosome accumulation in mouse livers as well as HepG2 cells after PFOA exposure. Further in vitro study revealed that the accumulation of autophagosomes was not caused by autophagic flux stimulation. In addition, we observed that PFOA exposure affected the proteolytic activity of HepG2 cells while significant dysfunction of lysosomes was not detected. Quantitative proteomic analysis of crude lysosomal fractions from HepG2 cells treated with PFOA revealed that 54 differentially expressed proteins were related to autophagy or vesicular trafficking and fusion. The proteomic results were further validated in the cells in vitro and livers in vivo after PFOA exposure, which implied potential dysfunction at the late stage of autophagy. However, in HepG2 cells, it seemed that further inhibition of autophagy did not significantly alter the effects of PFOA on cell viability. Although these findings demonstrate that PFOA blocked autophagy and disturbed intracellular vesicle fusion in the liver, the changes in autophagy were observed only at high cytotoxic concentrations of PFOA, suggesting that autophagy may not be a primary target or mode of toxicity. Furthermore, since altered liver autophagy was not observed at concentrations of PFOA associated with human exposures, the relevance of these findings must be questioned. PMID- 26879309 TI - Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus. AB - With increasing rates of obesity and new diagnostic criteria for gestational diabetes mellitus (GDM), the overall prevalence of GDM is increasing worldwide. Women with GDM have an increased risk of maternal and fetal complications during pregnancy as well as long-term risks including higher prevalence of type 2 diabetes mellitus and cardiovascular disease. In recent years, the role of immune activation and inflammation in the pathogenesis of GDM has gained increasing attention. This monograph explores the current state of the literature as regards the expression of markers of inflammation in the maternal circulation, placenta, and adipose tissue of women with GDM. PMID- 26879311 TI - Fatigue, sleep-wake pattern, depressive and anxiety symptoms and body-mass index: analysis in a sample of episodic and chronic migraine patients. AB - Migraine clinical presentation and life-time course can be highly heterogeneous, with a subgroup of patients developing chronic migraine; moreover, migraine clinical spectrum is expanded by the association with different coexisting conditions and interictal dysfunctions. The aim of this study was to systematically evaluate migraine clinical features, daily functioning parameters, sleep pattern, presence of depressive-anxiety symptoms and body mass index (BMI) in a sample of 75 episodic and 75 chronic migraine without aura patients. Migraine-related disability, fatigue, daily sleepiness, subjective sleep quality, anxiety and depressive symptoms were, respectively, evaluated using the following questionnaires: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire 9-item Scale (PHQ-9). Mean FSS score (p < 0.001), PSQI score (p = 0.015), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.012) were significantly higher in chronic compared to episodic migraineurs. Additionally, a correlation analysis carried out in the total sample of 150 migraine patients documented a statistically significant, positive correlation between monthly frequency of migraine attacks and FSS score (p < 0.001), PSQI score (p = 0.006), GAD-7 score (p = 0.019), PHQ-9 score (p < 0.001) and BMI score (p = 0.049). Data from the present report seem to expand the concept of migraine as a continuum or spectrum, with greater occurrence of fatigue, poor sleep quality, anxiety-depressive symptoms and higher BMI score in chronic compared to episodic migraine patients; further investigation is certainly necessary to better define the biological basis and mechanisms associated with migraine transformation from episodic to chronic pattern. PMID- 26879313 TI - Postural orthostatic tachycardia syndrome (POTS) as presenting symptom of CIDP. PMID- 26879312 TI - Indoor and outdoor falls in persons with Parkinson's disease after 1 year follow up study: differences and consequences. AB - Falls among persons with Parkinson's disease (PD) often result in activity limitations, participation restrictions, social isolation or premature mortality. The purpose of this 1-year follow-up study was to compare potential differences in features of PD attributing to falls in relation to fall location (outdoor vs. indoor). We recruited 120 consecutive persons with PD who denied having fallen in the past 6 months. Disease stage and severity was assessed using the Hoehn and Yahr scale and the newer version of the Unified Parkinson's Disease Rating Scale. Occurrence of falling and characteristics of falls was followed for 1 year. Results were assessed statistically. Outdoor falls were more commonly preceded by the extrinsic factors (tripping and slipping). Slipping was more common outdoors (p = 0.001). Indoor falls were mostly preceded by the intrinsic factors (postural instability, lower extremity weakness, vertigo). Vertigo was more common indoors (p = 0.006). Occurrence of injuries was more common after outdoor falls (p = 0.001). Indoor falls resulted in contusions only, while outdoor falls resulted in lacerations and fractures as well. In the regression model adjusted for age, disease duration, on/off phase during fall, Hoehn and Yahr stage of disease and levodopa dosage, slipping was associated with outdoor falling (odds ratio = 17.25, 95 % confidence interval 3.33-89.20, p = 0.001). These findings could be used to tailor fall prevention program with emphasis on balance recovery and negotiation of objects in environment. PMID- 26879314 TI - Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors. AB - A series of novel morpholin-3-one-fused quinazoline derivatives were designed, synthesized and evaluated as EGFR tyrosine kinase inhibitors. Nineteen compounds showed significant inhibitory activities against EGFR(wt) kinase (IC50<1 MUM). Compound a8 demonstrated the most potent inhibitory activity toward EGFR(wt) (IC50=53.1 nM). Compound a7 and a8 showed excellent inhibitory activities against mutant EGFR(T790M/L858R) and strong antiproliferative activity against H358 and A549 cell lines. Finally, molecular docking studies were performed to predict the possible binding mode of the target compounds. It is believed that this work would be very useful for designing a new series of tyrosine kinase inhibitors targeting EGFR. PMID- 26879315 TI - Relationship of toe pinch force to other muscle strength parameters in men with type 2 diabetes. AB - OBJECTIVE: The aim of this study was to explore the relations between toe pinch force and other muscle strength parameters in male patients with type 2 diabetes mellitus. METHODS: A total of 40 men with type 2 diabetes (age: 53.4 +/- 13.1 years, duration of diabetes: 8.5 +/- 8.1 years) who needed exercise training were enrolled in this cross-sectional study. We evaluated the clinical parameters and 4 muscle strength parameters, which were toe pinch force, handgrip strength, isometric knee extension force, and isometric ankle dorsiflexion force. RESULTS: The HbA1c, toe pinch force, handgrip strength, isometric knee extension force, and isometric ankle dorsiflexion force were 10.1 +/- 2.4 %, 3.2 +/- 1.2 kg, 37.3 +/- 7.0 kg, 39.6 +/- 11.4 kgf, and 17.0 +/- 6.3 kgf, respectively. Toe pinch force was significantly correlated with handgrip strength (r = 0.365, p = 0.0206), isometric knee extension force (r = 0.668, p < 0.0001), and isometric ankle dorsiflexion force (r = 0.514, p = 0.0007). All muscle strength parameters were significantly lower in patients with diabetic polyneuropathy than in those without polyneuropathy. CONCLUSION: Although toe pinch force was significantly correlated with the other muscle strength parameters, the correlation was not so strong. However, evaluation of toe pinch force might be recommended for assessment of distal limb muscle strength in patients with type 2 diabetes. PMID- 26879316 TI - Targeted disruption of EBNA1 in EBV-infected cells attenuated cell growth. AB - Epstein Barr virus (EBV)-encoded nuclear antigen-1 (EBNA1) plays a pivotal in an EBV episome replication and persistence. Despite considerable attempts, there are no EBV drugs or vaccines. We attempted to eradicate EBV episomes by targeting EBNA1 using the transcription activator-like effector nucleases (TALEN) (E1TN). E1TN-mediated transient knockout (KO) of EBNA1 reduced EBNA1 expression, and caused significant loss of EBV genomes and progressive death of EBV-infected cells. Furthermore, when a mixture of EBV-infected Burkitt's lymphoma (BL) cells and EBV-negative BL cells was targeted by E1TN, EBV-negative cells were counter selected while most EBV-infected cells died, further substantiating that EBNA1 KO caused selective death of EBV-infected cells. TALEN-mediated transient targeting of EBNA1 attenuated the growth of EBV-infected cells, implicating a possible therapeutic application of E1TN for EBV-associated disorders. [BMB Reports 2016; 49(4): 226-231]. PMID- 26879317 TI - Anti-inflammatory action of ethanolic extract of Ramulus mori on the BLT2-linked cascade. AB - Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL 6 production by blocking the leukotriene B4 receptor- 2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase- cytosolic phospholipase A2-5 /12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti inflammatory action of R. mori. [BMB Reports 2016; 49(4): 232-237]. PMID- 26879318 TI - Biphasic activation of extracellular signal-regulated kinase (ERK) 1/2 in epidermal growth factor (EGF)-stimulated SW480 colorectal cancer cells. AB - Cancer cells have different characteristics due to the genetic differences where these unique features may strongly influence the effectiveness of therapeutic interventions. Here, we show that the spontaneous reactivation of extracellular signalregulated kinase (ERK), distinct from conventional ERK activation, represents a potent mechanism for cancer cell survival. We studied ERK1/2 activation in vitro in SW480 colorectal cancer cells. Although ERK signaling tends to be transiently activated, we observed the delayed reactivation of ERK1/2 in epidermal growth factor (EGF)-stimulated SW480 cells. This effect was observed even after EGF withdrawal. While phosphorylated ERK1/2 translocated into the nucleus following its primary activation, it remained in the cytoplasm during late-phase activation. The inhibition of primary ERK1/2 activation or protein trafficking, blocked reactivation and concurrently increased caspase 3 activity. Our results suggest that the biphasic activation of ERK1/2 plays a role in cancer cell survival; thus, regulation of ERK1/2 activation may improve the efficacy of cancer therapies that target ERK signaling. [BMB Reports 2016; 49(4): 220-225]. PMID- 26879319 TI - Adapting a Cancer Literacy Measure for Use Among Navajo Women. AB - PURPOSE: The authors designed a community-based participatory research study to develop and test a family-based behavioral intervention to improve cancer literacy and promote mammography among Navajo women. METHOD: Using data from focus groups and discussions with a community advisory committee, they adapted an existing questionnaire to assess cancer knowledge, barriers to mammography, and cancer beliefs for use among Navajo women. Questions measuring health literacy, numeracy, self-efficacy, cancer communication, and family support were also adapted. RESULTS: The resulting questionnaire was found to have good content validity, and to be culturally and linguistically appropriate for use among Navajo women. CONCLUSIONS: It is important to consider culture and not just language when adapting existing measures for use with AI/AN (American Indian/Alaskan Native) populations. English-language versions of existing literacy measures may not be culturally appropriate for AI/AN populations, which could lead to a lack of semantic, technical, idiomatic, and conceptual equivalence, resulting in misinterpretation of study outcomes. PMID- 26879320 TI - Anti-DNase I antibodies in systemic lupus erythematosus: diagnostic value and share in the enzyme inhibition. AB - Diagnostic accuracy of anti-DNase I antibodies measurement in a differentiation between SLE and other autoimmune rheumatic diseases was evaluated. The share of anti-DNase I and actin in the DNase I activity decrease in SLE was established. Serum samples were obtained from 54 patients with verified SLE, 52 control patients with other autoimmune rheumatic diseases, and 44 healthy persons. Anti DNase I concentrations were measured by ELISA. Free and actin inhibited DNase I activities were evaluated in the fresh serum samples. The appraisal of antibodies and actin effects on DNase I activity was made using multiple regression. Anti DNase I antibodies were positive in 35 SLE and 8 control patients, without significant difference between the mean antibody concentrations. Sensitivity of this test was 64.81 %, and specificity-84.62 %. Mean free DNase I activity in SLE was somewhat lower than in the control group as a result of augmented frequency of extremely low enzyme activities. On the contrary, after the exclusion of the latter cases we have revealed elevated mean free DNase I activity in the other SLE patients comparing to the similar control subgroup. Unlike the controls, low serum DNase I activity in SLE arose not only from actin and antibody action, but also, in half of the cases, from unidentified factor, related to active SLE. The accuracy of the anti-DNase I antibodies measurement is approximate to the present reference standard of SLE diagnostics. We first demonstrated that neither antibodies nor actin caused DNase I activity decrease in SLE. PMID- 26879321 TI - Psychological factors associated with failure of detoxification treatment in chronic headache associated with medication overuse. AB - AIM: The aim of this study was to evaluate the psychological factors associated with a negative outcome following detoxification in a 2-month follow-up in medication-overuse headache. METHODS: All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion. Psychiatric conditions and personality characteristics were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I) and the Minnesota Multiphasic Personality Inventory (MMPI)-2. chi2 tests, one-way analyses of variance, and odds ratios (ORs) were used. RESULTS: A total of 248 patients completed the follow-up: 156 stopped overuse and their headaches reverted to an episodic pattern (Group A); 23 kept overusing without any benefit on headache frequency (Group B); and 51 stopped overuse without any benefit on headache frequency (Group C). The prognostic factors for the outcome of Group B were higher scores on the correction (OR 1.128; p = 0.036), depression (OR 1.071; p = 0.05), hysteria (OR 1.106; p = 0.023), and overcontrolled hostility (OR 1.182; p = 0.04) MMPI-2 scales, whereas those for Group C were psychiatric comorbidities (OR 1.502; p = 0.021) and higher scores on the hysteria scale (OR 1.125; p = 0.004). CONCLUSIONS: The outcome of detoxification is influenced by psychological factors that should be considered when considering treatment strategies. PMID- 26879324 TI - Erratum to: Enzalutamide: A Step Towards Pharmacokinetic-Based Dosing in Men with Metastatic Castration-Resistant Prostate Cancer. PMID- 26879322 TI - Chordoid glioma of the third ventricle: a patient presenting with SIADH and a review of this rare tumor. AB - INTRODUCTION: Chordoid glioma of the third ventricle is a rare and recently described tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Its clinical, radiological and histological features may vary. Despite the fact that chordoid glioma is a low-grade tumor, its prognosis has been relatively poor because of its insidious presentation and the difficulty in obtaining complete surgical resection. MATERIALS AND METHODS: Here, we report on a new case of chordoid glioma occurring in a 48-year-old woman, presented with hyponatremia, and on the initial work-up with a diagnosis of hyponatremia due at least in part to SIADH. We review the current literature on this rare pathology, discuss the radiological and histopathologic findings, and discuss the optimal management of chordoid glioma in general. CONCLUSION: Based on this new case and the previous literature reports, we suggest that chordoid glioma should be included in the differential diagnosis of uncommon masses of the third ventricle, especially in middle-aged women, and we emphasize current management guidelines. PMID- 26879323 TI - Incorporating specificity into optimization: evaluation of SPA using CSAR 2014 and CASF 2013 benchmarks. AB - Scoring functions of protein-ligand interactions are widely used in computationally docking software and structure-based drug discovery. Accurate prediction of the binding energy between the protein and the ligand is the main task of the scoring function. The accuracy of a scoring function is normally evaluated by testing it on the benchmarks of protein-ligand complexes. In this work, we report the evaluation analysis of an improved version of scoring function SPecificity and Affinity (SPA). By testing on two independent benchmarks Community Structure-Activity Resource (CSAR) 2014 and Comparative Assessment of Scoring Functions (CASF) 2013, the assessment shows that SPA is relatively more accurate than other compared scoring functions in predicting the interactions between the protein and the ligand. We conclude that the inclusion of the specificity in the optimization can effectively suppress the competitive state on the funnel-like binding energy landscape, and make SPA more accurate in identifying the "native" conformation and scoring the binding decoys. The evaluation of SPA highlights the importance of binding specificity in improving the accuracy of the scoring functions. PMID- 26879325 TI - Photochemical Hydrogen Generation Initiated by Oxidative Quenching of the Excited Ru(bpy)3 (2+) * by a Bio-Inspired [2Fe2S] Complex. AB - A diiron dithiolate complex 1 containing 1,8-naphthalic anhydride bridge was prepared, which possessed the lowest reduction potential for the synthetic diiron complexes modeled on the active site of [FeFe] hydrogenase reported so far. For the first time, oxidative quenching of the excited Ru(bpy)3 (2+) * through electron transfer to a bio-inspired [2Fe2S] complex was corroborated. Hydrogen evolution, driven by visible light, was successfully observed for a three component system, consisting of Ru(bpy)3 (2+) , complex 1, and EDTA as electron donor in aqueous/organic media. These results provide a basis and also opportunity to develop a photo water splitting system employing Fe-based catalysts without sacrificial electron donors. PMID- 26879326 TI - Determining prevalence of maltreatment among children in the kingdom of Saudi Arabia. AB - PURPOSE: The aim of this study is to find out the overall prevalence rates for the major forms of abuse among adolescents in the Kingdom of Saudi Arabia and the differences in prevalence by age, gender and living arrangement. METHODS: The cross-sectional study was conducted in secondary high schools in five of the 13 main regions of Kingdom of Saudi Arabia during 2012. Through a multistage stratified sampling technique, a sample (n = 16 939) of adolescents (15-19 years) were identified and invited to participate. The ISPCAN Child Abuse Screening Tool - Child was used for data collection. The previous year's occurrence of violence exposure, psychological, physical and sexual abuse, and neglect were assessed. RESULTS: Nearly 90% of the adolescents were between 16 and 18 years of age, and over 80% were cared for by both of their biological parents. Annual prevalence of various forms of abuse in the year before the 2012 assessment ranged between 0.10 and 0.65, with the lowest rate for sexual abuse and the highest for psychological abuse. Significantly, greater rates of all forms of abuse/exposure were found when participants lived with their mother or father only (versus with both), and even greater rates for all when they lived with their biological parent and a step-parent. Rates for violence exposure, psychological abuse and neglect were significantly greater for girls, and rate of sexual abuse was greater for boys. CONCLUSIONS: More attention should be given to the effect of adolescent maltreatment particularly among girls. In addition, sexual abuse prevention programme should be targeted among boys. PMID- 26879327 TI - The effects of a rotator cuff tear on activities of daily living in older adults: A kinematic analysis. AB - Rotator cuff tears (RCT) in older individuals may compound age-associated physiological changes and impact their ability to perform daily functional tasks. Our objective was to quantify thoracohumeral kinematics for functional tasks in 18 older adults (mean age=63.3+/-2.2), and compare findings from nine with a RCT to nine matched controls. Motion capture was used to record kinematics for 7 tasks (axilla wash, forward reach, functional pull, hair comb, perineal care, upward reach to 90 degrees , upward reach to 105 degrees ) spanning the upper limb workspace. Maximum and minimum joint angles and motion excursion for the three thoracohumeral degrees of freedom (elevation plane, elevation, axial rotation) were identified for each task and compared between groups. The RCT group used greater minimum elevation angles for axilla wash and functional pull (p<=0.0124) and a smaller motion excursion for functional pull (p=0.0032) compared to the control group. The RCT group also used a more internally rotated maximum axial rotation angle than controls for functional reach, functional pull, hair comb, and upward reach to 105 degrees (p<=0.0494). The most differences between groups were observed for axial rotation, with the RCT group using greater internal rotation to complete functional tasks, and significant differences between groups were identified for all three thoracohumeral degrees of freedom for functional pull. We conclude that older adults with RCT used more internal rotation to perform functional tasks than controls. The kinematic differences identified in this study may have consequences for progression of shoulder damage and further functional impairment in older adults with RCT. PMID- 26879328 TI - Azilsartan, an angiotensin II type 1 receptor blocker, attenuates tert-butyl hydroperoxide-induced endothelial cell injury through inhibition of mitochondrial dysfunction and anti-inflammatory activity. AB - Angiotensin II type 1 receptor (AT1-R) blockers protect against brain ischemia by mechanisms dependent on and independent of arterial blood pressure. However, the effects of AT1-R blockers on brain endothelial cell injury and detailed mechanisms remain unclear. The goal of this study is to investigate whether azilsartan, an AT1-R blocker, could attenuate oxidative injury in endothelial cells via regulating mitochondrial function and inflammatory responses. We found that treatment with azilsartan suppressed tert-butyl hydroperoxide (t-BHP) induced oxidative damage in murine brain endothelial cells (mBECs) by increasing cell viability, decreasing lactate dehydrogenase (LDH) release and inhibiting cell apoptosis. Azilsartan significantly inhibited reactive oxygen species (ROS) generation and lipid peroxidation, but had no effect on antioxidant system. We also detected preserved mitochondrial function after azilsartan treatment, as evidenced by increased mitochondrial membrane potential (MMP), reduced cytochrome c release, preserved ATP synthesis and inhibited mitochondrial swelling. In addition, azilsartan differently regulated expression of inflammatory cytokines and increased the activation of endothelial nitric oxide synthase (eNOS). Pretreatment with eNOS inhibitor L-NIO partially prevented the azilsartan-induced regulation of cytokines and protection. Furthermore, azilsartan-induced protection in our in vitro model was shown to be associated with protein stability of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Overall, our data suggest that the AT1-R blocker azilsartan may have therapeutic values in treating endothelial dysfunction associated neurological disorders through anti-oxidative and anti-inflammatory properties. PMID- 26879329 TI - Development of a web-based epidemiological surveillance system with health system response for improving maternal and newborn health: Field-testing in Thailand. AB - Surveillance systems are yet to be integrated with health information systems for improving the health of pregnant mothers and their newborns, particularly in developing countries. This study aimed to develop a web-based epidemiological surveillance system for maternal and newborn health with integration of action oriented responses and automatic data analysis with results presentations and to assess the system acceptance by nurses and doctors involved in various hospitals in southern Thailand. Freeware software and scripting languages were used. The system can be run on different platforms, and it is accessible via various electronic devices. Automatic data analysis with results presentations in the forms of graphs, tables and maps was part of the system. A multi-level security system was incorporated into the program. Most doctors and nurses involved in the study felt the system was easy to use and useful. This system can be integrated into country routine reporting system for monitoring maternal and newborn health and survival. PMID- 26879330 TI - Laboratory diagnosis of gestational diabetes mellitus. PMID- 26879331 TI - Divergent genes in potential inoculant Sinorhizobium strains are related to DNA replication, recombination, and repair. AB - To serve as inoculants of legumes, nitrogen-fixing rhizobium strains should be competitive and tolerant of diverse environments. We hybridized the genomes of symbiotically efficient and salt tolerant Sinorhizobium inoculant strains onto the Sinorhizobium meliloti Rm1021 microarray. The number of variable genes, that is, divergent or putatively multiplied genes, ranged from 503 to 1556 for S. meliloti AK23, S. meliloti STM 1064 and S. arboris HAMBI 1552. The numbers of divergent genes affiliated with the symbiosis plasmid pSymA and related to DNA replication, recombination and repair were significantly higher than expected. The variation was mainly in the accessory genome, implying that it was important in shaping the adaptability of the strains. PMID- 26879332 TI - Detection of aristolochic acids I and II in "Chiniy-tref", a traditional medicinal preparation containing caterpillars feeding on Aristolochia trilobata L. in Martinique, French West Indies. AB - "Chiniy-tref" is a traditional medicinal preparation used in Martinique, French West Indies, for the prevention of all kinds of attempted poisoning and hex. It is produced by the maceration in alcohol (mostly rum) of larvae (caterpillars) of the butterfly Battus polydamas ssp. cebriones, feeding on the leaves of Aristolochia trilobata. Aristolochic acids I and II that are well-known nephrotoxic and carcinogenic substances were identified on two samples of "chiniy trefl" by chromatographic methods. PMID- 26879333 TI - Response to the letter by Nicholas G. Kounis, George D. Soufras. PMID- 26879334 TI - Complications and revision of reverse total shoulder arthroplasty. AB - The most common causes of revision surgery after reverse total shoulder arthroplasty (RTSA) are, in decreasing order: prosthetic instability (38%), infection (22%), humeral problems (21%) including loosening, unscrewing and fracture, and, lastly, problems of glenoid loosening (13%). Complications leading to reoperation are often multiple and their association is underestimated. It is not uncommon for patients to be reoperated several times due to the persistence of the same complication, failure to diagnose associated complications, or onset of an additional complication. Although it may require a number of procedures in the same patient, it is very often possible (in 90% of cases, in our experience) to conserve or replace the RTSA, allowing patients to recover a functional shoulder. However, the functional results of revised RTSA are inferior than for primary prostheses, and depend on the surgeon's experience and the number of RTSAs performed, suggesting that patients should be referred to a tertiary center. PMID- 26879335 TI - Safety analysis of long-term budesonide nasal irrigations in patients with chronic rhinosinusitis post endoscopic sinus surgery. AB - BACKGROUND: Although the safety of topical nasal steroids is well established for nasal spray forms, data regarding the safety of steroid irrigations is limited. We studied the effect of long-term budesonide nasal irrigations (>6 months) on hypothalamic-pituitary-adrenal axis (HPAA) function and intraocular pressure (IOP) in patients post-endoscopic sinus surgery. METHODS: This was retrospective case series. Adrenal function was assessed by using the high-dose cosyntropin stimulation test. RESULTS: A total of 48 patients were assessed, with a mean duration of budesonide irrigations of 22 months. Stimulated cortisol levels were abnormally low in 11 patients (23%). None reported to have symptoms of adrenal suppression. Three of 4 patients who repeated the study being off budesonide for at least 1 month returned to near normal levels. Logistic regression analysis revealed that concomitant use of both nasal steroid sprays and pulmonary steroid inhalers was significantly associated with HPAA suppression (p = 0.024). Patients with low stimulated cortisol levels were able to continue budesonide irrigations under the supervision of an endocrinologist without frank clinical manifestations of adrenal insufficiency. IOP was within normal limits in all patients. CONCLUSION: Long-term use of budesonide nasal irrigations is generally safe, but asymptomatic HPAA suppression may occur in selected patients. Concomitant use of both nasal steroid sprays and pulmonary steroid inhalers while using daily budesonide nasal irrigations is associated with an increased risk. Rhinologists should be alerted to the potential risks of long-term use of budesonide nasal irrigations, and monitoring for HPAA suppression may be warranted in patients receiving long-term budesonide irrigation therapy. PMID- 26879336 TI - Long-Lived Excited-State Dynamics of i-Motif Structures Probed by Time-Resolved Infrared Spectroscopy. AB - UV-generated excited states of cytosine (C) nucleobases are precursors to mutagenic photoproduct formation. The i-motif formed from C-rich sequences is known to exhibit high yields of long-lived excited states following UV absorption. Here the excited states of several i-motif structures have been characterized following 267 nm laser excitation using time-resolved infrared spectroscopy (TRIR). All structures possess a long-lived excited state of ~300 ps and notably in some cases decays greater than 1 ns are observed. These unusually long-lived lifetimes are attributed to the interdigitated DNA structure which prevents direct base stacking overlap. PMID- 26879337 TI - Characterization of the AXH domain of Ataxin-1 using enhanced sampling and functional mode analysis. AB - Ataxin-1 is the protein responsible for the Spinocerebellar ataxia type 1, an incurable neurodegenerative disease caused by polyglutamine expansion. The AXH domain plays a pivotal role in physiological functions of Ataxin-1. In Spinocerebellar ataxia 1, the AXH domain is involved in the misfolding and aggregation pathway. Here molecular modeling is applied to investigate the protein-protein interactions contributing to the AXH dimer stability. Particular attention is focused on: (i) the characterization of AXH monomer-monomer interface; (ii) the molecular description of the AXH monomer-monomer interaction dynamics. Technically, an approach based on functional mode analysis, here applied to replica exchange molecular dynamics trajectories, was employed. The findings of this study are consistent with previous experimental results and elucidate the pivotal role of the I580 residue in mediating the AXH monomer monomer interaction dynamics. PMID- 26879339 TI - Abnormal Cathodic Photocurrent Generated on an n-Type FeOOH Nanorod-Array Photoelectrode. AB - A simple, wet-chemical method for the synthesis of an FeOOH nanorod-array photoelectrode on fluorine-doped tin oxide (FTO) glass is reported. Nanorods of diameter about 35 nm and length about 300 nm have been vertically grown on an FTO substrate. Upon calcination, the FeOOH phase could be easily converted to a hematite structure while maintaining the shape of the nanorod array. An interesting abnormal cathodic photocurrent is generated on the FeOOH nanorod array photoelectrode under illumination, which is totally different from that obtained on a calcined hematite photoelectrode under the same experimental conditions. The cathodic photocurrent density generated on the FeOOH photoelectrode can also be tuned by applying an electrochemical anodic or cathodic treatment. Detailed analysis has revealed that higher valence state Fe(IV) species in the FeOOH photoelectrode play an important role in sacrificing the photoexcited electrons for generation of the cathodic photocurrent. Comparison between the FeOOH and hematite photoelectrodes allows for a better understanding of the interplay between crystal structure, surface reactions, and photocurrent. The findings on this new abnormal phenomenon could also provide guidance for the design of new types of semiconducting photoelectrochemical devices. PMID- 26879338 TI - The effect of combined treatment with a beta3 AR agonist and a ROCK inhibitor on detrusor overactivity. AB - AIMS: The objective of the study was to evaluate the efficacy and safety of the combined treatment with the beta3 AR agonist and ROCK inhibitor in the rat model of detrusor overactivity induced by retinyl acetate instillation. METHODS: The ROCK inhibitor (GSK 269962) and/or the beta3 AR agonist (BRL 37344) were administered in single doses and a cystometry was carried out, along with a 24 hr measurement of cardiovascular parameters and diuresis. RESULTS: The combined use of GSK 269962 and BRL 37344 in doses ineffective in monotherapies, ameliorated DO. An increase was found in voided volume, voiding efficiency, volume threshold, intercontraction interval, bladder compliance, and volume threshold to elicit nonvoiding contractions, accompanied by a decrease in basal pressure, threshold pressure, detrusor overactivity index, nonvoiding contractions amplitude, and frequency. The combination therapy in question proved to have no effect on micturition voiding pressure, post-void residual, bladder contraction duration, or relaxation time. A 24 hr observation of female rats who received GSK 269962 and/or BRL 37344 did not show any significant changes in urine production. BRL 37344 increased heart rate and blood pressure proportionately to the applied dose. The assessment of the combined treatment with GSK 269962 and BRL 37344 revealed a significant drop of cardiovascular parameters when compared to the rats which only received BRL 37344. DISCUSSION: The combined use of beta3 AR agonists and ROCK inhibitors may improve overactive bladder treatment efficacy and minimize side effects. CONCLUSION: This polytherapy appears to improve urine storage with no impairment of voiding function. Neurourol. Urodynam. 36:580-588, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26879340 TI - TiO2 Nanotubes: Nitrogen-Ion Implantation at Low Dose Provides Noble-Metal-Free Photocatalytic H2 -Evolution Activity. AB - Low-dose nitrogen implantation induces an ion and damage profile in TiO2 nanotubes that leads to "co-catalytic" activity for photocatalytic H2 -evolution (without the use of any noble metal). Ion implantation with adequate parameters creates this active zone limited to the top part of the tubes. The coupling of this top layer and the underlying non-implanted part of the nanotubes additionally contributes to an efficient carrier separation and thus to a significantly enhanced H2 generation. PMID- 26879342 TI - Improved interpretation of studies comparing methods of dietary assessment: combining equivalence testing with the limits of agreement. AB - The aim of this study was to demonstrate the use of testing for equivalence in combination with the Bland and Altman method when assessing agreement between two dietary methods. A sample data set, with eighty subjects simulated from previously published studies, was used to compare a FFQ with three 24 h recalls (24HR) for assessing dietary I intake. The mean I intake using the FFQ was 126.51 (sd 54.06) ug and using the three 24HR was 124.23 (sd 48.62) ug. The bias was 2.28 (sd 43.93) ug with a 90% CI 10.46, 5.89 ug. The limits of agreement (LOA) were -88.38, 83.82 ug. Four equivalence regions were compared. Using the conventional 10 % equivalence range, the methods are shown to be equivalent both by using the CI (-12.4, 12.4 ug) and the two one-sided tests approach (lower t= 2.99 (79 df), P=0.002; upper t=2.06 (79 df), P=0.021). However, we make a case that clinical decision making should be used to set the equivalence limits, and for nutrients where there are potential issues with deficiency or toxicity stricter criteria may be needed. If the equivalence region is lowered to +/-5 ug, or +/- 10 ug, these methods are no longer equivalent, and if a wider limit of +/ 15 ug is accepted they are again equivalent. Using equivalence testing, acceptable agreement must be assessed a priori and justified; this makes the process of defining agreement more transparent and results easier to interpret than relying on the LOA alone. PMID- 26879341 TI - Mapping the neck disability index to SF-6D in patients with chronic neck pain. AB - BACKGROUND: This study sought to statistically map the neck disability index (NDI) to the six-dimension health state short form (SF-6D) to estimate algorithms for use in economic analyses in patients with chronic neck pain (CNP). METHODS: The relationships between NDI and SF-6D scores were estimated by using data from a cohort of patients with chronic neck pain (n = 272). By using ordinary least squares (OLS), generalized linear modeling (GLM), censored least absolute deviations (CLAD) and Tobit regression, scores from all 10 items of the NDI instruments were univariately tested against SF-6D values and retained in a multivariate regression model, if statistically significant. The predictive ability of the model was assessed by mean absolute error (MAE), root mean square error (RMSE) and normalized RMSE. RESULTS: The mean age of the 272 CNP patients was 39.9 +/- 12.3 years; 57.8 % of the CNP patients were female. An OLS regression equation that included recreation item of NDI was optimal, with a MAE of 0.04and 0.04 and an RMSE of 0.06and 0.05in the derivation set and validation set, respectively. Predicted utilities accurately represented the observed ones. CONCLUSIONS: We have provided algorithms for the estimation of health state utility values from the response of NDI. Future economic evaluations of the interventions for chronic neck pain could be informed by these algorithms. PMID- 26879343 TI - 9-Hydroxyrisperidone-Induced Hyperprolactinaemia in Thai Children and Adolescents with Autism Spectrum Disorder. AB - Although our previous study revealed an association between prolactin level and risperidone dosage, data regarding the plasma concentration of risperidone are lacking. Therefore, this study aimed to investigate the association between plasma drug concentrations of risperidone, 9-hydroxyrisperidone and serum prolactin level in Thai children and adolescents with autism spectrum disorder (ASD). The individuals for this study were 103 children and adolescents with ASD (90 males and 13 females). In the 12th hour after the last risperidone dose, blood samples were collected for analysis. Serum prolactin, plasma risperidone and 9-hydroxyrisperidone levels were measured. Patients' clinical data were collected from medical records - age, weight, height, body mass index, dose of risperidone and duration of treatment. Serum prolactin level was significantly positively correlated with plasma 9-hydroxyrisperidone level (rs = 0.355, p < 0.001). The median concentration of 9-hydroxyrisperidone in individuals with hyperprolactinaemia (7.59 ng/ml; IQR 4.86-15.55) was significantly higher than non-hyperprolactinaemic individuals (5.18 ng/ml; IQR 2.10-8.99) after risperidone treatment (p = 0.006). By multivariate analysis, high prolactin level was correlated to high 9-hydroxyrisperidone level (p = 0.010). The results of this study showed that serum prolactin levels, especially in autistic individuals with hyperprolactinaemia during risperidone treatment, were significantly correlated with the level of 9-hydroxyrisperidone. These results suggest that hyperprolactinaemia may develop during risperidone treatment. PMID- 26879344 TI - Anatomy of the true interatrial septum for transseptal access to the left atrium. AB - Clinical anatomy of the interatrial septum is treacherous, difficult and its unfamiliarity can cause many serious complications. This work aims to create an anatomical map of the true interatrial septum. An appreciation of the anatomical situation is essential for safe and efficacious transseptal access from the right atrium to the left heart chambers. Examination of 135 autopsied human hearts (Caucasian) of both sexes (28% females) aged from 19 to 94 years old (47.0+/ 18.2) with BMI=27.1+/-6.0kg/m(2) was conducted. Focus was specifically targeted on the assessment of the fossa ovalis, patent foramen ovale (PFO), and right sided septal pouch (RSP) morphology. Mean values of cranio-caudal and antero posterior fossa ovalis diameters were 12.1+/-3.6 and 14.1+/-3.6mm, respectively. The fossa ovalis was situated an average of 10.1+/-4.4mm above the inferior vena cava ostium, 20.7+/-5.2mm from the right atrioventricular ring, and 12.6+/-5.2mm under the right atrium roof. Four types of fossa ovalis anatomy have been observed (smooth-56.3%, PFO-24.4%, RSP-11.9%, net-like formation-7.4%). The PFO mean channel length was 10.5+/-5.2mm. The tunnel-like PFO (channel length >=12mm) was observed in 8.9% of specimens. The RSP was observed in 11.9% of specimens (with mean depth=6.3+/-3.8mm) and was directed apex upward in all observed specimens (may imitate the PFO channel). The fossa ovalis/interatrial septum surface area ratio was 18.3+/-9.0%. IN CONCLUSION: (1) An anatomical map of the interatrial septum from the right atrial side was presented. (2) The RSP may imitate the PFO channel. (3) The "true" interatrial septum represents only about 20% of the whole interatrial septum area. (4) There is wide variation in the location and geometry of the fossa ovalis. (5) We could distinguish four different types of the fossa ovalis area. PMID- 26879345 TI - Molecular and systems approaches towards drought-tolerant canola crops. AB - 1169 I. 1170 II. 1170 III. 1172 IV. 1176 V. 1181 VI. 1182 1183 References 1183 SUMMARY: Modern agriculture is facing multiple challenges including the necessity for a substantial increase in production to meet the needs of a burgeoning human population. Water shortage is a deleterious consequence of both population growth and climate change and is one of the most severe factors limiting global crop productivity. Brassica species, particularly canola varieties, are cultivated worldwide for edible oil, animal feed, and biodiesel, and suffer dramatic yield loss upon drought stress. The recent release of the Brassica napus genome supplies essential genetic information to facilitate identification of drought related genes and provides new information for agricultural improvement in this species. Here we summarize current knowledge regarding drought responses of canola, including physiological and -omics effects of drought. We further discuss knowledge gained through translational biology based on discoveries in the closely related reference species Arabidopsis thaliana and through genetic strategies such as genome-wide association studies and analysis of natural variation. Knowledge of drought tolerance/resistance responses in canola together with research outcomes arising from new technologies and methodologies will inform novel strategies for improvement of drought tolerance and yield in this and other important crop species. PMID- 26879346 TI - Validation of "laboratory-supported" criteria for functional (psychogenic) tremor. AB - BACKGROUND: In a small group of patients, we have previously shown that a combination of electrophysiological tests was able to distinguish functional (psychogenic) tremor and organic tremor with excellent sensitivity and specificity. OBJECTIVES: This study aims to validate an electrophysiological test battery as a tool to diagnose patients with functional tremor with a "laboratory supported" level of certainty. METHODS: For this prospective data collection study, we recruited 38 new patients with functional tremor (mean age 37.9 +/- 24.5 years; mean disease duration 5.9 +/- 9.0 years) and 73 new patients with organic tremor (mean age 55.4 +/- 25.4 years; mean disease duration 15.8 +/- 17.7 years). Tremor was recorded at rest, posture (with and without loading), action, while performing tapping tasks (1, 3, and 5 Hz), and while performing ballistic movements with the less-affected hand. Electrophysiological tests were performed by raters blinded to the clinical diagnosis. We calculated a sum score for all performed tests (maximum of 10 points) and used a previously suggested cut-off score of 3 points for a diagnosis of laboratory-supported functional tremor. RESULTS: We demonstrated good interrater reliability and test-retest reliability. Patients with functional tremor had a higher average score on the test battery when compared with patients with organic tremor (3.6 +/- 1.4 points vs 1.0 +/- 0.8 points; P < .001), and the predefined cut-off score for laboratory-supported functional tremor yielded a test sensitivity of 89.5% and a specificity of 95.9%. CONCLUSION: We now propose this test battery as the basis of laboratory-supported criteria for the diagnosis of functional tremor, and we encourage its use in clinical and research practice. PMID- 26879348 TI - Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does Not Prevent Vertebral Fractures: Results of a Prospective Observational Cohort Study. AB - OBJECTIVE: Ankylosing spondylitis (AS) is characterized by chronic inflammation leading to ankylosis, but also to low bone mineral density (BMD) and vertebral fractures (VFx). Treatment with tumor necrosis factor-alpha blockers decreases inflammation and has shown to be effective in increasing BMD. We studied the effects of etanercept (ETN) on BMD and VFx in patients with AS after 2 years of treatment. Further, we studied changes in bone turnover markers and radiological damage. METHODS: Patients with active AS, treated with ETN for 2 years, were included. BMD lumbar spine and hip were measured at baseline and after 2 years, as well as radiological damage (modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine), VFx (Genant method), and change in bone turnover markers. RESULTS: Forty-nine patients with AS were included. After 2 years of ETN, hip BMD increased by 2.2% (p = 0.014) and lumbar spine BMD by 7.0% (p < 0.001). The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly (p < 0.001), as well as C-reactive protein and erythrocyte sedimentation rate (p < 0.001). Despite ETN therapy, the number of patients with VFx more than doubled (from 6 to 15 patients, p = 0.003). Also, the radiological damage increased significantly over time (from 12.1 to 18.5, p < 0.001); however, no significant change in bone turnover markers was found. CONCLUSION: This prospective longitudinal observational cohort study showed that after 2 years of ETN, BMD of the hip and spine increased significantly, but the number of patients with VFx and the severity of VFx increased as well. Besides that, radiological progression, including the thoracic spine, increased significantly. Thus, the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage. PMID- 26879347 TI - Fecal prevalence, serotype distribution and antimicrobial resistance of Salmonellae in dairy cattle in central Ethiopia. AB - BACKGROUND: Salmonellae are major worldwide zoonotic pathogens infecting a wide range of vertebrate species including humans. Consumption of contaminated dairy products and contact with dairy cattle represent a common source of non-typhoidal Salmonella infection in humans. Despite a large number of small-scale dairy farms in Addis Ababa and its surrounding districts, little is known about the status of Salmonella in these farms. RESULTS: Salmonella was recovered from the feces of at least one animal in 7.6% (10/132) of the dairy farms. Out of 1203 fecal samples examined, 30 were positive for Salmonella resulting in a weighted animal level prevalence of 2.3%. Detection of diarrhea in an animal and in a farm was significantly associated with animal level (p = 0.012) and herd level (p < 0.001) prevalence of Salmonella. Animal level prevalence of Salmonella was significantly associated with age (p = 0.023) and study location; it was highest among those under 6 months of age and in farms from Adaa district and Addis Ababa (p < 0.001). Nine different serotypes were identified using standard serological agglutination tests. The most frequently recovered serotypes were Salmonella Typhimurium (23.3%), S. Saintpaul (20%), S. Kentucky (16.7%) and S. Virchow (16.7%). All isolates were resistant or intermediately resistant to at least one of the 18 drugs tested. Twenty-six (86.7%), 19 (63.3 %), 18 (60%), 16 (53.3%) of the isolates were resistant to streptomycin, nitrofurantoin, sulfisoxazole and tetracycline , respectively. Resistance to 2 drugs was detected in 27 (90%) of the isolates. Resistance to 3 or more drugs was detected in 21 (70%) of the isolates, while resistance to 7 or more drugs was detected in 11 (36.7%) of the isolates. The rate of occurrence of multi-drug resistance (MDR) in Salmonella strains isolated from dairy farms in Addis Ababa was significantly higher than those isolated from farms outside of Addis Ababa (p = 0.009). MDR was more common in S. Kentucky, S. Virchow and S. Saintpaul. CONCLUSION: Isolation of Salmonella serotypes commonly known for causing human salmonellosis that are associated with an MDR phenotype in dairy farms in close proximity with human population is a major public health concern. These findings imply the need for a strict pathogen reduction strategy. PMID- 26879349 TI - Immunochip Analyses of Epistasis in Rheumatoid Arthritis Confirm Multiple Interactions within MHC and Suggest Novel Non-MHC Epistatic Signals. AB - OBJECTIVE: Studying statistical gene-gene interactions (epistasis) has been limited by the difficulties in performance, both statistically and computationally, in large enough sample numbers to gain sufficient power. Three large Immunochip datasets from cohort samples recruited in the United Kingdom, United States, and Sweden with European ancestry were used to examine epistasis in rheumatoid arthritis (RA). METHODS: A full pairwise search was conducted in the UK cohort using a high-throughput tool and the resultant significant epistatic signals were tested for replication in the United States and Swedish cohorts. A forward selection approach was applied to remove redundant signals, while conditioning on the preidentified additive effects. RESULTS: We detected abundant genome-wide significant (p < 1.0e-13) epistatic signals, all within the MHC region. These signals were reduced substantially, but a proportion remained significant (p < 1.0e-03) in conditional tests. We identified 11 independent epistatic interactions across the entire MHC, each explaining on average 0.12% of the phenotypic variance, nearly all replicated in both replication cohorts. We also identified non-MHC epistatic interactions between RA susceptible loci LOC100506023 and IRF5 with Immunochip-wide significance (p < 1.1e-08) and between 2 neighboring single-nucleotide polymorphism near PTPN22 that were in low linkage disequilibrium with independent interaction (p < 1.0e-05). Both non-MHC epistatic interactions were statistically replicated with a similar interaction pattern in the US cohort only. CONCLUSION: There are multiple but relatively weak interactions independent of the additive effects in RA and a larger sample number is required to confidently assign additional non-MHC epistasis. PMID- 26879350 TI - Assessment of Fatigue in Spondyloarthritis and Its Association with Disease Activity. AB - OBJECTIVE: To evaluate fatigue in patients with spondyloarthritis (SpA) and to define its association with disease-related factors and patients' features. METHODS: A cross-sectional multicenter study which includes 2251 patients with SpA selected from the national Spondyloarthropathies Registry (the Spanish Society of Rheumatology; REGISPONSER) Spanish cohort. The primary outcome was the assessment of fatigue performed with the first item of the Bath Ankylosing Spondyloarthritis Disease Activity Index followed by the study of its relation with different factors organized into 4 groups: sociodemographics, emotional, disease-related, and disease activity. Univariate logistic regressions, multivariate logistic regression, and multiple linear regressions were performed to relate fatigue with the studied covariates. RESULTS: Mean fatigue score in all patients with SpA was 4.3 +/- 2.9, with statistically significant differences between different SpA types. In univariate logistic regressions, significant differences were seen for many variables included in the 4 groups. Multivariate logistic regression showed that high fatigue score was related with sex (female), emotional component, the Ankylosing Spondylitis Quality of Life score, stiffness, and high levels of 2 visual analog scale items (vertebral pain in the last week and patient's global assessment of disease activity). The multivariate linear regression showed that fatigue was mainly explained by disease-related factors and disease activity (54.1%), but sex and emotional status may also be involved in 13.5% of the variance. CONCLUSION: Fatigue is associated with disease-related factors and mostly with SpA activity. However, the emotional component and sex may contribute to the onset of fatigue. PMID- 26879351 TI - Ghost Busting, Taking the Sheet Off the Ghost. PMID- 26879352 TI - Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus. AB - OBJECTIVE: The traditional Framingham Risk Factor Score (FRS) underestimates the risk for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE). We aimed to determine whether an adjustment to the FRS would more accurately reflect the higher prevalence of CAD among patients with SLE. METHODS: Patients with SLE without a previous history of CAD or diabetes followed regularly at the University of Toronto Lupus Clinic were included. A modified FRS (mFRS) was calculated by multiplying the items by 1.5, 2, 3, or 4. In the first part of the study, using one-third of all eligible patients, we evaluated the sensitivity and specificity of the FRS and the different multipliers for the mFRS. In the second part of the study, using the remaining 2/3 of the eligible patients, we compared the predictive ability of the FRS to the mFRS. In the third part of the study, we assessed the prediction for CAD in a time-dependent analysis of the FRS and mFRS. RESULTS: There were 905 women (89.3%) with a total of 95 CAD events included. In part 1, we determined that a multiplier of 2 provided the best combination of sensitivity and specificity. In part 2, 2.4% of the patients were classified as moderate/high risk based on the classic FRS and 17.3% using the 2FRS (the FRS with a multiplier of 2). In part 3, a time dependent covariate analysis for the prediction of the first CAD event revealed an HR of 3.22 (p = 0.07) for the classic FRS and 4.37 (p < 0.0001) for the 2FRS. CONCLUSION: An mFRS in which each item is multiplied by 2 more accurately predicts CAD in patients with SLE. PMID- 26879353 TI - The Longterm Effect of Early Intensive Treatment of Seniors with Rheumatoid Arthritis: A Comparison of 2 Population-based Cohort Studies on Time to Joint Replacement Surgery. AB - OBJECTIVE: Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA). METHOD: Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000-2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated. RESULTS: Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95-0.98) and other DMARD (HR 0.98, 95% CI 0.97 0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2-3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC. CONCLUSION: Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery. PMID- 26879354 TI - The Rate of Adherence to Antiarthritis Medications and Associated Factors among Patients with Rheumatoid Arthritis: A Systematic Literature Review and Metaanalysis. AB - OBJECTIVE: Reported adherence in rheumatoid arthritis (RA) varies widely (10.5 98.5%). Variability may result in part from different methods used to measure adherence. Our aims were to quantify adherence to antiarthritis medications for each method and to identify variability and associated factors. METHODS: The systematic literature review examined PubMed, the Cochrane central database, and article reference lists from 1970 to November 2014. Papers with medication adherence data (disease-modifying antirheumatic drugs, steroids, and nonsteroidal antiinflammatory drugs) in adult patients with RA or data on associated factors were included. Adherence rate was recorded for each method. Random-effect metaanalysis estimated adherence for different evaluation methods. RESULTS: Adherence rate was 66% (95% CI 0.58-0.75). There were no differences in adherence among different measurement methods (interview, questionnaires, etc.). Regression analysis showed that adherence decreases during followup. Among 100 possible factors potentially effecting adherence, 7 adherence-associated factors were found in at least 2 different studies. These were the use of infliximab compared with etanercept or methotrexate (MTX), use of MTX compared to sulfasalazine or to etanercept, belief in the necessity of the medications, older age, and white race. CONCLUSION: Overall adherence rate was 66%. We suggest that readers appraise adherence studies according to the medications evaluated, the validity of the method, and the scales and cutpoints. PMID- 26879355 TI - Early Remission Is a Realistic Target in a Majority of Patients with DMARD-naive Rheumatoid Arthritis. AB - OBJECTIVE: We analyzed remission rates at 3 and 12 months in patients with rheumatoid arthritis (RA) who were naive for disease-modifying antirheumatic drugs (DMARD) and who were treated in a Finnish rheumatology clinic from 2008 to 2011. We compared remission rates and drug treatments between patients with RA and patients with undifferentiated arthritis (UA). METHODS: Data from all DMARD naive RA and UA patients from the healthcare district were collected using software that includes demographic and clinical characteristics, disease activity, medications, and patient-reported outcomes. Our rheumatology clinic applies the treat-to-target principle, electronic monitoring of patients, and multidisciplinary care. RESULTS: Out of 409 patients, 406 had data for classification by the 2010 RA criteria of the American College of Rheumatology/European League Against Rheumatism. A total of 68% were female, and mean age (SD) was 58 (16) years. Respectively, 56%, 60%, and 68% were positive for anticyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), and RF/anti-CCP, and 19% had erosive disease. The median (interquartile range) duration of symptoms was 6 (4-12) months. A total of 310 were classified as RA and 96 as UA. The patients with UA were younger, had better functional status and lower disease activity, and were more often seronegative than the patients with RA. The 28-joint Disease Activity Score (3 variables) remission rates of RA and UA patients at 3 months were 67% and 58% (p = 0.13), and at 12 months, 71% and 79%, respectively (p = 0.16). Sustained remission was observed in 57%/56% of RA/UA patients. Patients with RA used more conventional synthetic DMARD combinations than did patients with UA. None used biological DMARD at 3 months, and only 2.7%/1.1% of the patients (RA/UA) used them at 12 months (p = 0.36). CONCLUSION: Remarkably high remission rates are achievable in real-world DMARD-naive patients with RA or UA. PMID- 26879357 TI - Development of a Rheumatology-specific Patient Concerns Inventory and Its Use in the Rheumatology Outpatient Clinic Setting. AB - OBJECTIVE: Successful management of rheumatic conditions involves increasing complexity of care. Delivering this in a holistic way is a growing challenge. The aim of our study was to develop a Patient Concerns Inventory (PCI) and assess it in the rheumatology clinic setting. METHODS: This observational exploratory study occurred with 2 phases. In phase I, the PCI was developed after a systematic literature search, expert opinion, and 3 patient focus group discussions. In phase II, the PCI was piloted in a general rheumatology clinic. RESULTS: Fifty four patients were assessed in the pre-PCI group and 51 in the post-PCI group. Median (IQR) duration of consultation was 8 min (5-14) without PCI and 15 min (10 20) with PCI. The pre-PCI group raised 335 concerns from 50 patients, median (IQR) of 5 (3-10) per patient, rising post-PCI to 521 concerns, median (IQR) of 9 (5-16) from 51 patients, p = 0.002. Additional concerns predominantly arose from "physical and functional well-being" and "social care and well-being" domains. Most patients rated their experience with their doctor in the consultation as excellent or outstanding across all 11 questions in the questionnaire, both before and after the introduction of the PCI to the clinic setting. CONCLUSION: The PCI is a useful holistic needs assessment tool for rheumatology clinics. Although its use may initially prolong the consultation slightly, patients can raise a significantly higher number of concerns, which does not occur at the expense of patient satisfaction. This may help in identifying areas of unmet needs that previously went unnoticed. PMID- 26879358 TI - Achievement of Remission and Low Disease Activity Definitions in Patients with Rheumatoid Arthritis in Clinical Practice: Results from the NOR-DMARD Study. AB - OBJECTIVE: To examine the frequency of 6 definitions for remission and 4 definitions for low disease activity (LDA) after starting a disease-modifying antirheumatic drug (DMARD) in patients with rheumatoid arthritis (RA) in clinical practice, and to study whether predictors for achieving remission after 6 months are similar for these definitions. METHODS: Remission and LDA were calculated according to the 28-joint Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), the Routine Assessment of Patient Index Data (RAPID3), and both the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Boolean remission definitions 3 and 6 months after 4992 DMARD prescriptions for patients enrolled in the NOR-DMARD, a 5-center Norwegian register. Prediction of remission after 6 months was also studied. RESULTS: After 3 months, remission rates varied between definitions from 8.7% to 22.5% and for LDA from 35.5% to 42.7%, and increased slightly until 6 months of followup. DAS28 and RAPID3 gave the highest and ACR/EULAR, SDAI, and CDAI the lowest proportions for remission. Positive predictors for remission after 6 months were similar across the definitions and included lower age, male sex, short disease duration, high level of education, current nonsmoking, nonerosive disease, treatment with a biological DMARD, being DMARD-naive, good physical function, little fatigue, and LDA. CONCLUSION: In daily clinical practice, the DAS28 and RAPID3 definitions identified remission about twice as often as the ACR/EULAR Boolean, SDAI, and CDAI. Predictors of remission were similar across remission definitions. These findings provide additional evidence to follow treatment recommendations and treat RA early with a DMARD. PMID- 26879356 TI - Phenotypic Characterization of Juvenile Idiopathic Arthritis in African American Children. AB - OBJECTIVE: Juvenile idiopathic arthritis (JIA) affects children of all races. Prior studies suggest that phenotypic features of JIA in African American (AA) children differ from those of non-Hispanic white (NHW) children. We evaluated the phenotypic differences at presentation between AA and NHW children enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and replicated the findings in a JIA cohort from a large center in the southeastern United States. METHODS: Children with JIA enrolled in the multicenter CARRA Registry and from Emory University formed the study and replication cohorts. Phenotypic data on non-Hispanic AA children were compared with NHW children with JIA using the chi-square test, Fisher's exact test, and the Wilcoxon signed-rank test. RESULTS: In all, 4177 NHW and 292 AA JIA cases from the CARRA Registry and 212 NHW and 71 AA cases from Emory were analyzed. AA subjects more often had rheumatoid factor (RF)-positive polyarthritis in both the CARRA (13.4% vs 4.7%, p = 5.3 * 10(-7)) and the Emory (26.8% vs 6.1%, p = 1.1 * 10(-5)) cohorts. AA children had positive tests for RF and cyclic citrullinated peptide antibodies (CCP) more frequently, but oligoarticular or early onset antinuclear antibody (ANA)-positive JIA less frequently in both cohorts. AA children were older at onset in both cohorts and this difference persisted after excluding RF-positive polyarthritis in the CARRA Registry (median age 8.5 vs 5.0 yrs, p = 1.4 * 10( 8)). CONCLUSION: Compared with NHW children, AA children with JIA are more likely to have RF/CCP-positive polyarthritis, are older at disease onset, and less likely to have oligoarticular or ANA-positive, early-onset JIA, suggesting that the JIA phenotype is different in AA children. PMID- 26879359 TI - Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc-positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study. AB - OBJECTIVE: Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis. METHODS: Thirty three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated. RESULTS: None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. CONCLUSION: The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified. PMID- 26879360 TI - How to Motivate Patients with Rheumatoid Arthritis to Quit Smoking. AB - OBJECTIVE: Seropositive rheumatoid arthritis (RA) is strongly linked to cigarette smoking, and smoking cessation is an essential step in RA management. Our objectives were to develop RA and smoking awareness materials and to evaluate the influence of the materials on awareness about the links between RA and smoking and on motivation to quit smoking. METHODS: A group of patients with seropositive RA in Fife, Scotland, were telephoned before the campaign, and the results of the precampaign questionnaire were used to develop the image for the campaign. After the campaign a second group of patients were questioned to ascertain the effect of the campaign. RESULTS: The 320 patient responses to the precampaign questionnaire revealed that many ex-smokers with RA had quit when they developed a known smoking-related disease such as emphysema. This concept was used to develop an image illustrating that RA is a smoking-related disease. The campaign was launched in Fife in 2011. The postcampaign questionnaire involving 380 patients revealed that there was 21% higher awareness of a link between RA and smoking and 45% higher awareness that smoking could interfere with treatment of RA. In total, 13/75 smokers who had cut down since the campaign had been influenced by the new information. CONCLUSION: The new materials have successfully increased patients' knowledge of the link between RA and smoking and the effect of smoking on RA therapy. RA smokers' attitudes to smoking may have been affected by the campaign. PMID- 26879361 TI - Why Do Patients with Chronic Inflammatory Rheumatic Diseases Discontinue Their Biologics? An Assessment of Patients' Adherence Using a Self-report Questionnaire. AB - OBJECTIVE: Concerns have been raised about nonadherence behavior among patients with chronic inflammatory rheumatic diseases (CIRD) receiving biologics. This nonadherence may be caused by various factors. The main objective was to explain why patients discontinue their biologics of their own accord. METHODS: A quantitative and descriptive study was performed using a self-report questionnaire that was sent through the Internet to members of different patient associations. Sociodemographic data, medical and therapeutic history, management of biologic administration, previous experiences, and patients' beliefs and perceptions about treatment efficacy and side effects were studied to explain self-discontinuation (SD). RESULTS: A total of 581 patients answered the questionnaire between June 16, 2012, and July 4, 2012, including patients with ankylosing spondylitis (351/581, 60.4%), rheumatoid arthritis (196/581, 33.7%), psoriatic arthritis (30/581, 5.2%), and other CIRD (4/581, 0.7%). More than 1000 different biologics were described by the 581 patients, with a median of 2 lines per patient. Eighty-six patients discontinued their biologics of their own accord (14.8%). In a multivariate analysis, factors that were significantly related to SD were low level of pain, more than 1 line of biologics tried, self administration of biologics, negative beliefs about the treatment, and a lack of medical and social support. CONCLUSION: Five predictive factors of this SD were identified, which should be assessed in routine with patients with CIRD receiving biologic treatment: pain, treatment history, self-administration of injections, negative beliefs about treatment, and a lack of perceived medical and social support. PMID- 26879362 TI - Effect of Rheumatoid Arthritis on Longterm Sickness Absence in 1994-2011: A Danish Cohort Study. AB - OBJECTIVE: By linkage of national registries, we investigated the risk of longterm sickness absence (LTSA) >= 3 weeks in a large cohort of Danish patients with rheumatoid arthritis (RA) and non-patients. The study aimed to (1) estimate the risk of LTSA for patients with RA compared with the general population, (2) examine whether the risk of LTSA has changed in recent years, and (3) evaluate the effect of other risk factors for LTSA (e.g., physical work demands, age, sex, education, and psychiatric and somatic comorbidities). METHODS: A total of 6677 patients with RA aged 18-59 years in the years 1994-2011 were identified in registries and compared with 56,955 controls from the general population matched by age, sex, and city size. The risk of LTSA was analyzed using Cox proportional hazards models with late entry, controlling for other risk factors and assuming separate risks in the first year after diagnosis and the following years. RESULTS: Compared with the general population, patients with RA had increased risk of LTSA in the first year after diagnosis (HR 5.4 during 1994-1999, 95% CI 4.2-6.8) and in following years (HR 2.4, 95% CI 2.1-2.8). For established RA (> 1 yr after diagnosis), the excess was 20% lower in 2006-2011 (HR 1.9, 95% CI 1.7 2.2) compared with 1994-1999 (p < 0.001). For patients with RA and controls, older age, shorter education, a physically demanding job, and somatic and/or psychiatric comorbidities increased the risk of LTSA. CONCLUSION: While improvements were observed from 1994-1999 to 2006-2011, patients with RA have significant increased risk of LTSA, in particular in the first year after diagnosis. PMID- 26879363 TI - Carotid Atherosclerosis in Adult Patients with Persistently Active Juvenile Idiopathic Arthritis Compared with Healthy Controls. AB - OBJECTIVE: Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease in childhood. It is regarded as a systemic inflammatory disease with possible increased risk of cardiovascular disease (CVD). The aim of this study was to assess carotid intima-media thickness (IMT) and carotid stenosis as surrogate measures for CVD in adults with longterm active JIA and healthy age- and sex-matched controls. METHODS: Seventy-five patients with JIA (age 28-45 yrs) with persistently active disease at least 15 years after disease onset were reexamined after a median of 29 years and compared with 75 matched controls. Patients and controls were examined by color duplex ultrasound of the carotid arteries to compare carotid IMT and carotid stenosis in the 2 groups. RESULTS: Patients with JIA did not have increased carotid IMT values compared with the controls (mean +/- SD: 0.56 mm +/- 0.09 vs 0.58 mm +/- 0.07, p = 0.289). Patients with a higher disease activity indicated by the Juvenile Arthritis Disease Activity Score value above the median value had increased carotid IMT compared with the patients with a lower value, but not statistically different compared with controls. No carotid stenoses were detected in patients or controls. CONCLUSION: We found similar carotid IMT values in adult patients with JIA and controls. PMID- 26879364 TI - Electrochemical Visualization of Intracellular Hydrogen Peroxide at Single Cells. AB - In this Letter, the electrochemical visualization of hydrogen peroxide inside one cell was achieved first using a comprehensive Au-luminol-microelectrode and electrochemiluminescence. The capillary with a tip opening of 1-2 MUm was filled with the mixture of chitosan and luminol, which was coated with the thin layers of polyvinyl chloride/nitrophenyloctyl ether (PVC/NPOE) and gold as the microelectrode. Upon contact with the aqueous hydrogen peroxide, hydrogen peroxide and luminol in contact with the gold layer were oxidized under the positive potential resulting in luminescence for the imaging. Due to the small diameter of the electrode, the microelectrode tip was inserted into one cell and the bright luminescence observed at the tip confirmed the visualization of intracellular hydrogen peroxide. The further coupling of oxidase on the electrode surface could open the field in the electrochemical imaging of intracellular biomolecules at single cells, which benefited the single cell electrochemical detection. PMID- 26879365 TI - Ultrasensitive Detection of Shigella Species in Blood and Stool. AB - A modified immunosensing system with voltage-controlled signal amplification was used to detect Shigella in stool and blood matrixes at the single-digit CFU level. Inactivated Shigella was spiked in these matrixes and detected directly. The detection was completed in 78 min. Detection limits of 21 CFU/mL and 18 CFU/mL were achieved in stool and blood, respectively, corresponding to 2-7 CFUs immobilized on the detecting electrode. The outcome of the detection of extremely low bacterium concentration, i.e., below 100 CFU/mL, blood samples show a random nature. An analysis of the detection probabilities indicates the correlation between the sample volume and the success of detection and suggests that sample volume is critical for ultrasensitive detection of bacteria. The calculated detection limit is qualitatively in agreement with the empirically determined detection limit. The demonstrated ultrasensitive detection of Shigella on the single-digit CFU level suggests the feasibility of the direct detection of the bacterium in the samples without performing a culture. PMID- 26879366 TI - Frequency-Domain Approach To Determine Magnetic Address-Sensor Separation Distance Using the Harmonic Ratio Method. AB - In this work, we describe an approach to determine the distance separating a magnetic address from a scanning magnetoresistive sensor, a critical adjustable parameter for certain bioassay analyses where magnetic nanoparticles are used as labels. Our approach is leveraged from the harmonic ratio method (HRM), a method used in the hard drive industry to control the distance separating a magnetoresistive read head from its data platter with nanometer resolution. At the heart of the HRM is an amplitude comparison of a signal's fundamental frequency to that of its harmonics. When the signal is derived from the magnetic field pattern of a periodic array of magnetic addresses, the harmonic ratio contains the information necessary to determine the separation between the address array and the read head. The elegance of the HRM is that there is no need of additional components to the detection platform to determine a separation distance; the streaming "bit signal" contains all the information needed. In this work, we demonstrate that the tenets governing HRM used in the hard drive industry can be applied to the bioanalytical arena where submicrometer to 100 MUm separations are required. PMID- 26879367 TI - [Cs6 Cl][Fe24 Se26 ]: A Host-Guest Compound with Unique Fe-Se Topology. AB - The novel host-guest compound [Cs6Cl][Fe24Se26] (I4/mmm; a=11.0991(9), c=22.143(2) A) was obtained by reacting Cs2Se,CsCl, Fe, and Se in closed ampoules. This is the first member of a family of compounds with unique Fe-Se topology, which consists of edge-sharing, extended fused cubane [Fe8Se6Se8/3] blocks that host a guest complex ion, [Cs6Cl](5+). Thus Fe is tetrahedrally coordinated and divalent with strong exchange couplings, which results in an ordered antiferromagnetic state below TN =221 K. At low temperatures, a distribution of hyperfine fields in the Mossbauer spectra suggests a structural distortion or a complex spin structure. With its strong Fe-Se covalency, the compound is close to electronic itinerancy and is, therefore, prone to exhibit tunable properties. PMID- 26879369 TI - Erratum to: Differences in TGF-beta1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer. PMID- 26879371 TI - The development and psychometric analysis of the Chinese HIV-Related Fatigue Scale. AB - AIMS AND OBJECTIVES: To develop a Chinese version of the human immunodeficiency virus-related Fatigue Scale and examine its reliability and validity. BACKGROUND: Fatigue is found in more than 70% of people infected with human immunodeficiency virus. However, a scale to assess fatigue in human immunodeficiency virus positive people has not yet been developed for use in Chinese-speaking countries. DESIGN: A methodologic study involving instrument development and psychometric evaluation was used. METHODS: The human immunodeficiency virus-related Fatigue Scale was examined through a two-step procedure: (1) translation and back translation and (2) psychometric analysis. A sample of 142 human immunodeficiency virus-positive patients was recruited from the Infectious Disease Outpatient Clinic in central Taiwan. Their fatigue data were analysed with Cronbach's alpha for internal consistency. Two weeks later, the data of a random sample of 28 patients from the original 142 were analysed for test-retest reliability. The correlation between the World Health Organization Quality of Life Assessment Human Immunodeficiency Virus and the Chinese version of the human immunodeficiency virus-related Fatigue Scale was analysed for concurrent validity. The Chinese version of the human immunodeficiency virus-related Fatigue Scale scores of human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without were compared to demonstrate construct validity. RESULTS: The internal consistency and test-retest reliability of the Chinese version of the human immunodeficiency virus-related Fatigue Scale were 0.97 and 0.686, respectively. In regard to concurrent validity, a negative correlation was found between the scores of the Chinese version of the human immunodeficiency virus-related Fatigue Scale and the World Health Organization Quality of Life Assessment-Human Immunodeficiency Virus. Additionally, the Chinese version of the human immunodeficiency virus-related Fatigue Scale could be used to effectively distinguish fatigue differences between the human immunodeficiency virus-positive patients with highly active antiretroviral therapy and those without. CONCLUSIONS: The Chinese version of the human immunodeficiency virus-related Fatigue Scale presents good reliability and validity through a robust psychometric analysis. This scale can be appropriately applied to human immunodeficiency virus-positive patients by clinical staff and case managers in Chinese-speaking countries. RELEVANCE TO CLINICAL PRACTICE: The Chinese version of the human immunodeficiency virus-related Fatigue Scale is an effective and comprehensive tool that can help clinical professionals measure the frequency, strength and impact on the quality of life of fatigue in Chinese human immunodeficiency virus-positive patients. PMID- 26879368 TI - Synthesis and Applications of (ONO Pincer)Ruthenium-Complex-Bound Norvalines. AB - Two (ONO pincer)ruthenium-complex-bound norvalines, Boc-[Ru(pydc)(terpy)]Nva-OMe (1; Boc=tert-butyloxycarbonyl, terpy=terpyridyl, Nva=norvaline) and Boc [Ru(pydc)(tBu-terpy)]Nva-OMe (5), were successfully synthesized and their molecular structures and absolute configurations were unequivocally determined by single-crystal X-ray diffraction. The robustness of the pincer Ru complexes and norvaline scaffolds against acidic/basic, oxidizing, and high-temperature conditions enabled us to perform selective transformations of the N-Boc and C-OMe termini into various functional groups, such as alkyl amide, alkyl urea, and polyether groups, without the loss of the Ru center or enantiomeric purity. The resulting dialkylated Ru-bound norvaline, n-C11 H23 CO-l-[Ru(pydc)(terpy)]Nva-NH n-C11 H23 (l-4) was found to have excellent self-assembly properties in organic solvents, thereby affording the corresponding supramolecular gels. Ru-bound norvaline l-1 exhibited a higher catalytic activity for the oxidation of alcohols by H2 O2 than parent complex [Ru(pydc)(terpy)] (11 a). PMID- 26879372 TI - Wash-free magnetic immunoassay of the PSA cancer marker using SERS and droplet microfluidics. AB - We report a novel wash-free magnetic immunoassay technique for prostate-specific antigen (PSA) that uses a surface-enhanced Raman scattering (SERS)-based microdroplet sensor. The magnetic bar embedded in a droplet-based microfluidic system segregates the free and bound SERS tags by splitting the droplets into two smaller parts. The presence of PSA targets leads more SERS tags to immunocomplex in one droplet so that fewer SERS tags remain in another supernatant solution droplet. Thus, SERS signal measurement enables the quantitative evaluation of PSA markers. This approach can provide a rapid and sensitive assay that is applicable for PSA cancer markers in serum without any washing. Specifically, SERS signals were measured at 174 droplets per minute and averaged for quantitative evaluation of PSA. The limit of detection (LOD) determined by our SERS-based microdroplet sensor was estimated to be below 0.1 ng mL(-1), which is significantly below the clinical cut-off value for the diagnosis of prostate cancer. In addition, because the entire assay can be carried out automatically, only a minimal amount of sample is needed. Accordingly, the approach is expected to be useful as a potential clinical tool for the early diagnosis of prostate cancer. PMID- 26879370 TI - Systematic data-querying of large pediatric biorepository identifies novel Ehlers Danlos Syndrome variant. AB - BACKGROUND: Ehlers Danlos Syndrome is a rare form of inherited connective tissue disorder, which primarily affects skin, joints, muscle, and blood cells. The current study aimed at finding the mutation that causing EDS type VII C also known as "Dermatosparaxis" in this family. METHODS: Through systematic data querying of the electronic medical records (EMRs) of over 80,000 individuals, we recently identified an EDS family that indicate an autosomal dominant inheritance. The family was consented for genomic analysis of their de-identified data. After a negative screen for known mutations, we performed whole genome sequencing on the male proband, his affected father, and unaffected mother. We filtered the list of non-synonymous variants that are common between the affected individuals. RESULTS: The analysis of non-synonymous variants lead to identifying a novel mutation in the ADAMTSL2 (p. Gly421Ser) gene in the affected individuals. Sanger sequencing confirmed the mutation. CONCLUSION: Our work is significant not only because it sheds new light on the pathophysiology of EDS for the affected family and the field at large, but also because it demonstrates the utility of unbiased large-scale clinical recruitment in deciphering the genetic etiology of rare mendelian diseases. With unbiased large-scale clinical recruitment we strive to sequence as many rare mendelian diseases as possible, and this work in EDS serves as a successful proof of concept to that effect. PMID- 26879373 TI - The optimal sex pheromone release rate for trapping the codling moth Cydia pomonella (Lepidoptera: Tortricidae) in the field. AB - For successful pest management, codlemone (E, E-8,10-dodecadien-1-ol) is widely used to monitor codling moth. The pheromone release rate is essential for the lure's attractiveness. The optimal sex pheromone release rate (V0) for trapping codling moth was evaluated during 2013-2014. The overwinter generation V0 was 6.7 33.4 MUg wk(-1), and moth catches (MCs) were 0.82 +/- 0.11 adults/trap/week; MCs for lower (V1) and higher (V2) release rates were 52.4% and 46.3%, respectively, of that for V0. The first generation V0 was 18.4-29.6 MUg wk(-1), with MCs of 1.45 +/- 0.29 adults/week/trap. V1 and V2 MCs were 34.5% and 31.7%, respectively, of those for V0. Combining across generations, the final V0 was 18.4-29.6 MUg wk( 1), with MCs of 1.07 +/- 0.06 adults/week/trap. V1 and V2 MCs were 51.4% and 41.1%, respectively, of that for V0. Overwinter generation emergence was relatively concentrated, requiring a wider V0. Maintaining the release rate at 18.4-29.6 MUg wk(-1) could optimize the lure's efficacy; this resulted in the capture of nearly 1.9 and 2.4 times more moths than V1 and V2, respectively. The results also indicate that a dispenser pheromone release rate of 200-300 times that of the female moth can perfectly outcompetes females in the field. PMID- 26879374 TI - Abiraterone acetate for metastatic castration-resistant prostate cancer after docetaxel failure: A randomized, double-blind, placebo-controlled phase 3 bridging study. AB - OBJECTIVES: To evaluate the efficacy and safety of abiraterone acetate-prednisone versus placebo-prednisone in Asian metastatic castration-resistant prostate cancer patients who have failed docetaxel-based chemotherapy. METHODS: In this double-blind, phase 3 study from China, 214 patients were randomized (2:1) to abiraterone acetate 1000 mg once daily plus prednisone 5 mg twice daily and placebo plus prednisone 5 mg twice daily in 28-day treatment cycles. RESULTS: Abiraterone acetate-prednisone treatment significantly decreased prostate specific antigen progression risk by 49%, with longer median time to prostate specific antigen progression of 5.55 months versus 2.76 months in the placebo prednisone group (hazard ratio 0.506, P = 0.0001, primary end-point). There was a strong trend for improved overall survival in the abiraterone acetate-prednisone group, with a 40% decrease in the risk of death (hazard ratio 0.604, P = 0.0597); however, median survival was not reached in either group because of the short follow-up period (12.9 months) and limited number of observed death events. The prostate-specific antigen response rate was higher in the abiraterone-prednisone group (49.7%) than in the placebo-prednisone group (14.1%). A total of 37.1% patients in this group had pain progression events compared with 50.7% in the placebo-prednisone group. Abiraterone-prednisone significantly decreased the risk of pain progression by 50% (hazard ratio 0.496, P = 0.0014). The incidence of adverse events was similar between the two groups; the most common adverse events being anemia (25.9% for abiraterone-prednisone vs 22.5% for placebo-prednisone), hypokalemia (25.9% and 11.3%), bone pain (23.8% and 21.1%), hypertension (16.1% and 12.7%) and increased aspartate aminotransferase (14.7% and 15.5%), respectively. CONCLUSIONS: Abiraterone-prednisone significantly delays disease and pain progression, and prostate-specific antigen, with a favorable benefit risk ratio in Asian metastatic castration-resistant prostate cancer patients in the post-docetaxel setting. PMID- 26879376 TI - Biodegradable Inorganic Nanovector: Passive versus Active Tumor Targeting in siRNA Transportation. AB - The biodegradable inorganic nanovector based on a layered double hydroxide (LDH) holds great promise for gene and drug delivery systems. However, in vivo targeted delivery of genes through LDH still remains a key challenge in the development of RNA interference therapeutics. Here, we describe in vivo and in vitro delivery system for Survivin siRNA (siSurvivin) assembled with passive LDH with a particle size of 100 nm or active LDH conjugated with a cancer overexpressing receptor targeting ligand, folic acid (LDHFA), conferring them an ability to target the tumor by either EPR-based clathrin-mediated or folate receptor-mediated endocytosis. When not only transfected into KB cells but also injected into xenograft mice, LDHFA/siSurvivin induced potent gene silencing at mRNA and protein levels in vitro, and consequently achieved a 3.0-fold higher suppression of tumor volume than LDH/siSurvivin in vivo. This anti-tumor effect was attributed to a selectively 1.2-fold higher accumulation of siSurvivin in tumor tissue compared with other organs. Targeting to the tumor with inorganic nanovector can guide and accelerate an evolution of next-generation theranosis system. PMID- 26879375 TI - Hydrogen sulfide promotes angiogenesis by downregulating miR-640 via the VEGFR2/mTOR pathway. AB - We previously found hydrogen sulfide (H2S) to be a new proangiogenic factor. However, the mechanisms underlying the cardiovascular effect of this small gas molecule remain largely unknown. The aim of the present study was to identify the essential microRNAs (miRNAs) involved in the transduction of H2S signals in vascular endothelial cells (ECs). The expression of miR-640 and its signaling elements, vascular endothelial growth factor receptor 2 (VEGFR2), hypoxia inducible factor 1-alpha (HIF1A), and mammalian target of rapamycin (mTOR), was measured using quantitative PCR and Western blotting. Overexpression and inhibition of miR-640 were performed to clarify their roles in mediating the effect of H2S. In addition, knockdown of VEGFR2, HIF1A, and mTOR was performed using siRNAs, dominant negative mutants, or inhibitors to examine their roles in the transduction of the H2S signals. miR-640 levels decreased in vascular ECs that were treated with H2S, whereas overexpression of miR-640 blunted the proangiogenic effect of H2S. Knockdown of either VEGFR2 or mTOR blunted the downregulation of miR-640 and the proangiogenic effect induced by H2S. In addition, miR-640 bound to the 3'-UTR of HIF1A mRNA and then inhibited the expression of HIF1A. The inhibition could be recovered by treating cells with H2S. Thus we concluded that miR-640 plays a pivotal role in mediating the proangiogenic effect of H2S; H2S acts through downregulation of the expression of miR-640 and increasing the levels of HIF1A through the VEGFR2-mTOR pathway. PMID- 26879377 TI - FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome. AB - Dyslipidemia is common in polycystic ovary syndrome (PCOS). This study was aimed to investigate whether fatty acid desaturase genes (FADS), a dyslipidemia-related gene cluster, are associated with PCOS. We scanned variations of FADS genes using our previous data of genome-wide association study (GWAS) for PCOS and selected rs174570 for further study. The case-control study was conducted in an independent cohort of 1918 PCOS cases and 1889 age-matched controls and family based study was conducted in a set of 243 core family trios with PCOS probands. Minor allele frequency (allele T) of rs174570 was significantly lower in PCOS cases than that in age-matched controls (P = 2.17E-03, OR = 0.85), even after adjustment of BMI and age. PCOS subjects carrying CC genotype had higher testosterone level and similar lipid/glucose level compared with those carrying TT or TC genotype. In trios, transmission disequilibrium test (TDT) analysis revealed risk allele C of rs174570 was significantly over-transmitted (P = 2.00E 04). Decreased expression of FADS2 was detected in PCOS cases and expression quantitative trait loci (eQTL) analysis revealed the risk allele C dosage was correlated with the decline of FADS2 expression (P = 0.002). Our results demonstrate that FADS1-FADS2 are susceptibility genes for PCOS. PMID- 26879379 TI - Prevalence of chlamydia among HIV positive and HIV negative patients in the Vhembe District as detected by real time PCR from urine samples. AB - BACKGROUND: Chlamydia is a bacterial infection that has long plagued humanity as the most commonly contracted STD and is caused by Chlamydia trachomatis. With the emergence of HIV/AIDS, sexually transmitted diseases have also re-emerged as a grave public health problem, particularly in developing countries. Updated Information about the relative frequencies in developing countries is sparse. This study aims at establishing the relative occurrence of chlamydia using real time PCR technique in the Vhembe District of South Africa where reports on the prevalence of chlamydia are not available. METHODS: A total of 243 Urine samples were collected from patients attending different ARV clinics in the Vhembe District and genomic DNA was purified using blood genomic DNA kit from Sigma Aldrich. Real-Time PCR protocol targeting the 16S rRNA gene of C. trachomatis was used to confirm the presence of chlamydia among these patients. Demographic information as well as clinical data was collected as well. RESULTS: Of all the participants, 70.4% were females. The age varied from 19 to 72 years. The overall prevalence of chlamydia was 32.1%. The prevalence was significantly higher among females (39.2%) compared to males (15.5%) patients (P = 0.001) and was highest among pregnant women followed by patients who had reported any allergic reaction. Among the HIV positive patients, the prevalence was higher among those who were not taking ARV (38.1%) compared to those who were taking them (28.5%). The age group within which the highest prevalence was found was between 26-45 years. CONCLUSIONS: The present study shows a high prevalence of chlamydia among HIV and AIDS patients in the Vhembe District emphasizing the need to enhance STI control and particularly chlamydia among all young people. The particularly high prevalence of chlamydia among pregnant women is of great concern as this predisposes them to complications, while allergy migh predispose people to chlamydia infections. Further studies are needed in the general population both HIV positive and HIV negative persons to further determine the impact of these infections in the community. PMID- 26879378 TI - Increased availability of NADH in metabolically engineered baker's yeast improves transaminase-oxidoreductase coupled asymmetric whole-cell bioconversion. AB - BACKGROUND: Saccharomyces cerevisiae can be engineered to perform a multitude of different chemical reactions that are not programmed in its original genetic code. It has a large potential to function as whole-cell biocatalyst for one-pot multistep synthesis of various organic molecules, and it may thus serve as a powerful alternative or complement to traditional organic synthetic routes for new chemical entities (NCEs). However, although the selectivity in many cases is high, the catalytic activity is often low which results in low space-time-yields. In the case for NADH-dependent heterologous reductive reactions, a possible constraint is the availability of cytosolic NADH, which may be limited due to competition with native oxidative enzymes that act to maintain redox homeostasis. In this study, the effect of increasing the availability of cytosolic NADH on the catalytic activity of engineered yeast for transamination-reduction coupled asymmetric one-pot conversion was investigated. RESULTS: A series of active whole cell biocatalysts were constructed by over-expressing the (S)-selective omega transaminase (VAMT) from Capsicum chinense together with the NADH-dependent (S) selective alcohol dehydrogenase (SADH) originating from Rhodococcus erythropolis in strains with or without deletion of glycerol-3-phosphate dehydrogenases 1 and 2 (GPD1 and GPD2). The yeast strains were evaluated as catalysts for simultaneous: (a) kinetic resolution of the racemic mixture to (R)-1 phenylethylamine, and (b) reduction of the produced acetophenone to (S)-1 phenylethanol. For the gpd1Deltagpd2Delta strain, cell metabolism was effectively used for the supply of both amine acceptors and the co-factor pyridoxal-5' phosphate (PLP) for the omega-transaminase, as well as for regenerating NADH for the reduction. In contrast, there was nearly no formation of (S)-1-phenylethanol when using the control strain with intact GPDs and over-expressing the VAMT-SADH coupling. It was found that a gpd1Deltagpd2Delta strain over-expressing SADH had a 3-fold higher reduction rate and a 3-fold lower glucose requirement than the strain with intact GPDs over-expressing SADH. CONCLUSIONS: Overall the results demonstrate that the deletion of the GPD1 and GPD2 genes significantly increases activity of the whole-cell biocatalyst, and at the same time reduces the co substrate demand in a process configuration where only yeast and sugar is added to drive the reactions, i.e. without addition of external co-factors or prosthetic groups. PMID- 26879380 TI - Molecular rheology of neuronal membranes explored using a molecular rotor: Implications for receptor function. AB - The role of membrane cholesterol as a crucial regulator in the structure and function of membrane proteins and receptors is well documented. However, there is a lack of consensus on the mechanism for such regulation. We have previously shown that the function of an important neuronal receptor, the serotonin1A receptor, is modulated by cholesterol in hippocampal membranes. With an overall objective of addressing the role of membrane physical properties in receptor function, we measured the viscosity of hippocampal membranes of varying cholesterol content using a meso-substituted fluorophore (BODIPY-C12) based on the BODIPY probe. BODIPY-C12 acts as a fluorescent molecular rotor and allows measurement of hippocampal membrane viscosity through its characteristic viscosity-sensitive fluorescence depolarization. A striking feature of our results is that specific agonist binding by the serotonin1A receptor exhibits close correlation with hippocampal membrane viscosity, implying the importance of global membrane properties in receptor function. We envision that our results are important in understanding GPCR regulation by the membrane environment, and is relevant in the context of diseases in which GPCR signaling plays a major role and are characterized by altered membrane fluidity. PMID- 26879381 TI - Nitropyrrole natural products: isolation, biosynthesis and total synthesis. AB - Nitropyrrole-containing natural products are relatively rare in nature. Known examples are limited to the beta-nitropyrrole-containing pyrrolomycins and alpha nitropyrrole-containing nitropyrrolins and heronapyrroles. Their unique structures and interesting bioactivity are of ongoing interest to the chemistry community. This review describes the isolation, biological activity, biosynthesis and chemical synthesis of nitropyrrole-containing natural products reported to date. PMID- 26879382 TI - JAZF1/SUZ12 gene fusion in endometrial stromal sarcomas. AB - Endometrial stromal sarcomas (ESSs) belong to the rarest uterine malignancies (prevalence category <1-9/1,000,000). According to the new 2014 World Health Organisation (WHO) classification, they are separated into four categories; benign endometrial stromal nodules (ESNs), low grade endometrial stromal sarcomas (LG-ESSs), high-grade endometrial stromal sarcomas (HG-ESSs) and undifferentiated uterine sarcomas (UUSs). Due to heterogeneous histopathologic appearance these tumors still represent diagnostic challenge, even for experienced pathologists. ESSs are genetically very heterogeneous and several chromosomal translocations and gene fusions have so far been identified in these malignancies. To date the JAZF1/SUZ12 gene fusion is by far the most frequent and seems to be the cytogenetic hallmark of ESN and LG-ESS. Based on present literature data this gene fusion is present in approximately 75% of ESN, 50% of LG-ESS and 15% of HG ESS cases. The frequency of JAZF1/SUZ12 appearance varies between classic ESS and different morphologic variants. This gene fusion is suggested to become a specific diagnostic tool, especially in difficult borderline cases. In combination with the recently described YWHAE/FAM22 gene fusion the JAZF1/SUZ12 fusion could be used to differentiate between LG-ESS and HG-ESS. The purpose of this review is to summarize literature data published in last two and a half decades about this gene fusion, as a contribution to our understanding of ESS genetics and pathogenesis. PMID- 26879383 TI - Conformational Flexibility of a Short Loop near the Active Site of the SARS 3CLpro is Essential to Maintain Catalytic Activity. AB - The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 3(10)-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 3(10)-helix and helps to stabilize the active conformation. The coil-3(10)-helix conformational transition of the Ser139 Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations. PMID- 26879384 TI - Prevalence and trend of neural tube defects in five counties in Shanxi province of Northern China, 2000 to 2014. AB - BACKGROUND: The prevalence of neural tube defects (NTDs) in northern China is among the highest in the world. A massive folic acid supplementation program as a specific countermeasure was introduced in 2009. Examining trends in NTD prevalence may provide evidence for future intervention. METHODS: Data for 2000 to 2014 in five counties in northern China were obtained through a population based birth defects surveillance system. All live births, stillbirths of over 20 gestational weeks, and pregnancy terminations because of NTDs at any gestational age were recorded. The prevalence of NTDs by gestational weeks (< 28 vs. >= 28), by calendar year, and by subtype was presented. RESULTS: From 2000 to 2014, a total of 234,225 births and 2027 cases of NTDs were recorded. The prevalence of total NTDs was extremely high during 2000 to 2004, but it began to decrease continuously thereafter, from a peak of 120.0/10,000 in 2004 to a low of 31.5/10,000 in 2014. A significant decrease (60%) was observed from 78.8/10,000 in 2009 to 31.5/10,000 in 2014, 5 years after the folic acid supplementation program was introduced. All three major subtypes, namely anencephaly, spina bifida, and encephalocele, showed a decline over this period. Although the perinatal (>= 28 gestational weeks) prevalence of NTDs decreased progressively, the pre-perinatal (< 28 gestational weeks) prevalence of NTDs remained high until 2011 and then decreased. CONCLUSION: The prevalence of NTDs remains high despite a substantial and continuous decrease over the past 15 years. To further reduce NTD risk in the population, fortification staples with folic acid should be considered. PMID- 26879386 TI - Visualizing the orientational dependence of an intermolecular potential. AB - Scanning probe microscopy can now be used to map the properties of single molecules with intramolecular precision by functionalization of the apex of the scanning probe tip with a single atom or molecule. Here we report on the mapping of the three-dimensional potential between fullerene (C60) molecules in different relative orientations, with sub-Angstrom resolution, using dynamic force microscopy (DFM). We introduce a visualization method which is capable of directly imaging the variation in equilibrium binding energy of different molecular orientations. We model the interaction using both a simple approach based around analytical Lennard-Jones potentials, and with dispersion-force corrected density functional theory (DFT), and show that the positional variation in the binding energy between the molecules is dominated by the onset of repulsive interactions. Our modelling suggests that variations in the dispersion interaction are masked by repulsive interactions even at displacements significantly larger than the equilibrium intermolecular separation. PMID- 26879387 TI - Digoxin reduces atherosclerosis in apolipoprotein E-deficient mice. AB - BACKGROUND AND PURPOSE: Numerous in vitro studies have suggested that digoxin suppresses inflammation and alters lipid metabolism. However, the effect of dioxin on atherosclerosis is poorly understood. The present study was conducted to determine whether digoxin affects the development of atherosclerosis in a murine model of atherosclerotic disease. EXPERIMENTAL APPROACH: Apolipoprotein E deficient mice maintained on a Western-type diet were administered PBS (control), low-dose digoxin (1 mg . kg(-1) . day(-1)) or high-dose digoxin (2 mg . kg(-1) . day(-1)) via i.p. injection for 12 weeks. KEY RESULTS: Digoxin dose-dependently reduced atherosclerotic lesion formation and plasma lipid levels (reductions of 41% in total cholesterol, 54% in triglycerides and 20% in low-density lipoprotein cholesterol in the high-dose digoxin-treated group). Moreover, treatment with digoxin markedly attenuated IL-17A expression and IL-17A-related inflammatory responses and increased the abundance of regulatory T cells (Tregs). CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that digoxin acts as a specific antagonist of retinoid-related orphan receptor-gamma to decrease atherosclerosis by suppressing lipid levels and IL-17A-related inflammatory responses. PMID- 26879388 TI - Nonsteroidal anti-inflammatory administration and patent ductus arteriosus ligation, a survey of practice preferences at US children's hospitals. AB - We surveyed neonatal leadership at 46 US children's hospitals via web-based survey to identify local preferences and concerns regarding indomethacin prophylaxis, nonsteroidal anti-inflammatory drug (NSAID) treatment, and patent ductus arteriosus (PDA) ligation. We received a 100 % survey response (N = 46). Practice guidelines for prophylactic indomethacin were reported at 28 % of NICUs, for NSAID treatment of PDA at 39 % and for surgical ligation at 27 %. Respondents noted intra-institutional practice variation for indomethacin prophylaxis (33 %), NSAID treatment (70 %), and PDA ligation (73 %). The majority of institutions did not prescribe indomethacin prophylaxis (72 %). For PDA treatment, indomethacin was preferred over ibuprofen (80 %). We validated our survey results via comparison with billing data as documented in the Pediatric Health Information System (PHIS) database, finding that survey responses directly correlated with local billing data (p < 0.0001). At institutions that did not typically administer NSAIDs for PDA closure or surgical PDA ligation, a lack of evidence for their effectiveness in improving long-term outcomes and the risk of treatment associated adverse effects were the most often cited reasons. CONCLUSION: No consensus exists among providers at US children's hospitals regarding prophylactic indomethacin, NSAID treatment, or PDA ligation. Lack of evidence and safety concerns play a prominent role. WHAT IS KNOWN: * NSAIDs and surgical PDA ligation are efficacious in preventing intraventricular hemorrhage (IVH) and closing PDA in preterm infants, but have not been shown to improve long-term respiratory, neurodevelopmental, or mortality outcomes. What is New: * Practice preferences for indomethacin prophylaxis, NSAID, and surgical PDA treatment vary both among and within institutions. Lack of treatment effectiveness and the risk of adverse effects are major concerns. PMID- 26879389 TI - Baroreflex Activation Therapy in Heart Failure With Reduced Ejection Fraction: Available Data and Future Perspective. AB - Progression of heart failure with reduced ejection fraction (HFrEF) is promoted by sympathovagal imbalance. Baroreflex activation therapy, i.e., electrical stimulation of baroreceptors at the carotid sinus, can restore sympathovagal balance. Large animal studies of baroreflex activation therapy revealed improvements in cardiac function, susceptibility to ventricular arrhythmias, and a survival benefit as compared to untreated controls. Recently, the first randomized and controlled trial of optimal medical and device therapy alone or plus baroreflex activation therapy in patients suffering from HFrEF was published. It demonstrated a reasonable safety profile in this severely ill patient population. Moreover, the study found significant improvements in New York Heart Association class, quality of life, 6-min walk distance, and NT-proBNP levels. This review provides an overview on baroreflex activation therapy for the treatment of HFrEF-from the concept and preclinical findings to most recent clinical data and upcoming trials. PMID- 26879390 TI - How to Approach the Assessment of Cardiac Allograft Vasculopathy in the Modern Era: Review of Invasive Imaging Modalities. AB - Heart transplantation is one of the most definitive therapies for end-stage heart failure. The therapy is unfortunately marred by the devastating complications of cardiac allograft vasculopathy (CAV). Non-invasive screening and assessment for CAV has been greatly limited by both low sensitivity and poor correlation with adverse outcomes. As such, invasive imaging with coronary angiography has emerged as the gold standard for detection of CAV. Although conventional coronary angiography serves well for larger lesions, the modality has been significantly enhanced with adjunct imaging to visualize the intimal hyperplasia that is a hallmark of the disease process. These modalities include intravascular ultrasound (IVUS) and optical coherence tomography (OCT). In the following review, we summarize both the invasive and non-invasive assessments of CAV. We further conclude that the current evidence poorly supports the use of non invasive testing for early CAV and that a transition should be considered to routine early angiography with adjunctive intravascular imaging. PMID- 26879391 TI - Nonadherence in the Advanced Heart Failure Population. AB - The number of patients living with heart failure (HF) in the USA now exceeds 5 million. Although HF is a disease readily treated by medications and lifestyle interventions, nonadherence is common, leading to worse clinical outcomes and increased healthcare costs. While adherence to medical therapy and clinician recommendations is key in the management of HF, it is perhaps more critical in patients with the most advanced disease, including those receiving home inotropic infusion, heart transplantation, or a left ventricular assist device. Yet, there is a paucity of data on the effects of nonadherence on the advanced heart failure population and little information on the most effective management strategies in these patients. Future studies of nonadherence in HF should utilize uniform definitions of adherence and, ideally, more objective measurements of adherence such as the novel "digital pill" technology. PMID- 26879393 TI - Holey graphene frameworks for highly selective post-combustion carbon capture. AB - Atmospheric CO2 concentrations continue to rise rapidly in response to increased combustion of fossil fuels, contributing to global climate change. In order to mitigate the effects of global warming, development of new materials for cost effective and energy-efficient CO2 capture is critically important. Graphene based porous materials are an emerging class of solid adsorbents for selectively removing CO2 from flue gases. Herein, we report a simple and scalable approach to produce three-dimensional holey graphene frameworks with tunable porosity and pore geometry, and demonstrate their application as high-performance CO2 adsorbents. These holey graphene macrostructures exhibit a significantly improved specific surface area and pore volume compared to their pristine counterparts, and can be effectively used in post-combustion CO2 adsorption systems because of their intrinsic hydrophobicity together with good gravimetric storage capacities, rapid removal capabilities, superior cycling stabilities, and moderate initial isosteric heats. In addition, an exceptionally high CO2 over N2 selectivity can be achieved under conditions relevant to capture from the dry exhaust gas stream of a coal burning power plant, suggesting the possibility of recovering highly pure CO2 for long-term sequestration and/or utilization for downstream applications. PMID- 26879392 TI - Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART. AB - We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/MUL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol. PMID- 26879394 TI - Congenital macrothrombocytopenia-linked mutations in the actin-binding domain of alpha-actinin-1 enhance F-actin association. AB - Mutations in the actin cross-linking protein actinin-1 were recently linked to dominantly inherited congenital macrothrombocytopenia. Here, we report that several disease-associated mutations that are located within the actinin-1 actin binding domain cause increased binding of actinin-1 to actin filaments and enhance filament bundling in vitro. These actinin-1 mutants are also more stably associated with the cytoskeleton in cultured cells, as assessed by biochemical fractionation and fluorescence recovery after photobleaching experiments. For two mutations the disruption of contacts between the calponin homology domains within the actinin actin-binding domain may explain increased filament binding- providing mechanistic and structural insights into the basis of actinin-1 dysfunction in congenital macrothrombocytopenia. PMID- 26879395 TI - Salvage total laryngectomy after external-beam radiotherapy: A 20-year experience. AB - BACKGROUND: The purpose of this study was to present our evaluation of the clinical and functional outcomes after salvage total laryngectomy (STL). METHODS: We conducted a retrospective review of 218 patients who underwent STL between 1994 and 2014. RESULTS: Seventy percent of patients originally had T1 or T2, N0 tumors and 73% had definitive external-beam radiotherapy (EBRT) alone. A majority utilized tracheoesophageal prosthesis (77%) and were gastrostomy free (80%) at last follow-up. The 5-year disease control and overall survival (OS) rates were 65% and 57%, respectively. Patients with a disease-free interval after initial treatment <2 years were more likely to develop a recurrence (p = .001) and die of disease (p = .032) after STL. The disease-free interval after EBRT impacted disease control (p < .001), with 5-year disease control of 92% for >5-year disease-free interval and 60% for <2-year disease-free interval. CONCLUSION: Most patients remain disease-free after STL, achieve intelligible tracheoesophageal speech, and maintain an oral diet. Delayed recurrence after initial treatment portends better survival and may indicate a distinct biological profile. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1962-E1968, 2016. PMID- 26879396 TI - Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders. AB - INTRODUCTION: Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain cases genotype-phenotype correlations are important for predicting the clinical course of the disease and to allow tailor-made follow-up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next-generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost. AIM: The aim of this study was to design and to analyse the applicability of a 23-gene NGS panel in the molecular diagnosis of patients with IBCDs. METHODS: A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology. RESULTS: In all patients, our NGS approach detected causative mutations. Twenty-one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant. CONCLUSION: Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs. PMID- 26879399 TI - Cleft-related nose deformation evaluation and measurement methods. Literature review. AB - INTRODUCTION: Rhinoplasty for the cleft lip and palate patient is very challenging and surgical outcome of the nose is difficult to evaluate. Discussions of aesthetic evaluation of the nose in cleft lip and palate patients remain problematical. Many different nose aesthetic evaluation methods have been described in the literature; they differ even among articles published in a single year. AIM: To analyse the literature concerning aesthetic evaluation of the nose in cleft lip and palate patients and to identify the most objective method for such evaluation postoperatively. MATERIAL AND METHODS: The literature was reviewed using MedLine and PubMed sources dated between January 1996 and December 2014. In total, 118 full text articles in English language were selected. Exclusion criteria were: case reports, surgical reviews, literature review, and single evaluations of nasal function. RESULTS: Measurements were obtained from two-dimensional images in 73 articles. Noses were evaluated from 3D images in 22 and by clinical examination in 15. Other methods were evaluation from dental/facial casts, cephalometric evaluation, computer tomography and video recording. In 26 articles some combination of methods was used. CONCLUSIONS: The most popular evaluation method is still two-dimensional photography and measurements using anthropometric facial landmarks. Measurements from three dimensional images seem to be the most objective method and automated facial anthropometric landmark protraction seems to hold promise for the future. PMID- 26879397 TI - Detection of Merkel Cell Polyomavirus and Human Papillomavirus in Esophageal Squamous Cell Carcinomas and Non-Cancerous Esophageal Samples in Northern Iran. AB - Human papillomavirus (HPV) infection is one of the hypothesized causes of esophageal squamous cell carcinoma (ESCC), but the etiological association remains uncertain. It was postulated that other infectious agents together with HPV may increase the risk of ESCC. The current investigation aimed to explore the presence of a new human tumor virus, Merkel cell polyomavirus (MCPyV), together with HPV in ESCC tumors and non-cancerous esophageal samples in northern Iran. In total, 96 esophageal samples (51 with ESCC, and 45 without esophageal malignancy) were examined. HPV DNA was detected in esophageal specimens of 16 out of the 51 ESCC cases (31.4 %) and 20 out of the 45 non-cancerous samples (44.4 %). Untypable HPV genotypes were recognized in high rates in cancerous (75.0 %) and non-cancerous (55.0 %) esophageal specimens. MCPyV DNA was detected in esophageal specimens of 23 out of the 51 ESCC cases (45.1 %) and 16 out of the 45 non cancerous samples (35.6 %). The mean MCPyV DNA copy number was 1.0 * 10(-5) +/- 2.4 * 10(-5) and 6.0 * 10(-6) +/- 1.3 * 10(-5) per cell in ESCC cases and non cancerous samples, respectively. There was no statistically significant difference between cancerous and non-cancerous samples regarding mean MCPyV DNA load (P = 0.353). A bayesian logistic regression model adjusted to the location of esophageal specimen and MCPyV infection, revealed a significant association between HPV and odds of ESCC (OR, 2.45; 95 % CI: 1.01-6.16). This study provides the evidence of the detection of the MCPyV DNA at a low viral copy number in cancerous and non- cancerous esophageal samples. PMID- 26879398 TI - Application of a novel phosphinothricin N-acetyltransferase (RePAT) gene in developing glufosinate-resistant rice. AB - Currently, only few glufosinate-resistant genes are available for commercial application. Thus, developing novel glufosinate-resistant genes with commercial feasibility is extremely important and urgent for agricultural production. In this study, we transferred a newly isolated RePAT gene into a japonica rice variety Zhonghua11, resulting in a large number of independent T0 transgenic plants, most of which grew normally under high-concentration glufosinate treatment. Four transgenic plants with one intact RePAT expression cassette integrated into the intergenic region were selected. Agronomic performances of their T2 progenies were investigated, and the results suggested that the expression of RePAT had no adverse effect on the agronomic performance. Definite glufosinate resistance of the selected transgenic plants was further confirmed to be related to the expression of RePAT by assay on the medium and qRT-PCR. The inheritance and expression of RePAT in two transgenic plants were confirmed to be stable. Finally, the two-year field assay of glufosinate resistance suggested that the agronomic performance of the transgenic plant (PAT11) was not affected by high dosage of glufosinate (5000 g/ha). Collectively, our study proves the high resistance of a novel gene RePAT to glufosinate and provides a glufosiante resistant rice variety with agricultural application potential. PMID- 26879400 TI - Neuromuscular evaluation in young patients with unilateral posterior crossbite before and after rapid maxillary expansion. AB - OBJECTIVES: The aim of this study is to analyze the electromyographic and electrognatographic exams of 55 patients before and after rapid palatal expansion, and to find out a relationship between the results. MATERIALS AND METHODS: The sample consisted of 55 children (28 females and 27 males; age ranging between 6 and10 years) with unilateral posterior crossbite, and subjected to an electromyographic and electrognatographic examination before and after a rapid palatal expansion. RESULTS: By analyzing the results, it is possible to observe an increased electrical activity of the masticatory muscles (right and left masseters and anterior temporalis) both in rest position and during activities after rapid palatal expansion. CONCLUSIONS: Rapid palatal expansion produces important changes in the muscular tone and it increases the muscular activity of the masticatory muscles. PMID- 26879401 TI - Medication--related osteonecrosis of the jaws. The first reported cases in the Baltic States and a literature review. AB - INTRODUCTION: Medication-related osteonecrosis of the jaws (MRONJ) is a severe side effect of antiresorptive or antiangiogenic therapy that manifests as an exposed bone, accompanied by clinical signs of infection, persisting for more than 8 weeks, without history of radiation therapy or metastases to the jaws. The aim of the study was to present first MRONJ cases in Lithuania and review trends in the modern research literature on the subject. MATERIALS AND METHODS: We retrospectively reviewed patient charts with a diagnosis of "Inflammatory conditions of the jaws" treated in Vilnius University Hospital Zalgiris Clinic, Department of maxillofacial surgery in 2007-2014. Patients diagnosed with MRONJ were selected for the study. Demographic data, characteristics of the disease and treatment modalities were analysed. RESULTS: Nine cases (five male and four female) of MRONJ were analysed. The mean patient age was 69+/-7,9 years. Predominant primary malignancy was prostate cancer. Osteonecrotic lesions were located both in maxilla and mandible. In all cases we started with a conservative treatment first. After the antibiotic therapy with or without sequestrectomy, the condition of all patients stabilized and improved to stage I MRONJ. CONCLUSION: MRONJ is a disturbing condition resulting in a severely worsened quality of life in the affected patients. This is the first case series of successfully treated patients suffering from stage II or III MRONJ in the Baltic States. A more comprehensive understanding of MRONJ will hopefully allow clinicians to enhance accuracy in risk assessment and forecast positive and negative outcomes of antiresorptive or antiangiogenic therapy. PMID- 26879402 TI - Synovial chondromatosis in the temporomandibular joint: case report with review of the literature. AB - Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare benign condition characterized by the formation of metaplastic cartilage in the synovium resulting in numerous attached and unattached osteocartilagenous (calcified) loose bodies within the joint. The purpose of this article is to present a case of SC of the TMJ and to discuss current diagnostic approaches, treatment options and relevant follow-up data. We present a case of SC in the TMJ that was confirmed by histopathological analysis and treated via arthrotomy, and present the typical imaging findings, including Computed Tomography (CT) and orthopantomography (OPTG) findings. PMID- 26879403 TI - Trichoadenoma of the upper lip. AB - BACKGROUND: Trichoadenoma of Nikolowski, who describe the first cases in 1958, is a rare and benign tumor of the hair follicle. It is well-differentiated and slowly-growing. The clinical appearance of Trichoadenoma (TA) can be similar to basal cell carcinoma or epidermal cyst. RESULTS: We describe a 44-year-old male who was referred for nodular lesion on the upper lip and a TA was diagnosed. Oral examination showed exophytic yellow mass located between mucous membrane of the upper lip and vestibular gingiva, 1.2 per 0.8 cm. Anamnestic data was non contributory. An excisional biopsy of the lesion was performed. Microscopically, the lesion consisted of multiple keratinous cysts lined with stratified squamous epithelium and intermingled with solid islands of basaloid cells lying within sclerotic stroma. The pathological diagnosis was TA. The surgical wound healed uneventfully. CONCLUSION: Because the lesion is unique, it is uncertain how aggressive or indolent the tumor might be. Therefore, the microscopical analysis is mandatory. At the best of our knowledge, this is the second case of trichoadenoma of the lip. PMID- 26879405 TI - DDB2 (damaged-DNA binding 2) protein: a new modulator of nanomechanical properties and cell adhesion of breast cancer cells. AB - DDB2, known for its role in DNA repair, was recently shown to reduce mammary tumor invasiveness by inducing the transcription of IkappaBalpha, an inhibitor of NF-kappaB activity. Since cellular adhesion is a key event during the epithelial to mesenchymal transition (EMT) leading to the invasive capacities of breast tumor cells, the aim of this study was to investigate the role of DDB2 in this process. Thus, using low and high DDB2-expressing MDA-MB231 and MCF7 cells, respectively, in which DDB2 expression was modulated experimentally, we showed that DDB2 overexpression was associated with a decrease of adhesion abilities on glass and plastic areas of breast cancer cells. Then, we investigated cell nanomechanical properties by atomic force microscopy (AFM). Our results revealed significant changes in the Young's Modulus value and the adhesion force in MDA MB231 and MCF7 cells, whether DDB2 was expressed or not. The cell stiffness decrease observed in MDA-MB231 and MCF7 expressing DDB2 was correlated with a loss of the cortical actin-cytoskeleton staining. To understand how DDB2 regulates these processes, an adhesion-related gene PCR-Array was performed. Several adhesion-related genes were differentially expressed according to DDB2 expression, indicating that important changes are occurring at the molecular level. Thus, this work demonstrates that AFM technology is an important tool to follow cellular changes during tumorigenesis. Moreover, our data revealed that DDB2 is involved in early events occurring during metastatic progression of breast cancer cells and will contribute to define this protein as a new marker of metastatic progression in this type of cancer. PMID- 26879404 TI - BATMAN-TCM: a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine. AB - Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM's diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients' target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ's cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the "multi-component, multi-target and multi-pathway" combinational therapeutic mechanism of TCM, and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM's molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm. PMID- 26879406 TI - Parallel worlds? French and anglophone perspectives on health geography. AB - In this short commentary, we address the following question: setting aside the issue of translation, do health geographers in France speak the same language as their English-speaking counterparts in various parts of the world? Specifically, do they have comparable empirical, theoretical and political concerns? We briefly survey the 'states of knowledge' in both fields for points of difference and similarity. We devote particular attention to the diverse contexts in which health geography is practiced. Our overarching goal is not to oppose two 'blocks'; nor is it to produce syntheses of two bodies of work. Rather, we seek to identify the diverse contexts in which geographic knowledge of health issues is produced, and to encourage reflection on what these mean for current and future collaboration across linguistic boundaries. We contend that meaningful Anglo-French comparative work will need to be particularly attentive to takes on theory that is 'the same, but different', to alternative spatial lenses (territory vs. place), and to sometimes sharply distinct perspectives on social difference. PMID- 26879407 TI - Cultural carrying capacity: Organ donation advocacy, discursive framing, and social media engagement. AB - Social media sites such as Facebook have become a powerful tool for public health outreach because they enable advocacy organizations to influence the rapidly increasing number of people who frequent these forums. Yet the very open-ness of social media sites creates fierce competition for public attention. The vast majority of social media messages provoke little or no reaction because of the sheer volume of information that confronts the typical social media user each day. In this article, I present a theory of the "cultural carrying capacity" of social media messaging campaigns. I argue that advocacy organizations inspire more endorsements, comments, and shares by social media users if they diversify the discursive content of their messages. Yet too much diversification creates large, disconnected audiences that lack the sense of shared purpose necessary to sustain an online movement. To evaluate this theory, I created a Facebook application that collects social media posts produced by forty-two organ donation advocacy organizations over 1.5 years, as well as supplemental information about the organization, its audience, and the broader social context in which they interact. Time series models provide strong evidence for my theory net of demographic characteristics of social media users, the resources and tactics of each organization, and broader external factors. I conclude by discussing the implications of these findings for public health, cultural sociology, and the nascent field of computational social science. PMID- 26879409 TI - Understanding the anion-pi interactions with tetraoxacalix[2]arene[2]triazine. AB - Anion-pi interaction is a new type of non-covalent interaction. It has attracted growing interest in recent years both theoretically and experimentally. However, the nature of bonding between an anion and an electron-deficient aromatic system has remained elusive. To understand the bonding nature in depth, we have carried out a systematic computational study, using model systems that involve tetraoxacalix[2]arene[2]triazine 1, an electron-deficient macrocyclic host, and four anions, X(-) (X(-) = SCN(-), NO3(-), BF4(-), and PF6(-)), of varied sizes and shapes. The geometries for the 1.X(-) complexes were optimized using the extended ONIOM (XO) method. The good agreements with the X-ray experimental results provide a validation of our theoretical schemes. The nature of the non covalent interactions was analyzed with the help of the AIM (atoms in molecules), RDG (reduced density gradient) and LMO-EDA (local molecular orbital-energy decomposition analysis) methods. The results clearly reveal the involvement of anion-pi bonding, as well as a weak, yet significant, hydrogen bonding interaction between the benzene C-H on 1 and the anion of NO3(-) or PF6(-). The bonding energies of 1.X(-) were calculated with the XYG3 functional, and the results were compared with those from MP2, M06-2X and some other functionals with non-covalent interaction corrections (e.g., B3LYP-D3, and omegaB97X-D). We conclude that the binding strengths follow the order of 1.NO3(-) > 1.SCN(-) > 1.BF4(-) > 1.PF6(-), where the difference between 1.SCN(-) and 1.BF4(-) is less significant. The strongest interaction in 1.NO3(-) comes from: (1) the effective electronic interaction between NO3(-) and the triazine rings on 1; and (2) the weak hydrogen bonding interaction between the benzene C-H on 1 and nitrate, which cooperates with the anion-pi interactions. PMID- 26879408 TI - Does bendamustine impact the mobilization of peripheral blood stem cells? A multicenter retrospective study of 23 cases. AB - Bendamustine is used in the treatment of different relapsing or refractory subtypes of lymphoma. Its impact on the yield of peripheral blood stem cells is not well known. Twenty three patients who received bendamustine followed immediately or after another chemotherapy by stem cell mobilization (SCM) were included. The patients were divided into two groups: group 1 (n=17), in whom SCM was performed immediately after bendamustine chemotherapy, and group 2 (n=6), in whom SCM was performed after another cycle of chemotherapy. The success rate of mobilization after Bendamustine+/-plerixafor was 36% (eight cytapheresis succeeded for a total number of 22 cytapheresis); and 75% after other approaches (chemotherapy based or steady state) used for patients who received bendamustine previously. Although bendamustine used alone was not an effective drug to mobilize stem cells, this agent does not seem to have detrimental effects on subsequent SCM. PMID- 26879410 TI - Mannitol has a protective effect on testicular torsion: An experimental rat model. AB - OBJECTIVE: Testicular torsion is an emergency condition that causes testicular injury. Any treatment opportunity reducing the destructive effect of testicular torsion is important for the future life of patients. In this experimental study we investigated the protective effect of mannitol on ischemia-reperfusion (I/R) injury in a rat testes torsion model. METHOD: In total, 32 male Sprague Dawley rats were included. Four experimental groups included eight rats each. Group A was a sham group in which the right testis was brought out through a scrotal incision and then replaced in the scrotum without torsion. In Group B, the right testis was torsioned, by rotating 720 degrees clockwise and fixed to the scrotum with no treatment. In Group C, the same testicular torsion process was performed with saline infusion just after testicular torsion. In group D, mannitol infusion was used just after testicular torsion. Testicles were detorsioned after 3 h and left inside for more than 2 h before orchiectomy. Histopathological, immunohistochemical, and biochemical analyses were performed. RESULTS: Testicular architecture was disturbed significantly in the torsion groups without mannitol infusion. However, testicular tissue structure was significantly better in the mannitol-treated group, demonstrating a protective effect. Similar findings were also shown for the proliferating cell nuclear antigen (PCNA) index and antioxidant activity; both were higher in the mannitol group than in the no treatment and saline groups (p < 0.01). The apoptotic index was also significantly lower in the mannitol-treated group compared with the no treatment and saline groups (p < 0.01). CONCLUSIONS: The seminiferous tubule structure in testicular torsion without mannitol treatment was significantly disturbed, whereas the structural disruption was considerably less in the mannitol group. Mannitol treatment also decreased reactive oxygen radical levels significantly and was able to decrease apoptosis. These results were consistent with other organ model studies that evaluated the protective effects of mannitol treatment in I/R injury. Mannitol infusion had a protective effect against I/R injury in testicular torsion in rats. This experimental study may guide clinicians to evaluate the effectiveness of mannitol in human testicular torsion. PMID- 26879411 TI - Temporary re-catheterization as a treatment for early fistulas after hypospadias repair. AB - OBJECTIVE: To present the results of temporary urethral re-catheterization in order to aid spontaneous closure of early fistulas after hypospadias repair. METHODS AND TECHNIQUE: Children presenting with early fistulas (within 2 weeks of initial catheter removal) after hypospadias repair underwent urethral calibration and re-insertion of a urethral catheter under intravenous anesthesia. The catheter was removed after 2 weeks. RESULTS: Nine children (age 1-9 years) with early fistulas had re-catheterization: six (66%) had spontaneous healing of the fistula by 2 weeks, which remained closed at subsequent follow-up. CONCLUSION: The simple technique of urethral re-catheterization may allow spontaneous healing of some early fistulas after hypospadias repair. PMID- 26879414 TI - The Feasibility and Effectiveness of Online Guided Imagery Training for Health Professionals. AB - This study evaluated the feasibility and impact of brief online guided imagery training (up to 3 hours) for health professionals. Paired t tests were used to measure pre-to-post-training changes in stress (Perceived Stress Scale,), anxiety (Patient Reported Outcomes Measurement Information System-Anxiety Scale), empathy (Empathic Concern Scale, and Perspective-taking Scale), and self-efficacy (Self Efficacy in providing Non-Drug Therapies Scale). Online guided imagery training attracted diverse health professionals and trainees (n = 273; 14% trainees; 34% registered nurses, 20% physicians, 14% social workers, 5% registered dititians, and 27% others). Participants reported small but significant pre-to-post-module improvements in stress (17.8 to 13.5), anxiety (T-scores 56.4 to 54.3), empathy (both empathic concern, 29.8 to 30.7, and perspective taking, 28.0 to 29.4), and self-efficacy in providing nondrug therapies for common symptoms (58.5 to 77.0) (P < .001 for all). Future studies will need to examine the clinical impact of online guided imagery training for health professionals. PMID- 26879415 TI - Field measurements and analyses of environmental vibrations induced by high-speed Maglev. AB - Maglev, offers competitive journey-times compared to the railway and subway systems in markets for which distance between the stations is 100-1600km owing to its high acceleration and speed; however, such systems may have excessive vibration. Field measurements of Maglev train-induced vibrations were therefore performed on the world's first commercial Maglev line in Shanghai, China. Seven test sections along the line were selected according to the operating conditions, covering speeds from 150 to 430km/h. Acceleration responses of bridge pier and nearby ground were measured in three directions and analyzed in both the time and frequency domain. The effects of Maglev train speed on vibrations of the bridge pier and ground were studied in terms of their peak accelerations. Attenuation of ground vibration was investigated up to 30m from the track centerline. Effects of guideway configuration were also analyzed based on the measurements through two different test sections with same train speed of 300km/h. The results showed that peak accelerations exhibited a strong correlation with both train speed and distance off the track. Guideway configuration had a significant effect on transverse vibration, but a weak impact on vertical and longitudinal vibrations of both bridge pier and ground. Statistics indicated that, contrary to the commonly accepted theory and experience, vertical vibration is not always dominant: transverse and longitudinal vibrations should also be considered, particularly near turns in the track. Moreover, measurements of ground vibration induced by traditional high-speed railway train were carried out with the same testing devices in Bengbu in the Anhui Province. Results showed that the Maglev train generates significantly different vibration signatures as compared to the traditional high-speed train. The results obtained from this paper can provide good insights on the impact of Maglev system on the urban environment and the quality of human life nearby. PMID- 26879412 TI - Phytohormone pathways as targets of pathogens to facilitate infection. AB - Plants are constantly threatened by potential pathogens. In order to optimize the output of defense against pathogens with distinct lifestyles, plants depend on hormonal networks to fine-tune specific responses and regulate growth-defense tradeoffs. To counteract, pathogens have evolved various strategies to disturb hormonal homeostasis and facilitate infection. Many pathogens synthesize plant hormones; more importantly, toxins and effectors are produced to manipulate hormonal crosstalk. Accumulating evidence has shown that pathogens exert extensive effects on plant hormone pathways not only to defeat immunity, but also modify habitat structure, optimize nutrient acquisition, and facilitate pathogen dissemination. In this review, we summarize mechanisms by which a wide array of pathogens gain benefits from manipulating plant hormone pathways. PMID- 26879413 TI - Rice OsVAMP714, a membrane-trafficking protein localized to the chloroplast and vacuolar membrane, is involved in resistance to rice blast disease. AB - Membrane trafficking plays pivotal roles in many cellular processes including plant immunity. Here, we report the characterization of OsVAMP714, an intracellular SNARE protein, focusing on its role in resistance to rice blast disease caused by the fungal pathogen Magnaporthe oryzae. Disease resistance tests using OsVAMP714 knockdown and overexpressing rice plants demonstrated the involvement of OsVAMP714 in blast resistance. The overexpression of OsVAMP7111, whose product is highly homologous to OsVAMP714, did not enhance blast resistance to rice, implying a potential specificity of OsVAMP714 to blast resistance. OsVAMP714 was localized to the chloroplast in mesophyll cells and to the cellular periphery in epidermal cells of transgenic rice plant leaves. We showed that chloroplast localization is critical for the normal OsVAMP714 functioning in blast resistance by analyzing the rice plants overexpressing OsVAMP714 mutants whose products did not localize in the chloroplast. We also found that OsVAMP714 was located in the vacuolar membrane surrounding the invasive hyphae of M. oryzae. Furthermore, we showed that OsVAMP714 overexpression promotes leaf sheath elongation and that the first 19 amino acids, which are highly conserved between animal and plant VAMP7 proteins, are crucial for normal rice plant growths. Our studies imply that the OsVAMP714-mediated trafficking pathway plays an important role in rice blast resistance as well as in the vegetative growth of rice. PMID- 26879416 TI - Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma. AB - OBJECTIVE: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT). METHODS: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis. RESULTS: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS. CONCLUSIONS: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes. PMID- 26879417 TI - A model for assuring clamping success during laparoscopic partial nephrectomy with segmental renal artery clamping. AB - OBJECTIVES: A model for assuring clamping success was established for laparoscopic partial nephrectomy (LPN) with segmental renal artery clamping (SRAC). MATERIALS AND METHODS: Patients (n = 107; December 2009-September 2011) who underwent LPN with SRAC dependent on the experience of the surgeon and CTA were retrospectively reviewed to determine the optimal characteristics of target arteries. After multiple logistic regression analysis, variables used to build a nomogram were selected using a backward elimination scheme. A model for a clamping program customized to the patient was designed. The surgical outcomes of patients (n = 141; October 2011-June 2014) who subsequently underwent LPN-SRAC with the applied model were compared with those of the first group of patients. RESULTS: Five potential predictors were initially assessed: segmental renal artery angle, target artery diameter, and distance (d) to the abdominal aorta, renal hilum (d RH), and kidney midline (d KML). The regression equation was set up as: [Formula: see text]Comparing the patient groups, those for whom the new SRAC model was applied had a significantly better success rate of clamping (P < 0.001), less total operative time (P < 0.001), and less operative blood loss (P = 0.042). No obvious differences were observed in time of warm ischemia, postoperative hospitalization, RENAL nephrometry score, or number of final clamped branches. CONCLUSIONS: The model for assuring clamping success was helpful in designing an SRAC program and thus benefiting the LPN procedure. PMID- 26879419 TI - Piloting Virtual Surgical Patient Cases with 3rd-year medical students during the surgery rotation. AB - BACKGROUND: Surgical education programs are increasingly challenged to make medical students' learning experiences in their surgery rotation meaningful while making the most of limited faculty resources and maximizing patient safety. Simulations and virtual environments are potential resources for providing meaningful clinical learning experiences. METHODS: Ninety-eight 3rd-year medical students used the Virtual Surgical Patient Cases software as a part of their surgery clerkship. We used a mixed-methods approach to data collection and analyses to investigate how students and faculty engaged with cases as teaching and learning tools. RESULTS: Students improved their clinical reasoning skills significantly at each case attempt, but made some errors consistently across attempts. Faculty used the information provided about students' decisions during the cases to guide their teaching during case discussions. CONCLUSIONS: Including more cases in the surgical clerkship could allow students additional practice with making diagnoses and facilitate an interactive role in discussing cases with faculty. PMID- 26879418 TI - Identifying the broken heart: predictors of mortality and morbidity in suspected blunt cardiac injury. AB - BACKGROUND: Blunt cardiac injury (BCI) is an infrequent but potentially fatal finding in thoracic trauma. Its clinical presentation is highly variable and patient characteristics and injury pattern have never been described in trauma patients. The aim of this study was to identify predictors of mortality in BCI patients. METHODS: We performed an 8-year retrospective analysis of all trauma patients diagnosed with BCI at our Level 1 trauma center. Patients older than 18 years, blunt chest trauma, and a suspected diagnosis of BCI were included. BCI was diagnosed based on the presence of electrocardiography (EKG), echocardiography, biochemical cardiac markers, and/or radionuclide imaging studies. Elevated troponin I was defined as more than 2 recordings of greater than or equal to .2. Abnormal EKG findings were defined as the presence of bundle branch block, ST segment, and t-wave abnormalities. Univariate and multivariate regression analyses were performed. RESULTS: A total of 117 patients with BCI were identified. The mean age was 51 +/- 22 years, 65% were male, mean systolic blood pressure was 93 +/- 65, and overall mortality rate was 44%. Patients who died were more likely to have a lactate greater than 2.5 (68% vs 31%, P = .02), hypotension (systolic blood pressure < 90) (86% vs 14%, P = .001), and elevated troponin I (86% vs 11%, P = .01). There was no difference in the rib fracture (58% vs 56%, P = .8), sternal fracture (11% vs 21%, P = .2), and abnormal EKG (89% vs 90%, P = .6) findings. Hypotension and lactate greater than 2.5 were the strongest predictors of mortality in BCI. CONCLUSIONS: BCI remains an important diagnostic and management challenge. However, once diagnosed resuscitative therapy focused on correction of hypotension and lactate may prove beneficial. Although the role of troponin in diagnosing BCI remains controversial, elevated troponin may have prognostic significance. PMID- 26879420 TI - Design and synthesis of pyridazinone-substituted benzenesulphonylurea derivatives as anti-hyperglycaemic agents and inhibitors of aldose reductase - an enzyme embroiled in diabetic complications. AB - Thirty new aryl-pyridazinone-substituted benzenesulphonylurea derivatives (I-XXX) were synthesized and evaluated for their anti-hyperglycaemic activity in glucose fed hyperglycaemic normal rats. Twenty-three compounds (III-XI, XIV-XVII, XIX XXIV, XXVI and XXVIII-XXX) showed more or comparable area under the curve (AUC) reduction percentage (ranging from 21.9% to 35.5%) as compared to the standard drug gliclazide (22.0%). On the basis of docking results, 18 compounds were screened for their in vitro ability to inhibit rat lens aldose reductase. Ten compounds (III-VI, XII, XVI-XVIII, XXI and XXVII) showed ARI activity with IC50 ranging from 34 to 242 MUM. Out of these, two compounds IV and V showed best ARI activity which is comparable with that of quercetin. As a result, two compounds (IV and V) possessing significant dual action (anti-hyperglycaemic and aldose reductase inhibition) were identified and may be used as lead compounds for developing new drugs. PMID- 26879421 TI - Schizophrenia-Associated hERG channel Kv11.1-3.1 Exhibits a Unique Trafficking Deficit that is Rescued Through Proteasome Inhibition for High Throughput Screening. AB - The primate-specific brain voltage-gated potassium channel isoform Kv11.1-3.1 has been identified as a novel therapeutic target for the treatment of schizophrenia. While this ether-a-go-go related K(+)channel has shown clinical relevance, drug discovery efforts have been hampered due to low and inconsistent activity in cell based assays. This poor activity is hypothesized to result from poor trafficking via the lack of an intact channel-stabilizing Per-Ant-Sim (PAS) domain. Here we characterize Kv11.1-3.1 cellular localization and show decreased channel expression and cell surface trafficking relative to the PAS-domain containing major isoform, Kv11.1-1A. Using small molecule inhibition of proteasome degradation, cellular expression and plasma membrane trafficking are rescued. These findings implicate the importance of the unfolded-protein response and endoplasmic reticulum associated degradation pathways in the expression and regulation of this schizophrenia risk factor. Utilizing this identified phenomenon, an electrophysiological and high throughput in-vitro fluorescent assay platform has been developed for drug discovery in order to explore a potentially new class of cognitive therapeutics. PMID- 26879422 TI - Clinical and pathologic considerations of the qualitative and quantitative aspects of lupus nephritogenic autoantibodies: A comprehensive review. AB - Autoantibodies are key mediators in determining the clinical manifestations of systemic lupus erythematosus (SLE). The mechanisms by which antibodies may be harmful to self tissues encompass complement mediated inflammation, cell apoptosis and immune-complexes mediated damage, however the precise cooperation of antibodies in SLE have not been unravelled so far. Lupus nephritis (LN) is a protean feature of SLE resulting in wide variety of symptoms including asymptomatic proteinuria, mild renal disease until end-stage renal failure which are triggered by complex autoantibody interactions. Novel clues concerning development and self-maintenance of LN have come to light in recent times, pointing straight to a multistep inflammatory process which is incited by anti chromatin antibodies, the best known being anti-DNA and anti-nucleosome antibodies, culminating in a self-maintaining inflammatory loop with spreading of glomerular inflammation. In the maintenance of the inflammatory process pro inflammatory antibodies are involved, among which anti-C1q are thought to play a major role, whereas hindrance of the nephritic process could be actively mediated by protective autoantibodies. Despite being so relevant in occurrence of LN, nor anti-chromatin neither anti-C1q antibodies have been precisely characterized in terms of origin, antigen specificity and mechanisms of action. Moreover, novel autoantibodies are emerging in LN which can modify disease course, whereas the pathogenic value of a myriad of cross-reactive antibodies has been progressively challenged. The aim of this review is to give a comprehensive view of known and emerging autoantibody reactivities involved in renal inflammation and damage going over their origin, mechanisms of action and interactions in determining LN course. PMID- 26879423 TI - Exploration of the serum metabolite signature in patients with rheumatoid arthritis using gas chromatography-mass spectrometry. AB - Rheumatoid arthritis (RA) is a systemic autoimmune disease with complicated pathogeny. There could be obvious alterations of metabolism in the patients with RA and the discovery of metabolic signature may be helpful for the accurate diagnosis of RA. In order to explore the distinctive metabolic patterns in RA patients, a gas chromatography-mass spectrometry (GC-MS) method was employed. Serum samples from 33 RA patients and 32 healthy controls were collected and analyzed. Acquired metabolic data were assessed by the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the data analysis results showed RA patients and healthy controls have very different metabolic profiles. Variable importance for project values (VIP) and Student's t test were combined to screen the significant metabolic changes caused by RA. Serums from RA patients were featured by decreased levels of amino acids and glucose, increased levels of fatty acids and cholesterol, which were primarily associated with glycolytic pathway, fatty acid and amino acid metabolism, and other related pathways including TCA cycle and the urea cycle. These preliminary results suggest that GC-MS based metabolic profiling study appears to be a useful tool in the exploration of the metabolic signature of RA, and the revealed disease-associated metabolic perturbations could help to elucidate the pathogenesis of RA and provide a probable aid for the accurate diagnosis of RA. PMID- 26879424 TI - Increasing conclusiveness of clinical breath analysis by improved baseline correction of multi capillary column - ion mobility spectrometry (MCC-IMS) data. AB - Current challenges of clinical breath analysis include large data size and non clinically relevant variations observed in exhaled breath measurements, which should be urgently addressed with competent scientific data tools. In this study, three different baseline correction methods are evaluated within a previously developed data size reduction strategy for multi capillary column - ion mobility spectrometry (MCC-IMS) datasets. Introduced for the first time in breath data analysis, the Top-hat method is presented as the optimum baseline correction method. A refined data size reduction strategy is employed in the analysis of a large breathomic dataset on a healthy and respiratory disease population. New insights into MCC-IMS spectra differences associated with respiratory diseases are provided, demonstrating the additional value of the refined data analysis strategy in clinical breath analysis. PMID- 26879425 TI - [Consensus of Chinese experts on detection of related drive genes in target therapy of non-small cell lung cancer]. PMID- 26879426 TI - [Diffuse large B-cell lymphoma with aberrant expression of CD56: a clinicopathologic and immunohistochemical study]. AB - OBJECTIVE: To study the clinicopathologic features and significance of aberrant CD56 expression in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical and pathologic profiles of 10 cases of DLBCL with aberrant expression of CD56 were investigated. Immunohistochemical staining, in-situ hybridization for Epstein-Barr virus encoded RNA and gene rearrangement for IgH and Igkappa were carried out. RESULTS: There were 6 male and 4 female patients. The medium age of patients was 46 years. All of them presented with extranodal lymphoma involvement, with gastrointestinal tract being the commonest site (5/10). Histologic examination showed that most of the atypical lymphoid cells were centroblast-like and demonstrated a diffuse growth pattern. Apoptosis and necrosis were identified in some cases. Immunohistochemical study showed that the tumor cells were positive for CD20 or CD79alpha and aberrantly expressed CD56. Five cases had the GCB phenotype while the remaining cases had the non-GCB phenotype, according to Hans classification. Bcl-6 was positive in most cases (9/10). All cases showed a high proliferation index by Ki-67. The tumor cells were negative for CD3epsilon, CD138 and granzyme B. In-situ hybridization for Epstein-Barr virus encoded RNA was performed in 7 cases and none of them showed positive signals. IgH gene rearranged bands were detected in 4 cases (4/6) and Igkappa was detected in 3 cases (3/6). Follow-up data were available in 8 patients. Two patients died of disease progression within 5 to 13 months after diagnosis and the other 6 patients were alive 8 to 60 months after therapy. CONCLUSIONS: DLBCL with aberrant expression of CD56 is rare. Most of them present with extranodal involvement, show high frequency of bcl-6 expression and high proliferation index. The patients often have good response to chemotherapy. PMID- 26879427 TI - [Expression and significance of HGAL and LMO2 in follicular lymphoma]. AB - OBJECTIVE: To evaluate the diagnostic value of HGAL and LMO2 expression and compare with CD10 and bcl-6 in follicular lymphoma (FL). METHODS: 63 cases of FL were collected from Guangdong General Hospital. The expression of HGAL, LMO2, CD10 and bcl-6 was assessed by immunohistochemistry. RESULTS: The expression rates of HGAL, LMO2, CD10 and bcl-6 were 98.4% (62/63), 82.5% (52/63), 82.5% (52/63) and 87.3% (55/63), respectively. The expression rate of HGAL was higher than those of LMO2, CD10 and bcl-6, but the differences were not significant (P>0.05). There was no significant difference in HGAL, LMO2 and bcl-6 expression among FL1, FL2 and FL3 cases. The CD10 expression rate of FL1-3A cases was significantly higher than that of FL3B cases(P<0.01). CONCLUSIONS: HGAL and LMO2, especially HGAL, can be used in FL particularly high grade FL as useful germinal center marker. PMID- 26879428 TI - [Clinicopathologic characteristics and immunophenotypes of histiocytic necrotizing lymphadenitis: an analysis of 84 cases]. AB - OBJECTIVE: To study the clinical manifestation, pathologic features and immunophenotype of histiocytic necrotizing lymphadenitis (HNL). METHODS: The clinicopathologic data of 84 patients with HNL from 2005 to 2014 were retrospectively studied. Immunohistochemical staining using EliVision method for CD20, PAX5, CD3, CD45RO, CD4, CD8, CD56, CD68, CD123, granzyme-B, TIA1 and MPO was carried out. In-situ hybridization for Epstein-Barr virus RNA was performed on archival lymph node biopsy tissue. RESULTS: Immunohistochemical study showed that the lesional cells were predominantly histiocytes (CD68+), plasmacytoid dendritic cells (CD123+) and T lymphocytes (CD3+ and CD45RO+). Clusters of CD68 positive cells with strong and diffuse MPO expression were identified. T lymphocytes with CD4 and CD8 positivity were noted. CD56+ natural killer cells and CD20+/PAX5 B cells were rare. Apoptosis-related markers, including TIA1 and granzyme B were expressed by T lymphocytes and histiocytes in lymph nodes of HNL. In-situ hybridization for Epstein-Barr virus RNA was positive in only 10.0% of the cases. CONCLUSIONS: HNL shows no specific clinical and laboratory findings. Recognition of the characteristic histopathologic changes in lymph node biopsy of HNL is the key to correct diagnosis. Immunohistochemical study using a panel of markers, including CD3, CD4, CD8, MPO, CD123, granzyme-B and TIA1, is helpful in the differential diagnosis of HNL. PMID- 26879429 TI - [Post-transplant kidney from C-III donation after cardiac death of children: a clinicopathologic study of 20 cases]. AB - OBJECTIVE: To study the clinical and histopathologic features of post-transplant kidney biopsy tissues from pediatric C-III donors. METHODS: The clinical and pathologic features of 20 cases (22 case-times) of renal transplant biopsies from pediatric cadaveric donors were analyzed by light microscopy and immunohistochemistry according to the Banff system of working classification of renal allograft pathology. Biopsies were compared to those from adult C-III donors and adult cadaveric donors. RESULTS: Sixteen cases (72.7%) showed renal allograft drug toxicity damage by Tacrolimus, seven cases (31.8%) showed degeneration and necrosis of renal tubular epithelial cells, four cases (18.2%) showed T cell-mediated acute rejection and six cases (27.3%) showed renal interstitial inflammation. There were two cases (9.1%) of renal dysplasia and one case (4.5%) of renal infarction. There was insufficient evidence for diagnosis of renal allograft nephropathy. Compared to post-transplant kidney from adult C-III donors, the proportion of drug toxicity damage was higher (P<0.05). Compared to post-transplant kidney from adult cadavers, the proportions of drug toxicity damage, degeneration and necrosis of renal tubular epithelial cells were higher (P<0.05) while the proportion of acute rejection was lower (P<0.05). CONCLUSIONS: The pathologic changes in the post-transplant kidneys from pediatric donors are different from those from adult donors. Optimal long-term outcome can be accomplished by effective treatment based on timely or procedural biopsy. PMID- 26879430 TI - [Diagnostic value of STAT6 immunohistochemistry in solitary fibrous tumor/meningeal hemangiopericytoma]. AB - OBJECTIVE: To investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC). METHOD: Evaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining. RESULTS: All SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6. CONCLUSIONS: STAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC. PMID- 26879431 TI - [Tuberous sclerosis complex with refractory epilepsy: a clinicopathologic study of 14 cases]. AB - OBJECTIVE: To study the clinicopathologic features of tuberous sclerosis complex (TSC). METHODS: The clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed. RESULTS: Fourteen cases were included, the mean age was (15.8+/-12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case. CONCLUSIONS: Diagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC. PMID- 26879432 TI - [Complete atrioventricular septal defect: a clinicopathologic study of 35 cases]. AB - OBJECTIVE: To investigate the autopsy characteristics, pathologic type, malfomation and genetic characteristics of complete atrioventricular septal defect (CAVSD). METHODS: Thirty five cases of CAVSD were collected from Maternal and Child Hospital of Haidian District during Jan.2003 to Jan.2015. Autoptic material, clinical history and chromosome examination were reviewed. RESULTS: Among 35 cases of CAVSD between 18-38 gestational weeks, there were 26 cases with CAVSD A (74.3%, 26/35), 1 case with CAVSD B (2.8%, 1/35) and 8 cases with CAVSD C (22.8%, 8/35). Only CAVSD malformation was seen in 4 cases (11.4%, 4/35). Multiple malformations were seen in 31 cases (88.6%, 31/35). Combined malformations most frequently occurred in cardiovascular, respiratory and locomotor system. Among 15 cases with chromosome examination, chromosome aberrations was found in 13 cases (13/15) and trisomy-21 was found in 11 cases (11/15). CONCLUSIONS: CAVSD is a rare disease and CAVSD A is the most common type. CAVSD is usually combined with other malformations and chromosome aberrations. PMID- 26879433 TI - [AML1 gene signal patterns and clinical significance in 337 patients with B-cell acute lymphoblastic leukemia]. PMID- 26879434 TI - [Clinicopathologic analysis of cerebellar hemangioblastoma]. PMID- 26879435 TI - [Ultrastructural characteristics of medulloblastoma]. PMID- 26879436 TI - [Comparison of droplet digital PCR and IHC combined FISH in detection of breast carcinoma HER2 amplification]. PMID- 26879437 TI - [Swelling of bilateral tonsils]. PMID- 26879438 TI - [Blastic plasmacytoid dendritic cell neoplasm presenting as myeloid leukemia: report of a case]. PMID- 26879439 TI - [Hepatoid adenocarcinoma of the gallbladder: report of a case]. PMID- 26879440 TI - [Primary perivascular epithelioid cell tumour of femoral: report of a case]. PMID- 26879441 TI - [Ectopic hamartomatous thymoma demonstrating skin adnexal differentiation: report of a case]. PMID- 26879442 TI - [Gastric cacinosarcoma: report of a case]. PMID- 26879443 TI - [Rosette-forming epithelioid osteosarcoma in childhood: report of a case]. PMID- 26879444 TI - [Advances in molecular dignostics and target therapy of lymphoma]. PMID- 26879445 TI - [Research progress and prospect of CRISPR/Cas9 system]. PMID- 26879447 TI - Determination of Electron Optical Properties for Aperture Zoom Lenses Using an Artificial Neural Network Method. AB - Multi-element electrostatic aperture lens systems are widely used to control electron or charged particle beams in many scientific instruments. By means of applied voltages, these lens systems can be operated for different purposes. In this context, numerous methods have been performed to calculate focal properties of these lenses. In this study, an artificial neural network (ANN) classification method is utilized to determine the focused/unfocused charged particle beam in the image point as a function of lens voltages for multi-element electrostatic aperture lenses. A data set for training and testing of ANN is taken from the SIMION 8.1 simulation program, which is a well known and proven accuracy program in charged particle optics. Mean squared error results of this study indicate that the ANN classification method provides notable performance characteristics for electrostatic aperture zoom lenses. PMID- 26879446 TI - High melphalan exposure is associated with improved overall survival in myeloma patients receiving high dose melphalan and autologous transplantation. AB - AIM: High dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim of this study was to determine whether HDM exposure (area under the concentration vs. time curve, AUC), is significantly associated with transplant outcomes. METHODS: Melphalan concentrations were measured in six to 11 plasma samples collected after HDM (median 192 mg m(-) (2) ) to determine melphalan AUC for a total of 114 patients. Binary logistic regression was used to assess whether melphalan AUC was associated with severe (>= grade 3) oral mucositis. Multivariate Cox regression was used to assess whether melphalan AUC was significantly associated with time to progression, progression-free survival and overall survival (OS). RESULTS: Melphalan AUC ranged from 4.9 to 24.6 mg l(-1) h, median 12.84 mg l(-1) h. Melphalan AUC above the median was a risk factor for severe mucositis (HR 1.21, 95% CI 1.06, 1.38, P = 0.004) but was also associated with significantly improved overall survival (OS) (HR 0.40, 95% CI 0.20, 0.81, P = 0.001), with an estimated median survival of 8.50 years vs. 5.38 years for high vs. low AUC groups. Multivariate analysis did not identify melphalan AUC as being significantly associated with time to progression or progression-free survival. CONCLUSIONS: This large scale pharmacodynamic analysis of HDM demonstrates that high melphalan exposure is associated with improved survival, with an acceptable increase in transplant toxicity. These results suggest studies targeting a higher AUC are warranted in patients undergoing HDM and ASCT for myeloma. PMID- 26879448 TI - Congenital disorder of glycosylphosphatidylinositol (GPI)-anchor biosynthesis- The phenotype of two patients with novel mutations in the PIGN and PGAP2 genes. AB - BACKGROUND: Glycosylphosphatidylinositol (GPI)-anchor deficiencies are a new subclass of congenital disorders of glycosylation. About 26 genes are involved in the GPI-anchor biosynthesis and remodeling pathway, of which mutations in thirteen have been reported to date as causative of a diverse spectrum of intellectual disabilities. Since the clinical phenotype of these disorders varies and the number of described individuals is limited, we present new patients with inherited GPI-anchor deficiency (IGD) caused by mutations in the PGAP2 and PIGN genes. PATIENTS AND METHODS: The first girl presented with profound psychomotor retardation, low birth parameters, and chest deformities already existing in neonatal period. The disease course was slowly progressive with severe hypotonia, chronic fever, and respiration insufficiency at the age of 6. The second girl showed profound psychomotor retardation, marked hypotonia, and high birth weight (97 centile). Dysmorphy was mild or absent in both girls. Whole exome sequencing revealed novel variants in the genes PGAP2 (c.2T>G and c.221G>A) and PIGN (c.790G>A and c.932T>G). Impaired GPI binding were was subsequently uncovered, although the hyperactivity of alkaline phosphatase (a GPI-anchored protein) occurred only in first case. CONCLUSIONS: Based on our results we can conclude that: 1. GPI-anchor biosynthesis disorders may represent a relatively frequent and overlooked metabolic defect; 2. The utility of GPI binding assessment as a screening test for this group of rare diseases requires further studies. PMID- 26879449 TI - The roles of the hybrid cluster protein, Hcp and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress. AB - The hybrid cluster protein, Hcp, contains a 4Fe-2S-2O iron-sulfur-oxygen cluster that is currently considered to be unique in biology. It protects various bacteria from nitrosative stress, but the mechanism is unknown. We demonstrate that the Escherichia coli Hcp is a high affinity nitric oxide (NO) reductase that is the major enzyme for reducing NO stoichiometrically to N2 O under physiologically relevant conditions. Deletion of hcp results in extreme sensitivity to NO during anaerobic growth and inactivation of the iron-sulfur proteins, aconitase and fumarase, by accumulated cytoplasmic NO. Site directed mutagenesis revealed an essential role in NO reduction for the conserved glutamate 492 that coordinates the hybrid cluster. The second gene of the hcp-hcr operon encodes an NADH-dependent reductase, Hcr. Tight interaction between Hcp and Hcr was demonstrated. Although Hcp and Hcr purified individually were inactive or when recombined, a co-purified preparation reduced NO in vitro with a Km for NO of 500 nM. In an hcr mutant, Hcp is reversibly inactivated by NO concentrations above 200 nM, indicating that Hcr protects Hcp from nitrosylation by its substrate, NO. PMID- 26879451 TI - Analysis of endogenous aldehydes in human urine by static headspace gas chromatography-mass spectrometry. AB - Endogenous aldehydes (EAs) generated during oxidative stress and cell processes are associated with many pathogenic and toxicogenic processes. The aim of this research was to develop a solvent-free and automated analytical method for the determination of EAs in human urine using a static headspace generator sampler coupled with gas chromatography-mass spectrometry (HS-GC-MS). Twelve significant EAs used as markers of different biochemical and physiological processes, namely short- and medium-chain alkanals, alpha,beta-unsaturated aldehydes and dicarbonyl aldehydes have been selected as target analytes. Human urine samples (no dilution is required) were derivatized with O-2,3,4,5,6-pentafluorobenzylhydroxylamine in alkaline medium (hydrogen carbonate-carbonate buffer, pH 10.3). The HS-GC-MS method developed renders an efficient tool for the sensitive and precise determination of EAs in human urine with limits of detection from 1 to 15ng/L and relative standard deviations, (RSDs) from 6.0 to 7.9%. Average recoveries by enriching urine samples ranged between 92 and 95%. Aldehydes were readily determined at 0.005-50MUg/L levels in human urine from healthy subjects, smokers and diabetic adults. PMID- 26879450 TI - Social Network and Mental Health Among Older Adults in Rural Uttar Pradesh, India: A Cross-Sectional Study. AB - The rapid growth of the older population in India draws attention to the factors that contribute to their changing health realities. However, there has hardly been any study in India that has looked at the effects of specific social networks with children, relatives, friends and confidant on depression among older adults. The objective of the study is to investigate the association between social network and depression among the rural elderly. The study population comprised over 630 older adults (aged 60 and above) from the rural areas of Varanasi, Uttar Pradesh. We adopted Berkman's theoretical model of the impact of social relations on depression among the elderly in the Indian context. Results of the Confirmatory Factor Analysis (CFA) demonstrated that the four specific social network types: children, relatives, friends and confidant were tenable. The results showed that a better social network with 'friends/neighbours' was protective against depression among the rural elderly. This clearly points to the need for more social network centres for older adults, so that they can interact with friends within the community or between communities and participate in group activities. PMID- 26879452 TI - Stable isotope dilution ultra-high performance liquid chromatography-tandem mass spectrometry quantitative profiling of tryptophan-related neuroactive substances in human serum and cerebrospinal fluid. AB - Many compounds related to L-tryptophan (L-TRP) have interesting biological or pharmacological activity, and their abnormal neurotransmission seems to be linked to a wide range of neurodegenerative and psychiatric diseases. A high-throughput method based on ultra-high performance liquid chromatography connected to electrospray tandem mass spectrometry (UHPLC-ESI-MS/MS) was developed for the quantitative analysis of L-TRP and 16 of its metabolites in human serum and cerebrospinal fluid (CSF), representing both major and minor routes of L-TRP catabolism. The combination of a fast LC gradient with selective tandem mass spectrometry enabled accurate analysis of almost 100 samples in 24h. The standard isotope dilution method was used for quantitative determination. The method's lower limits of quantification for serum and cerebrospinal fluid ranged from 0.05 to 15nmol/L and 0.3 to 45nmol/L, respectively. Analytical recoveries ranged from 10.4 to 218.1% for serum and 22.1 to 370.0% for CSF. The method's accuracy ranged from 82.4 to 128.5% for serum matrix and 90.7 to 127.7% for CSF matrix. All intra and inter-day coefficients of variation were below 15%. These results demonstrate that the new method is capable of quantifying endogenous serum and CSF levels of a heterogeneous group of compounds spanning a wide range of concentrations. The method was used to determine the physiological levels of target analytes in serum and CSF samples from 18 individuals, demonstrating its reliability and potential usefulness in large-scale epidemiological studies. PMID- 26879453 TI - Application of a quantitative structure retention relationship approach for the prediction of the two-dimensional gas chromatography retention times of polycyclic aromatic sulfur heterocycle compounds. AB - Information on the sulfur classes present in petroleum is a key factor in determining the value of refined products and processing behavior in the refinery. A large part of the sulfur present is included in polycyclic aromatic sulfur heterocycles (PASHs), which in turn are difficult to desulfurize. Furthermore, some PASHs are potentially more mutagenic and carcinogenic than polycyclic aromatic hydrocarbons, PAHs. All of this calls for improved methods for the identification and quantification of individual sulfur species. Recent advances in analytical techniques such as comprehensive two-dimensional gas chromatography (GC*GC) have enabled the identification of many individual sulfur species. However, full identification of individual components, particularly in virgin oil fractions, is still out of reach as standards for numerous compounds are unavailable. In this work, a method for accurately predicting retention times in GC*GC using a QSRR (quantitative structure retention relationship) method was very helpful for the identification of individual sulfur compounds. Retention times for 89 saturated, aromatic, and polyaromatic sulfur-containing heterocyclic compounds were determined using two-dimensional gas chromatography. These retention data were correlated with molecular descriptors generated with CODESSA software. Two independent QSRR relationships were derived for the primary as well as the secondary retention characteristics. The predictive ability of the relationships was tested by using both independent sets of compounds and a cross validation technique. When the corresponding chemical standards are unavailable, the equations developed for predicting retention times can be used to identify unknown chromatographic peaks by matching their retention times with those of sulfur compounds of known molecular structure. PMID- 26879454 TI - Retentivity, selectivity and thermodynamic behavior of polycyclic aromatic hydrocarbons on charge-transfer and hypercrosslinked stationary phases under conditions of normal phase high performance liquid chromatography. AB - Charge-transfer and hypercrosslinked polystyrene phases offer retention and separation for polycyclic aromatic hydrocarbons (PAHs) and thus have potential for petroleum analysis. The size, shape and planarity selectivity for PAH standards on charge-transfer (DNAP column) and hypercrosslinked polystyrene (HC Tol and 5HGN columns) phases are different under normal phase liquid chromatography (NPLC). The HC-Tol column behaves like a conventional NPLC column with low retention of PAHs. Retention of PAHs on the DNAP and 5HGN are strong and increases with the number of aromatic rings. The main retention mechanism is through pi-pi interactions and dipole-induced dipole interaction. Thermodynamics indicates that the retention mechanism of PAHs remains unchanged over the temperature range 20-60 degrees C. In addition, on either DNAP or 5HGN column, both linear and bent PAHs are retained through the same mechanism. But DNAP possesses smaller pi-pi interaction and higher planarity selectivity than 5HGN for PAHs. This is suggestive that DNAP interacts with PAHs through a disordered phase arrangement, while 5HGN behaves as an ordered adsorption phase. PMID- 26879455 TI - Development of a modified acetonitrile-based extraction procedure followed by ultra-high performance liquid chromatography-tandem mass spectrometry for the analysis of psychiatric drugs in sediments. AB - An analytical method based on a modified Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) extraction procedure followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was developed for the analysis of psychiatric drugs in sediments. An optimized approach was applied in sample preparation by using basic acetonitrile as extraction solvent. Extraction was followed by a clean-up using dispersive solid phase extraction (dSPE) to remove matrix interfering compounds. The analytical method was validated in terms of sensitivity, linearity, recovery, intra- and inter-day precisions and method detection and quantification limits. Under optimized conditions, limits of detection ranged from 0.01ngg(-1) to 2.08ngg(-1); and recoveries between 47 and 110% with relative standard deviation (RSD) below 5%. The developed methodology was applied to sediments of two Portuguese rivers (Douro and Lima rivers) and nine out of eleven psychiatric drugs were detected in sediments at concentrations up to 26.4ngg(-1) (dry weight). To the best of our knowledge, it was the first time that the human metabolites norfluoxetine and norsertraline were detected in river sediments at levels of few nanograms per gram. PMID- 26879456 TI - Microfluidic chip for stacking, separation and extraction of multiple DNA fragments. AB - A disposable integrated microfluidic device was developed for rapid sample stacking, separation and extraction of multiple DNA fragments from a relatively large amount of sample. Isotachophoresis hyphenated gel electrophoresis (ITP-GE) was used to pre-concentrate and separate DNA fragments, followed by extraction of pure DNA fragments with electroelution on-chip. DNA fragments of 200bp, 500bp and 1kbp were successfully separated and collected in the extraction chamber within 25min. The extraction efficiency obtained from the chip was 49.9%, 52.1% and 53.7% for 200bp, 500bp and 1kbp DNA fragments, respectively. The extracted DNA fragments exhibited compatibility with downstream enzymatic reactions, for example PCR. The chip was also used to extract DNA fragments with specific size range from sheared genomic DNA and demonstrated similar performance to that using traditional gel cutting method. The whole assay can finish in 32min, 6 times faster than traditional method. PMID- 26879457 TI - Application of spectral deconvolution and inverse mechanistic modelling as a tool for root cause investigation in protein chromatography. AB - In chromatographic protein purification, process variations, aging of columns, or processing errors can lead to deviations of the expected elution behavior of product and contaminants and can result in a decreased pool purity or yield. A different elution behavior of all or several involved species leads to a deviating chromatogram. The causes for deviations are however hard to identify by visual inspection and complicate the correction of a problem in the next cycle or batch. To overcome this issue, a tool for root cause investigation in protein chromatography was developed. The tool combines a spectral deconvolution with inverse mechanistic modelling. Mid-UV spectral data and Partial Least Squares Regression were first applied to deconvolute peaks to obtain the individual elution profiles of co-eluting proteins. The individual elution profiles were subsequently used to identify errors in process parameters by curve fitting to a mechanistic chromatography model. The functionality of the tool for root cause investigation was successfully demonstrated in a model protein study with lysozyme, cytochrome c, and ribonuclease A. Deviating chromatograms were generated by deliberately caused errors in the process parameters flow rate and sodium-ion concentration in loading and elution buffer according to a design of experiments. The actual values of the three process parameters and, thus, the causes of the deviations were estimated with errors of less than 4.4%. Consequently, the established tool for root cause investigation is a valuable approach to rapidly identify process variations, aging of columns, or processing errors. This might help to minimize batch rejections or contribute to an increased productivity. PMID- 26879458 TI - The Cost Effectiveness of Nalmefene for Reduction of Alcohol Consumption in Alcohol-Dependent Patients with High or Very High Drinking-Risk Levels from a UK Societal Perspective. AB - AIM: To evaluate costs and health outcomes of nalmefene plus psychosocial support, compared with psychosocial intervention alone, for reducing alcohol consumption in alcohol-dependent patients, specifically focusing on societal costs related to productivity losses and crime. METHODS: A Markov model was constructed to model costs and health outcomes of the treatments over 5 years. Analyses were conducted for nalmefene's licensed population: adults with both alcohol dependence and high or very high drinking-risk levels (DRLs) who do not require immediate detoxification and who have high or very high DRLs after initial assessment. The main outcome measure was cost per quality-adjusted life year (QALY) gained as assessed from a UK societal perspective. Alcohol attributable productivity loss, crime and health events occurring at different levels of alcohol consumption were taken from published risk-relation studies. Health-related and societal costs were drawn from public data and the literature. Data on the treatment effect, as well as baseline characteristics of the modelled population and utilities, came from three pivotal phase 3 trials of nalmefene. RESULTS: Nalmefene plus psychosocial support was dominant compared with psychosocial intervention alone, resulting in QALYs gained and reduced societal costs. Sensitivity analyses showed that this conclusion was robust. Nalmefene plus psychosocial support led to per-patient reduced costs of L3324 and L2483, due to reduced productivity losses and crime events, respectively. CONCLUSION: Nalmefene is cost effective from a UK societal perspective, resulting in greater QALY gains and lower costs compared with psychosocial support alone. Nalmefene demonstrates considerable public benefits by reducing alcohol-attributable productivity losses and crime events in adults with both alcohol dependence and high or very high DRLs who do not require immediate detoxification and who have high or very high DRLs after initial assessment. PMID- 26879460 TI - Meaning of Illness and Cardiovascular Risk Factors in Patients With Type 2 Diabetes. AB - PURPOSE: The purpose of this study was to examine the relationship between meaning of illness and cardiovascular disease risk factors in patients with type 2 diabetes. METHODS: The sample population was recruited from primary care clinics in the southeastern United States. The meaning of illness was assessed by a validated questionnaire with 5 subscales. The primary outcomes were cardiovascular disease (CVD) risk factors, assessed by A1C, systolic and diastolic blood pressure (SBP and DBP, respectively), and low-density lipoprotein cholesterol (LDL-C). Multivariate linear regression models investigated associations between the clinical outcomes and the 5 MIQ factors, controlling for possible confounders. RESULTS: The sample comprised 302 black and white participants of whom more than half were elderly (65+ years) and the vast majority were male (98%). Systolic blood pressure was positively associated with non-anticipated vulnerability. Diastolic blood pressure was negatively associated with degree of stress/change in commitments and positively associated with challenge/motivation/hope and non-anticipated vulnerability. Low-density lipoprotein cholesterol was significantly and negatively associated with degree of stress/change in commitments. CONCLUSIONS: Meaning of illness had a significant effect on measured outcomes of CVD risk. The specific factor included in the overarching concept of meaning of illness differed in its influence, with more positive views of stress/commitments associated with lower blood pressure and LDL but more positive views of the challenge/hope/motivation and negative views of non-anticipated vulnerability associated with diabetes associated with higher systolic and diastolic blood pressure. PMID- 26879459 TI - Effectiveness of Program Modification Strategies of the Diabetes Prevention Program: A Systematic Review. AB - PURPOSE: The purpose of this study is to review the effectiveness of commonly used program modifications classified under cultural adaptation and program translational strategies for the Diabetes Prevention Program (DPP) in terms of risk reduction for type 2 diabetes. METHODS: Authors extracted data about weight, body mass index (BMI), and 5 areas of program modification strategies from 28 interventions and analyzed them in SPSS software. Bivariate analyses examined the odds of achieving a significant reduction in outcomes by each modification of the DPP and by presence of a maintenance component, as well as the mean reduction of weight and BMI by more versus fewer modifications and by the presence of a maintenance component. RESULTS: There were no statistically significant differences in achieving a significant reduction in weight or BMI by any type of modification or by the presence of a maintenance component. Programs with fewer modifications reported significantly greater reduction in mean weight at 12 months postintervention and the furthest time point extracted. Programs with a maintenance component achieved significantly greater reduction in mean weight measured at the furthest time point extracted. CONCLUSIONS: The DPP appears to be programmatically robust to a variety of cultural adaptation and translational strategies. Potentially cost-saving modifications do not seem to reduce effectiveness, which should encourage implementation on a broader scale. Program planners should, however, make efforts to include maintenance components because they appear to significantly reduce risk for acquiring type 2 diabetes. PMID- 26879461 TI - Patterned growth of luminescent metal-organic framework films: a versatile electrochemically-assisted microwave deposition method. AB - Electrochemically-assisted microwave deposition technology, a facile method for the fabrication of luminescent metal-organic framework (LMOF) films, is presented herein. This method was further developed into a versatile method for preparing patterned LMOF films. The strategy based on this method can spatially locate microcrystals of MOFs on a surface, which provides great promise in anti counterfeiting barcode applications. PMID- 26879462 TI - How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study. AB - A recent research article by the National Center for Computational Toxicology (NCCT) (Kleinstreuer et al., 2013), indicated that high throughput screening (HTS) data from assays linked to hallmarks and presumed pathways of carcinogenesis could be used to predict classification of pesticides as either (a) possible, probable or likely rodent carcinogens; or (b) not likely carcinogens or evidence of non-carcinogenicity. Using independently developed software to validate the computational results, we replicated the majority of the results reported. We also found that the prediction model correlating cancer pathway bioactivity scores with in vivo carcinogenic effects in rodents was not robust. A change of classification of a single chemical in the test set was capable of changing the overall study conclusion about the statistical significance of the correlation. Furthermore, in the subset of pesticide compounds used in model validation, the accuracy of prediction was no better than chance for about three quarters of the chemicals (those with fewer than 7 positive outcomes in HTS assays representing the 11 histopathological endpoints used in model development), suggesting that the prediction model was not adequate to predict cancer hazard for most of these chemicals. Although the utility of the model for humans is also unclear because a number of the rodent responses modeled (e.g., mouse liver tumors, rat thyroid tumors, rat testicular tumors, etc.) are not considered biologically relevant to human responses, the data examined imply the need for further research with HTS assays and improved models, which might help to predict classifications of in vivo carcinogenic responses in rodents for the pesticide considered, and thus reduce the need for testing in laboratory animals. PMID- 26879464 TI - Thermal biology of the sub-polar-temperate estuarine crab Hemigrapsus crenulatus (Crustacea: Decapoda: Varunidae). AB - Optimum temperatures can be measured through aerobic scope, preferred temperatures or growth. A complete thermal window, including optimum, transition (Pejus) and critical temperatures (CT), can be described if preferred temperatures and CT are defined. The crustacean Hemigrapsus crenulatus was used as a model species to evaluate the effect of acclimation temperature on: (i) thermal preference and width of thermal window, (ii) respiratory metabolism, and (iii) haemolymph proteins. Dependant on acclimation temperature, preferred temperature was between 11.8 degrees C and 25.2 degrees C while CT was found between a minimum of 2.7 degrees C (CTmin) and a maximum of 35.9 degrees C (CTmax). These data and data from tropical and temperate crustaceans were compared to examine the association between environmental temperature and thermal tolerance. Temperate species have a CTmax limit around 35 degrees C that corresponded with the low CTmax limit of tropical species (34-36 degrees C). Tropical species showed a CTmin limit around 9 degrees C similar to the maximum CTmin of temperate species (5-6 degrees C). The maximum CTmin of deep sea species that occur in cold environments (2.5 degrees C) matched the low CTmin values (3.2 degrees C) of temperate species. Results also indicate that the energy required to activate the enzyme complex (Ei) involved in respiratory metabolism of ectotherms changes along the latitudinal gradient of temperature. PMID- 26879463 TI - Extending (Q)SARs to incorporate proprietary knowledge for regulatory purposes: A case study using aromatic amine mutagenicity. AB - Statistical-based and expert rule-based models built using public domain mutagenicity knowledge and data are routinely used for computational (Q)SAR assessments of pharmaceutical impurities in line with the approach recommended in the ICH M7 guideline. Knowledge from proprietary corporate mutagenicity databases could be used to increase the predictive performance for selected chemical classes as well as expand the applicability domain of these (Q)SAR models. This paper outlines a mechanism for sharing knowledge without the release of proprietary data. Primary aromatic amine mutagenicity was selected as a case study because this chemical class is often encountered in pharmaceutical impurity analysis and mutagenicity of aromatic amines is currently difficult to predict. As part of this analysis, a series of aromatic amine substructures were defined and the number of mutagenic and non-mutagenic examples for each chemical substructure calculated across a series of public and proprietary mutagenicity databases. This information was pooled across all sources to identify structural classes that activate or deactivate aromatic amine mutagenicity. This structure activity knowledge, in combination with newly released primary aromatic amine data, was incorporated into Leadscope's expert rule-based and statistical-based (Q)SAR models where increased predictive performance was demonstrated. PMID- 26879465 TI - Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation. AB - The proliferation of intestinal stem cells (ISCs) and differentiation of enteroblasts to form mature enteroendocrine cells and enterocytes in the Drosophila intestinal epithelium must be tightly regulated to maintain homeostasis. We show that genetic modulation of CyclinD/Cdk4 activity or mTOR dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC proliferation and enteroblast differentiation. Increased enterocyte growth results in higher numbers of ISCs and defective enterocyte growth reduces ISC abundance and proliferation in the midgut. Adult midguts deficient for Cdk4 show severe disruption of intestinal homeostasis characterised by decreased ISC self-renewal, enteroblast differentiation defects and low enteroendocrine cell and enterocyte numbers. The ISC/enteroblast phenotypes result from a combination of cell autonomous and non-autonomous requirements for Cdk4 function. One non-autonomous consequence of Cdk4-dependent deficient enterocyte growth is high expression of Delta in ISCs and Delta retention in enteroblasts. We postulate that aberrant activation of the Delta-Notch pathway is a possible partial cause of lost ISC stemness. These results support the idea that enterocytes contribute to a putative stem cell niche that maintains intestinal homeostasis in the Drosophila anterior midgut. PMID- 26879466 TI - Engrailed 1 shapes the dopaminergic and serotonergic landscape through proper isthmic organizer maintenance and function. AB - The isthmic organizer (IsO) is a signaling center that specifies the correct and distinct embryonic development of the dopaminergic midbrain and serotonergic hindbrain. The IsO is a linear boundary between the two brain regions, emerging at around embryonic day 7-8 of murine embryonic development, that shapes its surroundings through the expression of instructive signals such as Wnt and growth factors. Homeobox transcription factor engrailed 1 (En1) is present in midbrain and rostral hindbrain (i.e. rhombomere 1, R1). Its expression spans the IsO, and it is known to be an important survival factor for both dopaminergic and serotonergic neurons. Erroneous composition of dopaminergic neurons in the midbrain or serotonergic neurons in the hindbrain is associated with severe pathologies such as Parkinson's disease, depression or autism. Here we investigated the role of En1 in early mid-hindbrain development, using multiple En1-ablated mouse models as well as lineage-tracing techniques, and observed the appearance of ectopic dopaminergic neurons, indistinguishable from midbrain dopaminergic neurons based on molecular profile and intrinsic electrophysiological properties. We propose that this change is the direct result of a caudal relocation of the IsO as represented by ectopic presence of Fgf8, Otx2, Wnt1 and canonical Wnt-signalling. Our work suggests a newly-discovered role for En1: the repression of Otx2, Wnt1 and canonical Wnt-signaling in R1. Overall, our results suggest that En1 is essential for proper IsO maintenance and function. PMID- 26879468 TI - Low temperature adaptation and the effects of cryoprotectants on mesorhizobia strains. AB - In this study, the tolerance of Mesorhizobium sp. ACMP18, Mesorhizobium sp. USDA3350, and Mesorhizobium temperatum LMG23931 strains, to cold and freezing were investigated. The ability to withstand freezing at -20 degrees C and -70 degrees C for 24 months was different among the studied strains and depended on the cryoprotectant used. The survivability of mesorhizobial strains at -20 degrees C and -70 degrees C was significantly improved by some cryoprotectans (glycerol and sucrose/peptone). It is worth noting that the greatest resistance to freezing was detected when stress treatments were performed in glycerol as a cryoprotectant. Using PCR analysis, cspA genes were identified in the studied strains. Their nucleotide sequences were most similar to the sequences of the corresponding genes of the Mesorhizobium species. The expression of the cspA gene in the studied bacteria was analyzed using the RT-PCR technique. The fatty acid composition of the mesorhizobia was determined at 5, 10, 15, and 28 degrees C. It was noticed that growth temperature significantly affected the fatty acid composition and the amounts of unsaturated fatty acids, especially that of cis vaccenic acid (18:1omega(11)), increased markedly in bacterial cells cultivated at 5, 10, and 15 degrees C. PMID- 26879469 TI - Computational Study of Formic Acid Dehydrogenation Catalyzed by Al(III) Bis(imino)pyridine. AB - The mechanism of formic acid dehydrogenation catalyzed by the bis(imino)pyridine ligated aluminum hydride complex (PDI(2-))Al(THF)H (PDI=bis(imino)pyridine) was studied by density functional theory calculations. The overall transformation is composed of two stages: catalyst activation and the catalytic cycle. The catalyst activation begins with O-H bond cleavage of HCOOH promoted by aluminum-ligand cooperation, followed by HCOOH-assisted Al-H bond cleavage, and protonation of the imine carbon atom of the bis(imino)pyridine ligand. The resultant doubly protonated complex ((H,H) PDI)Al(OOCH)3 is the active catalyst for formic acid dehydrogenation. Given this, the catalytic cycle includes beta-hydride elimination of ((H,H) PDI)Al(OOCH)3 to produce CO2, and the formed ((H,H) PDI)Al(OOCH)2 H mediates HCOOH to release H2. PMID- 26879467 TI - Outcomes of chronic frontal sinusitis treated with ethmoidectomy: a prospective study. AB - BACKGROUND: In medically refractory chronic frontal sinusitis, ethmoidectomy without instrumentation of the frontal ostium may resolve frontal disease. Our aim was to determine the efficacy of ethmoidectomy alone for the treatment of chronic frontal sinusitis. METHODS: Adults with chronic rhinosinusitis prospectively enrolled in a multicenter study who demonstrated frontal sinusitis on computed tomography were divided into 2 groups: (1) endoscopic sinus surgery (ESS) incorporating ethmoidectomy, but excluding frontal sinusotomy; and (2) ESS incorporating frontal sinusotomy. The primary outcome was improvement in 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Secondary outcomes included endoscopic scores and use of corticosteroids and antibiotics. RESULTS: A total of 196 cases undergoing frontal sinusotomy and 30 cases treated with ethmoidectomy without frontal sinusotomy were analyzed and were comparable demographically. The prevalence of nasal polyps, previous ESS, asthma, and aspirin intolerance was more common in the frontal sinusotomy group (p < 0.050). Preoperative endoscopy and computed tomography scores were higher in the frontal sinusotomy group (p <= 0.001). Postoperatively, both groups showed comparable SNOT-22 scores with worse endoscopy scores in the frontal sinusotomy group (p = 0.038). Postoperative improvement in SNOT-22 total and subdomain scores was comparable between groups. Nasal endoscopy scores improved to a greater degree in the frontal sinusotomy group (p = 0.023). Duration of postoperative topical steroid use was higher in the frontal sinusotomy group (p = 0.007). Revision surgery was needed in 2.6% of frontal sinusotomy patients and 0% of patients without frontal sinusotomy. CONCLUSION: The treatment of chronic frontal sinusitis through ethmoidectomy is a potential alternative to frontal sinusotomy achieving similar quality of life (QOL) improvements in patients manifesting less severe sinus disease. PMID- 26879470 TI - Mechanism and rate constants of the Cdc42 GTPase binding with intrinsically disordered effectors. AB - Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder-to-order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock-and-coalesce, whereby one segment of the IDP first docks to its subsite on the target surface and the remaining segments subsequently coalesce around their respective subsites. Here we applied our TransComp method within the framework of the dock-and-coalesce mechanism to dissect the binding kinetics of two Rho-family GTPases, Cdc42 and TC10, with two intrinsically disordered effectors, WASP and Pak1. TransComp calculations identified the basic regions preceding the GTPase binding domains (GBDs) of the effectors as the docking segment. For Cdc42 binding with both WASP and Pak1, the calculated docking rate constants are close to the observed overall binding rate constants, suggesting that basic-region docking is the rate-limiting step and subsequent conformational coalescence of the GBDs on the Cdc42 surface is fast. The possibility that conformational coalescence of the WASP GBD on the TC10 surface is slow warrants further experimental investigation. The account for the differences in binding rate constants among the three GTPase-effector systems and mutational effects therein yields deep physical and mechanistic insight into the binding processes. Our approach may guide the selection of mutations that lead to redesigned binding pathways. PMID- 26879472 TI - When can we be sure an intervention is cost-effective? PMID- 26879471 TI - Tuning Charge Transfer in Ion-Surface Collisions at Hyperthermal Energies. AB - Charge exchange in ion-surface collisions may be influenced by surface adsorbates to alter the charge state of the scattered projectiles. We show here that the positive-ion yield, observed during ion scattering on metal surfaces at low incident energies, is greatly enhanced by adsorbing electronegative species onto the surface. Specifically, when beams of N(+) and O(+) ions are scattered off of clean Au surfaces at hyperthermal energies, no positive ions are observed exiting. Partial adsorption of F atoms on the Au surface, however, leads to the appearance of positively charged primary ions scattering off of Au, a direct result of the increase in the Au work function. The inelastic energy losses for positive-ion exits are slightly larger than the corresponding ionization energies of the respective N and O atoms, which suggest that the detected positive ions are formed by surface reionization during the hard collision event. PMID- 26879473 TI - Highly Unsaturated Platinum and Palladium Carbenes PtC3 and PdC3 Isolated and Characterized in the Gas Phase. AB - Carbenes of platinum and palladium, PtC3 and PdC3 , were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and ab initio calculations confirm that both molecules are linear. The geometry of PtC3 was accurately determined by fitting to the experimental moments of inertia of twenty-six isotopologues. The results are consistent with the proposal of an autogenic isolobal relationship between O, Au(+) , and Pt atoms. PMID- 26879474 TI - Prospective evaluation of Peristeen(r) transanal irrigation system with the validated neurogenic bowel dysfunction score sheet in the pediatric population. AB - AIMS: To determine the ability of Peristeen(r) transanal irrigation system to reduce symptoms of neurogenic bowel dysfunction (NBD) in patients using the validated neurogenic bowel dysfunction scoring system for the pediatric population. METHODS: Patients 3-21 years with NBD whose current bowel program was unsuccessful were given the Neurogenic Bowel Dysfunction (NBoDS) score sheet before initiating Peristeen(r), and at 2 weeks, 2 months, and 6 months after. All patients were started on Peristeen(r) with tap water (20 ml/kg) per daily irrigation. Mean and paired t-tests were completed. RESULTS: 24 patients were enrolled and had follow-up. Mean age was 10.5 years (range 3-21 years), 25%, 50%, 25% had thoracic, lumbar and sacral level lesions respectively. Mean NBoDS score at initiation of Peristeen(r) was 20.21 (+/-5.56), n = 24. The mean score after two weeks of use was 12.75 (+/-4.40), n = 24. There was a statistically significant decrease of 7.46 (95%CI, 5.07-9.84) points, t(23) = 6.47, P < 0.0005 after two weeks. There was a statistically significant decrease in their scores from initiation to the 2 month time period of 7.00 (95%CI, 2.18-11.82) points, t(9) = 3.29, P = 0.009. By the sixth month of daily use the mean NBoDS score was 9.67 (n = 12). This was an average decrease of 8.83 (95%CI, 5.39-12.28) points from initiation score, t(11) = 5.641, P < 0.005. CONCLUSION: The Peristeen(r) transanal irrigation system provides a significant reduction in NBoDS scores in pediatric patients with NBD. Peristeen(r) should be considered when other conservative bowel management options have been unsuccessful. Neurourol. Urodynam. 36:632-635, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26879475 TI - Update and recent advances on the management of invasive and chronic pulmonary aspergillosis. PMID- 26879476 TI - Invasive pulmonary Aspergillosis in organ transplants--Focus on lung transplants. AB - Infections with filamentous fungi are common in transplant recipients. The risk for aspergillosis and other invasive pulmonary mycosis (IPM) is high in patients undergoing stem cell and lung transplantations. The mortality rates range from 20% to 60% and depend on a number of risk factors. The typical manifestations of IPM are lung infiltrates, consolidations, and fungal tracheobronchitis. The most common infectious agent is Aspergillus fumigatus. Infections caused by non Aspergillus molds are more frequent for various reasons. The species distribution of non-Aspergillus molds varies in different locations. Furthermore, infections caused by Mucor and Penicillium are increasing, as are infections caused by species resistant to azoles and amphotericin B. Most centers use antifungal prophylaxis with inhaled amphotericin B or oral azoles. Early diagnosis and therapy is crucial. Reliable information on the local microbiological spectrum is a prerequisite for the effective treatment of molds with primary or secondary resistance to antimycotic drugs. PMID- 26879477 TI - Recent advances in chronic pulmonary aspergillosis. AB - Chronic pulmonary aspergillosis (CPA) is a slowly progressing pulmonary syndrome caused by Aspergillus spp. Specific knowledge regarding the disease entity, diagnosis method, and management is needed. This review focuses on the recent advances in our understanding of CPA. A new clinical disease entity of chronic progressive pulmonary aspergillosis consisting of chronic necrotizing pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis is proposed. Although newer antifungals are not available, evidence describing the treatment of CPA is accumulating. Longer administration of azoles is required for a better prognosis, but there is a risk of inducing azole resistance. Therapeutic drug monitoring and patient education are required. Establishing a drug-susceptibility test that can be performed in the general laboratory and the referral center are also important. Although the number of publications regarding CPA is growing, there are still many unanswered questions. Additional evidence and translational research regarding diagnosis, management, and drug resistance are urgently needed to improve the outcome of CPA. PMID- 26879478 TI - Clinical characteristics of patients with Aspergillus species isolation from respiratory samples: Comparison of chronic pulmonary aspergillosis and colonization. AB - BACKGROUND: With advancements in anti-fungal drugs, it has become more important to correctly diagnose chronic pulmonary aspergillosis (CPA); however, it is not easy to distinguish CPA from colonization when Aspergillus species are isolated from respiratory samples. The aim of the study was to clarify the particular clinical characteristics of patients with CPA vs. those with colonization. METHODS: We retrospectively reviewed the medical records of 110 patients with Aspergillus species isolation from respiratory samples, to analyze and compare the differences between CPA and colonization of the Aspergillus species. RESULTS: The median age of all analyzed was 71 years (range: 31-92 years); 64 were female (58%). The most frequently cultured Aspergillus species was Aspergillus fumigatus (48.3%), followed by A. niger (29.2%). Thirty patients (27.4%) were diagnosed with CPA, vs. 75 (68.2%) with colonization and 5 (4.5%) with allergic bronchopulmonary aspergillosis. Compared with the colonization group, the CPA group included more males (CPA vs. colonization: 49.3% vs. 13.3%) and subjects with a low body mass index (18.45 kg/m2 vs. 21.09 kg/m2). As for the underlying pulmonary diseases, the patients with CPA showed a significantly higher prevalence of sequelae of pulmonary tuberculosis (40% vs. 8%) and a history of thoracic surgery (43% vs. 13%) than those with colonization. Asthma was less frequent in the CPA group than in the colonization group (0% vs. 20%). We found no significantly important underlying extrapulmonary diseases. CONCLUSIONS: Patients with CPA display clinical characteristics distinct from those seen in subjects with colonization. PMID- 26879479 TI - Receptor for advanced glycation end products expressed on alveolar epithelial cells is the main target for hyperoxia-induced lung injury. AB - BACKGROUND: Receptor for advanced glycation end products (RAGE) is abundantly expressed on alveolar epithelial cells (AECs) and participates in innate immune responses such as apoptosis and inflammation. However, it is unclear whether RAGE mediated apoptosis of AECs is associated with hyperoxia-induced lung injury. METHODS: We used wild-type and RAGE-knockout C57BL6/J mice in this study. In addition, we developed bone marrow chimeric mouse models expressing RAGE on hematopoietic or non-hematopoietic cells, including lung parenchymal cells, and compared survival ratios and changes in the permeability of the alveolar capillary barrier after hyperoxia exposure. Further, we prepared single cell suspensions of lung cells and evaluated the apoptosis of AECs or microvascular endothelial cells (MVECs) by using a combination of antibodies and JC-1 dye. We also examined whether RAGE inhibition decreased hyperoxia-induced apoptosis of human lung epithelial cells in vitro. RESULTS: After hyperoxia exposure, mice expressing RAGE on lung cells showed lower survival rate and increased alveolar capillary permeability than mice expressing RAGE on hematopoietic cells. RAGE expressing AECs showed significantly higher apoptosis than RAGE-knockout AECs after in vivo hyperoxia exposure. The level of hyperoxia-induced apoptosis was not different in MVECs. However, RAGE-null lung epithelial cells showed lower apoptosis than RAGE-expressing cells in vitro. CONCLUSION: These results indicated that RAGE on AECs mainly contributed to hyperoxia-induced lung injury and alveolar-capillary barrier disruption. PMID- 26879480 TI - Cholesteryl palmitate crystals in bronchoalveolar lavage fluid smears as a possible prognostic biomarker for chronic interstitial pneumonia: A preliminary study. AB - BACKGROUND: We observed cholesterol-like crystals (Crystal X) in the bronchoalveolar lavage fluid (BALF) smears of patients with diffuse pulmonary disease. We analyzed the clinical data of patients with and without crystals, and elucidated the structure of Crystal X and its concentration in the BALF. METHODS: Two hundred eighty-nine patients with diffuse pulmonary disease who underwent bronchoalveolar lavage (BAL) were analyzed. The relationships between the presence and number of Crystal X in BALF smears and clinical parameters were investigated. Furthermore, structure determination and quantitative analyses of the crystals were performed. RESULTS: Seventy-five (26.0%) patients had Crystal X in their BALF. The crystals were frequently observed in patients with chronic interstitial pneumonia (CIP, 60/160=35.3%). Patients with Crystal X exhibited significantly higher serum Kerbs von Lungren 6 antigen and surfactant protein-D levels (P<0.01) and lower percentage vital capacity (P<0.05) than patients without Crystal X. The number of crystals was significantly correlated with these parameters. The presence of crystals was also associated with a lower survival rate at 1 year after the BAL. The interfacial angles of the crystals were 126+/-2 degrees and 144+/-2 degrees , different from those of cholesterol monohydrate crystals. Infrared absorption spectrometry showed Crystal X was cholesteryl palmitate. Its concentration was significantly higher in BALF with crystals than in BALF without crystals (P<0.01). CONCLUSIONS: Crystal X in the BALF of patients with diffuse pulmonary disease was identified as cholesteryl palmitate, which may be a useful prognostic biomarker for CIP. PMID- 26879482 TI - Bronchial occlusion with Endobronchial Watanabe Spigots for massive hemoptysis in a patient with pulmonary Mycobacterium avium complex infection. AB - The safety of occlusion with Endobronchial Watanabe Spigots (EWS) for the management of hemoptysis associated with chronic respiratory tract infection has not yet been established. A 57-year-old woman diagnosed as having pulmonary Mycobacterium avium complex (MAC) infection presented to our hospital with hemoptysis. She underwent bronchoscopy for bronchial occlusion with EWS, which resulted in the resolution of hemoptysis. Subsequently, she underwent bronchial artery embolization and then EWS were removed. During placement of EWS, no worsening of infection was observed. After removal of EWS, there was no recurrence of hemoptysis. Bronchial occlusion with EWS for hemoptysis associated with pulmonary MAC infection can be performed safely. PMID- 26879481 TI - Bronchoscopic palliation to treat endobronchial metastasis of the tracheobronchial tree. AB - BACKGROUND: Endobronchial metastases (EBM) are rarely observed, but they are caused by a number of different tumors. Bronchoscopy is the main approach for both differential diagnosis and to maintain endoluminal palliation. In this study, consecutive EBM cases that had been diagnosed and treated were evaluated in a retrospective cohort. METHODS: In total, 18 pathologically verified patients with EBM originating from extrathoracic tumors who were referred to our interventional pulmonology unit with respiratory symptoms were retrospectively evaluated. Tumor type, metastasis location, treatment method and frequency, and complications were evaluated. RESULTS: In total, there were 18 patients (13 women) with EBM enrolled in this study. All were diagnosed by a bronchial biopsy. The mean age of the patients was 48+/-15.24 years (range: 24-76 years). The most frequent sites of origin of the metastases were the bone (5) and kidney. Obstructions were observed in the tracheas of 12 patients, in the right main bronchi of 10, and in the left main bronchi of 11. Twelve airway stents were placed in nine patients. The removal of the obstruction was effective in the remaining patients. The mean number of treatment applications was 1.47 (range: 1 3). Hemorrhage, mucostasis, and granulation were observed. The median follow-up duration was 528 days (range: 62-1177 days). The median survival time for the patients who died was 122 days (range: 2-885 days). CONCLUSIONS: EBM is rare, and bronchoscopy is the primary method of diagnosis, followed by palliation, if necessary. PMID- 26879483 TI - High-flow nasal cannula oxygen therapy for acute exacerbation of interstitial pneumonia: A case series. AB - We report 3 cases (all men, age: 69-81 years) of acute exacerbation of interstitial pneumonia (AEIP) that were successfully treated with a high-flow nasal cannula (HFNC), which delivers heated, humidified gas at a fraction of inspired oxygen (FIO2) up to 1.0 (100%). Oxygenation was insufficient under non rebreathing face masks; however, the introduction of HFNC with an FIO2 of 0.7-1.0 (flow rate: 40 L/min) improved oxygenation and was well-tolerated until the partial pressure of oxygen in blood/FIO2 ratio increased (between 21 and 26 days). Thus, HFNC might be an effective and well-tolerated therapeutic addition to the management of AEIP. PMID- 26879484 TI - Proposed diagnostic criteria for IgG4-related respiratory disease. PMID- 26879485 TI - Multiple nodular pulmonary metastases of lung adenocarcinoma with epidermal growth factor receptor mutation. PMID- 26879486 TI - Neodymium uranyl peroxide synthesis by ion exchange on ammonium uranyl peroxide nanoclusters. AB - This study demonstrates the ability of ammonium uranyl peroxide nanoclusters U32R NH4 to undergo exchange in between NH4(+) and trivalent (Nd(3+)) or tetravalent (Th(4+)) cations in the solid state. It paves the way for new promising routes for the synthesis of mixed uranyl peroxides. The exchange ability may also be considered for solution decontamination and synthesis of new mixed actinide-oxide precursors. Both of these applications could be used in the nuclear industry. PMID- 26879487 TI - Gastrointestinal modifications and bioavailability of brown seaweed phlorotannins and effects on inflammatory markers. AB - Brown seaweeds such as Ascophyllum nodosum are a rich source of phlorotannins (oligomers and polymers of phloroglucinol units), a class of polyphenols that are unique to Phaeophyceae. At present, there is no information on the bioavailability of seaweed polyphenols and limited evidence on their bioactivity in vivo. Consequently, we investigated the gastrointestinal modifications in vitro of seaweed phlorotannins from A. nodosum and their bioavailability and effect on inflammatory markers in healthy participants. In vitro, some phlorotannin oligomers were identified after digestion and colonic fermentation. In addition, seven metabolites corresponding to in vitro-absorbed metabolites were identified. Urine and plasma samples contained a variety of metabolites attributed to both unconjugated and conjugated metabolites (glucuronides and/or sulphates). In both urine and plasma, the majority of the metabolites were found in samples collected at late time points (6-24 h), suggesting colonic metabolism of high-molecular-weight phlorotannins, with three phlorotannin oligomers (hydroxytrifuhalol A, 7-hydroxyeckol, C-O-C dimer of phloroglucinol) identified in urine samples. A significant increase of the cytokine IL-8 was also observed. Our study shows for the first time that seaweed phlorotannins are metabolised and absorbed, predominantly in the large intestine, and there is a large inter individual variation in their metabolic profile. Three phlorotannin oligomers present in the capsule are excreted in urine. Our study is the first investigation of the metabolism and bioavailability of seaweed phlorotannins and the role of colonic biotransformation. In addition, IL-8 is a possible target for phlorotannin bioactivity. PMID- 26879488 TI - An intermediate term benefits and complications of gamma knife surgery in management of glomus jugulare tumor. AB - Glomus tumors are rare skull base slow-growing, hypervascular neoplasms that frequently involve critical neurovascular structures, and delay in diagnosis is frequent. Surgical removal is rarely radical and is usually associated with morbidity or mortality. Gamma knife surgery (GKS) has gained an increasing dependable role in the management of glomus jugulare tumors, with high rate of tumor growth control, preserving or improving clinical status and with limited complications. This study aims to evaluate intermediate term benefits and complications of gamma knife surgery in management of twenty-two patients bearing growing glomus jugulare tumors at the International Medical Center (IMC), Cairo, Egypt, between 2005 and 2011. The mean follow-up period was 56 months (range 36 108 months); there were 3 males, 19 females; mean age was 43.6 years; 15 patients had GKS as the primary treatment; 2 patients had surgical residuals; 2 had previous radiation therapy; and 3 previously underwent endovascular embolization. The average tumor volume was 7.26 cm3, and the mean marginal dose was 14.7 Gy. Post gamma knife surgery through the follow-up period neurological status was improved in 12 patients, 7 showed stable clinical condition and 3 patients developed new moderate deficits. Tumor volume post GKS was unchanged in 13 patients, decreased in 8, and showed tumor regrowth in 1 patient. Tumor progression-free survival in our studied patients was 95.5% at 5 and 7 years of the follow-up period post GKS. Gamma knife surgery could be used safely and effectively with limited complications as a primary management tool in the treatment of glomus jugulare tumors controlling tumor growth with preserving or improving clinical status especially those who do not have significant cranial or cervical extension, elderly, and surgically unfit patients; moreover, it is safe and highly effective as adjuvant therapy as well. PMID- 26879489 TI - Therapeutic Apheresis and Dialysis: 20(th) Year of Publication. PMID- 26879490 TI - Evaluation of Parathyroidectomy for Secondary and Tertiary Hyperparathyroidism by the Parathyroid Surgeons' Society of Japan. AB - Secondary hyperparathyroidism (SHPT) remains a serious complication in patients with chronic kidney disease, and some patients require parathyroidectomy. The Parathyroid Surgeons' Society of Japan (PSSJ) evaluated parathyroidectomy for SHPT and tertiary hyperparathyroidism (THPT) in Japan. The annual numbers of parathyroidectomies between 2004 and 2013 were evaluated using questionnaires. Since 2010, the PSSJ has registered the patients. In total, 826 patients from 42 institutions were registered. The annual number of parathyroidectomies for SHPT and THPT in Japan increased from 2004 to 2007 and then decreased markedly after 2007, with 296 operations performed in 2013. The number of women and men was almost equal (397/427). Median (interquartile range) age of these patients was 59.0 (24-87) years, the duration of hemodialysis before parathyroidectomy was 10.83 (0.0-38.7) years, and diabetic nephropathy was 87/826 (10.5%). Of these patients 59.6% were treated with cinacalcet at undergoing parathyroidectomy. In 75.3% of patients, a total parathyroidectomy with forearm autograft was performed. In 77.7% of patients, four or more parathyroid glands were removed during the initial operation. The incidences of husky voice and wound hemorrhage were 2.9% and 1.1%, respectively. The number of parathyroidectomies for SHPT in Japan decreased markedly after the introduction of cinacalcet. Based on the evaluation of registered patients, parathyroidectomies have been successfully performed at the institutions participating in the PSSJ. PMID- 26879491 TI - New Method for the Approximation of Corrected Calcium Concentrations in Chronic Kidney Disease Patients. AB - The following conventional calcium correction formula (Payne) is broadly applied for serum calcium estimation: corrected total calcium (TCa) (mg/dL) = TCa (mg/dL) + (4 - albumin (g/dL)); however, it is inapplicable to chronic kidney disease (CKD) patients. A total of 2503 venous samples were collected from 942 all-stage CKD patients, and levels of TCa (mg/dL), ionized calcium ([iCa(2+) ] mmol/L), phosphate (mg/dL), albumin (g/dL), and pH, and other clinical parameters were measured. We assumed corrected TCa (the gold standard) to be equal to eight times the iCa(2+) value (measured corrected TCa). Then, we performed stepwise multiple linear regression analysis by using the clinical parameters and derived a simple formula for corrected TCa approximation. The following formula was devised from multiple linear regression analysis: Approximated corrected TCa (mg/dL) = TCa + 0.25 * (4 - albumin) + 4 * (7.4 - p H) + 0.1 * (6 - phosphate) + 0.3. Receiver operating characteristic curves analysis illustrated that area under the curve of approximated corrected TCa for detection of measured corrected TCa >= 8.4 mg/dL and <= 10.4 mg/dL were 0.994 and 0.919, respectively. The intraclass correlation coefficient demonstrated superior agreement using this new formula compared to other formulas (new formula: 0.826, Payne: 0.537, Jain: 0.312, Portale: 0.582, Ferrari: 0.362). In CKD patients, TCa correction should include not only albumin but also pH and phosphate. The approximated corrected TCa from this formula demonstrates superior agreement with the measured corrected TCa in comparison to other formulas. PMID- 26879492 TI - Lactobacillus casei Peritonitis in Peritoneal Dialysis: A Rare Case and Literature Review. PMID- 26879495 TI - Effects of Shewanella putrefaciens on innate immunity and cytokine expression profile upon high stocking density of gilthead seabream specimens. AB - High stocking density increases the number of emerging diseases triggering economic losses worldwide. Probiotics provide an effective and natural solution for preventing some diseases through an improvement of innate immune system among others. In the present work dietary administration of the probiotic Shewanella putrefaciens (known as Pdp11) was evaluated under stress by high stocking density after 2 and 4 weeks of administration to gilthead seabream (Sparus aurata) specimens. Results showed an increase in cellular peroxidase and respiratory burst activity as well as a modulation of cytokine profile when Pdp11 was administered to fish reared at high stocking density. Overall, our results showed how Pdp11 is not only able to improve to some extent the cellular and humoral immunity but also to increase the gene expression profile of pro-inflammatory cytokines such as il1b or il6 in response to high stocking density in gilthead seabream. These findings may support the potential use of this probiotic as functional feed against stress in fish farms. PMID- 26879497 TI - [Not Available]. PMID- 26879496 TI - The ubiquitin ligase SEVEN IN ABSENTIA (SINA) ubiquitinates a defense-related NAC transcription factor and is involved in defense signaling. AB - We recently identified a defense-related tomato (Solanum lycopersicum) NAC (NAM, ATAF1,2, CUC2) transcription factor, NAC1, that is subjected to ubiquitin proteasome system-dependent degradation in plant cells. In this study, we identified a tomato ubiquitin ligase (termed SEVEN IN ABSENTIA3; SINA3) that ubiquitinates NAC1, promoting its degradation. We conducted coimmunoprecipitation and bimolecular fluorescence complementation to determine that SINA3 specifically interacts with the NAC1 transcription factor in the nucleus. Moreover, we found that SINA3 ubiquitinates NAC1 in vitro and promotes NAC1 degradation via polyubiquitination in vivo, indicating that SINA3 is a ubiquitin ligase that ubiquitinates NAC1, promoting its degradation. Our real-time PCR analysis indicated that, in contrast to our previous finding that NAC1 mRNA abundance increases upon Pseudomonas infection, the SINA3 mRNA abundance decreases in response to Pseudomonas infection. Moreover, using Agrobacterium-mediated transient expression, we found that overexpression of SINA3 interferes with the hypersensitive response cell death triggered by multiple plant resistance proteins. These results suggest that SINA3 ubiquitinates a defense-related NAC transcription factor for degradation and plays a negative role in defense signaling. PMID- 26879498 TI - [Not available]. PMID- 26879499 TI - [Not available]. PMID- 26879500 TI - [Not Available]. PMID- 26879501 TI - [Not Available]. PMID- 26879502 TI - Influence of parental perception of school safety and gender on children's physical activity in Mexico: A cross sectional study. AB - OBJECTIVE: This cross sectional study aims to determine the effects of gender and parental perception of safety at school on children's physical activity (PA) levels. MATERIALS AND METHODS: Parents of school aged Mexican children residing in Guadalajara, Mexico City, and Puerto Vallarta, completed surveys about their children's PA measures. The physical activity indicators were evaluated using linear and logistical regression models. RESULTS: Analysis did not indicate that gender moderated the relationship between parental perception of safety and PA measures, but significant gender issues exist with girls participating less than boys in the three measures of PA in this study (p<0.001). CONCLUSION: Results suggest the need for additional interventions promoting physical activity in girls in Mexico. PMID- 26879503 TI - [Satisfaction with life, victimization, and perception of insecurity in Morelos]. AB - OBJECTIVE: To examines the influence of victimization, perceived insecurity and restrictions on daily routines in life satisfaction. MATERIALS AND METHODS: Participants were 7535 (50.2% men) aged between 12 and 60, selected from a proportional stratified sampling. MANOVA and polytomous logistic regression model were calculated. RESULTS: We found significant differences in victimization, perceived insecurity and restrictions on daily routines in relation with life satisfaction levels. Also, physical protective measures, control of personal information, perception of insecurity in public areas and restrictions on daily routines were related to lower levels of satisfaction with life. CONCLUSIONS: Lowest levels of satisfaction with life were associated with victimization, perception of insecurity in public areas, and restrictions on daily routines. PMID- 26879504 TI - [Decrease of HCV seroprevalence in Mexico: Results from the National Health and Nutrition Survey 2012]. AB - OBJECTIVE: To estimate seroprevalence of hepatitis C virus (HCV) among 15-49 years old Mexicans living in households and to describe the profile of seroreactive individuals. MATERIALS AND METHODS: Cross-sectional study implemented in 2012 using a national probabilistic sample with behavioral data from face-to-face interviews at households and HCV antibodies screening using capillary blood from same individuals. RESULTS: HCV seroprevalence in Mexico was estimated at 0.27% (IC95% 0.12-0.60), representing 161 000 persons. Seroprevalence was significantly higher among males (0.45% CI95% 0.01-0.89) than females (0.10% CI95% 0.00-0.22). Multivariate analysis suggests a higher possibility of HCV reactivity among men, increasing with age and higher among those sexually active, and lower for higher socioeconomic level. CONCLUSION: HCV seroprevalence in Mexico by 2012 seems significantly lower than the estimation from 2000 of 1.2% for the same age-group. Evidence of infection among individuals 15-19 years old suggests the need to strength preventive actions, particularly in subjects with risky behaviors. PMID- 26879505 TI - The financial and health burden of diabetic ambulatory care sensitive hospitalisations in Mexico. AB - OBJECTIVE: To estimate the financial and health burden of diabetic ambulatory care sensitive hospitalisations (ACSH) in Mexico during 2001-2011. MATERIALS AND METHODS: We identified ACSH due to diabetic complications in general hospitals run by local health ministries and estimated their financial cost using diagnostic related groups. The health burden estimation assumes that patients would not have experienced complications if they had received appropriate primary care and computes the associated Disability-Adjusted Life Years (DALYs). RESULTS: The financial cost of diabetic ACSH increased by 125% in real terms and their health burden in 2010 accounted for 4.2% of total DALYs associated with diabetes in Mexico. CONCLUSION: Avoiding preventable hospitalisations could free resources within the health system for other health purposes. In addition, patients with ACSH suffer preventable losses of health that should be considered when assessing the performance of any primary care intervention. PMID- 26879506 TI - [Economic recession (2006-2012) and changes in the health status of the Spanish population]. AB - OBJECTIVE: To analyze the relationship of mental health problems in Spanish population with the economic recession (2006-2012), and find out how it affects the self-perception of health status. MATERIALS AND METHODS: Cross-sectional study using the National Health Survey of Spain, 2006/2007 and 2011/2012. Using logistic regression models, three indicators linked to mental health and perceived health were analyzed. RESULTS: In 2011/2012 the consumption of anti anxiety medications and sleeping pills increased in men and women. Mental dysfunction increased during the economic crisis in the male population. The perception of optimal health did not suffer significantly in either men or women. CONCLUSIONS: The economic recession showed a changing relation to the mental and general health of the population, coinciding with an increase in mental health disorders, such as anxiety. PMID- 26879507 TI - [Crohn's disease: The experience of living with a chronic illness]. AB - OBJECTIVE: To explore the experiences of people with Crohn disease (CD), their life-changing events, the impact on their lives and the strategies used to cope with it. MATERIALS AND METHODS: Qualitative study. In-depth interviews were carried out on 10 people affected by the disease in the province of Alicante (Spain). The collection, processing and analysis of data was performed using some phenomenological elements. RESULTS: The experiences of those affected can be classified into four main areas: recognition of the illness; perceived consequences of the disease itself by CD affected patients; disease management, and the search for support. CONCLUSIONS: Knowledge of the life experience of people affected by CD appears to be essential for the effective management of chronic illnesses when planning specific health treatment programs. PMID- 26879508 TI - [Pregnancy under fifteen: The motives and redefinition of life's course]. AB - OBJECTIVES: To interpret the motives of pregnancy in girls and the re signification of their life's course. MATERIALS AND METHODS: In the cities of Bogota, Cali, Cartagena and Medellin, 18 life stories of adolescents under 15 years old with experience of pregnancy were made during 2012 and 2013. A phenomenological analytical framework was used to reveal the motives and meanings. RESULTS: The "because motives" and "in order to motives" of adolescents life course, are redefined by the moral control of families, couples, education and health professionals based on common sense and professional habitus. CONCLUSION: In the real "because motives" it is found that common sense assigns blame and responsibility to teens for their pregnancy. In the educational context there is a device that excludes them and promotes dropouts. In the field of health, human rights abuses are used as a control and punishment mechanism. PMID- 26879509 TI - Costa Rica's implementation of the Framework Convention on Tobacco Control: Overcoming decades of industry dominance. AB - OBJECTIVE: To analyze the passage of Costa Rica's 2012 tobacco control law. MATERIALS AND METHODS: Review of legislation, newspaper articles, and key informant interviews. RESULTS: Tobacco control advocates, in close collaboration with international health groups, recruited national, regional and international experts to testify in the Legislative Assembly, implemented grassroots advocacy campaigns, and generated media coverage to enact strong legislation in March 2012 consistent with the World Health Organization Framework Convention on Tobacco Control, despite tobacco industry lobbying efforts that for decades blocked effective tobacco control legislation. CONCLUSION: Costa Rica's experience illustrates how with resources, good strategic planning, aggressive tactics and perseverance tobacco control advocates can overcome tobacco industry opposition in the Legislative Assembly and Executive Branch. This determined approach has positioned Costa Rica to become a regional leader in tobacco control. PMID- 26879511 TI - Healthcare or sickcare: reestablishing the balance. AB - In this essay we discuss the need to reestablish the balance between health enhancing activities and care for the sick in order to meet the challenges of the 21st century. We first briefly review the historical evolution of personal and public hygiene. We then discuss the increasing emphasis on curative care that has characterized the modern world. We conclude that, in order to meet the emerging challenges, contemporary health systems need to adopt a comprehensive scope which include upstream interventions to address the determinants of health; public health interventions to deal with major risk factors; personal health services to manage common infections, reproductive problems, non-communicable diseases, injuries, and mental health problems; and palliative care to deal with old age and the final phases of the human life cycle. PMID- 26879510 TI - [Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program]. AB - Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination. PMID- 26879512 TI - [Medical elegibility criteria for contraceptive use]. PMID- 26879513 TI - Assessing medication role on neuropathological findings in Parkinson's disease. PMID- 26879515 TI - Structural Collapse of the Hydroquinone-Formic Acid Clathrate: A Pressure-Medium Dependent Phase Transition. AB - The energy landscape governing a new pressure-induced phase transition in the hydroquinone-formic acid clathrate is reported in which the host structure collapses, opening up the cavity channels within which the guest molecules migrate and order. The reversible isosymmetric phase transition causes significant changes in the morphology and the birefringence of the crystal. The subtle intermolecular interaction energies in the clathrate are quantified at varying pressures using novel model energies and energy frameworks. These calculations show that the high-pressure phase forms a more stable host network at the expense of less-stable host-guest interactions. The phase transition can be kinetically hindered using a nonhydrostatic pressure-transmitting medium, enabling the comparison of intermolecular energies in two polymorphic structures in the same pressure range. Overall this study illustrates a need for accurate intermolecular energies when analyzing self-assembly structures and supramolecular aggregates. PMID- 26879514 TI - Nickel-catalysed cyclopropanation of electron-deficient alkenes with diiodomethane and diethylzinc. AB - In the presence of a nickel catalyst, the cyclopropanation of electron-deficient alkenes with diiodomethane and diethylzinc is drastically accelerated. A wide range of cyclopropyl ketones, esters and amides can be accessed under these conditions. PMID- 26879517 TI - Facile Synthesis of Porous Dendritic Bimetallic Platinum-Nickel Nanocrystals as Efficient Catalysts for the Oxygen Reduction Reaction. AB - Certain bimetallic nanocrystals (NCs) possess promising catalytic properties for electrochemical energy conversion. Herein, we report a facile method for the one step synthesis of porous dendritic PtNi NCs in aqueous solution at room temperature that contrasts with the traditional multistep thermal decomposition approach. The dendritic PtNi NCs assembled by interconnected arms are efficient catalysts for the oxygen reduction reaction. This direct and efficient method is favorable for the up-scaled synthesis of active catalysts used in electrochemical applications. PMID- 26879520 TI - Coherently Tunable Triangular Trefoil Phaseonium Metamaterial. AB - Phaseonium is a three-level Lambda quantum system, in which a coherent microwave and an optical control (pump) beams can be used to actively modulate the dielectric response. Here we propose a new metamaterial structure comprising of a periodic array of triangular phaseonium metamolecules arranged as a trefoil. We present a computational study of the spatial distribution of magnetic and electric fields of the probe light and the corresponding transmission and reflection, for various parameters of the optical and microwave beams. For specific values of the probing frequencies and control fields, the phaseonium can display either metallic or dielectric optical response. We find that, in the metallic regime, the phaseonium metamaterial structure supports extremely large transmission, with optical amplification at large enough intensity of the microwave thanks to strong surface plasmon coupling; while, in the dielectric regime without microwave excitation, the transmission bandwidth can be tuned by varying the control beam intensity. Implementation of such phaseonium metamaterial structure in solid-state systems, such as patterned crystals doped with rare-earth elements or dielectric matrices embedded with quantum dots, could enable a new class of actively tunable quantum metamaterials. PMID- 26879518 TI - Leisure time physical activity and the risk of hip or knee replacement due to primary osteoarthritis: a population based cohort study (The HUNT Study). AB - BACKGROUND: The relationship between leisure time physical activity (LPA) and hip and knee OA and subsequent joint replacement has not yet been clearly defined. Some studies have found the risk of knee replacement (TKR) to increase with high levels of LPA, while others have found no overall relationship to either TKR or hip replacement (THR). The aim was to investigate the association between LPA and the risk of severe end-stage OA, defined as THR or TKR due to primary OA, in a large population-based cohort. METHODS: Participants in the Nord-Trondelag Health Study (HUNT) were followed prospectively to identify THR and TKR using the Norwegian Arthroplasty Register. Self-reported LPA was classified as inactive, low, moderate or high. The Cox proportional hazards model was used to calculate hazard ratios (HRs) according to levels of LPA with adjustments for confounding variables. Analyses were performed by age (<45, 45-59 and >=60 years) and sex. RESULTS: A total of 66 964 participants (mean age 46.8 years (SD 16.3) were included in the analyses. We identified 1636 THRs and 1016 TKRs due to primary OA during 17.0 years (median) of follow-up. High LPA was significantly associated with THR for women <45 years (HR 1.78, 95 % CI 1.08-2.94) and men between 45-59 years (HR 1.53, 95 % CI 1.10-2.13) at baseline. A significant trend was found only among women < 45 years at baseline (p = 0.02). We found that LPA was significantly associated with TKR for women only (HR 1.45, 95 % CI 1.03-2.04). No measures of LPA were associated with TKR for men. CONCLUSION: In this population based study, high level of LPA was associated with increased risk of THR where a significant trend of LPA was seen among women <45 years at baseline. For TKR, high LPA was associated with increased risk only in women. In contrast to previous studies, this study shows a possible association between high LPA and the risk of THR. PMID- 26879522 TI - Health professionals' perspectives on children's and young people's participation in health care: a qualitative multihospital study. AB - AIMS AND OBJECTIVES: To investigate healthcare professionals' perspectives on child participation in paediatric hospital care and their opinions on improving participation practices. BACKGROUND: Some scholars argue that the decision-making capacities of children largely depend on the attitudes of healthcare professionals rather than on the children's own competences. Healthcare professionals' perspectives on children's participation in hospital care remain largely unexplored. DESIGN: Qualitative descriptive design. METHODS: Healthcare professionals (n = 32) from 10 paediatric wards in the Netherlands participated in semi-structured interviews. Shier's Pathways to Participation model (2001) was used to guide the interviews. RESULTS: Participation is not a term that is frequently used by professionals; however, they feel familiar with the ideas underlying the term, and it is perceived as being at the core of their work. Professionals believe that high levels of participation are possible in basic care for children. Participation in medical decision-making is considered to be more complex and subject to a number of reservations and restrictions. The participants expressed a strong need to enhance child participation in service evaluation and to increase the respect for and understanding of the rights of children to participate outside of the paediatric unit, including in the surgery and emergency departments. CONCLUSION: Children do not currently participate in the assessment of hospital services. Creative methods that support the role of children in evaluating and improving the quality of paediatric hospital care and services should be developed. Hospital-wide policies could help to promote understanding of child participation among all professionals caring for children in hospitals. RELEVANCE TO CLINICAL PRACTICE: Based on international agreements that the Netherlands has ratified, professionals have the duty to facilitate child participation in hospital care. Concrete opportunities and ideas on how to accomplish this goal in practice are provided, and areas for improvement are identified. PMID- 26879519 TI - An on-chip microfluidic pressure regulator that facilitates reproducible loading of cells and hydrogels into microphysiological system platforms. AB - Coculturing multiple cell types together in 3-dimensional (3D) cultures better mimics the in vivo microphysiological environment, and has become widely adopted in recent years with the development of organ-on-chip systems. However, a bottleneck in set-up of these devices arises as a result of the delivery of the gel into the microfluidic chip being sensitive to pressure fluctuations, making gel confinement at a specific region challenging, especially when manual operation is performed. In this paper, we present a novel design of an on-chip regulator module with pressure-releasing safety microvalves that can facilitate stable gel delivery into designated microchannel regions while maintaining well controlled, non-bursting gel interfaces. This pressure regulator design can be integrated into different microfluidic chip designs and is compatible with a wide variety of gel injection apparatuses operated automatically or manually at different flow rates. The sensitivity and working range of this pressure regulator can be adjusted by changing the width of its pressure releasing safety microvalve design. The effectiveness of the design is validated by its incorporation into a microfluidic platform we have developed for generating 3D vascularized micro-organs (VMOs). Reproducible gel loading is demonstrated for both an automatic syringe pump and a manually-operated micropipettor. This design allows for rapid and reproducible loading of hydrogels into microfluidic devices without the risk of bursting gel-air interfaces. PMID- 26879523 TI - The efficacy of adjuvant radiotherapy in dermatofibrosarcoma protuberans: a systemic review and meta-analysis. AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare and locally aggressive tumour, with a high recurrence rate, even after complete surgical excision. Adjuvant radiotherapy (RT) has been suggested to reduce the risk of local recurrence after inadequate surgical resection in patients with narrow or positive surgical margins. However, the overall efficacy of adjuvant RT has not been well studied because of the rarity of DFSP and lack of an appropriate comparison group. OBJECTIVE: We sought to evaluate the efficacy of adjuvant RT for DFSP by conducting a systemic review and meta-analysis to provide a more evidence-based measure of its effectiveness. METHODS: We conducted a systemic review of articles published before 31 June 2015. Due to the rarity of the disease, we included all studies that reported DFSP patients who received adjuvant RT (postoperatively). The pooled recurrence rates were analysed from these extracted data. RESULTS: Twelve studies met the inclusion criteria. The pooled estimate of the recurrence rate for all adjuvant radiotherapy was 11.74% (95% CI 7.4-17.38; n = 167). Patients with positive/close had a pooled recurrence rate of 14.23% (95% CI 8.13-22.49; n = 92), whereas there was no recurrence in patients with negative margins. The pooled estimate of the recurrence rate between surgery alone and surgery combined with adjuvant radiotherapy showed no significant difference (odds ratio 0.31, P = 0.07), although there was a trend that adjuvant RT had a lower recurrence rate than surgery alone. CONCLUSION: Adjuvant RT might be considered for all patients undergoing surgical excision, even if a negative surgical margin has been achieved. Furthermore, for patients with large or recurrent tumours, especially when wide excision with negative margin would result in a significant functional or cosmetic deficit, postoperative radiotherapy is highly recommended in order to achieve a lower recurrence rate. PMID- 26879525 TI - Freddy on the floor. PMID- 26879526 TI - The anonymity paradox in patient engagement: reputation, risk and web-based public feedback. AB - The UK National Health Service (NHS) has long espoused patient and public engagement. Recent years have seen increasing use of internet-based methods of collecting feedback about patient experience and public and staff views about NHS services and priorities. Often hailed as a means of facilitating participative democratic patient engagement, these processes raise a number of complex issues. A key aspect of it is the opportunity for comment to be made anonymously. Our research reveals an anonymity paradox whereby patients clearly demonstrate a perception that anonymity is a prerequisite for effective use of these feedback processes, whereas professionals demonstrate a perception that patient anonymity is a barrier to effective use. The risks of anonymity are constructed very differently by patients and professionals. Patient concerns around anonymity were not motivated by a general concern about a loss of privacy, but more that a positive identification might compromise future care. For professionals, concerns were voiced more around risks of reputational damage for specific practitioners or practices (in that anyone could say anything) and also that this anonymous feedback was available publicly and that it might go against the medical opinion of the professional. These concerns pointed to important differences in perceptions of patient and professional vulnerability. In the qualitative analysis that follows the key finding was that while anonymity makes service users feel less vulnerable, it can have the opposite effect on managers and clinical staff. This raises important implications for the use and utility of internet-based methods of collecting patient feedback. PMID- 26879524 TI - Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor. AB - Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer. PMID- 26879527 TI - Detecting signatures of positive selection associated with musical aptitude in the human genome. AB - Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and FST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude. PMID- 26879528 TI - Is measurement of TT3 by immunoassay reliable at low concentrations? A comparison of the Roche Cobas 6000 vs. LC-MSMS. AB - OBJECTIVES: Thyroid dysfunction is a common medical condition affecting an estimated 30 million people in the US alone. Employing gold standard Liquid chromatography-tandem mass spectrometry (LC-MSMS) methods we have examined the extent of inaccuracy of immunoassay (IA) measurement for total T3 (TT3) at low, normal and high concentrations. DESIGN AND METHODS: 268 TT3 Roche Cobas 6000 immunoassay TT3 values (covering the low, normal, and high ranges) were compared with LC-MSMS results. RESULTS: At TT3 concentrations between 50 and 113ng/dL (conversion factor for TT3 to SI Units is ng/dL*0.0154=nmol/L), n=122, LC-MSMS values were lower than immunoassay with 72% found to be below the 2.5th percentile by LC-MSMS compared to 27% for immunoassay. Strikingly 45% of the patients classified as normal TT3 by immunoassay were defined as lower than the 2.5th percentile by LC-MSMS. Only 38 of the 122 patients with low T3's were not receiving T4. In this latter group all of whom had TSH's>3.7mIU/L, 74% of results by LC-MSMS were below the 2.5th percentile while only 21% were below the 2.5th percentile by IA. The clinical consequences of these inaccuracies may affect whether dosing with T4 or combination of T4 with T3 is selected for treatment. Finally the correlation of TT3 with TSH was far superior when TT3 was measured by LC-MSMS. A typical case which demonstrates our message is included. CONCLUSION: T3 being the active hormone needs to be reliably measured and if the patient has low TT3 and hypothyroid symptoms persist; treatment with T3 should be considered. A typical case report is included to illustrate the problems of inaccurate immunoassay results for TT3. Measurement of TT3 by immunoassay at low concentrations is less than optimal and often provides the clinician with a normal result when the LC-MSMS method and the patient's clinical condition suggests that supplementation with T3 (as in combination therapy) may be required to optimize patient care. PMID- 26879529 TI - Integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridium acetobutylicum. AB - BACKGROUND: Clostridium acetobutylicum is one of the most important butanol producing strains. However, environmental stress in the fermentation process usually leads to a lower yield, seriously hampering its industrialization. In order to systematically investigate the key intracellular metabolites that influence the strain growth and butanol production, and find out the critical regulation nodes, an integrated analysis approach has been carried out in this study. RESULTS: Based on the gas chromatography-mass spectrometry technology, the partial least square discriminant analysis and the pathway analysis, 40 metabolic pathways linked with 43 key metabolic nodes were identified. In-depth analysis showed that lots of amino acids metabolism promoted cell growth but exerted slight influence on butanol production, while sugar metabolism was favorable for cell growth but unfavorable for butanol synthesis. Besides, both lysine and succinic acid metabolism generated a complex effect on the whole metabolic network. Dicarboxylate metabolism exerted an indispensable role on cell growth and butanol production. Subsequently, rational feeding strategies were proposed to verify these conclusions and facilitate the butanol biosynthesis. Feeding amino acids, especially glycine and serine, could obviously improve cell growth while yeast extract, citric acid and ethylene glycol could significantly enhance both growth and butanol production. CONCLUSIONS: The feeding experiment confirmed that metabolic profiling combined with pathway analysis provided an accurate, reasonable and practical approach to explore the cellular metabolic activity and supplied a basis for improving butanol production. These strategies can also be extended for the production of other important bio-chemical compounds. PMID- 26879533 TI - Milestones in Investigative Dermatology: The Desmosome. PMID- 26879530 TI - Modelling severe Staphylococcus aureus sepsis in conscious pigs: are implications for animal welfare justified? AB - BACKGROUND: A porcine model of haematogenous Staphylococcus aureus sepsis has previously been established in our research group. In these studies, pigs developed severe sepsis including liver dysfunction during a 48 h study period. As pigs were awake during the study, animal welfare was challenged by the severity of induced disease, which in some cases necessitated humane euthanasia. A pilot study was therefore performed in order to establish the sufficient inoculum concentration and application protocol needed to produce signs of liver dysfunction within limits of our pre-defined humane endpoints. METHODS: Four pigs received 1 * 10(8) cfu/kg BW of S. aureus, and two controls were sham inoculated with saline. A fixed infusion rate of 3 mL/min was used, while the inoculum concentration, i.e., the dose volume, was changed between the pigs. The following dose volumes were used: 10 mL (n = 1), 20 mL (n = 2), and 30 mL (n = 1), corresponding to infusion durations of 3.33, 6.66, and 10 min at dose rates of 3 * 10(7), 1.5 * 10(7), and 1 * 10(7) cfu/min/kg BW, respectively. Blood samples were drawn for complete blood count, clinical chemistry, and inflammatory markers before and every 6 h after inoculation. Prior to euthanasia, a galactose elimination capacity test was performed to assess liver function. Pigs were euthanised 48 h post inoculation for necropsy and histopathological evaluation. RESULTS: While infusion times of 6.66 min, and higher, did not induce liver dysfunction (n = 3), the infusion time of 3.33 min (n = 1) caused alterations in parameters similar to what had been seen in our previous studies, i.e., increasing bilirubin and aspartate aminotransferase, as well as histopathological occurrence of intravascular fibrin split products in the liver. This pig was however euthanised after 30 h, according to humane endpoints. CONCLUSIONS: A usable balance between scientific purpose and animal welfare could not be achieved, and we therefore find it hard to justify further use of this conscious porcine sepsis model. In order to make a model of translational relevance for human sepsis, we suggest that future model versions should use long-term anaesthesia. PMID- 26879531 TI - Interaction between MTHFR 677C>T and periconceptional folic acid supplementation in the risk of Hypospadias. AB - BACKGROUND: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the development of hypospadias is unclear. As folate levels may also be influenced by the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, we hypothesize that a gene-environment interaction between this polymorphism and folic acid use is involved in the etiology of hypospadias. METHODS: We conducted a case-control study among 855 hypospadias cases and 713 population-based controls from the AGORA data- and biobank. Folic acid supplement use was derived from maternal questionnaires and infant and maternal DNA was used to determine the MTHFR C677T polymorphism using Taqman assays. We performed separate analyses for different hypospadias phenotypes (anterior/middle/posterior). RESULTS: Hypospadias was neither associated with folic acid use or the MTHFR C677T polymorphism, nor with their interaction. However, we did find an association with middle hypospadias when no supplements were used (odds ratio = 1.6; 95% confidence interval, 1.1-2.4), especially in infants carrying the CT/TT genotype (odds ratio = 2.5; 95% confidence interval, 1.4-4.7). In addition, more infants with these genotypes seemed to have posterior hypospadias, regardless of folic acid use. CONCLUSION: Our study does not suggest a major role for folic acid supplements or the MTHFR C677T polymorphism in the etiology of hypospadias in general, but not using folic acid and/or carrying the MTHFR C677T polymorphism may be associated with middle and posterior hypospadias. Therefore, we stress the importance of studying gene-environment interactions preferably in stratified analyses for different hypospadias phenotypes. PMID- 26879534 TI - Desmogleins and Desmocollins as Adhesive Molecules. PMID- 26879532 TI - Whole genome resequencing of the human parasite Schistosoma mansoni reveals population history and effects of selection. AB - Schistosoma mansoni is a parasitic fluke that infects millions of people in the developing world. This study presents the first application of population genomics to S. mansoni based on high-coverage resequencing data from 10 global isolates and an isolate of the closely-related Schistosoma rodhaini, which infects rodents. Using population genetic tests, we document genes under directional and balancing selection in S. mansoni that may facilitate adaptation to the human host. Coalescence modeling reveals the speciation of S. mansoni and S. rodhaini as 107.5-147.6KYA, a period which overlaps with the earliest archaeological evidence for fishing in Africa. Our results indicate that S. mansoni originated in East Africa and experienced a decline in effective population size 20-90KYA, before dispersing across the continent during the Holocene. In addition, we find strong evidence that S. mansoni migrated to the New World with the 16-19th Century Atlantic Slave Trade. PMID- 26879535 TI - Skin Needs Plakophilin-1. PMID- 26879536 TI - Desmoplakin Is Essential for Epidermal Sheet Formation. PMID- 26879537 TI - High-Resolution Mapping of the Desmosomal Plaque and Adhesive Interface. PMID- 26879538 TI - Identification of Desmogleins as Disease Targets. PMID- 26879539 TI - Spotting Desmosomes: The First 100 Years. PMID- 26879540 TI - Biochemical Characterization of the Desmosome. PMID- 26879541 TI - Identification of Desmoglein as a Cadherin and Analysis of Desmoglein Domain Structure. PMID- 26879542 TI - Making Connections: Desmoplakin as an Intermediate Filament-Binding Protein. PMID- 26879543 TI - Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway. AB - Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function. PMID- 26879544 TI - Strong resilience of soil respiration components to drought-induced die-off resulting in forest secondary succession. AB - How forests cope with drought-induced perturbations and how the dependence of soil respiration on environmental and biological drivers is affected in a warming and drying context are becoming key questions. The aims of this study were to determine whether drought-induced die-off and forest succession were reflected in soil respiration and its components and to determine the influence of climate on the soil respiration components. We used the mesh exclusion method to study seasonal variations in soil respiration (R S) and its components: heterotrophic (R H) and autotrophic (R A) [further split into fine root (R R) and mycorrhizal respiration (R M)] in a mixed Mediterranean forest where Scots pine (Pinus sylvestris L.) is undergoing a drought-induced die-off and is being replaced by holm oak (Quercus ilex L.). Drought-induced pine die-off was not reflected in R S nor in its components, which denotes a high functional resilience of the plant and soil system to pine die-off. However, the succession from Scots pine to holm oak resulted in a reduction of R H and thus in an important decrease of total respiration (R S was 36 % lower in holm oaks than in non-defoliated pines). Furthermore, R S and all its components were strongly regulated by soil water content-and-temperature interaction. Since Scots pine die-off and Quercus species colonization seems to be widely occurring at the driest limit of the Scots pine distribution, the functional resilience of the soil system over die-off and the decrease of R S from Scots pine to holm oak could have direct consequences for the C balance of these ecosystems. PMID- 26879545 TI - Feasibility of weekly intraperitoneal versus intravenous paclitaxel therapy delivered from the day of radical surgery for gastric cancer: a preliminary safety analysis of the INPACT study, a randomized controlled trial. AB - BACKGROUND: Peritoneal carcinomatosis is common after curative resection of gastric cancer. Intraperitoneal administration of paclitaxel (PTX) is known to control ovarian peritoneal metastases. PATIENTS AND METHODS: Patients with either linitis plastica or T4 cancer with high risk of peritoneal metastasis or recurrence but whose cancer was considered resectable were preregistered. After their cancer had been confirmed intraoperatively as resectable, the patients were randomized into either group A (PTX at 60 mg/m2 intraperitoneally on the day of surgery and on days 14, 21, 28, 42, 49, and 56) or group B (PTX at 80 mg/m2 administered intravenously by the identical schedule) before being treated by evidence-based chemotherapy. The primary end point was the 2-year survival rate. Safety, the secondary end point, was also analyzed. The study has been registered as UMIN000002957. RESULTS: Of 177 preregistered patients, 83 underwent treatment (39 by intraperitoneal administration and 44 by intravenous administration). There was no difference in patient demographics between the two groups. The incidences of surgical complications were similar between the groups, except for transient bowel obstruction observed exclusively in group A. The relative dose intensity of PTX was 81.4 % for group A and 76.3 % for group B. There was one death due to pulmonary thrombosis and a case of anaphylaxis that led to termination of the protocol treatment (group B). Other adverse events were mild and manageable. CONCLUSIONS: Intraperitoneal administration of PTX from the day of gastrectomy did not result in a higher incidence of surgical complications and adverse reactions when compared with intravenous administration of PTX. PMID- 26879546 TI - Quality of Life and Long-Term Therapy in Patients with Chronic Myeloid Leukemia. AB - Since the development of imatinib and other tyrosine kinase inhibitors (TKIs), the prognosis for patients with chronic myeloid leukemia (CML) has markedly improved, such that most patients diagnosed with CML can now expect to live with their disease rather than die from it. However, most patients will require long term treatment, which has deleterious effects on health-related quality of life. We review recent literature on drug-related adverse effects, long-term medication adherence, limitations to fertility and pregnancy, effects on cognitive function, ability to work, financial toxicity, pediatric populations, and treatment discontinuation. While patients with CML are fortunate to have excellent therapies available to control their disease, many are unable to lead normal lives, which challenges the notion that research is no longer needed in CML. Curing CML, i.e., no detectable disease and no need for daily medications, should remain the ultimate goal. PMID- 26879547 TI - Fluorescent copper nanoparticles: recent advances in synthesis and applications for sensing metal ions. AB - Fluorescent copper nanoparticles (F-CuNPs) have received great attention due to their attractive features, such as water solubility, wide availability, ease of functionalization and good biocompatibility, and considerable efforts have been devoted to the preparation and applications of F-CuNPs. This review article comprises three main parts. In the first part, we briefly present the fluorescence properties of F-CuNPs. Then we cover the fabrication strategies of various F-CuNPs functionalized by different ligands. In the third part, we focus on the applications of F-CuNPs for sensing metal ions, including Hg(2+), Pb(2+), Cu(2+), Fe(3+) and other metal ions. Lastly, we further discuss the opportunities and challenges of F-CuNPs in the synthetic strategies and applications for sensing metal ions. PMID- 26879548 TI - In Response to: Heparin Binding-Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice. PMID- 26879549 TI - Aromatase inhibitors with or without luteinizing hormone-releasing hormone agonist for metastatic male breast cancer: report of four cases and review of the literature. AB - The roles of aromatase inhibitors (AIs) and luteinizing hormone-releasing hormone (LH-RH) agonists in the management of male breast cancer remain uncertain, with no reports in Japanese men. We report four Japanese male patients with metastatic breast cancer treated with AIs with or without an LH-RH agonist, and consider the relationship between treatment effect and estradiol (E2) concentration. Three patients were initially treated with AI alone after selective estrogen receptor modulators (SERMs), and one received AIs plus an LH-RH agonist after a SERM. Two patients treated with an AI alone responded, one patient with E2 levels below the lower assay limit and the other with levels above the limit. The other treated with an AI alone experienced progression regardless of the E2 levels below the lower assay limit, however, responded after the addition of an LH-RH agonist. E2 concentrations were related to the efficacy of treatment in one patient. The patient initially treated with an AI plus an LH-RH agonist also responded. No grade 3 or 4 adverse events were observed in any of the patients treated with AIs with or without an LH-RH agonist. AIs with or without an LH-RH agonist offer an effective treatment option for hormone receptor-positive metastatic male breast cancer. PMID- 26879550 TI - Oral epithelial cells and their interactions with HIV-1. AB - As the AIDS pandemic has continued, our understanding of the events that occur during the entry and infection of conventional, susceptible cells has increased dramatically, leading to the development of control therapies for HIV-infected individuals. However, an ongoing hole in our understanding is how HIV crosses the mucosal barriers to gain access to permissive cells, despite how important this information would be in developing successful vaccines and other preventative measures such as topical anti-HIV microbicides. In particular, our knowledge of the role that epithelial cells of the mucosal surfaces play in infection - both during early phases and throughout the life of an infected individual, is currently hazy at best. However, several studies in recent years suggest that HIV can bind to and traverse these mucosal epithelial cells, providing a reservoir of infection that can subsequently infect underlying permissive cells. Despite this interaction with epithelial cells, evidence suggests HIV-1 does not productively infect these cells, although they are capable of transferring surface-bound and transcytosed virus to other, permissive cells. Further, there appear to be key differences between adult and infant epithelial cells in the degree to which HIV can transcytose and infect the epithelium. Thus, it is clear that, whilst not primary targets for infection and virus replication, epithelial cells play an important role in the infection cycle and improving our understanding of their interactions with HIV could potentially provide key insights necessary to develop effective preventative therapies. PMID- 26879551 TI - Diagnosis of Obscure Gastrointestinal Bleeding. AB - Obscure gastrointestinal bleeding (OGIB) is defined as gastrointestinal bleeding from a source that cannot be identified on upper or lower gastrointestinal endoscopy. OGIB is considered an important indication for capsule endoscopy (CE). CE is particularly useful for the detection of vascular and small ulcerative lesions, conditions frequently associated with OGIB, particularly in Western countries. On the other hand, balloon enteroscopy (BE) can facilitate the diagnosis of lesions presenting with minimal changes of the mucosal surface, such as submucosal tumors, and can be used not only for diagnosis, but also for treatment, including endoscopic hemostasis. In other words, the complementary use of both CE and BE enables OGIB to be more efficiently diagnosed and treated. However, rebleeding can occur even in patients with negative results of CE, and such patients require repeat CE or BE. It is essential to effectively use both CE and BE based on a thorough understanding of the strong points and weak points of these procedures. Further advances and developments in virtual endoscopy incorporating computed tomography and magnetic resonance imaging are expected in the future. PMID- 26879552 TI - Endoscopic Submucosal Dissection for Early Gastric Neoplasia Occurring in the Remnant Stomach after Distal Gastrectomy. AB - BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) for tumors occurring in the remnant stomach is technically difficult to perform because of limited working space and severe fibrosis and staples present around the suture line. We aimed to elucidate the feasibility and clinical outcomes of performing ESD for tumors in the remnant stomach. METHODS: Between December 2007 and January 2013, 18 patients underwent ESD for tumors (six adenomas and 12 differentiated-type early gastric cancers [EGCs]) occurring in the remnant stomach after distal gastrectomy. Clinicopathologic features and clinical outcomes after ESD were retrospectively analyzed. RESULTS: Two-thirds of the lesions were located on the body, and half were located on the suture line. En bloc resection, R0 resection, and en bloc with R0 resection rates were 88.9%, 100%, and 88.9%, respectively. Curative resection rate for EGC was 91.7%. Perforation occurred in one patient (5.6%) and was successfully managed by endoscopic closure with metallic clips and conservative management. There was no significant bleeding after ESD. During a median follow-up of 47.5 months, no local, metachronous, or extragastric recurrence was seen for either EGC or adenoma lesions. CONCLUSIONS: ESD is a feasible and effective treatment modality and can be considered a primary intervention for early gastric neoplasia occurring in the remnant stomach. PMID- 26879553 TI - Tracheal Involvement in Crohn Disease: the First Case in Korea. AB - Respiratory involvement in Crohn disease (CD) is rare condition with only about a dozen reported cases. We report the first case of CD with tracheal involvement in Korea. An 18-year-old woman with CD was hospitalized because of coughing, dyspnea, and fever sustained for 3 weeks. Because she had stridor in her neck, we performed computed tomography of the neck, which showed circumferential wall thickening of the larynx and hypopharynx. Bronchoscopy revealed mucosal irregularity, ulceration, and exudates debris in the proximal trachea, and bronchial biopsy revealed chronic inflammation with granulation tissue. Based on these findings, we suspected CD with tracheal involvement and began administering intravenous methylprednisolone at 1 mg/kg per day, after which her symptoms and bronchoscopic findings improved. PMID- 26879554 TI - Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics. AB - Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car-Parrinello molecular dynamics simulations. Proton transfer (PT) occurs to form an aqueous solvent stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid-base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pKa difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen's charge from approximately midway between that of a hydrogen atom and that of a proton. PMID- 26879555 TI - [Intravitreal dexamethasone implant for treatment of persistent postoperative macular edema after vitrectomy]. AB - BACKGROUND: To date, there is no consensus about the management of persistent cystoid macular edema (CME) following vitrectomy. The aim of this study was to evaluate the efficacy and safety of intravitreal dexamethasone implants for the treatment of postoperative CME following vitrectomy. MATERIAL AND METHODS: In this multicenter study we retrospectively reviewed the data of 24 patients (25 eyes) who had been treated with intravitreal dexamethasone (Ozurdex(r)) for the management of persistent postoperative CME following pars plana vitrectomy. The main outcome measure was central retinal thickness (CRT in um) as assessed by spectral domain optical coherence tomography (SD-OCT). Secondary outcome measures included change in best corrected visual acuity (BCVA) and the presence of metamorphopsia. RESULTS: All 19 eyes which were postoperatively examined within 4 8 weeks after implantation showed a significant decrease in CRT (mean 564 um to 315 um) and a reduction of metamorphopsias. Within the same period of time the BCVA improved in 15 out of 19 eyes (79%) which corresponds to an average visual improvement from 0.69 logMAR to 0.46 logMAR (P <0.0001). In eyes examined after 10-16 weeks a slight increase in the average CRT of 351 um was observed, whereas the BCVA improved to 0.28 logMAR. After 4 months a decrease in average BCVA was noted. Out of 25 eyes 12 required further dexamethasone implantations between 1 and 4 times within the investigation period. The first repeat injections were performed an average of 7.3 months after the initial treatment. CONCLUSION: Our results suggest that intravitreal dexamethasone is a safe and effective treatment option for persistent CME following vitrectomy. PMID- 26879556 TI - [Pediatric conjunctival tumor with cilia]. PMID- 26879557 TI - [Sympathetic ophthalmia : Therapy with steroid-free immunosuppressant azathioprine]. AB - This article describes the case of a 48-year-old male patient who presented with persistent inflammation and deterioration of vision to a best corrected visual acuity (BCVA) of 0.6 in the only functioning left eye. The right eye had suffered a severe penetrating ocular trauma 6 months prior to presentation. After diagnosis of a sympathetic ophthalmia a high dosage corticosteroid therapy was initiated. Due to intolerance with decompensating diabetes an immunosuppressive therapy with azathioprine was initiated. This therapy resulted in stable clinical findings with an increase in BCVA to 0.9. PMID- 26879558 TI - Cultural Studies Methodologies and Narrative Family Therapy: Therapeutic Conversations About Pop Culture. AB - Therapists recognize that popular media culture is an influential force that shapes identities and relationships in contemporary society. Indeed, people have serious relationships with the commodities and practices that emerge from pop culture. However, they often lack the conceptual and conversational resources to engage meaningfully with clients about pop culture's influence in their lives. Cultural studies is introduced as an interdisciplinary approach that provides frameworks for both theory and practice that position therapists and clients to critically examine the role of pop culture in their lives. Cultural studies and narrative therapy are discussed as praxis allies that share a populist political intention and counter-hegemonic discursive practices. The integration of cultural studies methodologies into narrative therapy practice with a parent and her teenage daughter is illustrated through a case vignette. PMID- 26879559 TI - Interleukin-6-stimulated progranulin expression contributes to the malignancy of hepatocellular carcinoma cells by activating mTOR signaling. AB - This study aimed to determine the expression of progranulin (PGRN) in hepatocellular carcinoma (HCC) cells in response to interleukin 6 (IL-6), a non cellular component of the tumor microenvironment, and the molecular mechanism of PGRN oncogenic activity in hepatocarcinogenesis. Levels of IL-6 and PGRN were increased and positively correlated in HCC tissues. IL-6 dose- and time dependently increased PGRN level in HCC cells. IL-6-driven PGRN expression was at least in part mediated by Erk/C/EBPbeta signaling, and reduced expression of PGRN impaired IL-6-stimulated proliferation, migration and invasion of HepG2 cells. PGRN activated mammalian target of rapamycin (mTOR) signaling, as evidenced by increased phosphorylation of p70S6K, 4E-BP1, and Akt-Ser473/FoxO1. Inhibition of mTOR signaling with rapamycin, an mTOR signaling inhibitor, disturbed PGRN- or IL 6-mediated proliferation, migration and invasion of HCC cells in vitro. Persistent activation of mTOR signaling by knockdown of TSC2 restored PGRN knockdown-attenuated pro-proliferation effects of IL-6 in HepG2 cells. In addition, rapamycin treatment in vivo in mice slowed tumor growth stimulated by recombinant human PGRN. Our findings provide a better understanding of the biological activities of the IL-6/PGRN/mTOR cascade in the carcinogenesis of HCC, which may suggest a novel target in the treatment of HCC. PMID- 26879560 TI - Evidence of Misclassification of Drug-Event Associations Classified as Gold Standard 'Negative Controls' by the Observational Medical Outcomes Partnership (OMOP). AB - INTRODUCTION: Pharmacovigilance includes analysis of large databases of information on drugs and events using algorithms that detect disproportional frequencies of associations. In order to test such algorithms, attempts have been made to provide canonical reference lists of so-called 'positive controls' and 'negative controls'. Reference sets with even modest levels of misclassification may result in under- or overstatement of the performance of algorithms. AIM: We sought to determine the extent to which 'negative control' drug-event pairs in the Observational Medical Outcomes Partnership (OMOP) database are misclassified METHODS: We searched the medical literature for evidence of associations between drugs and events listed by OMOP as negative controls. RESULTS: The criteria used in OMOP to classify positive and negative controls are asymmetric; drug-event associations published only as case series or case reports are classified as positive controls if they are cited in Drug-Induced Diseases by Tisdale and Miller, but as negative controls if case series or case reports exist but are not cited in Tisdale and Miller. Of 233 drug-event pairs classified in the 2013 version of OMOP as negative controls, 21 failed to meet pre-specified OMOP adjudication criteria; in another 19 cases we found case reports, case series, or observational evidence that the drug and event are associated. Overall, OMOP misclassified, or may have misclassified, 40 (17 %) of all 'negative controls.' CONCLUSIONS: Results from studies of the performance of signal-detection algorithms based on the OMOP gold standard should be viewed with circumspection, because imperfect gold standards may lead to under/overstatement of absolute and relative signal detection algorithm performance. Improvements to OMOP would include omitting misclassified drug-event pairs, assigning more specific event labels, and using more extensive sources of information. PMID- 26879561 TI - Modulation of oligodendrocyte differentiation and maturation by combined biochemical and mechanical cues. AB - Extracellular matrix (ECM) proteins play a key role during oligodendrogenesis. While fibronectin (FN) is involved in the maintenance and proliferation of oligodendrocyte progenitor cells (OPCs), merosin (MN) promotes differentiation into oligodendrocytes (OLs). Mechanical properties of the ECM also seem to affect OL differentiation, hence this study aimed to clarify the impact of combined biophysical and biochemical elements during oligodendrocyte differentiation and maturation using synthetic elastic polymeric ECM-like substrates. CG-4 cells presented OPC- or OL-like morphology in response to brain-compliant substrates functionalised with FN or MN, respectively. The expression of the differentiation and maturation markers myelin basic protein--MBP--and proteolipid protein--PLP- (respectively) by primary rat oligodendrocytes was enhanced in presence of MN, but only on brain-compliant conditions, considering the distribution (MBP) or amount (PLP) of the protein. It was also observed that maturation of OLs was attained earlier (by assessing PLP expression) by cells differentiated on MN functionalised brain-compliant substrates than on standard culture conditions. Moreover, the combination of MN and substrate compliance enhanced the maturation and morphological complexity of OLs. Considering the distinct degrees of stiffness tested ranging within those of the central nervous system, our results indicate that 6.5 kPa is the most suitable rigidity for oligodendrocyte differentiation. PMID- 26879562 TI - Open Versus Closed Hearing-Aid Fittings: A Literature Review of Both Fitting Approaches. AB - One of the main issues in hearing-aid fittings is the abnormal perception of the user's own voice as too loud, "boomy," or "hollow." This phenomenon known as the occlusion effect be reduced by large vents in the earmolds or by open-fit hearing aids. This review provides an overview of publications related to open and closed hearing-aid fittings. First, the occlusion effect and its consequences for perception while using hearing aids are described. Then, the advantages and disadvantages of open compared with closed fittings and their impact on the fitting process are addressed. The advantages include less occlusion, improved own-voice perception and sound quality, and increased localization performance. The disadvantages associated with open-fit hearing aids include reduced benefits of directional microphones and noise reduction, as well as less compression and less available gain before feedback. The final part of this review addresses the need for new approaches to combine the advantages of open and closed hearing-aid fittings. PMID- 26879563 TI - Exponentially growing osteosarcoma of mandible with acromegaly. AB - BACKGROUND: Osteosarcoma of the head and neck is aggressive malignancy that might be affected by growth hormone. The purpose of this study was to demonstrate an unusual case of osteosarcoma with acromegaly. METHODS AND RESULTS: This case is about a 39-year-old woman with an osteosarcoma of the mandible, who had a history of exponential tumor growth in spite of chemotherapy at another hospital. She transferred to Samsung Medical Center and underwent a wide resection of tumor and free flap reconstruction. During postoperative care, a brain MRI and hormonal test revealed a growth hormone-secreting pituitary adenoma, and then a transsphenoidal approach pituitary tumor removal was performed. Immunohistochemistry of the osteosarcoma indicated positive for insulin-like growth factor (IGF)-2 and somatostatin receptor. CONCLUSION: This study proved the IGF-2 and somatostatin receptor from the osteosarcoma of the patient with acromegaly, and this could explain that the growth hormone secreting from the pituitary adenoma might be a risk factor of therapeutic intractability and growth acceleration of osteosarcoma. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2432-E2436, 2016. PMID- 26879565 TI - Zika and microcephaly in Latin America: An emerging threat for pregnant travelers? PMID- 26879564 TI - Positive and negative staircase effect during single twitch and train-of-four stimulation: a laboratory study in dogs. AB - A positive staircase effect is well documented during neuromuscular monitoring. However, the increase in twitch amplitude may not remain stable over time. We compared the staircase phenomenon and twitch stability during single twitch (ST) or train-of-four (TOF) stimulation in anesthetized dogs. Force of contraction was measured in ten dogs. Each thoracic limb was stimulated with ST 0.1 Hz or TOF q 12 s for 25 min (random order). No neuromuscular blockers were administered. Every 5 min, ST and T1 amplitudes were compared within and between groups. Stability of twitch amplitude (<5 % change in 5 min) was also evaluated. ST and T1 amplitude increased over time without significant differences between groups. After 10 min of ST stimulation, the average ST amplitude had increased significantly to 107 %, and remained unchanged thereafter. T1 amplitude was significantly greater than baseline only at 5 (111 %) and 10 min (109 %); a decline towards baseline occurred thereafter. Stability was reached after 15 min for all dogs in the ST group, however, three dogs continued to have changes >5 % with TOF. An initial increase in ST amplitude remained stable over the observation period, but the increase in T1 amplitude during TOF was frequently followed by a decay. A stable twitch amplitude (variation <5 % in 5 min) was observed in all dogs with ST after 15 min of stimulation, which was not the case during TOF stimulation. Therefore, it appears at least in dogs, that ST might offer some advantages over T1 for measuring twitch amplitude. PMID- 26879566 TI - Aedes and the triple threat of DENV, CHIKV, ZIKV--Arboviral risks and prevention at the 2016 Rio Olympic games. PMID- 26879567 TI - The relationship between resting heart rate and peak VO2: A comparison of atrial fibrillation and sinus rhythm. AB - BACKGROUND: Resting heart rate is a surrogate marker associated with achieved exercise capacity, which has been observed in patients with sinus rhythm. The aim of this study was to examine and compare the relationships between resting heart rate and peak oxygen consumption in atrial fibrillation and sinus rhythm. METHODS AND RESULTS: A total of 2160 consecutive patients undergoing cardiopulmonary exercise testing in our single-hospital cohort were divided into two groups according to rhythm status: an atrial fibrillation group (N = 320) and a sinus rhythm group (N = 1840). In the total cohort and sinus rhythm group, resting heart rate was negatively correlated with percentage of predicted peak oxygen consumption (Ptrend < 0.0001); in atrial fibrillation patients, this correlation was apparently positive (Ptrend = 0.032). Multivariate analysis of the total cohort showed a significant interaction between resting heart rate and rhythm status for peak oxygen consumption after adjustments for age, sex, ejection fraction, structural heart diseases and heart rate-lowering drugs. In the sinus rhythm group, resting heart rate was an independent, negative contributing factor for peak oxygen consumption, even after the adjustments for patient background. However, in the atrial fibrillation group, resting heart rate was a weak positive or non-independent contributing factor for peak oxygen consumption after the same adjustments. CONCLUSIONS: The impact of resting heart rate on exercise capacity differed completely between atrial fibrillation and sinus rhythm, suggesting that heart rate control may need to be managed differently for atrial fibrillation and sinus rhythm, in light of exercise capacity that is related to quality of life and prognosis. PMID- 26879568 TI - High-grade carotid artery stenosis: A forgotten area in cardiovascular risk management. AB - BACKGROUND: Patients with high-grade (>=70%) carotid artery stenosis (CAS) rank in the highest risk category for future cardiovascular (CV) events, but the quality of cardiovascular risk management in this patient group is unknown. DESIGN: Cross-sectional retrospective study. METHODS: Data were collected for all patients diagnosed with high-grade CAS in Ostergotland county, Sweden between 1 January 2009 and 31 July 2012 regarding the quality of cardiovascular risk management, co-morbidity and outcomes during the 2-year follow-up period after a diagnosis of CAS with a carotid ultrasound scan. Patients were included regardless of whether they underwent carotid endarterectomy (CEA). RESULTS: A total of 393 patients with CAS were included in the study; 133 (33.8%) underwent CEA and 260 (66.2%) were assigned to a conservative management (CM) group. In both groups of patients the prescription of platelet inhibitors, statins and antihypertensive drugs increased significantly (p < 0.001) after diagnosis. However treatment targets were not met in the majority of patients and the low density lipoprotein level was on target in only 13.5% of patients. During follow up, low-density lipoprotein levels were not measured in 19.8% of patients who underwent CEA and 44.2% of patients in the CM group (p < 0.001); HbA1c was not measured in 24.4% of patients with diabetes in the CEA group and in 18.8% of patients in the CM group (p = 0.560). There was no documentation of counselling on diet, exercise, smoking cessation or adherence to medication. The combined clinical event rate (all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events) was high in both groups (CEA 36.8% and CM 36.9%; p = 1.00) with no difference in the occurrence of ipsilateral ischaemic stroke. CONCLUSIONS: The clinical event rate was high in patients with high-grade CAS and the management of cardiovascular risk was deficient in all aspects. PMID- 26879571 TI - A novel role for Crp in controlling magnetosome biosynthesis in Magnetospirillum gryphiswaldense MSR-1. AB - Magnetotactic bacteria (MTB) are specialized microorganisms that synthesize intracellular magnetite particles called magnetosomes. Although many studies have focused on the mechanism of magnetosome synthesis, it remains unclear how these structures are formed. Recent reports have suggested that magnetosome formation is energy dependent. To investigate the relationship between magnetosome formation and energy metabolism, a global regulator, named Crp, which mainly controls energy and carbon metabolism in most microorganisms, was genetically disrupted in Magnetospirillum gryphiswaldense MSR-1. Compared with the wild-type or complemented strains, the growth, ferromagnetism and intracellular iron content of crp-deficient mutant cells were dramatically decreased. Transmission electron microscopy (TEM) showed that magnetosome synthesis was strongly impaired by the disruption of crp. Further gene expression profile analysis showed that the disruption of crp not only influenced genes related to energy and carbon metabolism, but a series of crucial magnetosome island (MAI) genes were also down regulated. These results indicate that Crp is essential for magnetosome formation in MSR-1. This is the first time to demonstrate that Crp plays an important role in controlling magnetosome biomineralization and provides reliable expression profile data that elucidate the mechanism of Crp regulation of magnetosome formation in MSR-1. PMID- 26879572 TI - Decompressive craniectomy in neurocritical care. AB - Recently, several randomized controlled trials (RCT) investigating the effectiveness of decompressive craniectomy in the context of neurocritical illnesses have been completed. Thus, a meta-analysis to update the current evidence regarding the effects of decompressive craniectomy is necessary. We searched PUBMED, EMBASE and the Cochrane Central Register of Controlled Trials. Other sources, including internet-based clinical trial registries and grey literature, were also searched. After searching the literature, two investigators independently performed literature screening, assessing the quality of the included trials and extracting the data. The outcome measures included the composite outcome of death or dependence and the risk of death. Ten RCT were included: seven RCT were on malignant middle cerebral artery infarction (MCAI) and three were on severe traumatic brain injury (TBI). Decompressive craniectomy significantly reduced the risk of death for patients suffering malignant MCAI (risk ratio [RR] 0.46, 95% confidence interval [CI]: 0.36-0.59, P<0.00001) in comparison with no reduction in the risk of death for patients with severe TBI (RR: 0.83, 95% CI: 0.48-1.42, P=0.49). However, there was no significant difference in the composite risk of death or dependence at the final follow-up between the decompressive craniectomy group and the conservative treatment group for either malignant MCAI or severe TBI. The present meta-analysis indicates that decompressive craniectomy can significantly reduce the risk of death for patients with malignant MCAI, although no evidence demonstrates that decompressive craniectomy is associated with a reduced risk of death or dependence for TBI patients. PMID- 26879574 TI - Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/beta-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26879573 TI - Hepatic circadian clock oscillators and nuclear receptors integrate microbiome derived signals. AB - The liver is a key organ of metabolic homeostasis with functions that oscillate in response to food intake. Although liver and gut microbiome crosstalk has been reported, microbiome-mediated effects on peripheral circadian clocks and their output genes are less well known. Here, we report that germ-free (GF) mice display altered daily oscillation of clock gene expression with a concomitant change in the expression of clock output regulators. Mice exposed to microbes typically exhibit characterized activities of nuclear receptors, some of which (PPARalpha, LXRbeta) regulate specific liver gene expression networks, but these activities are profoundly changed in GF mice. These alterations in microbiome sensitive gene expression patterns are associated with daily alterations in lipid, glucose, and xenobiotic metabolism, protein turnover, and redox balance, as revealed by hepatic metabolome analyses. Moreover, at the systemic level, daily changes in the abundance of biomarkers such as HDL cholesterol, free fatty acids, FGF21, bilirubin, and lactate depend on the microbiome. Altogether, our results indicate that the microbiome is required for integration of liver clock oscillations that tune output activators and their effectors, thereby regulating metabolic gene expression for optimal liver function. PMID- 26879575 TI - The importance of the lepidic component as a prognostic factor in stage I pulmonary adenocarcinoma. AB - BACKGROUND: Stage I pulmonary adenocarcinoma (PA) can offer an unfavorable prognosis. The aim of this study was to classify the prognosis of stage I PA on the basis of the lepidic component and to confirm whether the lepidic component can be used as a criterion for predicting the prognosis of stage I PA. METHODS: We conducted a retrospective study of patients who underwent curative surgery for stage I and IIA PA. Stage I disease was divided into three groups on the basis of the lepidic component: group 1, <=10%; group 2, >10 to 50%; and group 3, >50%. We compared recurrence-free survival (RFS) rates among groups 1, 2, and 3, and stage IIA disease. We also evaluated risk factors for disease recurrence with multivariate analysis. RESULTS: A total of 224 patients were included in our study; most patients (n=201) had stage I disease. Three-year RFS rates in group 1 (n=73), group 2 (n=75), and group 3 (n=53) were 74.1, 90.4, and 90.0%, respectively. There was a significant difference in RFS between group 1 and group 2 (p=0.009). The 3-year RFS rate in stage IIA disease was 61.4%. There were no significant differences in RFS between group 1 and stage IIA disease (p=0.163). In multivariate analysis, group 1 had the highest risk of recurrence (HR 5.806, p=0.006) in stage I PA. CONCLUSIONS: Stage I PA with a lepidic component<=10% was associated with an unfavorable prognosis that was similar to the prognosis of stage IIA disease. The prognosis for stage I PA should not be based on general criteria, but instead, the lepidic component should be evaluated and considered when determining disease prognosis. PMID- 26879576 TI - Left ventricular deformation associated with cardiomyocyte Ca(2+) transients delay in early stage of low-dose of STZ and high-fat diet induced type 2 diabetic rats. AB - BACKGROUND: In the early stage of diabetes, the cardiac ejection fraction is preserved, despite the existence of the subclinical cardiac dysfunction to some extent. However, the detailed phenotype of this dysfunction and the underlying mechanism remain unclear. To improve our understanding of this issue, we used low dose STZ and high-fat diet to induce type 2 diabetic models in rats. The effects and the mechanism associated with the early stages of the disease were analyzed. METHODS: The type 2 diabetic mellitus (T2DM) in SD rats were induced through 30 mg/kg STZ and high-fat diet. Two-dimensional spackle-tracking echocardiography (STE) and the dobutamine test were performed to examine the cardiac function. Calcium transients of left ventricular myocytes were detected and the related intracellular signalling factors were analyzed by western blotting. RESULTS: After 6-weeks, T2DM rats in left ventricular (LV) diastole showed decreased global and segment strain(S) levels (P < 0.05), both in the radial and circumferential directions. Strain rate (Sr) abatement occurred in three segments in the radial and circumferential directions (P < 0.05), and the radial global Sr also decreased (P < 0.05). In the systolic LV, radial Sr was reduced, except the segment of the anterior septum, and the Sr of the lateral wall and post septum decreased in the circumferential direction (P < 0.05). Conventional M-mode echocardiography failed to detect significant alterations of cardiac performance between the two groups even after 12 weeks, and the decreased ejection fraction (EF%), fractional shortening (FS%) and end-systolic diameters (ESD) could be detected only under stress conditions induced by dobutamine (P < 0.05). In terms of calcium transients in cardiac myocytes, the Tpeak in model rats at 6 weeks was not affected, while the Tdecay1/2 was higher than that of the controls (P < 0.05), and both showed a dose-dependent delay after isoproterenol treatment (P < 0.05). Western blot analysis showed that in 6-week T2DM rats, myocardial p-PLB expression was elevated, whereas p-CaMKII, p-AMPK and Sirt1 were significantly down-regulated (P < 0.05). CONCLUSION: A rat model of T2DM was established by low dose STZ and a high-fat diet. LV deformation was observed in the early stages of T2DM in association with the delay of Ca(2+) transients in cardiomyocytes due to the decreased phosphorylation of CaMKII. Myocardial metabolism remodeling might contribute to the early LV function and calcium transportation abnormalities. PMID- 26879578 TI - Bilateral facial palsy in a child. PMID- 26879579 TI - Validation of the French-language version of the OTOSPEECH automated scoring software package for speech audiometry. AB - OBJECTIVES: To validate a novel speech audiometry method using customized self voice recorded word lists with automated scoring. PATIENTS AND METHODS: The self voice effect was investigated by comparing results with prerecorded or self recorded CVC (consonant-vowel-consonant) word lists. Then customized lists of 3 phoneme words were drawn up using the OTOSPEECH software package, and their scores were compared to those for reference lists. Finally, the customized list scores were compared on automated (Dynamic Time Warping [DTW]) versus manual scoring. RESULTS: Self-voice did not change scores for perception of CVC words at 10, 20 and 30 dB (ANOVA>0.05). Scores obtained with pre-recorded and self recorded lists correlated (n=10, R(2)=0.76, P<0.01). Customized list scores correlated strongly with the reference cochlear lists of Lafon in normal-hearing (n=77, R(2)=0.83, P<0.001) and hearing-impaired populations (n=13, R(2)=0.89, P<0.001). Results on the automated and manual scoring methods correlated in both populations (n=77, R(2)=0.71, P<0.01; and n=13, R(2)=0.76, P<0.01, respectively), with DTW scores ranging from 24.17 to 53.24. CONCLUSIONS: Automated scoring of customized self-voice recorded lists for speech audiometry displayed results similar to conventional audiometric techniques. PMID- 26879580 TI - Sternocleidomastoid pyomyositis. AB - INTRODUCTION: Pyogenic myositis (pyomyositis) represents a bacterial infection of striated muscle. Predominantly associated with tropical regions and commonly caused by Staphylococcus aureus, the incidence of cervical pyomyositis is rare. To our knowledge, we report the first case of group A streptococcal cervical pyomyositis in an immunocompetent British Caucasian patient. CASE PRESENTATION: A previously well 48-year-old Caucasian male presented with sore throat, left sided neck pain and swelling. He was a lifelong non-smoker with no recent travel or animal exposure. On admission, he was febrile with unilateral neck swelling. Random blood glucose was normal and an HIV test negative. CT imaging confirmed a large heterogeneous mass extending throughout the entirety of the left sternocleidomastoid muscle. The patient underwent exploration and drainage of a large intra-sternocleidomastoid neck abscess. Microbiology identified group A - streptococcus. Histology confirmed abscess formation in muscle with no acid-fast bacilli. The patient recovered well postoperatively and continues to do well. DISCUSSION: Cervical pyomyositis is a rare condition that if not treated appropriately may cause internal jugular vein thrombosis, sepsis and death. Pyomyositis requires a high index of suspicion and should be considered a differential diagnosis in any painful swelling in the head and neck region. PMID- 26879577 TI - Evidence of TAF1 dysfunction in peripheral models of X-linked dystonia parkinsonism. AB - The molecular dysfunction in X-linked dystonia-parkinsonism is not completely understood. Thus far, only noncoding alterations have been found in genetic analyses, located in or nearby the TATA-box binding protein-associated factor 1 (TAF1) gene. Given that this gene is ubiquitously expressed and is a critical component of the cellular transcription machinery, we sought to study differential gene expression in peripheral models by performing microarray-based expression profiling in blood and fibroblasts, and comparing gene expression in affected individuals vs. ethnically matched controls. Validation was performed via quantitative polymerase chain reaction in discovery and independent replication sets. We observed consistent downregulation of common TAF1 transcripts in samples from affected individuals in gene-level and high throughput experiments. This signal was accompanied by a downstream effect in the microarray, reflected by the dysregulation of 307 genes in the disease group. Gene Ontology and network analyses revealed enrichment of genes involved in RNA polymerase II-dependent transcription, a pathway relevant to TAF1 function. Thus, the results converge on TAF1 dysfunction in peripheral models of X-linked dystonia-parkinsonism, and provide evidence of altered expression of a canonical gene in this disease. Furthermore, our study illustrates a link between the previously described genetic alterations and TAF1 dysfunction at the transcriptome level. PMID- 26879581 TI - Analysis of case reports submitted to the European Annals of Otorhinolaryngology Head & Neck Diseases. AB - OBJECTIVES: To assess flaws, rejection rate and reasons for rejection of case reports submitted for publication in the European Annals of Otorhinolaryngology Head & Neck Diseases. MATERIALS AND METHODS: A prospective analysis of flaws noted in reviewing 118 case reports from 29 countries consecutively submitted to the European Annals of Otorhinolaryngology Head & Neck Diseases during the period Sept. 1, 2014 to Sept. 30, 2015. RESULTS: The most frequent flaws, noted in 74.5% of cases, were: lack of originality (more than 15 such cases previously reported in the medical literature) and lack of new data contributing to the medical literature. Overall, 5% of the cases were accepted for publication, 7% were not resubmitted by the authors, and 88% were rejected. On univariate analysis, none of the variables under analysis correlated with acceptance or rejection of the submitted case. Editorial decision time varied from 1 to 7months (median, 1 month). In 16.3% of the 104 cases of rejection (17/104), the editors suggested resubmission in the section "Letter to the Editor" or "What is your diagnosis?"; 15 of the 17 reports were resubmitted, and 10 (66.6%) were ultimately accepted for publication. CONCLUSION: The editorial committee of the European Annals of Otorhinolaryngology Head & Neck Diseases hope that the present data and review of the literature will provide authors with a framework to avoid major errors leading to rejection and will speed publication of the case reports they submit to our columns in the near future. PMID- 26879582 TI - SpxB-mediated H2 O2 induces programmed cell death in Streptococcus sanguinis. AB - Streptococcus sanguinis (S. sanguinis) is a commensal oral streptococci that produces hydrogen peroxide (H2 O2 ), and this production is dependent on pyruvate oxidase (SpxB) activity. In addition to its well-known role in intraspecies or interspecies competitions, recent studies have shown that H2 O2 produced by S. sanguinis under aerobic conditions not only upregulates biofilm formation and eDNA release but also regulates cell death without obvious cell lysis. Here, we report that S. sanguinis exhibits characteristic hallmarks of eukaryotic apoptosis when it encounters endogenous and exogenous H2 O2 . As the most common mode of programmed cell death (PCD), apoptosis is accompanied by a series of biochemical and morphological events, including DNA fragmentation, chromosome condensation, membrane potential depolarization, phosphatidylserine (PS) exposure, and caspase substrate binding protein activity changes. In addition, we also provide genetic evidence that there is decreased expression of the related DNA repair genes comEA, recA, dnaC, dinG, and pcrA in the wild-type compared to the isogenic spxB mutant in S. sanguinis. Our data suggest that endogenous H2 O2 is the most important agent in this development process in S. sanguinis. PMID- 26879583 TI - Inducing femoral vein thrombosis under unrestricted flow: Comments on an alternative electrolytic mouse model. PMID- 26879584 TI - Influence of harvest season on chemical composition and bioactivity of wild rue plant hydroalcoholic extracts. AB - The rue (Ruta graveolens) copiousness in rural areas of the Campania Region based a thorough chemical and biological investigation aimed at exploring the seasonal variability of phenol constituents in rue leaves and its influence on their antioxidant, cytotoxic and anti-inflammatory capabilities. To this purpose, hydroalcoholic extracts were prepared from plant samples seasonally collected. LC ESI-MS/MS techniques were employed to analyze qualitatively and quantitatively the seasonal rue phenol content, whereas different chemical antioxidant assays (by DPPH, ABTS, Fe(3+) RP, ORAC, and FCR methods) and XTT redox metabolic activity assay were performed to screen the seasonal phenol complex-related antioxidant and cytotoxic power. The ability of the rue leaf extracts to counteract cyclooxygenase-2 (COX-2) expression was also evaluated. Data obtained highlighted that the adopted extraction procedure markedly pauperized the furanocoumarin content in all the prepared rue extracts. Flavonol glycosides, along with the flavone acacetin and two sinapic acid derivatives were the main constituents of the spring harvest-derived extract, which exerted the highest antioxidant capability in cell-free systems and was capable to inhibit COX-2 synthesis by 44% comparably to dexamethasone, used as positive control. Data provide new insights for developing a proper management of rue plants for new safe industrial purposes in herbal medicine field. PMID- 26879585 TI - The influence of Mg2+ coordination on 13C and 15N chemical shifts in CKI1RD protein domain from experiment and molecular dynamics/density functional theory calculations. AB - Sequence dependence of (13) C and (15) N chemical shifts in the receiver domain of CKI1 protein from Arabidopsis thaliana, CKI1RD , and its complexed form, CKI1RD *Mg(2+), was studied by means of MD/DFT calculations. MD simulations of a 20-ns production run length were performed. Nine explicitly hydrated structures of increasing complexity were explored, up to a 40-amino-acid structure. The size of the model necessary depended on the type of nucleus, the type of amino acid and its sequence neighbors, other spatially close amino acids, and the orientation of amino acid NH groups and their surface/interior position. Using models covering a 10 and a 15 A environment of Mg(2+), a semi-quantitative agreement has been obtained between experiment and theory for the V67-I73 sequence. The influence of Mg(2+) binding was described better by the 15 A as compared to the 10 A model. Thirteen chemical shifts were analyzed in terms of the effect of Mg(2+) insertion and geometry preparation. The effect of geometry was significant and opposite in sign to the effect of Mg(2+) binding. The strongest individual effects were found for (15) N of D70, S74, and V68, where the electrostatics dominated; for (13) Cbeta of D69 and (15) N of K76, where the influences were equal, and for (13) Calpha of F72 and (13) Cbeta of K76, where the geometry adjustment dominated. A partial correlation between dominant geometry influence and torsion angle shifts upon the coordination has been observed. PMID- 26879586 TI - Childhood adversity and conduct disorder: A developmental pathway to violence in schizophrenia. AB - BACKGROUND: Both childhood adversity and conduct disorder are over-represented among adult patients with schizophrenia and have been proposed as significant factors that may increase the risk of violence. It is not known how childhood adversity and conduct disorder might interact to contribute towards an increased risk of violence in schizophrenia. This study aimed to explore the relationships between childhood adversity, conduct disorder and violence among men with schizophrenia. METHODS: 54 male patients with schizophrenia from a range of inpatient and outpatient mental health services were assessed for exposure to a variety of childhood adversities, conduct disorder before the age of 15 and later violent behaviour in adulthood. RESULTS: Exposure to domestic violence during childhood was associated with an increased propensity to violence in adulthood. Symptoms of conduct disorder were associated both with cumulative exposure to childhood adversities and with later propensity to violence. The cumulative number of childhood adversities was associated with adult propensity to violence. This association was significantly attenuated by inclusion of conduct disorder in the model. CONCLUSIONS: This is the first study to demonstrate an association between childhood exposure to domestic violence and later violent behaviour in schizophrenia. Conduct disorder may mediate the association between cumulative childhood adversities and adult propensity to violence, indicating an indirect pathway. These results indicate a complex interplay between childhood adversity, conduct disorder and later violent behaviour in schizophrenia, and suggest that there may be shared aetiological risk factors on a common developmental pathway to violence. PMID- 26879588 TI - The relationship between paranoia and aggression in psychosis: A systematic review. AB - Aggression in the context of schizophrenia has significant detrimental personal, clinical and societal implications. Whilst understanding the precise pathways to aggression in people with a diagnosis of schizophrenia is critical for risk management and treatment, these pathways remain unclear. A paranoid belief that others intend harm is one psychotic symptom that might contribute to aggressive behaviours. This is the first review to investigate the relationship between paranoia and aggression in psychosis. A systematic review of published literature pertinent to the relationship between paranoia and aggression was conducted. A search of online databases from inception to November 2014 was performed with keywords related to 'schizophrenia', 'paranoia' and 'aggression'. Fifteen studies, primarily cross-sectional in design (n=9), met eligibility criteria. Studies reviewed showed mixed support for an association between paranoia and aggression in both inpatients and community settings. However, when study quality was taken into account, more methodologically rigorous studies tended to show a positive association between factors. Mixed findings are most likely due to important methodological shortcomings, including heterogeneous samples and studies using a diverse range of aggression/violence measures. In light of methodological limitations of individual studies reviewed, further investigation of the relationship between paranoia and aggression in psychosis using robust methodology is needed before definitive clinical recommendations regarding the hypothesised relationship between paranoia and aggression can be made. This paper sets out key recommendations for future studies, including operationalizing the specific components of aggression and paranoia under investigation and methods to delineate important mediators in the paranoia and aggression relationship. PMID- 26879587 TI - Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia. AB - Several clinical studies have found an inverse relationship between clinical symptoms and peripheral oxytocin (OT) levels in people with schizophrenia. As oxytocin is a putative treatment for schizophrenia, the effect of repeated dosing of OT on OT levels, clinical symptoms and the relationship between the two is of interest. In a, randomized, double blind, parallel group 3 week study (N=28) with daily administration of intranasal OT (20 IU twice daily) or placebo (PBO), we examined the effect of OT administration on the correlation between the change in peripheral OT levels and change in clinical symptoms in patients with schizophrenia. At baseline, there were no significant treatment group differences in OT levels. There were no significant associations between baseline OT levels and any symptom measures. After 3 weeks of OT/PBO dosing, there was no significant difference in the magnitude of change in OT levels between the two treatment groups. Correlations between changes in peripheral OT levels and changes in the BPRS total and negative symptom scores were not different between treatment groups. Larger studies are needed to examine the effect of exogenous OT on peripheral OT levels and the relationship between the latter and clinical symptoms. Clinical Trials.gov=NCT00884897. PMID- 26879589 TI - Early relapse of severe chronic active Epstein-Barr virus infection with posterior reversible encephalopathy syndrome after reduced intensity stem cell transplantation with umbilical cord blood. PMID- 26879591 TI - A gold nanoparticle-based semi-quantitative and quantitative ultrasensitive paper sensor for the detection of twenty mycotoxins. AB - A semi-quantitative and quantitative multi-immunochromatographic (ICA) strip detection assay was developed for the simultaneous detection of twenty types of mycotoxins from five classes, including zearalenones (ZEAs), deoxynivalenols (DONs), T-2 toxins (T-2s), aflatoxins (AFs), and fumonisins (FBs), in cereal food samples. Sensitive and specific monoclonal antibodies were selected for this assay. The semi-quantitative results were obtained within 20 min by the naked eye, with visual limits of detection for ZEAs, DONs, T-2s, AFs and FBs of 0.1 0.5, 2.5-250, 0.5-1, 0.25-1 and 2.5-10 MUg kg(-1), and cut-off values of 0.25-1, 5-500, 1-10, 0.5-2.5 and 5-25 MUg kg(-1), respectively. The quantitative results were obtained using a hand-held strip scan reader, with the calculated limits of detection for ZEAs, DONs, T-2s, AFs and FBs of 0.04-0.17, 0.06-49, 0.15-0.22, 0.056-0.49 and 0.53-1.05 MUg kg(-1), respectively. The analytical results of spiked samples were in accordance with the accurate content in the simultaneous detection analysis. This newly developed ICA strip assay is suitable for the on site detection and rapid initial screening of mycotoxins in cereal samples, facilitating both semi-quantitative and quantitative determination. PMID- 26879592 TI - Pharmacologic treatment for postviral olfactory dysfunction: a systematic review. AB - BACKGROUND: Postviral olfactory dysfunction (PVOD) is the most common cause of olfactory dysfunction. Several treatments have been presented in the literature. The objective of this study is to systematically review the existing literature on the effectiveness of pharmacologic treatments for PVOD. METHODS: We performed a literature search of PubMed, Ovid, and ScienceDirect from 1966 to 2014. Inclusion criteria included English-language articles containing original data on pharmacologic treatment of PVOD with >=5 subjects, measurable outcomes, and readily available treatments. Data was collected regarding study design, subject demographic information, clinical outcomes, and level of evidence. Two investigators reviewed all articles independently. RESULTS: Of 445 abstracts identified, 8 articles were included, yielding 563 patients. Treatments investigated included oral corticosteroids, local injections of corticosteroids, zinc sulfate, alpha lipoic acid, caroverine, vitamin A, Ginkgo biloba, and minocycline. Outcome measures were determined by symptom scores and objective olfactory test methods-the most common being Sniffin' Sticks. Improvement was noted in subjects receiving oral corticosteroid therapy, local injections of corticosteroid, alpha lipoic acid, and caroverine, whereas vitamin A, zinc sulfate, Ginkgo biloba, and minocycline groups did not show significant improvement. CONCLUSION: The majority of therapies investigated that show benefit in treating PVOD are of poor quality. Although caroverine therapy showed benefit and is a level 1b study, etiologies of olfactory dysfunction other than PVOD were included as well, which clouds the results. Overall, there is no strong evidence for any pharmacologic treatment of PVOD in the literature. PMID- 26879590 TI - Combatting Synthetic Designer Opioids: A Conjugate Vaccine Ablates Lethal Doses of Fentanyl Class Drugs. AB - Fentanyl is an addictive prescription opioid that is over 80 times more potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous "designer drug" analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross-reactivity for a wide panel of fentanyl analogues. Moreover, vaccinated mice gained significant protection from lethal fentanyl doses. Lastly, a surface plasmon resonance (SPR)-based technique was established enabling drug-specificity profiling of antibodies derived directly from serum. Our newly developed fentanyl vaccine and analytical methods may assist in the battle against synthetic opioid abuse. PMID- 26879593 TI - Quantitative Imaging of FRET-Based Biosensors for Cell- and Organelle-Specific Analyses in Plants. AB - Genetically encoded Forster resonance energy transfer (FRET)-based biosensors have been used to report relative concentrations of ions and small molecules, as well as changes in protein conformation, posttranslational modifications, and protein-protein interactions. Changes in FRET are typically quantified through ratiometric analysis of fluorescence intensities. Here we describe methods to evaluate ratiometric imaging data acquired through confocal microscopy of a FRET based inorganic phosphate biosensor in different cells and subcellular compartments of Arabidopsis thaliana. Linear regression was applied to donor, acceptor, and FRET-derived acceptor fluorescence intensities obtained from images of multiple plants to estimate FRET ratios and associated location-specific spectral correction factors with high precision. FRET/donor ratios provided a combination of high dynamic range and precision for this biosensor when applied to the cytosol of both root and leaf cells, but lower precision when this ratiometric method was applied to chloroplasts. We attribute this effect to quenching of donor fluorescence because high precision was achieved with FRET/acceptor ratios and thus is the preferred ratiometric method for this organelle. A ligand-insensitive biosensor was also used to distinguish nonspecific changes in FRET ratios. These studies provide a useful guide for conducting quantitative ratiometric studies in live plants that is applicable to any FRET-based biosensor. PMID- 26879594 TI - Population pharmacokinetic analysis of lenvatinib in healthy subjects and patients with cancer. AB - AIMS: Lenvatinib was recently approved for the treatment of radioiodine refractory differentiated thyroid cancer (RR-DTC). Here, we characterized the pharmacokinetic (PK) profile of lenvatinib and identified intrinsic and extrinsic factors that explain interindividual PK variability in humans. METHODS: This population PK analysis used pooled data from 15 clinical studies, including eight phase 1 studies in healthy subjects, four phase 1 studies in patients with solid tumours, two phase 2 studies in patients with thyroid cancer and one phase 3 study in patients with RR-DTC. RESULTS: The final pooled dataset included data from 779 subjects receiving 3.2-32 mg oral lenvatinib, mainly once daily as tablets or capsules. Lenvatinib PK was best described by a three-compartment model with linear elimination. Lenvatinib absorption was best described by simultaneous first- and zero-order absorption. The population mean value for lenvatinib apparent clearance (CL/F) was 6.56 l h(-1) [percent coefficient of variation (%CV) 25.5], and was independent of dose and time. The relative bioavailability of lenvatinib in capsule form was 90% vs. tablets (%CV 30.2). The final PK model included significant but marginal effects of body weight (2.8% of CL/F variation), liver-function markers [alkaline phosphatase (-11.7%) and albumin (-6.3%)] and concomitant cytochrome P450 3A4 inducers (+30%) and inhibitors (-7.8%) on lenvatinib CL/F. Lenvatinib PK was unaffected by pH elevating agents, dose, age, sex, race, alanine aminotransferase, aspartate aminotransferase or bilirubin levels, or renal function. CONCLUSIONS: The significant effects of several covariates on lenvatinib PK variability were small in magnitude, and therefore were not considered clinically relevant, or to warrant any dose adjustment. PMID- 26879595 TI - Multisite musculoskeletal pain among young technical school students entering working life. AB - BACKGROUND: There is a need to investigate the occurrence of multisite pain in young adults and to determine potential factors contributing to the early course of multisite musculoskeletal pain. The aim of this prospective study was to assess the occurrence and change of prevalence in the number of pain sites. We also wanted to identify work-related and individual risk factors associated with the number of musculoskeletal pain sites. METHODS: We monitored musculoskeletal pain from 4 body regions, individual and work-related factors on 21 occasions over a 6.5 year period. The cohort consisted of 420 technical school students entering working life. Data were analyzed by generalized estimating equations (GEE). RESULTS: Pain from more than one body site was prevalent in this cohort of young adults (69 % at baseline), and the number of body sites in pain was found quite stable over the 6.5 year follow-up period. Women had higher number of pain sites compared with men and gender specific risk factors were identified. Increased mechanical workload and quantitative demands and low socioeconomic status were associated with increased number of musculoskeletal pain sites among women, while tobacco use was found as a risk factor among young men. Increased perceived muscle tension was the only factor significantly associated with increased number of pain sites in both genders. CONCLUSION: The current study supports earlier findings and show that pain from multiple body sites are frequent also among young workers. The identification of gender specific risk factors in our study is important and may facilitate practical prevention and future research. PMID- 26879596 TI - Formation of a highly-ordered rigid multichromophoric 3D supramolecular network by combining ionic and coordination-driven self-assembly. AB - We present here the self-assembly of a green-emitting metallosupramolecular rhomboid into a rigid, highly-ordered 3D multichromophoric network through the mediation of a tetra-anionic violet-blue molecular emitter. Control was obtained on the spatial topology, the electronic energy landscape and the fluorescence polarization of the interacting dipoles. PMID- 26879597 TI - A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis. AB - OBJECTIVE: To determine the utility of a prehospital sepsis screening protocol utilizing systemic inflammatory response syndrome (SIRS) criteria and end-tidal carbon dioxide (ETCO2). METHODS: We conducted a prospective cohort study among sepsis alerts activated by emergency medical services during a 12 month period after the initiation of a new sepsis screening protocol utilizing >=2 SIRS criteria and ETCO2 levels of <=25 mmHg in patients with suspected infection. The outcomes of those that met all criteria of the protocol were compared to those that did not. The main outcome was the diagnosis of sepsis and severe sepsis. Secondary outcomes included mortality and in-hospital lactate levels. RESULTS: Of 330 sepsis alerts activated, 183 met all protocol criteria and 147 did not. Sepsis alerts that followed the protocol were more frequently diagnosed with sepsis (78% vs 43%, P < .001) and severe sepsis (47% vs 7%, P < .001), and had a higher mortality (11% vs 5%, P = .036). Low ETCO2 levels were the strongest predictor of sepsis (area under the ROC curve (AUC) of 0.99, 95% CI 0.99-1.00; P < .001), severe sepsis (AUC 0.80, 95% CI 0.73-0.86; P < .001), and mortality (AUC 0.70, 95% CI 0.57-0.83; P = .005) among all prehospital variables. Sepsis alerts that followed the protocol had a sensitivity of 90% (95% CI 81-95%), a specificity of 58% (95% CI 52-65%), and a negative predictive value of 93% (95% CI 87-97%) for severe sepsis. There were significant associations between prehospital ETCO2 and serum bicarbonate levels (r = 0.415, P < .001), anion gap (r = -0.322, P < .001), and lactate (r = -0.394, P < .001). CONCLUSION: A prehospital screening protocol utilizing SIRS criteria and ETCO2 predicts sepsis and severe sepsis, which could potentially decrease time to therapeutic intervention. PMID- 26879598 TI - [Assessment method for mobile health applications in Spanish: The iSYScore index]. AB - The widespread of mobile smartphones among the population has resulted in a growing range of mobile applications in health using iOS and Android devices. The level of confidence that such applications deserve and the health information available online to the general population is a widely debated issue. The main objective of this work was to develop a tool -a scale-, for evaluating the reliability of health apps. The scale was developed using a systematic evidence based approach, and with an expert consensus, built with a Delphi process. This was followed by a health app catalogue, which was used to test and validate our method that helps to recommend the best apps for non-medical experts across 3 different user interest axes: 1) popularity and interest; 2) trust and quality; and 3) usefulness. PMID- 26879599 TI - Corrigendum. PMID- 26879602 TI - Molecular Design and Syntheses of Tetracyano-5,10-porphyrinquinodimethane Showing Stabilized LUMO. AB - An isomer of tetracyanoporphyrinquinodimethane (TCPQ), 5,10-TCPQ, was designed, synthesized, and structurally characterized, and its basic properties were discussed with emphasis on comparison with those of reported 5,15-TCPQ. The title compound was synthesized by a convenient cascade reaction involving a catalyst free aromatic nucleophilic substitution reaction and the Uno-Takahashi reaction. The obtained pi-expanded redox molecule acted as a Wurster-type redox molecule that underwent not only reduction but also oxidation processes. Furthermore, its absorption spectrum showed a large bathochromic shift that extended to the near IR region, approximately 1150 nm. PMID- 26879601 TI - BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma. AB - BACKGROUND: The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. METHODS: Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. RESULTS: Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. CONCLUSIONS: BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC. PMID- 26879604 TI - Halide-Free Synthesis of Hydrochalcogenide Ionic Liquids of the Type [Cation][HE] (E=S, Se, Te). AB - We present the synthesis and thorough characterization of ionic liquids and organic salts based on hydrochalcogenide HE(-) (E=S, Se, Te) anions. Our approach is based on halide-, metal-, and water-free decarboxylation of methylcarbonate precursors under acidic conditions, resulting from the easily dissociating reagents H2 E. The compounds were characterized by elemental analysis, multinuclear NMR spectroscopy, thermal and single-crystal XRD analyses. The hydrosulfide salts were investigated with respect to their ability to dissolve elemental sulfur in varying stoichiometry. Thus-prepared polysulfide ILs were also analyzed by UV/Vis spectroscopy and cyclic voltammetry. PMID- 26879603 TI - Serum microRNA microarray analysis identifies miR-4429 and miR-4689 are potential diagnostic biomarkers for biliary atresia. AB - This study aimed to investigate pathogenesis and novel diagnostic biomarkers of biliary atresia (BA). Serum samples from infants with BA and non-BA neonatal cholestasis (NC) were collected for miRNA microarray analysis, and then differentially expressed miRNAs were screened. Differentially expressed miRNAs were validated by qRT-PCR using an independent serum samples from infants with BA and NC. Diagnostic utility of validated miRNAs was further analyzed using serum samples by receiver-operating characteristic curve analysis. Totally, 13 differentially expressed miRNAs were identified including 11 down-regulated and 2 up-regulated ones. Target genes of hsa-miR-4429 and hsa-miR-4689 were significantly involved in FoxO signaling pathway. Eight differentially expressed miRNAs were chosen for validation by qRT-PCR analysis, and four miRNAs (hsa-miR 150-3p, hsa-miR-4429, hsa-miR-4689 and hsa-miR-92a-3p) were differentially expressed. The area under the curve of hsa-miR-4429 and hsa-miR-4689 was 0.789 (sensitivity = 83.33%, specificity = 80.00%) and 0.722 (sensitivity = 66.67%, specificity = 80.00%), respectively. Differentially expressed miRNAs including hsa-miR-4429 and hsa-miR-4689 might play critical roles in BA by regulating their target genes, and these two miRNAs may have the potential to become diagnostic biomarkers. PMID- 26879600 TI - Could gestational diabetes mellitus be managed through dietary bioactive compounds? Current knowledge and future perspectives. AB - Gestational diabetes mellitus (GDM) is a serious problem growing worldwide that needs to be addressed with urgency in consideration of the resulting severe complications for both mother and fetus. Growing evidence indicates that a healthy diet rich in fruit, vegetables, nuts, extra-virgin olive oil and fish has beneficial effects in both the prevention and management of several human diseases and metabolic disorders. In this review, we discuss the latest data concerning the effects of dietary bioactive compounds such as polyphenols and PUFA on the molecular mechanisms regulating glucose homoeostasis. Several studies, mostly based on in vitro and animal models, indicate that dietary polyphenols, mainly flavonoids, positively modulate the insulin signalling pathway by attenuating hyperglycaemia and insulin resistance, reducing inflammatory adipokines, and modifying microRNA (miRNA) profiles. Very few data about the influence of dietary exposure on GDM outcomes are available, although this approach deserves careful consideration. Further investigation, which includes exploring the 'omics' world, is needed to better understand the complex interaction between dietary compounds and GDM. PMID- 26879606 TI - Boron(III)-Containing Donor-Acceptor Compound with Goldlike Reflective Behavior for Organic Resistive Memory Devices. AB - A small-molecule-based boron(III)-containing donor-acceptor compound has been designed and synthesized. Interesting goldlike reflective behavior was observed in the neat thin-film sample from simple spin-coating preparation, which can serve as a potential organic thin-film optical reflector. The small thickness in nanometer range and the relatively smooth surface morphology, together with simple preparation and easy solution processability, are attractive features for opening up new avenues for the fabrication of reflective coatings. Moreover, this donor-acceptor compound has been employed in the fabrication of organic resistive memory device, which exhibited good performance with low turn-on voltage, small operating bias, large ON/OFF ratio, and long retention time. PMID- 26879605 TI - Size-Dependent Electrocatalytic Activity of Free Gold Nanoparticles for the Glucose Oxidation Reaction. AB - Understanding the fundamental relationship between the size and the structure of electrode materials is essential to design catalysts and enhance their activity. Therefore, spherical gold nanoparticles (GNSs) with a mean diameter from 4 to 15 nm were synthesized. UV/Vis spectroscopy, transmission electron microscopy, and under-potential deposition of lead (UPDPb ) were used to determine the morphology, size, and surface crystallographic structure of the GNSs. The UPDPb revealed that their crystallographic facets are affected by their size and the growth process. The catalytic properties of these GNSs toward glucose electrooxidation were studied by cyclic voltammetry, taking into account the scan rate and temperature effects. The results clearly show the size-dependent electrocatalytic activity for glucose oxidation reactions that are controlled by diffusion. Small GNSs with an average size of 4.2 nm exhibited high catalytic activity. This drastic increase in activity results from the high specific area and reactivity of the surface electrons induced by their small size. The reaction mechanism was investigated by in situ Fourier transform infrared reflectance spectroscopy. Gluconolactone and gluconate were identified as the intermediate and the final reaction product, respectively, of the glucose electrooxidation. PMID- 26879607 TI - Conformational switch-mediated accelerated release of drug from cytosine-rich nucleic acid-capped magnetic nanovehicles. AB - A novel concept that the conformational switch of cytosine-rich DNA can accelerate the release of drug from DNA-capped nanovehicles is rationally devised. Our present strategy can greatly extend the potential usages of DNA molecules with specific sequences as conformational switch-controlled devices. PMID- 26879608 TI - Patterned Thermoresponsive Microgel Coatings for Noninvasive Processing of Adherent Cells. AB - Cultivation of adherently growing cells in artificial environments is of utmost importance in medicine and biotechnology to accomplish in vitro drug screening or to investigate disease mechanisms. Precise cell manipulation, like localized control over adhesion, is required to expand cells, to establish cell models for novel therapies and to perform noninvasive cell experiments. To this end, we developed a method of gentle, local lift-off of mammalian cells using polymer surfaces, which are reversibly and repeatedly switchable between a cell attractive and a cell-repellent state. This property was introduced through micropatterned thermoresponsive polymer coatings formed from colloidal microgels. Patterning was obtained through automated nanodispensing or microcontact printing, making use of unspecific electrostatic interactions between microgels and substrates. This process is much more robust against ambient conditions than covalent coupling, thus lending itself to up-scaling. As an example, wound healing assays were accomplished at 37 degrees C with highly increased precision in microfluidic environments. PMID- 26879609 TI - [Repeated partially reversible pulmonary arterial hypertension related to dasatinib: a case report and literature review]. AB - OBJECTIVE: To study the clinical features and prognosis of pulmonary arterial hypertension related to dasatinib. METHODS: A case of pulmonary arterial hypertension(PAH) during dasatinib therapy was retrospectively analyzed and the related literature was reviewed. RESULTS: A 55-year-old male with chronic myelogenous leukemia was treated with dasatinib at a dosage of 100 mg/d.After 36 months of initiating the therapy, he presented with chest distress, fatigue and general edema. His heart function was graded as NHYA IV. Transthoracic Doppler echocardiography documented right ventricle enlargement, right ventricular wall thickening, reduction of right ventricular systolic function, widening of the main pulmonary artery and branches , and an estimated systolic pulmonary arterial pressure(SPAP) of 115 mmHg(1 mmHg=0.133 kPa), with pericardial effusion and normal systolic left ventricular function.Chest ultrasound documented bilateral pleural effusion.The patient had taken and withdrew dasatinib 5 times by himself.The symptom had improved after stopping the drug, with SPAP decreasing to 37-82 mmHg measured by echocardiography at the first 3 times, and the pleural effusion and the pericardial effusion had disappeared. But 1 year after the 4(th) withdrawal of the drug, his pulmonary arterial pressure had failed to decrease, and he had taken the drug again by himself. Other causes of pulmonary arterial hypertension such as lung parenchymal diseases, pulmonary thromboembolism, connective tissue diseases, other drug induced PAH, were excluded by extensive examinations. The patient refused to receive right-sided heart catheterization. The patient was followed until now. CONCLUSIONS: Dasatinib can cause partially reversible PAH. But after repeated use of the drug, PAH may become irreversible. Monitoring SPAP by transthoracic Doppler echocardiography is necessary during dasatinib therapy. PMID- 26879610 TI - [The clinical features of primary or metastatic malignancies presenting with multiple lung cavities]. AB - OBJECTIVE: To evaluate the clinical, radiological and pathological features of primary or metastatic malignancies presenting with multiple lung cavities. METHODS: A total of 38 cases met the inclusion criteria and had adequate imaging data for retrospective review between June 2006 and August 2013. There were 30 cases of primary lung cancer, and 8 cases of pulmonary metastasis including 6 gastrointestinal tract malignancies, 1 vulva malignancy and 1 scalp malignancy. There were 21 females and 17 males, with a median age of 63 years. RESULTS: Cough and expectoration were the most common clinical manifestations of primary lung cancer(22/30). There were 4 main types of lung cavities, including thick-walled cavities(n=12), circular cavities (n=24), thin-walled cavities or cystic cavities (n=11), cavities or multi-cystic changes within airspace consolidation or ground glass opacity(n=11). The cavitary lesions were often accompanied by pulmonary nodules, mass and ground glass opacity(32/38, 84%). The presence of internal soft tissue septa in the cavity was commonly seen(17/38, 45%). The 4(th) type of cavity and presence of air-fluid levels were only found in lung adenocarcinoma, including 5 cases of mucinous adenocarcinoma. In both primary lung cancers and metastatic tumors, adenocarcinoma was the most common histological type (29/30 and 6/8, respectively). The other histological types included 1 case of lung squamous cell carcinoma, 1 vulva adenosquamous carcinoma and 1 scalp angiosarcoma. The possible mechanisms of cavity formation included necrosis, mucin-secretion air-containing cystic spaces in papillary tumors and the check valve mechanism. CONCLUSIONS: Adenocarcinoma was the most common histological type in multiple cavitary primary lung cancers and metastatic tumors. These cavities showed varied radiological features and were easy to be misdiagnosed as benign cavitary lung diseases. PMID- 26879611 TI - [The expression and clinical role of KL-6 in serum and BALF of patients with different diffuse interstitial lung diseases]. AB - OBJECTIVE: To detect the levels of KL-6 in the serum and the bronchoalveolar lavage fluid (BALF) of patients with different type of diffuse interstitial lung diseases(DILD), and to analyze its correlation with pulmonary function, pulmonary HRCT scores and other parameters. METHOD: Seventy-three patients with DILD were enrolled, including 34 patients with idiopathic pulmonary fibrosis (IPF), 10 patients with stage I sarcoidosis(SAR I), 15 patients with hypersensitivity pneumonia (HP), 14 patients with connective tissue diseases (CTD). Enzyme-linked immune sorbent assay (ELISA) was used to detect the levels of KL-6 in the serum and the BALF of these patients. RESULTS: In the IPF group, FVC predicted percentage and DLCO predicted percentage were significantly lower than those of the SAR I group[(70+/-14)% vs (82+/-6)%, (49+/-13)% vs(81+/-6)%, P<0.05], but were no different compared to the CTD-ILD group(P>0.05). In the IPF group, the percentage of neutrophils in BALF was higher than that of the SAR I group[(9+/ 7)% vs (6+/-4)%, P<0.05]], and the percentage of lymphocytes and CD4/CD8 ratio in BALF were lower than those of the SAR I group[(12+/-7)% vs (23+/-13)%, (1.5+/ 0.8) vs(4.0+/-5.1), P<0.05]. In the IPF group, the level of KL-6 in serum was higher than that of the SAR I and the HP group[(858+/-516)U/ml vs (339+/ 168)U/ml, (553+/-287)U/ml, P<0.05], but was no different compared to the CTD-ILD group (P>0.05). In the CTD-ILD group, the level of KL-6 in serum was higher than that of the SAR I [(687+/-350) U/ml vs (339+/-168)U/ml, P<0.05]]. In the IPF group, the level of KL-6 in BALF was (437+/-252)U/ml, and was higher than that of other 3 groups(P<0.05). In the IPF group, the level of serum KL-6 was negatively correlated with FVC and DLCO(r=-0.46, -0.58, P<0.01), the level of serum KL-6 was positively correlated with pulmonary HRCT reticular pattern and honeycombing scores(r=0.62, 0.41, P<0.05). CONCLUSIONS: In patients with IPF, the levels of KL 6 in serum and BALF were increased and the level of KL-6 in serum was correlated with FVC, DLCO and pulmonary HRCT reticular pattern and honeycombing scores.KL-6 may be a marker for the diagnosis of IPF. PMID- 26879612 TI - [Airway metal stents removal by rigid bronchoscopy]. AB - OBJECTIVE: To explore the techniques and related complication management of airway metal stents removal with rigid bronchoscope under general anesthesia. METHODS: We reviewed 20 patients who had received rigid bronchoscopic stents removal under general anesthesia from Jan. 2008 to Jan. 2015. The clinical data were analyzed retrospectively. The indications for stents removal and potential difficulties encountered, the relationship between techniques and related complications of stents removal were discussed and analyzed, and our experiences were summarized. RESULTS: The indications for airway metal stents removal included stent migration, fracture, and granulation related in-stent restenosis. Nineteen airway metal stents were removed from 20 patients, which included 9 covered metal stents, 6 without fragmentation and 3 with fragmentation. The average duration of stenting before removal was (7.4+/-6.9)months (5 days-24 months). Of the 11 uncovered metal stents, which had stayed in the airway for (10.2+/-7.0) months (20 days-24 months), 10 were removed successfully and 1 failed. Three of them were removed intact and 7 fragmented. Complications were as follows: airway bleeding requiring management (n=11), airway collapse (n=6), re obstruction requiring temporary stent placement (n=5), postoperative tracheal intubation (n=1), mucosal tear with tracheoesophageal fistula (n=1), airway firing (n=1), airway obstruction, and death as a result of attempted stent removal (n=1). CONCLUSIONS: Airway metal stent removal is a high-risk operation. Indications for stents removal should be evaluated thoroughly and all the advantages and disadvantages should be evaluated. Once stent removal is decided, the type of the metal stent, the position of the stent implanted, the duration of stenting, and the extent of the stent embedded in granulation tissue should be carefully considered to assess the difficulty of the procedure. Dissection of the stent from the airway wall before extracting it can reduce complications such as airway bleeding, mucosal tear and airway obstruction. At the same time, a standby stent is needed to deal with possible airway collapse after stent removal. Removal of metal airway stents should only be performed by a proficient and experienced interventional pulmonology team to ensure successful operation and to improve patient safety. PMID- 26879613 TI - [The effect of renal clearance on serum trough concentration of vancomycin in elderly patients with severe pneumonia]. AB - OBJECTIVE: To investigate the effect of renal clearance on serum trough concentration of vancomycin in elderly patients with severe pneumonia. METHODS: This was a prospective non-interventional study. Forty-two elderly patients with severe pneumonia and normal level of serum creatinine were enrolled from November 2013 to October 2014. The patients included 25 males and 17 females, aged 60-83 years (median 74 years). The renal clearance was measured, and the vancomycin regimen and rate of serum trough concentration achieving guideline-recommended target of 15-20 mg/L were investigated. The factors influencing trough concentration of vancomycin were analyzed using the general linear model. RESULTS: The vancomycin regimens were 1 g/ 12 h (17 cases), 0.5 g/8 h (14 cases) and 0.5 g/12 h (11 cases), and their median and range of serum concentrations were 14.9(2.4-28.5)mg/L, 16.2(2.8-27.8)mg/L and 11.6 (5.9-19.9) mg/L, respectively. The guideline-recommended target trough concentration of 15-20 mg/L was reached in only 10 patients, while trough concentration lower than 15 mg/L was found in 22 patients and higher than 20 mg/L in 10 patients. General linear model analysis showed that creatinine clearance rate(CCR) and dose of vancomycin per kilogram of body weight per day were independent influencing factors for trough concentration (both P<0.05). There were 8 patients with CCR>=130 ml.min( 1).(1.73 m(2))(-1) (augmented renal clearance), 22 patients with 70<=CCR<130 ml.min(-1).(1.73 m(2))(-1) and 12 patients with CCR<70 ml.min(-1).(1.73 m(2))( 1,) and vancomycin trough concentration below 15 mg/L was found in 7, 11 and 4 patients, respectively. CONCLUSION: CCR was an independent influencing factor for trough concentration of vancomycin, and augmented renal clearance increased the risk of subtherapeutic trough concentration of vancomycin. PMID- 26879614 TI - [Exercise-related risk at anaerobic threshold in patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To investigate the exercise-related risk at anaerobic threshold(AT) in patients with chronic obstructive pulmonary disease(COPD). METHODS: Sixty two patients [men 56, women 6, aged (66+/-8) yr] with stable COPD in Beijing Friendship Hospital during 2013-2014, participated in this study. Incremental symptom-limited cardiopulmonary exercise test was performed on cycle ergometer. The AT was determined using the V-Slope technique and ventilatory equivalents for carbon dioxide and oxygen. Symptoms, 10-lead electrocardiogram, oxygen saturation by pulse oximetry(SpO(2)) were monitored during exercise. RESULTS: The AT, detectable in 53 patients, occurred at (68+/-10)% of peak oxygen uptake(peak VO(2)). The SpO(2) was in the safe range (94+/-2) % and the respiratory reserve was relatively high at AT (i.e. 48%). CONCLUSIONS: High-intensity exercise training can be performed in patients with moderate-to- severe COPD without resting oxygen desaturation. PMID- 26879615 TI - [Frequency and clinical relevance of rapidly growing mycobacterium isolated from respiratory samples]. AB - OBJECTIVE: To assess the frequency and clinical relevance of rapidly growing mycobacterium (RGM) isolates in a tuberculosis referral center in Beijing, China. METHODS: All isolates were identified by using targeted gene sequencing. RESULTS of species identification for 228 nontuberculous Mycobacterium (NTM) isolates from respiratory samples were analyzed, and available medical files of patients from whom NTM were isolated were reviewed retrospectively. Diagnostic criteria for RGM pulmonary disease issued by the American Thoracic Society (ATS) were used to determine clinical relevance. RESULTS: Isolates of Mycobacterium abscessus (M.abscessus) and Mycobacterium fortuitum (M.fortuitum) accounted for 28.9% (66 isolates) and 8.8% (20 isolates)of NTM isolates, respectively. Sixty-six M. abscessus isolates from 32 patients had evaluable medical files, including 28 cases diagnosed as definite M. abscessus lung disease, and 4 as probable M. abscessus lung disease. Eight M. fortuitum isolates from 8 cases had evaluable medical files, and all of them were diagnosed as unlikely lung disease. Mycobacteria Growth Indicator Tube (MGIT) was more effective to diagnose M. abscessus lung disease, as compared with Lowestein-Jensen medium (23/24 vs 18/28). CONCLUSIONS: RGM is a common NTM in our institute. M. abscessus is mostly associated with RGM lung disease, but M. fortuitum is not. PMID- 26879616 TI - [Effect of radiation dose and dose rate on pulmonary fibrosis in mice]. AB - OBJECTIVE: To study the effect of radiation dose and dose rate on radiation induced pulmonary fibrosis in mice. METHODS: Twenty-four C57BL/6 mice were randomly divided into a control group (n=6) and an irradiation group(n=18). The irradiation group was further assigned to 3 subgroups according to the whole lung radiation with 15 Gy at 400 cGy/min, 20 Gy at 400 cGy/min and 20 Gy at 100 cGy/min, while the control group received sham-irradiation. All mice were scanned with computed tomograph (CT) 20 weeks post-irradiation, and then they were sacrificed and lung tissues were collected. H&E staining, sirius red staining, lung fibrosis scored and hydroxyproline content analysis were used to assess lung fibrosis and collagen deposition. Real time PCR was used to measure the mRNA expression of type I collagen. Immunohistochemical staining was used to detect the activatin and distribution of a-SMA(+) -myofibroblasts. RESULTS: Compared to the control group, mice from irradiation groups exhibited significant pulmonary consolidation and collagen deposition.At the same dose rate, the higher irradiated dose used, the more severe pulmonary fibrosis was.On the other hand, with the same dose, the dose rate had less effect on pulmonary fibrosis. CONCLUSION: The effect of radiation dose on the degree of pulmonary fibrosis in mice is more than effect of the dose rate. PMID- 26879617 TI - [Progress of studies on clinical pharmacokinetics of inhaled antibacterials]. PMID- 26879618 TI - [Dieulafoy's disease of the bronchus]. PMID- 26879619 TI - [Research progress of venous thromboembolism in patients with acute exacerbations of COPD]. PMID- 26879620 TI - [Characteristics of neuromuscular disease related sleep disordered breathing]. PMID- 26879621 TI - [Idiopathic pulmonary fibrosis and gastro-esophageal reflux]. PMID- 26879622 TI - [Acute exacerbation of chronic obstractive pulmonary disease related to human rhinovirus]. PMID- 26879623 TI - Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval. AB - Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference. PMID- 26879625 TI - Comparing Ullmann Coupling on Noble Metal Surfaces: On-Surface Polymerization of 1,3,6,8-Tetrabromopyrene on Cu(111) and Au(111). AB - The on-surface polymerization of 1,3,6,8-tetrabromopyrene (Br4 Py) on Cu(111) and Au(111) surfaces under ultrahigh vacuum conditions was investigated by a combination of scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations. Deposition of Br4 Py on Cu(111) held at 300 K resulted in a spontaneous debromination reaction, generating the formation of a branched coordination polymer network stabilized by C-Cu-C bonds. After annealing at 473 K, the C-Cu-C bonds were converted to covalent C-C bonds, leading to the formation of a covalently linked molecular network of short oligomers. In contrast, highly ordered self-assembled two-dimensional (2D) patterns stabilized by both Br-Br halogen and Br-H hydrogen bonds were observed upon deposition of Br4 Py on Au(111) held at 300 K. Subsequent annealing of the sample at 473 K led to a dissociation of the C-Br bonds and the formation of disordered metal-coordinated molecular networks. Further annealing at 573 K resulted in the formation of covalently linked disordered networks. Importantly, we found that the chosen substrate not only plays an important role as catalyst for the Ullmann reaction, but also influences the formation of different types of intermolecular bonds and thus, determines the final polymer network morphology. DFT calculations further support our experimental findings obtained by STM and XPS and add complementary information on the reaction pathway of Br4 Py on the different substrates. PMID- 26879624 TI - Interaction between COMT Val(158)Met polymorphism and childhood adversity affects reward processing in adulthood. AB - BACKGROUND: Accumulating evidence suggests that altered dopamine transmission may increase the risk of mental disorders such as ADHD, schizophrenia or depression, possibly mediated by reward system dysfunction. This study aimed to clarify the impact of the COMT Val(158)Met polymorphism in interaction with environmental variation (G*E) on neuronal activity during reward processing. METHODS: 168 healthy young adults from a prospective study conducted over 25years participated in a monetary incentive delay task measured with simultaneous EEG-fMRI. DNA was genotyped for COMT, and childhood family adversity (CFA) up to age 11 was assessed by a standardized parent interview. RESULTS: At reward delivery, a G*E revealed that fMRI activation for win vs. no-win trials in reward-related regions increased with the level of CFA in Met homozygotes as compared to Val/Met heterozygotes and Val homozygotes, who showed no significant effect. During the anticipation of monetary vs. verbal rewards, activation decreased with the level of CFA, which was also observed for EEG, in which the CNV declined with the level of CFA. CONCLUSIONS: These results identify convergent genetic and environmental effects on reward processing in a prospective study. Moreover, G*E effects during reward delivery suggest that stress during childhood is associated with higher reward sensitivity and reduced efficiency in processing rewarding stimuli in genetically at-risk individuals. Together with previous evidence, these results begin to define a specific system mediating interacting effects of early environmental and genetic risk factors, which may be targeted by early intervention and prevention. PMID- 26879626 TI - Evaluation of oxygen saturation values in different body positions in healthy individuals. AB - AIMS AND OBJECTIVES: The research was conducted to evaluate oxygen saturation values measured in healthy individuals in different body positions. BACKGROUND: Changes in position affect ventilation-perfusion rates, oxygen transport and lung volume in normal lungs. There have been few studies and not enough information about which positioning of a healthy individual can increase oxygenation. DESIGN: A descriptive study. METHODS: A sample of 103 healthy individuals with no chronic disease, anaemia or pain was included in the research. Individuals were positioned in five different positions: sitting upright, supine position, prone position, lying on the left side and lying on the right side. Oxygen saturation and pulse rates were then measured and recorded after the individuals held each position for ten minutes. RESULTS: It was found that the average oxygen saturation value when measured while sitting in an upright position in a chair was significantly higher than that measured when the individual was lying on the right or left side of the body. Oxygen saturation values measured in the five different body positions were significantly higher in women, in individuals below the age of 35, in those with Body Mass Indexes of below 25 kg/m(2), and in nonsmokers. CONCLUSION: All of the oxygen saturation values measured in the five different body positions were in the normal range. Although oxygen saturation values were within the normal range in the five different body positions, post hoc analysis showed that the best oxygenation was in the 'sitting upright' position while the lowest oxygenation was in the supine position. RELEVANCE TO CLINICAL PRACTICE: Based on the results of this research, it can be concluded that the differences among oxygen saturation values according to the different body positions were statistically significant. PMID- 26879627 TI - "I don't know enough to feel comfortable using them:" Women's knowledge of and perceived barriers to long-acting reversible contraceptives on a college campus. AB - OBJECTIVE: To assess multiple dimensions of long-acting reversible contraception (LARC) knowledge and perceived multi-level barriers to LARC use among a sample of college women. STUDY DESIGN: We conducted an Internet-based study of 1982 female undergraduates at a large mid-western university. Our 55-item survey used a multi level framework to measure young women's understanding of, experiences with intrauterine devices (IUD) and implants and their perceived barriers to LARC at individual, health systems and community levels. The survey included a 20-item knowledge scale. We estimated and compared LARC knowledge scores and barriers using descriptive, bivariate and linear regression statistics. RESULTS: Few college women had used (5%) or heard of (22%) LARC, and most self-reported "little" or "no" knowledge of IUDs (79%) and implants (88%). Women answered 50% of LARC knowledge items correctly (mean 10.4, range 0-20), and scores differed across sociodemographic groups (p values<.04). Factors associated with scores in multivariable models included race/ethnicity, program year, sorority participation, religious affiliation and service attendance, employment status, sexual orientation and contraceptive history. Perceived barriers to IUDs included the following: not wanting a foreign object in body (44%), not knowing enough about the method (42%), preferring a "controllable" method (42%), cost (27%), and not being in a long-term relationship (23%). Implant results were similar. "Not knowing enough" was women's primary reason for IUD (18%) and implant (22%) nonuse. CONCLUSION: Lack of knowledge (both perceived and actual) was the most common barrier among many perceived individual-, systems- and community-level factors precluding these college women's LARC use. Findings can inform innovative, multi-level interventions to improve understanding, acceptability and uptake of LARC on campuses. IMPLICATIONS: Lack of knowledge of IUDs and implants served as a primary barrier to highly effective contraceptive use among these college women. Comprehensive, patient-centered and multi-level educational public health strategies are needed to promote positive campus climates around LARC and improve family planning outcomes among this substantial reproductive-aged population. PMID- 26879629 TI - Influence of calorie reduction on DNA repair capacity of human peripheral blood mononuclear cells. AB - Caloric restrictive feeding prolongs the lifespan of a variety of model organisms like rodents and invertebrates. It has been shown that caloric restriction reduces age-related as well as overall-mortality, reduces oxidative stress and influences DNA repair ability positively. There are numerous studies underlining this, but fewer studies involving humans exist. To contribute to a better understanding of the correlation of calorie reduction and DNA repair in humans, we adapted the host cell reactivation assay to an application with human peripheral blood mononuclear cells. Furthermore, we used this reliable and reproducible assay to research the influence of a special kind of calorie reduction, namely F. X. Mayr therapy, on DNA repair capacity. We found a positive effect in all persons with low pre-existing DNA repair capacity. In individuals with normal pre-existing DNA repair capacity, no effect on DNA repair capacity was detectable. Decline of DNA repair, accumulation of oxidative DNA damages, mitochondrial dysfunction, telomere shortening as well as caloric intake are widely thought to contribute to aging. With regard to that, our results can be considered as a strong indication that calorie reduction may support DNA repair processes and thus contribute to a healthier aging. PMID- 26879628 TI - The role of top-down spatial attention in contingent attentional capture. AB - It is well known that attentional capture by an irrelevant salient item is contingent on top-down feature selection, but whether attentional capture may be modulated by top-down spatial attention remains unclear. Here, we combined behavioral and ERP measurements to investigate the contribution of top-down spatial attention to attentional capture under modified spatial cueing paradigms. Each target stimulus was preceded by a peripheral circular cue array containing a spatially uninformative color singleton cue. We varied target sets but kept the cue array unchanged among different experimental conditions. When participants' task was to search for a colored letter in the target array that shared the same peripheral locations with the cue array, attentional capture by the peripheral color cue was reflected by both a behavioral spatial cueing effect and a cue elicited N2pc component. When target arrays were presented more centrally, both the behavioral and N2pc effects were attenuated but still significant. The attenuated cue-elicited N2pc was found even when participants focused their attention on the fixed central location to identify a colored letter among an RSVP letter stream. By contrast, when participants were asked to identify an outlined or larger target, neither the behavioral spatial cueing effect nor the cue-elicited N2pc was observed, regardless of whether the target and cue arrays shared same locations or not. These results add to the evidence that attentional capture by salient stimuli is contingent upon feature-based task sets, and further indicate that top-down spatial attention is important but may not be necessary for contingent attentional capture. PMID- 26879630 TI - Mediterranean nutraceutical foods: Strategy to improve vascular ageing. AB - Ageing is characterized by a decline in all systemic functions. A greater susceptibility to apoptosis and senescence may contribute to proliferative and functional impairment of endothelial progenitor cells. They play an important role in neo-angiogenesis and endothelial repair. Vascular ageing is associated with changes in the structure and functions of vessels' wall. There are many possible causes of this damage. For sure, inflammation and oxidative stress play a fundamental role in the pathogenesis of endothelial dysfunction, commonly attributed to a reduced availability of nitric oxide. Inflammageing, the chronic low-grade inflammation that characterizes elderly people, aggravates vascular pathology and provokes atherosclerosis, the major cardiovascular disease. Nutraceutical and molecular biology represent new insights in this field. In fact, the first could represent a possible treatment in the prevention or delay of vascular ageing; the second could offer new possible targets for potential therapeutic interventions. In this review, we pay attention on the causes of vascular ageing and on the effects of nutraceuticals on it. PMID- 26879631 TI - Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection. AB - BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. METHODS: TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. RESULTS: Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV alpha1alpha1alpha2 heterotrimers. The mutation was predicted to be damaging. CONCLUSION: We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors. PMID- 26879632 TI - Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior. AB - Associative learning is thought to require coordinated activities among distributed brain regions. For example, to direct behavior appropriately, the medial prefrontal cortex (mPFC) must encode and maintain sensory information and then interact with the cerebellum during trace eyeblink conditioning (TEBC), a commonly-used associative learning model. However, the mechanisms by which these two distant areas interact remain elusive. By simultaneously recording local field potential (LFP) signals from the mPFC and the cerebellum in guinea pigs undergoing TEBC, we found that theta-frequency (5.0-12.0 Hz) oscillations in the mPFC and the cerebellum became strongly synchronized following presentation of auditory conditioned stimulus. Intriguingly, the conditioned eyeblink response (CR) with adaptive timing occurred preferentially in the trials where mPFC cerebellum theta coherence was stronger. Moreover, both the mPFC-cerebellum theta coherence and the adaptive CR performance were impaired after the disruption of endogenous orexins in the cerebellum. Finally, association of the mPFC cerebellum theta coherence with adaptive CR performance was time-limited occurring in the early stage of associative learning. These findings suggest that the mPFC and the cerebellum may act together to contribute to the adaptive performance of associative learning behavior by means of theta synchronization. PMID- 26879633 TI - Can a Home-based Cardiac Physical Activity Program Improve the Physical Function Quality of Life in Children with Fontan Circulation? AB - OBJECTIVE: Patients after Fontan operation for complex congenital heart disease (CHD) have decreased exercise capacity and report reduced health-related quality of life (HRQOL). Studies suggest hospital-based cardiac physical activity programs can improve HRQOL and exercise capacity in patients with CHD; however, these programs have variable adherence rates. The impact of a home-based cardiac physical activity program in Fontan survivors is unclear. This pilot study evaluated the safety, feasibility, and benefits of an innovative home-based physical activity program on HRQOL in Fontan patients. METHODS: A total of 14 children, 8-12 years, with Fontan circulation enrolled in a 12-week moderate/high intensity home-based cardiac physical activity program, which included a home exercise routine and 3 formalized in-person exercise sessions at 0, 6, and 12 weeks. Subjects and parents completed validated questionnaires to assess HRQOL. The Shuttle Test Run was used to measure exercise capacity. A Fitbit Flex Activity Monitor was used to assess adherence to the home activity program. RESULTS: Of the 14 patients, 57% were male and 36% had a dominant left ventricle. Overall, 93% completed the program. There were no adverse events. Parents reported significant improvement in their child's overall HRQOL (P < .01), physical function (P < .01), school function (P = .01), and psychosocial function (P < .01). Patients reported no improvement in HRQOL. Exercise capacity, measured by total shuttles and exercise time in the Shuttle Test Run and calculated VO2 max, improved progressively from baseline to the 6 and 12 week follow up sessions. Monthly Fitbit data suggested adherence to the program. CONCLUSION: This 12-week home-based cardiac physical activity program is safe and feasible in preteen Fontan patients. Parent proxy-reported HRQOL and objective measures of exercise capacity significantly improved. A 6-month follow up session is scheduled to assess sustainability. A larger study is needed to determine the applicability and reproducibility of these findings in other age groups and forms of complex CHD. PMID- 26879634 TI - Effects of bariatric surgery on male lower urinary tract symptoms and sexual function. AB - AIM: To investigate the effect of bariatric surgery on male lower urinary tract symptoms (LUTS) and sexual function. METHODS: Fifty-five consecutive obese men who underwent a laparoscopic sleeve gastrectomy were prospectively enrolled. Two validated questionnaires, the International Prostate Symptoms Score (IPSS) and the International Index of Erectile Function (IIEF) were used to assess LUTS and sexual function, before and 3 months after surgery. Fifty-three men (mean age 39 +/- 12.5 years) completed all pre and postoperative questionnaires. Mean body mass index (BMI) before and 3 months after surgery was 42.8 +/- 5.3 and 31.3 +/- 5.4 kg/m2 ; respectively. RESULTS: Preoperatively, 41 (77%) men (mean age 40 +/- 12.9, mean BMI 42.2 +/- 5 kg/m2 ) had some degree of LUTS and 39 (74%) men (mean age 40.7 +/- 12.4, mean BMI 42.8 +/- 5.6 kg/m2 ) were sexually active. Postoperatively, the total IPSS score decreased significantly (5.5 +/- 4.4 vs. 2.7 +/- 2.6; P < 0.001), however this change was due to improvement in storage phase LUTS, measured by questions 2, 4, and 7 of the IPSS questionnaire. No statistically significant changes of voiding phase LUTS, measured by questions 1, 3, 5, 6 of the IPSS, were observed. Of the various aspects of sexual dysfunction, only erectile function, measured by questions 1-5 and 15 of the IIEF questionnaire was significantly improved (22.7 +/- 7.2 vs. 26.1 +/- 6.5, P = 0.02). Postoperative overall intercourse satisfaction (9.5 +/- 4.2 vs. 11.5 +/- 3, P = 0.01) and overall satisfaction (7.9 +/- 2.5 vs. 8.9 +/- 1.3, P = 0.02) were significantly improved as well. CONCLUSION: Male storage phase LUTS and erectile function were significantly and rapidly improved following bariatric surgery. Larger and long-term studies are required to investigate these apparently beneficial effects. Neurourol. Urodynam. 36:636-639, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26879635 TI - Imaging synucleinopathies. AB - In this review the structural and functional imaging changes associated with the synucleinopathies PD, MSA, and dementias associated with Lewy bodies are reviewed. The role of imaging for supporting differential diagnosis, detecting subclinical disease, and following disease progression is discussed and its potential use for monitoring disease progression is debated. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26879636 TI - Prevalence and correlates of proteinuria in Kampala, Uganda: a cross-sectional pilot study. AB - BACKGROUND: Despite the increasing prevalence of chronic kidney disease (CKD) in sub-Saharan Africa, few community-based screenings have been conducted in Uganda. Opportunities to improve the management of CKD in sub-Saharan Africa are limited by low awareness, inadequate access, poor recognition, and delayed presentation for clinical care. Therefore, the Uganda Kidney Foundation engaged key stakeholders in performing a screening event on World Kidney Day. METHODS: We conducted a cross-sectional pilot study in March 2013 from a convenience sample of adult, urban residents in Kampala, Uganda. We advertised the event using radio and television announcements, newspapers, billboards, and notice boards at public places, such as places of worship. Subsequently, we screened for proteinuria, hypertension, fasting glucose impairment, and obesity in a central and easily accessible location. RESULTS: We enrolled 141 adults most of whom were female (57 %), young (64 %; 18-39 years), and had a professional occupation (52 %). The prevalence of proteinuria (13 %; 95 % confidence interval [CI] 7-19 %), hypertension (38 %; 95 % CI 31-47 %), and impaired fasting glucose (13 %; 95 % CI 9-20 %) were high in this study population. Proteinuria was most prevalent among young (18-39 years) adults (n = 14; 16 %) and among those who reported a history of alcohol intake (n = 10; 32 %). CONCLUSIONS: The prevalence of proteinuria was high among a convenience sample of urban residents in a sub-Saharan African setting. These results represent an important effort by the Ugandan Kidney Foundation to increase awareness and recognition of CKD, and they will help formulate additional epidemiological studies on NCDs in Uganda which are urgently needed and now feasible. PMID- 26879637 TI - High-Contrast Gratings based Spoof Surface Plasmons. AB - In this work, we explore the existence of spoof surface plasmons (SSPs) supported by deep-subwavelength high-contrast gratings (HCGs) on a perfect electric conductor plane. The dispersion relation of the HCGs-based SSPs is derived analyt ically by combining multimode network theory with rigorous mode matching method, which has nearly the same form with and can be degenerated into that of the SSPs arising from deep-subwavelength metallic gratings (MGs). Numerical simula- tions validate the analytical dispersion relation and an effective medium approximation is also presented to obtain the same analytical dispersion formula. This work sets up a unified theoretical framework for SSPs and opens up new vistas in surface plasmon optics. PMID- 26879638 TI - Positive deviance as a novel tool in malaria control and elimination: methodology, qualitative assessment and future potential. AB - BACKGROUND: Positive deviance (PD) is an asset-based, community-driven approach to behaviour change that has successfully been applied to address many health and social problems. It is yet to have been assessed for malaria control but may represent a promising tool for malaria elimination given its suitability in targeting small and remote population groups, apparent sustainability and ability to instil a high amount of community mobilisation. Here, the PD methodology as applied to malaria is explained, with focus upon and qualitative assessment of a proof of concept study in Cambodia. METHODS: Three villages in Battambang, northwestern Cambodia were selected for the intervention, with an estimated population of 5036 including both residents and migrant workers. In August 2010, field teams conducted a 1 week PD process to sensitise and mobilise the community, establish normative behaviours in relation to malaria control and prevention, identify positive deviant behaviours from within the community, and identify PD volunteers. Until March 2011, PD volunteers were supported by field teams via monthly meetings to conduct activities in their respective communities to increase practice of PD behaviours. In February 2012, 1 year following the end of external support, evaluative interviews were conducted with community members to qualitatively assess community acceptance and interpretation of the PD intervention, perceived behaviour changes, and perceived positive outcomes. RESULTS: Qualitative data from focus group discussions and in-depth interviews showed that the PD approach was well-accepted into the communities and created a strong sense of community empowerment. Positive behaviour change was linked to the PD intervention, including greater usage of nets by forest goers, and use of public health facilities for malaria diagnosis and treatment. One year following the end of external assistance, PD volunteers were still conducting activities in their respective communities. CONCLUSIONS: PD offers a promising tool in malaria control and elimination settings. Work is ongoing to quantitatively measure impact of PD on behaviours and malaria transmission and once gathered, national malaria control programmes should be encouraged to look at including PD as part of their national strategies. Feasibility of scale-up, cost-effectiveness, and applicability to other settings and diseases is also currently being explored. PMID- 26879640 TI - Integrating geological archives and climate models for the mid-Pliocene warm period. AB - The mid-Pliocene Warm Period (mPWP) offers an opportunity to understand a warmer than-present world and assess the predictive ability of numerical climate models. Environmental reconstruction and climate modelling are crucial for understanding the mPWP, and the synergy of these two, often disparate, fields has proven essential in confirming features of the past and in turn building confidence in projections of the future. The continual development of methodologies to better facilitate environmental synthesis and data/model comparison is essential, with recent work demonstrating that time-specific (time-slice) syntheses represent the next logical step in exploring climate change during the mPWP and realizing its potential as a test bed for understanding future climate change. PMID- 26879639 TI - RAB18, a protein associated with Warburg Micro syndrome, controls neuronal migration in the developing cerebral cortex. AB - BACKGROUND: Loss of function mutations in RAB18, has been identified in patients with the human neurological and developmental disorder Warburg Micro syndrome. However, the function of RAB18 in brain remains unknown. RESULTS: In this study, we report that RAB18 is a critical regulator of neuronal migration and morphogenesis. Using in utero electroporation suppression of RAB18 in the mouse brain impairs radial migration. Overexpression of dominant negative RAB18 or disruption of RAB3GAP (RAB18GEF) also results in delayed neuronal migration in the developing mouse cortex and inhibition of neurite growth in vitro. Moreover, loss of RAB18 induces an acceleration of N-cadherin degradation by lysosomal pathway resulting in the decrease of surface level of N-cadherin on neurons. CONCLUSIONS: RAB18 regulates neuronal migration and morphogenesis during development. Our findings highlight the critical role of RAB3GAP-RAB18 pathway in the developing cerebral cortex and might explain some of clinical features observed in patients with Warburg Micro syndrome. PMID- 26879641 TI - The reactivation of tabun-inhibited mutant AChE with Ortho-7: steered molecular dynamics and quantum chemical studies. AB - A highly toxic nerve agent, tabun, can inhibit acetylcholinesterase (AChE) at cholinergic sites, which leads to serious cardiovascular complications, respiratory compromise and death. We have examined the structural features of the tabun-conjugated AChE complex with an oxime reactivator, Ortho-7, to provide a strategy for designing new and efficient reactivators. Mutation of mAChE within the choline binding site by Y337A and F338A and its interaction with Ortho-7 has been investigated using steered molecular dynamics (SMD) and quantum chemical methods. The overall study shows that after mutagenesis (Y337A), the reactivator can approach more freely towards the phosphorylated active site of serine without any significant steric hindrance in the presence of tabun compared to the wild type and double mutant. Furthermore, the poor binding of Ortho-7 with the peripheral residues of mAChE in the case of the single mutant compared to that of the wild-type and double mutant (Y337A/F338A) can contribute to better efficacy in the former case. Ortho-7 has formed a greater number of hydrogen bonds with the active site surrounding residues His447 and Phe295 in the case of the single mutant (Y337A), and that stabilizes the drug molecule for an effective reactivation process. The DFT M05-2X/6-31+G(d) level of theory shows that the binding energy of Ortho-7 with the single mutant (Y337A) is energetically more preferred (-19.8 kcal mol(-1)) than the wild-type (-8.1 kcal mol(-1)) and double mutant (Y337A/F338A) (-16.0 kcal mol(-1)). The study reveals that both the orientation of the oxime reactivator for nucleophilic attack and the stabilization of the reactivator at the active site would be crucial for the design of an efficient reactivator. PMID- 26879642 TI - A facile and efficient method of enzyme immobilization on silica particles via Michael acceptor film coatings: immobilized catalase in a plug flow reactor. AB - A novel method was developed for facile immobilization of enzymes on silica surfaces. Herein, we describe a single-step strategy for generating of reactive double bonds capable of Michael addition on the surfaces of silica particles. This method was based on reactive thin film generation on the surfaces by heating of impregnated self-curable polymer, alpha-morpholine substituted poly(vinyl methyl ketone) p(VMK). The generated double bonds were demonstrated to be an efficient way for rapid incorporation of enzymes via Michael addition. Catalase was used as model enzyme in order to test the effect of immobilization methodology by the reactive film surface through Michael addition reaction. Finally, a plug flow type immobilized enzyme reactor was employed to estimate decomposition rate of hydrogen peroxide. The highly stable enzyme reactor could operate continuously for 120 h at 30 degrees C with only a loss of about 36 % of its initial activity. PMID- 26879644 TI - Monitoring of an antigen manufacturing process. AB - Fluorescence spectroscopy in combination with multivariate statistical methods was employed as a tool for monitoring the manufacturing process of pertactin (PRN), one of the virulence factors of Bordetella pertussis utilized in whopping cough vaccines. Fluorophores such as amino acids and co-enzymes were detected throughout the process. The fluorescence data collected at different stages of the fermentation and purification process were treated employing principal component analysis (PCA). Through PCA, it was feasible to identify sources of variability in PRN production. Then, partial least square (PLS) was employed to correlate the fluorescence spectra obtained from pure PRN samples and the final protein content measured by a Kjeldahl test from these samples. In view that a statistically significant correlation was found between fluorescence and PRN levels, this approach could be further used as a method to predict the final protein content. PMID- 26879643 TI - Hybrid modeling as a QbD/PAT tool in process development: an industrial E. coli case study. AB - Process understanding is emphasized in the process analytical technology initiative and the quality by design paradigm to be essential for manufacturing of biopharmaceutical products with consistent high quality. A typical approach to developing a process understanding is applying a combination of design of experiments with statistical data analysis. Hybrid semi-parametric modeling is investigated as an alternative method to pure statistical data analysis. The hybrid model framework provides flexibility to select model complexity based on available data and knowledge. Here, a parametric dynamic bioreactor model is integrated with a nonparametric artificial neural network that describes biomass and product formation rates as function of varied fed-batch fermentation conditions for high cell density heterologous protein production with E. coli. Our model can accurately describe biomass growth and product formation across variations in induction temperature, pH and feed rates. The model indicates that while product expression rate is a function of early induction phase conditions, it is negatively impacted as productivity increases. This could correspond with physiological changes due to cytoplasmic product accumulation. Due to the dynamic nature of the model, rational process timing decisions can be made and the impact of temporal variations in process parameters on product formation and process performance can be assessed, which is central for process understanding. PMID- 26879645 TI - Fluorinated graphenes as advanced biosensors - effect of fluorine coverage on electron transfer properties and adsorption of biomolecules. AB - Graphene derivatives are promising materials for the electrochemical sensing of diverse biomolecules and development of new biosensors owing to their improved electron transfer kinetics compared to pristine graphene. Here, we report complex electrochemical behavior and electrocatalytic performance of variously fluorinated graphene derivatives prepared by reaction of graphene with a nitrogen fluorine mixture at 2 bars pressure. The fluorine content was simply controlled by varying the reaction time and temperature. The studies revealed that electron transfer kinetics and electrocatalytic activity of CFx strongly depend on the degree of fluorination. The versatility of fluorinated graphene as a biosensor platform was demonstrated by cyclic voltammetry for different biomolecules essential in physiological processes, i.e. NADH, ascorbic acid and dopamine. Importantly, the highest electrochemical performance, even higher than pristine graphene, was obtained for fluorinated graphene with the lowest fluorine content (CF0.084) due to its high conductivity and enhanced adsorption properties combining pi-pi stacking interaction with graphene regions with hydrogen-bonding interaction with fluorine atoms. PMID- 26879646 TI - Characterization of rhamnolipids by liquid chromatography/mass spectrometry after solid-phase extraction. AB - Rhamnolipids are surface-active agents with a broad application potential that are produced in complex mixtures by bacteria of the genus Pseudomonas. Analysis from fermentation broth is often characterized by laborious sample preparation and requires hyphenated analytical techniques like liquid chromatography coupled to mass spectrometry (LC-MS) to obtain detailed information about sample composition. In this study, an analytical procedure based on chromatographic method development and characterization of rhamnolipid sample material by LC-MS as well as a comparison of two sample preparation methods, i.e., liquid-liquid extraction and solid-phase extraction, is presented. Efficient separation was achieved under reversed-phase conditions using a mixed propylphenyl and octadecylsilyl-modified silica gel stationary phase. LC-MS/MS analysis of a supernatant from Pseudomonas putida strain KT2440 pVLT33_rhlABC grown on glucose as sole carbon source and purified by solid-phase extraction revealed a total of 20 congeners of di-rhamnolipids, mono-rhamnolipids, and their biosynthetic precursors 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs) with different carbon chain lengths from C8 to C14, including three rhamnolipids with uncommon C9 and C11 fatty acid residues. LC-MS and the orcinol assay were used to evaluate the developed solid-phase extraction method in comparison with the established liquid liquid extraction. Solid-phase extraction exhibited higher yields and reproducibility as well as lower experimental effort. PMID- 26879647 TI - Quantification of a peptide standard using the intrinsic fluorescence of tyrosine. AB - Absolute quantification of peptides is typically achieved using amino acid analysis, elemental analysis or derivatisation chemistry. Impurities, if present, may be accounted for using analytical high-performance liquid chromatography (HPLC) with detection of the peptide bond ultraviolet (UV) absorbance. To do this, peak areas from a UV chromatogram are used to estimate percentage purity on a mass basis, and this purity value is used as a correction. However, because the approach assumes that UV absorbance is uniformly proportional to mass, the result may be only semi-quantitative. Here, an alternative approach involving HPLC with detection of intrinsic tyrosine fluorescence is described. The fluorescence properties of a 21-residue synthetic peptide corresponding to an S carbamidomethylated tryptic fragment of human serum albumin were characterised, and a method involving quantification relative to a non-peptidic calibrant, N acetyl-L-tyrosine ethyl ester, was established. The method was used to quantify the thiol form of the peptide, and the results were compared with a parallel analysis involving derivatisation of the same material with Ellman's reagent. When differences in fluorescence response (analyte versus calibrant) were accounted for, the measurements obtained via the two methods were in good agreement. Contributions from peptidic impurities were also considered, and their influence on the validity of the conclusions was evaluated. Despite some ambiguities introduced by the impurities, and the identification of some other potential sources of error, the results demonstrate that use of Tyr fluorescence is a promising solution to the challenging problem of absolute peptide quantification. PMID- 26879648 TI - Label-free and sensitive aptasensor based on dendritic gold nanostructures on functionalized SBA-15 for determination of chloramphenicol. AB - A highly sensitive and low-cost electrochemical aptasensor was developed for the determination of chloramphenicol (CAP). The system was based on a CAP-binding aptamer, a molecular recognition element, and 1,4-diazabicyclo[2.2.2]octane (DABCO)-supported mesoporous silica SBA-15 on the surface of a screen-printed graphite electrode for formation of dendritic gold nanostructures and improving the performance and conductivity of the biosensor. Hemin has been applied as an electrochemical indicator which interacted with the guanine bases of the aptamer. In the absence of CAP, hemin binds to the aptamer and produces a weak differential pulse voltammetric (DPV) signal. The presence of CAP led to stabilization of the folded aptamer, which generated an amplified DPV signal. The peak current of hemin increased linearly with the concentration of CAP. Under optimal conditions, two linear ranges were obtained from 0.03 to 0.15 MUM and 0.15 to 7.0 MUM, respectively, and the detection limit was 4.0 nM. The prepared biosensor has good selectivity against other non-target drugs. Thus, the sensor could provide a promising platform for the fabrication of aptasensors. The feasibility of using this aptasensor was demonstrated by determination of CAP in a human blood serum sample. PMID- 26879649 TI - Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS. AB - The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIATM D.A.R.T.'S(r) (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19 37%), lower limit of detection (<50 pg/mL), imprecision (<20%), and ion suppression/enhancement effects. The analytes' stability and metabolism were elucidated using in vitro and in vivo approaches. EDTA blood samples were collected from rats 2, 4, and 8 h after intravenous administration of GHRH (one compound per test animal). All intact substances were detected for at least 4 h but no anticipated metabolite was confirmed in laboratory rodents' samples; conversely, a Geref metabolite (GHRH3-29) was found in a human plasma sample collected after subcutaneous injection of the drug to a healthy male volunteer. The obtained results demonstrate that GHRHs are successfully detected in plasma using an immunoaffinity-mass spectrometry-based method, which can be applied to sports drug testing samples. Further studies are however required and warranted to account for potential species-related differences in metabolism and elimination of the target analytes. PMID- 26879650 TI - Mid-infrared spectroscopy for protein analysis: potential and challenges. AB - Mid-infrared (MIR) spectroscopy investigates the interaction of MIR photons with both organic and inorganic molecules via the excitation of vibrational and rotational modes, providing inherent molecular selectivity. In general, infrared (IR) spectroscopy is particularly sensitive to protein structure and structural changes via vibrational resonances originating from the polypeptide backbone or side chains; hence information on the secondary structure of proteins can be obtained in a label-free fashion. In this review, the challenges for IR spectroscopy for protein analysis are discussed as are the potential and limitations of different IR spectroscopic techniques enabling protein analysis. In particular, the amide I spectral range has been widely used to study protein secondary structure, conformational changes, protein aggregation, protein adsorption, and the formation of amyloid fibrils. In addition to representative examples of the potential of IR spectroscopy in various fields related to protein analysis, the potential of protein analysis taking advantage of miniaturized MIR systems, including waveguide-enhanced MIR sensors, is detailed. PMID- 26879651 TI - Identification of adverse events that have a negative impact on quality of life in a clinical trial comparing docetaxel versus S-1 with cisplatin in lung cancer. AB - PURPOSE: In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL. METHODS: QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05). RESULTS: As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm. CONCLUSION: An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy. PMID- 26879652 TI - Tumor angiogenesis--characteristics of tumor endothelial cells. AB - Tumor blood vessels provide nutrition and oxygen to the tumor, resulting in tumor progression. They also act as gatekeepers, inducing tumor metastasis. Thus, targeting tumor blood vessels is an important strategy in cancer therapy. Tumor endothelial cells (TECs), which line the inner layer of blood vessels of the tumor stromal tissue, are the main targets of anti-angiogenic therapy. Because new tumor blood vessels generally sprout from pre-existing vasculature, they have been considered to be the same as normal blood vessels. However, tumor blood vessels demonstrate a markedly abnormal phenotype that includes several important morphological changes. The degree of angiogenesis is determined by the balance between the angiogenic stimulators and inhibitors released by the tumor and host cells. Recent studies have revealed that TECs also exhibit altered characteristics which depend on the tumor microenvironment. Here, we review recent studies on TEC abnormalities and heterogeneity with respect to tumor progression and consider their therapeutic implications. PMID- 26879653 TI - HIV Self-Testing: a Review of Current Implementation and Fidelity. AB - Oral HIV self-testing is an innovative and potentially high-impact means to increase HIV-case identification globally. As a screening test, oral HIV self testing offers the potential for increased adoption through greater convenience and privacy, and the potential to increase the proportion of the population who test regularly. Research on how best to translate the innovation of oral self testing to high-risk populations is underway. Currently only one oral HIV self test kit is FDA-approved (OraQuick In-Home HIV Test) and available for retail sale. In the present report we review recent studies on the dissemination, adoption, and implementation of oral HIV testing. Prior work has focused primarily on adoption, but recent studies have begun to identify methods for improving dissemination and problems associated with self-implementation. At present a major barrier to wider adoption is the relatively high retail cost of the oral HIV test kit. Significant but minor barriers are represented by overly complex instructional materials for some population segments, and dissemination programs of unknown efficacy. Theoretical and practical suggestions for conducting research on dissemination, adoption, and implementation of oral HIV testing are discussed. PMID- 26879655 TI - The child and adolescent with HIV in resource poor countries. AB - Although sub-Saharan Africa caries the burden of paediatric and adult HIV/AIDS infections, the epidemic is spreading most rapidly in the Middle East and North Africa Region where between 2005 and 2013, AIDS-related deaths increased by 66% in comparison with a worldwide fall of 35%. For the first time, in 2011, more than half of people in need of antiretroviral drugs were receiving them, with coverage reaching 54%; yet only 28% of children have access to HIV treatment. This review sought to provide an update of paediatric and adolescent oral HIV/AIDS issues in resource poor countries. OBJECTIVES: To review the literature on paediatric & adolescent HIV with a focus on oral lesions as predictors of HIV infection; as markers of the efficacy of HAART and quality of life; caries risk; management of oral lesions; and epidemiological tests for clinical significance of oral lesions. METHODS: A search strategy was developed for PubMed to identify papers on paediatric oral HIV. Publications in English were selected on the basis that their titles and abstracts were relevant to the review objectives. The reference lists of included papers were screened for additional articles. The time-search for publications was limited from 2009 to 15 October 2014. RESULTS: Papers on the prevalence of oral lesions lacked standardization in diagnostic criteria and the introduction of HAART had significantly reduced prevalence; oral lesions remain useful predictors for HIV infection and as markers for the efficacy of HAART. Evidence suggest that caries risk is increased with HIV infection; management of oral lesions is inconsistent with available resources and surprisingly little recent information has been published in the past 5 years. Revised case definitions are proposed for large-scale epidemiologic studies with the development of an oral lesion index showing promise. Oral health quality of life indicators for children and adolescents are becoming important as more of these indicators are being developed and their negative oral impacts in individuals with oral lesions are now well established. CONCLUSIONS: Paediatric and adolescent oral HIV research needs to be prioritized as current studies are few and are characterized by poor quality study designs, small study samples and a lack of multicentre collaborations. There is a lack of high quality evidence for a number of interventions available for management of oral lesions. PMID- 26879656 TI - Rectal arterio-venous malformation (AVM) with bleeding of an internal hemorrhoid. AB - A 38-year-old male with no past history of illnesses visited the out-patient clinic of Nerima Hikarigaoka Hospital complaining of dizziness and persistent anal bleeding. There was a significant anemia on a blood test and colonoscopy showed a thrombus in a markedly swollen internal hemorrhoid. Contrast-enhanced computed tomography (CT) showed a poorly demarcated area with early face enhancement on the right side of the rectum and anal canal. Based on these findings, an arterio-venous malformation (AVM) of the rectum was suspected. Abdominal angiography showed abnormal vessels receiving a blood supply from the bilateral superior rectal arteries. We suspected that the AVM in the rectum was the cause of the hemorrhage from the internal hemorrhoid, and therefore performed embolization of the AVM. Thereafter, the hemorrhage from the internal hemorrhoid stopped completely and the anemia improved to the normal level, without the need for treatment for the internal hemorrhoid. Colonoscopy performed 6 months after embolization showed shrinkage of the internal hemorrhoid. To the best of our knowledge, there are no reports stating a relationship between rectal AVM and internal hemorrhoids. However, we consider that contrast-enhanced CT can be used to detect vessel abnormalities related to severe bleeding of the internal hermorrhoids in patients with internal hemorrhoids and severe anemia. PMID- 26879657 TI - Commentaries on Viewpoint: A role for the prefrontal cortex in exercise tolerance and termination. PMID- 26879654 TI - Friend or Foe: Innate Sensing of HIV in the Female Reproductive Tract. AB - The female reproductive tract (FRT) is a major site for human immunodeficiency virus (HIV) infection. There currently exists a poor understanding of how the innate immune system is activated upon HIV transmission and how this activation may affect systemic spread of HIV from the FRT. However, multiple mechanisms for how HIV is sensed have been deciphered using model systems with cell lines and peripheral blood-derived cells. The aim of this review is to summarize recent progress in the field of HIV innate immune sensing and place this in the context of the FRT. Because HIV is somewhat unique as an STD that thrives under inflammatory conditions, the response of cells upon sensing HIV gene products can either promote or limit HIV infection depending on the context. Future studies should include investigations into how FRT-derived primary cells sense and respond to HIV to confirm conclusions drawn from non-mucosal cells. Understanding how cells of the FRT participate in and effect innate immune sensing of HIV will provide a clearer picture of what parameters during the early stages of HIV exposure determine transmission success. Such knowledge could pave the way for novel approaches for preventing HIV acquisition in women. PMID- 26879658 TI - Last Word on Viewpoint: A role for the prefrontal cortex in exercise tolerance and termination. PMID- 26879659 TI - Commentaries on Viewpoint: A call for research to assess and promote functional resilience in astronaut crews. PMID- 26879660 TI - Last Word on Viewpoint: A call for research to assess and promote functional resilience in astronaut crews. PMID- 26879661 TI - No functional reserve at exhaustion in endurance-trained men? PMID- 26879663 TI - Patient and Clinician Assessments of Symptomatology Changes on Older Adults Following a Psycho-educational Program for Depression and Anxiety. AB - Important attention has been given to the assessment of patients' perspectives on treatment, especially as outcomes have been typically evaluated by clinicians. This study examined the association between patient and clinician ratings on perceived improvement and symptomatology changes for an older adult population participating in an ongoing psycho-educational program. Pre-post measures including depression (GDS), anxiety (BAI) and general well-being (GWBS) were collected in a sample of 34 older adults (age = 71.32 +/- 6.46 years). Post testing data included perceived improvement rated by patients, and clinician assessment of depressive symptoms (CS-GDS). Results indicate significant correlations between pre-post changes of the GDS and patients' PIQ (r = -0.37, n = 31, p < 0.05), but not on symptomatic changes of the BAI (r = 0.012, n = 32, p > 0.05) or the GWBS (r = 0.12, n = 31, p > 0.05). Relationships between patients' PIQ and post-ratings on GDS (r = -0.74, n = 33, p < 0.05) and CS-GDS (r = -0.48, n = 32, p < 0.05) are also significant. Results imply that pre-post improvement in depressive symptoms is associated with a patient's perceived improvement and that clinician and patient ratings on depression symptoms post-treatment were both inversely correlated to patients' perceived improvement. Findings suggest that the PIQ is a good indicator to assess symptomatic change by patients and clinicians although they are possibly placing attention on different aspects of treatment outcome, as indicated by differences on sub-scales of the PIQ. Clinicians possibly place a strong focus on assessments of depression symptomatology. Future studies may integrate simultaneous assessments of instruments exploring aspects other than depression, especially those examining representations of illness in older adults. PMID- 26879664 TI - Erratum to: Recombinant viral protein VP1 suppresses HER-2 expression and migration/metastasis of breast cancer. PMID- 26879662 TI - Impact of the beta-1 adrenergic receptor polymorphism on tolerability and efficacy of bisoprolol therapy in Korean heart failure patients: association between beta adrenergic receptor polymorphism and bisoprolol therapy in heart failure (ABBA) study. AB - BACKGROUND/AIMS: We evaluated the association between coding region variants of adrenergic receptor genes and therapeutic effect in patients with congestive heart failure (CHF). METHODS: One hundred patients with stable CHF (left ventricular ejection fraction [LVEF] < 45%) were enrolled. Enrolled patients started 1.25 mg bisoprolol treatment once daily, then up-titrated to the maximally tolerable dose, at which they were treated for 1 year. RESULTS: Genotypic analysis was carried out, but the results were blinded to the investigators throughout the study period. At position 389 of the beta-1 adrenergic receptor gene (ADRB1), the observed minor Gly allele frequency (Gly389Arg + Gly389Gly) was 0.21, and no deviation from Hardy-Weinberg equilibrium was observed in the genotypic distribution of Arg389Gly (p = 0.75). Heart rate was reduced from 80.8 +/- 14.3 to 70.0 +/- 15.0 beats per minute (p < 0.0001). There was no significant difference in final heart rate across genotypes. However, the Arg389Arg genotype group required significantly more bisoprolol compared to the Gly389X (Gly389Arg + Gly389Gly) group (5.26 +/- 2.62 mg vs. 3.96 +/- 2.05 mg, p = 0.022). There were no significant differences in LVEF changes or remodeling between two groups. Also, changes in exercise capacity and brain natriuretic peptide level were not significant. However, interestingly, there was a two-fold higher rate of readmission (21.2% vs. 10.0%, p = 0.162) and one CHF-related death in the Arg389Arg group. CONCLUSIONS: The ADRB1 Gly389X genotype showed greater response to bisoprolol than the Arg389Arg genotype, suggesting the potential of individually tailoring beta-blocker therapy according to genotype. PMID- 26879665 TI - Sequential learning of relative size by the Neotropical ant Gigantiops destructor. AB - The question of whether insects can perform concept learning or can use the geometry of space as in mammals has been recently addressed in Hymenoptera in an extensive way. We investigate here the ability of the tropical ant Gigantiops destructor to perform sequential learning and to use size relationships during navigation. Ants were trained to solve a dichotomic six-stage linear maze relying on the apparent width of two vertical landmarks. Each individual ant first learnt to associate a given landmark width to the motor decision of turning right or left to avoid dead-ends independently of a motor routine. When confronted for the first time with a new intermediate-sized pattern, for which no supposed snapshot could have been stored, ants made directional choices indicating that bar width judgments were not absolute but rather relative to the familiar visual patterns seen in the previous chambers. This result demonstrates that ants can generalize relationship rules by interpolating the relative width of a novel stimulus according to visual information kept in spatial working memory. In conclusion, ants can perform conditional discriminations reliably not only when stimuli are simultaneous but also when they are sequential. PMID- 26879666 TI - El grillo e buon cantore: for Franz Huber on the occasion of his 90th birthday. PMID- 26879667 TI - NETIMIS: Dynamic Simulation of Health Economics Outcomes Using Big Data. AB - Many healthcare organizations are now making good use of electronic health record (EHR) systems to record clinical information about their patients and the details of their healthcare. Electronic data in EHRs is generated by people engaged in complex processes within complex environments, and their human input, albeit shaped by computer systems, is compromised by many human factors. These data are potentially valuable to health economists and outcomes researchers but are sufficiently large and complex enough to be considered part of the new frontier of 'big data'. This paper describes emerging methods that draw together data mining, process modelling, activity-based costing and dynamic simulation models. Our research infrastructure includes safe links to Leeds hospital's EHRs with 3 million secondary and tertiary care patients. We created a multidisciplinary team of health economists, clinical specialists, and data and computer scientists, and developed a dynamic simulation tool called NETIMIS (Network Tools for Intervention Modelling with Intelligent Simulation; http://www.netimis.com ) suitable for visualization of both human-designed and data-mined processes which can then be used for 'what-if' analysis by stakeholders interested in costing, designing and evaluating healthcare interventions. We present two examples of model development to illustrate how dynamic simulation can be informed by big data from an EHR. We found the tool provided a focal point for multidisciplinary team work to help them iteratively and collaboratively 'deep dive' into big data. PMID- 26879668 TI - Nasal basal cell carcinomas. Can we reduce surgical margins to 3mm with complete excision? AB - BACKGROUND: The purpose of this study was to evaluate the incomplete excision rate of nasal basal cell carcinomas (BCC) resected with different margins to demonstrate that 3-mm surgical margins could be used as safety margins to reduce esthetic consequences with a low risk of incomplete excision. METHODS: All patients with BCC of the nose excised from January 1st 2008 to December 31st 2011 were included. Data were analyzed and reviewed retrospectively. Tumors were treated with different surgical margins of excision: 3mm, 4mm, and 5mm. The primary outcome variable was the rate of incomplete excision. Other study variables were the histologic subtype, size, and recurrent lesions. RESULTS: Of the 132 patients, 115 were included corresponding on with 127 BCC. Median age was 75.5 (64-83) and sex ratio M:F=1.05. Of the 127 BCC, 80 were aggressive histologic subtype (63%), and 11 were recurrent (8.7%). The overall rate of incomplete excision was 17.3% (n=22). Of these 22, 17 (77.3%) were of an aggressive subtype. The incomplete excision rates within the groups were 12.5% (n=4), 22.2% (n=10), and 16% (n=8), respectively within the group with 3-, 4- and 5-mm surgical margins. No significant difference was observed between the groups (P=.519). The incomplete excision rate was not independently associated with the surgical margins, histologic subtype and recurrent type (P>.05). CONCLUSION: Three-millimeters margins could possibly be used to treat nasal BCC in chosen cases. Regarding the high rate of incomplete excision, reconstruction should be performed after receiving the pathologic report. PMID- 26879670 TI - Emerging Network-Based Tools in Movement Ecology. AB - New technologies have vastly increased the available data on animal movement and behaviour. Consequently, new methods deciphering the spatial and temporal interactions between individuals and their environments are vital. Network analyses offer a powerful suite of tools to disentangle the complexity within these dynamic systems, and we review these tools, their application, and how they have generated new ecological and behavioural insights. We suggest that network theory can be used to model and predict the influence of ecological and environmental parameters on animal movement, focusing on spatial and social connectivity, with fundamental implications for conservation. Refining how we construct and randomise spatial networks at different temporal scales will help to establish network theory as a prominent, hypothesis-generating tool in movement ecology. PMID- 26879669 TI - Identification of a prostaglandin D2 metabolite as a neuritogenesis enhancer targeting the TRPV1 ion channel. AB - Mast cells play important roles in allergic inflammation by secreting various mediators. In the present study, based on the finding that the medium conditioned by activated RBL-2H3 mast cells enhanced the nerve growth factor (NGF)-induced neuritogenesis of PC12 cells, we attempted to isolate an active compound from the mast cell conditioned culture medium. Our experiment identified 15-deoxy Delta(12,14)-PGJ2 (15d-PGJ2), one of the PGD2 metabolites, as a potential enhancer of neuritogenesis. 15d-PGJ2 strongly enhanced the neuritogenesis elicited by a low-concentration of NGF that alone was insufficient to induce the neuronal differentiation. This 15d-PGJ2 effect was exerted in a Ca(2+)-dependent manner, but independently of the NGF receptor TrkA. Importantly, 15d-PGJ2 activated the transient receptor potential vanilloid-type 1 (TRPV1), a non selective cation channel, leading to the Ca(2+) influx. In addition, we observed that (i) NGF promoted the insertion of TRPV1 into the cell surface membrane and (ii) 15d-PGJ2 covalently bound to TRPV1. These findings suggest that the NGF/15d PGJ2-induced neuritogenesis may be regulated by two sets of mechanisms, one for the translocation of TRPV1 into the cell surface by NGF and one for the activation of TRPV1 by 15d-PGJ2. Thus, there is most likely a link between allergic inflammation and activation of the neuronal differentiation. PMID- 26879671 TI - Family-Based HIV and Sexually Transmitted Infection Risk Reduction for Drug Involved Young Offenders: 42-Month Outcomes. AB - This study tested a family-based human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention approach integrated within an empirically supported treatment for drug-involved young offenders, Multidimensional Family Therapy (MDFT). A randomized, controlled, two-site community-based trial was conducted with 154 youth and their parents. Drug-involved adolescents were recruited in detention, randomly assigned to either MDFT or Enhanced Services as Usual (ESAU), and assessed at intake, 3, 6, 9, 18, 24, 36, and 42-month follow ups. Youth in both conditions received structured HIV/STI prevention in detention and those in MDFT also received family-based HIV/STI prevention as part of ongoing treatment following detention release. Youth in both conditions and sites significantly reduced rates of unprotected sex acts and STI incidence from intake to 9 months. They remained below baseline levels of STI incidence (10%) over the 42-month follow-up period. At Site A, adolescents who were sexually active at intake and received MDFT showed greater reduction in overall frequency of sexual acts and number of unprotected sexual acts than youth in ESAU between intake and 9-month follow-ups. These intervention differences were evident through the 42 month follow-up. Intervention effects were not found for STI incidence or unprotected sex acts at Site B. Intensive group-based and family intervention in detention and following release may reduce sexual risk among substance-involved young offenders, and a family-based approach may enhance effects among those at highest risk. Site differences in intervention effects, study limitations, clinical implications, and future research directions are discussed. PMID- 26879673 TI - Natural zeolites in diet or litter of broilers. AB - This study aims to analyse the influence of adding natural zeolites (clinoptilolite) to the diet or litter of broilers and their effects on growth performance, carcass yield and litter quality. Three consecutive flocks of broilers were raised on the same sawdust litter, from d 1 to d 42 of age, and distributed in three treatments (control with no added zeolites, addition of 5 g/kg zeolite to diet and addition of 100 g/kg zeolites to litter). The addition of zeolites to the diet or litter did not affect growth performance or carcass yield. The addition of zeolites to the diet did not influence moisture content of the litter, ammonia volatilisation was reduced only in the first flock and pH of litter was reduced in the second and third flock. However, the addition of zeolites to the litter reduced moisture content, litter pH and ammonia volatilisation in all flocks analysed. The addition of 5 g/kg zeolite to the diet in three consecutive flocks was not effective in maintaining litter quality, whereas the addition of 100 g/kg natural zeolites to sawdust litter reduced litter moisture and ammonia volatilisation in three consecutive flocks raised on the same litter. PMID- 26879672 TI - (-)-Epigallocatechin-3-Gallate Enhances Hepatitis C Virus Double-Stranded RNA Intermediates-Triggered Innate Immune Responses in Hepatocytes. AB - (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol component of green tea, has recently been identified as an inhibitor of hepatitis C virus (HCV) entry. Here, we examined whether EGCG can enhance hepatocyte-mediated intracellular innate immunity against HCV. HCV dsRNAs (Core, E1-P7, NS-3'NTR and NS5A) induced interferon-lambda1 (IFN-lambda1) expression in human hepatocytes. These HCV dsRNAs also induced the expression of Toll-like receptor 3 (TLR3), retinoic acid inducible gene I (RIG-I) and several antiviral IFN-stimulated genes (ISGs) expression. Although EGCG treatment of hepatocytes alone had little effect on TLR3 and RIG-I signaling pathways, EGCG significantly enhanced HCV dsRNAs-induced the expression of IFN-lambda1, TLR3, RIG-I and antiviral ISGs in hepatocytes. Furthermore, treatment of HCV-infected hepatocytes with EGCG and HCV dsRNAs inhibited viral replication. Given that EGCG has the ability to enhance HCV dsRNAs-induced intracellular antiviral innate immunity against HCV, suggesting the potential application of EGCG as a new anti-HCV agent for HCV therapy. PMID- 26879674 TI - Morcellation complications: From direct trauma to inoculation. AB - Morcellation is the fragmentation of tissue to facilitate removal of the specimen through small incision in minimally invasive surgery. This technique is not unique to gynecology and is used in general surgery with the goal of improved surgical outcomes including decreased pain, cost, hospital length of stay, and rapid return to normal activities and work. Gynecologic laparoscopic power morcellation (LPM) has come under increased scrutiny over the last 2 years due to widespread attention to a known but rare complication, an unanticipated dissemination of malignancy, namely occult uterine leiomyosarcoma. This chapter focuses on complications associated with gynecologic tissue morcellation from inoculation of benign or malignant tissue fragments within the peritoneal cavity and direct trauma from morcellation techniques. We also include a review of the various morcellation techniques from knife to electrical and the use of intraperitoneal specimen containment systems. PMID- 26879677 TI - The Mighty Mitochondria. PMID- 26879675 TI - Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma. AB - BACKGROUND: Because immune responses within the tumor microenvironment are important predictors of tumor biology, correlations of types of tumor infiltrating lymphocytes (TILs) with clinical outcomes were determined in 278 patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Infiltrating levels of CD4 (helper T cells), CD8 (cytotoxic/suppressor T cells), FoxP3 (regulatory T cells), CD68 (myeloid-derived suppressor cells,) and CD1a (Langerhans) cells were measured in tissue microarrays (TMAs). Cox models tested associations with patient outcomes after adjusting for all known prognostic factors. Median follow-up was 36.6 months. RESULTS: Higher CD4 and CD8 TIL levels were associated with improved overall survival (OS; hazard ratio [HR] = 0.77; 95% confidence interval [CI] = 0.65-0.93; p = .005 and HR = 0.77; 95% CI = 0.64 0.94; p = .008, respectively), and relapse-free survival (RFS; p = .03 and .05, respectively). After controlling for prognostic factors, higher CD4 levels predicted improved OS and disease-specific survival (DSS; p = .003 and p = .004, respectively). CONCLUSION: The findings suggest that TILs are a significant independent prognostic factor for HNSCC that differ by treatment. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1074-1084, 2016. PMID- 26879676 TI - Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease. AB - Hirschsprung disease (HSCR) is attributed to a failure of neural crest derived cells to migrate, proliferate, differentiate or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. This process requires a wide and complex variety of molecules and signaling pathways which are activated by transcription factors. In an effort to better understand the etiology of HSCR, we have designed a study to identify new transcription factors participating in different stages of the colonization process. A differential expression study has been performed on a set of transcription factors using Neurosphere-like bodies from both HSCR and control patients. Differential expression levels were found for CDYL, MEIS1, STAT3 and PAX6. A significantly lower expression level for PAX6 in HSCR patients, would suit with the finding of an over-representation of the larger tandem (AC)m(AG)n repeats within the PAX6 promoter in HSCR patients, with the subsequent loss of protein P300 binding. Alternatively, PAX6 is a target for DNMT3B-dependant methylation, a process already proposed as a mechanism with a role in HSCR. Such decrease in PAX6 expression may influence in the proper function of signaling pathways involved in ENS with the confluence of additional genetic factors to the manifestation of HSCR phenotype. PMID- 26879678 TI - Making a Division Apparatus on Mitochondria. AB - Mitochondrial division apparatuses are generally thought to form by oligomerization of Drp1 at pre-determined sites on mitochondria. A recent study by Ji et al. now shows that the Drp1 oligomers on mitochondria move, merge, and mature into a functional division apparatus. PMID- 26879679 TI - Phenotypic and functional alterations of pDCs in lupus-prone mice. AB - Plasmacytoid dendritic cells (pDCs) were considered to be the major IFNalpha source in systemic lupus erythematosus (SLE) but their phenotype and function in different disease status have not been well studied. To study the function and phenotype of pDCs in lupus-prone mice we used 7 strains of lupus-prone mice including NZB/W F1, NZB, NZW, NZM2410, B6.NZM(Sle1/2/3), MRL/lpr and BXSB/Mp mice and C57BL/6 as control mice. Increased spleen pDC numbers were found in most lupus mice compared to C57BL/6 mice. The IFNalpha-producing ability of BM pDCs was similar between lupus and C57BL/6 mice, whereas pDCs from the spleens of NZB/W F1 and NZB mice produced more IFNalpha than pDCs from the spleens of C57BL/6 mice. Furthermore, spleen pDCs from MRL-lpr and NZM2410 mice showed increased responses to Tlr7 and Tlr9, respectively. As the disease progressed, IFN signature were evaluated in both BM and spleen pDC from lupus prone mice and the number of BM pDCs and their ability to produce IFNalpha gradually decreased in lupus-prone mice. In conclusion, pDC are activated alone with disease development and its phenotype and function differ among lupus-prone strains, and these differences may contribute to the development of lupus in these mice. PMID- 26879681 TI - Proportion of collagen type II in the extracellular matrix promotes the differentiation of human adipose-derived mesenchymal stem cells into nucleus pulposus cells. AB - During degeneration process, the catabolism of collagen type II and anabolism of collagen type I in nucleus pulposus (NP) may influence the bioactivity of transplanted cells. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured as a micromass or in a series of gradual proportion hydrogels of a mix of collagen types I and II. Cell proliferation and cytotoxicity were detected using CCK-8 and LDH assays respectively. The expression of differentiation related genes and proteins, including SOX9, aggrecan, collagen type I, and collagen type II, was examined using RT-qPCR and Western blotting. Novel phenotypic genes were also detected by RT-qPCR and western blotting. Alcian blue and dimethylmethylene blue assays were used to investigate sulfate proteoglycan expression, and PI3K/AKT, MAPK/ERK, and Smad signaling pathways were examined by Western blotting. The results showed collagen hydrogels have good biocompatibility, and cell proliferation increased after collagen type II treatment. Expressions of SOX9, aggrecan, and collagen type II were increased in a collagen type II dependent manner. Sulfate proteoglycan synthesis increased in proportion to collagen type II concentration. Only hADMSCs highly expressed NP cell marker KRT19 in collagen type II culture. Additionally, phosphorylated Smad3, which is associated with phosphorylated ERK, was increased after collagen type II-stimulation. The concentration and type of collagen affect hADMSC differentiation into NP cells. Collagen type II significantly ameliorates hADMSC differentiation into NP cells and promotes extracellular matrix synthesis. Therefore, anabolism of collagen type I and catabolism of type II may attenuate the differentiation and biosynthesis of transplanted stem cells. PMID- 26879680 TI - Different Responses of an Invasive Clonal Plant Wedelia trilobata and its Native Congener to Gibberellin: Implications for Biological Invasion. AB - The invasive clonal plant Wedelia trilobata contains higher levels of ent-kaurane diterpenes, which are precursors of gibberellins (GAs), and higher rates of clonal growth than its native congener W. chinensis in invaded habitats. We hypothesized that the higher levels of endogenous GAs facilitate greater ramet growth in W. trilobata compared with W. chinensis. We quantified endogenous levels of GA1+3 in the two species and compared their growth responses to the changes of endogenous and exogenous GA3 by using short-term and long-term hydroponics experiments. After a period of homogeneous cultivation, levels of endogenous GA1+3 were higher in W. trilobata than in W. chinensis. The reduction of endogenous GAs repressed the emergence of adventitious roots and the growth of W. trilobata in the initial cultivation stage, and inhibited its shoot elongation and biomass. Levels of endogenous GA1+3 were positively correlated with the length of shoots and adventitious roots of W. trilobata. Adventitious roots of W. trilobata also emerged earlier and grew faster when treated with exogenous GA3. In contrast, exogenous GA3 treatment inhibited the length of adventitious roots in W. chinensis, and levels of endogenous GA1+3 did not correlate with shoot or adventitious root length. Our study suggests that GAs accelerate the rapid clonal growth of W. trilobata, more than that of its native congener W. chinensis, illustrating the relationship between plant hormones and the clonal growth of invasive plants. These findings are important for understanding the mechanisms associated with the invasiveness of clonal plants and their potential management. PMID- 26879682 TI - Early atherosclerosis aggravates renal microvascular loss and fibrosis in swine renal artery stenosis. AB - Renal function in patients with atherosclerosis and renal artery stenosis (ARAS) deteriorates more frequently than in nonatherosclerotic RAS. We hypothesized that ARAS aggravates stenotic-kidney micro vascular loss compared to RAS. Domestic pigs were randomized to normal, RAS, and ARAS (RAS fed a high-cholesterol diet) groups (n = 7 each). Ten weeks later stenotic-kidney oxygenation, renal blood flow, and glomerular filtration rate (GFR) were evaluated in vivo, and micro vascular density by micro-computed tomography. Blood pressure in both RAS and ARAS was elevated; and stenotic-kidney renal blood flow and GFR similarly decreased. RAS decreased the density of small-size cortical microvessels (<200 MUm), whereas ARAS extended the decrease to medium-sized microvessels (200-300 MUm). Cortical hypoxia and interstitial fibrosis increased in both RAS and ARAS but correlated inversely with micro vascular density only in RAS. Atherosclerosis aggravates loss of stenotic-kidney microvessels, yet additional determinants likely contribute to cortical hypoxia and fibrosis in swine ARAS. PMID- 26879683 TI - Dehydroepiandrosterone plus climen supplementation shows better effects than dehydroepiandrosterone alone on infertility patients with diminished ovarian reserve of low-FSH level undergoing in-vitro fertilization cycles: a randomized controlled trial. AB - BACKGROUND: This study aimed to assess the effect of dehydroepiandrosterone (DHEA) plus climen (estradiol valerate and cyproterone acetate drug combination) on infertility patients with diminished ovarian reserve (DOR) and to determine if the combination of DHEA plus climen is superior to DHEA alone in improving ovarian response. METHODS: A total of 124 women were randomized into the DHEA group (n = 64) and the DHEA plus climen group (n = 60) for 12 weeks before being subjected to in-vitro fertilization (IVF) cycles. To investigate if there is a FSH-related difference on the effect of the addition of climen, the DHEA group and the DHEA plus climen group were further divided into four subgroups according to a basal FSH level cut-off of 10 mIU/ml. We performed a comparison of Day 3 blood samples before and after treatment and IVF outcome parameters, including AMH, FSH, E2, AFC, oocytes retrieved, MII oocyte numbers, embryo numbers and accumulated embryo scores. RESULTS: After 12 weeks of pretreatment, the DHEA plus climen group demonstrated a significantly higher level of AMH (P = 0.001) and a significantly lower level of FSH (P = 0.001) compared with the DHEA group. When the two groups were divided into four subgroups based on the FSH cut-off of 10 mIU/mL, a significant increase of AMH (P = 0.034) was found in the high-FSH DHEA plus climen group, whereas there was no significant difference in the high-FSH DHEA group (P = 0.322). A significantly higher accumulated score of embryos was observed in the low-FSH DHEA plus climen group compared with the low-FSH DHEA group (P = 0.034). CONCLUSIONS: These observations suggest that patients with DOR of a low-FSH level might benefit more from DHEA plus climen supplementation than from DHEA supplementation alone. PMID- 26879685 TI - Quantitative evaluation of local pulmonary distribution of TiO2 in rats following single or multiple intratracheal administrations of TiO2 nanoparticles using X ray fluorescence microscopy. AB - Uneven pulmonary nanoparticle (NP) distribution has been described when using single-dose intratracheal administration tests. Multiple-dose intratracheal administrations with small quantities of NPs are expected to improve the unevenness of each dose. The differences in local pulmonary NP distribution (called microdistribution) between single- and multiple-dose administrations may cause differential pulmonary responses; however, this has not been evaluated. Here, we quantitatively evaluated the pulmonary microdistribution (per mesh: 100 MUm * 100 MUm) of TiO2 in lung sections from rats following one, two, three, or four doses of TiO2 NPs at a same total dosage of 10 mg kg(-1) using X-ray fluorescence microscopy. The results indicate that: (i) multiple-dose administrations show lower variations in TiO2 content (ng mesh(-1) ) for sections of each lobe; (ii) TiO2 appears to be deposited more in the right caudal and accessory lobes located downstream of the administration direction of NP suspensions, and less so in the right middle lobes, irrespective of the number of doses; (iii) there are not prominent differences in the pattern of pulmonary TiO2 microdistribution between rats following single and multiple doses of TiO2 NPs. Additionally, the estimation of pulmonary TiO2 deposition for multiple-dose administrations imply that every dose of TiO2 would be randomly deposited only in part of the fixed 30-50% of lung areas. The evidence suggests that multiple-dose administrations do not offer remarkable advantages over single-dose administration on the pulmonary NP microdistribution, although multiple-dose administrations may reduce variations in the TiO2 content for each lung lobe. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26879686 TI - Diabetes and cancer, common threads and missing links. AB - Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Accruing epidemiological and clinical evidence have suggested that an increased cancer incidence is associated with diabetes as well as certain diabetes risk factors and diabetes medications. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinemia, enhanced inflammation, aberrant metabolic state, endoplasmic reticulum stress, and deregulation of autophagy. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Furthermore, different anti-diabetic medications may modify cancer risk and mortality in patients with diabetes. This Review discusses evidence to support the relationship between diabetes and cancer development as well as the underlying mechanisms. We also discuss the relationship of current diabetes treatments and cancer risk or prognosis. Understanding the mechanisms that connect type 2 diabetes or diabetes treatments to cancer are crucial for establishing the fundamental strategies concerning about primary prevention, early detection and effective therapy against these diseases. PMID- 26879684 TI - The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial. AB - BACKGROUND: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33% of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. METHODS/DESIGN: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65 years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m(2). Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction >= 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. DISCUSSION: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN03267836 . Date of Registration 20/12/2013. PMID- 26879687 TI - STP Best Practices for Evaluating Clinical Pathology in Pharmaceutical Recovery Studies. AB - The Society of Toxicologic Pathology formed a working group in collaboration with the American Society for Veterinary Clinical Pathology to provide recommendations for the appropriate inclusion of clinical pathology evaluation in recovery arms of nonclinical toxicity studies but not on when to perform recovery studies. Evaluation of the recovery of clinical pathology findings is not required routinely but provides useful information on risk assessment in nonclinical toxicity studies and is recommended when the ability of the organ to recover is uncertain. The study design generally requires inclusion of concurrent controls to separate procedure-related changes from test article-related changes, but return of clinical pathology values toward baseline may be sufficient in some cases. Evaluation of either a select or full panel of standard hematology, coagulation, and serum and urine chemistry biomarkers can be scientifically justified. It is also acceptable to redesignate dosing phase animals to the recovery phase or vice versa to optimize data interpretation. Assessment of delayed toxicity during the recovery phase is not required but may be appropriate in development programs with unique concerns. Evaluation of the recovery of clinical pathology data for vaccine development is required and, for efficacy markers, is recommended if it furthers pharmacologic understanding. PMID- 26879689 TI - Fecal Calprotectin: Diagnostic Accuracy of the Immunochromatographic CalFast Assay in a Pediatric Population. AB - BACKGROUND: Fecal calprotectin is a noninvasive marker for bowel diseases and it is high valuable to follow disease activity in Crohn's disease (CD) and ulcerative colitis (UC). In this study, we evaluated the diagnostic performance of the recently introduced immunochromatographic assay CalFast in comparison to the well-known ELISA tests for calprotectin assay to obtain a rapid diagnosis of bowel inflammation in pediatric patients. METHODS: CalFast was tested in parallel to the classic ELISA tests CalPrest and PhiCal (gold standards for the calprotectin determination) on 148 fecal samples from pediatric subjects including 104 healthy subjects, 29 with CD, and 15 with UC. RESULTS: In this study, the sensitivity and specificity of CalFast, CalPrest, and PhiCal were 86.4%, 88.6%, and 93.2% and 86.6%, 74%, and 64.4%, respectively. The area under the curve, obtained from receiver operating characteristic analysis, indicated the lack of significant difference among all the kits used. CONCLUSION: The immunochromatographic assay demonstrated good diagnostic predictive values, comparable to those of the ELISA methods, and may represent a valid alternative in order to save operators' time. The test, in fact, has a short turnaround time and does not need a specific ELISA instrumentation. PMID- 26879690 TI - Changes in psychopathology in schizophrenia patients starting treatment with new generation antipsychotics: therapeutic drug monitoring in a naturalistic treatment setting. AB - Previous studies on the relationship between plasma levels of new-generation antipsychotics (NGAs) and clinical response did not account for inter- and intra individual variability in drug levels. Therefore, the present study calculated the ratio of observed versus expected NGA plasma levels and investigated its relationship with changes in the Positive and Negative Syndrome Scale (PANSS). Data of patients starting monotherapy with a NGA were collected 2, 4, 8, and 12 weeks after initiation of treatment. Next to the assessment of changes in psychopathology (PANSS) the ratio of observed versus expected plasma level was calculated. A total number of 221 ratios were eligible for analysis. About half of them ranged from 0.5-2 and were considered "normal", whereas the others were considered either "too low" or "too high". Psychopathological symptoms improved over the course of treatment, but changes in PANSS from baseline did not correlate significantly with the ratios of observed versus expected plasma levels at any assessment. The lack of linear correlation can be explained by the fact that 92% of the observed NGA plasma levels were at >= 50% of the lower limit of the therapeutic reference range, i.e., within the asymptote of the logistic plasma level-effect relationship. Accordingly, our findings indicate that the great majority of patients were treated with NGA doses that led to optimal plasma levels, based on the clinical impression of the treating psychiatrist only. Thus, calculating the ratio of observed versus expected plasma level may not be necessary in a routine clinical setting. PMID- 26879688 TI - Recommendations from the INHAND Apoptosis/Necrosis Working Group. AB - Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms "single cell necrosis" and "apoptosis" interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are:Use necrosis and apoptosis as separate diagnostic terms.Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.).Use the combined term apoptosis/single cell necrosis whenThere is no requirement or need to split the processes, orWhen the nature of cell death cannot be determined with certainty, orWhen both processes are present together. The diagnosis should be based primarily on the morphological features in H&E stained sections. When needed, additional, special techniques to identify and characterize apoptosis can also be used. PMID- 26879691 TI - Chronic inflammation and autoimmunity as risk factors for the development of chronic myelomonocytic leukemia? AB - In this study, we investigate if chronic inflammation and autoimmunity might be related to the development of chronic myelomonocytic leukemia (CMML). Conducting a case-control study, we included 112 CMML subjects diagnosed at three hematological departments in Denmark between 2003 and 2013. Controls were 231 unmatched chronic lymphatic leukemia (CLL) subjects diagnosed at one of the departments between 2003 and 2012. Subjects with a history of chronic inflammation or autoimmune disorders were retrieved and odds ratios (ORs) calculated. 16.1% of CMML subjects and 6.5% of CLL subjects presented with a history of chronic inflammatory or autoimmune conditions. This was significantly associated with an increased risk of CMML (adjusted OR 3.24, 95% CI: 1.5-7.0). At individual levels, this association was statistically significant for polymyalgia rheumatica and ITP (p values < 0.01 and 0.03, respectively). We found an association of CMML and smoking status (OR 1.42, 95% CI: 1.06-1.90) with more "former smokers" in the CMML group. PMID- 26879692 TI - Enantioselective Rhodium-Catalyzed Dearomative Arylation or Alkenylation of Quinolinium Salts. AB - A highly enantioselective rhodium(I)-catalyzed dearomative arylation or alkenylation of easily available N-alkylquinolinium salts is reported, thus providing an effective and practical approach to the synthesis of dihydroquinolines in up to 99 % ee. This reaction tolerates a wide range of functional groups with respect to both the organic boronic acids and the quinoline starting materials. Moreover, the synthetic utility of this protocol is demonstrated in the formal asymmetric synthesis of bioactive tetrahydroquinoline and the total syntheses of (-)-angustureine and (+)-cuspareine. PMID- 26879693 TI - The effect of blood pressure and cardiac output on the quality of the surgical field and middle cerebral artery blood flow during endoscopic sinus surgery. AB - BACKGROUND: A clear surgical field is critical during endoscopic sinus surgery (ESS). Hypotensive anesthesia and cardiac output (CO) may optimize the surgical field; however, evidence of their effect on bleeding and cerebral blood flow is conflicting. The aim of this study was to evaluate the effect of blood pressure (BP) and CO on intraoperative bleeding and middle cerebral artery blood flow velocity (Vmca ) during ESS. METHODS: This was a prospective randomized controlled trial. Patients undergoing ESS for chronic rhinosinusitis at a tertiary institution in 2013 were randomized to receive BP manipulation using target-controlled noradrenaline infusion during surgery to either their left or right sinuses. The contralateral side in each patient served as control. Bleeding was scored using a 0 to 10 point bleeding assessment scale (BAS, 0-10) and Vmca was measured using transcranial Doppler ultrasonography every 10 minutes or when surgically opportune, and time-matched with BP and CO. Data was analyzed using Bland-Altman methods. RESULTS: A total of 105 time points were collected across a mean arterial pressure (MAP) range of 32 to 118 mmHg. Significant correlations were demonstrated between MAP and Vmca (r = 0.7, p < 0.0001), MAP and BAS (r = 0.50, p < 0.0001), CO and Vmca (r = 0.57, p < 0.0001), and CO and BAS (r = 0.42, p < 0.0001). The best surgical fields were seen at 40 to 59 mmHg MAP. However, MAP below 60 mmHg produced >50% reduction in Vmca in more than 10% of time points. CONCLUSION: Balancing surgical visibility with organ perfusion remains a challenge. The results of this study show that moderate hypotension significantly improves the surgical field; however reducing BP below 60 mmHg may risk cerebral hypoperfusion. PMID- 26879694 TI - Live Cell Imaging of Actin Dynamics in the Filamentous Fungus Aspergillus nidulans. AB - Hyphal cells of filamentous fungi grow at their tips in a method analogous to pollen tube and root hair elongation. This process, generally referred to as tip growth, requires precise regulation of the actin cytoskeleton, and characterizing the various actin structures in these cell types is currently an active area of research. Here, the actin marker Lifeact was used to document actin dynamics in the filamentous fungus Aspergillus nidulans. Contractile double rings were observed at septa, and annular clusters of puncta were seen subtending growing hyphal tips, corresponding to the well-characterized subapical endocytic collar. However, Lifeact also revealed two additional structures. One, an apical array, was dynamic on the face opposite the tip, while a subapical web was dynamic on the apical face and was located several microns behind the growth site. Each was observed turning into the other over time, implying that they could represent different localizations of the same structure, although hyphae with a subapical web grew faster than those exhibiting an apical array. The subapical web has not been documented in any filamentous fungus to date, and is separate from the networks of F-actin seen in other tip-growing organisms surrounding septa or stationary along the plasmalemma. PMID- 26879695 TI - Measurement of daily physical activity using the SenseWear Armband: Compliance, comfort, adverse side effects and usability. AB - Little is known about the acceptability of wearing physical activity-monitoring devices. This study aimed to examine the compliance, comfort, incidence of adverse side effects, and usability when wearing the SenseWear Armband (SWA) for daily physical activity assessment. In a prospective study, 314 participants (252 people with COPD, 36 people with a dust-related respiratory disease and 26 healthy age-matched people) completed a purpose-designed questionnaire following a 7-day period of wearing the SWA. Compliance, comfort levels during the day and night, adverse side effects and ease of using the device were recorded. Non compliance with wearing the SWA over 7 days was 8%. The main reasons for removing the device were adverse side effects and discomfort. The SWA comfort level during the day was rated by 11% of participants as uncomfortable/very uncomfortable, with higher levels of discomfort reported during the night (16%). Nearly half of the participants (46%) experienced at least one adverse skin irritation side effect from wearing the SWA including itchiness, skin irritation and rashes, and/or bruising. Compliance with wearing the SWA for measurement of daily physical activity was found to be good, despite reports of discomfort and a high incidence of adverse side effects. PMID- 26879697 TI - Pemphigus foliaceus induced by topical 5-fluorouracil. PMID- 26879696 TI - Clinical review: Endobronchial valve treatment for emphysema. AB - Breathlessness and impaired quality of life are prominent features in patients with severe emphysema even when conventional methods of treatment are optimal. Lung volume reduction using endobronchial management for emphysema has emerged as a new method to relieve symptoms and improve lung function tests in this group. The endobronchial valves (EBVs) are the most widely used treatment. This article outlines current criteria of patients' selection with literature review and evidence of efficacy. Complications of EBV insertion as well as current shortfalls of this method of treatment are also discussed. PMID- 26879698 TI - Cell cycle kinetics, apoptosis rates and gene expressions of MDR-1, TP53, BCL-2 and BAX in transmissible venereal tumour cells and their association with therapy response. AB - Transmissible venereal tumour (TVT) generally presents different degrees of aggressiveness, which makes them unresponsive to conventional treatment protocols. This implies a progressive alteration of their biological profile. This study aimed to evaluate the cytotoxicity, cell survival, apoptosis and cell cycle alterations in TVT cell cultures subjected to treatment with vincristine. Similarly, it assessed possible implications of MDR-1, TP53, BCL-2, and BAX gene expressions in eight TVT primary cultures for both resistance to chemotherapy and biological behaviour. When comparing TVT cells receiving vincristine to those untreated, a statistical difference related to increased cytotoxicity and decreased survival rates, and alterations in G1 and S cell cycle phases were found but without detectable differences in apoptosis. Increased MDR-1 gene expression was observed after treatment. The groups did not differ statistically in relation to the TP53, BAX and BCL-2 genes. Although preliminary, the findings suggest that such augmented expression is related to tumour malignancy and chemotherapy resistance. PMID- 26879699 TI - Treatment of bone defects: Bone transport or the induced membrane technique? PMID- 26879700 TI - Recombinant mussel proximal thread matrix protein promotes osteoblast cell adhesion and proliferation. AB - BACKGROUND: von Willebrand factor (VWF) is a key load bearing domain for mamalian cell adhesion by binding various macromolecular ligands in extracellular matrix such as, collagens, elastin, and glycosaminoglycans. Interestingly, vWF like domains are also commonly found in load bearing systems of marine organisms such as in underwater adhesive of mussel and sea star, and nacre of marine abalone, and play a critical load bearing function. Recently, Proximal Thread Matrix Protein1 (PTMP1) in mussel composed of two vWF type A like domains has characterized and it is known to bind both mussel collagens and mammalian collagens. RESULTS: Here, we cloned and mass produced a recombinant PTMP1 from E. coli system after switching all the minor codons to the major codons of E. coli. Recombinant PTMP1 has an ability to enhance mouse osteoblast cell adhesion, spreading, and cell proliferation. In addition, PTMP1 showed vWF-like properties as promoting collagen expression as well as binding to collagen type I, subsequently enhanced cell viability. Consequently, we found that recombinant PTMP1 acts as a vWF domain by mediating cell adhesion, spreading, proliferation, and formation of actin cytoskeleton. CONCLUSIONS: This study suggests that both mammalian cell adhesion and marine underwater adhesion exploits a strong vWF collagen interaction for successful wet adhesion. In addition, vWF like domains containing proteins including PTMP1 have a great potential for tissue engineering and the development of biomedical adhesives as a component for extra-cellular matrix. PMID- 26879701 TI - Epidemiology of childhood and adolescent cancer in Bangladesh, 2001-2014. AB - BACKGROUND: Cancer burden among children and adolescents is largely unknown in Bangladesh. This study aims to provide a comprehensive overview on childhood and adolescent cancers and to contribute to the future strategies to deal with these diseases in Bangladesh. METHODS: Data on malignant neoplasms in patients aged less than 20 years diagnosed between 2001 and 2014 (N = 3143) in Bangladesh was collected by the National Institute of Cancer Research and Hospital and ASHIC Foundation. The age pattern and distribution of cancer types were analysed and the incidence rates were calculated. RESULTS: The age-standardised incidence rate was 7.8 per million person-years for children (0-14 years) in the last time period (2011-2014). Retinoblastoma (25%) and leukaemia (18%) were the most common childhood cancers. For adolescents (15-19 years), the age-specific incidence rate was 2.1 per million person-years in the same time period. Most common adolescent cancers were malignant bone tumours (38%), germ cell and gonadal tumours (17%), and epithelial tumours (16%). There were more boys affected (M: F ratio 2.0 in children and 1.4 in adolescents) than girls. CONCLUSION: Cancer incidences were lower than expected most likely due to a low level of awareness about cancer among clinicians and the population, inadequate access to health care, lack of diagnostic equipment and incomplete recording of cases. Improvements on different levels should be made to get a better epidemiologic insight and to detect cancer earlier resulting in a better outcome for affected children and adolescents. PMID- 26879702 TI - The Motor-Scooter Handlebar Syndrome: Right Common Femoral Artery Occlusion Secondary to Blunt Trauma. PMID- 26879703 TI - Cardiac Complications of Methamphetamine Exposures. PMID- 26879704 TI - Embolic Central Retinal Artery Occlusion Detected with Point-of-care Ultrasonography in the Emergency Department. AB - BACKGROUND: Ocular emergencies account for 2-3% of all emergency department (ED) visits. Sonographic evaluation of the eye offers a very useful diagnostic tool in the ED. In the ED setting, ocular ultrasound could identify a retinal detachment, or a massive vitreous hemorrhage, and the training for emergency medicine practitioners is quite easy. CASE REPORT: An 84-year-old woman presented to our ED with a painless acute vision loss in her right eye. Immediate bedside emergency ocular ultrasound was performed, and it showed a retrobulbar hyperechoic material, suggestive of an embolus within the central retinal artery. Fluorescein angiography showed limited and sluggish filling of the retinal arteries after injection of fluorescein, and optical coherence tomography demonstrated a decrease in the reflectivity and thickness of the inner retinal layers. The final diagnosis was embolic central retinal artery occlusion (CRAO). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Among the causes of acute loss of vision, CRAO is associated with systemic vascular disease. The importance of visible retinal emboli has been well documented due to its association with increase in mortality. A rapid evaluation of the central retinal artery could be a simple tool to identify an embolus, and this could lead to a rapid treatment. The evaluation of central retinal artery is a less defined setting in emergency physician bedside ultrasound, but the identification of CRAO could lead to a rapid acceleration in diagnosis and treatment of a potentially life-threatening disease. PMID- 26879705 TI - A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy - CORRIGENDUM. PMID- 26879706 TI - Nitration of Norcorrolatonickel(II): First Observation of a Diatropic Current in a System Comprising a Norcorrole Ring. AB - A one-pot reaction of 5,14-bis(mesityl)-norcorrolatonickel(II) with isoamyl nitrite under mild reaction conditions resulted in the consecutive formation of 3 nitro-, 3,12-dinitro- and 3,16-dinitro-, 3,7,12-trinitro-, and 3,7,12,16 tetranitro-norcorrolatonickel(II) in 50-80% yield. The substituted macrocycles retained their antiaromatic character. The observed regioselectivity of the substitution was analyzed by comparing the relative energies of the DFT energy optimized models of the radical or arenium cationic intermediates that can be formed upon reaction with NO2. The nitrated systems were characterized by high resolution mass spectrometry, NMR and UV/Vis spectroscopy, X-ray diffraction analysis, cyclic voltammetry, and DFT calculations. A significant and systematic cathodic shift of the redox couples was observed to correlate with an increasing number of the NO2 group. A decrease of the LUMO energies in the tri- and tetra nitrated products stabilizes mono- and bis-reduced complexes of these ligands. The reduction takes place on the macrocycle rather than on the metal ion leading to the consecutive formation of stable paramagnetic monoanion radicals and water soluble diamagnetic dianions with an aromatic character, which were revealed by ESR and (1)H NMR measurements, respectively. The electronic structures of the reduced forms were analyzed by extensive TD-DFT calculations. PMID- 26879707 TI - Prevalence of oral Candida colonization in patients with diabetes mellitus. AB - OBJECTIVES OF THE STUDY: We aimed to assess the prevalence of oral Candida colonization in patients with diabetes and its relationship with factors such as Candida species, serum glucose level, and the susceptibility rate of isolated yeasts to antifungals. PATIENTS: Random samples were obtained from 113 patients with type 2 diabetes, 24 patients with type 1 diabetes, and 105 healthy controls. MATERIALS AND METHODS: The samples were taken by swabbing the oral mucosa of patients with diabetes mellitus and healthy individuals. Afterwards the samples were inoculated onto CHROMagar-Candida. The growing colonies were counted, and the isolated yeasts were identified by PCR-RFLP and RapID methods. Various isolated species of Candida were also subjected to susceptibility testing of antibiotic drugs. Blood samples were taken to evaluate glycosylated hemoglobin (HbA1c). RESULTS: Although the Candida carriage rate and density were statistically higher in diabetics than healthy individuals, no direct association was found between having high Candida-burden and glycosylated hemoglobin. The most commonly isolated species in both diabetics and controls was Candida albicans. Of the tested antifungal drugs, the highest rate of resistance was found against itraconazole, followed in frequency by ketoconazole and fluconazole. CONCLUSIONS: This study identified a significant association between the poor glycemic control and the higher prevalence rates of Candida carriage and density in diabetic patients. In addition, a high prevalence of C. dubliniensis in diabetic patients was found, which might be misdiagnosed with its morphologically related species, C. albicans. PMID- 26879708 TI - CdS Nanowires Decorated with Ultrathin MoS2 Nanosheets as an Efficient Photocatalyst for Hydrogen Evolution. AB - CdS nanowires decorated with ultrathin MoS2 nanosheets were synthesized for the first time by ultrasonic exfoliation by using dimethylformamide as the dispersing agent. An excellent hydrogen evolution rate of 1914 MUmol h(-1) (20 mg catalyst) under visible-light irradiation (lambda >= 400 nm, ~ 154 mW cm(-1) ) and an apparent quantum yield of 46.9% at lambda=420 nm were achieved over the MoS2 /CdS composite. The presence of ultrathin MoS2 nanosheets (rich in active edge sites) on the CdS surface promotes the separation of photogenerated charge carriers and facilitates the surface processes of photocatalytic hydrogen evolution. PMID- 26879709 TI - Contact gating at GHz frequency in graphene. AB - The paradigm of graphene transistors is based on the gate modulation of the channel carrier density by means of a local channel gate. This standard architecture is subject to the scaling limit of the channel length and further restrictions due to access and contact resistances impeding the device performance. We propose a novel design, overcoming these issues by implementing additional local gates underneath the contact region which allow a full control of the Klein barrier taking place at the contact edge. In particular, our work demonstrates the GHz operation of transistors driven by independent contact gates. We benchmark the standard channel and novel contact gating and report for the later dynamical transconductance levels at the state of the art. Our finding may find applications in electronics and optoelectronics whenever there is need to control independently the Fermi level and the electrostatic potential of electronic sources or to get rid of cumbersome local channel gates. PMID- 26879710 TI - Defensive activation to (un)predictable interoceptive threat: The NPU respiratory threat test (NPUr). AB - Potentially life-threatening interoceptive sensations easily engage the behavioral defensive system. Resulting fear and anxiety toward interoceptive threat are functionally distinct states that are hypothesized to play a prominent role in the etiology of panic disorder. The present study aimed to investigate whether fear- and anxiety-potentiated startle responses occur to predictable and unpredictable interoceptive threat, respectively. Therefore, we modified the NPU threat test (Schmitz & Grillon, ) and replaced the aversive electrocutaneous stimulus with an aversive interoceptive stimulus (a breathing occlusion, making it briefly impossible to breathe). Healthy participants (N = 48) underwent three instructed conditions. A visual cue signaled the occlusion in the predictable condition (P), whereas another cue was unrelated to the occurrence of the occlusion in the unpredictable condition (U). The safe condition (N) also had a visual cue, but no occlusion. Both fear- and anxiety-potentiated startle blink responses were observed in response to predictable and unpredictable respiratory threat, respectively. The current study presents and validates the NPU respiratory threat test (NPUr) as an ecologically valid paradigm to study both anxiety and fear in response to a panic-relevant interoceptive threat. The paradigm allows future testing of contextual generalization, investigation of different clinical groups, and more explicit comparisons of defensive responding to interoceptive versus exteroceptive threats. PMID- 26879711 TI - Up high and down low: Molecular systematics and insight into the diversification of the ground beetle genus Rhadine LeConte. AB - Rhadine LeConte is a Nearctic genus of flightless ground beetles that is poorly studied despite its relevance to evolutionary studies of subterranean fauna. Adults are notable for their slender and leggy habitus and the wide variety of habitat preferences among species, with several known only from mountaintops while others are restricted to caves or more general subterranean habitats. In central Texas, USA there are several cave endemics relevant to conservation. Here we present the first phylogenetic hypothesis for the overall structure of the genus with an emphasis on the troglobites in central Texas. We infer the phylogeny of Rhadine from ~2.4-kb of aligned nucleotide sites from the nuclear genes, 28S rDNA and CAD, and the mitochondrial gene COI. These data were obtained for 30 species of Rhadine as well as from members of their putative sister group, Tanystoma Motschulsky. Results reveal that Rhadine is polyphyletic, and morphological characters that have been traditionally used to classify the genus into species groups are shown to be convergent in many cases. Rhadine aside from two species of uncertain placement is composed of two major clades, Clades I and II that both include epigean and subterranean species in very unequal proportions. Clade I is primarily composed of subterranean species, and Clade II includes many epigean species and high altitude montane endemics. A clade of troglobitic, cave-restricted species in Texas includes several species of large eyed cave Rhadine. The slender habitus typical of some species [e.g., R. exilis (Barr and Lawrence), R. subterranea (Van Dyke), R. austinica Barr] evolved independently at least three times. Major biogeographic and evolutionary patterns based on these results include: troglobitic species north of the Colorado River in Texas (that also lack lateral pronotal setae) are found to comprise a monophyletic group, beetles in caves south of the Colorado River likely form another monophyletic group, and the "species pairs" of troglobitic Rhadine known to occur in the same caves are not resolved as each other's sister group, suggesting that these caves were colonized independently by more than one lineage of Rhadine. Our divergence time estimates support a Miocene age for the split between Clade I and II Rhadine and indicate that all subterranean Clade I Rhadine began diversifying in the late Miocene-early Pliocene, contemporary with cave formation in the Balcones Escarpment. PMID- 26879712 TI - Sorting out relationships among the grouse and ptarmigan using intron, mitochondrial, and ultra-conserved element sequences. AB - The Holarctic phasianid clade of the grouse and ptarmigan has received substantial attention in areas such as evolution of mating systems, display behavior, and population ecology related to their conservation and management as wild game species. There are multiple molecular phylogenetic studies that focus on grouse and ptarmigan. In spite of this, there is little consensus regarding historical relationships, particularly among genera, which has led to unstable and partial taxonomic revisions. We estimated the phylogeny of all currently recognized species using a combination of novel data from seven nuclear loci (largely intron sequences) and published data from one additional autosomal locus, two W-linked loci, and four mitochondrial regions. To explore relationships among genera and assess paraphyly of one genus more rigorously, we then added over 3000 ultra-conserved element (UCE) loci (over 1.7million bp) gathered using Illumina sequencing. The UCE topology agreed with that of the combined nuclear intron and previously published sequence data with 100% bootstrap support for all relationships. These data strongly support previous studies separating Bonasa from Tetrastes and Dendragapus from Falcipennis. However, the placement of Lagopus differed from previous studies, and we found no support for Falcipennis monophyly. Biogeographic analysis suggests that the ancestors of grouse and ptarmigan were distributed in the New World and subsequently underwent at least four dispersal events between the Old and New Worlds. Divergence time estimates from maternally-inherited and autosomal markers show stark differences across this clade, with divergence time estimates from maternally-inherited markers being nearly half that of the autosomal markers at some nodes, and nearly twice that at other nodes. PMID- 26879713 TI - [Development and applying of the diagnostic techniques in chest computed tomography]. PMID- 26879714 TI - [Clinical analysis of grand glass opacity on CT as the first change of lung infection accompanied by hematologic malignancies]. AB - OBJECTIVE: To evaluate the value of grand glass opacity(GGO) on CT as a diagnostic sign of pulmonary fungal infection. METHODS: The clinical data of 143 patients treated in department of hematology from January 2007 to June 2015 were analyzed retrospectively, and GGO or other attendant signs were observed. RESULTS: The cases of fungal infection secondary to acute leukemia(AL), myelodysplastic syndromes(MDS), non-Hodgkin's lymphoma(NHL), multiple myeloma(MM), Hodgkin's lymphoma(HL) were 83, 23, 18, 10, 9, respectively, including 23 patients with hematopoietic stem cell transplantation.Ninety percent(128/143) of patients with GGO changes was accompanied with the presence of neutropenia.GGO was mostly accompanied by funicular inflammatory infiltrating shadows or nodules.The cases of possible invasive pulmonary fungal infections(IPFI), probable IPFI, proven IPFI, undefined IPFI were 56, 15, 4, 26, respectively.The total effective cases after anti-fungal therapy was 92. CONCLUSIONS: Ground glass opacity as sign of pulmonary infection of CT mostly occurred in neutropenia and is more common in patients with acute leukemia or hematopoietic stem cell transplantation.GGO is a diagnostic sign of pulmonary fungal infection and it's indicating that anti-fungal medicine should be considered. PMID- 26879715 TI - [Clinicoradiologic characteristics of active pulmonary tuberculosis with perilymphatic involvement]. AB - OBJECTIVE: To evaluate the prevalence of perilymphatic involvement and clinicoradiologic characteristics of active pulmonary tuberculosis according to the distribution of micronodules on CT images. METHODS: A total of 124 in patients with active pulmonary tuberculosis in Haihe Clinical College of Tianjin Medical University from September 2013 to March 2015 were enrolled in this study, all patients underwent CT before antituberculosis therapy.A retrospective investigation of CT images focused on the distribution of micronodules, as well as other major CT features of active pulmonary tuberculosis.Clinical and CT findings of the three groups which based on the distribution of micronodules (perilymphatic, centrilobular and mixed) were compared. RESULTS: All patients existed micronodules.Among these patients, the number of the perilymphatic micronodules, interlobular septal thickening, intralobular septal thickening, bronchial or bronchovascular bundle thickening, galaxy or cluster sign, reversed halo sign was 80(64.5%), 83(66.9%), 56(45.2%), 56(45.2%), 17(13.7%) and 4(3.2%), respectively.There were 35, 36 and 45 cases who were classified into the perilymphatic, centrilobular and mixed groups, respectively.Interlobular septal thickening (88.6% vs 38.9%), intralobular septal thickening (97.1% vs 0), bronchial or bronchovascular bundle thickening (74.3% vs 19.4%) and galaxy or cluster sign (37.1% vs 0) in perilymphatic group were higher than those of centrilobular group, consolidation or macronodule (80% vs 100%) and cavitation (42.9% vs 77.8%) in perilymphatic group were lower than those of centrilobular group. Age (32+/-16 vs 41+/-14), the rate of sputum acid-fast bacilli smears staining positive (28.6% vs 58.3%) and sputum culture positive for Mycobacterium tuberculosis (54.3% vs 94.4%) in perilymphatic group were lower than those of centrilobular group. CONCLUSIONS: CT findings representing pulmonary perilymphatic involvement are relatively common in patients with active tuberculosis, galaxy or cluster sign and reversed halo sign are uncommon. The patients with tuberculosis are relatively younger who principally showed pulmonary perilymphatic involvement, and detection of sputum Mycobacterium tuberculosis in these patients is relatively lower. PMID- 26879716 TI - [Diagnostic value of CT pulmonary artery imaging for idiopathic pulmonary artery hypertension]. AB - OBJECTIVE: To evaluate the diagnostic value of CT pulmonary artery (CTPA) imaging with idiopathic pulmonary artery hypertension (IPAH). METHODS: A total of 20 patients with right heart catheterization (RHC) proven IPAH were retrospectively analyzed between January 2012 and November 2015.The imaging was analyzed including pulmonary parenchyma, pulmonary interstitial, mediastinal lymph nodes, pericardium and pleural cavity on the CTPA examination.Cardiovascular parameters were measured in CTPA including right ventricle biggest short axis diameter (RVD), left ventricle biggest short axis diameter (LVD), main pulmonary artery diameter (MPAD), right pulmonary artery diameter (RPAD), left pulmonary artery diameter (LPAD), right low pulmonary artery diameter (RLPAD), ascending aorta diameter (AAD) and descending aorta diameter (DAD), and parameters were calculated including the ratio of the main pulmonary and ascending aorta diameter (rPA), the ratio of the ascending and descending aorta diameter (rAD), the ratio of the right ventricular and left ventricular short axis diameter (RV/LV). The relationship between sex, pulmonary, lymph nodes, pericardium, pleural and pulmonary arrery pressure (PAP) was analyzed by Spearman rank correlation analysis.All the parameters between mild-moderate (4 cases) and severe (16 cases) PAH were analyzed by independent sample t test.PAP of different age (<50 years and>=50 years) groups was analyzed by Pearson correlation analysis. RESULTS: Of 20 cases, 7 cases showed patch exudative change, 5 cases showed"mosaic pattern"inhomogeneous perfusion, 3 cases displayed ill-defined centrilobular nodules, 6 cases manifested mediastinal lymphadenopathy, 10 cases had pericardial effusion including 4 cases of pleural effusion, 4 cases of dilated bronchial artery, 1 cases of secondary right pulmonary artery embolism.When comparing the presence or absence of pleural effusion, these was statistical difference of PAP (r=0.445, P=0.049). LVD, LPAD, RPAD, AAD, DAD and rPA were statistically different between mild-moderate and severe PAH (t values were 3.194, -3.393, 7.771, 10.299, 11.394 and -12.715, respectively, P<0.05). PAP was statistically different between different age groups (r=-0.481, P=0.032). CONCLUSION: CTPA is a very important examination for the diagnosis of IPAH.The changes of lung, mediastinum, percardium, pleural cavity and the cardiovascular parameters can help diognose and evaluate IPAH. PMID- 26879717 TI - [Microsurgical treatment for giant invasive spinal schwannoma assisted by three dimensional navigation]. AB - OBJECTIVE: To summarize the clinical experience of microsurgical treatment for giant invasive spinal schwannoma assisted by three-dimensional navigation. METHODS: A total of 15 cases of giant invasive spinal schwannoma were retrospectively analyzed from 2013 to 2014 in Beijing Jishuitan Hospital.All patients were performed microsurgery assisted by three-dimensional navigation and were followed up for at least 12 months.A modified McCormick Scale was used to assess the patients' neurologic status and change. RESULTS: Four lesions were in the cervical region, 3 in the sacral, 2 each in the cervicothoracic, lumbar and thoracic regions, 1 each in the thoracolumbar and lumbosacral regions.A total of 28 pedicle screws were placed satisfactorily in the 5 patients with spinal instability.No severe complications were encountered.Gross total resection was performed in 13 of the 15 patients, and subtotal resection performed in 2 patients.Satisfactory decompression was achieved in all patients for neural compression.Postoperative clinical symptoms were improved in all patients, and none of the patients showed loosening or displacement of the implants. CONCLUSIONS: Three-dimensional navigation provides great help for neurosurgeons in surgical treatment of giant invasive spinal schwannoma, and it has great potential in raising the intraoperative localization accuracy, reducing operational damage and surgical complications.Total resection is suggested for giant invasive spinal schwannoma; if not, total resection of the intraspinal portion is recommended. PMID- 26879718 TI - [Clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid arthritis]. AB - OBJECTIVE: The research aimed to evaluate the level and clinical significance of serum 25-hydroxyvitamin D in female patients with rheumatoid arthritis (RA). METHODS: Totally 82 untreated RA female patients (RA group) and 32 healthy females (control group) were enrolled.According to the disease activity score in 28 joints (DAS28), patients in RA group were divided into remission stage group (<2.6 scores, 32 cases) and active stage group (>=2.6 scores, 50 cases). The correlations of 25-hydroxyvitamin D (25-(OH)-D) level with related indicators were analyzed. RESULTS: (1)The levels of serum 25-(OH)-D in female RA active stage group were significantly lower than those in control group [(12.5+/-6.3) MUg/L vs (26.6+/-5.3) MUg/L ] (P<0.01). The levels of serum 25-(OH)-D in female RA remission stage group were significantly lower than those in control group [(14.2+/-7.2) MUg/L vs (26.6+/-5.3) MUg/L] (P<0.01). (2)Serum 25-(OH)-D levels were inversely associated with C reactive protein (CRP), erythrocyte sedimentation rate (ESR), DAS28 score (r=-0.575, r=-0.528, r=-0.354, P<0.05) in female RA active stage group, but not in female RA remission stage group (P>0.05). (3)In active stage group, the 25-(OH)-D levels of premenopausal RA patients were negatively correlated with CRP, ESR, DAS28 (r=-0.707, r=-0.625, r= 0.487, P<0.05), but not in postmenopausal RA patients (P>0.05). CONCLUSIONS: The 25-(OH)-D levels in serum are reduced in female patients with RA.Serum 25-(OH)-D level can be a marker to monitor the disease activity in RA premenopausal female patients. PMID- 26879719 TI - [Small-world properties of the brain functional networks in patients with chronic ischemic stroke]. AB - OBJECTIVE: To explore the characteristics of small-world properties of the brain functional networks in patients with chronic ischemic stroke. METHODS: A total of 42 stroke patients and 25 matched healthy volunteers were scanned with BOLD-fMRI and the whole-brain functional networks were constructed.Two sample t-tests were used to evaluate the changes.The properties including Eglobal, Elocal, Lp, Cp, gamma, lambda, sigma. RESULTS: Within 0.1<=sparsity<=0.2, both groups satisfied the small-world properties(sigma>1). However, the Cp and Elocal of stroke group was significantly lower (P<0.05). CONCLUSIONS: The networks in both groups still satisfied the small-world but parts of the properties in patients have changed. The reduced properties including Cp and Elocal.These changes will provide a new perspective for pathophysiological mechanism and also be helpful for understanding this disease. PMID- 26879720 TI - [Influence of diastolic filling pattern on the efficacy of cardiac resynchronization therapy in patients with non-ischemic cardiomyopathy]. AB - OBJECTIVE: To investigate the influence of diastolic filling pattern on the efficacy of cardiac resynchronization therapy (CRT) in patients with non-ischemic cardiomyopathy. METHODS: Between January 2012 and September 2013, 100 patients with non-ischemic cardiomyopathy undergoing CRT were enrolled in the study, and all patients were grouped by the pre-CRT diastolic filling pattern as impaired relaxation, pseudonormalized and restrictive filling. After follow up for 12 months, the New York Heart Association (NYHA) Class and echocardiography were used to assess the efficacy of CRT.The endpoint was rehospitalization for heart failure or cardiac death. Kaplan-Meier survival curves were plotted to assess prognosis. RESULTS: All patients had varying degrees of diastolic dysfunction.Logistic regression analysis indicated that diastolic filling pattern was the independent factor for the response of CRT.(1)The response rate (78.7%) of impaired relaxation group (n=61) was significantly higher than that of the other two groups (P<0.01); postoperative NYHA class, left ventricular ejection fraction (LVEF), fraction shortening (FS), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were significantly improved (all P<0.01). (2)For pseudonormalized group (n=18), at the 3(rd) month, NYHA class decreased from 3.3+/-0.5 to 2.3+/-0.5, LVEF increased from 27%+/-7% to 31%+/-6% (both P<0.01), and FS improved significantly (P<0.05); no significant decrease of LVEDV and LVESV was found. At the 6(th) month, LVEF improved significantly (P<0.01); LVESV was reduced (P<0.05). (3)In restrictive filling group (n=21), CRT brought short-term improvement in NYHA class but did not induce any significant improvement in LVEF, FS, LVESV and LVEDV.At the 6(th) month, there were significant differences in efficacy among the three groups (P<0.05). At the end of follow-up, 5 patients died, and the cumulative endpoint incidence was significantly higher in restrictive filling group (81%) than the other two groups (P<0.05). CONCLUSIONS: In patients with moderate-to-severe heart failure, left ventricular diastolic dysfunction affects the efficacy of CRT, patients with impaired relaxation benefit significantly, pseudonormalized patients take longer to benefit, but patients with restrictive filling do not benefit from CRT. PMID- 26879721 TI - [Use of quantitative electroencephalogram in patients with septic shock]. AB - OBJECTIVE: To observe the quantitative electroencephalogram (qEEG) characteristics of the patients with septic shock in intensive care unit (ICU), and to find the early presence and severity of septic-associated encephalopathy (SAE) in these patients. METHODS: During November 2014 to August 2015, 26 cases with septic shock were included from the ICU of the First Affiliated Hospital, Sun Yat-sen University.During the same period, 14 healthy volunteers were included as control. The brain function instrument was used to monitor the patients by the bed, placing leads as the internationally used 10-20 system, bipolar longitudinal F3-P3, F4-P4 four channels, and then consecutive clips of 5 minutes was chosen, using the average value of the clips, the amplitude integrated electroencephalogram (aEEG), relative frequency band energy, spectrum entropy, relative alpha ariability to carry out statistical analysis.And the qEEG features of septic shock patients with different Glasgow coma scale (GCS) levels were also analyzed. RESULTS: (1) 96% of the patients with septic shock had EEG abnormalities.Alpha frequency band energy, alpha ariability, aEEG amplitude, spectrum entropy decreased significantly (P<0.05=, while the delta frequency band energy significantly increased (P<0.05=. (2) aEEG amplitude decline appeared in 34% of patients with septic shock, and within the septic shock groups, amplitude decreased significantly (P<0.05= in patients with GCS under five. CONCLUSIONS: Patients with septic shock tends to have diffuse inhibition in EEG, and the inhibition degree can reflect cerebral lesion degree; changes of EEG frequency as early warning indicators of brain damage are sensitive, and the decline of amplitude often indicates critical injury. PMID- 26879722 TI - [Analysis of medical cost of atlantoaxial disorders in patients receiving innovated treatment technologies]. AB - OBJECTIVE: To explore the effects of innovated technologies and products on improving outcomes and decreasing medical costs by analyzing a total and subtotal medical costs of patients with atlantoaxial disorders. METHODS: The medical costs of 1 489 patients with atlantoaxial disorders from Peking University Third Hospital from 2005 to 2014, who received innovated technologies and products treatment were retrospectively analyzed and compared.Descriptive analysis and ANOVA were used for statistical analysis, and SPSS 19.0 was used to analyze data. RESULTS: From 2005 to 2014, under the situation of a general increase in medical cost by 327%, the total medical costs were stable for patients who used innovated technologies and products for treatment, fluctuating from 20 851 in 2005 to 20 878 in 2014; however, the cases of operation increased year by year, from 88 in 2005 to 163 in 2014; the average length of stay decreased from 21 in 2005 to 10 in 2014; the total cases of transfusion were 22 from 2005 to 2014; the safety, stability and feasibility of the innovated technologies and products were illustrated through the decrease of average length of stay, the reduction of bleeding and the significance of outcomes. CONCLUSION: It is illustrated that the innovated technologies and products not only decrease patients' suffering and medical costs but also are safe, stable and feasible. PMID- 26879723 TI - [Clinical analysis of ovarian metastasis in patients with Ib stage cervical adenocarcinoma]. AB - OBJECTIVE: To investigate the rate of ovarian metastasis and its related factors in patients with cervical adenocarcinoma, and explore whether the ovary should be reserved or not in cervical adenocarcinoma. METHOD: The clinical data of 111 patients with cervical adenocarcinoma who received extensive total hysterectomy plus pelvic lymph node resection in Sun Yat-sen Memorial Hospital and Quanzhou Women's and Children's Hospital from January 2008 to December 2014 were collected and analyzed by single factor chi(2) test and multivariate logistic regression analysis. RESULTS: The median age of the included 111 cases of cervical adenocarcinoma was 44. Sixty-five of the patients were stage Ib1, while 46 were stage Ib2. The single factor analysis indicated that lymph-vascular space invasion(LSVI), lymph node status, interstitial infiltration depth, parametrial involvement and involvement of cervical body junction were associated with ovarian metastasis. Multivariate analysis indicated that LSVI (HR: 47.01, 95% CI: 2.48-890.03, P=0.010) and lymph node status (HR: 23.58, 95% CI: 1.20-463.21, P=0.038) were independent risk factors for ovarian metastasis. CONCLUSIONS: Ovarian metastasis rate of stage Ib cervical adenocarcinoma is low; patients with age less than or equal to 45 years old, negative LSVI, <1/2 cervical stromal invasion, no lymph node metastasis and no cervical body junction involvement can consider preservation of ovary; but these findings still need to be further confirmed by large randomized controlled trials. PMID- 26879724 TI - [Association of serum uric acid level with amyotrophic lateral sclerosis]. AB - OBJECTIVE: To investigate the association between the serum uric acid (UA) level and amyotrophic lateral sclerosis(ALS). METHODS: The serum UA levels were measured from 164 ALS patients and 164 gender and age matched controls. The serum creatinine (Cr) and blood urea nitrogen (BUN) levels were also measured to reduce the bias caused by possible differences in renal excretion function.The differences of the above indexes were compared between the two groups. RESULTS: The serum UA levels in ALS patients were lower than those in healthy controls ((310+/-88) MUmol/L vs (356+/-78) MUmol/L, P<0.01). The differences were observed in both genders. In a Logistic regression model using ALS as a dependent variable, the serum UA level was significantly associated with ALS. The differences of the serum UA levels in ALS patients stratified by the revised ALS functional rating scale (ALSFRS-R) and the progression rate of ALSFRS-R(DeltaFS) were not statistically significant (P>0.05). CONCLUSIONS: ALS patients are found to have significantly lower serum UA levels than healthy individuals. The serum UA level is not involved in disease severity and progression. PMID- 26879725 TI - [Prevalence and risk factors of mild vision loss in patients with type 2 diabetes in Beixinjing Community of Shanghai]. AB - OBJECTIVE: To investigate the prevalence and risk factors of mild vision loss in adult patients with type 2 diabetes in Beixinjing Community, Shanghai, China. METHODS: A population-based, cross-sectional survey among 2 216 Chinese Han adult patients with type 2 diabetes was conducted from October 2014 to January 2015.Random cluster sampling was used to enroll diabetic patients based on the local Chronic Diseases Prevention and Control System data.The survey was preceded by a pilot study in which operational methods were refined and quality assurance evaluation was carried out.Eligible participants underwent a comprehensive eye examination, including the best corrected visual acuity (BCVA) test using the logarithm of the minimum angle resolution charts.Mild vision loss was defined as BCVA <20/32 to >=20/63 following the International Council of Ophthalmology (ICO) 2002 definitions.The primary causes of visual impairment and blindness were determined.The prevalence and causes of monocular and binocular mild vision loss were investigated.Logistic regression analysis was used to determine the related risk factors of binocular mild vision loss. RESULTS: Among 2 582 patients, 2 216 were examined, and the response rate was 85.8%.Monocular mild vision loss was found in 591 patients with a prevalence rate of 26.7%.Binocular mild vision loss was detected in 650 patients, with a prevalence rate of 29.3%.Totally 1 891 eyes were confirmed as mild vision loss.Diabetic retinopathy (27.3%, 517/1 891) were the second leading cause of mild vision loss, after cataract (31.3%, 591/1 891). Binocular mild vision loss of unknown reasons happened in 201 persons.Old age, female gender, lower educational level, higher glycosylated hemoglobin A1c level and longer duration of diabetes were associated with the prevalence of total binocular mild vision loss and binocular mild vision loss of unknown reasons. CONCLUSION: The prevalence of mild vision loss is higher among adult patients with type 2 diabetes in Beixinjing Community.Intensive glucose control is recommended to prevent and slow mild vision loss in Chinese Han patients with type 2 diabetes. PMID- 26879726 TI - [Effects of Topiramate for atypical antipsychotic-induced body weight gain and metabolic adversities: a systematic review and meta-analysis]. AB - OBJECTIVE: To systematically determine the effectiveness of Topiramate to counteract atypical antipsychotic-induced body weight gain and metabolic adversities in patients with psychiatric disorders. METHODS: A literature search using MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CNKI, CBM and WanFang Data for randomized, open and double-blind, placebo-controlled trials of Topiramate targeting atypical antipsychotic-induced weight gain was performed.Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.2 software. RESULTS: A total of 10 RCTs was included, consisting of 453 subjects. The results of meta analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol: SMD=-0.23 (95%CI: -0.81 0.35), P=0.44); Triglycerides: SMD=-0.28 (95%CI: -0.75-0.19), P=0.24; HDL: SMD= 0.01 (95%CI: -0.52-0.53), P=0.98); LDL: SMD=-0.39 (95%CI: -0.89-0.11), P=0.13). Meanwhile, when compared with placebo, Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia did not show obviously clinical improvement in concomitant Topiramate group. CONCLUSION: Topiramate can prevent and/or treat atypical antipsychotic induced weight gain and glucose disorder, but current evidence does not support the effect of Topiramate in lipid metabolic regulation and the clinical symptoms improvement assessed by PANSS. PMID- 26879727 TI - Understanding the experience of adult daughters caring for an ageing parent, a qualitative study. AB - AIMS AND OBJECTIVES: The objective of this study is to describe how adult daughters experience caring for a frail older parent at home. BACKGROUND: In the near future the ageing of the population will have a major impact on the demand for formal and informal long-term care. Relatives, especially spouses and adult children are the main providers of informal care. DESIGN: Qualitative research methodology was used to study the experience of adult daughters caring for their frail older parents. A phenomenological research perspective was used to better understand the daily experiences of caring for an ageing parent. METHODS: Data were collected using open-ended interviews. Interviews were audio recorded and transcribed verbatim. Data were subject to thematic analysis. RESULTS: Eleven women between 40-70 years of age participated in this study. Inductive coding of the interview data led to four main themes: being a caregiver as a natural process in life, the perception and consequences of caregiving activities, sharing care and finding a good balance between caring for an ageing parent and other responsibilities. Caregiving activities could be divided into visible and invisible activities and generated different feelings. The visible activities were more easily shared with other family members and professionals than the invisible ones. The women who struggled the most and tended to have a higher level of burden were those who experienced less support from their family. CONCLUSIONS: This study provided more insight into the experiences women have when caring for a parent. Supporting family networks that help in both visible and invisible activities may prevent overburden. RELEVANCE TO CLINICAL PRACTICE: Consumer-led care and the active participation of the informal caregiver in the decision-making process for building the care plan need to become more prominent. PMID- 26879728 TI - Strain Imaging: The Emergence of Speckle Tracking Echocardiography into Clinical Pediatric Cardiology. AB - Speckle tracking echocardiography measures myocardial strain and allows for the quantification of regional and global left and right ventricular function. A growing body of literature is supporting its transition from research into clinical practice. This article aims to provide a practical review of strain imaging as it applies to congenital and pediatric heart disease, with the goals of increasing literacy and advocating for greater clinical integration. PMID- 26879729 TI - Mechanochemical Iridium(III)-Catalyzed C-H Bond Amidation of Benzamides with Sulfonyl Azides under Solvent-Free Conditions in a Ball Mill. AB - Mechanochemical conditions have been applied to an iridium(III)-catalyzed C-H bond amidation process for the first time. In the absence of solvent, the mechanochemical activation enables the formation of an iridium species that catalyzes the ortho-selective amidation of benzamides with sulfonyl azides as the nitrogen source. As the reaction proceeds in the absence of organic solvents without external heating and yields the desired products in excellent yields within short reaction times, this method constitutes a powerful, fast, and environmentally benign alternative to the common solvent-based standard approaches. PMID- 26879730 TI - [De-intensified chemoradiation therapy for favorable-risk human papillomavirus associated oropharyngeal squamous cell carcinoma]. PMID- 26879731 TI - The synergistic effect of surface topography and sustained release of TGF-beta1 on myogenic differentiation of human mesenchymal stem cells. AB - A combination of topographical cues and controlled release of biochemical factors is a potential platform in controlling stem cells differentiation. In this study the synergistic effect of nanotopography and sustained release of biofunctional transforming growth factor beta 1 (TGF-beta1) on differentiation of human Wharton's Jelly-derived mesenchymal stem cell (hWJ-derived UC-MSCs) toward myogenic lineage was investigated. In order to achieve a sustained release of TGF beta1, this factor was encapsulated within chitosan nanoparticles. Afterwards the aligned composite mats were fabricated using poly-E-caprolacton (PCL) containing TGF-beta1-loaded chitosan nanoparticles and poly-L-lactic acid (PLLA). The nanofiber topography notably up-regulated the expressions of calponin1 and SM22alpha compared with tissue culture polystyrene (TCP). Moreover, the combination of nanofiber topography and sustained TGF-beta1release resulted in more significant enhancement of SMC marker, in particular smooth muscle alpha actin (ASMA) expression, compared with bolus delivery despite lower amounts of TGF-beta1 (>10 times lower). Additionally, immunofluorescence staining showed that ASMA and desmin were expressed at higher intensity in cells exposed to controlled TGF-beta1 delivery rather than bolus delivery. These results demonstrated the importance of combined effect of topography and drug delivery in directing stem cell fate and the potential of such biofunctional scaffolds for cell transplantation applications in bladder tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1610-1621, 2016. PMID- 26879732 TI - Safety and Efficacy of Retropubic Mid-urethral Sling Placement in Women Who Void With Valsalva. AB - OBJECTIVE: To compare outcomes after retropubic sling (RPS) in women with and without Valsalva voiding. METHODS: Women who underwent RPS for stress incontinence from 2010 to 2014 were identified and their baseline characteristics were examined. Valsalva voiding was defined as abdominal straining throughout voiding on preoperative urodynamics. Sub-analysis of those with Valsalva included a subset with detrusor underactivity on urodynamics. Follow-up was at 1, 3, 6, and 12 months. Primary outcomes were rates of subjective success, revisions, complications, and voiding dysfunction. Secondary measures were Urogenital Distress Inventory (UDI-6) score, Incontinence Impact Questionnaire (IIQ-7) score, post-void residual, and pad use. RESULTS: Subjects (n = 141) analyzed included 75 Valsalva voiders (VV) and 66 non-Valsalva voiders. At baseline, there were no differences in age, race, comorbidity, post-void residual, pad use, UDI 6, or capacity. Postoperatively, there were no differences in rates of passing initial void trial, need for clean intermittent catheterization, revisions, complications, or voiding dysfunction. No differences in pad use, UDI-6, or IIQ-7 were seen at 6 or 12 months. Within VV, no differences between patients with and without detrusor underactivity were seen for any primary or secondary outcomes (all P > .05). CONCLUSION: In patients who void with Valsalva, RPS appears to be safe and effective. Between VV and non-Valsalva voiders, there were no differences in rates of subjective success, revisions, or complications, even in patients with Valsalva voiding without appreciable detrusor contraction. PMID- 26879733 TI - Impact of Detrusor Underactivity on Surgical Outcomes of Laser Prostatectomy: Comparison in Serial 12-Month Follow-Up Outcomes Between Potassium-Titanyl Phosphate Photoselective Vaporization of the Prostate (PVP) and Holmium Laser Enucleation of the Prostate (HoLEP). AB - OBJECTIVE: To evaluate impacts of preoperative detrusor underactivity (DU) on outcomes of photoselective vaporization of the prostate (PVP) or holmium laser enucleation of the prostate (HoLEP) for benign prostatic hyperplasia, and to compare them between the two surgeries. MATERIALS AND METHODS: A total of 1423 men, who underwent PVP (group A) or HoLEP (group B), were categorized into four groups: A1 (239 without DU), A2 (432 with DU), B1 (329 without DU), and B2 (423 with DU). DU was defined as bladder contractility index of <100. Outcomes were assessed at 1, 3, 6, and 12 months postoperatively using International Prostate Symptom Score (IPSS), uroflowmetry, and prostate-specific antigen. Successful outcome was defined as reductions by >=50% of total IPSS at 12 months postoperatively. RESULTS: In all four groups, almost all parameters of IPSS and uroflowmetry improved starting from 1 month. A1 or B1 had greater increases in maximum flow rate than A2 or B2. Decreases of total IPSS in A2 were less than in A1 starting from 1 month after PVP, whereas those in B2 were less than those in B1 as late as 12 months after HoLEP. B2 showed greater improvements in maximum flow rate, subtotal voiding symptom score, bladder voiding efficiency, and total IPSS than A2. In all patients, multivariate regression analysis revealed that the absence of DU, presence of bladder outlet obstruction, and higher baseline total IPSS were independent predictors of successful outcome after surgery, but the type of laser surgery (PVP vs HoLEP) was not. CONCLUSION: Our data suggest that micturition symptoms, maximum flow rate, bladder voiding efficiency, and quality of life improve starting from the early period after PVP or HoLEP, irrespective of DU. However, patients with DU may have less degree of improvement in micturition after PVP or HoLEP than those without DU. PMID- 26879734 TI - The Long-term Disease-specific Mortality of Low-risk Localized Prostate Cancer: A Prospective Population-based Register Study Over Two Decades. AB - OBJECTIVE: To identify prognostic factors, and to estimate the long-term disease specific and annual disease-specific mortality rates of low-risk prostate cancer patients from the early prostate-specific antigen (PSA) era. PATIENTS AND METHODS: We studied data extracted from the Southeast Region Prostate Cancer Register in Sweden, on1300 patients with clinically localized low-risk tumors, T1 2, PSA level <=10 ug/L and Gleason scores 2-6 or World Health Organization Grade 1, diagnosed 1992-2003. The Cox multivariate regression model was used to evaluate factors predicting survival. Prostate cancer death rates per 1000 person years were estimated for 4 consecutive follow-up time periods: 0-5, 5-10, 10-15, and 15+ years after diagnosis. RESULTS: During the follow-up of overall survivors (mean 10.6 years; maximum 21.8 years), 93 patients (7%) died of prostate cancer. Cancer-specific survival was 0.98 (95% confidence interval [CI] 0.97-0.99), 0.95 (95% CI 0.93-0.96), 0.89 (95% CI 0.86-0.91), and 0.84 (95% CI 0.80-0.88), 5, 10, 15, and 20 years after diagnosis. The 5-year increases in cancer-specific mortality were statistically significant (P < .001). Patients with PSA >= 4 ug/L managed initially with watchful waiting and those aged 70 years or older had a significantly higher risk of dying from their prostate cancer. CONCLUSION: The long-term disease-specific mortality of low-risk localized prostate cancer is low, but the annual mortality rate from prostate cancer gradually increases. This indicates that some tumors slowly develop into lethal cancer, particularly in patients 70 years or older with a PSA level >= 4 ug/L. PMID- 26879735 TI - Experienced Open vs Early Robotic-assisted Laparoscopic Radical Prostatectomy: A 10-year Prospective and Retrospective Comparison. AB - OBJECTIVE: To undertake a prospective/retrospective comparison of longer-term oncologic and quality of life outcomes in open radical prostatectomy (ORP) or robotic-assisted laparoscopic radical prostatectomy (RALP) patients. MATERIALS AND METHODS: The clinical progression of ORP and RALP patients who underwent surgery during 2004 was followed over an extended (10 year) period. Pre- and perioperative parameters, oncologic outcomes, recurrence, mortality, and quality of life were compared between surgical modalities. Follow-up time was calculated from the time of surgery to the latest contact. Postoperative quality of life data were obtained from Expanded Prostate Cancer Index Composite survey questionnaires. Recurrence rates, times to recurrence, surgical time, length of stay, hematocrit, follow-up time, and sexual and urinary bother scores were compared between surgical groups. Multivariate analyses were used to predict positive surgical margins and biochemical recurrence. RESULTS: 63 ORP and 116 RALP patients were included (mean age of 60.4 +/- 6.4 and 58.6 +/- 5.8 years; P = .067), with follow-up times of 10.3 and 10.1 years (P = .191). RALP patients had longer operative times (P < .001), shorter hospital stays (P < .001), and higher discharge hematocrits (P < .001). With prostate-specific antigen, Gleason score, and T-stage as covariates, time to recurrence (P = .365) and positive margin rate (P = .230) were not statistically different between groups. Ninety-five percent of RALP patients were continent and 48.0% were potent vs 92.6% and 41.5% of ORP patients (P = .720; .497). Urinary and sexual bother were not significantly different between groups (P = .392; .985). CONCLUSION: Our longer-term follow-up data suggest that ORP and RALP patients have comparable oncologic and quality of life outcomes. PMID- 26879736 TI - Management of Radiation Anterior Prostato-symphyseal Fistulas With Interposition Rectus Abdominis Muscle Flap. AB - OBJECTIVE: To describe a novel, organ-sparing approach for reconstruction of radiation-induced anterior prostato-symphyseal fistulas (PSFs) at our institution over a consecutive 10-year period. MATERIALS AND METHODS: We performed a retrospective review of patients undergoing surgical reconstruction for anterior PSF between January 1, 2006 and October 31, 2015. Patient demographics as well as preoperative, operative, and postoperative data were reviewed, including etiology of fistula, surgical management, and outcomes. RESULTS: A total of 4 patients with anterior PSF underwent organ-sparing reconstruction. All fistulas were the result of previous pelvic radiation. All 4 patients presented with pubic osteomyelitis. Patients underwent pubic symphysis debridement, fistula closure, and placement of an interposition rectus abdominis muscle flap. At a median follow-up of 27 months, 100% of the patients undergoing repair with interposition rectus flap were closed with 1 procedure. CONCLUSION: Radiation-induced PSF can be successfully reconstructed with pubic symphysis debridement and fistula closure using an adjunct rectus abdominis interposition flap, avoiding prostatectomy and urinary diversion. PMID- 26879737 TI - Where There's Smoke, There's Fire: the Effect of Truncated Testimony on Juror Decision-making. AB - In countries that allow child complainants of abuse to present their direct evidence via pre-recorded videotape, the recording is sometimes truncated for relevance or admissibility purposes before it is presented to the jury. In two experiments, we investigated how this practice affects mock jurors' judgments of child credibility and defendant culpability when truncation omitted the child's less plausible allegations. Mock jurors read a transcript of a 6-year-old girl making an abuse allegation against the janitor at her school. Some jurors read this allegation only (truncated version), while others also read either one or two additional - but less plausible - allegations by the same child. Contrary to what we predicted, the presence of these additional allegations did not decrease jurors' belief in the core allegation, nor did it influence their judgments about the child complainant's honesty or cognitive competence. In fact, under at least one condition, reading additional, less plausible allegations made jurors more likely to pronounce the defendant guilty of the core allegation - even when jurors did not believe the additional allegations. This finding stands in stark contrast to prior research on jurors' evaluation of adults' testimony that includes implausible details. Future research in this area will help to elucidate the conditions under which the presentation of truncated testimony may or may not influence juror decision-making. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26879739 TI - Cell contractility arising from topography and shear flow determines human mesenchymal stem cell fate. AB - Extracellular matrix (ECM) of the human Mesenchymal Stem Cells (MSCs) influences intracellular tension and is known to regulate stem cell fate. However, little is known about the physiological conditions in the bone marrow, where external forces such as fluid shear stress, apart from the physical characteristics of the ECM, influence stem cell response. Here, we hypothesize that substrate topography and fluid shear stress alter the cellular contractile forces, influence the genetic expression of the stem cells and hence alter their lineage. When fluid shear stress was applied, human MSCs with higher contractility (seeded on 1 MUm wells) underwent osteogenesis, whereas those with lower contractility (seeded on 2 MUm gratings) remained multipotent. Compared to human MSCs seeded on gratings, those seeded on wells exhibited altered alignment and an increase in the area and number of focal adhesions. When actomyosin contractility was inhibited, human MSCs did not exhibit differentiation, regardless of the topographical feature they were being cultured on. We conclude that the stresses generated by the applied fluid flow impinge on cell contractility to drive the stem cell differentiation via the contractility of the stem cells. PMID- 26879740 TI - Diagnosis and Treatment of Childhood Meningitis Caused by Streptococcus bovis Group. AB - Streptococcus bovis is a rare, but important cause of bacterial meningitis in children. Since its discovery in the early 1970s, the pathogen has undergone multiple taxonomic changes producing four distinct subspecies today, the most prevalent of which is S. gallolyticus subsp pasteurianus in infants and children. While initially reported as sporadic case reports, there is a growing body of literature documenting invasive disease primarily in neonates and infants clinically indistinguishable from group B streptococcus. In this review, I discuss the taxonomic evolution of S. bovis meningitis and its subsequent clinical diagnosis, manifestations and treatment in children. PMID- 26879741 TI - Pyomyositis in Children. AB - Primary pyomyositis in children is prevalent in the tropics and increasingly being recognised from temperate regions. Staphylococcus aureus remains the principle causative organism worldwide, while proportion of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is on rise. Commonly involved groups are around the pelvis and lower limbs. Clinical presentation depends on the stage of disease, most commonly a child presenting with limping with fever. Early diagnosis and management are crucial. The investigation of choice is MRI scan. Appropriate antibiotic treatment should be instituted at the earliest opportunity along with drainage. Majority of patients show excellent and complete recovery with no long-term complications once treatment is started early. A high level of awareness and suspicion of this condition is warranted from all paediatric clinicians. PMID- 26879742 TI - Multifunctional Antioxidants: Regenerable Radical-Trapping and Hydroperoxide Decomposing Ebselenols. AB - Regenerable, multifunctional ebselenol antioxidants were prepared that could quench peroxyl radicals more efficiently than alpha-tocopherol. These compounds act as better mimics of the glutathione peroxidase enzymes than ebselen. Production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in human mononuclear cells was considerably decreased upon exposure to the organoselenium compounds. At a concentration of 25 MUm, the ebselenol derivatives showed minimal toxicity in pre-osteoblast MC3T3 cells. PMID- 26879743 TI - Differences of side branch jailing between left main-left anterior descending artery stenting and left main-left circumflex artery stenting with Nobori biolimus-eluting stent. AB - The aim of this study is to indicate differences of side branch jailing between the left main (LM)-left anterior descending artery (LAD) stenting and the LM-left circumflex artery (LCx) stenting. Thirty-one patients who underwent single stenting using a two-link ten-crowns biolimus-eluting stent (Japanese design of BES, J-BES) and subsequent kissing balloon dilation (KBD) on an LM bifurcation with optical coherence tomography (OCT) were divided into two groups according to the stented vessel. Bifurcation angles were measured by three-dimensional (3D) quantitative coronary analysis. The jailing pattern on a side branch ostium was evaluated by stent-enhanced 3D-OCT. Incomplete stent apposition (ISA) after KBD was compared between the stented vessels. The to-be-stented angle of the LM-LCx stenting (n = 11) was significantly steeper than that of the LM-LAD stenting (n = 20) (132.6 degrees +/- 16.9 degrees vs. 150.7 degrees +/- 10.6 degrees , p < 0.01). The incidence of the free carina type, which has no stent links bridging from a carina, in the LM-LCx stenting was significantly higher than that in the LM-LAD stenting (90.9 vs. 45.0 %, p = 0.02). The percentage of ISA at the bifurcation segment in the LM-LCx stenting was significantly smaller than that in the LM-LAD stenting (4.4 +/- 8.2 vs. 12.7 +/- 9.2 %, p = 0.0003). This study showed, by higher incidence of the favorable configuration, that the LM-LCx stenting achieved a smaller percentage of ISA than the LM-LAD stenting. These insights may help guide LM bifurcation stenting with J-BES. PMID- 26879744 TI - Pediatric trauma at a general hospital in Cali, Colombia. AB - BACKGROUND: Trauma is an important cause of morbidity and mortality in children. Blunt trauma is the most common type and falls and road traffic injuries (RTI) are the most frequent mechanisms. METHODS: Secondary analysis of institutional data included within the Panamerican Society of Trauma Registry (STP-ITSDP). A total of 581 trauma patients younger than 18years, hospitalized between 2012 and 2014, were included. RESULTS: Blunt trauma (BT) (68%) was the most common type, and falls (42.5%) the most common mechanism. Median age was: 14years for penetrating trauma (PT), 8years for BT, and 5.5years for other types of trauma (OT). Of all patients, 8.1% had a Glasgow score<8, 9% had a Glasgow score of 8-13 and 81.1% had a Glasgow score higher than 14. Death occurred in 5.2% of patients: 83.3% as inpatients and 16.7% during initial management in the emergency room (ER). Patients dying in the ER were mostly PT victims, with higher ISS and lower Glasgow scores. CONCLUSIONS: Trauma is an important cause of morbidity and mortality in our pediatric population. Fundacion Valle de Lili (FVL), a referral hospital, receives a high number of trauma patients from southwestern Colombia. Detailed knowledge of epidemiological data will help us to develop rapid response strategies for patients with trauma and to develop prevention and promotion programs. PMID- 26879745 TI - Comparative and phylogenetic analysis of the mitochondrial genomes in basal hymenopterans. AB - The Symphyta is traditionally accepted as a paraphyletic group located in a basal position of the order Hymenoptera. Herein, we conducted a comparative analysis of the mitochondrial genomes in the Symphyta by describing two newly sequenced ones, from Trichiosoma anthracinum, representing the first mitochondrial genome in family Cimbicidae, and Asiemphytus rufocephalus, from family Tenthredinidae. The sequenced lengths of these two mitochondrial genomes were 15,392 and 14,864 bp, respectively. Within the sequenced region, trnC and trnY were rearranged to the upstream of trnI-nad2 in T. anthracinum, while in A. rufocephalus all sequenced genes were arranged in the putative insect ancestral gene arrangement. Rearrangement of the tRNA genes is common in the Symphyta. The rearranged genes are mainly from trnL1 and two tRNA clusters of trnI-trnQ-trnM and trnW-trnC-trnY. The mitochondrial genomes of Symphyta show a biased usage of A and T rather than G and C. Protein-coding genes in Symphyta species show a lower evolutionary rate than those of Apocrita. The Ka/Ks ratios were all less than 1, indicating purifying selection of Symphyta species. Phylogenetic analyses supported the paraphyly and basal position of Symphyta in Hymenoptera. The well-supported phylogenetic relationship in the study is Tenthredinoidea + (Cephoidea + (Orussoidea + Apocrita)). PMID- 26879746 TI - The effectiveness of pre-operative exercise physiotherapy rehabilitation on the outcomes of treatment following anterior cruciate ligament injury: a systematic review. AB - OBJECTIVE: To evaluate the effectiveness of pre-operative exercise physiotherapy rehabilitation on the outcomes of treatment following anterior cruciate ligament injury. METHODS: The following databases were searched: PubMed, Ovid, The Cochrane Library and Web of Science. Studies published between the inception of the databases and December 2015 were sought using appropriate keywords in various combinations. This search was supplemented with a manual search of the references of selected studies. Studies were assessed for methodological quality using the Physiotherapy Evidence Database scale. RESULTS: A total of 500 studies were identified, of which eight studies met the inclusion criteria and were included in the present review. The average Physiotherapy Evidence Database score for the studies included was 5.8, which reflects an overall moderate methodological quality. The eight studies investigated a total of 451 subjects of which 71% ( n=319) were males. The age of the participants in the eight studies ranged from 15 to 57 years. The duration of the intervention in the studies ranged from 3 to 24 weeks. This review found that pre-operative physiotherapy rehabilitation is effective for improving the outcomes of treatment following anterior cruciate ligament injury, including increasing knee-related function and improving muscle strength. However, whilst there was a significant improvement in quality of life from baseline following intervention, no significant difference in quality of life was found between the control and intervention groups. CONCLUSIONS: There is evidence to suggest that pre-operative physiotherapy rehabilitation is beneficial to patients with anterior cruciate ligament injury. PMID- 26879747 TI - Effect of oxygen availability and pH on the furan concentration formed during thermal preservation of plant-based foods. AB - Thermally treated fruit- and vegetable-based foods are important contributors to the furan exposure of children and adults. Furan reduction by adding or removing precursors from the product has proven to be challenging because of major food constituents and interactions involved in the reaction pathways leading to furan formation. Instead of intervening at the precursor level, it might be more feasible to influence these formation pathways by adjusting the matrix properties of the product. As opposed to many previous literature sources, the present study investigated the effects of oxygen availability (normal versus reduced) and pH (acid versus low acid) on the furan formation in a real food system. Different combinations of both matrix properties were prepared in a reconstituted potato puree and subjected to a thermal treatment with a pasteurisation or sterilisation intensity. Irrespective of the addition of the furan precursors ascorbic acid, fructose and fatty acids, a considerable furan reduction was observed for the sterilised purees (F121(10) = 15 min) with either a reduced oxygen availability (0.1-1.8 mg l(-1)) or at pH 3. The effects of both matrix properties were less pronounced in the pasteurised purees (P90(10) = 10 min), because of the lower furan concentrations. Even though the mechanisms of furan reduction for both types of matrix properties could not be fully elucidated, the results showed that lowering the oxygen concentration or pH prior to thermal processing offers a powerful, additional strategy for furan mitigation in thermally treated plant based foods. PMID- 26879748 TI - The Family Diet Study: a cross-sectional study into the associations between diet, food habits and body weight status in Malay families. AB - BACKGROUND: Childhood obesity is becoming more common as Malaysia experiences rapid nutrition transition. Current evidence related to parental influences on child dietary intake and body weight status is limited. The present study aimed to report, among Malay families, the prevalence of energy mis-reporting and dietary relationships within family dyads. METHODS: The cross-sectional Family Diet Study (n = 236) was conducted at five primary schools in central of Peninsular Malaysia. Each family consisted of a Malay child, aged 8-12 years, and their main caregiver(s). Information on socio-demographics, dietary intake and anthropometry were collected. Correlations and regression analyses were used to assess dietary relationships within family dyads. RESULTS: Approximately 29.6% of the children and 75.0% parents were categorised as being overweight or obese. Intakes of nutrients and food groups were below the national recommended targets for majority of children and adults. A large proportion of energy intake mis reporters were identified: mothers (55.5%), fathers (40.2%) and children (40.2%). Children's body mass index (BMI) was positively associated with parental BMI (fathers, r = 0.37; mothers, r = 0.34; P < 0.01). For dietary intakes, moderate to-strong (0.35-0.72) and weak-to-moderate (0.16-0.35) correlations were found between mother-father and child-parent dyads, respectively. Multiple regression revealed that maternal percentage energy from fat (beta = 0.09, P < 0.01) explained 81% of the variation in children's fat intake. CONCLUSIONS: Clear parental dietary relationships, especially child-mother dyads, were found. Despite a significant proportion of families with members who were overweight or obese, the majority reported dietary intakes below recommended levels, distorted by energy mis-reporting. The findings of the present study can inform interventions targeting parent-child relationships to improve family dietary patterns in Malaysia. PMID- 26879749 TI - Phantom limb perception interferes with motor imagery after unilateral upper-limb amputation. AB - A potential contributor to impaired motor imagery in amputees is an alteration of the body schema as a result of the presence of a phantom limb. However, the nature of the relationship between motor imagery and phantom experiences remains unknown. In this study, the influence of phantom limb perception on motor imagery was investigated using a hand mental rotation task by means of behavioral and electrophysiological measures. Compared with healthy controls, significantly prolonged response time for both the intact and missing hand were observed specifically in amputees who perceived a phantom limb during the task but not in amputees without phantom limb perception. Event-related desynchronization of EEG in the beta band (beta-ERD) in central and parietal areas showed an angular disparity specifically in amputees with phantom limb perception, with its source localized in the right inferior parietal lobule. The response time as well as the beta-ERD values were significantly positively correlated with phantom vividness. Our results suggest that phantom limb perception during the task is an important interferential factor for motor imagery after amputation and the interference might be related to a change of the body representation resulting from an unnatural posture of the phantom limb. PMID- 26879750 TI - Behavioral and emotional adverse events of drugs frequently used in the treatment of bipolar disorders: clinical and theoretical implications. AB - BACKGROUND: Behavioral and emotional adverse events induced by drugs commonly prescribed to patients with bipolar disorders are of paramount importance to clinical practice and research. However, no reviews on the topic have been published so far. METHODS: An extensive search was performed. Reports were reviewed if they described behavioral side effects related to pharmacological treatments for bipolar disorders in healthy subjects or patients with different neuropsychiatric disorders. For this review, lithium, antipsychotics, anticonvulsants and selective serotonin reuptake inhibitors were included. RESULTS: Apathy or emotional blunting, diminished sexual desire, and inability to cry were reported to be associated with exposure to selective serotonin reuptake inhibitors. Neuroleptic-induced deficit syndrome/emotional detachment and obsessive-compulsive symptomatology and decision-making modifications. A lithium related amotivational syndrome was also reported in the literature. Furthermore, hypersexuality and obsessive-compulsive symptoms have been noted in subjects treated with lamotrigine. LIMITATIONS: Primary studies on drug-related adverse events are scant so far and most of the data currently available derive from case reports. Moreover, most of the evidence reviewed is based on studies performed on healthy subjects and patients with neuropsychiatric conditions other than bipolar disorders. DISCUSSION: There is a remarkable dearth of data on behavioral adverse events of pharmacological treatment for bipolar disorders. However, the pieces of evidence available at present, though scant and scattered, suggest that different behavioral adverse events may be related to pharmacological treatment for these disorders. The implications of these findings for research and management of patients with mood disorders are discussed. PMID- 26879751 TI - Conformational Dynamics and Allostery in Pyruvate Kinase. AB - Pyruvate kinase catalyzes the final step in glycolysis and is allosterically regulated to control flux through the pathway. Two models are proposed to explain how Escherichia coli pyruvate kinase type 1 is allosterically regulated: the "domain rotation model" suggests that both the domains within the monomer and the monomers within the tetramer reorient with respect to one another; the "rigid body reorientation model" proposes only a reorientation of the monomers within the tetramer causing rigidification of the active site. To test these hypotheses and elucidate the conformational and dynamic changes that drive allostery, we performed time-resolved electrospray ionization mass spectrometry coupled to hydrogen-deuterium exchange studies followed by mutagenic analysis to test the activation mechanism. Global exchange experiments, supported by thermostability studies, demonstrate that fructose 1,6-bisphosphate binding to the allosteric domain causes a shift toward a globally more dynamic ensemble of conformations. Mapping deuterium exchange to peptides within the enzyme highlight site-specific regions with altered conformational dynamics, many of which increase in conformational flexibility. Based upon these and mutagenic studies, we propose an allosteric mechanism whereby the binding of fructose 1,6-bisphosphate destabilizes an alpha-helix that bridges the allosteric and active site domains within the monomeric unit. This destabilizes the beta-strands within the (beta/alpha)8-barrel domain and the linked active site loops that are responsible for substrate binding. Our data are consistent with the domain rotation model but inconsistent with the rigid body reorientation model given the increased flexibility at the interdomain interface, and we can for the first time explain how fructose 1,6-bisphosphate affects the active site. PMID- 26879752 TI - Pneumatic cystolithotripsy versus holmium:yag laser cystolithotripsy in the treatment of pediatric bladder stones: a prospective randomized study. AB - PURPOSE: Holmium:yttrium-aluminum-garnet (Ho:YAG) laser and Pneumatic cystolithotripsy (CL) are the most widely practiced transurethral procedures for treatment of pediatric bladder stones. The aim of our study was to compare the safety and efficacy of Ho:YAG laser CL and pneumatic CL in the treatment of pediatric bladder stones. METHODS: In this prospective randomized study from January 2012 to April 2015, 25 male children with bladder stones <3 cm were consecutively randomized into two treatment groups: group A (pneumatic CL) consisted of 13 patients and group B (Ho:YAG CL) consisted of 12 patients. Operative time, duration of stay and complications were recorded. Patients were followed up prospectively. RESULTS: The mean operative time was significantly lower in group B (25.6 vs. 31.6 min) for stones <1.5 cm (p = 0.040). However, for stones between 1.5 and 3 cm in size, the mean operating times were similar in both the groups (49.4 min in Ho:YAG vs. 44.6 min in pneumatic, p = 0.40). There was no difference in complication rates and hospital stay in both the groups. No major complications were seen in both the groups. CONCLUSIONS: We found that Ho:YAG CL was more effective than pneumatic CL for treating bladder stones smaller than 1.5 cm. PMID- 26879753 TI - Alterations of putaminal shape in de novo Parkinson's disease. AB - INTRODUCTION: Several neuroimaging studies have been carried out to gain insight on the pathological processes that cause PD, but literature findings are inconsistent. The aim of this study was to combine information carried by functional imaging with DA transporter ligands and structural MRI. METHODS: Forty two untreated, de novo-PD patients and 30 control subjects were involved in this study. Patients were divided in subgroups according to the presence of uni- or bilateral reduction of ligand uptake in the putamen, as observed on DA transporter single-photon emission tomography: 12 patients had abnormal uptake in the right putamen and 11 in the left, whereas 19 had bilateral abnormal uptake. Voxel-based morphometry and shape analysis were used to compare healthy subjects to all de novo-PD or to patients with either right or left abnormal uptake. RESULTS: Shape analysis identified significant differences between de novo-PD and controls in putaminal regions. In patients with unilateral abnormal uptake, only the medial surface of the structure was involved. When patients with bilateral uptake reduction were also considered, changes extended from the medial to the lateral surface of putamina. Voxel-based morphometry showed similar results to those detected with shape analysis, but it failed to identify the putaminal subfield involved in patients with asymmetric or symmetric damage on DA transporter single-photon emission tomography. CONCLUSIONS: Shape analysis in de novo-PD patients suggested a progressive medial-to-lateral involvement of the putamina that paralleled an asymmetric-to-bilateral distribution of DA transporter depletion. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26879754 TI - Up-Regulation of microRNA-183 Promotes Cell Proliferation and Invasion in Glioma By Directly Targeting NEFL. AB - Glioblastoma multiforme (GBM) is the most common and lethal type of primary malignant brain tumor. In recent years, increasing reports suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for human cancers, including GBM. The expression and roles of microRNA-183 (miR-183) has been explored in several types of human cancers, including in GBM, and plays important roles in tumor initiation and progression. However, its biological functions in GBM remain largely unknown. In this study, we demonstrated that miR 183 was significantly up-regulated in astrocytoma tissues and glioblastoma cell lines. Introduction of miR-183 mimics into U251 cells could promoted, while its antisense oligos inhibited cell proliferation and invasion. Moreover, we identified neurofilament light polypeptide (NEFL) as a novel target gene of miR 183. The expression levels of NEFL are inversely correlated with that of miR-183 in human astrocytoma clinical specimens. In addition, NEFL-siRNA could significantly attenuate the inhibitory effects of knockdown miR-183 on the proliferation and invasion of U251 cells via mTOR signaling pathway. Overall, This study revealed that miR-183 promotes glioma cell proliferation by targeting NEFL, and also demonstrated that miR-183 could be a potential target for GBM treatment. PMID- 26879756 TI - Erratum to: PINK1 expression increases during brain development and stem cell differentiation, and affects the development of GFAPpositive astrocytes. PMID- 26879755 TI - Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin. AB - Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism. PMID- 26879757 TI - Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells. AB - Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture, and fundamental Golgi re-organization upon cell fate change. PMID- 26879758 TI - Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation. AB - The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma. PMID- 26879760 TI - E-cadherin is required for cranial neural crest migration in Xenopus laevis. AB - The cranial neural crest (CNC) is a highly motile and multipotent embryonic cell population, which migrates directionally on defined routes throughout the embryo, contributing to facial structures including cartilage, bone and ganglia. Cadherin mediated cell-cell adhesion is known to play a crucial role in the directional migration of CNC cells. However, migrating CNC co-express different cadherin subtypes, and their individual roles have yet to be fully explored. In previous studies, the expression of individual cadherin subtypes has been analysed using different methods with varying sensitivities, preventing the direct comparison of expression levels. Here, we provide the first comprehensive and comparative analysis of the expression of six cadherin superfamily members during different phases of CNC cell migration in Xenopus. By applying a quantitative RT-qPCR approach, we can determine the copy number and abundance of each expressed cadherin through different phases of CNC migration. Using this approach, we show for the first time expression of E-cadherin and XB/C-cadherin in CNC cells, adding them as two new members of cadherins co-expressed during CNC migration. Cadherin co-expression during CNC migration in Xenopus, in particular the constant expression of E-cadherin, contradicts the classical epithelial mesenchymal transition (EMT) model postulating a switch in cadherin expression. Loss-of-function experiments further show that E-cadherin is required for proper CNC cell migration in vivo and also for cell protrusion formation in vitro. Knockdown of E-cadherin is not rescued by co-injection of other classical cadherins, pointing to a specific function of E-cadherin in mediating CNC cell migration. Finally, through reconstitution experiments with different E-cadherin deletion mutants in E-cadherin morphant embryos, we demonstrate that the extracellular domain, but not the cytoplasmic domain, of E-cadherin is sufficient to rescue CNC cell migration in vivo. PMID- 26879761 TI - Selectivity between Oxygen and Chlorine Evolution in the Chlor-Alkali and Chlorate Processes. AB - Chlorine gas and sodium chlorate are two base chemicals produced through electrolysis of sodium chloride brine which find uses in many areas of industrial chemistry. Although the industrial production of these chemicals started over 100 years ago, there are still factors that limit the energy efficiencies of the processes. This review focuses on the unwanted production of oxygen gas, which decreases the charge yield by up to 5%. Understanding the factors that control the rate of oxygen production requires understanding of both chemical reactions occurring in the electrolyte, as well as surface reactions occurring on the anodes. The dominant anode material used in chlorate and chlor-alkali production is the dimensionally stable anode (DSA), Ti coated by a mixed oxide of RuO2 and TiO2. Although the selectivity for chlorine evolution on DSA is high, the fundamental reasons for this high selectivity are just now becoming elucidated. This review summarizes the research, since the early 1900s until today, concerning the selectivity between chlorine and oxygen evolution in chlorate and chlor-alkali production. It covers experimental as well as theoretical studies and highlights the relationships between process conditions, electrolyte composition, the material properties of the anode, and the selectivity for oxygen formation. PMID- 26879762 TI - Regulating the expression of CD80/CD86 on dendritic cells to induce immune tolerance after xeno-islet transplantation. AB - BACKGROUND: Antigen present cells (APCs) have been demonstrated to play dual roles in immune tolerance. Recently, compelling evidence indicates that APCs that express CD80, but not CD86 can protect allograft. We investigated whether modulation of CD80 in dendritic cells (DCs) offer protection for xeno-islets. METHODS: In vitro, isolated mature murine DCs received untransfection, transfection with CD86 siRNA or negative control siRNA. The DCs were used in mixed lymphocyte reaction in which rat islets and murine splenocytes were further added. On day 3 of co-culturing, the proliferation of lymphocytes was measured and interleukin (IL)-2, IL-4, IL-10, transforming growth factor beta (TGF-beta), interferon gamma (INF-gamma) and indoleamine 2,3-dioxygenase (IDO) from the supernatants were determined. Islets viability and function were also assessed. In vivo, streptozotocin-induced diabetic mice underwent rat islets transplantation were pre-treated with above DCs. At designated time, xeno-islets were subjected to histopathology, immunohistochemistry, survival time and functional tests. Peripheral blood T lymphocyte profiles were also examined. RESULTS: CD86-silenced-DCs had unchanged expression of CD80 and significantly suppressed the proliferation of lymphocytes. CD86-silenced-DCs simultaneously reduced IL-2 and INF-gamma and increased IL-10, TGF-beta and IDO, while had minimal effect on IL-4. The CD86-silenced-DCs also improved cell viability and function of xeno-islets when compared to untransfection and transfection control groups. In xeno-islets transplanted diabetic mice, transfer of CD86-silenced-DCs resulted in improved histopathology and dramatically prolonged survival time of the islets. These effects were also mirrored by the functional tests. Further analysis revealed that CD86-silenced-DCs had up-regulated levels of CD4(+)CD25(+)T cells in the peripheral blood compared to the other groups. CONCLUSIONS: CD86-silenced-DCs induced immune tolerance of rat xeno-islets in recipient diabetic mice with up-regulated peripheral blood CD4(+)CD25(+)T cells. PMID- 26879763 TI - Integrated Approach for Pain Management in Parkinson Disease. AB - Pain, one of the most frequent nonmotor symptoms of Parkinson disease (PD), is recognized as an important component of the illness that adversely affects patient quality of life. The aims of this review are to summarize the current knowledge on the clinical assessment and to provide a detailed overview of the evidence-based pharmacologic and nonpharmacologic approaches to treating pain. Results of a literature search include studies investigating pain/sensory abnormalities in PD. The effects of levodopa administration, deep brain stimulation (DBS), pallidotomy, spinal cord stimulation, rehabilitation, and complementary/alternative medicine are reviewed critically. PD patients have altered pain and sensory thresholds; levodopa and DBS improve pain and change sensory abnormalities toward normal levels through antinociceptive and/or modulatory effects that remain unknown. A wide range of nonpharmacologic approaches require further investigation. A multidisciplinary approach is fundamental in managing pain syndromes in PD. PMID- 26879764 TI - Prevalence and associated factors for decreased appetite among patients with stable heart failure. AB - AIMS AND OBJECTIVES: To explore the prevalence of decreased appetite and factors associated with appetite among patients with stable heart failure. BACKGROUND: Decreased appetite is an important factor for the development of undernutrition among patients with heart failure, but there are knowledge gaps about prevalence and the factors related to appetite in this patient group. DESIGN: Observational, cross-sectional study. METHODS: A total of 186 patients with mild to severe heart failure were consecutively recruited from three heart failure outpatient clinics. Data were obtained from medical records (heart failure diagnosis, comorbidity and medical treatment) and self-rated questionnaires (demographics, appetite, self perceived health, symptoms of depression and sleep). Blood samples were taken to determine myocardial stress and nutrition status. Heart failure symptoms and cognitive function were assessed by clinical examinations. The Council on Nutrition Appetite Questionnaire was used to assess self-reported appetite. Bivariate correlations and multivariate linear regression analyses were conducted to explore factors associated with appetite. RESULTS: Seventy-one patients (38%) experienced a loss of appetite with a significant risk of developing weight loss. The final multiple regression model showed that age, symptoms of depression, insomnia, cognitive function and pharmacological treatment were associated with appetite, explaining 27% of the total variance. CONCLUSION: In this cross sectional study, a large share of patients with heart failure was affected by decreased appetite, associated with demographic, psychosocial and medical factors. RELEVANCE TO CLINICAL PRACTICE: Loss of appetite is a prevalent problem among patients with heart failure that may lead to undernutrition. Health care professionals should routinely assess appetite and discuss patients' experiences of appetite, nutrition intake and body weight and give appropriate nutritional advice with respect to individual needs. PMID- 26879765 TI - Transient ischemic attack: management in the emergency department and impact of an outpatient neurovascular clinic. AB - OBJECTIVES: 1) To evaluate whether transient ischemic attack (TIA) management in emergency departments (EDs) of the Nova Scotia Capital District Health Authority followed Canadian Best Practice Recommendations, and 2) to assess the impact of being followed up in a dedicated outpatient neurovascular clinic. METHODS: Retrospective chart review of all patients discharged from EDs in our district from January 1, 2011 to December 31, 2012 with a diagnosis of TIA. Cox proportional hazards models, Kaplan-Meier survival curve, and propensity matched analyses were used to evaluate 90-day mortality and readmission. RESULTS: Of the 686 patients seen in the ED for TIA, 88.3% received computed tomography (CT) scanning, 86.3% received an electrocardiogram (ECG), 35% received vascular imaging within 24 hours of triage, 36% were seen in a neurovascular clinic, and 4.2% experienced stroke, myocardial infarction, or vascular death within 90 days. Rates of antithrombotic use were increased in patients seen in a neurovascular clinic compared to those who were not (94% v. 86.3%, p<0.0001). After adjustment for age, sex, vascular disease risk factors, and stroke symptoms, the risk of readmission for stroke, myocardial infarction, or vascular death was lower for those seen in a neurovascular clinic compared to those who were not (adjusted hazard ratio 0.28; 95% confidence interval 0.08-0.99, p=0.048). CONCLUSION: The majority of patients in our study were treated with antithrombotic agents in the ED and investigated with CT and ECG within 24 hours; however, vascular imaging and neurovascular clinic follow-up were underutilized. For those with neurovascular clinic follow-up, there was an association with reduced risk of subsequent stroke, myocardial infarction, or vascular death. PMID- 26879766 TI - Exploring Regioselective Bond Cleavage and Cross-Coupling Reactions using a Low Valent Nickel Complex. AB - Recently, esters have received much attention as transmetalation partners for cross-coupling reactions. Herein, we report a systematic study of the reactivity of a series of esters and thioesters with [{(dtbpe)Ni}2(MU-eta(2):eta(2)-C6H6)] (dtbpe=1,2-bis(di-tert-butyl)phosphinoethane), which is a source of (dtbpe)nickel(0). Trifluoromethylthioesters were found to form eta(2)-carbonyl complexes. In contrast, acetylthioesters underwent rapid Cacyl-S bond cleavage followed by decarbonylation to generate methylnickel complexes. This decarbonylation could be pushed backwards by the addition of CO, allowing for regeneration of the thioester. Most of the thioester complexes were found to undergo stoichiometric cross-coupling with phenylboronic acid to yield sulfides. While ethyl trifluoroacetate was also found to form an eta(2)-carbonyl complex, phenyl esters were found to predominantly undergo Caryl-O bond cleavage to yield arylnickel complexes. These could also undergo transmetalation to yield biaryls. Attempts to render the reactions catalytic were hindered by ligand scrambling to yield nickel bis(acetate) complexes, the formation of which was supported by independent syntheses. Finally, 2-naphthyl acetate was also found to undergo clean Caryl-O bond cleavage, and although stoichiometric cross-coupling with phenylboronic acid proceeded with good yield, catalytic turnover has so far proven elusive. PMID- 26879767 TI - An assessment of auditory-guided locomotion in an obstacle circumvention task. AB - This study investigated how effectively audition can be used to guide navigation around an obstacle. Ten blindfolded normally sighted participants navigated around a 0.6 * 2 m obstacle while producing self-generated mouth click sounds. Objective movement performance was measured using a Vicon motion capture system. Performance with full vision without generating sound was used as a baseline for comparison. The obstacle's location was varied randomly from trial to trial: it was either straight ahead or 25 cm to the left or right relative to the participant. Although audition provided sufficient information to detect the obstacle and guide participants around it without collision in the majority of trials, buffer space (clearance between the shoulder and obstacle), overall movement times, and number of velocity corrections were significantly (p < 0.05) greater with auditory guidance than visual guidance. Collisions sometime occurred under auditory guidance, suggesting that audition did not always provide an accurate estimate of the space between the participant and obstacle. Unlike visual guidance, participants did not always walk around the side that afforded the most space during auditory guidance. Mean buffer space was 1.8 times higher under auditory than under visual guidance. Results suggest that sound can be used to generate buffer space when vision is unavailable, allowing navigation around an obstacle without collision in the majority of trials. PMID- 26879768 TI - Tactile stimulation during development alters the neuroanatomical organization of the optic nerve in normal rats. AB - This study was designed to investigate the progressive effect of tactile stimulation in the cytoarchitecture of the optic nerve of normal rats during early postnatal development. We used 36 male pups which were randomly assigned to either the tactile-stimulated group (TS-stimulation for 3 min, once a day, from postnatal day (P) 1 to 32) or the non-tactile-stimulated (NTS) group. Morphological analysis were performed to evaluate the alterations caused by tactile stimulation, and morphometric analysis were carried out to determine whether the observed changes in optic nerve cytoarchitecture were significantly different between groups and at three different ages (P18, P22, and P32), thereby covering the entire progression of development of the optic nerve from its start to its completion. The rats of both groups presented similar increase in body weight. The morphometric analysis revealed no difference in the astrocyte density between age-matched groups; however, the oligodendrocyte density of TS group was higher compared to the NTS at P22, and P32, but not at P18. The optic nerve of TS group showed an increase of blood vessels and a reduction of damage fiber density when compared to the age-matched pups of NTS. Taken together, these findings support the view that tactile stimulation, an enriching experience, can positively affects the neuroanatomy of the brain, modifying its cellular components by progressive morphological and morphometric changes. PMID- 26879769 TI - Gait patterns in children with Developmental Coordination Disorder. AB - Previous research has shown that adults with Developmental Coordination Disorder (DCD) show increased variability of foot placement measures and movement of the centre of mass (CoM) while walking. The current study considered the gait patterns of young and older children with DCD. Fourteen young children with DCD (7-12 years), 15 older children with DCD (12-17 years) and 29 age- and gender matched typically developing children took part. Children were asked to walk up and down a flat 10-m-long pathway for 1 min, while the movement of their feet and trunk was recorded using motion analysis. The gait pattern of children with DCD was characterised by wider steps, elevated variability in the time spent in double support and stride time and greater medio-lateral velocity and acceleration compared to their peers. An elevated variability in medio-lateral acceleration was also seen in the young but not the older children with DCD. In addition, the young children showed a greater variability in velocity and acceleration in all three directions compared to the older children. The data suggest that the high incidence of trips and falls seen in children with DCD may be due to differences in the control of the CoM. PMID- 26879770 TI - Coordination of muscle torques stabilizes upright standing posture: an UCM analysis. AB - The control of upright stance is commonly explained on the basis of the single inverted pendulum model (ankle strategy) or the double inverted pendulum model (combination of ankle and hip strategy). Kinematic analysis using the uncontrolled manifold (UCM) approach suggests, however, that stability in upright standing results from coordinated movement of multiple joints. This is based on evidence that postural sway induces more variance in joint configurations that leave the body position in space invariant than in joint configurations that move the body in space. But does this UCM structure of kinematic variance truly reflect coordination at the level of the neural control strategy or could it result from passive biomechanical factors? To address this question, we applied the UCM approach at the level of muscle torques rather than joint angles. Participants stood on the floor or on a narrow base of support. We estimated torques at the ankle, knee, and hip joints using a model of the body dynamics. We then partitioned the joint torques into contributions from net, motion-dependent, gravitational, and generalized muscle torques. A UCM analysis of the structure of variance of the muscle torque revealed that postural sway induced substantially more variance in directions in muscle torque space that leave the Center of Mass (COM) force invariant than in directions that affect the force acting on the COM. This difference decreased when we decorrelated the muscle torque data by randomizing across time. Our findings show that the UCM structure of variance exists at the level of muscle torques and is thus not merely a by-product of biomechanical coupling. Because muscle torques reflect neural control signals more directly than joint angles do, our results suggest that the control strategy for upright stance involves the task-specific coordination of multiple degrees of freedom. PMID- 26879771 TI - Neural activities in V1 create the bottom-up saliency map of natural scenes. AB - A saliency map is the bottom-up contribution to the deployment of exogenous attention. It, as well as its underlying neural mechanism, is hard to identify because of the influence of top-down signals. A recent study showed that neural activities in V1 could create a bottom-up saliency map (Zhang et al. in Neuron 73(1):183-192, 2012). In this paper, we tested whether their conclusion can generalize to complex natural scenes. In order to avoid top-down influences, each image was presented with a low contrast for only 50 ms and was followed by a high contrast mask, which rendered the whole image invisible to participants (confirmed by a forced-choice test). The Posner cueing paradigm was adopted to measure the spatial cueing effect (i.e., saliency) by an orientation discrimination task. A positive cueing effect was found, and the magnitude of the cueing effect was consistent with the saliency prediction of a computational saliency model. In a following fMRI experiment, we used the same masked natural scenes as stimuli and measured BOLD signals responding to the predicted salient region (relative to the background). We found that the BOLD signal in V1, but not in other cortical areas, could well predict the cueing effect. These results suggest that the bottom-up saliency map of natural scenes could be created in V1, providing further evidence for the V1 saliency theory (Li in Trends Cogn Sci 6(1):9-16, 2002). PMID- 26879772 TI - Near-infrared light (670 nm) reduces MPTP-induced parkinsonism within a broad therapeutic time window. AB - We have shown previously that near-infrared light (NIr), when applied at the same time as a parkinsonian insult (e.g. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP), reduces behavioural deficits and offers neuroprotection. Here, we explored whether the timing of NIr intervention-either before, at the same time or after the MPTP insult-was important. Mice received MPTP injections (total of 50 mg/kg) and, at various stages in relation to these injections, extracranial application of NIr. Locomotor activity was tested with an open-field test, and brains were processed for immunohistochemistry. Our results showed that regardless of when NIr was applied in relation to MPTP insult, behavioural impairment was reduced by a similar magnitude. The beneficial effect of NIr was fast-acting (within minutes) and long-lasting (for several days). There were more dopaminergic cells in the NIr-treated MPTP groups than in the MPTP group; there was no clear indication that a particular combination of NIr treatment and MPTP injection resulted in a higher cell number. In summary, irrespective of whether it was applied before, at the same time as or after MPTP insult, NIr reduced both behavioural and structural measures of damage by a similar magnitude. There was a broad therapeutic time window of NIr application in relation to the stage of toxic insult, and the NIr was fast-acting and long-lasting. PMID- 26879773 TI - Assessment of the Access AMH assay as an automated, high-performance replacement for the AMH Generation II manual ELISA. AB - BACKGROUND: The manual Generation II (Gen II) ELISA method used to measure Anti Mullerian Hormone (AMH) from Beckman Coulter has recently been superseded by a fully automated AMH immunoassay. The aim of this study was to evaluate the performance of the Access AMH assay and directly compare it to the modified Gen II ELISA method. A secondary aim was to verify that the fertile age-related AMH range previously established using the Gen II ELISA could be used to interpret results from the new automated Access assay. METHODS: The precision, stability, linearity, measurement range and detection limits were determined using recombinant AMH and patient serum samples. Different diluents and their effects on AMH concentration were compared. A correlation study was performed on patient samples to compare the Access AMH assay to the ELISA method on the Access2 and DxI800 analysers. The fertile AMH range was verified by comparing the 10th, 50th and 90th percentile values from both methods obtained from 489 natural conception pregnant women. RESULTS: The Access AMH assay showed good performance across the measuring range for both intra-assay (CV 1.41-3.30 %) and inter-assay (CV 3.04 5.76 %) precision and acceptable sample stability. Dilution of the high concentration samples with the recommended diluent resulted in a small but significant downward shift in values. The assay was linear over the range of values recommended by the manufacturer, allowing for accurate reporting within the reported range. The two assay types were highly correlated (R(2) = 0.9822 and 0.9832 for Access2 and DxI800, respectively), and the differences observed between the Access2 and DxI800 analysers were within clinically acceptable ranges, indicating that the methods are interchangeable. Furthermore, we demonstrated that results from the published reference range for the Gen II ELISA correlate with those from the automated Access AMH assay. CONCLUSION: Here, we verified the published performance of the Access AMH assay and showed excellent correlation with the Gen II ELISA method. Moreover, we validated this correlation by confirming that the results from a fertile AMH reference range established using the preceding Gen II ELISA are interchangeable with the new automated Access AMH assay. PMID- 26879774 TI - Correction: Dry shear aligning: a simple and versatile method to smooth and align the surfaces of carbon nanotube thin films. AB - Correction for 'Dry shear aligning: a simple and versatile method to smooth and align the surfaces of carbon nanotube thin films' by D. D. Tune et al., Nanoscale, 2016, DOI: 10.1039/c5nr08784h. PMID- 26879775 TI - Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis. AB - BACKGROUND: Acute kidney injury (AKI) is a serious complication among hospitalized individuals and is closely associated with chronic kidney disease (CKD). METHODS: This retrospective cohort study evaluated the incidences of AKI according to CKD stage at Kochi Medical School hospital during 1981-2011. AKI was defined and staged according to the kidney disease improving global outcomes criteria, using serum creatinine levels. RESULTS: We analyzed data from 122,653 Japanese patients (57,105 men, 46.6 %). The incidence of AKI was 7.8 % (95 % confidence interval 7.7-8.0 %). Compared to non-AKI patients, patients with stage 1-2 AKI were more likely to be men. Patients with stage 1-2 AKI were significantly older than non-AKI or stage 3 AKI patients. The incidences of AKI were 6.7, 5.9, 10.4, 18.4, 30.0, and 48.8 % among individuals with estimated glomerular filtration rates of >=90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m2, respectively; these were significantly different from the incidence for the baseline eGFR. The proportions of inpatients with AKI exhibited step-wise increases with more severe pre-existing reduced kidney function, and the proportions among outpatients exhibited step-wise increases with milder pre existing reduced kidney function. CONCLUSIONS: CKD was a risk factor for AKI, and the incidence of AKI was positively associated with pre-existing reduced kidney function (CKD stage). We also found that the prevalence of AKI at early-stage CKD among outpatients was higher than expected. We suggest that outpatients should be monitored for AKI, given its unexpected incidence in that population. PMID- 26879776 TI - Stereoselectivity and the potential endocrine disrupting activity of di-(2 ethylhexyl)phthalate (DEHP) against human progesterone receptor: a computational perspective. AB - Di-(2-ethylhexyl)phthalate (DEHP) is a phthalate plasticizer and is one of the very common endocrine-disrupting chemicals (EDCs) contaminating our ecosystem. It is used for imparting flexibility to plastics and frequently used in personal and industrial products. Clinical and experimental studies have indicated that exposure to DEHP is associated with developmental abnormalities of the reproductive system particularly of male neonates, endometriosis and miscarriage in women, low sperm counts and lower sperm motility and DNA integrity in men, and placental problems with higher rates of low birth weight, premature birth, and fetal loss in laboratory animals. Binding of DEHP to progesterone receptor (PR) represents a potential mechanism of interference in the reproductive functions. DEHP is a chiralmolecule and is available commercially as a racemic mixture of RR, SS and RS stereoisomers. The ability of individual stereoisomers of DEHP to interfere with the reproductive functions of humans and animals is not known and molecular interactions of DEHP stereoisomers with PR are not available. In the present study, in silico approaches were adopted for molecular simulation studies of the three stereoisomers of DEHP with PR. The study suggested that all three stereoisomers of DEHP have the potential to compete with the normal substrate binding of PR. However, the binding of DEHP to PR was stereoselective with RR stereoisomer of DEHP having the best binding characteristics compared with SS, and RS stereoisomers. It has been suggested that stereoselectivity may be employed for improving the safety of the commercial compounds using pure stereoisomers instead of racemic mixtures. PMID- 26879777 TI - Acute Myocardial Infarction in Adult Congenital Patients with Bodily Isomerism. AB - INTRODUCTION: Children born with congenital malformations of the heart are increasingly surviving into adulthood. This population of patients possesses lesion-specific complication risks while still being at risk for common illnesses. Bodily isomerism or heterotaxy, is a unique clinical entity associated with congenital malformations of the heart which further increases the risk for future cardiovascular complications. We aimed to investigate the frequency of myocardial infarction in adults with bodily isomerism. METHODS: We utilized the 2012 iteration of the Nationwide Inpatient Sample to identify adult inpatient admissions associated with acute myocardial infarction in patients with isomerism. Data regarding demographics, comorbidities and various procedures were collected and compared between those with and without isomerism. RESULTS: A total of 6,907,109 admissions were analyzed with a total of 172,394 admissions being associated with an initial encounter for acute myocardial infarction. The frequency of myocardial infarction did not differ between those with and without isomerism and was roughly 2% in both groups. Similarly, the number of procedures and in-hospital mortality did not differ between the two groups. CONCLUSIONS: The frequency and short-term prognosis of acute myocardial infarction is similar in patients with and without isomerism. PMID- 26879778 TI - The predictability and magnitude of life-history divergence to ecological agents of selection: a meta-analysis in livebearing fishes. AB - Environments causing variation in age-specific mortality - ecological agents of selection - mediate the evolution of reproductive life-history traits. However, the relative magnitude of life-history divergence across selective agents, whether divergence in response to specific selective agents is consistent across taxa and whether it occurs as predicted by theory, remains largely unexplored. We evaluated divergence in offspring size, offspring number, and the trade-off between these traits using a meta-analysis in livebearing fishes (Poeciliidae). Life-history divergence was consistent and predictable to some (predation, hydrogen sulphide) but not all (density, food limitation, salinity) selective agents. In contrast, magnitudes of divergence among selective agents were similar. Finally, there was a negative, asymmetric relationship between offspring number and offspring-size divergence, suggesting greater costs of increasing offspring size than number. Ultimately, these results provide strong evidence for predictable and consistent patterns of reproductive life-history divergence and highlight the importance of comparing phenotypic divergence across species and ecological selective agents. PMID- 26879779 TI - Body mass index predicts perioperative complications following orthopaedic trauma surgery: an ACS-NSQIP analysis. AB - PURPOSE: The impact of obesity on outcomes has been documented extensively in the elective orthopaedic literature, but little is known about the impact of obesity on outcomes following orthopaedic trauma surgery. Utilizing the ACS-NSQIP database, we sought to investigate the relationship between BMI and perioperative complications in orthopaedic trauma patients. METHODS: 53,219 orthopaedic trauma patients were identified using a CPT code search between 2005 and 2013 in the NSQIP database. Patient demographics, and perioperative complications (including minor, major, and total) were collected. Multivariate regression analysis was performed to control for baseline demographics and comorbidities. RESULTS: Compared with patients of normal weight, underweight patients had significantly greater odds of minor [OR 1.12, 95 % CI (1.0, 1.26), p = 0.04], major [OR 1.20, 95 % CI (1.1, 1.3), p = 0.0009], and total complications [OR 1.18, 95 % CI (1.1, 1.3), p = 0.0003]. Morbidly obese patients had significantly greater odds of major [OR 1.22, 95 % CI (1.0, 1.5), p = 0.023] and total complications [OR 1.18, 95 % CI (1.0, 1.4), p = 0.023] compared to normal weight patients. When wound related complications were examined independently, obesity was associated with increased odds of superficial [OR 1.67, 95 % CI (1.3, 2.1), p < 0.0001] and deep wound infection [OR 1.52, 95 % CI (1.075, 2.144), p = 0.018], and morbid obesity was associated with increased odds of wound dehiscence [OR 2.29, 95 % CI (1.1, 4.9), p = 0.034] and deep infection [OR 2.51, 95 % CI (1.6, 3.9), p < 0.0001]. CONCLUSIONS: Morbidly obese patients have significantly greater odds of wound dehiscence, deep wound infection, major complications, and total complications compared to patients of normal weight. Additionally, BMI under 18.5 is associated with increased odds of minor, major, and total perioperative complications. Interventions aimed at decreasing complication rates should be targeted at these high-risk patient populations on both ends of the BMI spectrum. PMID- 26879780 TI - Trauma team activation criteria in managing trauma patients at an emergency room in Thailand. AB - BACKGROUND: Trauma team activation (TTA) criteria were first implemented in the Emergency Department (ED) of Songklanagarind Hospital in 2009 to treat severe trauma patients. PURPOSE: To determine the efficacy of the TTA criteria on the acute trauma care process in the ED and the 28-day mortality rate. METHODS: A 1 year prospective cohort study was conducted at the ED. Trauma patients who were 18 years old and over who met the TTA criteria were enrolled. Demographic data, physiologic parameters, ED length of stay (EDLOS), and the injury severity score (ISS) were recorded. Multiple logistic regression was used to determine the factors affecting 28-day mortality. Institutional review board approval was obtained from the Prince of Songkla University. RESULTS: A total of 80 patients (74 male and 6 female) were eligible with a mean age of 34.3 years old. Shock, penetrating torso injury, and pulse rate >120 beats per minute were the three most common criteria for trauma team consultation. At the ED, 9 patients (11.3 %) were non-survivors, 30 patients (37.5 %) needed immediate operation, and 41 patients (51.2 %) were admitted. All of the arrest patients died (p < 0.0001). The median time of EDLOS was 85 min: 68 min in the non-survivor group and 120 min in the survivor group (p = 0.028). The median ISS was 21.0 (1-75): 25.0 in the non-survivor group and 17.0 in the survivor group. When compared with pilot data prior to TTA implementation, the median time of EDLOS improved from 184 to 85 min and the 28-day mortality rate decreased from 66.7 to 46.3 %. The high ISS was a predictor of death. CONCLUSION: The trauma team activation criteria improved acute trauma care in the ED which was demonstrated by the decreased EDLOS and mortality rate. A high ISS is the sole parameter predicting mortality. PMID- 26879781 TI - ["Consensus" and "individual treatment" of Helicobacter pylori infection]. PMID- 26879782 TI - [Indication for Helicobacter pylori eradication: points to ponder]. PMID- 26879783 TI - [The explanation of Holistic Integrative Medicine in theory]. PMID- 26879784 TI - [Quadruple regimens using domestically manufactured drugs in gastritis and duodenal ulcer patients for Helicobacter pylori eradication: a perspective, multicenter, randomized controlled trial]. AB - OBJECTIVE: To observe the effects and safety of quadruple regimens including domestically manufactured rabeprazole used as first line/initial therapy for Helicobacter pylori(H.pylori) eradication in gastritis and duodenal ulcer patients, and to investigate the effects of extended use of bismuth after the quadruple therapy on eradication of H. pylori. METHODS: From January to August 2013, 430 patients with chronic gastritis or duodenal ulcer who were confirmed as H. pylori positive in gastroscopy for upper gastrointestinal symptoms were enrolled from 12 centers in China for initial treatment using quadruple regimens for H. pylori eradication. The study was a prospective, multicenter, randomized double-blinded double-dummy parallel-controlled clinical trial. The 310 chronic gastritis patients were divided into 2 groups: group A1 was given quadruple regime (rabeprazole+ amoxicillin+ clarithromycin+ bismuth potassium citrate) for 10 days followed by bismuth-placebo for 21 days; group A2 was given the quadruple regimen for 10 days and then bismuth potassium citrate for 21 days. The duodenal ulcer patients were given the quadruple for 10 days, then rabeprazole for 14 days. All the patients took (13)C urea breath test to detect H. pylori 28 days after medicine withdrawal. RESULTS: Altogether 428 cases were enrolled and 404 completed the trial. The total eradication rate in the chronic gastritis patients was 85.1% (262/308, intention-to-treat (ITT)analysis), which was 81.7% (125/153, ITT) in the A1 group and 88.4% (137/155, ITT) in the A2 group; the eradication rate in the duodenal ulcer patients was 85.8% (103/120, ITT). No severe adverse effects were reported. The symptoms (pain, burning sensation, reflux, belching, nausea, and vomiting) improvement status was similar among A1 and A2 groups. CONCLUSIONS: The quadruple regimen using rabeprazole manufactured in China and administered for 10 days as first line/initial therapy in chronic gastritis and duodenal ulcer patients could achieve good H. pylori eradication rate. The extended use of bismuth after 10-day quadruple regimen might further improve the eradication rate. The regimens containing proton-pump inhibitor and bismuth may be well tolerated and safe in clinical application. PMID- 26879785 TI - [Detection of Helicobacter pylori by immunoblot: a multiple-center study]. AB - OBJECTIVE: To evaluate the accuracy and effectiveness of Helicobacter pylori(H.pylori)antibody detection kit (immunoblot) in typing H. pylori strains, and to investigate the relationship between characteristics of H. pylori strains and clinical outcomes. METHODS: A total of 378 patients with upper gastrointestinal symptoms who had received gastroscopy and had pathological results within the period from March to August 2012 were collected from 6 centers in China.In all the patients, H. pylori antibody detection kit was used to detect and type serum H. pylori antibodies.The sensitivity, specificity, and accuracy of immunoblot in diagnosing H. pylori infection were evaluation in comparison to (13)C urea breath test (UBT) as the"gold standard". The results were also compared with those colloidal gold method.The relationship between H. pylori typing and clinical conditions was analyzed. RESULTS: Totally 378 patients were enrolled, in which 257 had H. pylori-positive (13)C UBT results, and 121 were negative.With (13)C UBT as the"gold standard", the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of H. pylori antibodies detection kit(immunoblot)were 97.7%, 86.8%, 94.0%, 94.6%, and 94.2%, respectively; the sensitivity, specificity, positive predictive value, negative predictive value, and concordance rate of colloidal gold method were 84.4%, 92.6%, 96.0%, 73.7%, and 87.0%, respectively.In patients diagnosed as H. pylori-positive by (13)C UBT and immunoblot, 93.0%(53/57) in H. pylori eradication failure patients and 93.8%(182/194)in untreated patients were infected with type I H. pylori as detected by immunoblot, with no statistically significant difference (P=0.764). The type I strains positive rate was 94.2%(65/69), 89.9%(62/69)and 98.2% (55/56) in non-atrophy gastritis, atrophy gastritis, and duodenal ulcer untreated patients, respectively, the positive rate of type I strains higher in duodenal ulcer cases than in gastritis ones, but with no statistically significant difference(P=0.185). CONCLUSIONS: Compared with the"gold standard"(13)C UBT, the accuracy of H. pylori antibody detection kit (immunoblot) and that of colloidal gold method are both fairly high.Different H. pylori strains may have significantly different potential in causing diseases, as typeItrain appeared to be more virulent than type II strain, especially in causing peptic ulcer.There was no obvious difference between eradication failure and untreated patients in terms of positive rate of type I H. pylori strains, hence further study is needed to explore the relationship between type I H. pylori and eradication rates. PMID- 26879786 TI - [Antibiotic resistance of Helicobacter pylori clinical isolates in Hebei Province]. AB - OBJECTIVE: To evaluate the resistance of Helicobacter pylori (H.pylori) clinical isolates to various antibiotics, in order to guide rational drug use in Hebei Province. METHODS: From January 2014 to July 2015, 260 patients with H. pylori infection who had not received eradication treatment were enrolled in Third Hospital of Hebei Medical University. Gastric mucosa biopsy tissue samples were collected from these patients before treatment for isolation and culture of H. pylori. Kirby-Bauer method was used to detect drug-resistance rate of the H. pylori clinical isolates to metronidazole, clarithromycin, amoxicillin, levofloxacin, and furazolidone. RESULTS: A total of 155 H. pylori strains were isolated from tissue samples of the 260 patients (positive rate, 59.6%). The drug resistance rate of H. pylori isolated to metronidazole, clarithromycin, amoxicillin, levofloxacin, and furazolidone was 94.2%(146/155), 21.3%(33/155), 2.6%(4/155), 5.8% (9/155), and 1.9%(3/155), respectively. There was no statistically significant difference in positive culture rate and drug-resistance rate between different sex, age, and disease category(all P>0.05). CONCLUSION: In Hebei Province, the resistance rates of H. pylori to metronidazole and clarithromycin appear to be higher than those to amoxicillin, levofloxacin, and furazolidone. PMID- 26879787 TI - [Risk factors associated with long-term mortality in patients with pulmonary embolism and the predictive value of Charlson comorbidity index]. AB - OBJECTIVE: To explore the risk factors associated with long-term mortality and the predictive value of Charlson comorbidity index (CCI) for long-term mortality in patients with pulmonary embolism (PE). METHODS: A total of 234 patients with confirmed PE from the medical departments of West China Hospital of Sichuan University from January 2010 and December 2012 were enrolled, and these meeting the inclusion criteria were followed-up for 2 years after discharge. The long term mortality was calculated and univariate and multivariate analysis were performed to identify the risk factors associated with long-term mortality of PE. All the patients were assessed the comorbidity burden with the CCI, and survival analysis was used to study its value in predicting long-term mortality in patients with PE. RESULTS: A total of 176 PE patients were finally included in this study, and 53 patients died during the follow-up period, with 2 years' mortality 30.1%. The univariate analysis showed diabetes (P=0.034), malignant neoplasm (P=0.001), chronic lung disease (P=0.035), liver disease (P=0.048), in bed for a long time (P=0.049), inappropriate anticoagulant therapy (P=0.016) were associated with the long-term mortality of PE patients. Among these risk factors, the multivariate analysis revealed malignant neoplasm (OR=9.28, 95%CI: 2.85 31.00, P=0.003), chronic lung disease (OR=2.96, 95%CI: 1.15-7.62, P=0.024), inappropriate anticoagulant therapy (OR=4.08, 95%CI: 1.64-10.20, P=0.003) were the independent risk factors. The median CCI scores for died PE patients during follow-up was higher than that for the survived PE patients ((2(1, 3) vs 1(0, 2), P<0.001); PE patients with one and more comorbidities (CCI>=1) were associated with 2.61-fold increased risk of long-term mortality compared with patients with no comorbidity (CCI=0) (95%CI: 1.14-6.00, P=0.024). The per 1-score increase of CCI was associated with 1.76-fold increased risk of long-term mortality in PE patients (95%CI: 1.04-2.97, P=0.035). Survival analysis showed that the 2-year cumulative survival of PE patients with CCI score>=1 was significant lower than that of patients with CCI=0 (46.7% vs 78.5%, P=0.003). CONCLUSIONS: Malignant neoplasm, chronic lung disease and inappropriate anticoagulant therapy are independent risk factors of long-term mortality in patients with PE. The CCI can predict long-term mortality risk among patients with PE and the risk increases with the increase of comorbidites patients have. PMID- 26879788 TI - [Significance of intraoperative precise management on intracavitary treatment for pulmonary thromboembolism]. AB - OBJECTIVE: To compare cardiac adverse events, clinical outcomes and mid-and-long term effects among massive and sub-massive pulmonary embolism (PE) patients under different periodswho received thrombus fragmentation by pigtail catheter. METHODS: Two groups of patients who receivedthrombusfragmentation bypigtail catheter in different periods were analyzed retrospectively. Group E: 38 cases received therapy from July 2004 to October 2009 with local anesthesia; Group P: 64 cases with general anesthesia from March 2010 to December 2014. All patients were confirmedPEby CT and angiography. Parts of patients with deep vein thrombosis (DVT) received inferior vena cava filter placement 3 days later. The patients were followed up for 6-24 months after discharge. Cardiac adverse events, clinical outcomes during the thrombusfragmentation process, and mid-and long-term effects were compared between the two groups. RESULTS: There were no significant differences in preoperative clinical data betweenthe two groups (P>0.05). Compared with group E, clinical warning events were significantly improved in group P (odds ratio(OR): 1.24, 98.3, 1.45, 2.50; P<0.05). Within group P, there were significant differences inarterial oxygen partial pressure (PaO2) [(98.3+/-8.7)vs(81.3+/-7.1)], mean pulmonary artery pressure (mPAP) [(25.3+/-7.9)vs(37.2+/-7.6)], heart rate (HR) [(94.3+/-7)vs(122+/-9)], airway resistance [(16.7+/-1.6)vs (22.5+/-2.1)] and mean arterial pressure (MAP) [(53.4+/-7)vs(42.5+/-6)] before and after thrombus fragmentationtreatment (P<0.05). The incidence of congestive heart failure and pulmonary arterial hypertension associated with chronic pulmonary thromboembolism (CPEPH) during follow-up were significantly different between group P andgroup E (P<0.05). CONCLUSION: Thrombus fragmentation by pigtail catheter with intraoperativeprecise management under general anesthesia can reduce cardiac adverse events andimprove the mid-and-long-term effects among PE patients. PMID- 26879789 TI - [Effectsof the time interval and the endocrine therapy on the prognosis and consistency of the biological indicatorsin patients with bilateral primary breast cancer]. AB - OBJECTIVE: The study aimed to discuss whether the time interval between bilateral primary breast cancers (BPBC)and the endocrine therapy status after thefirst primary cancer could influence the prognosis and consistency of the biological indicators. METHODS: Clinical data of 133 patients with BPBC in cancer institute and hospital of Tianjin medical university from January 2005 to December 2008 were retrospectively analyzed. The patients were divided into two groups according to the time interval and the endocrine therapy. The consistency of hormone receptor and human epidermal growth factor receptor-2 (HER-2) expression between the bilateral tumors and the prognosis of BPBC in different groups were analyzed. RESULTS: With the extension of time interval, the consistent rate of biological indicators between the bilateral tumorshas decreased.The consistent rate of estrogen receptor (ER)was higher than that of progestin hormone (PR) in each group. When the time interval was six or less months, ER and HER-2 had the consistency and correlation between the two primary cancers(P<=0.05). In patients who did not receiveendocrine therapyafter the first cancer, the consistent rates of the biological indicators were higher and ER had betterconsistency and correlation(P<=0.05). Time interval and endocrine therapy hadno effecton the overall survival of the patients. CONCLUSION: With the extension of the time interval, the consistency of the biological indicators in BPBChas decreased.ER and HER-2 of the bilateral tumorshad a high similarity in patients whose time interval wasno more than 6 months.Endocrine therapy could also affect the consistency of the biological indicators.However, these two factors were not associated with prognosis in patients with BPBC. PMID- 26879791 TI - [Cost and effectiveness analysis of treatments for benign prostatic hyperplasia]. AB - OBJECTIVE: To compare the costs and effectiveness of treatments for benign prostatic hyperplasia (BPH), including pharmaceuticals (finasteride, tamsulosin, combined therapy), transurethral 2 micron laser resection of the prostate and transurethral resection of the prostate (TURP). METHODS: Since July 2007 to June 2009, a total of 790 patients with BPH were prospectively collected in this study, including 390 outpatients with pharmaceuticals who were randomly classified into 3 groups of finasteride, tamsulosin and combined therapy, 140 inpatients with transurethral 2 micron laser resection of the prostate and 260 inpatients with TURP. The costs and effectiveness of each group were compared. RESULTS: Prostate volume of finasteride group was decreased after three months of medication, of tamsulosin group no change, of combined therapy group was decreased after one month of medication. Maximum flow rate (MFR) of three groups was higher after one month of medication. International prostate symptom score (IPSS) and quality of life (QOL) score were decreased after one month of medication and further decreased 3 months, 6 months after the medicine, the difference was statistically significant. The effective rate of three pharmaceutical groups after 6 months of treatment was 84%, 89% and 89%, respectively. The cost of operative group was lower than 5-year cost of pharmaceutical group. CONCLUSIONS: Tamsulosin combined with finasteride is the better pharmaceutical option for BPH patients and the transurethral 2 micron laser resection of the prostate, the cost of which is lower than pharmaceuticals, is a safe and effective surgery. PMID- 26879790 TI - [Efficacy and safety analysis of endovascular aortic repair of abdominal aortic aneurysms in patients over eighty years old]. AB - OBJECTIVE: To evaluate the outcome of the endovascular aortic repair (EVAR) of abdominal aortic aneurysms (AAA) in patients over 80 years old and analyze the factors that influence its long-term curative effect. METHODS: Follow-up visits and analysis were conducted from January 2004 to December 2013 on a total of 96 AAA patients aged over 80 years old who had been treated with EVAR and thus met the inclusion criteria. The primary focus of the study was all-cause mortality and secondary focuses included the rate of intervention-related complications, the rate of secondary interventions and procedural data. The Kaplan-Meier survival curve was used to analyze the long-term survival rate and the cumulative probability of intervention-related complications. The Cox proportional hazards regression model was used to analyze factors that could influence the long-term survival rate. RESULTS: Effective follow-up visits were conducted on 76 patients (79.2%). The patients were tracked for an average of 3.63 years, with the longest follow-up lasting 10.34 years. During the study, 27 deaths occurred and the all cause mortality rate was 28.1%. Furthermore, 8 cases of intervention-related complications (8.3%) were observed, including endoleaks and spinal cord ischemia. A total of 6 secondary interventions were conducted on 6 patients, with the rate of secondary interventions being 6.3%. The five-year cumulative survival rate was 64% (95%CI: 0.53-0.78) and the ten-year cumulative survival rate was 35%(95%CI: 0.15-0.84). The Cox proportional hazards model showed that an ASA classification of III/IV (HR=8.45, 95%CI: 1.26-56.55, P<0.05), smoking (HR=2.08, 95%CI: 0.70 2.63, P<0.05) and cerebrovascular diseases (HR=2.96, 95%CI: 1.06-8.25, P<0.05) could significantly increase the risk of the long-term all-cause mortality of an AAA patient treated with EVAR. While hypertension could significantly decrease the risk (HR=0.25, 95%CI: 0.10-0.66, P<0.05). CONCLUSION: EVAR is safe for senior patients with AAA though personalized preoperative assessment is very important. PMID- 26879792 TI - [Effect of laparoscopic surgery under total intravenous anesthesia on postoperative pregnancy outcomes of heterotopic pregnancies]. AB - OBJECTIVE: To evaluate the effects of laparoscopic surgery under total intravenous anesthesia (TIVA) on outcomes of heterotopic pregnancies which need to receive laparoscopic procedures. METHODS: The data of 108 cases of pregnant women in Center of Reproductive Medicine, Peking University Third Hospital were retrospectively analyzed, and divided into two groups according to whether received surgery. Surgery group : 48 pregnant women after in vitro fertilization embryo transfer (IVF-ET) were diagnosed as heterotopic pregnancies and received laparoscopic procedures under TIVA. CONTROL GROUP: 60 normal pregnant women after IVF-ET. The miscarriage rate, pregnant complications rate, premature birth rate, live birth rate, delivery weeks and cesarean section rate of two groups were compared. Meanwhile, the newborn's weight, male rate, birth defect rate and Apgar score in 1 min and 5 min of the two groups were compared. RESULTS: The miscarriage rate, pregnant complications rate, premature birth rate, cesarean section rate, male rate of surgery group were 14.6%, 16.7%, 4.2%, 82.9%, 51.2% respectively, which were 15.0%, 18.3%, 6.7%, 84.3%, 52.9% in control group respectively. There were no significant difference between the two groups (chi(2)=-0.072, -0.241, -0.569, -0.442, -0.163, P>0.05). The delivery weeks and newborn's weight of surgery group were (38.3+/-1.7)weeks and(3 394.9+/-460.7)g respectively , which were (37.9+/-1.5) weeks and (3 406.3+/-512.6 )g in control group. There were no significant difference between the two groups (t=1.083, 0.111, P>0.05). The 1 min Apgar score and 5 min Apgar score of surgery group were 9.6(9.0-10.0), 10(10-10) scores and were 9.5(9.0-10.0), 10(10-10) scores in control group.There were no significant difference between the two groups (Z= 0.418, 0.000, P>0.05). The live birth rate of two groups were both 100%, and the birth defect rate were both 0. CONCLUSION: Laparoscopic surgery under TIVA has no effect on the outcome of heterotopic pregnancies. PMID- 26879793 TI - [Effects of intrathecal injection PI3K antagonist on inflammatory cytokines in spinal cord of bone cancer pain model in rats]. AB - OBJECTIVE: To investigate the roles of PI3K in bone cancer pain, the present study was performed to demonstrate the changes of pain-related behavior and the production of IL-1beta, IL-6 and TNF-alpha after intrathecal injection of wortmannin (antagonist of PI3K receptors) in rat model. METHODS: A total of 44 SD rats were randomly divided into 4 groups, sham group (group S), sham + wormannin group (group SW), cancer group (group A), cancer + wortmannin group (group AW). Group S and group W were injected with 10 MUl Hank's solution into left tibial medullary cavity; group A and group AW received injections of Walker 256 mammary cancer cells(10 MUl, 2*10 cells/ml) into the same place to establish the model of bone cancer pain. In the meantime intratheacal catheterization was performed between L3 and L4 vertrbra on the rats of every group. Nine days after the operation, group S and group A received a single intratheacal injection of saline (0.9%, 10 MUl), group SW and group AW received intratheacal wortmannin 0.5 MUg/10 MUl. Mechanical withdrawal thresholds were measured on the left hind paw before and every 10 min after intrathecal injection. Then the L4-L6 sections of spinal cord 30 min after injection were collected to determine the expression of IL 1beta, IL-6 and TNF-alpha. RESULTS: At 30 min post-injection, mechanical withdrawal thresholds of groups S, SW, A and AW were (30.1+/-4.3), (31.7+/-1.3), (17.2+/-2.0), (24.8+/-2.3) g respectively at Day 9 postinoculation (F=22.403, P<0.01), the mechanical withdrawal thresholds in group AW increased obviously versus group A. The expressions of TNF-alpha in groups S, SW, A and AW were (84.5+/-6.3), (78.7+/-12.5), (110.5+/-7.3), (57.8+/-4.6) pg/ml. Compared with groups S and W, the expression of TNF-alpha in group A showed a significant upregulation (F=28.119, P<0.01). CONCLUSIONS: An intrathecal injection of wortmannin may alleviate hyperalgesia, and inhibit the up-regulated expression of spinal cord inflammatory cytokines TNF-alpha in rats with bone cancer. PI3K may be involved in the development of bone cancer pain by regulating the expressions of TNF-alpha. PMID- 26879794 TI - [Effects of PM2.5 on phagocytic function of alveolar macrophages in chronic obstructive pulmonary disease mice]. AB - OBJECTIVE: To investigate the effects of fine particulate matter with a mean aerodynamic diameter <=2.5 MUm (PM2.5) collected from Lanzhou city on phagocytic function of alveolar macrophages (AM) in chronic obstructive pulmonary disease (COPD) mice. METHODS: Forty male mice were randomly divided into four groups: healthy group, healthy PM2.5 group, COPD group and COPD PM2.5 group. COPD mice were established by cigarette smoking. PM2.5 (10 mg/kg) collected by air sampler was intratracheally instilled in healthy PM2.5 group and COPD PM2.5 group. Mice were sacrificed after 14 days, and alveolar macrophages (AM) were isolated. Mean fluorescence intensity (MFI) and the positive percent of alveolar macrophages engulfing flurescein isothiocyanate-labeled Escherichia coli (FITC-E.coli) (AM%) were detected by flow cytometry. Total antioxidative capacity (TAC) was measured by O-phenanthroline colorimetry. Malondialdehyde (MDA) was measured by thiobarbiturieacid colorimetry and myeloperoxidase (MPO) was measured by O dianisidine colorimetry. RESULTS: The peak inspiratory flow (PIF), peak expiratory flow (PEF) and dynamic compliance (Cdyn) of COPD group were significantly lower than healthy control group. The pathology of COPD group showed disruption of alveolar septa, formation of emphysema, and that the number of alveoli had a significant reduction. The MFI and AM% in COPD group were significant lower than healthy group (14.1+/-1.7 vs 43.2+/-6.1, 9.2%+/-2.3% vs 69.1%+/-8.3%)(all P<0.01). Comparing to healthy group and COPD group, the MFI and AM% in healthy PM2.5 group (20.3+/-4.5, 40.4%+/-4.4%) and COPD PM2.5 group (7.5+/ 1.3, 6.0%+/-2.2%) were respectively lowered. The level of TAC in COPD group was significantly lower than healthy group [(3.10+/-0.64) vs (15.43+/-0.69)U/mg], the levels of MDA and MPO in COPD group were higher than healthy group[(2.72+/-0.13) vs (1.31+/-0.16) nmol/mg, (1.63+/-0.11) vs (0.92+/-0.13)U/g] (all P<0.01). In both healthy PM2.5 group and COPD PM2.5 group, the levels of TAC [(6.75+/-1.06), (2.34+/-0.61) U/mg] were lower than their corresponding control group; while the levels of MDA [(1.96+/-0.31), (3.20+/-0.19) nmol/mg] and the levels of MPO [(1.01+/-0.19), (1.74+/-0.13) U/g] were increased (all P<0.01). For the COPD group at baseline and after the intervention of PM2.5, the MFI and AM% showed positive correlation with the levels of TAC, and negative correlation with the levels of MDA , and negative correlation with the levels of MPO (all P<0.05). For health group at baseline and after the intervention PM2.5, the above relationships still existed (all P<0.05). CONCLUSION: PM2.5 can damage phagocytosis of AM and exacerbate oxidative stress in COPD mice, and AM phagocytosis impairment by PM2.5 is closely associated with oxidative stress. PMID- 26879795 TI - [Quantitatively evaluating the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment]. AB - OBJECTIVE: To quantitatively evaluate the evolution of the tumor perfusion in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. METHODS: To establish the preclinical transplantation model of lung adenocarcinoma, 60 BALB/c nu/nu mice was inoculated with A549 cell lines via axilla. Sixty mice were randomly divided into 2 groups. The treatment group was treated with intravenous Bevacizumab (10 mg/kg weight, in a single injection), and the control group received saline only in the same dose. Five times of volume perfusion CT (VPCT) scan was performed before treatment, and on the second, forth, sixth and tenth days of treatment, respectively. The values of blood flow (BF) in the A549 tumors were measured after scanning. The microvessel density (MVD), vessel maturity index (VMI) in the tumors were determined using multiplexed QDs-based immunohistochemical staining. RESULTS: Comparing the values of BF, VMI and MVD between the two groups on the same day before treatment, the values of BF, VMI and MVD of the treatment group were (13.5+/-1.5) ml.(100 ml)( 1).min(-1,) 0.14+/-0.04, (45.7+/-16.5)/HPF, respectively, and those in the control group were (13.4+/-1.6) ml.(100 ml)(-1).min(-1) , 0.14+/-0.05, (48.0+/ 7.0) /HPF , respectively. There was no significant difference between the two groups (all P>0.05). And on the second, forth, sixth, tenth days of treatment, the values of BF of the treatment group were (17.9+/-7.3), (32.2+/-6.9), (18.5+/ 2.4) and (13.8+/-1.8) ml.(100 ml)(-1).min(-1,) respectively, and those in the control group were (10.5+/-0.6), (9.6+/-0.8), (5.7+/-1.2) and (1.9+/-1.0) ml.(100 ml)(-1).min(-1,) respectively. The values of VMI of the treatment group were 1.17+/-0.22, 3.25+/-0.23, 2.94+/-0.31 and 1.07+/-0.18, respectively, and those in the control group were 0.12+/-0.03, 0.13+/-0.03, 0.15+/-0.03, and 0.13+/-0.03, respectively. The values of MVD of the treatment group were (38.0+/-6.3), (24.3+/ 5.4), (15.2+/-3.4) and (13.5+/-4.7)/HPF, respectively, and those in the control group were (44.8+/-5.9), (48.0+/-12.8), (41.8+/-5.7) and (45.7+/-20.3)/HPF, respectively. In treated mice, BF and VMI were significantly higher than those in the control group (all P<0.01). BF and VMI increased from day2, and reached the peak at day4 (P<0.01), then decreased at day6, however the value of BF at day6 was still higher than that in the baseline (P<0.01) and decreased to the baseline level at day10; while the value of VMI was still higher than that in the baseline at day10. And on the forth, sixth, tenth days of treatment, in treated mice, the values of MVD were significantly lower than those in the control group and the baseline level before treatment (all P<0.01). In control mice, BF decreased (all P<0.01) with the time, while MVD and VMI had no changes. CONCLUSIONS: The tumor perfusion and vessel maturity are transiently increased in A549 lung adenocarcinoma transplantation model induced by antiangiogenic treatment. VPCT is helpful to quantify the evolution of the tumor perfusion and then evaluate the functional changes of tumor vessel maturity. PMID- 26879796 TI - Organo-Iodine(III)-Catalyzed Oxidative Phenol-Arene and Phenol-Phenol Cross Coupling Reaction. AB - The direct oxidative coupling reaction has been an attractive tool for environmentally benign chemistry. Reported herein is that the hypervalent iodine catalyzed oxidative metal-free cross-coupling reaction of phenols can be achieved using Oxone as a terminal oxidant in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This method features a high efficiency and regioselectivity, as well as functional-group tolerance under very mild reaction conditions without using metal catalysts. PMID- 26879797 TI - Stable Alkynyl Glycosyl Carbonates: Catalytic Anomeric Activation and Synthesis of a Tridecasaccharide Reminiscent of Mycobacterium tuberculosis Cell Wall Lipoarabinomannan. AB - Oligosaccharide synthesis is still a challenging task despite the advent of modern glycosidation techniques. Herein, alkynyl glycosyl carbonates are shown to be stable glycosyl donors that can be activated catalytically by gold and silver salts at 25 degrees C in just 15 min to produce glycosides in excellent yields. Benzoyl glycosyl carbonate donors are solid compounds with a long shelf life. This operationally simple protocol was found to be highly efficient for the synthesis of nucleosides, amino acids, and phenolic and azido glycoconjugates. Repeated use of the carbonate glycosidation method enabled the highly convergent synthesis of tridecaarabinomannan in a rapid manner. PMID- 26879799 TI - Endoscopic vocal fold injection using a 25-gauge butterfly needle. AB - OBJECTIVE: To describe a useful technique for infiltrating a bulking agent using a butterfly needle, as part of a transoral endoscopic vocal fold medialisation procedure. METHODS: This paper describes the procedure of grasping the needle with phonosurgery forceps and administering the injectate to the vocal fold through careful application of the syringe plunger via a length of rubber tubing from outside the mouth. RESULTS: This procedure is performed routinely in our institution without complication. The advantages of this technique are discussed. CONCLUSION: This is a safe and easy method of injecting into a vocal fold. PMID- 26879798 TI - Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology. AB - OBJECTIVES: Current repair procedures for articular cartilage (AC) cannot restore the tissue's original form and function because neither changes in its architectural blueprint throughout life nor the respective biological understanding is fully available. We asked whether two unique elements of human cartilage architecture, the chondrocyte-surrounding pericellular matrix (PCM) and the superficial chondrocyte spatial organization (SCSO) beneath the articular surface (AS) are congenital, stable or dynamic throughout life. We hypothesized that inducing chondrocyte proliferation in vitro impairs organization and PCM and induces an advanced osteoarthritis (OA)-like structural phenotype of human cartilage. METHODS: We recorded propidium-iodine-stained fetal and adult cartilage explants, arranged stages of organization into a sequence, and created a lifetime-summarizing SCSO model. To replicate the OA-associated dynamics revealed by our model, and to test our hypothesis, we transduced specifically early OA-explants with hFGF-2 for inducing proliferation. The PCM was examined using immuno- and auto-fluorescence, multiphoton second-harmonic-generation (SHG), and scanning electron microscopy (SEM). RESULTS: Spatial organization evolved from fetal homogeneity, peaked with adult string-like arrangements, but was completely lost in OA. Loss of organization included PCM perforation (local micro-fibrillar collagen intensity decrease) and destruction [regional collagen type VI (CollVI) signal weakness or absence]. Importantly, both loss of organization and PCM destruction were successfully recapitulated in FGF-2 transduced explants. CONCLUSION: Induced proliferation of spatially characterized early OA-chondrocytes within standardized explants recapitulated the full range of loss of SCSO and PCM destruction, introducing a novel in vitro methodology. This methodology induces a structural phenotype of human cartilage that is similar to advanced OA and potentially of significance and utility. PMID- 26879800 TI - A perfectly stoichiometric and flat CeO2(111) surface on a bulk-like ceria film. AB - In surface science and model catalysis, cerium oxide (ceria) is mostly grown as an ultra-thin film on a metal substrate in the ultra-high vacuum to understand fundamental mechanisms involved in diverse surface chemistry processes. However, such ultra-thin films do not have the contribution of a bulk ceria underneath, which is currently discussed to have a high impact on in particular surface redox processes. Here, we present a fully oxidized ceria thick film (180 nm) with a perfectly stoichiometric CeO2(111) surface exhibiting exceptionally large, atomically flat terraces. The film is well-suited for ceria model studies as well as a perfect substitute for CeO2 bulk material. PMID- 26879801 TI - Urinary tract infection pattern in adult women followed from childhood. AB - BACKGROUND: The aim of this study was to describe the pattern of urinary tract infection (UTI) and bladder function in women who had experienced recurrent UTI in childhood, with and without consequent renal damage, and followed for three to four decades. METHODS: A population-based cohort of women who had been followed from the first UTI in childhood and previously studied at a median age of 27 years was studied at a median age of 41 years. Renal damage was evaluated by (99m)Tc-dimercaptosuccinic acid scan. Clinical data were collected on the pattern of recurrent UTIs and bladder function. RESULTS: A total of 86 women were investigated, of whom 58 had suffered renal damage and 28 were without. Febrile UTI in adulthood had occurred in 22 patients, once in 15 women and twice or more in seven women. There was a change in the infection pattern over time, evident already in childhood, that was characterized by a decrease in UTI frequency and a shift from febrile to non-febrile infections. A significant association was found between renal damage and febrile UTI (p = 0.046), and between abnormal bladder function and recurrent non-febrile UTI (p = 0.002). There was no relationship between persisting vesicoureteral reflux (VUR) and proneness to either symptomatic UTI (p = 0.99) or febrile UTI in adulthood (p = 0.14). CONCLUSIONS: Among this study cohort there was a continuously decreasing rate of febrile UTI in adulthood. Persisting VUR was not related to UTI in adulthood. Abnormal bladder function was related to non-febrile UTI but not to febrile UTI. PMID- 26879802 TI - Continuous flow peritoneal dialysis (CFPD) improves ultrafiltration in children with acute kidney injury on conventional PD using a 4.25 % dextrose solution. AB - BACKGROUND: Criticism against the use of acute peritoneal dialysis (PD) has been its low clearance and low ultrafiltration (UF) volumes compared to extracorporeal techniques. The aim of our study was to determine whether continuous flow peritoneal dialysis (CFPD) would improve UF in children with acute kidney injury (AKI) in cases where UF on conventional PD was inadequate using 4.25 % glucose concentrations. METHODS: Five infants were prospectively studied. All had AKI with fluid overload. The median age of the patients was 6 (range 0.43-9) months; the median weight was 6.5 (range 2.7-8.4) kg. Each patient served as his or her own control, undergoing both CFPD and conventional PD. CFPD was performed with two bedside-placed catheters using a 2.5 % glucose concentration. After initial filling, a dialysate flow rate of 100 ml/min/1.73 m(2) was maintained with an adapted continuous venovenous haemofiltration machine. The UF flow rate was set at 2.5 ml/min/1.73 m(2) and adapted as necessary. UF and clearance rates were measured for both PD and CFPD. RESULTS: The median UF rate achieved was 1.7 (range 0.01-5.30) mg/kg/h with conventional PD versus 6.7 (range 2.17-15.7) mg/kg/h with CFPD (p = 0.042). The clearances of urea and creatinine were 6.89 (range 4.50-7.55) and 7.46 (range 4.79-10.50) mL/min/1.73 m(2), respectively, with conventional PD and 19 (17.0-30.0) and 41 (standard deviation17.4, range 12.0-52.0) mL/min/1.73 m(2), respectively, with CFPD (both p = 0.043). CONCLUSION: Continuous flow peritoneal dialysis improves UF in fluid overloaded infants who are not achieving adequate UF on conventional PD. PMID- 26879803 TI - Exogenous lipoid pneumonia in laryngectomy patients: Is ground glass opacity/crazy paving pattern an organizing pneumonia reaction that can predict poor outcome? PMID- 26879804 TI - Improving risk literacy in surgeons. AB - OBJECTIVE: To effectively practice evidence-based medicine, surgeons need to understand and be able to communicate health-relevant numerical information. We present the first study examining risk literacy in surgeons by assessing numeracy and surgical risk comprehension. Our study also investigated whether visual aids improve risk comprehension in surgeons with limited numeracy. METHODS: Participants were 292 surgeons from 60 countries who completed an instrument measuring numeracy and evaluated the results of a randomized controlled trial including post-surgical side-effects. Half of the surgeons received this information in numbers. The other half received the information represented visually. Accuracy of risk estimation, reading latency, and estimate latency (i.e., deliberation) were assessed. RESULTS: Some surgeons have low numeracy and could not correctly interpret surgical risks without additional support. Visual aids made risks transparent and eliminated differences in risk understanding between more and less numerate surgeons, increasing the amount of time that less numerate surgeons spent deliberating about risks. CONCLUSIONS: Visual aids can be an efficient and inexpensive means of improving risk comprehension and clinical judgement in surgeons with low numerical and statistical skills. PRACTICE IMPLICATIONS: Programs designed to help professionals represent and communicate health-relevant numerical information in simple transparent graphs may unobtrusively promote informed decision making. PMID- 26879805 TI - A systematic review of Motivational Interviewing interventions in cancer patients and survivors. AB - OBJECTIVE: To explore the use of Motivational Interviewing (MI) interventions among cancer patients and survivors, and determine aspects of intervention design that are common across successful MI interventions for this population. METHODS: We conducted a systematic review of studies addressing behavior change in cancer patients or survivors using Motivational Interviewing techniques. Studies were categorized into three groups based on behavioral outcome; lifestyle behaviors, psychosocial outcomes, and cancer-related symptom management. RESULTS: We included 15 studies in our analysis. Studies addressed behaviors such as diet, exercise, smoking cessation, cancer-related stress, and fatigue management. Counseling sessions varied in frequency and method of delivery, although telephone-based interventions were common. Trained oncology nurses often delivered MI sessions, and the majority of interventions included quality assessment to verify fidelity of MI techniques. CONCLUSION: Solid evidence exists for the efficacy of MI to address lifestyle behaviors as well as the psychosocial needs of cancer patients and survivors. More research is needed on the use of MI for self-management of cancer-related symptoms. PRACTICE IMPLICATIONS: Motivational Interviewing is a promising technique for addressing many types of behavior change in cancer patients or survivors. Intervention design must be sensitive to cancer type, phase of care, and complexity of desired behavior. PMID- 26879806 TI - Lead Levels in Landfill Areas and Childhood Exposure: An Integrative Review. AB - OBJECTIVE: Landfills are high-risk areas for environmental lead exposure for children living in poverty stricken areas in many countries. This review examines landfills and lead toxicity in children. The review discusses the effects of lead toxicity, provides evidenced based recommendations to reduce lead exposure, and identify gaps in the evidence. DESIGN AND SAMPLE: A database search was conducted of articles in English from 1985 to 2014. Ten articles met the inclusion criteria. The Whittemore and Knafl framework and the John Hopkins Research Evidence Appraisal Tool(c) were used for reviewing the data. RESULTS: Elevated blood lead levels (BLLs) of children living near landfills were related to increased soil lead levels. Toxic effects of lead included adverse outcomes such as encephalopathy or death for children. Different approaches to decrease lead level include environmental surveillance, BLL screening, and soil abatement which are costly. CONCLUSION: Increased BLL through environmental exposure is connected with poor health outcomes and death among children. Evidence-based prevention included monitoring and screening and costly soil abatement. It is recommended that future studies focus on community education for exposure avoidance for children living near landfill areas. PMID- 26879808 TI - Sustaining integrating imatinib and interferon-alpha into maintenance therapy improves survival of patients with Philadelphia positive acute lymphoblastic leukemia ineligible for allogeneic stem cell transplantation. AB - We report the clinical results of sustainedly integrating imatinib and interferon alpha into maintenance therapy in the patients ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Maintenance therapy lasted for 5 years with imatinib 400 mg daily, interferon-alpha 3 million units, 2~3 doses per week, and chemotherapy including vindesine and dexamethasone scheduled monthly in first year, once every 2 months in second year, and once every 3 months in third year. The chemotherapy was discontinued after 3 years and the imatinib and interferon-alpha continued for another 2 years. For 41 patients without allo-HSCT with a median follow-up of 32 months, the 3-year DFS and OS were 42.7 +/- 8.6% and 57.9 +/- 8.4%, respectively. Our study suggests that sustaining maintenance with low-dose chemotherapy, imatinib and interferon-alpha improved survival of adult Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) patients ineligible for allo-HSCT, and even provided an opportunity for cure. BCR/ABL persistent negativity at 6 and 9 months may have benefit to choose suitable patients for the imatinib/interferon-alpha maintenance strategy. PMID- 26879807 TI - Long-term intravenous inotropes in low-output terminal heart failure? AB - Intravenous inotropic therapy may be necessary to achieve short-term survival in end-stage heart failure patients with cardiogenic shock or extreme low output and severe organ hypoperfusion. However, mid- or long-term intravenous inotropic therapy is associated with an increased mortality in advanced stage D heart failure patients using beta-adrenoceptor agonists (dobutamine) or PDE-3 inhibitors (milrinone). Intermittent levosimendan may evolve as a reasonable therapeutic option. Randomized trials or other meaningful scientific evidence addressing the optimal treatment of exclusively the most threatened subgroup of hospitalized patients with persistent severe organ hypoperfusion are missing, but urgently needed. Despite a lack of other beneficial pharmacological options, the use of long-term intravenous inotropic therapy as a treatment for refractory heart failure or as an obligatory criterion for high urgency (HU) listing of heart transplant candidates with a median waiting time of 66 days in Germany is not based on scientific evidence. In addition, it might create a disincentive to achieve the HU status as well as keeping it, thereby potentially exposing the patient to an unnecessary additional risk. Upcoming new allocation algorithms may possibly help to improve the inadequate present situation. There is need for both, a better definition and a better treatment of high risk terminal heart failure requiring high urgent transplant listing. PMID- 26879810 TI - Association between television viewing time and risk of incident stroke in a general population: Results from the REGARDS study. AB - OBJECTIVES: The purpose of this study was to explore the relationship between TV/video viewing, as a measure of sedentary behavior, and risk of incident stroke in a large prospective cohort of men and women. METHODS: This analysis involved 22,257 participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported at baseline the amount of time spent watching TV/video daily. Suspected stroke events were identified at six-monthly telephone calls and were physician-adjudicated. Cox proportional hazards models were used to examine risk of stroke at follow-up. RESULTS: During 7.1years of follow-up, 727 incident strokes occurred. After adjusting for demographic factors, watching TV/video >=4h/day (30% of the sample) was associated with a hazard ratio of 1.37 increased risk of all stroke (95% confidence interval (CI), 1.10-1.71) and incident ischemic stroke (hazard ratio 1.35, CI 1.06-1.72). This association was attenuated by socioeconomic factors such as employment status, education and income. CONCLUSIONS: These results suggest that while TV/video viewing is associated with increased stroke risk, the effect of TV/video viewing on stroke risk may be explained through other risk factors. PMID- 26879811 TI - Is the Risk of Diabetic Ketoacidosis Modifiable? PMID- 26879809 TI - Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. AB - Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects. PMID- 26879812 TI - Anxiety Adversely Impacts Response to Cognitive Behavioral Therapy in Children with Chronic Pain. AB - OBJECTIVE: To evaluate whether clinical anxiety in children presenting to a pediatric pain management center is associated with a poorer treatment response for those who completed pain-focused cognitive behavioral therapy (CBT). STUDY DESIGN: The total sample consisted of 175 children, 40 of whom completed CBT for chronic pain. The Screen for Child Anxiety Related Emotional Disorders was completed at initial evaluation and outcome measures (average pain intensity and the Functional Disability Inventory) were collected during the initial evaluation and at the end of CBT. Group differences in outcomes were examined following CBT. The role of anxiety in CBT initiation and completion was also explored. RESULTS: Presence of clinical anxiety was associated with greater initiation and/or completion of pain-focused CBT but also a poorer treatment response. Specifically, the group with subclinical anxiety exhibited a substantial reduction in pain intensity, and the group with clinical anxiety exhibited a more limited response to treatment (F [1, 36] = 13.68 P < .01). A similar effect was observed for Functional Disability Inventory, such that the group with clinical anxiety had a significantly smaller response to treatment (F [1, 38] = 4.33 P < .05). The difference in pain and disability between groups following CBT suggest moderate effects (Cohen d = 0.77 and 0.78, respectively). CONCLUSIONS: Although youths with clinical anxiety are more likely to start and/or complete pain focused CBT, anxiety has an adverse impact on CBT treatment response in children with chronic pain. Identification of patients with anxiety and use of tailored behavioral interventions may improve clinical outcomes. PMID- 26879813 TI - Recent Developments in p-Type Oxide Semiconductor Materials and Devices. AB - The development of transparent p-type oxide semiconductors with good performance may be a true enabler for a variety of applications where transparency, power efficiency, and greater circuit complexity are needed. Such applications include transparent electronics, displays, sensors, photovoltaics, memristors, and electrochromics. Hence, here, recent developments in materials and devices based on p-type oxide semiconductors are reviewed, including ternary Cu-bearing oxides, binary copper oxides, tin monoxide, spinel oxides, and nickel oxides. The crystal and electronic structures of these materials are discussed, along with approaches to enhance valence-band dispersion to reduce effective mass and increase mobility. Strategies to reduce interfacial defects, off-state current, and material instability are suggested. Furthermore, it is shown that promising progress has been made in the performance of various types of devices based on p type oxides. Several innovative approaches exist to fabricate transparent complementary metal oxide semiconductor (CMOS) devices, including novel device fabrication schemes and utilization of surface chemistry effects, resulting in good inverter gains. However, despite recent developments, p-type oxides still lag in performance behind their n-type counterparts, which have entered volume production in the display market. Recent successes along with the hurdles that stand in the way of commercial success of p-type oxide semiconductors are presented. PMID- 26879814 TI - Modulation of monocytes in septic patients: preserved phagocytic activity, increased ROS and NO generation, and decreased production of inflammatory cytokines. AB - BACKGROUND: The nature of the inflammatory response underscoring the pathophysiology of sepsis has been extensively studied. We hypothesized that different cell functions would be differentially regulated in a patient with sepsis. We evaluated the modulation of monocyte functions during sepsis by simultaneously assessing their phagocytic activity, the generation of reactive oxygen species (ROS) and nitric oxide (NO), and the production of inflammatory cytokines (IL-6 and TNF-alpha). METHODS: Whole blood was obtained from patients with severe sepsis and septic shock both at admission (D0, n = 34) and after seven days of therapy (D7, n = 15); 19 healthy volunteers were included as a control group. The cells were stimulated with LPS, Pseudomonas aeruginosa, and Staphylococcus aureus. The ROS and NO levels were quantified in monocytes in whole blood by measuring the oxidation of 2,7-dichlorofluorescein diacetate and 4 amino-5-methylamino-2,7-difluorofluorescein diacetate, respectively. Intracellular IL-6 and TNF-alpha were detected using fluorochrome-conjugated specific antibodies. Monocyte functions were also evaluated in CD163+ and CD163- monocyte subsets. RESULTS: The monocytes from septic patients presented with preserved phagocytosis, enhanced ROS and NO generation, and decreased production of inflammatory cytokines compared with the monocytes from healthy volunteers. TNF-alpha and IL-6 increased and ROS generation decreased in D7 compared with D0 samples. In general, CD163+ monocytes produced higher amounts of IL-6 and TNF alpha and lower amounts of ROS and NO than did CD163- monocytes. CONCLUSIONS: We demonstrated that monocytes from septic patients, which are impaired to produce inflammatory cytokines, display potent phagocytic activity and increased ROS and NO generation. PMID- 26879815 TI - Distribution of allelic and genotypic frequencies of IL1A, IL4, NFKB1 and PAR1 variants in Native American, African, European and Brazilian populations. AB - BACKGROUND: The inflammatory response plays a key role at different stages of cancer development. Allelic variants of the interleukin 1A (IL1A), interleukin 4 (IL4), nuclear factor kappa B1 (NFKB1) and protease-activated receptor 1 (PAR1) genes may influence not only the inflammatory response but also susceptibility to cancer development. Among major ethnic or continental groups, these polymorphic variants present different allelic frequencies. In admixed populations, such as the Brazilian population, data on distribution of these polymorphisms are limited. Here, we collected samples of cancer-free individuals from the north, northeast, midwest, south and southeast regions of Brazil and from the three main groups that gave rise to the Brazilian population: Native Americans from the Brazilian Amazon, Africans and Europeans. We describe the allelic distributions of four IL1A (rs3783553), IL4 (rs79071878), NFKB1 (rs28362491) and PAR1 (rs11267092) gene polymorphisms, which the literature describes as polymorphisms with a risk of cancer or worse prognosis for cancer. RESULTS: The genotypic distribution of the four polymorphisms was statistically distinct between Native Americans, Africans and Europeans. For the allelic frequency of these polymorphisms, the Native American population was the most distinct among the three parental populations, and it included the greatest number of alleles with a risk of cancer or worse prognosis for cancer. The PAR1 gene polymorphism allelic distribution was similar among all Brazilian regions. For the other three markers, the northern region population was statistically distinct from other Brazilian region populations. CONCLUSION: The IL1A, IL4, NFKB1 and PAR1 gene polymorphism allelic distributions are homogeneous among the regional Brazilian populations, except for the northern region, which significantly differs from the other four Brazilian regions. Among the parental populations, the Native American population exhibited a higher incidence of alleles with risk of cancer or worse prognosis for cancer, which can indicate greater susceptibility to this disease. These genetic data may be useful for future studies on the association between these polymorphisms and cancer in the investigated populations. PMID- 26879816 TI - Population pharmacokinetic properties of artemisinin in healthy male Vietnamese volunteers. AB - BACKGROUND: Artemisinin-based combination therapy is recommended as first-line anti-malarial treatment worldwide. A combination of artemisinin with the long acting drug piperaquine has shown high efficacy and tolerability in patients with uncomplicated Plasmodium falciparum infections. The aim of this study was to characterize the population pharmacokinetic properties of artemisinin in healthy male Vietnamese volunteers after two different dose sizes, formulations and in a combination with piperaquine. A secondary aim was to compare two different methods for the evaluation of bioequivalence of the formulations. METHODS: Fifteen subjects received four different dose regimens of a single dose of artemisinin as a conventional formulation (160 and 500 mg) and as a micronized test formulation (160 mg alone and in combination with piperaquine phosphate, 360 mg) with a washout period of 3 weeks between each period (i.e. four-way cross over). Venous plasma samples were collected frequently up to 12 h after dose in each period. Artemisinin was quantified in plasma using liquid chromatography coupled with tandem mass spectrometry. A nonlinear mixed-effects modelling approach was utilized to evaluate the population pharmacokinetic properties of the drug and to investigate the clinical impact of different formulations. RESULTS: The plasma concentration-time profiles for artemisinin were adequately described by a transit-absorption model with a one-compartment disposition, in all four sequences simultaneously. The mean oral clearance, volume of distribution and terminal elimination half-life was 417 L/h, 1210 L and 1.93 h, respectively. Influence of formulation, dose and possible interaction of piperaquine was evaluated as categorical covariates in full covariate approaches. No clinically significant differences between formulations were shown which was in accordance with the previous results using a non-compartmental bioequivalence approach. CONCLUSIONS: This is the first population pharmacokinetic characterization of artemisinin in healthy volunteers. Increasing the dose resulted in a significant increase in the mean transit-time but the micronized formulation or concomitant piperaquine administration did not affect the pharmacokinetic properties of artemisinin. The results from the traditional bioequivalence evaluation were comparable with results obtained from mixed effects modelling. PMID- 26879817 TI - Childhood and adolescent influenza vaccination in Europe: A review of current policies and recommendations for the future. AB - Children and adolescents experience some of the highest rates of influenza infection and the subsequent burden on both infected children and their parents/carers is substantial. Vaccinating children and adolescents against seasonal influenza has the potential to reduce the burden of disease in both vaccinated and unvaccinated individuals due to the pivotal role that younger age groups play in the transmission of infection. While countries such as the USA, Canada and the UK have consequently recommended the universal vaccination of children, the vast majority of European countries have not yet extended their vaccination policies to this age group. This review examines the rationale for childhood and adolescent vaccination against seasonal influenza and reviews current vaccination policies in Europe. We discuss key policy considerations for European countries that must be considered when extending vaccination programmes to younger age groups alongside recommendations for European policy makers based on our findings. PMID- 26879818 TI - Nitroxyl as a ligand in ruthenium tetraammine systems: a density functional theory study. AB - The properties of the free nitroxyl molecule and the nitroxyl ligand in Ru(ii) tetraammines (trans-[Ru(NH3)4(nitroxyl)(n)(L)](2+n) (n = nitroxyl charge; L = NH3, py, P(OEt)3, H2O, Cl(-) and Br(-))) were studied using density functional theory. According to the calculated conformational energies, HNO complexes are more stable than their deprotonated analogues, and the singlet configuration (trans-(1)[Ru(NH3)4(L)HNO](2+)) is lower in energy than the corresponding triplet (trans-(3)[Ru(NH3)4(L)HNO](2+)). An evaluation of the sigma and pi components of the L-Ru-HNO bond suggest that the increased stability of these orbitals and the enhanced contributions from the HNO orbitals correlate to shorter Ru-N(H)O distances and higher nuRu-HNO stretching frequencies. The stability of the Ru-HNO bond was also evaluated through a theoretical kinetic study of HNO dissociation from trans-(1)[Ru(NH3)4(L)HNO](2+). The order of the Ru-HNO bonding stability in trans-(1)[Ru(NH3)4(L)HNO](2+) as a function of L was found to be as follows: H2O > Cl(-)~ Br(-) > NH3 > py > P(OEt)3. This order parallels the order of the trans effect and trans-influence series experimentally measured for L in octahedral complexes. The same trend was also observed using an explicit solvent model, considering the presence of both HNO and H2O molecules in the transition state. For this series, the calculated bond dissociation enthalpies for the Ru-HNO bonds are in the range 23.8 to 45.7 kcal mol(-1). A good agreement was observed between the calculated DeltaG(?) values for the displacement of HNO by H2O in trans (1)[Ru(NH3)4(P(OEt)3HNO](2+) (23.4 kcal mol(-1)) and the available experimental data for the substitution reactions of trans[Ru(NH3)4(POEt)3(Lx)](2+) (19.4 to 24.0 kcal mol(-1) for Lx = isn and P(OET)3, respectively). PMID- 26879819 TI - Osteoporosis Associated with Epilepsy and the Use of Anti-Epileptics-a Review. AB - The increased rate of fractures associated with epilepsy has been long recognised but remains incompletely understood. Study quality and study results have varied, with some but not all studies showing bone diseases including osteoporosis and/or osteomalacia, and a high prevalence of vitamin D insufficiency and deficiency are also noted. Falls risk can also be higher in patients with epilepsy taking anti epileptic medications, potentially leading to fracture. Larger research collaborations are recommended to further advance understanding in this field, particularly to examine underlying genetic and pharmacogenomic associations of epilepsy and anti-epileptic medication usage and its association with bone diseases and fractures, as well as further investigation into optimal management of bone health in epilepsy. PMID- 26879821 TI - [Rare case of a mesenteric tumor]. PMID- 26879820 TI - [Contralateral hepatic hypertrophy following unilateral yttrium-90 radioembolization : Implications for liver surgery]. AB - BACKGROUND: Preservation of an adequate future liver remnant (FLR) is the principal limitation to liver surgery in patients with primary or secondary liver malignancies. Hence, methods to increase the volume of the FLR in preparation for liver resection are gaining in importance. OBJECTIVE: In addition to the traditional methods for induction of FLR hypertrophy, such as portal vein embolization (PVE) or portal vein ligation (PVL) with or without parenchymal dissection (ALPPS, in situ split), radioembolization (RE) using yttrium-90 microspheres also leads to a volume increase of non-embolized liver parenchyma. This review outlines its potential role as an alternative procedure for induction of liver hypertrophy. MATERIAL AND METHODS: Synopsis and critical discussion of the available literature on the mechanisms of induction of liver hypertrophy, the advantages and drawbacks of the traditional methods, and current research on volume changes associated with RE as well as their implications for possible clinical use in preparation for liver surgery. RESULTS: Both PVE and PVL can achieve a substantial contralateral volume gain of up to 70 %. The development of contralateral hypertrophy can be accelerated by dissecting the liver parenchyma along the intended plane of resection in addition to PVL (in situ split). Compared to these methods, RE achieves less contralateral liver hypertrophy; however, this effect should not be disregarded as RE provides effective treatment of ipsilateral liver tumors along with induction of hypertrophy and may be associated with a reduced risk of tumor progression compared to PVE and PVL. CONCLUSION: The available data suggest that RE can complement the armamentarium of methods for induction of FLR hypertrophy in specific situations. Further studies are needed to establish its definitive role for this indication and are in preparation. PMID- 26879822 TI - Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project. AB - INTRODUCTION AND AIMS: We aimed to characterise motor performance in predominantly Aboriginal children living in very remote Australia, where rates of prenatal alcohol exposure (PAE) are high. Motor performance was assessed, and the relationship between motor skills, fetal alcohol spectrum disorders (FASD) and PAE was explored. DESIGN AND METHODS: Motor performance was assessed using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition Complete Form, in a population-based study of children born in 2002 or 2003 living in the Fitzroy Valley, Western Australia. Composite scores >=2SD (2nd percentile) and >=1SD (16th percentile) below the mean were used respectively for FASD diagnosis and referral for treatment. FASD diagnoses were assigned using modified Canadian Guidelines. RESULTS: A total of 108 children (Aboriginal: 98.1%; male: 53%) with a mean age of 8.7 years was assessed. The cohort's mean total motor composite score (mean +/- SD 47.2 +/- 7.6) approached the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition normative mean (50 +/- 10). Motor performance was lower in children with FASD diagnosis than without (mean difference (MD) +/- SD: 5.0 +/- 1.8; confidence interval: -8.6 to -1.5). There was no difference between children with PAE than without (MD +/- SE: -2.2 +/- 1.5; confidence interval: 5.1 to 0.80). The prevalence of motor impairment (>=-2SD) was 1.9% in the entire cohort, 9.5% in children with FASD, 3.3% in children with PAE and 0.0% both in children without PAE or FASD. DISCUSSION AND CONCLUSIONS: Almost of 10% of children with FASD has significant motor impairment. Evaluation of motor function should routinely be included in assessments for FASD, to document impairment and enable targeted early intervention.[Lucas BR, Doney R, Latimer J, Watkins RE, Tsang TW, Hawkes G, Fitzpatrick JP, Oscar J, Carter M, Elliott EJ. Impairment of motor skills in children with fetal alcohol spectrum disorders in remote Australia: The Lililwan Project. Drug Alcohol Rev 2016;35:719-727]. PMID- 26879823 TI - Development of non-defective recombinant densovirus vectors for microRNA delivery in the invasive vector mosquito, Aedes albopictus. AB - We previously reported that mosquito densoviruses (MDVs) are potential vectors for delivering foreign nucleic acids into mosquito cells. However, considering existing expression strategies, recombinant viruses would inevitably become replication-defective viruses and lose their ability for secondary transmission. The packaging limitations of the virion represent a barrier for the development of MDVs for viral paratransgenesis or as high-efficiency bioinsecticides. Herein, we report the development of a non-defective recombinant Aedes aegypti densovirus (AaeDV) miRNA expression system, mediated by an artificial intron, using an intronic miRNA expression strategy. We demonstrated that this recombinant vector could be used to overexpress endogenous miRNAs or to decrease endogenous miRNAs by generating antisense sponges to explore the biological functions of miRNAs. In addition, the vector could express antisense-miRNAs to induce efficient gene silencing in vivo and in vitro. The recombinant virus effectively self-replicated and retained its secondary transmission ability, similar to the wild-type virus. The recombinant virus was also genetically stable. This study demonstrated the first construction of a non-defective recombinant MDV miRNA expression system, which represents a tool for the functional analysis of mosquito genes and lays the foundation for the application of viral paratransgenesis for dengue virus control. PMID- 26879824 TI - The heterogeneous energy landscape expression of KWW relaxation. AB - Here we show a heterogeneous energy landscape approach to describing the Kohlrausch-Williams-Watts (KWW) relaxation function. For a homogeneous dynamic process, the distribution of free energy landscape is first proposed, revealing the significance of rugged fluctuations. In view of the heterogeneous relaxation given in two dynamic phases and the transmission coefficient in a rate process, we obtain a general characteristic relaxation time distribution equation for the KWW function in a closed, analytic form. Analyses of numerical computation show excellent accuracy, both in time and frequency domains, in the convergent performance of the heterogeneous energy landscape expression and shunning the catastrophic truncations reported in the previous work. The stretched exponential beta, closely associated to temperature and apparent correlation with one dynamic phase, reveals a threshold value of 1/2 defining different behavior of the probability density functions. Our work may contribute, for example, to in-depth comprehension of the dynamic mechanism of glass transition, which cannot be provided by existing approaches. PMID- 26879825 TI - Attitudes and preferences toward monitoring symptoms, distress, and quality of life in glioma patients and their informal caregivers. AB - PURPOSE: Glioma patients and their informal caregivers face many challenges in living with the disease and its disease-specific consequences. To better meet their needs, a system to monitor symptoms, distress, and quality of life could prove useful. We explored glioma patients' and caregivers' attitudes and preferences toward monitoring in general and specifically toward paper-and-pencil and computerized (eHealth) options. METHODS: In total, 15 patients and 15 informal caregivers participated in individual, semi-structured interviews. Interviews were transcribed smooth verbatim and coded by two researchers independently. RESULTS: Advantages of monitoring generated by participants include increased awareness of problems and their flow over time, and facilitating supportive care provision. Disadvantages include investment of time and mastering the discipline to monitor frequently. Patients reported more disadvantages of monitoring, including practical and disease-specific impediments, while caregivers mentioned more advantages. Preferences for specific methods mentioned to monitor are highly personal but most prefer to have an option for face-to-face contact to discuss results of monitoring with health care professionals even in computerized instruments. CONCLUSIONS: Informal caregivers view a monitoring system more favorably than glioma patients. In developing an efficient monitoring system to help glioma patients and caregivers find their way to supportive care, a computerized instrument with the added opportunity to contact a health care professional seems to be the best option to advise. PMID- 26879826 TI - Safe RESIDential Environments? A longitudinal analysis of the influence of crime related safety on walking. AB - BACKGROUND: Numerous cross-sectional studies have investigated the premise that the perception of crime will cause residents to constrain their walking; however the findings to date are inconclusive. In contrast, few longitudinal or prospective studies have examined the impact of crime-related safety on residents walking behaviours. This study used longitudinal data to test whether there is a causal relationship between crime-related safety and walking in the local neighbourhood. METHODS: Participants in the RESIDential Environments Project (RESIDE) in Perth, Australia, completed a questionnaire before moving to their new neighbourhood (n = 1813) and again approximately one (n = 1467), three (n = 1230) and seven years (n = 531) after relocating. Self-report measures included neighbourhood perceptions (modified NEWS items) and walking inside the neighbourhood (min/week). Objective built environmental measures were generated for each participant's 1600 m neighbourhood at each time-point, and the count of crimes reported to police were generated at the suburb-level for the first three time-points only. The impact of crime-related safety on walking was examined in SAS using the Proc Mixed procedure (marginal repeated measures model with unrestricted variance pattern). Initial models controlled for demographics, time and self-selection, and subsequent models progressively adjusted for other built and social environment factors based on a social ecological model. RESULTS: For every increase of one level on a five-point Likert scale in perceived safety from crime, total walking within the local neighbourhood increased by 18.0 min/week (p = 0.000). This relationship attenuated to an increase of 10.5 min/week after accounting for other built and social environment factors, but remained significant (p = 0.008). Further analyses examined transport and recreational walking separately. In the fully adjusted models, each increase in safety from crime was associated with a 7.0 min/week increase in recreational walking (p = 0.009), however findings for transport walking were non-significant. All associations between suburb-level crime and walking were non-significant. CONCLUSIONS: This study provides longitudinal evidence of a potential causal relationship between residents' perceptions of safety from crime and recreational walking. Safety perceptions appeared to influence recreational walking, rather than transport-related walking. Given the popularity of recreational walking and the need to increase levels of physical activity, community social and physical environmental interventions that foster residents' feelings of safety are likely to increase recreational walking and produce public health gains. PMID- 26879827 TI - Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist. AB - OBJECTIVE: The objective of the present study was to compare the effects of pitolisant on QTcF interval in a single ascending dose (SAD) study and a thorough QT (TQT) study. METHODS: The SAD study at three dose levels of pitolisant enrolled 24 males and the TQT study at two dose levels 25 males. Both studies intensively monitored ECGs and pitolisant exposure. Effect on QTcF interval was analysed by Intersection Union Test (IUT) and by exposure-response (ER) analysis. Results from the two studies were compared. RESULTS: In both studies, moxifloxacin effect established assay sensitivity. IUT analysis revealed comparable pitolisant-induced maximum mean (90 % confidence interval (CI)) placebo-corrected increase from baseline (DeltaDeltaQTcF) in both the studies, being 13.3 (8.1; 18.5) ms at 200-mg and 9.9 (4.7; 15.1) ms at 240-mg doses in SAD study and 5.27 (2.35; 8.20) ms at 120-mg dose in TQT study. ER analysis revealed that ER slopes in SAD and TQT studies were comparable and significantly positive (0.031 vs 0.027 ms/ng/mL, respectively). At geometric mean concentrations, bootstrap predicted DeltaDeltaQTcF (90 % CI) were 9.23 (4.68; 14.4) ms at 279 ng/mL (240-mg dose) in the SAD study and 4.97 (3.42; 8.19) ms at 156 ng/mL (120 mg dose) in the TQT study. CONCLUSION: Pitolisant lacked an effect of regulatory concern on QTc interval in both the studies, however analysed, suggesting that the results from the SAD study could have mitigated the need for a TQT study. Our findings add to the growing evidence that intensive ECG monitoring in early phase clinical studies can replace a TQT study. PMID- 26879828 TI - A Contextualized Approach to Faith-Based HIV Risk Reduction for African American Women. AB - HIV/AIDS has a devastating impact on African Americans, particularly women and young adults. We sought to characterize risks, barriers, and content and delivery needs for a faith-based intervention to reduce HIV risk among African American women ages 18 to 25. In a convergent parallel mixed methods study, we conducted four focus groups (n = 38) and surveyed 71 young adult women. Data were collected across four African American churches for a total of 109 participants. We found the majority of women in this sample were engaged in behaviors that put them at risk for contracting HIV, struggled with religiously based barriers and matters of sexuality, and had a desire to incorporate their intimate relationships, parenting, and financial burdens into faith-based HIV risk-reduction interventions. Incorporating additional social context-related factors into HIV risk-reduction interventions for young African American women is critical to adapting and developing HIV interventions to reduce risk among young adult women in faith settings. PMID- 26879829 TI - Validation of an Interaction Model of Health Behavior Among Adults With Hypertension. AB - The purpose of this study was to test the Interaction Model of Client Health Behavior among adults with hypertension. The predictive associations among health literacy, quality of the provider interaction, perceived communication skills, and behavioral activation on blood pressure control were examined. Participants were 109 adults with hypertension recruited from community settings. A path analysis using maximum likelihood estimation was conducted in Analysis of Moment Structures for Windows (AMOS). The model fit to these data was excellent (chi(2) = 1.1, p = .76, Tucker-Lewis index [TLI] = 1.1, comparative fit index [CFI] = 1.0, root mean square error of approximation [RMSEA] = .00, standardized root mean residual [SRMR] = .03). As hypothesized, health literacy, quality of the provider interaction, and perceived communication skills directly affected behavioral action. The quality of the provider interaction, perceived communication skills, and behavioral activation had direct effects on systolic blood pressure control. The study results support health literacy screening and communication skill building, and improving the quality of provider interactions to enhance blood pressure control among adults with hypertension. PMID- 26879830 TI - Teaching research: a programme to develop research capacity in undergraduate medical students at the University of KwaZulu-Natal, South Africa. AB - BACKGROUND: Improved research ability is a core competency to achieve in health professionals. The Selectives is a three-year, longitudinal, community-based programme within the undergraduate curriculum which aims to develop research capacity in all medical students during the prescribed curriculum. In relation to the programme, the authors describe the types of studies conducted by students, conditions that facilitated their learning, how the experience improved students' knowledge of research and public health and their development of reflective learning practices. METHODS: A cohort of 212 students completed the Selectives Programme in 2014, and 69 (32 %) completed an anonymous online evaluation thereafter. Data collected include students' perceptions of the research component of Selectives; its impact on their knowledge of research and a documentary analysis of their research protocols and posters. Ethical approval for the ongoing evaluation of the Selectives was sought and obtained from the institutional Biomedical Research Ethics Committee. RESULTS: During Selectives, 75 groups of 2-4 students conducted research studies of primary health care problems in community settings. Each group is assessed on their presentation of research findings as a scientific poster. The Selectives facilitated learning for the majority of the cohort. Students reported positive learning experiences about the research process, including ethics; protocol writing; data processing; dissemination of findings and results; and their use in informing a health promotion intervention. Students reported having gained a better understanding of their strengths and weaknesses through reflective learning from this academic activity. The Selectives is scheduled adjacent to the students' mid-year vacation. This scheduling together with the placement in the students' home community minimizes travel and accommodation costs associated with working outside the academic teaching platform and therefore makes it a cost-effective model in a low resource context. CONCLUSIONS: The Selectives has proven beneficial to develop a range of generic and practical research competencies for a full cohort of students enrolled in the undergraduate medical curriculum. The Selectives research process is integrated with learning about population health and the social determinants of health in a primary health care setting. PMID- 26879831 TI - Invasive occipital nerve stimulation for refractory chronic cluster headache: what evolution at long-term? Strengths and weaknesses of the method. AB - BACKGROUND: Invasive Occipital Nerve Stimulation (iONS) is a costly technique which appears effective in drug-refractory chronic cluster headache (drCCH) management. Available data on long-term effectiveness and safety of iONS in this indication are scarce, though they could be useful to neurologists and patients in daily practice. The purpose of this short report is to discuss the very long term outcome of a drCCH cohort, including adverse events. FINDINGS: Previously, favourable results were obtained with iONS in 15 drCCH patients: 80 % were significantly improved and 60 % were pain free. We report here the very long-term follow-up (up to nine years) of 10 patients belonging to this cohort. Meanwhile 5 patients had to be definitively explanted because of device infection (3) or paresthesia intolerance (2). Four patients (40 %) evolved to an episodic form of CH. Six remained chronic but their attack frequency was decreased by 70 % on average. Intake of preventive drugs is still necessary in 80 % of patients. All patients needed at least one battery replacement. CONCLUSIONS: Up to nine years after implantation, iONS is still effective in most patients with drCCH. Concomitant preventive drugs remain often necessary. Forty percent of patients reverse to episodic CH, possibly by natural history. iONS is not a benign procedure but device-related complications appear similar to those reported with other invasive neurostimulators. PMID- 26879833 TI - Tacrolimus Trough Levels as a Risk Factor for Acute Rejection in Renal Transplant Patients. AB - BACKGROUND: Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS: This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Cox's proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed. RESULTS: We included 198 patients with an average age of 32 years (+/-12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow up duration. CONCLUSIONS: In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events. PMID- 26879832 TI - Interictal burden attributable to episodic headache: findings from the Eurolight project. AB - BACKGROUND: Most primary headaches are episodic, and most estimates of the heavy disability burden attributed to headache derive from epidemiological data focused on the episodic subtypes of migraine and tension-type headache (TTH). These disorders give rise directly but intermittently to symptom burden. Nevertheless, people with these disorders may not be symptom-free between attacks. We analysed the Eurolight dataset for interictal burden. METHODS: Eurolight was a cross sectional survey using modified cluster sampling from the adult population (18-65 years) in 10 countries of the European Union. We used data from nine. The questionnaire included headache-diagnostic questions based on ICHD-II and several question sets addressing impact, including interictal and cumulative burdens. RESULTS: There were 6455 participants with headache (male 2444 [37.9 %]). Interictal symptoms were reported by 26.0 % of those with migraine and 18.9 % with TTH: interictal anxiety by 10.6 % with migraine and avoidance (lifestyle compromise) by 14.8 %, both much more common than in TTH (3.1 % [OR 3.8] and 4.7 % [OR 3.5] respectively). Mean time spent in the interictal state was 317 days/year for migraine, 331 days/year for TTH. Those who were "rarely" or "never" in control of their headaches (migraine 15.2 %, TTH 9.6 %) had significantly raised odds of interictal anxiety, avoidance and other interictal symptoms. Among those with migraine, interictal anxiety increased markedly with headache intensity and frequency, avoidance less so but still significantly. Lost productive time was associated with high ORs (up to 5.3) of anxiety and avoidance. A third (32.9 %) with migraine and a quarter (26.7 %) with TTH (difference: p < 0.0001) were reluctant to tell others of their headaches. About 10 % with each disorder felt families and friends did not understand their headaches. Nearly 12 % with migraine reported their employers and colleagues did not. Regarding cumulative burden, 11.8 % reported they had done less well in education because of headache, 5.9 % reported reduced earnings and 7.4 % that their careers had suffered. CONCLUSIONS: Interictal burden in those with episodic headache is common, more so in migraine than TTH. Some elements have the potential to be profoundly consequential. New methodology is needed to measure interictal burden if descriptions of headache burden are to be complete. PMID- 26879834 TI - Increased urinary 6-hydroxymelatoninsulfate levels in attention deficit hyperactivity disorder diagnosed children and adolescent. AB - There are some studies in attention deficit hyperactivity disorder (ADHD) which note altered circadian rhythms, suggesting abnormalities in melatonin physiology. In order to better characterize the possible melatonin alteration in ADHD, in this study we aimed to detect daytime, nighttime and 24 h levels of 6 hydroxymelatoninsulfate (6-OH MS) in the patients diagnosed with ADHD. Twenty seven patients between 6 and 16 years-old, who had been diagnosed initially with ADHD, but without other physical and psychiatric disease history and who had not taken psychotropic pharmacotherapy for six months, plus 28 healthy volunteer controls, were included in the study. Urine samples were collected during the whole 24 h cycle, daytime and nighttime separately to assess the time-dependent excretion of the 6-OH MS, which is the main urine metabolite of melatonin. The Enzyme-Linked Immunosorbent Assay (ELISA) method was used for measuring the urine 6-OH MS level. Daytime (15.4 (8.9-24.8) ng/ml vs 6.9 (2.5-15.9) ng/ml, p=0.002), nighttime (102.9 (65.3-197.7) ng/ml vs 61.5 (37.2-114.4) ng/ml, p=0.012) and 24 h (54.1 (34.6-83.9) ng/ml vs 27.3 (14.3-48.9) ng/ml, p=0.000) 6-OH MS levels median (25p-75p) were found to be significantly higher in the ADHD group. After adjustment for age and sex, there was a statistically significant difference between the ADHD group (59.8 +/- 4.9) and control group (33.8 +/- 4.8) in 24-h 6 OH MS levels (F(1, 51)=13.673, p=.001, partial eta2=.211). There was no relationship between 6-OH MS levels and Conners Parent Rating Scale short form subscale scores for the ADHD group. These findings indicate that melatonin production is increased in ADHD cases. Further research is needed to determine and thereby understand the mechanisms underlying the higher melatonin production, to assess the impact of altered melatonin on the pathophysiology of ADHD. PMID- 26879835 TI - Z-guggulsterone negatively controls microglia-mediated neuroinflammation via blocking IkappaB-alpha-NF-kappaB signals. AB - Induction of pro-inflammatory factors is one of the characteristics of microglial activation and can be regulated by numerous active agents extracted from plants. Suppression of pro-inflammatory factors is beneficial to alleviate neuroinflammation. Z-guggulsterone, a compound extracted from the gum resin of the tree commiphora mukul, exhibits numerous anti-inflammatory effects. However, the role and mechanism of Z-guggulsterone in pro-inflammatory responses in microglia remains unclear. This study addressed this issue in in vitro murine microglia and in vivo neuroinflammation models. Results showed that Z guggulsterone reduced inducible nitric oxide (iNOS) protein expression as well as nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL 6) production in LPS-stimulated BV-2 cells. Z-guggulsterone also reduced the mRNA level of iNOS, TNF-alpha, and IL-6. Mechanistic studies revealed that Z guggulsterone attenuated the LPS-induced degradation of inhibitor kappa B-alpha (IkappaB-alpha) as well as the LPS-induced nuclear translocation of nuclear factor-kappaB (NF-kappaB). Z-guggulsterone, however, failed to reduce the LPS induced increase in NF-kappaB phosphorylation level. These major findings were ascertained in primary microglia where the LPS-induced increases in iNOS expression, NO content, and IkappaB-alpha degradation were diminished by Z guggulsterone treatment. In a mouse model of neuroinflammation, Z-guggulsterone exhibited significant anti-inflammatory effects, which were exemplified by the attenuation of microglial activation and neuroinflammation-induced behavioral abnormalities in Z-guggulsterone-treated mice. Taken together, these studies demonstrate that Z-guggulsterone attenuates the LPS-mediated induction of pro inflammatory factors in microglia via inhibition of IkappaB-alpha-NF-kappaB signals, providing evidence to uncover the potential role of Z-guggulsterone in neuroinflammation-associated disorder therapies. PMID- 26879836 TI - The blockade of GABAA receptors attenuates the inhibitory effect of orexin type 1 receptors antagonist on morphine withdrawal syndrome in rats. AB - The aim of present study was to investigate the involvement of orexin-A neuropeptide in naloxone-induced morphine withdrawal syndrome via modulating neurons bearing GABAA receptors. The locus coeruleus (LC) is a sensitive site for expression of the somatic aspects of morphine withdrawal. Intra-LC microinjection of GABAA receptor agonist attenuates morphine withdrawal signs in rats. Here we studied the influence of LC orexin type 1 receptors blockade by SB-334867 in presence of bicuculline, a GABAA receptor antagonist, on naloxone-induced morphine withdrawal syndrome. Adult male Wistar rats, weighing 250-300 g, were rendered dependent on morphine by subcutaneous (s.c.) injection of increasing morphine doses (6, 16, 26, 36, 46, 56 and 66 mg/kg, 2 ml/kg) at set intervals of 24 h for 7 days. On 8th day, naloxone (3 mg/kg, s.c.) was injected and the somatic signs of morphine withdrawal were evaluated. Intra-LC microinjections (0.2 MUl) of either bicuculline (15 MUM) or SB-334867 (3 mM) or a combination of both chemicals were done immediately before naloxone injection. Intra-LC microinjection of bicuculline (15 MUM) had no significant effect on morphine withdrawal signs, whereas intra-LC microinjection of SB-334867 considerably attenuated morphine withdrawal signs. However, the effect of SB-334867 in attenuating naloxone-induced morphine withdrawal signs was blocked in presence of bicuculline. This finding, for the first time, indicated that orexin-A may participate in expression of naloxone-induced morphine withdrawal syndrome partly through decreasing the activity of neurons bearing GABAA receptors. PMID- 26879837 TI - A hypothesis of couplet molecules and couplet cells in gastric function and an association with Helicobacter pylori. AB - BACKGROUND: Gastrin, from G-cells, and histamine, from enterochromaffin-like (ECL) cells, are two of the hormones that regulate gastric activity. DISCUSSION: It is proposed that the G-cells and the ECL cells are coupled by the couplet molecules gastrin and histamine and by a prior asymmetrical cell division. The gastrin (from G-cells) stimulates the ECL cells to produce and secrete histamine while, in a reciprocal way, this histamine (from ECL cells), stimulates the G cells to produce and secrete gastrin. These molecules would also stimulate cell division - the gastrin would stimulate cell division of ECL cells while histamine would stimulate that of G-cells. A chemical complex of gastrin and histamine is postulated as is also the asymmetric cell divisions of precursor cells to produce the coupled G-cells and ECL cells. CONCLUSION: There is sufficient evidence to support the feasibility of the model in general, but more direct experimental evidence is required to validate the model as applied here to gastric function. PMID- 26879838 TI - Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction. AB - BACKGROUND/PURPOSE: Cancer stem cells (CSCs) are deemed as the driving force of tumorigenesis in oral squamous cell carcinomas (OSCCs). In this study, we investigated the chemotherapeutic effect of sulforaphane, a dietary component from broccoli sprouts, on targeting OSCC-CSCs. METHODS: The effect of sulforaphane on normal oral epithelial cells (SG) and sphere-forming OSCC-CSCs isolated from SAS and GNM cells was examined. ALDH1 activity and CD44 positivity of OSCC-CSCs with sulforaphane treatment was assessed by flow cytometry analysis. In vitro and in vivo tumorigenicity assays of OSCC-CSCs with sulforaphane treatment were presented. RESULTS: We observed that the sulforaphane dose dependently eliminated the proliferation rate of OSCC-CSCs, whereas the inhibition on SG cells proliferation was limited. Cancer stemness properties including self-renewal, CD44 positivity, and ALDH1 activity were also decreased in OSCC-CSCs with different doses of sulforaphane treatment. Moreover, sulforaphane treatment of OSCC-CSCs decreased the migration, invasion, clonogenicity, and in vivo tumorigenicity of xenograghts. Sulforaphane treatment resulted in a dose-dependent increase in the levels of tumor suppressive miR200c. CONCLUSION: These lines of evidence suggest that sulforaphane can suppress the cancer stemness and tumor-initiating properties in OSCC-CSCs both in vitro and in vivo. PMID- 26879839 TI - Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia. AB - BACKGROUND: Friedreich ataxia is an autosomal recessive disease with no available therapy. Clinical trials with erythropoietin in Friedreich ataxia patients have yielded conflicting results, and the long-term effect of the drug remains unknown. METHODS: We designed a double-blind, placebo-controlled, multicenter trial to test the efficacy of epoetin alfa on 56 patients with Friedreich ataxia. The primary endpoint of the study was the effect of epoetin alfa on peak oxygen uptake (VO2 max) at the cardiopulmonary exercise test. Secondary endpoints were frataxin levels in peripheral blood mononuclear cells, improvement in echocardiography findings, vascular reactivity, neurological progression, upper limb dexterity, safety, and quality of life. Epoetin alfa or placebo (1:1 ratio) was administered subcutaneously at a dose of 1200 IU/Kg of body weight every 12 weeks for 48 weeks. RESULTS: A total of 56 patients were randomized; 27 completed the study in the active treatment group, and 26 completed the study in the placebo group[KG1]. VO2 max was not modified after treatment (0.01 [-0.04 to 0.05]; P = .749), as well as most of the secondary endpoint measures, including frataxin. The 9-hole peg test showed a significant amelioration in the treatment group (-17.24 sec. [-31.5 to -3.0]; P = .018). The treatment was safe and well tolerated. CONCLUSIONS: Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26879840 TI - Acid-Base-Triggered Structural Transformation of a Polyoxometalate Core Inside a Dodecahedrane-like Silver Thiolate Shell. AB - Self-assembly of metavanadate and organosilver(I) salts leads to a novel dodecahedrane-like [Ag30 ((t) BuS)20 ](10+) silver(I) thiolate nanocage that tightly wraps an unusual C2h polyoxovanadate anion. The polyoxovanadate core undergoes transformation to a D3d configuration upon acidification, and reverts back to its original C2h structure upon addition of base. Chromism was observed for the silver(I) thiolate cluster during the configurational change of the central polyoxovanadate core; the color of the solution changes reversibly from green to dark yellow. This work represents the first reported example of chromic polyoxometalate-templated silver(I) thiolate shells that respond to external acid base stimuli. It also represents an important advance in providing crystallographic proof that structural transformations occur in a nanoscale core shell cluster. PMID- 26879843 TI - Modelling populations of Lygus hesperus on cotton fields in the San Joaquin Valley of California: the importance of statistical and mathematical model choice. AB - Understanding the population dynamics of herbivorous insects is critical to developing and implementing effective pest control protocols. In the context of inverse problems, we explore the dynamic effects of pesticide treatments on Lygus hesperus, a common pest of cotton in the western United States. Fitting models to field data, we explore the topic of model selection for an appropriate mathematical model and corresponding statistical models, and use techniques including ANOVA-based model comparison tests and residual plot analysis to make the best selections. In addition we explore the topic of data information content: in this example, we are testing the question of whether data, as it is currently collected, can support time-dependent parameter estimation. Furthermore, we investigate the statistical assumptions often haphazardly made in the process of parameter estimation and consider the implications of unfounded assumptions. PMID- 26879842 TI - Treatment of beta amyloid 1-42 (Abeta(1-42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo. AB - In Alzheimer's disease (AD), there is a loss in cholinergic innervation targets of basal forebrain which has been implicated in substantial cognitive decline. Amyloid beta peptide (Abeta(1-42)) accumulates in AD that is highly toxic for basal forebrain cholinergic (BFC) neurons. Although the gonadal steroid estradiol is neuroprotective, the administration is associated with risk of off-target effects. Previous findings suggested that non-classical estradiol action on intracellular signaling pathways has ameliorative potential without estrogenic side effects. After Abeta(1-42) injection into mouse basal forebrain, a single dose of 4-estren-3alpha, 17beta-diol (estren), the non-classical estradiol pathway activator, restored loss of cholinergic cortical projections and also attenuated the Abeta(1-42)-induced learning deficits. Estren rapidly and directly phosphorylates c-AMP-response-element-binding-protein and extracellular-signal regulated-kinase-1/2 in BFC neurons and restores the cholinergic fibers via estrogen receptor-alpha. These findings indicated that selective activation of non-classical intracellular estrogen signaling has a potential to treat the damage of cholinergic neurons in AD. PMID- 26879841 TI - A review of trabecular bone functional adaptation: what have we learned from trabecular analyses in extant hominoids and what can we apply to fossils? AB - Many of the unresolved debates in palaeoanthropology regarding evolution of particular locomotor or manipulative behaviours are founded in differing opinions about the functional significance of the preserved external fossil morphology. However, the plasticity of internal bone morphology, and particularly trabecular bone, allowing it to respond to mechanical loading during life means that it can reveal greater insight into how a bone or joint was used during an individual's lifetime. Analyses of trabecular bone have been commonplace for several decades in a human clinical context. In contrast, the study of trabecular bone as a method for reconstructing joint position, joint loading and ultimately behaviour in extant and fossil non-human primates is comparatively new. Since the initial 2D studies in the late 1970s and 3D analyses in the 1990 s, the utility of trabecular bone to reconstruct behaviour in primates has grown to incorporate experimental studies, expanded taxonomic samples and skeletal elements, and improved methodologies. However, this work, in conjunction with research on humans and non-primate mammals, has also revealed the substantial complexity inherent in making functional inferences from variation in trabecular architecture. This review addresses the current understanding of trabecular bone functional adaptation, how it has been applied to hominoids, as well as other primates and, ultimately, how this can be used to better interpret fossil hominoid and hominin morphology. Because the fossil record constrains us to interpreting function largely from bony morphology alone, and typically from isolated bones, analyses of trabecular structure, ideally in conjunction with that of cortical structure and external morphology, can offer the best resource for reconstructing behaviour in the past. PMID- 26879844 TI - Self-Powered High-Resolution and Pressure-Sensitive Triboelectric Sensor Matrix for Real-Time Tactile Mapping. AB - A triboelectric sensor matrix (TESM) can accurately track and map 2D tactile sensing. A self-powered, high-resolution, pressure-sensitive, flexible and durable TESM with 16 * 16 pixels is fabricated for the fast detection of single point and multi-point touching. Using cross-locating technology, a cross-type TESM with 32 * 20 pixels is developed for more rapid tactile mapping, which significantly reduces the addressing lines from m * n to m + n. PMID- 26879845 TI - Change in Depression Symptomatology and Cognitive Function in Twins: A 10-Year Follow-Up Study. AB - A complex interrelation exists between change in depression symptomatology and cognitive decline. Studies indicate either that depression is a direct risk factor for cognitive change over time, or vice versa. Longitudinal twin studies provide the possibility to unravel cause and effect of correlated traits. Here, we have applied twin modeling approaches to shed light on the genetic correlation between both level and change of depression symptomatology and cognitive functioning, and to further explore the bidirectionality of any such correlation using assessments of both phenotypes at two occasions 10 years apart. The study included 2,866 Danish twins with a mean age of 56.8 years at intake (range: 45-68 years). Of these, 1,267 were intact pairs. A total number of 1,582 twins (55%), of whom 557 were intact pairs, participated in the follow-up survey. We found stable cross-sectional heritability estimates of approximately 60% for general cognitive abilities and 30% for affective depressive symptoms. There was a considerable decline in the mean cognitive performance over 10 years, whereas the mean affective depression symptoms score was stable and with no genetic contribution to any individual change. Additionally, we saw a small but significant cross-trait correlation at both occasions (-0.11 and -0.09, respectively), but cross-trait cross-occasion analysis revealed no evidence that either of the two traits predicts the other over a 10-year interval. Thus, our study was not able to detect any causal association between change in depressive symptomatology and cognitive decline in middle-aged and elderly people over a 10 year interval. PMID- 26879846 TI - Successful treatment outcome of primary melioidosis pneumonia-a case report from Bangladesh. AB - BACKGROUND: Melioidosis is endemic in tropical Australia and Southeast Asian countries and its causative organism Burkholderia pseudomallei is a recognized cause of pneumonia in these regions. Recent isolation of the organism in the soil of Kapasia, Gazipur, Bangladesh has proven its exposure among the population residing in endemic areas of our country. Pneumonia is the most common presentation of melioidosis. Acute, subacute and chronic pneumonia due to B. pseudomallei can present as primary or secondary pneumonia. Treatment of such cases are challenging as well. Till date, few cases of acute and chronic pneumonia due to melioidosis occurring in local Bangladeshis as well as in returning travelers to Europe have been reported. To the best of our knowledge, this is the first reported case of primary melioidosis pneumonia declared cured after a 27 weeks of treatment regimen from Bangladesh. CASE PRESENTATION: A 43 year-old Bangladeshi gentleman, known diabetic, hypertensive, smoker, presented with the complaints of recurrent episodes of low to high grade intermittent fever, productive cough with occasional haemoptysis and 10 kg weight loss over one and half months. Poorly responding to conventional antibiotics, he was suspected as a case of pulmonary tuberculosis. Examination and investigations revealed left sided consolidation with cavitary lesion, hepato-splenomegaly and sputum analysis confirmed growth of Burkholderia pseudomallei. The patient was successfully treated as a case of primary melioidosis pneumonia. CONCLUSION: Often misdiagnosed and empirically treated as tuberculosis, untreated melioidosis pneumonia may even lead to death. Therefore, melioidosis should be suspected in appropriate clinical scenario in patients with a history of residing in or traveling to endemic areas. In Bangladesh, time has come to explore whether melioidosis should be considered as an emerging infectious disease. PMID- 26879847 TI - A nutrient profiling system for the (re)formulation of a global food and beverage portfolio. AB - PURPOSE: To describe the Nestle Nutritional Profiling System (NNPS) developed to guide the reformulation of Nestle products, and the results of its application in the USA and France. DESIGN: The NNPS is a category-specific system that calculates nutrient targets per serving as consumed, based on age-adjusted dietary guidelines. Products are aggregated into 32 food categories. The NNPS ensures that excessive amounts of nutrients to limit cannot be compensated for by adding nutrients to encourage. A study was conducted to measure changes in nutrient profiles of the most widely purchased Nestle products from eight food categories (n = 99) in the USA and France. A comparison was made between the 2009 2010 and 2014-2015 products. RESULTS: The application of the NNPS between 2009 2010 and 2014-2015 was associated with an overall downwards trend for all nutrients to limit. Sodium and total sugars contents were reduced by up to 22 and 31 %, respectively. Saturated Fatty Acids and total fat reductions were less homogeneous across categories, with children products having larger reductions. Energy per serving was reduced by <10 % in most categories, while serving sizes remained unchanged. CONCLUSIONS: The NNPS sets feasible and yet challenging targets for public health-oriented reformulation of a varied product portfolio; its application was associated with improved nutrient density in eight major food categories in the USA and France. Confirmatory analyses are needed in other countries and food categories; the impact of such a large-scale reformulation on dietary intake and health remains to be investigated. PMID- 26879848 TI - Prediction of risk of recurrence of venous thromboembolism following treatment for a first unprovoked venous thromboembolism: systematic review, prognostic model and clinical decision rule, and economic evaluation. AB - BACKGROUND: Unprovoked first venous thromboembolism (VTE) is defined as VTE in the absence of a temporary provoking factor such as surgery, immobility and other temporary factors. Recurrent VTE in unprovoked patients is highly prevalent, but easily preventable with oral anticoagulant (OAC) therapy. The unprovoked population is highly heterogeneous in terms of risk of recurrent VTE. OBJECTIVES: The first aim of the project is to review existing prognostic models which stratify individuals by their recurrence risk, therefore potentially allowing tailored treatment strategies. The second aim is to enhance the existing research in this field, by developing and externally validating a new prognostic model for individual risk prediction, using a pooled database containing individual patient data (IPD) from several studies. The final aim is to assess the economic cost effectiveness of the proposed prognostic model if it is used as a decision rule for resuming OAC therapy, compared with current standard treatment strategies. METHODS: Standard systematic review methodology was used to identify relevant prognostic model development, validation and cost-effectiveness studies. Bibliographic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched using terms relating to the clinical area and prognosis. Reviewing was undertaken by two reviewers independently using pre-defined criteria. Included full-text articles were data extracted and quality assessed. Critical appraisal of included full texts was undertaken and comparisons made of model performance. A prognostic model was developed using IPD from the pooled database of seven trials. A novel internal-external cross-validation (IECV) approach was used to develop and validate a prognostic model, with external validation undertaken in each of the trials iteratively. Given good performance in the IECV approach, a final model was developed using all trials data. A Markov patient-level simulation was used to consider the economic cost-effectiveness of using a decision rule (based on the prognostic model) to decide on resumption of OAC therapy (or not). RESULTS: Three full-text articles were identified by the systematic review. Critical appraisal identified methodological and applicability issues; in particular, all three existing models did not have external validation. To address this, new prognostic models were sought with external validation. Two potential models were considered: one for use at cessation of therapy (pre D-dimer), and one for use after cessation of therapy (post D-dimer). Model performance measured in the external validation trials showed strong calibration performance for both models. The post D-dimer model performed substantially better in terms of discrimination (c = 0.69), better separating high- and low-risk patients. The economic evaluation identified that a decision rule based on the final post D-dimer model may be cost-effective for patients with predicted risk of recurrence of over 8% annually; this suggests continued therapy for patients with predicted risks >= 8% and cessation of therapy otherwise. CONCLUSIONS: The post D-dimer model performed strongly and could be useful to predict individuals' risk of recurrence at any time up to 2-3 years, thereby aiding patient counselling and treatment decisions. A decision rule using this model may be cost-effective for informing clinical judgement and patient opinion in treatment decisions. Further research may investigate new predictors to enhance model performance and aim to further externally validate to confirm performance in new, non-trial populations. Finally, it is essential that further research is conducted to develop a model predicting bleeding risk on therapy, to manage the balance between the risks of recurrence and bleeding. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003494. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26879849 TI - Timing of malaria in pregnancy and impact on infant growth and morbidity: a cohort study in Uganda. AB - BACKGROUND: Malaria in pregnancy (MiP) is a major cause of fetal growth restriction and low birth weight in endemic areas of sub-Saharan Africa. Understanding of the impact of MiP on infant growth and infant risk of malaria or morbidity is poorly characterized. The objective of this study was to describe the impact of MIP on subsequent infant growth, malaria and morbidity. METHODS: Between 2006 and 2009, 82 % (832/1018) of pregnant women with live-born singletons and ultrasound determined gestational age were enrolled in a prospective cohort with active weekly screening and treatment for malaria. Infants were followed monthly for growth and morbidity and received active monthly screening and treatment for malaria during their first year of life. Multivariate analyses were performed to analyse the association between malaria exposure during pregnancy and infants' growth, malaria infections, diarrhoea episodes and acute respiratory infections. RESULTS: Median time of infant follow up was 12 months and infants born to a mother who had MiP were at increased risk of impaired height and weight gain (-2.71 cm, 95 % CI -4.17 to -1.25 and -0.42 kg, 95 % CI -0.76 to -0.08 at 12 months for >1 MiP compared to no MiP) and of malaria infection (relative risk 10.42, 95 % CI 2.64-41.10 for infants born to mothers with placental malaria). The risks of infant growth restriction and infant malaria infection were maximal when maternal malaria occurred in the 12 weeks prior to delivery. Recurrent MiP was also associated with acute respiratory infection (RR 1.96, 95 % CI 1.25-3.06) and diarrhoea during infancy (RR 1.93, 95 % CI 1.02-3.66). CONCLUSION: This study shows that despite frequent active screening and prompt treatment of MiP, impaired growth and an increased risk of malaria and non-malaria infections can be observed in the infants. Effective preventive measures in pregnancy remain a research priority. This study was registered with ClinicalTrials.gov, number NCT00495508. PMID- 26879850 TI - Cross-sectional and longitudinal associations between energy intake and BMI z score in European children. AB - BACKGROUND: Evidence for the effect of dietary energy on BMI z-scores in young children is limited. We aim to investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. METHODS: To investigate cross-sectional and longitudinal effects of daily energy intake (EI) on BMI z-scores of European boys and girls considering growth-related height dependencies of EI using residual EI. METHODS: Subjects were children aged 2- < 10 y old (N = 2753, 48.2% girls) participating in the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) baseline and follow-up examination. Usual EI (kcal/day) was calculated based on the National Cancer Institute-method excluding subjects with implausible reported EI. Effect of age, height and sex-adjusted residuals of EI on BMI z score was investigated stratified by baseline age -group (2- < 4 y, 4- < 6 y, 6- < 8 y and 8- < 10 y) cross-sectionally using linear regression models adjusted for relevant confounders (crude model: age, sex, country; fully adjusted model: plus parental ISCED level, parental BMI, screen time; subgroup analysis: plus objectively measured physical activity). Longitudinal associations were estimated between changes in (Delta) residual EI per year and DeltaBMI z-score per year with adjustments analogously to the cross-sectional models but with additional adjustment for residual EI at baseline. RESULTS: Cross-sectionally, positive associations were observed between residual EI and BMI z-score for the full study sample, for boys and in older (>=6 years) but not in younger children in the crude and fully adjusted model. Longitudinally, small positive associations were observed between Deltaresidual EI per y on DeltaBMI z-score per y for the full study sample and in 4- < 6 y olds in the crude and fully adjusted model. CONCLUSION: In conclusion, EI above the average intakes for a certain sex, age and height are weakly associated with BMI z-scores in European children. Residual EI may be considered as a useful exposure measure in children as it accounts for growth-related changes in usual EI during childhood. PMID- 26879852 TI - Reduced expressions of calmodulin genes and protein and reduced ability of calmodulin to activate plasma membrane Ca(2+)-ATPase in the brain of protein undernourished rats: modulatory roles of selenium and zinc supplementation. AB - The roles of protein undernutrition as well as selenium (Se) and zinc (Zn) supplementation on the ability of calmodulin (CaM) to activate erythrocyte ghost membrane (EGM) Ca(2+)-ATPase and the calmodulin genes and protein expressions in rat's cortex and cerebellum were investigated. Rats on adequate protein diet and protein-undernourished (PU) rats were fed with diet containing 16% and 5% casein, respectively, for a period of 10 weeks. The rats were then supplemented with Se and Zn at a concentration of 0.15 and 227 mg l(-1), respectively, in drinking water for 3 weeks. The results obtained from the study showed significant reductions in synaptosomal plasma membrane Ca(2+)-ATPase (PMCA) activity, Ca(2+)/CaM activated EGM Ca(2+) ATPase activity and calmodulin genes and protein expressions in PU rats. Se or Zn supplementation improved the ability of Ca(2+)/CaM to activate EGM Ca(2+)-ATPase and protein expressions. Se or Zn supplementation improved gene expression in the cerebellum but not in the cortex. Also, the activity of PMCA was significantly improved by Zn. In conclusion, it is postulated that Se and Zn might be beneficial antioxidants in protecting against neuronal dysfunction resulting from reduced level of calmodulin such as present in protein undernutrition. PMID- 26879853 TI - Synthesis of fluorinated carbazoles via C-H arylation catalyzed by Pd/Cu bimetal system and their antibacterial activities. AB - An effective intramolecular C-H arylation reaction catalyzed by a bimetallic catalytic system Pd(OAc)2/CuI for the synthesis of fluorine-substituted carbazoles from corresponding N-phenyl-2-haloaniline derivatives under ligand free conditions is demonstrated. The established method is effective for both N phenyl-2-bromoaniline and N-phenyl-2-chloroaniline, and requires the low loading of Pd(OAc)2 (0.5 mol%). A series of new fluorinated carbazoles were synthesized in excellent yields using the protocol (>83%, 19 examples) and were fully characterized by (1)H, (13)C and (19)F NMR spectral data, HRMS and elemental analysis. All compounds were evaluated for their antibacterial activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and methicillin-resistant S. aureus with resistance to gentamicin) by serial dilution technique. All tested compounds showed antibacterial activity against three test strains (S. aureus, B. subtilis and MRSA), and most of these compounds displayed pronounced antimicrobial activities against these three strains with low MIC values ranging from 0.39 to 6.25 MUg/mL. Among them, compounds 7 and 14 exhibited potent inhibitory activity better than reference drugs meropenem and streptomycin. Three compounds (2, 4 and 5) showed antibacterial activity against E. coli. with MIC values from 12.5 to 25 MUg/mL. PMID- 26879854 TI - Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease. AB - Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity. PMID- 26879855 TI - Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies. AB - Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a-5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 MUM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 MUM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results. PMID- 26879856 TI - Salicylanilide N-monosubstituted carbamates: Synthesis and in vitro antimicrobial activity. AB - The research of innovative antimicrobial agents represents a cutting edge topic. Hence, we synthesized and characterised novel salicylanilide N-monosubstituted carbamates. Twenty compounds were evaluated in vitro against eight bacterial strains and eight fungal species. The lowest minimum inhibitory concentrations (MICs) were found to be ?0.49 MUM. Genus Staphylococcus, including methicillin resistant Staphylococcus aureus, and fungus Trichophyton mentagrophytes showed uniformly the highest rate of susceptibility, whilst Gram-negative bacteria and most of the fungi were less susceptible. A wide range of carbamates provided comparable or superior in vitro antimicrobial activity in comparison to established drugs. Interestingly, extended-spectrum beta-lactamase producing strain of Klebsiella pneumoniae was inhibited with MICs starting from 31.25 MUM. With respect to Staphylococci, 2-[(4-bromophenyl)carbamoyl]-4-chlorophenyl phenylcarbamate exhibited the lowest MIC values (?0.98 MUM). 2-[(4 Bromophenyl)carbamoyl]-4-chlorophenyl benzylcarbamate showed the widest spectrum of antifungal action. The results indicate that some salicylanilide carbamates can be considered to be promising candidates for future investigation. PMID- 26879857 TI - Application of PEG-400 as a green biodegradable polymeric medium for the catalyst free synthesis of spiro-dihydropyridines and their use as acetyl and butyrylcholinesterase inhibitors. AB - A simple, efficient and green approach for the synthesis of spiro dihydropyridines derivatives by one-pot multi-component reaction of isatin or acenaphthoquinone derivatives (1 equiv) with malononitrile (1 equiv) and N,N' substituted-2-nitroethene-1,1-diamines (1 equiv) in PEG-400 under catalyst-free conditions is described. This method provides several advantages such as environmental friendliness, short reaction time, and simple workup procedure for the synthesis of biologically important compounds. The ability of synthesized compounds in inhibition of acetyl and butyrylcholinesterase were investigated both in vitro and in silico. All compounds showed moderate to high level activity against both acetyl and butyrylcholinesterase. There was a good correlation between in vitro and in silico studies. PMID- 26879858 TI - Intramolecular Cyclopropanation of 1,4-Dienes through Hydroboration-Homologation: Easy Access to Bicyclo[3.1.0]hexanes. AB - An intramolecular cyclopropanation reaction involving B-(1 chloroalkyl)catecholborane intermediates generated from 1,4-dienes through hydroboration with catecholborane and Matteson homologation was developed. This sequential procedure leading to bicyclo[3.1.0]hexanes involves the formation of three new sigma C-C bonds at the same carbon atom. A mechanistic study supports the involvement of carbocationic intermediates. PMID- 26879859 TI - An Exploratory Factor Analysis of a Brief Self-Report Scale to Detect Neurocognitive Impairment Among Participants Enrolled in Methadone Maintenance Therapy. AB - The present study examines the factor structure of the existing Neuropsychological Impairment Scale (NIS) through the use of exploratory factor analysis (EFA). The NIS is a brief, self-report measure originally designed to assess neurocognitive impairment (NCI) by having patients rate a range of items that may influence cognitive functioning. Stabilized patients on methadone maintenance therapy (MMT; N=339) in New Haven, CT who reported drug- or sex related HIV risk behaviors in the past 6 months were administered the full 95 item NIS. An EFA was then conducted using principal axis factoring and orthogonal varimax rotation. The EFA resulted in retaining 57 items, with a 9-factor solution that explained 54.8% of the overall variance. The revised 9-factor measure--now referred to as the Brief Inventory of Neuro-cognitive Impairment (BINI)--showed a diverse set of factors with excellent to good reliability (i.e., F1 alpha=0.97 to F9 alpha=0.73). This EFA suggests the potential utility of using the BINI in the context of addiction treatment. Further research should examine the utility of this tool within other clinical care settings. PMID- 26879860 TI - Epidermal thymic stromal lymphopoietin predicts the development of atopic dermatitis during infancy. PMID- 26879861 TI - PKD signaling and pancreatitis. AB - BACKGROUND: Acute pancreatitis is a serious medical disorder with no current therapies directed to the molecular pathogenesis of the disorder. Inflammation, inappropriate intracellular activation of digestive enzymes, and parenchymal acinar cell death by necrosis are the critical pathophysiologic processes of acute pancreatitis. Thus, it is necessary to elucidate the key molecular signals that mediate these pathobiologic processes and develop new therapeutic strategies to attenuate the appropriate signaling pathways in order to improve outcomes for this disease. A novel serine/threonine protein kinase D (PKD) family has emerged as key participants in signal transduction, and this family is increasingly being implicated in the regulation of multiple cellular functions and diseases. METHODS: This review summarizes recent findings of our group and others regarding the signaling pathway and the biological roles of the PKD family in pancreatic acinar cells. In particular, we highlight our studies of the functions of PKD in several key pathobiologic processes associated with acute pancreatitis in experimental models. RESULTS: Our findings reveal that PKD signaling is required for NF-kappaB activation/inflammation, intracellular zymogen activation, and acinar cell necrosis in rodent experimental pancreatitis. Novel small-molecule PKD inhibitors attenuate the severity of pancreatitis in both in vitro and in vivo experimental models. Further, this review emphasizes our latest advances in the therapeutic application of PKD inhibitors to experimental pancreatitis after the initiation of pancreatitis. CONCLUSIONS: These novel findings suggest that PKD signaling is a necessary modulator in key initiating pathobiologic processes of pancreatitis, and that it constitutes a novel therapeutic target for treatments of this disorder. PMID- 26879863 TI - Recent developments in time-of-flight PET. AB - While the first time-of-flight (TOF)-positron emission tomography (PET) systems were already built in the early 1980s, limited clinical studies were acquired on these scanners. PET was still a research tool, and the available TOF-PET systems were experimental. Due to a combination of low stopping power and limited spatial resolution (caused by limited light output of the scintillators), these systems could not compete with bismuth germanate (BGO)-based PET scanners. Developments on TOF system were limited for about a decade but started again around 2000. The combination of fast photomultipliers, scintillators with high density, modern electronics, and faster computing power for image reconstruction have made it possible to introduce this principle in clinical TOF-PET systems. This paper reviews recent developments in system design, image reconstruction, corrections, and the potential in new applications for TOF-PET. After explaining the basic principles of time-of-flight, the difficulties in detector technology and electronics to obtain a good and stable timing resolution are shortly explained. The available clinical systems and prototypes under development are described in detail. The development of this type of PET scanner also requires modified image reconstruction with accurate modeling and correction methods. The additional dimension introduced by the time difference motivates a shift from sinogram- to listmode-based reconstruction. This reconstruction is however rather slow and therefore rebinning techniques specific for TOF data have been proposed. The main motivation for TOF-PET remains the large potential for image quality improvement and more accurate quantification for a given number of counts. The gain is related to the ratio of object size and spatial extent of the TOF kernel and is therefore particularly relevant for heavy patients, where image quality degrades significantly due to increased attenuation (low counts) and high scatter fractions. The original calculations for the gain were based on analytical methods. Recent publications for iterative reconstruction have shown that it is difficult to quantify TOF gain into one factor. The gain depends on the measured distribution, the location within the object, and the count rate. In a clinical situation, the gain can be used to either increase the standardized uptake value (SUV) or reduce the image acquisition time or administered dose. The localized nature of the TOF kernel makes it possible to utilize local tomography reconstruction or to separate emission from transmission data. The introduction of TOF also improves the joint estimation of transmission and emission images from emission data only. TOF is also interesting for new applications of PET-like isotopes with low branching ratio for positron fraction. The local nature also reduces the need for fine angular sampling, which makes TOF interesting for limited angle situations like breast PET and online dose imaging in proton or hadron therapy. The aim of this review is to introduce the reader in an educational way into the topic of TOF-PET and to give an overview of the benefits and new opportunities in using this additional information. PMID- 26879864 TI - CADA-computer-aided DaTSCAN analysis. AB - BACKGROUND: Dopamine transporter (DaT) imaging (DaTSCAN) is useful for the differential diagnosis of parkinsonian syndromes. Visual evaluation of DaTSCAN images represents the generally accepted diagnostic method, but it is strongly dependent on the observer's experience and shows inter- and intra-observer variability. A reliable and automatic method for DaTSCAN evaluation can provide objective quantification; it is desirable for longitudinal studies, and it allows for a better follow-up control. Moreover, it is crucial for an automated method to produce coherent measures related to the severity of motor symptoms. METHODS: In this work, we propose a novel fully automated technique for DaTSCAN analysis that generates quantitative measures based on striatal intensity, shape, symmetry and extent. We tested these measures using a support vector machine (SVM) classifier. RESULTS: The proposed measures reached 100 % accuracy in distinguishing between patients with Parkinson's disease (PD) and control subjects. We also demonstrate the existence of a linear relationship and an exponential trend between pooled structural and functional striatal characteristics and the Unified Parkinson's disease Rating Scale (UPDRS) motor score. CONCLUSIONS: We present a novel, highly reproducible, user-independent technique for DaTSCAN analysis producing quantitative measures directly connected to striatum uptake and shape. In our method, no a priori assumption is required on the spatial conformation and localization of striatum, and both uptake and symmetry contribute to the index quantification. These measures can reliably support a computer-assisted decision system. PMID- 26879862 TI - Evidence-based clinical practice guidelines for peptic ulcer disease 2015. AB - The Japanese Society of Gastroenterology (JSGE) revised the evidence-based clinical practice guidelines for peptic ulcer disease in 2014 and has created an English version. The revised guidelines consist of seven items: bleeding gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non eradication therapy, drug-induced ulcer, non-H. pylori, non-nonsteroidal anti inflammatory drug (NSAID) ulcer, surgical treatment, and conservative therapy for perforation and stenosis. Ninety clinical questions (CQs) were developed, and a literature search was performed for the CQs using the Medline, Cochrane, and Igaku Chuo Zasshi databases between 1983 and June 2012. The guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Therapy is initially provided for ulcer complications. Perforation or stenosis is treated with surgery or conservatively. Ulcer bleeding is first treated by endoscopic hemostasis. If it fails, surgery or interventional radiology is chosen. Second, medical therapy is provided. In cases of NSAID related ulcers, use of NSAIDs is stopped, and anti-ulcer therapy is provided. If NSAID use must continue, the ulcer is treated with a proton pump inhibitor (PPI) or prostaglandin analog. In cases with no NSAID use, H. pylori-positive patients receive eradication and anti-ulcer therapy. If first-line eradication therapy fails, second-line therapy is given. In cases of non-H. pylori, non-NSAID ulcers or H. pylori-positive patients with no indication for eradication therapy, non eradication therapy is provided. The first choice is PPI therapy, and the second choice is histamine 2-receptor antagonist therapy. After initial therapy, maintenance therapy is provided to prevent ulcer relapse. PMID- 26879865 TI - Network stratification analysis for identifying function-specific network layers. AB - A major challenge of systems biology is to capture the rewiring of biological functions (e.g. signaling pathways) in a molecular network. To address this problem, we proposed a novel computational framework, namely network stratification analysis (NetSA), to stratify the whole biological network into various function-specific network layers corresponding to particular functions (e.g. KEGG pathways), which transform the network analysis from the gene level to the functional level by integrating expression data, the gene/protein network and gene ontology information altogether. The application of NetSA in yeast and its comparison with a traditional network-partition both suggest that NetSA can more effectively reveal functional implications of network rewiring and extract significant phenotype-related biological processes. Furthermore, for time-series or stage-wise data, the function-specific network layer obtained by NetSA is also shown to be able to characterize the disease progression in a dynamic manner. In particular, when applying NetSA to hepatocellular carcinoma and type 1 diabetes, we can derive functional spectra regarding the progression of the disease, and capture active biological functions (i.e. active pathways) in different disease stages. The additional comparison between NetSA and SPIA illustrates again that NetSA could discover more complete biological functions during disease progression. Overall, NetSA provides a general framework to stratify a network into various layers of function-specific sub-networks, which can not only analyze a biological network on the functional level but also investigate gene rewiring patterns in biological processes. PMID- 26879866 TI - Cholinergic activation of neurons in the medulla oblongata changes urinary bladder activity by plasma vasopressin release in female rats. AB - The central control of the micturition is dependent on cortical areas and other ascending and descending pathways in the brain stem. The descendent pathways from the pons to the urinary bladder (UB) can be direct or indirect through medullary neurons (MN). Chemical stimulation with l-glutamate of MN known for their involvement in cardiovascular regulation evokes changes in pelvic nerves activities, which innervate the urinary bladder. Different neurotransmitters have been found in medullary areas; nevertheless, their involvement in UB control is few understood. We focused to investigate if cholinergic activation of neurons in the medulla oblongata changes the urinary bladder activity. Carbachol (cholinergic agonist) or atropine (cholinergic antagonist) was injected into the 4thV in anesthetized female Wistar rats and the intravesical pressure (IP), mean arterial pressure (MAP), heart rate (HR) and renal conductance (RC) were recorded for 30 min. Carbachol injection into the 4thV increased IP with peak response at 30 min after carbachol and yielded no changes in MAP, HR and RC. Atropine injection into the 4thV decreased IP and elicited no changes in MAP, HR and RC. Plasma vasopressin levels evaluated by ELISA kit assay increased after carbachol into the 4th V. Intravenous blockade of V1 receptors prior to carbachol into the 4thV abolished the increase in IP evoked by carbachol. Therefore, our findings suggest that cholinergic activation of neurons in the medulla oblongata by carbachol injections into the 4thV increases IP due to plasma vasopressin release, which acts in V1 receptors in the UB. PMID- 26879867 TI - Inhibition of endoplasmic reticulum stress-activated IRE1alpha-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rat model of Parkinson's disease. AB - Telmisartan, one unique angiotensin II type 1 receptor blocker, has been attracting attention due to its putative peroxisome proliferator-activated receptor (PPAR)-gamma or beta/delta actions. Recently, telmisartan has been reported to exert neuroprotective effects in animal models of Parkinson's disease (PD). However, the underlying mechanisms have not been fully clarified. Recently, accumulating evidence has shown that endoplasmic reticulum (ER) stress plays a crucial role in rotenone-induced neuronal apoptosis. Additionally, studies have revealed that inositol-requiring enzyme/endonuclease 1alpha (IRE1alpha) is necessary and sufficient to trigger ER stress. In the present study, we aimed to determine whether ER stress-activated IRE1alpha-mediated apoptotic pathway is involved in the neuroprotection of telmisartan in the rotenone rats of PD and explore the possible involvement of PPAR-beta/delta activation. The catalepsy tests were performed to test the catalepsy symptom. The dopamine content and alpha-synuclein expression were ascertained through high-performance liquid chromatography and immunohistochemistry, respectively. The expression of IRE1alpha, TNF receptor associated factor 2 (TRAF2), caspase-12 and PPAR beta/delta was detected by western blot. Neuronal apoptosis was assessed by TUNEL and immunohistochemistry. Our results show that telmisartan ameliorated the catalepsy symptom and attenuated dopamine depletion as well as alpha-synuclein accumulation. Moreover, telmisartan decreased ER stress-mediated neuronal apoptosis. Furthermore, telmisartan inhibited IRE1alpha-TRAF2-caspase-12 apoptotic signaling pathway. Additionally, telmisartan activated PPAR beta/delta, implying that PPAR-beta/delta activation properties of telmisartan are possibly or partially involved in the neuroprotective effects. In conclusion, our findings suggest that suppressing ER stress-activated IRE1alpha-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rats of PD. PMID- 26879868 TI - Ghrelin induces colon cancer cell proliferation through the GHS-R, Ras, PI3K, Akt, and mTOR signaling pathways. AB - Colon cancer is the third most common malignancy worldwide. Recently, some interesting associations between ghrelin and cancer were reported, and it may participate in colon cancer development. In the present report, we explored the role of the growth hormone secretagogue receptor (GHS-R), Ras, phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) pathways in the ghrelin-induced proliferation of human colon cancer cells. Ghrelin-caused HT-29 proliferation was reduced by [D-Lys3]-GHRP-6 (a GHS-R inhibitor). We also found that a dominant negative mutant of Ras (Ras DN), a PI3K inhibitor (LY 294002), an Akt DN, and an mTOR inhibitor (rapamycin) attenuated ghrelin-caused colon cancer cell proliferation. We found that ghrelin induced time-dependent increases in Ras activity. Moreover, ghrelin-mediated Akt Ser473 phosphorylation was attenuated by a Ras DN and LY 294002. Furthermore, a Ras DN, LY 294002, and an Akt DN all inhibited ghrelin-caused mTOR Ser2448 phosphorylation. These results indicate that the Ras/PI3K/Akt/mTOR cascade plays a critical role in ghrelin-induced colon cancer cell proliferation. PMID- 26879869 TI - Celecoxib enhanced the cytotoxic effect of cisplatin in chemo-resistant gastric cancer xenograft mouse models through a cyclooxygenase-2-dependent manner. AB - Our previous study suggested that co-administration of celecoxib increased chemo sensitivity of multidrug-resistant human gastric cancer SGC-7901/DDP cells to cisplatin (DDP) in vitro. The present study was designed to investigate whether celecoxib had the similar activities in vivo. SGC-7901/DDP and SGC-7901 xenograft mouse models were established. At the end of the experiment, cisplatin treatment alone significantly inhibited tumor growth in SGC-7901 xenograft, as compared with that in SGC-7901/DDP xenograft, suggesting that it maintained cisplatin sensitivity. When cisplatin and celecoxib were co-administrated, their antitumor activities were augmented in SGC-7901/DDP xenograft. The levels of Ki67 and PCNA after combination therapy were significantly decreased in SGC-7901/DDP xenograft, as compared with those of cisplatin treatment alone. Moreover, examining the apoptotic index by TUNEL assay showed similar results. Further studies demonstrated the inhibitory effect of celecoxib on cyclooxygenase-2 and P glycoprotein expression was the possible reason to increase sensitivity of SGC 7901/DDP cells to cisplatin in vivo. However, the ratio of thromboxane B2 and prostaglandin F1alpha was elevated after celecoxib treatment in mice. This has been proposed to increase the risk of thrombogenesis. Further studies are required to evaluate the efficacy and safety of celecoxib for reducing chemo resistance in gastric cancer. PMID- 26879870 TI - Cis-vaccenic acid induces differentiation and up-regulates gamma globin synthesis in K562, JK1 and transgenic mice erythroid progenitor stem cells. AB - Gamma globin induction remains a promising pharmacological therapeutic treatment mode for sickle cell anemia and beta thalassemia, however Hydroxyurea remains the only FDA approved drug which works via this mechanism. In this regard, we assayed the gamma-globin inducing capacity of Cis-vaccenic acid (CVA). CVA induced differentiation of K562, JK1 and transgenic mice primary bone marrow hematopoietic progenitor stem cells. CVA also significantly up-regulated gamma globin gene expression in JK-1 and transgenic mice bone marrow erythroid progenitor stem cells (TMbmEPSCs) but not K562 cells without altering cell viability. Increased gamma-globin expression was accompanied by KLF1 suppression in CVA induced JK-1 cells. Erythropoietin induced differentiation of JK-1 cells 24h before CVA induction did not significantly alter CVA induced differentiation and gamma-globin expression in JK-1 cells. Inhibition of JK-1 and Transgenic mice bone marrow erythroid progenitor stem cells Fatty acid elongase 5 (Elovl5) and Delta(9) desaturase suppressed the gamma-globin inductive effects of CVA. CVA treatment failed to rescue gamma-globin expression in Elovl5 and Delta(9) desaturase inhibited cells 48 h post inhibition in JK-1 cells. The data suggests that CVA directly modulates differentiation of JK-1 and TMbmEPSCs, and indirectly modulates gamma-globin gene expression in these cells. Our findings provide important clues for further evaluations of CVA as a potential fetal hemoglobin therapeutic inducer. PMID- 26879871 TI - Does depression diagnosis and antidepressant prescribing vary by location? Analysis of ethnic density associations using a large primary-care dataset. AB - BACKGROUND: Studies have linked ethnic differences in depression rates with neighbourhood ethnic density although results have not been conclusive. We looked at this using a novel approach analysing whole population data covering just over one million GP patients in four London boroughs. METHOD: Using a dataset of GP records for all patients registered in Lambeth, Hackney, Tower Hamlets and Newham in 2013 we investigated new diagnoses of depression and antidepressant use for: Indian, Pakistani, Bangladeshi, black Caribbean and black African patients. Neighbourhood effects were assessed independently of GP practice using a cross classified multilevel model. RESULTS: Black and minority ethnic groups are up to four times less likely to be newly diagnosed with depression or prescribed antidepressants compared to white British patients. We found an inverse relationship between neighbourhood ethnic density and new depression diagnosis for some groups, where an increase of 10% own-ethnic density was associated with a statistically significant (p < 0.05) reduced odds of depression for Pakistani [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.70-0.93], Indian (OR 0.88, CI 0.81-0.95), African (OR 0.88, CI 0.78-0.99) and Bangladeshi (OR 0.94, CI 0.90 0.99) patients. Black Caribbean patients, however, showed the opposite effect (OR 1.26, CI 1.09-1.46). The results for antidepressant use were very similar although the corresponding effect for black Caribbeans was no longer statistically significant (p = 0.07). CONCLUSION: New depression diagnosis and antidepressant use was shown to be less likely in areas of higher own-ethnic density for some, but not all, ethnic groups. PMID- 26879872 TI - CCR9 in cancer: oncogenic role and therapeutic targeting. AB - Cancer is currently one of the leading causes of death worldwide and is one of the most challenging major public health problems. The main challenges faced by clinicians in the management and treatment of cancer mainly arise from difficulties in early diagnosis and the emergence of tumor chemoresistance and metastasis. The structures of chemokine receptor 9 (CCR9) and its specific ligand chemokine ligand 25 (CCL25) have been elucidated, and, interestingly, a number of studies have demonstrated that CCR9 is a potential tumor biomarker in diagnosis and therapy, as it has been found to be highly expressed in a wide range of cancers. This expression pattern suggests that CCR9 may participate in many important biological activities involved in cancer progression. Researchers have shown that CCR9 that has been activated by its specific ligand CCL25 can interact with many signaling pathways, especially those involved in tumor chemoresistance and metastasis. This review, therefore, focuses on CCR9 induction activity and summarizes what is currently known regarding its role in cancers and its potential application in tumor-targeted therapy. PMID- 26879873 TI - Botulinum Toxin: Pharmacology and Therapeutic Roles in Pain States. AB - Botulinum toxin, also known as Botox, is produced by Clostridium botulinum, a gram-positive anaerobic bacterium, and botulinum toxin injections are among the most commonly practiced cosmetic procedures in the USA. Although botulinum toxin is typically associated with cosmetic procedures, it can be used to treat a variety of other conditions, including pain. Botulinum toxin blocks the release of acetylcholine from nerve endings to paralyze muscles and to decrease the pain response. Botulinum toxin has a long duration of action, lasting up to 5 months after initial treatment which makes it an excellent treatment for chronic pain patients. This manuscript will outline in detail why botulinum toxin is used as a successful treatment for pain in multiple conditions as well as outline the risks associated with using botulinum toxin in certain individuals. As of today, the only FDA-approved chronic condition that botulinum toxin can be used to treat is migraines and this is related to its ability to decrease muscle tension and increase muscle relaxation. Contraindications to botulinum toxin treatments are limited to a hypersensitivity to the toxin or an infection at the site of injection, and there are no known drug interactions with botulinum toxin. Botulinum toxin is an advantageous and effective alternative pain treatment and a therapy to consider for those that do not respond to opioid treatment. In summary, botulinum toxin is a relatively safe and effective treatment for individuals with certain pain conditions, including migraines. More research is warranted to elucidate chronic and long-term implications of botulinum toxin treatment as well as effects in pregnant, elderly, and adolescent patients. PMID- 26879874 TI - New Pain Management Options for the Surgical Patient on Methadone and Buprenorphine. AB - Perioperative management of patients receiving opioid addiction therapy presents a unique challenge for the anesthesiologist. The goal of pain management in this patient population is to effectively manage postoperative pain, to improve patient satisfaction and outcomes, and to reduce the cost of health care. Multimodal analgesics, including nonsteroid anti-inflammatory drugs, intravenous acetaminophen, gabapentanoid agents, and low-dose ketamine infusions, have been used to improve postoperative pain and to reduce postoperative opioid use. Patients on long-term opioid management therapy with methadone and buprenorphine require special considerations. Recommendations and options for treating postoperative pain in patients on methadone and buprenorphine are outlined below. Other postoperative pain management options include patient-controlled analgesia, intravenous, and transdermal, in addition to neuraxial and regional anesthesia techniques. Special patient populations include the parturient on long-term opioid therapy. Recommendations for use of opioids in these patients during labor and delivery and in the postpartum period are discussed. PMID- 26879875 TI - Post-herpetic Neuralgia: a Review. AB - Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients. PMID- 26879876 TI - Perioperative Pain Control in the Ambulatory Setting. AB - Across the USA and various parts of the world, ambulatory surgery centers have transitioned to accepting patients with advanced ASA statuses, leading to a larger volume and higher complexity of surgeries performed, while still urging for same-day patient discharges. Inadequate postoperative pain management and opioid analgesia side effects, such as sedation, respiratory depression, and postoperative nausea and vomiting, are the most common complications and most common reasons for readmission after ambulatory surgery. The trend to limiting these complications and achieve a more rapid patient discharge currently emphasizes a multifactorial, balanced analgesia strategy. This article reviews the multimodal approach by detailing the important aspects of specific regional nerve blocks, nerve blockade with catheter techniques, acetaminophen, non selective NSAIDs, Cox-2 inhibitors, membrane stabilizers, and corticosteroids. Pain management in the ambulatory surgery patient will thus be optimized with a thorough preoperative evaluation, recognizing intraoperative events, and implementing multiple analgesic modalities. PMID- 26879877 TI - Red Ear Syndrome. AB - The Red Ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20 years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, but they can occur in association with primary headaches, including in particular migraine in the developmental age. Although the underlying pathophysiological mechanisms are still uncertain, in the recent years the described comorbidities have aroused increasing interest because of possible clinical implications. Moreover, RES seems to be more often associated with clinical features of migraine partially provoked by the involvement of the parasympathetic system. This clinical association has shed new light on the pathophysiology of RES, supporting the hypothesis of a shared pathophysiological background, for example, through the activation of the trigeminal autonomic reflex. Current therapies of RES will be also discussed. Finally, we will resume the more controversial aspects of this relatively new and probably underestimated neurological syndrome. PMID- 26879878 TI - Headache and Facial Pain in Sickle Cell Disease. AB - Children and adolescents with sickle cell disease (SCD) have a high prevalence of recurrent headaches (24.0-43.9 %). Acute presentation with headache can be diagnostically challenging, as the clinician must consider evaluation of several potentially devastating conditions including vascular diseases (stroke, hemorrhage, venous sinus thrombosis, moyamoya, posterior reversible encephalopathy syndrome), facial and orbital bone infarcts, dental pain, and osteomyelitis. Patients with SCD and primary headache disorders may benefit from comprehensive headache treatment plans that include abortive therapy, prophylactic therapy, and non-pharmacological modalities. Although there is limited data in adults, those with SCD are at risk for medication overuse headache secondary to frequent opioid use. Addressing headache in patients with SCD may help to reduce their use of opioids and disability and improve pain and quality of life. PMID- 26879879 TI - [Prevalence and complications of MRI scans of cochlear implant patients: German version]. AB - BACKGROUND: Cochlear implants (CI) are the preferred method of treatment for patients with severe to profound bilateral sensorineural hearing loss and unilateral deafness. For many years, because of the magnetic field during magnetic resonance imaging (MRI) examinations, MRI examinations were contraindicated for CI patients or feasible only under specific circumstances. MRI examinations of CI recipients entail complications and therefore preventive measures have to be considered. The aim of this study was to evaluate the incidence of MRI scans in CI recipients and the occurrence of complications, and furthermore to investigate the preventive measures taken in radiological daily routine. MATERIALS AND METHODS: A retrospective questionnaire was sent to 482 patients that received CIs from 1999-2013. Details of the MRI examination and subjective and objective incidents during and after the MRI scan were evaluated. RESULTS: A total of 204 CI recipients answered the retrospective questionnaire (42.3%). Twenty patients (9.8%) with 23 implants underwent a total of 33 MRI scans with their cochlear implant in place. In 16 cases the scanned region was the head (49%). Preventive measures in the form of head bandages were taken in 20 cases (61%). The most common complication was pain in 23 cases (70%) and the most serious complication was the dislocation of the internal magnet in 3 cases (9%). CONCLUSIONS: The number of CI recipients undergoing MRI scans is quite high. Possible complications and preventive measures attract too little attention in radiological daily routine. PMID- 26879880 TI - [Specific anosmia as a principle of olfactory perception]. AB - Specific anosmia, the inability to perceive a specific odor, while olfactory perception is otherwise intact, is known as a rather seldom phenomenon. By testing the prevalence of specific anosmia to 20 different odors in a sample of 1600 people, we were able to estimate the general prevalence of anosmia. This revealed that specific anosmia is not rare at all. In contrast, the general likelihood for specific anosmia approaches 1. In addition, specific anosmia can be very well reversed by "smell training" during the course of 3 months. To summarize, specific anosmia seems to be a rule, not an exception, of olfactory sensation. The lack of perception of certain odors may constitute a flexible peripheral filter mechanism, which can be adapted by exposure to odors. PMID- 26879881 TI - Successful infection control for a vancomycin-intermediate Staphylococcus aureus outbreak in an advanced emergency medical service centre. AB - BACKGROUND: A vancomycin-intermediate Staphylococcus aureus (VISA) (vancomycin minimum inhibitory concentration: 4mg/L) outbreak occurred in an advanced emergency medical service centre [hereafter referred to as the intensive care unit (ICU)] between 2013 and 2014. AIM: Our objective was to evaluate the infection control measures that were successful. METHODS: Seventeen VISA strains were isolated from the sputum of 15 inpatients and the skin of two inpatients. Fourteen VISA strains were recognized as colonization. However, three VISA strains were isolated from the sputum of three inpatients with pneumonia. Environmental cultures were performed and VISA strains were detected in five of 65 sites. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) was performed on 21 VISA strains. FINDINGS: Molecular typing including PFGE and MLST showed that the patterns of 19 VISA strains were identical and those of the other two VISA strains were possibly related. This meant that a horizontal transmission of VISA strains had occurred in the ICU. In August 2013, the infection control team began interventions. However, new inpatients with VISA strains continued to appear. Therefore, in October 2013, the ICU was partially closed in order to try to prevent further horizontal transmission, and existing inpatients with the VISA strain were isolated. Although new cases quickly dissipated after the partial closure, it took approximately five months to eradicate the VISA outbreak. CONCLUSION: Our data suggest that despite the employment of various other infection control measures, partial closure of the ICU was essential in terminating this VISA outbreak. PMID- 26879882 TI - Length time bias in surveillance for hepatocellular carcinoma and how to avoid it. AB - AIM: Length time bias is a selection bias which can lead to an overestimation of survival of screening-detected cases caused by the relative excess of slower growing tumors detected with respect to symptomatic cases. This leads to the incorrect perception that screening improves outcomes when it only selects tumors with a favorable biology. Data regarding this bias in surveillance for hepatocellular carcinoma (HCC) have never been provided. METHODS: A semi-Markov model was developed to investigate this issue. An exponential tumor growth was applied. During its growth, tumor diagnosis "at surveillance appointments" was made when tumor attained a size equal to or above the size of tumors diagnosed in surveilled patients obtained from pertinent published reports, or "in-between appointments" (due to the development of symptoms) if tumor size attained the size of symptomatic diagnosis, derived from published reports; otherwise the tumor continued to grow until the time horizon had been reached. Tumor doubling time (DT) values were recorded according to the method of diagnosis. RESULTS: In a theoretical cohort of 1000 patients submitted to semiannual surveillance, 72.5% will be diagnosed at a surveillance appointment and 18% because of symptom development, although under surveillance. Patients diagnosed with HCC at a surveillance appointment had a median tumor DT of 100 days (interquartile range, 68-143 days), whereas those diagnosed because of symptoms had a median DT of 42 days (interquartile range, 29-58 days) although under surveillance. CONCLUSION: The surveillance propensity to detect slower-growth tumors is relevant, and practical suggestions to minimize this bias in longitudinal studies are provided. PMID- 26879883 TI - A little trick to make inside out vein graft technique easier in experimental animal models. PMID- 26879884 TI - Selectivity Effects in Bimetallic Catalysis. AB - An emerging area of homogeneous catalysis is the use of catalysts featuring two closely associated metal sites. This approach complements the traditional focus on single-site catalysts and makes available new parameters with which to optimize catalytic behavior. Single-site catalysts are optimized through changing 1) the identity of the metal, and 2) the steric and electronic properties of the ligands. Bimetallic catalysts introduce new optimization parameters such as 3) catalyst nuclearity (mononuclear vs. binuclear), and 4) bimetallic pairing (relative compatibility of two metal sites). In order to harness these new optimization parameters in developing systems, it is necessary to first understand the origin of bimetallic selectivity effects that already have been documented. This Concept article highlights bimetallic effects on the chemo-, regio-, and stereoselectivity of catalytic transformations, using selected case studies from the recent literature as illustrative examples. PMID- 26879885 TI - Difficulties in using interpreters in clinical encounters as experienced by immigrants living in Sweden. AB - AIMS AND OBJECTIVES: To study a group of immigrants' experiences regarding interactions with primary health care through an interpreter. BACKGROUND: Approximately, 230 million people are resettled outside of their own home country. Thus, more than 3% of the world's population are migrants. It is a major challenge for health care providers to satisfy immigrants' needs for individualised health care services. DESIGN: Qualitative study. METHODS: Focus group interviews were conducted with four groups of immigrants (n = 24) from Bosnia and Herzegovina, Croatia, Kosovo and Somalia. The group interviews were audio recorded, transcribed and analysed, and the text was categorised using the content analysis method. RESULTS: Participants' expectations of the interpreter mediated consultations were high, but not always fulfilled. Interpreters being late, lacking professionalism or lacking knowledge in medical terminology and the use of health care professionals or relatives as interpreters were some of the problems raised. CONCLUSION: A well-organised, disciplined interpreter service with professional and competent interpreters is needed to overcome problems regarding clinical consultations involving interpreters. A satisfactory language bridge has a significant impact on the quality of communications. CLINICAL IMPLICATION: Interpreter services should be well organised, and interpreters should be linguistically, culturally and socially competent, as these factors may have a significant impact on consultation outcomes. Using relatives or staff as interpreters can sometimes be a solution but often results in an unsatisfactory clinical consultation. PMID- 26879886 TI - A common variant association study reveals novel susceptibility loci for low HDL cholesterol levels in ethnic Arabs. AB - The genetic susceptibility to acquiring low high density lipoprotein-cholesterol (LHDLC) levels is not completely elucidated yet. In this study, we performed a common variant association study for harboring this trait in ethnic Arabs. We employed the Affymetrix high-density Axiom Genome-Wide ASI Array (Asian population) providing a coverage of 598,000 single nucleotide variations (SNPs) to genotype 5495 individuals in a two-phase study involving discovery and validation sets of experiments. The rs1800775 [1.31 (1.22-1.42); p = 3.41E-12] in the CETP gene and rs359027 [1.26 (1.16-1.36); p = 2.55E-08] in the LMCD1 gene were significantly associated with LHDLC levels. Furthermore, rs3104435 [1.26 (1.15-1.38); p = 1.19E-06] at the MATN1 locus, rs9835344 [1.16 (1.08-1.26); p = 8.75E-06] in the CNTN6 gene, rs1559997 [1.3 (1.14-1.47); p = 9.48E-06] in the SDS gene and rs1670273 [1.2 (1.1-1.31); p = 4.81E-06] in the DMN/SYNM gene exhibited suggestive association with the disorder. Seven other variants including rs1147169 in the PLCL1 gene, rs10248618 in the DNAH11, rs476155 in the GLIS3, rs7024300 in the ABCA1, intergenic rs10836699, rs11603691 in P2RX3 and rs750134 in CORO1C gene exhibited borderline protective properties. Validation and joint meta-analysis resulted in rs1800775, rs3104435 and rs359027 retaining their predisposing properties, while rs10836699 and rs11603691 showed protective properties. Our data show several predisposing variants across the genome for LHDLC levels in ethnic Arabs. PMID- 26879887 TI - Niclosamide inhibits leaf blight caused by Xanthomonas oryzae in rice. AB - Rice leaf blight, which is caused by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), results in huge losses in grain yield. Here, we show that Xoo induced rice leaf blight is effectively controlled by niclosamide, an oral antihelminthic drug and molluscicide, which also functions as an anti-tumor agent. Niclosamide directly inhibited the growth of the three Xoo strains PXO99, 10208 and K3a. Niclosamide moved long distances from the site of local application to distant rice tissues. Niclosamide also increased the levels of salicylate and induced the expression of defense-related genes such as OsPR1 and OsWRKY45, which suppressed Xoo-induced leaf wilting. Niclosamide had no detrimental effects on vegetative/reproductive growth and yield. These combined results indicate that niclosamide can be used to block bacterial leaf blight in rice with no negative side effects. PMID- 26879888 TI - Analysis of Skeletal Muscle Torque Capacity and Circulating Ceramides in Patients with Advanced Heart Failure. AB - BACKGROUND: Heart failure (HF)-related exercise intolerance is thought to be perpetuated by peripheral skeletal muscle functional, structural, and metabolic abnormalities. We analyzed specific dynamics of muscle contraction in patients with HF compared with healthy, sedentary controls. METHODS: Isometric and isokinetic muscle parameters were measured in the dominant upper and lower limbs of 45 HF patients and 15 healthy age-matched controls. Measurements included peak torque normalized to body weight, work normalized to body weight, power, time to peak torque, and acceleration and deceleration to maximum strength times. Body morphometry (dual energy X-ray absorptiometry scan) and circulating fatty acids and ceramides (lipodomics) were analyzed in a subset of subjects (18 HF and 9 controls). RESULTS: Extension and flexion time-to-peak torque was longer in the lower limbs of HF patients. Furthermore, acceleration and deceleration times in the lower limbs were also prolonged in HF subjects. HF subjects had increased adiposity and decreased lean muscle mass compared with controls. Decreased circulating unsaturated fatty acids and increased ceramides were found in subjects with HF. CONCLUSIONS: Delayed torque development suggests skeletal muscle impairments that may reflect abnormal neuromuscular functional coupling. These impairments may be further compounded by increased adiposity and inflammation associated with increased ceramides. PMID- 26879889 TI - Activated learning; providing structure in global health education at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA)- a pilot study. AB - BACKGROUND: Global health rotations are increasingly popular amongst medical students. The training abroad is highly variable and there is a recognized need for global health curriculum development. We sought to create and evaluate a curriculum, applicable to any global health rotation, that requires students to take an active role in their education and promotes engagement. METHODS: Prospective, observational, mixed method study of 4th year medical students enrolled in global health courses at UCLA in 2011-12. Course directors identified 4 topics common to all rotations (traditional medicine, health systems, limited resources, pathology) and developed activities for students to complete abroad: observation, interview and reflection on resources, pathology, medical practices; and compare/contrast their experience with the US healthcare system. Students posted responses on a discussion board moderated by US faculty. After the rotation, students completed an anonymous internet-based evaluative survey. Responses were tabulated. Qualitative data from discussion board postings and free response survey items were analyzed using the framework method. RESULTS: 14 (100 %) students completed the Activated Learning assignment. 12 submitted the post rotation survey (85.7 %). Activated Learning enhanced GH education for 67 % and facilitated engagement in the local medical culture for 67 %. Qualitative analysis of discussion board posting demonstrated multiple areas of knowledge gain and analysis of free response survey items revealed 5 major themes supporting Activated Learning: guided learning, stimulation of discussion, shared interactions, cultural understanding, and knowledge of global healthcare systems. Increased interactivity emerged as the major theme for future improvement. CONCLUSION: The results of this study suggest that an Activated Learning program may enhance education, standardize curricular objectives across multiple sites and promote engagement in local medical culture, pathology and delivery systems. Increased interaction between students and faculty may augment the impact of such a program. PMID- 26879890 TI - Curettage with cement augmentation of large bone defects in giant cell tumors with pathological fractures in lower-extremity long bones. AB - BACKGROUND: Thorough curettage and cement augmentation is the procedure of choice for treating giant cell tumor lesions, particularly those associated with large defects. Its association with pathological fractures has not been studied to a great extent, although a pathological fracture following a giant cell tumor is not a contraindication to treatment by curettage and cementation. We present our experience of bone cementation following intralesional curettage for treatment of giant cell tumors of the long bones of lower limbs with associated pathological fractures. MATERIALS AND METHODS: A total of 38 patients who had undergone a procedure in the weight-bearing long bones of lower limbs were included in the study. The age of the patients ranged from 18-79 years with a mean age of 38.57 years. The average follow-up was 102.42 months (8.5 years) ranging from 60-186 months (5-15.5 years). Results were based on serial radiographs showing consolidation of the lesion along with a subjective clinical examination and Enneking functional evaluation noted in the patient's records. RESULTS: Approximately 76 % of the lesions occurred around the knee. The results were graded as excellent (72 %), good (12.82 %) fair (10.25 %) and poor (5.12 %). Four cases developed a recurrence. Apart from a few documented complications, the lesions showed good consolidation and healed well. CONCLUSION: Giant cell tumors of the long bones of lower limbs with an associated pathological fracture at diagnosis can be managed with thorough curettage and cement augmentation of the bone defect with a satisfactory outcome. LEVEL OF EVIDENCE: Level IV. PMID- 26879891 TI - Alternaria keratitis after uneventful phacoemulsification in an otherwise healthy adult. AB - BACKGROUND: Fungal infections of self-sealing corneal incisions in cataract surgery are scarce. We report a case of Alternaria keratitis, several weeks after uneventful clear-cornea phacoemulsification. FINDINGS: A 42-year-old woman, with a history of retinitis pigmentosa, complained of painful red right eye, 45 days after uneventful self-sealing clear-cornea phacoemulsification. Slit-lamp examination revealed multiple snow-like contiguous stromal infiltrates, with irregular margins, and no epithelial defect. These infiltrates were unresponsive to topical quinolones and topical corticosteroids as well as oral valaciclovir. Culture from corneal biopsy specimen grew Alternaria species. Management consisted of topical amphotericin-B, and then a combination of topical and oral voriconazole. The corneal infiltrates progressively healed. One year later, the best-corrected visual acuity was 20/400. CONCLUSIONS: Fungal infection, particularly Alternaria keratitis, should be considered in the differential diagnosis of delayed post-cataract surgery keratitis. Prompt diagnosis and management are mandatory to improve visual prognosis. PMID- 26879892 TI - Earth's oldest mantle fabrics indicate Eoarchaean subduction. AB - The extension of subduction processes into the Eoarchaean era (4.0-3.6 Ga) is controversial. The oldest reported terrestrial olivine, from two dunite lenses within the ~3,720 Ma Isua supracrustal belt in Greenland, record a shape preferred orientation of olivine crystals defining a weak foliation and a well defined lattice-preferred orientation (LPO). [001] parallel to the maximum finite elongation direction and (010) perpendicular to the foliation plane define a B type LPO. In the modern Earth such fabrics are associated with deformation of mantle rocks in the hanging wall of subduction systems; an interpretation supported by experiments. Here we show that the presence of B-type fabrics in the studied Isua dunites is consistent with a mantle origin and a supra-subduction mantle wedge setting, the latter supported by compositional data from nearby mafic rocks. Our results provide independent microstructural data consistent with the operation of Eoarchaean subduction and indicate that microstructural analyses of ancient ultramafic rocks provide a valuable record of Archaean geodynamics. PMID- 26879893 TI - The effects of a pro-active integrated care intervention for frail community dwelling older people: a quasi-experimental study with the GP-practice as single entry point. AB - BACKGROUND: This study explored the effectiveness of a pro-active, integrated care model for community-dwelling frail older people compared to care as usual by evaluating the effects on a comprehensive set of outcomes: health outcomes (experienced health, mental health and social functioning); functional abilities; and quality of life (general, health-related and well-being). METHODS: The design of this study was quasi-experimental. In this study, 184 frail older patients of three GP practices that implemented the Walcheren Integrated Care Model were compared with 193 frail older patients of five GP practices that provided care as usual. In the Walcheren Integrated Care Model, community-dwelling elderly were pro-actively screened for frailty from the GP practice using the Groningen Frailty Indicator, and care needs were assessed with the EASYcare instrument. The GP practice functioned as single entry point from which case management was provided, and the GP was the coordinator of care. The entire process was supported by multidisciplinary meetings, multidisciplinary protocols and web based patient files. The outcomes of this study were obtained at baseline, after 3 months and after 12 months and analyzed with linear mixed models of repeated measures. RESULTS: The Walcheren Integrated Care Model had a positive effect on love and friendship and a moderately positive effect on general quality of life. The ability to receive love and friendship and general quality of life decreased in the control group but was preserved in the experimental group. No significant differences were found on health outcomes such as experienced health, mental health, social functioning and functional abilities. CONCLUSIONS: The results indicated that pro-active, integrated care can be beneficial for frail older people in terms of quality of life and love and friendship but not in terms of health outcomes and functional abilities. Recommendations for future research are to gain greater insight into what specific outcomes can be achieved with proactive and integrated care, considering the specific content of this care, and to allow for the heterogeneity of frail older people in evaluation research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05748494. Registration date: 14/03/2013. PMID- 26879894 TI - Guest editorial: Efficacious and effective preventive interventions to tackle cyberbullying in the school environment. PMID- 26879895 TI - Effects of the cyberbullying prevention program media heroes (Medienhelden) on traditional bullying. AB - There is considerable debate over whether cyberbullying is just another form of bullying, or whether it is a problem distinct enough to require specific intervention. One way to explore this issue is to analyze whether programs designed to prevent traditional bullying help prevent cyberbullying, and whether programs designed to prevent cyberbullying prevent traditional bullying. The main goal of the current study was to analyze the spillover effects of the cyberbullying prevention program Media Heroes (Medienhelden) on traditional bullying. Media Heroes promotes empathy, knowledge of risks and consequences, and strategies that allow bystanders to defend victims from cyberbullying. Mixed ANOVAs were conducted comparing pretest and post-test (6 months after intervention) measures of 722 students (ages 11-17) assigned to a long (15 sessions) intervention, a short (1 day) intervention, and a control group. In addition to confirming the previously reported effects on cyberbullying, Media Heroes was found to reduce traditional bullying. Effects were larger for the long version of the program than for the short 1-day version. No effects were found on victimization by either cyberbullying or traditional bullying. Strategies to complement traditional and cyberbullying prevention efforts are discussed. Aggr. Behav. 42:157-165, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26879896 TI - Effectiveness and sustainability of the ViSC Social Competence Program to prevent cyberbullying and cyber-victimization: Class and individual level moderators. AB - We investigated whether the general anti-bullying program ViSC sustainably prevents cyberbullying and cyber-victimization. A longitudinal randomized control group design was used to examine (i) program effectiveness immediately after a 1 year implementation phase and (ii) sustainable program effects 6 months later taking several moderators on the class level (class climate and ethnic diversity) and on the individual level (gender, age, internet usage, traditional bullying/victimization) into account. Effectiveness (e.g., the change between waves 2 and 1) was examined in 2,042 students (47.6% girls), aged 11.7 years (SD = 0.88) enrolled in 18 schools and 103 classes. Sustainability (e.g., the change between waves 3 and 2) was examined in a sub-sample of 6 schools and 35 classes comprising 659 students. The self-assessment multiple-item scales showed longitudinal and multiple group invariance. Factor scores were extracted to compute difference scores for effectiveness (Posttest minus Pretest) and sustainability (Follow-up test minus Posttest) for cyberbullying and cyber victimization. Multilevel Modeling was applied to examine (i) the effectiveness and (ii) the sustainability of the ViSC intervention controlling for several individual and class level variables. Controlling for covariates, it was demonstrated that the ViSC program is effective in preventing cyberbullying and cyber-victimization and that the effects are sustainable after 6 months. The consequences for cyberbullying prevention are discussed. PMID- 26879897 TI - Evidence-based intervention against bullying and cyberbullying: Evaluation of the NoTrap! program in two independent trials. AB - The NoTrap! (Noncadiamointrappola!) program is a school-based intervention, which utilizes a peer-led approach to prevent and combat both traditional bullying and cyberbullying. The aim of the present study was to evaluate the efficacy of the third Edition of the program in accordance with the recent criteria for evidence based interventions. Towards this aim, two quasi-experimental trials involving adolescents (age M = 14.91, SD = .98) attending their first year at different high schools were conducted. In Trial 1 (control group, n = 171; experimental group, n = 451), latent growth curve models for data from pre-, middle- and post tests showed that intervention significantly predicted change over time in all the target variables (victimization, bullying, cybervictimization, and cyberbullying). Specifically, target variables were stable for the control group but decreased significantly over time for the experimental group. Long-term effects at the follow up 6 months later were also found. In Trial 2 (control group, n = 227; experimental group, n = 234), the moderating effect of gender was examined and there was a reported decrease in bullying and cyberbullying over time (pre- and post-test) in the experimental group but not the control group, and this decrease was similar for boys and girls. PMID- 26879898 TI - How accessible are coral reefs to people? A global assessment based on travel time. AB - The depletion of natural resources has become a major issue in many parts of the world, with the most accessible resources being most at risk. In the terrestrial realm, resource depletion has classically been related to accessibility through road networks. In contrast, in the marine realm, the impact on living resources is often framed into the Malthusian theory of human density around ecosystems. Here, we develop a new framework to estimate the accessibility of global coral reefs using potential travel time from the nearest human settlement or market. We show that 58% of coral reefs are located < 30 min from the nearest human settlement. We use a case study from New Caledonia to demonstrate that travel time from the market is a strong predictor of fish biomass on coral reefs. We also highlight a relative deficit of protection on coral reef areas near people, with disproportional protection on reefs far from people. This suggests that conservation efforts are targeting low-conflict reefs or places that may already be receiving de facto protection due to their isolation. Our global assessment of accessibility in the marine realm is a critical step to better understand the interplay between humans and resources. PMID- 26879899 TI - Assessment of glycemic control using glycated hemoglobin among diabetic patients in Jimma University specialized hospital, Ethiopia. AB - BACKGROUND: Globally, diabetes mellitus (DM) has risen dramatically over the past two decades and is expected to keep rising for the next 20 years. If uncontrolled it may lead to complications to the patients that could be prevented or delayed. The disease could be diagnosed and monitored by blood glucose and/or glycated hemoglobin (HbA1) testing. HbA1 can tell long term hyperglycemia of the last 2-3 months period and can predict the risk of diabetic complications; however, the use of glycated hemoglobin test in the country, specifically, in the study area is almost none. Therefore, this study had the aim of assessing glycemic control and describing the risk of complications among diabetic patients using glycated hemoglobin. METHODS: Cross-sectional study was conducted in Jimma University specialized hospital among 148 diabetic patients from May to July 2012. After the study was ethically approved, HbA1, random blood sugar (RBS), socio-demographic data and clinical information were collected from every diabetic patients who were willing to participate in the study among patients coming to the hospital for their routine follow up visits. RESULTS: Even though all the study participants were on diabetes treatment, majority of them were found to be poor glycemic control. It was found out that the mean HbA1 and RBS level of the participants were 7.6 % and 280 mg/dL (15.5 mmol/L), respectively. Using HbA1,5 9.5 % of the patients had poor glycemic control and these patients were considered to be at higher risk of developing complications. Among all the study subjects with poor glycemic control, 70.8 % were within 15-30 years of age; 62.3 % were females; 60.8 % were urban dwellers; 67.4 % were illiterate; 69.6 % were with BMI less than 18.5 kg/m(2), and 61.4 % were taking injectable drugs. Among 136 patients whose clinical history was reviewed, 52.9 % had one or more documented history of major microvascular complications: visual disturbance accounting for 21.3 %, nephropathy 19.1 % and peripheral neuropathy 13.2 %. Eighty-four had poor glycemic control of which 54.7 % had already documented history of one or more complications but the remaining 45.2 % had no documented history. CONCLUSION: Even if all of the diabetic patients were on treatment, the mean HbA1 level as well as RBS level of the study subjects was above the normal range indicating poor glycemic control. More than half of diabetic patients in the hospital had poor glycemic control and were at higher risk of developing diabetic complications or they already developed the complications. Accordingly we recommended tracing the cause of this poor glycemic control for mitigating the problem. PMID- 26879900 TI - delta-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium. AB - Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia induced myocardial infarction and lethal ventricular arrhythmias. delta-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5-8 daily, 5-10 min cycles of moderate, normobaric hypoxia (FIO2 0.095-0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 MUg/kg, sc) or antioxidant N acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 +/- 5 % (n = 12) to 1.8 +/- 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 +/- 0.3 to 0.7 +/- 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 +/- 5 % and arrhythmia score 3.7 +/- 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 +/- 3 % and arrhythmia score 4.7 +/- 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 +/- 8 %; arrhythmia score 4.5 +/- 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia. PMID- 26879901 TI - Spectroscopic Study of Terahertz Generation in Mid-Infrared Quantum Cascade Lasers. AB - Terahertz quantum cascade laser sources based on intra-cavity difference frequency generation are currently the only room-temperature mass-producible diode-laser-like emitters of coherent 1-6 THz radiation. Device performance has improved dramatically over the past few years to reach milliwatt-level power output and broad tuning from 1.2 to 5.9 THz, all at room-temperature. Terahertz output in these sources originates from intersubband optical nonlinearity in the laser active region. Here we report the first comprehensive spectroscopic study of the optical nonlinearity and investigate its dependence on the mid-infrared pump frequencies. Our work shows that the terahertz generation efficiency can vary by a factor of 2 or greater depending on the spectral position of the mid infrared pumps for a fixed THz difference-frequency. We have also measured for the first time the linewidth for transitions between the lower quantum cascade laser states, which is critical for determining terahertz nonlinearity and predicting optical loss in quantum cascade laser waveguides. PMID- 26879902 TI - Low serum albumin and advanced age predict early mortality in Asian patients with extreme elevations of serum aminotransferase. AB - OBJECTIVE: Extreme elevations of serum aminotransferases (EESAT), defined as alanine transaminase (ALT) or aspartate transaminase (AST) level of above 3000 U/L, reflect severe liver injury and poor outcomes of the patients. This study aimed to evaluate the prevalence, etiology and clinical outcomes of EESAT in Asian patients and to identify the predictors of early mortality. METHODS: Medical records of patients with EESAT over a 1-year period were retrospectively analyzed for disease prevalence, etiology and clinical outcome. The primary outcome was 28-day mortality (defined as death occurring within 28 days of the onset of EESAT). A logistic regression was performed to identify independent predictors of mortality. RESULTS: A total of 101 patients with a mean age of 57.4 +/- 18.0 years met the criteria for EESAT, resulted in a prevalence of 1.4 per 1000 admissions. Altogether 63.4% of the patients were men. The etiologies of EESAT were hypoxic hepatitis (74.2%), viral hepatitis (20.8%), rhabdomyolysis (3.0%), drug-induced hepatitis (1.0%) and choledocholithiasis (1%). The 28-day mortality of EESAT was 53.5%. EESAT due to hypoxic hepatitis was associated with high mortality (70.7%) whereas the mortality risk was low in EESAT from viral hepatitis (9.5%). Serum albumin <28 g/L (HR 5.78, 95% CI 1.41-23.62) and age >55 years (HR 4.81, 95% CI 1.29-17.90) were independent predictors of mortality. CONCLUSIONS: The main etiology of EESAT is hypoxic hepatitis, which carries a high mortality. EESAT due to viral hepatitis is common in Asians and has a good outcome. Low serum albumin and elder age are independent predictors of early mortality in EESAT patients. PMID- 26879903 TI - Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells. AB - BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis and a valuable prognostic marker of a diverse array of cancers, including liver cancer; however, the relationship between AEG-1 and hepatic fibrogenesis is not known. OBJECTIVE: The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs). METHODS: The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-beta (TGF-beta)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro. RESULTS: AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-beta or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and alpha-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway. CONCLUSIONS: Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis. PMID- 26879904 TI - Immune/Inflammatory Response and Hypocontractility of Rabbit Colonic Smooth Muscle After TNBS-Induced Colitis. AB - BACKGROUND: The contractility of colonic smooth muscle is dysregulated due to immune/inflammatory responses in inflammatory bowel diseases. Inflammation in vitro induces up-regulation of regulator of G-protein signaling 4 (RGS4) expression in colonic smooth muscle cells. AIMS: To characterize the immune/inflammatory responses and RGS4 expression pattern in colonic smooth muscle after induction of colitis. METHODS: Colitis was induced in rabbits by intrarectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Innate/adaptive immune response RT-qPCR array was performed using colonic circular muscle strips. At 1-9 weeks after colonic intramuscular microinjection of lentivirus, the distal and proximal colons were collected, and muscle strips and dispersed muscle cells were prepared from circular muscle layer. Expression levels of RGS4 and NFkappaB signaling components were determined by Western blot analysis. The biological consequences of RGS4 knockdown were assessed by measurement of muscle contraction and phospholipase C (PLC)-beta activity in response to acetylcholine (ACh). RESULTS: Contraction in response to ACh was significantly inhibited in the inflamed colonic circular smooth muscle cells. RGS4, IL-1, IL-6, IL-8, CCL3, CD1D, and ITGB2 were significantly up-regulated, while IL-18, CXCR4, CD86, and C3 were significantly down-regulated in the inflamed muscle strips. RGS4 protein expression in the inflamed smooth muscles was dramatically increased. RGS4 stable knockdown in vivo augmented ACh stimulated PLC-beta activity and contraction in colonic smooth muscle cells. CONCLUSION: Inflamed smooth muscle exhibits up-regulation of IL-1-related signaling components, Th1 cytokines and RGS4, and inhibition of contraction. Stable knockdown of endogenous RGS4 in colonic smooth muscle increases PLC-beta activity and contractile responses. PMID- 26879905 TI - Synergistic anti-malarial action of cryptolepine and artemisinins. AB - BACKGROUND: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. METHODS: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. RESULTS: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 +/- 0.02, which was significantly less than the Zadd of 8.3 +/- 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg(-1) po) and in combination with ART (4 mg kg(-1)) showed no significant difference compared to the control group. CONCLUSION: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues. PMID- 26879906 TI - Increased expression of upstream TH2-cytokines in a mouse model of viral-induced asthma exacerbation. AB - BACKGROUND: Exacerbations of asthma caused by respiratory viral infections are serious conditions in need of novel treatment. To this end animal models of asthma exacerbations are warranted. We have shown that dsRNA challenges or rhinoviral infection produce exacerbation effects in mice with ovalbumin (OVA) induced allergic asthma. However, house dust mite (HDM) is a more human asthma relevant allergen than OVA. We thus hypothesised that dsRNA challenges in mice with HDM-induced experimental asthma would produce important translational features of asthma exacerbations. METHOD: Mouse airways were challenged locally with HDM or saline three times a week for three weeks to establish experimental asthma. Then daily local dsRNA challenges were given for three consecutive days to induce exacerbation. Bronchoalveolar lavage fluid (BALF) was analysed for inflammatory cells, total protein, the necrosis marker LDH and the alarmin ATP. Lung homogenates were analysed for mRNA expression (RT-qPCR) of TNF-alpha, CCL2, CCL5, IL-1beta, IL-33, thymic stromal lymphopoietin (TSLP), and IL-25 as well as pattern recognition receptors (PRRs) RIG-I, MDA5 and TLR3. Lung tissue IL-33 was analysed with ELISA and PRRs were quantified by western blot. Immunohistochemistry indicated lung distribution of IL-33. RESULTS: HDM challenge alone caused sustained increase in BALF total protein, eosinophils, lymphocytes and neutrophils, and transient increase in lung tissue expression of TSLP, IL-33 and TNF-alpha. dsRNA-induced exacerbation markedly and dose-dependently exaggerated these effects. Further, BALF levels of LDH and ATP, and lung tissue expression of CCL2, CCL5, IL-1beta, IL-25 and PRRs were increased exclusively at the exacerbations. Lung protein levels of IL-33 were transiently increased by HDM and further increased at exacerbation. CONCLUSION: We demonstrate several novel aspects of HDM-induced experimental asthma and added exacerbation effects of dsRNA. General inflammatory parameters in BALF such as exuded proteins, mixed granulocytes, LDH and ATP were increased at the present exacerbations as they are in human asthma exacerbations. We suggest that this model of asthma exacerbation involving dsRNA challenges given to mice with established HDM-induced asthma has translational value and suggest that it may be particularly suited for in vivo studies involving pharmacological effects on exacerbation-induced expression of major upstream TH2-cytokines; IL-33, TSLP and IL-25, as well as PRRs. PMID- 26879908 TI - Forecasting medical waste generation using short and extra short datasets: Case study of Lithuania. AB - The aim of the study is to evaluate the performance of various mathematical modelling methods, while forecasting medical waste generation using Lithuania's annual medical waste data. Only recently has a hazardous waste collection system that includes medical waste been created and therefore the study access to gain large sets of relevant data for its research has been somewhat limited. According to data that was managed to be obtained, it was decided to develop three short and extra short datasets with 20, 10 and 6 observations. Spearman's correlation calculation showed that the influence of independent variables, such as visits at hospitals and other medical institutions, number of children in the region, number of beds in hospital and other medical institutions, average life expectancy and doctor's visits in that region are the most consistent and common in all three datasets. Tests on the performance of artificial neural networks, multiple linear regression, partial least squares, support vector machines and four non-parametric regression methods were conducted on the collected datasets. The best and most promising results were demonstrated by generalised additive (R(2) = 0.90455) in the regional data case, smoothing splines models (R(2) = 0.98584) in the long annual data case and multilayer feedforward artificial neural networks in the short annual data case (R(2) = 0.61103). PMID- 26879909 TI - Anaerobic co-digestion of sewage sludge and food waste. AB - Anaerobic co-digestion of organic matter improves digester operating characteristics and its performance. In the present work, food waste was collected from the institute cafeteria. Two types of sludge (before centrifuge and after centrifuge) were collected from the fluidised bed reactor of the institute treating sewage wastewater. Food waste and sludge were studied for their physico-chemical characteristics, such as pH, chemical oxygen demand, total solids, volatile solids, ammoniacal nitrogen, and total nitrogen. A biomethane potential assay was carried out to find out the optimum mixing ratio of food waste and sludge for anaerobic co-digestion. Results indicated that food waste mixed with sludge in the ratio of 1:2 produced the maximum biogas of 823 ml gVS( 1)(21 days) with an average methane content of 60%. Batch studies were conducted in 5 L lab-glass reactors at a mesophilic temperature. The effect of different substrate loading rates on biogas production was investigated. The mixing ratio of food waste and sludge was 1:2. A loading rate of 1 gVS L d(-1)gave the maximum biogas production of 742 ml g(-1)VS L d(-1)with a methane content of 50%, followed by 2 gVS L d(-1)with biogas of 539 ml g(-1)VS L d(-1) Microbial diversity of the reactor during fed batch studies was investigated by terminal restriction fragment length polymorphism. A pilot-scale co-digestion of food waste and sludge (before centrifuge) indicated the process stability of anaerobic digestion. PMID- 26879910 TI - Injectable pullulan hydrogel for the prevention of postoperative tissue adhesion. AB - Methods for reducing and preventing postoperative abdominal adhesions have been researched for decades; however, despite these efforts, the formation of postoperative peritoneal adhesions is continuously reported. Adhesions cause serious complications such as postoperative pain, intestinal obstruction, and infertility. Tissue adhesion barriers have been developed as films, membranes, knits, sprays, and hydrogels. Hydrogels have several advantages when used as adhesion barriers, including flexibility, low tissue adhesiveness, biodegradability, and non-toxic degraded products. Furthermore, compared with preformed hydrogels, injectable hydrogels can fill and cover spaces of any shape and do not require a surgical procedure for implantation. In this study, pullulan was modified through reaction with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) to introduce carboxyl and phenyl groups as crosslinking sites. The grafting of tyramine on pullulan allows crosslinking branches on pullulan backbone. We successfully fabricated pullulan hydrogel with an enzymatic reaction using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The chemical structure of modified pullulan was analyzed with ATR-FTIR and (1)H NMR spectroscopies. Rheological properties were tested by measuring storage modulus with varying H2O2, HRP, polymer solution concentrations and tyramine substitution rates. Cell viability and animal tests were performed. The modified pullulan hydrogel is an invaluable advance in anti adhesion agents. PMID- 26879911 TI - Composition and anti-inflammatory effect of polysaccharides from Sargassum horneri in RAW264.7 macrophages. AB - Sulfated polysaccharides extracted from brown marine algae have been shown to possess a variety of biological activities. We assessed the potential activity of the sulfated polysaccharide from Sargassum horneri (SP) and its isolated two major components (fraction-1 (F1) and fraction-2 (F2)), on anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In the present study, analysis of polysaccharide chemical composition found that the constituent ratios of sulfate ester and fucose in SP and F1 were 4.95% vs 7.6%, and 4.48% vs 55.9%, respectively, suggesting that F1 may be a major sulfated polysaccharide containing fucose. Meanwhile, our findings demonstrated that TNF alpha secretion levels were significantly (P<0.05) decreased by SP and F1 treatments in LPS-stimulated RAW264.7 cells in a dose-dependent manner under the preventive and repair experimental models. Pro-/anti-inflammatory (TNF-alpha/IL 10) cytokines secretion ratios by LPS-stimulated RAW264.7 macrophages were significantly (P<0.05) inhibited by SP and F1 treatments, particularly by F1 (at high dose, 200MUg/ml). Moreover, NO release and iNOS activity were significantly (P<0.05) inhibited by F1. Collectively, the present study suggested that purified component, F1 from SP, had strong anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages in the preventive and repair manner through inhibiting TNF alpha secretion levels and NO release. PMID- 26879912 TI - Removal of Pb(II) and Cd(II) ions from aqueous solution by thiosemicarbazide modified chitosan. AB - The removal of Pb(II) and Cd(II) ions from aqueous solution by thiosemicarbazide modified chitosan (TCS) was studied in this article. The synthesized TCS was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), element analysis, N2 adsorption-desorption, scanning electron microscopy (SEM) and X-ray photoelectron spectrophotometer (XPS). Moreover, the influence of solution pH, contact time, initial heavy metal concentration, and solution temperature on the adsorption process was examined, and the adsorbent reusability and adsorption mechanisms were also studied. The results showed that TCS adsorbed greater amount of Pb(II) and Cd(II) ions than the raw chitosan. The adsorption amounts of Pb(II) and Cd(II) ions were affected by increasing solution pH and temperature. The maximum adsorption capacities of the TCS for Pb(II) and Cd(II) ions were found to be 325.2 and 257.2 mg/g, respectively. The endothermic adsorption fitted the pseudo-second-order kinetics equation and the adsorption isotherms could be well described by Langmuir model. The metal ions adsorption mechanism was concluded to be mainly dominated by complexation reaction process. The desorption study indicated that the target adsorbent was easy to be regenerated. PMID- 26879907 TI - Adult neurogenesis and neurodegenerative diseases: A systems biology perspective. AB - New neurons are generated throughout adulthood in two regions of the brain, the olfactory bulb and dentate gyrus of the hippocampus, and are incorporated into the hippocampal network circuitry; disruption of this process has been postulated to contribute to neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. Known modulators of adult neurogenesis include signal transduction pathways, the vascular and immune systems, metabolic factors, and epigenetic regulation. Multiple intrinsic and extrinsic factors such as neurotrophic factors, transcription factors, and cell cycle regulators control neural stem cell proliferation, maintenance in the adult neurogenic niche, and differentiation into mature neurons; these factors act in networks of signaling molecules that influence each other during construction and maintenance of neural circuits, and in turn contribute to learning and memory. The immune system and vascular system are necessary for neuronal formation and neural stem cell fate determination. Inflammatory cytokines regulate adult neurogenesis in response to immune system activation, whereas the vasculature regulates the neural stem cell niche. Vasculature, immune/support cell populations (microglia/astrocytes), adhesion molecules, growth factors, and the extracellular matrix also provide a homing environment for neural stem cells. Epigenetic changes during hippocampal neurogenesis also impact memory and learning. Some genetic variations in neurogenesis related genes may play important roles in the alteration of neural stem cells differentiation into new born neurons during adult neurogenesis, with important therapeutic implications. In this review, we discuss mechanisms of and interactions between these modulators of adult neurogenesis, as well as implications for neurodegenerative disease and current therapeutic research. (c) 2016 Wiley Periodicals, Inc. PMID- 26879913 TI - The efficacy of a sulphated polysaccharide fraction from Hypnea musciformis against diarrhea in rodents. AB - Seaweeds are sources of diverse bioactive compounds, such as sulphated polysaccharides. This study was designed to evaluate the chemical composition and anti-diarrheal activity of a fraction of sulphated polysaccharide (PLS) obtained from the red seaweed Hypnea musciformis in different animal models, and to elucidate the underlying mechanisms. PLS was obtained by aqueous extraction, with a yield of 31.8% of the seaweed dry weight. The total carbohydrate content accounted for 99% of the sample. The sulfate content of the polysaccharide was 5.08% and the percentage of carbon was 25.98%. Pretreatment with all doses of PLS inhibited castor oil-induced diarrhea, with reduction of the total amount of stool, diarrheal stools, and the severity of diarrhea. PLS (90 mg/Kg) decreased castor oil- and PGE2-induced enteropooling. In addition, PLS (90 mg/Kg) increased the Na(+)/K(+)-ATPase activity in the small intestine and reduced gastrointestinal transit, possibly via activation of cholinergic receptors. Interestingly, the cholera toxin-induced fluid secretion and Cl(-) ion levels decreased in the intestinal contents of the animals pretreated with PLS (90 mg/kg), probably via reduction of toxin-GM1 receptor binding. In conclusion, PLS exerts anti-diarrheal activity by increasing Na(+)/K(+)-ATPase activity, inhibiting gastrointestinal motility, and blocking the toxin-GM1 receptor binding. PMID- 26879915 TI - Negative consequences of other people's drinking: Prevalence, perpetrators and locations. AB - INTRODUCTION AND AIMS: While both policy makers and researchers have shown renewed interest in drinking and harm to others, several questions concerning the issue remain unanswered. The aim of this study was to address some of these questions by: (i) presenting updated figures on the prevalence of experienced harm from other people's drinking in various sub-groups; and (ii) examining in which locations such episodes most often occur and who the perpetrators usually are. DESIGN AND METHODS: Data were obtained from a general population survey among 16- to 79-year-old Norwegians (n = 1947), where experiences of five negative consequences related to other people's drinking (e.g. physical abuse and verbal abuse) were assessed. Those who reported such experiences were asked to specify at which location the last episode occurred and who the perpetrator was. RESULTS: Altogether, 17.3% had experienced one or more problems during the past 12 months. Persons who were young, not living with a partner, an urban resident, with low education and often intoxicated were at increased risk. The direction of statistically significant gender differences depended on the type of problem. While the episodes were spread across different locations (private homes, on premise outlets and outdoors), perpetrators were more often strangers or friends/acquaintances than partners or family members. DISCUSSION AND CONCLUSIONS: In a preventive perspective, increased knowledge regarding the context of episodes where people experience harm from other people's drinking is important. We have shed some light on this issue by examining the locations and perpetrators of such episodes. [Storvoll EE, Moan IS, Lund IO. Negative consequences of other people's drinking: Prevalence, perpetrators and locations. Drug Alcohol Rev 2016;35:755-762]. PMID- 26879914 TI - Morphologic and neuropsychological patterns in patients suffering from Alzheimer's disease. AB - INTRODUCTION: We conducted a retrospective study to identify morphological subgroups of patients referred for AD or aMCI and to seek for differences across neuropsychological performances. METHODS: One hundred forty-five patients (mean age = 76.01, 88 women and 57 men) referred for AD, either at the stage of dementia or aMCI, were examined using structural MRI. Five observers reviewed blindly twice all examinations. We rated microangiopathy, hippocampal, parietal atrophies, including a gradient of fronto-parietal atrophy (GFPA). A multiple component analysis (MCA) followed by a hierarchical ascending classification was conducted to identify morphologically distinct subgroups. Among these, 76 patients completed all the neuropsychological tests. Univariate and multivariate analyses were further conducted on these data across morphological subgroups. The institutional review board approved the research protocol. RESULTS: Inter- and intra-raters' agreements were excellent and very good for microangiopathy and hippocampal atrophy ratings. They were higher for GFPA than for the parietal atrophy scale. MCA without priors identified three groups: group 1 was characterized by no/discrete microangiopathy, severe hippocampal, and predominant parietal atrophy; group 2 had significant microangiopathy, severe hippocampal atrophy, and no predominant parietal atrophy; group 3 had a mild hippocampal atrophy and parietal atrophies. In group 1, working memory profile was less impaired than in group 2 (p = 0.01). Neuropsychological performances of group 3 were higher in most domains. CONCLUSION: Combined characterization of microangiopathy, hippocampal, parietal, and GFPA allows identifying morphological subgroups among patients referred for AD and at risk. These groups have some neuropsychological differences, suggesting different pathophysiological mechanisms or co-existing conditions. PMID- 26879916 TI - Enhancing the energy density of safer Li-ion batteries by combining high-voltage lithium cobalt fluorophosphate cathodes and nanostructured titania anodes. AB - Recently, Li-ion batteries have been heavily scrutinized because of the apparent incompatibility between safety and high energy density. This work report a high voltage full battery made with TiO2/Li3PO4/Li2CoPO4F. The Li2CoPO4F cathode and TiO2 anode materials are synthesized by a sol-gel and anodization methods, respectively. X-ray diffraction (XRD) analysis confirmed that Li2CoPO4F is well crystallized in orthorhombic crystal structure with Pnma space group. The Li3PO4 coated anode was successfully deposited as shown by the (011) lattice fringes of anatase TiO2 and (200) of gamma-Li3PO4, as detected by HRTEM. The charge profile of Li2CoPO4F versus lithium shows a plateau at 5.0 V, revealing its importance as potentially high-voltage cathode and could perfectly fit with the plateau of anatase anode (1.8-1.9 V). The full cell made with TiO2/Li3PO4/Li2CoPO4F delivered an initial reversible capacity of 150 mA h g(-1) at C rate with good cyclic performance at an average potential of 3.1-3.2 V. Thus, the full cell provides an energy density of 472 W h kg(-1). This full battery behaves better than TiO2/Li2CoPO4F. The introduction of Li3PO4 as buffer layer is expected to help the cyclability of the electrodes as it allows a rapid Li-ion transport. PMID- 26879918 TI - The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment. AB - PURPOSE: Grading inter-vertebral disc degeneration (IDD) is important in the evaluation of many degenerative conditions, including patients with low back pain. Magnetic resonance imaging (MRI) is considered the best imaging instrument to evaluate IDD. The Pfirrmann classification is commonly used to grade IDD; the authors describing this classification showed an adequate agreement using it; however, there has been a paucity of independent agreement studies using this grading system. The aim of this study was to perform an independent inter- and intra-observer agreement study using the Pfirrmann classification. METHODS: T2 weighted sagittal images of 79 patients consecutively studied with lumbar spine MRI were classified using the Pfirrmann grading system by six evaluators (three spine surgeons and three radiologists). After a 6-week interval, the 79 cases were presented to the same evaluators in a random sequence for repeat evaluation. The intra-class correlation coefficient (ICC) and the weighted kappa (wkappa) were used to determine the inter- and intra-observer agreement. RESULTS: The inter-observer agreement was excellent, with an ICC = 0.94 (0.93-0.95) and wkappa = 0.83 (0.74-0.91). There were no differences between spine surgeons and radiologists. Likewise, there were no differences in agreement evaluating the different lumbar discs. Most differences among observers were only of one grade. Intra-observer agreement was also excellent with ICC = 0.86 (0.83-0.89) and wkappa = 0.89 (0.85-0.93). CONCLUSIONS: In this independent study, the Pfirrmann classification demonstrated an adequate agreement among different observers and by the same observer on separate occasions. Furthermore, it allows communication between radiologists and spine surgeons. PMID- 26879919 TI - Surgical management of an osteoblastoma involving the entire C2 vertebra and a review of literature. AB - PURPOSE: The purpose of this study was to evaluate the surgical management of an osteoblastoma involving the entire C2 vertebra. MATERIALS AND METHODS: A 14-year old girl presented with unbearable neck pain. Her medical history was unremarkable. Computed tomography and magnetic resonance imaging revealed lytic and osteoblastic bone lesions involving the entire C2 vertebra. The tumor was resected in two stages with vertebral artery mobilization. Histological examination confirmed the diagnosis of osteoblastoma. The pain resolved postoperatively, and the patient had no further complaints. Sufficient fusion formation and no tumor recurrence with no complaints were seen in postoperatively 4 years. CONCLUSION: Marginal resection remains the best treatment for osteoblastoma of the spine. If tumor tissue surrounds the vertebral artery, the vertebral artery should be mobilized and the surrounding tumor mass excised. PMID- 26879920 TI - A pilot orthopedic trauma registry in Ugandan district hospitals. AB - BACKGROUND: Musculoskeletal injuries are a major public health problem in low income countries like Uganda. Patterns of musculoskeletal injuries presenting to district hospitals are unknown. Our pilot orthopedic trauma registry establishes a framework for broader district hospital injury surveillance. MATERIALS AND METHODS: We interviewed and examined patients presenting to Mityana, Entebbe, and Nakaseke hospitals with musculoskeletal injuries from October 2013 to January 2014. We compared patient and Demographic and Health Survey population demographics and determined predictors of delayed presentation for care. RESULTS: Men, adults, and individuals with postsecondary education were more common among patients than in the Demographic and Health Survey population. Common causes included road traffic injuries (48.5%) and falls (25.1%). Closed, simple fractures comprised 70% of injuries. Compared to the self-employed, subsistence farmers (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.15-7.91), motorcycle taxi drivers (OR = 10.50, 95% CI = 1.92-64.57), and preschool children (OR = 4.24, 95% CI = 1.05-17.39) were significantly more likely to be delayed to care after adjustment for covariates. Subsistence farmers were more likely than other occupations to seek care from traditional bonesetters (23% versus 7%, P = 0.001). All patients who visited bonesetters were delayed to hospital care. CONCLUSIONS: Policies for trauma systems strengthening must address the needs of underserved groups and involve all stakeholders, including bonesetters. Research should address reasons for delayed care among subsistence farmers, motorcycle taxi drivers, and preschool children. Injury surveillance at district hospitals facilitates evidence-based resource allocation and should continue in the form of an Ugandan national trauma registry. PMID- 26879921 TI - Long-term outcomes for children with acute lymphoblastic leukemia (ALL) treated on The Cancer Institute of New Jersey ALL trial (CINJALL). AB - The Cancer Institute of New Jersey Acute Lymphoblastic Leukemia trial (CINJALL) employed a post-induction regimen centered on intensive oral antimetabolite therapy, with no intravenous methotrexate (MTX). Fifty-eight patients enrolled between 2001 and 2005. A high rate of induction death (n = 3) or induction failure (n = 1) was observed. Among those who entered remission, five-year DFS is 80 +/- 8.9% for those at standard risk of relapse and 76 +/- 7.8% for high-risk patients, with median follow up over six years. The estimated cumulative incidence of testicular relapse among boys was elevated (13 +/- 7.2%) compared to the rate observed on contemporary protocols. We conclude that post-induction therapy using intensive oral antimetabolites for children with acute lymphoblastic leukemia (ALL) can result in overall long-term DFS comparable to that observed among children treated with regimens including intravenous MTX. However, an increased risk of late extramedullary relapse among boys was observed, supporting the prevailing opinion that high-dose MTX improves outcome for children with ALL. PMID- 26879923 TI - Assessment of surgery for the underdeveloped thumb. PMID- 26879922 TI - The Integration of Noninvasive Prenatal Screening into the Existing Prenatal Paradigm: a Survey of Current Genetic Counseling Practice. AB - Since its introduction four years ago, noninvasive prenatal screening for fetal aneuploidy (NIPS) has been widely adopted as a screening tool for women at a high risk for fetal aneuploidy. As use expands into the general population, questions arise concerning the integration of NIPS into preexisting screening paradigms. This study aims to examine the use of NIPS in current practice among prenatal counselors, predominantly in the United States, in order to inform strategies for the optimal use of both new and existing screening techniques. We electronically surveyed 208 members of the National Society of Genetic Counselors to ascertain how NIPS is currently being used. Genetic counselors were also queried as to the advantages and disadvantages of offering NIPS to all patients regardless of a priori risk. Results indicate substantial variation in practice regarding which patients are offered NIPS and how counselors have incorporated this technology into existing screening routines. The majority of participants report offering NIPS in conjunction with another method of screening for fetal aneuploidy, indicating that NIPS is being used as an addition rather than as a replacement. These screening methods primarily include nuchal translucency (NT) (45.1 %, n = 78) and first trimester serum screening, with or without an NT (19.7 %, n = 34). Furthermore, the majority report that they would be concerned about losing the clinical value of an NT in a complete transition to NIPS (85.4 %, n = 164). Counselors are evenly split on the merits of expanding the use of NIPS to the general population (con: 55.3 %, n = 105; pro: 44.7 %, n = 85). The lack of consensus suggests that updated practice guidelines might benefit counselors. In addition, respondents emphasized the need to better educate patients and providers about the risks, benefits, and limitations of the test. PMID- 26879924 TI - Zhao L, Chen X, Zhang L. Digital necrosis after triamcinolone acetonide injection for trigger thumb: case report. J Hand Surg Eur. 2015, 40:741-2. PMID- 26879926 TI - Atorvastatin (Lipitor) attenuates the effects of aspirin on pancreatic cancerogenesis and the chemotherapeutic efficacy of gemcitabine on pancreatic cancer by promoting M2 polarized tumor associated macrophages. AB - BACKGROUND: Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated. We scanned the dynamic changes of pan-inflammatory cell populations in pancreatic cancerogensis and after chemotherapy and found the potential target cell populations. Then we tested the roles of aspirin and Lipitor to regulate these inflammatory cell populations and their effects on pancreatic cancerogenesis and chemotherapeutic effects. METHODS: Cancerogen, dimethylbenzanthracene (DMBA), was used to induce pancreatic cancerogenesis and subcatunous implantation of syngenic murine Panc02 pancreatic cancer cells was adopted as well. Gemcitabine was used for chemotherapy. The peripheral blood, pancreatic lesions and tumor samples were harvested and analyzed to search for the potential target cell populations. The roles of aspirin and Lipitor to regulate these cell populations and their potential effects on pancreatic cancerogenesis and chemotherapeutic efficacy were investigated both in vitro and in vivo. RESULTS: We found progressive accumulations of myeloid-derived suppressor cells (MDSC) and M2-polarzied tumor associated macrophages(M2) in pancreatic lesions accompanied with dynamic reducations of cytotoxic T cells(CTL) and helper T cells(Th) in the progression of pancreatic cancerogenesis. After gemcitabine treatment, the MDSC significantly reduced, however M2 soared up unexpectedly. Aspirin could significantly inhibit the MDSC and M2 to prevent pancreatic cancerogenesis and improve chemotherapeutic effects of gemcitabine, however Lipitor did not significantly affect MDSC, instead it could promote M2 to attenuate the postive effects of aspirin and gemcitabine. CONCLUSIONS: MDSC and M2 accumulate in progression of pancreatic cancerogenesis and gemcitabine can induce M2. Aspirin could prevent pancreatic cancerogenesis and improve efficacy of gemcitabine partially by inhibiting MDSC and M2, however when used in combination, Lipitor could weaken the efficacy of aspirin and gemcitabine partially by promoting M2. PMID- 26879927 TI - Validation of the Sour Seven Questionnaire for screening delirium in hospitalized seniors by informal caregivers and untrained nurses. AB - BACKGROUND: Delirium is a common condition in hospitalized seniors that nonetheless often goes undetected by nurses or is delayed in being detected which negatively impacts quality of care and outcomes. We sought to develop a new screening tool for delirium, The Sour Seven Questionnaire, a 7-item questionnaire suitable to be completed from informal or untrained caregiver observation. The study aimed to develop the scoring criteria for a positive delirium screen and assess concurrent validity of the questionnaire against a geriatric psychiatrist's assessment. METHODS: A pilot study of 80 hospitalized seniors over age 65 recruited from three units (2 medical, 1 orthopedic). Participants were assessed using the Confusion Assessment Method (CAM) with a brief cognitive screen and the Sour Seven Questionnaire posed to the appointed informal caregiver (family member) or untrained nurse for up-to 7 days. Subjects testing positive on the CAM and a random sample of negatively CAM screened subjects were assessed by the geriatric psychiatrist. RESULTS: From 80 participants, 21 screened positive for delirium on the CAM. 18 of the 21 CAM positive screens were diagnosed to have delirium by the geriatric psychiatrist, and 17 of the 18 randomly assigned negative CAM screens were confirmed as not having delirium. From the questionnaires on these 39 participants, weighted scoring for each of the 7 questions of the Sour Seven Questionnaire was developed based on their relative risks for correctly predicting delirium when compared to the geriatric psychiatrist's clinical assessment. Total scoring of the questionnaire resulted in the following positive predictive values for delirium: 89% with a total score of 4 (sensitivity 89.5%, specificity 90%), and 100% with a total score of 9 (sensitivity 63.2%, specificity 100%). Comparison between scoring on questionnaires posed to informal caregivers versus untrained nurses showed no differences. CONCLUSION: A weighted score of 4 in the Sour Seven Questionnaire has concurrent validity as a screening tool for delirium and a score of 9 is diagnostic for delirium. The Sour Seven Questionnaire is the first screening tool for delirium shown to be suitable for use by informal caregivers and untrained nurses in hospitalized seniors. PMID- 26879928 TI - Normocellular CSF in herpes simplex encephalitis. AB - BACKGROUND: Herpes simplex virus (HSV) is the most common cause of sporadic encephalitis worldwide. The high mortality rate (70-80 %) of herpes simplex encephalitis (HSE) can be reduced to 20-30 % by antiviral therapy. However, normocellular CSF can lure physicians to look for non-infectious causes, resulting in delayed treatment. This study aimed to investigate, characterize and differentiate HSE patients, with normocellular and pleocytosis CSF, according to neuroimaging patterns, underlying disease, CSF viral load and clinical outcome. Patients with proven (by PCR positive CSF) or presumed viral infections of the CNS admitted to King Chulalongkorn Memorial Hospital between January 2002 and 2011 were analyzed. RESULTS: HSV was detected in the CSF of 43 patients but only 23 patients had encephalitis. Among these 23 patients, 6 cases (26.1 %) had normal CSF WBC (<5 cells/mm(3)). One patient in this normocellular CSF group had HIV infection. Although this patient had low CD4 counts (<200 cells/mm(3)), the peripheral WBC counts showed only mild leukopenia. The CSF HSV viral load in the pleocytosis group was higher than the normocellular group, with an average of 12,200 vs 3027 copies/ml respectively. There was no correlation between the viral load and the clinical outcome. With respect to neuroimaging, 4 (66.7 %) patients in the normocellular group had unremarkable/non-specific results. CONCLUSIONS: Normocellular CSF in HSE is not rare, and can be seen in normal as well as immunocompromised hosts. Clinicians should not exclude CNS infection, especially HSE, merely based on the absence of CSF pleocytosis and/or unremarkable neuroimaging study. PMID- 26879925 TI - Depression During Pregnancy and Postpartum. AB - Depression is a common complication of pregnancy and the postpartum period. There are multiple risk factors for peripartum mood disorders, most important of which is a prior history of depression. Both depression and antidepressant medications confer risk upon the infant. Maternal depression has been associated with preterm birth, low birth weight, fetal growth restriction, and postnatal cognitive and emotional complications. Antidepressant exposure has been associated with preterm birth, reductions in birth weight, persistent pulmonary hypertension, and postnatal adaptation syndrome (PNAS) as well as a possible connection with autism spectrum disorder. Paroxetine has been associated with cardiac malformations. Most antidepressant medications are excreted in low levels in breast milk and are generally compatible with breastfeeding. The use of antidepressants during pregnancy and postpartum must be weighed against the risk of untreated depression in the mother. PMID- 26879929 TI - Direct Spectroscopic Evidence for an n->pi* Interaction. AB - The n->pi* interaction is an extremely weak but very important noncovalent interaction. Although this interaction is widely present in biomolecules and materials, its existence is counterintuitive and so has been debated extensively. Herein, we have reported direct spectroscopic evidence for an n->pi* interaction for the first time by probing the carbonyl stretching frequency in phenyl formate using isolated gas-phase IR spectroscopy. This result also demonstrates that the conformational preference for the cis conformer of phenyl formate compared to the trans conformer arises due to the presence of the n->pi* interaction in the former. The direct proof reported herein for this controversial but important noncovalent interaction should stimulate further experimental and theoretical investigation on this intriguing research topic. PMID- 26879931 TI - Ecological distribution of leaf stomata and trichomes among tree species in a Malaysian lowland tropical rain forest. AB - The vertical structure of a tropical rain forest is complex and multilayered, with strong variation of micro-environment with height up to the canopy. We investigated the relation between morphological traits of leaf surfaces and tree ecological characteristics in a Malaysian tropical rain forest. The shapes and densities of stomata and trichomes on the abaxial leaf surfaces and their relation with leaf characteristics such as leaf area and leaf mass per area (LMA) were studied in 136 tree species in 35 families with different growth forms in the tropical moist forest. Leaf physiological properties were also measured in 50 canopy and emergent species. Most tree species had flat type (40.4 %) or mound type (39.7 %) stomata. In addition, 84 species (61.76 %) in 22 families had trichomes, including those with glandular (17.65 %) and non-glandular trichomes (44.11 %). Most leaf characteristics significantly varied among the growth form types: species in canopy and emergent layers and canopy gap conditions had higher stomatal density, stomatal pore index (SPI), trichome density and LMA than species in understory and subcanopy layers, though the relation of phylogenetically independent contrasts to each characteristic was not statistically significant, except for leaf stomatal density, SPI and LMA. Intrinsic water use efficiency in canopy and emergent tree species with higher trichome densities was greater than in species with lower trichome densities. These results suggest that tree species in tropical rain forests adapt to a spatial difference in their growth forms, which are considerably affected by phylogenetic context, by having different stomatal and trichome shapes and/or densities. PMID- 26879930 TI - Characterization of triterpenoid profiles and triterpene synthase expression in the leaves of eight Vitis vinifera cultivars grown in the Upper Rhine Valley. AB - Plant triterpenoids are a diverse group of secondary metabolites with wide distribution, high chemical diversity and interesting pharmacological and antimicrobial properties. The first step in the biosynthesis of all triterpenoids is the cyclization of the 2,3-oxidosqualene precursor, catalyzed by oxidosqualene cyclases (OSCs), which have characteristic product specificities. Biosynthesis and functions of pentacyclic triterpenes have been poorly studied in grapevine. In this study, we first investigated the profile of triterpenoids present in leaf cuticular waxes from eight Vitis vinifera cultivars cultivated in the Upper Rhine Valley. Further quantification of triterpenoids showed that these cultivars can be divided into two groups, characterized by high levels of lupeol (e.g., Pinot noir) or taraxerol (e.g., Gewurztraminer) respectively. We further analyzed the OSC family involved in the synthesis of pentacyclic triterpenes (called VvTTPSs) in the sequenced V. vinifera 40024 genome and found nine genes with similarity to previously characterized triterpene synthases. Phylogenetic analysis further showed that VvTTPS1-VvTTPS3 and VvTTPS5-VvTTPS9 belong to the beta-amyrin synthase and multifunctional triterpene synthase clade, whereas VvTTPS10 belongs to the lupeol synthase clade. We studied the expression of several members of the VvTTPS family following biotic and abiotic stresses in V. vinifera 40024 as well as in the eight healthy cultivars. This study further revealed that one candidate gene, VvTTPS5, which does not belong to the lupeol synthase clade, is highly expressed in lupeol-rich cultivars. VvTTPS3, VvTTPS5, VvTTPS6, VvTTPS7 and VvTTPS10 were highly upregulated by UV stress, but only VvTTPS3, VvTTPS5, VvTTPS6 and VvTTPS10 were upregulated following downy mildew and gray mold infections respectively. These results suggest differential roles of VvTTPS against environmental stresses in grape leaves. PMID- 26879932 TI - Genista anglica (Fabaceae): One very diverse species or one species complex? AB - Genista anglica represents a widely distributed group of shrubs in the Iberian Peninsula, as well as in the North of the Moroccan Mountains, the South of Italy and in most oceanic territories of Western Europe, with its northern limit in Sweden. Up to five different species within the group have been described in these territories: Genista ancistrocarpa, G. acutifolia, G. brutia and G. silana, as well as G. anglica sensu stricto. The diversity of Genista anglica sensu lato as well as the phylogenetic patterns that have generated this diversity have been analyzed through the use of nuclear (ITS, ETS) and chloroplastic (trnL, trnL-F, rbcL, matK) DNA sequences. Our results show that the group probably originated in the West of the Iberian Peninsula and subsequently spread to the rest of the European oceanic territories. Additionally, the results support the idea that the presence of a group of plants in the South of Italy, where G. brutia and G. silana were previously described, has been the consequence of the introduction of seeds collected in the Northwest of the Iberian Peninsula. Our results also indicate that, in contrast to some authors, the populations from the West of the Iberian Peninsula are not isolated and, consequently, they should be grouped into one species with high diversity, therefore differentiation into different taxa is no longer adequate. PMID- 26879934 TI - Thanking our peer reviewers. PMID- 26879933 TI - Adaptation and reliability of the Readiness for Inter professional Learning Scale in a Danish student and health professional setting. AB - BACKGROUND: Shared learning activities aim to enhance the collaborative skills of health students and professionals in relation to both colleagues and patients. The Readiness for Interprofessional Learning Scale is used to assess such skills. The aim of this study was to validate a Danish four-subscale version of the RIPLS in a sample of 370 health-care students and 200 health professionals. METHODS: The questionnaire was translated following a two-step process, including forward and backward translations, and a pilot test. A test of internal consistency and a test-retest of reliability were performed using a web-based questionnaire. RESULTS: The questionnaire was completed by 370 health care students and 200 health professionals (test) whereas the retest was completed by 203 health professionals. A full data set of first-time responses was generated from the 570 students and professionals at baseline (test). Good internal association was found between items in Positive Professional Identity (Q13-Q16), with factor loadings between 0.61 and 0.72. The confirmatory factor analyses revealed 11 items with factor loadings above 0.50, 18 below 0.50, and no items below 0.20. Weighted kappa values were between 0.20 and 0.40, 16 items with values between 0.40 and 0.60, and six items between 0.60 and 0.80; all showing p-values below 0.001. CONCLUSION: Strong internal consistency was found for both populations. The Danish RIPLS proved a stable and reliable instrument for the Teamwork and Collaboration, Negative Professional Identity, and Positive Professional Identity subscales, while the Roles and Responsibility subscale showed some limitations. The reason behind these limitations is unclear. PMID- 26879935 TI - Region and dynamic specificities of adult neural stem cells and oligodendrocyte precursors in myelin regeneration in the mouse brain. PMID- 26879938 TI - Prospects of Supercritical Fluids in Realizing Graphene-Based Functional Materials. AB - Supercritical-fluids science and technology predate all the approaches that are currently established for graphene production by several decades in advanced materials design. However, it has only recently been proposed as a plausible approach for graphene processing. Since then, supercritical fluids have emerged into contention as an alternative to existing technologies because of their scalability and versatility in processing graphene materials, which include composites, aerogels, and foams. Here, an overview is presented of such materials prepared through supercritical fluids from an advanced materials science standpoint, with a discussion on their fundamental properties and technological applications. The benefits of supercritical-fluid processing over conventional liquid-phase processing are presented. The benefits include not only better performances for advanced applications but also environmental issues associated with the synthesis process. Nevertheless, the limitations of supercritical-fluid processing are also stressed, along with challenges that are still faced toward the achievement of the great expectations from graphene materials. PMID- 26879936 TI - Novel molecular diagnostic tools for malaria elimination: a review of options from the point of view of high-throughput and applicability in resource limited settings. AB - As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination. To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings. Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/uL making them insufficiently sensitive for detecting all carriers. Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time. This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination. PMID- 26879937 TI - Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders. AB - BACKGROUND: Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. METHODS: A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. RESULTS: Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. CONCLUSIONS: We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder. PMID- 26879939 TI - Sediments and Soils Act as Reservoirs for Taxonomic and Functional Bacterial Diversity in the Upper Mississippi River. AB - In this study, we utilized Illumina next-generation sequencing of 16S rDNA to characterize the bacterial communities in water, sediments, and soils at four sites along the Mississippi River and Minnesota River, in Minnesota, in order to evaluate community exchanges between these habitats. Communities in water and sediment were hypothesized to show greater taxonomic similarity than those in soil, while microbial communities in sediment and soil would show greater functional similarity. Habitat-specific communities showed significant differences in phylogenetic structure and beta-diversity (P < 0.001), but site specific differences in community structures within a single habitat type did not differ greatly (P >= 0.083). Community exchange among habitats generally influenced < 5% of the total community composition in a single sample, with the exception of the sediment community at the Minnesota River site, which contributed to a mean of 14% of the microbial community in the water column. Communities from all habitat types were significantly correlated with each other (r = 0.44-0.64, P <= 0.004). Furthermore, approximately 33% of the taxonomic units were found in all samples and comprised at least 40% of the bacterial community. Functional annotation of shotgun sequencing data revealed similar functional profiles for sediment and soil communities that were distinct from those in the water. Results of this study suggest that sediments, when disturbed, contribute significantly to bacterial communities in the water and that a core bacterial community may be supported in the soils and sediments. Furthermore, a high degree of functional redundancy results in similar functional profiles in sediment and soil communities. PMID- 26879940 TI - The Influence of Time and Plant Species on the Composition of the Decomposing Bacterial Community in a Stream Ecosystem. AB - Foliar chemistry influences leaf decomposition, but little is known about how litter chemistry affects the assemblage of bacterial communities during decomposition. Here we examined relationships between initial litter chemistry and the composition of the bacterial community in a stream ecosystem. We incubated replicated genotypes of Populus fremontii and P. angustifolia leaf litter that differ in percent tannin and lignin, then followed changes in bacterial community composition during 28 days of decomposition using 16S rRNA gene-based pyrosequencing. Using a nested experimental design, the majority of variation in bacterial community composition was explained by time (i.e., harvest day) (R(2) = 0.50). Plant species, nested within harvest date, explained a significant but smaller proportion of the variation (R(2) = 0.03). Significant differences in community composition between leaf species were apparent at day 14, but no significant differences existed among genotypes. Foliar chemistry correlated significantly with community composition at day 14 (r = 0.46) indicating that leaf litter with more similar phytochemistry harbor bacterial communities that are alike. Bacteroidetes and beta-proteobacteria dominated the bacterial assemblage on decomposing leaves, and Verrucomicrobia and alpha- and delta-proteobacteria became more abundant over time. After 14 days, bacterial diversity diverged significantly between leaf litter types with fast-decomposing P. fremontii hosting greater richness than slowly decomposing P. angustifolia; however, differences were no longer present after 28 days in the stream. Leaf litter tannin, lignin, and lignin: N ratios all correlated negatively with diversity. This work shows that the bacterial community on decomposing leaves in streams changes rapidly over time, influenced by leaf species via differences in genotype-level foliar chemistry. PMID- 26879942 TI - [Not Available]. PMID- 26879941 TI - A Pure Life: The Microbial Ecology of High Purity Industrial Waters. AB - The microbial ecology of various natural environments has been an active area of research since the earlier part of the twentieth century. Remote and sometimes extreme environments such as the deep ocean and the deep terrestrial subsurface have revealed a remarkable array of microorganisms. The majority of these environments are nutrient limited, and microorganisms-principally, bacteria-have developed a number of survival strategies that enable their survival and, in some cases, replication. While planktonic microorganisms exist in oligotrophic environments, the predominant mode of survival and growth is associated with biofilms. There are a number of similarities between the physicochemistry of industrial water systems and some natural aquatic ecosystems, and these similarities extend to the microbial populations and the survival mechanisms that are employed. The "starvation-survival" mechanisms, including biofilm formation, may be associated with deleterious effects on industrial water systems. These effects include heat transfer inhibition, microbially influenced corrosion, and contamination of various products manufactured in a wide array of industries. Biological fouling of industrial water systems has significant direct and indirect (through antimicrobial chemical applications) impacts on engineered materials and on the etiology of some waterborne diseases. This review provides an overview of the microbial ecology of purified waters and discusses the impacts of biological activity on industrial systems. PMID- 26879944 TI - A stumbling block or a stepping stone? PMID- 26879943 TI - [In order to see clearly it is often sufficient just to change the perspective]. PMID- 26879945 TI - A stumbling block or a stepping stone? PMID- 26879946 TI - Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients. AB - BACKGROUND: Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS). METHODS: For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS. RESULTS: MACE occurred in 23 patients (1.5 %): death (3, 0.2 %), myocardial infarction (4, 0.3 %) and late revascularisation (16, 1.3 %). Multivariate analysis showed an independent prognostic value of CCTA (p < 0.001), CACS of 100-400 (p = 0.035) and CACS of > 400 (p = 0.021). CCTA showed obstructive CAD in 3.1 % of patients with CACS = 0. No events occurred in patients with CACS = 0 without obstructive CAD at CCTA, whereas 2/23 patients (9 %) with CACS = 0 with obstructive CAD had a MACE. CONCLUSIONS: Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS = 0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE. PMID- 26879948 TI - Are severe hypoglycemic episodes in diabetes correctly identified by administrative data? Evidence of underreporting from the HYPOTHESIS study. PMID- 26879947 TI - Living in the Now: Decision-Making and Delay Discounting in Adolescent Gamblers. AB - Several studies examining the relationship of affective decision-making and delay discounting in disordered gambling demonstrated that adult pathological gamblers differ from healthy controls on both reward-related decision tasks. To date no study analyzed the relative contribution of these variables in adolescent gambling. This study was designed to compare affective decision-making and delay discounting in gamblers and nongamblers Italian adolescents, controlling for alcohol consumption. A total of 138 adolescents took part in the research. Two equal-number groups, defined according to the scoring rules for the South Oaks Gambling Screen-Revised for Adolescents, were administered the Iowa Gambling Task (IGT), the Monetary Choice Questionnaire (MCQ), and the Alcohol Use Disorders Identification Test (AUDIT). Zero-order correlations among all variables revealed a moderate negative association between IGT and MCQ scores only in nongamblers group. Results of mixed-model ANOVAs indicated that, compared with nongamblers, adolescent gamblers performed worse on the IGT, showed steeper delay discounting, and scored significantly higher on the AUDIT. Results of logistic regression analysis indicated that IGT, MCQ, and AUDIT scores are all significant predictors of gambling status. This novel finding provides the first evidence of an association among problematic gambling, maladaptive decision-making, and steep delay discounting among adolescents, as already observed in adults. PMID- 26879949 TI - Accidental exposures to blood and body fluids among health care workers in a Referral Hospital of Cameroon. AB - BACKGROUND: Accidental exposure to blood and body fluids is a public health concern, especially among health workers and constitutes a risk of transmission of blood-borne viruses including HIV, hepatitis B virus and hepatitis C virus. The objective of this study was to determine the frequency and the post exposure management of accidental exposures to blood and body fluid among health workers in the Yaounde University Teaching Hospital. METHODS: It was a cross-sectional hospital-based study conducted from the 1st to the 30th of September 2013. Self administered questionnaires to health workers were used to collect data on self reported accidents, circumstances and post-exposure management. Their knowledge on accidental exposure to blood was also assessed. Data were entered and analyzed using Epi Info software version 3.5.4. Descriptive analysis was performed to measure the importance of AEB and to evaluate the risk of contamination. RESULTS: One hundred and fifty health workers were interviewed among which 36.7 % reported having been exposed to blood and body fluid at least once in the preceding 3 months. Splash was the most reported injury (in 60.3 % of cases), followed by needle stick (28.7 %) and cuts (10.9 %). Moreover, 43.6 % of victims were not vaccinated against HBV, 7.3 % were not wearing gloves during the accident and 41 % of splash occurs on injured skin. The majority of victims belong to the surgical Department [20 %, p = 0.2310]. None of these injuries had been reported in the registry of accidental exposure to blood. CONCLUSIONS: There is a high rate of accidental exposure to blood and body fluid in the daily hospital routine. Preventives measures, including wearing of protective equipment's during care and vaccination against HBV are not systematically done among health workers. Health institution should develop and provide standard operating procedures targeting surveillance of occupational risks, staff training, and supervision. PMID- 26879951 TI - Validating mammalian resistance to stressor-mediated reproductive impact using rodent sperm analysis. AB - Small rodents from chemically and radiologically contaminated areas on the Savannah River Site, SC were evaluated for sensitive reproductive parameters in a dual purpose study. The primary intent was to observe if established reproductive thresholds-for effect could be exceeded in animals that, due to their restricted home ranges, are maximally exposed to local contamination. Secondarily, validation was sought for a principal element of the Rodent Sperm Analysis method that is used in support of ecological risk assessments for contaminated terrestrial properties. The method's fundamental underlying premise is that during decades of elapsed time between contamination release events and ecological assessments being conducted, rodents develop a resilience to potential stressors, evidenced by their continuing presence. During spring 2014 we collected 89 cotton mice (Peromyscus gossypinus) across three contaminated locations and one reference location, and quantified important male and female reproductive parameters (sperm counts and sperm morphology, and ovarian follicle counts, respectively) and organ weights. The outcome of the comprehensive sperm parameter review, in conjunction with the parallel female reproduction review and other corroborative population and tissue-based information gathered, suggests that mammalian assessments at contaminated sites are unnecessary in the common case. PMID- 26879950 TI - Neonatal Abstinence Syndrome in West Virginia Substate Regions, 2007-2013. AB - PURPOSE: The opioid epidemic is a public health threat with consequences affecting newborns. Neonatal Abstinence Syndrome (NAS) is a constellation of withdrawal symptoms resulting primarily from in utero opioid exposure. The purpose of this study was to examine NAS and drug-specific trends in West Virginia (WV), where rurality-related issues are largely present. METHODS: The 2007-2013 WV Health Care Authority, Uniform Billing Data were analyzed for 119,605 newborn admissions with 1,974 NAS diagnoses. NAS (ICD9-CM 779.5) and exposure diagnostic codes for opioids, hallucinogens, and cocaine were utilized as incidence rate (IR) per 1,000 live births. FINDINGS: Between 2007 and 2013, NAS IR significantly increased from 7.74 to 31.56 per 1,000 live births per year (Z: -19.10, P < .0001). During this time period, opioid exposure increased (Z: 9.56, P < .0001), while cocaine exposure decreased (Z: 3.62, P = .0003). In 2013, the southeastern region of the state had the highest NAS IR of 48.76 per 1,000 live births. NAS infants were more likely to experience other clinical conditions, longer hospital stay, and be insured by Medicaid. CONCLUSIONS: Statewide NAS IR increased 4-fold over the study period, with rates over 3 times the national annual averages. This alarming trend is deleterious for the health of WV mother-child dyads and it strains the state's health care system. Therefore, WV has a unique need for prenatal public health drug treatment and prevention resources, specifically targeting the southeastern region. Further examination of maternal drug-specific trends and general underutilization of neonatal exposure ICD-9-CM codes is indicated. PMID- 26879953 TI - Molecular serotyping and antimicrobial resistance profiles of Actinobacillus pleuropneumoniae isolated from pigs in South Korea. AB - BACKGROUND: Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PP). OBJECTIVE: Serotypes and antimicrobial resistance patterns in APP isolates from pigs in Korea were examined. METHODS: Sixty-five APP isolates were genetically serotyped using standard and multiplex PCR (polymerase chain reaction). Antimicrobial susceptibilities were tested using the standardized disk agar method. PCR was used to detect beta-lactam, gentamicin and tetracycline resistance genes. The random amplified polymorphic DNA (RAPD) patterns were determined by PCR. RESULTS: Korean pigs predominantly carried APP serotypes 1 and 5. Among 65 isolates, one isolate was sensitive to all 12 antimicrobials tested in this study. Sixty-two isolates was resistant to tetracycline and 53 isolates carried one or five genes including tet(B), tet(A), tet(H), tet(M)/tet(O), tet(C), tet(G) and/or tet(L)-1 markers. Among 64 strains, 9% and 26.6% were resistance to 10 and three or more antimicrobials, respectively. Thirteen different antimicrobial resistance patterns were observed and RAPD analysis revealed a separation of the isolates into two clusters: cluster II (6 strains resistant to 10 antimicrobials) and cluster I (the other 59 strains). CONCLUSION: Results show that APP serotypes 1 and 5 are the most common in Korea, and multi drug resistant strains are prevalent. RAPD analysis demonstrated that six isolates resistant to 10 antimicrobials belonged to the same cluster. PMID- 26879952 TI - Involvement of hormones in olfactory imprinting and homing in chum salmon. AB - The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker. PMID- 26879954 TI - The association between MTHFR polymorphisms and cervical cancer risk: a system review and meta analysis. AB - PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) plays an important role in determining the proportions of folate coenzymes for DNA synthesis or DNA methylation. Published data on the association between the MTHFR polymorphisms and cervical risk are controversial. A meta-analysis was performed to assess whether the polymorphisms of MTHFR are associated with cervical cancer risk. METHODS: Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases were searched to identify eligible studies. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) for MTHFR C677T and MTHFR A1298C polymorphisms and cervical cancer were appropriately derived from fixed-effects or random effects models. Five different ORs were calculated: (1) allele contrast (C vs. T), (2) homozygous comparison (CC vs. TT), (3) heterozygous comparison (CC vs. CT), (4) dominant model (CC vs. CT+TT) and (5) recessive model (CC+CT vs. TT). RESULTS: A total of 13 studies, which included 12 studies for MTHFR C677T (2332 cases and 3000 controls) and five studies for A1298C polymorphisms (677 cases and 1191 controls), were enrolled in this meta-analysis. The pooled analyses revealed that MTHFR C677T polymorphism was not associated with cervical cancer risk; while the A1298C polymorphism had a significant association with increased cervical cancer risk in allele contrast, heterozygote comparison and dominant model (A C, OR = 0.84, 95 % CI = 0.71-0.98; AA vs. CC OR = 0.72, 95 % CI = 0.59-0.89; AA vs. AC+CC, OR = 0.72, 95 % CI = 0.59-0.88). The significant associations between MTHFR A1298C polymorphism and cervical cancer were found among Asians and population-based case-control studies. CONCLUSIONS: This study indicated that the MTHFR C677T may be no associated with cervical cancer risk, and yet the MTHFR A1298C polymorphism may be a risk factor for cervical cancer. PMID- 26879956 TI - Location, location, location: Validating the position of deep brain stimulation electrodes. PMID- 26879955 TI - Deep-sequencing identification of differentially expressed miRNAs in decidua and villus of recurrent miscarriage patients. AB - PURPOSE: MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene expression regulation. The aim of this study was to identify differentially expressed miRNAs in decidua and villus of recurrent miscarriage (RM) patients. METHODS: Participants were recruited at the outpatient Department of Gynecology and Obstetrics, The Second Hospital of Tianjin Medical University, China. Decidua and villus tissues were collected by curettage from recruited RM patients and normal pregnant women with their informed consent. MiRNAs expression profiles in decidua or villus were respectively determined by the deep-sequencing analysis. The predicated target genes of these differentially expressed miRNAs were analyzed by miRWalk. The differential expressions of four miRNAs in decidua and four miRNAs in villus between the six pairs of RM patients and normal pregnant women were confirmed by qRT-PCR analysis. The expression patterns of two predicated target genes, Bcl-2 and Pten, in the same six pairs of decidual or villus tissues were detected by Western blotting analysis, respectively. RESULTS: Totally 18 RM patients and 15 normal pregnant women were recruited. Thirty-two miRNAs in decidua and four miRNAs in villus of RM patients were screened out to be significantly up regulated compared to that of normal pregnant women, and five miRNAs in villus of RM patients were screened out to be remarkably down-regulated compared to that of normal pregnant women (P value < 0.05 and Fold change >2). These differentially expressed miRNAs were predicted to target a large number of genes that involved in cell apoptosis, p53 signaling pathway, cell cycle and other cellular bio functions. Differential expressions of hsa-miR-516a-5p, -517a-3p, -519a-3p and 519d in decidua, as well as hsa-miR-1, -372, -100-5p and -146a-5p in villus, were validated by qRT-PCR analysis. In the decidual of RM patients, expression of hsa miR-516a-5p, -517a-3p, -519a-3p and -519d were significantly up-regulated compared to normal pregnancy. In the villi of RM patients, expression of hsa-miR 100 and -146a-5p were significantly higher, while hsa-miR-1 and -372 were significantly lower compared to normal pregnancy. Furthermore, the expression of Bcl-2 and Pten, a predicated target gene of hsa-miR-1 or hsa-miR-372 respectively, was significantly up-regulated in the villi of RM patients. CONCLUSIONS: These data suggested that the pathogenic process of RM might be associated with the alteration of miRNAs expression profiles in decidua and villus. Especially, the aberrant placental expression of hsa-miR-1 and -372 might be involved in the progression of RM, but need to be further investigated by larger studies in the future. PMID- 26879957 TI - Multiple effects of trace elements on methanogenesis in a two-phase anaerobic membrane bioreactor treating starch wastewater. AB - For enhancing anaerobic membrane bioreactor (AnMBR) treating food processing wastewater due to speed-limited methanogenesis step, multiple effects of trace element (TE) supplementation on methanogenesis of a two-phase AnMBR were firstly investigated in batch tests. TE supplementation included individual element, combination and recovery of Fe, Ni, Co, Cu and Zn supplementation. Multiple effects of TE supplementation were highest stimulated by 22.4 +/- 5.6 % (TE313) for chemical oxygen demand (COD) removal, 43.1 +/- 12.5 % (TE303) for specific methanogenic activity (SMA) and 13.9 +/- 3.7 % (TE405) for biomass growth, respectively, although only 7.5 +/- 0.6 % (TE106) for methane production. Dosage of TEs played a critical role in methane production, COD removal and biomass growth of the AnMBR's methanogenesis. Low dosages of TE supplementation improved the COD removal and slightly stimulated the COD bioconverting to methane and biomass, but their specific methanation activities were inhibited in the initial rapid methanogenesis stage. Several methanation functional species were increased in abundance like Methanosarcina and Methanoculleus. PMID- 26879958 TI - Impacts of ruminal microorganisms on the production of fuels: how can we intercede from the outside? AB - The ruminal microbiome rapidly converts plant biomass to short-chain fatty acids (SCFA) that nourish the ruminant animal host. Because of its high species diversity, functional redundancy, and ease of extraruminal cultivation, this mixed microbial community is a particularly accomplished practitioner of the carboxylate platform for producing fuels and chemical precursors. Unlike reactor microbiomes derived from anaerobic digesters or sediments, the ruminal community naturally produces high concentrations of SCFA, with only modest methane production owing to the absence of both proton-reducing acetogens and aceticlastic methanogens. The extraruminal fermentation can be improved by addition of ethanol or lactate product streams, particularly in concert with reverse beta-oxidizing bacteria (e.g., Clostridium kluyveri or Megasphaera elsdenii) that facilitate production of valeric and caproic acids. Application of fundamental principles of thermodynamics allows identification of optimal conditions for SCFA chain elongation, as well as discovery of novel synthetic capabilities (e.g., medium-chain alcohol and alkane production) by this mixed culture system. PMID- 26879959 TI - Insights into conformational regulation of PfMATE transporter from Pyrococcus furiosus induced by alternating protonation state of Asp41 residue: A molecular dynamics simulation study. AB - BACKGROUND: Multidrug and toxic compound extrusion (MATE) family transporters induce multiple-drug resistance (MDR) of bacterial pathogens and cancer cells, thus causing critical reductions in the therapeutic efficacies of antibiotics and anti-cancer drugs. Unfortunately, to date, the details and intrinsic reason about conformational regulation mechanism of MATE transporters remain elusive. METHOD: In this work, molecular dynamics (MD) simulations were conducted to explore the conformational regulation mechanism of PfMATE transporter from Pyrococcus furiosus based on different protonation state of Asp41. Two (MD) simulation systems were investigated: a system with protonation of Asp41 and a system without protonation of Asp41, which were named by D184(H)D41(H) system and D184(H) system, respectively. RESULTS AND CONCLUSIONS: Firstly, MD simulation results indicate that conformational changes mainly happen in extracellular regions of PfMATE protein. Further analysis reveals that PfMATE protein experiences different motion mode and forms different conformation based on different protonation state of Asp41. In the D184(H)D41(H) system, PfMATE experiences an opening motion and forms a more outward-open conformation. As for the D184(H) system, the protein has an anticlockwise rotational motion with the channel axis of protein and the more outward-open conformation does not appear. It can be inferred that protonation of Asp41 is essential for conformational regulation of PfMATE during transporting substrates. GENERAL SIGNIFICANCE: These findings provide intrinsic information for understanding the conformational regulation mechanism of PfMATE and will be very meaningful to explore the MDR mechanism of PfMATE further. PMID- 26879960 TI - In Silico Analysis of the Structure of Fungal Fructooligosaccharides-Synthesizing Enzymes. AB - Fructooligosaccharides (FOS) are prebiotics commonly manufactured using fungal fructosyltransferases (FTases) or beta-fructofuranosidases. Several reports have attempted to optimize FOS production by changing operational conditions. Nevertheless, there is a lack of information related to the molecular enzyme substrate interaction. In this study, we present an in silico evaluation of the interactions between substrates (i.e., glucose, sucrose, GF2, GF3, and GF4) and native FOS-synthesizing enzymes from fungi, with reported FOS production yield. In addition, a molecular dynamic simulation was conducted to assess the stability of these interactions. Six fungal enzymes with reported data of FOS production were selected: sucrose-sucrose 1-fructosyltransferase from A. foetidus (GenBank No. CAA04131); intracellular invertase from A. niger (GenBank No. ABB59679); extracellular invertase from A. niger (GenBank No. ABB59678); beta fructofuranidase from A. japonicus ATCC 20611 (GenBank No. BAB67771); fructosyltransferase from A. oryzae N74 (GenBank No. ACZ48670); and fructosyltransferase from A. japonicus (PDB ID 3LF7). These enzymes shared an identity between 15 and 96 %, but have a highly conserved folding, and the characteristic FTases domains. Docking results showed that these enzymes also share a similar protein-ligand interaction profile. It was observed that the production yield of total FOS correlated with the sum of affinity energies for GF2, GF3, and GF4. Finally, we present the first molecular dynamic simulation for FOS and fungal FOS-synthesizing enzymes, showing that the protein-ligand interaction does not induce significant changes on the enzyme stability. Overall, these results represent valuable information to continue understanding the FOS synthesis process by fungal FOS-synthesizing enzymes, and they can have a significant impact toward the improvement in their catalytic properties and the synthesis of specific FOS. PMID- 26879961 TI - Enhanced Prediction and Characterization of CDK Inhibitors Using Optimal Class Distribution. AB - Cyclin-dependent kinase inhibitors (CDKIs) govern the regulation of cyclin dependent kinases, which are responsible for controlling cell cycle progression. The members of the CDKI protein family play important roles in many processes like tumor suppression, apoptosis, transcriptional regulation. The sequence similarity-based search methods to annotate putative CDKIs do not yield optimal performance due to sequence diversity of CDKIs. As a consequence, machine learning-based models have become viable choices for predicting CDKI. In this work, we have developed a framework for handling the class imbalance factor (which is encountered very frequently in biological datasets) in order to enhance the prediction of CDKI through machine learning approaches. We have designed our experiments to achieve the optimal performance of machine learning-based methods in predicting CDKI by investigating the dataset-related prediction enhancement issues, like: (1) What should be the optimal class distribution ratio in the training set? (2) Should we oversample or undersample? (3) At what ratio, positive and negative samples should be oversampled or undersampled? and (4) How to select the best-performing classifier? We have addressed these issues through comparing the results from an imbalanced training set with training sets which are created at different resampling rates by using synthetic minority over sampling technique and undersampling technique to have varied class distributions. The proposed framework resulted in 100 % sensitivity, 93.7 % specificity, 96.4 % accuracy, 0.929 MCC with 0.981 AUC using simple sequence based features on a leave-one-out cross-validation test. The generalization ability of the trained model was further tested on four separate blind testing sets. Our work supports the fact that the performance of the algorithms can be enhanced by creating an optimal class distribution in the training set besides fine-tuning of the parameters of the algorithms. This optimal ratio of positive and negative samples in the training set is an important learning enhancement parameter for prediction models based on machine learning algorithms. PMID- 26879962 TI - Incidence of dementia declined in past 30 years in US, study shows. PMID- 26879963 TI - The first Mesozoic microwhip scorpion (Palpigradi): a new genus and species in mid-Cretaceous amber from Myanmar. AB - A fossil palpigrade is described and figured from mid-Cretaceous (Cenomanian) amber from northern Myanmar. Electrokoenenia yaksha Engel and Huang, gen. n. et sp. n., is the first Mesozoic fossil of its order and the only one known as an inclusion in amber, the only other fossil being a series of individuals encased in Pliocene onyx marble and 94-97 million years younger than E. yaksha. The genus is distinguished from other members of the order but is remarkably consistent in observable morphological details when compared to extant relatives, likely reflecting a consistent microhabitat and biological preferences over the last 100 million years. PMID- 26879966 TI - Editorial. PMID- 26879965 TI - Energy Drink Use Among Ohio Appalachian Smokers. AB - Caffeine-containing energy drinks have emerged as a public health concern due to their association with caffeine toxicity and alcohol use. Despite the fact that previous research has linked caffeine use in the form of coffee drinking to smoking, there is little research examining the association between energy drinks and smoking. The present study examines demographic and behavioral factors associated with energy drink use among a sample of rural Ohio Appalachian smokers. It was hypothesized that male gender, young age (21-30 years.) and alcohol use would be associated with energy drink use. A sample of adult smokers (n = 298) from Ohio Appalachian counties were interviewed regarding demographic and behavioral factors. Logistic regression analysis was used to assess the association between these factors and energy drink use. Seventy percent of Ohio Appalachian smokers studied had ever used an energy drink and 40 % had used an energy drink in the past month. Young age, male gender, and single marital status were associated with higher odds of ever having used an energy drink. Young age, and binge drinking were associated with higher odds of past 30-day use while abstinence from drinking was associated with lower odds of past 30-day use. Ohio Appalachian adult smokers had higher rates of energy drink use compared to previous estimates of ever or past month use found in other studies. The combined use of caffeine, nicotine, and alcohol warrants attention due to potential for health risk. PMID- 26879964 TI - Sarcopenia-related features and factors associated with lower muscle strength and physical performance in older Chinese: a cross sectional study. AB - BACKGROUND: The associations of sarcopenia with adverse health status have highlighted the importance of sarcopenia research and intervention. This study was designed to analyze the characteristics of aging-related differences in appendicular skeletal muscle mass (ASM), handgrip strength (HS), gait speed (GS) and their associated factors in older Chinese, in order to generate guidance for sarcopenia intervention in this population. METHODS: Population-based cross sectional study. The criteria proposed by Asian Working Group for Sarcopenia were used to define low ASM, HS, and GS. The time required for five repeated chair stands (RCS) was also measured to evaluate physical performance. The differences of continuous variables were compared using one-way ANOVA tests and the Pearson correlation was used to analyze the relationship of each measurement adjusted by gender and age. Stepwise logistic regression was used to determine associated factors of low HS and low physical performance. RESULTS: The data were analyzed in a total of 218 younger adults (aged 20-59, 76 males, 142 females) and 461 older adults (>=60 year, 207 males and 254 females). There were significant differences among age groups for HS, GS, and RCS while females were found to have significantly lower HS and GS values. ASM was significantly correlated with HS but not with other measures. Correlations among HS and GS, RCS were influenced by age differences. In the older group, unstructured daily routine (OR = 2.77) was associated with the risk of low GS, while physical exercise (OR = 0.27), and engaging in hobbies (OR = 0.11) were associated with faster GS. Co-morbidity (OR = 1.99) was associated with the risk of reduced performance of RCS, while engaging in hobbies was associated with faster RCS performance (OR = 0.35). CONCLUSIONS: Muscle strength and physical performance varied with aging in older Chinese. Measures of GS, HS, and RCS provide a readily available and effective method for assessing the risk of functional mobility decline. Maintaining a healthy life style and physical activity throughout life is beneficial for older people to improve their physical performance, especially in the early stages of aging. PMID- 26879968 TI - [Lung ultrasound in the newborn]. AB - Lung ultrasound (LU) is becoming a bedside point-of-care technique in critical care and emergency medicine as it is performed and immediately interpreted by the clinician. LU is quick, easy, relatively inexpensive, and provides accurate diagnostic information when compared with conventional lung imaging methods, such as CT scans and chest radiographs, with the additional advantage of being non irradiating, adapted to bedside use, and easily repeatable with no side effects for the patient. LU is easy to learn, does not require sophisticated ultrasound machines or settings, and shows low intra- and interobserver variability when a standardized approach is used. A comprehensive and standardized ultrasound semiology has been described and validated in both adults and children. In summary, LU allows for quick easy recognition of a normally aerated lung in contrast to an interstitial or alveolar pattern. Recognition of these patterns may be even easier in neonates due to their small size and the absence of obesity and heavy musculature. Specific LU findings have been described for some types of neonatal lung injury, such as neonatal respiratory distress syndrome, transient tachypnea of the neonate, meconium aspiration syndrome, and neonatal pneumonia. In the newborn, LU has proved its usefulness in predicting the need for hospital admission and/or intubation based on simple LU patterns. A recently proposed LU score, adapted for the neonate, correlates well with oxygenation status, independently of gestational age and underlying respiratory condition. The score reliably predicts the need for surfactant treatment in preterm babies less than 34 weeks gestation treated with nasal CPAP from birth. LU is a promising tool with numerous potential applications that warrant future studies. However, like every technique, LU has its limitations and should not completely replace standard radiography. LU can nevertheless largely reduce exposure to ionizing radiation by limiting the use of conventional radiographs to a strict minimum. PMID- 26879967 TI - [Insulin treatment of gestational diabetes and respiratory outcome in late preterm and term babies]. AB - While the incidence of diabetes mellitus (DM) during pregnancy has been steadily increasing in recent years, the link between gestational DM and respiratory outcome in neonates has not been firmly established. To address this gap in understanding, we asked whether DM status and its treatment during pregnancy influence risk of neonatal respiratory distress. We conducted retrospective analysis of a large cohort to determine the relationship between maternal DM status (non-DM, insulin-treated DM [DTI], and non-insulin-treated DM [DTR]) and respiratory distress in term and near-term singletons, born at Robert-Debre Hospital over a 7-year period. Of 18,095 singletons delivered at 34 weeks of gestation or later, 412 (2.3%) were admitted to the NICU for respiratory distress within the first hours of life. The incidence of NICU admissions due to respiratory distress was 2.2% in the non-DM group, 2.1% in the DTR group, and 5.7% in the DTI group. Insulin treatment of DM, together with several other perinatal factors, was associated with an increased risk for severe respiratory distress. In a multivariate model, we found that DTI, but not DTR, was a risk factor independent of gestational age and cesarean section, with an IRR of 1.44 (95% CI, 1.00-2.08). The data indicate that newborns of mothers with DM treated with diet are not at risk for severe respiratory distress. Conversely, newborns of mothers with DM treated with insulin are associated with elevated risk for severe respiratory disease and should therefore be closely monitored. PMID- 26879969 TI - [Kangaroo mother care for low birth weight infants at Albert-Royer National Children Hospital Center of Dakar]. AB - INTRODUCTION: Kangaroo care (KC) is an effective method to care for low birth weight (LBW) newborns, particularly in developing countries. The objective of this study was to estimate the efficacy of this method and its impact on morbidity and mortality of LBW infants admitted to the KC unit of Albert-Royer National Children's Hospital Center (ARNCHC) in Dakar, Senegal. MATERIAL AND METHODS: This was a retrospective, single-center study from July 2011 to July 2013. We collected sociodemographic, maternal, and obstetrical data, neonatal characteristics and information during KC (age and weight at inclusion, thermoregulation, feeding, growth, and overall progression). Data were entered and analyzed using SPSS version 9.0. RESULTS: We included 135 newborns, with a female predominance (sex ratio: 0.78). One-third of the mothers (35.5%) were primiparous and only 21.1% had a socioprofessional activity and the majority had a low educational level. The mean gestational age (GA) was 33.08+/-2.06 weeks of amenorrhea and the mean birth weight 1485+/-370 g. There were 20 term babies with intrauterine growth restriction (IUGR) (14.8%) and 115 (85.2%) preterm newborns, 83 (72.2%) of whom, showed IUGR. The mean duration of conventional care was 12.3 days (range: 4-27 days) and the main complications were respiratory distress (46.2%), infection (36.9%), and necrotizing enterocolitis (15.1%). At KC admission, the mean post-conceptional age was 34.2+/-2.46 weeks and the mean weight 1445+/-319 g (minimum, 700 g). The main complications in KC were infections (20.2%), hypoglycemia (18.5%), and gastro-esophageal reflux disease (16.4%). Only 56.3% of the babies were exclusively breastfed. The mean weight gain during the stay in the KC unit was 15.3+/-9.08 g/kg/day and the mean weight at discharge was 1761+/-308 g. Only three episodes of hypothermia were noted. The mean duration in the KC unit was 10.2 days (range: 3-24 days). Five babies died (3.7%): one during KC, one at home, and the three others after readmission to neonatology. CONCLUSION: Kangaroo care for LBW infants is highly effective in our context. This method should be spread to a large majority of health centers in the country. PMID- 26879970 TI - Retraction Note: Notice of formal retraction of articles by Dr. Akihiro Cho. PMID- 26879973 TI - Connecting the dots on health inequalities--a systematic review on the social determinants of health in Portugal. AB - INTRODUCTION: Health inequalities are recognised as a public health issue worldwide, but only a few countries have developed national strategies to monitor and reduce them. Despite its considerable health inequalities, Portugal seems to lack a systematic strategy to tackle them, possibly due to the absence of organised evidence on the issue. We performed a systematic review that aimed to describe the available evidence on social inequalities in health in Portugal, in order to contribute towards a comprehensive and focused strategy to tackle them. METHODS: We followed the PRISMA guidelines and searched Scopus, Web of Science and PubMed for studies that looked at the association between a measure of socioeconomic status and a health outcome in the Portuguese resident population since the year 2000. We excluded health behaviours and healthcare use from our search. We performed a qualitative description of the results. RESULTS: Seventy one publications were selected, all reporting observational analyses, most of them using cross-sectional data. These publications showed strong evidence for health inequalities related to education and gender, chiefly for obesity, self rated health and mental health. CONCLUSIONS: Analysis of the eligible publications showed that current research does not seem to have consistently covered the link between health and key Portuguese social problems. A strategy focusing on the monitoring of most prevalent diseases, most determining socioeconomic factors and vulnerable populations would be crucial to guide academic research in a country in which health inequalities are so ubiquitous and deeply rooted. REGISTRATION: This systematic review is not registered. PMID- 26879972 TI - Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry. AB - BACKGROUND: There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. METHODS: This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. RESULTS: Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. CONCLUSION: Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts. PMID- 26879974 TI - HIV-1 Vaccine-elicited Antibodies Reverted to Their Inferred Naive Germline Reveal Associations between Binding Affinity and in vivo Activation. AB - The elicitation of HIV-1 broadly neutralizing antibodies following envelope glycoprotein (Env) vaccination is exceedingly difficult. Suboptimal engagement of naive B cells is suggested to limit these low frequency events, especially at the conserved CD4bs. Here, we analyzed CD4bs-directed monoclonal antibodies (mAbs) elicited by YU2 gp140-foldon trimers in a non-human primate by selective sorting using CD4bs "knock out" trimers. Following two inoculations, the CD4bs-directed mAbs efficiently recognized the eliciting immunogen in their affinity-maturing state but did not recognize CD4bs-defective probes. We reverted these mAbs to their most likely inferred germline (igL) state, leaving the HCDR3 unaltered, to establish correlates of in vitro affinity to in vivo activation. Most igL reverted mAbs bound the eliciting gp140 immunogen, indicating that CD4bs-directed B cells possessing reasonable affinity existed in the naive repertoire. We detected relatively high affinities for the majority of the igL mAbs to gp120 and of Fabs to gp140, which, as expected, increased when the antibodies 'matured' following vaccination. Affinity increases were associated with slower off-rates as well as with acquisition of neutralizing capacity. These data reveal in vitro binding properties associated with in vivo activation that result in functional archiving of antigen-specific B cells elicited by a complex glycoprotein antigen following immunization. PMID- 26879975 TI - Genome-wide transcriptional regulation of estrogen receptor targets in fallopian tube cells and the role of selective estrogen receptor modulators. AB - BACKGROUND: The fallopian tube epithelium is one of the potential sources of high grade serous ovarian cancer (HGSC). The use of estrogen only hormone replacement therapy increases ovarian cancer (OVCA) risk. Despite estrogen's influence in OVCA, selective estrogen receptor modulators (SERMs) typically demonstrate only a 20 % response rate. This low response could be due to a variety of factors including the loss of estrogen receptor signaling or the role of estrogen in different potential cell types of origin. The response of fallopian tube epithelium to SERMs is not known, and would be useful when determining therapeutic options for tumors arising from this cell type, such as HGSC. RESULTS: Using normal murine derived oviductal epithelial cells (mouse equivalent to the fallopian tube) estrogen receptor expression was confirmed and interaction with its ligand, estradiol, triggered mRNA and protein induction of progesterone receptor (PR). The SERMs 4-hydroxytamoxifen, raloxifene and desmethylarzoxifene, functioned as estrogen receptor antagonists in oviductal cells. Cellular proliferation and migration assays suggested that estradiol does not significantly impact cellular migration and increased proliferation. Further, using RNAseq, the oviduct specific transcriptional genes targets of ER when stimulated by estradiol and 4-hydroxytamoxifen signaling were determined and validated. The RNA-seq revealed enrichment in proliferation, anti-apoptosis, calcium signaling and steroid signaling processes. Finally, the ER and PR receptor status of a panel of HGSC cell lines was investigated including Kuramochi, OVSAHO, OVKATE, OVCAR3, and OVCAR4. OVSAHO demonstrated receptor expression and response, which highlights the need for additional models of ovarian cancer that are estrogen responsive. CONCLUSIONS: Overall, the fallopian tube has specific gene targets of estrogen receptor and demonstrates a tissue specific response to SERMs consistent with antagonistic action. PMID- 26879976 TI - Development of a Cell Marker ELISA for the Detection of Goose T Cell Surface CD8alpha Molecules. AB - CD8 molecule is a key marker on T cell surface and is connected with the antigen recognition and activation of T lymphocytes. In order to provide a detection method for quantifying goose CD8alpha expression, this study raised the protein and antibody for goose CD8alpha and developed a feasible cell marker enzyme linked immunoabsorbent assay (ELISA) method. Recombinant protein of the extracellular region gene of goCD8alpha was expressed in prokaryotic expression system, and specific polyclonal antibodies for goCD8alpha were raised and purified, which was further confirmed by Western-blot, immunofluorescence assay (IFA), and immunohistochemistry (IHC). A cell marker ELISA was established and optimized to detect the change of goCD8alpha expression between goose parvovirus (GPV)-infected and mock-infected goose peripheral blood mononuclear cells (PBMCs), which is consistent with our previously results of real-time quantitative PCR (qPCR). Cell marker ELISA can provide a new method to detect goCD8alpha in protein level and in a sensitive, specific, and simple way. This may provide a convenient and novel method for the detection of goCD8alpha expression. PMID- 26879977 TI - A Novel Method for Efficient Preparation of Mucosal Adjuvant Escherichia coli Heat-Labile Enterotoxin Mutant (LTm) by Artificially Assisted Self-Assembly In Vitro. AB - As well-known powerful mucosal adjuvant proteins, Escherichia coli heat-labile enterotoxin (LT) and its non-toxic or low-toxic mutants (LTm) are capable of promoting strong mucosal immune responses to co-administered antigens in various types of vaccines. However, due to the complex composition and special structure, the yield of LTm directly from the recombinant genetic engineering strains is quite low. Here, we put forward a novel method to prepare LTm protein which designed, expressed, and purified three kinds of component subunits respectively and assembled them into a hexamer structure in vitro by two combination modes. In addition, by simulated in vivo environment of polymer protein assembly, the factors of the protein solution system which include environment temperature, pH, ionic strength of the solution, and ratio between each subunit were taken into consideration. Finally, we confirmed the optimal conditions of two assembly strategies and prepared the hexamer holotoxin in vitro. These results are not only an important significance in promoting large-scale preparation of the mucosal adjuvant LTm but also an enlightening to produce other multi-subunit proteins. PMID- 26879978 TI - GH53 Endo-Beta-1,4-Galactanase from a Newly Isolated Bacillus licheniformis CBMAI 1609 as an Enzymatic Cocktail Supplement for Biomass Saccharification. AB - Galactanases (endo-beta-1,4-galactanases-EC 3.2.1.89) catalyze the hydrolysis of beta-1,4 galactosidic bonds in arabinogalactan and galactan side chains found in type I rhamnogalacturan. The aim of this work was to understand the catalytic function, biophysical properties, and use of a recombinant GH53 endo-beta-1,4 galactanase for commercial cocktail supplementation. The nucleotide sequence of the endo-beta-1,4-galactanase from Bacillus licheniformis CBMAI 1609 (Bl1609Gal) was cloned and expressed in Escherichia coli, and the biochemical and biophysical properties of the enzyme were characterized. The optimum pH range and temperature of Bl1609Gal activity were 6.5-8 and 40 degrees C, respectively. Furthermore, Bl1609Gal showed remarkable pH stability, retaining more than 75 % activity even after 24 h of incubation at pH 4-10. The enzyme was thermostable, retaining nearly 100 % activity after 1-h incubation at pH 7.0 at 25-45 degrees C. The enzymatic efficiency (K cat /K m ) against potato galactan under optimum conditions was 241.2 s(-1) mg(-1) mL. Capillary zone electrophoresis demonstrated that the pattern of galactan hydrolysis by Bl1609Gal was consistent with that of endogalactanases. Supplementation of the commercial cocktail ACCELLERASE((r))1500 with recombinant Bl1609Gal increased hydrolysis of pretreated sugarcane bagasse by 25 %. PMID- 26879979 TI - The serum angiotensin converting enzyme and lysozyme levels in patients with ocular involvement of autoimmune and infectious diseases. AB - BACKGROUND: Increased serum levels of angiotensin converting enzyme and lysozyme are considered as inflammatory markers for diagnosis of sarcoidosis which is an autoimmune inflammatory disease. The purpose of this study is to evaluate the significance of differences in serum angiotensin converting enzyme and lysozyme levels of patients with ocular involvement of other autoimmune inflammatory and infectious diseases. METHODS: This is a prospective study involving patients with ankylosing spondylitis, behcet's disease, presumed sarcoidosis, presumed latent tuberculosis, presumed latent syphilis, and control group. The serum levels of angiotensin converting enzyme and lysozyme were analyzed by enzyme-linked immunosorbent assay. Bonnferoni analysis was used to assess pairwise comparisons between the groups. RESULTS: There was a significant increase in serum angiotensin converting enzyme level in patients with presumed sarcoidosis compared to ankylosing spondylitis (p = 0.0001), behcet's disease (p = 0.0001), presumed latent tuberculosis (p = 0.0001), presumed latent syphilis (p = 0.0001), and control group (p = 0.0001). The increase in serum lysozyme level was significant for patients with presumed sarcoidosis with respect to ankylosing spondylitis (p = 0.0001), behcet's disease, (p = 0.0001) presumed latent tuberculosis (p = 0.001), presumed latent syphilis (p = 0.033), and control group (p = 0.0001). CONCLUSION: Elevated serum angiotensin converting enzyme levels are significant for patients with presumed sarcoidosis compared to ocular involvement of other autoimmune diseases such as behcet's disease and ankylosing spondylitis, and ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. However, elevated serum lysozyme level might be also detected in ocular involvement of infectious diseases such as presumed latent tuberculosis and presumed latent syphilis. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: NCT02627209. Date of registration: 12/09/2015. PMID- 26879980 TI - Ammonia oxidizing bacteria and archaea in horizontal flow biofilm reactors treating ammonia-contaminated air at 10 degrees C. AB - The objective of this study was to demonstrate the feasibility of novel, Horizontal Flow Biofilm Reactor (HFBR) technology for the treatment of ammonia (NH3)-contaminated airstreams. Three laboratory-scale HFBRs were used for remediation of an NH3-containing airstream at 10 degrees C during a 90-d trial to test the efficacy of low-temperature treatment. Average ammonia removal efficiencies of 99.7 % were achieved at maximum loading rates of 4.8 g NH3 m(3) h(-1). Biological nitrification of ammonia to nitrite (NO2 (-)) and nitrate (NO3 (-)) was mediated by nitrifying bacterial and archaeal biofilm populations. Ammonia-oxidising bacteria (AOB) were significantly more abundant than ammonia oxidising archaea (AOA) vertically at each of seven sampling zones along the vertical HFBRs. Nitrosomonas and Nitrosospira, were the two most dominant bacterial genera detected in the HFBRs, while an uncultured archaeal clone dominated the AOA community. The bacterial community composition across the three HFBRs was highly conserved, although variations occurred between HFBR zones and were driven by physicochemical variables. The study demonstrates the feasibility of HFBRs for the treatment of ammonia-contaminated airstreams at low temperatures; identifies key nitrifying microorganisms driving the removal process; and provides insights for process optimisation and control. The findings are significant for industrial applications of gas oxidation technology in temperate climates. PMID- 26879981 TI - Relationships Between Health Behaviors, Self-Efficacy, and Health Locus of Control of Students at the Universities of the Third Age. AB - BACKGROUND This study aimed to determine the relationship of health behaviors with the health locus of control and the sense of self-efficacy against the background of socio-economic factors and self-rated health among students of the Universities of the Third Age (U3As). MATERIAL AND METHODS The study included 320 U3A students, with mean age of 67.5 years. The following research tools were used: Health Behavior Inventory (HBI), Multidimensional Health Locus of Control Scale (MHLC), Generalized Self-Efficacy Scale (GSES), and an original survey of the author's own design. RESULTS Mean total HBI and GSES scores were 90.63 and 30.12, respectively. These results are satisfactory. A slight predominance of internal health locus of control was documented. A number of significant correlations were found between the HBI, GSES, and MHLC scores, except for the MHLC subscale expressing the influence of chance. Educational attainment was shown to have a significant impact on the scores for the positive attitude and proper dietary habits subscales of HBI, as well as on the GSES scores. Economic status of the participants influenced the levels of positive attitude, internal health locus of control, and self-efficacy. Furthermore, internal health locus of control was found to be modulated by subjective health of the respondents. The scores for external health locus of control and the influence of chance increased significantly with age. CONCLUSIONS The currently noticeable emphasis placed on lifelong education should serve as a good prognostic factor for health behaviors and personal health resources for years to come. PMID- 26879983 TI - Distribution and risks of polycyclic aromatic hydrocarbons in suburban and rural soils of Beijing with various land uses. AB - We investigated the sources, distribution, and health risks of polycyclic aromatic hydrocarbons (PAHs) in soils of peri-urban Beijing. The mean concentrations of total 16 PAHs in suburban and rural soils of Beijing were 321.8 +/- 408.2 and 219.2 +/- 233.5 ng/g, respectively. The PAH concentrations decreased along the urban-suburban-rural gradient and varied with land use categories. The industrial areas had the highest soil PAH concentrations followed by the living areas, roadsides, green areas, and agricultural areas. The major sources of PAHs in these soils were coal and biomass combustion. Traffic emission was not the dominant source of PAHs in peri-urban Beijing. At a few sites, high soil PAH contents were caused by point sources such as iron and steel plants and a wood preservative factory. The incremental lifetime cancer risks (ILCRs) of adults and children exposed to PAHs in the soils were acceptable. However, cautions should be paid to the abandoned industrial sites, which might be converted to residential area during the urbanization process. PMID- 26879982 TI - Physiotherapy students' perspectives of online e-learning for interdisciplinary management of chronic health conditions: a qualitative study. AB - BACKGROUND: To qualitatively explore physiotherapy students' perceptions of online e-learning for chronic disease management using a previously developed, innovative and interactive, evidence-based, e-learning package: Rheumatoid Arthritis for Physiotherapists e-Learning (RAP-eL). METHODS: Physiotherapy students participated in three focus groups in Perth, Western Australia. Purposive sampling was employed to ensure maximum heterogeneity across age, gender and educational background. To explore students' perspectives on the advantages and disadvantages of online e-learning, ways to enhance e-learning, and information/learning gaps in relation to interdisciplinary management of chronic health conditions, a semi-structured interview schedule was developed. Verbatim transcripts were analysed using inductive methods within a grounded theory approach to derive key themes. RESULTS: Twenty-three students (78 % female; 39 % with previous tertiary qualification) of mean (SD) age 23 (3.6) years participated. Students expressed a preference for a combination of both online e-learning and lecture-style learning formats for chronic disease management, citing flexibility to work at one's own pace and time, and access to comprehensive information as advantages of e-learning learning. Personal interaction and ability to clarify information immediately were considered advantages of lecture-style formats. Perceived knowledge gaps included practical application of interdisciplinary approaches to chronic disease management and developing and implementing physiotherapy management plans for people with chronic health conditions. CONCLUSIONS: Physiotherapy students preferred multi modal and blended formats for learning about chronic disease management. This study highlights the need for further development of practically-oriented knowledge and skills related to interdisciplinary care for people with chronic conditions among physiotherapy students. While RAP-eL focuses on rheumatoid arthritis, the principles of learning apply to the broader context of chronic disease management. PMID- 26879985 TI - Desertification and its effect on the erosion of vegetation in the south-western region of Saudi Arabia. AB - This study was conducted in Jazan region of south-western Saudi Arabia. Vegetation cover, frequency, abundance and soil characteristics were analysed at three locations with different quantitative and descriptive vegetation characteristics. Plant species were classified into three primary communities dominated by Salvadora persic, Acacia tortilis and Ziziphus spini-Christi. The results indicated that the distribution of plant species is controlled by soil characteristics. Very limited water resources are also limiting factor in vegetation growth. Among the three studied sites, desert and coastal environments are affected by desertification. Rehabilitation of the degraded lands requires collaborative efforts and support from the different related governmental sectors. Ecological conservation and sustainable development must be adopted as tools of rehabilitation. PMID- 26879984 TI - Concentration of Cu, Zn, Cr, Ni, Cd, and Pb in soil, sugarcane leaf and juice: residual effect of sewage sludge and organic compost application. AB - Many researchers have evaluated the effects of successive applications of sewage sludge (SS) on soil plant-systems, but most have not taken into account the residual effect of organic matter remaining from prior applications. Furthermore, few studies have been carried out to compare the effects of the agricultural use of SS and sewage sludge compost (SSC). Therefore, we evaluated the residual effect of SS and SSC on the heavy metal concentrations in soil and in sugarcane (Saccharum spp.) leaves and juice. The field experiment was established after the second harvesting of unburned sugarcane, when the organic materials were applied. The SS and SSC rates were (t ha(-1), dry base): 0, 12.5, 25, and 50; and 0, 21, 42, and 84, respectively. All element concentrations in the soil were below the standards established by Sao Paulo State environmental legislation. SS promoted small increases in Zn concentrations in soil and Cu concentrations in leaves. However, all heavy metals concentrations in the leaves were lower than the limits established for toxic elements and were in accordance with the limits established for micronutrients. There were reductions in the concentrations of Ni and Cu in soil and the concentration of Pb in juice, with increasing rates of SSC. The heavy metal concentrations were very low in the juice. Under humid tropical conditions and with short-term use, SS and SSC containing low heavy metal concentrations did not have negative effects on plants and soil. PMID- 26879986 TI - Dissipation kinetics and risk assessment of thiamethoxam and dimethoate in mango. AB - Thiamethoxam and dimethoate are two insecticides used to control hoppers and inflorescence midges in mango. Thiamethoxam (0.008 and 0.016%) and dimethoate (0.06 and 0.12%) were sprayed on Dashehari mango trees during the pre-mature stage of fruit (first week of May) to study their dissipation kinetics and risk assessment in mango fruit. Thiamethoxam dissipated in fruit from 1.93 and 3.71 mg kg(-1) after 2 h of spraying to 0.08 and 0.13 mg kg(-1) after 20 days of spraying at single and double doses, respectively. Its residue did not persist beyond 20 days in fruit. Dimethoate dissipated in fruit from 2.81 and 5.34 mg kg(-1) after 2 h of application to 0.12 and 0.19 mg kg(-1) after 10 days of application at single and double doses, respectively. No residue was detected in fruit beyond 10 days after its application. Both ready-to-harvest mature mango fruit and pulp (after 40 days of spraying) were free from any residues of these insecticides at both the concentration levels. The rate of dissipation of these insecticides followed first-order kinetics in fruit with residual half-lives of 4.0 to 4.5 days for thiamethoxam and 2 days for dimethoate. Based on their MRL values of 0.5 and 2.0 mg kg(-1) in mango, pre-harvest intervals of 7 and 11 days, and 6 and 7 days were suggested for thiamethoxam and dimethoate, respectively, after spraying at single and double doses. The theoretical maximum residue contribution (TMRC) values for both the insecticides, calculated for residues corresponding to each sampling date, were found to be below the maximum permissible intake (MPI) values on mango fruit (except for dimethoate double dose up to 3 days); hence, both thiamethoxam and dimethoate could be considered non-hazardous to consumers at the above doses and time intervals. PMID- 26879987 TI - 3-Acylated tetramic and tetronic acids as natural metal binders: myth or reality? AB - Covering: up to 20153-Acylated tetramic and tetronic acids are characterized by a low pKa and are likely to be deprotonated under physiological conditions. In addition, their structure makes them excellent chelators of metallic cations. We will discuss the significance of these chemical properties with regard to the biological properties and mechanisms of action of these compounds, highlighting the importance of considering them as salts or chelates for biological purposes, rather than acids. PMID- 26879988 TI - Pelvic digit: A rare congenital anomaly. PMID- 26879991 TI - Epidemiology of laryngeal carcinoma in Germany, 1998-2011. AB - Constituting 25-30 % of all head and neck cancer cases, laryngeal carcinoma is the most prevalent entity. Major risk factors of laryngeal cancer are smoking and excessive alcohol consumption. This study presents the recent developments in the incidence of laryngeal cancer from 1998 to 2011 in Germany. Laryngeal carcinoma was identified using International Statistical Classification of Diseases and Related Health Problems (ICD10) from German population-based cancer registries. The incidence was provided by the Robert Koch Institute, and the mortality data were derived from German death statistics for further evaluation. Both descriptive and analytical analyses were conducted. From 1998 to 2011, a total of 14,847 laryngeal carcinoma cases were reported, in 13,195 men and 1652 women. Glottic carcinoma represented the main entity, constituting 69 % of male cases and 50 % of female cases. For men, a decline in incidence was observed starting in 2006. The incidence rate for women remained stable for the period of observation. The incidence of laryngeal cancer resembles the development of smoking behaviour in Germany. To maintain the positive trend of the male population and to reduce the incidence in women, it is crucial to continue and to improve the prevention of smoking campaigns in Germany. PMID- 26879992 TI - In response to: Hyaluronic acid fat graft myringoplasty vs. fat patch fat graft myringoplasty. PMID- 26879990 TI - The diagnostic value of narrow band imaging in different oral and oropharyngeal subsites. AB - The diagnostic value of narrow band imaging (NBI) in the "optical biopsy" of leukoplakias (LP) and erythroplakias (EP) in different oral cavity (OC) and oropharyngeal (OP) subsites is still to be defined. We evaluated 128 unbiopsied and untreated OC/OP LP and EP by conventional oral examination (COE), white light (WL) endoscopy, and NBI and categorized them as "suspicious" or "innocuous". All lesions were treated by excisional biopsy. True positives were those considered as "suspicious" and with histopathology ranging from mild dysplasia to invasive carcinoma. Epithelia were classified as follows: type 1, keratinized thick stratified (gingiva, hard palate, dorsal tongue); type 2a, non-keratinized thin stratified (floor of mouth, vestibule, ventral tongue, soft palate, palatine tonsils, base of tongue); type 2b, non-keratinized, very thick stratified (retromolar trigon, lateral tongue, labial and buccal mucosa). Histopathology revealed 32 % benign lesions, 13 % mild to moderate dysplasias, 15 % severe dysplasias/carcinoma in situ, 16 % microinvasive, and 23 % invasive carcinomas. The false positive rates were 32 % at COE, 27 % at WL, and 15 % at NBI. The false negative rates were 49, 22, and 11 %, respectively. Diagnositic performance was higher for NBI compared to COE (p < 0.001) and to WL (p = 0.004). Comparison of the diagnostic value of NBI among different OC/OP subsites did not show statistically significant difference. NBI as an "optical biopsy" tool significantly reduces the rates of false positives and false negatives in diagnosis of OC/OP cancer compared with COE and WL. No statistically significant difference was noted in its diagnostic value among different OC/OP subsites. PMID- 26879989 TI - Heterotrimeric G protein signaling via GIV/Girdin: Breaking the rules of engagement, space, and time. AB - Canonical signal transduction via heterotrimeric G proteins is spatially and temporally restricted, that is, triggered exclusively at the plasma membrane (PM), only by agonist activation of G protein-coupled receptors (GPCRs) via a process that completes within a few hundred milliseconds. Recently, a rapidly emerging paradigm has revealed a non-canonical pathway for activation of heterotrimeric G proteins by the non-receptor guanidine-nucleotide exchange factor (GEF), GIV/Girdin. This pathway has distinctive temporal and spatial features and an unusual profile of receptor engagement: diverse classes of receptors, not just GPCRs can engage with GIV to trigger such activation. Such activation is spatially and temporally unrestricted, that is, can occur both at the PM and on internal membranes discontinuous with the PM, and can continue for prolonged periods of time. Here, we provide the most complete up-to-date review of the molecular mechanisms that govern the unique spatiotemporal aspects of non canonical G protein activation by GIV and the relevance of this new paradigm in health and disease. PMID- 26879993 TI - In response to: The effects of different environmental pH on healing of tympanic membrane: an experimental study. PMID- 26879994 TI - Hearing outcome does not depend on the interval of intratympanic steroid administration in idiopathic sudden sensorineural hearing loss. AB - We studied the effect of intratympanic steroid administration with different intervals on hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The subjects were 197 consecutive patients (197 ears) with ISSNHL (hearing level >=40 dB, interval between onset and treatment <=30 days). They received systemic administration of prednisolone (100 mg followed by tapered doses) combined with intratympanic injection of dexamethasone (4 mg/ml). Intratympanic injection was performed once a week for 4 weeks in 105 patients (long-interval group), or 4 times in 1 week in 92 patients (short-interval group). The hearing outcomes were evaluated at two points of time: 1 week from the start of treatment, and 1-2 months after the completion of treatment when the hearing level reached a plateau. There was no significant difference in the cure rate, marked-recovery rate, recovery rate, hearing gain, hearing level, or percent hearing improvement between the long- and short-interval groups at either point of time. Multiple regression analysis also showed that the final hearing level did not depend on the interval of intratympanic steroid injection. These results indicate that the hearing outcome of ISSNHL does not improve even if the interval of intratympanic injection is shortened. This implies that a lower total number of intratympanic steroid injections may be as effective as the present protocol. PMID- 26879996 TI - Phimosis in male dromedary camels: Clinical findings and changes in the hemogram, nitric oxide metabolites, and testosterone concentrations. AB - The objectives of this study were to elucidate the clinical findings in male dromedary camels with phimosis (PHI, n = 43) and to investigate the association of this syndrome with the hemogram, nitric oxide metabolites (NOMs), and testosterone concentrations. History and signalment were obtained, and a breeding soundness examination was performed. The penis was exteriorized after administration of a pudendal nerve block. Abnormal masses obtained from the prepuce and penis were prepared for histopathology. Blood samples for hemogram assessment were taken from the diseased animals and from 10 healthy control males. Total nitrates/nitrites were determined in sera using the Griess assay. Testosterone was estimated in sera using ELISA. Phimosis associated with detectable pathologic lesions, mainly including ulcerative posthitis and lacerated glans penis, was present in 34 (79.1%) of the 43 cases (PHI-P), whereas the remaining nine (20.9%) of the 43 cases had no noticeable lesions (PHI-N). The PHI-P group showed higher leukocyte counts (P = 0.001), especially neutrophils (P = 0.0001), and greater NOM concentrations (P = 0.002) than the PHI-N and control groups. However, testosterone concentrations did not differ among groups. In conclusion, PHI in the male dromedary camels was mainly associated with ulcerative posthitis and laceration of the glans penis. The presence of pathologic lesions in cases with PHI was associated with leukocytosis, neutrophilia, and high NOM concentrations. PMID- 26879995 TI - Management algorithm for HIV-associated parotid lymphoepithelial cysts. AB - We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (<=18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (>=22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (>=22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade >=3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands. PMID- 26879997 TI - The effect of isosorbide dinitrate on uterine and ovarian blood flow in cycling and early pregnant mares: A pilot study. AB - Poor uterine perfusion has been proposed as a cause of infertility in mares. The objective of this study was to investigate the effect of isosorbide dinitrate (ISDN), a nitric oxide donor, on uterine and ovarian blood flow resistance during diestrus and early pregnancy in mares. Six Trotter mares, aged 7 to 14 years, were examined daily during the first 11 days of three diestrous periods, and five of those mares were also examined during the first 11 days of two pregnancies. Six mares randomly received a placebo, a low dose (30 mg, ISDN30), or a high dose of ISDN (60 mg, ISDN60) through three nonconsecutive cycles. The treatments were administered orally, every 12 hours from Day 1 to 11 of the cycle (Day 0 = ovulation). Five of the 6 mares received a placebo or 60 mg of ISDN orally every 12 hours from Day 1 to 11 of pregnancy. The mares were short cycled on Day 12 of each trial. Transrectal color Doppler was used to determine blood flow resistance semiquantitatively and expressed as pulsatility index. Mean pulsatility index of both uterine arteries combined and of the dominant (ipsilateral to the CL) ovarian artery was lower (treatment effects: P <= 0.01; time effects: P <= 0.002) in mares receiving 30 mg or 60 mg of ISDN compared with placebo-treated mares. Blood flow resistance in the dominant ovarian artery was lower in ISDN-treated pregnant mares than in placebo-treated pregnant and cycling mares (treatment effect: P = 0.04; time effect: P = 0.003). Isosorbide dinitrate increases uterine and ovarian perfusion in cycling mares and ovarian perfusion in early pregnant mares. Further studies are needed to investigate these effects in relation to fertility of the mare. PMID- 26879998 TI - Effects of cilostamide and/or forskolin on the meiotic resumption and development competence of growing ovine oocytes selected by brilliant cresyl blue staining. AB - The relevance of low developmental competence of in vitro-matured oocyte to the incomplete/delayed cytoplasmic maturation, and the heterogeneity of retrieved oocytes is well established in several species. A short phase of prematuration culture was used to allow better oocyte cytoplasmic maturation. The preselection of growing and fully grown oocytes has been proposed to improve developmental competency. This study investigated the effects of phosphodiesterase type 3 specific inhibitor, cilostamide, and adenylate cyclase activator, forskolin, on the resumption of meiosis and developmental competence of growing ovine oocytes selected by brilliant cresyl blue (BCB) staining. Results indicate that cilostamide, forskolin, and their combination significantly (P < 0.05) increased the percentage of growing (BCB-) oocytes maintained at the germinal vesicle stage. However, only forskolin significantly (P < 0.05) increased the yield and quality of blastocysts derived from BCB- oocytes compared with non-BCB-treated oocytes. We conclude that a short prematuration culture with forskolin may improve the in vitro developmental competency of growing oocytes in ovine. PMID- 26879999 TI - Oxidative stress at different stages of two-step semen cryopreservation procedures in dogs. AB - Sperm cryopreservation generates sperm damage and reduced fertilization capacity as a consequence of reactive oxygen species formation. Identifying the critical points of the process will contribute to the development of strategies for oxidative stress prevention. Therefore, the aim of this experiment was to verify the occurrence of oxidative stress during the two-step cryopreservation process in dogs. Six healthy mature dogs were used and submitted to the two-step sperm cryopreservation protocol. The sperm analysis was done at three time points: after refrigeration, after glycerolization, and after thawing by sperm motility, measurement of spontaneous and induced oxidative stress, sperm mitochondrial activity, plasma membrane integrity, flow cytometric evaluation of plasma and acrosome membrane integrity, mitochondrial membrane potential, and sperm chromatin structure assay. There was an increase in free radical production after glycerolization (87.4 +/- 15.5 ng/mL of spontaneous thiobarbituric acid reactive substances (TBARS) after refrigeration and 1226.3 +/- 256.0 ng/mL after glycerolization; P < 0.05), in association with loss of sperm mitochondrial activity. However, frozen-thawed samples had lower sperm motility, lower resistance to oxidative stress (448.7 +/- 23.6 ng/mL of induced TBARS after glycerolization and 609.4 +/- 35.9 ng/mL after thawing; P < 0.05) and increased lipid peroxidation (4815.2 +/- 335.4 ng/mL of spontaneous TBARS after thawing; P < 0.05) as well as increased damage to plasma and acrosomal membranes, compared with refrigeration and glycerolization. In conclusion, the production of free radicals by sperm cells begins during glycerolization. However, sperm oxidative damage intensifies after thawing. Despite intracellular ice formation during cryopreservation, the increased production of reactive oxygen species can be the explanation of the decrease in sperm motility, reduced mitochondrial activity, and sperm plasma membrane and acrosomal damage. PMID- 26880000 TI - The 9-day CIDR-PG protocol: Incorporation of PGF2alpha pretreatment into a long term progestin-based estrus synchronization protocol for postpartum beef cows. AB - A pilot experiment was designed to test the hypothesis that administration of PGF2alpha before progestin treatment would allow for a reduced duration of progestin treatment in a long-term progestin-based estrus synchronization protocol. A modified presynchronization treatment was compared with a standard long-term controlled internal drug release (CIDR) treatment, and treatments were compared on the basis of ovarian follicular dynamics, estrous response rate, synchrony of estrus expression, and pregnancy rates resulting from timed artificial insemination (TAI) in postpartum beef cows. Estrous was synchronized for 85 cows, with cows assigned to one of two treatments based on age, days postpartum, and body condition score. Cows assigned to the 14-day CIDR-PG protocol received a CIDR insert (1.38 g progesterone) on Day 0, CIDR removal on Day 14, and administration of PGF2alpha (25 mg im) on Day 30. Cows assigned to the 9-day CIDR-PG protocol received PGF2alpha concurrent with CIDR insertion on Day 5, PGF2alpha concurrent with CIDR removal on Day 14, and administration of PGF2alpha on Day 30. In both treatments, split-time AI was performed based on estrous response. At 72 hours after PGF2alpha (Day 33), cows having expressed estrus received TAI; cows that failed to express estrus by 72 hours received TAI 24 hours later (96 hours after PGF2alpha on Day 34), with GnRH (100 MUg im) administered to nonestrous cows. Estrus-detection transmitters were used from CIDR removal until AI to determine onset time of estrus expression both after CIDR removal and after PGF2alpha. Ovarian ultrasonography was performed at CIDR removal on Day 14, PGF2alpha on Day 30, and AI on Days 33 or 34. At CIDR removal on Day 14, diameter of the largest follicle present on the ovary was similar between treatments. The proportion of cows expressing estrus after CIDR removal tended to be higher (P = 0.09) among cows assigned to the 9-day CIDR-PG treatment (93%; 40 of 43) than among cows assigned to the 14-day CIDR-PG treatment (81%; 34 of 42). After PGF2alpha, a significantly higher proportion (P = 0.02) of cows expressed estrus after synchronization with the 9-day CIDR-PG treatment (91%; 39 of 43) than the 14-day CIDR-PG treatment (69%; 29 of 42). Consequently, pregnancy rate to TAI tended to be increased (P = 0.09) among the 9-day CIDR-PG treatment (76.7%; 33 of 43) compared with the 14-day CIDR-PG treatment (59.5%; 25 of 42). In summary, a long-term CIDR-based estrous synchronization protocol for postpartum beef cows was enhanced through administration of PGF2alpha at CIDR insertion and CIDR removal. PMID- 26880002 TI - Clandestine abortion causing uterine perforation and bowel infarction in a rural area: a case report and brief review. AB - BACKGROUND: An unsafe abortion is defined as a procedure for terminating an unintended pregnancy carried out either by a person lacking the necessary skills or in an environment that does not conform to minimal medical standards or both. Majority of these unsafe abortions are carried out in rural areas of developing countries, usually by unskilled persons who do not have proper knowledge of the anatomy of reproductive organs and in unhygienic environments thus leading to various complications. CASE PRESENTATION: We discuss the case of a 21 year old female who presented in septic shock after she underwent an unsafe abortion of an 11 weeks pregnancy with uterine wall perforation and bowel injury that required resection. CONCLUSION: Unsafe abortion is an important public health problem which accounts for a significant cause of maternal mortality and morbidity in resource poor countries. A high index of suspicion of clandestine abortion with ensuing complications should prevail when faced with a woman of child bearing age with the triad of vaginal bleeding, amenorrhea and pelvic sepsis. PMID- 26880001 TI - Biocontrol agents promote growth of potato pathogens, depending on environmental conditions. AB - There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain. PMID- 26880003 TI - Long-term radiographic follow-up of bisphosphonate-associated atypical femur fractures. AB - OBJECTIVE: To evaluate the appearance of bisphosphonate-related femur insufficiency fractures on long-term follow-up radiographic studies and to describe the rate of fracture line obscuration and cortical beak healing over time. MATERIALS AND METHODS: In this retrospective study, bisphosphonate-related femur fracture radiographs were reviewed by two radiologists for the presence of a fracture line, callus, and the characteristic cortical beak. Kaplan-Meier curves were used to analyze the time to first indication of healing. Femurs were also subdivided into those who underwent early versus late surgical fixation and those who underwent early versus late discontinuation of bisphosphonate. Clinical data including pain level and medication history were collected. RESULTS: Forty seven femurs with a bisphosphonate-related femur fracture were identified in 28 women. Eighty-five percent took a bisphosphonate for greater than 5 years and 59 % for greater than 10 years. The median time to beak healing was 265 weeks and the median time to fracture line healing was 56 weeks in the 31 femurs with a baseline fracture. No statistically significant difference was identified between surgical fixation and conservative management. CONCLUSIONS: Bisphosphonate related fractures demonstrate notably prolonged healing time on long-term follow up. PMID- 26880004 TI - Prevalence of Hepatitis E Virus (HEV) Antibodies in Mexican Pigs. AB - The hepatitis E virus (HEV) is the causative agent of Hepatitis E, an enterically transmitted disease. HEV infections in pigs and humans have been reported worldwide, but data from Mexico are scarce. In the present study, the prevalence of anti-HEV IgG antibodies was investigated in a quite large number of swine from Mexico by means of an ELISA based on a recombinant open reading frame 2 protein of HEV genotype 3. Serum samples from 683 healthy pigs (1-48 months old), collected during 2010-2013 in 109 herds from 48 municipalities located in 9 states in the centre of the country were assayed. A 30.75 % (210/683) of the sera tested were positive, and they were distributed along all the states included in the study. The prevalence of anti-HEV antibodies varied widely between municipalities and herds, and it was higher in pigs 4-6 months of age. No relationships were detected between seroprevalences and farm characteristics. Forty individual faecal samples were analysed by RT-PCR and all resulted negative. These data indicate that HEV infection is widespread in Mexican pigs; thus, representing a potential zoonotic risk for humans. PMID- 26880005 TI - Influence of Obesity Diagnosis With Organ Dysfunction, Mortality, and Resource Use Among Children Hospitalized With Infection in the United States. AB - BACKGROUND: Sepsis induces inflammation in response to infection and is a major cause of mortality and hospitalization in children. Obesity induces chronic inflammation leading to many clinical manifestations. Our understanding of the impact of obesity on diseases, such as infection and sepsis, is limited. The objective of this study was to evaluate the association of obesity with organ dysfunction, mortality, duration, and charges during among US children hospitalized with infection. METHODS: Retrospective study of hospitalizations in children with infection aged 0 to 20 years, using the 2009 Kids' Inpatient Database. RESULTS: Of 3.4 million hospitalizations, 357 701 were for infection, 5685 of which were reported as obese children. Obese patients had higher rates of organ dysfunction (7.35% vs 5.5%, P < .01), longer hospital stays (4.1 vs 3.5 days, P < .001), and accrued higher charges (US$29 019 vs US$21 200, P < .001). In multivariable analysis, mortality did not differ by obesity status (odds ratio: 0.56, 95% confidence interval: 0.23-1.34), however severity of illness modified the association between obesity status and the other outcomes. CONCLUSIONS: While there was no difference in in-hospital mortality by obesity diagnosis, variation in organ dysfunction, hospital stay, and hospital charges according to obesity status was mediated by illness severity. Findings from this study have significant implications for targeted approaches to mitigate the burden of obesity on infection and sepsis. PMID- 26880006 TI - Does Infection Site Matter? A Systematic Review of Infection Site Mortality in Sepsis. AB - PURPOSE: Sepsis treatment protocols emphasize source control with empiric antibiotics and fluid resuscitation. Previous reviews have examined the impact of infection site and specific pathogens on mortality from sepsis; however, no recent review has addressed the infection site. This review focuses on the impact of infection site on hospital mortality among patients with sepsis. METHODS: The PubMed database was searched for articles from 2001 to 2014. Studies were eligible if they included (1) one or more statistical models with hospital mortality as the outcome and considered infection site for inclusion in the model and (2) adult patients with sepsis, severe sepsis, or septic shock. Data abstracted included stage of sepsis, infection site, and raw and adjusted effect estimates. Nineteen studies were included. Infection sites most studied included respiratory (n = 19), abdominal (n = 19), genitourinary (n = 18), and skin and soft tissue infections (n = 11). Several studies found a statistically significant lower mortality risk for genitourinary infections on hospital mortality when compared to respiratory infections. CONCLUSION: Based on studies included in this review, the impact of infection site in patients with sepsis on hospital mortality could not be reliably estimated. Misclassification among infections and disease states remains a serious possibility in studies on this topic. PMID- 26880007 TI - Hitting the moving target: modelling ontogenetic shifts with stable isotopes reveals the importance of isotopic turnover. AB - Ontogenetic niche shifts are widely prevalent in nature and are important in shaping the structure and dynamics of ecosystems. Stable isotope analysis is a powerful tool to assess these shifts, with delta(15) N providing a measure of trophic level and delta(13) C a measure of energy source. Previous applications of stable isotopes to study ontogenetic niche shifts have not considered the appreciable time lag between diet and consumer tissue associated with isotopic turnover. These time lags introduce significant complexity into field studies of ontogenetic niche shifts. Juvenile Chinook salmon (Oncorhynchus tshawytscha) migrate from freshwater to marine ecosystems and shift their diet from feeding primarily on invertebrates to feeding primarily on fish. This dual ontogenetic habitat and diet shift, in addition to the long time lag associated with isotopic turnover, suggests that there is potential for a disconnect between the prey sources that juvenile salmon are consuming, and the inferred prey sources from stable isotopes. We developed a model that considered ontogenetic niche shifts and time lags associated with isotopic turnover, and compared this 'ontogeny' model to one that considered only isotopic turnover. We used a Bayesian framework to explicitly account for parameter uncertainty. Data showed overwhelming support for the ontogeny model relative to the isotopic turnover model. Estimated variables from best model fits indicate that the ontogeny model predicts a much greater reliance on fish prey than does the stomach content data. Overall, we found that this method of quantifying ontogenetic niche shifts effectively accounted for both isotopic turnover and ontogenetic diet shifts; a finding that could be widely applicable to a variety of systems. PMID- 26880008 TI - Early-life predictors of resilience and related outcomes up to 66 years later in the 6-day sample of the 1947 Scottish mental survey. AB - PURPOSE: Psychological resilience, the ability to manage and quickly recover from stress and trauma, is associated with a range of health and wellbeing outcomes. Resilience is known to relate to personality, self-esteem and positive affect, and may also depend upon childhood experience and stress. In this study, we investigated the role of early-life contributors to resilience and related factors in later life. METHODS: We used data from the 6-day sample of the Scottish mental survey 1947, an initially representative sample of Scottish children born in 1936. They were assessed on a range of factors between the ages of 11 and 27 years, and resilience and other outcomes at 77 years. RESULTS: Higher adolescent dependability unexpectedly predicted lower resilience in older age, as did childhood illnesses, while a count of specific stressors experienced throughout early life significantly predicted higher later-life resilience. We also observed significant cross-sectional correlations between resilience and measures of physical health, mental health, wellbeing and loneliness. Some of the associations between early-life predictors and later-life outcomes were significantly mediated by resilience. CONCLUSIONS: Our results support the hypothesis that stress throughout early life may help to build resilience in later-life, and demonstrate the importance of resilience as a mediator of other influences on health and wellbeing in older age. We suggest that the mechanisms determining how early-life stress leads to higher resilience are worthy of further investigation, and that psychological resilience should be a focus of research and a target for therapeutic interventions aiming to improve older-age health and wellbeing. PMID- 26880009 TI - Information giving challenges and support strategies at the time of a mental health diagnosis: qualitative views from Australian health professionals. AB - PURPOSE: Communication of a mental health diagnosis can be a difficult process and is a poorly understood area of service provision. The aim of this qualitative study was to examine clinicians' perceptions of barriers and helpful strategies to discussing information about a mental health condition. METHOD: Qualitative interviews with 19 Australian clinicians (general practitioners, mental health nurses, psychiatrists, and psychologists) working in several settings (community, hospital inpatient, outpatient, accident and emergency) and locations (urban, suburban and rural) were conducted and analysed thematically. RESULTS: After theme saturation was reached, four primary themes relating to barriers and facilitators to communication at the time of diagnosis were identified in the data. Outside a recognised lack of focus on this area in training, themes included (1) engagement and timing of conversations; (2) stigma and its reduction; (3) perceived and desired knowledge for diagnostic information; and (4) working with distress. The synthesis of themes is demonstrated in a flowchart of suggestions for communicating news of mental health diagnosis that tracks the patient journey in receiving information from initial engagement to follow-up. CONCLUSIONS: Talking with an individual about a mental health diagnosis is a non linear, complex and changeable situation. However, health professionals report using specific strategies to aid this communication process, to meet the specific individual's needs. Strategies such as tailoring to the person's situation, utilising collaborative practice, effective coordination, and addressing stigma may be useful to inform clinician training and support whilst diagnosis remains a key feature of the mental health system in Australia. PMID- 26880010 TI - Pitfalls and solutions in virtual design of nasoalveolar molding plates by using CAD/CAM technology--A preliminary clinical study. AB - PURPOSE: Computer-assisted design and computer-aided manufacturing (CAD/CAM) technology in nasoalveolar molding (NAM) should save time and manpower and reduce family input in cases of cleft lip and palate. MATERIAL AND METHODS: Intraoral casts from 12 infants with complete unilateral cleft lip and palate were taken immediately after birth (T1) and after (T2) NAM treatment, digitalized, and transformed into STL data. The infants were randomized into Group 1 (n = 6) receiving conventional NAM treatment or Group 2 receiving CAD/CAM NAM (n = 6). We analyzed the following variables by using Geomagic software: intersegmental alveolar distance (ISAD); intersegmental lip distance (ISLD); nostril height cleft/noncleft (NHc/nc); nasal width cleft/noncleft (NWn/nc); and columella deviation angle (CDA). RESULTS: In both groups, all variables except NHnc and NWnc were changed significantly between T1 and T2. The analysis of the mean differences of the variables in Group 1 and 2 showed no significant differences, with a comparable incidence of clinical alterations such as skin or mucosal irritations. CONCLUSION: NAM plates can be produced virtually by using CAD/CAM technology. The CAD/CAM NAM results show no significant differences from the conventional technique. We present our clinically usable virtual CAD/CAM workflow for producing a basic NAM plate. PMID- 26880011 TI - Utility of 18F-fluorodeoxy glucose and 18F-sodium fluoride positron emission tomography/computed tomography in the diagnosis of medication-related osteonecrosis of the jaw: A preclinical study in a rat model. AB - PURPOSE: The aim of this study was to determine the clinical utility of positron emission tomography/computed tomography (PET/CT) using 18F-FDG and 18F-NaF for the diagnosis of osteonecrosis of the jaw (ONJ), by observing characteristics in rat models treated with zoledronic acid (ZA) and/or dexamethasone (DX) followed by tooth extraction. MATERIAL AND METHODS: A total of 48 rats were divided randomly into four groups: Group 1, rats treated with ZA and DX; Group 2, rats treated with ZA; Group 3, rats treated with DX; and Group 4, rats treated with vehicle as normal controls. They underwent examinations with both 18F-FDG and 18F NaF PET/CT at 4 weeks prior to tooth extraction (baseline) and 4 weeks after tooth extraction. Rats were then sacrificed to evaluate the histological incidence and characteristics of ONJ. Histological and radiological characteristics of all groups were compared to assess the effects of medication and tooth extraction. RESULTS: Baseline PET/CT studies using 18F-FDG and 18F-NaF showed no difference in uptake among the groups. However, 18F-FDG PET/CT performed at 4 weeks after tooth extraction showed increased glucose metabolism at the extraction site in both the ZA/DX and the ZA-only groups compared with that in the vehicle-treated group, in accordance with the higher incidence of histological ONJ (p < 0.05, respectively). 18F-NaF PET/CT performed at 4 weeks after tooth extraction showed decreased bone uptake in the extraction site in the ZA/DX, ZA, and DX groups versus the vehicle group (all p < 0.05), but this was not correlated with the incidence of histological ONJ. The incidence of ONJ was highest in the ZA/DX group (66.7%), followed by the ZA group, both of which were significantly higher than in the DX and vehicle groups (both p < 0.05). CONCLUSIONS: 18F-FDG PET/CT as an inflammatory marker appeared to be a more appropriate imaging modality than 18F-NaF PET/CT in diagnosing ONJ in a rat model including a ZA/DX group. However, the decreased bone remodeling tendency highlighted by 18F-NaF PET/CT may be an indicator of a possible risk of ONJ before the onset of clinical signs and symptoms. PMID- 26880012 TI - Three-dimensional analysis of maxillary stability after Le Fort I osteotomy using hydroxyapatite/poly-L-lactide plate. AB - PURPOSE: To evaluate three-dimensional change in maxillary position using biodegradable plates. MATERIAL AND METHODS: A total of 53 patients who underwent orthognathic surgery using biodegradable plates were analyzed retrospectively. The position of maxilla was measured three-dimensionally using cone beam computed tomography data at preoperative (T0), 1-month postoperative (T1), and 1-year postoperative (T2) time points. Changes in the maxilla 1 year after the operation (T2-T1) were analyzed to demonstrate postoperative stability. The correlation between postoperative relapse (T2-T1) and surgical movement (T1-T0) of the maxilla was investigated. RESULTS: At 1-year postoperatively, no significant changes in maxillary position were noted in the antero-posterior and transverse dimensions. The anterior maxillary position in the vertical dimension also showed no significant changes, but the posterior maxillary position (posterior nasal spine, greater palatine foramen) showed a 0- to 2.98-mm relapse at 1-year postoperatively. The posterior maxilla tended to relapse inferiorly when the amount of surgical upward movement was greater than 3-3.5 mm and to relapse superiorly when the amount of surgical upward movement was less than 3-3.5 mm. For all patients, no postoperative complications in the osteofixated maxilla were observed during the follow-up period. CONCLUSION: Maxilla fixed with biodegradable plates was stable in the antero-posterior and transverse and the vertical (anterior maxilla) dimensions. Posterior maxillary vertical relapse was clinically acceptable, but relapse patterns that relate to the amount of surgical upward movement should be considered for surgical treatment planning. PMID- 26880013 TI - Eyelid fat grafting: Indications, operative technique and complications; a systematic review. AB - INTRODUCTION: Many recent studies concerning autologous fat grafting in the eyelids have been published, mostly consisting of case reports and retrospective case series. However, no study on the overall complication or satisfaction rate associated with the various grafting techniques exists. We performed a comprehensive literature review to determine the outcomes and complications of eyelid fat grafting, as well as patient satisfaction. METHODS: A systematic review of the literature using the PRISMA criteria was conducted. This protocol was registered at the Prospective Register of Systematic Reviews at the National Institute for Health Research. RESULTS: Sixteen studies, representing 1,159 patients and published between June 2004 and December 2014, were included. Satisfactory results, judged by clinical examination, were observed in all studies. Few postoperative complications were reported. CONCLUSIONS: We demonstrated that the procedures were easy to perform, and achieved satisfactory and sustainable results with few complications in both reconstructive and cosmetic surgery. However, a wide disparity exists in the various fat harvesting, fat purification, and reinjection techniques. Further studies are required to assess the long-term outcomes. Our conclusions should be accepted cautiously due to the small number of articles and the lack of evidence in published studies. PMID- 26880014 TI - Nasofacial angle and nasal prominence: A quantitative investigation of idealized and normative values. AB - PURPOSE: A quantitative evaluation of the influence of the nasofacial angle on perceived attractiveness and threshold values of desire for rhinoplasty. MATERIAL AND METHODS: The nasofacial angle of an idealized silhouette male Caucasian/white profile image was altered incrementally between 21 degrees and 48 degrees . Images were rated on a Likert scale by pretreatment patients (n = 75), laypersons (n = 75), and clinicians (n = 35). RESULTS: A nasofacial angle of approximately 30 degrees was deemed to be ideal, with a range of 27 degrees -36 degrees deemed acceptable. Angles above or below this range were perceived as unattractive. Angles outside the range of 21 degrees -42 degrees were deemed very unattractive. Excessive nasal prominence (nasofrontal angle of 48 degrees ) was deemed the least attractive. In terms of threshold values of desire for surgery, for all groups a threshold value of >=39 degrees and <=24 degrees indicated a preference for surgery, with clinicians least likely to suggest surgery. The patient group assessments demonstrated the greatest variability, stressing the importance of using patients as observers, as well as laypersons and clinicians, in facial attractiveness research. CONCLUSIONS: It is recommended that in rhinoplasty planning, the range of normal variability of the nasofrontal angle, in terms of observer acceptance, is taken into account, as well as threshold values of desire for surgery. PMID- 26880015 TI - Discopexy using resorbable pins in temporomandibular joint arthroscopy: Clinical and magnetic resonance imaging medium-term results. AB - PURPOSE: To describe the use of resorbable pins for disc fixation in a series of patients and their medium-term outcomes. MATERIALS AND METHODS: A study was conducted in 26 patients who underwent operative arthroscopic surgery and discopexy using resorbable pins. All patients were refractory to conservative treatment and presented, in at least one joint, anterior disc displacement without reduction on magnetic resonance imaging (MRI). Pre- and postoperative evaluation parameters were disc position on MRI, maximal interincisal opening, lateral movements, joint pain, and articular locking and clicking. RESULTS: The technique was performed in 34 joints, and 47 pins were inserted. Mouth opening increased significantly, from a mean of 31.24 mm preoperatively to 39.57 mm 1 year postoperatively (p < 0.05). Patients reported a decrease in pain, obtaining values on a visual analogue scale (1-100) of less than 20 after 1 year postsurgery (mean improvement 47.9 points, p < 0.05). Analyzing 1-year MRI findings, in 65% of joints the discs were repositioned and in 20% of joints discs were in a more posterior position. CONCLUSIONS: The use of resorbable pins is a useful technique for disc fixation and shows medium-term improvement in clinical parameters and mandibular function. However, further studies are needed to evaluate a longer follow-up, joint morphologic changes, and disc stability on imaging. PMID- 26880016 TI - The Effect of Hydrophile Topology in RAFT-Mediated Polymerization-Induced Self Assembly. AB - Polymerization-induced self-assembly (PISA) was employed to compare the self assembly of different amphiphilic block copolymers. They were obtained by emulsion polymerization of styrene in water using hydrophilic poly(N acryloylmorpholine) (PNAM)-based macromolecular RAFT agents with different structures. An average of three poly (ethylene glycol acrylate) (PEGA) units were introduced either at the beginning, statistically, or at the end of a PNAM backbone, resulting in formation of nanometric vesicles and spheres from the two former macroRAFT architectures, and large vesicles from the latter. Compared to the spheres obtained with a pure PNAM macroRAFT agent, composite macroRAFT architectures promoted a dramatic morphological change. The change was induced by the presence of PEGA hydrophilic side-chains close to the hydrophobic polystyrene segment. PMID- 26880017 TI - Margins in breast conserving surgery: A practice-changing process. AB - Margins in breast conserving surgery (BCS) have been a long standing subject debate. This largely arises from the absence of a consensus on what constitutes an adequate margin width, resulting in re-excision rates of 25-40% for close or positive margins and its consequent impact upon cosmesis, economic costs, patient dissatisfaction and lack of bearing on survival. Accepting that the increased risk of local recurrences (LR) has its influence on survival, the decrease in LR in BCS in the last decade have been motivated by better surgical techniques for assessing negative margins, use of targeted therapies and in general with the multimodal treatment in the management of breast cancer patients. Since the publication of the consensus guidelines on margins there has evolved a trend of changing attitudes towards re-excision. Surgeons are considering margins in the context of all factors including not only patient and tumor characteristics but also the regional and systemic treatment the patient is receiving. PMID- 26880018 TI - A homozygous nonsense variant in IFT52 is associated with a human skeletal ciliopathy. AB - Intraflagellar transport (IFT) is vital for the functioning of primary cilia. Defects in several components of IFT complexes cause a spectrum of ciliopathies with variable involvement of skeleton, brain, eyes, ectoderm and kidneys. We examined a child from a consanguineous family who had short stature, narrow thorax, short hands and feet, postaxial polydactyly of hands, pigmentary retinopathy, small teeth and skeletal dysplasia. The clinical phenotype of the child shows significant overlap with cranioectodermal dysplasia type I (Sensenbrenner syndrome). Whole-exome sequencing revealed a homozygous nonsense variant p.R142* in IFT52 encoding an IFT-B core complex protein as the probable cause of her condition. This is the first report of a human disease associated with IFT52. PMID- 26880019 TI - Evidence for No Significant Impact of Mullerian Anomalies on Reproductive Outcomes of Twin Pregnancy in Korean Women. AB - The present article aimed to evaluate the impact of congenital Mullerian anomalies (MA) on twin pregnancy after 24 gestational weeks in Korean women. All records of twin pregnancies in a large maternity hospital in Korea between January 2005 and July 2013 were analyzed. Patients with monochorionic monoamniotic (MCMA) twins, non-Korean patients, patients with twins delivered prior to 24 gestational weeks, and patients with miscarriage of one fetus or intrauterine fetal death (IUFD) before 24 gestational weeks were excluded from data analysis. In total, 1,422 women with twin pregnancy were eligible for data analysis, including 17 (1.2%) who had a known congenital MA (septate uterus, bicornuate uterus, arcuate uterus, and unicornuate uterus). Except for the mode of conception, baseline demographics were similar between women with MA and those without MA. No significant differences were found in pregnancy outcomes of gestational age at delivery (p = .86), birth weight of smaller and larger twins (p = .54 and p = .65), and number of twins with birth weight <5th percentile for gestational age (p = .43).The rates of obstetrical complications such as pre eclampsia, gestational diabetes mellitus (GDM), placenta previa, cerclage, IUFD, and postpartum hemorrhage were not significantly different between the two groups either. We concluded that the presence of congenital MA may not increase obstetrical risks in outcomes of pregnancy of twins delivered after 24 gestational weeks. PMID- 26880021 TI - High cholesterol diet is not linked to increased heart risk, study shows. PMID- 26880020 TI - Nuclear ferritin mediated regulation of JNK signaling in corneal epithelial cells. AB - Corneal epithelial (CE) cells are exposed to environmental insults (e.g., UV irradiation), yet they suffer little damage. Our previous studies suggest that chicken CE cells have a novel form of protection involving having ferritin in a nuclear location where it can bind to DNA and sequester free iron. Here we describe another potential nuclear ferritin-mediated protective mechanism: the down-regulation of the JNK signaling pathway. The JNK pathway has been shown by others to promote apoptosis in response to cell damage and also to be activated in CE cell lines following exposure to UV radiation. Here we show in COS7 reporter cell lines that the expression of ferritin in a nuclear localization significantly down-regulates the JNK pathway (p = 5.7 * 10(-6)), but has no effect on the NFkB or the Erk pathways. In organ cultures of embryonic chicken corneas, we observed that inhibiting the synthesis of nuclear ferritin in CE cells, using the iron-chelating molecule deferoxamine, led to an increase in JNK signaling, as measured by phospho-JNK levels compared to CE cells with nuclear ferritin. Furthermore, the chemical inhibition of the JNK pathway using the molecule AS601245 decreased the production of nuclear ferritin. Taken together, these observations suggest that in CE cells a feedback-loop exists in which JNK signaling increases the production of nuclear ferritin and, in turn, nuclear ferritin decreases the activity of the JNK signaling pathway. PMID- 26880022 TI - Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson's disease. AB - Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidance molecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidance molecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidance molecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl glycine as biomarkers for oxidative stress exposure decreased, repulsive guidance molecule A and levodopa rose. Repulsive guidance molecule A remained unchanged in levodopa naive patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidance molecule A rise may inhibit physiologic mechanisms for neuronal survival. PMID- 26880024 TI - Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight mass spectrometry assay solves misidentification of rapidly growing mycobacteria. PMID- 26880023 TI - Associations between prenatal mercury exposure and early child development in the ALSPAC study. AB - INTRODUCTION: There is evidence that high levels of mercury exposure to the pregnant woman can result in damage to the brain of the developing fetus. However there is uncertainty as to whether lower levels of the metal have adverse effects on the development of the infant and whether components of fish consumption and/or the selenium status of the woman is protective. METHODS: In this study we analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n=2875-3264) to determine whether levels of total blood mercury of pregnant women collected in the first half of pregnancy are associated with the development of the offspring at ages 6, 18, 30 and 42 months. The developmental measures used maternal self-reported scales for individual types of development (fine and gross motor, social and communication skills) and total scores. Multiple and logistic regression analyses treated the outcomes both as continuous and as suboptimal (the lowest 15th centile). The statistical analyses first examined the association of prenatal mercury exposure with these developmental endpoints and then adjusted each for a number of social and maternal lifestyle factors; finally this model was adjusted for the blood selenium level. RESULTS: Total maternal prenatal blood mercury and selenium ranged from 0.17 to 12.76 and 17.0 to 324MUg/L respectively. We found no evidence to suggest that prenatal levels of maternal blood mercury were associated with adverse development of the child, even when the mother had consumed no fish during pregnancy. In general, the higher the mercury level the more advanced the development of the child within the range of exposure studied. For example, the fully adjusted effect sizes for total development at 6 and 42 months were +0.51 [95%CI +0.05, +1.00] and +0.43 [95%CI +0.08, +0.78] points per SD of mercury. For the risk of suboptimal development the ORs at these ages were 0.90 [95%CI 0.80, 1.02] and 0.88 [95%CI 0.77, 1.02]. In regard to the associations between blood mercury and child development there were no differences between the mothers who ate fish and those who did not, thus implying that the benefits were not solely due to the beneficial nutrients in fish. CONCLUSIONS: We found no evidence of adverse associations between maternal prenatal blood mercury and child development between 6 and 42 months of age. The significant associations that were present were all in the beneficial direction. PMID- 26880026 TI - Central motor conduction time as prodromal biomarker in spinocerebellar ataxia type 2. PMID- 26880025 TI - Safety and Feasibility of Laparoscopic Nephrectomy for Big Tumors (>= 10 cm): A Retrospective Multicentric Study. AB - OBJECTIVE: Evaluate the feasibility of laparoscopic nephrectomy for big tumors. MATERIAL AND METHODS: Data from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, pre- and postoperative parameters, and renal function before and after surgery were analyzed. RESULTS: Mean age and body mass index were 61 years and 27.8 kg/m(2), respectively. Males represented 63.8% of patients, and 54.4% presented symptoms at diagnosis. Median tumor size was 11 cm, and 75% of the cases were performed by expert surgeons. Median operative time and blood loss were 180 minutes and 200 mL respectively. Conversion to open surgery was necessary in 20.7% of cases. Intraoperative complications related to massive hemorrhage occurred in 16.4% of patients, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intraoperative complications, age, and blood loss were predictive factors of conversion to open surgery. Positive surgical margins occurred in 6 patients (5.2%). None of them presented a local recurrence. Predictive factors of recurrence or progression were lymph node invasion, metastases, and Furhman grade. CONCLUSION: Laparoscopic nephrectomy for tumors > 10 cm can be performed safely. Complication rate and positive surgical margins are similar to open surgery. In experienced hands, the benefit of a mini invasive surgery remains evident. PMID- 26880027 TI - Ab initio molecular dynamics simulation of the effects of stacking faults on the radiation response of 3C-SiC. AB - In this study, an ab initio molecular dynamics method is employed to investigate how the existence of stacking faults (SFs) influences the response of SiC to low energy irradiation. It reveals that the C and Si atoms around the SFs are generally more difficult to be displaced than those in unfaulted SiC, and the corresponding threshold displacement energies for them are generally larger, indicative of enhanced radiation tolerance caused by the introduction of SFs, which agrees well with the recent experiment. As compared with the unfaulted state, more localized point defects are generated in faulted SiC. Also, the efficiency of damage production for Si recoils is generally higher than that of C recoils. The calculated potential energy increases for defect generation in SiC with intrinsic and extrinsic SFs are found to be higher than those in unfaulted SiC, due to the stronger screen-Coulomb interaction between the PKA and its neighbors. The presented results provide a fundamental insight into the underlying mechanism of displacement events in faulted SiC and will help to advance the understanding of the radiation response of SiC with and without SFs. PMID- 26880029 TI - Gender Differences in the Incidence of Depression Among Immigrants and Natives in Aragon, Spain. AB - Knowledge of depression among immigrants within Spanish primary care is limited. This database study investigates the incidence of depressive disorders among immigrants and natives within primary care in Aragon (Spain). Participants were patients registered in an electronic record register, aged above 20 years diagnosed with depression. Incidence of depression was calculated and compared per continent of origin, gender and age with the Mann-Whitney U test and the Kruskal-Wallis test. The population consisted of 11,088 patients with depression of whom 93.0 % natives and 7.0 % immigrants. Incidence of depression amongst male immigrants was lower than amongst male natives (OR 0.80). Eastern European males showed the lowest incidence 4.1 (3.5-5.3). The gender difference in incidence was larger in immigrants than in natives (OR 3.4 vs. 2.7). Due to male immigrants the incidence of depression within primary care is lower among immigrants. Equal care should be provided to patients of both genders and all origin. PMID- 26880028 TI - The Klotho gene G-395A polymorphism and metabolic syndrome in very elderly people. AB - BACKGROUND: To investigate the possible association of the Klotho G-395A polymorphism and metabolic syndrome (MetS) among a population of Chinese nonagenarians and centenarians. METHODS: Subjects were from the Project of Longevity and Aging in Dujiangyan (PLAD). The genotyping of G-395A (rs1207568) in the promoter region of the Klotho gene was performed using the TaqMan allelic discrimination assay. MetS was diagnosed according to the International Diabetes Federation criteria. RESULTS: We included 695 subjects aged 93.5 +/- 3.2 years. G and A allele frequencies were 0.852 and 0.148, respectively. In the whole population, the frequency of MetS was 10.8% and 5.9% in the GG and GA + AA genotype group, respectively (p = 0.004). The -395A allele carriers had significantly lower risk of MetS in the whole population (odd ratio [OR] 0.50, 95% confidential interval [CI] 0.25 to 0.98) and in women (OR 0.51, 95% CI 0.24 to 0.97), but not in men (OR 0.42, 95% CI 0.05 to 3.85). In the whole population and women, the relationship between the Klotho G-395A SNP and MetS might due to its influence on high blood pressure (OR 0.48, 95% CI 0.34 to 0.67; OR 0.47, 95% CI 0.31 to 0.71, respectively) and hypertriglyceridemia (OR 0.66, 95% CI 0.39 to 0.95; OR 0.54, 95% CI 0.31 to 0.98, respectively). In men, this relationship might due to its influence on high blood pressure (OR 0.47, 95% CI 0.25 to 0.90) and low HDL-C (OR 0.69, 95% CI 0.27 to 0.93). CONCLUSIONS: The -395A allele carriers of the Klotho gene were correlated with lower risk of MetS among Chinese nonagenarians and centenarians, especially in women. PMID- 26880030 TI - Undocumented Immigrant Women in Spain: A Scoping Review on Access to and Utilization of Health and Social Services. AB - This scoping review summarizes and analyzes relevant studies related to the evidence published on undocumented immigrant women's access to and utilization of health and social services in Spain. Scientific literature was identified by entering search terms in seven electronic databases which combined retrieved health sciences peer-reviewed articles (Pubmed, Embase, CINAHL Plus and Scopus) and grey literature databases (Europa OpenGrey, DART-Europe and Google Scholar) published between 2004 and 2014 and written in Spanish or in English presenting data about Spain. Those that fulfill the inclusion criteria were selected after a blind peer reviewed process when pertinence and quality was debated. A total of 16 publications were included, the main topics being socio-cultural differences in the access and utilization of social and health services and barriers faced by immigrant women. None of the studies focused exclusively on undocumented women, hence further research is needed in this area. PMID- 26880031 TI - NPR2 is involved in FSH-mediated mouse oocyte meiotic resumption. AB - BACKGROUND: Previous studies have reported that follicle-stimulating hormone (FSH) is often added to culture media to induce oocyte meiotic resumption and maturation and to improve subsequent embryonic development during in vitro maturation (IVM). However, the underlying mechanisms remain unclear. METHODS: Cumulus-oocyte complexes (COCs) were collected from ovaries 46-48 h after the female mice were intraperitoneally injected with 8 IU equine chorionic gonadotropin (eCG) and then the COCs were cultured in different medium. qRT-PCR analysis was used to assess mRNA expression of EGF-like factors and natriuretic peptide receptor 2 (NPR2). Western Blot analysis was used to assess phosphorylation of mitogen-activated protein kinase 3/1 (MAPK3/1). The oocytes were morphologically assessed for meiotic resumption. RESULTS: FSH stimulated the expression of EGF-like factors, the activation of MAPK3/1, a decrease in NPR2 mRNA and oocyte meiotic resumption. Moreover, the FSH-induced decrease in NPR2 and oocyte meiotic resumption occurred via the MAPK3/1 singling pathway, which was activated by the epidermal growth factor receptor (EGFR) pathway. CONCLUSIONS: NPR2 is involved in FSH-mediated oocyte meiotic resumption, and this process is associated with the EGFR and MAPK3/1 signaling pathways. PMID- 26880033 TI - The anterior and posterior pedunculopontine tegmental nucleus are involved in behavior and neuronal activity of the cuneiform and entopeduncular nuclei. AB - Loss of cholinergic neurons in the mesencephalic locomotor region, comprising the pedunculopontine nucleus (PPN) and the cuneiform nucleus (CnF), is related to gait disturbances in late stage Parkinson's disease (PD). We investigate the effect of anterior or posterior cholinergic lesions of the PPN on gait-related motor behavior, and on neuronal network activity of the PPN area and basal ganglia (BG) motor loop in rats. Anterior PPN lesions, posterior PPN lesions or sham lesions were induced by stereotaxic microinjection of the cholinergic toxin AF64-A or vehicle in male Sprague-Dawley rats. First, locomotor activity (open field), postural disturbances (Rotarod) and gait asymmetry (treadmill test) were assessed. Thereafter, single-unit and oscillatory activities were measured in the non-lesioned area of the PPN, the CnF and the entopeduncular nucleus (EPN), the BG output region, with microelectrodes under urethane anesthesia. Additionally, ECoG was recorded in the motor cortex. Injection of AF64-A into the anterior and posterior PPN decreased cholinergic cell counts as compared to naive controls (P<0.001) but also destroyed non-cholinergic cells. Only anterior PPN lesions decreased the front limb swing time of gait in the treadmill test, while not affecting other gait-related parameters tested. Main electrophysiological findings were that anterior PPN lesions increased the firing activity in the CnF (P<0.001). Further, lesions of either PPN region decreased the coherence of alpha (8-12 Hz) band between CnF and motor cortex (MCx), and increased the beta (12-30 Hz) oscillatory synchronization between EPN and the MCx. Lesions of the PPN in rats had complex effects on oscillatory neuronal activity of the CnF and the BG network, which may contribute to the understanding of the pathophysiology of gait disturbance in PD. PMID- 26880032 TI - WBSMDA: Within and Between Score for MiRNA-Disease Association prediction. AB - Increasing evidences have indicated that microRNAs (miRNAs) are functionally associated with the development and progression of various complex human diseases. However, the roles of miRNAs in multiple biological processes or various diseases and their underlying molecular mechanisms still have not been fully understood yet. Predicting potential miRNA-disease associations by integrating various heterogeneous biological datasets is of great significance to the biomedical research. Computational methods could obtain potential miRNA disease associations in a short time, which significantly reduce the experimental time and cost. Considering the limitations in previous computational methods, we developed the model of Within and Between Score for MiRNA-Disease Association prediction (WBSMDA) to predict potential miRNAs associated with various complex diseases. WBSMDA could be applied to the diseases without any known related miRNAs. The AUC of 0.8031 based on Leave-one-out cross validation has demonstrated its reliable performance. WBSMDA was further applied to Colon Neoplasms, Prostate Neoplasms, and Lymphoma for the identification of their potential related miRNAs. As a result, 90%, 84%, and 80% of predicted miRNA disease pairs in the top 50 prediction list for these three diseases have been confirmed by recent experimental literatures, respectively. It is anticipated that WBSMDA would be a useful resource for potential miRNA-disease association identification. PMID- 26880034 TI - Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants. AB - BACKGROUND: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a class of antiretroviral compounds that bind in an allosteric binding pocket in HIV-1 RT, located about 10 A from the polymerase active site. Binding of an NNRTI causes structural changes that perturb the alignment of the primer terminus and polymerase active site, preventing viral DNA synthesis. Rilpivirine (RPV) is the most recent NNRTI approved by the FDA, but like all other HIV-1 drugs, suboptimal treatment can lead to the development of resistance. To generate better compounds that could be added to the current HIV-1 drug armamentarium, we have developed several RPV analogs to combat viral variants that are resistant to the available NNRTIs. RESULTS: Using a single-round infection assay, we identified several RPV analogs that potently inhibited a broad panel of NNRTI resistant mutants. Additionally, we determined that several resistant mutants selected by either RPV or Doravirine (DOR) caused only a small increase in susceptibility to the most promising RPV analogs. CONCLUSIONS: The antiviral data suggested that there are RPV analogs that could be candidates for further development as NNRTIs, and one of the most promising compounds was modeled in the NNRTI binding pocket. This model can be used to explain why this compound is broadly effective against the panel of NNRTI resistance mutants. PMID- 26880035 TI - Current practices in corrosion, surface characterization, and nickel leach testing of cardiovascular metallic implants. AB - In an effort to better understand current test practices and improve nonclinical testing of cardiovascular metallic implants, the Food and Drug Administration (FDA) held a public workshop on Cardiovascular Metallic Implants: corrosion, surface characterization, and nickel leaching. The following topics were discussed: (1) methods used for corrosion assessments, surface characterization techniques, and nickel leach testing of metallic cardiovascular implant devices, (2) the limitations of each of these in vitro tests in predicting in vivo performance, (3) the need, utility, and circumstances when each test should be considered, and (4) the potential testing paradigms, including acceptance criteria for each test. In addition to the above topics, best practices for these various tests were discussed, and knowledge gaps were identified. Prior to the workshop, discussants had the option to provide feedback and information on issues relating to each of the topics via a voluntary preworkshop assignment. During the workshop, the pooled responses were presented and a panel of experts discussed the results. This article summarizes the proceedings of this workshop and background information provided by workshop participants. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. J Biomed Mater Res Part B: Appl Biomater, 105B: 1330-1341, 2017. PMID- 26880036 TI - Narrative review of women's health in Iran: challenges and successes. AB - BACKGROUND: In each society, the health of women in different periods may be endangered by an unequal distribution of resources, facilities, and gender prejudices. The present study evaluated the time trend of Iranian women's health between 1990 and 2013. METHODS: This narrative review includes an integration and descriptive summary of the existing evidence on trends and criteria of different aspects of women's health from social determinant point of view. The evidence was drawn from peer-reviewed, cross-national or large-scale studies, official sources of the Ministry of Health, reviews, and online scientific databases published between 1990 and 2013. RESULTS: The average life expectancy of Iranian women has increased from 44.15 years in 1960 to 75.75 years in 2012; in most deprived provinces of Iran, however, this criterion is about 67.3 years, and in the capital it is 75.8 years. In 2011, 43.37 % of DALYS, 36.21 % of YLL, and 1.92 % of YLD were dedicated to women; these figures were 3.63 % lower than they were in 2003. Although a significant reduction has occurred in maternal mortality rate, which dropped from 83 to 23 per 100,000 between 1990 and 2013, there is no equal distribution in maternal mortality across the country as manifested by the unfavorable conditions of border provinces (SD = 19.2). The prevalence of HIV/AIDS is an alarming health problem among Iranian females, increasing approximately 546 % between 2007 and 2015. As for mental health, depression in women was ranked first among diseases in 2011 compared to a second place ranking in 2003. As regards social health, the delinquency of women has increased in recent years compared to men with women committing more crimes related to drugs and actions against virtue. The annual report of the United Nations for the gender gap index in 2013 ranked Iran as 130 among 136 countries (from 0.622 in 2000 to 0.584 in 2013). CONCLUSION: Generally, over the last three decades, the health indices of Iranian women have grown in aspects of physical, mental, and social health. Remarkable differences can be seen among female health indices based on geographic location and in comparison with men. To promote an improved health status for Iranian women, the root causes of the discrepancies must be identified and a comprehensive national plan must be established. PMID- 26880037 TI - Men's harassment behavior in online video games: Personality traits and game factors. AB - Online video games afford co-play and social interaction, often anonymous, among players from around the world. As predicted by the social identity model of deindividuation effects, undesirable behavior is not uncommon in online gaming environments, and online harassment has become a pervasive issue in the gaming community. In this study, we sought to determine what personality traits and game related variables predicted two types of online aggression in video games: general harassment (e.g., skill-based taunting, insulting others' intelligence) and sexual harassment (e.g., sexist comments, rape threats). Men who play online video games (N = 425) participated in an anonymous online survey. Social dominance orientation and hostile sexism predicted higher levels of both sexual harassment and general harassment in online games. Game involvement and hours of weekly gameplay were additional predictors of general harassment. We discuss implications of online social aggression and online sexual harassment for online gaming. We also apply our findings to the broader understanding of online harassment, cyberaggression, cyberbullying, and other forms of online hostility in computer-mediated communication contexts. Aggr. Behav. 42:513-521, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26880038 TI - Macrophages: sentinels and regulators of the immune system. AB - The important role of macrophages in host defense against a variety of pathogens has long been recognized and has been documented and reviewed in numerous publications. Recently, it has become clear that tissue macrophages are not entirely derived from monocytes, as has been assumed for a long time, but rather show an ontogenetic dichotomy in most tissues: while part of the tissue macrophages are derived from monocytes, a major subset is prenatally seeded from the yolk sac. The latter subset shows a remarkable longevity and is maintained by self-renewal in the adult animal. This paradigm shift poses interesting questions: are these two macrophage subsets functionally equivalent cells that are recruited into the tissue at different development stages, or are both macrophage subsets discrete cell types with distinct functions, which have to exist side by side? Is the functional specialization that can be observed in most macrophages due to their lineage or due to their anatomical niche? This review will give an overview about what we know of macrophage ontogeny and will discuss the influence of the macrophage lineage and location on their functional specialization. PMID- 26880039 TI - Copper-Catalyzed Insertion into Heteroatom-Hydrogen Bonds with Trifluorodiazoalkanes. AB - Copper-catalyzed Si-H, B-H, P-H, S-H, and N-H insertion reactions of 2,2,2 trifluoro-1-diazoethane and 1-aryl 2,2,2-trifluorodiazoethanes generated a large number of new fluorine-containing chemical entities for medicinal chemists. With selected Si-H and B-H insertion reactions, we demonstrate successful extension to asymmetric catalysis. PMID- 26880040 TI - Low Beclin-1 expression predicts improved overall survival in patients treated with immunomodulatory drugs for multiple myeloma and identifies autophagy inhibition as a promising potentially druggable new therapeutic target: an analysis from The Austrian Myeloma Registry (AMR). AB - Beclin-1 is a key regulator of autophagy and has been suggested to be involved in the development of drug resistance in multiple myeloma (MM). We analyzed the expression of Beclin-1 in a retrospective cohort of 70 MMs. Beclin-1 expression did not influence overall survival (OS) and progression-free survival (PFS) in patients with therapy-naive MM. In patients treated with immunomodulatory drugs (IMiDs) lack of or low Beclin-1 expression resulted in a significantly improved OS and PFS compared to those treated with bortezomib or nonnovel agents. Beclin-1 expression was more frequently detected in relapsed MM than in therapy-naive MM probably being a hallmark of tumor progression and therapy resistance. If validated prospectively, Beclin-1 expression might identify patients prone to profit above average from IMiDs and enable a more rational allocation of antimyeloma therapies. Furthermore, the inhibition of autophagy could be a new promising target to improve response to treatment in the relapsed/refractory setting. PMID- 26880041 TI - Athermal domain-wall creep near a ferroelectric quantum critical point. AB - Ferroelectric domain walls are typically stationary because of the presence of a pinning potential. Nevertheless, thermally activated, irreversible creep motion can occur under a moderate electric field, thereby underlying rewritable and non volatile memory applications. Conversely, as the temperature decreases, the occurrence of creep motion becomes less likely and eventually impossible under realistic electric-field magnitudes. Here we show that such frozen ferroelectric domain walls recover their mobility under the influence of quantum fluctuations. Nonlinear permittivity and polarization-retention measurements of an organic charge-transfer complex reveal that ferroelectric domain-wall creep occurs via an athermal process when the system is tuned close to a pressure-driven ferroelectric quantum critical point. Despite the heavy masses of material building blocks such as molecules, the estimated effective mass of the domain wall is comparable to the proton mass, indicating the realization of a ferroelectric domain wall with a quantum-particle nature near the quantum critical point. PMID- 26880042 TI - Mitigation of Coral Reef Warming Across the Central Pacific by the Equatorial Undercurrent: A Past and Future Divide. AB - Global climate models (GCMs) predict enhanced warming and nutrient decline across the central tropical Pacific as trade winds weaken with global warming. Concurrent changes in circulation, however, have potential to mitigate these effects for equatorial islands. The implications for densely populated island nations, whose livelihoods depend on ecosystem services, are significant. A unique suite of in situ measurements coupled with state-of-the-art GCM simulations enables us to quantify the mitigation potential of the projected circulation change for three coral reef ecosystems under two future scenarios. Estimated historical trends indicate that over 100% of the large-scale warming to date has been offset locally by changes in circulation, while future simulations predict a warming mitigation effect of only 5-10% depending on the island. The pace and extent to which GCM projections overwhelm historical trends will play a key role in defining the fate of marine ecosystems and island communities across the tropical Pacific. PMID- 26880043 TI - Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials. AB - While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along natural salt marsh environmental gradients occurs at epigenetic, but not genetic loci in two salt marsh perennials. We detected significant genetic and epigenetic structure among populations and among subpopulations, but we found multilocus patterns of differentiation to habitat type only in epigenetic variation for both species. In addition, more epigenetic than genetic loci were correlated with habitat in both species. When we analysed genetic and epigenetic variation simultaneously with partial Mantel, we found no correlation between genetic variation and habitat and a significant correlation between epigenetic variation and habitat in Spartina alterniflora. In Borrichia frutescens, we found significant correlations between epigenetic and/or genetic variation and habitat in four of five populations when populations were analysed individually, but there was no significant correlation between genetic or epigenetic variation and habitat when analysed jointly across the five populations. These analyses suggest that epigenetic mechanisms are involved in the response to salt marsh habitats, but also that the relationships among genetic and epigenetic variation and habitat vary by species. Site-specific conditions may also cloud our ability to detect response in replicate populations with similar environmental gradients. Future studies analysing sequence data and the correlation between genetic variation and DNA methylation will be powerful to identify the contributions of genetic and epigenetic response to environmental gradients. PMID- 26880044 TI - Congenital Venous Lymphatic Malformation as an Unusual Source of Premenarchal Vaginal Bleeding. AB - BACKGROUND: Premenarchal vaginal bleeding can present a diagnostic challenge and has not been previously reported in association with congenital venous lymphatic malformation. CASE: A 3-year-old girl presented with intermittent vaginal bleeding since birth. Evaluation showed premenarchal estradiol and gonadotropin hormones, a normal pelvic ultrasound and normal colonoscopy. Examination under anesthesia and vaginoscopy showed a congested appearance of the hymen and vaginal petechiae. Sudden development of a vulvar cyst led to a pelvic magnetic resonance imaging scan, which revealed a venous malformation of the pelvis and vulvar lymphatic cyst. Vaginal bleeding stopped for approximately 6 months after sclerotherapy with doxycycline and ethanol, however recurred and required repeat sclerotherapy. SUMMARY AND CONCLUSION: Congenital venous lymphatic malformations can rarely be associated with premenarchal vaginal bleeding and should be considered when all more common etiologies have been ruled out. Diagnosis is made using magnetic resonance imaging, and treatment might include doxycycline and ethanol sclerotherapy. PMID- 26880045 TI - Prepubertal Vulvar Fibroma: Neoplasm or Physiological Condition? AB - BACKGROUND: Several authors have previously reconsidered vulvar fibroma, a rare prepubertal neoplasm, as a physiological labial asymmetry of early puberty, recommending a conservative approach for all cases, although some required further clarification. CASE: A fibrous mass found in the left labium majus of a 4 year-old girl was surgically removed. Imaging confirmed a relapse after 10 months and a second surgery was performed due to extremely rapid growth. No subsequent relapse occurred after 2 years of follow-up. Diagnosis confirmed prepubertal vulvar fibroma, with positive CD34 and lack of actin, desmin, S100, and estrogen receptors. SUMMARY AND CONCLUSION: A diagnosis of prepubertal labial asymmetry should prompt careful consideration of several variables, such as age, and radiologic and histologic features, in order to differentiate between a physiological condition and a neoplasm. PMID- 26880046 TI - Printed Carbon Nanotube Electronics and Sensor Systems. AB - Printing technologies offer large-area, high-throughput production capabilities for electronics and sensors on mechanically flexible substrates that can conformally cover different surfaces. These capabilities enable a wide range of new applications such as low-cost disposable electronics for health monitoring and wearables, extremely large format electronic displays, interactive wallpapers, and sensing arrays. Solution-processed carbon nanotubes have been shown to be a promising candidate for such printing processes, offering stable devices with high performance. Here, recent progress made in printed carbon nanotube electronics is discussed in terms of materials, processing, devices, and applications. Research challenges and opportunities moving forward from processing and system-level integration points of view are also discussed for enabling practical applications. PMID- 26880047 TI - Multi-functionalized carbon dots as theranostic nanoagent for gene delivery in lung cancer therapy. AB - Theranostics, an integrated therapeutic and diagnostic system, can simultaneously monitor the real-time response of therapy. Different imaging modalities can combine with a variety of therapeutic moieties in theranostic nanoagents. In this study, a multi-functionalized, integrated theranostic nanoagent based on folate conjugated reducible polyethylenimine passivated carbon dots (fc-rPEI-Cdots) is developed and characterized. These nanoagents emit visible blue photoluminescence under 360 nm excitation and can encapsulate multiple siRNAs (EGFR and cyclin B1) followed by releasing them in intracellular reductive environment. In vitro cell culture study demonstrates that fc-rPEI-Cdots is a highly biocompatible material and a good siRNA gene delivery carrier for targeted lung cancer treatment. Moreover, fc-rPEI-Cdots/pooled siRNAs can be selectively accumulated in lung cancer cells through receptor mediated endocytosis, resulting in better gene silencing and anti-cancer effect. Combining bioimaging of carbon dots, stimulus responsive property, gene silencing strategy, and active targeting motif, this multi-functionalized, integrated theranostic nanoagent may provide a useful tool and platform to benefit clinicians adjusting therapeutic strategy and administered drug dosage in real time response by monitoring the effect and tracking the development of carcinomatous tissues in diagnostic and therapeutic aspects. PMID- 26880048 TI - Progesterone response in neonatal endometrium is key to future reproductive health in adolescents. PMID- 26880049 TI - Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma. AB - AIM: The present study investigated the effect of sarcopenia on short- and long term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older. METHODS: Patient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long-term survival data were analyzed. RESULTS: Sarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease-free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis. CONCLUSION: This retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence-free survival after hepatectomy in patients 70 years of age and older with HCC. PMID- 26880050 TI - Do early noun and verb production predict later verb and noun production? Theoretical implications. AB - Many studies have addressed the question of the relative dominance of nouns over verbs in the productive vocabularies of children in the second year of life. Surprisingly, cross-class (noun-to-verb and verb-to-noun) relations between these two lexical categories have seldom been investigated. The present longitudinal study employed observational and parent-report data obtained from thirty mother child dyads at 1;4, 1;8, and 2;0 to examine this issue. Both the Natural Partitions/Relational Relativity (NP/RR) hypothesis and the Emergentist Coalition Model (ECM) predict that having an initial repertoire of common nouns should facilitate the acquisition of novel verbs, whereas only the ECM suggests that children exploit the syntactic and semantic constraints of known verbs to infer the meaning of novel nouns. In line with the ECM, hierarchical regression analyses indicated that the percentages of nouns produced by children at 1;4 predicted later verbs at 1;8, whereas the percentages of verbs produced at 1;8 predicted later nouns at 2;0. PMID- 26880051 TI - Pulmonary hypertension in valve disease: A beast of the past? PMID- 26880052 TI - Evidence for thymectomy in myasthenia gravis: Getting stronger? AB - Thymectomy is part of the therapeutic armamentarium for myasthenia gravis (MG). During the past 80 years, multiple observational studies have shown that thymectomy can potentially fasten stabilization of the disease, reduce the need for corticosteroids, and in some patients lead to complete remission. The benefit from thymectomy in MG is supported by propensity score analysis. A randomized control trial looking at the role of thymectomy in nonthymomatous MG patients was recently completed, but the results are not yet available. The approach and extent of thymectomy remain a topic of intense discussion, particularly with the development of minimally invasive surgery. Although the presence of extracapsular thymic tissue is frequent and well described, the accessibility of these ectopic thymic foci as well as their function and impact on outcome after surgery have been unclear, leading to divergent views between proponents of a maximal cervicomediastinal thymectomy with en bloc resection of all fatty tissue between the thyroid grand and the diaphragm and those of a less extensive approach. In the future, better definition of the type of thymectomy will be important, particularly if prospective studies and randomized trials are performed to compare different surgical approaches. One possibility would be to reserve the term "extended thymectomy" to resection of the thymus with the anterior mediastinal fat between both pleura, the pericardium and diaphragm. More extensive surgery should be specified when it encompasses sites such as the right and left pericardiophrenic angles, the aortopulmonary window, the aortocaval groove and retroinnominate space, and the perithyroid area. PMID- 26880053 TI - How to balance family with career: A man's perspective. PMID- 26880054 TI - Failure mechanisms in denture adhesives. AB - OBJECTIVE: The mechanical properties of bio adhesives in oral care application are expected to be critical in defining the stability and release of devices such as dentures from the oral tissue. A multiscale experimental mechanical approach is used to evaluate the performance of denture adhesive materials. METHODS: The inherent mechanical behavior of denture fixatives was examined by separating adhesive material from a representative polymethyl methacrylate (PMMA) surface using atomic force microscopy (AFM) approaches and compared to macroscopic mechanical testing. RESULTS: Failure of denture adhesive material was found to be critically dependent on the formation of fibrillar structures within the adhesive. Small scale mechanical testing provided evidence for the mechanical properties of the fibrillar structures formed within the adhesive in macroscopic mechanical testing and indicated the importance of the forces required to fail the adhesive at these small length scales in controlling both the maximum forces sustained by the bulk material as well as the ease of separating the adhesive from PMMA surfaces. SIGNIFICANCE: Our results are important in defining the performance of denture fixative materials and their control of adhesive behavior, allowing the potential to tune properties required in the adhesion and removal of dentures. PMID- 26880055 TI - Determination of the Influence of Side-Chain Conformation on Glycosylation Selectivity using Conformationally Restricted Donors. AB - The synthesis of a series of conformationally locked mannopyranosyl thioglycosides in which the C6-O6 bond adopts either the gauche,gauche, gauche,trans, or trans,gauche conformation is described, and their influence on glycosylation stereoselectivity investigated. Two 4,6-O-benzylidene-protected mannosyl thioglycosides carrying axial or equatorial methyl groups at the 6 position were also synthesized and the selectivity of their glycosylation reactions studied to enable a distinction to be made between steric and stereoelectronic effects. The presence of an axial methoxy group at C6 in the bicyclic donor results in a decreased preference for formation of the beta mannoside, whereas an axial methyl group has little effect on selectivity. The result is rationalized in terms of through-space stabilization of a transient intermediate oxocarbenium ion by the axial methoxy group resulting in a higher degree of SN 1-like character in the glycosylation reaction. Comparisons are made with literature examples and exceptions are discussed in terms of pervading steric effects layered on top of the basic stereoelectronic effect. PMID- 26880057 TI - Risk of stroke in patients with mycosis fungoides: A nationwide population-based cohort study. PMID- 26880056 TI - Cost-utility analysis of stenting versus endarterectomy in the International Carotid Stenting Study. AB - BACKGROUND: The International Carotid Stenting Study was a multicenter randomized trial in which patients with symptomatic carotid artery stenosis were randomly allocated to treatment by carotid stenting or endarterectomy. Economic evidence comparing these treatments is limited and inconsistent. AIMS: We compared the cost-effectiveness of stenting versus endarterectomy using International Carotid Stenting Study data. METHODS: We performed a cost-utility analysis estimating mean costs and quality-adjusted life years per patient for both treatments over a five-year time horizon based on resource use data and utility values collected in the trial. Costs of managing stroke events were estimated using individual patient data from a UK population-based study (Oxford Vascular Study). RESULTS: Mean costs per patient (95% CI) were US$10,477 ($9669 to $11,285) in the stenting group (N = 853) and $9669 ($8835 to $10,504) in the endarterectomy group (N = 857). There were no differences in mean quality-adjusted life years per patient (3.247 (3.160 to 3.333) and 3.228 (3.150 to 3.306), respectively). There were no differences in adjusted costs between groups (mean incremental costs for stenting versus endarterectomy $736 (95% CI -$353 to $1826)) or adjusted outcomes (mean quality-adjusted life years gained -0.010 (95% CI -0.117 to 0.097)). The incremental net monetary benefit for stenting versus endarterectomy was not significantly different from zero at the maximum willingness to pay for a quality adjusted life year commonly used in the UK. Sensitivity analyses showed little uncertainty in these findings. CONCLUSIONS: Economic considerations should not affect whether patients with symptomatic carotid stenosis undergo stenting or endarterectomy. PMID- 26880058 TI - Performance of e-ASPECTS software in comparison to that of stroke physicians on assessing CT scans of acute ischemic stroke patients. AB - BACKGROUND: The Alberta Stroke Program Early CT score (ASPECTS) is an established 10-point quantitative topographic computed tomography scan score to assess early ischemic changes. We compared the performance of the e-ASPECTS software with those of stroke physicians at different professional levels. METHODS: The baseline computed tomography scans of acute stroke patients, in whom computed tomography and diffusion-weighted imaging scans were obtained less than two hours apart, were retrospectively scored by e-ASPECTS as well as by three stroke experts and three neurology trainees blinded to any clinical information. The ground truth was defined as the ASPECTS on diffusion-weighted imaging scored by another two non-blinded independent experts on consensus basis. Sensitivity and specificity in an ASPECTS region-based and an ASPECTS score-based analysis as well as receiver-operating characteristic curves, Bland-Altman plots with mean score error, and Matthews correlation coefficients were calculated. Comparisons were made between the human scorers and e-ASPECTS with diffusion-weighted imaging being the ground truth. Two methods for clustered data were used to estimate sensitivity and specificity in the region-based analysis. RESULTS: In total, 34 patients were included and 680 (34 * 20) ASPECTS regions were scored. Mean time from onset to computed tomography was 172 +/- 135 min and mean time difference between computed tomographyand magnetic resonance imaging was 41 +/- 31 min. The region-based sensitivity (46.46% [CI: 30.8;62.1]) of e-ASPECTS was better than three trainees and one expert (p <= 0.01) and not statistically different from another two experts. Specificity (94.15% [CI: 91.7;96.6]) was lower than one expert and one trainee (p < 0.01) and not statistically different to the other four physicians. e-ASPECTS had the best Matthews correlation coefficient of 0.44 (experts: 0.38 +/- 0.08 and trainees: 0.19 +/- 0.05) and the lowest mean score error of 0.56 (experts: 1.44 +/- 1.79 and trainees: 1.97 +/- 2.12). CONCLUSION: e ASPECTS showed a similar performance to that of stroke experts in the assessment of brain computed tomographys of acute ischemic stroke patients with the Alberta Stroke Program Early CT score method. PMID- 26880059 TI - The anterolateral thigh fold-over flap for total and subtotal glossectomy reconstruction. AB - BACKGROUND: We present a fold-over technique for total and subtotal glossectomy reconstruction utilizing the ALT flap with the goal of increasing soft tissue bulk. METHODS: Retrospective review of total and subtotal glossectomy patients undergoing ALT fold-over flap reconstruction from January 2007 to December 2012. RESULTS: Eight patients fit inclusion criteria. Average length of follow-up was 35 months. There were no flap failures. At last follow-up, no patients were tracheostomy dependent. Six out of 8 patients (75%) did not require a g-tube and were able to maintain their weight. Speech intelligibility was good in 6/8 patients (75%). CONCLUSIONS: The ALT fold-over flap technique provides sufficient bulk to allow decannulation and airway protection as well as PO intake in most patients. Given the minimal donor site morbidity, it is our technique of choice for total and subtotal glossectomy defects. (c) 2016 Wiley Periodicals, Inc. Microsurgery 36:297-302, 2016. PMID- 26880061 TI - Cancer Multidisciplinary Teams can be a Valuable and an Effective Use of a Clinician's Time. PMID- 26880060 TI - The utility of ultrasound elastography in differentiation of endometriomas and hemorrhagic ovarian cysts. AB - PURPOSE: To investigate the feasibility of acoustic radiation force impulse imaging in differentiation of endometriomas and hemorrhagic ovarian cysts. MATERIALS AND METHODS: We evaluated 84 ovarian cysts with high internal echogenicity diagnosed in 70 consecutive women. We excluded simple cysts and hemorrhagic cysts containing septations or mural nodules with detectable flow on Doppler ultrasonography. We obtained the elastographic shear wave velocity (SWV) value of the cysts that could be endometriomas or hemorrhagic ovarian cysts. RESULTS: Among the 78 ovarian cysts in 70 women without any septation or mural nodule, there were 42 endometriomas and 36 hemorrhagic ovarian cysts. Analysis of median SWV values of the ovarian cysts showed that the endometriomas had considerably higher levels of stiffness compared to the hemorrhagic ovarian cysts [median SWV 4.20 +/- 0.42 vs 2.54 +/- 1.04 m/s, p < 0.001]. A SWV cutoff value greater than 3.81 m/s yielded sensitivity and specificity values of 82.1 and 79.2 % respectively, for differentiation of endometriomas from hemorrhagic ovarian cysts. CONCLUSION: Sonoelastography is a novel imaging technique that enables us to evaluate the stiffness of adnexal lesions. The accurate discrimination of endometriomas and hemorrhagic ovarian cysts is important for avoiding unnecessary surgical procedures. ARFI imaging has a high sensitivity and specificity for distinguishing endometrioma from hemorrhagic ovarian cysts. PMID- 26880062 TI - Radiation Exposure and Health Effects - is it Time to Reassess the Real Consequences? AB - Our acceptance of exposure to radiation is somewhat schizophrenic. We accept that the use of high doses of radiation is still one of the most valuable weapons in our fight against cancer, and believe that bathing in radioactive spas is beneficial. On the other hand, as a species, we are fearful of exposure to man made radiation as a result of accidents related to power generation, even though we understand that the doses are orders of magnitude lower than those we use everyday in medicine. The 70th anniversary of the detonation of the atomic bombs in Hiroshima and Nagasaki was marked in 2015. The 30th anniversary of the Chernobyl nuclear power plant accident will be marked in April 2016. March 2016 also sees the fifth anniversary of the accident at the Fukushima nuclear power plant. Perhaps now is an opportune time to assess whether we are right to be fearful of the effects of low doses of radiation, or whether actions taken because of our fear of radiation actually cause a greater detriment to health than the direct effect of radiation exposure. PMID- 26880063 TI - Targeting the MET Pathway in Gastric and Oesophageal Cancers: Refining the Optimal Approach. AB - Gastric and oesophageal cancers are a major cause of global cancer-related morbidity and mortality. Improvements in treatment for locoregional and metastatic gastric and oesophageal cancer have been incremental and the overall prognosis remains poor. Increasingly, molecular classification has identified recurrent, therapeutically relevant, somatic alterations in gastroesophageal malignancies. However, other than ERBB2 amplification, molecularly directed therapies have not translated to improved survival. Amplification of the receptor tyrosine kinase MET is found in about 5% of gastroesophageal cancers and represents an oncogenic driver and therapeutic target. Small series have shown activity of MET-directed tyrosine kinase inhibitors, but the clinical benefit of anti-MET antibodies has been disappointing. Here we discuss the MET pathway in gastroesophageal cancers, the clinical data for MET small molecule tyrosine kinase inhibitors, anti-MET antibodies and future clinical directions for targeting MET in gastric and oesophageal cancers. To our knowledge, this is the most comprehensive review of the clinical experience with MET-directed therapies in gastric and oesophageal cancers. PMID- 26880064 TI - Changes in Patterns of Intensity-modulated Radiotherapy Verification and Quality Assurance in the UK. AB - AIMS: Between 2012 and 2014 the number of patients treated in the UK with intensity-modulated radiotherapy (IMRT) techniques increased significantly. One reason for this was the radiotherapy innovation fund for the centres in England. Before the announcement of the fund, a survey of radiotherapy centres was carried out in 2012 which collected data on IMRT uptake, obstacles to implementation, equipment used, delivery techniques and verification methods. A repeat survey was carried out in 2014 to identify key changes to IMRT quality assurance and verification practices. MATERIALS AND METHODS: An online questionnaire was sent out to all 65 UK radiotherapy centres in the summer of 2012 and again in the summer of 2014. Questions covered background and equipment, machine tolerance and quality assurance, machine-based verification, software-based verification and future plans. RESULTS: There have been significant changes in the delivery techniques used for IMRT, with more than twice as many centres reporting the use of volumetric-modulated arc therapy techniques in 2014 compared with 2012. This has been combined with an increase in Monte Carlo-based algorithms in treatment planning systems. In 2012 all centres reported the need to carry out machine based measurements for IMRT plan verification, dropping to 93% in 2014. Nineteen per cent of centres now report making only one measurement per month for prostate plans and 8% of breast plans never have physical measurements. Most centres use detector arrays for quality assurance measurement (86% in 2012 and 91% in 2014), but a significant number still use film and/or ionisation chambers (51% and 41%). In the analysis of these measurements there has been an increase in the use of tighter criteria. There has been a significant increase in the use of software for verification from 63% in 2012 to 95% in 2014. All centres reported that they needed further resources in order to efficiently achieve the quality assurance required for the number of patients planned to be treated in their centre. CONCLUSIONS: The increased numbers of patients being treated with IMRT has meant that there have been significant changes in the way that quality assurance is carried out. These have been mainly in the reduction of measurements and the increase in software-based verification. However, quality assurance is still a significant burden and still has an effect on the numbers of patients who can be treated with IMRT. PMID- 26880065 TI - In Silico Analysis of FMR1 Gene Missense SNPs. AB - The FMR1 gene, a member of the fragile X-related gene family, is responsible for fragile X syndrome (FXS). Missense single-nucleotide polymorphisms (SNPs) are responsible for many complex diseases. The effect of FMR1 gene missense SNPs is unknown. The aim of this study, using in silico techniques, was to analyze all known missense mutations that can affect the functionality of the FMR1 gene, leading to mental retardation (MR) and FXS. Data on the human FMR1 gene were collected from the Ensembl database (release 81), National Centre for Biological Information dbSNP Short Genetic Variations database, 1000 Genomes Browser, and NHLBI Exome Sequencing Project Exome Variant Server. In silico analysis was then performed. One hundred-twenty different missense SNPs of the FMR1 gene were determined. Of these, 11.66 % of the FMR1 gene missense SNPs were in highly conserved domains, and 83.33 % were in domains with high variety. The results of the in silico prediction analysis showed that 31.66 % of the FMR1 gene SNPs were disease related and that 50 % of SNPs had a pathogenic effect. The results of the structural and functional analysis revealed that although the R138Q mutation did not seem to have a damaging effect on the protein, the G266E and I304N SNPs appeared to disturb the interaction between the domains and affect the function of the protein. This is the first study to analyze all missense SNPs of the FMR1 gene. The results indicate the applicability of a bioinformatics approach to FXS and other FMR1-related diseases. I think that the analysis of FMR1 gene missense SNPs using bioinformatics methods would help diagnosis of FXS and other FMR1 related diseases. PMID- 26880066 TI - Amyloid-beta peptides in interaction with raft-mime model membranes: a neutron reflectivity insight. AB - The role of first-stage beta-amyloid aggregation in the development of the Alzheimer disease, is widely accepted but still unclear. Intimate interaction with the cell membrane is invoked. We designed Neutron Reflectometry experiments to reveal the existence and extent of the interaction between beta-amyloid (Abeta) peptides and a lone customized biomimetic membrane, and their dependence on the aggregation state of the peptide. The membrane, asymmetrically containing phospholipids, GM1 and cholesterol in biosimilar proportion, is a model for a raft, a putative site for amyloid-cell membrane interaction. We found that the structured-oligomer of Abeta(1-42), its most acknowledged membrane-active state, is embedded as such into the external leaflet of the membrane. Conversely, the Abeta(1-42) unstructured early-oligomers deeply penetrate the membrane, likely mimicking the interaction at neuronal cell surfaces, when the Abeta(1-42) is cleaved from APP protein and the membrane constitutes a template for its further structural evolution. Moreover, the smaller Abeta(1-6) fragment, the N-terminal portion of Abeta, was also used. Abeta N-terminal is usually considered as involved in oligomer stabilization but not in the peptide-membrane interaction. Instead, it was seen to remove lipids from the bilayer, thus suggesting its role, once in the whole peptide, in membrane leakage, favouring peptide recruitment. PMID- 26880069 TI - Long-term effects of lowering the alcohol minimum purchasing age on traffic crash injury rates in New Zealand. AB - INTRODUCTION AND AIMS: In December 1999, New Zealand lowered the alcohol minimum purchasing age from 20 to 18 years. We tested hypotheses that this change was associated with long-term increases in traffic injury attributable to alcohol impaired driving among 18- to 19-year-olds (target age group) and 15- to 17-year olds (affected by 'trickle-down'). DESIGN AND METHODS: We undertook a controlled before-and-after comparison of rates of fatal and non-fatal traffic injury to persons of any age attributable to impaired drivers aged 18-19 years and 15-17 years, versus 20- to 21-year-olds. Crash data including assessment of driver alcohol impairment were recorded by New Zealand Police. The pre-change period was 1996-1999. Post-change periods were 2000-2003, 2004-2007 and 2008-2010. Outcomes were population-based and vehicle travel-based rates. RESULTS: Compared with the change in injury rates attributable to alcohol-impaired 20- to 21-year-old male drivers, injuries attributable to 18- to 19-year-old male drivers increased in all post-change periods and significantly so in the second post-change period (incidence rate ratio [IRR] 1.3, 95% confidence interval [CI] 1.1 to 1.5). For 15 to 17-year-old male drivers, rates increased in all post-change periods compared with 20- to 21-year-olds, and more so in the second (IRR 1.2, 95% CI 1.1 to 1.4) and third (IRR 1.2, 95% CI 1.1 to 1.4) periods. There was a short-term relative increase in harm attributable to 18- to 19-year-old female drivers (IRR 1.5; 1.1 to 2.0). Results were similar for vehicle travel-based rates. DISCUSSION AND CONCLUSIONS: Reducing the alcohol minimum purchasing age was followed by long term increases in the incidence of traffic injury attributable to male 15- to 19 year-old alcohol-impaired drivers. [Kypri K, Davie G, McElduff P, Langley J, Connor J. Long-term effects of lowering the alcohol minimum purchasing age on traffic crash injury rates in New Zealand. Drug Alcohol Rev 2017;36:178-185]. PMID- 26880070 TI - Observation of magnetic anomalies in one-step solvothermally synthesized nickel cobalt ferrite nanoparticles. AB - Magnetic anomalies corresponding to the Verwey transition and reorientation of anisotropic vacancies are observed at 151 K and 306 K, respectively, in NiCoFe2O4 nanoparticles (NPs) synthesized by a modified-solvothermal method followed by annealing. Cationic disorder and spherical shape induced non-stoichiometry suppress the Verwey transition in the as-synthesized NPs. On the other hand, reorientation of anisotropic vacancies is quite robust. XRD and electron microscopy investigations confirm a single phase spinel structure and the surface morphology of the as-synthesized NPs changes from spherical to octahedral upon annealing. Rietveld analysis reveals that the Ni(2+) ions migrate from tetrahedral (A) to octahedral (B) sites upon annealing. The Mossbauer results show canted spins in both the NPs and the strength of superexchange is stronger in Co-O-Fe than Ni-O-Fe. Magnetic force images show that the as-synthesised NPs are single-domain whereas the annealed NPs are multi-domain octahedral particles. The FMR study reveals that both the NPs have a broad FMR line-width; and resonance properties are consistent with the random anisotropy model. The broad inhomogeneous FMR line-width, observation of the Verwey transition, tuning of the magnetic domain structure as well as the magnetic properties suggest that the NiCoFe2O4 ferrite NPs may be promising for future generation spintronics, magneto electronics, and ultra-high-density recording media as well as for radar absorbing applications. PMID- 26880068 TI - Molecular optimization of rabies virus glycoprotein expression in Pichia pastoris. AB - In this work, different approaches were investigated to enhance the expression rabies virus glycoprotein (RABV-G) in the yeast Pichia pastoris; this membrane protein is responsible for the synthesis of rabies neutralizing antibodies. First, the impact of synonymous codon usage bias was examined and an optimized RABV-G gene was synthesized. Nevertheless, data showed that the secretion of the optimized RABV-G gene was not tremendously increased as compared with the non optimized one. In addition, similar levels of RABV-G were obtained when alpha factor mating factor from Saccharomyces cerevisiae or the acid phosphatase PHO1 was used as a secretion signal. Therefore, sequence optimization and secretion signal were not the major bottlenecks for high-level expression of RABV-G in P. pastoris. Unfolded protein response (UPR) was induced in clones containing high copy number of RABV-G expression cassette indicating that folding was the limiting step for RABV-G secretion. To circumvent this limitation, co overexpression of five factors involved in oxidative protein folding was investigated. Among these factors only PDI1, ERO1 and GPX1 proved their benefit to enhance the expression. The highest expression level of RABV-G reached 1230 ng ml(-1). Competitive neutralizing assay confirmed that the recombinant protein was produced in the correct conformational form in this host. PMID- 26880071 TI - Does the Medicare Part D Decision-Making Experience Differ by Rural/Urban Location? AB - PURPOSE: Although much has been written about Medicare Part D enrollment, much less is known about beneficiaries' personal experiences with choosing a Part D plan, especially among rural residents. This study sought to address this gap by examining geographic differences in Part D enrollees' perceptions of the plan decision-making process, including their confidence in their choice, their knowledge about the program, and their satisfaction with available information. METHODS: We used data from the 2012 Medicare Current Beneficiary Survey and included adults ages 65 and older who were enrolled in Part D at the time of the survey (n = 3,706). We used ordered logistic regression to model 4 outcomes based on beneficiaries' perceptions of the Part D decision-making and enrollment process, first accounting only for differences by rurality, then adjusting for sociodemographic, health, and coverage characteristics. FINDINGS: Overall, half of all beneficiaries were not very confident in their Part D knowledge. Rural beneficiaries had lower odds of being confident in the plan they chose and in being satisfied with the amount of information available to them during the decision-making process. After adjusting for all covariates, micropolitan residents continued to have lower odds of being confident in the plan that they chose. CONCLUSIONS: Policy-makers should pay particular attention to making information about Part D easily accessible for all beneficiaries and to addressing unique barriers that rural residents have in accessing information while making decisions, such as reduced Internet availability. Furthermore, confidence in the decision-making process may be improved by simplifying the Part D program. PMID- 26880072 TI - Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats. AB - BACKGROUND: This study determines whether 8-week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age matched rats. METHODS: The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. RESULTS: The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: 78+/-2.8 vs. HFD: 87+/-3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58+/-0.07 vs. HFD: 0.40+/ 0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0+/-536.0 vs. HFD: 1,6507.8+/-661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8 week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001). The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25+/-10.54 mmHg and 8-week HFD-treated: 165+/-5.8 mmHg) (P=0.0001), when compared to BP values in 5-week ND, 137+/-4.24 mmHg and 8-week ND, 131.75+/-5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. CONCLUSION: We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function. PMID- 26880073 TI - Women's dietary diversity scores and childhood anthropometric measurements as indices of nutrition insecurity along the urban-rural continuum in Ouagadougou, Burkina Faso. AB - BACKGROUND: Malnutrition is still prevalent worldwide, and its severity, which differs between regions and countries, has led to international organisations proposing its inclusion in the global development framework that will succeed the Millennium Development Goals (post-2015 framework). In Sub-Saharan Africa, malnutrition is particularly severe, among women and children under 5 years. The prevalence of malnutrition has been reported worldwide, differing from region to region and country to country. Nevertheless, little is known about how malnutrition differs between multiple locations along an urban-rural continuum. OBJECTIVE: A survey was carried out in and around Ouagadougou, Burkina Faso, between August and September 2014 to map household nutrition insecurity along the urban-rural continuum, using a transect approach to guide the data collection. DESIGN: Transects of 70 km long and 2 km wide directed radially from the city centre outwards were laid, and data were collected from randomly selected households along these transects. Women's dietary diversity scores (WDDSs) were calculated from a sample of 179 women of reproductive age (15-49 years) from randomly selected households. Additionally, anthropometric data (height/length and weight) of 133 children under 5 years of age were collected along the same transects for the computation of anthropometric indices. RESULTS: We found that relative proportions of the nutrition indices such as stunting, wasting and underweight varied across the urban-rural continuum. Rural households (15%) had the highest relative proportion of WDDS compared with urban households (11%) and periurban households (8%). There was a significant association between children under 5 years' nutritional status (wasting, stunting and underweight) and spatial location (p=0.023). The level of agricultural activities is a possible indicator of wasting in children aged 6-59 months (p=0.032). CONCLUSION: Childhood undernutrition certainly has a spatial dimension that is highly influenced by the degree of urbanity, which should be taken into consideration in policy formulation and implementation. PMID- 26880074 TI - Id2 regulates hyporesponsive invariant natural killer T cells. AB - While the invariant natural killer T (iNKT)-cell response to primary stimulation with the glycolipid, alpha-galactosylceramide (alphaGalCer), is robust, the secondary response to this stimulus is muted resulting in a hyporesponsive state characterized by anti-inflammatory interleukin-10 (IL-10) production and high expression of programmed cell death 1 (PD1) and neuropilin 1 (NRP1). The E protein transcription factors and their negative regulators, the Id proteins, have previously been shown to regulate iNKT cell thymic development, subset differentiation and peripheral survival. Here, we provide evidence that the expression of the transcriptional regulator Id2 is downregulated upon stimulation of iNKT cells with their cognate antigen. Moreover, loss of Id2 expression by iNKT cells resulted in a hyporesponsive state, with splenic Id2-deficient iNKT cells expressing low levels of TBET, high levels of PD1 and NRP1 and production of IL-10 upon stimulation. We propose that downregulation of Id2 expression is an essential component of induction of the anti-inflammatory, hyporesponsive state in iNKT cells. PMID- 26880077 TI - Erratum: Bisphenol-A Induces Podocytopathy With Proteinuria in Mice by Nuria Olea Herrero, Maria Isabel Arenas, Carmen Munoz-Moreno, Rafael Moreno-Gomez-Toledano, Marta Gonzalez-Santander, Ignacio Arribas and Ricardo J. Bosch. PMID- 26880076 TI - Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers. AB - Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We assessed whether these SNPs are associated with polyp multiplicity in proven APC mutation carriers. Sixteen CRC-associated SNPs were analysed in a cohort of 419 APC germline mutation carriers from 182 families. Clinical data were retrieved from the Dutch Polyposis Registry. Allele frequencies of the SNPs were compared for patients with <100 colorectal adenomas versus patients with >=100 adenomas, using generalized estimating equations with the APC genotype as a covariate. We found a trend of association of two of the tested SNPs with the >=100 adenoma phenotype: the C alleles of rs16892766 at 8q23.3 (OR 1.71, 95 % CI 1.05-2.76, p = 0.03, dominant model) and rs3802842 at 11q23.1 (OR 1.51, 95 % CI 1.03-2.22, p = 0.04, dominant model). We identified two risk variants that are associated with a more severe phenotype in APC mutation carriers. These risk variants may partly explain the phenotypic variability in families with the same APC gene defect. Further studies with a larger sample size are recommended to evaluate and confirm the phenotypic effect of these SNPs in FAP. PMID- 26880079 TI - [Richner-Hanhart syndrome]. PMID- 26880075 TI - Maternal mental health in primary care in five low- and middle-income countries: a situational analysis. AB - BACKGROUND: The integration of maternal mental health into primary health care has been advocated to reduce the mental health treatment gap in low- and middle income countries (LMICs). This study reports findings of a cross-country situation analysis on maternal mental health and services available in five LMICs, to inform the development of integrated maternal mental health services integrated into primary health care. METHODS: The situation analysis was conducted in five districts in Ethiopia, India, Nepal, South Africa and Uganda, as part of the Programme for Improving Mental Health Care (PRIME). The analysis reports secondary data on the prevalence and impact of priority maternal mental disorders (perinatal depression, alcohol use disorders during pregnancy and puerperal psychosis), existing policies, plans and services for maternal mental health, and other relevant contextual factors, such as explanatory models for mental illness. RESULTS: Limited data were available at the district level, although generalizable data from other sites was identified in most cases. Community and facility-based prevalences ranged widely across PRIME countries for perinatal depression (3-50 %) and alcohol consumption during pregnancy (5-51 %). Maternal mental health was included in mental health policies in South Africa, India and Ethiopia, and a mental health care plan was in the process of being implemented in South Africa. No district reported dedicated maternal mental health services, but referrals to specialised care in psychiatric units or general hospitals were possible. No information was available on coverage for maternal mental health care. Challenges to the provision of maternal mental health care included; limited evidence on feasible detection and treatment strategies for maternal mental disorders, lack of mental health specialists in the public health sector, lack of prescribing guidelines for pregnant and breastfeeding women, and stigmatising attitudes among primary health care staff and the community. CONCLUSIONS: It is difficult to anticipate demand for mental health care at district level in the five countries, given the lack of evidence on the prevalence and treatment coverage of women with maternal mental disorders. Limited evidence on effective psychosocial interventions was also noted, and must be addressed for mental health programmes, such as PRIME, to implement feasible and effective services. PMID- 26880078 TI - Training in psychiatry throughout Europe. AB - Psychiatry is the largest medical specialty in Europe. Despite efforts to bring harmonisation, training in psychiatry in Europe continues to be very diverse. The Union Europeenne des Medecins Specialistes (UEMS) has issued as from 2000 a charter of requirements for the training in psychiatry with an additional European Framework for Competencies in Psychiatry in 2009. Yet these have not been implemented throughout Europe. In this paper, the diversity in training throughout Europe is approached from different angles: the cultural differences between countries with regards to how mental health care is considered and founded on, the cultural differences between people throughout Europe in all states. The position of psychotherapy is emphasised. What once was the cornerstone of psychiatry as medical specialty seems to have become a neglected area. Seeing the patient with mental health problems within his cultural context is important, but considering him within his family context. The purpose of any training is enabling the trainee to gain the knowledge and acquire the competencies necessary to become a well-equipped professional is the subject of the last paragraph in which trainees consider their position and early career psychiatrists look back to see whether what they were trained in matches with what they need in the working situation. Common standard for training and certification are a necessity within Europe, for the benefit of the profession of psychiatrist but also for patient safety. UEMS is advised to join forces with the Council of National Psychiatric Associations (NPAs) within the EPA and trainings and early career psychiatrist, to discuss with the users what standards should be implemented in all European countries and how a European board examination could ensure professional quality of psychiatrists throughout the continent. PMID- 26880080 TI - [Aphthous ulcers and oral ulcerations]. AB - Aphthous ulcers are painful ulcerations located on the mucous membrane, generally in the mouth, less often in the genital area. Three clinical forms of aphthous ulcers have been described: minor aphthous ulcers, herpetiform aphthous ulcers and major aphthous ulcers. Many other conditions presenting with oral bullous or vesiculous lesions orulcerations and erosions can be mistaken for aphthous ulcers. Currently, treatment of aphthous ulcers is palliative and symptomatic. Topical treatments (topical anesthetics, topical steroids and sucralfate) are the first line therapy. Recurrent aphthous stomatitis (RAS) is defined by the recurrence of oral aphthous ulcers at least 4 times per year. RAS is often idiopathic but can be associated with gastro-intestinal diseases (i.e. celiac disease, inflammatory bowel diseases), nutritional deficiencies (iron, folates...), immune disorders (HIV infection, neutropenia) and rare syndromes. Behcet's disease is a chronic, inflammatory, disease whose main clinical feature is recurrent bipolar aphthosis. Colchicine associated with topical treatments constitutes a suitable treatment of most RAS. Thalidomide is the most effective treatment of RAS but its use is limited by frequent adverse effects. Oral ulcers can be related to a wide range of conditions that constitute the differential diagnoses of aphthous ulcers. Oral ulcers are classified into three main groups: acute ulcers with abrupt onset and short duration, recurrent ulcers (mainly due to postherpetic erythema multiforme) and chronic ulcers (with slow onset and insidious progression). Acute oral ulcers are due to trauma, bacterial infections (including acute necrotizing ulcerative gingivitis), deep fungal infection, gastro-intestinal (namely inflammatory bowel disease) or systemic diseases. Chronic oral ulcers may be drug-induced, or due to benign or malignant tumors. Every oral solitary chronic ulcer should be biopsied to rule out squamous cell carcinoma. A solitary palatal ulcer can be related with necrotizing sialometaplasia. PMID- 26880081 TI - [The NLRP3 inflammasome: Physiopathology and therapeutic application]. AB - The innate immune system constitutes the first line of host defense against pathogens. "Nonself", such as exogenous particles or pathogens, triggers an inflammatory response. Inflammasomes are molecular platforms activated upon cellular infection or stress that trigger the maturation of proinflammatory cytokines such as IL-1beta. Activation of the NLRP3 inflammasome pathway, the most extensively studied, appears to be the corner stone of many inflammatory diseases, including Crohn's disease, rheumatoid arthritis and gout. Cryopyrine associated periodic syndromes (CAPS) are NLRP3 inflammasome-associated diseases. Canakinumab (Ilaris((r))) is the only drug approved for CAPS treatment in France. Targeted therapy against NLRP3 inflammasome and IL-1beta might be the new anti inflammatory drugs. PMID- 26880082 TI - Detrimental Health Effects of Benzene Exposure in Adults After a Flaring Disaster at the BP Refinery Plant in Texas City. AB - OBJECTIVE: To examine the adverse effects of benzene exposure in adults from a prolonged flaring disaster at the BP refinery in Texas City, Texas. METHODS: Adults aged 18 years and older who had been exposed and unexposed to benzene were included. We reviewed medical charts and compared measures of white blood cells (WBCs), platelets, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in exposed and unexposed adults. RESULTS: Records from 2213 adults (benzene exposed, n=1826; unexposed, n=387) were reviewed. Benzene-exposed subjects had significantly higher WBC counts (7.9+/-2.3 vs 6.8+/-1.6*10(3) per uL, P=0.0000) and platelet counts (270.8+/-60.9 vs 242.5+/-53.7*10(3) per uL, P=0.0000) than did the unexposed subjects. Serum creatinine levels were also significantly higher in the exposed group than in the unexposed group (1.0+/-0.2 vs 0.8+/-0.2 mg/dL, P=0.000). Serum levels of ALP were significantly higher in the exposed subjects than in the unexposed subjects (82.1+/-15.6 vs 71.8+/-8.2 IU/L, P=0.000). Similarly, benzene-exposed subjects had significantly higher levels of AST (26.2+/-6.4 vs 19.7+/-5.3 IU/L, P=0.000) and ALT (30.6+/-10.8 vs 20.9+/-9.6 IU/L, P=0.000) than in those unexposed to benzene. CONCLUSION: Benzene exposure resulted in significant alterations in hematologic and liver profiles in adults. PMID- 26880083 TI - Efficacy of three therapy approaches in preschool children with cerebral palsy: a randomized controlled trial. AB - AIM: To examine the efficacy of child-focused, context-focused, and regular care approaches, delivered in a rehabilitation setting by physical or occupational therapists to preschool children with cerebral palsy (CP), in optimizing the child's self-care and mobility capabilities. METHOD: A multicentre randomized controlled trial clustered at therapist level was conducted in 13 rehabilitation centres. It included 68 children with CP (38 males, 30 females; mean age 3y, SD 6mo, range 1y 11mo-4y), classified as Gross Motor Function Classification System levels I to IV, who were already receiving therapy. Children received a child focused, context-focused, or regular care approach during a 6-month period. Self care and mobility capabilities were assessed with the Functional Skills Scale of the Pediatric Evaluation of Disability Inventory. RESULTS: The child-focused, context-focused, and regular care approaches all resulted in significant but similar improvements in self-care (regular: reference; child-focused: beta=-0.11, 95% confidence interval [CI] -0.68 to 0.46; context-focused: beta=0.13, CI -0.38 to 0.64) and mobility (regular: reference; child-focused: beta=-0.09, CI=-0.93 to 0.75; and context-focused: beta=0.14, CI -0.65 to 0.94) capabilities. INTERPRETATION: The results suggest that the three therapy approaches were equally efficacious for preschool children with CP. Depending on a child's individual situation each approach can be selected. PMID- 26880085 TI - Ultrastructural localization of hair keratins, high sulfur keratin-associated proteins and sulfhydryl oxidase in the human hair. AB - Hardening of the human hair shaft during cornification results from the bonding of keratins and keratin-associated proteins. In situ hybridization and light immunocytochemical studies have shown the general distribution of different keratins and some associated proteins but not determined their ultrastructural localization. I report here the localization of hair keratins, two high-sulfur keratin-associated proteins and sulfhydryl oxidase has been studied under the transmission electron microscope in the cornification zone of the human hair. The ultrastructural study on keratin distribution in general confirms previous light microscopic studies. Sulfur-rich KAP1 is mainly cortical but the labeling disappears in fully cornified cortical cells while a diffuse labeling is also present in differentiating cuticle cells. Sulfur-rich K26 immunolocalization is only detected in the exocuticle and endocuticle. Sparse labeling for sulfhydryl oxidase occurs in differentiating cortical cells but is weak and uneven in cuticle cells and absent in medulla and inner root sheath. Labeling disappears in the upper fully cornified cortex and cuticle. The observations indicate that sulfhydryl oxidase and keratin associated proteins are initially produced in the cytoplasm among keratin bundles accumulating in cortical and cuticle cells but these proteins undergo changes during the following cornification that alter the epitopes tagged by the antibodies. PMID- 26880084 TI - Attenuation of teratoma formation by p27 overexpression in induced pluripotent stem cells. AB - BACKGROUND: Pluripotent stem cells, such as embryonic stem cells or induced pluripotent stem cells, have a great potential for regenerative medicine. Induced pluripotent stem cells, in particular, are suitable for replacement of tissue by autologous transplantation. However, tumorigenicity is a major risk in clinical application of both embryonic stem cells and induced pluripotent stem cells. This study explores the possibility of manipulating the cell cycle for inhibition of tumorigenicity. METHODS: We genetically modified mouse induced pluripotent stem cells (miPSCs) to overexpress p27 tumor suppressor and examined their proliferation rate, gene expression, cardiac differentiation, tumorigenicity, and therapeutic potential in a mouse model of coronary artery ligation. RESULTS: Overexpression of p27 inhibited cell division of miPSCs, and that inhibition was dependent on the expression level of p27. p27 overexpressing miPSCs had pluripotency characteristics but lost stemness earlier than normal miPSCs during embryoid body and teratoma formation. These cellular characteristics led to none or smaller teratoma when the cells were injected into nude mice. Transplantation of both miPSCs and p27 overexpressing miPSCs into the infarcted mouse heart reduced the infarction size and improved left ventricular function. CONCLUSIONS: The overexpression of p27 attenuated tumorigenicity by reducing proliferation and earlier loss of stemness of miPSCs. The overexpression of p27 did not affect pluripotency and differentiation characteristics of miPSC. Therefore, regulation of the proliferation rate of miPSCs offers great therapeutic potential for repair of the injured myocardium. PMID- 26880086 TI - Micro-CT analysis of the anatomical characteristics of the stapedial annular ligament. AB - The oval window region has recently been identified as a potential route for drug diffusion into the inner ear. Locally applied gadolinium and trimethylphenylammonium (TMPA) have been shown to directly diffuse into the vestibule through the oval window region. Given the potential importance of the oval window region in the diffusion of substances into the inner ear, this work aimed to use micro-CT to obtain a data set of anatomical characteristics of the annular ligament of the stapes in the human temporal bone, a region thus far poorly studied. Twenty-one temporal bones were micro-dissected to preserve the otic capsule and allow perfusion of fixative stains into the inner ear. The specimens were scanned with micro-CT methods to provide 3D reconstructions and measurement. The 3D reconstructions were able to demonstrate an undisturbed stapes footplate and annular ligament from which measurements could be taken. This study found a wide variance in the volumes and thicknesses of the stapedial ligaments. There was a positive correlation between the size of the stapes footplate and the annular ligament. PMID- 26880087 TI - Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG. AB - OBJECTIVES: Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin. METHODS: Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease. RESULTS: Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release. CONCLUSION: Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria. PMID- 26880088 TI - UK malaria treatment guidelines 2016. AB - 1.Malaria is the tropical disease most commonly imported into the UK, with 1300 1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9. Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet((r))) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim((r))) is an alternative. Quinine or atovaquone-proguanil (Malarone((r))) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram negative bacteraemia/septicaemia. 14. Children with severe malaria should also be treated with empirical broad spectrum antibiotics until bacterial infection can be excluded (Grade 1B). 15. Haemolysis occurs in approximately 10-15% patients following intravenous artesunate treatment. Haemoglobin concentrations should be checked approximately 14 days following treatment in those treated with IV artemisinins (Grade 2C). 16. Falciparum malaria in pregnancy is more likely to be complicated: the placenta contains high levels of parasites, stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. 17. Uncomplicated falciparum malaria in the second and third trimester of pregnancy should be treated with artemether lumefantrine (Grade 2B). Uncomplicated falciparum malaria in the first trimester of pregnancy should usually be treated with quinine and clindamycin but specialist advice should be sought. Severe malaria in any trimester of pregnancy should be treated as for any other patient with artesunate preferred over quinine (Grade 1C). 18. Children with uncomplicated malaria should be treated with an ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine) as first line treatment (Grade 1A). Quinine with doxycycline or clindamycin, or atovaquone proguanil at appropriate doses for weight can also be used. Doxycycline should not be given to children under 12 years. 19. Either an oral ACT or chloroquine can be used for the treatment of non-falciparum malaria. An oral ACT is preferred for a mixed infection, if there is uncertainty about the infecting species, or for P. vivax infection from areas where chloroquine resistance is common (Grade 1B). 20. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine (1A). Primaquine is more effective at preventing relapse if taken at the same time as chloroquine (Grade 1C). 21. Primaquine should be avoided or given with caution under expert supervision in patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. 22. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy and when breastfeeding (until the G6PD status of child is known); after initial treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery or cessation of breastfeeding when hypnozoite eradication can be considered. 23. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas. PMID- 26880089 TI - Normocaloric versus hypocaloric feeding in ICU patients: response to comments by Bitzani. PMID- 26880090 TI - Comments on Marik and Hooper: Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. PMID- 26880092 TI - What Can US Single-Payer Supporters Learn From the Swiss Rejection of Single Payer? AB - On September 27, 2014, Swiss voters rejected a proposal to replace their system of about 60 health insurance companies offering mandatory basic health coverage with a single public insurer, the state, which would offer taxpayer-funded coverage of all medically necessary care. The Swiss and the U.S. media, academia, and business sectors, from conservative and liberal camps, interpreted the results to mean a rejection of single payer and a preference for a privately run system, with important implications for health reform in the United States. While on the surface mainstream interpretations appear reasonable, I argue that they have little basis on fact because they rely on assumptions that, while untrue, are repeated as mantras that conveniently justify the continuation of a model of health insurance that is unraveling, less conspicuously in Switzerland, dramatically in the United States. To make my case, I describe the dominant narrative about Swiss health care and mainstream interpretations of the latest referendum on health reform, unpack the problem within these interpretations, and conclude by identifying what lessons the Swiss referendum contains for single payer advocates in the United States in particular and for those who struggle for social and economic rights more generally. PMID- 26880091 TI - The Intensive Care Global Study on Severe Acute Respiratory Infection (IC GLOSSARI): a multicenter, multinational, 14-day inception cohort study. AB - PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in hospital death that may be useful for risk stratification in these patients. PMID- 26880093 TI - Abdominal aorta rupture secondary to spinal trauma. PMID- 26880094 TI - Studying metal ion binding properties of a three-way junction RNA by heteronuclear NMR. AB - Self-splicing group II introns are highly structured RNA molecules, containing a characteristic secondary and catalytically active tertiary structure, which is formed only in the presence of Mg(II). Mg(II) initiates the first folding step governed by the kappazeta element within domain 1 (D1kappazeta). We recently solved the NMR structure of D1kappazeta derived from the mitochondrial group II intron ribozyme Sc.ai5gamma and demonstrated that Mg(II) is essential for its stabilization. Here, we performed a detailed multinuclear NMR study of metal ion interactions with D1kappazeta, using Cd(II) and cobalt(III)hexammine to probe inner- and outer-sphere coordination of Mg(II) and thus to better characterize its binding sites. Accordingly, we mapped (1)H, (15)N, (13)C, and (31)P spectral changes upon addition of different amounts of the metal ions. Our NMR data reveal a Cd(II)-assisted macrochelate formation at the 5'-end triphosphate, a preferential Cd(II) binding to guanines in a helical context, an electrostatic interaction in the zeta tetraloop receptor and various metal ion interactions in the GAAA tetraloop and kappa element. These results together with our recently published data on Mg(II) interaction provide a much better understanding of Mg(II) binding to D1kappazeta, and reveal how intricate and complex metal ion interactions can be. PMID- 26880096 TI - GP is suspended after prescribing zopiclone for patient to give to neighbours. PMID- 26880097 TI - Cuprous halides semiconductors as a new means for highly efficient light-emitting diodes. AB - In group-III nitrides in use for white light-emitting diodes (LEDs), optical gain, measure of luminous efficiency, is very low owing to the built-in electrostatic fields, low exciton binding energy, and high-density misfit dislocations due to lattice-mismatched substrates. Cuprous halides I-VII semiconductors, on the other hand, have negligible built-in field, large exciton binding energies and close lattice matched to silicon substrates. Recent experimental studies have shown that the luminescence of I-VII CuCl grown on Si is three orders larger than that of GaN at room temperature. Here we report yet unexplored potential of cuprous halides systems by investigating the optical gain of CuCl/CuI quantum wells. It is found that the optical gain and the luminescence are much larger than that of group III-nitrides due to large exciton binding energy and vanishing electrostatic fields. We expect that these findings will open up the way toward highly efficient cuprous halides based LEDs compatible to Si technology. PMID- 26880095 TI - The pedunculopontine tegmental nucleus-A functional hypothesis from the comparative literature. AB - We present data from animal studies showing that the pedunculopontine tegmental nucleus-conserved through evolution, compartmentalized, and with a complex pattern of inputs and outputs-has functions that involve formation and updates of action-outcome associations, attention, and rapid decision making. This is in contrast to previous hypotheses about pedunculopontine function, which has served as a basis for clinical interest in the pedunculopontine in movement disorders. Current animal literature points to it being neither a specifically motor structure nor a master switch for sleep regulation. The pedunculopontine is connected to basal ganglia circuitry but also has primary sensory input across modalities and descending connections to pontomedullary, cerebellar, and spinal motor and autonomic control systems. Functional and anatomical studies in animals suggest strongly that, in addition to the pedunculopontine being an input and output station for the basal ganglia and key regulator of thalamic (and consequently cortical) activity, an additional major function is participation in the generation of actions on the basis of a first-pass analysis of incoming sensory data. Such a function-rapid decision making-has very high adaptive value for any vertebrate. We argue that in developing clinical strategies for treating basal ganglia disorders, it is necessary to take an account of the normal functions of the pedunculopontine. We believe that it is possible to use our hypothesis to explain why pedunculopontine deep brain stimulation used clinically has had variable outcomes in the treatment of parkinsonism motor symptoms and effects on cognitive processing. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26880098 TI - Response of the human tympanic membrane to transient acoustic and mechanical stimuli: Preliminary results. AB - The response of the tympanic membrane (TM) to transient environmental sounds and the contributions of different parts of the TM to middle-ear sound transmission were investigated by measuring the TM response to global transients (acoustic clicks) and to local transients (mechanical impulses) applied to the umbo and various locations on the TM. A lightly-fixed human temporal bone was prepared by removing the ear canal, inner ear, and stapes, leaving the incus, malleus, and TM intact. Motion of nearly the entire TM was measured by a digital holography system with a high speed camera at a rate of 42 000 frames per second, giving a temporal resolution of <24 MUs for the duration of the TM response. The entire TM responded nearly instantaneously to acoustic transient stimuli, though the peak displacement and decay time constant varied with location. With local mechanical transients, the TM responded first locally at the site of stimulation, and the response spread approximately symmetrically and circumferentially around the umbo and manubrium. Acoustic and mechanical transients provide distinct and complementary stimuli for the study of TM response. Spatial variations in decay and rate of spread of response imply local variations in TM stiffness, mass, and damping. PMID- 26880099 TI - Immunoreactions for P53 isoforms are associated with ultrastructural proliferative profiles in benign thyroid nodules. AB - BACKGROUND: P53 isoforms originate from the alternative initiation of P53 gene translation through usage of an internal promoter located in intron 4. All P53 isoforms are spliced in intron 9 and may modulate cell proliferation and cell fate outcome in response to DNA damage. AIM: To examine immunoexpression of P53 isoforms in benign proliferative lesions occurring in multinodular thyroids and to assess the ultrastructural phenotype of P53 distribution in the thyrocytes of those lesions by electron microscopy. MATERIALS AND METHODS: By immunohistochemistry and transmission electron microscopy (TEM), we evaluated 38 multinodular thyroids containing a total of 102 benign lesions: 38 nodular goiters (NG; colloid=20, parenchymatous=18), 52 follicular adenomas (FA) and 12 Hashimoto's thyroditis (HT). FA were classified into 10 normo-follicular, 9 macro follicular, 28 micro-follicular and 5 solid variants. RESULTS: Immunoreaction for P53 isoforms was observed in approximately 50% of all lesions, except macrofollicular variant FA (33%). At TEM analysis, immunoreactive NG, FA and TH lesions showed signs of proliferation by simultaneous appearance of dispersed chromatin, increased amounts of cytoplasmic organelles and dilation of the rough endoplasmic reticulum. TEM signs of apoptosis and proliferation were also detected in FA, but with different rates compared to NG. CONCLUSION: The immunohistochemical expression of P53 isoforms in NG, FA and HT suggests their role in the development of these lesions. Ultrastructural findings support the hypothesis that P53 immunoexpression correlates with reactive proliferative changes in thyrocytes. PMID- 26880100 TI - Synthesis of N-heterocyclic carbene-PdCl2-(iso)quinoline complexes and their application in arylamination at low catalyst loadings. AB - A new type of N-heterocyclic carbene-PdCl2-(iso)quinoline complexes 3 were successfully achieved in acceptable to good yields from easily available starting materials under mild conditions, and their structures were unambiguously confirmed using X-ray single crystal diffraction. Furthermore, their catalytic activity toward Buchwald-Hartwig arylamination of aryl chlorides with primary and secondary amines was fully tested. Under the optimal reaction conditions, the expected arylated amines can be obtained in high to excellent yields at low catalyst loadings (0.005-0.05 mol%). It may be worth noting here that comparison of these complexes with other well-defined and easily available NHC-Pd(ii) complexes bearing different N-containing ancillary ligands was also carried out, showing their superior catalytic activity over all others. PMID- 26880101 TI - Sexually transmitted infections and use of contraceptives in women living with HIV in Denmark - the SHADE cohort. AB - BACKGROUND: No Danish guidelines for screening of sexually transmitted infections (STIs) in women living with HIV (WLWH) exist, except for annual syphilis testing. Drug-drug interaction between hormonal contraceptives and some types of highly active antiretroviral therapy (HAART) occurs. We assessed prevalence of STIs, contraceptive choices and predictors of condom use in a cohort of WLWH in Denmark. METHODS: WLWH consecutively enrolled during their outpatient visits from 2011 to 2012. Gynaecological examination and an interview were performed at entry and 6-month follow-up. Inclusion criteria were HIV-1 infection and >= 18 years of age. Exclusion criteria were pregnancy, alcohol- or drug abuse impeding adherence to the protocol. At entry, participants were tested (and where appropriate, treated according to guidelines) for Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, and herpes simplex (HSV-1 and HSV-2). At follow-up, predictors of condom use were estimated in sexually active WLWH. RESULTS: In total, 334 of the 1,392 eligible WLWH in Denmark were included (median age and HIV duration: 42.5 and 11.3 years). Chlamydia trachomatis was present in four individuals (1 %), and six (2 %) tested positive for HSV-2 by PCR. None were positive for Neisseria gonorrhoeae, HSV-1 or had active syphilis. At follow-up, 252 (76 %) participated; 168 (70 %) were sexually active. Contraceptives were used by 124 (75 %); condoms were preferred (62 %). Having an HIV-negative partner predicted condom use (adjusted OR 3.89 (95 %CI 1.49-10.11)). In the group of participants of reproductive age without pregnancy desires 13 % used no birth control. Possible drug-drug interaction between hormonal contraceptives and HAART was found in 13/14 WLWH receiving both kinds of medication. CONCLUSION: The prevalence of STIs in WLWH in Denmark was low. The need for annual STI screening is questionable. Condoms were preferred contraceptives, especially in WLWH with an HIV-negative partner. In this cohort, 13 % of WLWH of reproductive age were at risk of unintended pregnancies due to lack of birth-control. Finally, in the subgroup of WLWH receiving both hormonal contraceptives and HAART possible drug drug interactions could occur. PMID- 26880102 TI - A New Strategy to Evaluate Technical Efficiency in Hospitals Using Homogeneous Groups of Casemix : How to Evaluate When There is Not DRGs? AB - The public health system has restricted economic resources. Because of that, it is necessary to know how the resources are being used and if they are properly distributed. Several works have applied classical approaches based in Data Envelopment Analysis (DEA) and Stochastic Frontier Analysis (SFA) for this purpose. However, if we have hospitals with different casemix, this is not the best approach. In order to avoid biases in the comparisons, other works have recommended the use of hospital production data corrected by the weights from Diagnosis Related Groups (DRGs), to adjust the casemix of hospitals. However, not all countries have this tool fully implemented, which limits the efficiency evaluation. This paper proposes a new approach for evaluating the efficiency of hospitals. It uses a graph-based clustering algorithm to find groups of hospitals that have similar production profiles. Then, DEA is used to evaluate the technical efficiency of each group. The proposed approach is tested using the production data from 2014 of 193 Chilean public hospitals. The results allowed to identify different performance profiles of each group, that differs from other studies that employs data from partially implemented DRGs. Our results are able to deliver a better description of the resource management of the different groups of hospitals. We have created a website with the results ( bioinformatic.diinf.usach.cl/publichealth ). Data can be requested to the authors. PMID- 26880103 TI - Porcine parvovirus infection activates mitochondria-mediated apoptotic signaling pathway by inducing ROS accumulation. AB - BACKGROUND: Porcine parvovirus (PPV) infection primarily causes reproductive failure of pregnant swine and results in host cell death. Boars, as an important disseminator, shed PPV to sows via semen. PPV infects and numerously replicates in boar testicle, which results in damage of swine testicle in vivo. Reactive oxygen species (ROS), a mediator of cell apoptosis, play a crucial role in the mitochondria apoptotic pathway. However, whether PPV infection induces ST cells apoptosis and ROS accumulation is still unclear. METHODS: To determine the effects of PPV infection on the apoptosis, we detected morphological changes, DNA ladder, activities of caspases, and expression of PARP in PPV-infected ST cells. Moreover, aiming to investigate the effect of PPV infection on the mitochondrial apoptotic pathway and ROS accumulation, we detected the Deltapsim, apoptosis related genes, and ROS. To investigate the role of ROS in the process of PPV induced apoptosis, the ST cells were infected with PPV and treated with the ROS antioxidants. The ROS level was measured using Reactive Oxygen Species Assay Kit and the Deltapsim, expression level of Bcl-2, translocation of Bax, and redistribution of mitochondria cytochrome c were tested. RESULTS: In this study, we demonstrated that PPV infection could induce apoptosis that was characterized by morphological changes, DNA fragmentation and activation of caspases. Moreover, PPV infection suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, decreased the mitochondrial transmembrane potential, and triggered the release of cytochrome c, which caused the subsequent activation of caspase-9 and caspase-3 and initiation of apoptosis. However, during the process of PPV-induced apoptosis, the protein levels of Fas and FasL were not affected. Further studies showed that PPV infection caused ROS accumulation. Inhibition of ROS could reduce mitochondrial transmembrane potential and could significantly block ST cells apoptosis via suppressing Bax translocation, cytochrome c and caspase-3 activation. CONCLUSIONS: All these results suggest that PPV-induced ROS accumulation mediates apoptosis in ST cells, which provided theoretical basis for the molecular pathogenesis of PPV infection. PMID- 26880104 TI - Pentraxin-3 as a marker of disease severity and risk of death in patients with necrotizing soft tissue infections: a nationwide, prospective, observational study. AB - BACKGROUND: New biomarkers are needed to assess the severity of necrotizing soft tissue infection (NSTI) at an early stage and to individualize treatment strategies. We assessed pentraxin-3 (PTX3) as a marker of disease severity and risk of death in patients with NSTI. METHODS: We conducted a prospective, observational study in the intensive care unit at Copenhagen University Hospital, where treatment of NSTI is centralized at a national level. We compared PTX3, procalcitonin and C-reactive protein in septic shock versus nonshock patients and in amputated versus nonamputated patients using the Mann-Whitney U test. The prognostic value of the markers for 180-day mortality was assessed using Cox regression analyses. RESULTS: Patients with NSTI (n = 135) were included over 25 months with up to 2.5-year follow-up; 71% had septic shock, amputation was undertaken in 20% and the 180-day mortality was 27%. Baseline plasma PTX3 level was significantly higher in patients with septic shock (67.3 versus 24.6 ng/mL, p < 0.0001) and in patients who underwent amputation (118.6 versus 43.6 ng/mL, p = 0.019). No significant differences in baseline procalcitonin or C-reactive protein levels were found according to amputation (25.2 versus 7.0 MUg/L, p = 0.060 and 202 versus 225 mg/L, p = 0.123), respectively. Baseline PTX3 level above the median was associated with death (p = 0.009, log-rank test) and the univariate Cox regression analysis revealed a significant association between PTX3 level upon admission and 180-day mortality (hazard ratio 2.60 (95% confidence interval 1.28-5.29), p = 0.008). When adjusted for age, sex, chronic disease and Simplified Acute Physiology Score II, no significant association was found. CONCLUSIONS: High PTX3 level is associated with septic shock, amputation and risk of death in patients with NSTI, but it is not an independent predictor of 180-day mortality in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02180906. Date of registration: June 29, 2014. PMID- 26880105 TI - Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. AB - We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements. PMID- 26880106 TI - Modified RNAs in CRISPR/Cas9: An Old Trick Works Again. AB - Old tricks, new dog: CRISPR/Cas9 is a powerful tool for gene editing that requires an endonuclease (Cas9) and RNA strands. It has been shown that chemical modification of the RNA structures, an approach that has been used to improve the efficiency of RNA interference, can also be applied to enhance the activity of CRISPR/Cas9 and reduce its off-target effects. PMID- 26880107 TI - Experimental warming of a mountain tundra increases soil CO2 effluxes and enhances CH4 and N2O uptake at Changbai Mountain, China. AB - Climatic warming is expected to particularly alter greenhouse gas (GHG) emissions from soils in cold ecosystems such as tundra. We used 1 m(2) open-top chambers (OTCs) during three growing seasons to examine how warming (+0.8-1.2 degrees C) affects the fluxes of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) from alpine tundra soils. Results showed that OTC warming increased soil CO2 efflux by 141% in the first growing season and by 45% in the second and third growing season. The mean CH4 flux of the three growing seasons was -27.6 and 16.7 MUg CH4-C m(-2)h(-1) in the warmed and control treatment, respectively. Fluxes of N2O switched between net uptake and emission. Warming didn't significantly affect N2O emission during the first and the second growing season, but stimulated N2O uptake in the third growing season. The global warming potential of GHG was clearly dominated by soil CO2 effluxes (>99%) and was increased by the OTC warming. In conclusion, soil temperature is the main controlling factor for soil respiration in this tundra. Climate warming will lead to higher soil CO2 emissions but also to an enhanced CH4 uptake with an overall increase of the global warming potential for tundra. PMID- 26880108 TI - Toward a re-interpretation of self-harm: A cross-contextual approach. AB - A common view is that self-harmers are individuals who are exposed to or have been exposed to stressors and hostility in everyday settings. A strand of research has also found that self-harmers expose other people to their hostility. Extending these findings, this study examined whether adolescent self-harmers are simultaneously exposed and expose others to hostility in their everyday interpersonal contexts-at home, at school, and during leisure-time. The participants were 1,482 adolescents, ranging from 13 to 16 years of age, who attended different schools in a medium-sized city in central Sweden. The results show that the adolescents involved in mutually hostile relationships in their different interpersonal contexts exhibited higher self-harm than the adolescents who were exposed to others' hostility or exposed other people to their hostility. Also, the more mutually hostile settings the adolescents were involved in, the more self-harm they reported. Overall, our findings suggest not only that self harmers are exposed to hostility in their different interpersonal contexts, as has been typically assumed, but also that they simultaneously expose others to hostility in these contexts. This has implications for our understanding of young people who harm themselves and also for intervention. Aggr. Behav. 42:522-532, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26880109 TI - Micafungin in invasive fungal infections in children with acute leukemia or undergoing stem cell transplantation. PMID- 26880112 TI - Brain matters: from environmental ethics to environmental neuroethics. AB - The ways in which humans affect and are affected by their environments have been studied from many different perspectives over the past decades. However, it was not until the 1970s that the discussion of the ethical relationship between humankind and the environment formalized as an academic discipline with the emergence of environmental ethics. A few decades later, environmental health emerged as a discipline focused on the assessment and regulation of environmental factors that affect living beings. Our goal here is to begin a discussion specifically about the impact of modern environmental change on biomedical and social understandings of brain and mental health, and to align this with ethical considerations. We refer to this focus as Environmental Neuroethics, offer a case study to illustrate key themes and issues, and conclude by offering a five-tier framework as a starting point of analysis. PMID- 26880111 TI - Altered drug susceptibility during host adaptation of a Plasmodium falciparum strain in a non-human primate model. AB - Infections with Plasmodium falciparum, the most pathogenic of the Plasmodium species affecting man, have been reduced in part due to artemisinin-based combination therapies. However, artemisinin resistant parasites have recently emerged in South-East Asia. Novel intervention strategies are therefore urgently needed to maintain the current momentum for control and elimination of this disease. In the present study we characterize the phenotypic and genetic properties of the multi drug resistant (MDR) P. falciparum Thai C2A parasite strain in the non-human Aotus primate model, and across multiple passages. Aotus infections with C2A failed to clear upon oral artesunate and mefloquine treatment alone or in combination, and ex vivo drug assays demonstrated reduction in drug susceptibility profiles in later Aotus passages. Further analysis revealed mutations in the pfcrt and pfdhfr loci and increased parasite multiplication rate (PMR) across passages, despite elevated pfmdr1 copy number. Altogether our experiments suggest alterations in parasite population structure and increased fitness during Aotus adaptation. We also present data of early treatment failures with an oral artemisinin combination therapy in a pre-artemisinin resistant P. falciparum Thai isolate in this animal model. PMID- 26880110 TI - Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion. AB - Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity. PMID- 26880115 TI - Novel yellowish-green light-emitting Ca10(PO4)6O:Ce(3+) phosphor: structural refinement, preferential site occupancy and color tuning. AB - Here we report a novel Ca10(PO4)6O:Ce(3+) phosphate phosphor, consisting of an apatite structure, whose emission peaks under excitation with near-ultra violet light were found to shift from 410 nm (blue light) to 510 nm (yellowish-green light) with an increasing Ce(3+) doping level due to the Ce(3+) at the different concentrations preferentially occupying different crystallographic sites. PMID- 26880113 TI - Inferences from tip-calibrated phylogenies: a review and a practical guide. AB - Molecular dating of phylogenetic trees is a growing discipline using sequence data to co-estimate the timing of evolutionary events and rates of molecular evolution. All molecular-dating methods require converting genetic divergence between sequences into absolute time. Historically, this could only be achieved by associating externally derived dates obtained from fossil or biogeographical evidence to internal nodes of the tree. In some cases, notably for fast-evolving genomes such as viruses and some bacteria, the time span over which samples were collected may cover a significant proportion of the time since they last shared a common ancestor. This situation allows phylogenetic trees to be calibrated by associating sampling dates directly to the sequences representing the tips (terminal nodes) of the tree. The increasing availability of genomic data from ancient DNA extends the applicability of such tip-based calibration to a variety of taxa including humans, extinct megafauna and various microorganisms which typically have a scarce fossil record. The development of statistical models accounting for heterogeneity in different aspects of the evolutionary process while accommodating very large data sets (e.g. whole genomes) has allowed using tip-dating methods to reach inferences on divergence times, substitution rates, past demography or the age of specific mutations on a variety of spatiotemporal scales. In this review, we summarize the current state of the art of tip dating, discuss some recent applications, highlight common pitfalls and provide a 'how to' guide to thoroughly perform such analyses. PMID- 26880116 TI - High-Performance Perovskite Solar Cells with Enhanced Environmental Stability Based on Amphiphile-Modified CH3 NH3 PbI3. AB - A new aliphatic fluorinated amphiphilic additive is added to CH3 NH3 PbI3 perovskite to tune the morphology and enhance the environmental stability without sacrificing the performance of the devices. Judicious screening of the perovskite precursor solution realizes a power conversion efficiency of 18.0% for mesoporous perovskite solar cells as a result of improved surface coverage. A slower degradation in ambient air is observed with this modified perovskite. PMID- 26880114 TI - Endocannabinoid regulation of beta-cell functions: implications for glycaemic control and diabetes. AB - Visceral obesity is a major risk factor for the development of insulin resistance which can progress to overt type 2 diabetes (T2D) with loss of beta-cell function and, ultimately, loss of beta-cells. Insulin secretion by beta-cells of the pancreatic islets is tightly coupled to blood glucose concentration and modulated by a large number of blood-borne or locally released mediators, including endocannabinoids. Obesity and its complications, including T2D, are associated with increased activity of the endocannabinoid/CB1 receptor (CB1 R) system, as indicated by the therapeutic effects of CB1 R antagonists. Similar beneficial effects of CB1 R antagonists with limited brain penetrance indicate the important role of CB1 R in peripheral tissues, including the endocrine pancreas. Pancreatic beta-cells express all of the components of the endocannabinoid system, and endocannabinoids modulate their function via both autocrine and paracrine mechanisms, which influence basal and glucose-induced insulin secretion and also affect beta-cell proliferation and survival. The present brief review will survey available information on the modulation of these processes by endocannabinoids and their receptors, with an attempt to assess the contribution of such effects to glycaemic control in T2D and insulin resistance. PMID- 26880117 TI - Risk Factors for Subtherapeutic Tacrolimus Levels after Conversion from Continuous Intravenous Infusion to Oral in Children after Allogeneic Hematopoietic Cell Transplantation. AB - Tacrolimus (FK506) is a calcineurin inhibitor and is an essential component of many immunosuppressive regimens. The oral bioavailability of tacrolimus may be affected by many factors, including patient age and gender, as well as by drug drug interactions or genetic polymorphisms in drug metabolism. The dosing recommendations for pediatric allogeneic hematopoietic cell transplantation (alloHCT) recipients have been derived from tacrolimus use in adult solid-organ transplantation patients. Data describing the impact of conversion of i.v. tacrolimus to oral on the incidence of acute graft-versus-host disease (aGVHD) are limited in children after alloHCT. In this study, we describe the incidence of grades II to IV aGVHD after conversion from i.v. tacrolimus to oral tacrolimus and study the clinical factors associated with delayed achievement of therapeutic blood levels. In this retrospective analysis, 68 pediatric patients (median age, 6.7 years; range, .25 to 22 years), underwent alloHCT for malignant and nonmalignant diseases and received tacrolimus and mycophenolate mofetil for aGVHD prophylaxis. Among all patients, the median number of days to achieve therapeutic tacrolimus trough concentration (10 ng/mL to 20 ng/mL) was 7 days (range, 0 to 37 days). Twenty-two patients developed grades II to IV aGVHD and the cumulative incidence of grades II to IV aGVHD in all patients was 32.4% (standard error, .06). On multivariate analysis ethnicity (white versus others: odds ratio [OR], 4.5; 95% confidence interval [95% CI], 1.091 to 18.91; P = .038) and >= 10 days of subtherapeutic tacrolimus levels in first 30 days on i.v. (OR, -3.8; 95% CI, 1.276 to 11.43; P = .017) were significantly associated with delay in achieving therapeutic tacrolimus trough concentration. The impact of race/ethnicity on therapeutic tacrolimus trough concentration in pediatric alloHCT recipients should be further studied prospectively so that individualized dosing plans can be developed. PMID- 26880119 TI - Principal components analysis--K-means transposon element based foxtail millet core collection selection method. AB - BACKGROUND: Core collections are important tools in genetic resources research and administration. At present, most core collection selection criteria are based on one of the following item characteristics: passport data, genetic markers, or morphological traits, which may lead to inadequate representations of variability in the complete collection. The development of a comprehensive methodology that includes as much element data as possible has been explored poorly. Using a collection of (Setaria italica sbsp. italica (L.) P. Beauv.) as a model, we developed a method for core collection construction based on genotype data and numerical representations of agromorphological traits, thereby improving the selection process. RESULTS: Principal component analysis allows the selection of the most informative discriminators among the various elements evaluated, regardless of whether they are genetic or morphological, thereby providing an adequate criterion for further K-mean clustering. Overall, the core collections of S. italica constructed using only genotype data demonstrated overall better validation scores than other core collections that we generated. However, core collection based on both genotype and agromorphological characteristics represented the overall diversity adequately. CONCLUSIONS: The inclusion of both genotype and agromorphological characteristics as a comprehensive dataset in this methodology ensures that agricultural traits are considered in the core collection construction. This approach will be beneficial for genetic resources management and research activities for S. italica as well as other genetic resources. PMID- 26880118 TI - Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma. AB - Three-dimensional cell culture methods are viable in vitro approaches that facilitate the examination of biological features cancer cells present in vivo. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells in porous alginate scaffolds can generate organoid-like spheroids that mimic numerous features of glandular epithelium in vivo, such as acinar morphogenesis and apical expression patterns of EpCAM, a hepatic stem/progenitor cell marker highly expressed in a subset of HCC with stemness features. We show that the activation of Wnt/beta-catenin signaling, an essential pathway for maintaining HCC stemness, is required for EpCAM(+) HCC spheroid formation as well as the maintenance of the acinous structure. Furthermore, we demonstrate that EpCAM(+) HCC cells cultured as spheroids are more sensitive to TGF/beta-induced epithelial-mesenchymal transition with highly tumorigenic and metastatic potential in vivo compared to conventional two-dimensional (2D) culture. In addition, HCC cells in EpCAM(+) spheroids are more resistant to chemotherapeutic agents than 2D-cultured cells. The alginate scaffold-based organotypic culture system is a promising, reliable, and easy system that can be configured into a high throughput fashion for the identification of critical signaling pathways and screening of molecular drug targets specific for HCC. PMID- 26880120 TI - [Not Available]. AB - Different care settings in Quebec use levels of medical intervention forms, also called levels of care (LOC), to determine the code status of patients and to improve end-of-life care planning. It is not currently possible to know whether the levels of care in hospitals benefit patients and staff in facilitating the decision making process of treatment options and resuscitation measures. No study, to the best of the authors' knowledge, has been published about LOC, particularly in Quebec and Canada. This literature review was undertaken on levels of care in order to clarify this topic. Relevant articles are discussed under different themes that are pertinent to LOC. The themes addressed in this article include care at the end of life, do-not-resuscitate orders, treatment withdrawal, and decision making at end of life. PMID- 26880121 TI - Fibroblast growth factor-23 and chronic allograft injury in pediatric renal transplant recipients: a Midwest Pediatric Nephrology Consortium study. AB - The chronic kidney disease-mineral bone disorder (CKD-MBD) produces fibroblast growth factor-23 (FGF-23) and related circulating pathogenic factors that are strongly associated with vascular injury and declining kidney function in native CKD. Similarly, chronic renal allograft injury (CRAI) is characterized by vascular injury and declining allograft function in transplant CKD. We hypothesized that circulating CKD-MBD factors could serve as non-invasive biomarkers of CRAI. We conducted a cross-sectional, multicenter case-control study. Cases (n = 31) had transplant function >20 mL/min/1.73 m(2) and biopsy proven CRAI. Controls (n = 31) had transplant function >90 mL/min/1.73 m(2) and/or a biopsy with no detectable abnormality in the previous six months. We measured plasma CKD-MBD factors at a single time point using ELISA. Median (range) FGF23 levels were over twofold higher in CRAI vs. controls [106 (10-475) pg/mL vs. 45 (8-91) pg/mL; p < 0.001]. FGF23 levels were inversely correlated with transplant function (r(2) = -0.617, p < 0.001). Higher FGF23 levels were associated with increased odds of biopsy-proven CRAI after adjusting for transplant function, clinical, and demographic factors [OR (95% CI) 1.43 (1.23, 1.67)]. Relationships between additional CKD-MBD factors and CRAI were attenuated in multivariable models. Higher FGF23 levels were independently associated with biopsy-proven CRAI in children. PMID- 26880122 TI - Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials. AB - BACKGROUND: Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. METHODS: In this meta analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. FINDINGS: Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2.7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2.16 (95% CI 1.13-4.13), with HRs of roughly 4.0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0.34). These changes underpinned a CAS-versus CEA periprocedural HR of 1.61 (95% CI 0.90-2.88) for patients aged 65-69 years and an HR of 2.09 (1.32-3.32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p>=0.09 for CAS and 0.83 for CEA), or between treatment groups (p=0.84). INTERPRETATION: In these RCTs, CEA was clearly superior to CAS in patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. FUNDING: None. PMID- 26880123 TI - Zika virus outbreak: reproductive health and rights in Latin America. PMID- 26880125 TI - Tungiasis: diagnosis at a glance. PMID- 26880124 TI - Averting a malaria disaster: will insecticide resistance derail malaria control? AB - World Malaria Day 2015 highlighted the progress made in the development of new methods of prevention (vaccines and insecticides) and treatment (single dose drugs) of the disease. However, increasing drug and insecticide resistance threatens the successes made with existing methods. Insecticide resistance has decreased the efficacy of the most commonly used insecticide class of pyrethroids. This decreased efficacy has increased mosquito survival, which is a prelude to rising incidence of malaria and fatalities. Despite intensive research efforts, new insecticides will not reach the market for at least 5 years. Elimination of malaria is not possible without effective mosquito control. Therefore, to combat the threat of resistance, key stakeholders need to rapidly embrace a multifaceted approach including a reduction in the cost of bringing new resistance management methods to market and the streamlining of associated development, policy, and implementation pathways to counter this looming public health catastrophe. PMID- 26880126 TI - Age and carotid intervention outcomes. PMID- 26880127 TI - Feeding ecology of some fish species occurring in artisanal fishery of Socotra Island (Yemen). AB - The demersal species Lethrinus borbonicus, Lethrinus mahsena, Lethrinus microdon, Lethrinus nebulosus, Lutjanus bohar, Lutjanus gibbus, Lutjanus kasmira, Epinephelus fasciatus, Epinephelus stoliczkae, Carangoides gymnostethus and Euthynnus affinis are important coastal fishes species of the northern coast of Socotra (Yemen), exploited by local fishery. The biology and feeding ecology of these species are poorly known in the area. A total of 1239 specimens were sampled from the main fishing landing site of the island (Hadibo). Total length and weight were measured, stomach contents were analyzed, diet overlap, Fulton's Condition index, and trophic levels were estimated. C. gymnostethus, L. microdon and L. kasmira occupied the highest position (T=4.50), L. nebulosus occupied the lower one (TL=3.41). The role of the increasing abundance of small pelagic fish in the diet of many species after the upwelling event is evident, but also different feeding strategies are reported, according to fish ecology. PMID- 26880128 TI - The density-driven circulation of the coastal hypersaline system of the Great Barrier Reef, Australia. AB - The coastal hypersaline system of the Great Barrier Reef (GBR) in the dry season, was investigated for the first time using a 3D baroclinic model. In the shallow coastal embayments, salinity increases to c.a. 10/00 above typical offshore salinity (~35.40/00). This salinity increase is due to high evaporation rates and negligible freshwater input. The hypersalinity drifts longshore north-westward due to south-easterly trade winds and may eventually pass capes or headlands, e.g. Cape Cleveland, where the water is considerably deeper (c.a. 15m). Here, a pronounced thermohaline circulation is predicted to occur which flushes the hypersalinity offshore at velocities of up to 0.08m/s. Flushing time of the coastal embayments is around 2-3weeks. During the dry season early summer, the thermohaline circulation reduces and therefore, flushing times are predicted to be slight longer due to the reduced onshore-offshore density gradient compared to that in the dry season winter period. PMID- 26880129 TI - First comprehensive screening of lipophilic organic contaminants in surface waters of the megacity Jakarta, Indonesia. AB - Jakarta is an Indonesian coastal megacity with over 10 million inhabitants. The rivers flowing through the city receive enormous amounts of untreated wastewaters and discharge their pollutant loads into Jakarta Bay. We utilized a screening approach to identify those site-specific compounds that represent the major contamination of the cities' water resources, and detected a total number of 71 organic contaminants in Jakarta river water samples. Especially contaminants originating from municipal wastewater discharges were detected in high concentrations, including flame retardants, personal care products and pharmaceutical drugs. A flame retardant, a synthetic fragrance and caffeine were used as marker compounds to trace the riverine transport of municipal wastewaters into Jakarta Bay. These markers are also appropriate to trace municipal wastewater discharges to other tropical coastal ecosystems. This application is in particular useful to evaluate wastewater inputs from land-based sources to habitats which are sensitive to changing water quality, like coral reefs. PMID- 26880130 TI - Electrochemical disinfection of simulated ballast water on PbO2/graphite felt electrode. AB - A novel PbO2/graphite felt electrode was constructed by electrochemical deposition of PbO2 on graphite felt and characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) analysis. The prepared electrode is a viable technology for inactivation of Escherichia coli, Enterococcus faecalis, and Artemia salina as indicator organisms in simulated ballast water treatment, which meets the International Maritime Organization (IMO) Regulation D-2. The effects of contact time and current density on inactivation were investigated. An increase in current density generally had a beneficial effect on the inactivation of the three species. E.faecalis and A.salina were more resistant to electrochemical disinfection than E. coli. The complete disinfection of E.coli was achieved in <8min at an applied current density of 253A/m(2). Complete inactivation of E. faecalis and A.salina was achieved at the same current density after 60 and 40min of contact time, respectively. A. salina inactivation follows first-order kinetics. PMID- 26880131 TI - Cross-clamping of bony stumps in preparation for osteosynthesis in digital replantation. PMID- 26880132 TI - Is It Easy to Be a Woman in Science? AB - A total devotion to your science is the main component of success! In this Guest Editorial, I. P. Beletskaya, Professor of chemistry at Moscow State University and a board member of Chemistry--A European Journal, describes her perspective on being a woman in science and shares some personal insights into her career and life as a chemist. PMID- 26880133 TI - Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease. AB - OBJECTIVE: The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. METHODS: Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). RESULTS: EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). CONCLUSIONS: The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD. PMID- 26880135 TI - Bone marrow-derived cells in ocular neovascularization: contribution and mechanisms. AB - Ocular neovascularization often leads to severe vision loss. The role of bone marrow-derived cells (BMCs) in the development of ocular neovascularization, and its significance, is increasingly being recognized. In this review, we discuss their contribution and the potential mechanisms that mediate the effect of BMCs on the progression of ocular neovascularization. The sequence of events by which BMCs participate in ocular neovascularization can be roughly divided into four phases, i.e., mobilization, migration, adhesion and differentiation. This process is delicately regulated and liable to be affected by multiple factors. Cytokines such as vascular endothelial growth factor, granulocyte colony-stimulating factor and erythropoietin are involved in the mobilization of BMCs. Studies have also demonstrated a key role of cytokines such as stromal cell-derived factor-1, tumor necrosis factor-alpha, as well as vascular endothelial growth factor, in regulating the migration of BMCs. The adhesion of BMCs is mainly regulated by vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and vascular endothelial cadherin. However, the mechanisms regulating the differentiation of BMCs are largely unknown at present. In addition, BMCs secrete cytokines that interact with the microenvironment of ocular neovascularization; their contribution to ocular neovascularization, especially choroidal neovascularization, can be aggravated by several risk factors. An extensive regulatory network is thought to modulate the role of BMCs in the development of ocular neovascularization. A comprehensive understanding of the involved mechanisms will help in the development of novel therapeutic strategies related to BMCs. In this review, we have limited the discussion to the recent progress in this field, especially the research conducted at our laboratory. PMID- 26880136 TI - Late Arc/Arg3.1 expression in the basolateral amygdala is essential for persistence of newly-acquired and reactivated contextual fear memories. AB - A feature of fear memory is its persistence, which could be a factor for affective disorders. Memory retrieval destabilizes consolidated memories, and then rapid molecular cascades contribute to early stabilization of reactivated memories. However, persistence of reactivated memories has been poorly understood. Here, we discover that late Arc (also known as Arg3.1) expression in the mouse basolateral amygdala (BLA) is involved in persistence of newly-acquired and reactivated fear memories. After both fear learning and retrieval, Arc levels increased at 2 h, returned to basal levels at 6 h but increased again at 12 h. Inhibiting late Arc expression impaired memory retention 7 d, but not 2 d, after fear learning and retrieval. Moreover, blockade of NR2B-containing N-methyl-D aspartate receptors (NMDARs) prevented memory destabilization and inhibited late Arc expression. These findings indicate that NR2B-NMDAR and late Arc expression plays a critical role in the destabilization and persistence of reactivated memories. PMID- 26880137 TI - Stimulating soil microorganisms for mineralizing the herbicide isoproturon by means of microbial electroremediating cells. AB - The absence of suitable terminal electron acceptors (TEA) in soil might limit the oxidative metabolism of environmental microbial populations. Microbial electroremediating cells (MERCs) consist in a variety of bioelectrochemical devices that aim to overcome electron acceptor limitation and maximize metabolic oxidation with the purpose of enhancing the biodegradation of a pollutant in the environment. The objective of this work was to use MERCs principles for stimulating soil bacteria to achieve the complete biodegradation of the herbicide (14) C-isoproturon (IPU) to (14) CO(2) in soils. Our study concludes that using electrodes at a positive potential [+600 mV (versus Ag/AgCl)] enhanced the mineralization by 20-fold respect the electrode-free control. We also report an overall profile of the (14) C-IPU metabolites and a (14) C mass balance in response to the different treatments. The remarkable impact of electrodes on the microbial activity of natural communities suggests a promising future for this emerging environmental technology that we propose to name bioelectroventing. PMID- 26880138 TI - Cross-sectional survey on awareness of colorectal cancer and a screening programme for primary health care professionals in Catalonia, Spain. AB - This study aimed to assess whether primary health care professionals have accurate information regarding colorectal cancer (CRC) screening procedures, surveillance recommendations and referral strategies. This cross-sectional descriptive study was based on a survey conducted among primary health care professionals in Barcelona, Spain. The questionnaire was used to gather information regarding CRC screening procedures as well as demographic and professional characteristics of the study subjects. A CRC and screening awareness score (ranging from 0 to 12) was created based on the survey questions. The response rate was 58.9% (206/305). The estimated mean score (standard deviation) was 8.43 (SD: 1.30). For four questions, more than 60% of the answers were incorrect: one related to risk factors, two concerning follow-up colonoscopy, and one related to surveillance. Only 30.8% of the participants believed that they were responsible for determining the appropriate surveillance intervals and for scheduling colonoscopies. Although the professionals had sufficient knowledge of CRC screening, professional knowledge of some aspects related to the major non modifiable risk factors for the disease and surveillance colonoscopy procedures could be improved. Frequent communication with professionals is necessary to maintain updated screening-related information. Possible methods for facilitating communication could include continuous briefings, regular message reminders or educational websites. PMID- 26880142 TI - The Two-Minute Radiologist. PMID- 26880140 TI - Mesenchymal Stem/Stromal Cells Derived From a Reproductive Tissue Niche Under Oxidative Stress Have High Aldehyde Dehydrogenase Activity. AB - The use of mesenchymal stem/stromal cells (MSC) in regenerative medicine often requires MSC to function in environments of high oxidative stress. Human pregnancy is a condition where the mother's tissues, and in particular her circulatory system, are exposed to increased levels of oxidative stress. MSC in the maternal decidua basalis (DMSC) are in a vascular niche, and thus would be exposed to oxidative stress products in the maternal circulation. Aldehyde dehydrogenases (ALDH) are a large family of enzymes which detoxify aldehydes and thereby protect stem cells against oxidative damage. A subpopulation of MSC express high levels of ALDH (ALDH(br)) and these are more potent in repairing and regenerating tissues. DMSC was compared with chorionic villous MSC (CMSC) derived from the human placenta. CMSC reside in vascular niche and are exposed to the fetal circulation, which is in lower oxidative state. We screened an ALDH isozyme cDNA array and determined that relative to CMSC, DMSC expressed high levels of ALDH1 family members, predominantly ALDH1A1. Immunocytochemistry gave qualitative confirmation at the protein level. Immunofluorescence detected ALDH1 immunoreactivity in the DMSC and CMSC vascular niche. The percentage of ALDH(br) cells was calculated by Aldefluor assay and DMSC showed a significantly higher percentage of ALDH(br) cells than CMSC. Finally, flow sorted ALDH(br) cells were functionally potent in colony forming unit assays. DMSC, which are derived from pregnancy tissues that are naturally exposed to high levels of oxidative stress, may be better candidates for regenerative therapies where MSC must function in high oxidative stress environments. PMID- 26880141 TI - Reducing routine vaccination dropout rates: evaluating two interventions in three Kenyan districts, 2014. AB - BACKGROUND: Globally, vaccine preventable diseases are responsible for nearly 20% of deaths annually among children <5 years old. Worldwide, many children dropout from the vaccination program, are vaccinated late, or incompletely vaccinated. We evaluated the impact of text messaging and sticker reminders to reduce dropouts from the vaccination program. METHODS: The evaluation was conducted in three selected districts in Kenya: Machakos, Langata and Njoro. Three health facilities were selected in each district, and randomly allocated to send text messages or provide stickers reminding parents to bring their children for second and third dose of pentavalent vaccine, or to the control group (routine reminder) with next appointment date indicated on the well-child booklet. Children aged <12 months presenting for their first dose of pentavalent vaccine were enrolled. A dropout was defined as not returning for vaccination >= 2 weeks after scheduled date for third dose of pentavalent vaccine. We calculated dropout rate as a percentage of the difference between first and third pentavalent dose. RESULTS: We enrolled 1,116 children; 372 in each intervention and 372 controls between February and October 2014. Median age was 45 days old (range: 31-99 days), and 574 (51%) were male. There were 136 (12%) dropouts. Thirteen (4%) children dropped out among those who received text messages, 60 (16%) among who received sticker reminders, and 63 (17%) among the controls. Having a caregiver with below secondary education [Odds Ratio (OR) 1.8, 95% Confidence Interval (CI) 1.1-3.2], and residing >5 km from health facility (OR 1.6, CI 1.0-2.7) were associated with higher odds of dropping out. Those who received text messages were less likely to drop out compared to controls (OR 0.2, CI 0.04-0.8). There was no statistical difference between those who received stickers and controls (OR 0.9, CI 0.5-1.6). CONCLUSION: Text message reminders can reduce vaccination dropout rates in Kenya. We recommend the extended implementation of text message reminders in routine vaccination services. PMID- 26880143 TI - Three-dimensional inverse design of nanopatterns with block copolymers and homopolymers. AB - We propose a facile inverse design strategy to generate three-dimensional (3D) nanopatterns by using either block copolymers or a binary homopolymer blend via dissipative particle dynamics simulations. We find that the composition window of block copolymers to form a specific 3D morphology can be expanded when the self assembly of block copolymers is directed by templates. We also find that a binary homopolymer blend can serve as a better candidate in the inverse templating design, since they have similar performances on recovering the target pattern, with much lower cost. This strategy is proved efficient for fabricating templates with desired topographical configuration, and the inverse design idea sheds lights on better control and design of materials with complex nanopatterns. PMID- 26880144 TI - Pseudomonas syringae pv. phaseolicola isolated from weeds in bean crop fields. AB - Pseudomonas syringae pv. phaseolicola, the causative agent of halo blight in common bean (Phaseolus vulgaris L.), was isolated from weeds associated with bean crops in Spain. The bacterium was recovered from Fumaria sp, Mercurialis annua, Solanum nigrum and Sonchus oleraceus. Ps. s. pv. phaseolicola had previously been isolated from leguminous plants and S. nigrum, but to our knowledge, this is the first time it was recovered from the other three species. The isolates were phenotypically and genetically characterized, and they were compared with isolates recovered from common beans. Five different genotypic profiles were detected by PmeI-PFGE, two of them being of new description. Weed isolates were as pathogenic on bean plants as bean isolates, but they were not pathogenic on S. nigrum. Regarding the survival of the pathogen in weeds, Ps. s. pv. phaseolicola was isolated from So. oleraceus 11 weeks after the end of the bean crop. These results strongly support the idea of weeds as a potential source of inoculum for halo blight in bean. SIGNIFICANCE AND IMPACT OF THE STUDY: It has traditionally been considered that the main source of inoculum of Pseudomonas syringae pv. phaseolicola causing halo blight disease in Phaseolus vulgaris are the bean seeds, and that the host range of the bacterium is almost restricted to leguminous plants. In this study, the bacterium was recovered from four nonleguminous weed species collected in bean fields, and its permanence in weeds for at least 11 weeks after the harvesting of the beans was demonstrated. We have also proved that the strains isolated from weeds were pathogenic on bean plants. Accordingly, the host range of Ps. s. pv. phaseolicola could be broader than previously thought and weeds appear to be acting as a reservoir of the pathogen until the next crop. PMID- 26880145 TI - Surgical Patient Safety Outcomes in Critical Access Hospitals: How Do They Compare? AB - PURPOSE: The aim of the study was to examine whether Critical Access Hospitals (CAHs), the predominant type of hospital in small and isolated rural areas, perform better than, the same as, or worse than Prospective Payment System (PPS) hospitals on measures of quality. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases and American Hospital Association annual survey data were used for analyses. A total of 35,674 discharges from 136 nonfederal general hospitals with fewer than 50 beds were included in the analyses: 14,296 from 100 CAHs and 21,378 from 36 PPS hospitals. Outcome measures included 6 bivariate indicators of adverse events (including complications) of surgical care developed from the Agency for Healthcare Research and Quality's Patient Safety Indicators. Multiple logistic regression models were developed to examine the relationship between hospital adverse events and CAH status. FINDINGS: Compared with PPS hospitals, CAHs are significantly less likely to have any observed (unadjusted) adverse event on 4 of the 6 indicators. After adjusting for patient mix and hospital characteristics, CAHs perform better on 3 of the 6 indicators. Accounting for the number of discharges eliminated the differences between CAHs and PPS hospitals in the likelihood of adverse events across all indicators except one. CONCLUSIONS: The study suggests there are no differences in surgical patient safety outcomes between CAHs and PPS hospitals of comparable size. This reinforces the central role of CAHs in providing quality surgical care to populations in rural and isolated areas, and underscores the importance of strategies to sustain rural surgery infrastructure. PMID- 26880146 TI - Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication. AB - We present the case of a patient who developed delusions and auditory hallucinations and was clinically diagnosed as having schizophrenia. Ten years after the onset of schizophrenia, the disease progressed to mild parkinsonism. SNCA duplication was confirmed. This case expands the spectrum of clinical features in carriers of SNCA duplication. PMID- 26880147 TI - Distinct Processes Drive Diversification in Different Clades of Gesneriaceae. AB - Using a time-calibrated phylogenetic hypothesis including 768 Gesneriaceae species (out of [Formula: see text]3300 species) and more than 29,000 aligned bases from 26 gene regions, we test Gesneriaceae for diversification rate shifts and the possible proximal drivers of these shifts: geographic distributions, growth forms, and pollination syndromes. Bayesian Analysis of Macroevolutionary Mixtures analyses found five significant rate shifts in Beslerieae, core Nematanthus, core Columneinae, core Streptocarpus, and Pacific Cyrtandra These rate shifts correspond with shifts in diversification rates, as inferred by Binary State Speciation and Extinction Model and Geographic State Speciation and Extinction model, associated with hummingbird pollination, epiphytism, unifoliate growth, and geographic area. Our results suggest that diversification processes are extremely variable across Gesneriaceae clades with different combinations of characters influencing diversification rates in different clades. Diversification patterns between New and Old World lineages show dramatic differences, suggesting that the processes of diversification in Gesneriaceae are very different in these two geographic regions. PMID- 26880149 TI - Introductory paragraph. PMID- 26880148 TI - Integrative Taxonomy Recognizes Evolutionary Units Despite Widespread Mitonuclear Discordance: Evidence from a Rotifer Cryptic Species Complex. AB - Mitonuclear discordance across taxa is increasingly recognized as posing a major challenge to species delimitation based on DNA sequence data. Integrative taxonomy has been proposed as a promising framework to help address this problem. However, we still lack compelling empirical evidence scrutinizing the efficacy of integrative taxonomy in relation to, for instance, complex introgression scenarios involving many species. Here, we report remarkably widespread mitonuclear discordance between about 15 mitochondrial and 4 nuclear Brachionus calyciflorus groups identified using different species delimitation approaches. Using coalescent-, Bayesian admixture-, and allele sharing-based methods with DNA sequence or microsatellite data, we provide strong evidence in support of hybridization as a driver of the observed discordance. We then describe our combined molecular, morphological, and ecological approaches to resolving phylogenetic conflict and inferring species boundaries. Species delimitations based on the ITS1 and 28S nuclear DNA markers proved a more reliable predictor of morphological variation than delimitations using the mitochondrial COI gene. A short-term competition experiment further revealed systematic differences in the competitive ability between two of the nuclear-delimited species under six different growth conditions, independent of COI delimitations; hybrids were also observed. In light of these findings, we discuss the failure of the COI marker to estimate morphological stasis and morphological plasticity in the B. calyciflorus complex. By using B. calyciflorus as a representative case, we demonstrate the potential of integrative taxonomy to guide species delimitation in the presence of mitonuclear phylogenetic conflicts. PMID- 26880150 TI - Beliefs in an Unjust World: Mediating Ethnicity-Related Stressors and Psychological Functioning. AB - OBJECTIVE: Racism is negatively associated with health. Explorations of cognitive reactions, such as beliefs in an unjust world (BUW), are needed to understand the associations between both perceived discrimination and own-group conformity pressures (OGCPS) and reduced psychological well-being. METHOD: With a sample of 215 ethnic minority individuals, this study used structural equation modeling to explore BUW's mediating role between the two aforementioned forms of ethnicity related stressors (ERS), anger rumination, and negative affect. RESULTS: ERS were directly positively associated with BUW, anger rumination, and negative affect. BUW were directly and positively associated with both anger rumination and negative affect. Finally, BUW significantly mediated the direct relationships between both ethnicity-related stressors and anger rumination and negative affect. CONCLUSION: Although addressing racism and OGCPS at a systemic level (e.g., policy, prejudice prevention) is needed to reduce ERS, these findings suggest that BUW is one point of possible clinical intervention for individuals who have experienced these stressors. PMID- 26880151 TI - A General and Mild Approach to Controllable Preparation of Manganese-Based Micro- and Nanostructured Bars for High Performance Lithium-Ion Batteries. AB - One-dimensional (1D) micro- and nanostructured electrode materials with controllable phase and composition are appealing materials for use in lithium-ion batteries with high energy and power densities, but they are challenging to prepare. Herein, a novel ethanol-water mediated co-precipitation method by a chimie douce route (synthesis conducted under mild conditions) has been exploited to selectively prepare an extensive series of manganese-based electrode materials, manifesting the considerable generalizability and efficacy of the method. Moreover, by simply tuning the mixed solvent and reagents, transition metal oxide bars with differing aspect ratios and compositions were prepared with an unprecedented uniformity. Application prospects are demonstrated by Li-rich 0.5 Li2 MnO3 ?0.5 LiNi1/3 Co1/3 Mn1/3 O2 bars, which demonstrate excellent reversible capacity and rate capability thanks to the steerable nature of the synthesis and material quality. This work opens a new route to 1D micro- and nanostructured materials by customizing the precipitating solvent to orchestrate the crystallization process. PMID- 26880152 TI - Enablers and barriers for implementing high-quality hypertension care in a rural primary care setting in Nigeria: perspectives of primary care staff and health insurance managers. AB - BACKGROUND: Hypertension is a highly prevalent risk factor for cardiovascular diseases in sub-Saharan Africa (SSA) that can be modified through timely and long term treatment in primary care. OBJECTIVE: We explored perspectives of primary care staff and health insurance managers on enablers and barriers for implementing high-quality hypertension care, in the context of a community-based health insurance programme in rural Nigeria. DESIGN: Qualitative study using semi structured individual interviews with primary care staff (n = 11) and health insurance managers (n=4). Data were analysed using standard qualitative techniques. RESULTS: Both stakeholder groups perceived health insurance as an important facilitator for implementing high-quality hypertension care because it covered costs of care for patients and provided essential resources and incentives to clinics: guidelines, staff training, medications, and diagnostic equipment. Perceived inhibitors included the following: high staff workload; administrative challenges at facilities; discordance between healthcare provider and insurer on how health insurance and provider payment methods work; and insufficient fit between some guideline recommendations and tools for patient education and characteristics/needs of the local patient population. Perceived strategies to address inhibitors included the following: task-shifting; adequate provider payment benchmarking; good provider-insurer relationships; automated administration systems; and tailoring guidelines/patient education. CONCLUSIONS: By providing insights into perspectives of primary care providers and health insurance managers, this study offers information on potential strategies for implementing high-quality hypertension care for insured patients in SSA. PMID- 26880153 TI - The importance of intersectoral factors in promoting equity-oriented universal health coverage: a multilevel analysis of social determinants affecting neonatal infant and under-five mortality in Bangladesh. AB - INTRODUCTION: Health is multidimensional and affected by a wide range of factors, many of which are outside the health sector. To improve population health and reduce health inequality, it is important that we take into account the complex interactions among social, environmental, behavioural, and biological factors and design our health interventions accordingly. OBJECTIVES: This study examines mortality differentials in children of different age groups by key social determinants of health (SDH) including parental education and employment, mother's level of autonomy, age, asset index, living arrangements (utilities), and other geographical contextual factors (area of residence, road conditions). DESIGN: We used data from the two rounds of Bangladesh Health and Demographic Survey, a nationally representative sample survey of the population residing in Bangladesh. Multilevel logistic models were used to study the impact of SDH on child mortality. RESULTS: The study found that the mother's age, the education of both parents, the mother's autonomy to take decisions about matters linked to the health of her child, the household socio-economic conditions, the geographical region of residence, and the condition of the roads were significantly associated with higher risks of neonatal, infant, and under-five mortality in Bangladesh. CONCLUSION: The study findings suggest there are complex relationships among different SDH. Thus larger intersectoral actions will be needed to reduce disparities in child health and mortality and achieve meaningful progress towards equity-oriented universal health coverage. PMID- 26880155 TI - Prenatal smoking and childhood behavior problems: is the association mediated by birth weight? AB - Maternal smoking during pregnancy is associated with both reduced birth weight and adverse neurobehavioral outcomes. The aim of this study was to investigate longitudinal associations between maternal smoking during pregnancy and childhood behavioral outcomes, and to determine the role of birth weight in mediating such associations. The study included 489 mother-child pairs. Prenatal exposures were assessed via maternal interviews conducted on average 1 year after delivery and child behavior assessments were completed at 5-12 years of age using the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF). Maternal smoking during pregnancy was associated with externalizing and total behavior problems according to both mother and teacher report. Maternal smoking was also associated with the following percentage increases in scores: 41% (CBCL) and 44% (TRF) for aggressive behavior and 65% (CBCL) and 47% (TRF) for attention problems. Associations with behavior problems were attenuated or no longer observed for mothers that quit smoking in early pregnancy. The proportion of the total effect of maternal smoking on behavioral outcomes explained by differences in birth weight was small and ranged from 6.6% for externalizing behavior on the CBCL to 20.1% for rule breaking behavior on the CBCL. Our results suggest that birth weight differences explain only a small proportion of the magnitude of association between maternal smoking during pregnancy and selected behavioral outcomes. PMID- 26880154 TI - Communication strategies to promote the uptake of childhood vaccination in Nigeria: a systematic map. AB - BACKGROUND: Effective communication is a critical component in ensuring that children are fully vaccinated. Although numerous communication interventions have been proposed and implemented in various parts of Nigeria, the range of communication strategies used has not yet been mapped systematically. This study forms part of the 'Communicate to vaccinate' (COMMVAC) project, an initiative aimed at building research evidence for improving communication with parents and communities about childhood vaccinations in low- and middle-income countries. OBJECTIVE: This study aims to: 1) identify the communication strategies used in two states in Nigeria; 2) map these strategies against the existing COMMVAC taxonomy, a global taxonomy of vaccination communication interventions; 3) create a specific Nigerian country map of interventions organised by purpose and target; and 4) analyse gaps between the COMMVAC taxonomy and the Nigerian map. DESIGN: We conducted the study in two Nigerian states: Bauchi State in Northern Nigeria and Cross River State in Southern Nigeria. We identified vaccination communication interventions through interviews carried out among purposively selected stakeholders in the health services and relevant agencies involved in vaccination information delivery; through observations and through relevant documents. We used the COMMVAC taxonomy to organise the interventions we identified based on the intended purpose of the communication and the group to which the intervention was targeted. RESULTS: The Nigerian map revealed that most of the communication strategies identified aimed to inform and educate and remind or recall. Few aimed to teach skills, enhance community ownership, and enable communication. We did not identify any intervention that aimed to provide support or facilitate decision-making. Many interventions had more than one purpose. The main targets for most interventions were caregivers and community members, with few interventions directed at health workers. Most interventions identified were used in the context of campaigns rather than routine immunisation programmes. CONCLUSIONS: The identification and development of the Nigerian vaccination communication interventions map could assist programme managers to identify gaps in vaccination communication. The map may be a useful tool as part of efforts to address vaccine hesitancy and improve vaccination coverage in Nigeria and similar settings. PMID- 26880156 TI - Shedding light on the leukodystrophies. PMID- 26880158 TI - A transcriptome study on Macrobrachium rosenbergii hepatopancreas experimentally challenged with white spot syndrome virus (WSSV). AB - The world production of shrimp such as the Malaysian giant freshwater prawn, Macrobrachium rosenbergii is seriously affected by the white spot syndrome virus (WSSV). There is an urgent need to understand the host pathogen interaction between M. rosenbergii and WSSV which will be able to provide a solution in controlling the spread of this infectious disease and lastly save the aquaculture industry. Now, using Next Generation Sequencing (NGS), we will be able to capture the response of the M. rosenbergii to the pathogen and have a better understanding of the host defence mechanism. Two cDNA libraries, one of WSSV challenged M. rosenbergii and a normal control one, were sequenced using the Illumina HiSeqTM 2000 platform. After de novo assembly and clustering of the unigenes from both libraries, 63,584 standard unigenes were generated with a mean size of 698bp and an N50 of 1137bp. We successfully annotated 35.31% of all unigenes by using BLASTX program (E-value <10-5) against NCBI non-redundant (Nr), Swiss-Prot, Kyoto Encyclopedia of Genes and Genome pathway (KEGG) and Orthologous Groups of proteins (COG) databases. Gene Ontology (GO) assessment was conducted using BLAST2GO software. Differentially expressed genes (DEGs) by using the FPKM method showed 8443 host genes were significantly up-regulated whereas 5973 genes were significantly down-regulated. The differentially expressed immune related genes were grouped into 15 animal immune functions. The present study showed that WSSV infection has a significant impact on the transcriptome profile of M. rosenbergii's hepatopancreas, and further enhanced the knowledge of this host virus interaction. Furthermore, the high number of transcripts generated in this study will provide a platform for future genomic research on freshwater prawns. PMID- 26880159 TI - Investigating the significance of the role of Ostrea edulis larvae in the transmission and transfer of Bonamia ostreae. AB - In this study, the ability of oyster larvae, brooded in the pallial cavity of the parent oyster, to become infected in the pallial fluid, which is influenced by the brooding oyster and surrounding environment, was investigated. Larvae were collected over three summers from three areas around Ireland. Samples were screened for the presence of Bonamia ostreae DNA using PCR analysis. Four samples of larvae were found to be positive for B. ostreae DNA, though the parent oysters were negative for infection. Larvae may be able to acquire the pathogen from the water column during filter feeding or elimination of pseudo-faeces by the brooding adult. PMID- 26880157 TI - East London's Homeless: a retrospective review of an eye clinic for homeless people. AB - BACKGROUND: There is very little published work on the visual needs of homeless people. This paper is the first study to investigate the visual needs of homeless people in the UK. Although similar work has been done in other countries, this study is unique because the United Kingdom is the only country with a National Health Service which provides free healthcare at the point of access. This study analysed the refractive status of the sample used, determined the demographics of homeless people seeking eye care and established if there is a need for community eye health with access to free spectacle correction in East London. METHODS: This retrospective case study analysed the clinical records of 1,141 homeless people using the Vision Care for Homeless People services at one of their clinics in East London. All eye examinations were carried out by qualified optometrists and, where appropriate, spectacles were dispensed to patients. Data captured included age, gender, ethnicity and refractive error. Results were analysed using two sample t-tests with Excel and Minitab. RESULTS: Demographics of age, gender and ethnicity are described. Spherical equivalents (SE) were calculated from prescription data available for 841 clinic users. Emmetropia was defined as SE 0.50DS to +1DS, myopia as SE < -0.50DS, and hyperopia as SE > +1DS. The majority of clinic users were male (79.2 %, n = 923). Approximately 80 % (n = 583) of clinic users were white, 10 % (n = 72) were 'black', 4 % (n = 29) 'Asian' and the remaining 5.6 % (n = 40) were of 'mixed ethnicity' and 'other' groups. The mean age of females attending the clinic was significantly lower than that of males (45.9 years, SD = 13.8 vs' 48.4 years, SD = 11.8) when analysed using a two sample t-test (t (317) = 2.44, p = 0.02). One third of service users were aged between 50-59 years. Myopia and hyperopia prevalence rates were 37.0 % and 21.0 % respectively. A total of 34.8 % of homeless people were found to have uncorrected refractive error, and required spectacle correction. CONCLUSIONS: This study has identified a high proportion of uncorrected refractive error in this sample and therefore a need for regular eye examinations and provision of refractive correction for homeless people. PMID- 26880160 TI - Microelectrode array analysis of hippocampal network dynamics following theta burst stimulation via current source density reconstruction by Gaussian interpolation. AB - BACKGROUND: Multielectrode arrays (MEAs) have been used to understand electrophysiological network dynamics by recording real-time activity in groups of cells. The extent to which the collection of such data enables hypothesis testing on the level of circuits and networks depends largely on the sophistication of the analyses applied. NEW METHOD: We studied the systemic temporal variations of endogenous signaling within an organotypic hippocampal network following theta-burst stimulation (TBS) to the Schaffer collateral commissural pathways. The recovered current source density (CSD) information from the raw grid of extracellular potentials by using a Gaussian interpolation method increases spatial resolution and avoids border artifacts by numerical differentials. RESULTS: We compared total sink and source currents in DG, CA3, and CA1; calculated accumulated correlation coefficients to compare pre- with post-stimulation CSD dynamics in each region; and reconstructed functional connectivity maps for regional cross-correlations with respect to temporal CSD variations. The functional connectivity maps for potential correlations pre- and post-TBS were compared to investigate the neural network as a whole, revealing differences post-TBS. COMPARISON WITH EXISTING METHOD(S): Previous MEA work on plasticity in hippocampal evoked potentials has focused on synchronicity across the hippocampus within isolated subregions. Such analyses ignore the complex relationships among diverse components of the hippocampal circuitry, thus failing to capture network-level behaviors integral to understanding hippocampal function. CONCLUSIONS: The proposed method of recovering current source density to examine whole-hippocampal function is sensitive to experimental manipulation and is worth further examination in the context of network-level analyses of neural signaling. PMID- 26880161 TI - Improved FastICA algorithm in fMRI data analysis using the sparsity property of the sources. AB - BACKGROUND: As a blind source separation technique, independent component analysis (ICA) has many applications in functional magnetic resonance imaging (fMRI). Although either temporal or spatial prior information has been introduced into the constrained ICA and semi-blind ICA methods to improve the performance of ICA in fMRI data analysis, certain types of additional prior information, such as the sparsity, has seldom been added to the ICA algorithms as constraints. NEW METHOD: In this study, we proposed a SparseFastICA method by adding the source sparsity as a constraint to the FastICA algorithm to improve the performance of the widely used FastICA. The source sparsity is estimated through a smoothed l0 norm method. We performed experimental tests on both simulated data and real fMRI data to investigate the feasibility and robustness of SparseFastICA and made a performance comparison between SparseFastICA, FastICA and Infomax ICA. RESULTS: Results of the simulated and real fMRI data demonstrated the feasibility and robustness of SparseFastICA for the source separation in fMRI data. COMPARISON WITH EXISTING METHODS: Both the simulated and real fMRI experimental results showed that SparseFastICA has better robustness to noise and better spatial detection power than FastICA. Although the spatial detection power of SparseFastICA and Infomax did not show significant difference, SparseFastICA had faster computation speed than Infomax. CONCLUSIONS: SparseFastICA was comparable to the Infomax algorithm with a faster computation speed. More importantly, SparseFastICA outperformed FastICA in robustness and spatial detection power and can be used to identify more accurate brain networks than FastICA algorithm. PMID- 26880162 TI - Long-term primary culture of neurons taken from chick embryo brain: A model to study neural cell biology, synaptogenesis and its dynamic properties. AB - BACKGROUND: Studying neuronal growth, development and synaptogenesis are among the hot research topics. However, it is faced with various challenges and technical limitations that include but not limited to donor's species and health, threat to life, age of embryo, glial contamination, real-time tracking, and follow-up. NEW METHOD: We have successfully standardized a method for long-term primary culture of neurons collected from post-fertilized 9 day incubated chicken embryo brain overcoming the limitations mentioned above. Fertilized eggs were incubated in the laboratory and neurons from the embryonic brain were collected and low-density culture, apparently without glial contamination, was studied at least for 35 days in vitro (DIV). RESULTS: Neurons were characterized by double immunostaining using stringent neuronal and glial markers. Neuronal differentiation, cytomorphology, neurite and axon formation, development and maturation, spine formation and synaptogenesis were tracked in real-time in a stage and time dependent manner. The neurons were transfected with Synaptophysin RFP to label synaptic vesicles, which were followed in real-time under live-cell imaging. COMPARISON WITH EXISTING METHODS: Every step was carried out under controlled laboratory conditions. Eggs are easily available, easy to handle, neurons from desired day of incubation could be conveniently studied for long period in apparently glia-free condition. In addition to common factors affecting primary culture, selection of culture media and cover glass coating are other key factors affecting neuronal cultures. CONCLUSIONS: We describe an inexpensive, simpler pure primary neuronal culture method for studying neuronal cell-biology, synaptogenesis, vesicular dynamics and it has potential to grow 3D-multilayered brain in vitro. PMID- 26880163 TI - Is Gly16Arg beta2 Receptor Polymorphism Related to Impulse Oscillometry in a Real Life Asthma Clinic Setting? AB - PURPOSE: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. METHODS: Patients with persistent asthma taking inhaled corticosteroid +/- long-acting beta-agonist (ICS +/- LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5-R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use. RESULTS: One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 ug/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified-89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72-1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5-R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57-1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5-R20 > 0.07 kPa/l.s being 69 versus 73 %. CONCLUSION: In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS +/- LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use. PMID- 26880164 TI - DIPNECH: Association Between Histopathology and Clinical Presentation. AB - Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder which can be an incidental finding in imaging tests performed during the investigation of another condition, or is the final diagnosis in patients evaluated for chronic obstructive complaints. To explore the possible association between specific histopathology features and the mode of clinical presentation, we retrieved the clinical, functional, radiological, and pathological data of all 13 patients diagnosed with DIPNECH at our Institution over a 14-year period (2000 2014). As compared to patients with incidental disease (6/13, 46 %), patients with symptomatic disease were younger [mean (SD): 57.7 vs. 68.7 years, p = 0.046], were more likely to have mosaic attenuation (100 vs. 0 %, p = 0.001) and small multiple nodules (100 vs. 17 %, p = 0.005) at CT, and showed a significantly higher number of foci of linear neuroendocrine proliferation [median (IQR): 28 (13-37) vs. 6 (5-13), p = 0.018] and of tumorlets [median (IQR): 10 (8-20) vs. 1 (1-1), p = 0.002] at histology. Incidental disease was found in association with pulmonary adenocarcinoma in five out of six patients (83.3 %). The results of our study provide preliminary evidence that symptomatic patients with DIPNECH represent a specific subset characterized by younger age and a higher burden of foci of neuroendocrine proliferation. PMID- 26880165 TI - Matrix metalloproteinase-based photodynamic molecular beacons for targeted destruction of bone metastases in vivo. AB - The metastatic spread of cancer from the primary site or organ is one of its most devastating aspects, being responsible for up to 90% of cancer-associated mortality. Bone is one of the common sites of metastatic spread, including the vertebrae. Regardless of the treatment strategy, the clinical goals for patients with vertebral metastases are to improve the quality of life by preventing neurologic decline, to achieve durable pain relief and enhance local tumor control. However, in part due to the close proximity of the spinal cord, current treatment options are limited. We propose a novel therapeutic strategy with the use of photodynamic molecular beacons (PMBs) for targeted destruction of spinal metastases, particularly to de-bulk lesions as an adjuvant to vertebroplasty or kyphoplasty in order to mechanically stabilize weak or fractured vertebrae. The PDT efficacy of a matrix metalloproteinase-specific PMB is reported in a metstatic model that recapitulates the clinical features of tumor growth within the bone. We demonstrate that not only does tumor cell destruction occur but also the killing of bone stromal cells. The potential of PMB-PDT to destroy metastatic tumors, disrupt the osteolytic cycle and better preserve critical organs with an increased therapeutic window compared with conventional photosensitizers is demonstrated. PMID- 26880166 TI - [Breastfeeding, complementary feeding and risk of childhood obesity]. AB - OBJECTIVE: To evaluate the pattern of breastfeeding and weaning as a risk of obesity in pre-school children from a Primary Care Unit. DESIGN: Cross-sectional analytical study LOCATION: Cancun, Quintana Roo (Mexico). PARTICIPANTS: Children from 2-4 years of age from a Primary Care Unit. MAIN MEASUREMENTS: Duration of total and exclusive breastfeeding, age and food utilized for complementary feeding reported by the mother or career of the child and nutritional status assessment evaluated by body mass index (BMI) >= 95 percentile. Determination of prevalence ratio (PR), odds ratio (OR), chi squared (x2), and binary logistic regression. RESULTS: The study included 116 children (55.2% girls) with a mean age of 3.2 years, with obesity present in 62.1%, Exclusive breastfeeding in 72.4% with mean duration of 2.3 months, and age at introducing solids foods was 5.0 months. There was a difference for breastfeeding and complementary feeding by gender sex (P<.05). A PR=3.9 (95% CI: 1.49-6.34) was calculated for exclusive breastfeeding and risk of obesity. The model showed no association between these variables and obesity in children CONCLUSIONS: Exclusive breastfeeding of less than three months is associated with almost 4 more times in obese children. There was a difference in age of complementary feeding, duration of breastfeeding, and formula milk consumption time for obese and non-obese children. PMID- 26880167 TI - Effectiveness of Internet- and mobile-based psychological interventions for the prevention of mental disorders: a systematic review and meta-analysis protocol. AB - BACKGROUND: Despite progress in developing technologies for health promotion and disease treatment, mental disorders remain highly prevalent. In light of the associated personal and societal burden, primary prevention of new onset disorder can be seen as a primary challenge for health care systems and society. Internet- and mobile-based interventions (IMIs) are a promising approach to scale up preventive measures to a population level. The present protocol describes the rationale and design of a systematic review on the effectiveness of IMIs for the prevention of mental disorders. METHODS/DESIGN: A systematic literature search (MEDLINE, PsycINFO, CENTRAL) will be conducted. Keywords will target the topics "prevention", "mental disorders", and "Internet and mobile-based interventions". Studies eligible for inclusion will be retrieved, and data will be extracted and evaluated (design, population, outcomes, sample size, duration of intervention and follow-up, drop-out rate) by two independent researchers. Quality of evidence will be assessed, and results will be synthesized qualitatively and pooled meta analytically when outcome data are comparable in terms of endpoints, assessments, and target disorders. DISCUSSION: Prevention of mental disorders is one of the major emerging global health challenges. This review and meta-analysis will contribute to our understanding of the potential role for IMIs to help address this challenge. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026781. PMID- 26880170 TI - Alpha synuclein and crystallin expression in human lens in Parkinson's disease. PMID- 26880169 TI - Role of ITPA gene polymorphism in ribavirin-induced anemia and thrombocytopenia in Egyptian patients with chronic hepatitis C. AB - BACKGROUND: Ribavirin (RBV)-induced anemia is one of the major causes of dose reduction and discontinuation of therapy for chronic hepatitis C (CHC) patients. We investigated the role of inosine triphosphate pyrophosphatase (ITPA) single nucleotide polymorphism (SNP) (rs1127354) in predicting RBV-induced anemia and thrombocytopenia among Egyptian patients with CHC genotype 4 infection. METHODS: One hundred and twenty Egyptian patients with CHC genotype 4 who had received standard of care combination therapy were enrolled in this study. Single nucleotide polymorphism at ITPA (rs1127354) was genotyped by real-time detection polymerase chain reaction. RESULTS: Hb levels between CC and non-CC groups were significantly different at weeks 4, 8, and 12. Hemoglobin decline was significantly higher among CC patient than non-CC patients at week 4 and week 8 of treatment. The RBV dose reduction was higher in CC than non-CC group. Platelet decline was significantly lower in CC patients than non-CC patients at baseline, 4, 12 weeks only. CONCLUSION: Rs1127354 ITPA polymorphism was associated with RBV induced anemia and thrombocytopenia in Egyptian patients with hepatitis C virus genotype 4 infection. PMID- 26880168 TI - Gene expression profiling and DNA methylation analyses of CTCs. AB - A variety of molecular assays have been developed for CTCs detection and molecular characterization. Molecular assays are based on the nucleic acid analysis in CTCs and are based on total RNA isolation and subsequent mRNA quantification of specific genes, or isolation of genomic DNA that can be for DNA methylation studies and mutation analysis. This review is mainly focused on gene expression and methylation studies in CTCs in various types of cancer. PMID- 26880171 TI - Nanoscale optical interferometry with incoherent light. AB - Optical interferometry has empowered an impressive variety of biosensing and medical imaging techniques. A widely held assumption is that devices based on optical interferometry require coherent light to generate a precise optical signature in response to an analyte. Here we disprove that assumption. By directly embedding light emitters into subwavelength cavities of plasmonic interferometers, we demonstrate coherent generation of surface plasmons even when light with extremely low degrees of spatial and temporal coherence is employed. This surprising finding enables novel sensor designs with cheaper and smaller light sources, and consequently increases accessibility to a variety of analytes, such as biomarkers in physiological fluids, or even airborne nanoparticles. Furthermore, these nanosensors can now be arranged along open detection surfaces, and in dense arrays, accelerating the rate of parallel target screening used in drug discovery, among other high volume and high sensitivity applications. PMID- 26880172 TI - Applications of process improvement techniques to improve workflow in abdominal imaging. AB - Major changes in the management and funding of healthcare are underway that will markedly change the way radiology studies will be reimbursed. The result will be the need to deliver radiology services in a highly efficient manner while maintaining quality. The science of process improvement provides a practical approach to improve the processes utilized in radiology. This article will address in a step-by-step manner how to implement process improvement techniques to improve workflow in abdominal imaging. PMID- 26880173 TI - Effect of available intravenous access on accuracy and timeliness of epinephrine administration. AB - PURPOSE: To evaluate the effect of available intravenous (IV) access on the accuracy and timeliness of epinephrine administration during a surprise mock severe contrast reaction. METHODS: Informed consent was waived for this prospective randomized IRB-approved study. Radiology trainees with previous annual hands-on contrast reaction training (n = 46) were randomized to one of two surprise mock contrast reactions over a 23-month period: Group 1-severe laryngeal edema with IV access present (n = 27) or Group 2-severe laryngeal edema without IV access present (n = 19). Both intramuscular (IM, Epi-Pen((r))) and IV epinephrine were available in both scenarios. Time-to-treat and epinephrine administration error rates were compared by study group and by route of administration using two-tailed Student's t test or chi (2) test. Epinephrine administration errors were correlated with training experience using Pearson's correlation. RESULTS: Mean time to epinephrine administration was significantly faster for scenarios without IV access (Group 2: 35 +/- 16 s vs. Group 1: 62 +/- 49 s, p = 0.03), and for intramuscular administrations overall (IM: 42 +/- 34 s vs. IV: 98 +/- 46 s, p < 0.001). Epinephrine administration errors were common: (63% [17/27, Group 1] vs. 61% [11/18, Group 2], p = 1.00), had no relationship with time to most recent hands-on training (r = 0.24, p = 0.11), and were not predicted by year of post-graduate training (r = 0.04, p = 0.79). CONCLUSIONS: Lack of IV access is associated with a faster epinephrine administration time but no improvement in epinephrine administration error rate among radiology trainees responding to a surprise mock severe contrast reaction. Annual hands-on training appears to have little effect on epinephrine administration accuracy. PMID- 26880174 TI - Diagnostic value of strain elastography for differentiation between renal cell carcinoma and transitional cell carcinoma of kidney. AB - PURPOSE: The objective of our study was to prospectively evaluate the diagnostic performance of strain elastography for differentiation between renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs) of kidney. METHODS: A total of 99 consecutive patients who were referred to our hospital because of a newly diagnosed solid renal mass suspicious for malignancy on radiological screenings were evaluated with sonography, including strain elastography. Strain elastography was used to compare the stiffness of the renal masses and renal cortex. The ratio of strain in a renal mass and nearby renal cortex was defined as the strain index value. Mean strain index values for RCCs and TCCs were compared, and mean strain index values between histological subtypes of RCC were also compared. RESULTS: Although TCCs were smaller than RCCs (p < 0.001), there were no significant differences in gender distribution and mean age of the patients, and mean probe-tumor distance between RCC and TCC. The mean strain index value +/-SD for TCC (5.18 +/- 1.12) was significantly higher than the value for RCC (4.04 +/- 0.72; p < 0.001). Mean strain index value for papillary cell carcinomas (4.09 +/- 0.45) was slightly higher than that for clear cell carcinomas (3.85 +/- 0.78): however, the difference was not statistically significant (p = 0.51). CONCLUSIONS: Strain elastography can be used as a valuable imaging technique for preoperative differentiation between RCC and TCC of kidney. PMID- 26880175 TI - Reassessing medicare trends in diagnostic CT colonography after achieving CPT code category I status. AB - PURPOSE: Compare national trends in utilization and coverage of diagnostic (non screening) computed tomography colonography (CTC) in the Medicare population before and after achieving Current Procedural Terminology((r)) (CPT) Category I code status in 2010. METHODS: Claims by provider type and location for diagnostic CTC were identified between 2005 and 2013 using Medicare Physician Supplier Procedure Summary Master Files. Frequencies of billed and denied services were used to calculate denial rates for CTC and abdominal computed tomography (CT). PubMed search for articles with "CT colonography" in abstract or title during 1997-2013 was performed. Publications were recorded yearly and matched to CTC denial rates. RESULTS: Annual Medicare claims for diagnostic CTC increased 212% during 2005-2009 in Category III status and increased 27.4% during 2009-2013 after implementation of Category I codes. Claims for abdominal CT rose 13.4% over the same overall period. Denial rates decreased from 70% to 32.8% between 2005 and 2009, and fluctuated between 24.7 and 30.6% thereafter. Denial rates for abdominal CT remained constant (4.1%-4.6%). From 2005 to 2013, services grew most in the private office (1678-7293) and hospital outpatient (1644-6449) settings with radiologists performing 93.3% of CTC. 1037 CTC publications were identified which increased 3567% between 1997 (3) and 2008 (107), plateaued until 2010 (114) and declined thereafter (75 in 2013). CONCLUSIONS: Diagnostic CTC grew dramatically from 2005 to 2009, but slowed thereafter; even after achieving CPT Category I code status in 2010. Medicare denial rates declined during early years but later stabilized which paralleled a slowing in new peer-reviewed research. CTC continues to be performed predominately by radiologists in the outpatient setting. PMID- 26880176 TI - Influence of age, sex, body mass index, alcohol, and smoking on shear wave velocity (p-SWE) of the pancreas. AB - PURPOSE: A variety of elastographic techniques have been developed to facilitate the non-invasive assessment of tissue properties. The goal of the study was to examine the influence of gender, age, BMI, alcohol consumption, and smoking in healthy volunteers. METHODS: Of the 263 participants who met all the study inclusion criteria, 234 had successful measurements. The examination was performed with the Siemens Acuson S3000 (Siemens Healthcare, Erlangen, Germany), using the 6C1 curved array transducer with the virtual touch tissue quantification (VTQ) method. RESULTS: The values determined with the curved array in the head of the pancreas were 1.44 +/- 0.39 m/s for women and 1.19 +/- 0.29 m/s for men; in the body, the results were 1.49 +/- 0.37 m/s for women and 1.26 +/- 0.30 m/s for men; in the tail, the corresponding values were 1.29 +/- 0.36 m/s for women and 1.05 +/- 0.30 m/s for men. Comparison of gender showed that men have significantly lower mean values than women. There were significantly higher values in all parts of the organ with the increasing age of the participants (p < 0.0001). For BMI, there was a significant correlation with the values only when considering the BMI in continuous form. Alcohol consumption and smoking did not have any significant effects. CONCLUSIONS: ARFI-VTQ is qualified for use on pancreatic tissue. Further studies are required to examine the influence of other factors in larger populations. PMID- 26880177 TI - Microwave ablation for liver tumors. AB - Surveillance programs and widespread use of medical imaging have increased the detection of hepatic tumors. When feasible, surgical resection is widely accepted as the curative treatment of choice, but surgical morbidity and mortality has spurred the development of minimally invasive ablative technologies over the last 2 decades. Microwave ablation has emerged as a promising thermal ablation modality with improving oncologic efficacy due to technical improvements and image guidance strategies. This article provides an overview of microwave application in liver tumors, and we discuss currently available equipment, clinical efficacy, and safety and provide comparisons with other commonly used therapies. This article also introduces advanced ablative techniques and combination therapies that may help achieve precise ablation and further enhance the efficacy of microwave ablation. PMID- 26880178 TI - Kidney disease and aging: A reciprocal relation. AB - Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process. PMID- 26880179 TI - EMG Functional tasks recordings determines frailty phenotypes in males and females. AB - BACKGROUND: Identification of frailty is essential to understanding and mitigating age-related physical impairments. Previous studies have indicated that frailty phenotype can be identified through electromyography (EMG) when collected over the course of an 8-h day. However, long duration recordings challenge both the clinician and the older adults but activities of daily living that are most sensitive to changes in frailty status are currently unknown. The purpose of this study was to determine if muscle activity recorded during specific task, or groups of tasks, could be used to correctly classify middle-aged, non-frail, pre frail, and frail older adult pheonotypes. METHODS: Fifteen middle-aged (49 +/- 5 years) and 76 older adults (77 +/- 8 years) participated. Older adults were categorized as non-frail (n = 49), pre-frail (n = 20), or frail (n = 7) using self-selected normal gait speed and a modified frailty index score. Bursts and gaps in EMG of the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris were measured bilaterally during nine different functional tasks. RESULTS: Relatively high levels of success for frailty group classification (near 90%) can be achieved from EMG. Bursts were more frequent and gaps fewer in frail compared with middle-aged and non-frail adults. The numbers of gaps and muscle quiescence in the upper limbs were particularly important. Changes in muscle activity offer predictive value in identifying frailty phenotype. Completing functional tasks (rising from the floor, toilet and chair) while undergoing EMG assessment can contribute to the identification of differences in frailty phenotype among older adults. PMID- 26880180 TI - Fluorine-directed 1,2-trans glycosylation of rare sugars. AB - To reconcile the urgent need to access well defined beta-configured 2,6-di deoxypyranose analogues for chemical biology, with the intrinsic alpha selectivity of the native system, the directing role of fluorine at C2 has been explored. Localised partial charge inversion (C-H(delta+)-> C-F(delta-)) elicits a reversal of the substrate-based alpha-stereoselectivity, irrespective of the protecting group electronics. PMID- 26880181 TI - The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan: a systematic review. AB - Gilles de la Tourette syndrome (GTS) and other chronic tic disorders are neurodevelopmental conditions characterized by the presence of tics and associated behavioral problems. Whilst converging evidence indicates that these conditions can affect patients' quality of life (QoL), the extent of this impairment across the lifespan is not well understood. We conducted a systematic literature review of published QoL studies in GTS and other chronic tic disorders to comprehensively assess the effects of these conditions on QoL in different age groups. We found that QoL can be perceived differently by child and adult patients, especially with regard to the reciprocal contributions of tics and behavioral problems to the different domains of QoL. Specifically, QoL profiles in children often reflect the impact of co-morbid attention-deficit and hyperactivity symptoms, which tend to improve with age, whereas adults' perception of QoL seems to be more strongly affected by the presence of depression and anxiety. Management strategies should take into account differences in age-related QoL needs between children and adults with GTS or other chronic tic disorders. PMID- 26880184 TI - Effect of Electrolyte Concentration on the Stern Layer Thickness at a Charged Interface. AB - The chemistry and physics of charged interfaces is regulated by the structure of the electrical double layer (EDL). Herein we quantify the average thickness of the Stern layer at the silica (SiO2 ) nanoparticle/aqueous electrolyte interface as a function of NaCl concentration following direct measurement of the nanoparticles' surface potential by X-ray photoelectron spectroscopy (XPS). We find the Stern layer compresses (becomes thinner) as the electrolyte concentration is increased. This finding provides a simple and intuitive picture of the EDL that explains the concurrent increase in surface charge density, but decrease in surface and zeta potentials, as the electrolyte concentration is increased. PMID- 26880183 TI - Hidden Inflammatory Molecular Signatures in Graft Kidney Biopsies: Silent Markers of Graft Fate? PMID- 26880182 TI - Folate supplementation in people with sickle cell disease. AB - BACKGROUND: Sickle cell disease is a group of disorders that affects haemoglobin, which causes distorted sickle- or crescent-shaped red blood cells. It is characterized by anaemia, increased susceptibility to infections and episodes of pain. The disease is acquired by inheriting abnormal genes from both parents, the combination giving rise to different forms of the disease. Due to increased erythropoiesis in people with sickle cell disease, it is hypothesized that they are at an increased risk for folate deficiency. For this reason, children and adults with sickle cell disease, particularly those with sickle cell anaemia, commonly take 1 mg of folic acid orally every day on the premise that this will replace depleted folate stores and reduce the symptoms of anaemia. It is thus important to evaluate the role of folate supplementation in treating sickle cell disease. OBJECTIVES: To analyse the efficacy and possible adverse effects of folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also conducted additional searches in both electronic databases and clinical trial registries.Date of last search: 07 December 2015. SELECTION CRITERIA: Randomised, placebo-controlled trials of folate supplementation for sickle cell disease. DATA COLLECTION AND ANALYSIS: Four review authors assessed the eligibility and risk of bias of the included trials and extracted and analysed the data included in the review. We used the standard Cochrane-defined methodological procedures. MAIN RESULTS: One trial, undertaken in 1983, was eligible for inclusion in the review. This was a double-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with sickle cell disease. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children).Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 ug/l and values below 5 ug/l. In the folic acid group, values above 18 ug/l were observed in 33 of 41 (81 %) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 ug/l, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year. It is important to note that none of the raw data for the outcomes listed above were available for analysis.The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio 0.99 (95% confidence interval 0.85 to 1.15); major infections, risk ratio 0.89 (95% confidence interval 0.47 to 1.66); dactylitis, risk ratio 0.67 (95% confidence interval 0.35 to 1.27); acute splenic sequestration, risk ratio 1.07 (95% confidence interval 0.44 to 2.57); or episodes of pain, risk ratio 1.16 (95% confidence interval 0.70 to 1.92). However, the investigators reported a higher proportion of repeat dactylitis episodes in the placebo group, with two or more attacks occurring in 10 of 56 participants compared to two of 59 in the folic acid group (P < 0.05).Growth, determined by height-for-age and weight-for-age, as well as height and growth velocity, was measured in 103 of the 115 participants (90%), for which raw data were not available. The investigators reported no significant differences in growth between the two groups.The trial had a high risk of bias with regards to random sequence generation and incomplete outcome data. There was an unclear risk of bias in relation to allocation concealment, outcome assessment, and selective reporting. Finally, There was a low risk of bias with regards to blinding of participants and personnel. Overall the quality of the evidence in the review was low.There were no trials identified for other eligible comparisons, namely: folate supplementation (fortified foods and physical supplementation with tablets) versus placebo; folate supplementation (naturally occurring in diet) versus placebo; folate supplementation (fortified foods and physical supplementation with tablets) versus folate supplementation (naturally occurring in diet). AUTHORS' CONCLUSIONS: One doubIe-blind, placebo-controlled triaI on folic acid supplementation in children with sickle cell disease was included in the review. Overall, the trial presented mixed evidence on the review's outcomes. No trials in adults were identified. With the limited evidence provided, we conclude that, while it is possible that folic acid supplementation may increase serum folate levels, the effect of supplementation on anaemia and any symptoms of anaemia remains unclear.Further trials may add evidence regarding the efficacy of folate supplementation. Future trials should assess clinical outcomes such as folate concentration, haemoglobin concentration, adverse effects and benefits of the intervention, especially with regards to sickle cell disease-related morbidity. Trials should include people with sickle cell disease of all ages and both sexes, in any setting. To investigate the effects of folate supplementation, trials should recruit more participants and be of longer duration, with long-term follow up, than the trial currently included in this review. PMID- 26880185 TI - Interface Structure of MoO3 on Organic Semiconductors. AB - We have systematically studied interface structure formed by vapor-phase deposition of typical transition metal oxide MoO3 on organic semiconductors. Eight organic hole transport materials have been used in this study. Ultraviolet photoelectron spectroscopy and X-ray photoelectron spectroscopy are used to measure the evolution of the physical, chemical and electronic structure of the interfaces at various stages of MoO3 deposition on these organic semiconductor surfaces. For the interface physical structure, it is found that MoO3 diffuses into the underlying organic layer, exhibiting a trend of increasing diffusion with decreasing molecular molar mass. For the interface chemical structure, new carbon and molybdenum core-level states are observed, as a result of interfacial electron transfer from organic semiconductor to MoO3. For the interface electronic structure, energy level alignment is observed in agreement with the universal energy level alignment rule of molecules on metal oxides, despite deposition order inversion. PMID- 26880186 TI - Government promises L1bn a year more to "transform" mental health in England. PMID- 26880189 TI - Corrigendum: Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2. PMID- 26880187 TI - Characterization of hepatitis E virus infection in tree shrew (Tupaia belangeri chinensis). AB - BACKGROUND: Hepatitis E virus (HEV) is a major cause of hepatitis in developing countries and poses a threat to public health worldwide. Tree shrew (Tupaia belangeri chinensis) is a useful animal model in studies on hepatitis viruses, such as hepatitis B and C viruses. However, the use of this animal model for HEV research is yet to be developed. METHODS: Tree shrews were intravenously (IV) injected with swine genotype 4 HEV or infected by contact-exposure to IV infected tree shrews. RT-nPCR was performed to detect HEV RNA in the feces, tissues, and blood. HEV capsid protein in the different tissues was detected by Western blot and estimated by quantitative RT-PCR. Anti-HEV antibodies were determined by ELISA. Liver damages were evaluated by histopathologic examination and analysis of liver-specific enzymes activities. RESULTS: Both negative and positive strands of HEV RNA were detected in the feces of the HEV-infected or contact-exposed tree shrews 3-4 days post-inoculation. HEV RNA was detectable in the liver, spleen, kidneys, and bile. Virusemia developed in all the HEV-infected tree shrews. HEV capsid protein was expressed in the liver, spleen, and kidneys. The histological examination and analysis of liver-specific enzymes activities showed that HEV caused acute liver lesions in the tree shrews. Meanwhile, the infected tree shrews showed positive IgG and IgM antibodies. CONCLUSIONS: Tree shrews are susceptible to HEV and may be useful animal models for HEV experimental infection studies on pathogenesis or preclinical drug development. PMID- 26880188 TI - Precision multidimensional assay for high-throughput microRNA drug discovery. AB - Development of drug discovery assays that combine high content with throughput is challenging. Information-processing gene networks can address this challenge by integrating multiple potential targets of drug candidates' activities into a small number of informative readouts, reporting simultaneously on specific and non-specific effects. Here we show a family of networks implementing this concept in a cell-based drug discovery assay for miRNA drug targets. The networks comprise multiple modules reporting on specific effects towards an intended miRNA target, together with non-specific effects on gene expression, off-target miRNAs and RNA interference pathway. We validate the assays using known perturbations of on- and off-target miRNAs, and evaluate an ~700 compound library in an automated screen with a follow-up on specific and non-specific hits. We further customize and validate assays for additional drug targets and non-specific inputs. Our study offers a novel framework for precision drug discovery assays applicable to diverse target families. PMID- 26880190 TI - The Effect of a Workplace-Based Early Intervention Program on Work-Related Musculoskeletal Compensation Outcomes at a Poultry Meat Processing Plant. AB - Introduction The aim of this study is to determine whether a workplace-based early intervention injury prevention program reduces work-related musculoskeletal compensation outcomes in poultry meat processing workers. Methods A poultry meatworks in Queensland, Australia implemented an onsite early intervention which included immediate reporting and triage, reassurance, multidisciplinary participatory consultation, workplace modifica tion and onsite physiotherapy. Secondary pre-post analyses of the meatworks' compensation data over 4 years were performed, with the intervention commencing 2 years into the study period. Outcome measures included rate of claims, costs per claim and work days absent at an individual claim level. Where possible, similar analyses were performed on data for Queensland's poultry meat processing industry (excluding the meatworks used in this study). Results At the intervention meatworks, in the post intervention period an 18 % reduction in claims per 1 million working hours (p = 0.017) was observed. Generalized linear modelling revealed a significant reduction in average costs per claim of $831 (OR 0.74; 95 % CI 0.59-0.93; p = 0.009). Median days absent was reduced by 37 % (p = 0.024). For the poultry meat processing industry over the same period, generalized linear modelling revealed no significant change in average costs per claim (OR 1.02; 95 % CI 0.76-1.36; p = 0.91). Median days absent was unchanged (p = 0.93). Conclusion The introduction of an onsite, workplace-based early intervention injury prevention program demonstrated positive effects on compensation outcomes for work-related musculoskeletal disorders in poultry meat processing workers. Prospective studies are needed to confirm the findings of the present study. PMID- 26880192 TI - Selection against recombinant hybrids maintains reproductive isolation in hybridizing Populus species despite F1 fertility and recurrent gene flow. AB - Natural hybrid zones have proven to be precious tools for understanding the origin and maintenance of reproductive isolation (RI) and therefore species. Most available genomic studies of hybrid zones using whole- or partial-genome resequencing approaches have focused on comparisons of the parental source populations involved in genome admixture, rather than exploring fine-scale patterns of chromosomal ancestry across the full admixture gradient present between hybridizing species. We have studied three well-known European 'replicate' hybrid zones of Populus alba and P. tremula, two widespread, ecologically divergent forest trees, using up to 432 505 single-nucleotide polymorphisms (SNPs) from restriction site-associated DNA (RAD) sequencing. Estimates of fine-scale chromosomal ancestry, genomic divergence and differentiation across all 19 poplar chromosomes revealed strikingly contrasting results, including an unexpected preponderance of F1 hybrids in the centre of genomic clines on the one hand, and genomically localized, spatially variable shared variants consistent with ancient introgression between the parental species on the other. Genetic ancestry had a significant effect on survivorship of hybrid seedlings in a common garden trial, pointing to selection against early generation recombinants. Our results indicate a role for selection against recombinant genotypes in maintaining RI in the face of apparent F1 fertility, consistent with the intragenomic 'coadaptation' model of barriers to introgression upon secondary contact. Whole-genome resequencing of hybridizing populations will clarify the roles of specific genetic pathways in RI between these model forest trees and may reveal which loci are affected most strongly by its cyclic breakdown. PMID- 26880193 TI - Selecting stage ypT0-1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ sparing management. AB - AIM: Local excision or a wait-and-see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0-1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ-sparing management. This study was to establish a scoring system to select stage ypT0-1N0 for LARC following preoperative CRT. METHOD: Between 2009 and 2014, 262 patients with middle and low LARC were treated with CRT and radical surgery. Clinicopathological data which were found to be significantly associated with GR were incorporated into a scoring system. RESULTS: Fifty-seven (21.8%) patients were GR with stage ypT0-1N0 in the operative specimen. Multivariate analyses indicated that a low level of pretreatment carcinoembryonic antigen (CEA) and post-treatment CEA <2.55 ng/ml (P = 0.008 and P = 0.009 respectively) and long axis diameter of residual tumours (P = 0.006) were independently associated with stage ypT0-1N0. The three factors were incorporated into a scoring system. Using receiver operating characteristic curve analysis, we determined a cutoff value of -0.3 for scores, at which the system's sensitivity was 71.9% and specificity 73.1%. When applied to testing samples, the sensitivity was 74.1% and specificity 76.2%. CONCLUSION: We demonstrated that low levels of pretreatment and post treatment CEA and the long-axis diameter of residual tumours were associated with stage ypT0-1N0 for LARC after CRT. Therefore, the three-factor scoring system may be used to select potential candidates for organ-sparing management. PMID- 26880191 TI - Fugong virus, a novel hantavirus harbored by the small oriental vole (Eothenomys eleusis) in China. AB - BACKGROUND: Rodents are natural reservoirs of hantaviruses, which cause two disease types: hemorrhagic fever with renal syndrome in Eurasia and hantavirus pulmonary syndrome in North America. Hantaviruses related human cases have been observed throughout Asia, Europe, Africa, and North America. To date, 23 distinct species of hantaviruses, hosted by reservoir, have been identified. However, the diversity and number of hantaviruses are likely underestimated in China, and hantavirus species that cause disease in many regions, including Yunnan province, are unknown. RESULTS: In August 2012, we collected tissue samples from 189 captured animals, including 15 species belonging to 10 genera, 5 families, and 4 orders in Fugong county, Yunnan province, China. Seven species were positive for hantavirus: Eothenomys eleusis (42/94), Apodemus peninsulae (3/25), Niviventer eha (3/27), Cryptotis montivaga (2/8), Anourosorex squamipes (1/1), Sorex araneus (1/1), and Mustela sibirica (1/2). We characterized one full-length genomic sequence of the virus (named fugong virus, FUGV) from a small oriental vole (Eothenomys eleusis). The full-length sequences of the small, medium, and large segments of FUGV were 1813, 3630, and 6531 nt, respectively. FUGV was most closely related to hantavirus LX309, a previously reported species detected in the red-backed vole in Luxi county, Yunnan province, China. However, the amino acid sequences of nucleocapsid (N), glycoprotein (G), and large protein (L) were highly divergent from those of Hantavirus LX309, with amino acid differences of 11.2, 15.3, and 12.7 %, respectively. In phylogenetic trees, FUGV clustered in the lineage corresponding to hantaviruses carried by rodents in the subfamily Arvicolinae. CONCLUSIONS: High prevalence of hantavirus infection in small mammals was found in Fugong county, Yunnan province, China. A novel hantavirus species FUGV was identified from the small oriental vole. This virus is phylogenetic clustering with another hantavirus LX309, but shows highly genomic divergence. PMID- 26880194 TI - Diagnosis and prognosis of neutrophil gelatinase-associated lipocalin for acute kidney injury with sepsis: a systematic review and meta-analysis. AB - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early biomarker for prediction of acute kidney injury (AKI). However, the utility of NGAL to predict the occurrence of AKI in septic patients remains controversial. We performed a systematic review and meta-analysis to evaluate the evidence on diagnosis of sepsis AKI and the prediction of other clinical outcomes. METHOD: The MEDLINE, EMBASE, Cochrane Library, Wanfang, and CNKI databases were systematically searched up to August 19, 2015. Quality assessment was applied by using the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tool. The diagnostic performance of NGAL for the prediction of AKI in sepsis was evaluated using pooled estimates of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio (DOR), as well as summary receiver operating characteristic curves (SROC). RESULTS: Fifteen studies with a total of 1,478 patients were included in the meta-analysis. For plasma NGAL, the pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.83 (95% CI: 0.77 - 0.88) and 0.57 (95% CI: 0.54 - 0.61), respectively. The pooled positive likelihood ratio (PLR) was 3.10 (95% CI: 1.57 - 6.11) and the pooled negative likelihood ratio (NLR) was 0.24 (95% CI: 0.13 - 0.43). The pooled DOR was 14.72 (95% CI: 6.55 - 33.10) using a random effects model. The area under the curve (AUC) for SROC to summarize diagnostic accuracy was 0.86. For urine NGAL, the pooled sensitivity, specificity, PLR, NLR, DOR, and AUC values were 0.80 (95% CI: 0.77 - 0.83), 0.80 (95% CI: 0.77 - 0.83), 4.42 (95% CI: 2.84 - 6.89), 0.21 (95% CI: 0.13 - 0.35), 24.20 (95% CI: 9.92 - 59.05) and 0.90, respectively. Significant heterogeneity was explored as a potential source. There was no notable publication bias observed across the eligible studies. NGAL for prediction of renal replacement therapy (RRT) and mortality associated with AKI in septic patients were also evaluated. CONCLUSION: To a certain extent, NGAL is not only an effective predictive factor for AKI in the process of sepsis, but also shows potential predictive value for RRT and mortality. However, future trials are needed to clarify this controversial issue. PMID- 26880196 TI - Thermal and Environmental Stability of Semi-Transparent Perovskite Solar Cells for Tandems Enabled by a Solution-Processed Nanoparticle Buffer Layer and Sputtered ITO Electrode. AB - A sputtered oxide layer enabled by a solution-processed oxide nanoparticle buffer layer to protect underlying layers is used to make semi-transparent perovskite solar cells. Single-junction semi-transparent cells are 12.3% efficient, and mechanically stacked tandems on silicon solar cells are 18.0% efficient. The semi transparent perovskite solar cell has a T 80 lifetime of 124 h when operated at the maximum power point at 100 degrees C without additional sealing in ambient atmosphere under visible illumination. PMID- 26880195 TI - Does local ambient temperature impact children's blood pressure? A Chinese National Survey. AB - BACKGROUND: Several studies demonstrated a short-term association between ambient temperature and blood pressure. However, few studies have assessed the long-term effect of ambient temperature on children's blood pressure. The present study aimed to investigate the association between long-term exposure to local ambient temperature and children's blood pressure in China. METHODS: We analyzed the systolic (SBP) and diastolic blood pressure (DBP) data of 71,763 children from 2010 Chinese National Survey on Students' Construction and Health (CHNSCH), and local annual average ambient temperature, relative humidity, air pollutants data from China Meteorological Administration and Ministry of Environment Protection of China. We used generalized additive model (GAM) with non-linear function to examine the effects of ambient temperature on children's blood pressure. RESULTS: The results showed that decrease of ambient temperature was negatively associated with increase of both SBP and DBP in Chinese children while adjusting for individual characteristics, socioeconomic conditions, air pollutants and relative humidity. The largest alteration of SBP related to the temperature difference was observed from 20.4 to 9.6 degrees C, with 9.0 mmHg (95 % CI: 8.4, 9.5) increase in SBP, while the largest alteration of DBP was observed from 21.7 to 10.2 degrees C, with 6.1 mmHg (95 % CI: 5.6, 6.6) increase in DBP. However, when temperature below 9.6 and 10.2 degrees C, SBP and DBP started to decrease, which might be caused by the use of heating system in the extreme cold areas. CONCLUSIONS: Public health policy should be improved for protecting children's cardiovascular health from adverse effects of low temperature. Development of heating system in moderate cold area might be a good solution. PMID- 26880197 TI - Elisabetta Dejana: Probing the vagaries of vessels. PMID- 26880198 TI - Breaking down to build up: Neuroligin's C-terminal domain strengthens the synapse. AB - The mechanisms by which neuroligin adhesion molecules modulate synaptic plasticity remain unclear. In this issue, Liu et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201509023) demonstrate that neuroligin 1 promotes actin assembly associated with synaptic strengthening independent of adhesion, suggesting additional ways for neuroligins to contribute to neuronal development and disease pathology. PMID- 26880199 TI - MRN, CtIP, and BRCA1 mediate repair of topoisomerase II-DNA adducts. AB - Repair of DNA double-strand breaks (DSBs) with complex ends poses a special challenge, as additional processing is required before DNA ligation. For example, protein-DNA adducts must be removed to allow repair by either nonhomologous end joining or homology-directed repair. Here, we investigated the processing of topoisomerase II (Top2)-DNA adducts induced by treatment with the chemotherapeutic agent etoposide. Through biochemical analysis in Xenopus laevis egg extracts, we establish that the MRN (Mre11, Rad50, and Nbs1) complex, CtIP, and BRCA1 are required for both the removal of Top2-DNA adducts and the subsequent resection of Top2-adducted DSB ends. Moreover, the interaction between CtIP and BRCA1, although dispensable for resection of endonuclease-generated DSB ends, is required for resection of Top2-adducted DSBs, as well as for cellular resistance to etoposide during genomic DNA replication. PMID- 26880200 TI - Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway. AB - Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. PMID- 26880201 TI - Biophysical changes reduce energetic demand in growth factor-deprived lymphocytes. AB - Cytokine regulation of lymphocyte growth and proliferation is essential for matching nutrient consumption with cell state. Here, we examine how cellular biophysical changes that occur immediately after growth factor depletion promote adaptation to reduced nutrient uptake. After growth factor withdrawal, nutrient uptake decreases, leading to apoptosis. Bcl-xL expression prevents cell death, with autophagy facilitating long-term cell survival. However, autophagy induction is slow relative to the reduction of nutrient uptake, suggesting that cells must engage additional adaptive mechanisms to respond initially to growth factor depletion. We describe an acute biophysical response to growth factor withdrawal, characterized by a simultaneous decrease in cell volume and increase in cell density, which occurs before autophagy initiation and is observed in both FL5.12 Bcl-xL cells depleted of IL-3 and primary CD8(+) T cells depleted of IL-2 that are differentiating toward memory cells. The response reduces cell surface area to minimize energy expenditure while conserving biomass, suggesting that the biophysical properties of cells can be regulated to promote survival under conditions of nutrient stress. PMID- 26880202 TI - Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization. AB - Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin-mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function. PMID- 26880205 TI - Mechanisms of germ line genome instability. AB - During meiosis, numerous DNA double-strand breaks (DSBs) are formed as part of the normal developmental program. This seemingly destructive behavior is necessary for successful meiosis, since repair of the DSBs through homologous recombination (HR) helps to produce physical links between the homologous chromosomes essential for correct chromosome segregation later in meiosis. However, DSB formation at such a massive scale also introduces opportunities to generate gross chromosomal rearrangements. In this review, we explore ways in which meiotic DSBs can result in such genomic alterations. PMID- 26880203 TI - Ataxin-3 phosphorylation decreases neuronal defects in spinocerebellar ataxia type 3 models. AB - Different neurodegenerative diseases are caused by aberrant elongation of repeated glutamine sequences normally found in particular human proteins. Although the proteins involved are ubiquitously distributed in human tissues, toxicity targets only defined neuronal populations. Changes caused by an expanded polyglutamine protein are possibly influenced by endogenous cellular mechanisms, which may be harnessed to produce neuroprotection. Here, we show that ataxin-3, the protein involved in spinocerebellar ataxia type 3, also known as Machado Joseph disease, causes dendritic and synapse loss in cultured neurons when expanded. We report that S12 of ataxin-3 is phosphorylated in neurons and that mutating this residue so as to mimic a constitutive phosphorylated state counters the neuromorphologic defects observed. In rats stereotaxically injected with expanded ataxin-3-encoding lentiviral vectors, mutation of serine 12 reduces aggregation, neuronal loss, and synapse loss. Our results suggest that S12 plays a role in the pathogenic pathways mediated by polyglutamine-expanded ataxin-3 and that phosphorylation of this residue protects against toxicity. PMID- 26880206 TI - Development and Psychometric Testing of the Humanistic Nurse-Patient Scale. AB - Quality of life and well-being of older patients in chronic care facilities is often determined by their relationships with nurses. The authors developed and tested a scale to assess patients' views of what matters most when relating to nurses. Based on the humanistic nursing theory by Paterson and Zderad (1988), 69 items were created and tested with a sample of 40 patients, resulting in refinement of a scale with 24 items. This scale was factor analysed on responses from 249 patients residing in five facilities in Ontario, Canada. The Humanistic Relationship Importance Scale demonstrated strong internal consistency, stability, and reliability with a five-factor solution (alpha = .87). Construct validity was supported through factual identification. This scale is a valid measure of patients' perspectives of a nurse-patient relationship in chronic care and can be used to measure health professionals' relationships with their older patients and evaluate interventions to enhance relational care. PMID- 26880207 TI - The Elsevier trophoblast research award lecture: Impacts of placental growth factor and preeclampsia on brain development, behaviour, and cognition. AB - Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf-/- brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s. PMID- 26880209 TI - In Memoriam. Lori L. Altshuler M.D. PMID- 26880208 TI - Lithium treatment and cancer incidence in bipolar disorder. AB - OBJECTIVES: To investigate whether there is an increased risk of cancer associated with lithium treatment in patients with bipolar disorder compared to the general population. METHODS: A nationwide Swedish register study of incidence rate ratios (IRRs) of total cancer and site-specific cancer in the 50-84-year age range was carried out in patients with bipolar disorder (n = 5,442) with and without lithium treatment from July 2005 to December 2009 compared to the general population using linked information from The Swedish Cancer Register, The National Patient Register, and The Drug Prescription Register. RESULTS: The overall cancer risk was not increased in patients with bipolar disorder. There was no difference in risk of unspecified cancer, neither in patients with lithium treatment compared to the general population [IRR = 1.04, 95% confidence interval (CI): 0.89-1.23] nor in patients with bipolar disorder without lithium treatment compared to the general population (IRR = 1.03, 95% CI: 0.89-1.19). The cancer risk was significantly increased in patients with bipolar disorder without lithium treatment in the digestive organs (IRR = 1.47, 95% CI: 1.12-1.93), in the respiratory system and intrathoracic organs (IRR = 1.72, 95% CI: 1.11-2.66), and in the endocrine glands and related structures (IRR = 2.60, 95% CI: 1.24-5.47), but in patients with bipolar disorder with lithium treatment, there was no significantly increased cancer risk compared to the general population. CONCLUSIONS: Bipolar disorder was not associated with increased cancer incidence and neither was lithium treatment in these patients. Specifically, there was an increased risk of respiratory, gastrointestinal, and endocrine cancer in patients with bipolar disorder without lithium treatment. PMID- 26880204 TI - Effect of TGF-beta1 on the Migration and Recruitment of Mesenchymal Stem Cells after Vascular Balloon Injury: Involvement of Matrix Metalloproteinase-14. AB - Restenosis or occlusion after vascular procedures is ascribed to intimal hyperplasia. Transforming growth factor (TGF)-beta1 is involved in recruitment of mesenchymal stem cells (MSCs) following arterial injury, and its release from latent TGF-binding protein by matrix metalloproteinase (MMP)-14-induced proteolysis contributes to neointima formation. However, the relationship between MMP-14 and TGF-beta1 activation in restenosis is unknown. This study investigated the relationship using a rat model of balloon-induced injury. Rats were assigned to vehicle-, SB431542 (SB)-, or recombinant human (rh)TGF-beta1-treated groups and examined at various time points after balloon-induced injury for expression of TGF-beta1/Smad signalling pathway components, MMP-14 and MSCs markers including Nestin, CD29, and Sca1(+)CD29(+)CD11b/c(-)CD45(-). Intimal hyperplasia was reduced in SB- and rhTGF-beta1-treated rats. The expression of TGF-beta1, TGF beta1RI, and Smad2/3 was decreased, but the levels of phosphorylated Smad2/3 were higher in SB-treated rats than vehicle-treated after 7 days to 14 days. rhTGF beta1 administration decreased the expression of TGF-beta1/Smad pathway proteins, except for TGF-beta1RI. Nestin and CD29 expression and the number of Sca1(+)CD29(+)CD11b(-)CD45(-) cells were reduced, whereas MMP-14 expression was increased after SB431542 and rhTGF-beta1 administration. These results suggest that TGF-beta1/Smad signalling and MMP-14 act to recruit MSCs which differentiate to vascular smooth muscle cells and mesenchymal-like cells that participate in arterial repair/remodelling. PMID- 26880210 TI - Total Synthesis of (-)-Chromodorolide B. AB - The first total synthesis of a chromodorolide diterpenoid is described. The synthesis features a bimolecular radical addition/cyclization/fragmentation cascade that unites butenolide and trans-hydrindane fragments while fashioning two C-C bonds and stereoselectively forming three of the ten contiguous stereocenters of chromodorolide B. PMID- 26880211 TI - Conformational analysis and NMR assignments of dibenzoxocins from Sappan Lignum. PMID- 26880212 TI - Synthesis of Bis(pentafluoroethyl)germanes. AB - The chemistry of bis(pentafluoroethyl)germanes (C2F5)2 GeX2 is presented. The synthesis of such species requires Br2 GePh2 , wherein the phenyl substituents function as suitable protecting groups. After treatment with two equivalents of LiC2 F5, (C2F5)2 GePh2 is produced. The replacement of the phenyl rings is smoothly effected by gaseous HBr or HCl in the presence of a Lewis acidic catalyst. The trigermoxane [(C2F5)2 GeO]3 results from the reaction of (C2F5)2 GeBr2 with Ag2 CO3. Its crystalline 1,10-phenanthroline adduct was fully characterised by X-ray diffraction. The combination of (C2F5)2 GeBr2 with Bu3 SnH gave rise to the formation of (C2F5)2 GeH2 . PMID- 26880214 TI - Evaluation of Safety of Iron-Fortified Soybean Sprouts, a Potential Component of Functional Food, in Rat. AB - Ferritin-iron is currently considered as one of the most promising iron forms to prevent iron deficiency anaemia. We found that the cultivation of soybean seeds in a solution of ferrous sulfate results in material with extremely high iron content - 560.6 mg Fe/100 g of dry matter, while ferritin iron content was 420.5 mg/100 g dry matter. To assess the potential adverse effects of a preparation containing such a high concentration of iron, male and female Wistar rats were exposed via diet to 10, 30, 60 g soybean sprouts powder/kg feed for 90 days. There were no differences in final body weight and mean food consumption between controls and rats administered sprouts. No statistically significant differences in haematology and clinical chemistry parameters were found between controls and treated rats. Microscopic examination of 22 tissues did not reveal any pathology due to soybean sprouts intake. Long term administration of the test material did not cause oxidative damage to DNA and protein in the liver as evidenced by the unchanged basal levels of DNA damage as well as carbonyl groups content. Lipid peroxidation was slightly increased only in females. The activity of several antioxidant enzymes: superoxide dismutase, glutathione peroxidase and glutathione S-transferase was increased, which substantially enhanced the antioxidant status in the liver from the rats treated with soybean sprouts. Hence, the material tested can be recommended as a component of food supplements for individuals with iron deficiency anaemia and inflammatory bowel diseases. PMID- 26880213 TI - Impact of selenium supplementation on fish antiviral responses: a whole transcriptomic analysis in rainbow trout (Oncorhynchus mykiss) fed supranutritional levels of Sel-Plex(r). AB - BACKGROUND: Selenium (Se) is required for the synthesis of proteins (selenoproteins) with essential biological functions. Selenoproteins have a crucial role in the maintenance of cellular redox homeostasis in nearly all tissues, and are also involved in thyroid hormone metabolism, inflammation and immunity. Several immune processes rely on Se status and can be compromised if this element is present below the required level. Previous work has supported the notion that when Se is delivered at levels above those deemed to be the minimal required but below toxic concentrations it can have a boosting effect on the organism's immune response. Based on this concept Se-enriched supplements may represent a valuable resource for functional feeds in animal farming, including aquaculture. RESULTS: In this study we tested the effects of Se supplemented as Sel-Plex during an immune challenge induced by polyinosinic:polycytidylic acid (poly(I:C)), a pathogen-associated molecular pattern (PAMP) that mimics viral infection. Trout were fed two diets enriched with 1 or 4 mg Se Kg(-1) of feed (dry weight) by Sel-Plex addition and a commercial formulation as control. The whole trout transcriptomic response was investigated by microarray and gene ontology analysis, the latter carried out to highlight the biological processes that were influenced by Sel-Plex supplementation in the head kidney (HK) and liver, the main immune and metabolic organs in fish. Overall, Sel-Plex enrichment up to 4 mg Se Kg(-1) induced an important response in the trout HK, eliciting an up-regulation of several genes involved in pathways connected with hematopoiesis and immunity. In contrast, a more constrained response was seen in the liver, with lipid metabolism being the main pathway altered by Se supplementation. Upon stimulation with poly(I:C), supplementation of 4 mg Se Kg(-1) increased the expression of principal mediators of the antiviral defences, especially IFN gamma, and down-stream molecules involved in the cell-mediated immune response. CONCLUSIONS: Supplementation of diets with 4 mg Se Kg(-1) using Sel-Plex remarkably improved the fish response to viral PAMP stimulation. Sel-Plex, being a highly bioavailable supplement of organic Se, might represent a suitable option for supplementation of fish feeds, to achieve the final aim of improving fish fitness and resistance against immune challenges. PMID- 26880215 TI - The Potential Use of Fermented Chickpea and Faba Bean Flour as Food Ingredients. AB - Apart from being a rich and inexpensive protein source, legumes provide essential vitamins, minerals and dietary fibre. Considering the nutritional benefits, legumes flour can potentially be incorporated in the development of new products. The aim of this study was to investigate whether fermentation affects the protein content, in vitro protein digestibility, trypsin inhibitor activity and the functionality of proteins in faba bean, desi and kabuli chickpea. Australian grown chickpea and faba bean were selected and initially soaked, de-hulled, dried and milled into flour. This was fermented with lyophilised yoghurt cultures in a 30 degrees C orbital shaker for 16 h. While protein contents in fermented desi and kabuli flour were lower than their raw counterparts (p > 0.05), it was significantly higher in fermented faba bean. A significant increase (9.5%) in in vitro protein digestibility was found in fermented desi. Trypsin inhibitor activity in fermented desi, kabuli and faba bean reduced by 2.7, 1.1 and 4.7%, respectively (p > 0.05). Overall, the in vitro protein digestibility in flour samples increased, while simultaneously reducing the trypsin inhibitor activity. The water absorption capacity of the fermented kabuli flour significantly increased by 11.3%. All fermented flour samples had significantly higher oil absorption capacity than their corresponding raw flour that was likely due to increased insoluble hydrophobic protein. Although, the foaming capacity in all fermented flour samples was significantly lower than their respective raw samples, only fermented desi and faba bean flour showed lower foaming stability (p > 0.05). The present study suggests that fermented legume flour could fulfill the demand for innovative products of higher nutritional value. PMID- 26880216 TI - Protective effects of genetic inhibition of Discoidin Domain Receptor 1 in experimental renal disease. AB - Chronic kidney disease is a progressive incurable pathology affecting millions of people. Intensive investigations aim to identify targets for therapy. We have previously demonstrated that abnormal expression of the Discoidin Domain Receptor 1 (DDR1) is a key factor of renal disease by promoting inflammation and fibrosis. The present study investigates whether blocking the expression of DDR1 after the initiation of renal disease can delay or arrest the progression of this pathology. Severe renal disease was induced by either injecting nephrotoxic serum (NTS) or performing unilateral ureteral obstruction in mice, and the expression of DDR1 was inhibited by administering antisense oligodeoxynucleotides either at 4 or 8 days after NTS (corresponding to early or more established phases of disease, respectively), or at day 2 after ligation. DDR1 antisense administration at day 4 stopped the increase of proteinuria and protected animals against the progression of glomeruloneprhitis, as evidenced by functional, structural and cellular indexes. Antisense administration at day 8 delayed progression -but to a smaller degree- of renal disease. Similar beneficial effects on renal structure and inflammation were observed with the antisense administration of DDR1 after ureteral ligation. Thus, targeting DDR1 can be a promising strategy in the treatment of chronic kidney disease. PMID- 26880217 TI - Photodegradation of diethyl phthalate with PANi/CNT/TiO2 immobilized on glass plate irradiated with visible light and simulated sunlight-effect of synthesized method and pH. AB - Diethyl phthalate (DEP) is one of the most common phthalates for industrial use and has widely spread in environment. A series of PANi/CNT/TiO2 potocatalysts immobilized on glass plate irradiated with visible light were presented to degrade DEP in this study. The PANi/CNT/TiO2 potocatalysts were fabricated by co doping with polyaniline (PANi) and two functionalized CNT (CNT-COCl and CNT-COOH) onto TiO2 followed by a hydrothermal synthesis and a sol-gel hydrolysis. Doping of PANi resulted in the absorption edge of the fabricated potocatalysts shifting to 421-437nm and the most distinguished red-shift effect was found in hydrothermal synthesized photocatalysts. The best DEP degradation of 41.5-59.0% and 44.5-67.4% was found in the simulated sunlight system irradiated for 120min for sol-gel hydrolysis PANi/CNT/TiO2 photocatalysts and hydrothermal synthesized ones, respectively. The optimum pH was determined at 5.0 and 7.0 for the two PANi/CNT/TiO2 photocatalysts mentioned above, respectively. The reusability of the sol-gel hydrolyzed photocatalysts up to 5 times was observed no decline in the photodegradation efficiency but less photocatalytic stability of the hydrothermal synthesized ones was found. Meanwhile, the active species of OH radicals generated in the DEP degradation system was identified by free radical scavenging experiments. PMID- 26880218 TI - Epidermal growth factor induces p38 MAPK-dependent G0/G1-to-S transition in prostate cancer cells upon androgen deprivation conditions. AB - Epidermal growth factor (EGF) is thought to contribute to the emergence of castration-resistant (CR) prostate tumors by inducing proliferation of cancer cells despite the low levels of circulating androgens achieved by androgen deprivation therapy. We show that, in LNCaP cells, androgen deprivation induces arrest in the G0/G1 cell cycle phase, and that EGF partially rescues this arrest without affecting cell death. Inhibition of p38 MAPK, but not MEK or IKK-beta, completely abrogates the EGF-induced proliferation of LNCaP cells in androgen depleted medium, and decreases the fraction of G0/G1-arrested cells. Our results suggest that EGF enables prostate cancer cells to overcome the growth restriction imposed by androgen deprivation by stimulating G0/G1-to-S transition via p38 MAPK. These results suggest the potential of developing therapies for advanced prostate cancer that block the G0/G1 to S transition, such as by targeting p38 MAPK, or that aim to induce apoptosis in G0/G1-arrested cancer cells. PMID- 26880219 TI - A universal mechanism of extreme events and critical phenomena. AB - The occurrence of extreme events and critical phenomena is of importance because they can have inquisitive scientific impact and profound socio-economic consequences. Here we show a universal mechanism describing extreme events along with critical phenomena and derive a general expression of the probability distribution without concerning the physical details of individual events or critical properties. The general probability distribution unifies most important distributions in the field and demonstrates improved performance. The shape and symmetry of the general distribution is determined by the parameters of the fluctuations. Our work sheds judicious insights into the dynamical processes of complex systems with practical significance and provides a general approach of studying extreme and critical episodes in a combined and multidisciplinary scheme. PMID- 26880221 TI - Remarkably enhanced thermal transport based on a flexible horizontally-aligned carbon nanotube array film. AB - It has been more than a decade since the thermal conductivity of vertically aligned carbon nanotube (VACNT) arrays was reported possible to exceed that of the best thermal greases or phase change materials by an order of magnitude. Despite tremendous prospects as a thermal interface material (TIM), results were discouraging for practical applications. The primary reason is the large thermal contact resistance between the CNT tips and the heat sink. Here we report a simultaneous sevenfold increase in in-plane thermal conductivity and a fourfold reduction in the thermal contact resistance at the flexible CNT-SiO2 coated heat sink interface by coupling the CNTs with orderly physical overlapping along the horizontal direction through an engineering approach (shear pressing). The removal of empty space rapidly increases the density of transport channels, and the replacement of the fine CNT tips with their cylindrical surface insures intimate contact at CNT-SiO2 interface. Our results suggest horizontally aligned CNT arrays exhibit remarkably enhanced in-plane thermal conductivity and reduced out-of-plane thermal conductivity and thermal contact resistance. This novel structure makes CNT film promising for applications in chip-level heat dissipation. Besides TIM, it also provides for a solution to anisotropic heat spreader which is significant for eliminating hot spots. PMID- 26880222 TI - Current topics in the multimodality treatment of locally advanced rectal cancer. AB - The multimodality approach to the treatment of locally advanced rectal cancer has evolved to include neoadjuvant radiotherapy with or without concurrent chemotherapy, total mesorectal excision and adjuvant fluoropyrimidine-based chemotherapy. Though this broad strategy has yielded improvements in local control compared with historical data, overall survival remains largely unchanged. Current investigations focus on improving patient selection through new imaging modalities, improving surgical techniques, incorporating more aggressive systemic treatment regimens and the selective use of radiation. Here, we review emerging data regarding newer staging techniques, neoadjuvant chemotherapy, optimal timing of surgery, selective use of radiation and nonoperative approaches to the management of locally advanced rectal cancers. PMID- 26880220 TI - The Total Incidence of Complications and the Impact of an Anticoagulation Regime on Adverse Events After Cryoballoon Ablation of Atrial Fibrillation: A Single Center Study of 409 Patients. AB - AIM: Data evaluating the complications of pulmonary vein isolation (PVI) using second-generation cryoballoons (CB) related to different anticoagulation regimes are limited. This study evaluates the total complications and the impact of novel oral anticoagulants (NOACs) compared to phenprocoumon on adverse events in the setting of PVI using CB. METHODS AND RESULTS: PVI was performed using second generation CB by two experienced investigators. A total of 409 patients (58.9% male; mean age = 61 +/- 10 years) with atrial fibrillation were included in this study. In group I, 150/409 (36.7%) patients received phenprocoumon therapy, and in group II, 259/409 (63.3%) patients were treated with NOACs (rivaroxaban: n = 193; dabigatran: n = 48; and apixaban: n = 18). In both groups, the rates of major complications were similar (group I [phenprocoumon]: four pts (2.7%) vs. Group II [NOACs]: seven pts (2.7%); P = 0.999). In this cohort, 275 patients were ablated with the bonus freeze protocol, and 134 patients were ablated without bonus freezes. The procedure duration significantly decreased with the bonus freeze protocol from 102.3 +/- 24.6 min to 68.5 +/- 16.2 min (P < 0.001). The impact of the bonus freeze on the postprocedural increase of C-reactive protein (CRP) levels was significant compared to the postprocedural CRP levels after procedures without the bonus freeze protocol (postprocedural CRP level+ bonus protocol: 1.6 +/- 1.2 mg/L vs. postprocedural CRP level+ nonbonus protocol: 1.3 +/- 1.3 mg/L; P = 0.04). CONCLUSION: The incidence of adverse events in PVI using the second-generation CB with the periprocedural administration of NAOCs was not significantly different compared to phenprocoumon. Further, large-scale randomized studies are needed to evaluate the safety of two anticoagulation regimes comparing vitamin K antagonists and NOACs, as well as different NOAC regimes, in patients undergoing PVI using cryoballoon ablation. PMID- 26880224 TI - Effects of 3,4-methylenedioxymethamphetamine on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting. AB - The drug 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy", "molly") is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a small (n=12) within-subjects double-blind placebo controlled study of the effects of 1.5 mg/kg oral MDMA on social emotions and autobiographical disclosure in a controlled setting. MDMA displayed both sedative- and stimulant-like effects, including increased self-report anxiety. At the same time, MDMA positively altered evaluation of the self (i.e. increasing feelings of authenticity) while decreasing concerns about negative evaluation by others (i.e. decreasing social anxiety). Consistent with these feelings, MDMA increased how comfortable participants felt describing emotional memories. Overall, MDMA produced a prosocial syndrome that seemed to facilitate emotional disclosure and that appears consistent with the suggestion that it represents a novel pharmacological class. PMID- 26880225 TI - Time course of pharmacokinetic and hormonal effects of inhaled high-dose salvinorin A in humans. AB - Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the Salvia divinorum plant, which has been used for hallucinogenic effects. Previous research on salvinorin A pharmacokinetics likely underestimated plasma levels typically resulting from the doses administered due to inefficient vaporization and not collecting samples during peak drug effects. Six healthy adults inhaled a single high dose of vaporized salvinorin A (n = 4, 21 mcg/kg; n = 2, 18 mcg/kg). Participant- and monitor-rated effects were assessed every 2 min for 60 min post-inhalation. Blood samples were collected at 13 time points up to 90 min post-inhalation. Drug levels peaked at 2 min and then rapidly decreased. Drug levels were significantly, positively correlated with participant and monitor drug effect ratings. Significant elevations in prolactin were observed beginning 5 min post-inhalation and peaking at 15 min post-inhalation. Cortisol showed inconsistent increases across participants. Hormonal responses were not well correlated with drug levels. This is the first study to demonstrate a direct relationship between changes in plasma levels of salvinorin A and drug effects in humans. The results confirm the efficacy of an inhalation technique for salvinorin A. PMID- 26880228 TI - Scalable synthesis of Cu-based ultrathin nanowire networks and their electrocatalytic properties. AB - In this research, we developed an easy way to generate CuM (M = Pd, Pt and PdPt) ultrathin nanowire networks by simply injecting the metallic precursors into an aqueous solution which contained sodium borohydride under vigorous stirring. The reaction can be finished quickly without needing any other reagents, thus leaving the products with a clean surface. The prepared materials show an ultrathin diameter of less than 5 nanometers. The reaction can be easily amplified, resulting in scalable products. These properties combined with the superior catalytic performance of the prepared CuM nanowire networks underpin their potential use in glycerol electrooxidation reaction. PMID- 26880227 TI - Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery. AB - BACKGROUND: Previous studies have shown that recovery of colonic transit is a major determinant of post-operative ileus and clinical recovery after gastrointestinal surgery. Prucalopride is a highly selective 5-hydroxytryptamine receptor-4 agonist with colonic pro-motility effects. AIM: To evaluate the effect and safety of prucalopride on post-operative ileus and surgical outcomes after elective gastrointestinal surgery. METHODS: In this phase II randomised clinical trial, 110 patients undergoing elective gastrointestinal surgery were randomised to either oral prucalopride (2 mg/day) (n = 55) or placebo (n = 55). Intervention was started 24 h after surgery and stopped after defecation or maximally at 7 days. The primary outcome was time to defecation. Secondary outcomes included time to first passage of flatus, tolerance of solid food, nasogastric tube reinsertion, post-operative length of stay, hospital readmission, overall cost, time to walk independently, surgical complications and inflammatory parameters. RESULTS: Patients who received prucalopride had a shorter time to defecation (65.0 vs. 94.5 h, P = 0.001), passage of flatus (53.0 vs. 73.0 h, P < 0.001), and post-operative length of stay (7.0 vs. 8.0 days, P = 0.001) than controls. The number of patients with prolonged ileus (>5 days) (16.4% vs. 34.5%, P = 0.026) and the C-reactive protein level on post-operative day 5 (35.67 vs. 59.07 mg/L, P = 0.040) were lower in the prucalopride group. There was no significant difference in post-operative Clavien-Dindo grade III and IV complications (P = 0.606) between the groups. CONCLUSION: Prucalopride is a safe and effective treatment to reduce post-operative ileus and systemic inflammation without affecting post-operative complications in patients undergoing elective gastrointestinal surgery. ClinicalTrials.gov: NCT02004652. PMID- 26880229 TI - Targeted activation of CREB in reactive astrocytes is neuroprotective in focal acute cortical injury. AB - The clinical challenge in acute injury as in traumatic brain injury (TBI) is to halt the delayed neuronal loss that occurs hours and days after the insult. Here we report that the activation of CREB-dependent transcription in reactive astrocytes prevents secondary injury in cerebral cortex after experimental TBI. The study was performed in a novel bitransgenic mouse in which a constitutively active CREB, VP16-CREB, was targeted to astrocytes with the Tet-Off system. Using histochemistry, qPCR, and gene profiling we found less neuronal death and damage, reduced macrophage infiltration, preserved mitochondria, and rescued expression of genes related to mitochondrial metabolism in bitransgenic mice as compared to wild type littermates. Finally, with meta-analyses using publicly available databases we identified a core set of VP16-CREB candidate target genes that may account for the neuroprotective effect. Enhancing CREB activity in astrocytes thus emerges as a novel avenue in acute brain post-injury therapeutics. PMID- 26880230 TI - Intravoxel incoherent motion diffusion-weighted imaging analysis of diffusion and microperfusion in grading gliomas and comparison with arterial spin labeling for evaluation of tumor perfusion. AB - PURPOSE: To determine the utility of intravoxel incoherent motion (IVIM) imaging in grading gliomas and compare IVIM perfusion metrics with arterial spin labeling (ASL)-derived cerebral blood flow (CBF). MATERIALS AND METHODS: Fifty-two patients with pathologically confirmed gliomas underwent IVIM and ASL imaging at 3.0T. IVIM perfusion-related diffusivity (D*), perfusion fraction (f), product of f and D*(f*D*), true diffusivity (D), and apparent diffusion coefficient (ADC) were obtained to distinguish glioma grades. The CBF derived from pseudocontinuous ASL within the solid tumor was compared and correlated with IVIM perfusion metrics for grading of gliomas. Values were also normalized to the contralateral normal-appearing white matter. Receiver-operating characteristic was performed to determine diagnostic efficiency. The reliability was estimated with intraclass coefficient, coefficient of variance, and Bland-Altman plots. RESULTS: IVIM perfusion metrics and CBF were significantly higher in the high-grade than the low-grade gliomas (P < 0.001), ADC and D were significantly lower in the high grade than the low-grade gliomas (P < 0.001). f*D* differed significantly between grades II through IV (P < 0.05 for all). The other metrics showed significant difference between grade II and grade III (P < 0.05 for all). Area under the curve (AUC) was largest for f*D* in distinguishing high-grade from low-grade gliomas (AUC = 0.979, P < 0.001) and between grade II and grade III (AUC = 0.957, P < 0.001). f*D* improved diagnostic performance of CBF in grading gliomas and showed strong correlation with CBF (r = 0.696, P < 0.001). CONCLUSION: IVIM derived metrics are promising biomarkers in preoperative grading gliomas. IVIM imaging may be an additive method to ASL and ADC for evaluating tumor perfusion and diffusion. J. Magn. Reson. Imaging 2016;44:620-632. PMID- 26880231 TI - Vulvar cancer: initial management and systematic review of literature on currently applied treatment approaches. AB - This review provides guidelines and aims to estimate utilisation rates of treatment modalities applied in vulvar cancer. Current standards of treatment are as follows: wide local excision instead of radical vulvectomy in the case of small tumour (T < 2 cm), no lymph node dissection in the case of a micro-invasive tumour (invasion <1 mm), unilateral lymph node dissection in the case of a lateral tumour and inguinal-femoral lymphadenectomy by separate incisions instead of en bloc inguinal-femoral lymph node excision. Implementation of sentinel lymph node biopsy in patients with tumours not exceeding 4 cm is safe and efficiently eliminates redundant groin dissections. Pre-operative treatment with chemoradiotherapy reduces tumour size and improves surgical excision of inoperable primary tumours or fixed lymph nodes, but side effects are considerable. Literature search performed using PubMed database (from: 1 June 2005 to 1 June 2015) with the terms 'consecutive', 'vulvar cancer', 'treatment' identified seven full-text manuscripts, including data on 1114 patients. Utilisation rates of neoadjuvant radiochemotherapy, chemotherapy alone, surgery, adjuvant radiotherapy and adjuvant radiochemotherapy were 5.9%, 0.3%, 89.3%, 22.6% and 0.2% respectively. An evidence-based estimation of appropriate rates of surgery, radiotherapy and chemotherapy for vulvar cancer is needed to compare management reflecting guidelines with presented here real frequency of applied modalities. PMID- 26880226 TI - Individual differences in timing of peak positive subjective responses to d amphetamine: Relationship to pharmacokinetics and physiology. AB - Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential. PMID- 26880232 TI - Body shape and size in 6-year old children: assessment by three-dimensional photonic scanning. AB - BACKGROUND: Body shape and size are typically described using measures such as body mass index (BMI) and waist circumference, which predict disease risks in adults. However, this approach may underestimate the true variability in childhood body shape and size. OBJECTIVE: To use a comprehensive three dimensional photonic scan approach to describe variation in childhood body shape and size. SUBJECTS/METHODS: At age 6 years, 3350 children from the population based 2004 Pelotas birth cohort study were assessed by three-dimensional photonic scanner, traditional anthropometry and dual X-ray absorptiometry. Principal component analysis (PCA) was performed on height and 24 photonic scan variables (circumferences, lengths/widths, volumes and surface areas). RESULTS: PCA identified four independent components of children's body shape and size, which we termed: Corpulence, Central:peripheral ratio, Height and arm lengths, and Shoulder diameter. Corpulence showed strong correlations with traditional anthropometric and body composition measures (r>0.90 with weight, BMI, waist circumference and fat mass; r>0.70 with height, lean mass and bone mass); in contrast, the other three components showed weak or moderate correlations with those measures (all r<0.45). There was no sex difference in Corpulence, but boys had higher Central:peripheral ratio, Height and arm lengths and Shoulder diameter values than girls. Furthermore, children with low birth weight had lower Corpulence and Height and arm lengths but higher Central:peripheral ratio and Shoulder diameter than other children. Children from high socio-economic position (SEP) families had higher Corpulence and Height and arm lengths than other children. Finally, white children had higher Corpulence and Central:peripheral ratio than mixed or black children. CONCLUSIONS: Comprehensive assessment by three-dimensional photonic scanning identified components of childhood body shape and size not captured by traditional anthropometry or body composition measures. Differences in these novel components by sex, birth weight, SEP and skin colour may indicate their potential relevance to disease risks. PMID- 26880233 TI - The effect of the accessory proteins, soluble CD14 and lipopolysaccharide-binding protein on Toll-like receptor 4 activity in human monocytes and adipocytes. AB - BACKGROUND: There is a growinge body of evidence pointing towards an important role for Toll-like receptors (TLR) especially TLR4 in obesity and metabolic syndrome. OBJECTIVE: Owing to the paucity of data on the effect of the accessory proteins, lipopolysaccharide (LPS)-binding protein (LBP) and soluble CD14 (sCD14) on TLR4 activation, the present study was undertaken to examine the effect of sCD14 and LBP on TLR4 activation in pivotal cells of meta-inflammation, monocytes and adipocytes. METHODS: The dose-response effects of sCD14 and LBP on TLR4 protein abundance in monocytes obtained from normal human volunteers was determined by flow cytometry and in human-differentiated adipocytes by western blotting. Additionally, the nuclear factor-kappaB (NF-kappaB) p65 and downstream biomediators interleukin (IL)-1beta, IL-8, IL-6 and tumor necrosis factor (TNF) alpha were measured in the cell culture supernatants by ELISA (enzyme-linked immunosorbent assay). RESULTS: In LPS-primed monocytes, sCD14 but not LBP, augments both TLR4 abundance and inflammatory biomediators (IL-1beta, IL-8, IL-6 and TNF-alpha).sCD14 also showed a similar effect in LPS-primed human adipocytes by augmenting TLR4 protein expression and activity in terms of NF-kappaB p65 and downstream biomediators (IL-1beta, IL-8, IL-6 and TNF-alpha). LBP at the highest concentration only promoted secretion of IL-8 and TNF-alpha. However in both monocytes and adipocytes, the effect of sCD14 was superior to LBP. CONCLUSIONS: In the present report, we make the novel observation that sCD14 compared with LBP, offers a preferred target to ameliorate TLR especially TLR4-induced inflammation and insulin resistance in human obesity and metabolic syndrome. PMID- 26880235 TI - Subclassification of fatty liver by its pathogenesis: cIEFing is believing. AB - Fatty liver, also termed hepatic steatosis or fatty liver disease, is a condition characterized by excess fat accumulation in the liver. Common causes of fatty liver include obesity, ageing, medications, genetic disorders, viral hepatitis, excess alcohol or toxins. This diversity in pathogenesis is matched by an equally diverse spectrum of consequences, whereby some individuals remain asymptomatic yet others progress through a series of inflammatory, fibrotic and metabolic disorders that can lead to liver failure, cancer or diabetes. Current treatment approaches for fatty liver do not differ by disease aetiology and primarily involve weight loss strategies or management of co-morbidities. In a recent paper published in this journal, Urasaki et al used capillary isoelectric focusing (cIEF) to create profiles of protein post-translational modifications that distinguish four different models of fatty liver in mice. Importantly, this new cIEF approach has the potential to provide rapid individualized diagnosis of fatty liver pathogenesis that may enable more accurate and personalized treatment strategies. Further testing and optimization of cIEF as a diagnostic screening tool in humans is warranted. PMID- 26880234 TI - A cross sectional study of anemia and iron deficiency as risk factors for arsenic induced skin lesions in Bangladeshi women. AB - BACKGROUND: In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. METHODS: We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions. RESULTS: We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L) compared to women with normal hemoglobin levels [Odds Ratio (OR) = 3.32, 95% Confidence Intervals (CI): 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75% of the women with anemia had adequate iron stores (serum ferritin >= 12 MUg/L), suggesting that the majority of anemia detected in this population was unrelated to iron depletion. CONCLUSIONS: Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue. PMID- 26880236 TI - Transfusion Risk and Clinical Knowledge (TRACK) Score and Cardiac Surgery in Patients Refusing Transfusion. AB - OBJECTIVE: The Transfusion Risk and Clinical Knowledge (TRACK) score is a simple tool to predict the chance of undergoing blood transfusion in cardiac surgery. The authors evaluated the relationship between the TRACK score and clinical outcomes of cardiac surgery in patients who refused blood transfusion. DESIGN: An observational study. SETTING: A single hospital. PARTICIPANTS: Seventy-six adult Jehovah's Witnesses refusing blood transfusion who underwent cardiac surgeries. INTERVENTIONS: Patients were divided into 2 groups according to their TRACK score: low-risk group (n = 57, TRACK score of less than 13) and high-risk group (n = 19, TRACK score of 13 or more). Perioperative and long-term clinical outcomes were compared between the 2 groups. MEASUREMENTS AND MAIN RESULTS: The operative mortality was 0% in the low-risk group, and 21.1% (n = 4) in the high risk group (p = 0.003). The incidence of major postoperative complications was higher in the high-risk group (57.9%) than in the low-risk group (17.5%) (p = 0.002). The high-risk group had more postoperative bleeding-related complications (21.1%) than did the low-risk group (1.8%) (p = 0.013). There were no significant differences of predictive performance in mortality and morbidity between the TRACK score and EuroSCORE II. CONCLUSION: In cardiac surgery patients refusing transfusions, the TRACK score predicted postoperative morbidity and mortality of cardiac surgery. PMID- 26880237 TI - Phenyl-Modified Carbon Nitride Quantum Dots with Distinct Photoluminescence Behavior. AB - A novel type of quantum dot (Ph-CN) is manufactured from graphitic carbon nitride by "lining" the carbon nitride structure with phenyl groups through supramolecular preorganization. This approach requires no chemical etching or hydrothermal treatments like other competing nanoparticle syntheses and is easy and safe to use. The Ph-CN nanoparticles exhibit bright, tunable fluorescence, with a high quantum yield of 48.4 % in aqueous colloidal suspensions. Interestingly, the observed Stokes shift of approximately 200 nm is higher than the maximum values reported for carbon nitride based fluorophores. The high quantum yield and the large Stokes shift are related to the structural surface organization of the phenyl groups, which affects the pi-electron delocalization in the conjugated carbon nitride networks and induces colloidal stability. The remarkable performance of the Ph-CN nanoparticles in imaging is demonstrated by a simple incubation study with HeLa cells. PMID- 26880238 TI - National Perspective of Health Outcomes of 8- to 11-Year-Old Children Born Prematurely and Their Full-Term Peers. AB - The specific aim of this study was to evaluate the health sequelae of preterm birth on children 8 to 11years of age as compared to same age children born at term; selected variables include special health care needs, chronic conditions, and caregiver perception of health. DESIGN/METHODS: A secondary data analysis was conducted to evaluate the health outcomes of children 8 to 11years of age who were born prematurely compared to a sample of children born at term. The 2011/2012 National Survey of Children's Health (NSCH) is a nationally representative telephone interview survey of parents/caregivers of children 0 to 17years of age. Preterm birth was determined by parent report of birth more than 3weeks early. RESULTS: Utilizing the Children with Special Health Care Needs (CSHCN) Screener, 35% of children born prematurely, compared to 24% of children born at term were identified as having a special health care need. The 5 most prevalent conditions were the same in both groups of 8 to 11year old children and in the larger total sample of children 2 to 17years of age. However 82% of children born prematurely were described by parents as having excellent or very good health. CONCLUSIONS: Premature birth places children at increased risk for conditions that impede the crucial activities of childhood (education, psychosocial development and play). These conditions may require both medications and increased health care services. IMPLICATIONS FOR PRACTICE: Understanding the relationship between preterm birth and ongoing health risks has the potential to inform the health care providers' ability to provide care that maximizes the potential of children born prematurely. Health care providers need to be cognizant of this risk, utilizing early screening and encouraging intervention and family supports. PMID- 26880239 TI - Online peer-to-peer support in youth mental health: seizing the opportunity. PMID- 26880240 TI - Correction. PMID- 26880241 TI - Safety of combination antiretroviral prophylaxis in high-risk HIV-exposed newborns: a retrospective review of the Canadian experience. AB - INTRODUCTION: The optimal management of infants born to HIV-positive mothers who are untreated or have detectable viral load prior to delivery remains controversial. Despite the increasing use of combination antiretroviral therapy (cART) for post-exposure prophylaxis (PEP) of neonates at high risk of HIV infection, there is little safety and pharmacokinetic data to support this approach. The objective of this study was to evaluate the safety and tolerability of cART for PEP in HIV-exposed neonates. METHODS: Retrospective study on 148 cART and 145 Zidovudine (ZDV) monotherapy-exposed infants identified from four Canadian centres where cART for PEP has routinely been prescribed in high-risk situations. Physician-reported adverse events and clinical outcomes were extracted by chart review. Haematological and growth parameters at birth, one and six months of age were compared between cART and ZDV-exposed infants using multivariate mixed effects modelling. RESULTS: Non-specific signs and symptoms were reported in 10.2% of cART recipients versus none of the ZDV recipients. Treatment was discontinued prematurely in 9.5% of cART recipients versus 2.1% of ZDV recipients (p=0.01). In the multivariate model, cART recipients had lower mean haemoglobin (decrease of 2.07 g/L) over the 6-month period compared with ZDV recipients (p=0.04), but no effect was seen on absolute neutrophil count. cART recipients had lower weight and smaller head circumference at birth and one month of age compared with ZDV-exposed infants; these differences were no longer significant at six months of age. CONCLUSIONS: cART administered at treatment doses for PEP in neonates was generally well tolerated, though a higher incidence of non-specific signs and symptoms and early treatment discontinuation occurred among cART recipients. PMID- 26880243 TI - Predicting motor impairments among children born extremely preterm or very low birthweight. PMID- 26880242 TI - Episodic memories of relationship quality, procedural knowledge of attachment scripts, and the experience of daughters caring for a parent with dementia. AB - A caregiver's attachment history with their parents may affect the thoughts, feelings, and behavior they now have as they care for a parent with dementia. Participants were 77 daughters of a parent with dementia. The nature of participant conscious episodic memories of their parental figures and unconscious procedural knowledge of caregiving processes (secure base script knowledge) were identified as two aspects of the caregiver's relationship history that may impact their involvement in care, relationship conflict, critical attitudes, and strain. Our findings indicated that the nature of episodic memories of the caregiver relationship history with parental figures were significantly associated with stress and criticism of their parent. Greater unconscious procedural knowledge of the secure base script was associated with caregiver report of less conflict and less involvement in the caregiving tasks. Potential clinical implications of this pattern are also discussed. PMID- 26880244 TI - Xeroderma Pigmentosum Group A Promotes Autophagy to Facilitate Cisplatin Resistance in Melanoma Cells through the Activation of PARP1. AB - Xeroderma pigmentosum group A (XPA), a key protein in the nucleotide excision repair pathway, has been shown to promote the resistance of tumor cells to chemotherapeutic drugs by facilitating the DNA repair process. However, the role of XPA in the resistance of melanoma to platinum-based drugs like cisplatin is largely unknown. In this study, we initially found that XPA was expressed at higher levels in cisplatin-resistant melanoma cells than in cisplatin-sensitive ones. Furthermore, the knockdown of XPA not only increased cellular apoptosis but also inhibited cisplatin-induced autophagy, which rendered the melanoma cells more sensitive to cisplatin. Moreover, we discovered that the increased XPA in resistant melanoma cells promoted poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) activation and that the inhibition of PARP1 could attenuate the cisplatin induced autophagy. Finally, we proved that the inhibition of PARP1 and the autophagy process made resistant melanoma cells more susceptible to cisplatin treatment. Our study shows that XPA can promote cell-protective autophagy in a DNA repair-independent manner by enhancing the activation of PARP1 in melanoma cells resistant to cisplatin and that the XPA-PARP1-mediated autophagy process can be targeted to overcome cisplatin resistance in melanoma chemotherapy. PMID- 26880245 TI - [Usefulness of imaging in large vessel vasculitis]. AB - The imaging is essential for the diagnosis of large vessels arteritis, in order to assess the persistent inflammation of arterial lesions, to evaluate the treatment response and search the vascular complications. In patients with giant cell arteritis (GCA), the aortitis could be suspected in 2 situations: in the presence of general constitutional symptoms or systematic screening of aortitis in patient with confirmed GCA. The frequency of aortitis varies according to the imaging method and could be detected in 40 % of patients with computed tomography and MRI, and approximately in 60 % with FDG-PET/CT. The clinical and prognostic value of systematic detection of aortitis during the GCA remains to be determined. In Takayasu arteritis, imaging is performed to diagnose the large vessels vasculitis, to determine the arterial lesions extension to assess the persistent inflammation of arterial lesions. The persistent vascular inflammation should be suspected in the presence of arterial thickness, of arterial enhancement, a parietal edema and increased arterial FDG uptake (>liver). However, the value of these parameters and the threshold remain to be determined. Thus, the value of FDG-PET/CT and MRI and of parameters used to characterize the persistent arterial inflammation should be further studied. PMID- 26880246 TI - A comparison of methods for extracting influenza viral titer characteristics. AB - Viral titer data collected in vitro or in vivo is often analyzed by extracting viral titer characteristics such as peak viral titer, time of viral peak and area under the curve (AUC). Researchers compare these characteristics in the absence and presence of various concentrations of antivirals in an attempt to quantify the effect of antivirals. Often these characteristics are estimated using only measured data points, although fitting of simple mathematical models to estimate these parameters is becoming more prevalent. In this article, our aim is to compare the estimates of different viral titer characteristics using three different approaches. The first approach is the traditional method that uses estimates based on experimentally measured data. The second approach relies on the use of a linear model to fit the viral titer data. The third approach uses an exponential model for the fitting process and the parameters of interest are extracted from there. The mathematical models are tested using in vivo and in vitro influenza infection data. Estimates of viral titer characteristics using either of the two fitting approaches were similar, but differed from estimates using the traditional method. PMID- 26880247 TI - Association mapping for drought tolerance in barley at the reproductive stage. AB - Drought is an important abiotic stress causing the major crop losses worldwide. Identification of genomic regions associated with drought-related traits is essential for improving drought tolerance in barley. Association mapping was implemented to investigate the associations between 76 SSR markers and six drought-related traits on a set of 107 barley accessions evaluated under well watered and drought-stressed conditions. Highly significant differences between well-watered and drought-stressed conditions were observed in all measured traits. A high level of polymorphism with SSR markers was observed. A total of 36 significant marker-trait associations for drought-related traits were detected. A high extent of significant LD (>61%) was observed between markers on different chromosomes, suggesting epistatic interaction. Several molecular markers are significantly associated with more than one phenotypic trait, suggesting the possible presence of pleiotropic or indirect effects. The phenotypic variation, explained by individual marker-trait associations, ranged from 6.33% to 35.78%. PMID- 26880248 TI - Alpha-synuclein gene variants may predict neurostimulation outcome. PMID- 26880249 TI - IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity. AB - IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of "universal" influenza vaccine. PMID- 26880251 TI - Show Me My Health Plans: a study protocol of a randomized trial testing a decision support tool for the federal health insurance marketplace in Missouri. AB - BACKGROUND: The implementation of the ACA has improved access to quality health insurance, a necessary first step to improving health outcomes. However, access must be supplemented by education to help individuals make informed choices for plans that meet their individual financial and health needs. METHODS/DESIGN: Drawing on a model of information processing and on prior research, we developed a health insurance decision support tool called Show Me My Health Plans. Developed with extensive stakeholder input, the current tool (1) simplifies information through plain language and graphics in an educational component; (2) assesses and reviews knowledge interactively to ensure comprehension of key material; (3) incorporates individual and/or family health status to personalize out-of-pocket cost estimates; (4) assesses preferences for plan features; and (5) helps individuals weigh information appropriate to their interests and needs through a summary page with "good fit" plans generated from a tailored algorithm. The current study will evaluate whether the online decision support tool improves health insurance decisions compared to a usual care condition (the healthcare.gov marketplace website). The trial will include 362 individuals (181 in each group) from rural, suburban, and urban settings within a 90 mile radius around St. Louis. Eligibility criteria includes English-speaking individuals 18-64 years old who are eligible for the ACA marketplace plans. They will be computer randomized to view the intervention or usual care condition. DISCUSSION: Presenting individuals with options that they can understand tailored to their needs and preferences could help improve decision quality. By helping individuals narrow down the complexity of health insurance plan options, decision support tools such as this one could prepare individuals to better navigate enrollment in a plan that meets their individual needs. The randomized trial was registered in clinicaltrials.gov (NCT02522624) on August 6, 2015. PMID- 26880252 TI - Effects of Acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy on Symptom Management and Quality of Life for Cancer Patients: A Meta-Analysis. AB - CONTEXT: Most cancer patients suffer from both the disease itself and symptoms induced by conventional treatment. Available literature on the clinical effects on cancer patients of acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Music Therapy (TCM-FEMT) reports controversial results. OBJECTIVES: The primary objective of this meta-analysis was to evaluate the effect of acupuncture, Tuina, Tai Chi, Qigong, and TCM-FEMT on various symptoms and quality of life (QOL) in patients with cancer; risk of bias for the selected trials also was assessed. METHODS: Studies were identified by searching electronic databases (MEDLINE via both PubMed and Ovid, Cochrane Central, China National Knowledge Infrastructure, Chinese Scientific Journal Database, China Biology Medicine, and Wanfang Database). All randomized controlled trials (RCTs) using acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT published before October 2, 2014, were selected, regardless of whether the article was published in Chinese or English. RESULTS: We identified 67 RCTs (5465 patients) that met our inclusion criteria to perform this meta-analysis. Analysis results showed that a significant combined effect was observed for QOL change in patients with terminal cancer in favor of acupuncture and Tuina (Cohen's d: 0.21-4.55, P < 0.05), whereas Tai Chi and Qigong had no effect on QOL of breast cancer survivors (P > 0.05). The meta-analysis also demonstrated that acupuncture produced small-to large effects on adverse symptoms including pain, fatigue, sleep disturbance, and some gastrointestinal discomfort; however, no significant effect was found on the frequency of hot flashes (Cohen's d = -0.02; 95% CI = -1.49 to 1.45; P = 0.97; I(2) = 36%) and mood distress (P > 0.05). Tuina relieved gastrointestinal discomfort. TCM-FEMT lowered depression level. Tai Chi improved vital capacity of breast cancer patients. High risk of bias was present in 74.63% of the selected RCTs. Major sources of risk of bias were lack of blinding, allocation concealment, and incomplete outcome data. CONCLUSION: Taken together, although there are some clear limitations regarding the body of research reviewed in this study, a tentative conclusion can be reached that acupuncture, Tuina, Tai Chi, Qigong, or TCM-FEMT represent beneficial adjunctive therapies. Future study reporting in this field should be improved regarding both method and content of interventions and research methods. PMID- 26880253 TI - A Mixed-Methods, Randomized, Controlled Feasibility Trial to Inform the Design of a Phase III Trial to Test the Effect of the Handheld Fan on Physical Activity and Carer Anxiety in Patients With Refractory Breathlessness. AB - CONTEXT: The handheld fan is an inexpensive and safe way to provide facial airflow, which may reduce the sensation of chronic refractory breathlessness, a frequently encountered symptom. OBJECTIVES: To test the feasibility of developing an adequately powered, multicenter, multinational randomized controlled trial comparing the efficacy of a handheld fan and exercise advice with advice alone in increasing activity in people with chronic refractory breathlessness from a variety of medical conditions, measuring recruitment rates; data quality; and potential primary outcome measures. METHODS: This was a Phase II, multisite, international, parallel, nonblinded, mixed-methods randomized controlled trial. Participants were centrally randomized to fan or control. All received breathlessness self-management/exercise advice and were followed up weekly for four weeks. Participants/carers were invited to participate in a semistructured interview at the study's conclusion. RESULTS: Ninety-seven people were screened, 49 randomized (mean age 68 years; 49% men), and 43 completed the study. Site recruitment varied from 0.25 to 3.3/month and screening:randomization from 1.1:1 to 8.5:1. There were few missing data except for the Chronic Obstructive Pulmonary Disease Self-Efficacy Scale (two-thirds of data missing). No harms were observed. Three interview themes included 1) a fan is a helpful self-management strategy, 2) a fan aids recovery, and 3) a symptom control trial was welcome. CONCLUSION: A definitive, multisite trial to study the use of the handheld fan as part of self-management of chronic refractory breathlessness is feasible. Participants found the fan useful. However, the value of information for changing practice or policy is unlikely to justify the expense of such a trial, given perceived benefits, the minimal costs, and an absence of harms demonstrated in this study. PMID- 26880255 TI - Improvement of hyperpigmentation within a plexiform neurofibroma after treatment with Q-switched neodymium:yttrium-aluminium-garnet laser. PMID- 26880254 TI - Heart failure and orthostatic hypotension. AB - Orthostatic hypotension (OH) is traditionally defined as a fall of >=20 mmHg in systolic and/or >=10 mmHg in diastolic blood pressure within 3 min of active standing. OH is a common comorbidity among patients with heart failure (HF). A comprehensive review regarding the relationship between OH and HF has not been published in the English literature. Here we provide current information about concomitant HF and OH, including: pathophysiology, methods of evaluation, prevalence, risk factors, prognosis and management of OH in HF patients, as well as the incidence of HF among patients with OH. The prevalence of OH in HF ranges from 8 % among community-living individuals to 83 % in elderly hospitalized patients. Dizziness and palpitations are the most frequent OH symptoms. Main predisposing factors for OH are HF severity, non-ischemic HF etiology, prolonged bed rest, hypertension and polypharmacy. OH in HF is generally managed according to recommendations for treatment of OH in the non-HF population. However, since acceptable pharmacotherapy with fludrocortisone and midodrine is problematic in HF due to adverse effects, the management of OH is based mainly on non pharmacologic interventions. Several prospective epidemiological studies reported that OH is independently associated with an increased risk of developing HF. Since OH is a common and frequently symptomatic condition in HF patients, its clinical implications should be emphasized. Longitudinal studies should be conducted to investigate the prognostic significance and optimal management of OH in the HF population. PMID- 26880256 TI - Granulocyte and granulocyte-macrophage colony stimulating factors for newly diagnosed patients with myelodysplastic syndromes. AB - BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of haematological diseases which are characterised by a uni- or multilineage dysplasia of haematological stem cells. Standard treatment is supportive care of the arising symptoms including red blood cell transfusions or the administration of erythropoiesis-stimulating agents (ESAs) in the case of anaemia or the treatment with granulocyte (G-CSF) and granulocyte-macrophage colony stimulating factors (GM-CSF) in cases of neutropenia. OBJECTIVES: The objective of this review is to assess the evidence for the treatment of patients with MDS with G CSF and GM-CSF in addition to standard therapy in comparison to the same standard therapy or the same standard therapy and placebo. SEARCH METHODS: We searched MEDLINE (from 1950 to 3 December 2015) and CENTRAL (Cochrane Central Register of Controlled Trials until 3 December 2015), as well as conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association, European Society of Medical Oncology) for randomised controlled trials (RCTs). Two review authors independently screened search results. SELECTION CRITERIA: We included RCTs examining G-CSF or GM-CSF in addition to standard therapy in patients with newly diagnosed MDS. DATA COLLECTION AND ANALYSIS: We used hazard ratios (HR) as effect measure for overall survival (OS), progression-free survival (PFS) and time to progression, and risk ratios for response rates, adverse events, antibiotic use and hospitalisation. Two independent review authors extracted data and assessed risk of bias. Investigators of two trials were contacted for subgroup information, however, no further data were provided. G-CSF and GM-CSF were analysed separately. MAIN RESULTS: We screened a total of 566 records. Seven RCTs involving 486 patients were identified, but we could only meta-analyse the two evaluating GM-CSF. We judged the potential risk of bias of these trials as unclear, mostly due to missing information. All trials were randomised and open-label studies. However, three trials were published as abstracts only, therefore we were not able to assess the potential risk of bias for these trials in detail. Overall, data were not reported in a comparable way and patient-related outcomes like survival, time to progression to acute myeloid leukaemia (AML) or the incidence of infections was reported in two trials only.Five RCTs (N = 337) assessed the efficacy of G CSF in combination with standard therapy (supportive care, chemotherapy or erythropoietin). We were not able to perform meta-analyses for any of the pre planned outcomes due to inconsistent and insufficient reporting of data. There is no evidence for a difference for overall survival (hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.44 to 1.47), progression-free survival (only P value provided), progression to AML, incidence of infections and number of red blood transfusions (average number of 12 red blood cell transfusions in each arm). We judged the quality of evidence for all these outcomes as very low, due to very high imprecision and potential publication bias, as three trials were published as abstracts only. Data about quality of life and serious adverse events were not reported in any of the included trials.Two RCTs (N = 149) evaluated GM-CSF in addition to standard therapy (chemotherapy). For mortality (two RCTs; HR 0.88, 95% CI 0.62 to 1.26), we found no evidence for a difference (low-quality evidence). Data for progression-free survival and serious adverse events were not comparable across both studies, without evidence for a difference between both arms (low-quality evidence). For infections, red blood cell and platelet transfusions, we found no evidence for a difference, however, these outcomes were reported by one trial only (low-quality evidence). Time to progression to AML and quality of life were not reported at all.Moreover, we identified two cross-over trials, including 244 patients and evaluating GM-CSF versus placebo, without publishing results for each arm before crossing over. In addition, we identified two ongoing studies, one of which was discontinued due to withdrawal of pharmaceutical support, the other was terminated early, both without publishing results. AUTHORS' CONCLUSIONS: Although we identified seven trials with a total number of 486 patients, and two unpublished, prematurely finished studies, this systematic review mainly shows that there is a substantial lack of data, which might inform the use of G-CSF and GM-CSF for the prevention of infections, prolonging of survival and improvement of quality of life. The impact on progression to AML remains unclear. PMID- 26880257 TI - Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences. AB - Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Matern correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Matern model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Matern model. PMID- 26880258 TI - The Use of Avoidance, Adjustment, Interaction and Acceptance Strategies to Handle Participation Restrictions Among Swedish Men with Early Rheumatoid Arthritis. AB - OBJECTIVES: Living with a chronic disease means learning to live under new circumstances and involves a continuous adaptation to new ways of living. There is increasing knowledge about how people cope with stressful life events and adapt to new life situations. Approximately a third of patients diagnosed with rheumatoid arthritis (RA) are men; however, few studies have described the needs and experiences of men living with RA. The aim of the present study was to explore men's strategies for handling challenges related to participation in everyday life. METHODS: The present study was associated with the prospective Swedish multicentre early arthritis project (given the Swedish acronym TIRA), which, in 2006-2009, included patients with early RA, contemporarily treated, with a mean disease duration of three years. From this cohort, 25 men, aged 20-63 years, were recruited consecutively. Data were collected in individual interviews, using the critical incident technique. The strategies for dealing with the challenges of RA in everyday life were analysed and categorized using content analysis. RESULTS: Men with RA described four types of strategy for dealing with participation restrictions in everyday life: (i) Adjustment strategies - adjust behaviour, movements, medication, equipment and clothing to find new ways to conduct tasks or activities; (ii) Avoidance strategies - avoid activities, movements, social contacts and sometimes medication; (iii) Interaction strategies - say no, ask for help and work together to handle participation restrictions; and (iv) Acceptance strategies - learn to accept RA, with the pain, the slower work pace and the extended time needed. CONCLUSIONS: According to men's lived experiences, a combination of strategies was used to deal with RA, depending on the situation and the experienced restriction. The results provided an understanding of how men with RA manage their disease, to reduce physical, social and emotional challenges. This knowledge may be used further to develop multi-professional interventions and patient education tailored to men with RA. PMID- 26880259 TI - Multimodality Imaging of Cardiac Transthyretin Amyloidosis 16 Years After a Domino Liver Transplantation. AB - We report the case of a 62-year-old man hospitalized in May 2015 for symptomatic heart failure. His medical history included two liver transplantations. The first liver transplantation was performed in 1999 for a mixed alcoholic and hepatitis C related cirrhosis and the patient received the liver of another patient with Val30Met transthyretin amyloidosis using the domino technique. In 2008, he complained of neuropathic pains and an iatrogenic-acquired transthyretin amyloidosis was diagnosed. On cardiac evaluation, amyloidosis was suspected. In March 2010, a second liver transplantation was performed with a deceased donor without complication. In May 2015, a first episode of symptomatic heart failure occurred and cardiac amyloidosis was investigated by a multimodality evaluation. Electrocardiogram, cardiac biomarkers, echocardiography, and cardiac MRI were in favor of the diagnosis of amyloidosis, whereas 99m Tc-dicarboxypropane diphosphonate scintigraphy was not. Endomyocardial biopsy finally confirmed the positive diagnosis of iatrogenic-acquired cardiac amyloidosis. This case is, to the best of our knowledge, the first to report biopsy-proven cardiac amyloidosis induced by domino liver transplantation and progressing heart failure in spite of retransplantation. The diagnostic modalities are discussed. This case should alert physicians to the cardiac risk in domino liver transplanted patients. PMID- 26880260 TI - Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway. AB - The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-beta1 (TGF- beta1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- beta1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF beta1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- beta1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-beta1/Smad2/3 pathway. PMID- 26880262 TI - Catalytic Asymmetric Tandem Reaction of Tertiary Enamides: Expeditious Synthesis of Pyrrolo[2,1-a]isoquinoline Alkaloid Derivatives. AB - Reported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one structure from unique tertiary enamide synthons. A Cu(OTf)2 /chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron-rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1 a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids. PMID- 26880261 TI - The relationship between non-symbolic multiplication and division in childhood. AB - Children without formal education in addition and subtraction are able to perform multi-step operations over an approximate number of objects. Further, their performance improves when solving approximate (but not exact) addition and subtraction problems that allow for inversion as a shortcut (e.g., a + b - b = a). The current study examines children's ability to perform multi-step operations, and the potential for an inversion benefit, for the operations of approximate, non-symbolic multiplication and division. Children were trained to compute a multiplication and division scaling factor (*2 or /2, *4 or /4), and were then tested on problems that combined two of these factors in a way that either allowed for an inversion shortcut (e.g., 8*4/4) or did not (e.g., 8*4/2). Children's performance was significantly better than chance for all scaling factors during training, and they successfully computed the outcomes of the multi step testing problems. They did not exhibit a performance benefit for problems with the a*b/b structure, suggesting that they did not draw upon inversion reasoning as a logical shortcut to help them solve the multi-step test problems. PMID- 26880264 TI - Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity. AB - The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Tissue levels of eCBs were measured by LC-MS while expressions of genes coding for CB1 and CB2 receptors were investigated by qPCR. High-fat diet induced an increase in anandamide (AEA) levels in soleus and EDL (p < 0.02). In soleus of the HFD group, these changes were accompanied by elevated Cnr1 messenger RNA (mRNA) levels (p < 0.05). In EDL, exercise training allowed to reduce significantly this diet induced AEA increase (p < 0.005). 2-Arachidonoylglycerol (2-AG) levels were decreased and increased by high-fat diet in SAT and EDL, respectively (p < 0.04), but not affected by exercise training. Unlike the HFD + training group, 2-AG levels in soleus were also decreased in the HFD group compared to Ctl (p < 0.04). The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations. PMID- 26880265 TI - Requirement of interleukin 7 signaling for anti-tumor immune response under lymphopenic conditions in a murine lung carcinoma model. AB - Induction of lymphopenia before adoptive transfer of T cells was followed by lymphopenia-induced proliferation (LIP) and generated a potent anti-tumor immune response in rodents and in a clinical setting. Previously, we reported that CD28 signaling is essential for the differentiation of functional effector cytotoxic T lymphocytes (CTLs) under lymphopenic conditions and sequential LIP of T cells. In this study, to clarify the correlation between LIP and the anti-tumor effect, LIP was inhibited with interleukin 7 (IL7) receptor blockade at various stages, and the anti-tumor effect then assessed. We confirmed that IL7 signaling at the start of LIP is crucial for the anti-tumor immune response. In contrast, continuous IL7 signaling was not required for tumor regression, although LIP of naive CD8+ T cells is usually regulated by IL7. The expansion and migration of CTLs in lymphopenic hosts depend on IL7 signaling during the induction phase. Here, we propose that IL7 signaling and subsequent LIP of T cells have distinct roles in the induction of T cell immunity during lymphopenia. PMID- 26880266 TI - A Potent HER3 Monoclonal Antibody That Blocks Both Ligand-Dependent and Independent Activities: Differential Impacts of PTEN Status on Tumor Response. AB - HER3/ERBB3 is a kinase-deficient member of the EGFR family receptor tyrosine kinases (RTK) that is broadly expressed and activated in human cancers. HER3 is a compelling cancer target due to its important role in activation of the oncogenic PI3K/AKT pathway. It has also been demonstrated to confer tumor resistance to a variety of cancer therapies, especially targeted drugs against EGFR and HER2. HER3 can be activated by its ligand (heregulin/HRG), which induces HER3 heterodimerization with EGFR, HER2, or other RTKs. Alternatively, HER3 can be activated in a ligand-independent manner through heterodimerization with HER2 in HER2-amplified cells. We developed a fully human mAb against HER3 (KTN3379) that efficiently suppressed HER3 activity in both ligand-dependent and independent settings. Correspondingly, KTN3379 inhibited tumor growth in divergent tumor models driven by either ligand-dependent or independent mechanisms in vitro and in vivo Most intriguingly, while investigating the mechanistic underpinnings of tumor response to KTN3379, we discovered an interesting dichotomy in that PTEN loss, a frequently occurring oncogenic lesion in a broad range of cancer types, substantially blunted the tumor response in HER2-amplified cancer, but not in the ligand-driven cancer. To our knowledge, this represents the first study ascertaining the impact of PTEN loss on the antitumor efficacy of a HER3 mAb. KTN3379 is currently undergoing a phase Ib clinical trial in patients with advanced solid tumors. Our current study may help us optimize patient selection schemes for KTN3379 to maximize its clinical benefits. Mol Cancer Ther; 15(4); 689-701. (c)2016 AACR. PMID- 26880267 TI - Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy. AB - Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge. Here, we used flexible and pH-sensitive polymersomes for payload delivery to peritoneal gastric (MKN-45P) and colon (CT26) carcinoma in mice. Polymersomes were loaded with paclitaxel and in vitro drug release was studied as a function of pH and time. Paclitaxel-loaded polymersomes remained stable in aqueous solution at neutral pH for up to 4 months. In cell viability assay on cultured cancer cell lines (MKN 45P, SKOV3, CT26), paclitaxel-loaded polymersomes were more toxic than free drug or albumin-bound paclitaxel (Abraxane). Intraperitoneally administered fluorescent polymersomes accumulated in malignant lesions, and immunofluorescence revealed an intense signal inside tumors with no detectable signal in control organs. A dual targeting of tumors was observed: direct (circulation-independent) penetration, and systemic, blood vessel-associated accumulation. Finally, we evaluated preclinical antitumor efficacy of paclitaxel-polymersomes in the treatment of MKN-45P disseminated gastric carcinoma using a total dose of 7 mg/kg. Experimental therapy with paclitaxel-polymersomes improved the therapeutic index of drug over free paclitaxel and Abraxane, as evaluated by intraperitoneal tumor burden and number of metastatic nodules. Our findings underline the potential utility of the polymersome platform for delivery of drugs and imaging agents to peritoneal carcinomatosis lesions. Mol Cancer Ther; 15(4); 670-9. (c)2016 AACR. PMID- 26880268 TI - CD20-Targeting Immunotherapy Promotes Cellular Senescence in B-Cell Lymphoma. AB - The CD20-targeting monoclonal antibody rituximab is an established component of immunochemotherapeutic regimens against B-cell lymphomas, where its coadministration with conventional anticancer agents has significantly improved long-term outcome. However, the cellular mechanisms by which rituximab exerts its antilymphoma activity are only partially understood. We show here that rituximab induces typical features of cellular senescence, a long-term growth arrest of viable cells with distinct biologic properties, in established B-cell lymphoma cell lines as well as primary transformed B cells. In addition, rituximab-based immunotherapy sensitized lymphoma cells to senescence induction by the chemotherapeutic compound adriamycin (a.k.a. doxorubicin), and, to a lesser extent, by the antimicrotubule agent vincristine. Anti-CD20 treatment further enhanced secretion of senescence-associated cytokines, and augmented the DNA damage response signaling cascade triggered by adriamycin. As the underlying prosenescence mechanism, we found intracellular reactive oxygen species (ROS) levels to be elevated in response to rituximab, and, in turn, the ROS scavenger N acetylcysteine to largely abrogate rituximab-mediated senescence. Our results, further supported by gene set enrichment analyses in a clinical data set of chronic lymphocytic leukemia patient samples exposed to a rituximab-containing treatment regimen, provide important mechanistic insights into the biologic complexity of anti-CD20-evoked tumor responses, and unveil cellular senescence as a hitherto unrecognized effector principle of the antibody component in lymphoma immunochemotherapy. Mol Cancer Ther; 15(5); 1074-81. (c)2016 AACR. PMID- 26880270 TI - From Umpolung to Alternation: Modified Reactivity of Donor-Acceptor Cyclopropanes Towards Nucleophiles in Reaction with Nitroalkanes. AB - A conceptually new type of donor-acceptor cyclopropane reactivity towards nucleophiles has been disclosed. An essential characteristic of the process is an unusual nucleophilic attack on the C(3)-position of a cyclopropane, combined with typical small ring-opening by cleavage of the C(1)-C(2) bond between the acceptor and the donor. Based on this new reaction between cyclopropane-1,1-diesters and nitroalkanes, we developed a convenient approach to gamma-nitroesters that can be efficiently transformed to the substituted pyrrolidones, structural analogues of racetame family drugs (rolipram, phenylpiracetam, etc.). PMID- 26880269 TI - Chondroitin sulfate prevents peritoneal fibrosis in mice by suppressing NF-kappaB activation. AB - Long-term peritoneal dialysis causes peritoneal fibrosis, and previous reports suggest that inflammation plays a critical role in peritoneal fibrosis. Chondroitin sulfate (CS) suppresses the inflammatory response by preventing activation of nuclear factor (NF)-kappaB. We examined the effect of CS on the peritoneal fibrosis induced by chlorhexidine gluconate (CG) in mice. CS or water was administered daily. We divided mice into four groups: administered vehicle and water (control); administered vehicle and CS (CS); administered CG and water (CG); and administered CG and CS (CG+CS). Morphologic changes were assessed by Masson's trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry. Activation of NF-kappaB was examined by southwestern histochemistry. CS administration suppressed the progression of submesothelial thickening. The numbers of inflammation- and fibrosis-associated factors -positive cells were significantly decreased in the CG+CS group, compared to the CG group. Based on SWH, the CG+CS group contained significantly fewer NF kappaB-activated cells than the CG group. Our results indicate that CS suppresses peritoneal fibrosis via suppression of NF-kappaB activation. These results suggest that CS has therapeutic potential for peritoneal fibrosis. PMID- 26880272 TI - The Use of Ultrasound to Improve Axillary Vein Access and Minimize Complications during Pacemaker Implantation. AB - BACKGROUND: The Agency for Healthcare Research and Quality in the United States recommends the use of ultrasound (US) for central venous access to improve patient outcomes. However, in a recent publication, US is still underutilized for axillary vein access during pacemaker implantation. OBJECTIVE: We sought to describe a technique for US-guided axillary vein access during pacemaker implantation and to report complication rates and success rate. METHODS: Retrospective data collection included success rate and complications on all pacemaker implants by one operator since implementing the systematic use of US at our institution, from November 2012 to January 2015. For the last 59 cases, data were collected prospectively to include time of venous access and number of attempts. RESULTS: A total of 403 consecutive patients were included in the analysis. Two leads were implanted in 255 cases and one lead was implanted in 148 cases. The rate of successful US-guided access was 99.25%. There were no access related complications. The average number of venipuncture attempts was 1.18 per patient. The average time to obtain venous access was 2.24 minutes including the time to apply the sterile US sleeve. CONCLUSION: The described technique has the potential to improve the success rate of axillary vein access and minimize complications during pacemaker implantation. PMID- 26880273 TI - Transcriptomic response to injury sheds light on the physiological costs of reproduction in ant queens. AB - The trade-off between reproduction and longevity is widespread among multicellular organisms. As an important exception, the reproductive females of perennial social insects (ants, honeybees, termites) are simultaneously highly fertile and very long-lived relative to their nonreproductive nestmates. The observation that increased fecundity is not coupled with decreased lifespan suggests that social insect queens do not have to reallocate resources between reproduction and self-maintenance. If queens have to compensate for the costs of reproduction on the level of the individual, the activation of other energy demanding physiological processes might force them to reduce the production of eggs. To test this hypothesis in ant queens, we increased immunity costs by injury and measured the effect of this treatment on egg-laying rates and genomewide gene expression. Amputation of both middle legs led to a temporary decrease in egg-laying rates and affected the expression of 947 genes corresponding to 9% of the transcriptome. The changes comprised the upregulation of the immune and wound healing response on the one hand, and the downregulation of germ cell development, central nervous system development and learning ability on the other hand. Injury strongly influenced metabolism by inducing catabolism and repressing amino acid and nitrogen compound metabolism. By comparing our results to similar transcriptomic studies in insects, we found a highly consistent upregulation of immune genes due to sterile and septic wounding. The gene expression changes, complemented by the temporary decline of egg-laying rates, clearly reveal a trade-off between reproduction and the immune response in social insect queens. PMID- 26880271 TI - Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway. AB - Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A-C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 MUM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 MUM). PMID- 26880275 TI - Down-to-up transanal rectal resection with total mesorectal excision assisted by single-incision laparoscopy - a video vignette. PMID- 26880274 TI - Dynamic changes in protein interaction between AKAP95 and Cx43 during cell cycle progression of A549 cells. AB - Here we show that A-kinase anchoring protein 95 (AKAP95) and connexin 43 (Cx43) dynamically interact during cell cycle progression of lung cancer A549 cells. Interaction between AKAP95 and Cx43 at different cell cycle phases was examined by tandem mass spectrometry(MS/MS), confocal immunofluorescence microscopy, Western blot, and co-immunoprecipitation(Co-IP). Over the course of a complete cell cycle, interaction between AKAP95 and Cx43 occurred in two stages: binding stage from late G1 to metaphase, and separating stage from anaphase to late G1. The binding stage was further subdivided into complex binding to DNA in interphase and complex separating from DNA in metaphase. In late G1, Cx43 translocated to the nucleus via AKAP95; in anaphase, Cx43 separated from AKAP95 and aggregated between two daughter nuclei. In telophase, Cx43 aggregated at the membrane of the cleavage furrow. After mitosis, Cx43 was absent from the furrow membrane and was located in the cytoplasm. Binding between AKAP95 and Cx43 was reduced by N-(2-[P-Bromocinnamylamino]-ethyl)-5-isoquinolinesulfonmide (H89) treatment and enhanced by Forskolin. dynamic interaction between AKAP95 and Cx43 varies with cell cycle progression to regulate multiple biological processes. PMID- 26880276 TI - Nanoarchitectured Nb2O5 hollow, Nb2O5@carbon and NbO2@carbon Core-Shell Microspheres for Ultrahigh-Rate Intercalation Pseudocapacitors. AB - Li-ion intercalation materials with extremely high rate capability will blur the distinction between batteries and supercapacitors. We construct a series of nanoarchitectured intercalation materials including orthorhombic (o-) Nb2O5 hollow microspheres, o-Nb2O5@carbon core-shell microspheres and tetragonal (t-) NbO2@carbon core-shell microspheres, through a one-pot hydrothermal method with different post-treatments. These nanoarchitectured materials consist of small nanocrystals with highly exposed active surface, and all of them demonstrate good Li(+) intercalation pseudocapacitive properties. In particular, o-Nb2O5 hollow microspheres can deliver the specific capacitance of 488.3 F g(-1), and good rate performance of 126.7 F g(-1) at 50 A g(-1). The o-Nb2O5@carbon core-shell microspheres show enhanced specific capacitance of 502.2 F g(-1) and much improved rate performance (213.4 F g(-1) at 50 A g(-1)). Furthermore, we demonstrate for the first time, t-NbO2 exhibits much higher rate capability than o-Nb2O5. For discharging time as fast as 5.9 s (50 A g(-1)), it still exhibits a very high specific capacitance of 245.8 F g(-1), which is 65.2% retention of the initial capacitance (377.0 F g(-1) at 1 A g(-1)). The unprecedented rate capability is an intrinsic feature of t-NbO2, which may be due to the conductive lithiated compounds. PMID- 26880278 TI - Achieving near-infrared emission in platinum(II) complexes by using an extended donor-acceptor-type ligand. AB - A series of C^N ligands with donor-acceptor (D-A) frameworks, i.e. TPA-BTPy, TPA BTPy-Fl and Fl(TPA-BTPy)2, as well as their mono- and di-nuclear platinum(II) complexes of (TPA-BTPy)Pt(pic), (TPA-BTPy-Fl)Pt(pic) and [Fl(TPA-BTPy)2]Pt2(pic)2 are respectively designed and synthesized, in which triphenylamine (TPA) and fluorene (Fl) are used as the D units, 4-(pyrid-2-yl)benzothiadiazole (BTPy) as the A unit, and the picolinate anion (pic) as the auxiliary ligand. Their thermal, photophysical and electrochemical characteristics were investigated. Compared to mono-nuclear platinum complexes and their free ligands, this dinuclear one of [Fl(TPA-BTPy)2]Pt2(pic)2 shows an obvious interaction from the platinum atom to ligand and dual emission peaks at 828 and 601 nm in thin films. Upon oxidation with antimony pentachloride in dichloromethane, charge transfer transitions between the platinum and ligand are observed for the three complexes. The single-emissive-layer polymer light-emitting devices doped with [Fl(TPA BTPy)2]Pt2(pic)2 display a strong electroluminescence with dual emission peaks at 780 and 600 nm at a dopant concentration over 4 wt%. A maximum external quantum efficiency of 0.02% with a radiance of 59 MUW cm(-2) is obtained in the device at 30 wt% dopant concentration. This work indicates that the use of an extended D-A type ligand is an effective strategy to achieve NIR emission for platinum complexes in PLEDs. PMID- 26880277 TI - Surface-Nanoengineered Bacteria for Efficient Local Enrichment and Biodegradation of Aqueous Organic Wastes: Using Phenol as a Model Compound. AB - Bacteria armed with thermally responsive silica nanoparticles are prepared for efficient biodegradation of phenol in water. The adsorption and release properties of thermally responsive silica nanoparticles under different temperatures can lead to a higher local concentration of phenol, which accelerates the biodegradation process. PMID- 26880279 TI - Local adaptation to osmotic environment in killifish, Fundulus heteroclitus, is supported by divergence in swimming performance but not by differences in excess post-exercise oxygen consumption or aerobic scope. AB - Regulation of internal ion homeostasis is essential for fishes inhabiting environments where salinities differ from their internal concentrations. It is hypothesized that selection will reduce energetic costs of osmoregulation in a population's native osmotic habitat, producing patterns of local adaptation. Killifish, Fundulus heteroclitus, occupy estuarine habitats where salinities range from fresh to seawater. Populations inhabiting an environmental salinity gradient differ in physiological traits associated with acclimation to acute salinity stress, consistent with local adaptation. Similarly, metabolic rates differ in populations adapted to different temperatures, but have not been studied in regard to salinity. We investigated evidence for local adaptation between populations of killifish native to fresh and brackish water habitats. Aerobic scope (the difference between minimum and maximum metabolic rates), excess post-exercise oxygen consumption, and swimming performance (time and distance to reach exhaustion) were used as proxies for fitness in fresh and brackish water treatments. Swimming performance results supported local adaptation; fish native to brackish water habitats performed significantly better than freshwater-native fish at high salinity while low salinity performance was similar between populations. However, results from metabolic measures did not support this conclusion; both populations showed an increase in resting metabolic rate and a decrease of aerobic scope in fresh water. Similarly, excess post exercise oxygen consumption was higher for both populations in fresh than in brackish water. While swimming results suggest that environmentally dependent performance differences may be a result of selection in divergent osmotic environments, the differences between populations are not coupled with divergence in metabolic performance. PMID- 26880280 TI - Integrating Time-Varying and Ecological Exposures into Multivariate Analyses of Hospital-Acquired Infection Risk Factors: A Review and Demonstration. AB - OBJECTIVES Hospital-acquired infections (HAIs) develop rapidly after brief and transient exposures, and ecological exposures are central to their etiology. However, many studies of HAIs risk do not correctly account for the timing of outcomes relative to exposures, and they ignore ecological factors. We aimed to describe statistical practice in the most cited HAI literature as it relates to these issues, and to demonstrate how to implement models that can be used to account for them. METHODS We conducted a literature search to identify 8 frequently cited articles having primary outcomes that were incident HAIs, were based on individual-level data, and used multivariate statistical methods. Next, using an inpatient cohort of incident Clostridium difficile infection (CDI), we compared 3 valid strategies for assessing risk factors for incident infection: a cohort study with time-fixed exposures, a cohort study with time-varying exposures, and a case-control study with time-varying exposures. RESULTS Of the 8 studies identified in the literature scan, 3 did not adjust for time-at-risk, 6 did not assess the timing of exposures in a time-window prior to outcome ascertainment, 6 did not include ecological covariates, and 6 did not account for the clustering of outcomes in time and space. Our 3 modeling strategies yielded similar risk-factor estimates for CDI risk. CONCLUSIONS Several common statistical methods can be used to augment standard regression methods to improve the identification of HAI risk factors. Infect. PMID- 26880281 TI - Social media and gamification: Engaging vulnerable parents in an online evidence based parenting program. AB - The aim of this study was to examine the feasibility (accessibility, engagement and impact) of adding social media and gaming features (e.g., social sharing with anonymity, badges to incentivize skills practice, an accredited facilitator for support) and access via smartphones to an evidenced-based parenting program, Triple P Online. The highly vulnerable population included 155 disadvantaged, high-risk parents (e.g., 76% had a family annual income of less than $15,000; 41% had been incarcerated; 38% were in drug/alcohol treatment; and 24% had had a child removed due to maltreatment). The ethnic groups most commonly identified were African American (24%) and Hispanic (66%). Respondents were primarily mothers (86%) from five community programs in Los Angeles. The study used a single group repeated measures design (pre, post, 6-month follow-up). Data collected included standardized self-report measures, post-intervention focus groups and interviews, website usage reports, and Google Analytics. Significant multivariate ANOVA time effects were found, demonstrating reductions in child behavioral problems, reduced lax/permissive and over-reactive parenting, and decreased parental stress. No effects were found for parental confidence, attributions, or depression and anxiety (which were in the normal range at baseline). Positive effects were maintained or improved at 6-month follow-up. The participants engaged in the online community and valued its flexibility, anonymity, and shared learning. This foundational implementation trial provides support for future rigorous evaluation of social media and gaming features as a medium for increasing parental engagement in evidence-based parenting programs online--a public health approach to protect and improve the development of vulnerable children. PMID- 26880282 TI - Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy. AB - OBJECTIVE: The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. METHODS: All patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, The Netherlands, who were on CSII therapy between 2000 and 2011 were selected for inclusion. All data as recorded during outpatient visits were retrospectively collected from patients' charts. Analyses were performed using R Statistical Software. RESULTS: Data of 847 outpatient visits of 78 patients [31 males (39.7%) and 47 females (60.3%)] were analyzed. Mean age at diagnosis was 7.1 +/- 3.7 yr, mean age at start of pump therapy 10.1 +/- 3.8 yr. Mean HbA1c before pump start was 8.3 +/- 1.0%, median BMI standard deviation score for age and gender was 0.64 (-1.89-3.79). Median follow-up time per patient was 29 months with an average of 10 visits (range: 3-25). Multivariate analysis revealed that a change of 10% in %BD/T resulted in a decrease or increase of HbA1c of 0.22% [95% confidence interval (CI): 0.15-0.29). No significant effect was observed from SDS BMI, sex, or duration of diabetes. CONCLUSION: Low dose basal insulin infusion as a percentage of total insulin dose has a positive effect on metabolic outcome as expressed in HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. This supports the tendency to aim at the lowest basal insulin requirements in pump setting strategy. PMID- 26880283 TI - Senator questions pain panel's ties to industry. PMID- 26880284 TI - The Short-Term Longitudinal and Reciprocal Relations Between Peer Victimization on Facebook and Adolescents' Well-Being. AB - Although studies have shown that depressive symptoms, life satisfaction, and adolescents' online peer victimization are associated, there remain critical gaps in our understanding of these relationships. To address these gaps, the present two-wave panel study (N Time1 = 1840) (1) examines the short-term longitudinal and reciprocal relationships between peer victimization on Facebook, depressive symptoms and life satisfaction during adolescence, and (2) explores the moderating role of adolescents' gender, age, and perceived friend support. Self report data from 1621 adolescent Facebook users (48 % girls; M Age = 14.76; SD = 1.41) were used to test our hypotheses. The majority of the sample (92 %) was born in Belgium. Cross-lagged analyses indicated that peer victimization on Facebook marginally predicted decreases in life satisfaction, and life satisfaction predicted decreases in peer victimization on Facebook. However, depressive symptoms were a risk factor for peer victimization on Facebook, rather than an outcome. In addition, support from friends protected adolescents from the harmful outcomes of peer victimization on Facebook. Both theoretical and practical implications are discussed. PMID- 26880285 TI - Does Media Literacy Mitigate Risk for Reduced Body Satisfaction Following Exposure to Thin-Ideal Media? AB - Exposure to thin-ideal media can contribute to increased body dissatisfaction in adolescent girls. Understanding the factors that may prevent or exacerbate the negative effects of media exposure on body dissatisfaction is important to facilitate prevention of these problems. This study evaluated the effects of exposure to thin-ideal media images on body image in three instructional set experimental conditions: appearance comparison, peer norms, and control. An important aim was to examine baseline levels of media literacy as a protective factor and trait thin-ideal internalization and trait upward appearance comparison as risk factors. Early adolescent girls (N = 246) completed baseline measures and 1 week later viewed thin-ideal media images, before and after which they rated their state body satisfaction. Participants in the appearance comparison instruction but not peer norms instruction condition had significantly reduced body satisfaction. Media literacy, particularly high levels of critical thinking, mitigated the negative effects of trait thin-ideal internalization and trait upward appearance comparison on body satisfaction outcomes. These findings provide evidence for the role of media literacy as a protective factor against the negative effects on body satisfaction of exposure to thin-ideal media images, and also provide evidence to support the development and implementation of media literacy-based body image interventions. PMID- 26880286 TI - Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP. AB - BACKGROUND: Nonphotosensitive trichothiodystrophy (TTDN) is a rare autosomal recessive disorder of neuroectodermal origin. The condition is marked by hair abnormalities, intellectual impairment, nail dystrophies and susceptibility to infections but with no UV sensitivity. METHODS: We identified three consanguineous Pakistani families with varied TTDN features and used homozygosity mapping, linkage analysis, and Sanger and exome sequencing in order to identify pathogenic variants. Haplotype analysis was performed and haplotype age estimated. A splicing assay was used to validate the effect of the MPLKIP splice variant on expression. RESULTS: Affected individuals from all families exhibit several TTDN features along with a heart-specific feature, i.e. mitral regurgitation. Exome sequencing in the probands from families ED168 and ED241 identified a homozygous splice mutation c.339 + 1G > A within MPLKIP. The same splice variant co-segregates with TTDN in a third family ED210. The MPLKIP splice variant was not found in public databases, e.g. the Exome Aggregation Consortium, and in unrelated Pakistani controls. Functional analysis of the splice variant confirmed intron retention, which leads to protein truncation and loss of a phosphorylation site. Haplotype analysis identified a 585.1-kb haplotype which includes the MPLKIP variant, supporting the existence of a founder haplotype that is estimated to be 25,900 years old. CONCLUSION: This study extends the allelic and phenotypic spectra of MPLKIP-related TTDN, to include a splice variant that causes cardiomyopathy as part of the TTDN phenotype. PMID- 26880288 TI - Secondary metabolites of seagrasses (Alismatales and Potamogetonales; Alismatidae): Chemical diversity, bioactivity, and ecological function. AB - Seagrasses are the only higher plants living in fully marine environments; they play a significant role in coastal ecosystems. Seagrasses inhabit the coastal shelves of all continents except Antarctica and can grow in depths of up to 90 m. Because of their eminent ecological importance, innumerous studies have been dedicated to seagrasses and their ecology. However, the phytochemistry has not been equally well investigated yet and many of the existing studies in chemical ecology are only investigating the chemistry at the level of compound classes, e.g. phenolics, and not at the level of chemically defined metabolites. In the present review, the existing literature on secondary metabolites of seagrasses, their known source seagrasses, their bioactivity, and ecological function are compiled and critically assessed. Moreover, research gaps are highlighted and avenues for future research are discussed. Currently, a total of 154 chemically defined natural products have been reported from the about 70 seagrass species known worldwide. Compounds reported include simple phenols derivatives (four compounds), phenylmethane derivatives (14 compounds), phenylethane derivatives (four compounds), phenylpropane derivatives including their esters and dimers (20 compounds), chalkones (four compounds), flavonoids including catechins (57 compounds), phenylheptanoids (four compounds), one monoterpene derivative, one sesquiterpene, diterpenoids (13 compounds), steroids (31 compounds), and one alkaloid. Most of the existing bioactivity studies of seagrass metabolites and extracts have been directed to potential cytotoxic, antimicrobial, or antimacrofouling activity. Antimicrobial studies have been performed towards panels of both human pathogens and ecologically relevant pathogens. In the antimacrofouling studies, investigations of the potential of zosteric acid from the genus Zostera are the most numerous and have yielded so far the most interesting results. Studies on the chemical ecology of seagrasses often have been focused on variation in phenolic compounds and include but are not limited to studies on variation due to abiotic factors, seasonal variation, variation in response to grazing by fish or sea urchins, or following microbial attack. PMID- 26880287 TI - Toxigenic profile of methicillin-sensitive and resistant Staphylococcus aureus isolated from special groups. AB - BACKGROUND: Staphylococcus aureus is characterized by its pathogenicity and high prevalence, causing disease in both healthy and immunocompromised individuals due to its easy dissemination. This fact is aggravated by the widespread dissemination of S. aureus carrying toxigenic genes. The objective of this study was to determine the toxigenic profile of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in patients with purulent skin and/or soft tissue infections seen at the Dermatology Department of the University Hospital of the Botucatu Medical School, asymptomatic adults older than 60 years living in nursing homes, and prison inmates of the Avare Detention Center. METHODS: PCR was used for the detection of the mecA gene, enterotoxin genes (sea, seb, and sec), exfoliative toxins A and B (eta and etb), toxic shock syndrome toxin 1 (tst), panton-valentine leukocidin (lukS-PV and lukF-PV), and alpha- and delta-hemolysins or cytotoxins (hla and hld). RESULTS: The results showed a significant prevalence of toxigenic genes among S. aureus isolates from asymptomatic individuals, with the observation of a higher prevalence of cytotoxin genes. However, the panton-valentine leukocidin gene was only detected in MSSA isolated from patients with skin infections and the tst gene was exclusively found in MSSA isolated from prison inmates. CONCLUSIONS: The present study demonstrated a significant prevalence of toxigenic genes in MSSA and MRSA strains isolated from asymptomatic S. aureus carriers. There was a higher prevalence of cytotoxin genes. PMID- 26880289 TI - Identification and characterization of two bisabolene synthases from linear glandular trichomes of sunflower (Helianthus annuus L., Asteraceae). AB - Sunflower is known to produce a variety of bisabolene-type sesquiterpenes and accumulates these substances in trichomes of leaves, stems and flowering parts. A bioinformatics approach was used to identify the enzyme responsible for the initial step in the biosynthesis of these compounds from its precursor farnesyl pyrophosphate. Based on sequence similarity with a known bisabolene synthases from Arabidopsis thaliana AtTPS12, candidate genes of Helianthus were searched in EST-database and used to design specific primers. PCR experiments identified two candidates in the RNA pool of linear glandular trichomes of sunflower. Their sequences contained the typical motifs of sesquiterpene synthases and their expression in yeast functionally characterized them as bisabolene synthases. Spectroscopic analysis identified the stereochemistry of the product of both enzymes as (Z)-gamma-bisabolene. The origin of the two sunflower bisabolene synthase genes from the transcripts of linear trichomes indicates that they may be involved in the synthesis of sesquiterpenes produced in these trichomes. Comparison of the amino acid sequences of the sunflower bisabolene synthases showed high similarity with sesquiterpene synthases from other Asteracean species and indicated putative evolutionary origin from a beta-farnesene synthase. PMID- 26880290 TI - Prenylated phenyl polyketides and acylphloroglucinols from Hypericum peplidifolium. AB - In search for new or chemo-taxonomically relevant bioactive compounds from chemically unexplored Hypericum species, four previously undescribed natural products, named peplidiforones A-D were isolated and characterized from Hypericum peplidifolium A. Rich., together with six known compounds. The structures of all compounds were elucidated by extensive 1D- and 2D-NMR experiments, high resolution mass spectrometric analyses (HR-MS), and by comparison with data reported in the literature. Seven of these compounds are phenyl polyketides while three are acylphloroglucinol type compounds. Peplidiforone C, which possesses an unusual carbon skeleton consisting of a furan ring substituted by a 2,2 dimethylbut-3-enoyl moiety, is the first example of a prenylated furan derivative isolated from the genus Hypericum. The cytotoxicity, antifungal, and anti-herpes simplex virus type 1 (HSV-1) activities of extracts and compounds are described. PMID- 26880292 TI - Kawasaki disease and cardiovascular risk: a comprehensive review of subclinical vascular changes in the longer term. AB - Studies of subclinical vascular changes post-Kawasaki disease indicate that, in general, individuals with a history of coronary artery aneurysms have increased carotid intima-media thickness, evidence of endothelial dysfunction, and increased arterial stiffness, possibly indicative of heightened cardiovascular risk. The results are less consistent for low-risk groups. CONCLUSION: Until data are available from larger prospective studies, it is prudent to advise families of individuals with a history of Kawasaki disease to minimise traditional modifiable cardiovascular risk factors. PMID- 26880293 TI - Solvent-Dependent Structure of Iridium Dihydride Complexes: Different Geometries at Low and High Dielectricity of the Medium. AB - The hydride iridium pincer complex [(PCyP)IrH2] (PCyP=cis-1,3-bis[(di-tert butylphosphino)methyl]cyclohexane, 1) reveals remarkably solvent-dependent hydride chemical shifts, isotope chemical shifts, JHD and T1(min), with rHH increasing upon moving to more polar medium. The only known example of such behaviour (complex [(POCOP)IrH2], POCOP=2,6-(tBu2PO)2C6H3) was explained by the coordination of a polar solvent molecule to the iridium (J. Am. Chem. Soc. 2006, 128, 17114). Based on the existence of an agostic bond between alpha-C-H and iridium in 1 in all solvents, we argue that the coordination of solvent can be rejected. DFT calculations revealed that the structures of 1 and [(POCOP)IrH2] depend on the dielectric permittivity of the medium and these compounds adopt trigonal-bipyramidal geometries in non-polar media and square-pyramidal geometries in polar media. PMID- 26880294 TI - Primary upper extremity deep vein thrombosis: Clinical characteristics and outcome according to the presence of thoracic outlet syndrome. PMID- 26880295 TI - Heterogeneity of the prognostic significance of B-type natriuretic peptide levels on admission in patients hospitalized for acute heart failure syndromes. AB - BACKGROUND: We hypothesized that variation in baseline characteristics of patients with acute heart failure syndromes (AHFS) affects the prognostic significance of B-type natriuretic peptide (BNP) levels because of heterogeneity of this patient population. We evaluated the association of elevated BNP levels on admission with an increased risk of adverse clinical outcomes in subgroups of patients hospitalized for AHFS. METHODS: This study included patients from the acute decompensated heart failure syndromes (ATTEND) study, a multicenter prospective cohort of 4501 AHFS patients with BNP data on admission. RESULTS: The geometric mean BNP level was 654.9pg/mL (95% confidence interval: 636.1-674.2), and the optimal cut-off value for all-cause death was 1157pg/mL. All-cause mortality after admission was significantly higher in patients with high BNP levels (>1157pg/mL) than in those with low BNP levels (<=1157pg/mL) (median follow-up: 508days, log-rank P<0.001). Subgroup analyses were performed to evaluate the heterogeneity of the prognostic significance of BNP levels. The effect of high BNP levels on the risk of all-cause mortality was significantly greater in the subgroup of patients with a non-hypertensive etiology, low creatinine levels (<1.3mg/dL), and high sodium levels (>=135mEq/L) than in those without these factors (P=0.024, P<0.001, and P<0.001 for the interaction, respectively). CONCLUSIONS: The present analysis shows that underlying etiology of heart failure (i.e., hypertensive), renal function, and sodium levels should be considered for assessing the clinical significance of elevated BNP levels on admission in relation to the risk of adverse outcome after hospitalization for AHFS. PMID- 26880296 TI - Where do people live longer and shorter lives? An ecological study of old-age survival across 4404 small areas from 18 European countries. AB - BACKGROUND: Further increases in life expectancy in high-income countries depend to a large extent on advances in old-age survival. We aimed to characterise the spatial distribution of old-age survival across small areas of Europe, and to identify areas with significantly high or low survivorship. METHODS: This study incorporated 4404 small areas from 18 European countries. We used a 10-year survival rate to express the proportion of population aged 75-84 years who reached 85-94 years of age (beyond average life expectancy). This metric was calculated for each gender using decennial census data (1991, 2001 and 2011) at small geographical areas. To address problems associated with small areas, rates were smoothed using a Bayesian spatial model. Excursion sets were defined to identify areas with significantly high (>95th centile) and low (<5th) survival. RESULTS: In 2011, on average, 47.1% (range: 22.5-71.5) of the female population aged 75-84 years had reached 85-94 years of age, compared to 34.2% (16.4-49.6) of the males. These figures, however, hide important and time-persistent spatial inequalities. Higher survival rates were concentrated in northern Spain, Andorra and northeastern Italy, and in the south and west of France. Lower survival was found in parts of the UK, Scandinavia and the Netherlands, and in some areas of southern Europe. Within these regions, we detected areas with significantly high and low old-age survival. CONCLUSIONS: Clear and persistent spatial inequalities in old-age survival exist, suggesting that European social unity is still to be accomplished. These inequalities could arise from a myriad of population health determinants (eg, poverty, unhealthy lifestyles), which merit further study. PMID- 26880297 TI - Facile synthesis of flexible macroporous polypropylene sponges for separation of oil and water. AB - Oil spill disasters always occur accidentally, accompanied by the release of plenty of crude oil that could spread quickly over a wide area, creating enormous damage to the fragile marine ecological system. Therefore, the facile large-scale synthesis of hydrophobic three-dimensional (3-D) porous sorbents from low cost raw materials is in urgent demand. In this study, we report the facile template free synthesis of polypropylene (PP) sponge by using a thermally-induced phase separation (TIPS) technique. The obtained sponge showed macroporous structure, excellent mechanical property, high hydrophobicity, and superoleophilicity. Oil could be separated from an oil/water mixture by simple immersing the sponge into the mixture and subsequent squeezing the sponge. All of these features make this sponge the most promising oil sorbent that will replace commercial non-woven PP fabrics. PMID- 26880299 TI - Predictive value of PI-RADS classification in MRI-directed transrectal ultrasound guided prostate biopsy. AB - AIM: To correlate the results of transrectal ultrasound (TRUS)-guided targeted prostate biopsies (performed in the setting of at least one previous negative biopsy) with the Prostate Imaging Reporting and Data System (PI-RADS). MATERIAL AND METHODS: Fifty-two patients (mean age 64 years, range 52-76 years), with previous negative prostate biopsy underwent magnetic resonance imaging (MRI) directed TRUS-guided targeted and sectoral biopsy. A retrospective review of MRI examinations was carried out, blinded to biopsy results. PI-RADS scores (T2, diffusion-weighted imaging [DWI] and overall) were assigned on a per lesion basis, and localised to sextants. The scores were correlated with biopsy results, and the positive predictive values (PPV) of PIRADS scores for positive biopsies were calculated. RESULTS: Overall, biopsies were positive in 23/52 (44.2%) patients. Eighty-one areas were targeted in 52 patients. On a per lesion basis, there was significant correlation between positive targeted biopsy and both T2 and overall PI-RADS score (p<0.001). The correlation between biopsy and DWI score was significant for peripheral zone tumours only, not for transitional zone tumours. The PPV of overall PI-RADS scores of 3, 4, and 5 were 10.6%, 44%, and 100%, respectively. The PPV of T2 PI-RADS scores of 3, 4, and 5 were 19.6%, 60%, and 100%, respectively. The PPV of DWI PI-RADS scores of 3, 4, and 5 were 50%, 27.3%, and 33%, respectively. When transitional tumours were excluded, the PPV of DWI PI-RADS 3, 4, and 5 were 40%, 43%, and 78%. CONCLUSION: The PIRADS score provides an effective framework for determining the likelihood of prostate cancer on MRI. The DWI PI-RADS score correlates well with the presence of peripheral zone tumour on targeted biopsy, but not with transitional zone tumours. PMID- 26880298 TI - Timing of excision after a non-severe burn has a significant impact on the subsequent immune response in a murine model. AB - BACKGROUND: Burn excision has emerged as the dominant clinical paradigm in treatment of deep burns. Surgical intervention is common but the timing of wound excision is a balance between wound depth assessment, avoidance of infection and unnecessary intervention. However the physiological impact of timing of excision and consequences for the immune response are not well understood. METHODS: Mice were subject to full-thickness burn (<8% TBSA) followed by early (day 1) or late (day 8) surgical excision. Draining lymph nodes, wound tissue and sera were collected longitudinally at day 2 and day 6 after excision and analyzed for cytokine, dendritic cell and T cell profiles using FACS and multiplex ELISA assays. RESULTS: Delayed excision after injury initiated acute and severe inflammatory responses, with high levels of inflammatory cytokines, increased chemokine responses, and elevated Th2 promoting cytokines compared to early excision. Cellular inflammation in the wound was exacerbated with elevated neutrophils, eosinophil and monocytes. Wound cellular innate immune response decreased after late excision with a loss of inflammatory dendritic cells (DC), decreased NKT cells, and inhibition of NK cell activation. Systemically late excision increased trafficking conventional CD8alpha(-) DC to the lymph node, but there was no apparent DC activation. This was reflected in the induction of CD4T regulatory (Treg) cells and suppression of CD8T cell proliferation after late excision. No suppression was observed with early excision. CONCLUSION: This data suggests early excision of the wound, during the phase of immune down-regulation initiated by the burn, maintains an innate and adaptive immune cell response. In contrast, late wound excision induced a severe inflammatory response, with subsequent down-regulation of innate and adaptive immune cell responses. Therefore timing of excision is critical in affecting the immune response to burn. PMID- 26880300 TI - An advanced bioinformatics approach for analyzing RNA-seq data reveals sigma H dependent regulation of competence genes in Listeria monocytogenes. AB - BACKGROUND: Alternative sigma factors are important transcriptional regulators in bacteria. While sigma(B) has been shown to control a large regulon and play important roles in stress response and virulence in the pathogen Listeria monocytogenes, the function of sigma(H) has not yet been well defined in Listeria, even though sigma(H) controls a large regulon in the closely related non-pathogenic Bacillus subtilis. RESULTS: Using RNA-seq characterization of a L. monocytogenes strain with deletions of all 4 genes encoding alternative sigma factors (DeltaBCHL), which was further modified to overexpress sigH (DeltaBCHL::P rha -sigH), we identified 6 transcription units (TUs) that are transcribed from sigma(H)-dependent promoters. Five of these TUs had not been previously identified. Identification of these promoters was facilitated by use of a bio informatics approach that compared normalized RNA-seq coverage (NRC), between DeltaBCHL::P rha -sigH and a DeltaBCHL control, using sliding windows of 51 nt along the whole genome rather than comparing NRC calculated only for whole genes. Interestingly, we found that three operons that encode competence genes (comGABCDEFG, comEABC, coiA) are transcribed from sigma(H)-dependent promoters. While these promoters were highly conserved in L. monocytogenes, none of them were found in all Listeria spp. and coiA and its sigma(H)-dependent promoter were only found in L. monocytogenes. CONCLUSIONS: Our data indicate that a number of L. monocytogenes competence genes are regulated by sigma(H). This sigma(H) dependent regulation of competence related genes is conserved in the pathogen L. monocytogenes, but not in other non-pathogenic Listeria strains. Combined with prior data that indicated a role of sigma(H) in virulence in a mouse model, this suggests a possible novel role of sigma(H)-dependent competence genes in L. monocytogenes virulence. Development and implementation of a sliding window approach to identify differential transcription using RNA-seq data, not only allowed for identification of sigma(H)-dependent promoters, but also provides a general approach for sensitive identification of differentially transcribed promoters and genes, particularly for genes that are transcribed from multiple promoter elements only some of which show differential transcription. PMID- 26880301 TI - Genetic dissection of plant architecture and yield-related traits in Brassica napus. AB - An optimized plant architecture (PA) is fundamental for high-yield breeding but the genetic control of the important trait is largely unknown in rapeseed. Here plant architecture factors (PAFs) were proposed to consist of main inflorescence length proportion (MILP), branch height proportion (BHP), and branch segment proportion (BSP). Comparison of different genotypes in a DH population grown in diverse environments showed that an optimized PAF performance with MILP and BHP between 0.3-0.4 was important for high yield potential. In total, 163 unique quantitative trait loci (QTLs) for PA- and plant yield (PY)-related traits were mapped onto a high-density genetic map. Furthermore, 190 PA-related candidate genes for 91 unique PA QTLs and 2350 PY epistatic interaction loci-pairs were identified, which explain 2.8-51.8% and 5.2-23.6% of phenotypic variation, respectively. Three gene categories, transcription factor, auxin/IAA, and gibberellin, comprise the largest proportions of candidate genes for PA-related QTLs. The effectiveness of QTL candidate genes prediction was demonstrated by cloning of three candidate genes, Bna.A02.CLV2, Bna.A09.SLY2, and Bna.C07.AHK4. The study thus outlines a gene network for control of PA-related traits and provides novel information for understanding the establishment of ideal PA and for developing effective breeding strategies for yield improvement in rapeseed and other crops. PMID- 26880302 TI - Atherogenicity of postprandial hyperglycemia and lipotoxicity. AB - Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose regulation. However, physicians continue to rely on fasting plasma glucose and glycated hemoglobin to guide management. There is a linear relationship between the risk of cardiovascular death and the 2-h oral glucose tolerance test, while a study confirms postprandial hyperglycemia as independent risk factor for cardiovascular disease in type 2 diabetes. At the same time, several studies show that postprandial hypertriglyceridemia may also be a cardiovascular risk factor. Interestingly, the simultaneous presence of postprandial hyperglycemia and postprandial hypertriglyceridemia has an additive effect in worsening endothelial function and inflammation. Evidence supports the hypothesis glucose postprandial hyperglycemia and hypertriglyceridemia may favor the appearance of the cardiovascular disease through the generation of an oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycemia is a common phenomenon even in patients who may be considered in "good metabolic control". Therefore, physicians should consider monitoring and targeting postprandial plasma glucose, as well as glycated hemoglobin and fasting plasma glucose, in patients with type 2 diabetes. PMID- 26880304 TI - 2-Methoxyestradiol prevents monocyte adhesion to vascular endothelial cells via downregulation of VCAM-1 expression. AB - 2-Methoxyestradiol (2-ME) reduces atherosclerotic lesion formation. However, the underlying mechanisms remain largely unknown. In this work, we investigated the effect of 2-ME on monocyte adhesion to vascular endothelial cells. Lipopolysaccharides (LPS) greatly increased the attachment of monocyte onto cultured human umbilical vascular endothelial cells (HUVECs), which was inhibited by 2-ME in a dose- and time-dependent manner, or by the vascular cell adhesion protein-1 (VCAM-1) neutralizing antibody, suggesting that a functional releationship between 2-ME and VCAM-1 may exist. In accordance with this, treatment with 2-ME (10(-)(7)-10(-)(5) M) for 6-48 h downregulated VCAM-1 protein expression. Meanwhile, the nuclear factor kappaB (NF-kappaB) p65 subunit activity and its nuclear translocation was inhibited by 2-ME in HUVECs. The PI3K inhibitor wortmannin or the specific Akt siRNA both inhibited the effects of 2-ME, suggesting that 2-ME inhibited p65 activity via PI3K/Akt signaling. In conclusion, 2-ME inhibits VCAM-1 expression and thus prevents monocyte adhesion to vascular endothelial cells via regulation of PI3K/Akt and NF-kappaB signaling. These findings will be helpful for better understanding the mechanisms through which 2-ME improves endothelial function. PMID- 26880305 TI - Central Pain Following Cord Severance for Cephalosomatic Anastomosis. AB - One of the key obstacles to a successful head transplant is the possible onset of central pain, a chronic pain condition that would impair the quality of life of the transplantee. In this review, we provide the reader with a knowledge of this neglected aspect of the head transplant initiative and outline the management should this eventuality occur. PMID- 26880303 TI - Methodological issues in human studies of endocrine disrupting chemicals. AB - Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half lives among populations with a relatively low exposure dose range of exposure can likely produce relatively more reliable results, because the measurement of EDCs with long half-lives likely represents typical long-term exposure and populations with exposure in the low range of doses are likely to have a reference group closer to non-exposure. PMID- 26880308 TI - Structural analysis of ruthenium-arene complexes using ion mobility mass spectrometry, collision-induced dissociation, and DFT. AB - Ion mobility mass spectrometry (IM-MS) and collision-induced dissociation (CID) techniques were used to investigate the influence of the phosphine ligand on the physicochemical properties of [RuCl2(p-cymene)(PCy3)] (), [RuCl2(p-cymene)(PPh3)] (), and [RuCl2(p-cymene)(PTA)] () in the gas phase (PTA is 1,3,5-triaza-7 phosphaadamantane). Electrospray ionization of complexes and led to the corresponding [RuCl(p-cymene)(PR3)](+) ions via the dissociation of a chlorido ligand, whereas RAPTA-C () afforded two molecular ions by in-source oxidation ([Ru(III)Cl2(p-cymene)(PTA)](+)) or protonation ([RuCl2(p-cymene)(PTA+H)](+)). Control experiments showed that the balance between these two ionization paths was strongly influenced by the nature of the solvent used for infusion. Collision cross sections (CCSs) of the four molecular ions accurately reflected the variations of steric bulk inferred from the Tolman steric parameters (theta) of the phosphine ligands. Moreover, DFT calculations combined with a model based on the kinetic theory of gases (the trajectory method of the IMoS software) afforded reliable CCS predictions. The almost two times higher dipole moment of [RuCl2(p cymene)(PTA+H)](+) (MU = 13.75 D) compared to [Ru(III)Cl2(p-cymene)(PTA)](+) (MU = 7.18 D) was held responsible for increased ion-induced dipole interactions with a polarizable drift gas such as N2. Further experiments with He and CO2 confirmed that increasing the polarizability of the buffer gas improved the separation between the two molecular ions derived from complex . The fragmentation patterns of complexes were determined by CID. The sequence of collision voltages at which 50% of a precursor ion dissociates (V50) recorded for the molecular ions derived from compounds was in good agreement with simple electronic considerations based on the donor strength of the phosphine ligand. Thus, the CCS and V50 parameters used to determine the shape and stability of ionic species in the gas phase are complementary to the Tolman steric and electronic parameters (theta and TEP) commonly used by organometallic chemists in condensed phases. PMID- 26880307 TI - Patient outcomes following second surgery for recurrent glioblastoma. AB - BACKGROUND: The most appropriate management of recurrent glioblastoma is still controversial. In particular, the role of surgery at recurrence remains uncertain. PATIENTS & METHODS: From our Institutional data warehouse we analyzed 270 consecutive patients who received second surgery for recurrent glioblastoma, to assess survival after second surgery, and to evaluate prognostic factors. RESULTS: Complete resection was found in 128 (47.4%) and partial resection in 142 patients (52.6%). Median survival from second surgery was 11.4 months (95% CI: 10.0-12.7). Multivariate analysis showed that age (p = 0.001), MGMT methylation (p = 0.021) and extent of surgery (p < 0.001) are associated with better survival. CONCLUSION: A complete resection should be the goal for second resection and younger age and MGMT methylation status might be considered in the selection of patients. PMID- 26880309 TI - [Towards new therapeutic concepts to fight against chronic hepatitis B]. PMID- 26880306 TI - Transferrin Receptor Controls AMPA Receptor Trafficking Efficiency and Synaptic Plasticity. AB - Transferrin receptor (TFR) is an important iron transporter regulating iron homeostasis and has long been used as a marker for clathrin mediated endocytosis. However, little is known about its additional function other than iron transport in the development of central nervous system (CNS). Here we demonstrate that TFR functions as a regulator to control AMPA receptor trafficking efficiency and synaptic plasticity. The conditional knockout (KO) of TFR in neural progenitor cells causes mice to develop progressive epileptic seizure, and dramatically reduces basal synaptic transmission and long-term potentiation (LTP). We further demonstrate that TFR KO remarkably reduces the binding efficiency of GluR2 to AP2 and subsequently decreases AMPA receptor endocytosis and recycling. Thus, our study reveals that TFR functions as a novel regulator to control AMPA trafficking efficiency and synaptic plasticity. PMID- 26880310 TI - [Denosumab: Lifetime treatment of osteoporosis?]. PMID- 26880311 TI - [Environmental medicine: Towards a COP21?]. PMID- 26880312 TI - Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer. AB - OBJECTIVE: To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using chi(2) , Kaplan Meier, and log-rank analyses. RESULTS: The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). CONCLUSIONS: This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted. PMID- 26880313 TI - Polycatechol nanosheet: a superior nanocarrier for highly effective chemo photothermal synergistic therapy in vivo. AB - The integration of phototherapy and chemotherapy in a single system holds great promise to improve the therapeutic efficacy of tumor treatment, but it remains a key challenge. In this study, we describe our recent finding that polycatechol nanosheet (PCCNS) can be facilely prepared on a large scale via chemical polymerization at 4 degrees C, as an effective nanocarrier for loading high density CuS nanocrystals as a photothermal agent. The resulting CuS/PCCNS nanocomposites exhibit good biocompatibility, strong stability, and a high photothermal conversion efficiency of ~45.7%. The subsequent loading of anticancer drug doxorubicin (Dox) creates a superior theranostic agent with pH- and heat-responsive drug release, leading to almost complete destruction of mouse cervical tumor under NIR laser irradiation. This development offers an attractive theranostic agent for in vivo chemo-photothermal synergistic therapy toward biomedical applications. PMID- 26880315 TI - Allocation of Residency Training Positions in Spain: Contextual Effects on Specialty Preferences. AB - In Spain's 'MIR' system, medical school graduates are ranked by their performance on a national exam and then sequentially choose from the available residency training positions. We took advantage of a unique survey of participants in the 2012 annual MIR cycle to analyze preferences under two different choice scenarios: the residency program actually chosen by each participant when it came her turn (the 'real') and the program that she would have chosen if all residency training programs had been available (the 'counterfactual'). Utilizing conditional logit models with random coefficients, we found significant differences in medical graduates' preferences between the two scenarios, particularly with respect to three specialty attributes: work hours/lifestyle, prestige among colleagues, and annual remuneration. In the counterfactual world, these attributes were valued preferentially by those nearer to the top, while in the real world, they were valued preferentially by graduates nearer to the bottom of the national ranking. Medical graduates' specialty preferences, which we conclude, are not intrinsically stable but depend critically on the 'rules of the game'. The MIR assignment system, by restricting choice, effectively creates an externality in which those at the bottom, who have fewer choices, want what those at the top already have. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26880314 TI - Tuftsin-driven experimental autoimmune encephalomyelitis recovery requires neuropilin-1. AB - Experimental autoimmune encephalomyelitis (EAE) is an animal model of demyelinating autoimmune disease, such as multiple sclerosis (MS), which is characterized by central nervous system white matter lesions, microglial activation, and peripheral T-cell infiltration secondary to blood-brain barrier disruption. We have previously shown that treatment with tuftsin, a tetrapeptide generated from IgG proteolysis, dramatically improves disease symptoms in EAE. Here, we report that microglial expression of Neuropilin-1 (Nrp1) is required for tuftsin-driven amelioration of EAE symptoms. Nrp1 ablation in microglia blocks microglial signaling and polarization to the anti-inflammatory M2 phenotype, and ablation in either the microglia or immunosuppressive regulatory T cells (Tregs) reduces extended functional contacts between them and Treg activation, implicating a role for microglia in the activation process, and more generally, how immune surveillance is conducted in the CNS. Taken together, our findings delineate the mechanistic action of tuftsin as a candidate therapeutic against immune-mediated demyelinating lesions. PMID- 26880316 TI - Engineering Plants for Geminivirus Resistance with CRISPR/Cas9 System. AB - The CRISPR/Cas9 system is an efficient genome-editing platform for diverse eukaryotic species, including plants. Recent work harnessed CRISPR/Cas9 technology to engineer resistance to geminiviruses. Here, we discuss opportunities, emerging developments, and potential pitfalls for using this technology to engineer resistance against single and multiple geminivirus infections in plants. PMID- 26880317 TI - Electrical Wiring and Long-Distance Plant Communication. AB - Electrical signalling over long distances is an efficient way of achieving cell to-cell communication in living organisms. In plants, the phloem can be considered as a 'green cable' that allows the transmission of action potentials (APs) induced by stimuli such as wounding and cold. Measuring phloem potential changes and separating them from secondary responses of surrounding tissues can be achieved using living aphids as bioelectrodes. Two glutamate receptor-like genes (GLR3.3 and 3.6) were identified as being involved in the propagation of electrical activity from the damaged to undamaged leaves. However, phloem APs are initiated and propagated independently of these glutamate receptors. Here, we propose new screening approaches to obtain further information on the components required for electrical signalling in phloem cables. PMID- 26880318 TI - Participation rates of childhood cancer survivors to self-administered questionnaires: a systematic review. AB - This review aimed to assess participation rates of childhood cancer survivors (CCS) invited to fill out a health-related questionnaire. Additionally, effects of study and CCS characteristics on participation rates were examined. PubMed, Web of Science, Ovid (EMBASE) and CINAHL databases were searched. Publications included were questionnaire-based studies among CCS diagnosed with cancer before the age of 21, alive at least 5 years past diagnosis and aged 16 years or older at the time of study. Thirty-five studies were included; the median participation rate was 65%. Sixteen studies reported information about CCS actively declining participation (median rate 5%). Five study characteristics seemed to influence participation rates: the use of reminders and incentives, the option to answer a shortened questionnaire, the recruitment of participants through their general practitioner and a pre-notification before sending out the questionnaire. Furthermore, CCS characteristics related to improved participation were female gender, Caucasian ethnicity and a higher educational level. The results of this study will help to improve the (methodological) quality of future questionnaire based studies among CCS, thereby increasing our knowledge about late effects among this group of survivors. PMID- 26880319 TI - Addressing the needs of people with disability in Nepal: The urgent need. AB - Health planners and policy makers often overlook the needs of people with disability (PWDs) in less developed countries such as Nepal. The aftermath of conflict and earthquake has further escalated the need of people with disability in Nepal. While the country is preparing for the implementation of a national health sector strategy for the next five years and when the health system is being restructured, we believe that this is the right time to address needs of people with disability by strengthening the health system and operationalizing community based rehabilitation. Furthermore, there is a need of a standard database and monitoring system to regularly assess social inclusion of people with disability. PMID- 26880320 TI - Evaluation of Inpatient Influenza and Pneumococcal Vaccination Acceptance Rates With Pharmacist Education. AB - OBJECTIVES: To detail the implementation of a pharmacist-driven education program targeting patients who originally declined pneumococcal or influenza vaccination upon hospital admission and to evaluate the results. METHODS: Patients admitted to a small community hospital who qualified to receive pneumococcal polysaccharide or influenza vaccination but declined upon admission were educated in person by pharmacists or pharmacy interns and reoffered vaccination. Patient education sheets were provided. Data were obtained via pharmacy intervention documentation in the pharmacy order entry system. Staff documented the outcome of counseling for each patient. RESULTS: A total of 214 and 83 patients receiving influenza and pneumococcal vaccination counseling, respectively, were evaluated. As a result, 23.4% ( P = .06) and 26.5% (n = 83, P = .18) of patients agreed to receive influenza and pneumococcal vaccines, respectively. An unanticipated subset of patients were undecided after counseling and wanted to consider the information further before making a final decision. Taken together with those who consented to receive the vaccine after counseling, 39.2% ( P = .001) and 45.8% ( P = .01) of patients were influenced by the influenza and pneumococcal vaccination counseling, respectively. CONCLUSION: Patient education performed by a pharmacist or pharmacy intern showed a trend toward increased pneumococcal and influenza vaccination acceptance rates for inpatients who had initially declined. PMID- 26880321 TI - Is Intimate Partner and Client Violence Associated with Condomless Anal Intercourse and HIV Among Male Sex Workers in Lima, Peru? AB - Violence experience can increase HIV risk behaviors; however, literature is scarce on violence among male sex workers (MSWs) globally. In 2014, 210 Peruvian MSWs (median age 24.9) were interviewed about their experience of physical, emotional, and sexual violence and condom use with non-paying intimate partners and clients and were tested for HIV. Multivariable models examined relationships between violence in the past 6 months, condomless anal intercourse (CLAI) in the past 3 months and HIV infection. HIV infection (24 %), CLAI (43 %), being a violence victim (42 %) and perpetrator (39 %) were common. In separate multivariable models, being a violence victim [adjusted prevalence ratio aPR = 1.49 (95 % CI 1.09-2.03)] and perpetrator [aPR = 1.39 (1.03-1.87)] were associated with CLAI. Further, being a victim [aPR = 1.65 (1.04-2.62)] was associated with HIV infection. Violence, which was significantly associated with CLAI and HIV infection, is common among Peruvian MSWs, reinforcing the importance of violence awareness and prevention as HIV risk-reduction strategies. PMID- 26880325 TI - Ciliary transcription factors in cancer--how understanding ciliogenesis can promote the detection and prognosis of cancer types. AB - Cilia play a plethora of roles in normal development and homeostasis as well as in disease. Their involvement in cell signalling processes and ability to inhibit cell cycle progression make them especially interesting subjects of investigation in the context of tumour formation and malignancy. Several key transcription factors regulate the transcriptional programme in cilia formation and some of these, eg RFX factors and FOXJ1, are implicated in cancer formation. Furthermore, RFX factors and FOXJ1 are increasingly being explored for their potential as markers to diagnose, classify and predict the outcome of cancers in patients, including recent work published in this journal on aggressive ependymoma and choroid plexus tumours. Here, some of the key findings and concepts on the roles of ciliary transcription factors in tumourigenesis are highlighted, and a brief perspective is given on how the investigation of ciliogenesis could contribute valuable tools for the diagnosis and prognosis of cancers. PMID- 26880324 TI - Pulmonary arterial hypertension associated with congenital heart disease: Comparison of clinical and anatomic-pathophysiologic classification. AB - BACKGROUND: Between 5% and 10% of patients with congenital heart disease (CHD) develop pulmonary arterial hypertension (PAH-CHD). Patients can be classified using either a clinical or anatomic-pathophysiologic system. No study has previously utilized both systems in a large cohort of patients. METHODS: Two hundred forty consecutive PAH-CHD patients diagnosed at a pulmonary hypertension referral center during 1995 to 2014 were identified from our unit database. Baseline characteristics, treatment and survival data were retrieved and survival analyses was performed. RESULTS: Both systems identified clear differences in baseline characteristics between subgroups. The anatomic-pathophysiologic system identified patients with post-tricuspid defects as having superior survival from point of referral to those with pre-tricuspid or complex defects (p < 0.05). Survival from point of referral was, however, not significantly different when patients were grouped using the clinical classification, although survival in all 4 groups was superior to that of 175 patients with idiopathic pulmonary arterial hypertension. Older age and higher creatinine, lower transfer factor of the lung for DLCO percent predicted and FEV1 percent predicted were independent adverse prognostic factors. CONCLUSION: Both PAH-CHD classification systems identified groups of patients distinct in terms of baseline characteristics. In our cohort, however, only the anatomic-pathophysiologic classification identified significantly different survival from point of referral. The presence of adverse prognostic markers may be useful in identifying patients requiring more aggressive pulmonary vascular therapy. PMID- 26880322 TI - Comparing Perceptions with Actual Reports of Close Friend's HIV Testing Behavior Among Urban Tanzanian Men. AB - Men have lower rates of HIV testing and higher rates of AIDS-related mortality compared to women in sub-Saharan Africa. To assess whether there is an opportunity to increase men's uptake of testing by correcting misperceptions about testing norms, we compare men's perceptions of their closest friend's HIV testing behaviors with the friend's actual testing self-report using a unique dataset of men sampled within their social networks (n = 59) in Dar es Salaam, Tanzania. We examine the accuracy and bias of perceptions among men who have tested for HIV (n = 391) and compare them to the perceptions among men who never tested (n = 432). We found that testers and non-testers did not differ in the accuracy of their perceptions, though non-testers were strongly biased towards assuming that their closest friends had not tested. Our results lend support to social norms approaches designed to correct the biased misperceptions of non testers to promote men's HIV testing. PMID- 26880327 TI - No association between fish consumption and risk of stroke in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain): a 13.8-year follow-up study. AB - OBJECTIVE: To prospectively assess the associations between lean fish, fatty fish and total fish intakes and risk of stroke in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). DESIGN: Fish intake was estimated from a validated dietary questionnaire. Cox proportional hazards regression models were used to assess the association between the intakes of lean fish, fatty fish and total fish and stroke risk. Models were run separately for men and women. SETTING: Five Spanish regions (Asturias, San Sebastian, Navarra, Granada and Murcia). SUBJECTS: Individuals (n 41 020; 15 490 men and 25 530 women) aged 20-69 years, recruited from 1992 to 1996 and followed up until December 2008 (December 2006 in the case of Asturias). Only participants with definite incident stroke were considered as cases. RESULTS: During a mean follow-up of 13.8 years, 674 strokes were identified and subsequently validated by record linkage with hospital discharge databases, primary-care records and regional mortality registries, comprising 531 ischaemic, seventy-nine haemorrhagic, forty-two subarachnoid and twenty-two unspecific strokes. After multiple adjustments, no significant associations were observed between lean fish, fatty fish and total fish consumption and the risk of stroke in men or women. In men, results revealed a non-significant trend towards an inverse association between lean fish (hazard ratio=0.84; 95 % CI 0.55, 1.29, P trend=0.06) and total fish consumption (hazard ratio=0.77; 95 % CI 0.51, 1.16, P trend=0.06) and risk of total stroke. CONCLUSIONS: In the EPIC-Spain cohort, no association was found between lean fish, fatty fish and total fish consumption and risk of stroke. PMID- 26880326 TI - APOBEC3B is an enzymatic source of molecular alterations in esophageal squamous cell carcinoma. AB - APOBEC3B belongs to the cytidine deaminase apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3) family of enzymes and induces C to T transitions of target DNA by cytidine deamination. Recently, several mutations in various cancers have been linked to APOBEC3B, suggesting a crucial role for this protein in carcinogenesis and cancer development. However, the significance of APOBEC3B in esophageal squamous cell carcinoma (ESCC) remains uncertain. In addition, the APOBEC3B immunoreactivity in cancer tissues is uncertain. Recently, we have demonstrated that PIK3CA mutation and the methylation level of long interspersed nucleotide element 1 (LINE-1) (a surrogate marker of global DNA methylation level) are prognostic markers and have crucial role on malignancy in ESCC patients. This study aims to clarify the impact of APOBEC3B on the clinical, pathological, and molecular features of ESCC. We evaluated APOBEC3B expression in ESCC and investigated the relationships among the immunoreactivity of APOBEC3B, clinical and pathological features, and the molecular features of ESCC (PIK3CA mutation, p53 expression, and LINE-1 methylation level). The immunoreactivity and mRNA level of APOBEC3B were significantly higher in cancer tissues than in noncancerous esophageal mucosae (P = 0.050). APOBEC3B expression was significantly correlated with PIK3CA mutation (P = 0.013), particularly with C to T transitions of PIK3CA (P = 0.041). Moreover, a high expression of APOBEC3B was significantly associated with LINE-1 hypomethylation (P = 0.027). Given the crucial roles of PIK3CA mutation and LINE-1 methylation levels, our findings might provide new insights into the biological mechanisms of ESCC tumorigenesis and progression. PMID- 26880328 TI - Clinical Outcomes and Costs Within 90 Days of Primary or Revision Total Joint Arthroplasty. AB - BACKGROUND: This study evaluated the factors and costs associated with discharge destination and readmission, within 90 days of surgery, for primary or revision total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: This retrospective database analysis used health care claims from the Truven MarketScan Database (2009-2013). Patients were selected if aged >=18 years, with continuous health plan enrollment from 3-month baseline through 3-month follow up. Logistic regression and Cox proportional hazard models were used to analyze factors associated with discharge destination and risk of readmission. Total 90 day costs were calculated for different patient pathways of care, dependent on complications, discharge destination, and readmission status. RESULTS: A total of 323,803 primary TKA, 25,354 revision TKA, 159,390 primary THA, and 17,934 revision THA cases met selection criteria. All-cause complications occurred in 2.5%, 37.2%, 2.6%, and 35.0% of each cohort. Complications, transfusions, and length of stay >=3 days were associated with greater odds of discharge to home with home health services or skilled nursing facility (SNF) vs home under self care (P < .001 all cohorts), whereas discharge to home with home health services or SNF was associated with greater risk of readmission (P < .05 for all cohorts except one). The ratio of total 90-day costs for the highest- (revision, SNF, readmission) vs lowest-cost (primary, home under self-care, no readmission) care pathways ranged from 1.8 to 2.2. CONCLUSION: As Medicare payment policy for total joint arthroplasty shifts toward bundling, an awareness of factors associated with outlier costs will be requisite to remain profitable. PMID- 26880329 TI - Systemic Metal Ion Levels in Patients With Modular-Neck Stems: A Prospective Cohort Study. AB - BACKGROUND: Recent registry data reveal that modular-neck hip prostheses are associated with increased revision rates compared to fixed-neck stems. Poor implant survival has been associated to corrosion at the neck-stem junction, inducing metal ion release and subsequently adverse local tissue reactions. Data on metal ion release on the neck-stem junction of such stems are scarce. The purpose of this study was to evaluate corrosion at this interface by determining metal ion release. METHODS: Serum and whole blood metal ion levels of 40 patients after 1 year of implantation of a modular-neck stem (titanium stem and cobalt chromium neck) were compared with 10 patients with a monobloc version of the stem (all titanium) and 10 patients having no implant at all. RESULTS: Seven of 40 patients (18%) with a modular-neck stem had cobalt or chromium concentrations >2 MUg/L. These patients underwent magnetic resonance imaging using metal artifact reduction sequences, which revealed a pseudotumor in 1 patient. CONCLUSION: Corrosion at the neck-stem junction of modular-neck stems is a reported phenomenon, which is in part reflected by elevated systemic ion levels. The use of such implants should be restricted to a minimum, and screening algorithms of patients with such implants must be developed. PMID- 26880330 TI - A Rhodium-Pentane Sigma-Alkane Complex: Characterization in the Solid State by Experimental and Computational Techniques. AB - The pentane sigma-complex [Rh{Cy2 P(CH2 CH2 )PCy2 }(eta(2) :eta(2) -C5 H12 )][BAr(F) 4 ] is synthesized by a solid/gas single-crystal to single-crystal transformation by addition of H2 to a precursor 1,3-pentadiene complex. Characterization by low temperature single-crystal X-ray diffraction (150 K) and SSNMR spectroscopy (158 K) reveals coordination through two Rh???H-C interactions in the 2,4-positions of the linear alkane. Periodic DFT calculations and molecular dynamics on the structure in the solid state provide insight into the experimentally observed Rh???H-C interaction, the extended environment in the crystal lattice and a temperature-dependent pentane rearrangement implicated by the SSNMR data. PMID- 26880331 TI - Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry. AB - OBJECTIVE: To report the contraceptive practices of women with epilepsy (WWE) in the community, predictors of highly effective contraception use, and reasons WWE provide for the selection of a particular method. METHODS: These cross-sectional data come from the Epilepsy Birth Control Registry (EBCR) web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We report demographic, epilepsy, and antiepileptic drug (AED) characteristics as well as contraceptive use. We determined the frequency of use of highly effective contraception use, that is, methods with failure rate <10%/year, and conducted binary logistic regression analysis to determine predictors of highly effective contraception use. We report frequencies of WWE who consult various health care providers regarding the selection of a method and the reasons cited for selection. RESULTS: Of the 796 WWE at risk of unintended pregnancy, 69.7% use what is generally considered to be highly effective contraception (hormonal, intrauterine device [IUD], tubal, vasectomy). Efficacy in WWE, especially for the 46.6% who use hormonal contraception, remains to be proven. Significant predictors of highly effective contraception use are insurance (insured 71.6% vs. noninsured 56.0%), race/ethnicity (Caucasian 71.3% vs. minority 51.0%), and age (38-47, 77.5%; 28-37, 71.8%; 18-27, 67.0%). Of the 87.2% who have a neurologist, only 25.4% consult them regarding selection of a method, although AED interaction is cited as the top reason for selection. SIGNIFICANCE: The EBCR web-based survey is the first large-scale study of the contraceptive practices of WWE in the community. The findings suggest a need for the development of evidence-based guidelines that address the efficacy and safety of contraceptive methods in this special population, and for greater discourse between neurologists and WWE regarding contraception. PMID- 26880332 TI - Person-centered older military veteran care when there are consequences. AB - The consequences of each war present themselves in many ways and differently within a veteran's lifetime. For civilian nurses to give applicable, vital care to the older veteran, they need to deeply appreciate the military culture, the strength of the ethos, as well as the various health concerns connected with the individual war/conflict. Attentiveness to the evolving health issues of older veterans are a priority at a time when many personal developmental changes are also creating life stressors for the Vietnam veterans and they are often presenting to civilian health facilities for their care. This article explores the controversial war within Vietnam (1955-1973), and the use of the universal question of "Have you ever served in the military?" An incremental veteran health assessment is discussed in order to care for the specific, prior-era physical/behavioral issues of post-traumatic stress disorder, Agent Orange, military sexual trauma, hepatitis C, and homelessness that are discussed for these men and women veterans, along with a rationale for their long-term presence, which is still evident today. Other relevant nursing interventions for veterans are suggested such as reminiscing, and art/animal-assisted therapy to supplement their medical care. PMID- 26880333 TI - The Densely O-Glycosylated MUC2 Mucin Protects the Intestine and Provides Food for the Commensal Bacteria. AB - All mucins are highly O-glycosylated by variable glycans depending on species, histoblood group and organ. This makes the intestinal main mucin MUC2 non degradable by the host digestive system but well by both commensal and pathogenic bacteria. The MUC2 glycans are important for selection of the commensal bacteria and act as a nutritional source for the bacteria; this also helps the host to recover some of the energy spent on constantly renewing the protective mucus layer. Glycosylation is the most diverse and common posttranslational modification of cell surfaces and secreted proteins. N-Glycosylation is most well studied and predictable, whereas O-glycosylation is more diverse and less well understood. O-Glycosylation is also often called mucin-type glycosylation as it is typical for mucins that often have more than 80% of the mass as O-glycans. This review will discuss the mucin-type O-glycosylation and especially the O glycosylation of human and mice intestinal mucin MUC2 in relation to bacteria and disease. PMID- 26880334 TI - High-Resolution Mapping of the Folding Transition State of a WW Domain. AB - Fast-folding WW domains are among the best-characterized systems for comparing experiments and simulations of protein folding. Recent microsecond-resolution experiments and long duration (totaling milliseconds) single-trajectory modeling have shown that even mechanistic changes in folding kinetics due to mutation can now be analyzed. Thus, a comprehensive set of experimental data would be helpful to benchmark the predictions made by simulations. Here, we use T-jump relaxation in conjunction with protein engineering and report mutational Phi-values (Phi(M)) as indicators for folding transition-state structure of 65 side chain, 7 backbone hydrogen bond, and 6 deletion and /or insertion mutants within loop 1 of the 34 residue hPin1 WW domain. Forty-five cross-validated consensus mutants could be identified that provide structural constraints for transition-state structure within all substructures of the WW domain fold (hydrophobic core, loop 1, loop 2, beta-sheet). We probe the robustness of the two hydrophobic clusters in the folding transition state, discuss how local backbone disorder in the native-state can lead to non-classical Phi(M)-values (Phi(M) > 1) in the rate-determining loop 1 substructure, and conclusively identify mutations and positions along the sequence that perturb the folding mechanism from loop 1-limited toward loop 2 limited folding. PMID- 26880336 TI - Modulation of helix stability of indolocarbazole-pyridine hybrid foldamers. AB - Through variation of the central pyridine in an indolocarbazole-pyridine hybrid foldamer, the kinetic stabilities of helical conformations were determined and compared based on the inter-conversion rates of P and M helical isomers. PMID- 26880337 TI - Current and future economic burden of diabetes among working-age adults in Asia: conservative estimates for Singapore from 2010-2050. AB - BACKGROUND: Diabetes not only imposes a huge health burden but also a large economic burden worldwide. In the working-age population, cost of lost productivity can far exceed diabetes-related medical cost. In this study, we aimed to estimate the current and future indirect and excess direct costs of diagnosed type 2 diabetes among the working-age population in Singapore. METHODS: A previously-published epidemiological model of diabetes was adapted to forecast prevalence among working-age patients with diagnosed type 2 diabetes in the absence of interventions. The current methodology of the American Diabetes Association was adopted to estimate the costs of diabetes for this population. Diabetes-related excess direct medical costs were obtained from a local cost study while indirect costs were calculated using the human capital approach applied to local labor force statistics. These cost were estimated conservatively from a societal perspective on a per patient basis and projected to the overall Singapore population from 2010 to 2050. RESULTS: In 2010, total economic costs per working-age patient were estimated to be US$5,646 (US$4,432-US$10,612), of which 42% were excess direct medical costs and 58% indirect productivity-related losses. Total cost is projected to rise to US$7,791 (US$5,741-US$12,756) in 2050, with the share of indirect costs rising to 65%. Simultaneous increases in prevalence imply that the total economic costs of diabetes for the entire working age population will increase by 2.4 fold from US$787 million in 2010 to US$1,867 million in 2050. CONCLUSIONS: By current projections, diabetes in Singapore represents a growing economic burden. Among the working-age population, the impact of productivity loss will become increasingly significant. Prevention efforts to reduce overall prevalence should also engage stakeholders outside the health sector who ultimately bear the indirect burden of disease. PMID- 26880338 TI - Chaetomium atrobrunneum and Aspergillus fumigatus in multiple tracheal aspirates: Copathogens or symbiosis. AB - Chaetomium atrobrunneum has never been reported to be associated with pneumonia. We report the isolation of C. atrobrunneum and Aspergillus fumigatus from a Chinese elderly patient with fatal pneumonia. Branched, long, and septate hyphae were observed in potassium hydroxide preparations and Gram-stained smears, and confluent C. atrobrunneum growth and a few A. fumigatus colonies were found in tracheal aspirates (nine separate occasions). These isolates were identified by conventional morphological methods and by sequencing the internal transcribed spacer and the D1/D2 domain of the 26S rRNA gene. The patient responded poorly to the combination therapy of amphotericin B and caspofungin. This report adds C. atrobrunneum to the list of fungal pneumonia in immunocompromised hosts. This case report also illustrated the presence of a growth symbiosis between Chaetomium species and A. fumigatus. PMID- 26880339 TI - Lazy workers are necessary for long-term sustainability in insect societies. AB - Optimality theory predicts the maximization of productivity in social insect colonies, but many inactive workers are found in ant colonies. Indeed, the low short-term productivity of ant colonies is often the consequence of high variation among workers in the threshold to respond to task-related stimuli. Why is such an inefficient strategy among colonies maintained by natural selection? Here, we show that inactive workers are necessary for the long-term sustainability of a colony. Our simulation shows that colonies with variable thresholds persist longer than those with invariable thresholds because inactive workers perform the critical function of replacing active workers when they become fatigued. Evidence of the replacement of active workers by inactive workers has been found in ant colonies. Thus, the presence of inactive workers increases the long-term persistence of the colony at the expense of decreasing short-term productivity. Inactive workers may represent a bet-hedging strategy in response to environmental stochasticity. PMID- 26880335 TI - Intersubunit Bridges of the Bacterial Ribosome. AB - The ribosome is a large two-subunit ribonucleoprotein machine that translates the genetic code in all cells, synthesizing proteins according to the sequence of the mRNA template. During translation, the primary substrates, transfer RNAs, pass through binding sites formed between the two subunits. Multiple interactions between the ribosomal subunits, termed intersubunit bridges, keep the ribosome intact and at the same time govern dynamics that facilitate the various steps of translation such as transfer RNA-mRNA movement. Here, we review the molecular nature of these intersubunit bridges, how they change conformation during translation, and their functional roles in the process. PMID- 26880340 TI - Corticostriatal plasticity modulation: New roads for therapeutic targets. PMID- 26880341 TI - The novel adaptive rotating beam test unmasks sensorimotor impairments in a transgenic mouse model of Parkinson's disease. AB - Development of disease modifying therapeutics for Parkinson's disease (PD), the second most common neurodegenerative disorder, relies on availability of animal models which recapitulate the disease hallmarks. Only few transgenic mouse models, which mimic overexpression of alpha-synuclein, show dopamine loss, behavioral impairments and protein aggregation. Mice overexpressing human wildtype alpha-synuclein under the Thy-1 promotor (Thy1-aSyn) replicate these features. However, female mice do not exhibit a phenotype. This was attributed to a potentially lower transgene expression located on the X chromosome. Here we support that female mice overexpress human wildtype alpha-synuclein only about 1.5 fold in the substantia nigra, compared to about 3 fold in male mice. Since female Thy1-aSyn mice were shown previously to exhibit differences in corticostriatal communication and synaptic plasticity similar to their male counterparts we hypothesized that female mice use compensatory mechanisms and strategies to not show overt motor deficits despite an underlying endophenotype. In order to unmask these deficits we translated recent findings in PD patients that sensory abnormalities can enhance motor dysfunction into a novel behavioral test, the adaptive rotating beam test. We found that under changing sensory input female Thy1-aSyn mice showed an overt phenotype. Our data supports that the integration of sensorimotor information is likely a major contributor to symptoms of movement disorders and that even low levels of overexpression of human wildtype alpha-synuclein has the potential to disrupt processing of these information. The here described adaptive rotating beam test represents a sensitive behavioral test to detect moderate sensorimotor alterations in mouse models. PMID- 26880342 TI - Inhibition of catecholamine degradation ameliorates while chemical sympathectomy aggravates the severity of acute Friend retrovirus infection in mice. AB - Several lines of evidence indicate that the sympathetic nervous system (SNS) might be involved in the pathogenesis and progression of retroviral infections. However, experimental data are scarce and findings inconsistent. Here, we investigated the role of the SNS during acute infection with Friend virus (FV), a pathogenic murine retrovirus that causes polyclonal proliferation of erythroid precursor cells and splenomegaly in adult mice. Experimental animals were infected with FV complex, and viral load, spleen weight, and splenic noradrenaline (NA) concentration was analyzed until 25 days post infection. Results show that FV infection caused a massive but transient depletion in splenic NA during the acute phase of the disease. At the peak of the virus induced splenomegaly, splenic NA concentration was reduced by about 90% compared to naive uninfected mice. Concurrently, expression of the catecholamine degrading enzymes monoamine oxidase A (MAO-A) and catechol-O-methyltransferase (COMT) was significantly upregulated in immune cells of the spleen. Pharmacological inhibition of MAO-A and COMT by the selective inhibitors clorgyline and 3,5 dinitrocatechol, respectively, efficiently blocked NA degradation and significantly reduced viral load and virus-induced splenomegaly. In contrast, chemical sympathectomy prior to FV inoculation aggravated the acute infection and extended the duration of the disease. Together these findings demonstrate that catecholamine availability at the site of viral replication is an important factor affecting the course of retroviral infections. PMID- 26880343 TI - Excessive behaviors in clinical practice--A state of the art article. AB - This paper concerns difficulties with excessive food intake, sexual activities, romantic relationships, gambling, Internet use, shopping, and exercise-behaviors that might cause considerable suffering. Excessive behaviors are seen as expressions of underlying difficulties that often co-occur with other psychological difficulties, and behaviors may accompany or replace each other. Moreover, they might pass unnoticed in clinical practice. Given the complexity of excessive behaviors, integrated and individualized treatment has been recommended. This paper presents an overview of the terminology concerning excessive behaviors, and the impact of naming is acknowledged. Thereafter, methods for identification and assessment, as well as treatment needs are discussed. Because identification, assessment, and treatment occur in an interaction between client and practitioner, this paper presents a discussion of the need to empower practitioners to identify and assess excessive behaviors and provide an integrated treatment. Moreover, the need to support practitioners' capacity to handle and tolerate the overwhelming suffering and the negative consequences connected to excessive behaviors is discussed. Qualitative studies are suggested in order to understand the meaning of excessive behaviors, treatment needs, and the interaction between client and practitioner. PMID- 26880344 TI - Reversible morphological changes of assembled supramolecular amphiphiles triggered by pH-modulated host-guest interactions. AB - Reversible template-directed micellar-size and shape modulation by virtue of host guest reversible docking of molecular templates at the micellar-solvent interface was achieved in water. By combining a pi-electron deficient bipyridinium-based gemini amphiphile which is capable of binding and aligning with a pi-electron rich tri(ethylene glycol)-disubstituted 1,5-diaminonaphthalene, a switchable detergent system which operates through the pH-responsive formation of bisammonium dications was realised. The binding of the 1,5-diaminonaphthalene guest to the bipyridinium-based micellar aggregate superstructure can be actuated by the addition of acid and base. Upon the addition of acid, protonation of the guest forming the dication deactivates molecular recognition with the charged head groups of the micellar aggregate by Coulombic repulsion. This process is completely reversible upon the addition of base, whereby the guest reintercalates into the superstructure -again forming donor-acceptor pi-pi stacks at the micellar-solvent interface amongst contiguous surfactant head groups. Synchrotron small angle X-ray scattering and dynamic laser light scattering confirm that this form of reversible directionally-templated micellisation results in an oblate spheroid-to-lamellar micelle morphological transition with a stabilising net decrease in the free energy of micellisation of 1.4 kcal mol(-1) per hydrophobic tail. PMID- 26880345 TI - 'Inflammatory myofibroblastic tumour'-like dedifferentiation of anaplastic lymphoma kinase-rearranged lung adenocarcinoma. AB - AIMS: Anaplastic lymphoma kinase (ALK) functions as an oncogenic driver in a subset of haematopoietic, epithelial and mesenchymal neoplasms. Activation of ALK most commonly occurs through gene fusion events, the presence of which predicts response to ALK-targeted inhibitors in some tumour types. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions represent the majority of ALK rearrangements in lung adenocarcinomas and were, until recently, thought to be exclusive to that tumour type. However, recent work has identified EML4-ALK fusions in ~20% of inflammatory myofibroblastic tumours (IMTs), particularly in those arising in the lung. Here, we present a patient with an ALK-rearranged poorly differentiated lung adenocarcinoma with a predominant sarcomatoid component that was morphologically indistinguishable from IMT. METHODS AND RESULTS: Targeted next-generation sequencing revealed EML4-ALK rearrangements in both components, with identical fusion sequences. Copy number analysis demonstrated focal gain of the MYC gene in the IMT-like component. The findings support a diagnosis of ALK-rearranged lung adenocarcinoma with IMT-like dedifferentiation. CONCLUSIONS: Our findings suggest that ALK-driven epithelial and mesenchymal neoplasms exist on a morphological spectrum, and emphasize the need to consider translocation testing in pulmonary tumours with unusual sarcomatoid morphology. PMID- 26880347 TI - Are We Emerging From the Ice Age of Liver Preservation? PMID- 26880346 TI - Apolipoprotein E allele frequencies in chronic and self-limited hepatitis C suggest a protective effect of APOE4 in the course of hepatitis C virus infection. AB - BACKGROUND & AIMS: Infectious hepatitis C virus (HCV) particles bind to host lipoproteins such as low-density lipoproteins (LDLs). Low-density lipoprotein receptors (LDLR) have been termed candidate receptors for HCV-LDL complexes. Functional host genetic single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene encoding apolipoprotein E (apoE) - a major structural LDL component and natural ligand of LDLR - likely influence the course of HCV infection. We investigated the prevalence of APOE SNPs in two large and independent cohorts of patients with chronic HCV infection compared to respective controls. METHODS: We genotyped 996 chronically HCV-infected patients; 179 patients with spontaneous HCV clearance; 283 individuals with non-HCV-associated liver disease; and 2 234 healthy controls. RESULTS: APOE genotype proportions in patients with persistent HCV infection significantly differed from healthy controls (P = 0.007) primarily because of a substantial under-representation of APOE4 alleles in chronically HCV-infected patients (10.2%) compared to 13.0% in healthy controls (P = 0.001). The distribution of APOE4 allele positive genotypes (epsilon2epsilon4, epsilon3epsilon4, epsilon4epsilon4) also significantly differed between chronically HCV-infected patients and healthy controls (1.4%, 17%, 1% vs. 2.4%, 20.5%, 1.7%; P = 0.001), suggesting a protective effect of the APOE4 allele in HCV infection. This was confirmed by a significant over representation of the APOE4 allele in patients with spontaneous HCV clearance (17.6%; P = 0.00008). The APOE4 allele distribution in patients with non-HCV associated liver disease (14.0%) was very similar to healthy controls and also differed from chronically HCV-infected patients (P = 0.012), suggesting HCV specificity. CONCLUSIONS: Our findings suggest that the APOE4 allele may confer a protective effect in the course of HCV infection. PMID- 26880348 TI - Perceptual biases in the horizontal and vertical dimensions are driven by separate cognitive mechanisms. AB - Perceptual attention in healthy participants is characterized by two biases, one operating in the horizontal plane, which draws attention leftward, and the other operating in the vertical plane, which draws attention upward. Given that these biases are reliably found in the same individual, and appear similar at a surface level, a number of researchers have investigated the relationship between horizontal and vertical attentional biases. To date, these investigations have failed to find an association, and this may be due to the fact that one dimensional vertical and horizontal stimuli were presented separately rather than being measured from a single, two-dimensional stimulus. Across three experiments, two dimensional stimuli were presented, and participants marked the centre of the stimuli. In addition, the shapes of the stimuli were manipulated to determine whether this produced the same modulation of the two biases. Across 13 stimuli and three experiments there were no correlations between the vertical and horizontal biases. In addition, manipulations of stimulus shape, which affected biases in one dimension, did not affect biases in the other dimension. There were, however, consistent correlations between the degree of bias within each dimension across the different stimuli. This study has produced converging evidence that horizontal and vertical biases in spatial judgments rely on separate cognitive mechanisms. To account for these results we discuss a model whereby horizontal asymmetries rely more on space-based mechanisms whereas vertical asymmetries rely more on object-based mechanisms. PMID- 26880349 TI - Stability of B12 (CN)12 (2-) : Implications for Lithium and Magnesium Ion Batteries. AB - Multiply charged negative ions are seldom stable in the gas phase. Electrostatic repulsion leads either to autodetachment of electrons or fragmentation of the parent ion. With a binding energy of the second electron at 0.9 eV, B12 H12 (2-) is a classic example of a stable dianion. It is shown here that ligand substitution can lead to unusually stable multiply charged anions. For example, dodecacyanododecaborate, B12 (CN)12 (2-) , created by substituting H by CN is found to be highly stable with the second electron bound by 5.3 eV, which is six times larger than that in the B12 H12 (2-) . Equally important is the observation that CB11 (CN)12 (2-) , which contains one electron more than needed to satisfy the Wade-Mingos rule, is also stable with its second electron bound by 1.1 eV, while CB11 H12 (2-) is unstable. The ability to stabilize multiply charged anions in the gas phase by ligand manipulation opens a new door for multiply charged species with potential applications as halogen-free electrolytes in ion batteries. PMID- 26880350 TI - Bis-tert-Alcohol-Functionalized Crown-6-Calix[4]arene: An Organic Promoter for Nucleophilic Fluorination. AB - A bis-tert-alcohol-functionalized crown-6-calix[4]arene (BACCA) was designed and prepared as a multifunctional organic promoter for nucleophilic fluorinations with CsF. By formation of a CsF/BACCA complex, BACCA could release a significantly active and selective fluoride source for SN2 fluorination reactions. The origin of the promoting effects of BACCA was studied by quantum chemical methods. The role of BACCA was revealed to be separation of the metal fluoride to a large distance (>8 A), thereby producing an essentially "free" F( ). The synergistic actions of the crown-6-calix[4]arene subunit (whose O atoms coordinate the counter-cation Cs(+)) and the terminal tert-alcohol OH groups (forming controlled hydrogen bonds with F(-)) of BACCA led to tremendous efficiency in SN2 fluorination of base-sensitive substrates. PMID- 26880351 TI - Editorial: The Rhoton Collection and the Journal of Neurosurgery: expanding the reach of neuroanatomy in the digital print world. PMID- 26880352 TI - Lipoprotein(a) and Increased Cardiovascular Risk in Women. AB - BACKGROUND: Approximately 20% of the population has elevated circulating levels of lipoprotein(a) (Lp[a]), one of the most robust predictors of cardiovascular disease risk. This is particularly true for women. HYPOTHESIS: Many female patients with "normal" traditional risk factors or low atherosclerotic cardiovascular disease (ASCVD) risk scores may harbor high risk related to elevated levels of Lp(a). METHODS: A retrospective, cross-sectional study of consecutive female patients presenting to Heart Centers for Women was performed. Discordance between low-density lipoprotein cholesterol (LDL-C) and Lp(a) was determined. The ASCVD risk and Reynolds Risk Score models A (RRS-A) and B (RRS-B) were calculated, and level of agreement in patients meeting treatment threshold (>=7.5% for ASCVD, >=10% for RRS-A and RRS-B) were compared. RESULTS: Among 713 women, 290 (41%) had elevated Lp(a); however, LDL-C and Lp(a) were weakly correlated (r = 0.08). Significant discordance was observed between abnormal LDL C and Lp(a) levels (McNemar P = 0.03). There was moderate correlation between RRS A and ASCVD risk (r = 0.71, P < 0.001), and Bland-Altman plot showed diminished correlation with increased risk. More patients met treatment threshold by ASCVD risk estimation, but nearly 1 out of 20 patients met treatment threshold by RRS-A but not ASCVD score. CONCLUSIONS: There is high prevalence of elevated Lp(a) among women presenting to Heart Centers for Women. Although traditional risk markers such as elevated LDL-C or high ASCVD risk may be absent in some women, elevated Lp(a) may identify patients who may benefit from aggressive risk-factor modification and pharmacologic therapy. PMID- 26880353 TI - Ancient and modern colonization of North America by hemlock woolly adelgid, Adelges tsugae (Hemiptera: Adelgidae), an invasive insect from East Asia. AB - Hemlock woolly adelgid, Adelges tsugae, is an invasive pest of hemlock trees (Tsuga) in eastern North America. We used 14 microsatellites and mitochondrial COI sequences to assess its worldwide genetic structure and reconstruct its colonization history. The resulting information about its life cycle, biogeography and host specialization could help predict invasion by insect herbivores. We identified eight endemic lineages of hemlock adelgids in central China, western China, Ulleung Island (South Korea), western North America, and two each in Taiwan and Japan, with the Japanese lineages specializing on different Tsuga species. Adelgid life cycles varied at local and continental scales with different sexual, obligately asexual and facultatively asexual lineages. Adelgids in western North America exhibited very high microsatellite heterozygosity, which suggests ancient asexuality. The earliest lineages diverged in Asia during Pleistocene glacial periods, as estimated using approximate Bayesian computation. Colonization of western North America was estimated to have occurred prior to the last glacial period by adelgids directly ancestral to those in southern Japan, perhaps carried by birds. The modern invasion from southern Japan to eastern North America caused an extreme genetic bottleneck with just two closely related clones detected throughout the introduced range. Both colonization events to North America involved host shifts to unrelated hemlock species. These results suggest that genetic diversity, host specialization and host phylogeny are not predictive of adelgid invasion. Monitoring non-native sentinel host trees and focusing on invasion pathways might be more effective methods of preventing invasion than making predictions using species traits or evolutionary history. PMID- 26880354 TI - Making microbiology of the built environment relevant to design. AB - Architects are enthusiastic about "bioinformed design" as occupant well-being is a primary measure of architectural success. However, architects are also under mounting pressure to create more sustainable buildings. Scientists have a critical opportunity to make the emerging field of microbiology of the built environment more relevant and applicable to real-world design problems by addressing health and sustainability in tandem. Practice-based research, which complements evidence-based design, represents a promising approach to advancing knowledge of the indoor microbiome and translating it to architectural practice. PMID- 26880355 TI - Dye-Sensitized Cu2 XSnS4 (X=Zn, Ni, Fe, Co, and Mn) Nanofibers for Efficient Photocatalytic Hydrogen Evolution. AB - The photocatalytic hydrogen evolution activities of low-cost and noble-metal-free Cu2 XSnS4 (X=Zn, Ni, Fe, Co, and Mn) nanofiber catalysts have been investigated using triethanolamine as an electron donor and eosin Y as a photosensitizer under visible-light irradiation. The rates of hydrogen evolution by Cu2 XSnS4 (X=Zn, Ni, Fe, Co, and Mn) nanofibers have been compared with each other and with that of the noble metal Pt. The hydrogen evolution rates for the nanofibers change in the order Cu2 NiSnS4 >Cu2 FeSnS4 >Cu2 CoSnS4 >Cu2 ZnSnS4 >Cu2 MnSnS4 (2028, 1870, 1926, 1420, and 389 MUmol g(-1) h(-1) , respectively). The differences between the hydrogen evolution rates of the nanofibers could be attributed to their energy levels. Moreover, Cu2 NiSnS4, Cu2 FeSnS4 , and Cu2 CoSnS4 nanofibers show higher and more stable photocatalytic hydrogen production rates than that of the noble metal Pt under long-term irradiation with visible light. PMID- 26880356 TI - Contraception: the Need for Expansion of Counsel in Adolescent and Young Adult (AYA) Cancer Care. AB - Little is known about oncology provider recommendations regarding best practices in contraception use during cancer treatment and through survivorship for adolescent and young adult (AYA) cancer patients. This review examined the literature to identify related studies on contraception recommendations, counseling discussions, and methods of contraception in the AYA oncology population. A literature review was conducted using PubMed, including all peer reviewed journals with no publication date exclusions. A systematic review of the literature was conducted using combinations of the following phrases or keywords: "oncology OR cancer" AND "contraception, family planning, contraceptive devices, contraceptive agents, intrauterine devices OR IUD, vaccines, spermatocidal agents, postcoital, immunologic, family planning, vasectomy, tubal ligation, sterilization" AND "young adult OR adolescent" AND "young adult AND adolescent". Reviewers assessed articles using the "Quality Assessment Tool for Quantitative Studies" which considers: (1) selection bias; (2) study design; (3) confounders; (4) blinding; (5) data collection methods; and (6) withdrawals and dropouts. A total of five articles were included and all studies were quantitative. Results showed no consistent recommendations among providers, references to guidelines, or methods of contraceptive types. Provider guidelines for discussions with AYA patients should be expanded to provide comprehensive, consistent, and quality cancer care in the AYA population. PMID- 26880359 TI - Tourism-Induced Livelihood Changes at Mount Sanqingshan World Heritage Site, China. AB - Although tourism has the potential to improve the wellbeing of residents, it may also disrupt livelihood systems, social processes, and cultural traditions. The livelihood changes at three rural villages at Mount Sanqingshan World Heritage Site, China, are assessed to determine the extent to which tourism strategies are contributing to local livelihoods. A sustainable livelihood framework is adopted to guide the analysis. The three villages exhibit different development patterns due to institutional, organizational, and location factors. New strategies involving tourism were constructed and incorporated into the traditional livelihood systems and they resulted in different outcomes for residents of different villages. Village location, including the relationship to the site tourism plan, affected the implications for rural livelihoods. High dependence on tourism as the single livelihood option can reduce sustainability. Practical implications are suggested to enhance livelihood sustainability at such rural heritage tourism sites. PMID- 26880358 TI - Individual Variations in Nucleus Accumbens Responses Associated with Major Depressive Disorder Symptoms. AB - Abnormal reward-related responses in the nucleus accumbens (NAcc) have been reported for major depressive disorder (MDD) patients. However, variability exists in the reported results, which could be due to heterogeneity in neuropathology of depression. To parse the heterogeneity of MDD we investigated variation of NAcc responses to gain and loss anticipations using fMRI. We found NAcc responses to monetary gain and loss were significantly variable across subjects in both MDD and healthy control (HC) groups. The variations were seen as a hyperactive response subtype that showed elevated activation to the anticipation of both gain and loss, an intermediate response with greater activation to gain than loss, and a suppressed-activity with reduced activation to both gain and loss compared to a non-monetary condition. While these response variability were seen in both MDD and HC subjects, specific symptoms were significantly associated with the right NAcc variation in MDD. Both the hyper- and suppressed-activity subtypes of MDD patients had severe suicidal ideation and anhedonia symptoms. The intermediate subjects had less severity in these symptoms. These results suggest that differing propensities in reward responsiveness in the NAcc may affect the development of specific symptoms in MDD. PMID- 26880357 TI - Knowledge and Attitudes Towards Human Papillomavirus (HPV) Among Academic and Community Physicians in Mangalore, India. AB - Cervical cancer is the most common cancer found in Indian women. Two human papillomavirus (HPV) vaccines were approved for use in India in 2006; however, neither has become readily accepted. Physician attitudes and recommendations are crucial in the uptake of HPV vaccines among adolescent women in the USA; thus, we ought to investigate provider attitudes and practices related to HPV vaccination in India via a survey administered to 210 Indian physicians. Of the 210 physicians, 46 % were community physicians and 54 % were academic physicians. The correct response to HPV knowledge questions was identified around 50 % of the time in 6/11 questions. Only 47 % of the physicians knew that there was an HPV vaccine approved for use in India. Only 11 % and 15 % of physicians strongly agree that the HPV vaccine will lead to long-lasting immunity and has a safe side effect profile, respectively. A total of 30 % of those surveyed reported that they would recommend the HPV vaccine to their patients, while 73 % agreed that the cost of the HPV vaccine is a major barrier to acceptance. After multivariate analysis, there were two significant variables independently associated with a physician's decision to recommend HPV vaccine. These variables were as follows: "whether the vaccine was freely available from the government sector" and "uncertainty about whether HPV must be persistent to cause cervical cancer vs not." Given the lack of knowledge among practicing physicians in Mangalore, increasing the education about HPV infection and HPV vaccination towards health care providers has the potential to increase vaccine recommendations. PMID- 26880360 TI - Apical lymph node dissection of the inferior mesenteric artery. AB - AIM: It is controversial whether a high or low ligation of the inferior mesenteric artery (IMA) is superior. The former allows an extended lymph node clearance whereas the latter preserves the distal vascular supply via the left colic artery (LCA). Apical lymph node dissection of the IMA (ALMA) harvests nodal tissue along the IMA proximal to the LCA whilst performing a low ligation. This anatomically replicates the oncological benefit of high ligation and the vascular preservation of low ligation. Our study evaluates the nodal yield of ALMA and the short-term outcome of this technique. METHOD: We retrospectively studied 19 patients with sigmoid or rectal cancer who underwent curative surgical resection with ALMA. All ALMAs were performed with a standard technique previously described (Kobayashi et al., Surg Endosc 2005, 20:563-9; Sekimoto et al. Surg Endosc 2010, 25:861-6) . The lymph node yield from the dissection (the ALMA specimen) was compared with the total lymph node yield. Data on the LCA anatomy, time required to perform ALMA, complications and postoperative recovery were evaluated. RESULTS: ALMA was successful in 18 patients. Median postoperative hospitalization was 5 (2-26) days without ALMA-related morbidity or mortality. The median lymph node yield was 20 (9-41) and a median of 14.3 (0-80)% were harvested with ALMA. Two patients not having neoadjuvant chemoradiotherapy had fewer than 12 lymph nodes, excluding nodes harvested from ALMA. The average time required for ALMA was 18 min. CONCLUSION: ALMA is a safe and feasible technique, allowing extended lymphadenectomy without sacrificing the LCA. In this small group of patients none were upstaged due to cancerous involvement of the proximal nodes. PMID- 26880361 TI - The importance of mold sensitivity in nonallergic rhinitis patients. AB - BACKGROUND: In recent studies, local specific immunoglobulin E (sIgE) production against allergens in nasal mucosa and a positive response to a nasal allergen provocation test (NAPT) have been demonstrated in some patients initially diagnosed as nonallergic rhinitis (NAR) or idiopathic rhinitis (IR). The aim of this study was to evaluate the presence of local allergic rhinitis (LAR) in patients who experience rhinitis symptoms in indoor and outdoor moldy conditions and to investigate the role of the NAPT in diagnosis. METHODS: A total of 40 NAR patients with a history of persistent rhinitis and who had negative skin-prick tests (SPTs) and serum sIgE levels to common aeroallergens, as well as 20 healthy subjects were included in the study. NAPTs were performed with Aspergillus fumigatus (group 1) or a mixture of Alternaria alternata and Cladosporium herbarum extracts (group 2). RESULTS: In patient nasal lavage fluids, tryptase and mold sIgE levels were not significantly different from the control group. NAPT with Aspergillus fumigatus was positive in 8 of 12 NAR patients (66.6%) in group 1 and NAPT with the mixture of extracts was positive in 9 of 13 NAR patients (69.2%) in group 2. CONCLUSION: This study suggests that LAR may exist in a significant number of the persistent rhinitis patients who were previously considered as NAR based on negative SPTs or serum sIgE tests. To the best of our knowledge, this is the first study evaluating a nasal local allergic response to both indoor and outdoor molds. PMID- 26880362 TI - Estimating Infection Incidence in Longitudinal Studies. PMID- 26880363 TI - Daldionin, an Unprecedented Binaphthyl Derivative, and Diverse Polyketide Congeners from a Fungal Orchid Endophyte. AB - Thailand possesses a rich diversity of orchid species that, in turn, live in symbiosis with a wide variety of fungi. Such endophytes have the potential to produce secondary metabolites with bioactivity against orchid and/or human pathogens. The orchid-associated fungal strain Daldinia eschscholtzii was found to produce a diverse range of aromatic polyketides including the new naphthalene derivatives daldionin, nodulones B and C, and daldinones F and G along with eight known compounds. Daldionin possesses an unprecedented oxane-linked binaphthyl ring system. These compounds demonstrate the high diversity of structural variations that are constructed during fungal biosynthesis, and the results include important observations concerning the biosynthesis of binaphthyl derivatives. Daldionin was found to have weak antiproliferative activity against HUVEC and K-562 cell lines. All but one of the isolated compounds showed moderate antimicrobial activity towards at least one of the four tested microbial strains. PMID- 26880365 TI - Non-electrolytic synthesis of copper oxide/carbon nanocomposite by surface plasma in super-dehydrated ethanol. AB - Electrolytic processes are widely used to synthesize different nanomaterials and it does not depend on what kind of the method has been applied (wet-chemistry, sonochemistry, plasma chemistry, electrolysis and so on). Generally, the reactions in the electrolyte are considered to be reduction/oxidation (REDOX) reactions between chemical reagents or the deposition of matter on the electrodes, in line with Faraday's law. Due to the presence of electroconductive additives in any electrolyte, the polarization effect of polar molecules conducting an electrical current disappears, when external high-strength electric field is induced. Because initially of the charge transfer always belongs of electroconductive additive and it does not depend on applied voltage. The polarization of ethanol molecules has been applied to conduct an electric current by surface plasma interaction for the synthesis of a copper oxide/carbon nanocomposite material. PMID- 26880364 TI - Seasonal changes in the expression of energy metabolism-related genes in white adipose tissue and skeletal muscle in female Japanese black bears. AB - Bears undergo annual cycles in body mass: rapid fattening in autumn (i.e., hyperphagia), and mass loss in winter (i.e., hibernation). To investigate how Japanese black bears (Ursus thibetanus japonicus) adapt to such extreme physiological conditions, we analyzed changes in the mRNA expression of energy metabolism-related genes in white adipose tissues and skeletal muscle throughout three physiological stages: normal activity (June), hyperphagia (November), and hibernation (March). During hyperphagia, quantitative real-time polymerase chain reaction analysis revealed the upregulation of de novo lipogenesis-related genes (e.g., fatty acid synthase and diacylglycerol O-acyltransferase 2) in white adipose tissue, although the bears had been maintained with a constant amount of food. In contrast, during the hibernation period, we observed a downregulation of genes involved in glycolysis (e.g., glucose transporter 4) and lipogenesis (e.g., acetyl-CoA carboxylase 1) and an upregulation of genes in fatty acid catabolism (e.g., carnitine palmitoyltransferase 1A) in both tissue types. In white adipose tissues, we observed upregulation of genes involved in glyceroneogenesis, including pyruvate carboxylase and phosphoenolpyruvate carboxykinase 1, suggesting that white adipose tissue plays a role in the recycling of circulating free fatty acids via re-esterification. In addition, the downregulation of genes involved in amino acid catabolism (e.g., alanine aminotransferase) and the TCA cycle (e.g., pyruvate carboxylase) indicated a role of skeletal muscle in muscle protein sparing and pyruvate recycling via the Cori cycle. These examples of coordinated transcriptional regulation would contribute to rapid mass gain during the pre-hibernation period and to energy preservation and efficient energy production during the hibernation period. PMID- 26880366 TI - Landmark estimation of survival and treatment effects in observational studies. AB - Clinical studies aimed at identifying effective treatments to reduce the risk of disease or death often require long term follow-up of participants in order to observe a sufficient number of events to precisely estimate the treatment effect. In such studies, observing the outcome of interest during follow-up may be difficult and high rates of censoring may be observed which often leads to reduced power when applying straightforward statistical methods developed for time-to-event data. Alternative methods have been proposed to take advantage of auxiliary information that may potentially improve efficiency when estimating marginal survival and improve power when testing for a treatment effect. Recently, Parast et al. (J Am Stat Assoc 109(505):384-394, 2014) proposed a landmark estimation procedure for the estimation of survival and treatment effects in a randomized clinical trial setting and demonstrated that significant gains in efficiency and power could be obtained by incorporating intermediate event information as well as baseline covariates. However, the procedure requires the assumption that the potential outcomes for each individual under treatment and control are independent of treatment group assignment which is unlikely to hold in an observational study setting. In this paper we develop the landmark estimation procedure for use in an observational setting. In particular, we incorporate inverse probability of treatment weights (IPTW) in the landmark estimation procedure to account for selection bias on observed baseline (pretreatment) covariates. We demonstrate that consistent estimates of survival and treatment effects can be obtained by using IPTW and that there is improved efficiency by using auxiliary intermediate event and baseline information. We compare our proposed estimates to those obtained using the Kaplan-Meier estimator, the original landmark estimation procedure, and the IPTW Kaplan-Meier estimator. We illustrate our resulting reduction in bias and gains in efficiency through a simulation study and apply our procedure to an AIDS dataset to examine the effect of previous antiretroviral therapy on survival. PMID- 26880368 TI - Determination of the Absolute Configuration of the Pseudo-Symmetric Natural Product Elatenyne by the Crystalline Sponge Method. AB - Elatenyne is a marine natural product that was isolated in 1986. Despite its simple 2,2'-bifuranyl backbone, its relative structure was only recently determined. The absolute configuration of elatenyne has still not been unequivocally confirmed because of its pseudo-meso core structure, which results in a specific rotation, [alpha]D , of almost zero. In this work, the structure of natural elatenyne was determined by the crystalline sponge method and the use of a porous coordination network (a crystalline sponge) capable of absorbing organic guests; in the sponge, the absorbed guests are ordered and crystallographically observable. The crystalline sponge could differentiate between the two very similar alkyl side chains, and the absolute structure of elatenyne was thus reliably determined. The total amount required for the experiments was only approximately 100 MUg, and the majority (95 MUg) could be recovered after the experiments. PMID- 26880369 TI - Australian doctors refuse to discharge refugee girl into government detention. PMID- 26880370 TI - Mutation of epigenetic regulators TET2 and MLL3 in patients with HTLV-I-induced acute adult T-cell leukemia. AB - BACKGROUND: Epigenetic regulators play a critical role in the maintenance of specific chromatin domains in an active or repressed state. Disruption of epigenetic regulatory mechanisms is widespread in cancer cells and largely contributes to the transformation process through active repression of tumor suppressor genes. While mutations of epigenetic regulators have been reported in various lymphoid malignancies and solid cancers, mutation of these genes in HTLV I-associated T-cell leukemia has not been investigated. METHOD: Here we used whole genome next generation sequencing (NGS) of uncultured freshly isolated ATL samples and identified the presence of mutations in SUZ12, DNMT1, DNMT3A, DNMT3B, TET1, TET2, IDH1, IDH2, MLL, MLL2, MLL3 and MLL4. RESULTS: TET2 was the most frequently mutated gene, occurring in 32 % (10/31) of ATL samples analyzed. Interestingly, NGS revealed nonsense mutations accompanied by loss of heterozygosity (LOH) in TET2 and MLL3, which was further confirmed by cloning and direct sequencing of DNA from uncultured cells. Finally, direct sequencing of matched control and tumor samples revealed that TET2 mutation was present only in ATL tumor cells. CONCLUSIONS: Our results suggest that inactivation of MLL3 and TET2 may play an important role in the tumorigenesis process of HTLV-I-induced ATL. PMID- 26880371 TI - The neutrophil-to-lymphocyte ratio in patients with obstructive sleep apnoea syndrome and its relationship with cardiovascular disease. AB - OBJECTIVE: To investigate the association between the neutrophil-to-lymphocyte ratio (NLR) and obstructive sleep apnoea syndrome (OSAS) severity and whether the NLR predicts cardiovascular disease (CVD) in patients with OSAS. BACKGROUND: OSAS is known as a risk factor for CVD. An increased NLR was strongly correlated with cardiovascular outcomes in several studies. METHODS: We retrospectively examined the laboratory data for 289 patients with suspected OSAS evaluated using polysomnography. RESULTS: The study included 171 OSAS patients and 118 controls. The NLR was higher in OSAS group than control group. The NLR was significantly higher in patients with CVD than in those without (3.31 +/- 1.1 vs. 1.93 +/- 0.8, p = 0.002). There were also significant correlations between the NLR and apnoea hypopnoea index, mean SaO2, and oxygen desaturation index. CONCLUSIONS: There was a significant correlation between the NLR and OSAS severity and the NLR was independently associated with CVD in patients with OSAS. PMID- 26880372 TI - Continuous-Flow N-Heterocyclic Carbene Generation and Organocatalysis. AB - Two methods were assessed for the generation of common N-heterocyclic carbenes (NHCs) from stable imidazol(in)ium precursors using convenient and straightforward continuous-flow setups with either a heterogeneous inorganic base (Cs2CO3 or K3PO4) or a homogeneous organic base (KN(SiMe3)2). In-line quenching with carbon disulfide revealed that the homogeneous strategy was most efficient for the preparation of a small library of NHCs. The generation of free nucleophilic carbenes was next telescoped with two benchmark NHC-catalyzed reactions; namely, the transesterification of vinyl acetate with benzyl alcohol and the amidation of N-Boc-glycine methyl ester with ethanolamine. Both organocatalytic transformations proceeded with total conversion and excellent yields were achieved after extraction, showcasing the first examples of continuous-flow organocatalysis with NHCs. PMID- 26880375 TI - Pain in children and adolescents with cerebral palsy: a population-based registry study. AB - AIM: We assessed prevalence and location of pain in a total population of children and adolescents with cerebral palsy (CP) based on the Gross Motor Function Classification System (GMFCS), age and gender. METHODS: This cross sectional study was based on the last assessment of children aged 1-14 years in the combined Swedish follow-up programme and national quality register programme for CP. All were born 2001-2012 and reported to the registry in 2013-2014. Logistic regression was used to regress age, gender and the GMFCS level on the presence of pain. We also assessed pain sites among GMFCS groups. RESULTS: We included 2777 children (57% boys) at a median age of 7 years; 32.4% reported pain, with significantly more girls than boys experiencing pain and significantly more children at GMFCS levels III and V than GMFCS I. Pain frequency increased with age and differences among GMFCS levels were found in the lower extremities and abdomen. Pain in the abdomen and hips was most frequent at GMFCS V, knee pain at level III and foot pain at level I. CONCLUSION: Our results showed that although a lower prevalence than in many other studies, pain constituted a significant problem in children and adolescents with CP. PMID- 26880374 TI - Guidelines for the Management of Pregnant Women With Substance Use Disorders. AB - BACKGROUND: Women of reproductive potential with substance use disorders, especially those who are pregnant, present many clinical challenges to healthcare providers, including comorbid psychiatric disorders, a history of trauma and abuse, avoidance of or poor access to prenatal care, fear of legal consequences, and countertransference reactions. METHODS: In November 2013, members of the Women's Mental Health Special Interest Group of the Academy of Psychosomatic Medicine presented a Workshop reviewing substance abuse in pregnancy, highlighting the specific contributions that psychosomatic medicine specialists can make in the care of these patients. The discussion focused on epidemiology; maternal and fetal risks; and screening and treatment considerations for tobacco, alcohol, cannabis, opioids, benzodiazepines, stimulants, and several other substances. OBJECTIVE: Our purpose in publishing this review is to provide clinicians and educators with the most up-to-date summary in this field to better engage these patients in care and break the intergenerational cycle of abuse and addiction. PMID- 26880373 TI - Reduction of self-perceived discomforts in critically ill patients in French intensive care units: study protocol for a cluster-randomized controlled trial. AB - BACKGROUND: It is now well documented that critically ill patients are exposed to stressful conditions and experience discomforts from multiple sources. Improved identification of the discomforts of patients in intensive care units (ICUs) may have implications for managing their care, including consideration of ethical issues, and may assist clinicians in choosing the most appropriate interventions. The primary objective of this study was to assess the effectiveness of a multicomponent program of discomfort reduction in critically ill patients. The secondary objectives were to assess the sustainability of the impact of the program and the potential seasonality effect. METHODS/DESIGN: We conducted a multicenter, cluster-randomized, controlled, single (patient)-blind study involving 34 French adult ICUs. The experimental intervention was a 6-month period during which the multicomponent program was implemented in the ICU and included the following steps: identification of discomforts, immediate feedback to the healthcare team, and implementation of targeted interventions. The control intervention was a 6-month period during which any program was implemented. The primary endpoint was the monthly overall score of self-reported discomfort from the French questionnaire on discomforts in ICU patients (IPREA). The secondary endpoints were the scores of the discomfort items of IPREA. The sample size was 660 individuals to obtain 80% power to detect a 25% difference in the overall discomfort score of IPREA between the two groups (design effect: 2.9). DISCUSSION: The results of this cluster-randomized controlled study are expected to confirm that a multicomponent program of discomfort reduction may be a new strategy in the management of care for critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02442934, registered 11 May 2015. PMID- 26880376 TI - EPR Steering inequalities with Communication Assistance. AB - In this paper, we investigate the communication cost of reproducing Einstein Podolsky-Rosen (EPR) steering correlations arising from bipartite quantum systems. We characterize the set of bipartite quantum states which admits a local hidden state model augmented with c bits of classical communication from an untrusted party (Alice) to a trusted party (Bob). In case of one bit of information (c = 1), we show that this set has a nontrivial intersection with the sets admitting a local hidden state and a local hidden variables model for projective measurements. On the other hand, we find that an infinite amount of classical communication is required from an untrusted Alice to a trusted Bob to simulate the EPR steering correlations produced by a two-qubit maximally entangled state. It is conjectured that a state-of-the-art quantum experiment would be able to falsify two bits of communication this way. PMID- 26880377 TI - Molecular Basis for Differential Anion Binding and Proton Coupling in the Cl( )/H(+) Exchanger ClC-ec1. AB - Cl-/H+ transporters of the CLC superfamily form a ubiquitous class of membrane proteins that catalyze stoichiometrically coupled exchange of Cl- and H+ across biological membranes. CLC transporters exchange H+ for halides and certain polyatomic anions, but exclude cations, F-, and larger physiological anions, such as PO43- and SO42-. Despite comparable transport rates of different anions, the H+ coupling in CLC transporters varies significantly depending on the chemical nature of the transported anion. Although the molecular mechanism of exchange remains unknown, studies on bacterial ClC-ec1 transporter revealed that Cl- binding to the central anion-binding site (Scen) is crucial for the anion-coupled H+ transport. Here, we show that Cl-, F-, NO3-, and SCN- display distinct binding coordinations at the Scen site and are hydrated in different manners. Consistent with the observation of differential bindings, ClC-ec1 exhibits markedly variable ability to support the formation of the transient water wires, which are necessary to support the connection of the two H+ transfer sites (Gluin and Gluex), in the presence of different anions. While continuous water wires are frequently observed in the presence of physiologically transported Cl-, binding of F- or NO3- leads to the formation of pseudo-water-wires that are substantially different from the wires formed with Cl-. Binding of SCN-, however, eliminates the water wires altogether. These findings provide structural details of anion binding in ClC-ec1 and reveal a putative atomic-level mechanism for the decoupling of H+ transport to the transport of anions other than Cl-. PMID- 26880378 TI - The establishment of species-specific primers for the molecular identification of ten stored-product psocids based on ITS2 rDNA. AB - Psocids are important stored product pests found worldwide that can be spread through grain trade. Most stored-product psocids, including eggs, nymphs, and adults, are very small (~1 mm) and difficult to identify morphologically. Here, we collected 10 economically important stored-product Liposcelis spp. psocids (L. bostrychophila, L. entomophila, L. decolor, L. paeta, L. brunnea, L. corrodens, L. mendax, L. rufa, L. pearmani, and L. tricolor) from 35 geographical locations in 5 countries (China, Czech Republic, Denmark, Germany, and the United States). The ITS2 rDNA gene was extracted and sequenced. The interspecific genetic distance of the stored-product psocids was significantly higher than the intraspecific genetic distance according to the barcoding gap analysis. Ten pairs of species-specific primers based on the ITS2 rDNA were developed for psocid identification. The sensitivity estimation indicated that the species-specific primers could correctly amplify the target ITS2 gene and successfully identify psocids at 1.0 ng/mL. Additionally, these species-specific primers could quantify specificity and identify 10 stored-product psocids; this approach could also be used to accurately identify other stored-product psocids. This work provides a practical approach for the precise examination of 10 stored-product psocid species and also contributes to the development of an identification method using ITS2 rDNA. PMID- 26880379 TI - The potential of methylxanthine-based therapies in pediatric respiratory tract diseases. AB - Caffeine, theophylline and theobromine are the most known methylxanthines as they are present in coffee, tea and/or chocolate. In the last decades, a huge experimental effort has been devoted to get insight into the variety of actions that these compounds exert in humans. From such knowledge it is known that methylxanthines have a great potential in prevention, therapy and/or management of a variety of diseases. The benefits of methylxanthine-based therapies in the apnea of prematurity and their translational potential in pediatric affections of the respiratory tract are here presented. PMID- 26880380 TI - Development of Photoactivatable Allosteric Modulators for the Chemokine Receptor CXCR3. AB - The CXCR3 receptor, a class A G protein-coupled receptor (GPCR), is involved in the regulation and trafficking of various immune cells. CXCR3 antagonists have been proposed to be beneficial for the treatment of a wide range of disorders including but not limited to inflammatory and autoimmune diseases. The structure based design of CXCR3 ligands remains, however, hampered by a lack of structural information describing in detail the interactions between an allosteric ligand and the receptor. We designed and synthesized photoactivatable probes for the structural and functional characterization, using photoaffinity labeling followed by mass spectrometry, of the CXCR3 allosteric binding pocket of AMG 487 and RAMX3, two potent and selective CXCR3 negative allosteric modulators. Photoaffinity labeling is a common approach to elucidate binding modes of small molecule ligands of GPCRs through the aid of photoactivatable probes that convert to extremely reactive intermediates upon photolysis. The photolabile probe N-[({1 [3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}-2-[4 fluoro-3-(trifluoromethyl)phenyl]-N-{1-[4-(3-(trifluoromethyl)-3H-diazirin-3 yl]benzyl}piperidin-4-yl)methyl]acetamide (10) showed significant labeling of the CXCR3 receptor (80%) in a [(3) H]RAMX3 radioligand displacement assay. Compound 10 will serve as an important tool compound for the detailed investigation of the binding pocket of CXCR3 by mass spectrometry. PMID- 26880381 TI - Demonstration of Synaptic Behaviors and Resistive Switching Characterizations by Proton Exchange Reactions in Silicon Oxide. AB - We realize a device with biological synaptic behaviors by integrating silicon oxide (SiO(x)) resistive switching memory with Si diodes. Minimal synaptic power consumption due to sneak-path current is achieved and the capability for spike induced synaptic behaviors is demonstrated, representing critical milestones for the use of SiO2-based materials in future neuromorphic computing applications. Biological synaptic behaviors such as long-term potentiation (LTP), long-term depression (LTD) and spike-timing dependent plasticity (STDP) are demonstrated systematically using a comprehensive analysis of spike-induced waveforms, and represent interesting potential applications for SiO(x)-based resistive switching materials. The resistive switching SET transition is modeled as hydrogen (proton) release from (SiH)2 to generate the hydrogen bridge defect, and the RESET transition is modeled as an electrochemical reaction (proton capture) that re forms (SiH)2. The experimental results suggest a simple, robust approach to realize programmable neuromorphic chips compatible with large-scale CMOS manufacturing technology. PMID- 26880382 TI - The PD-1/PD-L1 axis in the pathogenesis of urothelial bladder cancer and evaluating its potential as a therapeutic target. PMID- 26880383 TI - Novel therapies for advanced squamous cell carcinoma of the lung. AB - Advanced squamous non-small-cell lung carcinoma (SqCC) has traditionally been considered the 'neglected sibling' compared with lung adenocarcinoma due to lack of effective targeted treatment options. Currently, limited progress has been made in the systemic treatment of advanced disease and combination chemotherapy remains the gold standard. However, the recent completion of the molecular characterization of SqCC revealed an interestingly complex genomic profile, comprising various genetic alterations that can potentially function as molecular targets for the development of novel targeted agents. Recent encouraging results of the use of immune checkpoint inhibitors in several neoplasms has emerged as a promising novel treatment option for advanced SqCC. Future personalized studies, enrolling SqCC patients according to specific driving mutations are underway. PMID- 26880385 TI - Cancer as a changed tissue's way of life (when to treat, when to watch and when to think). AB - The profound scientific and commercial success of molecular biology, the progress of 'cancer gene' investigation technologies, together, pushed forward the postulate that genes explain 'everything'. Yet, during the last few years the microenvironments of solid tumors have emerged as key modulators of initiation, progression and metastasis and as essential to the therapeutic response. In the present review, we provide a synthetic examination of the main traits of cells embedded into the cancer stroma and emphasize several evidences that all components of the tumor tissue cooperate in space and time. Then we turn to discuss the epitheliocentric somatic mutational view and other new paradigms assuming that disturbed tissue interactions among cell populations are critical to cancer causation, growth and spread. PMID- 26880386 TI - Highlights of the San Antonio Breast Cancer Symposium 2015: part 2. AB - 38th San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, USA, 8-12 December 2015 The 38th annual San Antonio Breast Cancer Symposium was convened in San Antonio (TX, USA) on 8-12 December 2015. More than 7000 clinicians and scientists from around the world participated in the symposium, which featured a range of presentations and keynote talks pertaining to breast cancer screening, prevention, loco-regional and systemic therapies. This two-part report highlights a selection of important studies presented at this premier breast cancer event with part 1 focusing on radiotherapy treatment, translational approaches to immunotherapy and longer term cardiotoxicity from anti-HER2 therapies. The second part of this report will discuss a range of topics including de-escalation of chemotherapy regimens in luminal A tumors, the prognostic relevance of circulating tumor cells, the optimum treatment of triple-negative breast cancer and shifting attitudes to primary surgical treatment. PMID- 26880384 TI - The role of neoadjuvant therapy in pancreatic cancer: a review. AB - Controversy remains regarding neoadjuvant approaches in the treatment of pancreatic cancer. Neoadjuvant therapy has several potential advantages over adjuvant therapy including earlier delivery of systemic treatment, in vivo assessment of response, increased resectability rate in borderline resectable patients and increased margin-negative resection rate. At present, there are no randomized data favoring neoadjuvant over adjuvant therapy and multiple neoadjuvant approaches are under investigation. Combination chemotherapy regimens including 5-fluorouracil, irinotecan and oxaliplatin, gemcitabine with or without abraxane, or docetaxel and capecitabine have been used in the neoadjuvant setting. Radiation and chemoradiation have also been incorporated into neoadjuvant strategies, and delivery of alternative fractionation regimens is being explored. This review provides an overview of neoadjuvant therapies for pancreatic cancer. PMID- 26880387 TI - Highlights of the San Antonio Breast Cancer Symposium 2015: part 1. AB - 38th San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 8-12 December 2015 The 38th annual San Antonio Breast Cancer Symposium (SABCS) was convened in San Antonio (TX, USA) on 8-12 December 2015. More than 7000 clinicians and scientists from around the world participated in the symposium, which featured a range of presentations and keynote talks pertaining to breast cancer screening, prevention, loco-regional and systemic therapies. This two-part report highlights a selection of important studies presented at this premier breast cancer event with part 1 focusing on radiotherapy treatment, translational approaches to immunotherapy and longer term cardiotoxicity from anti-HER2 therapies. The second part of this report will discuss a range of topics including de-escalation of chemotherapy regimens in luminal A tumors, the prognostic relevance of circulating tumor cells, the optimum treatment of triple-negative breast cancer and shifting attitudes to primary surgical treatment. PMID- 26880388 TI - Relative cytotoxic potencies and cell death mechanisms of alpha1 -adrenoceptor antagonists in prostate cancer cell lines. AB - BACKGROUND: Some alpha1 -adrenoceptor antagonists possess anti-cancer actions that are independent of alpha1 -adrenoceptors and the aim of these studies was to assess the relative cytotoxic potencies of alpha1 -adrenoceptor antagonists and the mechanisms involved in these actions. METHODS: PC-3 and LNCap human prostate cancer cells were exposed to alpha1 -adrenoceptor antagonists (0.01-100 MUM) and cell survival assessed after 24-72 hr. The levels of apoptosis, autophagy and stress related proteins were also determined. RESULTS: The relative cytotoxic potency order was prazosin = doxazosin > terazosin = silodosin = alfuzosin > tamsulosin on both cell types, but LNCaP cells were significantly more sensitive to these effects than PC-3 cells. Prazosin and doxazosin increased levels of apoptotsis and autophagy in both cell lines, and activated EphA2 receptors in PC 3 cells. Autophagy contributed to survival of LNCaP, but promoted cell death in PC-3 cells. Treatment with prazosin (30 MUM) altered the expression of several cell stress-related proteins: elevating phospho-p38alpha and reducing S6 kinase in both cell lines. Surprisingly some proteins were differentially affected in the two prostate cancer cell lines: Akt and p27 increasing and HIF-1alpha decreasing in LNCap cells but not PC-3, while ADAMTS1 was increased in PC-3 cells only. CONCLUSIONS: Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells. PMID- 26880389 TI - Hybrid Closed-Loop Insulin Delivery in Type 1 Diabetes During Supervised Outpatient Conditions. AB - BACKGROUND: Efficacy and safety of the Medtronic Hybrid Closed-Loop (HCL) system were tested in subjects with type 1 diabetes in a supervised outpatient setting. METHODS: The HCL system is a prototype research platform that includes a sensor augmented insulin pump in communication with a control algorithm housed on an Android-based cellular device. Nine subjects with type 1 diabetes (5 female, mean age 53.3 years, mean A1C 7.2%) underwent 9 studies totaling 571 hours of closed loop control using either default or personalized parameters. The system required meal announcements with estimates of carbohydrate (CHO) intake that were based on metabolic kitchen quantification (MK), dietician estimates (D), or subject estimates (Control). Postprandial glycemia was compared for MK, D, and Control meals. RESULTS: The overall sensor glucose mean was 145 +/- 43, the overall percentage time in the range 70-180 mg/dL was 80%, the overall percentage time <70 mg/dL was 0.79%. Compared to intervals of default parameter use (225 hours), intervals of personalized parameter use (346 hours), sensor glucose mean was 158 +/- 49 and 137 +/- 37 mg/dL (P < .001), respectively, and included more time in range (87% vs 68%) and less time below range (0.54% vs 1.18%). Most subjects underestimated the CHO content of meals, but postprandial glycemia was not significantly different between MK and matched Control meals (P = .16) or between D and matched Control meals (P = .76). There were no episodes of severe hypoglycemia. CONCLUSIONS: The HCL system was efficacious and safe during this study. Personally adapted HCL parameters were associated with more time in range and less time below range than default parameters. Accurate estimates of meal CHO did not contribute to improved postprandial glycemia. PMID- 26880390 TI - Nonadjunctive Use of Continuous Glucose Monitoring for Diabetes Treatment Decisions. AB - While self-monitoring of blood glucose (SMBG) is the current standard used by people with diabetes to manage glucose levels, recent improvements in accuracy of continuous glucose monitoring (CGM) technology are making it very likely that diabetes-related treatment decisions will soon be made based on CGM values alone. Nonadjunctive use of CGM will lead to a paradigm shift in how patients manage their glucose levels and will require substantial changes in how care providers educate their patients, monitor their progress, and provide feedback to help them manage their diabetes. The approval to use CGM nonadjunctively is also a critical step in the pathway toward FDA approval of an artificial pancreas system, which is further expected to transform diabetes care for people with type 1 diabetes. In this article, we discuss how nonadjunctive CGM is expected to soon replace routine SMBG and how this new usage scenario is expected to transform health outcomes and patient care. PMID- 26880391 TI - Glucose Variability: Comparison of Different Indices During Continuous Glucose Monitoring in Diabetic Patients. AB - BACKGROUND: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. METHODS: Glucose variability was studied in 150 insulin treated diabetic patients (46% men, 42% type 1 diabetes, age 52 +/- 11 years) using a continuous glucose monitoring system (668 +/- 564 glucose values; mean glucose value 173 +/- 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). RESULTS: CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. CONCLUSIONS: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients. PMID- 26880393 TI - Visible light response, electrical transport, and amorphization in compressed organolead iodine perovskites. AB - Recent scientific advances on organic-inorganic hybrid perovskites are mainly focused on the improvement of power conversion efficiency. So far, how compression tunes their electronic and structural properties remains less understood. By combining in situ photocurrent, impedance spectroscopy, and X-ray diffraction (XRD) measurements, we have studied the electrical transport and structural properties of compressed CH3NH3PbI3 (MAPbI3) nanorods. The visible light response of MAPbI3 remains robust below 3 GPa while it is suppressed when it becomes amorphous. Pressure-induced electrical transport properties of MAPbI3 including resistance, relaxation frequency, and relative permittivity have been investigated under pressure up to 8.5 GPa by in situ impedance spectroscopy measurements. These results indicate that the discontinuous changes of these physical parameters occur around the structural phase transition pressure. The XRD studies of MAPbI3 under high pressure up to 20.9 GPa show that a phase transformation below 0.7 GPa, could be attributed to the tilting and distortion of PbI6 octahedra. And pressure-induced amorphization is reversible at a low density amorphous state but irreversible at a relatively higher density state. Furthermore, the MAPbI3 nanorods crush into nanopieces around 0.9 GPa which helps us to explain why the mixed phase of tetragonal and orthorhombic was observed at 0.5 GPa. The pressure modulated changes of electrical transport and visible light response properties open up a new approach for exploring CH3NH3PbI3-based photo electronic applications. PMID- 26880394 TI - Toll-like receptor-mediated immune response inhibits prion propagation. AB - Prion diseases are progressive neurodegenerative disorders affecting humans and various mammals. The prominent neuropathological change in prion diseases is neuroinflammation characterized by activation of neuroglia surrounding prion deposition. The cause and effect of this cellular response, however, is unclear. We investigated innate immune defenses against prion infection using primary mixed neuronal and glial cultures. Conditional prion propagation occurred in glial cultures depending on their immune status. Preconditioning of the cells with the toll-like receptor (TLR) ligand, lipopolysaccharide, resulted in a reduction in prion propagation, whereas suppression of the immune responses with the synthetic glucocorticoid, dexamethasone, increased prion propagation. In response to recombinant prion fibrils, glial cells up-regulated TLRs (TLR1 and TLR2) expression and secreted cytokines (tumor necrosis factor-alpha, interleukin 1beta, interleukin-6, granulocyte-macrophage colony-stimulating factor, and interferon-beta). Preconditioning of neuronal and glial cultures with recombinant prion fibrils inhibited prion replication and altered microglial and astrocytic populations. Our results provide evidence that, in early stages of prion infection, glial cells respond to prion infection through TLR-mediated innate immunity. PMID- 26880392 TI - The Potential Cost Implications of Averting Severe Hypoglycemic Events Requiring Hospitalization in High-Risk Adults With Type 1 Diabetes Using Real-Time Continuous Glucose Monitoring. AB - BACKGROUND: Severe hypoglycemia remains a major barrier to optimal diabetes management and places a high burden on the US health care system due to the high costs of hypoglycemia-related emergency visits and hospitalizations. Patients with type 1 diabetes (T1DM) who have hypoglycemia unawareness are at a particularly high risk for severe hypoglycemia, the incidence of which may be reduced by the use of real-time continuous glucose monitoring (RT-CGM). METHODS: We performed a cost calculation using values of key parameters derived from various published sources to examine the potential cost implications of standalone RT-CGM as a tool for reducing rates of severe hypoglycemia requiring hospitalization in adult patients with T1DM who have hypoglycemia unawareness. RESULTS: In a hypothetical commercial health plan with 10 million members aged 18 64 years, 9.3% (930 000) are expected to have diagnosed diabetes, with approximately 5% (46 500) having T1DM, of whom approximately 20% (9300) have hypoglycemia unawareness. RT-CGM was estimated to reduce the cost of annual hypoglycemia-related hospitalizations in this select population by $54 369 000, yielding an estimated net cost savings of $8 799 000 to $12 519 000 and a savings of $946 to $1346 per patient. CONCLUSION: This article presents a cost calculation based on available data from multiple sources showing that RT-CGM has the potential to reduce short-term health care costs by averting severe hypoglycemic events requiring hospitalization in a select high-risk population. Prospective, randomized studies that are adequately powered and specifically enroll patients at high risk for severe hypoglycemia are needed to confirm that RT-CGM significantly reduces the incidence of these costly events. PMID- 26880395 TI - Risking Life and Limb: Estimating a Measure of Medical Care Economic Risk and Considering its Implications. AB - This paper considers the risk of incurring future medical expenditures in light of a family's resources available to pay for those expenditures as well as their choice of health insurance. We model non-premium medical out-of-pocket expenditures and use the estimates from our model to develop a prospective measure of medical care economic risk estimating the proportion of families who are at risk of incurring high non-premium out-of-pocket medical care expenses in relation to its resources. We further use the estimates from our model to compare the extent to which different types of insurance mitigate the risk of incurring non-premium expenditures by providing for increased utilization of medical care. We find that while 21.3% of families lack the resources to pay for the median expenditures for their insurance type, 42.4% lack the resources to pay for the 99th percentile of expenditures for their insurance type. We also find the mediating effect of insurance on non-premium expenditures to outweigh the associated premium expense for expenditures above $1804 for employer-sponsored insurance and $4337 for direct purchase insurance for those younger than age 65; and above $12 118 of expenditures for Medicare supplementary plans for those aged 65 or older. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26880396 TI - Can No-Report Paradigms Extract True Correlates of Consciousness? PMID- 26880397 TI - Thermal Tolerances of the Spotted-Wing Drosophila Drosophila suzukii (Diptera: Drosophilidae). AB - The spotted-wing drosophila (Drosophila suzukii Matsumura) is an invasive species of Asian origin that is now widely distributed in North America and Europe. Because of the female's serrated ovipositor, eggs are laid in preharvest fruit, causing large economic losses in cultivated berries and stone fruit. Modeling D. suzukii population dynamics and potential distribution will require information on its thermal tolerance. Large summer populations have been found in regions with severe winter conditions, though little is known about responses to prolonged low-temperature exposure. We used controlled chambers to examine D. suzukii fecundity, development rate, and mortality across a range of temperatures encompassing the upper and lower thresholds (5-35 degrees C). Optimal temperatures (Topt) were found to be 28.2 degrees C for the development of the egg-to-adult stage, and 22.9 degrees C for reproductive output. No adult eclosion occurred below 8.1 degrees C (Tlower) or above 30.9 degrees C (Tupper). We also investigated survival outcomes following prolonged (42-d) low-temperature exposure to a simulated cold winter (-5, -3, -1, 1, 3, and 5 degrees C). Adult survival was dependent on temperature, with a mean LT50 of 4.9 degrees C. There were no effects of sex, mating status, geographic strain, and photoperiod preexposure on overwintering survival. Thirty-eight percent of females that were mated prior, but not after, prolonged low-temperature exposure produced viable offspring, suggesting that this species may undergo sperm storage. This study provides data on the thermal tolerances of D. suzukii, which can be used for models of D. suzukii population dynamics, degree-day, and distribution models. PMID- 26880398 TI - Modulation of Juvenile Hormone Esterase Gene Expression Against Development of Plutella xylostella (Lepidoptera: Plutellidae). AB - The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is a widespread and destructive pest of cruciferous crops. Owing to its increasing resistance to conventional pesticides, new strategies need to be developed for diamondback moth control. Here, we investigated factors that modulate juvenile hormone esterase (JHE) activity and jhe (Px004817) transcription, and determined the effects of these factors on subsequent growth and development in diamondback moth. Starvation inhibited JHE activity and jhe transcription, increased mortality, and decreased the rate of molting from the third- to the fourth-instar stages. Larvae kept at 32 degrees C molted earlier and showed increased JHE activity and jhe transcription after 24-h treatment. Exposure to 1,325 mg/liter OTFP (3-octylthio-1,1,1-trifluoro-2-propanone) delayed molting and pupation, increased pupal weight, and decreased JHE activity and jhe transcription at both 24 and 48 h. Treatment with 500 mg/liter pyriproxyfen delayed molting, completely suppressed pupation, and significantly increased JHE activity at 48 h and jhe transcription at 24 and 48 h. A combination of OTFP (1,325 mg/liter) and pyriproxyfen (500 mg/liter) induced the highest mortality, delayed molting, completely suppressed pupation, and significantly increased JHE activity at 48 h and jhe transcription at 24 and 48 h. These effects on JHE activity and jhe transcription were similar to those in insects treated only with pyriproxyfen. The results demonstrated that JHE and jhe (Px004817) were involved in the responses of diamondback moth to external modulators and caused changes in growth and development. The combination of OTFP and pyriproxyfen increased the effectiveness of action against diamondback moth. PMID- 26880399 TI - The use of nonsteroidal anti-inflammatory drugs and analgesics by liver transplant recipients. AB - AIMS AND OBJECTIVES: This study aimed to assess the reasons and the frequency of the use of over-the-counter (OTC) nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics by liver transplant recipients (LTR). Patient awareness of possible drug-related side-effects was also assessed. BACKGROUND: NSAIDs and analgesics available without prescription belong to the most commonly used class of drugs. However, use of these drugs might be complicated by toxic adverse effects (AEs). Patients at risk for AEs include the transplant recipients. DESIGN/METHODS: This was a descriptive study. An anonymous survey was carried out in 73 randomly selected LTR, who represented 10% of all LTR at our centre. RESULTS: There were 64% of the patients who confirmed taking NSAIDs or analgesics; 16% of these patients took these drugs at least several times a week and 10% took them daily. For 39% of patients, the only way to manage their pain were OTC NSAIDs or analgesics. As many as 36% of patients were unaware of the risks associated with the use of these drugs. Ninety per cent of LTR consider physicians the most trusted source of drugs information. CONCLUSIONS: Our study shows that two-thirds of LTR take OTC NSAIDs or analgesics and one-third are unaware of the AEs associated with these drugs. Therefore, both transplant nurses and doctors should educate their patients about the use and possible AE of these drugs. RELEVANCE TO CLINICAL PRACTICE: Considering the high NSAIDs consumption rates, the side effects of these drugs should always be suspected. Especially in patients taking these drugs and referring to medical advisors with specific symptoms, such as: abdominal pain, anaemia, elevated serum creatinine concentration or liver enzymes activity. Awareness of the scale of the problem enables health professionals to cooperate in educating patients. Such practices may reduce uncontrolled abuse of these drugs and related health care costs. PMID- 26880400 TI - Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors. AB - The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets. We compared the results from NGS and CMA data from 60 lung and 51 colorectal tumors. From CMA analysis, 33% were amplified, 89% showed gains, 75% showed losses and 41% demonstrated loss of heterozygosity; pathogenic variants were identified in 81% of colon and 67% lung specimens through NGS. KRAS mutations commonly occurred with loss in TP53 and there was significant loss of BRCA1 and NF1 among male patients with lung cancer. For clinically actionable targets, 23% had targetable CNVs when no pathogenic variants were detected by NGS. The data thus indicate that combining the two approaches provides significant benefit in a routine clinical setting not available by NGS alone. PMID- 26880401 TI - Persistent inflammation and recovery after intensive care: A systematic review. AB - PURPOSE: Physical weakness is common after critical illness; however, it is not clear how best to treat it. Inflammation characterizes critical illness, is associated with loss of muscle mass during critical illness, and potentially modifies post-intensive care unit (ICU) recovery. We sought to identify published reports on the prevalence of systemic inflammation after critical illness and its association with physical recovery. METHODS: This is a systematic review of the literature from MEDLINE, EMBASE, CINAHL, CPCI-SSH, and CPCI-S from January 1982 to December 2011. RESULTS: From 7433 references, 207 full-text articles were reviewed, 57 were eligible, and 22 were included. Inflammation was present in most patients at ICU discharge according to C-reactive protein concentration (range, 70%-100%), procalcitonin (range, 89%-100%), tumor necrosis factor alpha (100%), and systemic inflammatory response syndrome criteria (range, 92%-95%). Fewer patients had elevated myeloperoxidase concentrations (range, 0%-56%). At hospital discharge, 9 (90%) of 10 chronic obstructive pulmonary disease patients had elevated C-reactive protein. No studies tested the association between inflammation and physical recovery. CONCLUSIONS: Inflammation is present in most patients at ICU discharge, but little is known or has been investigated about persistent inflammation after this time point. No studies have explored the relationship between persistent inflammation and physical recovery. Further research is proposed. PMID- 26880403 TI - The Uptake and Assembly of Alkanes within a Porous Nanocapsule in Water: New Information about Hydrophobic Confinement. AB - In Nature, enzymes provide hydrophobic cavities and channels for sequestering small alkanes or long-chain alkyl groups from water. Similarly, the porous metal oxide capsule [{Mo(VI) 6 O21 (H2 O)6 }12 {(Mo(V) 2 O4 )30 (L)29 (H2 O)2 }](41-) (L=propionate ligand) features distinct domains for sequestering differently sized alkanes (as in Nature) as well as internal dimensions suitable for multi alkane clustering. The ethyl tails of the 29 endohedrally coordinated ligands, L, form a spherical, hydrophobic "shell", while their methyl end groups generate a hydrophobic cavity with a diameter of 11 A at the center of the capsule. As such, C7 to C3 straight-chain alkanes are tightly intercalated between the ethyl tails, giving assemblies containing 90 to 110 methyl and methylene units, whereas two or three ethane molecules reside in the central cavity of the capsule, where they are free to rotate rapidly, a phenomenon never before observed for the uptake of alkanes from water by molecular cages or containers. PMID- 26880402 TI - Eosinophil resistance to glucocorticoid-induced apoptosis is mediated by the transcription factor NFIL3. AB - The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired pro-apoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5 treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that (1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and (2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID- 26880404 TI - Soluble galectin-3 is associated with premature myocardial infarction. AB - BACKGROUND: Inflammatory responses are pivotal in the initiation and development of premature atherosclerotic lesions. Galectin-3 represents a valuable biomarker for both progression and destabilization of atherosclerotic lesions. This study aims to assess the involvement of galectin-3 in premature myocardial infarction. DESIGN: In this multicentre case-control study, we assessed circulating galectin 3 levels in 144 patients comprising 72 consecutive survivors of acute myocardial infarction (<= 40 years) and 72 hospital controls frequency matched for age, gender and centre. RESULTS: Patients with acute myocardial infarction showed significantly higher galectin-3 levels as compared to controls in the acute phase of acute myocardial infarction (2552 +/- 1992 vs. 1666 +/- 829 pg/mL; P < 0.001) as well as in the stable phase 1 year after the index event (3692 +/- 1774 vs. 1666 +/- 829 pg/mL; P < 0.001). Circulating galectin-3 was significantly and independently associated with premature myocardial infarction in the logistic regression analysis (acute phase: adj. OR per 1-SD change 2.03, 95% CI 1.30-3.19; P = 0.002; stable phase: adj. OR of 6.54 (95% CI 2.56-16.68; P < 0.001). Moreover, we observed a significant correlation between circulating galectin-3 and leucocyte count (r = 0.35, P < 0.001), non-HDL cholesterol (r = 0.23, P = 0.014) and HDL cholesterol (r = -0.29, P = 0.002). CONCLUSION: We demonstrated that elevated levels of circulating galectin-3 are strongly associated with premature myocardial infarction. Galectin-3 might serve as link between dyslipidaemia as driving force of plaque formation with inflammation as initiator of plaque rupture in patients with premature acute myocardial infarction. PMID- 26880405 TI - Potential intake of vitamins "A" and "D" through branded intravenous lipid emulsions: Liquid Chromatography-Tandem Mass Spectrometry Analysis. AB - No data exist for vitamin A group and vitamin D2/D3 content in branded intravenous lipid emulsions (ILEs). Our goal is to evaluate and quantify their concentrations in different ILEs to assess whether they are clinically relevant. Analyses were carried out in triplicates on six ILEs: 1) 30% soybean oil-based, 2) 20% olive-soybean oil based, 3) 10 + 10% soybean - MCT coconut oil based, 4) 20% soybean-olive-MCT-fish oil based, 5) 20% soybean-MCT-fish oil based and 6) 10% pure fish oil based, respectively. Retinol group (vitamin A) and ergo-chole calciferol (vitamin D2/D3) were analyzed and quantified by a quali-quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) method after potassium hydroxide alkaline hydrolysis, hexane extraction, reverse phase-liquid chromatography and specific multiple-reaction-monitoring (MRM) detection. On average, measured retinol content was in the range of 200-1000 MUg/L in ILEs (1,2, and 3), whereas it was higher (1000-2000 MUg/L) in the ILEs containing fish oil. Vitamin D content was in the range of 1-10 MUg/L in the fish-oil based ILEs, but undetectable in those ILEs containing purely vegetable oils. This study shows that vitamin A and D contents are variably present in ILEs based on their different lipid sources. Both contents should be explicitly mentioned in the products. PMID- 26880406 TI - Reply - Letter to the Editor - Pulmonary rehabilitation and oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate for bronchiectasis participants: A prospective, randomised study. PMID- 26880407 TI - The Usefulness of Chest X-Rays for T1a Renal Cell Carcinoma Surveillance. AB - PURPOSE: The overall incidence of pulmonary metastasis of T1 renal cell carcinoma is low. We evaluated the usefulness of chest x-rays based on the current AUA (American Urological Association) guidelines and NCCN Guidelines(r) for T1a renal cell carcinoma surveillance. MATERIALS AND METHODS: Between 2006 and 2012, 258 patients with T1a renal cell carcinoma were treated with partial nephrectomy, radical nephrectomy or radio frequency ablation with surveillance followup at our institution. A retrospective chart review was performed to identify demographics, pathological findings and surveillance records. The primary outcome was the incidence of asymptomatic pulmonary recurrences diagnosed by chest x-ray in cases of T1a disease. Our secondary outcome was a comparison of diagnoses by treatment modality (partial nephrectomy, radical nephrectomy or radio frequency ablation). RESULTS: Pulmonary metastases developed in 3 of 258 patients (1.2%) but only 1 (0.4%) was diagnosed by standard chest x-ray surveillance. Median followup in the entire cohort was 36 months (range 6 to 152) and 193 of 258 patients (75%) had greater than 24 months of followup. A mean of 3.3 surveillance chest x-rays were completed per patient. When assessed by treatment type, there was no significant difference in the recurrence rate for partial nephrectomy (0 of 191 cases), radical nephrectomy (0 of 22) or radio frequency ablation (1 of 45 or 2.2%) (p = 0.09). CONCLUSIONS: Chest x-rays are a low yield diagnostic tool for detecting pulmonary metastasis in patients treated for T1a renal cel carcinoma. Treatment mode does not appear to influence the need for chest x-ray surveillance. PMID- 26880408 TI - Prostate Cancer Diagnosis on Repeat Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy of Benign Lesions: Recommendations for Repeat Sampling. AB - PURPOSE: Urologists face a dilemma when a lesion identified on multiparametric magnetic resonance imaging is benign on image guided fusion biopsy. We investigated the detection rate of prostate cancer on repeat fusion biopsy in multiparametric magnetic resonance imaging lesions initially found to be pathologically benign on fusion biopsy. MATERIALS AND METHODS: We reviewed the records of all patients from 2007 to 2014 who underwent multiparametric magnetic resonance imaging and image guided fusion biopsy. We identified men who underwent rebiopsy of the same discrete lesion after initial fusion biopsy results were benign. Data were documented on a per lesion basis. We manually reviewed UroNav system (Invivo, Gainesville, Florida) needle tracking to verify accurate image registration. Multivariate analysis was used to identify clinical and imaging factors predictive of prostate cancer detection at repeat fusion biopsy. RESULTS: A total of 131 unique lesions were rebiopsied in 90 patients. Of these 131 resampled lesions 21 (16%) showed prostate cancer, which in 13 (61.9%) was Gleason 3 + 3. On multivariate analysis only lesion growth on repeat multiparametric magnetic resonance imaging was significantly associated with prostate cancer detection at repeat biopsy (HR 3.274, 95% CI 1.205-8.896, p = 0.02). CONCLUSIONS: Pathologically benign multiparametric magnetic resonance imaging lesions on initial image guided fusion biopsy are rarely found to harbor clinically significant prostate cancer on repeat biopsy. When prostate cancer was identified, most disease was low risk. An increase in lesion diameter was an independent predictor of prostate cancer detection. While these data are retrospective, they may provide some confidence in the reliability of negative initial image guided fusion biopsies despite a positive multiparametric magnetic resonance imaging finding. PMID- 26880409 TI - Recurrent Urinary Tract Infections Due to Bacterial Persistence or Reinfection in Women-Does This Factor Impact Upper Tract Imaging Findings? AB - PURPOSE: We compared the rates of upper tract imaging abnormalities of recurrent urinary tract infections due to bacterial persistence or reinfection. MATERIALS AND METHODS: Following institutional review board approval we reviewed a prospectively maintained database of women with documented recurrent urinary tract infections (3 or more per year) and trigonitis. We searched for demographic data, urine culture findings and findings on radiology interpreted upper tract imaging, including renal ultrasound, computerized tomography or excretory urogram. Patients with irretrievable images, absent or incomplete urine culture results for review, no imaging performed, an obvious source of recurrent urinary tract infections or a history of pyelonephritis were excluded from analysis. RESULTS: Of 289 women from 2006 to 2014 with symptomatic recurrent urinary tract infections 116 met study inclusion criteria. Mean +/- SD age was 65.0 +/- 14.4 years. Of the women 95% were white and 81% were postmenopausal. Almost a third were sexually active and none had prolapse stage 2 or greater. Of the 116 women 48 (41%) had persistent and 68 (59%) had reinfection recurrent urinary tract infection. Imaging included ultrasound in 52 patients, computerized tomography in 26, ultrasound and computerized tomography in 31, and excretory urogram with ultrasound/computerized tomography in 7. Of the total of 58 imaging findings in 55 women 57 (98%) were noncontributory. One case (0.9%) of mild hydronephrosis was noted in the persistent recurrent urinary tract infection group but it was not related to any clinical parameters. Escherichia coli was the dominant bacteria in 71% of persistent and 47% of reinfection recurrent urinary tract infections in the most recently reported urine culture. CONCLUSIONS: This study reaffirms that upper tract imaging is not indicated for bacterial reinfection, recurrent urinary tract infections. However, the same conclusion can be extended to recurrent urinary tract infections secondary to bacterial persistence, thus, questioning the routine practice of upper tract studies in white postmenopausal women with recurrent urinary tract infections and trigonitis. PMID- 26880410 TI - Promising Effects of a Novel EP2 and EP3 Receptor Dual Agonist, ONO-8055, on Neurogenic Underactive Bladder in a Rat Lumbar Canal Stenosis Model. AB - PURPOSE: We investigated whether the novel EP (prostaglandin E2) receptor agonist ONO-8055 would improve the lower urinary tract dysfunction of neurogenic underactive bladder in a rat lumbar spinal canal stenosis model. MATERIALS AND METHODS: First, we studied the agonistic effect of ONO-8055 on EP receptors in EP receptor expressing CHO (Chinese hamster ovary) cells using the increase in the intracellular calcium level and intracellular cAMP (cyclic adenosine monophosphate) production as indicators of receptor activation. The effects of ONO-8055 on bladder and urethral strips from normal rats were then investigated. Finally, the effects of ONO-8055 on bladder and urethral function in rats with lumbar spinal canal stenosis were evaluated by awake cystometry and intraurethral perfusion pressure, respectively. The effects of tamsulosin and distigmine on urethral pressure were also evaluated. RESULTS: ONO-8055 is a highly potent and selective agonist for EP2 and EP3 receptors on CHO cells. While this compound contracted bladder strips, it relaxed urethral strips. Awake cystometry showed that ONO-8055 significantly decreased bladder capacity, post-void residual urine and voiding pressure. Compared with vehicle, tamsulosin and ONO-8055 significantly decreased urethral pressure. CONCLUSIONS: ONO-8055 decreased post void residual urine, probably by decreasing bladder capacity. The decrease in voiding pressure probably resulted from the lowered urethral pressure due to relaxation of the urethra. Thus, the novel EP2 and EP3 receptor dual agonist ONO 8055 has the potential to improve neurogenic underactive bladder. PMID- 26880411 TI - Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits. AB - PURPOSE: Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation. MATERIALS AND METHODS: Poly-L-lactic acid and polyurethane meshes were electrospun to be compared to commercially available polypropylene and polyvinylidene fluoride meshes. A total of 40 immunocompetent full-thickness abdominal wall defect rabbit models were used, including 8 in each of the poly-L-lactic acid, polyurethane, polyvinylidene fluoride and polypropylene experimental groups, and sham controls. Two 20 mm defects were created per animal and primarily repaired. The experimental groups then underwent onlay of each repair material while sham controls did not. Four rabbits per group were sacrificed at days 30 and 90. Abdominal wall specimens containing the defect with or without repair material were explanted to be assessed by histology (hematoxylin and eosin staining, and immunohistochemistry) and biomechanical testing at 30 and 90 days. RESULTS: At 90 days of implantation tissues repaired with all 4 materials showed biomechanical properties without significant differences. However, polypropylene and polyvinylidene fluoride meshes demonstrated a sustained chronic inflammatory response profile by 90 days. In contrast, poly-L-lactic acid and polyurethane meshes integrated well into host tissues with a decreased inflammatory response, indicative of constructive remodeling. CONCLUSIONS: Poly-L-lactic acid and polyurethane alternative materials achieved better host integration in rabbit models than current synthetic repair materials. PMID- 26880412 TI - Hydrogen Sulfide Induced Erythropoietin Synthesis is Regulated by HIF Proteins. AB - PURPOSE: Anemia of end stage renal disease affects 90% of patients on hemodialysis and it is a tremendous concern of patients and health care providers. Renal disease creates a state of renal hypoxia, which may contribute to a lack of erythropoietin production from the kidney when low oxygen levels are sensed. This necessitates the use of exogenous erythropoietin preparations. MATERIALS AND METHODS: Recent evidence suggests that endogenously derived hydrogen sulfide may mediate oxygen sensing in tissues. Given the known involvement of other small molecules such as nitric oxide in erythropoietin production and the observation of decreased urinary H2S levels in patients with renal failure, we postulated that H2S may be the primary mediator of erythropoietin production during hypoxia. PK1, 786-O and Hep3B cells were incubated in hypoxia (1% O2) for 24 hours. Hypoxic cells were treated with the H2S donor GYY 4137 and the H2S inhibitor hydroxylamine. Following hypoxia erythropoietin, HIF-1alpha, HIF-2alpha and CBS expression was measured by quantitative real-time polymerase chain reaction and Western blot. RESULTS: Hydroxylamine administration led to a significant decrease in erythropoietin, HIF 1alpha, HIF-2alpha and CBS protein levels during hypoxia. This was rescued by administration of GYY 4137 for erythropoietin, CBS and HIF-2alpha. Additionally, CSE -/- mice placed in hypoxia for 72 hours showed decreased renal erythropoietin production compared to wild-type mice. CONCLUSIONS: These data suggest previously undocumented interplay of the production and action of H2S during hypoxia with subsequent erythropoietin production. The use of novel hydrogen sulfide donors could represent an alternative to standard therapies of anemia of renal failure. PMID- 26880413 TI - A Pilot Study to Evaluate the Role of Magnetic Resonance Imaging for Prostate Cancer Screening in the General Population. AB - PURPOSE: To our knowledge the role of magnetic resonance imaging as a first line screening test for prostate cancer is unknown. We performed a pilot study to evaluate the feasibility of prostate magnetic resonance imaging as the primary screening test for prostate cancer. MATERIALS AND METHODS: We recruited unselected men from the general population. Prostate multiparametric magnetic resonance imaging and random or targeted biopsies were performed in all patients, in addition to prostate specific antigen testing. We compared the performance of prostate magnetic resonance imaging and prostate specific antigen test results to predict prostate cancer. RESULTS: Of the 47 recruited patients 18 (38.3%) had cancer while 29 (61.7%) had no evidence of cancer. The adjusted OR of prostate cancer was significantly higher for magnetic resonance imaging score than for prostate specific antigen level (2.7, 95% CI 1.4-5.4, p = 0.004 vs 1.1, 95% CI 0.9-1.4, p = 0.21). Among the 30 patients with a normal prostate specific antigen (less than 4.0 ng/ml) the positive predictive value in those with a magnetic resonance imaging score of 4 or more was 66.7% (6 of 9) and the negative predictive value in those with a magnetic resonance imaging score of 3 or less was 85.7% (18 of 21, p = 0.004). CONCLUSIONS: In this pilot study we determined the feasibility of using multiparametric prostate magnetic resonance imaging as the primary screening test for prostate cancer. Initial results showed that prostate magnetic resonance imaging was better to predict prostate cancer than prostate specific antigen in an unselected sample of the general population. PMID- 26880414 TI - Use of Pediatric Open, Laparoscopic and Robot-Assisted Laparoscopic Ureteral Reimplantation in the United States: 2000 to 2012. AB - PURPOSE: We characterize the use of pediatric open, laparoscopic and robot assisted laparoscopic ureteral reimplantation in the United States from 2000 to 2012. MATERIALS AND METHODS: We used the Kids' Inpatient Database to identify patients who underwent ureteral reimplantation for primary vesicoureteral reflux. Before 2009 laparoscopic ureteral reimplantion and robot-assisted laparoscopic ureteral reimplantation were referred to together as minimally invasive ureteral reimplantation. A detailed analysis of open vs robot-assisted laparoscopic ureteral reimplantation was performed for 2009 and 2012. RESULTS: A total of 14,581 ureteral reimplantations were performed. The number of ureteral reimplantations yearly decreased by 14.3%. However, the proportion of minimally invasive ureteral reimplantations increased from 0.3% to 6.3%. A total of 125 robot-assisted laparoscopic ureteral reimplantations were performed in 2012 (81.2% of minimally invasive ureteral reimplantations), representing 5.1% of all ureteral reimplantations, compared to 3.8% in 2009. In 2009 and 2012 mean +/- SD patient age was 5.7 +/- 3.6 years for robot-assisted laparoscopic ureteral reimplantation and 4.3 +/- 3.3 years for open reimplantation (p <0.0001). Mean +/ SD length of hospitalization was 1.6 +/- 1.3 days for robot-assisted laparoscopic ureteral reimplantation and 2.4 +/- 2.6 for open reimplantation (p <0.0001). Median charges were $22,703 for open and $32,409 for robot-assisted laparoscopic ureteral reimplantation (p <0.0001). These relationships maintained significance on multivariate analyses. On multivariate analysis robot-assisted laparoscopic ureteral reimplantation use was associated with public insurance status (p = 0.04) and geographic region outside of the southern United States (p = 0.02). Only 50 of 456 hospitals used both approaches (open and robotic), and only 6 hospitals reported 5 or more robot-assisted laparoscopic ureteral reimplantations during 2012. CONCLUSIONS: Treatment of primary vesicoureteral reflux with ureteral reimplantation is decreasing. Robot-assisted laparoscopic ureteral reimplantation is becoming more prevalent but remains relatively uncommon. Length of stay is shorter for the robotic approach but the costs are higher. Nationally robot-assisted laparoscopic ureteral reimplantation appears to still be in the early phase of adoption and is clustered at a small number of hospitals. PMID- 26880416 TI - A remote coordination booster enhances the catalytic efficiency by accelerating the generation of an active catalyst. AB - A remote Ru(II)(terpy)2 unit incorporated in conjugation with the [NHC Ru(II)(para-cymene)] catalytic site, acts as a "coordination booster" for enhancing the catalytic efficiency to achieve excellent performance in selective oxidative scission of various carbon-carbon multiple bonds to the corresponding aldehydes, ketones and diketones. Generation of an active catalyst via oxidative loss of para-cymene from the precatalyst was found to be accelerated by the "coordination booster" through the electronic effect. PMID- 26880415 TI - Anticipating the Unintended Consequences of Closing the Door on Physician Self Referral. AB - PURPOSE: While physician self-referral has been associated with increased health care use, the downstream effects of the practice remain poorly characterized. Accordingly we identified the relationship between urologist self-referral and downstream health care use in patients with urinary stone disease. MATERIALS AND METHODS: With urologist self-referral status as the exposure of interest, we performed a retrospective cohort study of Medicare beneficiaries from 2008 to 2010 to evaluate the relationship between self-referral and imaging intensity, risk of surgical treatment and time to surgical treatment for urinary stone disease. RESULTS: We identified dose dependent increases in computerized tomography use with increasing stratum of urologist self-referral. Compared to nonself-referring urologists, computerized tomography use was 1.19 times higher (95% CI 1.07-1.34) in episodes ascribed to intermediate frequency (5 to 9) and 1.32 times higher (95% CI 1.16-1.50) in episodes ascribed to high frequency (10+) self-referring urologists. Self-referral was inversely associated with risk of surgical treatment for stone disease. Specifically, patients treated by intermediate and high frequency self-referring urologists were less likely to undergo surgical treatment than those treated by nonself-referring urologists, with HR 0.84 (95% CI 0.71-0.99) and HR 0.81 (95% CI 0.66-0.99), respectively. We identified no statistically significant between-group differences in time to surgical treatment. CONCLUSIONS: Self-referral is associated with increased use of computerized tomography and with decreased use of surgery for stone disease. While policy efforts to further restrict physician self-referral may reduce the use of computerized tomography, they may also result in unintended consequences with respect to patterns of surgical care. PMID- 26880417 TI - [Malnutrition in children admitted to hospital. Results of a national survey]. AB - INTRODUCTION: Malnutrition on admission is closely related to a longer hospital stay and a higher morbidity. The prevalence of hospital malnutrition has been reported as almost as high as 50%, with 6% being the lowest. DHOSPE study investigates nutrition status in Spanish hospitals and its outcome during the hospital stay. PATIENTS AND METHODS: A longitudinal, multicentre, descriptive, cross-sectional study, with a short follow-up period was conducted in 32 hospitals during 2011. A total of 991 patients were included, with ages from 0 to 17 years. Each patient was measured at admission (weight, length, weight for length -W/L-, length for age -L/A-), and at 7 and 14 days. The STAMP nutritional screening tool was completed on admission. Anthropometric measurements were reported as z-score, and nutrition status classified according to W/L and L/A for acute and chronic malnutrition, respectively. RESULTS: The prevalence of malnutrition was 7.1% for moderate, and 0.7% for severe acute malnutrition. For chronic malnutrition, it was 2.7% moderate, and 1.4% severe. There were significant differences according to the underlying condition but not according to age. Results of STAMP show that around 75% of patients had a moderate to high risk of malnutrition. Nutritional status changed during admission for weight, as well as W/L and L/A. A worst nutritional status at admission and a higher STAMP score were positively correlated with the need for nutrition support. CONCLUSIONS: The prevalence of undernutrition was slightly lower (<8%) than previously reported, probably in relation to the variety of hospitals in the survey. Nevertheless, nutritional risk when evaluated with STAMP showed a high risk of malnutrition. PMID- 26880418 TI - Hypomethylation in Parkinson's disease: An epigenetic drug effect? PMID- 26880419 TI - Differential expression of beta-tubulin isotypes in different life stages of Parascaris spp after exposure to thiabendazole. AB - Anthelmintic resistance (AR) to macrocyclic lactones (ML) has been described in Parascaris of horses world-wide. In contrast, benzimidazoles (BZ) are still effective, although reduced efficacy to this drug class was recently reported. The mode of action of BZ is binding to beta-tubulin, which prevents polymerisation of microtubules. In this study, beta-tubulin gene expression of isotypes 1 and 2 was investigated at seven time points (0, 6, 24, 72, 96 and 120 h) during embryogenesis and in adult worms. In addition, an in ovo larval developmental test was developed to study beta-tubulin gene expression of both isotypes in parasacaris eggs after exposure to different concentrations of thiabendazole (TBZ) for five days at 25 degrees C. A strong pattern of differential expression of beta-tubulin and isotype 1 was observed in all stages, while isotype 2 expression was mainly found at an early phase of the embryogenesis. For isotype 1, a 5-fold increase was observed during the first 48 h, but gene expression gradually decreased after 72, 96 and 120 h. Isotype 2 was only expressed during the first 24h, followed by a 130-fold decrease at (time points) 72, 96 and 120 h. The in ovo larval developmental test, in which we exposed initially unembryonated eggs to increased concentrations of TBZ, did affect isotype 1 gene expression but not isotype 2. This assumes that each isotype has specific functions in different life stages. This is in agreement with the 'multi-tubulin' hypothesis, which states that different tubulin isotypes are required for specialised microtubule functions. Isotype 1 is the most likely drug target for BZs, as isotype 2 was only expressed at very low levels later in development. Increasing concentrations of TBZ altered beta-tubulin isotype 1 gene expression after exposure of the eggs for five days, but this was not seen for isotype 2. PMID- 26880420 TI - Human sex ratio at birth and residential proximity to nuclear facilities in France. AB - The possible detrimental genetic impact on humans living in the vicinity of nuclear facilities has been previously studied. We found evidence for an increase in the human secondary sex ratio (sex odds) within distances of up to 35km from nuclear facilities in Germany and Switzerland. Here, we extend our pilot investigations using new comprehensive data from France. The French data (1968 2011) account for 36,565 municipalities with 16,968,701 male and 16,145,925 female births. The overall sex ratio was 1.0510. Using linear and nonlinear logistic regression models with dummy variables coding for appropriately grouped municipalities, operation time periods, and corresponding spatiotemporal interactions, we consider the association between annual municipality-level birth sex ratios and minimum distances of municipalities from nuclear facilities. Within 35km from 28 nuclear sites in France, the sex ratio is increased relative to the rest of France with a sex odds ratio (SOR) of 1.0028, (95% CI: 1.0007, 1.0049). The detected association between municipalities' minimum distances from nuclear facilities and the sex ratio in France corroborates our findings for Germany and Switzerland. PMID- 26880422 TI - Rhodium-catalyzed ortho C-H bond activation of arylamines for the synthesis of quinoline carboxylates. AB - The rhodium catalyzed annulation of anilines with alkynic esters allowing for the high-yield synthesis of quinoline carboxylates with excellent regioselectivity is described. This unprecedented reaction employs either formic acid as the C1 source and reductant or copper(ii) as the oxidant and is proposed to proceed via rhodacycle of in situ generated amide and enamine ester followed by ortho C-H activation of arylamines with rhodium as the catalyst. PMID- 26880423 TI - A socio-ecological perspective of access to and acceptability of HIV/AIDS treatment and care services: a qualitative case study research. AB - BACKGROUND: Access to healthcare is an essential element of health development and a fundamental human right. While access to and acceptability of healthcare are complex concepts that interact with different socio-ecological factors (individual, community, institutional and policy), it is not known how these factors affect HIV care. This study investigated the impact of socio-ecological factors on access to and acceptability of HIV/AIDS treatment and care services (HATCS) in Wolaita Zone of Ethiopia. METHOD: Qualitative case study research was conducted in six woredas (districts). Focus group discussions (FGDs) were conducted with 68 participants in 11 groups (six with people using antiretroviral therapy (ART) and five with general community members). Key informant interviews (KIIs) were conducted with 28 people involved in HIV care, support services and health administration at different levels. Individual in-depth interviews (IDIs) were conducted with eight traditional healers and seven defaulters from (ART). NVIVO 10 was used to assist qualitative content data analysis. RESULTS: A total of 111 people participated in the study, of which 51 (45.9%) were male and 60 (54.1%) were female, while 58 (53.3%) and 53 (47.7%) were urban and rural residents, respectively. The factors that affect access to and acceptability of HATCS were categorized in four socio-ecological units of analysis: client-based factors (awareness, experiences, expectations, income, employment, family, HIV disclosure and food availability); community-based factors (care and support, stigma and discrimination and traditional healing); health facility-based factors (interactions with care providers, availability of care, quality of care, distance, affordability, logistics availability, follow up and service administration); and policy and standards (healthcare financing, service standards, implementation manuals and policy documents). CONCLUSIONS: A socio ecological perspective provides a useful framework to investigate the interplay among multilevel and interactive factors that impact on access to and acceptability of HATCS such as clients, community, institution and policy. Planners, resource allocators and implementers could consider these factors during planning, implementation and evaluation of HATCS. Further study is required to confirm the findings. PMID- 26880421 TI - A review of the proposed role of neutrophils in rodent amebic liver abscess models. AB - Host invasion by Entamoeba histolytica, the pathogenic agent of amebiasis, can lead to the development of amebic liver abscess (ALA). Due to the difficulty of exploring host and amebic factors involved in the pathogenesis of ALA in humans, most studies have been conducted with animal models (e.g., mice, gerbils, and hamsters). Histopathological findings reveal that the chronic phase of ALA in humans corresponds to lytic or liquefactive necrosis, whereas in rodent models there is granulomatous inflammation. However, the use of animal models has provided important information on molecules and mechanisms of the host/parasite interaction. Hence, the present review discusses the possible role of neutrophils in the effector immune response in ALA in rodents. Properly activated neutrophils are probably successful in eliminating amebas through oxidative and non-oxidative mechanisms, including neutrophil degranulation, the generation of free radicals (O2(-), H2O2, HOCl) and peroxynitrite, the activation of NADPH-oxidase and myeloperoxidase (MPO) enzymes, and the formation of neutrophil extracellular traps (NETs). On the other hand, if amebas are not eliminated in the early stages of infection, they trigger a prolonged and exaggerated inflammatory response that apparently causes ALAs. Genetic differences in animals and humans are likely to be key to a successful host immune response. PMID- 26880424 TI - Looking back on 40 years of JAN. PMID- 26880425 TI - STAN technology, surrogate outcomes and possible sources of bias. PMID- 26880426 TI - Preferences of Lay Persons and Dental Professionals Regarding the Recurring Esthetic Dental Proportion. AB - BACKGROUND: This study evaluated the preferences of dental professionals and lay persons with respect to the Recurring Esthetic Dental (RED) Proportion, an objective mathematical tool used in treatment planning the "apparent" widths of maxillary anterior teeth. MATERIALS AND METHODS: Stock dentofacial and facial images of a prototypical smiling male and female were digitally altered to demonstrate five different RED proportion relationships (0.62, 0.65, 0.70, 0.75, and 0.80). Four sets of the five altered images were presented to dental professionals and lay persons using a web-based survey site. The professional group included dentists and dental laboratory technicians. The lay group included anyone without previous dental education or experience. Study participants were asked to rank each series from most to least esthetic and their preferences were extracted from the data. RESULTS: Preference data from the five RED proportion relationships was consolidated into two categories: a narrow group including 0.62, 0.65, and 0.70 and a broad group including 0.75 and 0.80. Analysis shows that the level of professional training or experience does not play a significant role in the RED proportion preferences of study participants. Only in the prototypical male facial views was there any significant difference between professional and lay groups. For that view, a greater percentage of the layperson group preferred the narrow RED proportions. However, for the male dentofacial views that difference disappeared and both participant groups showed a slight preference for the broad proportion category. This may be due to the traditional esthetic stereotype for males to have broader, more vigorous appearing anterior teeth. For the prototypical female images, all participants expressed a clear, statistically significant preference for the narrower RED proportions in both full face and close up views. CONCLUSIONS: Based on the results above, dental professionals who are developing a treatment plan should attempt to utilize a RED proportion <= 0.70 for both male and female patients. CLINICAL SIGNIFICANCE: The RED proportion is an objective numeric tool for relating the apparent widths of maxillary anterior teeth. It may be used by dental professionals to help diagnose and develop an optimal esthetic treatment plan. This paper offers insight into whether there are specific RED proportions that are preferred, whether there is a difference in preference when considering the male or female smile and whether professional educational training changes those preferences. PMID- 26880427 TI - Phytochemistry and Pharmacological Activities of the Genus Gentiana (Gentianaceae). PMID- 26880428 TI - Contribution to a Taxonomic Revision of the Sicilian Helichrysum Taxa by PCA Analysis of Their Essential-Oil Compositions. AB - The chemical profile of the essential oils in ten populations of the genus Helichrysum Mill. (Asteraceae), collected in the loci classici of the nomenclatural types of the taxa endemic to Sicily, were analyzed. Our results confirm that the analysis of secondary metabolites can be used to fingerprint wild populations of Helichrysum, the chemical profiles being coherent with the systematic arrangement of the investigated populations in three main clusters, referring to the aggregates of H. stoechas, H. rupestre, and H. italicum, all belonging to the section Stoechadina. The correct nomenclatural designation of the investigated populations is discussed and the following two new combinations are proposed: Helichrysum preslianum subsp. compactum (Guss.) Maggio, Bruno, Guarino, Senatore & Ilardi and Helichrysum panormitanum subsp. latifolium Maggio, Bruno, Guarino, Senatore & Ilardi. PMID- 26880429 TI - Novel Nucleolipids of Pyrimidine beta-D-Ribonucleosides: Combinatorial Synthesis, Spectroscopic Characterization, and Cytostatic/Cytotoxic Activities. AB - Four series of nucleolipids with either uridine, 5-methyluridine, 5 fluorouridine, and 6-azauridine as beta-D-ribonucleoside component have been prepared in a combinatorial (not parallel!) manner (see Formulae). All compounds have been characterized by elemental analyses, ESI mass spectrometry as well as by (1) H-, and (13) C-NMR, and UV spectroscopy. A selection of eight nucleolipids with different lipophilizing moieties, based on earlier findings, as well as of 5 fluorouridine as control were first tested on their cytotoxic effect towards PMA differentiated human THP-1 macrophages. Those compounds which did not exhibit a significant inhibitory effect on the survival of the macrophages were next tested on their cytostatic/cytotoxic effect towards the human astrocytoma/oligodendroglioma GOS-3 cells as well as against the rat malignant neuroectodermal BT4Ca cell line. Additionally, induction of apoptosis of the cell lines was evaluated. It turned out that particularly a combined lipophilization of the nucleosides by an 2',3'-O-ethyl levulinate residue plus a farnesyl moiety at N(3) of the pyrimidine moiety of the corresponding nucleolipids leads to an active compound with the highest probability. PMID- 26880431 TI - New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina, a Forgotten Edible Alpine Plant. AB - Thirteen acylated flavonoid glycosides, 1-13, including eleven new congeners, 3 13, were isolated from the aerial parts of Pritzelago alpina (Brassicaceae) by a combination of column chromatography on Sephadex LH-20, and preparative and semi preparative HPLC. The structures were established by extensive NMR and MS experiments in combination with acid hydrolysis and sugar analysis by GC/MS. The new compounds were shown to be kaempferol and quercetin glycosides acylated for most of them by a branched short chain fatty acid or a hydroxycinnamic acid residue on the sugar portion. As shown by a HPLC-DAD analysis of a MeOH extract, these compounds are the main phenolic constituents in the aerial parts of the plant. PMID- 26880430 TI - Essential-Oil Variability in Natural Populations of Pinus mugo Turra from the Julian Alps. AB - The composition and variability of the terpenes and their derivatives isolated from the needles of a representative pool of 114 adult trees originating from four natural populations of dwarf mountain pine (Pinus mugo Turra) from the Julian Alps were investigated by GC-FID and GC/MS analyses. In total, 54 of the 57 detected essential-oil components were identified. Among the different compound classes present in the essential oils, the chief constituents belonged to the monoterpenes, comprising an average content of 79.67% of the total oil composition (74.80% of monoterpene hydrocarbons and 4.87% of oxygenated monoterpenes). Sesquiterpenes were present in smaller amounts (average content of 19.02%), out of which 16.39% were sesquiterpene hydrocarbons and 2.62% oxygenated sesquiterpenes. The most abundant components in the needle essential oils were the monoterpenes delta-car-3-ene, beta-phellandrene, alpha-pinene, beta-myrcene, and beta-pinene and the sesquiterpene beta-caryophyllene. From the total data set of 57 detected compounds, 40 were selected for principal-component analysis (PCA), discriminant analysis (DA), and cluster analysis (CA). The overlap tendency of the four populations suggested by PCA, was as well observed by DA. CA also demonstrated similarity among the populations, which was the highest between Populations I and II. PMID- 26880432 TI - Essential-Oil Constituents and Alkanes of Cephalaria ambrosioides Roem. & Schult. (Family Caprifoliaceae, Subfamily Dipsacaceae) and (Chemo)taxonomic Discernment of the Subfamilies Dipsacaceae and Morinaceae. AB - Herein, the results of the first study of the volatile and alkane profiles of Cephalaria ambrosioides Roem. & Schult. (Caprifoliaceae, subfamily Dipsacaceae) were reported. The GC-FID and GC/MS analyses of the essential oils hydrodistilled from leaves and stems (CA1) and flowers (CA2) of C. ambrosioides allowed the identification of 284 different components. The main compounds of the studied oil samples were palmitic acid (24.3 and 32.5% for CA1 and CA2, resp.), hexahydrofarnesyl acetone (1.4 and 10.8% for CA1 and CA2, resp.), (Z)-hex-3-en-1 ol (7.0 and <0.1% for CA1 and CA2, resp.), and linoleic acid (1.9 and 6.5% for CA1 and CA2, resp.). Essential-oil compositional data of selected plant species belonging to the Dipsacaceae (15) and Morinaceae (2) subfamilies were used to resolve taxonomical ambiguities regarding the genus Cephalaria and its infrageneric relations, especially concerning the subfamily Morinaceae (formerly a genus within Dipsacaceae). The results of multivariate statistical analyses (25 different essential-oil samples) supported the exclusion of Morina species from the Dipsacaceae subfamily. The relative abundances of alkanes from n-, iso-, and anteiso-series followed a (distorted) Gaussian-like distribution and suggested that the biosyntheses of n- and branched alkanes in C. ambrosioides are possibly not controlled by the same elongase. Also, the obtained results suggested that there was a difference in the biosynthesis/accumulation of alkanes in the vegetative and reproductive parts of C. ambrosioides. PMID- 26880433 TI - Comprehensive Study of Mediterranean (Croatian) Propolis Peculiarity: Headspace, Volatiles, Anti-Varroa-Treatment Residue, Phenolics, and Antioxidant Properties. AB - Eight propolis samples from Croatia were analyzed in detail, to study the headspace, volatiles, anti-Varroa-treatment residue, phenolics, and antioxidant properties. The samples exhibited high qualitative/quantitative variability of the chemical profiles, total phenolic content (1,589.3-14,398.3 mg GAE (gallic acid equivalent)/l EtOH extract), and antioxidant activity (11.1-133.5 mmol Fe(2+) /l extract and 6.2-65.3 mmol TEAC (Trolox(r) equivalent antioxidant capacity)/l extract). The main phenolics quantified by HPLC-DAD at 280 and 360 nm were vanillin, p-coumaric acid, ferulic acid, chrysin, galangin, and caffeic acid phenethyl ester. The major compounds identified by headspace solid-phase microextraction (HS-SPME), simultaneous distillation extraction (SDE), and subsequent GC-FID and GC/MS analyses were alpha-eudesmol (up to 19.9%), beta eudesmol (up to 12.6%), gamma-eudesmol (up to 10.5%), benzyl benzoate (up to 28.5%), and 4-vinyl-2-methoxyphenol (up to 18.1%). Vanillin was determined as minor constituent by SDE/GC-FID/MS and HPLC-DAD. The identified acaricide residue thymol was ca. three times more abundant by HS-SPME/GC-FID/MS than by SDE/GC FID/MS and was not detected by HPLC-DAD. PMID- 26880434 TI - Essential Oil Composition of Three Globularia Species. AB - The chemical composition of the essential oils obtained by hydrodistillation from the aerial parts of Globularia cordifolia L., G. meridionalis (Podp.) O.Schwarz, and G. punctata Lapeyr. was characterized by GC-FID and GC/MS analyses. Among the 33 identified compounds, the most abundant present in all investigated samples were oct-1-en-3-ol (2.9-47.0%), 6-(1,5-dimethylhex-4-enyl)-3-methylcyclohex-2 enone (8.2-40.9%), and fukinanolid (7.4-31.6%). Multivariate statistical analyses (PCA and HCA) of the hitherto studied Globularia volatile compounds confirmed to some extent the assumed phylogenetic relationships of the Globularia species studied, including the close relationship between the morphologically similar species G. cordifolia and G. meridionalis, but also evidenced several discrepancies in the current classification of Globularia species. PMID- 26880435 TI - 'Does my Diet Affect my Perfume?' Identification and Quantification of Cuticular Compounds in Five Drosophila melanogaster Strains Maintained over 300 Generations on Different Diets. AB - Cuticular hydrocarbons (CHCs) in Drosophila melanogaster represent the basis of chemical communication being involved in many important biological functions. The aim of this study was to characterize chemical composition and variation of cuticular profiles in five D. melanogaster strains. These strains were reared for approximately 300 generations on five diets: standard cornmeal medium and substrates prepared with apple, banana, tomato, and carrot. Differences in quantity and/or quality in CHCs were assumed as a result of activation of different metabolic pathways involved in food digestion and adaptations to the particular diet type. In total, independently of sex and strain, 66 chemical compounds were identified. In females of all strains, 60 compounds were identified, while, in males, 47 compounds were extracted. Certain new chemical compounds for D. melanogaster were found. MANOVA confirmed that CHC amounts significantly depend on sex and substrates, as well as on their interactions. Discriminant analysis revealed that flies belonging to 'apple' and 'carrot' strains exhibited the most noticeable differences in CHC repertoires. A non hydrocarbon pheromone, cis-vaccenyl acetate (cVA) also contributed to the variation in the pheromone bouquet among the strains. Variability detected in CHCs and cVA may be used in the explanation of differences in mating behaviour previously determined in analyzed fly strains. PMID- 26880437 TI - A Model of Information Carried over a Neuron Soma. AB - A series of cellular automata models of amino acid side chains on a neuron soma membrane have been created to simulate their hydropathic influences on adjacent water molecules. The presence of pathways, referred to as water wires, is identified. These pathways are invoked as passage ways across a neuron soma of proton hopping carrying the information from dendrites to the axon hillock. PMID- 26880436 TI - Characteristic Steroids from the South China Sea Gorgonian Muricella sibogae and Their Cytotoxicities. AB - Twenty-four steroid-based natural products, 9,10-secosteroids (1-10), 1,4-dien-3 one steroids (11-19), and 4-en-3-one steroids (20-24), containing varying side chains, were isolated from the South China Sea gorgonian Muricella sibogae. The structures of one new 9,10-secosteroid, sibogol D (1), and two new 1,4-dien-3-one steroids, sibogols E and F (11 and 12), were elucidated by extensive spectroscopic analyses and by comparison with the literature data. Cytotoxicities for all the isolates were evaluated against four selected tumor cell lines, HL 60, HCT116, K562, and P388. Compounds 3, 9, and 13 exhibited potent cytotoxic activities against the HL-60 cell line, with IC50 values ranging from 1.27 to 10.05 MUM, and compound 3 was also cytotoxic against HCT116 with an IC50 value of 5.8 MUM. The bioassay results also indicated a potential relationship between structural patterns and activity. The newly presented series of 1,4-dien-3-one and 4-en-3-one types of steroids relating to the unique 9,10-secosteroids in biogenesis were found in this species for the first time, which is of considerable chemotaxonomic significance. PMID- 26880438 TI - The Essential Oil Compositions of Ocimum basilicum from Three Different Regions: Nepal, Tajikistan, and Yemen. AB - The aerial parts of Ocimum basilicum L. were collected from four different geographical locations, Sindhuli and Biratnagar (Nepal), Chormaghzak village (Tajikistan), and Sana'a (Yemen). The essential oils were obtained by hydrodistillation and analyzed by gas chromatography/mass spectrometry. A cluster analysis of 179 essential oil compositions revealed six major chemotypes: Linalool, eugenol, estragole, methyl eugenol, 1,8-cineole, and geraniol. All four of the basil oils in this study were of the linalool-rich variety. Some of the basil oils were screened for bioactivity including antimicrobial, cytotoxicity in human cancer cells, brine shrimp lethality, nematicidal, larvicidal, insecticidal, and antioxidant. The basil oils in this study were not notably antibacterial, cytotoxic, antioxidant, nor nematicidal, but were active in the brine shrimp lethality test, and did show larvicidal and insecticidal activities. PMID- 26880439 TI - Sterols and Fatty Acids of the Harmful Dinoflagellate Cochlodinium polykrikoides. AB - Sterol and fatty acid compositions were determined for Cochlodinium polykrikoides, a toxic, bloom-forming dinoflagellate of global significance. The major sterols were dinosterol (40% of total sterols), dihydrodinosterol (32%), and the rare 4alpha-methyl Delta(8(14)) sterol, amphisterol (23%). A minor sterol, 4alpha-methylergost-24(28)-enol was also detected (5.0%). The fatty acids had a high proportion of PUFAs (47%), consisting mainly of EPA (20%) and the relatively uncommon octadecapentaenoic acid (18 : 5, 22%). While unlikely to be responsible for toxicity to fish, these lipids may contribute to the deleterious effects of this alga to invertebrates. PMID- 26880440 TI - Bioprospecting Chemical Diversity and Bioactivity in a Marine Derived Aspergillus terreus. AB - A comparative metabolomic study of a marine derived fungus (Aspergillus terreus) grown under various culture conditions is presented. The fungus was grown in eleven different culture conditions using solid agar, broth cultures, or grain based media (OSMAC). Multivariate analysis of LC/MS data from the organic extracts revealed drastic differences in the metabolic profiles and guided our subsequent isolation efforts. The compound 7-desmethylcitreoviridin was isolated and identified, and is fully described for the first time. In addition, 16 known fungal metabolites were also isolated and identified. All compounds were elucidated by detailed spectroscopic analysis and tested for antibacterial activities against five human pathogens and tested for cytotoxicity. This study demonstrates that LC/MS based multivariate analysis provides a simple yet powerful tool to analyze the metabolome of a single fungal strain grown under various conditions. This approach allows environmentally-induced changes in metabolite expression to be rapidly visualized, and uses these differences to guide the discovery of new bioactive molecules. PMID- 26880443 TI - We still go for the jugular: implications of the 3SITES central venous catheter study for nephrology. AB - The 3SITES study randomly assigned a nontunneled central venous catheter site in over 3000 adults treated in intensive care units. The subclavian site was associated with a lower rate of short-term complications, including catheter related bloodstream infection and deep venous thrombosis, compared to the femoral or internal jugular site. Nephrologists should be aware of this study and should continue to advocate for alternatives to subclavian vein catheter placement in patients with chronic kidney disease who are expected to require arteriovenous access for dialysis in the future. PMID- 26880442 TI - Averting the legacy of kidney disease--focus on childhood. AB - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplant, whereas only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID- 26880444 TI - Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis. AB - Inhibition of sodium-glucose cotransporter 2 causes both glycosuria and natriuresis, leading to reductions in hyperglycemia, body weight, blood pressure, and proteinuria. The recently published EMPA-REG OUTCOME study demonstrated significant cardiovascular and mortality benefits of sodium-glucose cotransporter 2 inhibition with empagliflozin in patients with type 2 diabetes and established cardiovascular disease, and may suggest a broader role for sodium-glucose cotransporter 2 inhibition in patients with heart failure. PMID- 26880445 TI - "AVOID"ing harm by a double-edged sword: is there a role for ultrafiltration in heart failure? AB - Prior studies comparing ultrafiltration with medical management for acute decompensated heart failure have yielded conflicting results. The AVOID-HF trial was designed as a definitive comparison of optimal ultrafiltration versus optimal diuretic-based medical therapy; unfortunately, the trial was terminated prematurely because of slow recruitment. The results of AVOID-HF nevertheless provide a rationale for well-designed, adequately powered trials to determine whether ultrafiltration has a role in the routine management of acute decompensated heart failure. PMID- 26880446 TI - Role of proton receptor OGR1 in bone response to metabolic acidosis? AB - Chronic metabolic acidosis stimulates bone resorption, resulting in loss of calcium and bicarbonate from bone. Both osteoblasts and osteoclasts sense extracellular H(+) by the G-protein coupled receptor, OGR1, whose activation leads to increased bone resorption as well as decreased bone formation. Krieger et al. examined the effect of OGR1 knockout in mice. They found an unexpected increase in bone resorption, but nevertheless an increase in bone volume linked to enhanced bone formation. This discovery opens a window of opportunity to explore potential new anabolic treatments for patients with low bone mass. PMID- 26880447 TI - The harmful effect of indoxyl sulfate on neovascularization in chronic kidney disease. AB - Patients with chronic kidney disease display an impairment of neovascularization in ischemic tissues. Studies have suggested the involvement of the uremic toxin indoxyl sulfate by demonstrating that indoxyl sulfate affects endothelial progenitor cells. However, few data are available on the effects of indoxyl sulfate on neovascularization and on the mechanisms involved. The article by Hung et al. shows that indoxyl sulfate suppresses neovascularization in uremic mice by impairing endothelial progenitor cell function via the inhibition of hypoxia induced hypoxia-inducible factor/interleukin-10/vascular endothelial growth factor signaling. PMID- 26880448 TI - Klotho connects intermedin1-53 to suppression of vascular calcification in chronic kidney disease. AB - Vascular calcification is one of the leading causes of death in chronic kidney disease (CKD) patients. Klotho protein encoded by the anti-aging gene, Klotho, and intermedin1-53 have both been shown to protect the vasculature from calcification in CKD. The study by Chang and colleagues links Klotho and intermedin1-53 in prevention of vascular calcification in CKD by showing that intermedin1-53 increased renal, vascular, and plasma Klotho, and reduced vascular calcification in CKD rats. Intermedin1-53 may be a novel therapeutic agent for CKD. PMID- 26880449 TI - Eculizumab in children with hemolytic uremic syndrome. AB - Greenbaum et al. report the first prospective trial of eculizumab in pediatric atypical hemolytic uremic syndrome. As in adult trials, eculizumab appears effective and no serious safety signals were reported. There is the first suggestion of a dichotomy in response to treatment with a trend toward poorer outcome in those without complement abnormalities. This group, however, had worse renal function at presentation, and it remains to be seen whether this represents true non-response or merely late presentation. PMID- 26880450 TI - The role of urinary peptidomics in kidney disease research. AB - Urinary peptidomics focuses on endogenous urinary peptide content. Many studies now show the usefulness of this approach for the discovery and validation of biomarkers in kidney diseases that are as varied as chronic kidney disease, acute kidney injury, congenital anomalies of the kidney and the urinary tract, and polycystic kidney disease. Most studies focus on chronic kidney disease and demonstrate that urinary peptidome analysis can substantially contribute to early detection and stratification of patients with chronic kidney disease. A number of multicenter studies are ongoing that aim further validation in a clinical setting and broaden the applicability of urinary peptides. The association of urinary peptides with kidney disease also starts to deliver information on the pathophysiology of kidney disease with emphasis on extracellular matrix remodeling. Bioinformatic peptide centric tools have been developed that allow to model the changes in protease activity involved in kidney disease, based on the urinary peptidome content. A novel application of urinary peptidome analysis is the back-translation of results obtained in humans to animals for animal model validation and improvement of readout in these preclinical models. In conclusion, urinary peptidomics not only contribute to detection and stratification of kidney disease in the clinic, but might also create a new impulse in drug discovery through better insight in the pathophysiology of disease and optimized translatability of animal models. PMID- 26880451 TI - Treatment of hyperkalemia: something old, something new. AB - Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin, sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals, Cary, NC), over 50 years ago. Although clinicians of that era did not have ready access to hemodialysis or loop diuretics, the other tools that we use today-calcium, insulin, and bicarbonate-were well known to them. Currently recommended insulin regimens provide too little insulin to achieve blood levels with a maximal kalemic effect and too little glucose to avoid hypoglycemia. Short acting insulins have theoretical advantages over regular insulin in patients with severe kidney disease. Although bicarbonate is no longer recommended for acute management, it may be useful in patients with metabolic acidosis or intact kidney function. Kayexalate is not effective as acute therapy, but a new randomized controlled trial suggests that it is effective when given more chronically. Gastrointestinal side effects and safety concerns about Kayexalate remain. New investigational potassium binders are likely to be approved in the coming year. Although there are some concerns about hypomagnesemia and positive calcium balance from patiromer, and sodium overload from ZS-9 (ZS Pharma, Coppell, TX), both agents have been shown to be effective and well tolerated when taken chronically. ZS-9 shows promise in the acute treatment of hyperkalemia and may make it possible to avoid or postpone the most effective therapy, emergency hemodialysis. PMID- 26880452 TI - Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. AB - Acute kidney injury (AKI) is a common complication in critically ill patients and subsequently worsens outcomes. Although many drugs to prevent and treat AKI have shown benefits in preclinical models, no specific agent has been shown to benefit AKI in humans. Moreover, despite remarkable advances in dialysis techniques that enable management of AKI in hemodynamically unstable patients with shock, dialysis-requiring severe AKI is still associated with an unacceptably high mortality rate. Thus, focusing only on kidney damage and loss of renal function has not been sufficient to improve outcomes of patients with AKI. Recent data from basic and clinical research have begun to elucidate complex organ interactions in AKI between kidney and distant organs, including heart, lung, spleen, brain, liver, and gut. This review serves to update the topic of organ cross talk in AKI and focuses on potential therapeutic targets to improve patient outcomes during AKI-associated multiple organ failure. PMID- 26880453 TI - Increased bone density in mice lacking the proton receptor OGR1. AB - Chronic metabolic acidosis stimulates cell-mediated calcium efflux from bone through osteoblastic prostaglandin E2-induced stimulation of receptor activator of NF-kB ligand leading to increased osteoclastic bone resorption. Osteoblasts express the proton-sensing G-protein-coupled receptor OGR1, which activates inositol phosphate-mediated intracellular calcium. Proton-induced osteoblastic intracellular calcium signaling requires ovarian cancer G-protein-coupled receptor 1 (OGR1), suggesting that OGR1 is the sensor activated during acidosis to cause bone resorption. Growing mice produce large amounts of metabolic acids, which must be buffered, primarily by bone, before excretion by the kidney. Here we tested whether lack of OGR1 inhibits proton-induced bone resorption by measuring bone mineral density by micro-computed tomography and histomorphometry in 8-week-old male OGR1(-/-) and C57/Bl6 wild type mice. OGR1(-/-) mice have normal skeletal development with no atypical gross phenotype. Trabecular and cortical bone volume was increased in tibiae and vertebrae from OGR1(-/-). There were increased osteoblast numbers on the cortical and trabecular surfaces of tibiae from OGR1(-/-) mice, increased endocortical and trabecular bone formation rates, and osteoblastic gene expression. Osteoclast numbers and surface were increased in tibiae of OGR1(-/-) mice. Thus, in rapidly growing mice, lack of OGR1 leads to increased bone mass with increased bone turnover and a greater increase in bone formation than resorption. This supports the important role of the proton receptor OGR1 in the response of bone to protons. PMID- 26880454 TI - Indoxyl sulfate suppresses endothelial progenitor cell-mediated neovascularization. AB - Patients with chronic kidney disease have an increased prevalence of peripheral arterial disease. Endothelial progenitor cells (EPC) are pivotal in neovascularization, but their role in mediating peripheral arterial disease in chronic kidney disease is not fully known. Here we studied the impact of indoxyl sulfate, a protein-bound uremic toxin, on EPC function in response to tissue ischemia or cell hypoxia in mice that underwent subtotal nephrectomy or sham operation. At 16 weeks, unilateral hindlimb ischemia was induced in all. Four weeks later, subtotal nephrectomy mice had significantly increased plasma levels of indoxyl sulfate, reduced reperfusion, decreased EPC mobilization, and impaired neovascularization in ischemic hindlimbs compared with control mice. Treatment with AST-120, an oral adsorbent of uremic toxins, reversed these changes. Ischemia-induced protein expression including phospho-eNOS, phospho-STAT3, interleukin-10, and VEGF were significantly decreased in ischemic hindlimbs of subtotal nephrectomy mice versus control mice; all effects were reversed by AST 120. Subtotal nephrectomy mice fed a diet with indole for 12 weeks resulted in impaired neovascularization in ischemic hindlimbs; also reversed by AST-120. In cultured human EPCs, VEGF expression was increased in hypoxia through HIF-1alpha and interleukin-10/STAT3 signaling; effects suppressed by pretreatment with indoxyl sulfate. Moreover, indoxyl sulfate markedly attenuated hypoxia-induced EPC migration and tube formation. Thus, indoxyl sulfate may be a therapeutic target for EPC-rescue of impaired neovascularization in patients with chronic kidney disease and peripheral arterial disease. PMID- 26880455 TI - Intermedin1-53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of alpha-Klotho. AB - Deficiency in alpha-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating alpha-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study. The aortas of rats with CKD showed reduced IMD content but an increase of its receptor, calcitonin receptor like receptor, and its receptor modifier, receptor activity-modifying protein 3. IMD1-53 treatment reduced vascular calcification. The expression of alpha-Klotho was greatly decreased in the aortas of rats with CKD but increased in the aortas of IMD1-53-treated rats with CKD. In vitro, IMD1-53 increased alpha-Klotho protein level in calcified vascular smooth muscle cells. alpha-Klotho knockdown blocked the inhibitory effect of IMD1-53 on vascular smooth muscle cell calcification and their transformation into osteoblast-like cells. The effect of IMD1-53 to upregulate alpha-Klotho and inhibit vascular smooth muscle cell calcification was abolished by knockdown of its receptor or its modifier protein, or treatment with the protein kinase A inhibitor H89. Thus, IMD1-53 may attenuate vascular calcification by upregulating alpha-Klotho via the calcitonin receptor/modifying protein complex and protein kinase A signaling. PMID- 26880456 TI - Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis. AB - Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract. PMID- 26880457 TI - The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL 17 dependent pathways during peritoneal dialysis. AB - Peritoneal dialysis (PD) can result in chronic inflammation and progressive peritoneal membrane damage. Alanyl-Glutamine (Ala-Gln), a dipeptide with immunomodulatory effects, improved resistance of mesothelial cells to PD fluids. Recently, interleukin-17 (IL-17) was found to be associated with PD-induced peritoneal damage. Here we studied the capacity of intraperitoneal Ala-Gln administration to protect against peritoneal damage by modulating IL-17 expression in uremic rat and mouse PD exposure models. Supplementation of PD fluid with Ala-Gln resulted in reduced peritoneal thickness, alphaSMA expression and angiogenesis. Addition of Ala-Gln also attenuated the IL-17 pathway expression induced by PD, reflected by substantial reduction or normalization of peritoneal levels of IL-17, transforming growth factor beta, IL-6, and the transcription factor retinoic acid receptor-related orphan receptor gamma T. Moreover, increased levels of IL-17 were associated with PD-induced peritoneal thickening. Conversely, Ala-Gln treatment prevented peritoneal extracellular matrix deposition, an effect seen with IL-17 blockade. Thus, intraperitoneal administration of Ala-Gln, a stable dipeptide commonly used in parenteral nutrition, ameliorates PD-induced peritoneal damage in animal models, in part by modulating IL-17 expression. Hence, Ala-Gln supplementation of dialysate may be a potential strategy to ameliorate peritoneal deterioration during PD. PMID- 26880458 TI - Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation. AB - Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10 to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09 1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study. PMID- 26880459 TI - Maternal compared with paternal donor kidneys are associated with poorer graft outcomes after kidney transplantation. AB - Noninherited maternal human leukocyte antigens may be less detrimental on allograft outcomes after kidney transplantation compared with noninherited paternal antigens, but this association in the era of modern immunosuppression remains unknown. Here we determine the association between parental donor kidneys, acute rejection, and graft failure in primary live-donor parental kidney transplant recipients using data from the Australia and New Zealand Dialysis and Transplant Registry between 1997 and 2012. Of the 1139 recipients followed for a median of 7.2 years (8588 person-years), 652 received kidneys from maternal donors. Compared with paternal donor kidneys, maternal donor kidneys were associated with a significantly increased risk of acute rejection (adjusted odds ratio 1.54; 95% confidence interval [CI], 1.14-2.07) and significant overall graft loss. The latter was confined to recipients who have experienced acute rejection (adjusted hazard ratio 1.60; 95%CI, 1.05-2.43) but not in those who did not experience acute rejection. Thus, our study suggests that recipients of maternal donor kidneys have a greater risk of rejection and graft loss. Hence, clinicians and patients should be cognizant of this association when determining which of the 2 parental donors is most suitable for transplantation. PMID- 26880460 TI - Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients. AB - Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24 month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52 11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality. PMID- 26880461 TI - Body mass index and causes of death in chronic kidney disease. AB - In chronic kidney disease (CKD), a higher body mass index (BMI) is associated with a lower risk for death, but cause-specific death details are unknown across the BMI range. To define this, we studied 54,506 patients with CKD (stage 3 CKD- [91.5%]) from an institutional electronic medical record based-registry. We examined the associations among various causes of death (cardiovascular-, malignancy- and noncardiovascular/nonmalignancy-related deaths) across the BMI range using Cox proportional hazards and competing risks regression models. During a median follow-up of 3.7 years, 14,518 patients died. In the multivariable model, an inverted J-shaped association was noted between BMI and cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy related deaths. Similar associations were noted for BMI 25-29.9, 30-34.9, and 35 39.9 kg/m(2) categories. A BMI >40 kg/m(2) was not associated with cardiovascular related and noncardiovascular/nonmalignancy-related deaths in CKD. Sensitivity analyses yielded similar results even after adjusting for proteinuria and excluding diabetes and hypertension from the models. In CKD, compared with a BMI of 18.5-24.9 kg/m(2), those who are overweight, with class 1 and 2 obesity have a lower risk for cardiovascular-related, malignancy-related, and noncardiovascular/nonmalignancy-related deaths. Future studies should examine the associations of other measures of adiposity with outcomes in CKD. PMID- 26880463 TI - Lung ultrasonography: a novel clinical tool to consider in nephrology. PMID- 26880462 TI - Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. AB - Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children. PMID- 26880464 TI - Ipilimumab-associated minimal-change disease. PMID- 26880465 TI - Absorbable phosphate in medication. PMID- 26880466 TI - Adriamycin susceptibility among C57BL/6 substrains. PMID- 26880467 TI - Toxoplasma chorioretinitis following renal transplantation. PMID- 26880468 TI - Myoglobinuric renal failure after a wasp attack. PMID- 26880469 TI - Make your diagnosis. The Case | Nonneurological tetraplegia. The Diagnosis | Alcohol-associated tubular dysfunction. PMID- 26880470 TI - Biodegradable Peptide-Silica Nanodonuts. AB - We report hybrid organosilica toroidal particles containing a short peptide sequence as the organic component of the hybrid systems. Once internalised in cancer cells, the presence of the peptide allows for interaction with peptidase enzymes, which attack the nanocarrier effectively triggering its structural breakdown. Moreover, these biodegradable nanovectors are characterised by high cellular uptake and exocytosis, showing great potential as biodegradable drug carriers. To demonstrate this feature, doxorubicin was employed and its delivery in HeLa cells investigated. PMID- 26880471 TI - Perioperative nutritional intervention: a way to improve long-term outcomes. PMID- 26880472 TI - Perioperative nutritional intervention: a way to improve long-term outcomes. PMID- 26880473 TI - Haematological cancer: Ibrutinib supercharges CAR T cells. PMID- 26880474 TI - Gastrointestinal cancer: CDX2: prognostic marker for high-risk colon cancer. PMID- 26880476 TI - Effectiveness of a universal internet-based prevention program for ecstasy and new psychoactive substances: a cluster randomized controlled trial. AB - AIM: To evaluate the effectiveness of an online school-based prevention program for ecstasy (MDMA) and new psychoactive substances (NPS). DESIGN: Cluster randomized controlled trial with two groups (intervention and control). SETTING: Eleven secondary schools in Australia. PARTICIPANTS: A total of 1126 students (mean age: 14.9 years). INTERVENTION: The internet-based Climate Schools: Ecstasy and Emerging Drugs module uses cartoon storylines to convey information about harmful drug use. It was delivered once weekly, during a 4-week period, during health education classes. Control schools received health education as usual. MEASUREMENT: Primary outcomes were self-reported intentions to use ecstasy and NPS at 12 months. Secondary outcomes were ecstasy and NPS knowledge and life-time use of ecstasy and NPS. Surveys were administered at baseline, post-intervention and 6 and 12 month post-baseline. FINDINGS: At 12 months, the proportion of students likely to use NPS was significantly greater in the control group (1.8%) than the intervention group [0.5%; odds ratio (OR) = 10.17, 95% confidence interval (CI) = 1.31-78.91]. However, students' intentions to use ecstasy did not differ significantly between groups (control = 2.1%, intervention = 1.6%; OR = 5.91, 95% CI = 1.01-34.73). There was a significant group difference in the change from baseline to post-test for NPS knowledge (beta = -0.42, 95% CI = -0.62 to -0.21, Cohen's d = 0.77), with controls [mean = 2.78, standard deviation (SD = 1.48] scoring lower than intervention students (mean = 3.85, SD = 1.49). There was also evidence of a significant group difference in ecstasy knowledge at post test (control: mean = 9.57, SD = 3.31; intervention: mean = 11.57, SD = 3.61; beta = -0.54, 95% CI = -0.97 to -0.12, P = 0.01, d = 0.73). CONCLUSIONS: The Climate Schools: Ecstasy and Emerging Drugs module, a universal online school based prevention program, appeared to reduce students' intentions to use new psychoactive substances and increased knowledge about ecstasy and new psychoactive substances in the short term. PMID- 26880475 TI - Impact of Awareness and Patterns of Nonhospitalized Atrial Fibrillation on the Risk of Mortality: The Reasons for Geographic And Racial Differences in Stroke (REGARDS) Study. AB - BACKGROUND: Although mortality associated with atrial fibrillation (AF) has been reported to decrease over prior decades, the mortality risk of asymptomatic, nonhospitalized AF has not been examined. HYPOTHESIS: Asymptomatic, nonhospitalized AF is associated with an increased risk of death. METHODS: This analysis included 25,976 participants (mean age, 65 +/- 9.4 years; 55% female; 38% black) from the Reasons for Geographic And Racial Differences (REGARDS) study. Atrial fibrillation was detected on the baseline electrocardiogram (ECG AF) or by self-reported history. Atrial fibrillation unawareness was defined as present if ECG evidence of the arrhythmia was detected but no self-reported history was reported. All-cause mortality was confirmed during follow-up through March 31, 2014. RESULTS: A total of 2208 (8.5%) participants had AF at baseline (ECG: n = 371/17%; self-reported: n = 1837/83%). Over a median follow-up of 7.6 years, 3481 deaths occurred. In a multivariable Cox regression model, AF was associated with a 32% increased risk of mortality (95% confidence interval [CI]: 1.19-1.46). Risk of death was higher among those with ECG AF (hazard ratio: 1.71, 95% CI: 1.42-2.07) compared with self-reported cases (hazard ratio: 1.15, 95% CI: 1.03-1.29). Those who were unaware of their AF diagnosis had a 94% increased risk of death (95% CI: 1.50-2.52) compared with AF participants who were aware of their diagnosis. CONCLUSIONS: Asymptomatic, nonhospitalized AF is associated with an increased risk of mortality in the general population. Mortality is higher in those with ECG-confirmed cases and among those who are unaware of their diagnosis. PMID- 26880477 TI - A New 1,3,4-Oxadiazole-Based Hole-Transport Material for Efficient CH3 NH3 PbBr3 Perovskite Solar Cells. AB - A new hole-transport material (HTM) based on the 1,3,4-oxadiazole moiety (H1) was prepared through a single-step synthetic pathway starting from commercially available products. Thanks to a deep HOMO level, H1 was used as HTM in CH3 NH3 PbBr3 perovskite solar cells yielding an efficiency of 5.8%. The reference HTM (Spiro-OMeTAD), under the same testing conditions, furnished a lower efficiency of 5.1%. Steady-state and time-resolved photoluminescence of the thin films showed good charge-extraction dynamics for H1 devices. In addition, H1 shows a large thermal stability and completely amorphous behavior (as evaluated by thermal gravimetric analysis and differential scanning calorimetry). PMID- 26880479 TI - Mimicking enzymatic systems: modulation of the performance of polymeric organocatalysts by ion-specific effects. AB - Like natural enzymatic systems, our study has demonstrated that the activity of the polymeric organocatalysts can be modulated by ion-specific effects via the combination of anion-specific salting-in/out effects and anion-specific polarization of hydrogen bonding induced stabilization of the transition state. PMID- 26880478 TI - Differential regulation of taurine biosynthesis in rainbow trout and Japanese flounder. AB - Animals have varied taurine biosynthesis capability, which was determined by activities of key enzymes including cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD). However, whether CDO and CSD are differentially regulated across species remains unexplored. In the present study, we examined the regulations of CDO and CSD in rainbow trout and Japanese flounder, the two fish species with high and low taurine biosynthesis ability respectively. Our results showed that the expression of CDO was lower in rainbow trout but more responsive to cysteine stimulation compared to that in Japanese flounder. On the other hand, both the expression and catalytic efficiency (k(cat)) of CSD were higher in rainbow trout than those of Japanese flounder. A three-residue substrate recognition motif in rainbow trout CSD with sequence of F126/S146/Y148 was identified to be responsible for high k(cat), while that with sequence of F88/N108/F110 in Japanese flounder led to low k(cat), as suggested by site directed mutagenesis studies. In summary, our results determined new aspects of taurine biosynthesis regulation across species. PMID- 26880480 TI - An association between systemic cyclosporine administration and development of acute bullous keratopathy in cats. AB - OBJECTIVE: To determine whether any association exists between the onset of feline acute bullous keratopathy (ABK) and administration of systemic corticosteroid or immunosuppressive therapy. ANIMALS STUDIED: Medical records of cats diagnosed with ABK between the years of 2000 and 2008 were retrospectively reviewed. Breed, age at diagnosis, weight, systemic disease status, eye affected, ophthalmic examination findings, systemic and topical therapy instituted, dosage and duration of therapy, visual outcome and histopathological analyses were recorded in cases meeting the inclusion criteria. RESULTS: A total of 12 cats of a surveyed population of 70 167 met the inclusion criteria with 17/24 eyes affected by ABK. Medical and/or surgical therapy was utilized for management of ABK with 13/17 eyes remaining sighted at the time of last follow-up. In a subset of cases corneal cytology, aerobic bacterial culture, FHV-1 PCR, virus isolation and/or histopathology were performed; no infectious organisms were identified. A rupture in Descemet's membrane of the cornea was identified histologically in two globes. A total of 10 of 12 cats had been previously diagnosed with ongoing systemic disease. A total of 10 of 12 cats were receiving systemic therapy, and a significant association (P < 0.001) was noted between systemic administration of corticosteroids and/or cyclosporine A and the development of ABK. A total of 8 of 10 cats were administered oral prednisolone at doses between 1-2 mg/kg every 12 24 h. A total of 5 of 8 cats receiving oral prednisolone were concurrently administered oral cyclosporine at doses of 1.5-7 mg/kg every 12-24 h. Systemic cyclosporine therapy was found to be a significant risk factor (P < 0.001) for ABK development, while systemic prednisolone was not significant (P = 0.10). CONCLUSIONS: Systemic cyclosporine administration appears to be a risk factor for development of ABK in the population of cats studied. PMID- 26880481 TI - Canine Staphylococcus pseudintermedius sinonasal infection in human hosts. AB - BACKGROUND: Staphylococcus pseudintermedius is a gram-positive bacterium commonly found as part of the normal skin and nasal flora of healthy dogs. It may act as an opportunistic pathogen in dogs, but has also been shown to colonize the nasal mucosa of humans. We report 4 cases of chronic rhinosinusitis (CRS) refractory to aggressive medical management with cultures that grew S. pseudintermedius, with clinical improvement only after initiating culture-directed therapy. METHODS: Retrospective review of 4 patients with CRS treated at a tertiary academic medical center with sinonasal cultures growing S. pseudintermedius. RESULTS: All 4 patients are dog owners and had clinical diagnoses of CRS. Three of the 4 patients had a diagnosis related to immune dysfunction (sarcoidosis, Crohn's disease, history of lymphoma). After undergoing endoscopic sinus surgery, each patient was treated with aggressive medical therapy but continued to have purulent nasal discharge. Sinonasal cultures repeatedly grew S. pseudintermedius in all cases, with 3 patients' dogs also having had concurrent S. pseudintermedius wound infections of the ear and leg with similar antibiotic susceptibilities. Treatment with culture-directed therapy improved the infections in all cases. CONCLUSION: Opportunistic pathogens have a propensity to exacerbate infection in CRS patients with immune dysfunction. We report the first case series of sinonasal S. pseudintermedius infection in humans. Though a rare cause of disease, pathogens such as S. pseudintermedius from nonhuman hosts should be considered in the management of CRS patients refractory to medical therapy. PMID- 26880482 TI - Complications of Hospital-Onset Healthcare Facility-Associated Clostridium difficile Infections Among Veterans. AB - Complications within 30 days of a clinically confirmed hospital-onset Clostridium difficile infection diagnosis from July 1, 2012, through June 30, 2015, in 127 acute care Veterans Health Administration facilities were evaluated. Pooled rates for attributable intensive care unit admissions, colectomies, and deaths were 2.7%, 0.5%, and 0.4%, respectively. Infect Control Hosp Epidemiol 2016;37:717 719. PMID- 26880483 TI - Trianguleniums as Optical Probes for G-Quadruplexes: A Photophysical, Electrochemical, and Computational Study. AB - Nucleic acids can adopt non-duplex topologies, such as G-quadruplexes in vitro. Yet it has been challenging to establish their existence and function in vivo due to a lack of suitable tools. Recently, we identified the triangulenium compound DAOTA-M2 as a unique fluorescence probe for such studies. This probe's emission lifetime is highly dependent on the topology of the DNA it interacts with opening up the possibility of carrying out live-cell imaging studies. Herein, we describe the origin of its fluorescence selectivity for G-quadruplexes. Cyclic voltammetry predicts that the appended morpholino groups can act as intra- molecular photo induced electron transfer (PET) quenchers. Photophysical studies show that a delicate balance between this effect and inter-molecular PET with nucleobases is key to the overall fluorescence enhancement observed upon nucleic acid binding. We utilised computational modelling to demonstrate a conformational dependence of intra-molecular PET. Finally, we performed orthogonal studies with a triangulenium compound, in which the morpholino groups were removed, and demonstrated that this change inverts triangulenium fluorescence selectivity from G-quadruplex to duplex DNA, thus highlighting the importance of fine tuning the molecular structure not only for target affinity, but also for fluorescence response. PMID- 26880484 TI - Poly C binding protein 1 represses autophagy through downregulation of LC3B to promote tumor cell apoptosis in starvation. AB - Accumulating evidences indicate that poly C binding protein (PCBP1) is downregulated in various carcinomas as a tumor suppressor, but the underlying mechanism in suppression of tumorigenesis still remains elusive. Here, we found that PCBP1 overexpression attenuates tumor cell growth upon serum-free starvation. Notably, the autophagic degradation inhibitor, chloroquine, could mimic this suppressive effect in tumor cell growth. Autophagy analyses demonstrated that PCBP1 overexpression blocked autophagic flux of tumor cells under starvation conditions, while PCBP1 downregulation in turn refueled this autophagic flux, protecting cells from death. Mechanistically, PCBP1 overexpression attenuated microtubule-associated protein Light chain 3 (LC3B) mRNA stability to repress LC3B expression, resulting in the autophagy inhibition. Consequently, PCBP1 overexpression strongly triggered the caspase 3 and 8 mediated apoptosis of tumor cells and downregulated anti-apoptotic Bcl-2 expression upon starvation, which could be further synergized by autophagic inhibitor, indicating that PCBP1 not only inhibits tumor cell autophagy, but also renders them to apoptosis. Taken together, our results uncovered a novel mechanism of PCBP1 in repressing autophagy-mediated cell survival and indicated that inhibition of tumor cell autophagy by PCBP1 upregulation or with autophagic inhibitors could be an effective therapeutical strategy to colon and ovary tumors with low PCBP1 expression. PMID- 26880486 TI - Cyclic Hypervalent Iodine Reagents for Atom-Transfer Reactions: Beyond Trifluoromethylation. AB - Hypervalent iodine compounds are privileged reagents in organic synthesis because of their exceptional reactivity. Among these compounds, cyclic derivatives stand apart because of their enhanced stability. They have been widely used as oxidants, but their potential for functional-group transfer has only begun to be investigated recently. The use of benziodoxol(on)es for trifluoromethylation (Togni's reagents) is already widely recognized, but other transformations have also attracted strong interest recently. In this Review, the development in the area since 2011 will be presented. After a short summary of synthetic methods to prepare benziodoxol(on)e reagents, their use to construct carbon-heteroatom and carbon-carbon bonds will be presented. In particular, the introduction of alkynes by using ethynylbenziodoxol(on)e (EBX) reagents has been highly successful. Breakthroughs in the introduction of alkoxy, azido, difluoromethyl, and cyano groups will also be described. PMID- 26880485 TI - Sex Biased Gene Expression Profiling of Human Brains at Major Developmental Stages. AB - There are many differences in brain structure and function between males and females. However, how these differences were manifested during development and maintained through adulthood are still unclear. Here we present a time series analyses of genome-wide transcription profiles of the human brain, and we identified genes showing sex biased expression at major developmental stages (prenatal time, early childhood, puberty time and adulthood). We observed a great number of genes (>2,000 genes) showing between-sex expression divergence at all developmental stages with the greatest number (4,164 genes) at puberty time. However, there are little overlap of sex-biased genes among the major developmental stages, an indication of dynamic expression regulation of the sex biased genes in the brain during development. Notably, the male biased genes are highly enriched for genes involved in neurological and psychiatric disorders like schizophrenia, bipolar disorder, Alzheimer's disease and autism, while no such pattern was seen for the female-biased genes, suggesting that the differences in brain disorder susceptibility between males and females are likely rooted from the sex-biased gene expression regulation during brain development. Collectively, these analyses reveal an important role of sex biased genes in brain development and neurodevelopmental disorders. PMID- 26880487 TI - "She Learned it from her Mother and Grandmother": Women's Experiences with Delivery and Post-partum Practices in Peri-urban Yangon, Myanmar. AB - BACKGROUND: Every year in Myanmar more than one million women give birth. Although births in hospitals and those attended by skilled birth attendants have increased considerably, the majority of women continue to give birth at home. Our needs assessment explored women's reproductive health in peri-urban Yangon, a rapidly growing area characterized by poor infrastructure, slum settlements and a mobile, migrant population. In this article, we focus specifically on the perceptions and experiences of adult women, key informants, and health care providers regarding delivery and post-partum care. METHODS: Our study team conducted a systematic literature review, 18 key informant interviews, 27 facility surveys, a survey with 147 adult women, and seven focus group discussions with women and health care providers over the summer of 2014. We analyzed these data for content and themes using deductive and inductive techniques and used descriptive statistics to analyze the survey results. RESULTS: Women in peri-urban Yangon are increasingly choosing to give birth in hospitals; however public hospitals are often inaccessible due to financial constraints and lack of transportation. Further, sociocultural and financial considerations continue to make deliveries with a traditional birth attendant an appealing option for some women and potentially harmful traditional post-partum practices remain common. CONCLUSIONS: Peri-urban populations face competing influences that guide decision-making surrounding delivery. Efforts to address the barriers to accessing hospital-based maternity services and trained providers appear warranted. The development of culturally-relevant resources that seek to raise awareness of the potential risks of traditional post-partum practices may also be of use. PMID- 26880488 TI - The Quadruple Bonding in C2 Reproduces the Properties of the Molecule. AB - Ever since Lewis depicted the triple bond for acetylene, triple bonding has been considered as the highest limit of multiple bonding for main elements. Here we show that C2 is bonded by a quadruple bond that can be distinctly characterized by valence-bond (VB) calculations. We demonstrate that the quadruply-bonded structure determines the key observables of the molecule, and accounts by itself for about 90% of the molecule's bond dissociation energy, and for its bond lengths and its force constant. The quadruply-bonded structure is made of two strong pi bonds, one strong sigma bond and a weaker fourth sigma-type bond, the bond strength of which is estimated as 17-21 kcal mol(-1). Alternative VB structures with double bonds; either two pi bonds or one pi bond and one sigma bond lie at 129.5 and 106.1 kcal mol(-1), respectively, above the quadruply bonded structure, and they collapse to the latter structure given freedom to improve their double bonding by dative sigma bonding. The usefulness of the quadruply-bonded model is underscored by "predicting" the properties of the (3)Sigma+u state. C2's very high reactivity is rooted in its fourth weak bond. Thus, carbon and first-row main elements are open to quadruple bonding! PMID- 26880489 TI - ID-Viewer: a visual analytics architecture for infectious diseases surveillance and response management in Pakistan. AB - OBJECTIVES: Globally, disease surveillance systems are playing a significant role in outbreak detection and response management of Infectious Diseases (IDs). However, in developing countries like Pakistan, epidemic outbreaks are difficult to detect due to scarcity of public health data and absence of automated surveillance systems. Our research is intended to formulate an integrated service oriented visual analytics architecture for ID surveillance, identify key constituents and set up a baseline for easy reproducibility of such systems in the future. STUDY DESIGN: This research focuses on development of ID-Viewer, which is a visual analytics decision support system for ID surveillance. It is a blend of intelligent approaches to make use of real-time streaming data from Emergency Departments (EDs) for early outbreak detection, health care resource allocation and epidemic response management. METHODS: We have developed a robust service-oriented visual analytics architecture for ID surveillance, which provides automated mechanisms for ID data acquisition, outbreak detection and epidemic response management. Classification of chief-complaints is accomplished using dynamic classification module, which employs neural networks and fuzzy logic to categorize syndromes. Standard routines by Center for Disease Control (CDC), i.e. c1-c3 (c1-mild, c2-medium and c3-ultra), and spatial scan statistics are employed for detection of temporal and spatio-temporal disease outbreaks respectively. Prediction of imminent disease threats is accomplished using support vector regression for early warnings and response planning. Geographical visual analytics displays are developed that allow interactive visualization of syndromic clusters, monitoring disease spread patterns, and identification of spatio-temporal risk zones. RESULTS: We analysed performance of surveillance framework using ID data for year 2011-2015. Dynamic syndromic classifier is able to classify chief-complaints to appropriate syndromes with high classification accuracy. Outbreak detection methods are able to detect the ID outbreaks in start of epidemic time zones. Prediction model is able to forecast dengue trend for 20 weeks ahead with nominal normalized root mean square error of 0.29. Interactive geo-spatiotemporal displays, i.e. heat-maps, and choropleth are shown in respective sections. CONCLUSION: The proposed framework will set a standard and provide necessary details for future implementation of such a system for resource constrained regions. It will improve early outbreak detection attributable to natural and man-made biological threats, monitor spatio-temporal epidemic trends and provide assurance that an outbreak has, or has not occurred. Advanced analytics features will be beneficial in timely organization/formulation of health management policies, disease control activities and efficient health care resource allocation. PMID- 26880490 TI - Mental health among currently enrolled medical students in Germany. AB - OBJECTIVES: The study identifies the prevalence of common mental disorders according to the patient health questionnaire (PHQ) and the use of psychotropic substances in a sample of currently enrolled medical students. STUDY DESIGN: A cross-sectional survey with a self-administrated questionnaire. METHODS: All newly enrolled medical students at the University of Dusseldorf, with study beginning either in 2012 or 2013, respectively, were invited to participate. The evaluation was based on 590 completed questionnaires. Mental health outcomes were measured by the PHQ, including major depression, other depressive symptoms (subthreshold depression), anxiety, panic disorders and psychosomatic complaints. Moreover, information about psychotropic substances use (including medication) was obtained. Multiple logistic regression analysis was used to estimate associations between sociodemographic and socio-economic factors and mental health outcomes. RESULTS: The prevalence rates, measured by the PHQ, were 4.7% for major depression, 5.8% for other depressive symptoms, 4.4% for anxiety, 1.9% for panic disorders, and 15.7% for psychosomatic complaints. These prevalence rates were higher than those reported in the general population, but lower than in medical students in the course of medical training. In all, 10.7% of the students reported regular psychotropic substance use: 5.1% of students used medication 'to calm down,' 4.6% 'to improve their sleep,' 4.4% 'to elevate mood,' and 3.1% 'to improve cognitive performance.' In the fully adjusted model, expected financial difficulties were significantly associated with poor mental health (odds ratio [OR]: 2.14; 95% confidence interval [CI]: 1.31-3.48), psychosomatic symptoms (OR:1.85; 95% CI: 1.11-3.09) and psychotropic substances use (OR: 2.68; 95% CI: 1.51-4.75). CONCLUSION: The high rates of mental disorders among currently enrolled medical students call for the promotion of mental health, with a special emphasis on vulnerable groups. PMID- 26880492 TI - India sets out plan to eliminate malaria by 2030. PMID- 26880491 TI - Lung ultrasound decreased radiation exposure in preterm infants in a neonatal intensive care unit. PMID- 26880494 TI - Bone-Prosthesis Junction for Active Tendon Implants: A Biomechanical Comparison of 2 Fixation Techniques. AB - PURPOSE: To study the biomechanical characteristics (percent stretch, stiffness, and ultimate load) of 2 distal fixation techniques for an active tendon implant used in the reconstruction of flexor tendons. METHODS: We evaluated percent stretch after cyclical loading and at failure, stiffness during load-to-failure, and peak load of 28 bone-prosthesis junctions using cadaveric canine middle phalanges to study 2 fixation techniques: metal cleat and screw versus polyester cords secured with a knot. RESULTS: The knot constructs displayed greater percent stretch during and following cyclical loading between 2 N and 50 N and at peak load. The screw construct showed greater stiffness from 50 N to 150 N during load to-failure. Both fixation techniques failed at a mean peak load greater than 340 N. CONCLUSIONS: Both fixation techniques for active tendon implants withstood loads seen with passive and active motion in the immediate postoperative period. Knot constructs displayed significant stretch during cyclical and load-to-failure testing, which would need to be compensated for during surgery. The screw constructs showed greater stiffness than the constructs secured with the surgeon's knot, but failure created an intra-articular fracture. CLINICAL RELEVANCE: The results may aid the surgeon in choosing which fixation technique to use, during tensioning of cords, and in permitting active motion following surgery. PMID- 26880493 TI - Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population. AB - This study aimed to assess the utility of transcription factor E3 (TFE3) break apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH positive group were 13.0 months (95% CI, 8.4-17.6 months) and 50.0 months (95% CI, 27.6-72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis. PMID- 26880495 TI - The Effect of Short Nerve Grafts in Series on Axonal Regeneration Across Isografts or Acellular Nerve Allografts. AB - PURPOSE: To evaluate the regenerative effect of the additional suture line when using either isografts (ISOs) or acellular nerve allografts (ANAs) placed end-to end to span a short gap in a rat model. METHODS: Rat sciatic nerves were transected and repaired with 2-cm nerve grafts (ISO or ANA). The grafts were 2 cm in length or a 1-cm segment was connected end-to-end to a 1-cm segment to yield a 2-cm length. At 8 weeks, extensor digitorum longus (EDL) muscle force and mass were measured. Nerves were harvested for histomorphometry. In a separate parallel study, the nerves were harvested 2 weeks following graft implantation to assess gene expression changes. RESULTS: All grafts demonstrated regeneration across the 2-cm segment(s). The additional suture line did not result in statistical differences in the number of myelinated nerve fibers that reached the distal nerve. However, when the graft types were compared, there was a significant decrease in nerve fibers in the ANA groups. The EDL muscle mass was significantly greater by using nerve ISOs compared with ANAs, regardless of an additional suture line, but there were no statistical differences noted in EDL muscle force. Gene expression analysis did not differ owing to an additional suture line. CONCLUSIONS: Minimal axonal loss and no functional deficits were identified with an additional suture line in this rodent short nerve gap model. CLINICAL RELEVANCE: Placing nerve grafts in series is a viable option for treating short nerve gaps; however, the use of autografts remains preferable over the use of ANAs. PMID- 26880496 TI - Health Literacy and Time Spent With a Hand Surgeon. AB - PURPOSE: To characterize the relationship between health literacy and duration of new hand surgery office visits. METHODS: Using a stopwatch from outside the room, we measured the duration of the visit (minutes of face-to-face contact between attending surgeon and patient) for 224 new patients presenting to 1 of 5 orthopedic hand surgeons (D.R.). Directly after the visit, patients were asked to complete the Newest Vital Sign (NVS) health literacy test, a sociodemographic survey, and 3 Patient-Reported Outcomes Measurement Information System-based questionnaires: Pain Interference, Upper Extremity Function, and Depression. The Newest Vital Sign scores were divided into limited (0-3) and adequate (4-6) health literacy. Medical records were reviewed to collect data on diagnosis, visit type, management, and whether patients were first seen by a resident/fellow. Multiple linear regression modeling was used to characterize the association between health literacy and duration of visit while controlling for the effect of other patient and visit characteristics. RESULTS: The unadjusted mean visit duration was 1.9 minutes shorter in patients with limited health literacy (9.4 minutes) than in patients with adequate health literacy (11.3 minutes), and this difference persisted after adjustment for a broad range of patient and visit characteristics. Greater magnitude of disability was associated with longer visits, as were second-opinion appointments, a diagnosis of nonspecific arm pain or compression neuropathy, and appointments in which operative management was chosen. Visits in which a resident/fellow saw the patient first were shorter than visits without resident/fellow assistance. CONCLUSIONS: The finding that limited health literacy correlated with shorter visits may suggest that patients who may stand to benefit the most from detailed health education and counseling received less. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. PMID- 26880497 TI - Care Transfers for Patients With Upper Extremity Trauma: Influence of Health Insurance Type. AB - PURPOSE: To understand the differences in transfer incidence for patients with upper extremity trauma by hospital trauma center designation. We hypothesized that patients with public or no insurance were more likely to be transferred to another facility compared with privately insured patients. METHODS: Trauma centers are designated by local authorities and verified by the American College of Surgeons. Using the 2012 National Trauma Data Bank, we examined the probability of being transferred from one center to another for patients who sustained isolated upper extremity trauma. We used multivariable logistic regression with a clustered variance method to adjust for intrahospital correlation to compare risk-adjusted transfer incidence for patients with upper extremity injuries by trauma center designation. RESULTS: In 2012, 6,214 patients ages 18-64 with isolated upper extremity trauma presented to 477 hospitals. Overall, transfer incidence was significantly higher among level III trauma centers (26%) compared with level II (11%) or level I (2%) trauma centers. Adjusting for patient and hospital characteristics patients with Medicaid were more likely to be transferred from level III trauma centers to another center compared with privately insured patients. CONCLUSIONS: Current regulations may not prevent unnecessary patient transfers based on insurance status among level III trauma centers. Policy makers should compensate or provide incentives to hospitals that take care of poorly insured patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/decision III. PMID- 26880498 TI - A Matched Comparative Study of the Bilhaut Procedure Versus Resection and Reconstruction for Treatment of Radial Polydactyly Types II and IV. AB - PURPOSE: To compare outcomes of the Bilhaut procedure with outcomes of conventional resection and reconstruction in radial polydactyly types II and IV. METHODS: Patients treated with the Bilhaut procedure were radiologically matched with patients treated with reconstruction. Evaluated outcomes included the Rotterdam assessment system, pinch strength, and thumb size measurements. To determine objectively which aesthetic outcome scores truly depended on surgical technique rather than observer opinion, we analyzed evaluations by a panel of 22 individuals with varying clinical experience who were blinded to the study protocol, using a linear mixed regression model. RESULTS: The Bilhaut procedure reduced the risk of suboptimal outcome for metacarpophalangeal joint instability in type IV radial polydactyly. Conversely, the Bilhaut procedure increased the risk of suboptimal scar appearance, residual prominence at amputation site, thumb size, and nail appearance. Tip pinch strength was more significantly reduced after the Bilhaut compared with reconstruction, whereas pulp circumference and nail width exceeded 100% of the unaffected contralateral hand after the Bilhaut reconstruction. There was no significant difference in active range of motion between procedures. Nail appearance proved the only aesthetic drawback of the Bilhaut procedure after adjustment for clinical experience. CONCLUSIONS: There was superior metacarpophalangeal joint stability after the Bilhaut procedure for radial polydactyly type IV, but this did not result in the presumed benefit to thumb strength. For experienced surgeons, both procedures resulted in comparable thumb active range of motion. However, aesthetic results were more likely perceived as pleasing after conventional reconstruction, even after adjusting for observer experience with regard to nail appearance. Despite possible benefits of modified Bilhaut procedures that preserve the nail, conventional reconstruction is the preferred procedure until otherwise proven. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III. PMID- 26880499 TI - A Comparison of Elbow Range of Motion Measurements: Smartphone-Based Digital Photography Versus Goniometric Measurements. AB - PURPOSE: The purpose of this study was to validate elbow flexion and extension measured from smartphone photography obtained by participants and compared them with photographs obtained by surgeons and goniometric measurements. METHODS: We enrolled 32 participants with a total of 64 elbows, aged 25 to 68 years. Participants obtained smartphone photographs of full elbow flexion and extension. Then surgeons obtained the same photographs and goniometric measurement of elbow range of motion (ROM). We measured ROM from the photographs using Adobe Photoshop and calculated average ROM. Comparisons of manual goniometer versus digital measurements, participant versus surgeon photograph measurements, and interobserver measurements were statistically analyzed. RESULTS: Average ROM measured by manual goniometer and digital photographs was 0 degrees to 129 degrees (range, 0 degrees to 140 degrees ) and 0 degrees to 129 degrees (range, 0 degrees to 145 degrees ), respectively. The goniometer versus digital measurements interclass correlation was 0.828 (L) and 0.740 (R). Pearson coefficient was 0.845 (L) and 0.757 (R). Bland-Altman plots demonstrated that 30 of 32 digital measurements (L) and 31 of 32 measurements (R) were within the 95% confidence interval. Participant-obtained photographs compared with researcher's photographs interclass correlation was 0.955 (L) and 0.941 (R), with a Pearson coefficient of 0.962 (L) and 0.957 (R), respectively. Reviewing interobserver reliability, concordance coefficients were 0.793 (L) and 0.767 (R) and Pearson coefficients were 0.811 (L) and 0.780 (R). Bland-Altman plots demonstrated that 28 of 32 digital measurements (L) and 26 of 32 measurements (R) were within the 95% confidence interval. CONCLUSIONS: Measuring elbow ROM using smartphone digital photography is valid and reliable. Participants were able to obtain accurate photographs and the measurements based on these photographs show no statistical difference from those taken by surgeons or goniometric measurement. CLINICAL RELEVANCE: This study validates using smartphone photography for measuring elbow ROM by laymen in a remote setting. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II. PMID- 26880500 TI - Generating trust: Programmatic strategies to reach women who inject drugs with harm reduction services in Dar es Salaam, Tanzania. AB - BACKGROUND: Strong evidence supports the effectiveness of methadone-assisted therapy (MAT) to treat opioid dependence, reduce the risk of HIV transmission, and improve HIV related health outcomes among people who inject drugs (PWID). HIV prevalence reaches 71% in women who inject drugs (WWID) in Dar es Salaam, Tanzania; creating an urgent need for access to MAT. Despite the availability and potential benefits of treatment, few women have enrolled in services. This formative research sought to identify programmatic strategies to increase women's participation in outreach and their subsequent enrollment in MAT. METHODS: We conducted twenty-five, in-depth interviews with patients and their providers at a MAT clinic. Open-ended interviews explored enrollment experiences, with a focus on contextual barriers and facilitators unique to women. Ethnographic observations of harm reduction education at outreach sites and the MAT clinic enriched interview data. Trust/mistrust emerged as an overarching theme cross cutting patient and provider accounts of the connective process to enroll PWID in the methadone program. We explore trust and mistrust in relationship to the interrelated themes of family loss, social isolation, vehement discrimination and motivation for treatment. RESULTS: Narratives delineated both the generation of mistrust against PWID and the generation of mistrust in PWID against outsiders and medical institutions. In order to enroll PWID in treatment, community base organizations engaged outreach strategies to overcome mistrust and connect eligible patients to care, which varied in their success at recruiting women and men. Greater discrimination against WWID pushed them into hiding, away from outreach teams that focus on outdoor areas where men who inject drugs congregate. Building trust through multiple encounters and making a personal connection facilitated entry into care for women. Only PWID were eligible for MAT, due to resource constraints and the higher risk associated with injection drug use. Many women smoke heroin, yet still face high risk of HIV, resulting from low condom use during sex work to fund drug use. CONCLUSION: Expanding outreach times and locations, by women peers, could increase women's enrollment in treatment. Allowing women who smoke heroin to enter the program could prevent onward transmission via sex work and reduce the chance of progressing from the lower risk smoking or sniffing to injection drug use. PMID- 26880501 TI - Novel 8-Hydroxyquinoline Derivatives as Multitarget Compounds for the Treatment of Alzheimer's Disease. AB - We discovered a small series of hit compounds that show multitargeting activities against key targets in Alzheimer's disease (AD). The compounds were designed by combining the structural features of the anti-AD drug donepezil with clioquinol, which is able to chelate redox-active metals, thus decreasing metal-driven oxidative phenomena and beta-amyloid (Abeta)-mediated neurotoxicity. The majority of the new hybrid compounds selectively target human butyrylcholinesterase at micromolar concentrations and effectively inhibit Abeta self-aggregation. In addition, compounds 5-chloro-7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8 hydroxyquinoline (1 b), 7-((4-(2-methoxybenzyl)piperazin-1-yl)methyl)-8 hydroxyquinoline (2 b), and 7-(((1-benzylpiperidin-4-yl)amino)methyl)-5-chloro-8 hydroxyquinoline (3 a) are able to chelate copper(II) and zinc(II) and exert antioxidant activity in vitro. Importantly, in the case of 2 b, the multitarget profile is accompanied by high predicted blood-brain barrier permeability, low cytotoxicity in T67 cells, and acceptable toxicity in HUVEC primary cells. PMID- 26880503 TI - Potential use of high levels of vegetal proteins in diets for market-sized gilthead sea bream (Sparus aurata). AB - The effect of partial or total dietary substitution of fishmeal (FM) by vegetal protein sources on growth and feed efficiency was carried out in on-growing gilthead sea bream (mean initial weight 131 g). The Control diet (FM 100) contained FM as the primary protein source, while in Diets FM 25 and FM 0 the FM protein was replaced at 75% and 100%, respectively, by a vegetable protein mixture consisting of wheat gluten, soybean meal, rapeseed meal and crystalline amino acids. Diets FM 25 and FM 0 also contained krill meal at 47 g/kg in order to improve palatability. At the end of the trial (after 158 d), fish survival was above 90%. Final weight and the specific growth rate were statistically lower in fish fed the Control diet (361 g and 0.64%/d), compared with 390-396 g and 0.69 0.70%/d after feeding vegetal diets. No significant differences were found regarding feed intake and feed conversion ratio. The digestibility of protein and amino acids (determined with chromium oxide as indicator) was similar in all diets. The blood parameters were not significantly affected by treatments. The activity of trypsin and pepsin was significantly reduced after feeding Diet FM 0. In the distal intestine, the villi length in fish fed Diet FM 25 was significantly longer and the intestine of the fish fed the FM 100 diet showed a smaller number of goblet cells. In conclusion, a total FM substitution by a vegetal mix supplemented with synthetic amino acids in on-growing sea bream is feasible. PMID- 26880502 TI - Pancreatic beta-Cell Membrane Fluidity and Toxicity Induced by Human Islet Amyloid Polypeptide Species. AB - Aggregation of human islet amyloid polypeptide (hIAPP) into fibrils and plaques is associated with pancreatic beta-cell loss in type 2 diabetes (T2D). However, due to the rapidness of hIAPP conversion in aqueous phase, exactly which hIAPP species is responsible for the observed toxicity and through what mechanisms remains ambiguous. In light of the importance of understanding hIAPP toxicity for T2D here we show a biophysical scheme based on the use of a lipophilic Laurdan dye for examining MIN6 cell membranes upon exposure to fresh and oligomeric hIAPP as well as mature amyloid. It has been found that all three hIAPP species, especially fresh hIAPP, enhanced membrane fluidity and caused losses in cell viability. The cell generation of reactive oxygen species (ROS), however, was the most pronounced with mature amyloid hIAPP. The correlation between changes in membrane fluidity and cell viability and their lack of correlation with ROS production suggest hIAPP toxicity is elicited through both physical and biochemical means. This study offers a new insight into beta-cell toxicity induced by controlled hIAPP species, as well as new biophysical methodologies that may prove beneficial for the studies of T2D as well as neurological disorders. PMID- 26880505 TI - Pelvic Organ Prolapse: New Concepts in Pelvic Floor Anatomy. AB - As the field of reconstructive pelvic surgery continues to evolve, with descriptions of new procedures to repair pelvic organ prolapse, it remains imperative to maintain a functional understanding of pelvic floor anatomy and support. The goal of this review was to provide a focused, conceptual approach to differentiating anatomic defects contributing to prolapse in the various compartments of the vagina. Rather than provide exhaustive descriptions of pelvic floor anatomy, basic pelvic floor anatomy is reviewed, new and historical concepts of pelvic floor support are discussed, and relevance to the surgical management of specific anatomic defects is addressed. PMID- 26880506 TI - Anatomy of the Vulva and the Female Sexual Response. AB - The female vulva is an intricate structure comprising several components. Each structure has been described separately, but the interplay among them and physiologic significance remain controversial. The structures extend inferiorly from the pubic arch and include the mons pubis, labia majora, labia minora, vestibule, and clitoris. The clitoris is widely accepted as the most critical anatomic structure to female sexual arousal and orgasm. The female sexual response cycle is also very complex, requiring emotional and mental stimulation in addition to end organ stimulation. PMID- 26880504 TI - The Epidemiology of Pelvic Floor Disorders and Childbirth: An Update. AB - Using a lifespan model, this article presents new scientific findings regarding risk factors for pelvic floor disorders (PFDs), focusing on the role of childbirth in the development of single or multiple coexisting PFDs. Phase I of the model includes predisposing factors, such as genetic predisposition and race. Phase II includes inciting factors, such as obstetric events. Prolapse, urinary incontinence (UI), and fecal incontinence (FI) are more common among vaginally parous women, although the impact of vaginal delivery on risk of FI is less dramatic than prolapse and UI. Phase III includes intervening factors, such as age and obesity. PMID- 26880507 TI - Stress Urinary Incontinence: Comparative Efficacy Trials. AB - Women seeking relief from symptoms of stress urinary incontinence (SUI) may choose from a broad array of treatment options. Therapies range from lifestyle/behavioral modification to surgical interventions, and differ in terms of both effectiveness and risk. Individualized treatment plans can be developed to address a patient's expectations and goals for treatment, as well as her tolerance for potential adverse events. This article reviews the highest-quality clinical trials comparing contemporary treatment options for women with SUI. Clinicians and patients can use this compendium to inform their treatment selection. PMID- 26880508 TI - Overactive Bladder. AB - Overactive bladder (OAB) is a condition affecting millions of individuals in the United States. Anticholinergics are the mainstay of treatment. Bladder botulinum toxin injections have shown an improvement in symptoms of OAB equivalent to anticholinergic therapy. Percutaneous tibial nerve stimulation can decrease symptoms of urinary frequency and urge incontinence. Sacral neuromodulation for refractory patients has been approved by the Food and Drug Administration for treatment of OAB, urge incontinence, and urinary retention. Few randomized, head to-head comparisons of the different available alternatives exist; however, patients now have increasing options to manage their symptoms and improve their quality of life. PMID- 26880509 TI - Native Tissue Prolapse Repairs: Comparative Effectiveness Trials. AB - This report reviews the success rates and complications of native tissue (nonmesh) vaginal reconstruction of pelvic organ prolapse by compartment. For apical prolapse, both uterosacral ligament suspensions and sacrospinous ligament fixations are effective and provided similar outcomes in anatomy and function with few adverse events. In the anterior compartment, traditional colporrhaphy technique is no different than ultralateral suturing. In the posterior compartment, transvaginal rectocele repair is superior to transanal repair. For uterine preservation, sacrospinous hysteropexy is not inferior to vaginal hysterectomy with uterosacral ligament suspension for treatment of apical uterovaginal prolapse. PMID- 26880510 TI - Pelvic Organ Prolapse---Vaginal and Laparoscopic Mesh: The Evidence. AB - This report summarizes the current literature on abdominal, laparoscopic, and transvaginal mesh for the treatment of pelvic organ prolapse. This article reviews objective and subjective cure rates as well as complications associated with synthetic mesh use for pelvic organ prolapse repair. The focus is on the latest literature that provides evidence for when synthetic mesh use is most appropriate. The use of mesh for the repair of urinary incontinence is not reviewed in this article. PMID- 26880512 TI - Registries as Tools for Clinical Excellence and the Development of the Pelvic Floor Disorders Registry. AB - Surgical device innovation has been less regulated than drug development, allowing integration of unproven techniques and materials into standard practice. Successful device registries gather information on patient outcomes and can provide postmarket surveillance of new technologies and allow comparison with currently established treatments or devices. The Pelvic Floor Disorders Registry was developed in collaboration with the Food and Drug Administration, device manufacturers, and other stakeholders to serve as a platform for industry sponsored postmarket device surveillance, investigator-initiated research, and quality and effectiveness benchmarking, all designed to improve the care of women with pelvic floor disorders. PMID- 26880513 TI - Informed Consent for Reconstructive Pelvic Surgery. AB - Informed consent is the process in which a patient makes a decision about a surgical procedure or medical intervention after adequate information is relayed by the physician and understood by the patient. This process is critical for reconstructive pelvic surgeries, particularly with the advent of vaginal mesh procedures. In this article, we review the principles of informed consent, the pros and cons of different approaches in reconstructive pelvic surgery, the current legal issues surrounding mesh use for vaginal surgery, and tips on how to incorporate this information when consenting patients for pelvic floor surgery. PMID- 26880514 TI - Ultrasound Imaging of the Pelvic Floor. AB - This article discusses the background and appraisal of endoluminal ultrasound of the pelvic floor. It provides a detailed anatomic assessment of the muscles and surrounding organs of the pelvic floor. Different anatomic variability and pathology, such as prolapse, fecal incontinence, urinary incontinence, vaginal wall cysts, synthetic implanted material, and pelvic pain, are easily assessed with endoluminal vaginal ultrasound. With pelvic organ prolapse in particular, not only is the prolapse itself seen but the underlying cause related to the anatomic and functional abnormalities of the pelvic floor muscle structures are also visualized. PMID- 26880511 TI - Evidence-Based Update on Treatments of Fecal Incontinence in Women. AB - Fecal incontinence is a highly prevalent and distressing condition that has a negative impact on quality of life. The etiology is often multifactorial, and the evaluation and treatment of this condition can be hindered by a lack of understanding of the mechanisms and currently available treatment options. This article reviews the evidence-based update for the management of fecal incontinence. PMID- 26880515 TI - Keeping Informed About Management Options for Pelvic Floor Disorders. PMID- 26880516 TI - Medical and Advanced Surgical Management of Pelvic Floor Disorders. PMID- 26880517 TI - See the unseen: Mesorectal lymph node metastases in prostate cancer. AB - BACKGROUND: Our study is the first evaluation of nodal metastatic prostate cancer (PCa) to mesorectal lymph nodes (MLN) detected by (68) Ga-PSMA-PET/CT. METHODS: We retrospectively analyzed 76 consecutive PCa patients who underwent (68) Ga PSMA-PET/CT: 61 PCa patients with biochemical recurrence (BCR) after curative treatment and 15 high-risk PCa before primary therapy. We assessed PET-positive MLN, which are indicative for PCa. RESULTS: We detected PET-positive lesions for PCa in (68) Ga-PSMA-PET/CT in 66 of 76 (87%) patients. Nodal disease was imaged in 47 of 66 (71%) patients. Indicative mesorectal nodal lesions for PCa were detected in 12 of 76 (15.8%) patients. The median number of PET-positive MLN was one per patient. Seven of twelve patients had recurrent PCa after radical prostatectomy with a median PSA value of 1.84 ng/ml (range 0.31-13). Five of twelve patients had untreated first diagnosed high-risk PCa with median PSA value of 90 ng/ml (range 4.6-93) at PET/CT, respectively. For all PET positive MLN a morphological correlate was found in CT (shortest diameter median 4 mm [range 4 21]; longest diameter median 7.5 mm [range 5-25]). After PET/CT, four patients with recurrent PCa received hormonal therapy, one patient was treated with directed radiation therapy of MLN, one patient received chemotherapy, and one patient was treated with pelvic lymph node dissection. Three high-risk PCa patients received hormonal therapy, and two patients were treated with adjuvant hormonal therapy after radical prostatectomy. CONCLUSIONS: Detection and exact location of nodal metastasis for PCa is crucial for the choice of treatment and the patient's prognosis. (68) Ga-PSMA-PET/CT seems to improve the detection of nodal metastasis in PCa, especially concerning mesorectal lymph nodes. PMID- 26880518 TI - Highly energetic compositions based on functionalized carbon nanomaterials. AB - In recent years, research in the field of carbon nanomaterials (CNMs), such as fullerenes, expanded graphite (EG), carbon nanotubes (CNTs), graphene, and graphene oxide (GO), has been widely used in energy storage, electronics, catalysts, and biomaterials, as well as medical applications. Regarding energy storage, one of the most important research directions is the development of CNMs as carriers of energetic components by coating or encapsulation, thus forming safer advanced nanostructures with better performances. Moreover, some CNMs can also be functionalized to become energetic additives. This review article covers updated preparation methods for the aforementioned CNMs, with a more specific orientation towards the use of these nanomaterials in energetic compositions. The effects of these functionalized CNMs on thermal decomposition, ignition, combustion and the reactivity properties of energetic compositions are significant and are discussed in detail. It has been shown that the use of functionalized CNMs in energetic compositions greatly improves their combustion performances, thermal stability and sensitivity. In particular, functionalized fullerenes, CNTs and GO are the most appropriate candidate components in nanothermites, solid propellants and gas generators, due to their superior catalytic properties as well as facile preparation methods. PMID- 26880519 TI - Semi-volatile organic compounds in the air and dust of 30 French schools: a pilot study. AB - The contamination of indoor environments with chemical compounds released by materials and furniture, such as semi-volatile organic compounds (SVOCs), is less documented in schools than in dwellings-yet children spend 16% of their time in schools, where they can also be exposed. This study is one of the first to describe the contamination of the air and dust of 90 classrooms from 30 nursery and primary schools by 55 SVOCs, including pesticides, phosphoric esters, musks, polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs), phthalates, and polybromodiphenylethers (PBDEs). Air samples were collected using an active sampling method, and dust samples were collected via two sampling methods (wiping and vacuum cleaning). In air, the highest concentrations (median >100 ng/m3 ) were measured for diisobutyl phthalate (DiBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), bis(2-ethylhexyl) phthalate (DEHP), and galaxolide. In dust, the highest concentrations (median >30 MUg/g) were found for DEHP, diisononyl phthalate (DiNP), DiBP, and DBP. An attempt to compare two floor dust sampling methods using a single unit (ng/m2) was carried out. SVOC concentrations were higher in wiped dust, but frequencies of quantification were greater in vacuumed dust. PMID- 26880520 TI - Staging significance of bone invasion in small-sized (4cm or less) oral squamous cell carcinoma as defined by the American Joint Committee on Cancer. AB - OBJECTIVES: The staging significance of bone invasion is controversial in oral squamous cell carcinoma (OSCC) cases with tumors measuring 4cm or less according to the American Joint Committee on Cancer (AJCC). Our aim was to retrospectively examine a large group of patients with OSCC to determine the staging significance of bone invasion. MATERIALS AND METHODS: Three hundred and twenty-three patients with primary OSCC were classified based on tumor size. Bone invasion was categorized as absent, one side bone, and both buccal and lingual bones, and analyzed for association with disease progression. Regional lymph node metastasis (N), perineural invasion, vascular invasion, surgical margin involvement, and adjuvant treatment were also analyzed. RESULTS: In all OSCC cases, bone invasion (p=0.007) with stage N, perineural invasion, and surgical margin involvement were significant independent prognostic factors of disease progression. However, in OSCC cases with tumors measuring 4cm or less, bone invasion was not significantly associated with disease progression. Nevertheless, invasion of both buccal and lingual bones was significantly associated with disease progression (p=0.03). In multivariate analysis, both buccal and lingual bone invasion (p=0.04; hazard ratio=3.4; 95% confidence interval, 1.0-11.0), stage N2, and perineural invasion were also independent prognostic factors. CONCLUSION: Although OSCC bone invasion was an independent prognostic factor, bone invasion in small OSCC was not. However, small OSCC with both buccal and lingual bone invasion had a significantly worse prognosis. The AJCC T system is of limited prognostic value for small OSCC with bone invasion. But other elements should be examined before a modification can be accepted. PMID- 26880521 TI - Characterization of persistent colors and decolorization of effluent from biologically treated cellulosic ethanol production wastewater. AB - The high chroma of cellulosic ethanol production wastewater poses a serious environmental concern; however, color-causing compounds are still not fully clear. The characteristics of the color compounds and decolorization of biologically treated effluent by electro-catalytic oxidation were investigated in this study. Excitation-emission matrix (EEM), fourier transform infrared spectrometer (FTIR), UV-Vis spectra, and ultrafiltration (UF) fractionation were used to analyze color compounds. High chroma of wastewater largely comes from humic materials, which exhibited great fluorescence proportion (67.1 %) in the biologically treated effluent. Additionally, the color compounds were mainly distributed in the molecular weight fractions with 3-10 and 10-30 kDa, which contributed 53.5 and 34.6 % of the wastewater color, respectively. Further decolorization of biologically treated effluent by electro-catalytic oxidation was investigated, and 98.3 % of color removal accompanied with 97.3 % reduction of humic acid-like matter was achieved after 180 min. The results presented herein will facilitate the development of a well decolorization for cellulosic ethanol production wastewater and better understanding of the biological fermentation. PMID- 26880522 TI - Catalyst support materials for prominent mineralization of bisphenol A in catalytic ozonation process. AB - Degradation of aqueous solution of bisphenol A (BPA) has been investigated through non-catalytic and catalytic ozonation treatments conducted in a semi batch reactor. Non-catalytic ozonation resulted in complete degradation of aqueous BPA in less than 3 min but did not completely convert the reaction intermediates of BPA ozonation into CO2 and H2O. The main goal of this study was to find an effective heterogeneous catalyst to increase the extent of BPA mineralization at different pH conditions. In this way, the most promising catalyst carrier was gamma-Al2O3; at pH = 8.0, 68 % of total organic carbon (TOC) was removed in the period of 75 min, out of which 42 % was attributed to mineralization. Finally, 3.0 wt.% Ru/gamma-Al2O3 catalyst exhibited over 82 % of TOC removal after 240 min of ozonation at pH = 5.9, of which 56 % was mineralized. PMID- 26880524 TI - An ecological vegetation-activated sludge process (V-ASP) for decentralized wastewater treatment: system development, treatment performance, and mathematical modeling. AB - An environment-friendly decentralized wastewater treatment process that is comprised of activated sludge process (ASP) and wetland vegetation, named as vegetation-activated sludge process (V-ASP), was developed for decentralized wastewater treatment. The long-term experimental results evidenced that the vegetation sequencing batch reactor (V-SBR) process had consistently stable higher removal efficiencies of organic substances and nutrients from domestic wastewater compared with traditional sequencing batch reactor (SBR). The vegetation allocated into V-SBR system could not only remove nutrients through its vegetation transpiration ratio but also provide great surface area for microorganism activity enhancement. This high vegetation transpiration ratio enhanced nutrients removal effectiveness from wastewater mainly by flux enhancement, oxygen and substrate transportation acceleration, and vegetation respiration stimulation. A mathematical model based on ASM2d was successfully established by involving the specific function of vegetation to simulate system performance. The simulation results on the influence of operational parameters on V-ASP treatment effectiveness demonstrated that V-SBR had a high resistance to seasonal temperature fluctuations and influent loading shocking. PMID- 26880525 TI - An evaluation of factors affecting preference for immediate, delayed or no breast reconstruction in women with high-risk breast cancer. AB - OBJECTIVE: Women with locally advanced breast cancer face many conflicting issues affecting their choice of immediate versus delayed versus no breast reconstruction (BR). This single-centre pilot study assessed high-risk women's reasons and priorities in choosing the timing and type of BR in a setting where all clinically feasible options were discussed with all women. METHODS: Fifty-one women from a metropolitan breast oncology practice, who were likely to require post-mastectomy radiotherapy (PMRT), were recruited after making their decision about BR. Participants completed a questionnaire (69% preoperatively), adapted from Reaby (1998), evaluating the factors affecting their decision. Responses were subsequently classified into eight issue-based domains (feeling normal, feeling good, being practical, influence of others, expectations, fear, timing and unnecessary). Demographic and clinical data were also collected. RESULTS: There were 32 immediate BR (IBR = 63%), seven delayed BR (DBR = 13%) and 12 no BR (NBR = 23%). Analysis using the chi square test showed women over 60 were more likely to choose NBR (p = 0.005), while women living with a partner were more likely to choose IBR (p = 0.032). The most relevant domains for both IBR and DBR were 'feeling good' and 'feeling normal'; and for NBR were 'unnecessary' and 'being practical'. Although all women understood pre-operatively the potential aesthetic limitations of PMRT, 63% still chose IBR. CONCLUSIONS: These data will enable clinicians, researchers and women with breast cancer to gain a clearer understanding of the factors that impact on the choice and timing of BR in women requiring PMRT, a major breast cancer survivorship decision. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26880523 TI - Relationship between e-waste recycling and human health risk in India: a critical review. AB - Informal recycling of waste (including e-waste) is an emerging source of environmental pollution in India. Polychlorinated biphenyls (PCBs), polychlorinated diphenyl ethers (PBDEs), and heavy metals, among other substances, are a major health concern for workers engaged in waste disposal and processing, and for residents living near these facilities, and are also a detriment to the natural environment. The main objective of this review article was to evaluate the status of these impacts. The review found that, huge quantity of e-waste/waste generated, only a small amount is treated formally; the remainder is processed through the informal sector. We also evaluated the exposure pathways, both direct and indirect, and the human body load markers (e.g., serum, blood, breast milk, urine, and hair), and assessed the evidence for the association between these markers and e-waste exposure. Our results indicated that the open dumping and informal e-waste recycling systems should be replaced by the best available technology and environmental practices, with proper monitoring and regular awareness programs for workers and residents. Further and more detailed investigation in this area is also recommended. PMID- 26880526 TI - Development of a patient decision aid for the treatment of localised prostate cancer: a participatory design approach. AB - AIMS AND OBJECTIVES: To develop a patient decision aid and to prepare an overview of requirements for implementation. BACKGROUND: We developed a decision aid that fits the preferences of patients and health care professionals to ensure adequate uptake in clinical practice. DESIGN: A participatory design approach was used to acquire insight into preferences regarding the content and design of a decision aid and into barriers and aspects of the decision aid that facilitate implementation in clinical practice. METHODS: Three focus group interviews with patients, their partners and health care professionals were conducted. A prototype of the decision aid was developed and presented to patients (n = 14) and health care professionals (n = 13) in semi-structured interviews. Patients (n = 5) participated in a usability study. Data were analysed by two independent coders. RESULTS: Health care professionals considered medical information on treatments and side effects as the most important aspect to be included in the decision aid. Patients also focused on nonmedical considerations, such as location. Both expected the decision aid to support patients in making a treatment choice. According to health care professionals, the oncology nurse was the most suitable to discuss the decision aid with patients, while some patients preferred to discuss the patient decision aid with the urologist. The main barrier to implementation of the decision aid was said to be the expectation that it is time and money consuming, while the incorporation of the decision aid into clinical guidelines and basing the content on these guidelines, would promote implementation. CONCLUSIONS: By using a participatory design approach a patient decision aid was designed to meet patients' and health care professionals' needs. Insight was also gained on requirements for implementation. RELEVANCE TO CLINICAL PRACTICE: Wide-scale implementation of decision aids is desirable. An overview is provided of requirements for implementation to successfully incorporate a decision aid into clinical practice. PMID- 26880527 TI - Methods for Quantifying the Clinical Significance of Change During Intervention Program Participation. AB - Assessing the practical or clinical significance (CS) of an intervention program's outcomes is useful in determining its effectiveness. The CS approach gives information beyond traditional analyses by quantifying the proportions of people who meaningfully improve and deteriorate. We link latent transition analyses (LTA) to the CS literature and use a case study to contrast it with the long-standing Jacobson and Truax (JT) approach. Data came from 2,717 individuals convicted of a substance-related offense who participated in an indicated prevention program Prime For Life(r) (PFL). We selected outcomes describing drinking beliefs and behavior. Both CS approaches categorized a majority of participants as improved (i.e., transitioning from baseline subgroups with risky behaviors and cognitions into posttest subgroups showing lower risk). Results demonstrate how the JT approach allows the assessment of improvements on individual outcomes, while the LTA provides more nuanced information about risk groupings. Selecting a CS approach depends on research goals, availability of normative data, and data considerations. JT is an appropriate method when evaluating single outcomes. In contrast, LTA is better when a multivariate description is desired, advanced missing data handling methods are needed, or outcomes are not normally distributed. Although infrequently done, evaluating CS provides useful information about program effectiveness. PMID- 26880528 TI - Hemifacial Spasm in a Child Treated With Microvascular Decompression of the Facial Nerve. AB - BACKGROUND: Hemifacial spasm is a rare condition in children that is characterized by involuntary contractions of muscles innervated by the ipsilateral facial nerve. PATIENT DESCRIPTION: We describe a 6-year-old girl who presented with intermittent involuntary spasms of the right face. Magnetic resonance imaging demostrated a loop of the anterior inferior cerebral artery contacting and elevating the cisternal segment of the right facial nerve; this finding was confirmed at surgery where microvascular decompression of the facial nerve was performed without complication. Following surgery she had immediate remission of symptoms, but the hemifacial spasms slowly recurred within 8 months of surgery only to resolve by age 11 years. CONCLUSION: This is the youngest patient reported with hemifacial spasms related to a vascular etiology, which initially responded to surgical treatment. The authors review this syndrome in children and discuss possible etiologies and management options. PMID- 26880529 TI - Ictal Coprolalia: A Case Report and Review of Ictal Speech as a Localizing Feature in Epilepsy. AB - BACKGROUND: Recognizing ictal semiology is an essential component to localization of seizure onset, especially in intractable epilepsy where surgical therapies may be beneficial. Ictal speech can be a common component of seizure semiology, but the various forms of ictal speech may have different lateralizing and localizing value. Coprolalia is a very rare form of ictal speech. METHODS: We present a 15 year old with medically intractable seizures characterized by agitation and coprolalia. RESULTS: The patient underwent surgical evaluation including video EEG, MRI, and functional neuroimaging. These studies indicated onset within the dominant frontal lobe which was further localized using stereo electroencephalography prior to focal cortical resection. CONCLUSIONS: Ictal coprolalia is a rare presentation of ictal speech. We review the various forms of ictal speech and their value in localizing seizure onset. PMID- 26880530 TI - The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults. AB - KEY POINTS: A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship. This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP. We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP. Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP. Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. ABSTRACT: The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 +/- 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8 10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min(-1) (Light) and 120 beats min(-1) (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 +/- 0.08 to 0.25 +/- 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP (r(2) = 0.26, P < 0.001). Changes in PASP (r(2) = 0.43, P < 0.001), PADP (r(2) = 0.47, P < 0.001) and mPAP (r(2) = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP. PMID- 26880531 TI - Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats. AB - OBJECTIVE: We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection. DESIGN: One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs. RESULTS: Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one. CONCLUSION: Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors. PMID- 26880532 TI - Tailored Cyclic and Linear Polycarbosilazanes by Barium-Catalyzed N-H/H-Si Dehydrocoupling Reactions. AB - Ba[CH(SiMe3 )2 ]2 (THF)3 catalyzes the fast and controlled dehydrogenative polymerization of Ph2 SiH2 and p-xylylenediamine to afford polycarbosilazanes. The structure (cyclic versus linear; end-groups) and molecular weight of the macromolecules can be tuned by adjusting the Ph2 SiH2 /diamine feed ratio. A detailed analysis of the resulting materials (mol. wt up to ca. 10 000 g mol(-1) ) is provided. PMID- 26880533 TI - The interrelationships of birthweight, inflammation and body composition in healthy adults. AB - BACKGROUND: Lower birthweight is associated with an increased risk of cardiovascular diseases and diabetes. We hypothesized that inflammation and body fat may be potential mediators for these inverse relationships. MATERIALS AND METHODS: Healthy adults aged 25-41 years were enrolled in a prospective population-based cohort study in the Principality of Liechtenstein. Main exclusion criteria were diabetes, overt cardiovascular disease or a body mass index > 35 kg/m(2) . Birthweight was self-reported by the study participants. White blood cell (WBC) count and high-sensitivity C-reactive protein (hs-CRP) levels were assayed from fresh blood samples. Body composition was determined by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships between birthweight, inflammation and body composition. RESULTS: Our sample consisted of 1774 participants (53.4% females) with a median age of 37 years. Median birthweight was 3355 g. In multivariable models, we found an inverse relationship of birthweight with hs-CRP levels (beta -0.010 (95% CI -0.02; -0.002), P = 0.01) and WBC count (beta -0.002 (95% CI -0.004; -0.0002), P = 0.03). Additional adjustment for body fat mass attenuated these relationships (beta -0.008 (95% CI -0.02; 0.0003), P = 0.06 for hs-CRP levels and (beta -0.002 (95% CI -0.004; 0.0006), P = 0.16 for WBC count. Body fat mass itself was strongly associated with birthweight (beta -0.06 (95% CI -0.10; -0.03), P < 0.0001). CONCLUSION: Birthweight is inversely associated with inflammation in adulthood. This relationship may be mediated by an elevated body fat mass among individuals with lower birthweight. PMID- 26880534 TI - GPER is required for the age-dependent upregulation of the myocardial endothelin system. AB - AIMS: Cardiac aging is associated with progressive structural changes and functional impairment, such as left ventricular hypertrophy, fibrosis and diastolic dysfunction. Aging also increases myocardial activity of endothelin-1 (ET-1), a multifunctional peptide with growth-promoting and pro-fibrotic activity. Because the G protein-coupled estrogen receptor (GPER) regulates vascular responsiveness to ET-1, we investigated whether GPER also plays a role in the regulation of the myocardial endothelin system with aging. MAIN METHODS: Young (4month-old) and aged (24month-old) wild-type and Gper-deficient (Gper(-/ )) mice were studied. Gene expression levels of prepro-ET-1, endothelin converting enzymes ECE-1 and ECE-2, and endothelin ETA and ETB receptors were determined by qPCR in left ventricular myocardium. KEY FINDINGS: Aging markedly increased steady-state mRNA expression levels of ECE-1, ECE-2, ETA and ETB receptors (each p<0.001 vs. young mice). Deletion of Gper inhibited the age dependent increase in ECE-2 and ETB receptor mRNA levels (57% and 40% reduction, respectively, each p<0.01 vs. wild-type mice), whereas gene expression of prepro ET-1, ECE-1, and the ETA receptor was unaffected in Gper(-/-) mice. SIGNIFICANCE: We identified a novel regulatory mechanism through which the endogenous Gper facilitates the age-dependent increase in myocardial expression of ECE-2 and the ETB receptor, which is compatible with an activating role of GPER for the local endothelin system with aging. Targeting GPER signaling by selective antagonists may therefore be considered a new therapeutic approach to reduce age-dependent increased ET-1 activity and the associated development of left ventricular hypertrophy, fibrosis and heart failure. PMID- 26880535 TI - Pharmacological inhibition of galectin-1 by lactulose alleviates weight gain in diet-induced obese rats. AB - AIMS: Galectin-1 (GAL1) is an important member of the lectin family with a carbohydrate recognition domain and has recently been demonstrated to be involved in adipose metabolism. In the present study, we investigated the effects of targeted inhibition of GAL1 by its binding inhibitor lactulose under high fat diet (HFD)-induced obesity. MAIN METHODS: Effects of targeted inhibition of GAL1 by lactulose on lipid metabolism were investigated in vitro and in vivo. Changes in lipogenic capacity in lactulose-treated adipocytes were demonstrated by Oil Red O staining, triglyceride quantification and major adipogenic marker expression patterns. After lactulose treatment in Sprague-Dawley rats, various important body weight parameters, food efficiency, plasma metabolic parameters (glucose, ALT, free fatty acid, triglycerides, leptin, and insulin) and metabolic protein expression patterns were evaluated. KEY FINDINGS: Lactulose treatment reduced adipogenesis and fat accumulation in vitro by down-regulation of major adipogenic transcription factors such as C/EBPalpha and PPARgamma. In vivo treatment of lactulose to 5-week-old Sprague-Dawley male rats significantly alleviated HFD-induced body weight gain and food efficiency as well as improved plasma and other metabolic parameters. In addition, lactulose treatment down regulated major adipogenic marker proteins (C/EBPalpha and PPARgamma) in adipose tissue as well as stimulated expression of proteins involved in energy expenditure and lipolysis (ATP5B, COXIV, HSL, and CPT1). SIGNIFICANCE: In conclusion, reduced adipogenesis and increased energy expenditure mediated by lactulose treatment synergistically contribute to alleviation of HFD-induced body weight gain. Therefore, pharmaceutical targeting of GAL1 using lactulose would be a novel therapeutic approach for the treatment of obesity. PMID- 26880536 TI - Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy. AB - BACKGROUND: Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. OBJECTIVES: The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. METHODS: A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. RESULTS: An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. CONCLUSIONS: The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26880537 TI - A novel salt-inducible vector for efficient expression and secretion of heterologous proteins in Bacillus subtilis. AB - Bacillus subtilis is commonly used as a host for heterologous protein production via plasmid-based expression system. In order to improve product safety, avoid carbon catabolite repression and lower production cost, a novel salt-inducible vector, pSaltExSePR5, was developed based on a natural plasmid of Lactobacillus plantarum BCC9546. Salt-inducible promoter opuAA and a DNA fragment encoding a signal peptide of subtilisin E (SubE) were sequentially added to the core shuttle vector to facilitate expression and secretion of a target protein in B. subtilis. To evaluate the effectiveness of this system under salt induction, a protease gene from Halobacillus sp. without its native signal sequence was inserted in the pSaltExSePR5 plasmid downstream of SubE signal sequence and transformed into B. subtilis WB800. Protease activities from cell-free supernatants of the recombinant bacteria cultures induced with 0.5-6% NaCl were analyzed. The highest protease activity of 9.1 U/ml was obtained after induction with 4% NaCl, while the non-induced culture exhibited activity of 0.128 U/ml. The results demonstrated that pSaltExSePR5 provides an alternative vector for efficient and simple production of heterologous proteins in B. subtilis with a safer and more economic inducer. PMID- 26880538 TI - Continuous flocculation-sedimentation for harvesting Nannochloropsis salina biomass. AB - A continuous flow process is developed for recovery of the biomass of the marine microalga Nannochloropsis salina. Flocculation-sedimentation is used to recover the biomass from an algal suspension with an initial dry biomass concentration of 0.5 g L(-1), as would be typical of a raceway-based biomass production system. More than 85% of the biomass initially in suspension could be settled by gravity in a flocculation-sedimentation device with a total residence time of ~148 min. Aluminum sulfate was used as an inexpensive, readily available and safe flocculant. The optimal flocculant dosage (as Al2(SO4)3) was 229 mg L(-1). Relative to a highly effective 62-min batch flocculation-sedimentation process for the same alga and flocculant, the continuous flow operation took longer and required nearly double the flocculant dose. The design of the flocculation sedimentation system is explained. PMID- 26880539 TI - Biosynthesis of fluorescent CdS nanocrystals with semiconductor properties: Comparison of microbial and plant production systems. AB - This study investigated fission yeast (Schizosaccharomyces pombe) and hairy roots of tomato (Solanum lycopersicum) as in vitro production vehicles for biological synthesis of CdS quantum dots. Cd added during the mid-growth phase of the cultures was detoxified within the biomass into inorganic sulphide-containing complexes with the quantum confinement properties of semiconductor nanocrystals. Significant differences were found between the two host systems in terms of nanoparticle production kinetics, yield and quality. The much slower growth rate of hairy roots compared with yeast is a disadvantage for commercial scaled-up production. Nanoparticle extraction from the biomass was less effective for the roots: 19% of the Cd present in the hairy roots was recovered after extraction compared with 34% for the yeast. The overall yield of CdS quantum dots was also lower for the roots: relative to the amount of Cd taken up into the biomass, 8.5% was recovered in yeast gel filtration fractions exhibiting quantum dot properties whereas the result for hairy roots was only 0.99%. Yeast-produced CdS crystallites were somewhat smaller with diameters of approximately 2-6 nm compared with those of 4-10nm obtained from the roots. The average ratio of inorganic sulphide to Cd for the purified and size-fractionated particles was 0.44 for the yeast and 1.6 for the hairy roots. Despite the limitations associated with hairy roots in terms of culture kinetics and product yield, this system produced CdS nanoparticles with enhanced photostability and 3.7-13-fold higher fluorescence quantum efficiency compared with those generated by yeast. This work demonstrates that the choice of cellular host can have a significant effect on nanoparticle functional properties as well as on the bioprocessing aspects of biological quantum dot synthesis. PMID- 26880540 TI - The use of real-time polymerase chain reaction with high resolution melting (real time PCR-HRM) analysis for the detection and discrimination of nematodes Bursaphelenchus xylophilus and Bursaphelenchus mucronatus. AB - The real-time PCR-HRM analysis was developed for the detection and discrimination of the quarantine nematode Bursaphelenchus xylophilus and Bursaphelenchus mucronatus. A set of primers was designed to target the ITS region of rDNA. The results have demonstrated that this analysis is a valuable tool for differentiation of these both species. PMID- 26880541 TI - A randomized controlled trial protocol testing a decision support intervention for older patients with advanced kidney disease. AB - AIM: To assess the effectiveness of a decision support intervention using a pragmatic single blind Randomized Controlled Trial. BACKGROUND: Worldwide the proportion of older people (aged 65 years and over) is rising. This population is known to have a higher prevalence of chronic diseases including chronic kidney disease. The resultant effect of the changing health landscape is seen in the increase in older patients (aged >=65 years) commencing on dialysis. Emerging evidence suggests that for some older patients dialysis may provide minimal benefit. In a majority of renal units non-dialysis management is offered as an alternative to undertaking dialysis. Research regarding decision-making support that is required to assist this population in choosing between dialysis or non dialysis management is limited. DESIGN: A multisite single blinded pragmatic randomized controlled trial is proposed. METHODS: Patients will be recruited from four Queensland public hospitals and randomizd into either the control or intervention group. The decision support intervention is multimodal and includes counselling provided by a trained nurse. The comparator is standard decision making support. The primary outcomes are decisional regret and decisional conflict. Secondary outcomes are improved knowledge and quality of life. Ethics approval obtained November 2014. CONCLUSION: This is one of the first randomized controlled trials assessing a decision support intervention in older people with advance chronic kidney disease. The results may provide guidance for clinicians in future approaches to assist this population in decision-making to ensure reduced decisional regret and decisional conflict. PMID- 26880542 TI - Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock. AB - In vertebrate development, the sequential and rhythmic segmentation of the body axis is regulated by a "segmentation clock". This clock is comprised of a population of coordinated oscillating cells that together produce rhythmic gene expression patterns in the embryo. Whether individual cells autonomously maintain oscillations, or whether oscillations depend on signals from neighboring cells is unknown. Using a transgenic zebrafish reporter line for the cyclic transcription factor Her1, we recorded single tailbud cells in vitro. We demonstrate that individual cells can behave as autonomous cellular oscillators. We described the observed variability in cell behavior using a theory of generic oscillators with correlated noise. Single cells have longer periods and lower precision than the tissue, highlighting the role of collective processes in the segmentation clock. Our work reveals a population of cells from the zebrafish segmentation clock that behave as self-sustained, autonomous oscillators with distinctive noisy dynamics. PMID- 26880543 TI - A synergy-based hand control is encoded in human motor cortical areas. AB - How the human brain controls hand movements to carry out different tasks is still debated. The concept of synergy has been proposed to indicate functional modules that may simplify the control of hand postures by simultaneously recruiting sets of muscles and joints. However, whether and to what extent synergic hand postures are encoded as such at a cortical level remains unknown. Here, we combined kinematic, electromyography, and brain activity measures obtained by functional magnetic resonance imaging while subjects performed a variety of movements towards virtual objects. Hand postural information, encoded through kinematic synergies, were represented in cortical areas devoted to hand motor control and successfully discriminated individual grasping movements, significantly outperforming alternative somatotopic or muscle-based models. Importantly, hand postural synergies were predicted by neural activation patterns within primary motor cortex. These findings support a novel cortical organization for hand movement control and open potential applications for brain-computer interfaces and neuroprostheses. PMID- 26880544 TI - The horizontally-acquired response regulator SsrB drives a Salmonella lifestyle switch by relieving biofilm silencing. AB - A common strategy by which bacterial pathogens reside in humans is by shifting from a virulent lifestyle, (systemic infection), to a dormant carrier state. Two major serovars of Salmonella enterica, Typhi and Typhimurium, have evolved a two component regulatory system to exist inside Salmonella-containing vacuoles in the macrophage, as well as to persist as asymptomatic biofilms in the gallbladder. Here we present evidence that SsrB, a transcriptional regulator encoded on the SPI-2 pathogenicity-island, determines the switch between these two lifestyles by controlling ancestral and horizontally-acquired genes. In the acidic macrophage vacuole, the kinase SsrA phosphorylates SsrB, and SsrB~P relieves silencing of virulence genes and activates their transcription. In the absence of SsrA, unphosphorylated SsrB directs transcription of factors required for biofilm formation specifically by activating csgD (agfD), the master biofilm regulator by disrupting the silenced, H-NS-bound promoter. Anti-silencing mechanisms thus control the switch between opposing lifestyles. PMID- 26880545 TI - A circuit mechanism for the propagation of waves of muscle contraction in Drosophila. AB - Animals move by adaptively coordinating the sequential activation of muscles. The circuit mechanisms underlying coordinated locomotion are poorly understood. Here, we report on a novel circuit for the propagation of waves of muscle contraction, using the peristaltic locomotion of Drosophila larvae as a model system. We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave. The excitatory neurons (A27h) are premotor and necessary only for forward locomotion, and are modulated by stretch receptors and descending inputs. The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation. The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion. PMID- 26880546 TI - Active sensing in the categorization of visual patterns. AB - Interpreting visual scenes typically requires us to accumulate information from multiple locations in a scene. Using a novel gaze-contingent paradigm in a visual categorization task, we show that participants' scan paths follow an active sensing strategy that incorporates information already acquired about the scene and knowledge of the statistical structure of patterns. Intriguingly, categorization performance was markedly improved when locations were revealed to participants by an optimal Bayesian active sensor algorithm. By using a combination of a Bayesian ideal observer and the active sensor algorithm, we estimate that a major portion of this apparent suboptimality of fixation locations arises from prior biases, perceptual noise and inaccuracies in eye movements, and the central process of selecting fixation locations is around 70% efficient in our task. Our results suggest that participants select eye movements with the goal of maximizing information about abstract categories that require the integration of information from multiple locations. PMID- 26880547 TI - Nanoscale dynamics of synaptic vesicle trafficking and fusion at the presynaptic active zone. AB - The cytomatrix at the active zone (CAZ) is a macromolecular complex that facilitates the supply of release-ready synaptic vesicles to support neurotransmitter release at synapses. To reveal the dynamics of this supply process in living synapses, we used super-resolution imaging to track single vesicles at voltage-clamped presynaptic terminals of retinal bipolar neurons, whose CAZ contains a specialized structure-the synaptic ribbon-that supports both fast, transient and slow, sustained modes of transmission. We find that the synaptic ribbon serves a dual function as a conduit for diffusion of synaptic vesicles and a platform for vesicles to fuse distal to the plasma membrane itself, via compound fusion. The combination of these functions allows the ribbon type CAZ to achieve the continuous transmitter release required by synapses of neurons that carry tonic, graded visual signals in the retina. PMID- 26880548 TI - Involvement of the Acyl-CoA binding domain containing 7 in the control of food intake and energy expenditure in mice. AB - Acyl-CoA binding domain-containing 7 (Acbd7) is a paralog gene of the diazepam binding inhibitor/Acyl-CoA binding protein in which single nucleotide polymorphism has recently been associated with obesity in humans. In this report, we provide converging evidence indicating that a splice variant isoform of the Acbd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate nucleus (ARC). We have demonstrated that the ARC ACBD7 isoform was produced and processed into a bioactive peptide referred to as nonadecaneuropeptide (NDN) in response to catabolic signals. We have characterized NDN as a potent anorexigenic signal acting through an uncharacterized endozepine G protein-coupled receptor and subsequently via the melanocortin system. Our results suggest that ACBD7-producing neurons participate in the hypothalamic leptin signalling pathway. Taken together, these data suggest that ACBD7-producing neurons are involved in the hypothalamic control exerted on food intake and energy expenditure by the leptin-melanocortin pathway. PMID- 26880550 TI - Comparative Genomics: One for all. AB - Using a common analysis pipeline to compare data from three major lineages of complex eukaryotes reveals that transcription seems to evolve at a common rate. PMID- 26880549 TI - Membrane palmitoylated protein 2 is a synaptic scaffold protein required for synaptic SK2-containing channel function. AB - Mouse CA1 pyramidal neurons express apamin-sensitive SK2-containing channels in the post-synaptic membrane, positioned close to NMDA-type (N-methyl-D-aspartate) glutamate receptors. Activated by synaptically evoked NMDAR-dependent Ca(2+) influx, the synaptic SK2-containing channels modulate excitatory post-synaptic responses and the induction of synaptic plasticity. In addition, their activity- and protein kinase A-dependent trafficking contributes to expression of long-term potentiation (LTP). We have identified a novel synaptic scaffold, MPP2 (membrane palmitoylated protein 2; p55), a member of the membrane-associated guanylate kinase (MAGUK) family that interacts with SK2-containing channels. MPP2 and SK2 co-immunopurified from mouse brain, and co-immunoprecipitated when they were co expressed in HEK293 cells. MPP2 is highly expressed in the post-synaptic density of dendritic spines on CA1 pyramidal neurons. Knocking down MPP2 expression selectively abolished the SK2-containing channel contribution to synaptic responses and decreased LTP. Thus, MPP2 is a novel synaptic scaffold that is required for proper synaptic localization and function of SK2-containing channels. PMID- 26880552 TI - Large-scale microtubule networks contract quite well. AB - The quantitative investigation of how networks of microtubules contract can boost our understanding of actin biology. PMID- 26880551 TI - TBP/TFIID-dependent activation of MyoD target genes in skeletal muscle cells. AB - Change in the identity of the components of the transcription pre-initiation complex is proposed to control cell type-specific gene expression. Replacement of the canonical TFIID-TBP complex with TRF3/TBP2 was reported to be required for activation of muscle-gene expression. The lack of a developmental phenotype in TBP2 null mice prompted further analysis to determine whether TBP2 deficiency can compromise adult myogenesis. We show here that TBP2 null mice have an intact regeneration potential upon injury and that TBP2 is not expressed in established C2C12 muscle cell or in primary mouse MuSCs. While TFIID subunits and TBP are downregulated during myoblast differentiation, reduced amounts of these proteins form a complex that is detectable on promoters of muscle genes and is essential for their expression. This evidence demonstrates that TBP2 does not replace TBP during muscle differentiation, as previously proposed, with limiting amounts of TFIID-TBP being required to promote muscle-specific gene expression. PMID- 26880553 TI - Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin. AB - Venom toxins are invaluable tools for exploring the structure and mechanisms of ion channels. Here, we solve the structure of double-knot toxin (DkTx), a tarantula toxin that activates the heat-activated TRPV1 channel. We also provide improved structures of TRPV1 with and without the toxin bound, and investigate the interactions of DkTx with the channel and membranes. We find that DkTx binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. We also show that DkTx partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. Finally, we find that the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation. Collectively, our findings reveal a novel mode of toxin-channel recognition that has important implications for the mechanism of thermosensation. PMID- 26880554 TI - Neuronal processing of noxious thermal stimuli mediated by dendritic Ca(2+) influx in Drosophila somatosensory neurons. AB - Adequate responses to noxious stimuli causing tissue damages are essential for organismal survival. Class IV neurons in Drosophila larvae are polymodal nociceptors responsible for thermal, mechanical, and light sensation. Importantly, activation of Class IV provoked distinct avoidance behaviors, depending on the inputs. We found that noxious thermal stimuli, but not blue light stimulation, caused a unique pattern of Class IV, which were composed of pauses after high-frequency spike trains and a large Ca(2+) rise in the dendrite (the Ca(2+) transient). Both these responses depended on two TRPA channels and the L-type voltage-gated calcium channel (L-VGCC), showing that the thermosensation provokes Ca(2+) influx. The precipitous fluctuation of firing rate in Class IV neurons enhanced the robust heat avoidance. We hypothesize that the Ca(2+) influx can be a key signal encoding a specific modality. PMID- 26880556 TI - Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. AB - Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via alpha7 containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep. PMID- 26880558 TI - Evolution: How the zebrafish got its stripes. AB - Live-cell imaging and genetic tools reveal a new way in which pigment cells communicate in zebrafish. PMID- 26880557 TI - Non-canonical antagonism of PI3K by the kinase Itpkb delays thymocyte beta selection and renders it Notch-dependent. AB - beta-selection is the most pivotal event determining alphabeta T cell fate. Here, surface-expression of a pre-T cell receptor (pre-TCR) induces thymocyte metabolic activation, proliferation, survival and differentiation. Besides the pre-TCR, beta-selection also requires co-stimulatory signals from Notch receptors - key cell fate determinants in eukaryotes. Here, we show that this Notch-dependence is established through antagonistic signaling by the pre-TCR/Notch effector, phosphoinositide 3-kinase (PI3K), and by inositol-trisphosphate 3-kinase B (Itpkb). Canonically, PI3K is counteracted by the lipid-phosphatases Pten and Inpp5d/SHIP-1. In contrast, Itpkb dampens pre-TCR induced PI3K/Akt signaling by producing IP4, a soluble antagonist of the Akt-activating PI3K-product PIP3. Itpkb(-/-) thymocytes are pre-TCR hyperresponsive, hyperactivate Akt, downstream mTOR and metabolism, undergo an accelerated beta-selection and can develop to CD4(+)CD8(+) cells without Notch. This is reversed by inhibition of Akt, mTOR or glucose metabolism. Thus, non-canonical PI3K-antagonism by Itpkb restricts pre TCR induced metabolic activation to enforce coincidence-detection of pre-TCR expression and Notch-engagement. PMID- 26880555 TI - Regulatory polymorphisms modulate the expression of HLA class II molecules and promote autoimmunity. AB - Targeted sequencing of sixteen SLE risk loci among 1349 Caucasian cases and controls produced a comprehensive dataset of the variations causing susceptibility to systemic lupus erythematosus (SLE). Two independent disease association signals in the HLA-D region identified two regulatory regions containing 3562 polymorphisms that modified thirty-seven transcription factor binding sites. These extensive functional variations are a new and potent facet of HLA polymorphism. Variations modifying the consensus binding motifs of IRF4 and CTCF in the XL9 regulatory complex modified the transcription of HLA-DRB1, HLA-DQA1 and HLA-DQB1 in a chromosome-specific manner, resulting in a 2.5-fold increase in the surface expression of HLA-DR and DQ molecules on dendritic cells with SLE risk genotypes, which increases to over 4-fold after stimulation. Similar analyses of fifteen other SLE risk loci identified 1206 functional variants tightly linked with disease-associated SNPs and demonstrated that common disease alleles contain multiple causal variants modulating multiple immune system genes. PMID- 26880559 TI - Prediction of primary somatosensory neuron activity during active tactile exploration. AB - Primary sensory neurons form the interface between world and brain. Their function is well-understood during passive stimulation but, under natural behaving conditions, sense organs are under active, motor control. In an attempt to predict primary neuron firing under natural conditions of sensorimotor integration, we recorded from primary mechanosensory neurons of awake, head-fixed mice as they explored a pole with their whiskers, and simultaneously measured both whisker motion and forces with high-speed videography. Using Generalised Linear Models, we found that primary neuron responses were poorly predicted by whisker angle, but well-predicted by rotational forces acting on the whisker: both during touch and free-air whisker motion. These results are in apparent contrast to previous studies of passive stimulation, but could be reconciled by differences in the kinematics-force relationship between active and passive conditions. Thus, simple statistical models can predict rich neural activity elicited by natural, exploratory behaviour involving active movement of sense organs. PMID- 26880560 TI - Bitter taste receptors confer diverse functions to neurons. AB - Bitter compounds elicit an aversive response. In Drosophila, bitter-sensitive taste neurons coexpress many members of the Gr family of taste receptors. However, the molecular logic of bitter signaling is unknown. We used an in vivo expression approach to analyze the logic of bitter taste signaling. Ectopic or overexpression of bitter Grs increased endogenous responses or conferred novel responses. Surprisingly, expression of Grs also suppressed many endogenous bitter responses. Conversely, deletion of an endogenous Gr led to novel responses. Expression of individual Grs conferred strikingly different effects in different neurons. The results support a model in which bitter Grs interact, exhibiting competition, inhibition, or activation. The results have broad implications for the problem of how taste systems evolve to detect new environmental dangers. PMID- 26880561 TI - Imaging a memory trace over half a life-time in the medial temporal lobe reveals a time-limited role of CA3 neurons in retrieval. AB - Whether retrieval still depends on the hippocampus as memories age or relies then on cortical areas remains a major controversy. Despite evidence for a functional segregation between CA1, CA3 and parahippocampal areas, their specific role within this frame is unclear. Especially, the contribution of CA3 is questionable as very remote memories might be too degraded to be used for pattern completion. To identify the specific role of these areas, we imaged brain activity in mice during retrieval of recent, early remote and very remote fear memories by detecting the immediate-early gene Arc. Investigating correlates of the memory trace over an extended period allowed us to report that, in contrast to CA1, CA3 is no longer recruited in very remote retrieval. Conversely, we showed that parahippocampal areas are then maximally engaged. These results suggest a shift from a greater contribution of the trisynaptic loop to the temporoammonic pathway for retrieval. PMID- 26880562 TI - Aurkb/PP1-mediated resetting of Oct4 during the cell cycle determines the identity of embryonic stem cells. AB - Pluripotency transcription programs by core transcription factors (CTFs) might be reset during M/G1 transition to maintain the pluripotency of embryonic stem cells (ESCs). However, little is known about how CTFs are governed during cell cycle progression. Here, we demonstrate that the regulation of Oct4 by Aurora kinase b (Aurkb)/protein phosphatase 1 (PP1) during the cell cycle is important for resetting Oct4 to pluripotency and cell cycle genes in determining the identity of ESCs. Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle. Aurkb phosphor-mimetic and PP1 binding-deficient mutations in Oct4 alter the cell cycle, effect the loss of pluripotency in ESCs, and decrease the efficiency of somatic cell reprogramming. Our findings provide evidence that the cell cycle is linked directly to pluripotency programs in ESCs. PMID- 26880564 TI - Phototaxis: Life in focus. AB - Single-celled photosynthetic bacteria determine the direction of incoming light by acting as lenses. PMID- 26880563 TI - Identity of neocortical layer 4 neurons is specified through correct positioning into the cortex. AB - Many cell-intrinsic mechanisms have been shown to regulate neuronal subtype specification in the mammalian neocortex. However, how much cell environment is crucial for subtype determination still remained unclear. Here, we show that knockdown of Protocadherin20 (Pcdh20), which is expressed in post-migratory neurons of layer 4 (L4) lineage, caused the cells to localize in L2/3. The ectopically positioned "future L4 neurons" lost their L4 characteristics but acquired L2/3 characteristics. Knockdown of a cytoskeletal protein in the future L4 neurons, which caused random disruption of positioning, also showed that those accidentally located in L4 acquired the L4 characteristics. Moreover, restoration of positioning of the Pcdh20-knockdown neurons into L4 rescued the specification failure. We further suggest that the thalamocortical axons provide a positional cue to specify L4 identity. These results suggest that the L4 identity is not completely determined at the time of birth but ensured by the surrounding environment after appropriate positioning. PMID- 26880567 TI - Effect of Nanofiller Loading on Cure Efficiency and Potential Color Change of Model Composites. AB - OBJECTIVES: To evaluate the effect of nanofiller loading on cure efficiency and potential color change of experimental composites. MATERIALS AND METHODS: Four different polymeric materials were produced using the same organic matrix blend. To this matrix, different amounts of 0.05 MUm fumed silica filler were added: no filler, 13, 52, and 65wt%. Fourier transform infrared spectroscopy was used to evaluate the degree of conversion (DC) for each composite using near-IR analysis, and spectrophotometry according to CIELab chromatic space was used to evaluate the color change.To induce color change, composites were artificially aged with exposure to cycles of UV-B light for 300 hours. Trasmission electron microscopy was used to illustrate nanoffiler aglomeration in the resin matrix. Data were analyzed using correlation analysis (alpha = 0.05). RESULTS: There was an excellent inverse linear correlation between filler wt% and either DC or color change. Greater changes to red (+Deltaa) and yellow (+Deltab) were observed as the filler wt% increased. CONCLUSIONS: A higher percentage of nano-sized filler particles in dental resin composites directly affects their cure efficiency and potential for color change. CLINICAL SIGNIFICANCE: The increase in filler particle loading negatively affected monomer conversion and color stability of resin-based composites. As reduced filler loading results in poorer mechanical properties, to enhance color stability, resin-based composites should be formulated by making the refractive index of the polymeric matrix more closely match that of the filler throughout the polymerization process. (J Esthet Restor Dent, 2016). PMID- 26880568 TI - Maskless, High-Precision, Persistent, and Extreme Wetting-Contrast Patterning in an Environmental Scanning Electron Microscope. AB - A maskless and programmable direct electron beam writing method is reported for making high-precision superhydrophilic-superhydrophobic wetting patterns with 152 degrees contact angle contrast using an environmental scanning electron microscope (ESEM). The smallest linewidth achieved is below 1 MUm. The reported effects of the electron beam induced local plasma may also influence a variety of microscopic wetting studies in ESEM. PMID- 26880565 TI - Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein. AB - Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by folding into the RNA-binding cleft. Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals. PMID- 26880569 TI - Control of Surface Plasmon Resonance of Au/SnO2 by Modification with Ag and Cu for Photoinduced Reactions under Visible-Light Irradiation over a Wide Range. AB - Gold particles supported on tin(IV) oxide (0.2 wt% Au/SnO2) were modified with copper and silver by the multistep photodeposition method. Absorption around lambda=550 nm, attributed to surface plasmon resonance (SPR) of Au, gradually shifted to longer wavelengths on modification with Cu and finally reached lambda=620 nm at 0.8 wt% Cu. On the other hand, the absorption shifted to shorter wavelength with increasing amount of Ag and reached lambda=450 nm at 0.8 wt% Ag. These Cu- and Ag-modified 0.2 wt% Au/SnO2 materials (Cu-Au/SnO2 and Ag-Au/SnO2) and 1.0 wt% Au/SnO2 were used for mineralization of formic acid to carbon dioxide in aqueous suspension under irradiation with visible light from a xenon lamp and three kinds of light-emitting diodes with different wavelengths. The reaction rates for the mineralization of formic acid over these materials depend on the wavelength of light. Apparent quantum efficiencies of Cu-Au/SnO2, Au/SnO2, and Ag Au/SnO2 reached 5.5% at 625 nm, 5.8% at 525 nm, and 5.1% at 450 nm, respectively. These photocatalysts can also be used for selective oxidation of alcohols to corresponding carbonyl compounds in aqueous solution under visible-light irradiation. Broad responses to visible light in formic acid mineralization and selective alcohol oxidation were achieved when the three materials were used simultaneously. PMID- 26880570 TI - Clinical Outcome of First- vs Second-Generation DES According to DAPT Duration: Results of ARCTIC-Generation. AB - There is an apparent benefit with extension of dual antiplatelet therapy (DAPT) beyond 1 year after implantation of drug-eluting stents (DES). Assessment by a Double Randomization of a Conventional Antiplatelet Strategy vs a Monitoring Guided Strategy for Drug-Eluting Stent Implantation, and of Treatment Interruption vs Continuation One Year After Stenting (ARCTIC)-Generation assessed whether there is a difference of outcome between first- vs second-generation DES and if there is an interaction with DAPT duration in the ARCTIC-Interruption study. ARCTIC-Interruption randomly allocated 1259 patients 1 year after stent implantation to a strategy of interruption of DAPT (n = 624), in which aspirin antiplatelet treatment only was maintained, or DAPT continuation (n = 635) for 6 to 18 additional months. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. A total of 520 and 722 patients received a first- and a second-generation DES, respectively. After a median follow-up of 17 months (interquartile range, 15-18 months) after randomization, the primary endpoint occurred in 32 (6.2%) and 19 (2.6%) patients with first- and second-generation DES, respectively (hazard ratio: 2.31, 95% confidence interval: 1.31-4.07, P = 0.004). This was observed irrespective of the strategy of interruption or continuation of DAPT and timing of study recruitment. Major bleeding events occurred in 4 (0.8%) and 3 patients (0.4%) with first- and second-generation DES, respectively (hazard ratio: 1.79, 95% confidence interval: 0.40-8.02, P = 0.44). Results did not change after multiple adjustments for potential confounding variables. ARCTIC-Generation showed worse clinical outcome with first- vs second-generation DES, a difference that appeared to persist even with prolonged DAPT. PMID- 26880572 TI - A successful high-visibility enforcement intervention targeting underage drinking drivers. AB - AIMS: To measure the effectiveness of a high-visibility enforcement campaign to reduce rates of underage drinking and driving. DESIGN: Mixed-model analysis compares rates of drinking and driving (1) between the baseline and intervention period and (2) between the baseline and follow-up period. The impact of the intervention was evaluated using roadside surveys and web surveys. SETTING: Two college-town communities in the mid-Atlantic region of the United States. PARTICIPANTS: Study participants consisted of 6825 drivers stopped, interviewed and breathalyzed on weekend nights. Web survey data were collected from 2061 students from large state universities in each community. INTERVENTION: Increased high-visibility enforcement of drinking and driving laws, featuring the use of passive alcohol sensors by police, along with a coordinated publicity campaign. MEASURES: Roadside surveys measured breath alcohol concentrations (BrAC) of drivers. The web surveys measured self-reported drinking. FINDINGS: Mixed-model analysis revealed a statistically significant reduction in drivers with BrACs >= 0.08 g/dl during the intervention and follow-up periods, F(2, 5744) = 6.5, P < 0.01. The web-survey revealed that students under age 21 also reported significantly less driving after drinking during the intervention and follow-up periods, F(2, 1767) = 4.6, P < 0.01. CONCLUSIONS: A high-visibility enforcement campaign targeting underage drinking and driving appeared to reduce both underage driving after drinking among US college students as well as drunk driving (breath alcohol concentration >= 0.08 g/dl) at any age.. PMID- 26880571 TI - Exploring self-rated health among adolescents: a think-aloud study. AB - BACKGROUND: Despite extensive use of self-rated health questions in youth studies, little is known about what such questions capture among adolescents. Hence, the aim of this study was to explore how adolescents interpret and reason when answering a question about self-rated health. METHODS: A qualitative study using think-aloud interviews explored the question, "How do you feel most of the time?", using five response options ("Very good", "Rather good", "Neither good, nor bad", "Rather bad", and "Very bad"). The study involved 58 adolescents (29 boys and 29 girls) in lower secondary school (7th grade) and upper secondary school (12th grade) in Sweden. RESULTS: Respondents' interpretations of the question about how they felt included social, mental, and physical aspects. Gender differences were found primarily in that girls emphasized stressors, while age differences were reflected mainly in the older respondents' inclusion of a wider variety of influences on their assessments. The five response options all demonstrated differences in self-rated health, and the respondents' understanding of the middle option, "Neither good, nor bad", varied widely. In the answering of potential sensitive survey questions, rationales for providing honest or biased answers were described. CONCLUSIONS: The use of a self-rated health question including the word 'feel' captured a holistic view of health among adolescents. Differences amongst response options should be acknowledged when analyzing self rated health questions. If anonymity is not feasible when answering questions on self-rated health, a high level of privacy is recommended to increase the likelihood of reliability. PMID- 26880573 TI - Enhancing hepatic fibrosis in spontaneously hypertensive rats fed a choline deficient diet: a follow-up report on long-term effects of oxidative stress in non-alcoholic fatty liver disease. AB - BACKGROUND: We previously reported a model of non-alcoholic fatty liver disease (NAFLD) using spontaneously hypertensive rats (SHRs), fed a choline-deficient (CD) diet for 5 weeks, that hepatic steatosis but not fibrosis is developed through oxidative stress. To determine the relationship between hypertension and hepatic fibrosis in NAFLD, we examined whether long-term CD diet leads to hepatic fibrosis through oxidative stress. METHODS: Eight-week-old male SHR and normotensive Wistar Kyoto rats (WKYs) were fed a CD diet for 5 or 20 weeks, then liver histology and hepatic expression of genes related to lipid metabolism, fibrosis, and oxidative stress were assessed. Oxidative stress was assessed by hepatic thiobarbituric acid reactive substance (TBARS) levels. RESULTS: After 5 weeks on CD diet, prominent hepatic steatosis and decrease in expression of genes for lipid metabolism were observed in SHRs as compared with WKYs. SHRs on a CD diet demonstrated a downregulated expression of genes for antioxidants, along with significant increases in hepatic TBARS. After 20 weeks on CD diet, SHRs demonstrated severe liver fibrosis and upregulated expressions of genes for fibrosis when compared with WKY. CONCLUSION: Hypertension precipitated hepatic steatosis, and further, acts as an enhancer in NAFLD progression to liver fibrosis through oxidative stress. PMID- 26880574 TI - Sinonasal small cell neuroendocrine carcinoma: a systematic review of 80 patients. AB - BACKGROUND: The objective of this study was to review the published literature related to sinonasal small cell neuroendocrine carcinomas (SCNECs). Clinical presentation, demographics, treatment, and outcomes of this uncommon disease are reported. METHODS: A systematic review of studies for sinonasal SCNECs in PubMed and Ovid databases from 1970 to 2014 was conducted. Bibliographies of selected articles were also examined. Articles were examined for patient data that reported disease outcome. RESULTS: Thirty-four articles were included in this analysis, comprising a total of 80 cases. The mean age of presentation was 53.0 years. Nasal obstruction (53.8%) and epistaxis (48.8%) were the most common presenting symptoms. The nasal cavity and septum (32.5%) was the most common site of involvement. Seventy percent of patients presented with American Joint Committee on Cancer (AJCC) stage IV disease. Combination chemotherapy and radiation therapy was the most common treatment modality, used in 21 cases (26.3%). The second and third most common treatment modalities was combination surgery and chemoradiation therapy (21.3%), and surgery alone (18.8%), respectively. A total of 37 patients (46.3%) were alive after a mean follow-up of 30.8 months (median 15.5 months), independent of treatment modality. Of the treatment modalities, multimodality therapy remained the most common therapy. CONCLUSION: This review contains the largest pool of sinonasal SCNEC patients to date. Sinonasal SCNEC is a rare and aggressive neoplasm, and there is currently no standard of care for treatment. Various treatment modalities have been employed. Our systematic review suggests that multimodality therapy remains the most common treatment of sinonasal SCNEC. PMID- 26880575 TI - Determinants of Successful Methicillin-Resistant Staphylococcus aureus Decolonization. PMID- 26880576 TI - RNase H2 catalytic core Aicardi-Goutieres syndrome-related mutant invokes cGAS STING innate immune-sensing pathway in mice. AB - The neuroinflammatory autoimmune disease Aicardi-Goutieres syndrome (AGS) develops from mutations in genes encoding several nucleotide-processing proteins, including RNase H2. Defective RNase H2 may induce accumulation of self-nucleic acid species that trigger chronic type I interferon and inflammatory responses, leading to AGS pathology. We created a knock-in mouse model with an RNase H2 AGS mutation in a highly conserved residue of the catalytic subunit, Rnaseh2a(G37S/G37S) (G37S), to understand disease pathology. G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice. Importantly, we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS-STING signaling pathway. Ablation of STING in the G37S mice results in partial rescue of the perinatal lethality, with viable mice exhibiting white spotting on their ventral surface. We believe that the G37S knock-in mouse provides an excellent animal model for studying RNASEH2-associated autoimmune diseases. PMID- 26880579 TI - Synthesis and Reactivity of a Bio-inspired Dithiolene Ligand and its Mo Oxo Complex. AB - An original synthesis of the fused pyranoquinoxaline dithiolene ligand qpdt(2-) is discussed in detail. The most intriguing step is the introduction of the dithiolene moiety by Pd-catalyzed carbon-sulfur coupling. The corresponding Mo(IV)O complex (Bu4N)2 [MoO(qpdt)2] (2) underwent reversible protonation in a strongly acidic medium and remained stable under anaerobic conditions. Besides, 2 was found to be very sensitive towards oxygen, as upon oxidation it formed a planar dithiin derivative. Moreover, the qpdt(2-) ligand in the presence of [MoCl4 (tBuNC)2] formed a tetracyclic structure. The products resulting from the unique reactivity of qpdt(2-) were characterized by X-ray diffraction, mass spectrometry, NMR spectroscopy, UV/Vis spectroscopy, and electrochemistry. Plausible mechanisms for the formation of these products are also proposed. PMID- 26880577 TI - Functional screen identifies regulators of murine hematopoietic stem cell repopulation. AB - Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251. Knockdown of each of these genes yielded a loss of function, except in the cases of Armcx1 and Gprasp2, whose loss enhanced hematopoietic stem cell (HSC) repopulation. The discovery of multiple genes regulating vesicular trafficking, cell surface receptor turnover, and secretion of extracellular matrix components suggests active cross talk between HSCs and the niche and that HSCs may actively condition the niche to promote engraftment. We validated that Foxa3 is required for HSC repopulating activity, as Foxa3(-/-) HSC fails to repopulate ablated hosts efficiently, implicating for the first time Foxa genes as regulators of HSPCs. We further show that Foxa3 likely regulates the HSC response to hematologic stress. Each gene discovered here offers a window into the novel processes that regulate stable HSPC engraftment into an ablated host. PMID- 26880578 TI - Antibodies against a secreted product of Staphylococcus aureus trigger phagocytic killing. AB - Host immunity against bacteria typically involves antibodies that recognize the microbial surface and promote phagocytic killing. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of lethal bloodstream infection; however, vaccines and antibody therapeutics targeting staphylococcal surface molecules have thus far failed to achieve clinical efficacy. S. aureus secretes coagulase (Coa), which activates host prothrombin and generates fibrin fibrils that protect the pathogen against phagocytosis by immune cells. Because of negative selection, the coding sequence for the prothrombin-binding D1-D2 domain is highly variable and does not elicit cross-protective immune responses. The R domain, tandem repeats of a 27-residue peptide that bind fibrinogen, is conserved at the C terminus of all Coa molecules, but its functional significance is not known. We show here that the R domain enables bloodstream infections by directing fibrinogen to the staphylococcal surface, generating a protective fibrin shield that inhibits phagocytosis. The fibrin shield can be marked with R-specific antibodies, which trigger phagocytic killing of staphylococci and protect mice against lethal bloodstream infections caused by a broad spectrum of MRSA isolates. These findings emphasize the critical role of coagulase in staphylococcal escape from opsonophagocytic killing and as a protective antigen for S. aureus vaccines. PMID- 26880580 TI - Filtering promiscuous compounds in early drug discovery: is it a good idea? AB - The use of computational filters for excluding supposedly nonspecific and promiscuous compounds from chemical libraries is a controversial issue, because many drugs used in clinics today would never reach the market if these filters were applied. In part, this conflict could be caused by the paradigm: one-drug one-target, even though it is widely agreed that drug action is a result of a complex network of biomolecular interactions. Therefore, the so-called pan assay interference compounds (PAINS) or promiscuous compounds could be in fact assay artifacts, false positives or, simply, bright chemical matter (BCM) composed of privileged scaffolds, as we propose here. Despite apparent promiscuity, BCM can be tailored into new and safe drugs after overcoming selectivity criteria. PMID- 26880581 TI - Conformational Studies and Atropisomerism Kinetics of the ALK Clinical Candidate Lorlatinib (PF-06463922) and Desmethyl Congeners. AB - Lorlatinib (PF-06463922) is an ALK/ROS1 inhibitor and is in clinical trials for the treatment of ALK positive or ROS1 positive NSCLC (i.e. specific subsets of NSCLC). One of the laboratory objectives for this molecule indicated that it would be desirable to advance a molecule which was CNS penetrant in order to treat brain metastases. From this perspective, a macrocyclic template was attractive for a number of reasons. In particular, this template reduces the number of rotatable bonds, provides the potential to shield polar surface area and reinforces binding through a restricted conformation. All of these features led to better permeability for the molecules of interest and thus increased the chance for better blood brain barrier penetration. With a CNS penetrant molecule, kinase selectivity is a key consideration particularly with regard to proteins such as TrkB, which are believed to influence cognitive function. Removal of the chiral benzylic methyl substituent from lorlatinib was perceived as not only a means to simplify synthetic complexity, but also as a strategy to further truncate the molecule of interest. Examination of the NMR of the desmethyl analogues revealed that the compound existed as a mixture of atropisomers, which proved separable by chiral SFC. The individual atropisomers were evaluated through a series of in vitro assays, and shown to have a favorable selectivity profile when compared to lorlatinib. The challenge to develop such a molecule lies in the rate at which the atropisomers interchange dictated by the energy barrier required to do this. Here, we describe the synthesis of the desmethyl macrocycles, conformational studies on the atropisomers, and the kinetics of the interconversion. In addition, the corresponding conformational studies on lorlatinib are reported providing a hypothesis for why a single diastereomer is observed when the chiral benzylic methyl group is introduced. PMID- 26880582 TI - Platinum-Copper Nanoframes: One-Pot Synthesis and Enhanced Electrocatalytic Activity. AB - Platinum-copper nanoframes were produced from copper nanoparticles by a one-pot synthesis method. The growth mechanism was thoroughly studied by experiment and theoretical calculations. Owing to the unique structure, Pt-Cu nanoframes exhibited significantly enhanced catalytic activity toward the electro-oxidation of methanol compared to commercial Pt black. PMID- 26880583 TI - Tumor suppressor NGX6 inhibits the growth and metastasis of multiple cancers. AB - Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a membrane protein primarily located in the nuclear membrane and cell membrane. Several groups reported that NGX6 gene was down-regulated in nasopharyngeal carcinoma (NPC), gastric cancer, lung cancer, liver cancer, and colorectal cancer and even less in the carcinomas with metastasis. Current studies have demonstrated that NGX6 possesses various biological functions, such as regulating protein expression of related genes, involving cell signal transduction pathways, negatively controlling cell cycle progression, inhibiting angiogenesis, and increasing the sensitivity of patients to anti-cancer drugs. Some factors regulating the expression level of NGX6 gene also have been studied. The methylation of promoter of NGX6 and histone H3K9 negatively regulates its expression, similar to the function of transcription factor special protein-1 (Sp1). However, the regulatory factor early growth response gene 1 (Egr-1) is provided with positive regulation function. This review will summarize the progress of those studies on NGX6 and elucidate the potential application of NGX6 for some malignant diseases. PMID- 26880584 TI - Hypoxia inducible factor: a potential prognostic biomarker in oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the most common oral cancer. Hypoxia inducible factor (HIF) is involved in many malignant tumors' growth and metastasis and upregulated by hypoxia, including oral cancer. Many studies have studied about the prognostic value of HIF expression in OSCC; however, they do not get the consistent results. Therefore, this study explored the correlation between the HIF expression and the prognosis of OSCC. It conducted a meta analysis of relevant publications searched in the Web of Science, PubMed, and ISI Web of Knowledge databases. Totally, this study identified 12 relevant articles reporting a total of 1112 patients. This analysis revealed a significant association between increased risk of mortality (RR = 1.20; 95 % CI 0.74-1.95; I (2) 85.4 %) and overexpression of HIFs. Furthermore, different HIF isoforms were associated with overall survival [HIF-1alpha (RR = 1.18; 95 % CI 0.66-2.11; I (2) 87.2 %) and HIF-2alpha (RR = 1.40; 95 % CI 0.93-2.09; I(2) 0.0 %)]. These results show that overexpression of HIFs, regardless of whether the HIF-1alpha or HIF 2alpha isoforms are overexpressed is significantly associated with increased risk of mortality in OSCC patients. In this study, the funnel is symmetric, suggesting existed no publication bias. PMID- 26880585 TI - Association of toll-like receptor 2 ?22 and risk for gastric cancer considering main effects and interactions with smoking: a matched case-control study from Mizoram, India. AB - Toll-like receptors (TLRs) are evolutionary conserved cell surface receptors of the innate immune system. Smoking has significant immunological effects which are mediated via TLRs on various receptor-mediated innate response pathways. Polymorphisms of TLR genes are associated with susceptibility toward various malignancies. The present study was undertaken to examine the association between TLR2 ?22 and gastric cancer. In this study, we also investigated the interaction between TLR2 ?22 and smoking. A total of 133 histologically confirmed gastric cancer cases and 266 age-sex-matched controls were selected for this study. TLR2 ?22 genotypes were determined by allele-specific polymerase chain reaction (PCR). Binary conditional logistic regression analysis was used to find the association of TLR2 ?22 with risk of gastric cancer. Logistic regression using hierarchically well-formulated models was used for interaction analysis between smoking and TLR2 ?22. Persons having TLR2 ?22 heterozygous genotype had two times increased risk of gastric cancer in multivariate logistic regression model. The interaction analysis using hierarchical logistic regression models between smoking and TLR2 ?22 by calculating separate X (2) for interaction model and only main effect model, the difference of X (2) 57.68-47.70 = 9.98 and degrees of freedom (df) 5-3 = 2, revealed significant (alpha = 0.05, df = 2) omnibus interaction. Our present study revealed TLR2 ?22 to be significantly and independently associated with gastric cancer risk in Mizoram, and there is also evidence of significant interaction between smoking and TLR2 ?22 with risk of gastric cancer. PMID- 26880586 TI - Transcriptomic changes associated with DKK4 overexpression in pancreatic cancer cells detected by RNA-Seq. AB - The promotion of tumor development by Dickkopf 4 (DKK4) is receiving increased attention. However, the association between DKK4 and pancreatic cancer remains unclear. DKK4 expression was measured in pancreatic ductal adenocarcinoma tissues using qRT-PCR and immunohistochemistry. A DKK4-overexpressing pancreatic cancer cell line was established, and the differentially expressed genes (DEGs) that were induced by DKK4 were identified using transcriptome sequencing. The association between the identified DEGs and pancreatic cancer was assessed using gene ontology (GO), pathway analysis, pathway interaction networks, differentially expressed gene interaction network analysis, and co-expression gene networks. Finally, the accuracy of the analyses was validated using serial paraffin and frozen sections of clinical samples. DKK4 is highly expressed in pancreatic cancer tissues. DEGs of overexpression DKK4 of PANC-1 are mostly upregulated. GO and pathway analysis showed that DKK4 are associated with tumor and organ development and immune inflammation. The mitogen-activated protein kinase (MAPK) signaling pathway was the main signal transduction pathway that showed significant enrichment in overexpression DKK4 of PANC-1. The results of GO, pathway analyses, and differentially expressed gene interaction network identified genes that are closely associated with tumor development, including MAPK3, PIK3R3, VAV3, JAG1, and Notch3. The immunohistochemistry and immunofluorescence results suggested that DKK4 is co-expressed with MAPK3 and VAV3 in pancreatic cancer tissues. The results presented here show for the first time that DKK4 is highly expressed in pancreatic cancer tissues. Bioinformatics analysis of a DKK4-overexpressing of PANC-1 identified several oncogenes that are closely associated with tumors, and the MAPK signaling pathway is the core signal transduction pathway. DKK4 can be co-expressed with MAPK3 and VAV3 in pancreatic ductal adenocarcinoma tissues. Thus, DKK4 may have function on the development and progression of pancreatic cancer. PMID- 26880587 TI - The interplay between microRNAs and Twist1 transcription factor: a systematic review. AB - Twist1 (also known as Twist) is a transcription factor that belongs to the family of basic helix-loop-helix (bHLH) proteins. It functions as a negative regulator of epithelial gene expression and a positive regulator of mesenchymal gene expression, thereby leading to induction of the epithelial mesenchymal transition (EMT), a process in which epithelial cells acquire the motile and migratory characteristics of mesenchymal cells. In addition to regulating the expression of protein-coding genes, Twist1 regulates the expression of microRNAs (miRNAs), adding a regulatory layer to EMT induction. Interestingly, the mRNA of Twist1 represents a downstream target of miRNAs, indicating an intricate network between miRNAs and Twist1. This network was shown to play multiple roles in cancer cell migration, invasion, and metastasis. The network can induce angiogenesis, protect cells from oncogene-induced apoptosis and senescence, enhance cancer cell resistance to conventional therapies, and increase cancer stem cell (CSC) populations. Recently, miRNAs have attracted considerable attention as potential promising tools in cancer therapies. Thus, this systematic review was conducted to clarify the reciprocal link between Twist1 and miRNAs in order to provide potential candidate miRNAs for diagnostic and therapeutic approaches in cancer treatment. PMID- 26880588 TI - Comparison of in vitro antileukemic activity of obatoclax and ABT-737. AB - Obatoclax and ABT-737 belong to a new class of anticancer agents known as BH3 mimetics. These agents antagonize the anti-apoptotic members of Bcl-2 family. The Bcl-2 proteins modulate sensitivity of many types of cancer cells to chemotherapy. Therefore, the objective of the present study was to examine and compare the antileukemic activity of obatoclax and ABT-737 applied alone, and in combination with anticancer agent, mafosfamide and daunorubicin. The in vitro cytotoxic effects of the tested agents on human leukemia cells were determined using the spectrophotometric MTT test, Coulter electrical impedance method, flow cytometry annexin V-fluorescein/propidium iodide assay, and light microscopy technique. The combination index analysis was used to quantify the extent of agent interactions. BH3 mimetics significantly decreased the leukemia cell viability and synergistically enhanced the cytotoxic effects induced by mafosfamide and daunorubicin. Obatoclax affected the cell viability to a greater degree than did ABT-737. In addition, various patterns of temporary changes in the cell volume and count, and in the frequency of leukemia cells undergoing apoptosis, were found 24 and 48 h after the tested agent application. ABT-737 combined with anticancer agents induced apoptosis more effectively than obatoclax when given in the same combination regimen. The results of the present study point to the different antileukemic activities of obatoclax and ABT-737, when applied alone, and in combination with anticancer agents. A better understanding of the exact mechanisms of BH3 mimetic action is of key importance for their optional use in cancer therapy. PMID- 26880589 TI - Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation. AB - BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 +/- 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 +/- 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 +/- 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 +/- 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients. PMID- 26880590 TI - An integrative approach to phylogeny reveals patterns of environmental distribution and novel evolutionary relationships in a major group of ciliates. AB - Peritrichs are a major group of ciliates with worldwide distribution. Yet, its internal phylogeny remains unresolved owing to limited sampling. Additionally, ecological distributions of peritrichs are poorly known. We performed substantially expanded phylogenetic analyses of peritrichs that incorporated SSU rDNA sequences of samples collected from three continents, revealing a number of new relationships between and within major lineages that greatly challenged the classic view of the group. Interrogation of a dataset comprising new environmental sequences from an estuary and the open ocean generated with high throughput sequencing and clone libraries plus putative environmental peritrich sequences at Genbank, produced a comprehensive tree of peritrichs from a variety of habitats and revealed unique ecological distribution patterns of several lineages for the first time. Also, evidence of adaptation to extreme environments in the Astylozoidae clade greatly broadened the phylogenetic range of peritrichs capable of living in extreme environments. Reconstruction of ancestral states revealed that peritrichs may have transitioned repeatedly from freshwater to brackish/marine/hypersaline environments. This work establishes a phylogenetic framework for more mature investigations of peritrichs in the future, and the approach used here provides a model of how to elucidate evolution in the context of ecological niches in any lineage of microbial eukaryotes. PMID- 26880591 TI - Microwave-assisted Synthesis and antifungal activity of coumarin[8,7 e][1,3]oxazine derivatives. AB - The synthesis of novel coumarin[8,7-e][1,3]oxazine derivatives through a microwave-assisted three-component one-pot Mannich reaction is described in this study. All the target compounds were evaluated in vitro for their antifungal activity against Botrytis cinerea, Colletotrichum capsici, Alternaria solani, Gibberella zeae, Rhizoctonia solani, and Alternaria mali. The preliminary bioassays showed that 5e, 5m, and 5s exhibited good antifungal activity and the most active compound was 5m with an [Formula: see text] value as low as 2.1 nM against Botrytis cinerea. PMID- 26880592 TI - New psychoactive substance use among regular psychostimulant users in Australia, 2010-2015. AB - OBJECTIVE: To examine the rates and patterns of new psychoactive substance (NPS) use amongst regular psychostimulant users (RPU) in Australia. METHOD: Data were obtained from the 2010-2015 Ecstasy and related Drugs Reporting System (EDRS), which comprised a total cross-sectional sample of 4122RPU. RESULTS: Recent use of 'any' NPS increased from 33% in 2010 to 40% in 2015, although trends of use differed significantly across NPS classes. The correlates associated with NPS use also varied across NPS classes: frequent (i.e. weekly or more) ecstasy users were more likely to report recent phenethylamine use; LSD users were more likely to report recent phenethylamine and tryptamine use; and daily cannabis users were more likely to report recent synthetic cannabinoid use than RPU who had not used NPS. 'Poly' NPS consumers were found to be a particularly high risk group and were significantly more likely to be younger, male, report daily cannabis use, report weekly or more ecstasy use, report recent LSD use, have higher levels of poly drug use, have overdosed on any drug in the past year, and to have engaged in past month criminal activity. CONCLUSION: NPS use has been established as a significant and ongoing practice amongst our sample of RPU. It appears that RPU seek out NPS with similar properties to the illicit drugs that they are already consuming, with poly NPS consumers found to be a particularly high risk group. PMID- 26880593 TI - Interviewer-administered TLFB vs. self-administered computerized (A-CASI) drug use frequency questions: a comparison in HIV-infected drug users. AB - BACKGROUND: Substance use can have major consequences among HIV patients. Interviewer- or self-administered modalities are widely used to measure drug use frequency. This often involves Timeline Follow-Back (TLFB) interviewer administered measures, or self-administered computerized questions assessing similar information via Audio Computer-Assisted Self Interview (A-CASI). Little is known about agreement between these two modalities on drug use frequency in HIV-infected samples. METHODS: Prior to randomization into a trial of brief interventions to reduce drug use, 240 HIV patients completed a baseline A-CASI assessment battery that included questions on drug use frequency, followed by an interviewer-administered TLFB. Each measure generated number of days patients used their primary drug in the prior 30 days. Agreement between TLFB and A-CASI modalities on days using primary drug was determined using intraclass correlation coefficients (ICC). Regression analysis tested the association of patient characteristics with discrepancies between TLFB and A-CASI modalities. RESULTS: Overall agreement was excellent (ICC=.80), with little variation by primary drug, education, race, current drug treatment, binge drinking or years since HIV diagnosis. Gender, ethnicity (Hispanic vs. non-Hispanic) and age predicted differences in days used (p<0.05); the A-CASI modality reflected more days used than TLFB. CONCLUSIONS: Measures of days used primary drug showed high agreement whether assessed by interviewer-administered TLFB or by questions self administered via the A-CASI modality. Differences by gender, ethnicity and age suggest some caution in using the TLFB, although additional studies are needed. However, findings generally indicate that studies based on one assessment method or the other can be compared with reasonable confidence. PMID- 26880594 TI - Cost-effectiveness of an internet-delivered treatment for substance abuse: Data from a multisite randomized controlled trial. AB - BACKGROUND: Substance misuse and excessive alcohol consumption are major public health issues. Internet-based interventions for substance use disorders (SUDs) are a relatively new method for addressing barriers to access and supplementing existing care. This study examines cost-effectiveness in a multisite, randomized trial of an internet-based version of the community reinforcement approach (CRA) with contingency management (CM) known as the Therapeutic Education System (TES). METHODS: Economic evaluation of the 12-week trial with follow-up at 24 and 36 weeks. 507 individuals who were seeking therapy for alcohol or other substance use disorders at 10 outpatient community-based treatment programs were recruited and randomized to either treatment as usual (TAU) or TES+TAU. Sub-analyses were completed on participants with a poorer prognosis (i.e., those not abstinent at study entry). RESULTS: From the provider's perspective, TES+TAU as it was implemented in this study costs $278 (SE=87) more than TAU alone after 12 weeks. The quality-adjusted life years gained by TES+TAU and TAU were similar; however, TES+TAU has at least a 95% chance of being considered cost-effective for providers and payers with willingness-to-pay thresholds as low as $20,000 per abstinent year. Findings for the subgroup not abstinent at study entry are slightly more favorable. CONCLUSIONS: With regard to the clinical outcome of abstinence, our cost-effectiveness findings of TES+TAU compare favorably to those found elsewhere in the CM literature. The analyses performed here serve as an initial economic framework for future studies integrating technology into SUD therapy. PMID- 26880597 TI - Assignment of absolute stereostructures through quantum mechanics electronic and vibrational circular dichroism calculations. AB - Elucidation of absolute configuration of chiral molecules including structurally complex natural products remains a challenging problem in organic chemistry. A reliable method for assigning the absolute stereostructure is to combine the experimental circular dichroism (CD) techniques such as electronic and vibrational CD (ECD and VCD), with quantum mechanics (QM) ECD and VCD calculations. The traditional QM methods as well as their continuing developments make them more applicable with accuracy. Taking some chiral natural products with diverse conformations as examples, this review describes the basic concepts and new developments of QM approaches for ECD and VCD calculations in solution and solid states. PMID- 26880596 TI - An ultrasensitive label-free electrochemical immunosensor based on signal amplification strategy of multifunctional magnetic graphene loaded with cadmium ions. AB - Herein, a novel and ultrasensitive label-free electrochemical immunosensor was proposed for quantitative detection of human Immunoglobulin G (IgG). The amino functionalized magnetic graphenes nanocomposites (NH2-GS-Fe3O4) were prepared to bond gold and silver core-shell nanoparticles (Au@Ag NPs) by constructing stable Au-N and Ag-N bond between Au@Ag NPs and -NH2. Subsequently, the Au@Ag/GS-Fe3O4 was applied to absorb cadmium ion (Cd(2+)) due to the large surface area, high conductivity and exceptional adsorption capability. The functional nanocomposites of gold and silver core-shell magnetic graphene loaded with cadmium ion (Au@Ag/GS Fe3O4/Cd(2+)) can not only increase the electrocatalytic activity towards hydrogen peroxide (H2O2) but also improve the effective immobilization of antibodies because of synergistic effect presented in Au@Ag/GS-Fe3O4/Cd(2+), which greatly extended the scope of detection. Under the optimal conditions, the proposed immunosensor was used for the detection of IgG with good linear relation in the range from 5 fg/mL to 50 ng/mL with a low detection limit of 2 fg/mL (S/N = 3). Furthermore, the proposed immunosensor showed high sensitivity, special selectivity and long-term stability, which had promising application in bioassay analysis. PMID- 26880595 TI - Emotion dysregulation and amygdala dopamine D2-type receptor availability in methamphetamine users. AB - BACKGROUND: Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala. METHOD: Ninety-four methamphetamine-using and 102 healthy-control subjects completed the Difficulties in Emotion Regulation Scale (DERS); 33 of those who used methamphetamine completed the Addiction Severity Index (ASI). A subset of 27 methamphetamine-group and 20 control-group subjects completed positron emission tomography with [(18)F]fallypride to assay amygdala D2-type dopamine receptor availability, measured as binding potential (BPND). RESULTS: The methamphetamine group scored higher than the control group on the DERS total score (p<0.001), with DERS total score positively correlated with the Drug Composite Score on the ASI (p=0.02) in the methamphetamine group. The DERS total score was positively correlated with amygdala BPND in both groups and the combined group of participants (combined: r=0.331, p=0.02), and the groups did not differ in this relationship. CONCLUSION: These findings highlight problems with emotion regulation linked to methamphetamine use, possibly contributing to personal and interpersonal behavioral problems. They also suggest that D2-type dopamine receptors in the amygdala contribute to emotion regulation in both healthy and methamphetamine-using subjects. PMID- 26880598 TI - Marine natural products sourced from marine-derived Penicillium fungi. AB - Marine micro-organisms have been proven to be a major source of marine natural products (MNPs) in recent years, in which filamentous fungi are a vital source of bioactive natural products for their large metagenomes and more complex genetic backgrounds. This review highlights the 390 new MNPs from marine-derived Penicillium fungi during 1991 to 2014. These new MNPs are categorized based on the environment sources of the fungal hosts and their bioactivities are summarized. PMID- 26880599 TI - Elderly people as "apocalyptic demography"? A study of the life stories of older people in Hong Kong born in the 1930s. AB - In Hong Kong, the general view still follows the biomedical discourse to define aging. The government and leading gerontologists follow the prevailing representation of elderly and describe growing old as a process of becoming "frail, infirm, and vulnerable" (Fealy et al., 2012: 91). Discussions of demographic trends often focus on the drastic effects of an aging society on economic development. Our research indicates that Hong Kong's construction of aging is a product of its market-driven economy. Drawing from the life stories of eight participants born in the 1930s, we examine the meaning of aging and the formation of character in a specific historical context, adopting the life-course perspective. We wish to understand how larger movements in the social and political world shaped the experiences of the participants and the strategies they developed to maintain agency and control in life. The participants in our study struggled for survival through unprecedented political disasters and social turmoil in their youth. When they reached maturity in the 1960s and 1970s, they devoted themselves to bettering their lives and contributed to the economic boom of the city. We maintain that the biomedical model offers a reductive and unjust means of viewing the people in this cohort, who are often seen as a problem and a burden. Challenging the prevailing ageist attitude, we set the life stories of the participants against the dominant biomedical model of aging. Our work aims to establish a just description of the life experiences of Hong Kong people. PMID- 26880600 TI - The complexities of female aging: Four women protagonists in Penelope Lively's novels. AB - Penelope Lively is a well-known contemporary British author who has published a good number of novels and short stories since she started her literary career in her late thirties. In her novels, Lively looks at the lives of contemporary characters moulded by specific historical as well as cultural circumstances. Four of her novels, published from 1987 to 2004, present middle-aged and older women as their main protagonists. Through the voices and thoughts of these female characters, the reader is presented with a multiplicity of realities in which women find themselves after their mid-fifties within a contemporary context. Being a woman and entering into old age is a double-sided jeopardy which has increasingly been present in contemporary fiction. Scholars such as Simone de Beauvoir (1949) and Susan Sontag (1972) were among the first to point out a "double standard of aging" when they assured that women were punished when showing external signs of aging much sooner than men. In Lively's four novels, the aging protagonists present their own stories and, through them, as well as through the voices of those around them, the reader is invited to go beyond the aging appearance of the female protagonists while challenging the limiting conceptions attached to the old body and, by extension, to the social and cultural overtones associated with old age. PMID- 26880601 TI - The meaningfulness of time; Narratives of cancer among chronically ill older adults. AB - This study, using ethnographically-based interviews, sought to describe how chronically ill older adults experience a new cancer diagnosis and the effects of this on their interpretations of personal health, aging, and the future. Three semi-structured interviews were conducted with each of the fifteen informants. We asked questions that explored each individual's life history, chronic illness occurrence, and direct experiences with cancer. Interviews were structured to provide social and historical contexts to enhance our understanding of the informants' illness narratives. Interview transcripts were analyzed thematically to describe how individuals described the cancer experience, its meaning, and its consequences. One of the major findings of our study was the role of cancer in disrupting individual biography, an interruption that fragmented time into three distinct segments: the Recalled Past, the Existent Present, and the Imagined Future. We highlight three main themes around the experience of illness-related time: (1) disruption found in individual biographical accounts as a result of fragmented time dimensions; (2) altered projections of a continuous sense of self into the future; and (3) modified treatment decisions resulting from a perceived altered life course and the finitude of advancing age. We further introduce the concept of Anomalous Time as a permutation of time central to individual experiences of cancer. Implications for how older adults understood their cancer and individual reactions relevant to seeking care are discussed. PMID- 26880602 TI - 'Nobody would say that it is Alzheimer's or dementia at this age': Family adjustment following a diagnosis of early-onset dementia. AB - OBJECTIVES: Family interaction and intergenerational dynamics have been known to influence the efficacy of therapeutic interventions and as such, the understanding of such dynamics in the experience of transitions can assist in strengthening the support provided to families living with such diagnoses. As such, the aims and objectives of this work were to develop a deeper understanding of family transition in early-onset dementia and to construct a representative model of this experience. METHOD: This qualitative study used an 'initial-and follow-up' interview design with semi-structured in-depth interviews in participants' homes. A framework approach to qualitative data analysis was used in order to identify important points of transition in the family experience of early-onset dementia and how families frame and respond to their own health expectations. RESULTS: Nine families provided written informed consent to participate in the study. The nine participating families were made up of 20 participants, including nine spousal pairs and two young adult children. Each family participated in two research interviews in their individual homes. Four major themes emerged from the data: Diagnosis; Finances; Relationships; and Meaningful Activity. CONCLUSION: Transitions experienced by families in early onset dementia can be significantly impacted by the opportunity and availability of meaningful activity and/or a purposeful role. Not only does this activity benefit both the person with dementia and their family, but also supports much needed home and community living for people with dementia, as demonstrated by predicted future bed shortages in Canadian hospitals and long term care facilities. PMID- 26880603 TI - Aging embodiment and the somatic work of getting into and out of a car. AB - This study examines the embodied realities and sensory experience of vehicle ingress and egress from the point of view of older drivers. In-depth interviews were conducted with 15 women and three men, aged 57-81, and followed by ride-a longs whereby the researcher observed participants in interaction with their automobile. Using the perspective of phenomenological gerontology and the concept of somatic work (Vannini, Waskul, & Gottschalk, 2012), older drivers are conceptualized as simultaneously sensing and making sense of somatic experience evoked by aging embodiment and the bodily movements required of entry and exit into an automobile. It is argued that older drivers acquire a sensory auto biography of incorporated bodily memory regarding vehicle morphology and texture in their past and current life, which informs embodied capacities of movement, awareness, and response relative to practical knowledge about what is attainable (or unattainable) for a sensuous older body. Through reflective and reflexive engagement with the sensory realm and material world, participants report structuring their lives through the haptics of touch, adoption of somatic rules, consumerist practices, as well as, specialized bodily movements and footwork sequences to ensure safety and comfort when using their automobile. PMID- 26880605 TI - No more lock-step retirement: Boomers' shifting meanings of work and retirement. AB - Standard pathways for work and retirement are being transformed as the large Boomer cohort moves through typical retirement ages during a moment of economic, social and political change. People are delaying retirement and moving into and out of paid work as the standard lock-step retirement becomes less dominant. However, little research has explored how and why Boomers are taking on these diverse pathways in their later careers. Accordingly, we conduct in-depth interviews with working and retired white-collar Boomers, exploring how they are working and the meanings and motivations for their decisions and plans in their later careers. We find that there is no single dominant pattern for retirement, but rather a diverse mix of pathways shaped by occupational identities, finances, health and perceptions of retirement. Boomers express a desire to have control over their time and to find meaning and purpose in either paid or unpaid activities. However, life course transitions, normative cultural scripts, and gender and class locations as well as workplace and social policies constrain their decisions and plans. PMID- 26880604 TI - Aging bodies and desistance from crime: Insights from the life stories of offenders. AB - The processes involved in the transition from crime to desistance, in relation to how those involved in criminal activity give meaning to their experiences of aging over time, has received little empirical scrutiny in the criminological literature. In this article, we unpack and flesh out the multiple meanings of age by drawing on a life story study of desistance from crime. Our analysis foregrounds the following key themes and the interactive parts they play in the process of desistence: general perceptions of aging (critical ages and the ambiguity of age); the significance of the aging body (crime as a young person's game, tiredness, and slowing down); age and risk assessment; and feelings of missing out and lost time with age. We conclude by suggesting that researchers into the phenomenon of desistance with an interest in maturation theory might benefit from integrating work undertaken in the sociology of embodiment and critical gerontology. A brief example of how this integration might operate is provided. PMID- 26880606 TI - Measuring the size dependence of thermal conductivity of suspended graphene disks using null-point scanning thermal microscopy. AB - Using null-point scanning thermal microscopy (NP SThM), we have measured and analyzed the size dependence of the thermal conductivity of graphene. To do so, we rigorously re-derived the principal equation of NP SThM in terms of thermal property measurements so as to explain how this technique can be effectively used to quantitatively measure the local thermal resistance with nanoscale spatial resolution. This technique has already been proven to resolve the major problems of conventional SThM, and to quantitatively measure the temperature profile. Using NP SThM, we measured the variation in the thermal resistance of suspended chemical vapor deposition (CVD)-grown graphene disks with radii of 50-3680 nm from the center to the edge with respect to the size. By thoroughly analyzing the size dependence of the thermal resistance, we show that, with increasing graphene size, the ballistic resistance becomes more dominant in the thermal resistance experienced by a heat source of finite size and that the thermal conductivity experienced by such a heat source can even decrease. The results of this study reveal that the thermal conductivity of graphene detected by a heat source depends on the size of the heat source relative to that of the suspended graphene and on how the heat source and graphene are connected. As demonstrated in this study, NP SThM will be very useful for quantitative thermal characterization of not only CVD-grown graphene but also various other nanomaterials and nanodevices. PMID- 26880607 TI - Maternal exposure to carbon monoxide and fine particulate matter during pregnancy in an urban Tanzanian cohort. AB - Low birthweight contributes to as many as 60% of all neonatal deaths; exposure during pregnancy to household air pollution has been implicated as a risk factor. Between 2011 and 2013, we measured personal exposures to carbon monoxide (CO) and fine particulate matter (PM2.5 ) in 239 pregnant women in Dar es Salaam, Tanzania. CO and PM2.5 exposures during pregnancy were moderately high (geometric means 2.0 ppm and 40.5 MUg/m3 ); 87% of PM2.5 measurements exceeded WHO air quality guidelines. Median and high (75th centile) CO exposures were increased for those cooking with charcoal and kerosene versus kerosene alone in quantile regression. High PM2.5 exposures were increased with charcoal use. Outdoor cooking reduced median PM2.5 exposures. For PM2.5 , we observed a 0.15 kg reduction in birthweight per interquartile increase in exposure (23.0 MUg/m3 ) in multivariable linear regression; this finding was of borderline statistical significance (95% confidence interval 0.30, 0.00 kg; P = 0.05). PM2.5 was not significantly associated with birth length or head circumference nor were CO exposures associated with newborn anthropometrics. Our findings contribute to the evidence that exposure to household air pollution, and specifically fine particulate matter, may adversely affect birthweight. PMID- 26880608 TI - MULTIDETECTOR COMPUTED TOMOGRAPHIC AND LOW-FIELD MAGNETIC RESONANCE IMAGING ANATOMY OF THE QUADRIGEMINAL CISTERN AND CHARACTERIZATION OF SUPRACOLLICULAR FLUID ACCUMULATIONS IN DOGS. AB - Focal fluid accumulations in the supracollicular region are commonly termed quadrigeminal cysts and may be either subclinical or associated with neurologic deficits in dogs. Little published information is available on normal imaging anatomy and anatomic relationships for the canine quadrigeminal cistern. Objectives of this observational, cross-sectional study were to describe normal quadrigeminal cistern anatomy and determine the prevalence and characteristics of supracollicular fluid accumulations in dogs. Normal descriptions were accomplished using computed tomographic (CT) cisternography in one canine cadaver, and CT and magnetic resonance imaging (MRI) studies of the brain in four prospectively recruited dogs with no evidence of intracranial disease. Prevalence and characteristics descriptions were accomplished using a retrospective review of brain CT or MRI studies performed during the period of 2005-2015. The normal quadrigeminal cistern consistently exhibited a complex H shape and was separated from the third ventricle by a thin membrane. Prevalence of supracollicular fluid accumulations (SFAs) was 2.19% among CT studies (n = 4427) and 2.2% among MRI studies (n = 626). Dogs with SFA were significantly younger than control dogs (P < 0.0001). Shih-tzu (OR = 111.6), Chihuahua (OR = 81.1), and Maltese (OR = 27.6) breed dogs were predisposed (P < 0.0001). Among dogs with SFAs, the following three patterns were defined: (1) third ventricle (49.54%), (2) quadrigeminal cistern (13.51%), and (3) both third ventricle and quadrigeminal cistern (36.93%). Authors recommend that the term supracollicular fluid accumulation (SFA) should be used rather than the term quadrigeminal cyst to describe these focal fluid accumulations in dogs. PMID- 26880610 TI - Microsatellite Instability as a Biomarker for PD-1 Blockade. AB - Initial results by Le and colleagues, which were published in the June 25, 2015 issue of the New England Journal of Medicine, report significant responses of cancers with microsatellite instability (MSI) to anti-PD-1 inhibitors in patients who failed conventional therapy. This finding fits into a broader body of research associating somatic hypermutation and neoepitope formation with response to immunotherapy, with the added benefit of relying on a simple, widely used diagnostic test. This review surveys the pathogenesis and prognostic value of MSI, diagnostic guidelines for detecting it, and the frequency of MSI across tumors, with the goal of providing a reference for its use as a biomarker for PD 1 blockade. MSI usually arises from either germline mutations in components of the mismatch repair (MMR) machinery (MSH2, MSH6, MLH1, PMS2) in patients with Lynch syndrome or somatic hypermethylation of the MLH1 promoter. The result is a cancer with a 10- to 100-fold increase in mutations, associated in the colon with poor differentiation, an intense lymphocytic infiltrate, and a superior prognosis. Diagnostic approaches have evolved since the early 1990s, from relying exclusively on clinical criteria to incorporating pathologic features, PCR-based MSI testing, and immunohistochemistry for loss of MMR component expression. Tumor types can be grouped into categories based on the frequency of MSI, from colorectal (20%) and endometrial (22%-33%) to cervical (8%) and esophageal (7%) to skin and breast cancers (0%-2%). If initial results are validated, MSI testing could have an expanded role as a tool in the armamentarium of precision medicine. PMID- 26880611 TI - Does Recognition of Meaning in Life Confer Resiliency to Suicide Ideation Among Community-Residing Older Adults? A Longitudinal Investigation. AB - OBJECTIVE: To test a theoretical model of the onset and/or exacerbation of late life suicide ideation, incorporating consideration of risk, resiliency, and precipitating factors. DESIGN: A longitudinal study investigating whether recognition of meaning in life (MIL) at baseline confers resiliency to the onset and/or exacerbation of suicide ideation over a 6- to 22-month period of follow up, controlling for baseline depression, self-rated health, and physical functioning, and for frequency and intensity of intervening daily hassles. SETTING: Mental health research offices in an urban academic health sciences center. PARTICIPANTS: 173 community-residing older adults (mean: 73.9 years, SD: 6.1 years, range: 65-93 years) recruited from health, wellness, and interest programs, and from newspaper ads and flyers posted in London, Ontario, a mid sized Canadian city. A total of 126 (73%) completed follow-up assessments. MEASUREMENTS: Participants completed a demographics form, a cognitive screen, and measures of suicide ideation and of risk (depressive symptom severity, self-rated health problems, and physical functioning) and potential resiliency (recognition of MIL) factors at baseline and follow-up assessment points, and a measure of intervening daily hassles. RESULTS: MIL at baseline was negatively associated with the onset and/or exacerbation of suicide ideation over time, controlling for risk factors and intervening precipitating factors. The extent and relative significance of this finding differed with the manner in which MIL and suicide ideation were operationalized. CONCLUSIONS: Study findings add to a growing body of knowledge suggesting that MIL may play an important role in promoting mental health and well-being and potentially conferring resiliency to contemplations of suicide in later life. PMID- 26880612 TI - Age Differences in the Association of Social Support and Mental Health in Male U.S. Veterans: Results From the National Health and Resilience in Veterans Study. AB - OBJECTIVE: To examine the associations between multiple aspects of social support perceived support, structural support, and community integration-and mental health difficulties in younger and older male veterans. Drawing from Socioemotional Selectivity Theory (SST), we hypothesized that greater support would be more strongly negatively related to mental health difficulties in older than younger veterans. DESIGN: Cross-sectional Web survey of younger and older male veterans recruited from a contemporary, nationally representative sample of veterans residing in the United States. SETTING: Data were drawn from the National Health and Resilience in Veterans Study. PARTICIPANTS: Participants were 290 younger male veterans (mean age: 37.0 years, SD: 6.9, range: 21-46) and 326 older male veterans (mean age: 81.7 years, SD: 3.2, range: 78-96). MEASUREMENTS: Participants completed measures of sociodemographic and military characteristics, perceived and structural social support, community integration, and mental health difficulties. RESULTS: In contrast to SST, higher perceived support was associated with fewer mental health difficulties in younger but not older veterans. In line with SST, community integration was associated with fewer mental health difficulties in older but not younger veterans. Structural support was not associated with mental health difficulties in either group. CONCLUSION: Results of this study provide mixed support for SST and suggest that different aspects of social support may help promote the mental health of younger and older male U.S. veterans. Promotion of community engagement may help promote mental health in older veterans, whereas promotion of functional social support may help promote mental health in younger veterans. PMID- 26880613 TI - Prevalence, Correlates, and Treatment of Mental Disorders among Lebanese Older Adults: A National Study. AB - OBJECTIVES: Data on the mental health of older adults in the Middle East is lacking. Prevalence of mental disorders in Lebanese older adults (age: 60+ years) as well as accounts of their attitude towards seeking professional help for mental disorders were investigated. The results of older adults were compared to a younger age group (18-59 years). DESIGN: Cross-sectional nationally representative study, using data from the Lebanese Evaluation of the Burden of Ailments and Needs of the Nation. SETTING: Community-based epidemiologic survey. PARTICIPANTS: Community-dwelling adults (N = 2,857) in Lebanon. MEASUREMENTS: Mental disorders were evaluated using the World Health Organization Composite International Diagnostic Interview. RESULTS: The lifetime and 12-month prevalences of having "any mental disorder" in older adults (N = 593) were 17.4% and 10.6%, respectively, and were significantly lower than the prevalence in younger adults (25.7% and 18.5%, respectively). Female sex, low household income, social disability, and exposure to war trauma were significant correlates of 12 month mental disorders in older adults. Of those with a 12-month mental disorder, 16.0% sought professional help for their condition in the past year. CONCLUSIONS: As shown in other epidemiologic studies, the prevalence of mental disorders in Lebanon was lower in older adults as compared to younger adults. Several factors in epidemiologic studies, however, may contribute to the underdiagnosis of mental disorders in older adults. No significant differences in attitude towards mental health services were found between older and younger age groups. The importance of interventions that improve the social relationships of older adults is highlighted. PMID- 26880614 TI - Letter to the Editor. PMID- 26880617 TI - Species selection and random drift in macroevolution. AB - Species selection resulting from trait-dependent speciation and extinction is increasingly recognized as an important mechanism of phenotypic macroevolution. However, the recent bloom in statistical methods quantifying this process faces a scarcity of dynamical theory for their interpretation, notably regarding the relative contributions of deterministic versus stochastic evolutionary forces. I use simple diffusion approximations of birth-death processes to investigate how the expected and random components of macroevolutionary change depend on phenotype-dependent speciation and extinction rates, as can be estimated empirically. I show that the species selection coefficient for a binary trait, and selection differential for a quantitative trait, depend not only on differences in net diversification rates (speciation minus extinction), but also on differences in species turnover rates (speciation plus extinction), especially in small clades. The randomness in speciation and extinction events also produces a species-level equivalent to random genetic drift, which is stronger for higher turnover rates. I then show how microevolutionary processes including mutation, organismic selection, and random genetic drift cause state transitions at the species level, allowing comparison of evolutionary forces across levels. A key parameter that would be needed to apply this theory is the distribution and rate of origination of new optimum phenotypes along a phylogeny. PMID- 26880615 TI - Carbon dioxide-mediated vasomotion of extra-cranial cerebral arteries in humans: a role for prostaglandins? AB - KEY POINTS: Cerebral blood flow increases during hypercapnia and decreases during hypocapnia; it is unknown if vasomotion of the internal carotid artery is implicated in these responses. Indomethacin, a non-selective cyclooxygenase inhibitor (used to inhibit prostaglandin synthesis), has a unique ability to blunt cerebrovascular carbon dioxide reactivity, while other cyclooxygenase inhibitors have no effect. We show significant dilatation and constriction of the internal carotid artery during hypercapnia and hypocapnia, respectively. Indomethacin, but not ketorolac or naproxen, reduced the dilatatory response of the internal carotid artery to hypercapnia The differential effect of indomethacin compared to ketorolac and naproxen suggests that indomethacin inhibits vasomotion of the internal carotid artery independent of prostaglandin synthesis inhibition. ABSTRACT: Extra-cranial cerebral blood vessels are implicated in the regulation of cerebral blood flow during changes in arterial CO2 ; however, the mechanisms governing CO2 -mediated vasomotion of these vessels in humans remain unclear. We determined if cyclooxygenase inhibition with indomethacin (INDO) reduces the vasomotor response of the internal carotid artery (ICA) to changes in end-tidal CO2 (P ETC O2). Using a randomized single-blinded placebo-controlled study, participants (n = 10) were tested on two occasions, before and 90 min following oral INDO (1.2 mg kg(-1) ) or placebo. Concurrent measurements of beat-by-beat velocity, diameter and blood flow of the ICA were made at rest and during steady-state stages (4 min) of iso-oxic hypercapnia (+3, +6, +9 mmHg P ETC O2) and hypocapnia (-3, -6, -9 mmHg P ETC O2). To examine if INDO affects ICA vasomotion independent of cyclooxygenase inhibition, two participant subsets (each n = 5) were tested before and following oral ketorolac (post 45 min, 0.25 mg kg(-1) ) or naproxen (post 90 min, 4.2 mg kg(-1) ). During pre-drug testing in the INDO trial, the ICA dilatated during hypercapnia at +6 mmHg (4.72 +/- 0.45 vs. 4.95 +/- 0.51 mm; P < 0.001) and +9 mmHg (4.72 +/- 0.45 mm vs. 5.12 +/- 0.47 mm; P < 0.001), and constricted during hypocapnia at -6 mmHg (4.95 +/- 0.33 vs. 4.88 +/- 0.27 mm; P < 0.05) and -9 mmHg (4.95 +/- 0.33 vs. 4.82 +/- 0.27 mm; P < 0.001). Following INDO, vasomotor responsiveness of the ICA to hypercapnia was reduced by 67 +/- 28% (0.045 +/- 0.015 vs. 0.015 +/- 0.012 mm mmHg P ETC O2(-1) ). There was no effect of the drug in the ketorolac and naproxen trials. We conclude that: (1) INDO markedly reduces the vasomotor response of the ICA to changes in P ETC O2; and (2) INDO may be reducing CO2 mediated vasomotion via a mechanism(s) independent of cyclooxygenase inhibition. PMID- 26880618 TI - Model reduction of the intracellular-signaling subsystem of apoptosis. AB - In recent few decades numerical treatment has become a standard tool in the system analysis and investigation of complex chemical reactions networks of reacting flows. The information about certain networks of biochemical reactions constantly increases. This leads to detailed descriptions of biochemical processes as a system of differential equations of high complexity and dimension. Nowadays methods, which are able automatically reduce the system dimension and complexity, are highly desirable. Recently several methods were developed for model reduction in combustion and chemical kinetics aiming at automatic numerical treatment and constructing the reduced system. The reduced system represents reliable description reproducing the detailed system behavior accurately enough. In this work the method of qualitative ODEs system analysis and the global quasi linearization method (GQL) for kinetic mechanism reduction of combustion models are applied to the biochemical reaction network of the apoptosis. It is shown that the original model of the apoptosis can be essentially simplified firstly by using linear system integrals (9 dimensions) of the ODEs system, secondly the results of GQL analysis reveals the possibility of a further reduction (4 dimensions). It means that the final system dimension reaches 15 compare to the original 28 without any noticeable accuracy losses. PMID- 26880616 TI - Inhibitory effects of compounds isolated from the dried branches and leaves of murta (Myrceugenia euosma) on lipid accumulation in 3T3-L1 cells. AB - As obesity is a global health concern the demand for anti-obesity drugs is high. In this study, we investigated the anti-obesity effect of the dried branches and leaves of murta (Myrceugenia euosma Legrand, Myrtaceae). A methanol extract of the dried branches and leaves of murta inhibited adipogenesis in 3T3-L1 cells. Three known flavanones-cryptostrobin (1), pinocembrin (4), and 5,7-dihydroxy-6,8 dimethylflavanone (6), and three chalcones-2',6'-dihydroxy-3'-methyl-4' methoxychalcone (2), pinostrobin chalcone (3), and 2',6'-dihydroxy-4'-methoxy 3',5'-dimethylchalcone (5) were isolated from the active fraction. Structures of these compounds were identified using various spectral data. Each of these compounds also inhibited adipogenesis in 3T3-L1 cells. In particular, compound 3 was a more potent inhibitor of triglyceride accumulation than the positive control berberine. Gene expression studies revealed that treatment of 3T3-L1 cells with 3 lowers the expression levels of CCAAT/enhancer-binding protein alpha and peroxisome proliferator activator gamma2 during adipogenesis without affecting cell viability. Treatment of 3T3-L1 cells with 3 reduced the expression levels of mRNAs encoding sterol regulatory element-binding protein 1c and several lipogenic enzymes, including fatty acid synthase and stearoyl CoA desaturase-1. These results indicate that the methanol extract and compounds isolated from the dried branches and leaves of murta exert their anti-obesity effects through the inhibition of adipogenesis. PMID- 26880619 TI - Serially peeled images of the curved surface of the face based on cross-sectional images for use in plastic surgery. PMID- 26880620 TI - Comparison of four different lasers for acne scars: Resurfacing and fractional lasers. AB - BACKGROUND: Acne scars are common and cause cosmetic problems. There is a multitude of treatment options for acne scars, including dermabrasion, chemical peeling, and fillers, but the advent of laser technology has greatly improved the treatment of acne scars. Although several laser systems are available, studies comparing their efficacy are limited. This study compares the results of treatments using resurfacing (carbon dioxide, CO2; erbium-doped yttrium aluminum garnet, Er:YAG) versus fractional (nonablative fractional laser, NAFL; ablative fractional laser, AFL) lasers. METHODS: A retrospective photographic analysis of 58 patients who underwent laser treatment for facial atrophic acne scars was performed. Clinical improvement was assessed by six blinded investigators with a scale graded from 0 to 10. Adverse events were also noted. RESULTS: Mean improvement scores of the CO2, Er:YAG, NAFL, and AFL groups were 6.0, 5.8, 2.2, and 5.2, respectively. The NAFL group showed a significantly lower score than the other groups. The mean number of treatments was significantly greater in the fractional laser groups than in the resurfacing laser groups. The resurfacing laser groups had a prolonged recovery period and high risk of complications. The Er:YAG laser caused less erythema or pigmentation compared to the CO2 laser. CONCLUSIONS: Although the CO2 laser, Er:YAG laser, and AFL improved the acne scars, the CO2 laser had a greater downtime. Three consecutive AFL treatments are as effective as a single treatment with resurfacing lasers, with shorter social downtime periods and less adverse effects. PMID- 26880621 TI - Considerations regarding lipofilling in patients after breast cancer. PMID- 26880622 TI - Patient physiological status at the emergency department-ward interface and emergency calls for clinical deterioration during early hospital admission. AB - AIMS: To examine the relationship between physiological status at the emergency department-ward interface and emergency calls (medical emergency team or cardiac arrest team activation) during the first 72 hours of hospital admission. BACKGROUND: Ward adverse events are related to abnormal physiology in emergency department however the relationship between physiology at the emergency department-ward interface and ward adverse events is unknown. DESIGN: Descriptive and exploratory design. METHODS: The study involved 1980 patients at three hospitals in Melbourne Australia: i) 660 randomly selected adults admitted via the emergency department to medical or surgical wards during 2012 and who had an emergency call; and ii) 1320 adults without emergency calls matched for gender, triage category, usual residence, admitting unit and age. RESULTS/FINDINGS: The median age was 78 years and 48.8% were males. The median time to the first emergency call was 18.8 hours and >=1 abnormal parameters were documented in 34.9% of patients during the last hour of ED care and 47.1% of patients during first hour of ward care. Emergency calls were significantly more common in patients with heart rate and conscious state abnormalities during the last hour of emergency care and abnormal oxygen saturation, heart rate or respiratory rate during the first hour of ward care. Medical emergency team afferent limb failure occurred in 55.3% patients with medical emergency team activation criteria during first hour of ward care. CONCLUSION: The use of physiological status at the emergency department-ward interface to guide care planning and reasons for and outcomes of medical emergency team afferent limb failure are important areas for future research. PMID- 26880623 TI - NIH peer review percentile scores are poorly predictive of grant productivity. AB - Peer review is widely used to assess grant applications so that the highest ranked applications can be funded. A number of studies have questioned the ability of peer review panels to predict the productivity of applications, but a recent analysis of grants funded by the National Institutes of Health (NIH) in the US found that the percentile scores awarded by peer review panels correlated with productivity as measured by citations of grant-supported publications. Here, based on a re-analysis of these data for the 102,740 funded grants with percentile scores of 20 or better, we report that these percentile scores are a poor discriminator of productivity. This underscores the limitations of peer review as a means of assessing grant applications in an era when typical success rates are often as low as about 10%. PMID- 26880624 TI - Direct ingestion method for enhancing production and bioavailability of resveratrol and other phytoalexins in Vitis vinifera. AB - Phytoalexins such as resveratrol and pterostilbene, produced de novo by many plant species, including grapevine (Vitis vinifera), play a role in plant defense against injury and pathogens. In human cell lines and in animal studies, phytoalexins have been shown to be highly beneficial, with protective effects against cancer, cardiovascular disease, neurodegenerative diseases, diabetes, hyperglycemia, as well as potential effects on longevity. However, in clinical studies, there are multiple factors that restrict this plethora of health benefits attributed to phytoalexins. One of these barriers is rapid metabolism in the intestines and liver. As a means to overcome this barrier, there is evidence that retaining resveratrol in the mouth for extended periods allows for higher plasma levels of resveratrol. Processing, transport or storage may cause degradation due to light and air exposure. When the berries have been picked, they may not be at their peak phytoalexin production due to lack of elicitor induction. To overcome these barriers inherent in phytoalexin production and uptake, it is proposed that berries and possibly the edible leaves be directly ingested off of a grapevine, without harvesting. In addition to the benefit of removing these barriers to potential health benefits, this method introduces a variety of known phytoalexin elicitors, in the form of plant wounding and human saliva, which may enhance the levels of phytoalexins dramatically. The combined effect of multiple phytoalexins may also play a role in enhanced health benefits. To test this hypothesis, experiments with direct ingestion would be performed, followed by testing the participants' plasma levels of resveratrol and potentially other phytoalexins. Proposed variables to be tested include: different subjects, elicitors, cultivars of grapevine, ripeness of fruit, and a range of time for the ingestion process. The potential implications include a direct means of obtaining, in clinically beneficial doses, the tremendous health benefits that have been documented for phytoalexins in vitro and in animal studies, but that have so far remained elusive in clinical studies. This study on direct ingestion may lead to alternative methods for obtaining these clinically beneficial doses. PMID- 26880625 TI - Electrical stimulation to optimize cardioprotective exosomes from cardiac stem cells. AB - Injured or ischemic cardiac tissue has limited intrinsic capacity for regeneration. While stem cell transplantation is a promising approach to stimulating cardiac repair, its success in humans has thus far been limited. Harnessing the therapeutic benefits of stem cells requires a better understanding of their mechanisms of action and methods to optimize their function. Cardiac stem cells (CSC) represent a particularly effective cellular source for cardiac repair, and pre-conditioning CSC with electrical stimulation (EleS) was demonstrated to further enhance their function, although the mechanisms are unknown. Recent studies suggest that transplanted stem cells primarily exert their effects through communicating with endogenous tissues via the release of exosomes containing cardioprotective molecules such as miRNAs, which upon uptake by recipient cells may stimulate survival, proliferation, and angiogenesis. Exosomes are also effective therapeutic agents in isolation and may provide a feasible alternative to stem cell transplantation. We hypothesize that EleS enhances CSC-mediated cardiac repair through its beneficial effects on production of cardioprotective exosomes. Moreover, we hypothesize that the beneficial effects of biventricular pacing in patients with heart failure may in part result from EleS-induced preconditioning of endogenous CSC to promote cardiac repair. With future research, our hypothesis may provide applications to optimize stem cell therapy and augment current pacing protocols, which may significantly advance the treatment of patients with heart disease. PMID- 26880626 TI - The asymmetric protein expression hypothesis - Explaining the unilaterality of HLA-B27-positive acute anterior uveitides. AB - For reasons still unclear, most HLA-B27-positive acute anterior uveitides occur unilaterally. Building upon the growing literature showing that left-right asymmetry exist at the biomolecular and at the cellular levels, we propose a new hypothesis to explain why HLA-B27-positive acute anterior uveitides tend to affect one eye selectively. We postulate that left and right uveal tissue may present quantitatively and qualitatively different proteins to the immune system, capable to trigger an autoimmune response, and that other variables, including anatomical, cellular and molecular barriers, as well as our own eye-derived immunological tolerance and immune suppressive intraocular microenvironment may also be unequally distributed, and impact differently the immune privileges of the left and right eye. These same quantitative and qualitative differences might also explain why HLA-B27-positive acute anterior uveitides can flip-flop between the left and the right eye, after the first attack. By trying to figure out why one eye is targeted by an autoimmune reaction while the other is clinically unaffected, we might be able to better understand how and why an autoimmune reaction starts. Hopefully, this will help us devise better treatments for ocular autoimmune diseases, and contribute to the management of autoinflammatory conditions with a marked asymmetric clinical presentation in other fields. PMID- 26880627 TI - Adhesive capsulitis: An age related symptom of metabolic syndrome and chronic low grade inflammation? AB - Adhesive capsulitis (AC) is very poorly understood, particularly it's underlying etiology. Obesity and metabolic syndrome, which are strongly associated with chronic low grade inflammation, are becoming increasingly understood to underlie a raft of morbid states including upper limb pain syndromes, diabetes (DM), cardiovascular disease (CVD), cancer and central nervous system dysfunction and degeneration. Notwithstanding age, two of the strongest established risk factors for AC are DM and CVD. The hypothesis argues that similar to DM and CVD, the inflammation and capsular fibrosis seen in AC is precipitated by metabolic syndrome and chronic low grade inflammation. These pathophysiological mechanisms are highly likely to be perpetuated by upregulation of pro-inflammatory cytokine production, sympathetic dominance of autonomic balance, and neuro-immune activation. The hypothesis predicts and describes how these processes may etiologically underpin and induce each sub-classification of AC. An improved understanding of the etiology of AC may lead to more accurate diagnosis, improved management, treatment outcomes, and reduce or prevent pain, disability and suffering associated with the disease. The paper follows on with a discussion of similarities between the pathophysiology of AC to general systemic inflammatory control mechanisms whereby connective tissue (CT) fibrosis is induced as a storage depot for leukocytes and chronic inflammatory cells. The potential role of hyaluronic acid (HA), the primary component of the extracellular matrix (ECM) and CT, in the pathophysiology of AC is also discussed with potential treatment implications. Lastly, a biochemical link between physical and mental health through the ECM is described and the concept of a periventricular-limbic central driver of CT dysfunction is introduced. PMID- 26880628 TI - Cortical gray matter loss in schizophrenia: Could microglia be the culprit? AB - Cortical gray matter loss in schizophrenia remains a great therapeutic difficulty. Each psychotic episode causes irreversible cortical gray matter loss, that causes the patients to never regain their previous state of functioning. Microglial cells are part of the innate immune system and their functions, among others, include phagocytosis and release of neurotrophic factors. They have a key impact on developmental and plasticity-induced removal of neuronal precursors, live-but-stressed neurons and synapses, while also stimulating synaptic growth and development. We hypothesize that microglia are the culprit for the cortical gray matter loss in schizophrenia through abnormal synaptic pruning, phagocytosis of stressed neurons and lacking neurotrophic factor release. Furthermore, we propose a research that could validate the hypotheses using serum samples of first-episode early-onset patients. By measuring the serum levels of milk fat globule-EGF factor 8 (MFG-E8), subcomponent in the classical pathway of complement activation (C1q), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6) and interleukin-10 (IL-10), we could gain an insight into the state of microglial activation during various stages of the disease. If this hypothesis is valid, new targeted drugs could be developed in order to reduce the deterioration of cortical gray matter, thereby possibly improving negative symptoms and cognitive deficits. PMID- 26880629 TI - Muscle growth across a variety of exercise modalities and intensities: Contributions of mechanical and metabolic stimuli. AB - This paper reviews the existing evidence for the potential contribution of metabolic and mechanical stimuli to muscle growth in response to a variety of exercise modalities and intensities. Recent research has demonstrated that low load resistance training can elicit comparable hypertrophy to that of high-load resistance training when each set is performed until failure. The degree of metabolic fatigue would be greater for resistance training with lower loads compared to higher loads at the point of muscle failure, which may compensate for the lower mechanical stress. This may also explain why muscle hypertrophy occurs to varying magnitudes when activities such as cycling and walking are performed. Furthermore, the application of blood flow restriction to the working muscles during these activities induces greater hypertrophy albeit at the same level of mechanical stress, which would suggest a possible contribution from metabolic stress. Thus, it is plausible that both mechanical and metabolic stimuli are primary mechanisms for muscle hypertrophy and the degree of contributions of both stimuli determines the exercise-induced muscle hypertrophy. PMID- 26880630 TI - PTH intermittent administration may be a useful therapeutic agent to avoid premature eruption of the tooth. AB - Parathyroid hormone (PTH) acts as a controller of bone remodeling and has influence on periodontal tissues. In addition to the well-established catabolic effects (activation of bone resorption) of PTH, it is recognized that the PTH intermittent administration has anabolic effects (promotion of bone formation). However, there is no information regarding the effects of the PTH intermittent administration on the eruption tooth rate. Studies have shown that tooth eruption depends on the presence of osteoclasts to create an eruption pathway through the alveolar bone. It may also be controlled by osteoblast, precursor of osteoclast, and cells of periodontal ligament. Our hypothesis is based on previous studies showing that the PTH intermittent administration can promote bone formation, particularly in the areas around which the tooth erupts. Furthermore, the PTH intermittent administration influenced periodontal ligament fiber, what may be seen as greater organization, and isomerization, as well as higher birefringence of the periodontal ligament fiber, which then offers increased resistance to the process, delaying tooth eruption. Thus, this article opens new perspectives for the treatment and maintenance of teeth that can erupt early. PMID- 26880631 TI - Dkk1: A promising molecule to connect Alzheimer's disease and osteoporosis. AB - Osteoporosis and Alzheimer's disease (AD) are the two common diseases mostly affecting persons aged over 60. Epidemiological findings revealed that osteoporosis and AD have a very high comorbidity. However, the mechanisms underlying their association are poorly understood. The Wnt signaling pathway plays a crucial role in the proper development and maintenance of brain and bone structure and function. Dickkopf-related protein 1 (Dkk1), a vital antagonist of the Wnt signaling, was reported to be closely associated with bone homeostasis and osteoporosis. Interestingly, high level of Dkk1 in the brain increases the risk of AD. It is suggested that Dkk1 may be a common potent risk factor involved in osteoporosis and AD. Therefore, we hypothesize that Dkk1 may play a role in both osteoporosis and AD. Our hypothesis will shed new light on the understanding of the relationship between these two diseases and help to explain some common characters of osteoporosis and AD. PMID- 26880632 TI - The Baby Food Hypothesis: An explanation why high fat high sugar (HFHS) mixtures are so addictive, providing novel treatment strategies to control appetite in obesity and anorexia. PMID- 26880633 TI - The low-frequency (delta and theta) oscillations model of hallucinations integrating neuronal mechanism of object representation, emotions, plasticity, memory and noise signal. PMID- 26880634 TI - Hypothesis: A single dose of an anxiolitic may prevent unnecessary visits to the emergency room during blood pressure elevations. AB - Blood pressure (BP) monitoring devices are very commonly used by the general public for self-measurement. Approximately 19% of people using these devises check their BP every day or almost every day and only one third use them because their doctor recommended it. Measurement often causes anxiety and anxiety increases blood pressure in the short term. Elderly patients often visit the emergency room (ER) due to these BP elevations. Almost 10% of patients presenting to ERs complained of high BP, and between 50-75% of them receive antihypertensive drugs (sometimes with serious adverse effects) despite the fact that only 7.5% are classified as hypertensive emergencies, and only 2.8% are at risk of serious outcome. Two studies suggested the use of anxiolitics in the treatment of excessive hypertension. When compared to captopril, treatment with diazepam or alprazolam showed to be effective in lowering BP, with no significant difference between the two groups. We therefore suggest that patients with acute elevations of BP (measured at home) try an anxiolytic before deciding to go to the ER. Patients in which BP lowers with the use of tranquilizers do not need to go to the ER. We also suggest using this strategy in patients visiting community clinics and ER for the same reason. Our hypothesis is that by using our suggestions there will be a significant reduction in the number of unnecessary visits to the ER, the use of medication that may produce serious adverse effects, and an important health cost reduction, without increasing the risk for patients (a 10% reduction of ER visits may save up to 300 million dollars/year in the US alone and prevent unnecessary use of medical facilities and manpower). PMID- 26880635 TI - ACAID as a potential therapeutic approach to modulate inflammation in neurodegenerative diseases. AB - The progressive loss of neurons and inflammation characterizes neurodegenerative diseases. Although the etiology, progression and outcome of different neurodegenerative diseases are varied, they share chronic inflammation maintained largely by central nervous system (CNS)-derived antigens recognized by T cells. Inflammation can be beneficial by recruiting immune cells to kill pathogens or to clear cell debris resulting from the primary insult. However, chronic inflammation exacerbates and perpetuates tissue damage. An increasing number of therapies that attempt to modulate neuroinflammation have been developed. However, so far none has succeeded in decreasing the secondary damage associated with chronic inflammation. A potential strategy to modulate the immune system is related to the induction of tolerance to CNS antigens. In this line, it is our hypothesis that this could be accomplished by using anterior chamber associated immune deviation (ACAID) as a strategy. Thus, we review current knowledge regarding some neurodegenerative diseases and the associated immune response that causes inflammation. In addition, we discuss further our hypothesis of the possible usefulness of ACAID as a therapeutic strategy to ameliorate damage to the CNS. PMID- 26880636 TI - Implication of immunokine profiling for cancer staging. AB - Tumor may arise from the dysregulation of immune system, which plays pivotal roles in counteracting tumor colonization, late-stage tumors, and metastases. In the midst of the establishment of cancer in vivo, immune cells are activated to release a multitude of immunokines, such as cytokines, and chemokines. Thus, since cytokine levels in tumor bearing host would be differential among local (intratumoral lesion, peritumoral normal tissue), and systemic sample site (serum), these differences might be significantly correlated to prognosis and treatment outcome for cancer patients. Previously, despite small number of patients, we demonstrated the feasibility of this proposition via only cytokine profiling. Based on this, herein we propose that immunokine profiling would be used as a surrogate, predictive tool for cancer staging, and progression. PMID- 26880637 TI - Can we find a possible structural explanation for antibody-dependent enhancement of dengue virus infection resulting in hemorrhagic fever? AB - Dengue virus infection is one of the most prevalent mosquito-borne illnesses worldwide, affecting as many as 400 million persons annually. Most people experience a self-limited viral illness, but some experience life-threatening disease. Subsequent infection with other dengue virus serotypes increases the risk of development of severe dengue disease with plasma leakage with or without hemorrhage and end organ impairment. Antibody-dependent enhancement of dengue virus infection has been implicated in the development of severe dengue disease, previously referred to as dengue hemorrhagic fever and dengue shock syndrome. We propose a structural explanation for the role of non-neutralizing antibodies in the development of antibody-dependent enhancement of dengue virus infection via complement fixation or binding to Fcgamma receptors facilitating entry into target cells. PMID- 26880638 TI - Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis). AB - Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells. PMID- 26880640 TI - The coordinated action of lecithin:retinol acyltransferase and cellular retinol binding proteins for regulation of vitamin A esterification. AB - Vitamin A is a fat-soluble vitamin required for many physiological functions. The intracellular transport of vitamin A is assisted by proteins called cellular retinol-binding proteins (CRBP I/II). The absorption, storage and usage of vitamin A are regulated by a protein called lecithin:retinol acyltransferase (LRAT), a retinol-related enzyme that transfers an acyl group derived from an sn 1 position of phosphatidylcholine to retinol. LRAT is a member of the protein family which includes HRAS-like tumor suppressors (HRASLS). However, the HRASLS proteins never use retinol as an acyl acceptor. The mechanisms underlying the different substrate specificities between LRAT and HRASLS proteins are unknown. We propose in this report that LRAT physically interacts with CRBP and the LRAT CRBP complex represents the binding pockets for both an acyl group and retinol, thus assuring the substrate specificity of LRAT. PMID- 26880639 TI - Does plasma membrane lipid composition impact the miRNA-mediated regulation of vascular inflammation? AB - BACKGROUND: Both PUFA and miRNAs are believed to be of importance in vascular diseases. On the one hand diverse nutrition societies recommend PUFA consumption to dampen inflammatory processes. On the other hand scientists intensify efforts to use miRNAs for diagnostics or therapy in context of vascular disorders. PRESENTATION OF THE HYPOTHESIS: There might be is a causal link between the plasma membrane lipid composition and the miRNA expression of monocytes and endothelial cells. PUFA enrichment of cells may affect the type and the amount of particular miRNAs produced. In this way dietary fatty acids are supposed to impact the miRNA-mediated regulation of vascular inflammatory processes. PROPOSED EXPERIMENTAL SETTING TO TEST THE HYPOTHESIS: PUFA-supplemented monocytes and endothelial cells are analyzed with respect to membrane fatty acid patterns, typical markers of vascular inflammation and miRNA expression. Experiments are performed both for undifferentiated/unstimulated as well as for differentiated/stimulated cells. Verification of identified miRNA targets is performed by means of mimics/antagomirs. IMPLICATIONS OF THE HYPOTHESIS: Innovative mechanism of action, which could point the way to a new understanding of the PUFA-mediated modulation of cellular signal transduction. If confirmed experimentally, it might stimulate vascular inflammation research and immunologic lipid science, hence, acting as source of inspiration for future therapeutic interventions in vascular diseases. PMID- 26880642 TI - Great expectations: Nutritional medicine as a mainstream in clinical psychiatry and weighing opportunities against risks. PMID- 26880641 TI - Folate deficiency affects histone methylation. AB - Formaldehyde is extremely toxic reacting with proteins to crosslinks peptide chains. Formaldehyde is a metabolic product in many enzymatic reactions and the question of how these enzymes are protected from the formaldehyde that is generated has largely remained unanswered. Early experiments from our laboratory showed that two liver mitochondrial enzymes, dimethylglycine dehydrogenase (DMGDH) and sarcosine dehydrogenase (SDH) catalyze oxidative demethylation reactions (sarcosine is a common name for monomethylglycine). The enzymatic products of these enzymes were the demethylated substrates and formaldehyde, produced from the removed methyl group. Both DMGDH and SDH contain FAD and both have tightly bound tetrahydrofolate (THF), a folate coenzyme. THF binds reversibly with formaldehyde to form 5,10-methylene-THF. At that time we showed that purified DMGDH, with tightly bound THF, reacted with formaldehyde generated during the reaction to form 5,10-methylene-THF. This effectively scavenged the formaldehyde to protect the enzyme. Recently, post-translational modifications on histone tails have been shown to be responsible for epigenetic regulation of gene expression. One of these modifications is methylation of lysine residues. The first enzyme discovered to accomplish demethylation of these modified histones was histone lysine demethylase (LSD1). LSD1 specifically removes methyl groups from di- and mono-methylated lysines at position 4 of histone 3. This enzyme contained tightly bound FAD and the products of the reaction were the demethylated lysine residue and formaldehyde. The mechanism of LSD1 demethylation is analogous to the mechanism previously postulated for DMGDH, i.e. oxidation of the N-methyl bond to the methylene imine followed by hydrolysis to generate formaldehyde. This suggested that THF might also be involved in the LSD1 reaction to scavenge the formaldehyde produced. Our hypotheses are that THF is bound to native LSD1 by analogy to DMGDH and SDH and that the bound THF serves to protect the FAD class of histone demethylases from the destructive effects of formaldehyde generation by formation of 5,10-methylene-THF. We present pilot data showing that decreased folate in livers as a result of dietary folate deficiency is associated with increased levels of methylated lysine 4 of histone 3. This can be a result of decreased LSD1 activity resulting from the decreased folate available to scavenge the formaldehyde produced at the active site caused by the folate deficiency. Because LSD1 can regulate gene expression this suggests that folate may play a more important role than simply serving as a carrier of one carbon units and be a factor in other diseases associated with low folate. PMID- 26880643 TI - Hematopoietic ontogeny and its relevance for pediatric leukemias. AB - Fetal and infant hematopoiesis display characteristics different from the adult one: our suggestion is that these features may help to explain the peculiar incidence rates of acute leukemias. Hematopoietic stem cells (HSCs) are fast cycling (those in adults instead are largely quiescent) and studies in mice demonstrated that their relative contribution to myelo- and lymphopoiesis varies during development. We hypothesize that during development some of the "hits" needed for the onset of leukemia are usually occurring (being part of the normal development), so leukemogenesis needs less mutations than in adults to take place and therefore it's more probable. The switch between the relative incidence of acute myeloid and lymphoid leukemias may be related to the changes of the percentage of lymphoid-deficient and lymphoid-proficient sub-set of HSCs during development. Further investigations may clarify this hypothesis, elucidating also the roles of the different microenvironments in determining the myeloid/lymphoid predisposition of the HSCs. PMID- 26880645 TI - Nanotrastuzumab in combination with radioimmunotherapy: Can it be a viable treatment option for patients with HER2-positive breast cancer with brain metastasis? AB - Brain metastasis of primary breast cancer (BCBM) has been rising during the last couple of decades. Approximately 25% of the patients with BCBM have a hormone receptor-negative, HER2-positive disease. Given the short life expectancy in patients with BCBM, researchers have tried many new approaches, including cesium 131(131Cs) brachytherapy, radretumab radioimmunotherapy and nanoparticles. Novel biological drug delivery techniques have successfully delivered nanobioconjugates across the blood-brain barrier (BBB). However, nanobioconjugates have significant toxicities and other drawbacks that prevent therapeutic concentrations of the active drug from being delivered to the brain lesions. Radretumab radioimmunotherapy combined with nanotrastruzumab can theoretically overcome this challenge. Radiotherapy can increase the BBB permeability, which can promote the transport and effect of nanotrastuzumab, reduce radretumab radioimmunotherapy dose and target patients with HER2-positive BCBM lesions more specifically. In this article, we propose that nanotrastuzumab in combination with radioimmunotherapy could be a viable treatment option for patients with HER2 positive breast cancer with brain metastasis. PMID- 26880644 TI - Autism: Will vitamin D supplementation during pregnancy and early childhood reduce the recurrence rate of autism in newborn siblings? AB - BACKGROUND: Vitamin D deficiency is widespread in the world including the vulnerable group of pregnant women. Vitamin D deficiency during pregnancy is hypothesized to contribute to the cause of autism. Further, it is hypothesized that vitamin D supplementation during pregnancy and early childhood will reduce the recurrence rate of autism in newborn siblings. METHODS: To investigate the hypothesis an open label prospective study was performed prescribing vitamin D during pregnancy to mothers of children with autism at a dose of 5000IU/day. The newborn siblings were at high risk for the recurrence of autism. The newborn infants were also prescribed vitamin D, 1000IU/day to their third birthday. The newborn siblings were followed for three years and during that time, were assessed for autism on two separate occasions: at 18months and 36months of age. The results were compared to the reported recurrence rates in siblings of autistic children in the literature. RESULTS: The final outcome was 1 out of 19 (5%) developed autism in contrast to the recurrence rate of approximately 20% in the literature. We did not have a control group, nor was there blinding. CONCLUSIONS: The results are promising, however, this is a preliminary study with very small numbers and was uncontrolled. Further study with larger numbers is indicated. The ethics of prescribing a low dosage of vitamin D such as 400IU D3/day to a control group of mothers in comparison to a large dose such as 5000IU D3/day are problematic in our opinion. PMID- 26880646 TI - The cubyl cation rearrangements. AB - Born-Oppenheimer molecular dynamics simulations and high-level ab initio computations predict that the cage-opening rearrangement of the cubyl cation to the 7H(+)-pentalenyl cation is feasible in the gas phase. The rate-determining step is the formation of the cuneyl cation with an activation barrier of 25.3 kcal mol(-1) at the CCSD(T)/def2-TZVP//MP2/def2-TZVP level. Thus, the cubyl cation is kinetically stable enough to be formed and trapped at moderate temperatures, but it may be rearranged at higher temperatures. PMID- 26880647 TI - Toxicogenomic analysis of the pulmonary toxic effects of hexanal in F344 rat. AB - Hexanal is a major component of indoor air pollutants and is a kind of aldehydes; it has adverse effects on human health. We performed an in vivo inhalation study and transcriptomic analysis to determine the mode of toxic actions in response to hexanal. Fischer 344 rats of both sexes were exposed by inhalation to hexanal aerosol for 4 h day-1 , 5 days week-1 for 4 weeks at 0, 600, 1000, and 1500 ppm. Throughout our microarray-based genome-wide expression analysis, we identified 56 differentially expressed genes in three doses of hexanal; among these genes, 11 genes showed dose-dependent expression patterns (10 downregulated and 1 upregulated, 1.5-fold, p < 0.05). Through a comparative toxicogenomics database (CTD) analysis of 11 genes, we determined that five genes (CCL12, DDIT4, KLF2, CEBPD, and ADH6) are linked to diverse disease categories such as cancer, respiratory tract disease, and immune system disease. These diseases were previously known for being induced by volatile organic compounds (VOCs). Our data demonstrated that the hexanal-induced dose-dependent altered genes could be valuable quantitative biomarkers to predict hexanal exposure and to perform relative risk assessments, including pulmonary toxicity. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 382-396, 2017. PMID- 26880648 TI - Can Cyclen Bind Alkali Metal Azides? A DFT Study as a Precursor to Synthesis. AB - Can cyclen (1,4,7,10-tetraazacyclododecane) bind alkali metal azides? This question is addressed by studying the geometric and electronic structures of the alkali metal azide-cyclen [M(cyclen)N3] complexes using density functional theory (DFT). The effects of adding a second cyclen ring to form the sandwich alkali metal azide-cyclen [M(cyclen)2N3] complexes are also investigated. N3(-) is found to bind to a M(+) (cyclen) template to give both end-on and side-on structures. In the end-on structures, the terminal nitrogen atom of the azide group (N1) bonds to the metal as well as to a hydrogen atom of the cyclen ring through a hydrogen bond in an end-on configuration to the cyclen ring. In the side-on structures, the N3 unit is bonded (in a side-on configuration to the cyclen ring) to the metal through the terminal nitrogen atom of the azide group (N1), and through the other terminal nitrogen atom (N3) of the azide group by a hydrogen bond to a hydrogen atom of the cyclen ring. For all the alkali metals, the N3 side-on structure is lowest in energy. Addition of a second cyclen unit to [M(cyclen)N3] to form the sandwich compounds [M(cyclen)2N3] causes the bond strength between the metal and the N3 unit to decrease. It is hoped that this computational study will be a precursor to the synthesis and experimental study of these new macrocyclic compounds; structural parameters and infrared spectra were computed, which will assist future experimental work. PMID- 26880650 TI - A mindful and unemotional revolution. PMID- 26880649 TI - Guideline-Directed Medication Use in Patients With Heart Failure With Reduced Ejection Fraction in India: American College of Cardiology's PINNACLE India Quality Improvement Program. AB - Little is known about the use of guideline-directed medical therapy (GDMT) in outpatients with heart failure with reduced left ventricular ejection fraction (HFrEF; <=40%) in India. Our objective was to understand the use of GDMT in outpatients with HFrEF in India. The Practice Innovation And Clinical Excellence (PINNACLE) India Quality Improvement Program (PIQIP) is a registry for cardiovascular quality improvement in India supported by the American College of Cardiology Foundation. Between January 2008 and September 2014, we evaluated documentation of use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers, or both, among outpatients with HFrEF seeking care in 10 centers enrolled in the PIQIP registry. Among 75 639 patients in the PIQIP registry, 34 995 had EF reported, and 15 870 had an EF <=40%. The mean age was 56 years; 23% were female. Hypertension, diabetes, coronary artery disease, and myocardial infarction were present in 37%, 23%, 27%, and 17%, respectively. Use of ACEIs/ARBs, beta-blockers, and both were documented in 33.5%, 34.9%, and 29.6% of patients, respectively. The documentation of GDMT was higher in men, in patients age >=65 years, and in those with presence of hypertension, diabetes, or coronary artery disease. Documentation of GDMT gradually increased over the study period. Among patients enrolled in the PIQIP registry, about two-thirds of patients with EF <=40% did not have documented receipt of GDMT. This study is an initial step toward improving adherence to GDMT in India and highlights the feasibility of examining quality of care in HFrEF in a resource-limited setting. PMID- 26880651 TI - Mastering mindfulness for survival in medicine. PMID- 26880652 TI - Thomas Chalmers, vitamin C and the common cold. PMID- 26880653 TI - A history of the evolution of guidelines for reporting medical research: the long road to the EQUATOR Network. PMID- 26880657 TI - The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity. AB - OBJECTIVE: Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. METHODS: Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. RESULTS: The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. CONCLUSIONS: OSA severity and its accompanying hypoxia are associated with the severity of NAFLD. PMID- 26880658 TI - Initial experience of an algorithm-based protocol for the community follow-up of men with prostate cancer. AB - OBJECTIVE: To evaluate the implementation of a novel algorithm-based discharge programme for the community follow-up of men with prostate cancer. PATIENTS AND METHODS: Men with prostate cancer considered suitable for discharge were identified from consultant-led and clinical nurse-specialist telephone clinics at Nottingham University Hospitals National Health Service Trust. Patients were discharged on to one of four discharge pathways: watchful waiting, androgen deprivation therapy (ADT), post-prostatectomy, and post-radiotherapy. Primary care providers were asked to adhere to specific surveillance measures and refer patients back to secondary care after breach of pre-defined prostate-specific antigen (PSA) level threshold criteria. Reasons for non-compliance, re-referral, and cause of death were determined for all discharged men. RESULTS: In all, 573 men were discharged across all four pathways; 169 on the watchful-waiting pathway, 229 on the ADT pathway, 95 on the post-prostatectomy pathway, and 80 on the post-radiotherapy pathway. All patients had >=12 months of follow-up. In all, 48 of 54 (88.9%) men were re-referred promptly after a PSA-threshold breach. Of the remaining six patients there were three refusals, one unrelated death before referral, and two late referrals at 4 months. Three patients were lost to follow up due to database non-registration and were subsequently recalled, none of whom had a PSA-threshold breach. There were three unexpected deaths attributed to prostate cancer: two were community deaths with no biochemical or clinical evidence of prostate cancer progression, while one was due to a likely progressive PSA non-secreting tumour. CONCLUSION: Initial results suggest the algorithm-based protocol is a viable, effective, and oncologically safe method for the controlled discharge of men from secondary to primary care. Longer-term follow-up, patient satisfaction and cost-effectiveness data are required to assess the true impact of the initiative. PMID- 26880659 TI - The role of stem cells in the prevention and treatment of radiation-induced xerostomia in patients with head and neck cancer. AB - Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation-induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow-derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study. PMID- 26880661 TI - Triphos derivatives and diphosphines as ligands in the ruthenium-catalysed alcohol amination with NH3. AB - The ruthenium-triphos and diphosphine-catalysed amination of alcohols with ammonia is reported. Various types of triphos derivatives with electron-donating functional group were synthesized and used as ligands in the Ru-catalysed alcohol amination with NH3. The triphos derivatives are effective for the formation of primary amines. On the other hand, if hemilabile diphosphines as tridentate ligands are used, mixtures of secondary-along with primary amines are obtained. It was found that even simple diphosphines can be used as ligands for the selective formation of the secondary amines. The diphosphine system allows a new entry to the Ru-catalysed formation of secondary amines. PMID- 26880660 TI - A needle in the haystack--the dire straits of needle exchange in Hungary. AB - BACKGROUND: The two largest needle exchange programs (NEPs) in Hungary were forced to close down in the second half of 2014 due to extreme political attacks and related lack of government funding. The closures occurred against a background of rapid expansion in Hungary of injectable new psychoactive substances, which are associated with very frequent injecting episodes and syringe sharing. The aim of our analysis was to predict how the overall Hungarian NEP syringe supply was affected by the closures. METHODS: We analyzed all registry data from all NEPs in Hungary for all years of standardized NEP data collection protocols currently in use (2008-2014) concerning 22 949 client enrollments, 9,211 new clients, 228,167 client contacts, 3,160,560 distributed syringes, and 2,077,676 collected syringes. RESULTS: We found that while the combined share of the two now closed NEPs decreased over time, even in their partial year 2014 they still distributed and collected about half of all syringes, and attended to over half of all clients and client contacts in Hungary. The number of distributed syringes per PWID (WHO minimum target = 100) was 81 in 2014 in Hungary, but 39 without the two now closed NEPs. CONCLUSIONS: There is a high probability that the combination of decreased NEP coverage and the increased injection risk of new psychoactive substances may lead in Hungary to a public health disaster similar to the HIV outbreaks in Romania and Greece. This can be avoided only by an immediate change in the attitude of the Hungarian government towards harm reduction. PMID- 26880662 TI - Obesity, Dietary Habits, and Sedentary Behaviors Among Adolescents in Sudan: Alarming Risk Factors for Chronic Diseases in a Poor Country. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of obesity, dietary habits, and sedentary patterns among Sudanese adolescents. METHODS: A multistage stratified sampling method was used to select 945 adolescents (507 males and 438 females) aged 14 to 18 years, from Khartoum State, Sudan. A self reported pretested questionnaire was used to collect the data. Overweight and obesity were determined using the International Obesity Task Force standard, which is based on body mass index for sex and age. RESULTS: Overweight and obesity were growing problems among urban Sudanese adolescents (10.7%). Breakfast was commonly consumed on a daily basis by the majority of adolescents (74.2%), followed by lunch (63.9%) and supper (33.5%). Snacking was not a common practice among these individuals. Vegetables (63.9%) were more frequently consumed (more than 3 days per week) than fruit (30.1%). There were significant differences between genders regarding intake of vegetables (P < .048), chicken (P < .013), dairy products, sweets, nuts, chocolate, and legumes (P < .001 for all). Sedentary behaviors (long duration of television viewing and Internet use) were highly prevalent, and physical activity was rarely practiced (6.8%). CONCLUSION: The findings indicated that risk factors for diet-related chronic diseases such as unhealthy dietary habits and sedentary behaviors are starting to rise among urban adolescents in Sudan. This creates the need for immediate action to prevent and control these risk factors before these diseases become major public health problems. PMID- 26880663 TI - Dairy and Growth, Latest Findings, and Lessons Learned. AB - BACKGROUND: Low birth weight is a significant risk factor in infant mortality and morbidity and the likelihood of chronic and clinical disease in later life. OBJECTIVE: To identify reported associations between maternal dietary patterns and risk of low birth weight offspring. METHODS: This article reviews some of the literature on this subject, with emphasis on maternal intake of dairy products. RESULTS: Published data show a positive association between maternal dairy product intake and birth weight but are inconclusive with respect to fetal length. While data are limited, 2 studies have reported a positive association between maternal consumption of milk and yogurt and birth weight, but this association is not observed with respect to consumption of cheese. CONCLUSION: If correct, by deduction, this observation is suggestive that whey protein may be a contributing factor to birth weight. Indirect evidence supporting why this observation merits further investigation is presented. PMID- 26880664 TI - Protein Quality, Growth, and Malnutrition: Advances in Science and the Role of Dairy Ingredients in Food Aid: Introduction. AB - This article is the introduction to our formal proceedings of the symposium titled "Protein Quality, Growth and Malnutrition: Latest Scientific Findings and the Role of Dairy in Food Aid," held during the Experimental Biology 2015 annual meeting in Boston, Massachusetts. PMID- 26880665 TI - Efficient MoS2 Exfoliation by Cross-beta-Amyloid Nanotubes for Multistimuli Responsive and Biodegradable Aqueous Dispersions. AB - Herein, we report the efficient exfoliation of MoS2 in aqueous medium by short cationic peptide nanotubes featuring the nucleating core (17) LVFFA(21) of beta amyloid (Abeta 1-42), a sequence associated with Alzheimer's disease. The role of morphology, length, and nature of the amyloid surface on exfoliation/dispersions of MoS2 were investigated through specific mutations of the amyloid sequences. Notably, owing to the properties of both the constituents, self-assembled soft nanostructures and MoS2 , the hybrid dispersions responded reversibly to various stimuli, including temperature, pH, and light. Addition of a protease resulted in loss of the dispersions, which are otherwise stable for months at ambient conditions. The design flexibility of the peptide sequences, along with the stimuli-responsiveness and biodegradability, can complement the applications of MoS2 in diverse fields. PMID- 26880666 TI - Visible-Light-Promoted Trifluoromethylthiolation of Styrenes by Dual Photoredox/Halide Catalysis. AB - Herein, we report a new visible-light-promoted strategy to access radical trifluoromethylthiolation reactions by combining halide and photoredox catalysis. This approach allows for the synthesis of vinyl-SCF3 compounds of relevance in pharmaceutical chemistry directly from alkenes under mild conditions with irradiation from household light sources. Furthermore, alkyl-SCF3-containing cyclic ketone and oxindole derivatives can be accessed by radical-polar crossover semi-pinacol and cyclization processes. Inexpensive halide salts play a crucial role in activating the trifluoromethylthiolating reagent towards photoredox catalysis and aid the formation of the SCF3 radical. PMID- 26880667 TI - Non-Radiative Carrier Recombination Enhanced by Two-Level Process: A First Principles Study. AB - Non-radiative recombination plays an important role in the performance of optoelectronic semiconductor devices such as solar cells and light-emitting diodes. Most textbook examples assume that the recombination process occurs through a single defect level, where one electron and one hole are captured and recombined. Based on this simple picture, conventional wisdom is that only defect levels near the center of the bandgap can be effective recombination centers. Here, we present a new two-level recombination mechanism: first, one type of carrier is captured through a defect level forming a metastable state; then the local defect configuration rapidly changes to a stable state, where the other type of carrier is captured and recombined through another defect level. This novel mechanism is applied to the recombination center Te(cd)(2+) in CdTe. We show that this two-level process can significantly increase the recombination rate (by three orders of magnitude) in agreement with experiments. We expect that this two-level recombination process can exist in a wide range of semiconductors, so its effect should be carefully examined in characterizing optoelectronic materials. PMID- 26880668 TI - Extended prediction rule to optimise early detection of heart failure in older persons with non-acute shortness of breath: a cross-sectional study. AB - OBJECTIVES: There is a need for a practical tool to aid general practitioners in early detection of heart failure in the elderly with shortness of breath. In this study, such a screening rule was developed based on an existing rule for detecting heart failure in older persons with a diagnosis of chronic obstructive pulmonary disease. The original rule included a history of ischaemic heart disease, body mass index, laterally displaced apex beat, heart rate, elevated N terminal pro B-type natriuretic peptide and an abnormal ECG. DESIGN: Cross sectional data were used to validate, update and extend the original prediction rule according to a standardised state-of-the-art stepwise approach. SETTING: Primary care with 30 participating general practices. PARTICIPANTS: Community dwelling people aged >= 65 years with shortness of breath on exertion. METHODS AND RESULTS: Validation of the existing screening rule in our population showed satisfying discrimination with a concordance statistic of 0.84 (range 0.80-0.85), but poor calibration. Performance measures were most improved by adding the predictors age >75 years, peripheral oedema and systolic murmur, resulting in a concordance statistic of 0.88 (range 0.85-0.90) and a net reclassification improvement of 31%. A risk score was computed, which showed high accuracy with a negative predictive value of 87% and a positive predictive value of 73%. Evaluating the improved rule in the derivation set and an independent set of patients with type 2 diabetes aged 60 years or older showed satisfying generalisability of the rule. CONCLUSIONS: Our rule resulted in excellent prediction of heart failure in the large domain of the elderly with shortness of breath, and would help general practitioners to select those needing echocardiography. TRIAL REGISTRATION NUMBER: NCT01202006. PMID- 26880669 TI - Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta analysis. AB - OBJECTIVE: To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). DESIGN: This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. OUTCOME MEASURES: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. RESULTS: 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. CONCLUSIONS: NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators. PMID- 26880670 TI - The China Patient-Centred Evaluative Assessment of Cardiac Events (China PEACE) Prospective Study of 3-Vessel Disease: rationale and design. AB - INTRODUCTION: Complex coronary artery disease (left main and three-vessel disease) carries high risks of adverse events and cost burden. However, in China, little is known about which patients are directed toward which treatment strategies and what outcomes are being achieved. METHODS AND ANALYSIS: Using the China PEACE (Patient-centered Evaluative Assessment of Cardiac Events) research network, this prospective study of three-Vessel Disease, the China PEACE-3VD study, has a plan to consecutively register over 4000 patients with a diagnosis of 3VD and/or left-main disease by elective coronary angiography at 24 large cardiovascular centres in China. We centrally conducted medical record abstraction and SYNTAX Score calculation for all registered patients. The sites invited patients to the prospective cohort, and conducted 1-year follow-up on major events, including cardiac events, symptoms, secondary prevention and quality of life. The estimated entire sample size of eligible patients of 4000 was determined based on both feasibility and consideration of adequate statistical precision for describing the treatment decisions, guidelines adherence and appropriateness of treatment for patients with complex coronary artery diseases. The study is designed to investigate patient, clinician and hospital factors associated with each treatment strategy (percutaneous coronary intervention, coronary artery bypass grafting or medical therapy) as well as appropriateness of treatment choice, current guideline compliance and patient reported outcomes for patients with complex coronary artery disease in large cardiovascular centres in China, as a foundation for enhanced knowledge in the field and to assist quality improvement initiatives. ETHICS AND DISSEMINATION: The study protocol was approved by the ethics committee at the China National Center for Cardiovascular Diseases. Findings will be shared with participating hospitals, policymakers and the academic community, to promote quality monitoring, quality improvement and the efficient allocation, and use of coronary revascularisation procedures in China. TRIAL REGISTRATION NUMBER: NCT01625312; Pre-results. PMID- 26880671 TI - SCALS: a fourth-generation study of assisted living technologies in their organisational, social, political and policy context. AB - INTRODUCTION: Research to date into assisted living technologies broadly consists of 3 generations: technical design, experimental trials and qualitative studies of the patient experience. We describe a fourth-generation paradigm: studies of assisted living technologies in their organisational, social, political and policy context. Fourth-generation studies are necessarily organic and emergent; they view technology as part of a dynamic, networked and potentially unstable system. They use co-design methods to generate and stabilise local solutions, taking account of context. METHODS AND ANALYSIS: SCALS (Studies in Co-creating Assisted Living Solutions) consists (currently) of 5 organisational case studies, each an English health or social care organisation striving to introduce technology-supported services to support independent living in people with health and/or social care needs. Treating these cases as complex systems, we seek to explore interdependencies, emergence and conflict. We employ a co-design approach informed by the principles of action research to help participating organisations establish, refine and evaluate their service. To that end, we are conducting in depth ethnographic studies of people's experience of assisted living technologies (micro level), embedded in evolving organisational case studies that use interviews, ethnography and document analysis (meso level), and exploring the wider national and international context for assisted living technologies and policy (macro level). Data will be analysed using a sociotechnical framework developed from structuration theory. ETHICS AND DISSEMINATION: Research ethics approval for the first 4 case studies has been granted. An important outcome will be lessons learned from individual co-design case studies. We will document the studies' credibility and rigour, and assess the transferability of findings to other settings while also recognising unique aspects of the contexts in which they were generated. Academic outputs will include a cross-case analysis and progress in theory and method of fourth-generation assisted living technology research. We will produce practical guidance for organisations, policymakers, designers and service users. PMID- 26880672 TI - HIV counselling and testing practices for children seen in an urban emergency department of a tertiary referral hospital in Dar es Salaam, Tanzania: a retrospective cross-sectional study. AB - OBJECTIVES: To describe the HIV counselling and testing practices for children presenting to an emergency department (ED) in a low-income country. SETTING: The ED of a large east African national referral hospital. PARTICIPANTS: This retrospective review of all paediatric (<18 years old) ED visits in 2012 enrolled patients who had an HIV test ordered and excluded those without testing. Files were available for 5540/5774 (96%) eligible patients and 1632 (30%) were tested for HIV, median age 1.3 years (IQR 9 months to 4 years), 58% <18 months old and 61% male. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was documentation of pretest and post-test counselling, or deferral of counselling, for children tested for HIV in the ED. Secondary measures included the overall rate of HIV testing, rate of counselling documented in the inpatient record when deferred in the ED, rate of counselling documented when testing was initiated by the inpatient service, rate of counselling documented by test result (positive vs negative) and the rate of referral to follow-up HIV care among patients testing positive. RESULTS: Of 418 patients tested in the ED, counselling, or deferral of counselling, was documented for 70 (17%). When deferred to the ward, subsequent counselling was documented for 15/42 (36%). Counselling was documented in 33% of patients testing positive versus 1.1% patients testing negative (OR 43 (95% CI 23 to 83). Of 199 patients who tested positive and survived to hospital discharge, 76 (38%) were referred for follow-up at the HIV clinic on discharge. CONCLUSIONS: Physicians documented the provision, or deferral, of counselling for <20% of children tested for HIV in the ED. Counselling was much more likely to be documented when the test result was positive. Less than 40% of those testing positive were referred for follow-up care. PMID- 26880674 TI - On "Implementing the Use of Chemical-Free Products in a Perinatal Unit". PMID- 26880675 TI - Potentially harmful secondary metabolites produced by indoor Chaetomium species on artificially and naturally contaminated building materials. AB - The presence of the fungal genus Chaetomium and its secondary metabolites in indoor environments is suspected to have a negative impact on human health and well-being. About 200 metabolites have been currently described from Chaetomium spp., but only the bioactive compound group, chaetoglobosins, have been screened for and thus detected in buildings. In this study, we used a liquid chromatography high-resolution mass spectrometry approach to screen both artificially and naturally infected building materials for all the Chaetomium metabolites described in the literature. Pure agar cultures were also investigated to establish differences between metabolite production in vitro and on building materials as well as in comparison with non-indoor reference strains. On building materials, six different chaetoglobosins were detected in total concentrations of up to 950 mg/m2 from Chaetomium globosum along with three different chaetoviridins/chaetomugilins in concentrations up to 200 mg/m2 . Indoor Chaetomium spp. preferred wood-based materials over gypsum, both in terms of growth rate and metabolite production. Cochliodones were detected for the first time on all building materials infected by both C. globosum and Chaetomium elatum and are thus candidates as Chaetomium biomarkers. No sterigmatocystin was produced by Chaetomium spp. from indoor environment. PMID- 26880673 TI - Copying hierarchical leaders' voices? Acoustic plasticity in female Japanese macaques. AB - It has been historically claimed that call production in nonhuman primates has been shaped by genetic factors, although, recently socially-guided plasticity and cortical control during vocal exchanges have been observed. In humans, context dependent vocal convergence with relatives, friends or leaders' voices can be found. Comparative studies with monkeys and apes presenting tolerant social organizations have demonstrated that affiliative bonding is the determining factor of convergence. We tested whether vocal copying could also exist in a primate species with a despotic social organization. We compared the degree of inter-individual similarity of contact calls in two groups of Japanese macaques as a function of age, dominance rank, maternal kin and affiliative bonds. We found a positive relationship between dyadic acoustic similarity and female rank differences. Since most call exchanges were initiated by dominant females and since this species is known for the ability of responders to acoustically match initiators' calls, we conclude that high social status may motivate vocal convergence in this despotic society. Accordingly, intra-individual comparisons showed that isolated calls were more stereotyped than exchanged calls, and that dominants had more stereotyped voices than subordinates. This opens new lines of research with regard to social motivation guiding acoustic plasticity in primates. PMID- 26880676 TI - OUTCOMES AND PROGNOSTIC FACTORS ASSOCIATED WITH CANINE SINONASAL TUMORS TREATED WITH CURATIVE INTENT CONE-BASED STEREOTACTIC RADIOSURGERY (1999-2013). AB - Stereotactic radiosurgery (SRS) is a relatively new therapeutic option in veterinary oncology. The role of this modality has not been extensively evaluated for the use in canine nasal tumors. The objective of this retrospective, observational study was to describe the clinical outcome and prognostic factors associated with survival times in a sample of canine patients treated with SRS for sinonasal tumors. Fifty-seven dogs with sinonasal tumors met inclusion criteria. Histologic diagnoses included sarcoma (SA) (n = 9), carcinoma (CA) (n = 40), osteosarcoma (OSA) (n = 7), and round cell (n = 1). Four of 57 cases were treated twice with SRS. For these, the median and mean doses delivered were 30Gy and 33Gy, respectively (range 18.75Gy-56Gy). Late effects occurred in 23 cases and ranged from grades I-III. The median overall survival time was 8.5 months. The median overall survival times in dogs with tumor type of CA, SA, and OSA were 10.4, 10.7, and 3.1 months, respectively. Dogs with the tumor type of OSA had shorter overall survival time than that in dogs with tumor type of CA and SA. Findings from this retrospective study indicated that SRS may be beneficial for canine patients with sinonasal tumors, however a controlled clinical trial would be needed to confirm this. Prospective studies are also needed to better define the role of SRS as palliative or curative, and to further investigate the risk of clinically significant toxicity. PMID- 26880677 TI - Environmental variation alters the fitness effects of rifampicin resistance mutations in Pseudomonas aeruginosa. AB - The fitness effects of antibiotic resistance mutations in antibiotic-free conditions play a key role in determining the long-term maintenance of resistance. Although resistance is usually associated with a cost, the impact of environmental variation on the cost of resistance is poorly understood. Here, we test the impact of heterogeneity in temperature and resource availability on the fitness effects of antibiotic resistance using strains of the pathogenic bacterium Pseudomonas aeruginosa carrying clinically important rifampicin resistance mutations. Although the rank order of fitness was generally maintained across environments, fitness effects relative to the wild type differed significantly. Changes in temperature had a profound impact on the fitness effects of resistance, whereas changes in carbon substrate had only a weak impact. This suggests that environmental heterogeneity may influence whether the costs of resistance are likely to be ameliorated by second-site compensatory mutations or by reversion to wild-type rpoB. Our results highlight the need to consider environmental heterogeneity and genotype-by-environment interactions for fitness in models of resistance evolution. PMID- 26880678 TI - Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor-Binding Protein 3 in Relation to the Risk of Type 2 Diabetes Mellitus: Results From the EPIC-Potsdam Study. AB - Higher levels of insulin-like growth factor-binding protein 3 (IGFBP-3) might raise the risk of type 2 diabetes mellitus (T2DM) via binding of insulin-like growth factor 1 (IGF-1), an insulin-like hormone that is involved in glucose homeostasis. We investigated serum concentrations of IGF-1 and IGFBP-3 and their molar ratio in relation to T2DM incidence in a nested case-cohort study within the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. We included a randomly selected subcohort of persons without T2DM at the time of blood sampling (n = 2,269) and 776 individuals with incident T2DM identified between 1994 and 2005. For the highest quartile versus lowest, the multivariable adjusted hazard rate ratios were 0.91 (95% confidence interval (CI): 0.68, 1.23; P for trend = 0.31) for IGF-1, 1.33 (95% CI: 1.00, 1.76; P for trend = 0.04) for IGFBP-3, and 0.77 (95% CI: 0.57, 1.03; P for trend = 0.03) for IGF-1:IGFBP-3 ratio. IGFBP-3 level remained positively associated with T2DM incidence-and the ratio of IGF-1 to IGFBP-3 was inversely related with T2DM incidence--in models that included adjustment for IGF-1 concentrations (P for trend < 0.05). Therefore, our findings do not confirm an association between total IGF-1 concentrations and risk of T2DM in the general study population, although higher IGFBP-3 levels might raise T2DM risk independent of IGF-1 levels. PMID- 26880679 TI - A randomized controlled trial of the effect of a photographic display with and without music on pre-operative anxiety. AB - AIMS: To determine the effectiveness of photographic display at reducing pre operative anxiety in an ear, nose and throat surgery unit; alone and in combination with music. BACKGROUND: The waiting time prior to the surgery is often unpleasant and a time of anxiety for patients. Anxiety can affect physical recovery and psychological well-being; lengthening convalescence and hospital stay after the surgery. Improving pre-operative anxiety is a challenge with potential impacts on improving patients' satisfaction and well-being and decreasing the cost of care. DESIGN: A clinical trial was conducted with two intervention groups and one control group. METHODS: The sample consisted of 180 subjects from the otolaryngology major ambulatory surgery unit in a tertiary hospital in the province of Granada, with 60 subjects per group. The outcome variables measured were state anxiety, heart and respiratory rate and blood pressure. The data were collected from May-December 2013. RESULTS: After the intervention, in the comparison between control group and photographic display group, all variables had lower means in the intervention group, although a significant P value was only obtained for respiratory rate using one-way anova test. When comparing control group and photographic display combined with music group, using one-way anova test, all mean values were lower in the intervention group and a significant P value were observed for all variables except diastolic blood pressure. CONCLUSION: Photographic display in combination with music is more effective at reducing pre-operative anxiety than the standard intervention and photographic display alone. PMID- 26880681 TI - Controllable Synthesis of Mesoporous Iron Oxide Nanoparticle Assemblies for Chemoselective Catalytic Reduction of Nitroarenes. AB - Iron(III) oxide is a low-cost material with applications ranging from electronics to magnetism, and catalysis. Recent efforts have targeted new nanostructured forms of Fe2O3 with high surface area-to-volume ratio and large pore volume. Herein, the synthesis of 3D mesoporous networks consisting of 4-5 nm gamma-Fe2O3 nanoparticles by a polymer-assisted aggregating self-assembly method is reported. Iron oxide assemblies obtained from the hybrid networks after heat treatment have an open-pore structure with high surface area (up to 167 m(2)g(-1)) and uniform pores (ca. 6.3 nm). The constituent iron oxide nanocrystals can undergo controllable phase transition from gamma-Fe2O3 to alpha-Fe2O3 and to Fe3O4 under different annealing conditions while maintaining the 3D structure and open porosity. These new ensemble structures exhibit high catalytic activity and stability for the selective reduction of aryl and alkyl nitro compounds to the corresponding aryl amines and oximes, even in large-scale synthesis. PMID- 26880680 TI - Association between adiposity and cognitive function in young men: Hormonal mechanisms. AB - OBJECTIVE: To determine the association between adiposity, hormones, and cognition in young men with abdominal obesity. METHODS: In this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2) ; age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined. RESULTS: Total fat percentage was negatively associated with visuospatial skills (P = 0.002) and visual memory (P = 0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P = 0.05 and trend, P = 0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P = 0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P = 0.015 and trend, P = 0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P = 0.05) and showed a trend for verbal learning and memory (P = 0.09). CONCLUSIONS: Adiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels. PMID- 26880682 TI - Differential gene expression patterns during embryonic development of sea urchin exposed to triclosan. AB - Triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a broad-spectrum antibacterial agent used in common industrial, personal care and household products which are eventually rinsed down the drain and discharged with wastewater effluent. It is therefore commonly found in the aquatic environment, leading to the continual exposure of aquatic organisms to TCS and the accumulation of the antimicrobial and its harmful degradation products in their bodies. Toxic effects of TCS on reproductive and developmental progression of some aquatic organisms have been suggested but the underlying molecular mechanisms have not been defined. We investigated the expression patterns of genes involved in the early development of TCS-treated sea urchin Strongylocentrotus nudus using cDNA microarrays. We observed that the predominant consequence of TCS treatment in this model system was the widespread repression of TCS-modulated genes. In particular, empty spiracles homeobox 1 (EMX-1), bone morphogenic protein, and chromosomal binding protein genes showed a significant decrease in expression in response to TCS. These results suggest that TCS can induce abnormal development of sea urchin embryos through the concomitant suppression of a number of genes that are necessary for embryonic differentiation in the blastula stage. Our data provide new insight into the crucial role of genes associated with embryonic development in response to TCS. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 426-433, 2017. PMID- 26880683 TI - Role of palliative radiotherapy in the management of mural cardiac metastases: who, when and how to treat? A case series of 10 patients. AB - Cardiac metastases (CM), although a rare manifestation of metastatic cancer, are increasing in incidence with the improved prognosis and increased longevity of many patients with cancer. This condition may be life-threatening, especially for bulky rapidly growing tumors. Such cancer presentations may be amenable to palliative radiotherapy to improve symptoms and to prevent further cardiac function decline. Here, we report on our experience with 10 patients with mural CM who received radiotherapy (RT) to the heart with palliative intent. The radiation treatment was given in different clinical situations using different dose and fractionation, and with a variety of outcomes. Palliative RT was a reasonably effective treatment, leading to good radiographic response in five patients who were evaluable for radiologic response. The mean duration of response in responding patients was 6.3 months (range: 3-11 months). This report describing clinical dilemmas around CM radiation therapy summarizes the previous experiences with radiation in treatment of CM and may assist in the considerations of palliative treatment for these patients. PMID- 26880685 TI - Superspreading on Immersed Gel Surfaces for the Confined Synthesis of Thin Polymer Films. AB - Liquid spreading is of significant interest in science and technology. Although surface topography engineering and liquid surface-tension regulating can facilitate spreading, the spreading layers in these strategies are inevitably inhomogeneous or contaminated with surfactants. Herein, we show a general strategy to realize the superspreading of liquids on mutually soluble gel surfaces. The cooperation of the hydraulic pressure under liquid phase and liquid like property of gel surfaces can dramatically eliminate the local pinning effect and enhance the advancement of three-phase contact line, thus forming stable and homogeneous superspreading liquid layers. Such liquid layers can be converted into various functional thin polymer films with controlled thicknesses (nm- to um scale) through one-step polymerization of the reactants. Our strategy offers opportunities for large-scale synthesis of versatile functional thin films for various applications. PMID- 26880684 TI - Midlife work ability and mobility limitation in old age among non-disability and disability retirees--a prospective study. AB - BACKGROUND: Little is known about the wellbeing and mobility limitation of older disability retirees. Personal and environmental factors, such as time spent in working life, may either exacerbate or mitigate the onset of mobility limitation in general population. We aimed to study perceived midlife work ability as a determinant of self-reported mobility limitation in old age among municipal employees who transitioned into non-disability and disability retirement. METHODS: 4329 participants of the Finnish Longitudinal Study of Municipal Employees (FLAME) had retired during January 1985 and July 2000. They had data on retirement, perceived work ability in 1985, and self-reported mobility limitation (non-disability retirement n = 2870, men 39%; and diagnose-specific disability retirement n = 1459, men 48%). Self-reported mobility was measured in 1985, 1992, 1997 and 2009. The latest score available was used to assess the number of mobility limitation. Work ability was measured by asking the respondents to evaluate their current work ability against their lifetime best in 1985. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for work ability predicting mobility limitation in non-disability and diagnose-specific disability retirement groups were calculated using Poisson regression models. RESULTS: The prevalence of mobility limitation for those who transitioned into non-disability retirement (Incidence Rate, IR = 0.45, 95% CI = 0.44-0.46) was lower compared to those who retired due to disability (IR = 0.65, CI = 0.63-0.66). A one-point increase in the work ability score decreased the risk for having one more mobility limitation among non-disability and all diagnose-specific retirement groups (musculoskeletal disease, cardiovascular disease, mental disorder, and other diseases). CONCLUSIONS: Better midlife work ability may protect from old age mobility limitation among those who retire due to non-disability and disability. Promoting work ability in midlife may lead to more independent, active aging, regardless of type of retirement. PMID- 26880686 TI - Cobalt Sulfide/Graphene Composite Hydrogel as Electrode for High-Performance Pseudocapacitors. AB - Graphene and its composite hydrogels with interconnected three-dimensional (3D) structure have raised continuous attention in energy storage. Herein, we describe a simple hydrothermal strategy to synthesize 3D CoS/graphene composite hydrogel (CGH), which contains the reduction of GO sheets and anchoring of CoS nanoparticles on graphene sheets. The formed special 3D structure endows this composite with high electrochemical performance. Remarkably, the obtained 3D CGH exhibits high specific capacitance (C(s)) of 564 F g(-1) at a current density of 1 A g(-1) (about 1.3 times higher than pure CoS), superior rate capability and high stability. It is worth mentioning that this methodology is readily adaptable to decorating CoS nanoparticles onto graphene sheets and may be extended to the preparation of other pseudocapacitive materials based on graphene hydrogels for electrochemical applications. PMID- 26880687 TI - Watch your step! A frustrated total internal reflection approach to forensic footwear imaging. AB - Forensic image retrieval and processing are vital tools in the fight against crime e.g. during fingerprint capture. However, despite recent advances in machine vision technology and image processing techniques (and contrary to the claims of popular fiction) forensic image retrieval is still widely being performed using outdated practices involving inkpads and paper. Ongoing changes in government policy, increasing crime rates and the reduction of forensic service budgets increasingly require that evidence be gathered and processed more rapidly and efficiently. A consequence of this is that new, low-cost imaging technologies are required to simultaneously increase the quality and throughput of the processing of evidence. This is particularly true in the burgeoning field of forensic footwear analysis, where images of shoe prints are being used to link individuals to crime scenes. Here we describe one such approach based upon frustrated total internal reflection imaging that can be used to acquire images of regions where shoes contact rigid surfaces. PMID- 26880688 TI - Plasma concentration of high-mobility group box 1 (HMGB1) after 100 drop to vertical jumps and after a 1200-km bicycle race. AB - High-mobility group box 1 (HMGB1) has recently been reported to be involved in proinflammation and tissue repair. Therefore, we hypothesized that HMGB1 is released into the bloodstream after eccentric exercises or prolonged endurance activities. Blood samples from 11 participants that performed 100 drop to vertical jumps (DVJ) and from 10 participants that took part in the 1200-km 'Paris-Brest-Paris' bicycle race (PBP) were tested for HMGB1 and creatine kinase (CK) levels. CK increased after both DVJ (pre: 150.6 +/- 81.5 U/L; post: 188.8 +/ 95.5 U/L 8 h: 790.5 +/- 346.4 U/L) and PBP (pre: 81.3 +/- 36.4 U/L; post: 725.2 +/- 229.5 U/L; 12 h: 535.8 +/- 188.6 U/L), indicating membrane damage. However, HMGB1 plasma levels remained below the detection limit (78 pg/mL) of the applied enzyme-linked immunosorbent assay kit for all blood samples analysed. That is, neither high intensity eccentric exercises (DVJ) nor prolonged endurance events (PBP) seemed to affect HMGB1 levels in blood at selected time points. PMID- 26880690 TI - Does the morphology of the ear of the Chinese bamboo rat (Rhizomys sinensis) show "Subterranean" characteristics? AB - In spite of the growing interest in rodents with subterranean activity in general and the spalacids (Spalacidae) in particular, little is known about the biology of most members of this clade, such as the Chinese bamboo rat (Rhizomys sinensis). Here, we analyzed the ear morphology of R. sinensis with respect to hearing specialization for subterranean or aboveground modes of communication. It is well-known that ecology and style of life of a particular species can be reflected in morphology of its ear, its hearing and vocalization, so we expect that such information could provide us insight into its style of life and its sensory environment. The ratio between the eardrum and stapedial footplate areas, which influences the efficiency of middle ear sound transmission, suggests low hearing sensitivity, as is typical for subterranean species. The cochlea had 3.25 coils and resembled species with good low frequency hearing typical for subterranean mammals. The length of the basilar membrane was 18.9 +/- 0.8 mm and its width slowly increased towards the cochlear apex from 60 to 85 MUm. The mean density of outer hair cells was 344 +/- 22 and of inner hair cells 114 +/- 7.3 per 1 mm length of the organ of Corti, and increased apically. These values (except for relatively low hair cell density) usually characterize ears specialized for low frequency hearing. There was no evidence for an acoustic fovea. Apart of low hair cell density which is common in aboveground animals, this species has also relatively large auricles, suggesting the importance of sound localization during surface activity. The ear of the Chinese bamboo rat thus contains features typical for both aboveground and subterranean mammals and suggests that this spalacid has fossorial habits combined with regular aboveground activity. PMID- 26880691 TI - Transgenerational transmission of systemic mast cell activation disease-genetic and epigenetic features. AB - Systemic mast cell activation disease (MCAD) comprises disorders characterized by an enhanced release of mast cell mediators accompanied by a varying accumulation of dysfunctional mast cells. Within the last years, evidence has been presented that MCAD is a multifactorial polygenic determined disease with the KIT(D816V) mutation and its induced functional consequences considered as special case. The respective genes encode proteins for various signaling pathways, epigenetic regulators, the RNA splicing machinery, and transcription factors. Transgenerational transmission of MCAD appears to be quite common. The basics of the molecular mechanisms underlying predisposition of the disease, that is, somatic and germline mutations and the contribution of epigenetic processes have become identifiable. The aim of the present review is to present and discuss available genetic, epigenetic and epidemiological findings, and to present a model of MCAD pathogenesis. PMID- 26880689 TI - Dynamic functional network connectivity reveals unique and overlapping profiles of insula subdivisions. AB - The human insular cortex consists of functionally diverse subdivisions that engage during tasks ranging from interoception to cognitive control. The multiplicity of functions subserved by insular subdivisions calls for a nuanced investigation of their functional connectivity profiles. Four insula subdivisions (dorsal anterior, dAI; ventral, VI; posterior, PI; middle, MI) derived using a data-driven approach were subjected to static- and dynamic functional network connectivity (s-FNC and d-FNC) analyses. Static-FNC analyses replicated previous work demonstrating a cognition-emotion-interoception division of the insula, where the dAI is functionally connected to frontal areas, the VI to limbic areas, and the PI and MI to sensorimotor areas. Dynamic-FNC analyses consisted of k means clustering of sliding windows to identify variable insula connectivity states. The d-FNC analysis revealed that the most frequently occurring dynamic state mirrored the cognition-emotion-interoception division observed from the s FNC analysis, with less frequently occurring states showing overlapping and unique subdivision connectivity profiles. In two of the states, all subdivisions exhibited largely overlapping profiles, consisting of subcortical, sensory, motor, and frontal connections. Two other states showed the dAI exhibited a unique connectivity profile compared with other insula subdivisions. Additionally, the dAI exhibited the most variable functional connections across the s-FNC and d-FNC analyses, and was the only subdivision to exhibit dynamic functional connections with regions of the default mode network. These results highlight how a d-FNC approach can capture functional dynamics masked by s-FNC approaches, and reveal dynamic functional connections enabling the functional flexibility of the insula across time. Hum Brain Mapp 37:1770-1787, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26880692 TI - Expanding the Scope of ENCODE. AB - The National Human Genome Research Institute has earmarked up to $38 million in grant funding for five new initiatives aimed at expanding ENCODE, its database of functional elements in human and mouse genomes. For the first time, grantees will focus on diseased tissue samples in an effort to understand how these functional elements influence the development of cancer and other diseases. PMID- 26880693 TI - Obesity and emotional well-being in adolescents: Roles of body dissatisfaction, loss of control eating, and self-rated health. AB - OBJECTIVE: Weak or inconsistent association between obesity and impairment in emotional well-being in population-based samples has led to efforts to identify mediating variables. This study examined the relative importance of body dissatisfaction (BD), loss of control (LOC) eating, and self-rated health (SRH) in mediating the association between obesity and impairment in emotional well being in a school-based sample of adolescents (boys, n = 437; girls, n = 950). METHODS: Moderated mediation analysis was employed to assess the relative importance of the putative mediating variables and moderation of mediation effects by sex following the methods suggested by Hayes and coworkers. RESULTS: BD and SRH, but not LOC eating, were found to mediate the association between obesity and impairment in emotional well-being. Stronger mediation effects were observed for BD than for SRH. None of these results was moderated by sex. CONCLUSIONS: The findings suggest that it may be important to target BD in obesity prevention and treatment programs in order to reduce the adverse impact of excess body weight on young people's emotional well-being. PMID- 26880694 TI - A randomised, controlled trial of the effects of a mobile telehealth intervention on clinical and patient-reported outcomes in people with poorly controlled diabetes. AB - Objective The objective of this research is to determine the effects of mobile telehealth (MTH) on glycosylated haemoglobin (HbA1c) and other clinical and patient-reported outcomes in insulin-requiring people with diabetes. Methods A nine-month randomised, controlled trial compared standard care to standard care supplemented with MTH (self-monitoring, mobile-phone data transmissions, graphical and nurse-initiated feedback, and educational calls). Clinical (HbA1c, blood pressure, daily insulin dose, diabetes outpatient appointments (DOAs)) and questionnaire data (health-related quality of life, depression, anxiety) were collected. Mean group changes over time were compared using hierarchical linear models and Mann-Whitney tests. Results Eighty-one participants with a baseline HbA1c of 8.98% +/- 1.82 were randomised to the intervention ( n = 45) and standard care ( n = 36). The Group by Time effect revealed MTH did not significantly influence HbA1c ( p = 0.228), but p values were borderline significant for blood pressure ( p = 0.054) and mental-health related quality of life ( p = 0.057). Examination of effect sizes and 95% confidence intervals for mean group differences at nine months supported the existence of a protective effect of MTH on mental health-related quality of life as well as depression. None of the other measured outcomes were found to be affected by the MTH intervention. Conclusions Findings from this study must be interpreted with caution given the small sample size, but they do not support the widespread adoption of MTH to achieve clinically significant changes in HbA1c. MTH may, however, have positive effects on blood pressure and protective effects on some aspects of mental health. PMID- 26880695 TI - Do weight management interventions delivered by online social networks effectively improve body weight, body composition, and chronic disease risk factors? A systematic review. AB - Introduction Currently, no systematic review/meta-analysis has examined studies that used online social networks (OSN) as a primary intervention platform. Therefore, the purpose of this review was to evaluate the effectiveness of weight management interventions delivered through OSN. Methods PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched (January 1990-November 2015) for studies with data on the effect of OSNs on weight loss. Only primary source articles that utilized OSN as the main platform for delivery of weight management/healthy lifestyle interventions, were published in English language peer-reviewed journals, and reported outcome data on weight were eligible for inclusion in this systematic review. Five articles were included in this review. Results One hundred percent of the studies ( n = 5) reported a reduction in baseline weight. Three of the five studies (60%) reported significant decreases in body weight when OSN was paired with health educator support. Only one study reported a clinical significant weight loss of >=5%. Conclusion Using OSN for weight management is in its early stages of development and, while these few studies show promise, more research is needed to acquire information about optimizing these interventions to increase their efficacy. PMID- 26880696 TI - Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Europium(III) DO3A as a Bimodal Imaging Probe. AB - A new prototype consisting of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles decorated with europium(III) ions encapsulated in a DO3A organic scaffold was designed as a platform for further development of bimodal contrast agents for MRI and optical imaging. The USPIO nanoparticles act as negative MRI contrast agents, whereas the europium(III) ion is a luminophore that is suitable for use in optical imaging detection. The functionalized USPIO nanoparticles were characterized by TEM, DLS, XRD, FTIR, and TXRF analysis, and a full investigation of the relaxometric and optical properties was conducted. The typical luminescence emission of europium(III) was observed and the main red emission wavelength was found at 614 nm. The relaxometric study of these ultrasmall nanoparticles showed r2 values of 114.8 mM(-1) Fes(-1) at 60 MHz, which is nearly double the r2 relaxivity of Sinerem((r)). PMID- 26880697 TI - Immunotherapy for Gastric Cancer: A Focus on Immune Checkpoints. AB - Gastric cancer (GC) is a major world-wide health problem. It is the third leading cause of death from cancer. The treatment of advanced GC by chemotherapy has limited efficacy. The addition of some targeted therapies like trastuzumab and ramucirumab have added a modest benefit, but only in human epidermal growth factor receptor 2 (ERBB2 or HER2)-positive patients and in the second-line setting, respectively. The development of new and effective therapeutic strategies must consider the genetic complexity and heterogeneity of GC; prognostic and predictive biomarkers should be identified for clinical implementation. Immune deregulation has been associated with some GC subtypes, especially those that are associated with virus infection and those with a high mutational rate. Different mechanisms to prevent immunologic escape have been characterized during the last years; in particular the PD-1/PD-L1 inhibitors pembrolizumab, avelumab, durvalumab and atezolizumab have shown early sign of efficacy. Therefore, immunotherapeutic strategies may provide new opportunities for GC patients. This review will discuss (1) the main characteristics of GC treatment, (2) the immune response in GC, and (3) the current status of immune related strategies in clinical development in GC patients, focusing on immune checkpoints therapies. PMID- 26880698 TI - Effects of lipopolysaccharide, multiwalled carbon nantoubes, and the combination on lung alveolar epithelial cells. AB - Multiwalled carbon nanotubes (MWCNT) have been shown to induce lung fibrosis in animal models, however the underlying molecular factors/mechanisms are still unclear. In this study, we investigated the effects of lipopolysaccharide (LPS), MWCNT, and the combination of LPS and MWCNT on the expression of matrix metalloproteinase-9 and metalloproteinase-12 (MMP-9, MMP-12), collagen 3A1 (Col3A1), and transforming growth factor beta (TGFbeta) in alveolar epithelial A549 cells. MMPs are proteinases that degrade extracellular matrix and play a role in lung fibrosis. A549 cells were exposed to LPS (1 ng/mL), MWCNT (20 MUg/mL), and the combination and analyzed for paracellular permeability, TGFbeta, Col3A1, MMP-9, MMP-12, NF-kappaB activation, and cell migration by real-time PCR and immunofluorescence. LPS, the combination of LPS and MWCNT, and MWCNT only at the highest tested dose induced blue dextran extravasation. LPS and MWCNT increased the expression of TGFbeta and its downstream target gene Col3A, and MMP 9 and MMP-12 mRNA. MWCNT potently induced cell migration toward wound healing, whereas LPS slightly induced cell migration. Both, LPS and MWCNT, induced NF kappaB nuclear translocation. Our results indicate that MWCNT activated alveolar epithelial cells to promote fibrogenesis, and that LPS differentially primes molecular factors involved in lung remodeling. These findings suggest a role of alveolar epithelial cells in fibrogenesis and also may aid in the design and development of tests for screening of fibrogenic agents. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 445-455, 2017. PMID- 26880700 TI - A jumping shape memory alloy under heat. AB - Shape memory alloys are typical temperature-sensitive metallic functional materials due to superelasticity and shape recovery characteristics. The conventional shape memory effect involves the formation and deformation of thermally induced martensite and its reverse transformation. The shape recovery process usually takes place over a temperature range, showing relatively low temperature-sensitivity. Here we report novel Cu-Al-Fe-Mn shape memory alloys. Their stress-strain and shape recovery behaviors are clearly different from the conventional shape memory alloys. In this study, although the Cu-12.2Al-4.3Fe 6.6Mn and Cu-12.9Al-3.8Fe-5.6Mn alloys possess predominantly L2(1) parent before deformation, the 2H martensite stress-induced from L2(1) parent could be retained after unloading. Furthermore, their shape recovery response is extremely temperature-sensitive, in which a giant residual strain of about 9% recovers instantly and completely during heating. At the same time, the phenomenon of the jumping of the sample occurs. It is originated from the instantaneous completion of the reverse transformation of the stabilized 2H martensite. This novel Cu-Al Fe-Mn shape memory alloys have great potentials as new temperature-sensitive functional materials. PMID- 26880699 TI - A novel approach to predict cetuximab-induced hypersensitivity reaction: detection of drug-specific IgE on basophils. AB - Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab-specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab-induced HR. Twelve head and neck cancer patients were enrolled in this single-institution study: four with a history of cetuximab-induced HR and eight with no such history. Cetuximab-specific and galactose-alpha-1,3-galactose (alpha-gal) specific IgEs in serum were measured in vitro using an enzyme-linked immunosorbent assay (ELISA). IgE-cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcepsilonRI. The positive predictive value associated with the presence of cetuximab- or alpha-gal specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P < 0.05). However, this was not the case in patients who did not develop HR. In conclusion, our results strongly imply that the IgE-cetuximab interaction on basophils may be key to developing improved methods for predicting severe cetuximab-induced HR. PMID- 26880701 TI - Genetic analysis of arsenic accumulation in maize using QTL mapping. AB - Arsenic (As) is a toxic heavy metal that can accumulate in crops and poses a threat to human health. The genetic mechanism of As accumulation is unclear. Herein, we used quantitative trait locus (QTL) mapping to unravel the genetic basis of As accumulation in a maize recombinant inbred line population derived from the Chinese crossbred variety Yuyu22. The kernels had the lowest As content among the different maize tissues, followed by the axes, stems, bracts and leaves. Fourteen QTLs were identified at each location. Some of these QTLs were identified in different environments and were also detected by joint analysis. Compared with the B73 RefGen v2 reference genome, the distributions and effects of some QTLs were closely linked to those of QTLs detected in a previous study; the QTLs were likely in strong linkage disequilibrium. Our findings could be used to help maintain maize production to satisfy the demand for edible corn and to decrease the As content in As-contaminated soil through the selection and breeding of As pollution-safe cultivars. PMID- 26880703 TI - Healthcare leadership and the ethics of managing expectations of caregivers and patients. AB - Healthcare providers and patients are often disappointed by the level of care public hospitals can deliver. The remedy is to lower expectations. Providers should be brought to see their obligations as only to give the best care resources allow. The public should be clearly told what care hospitals can and cannot provide and involved in decision-making. Healthcare leaders can play innovative roles in both these remedies. PMID- 26880702 TI - Degradation of Akt using protein-catalyzed capture agents. AB - Abnormal signaling of the protein kinase Akt has been shown to contribute to human diseases such as diabetes and cancer, but Akt has proven to be a challenging target for drugging. Using iterative in situ click chemistry, we recently developed multiple protein-catalyzed capture (PCC) agents that allosterically modulate Akt enzymatic activity in a protein-based assay. Here, we utilize similar PCCs to exploit endogenous protein degradation pathways. We use the modularity of the anti-Akt PCCs to prepare proteolysis targeting chimeric molecules that are shown to promote the rapid degradation of Akt in live cancer cells. These novel proteolysis targeting chimeric molecules demonstrate that the epitope targeting selectivity of PCCs can be coupled with non-traditional drugging moieties to inhibit challenging targets. PMID- 26880704 TI - Health sector changes must reach further. AB - Change management is relevant for healthcare leaders at all levels. This article offers a literature review and pulls from the author's own experience to emphasize the importance of transformative, sustainable change. Leaders are reminded that change comes from within, draws from all levels of the organization, and must be pervasive throughout a project. PMID- 26880705 TI - Gamma scintigraphy and biodistribution of (99m)Tc-cefotaxime sodium in preclinical models of bacterial infection and sterile inflammation. AB - (99m)Tc-cefotaxime sodium ((99m)Tc-CEF) was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose, and reducing agent type. Labeling studies were performed by changing the selected parameters one by one, and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Simple method for radiolabeling of CEF with (99m)Tc has been developed and standardized. Labeling efficiency of (99m)Tc-CEF was assessed by both radio thin-layer chromatography and radio high-performance liquid chromatography and found higher than 90%. The labeled compound was found to be stable in saline and human serum up to 24 h. Two different freeze dry kits were developed and evaluated. Based on the data obtained from this study, both products were stable for 6 months with high labeling efficiency. The prepared cold kit was found sterile and pyrogen free. The bacterial infection and sterile inflammation imaging capacity of (99m)Tc-CEF was evaluated. Based on the in vivo studies, (99m)Tc-CEF has higher uptake in infected and inflamed thigh muscle than healthy thigh muscle. PMID- 26880706 TI - Rotary orbital suspension culture of embryonic stem cell-derived neural stem/progenitor cells: impact of hydrodynamic culture on aggregate yield, morphology and cell phenotype. AB - Embryonic stem (ES)-derived neural stem/progenitor cells (ES-NSPCs) constitute a promising cell source for application in cell therapies for the treatment of central nervous system disorders. In this study, a rotary orbital hydrodynamic culture system was applied to single-cell suspensions of ES-NSPCs, to obtain homogeneously-sized ES-NSPC cellular aggregates (neurospheres). Hydrodynamic culture allowed the formation of ES-NSPC neurospheres with a narrower size distribution than statically cultured neurospheres, increasing orbital speeds leading to smaller-sized neurospheres and higher neurosphere yield. Neurospheres formed under hydrodynamic conditions (72 h at 55 rpm) showed higher cell compaction and comparable percentages of viable, dead, apoptotic and proliferative cells. Further characterization of cellular aggregates provided new insights into the effect of hydrodynamic shear on ES-NSPC behaviour. Rotary neurospheres exhibited reduced protein levels of N-cadherin and beta-catenin, and higher deposition of laminin (without impacting fibronectin deposition), matrix metalloproteinase-2 (MMP-2) activity and percentage of neuronal cells. In line with the increased MMP-2 activity levels found, hydrodynamically-cultured neurospheres showed higher outward migration on laminin. Moreover, when cultured in a 3D fibrin hydrogel, rotary neurospheres generated an increased percentage of neuronal cells. In conclusion, the application of a constant orbital speed to single-cell suspensions of ES-NSPCs, besides allowing the formation of homogeneously-sized neurospheres, promoted ES-NSPC differentiation and outward migration, possibly by influencing the expression of cell-cell adhesion molecules and the secretion of proteases/extracellular matrix proteins. These findings are important when establishing the culture conditions needed to obtain uniformly sized ES-NSPC aggregates, either for use in regenerative therapies or in in vitro platforms for biomaterial development or pharmacological screening. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26880707 TI - Advance care planning in an acute care world. PMID- 26880709 TI - Association between Helicobacter pylori infection and insulin resistance: a meta analysis. PMID- 26880710 TI - Thorax at 70. PMID- 26880708 TI - Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients. AB - Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P < 0.001). In patients who received second-line crizotinib therapy, the median PFS was 9.9 months (95% CI: 6.4-13.4 months). The difference between first-line and second line crizotinib treatment was not statistically significant (adjusted hazard ratio for progression, 0.56; 95% CI: 0.29-1.11; P = 0.092). Thus, there was a significant PFS benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. PMID- 26880712 TI - Reversible Morphological Evolution of Responsive Giant Vesicles to Nanospheres by the Self-Assembly of Crystalline-b-Coil Polyphosphazene Block Copolymers. AB - The preparation of long-term-stable giant unilamellar vesicles (GUVs, diameter >= 1000 nm) and large vesicles (diameter >= 500 nm) by self-assembly in THF of the crystalline-b-coil polyphosphazene block copolymers [N=P(OCH2CF3)2 ]n-b [N=PMePh]m (4 a: n=30, m=20; 4 b: n=90, m=20; 4 c: n=200, m=85), which combine crystalline [N=P(OCH2CF3)2] and amorphous [N=PMePh] blocks, both of which are flexible, is reported. SEM, TEM, and wide-angle X-ray scattering experiments demonstrated that the stability of these GUVs is induced by crystallization of the [N=P(OCH2CF3)2] blocks at the capsule wall of the GUVS, with the [N=PMePh] blocks at the corona. Higher degrees of crystallinity of the capsule wall are found in the bigger vesicles, which suggests that the crystallinity of the [N=P(OCH2CF3)2] block facilitates the formation of large vesicles. The GUVs are responsive to strong acids (HOTf) and, after selective protonation of the [N=PMePh] block, they undergo a morphological evolution to smaller spherical micelles in which the core and corona roles have been inverted. This morphological evolution is totally reversible by neutralization with a base (NEt3), which regenerates the original GUVs. The monitoring of this process by dynamic light scattering allowed a mechanism to to be proposed for this reversible morphological evolution in which the block copolymer 4 a and its protonated form 4 a(+) are intermediates. This opens a route to the design of reversibly responsive polymeric systems in organic solvents. This is the first reversibly responsive vesicle system to operate in organic media. PMID- 26880713 TI - Intramolecular charge transfer in aminobenzonitriles and tetrafluoro counterparts: fluorescence explained by competition between low-lying excited states and radiationless deactivation. Part I: A mechanistic overview of the parent system ABN. AB - Recent theoretical and experimental studies on the Intramolecular Charge Transfer (ICT) reaction of some members of the aminobezonitrile family (ABN) suggest the involvement of a (pi-sigma*) excited state (called ICT(CN) in this work) in the ICT process and the existence of a partially twisted ICT species that could be responsible for the anomalous fluorescence observed. These suggestions made us to revise our previous study on the photophysics of ABN and dimethyl-ABN (DMABN), based on the analysis of the potential energy surfaces of the low-lying excited states by means of ab initio calculations, using the CASSCF/CASPT2 protocol. We have first focused our attention to ABN. We have found that the (pi-sigma*) excited state can be in fact an intermediary state in the path to populate the ICT bright state, although its involvement in the process is not very probable. Our results suggest that the ICT most stable species is the twisted ICT(TICT) and that the partially twisted ICT minimum found in previous studies could be an artefact of the computational method. We have also found that radiationless deactivation is a competitive reaction that must be taken into account to explain the fluorescence patterns of these systems. To confirm our theories, we have also studied other systems with a similar architecture but with a very different luminescence behaviour: dimethyl-ABN, and the 2,3,4,5-tetrafluoro derivatives of ABN and DMABN (ABN-4F and DMABN-4F). The extension of the work and the different approaches in the study of the parent system and of the derivatives make the division of the work in two parts advisable. Part I collects the characterization of the minima and reaction paths connecting the critical points of the potential energy surfaces of the states involved in the ICT reaction of ABN. We have obtained, for the first time, the pathways of radiationless deactivation for this compound. We have also computed transition energies from the excited minima, to interpret the excited state absorption (ESA) spectra obtained experimentally. This information helps in the elucidation of the mechanism of ICT. In Part II we show an analoguous study for DMABN and ABN-4F and DMABN-4F and analyse and compare these results and those of Part I to explain different luminescence behaviours of the four systems studied. PMID- 26880714 TI - Guillain-Barre syndrome in the elderly. AB - The aim of the study was to analyze specific features of Guillain-Barre syndrome (GBS) in old people. The study included 403 GBS patients (62% young [<60 years], 35% young-old [60-80 years], and 3% old-old [>80 years]). Diagnosis of GBS was made according to the National Institute of Neurological Disorders and Stroke (NINDS criteria). Severe disability (GBS disability score of >3) at nadir was more common in old compared with young patients (p = 0.0001) as was mortality (9% vs. 2%, respectively). Acute motor and sensory axonal neuropathy and hyponatremia were more common in old compared with young patients (12% vs. 6% and 27% vs. 18%, respectively, p = 0.04). A positive history for malignancy was more than three times more common in old than young patients (11% vs. 3%, respectively, p = 0.01). Disability on nadir was similar in young-old and old-old subjects with disability on discharge being more severe in old-old (p = 0.04) suggesting slower recovery in this subgroup. Bulbar symptoms were more common in old-old compared with young-old (50% vs. 19%, respectively, p = 0.01). Comorbidities were present in virtually all old-old patients compared with 66% of young-old patients (p = 0.04). In conclusion, Elderly patients, and especially old-old patients, with GBS have more severe disease with slower recovery than do younger patients. PMID- 26880716 TI - Measuring Associations of the Department of Veterans Affairs' Suicide Prevention Campaign on the Use of Crisis Support Services. AB - Campaigns have become popular in public health approaches to suicide prevention; however, limited empirical investigation of their impact on behavior has been conducted. To address this gap, utilization patterns of crisis support services associated with the Department of Veterans Affairs' Veterans Crisis Line (VCL) suicide prevention campaign were examined. Daily call data for the National Suicide Prevention Lifeline, VCL, and 1-800-SUICIDE were modeled using a novel semi-varying coefficient method. Analyses reveal significant increases in call volume to both targeted and broad resources during the campaign. Findings underscore the need for further research to refine measurement of the effects of these suicide prevention efforts. PMID- 26880715 TI - Mutant KRAS Conversion of Conventional T Cells into Regulatory T Cells. AB - Constitutive activation of the KRAS oncogene in human malignancies is associated with aggressive tumor growth and poor prognosis. Similar to other oncogenes, KRAS acts in a cell-intrinsic manner to affect tumor growth or survival. However, we describe here a different, cell-extrinsic mechanism through which mutant KRAS contributes to tumor development. Tumor cells carrying mutated KRAS induced highly suppressive T cells, and silencing KRAS reversed this effect. Overexpression of the mutant KRAS(G12V)gene in wild-type KRAS tumor cells led to regulatory T-cell (Treg) induction. We also demonstrate that mutant KRAS induces the secretion of IL10 and transforming growth factor-beta1 (both required for Treg induction) by tumor cells through the activation of the MEK-ERK-AP1 pathway. Finally, we report that inhibition of KRAS reduces the infiltration of Tregs in KRAS-driven lung tumorigenesis even before tumor formation. This cell-extrinsic mechanism allows tumor cells harboring a mutant KRAS oncogene to escape immune recognition. Thus, an oncogene can promote tumor progression independent of its transforming activity by increasing the number and function of Tregs. This has a significant clinical potential, in which targeting KRAS and its downstream signaling pathways could be used as powerful immune modulators in cancer immunotherapy. PMID- 26880717 TI - Giardia and Cryptosporidium spp. dissemination during wastewater treatment and comparative detection via immunofluorescence assay (IFA), nested polymerase chain reaction (nested PCR) and loop mediated isothermal amplification (LAMP). AB - Environmental water samples from the Lower Rhine area in Germany were investigated via immunofluorescence assays (IFAs), nested polymerase chain reaction (nested PCR) and loop-mediated isothermal amplification (LAMP) to detect the presence of Giardia spp. (n=185) and Cryptosporidium spp. (n=227). The samples were concentrated through filtration or flocculation, and oocysts were purified via centrifugation through a sucrose density gradient. For all samples, IFA was performed first, followed by DNA extraction for the nested PCR and LAMP assays. Giardia cysts were detected in 105 samples (56.8%) by IFA, 62 samples (33.5%) by nested PCR and 79 samples (42.7%) by LAMP. Cryptosporidium spp. were detected in 69 samples (30.4%) by IFA, 95 samples (41.9%) by nested PCR and 99 samples (43.6%) by LAMP. According to these results, the three detection methods are complementary for monitoring Giardia and Cryptosporidium in environmental waters. PMID- 26880718 TI - Novel tubular constructs for urinary diversion: a biocompatibility study in pigs. AB - The use of bowel tissue for urinary diversion can be associated with severe complications, and regenerative medicine may circumvent this by providing an engineered conduit. In this study, a novel tubular construct was identified for this purpose. Three constructs (diameter 15 mm) were prepared from type I collagen and either (a) a semi-biodegradable Vypro II polymer (COL-Vypro), (b) a rapidly biodegradable Vicryl polymer (COL-Vicryl) or (c) an additional collagenous layer (COL-DUAL). After freezing, lyophilization and crosslinking, all constructs showed a porous structure with a two-fold higher strength for the polymer-containing constructs. These constructs were connected to full bladder defects of 11 female pigs and evaluated after 1 (n = 4) or 3 months (n = 5). With respect to surgical handling, the polymer-containing constructs were superior. All pigs voided normally without leakage and the survival rate was 82%. For the implanted COL-Vypro constructs (8/9), stone formation was observed. COL-DUAL and COL-Vicryl showed better biocompatibility and only small remnants were found 1 month post-implantation. Histological and immunohistochemical analysis showed the best regeneration for COL-Vicryl with respect to urothelium; muscle pedicles and elastin formation were best developed in the COL-Vicryl constructs. In this study, COL-Vicryl constructs were superior in both biocompatibility and bladder tissue regeneration and have high potential for artificial urinary diversions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26880721 TI - Influence of Equilibration Time in Solution on the Inclusion/Exclusion Topology Ratio of Host-Guest Complexes Probed by Ion Mobility and Collision-Induced Dissociation. AB - Host-guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion-mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host-guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas-phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision-induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process. PMID- 26880720 TI - Effective percutaneous "edge-to-edge" mitral valve repair with mitraclip in a patient with acute post-MI regurgitation not related to papillary muscle rupture. AB - A 65-year-old woman was admitted to our institution for rest dyspnea and hypotension. EKG showed sinus tachycardia with signs of infero-posterior STEMI. 2D-echocardiogram showed severe left ventricular systolic dysfunction with a- diskynesia of the inferior and posterior walls and severe functional mitral regurgitation (MR). The patient underwent urgent coronary angiography that showed 3-vessels disease with total occlusion of both first obtuse marginal (OM) branch of the left circumflex artery and right coronary artery (RCA) and critical stenosis of left anterior descending (LAD). Because of extremely high surgical risk, we performed a staged totally percoutaneous approach. First, we reopened the presumed culprit vessels (RCA and OM) and then, after 48 hr, we performed angioplasty of the LAD. Since revascularization provided no significant improvement in respiratory and hemodynamic parameters we performed a percutaneous mitral repair with Mitraclip. MR grade was reduced from severe to trivial with rapid improvement of the respiratory and hemodynamic parameters. The post procedural course was uneventful and the patient was discharged 7 days later. At the 30-day and 6-month follow-up the patient remained asymptomatic in NYHA I functional class with no recurrence of MR. Acute MR due to post-AMI mechanical complications is generally considered a contraindication to MitraClip implantation for several reasons. However, the present report shows that, in selected cases, the Mitraclip system may be successfully used to reduce the severity of acute MR secondary to AMI and may allow to reverse cardiogenic shock and/or refractory pulmonary congestion related to the acute regurgitation. (c) 2016 Wiley Periodicals, Inc. PMID- 26880719 TI - Glycosylation status of serum immunoglobulin G in patients with prostate diseases. AB - Occurrences of high values in patients with benign prostate disease and low values in patients with highly suspicious cancer have diminished the trustworthiness of prostate-specific antigen as an early diagnostic marker of prostate cancer. In the search for other complimentary markers, we focused on serum IgG from patients with prostate diseases as well as normal subjects. IgG purified from the sera of normal control subjects and patients with prostate diseases, was digested with peptide N-glycanase. Released glycans were quantified using MALDI-time of flight mass spectrometry. We report that N-linked (N acetylhexosamine)2 (deoxyhexose)(mannose)3 (N-acetylglucosamine)2 was significantly increased in the IgG heavy chains of patients with prostate cancer compared with that of either benign prostatic disease patients or healthy subjects, whereas (hexose)(N-acetylhexosamine)2 (deoxyhexose)(mannose)3 (N acetylglucosamine)2 was more abundant in the heavy chains of healthy subjects and benign prostatic disease patients. Thus, an absence of the terminal hexose of N linked glycans has been closely connected to the progression of prostate cancer. Furthermore, surface plasmon resonance analyses have revealed that IgG from patients with prostate cancer has a decreased binding for Sambucus nigra lectin, compared with that from the benign prostatic disease patients or from normal subjects, suggesting lower levels of (N-acetylneuraminic acid)(alpha2 6)galactose/N-acetylgalactosamine groups in the N-linked glycans of patient IgG. Meanwhile, wheat germ agglutinin binding to IgG of the cancer group was significantly larger than that for the benign prostatic disease group but smaller than that for normal subjects. Our study indicates that the glycosylation changes in IgG can become useful diagnostic parameters for prostate cancer. PMID- 26880722 TI - Vein of Galen aneurysmal malformation-clinical and angiographic spectrum with management perspective: an institutional experience. AB - BACKGROUND AND PURPOSE: Vein of Galen aneurysmal malformation (VGAM) is a rare developmental intracranial vascular malformation. We analyzed the clinical presentations, imaging findings, angioarchitecture, management options, and outcome in a demographically heterogeneous set of VGAM patients. METHODS: We retrospectively analyzed cases of VGAM from our departmental archive collected between 1988 and January 2015. Demographic, clinical, therapeutic, and follow-up details were obtained for each patient from the available records. RESULTS: We identified 36 patients with VGAM including 6 neonates, 18 infants, 7 children aged 2-10 years, and 5 adults. Macrocrania was the commonest presenting feature. Type of fistulae was mural in 14 and choroidal in 18 patients while 4 had a thrombosed sac at presentation. In 3 cases the dilated venous sac had connection with the deep venous system. Bilateral jugular atresia and stenosis were seen in 9 and 6 patients, respectively. Giant venous sac (>4 cm) was significantly correlated with mural type (p=0.0001). Dural arterial recruitment was seen in 4 patients including 3 adults. Among the 23 patients treated by endovascular means, 14 had a good outcome, 5 had a poor outcome, and 4 died. A significant correlation was noted between jugular atresia and poor outcome (p=0.003). CONCLUSIONS: We encountered a wide range of demographic, clinical, and angiographic features in VGAM. Mural type malformations were associated with giant venous sacs. Good outcome after embolization was seen in selected neonates and in most of the infants, children, and adults. Jugular atresia was significantly associated with poor outcome. PMID- 26880723 TI - Bilateral inferior petrosal sinus sampling: experience in 327 patients. AB - OBJECTIVE: To describe findings and outcomes of 331 bilateral inferior petrosal sinus sampling (BIPSS) procedures performed in 327 patients evaluated for Cushing disease (CD). MATERIALS AND METHODS: The radiology department's electronic database was searched to identify all BIPSS procedures (1990-2013). Electronic medical records were used to identify demographics, laboratory, procedural, surgical and pathologic findings. RESULTS: A total of 331 BIPSS procedures were performed in 327 patients (254 F, 73 M), mean age 41 (range 7-81) years. The overall technical success rate was 88% for bilateral cannulation, though nearly two-thirds of the technical failures had unilateral sampling that diagnosed CD. Of the 331 BIPSS procedures, 40 were performed without, and 291 with stimulation by Acthrel or desmopressin. Sensitivity was 89-94% for unstimulated BIPSS, 96% for stimulated BIPSS, and 77% for MRI. BIPSS lateralization was accurate in about half of patients, compared with 75% accuracy for MRI. Mean inferior petrosal sinus (IPS):peripheral adrenocorticotropic hormone ratio was 17.3 (SE 1.8) at baseline, and 99.2 (SE 14.8) at 3 min, with decreasing values over time. All patients with follow-up after surgical resection for centralizing BIPSS were reported to be cured, with cortisol levels significantly decreased from 19 to 4 MUg/dL (p<0.0001). Complications from BIPSS were rare, including groin hematoma (2.5%), but no thromboembolic complications were seen. CONCLUSIONS: BIPSS remains the 'gold standard' for diagnosing CD. Stimulation with Acthrel or desmopressin is key to increasing specificity. When only one IPS can be successfully cannulated, results may still be diagnostic. BIPSS findings cannot be used to accurately lateralize lesions within the pituitary. PMID- 26880724 TI - Computational fluid dynamics analysis of flow reduction induced by flow-diverting stents in intracranial aneurysms: a patient-unspecific hemodynamics change perspective. AB - BACKGROUND AND PURPOSE: Flow-diverter stents (FDSs) have been used effectively to treat large neck and complex saccular aneurysms on the anterior carotid circulation. Intra-aneurysmal flow reduction induces progressive aneurysm thrombosis in most patients. Understanding the degree of flow modification necessary to induce complete aneurysm occlusion among patients with considerable hemodynamics variability may be important for treatment planning. MATERIALS AND METHODS: Patients with incidental intracranial saccular aneurysms who underwent FDS endovascular procedures were included and studied for a 12 months' follow-up period. We used computational fluid dynamics on patient-specific geometries from 3D rotational angiography without and with virtual stent placement and thus compared intra-aneurysmal hemodynamic problems. Receiver operating characteristic analysis was used to estimate the stent:no-stent minimum hemodynamic ratio thresholds that significantly (p<=0.05) determined the condition necessary for long-term (12 months) aneurysm occlusion. RESULTS: We included 12 consecutive patients with sidewall aneurysms located in the internal carotid or vertebral artery. The measured porosity of the 12 deployed virtual FDSs was 83+/-3% (mean+/ SD). Nine aneurysms were occluded during the 12 months' follow-up, whereas three were not. A significant (p=0.05) area under the curve (AUC) was found for spatiotemporal mean velocity reduction in the aneurysms: AUC=0.889+/-0.113 (mean+/-SD) corresponding to a minimum velocity reduction threshold of 0.353 for occlusion to occur. The 95% CI of the AUC was 0.66 to 1.00. The sensitivity and specificity of the method were ~99% and ~67%, respectively. For both wall shear stress and pressure reductions in aneurysms no thresholds could be determined: AUC=0.63+/-0.16 (p=0.518) and 0.67+/-0.165 (p=0.405), respectively. CONCLUSIONS: For successful FDS treatment the post-stent average velocity in sidewall intracranial aneurysms must be reduced by at least one-third from the initial pre stent conditions. PMID- 26880725 TI - A Hospital-Based Interdisciplinary Model for Increasing Nurses' Engagement in Legislative Advocacy. AB - The Legislative Action Interest Group (LAIG) is a hospital-based health policy forum that engages nurses in exploring clinical implications of existing and pending health policies and regulations, while also creating a feedback loop to inform policy makers about the realities nursing practice and patient care. The LAIG is a collaborative effort between the hospital's Department of Nursing and Patient Care Services and the Office of Government Relations at an academic children's hospital. Nurses participating in the LAIG forums build a working knowledge of health policy and can articulate the practice realities for policy decision makers. Participants explore the political context of nursing and pediatric policies while learning about the state legislative process. Beyond the monthly meetings, members build policy advocacy skills and have testified at public hearings, met with state and federal legislators, and led tours for policy makers through the hospital. The LAIG model also benefits the government relations staff by providing time for them to discuss clinical implications of pending policies with nurses from practice settings in the hospital. Forum discussions enhance the ability of the hospital's lobbyists to articulate practice implications of health policy to lawmakers. This case study, describing the origin, structure, operations, and outcomes of the LAIG model, and has implications for nurses in hospitals and academic settings who are interested in engaging in policy work. Opportunities to research the sustainability, replicability, and patient-centered outcomes of LAIG forums represent future work needed to advance nursing's participation in policy. PMID- 26880726 TI - Analysis of Kentucky's Law Protecting the Rights of Schoolchildren With Type 1 Diabetes Mellitus: Application of Kingdon's Policy Stream Model. AB - Type 1 diabetes mellitus is a chronic, life-threatening disorder that affects children of all ages. Based on data from 2008 to 2009, the Centers for Disease Control and Prevention estimates that in the United States, 191,986 youth younger than age 20 require treatment for diabetes, the majority of whom have Type 1 diabetes mellitus. These children require assistance with counting carbohydrates, testing blood glucose, and administering subcutaneous insulin. Establishing appropriate diabetes care models in schools is necessary for children's immediate safety, long-term well-being, and optimal academic performance. Kentucky House Bill 98 was passed by the state legislature in 2014 to allow unlicensed school personnel to assist children with diabetes care. The purpose of this article is to apply Kingdon's policy streams model to an analysis of a state policy allowing unlicensed school personnel to assist children with diabetes care. The article covers potential policy alternatives and concludes with a discussion of implications for nursing practice. PMID- 26880727 TI - ZnO Nanowire-Based Corona Discharge Devices Operated Under Hundreds of Volts. AB - Minimizing the voltage of corona discharges, especially when using nanomaterials, has been of great interest in the past decade or so. In this paper, we report a new corona discharge device by using ZnO nanowires operated in atmospheric air to realize continuous corona discharge excited by hundreds of volts. ZnO nanowires were synthesized on microelectrodes using electric-field-assisted wet chemical method, and a thin tungsten film was deposited on the microchip to enhance discharging performance. The testing results showed that the corona inception voltages were minimized greatly by using nanowires compared to conventional dischargers as a result of the local field enhancement of nanowires. The corona could be continuously generated and self-sustaining. It was proved that the law of corona inception voltage obeyed the conventional Peek's breakdown criterion. An optimal thickness of tungsten film coated over ZnO nanowires was figured out to obtain the lowest corona inception voltage. The ion concentration of the nanowire-based discharger attained 10(17)/m(3) orders of magnitude, which is practicable for most discharging applications. PMID- 26880728 TI - Enhanced Photocatalytic Performance of Luminescent g-C3N4 Photocatalyst in Darkroom. AB - Graphitic-C3N4(g-C3N4), a low-cost visible-light-driven photocatalyst, was used for the photocatalytic oxidation of aqueous methylene blue (MB) in the dark with Sr4Al14O25:(Eu,Dy) assistance. The Sr4Al14O25:(Eu,Dy)/g-C3N4 photocatalysts were fabricated through the ultrasonic dispersion method. The commercial Sr4Al14O25:(Eu,Dy) phosphor was used as a long afterglow supplier for exciting g C3N4 in the dark. The results demonstrated that the metal-free g-C3N4 photocatalyst could use the eye-visible long afterglow to photocatalytically decompose MB dyes in the dark. This work may expand the appealing application of g-C3N4 for the environmental cleanup. PMID- 26880729 TI - The Effect of Pre-sowing Seed Treatment with Metal Nanoparticles on the Formation of the Defensive Reaction of Wheat Seedlings Infected with the Eyespot Causal Agent. AB - The paper presents research data of lipid peroxidation and lectin activity in wheat seedlings at seed treatment with solution of metal nanoparticles (Zn, Ag, Fe, Mn, Cu) and sole solution of copper nanoparticles under the high pathogen infection background of Pseudocercosporella herpotrichoides (Fron) Deighton (synonym: Oculimacula yallundae (Wallwork & Sponer) Crous & W. Gams). It was shown that investigated nonionic colloidal solutions of biogenic metals have the antioxidant effect through the inhibition of the synthesis of lipid peroxidation products. The increase of lectin activity levels during the early plants ontogenesis stages was observed in wheat seedlings infected with pathogen pre treated with the mixture of metal nanoparticles. PMID- 26880730 TI - Influence of Treatment Temperature on Microstructure and Properties of YSZ-NiO Anode Materials. AB - The cyclic treatment technique (redox cycling) comprising stages of material exposition in reducing and oxidizing high-temperature environments and intermediate degassing between these stages has been developed to improve the structural integrity of YSZ-NiO ceramic anode substrates for solid oxide fuel cells. A series of specimens were singly reduced in a hydrogenous environment (the Ar-5 vol% N2 mixture or hydrogen of 99.99 vol% H2 purity) under the pressure of 0.15 MPa or subjected to redox cycling at 600 or 800 degrees C. The influence of redox cycling at the treatment temperatures of 600 and 800 degrees C on the structure, strength and electrical conductivity of the material has been analysed. Using the treatment temperature 600 degrees C, a structure providing improved physical and mechanical properties of the material was formed. However, at the treatment temperature 800 degrees C, an anode structure with an array of microcracks was formed that significantly reduced the strength and electrical conductivity of the material. PMID- 26880731 TI - Involvement of sensory innervation in the skin of SOD1(G93A) ALS mice. AB - Sensory alterations have been described in both amyotrophic lateral sclerosis (ALS) patients and mouse models. While involvement of intraepidermal and subepidermal axons has been shown in skin biopsies of ALS patients, it is unclear if the SOD1(G93A) mouse presents similar alterations. We analyzed the epidermal and dermal innervation, based on PGP9.5 immunostaining, of SOD1(G93A) mice at different stages. The results showed a marked reduction of intraepidermal nerve fibers, Meissner's corpuscles, and subepidermal nerve density already at 4 weeks. This loss of innervation progressed over time. Dermal axonal density decreased at a later stage of the disease. There was a gradient of axonal loss, with a more severe decline in the epidermis compared with deeper structures, indicating a distal axonal neuropathy as the mechanism of degeneration. These findings suggest that the analysis of the cutaneous sensory innervation may be an accessible and useful tool to assess the neurodegeneration process in motoneuron diseases. PMID- 26880732 TI - Cost-effectiveness of risk-based screening for cervical length to prevent preterm birth. AB - BACKGROUND: Despite much debate, there is no consensus on whether women without a history of prior spontaneous preterm birth should receive universal cervical length screening. Risk-based screening has been proposed as an alternative to universal cervical length measurement and may represent a more cost-effective approach to preterm birth prevention. OBJECTIVE: We sought to evaluate the cost effectiveness of risk-based screening compared to universal cervical length screening or no screening for preterm birth prevention in low-risk women. STUDY DESIGN: A decision analytic model compared the cost and effectiveness of 3 cervical length screening strategies in a population of women with no prior preterm birth. Risk-based screening, universal screening, and no screening were compared using cost, probability, and utility estimates derived from the existing literature and the incremental cost-effectiveness ratios for each strategy were calculated. RESULTS: In the base-case analysis, risk-based screening and universal screening were more effective and less costly than no screening. In comparison to the risk-based strategy, universal screening of the United States population of women without a prior preterm birth (N = 3.5 million annually) would result in 2.19 million more transvaginal ultrasounds, 11,027 more women treated with vaginal progesterone, 913 fewer preterm births <35 weeks gestational age, and 63 fewer neonatal deaths at an additional cost of $51,936,699 annually. Despite costing more, the additional health benefits of universal screening resulted in that strategy being more cost-effective than risk-based screening, with an incremental cost-effectiveness ratio of $21,144 per quality-adjusted life year. CONCLUSION: In women without a prior spontaneous preterm birth, universal cervical length screening is cost-effective in comparison to both risk-based screening and no screening. PMID- 26880733 TI - The "occiput-spine angle": a new sonographic index of fetal head deflexion during the first stage of labor. AB - BACKGROUND: Fetal head "attitude" (relationship of fetal head to spine) in the first stage of labor may have a substantial impact on labor outcome. The diagnosis of fetal head deflexion traditionally is based on digital examination in labor, although the use of ultrasound to support clinical diagnosis has been recently reported. OBJECTIVES: The aims of this study were: (1) to quantify the degree of fetal head deflection via the use of sonography during the first stage of labor; and (2) to determine whether a parameter derived from ultrasound examination (the occiput-spine angle) has a relationship with the course and outcome of labor. STUDY DESIGN: This was a prospective multicentric, cross sectional study conducted at the Maternity Unit of the University of Bologna and Parma from January 2014 to April 2015. A nonconsecutive series of women with uncomplicated singleton pregnancies at term gestation (37 weeks or more) were submitted to transabdominal ultrasound during the first stage of labor. If fetal position was occiput anterior or transverse, the angle between the fetal occiput and the cervical spine (the occiput-spine angle) was sonographically obtained on the sagittal plane. The measurements of the occiput spine-angle were performed offline by 2 operators who were blinded to the labor outcome. The intra- and interobserver reproducibility and the correlation between the occiput-spine angle and the mode of delivery were evaluated. RESULTS: A total of 108 pregnant women were recruited, 79 of which underwent a spontaneous vaginal delivery and 29 were submitted to obstetric intervention (19 cesarean delivery and 10 instrumental vaginal deliveries). The mean value of the occiput-spine angle measured in the active phase of the first stage was 126 degrees +/- 9.8 degrees (SD). The occiput-spine angle measurement showed a very good intraobserver (r = 0.86; 95% confidence interval [95% CI] 0.80-0.90) and a fair-to-good interobserver (r = 0.64; 95% CI 0.51-0.74) agreement. The occiput-spine angle was significantly narrower in women who underwent obstetric intervention (cesarean or vacuum delivery) due to labor arrest (121 degrees +/- 10.5 degrees vs 127 degrees +/- 9.4 degrees , P = .03). Multivariable logistic regression analysis showed that narrow occiput-spine angle values (OR 1.08; 95% CI 1.00-1.16; P = .04) and nulliparity (OR 16.06; 95% CI 1.71-150.65; P = .02) were independent risk factors for operative delivery. A larger occiput-spine angle width (i.e., >125 degrees ) showed to be significantly associated with a shorter duration of labor (hazard ratio = 1.62; 95% CI 1.07-2.45; P = .02). CONCLUSION: We described herein the "occiput-spine angle," a new sonographic parameter to assess fetal head deflection during labor. Fetuses with smaller occiput-spine angle (<125 degrees ) are at increased risk for operative delivery. PMID- 26880734 TI - Identifying late-onset fetal growth restriction by measuring circulating placental RNA in the maternal blood at 28 weeks' gestation. AB - BACKGROUND: Late-onset fetal growth restriction (FGR) is often undetected prior to birth, which puts the fetus at increased risk of adverse perinatal outcomes including stillbirth. OBJECTIVE: Measuring RNA circulating in the maternal blood may provide a noninvasive insight into placental function. We examined whether measuring RNA in the maternal blood at 26-30 weeks' gestation can identify pregnancies at risk of late-onset FGR. We focused on RNA highly expressed in placenta, which we termed "placental-specific genes." STUDY DESIGN: This was a case-control study nested within a prospective cohort of 600 women recruited at 26-30 weeks' gestation. The circulating placental transcriptome in maternal blood was compared between women with late-onset FGR (<5th centile at >36+6 weeks) and gestation-matched well-grown controls (20-95th centile) using microarray (n = 12). TaqMan low-density arrays, reverse transcription-polymerase chain reaction (PCR), and digital PCR were used to validate the microarray findings (FGR n = 40, controls n = 80). RESULTS: Forty women developed late-onset FGR (birthweight 2574 +/- 338 g, 2nd centile) and were matched to 80 well-grown controls (birthweight 3415 +/- 339 g, 53rd centile, P < .05). Operative delivery and neonatal admission were higher in the FGR cohort (45% vs 23%, P < .05). Messenger RNA coding 137 placental-specific genes was detected in the maternal blood and 37 were differentially expressed in late-onset FGR. Seven were significantly dysregulated with PCR validation (P < .05). Activating transcription factor-3 messenger RNA transcripts were the most promising single biomarker at 26-30 weeks: they were increased in fetuses destined to be born FGR at term (2.1-fold vs well grown at term, P < .001) and correlated with the severity of FGR. Combining biomarkers improved prediction of severe late-onset FGR (area under the curve, 0.88; 95% CI 0.80-0.97). A multimarker gene expression score had a sensitivity of 79%, a specificity of 88%, and a positive likelihood ratio of 6.2 for subsequent delivery of a baby <3rd centile at term. CONCLUSION: A unique placental transcriptome is detectable in maternal blood at 26-30 weeks' gestation in pregnancies destined to develop late-onset FGR. Circulating placental RNA may therefore be a promising noninvasive test to identify pregnancies at risk of developing FGR at term. PMID- 26880736 TI - US term stillbirth rates and the 39-week rule: a cause for concern? AB - BACKGROUND: More than a decade ago an obstetric directive called "the 39-week rule" sought to limit "elective" delivery, via labor induction or cesarean delivery, before 39 weeks 0 days of gestation. In 2010 the 39-week rule became a formal quality measure in the United States. The progressive adherence to the 39 week rule throughout the United States has caused a well-documented, progressive reduction in the proportion of term deliveries occurring during the early-term period. Because of the known association between increasing gestational age during the term period and increasing cumulative risk of stillbirth, however, there have been published concerns that the 39-week rule-by increasing the gestational age of delivery for a substantial number of pregnancies-might increase the rate of term stillbirth within the United States. Although adherence to the 39-week rule is assumed to be beneficial, its actual impact on the US rate of term stillbirth in the years since 2010 is unknown. OBJECTIVE: To determine whether the adoption of the 39-week rule was associated with an increased rate of term stillbirth in the United States. STUDY DESIGN: Sequential ecological study, based on state data, of US term deliveries that occurred during a 7-year period bounded by 2007 and 2013. The patterns of the timing of both term childbirth and term stillbirth were determined for each state and for the United States as a whole. RESULTS: A total of 46 usable datasets were obtained (45 states and the District of Columbia). During the 7-year period, there was a continuous reduction in all geographic entities in the proportion of term deliveries that occurred before 39 weeks of gestation. The overall rate of term stillbirth, when we compared 2007-2009 with 2011-2013, increased significantly (1.103/1000 vs 1.177/1000, RR 1.067, 95% confidence interval 1.038-1.096). Furthermore, during the 7-year period, the increase in the rate of US term stillbirth appeared to be continuous (estimated slope: 0.0186/1000/year, 95% confidence interval 0.002 0.035). Assuming 3.5 million term US births per year, and given 6 yearly "intervals" with this rate increase, it is possible that more than 335 additional term stillbirths occurred in the United States in 2013 as compared with 2007. In addition, during the 7-year period, there was a progressive shift in the timing of delivery from the 40th week to the 39th week. Absent this confounding factor, the magnitude of association between the adoption of the 39-week rule and the increase in rate of term stillbirth might have been greater. CONCLUSIONS: Between 2007 and 2013 in the United States, the adoption of the 39-week rule caused a progressive reduction in the proportion of term births occurring before the 39th week of gestation. During the same interval the United States experienced a significant increase in its rate of term stillbirth. This study raises the possibility that the 39-week rule may be causing unintended harm. Additional studies of the actual impact of the adoption of the 39-week rule on major childbirth outcomes are urgently needed. Pressures to enforce the 39-week rule should be reconsidered pending the findings of such studies. PMID- 26880735 TI - Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR). AB - BACKGROUND: The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. OBJECTIVE: In the current study, we sought to characterize the impact of the intrauterine growth restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. STUDY DESIGN: F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. RESULTS: Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. CONCLUSION: Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome. PMID- 26880737 TI - Determining performance characteristics of an NGS-based HLA typing method for clinical applications. AB - This study presents performance specifications of an in-house developed human leukocyte antigen (HLA) typing assay using next-generation sequencing (NGS) on the Illumina MiSeq platform. A total of 253 samples, previously characterized for HLA-A, -B, -C, -DRB1 and -DQB1 were included in this study, which were typed at high-resolution using a combination of Sanger sequencing, sequence-specific primer (SSP) and sequence-specific oligonucleotide probe (SSOP) technologies and recorded at the two-field level. Samples were selected with alleles that cover a high percentage of HLA specificities in each of five different race/ethnic groups: European, African-American, Asian Pacific Islander, Hispanic and Native American. Sequencing data were analyzed by two software programs, Omixon's target and GenDx's NGSengine. A number of metrics including allele balance, sensitivity, specificity, precision, accuracy and remaining ambiguity were assessed. Data analyzed by the two software systems are shown independently. The majority of alleles were identical in the exonic sequences (third field) with both programs for HLA-A, -B, -C and -DQB1 in 97.7% of allele determinations. Among the remaining discrepant genotype calls at least one of the analysis programs agreed with the reference typing. Upon additional manual analysis 100% of the 2530 alleles were concordant with the reference HLA genotypes; the remaining ambiguities did not exceed 0.8%. The results demonstrate the feasibility and significant benefit of HLA typing by NGS as this technology is highly accurate, eliminates virtually all ambiguities, provides complete sequencing information for the length of the HLA gene and forms the basis for utilizing a single methodology for HLA typing in the immunogenetics labs. PMID- 26880738 TI - Creating a Community of Practice to Prevent Suicide Through Multiple Channels: Describing the Theoretical Foundations and Structured Learning of PC CARES. AB - It is critical to develop practical, effective, ecological, and decolonizing approaches to indigenous suicide prevention and health promotion for the North American communities. The youth suicide rates in predominantly indigenous small, rural, and remote Northern communities are unacceptably high. This health disparity, however, is fairly recent, occurring over the last 50 to 100 years as communities experienced forced social, economic, and political change and intergenerational trauma. These conditions increase suicide risk and can reduce people's access to shared protective factors and processes. In this context, it is imperative that suicide prevention includes--at its heart--decolonization, while also utilizing the "best practices" from research to effectively address the issue from multiple levels. This article describes such an approach: Promoting Community Conversations About Research to End Suicide (PC CARES). PC CARES uses popular education strategies to build a "community of practice" among local and regional service providers, friends, and families that fosters personal and collective learning about suicide prevention in order to spur practical action on multiple levels to prevent suicide and promote health. This article will discuss the theoretical underpinnings of the community intervention and describe the form that PC CARES takes to structure ongoing dialogue, learning, solidarity, and multilevel mobilization for suicide prevention. PMID- 26880739 TI - Role of SFRP1 in NPC Metastasis-Response. PMID- 26880741 TI - Jerome Harold Kay (17 March 1921-14 August 2015): a great innovator in cardiac surgery. PMID- 26880740 TI - Role of SFRP1 in NPC Metastasis-Letter. PMID- 26880742 TI - Cadaveric validation study of computational fluid dynamics model of sinus irrigations before and after sinus surgery. AB - BACKGROUND: Investigations into the distribution of sinus irrigations have been limited by labor-intensive methodologies that do not capture the full dynamics of irrigation flow. The purpose of this study was to validate the accuracy of a computational fluid dynamics (CFD) model for sinonasal irrigations through a cadaveric experiment. METHODS: Endoscopic sinus surgery was performed on 2 fresh cadavers to open all 8 sinuses, including a Draf III procedure for cadaver 1, and Draf IIb frontal sinusotomies for cadaver 2. Computed tomography maxillofacial scans were obtained preoperatively and postoperatively, from which CFD models were created. Blue-dyed saline in a 240-mL squeeze bottle was used to irrigate cadaver sinuses at 60 mL/second (120 mL per side, over 2 seconds). These parameters were replicated in CFD simulations. Endoscopes were placed through trephinations drilled through the anterior walls of the maxillary and frontal sinuses, and sphenoid roofs. Irrigation flow into the maxillary, frontal, and sphenoid sinuses was graded both ipsilateral and contralateral to the side of nasal irrigation, and then compared with the CFD simulations. RESULTS: In both cadavers, preoperative and postoperative irrigation flow into maxillary, frontal, and sphenoid sinuses matched extremely well when comparing the CFD models and cadaver endoscopic videos. For cadaver 1, there was 100% concordance between the CFD model and cadaver videos, and 83% concordance for cadaver 2. CONCLUSION: This cadaveric experiment provided potential validation of the CFD model for simulating saline irrigation flow into the maxillary, frontal, and sphenoid sinuses before and after sinus surgery. PMID- 26880743 TI - Tobacco price increase and smoking behaviour changes in various subgroups: a nationwide longitudinal 7-year follow-up study among a middle-aged Japanese population. AB - OBJECTIVE: Few longitudinal studies have examined the effect of tobacco price increase on both cessation among smokers and relapse among quitters. Our objective was to investigate the differential impact of the tobacco price increase on the changes in smoking status in the total population and various subgroups. METHODS: We analysed data from a Japanese nationally representative longitudinal study of 30 773 individuals aged 50-59 years (weighted sum of discrete-time number = 215 411) with smoking information, using inverse probability weighting to account for non-response at follow-up. Generalised estimating equation models were used to calculate the odds ratios (ORs) for smoking behavioural changes (cessation among smokers and relapse among quitters), using discrete-time design. Stratified analyses were conducted according to demographic, socioeconomic and health behavioural characteristics. RESULTS: From 2005 to 2012, current smoker prevalence among the middle-aged Japanese population decreased from 30.5% to 24.3%. Of all the factors surveyed, only the tobacco price increase in 2010 (up by 37%, the highest increase during the period) was significantly associated with both cessation among smokers (OR 2.14, 95% confidence interval 1.90 to 2.41) and prevention of relapse among quitters (0.60, 0.46 to 0.77). Regarding the subgroup analysis, the tobacco price increase was associated with a significant reduction in relapse in the lowest income, recent quitters and very poor health subgroups. However, different associations were observed for cessation; a significant association between price increase and cessation was observed among all subgroups except for the heavy smoker and recently unemployed subgroups. CONCLUSIONS: We confirmed that the tobacco price rise was associated with increasing cessation and decreasing relapse concurrently. Furthermore, this price rise was associated with favourable smoking changes in nearly all population subgroups; a large differential impact was not observed across the various subgroups. PMID- 26880744 TI - Contemporary impact of tobacco use on periodontal disease in the USA. PMID- 26880745 TI - Electronic cigarette use and indoor air quality in a natural setting. AB - INTRODUCTION: Secondhand smoke (SHS) from combustible cigarettes causes numerous diseases. Policies have been developed to prevent SHS exposure from indoor cigarette use to reduce health risks to non-smokers. However, fewer policies have been implemented to deter electronic cigarette (ECIG) use indoors, and limited research has examined the impact of secondhand exposure to ECIG aerosol. METHODS: Indoor air quality was measured at a 2-day ECIG event held in a large room at a hotel. Fine particulate matter (PM) was measured using 2 devices that measured concentrations of PM 2.5 MUm aerodynamic diameter or smaller (PM2.5). Measurements were taken before the event, over 2 days when the event was ongoing, and the day after the event. PM2.5 measurements were also taken from the restaurant at the hotel hosting the event and a restaurant at a nearby hotel. RESULTS: During 6 time points when the event was ongoing, between 59 and 86 active ECIG users were present in the event room (room volume=4023 m3). While the event was ongoing, median PM2.5 concentrations in the event room increased from a baseline of 1.92-3.20 MUg/m3 to concentrations that ranged from 311.68 MUg/m3 (IQR 253.44-411.84 MUg/m3) to 818.88 MUg/m3 (IQR 760.64-975.04 MUg/m3). CONCLUSIONS: PM2.5 concentrations observed at the ECIG event were higher than concentrations reported previously in hookah cafes and bars that allow cigarette smoking. This study indicates that indoor ECIG use exposes non-users to secondhand ECIG aerosol. Regulatory bodies should consider establishing policies that prohibit ECIG use anywhere combustible cigarette use is prohibited. PMID- 26880747 TI - Analysis of root growth from a phenotyping data set using a density-based model. AB - Major research efforts are targeting the improved performance of root systems for more efficient use of water and nutrients by crops. However, characterizing root system architecture (RSA) is challenging, because roots are difficult objects to observe and analyse. A model-based analysis of RSA traits from phenotyping image data is presented. The model can successfully back-calculate growth parameters without the need to measure individual roots. The mathematical model uses partial differential equations to describe root system development. Methods based on kernel estimators were used to quantify root density distributions from experimental image data, and different optimization approaches to parameterize the model were tested. The model was tested on root images of a set of 89 Brassica rapa L. individuals of the same genotype grown for 14 d after sowing on blue filter paper. Optimized root growth parameters enabled the final (modelled) length of the main root axes to be matched within 1% of their mean values observed in experiments. Parameterized values for elongation rates were within +/ 4% of the values measured directly on images. Future work should investigate the time dependency of growth parameters using time-lapse image data. The approach is a potentially powerful quantitative technique for identifying crop genotypes with more efficient root systems, using (even incomplete) data from high-throughput phenotyping systems. PMID- 26880746 TI - Selective Targeting of Heme Protein in Cytochrome P450 and Nitric Oxide Synthase by Diphenyleneiodonium. AB - Cytochrome P450 (CYP) enzymes mediate mixed-function oxidation reactions important in drug metabolism. The aromatic heterocyclic cation, diphenyleneiodonium (DPI), binds flavin in cytochrome P450 reductase and inhibits CYP-mediated activity. DPI also inhibits CYP by directly interacting with heme. Herein, we report that DPI effectively inhibits a number of CYP-related monooxygenase reactions including NADPH oxidase, a microsomal enzyme activity that generates hydrogen peroxide in the absence of metabolizing substrates. Inhibition of monooxygenase by DPI was time and concentration dependent with IC50's ranging from 0.06 to 1.9 MUM. Higher (4.6-23.9 MUM), but not lower (0.06 1.9 MUM), concentrations of DPI inhibited electron flow via cytochrome P450 reductase, as measured by its ability to reduce cytochrome c and mediate quinone redox cycling. Similar results were observed with inducible nitric oxide synthase (iNOS), an enzyme containing a C-terminal reductase domain homologous to cytochrome P450 reductase that mediates reduction of cytochrome c, and an N terminal heme-thiolate oxygenase domain mediating nitric oxide production. Significantly greater concentrations of DPI were required to inhibit cytochrome c reduction by iNOS (IC50 = 3.5 uM) than nitric oxide production (IC50 = 0.16 uM). Difference spectra of liver microsomes, recombinant CYPs, and iNOS demonstrated that DPI altered heme-carbon monoxide interactions. In the presence of NADPH, DPI treatment of microsomes and iNOS yielded a type II spectral shift. These data indicate that DPI interacts with both flavin and heme in CYPs and iNOS. Increased sensitivity for inhibition of CYP-mediated metabolism and nitric oxide production by iNOS indicates that DPI targets heme moieties within the enzymes. PMID- 26880748 TI - Two major quantitative trait loci controlling the number of seminal roots in maize co-map with the root developmental genes rtcs and rum1. AB - The genetic dissection of root architecture and functions allows for a more effective and informed design of novel root ideotypes and paves the way to evaluate their effects on crop resilience to a number of abiotic stresses. In maize, limited attention has been devoted to the genetic analysis of root architecture diversity at the early stage. The difference in embryonic (including seminal and primary) root architecture between the maize reference line B73 (which mostly develops three seminal roots) and the landrace Gaspe Flint (with virtually no seminal roots) was genetically dissected using a collection of introgression lines grown in paper rolls and pots. Quantitative trait locus (QTL) analysis identified three QTLs controlling seminal root number (SRN) on chromosome bins 1.02, 3.07, and 8.04-8.05, which collectively explained 66% of the phenotypic variation. In all three cases, Gaspe Flint contributed the allele for lower SRN. Primary root dry weight was negatively correlated with SRN (r= 0.52), and QTLs for primary root size co-mapped with SRN QTLs, suggesting a pleiotropic effect of SRN QTLs on the primary root, most probably caused by competition for seed resources. Interestingly, two out of three SRN QTLs co mapped with the only two known maize genes (rtcs and rum1) affecting the number of seminal roots. The strong additive effect of the three QTLs and the development of near isogenic lines for each QTL in the elite B73 background provide unique opportunities to characterize functionally the genes involved in root development and to evaluate how root architecture affects seedling establishment, early development, and eventually yield in maize. PMID- 26880750 TI - Introduction of a simple guideline to improve neurological assessment in paediatric patients presenting with upper limb fractures. AB - BACKGROUND: Neurological examination in children presenting with upper limb fractures is often poorly performed in the Emergency Department (ED). We aimed to assess the improvement in documented neurological examination for children presenting with upper limb fractures following introduction of a simple guideline. METHODS: We developed and introduced a simple guideline for upper limb neurological assessment in children ('rock, paper, scissors, OK'). We compared documentation of neurological examination and nerve injury detection at our hospital before and after introduction of this guideline, as well as for children admitted from external hospitals (where the guideline had not been introduced). RESULTS: In the period following guideline introduction, 97 children with upper limb fractures were admitted (46% presenting directly to our ED and 54% admitted from external hospitals). This cohort was similar in number and distribution to the cohort reviewed prior to the guideline. Documentation of neurological examination in our ED increased from 92% to 98% after guideline introduction. Documented information on nerves examined also increased from 2% to 68% (p<0.01). Prior to the guideline, there were six nerve injuries, all of which were missed in our ED. After guideline introduction, there were four nerve injuries, all of which were detected in our ED. Documentation and nerve injury detection at external hospitals over the same time period showed no improvement. CONCLUSIONS: A simple guideline to assist neurological examination in children with upper limb fractures can significantly improve the quality of documented neurological assessment and nerve injury detection. PMID- 26880749 TI - Prioritizing quantitative trait loci for root system architecture in tetraploid wheat. AB - Optimization of root system architecture (RSA) traits is an important objective for modern wheat breeding. Linkage and association mapping for RSA in two recombinant inbred line populations and one association mapping panel of 183 elite durum wheat (Triticum turgidum L. var. durum Desf.) accessions evaluated as seedlings grown on filter paper/polycarbonate screening plates revealed 20 clusters of quantitative trait loci (QTLs) for root length and number, as well as 30 QTLs for root growth angle (RGA). Divergent RGA phenotypes observed by seminal root screening were validated by root phenotyping of field-grown adult plants. QTLs were mapped on a high-density tetraploid consensus map based on transcript associated Illumina 90K single nucleotide polymorphisms (SNPs) developed for bread and durum wheat, thus allowing for an accurate cross-referencing of RSA QTLs between durum and bread wheat. Among the main QTL clusters for root length and number highlighted in this study, 15 overlapped with QTLs for multiple RSA traits reported in bread wheat, while out of 30 QTLs for RGA, only six showed co location with previously reported QTLs in wheat. Based on their relative additive effects/significance, allelic distribution in the association mapping panel, and co-location with QTLs for grain weight and grain yield, the RSA QTLs have been prioritized in terms of breeding value. Three major QTL clusters for root length and number (RSA_QTL_cluster_5#, RSA_QTL_cluster_6#, and RSA_QTL_cluster_12#) and nine RGA QTL clusters (QRGA.ubo-2A.1, QRGA.ubo-2A.3, QRGA.ubo-2B.2/2B.3, QRGA.ubo 4B.4, QRGA.ubo-6A.1, QRGA.ubo-6A.2, QRGA.ubo-7A.1, QRGA.ubo-7A.2, and QRGA.ubo 7B) appear particularly valuable for further characterization towards a possible implementation of breeding applications in marker-assisted selection and/or cloning of the causal genes underlying the QTLs. PMID- 26880751 TI - Estrogen maintains myometrial tumors in a lymphangioleiomyomatosis model. AB - Lymphangioleiomyomatosis (LAM) is a rare disease in women. Patients with LAM develop metastatic smooth-muscle cell adenomas within the lungs, resulting in reduced pulmonary function. LAM cells contain mutations in tuberous sclerosis genes (TSC1 or TSC2), leading to up-regulation of mTORC1 activity and elevated proliferation. The origin of LAM cells remains unknown; however, inactivation of Tsc2 gene in the mouse uterus resulted in myometrial tumors exhibiting LAM features, and approximately 50% of animals developed metastatic myometrial lung tumors. This suggests that LAM tumors might originate from the uterine myometrium, possibly explaining the overwhelming prevalence of LAM in female. Here, we demonstrate that mouse Tsc2-null myometrial tumors exhibit nearly all the features of LAM, including mTORC1/S6K activation, as well as expression of melanocytic markers and matrix metalloproteinases (MMPs). Estrogen ablation reduces S6K signaling and results in Tsc2-null myometrial tumor regression. Thus, even without TSC2, estradiol is required to maintain tumors and mTORC1/S6K signaling. Additionally, we find that MMP-2 and -9, as well as neutrophil elastase (NE), are overexpressed in Tsc2-null myometrial tumors in an estrogen dependent fashion. In vivo fluorescent imaging using MMP- or NE-sensitive optical biomarkers confirms that protease activity is specific to myometrial tumors. Similar to LAM cells, uterine Tsc2-null myometrial cells also overexpress melanocytic markers in an estrogen-dependent fashion. Finally, we identify glycoprotein NMB (GPNMB) as a melanocytic marker up-regulated in Tsc2-null mouse uteri and human LAM samples. Our data highlight the potential importance of estradiol in LAM cells, suggesting that anti-estrogen therapy may be a treatment modality. Furthermore, proteases and GPNMB might be useful LAM biomarkers. PMID- 26880752 TI - Reverberation of excitation in neuronal networks interconnected through voltage gated gap junction channels. AB - We combined Hodgkin-Huxley equations and gating models of gap junction (GJ) channels to simulate the spread of excitation in two-dimensional networks composed of neurons interconnected by voltage-gated GJs. Each GJ channel contains two fast and slow gates, each exhibiting current-voltage (I-V) rectification and gating properties that depend on transjunctional voltage (Vj). The data obtained show how junctional conductance (gj), which is necessary for synchronization of the neuronal network, depends on its size and the intrinsic firing rate of neurons. A phase shift between action potentials (APs) of neighboring neurons creates bipolar, short-lasting Vj spikes of approximately +/- 100 mV that induce Vj gating, leading to a small decay of gj, which can accumulate into larger decays during bursting activity of neurons. We show that I-V rectification of GJs in local regions of the two-dimensional network of neurons can lead to unidirectional AP transfer and consequently to reverberation of excitation. This reverberation can be initiated by a single electrical pulse and terminated by a low-amplitude pulse applied in a specific window of reverberation cycle. Thus, the model accounts for the influence of dynamically modulatable electrical synapses in shaping the function of a neuronal network and the formation of reverberation, which, as proposed earlier, may be important for the development of short-term memory and its consolidation into long-term memory. PMID- 26880753 TI - Multiple cytosolic calcium buffers in posterior pituitary nerve terminals. AB - Cytosolic Ca(2+) buffers bind to a large fraction of Ca(2+) as it enters a cell, shaping Ca(2+) signals both spatially and temporally. In this way, cytosolic Ca(2+) buffers regulate excitation-secretion coupling and short-term plasticity of release. The posterior pituitary is composed of peptidergic nerve terminals, which release oxytocin and vasopressin in response to Ca(2+) entry. Secretion of these hormones exhibits a complex dependence on the frequency and pattern of electrical activity, and the role of cytosolic Ca(2+) buffers in controlling pituitary Ca(2+) signaling is poorly understood. Here, cytosolic Ca(2+) buffers were studied with two-photon imaging in patch-clamped nerve terminals of the rat posterior pituitary. Fluorescence of the Ca(2+) indicator fluo-8 revealed stepwise increases in free Ca(2+) after a series of brief depolarizing pulses in rapid succession. These Ca(2+) increments grew larger as free Ca(2+) rose to saturate the cytosolic buffers and reduce the availability of Ca(2+) binding sites. These titration data revealed two endogenous buffers. All nerve terminals contained a buffer with a Kd of 1.5-4.7 uM, and approximately half contained an additional higher-affinity buffer with a Kd of 340 nM. Western blots identified calretinin and calbindin D28K in the posterior pituitary, and their in vitro binding properties correspond well with our fluorometric analysis. The high affinity buffer washed out, but at a rate much slower than expected from diffusion; washout of the low-affinity buffer could not be detected. This work has revealed the functional impact of cytosolic Ca(2+) buffers in situ in nerve terminals at a new level of detail. The saturation of these cytosolic buffers will amplify Ca(2+) signals and may contribute to use-dependent facilitation of release. A difference in the buffer compositions of oxytocin and vasopressin nerve terminals could contribute to the differences in release plasticity of these two hormones. PMID- 26880755 TI - Correction: Orai1 pore residues control CRAC channel inactivation independently of calmodulin. PMID- 26880754 TI - Regulation of ENaC trafficking in rat kidney. AB - The epithelial Na channel (ENaC) forms a pathway for Na(+) reabsorption in the distal nephron, and regulation of these channels is essential for salt homeostasis. In the rat kidney, ENaC subunits reached the plasma membrane in both immature and fully processed forms, the latter defined by either endoglycosidase H-insensitive glycosylation or proteolytic cleavage. Animals adapted to a low salt diet have increased ENaC surface expression that is specific for the mature forms of the subunit proteins and is similar (three- to fourfold) for alpha, beta, and gammaENaC. Kidney membranes were fractionated using differential centrifugation, sucrose-gradient separation, and immunoabsorption. Endoplasmic reticulum membranes, isolated using an antibody against calnexin, expressed immature gammaENaC, and the content decreased with Na depletion. Golgi membranes, isolated with an antibody against the cis-Golgi protein GM130, expressed both immature and processed gammaENaC; Na depletion increased the content of processed gammaENaC in this fraction by 3.8-fold. An endosomal compartment isolated using an antibody against Rab11 contained both immature and processed gammaENaC; the content of processed subunit increased 2.4-fold with Na depletion. Finally, we assessed the content of gammaENaC in the late endocytic compartments indirectly using urinary exosomes. All of the gammaENaC in these exosomes was in the fully cleaved form, and its content increased by 4.5-fold with Na depletion. These results imply that stimulation of ENaC surface expression results at least in part from increased rates of formation of fully processed subunits in the Golgi and subsequent trafficking to the apical membrane. PMID- 26880757 TI - Autoethnography in Health Research: Growing Pains? AB - Autoethnography is gaining acceptance as a legitimate research method in health science research. The growing volume of published autoethnographies is indicative of this trend. After discussing the methodological tenents of this qualitative research method and its compatibility with health-related research, the author illustrates this trend with examples of published autoethnogrpahic books, theses, and journal articles. While celebrating the potential of autoethnography as a suitable health research method, the author critiques dominatly descriptive and evocative illness self-narratives that may evoke emontionally compelling responses from readers but offer insufficient sociocultural insights about the illness phenomenon. To identify a "desirable" autoethnography that provides not only a "thick description" of personal experiences but also a sociocultural interpration of such experiences, the author recommends both creators and consumers of autoethnography to ask five evaluative questions: (1) Does the autoethnography use authentic and trustworthy data?; (2) Does the autoethnography follow a reliable research process and show the process clearly?; (3) Does the autoethnography follow ethical steps to protect the rights of self and others presented and implicated in the autoethnography?; (4) Does the autoethnography analyze and interpret the sociocultural meaning of the author's personal experiences?; and (5) Does the autoethnography attempt to make a scholarly contribution with its conclusion and engagement of the existing literature? PMID- 26880758 TI - Does reactivity to accelerometers occur in a single trial? Brief report in a sample of young adults. AB - This study aimed to test acute reactivity during a physical activity in an outdoor setting and to verify the relative perceived performance. In all, 38 volunteers wore accelerometers or not and completed two 20-minute sessions of self-selected pace physical activity. Covered distance, exertional responses, and perceived efficacy were recorded at the end of every session. Relevant finding of this study has been that reactivity to accelerometers also occurs in acute condition. Consequently, this condition leads to a better performance and a greater perceived exertion. Moreover, this situation seems to occur in a state of awareness. PMID- 26880756 TI - Retigabine holds KV7 channels open and stabilizes the resting potential. AB - The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 and O2, with O2 being more stable. The O1 state was reached after short membrane depolarizations, whereas O2 was reached after prolonged depolarization or during steady state at the typical neuronal resting potentials. We also found that activation and deactivation seem to follow distinct pathways, suggesting that the KV7.2/KV7.3 channel activity displays hysteresis. As for the action of Retigabine, we discovered that this agonist discriminates between open states, preferentially acting on the O2 state and further stabilizing it. Based on these findings, we proposed a novel mechanism for the therapeutic effect of Retigabine whereby this drug reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. To address this hypothesis, we used a model for action potential (AP) in Xenopus laevis oocytes and found that the resting membrane potential became more negative as a function of Retigabine concentration, whereas the threshold potential for AP firing remained unaltered. PMID- 26880760 TI - Why people don't use family planning: how different methods of enquiry elicit different responses. AB - BACKGROUND: Engaging community, government and non-governmental organisation (NGO) stakeholders in the design of family planning (FP) programmes is best practice. Stakeholders can provide local insights on barriers to FP. However, it can be difficult to know whether there may be limited programme perceptions if only one method of enquiry is used. AIM: This study aimed to validate the perceptions of stakeholders on barriers to FP in Malawi. METHODS: The study was conducted in a rural area in Lilongwe District, Malawi and employed a mixed methods exploratory design. Five focus groups were run with community, government and NGO stakeholders to identify barriers to using modern FP. The results of the qualitative phase were then compared using a quantitative survey of 960 women who had at least one child aged under 5 years. RESULTS: The qualitative phase identified a range of barriers to FP, including lack of awareness, lack of access, religious beliefs, myths, and opposition by husbands. However, the quantitative survey found that these issues are not a concern for the majority of women. The main reasons given by women for not using FP were that were not currently having sex or had a child recently, and so they felt they did not need to use it. CONCLUSIONS: Perceptions of stakeholders from a qualitative approach do not necessarily reflect the perspectives of the population as documented in a quantitative survey. When involving stakeholders it is important to recognise that different approaches may elicit different responses, particularly with regard to sensitive issues or issues that apply to particular subgroups. Consequently, a deeper understanding is likely to be obtained by using a multimethod approach. PMID- 26880759 TI - Dual protection to address the global syndemic of HIV and unintended pregnancy in Brazil. AB - BACKGROUND: Syndemic HIV and unintended pregnancy is prevalent in Brazil, where 79% of female HIV cases occur in women of reproductive age and 55% of all pregnancies are unintended. Although increasing condom use to prevent HIV may decrease non-barrier contraception and increase unintended pregnancy, few studies focus on dual protection or dual methods (condoms with another modern contraceptive). AIM: To describe the correlates of dual method use and consistent condom use in women of reproductive age in Brazil. METHOD: Data are from the 2006 Pesquisa Nacional de Demografia e Saude da Mulher e da Crianca, a decennial nationally representative household survey of women of reproductive age in Brazil. Multivariate logistic regression models identify the socio-demographic, sexual debut, fertility and relationship factors associated with dual method use and consistent condom use. RESULTS: Two-thirds of contracepting women in Brazil used dual protection (40% exclusive condoms, 27% dual methods). Consistent condom use in the past year occurred among 61% of exclusive condom users and 27% of dual method users. Dual methods (vs exclusive condoms) was associated with some high school education [relative risk ratio (RRR)=1.69, p<0.05], living in the Southern region (RRR=1.59, p<0.01), and number of children (RRR=1.22, p<0.01), net of other factors. Consistent condom use was associated with condom use at sexual debut [adjusted odds ratio (AOR)=1.84, p<0.001], wants no (more) children (AOR=1.86, p<0.001), single/separated relationship status (AOR=2.77/2.45, p<0.001) and using exclusive condoms (vs dual methods: AOR=0.19, p<0.001). CONCLUSIONS: Findings highlight that targeting and delivering integrated HIV and family planning services should focus on completed/large families. single/separated individuals, and promoting dual protection at sexual debut. PMID- 26880761 TI - Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy. AB - Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL 6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface. PMID- 26880763 TI - In Vivo Visualizing the IFN-beta Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration. AB - The crucial role that endogenously produced IFN-beta plays in eliciting an immune response against cancer has recently started to be elucidated. Endogenous IFN beta has an important role in immune surveillance and control of tumor development. Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor. Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic explored empirically in cancer immunotherapy a long time ago with little knowledge regarding its mechanisms of action. In this work, we have in vivo visualized the IFN-beta required for the antitumor immune response elicited in a therapeutic model of poly A:U administration. In this study, we have identified the role of host type I IFNs, cell populations that are sources of IFN-beta in the tumor microenvironment, and other host requirements for tumor control in this model. One single peritumoral dose of poly A:U was sufficient to induce IFN-beta, readily visualized in vivo. IFN-beta production relied mainly on the activation of the transcription factor IFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 is required for recognizing poly A:U. CD11c(+) cells were an important, but not the only source of IFN-beta. Host type I IFN signaling was absolutely required for the reduced tumor growth, prolonged mice survival, and the strong antitumor-specific immune response elicited upon poly A:U administration. These findings add new perspectives to the use of IFN-beta inducing compounds in tumor therapy. PMID- 26880762 TI - LincRNA-Cox2 Promotes Late Inflammatory Gene Transcription in Macrophages through Modulating SWI/SNF-Mediated Chromatin Remodeling. AB - Long intergenic noncoding RNAs (lincRNAs) are long noncoding transcripts (>200 nt) from the intergenic regions of annotated protein-coding genes. One of the most highly induced lincRNAs in macrophages upon TLR ligation is lincRNA-Cox2, which was recently shown to mediate the activation and repression of distinct classes of immune genes in innate immune cells. We report that lincRNA-Cox2, located at chromosome 1 proximal to the PG-endoperoxide synthase 2 (Ptgs2/Cox2) gene, is an early-primary inflammatory gene controlled by NF-kappaB signaling in murine macrophages. Functionally, lincRNA-Cox2 is required for the transcription of NF-kappaB-regulated late-primary inflammatory response genes stimulated by bacterial LPS. Specifically, lincRNA-Cox2 is assembled into the switch/sucrose nonfermentable (SWI/SNF) complex in cells after LPS stimulation. This resulting lincRNA-Cox2/SWI/SNF complex can modulate the assembly of NF-kappaB subunits to the SWI/SNF complex, and ultimately, SWI/SNF-associated chromatin remodeling and transactivation of the late-primary inflammatory-response genes in macrophages in response to microbial challenge. Therefore, our data indicate a new regulatory role for NF-kappaB-induced lincRNA-Cox2 as a coactivator of NF-kappaB for the transcription of late-primary response genes in innate immune cells through modulation of epigenetic chromatin remodeling. PMID- 26880764 TI - A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis. AB - Frequently fatal, primary hemophagocytic lymphohistiocytosis (HLH) occurs in infancy resulting from homozygous mutations in NK and CD8 T cell cytolytic pathway genes. Secondary HLH presents after infancy and may be associated with heterozygous mutations in HLH genes. We report two unrelated teenagers with HLH and an identical heterozygous RAB27A mutation (c.259G->C). We explore the contribution of this Rab27A missense (p.A87P) mutation on NK cell cytolytic function by cloning it into a lentiviral expression vector prior to introduction into the human NK-92 cell line. NK cell degranulation (CD107a expression), target cell conjugation, and K562 target cell lysis was compared between mutant- and wild-type-transduced NK-92 cells. Polarization of granzyme B to the immunologic synapse and interaction of mutant Rab27A (p.A87P) with Munc13-4 were explored by confocal microscopy and proximity ligation assay, respectively. Overexpression of the RAB27A mutation had no effect on cell conjugate formation between the NK and target cells but decreased NK cell cytolytic activity and degranulation. Moreover, the mutant Rab27A protein decreased binding to Munc13-4 and delayed granzyme B polarization toward the immunologic synapse. This heterozygous RAB27A mutation blurs the genetic distinction between primary and secondary HLH by contributing to HLH via a partial dominant-negative effect. PMID- 26880766 TI - Expression and Regulation of Pituitary Adenylate Cyclase-Activating Polypeptide in Rat Placental Cells. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) was first identified as a hypophysiotropic factor that regulates pituitary cell functions and has been subsequently shown to be widely distributed and have multiple functions. The PACAP is known to be expressed in placental tissues and is suggested to have a critical role in physiological function of the placenta. In addition to PACAP, the hypothalamic peptides kisspeptin and gonadotropin-releasing hormone (GnRH) are also expressed in placental cells. In this study, we used primary cultures of placental tissues from rats of 16 to 18 days gestation and examined the regulation and function of PACAP. The PACAP messenger RNA (mRNA) expression and PACAP-immunoreactive cells were detected in primary cultures of rat placental cells. The PACAP mRNA expression in placental cells was upregulated in the presence of the sex steroids estradiol and progesterone; however, their combined treatment failed to enhance their individual effects. When the cells were stimulated with kisspeptin, PACAP mRNA expression was increased. Similarly, GnRH had a stimulatory effect on PACAP expression. Conversely, kisspeptin expression in placental cells was increased by PACAP stimulation, whereas PACAP failed to stimulate GnRH mRNA expression in these cells. Finally, we found that PACAP had a stimulatory effect on human chorionic gonadotropin expression in placental cells. Our current observations suggest that the hypothalamic peptides PACAP, kisspeptin, and GnRH are interrelated and maintain placental functions. PMID- 26880765 TI - T-bet Regulates Natural Regulatory T Cell Afferent Lymphatic Migration and Suppressive Function. AB - T-bet is essential for natural regulatory T cells (nTreg) to regulate Th1 inflammation, but whether T-bet controls other Treg functions after entering the inflammatory site is unknown. In an islet allograft model, T-bet(-/-) nTreg, but not induced Treg, failed to prolong graft survival as effectively as wild-type Treg. T-bet(-/-) nTreg had no functional deficiency in vitro but failed to home from the graft to draining lymph nodes (dLN) as efficiently as wild type. T-bet regulated expression of adhesion- and migration-related molecules, influencing nTreg distribution in tissues, so that T-bet(-/-) nTreg remained in the grafts rather than migrating to lymphatics and dLN. In contrast, both wild-type and T bet(-/-) CD4(+) conventional T cells and induced Treg migrated normally toward afferent lymphatics. T-bet(-/-) nTreg displayed instability in the graft, failing to suppress Ag-specific CD4(+) T cells and prevent their infiltration into the graft and dLN. Thus, T-bet regulates nTreg migration into afferent lymphatics and dLN and consequently their suppressive stability in vivo. PMID- 26880767 TI - Aberrant Methylation of the E-Cadherin Gene Promoter Region in the Endometrium of Women With Uterine Fibroids. AB - A uterine fibroid is a leiomyoma that originates from the smooth muscle layer of the uterus. A variety of endometrial abnormalities are associated with uterine fibroids. This study aims to investigate the methylation status of the E-cadherin gene (CDH1) promoter region in the endometrium of patients with uterine fibroids. The methylation of CDH1 was studied using methylation-specific polymerase chain reaction in the endometrial tissue of 102 patients with uterine fibroids and 50 control patients. The E-cadherin expression was examined by flow cytometry. The methylation rate of CDH1 promoter region was 33.3% in the endometrium of patients with uterine fibroids and 8% in the endometrium of women without fibroids. The frequency of CDH1 promoter methylation in the endometrium of patients with fibroids was significantly higher than that in the endometrium of women without fibroids (P = .001). Furthermore, the E-cadherin expression level in methylation positive tissues was significantly lower than that in methylation-negative tissues (P = .017). These results suggest that epigenetic aberration of CDH1 may occur in the endometrium of patients with fibroids, which may be associated with E-cadherin protein expression in endometrial tissue. PMID- 26880768 TI - Stresses on Female Mice Impair Oocyte Developmental Potential: Effects of Stress Severity and Duration on Oocytes at the Growing Follicle Stage. AB - AIM: Although previous studies found that 1-time acute stress applied during follicle maturation impaired oocyte competence, it is unknown whether repeated chronic stress, which is known to cause animal behavioral adaptation, would damage oocytes when applied during follicle growth. METHODS AND RESULTS: In this study, female mice were exposed to repeated restraint stress (RRS) or unpredictable stress (UPS) for different days before equine chorionic gonadotropin injection to initiate oocyte prematuration development and to observe effects of different stressors on oocytes in the growing follicles. The results showed that although oocyte pre- and postimplantation development was unaffected when mice were exposed to RRS or UPS once a day for 4 days, development was impaired when mice were exposed to RRS for 8 or more days or to UPS twice a day for 4 days (4 * 2). The 4 * 2 UPS caused more oxidative stress in oocytes and severer apoptosis in antral follicles than did the 4-day RRS. The RRS mice were stressed consistently from days 1 to 23 of restraint, and the stress that a mouse had 4 * 2 UPS was severer than that from 4-day RRS. CONCLUSION: The results suggest that (1) the degree that a stress damages oocytes is the product of duration * severity of the stress; (2) RRS impaired oocyte developmental potential through cumulative effects on growing follicles; and (3) preantral follicles were not as sensitive to stress as antral follicles were. PMID- 26880769 TI - Apelin in Normal Pregnancy and Pregnancies Complicated by Placental Insufficiency. AB - INTRODUCTION: Apelin is a potent inotropic agent and causes endothelium-mediated vasodilation. Its cardiovascular profile suggests a role in the regulation of gestational hemodynamics. METHODS: We longitudinally assessed maternal serum apelin levels and hemodynamics (cardiac output and total peripheral resistance) between 20 and 34 weeks gestation in 18 women at high risk of placental dysfunction. Placental apelin staining was assessed by immunohistochemistry in placentas from uncomplicated pregnancies (n = 6), preterm deliveries (n = 6), preeclampsia (PET, n = 8), and isolated intrauterine growth restriction (IUGR, n = 8). Placental apelin gene expression was assessed by quantitative polymerase chain reaction. RESULTS: In the high-risk cohort, 4 fetuses developed isolated IUGR and 6 women developed PET. We obtained a median of 5 (range 2-9) hemodynamic and apelin measurements per woman. Apelin levels throughout gestation were best fitted by a quadratic curve. Apelin levels between 20 and 26 weeks gestation correlated with total peripheral resistance (r = .57, P = .01) and showed a trend toward an inverse correlation with stroke volume (r = -.42, P = .08). Apelin serum levels were 30% lower in pregnancies complicated by IUGR than in uncomplicated pregnancies or in women with preeclampsia (P = .009). Placental apelin gene expression was similar in IUGR, PET, preterm, and term normal placentas. Apelin staining was seen both in syncytiotrophoblast and stroma of the placental villi. In IUGR placentas, apelin staining was strongly decreased in both compartments compared to normals. Preeclamptic placentas showed an intermediate staining. CONCLUSIONS: Apelin levels mirror the cardiovascular changes seen in pregnancy. Serum and placental apelin levels are decreased in IUGR. PMID- 26880771 TI - Controlling Malaria in Western Pacific with Mosquito Nets Treated with Pyrethroids in Village Communities, 1979-1999. AB - Insecticide-treated mosquito nets were first put to practical use in the Western Pacific Region. Less than a decade after conducting workshops and other promotional activities, millions of people were protected by 1989. This occurred before the availability of commercially produced pretreated nets and before global funding for mass net distribution. This paper describes the sequence of steps leading to regional control success. The beginning stages in 1979 recognized that treating torn mosquito nets was a viable control option. Basic net treatment procedures were established by 1983 and workshops were held the next 2 years in China, Cambodia, Laos, Malaysia, Papua New Guinea, Philippines, Solomon Islands, Vanuatu, and Vietnam. Malaria staff became convinced of net benefits and were motivated to impart their knowledge to others. Village inhabitants soaked the nets in washbasins containing permethrin or deltamethrin solution, then dried them horizontally on mats. By the 1990s, the population protected by nets had appreciably increased, and regional malaria cases confirmed by microscopy were markedly reduced. This coincided with commercial interest to mass-produce pretreated mosquito nets for worldwide use. PMID- 26880770 TI - The Presence and Seroprevalence of Arthropod-Borne Viruses in Nasiriyah Governorate, Southern Iraq: A Cross-Sectional Study. AB - The knowledge on the presence and seroprevalence of arboviruses in Iraq is fragmental. To assess the exposure of the population to arbovirus infections in southern Iraq, we conducted a serological screening of the most common arbovirus groups using immunofluorescence, hemagglutination inhibition and neutralization tests. Serum samples of 399 adult volunteers were collected in Nasiriyah, Iraq. Antibodies were detected against West Nile virus (WNV) (11.6%), sandfly-borne Sicilian virus serocomplex (18.2%), sandfly-borne Naples virus serocomplex (7.8%), Sindbis virus (1.5%), chikungunya virus (0.5%), and Tahyna virus (2.0%). The results suggest that WNV and sandfly-borne phlebovirus infections are common in southern Iraq, and these viruses should be considered as potential causative agents in patients with febrile disease and/or neurological manifestations. PMID- 26880772 TI - Extremely High Prevalence of Metronidazole-Resistant Helicobacter pylori Strains in Mountain People (Karen and Hmong) in Thailand. AB - This study aimed to survey the prevalence, patterns of antibiotic resistance, and clinical factors associated with antibiotic resistance in Helicobacter pylori among the Karen and Hmong mountain people of Thailand. We recruited dyspeptic patients in the Maesod district, Tak Province, Thailand. All subjects underwent upper gastrointestinal endoscopy, and three antral gastric biopsies were obtained for rapid urease tests and culture. An epsilometer was used to determine the minimum inhibitory concentrations of amoxicillin (AMX), clarithromycin (CLR), metronidazole (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET). A total of 291 subjects were enrolled; 149 (51.2%) were infected with H. pylori. Helicobacter pylori infection was present in 47.1% of Thai, 51.7% of Karen, and 58.7% of Hmong subjects. Antibiotic resistance was present in 75.8% including AMX (0.8%), TET (0%), CLR (5.6%), MNZ (71.8%), CIP (19.4%), LVX (19.4%), and multidrug resistance in 21.8%. Karen subjects had the highest prevalence of MNZ resistance (84.6%), and Hmong subjects had the highest prevalence of fluoroquinolone (27.3%) and multidrug (34.1%) resistance. MNZ plus fluoroquinolone (14.5%) was the most common multidrug resistance. There was no association between clinical factors and antibiotic resistance. MNZ resistance was prevalent, whereas fluoroquinolone- and multidrug-resistant H. pylori infections are important problems in mountain people of Thailand. PMID- 26880774 TI - Detection of Onchocerca volvulus in Skin Snips by Microscopy and Real-Time Polymerase Chain Reaction: Implications for Monitoring and Evaluation Activities. AB - Microscopic evaluation of skin biopsies is the monitoring and evaluation (M and E) method currently used by multiple onchocerciasis elimination programs in Africa. However, as repeated mass drug administration suppresses microfilarial loads, the sensitivity and programmatic utility of skin snip microscopy is expected to decrease. Using a pan-filarial real-time polymerase chain reaction with melt curve analysis (qPCR-MCA), we evaluated 1) the use of a single-step molecular assay for detecting and identifying Onchocerca volvulus microfilariae in residual skin snips and 2) the sensitivity of skin snip microscopy relative to qPCR-MCA. Skin snips were collected and examined with routine microscopy in hyperendemic regions of Uganda and Ethiopia (N= 500 each) and "residual" skin snips (tissue remaining after induced microfilarial emergence) were tested with qPCR-MCA. qPCR-MCA detected Onchocerca DNA in 223 residual snips: 139 of 147 microscopy(+) and 84 among microscopy(-) snips, suggesting overall sensitivity of microscopy was 62.3% (139/223) relative to qPCR-MCA (75.6% in Uganda and 28.6% in Ethiopia). These findings demonstrate the insufficient sensitivity of skin snip microscopy for reliable programmatic monitoring. Molecular tools such as qPCR-MCA can augment sensitivity and provide diagnostic confirmation of skin biopsies and will be useful for evaluation or validation of new onchocerciasis M and E tools. PMID- 26880773 TI - Quantifying Contact with the Environment: Behaviors of Young Children in Accra, Ghana. AB - To better understand the risks of exposure for young children to fecal contamination in their environment, we systematically characterized and quantified behaviors of 154 children, 0-5 years old, in four high-density, low income neighborhoods in Accra, Ghana. A repertoire of six different activities and five different compartments (categories of locations within the household) was developed, and about 500 hours of ordered structured observations of activities and locations of individual children were collected. These records were analyzed using a competing hazards model, estimating (Weibull) hazard rates for each state (activity/compartment combination), dependent on the present state and the preceding state. The estimated rates were used to simulate sequences of behavior and describe days in the life of a child in low-income, urban Africa. Children younger than 1 year spent most time playing or sleeping off the ground, older children frequently played on floors. Relatively little time was spent in drains or wet trash areas. Critical combinations of activities, like handwashing after defecation or before eating were estimated to occur rarely. These quantitative behavior estimates can inform future risk assessments that examine the relative roles of various fecal-oral exposure pathways in low-income urban settings. PMID- 26880775 TI - The Utility of Blood Culture Fluid for the Molecular Diagnosis of Leptospira: A Prospective Evaluation. AB - Leptospirosis is an important zoonosis worldwide, with infections occurring after exposure to contaminated water. Despite being a global problem, laboratory diagnosis remains difficult with culture results taking up to 3 months, serology being retrospective by nature, and polymerase chain reaction showing limited sensitivity. Leptospira have been shown to survive and multiply in blood culture media, and we hypothesized that extracting DNA from incubated blood culture fluid (BCF), followed by quantitative real-time polymerase chain reaction (qPCR) could improve the accuracy and speed of leptospira diagnosis. We assessed this retrospectively, using preincubated BCF of Leptospira spp. positive (N= 109) and negative (N= 63) febrile patients in Vientiane, Lao PDR. The final method showed promising sensitivities of 66% (95% confidence interval [CI]: 55-76) and 59% (95% CI: 49-68) compared with direct or direct and indirect testing combined, as the respective reference standards (specificities > 95%). Despite these promising diagnostic parameters, a subsequent prospective evaluation in a Lao hospital population (N= 352) showed that the sensitivity was very low (~30%) compared with qPCR on venous blood samples. The disappointingly low sensitivity does suggest that venous blood samples are preferable for the clinical microbiology laboratory, although BCF might be an alternative if leptospirosis is only suspected postadmission after antibiotics have been used. PMID- 26880776 TI - Polyandry Depends on Postmating Time Interval in the Dengue Vector Aedes aegypti. AB - Aedes aegypti is the primary vector of the dengue and chikungunya viruses. After mating, male seminal fluid molecules cause females to become unreceptive to a subsequent mating. This response is often assumed to be immediate and complete, but a growing body of evidence suggests that some females do mate more than once. It is unknown how quickly a female becomes unreceptive to a second mating. Furthermore, the degree to which she remains monandrous after laying several batches of eggs has not been rigorously tested. Therefore, we assessed the rates of polyandry in two sets of experiments using wild-type males and those with fluorescent sperm. The first experiment tested the likelihood of polyandry after postmating intervals of various durations. Most females became refractory to a second mating within 2 hours after mating, and rates of polyandry ranged from 24% immediately after mating to 3% at 20 hours after mating. The second experiment tested whether females were polyandrous after cycles of blood meals and oviposition. No re-insemination was found after one, three, or five such cycles. This study is the first to demonstrate that polyandrous behavior depends on the postmating interval. Our results will inform future applications that depend on an accurate knowledge of Ae. aegypti mating behavior, including models of gene flow, investigations of molecules that drive female mating behavior, and control strategies that deploy genetically modified mosquitoes into the field. PMID- 26880777 TI - An Emerging Epidemic of Noncommunicable Diseases in Developing Populations Due to a Triple Evolutionary Mismatch. AB - With their transition from adverse to affluent environments, developing populations experience a rapid increase in the number of individuals with noncommunicable diseases. Here, we emphasize that developing populations are more susceptible than western populations to acquire these chronic diseases, because their genetic, cultural, and epigenetic characteristics do not match with the eagerly awaited affluent environments. In regard to this, there is an urgent need for public health organizations to reorganize current environments in developing populations so as to fit their inherited characteristics. Unfortunately, this need is neglected as an essential part of the Sustainable Development Goals that form the core of the United Nations' Post-2015 Development Agenda. Only through global collaborative efforts can the environments in developing populations be reorganized and, thereby, the emerging epidemic of noncommunicable diseases be stalled. PMID- 26880778 TI - Assessing the Contribution of Malaria Vector Control and Other Maternal and Child Health Interventions in Reducing All-Cause Under-Five Mortality in Zambia, 1990 2010. AB - Under-five mortality in Zambia has declined since 1990, with reductions accelerating after 2000. Zambia's scale-up of malaria control is viewed as the driver of these gains, but past studies have not fully accounted for other potential factors. This study sought to systematically evaluate the impact of malaria vector control on under-five mortality. Using a mixed-effects regression model, we quantified the relationship between malaria vector control, other priority health interventions, and socioeconomic indicators and district-level under-five mortality trends from 1990 to 2010. We then conducted counterfactual analyses to estimate under-five mortality in the absence of scaling up malaria vector control. Throughout Zambia, increased malaria vector control coverage coincided with scaling up three other interventions: the pentavalent vaccine, exclusive breast-feeding, and prevention of mother-to-child transmission of HIV services. This simultaneous scale-up made statistically isolating intervention specific impact infeasible. Instead, in combination, these interventions jointly accelerated declines in under-five mortality by 11% between 2000 and 2010. Zambia's scale-up of multiple interventions is notable, yet our findings highlight challenges in quantifying program-specific impact without better health data and information systems. As countries aim to further improve health outcomes, there is even greater need-and opportunity-to strengthen routine data systems and to develop more rigorous evaluation strategies. PMID- 26880779 TI - Laboratory-Based Surveillance and Molecular Characterization of Dengue Viruses in Taiwan, 2014. AB - We present the results of a laboratory-based surveillance of dengue in Taiwan in 2014. A total of 240 imported dengue cases were identified. The patients had arrived from 16 countries, and Malaysia, Indonesia, the Philippines, and China were the most frequent importing countries. Phylogenetic analyses showed that genotype I of dengue virus type 1 (DENV-1) and the cosmopolitan genotype of DENV 2 were the predominant DENV strains circulating in southeast Asia. The 2014 dengue epidemic was the largest ever to occur in Taiwan since World War II, and there were 15,492 laboratory-confirmed indigenous dengue cases. Phylogenetic analysis showed that the explosive dengue epidemic in southern Taiwan was caused by a DENV-1 strain of genotype I imported from Indonesia. There were several possible causes of this outbreak, including delayed notification of the outbreak, limited staff and resources for control measures, abnormal weather conditions, and a serious gas pipeline explosion in the dengue hot spot areas in Kaohsiung City. However, the results of this surveillance indicated that both active and passive surveillance systems should be strengthened so appropriate public health measures can be taken promptly to prevent large-scale dengue outbreaks. PMID- 26880780 TI - Cost and Predictors of Care-Seeking Behaviors Among Caregivers of Febrile Children-Uganda, 2009. AB - Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs--both financial and nonfinancial--remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary. PMID- 26880781 TI - Real-Time Polymerase Chain Reaction in Stool Detects Transmission of Strongyloides stercoralis from an Infected Donor to Solid Organ Transplant Recipients. AB - Solid organ transplant recipients can acquire Strongyloides stercoralis from an infected donor. The diagnosis of S. stercoralis in immunocompromised individuals may be challenging due to a lower sensitivity of available parasitological and serological methods, compared with immunocompetent individuals. Recently, a real time polymerase chain reaction (RT-PCR) in stool has been developed for S. stercoralis diagnosis. We report two cases of S. stercoralis infection transmitted by a donor to two solid organ transplant recipients, who were diagnosed with RT-PCR in stool. This test could play an important role inS. stercoralis diagnosis in immunosuppressed patients, facilitating rapid treatment initiation and reducing the risk of severe strongyloidiasis. Adherence to current recommendations of screening among donors and recipients from endemic areas is also urgently needed. PMID- 26880782 TI - Infectious Diseases in Sub-Saharan Immigrants to Spain. AB - Immigrants may be carriers of infectious diseases because of the prevalence of these diseases in their country of origin, exposure during migration, or conditions during resettlement, with this prevalence being particularly high in sub-Saharan Africans. We performed a retrospective review of 180 sub-Saharan immigrants screened for infectious diseases at an International Health Center from January 2009 to December 2012. At least one pathogenic infectious disease was diagnosed in 72.8% patients: 60.6% latent tuberculosis infection, 36.8% intestinal parasites (intestinal protozoa or helminths), 28.1% helminths, 14.8% hepatitis B surface antigen positive, 1.2% anti-hepatitis C virus positive, 1.2% human immunodeficiency virus-positive, and 1.2% malaria. Coinfections were present in 28.4%. There was significant association between eosinophilia (absolute count or percentage) or hyper-IgE and the presence of helminths (P< 0.001). Relative eosinophilia and hyper-IgE were better indicators of helminth infection than absolute eosinophilia, particularly for schistosomiasis and strongyloidiasis. We found a high prevalence of infectious diseases in sub Saharan immigrants, which could lead to severe health problems (in the absence of prompt treatment), representing a high cost to the public health system and possible transmission in the host country. Accurate screening and tailored protocols for infectious diseases are recommended in sub-Saharan immigrants. PMID- 26880783 TI - Changes of soil prokaryotic communities after clear-cutting in a karst forest: evidences for cutting-based disturbance promoting deterministic processes. AB - To understand the temporal responses of soil prokaryotic communities to clear cutting disturbance, we examined the changes in soil bacterial and archaeal community composition, structure and diversity along a chronosequence of forest successional restoration using high-throughput 16S rRNA gene sequencing. Our results demonstrated that clear-cutting significantly altered soil bacterial community structure, while no significant shifts of soil archaeal communities were observed. The hypothesis that soil bacterial communities would become similar to those of surrounding intact primary forest with natural regeneration was supported by the shifts in the bacterial community composition and structure. Bacterial community diversity patterns induced by clear-cutting were consistent with the intermediate disturbance hypothesis. Dynamics of bacterial communities was mostly driven by soil properties, which collectively explained more than 70% of the variation in bacterial community composition. Community assembly data revealed that clear-cutting promoted the importance of the deterministic processes in shaping bacterial communities, coinciding with the resultant low resource environments. But assembly processes in the secondary forest returned a similar level compared to the intact primary forest. These findings suggest that bacterial community dynamics may be predictable during the natural recovery process. PMID- 26880784 TI - Diversity of the nitrogen starvation responses in subarctic Desmodesmus sp. (Chlorophyceae) strains isolated from symbioses with invertebrates. AB - We report on common and strain-specific responses to nitrogen (N) starvation recorded in four closely related symbiotic Desmodesmus strains from taxonomically very distant animals (hydroids, a sponge and a polychaete) dwelling in the White Sea. A number of common for the studied strains and free-living microalgae as well as some specific patterns of acclimation to the N starvation were documented. The common responses included a slowdown of cell division, a reduction of photosynthetic apparatus and a vast expansion of storage subcompartments of the cell. Although these responses were qualitatively similar to those known in free-living chlorophytes, in the studied strains they occurred in a strain-specific manner. The specific N-starvation responses comprised formation of chloroplast envelope membrane twirls, thinning of the appressed thylakoid membranes and a loss of the luminal depositions and channeling of the fixed carbon to cell wall polysaccharide layer. Desmodesmus sp. from a hydroid featured a unique, among the studied strains, capability of 'emergency' degradation of Rubisco, apparently to salvage the N contained in this protein. The obtained results are discussed in view of the remarkable physiological plasticity of the symbiotic Desmodesmus spp. and their survival under the harsh conditions of the subarctic sea habitat. PMID- 26880785 TI - Characterization of the faecal bacterial community of wild young South American (Arctocephalus australis) and Subantarctic fur seals (Arctocephalus tropicalis). AB - The microbiota of wild marine mammals is poorly understood, perhaps due to the migratory habits of some species and the difficulty in obtaining samples. Using high-throughput sequencing, the present study examines the faecal bacterial community of wild young South American (Arctocephalus australis) and Subantarctic fur seals (A. tropicalis). Faecal samples from South American (n = 6) and Subantarctic fur seals (n = 4) found dead along the south coast of Brazil were collected. Sequences were assigned to taxa using the Ribosomal Database Project Bayesian classifier. Diversity of the microbiota was assessed by categorization of sequence reads into operational taxonomic units. Results indicate that Firmicutes (88.556%-84.016%) was the predominant phylum in South American and Subantarctic fur seals. The distribution of Actinobacteria and Proteobacteria varied according to the fur seal species. Fusobacteria and Bacteroidetes represented less than 1% of the sequences. The most abundant order in both fur seals was Clostridiales (88.64% and 87.49%). Individual variable incidences were observed in the composition of family among the fur seals, though the families Lachnospiraceae, Peptostreptococcaceae, Ruminococcaceae and Coriobacteriaceae were more prevalent. This study provides insight into the faecal bacterial community of wild young South American and Subantarctic fur seals. PMID- 26880787 TI - Antimicrobial prescribing practices by Swiss, German and Austrian equine practitioners. PMID- 26880788 TI - Preventative Services for Sexual Offenders. AB - The role of primary prevention of sexual offences is an understudied area. The current study examined a sample ( N = 100) of men charged or convicted of a sexual offence to determine their interest in interventions that could be offered prior to offending, reasons for not seeking out interventions in the past, and demographic information including onset of deviant sexual fantasy and interests. The majority indicated that preventative interventions, including individual and group treatment, would have been beneficial, but inaccessibility of interventions and fear of arrest prevented them from seeking services. The findings suggest that men who progress to committing a sexual offence are interested in preventative interventions but require information regarding availability of accessible support and the development of primary prevention structures to fulfill society's desire to prevent sexual offending. PMID- 26880786 TI - Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2-/ ) or obese (ob/ob) mice. AB - Reducing triacylglycerol (TAG) in the liver continues to pose a challenge in states of nonalcoholic hepatic steatosis. MonoacylglycerolO-acyltransferase (MOGAT) enzymes convert monoacylglycerol (MAG) to diacylglycerol, a precursor for TAG synthesis, and are involved in a major pathway of TAG synthesis in selected tissues, such as small intestine. MOGAT1 possesses MGAT activity in in vitro assays, but its physiological function in TAG metabolism is unknown. Recent studies suggest a role for MOGAT1 in hepatic steatosis in lipodystrophic [1 acylglycerol-3-phosphateO-acyltransferase (Agpat)2(-/-)] and obese (ob/ob) mice. To test this, we deletedMogat1in theAgpat2(-/-)andob/obgenetic background to generateMogat1(-/-);Agpat2(-/-)andMogat1(-/-);ob/obdouble knockout (DKO) mice. Here we report that, despite the absence ofMogat1in either DKO mouse model, we did not find any decrease in liver TAG by 16 weeks of age. Additionally, there were no measureable changes in plasma glucose (diabetes) and insulin resistance. Our data indicate a minimal role, if any, of MOGAT1 in liver TAG synthesis, and that TAG synthesis in steatosis associated with lipodystrophy and obesity is independent of MOGAT1. Our findings suggest that MOGAT1 likely has an alternative function in vivo. PMID- 26880789 TI - Exploring Neural Correlates of Empathy in Juveniles Who Have Sexually Offended. AB - To effectively address the needs of youth who perpetrate sexual violence and reduce rates of recidivism, a better understanding of the mechanisms of juvenile sexual offending is needed. Current literature identifies various factors that are believed to put youth at risk for sexual offending, two of which are empathy deficits and childhood sexual abuse (CSA). The extent to which empathy deficits contribute to juvenile sexual offending, however, is often debated, though studies have not yet explored a neurobehavioral model of this mechanism. This pilot study used functional magnetic resonance imaging (fMRI) to explore the neural correlates of empathy in juveniles who sexually offend (JSOs), and the possible role of CSA. A total of 38 males (ages 12-20) were enrolled, including 11 healthy control subjects and 27 JSOs, of which, 11 had a history of CSA. Participants underwent clinical assessment and completed an empathy task during fMRI. Using both whole-brain and region-of-interest analysis, results of the fMRI data showed no statistical differences in engagement of brain regions associated with empathy between controls and all JSOs. There were also no significant differences between JSOs with and without a history of CSA. These null findings pose implications for guiding future research studies with larger samples and more statistical power, and may support the need to further explore empathy related explanatory models and interventions for JSOs. Neuroimaging may demonstrate to be a useful tool to identify individualized risk factors and aid in tailoring interventions for this population. PMID- 26880790 TI - Risk factors for preoperative respiratory complications in children with tracheobronchial foreign bodies. AB - OBJECTIVE: To identify risk factors for preoperative respiratory complications associated with tracheobronchial foreign body aspiration (TFBA) by retrospectively analysing paediatric cases presenting with or without complications. METHODS: Paediatric patients who presented with TFBA and were admitted to hospital were enrolled in the study. Patients were divided into two groups based on occurrence of preoperative respiratory complications as confirmed by computed tomography. Age, sex, TFBA symptoms, type of foreign body, retention timeand location of the foreign body were documented and compared between the groups. RESULTS: In total, 223 children were included: group A (n = 161) included those with respiratory complications; group B (n = 62) included those without respiratory complications. Univariate and multivariate analyses found that type of foreign body, and symptoms differed significantly between the two groups. CONCLUSION: Respiratory complications of TFBA in children were correlated with the type of foreign body and symptoms. PMID- 26880791 TI - Plate fixation versus intramedullary fixation for midshaft clavicle fractures: Meta-analysis of complications and functional outcomes. AB - OBJECTIVE: This analysis critically compares publications discussing complications and functional outcomes of plate fixation (PF) versus intramedullary fixation (IF) for midshaft clavicle fractures. METHODS: Relevant studies published between January 1990 and October 2014, without language restrictions, were identified in database searches of PubMed(r), Medline(r), Embase and the Chinese National Knowledge Infrastructure (CNKI). Studies that compared postoperative complications and functional outcomes between PF and IF for midshaft clavicle fractures, and provided sufficient data for analysis, were included in this meta-analysis. RESULTS: After strict evaluation, 12 studies were included in this meta-analysis. Studies encompassed 462 participants in the PF group and 440 in the IF group. Study participants were followed up for >=1 year. Outcomes were superior with IF compared with PF in terms of shoulder constant score at 6-month follow-up, fewer symptomatic hardware complications, lower rate of refracture after hardware removal and less hypertrophic scarring. In other aspects, such as functional recovery at 12-months and 24-months, Disability of Arm, Shoulder and Hand (DASH) questionnaire results at 12-month follow-up, shoulder motion range, rates of superficial infection, temporary brachial plexus lesion, nonunion, malunion, delayed union, implant failure and need for major revision, both techniques were similar. CONCLUSIONS: Findings of this meta analysis suggest that, in many respects, IF was superior to PF for the management of midshaft clavicle fractures. This finding could aid surgeons in making decisions on the optimum internal fixation pattern for midshaft clavicular fractures. PMID- 26880792 TI - Epidermal growth factor and prostaglandin E2 levels in Helicobacter pylori positive gastric intraepithelial neoplasia. AB - OBJECTIVE: To investigate levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2) in Han Chinese patients with Helicobacter pylori-positive gastric low-grade intraepithelial neoplasia (LGIN). METHODS: In this prospective, observational study, gastric specimens from patients with LGIN were collected by gastroscopy with consecutive biopsy. EGF and PGE2 concentrations in serum and gastric juice from patients with LGIN were measured by enzyme-linked immunosorbent assay. Presence of H. pylori infection was assessed in patients with LGIN and healthy controls. RESULTS: Out of 5 638 patients and 548 controls, H. pylori infection in patients with chronic gastritis was associated with disease type (endoscopic classification) and disease severity. Patients with H. pylori-positive LGIN had significantly higher concentrations of serum EGF and lower concentrations of serum PGE2 versus patients with H. pylori-negative LGIN. Serum EGF and PGE2 levels in patients with LGIN were not significantly associated with disease type, but were significantly associated with disease severity. CONCLUSIONS: H. pylori infection was associated with chronic gastritis type (endoscopic classification) and disease severity. Abnormal EGF and PGE2 levels may be associated with H. pylori-positive LGIN in Han Chinese patients in central China. PMID- 26880793 TI - Early stage primary ovarian mucinous carcinoma: Outcome-based clinicopathological study in comparison with serous carcinoma. AB - OBJECTIVE: To compare clinicopathological characteristics and survival rates between patients with primary ovarian mucinous carcinoma and those with primary ovarian serous carcinoma. METHODS: This retrospective study reviewed archival tumour specimens, originally diagnosed as primary ovarian mucinous carcinoma, using refined histological criteria. All patients were contacted to establish survival status. Clinicopathological characteristics and patient survival data were compared with a group of control patients with primary ovarian serous carcinoma. RESULTS: Of the 33 patients originally diagnosed with primary ovarian mucinous carcinoma, this diagnosis was only confirmed in 18. Primary ovarian mucinous carcinoma was more commonly associated with early International Federation of Gynecology and Obstetrics tumour stages and low-grade histology than primary ovarian serous carcinoma. Patients with primary ovarian mucinous carcinoma had a significantly higher overall 5-year survival rate than those with primary ovarian serous carcinoma (12/12 [100%] versus 14/24 [58%]). Kaplan-Meier survival plots demonstrated that patients with primary ovarian mucinous carcinoma had a survival advantage over patients with primary ovarian serous carcinoma. CONCLUSIONS: Primary ovarian mucinous carcinomas are frequently low-grade, stage I tumours and have an excellent prognosis. PMID- 26880794 TI - Comparison of effects of intravenous midazolam and ketamine on emergence agitation in children: Randomized controlled trial. AB - OBJECTIVE: A prospective, double-blind, randomized controlled trial to compare the effect of preoperative midazolam or ketamine on the incidence of emergence agitation (EA) following sevoflurane anaesthesia in children. METHODS: Paediatric patients (2-6 years old) undergoing ophthalmic surgery were allocated to receive premedication with either 0.1 mg/kg midazolam or 1 mg/kg ketamine. Incidence of EA and postoperative pain scores were recorded at 10-min intervals in the postanaesthetic care unit (PACU). The use of EA rescue medications (fentanyl or midazolam) was recorded. RESULTS: The incidence of EA was significantly lower in the ketamine group (n = 33) than the midazolam group (n = 34) at 10 and 20 min after transfer to PACU. There was no significant difference in overall incidence of EA. The frequency of midazolam use as rescue medication was significantly lower in the katamine group than in the midazolam group. CONCLUSION: Premedication with ketamine is more effective than midazolam in preventing EA during the early emergence period after sevoflurane anaesthesia in children. PMID- 26880795 TI - MiR-205 promotes proliferation, migration and invasion of nasopharyngeal carcinoma cells by activation of AKT signalling. AB - OBJECTIVE: To examine the role of microRNA (miR)-205 in proliferation, migration and invasion of nasopharyngeal carcinoma (NPC). METHODS: The human NPC cell line CNE2 was transfected with miR-205 mimic, anti-miR-205 inhibitor or scrambled oligonucleotide (control). Cell proliferation was assessed via MTT assay. Cell migration and invasion were evaluated by transwell migration and Matrigel(r) invasion assay, respectively. Radiation induced apoptosis was quantified via Caspase-Glo3/7 assay. Apoptotic proteins and epithelial-mesenchymal transition (EMT) proteins were semiquantified by Western blot analysis. RESULTS: Overexpression of miR-205 increased the proliferation, migration and invasion of CNE2 cells, and decreased radiation-induced apoptosis compared with control cells. MiR-205 overexpression downregulated E-cadherin and upregulated Snail expression via downregulation of PTEN and upregulation of AKT. CONCLUSION: MiR 205 plays vital roles in tumourigenesis and tumour progression in NPC, and may be a potential treatment target. PMID- 26880797 TI - Asynchronous spore germination in isogenic natural isolates of Saccharomyces paradoxus. AB - Spores from wild yeast isolates often show great variation in the size of colonies they produce, for largely unknown reasons. Here we measure the colonies produced from single spores from six different wild Saccharomyces paradoxus strains. We found remarkable variation in spore colony sizes, even among spores that were genetically identical. Different strains had different amounts of variation in spore colony sizes, and variation was not affected by the number of preceding meioses, or by spore maturation time. We used time-lapse photography to show that wild strains also have high variation in spore germination timing, providing a likely mechanism for the variation in spore colony sizes. When some spores from a laboratory strain make small colonies, or no colonies, it usually indicates a genetic or meiotic fault. Here, we demonstrate that in wild strains spore colony size variation is normal. We discuss and assess potential adaptive and non-adaptive explanations for this variation. PMID- 26880798 TI - (-)-Nortrachelogenin from Partrinia scabiosaefolia elicits an apoptotic response in Candida albicans. AB - This study analyzes the antifungal properties of (-)-nortrachelogenin and elucidates its mode of action against pathogenic fungi. We performed susceptibility tests against several pathogenic fungi and verified the absence of hemolysis against human erythrocytes. Its antifungal activity increased reactive oxygen species (ROS) in response to intracellular stress and increased concentrations of both intracellular and extracellular trehalose without causing hemolysis. In addition, a cell wall regeneration study indicated its action on the cytoplasmic membrane. A cell surface study using 3,3(') dipropylthiacarbocyanine iodide [DiSC3(5)] and 1,6-diphenyl-1,3,5-hexatriene (DPH) demonstrated dissipation of the cytoplasmic membrane at high concentrations. Our study revealed a disturbance in the membrane at higher concentrations and externalization of phosphatidylserine in a dose-dependent manner, affecting other intracellular responses. Furthermore, we investigated the late stage of apoptosis using TUNEL and 4('),6-diamidino-2-phenylindole (DAPI) assays. (-)-Nortrachelogenin-treated cells underwent apoptosis which was triggered by mitochondrial dysfunction via depolarization of the mitochondrial membrane, release of cytochrome c and calcium ion signaling, resulting in the activation of metacaspases. Different concentrations of (-)-nortrachelogenin induced membrane disruption and caspase-dependent apoptosis. PMID- 26880796 TI - 60 YEARS OF POMC: Biosynthesis, trafficking, and secretion of pro opiomelanocortin-derived peptides. AB - Pro-opiomelanocortin (POMC) is a prohormone that encodes multiple smaller peptide hormones within its structure. These peptide hormones can be generated by cleavage of POMC at basic residue cleavage sites by prohormone-converting enzymes in the regulated secretory pathway (RSP) of POMC-synthesizing endocrine cells and neurons. The peptides are stored inside the cells in dense-core secretory granules until released in a stimulus-dependent manner. The complexity of the regulation of the biosynthesis, trafficking, and secretion of POMC and its peptides reflects an impressive level of control over many factors involved in the ultimate role of POMC-expressing cells, that is, to produce a range of different biologically active peptide hormones ready for action when signaled by the body. From the discovery of POMC as the precursor to adrenocorticotropic hormone (ACTH) and beta-lipotropin in the late 1970s to our current knowledge, the understanding of POMC physiology remains a monumental body of work that has provided insight into many aspects of molecular endocrinology. In this article, we describe the intracellular trafficking of POMC in endocrine cells, its sorting into dense-core secretory granules and transport of these granules to the RSP. Additionally, we review the enzymes involved in the maturation of POMC to its various peptides and the mechanisms involved in the differential processing of POMC in different cell types. Finally, we highlight studies pertaining to the regulation of ACTH secretion in the anterior and intermediate pituitary and POMC neurons of the hypothalamus. PMID- 26880799 TI - Serum Glucocorticoid-Regulated Kinase 1 Blocks CKD-Induced Muscle Wasting Via Inactivation of FoxO3a and Smad2/3. AB - Muscle proteolysis in CKD is stimulated when the ubiquitin-proteasome system is activated. Serum glucocorticoid-regulated kinase 1 (SGK-1) is involved in skeletal muscle homeostasis, but the role of this protein in CKD-induced muscle wasting is unknown. We found that, compared with muscles from healthy controls, muscles from patients and mice with CKD express low levels of SGK-1. In mice, SGK 1-knockout (SGK-1-KO) induced muscle loss that correlated with increased expression of ubiquitin E3 ligases known to facilitate protein degradation by the ubiquitin-proteasome, and CKD substantially aggravated this response. SGK-1-KO also altered the phosphorylation levels of transcription factors FoxO3a and Smad2/3. In C2C12 muscle cells, expression of dominant negative FoxO3a or knockdown of Smad2/3 suppressed the upregulation of E3 ligases induced by loss of SGK-1. Additionally, SGK-1 overexpression increased the level of phosphorylated N myc downstream-regulated gene 1 protein, which directly interacted with and suppressed the phosphorylation of Smad2/3. Overexpression of SGK-1 in wild-type mice with CKD had similar effects on the phosphorylation of FoxO3a and Smad2/3 and prevented CKD-induced muscle atrophy. Finally, mechanical stretch of C2C12 muscle cells or treadmill running of wild-type mice with CKD stimulated SGK-1 production, and treadmill running inhibited proteolysis in muscle. These protective responses were absent in SGK-1-KO mice. Thus, SGK-1 could be a mechanical sensor that mediates exercise-induced improvement in muscle wasting stimulated by CKD. PMID- 26880801 TI - Small-Molecule Inhibition of GCNT3 Disrupts Mucin Biosynthesis and Malignant Cellular Behaviors in Pancreatic Cancer. AB - Pancreatic cancer is an aggressive neoplasm with almost uniform lethality and a 5 year survival rate of 7%. Several overexpressed mucins that impede drug delivery to pancreatic tumors have been therapeutically targeted, but enzymes involved in mucin biosynthesis have yet to be preclinically evaluated as potential targets. We used survival data from human patients with pancreatic cancer, next-generation sequencing of genetically engineered Kras-driven mouse pancreatic tumors and human pancreatic cancer cells to identify the novel core mucin-synthesizing enzyme GCNT3 (core 2 beta-1,6 N-acetylglucosaminyltransferase). In mouse pancreatic cancer tumors, GCNT3 upregulation (103-fold; P < 0.0001) was correlated with increased expression of mucins (5 to 87-fold; P < 0.04-0.0003). Aberrant GCNT3 expression was also associated with increased mucin production, aggressive tumorigenesis, and reduced patient survival, and CRISPR-mediated knockout of GCNT3 in pancreatic cancer cells reduced proliferation and spheroid formation. Using in silico small molecular docking simulation approaches, we identified talniflumate as a novel inhibitor that selectively binds to GCNT3. In particular, docking predictions suggested that three notable hydrogen bonds between talniflumate and GCNT3 contribute to a docking affinity of -8.3 kcal/mol. Furthermore, talniflumate alone and in combination with low-dose gefitinib reduced GCNT3 expression, leading to the disrupted production of mucins in vivo and in vitro Collectively, our findings suggest that targeting mucin biosynthesis through GCNT3 may improve drug responsiveness, warranting further development and investigation in preclinical models of pancreatic tumorigenesis. Cancer Res; 76(7); 1965-74. (c)2016 AACR. PMID- 26880800 TI - Myeloid-Derived Suppressor Cells Express Bruton's Tyrosine Kinase and Can Be Depleted in Tumor-Bearing Hosts by Ibrutinib Treatment. AB - Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that expand in tumor-bearing hosts in response to soluble factors produced by tumor and stromal cells. MDSC expansion has been linked to loss of immune effector cell function and reduced efficacy of immune-based cancer therapies, highlighting the MDSC population as an attractive therapeutic target. Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and IL2 inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies. Here, we report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells. Treatment of MDSCs with ibrutinib significantly impaired nitric oxide production and cell migration. In addition, ibrutinib inhibited in vitro generation of human MDSCs and reduced mRNA expression of indolamine 2,3-dioxygenase, an immunosuppressive factor. Treatment of mice bearing EMT6 mammary tumors with ibrutinib resulted in reduced frequency of MDSCs in both the spleen and tumor. Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model. Together, these results demonstrate that ibrutinib modulates MDSC function and generation, revealing a potential strategy for enhancing immune based therapies in solid malignancies. Cancer Res; 76(8); 2125-36. (c)2016 AACR. PMID- 26880802 TI - Redundant Innate and Adaptive Sources of IL17 Production Drive Colon Tumorigenesis. AB - IL17-producing Th17 cells, generated through a STAT3-dependent mechanism, have been shown to promote carcinogenesis in many systems, including microbe-driven colon cancer. Additional sources of IL17, such as gammadelta T cells, become available under inflammatory conditions, but their contributions to cancer development are unclear. In this study, we modeled Th17-driven colon tumorigenesis by colonizing Min(Ap) (c+/-) mice with the human gut bacterium, enterotoxigenic Bacteroides fragilis (ETBF), to investigate the link between inflammation and colorectal cancer. We found that ablating Th17 cells by knocking out Stat3 in CD4(+) T cells delayed tumorigenesis, but failed to suppress the eventual formation of colonic tumors. However, IL17 blockade significantly attenuated tumor formation, indicating a critical requirement for IL17 in tumorigenesis, but from a source other than Th17 cells. Notably, genetic ablation of gammadelta T cells in ETBF-colonized Th17-deficient Min mice prevented the late emergence of colonic tumors. Taken together, these findings support a redundant role for adaptive Th17 cell- and innate gammadeltaT17 cell-derived IL17 in bacteria-induced colon carcinogenesis, stressing the importance of therapeutically targeting the cytokine itself rather than its cellular sources. Cancer Res; 76(8); 2115-24. (c)2016 AACR. PMID- 26880803 TI - Deletion of Interstitial Genes between TMPRSS2 and ERG Promotes Prostate Cancer Progression. AB - TMPRSS2-ERG gene fusions that occur frequently in human prostate cancers can be generated either through insertional chromosomal rearrangement or by intrachromosomal deletion. Genetically, a key difference between these two mechanisms is that the latter results in deletion of a ~3-Mb interstitial region containing genes with unexplored roles in prostate cancer. In this study, we characterized two mouse models recapitulating TMPRSS2-ERG insertion or deletion events in the background of prostate-specific PTEN deficiency. We found that only the mice that lacked the interstitial region developed prostate adenocarcinomas marked by poor differentiation and epithelial-to-mesenchymal transition. Mechanistic investigations identified several interstitial genes, including Ets2 and Bace2, whose reduced expression correlated in the gene homologs in human prostate cancer with biochemical relapse and lethal disease. Accordingly, PTEN deficient mice with prostate-specific knockout of Ets2 exhibited marked progression of prostate adenocarcinomas that was partly attributed to activation of MAPK signaling. Collectively, our findings established that Ets2 is a tumor suppressor gene in prostate cancer, and its loss along with other genes within the TMPRSS2-ERG interstitial region contributes to disease progression. Cancer Res; 76(7); 1869-81. (c)2016 AACR. PMID- 26880804 TI - Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer. AB - Nonlethal exposure to ionizing radiation (IR) is a public concern due to its known carcinogenic effects. Although latency periods for IR-induced neoplasms are relatively long, the ability to detect cancer as early as possible is highly advantageous for effective therapeutic intervention. Therefore, we hypothesized that metabolites in the urine from mice exposed to total body radiation (TBI) would predict for the presence of cancer before a palpable mass was detected. In this study, we exposed mice to 0 or 5.4 Gy TBI, collected urine samples periodically over 1 year, and assayed urine metabolites by using mass spectrometry. Longitudinal data analysis within the first year post-TBI revealed that cancers, including hematopoietic, solid, and benign neoplasms, could be distinguished by unique urinary signatures as early as 3 months post-TBI. Furthermore, a distinction among different types of malignancies could be clearly delineated as early as 3 months post-TBI for hematopoietic neoplasms, 6 months for solid neoplasms, and by 1 year for benign neoplasms. Moreover, the feature profile for radiation-exposed mice 6 months post-TBI was found to be similar to nonirradiated control mice at 18 months, suggesting that TBI accelerates aging. These results demonstrate that urine feature profiles following TBI can identify cancers in mice prior to macroscopic detection, with important implications for the early diagnosis and treatment. PMID- 26880808 TI - Tobacco Causes Human Cancers--A Concept Founded on Epidemiology and an Insightful Experiment Now Requires Translation Worldwide. AB - The recognition that tobacco smoke is carcinogenic led to the most significant and successful effort at reducing cancer incidence in human history. A major milestone of this effort was the publication in Cancer Research by Wynder and colleagues, which demonstrated the ability of tobacco tars to produce tumors in mice. This study provided a powerful link between the epidemiology of cancer and mechanisms of carcinogenesis. This commentary asserts that we have a moral obligation to translate our success in reducing lung cancer in the United States to the 1.25 billion smokers throughout the rest of the world. See related article by Wynder et al., Cancer Res 1953;13:855-64. PMID- 26880805 TI - KLF4-Mediated Suppression of CD44 Signaling Negatively Impacts Pancreatic Cancer Stemness and Metastasis. AB - KLF4 and CD44 regulate cancer cell stemness, but their precise functions and roles in metastatic progression are not well understood. In this study, we used both inducible and genetic engineering approaches to assess whether the activities of these two factors intersect in pancreatic cancer. We found that genetic ablation of Klf4 in pancreatic cancer cells isolated from Klf4(flox/flox) mice drastically increased CD44 expression and promoted the acquisition of stem like properties, whereas tetracycline-inducible expression of KLF4 suppressed these properties in vitro and in vivo Further mechanistic investigation revealed that KLF4 bound to the CD44 promoter to negatively regulate transcription and also the expression of the CD44 variant. Moreover, in human pancreatic ductal adenocarcinoma (PDAC) tissues, the expression patterns of KLF4 and CD44 were mutually exclusive, and this inverse relationship was particularly striking in human metastatic pancreatic tumors and in autochthonous mouse models of PDAC. Taken together, our findings demonstrate that KLF4 acts as a tumor suppressor in PDAC cells that restricts metastatic behaviors through direct negative regulation of CD44, providing support for the clinical investigation of therapeutic approaches focusing on targeted KLF4 activation in advanced tumors. Cancer Res; 76(8); 2419-31. (c)2016 AACR. PMID- 26880809 TI - A Retrospective: On Clinical Studies with 5-Fluorouracil. PMID- 26880810 TI - Correction: Tumor Angiogenesis Mediated by Myeloid Cells Is Negatively Regulated by CEACAM1. PMID- 26880806 TI - At the Crossroads of Cancer Stem Cells, Radiation Biology, and Radiation Oncology. AB - Reports that a small subset of tumor cells initiate and sustain tumor growth, are resistant to radiation and drugs, and bear specific markers have led to an explosion of cancer stem cell research. These reports imply that the evaluation of therapeutic response by changes in tumor volume is misleading, as volume changes reflect the response of the sensitive rather than the resistant tumorigenic cell population. The reports further suggest that the marker-based selection of the tumor cell population will facilitate the development of radiation treatment schedules, sensitizers, and drugs that specifically target the resistant tumorigenic cells that give rise to treatment failure. This review presents evidence that contests the observations that cancer stem cell markers reliably identify the subset of tumor cells that sustain tumor growth and that the marker-identified population is radioresistant relative to the marker negative cells. Experimental studies show that cells and tumors that survive large radiation doses are not more radioresistant than unirradiated cells and tumors, and also show that the intrinsic radiosensitivity of unsorted colony forming tumor cells, in combination with the fraction of unsorted tumor cells that are tumor initiating, predicts tumor radiocurability. PMID- 26880811 TI - Tertiary hyperparathyroidism presenting as posterior reversible encephalopathy syndrome. PMID- 26880812 TI - ABCD2 score and secondary stroke prevention: Meta-analysis and effect per 1,000 patients triaged. PMID- 26880813 TI - Teaching NeuroImages: Red forehead dot syndrome and migraine revisited. PMID- 26880814 TI - Clinical Reasoning: A 62-year-old woman with bizarre behavior and recurrent episodes of behavioral arrest. PMID- 26880815 TI - Clinical Reasoning: A 37-year-old man with multiple cranial neuropathies. PMID- 26880817 TI - Correction. PMID- 26880816 TI - Teaching NeuroImages: MRI findings of biotin-responsive basal ganglia disease before and after treatment. PMID- 26880818 TI - Pheophytinase Knockdown Impacts Carbon Metabolism and Nutraceutical Content Under Normal Growth Conditions in Tomato. AB - Although chlorophyll (Chl) degradation is an essential biochemical pathway for plant physiology, our knowledge regarding this process still has unfilled gaps. Pheophytinase (PPH) was shown to be essential for Chl breakdown in dark-induced senescent leaves. However, the catalyzing enzymes involved in pigment turnover and fruit ripening-associated degreening are still controversial. Chl metabolism is closely linked to the biosynthesis of other isoprenoid-derived compounds, such as carotenoids and tocopherols, which are also components of the photosynthetic machinery. Chls, carotenoids and tocopherols share a common precursor, geranylgeranyl diphosphate, produced by the plastidial methylerythritol 4 phosphate (MEP) pathway. Additionally, the Chl degradation-derived phytol can be incorporated into tocopherol biosynthesis. In this context, tomato turns out to be an interesting model to address isoprenoid-metabolic cross-talk since fruit ripening combines degreening and an intensely active MEP leading to carotenoid accumulation. Here, we investigate the impact of PPH deficiency beyond senescence by the comprehensive phenotyping of SlPPH-knockdown tomato plants. In leaves, photosynthetic parameters indicate altered energy usage of excited Chl. As a mitigatory effect, photosynthesis-associated carotenoids increased while tocopherol content remained constant. Additionally, starch and soluble sugar profiles revealed a distinct pattern of carbon allocation in leaves that suggests enhanced sucrose exportation. The higher levels of carbohydrates in sink organs down-regulated carotenoid biosynthesis. Additionally, the reduction in Chl derived phytol recycling resulted in decreased tocopherol content in transgenic ripe fruits. Summing up, tocopherol and carotenoid metabolism, together with the antioxidant capacity of the hydrophilic and hydrophobic fractions, were differentially affected in leaves and fruits of the transgenic plants. Thus, in tomato, PPH plays a role beyond senescence-associated Chl degradation that, when compromised, affects isoprenoid and carbon metabolism which ultimately alters the fruit's nutraceutical content. PMID- 26880819 TI - Involvement of Potassium Transport Systems in the Response of Synechocystis PCC 6803 Cyanobacteria to External pH Change, High-Intensity Light Stress and Heavy Metal Stress. AB - The unicellular photosynthetic cyanobacterium, able to survive in varying environments, is the only prokaryote that directly converts solar energy and CO2 into organic material and is thus relevant for primary production in many ecosystems. To maintain the intracellular and intrathylakoid ion homeostasis upon different environmental challenges, the concentration of potassium as a major intracellular cation has to be optimized by various K(+)uptake-mediated transport systems. We reveal here the specific and concerted physiological function of three K(+)transporters of the plasma and thylakoid membranes, namely of SynK (K(+)channel), KtrB (Ktr/Trk/HKT) and KdpA (Kdp) in Synechocystis sp. strain PCC 6803, under specific stress conditions. The behavior of the wild type, single, double and triple mutants was compared, revealing that only Synk contributes to heavy metal-induced stress, while only Ktr/Kdp is involved in osmotic and salt stress adaptation. With regards to pH shifts in the external medium, the Kdp/Ktr uptake systems play an important role in the adaptation to acidic pH. Ktr, by affecting the CO2 concentration mechanism via its action on the bicarbonate transporter SbtA, might also be responsible for the observed effects concerning high-light stress and calcification. In the case of illumination with high intensity light, a synergistic action of Kdr/Ktp and SynK is required in order to avoid oxidative stress and ensure cell viability. In summary, this study dissects, using growth tests, measurement of photosynthetic activity and analysis of ultrastructure, the physiological role of three K(+)transporters in adaptation of the cyanobacteria to various environmental changes. PMID- 26880820 TI - When is a mass not a mass? An unusual presentation of prominent crista terminalis. AB - This case report describes a patient in whom echocardiography showed borderline left ventricular hypertrophy and a mass adjacent to the right atrial wall. This naturally caused some concern as the differential diagnoses included that of a right atrial myxoma and further investigations were organised. A subsequent cardiac MRI revealed this thickening to be a prominent crista terminalis. The crista terminalis is a variant of normal anatomical structures within the right atrium, which mimics an atrial mass. PMID- 26880821 TI - Perianal melanoma with a BRAF gene mutation in a young Portuguese Roma native. AB - A case of a young man diagnosed with perianal nodular melanoma with a gene mutation, accompanied by regional and pulmonary metastases on initial presentation, and later on with hepatic and bone involvement, is presented. The patient underwent wide local excision but was unresponsive to dacarbazine. Targeted therapy with vemurafenib had shown clinical improvement for a 5-month duration until he showed signs of disease progression. Just after the shift of adjuvant therapy to ipilimumab, he was diagnosed with multiple cerebral metastases that eventually led to his demise 6 months after initiation of vemurafenib, having had a 12-month survival period from the time of initial melanoma diagnosis. PMID- 26880822 TI - Multiple carpometacarpal dislocations and an associated fracture of the hamate: an uncommon injury. AB - Dislocation of the four ulnar carpometacarpal (CMC) joints with a concurrent fracture of the hamate is a rare injury, with a paucity of published cases. A great force is required to dislocate a CMC joint. Diagnosis can easily be missed, due to other serious associated injuries. Appropriate treatment of CMC joint dislocations usually leads to excellent outcomes. We present a case of dorsal dislocation of the four ulnar CMC joints after punching a wall. The injury was treated with a closed reduction and percutaneous transfixation with Kirschner wires. Despite the extensive injury, the functional result was good (full and painless range of motion) at 12 weeks of follow-up. PMID- 26880823 TI - Recovery of renal function after long-term dialysis and resolution of cardiomyopathy in a patient with aHUS receiving eculizumab. AB - We present the case of a 18-month-old girl with renal and cardiac manifestations of atypical haemolytic uraemic syndrome (aHUS), and a novel complement factor H mutation. Transient haematological remission was achieved with intensive plasmapheresis, but cardiac function deteriorated and renal function was not restored. Initiation of eculizumab after 6 months of dialysis significantly improved organ function. At 43 months after presentation, haematological values had normalised and cardiac function had improved. Dialysis was discontinued after 10 months (the longest reported time in a patient with aHUS) and the estimated glomerular filtration rate had recovered to 70 mL/min/1.73 m(2). In conclusion, treatment of aHUS with eculizumab, even after long-term dialysis, can significantly improve renal function. Discontinuation of dialysis and resolution of cardiac function has implications on the potential recovery and treatment choice of such patients. Earlier initiation of eculizumab, however, might have prevented the irreversible renal sclerosis and cardiac dysfunction. PMID- 26880824 TI - Dysuria and fever in a young woman diagnosed as having inflammatory myofibroblastic tumour of the urinary bladder. AB - A 38-year-old woman presented with dysuria and fever. Her medical and family histories were unremarkable. CT scan of the abdomen revealed a polypoid mass of 4*2.6*2.2 cm. Her cystoscopy showed a 4*2 cm solid broad-based growth at trigone of the urinary bladder. She underwent transurethral resection of the urinary bladder tumour (TURBT). Histopathology revealed a poorly circumscribed proliferation of spindle cells arranged in a haphazard and fascicular manner along with many traversing blood vessels in a myxoid and hyalinised stroma. Immunohistochemistry was positive for anaplastic lymphoma kinase-1, smooth muscle actin, CD10, cytokeratin and desmin; and negative for CD34 and S-100 protein. Ki 67 proliferative index in the tumour was <1%. The patient was diagnosed as having inflammatory myofibroblastic tumour of the urinary bladder. After TURBT, her fever and urinary symptoms resolved. Her 1-month postoperative period was uneventful. She has been advised regular follow-up. PMID- 26880825 TI - Long-term follow-up of unsuccessful coil embolisation in Osler-Weber-Rendu syndrome. PMID- 26880826 TI - Radiographically occult intrasinusoidal liver metastases leading to hepatic failure in a case of breast cancer. AB - The liver is one of the commonest sites of metastatic involvement in breast cancer, usually evident as focal lesions on imaging tests. Rarely, the pattern of metastatic spread is so diffuse that it remains radiologically occult. Such patients usually present with signs of hepatic insufficiency without any focal lesions on liver imaging. In such cases, liver biopsy is required to make a definitive diagnosis. We report a case of a 56-year-old postmenopausal woman with metastatic breast cancer who presented with subacute progressive liver failure. Repeated imaging of the liver was normal or non-descript. Liver biopsy finally established the diagnosis of intrasinusoidal metastases from breast cancer. PMID- 26880827 TI - Lhermitte-Duclos disease. PMID- 26880828 TI - Lipschutz ulcers: uncommon diagnosis of vulvar ulcerations. PMID- 26880829 TI - Easily missed fracture: distal radius and concomitant proximal ulna. PMID- 26880830 TI - Large apical thrombus due to Takotsubo cardiomyopathy. PMID- 26880831 TI - Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP positive rheumatoid arthritis patients: Association with disease activity and inflammatory markers. AB - OBJECTIVE: To quantify peptidylarginine deiminase 2 (PAD2) in SF of RA patients and OA patients, and to determine the association between PAD2 levels, disease activity and inflammatory markers in RA. METHODS: Blood and SF samples were obtained from 39 RA patients and 40 patients with OA. PAD2 content and PAD activity were measured by means of in-house assays. TNF-alpha, IL-1beta, IL-6, IL 8, IL-10 and IL-12 were measured using flow cytometry. RESULTS: PAD2 levels and PAD activity were higher in SF from RA than OA patients (P < 0.0001 and P = 0.03, respectively), as were all cytokine levels (P < 0.0001-0.05). SF PAD2 levels were higher among anti-CCP-positive patients than among anti-CCP-negative patients (P = 0.005). PAD2 levels in SF from RA patients correlated with disease activity, as assessed by DAS28 (P < 0.005). Moreover, SF PAD2 levels correlated with circulating CRP and anti-CCP levels (P < 0.0006), as well as with leucocyte count, IL-6, IL-8 and IL-10 levels in SF (P < 0.0001-0.02). PAD activity in SF was higher in RA patients than in OA patients, and correlated with PAD2 concentration. CONCLUSION: Extracellular PAD2 levels in SF correlate with disease activity in RA patients. Anti-CCP-positive RA patients have higher PAD2 levels in SF than anti-CCP-negative RA patients and OA patients. Since we could demonstrate enzymatically active PADs in SF, we propose that free, extracellular PAD is of pathogenic relevance. PMID- 26880832 TI - The relationship between skin symptoms and the scleroderma modification of the health assessment questionnaire, the modified Rodnan skin score, and skin pathology in patients with systemic sclerosis. AB - OBJECTIVE: To determine how well skin symptoms considered specific to SSc are captured by patient reported outcomes currently used for assessing patients with SSc, the SHAQ, or skin disease, the Skindex-29; and how well these symptoms correlate with the extent of skin disease on physical exam and skin pathology. METHODS: SSc patients completed the scleroderma modification of the Health Assessment Questionnaire (SHAQ), Skindex-29 and a Skin Symptom Assessment questionnaire developed for this study. Correlations were assessed between the Skin Symptom Assessment and SHAQ, Skindex-29, modified Rodnan skin score, and skin pathological features including myofibroblast staining completed on the same date. RESULTS: Tight, hard and rigid/stiff skin symptoms correlated moderately highly with the modified Rodnan skin score (r = 0.445, P = 0.0008; r = 0.486, P = 0.0002; and r = 0.488, P = 0.0002, respectively). Tight skin symptoms correlated moderately with myofibroblast infiltration (r = 0.544, P = 0.0023) and hyalinized collagen (r = 0.442, P = 0.0164), while both hard and rigid/stiff skin correlated moderately with inflammation (r = 0.401, P = 0.0310 and r = 0.513, P = 0.0045), myofibroblast infiltration(r = 0.480, P = 0.0084 and r = 0.527, P = 0.0033) and hyalinized collagen (r = 0.453, P = 0.0137 and r = 0.478, P = 0.0087), while the SHAQ was not found to correlate with any of these pathological changes. In contrast, painful skin symptoms correlated moderately with the SHAQ (r = 0.413, P = 0.0073), and with the three domains of Skindex-29: Symptoms, Emotions and Functioning. Skindex-29 indicates that dcSSc patient skin symptoms are nearly as severe as those of patients with psoriasis or atopic dermatitis. CONCLUSION: Patient reported skin symptoms correlate with clinical and pathological measures in the skin. A validated patient reported skin symptom instrument might considerably improve evaluation of SSc skin disease. PMID- 26880833 TI - Communicating about ocean health: theoretical and practical considerations. AB - As anthropogenic stressors threaten the health of marine ecosystems, there is a need to better understand how the public processes and responds to information about ocean health. Recent studies of public perceptions about ocean issues report high concern but limited knowledge, prompting calls for information campaigns to mobilize public support for ocean restoration policy. Drawing on the literature from communication, psychology and related social science disciplines, we consider a set of social-cognitive challenges that researchers and advocates are likely to encounter when communicating with the public about ocean health and emerging marine diseases--namely, the psychological distance at which ocean issues are construed, the unfamiliarity of aquatic systems to many members of the public and the potential for marine health issues to be interpreted through politicized schemas that encourage motivated reasoning over the dispassionate consideration of scientific evidence. We offer theory-based strategies to help public outreach efforts address these challenges and present data from a recent experiment exploring the role of message framing (emphasizing the public health or environmental consequences of marine disease) in shaping public support for environmental policy. PMID- 26880834 TI - Managing marine mollusc diseases in the context of regional and international commerce: policy issues and emerging concerns. AB - Marine mollusc production contributes to food and economic security worldwide and provides valuable ecological services, yet diseases threaten these industries and wild populations. Although the infrastructure for mollusc aquaculture health management is well characterized, its foundations are not without flaws. Use of notifiable pathogen lists can leave blind spots with regard to detection of unlisted and emerging pathogens. Increased reliance on molecular tools has come without similar attention to diagnostic validation, raising questions about assay performance, and has been accompanied by a reduced emphasis on microscopic diagnostic expertise that could weaken pathogen detection capabilities. Persistent questions concerning pathogen biology and ecology promote regulatory paralysis that impedes trade and which could weaken biosecurity by driving commerce to surreptitious channels. Solutions that might be pursued to improve shellfish aquaculture health management include the establishment of more broad based surveillance programmes, wider training and use of general methods like histopathology to ensure alertness to emerging diseases, an increased focus on assay assessment and validation as fundamental to assay development, investment in basic research, and application of risk analyses to improve regulation. A continual sharpening of diagnostic tools and approaches and deepening of scientific knowledge is necessary to manage diseases and promote sustainable molluscan shellfish industries. PMID- 26880835 TI - Managing marine disease emergencies in an era of rapid change. AB - Infectious marine diseases can decimate populations and are increasing among some taxa due to global change and our increasing reliance on marine environments. Marine diseases become emergencies when significant ecological, economic or social impacts occur. We can prepare for and manage these emergencies through improved surveillance, and the development and iterative refinement of approaches to mitigate disease and its impacts. Improving surveillance requires fast, accurate diagnoses, forecasting disease risk and real-time monitoring of disease promoting environmental conditions. Diversifying impact mitigation involves increasing host resilience to disease, reducing pathogen abundance and managing environmental factors that facilitate disease. Disease surveillance and mitigation can be adaptive if informed by research advances and catalysed by communication among observers, researchers and decision-makers using information sharing platforms. Recent increases in the awareness of the threats posed by marine diseases may lead to policy frameworks that facilitate the responses and management that marine disease emergencies require. PMID- 26880836 TI - Lessons from sea louse and salmon epidemiology. AB - Effective disease management can benefit from mathematical models that identify drivers of epidemiological change and guide decision-making. This is well illustrated in the host-parasite system of sea lice and salmon, which has been modelled extensively due to the economic costs associated with sea louse infections on salmon farms and the conservation concerns associated with sea louse infections on wild salmon. Consequently, a rich modelling literature devoted to sea louse and salmon epidemiology has been developed. We provide a synthesis of the mathematical and statistical models that have been used to study the epidemiology of sea lice and salmon. These studies span both conceptual and tactical models to quantify the effects of infections on host populations and communities, describe and predict patterns of transmission and dispersal, and guide evidence-based management of wild and farmed salmon. As aquaculture production continues to increase, advances made in modelling sea louse and salmon epidemiology should inform the sustainable management of marine resources. PMID- 26880837 TI - Shifting white pox aetiologies affecting Acropora palmata in the Florida Keys, 1994-2014. AB - We propose 'the moving target hypothesis' to describe the aetiology of a contemporary coral disease that differs from that of its historical disease state. Hitting the target with coral disease aetiology is a complex pursuit that requires understanding of host and environment, and may lack a single pathogen solution. White pox disease (WPX) affects the Caribbean coral Acropora palmata. Acroporid serratiosis is a form of WPX for which the bacterial pathogen (Serratia marcescens) has been established. We used long-term (1994-2014) photographic monitoring to evaluate historical and contemporary epizootiology and aetiology of WPX affecting A. palmata at eight reefs in the Florida Keys. Ranges of WPX prevalence over time (0-71.4%) were comparable for the duration of the 20-year study. Whole colony mortality and disease severity were high in historical (1994 2004), and low in contemporary (2008-2014), outbreaks of WPX. Acroporid serratiosis was diagnosed for some historical (1999, 2003) and contemporary (2012, 2013) outbreaks, but this form of WPX was not confirmed for all WPX cases. Our results serve as a context for considering aetiology as a moving target for WPX and other coral diseases for which pathogens are established and/or candidate pathogens are identified. Coral aetiology investigations completed to date suggest that changes in pathogen, host and/or environment alter the disease state and complicate diagnosis. PMID- 26880840 TI - Improving marine disease surveillance through sea temperature monitoring, outlooks and projections. AB - To forecast marine disease outbreaks as oceans warm requires new environmental surveillance tools. We describe an iterative process for developing these tools that combines research, development and deployment for suitable systems. The first step is to identify candidate host-pathogen systems. The 24 candidate systems we identified include sponges, corals, oysters, crustaceans, sea stars, fishes and sea grasses (among others). To illustrate the other steps, we present a case study of epizootic shell disease (ESD) in the American lobster. Increasing prevalence of ESD is a contributing factor to lobster fishery collapse in southern New England (SNE), raising concerns that disease prevalence will increase in the northern Gulf of Maine under climate change. The lowest maximum bottom temperature associated with ESD prevalence in SNE is 12 degrees C. Our seasonal outlook for 2015 and long-term projections show bottom temperatures greater than or equal to 12 degrees C may occur in this and coming years in the coastal bays of Maine. The tools presented will allow managers to target efforts to monitor the effects of ESD on fishery sustainability and will be iteratively refined. The approach and case example highlight that temperature-based surveillance tools can inform research, monitoring and management of emerging and continuing marine disease threats. PMID- 26880838 TI - Infectious diseases of marine molluscs and host responses as revealed by genomic tools. AB - More and more infectious diseases affect marine molluscs. Some diseases have impacted commercial species including MSX and Dermo of the eastern oyster, QPX of hard clams, withering syndrome of abalone and ostreid herpesvirus 1 (OsHV-1) infections of many molluscs. Although the exact transmission mechanisms are not well understood, human activities and associated environmental changes often correlate with increased disease prevalence. For instance, hatcheries and large scale aquaculture create high host densities, which, along with increasing ocean temperature, might have contributed to OsHV-1 epizootics in scallops and oysters. A key to understanding linkages between the environment and disease is to understand how the environment affects the host immune system. Although we might be tempted to downplay the role of immunity in invertebrates, recent advances in genomics have provided insights into host and parasite genomes and revealed surprisingly sophisticated innate immune systems in molluscs. All major innate immune pathways are found in molluscs with many immune receptors, regulators and effectors expanded. The expanded gene families provide great diversity and complexity in innate immune response, which may be key to mollusc's defence against diverse pathogens in the absence of adaptive immunity. Further advances in host and parasite genomics should improve our understanding of genetic variation in parasite virulence and host disease resistance. PMID- 26880841 TI - Vibrio bacteria in raw oysters: managing risks to human health. AB - The human-pathogenic marine bacteria Vibrio vulnificus and V. parahaemolyticus are strongly correlated with water temperature, with concentrations increasing as waters warm seasonally. Both of these bacteria can be concentrated in filter feeding shellfish, especially oysters. Because oysters are often consumed raw, this exposes people to large doses of potentially harmful bacteria. Various models are used to predict the abundance of these bacteria in oysters, which guide shellfish harvest policy meant to reduce human health risk. Vibrio abundance and behaviour varies from site to site, suggesting that location specific studies are needed to establish targeted risk reduction strategies. Moreover, virulence potential, rather than simple abundance, should be also be included in future modeling efforts. PMID- 26880839 TI - Complementary approaches to diagnosing marine diseases: a union of the modern and the classic. AB - Linking marine epizootics to a specific aetiology is notoriously difficult. Recent diagnostic successes show that marine disease diagnosis requires both modern, cutting-edge technology (e.g. metagenomics, quantitative real-time PCR) and more classic methods (e.g. transect surveys, histopathology and cell culture). Here, we discuss how this combination of traditional and modern approaches is necessary for rapid and accurate identification of marine diseases, and emphasize how sole reliance on any one technology or technique may lead disease investigations astray. We present diagnostic approaches at different scales, from the macro (environment, community, population and organismal scales) to the micro (tissue, organ, cell and genomic scales). We use disease case studies from a broad range of taxa to illustrate diagnostic successes from combining traditional and modern diagnostic methods. Finally, we recognize the need for increased capacity of centralized databases, networks, data repositories and contingency plans for diagnosis and management of marine disease. PMID- 26880843 TI - Fishing diseased abalone to promote yield and conservation. AB - Past theoretical models suggest fishing disease-impacted stocks can reduce parasite transmission, but this is a good management strategy only when the exploitation required to reduce transmission does not overfish the stock. We applied this concept to a red abalone fishery so impacted by an infectious disease (withering syndrome) that stock densities plummeted and managers closed the fishery. In addition to the non-selective fishing strategy considered by past disease-fishing models, we modelled targeting (culling) infected individuals, which is plausible in red abalone because modern diagnostic tools can determine infection without harming landed abalone and the diagnostic cost is minor relative to the catch value. The non-selective abalone fishing required to eradicate parasites exceeded thresholds for abalone sustainability, but targeting infected abalone allowed the fishery to generate yield and reduce parasite prevalence while maintaining stock densities at or above the densities attainable if the population was closed to fishing. The effect was strong enough that stock and yield increased even when the catch was one-third uninfected abalone. These results could apply to other fisheries as the diagnostic costs decline relative to catch value. PMID- 26880842 TI - Reserves as tools for alleviating impacts of marine disease. AB - Marine protected areas can prevent over-exploitation, but their effect on marine diseases is less clear. We examined how marine reserves can reduce diseases affecting reef-building corals following acute and chronic disturbances. One year after a severe tropical cyclone, corals inside reserves had sevenfold lower levels of disease than those in non-reserves. Similarly, disease prevalence was threefold lower on reserve reefs following chronic exposure to terrestrial run off from a degraded river catchment, when exposure duration was below the long term site average. Examination of 35 predictor variables indicated that lower levels of derelict fishing line and injured corals inside reserves were correlated with lower levels of coral disease in both case studies, signifying that successful disease mitigation occurs when activities that damage reefs are restricted. Conversely, reserves were ineffective in moderating disease when sites were exposed to higher than average levels of run-off, demonstrating that reductions in water quality undermine resilience afforded by reserve protection. In addition to implementing protected areas, we highlight that disease management efforts should also target improving water quality and limiting anthropogenic activities that cause injury. PMID- 26880844 TI - Ochre star mortality during the 2014 wasting disease epizootic: role of population size structure and temperature. AB - Over 20 species of asteroids were devastated by a sea star wasting disease (SSWD) epizootic, linked to a densovirus, from Mexico to Alaska in 2013 and 2014. For Pisaster ochraceus from the San Juan Islands, South Puget Sound and Washington outer coast, time-series monitoring showed rapid disease spread, high mortality rates in 2014, and continuing levels of wasting in the survivors in 2015. Peak prevalence of disease at 16 sites ranged to 100%, with an overall mean of 61%. Analysis of longitudinal data showed disease risk was correlated with both size and temperature and resulted in shifts in population size structure; adult populations fell to one quarter of pre-outbreak abundances. In laboratory experiments, time between development of disease signs and death was influenced by temperature in adults but not juveniles and adult mortality was 18% higher in the 19 degrees C treatment compared to the lower temperature treatments. While larger ochre stars developed disease signs sooner than juveniles, diseased juveniles died more quickly than diseased adults. Unusual 2-3 degrees C warm temperature anomalies were coincident with the summer 2014 mortalities. We suggest these warm waters could have increased the disease progression and mortality rates of SSWD in Washington State. PMID- 26880846 TI - Marine disease impacts, diagnosis, forecasting, management and policy. PMID- 26880845 TI - Infectious diseases in oyster aquaculture require a new integrated approach. AB - Emerging diseases pose a recurrent threat to bivalve aquaculture. Recently, massive mortality events in the Pacific oyster Crassostrea gigas associated with the detection of a microvariant of the ostreid herpesvirus 1 (OsHV-1uVar) have been reported in Europe, Australia and New Zealand. Although the spread of disease is often viewed as a governance failure, we suggest that the development of protective measures for bivalve farming is presently held back by the lack of key scientific knowledge. In this paper, we explore the case for an integrated approach to study the management of bivalve disease, using OsHV-1 as a case study. Reconsidering the key issues by incorporating multidisciplinary science could provide a holistic understanding of OsHV-1 and increase the benefit of research to policymakers. PMID- 26880851 TI - Prospective assessment of a palliative care tool to predict one-year mortality in patients with acute coronary syndrome. AB - BACKGROUND: Identifying patients with acute coronary syndrome (ACS) who are approaching the end of life and who may not benefit from an aggressive interventional approach is important but clinically challenging. The Gold Standards Framework (GSF) prognostic guide was developed using multidimensional criteria to identify cancer patients who could benefit from end-of-life care. We assessed the utility of the GSF to predict one-year mortality in ACS patients. METHODS: ACS patients admitted between May 2012 and July 2013 at the three participating cardiac centres in Europe were enrolled. Patients were assessed during admission using the GSF, the Global Registry of Acute Coronary Events (GRACE) score, the age, creatinine, ejection fraction (ACEF) score and the New York Percutaneous Coronary Intervention (NY-PCI) risk score. The pre-specified primary outcome was all-cause mortality at one year; secondary outcomes were cardiovascular death, non-cardiovascular mortality, re-hospitalisation for ACS and re-hospitalisation for non-ACS causes. RESULTS: Six hundred and twenty-nine ACS patients were enrolled and one-year follow-up data was available for 626 patients. Fifty-two patients (8.3%) met GSF criteria for end-of-life care. These patients were older, predominantly female, had lower body mass index (BMI), and were less likely to receive angiography (75% vs 95%, p<0.001) and angioplasty (60% vs 77%, p=0.005) compared with patients who did not meet GSF criteria. Patients meeting GSF criteria had higher one-year all-cause mortality (42.3% vs 4.5%, p<0.001), cardiovascular mortality (15.4% vs 2.8%, p<0.001) and non cardiovascular mortality (26.9% vs 1.7%; p<0.001). Multivariate analysis confirmed that meeting GSF criteria independently predicted all-cause mortality. CONCLUSION: GSF is a multidimensional tool which may be used to identify ACS patients that are at high risk of death and may benefit from end-of-life care. PMID- 26880852 TI - Coronary flow improvement following unsuccessful primary percutaneous coronary intervention in ST-elevation myocardial infarction with diffuse ectatic coronary artery. AB - BACKGROUND: In ST-elevation myocardial infarction (STEMI) patients with diffuse ectatic coronary artery, extensive thrombi inhibit achievement of final successful revascularization of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow after primary percutaneous coronary intervention. However, clinical and angiographic outcomes of such patients are uncertain. The present study examined clinical and angiographic outcomes in STEMI incorporating giant coronary artery with diffuse ectasia. METHODS: Seven hundred and forty-four STEMI patients undergoing primary percutaneous coronary intervention were surveyed retrospectively. Culprit lesions in giant coronary artery with diffuse ectasia (Ectatic group, n=39) were investigated. Percutaneous coronary intervention success rate and angiographic or clinical outcomes at 360 days were compared with those of the Non-ectatic group ( n=705). RESULTS: Angiographic percutaneous coronary intervention success rate was significantly lower in the Ectatic group due to lower achievement of final TIMI grade 3 flow (53.8% vs. 92.9%, p<0.0001; 53.8% vs. 93.5%, p<0.0001, respectively). In follow-up angiography, 86% of the Ectatic group showed angiographic improvement from TIMI grade 2 or less immediately after percutaneous coronary intervention to TIMI grade 3 flow at follow-up. In contrast, angiographic improvement was observed in only 25% of cases in the Non-ectatic group. All-cause 360-day mortality was significantly lower in the ectatic group (2.6% vs. 14.5%, p=0.0361, respectively). CONCLUSION: In patients with STEMI in giant coronary artery with diffuse ectasia, achievement of TIMI grade 3 flow was significantly reduced immediately after percutaneous coronary intervention. However, improvement of coronary flow up to TIMI grade 3 was not uncommon at follow-up angiogram. Patients had low mortality despite low TIMI grade 3 achievement immediately after primary percutaneous coronary intervention. PMID- 26880853 TI - The Long Term Recovery of New Orleans' Population after Hurricane Katrina. AB - Hurricane Katrina created a catastrophe in the city of New Orleans when the storm surge caused the levee system to fail on August 29, 2005. The destruction of housing displaced hundreds of thousands of residents for varying lengths of time, often permanently. It also revealed gaps in our knowledge of how population is recovered after a disaster causes widespread destruction of urban infrastructure, housing and workplaces, and how mechanisms driving housing recovery often produce unequal social, spatial and temporal population recovery. In this article, I assemble social, spatial and temporal explanatory frameworks for housing and population recovery and then review research on mobility - both evacuation and migration - after Hurricane Katrina. The review reveals a need for a comprehensive social, spatial and temporal framework for explaining inequality in population recovery and displacement. It also shows how little is known about in migrants and permanent out-migrants after a disaster. PMID- 26880854 TI - Skin Autofluorescence in Systemic Sclerosis Is Related to the Disease and Vascular Damage: A Cross-Sectional Analytic Study of Comparative Groups. AB - Skin autofluorescence (AF), a relatively simple and time saving procedure, measures the accumulation of advanced glycation end (AGE) products. The importance in autoimmune rheumatic diseases, particularly, systemic sclerosis (SSc), has not been evaluated yet. The aim of our study was to examine the skin AF in the context of SSc patients and to analyse the relations between skin AF and other surrogate measures of atherosclerosis. Forty-seven patients with SSc and 47 healthy volunteers were included in this study as controls. Patients and controls underwent common carotid artery wall assessment, arterial stiffness and wave reflection measurements, laser Doppler measurements of capillary flow, assessment of endothelial function by brachial ultrasound, peripheral arterial tonometry, and AGE measurement by skin AF. Wall properties of the common carotid arteries and wave reflection measurements were not affected in these study patients compared to controls while measures reflecting small capillary flow were altered. The accumulation of AGE products measured by skin AF was more prominent in SSc patients than in healthy controls. AGE products' score was significantly associated with carotid radial pulse wave velocity, intima media/carotid artery diameter ratio, capillary flow percentage change during occlusion, and the disease itself in a multivariate linear analysis model. PMID- 26880855 TI - Comparison of Serum MicroRNA21 and Tumor Markers in Diagnosis of Early Non-Small Cell Lung Cancer. AB - OBJECTIVE: To compare the clinical value of serum microRNA21 (miR21) and other tumor markers in early diagnosis of non-small cell lung cancer (NSCLC). METHODS: Serums carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and miR21 were detected in 50 NSCLC cases and 60 healthy control individuals. RESULTS: Average serums miR21, CEA, NSE, and CYFRA21 1 levels were significantly higher in the case group than in control group (P < 0.01). Analysis of areas under the receiver operating characteristic (ROC) curve (AUC) revealed that CEA had the highest diagnostic efficiency for NSCLC. Serums miR21 and CYFRA21-1 levels were significantly lower at TNM stages I-II than stages III-IV (P < 0.05). Further, logistic multivariate regression analysis showed that the incidence of early NSCLC (TNM stages I-II) was correlated with serums CYFRA21-1 (OR = 1.076) and miR21 (OR = 2.473) levels (P < 0.05). By AUC analysis, miR21 had the highest diagnostic efficiency for early NSCLC, and single or combined detection of serums CYFRA21-1 and miR21 levels showed improved diagnostic efficiency for joint detection of both markers. CONCLUSIONS: Serum miR21 could serve as an important marker for auxiliary diagnosis of early NSCLC, while joint detection of serums miR21 and CYFRA21-1 levels could improve diagnostic efficiency. PMID- 26880856 TI - Circulating Glutamate and Taurine Levels Are Associated with the Generation of Reactive Oxygen Species in Paroxysmal Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia, but its proarrhythmic mechanism remains to be elucidated. Glutamate (Glu) and taurine (Tau) are present in the myocardium at substantially higher concentrations than in the plasma, suggesting their active role in myocardium. Here, we tested the hypothesis that the metabolism of Glu and Tau is altered in association with the generation of reactive oxygen species (ROS) in patients with AF. Fifty patients with paroxysmal AF and 50 control subjects without a history of AF were consecutively enrolled. Circulating Glu and Tau levels were measured and correlations between Glu/Tau and ROS levels were examined. Glu/Tau content was significantly higher in patients with AF versus controls (Glu: 79.2 +/- 23.9 versus 60.5 +/- 25.2 nmol/L; Tau: 78.8 +/- 19.8 versus 68.5 +/- 20.8 nmol/L; mean +/- standard deviation (SD), p < 0.001 for both). Glu/Tau levels also showed an independent association with AF by multiple logistic regression analysis. Glu and Tau levels both showed significant positive associations with plasma hydroperoxide concentrations. These data suggest a novel pathophysiological role of Glu and Tau in association with ROS production in paroxysmal AF, providing new insights into the elevated amino acid content in cardiac disease. PMID- 26880857 TI - Systemic Inflammatory Response Based on Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker in Bladder Cancer. AB - A growing body of evidence suggests that systemic inflammatory response (SIR) in the tumor microenvironment is closely related to poor oncologic outcomes in cancer patients. Over the past decade, several SIR-related hematological factors have been extensively investigated in an effort to risk-stratify cancer patients to improve treatment selection and to predict posttreatment survival outcomes in various types of cancers. In particular, one readily available marker of SIR is neutrophil-to-lymphocyte ratio (NLR), which can easily be measured on the basis of absolute neutrophils and absolute lymphocytes in a differential white blood cell count performed in the clinical setting. Many investigators have vigorously assessed NLR as a potential prognostic biomarker predicting pathological and survival outcomes in patients with urothelial carcinoma (UC) of the bladder. In this paper, we aim to present the prognostic role of NLR in patients with UC of the bladder through a thorough review of the literature. PMID- 26880858 TI - Executive Function and Temperamental Fear Concurrently Predict Deception in School-Aged Children. AB - The decision to intentionally withhold truthful information, or deception, is a key component of moral development and may be a precursor to more serious anti social tendencies. Two factors, executive function and temperamental fear are each thought to influence childhood deception. Few studies, however, have explored deception in relation to both of these factors simultaneously. This was the goal of the present study. Executive function, as measured by a working memory task, and temperamental fear, as measured via maternal report were assessed in relation to observed deceptive behavior among 6 - 9-year-old children (N = 43). Results showed that children displaying high working memory capacity and high temperamental fear were more likely to exhibit deceptive behavior. Implications for predictors of childhood deception and applications for moral education are discussed. PMID- 26880859 TI - Cox-2 Plays a Vital Role in the Impaired Anxiety Like Behavior in Colchicine Induced Rat Model of Alzheimer Disease. AB - The anxiety status is changed along with memory impairments in intracerebroventricular colchicine injected rat model of Alzheimer Disease (cAD) due to neurodegeneration, which has been indicated to be mediated by inflammation. Inducible cox-2, involved in inflammation, may have important role in the colchicine induced alteration of anxiety status. Therefore, the present study was designed to investigate the role of cox-2 on the anxiety behavior (response to novelty in an elevated open field space) of cAD by inhibiting it with three different doses (10, 20, and 30 mg) of etoricoxib (a cox-2 blocker) in two time points (14 and 21 days). The results showed anxiolytic behavior in cAD along with lower serum corticosterone level, both of which were recovered at all the doses of etoricoxib on day 21. On day 14 all of the anxiety parameters showed similar results to that of day 21 at high doses but not at 10 mg/kg body weight. Results indicate that the parameters of anxiety were dependent on neuronal circuitries that were probably sensitive to etoricoxib induced blocking of neurodegeneration. The present study showed that anxiolytic behavior in cADr is predominantly due to cox-2 mediated neuroinflammation induced neurodegeneration in the brain. PMID- 26880860 TI - Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study. AB - BACKGROUND: Severe traumatization induces a complex pathophysiology, driven by the patient's own immune system. The initial activation is a result of damage associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. METHODS: We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry. RESULTS: High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. CONCLUSION: Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well known secondary stage of impaired immune responsiveness in trauma patients. PMID- 26880861 TI - Inflammation of the Dental Pulp. PMID- 26880863 TI - Matrine Attenuates COX-2 and ICAM-1 Expressions in Human Lung Epithelial Cells and Prevents Acute Lung Injury in LPS-Induced Mice. AB - Matrine is isolated from Sophora flavescens and shows anti-inflammatory effects in macrophages. Here we evaluated matrine's suppressive effects on cyclooxygenase 2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expressions in lipopolysaccharide- (LPS-) stimulated human lung epithelial A549 cells. Additionally, BALB/c mice were given various matrine doses by intraperitoneal injection, and then lung injury was induced via intratracheal instillation of LPS. In LPS-stimulated A549 cells, matrine inhibited the productions of interleukin-8 (IL-8), monocyte chemotactic protein-1, and IL-6 and decreased COX 2 expression. Matrine treatment also decreased ICAM-1 protein expression and suppressed the adhesion of neutrophil-like cells to inflammatory A549 cells. In vitro results demonstrated that matrine significantly inhibited mitogen-activated protein kinase phosphorylation and decreased nuclear transcription factor kappa-B subunit p65 protein translocation into the nucleus. In vivo data indicated that matrine significantly inhibited neutrophil infiltration and suppressed productions of tumor necrosis factor-alpha and IL-6 in mouse bronchoalveolar lavage fluid and serum. Analysis of lung tissue showed that matrine decreased the gene expression of proinflammatory cytokines, chemokines, COX-2, and ICAM-1. Our findings suggest that matrine improved lung injury in mice and decreased the inflammatory response in human lung epithelial cells. PMID- 26880862 TI - Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF kappaB Pathway in Type 2 Diabetic db/db Mice. AB - The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-kappaB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-kappaB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-kappaB pathway. PMID- 26880865 TI - Prognostic Value of Adrenomedullin and Natriuretic Peptides in Uroseptic Patients Induced by Ureteroscopy. AB - The aim of this paper is to investigate whether urosepsis is related to irrigation pressure of ureteroscopy (URS) and evaluate the prognostic value of adrenomedullin (ADM) and atrial and brain natriuretic peptides (ANP and BNP) in URS-induced uroseptic patients. From July 2008 to October 2013, we enrolled 332 patients with untreated unilateral ureteral obstruction (UUO). The UUO group included three subgroups of, respectively, 118, 132, and 82 patients who underwent URS under intermittent stable irrigation pressure of, respectively, 80, 120, and 160 mmHg. The plasma concentrations of ADM, ANP, and BNP were measured in all subjects. URS was performed for all UUO patients; the values of the three peptides were measured again after URS. Irrigation pressure and stone size were independent risk factors of urosepsis. After URS, the plasma concentrations of ADM, ANP, and BNP were significantly higher in uroseptic patients. Moreover, the concentrations were significantly higher depending on the disease severity. Plasma concentrations of the three peptides were correlated with plasma ET concentration in the uroseptic patients. The areas under receiver operating characteristic (ROC) curve of ADM, ANP, and BNP for predicting urosepsis were 0.811, 0.728, and 0.764, respectively. In conclusion, ADM, along with ANP and BNP, is valuable for prognosis in urosepsis secondary to URS which is associated with irrigation pressure. PMID- 26880864 TI - Fostering Inflammatory Bowel Disease: Sphingolipid Strategies to Join Forces. AB - Complex sphingolipids are essential structural components of intestinal membranes, providing protection and integrity to the intestinal mucosa and regulating intestinal absorption processes. The role of sphingolipid signaling has been established in numerous cellular events, including intestinal cell survival, growth, differentiation, and apoptosis. A significant body of knowledge demonstrates that intestinal sphingolipids play a crucial role, as such and through their signaling pathways, in immunity and inflammatory disorders. In this review, we report on and discuss the current knowledge on the metabolism, signaling, and functional implications of sphingolipids in inflammatory bowel disease (IBD), focusing on the different aspects of sphingolipid actions on inflammatory responses and on the potential of sphingolipid-targeted molecules as anti-IBD therapeutic agents. PMID- 26880866 TI - A test of the facultative calibration/reactive heritability model of extraversion. AB - A model proposed by Lukaszewski and Roney (2011) suggests that each individual's level of extraversion is calibrated to other traits that predict the success of an extraverted behavioural strategy. Under 'facultative calibration', extraversion is not directly heritable, but rather exhibits heritability through its calibration to directly heritable traits ("reactive heritability"). The current study uses biometrical modelling of 1659 identical and non-identical twins and their siblings to assess whether the genetic variation in extraversion is calibrated to variation in facial attractiveness, intelligence, height in men and body mass index (BMI) in women. Extraversion was significantly positively correlated with facial attractiveness in both males (r=.11) and females (r=.18), but correlations between extraversion and the other variables were not consistent with predictions. Further, twin modelling revealed that the genetic variation in facial attractiveness did not account for a substantial proportion of the variation in extraversion in either males (2.4%) or females (0.5%). PMID- 26880867 TI - Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma. AB - Purpose. Patients with large >5 cm, high-grade resectable soft tissue sarcomas (STS) have the highest risk of distant metastases. Previously we have shown that dendritic cell (DC) based vaccines show consistent immune responses. Methods. This was a Phase I single institution study of neoadjuvant radiation with DC injections on 18 newly diagnosed high-risk STS patients. Neoadjuvant treatment consisted of 50 Gy of external beam radiation (EBRT), given in 25 fractions delivered five days/week, combined with four intratumoral injections of DCs followed by complete resection. The primary endpoint was to establish the immunological response to neoadjuvant therapy and obtain data on its clinical safety and outcomes. Results. There were no unexpected toxicities or serious adverse events. Twelve out of 18 (67%) patients were alive, of which an encouraging 11/18 (61%) were alive with no systemic recurrence over a period of 2 8 years. Favorable immunological responses correlated with clinical responses in some cases. Conclusions. This study provides clinical support to using dendritic cell injections along with radiation in sarcomas, which when used optimally in combination can help clinical outcomes in soft tissue sarcoma. Study registration number is NCT00365872. PMID- 26880868 TI - Characterization of Fatty Acids in Crenarchaeota by GC-MS and NMR. AB - Lipids composed of condensed isoprenyl units connected to glycerol backbones by ether linkages are a distinguishing feature of Archaea. Data suggesting that fatty acids with linear hydrocarbon chains are present in some Archaea have been available for decades. However, lack of genomic and biochemical evidence for the metabolic machinery required to synthesize and degrade fatty acids has left the field unclear on this potentially significant biochemical aspect. Because lipids are energy currency and cell signaling molecules, their presence in Archaea is significant for understanding archaeal biology. A recent large-scale bioinformatics analysis reignited the debate as to the importance of fatty acids in Archaea by presenting genetic evidence for the presence of enzymes required for anabolic and catabolic fatty acid metabolism across the archaeal domain. Here, we present direct biochemical evidence from gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy for the presence of fatty acids in two members of the Crenarchaeota, Sulfolobus solfataricus and Ignicoccus hospitalis. This is the first report providing biochemical data for the existence of fatty acids in these Crenarchaeota, opening new discussions on energy balance and the potential for the discovery of new thermostable enzymes for industry. PMID- 26880869 TI - Characterising protein/detergent complexes by triple-detection size-exclusion chromatography. AB - BACKGROUND: In vitro investigations of membrane proteins usually depend on detergents for protein solubilisation and stabilisation. The amount of detergent bound to a membrane protein is relevant to successful experiment design and data analysis but is often unknown. Triple-detection size-exclusion chromatography enables simultaneous separation of protein/detergent complexes and protein-free detergent micelles and determination of their molar masses in a straightforward and absolute manner. Size-exclusion chromatography is used to separate different species, while ultraviolet absorbance, static light scattering, and refractive index measurements allow molar mass determination of protein and detergent components. RESULTS: We refined standard experimental and data-analysis procedures for challenging membrane-protein samples that elude routine approaches. The general procedures including preparatory steps, measurements, and data analysis for the characterisation of both routine and complex samples in difficult solvents such as concentrated denaturant solutions are demonstrated. The applicability of the protocol but also its limitations and possible solutions are discussed, and an extensive troubleshooting section is provided. CONCLUSIONS: We established and validated a protocol for triple-detection size-exclusion chromatography that enables the inexperienced user to perform and analyse measurements of well-behaved protein/detergent complexes. More experienced users are provided with an example of a more sophisticated analysis procedure allowing mass determination under challenging separation conditions. PMID- 26880870 TI - A Tactile Sensor for Ultrasound Imaging Systems. AB - Medical ultrasound systems are capable of monitoring a variety of health conditions while avoiding invasive procedures. However this function is complicated by ultrasound contrast of the tissue varying with contact pressure exerted by the probe. The knowledge of the contact pressure is beneficial for a variety of screening and diagnostic procedures involving ultrasound. This paper introduces a solid-state sensor array which measures the contact pressure distribution between the probe and the tissue marginally affecting the ultrasound imaging capabilities. The probe design utilizes the dielectrostriction mechanism which relates the change in dielectric properties of the sensing layer to deformation. The concept, structure, fabrication, and performance of this sensor array are discussed. The prototype device is highly tolerant to overloads (>1 MPa tested) and provides stress measurements in the range of 0.14 to 10 kPa. Its loss of ultrasound transmissivity is less 3dB at 9 MHz ultrasound frequency. This performance is satisfactory for clinical and biomedical research in ultrasound image formation and interpretation, however for commercial product, a higher ultrasound transmissivity is desired. Directions for improving the sensor ultrasound transparency and electrical performance are discussed. The sensor array described in this paper has been developed specifically for ultrasound diagnosis during breast cancer screening. However, the same sensing mechanism, similar configuration and sensor array structure can be applied to other applications involving ultrasound tools for medical diagnostics. PMID- 26880872 TI - Solving the Traveling Salesman's Problem Using the African Buffalo Optimization. AB - This paper proposes the African Buffalo Optimization (ABO) which is a new metaheuristic algorithm that is derived from careful observation of the African buffalos, a species of wild cows, in the African forests and savannahs. This animal displays uncommon intelligence, strategic organizational skills, and exceptional navigational ingenuity in its traversal of the African landscape in search for food. The African Buffalo Optimization builds a mathematical model from the behavior of this animal and uses the model to solve 33 benchmark symmetric Traveling Salesman's Problem and six difficult asymmetric instances from the TSPLIB. This study shows that buffalos are able to ensure excellent exploration and exploitation of the search space through regular communication, cooperation, and good memory of its previous personal exploits as well as tapping from the herd's collective exploits. The results obtained by using the ABO to solve these TSP cases were benchmarked against the results obtained by using other popular algorithms. The results obtained using the African Buffalo Optimization algorithm are very competitive. PMID- 26880873 TI - EEG Classification for Hybrid Brain-Computer Interface Using a Tensor Based Multiclass Multimodal Analysis Scheme. AB - Electroencephalogram- (EEG-) based brain-computer interface (BCI) systems usually utilize one type of changes in the dynamics of brain oscillations for control, such as event-related desynchronization/synchronization (ERD/ERS), steady state visual evoked potential (SSVEP), and P300 evoked potentials. There is a recent trend to detect more than one of these signals in one system to create a hybrid BCI. However, in this case, EEG data were always divided into groups and analyzed by the separate processing procedures. As a result, the interactive effects were ignored when different types of BCI tasks were executed simultaneously. In this work, we propose an improved tensor based multiclass multimodal scheme especially for hybrid BCI, in which EEG signals are denoted as multiway tensors, a nonredundant rank-one tensor decomposition model is proposed to obtain nonredundant tensor components, a weighted fisher criterion is designed to select multimodal discriminative patterns without ignoring the interactive effects, and support vector machine (SVM) is extended to multiclass classification. Experiment results suggest that the proposed scheme can not only identify the different changes in the dynamics of brain oscillations induced by different types of tasks but also capture the interactive effects of simultaneous tasks properly. Therefore, it has great potential use for hybrid BCI. PMID- 26880874 TI - An Improved Cuckoo Search Optimization Algorithm for the Problem of Chaotic Systems Parameter Estimation. AB - This paper proposes an improved cuckoo search (ICS) algorithm to establish the parameters of chaotic systems. In order to improve the optimization capability of the basic cuckoo search (CS) algorithm, the orthogonal design and simulated annealing operation are incorporated in the CS algorithm to enhance the exploitation search ability. Then the proposed algorithm is used to establish parameters of the Lorenz chaotic system and Chen chaotic system under the noiseless and noise condition, respectively. The numerical results demonstrate that the algorithm can estimate parameters with high accuracy and reliability. Finally, the results are compared with the CS algorithm, genetic algorithm, and particle swarm optimization algorithm, and the compared results demonstrate the method is energy-efficient and superior. PMID- 26880875 TI - Forecasting SPEI and SPI Drought Indices Using the Integrated Artificial Neural Networks. AB - The presented paper compares forecast of drought indices based on two different models of artificial neural networks. The first model is based on feedforward multilayer perceptron, sANN, and the second one is the integrated neural network model, hANN. The analyzed drought indices are the standardized precipitation index (SPI) and the standardized precipitation evaporation index (SPEI) and were derived for the period of 1948-2002 on two US catchments. The meteorological and hydrological data were obtained from MOPEX experiment. The training of both neural network models was made by the adaptive version of differential evolution, JADE. The comparison of models was based on six model performance measures. The results of drought indices forecast, explained by the values of four model performance indices, show that the integrated neural network model was superior to the feedforward multilayer perceptron with one hidden layer of neurons. PMID- 26880871 TI - Insight into the Molecular Imaging of Alzheimer's Disease. AB - Alzheimer's disease is a complex neurodegenerative disease affecting millions of individuals worldwide. Earlier it was diagnosed only via clinical assessments and confirmed by postmortem brain histopathology. The development of validated biomarkers for Alzheimer's disease has given impetus to improve diagnostics and accelerate the development of new therapies. Functional imaging like positron emission tomography (PET), single photon emission computed tomography (SPECT), functional magnetic resonance imaging (fMRI), and proton magnetic resonance spectroscopy provides a means of detecting and characterising the regional changes in brain blood flow, metabolism, and receptor binding sites that are associated with Alzheimer's disease. Multimodal neuroimaging techniques have indicated changes in brain structure and metabolic activity, and an array of neurochemical variations that are associated with neurodegenerative diseases. Radiotracer-based PET and SPECT potentially provide sensitive, accurate methods for the early detection of disease. This paper presents a review of neuroimaging modalities like PET, SPECT, and selected imaging biomarkers/tracers used for the early diagnosis of AD. Neuroimaging with such biomarkers and tracers could achieve a much higher diagnostic accuracy for AD and related disorders in the future. PMID- 26880876 TI - FPGA-Based Stochastic Echo State Networks for Time-Series Forecasting. AB - Hardware implementation of artificial neural networks (ANNs) allows exploiting the inherent parallelism of these systems. Nevertheless, they require a large amount of resources in terms of area and power dissipation. Recently, Reservoir Computing (RC) has arisen as a strategic technique to design recurrent neural networks (RNNs) with simple learning capabilities. In this work, we show a new approach to implement RC systems with digital gates. The proposed method is based on the use of probabilistic computing concepts to reduce the hardware required to implement different arithmetic operations. The result is the development of a highly functional system with low hardware resources. The presented methodology is applied to chaotic time-series forecasting. PMID- 26880877 TI - Imbalanced Learning Based on Logistic Discrimination. AB - In recent years, imbalanced learning problem has attracted more and more attentions from both academia and industry, and the problem is concerned with the performance of learning algorithms in the presence of data with severe class distribution skews. In this paper, we apply the well-known statistical model logistic discrimination to this problem and propose a novel method to improve its performance. To fully consider the class imbalance, we design a new cost function which takes into account the accuracies of both positive class and negative class as well as the precision of positive class. Unlike traditional logistic discrimination, the proposed method learns its parameters by maximizing the proposed cost function. Experimental results show that, compared with other state of-the-art methods, the proposed one shows significantly better performance on measures of recall, g-mean, f-measure, AUC, and accuracy. PMID- 26880878 TI - A Modified Sparse Representation Method for Facial Expression Recognition. AB - In this paper, we carry on research on a facial expression recognition method, which is based on modified sparse representation recognition (MSRR) method. On the first stage, we use Haar-like+LPP to extract feature and reduce dimension. On the second stage, we adopt LC-K-SVD (Label Consistent K-SVD) method to train the dictionary, instead of adopting directly the dictionary from samples, and add block dictionary training into the training process. On the third stage, stOMP (stagewise orthogonal matching pursuit) method is used to speed up the convergence of OMP (orthogonal matching pursuit). Besides, a dynamic regularization factor is added to iteration process to suppress noises and enhance accuracy. We verify the proposed method from the aspect of training samples, dimension, feature extraction and dimension reduction methods and noises in self-built database and Japan's JAFFE and CMU's CK database. Further, we compare this sparse method with classic SVM and RVM and analyze the recognition effect and time efficiency. The result of simulation experiment has shown that the coefficient of MSRR method contains classifying information, which is capable of improving the computing speed and achieving a satisfying recognition result. PMID- 26880879 TI - Combining Review Text Content and Reviewer-Item Rating Matrix to Predict Review Rating. AB - E-commerce develops rapidly. Learning and taking good advantage of the myriad reviews from online customers has become crucial to the success in this game, which calls for increasingly more accuracy in sentiment classification of these reviews. Therefore the finer-grained review rating prediction is preferred over the rough binary sentiment classification. There are mainly two types of method in current review rating prediction. One includes methods based on review text content which focus almost exclusively on textual content and seldom relate to those reviewers and items remarked in other relevant reviews. The other one contains methods based on collaborative filtering which extract information from previous records in the reviewer-item rating matrix, however, ignoring review textual content. Here we proposed a framework for review rating prediction which shows the effective combination of the two. Then we further proposed three specific methods under this framework. Experiments on two movie review datasets demonstrate that our review rating prediction framework has better performance than those previous methods. PMID- 26880880 TI - Explore Interregional EEG Correlations Changed by Sport Training Using Feature Selection. AB - This paper investigated the interregional correlation changed by sport training through electroencephalography (EEG) signals using the techniques of classification and feature selection. The EEG data are obtained from students with long-time professional sport training and normal students without sport training as baseline. Every channel of the 19-channel EEG signals is considered as a node in the brain network and Pearson Correlation Coefficients are calculated between every two nodes as the new features of EEG signals. Then, the Partial Least Square (PLS) is used to select the top 10 most varied features and Pearson Correlation Coefficients of selected features are compared to show the difference of two groups. Result shows that the classification accuracy of two groups is improved from 88.13% by the method using measurement of EEG overall energy to 97.19% by the method using EEG correlation measurement. Furthermore, the features selected reveal that the most important interregional EEG correlation changed by training is the correlation between left inferior frontal and left middle temporal with a decreased value. PMID- 26880881 TI - The Study of Intelligent Vehicle Navigation Path Based on Behavior Coordination of Particle Swarm. AB - In the behavior dynamics model, behavior competition leads to the shock problem of the intelligent vehicle navigation path, because of the simultaneous occurrence of the time-variant target behavior and obstacle avoidance behavior. Considering the safety and real-time of intelligent vehicle, the particle swarm optimization (PSO) algorithm is proposed to solve these problems for the optimization of weight coefficients of the heading angle and the path velocity. Firstly, according to the behavior dynamics model, the fitness function is defined concerning the intelligent vehicle driving characteristics, the distance between intelligent vehicle and obstacle, and distance of intelligent vehicle and target. Secondly, behavior coordination parameters that minimize the fitness function are obtained by particle swarm optimization algorithms. Finally, the simulation results show that the optimization method and its fitness function can improve the perturbations of the vehicle planning path and real-time and reliability. PMID- 26880882 TI - A Motion Detection Algorithm Using Local Phase Information. AB - Previous research demonstrated that global phase alone can be used to faithfully represent visual scenes. Here we provide a reconstruction algorithm by using only local phase information. We also demonstrate that local phase alone can be effectively used to detect local motion. The local phase-based motion detector is akin to models employed to detect motion in biological vision, for example, the Reichardt detector. The local phase-based motion detection algorithm introduced here consists of two building blocks. The first building block measures/evaluates the temporal change of the local phase. The temporal derivative of the local phase is shown to exhibit the structure of a second order Volterra kernel with two normalized inputs. We provide an efficient, FFT-based algorithm for implementing the change of the local phase. The second processing building block implements the detector; it compares the maximum of the Radon transform of the local phase derivative with a chosen threshold. We demonstrate examples of applying the local phase-based motion detection algorithm on several video sequences. We also show how the locally detected motion can be used for segmenting moving objects in video scenes and compare our local phase-based algorithm to segmentation achieved with a widely used optic flow algorithm. PMID- 26880883 TI - Molecular Epidemiology of Enteric Adenovirus Gastroenteritis in under-Five-Year Old Children in Iran. AB - Background. Acute gastroenteritis is one of the major sources of morbidity and mortality among young children in developed and developing countries. The aim of this study was to determine the prevalence of human adenovirus- (HAdV-) 40 and HAdV-41 in children hospitalized with gastroenteritis in five different health centers of Iran. Methods. In a cross-sectional epidemiological study, we studied 2682 fecal specimens that were collected from children under the age of 5 years in five educational and therapeutic pediatric centers in Iran from February 2012 to February 2013. Samples were tested for HAdV-40 and HAdV-41, using a specific pair of primers in polymerase chain reaction (PCR) method. Results. HAdV-40 and HAdV-41 were detected in 132 (5.18%) of the patients with diarrhea. A significantly higher prevalence of HAdV-40 and HAdV-41 (58.3%) was observed in children under 12 months of age, compared to other age groups. The male to female ratio was 1.7. Conclusion. The results of this study demonstrated that HAdV-40 and HAdV-41 could be considered etiological agents for acute gastroenteritis among children in Iran. The PCR as a rapid test may increase the chance for a relatively mild course of the disease followed by a complete recovery and avoiding administration of unnecessary antibiotics. PMID- 26880884 TI - A Novel Diagnostic Aid for Detection of Intra-Abdominal Adhesions to the Anterior Abdominal Wall Using Dynamic Magnetic Resonance Imaging. AB - Introduction. Abdominal adhesions can cause serious morbidity and complicate subsequent operations. Their diagnosis is often one of exclusion due to a lack of a reliable, non-invasive diagnostic technique. Development and testing of a candidate technique are described below. Method. During respiration, smooth visceral sliding motion occurs between the abdominal contents and the walls of the abdominal cavity. We describe a technique involving image segmentation and registration to calculate shear as an analogue for visceral slide based on the tracking of structures throughout the respiratory cycle. The presence of an adhesion is attributed to a resistance to visceral slide resulting in a discernible reduction in shear. The abdominal movement due to respiration is captured in sagittal dynamic MR images. Results. Clinical images were selected for analysis, including a patient with a surgically confirmed adhesion. Discernible reduction in shear was observed at the location of the adhesion while a consistent, gradually changing shear was observed in the healthy volunteers. Conclusion. The technique and its validation show encouraging results for adhesion detection but a larger study is now required to confirm its potential. PMID- 26880885 TI - Role of S100 Proteins in Colorectal Carcinogenesis. AB - The family of S100 proteins represents 25 relatively small (9-13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-kappabeta signaling pathway, which plays a key role in the molecular pathogenesis especially of colitis associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy. PMID- 26880886 TI - Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients. AB - Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0-F2) or advanced (F3-F4) fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy. PMID- 26880887 TI - Functional Constipation and Constipation-Predominant Irritable Bowel Syndrome in the General Population: Data from the GECCO Study. AB - Background. The prevalence of constipation in the (German) population has been shown to be 14.9% in a telephone survey, but more detailed data are required to characterize the sociographics and clinical characteristics of persons with different types of functional constipation, either constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation with or without meeting Rome criteria. Methods. Of 2239 constipated individuals identified during the telephone interview, 1037 (46.3%) were willing to provide a postal address for a questionnaire, of which 589 (56.8%) returned the questionnaire, inquiring about sociographic data, clinical symptoms, and health care behavior related to constipation, as well as health-related quality-of-life (SF12). Subgroups of functionally constipated individuals were compared. Results. More than 50% of the respondents reported a somatic comorbid condition and/or regular medication intake that may contribute to constipation. We split the remaining individuals (N = 214) into three groups, matching Rome-criteria for IBS (IBS-C, n = 64) and for functional constipation (FC-R, n = 36) and FC not matching Rome criteria (n = 114). Nearly all sociographic and clinical characteristics were equal among them, and all individuals with constipation had similar and lowered QOL on the SF-12 physical health domain, but in IBS-C the scores were also significantly lower in comparison to FC-R and FC, in both the physical health and the mental health domain. Conclusion. Only a fraction of individuals with chronic constipation match Rome criteria for IBS-C or FC, but subgroups do not differ with respect to most other measures except quality-of-life profiles. PMID- 26880888 TI - Lifor Solution: An Alternative Preservation Solution in Small Bowel Transplantation. AB - Background and Objectives. The intestinal mucosa is extremely sensitive to ischemia. Better intestinal preservation is the first step to improve the results of intestinal transplantation. The aim of the study is to investigate the effect of cold Lifor solution on preservation of swine small bowel. Methods. Swine ileum segments (200 cm) were allotransplanted heterotopically after 9-hour cold storage with UW solution (group 1, n = 6), with Lifor solution (group 2, n = 6), or without storage (group 3, n = 6), respectively. After cold storage, mucosal adenosine triphosphate (ATP) concentrations and histopathologic analysis after preservation were performed. At day 7 after the transplantation, intestinal absorptive function was also observed. Results. After 9 h cold preservation, pathological changes, the content of ATP in the intestinal mucosa, and the intestinal absorptive function after transplantation in group 2 were similar to those of group 1. Conclusion. The effect of cold storage of swine small bowel with Lifor solution is similar to that of UW solution. It may provide additional rationale for further exploration of Lifor as an alternative preservation solution in small bowel transplantation. PMID- 26880889 TI - Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application. AB - Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID- 26880890 TI - Treatment with a Monoclonal Anti-IL-12p40 Antibody Induces Substantial Gut Microbiota Changes in an Experimental Colitis Model. AB - Background and Aim. Crohn's disease is associated with gut microbiota (GM) dysbiosis. Treatment with the anti-IL-12p40 monoclonal antibody (12p40-mAb) has therapeutic effect in Crohn's disease patients. This study addresses whether a 12p40-mAb treatment influences gut microbiota (GM) composition in mice with adoptive transfer colitis (AdTr-colitis). Methods. AdTr-colitis mice were treated with 12p40-mAb or rat-IgG2a or NaCl from days 21 to 47. Disease was monitored by changes in body weight, stool, endoscopic and histopathology scores, immunohistochemistry, and colonic cytokine/chemokine profiles. GM was characterized through DGGE and 16S rRNA gene-amplicon high-throughput sequencing. Results. Following 12p40-mAb treatment, most clinical and pathological parameters associated with colitis were either reduced or absent. GM was shifted towards a higher Firmicutes-to-Bacteroidetes ratio compared to rat-IgG2a treated mice. Significant correlations between 17 bacterial genera and biological markers were found. The relative abundances of the RF32 order (Alphaproteobacteria) and Akkermansia muciniphila were positively correlated with damaged histopathology and colonic inflammation. Conclusions. Shifts in GM distribution were observed with clinical response to 12p40-mAb treatment, whereas specific GM members correlated with colitis symptoms. Our study implicates that specific changes in GM may be connected with positive clinical outcomes and suggests preventing or correcting GM dysbiosis as a treatment goal in inflammatory bowel disease. PMID- 26880891 TI - Ultrasonic Dissection versus Conventional Dissection for Pancreatic Surgery: A Meta-Analysis. AB - Background. The role of ultrasonic dissection (UD) in pancreatic surgery remains controversial. The aim of this meta-analysis was to evaluate the clinical effect of UD in pancreatic surgery when compared with conventional dissection (CD). Materials and Methods. A comprehensive literature search was performed to identify eligible studies that compared UD with CD for pancreatic surgery in PubMed, EMBASE, Web of Science, and the Cochrane Library. Risk ratio (RR) or mean difference with 95% confidence interval (CI) was calculated. Results. Six studies were included with a total of 215 patients undergoing UD and 210 undergoing CD. In comparison with CD in distal pancreatectomy, UD was associated with lower rates of pancreatic fistula (RR = 0.46, 95% CI: 0.27-0.76) and abdominal abscess and shorter operation time and hospital stay (P < 0.05). In pancreaticoduodenectomy, there was no significant difference in pancreatic fistula rate between two groups (RR = 0.79, 95% CI: 0.48-1.29). However, the significantly less intraoperative blood loss and the transfused blood unit were found in patients receiving UD (P < 0.05). Conclusions. The results of this meta analysis show that, in comparison with CD, UD is associated with better perioperative outcomes in pancreatic surgery. PMID- 26880892 TI - A Retrospective Research of the Characteristic of Hypertriglyceridemic Pancreatitis in Beijing, China. AB - Aim. To investigate the characteristic of hypertriglyceridemic- (HTG-) induced pancreatitis (HTG pancreatitis). Methods. We reviewed 126 cases of HTG pancreatitis and 168 cases of biliary pancreatitis as control. Results. The HTG group mean age was younger than biliary group. The number of females was a little higher than males in both groups. There were 18 cases that were recurrent in HTG group and 11 in billiary group. The mean hospitalization times were 13.7 +/- 2.6 and 11.2 +/- 2.3 days in two groups. Six patients received apheresis in HTG group. The proportion of severe AP was 31.0% and 26.2%, mortality 1.6% and 1.2%, comorbidity of diabetes mellitus (DM) 20.6% and 6.5% in two groups. The number of complications of gastrointestinal (GI) bleeding, sepsis, and multiple organ dysfunction syndrome (MODS) in HTG group and biliary group was 1, 1, and 2 versus 4, 12, and 4. Conclusions. The proportion of recurrent and severe AP and comorbidity of DM of HTG group was higher than billiary group. The proportion of the complications of GI bleeding, sepsis, and MODS of HTG group was less than biliary group. Apheresis could effectively reduce serum TG levels soon. There was no significant difference of the mortality between two groups. PMID- 26880893 TI - MR Imaging in Diagnosis of Pelvic Floor Descent: Supine versus Sitting Position. AB - Introduction. Functional disorders of the pelvic floor represent have a significant impact on the quality of life. The advent of open-configuration systems allowed for the evaluation of defecation with MR imaging in sitting position. The purpose of the present study is to compare the results of static and dynamic pelvic MR performed in supine position versus sitting position, using a new MR prototype machine, in the diagnosis of pelvic floor descent. Materials and Methods. Thirty-one patients with pelvic floor disorders were enrolled, and underwent MR Defecography in supine position with 1.5 T closed magnet (MAGNETOM Symphony, Siemens, Germany) and in sitting position with a 0.25-Tesla open magnet system (G-Scan ESAOTE, Italy). Results. In rest and squeezing phases, positions of bladder, vagina, and ARJ were significantly different when the patient was imaged in supine versus sitting position. In the defecation phase, a significant difference for the bladder and vagina position was detected between the two exams whereas a significant difference for the ARJ was not found. A statistically significant difference exists when the pelvic floor descent is evaluated in sitting versus supine position. Conclusion. Our results show that MR Defecography in sitting position may represent a useful tool to correctly diagnose and grade the pelvic organ descent. PMID- 26880894 TI - Optimal Bowel Preparation for Video Capsule Endoscopy. AB - During video capsule endoscopy (VCE), several factors, such as air bubbles, food material in the small bowel, and delayed gastric and small bowel transit time, influence diagnostic yield, small bowel visualization quality, and cecal completion rate. Therefore, bowel preparation before VCE is as essential as bowel preparation before colonoscopy. To date, there have been many comparative studies, consensus, and guidelines regarding different kinds of bowel cleansing agents in bowel preparation for small bowel VCE. Presently, polyethylene glycol- (PEG-) based regimens are given primary recommendation. Sodium picosulphate-based regimens are secondarily recommended, as their cleansing efficacy is less than that of PEG-based regimens. Sodium phosphate as well as complementary simethicone and prokinetics use are considered. In this paper, we reviewed previous studies regarding bowel preparation for small bowel VCE and suggested optimal bowel preparation of VCE. PMID- 26880895 TI - Loss of CADM1/TSLC1 Expression Is Associated with Poor Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma. AB - Aims. We sought to determine the relationship between CADM1/TSLC1 expression and clinicopathological characteristics in patients with esophageal squamous cell carcinoma (ESCC) and the correlation with survival. Materials and Methods. Two hundred and ninety-three ESCC tissues and paired adjacent normal esophageal tissues were immunohistochemically assessed in this study. The association of CADM1/TSLC1 with clinicopathological parameters, as well as disease-free survival (DFS) and overall survival (OS), was determined based on the Kaplan-Meier method and Cox regression models. Results. CADM1/TSLC1 was detected in 236 (80.5%) tumor tissues and 19 (8.0%) paired adjacent normal esophageal tissues. Decreased CADM1/TSLC1 expression was correlated with more advanced histological grade. CADM1/TSLC1 negative tumors were more frequently observed in male cases than in female cases. DFS and OS in the CADM1/TSLC1 negative group were significantly shorter than those in the positive group, particularly in male patients with ESCC. Conclusion. Loss or reduction of CADM1/TSLC1 expression is associated with more advanced histological grade and predicts early recurrence and short survival duration. Thus, loss of CADM1/TSLC1 could be a prognostic factor that can be used to assess the risk of recurrence and survival. PMID- 26880896 TI - Efficacy of Tenofovir-Based Combination Therapy versus Tenofovir Monotherapy in Chronic Hepatitis B Patients Presenting with Suboptimal Responses to Pretreatment: A Meta-Analysis. AB - Background/Aims. It remains unclear whether tenofovir disoproxil fumarate- (TDF-) based combination therapy produces better outcomes than TDF monotherapy in chronic hepatitis B (CHB) patients. The aim of this study was to compare the efficacy of the two regimens by performing a meta-analysis. Methods. A comprehensive literature search was performed on the comparison of TDF-based combination therapy and monotherapy for CHB patients in the PubMed, Embase, Web of Science, and the Cochrane Libraries. Both dichotomous and continuous variables were extracted and pooled outcomes were expressed as risk ratio (RR) or standard mean difference (SMD). Results. Nine eligible studies (1089 subjects in total) were included in our analysis. The proportion of patients with undetectable HBV DNA at 24, 48, and 96 weeks were similar between the two comparable groups (62.5% versus 70.9%, P = 0.086; 78.1% versus 83.7%, P = 0.118; 86.4% versus 87.9%, P = 0.626, resp.). HBV DNA reduction, rates of ALT normalization, hepatitis B e antigen (HBeAg) loss, and HBeAg seroconversion were also similar between the two groups. Conclusions. On the current data, TDF-based combination therapy seemed to be no better than those achieved by monotherapy. Further studies are needed to verify this comparison. PMID- 26880897 TI - Preoperative Biliary Drainage in Cases of Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Chemotherapy and Surgery. AB - Objective. To elucidate the optimum preoperative biliary drainage method for patients with pancreatic cancer treated with neoadjuvant chemotherapy (NAC). Material and Methods. From January 2010 through December 2014, 20 patients with borderline resectable pancreatic cancer underwent preoperative biliary drainage and NAC with a plastic or metallic stent and received NAC at Hiroshima University Hospital. We retrospectively analyzed delayed NAC and complication rates due to biliary drainage, effect of stent type on perioperative factors, and hospitalization costs from diagnosis to surgery. Results. There were 11 cases of preoperative biliary drainage with plastic stents and nine metallic stents. The median age was 64.5 years; delayed NAC occurred in 9 cases with plastic stent and 1 case with metallic stent (p = 0.01). The complication rates due to biliary drainage were 0% (0/9) with metallic stents and 72.7% (8/11) with plastic stents (p = 0.01). Cumulative rates of complications determined with the Kaplan-Meier method on day 90 were 60% with plastic stents and 0% with metallic stents (log rank test, p = 0.012). There were no significant differences between group in perioperative factors or hospitalization costs from diagnosis to surgery. Conclusions. Metallic stent implantation may be effective for preoperative biliary drainage for pancreatic cancer treated with NAC. PMID- 26880898 TI - Do NSAIDs and ASA Cause More Upper Gastrointestinal Bleeding in Elderly than Adults? AB - Purpose. NSAIDs and ASA may cause upper gastrointestinal bleeding (UGIB) both in adults and in elderly. There is no study that compares this increased bleeding risk between adult and elderly subjects. Methods. A total of 524 patients with UGIB were included in this study. The data of patients were, respectively, analyzed. Results. NSAIDs and ASA-associated UGIB rates were similar between <65 years (345 patients) (group 1) and >=65 years (179 patients) (group 2) (28.4% versus 23.5%, p = 0.225 and 13% versus 19%, p = 0.071, resp.). Warfarin associated UGIB was found significantly higher in group 2 than group 1. Elderly patients with NSAID-associated UGIB had significantly higher length of stay (LoS) and CoH than adult patients with NSAID-associated UGIB (p = 0.002 and 0.001, resp.). Elderly patients with ASA-associated UGIB had significantly higher CoH than adult patients with NSAID-associated UGIB. Conclusions. Using NSAIDs without gastroprotective drugs or using ASA with gastroprotective drugs in elderly patients is as safe as in adult patients. Not only should adding gastroprotective drugs to ASA or NSAID be based on their risk of UGIB, but the cost of hospitalization of ASA or NSAID-associated UGIB should be considered. PMID- 26880899 TI - Postoperative Albumin Drop Is a Marker for Surgical Stress and a Predictor for Clinical Outcome: A Pilot Study. AB - Background. Surgical stress during major surgery may be related to adverse clinical outcomes and early quantification of stress response would be useful to allow prompt interventions. The aim of this study was to evaluate the acute phase protein albumin in the context of the postoperative stress response. Methods. This prospective pilot study included 70 patients undergoing frequent abdominal procedures of different magnitude. Albumin (Alb) and C-reactive protein (CRP) levels were measured once daily starting the day before surgery until postoperative day (POD) 5. Maximal Alb decrease (Alb Delta min) was correlated with clinical parameters of surgical stress, postoperative complications, and length of stay. Results. Albumin values dropped immediately after surgery by about 10 g/L (42.2 +/- 4.5 g/L preoperatively versus 33.8 +/- 5.3 g/L at day 1, P < 0.001). Alb Delta min was correlated with operation length (Pearson rho = 0.470, P < 0.001), estimated blood loss (rho = 0.605, P < 0.001), and maximal CRP values (rho = 0.391, P = 0.002). Alb Delta min levels were significantly higher in patients having complications (10.0 +/- 5.4 versus 6.1 +/- 5.2, P = 0.005) and a longer hospital stay (rho = 0.285, P < 0.020). Conclusion. Early postoperative albumin drop appeared to reflect the magnitude of surgical trauma and was correlated with adverse clinical outcomes. Its promising role as early marker for stress response deserves further prospective evaluation. PMID- 26880900 TI - Results of Medium Seventeen Years' Follow-Up after Laparoscopic Choledochotomy for Ductal Stones. AB - Introduction. In a previously published article the authors reported the long term follow-up results in 138 consecutive patients with gallstones and common bile duct (CBD) stones who underwent laparoscopic transverse choledochotomy (TC) with T-tube biliary drainage and laparoscopic cholecystectomy (LC). Aim of this study is to evaluate the results at up to 23 years of follow-up in the same series. Methods. One hundred twenty-one patients are the object of the present study. Patients were evaluated by clinical visit, blood assay, and abdominal ultrasound. Symptomatic patients underwent cholangio-MRI, followed by endoscopic retrograde cholangiopancreatography (ERCP) as required. Results. Out of 121 patients, 61 elderly patients died from unrelated causes. Fourteen patients were lost to follow-up. In the 46 remaining patients, ductal stone recurrence occurred in one case (2,1%) successfully managed by ERCP with endoscopic sphincterotomy. At a mean follow-up of 17.1 years no other patients showed signs of bile stasis and no patient showed any imaging evidence of CBD stricture at the site of choledochotomy. Conclusions. Laparoscopic transverse choledochotomy with routine T-tube biliary drainage during LC has proven to be safe and effective at up to 23 years of follow-up, with no evidence of CBD stricture when the procedure is performed with a correct technique. PMID- 26880901 TI - Risk of Gastrointestinal Bleeding with Rivaroxaban: A Comparative Study with Warfarin. AB - Introduction. The risk of gastrointestinal (GI) bleeding with rivaroxaban has not been studied extensively. The aim of our study was to assess this risk in comparison to warfarin. Methods. We examined the medical records for patients who were started on rivaroxaban or warfarin from April 2011 to April 2013. Results. We identified 300 patients (147 on rivaroxaban versus 153 on warfarin). GI bleeding occurred in 4.8% patients with rivaroxaban when compared to 9.8% patients in warfarin group (p = 0.094). GI bleeding occurred in 8% with therapeutic doses of rivaroxaban (>10 mg/d) compared to 9.8% with warfarin (p = 0.65). Multivariate analysis showed that patients who were on rivaroxaban for <=40 days had a higher incidence of GI bleeding than those who were on it for >40 days (OR = 2.8, p = 0.023). Concomitant use of dual antiplatelet agents was associated with increased risk of GI bleeding in the rivaroxaban group (OR = 7.4, p = 0.0378). Prior GI bleeding was also a risk factor for GI bleeding in rivaroxaban group (OR = 15.5). Conclusion. The incidence of GI bleeding was similar between rivaroxaban and warfarin. The risk factors for GI bleeding with rivaroxaban were the first 40 days of taking the drug, concomitant dual antiplatelet agents, and prior GI bleeding. PMID- 26880902 TI - Clinical Experience with the PillCam Patency Capsule prior to Video Capsule Endoscopy: A Real-World Experience. AB - Background. In patients with known or suspected risk factors for gastrointestinal stenosis, the PillCam patency capsule (PC) is given before a video capsule endoscopy (VCE) in order to minimize the risk of capsule retention (CR). CR is considered unlikely upon excretion of the PC within 30 hours, excretion in an undamaged state after 30 hours, or radiological projection to the colon. Methods. We performed a retrospective analysis of 38 patients with risk factors for CR, who received a PC from 02/2013 to 04/2015 at Klinikum Augsburg. Results. Sixteen of our 38 patients observed a natural excretion after a mean time of 34 hours past ingestion. However, only 8 patients observed excretion within 30 hours, as recommended by the company. In 20 patients passage of the PC into the colon was shown via RFID-scan or radiological imaging (after 33 and 45 hours, resp.). Only 2 patients showed a pathologic PC result. In consequence, 32 patients received the VCE; no CR was observed. Conclusion. Our data indicates that a VCE could safely be performed even if the PC excretion time is longer than 30 hours and the excreted PC was not screened for damage. PMID- 26880903 TI - Gastrointestinal Symptoms of Patients with Fabry Disease. AB - In order to characterize gastrointestinal (GI) symptoms of 50 patients with Fabry disease (FD) (22 M; age range: 4-70 y; 35 adults and 15 children), validated questionnaires of GI symptoms were used to diagnose the functional gastrointestinal disorders (FGIDs) of the patients with GI symptoms (33/50 (66%); 25/35 adults and 8/15 children) according to Rome III criteria. In 16/25 of these adults and 2/8 of these children, the symptoms mimicked FGID. The adult subgroup included patients with unspecified functional bowel disorder (n = 9), functional bloating (n = 7), and IBS (n = 5), and the child subgroup included patients with abdominal migraine (n = 1) and IBS (n = 1). Among the 25 adults, 14 reported feeling full after a regular-size meal, and 12 complained of abdominal bloating/distension. All of the children with GI symptoms complained of low abdominal pain associated with changes in the form of the stool/improvements with defecation. In conclusion, according to Rome III criteria, the most frequent diagnoses of FGID among the adults with FD were unspecified functional bowel disorder, followed by functional bloating and IBS. The most frequent GI symptom in the children in our population was IBS-like abdominal pain, while the adults exhibited a full feeling following a regular-size meal and abdominal bloating/distension. PMID- 26880904 TI - Capsule Endoscopy for Ileitis with Potential Involvement of Other Sections of the Small Bowel. AB - Ileitis is defined as inflammation of the ileum. This condition includes ulcers, aphthous ulcers, erosions, and nodular or erythematous mucosa. Various etiologies are associated with ileitis. Crohn's disease, ulcerative colitis, medications such as nonsteroidal anti-inflammatory drugs, infectious conditions, neoplasms, infiltrative disorders, vasculitides, spondyloarthritis, endometriosis, and radiation therapy-related conditions involve the ileum. However, the differential diagnosis of terminal ileitis can be difficult in many cases. Video capsule endoscopy (VCE) has become a useful tool for the diagnosis of a variety of small bowel lesions. This review describes each of the various conditions associated with ileitis and the diagnostic value of VCE for ileitis, which may help identify and evaluate these conditions in clinical practice. Based on the information provided by VCE, a definitive diagnosis could be made using the patients' medical history, clinical course, laboratory and ileocolonoscopic findings, radiologic imaging findings, and histologic findings. PMID- 26880905 TI - Crude Aloe vera Gel Shows Antioxidant Propensities and Inhibits Pancreatic Lipase and Glucose Movement In Vitro. AB - Aloe vera gel (AVG) is traditionally used in the management of diabetes, obesity, and infectious diseases. The present study aimed to investigate the inhibitory potential of AVG against alpha-amylase, alpha-glucosidase, and pancreatic lipase activity in vitro. Enzyme kinetic studies using Michaelis-Menten (K m ) and Lineweaver-Burk equations were used to establish the type of inhibition. The antioxidant capacity of AVG was evaluated for its ferric reducing power, 2 diphenyl-2-picrylhydrazyl hydrate scavenging ability, nitric oxide scavenging power, and xanthine oxidase inhibitory activity. The glucose entrapment ability, antimicrobial activity, and total phenolic, flavonoid, tannin, and anthocyanin content were also determined. AVG showed a significantly higher percentage inhibition (85.56 +/- 0.91) of pancreatic lipase compared to Orlistat. AVG was found to increase the Michaelis-Menten constant and decreased the maximal velocity (V max) of lipase, indicating mixed inhibition. AVG considerably inhibits glucose movement across dialysis tubes and was comparable to Arabic gum. AVG was ineffective against the tested microorganisms. Total phenolic and flavonoid contents were 66.06 +/- 1.14 (GAE)/mg and 60.95 +/- 0.97 (RE)/mg, respectively. AVG also showed interesting antioxidant properties. The biological activity observed in this study tends to validate some of the traditional claims of AVG as a functional food. PMID- 26880906 TI - Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats. AB - Background. The incidence of metabolic syndrome co-existing with diabetes mellitus is on the rise globally. Objective. The present study was designed to develop a unique animal model that will mimic the pathological features seen in individuals with diabetes and metabolic syndrome, suitable for pharmacological screening of drugs. Materials and Methods. A combination of High-Fat Diet (HFD) and low dose of streptozotocin (STZ) at 30, 35, and 40 mg/kg was used to induce metabolic syndrome in the setting of diabetes mellitus in Wistar rats. Results. The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for the study to induce diabetes mellitus. Various components of metabolic syndrome such as dyslipidemia {(increased triglyceride, total cholesterol, LDL cholesterol, and decreased HDL cholesterol)}, diabetes mellitus (blood glucose, HbA1c, serum insulin, and C-peptide), and hypertension {systolic blood pressure} were mimicked in the developed model of metabolic syndrome co-existing with diabetes mellitus. In addition to significant cardiac injury, atherogenic index, inflammation (hs-CRP), decline in hepatic and renal function were observed in the HF-DC group when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis, and inflammation in heart, pancreas, liver, and kidney of HF-DC group as compared to NC. Conclusion. The present study has developed a unique rodent model of metabolic syndrome, with diabetes as an essential component. PMID- 26880907 TI - Subjective Memory Complaint and Depressive Symptoms among Older Adults in Portugal. AB - Background. Older adults report subjective memory complaints (SMCs) but whether these are related to depression remains controversial. In this study we investigated the relationship between the SMCs and depression and their predictors in a sample of old adults. Methods. This cross-sectional study enrolled 620 participants aged 55 to 96 years (74.04 +/- 10.41). Outcome measures included a sociodemographic and clinical questionnaire, a SMC scale (QSM), a Geriatric Depression Scale (GDS), a Mini-Mental Status Examination (MMSE), and a Montreal Cognitive Assessment (MoCA). Results. The QSM mean total score for the main results suggests that SMCs are higher in old adults with depressed symptoms, comparatively to nondepressed old adults. The GDS scores were positively associated with QSM but negatively associated with education, MMSE, and MoCA. GDS scores predicted almost 63.4% of variance. Scores on QSM and MoCA are significantly predicted by depression symptomatology. Conclusion. Depression symptoms, lower education level, and older age may be crucial to the comprehension of SMCs. The present study suggested that depression might play a role in the SMCs of the older adults and its treatment should be considered. PMID- 26880908 TI - Bacteriospermia and Its Impact on Basic Semen Parameters among Infertile Men. AB - Introduction. Semen analysis is considered as the surrogate marker for male fecundity while assessing infertile men. There are several reasons for altered semen quality and bacteriospermia could be one among them. Thereby the aim of our work is to study the semen culture and its impact on semen parameters among infertile men. Materials and Methods. Semen samples were collected from men attending infertility clinic. Semen parameters were analysed based on WHO guidelines. Also, samples were subjected to culture using standard bacteriological techniques. Results. A total of 85 samples were collected. A number of 47 (55.30%) had normal sperm count, 37 (43.50%) had oligozoospermia, and one (1.17%) had azoospermia. Teratozoospermia was the most common abnormality observed (81.17%) followed by asthenozoospermia (28.23%). The prevalence of bacteriospermia was 35.3%. Enterococcus faecalis (30%) was the most common organism isolated followed by Coagulase negative Staphylococcus (23.33%), Staphylococcus aureus (20%), and E. coli (10%). Other less frequently isolated organisms were Klebsiella pneumoniae (6.66%), Proteus sp. (6.66%), and Citrobacter sp. (3.33%). Conclusion. The presence of asymptomatic bacteriospermia did not correlate with abnormal semen parameters. PMID- 26880909 TI - Circulating Interferon-Gamma Levels Are Associated with Low Body Weight in Newly Diagnosed Kenyan Non-Substance Using Tuberculosis Individuals. AB - Although interferon-gamma, interleukin-10, and adiponectin are key immunopathogenesis mediators of tuberculosis, their association with clinical manifestations of early stage disease is inconclusive. We determined interferon gamma, interleukin-10, and adiponectin levels in clinically and phenotypically well-characterised non-substance using new pulmonary tuberculosis patients (n = 13) and controls (n = 14) from Kenya. Interferon-gamma levels (P < 0.0001) and interferon-gamma to interleukin-10 (P < 0.001) and interferon-gamma to adiponectin (P = 0.027) ratios were elevated in tuberculosis cases. Correlation analyses in tuberculosis cases showed associations of interferon-gamma levels with body weight (rho = -0.849; P < 0.0001), body mass index (rho = 0.664; P = 0.013), hip girth (rho = -0.579; P = 0.038), and plateletcrit (rho = 0.605; P = 0.028); interferon-gamma to interleukin-10 ratio with diastolic pressure (rho = 0.729; P = 0.005); and interferon-gamma to adiponectin ratio with body weight (rho = -0.560; P = 0.047), body mass index (rho = -0.604; P = 0.029), and plateletcrit (rho = 0.793; P = 0.001). Taken together, our results suggest mild inflammation in early stage infection characterised by upregulation of circulating interferon-gamma production in newly infected TB patients. PMID- 26880910 TI - FN-Identify: Novel Restriction Enzymes-Based Method for Bacterial Identification in Absence of Genome Sequencing. AB - Sequencing and restriction analysis of genes like 16S rRNA and HSP60 are intensively used for molecular identification in the microbial communities. With aid of the rapid progress in bioinformatics, genome sequencing became the method of choice for bacterial identification. However, the genome sequencing technology is still out of reach in the developing countries. In this paper, we propose FN Identify, a sequencing-free method for bacterial identification. FN-Identify exploits the gene sequences data available in GenBank and other databases and the two algorithms that we developed, CreateScheme and GeneIdentify, to create a restriction enzyme-based identification scheme. FN-Identify was tested using three different and diverse bacterial populations (members of Lactobacillus, Pseudomonas, and Mycobacterium groups) in an in silico analysis using restriction enzymes and sequences of 16S rRNA gene. The analysis of the restriction maps of the members of three groups using the fragment numbers information only or along with fragments sizes successfully identified all of the members of the three groups using a minimum of four and maximum of eight restriction enzymes. Our results demonstrate the utility and accuracy of FN-Identify method and its two algorithms as an alternative method that uses the standard microbiology laboratories techniques when the genome sequencing is not available. PMID- 26880911 TI - In Silico Phylogenetic Analysis and Molecular Modelling Study of 2-Haloalkanoic Acid Dehalogenase Enzymes from Bacterial and Fungal Origin. AB - 2-Haloalkanoic acid dehalogenase enzymes have broad range of applications, starting from bioremediation to chemical synthesis of useful compounds that are widely distributed in fungi and bacteria. In the present study, a total of 81 full-length protein sequences of 2-haloalkanoic acid dehalogenase from bacteria and fungi were retrieved from NCBI database. Sequence analysis such as multiple sequence alignment (MSA), conserved motif identification, computation of amino acid composition, and phylogenetic tree construction were performed on these primary sequences. From MSA analysis, it was observed that the sequences share conserved lysine (K) and aspartate (D) residues in them. Also, phylogenetic tree indicated a subcluster comprised of both fungal and bacterial species. Due to nonavailability of experimental 3D structure for fungal 2-haloalkanoic acid dehalogenase in the PDB, molecular modelling study was performed for both fungal and bacterial sources of enzymes present in the subcluster. Further structural analysis revealed a common evolutionary topology shared between both fungal and bacterial enzymes. Studies on the buried amino acids showed highly conserved Leu and Ser in the core, despite variation in their amino acid percentage. Additionally, a surface exposed tryptophan was conserved in all of these selected models. PMID- 26880912 TI - Effect of Metformin and Sitagliptin on Doxorubicin-Induced Cardiotoxicity in Rats: Impact of Oxidative Stress, Inflammation, and Apoptosis. AB - Doxorubicin (DOX) is a widely used antineoplastic drug whose efficacy is limited by its cardiotoxicity. The aim of this study was to investigate the possible protective role of the antidiabetic drugs metformin (250 mg/kg dissolved in DW p.o. for seven days) and sitagliptin (10 mg/kg dissolved in DW p.o. for seven days) in a model of DOX-induced (single dose 15 mg/kg i.p. at the fifth day) cardiotoxicity in rats. Results of our study revealed that pretreatment with metformin or sitagliptin produced significant (P < 0.05) cardiac protection manifested by a significant decrease in serum levels of LDH and CK-MB enzymes and cardiac MDA and total nitrites and nitrates levels, a significant increase in cardiac SOD activity, and remarkable improvement in the histopathological features as well as a significant reduction in the immunohistochemical expression of COX-2, iNOS, and caspase-3 enzymes as compared to DOX group. These results may suggest using metformin and/or sitagliptin as preferable drugs for diabetic patients suffering from cancer and receiving DOX in their chemotherapy regimen. PMID- 26880913 TI - Chalcone Scaffold in Anticancer Armamentarium: A Molecular Insight. AB - Cancer is an inevitable matter of concern in the medicinal chemistry era. Chalcone is the well exploited scaffold in the anticancer domain. The molecular mechanism of chalcone at cellular level was explored in past decades. This mini review provides the most recent updates on anticancer potential of chalcones. PMID- 26880914 TI - Hospital Admission Patterns in Children with CAH: Admission Rates and Adrenal Crises Decline with Age. AB - Objective. To examine patterns of hospitalisation for acute medical conditions in children with congenital adrenal hyperplasia (CAH). Design. A retrospective study of hospitalisation using administrative data. Setting. All hospitals in NSW, Australia. Patients. All patients admitted with CAH and a random sample of admissions in patients aged 0 to 18 years without adrenal insufficiency (AI). Main Outcome Measures. Admissions and comorbidities by age and sex. Results. Of 573 admissions for medical problems in CAH children, 286 (49.9%) were in males, and 236 (41.2%) had a principal diagnosis of CAH or had an adrenal crisis (AC). 37 (6.5%) ACs were recorded. An infection was found in 43.5% (n = 249) of the CAH patient admissions and 51.7% (n = 1613) of the non-AI group, p < 0.001. Children aged up to one year had the highest number of admissions (n = 149) and six ACs (four in males). There were 21 ACs recorded for children aged 1-5 years. Older CAH children had fewer admissions and fewer ACs. No in-hospital deaths were recorded. Conclusions. Admission for medical problems in CAH children declines with age. An AC was recorded in 6.5% of the admissions, with the majority of ACs occurring in the 1 to 5 years age group and there were no deaths. PMID- 26880915 TI - Pharmacogenetics of Risperidone and Cardiovascular Risk in Children and Adolescents. AB - Objective. To identify the frequency of obesity and metabolic complications in child and adolescent users of risperidone. Potential associations with clinical parameters and SNPs of the HTR2C, DRD2, LEP, LEPR, MC4R, and CYP2D6 genes were analyzed. Methods. Samples from 120 risperidone users (8-20 years old) were collected and SNPs were analyzed, alongside assessment of chronological and bone ages, prescribed and weight-adjusted doses, use of other psychotropic drugs, waist circumference, BMI z-scores, blood pressure, HOMA-IR index, fasting levels of serum glucose, insulin, cholesterol, triglycerides, transaminases, and leptin. Results. Thirty-two (26.7%) patients were overweight and 5 (4.2%) obese. Hypertension was recorded in 8 patients (6.7%), metabolic syndrome in 6 (5%), and increased waist circumference in 20 (16.7%). The HOMA-IR was high for 22 patients (18.3%), while total cholesterol and triglycerides were high in 20 (16.7%) and 41 (34.2%) patients, respectively. SNP associations were found for LEP, HTR2C, and CYP2D6 with BMI; CYP2D6 with blood pressure, ALT, and HOMA-IR; HTR2C and LEPR with leptin levels; MC4R and DRD2 with HOMA-IR; HTR2C with WC; and LEP with ALT. Conclusions. Although not higher than in the general pediatric population, a high frequency of patients was overweight/obese, with abnormalities in metabolic parameters and some pharmacogenetic associations. PMID- 26880916 TI - Determinants of Cervical Cancer Screening Uptake among Women in Ilorin, North Central Nigeria: A Community-Based Study. AB - Introduction. Cancer of the cervix is the leading cause of cancer deaths among women in developing countries. Screening is one of the most cost effective control strategies for the disease. This study assessed the determinants of cervical cancer screening uptake among Nigerian women. Methodology. This cross sectional study was conducted using multistage sampling technique among 338 participants in Ilorin, North Central Nigeria. A pretested questionnaire was used for data collection and data analysis was done using SPSS version 21. Chi-square test was used for bivariate analysis while binary logistic regression was used for multivariate analysis. Statistical significance was set at p < 0.05. Results. Only 8.0% of the respondents had ever been screened for cancer of the cervix. The proportion of women who had ever been screened was significantly higher among those who demonstrated positive attitude to screening (81.5%, p = 0.001), respondents who were aware of the disease (100.0%, p = 0.001), and those who were aware of cervical cancer screening (88.9%, p = 0.001). Respondents who had negative attitude had 63% lesser odds of being screened compared to those who had positive attitudes towards screening (AOR; 0.37, 95% CI; 0.01-0.28). Conclusion. There is urgent need to improve the knowledge base and attitude of Nigerian women to enhance cervical cancer screening uptake among them. PMID- 26880917 TI - What Prevents Men Aged 40-64 Years from Prostate Cancer Screening in Namibia? AB - Objectives. Although a growing body of evidence demonstrates the public health burden of prostate cancer in SSA, relatively little is known about the underlying factors surrounding the low levels of testing for the disease in the context of this region. Using Namibia Demographic Health Survey dataset (NDHS, 2013), we examined the factors that influence men's decision to screen for prostate cancer in Namibia. Methods. We use complementary log-log regression models to explore the determinants of screening for prostate cancer. We also corrected for the effect of unobserved heterogeneity that may affect screening behaviours at the cluster level. Results. The results show that health insurance coverage (OR = 2.95, p = 0.01) is an important predictor of screening for prostate cancer in Namibia. In addition, higher education and discussing reproductive issues with a health worker (OR = 2.02, p = 0.05) were more likely to screening for prostate cancer. Conclusions. A universal health insurance scheme may be necessary to increase uptake of prostate cancer screening. However it needs to be acknowledged that expanded screening can have negative consequences and any allocation of scarce resources towards screening must be guided by evidence obtained from the local context about the costs and benefits of screening. PMID- 26880918 TI - Expression of Factor X in BHK-21 Cells Promotes Low Pathogenic Influenza Viruses Replication. AB - A cDNA clone for factor 10 (FX) isolated from chicken embryo inserted into the mammalian cell expression vector pCDNA3.1 was transfected into the baby hamster kidney (BHK-21) cell line. The generated BHK-21 cells with inducible expression of FX were used to investigate the efficacy of the serine transmembrane protease to proteolytic activation of influenza virus hemagglutinin (HA) with monobasic cleavage site. Data showed that the BHK-21/FX stably expressed FX after ten serial passages. The cells could proteolytically cleave the HA of low pathogenic avian influenza virus at multiplicity of infection 0.01. Growth kinetics of the virus on BHK-21/FX, BHK-21, and MDCK cells were evaluated by titrations of virus particles in each culture supernatant. Efficient multicycle viral replication was markedly detected in the cell at subsequent passages. Virus titration demonstrated that BHK-21/FX cell supported high-titer growth of the virus in which the viral titer is comparable to the virus grown in BHK-21 or MDCK cells with TPCK-trypsin. The results indicate potential application for the BHK-21/FX in influenza virus replication procedure and related studies. PMID- 26880919 TI - Comparison of the Mechanical Properties of Early Leukocyte- and Platelet-Rich Fibrin versus PRGF/Endoret Membranes. AB - Objectives. The mechanical properties of membranes are important factors in the success of treatment and clinical handling. The goal of this study was to compare the mechanical properties of early leukocyte- and platelet-rich fibrin (L-PRF) versus PRGF/Endoret membrane. Materials and Methods. In this experimental study, membranes were obtained from 10 healthy male volunteers. After obtaining 20 cc venous blood from each volunteer, 10 cc was used to prepare early L-PRF (group 1) and the rest was used to get a membrane by PRGF-Endoret system (group 2). Tensile loads were applied to specimens using universal testing machine. Tensile strength, stiffness, and toughness of the two groups of membranes were calculated and compared by paired t-test. Results. The mean tensile strength and toughness were higher in group 1 with a significant difference (P < 0.05). The mean stiffness in group 1 was also higher but not statistically significant (P > 0.05). Conclusions. The results showed that early L-PRF membranes had stronger mechanical properties than membranes produced by PRGF-Endoret system. Early L-PRF membranes might have easier clinical handling and could be a more proper scaffold in periodontal regenerative procedures. The real results of the current L-PRF should be in fact much higher than what is reported here. PMID- 26880920 TI - Micellar Enhanced Spectrofluorimetric Method for the Determination of Ponatinib in Human Plasma and Urine via Cremophor RH 40 as Sensing Agent. AB - An impressively simple and precise spectrofluorimetric procedure was established and validated for ponatinib (PTB) quantitation in biological fluids such as human plasma and human urine. This method depends on examining the fluorescence characteristics of PTB in a micellar system of Cremophor RH 40 (Cr RH 40). Cr RH 40 enhanced the intrinsic fluorescence of PTB distinctly in aqueous water. The fluorescence spectra of PTB was recorded at 457 nm following its excitation at 305 nm. Maximum fluorescence intensity was attained by addition of 0.7 mL of Cr RH 40 and one mL of phosphate buffer to PTB aliquots and then dilution with distilled water. There is a linear relationship between the fluorescence intensity of PTB and its concentration over the range 5-120 ngmL(-1), with limit of detection and limit of quantification equal to 0.905 ngmL(-1) and 2.742 ngmL( 1), respectively. The accuracy and the precisions of the proposed method were checked and gave adequate results. The adopted method was applied with a great success for PTB quantitation in different biological matrices (spiked human plasma and urine) giving high recovery values. PMID- 26880921 TI - Enantioseparation of Citalopram by RP-HPLC, Using Sulfobutyl Ether-beta Cyclodextrin as a Chiral Mobile Phase Additive. AB - Enantiomeric separation of citalopram (CIT) was developed using a reversed phase HPLC (RP-HPLC) with sulfobutylether-beta-cyclodextrin (SBE-beta-CD) as a chiral mobile phase additive. The effects of the pH value of aqueous buffer, concentration of chiral additive, composition of mobile phase, and column temperature on the enantioseparation of CIT were investigated on the Hedera ODS-2 C18 column (250 mm * 4.6 mm * 5.0 um). A satisfactory resolution was achieved at 25 degrees C using a mobile phase consisting of a mixture of aqueous buffer (pH of 2.5, 5 mM sodium dihydrogen phosphate, and 12 mM SBE-beta-CD), methanol, and acetonitrile with a volumetric ratio of 21 : 3 : 1 and flow rate of 1.0 mL/min. This analytical method was evaluated by examining the precision (lower than 3.0%), linearity (regression coefficients close to 1), limit of detection (0.070 ug/mL for (R)-CIT and 0.076 ug/mL for (S)-CIT), and limit of quantitation (0.235 ug/mL for (R)-CIT and 0.254 ug/mL for (S)-CIT). PMID- 26880922 TI - Integration of Rabbit Adipose Derived Mesenchymal Stem Cells to Hydroxyapatite Burr Hole Button Device for Bone Interface Regeneration. AB - Adipose Derived Mesenchymal Stem Cells, multipotent stem cells isolated from adipose tissue, present close resemblance to the natural in vivo milieu and microenvironment of bone tissue and hence widely used for in bone tissue engineering applications. The present study evaluates the compatibility of tissue engineered hydroxyapatite burr hole button device (HAP-BHB) seeded with Rabbit Adipose Derived Mesenchymal Stem Cells (ADMSCs). Cytotoxicity, oxidative stress response, apoptotic behavior, attachment, and adherence of adipose MSC seeded on the device were evaluated by scanning electron and confocal microscopy. The results of the MTT (3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide) assay indicated that powdered device material was noncytotoxic up to 0.5 g/mL on cultured cells. It was also observed that oxidative stress related reactive oxygen species production and apoptosis on cell seeded device were similar to those of control (cells alone) except in 3-day period which showed increased reactive oxygen species generation. Further scanning electron and confocal microscopy indicated a uniform attachment of cells and viability up to 200 MUm deep inside the device, respectively. Based on the results, it can be concluded that the in-house developed HAP-BHB device seeded with ADMSCs is nontoxic/safe compatible device for biomedical application and an attractive tissue engineered device for calvarial defect regeneration. PMID- 26880923 TI - Comparison of Bone Mineral Density in Thalassemia Major Patients with Healthy Controls. AB - Chronic hemoglobinopathies like thalassemia are associated with many osteopathies like osteoporosis. Methods. This observational study was carried out to compare the bone mineral density (BMD) in transfusion dependent thalassemics with that of healthy controls. Thirty-two thalassemia patients, aged 2-18 years, and 32 age and sex matched controls were studied. The bone mineral concentration (BMC) and BMD were assessed at lumbar spine, distal radius, and neck of femur. Biochemical parameters like serum calcium and vitamin D levels were also assessed. Results. The BMC of neck of femur was significantly low in cases in comparison to controls. We also observed significantly lower BMD at the lumbar spine in cases in comparison to controls. A significantly positive correlation was observed between serum calcium levels and BMD at neck of femur. Conclusion. Hence, low serum calcium may be used as a predictor of low BMD especially in populations where incidence of hypovitaminosis D is very high. PMID- 26880924 TI - Rapid Accumulation of Total Lipid in Rhizoclonium africanum Kutzing as Biodiesel Feedstock under Nutrient Limitations and the Associated Changes at Cellular Level. AB - Increase of total lipid and the proportion of the favorable fatty acids in marine green filamentous macroalga Rhizoclonium africanum (Chlorophyceae) was studied under nitrate and phosphate limitations. These stresses were given by both eliminating and doubling the required amounts of nitrate and phosphate salts in the growth media. A significant twofold increase in total lipid (193.03 mg/g) was achieved in cells in absence of nitrate in the culture medium, followed by phosphate limitation (142.65 mg/g). The intracellular accumulation of neutral lipids was observed by fluorescence microscopy. The scanning electron microscopic study showed the major structural changes under nutrient starvation. Fourier transform infrared spectroscopy (FTIR) revealed the presence of ester (C-O-C stretching), ketone (C-C stretching), carboxylic acid (O-H bending), phosphine (P H stretching), aromatic (C-H stretching and bending), and alcohol (O-H stretching and bending) groups in the treated cells indicating the high accumulation of lipid hydrocarbons in the treated cells. Elevated levels of fatty acids favorable for biodiesel production, that is, C16:0, C16:1, C18:1, and C20:1, were identified under nitrate- and phosphate-deficient conditions. This study shows that the manipulation of cultural conditions could affect the biosynthetic pathways leading to increased lipid production while increasing the proportion of fatty acids suitable for biodiesel production. PMID- 26880925 TI - Spectrum and the In Vitro Antifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis. AB - Background. In Ethiopia, little is known regarding the distribution and the in vitro antifungal susceptibility profile of yeasts. Objective. This study was undertaken to determine the spectrum and the in vitro antifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC. Method. Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method. Result. One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART. C. albicans was the most frequently isolated species followed by C. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorula species. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively. Conclusion. Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs. PMID- 26880926 TI - Modulation of mecA Gene Expression by Essential Oil from Salvia sclarea and Synergism with Oxacillin in Methicillin Resistant Staphylococcus epidermidis Carrying Different Types of Staphylococcal Chromosomal Cassette mec. AB - The essential oil (EO) from Salvia sclarea was shown to increase the susceptibility of methicillin resistant Staphylococcus epidermidis (MRSE) isolates to oxacillin. The purpose of this study was to investigate the effect of EO from S. sclarea on expression of mecA gene of MRSE carrying different types of staphylococcal chromosomal cassette (SCCmec) and to evaluate potential synergistic effect of EO with oxacillin. Using real-time PCR we found that EO alone inhibited the expression of the resistant genes mecA, mecR1, and mecI and blaZ, blaR1, and blaI. The use of the combination of EO with oxacillin resulted in significantly inhibited expression of mecA gene in all tested strains with different types of SCCmec. Using time-kill assay and checkerboard assay we confirmed synergistic effect of EO from S. sclarea and oxacillin in MRSE. PMID- 26880927 TI - In Vitro Antimicrobial Activity of Spices and Medicinal Herbs against Selected Microbes Associated with Juices. AB - In the present investigation, comparison of antimicrobial activities of different spices, Curcuma longa, Zingiber officinale, and Mentha arvensis, and medicinal herbs, such as Withania somnifera, Rauvolfia serpentina, Emblica officinalis, Terminalia arjuna, and Centella asiatica, was evaluated. Different extraction solvents (acetone, methanol, ethanol, and water) were used and extracts were examined against Bacillus cereus, Serratia sp., Rhodotorula mucilaginosa, Aspergillus flavus, and Penicillium citrinum isolated from juices. Extracts from the medicinal herb and spices have significant activity. B. cereus was the most sensitive and R. mucilaginosa was the most resistant among the microorganisms tested. Ethanolic and methanolic extract of C. asiatica displayed maximum diameter of inhibition zone against bacteria and yeast and percentage mycelial inhibition against moulds. This study confirmed the potential of selected extracts of spices as effective natural food preservative in juices. PMID- 26880928 TI - In Vitro Antimicrobial Activity of Essential Oil of Thymus schimperi, Matricaria chamomilla, Eucalyptus globulus, and Rosmarinus officinalis. AB - In this study, the in vitro antimicrobial activities of four plant essential oils (T. schimperi, E. globulus, R. officinalis, and M. Chamomilla) were evaluated against bacteria and fungi. The studies were carried out using agar diffusion method for screening the most effective essential oils and agar dilution to determine minimum inhibitory concentration of the essential oils. Results of this study revealed that essential oils of T. schimperi, E. globulus, and R. officinalis were active against bacteria and some fungi. The antimicrobial effect of M. chamomilla was found to be weaker and did not show any antimicrobial activity. The minimum inhibitory concentration values of T. schimperi were <15.75 mg/mL for most of the bacteria and fungi used in this study. The minimum inhibitory concentration values of the other essential oils were in the range of 15.75-36.33 mg/mL against tested bacteria. This study highlighted the antimicrobial activity of the essential oil of E. globulus, M. chamomilla, T. Schimperi, and R. officinalis. The results indicated that T. schimperi have shown strong antimicrobial activity which could be potential candidates for preparation of antimicrobial drug preparation. PMID- 26880929 TI - Erythema Ab Igne due to Heating Pad Use: A Case Report and Review of Clinical Presentation, Prevention, and Complications. AB - Erythema ab igne is an asymptomatic cutaneous condition caused by exposure to heat. Cases of erythema ab igne may prove to be diagnostically challenging due to lack of familiarity with the condition. While this dermatosis carries a favorable prognosis, nonmelanoma skin cancers have been reported to arise within lesions of erythema ab igne. Erythema ab igne is preventable, and, thus, clinicians should provide education regarding safe use of heating devices to patients using these products in both outpatient and inpatient settings. PMID- 26880930 TI - Pica for Uncooked Basmati Rice in Two Women with Iron Deficiency and a Review of Ryzophagia. AB - Reports of pica for uncooked rice (ryzophagia) in adults who reside in European and derivative countries are uncommon. We evaluated and treated two nonpregnant women with pica for uncooked basmati rice. Both women reported fatigue, abdominal discomfort after consuming large quantities of uncooked basmati rice, and hair loss. One woman was from India and the other was from Pakistan. Both women were vegetarians. Basmati was the local rice in their native countries and their usual rice in the USA. Both women had tooth damage due to eating uncooked rice and iron deficiency with microcytic anemia attributed to menorrhagia and multiparity. Ryzophagia and other manifestations (except tooth damage) resolved after iron dextran therapy. We review and discuss other reports of ryzophagia associated with iron deficiency, pregnancy, race/ethnicity, geographic origin, and local traditions. We conclude that adults with ryzophagia in European and derivative countries are likely to be non-Europeans. PMID- 26880931 TI - Successful Treatment of Secondary Aortoenteric Fistula with a Special Graft. AB - Aortoenteric fistula is an uncommon but life-threatening cause of gastrointestinal blood loss. We report a case of a 70-year-old man who presented to the emergency department with an episode of melena and infection in the left inguinal region. Diagnosis of secondary aortoenteric fistula was made between the left limb of the aortobifemoral graft and the descending colon. We performed excision of the infected graft and in situ silver acetate coating of prosthetic vascular graft replacement (aortoleft femoral) on the patient. This study reports a rare type of secondary aortoenteric fistula to the left colon, and it describes an unusual and successful surgical treatment. Antimicrobial coating of prosthetic vascular grafts may be a good alternative in the presence of graft infection associated with aortoenteric fistula because in situ grafts may carry an increased risk of reinfection. PMID- 26880932 TI - Longitudinal Cell Tracking and Simultaneous Monitoring of Tissue Regeneration after Cell Treatment of Natural Tendon Disease by Low-Field Magnetic Resonance Imaging. AB - Treatment of tendon disease with multipotent mesenchymal stromal cells (MSC) is a promising option to improve tissue regeneration. To elucidate the mechanisms by which MSC support regeneration, longitudinal tracking of MSC labelled with superparamagnetic iron oxide (SPIO) by magnetic resonance imaging (MRI) could provide important insight. Nine equine patients suffering from tendon disease were treated with SPIO-labelled or nonlabelled allogeneic umbilical cord-derived MSC by local injection. Labelling of MSC was confirmed by microscopy and MRI. All animals were subjected to clinical, ultrasonographical, and low-field MRI examinations before and directly after MSC application as well as 2, 4, and 8 weeks after MSC application. Hypointense artefacts with characteristically low signal intensity were identified at the site of injection of SPIO-MSC in T1- and T2 (*) -weighted gradient echo MRI sequences. They were visible in all 7 cases treated with SPIO-MSC directly after injection, but not in the control cases treated with nonlabelled MSC. Furthermore, hypointense artefacts remained traceable within the damaged tendon tissue during the whole follow-up period in 5 out of 7 cases. Tendon healing could be monitored at the same time. Clinical and ultrasonographical findings as well as T2-weighted MRI series indicated a gradual improvement of tendon function and structure. PMID- 26880933 TI - Proangiogenic Features of Mesenchymal Stem Cells and Their Therapeutic Applications. AB - Mesenchymal stem cells (MSCs) have shown their therapeutic potency for treatment of cardiovascular diseases owing to their low immunogenicity, ease of isolation and expansion, and multipotency. As multipotent progenitors, MSCs have revealed their ability to differentiate into various cell types and could promote endogenous angiogenesis via microenvironmental modulation. Studies on cardiovascular diseases have demonstrated that transplanted MSCs could engraft at the injured sites and differentiate into cardiomyocytes and endothelial cells as well. Accordingly, several clinical trials using MSCs have been performed and revealed that MSCs may improve relevant clinical parameters in patients with vascular diseases. To fully comprehend the characteristics of MSCs, understanding their intrinsic property and associated modulations in tuning their behaviors as well as functions is indispensable for future clinical translation of MSC therapy. This review will focus on recent progresses on endothelial differentiation and potential clinical application of MSCs, with emphasis on therapeutic angiogenesis for treatment of cardiovascular diseases. PMID- 26880935 TI - Cancer Stem Cell Signaling during Repopulation in Head and Neck Cancer. AB - The aim of the study was to investigate cancer stem signaling during the repopulation response of a head and neck squamous cell cancer (HNSCC) xenograft after radiation treatment. Xenografts were generated from low passage HNSCC cells and were treated with either sham radiation or 15 Gy in one fraction. At different time points, days 0, 3, and 10 for controls and days 4, 7, 12, and 21, after irradiation, 3 tumors per group were harvested for global gene expression, pathway analysis, and immunohistochemical evaluation. 316 genes were identified that were associated with a series of stem cell-related genes and were differentially expressed (p <= 0.01 and 1.5-fold) at a minimum of one time point in UT-SCC-14 xenografts after radiation. The largest network of genes that showed significant changes after irradiation was associated with CD44, NOTCH1, and MET. c-MET and ALDH1A3 staining correlated with the changes in gene expression. A clear pattern emerged that was consistent with the growth inhibition data in that genes associated with stem cell pathways were most active at day 7 and day 12 after irradiation. The MET/CD44 axis seemed to be an important component of the repopulation response. PMID- 26880934 TI - Mimicking Neural Stem Cell Niche by Biocompatible Substrates. AB - Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to building in vitro models that include the relevant components of the in vivo niche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for the in vitro and in vivo mimicking of extracellular NSCs conditions. PMID- 26880937 TI - Osteogenesis from Dental Pulp Derived Stem Cells: A Novel Conditioned Medium Including Melatonin within a Mixture of Hyaluronic, Butyric, and Retinoic Acids. AB - Human dental pulp stem cells (hDPSCs) have shown relevant potential for cell therapy in the orthopedic and odontoiatric fields. The optimization of their osteogenic potential is currently a major challenge. Vascular endothelial growth factor A (VEGF A) has been recently reported to act as a major conductor of osteogenesis in vitro and in vivo. Here, we attempted to prime endogenous VEGF A expression without the need for viral vector mediated gene transfer technologies. We show that hDPSCs exposure to a mixture of hyaluronic, butyric, and retinoic acids (HA + BU + RA) induced the transcription of a gene program of osteogenesis and the acquirement of an osteogenic lineage. Such response was also elicited by cell exposure to melatonin, a pleiotropic agent that recently emerged as a remarkable osteogenic inducer. Interestingly, the commitment to the osteogenic fate was synergistically enhanced by the combinatorial exposure to a conditioned medium containing both melatonin and HA + BU + RA. These in vitro results suggest that in vivo osteogenesis might be improved and further studies are needed. PMID- 26880936 TI - Vascular Wall-Resident Multipotent Stem Cells of Mesenchymal Nature within the Process of Vascular Remodeling: Cellular Basis, Clinical Relevance, and Implications for Stem Cell Therapy. AB - Until some years ago, the bone marrow and the endothelial cell compartment lining the vessel lumen (subendothelial space) were thought to be the only sources providing vascular progenitor cells. Now, the vessel wall, in particular, the vascular adventitia, has been established as a niche for different types of stem and progenitor cells with the capacity to differentiate into both vascular and nonvascular cells. Herein, vascular wall-resident multipotent stem cells of mesenchymal nature (VW-MPSCs) have gained importance because of their large range of differentiation in combination with their distribution throughout the postnatal organism which is related to their existence in the adventitial niche, respectively. In general, mesenchymal stem cells, also designated as mesenchymal stromal cells (MSCs), contribute to the maintenance of organ integrity by their ability to replace defunct cells or secrete cytokines locally and thus support repair and healing processes of the affected tissues. This review will focus on the central role of VW-MPSCs within vascular reconstructing processes (vascular remodeling) which are absolute prerequisite to preserve the sensitive relationship between resilience and stability of the vessel wall. Further, a particular advantage for the therapeutic application of VW-MPSCs for improving vascular function or preventing vascular damage will be discussed. PMID- 26880939 TI - Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells. AB - Background. Systemic sclerosis (SSc) is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia) and opening (microstomia). We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs) injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS). Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO). In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS) performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials. PMID- 26880938 TI - Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration. AB - The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair. PMID- 26880940 TI - High Content Analysis of Human Pluripotent Stem Cell Derived Hepatocytes Reveals Drug Induced Steatosis and Phospholipidosis. AB - Hepatotoxicity is one of the most cited reasons for withdrawal of approved drugs from the market. The use of nonclinically relevant in vitro and in vivo testing systems contributes to the high attrition rates. Recent advances in differentiating human induced pluripotent stem cells (hiPSCs) into pure cultures of hepatocyte-like cells expressing functional drug metabolizing enzymes open up possibilities for novel, more relevant human cell based toxicity models. The present study aimed to investigate the use of hiPSC derived hepatocytes for conducting mechanistic toxicity testing by image based high content analysis (HCA). The hiPSC derived hepatocytes were exposed to drugs known to cause hepatotoxicity through steatosis and phospholipidosis, measuring several endpoints representing different mechanisms involved in drug induced hepatotoxicity. The hiPSC derived hepatocytes were benchmarked to the HepG2 cell line and generated robust HCA data with low imprecision between plates and batches. The different parameters measured were detected at subcytotoxic concentrations and the order of which the compounds were categorized (as severe, moderate, mild, or nontoxic) based on the degree of injury at isomolar concentration corresponded to previously published data. Taken together, the present study shows how hiPSC derived hepatocytes can be used as a platform for screening drug induced hepatotoxicity by HCA. PMID- 26880942 TI - Endothelial Progenitor Cell Migration-Enhancing Factors in the Secretome of Placental-Derived Mesenchymal Stem Cells. AB - Therapeutic potentials of mesenchymal stem cells (MSCs) depend largely on their ability to secrete cytokines or factors that modulate immune response, enhance cell survival, and induce neovascularization in the target tissues. We studied the secretome profile of gestational tissue-derived MSCs and their effects on functions of endothelial progenitor cells (EPCs), another angiogenic cell type that plays an important role during the neovascularization. MSCs derived from placental tissues (PL-MSCs) significantly enhanced EPC migration while BM-MSCs, which are the standard source of MSCs for various clinical applications, did not. By using protein fractionation and mass spectrometry analysis, we identified several novel candidates for EPC migration enhancing factor in PL-MSCs secretome that could be used to enhance neovascularization in the injured/ischemic tissues. We recommend that the strategy developed in our study could be used to systematically identify therapeutically useful molecules in the secretomes of other MSC sources for the clinical applications. PMID- 26880941 TI - A Role for Notch Signalling in Breast Cancer and Endocrine Resistance. AB - Over the past decade, there has been growing interest in the Notch signalling pathway within the breast cancer field. This interest stemmed initially from the observation that Notch signalling is aberrantly activated in breast cancer and its effects on various cellular processes including proliferation, apoptosis, and cancer stem cell activity. However more recently, elevated Notch signalling has been correlated with therapy resistance in oestrogen receptor-positive breast cancer. As a result, inhibiting Notch signalling with therapeutic agents is being explored as a promising treatment option for breast cancer patients. PMID- 26880943 TI - The New Role of CD163 in the Differentiation of Bone Marrow Stromal Cells into Vascular Endothelial-Like Cells. AB - Bone marrow stromal cells (BMSCs) can differentiate into vascular endothelial cells (VECs). It is regarded as an important solution to cure many diseases, such as ischemic diseases and diabetes. However, the mechanisms underlying BMSC differentiation into VECs are not well understood. Recent reports showed that CD163 expression was associated with angiogenesis. In this study, overexpression of CD163 in BMSCs elevated the protein level of the endothelial-associated markers CD31, Flk-1, eNOS, and VE-cadherin, significantly increased the proportion of Alexa Fluor 488-acetylated-LDL-positive VECs, and promoted angiogenesis on Matrigel. Furthermore, we demonstrated that CD163 acted downstream homeobox containing 1 (Hmbox1) and upstream fibroblast growth factor 2 (FGF-2). These data suggested that CD163 was involved in Hmbox1/CD163/FGF-2 signal pathway in BMSC differentiation into vascular endothelial-like cells. We found a new signal pathway and a novel target for further investigating the gene control of BMSC differentiation into a VEC lineage. PMID- 26880944 TI - The Use of Human Adipose-Derived Stem Cells in the Treatment of Physiological and Pathological Vulvar Dystrophies. AB - "Vulvar dystrophy" is characterized by chronic alterations of vulvar trophism, occurring in both physiological (menopause) and pathological (lichen sclerosus, vulvar graft-versus-host disease) conditions. Associated symptoms are itching, burning, dyspareunia and vaginal dryness. Current treatments often do not imply a complete remission of symptoms. Adipose-Derived Stem Cells (ADSCs) injection represents a valid alternative therapy to enhance trophism and tone of dystrophic tissues. We evaluated efficacy of ADSCs-based therapy in the dystrophic areas. From February to April 2013 we enrolled 8 patients with vulvar dystrophy. A biopsy specimen was performed before and after treatment. Digital photographs were taken at baseline and during the follow-up. Pain was detected with Visual Analogue Scale and sexual function was evaluated with Female Sexual Function Index. All patients received 2 treatments in 3 months. Follow-up was at 1 week , 1 and 3 months, and 1 and 2 years. We obtained a significant vulvar trophism enhancement in all patients, who reported pain reduction and sexual function improvement. Objective exam with speculum was easy to perform after treatment. We believe ADSCs-based therapy finds its application in the treatment of vulvar dystrophies, since ADSCs could induce increased vascularization due to their angiogenic properties and tissue trophism improvement thanks to their eutrophic effect. PMID- 26880945 TI - Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children. AB - Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT. PMID- 26880946 TI - LncRNAs in Stem Cells. AB - Noncoding RNAs are critical regulatory factors in essentially all forms of life. Stem cells occupy a special position in cell biology and Biomedicine, and emerging results show that multiple ncRNAs play essential roles in stem cells. We discuss some of the known ncRNAs in stem cells such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, adult stem cells, and cancer stem cells with a focus on long ncRNAs. Roles and functional mechanisms of these lncRNAs are summarized, and insights into current and future studies are presented. PMID- 26880947 TI - MicroRNAs-Proteomic Networks Characterizing Human Medulloblastoma-SLCs. AB - Medulloblastoma (MB) is the most common malignant brain tumor of pediatric age and is characterized by cells expressing stem, astroglial, and neuronal markers. Among them, stem-like cells (hMB-SLCs) represent a fraction of the tumor cell population with the potential of self-renewal and proliferation and have been associated with tumor poor prognosis. In this context, microRNAs have been described as playing a pivotal role in stem cells differentiation. In our paper, we analyze microRNAs profile and genes expression of hMB-SLCs before and after Retinoic Acid- (RA-) induced differentiation. We aimed to identify pivotal players of specific pathways sustaining stemness and/or tumor development and progression and integrate the results of our recent proteomic study. Our results uncovered 22 differentially expressed microRNAs that were used as input together with deregulated genes and proteins in the Genomatix Pathway System (GePS) analysis revealing 3 subnetworks that could be interestingly involved in the maintenance of hMB-SLCs proliferation. Taken together, our findings highlight microRNAs, genes, and proteins that are significantly modulated in hMB-SLCs with respect to their RA-differentiated counterparts and could open new perspectives for prognostic and therapeutic intervention on MB. PMID- 26880948 TI - Induced Pluripotent Stem Cells and Outer Retinal Disease. AB - The retina, which is composed of multiple layers of differing cell types, has been considered the first choice for gene therapy, disease modeling, and stem cell-derived retinal cell transplant therapy. Because of its special characteristics, the retina, located in the posterior part of the eye, can be well observed directly after gene therapy or transplantation. The blood-retinal barrier is part of a specialized ocular microenvironment that is immune privileged. This protects transplanted cells and tissue. Having two eyes makes perfect natural control possible after a single eye receives gene or stem cell therapy. For this reason, research about exploring retinal diseases' underlying molecular mechanisms and potential therapeutic approach using stem cell technique has been developing rapidly. This review is to present an up-to-date summary of the iPSC's sources, variations, differentiation methods, and the wide-ranging application of iPSCs-RPCS or iPSCs-RPE on retinal disease modeling, diagnostics, and therapeutics. PMID- 26880949 TI - The Interaction between Adult Cardiac Fibroblasts and Embryonic Stem Cell-Derived Cardiomyocytes Leads to Proarrhythmic Changes in In Vitro Cocultures. AB - Transplantation of stem cell-derived cardiomyocytes is one of the most promising therapeutic approaches after myocardial infarction, as loss of cardiomyocytes is virtually irreversible by endogenous repair mechanisms. In myocardial scars, transplanted cardiomyocytes will be in immediate contact with cardiac fibroblasts. While it is well documented how the electrophysiology of neonatal cardiomyocytes is modulated by cardiac fibroblasts of the same developmental stage, it is unknown how adult cardiac fibroblasts (aCFs) affect the function of embryonic stem cell-derived cardiomyocytes (ESC-CMs). To investigate the effects of aCFs on ESC-CM electrophysiology, we performed extra- and intracellular recordings of murine aCF-ESC-CM cocultures. We observed that spontaneous beating behaviour was highly irregular in aCF-ESC-CM cocultures compared to cocultures with mesenchymal stem cells (coefficient of variation of the interspike interval: 40.5 +/- 15.2% versus 9.3 +/- 2.0%, p = 0.008) and that action potential amplitude and maximal upstroke velocity (V max) were reduced (amplitude: 52.3 +/- 1.7 mV versus 65.1 +/- 1.5 mV, V max: 7.0 +/- 1.0 V/s versus 36.5 +/- 5.3 V/s), while action potential duration (APD) was prolonged (APD50: 25.6 +/- 1.0 ms versus 16.8 +/- 1.9 ms, p < 0.001; APD90: 52.2 +/- 1.5 ms versus 43.3 +/- 3.3 ms, p < 0.01) compared to controls. Similar changes could be induced by aCF conditioned medium. We conclude that the presence of aCFs changes automaticity and induces potentially proarrhythmic changes of ESC-CM electrophysiology. PMID- 26880950 TI - Revisiting Epithelial-to-Mesenchymal Transition in Liver Fibrosis: Clues for a Better Understanding of the "Reactive" Biliary Epithelial Phenotype. AB - Whether liver epithelial cells contribute to the development of hepatic scarring by undergoing epithelial-to-mesenchymal transition (EMT) is a controversial issue. Herein, we revisit the concept of EMT in cholangiopathies, a group of severe hepatic disorders primarily targeting the bile duct epithelial cell (cholangiocyte), leading to progressive portal fibrosis, the main determinant of liver disease progression. Unfortunately, therapies able to halt this process are currently lacking. In cholangiopathies, fibrogenesis is part of ductular reaction, a reparative complex involving epithelial, mesenchymal, and inflammatory cells. Ductular reactive cells (DRC) are cholangiocytes derived from the activation of the hepatic progenitor cell compartment. These cells are arranged into irregular strings and express a "reactive" phenotype, which enables them to extensively crosstalk with the other components of ductular reaction. We will first discuss EMT in liver morphogenesis and then highlight how some of these developmental programs are partly reactivated in DRC. Evidence for "bona fide" EMT changes in cholangiocytes is lacking, but expression of some mesenchymal markers represents a fundamental repair mechanism in response to chronic biliary damage with potential harmful fibrogenetic effects. Understanding microenvironmental cues and signaling perturbations promoting these changes in DRC may help to identify potential targets for new antifibrotic therapies in cholangiopathies. PMID- 26880952 TI - BMSCs Interactions with Adventitial Fibroblasts Display Smooth Muscle Cell Lineage Potential in Differentiation and Migration That Contributes to Neointimal Formation. AB - In this study a model of simulated vascular injury in vitro was used to study the characterization of bone-marrow-derived mesenchymal stem cells (BMSCs) morphology and to investigate the differentiation and migration of BMSCs in the presence of adventitial fibroblasts. BMSCs from rats were indirectly cocultured with adventitial fibroblasts in a transwell chamber apparatus for 7 days, and clonogenic assays demonstrated that BMSCs could be differentiated into smooth muscle-like cells with this process, including smooth muscle alpha-actin (alpha SMA) expression by immunofluorescence staining. Cell morphology of BMSCs was assessed by inverted microscope, while cell proliferation was assessed by MTT assay. The expressions of TGF-beta1, MMP-1, and NF-kappaB were detected by immunofluorescence staining and Smad3 mRNA was measured by reverse transcription PCR. Migration ability of BMSCs with DAPI-labeled nuclei was measured by laser confocal microscopy. Our results demonstrate that indirect interactions with adventitial fibroblasts can induce proliferation, differentiation, and migration of BMSCs that can actively participate in neointimal formation. Our results indicate that the pathogenesis of vascular remodeling might perform via TGF beta1/Smad3 signal transduction pathways. PMID- 26880951 TI - In Vivo Tracking of Cell Therapies for Cardiac Diseases with Nuclear Medicine. AB - Even though heart diseases are amongst the main causes of mortality and morbidity in the world, existing treatments are limited in restoring cardiac lesions. Cell transplantations, originally developed for the treatment of hematologic ailments, are presently being explored in preclinical and clinical trials for cardiac diseases. Nonetheless, little is known about the possible efficacy and mechanisms for these therapies and they are the center of continuous investigation. In this scenario, noninvasive imaging techniques lead to greater comprehension of cell therapies. Radiopharmaceutical cell labeling, firstly developed to track leukocytes, has been used successfully to evaluate the migration of cell therapies for myocardial diseases. A substantial rise in the amount of reports employing this methodology has taken place in the previous years. We will review the diverse radiopharmaceuticals, imaging modalities, and results of experimental and clinical studies published until now. Also, we report on current limitations and potential advances of radiopharmaceutical labeling for cell therapies in cardiac diseases. PMID- 26880953 TI - Wound Dressing Model of Human Umbilical Cord Mesenchymal Stem Cells-Alginates Complex Promotes Skin Wound Healing by Paracrine Signaling. AB - Purpose. To probe growth characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) cultured with alginate gel scaffolds, and to explore feasibility of wound dressing model of hUCMSCs-alginates compound. Methods. hUCMSCs were isolated, cultured, and identified in vitro. Then cells were cultivated in 100 mM calcium alginate gel, and the capacity of proliferation and migration and the expression of vascular endothelial growth factors (VEGF) were investigated regularly. Wound dressing model of hUCMSCs-alginate gel mix was transplanted into Balb/c mice skin defects. Wound healing rate and immunohistochemistry were examined. Results. hUCMSCs grew well but with little migration ability in the alginate gel. Compared with control group, a significantly larger cell number and more VEGF expression were shown in the gel group after culturing for 3-6 days (P < 0.05). In addition, a faster skin wound healing rate with more neovascularization was observed in the hUCMSCs-alginate gel group than in control groups at 15th day after surgery (P < 0.05). Conclusion. hUCMSCs can proliferate well and express massive VEGF in calcium alginate gel porous scaffolds. Wound dressing model of hUCMSCs-alginate gel mix can promote wound healing through paracrine signaling. PMID- 26880954 TI - Comparative Analysis of Human Mesenchymal Stem Cells from Umbilical Cord, Dental Pulp, and Menstrual Blood as Sources for Cell Therapy. AB - Although mesenchymal stem cells (MSCs) based therapy has been considered as a promising tool for tissue repair and regeneration, the optimal cell source remains unknown. Umbilical cord (UC), dental pulp (DP), and menstrual blood (MB) are easily accessible sources, which make them attractive candidates for MSCs. The goal of this study was to compare the biological characteristics, including morphology, proliferation, antiapoptosis, multilineage differentiation capacity, and immunophenotype of UC-, DP-, and MB-MSCs in order to provide a theoretical basis for clinical selection and application of these cells. As a result, all UC , DP-, and MB-MSCs have self-renewal capacity and multipotentiality. However, the UC-MSCs seemed to have higher cell proliferation ability, while DP-MSCs may have significant advantages for osteogenic differentiation, lower cell apoptosis, and senescence. These differences may be associated with the different expression level of cytokines, including vascular endothelial growth factor, fibroblast growth factor, keratinocyte growth factor, and hepatocyte growth factor in each of the MSCs. Comprehensively, our results suggest DP-MSCs may be a desired source for clinical applications of cell therapy. PMID- 26880955 TI - Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin. AB - Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone. PMID- 26880957 TI - Hijacking the Cellular Mail: Exosome Mediated Differentiation of Mesenchymal Stem Cells. AB - Bone transplantation is one of the most widely performed clinical procedures. Consequently, bone regeneration using mesenchymal stem cells and tissue engineering strategies is one of the most widely researched fields in regenerative medicine. Recent scientific consensus indicates that a biomimetic approach is required to achieve proper regeneration of any tissue. Exosomes are nanovesicles secreted by cells that act as messengers that influence cell fate. Although exosomal function has been studied with respect to cancer and immunology, the role of exosomes as inducers of stem cell differentiation has not been explored. We hypothesized that exosomes can be used as biomimetic tools for regenerative medicine. In this study we have explored the use of cell-generated exosomes as tools to induce lineage specific differentiation of stem cells. Our results indicate that proosteogenic exosomes isolated from cell cultures can induce lineage specific differentiation of naive MSCs in vitro and in vivo. Additionally, exosomes can also bind to matrix proteins such as type I collagen and fibronectin enabling them to be tethered to biomaterials. Overall, the results from this study show the potential of cell derived exosomes in bone regenerative medicine and opens up new avenues for future research. PMID- 26880956 TI - Stem/Progenitor Cell Niches Involved in Hepatic and Biliary Regeneration. AB - Niches containing stem/progenitor cells are present in different anatomical locations along the human biliary tree and within liver acini. The most primitive stem/progenitors, biliary tree stem/progenitor cells (BTSCs), reside within peribiliary glands located throughout large extrahepatic and intrahepatic bile ducts. BTSCs are multipotent and can differentiate towards hepatic and pancreatic cell fates. These niches' matrix chemistry and other characteristics are undefined. Canals of Hering (bile ductules) are found periportally and contain hepatic stem/progenitor cells (HpSCs), participating in the renewal of small intrahepatic bile ducts and being precursors to hepatocytes and cholangiocytes. The niches also contain precursors to hepatic stellate cells and endothelia, macrophages, and have a matrix chemistry rich in hyaluronans, minimally sulfated proteoglycans, fetal collagens, and laminin. The microenvironment furnishes key signals driving HpSC activation and differentiation. Newly discovered third niches are pericentral within hepatic acini, contain Axin2+ unipotent hepatocytic progenitors linked on their lateral borders to endothelia forming the central vein, and contribute to normal turnover of mature hepatocytes. Their relationship to the other stem/progenitors is undefined. Stem/progenitor niches have important implications in regenerative medicine for the liver and biliary tree and in pathogenic processes leading to diseases of these tissues. PMID- 26880959 TI - Endovascular Management of Aorta-Iliac Stenosis and Occlusive Disease by Kissing Stent Technique. AB - Kissing-stenting treatment has been used to treat patients with peripheral artery disease (PAD). However, the long term efficacy of the stenting therapy is not well defined in Chinese PAD patients. To investigate the question, sixty-three PAD patients (37 males and 26 females), aged 66 +/- 7.3 years, were analysed in the study. They were featured as claudication (n = 45, 71.4%), rest pain (n = 18, 28.6%), or gangrene (n = 8, 12.7%). In total, 161 stents were applied in aorta iliac lesions with 2.6 stents for each patient, including 55 self-expanding stents, 98 balloon expandable stents, and 8 covered stents. The success rate of implanting Kissing-stents was 100%. Catheter-directed thrombolysis (CDT) with urokinase was performed in 8 cases (12.7%). The severity of peripheral ischemia was significantly improved, as evidenced by 3.3-fold increase of ankle-brachial pressure index (ABI) after the surgery (P = 0.008). One, three, five, and seven years after surgery, the primary patency rate was 87.3%, 77.4%, 71.1%, and 65.0%, whereas the secondary patency rate was 95.2%, 92.5%, 89.5%, and 85.0%, respectively. No in-hospital mortality was recorded. In conclusion, Kissing stenting technique for aorta-iliac lesions is safe and effective with lower complications. It is beneficial for aorta-iliac occlusions that are longer than 60 mm. PMID- 26880958 TI - Multipotent Mesenchymal Stem Cell Treatment for Discogenic Low Back Pain and Disc Degeneration. AB - Low back pain with resultant loss of function, decreased productivity, and high economic costs is burdensome for both the individual and the society. Evidence suggests that intervertebral disc pathology is a major contributor to spine related pain and degeneration. When commonly used conservative therapies fail, traditional percutaneous or surgical options may be beneficial for pain relief but are suboptimal because of their inability to alter disc microenvironment catabolism, restore disc tissue, and/or preserve native spine biomechanics. Percutaneously injected Multipotent Mesenchymal Stem Cell (MSC) therapy has recently gained clinical interest for its potential to revolutionarily treat disc generated (discogenic) pain and associated disc degeneration. Unlike previous therapies to date, MSCs may uniquely offer the ability to improve discogenic pain and provide more sustained improvement by reducing disc microenvironment catabolism and regenerating disc tissue. Consistent treatment success has the potential to create a paradigm shift with regards to the treatment of discogenic pain and disc degeneration. PMID- 26880960 TI - Stem Cell Mobilization with G-CSF versus Cyclophosphamide plus G-CSF in Mexican Children. AB - Fifty-six aphaereses were performed in 23 pediatric patients with malignant hematological and solid tumors, following three different protocols for PBPC mobilization and distributed as follows: A: seventeen mobilized with 4 g/m(2) of cyclophosphamide (CFA) and 10 MUg/kg/day of granulocyte colony stimulating factor (G-CSF), B: nineteen with CFA + G-CSF, and C: twenty only with G-CSF when the WBC count exceeded 10 * 10(9)/L. The average number of MNC/kg body weight (BW)/aphaeresis was 0.4 * 10(8) (0.1-1.4), 2.25 * 10(8) (0.56-6.28), and 1.02 * 10(8) (0.34-2.5) whereas the average number of CD34+ cells/kg BW/aphaeresis was 0.18 * 10(6)/kg (0.09-0.34), 1.04 * 10(6) (0.19-9.3), and 0.59 * 10(6) (0.17 0.87) and the count of CFU/kg BW/aphaeresis was 1.11 * 10(5) (0.31-2.12), 1.16 * 10(5) (0.64-2.97), and 1.12 * 10(5) (0.3-6.63) in groups A, B, and C, respectively. The collection was better in group B versus group A (p = 0.007 and p = 0.05, resp.) and in group C versus group A (p = 0.08 and p = 0.05, resp.). The collection of PBPCs was more effective in the group mobilized with CFM + G CSF when the WBC exceeded 10 * 10(3)/MUL in terms of MNC and CD34+ cells and there was no toxicity of the chemotherapy. PMID- 26880961 TI - Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors. AB - Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents. PMID- 26880962 TI - The Progress of Induced Pluripotent Stem Cells as Models of Parkinson's Disease. AB - In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson's disease (PD). Somatic cells from patients with SNCA (alpha-synuclein), LRRK2 (leucine-rich repeat kinase 2), PINK1 (PTEN induced putative kinase 1), Parkin mutations, and at-risk individuals carrying GBA (beta-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, including alpha-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application. PMID- 26880963 TI - Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues. AB - Induced pluripotent stem cells (iPSC) are a most promising approach to the development of a hepatocyte transplantable mass sufficient to induce long-term correction of inherited liver metabolic diseases, thus avoiding liver transplantation. Their intrinsic self-renewal ability and potential to differentiate into any of the three germ layers identify iPSC as the most promising cell-based therapeutics, but also as drivers of tumor development. Teratoma development currently represents the gold standard to assess iPSC pluripotency. We analyzed the tumorigenic potential of iPSC generated from human hepatocytes (HEP-iPSC) and compared their immunohistochemical profiles to that of tumors developed from fibroblast and hematopoietic stem cell-derived iPSC. HEP iPSC generated tumors significantly presented more malignant morphological features than reprogrammed fibroblasts or CD34+ iPSC. Moreover, the protooncogene myc showed the strongest expression in HEP-iPSC, compared to only faint expression in the other cell subsets. Random integration of transgenes and the use of potent protooncogenes such as myc might be a risk factor for malignant tumor development if hepatocytes are used for reprogramming. Nonviral vector delivery systems or reprogramming of cells obtained from less invasive harvesting methods would represent interesting options for future developments in stem cell based approaches for liver metabolic diseases. PMID- 26880964 TI - Evaluating the Impact of Human Amnion Epithelial Cells on Angiogenesis. AB - The effects of human amnion epithelial cells (hAECs) on angiogenesis remain controversial. It is yet unknown if the presence of inflammation and/or gestational age of hAEC donors have an impact on angiogenesis. In this study, we examined the differences between term and preterm hAECs on angiogenesis in vitro and in vivo. Conditioned media from term hAECs induced the formation of longer huVEC tubules on Matrigel. Both term and preterm hAECs expressed VEGFA, PDGFB, ANGPT1, and FOXC1, which significantly increased after TNFalpha and IFNgamma stimulation. In the presence of TNFalpha and IFNgamma, coculture with term hAECs reduced gene transcription of Tie-2 and Foxc1 in huVECs, while coculture with preterm hAECs increased gene transcription of PDGFRalpha and PDGFRbeta and reduced gene transcription of FOXC1 in huVECs. In vivo assessment of angiogenesis using vWF immunostaining revealed that hAEC treatment decreased angiogenesis in a bleomycin model of lung fibrosis but increased angiogenesis in a neonatal model of hyperoxia-induced lung injury. In summary, our findings suggested that the impact of hAECs on angiogenesis may be influenced by the presence of inflammation and underlying pathology. PMID- 26880965 TI - Tissue-Related Hypoxia Attenuates Proinflammatory Effects of Allogeneic PBMCs on Adipose-Derived Stromal Cells In Vitro. AB - Human adipose tissue-stromal derived cells (ASCs) are considered a perspective tool for regenerative medicine. Depending on the application mode ASC/allogeneic immune cell interaction can occur in the systemic circulation under plenty high concentrations of O2 and in target tissues at lower O2 levels. Here we examined the effects of allogeneic PHA-stimulated peripheral blood mononuclear cells (PBMCs) on ASCs under ambient (20%) oxygen and "physiological" hypoxia (5% O2). As revealed with microarray analysis ASCs under 20% O2 were more affected by activated PBMCs, which was manifested in differential expression of more than 300 genes, whereas under 5% O2 only 140 genes were changed. Altered gene pattern was only partly overlapped at different O2 conditions. Under O2 ASCs retained their proliferative and differentiative capacities, mesenchymal phenotype, and intracellular organelle' state. ASCs were proinflammatory activated on transcription level that was confirmed by their ability to suppress activation and proliferation of mitogen-stimulated PBMCs. ASC/PBMCs interaction resulted in anti-inflammatory shift of paracrine mediators in conditioning medium with significant increase of immunosuppressive LIF level. Our data indicated that under both ambient and tissue-related O2 ASCs possessed immunosuppressive potential and maintained functional activity. Under "physiological" hypoxia ASCs were less susceptible to "priming" by allogeneic mitogen-activated PBMCs. PMID- 26880966 TI - The Androgen Receptor Bridges Stem Cell-Associated Signaling Nodes in Prostate Stem Cells. AB - The therapeutic potential of stem cells relies on dissecting the complex signaling networks that are thought to regulate their pluripotency and self renewal. Until recently, attention has focused almost exclusively on a small set of "core" transcription factors for maintaining the stem cell state. It is now clear that stem cell regulatory networks are far more complex. In this review, we examine the role of the androgen receptor (AR) in coordinating interactions between signaling nodes that govern the balance of cell fate decisions in prostate stem cells. PMID- 26880967 TI - Wharton's Jelly-Derived Mesenchymal Stromal Cells and Fibroblast-Derived Extracellular Matrix Synergistically Activate Apoptosis in a p21-Dependent Mechanism in WHCO1 and MDA MB 231 Cancer Cells In Vitro. AB - The tumour microenvironment plays a crucial role in tumour progression and comprises tumour stroma which is made up of different cell types and the extracellular matrix (ECM). Mesenchymal stromal cells (MSCs) are part of the tumour stroma and may have conflicting effects on tumour growth. In this study we investigated the effect of Wharton's Jelly-derived MSCs (WJ-MSCs) and a fibroblast-derived ECM (fd-ECM) on esophageal (WHCO1) and breast (MDA MB 231) cancer cells in vitro. Both WJ-MSCs and the fd-ECM, alone or in combination, downregulate PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulate p53 and p21. p21 induction resulted in G2 phase cell cycle arrest and induced apoptosis in vitro. Our data suggest that p21 induction is via p53-dependent and p53 independent mechanisms in WHCO1 and MDA MB 231 cells, respectively. Vascular endothelial growth factor, Akt, and Nodal pathways were downregulated in cancer cells cocultured with WJ-MSCs. We also demonstrate that WJ-MSCs effects on cancer cells appear to be short-lived whilst the fd-ECM effect is long-lived. This study shows the influence of tumour microenvironment on cancer cell behaviour and provides alternative therapeutic targets for potential regulation of tumour cells. PMID- 26880968 TI - Inhibition of JAK-STAT ERK/MAPK and Glycogen Synthase Kinase-3 Induces a Change in Gene Expression Profile of Bovine Induced Pluripotent Stem Cells. AB - Pluripotent stem cells (PSCs) fall in two states, one highly undifferentiated, the naive state, and the primed state, characterized by the inability to contribute to germinal lineage. Several reports have demonstrated that these states can be modified by changes to the cell culture conditions. With the advent of nuclear reprogramming, bovine induced pluripotent stem cells (biPSCs) have been generated. These cells represent examples of a transient-intermediate state of pluripotency with remarkable characteristics and biotechnological potential. Herein, we generated and characterized biPSC. Next, we evaluated different culture conditions for the ability to affect the expression of the set of core pluripotent transcription factors in biPSC. It was found that the use of 6 bromoindirubin-3-oxime and Sc1 inhibitors alone or in combination with 5-AzaC induced significantly higher levels of expression of endogenous REX1, OCT4, NANOG, and SOX2. Furthermore, LIF increased the levels of expression of OCT4 and REX1, compared with those cultured with LIF + bFGF. By contrast, bFGF decreased the levels of expression for both REX1 and OCT4. These results demonstrate that the biPSC gene expression profile is malleable by modification of the cell culture conditions well after nuclear reprogramming, and the culture conditions may determine their differentiation potential. PMID- 26880969 TI - Formation of Tumorspheres with Increased Stemness without External Mitogens in a Lung Cancer Model. AB - Like with most solid tumors, the presence of a subpopulation of cancer stem cells (CSCs) or cancer stem-like cells (CS-LCs) has been associated with chemoresistance and tumor relapse in lung cancer cells. In the absence of serum, CSCs/CS-LCs have the ability to grow as lung tumorspheres (LTSs), and this system is routinely used for isolation and characterization of putative CSCs/CS-LCs. Methods to isolate LTSs are usually performed in serum-free media supplemented with specific additives such as epidermal growth factor and basic fibroblast growth factor. In this study, we report the generation of LTSs without the addition of any external mitogenic stimulation. LTSs generated in this manner demonstrated several traits usually associated with increased stemness such as elevated expression of the stemness-associated marker Sox2 and increased chemoresistance to conventional anticancer drugs. In addition, we report that the FDA-approved drug Digitoxin, at concentration close to its therapeutic level, decreased the viability of LTSs and downregulated Sox2 independent of the PI3K/AKT pathway. The potential use of LTSs generated without the addition of any external mitogenic stimulation to study the role of specific factor(s) associated with stemness properties is also discussed. PMID- 26880970 TI - The Effect of Culture on Human Bone Marrow Mesenchymal Stem Cells: Focus on DNA Methylation Profiles. AB - Human bone marrow mesenchymal stem cells (hBM-MSCs) are the best characterized multipotent adult stem cells. Their self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties have indicated that they can be used in many clinical therapies. In a previous work we studied the DNA methylation levels of hBM-MSC genomic DNA in order to delineate a kind of methylation signature specific for early and late passages of culture. In the present work we focused on the modification of the methylation profiles of the X chromosome and imprinted loci, as sites expected to be more stable than whole genome. We propose a model where cultured hBM-MSCs undergo random modifications at the methylation level of most CGIs, nevertheless reflecting the original methylation status. We also pointed out global genome-wide demethylation connected to the long-term culture and senescence. Modification at CGIs promoters of specific genes could be related to the decrease in adipogenic differentiation potential. In conclusion, we showed important changes in CGIs methylation due to long-term in vitro culture that may affect the differentiation potential of hBM MSCs. Therefore it is necessary to optimize the experimental conditions for in vitro expansion in order to minimize these epigenetic changes and to standardize safer procedures. PMID- 26880971 TI - DNA Methylation in Skeletal Muscle Stem Cell Specification, Proliferation, and Differentiation. AB - An unresolved and critically important question in skeletal muscle biology is how muscle stem cells initiate and regulate the genetic program during muscle development. Epigenetic dynamics are essential for cellular development and organogenesis in early life and it is becoming increasingly clear that epigenetic remodeling may also be responsible for the cellular adaptations that occur in later life. DNA methylation of cytosine bases within CpG dinucleotide pairs is an important epigenetic modification that reduces gene expression when located within a promoter or enhancer region. Recent advances in the field suggest that epigenetic regulation is essential for skeletal muscle stem cell identity and subsequent cell development. This review summarizes what is currently known about how skeletal muscle stem cells regulate the myogenic program through DNA methylation, discusses a novel role for metabolism in this process, and addresses DNA methylation dynamics in adult skeletal muscle in response to physical activity. PMID- 26880972 TI - iPSCs: A Minireview from Bench to Bed, including Organoids and the CRISPR System. AB - When Dolly the sheep was born, the first probe into an adult mammalian genome traveling back in time and generating a whole new animal appeared. Ten years later, the reprogramming process became a defined method of producing induced pluripotent stem cells (iPSCs) through the overexpression of four transcription factors. iPSCs are capable of originating virtually all types of cells and tissues, including a whole new animal. The reprogramming strategies based on patient-derived cells should make the development of clinical applications of cell based therapy much more straightforward. Here, we analyze the current state, opportunities, and challenges of iPSCs from bench to bed, including organoids and the CRISPR system. PMID- 26880974 TI - Subculture of Germ Cell-Derived Colonies with GATA4-Positive Feeder Cells from Neonatal Pig Testes. AB - Enrichment of spermatogonial stem cells is important for studying their self renewal and differentiation. Although germ cell-derived colonies (GDCs) have been successfully cultured from neonatal pig testicular cells under 31 degrees C conditions, the short period of in vitro maintenance (<2 months) limited their application to further investigations. To develop a culture method that allows for in vitro maintenance of GDCs for long periods, we subcultured the GDCs with freshly prepared somatic cells from neonatal pig testes as feeder cells. The subcultured GDCs were maintained up to passage 13 with the fresh feeder cells (FFCs) and then frozen. Eight months later, the frozen GDCs could again form the colonies on FFCs as shown in passages 1 to 13. Immunocytochemistry data revealed that the FFCs expressed GATA-binding protein 4 (GATA4), which is also detected in the cells of neonatal testes and total testicular cells, and that the expression of GATA4 was decreased in used old feeder cells. The subcultured GDCs in each passage had germ and stem cell characteristics, and flow cytometric analyses revealed that ~60% of these cells were GFRalpha-1 positive. In conclusion, neonatal pig testes-derived GDCs can be maintained for long periods with GATA4 expressing testicular somatic cells. PMID- 26880975 TI - Residual Dyslipidemia Leads to Unfavorable Outcomes in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention. AB - Background. The present study aimed to evaluate the prevalence and prognosis of residual lipid abnormalities in statin-treated acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Subjects and Methods. A total of 3,047 ACS patients who underwent PCI and received statin therapy were included. Plasma concentrations of LDL-C, HDL-C, and TG were measured. For the follow-up study, major adverse cardiovascular cerebrovascular events (MACCE; including total death, cardiovascular death, myocardial infarction, and revascularization) were documented. Results. A total of 93.14% of all individuals were followed up for 18.1 months (range, 0-29.3 months). Of all 3,047 patients, those with a suboptimal goal were 67.75%, 85.85%, and 33.64% for LDL-C, HDL-C, and TG levels, respectively. Multiple Cox regression analysis revealed there were significant increases in cumulative MACCE of 41% (HR = 1.41, 95% CI [1.09-1.82], p = 0.008), and revascularization of 48% (HR = 1.48, 95% CI [1.10-1.99], p = 0.01) in low HDL-C patients with ACS after PCI, but not the high TG group at the end of study. Conclusions. Our results showed there is high rate of dyslipidemia in Chinese ACS patients after PCI. Importantly, low HDL-C but not high TG levels are associated with higher MACCE and revascularization rates in ACS patients after PCI. PMID- 26880973 TI - Pharmacological Therapy in the Heart as an Alternative to Cellular Therapy: A Place for the Brain Natriuretic Peptide? AB - The discovery that stem cells isolated from different organs have the ability to differentiate into mature beating cardiomyocytes has fostered considerable interest in developing cellular regenerative therapies to treat cardiac diseases associated with the loss of viable myocardium. Clinical studies evaluating the potential of stem cells (from heart, blood, bone marrow, skeletal muscle, and fat) to regenerate the myocardium and improve its functional status indicated that although the method appeared generally safe, its overall efficacy has remained modest. Several issues raised by these studies were notably related to the nature and number of injected cells, as well as the route and timing of their administration, to cite only a few. Besides the direct administration of cardiac precursor cells, a distinct approach to cardiac regeneration could be based upon the stimulation of the heart's natural ability to regenerate, using pharmacological approaches. Indeed, differentiation and/or proliferation of cardiac precursor cells is controlled by various endogenous mediators, such as growth factors and cytokines, which could thus be used as pharmacological agents to promote regeneration. To illustrate such approach, we present recent results showing that the exogenous administration of the natriuretic peptide BNP triggers "endogenous" cardiac regeneration, following experimental myocardial infarction. PMID- 26880976 TI - Prospect of Stem Cells in Bone Tissue Engineering: A Review. AB - Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes. PMID- 26880978 TI - Validation of Housekeeping Genes to Study Human Gingival Stem Cells and Their In Vitro Osteogenic Differentiation Using Real-Time RT-qPCR. AB - Gingival stem cells (GSCs) are recently isolated multipotent cells. Their osteogenic capacity has been validated in vitro and may be transferred to human cell therapy for maxillary large bone defects, as they share a neural crest cell origin with jaw bone cells. RT-qPCR is a widely used technique to study gene expression and may help us to follow osteoblast differentiation of GSCs. For accurate results, the choice of reliable housekeeping genes (HKGs) is crucial. The aim of this study was to select the most reliable HKGs for GSCs study and their osteogenic differentiation (dGSCs). The analysis was performed with ten selected HKGs using four algorithms: DeltaCt comparative method, GeNorm, BestKeeper, and NormFinder. This study demonstrated that three HKGs, SDHA, ACTB, and B2M, were the most stable to study GSC, whereas TBP, SDHA, and ALAS1 were the most reliable to study dGSCs. The comparison to stem cells of mesenchymal origin (ASCs) showed that SDHA/HPRT1 were the most appropriate for ASCs study. The choice of suitable HKGs for GSCs is important as it gave access to an accurate analysis of osteogenic differentiation. It will allow further study of this interesting stem cells source for future human therapy. PMID- 26880977 TI - Vitamin D and the Epithelial to Mesenchymal Transition. AB - Several studies support reciprocal regulation between the active vitamin D derivative 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) and the epithelial to mesenchymal transition (EMT). Thus, 1,25(OH)2D3 inhibits EMT via the induction of a variety of target genes that encode cell adhesion and polarity proteins responsible for the epithelial phenotype and through the repression of key EMT inducers. Both direct and indirect regulatory mechanisms mediate these effects. Conversely, certain master EMT inducers inhibit 1,25(OH)2D3 action by repressing the transcription of VDR gene encoding the high affinity vitamin D receptor that mediates 1,25(OH)2D3 effects. Consequently, the balance between the strength of 1,25(OH)2D3 signaling and the induction of EMT defines the cellular phenotype in each context. Here we review the current understanding of the genes and mechanisms involved in the interplay between 1,25(OH)2D3 and EMT. PMID- 26880979 TI - The Application of Human iPSCs in Neurological Diseases: From Bench to Bedside. AB - In principle, induced pluripotent stem cells (iPSCs) are generated from somatic cells by reprogramming and gaining the capacity to self-renew indefinitely as well as the ability to differentiate into cells of different lineages. Human iPSCs have absolute advantages over human embryonic stem cells (ESCs) and animal models in disease modeling, drug screening, and cell replacement therapy. Since Takahashi and Yamanaka first described in 2007 that iPSCs can be generated from human adult somatic cells by retroviral transduction of the four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, disease specific iPSC lines have sprung up worldwide like bamboo shoots after a spring rain, making iPSC one of the hottest and fastest moving topics in modern science. The craze for iPSCs has spread throughout main branches of clinical medicine, covering neurology, hematology, cardiology, endocrinology, hepatology, ophthalmology, and so on. Here in this paper, we will focus on the clinical application of human iPSCs in disease modeling, drug screening, and cell replacement therapy for neurological diseases. PMID- 26880982 TI - Bladder Smooth Muscle Cells Differentiation from Dental Pulp Stem Cells: Future Potential for Bladder Tissue Engineering. AB - Dental pulp stem cells (DPSCs) are multipotent cells capable of differentiating into multiple cell lines, thus providing an alternative source of cell for tissue engineering. Smooth muscle cell (SMC) regeneration is a crucial step in tissue engineering of the urinary bladder. It is known that DPSCs have the potential to differentiate into a smooth muscle phenotype in vitro with differentiation agents. However, most of these studies are focused on the vascular SMCs. The optimal approaches to induce human DPSCs to differentiate into bladder SMCs are still under investigation. We demonstrate in this study the ability of human DPSCs to differentiate into bladder SMCs in a growth environment containing bladder SMCs-conditioned medium with the addition of the transforming growth factor beta 1 (TGF-beta1). After 14 days of exposure to this medium, the gene and protein expression of SMC-specific marker (alpha-SMA, desmin, and calponin) increased over time. In particular, myosin was present in differentiated cells after 11 days of induction, which indicated that the cells differentiated into the mature SMCs. These data suggested that human DPSCs could be used as an alternative and less invasive source of stem cells for smooth muscle regeneration, a technology that has applications for bladder tissue engineering. PMID- 26880980 TI - The Importance of Ubiquitination and Deubiquitination in Cellular Reprogramming. AB - Ubiquitination of core stem cell transcription factors can directly affect stem cell maintenance and differentiation. Ubiquitination and deubiquitination must occur in a timely and well-coordinated manner to regulate the protein turnover of several stemness related proteins, resulting in optimal embryonic stem cell maintenance and differentiation. There are two switches: an E3 ubiquitin ligase enzyme that tags ubiquitin molecules to the target proteins for proteolysis and a second enzyme, the deubiquitinating enzyme (DUBs), that performs the opposite action, thereby preventing proteolysis. In order to maintain stemness and to allow for efficient differentiation, both ubiquitination and deubiquitination molecular switches must operate properly in a balanced manner. In this review, we have summarized the importance of the ubiquitination of core stem cell transcription factors, such as Oct3/4, c-Myc, Sox2, Klf4, Nanog, and LIN28, during cellular reprogramming. Furthermore, we emphasize the role of DUBs in regulating core stem cell transcriptional factors and their function in stem cell maintenance and differentiation. We also discuss the possibility of using DUBs, along with core transcription factors, to efficiently generate induced pluripotent stem cells. Our review provides a relatively new understanding regarding the importance of ubiquitination/deubiquitination of stem cell transcription factors for efficient cellular reprogramming. PMID- 26880983 TI - Stem Cell Therapy for Treatment of Stress Urinary Incontinence: The Current Status and Challenges. AB - Stress urinary incontinence (SUI) is a common urinary system disease that mostly affects women. Current treatments still do not solve the critical problem of urethral sphincter dysfunction. In recent years, there have been major developments in techniques to obtain, culture, and characterize autologous stem cells as well as many studies describing their applications for the treatment of SUI. In this paper, we review recent publications and clinical trials investigating the applications of several stem cell types as potential treatments for SUI and the underlying challenges of such therapy. PMID- 26880984 TI - Inhibition of Viability, Proliferation, Cytokines Secretion, Surface Antigen Expression, and Adipogenic and Osteogenic Differentiation of Adipose-Derived Stem Cells by Seven-Day Exposure to 0.5 T Static Magnetic Fields. AB - After seven-day exposure to 0.5-Tesla Static Magnetic Field (SMF), Adipose derived Stem Cells (ASCs) and those labeled by superparamagnetic iron oxide (SPIO) nanoparticles were examined for viability by methyl thiazol tetrazolium (MTT) assay, proliferation by cell counting and bromodeoxyuridine (BrdU) incorporation, DNA integrity by single cell gel electrophoresis, surface antigen by flow cytometry analysis, and the expression of cytokines and genetic markers by reverse transcription-PCR and underwent adipogenic and osteogenic differentiation assessed by quantifying related specific genes expression. The SMF slightly reduced cell viability and proliferation and inhibited the expression of CD49d, CD54, and CD73 but did not damage DNA integrity. The SMF slightly downregulated the expression of cytokines including Vascular Endothelial Growth Factor (VEGF), Insulin-like Growth Factor-1 (IGF-1), Transforming Growth Factor Beta 1 (TGF-beta1), genetic markers comprising Stem Cell Antigen-1 (Sca1), Octamer-4 (Oct-4), ATP-binding Cassette Subfamily B Member 1 (ABCB1), adipogenic marker genes containing Lipoprotein Lipase (LPL), Peroxisome Proliferator Activated Receptor Gamma (PPAR-gamma), and osteogenic marker genes including Secreted Phosphor-protein 1 (SPP1) and Osterix (OSX). Exposure to 0.5 T SMF for seven days inhibited viability, proliferation, surface antigen expression, cytokine secretion, stem cell genetic marker expression, and adipogenic and osteogenic differentiation but did not affect the DNA integrity in ASCs with or without SPIO labeling. PMID- 26880981 TI - Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance. AB - Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, "microvascular hyperplasia" is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs) reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a "quiescent" state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm. PMID- 26880986 TI - Cellular Model of Atherogenesis Based on Pluripotent Vascular Wall Pericytes. AB - Pericytes are pluripotent cells that can be found in the vascular wall of both microvessels and large arteries and veins. They have distinct morphology with long branching processes and form numerous contacts with each other and with endothelial cells, organizing the vascular wall cells into a three-dimensional network. Accumulating evidence demonstrates that pericytes may play a key role in the pathogenesis of vascular disorders, including atherosclerosis. Macrovascular pericytes are able to accumulate lipids and contribute to growth and vascularization of the atherosclerotic plaque. Moreover, they participate in the local inflammatory process and thrombosis, which can lead to fatal consequences. At the same time, pericytes can represent a useful model for studying the atherosclerotic process and for the development of novel therapeutic approaches. In particular, they are suitable for testing various substances' potential for decreasing lipid accumulation induced by the incubation of cells with atherogenic low-density lipoprotein. In this review we will discuss the application of cellular models for studying atherosclerosis and provide several examples of successful application of these models to drug research. PMID- 26880985 TI - Decellularized and Engineered Tendons as Biological Substitutes: A Critical Review. AB - Tendon ruptures are a great burden in clinics. Finding a proper graft material as a substitute for tendon repair is one of the main challenges in orthopaedics, for which the requirement of a biological scaffold would be different for each clinical application. Among biological scaffolds, the use of decellularized tendon-derived matrix increasingly represents an interesting approach to treat tendon ruptures. We analyzed in vitro and in vivo studies focused on the development of efficient protocols for the decellularization and for the cell reseeding of the tendon matrix to obtain medical devices for tendon substitution. Our review considered also the proper tendon source and preclinical animal models with the aim of entering into clinical trials. The results highlight a wide panorama in terms of allogenic or xenogeneic tendon sources, specimen dimensions, physical or chemical decellularization techniques, and the cell type variety for reseeding from terminally differentiated to undifferentiated mesenchymal stem cells and their static or dynamic culture employed to generate implantable constructs tested in different animal models. We try to identify the most efficient approach to achieve an optimal biological scaffold for biomechanics and intrinsic properties, resembling the native tendon and being applicable in clinics in the near future, with particular attention to the Achilles tendon substitution. PMID- 26880987 TI - Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia. AB - Even though clonally originated from a single cell, acute leukemia loses its homogeneity soon and presents at clinical diagnosis as a hierarchy of cells endowed with different functions, of which only a minority possesses the ability to recapitulate the disease. Due to their analogy to hematopoietic stem cells, these cells have been named "leukemia stem cells," and are thought to be chiefly responsible for disease relapse and ultimate survival after chemotherapy. Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) is cytogenetically characterized by either the t(8;21) or the inv(16)/t(16;16) chromosomal abnormalities, which, although being pathognomonic, are not sufficient per se to induce overt leukemia but rather determine a preclinical phase of disease when preleukemic subclones compete until the acquisition of clonal dominance by one of them. In this review we summarize the concepts regarding the application of the "leukemia stem cell" theory to the development of CBF AML; we will analyze the studies investigating the leukemogenetic role of t(8;21) and inv(16)/t(16;16), the proposed theories of its clonal evolution, and the role played by the hematopoietic niches in preserving the disease. Finally, we will discuss the clinical implications of stem cell modeling of CBF AML for the therapy of the disease. PMID- 26880989 TI - Hypoxia Inducible Factor-1alpha Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin alpha 4. AB - Although hypoxic environments have been known to regulate the migratory ability of bone marrow-derived mesenchymal stem cells (BM-MSCs), which is a critical factor for maximizing the therapeutic effect, the underlying mechanisms remain unclear. Therefore, we aimed to confirm the effect of hypoxia-inducible factor 1alpha (HIF-1alpha) on the migration of BM-MSCs and to analyze the interaction between HIF-1alpha and integrin-mediated signals. Hypoxia-activated HIF-1alpha significantly increased BM-MSC migration. The expression of integrin alpha 4 was decreased in BM-MSCs by increased HIF-1alpha under hypoxia, whereas the expression of Rho-associated kinase 1 (ROCK1) and Rac1/2/3 was increased. After downregulation of HIF-1alpha by YC-1, which is an inhibitor of HIF-1alpha, BM-MSC migration was decreased via upregulation of integrin alpha 4 and downregulation of ROCK1 and Rac1/2/3. Knockdown of integrin alpha 4 by integrin alpha 4 siRNA (siITGA4) treatment increased BM-MSC migration by upregulation of ROCK1, Rac1/2/3, and matrix metalloproteinase-2 regardless of oxygen tension. Moreover, siITGA4 treatment increased HIF-1alpha expression and augmented the translocation of HIF-1alpha into the nucleus under hypoxia. Taken together, the alternative expression of HIF-1alpha induced by microenvironment factors, such as hypoxia and integrin alpha 4, may regulate the migration of BM-MSCs. These findings may provide insights to the underlying mechanisms of BM-MSC migration for successful stem cell-based therapy. PMID- 26880988 TI - Glioma Stem Cells: Signaling, Microenvironment, and Therapy. AB - Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self-renewal and differentiation; glioblastoma derived GSCs are capable of de novo tumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs. PMID- 26880990 TI - Corrigendum to "Particle Radiation-Induced Nontargeted Effects in Bone-Marrow Derived Endothelial Progenitor Cells". AB - [This corrects the article DOI: 10.1155/2015/496512.]. PMID- 26880992 TI - In Vitro Expansion of Bone Marrow Derived Mesenchymal Stem Cells Alters DNA Double Strand Break Repair of Etoposide Induced DNA Damage. AB - Mesenchymal stem cells (MSCs) are of interest for use in diverse cellular therapies. Ex vivo expansion of MSCs intended for transplantation must result in generation of cells that maintain fidelity of critical functions. Previous investigations have identified genetic and phenotypic alterations of MSCs with in vitro passage, but little is known regarding how culturing influences the ability of MSCs to repair double strand DNA breaks (DSBs), the most severe of DNA lesions. To investigate the response to DSB stress with passage in vitro, primary human MSCs were exposed to etoposide (VP16) at various passages with subsequent evaluation of cellular damage responses and DNA repair. Passage number did not affect susceptibility to VP16 or the incidence and repair kinetics of DSBs. Nonhomologous end joining (NHEJ) transcripts showed little alteration with VP16 exposure or passage; however, homologous recombination (HR) transcripts were reduced following VP16 exposure with this decrease amplified as MSCs were passaged in vitro. Functional evaluations of NHEJ and HR showed that MSCs were unable to activate NHEJ repair following VP16 stress in cells after successive passage. These results indicate that ex vivo expansion of MSCs alters their ability to perform DSB repair, a necessary function for cells intended for transplantation. PMID- 26880993 TI - Induced Pluripotent Stem Cells: Generation Strategy and Epigenetic Mystery behind Reprogramming. AB - Possessing the ability of self-renewal with immortalization and potential for differentiation into different cell types, stem cells, particularly embryonic stem cells (ESC), have attracted significant attention since their discovery. As ESC research has played an essential role in developing our understanding of the mechanisms underlying reproduction, development, and cell (de)differentiation, significant efforts have been made in the biomedical study of ESC in recent decades. However, such studies of ESC have been hampered by the ethical issues and technological challenges surrounding them, therefore dramatically inhibiting the potential applications of ESC in basic biomedical studies and clinical medicine. Induced pluripotent stem cells (iPSCs), generated from the reprogrammed somatic cells, share similar characteristics including but not limited to the morphology and growth of ESC, self-renewal, and potential differentiation into various cell types. The discovery of the iPSC, unhindered by the aforementioned limitations of ESC, introduces a viable alternative to ESC. More importantly, the applications of iPSC in the development of disease models such as neurodegenerative disorders greatly enhance our understanding of the pathogenesis of such diseases and also facilitate the development of clinical therapeutic strategies using iPSC generated from patient somatic cells to avoid an immune rejection. In this review, we highlight the advances in iPSCs generation methods as well as the mechanisms behind their reprogramming. We also discuss future perspectives for the development of iPSC generation methods with higher efficiency and safety. PMID- 26880994 TI - iPSC-Derived Retinal Pigment Epithelium Allografts Do Not Elicit Detrimental Effects in Rats: A Follow-Up Study. AB - Phototransduction is accomplished in the retina by photoreceptor neurons and retinal pigment epithelium (RPE) cells. Photoreceptors rely heavily on the RPE, and death or dysfunction of RPE is characteristic of age-related macular degeneration (AMD), a very common neurodegenerative disease for which no cure exists. RPE replacement is a promising therapeutic intervention for AMD, and large numbers of RPE cells can be generated from pluripotent stem cells. However, questions persist regarding iPSC-derived RPE (iPS-RPE) viability, immunogenicity, and tumorigenesis potential. We showed previously that iPS-RPE prevent photoreceptor atrophy in dystrophic rats up until 24 weeks after implantation. In this follow-up study, we longitudinally monitored the same implanted iPS-RPE, in the same animals. We observed no gross abnormalities in the eyes, livers, spleens, brains, and blood in aging rats with iPSC-RPE grafts. iPS-RPE cells that integrated into the subretinal space outlived the photoreceptors and survived for as long as 2 1/2 years while nonintegrating RPE cells were ingested by host macrophages. Both populations could be distinguished using immunohistochemistry and electron microscopy. iPSC-RPE could be isolated from the grafts and maintained in culture; these cells also phagocytosed isolated photoreceptor outer segments. We conclude that iPS-RPE grafts remain viable and do not induce any obvious associated pathological changes. PMID- 26880995 TI - Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver. AB - The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs) mobilization and migration to the liver was poorly understood. Stromal cell derived factor-1 (SDF-1) participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver. PMID- 26880991 TI - The Rise of CRISPR/Cas for Genome Editing in Stem Cells. AB - Genetic manipulation is a powerful tool to establish the causal relationship between a genetic lesion and a particular pathological phenotype. The rise of CRISPR/Cas9 genome-engineering tools overcame the traditional technical bottleneck for routine site-specific genetic manipulation in cells. To create the perfect in vitro cell model, there is significant interest from the stem cell research community to adopt this fast evolving technology. This review addresses this need directly by providing both the up-to-date biochemical rationale of CRISPR-mediated genome engineering and detailed practical guidelines for the design and execution of CRISPR experiments in cell models. Ultimately, this review will serve as a timely and comprehensive guide for this fast developing technology. PMID- 26880996 TI - NK Cell and CD4+FoxP3+ Regulatory T Cell Based Therapies for Hematopoietic Stem Cell Engraftment. AB - Allogeneic hematopoietic cell transplantation (HCT) is a powerful therapy to treat multiple hematological diseases. The intensive conditioning regimens used to allow for donor hematopoietic stem cell (HSC) engraftment are often associated with severe toxicity, delayed immune reconstitution, life-threatening infections, and thus higher relapse rates. Additionally, due to the high incidence of graft versus host disease (GvHD), HCT protocols have evolved to prevent such disease that has a detrimental impact on antitumor and antiviral responses. Here, we analyzed the role of host T and natural killer (NK) cells in the rejection of donor HSC engraftment as well as the impact of donor regulatory T cells (Treg) and NK cells on HSC engraftment. We review some of the current strategies that utilize NK or Treg to improve allogeneic HCT therapy in order to accomplish better HSC engraftment and immune reconstitution and achieve a lower incidence of cancer relapse, opportunistic infections, and GvHD. PMID- 26880999 TI - Antimicrobial Resistance of Enteric Salmonella in Bangui, Central African Republic. AB - Introduction. The number of Salmonella isolated from clinical samples that are resistant to multiple antibiotics has increased worldwide. The aim of this study was to determine the prevalence of resistant Salmonella enterica isolated in Bangui. Methods. All enteric Salmonella strains isolated from patients in 2008 were identified and serotyped, and the phenotypes of resistance were determined by using the disk diffusion method. Nine resistance-associated genes, bla TEM , bla OXA , bla SHV , tetA, aadA1, catA1, dhfrA1, sul I, and sul II, were sought by genic amplification in seven S.e. Typhimurium strains. Results. The 94 strains isolated consisted of 47 S.e. Typhimurium (50%), 21 S.e. Stanleyville (22%), 18 S.e. Enteritidis (19%), 4 S.e. Dublin (4%), 4 S.e. Hadar (4%), and 1 S.e. Papuana (1%). Twenty-five (28%) were multiresistant, including 20 of the Typhimurium serovar (80%). Two main phenotypes of resistance were found: four antibiotics (56%) and to five antibiotics (40%). One S.e. Typhimurium isolate produced an extended-spectrum beta-lactamase (ESBL). Only seven strains of S.e. Typhimurium could be amplified genically. Only phenotypic resistance to tetracycline and aminosides was found. Conclusion. S. Typhimurium is the predominant serovar of enteric S. enterica and is the most widely resistant. The search for resistance genes showed heterogeneity of the circulating strains. PMID- 26880997 TI - Stem Cell Imaging: Tools to Improve Cell Delivery and Viability. AB - Stem cell therapy (SCT) has shown very promising preclinical results in a variety of regenerative medicine applications. Nevertheless, the complete utility of this technology remains unrealized. Imaging is a potent tool used in multiple stages of SCT and this review describes the role that imaging plays in cell harvest, cell purification, and cell implantation, as well as a discussion of how imaging can be used to assess outcome in SCT. We close with some perspective on potential growth in the field. PMID- 26881000 TI - Additional Effects of Back-Shu Electroacupuncture and Moxibustion in Cardioprotection of Rat Ischemia-Reperfusion Injury. AB - Many preclinical studies show that electroacupuncture (EA) on PC6 and ST36 can reduce infarct size after ischemia-reperfusion (IR) injury. Yet studies to enhance the treatment effect size are limited. The purpose of this study was to explore whether EA has additional myocardial protective effects on an ischemia reperfusion (IR) injury rat model when back-shu EA and moxibustion are added. SD rats were divided into several groups and treated with either EA only, EA + back shu EA (B), or EA + B + moxibustion (M) for 5 consecutive days. Transthoracic echocardiography and molecular and immunohistochemical evaluations were performed. It was found that although myocardial infarct areas were significantly lower and cardiac function was also significantly preserved in the three treatment groups compared to the placebo group, there were no additional differences between the three treatment groups. In addition, HSP20 and HSP27 were expressed significantly more in the treatment groups. The results suggest that adding several treatments does not necessarily increase protection. Our study corroborates previous findings that more treatment, such as prolonging EA duration or increasing EA intensity, does not always lead to better results. Other methods of increasing treatment effect size should be explored. PMID- 26880998 TI - Neuromuscular Regeneration: Perspective on the Application of Mesenchymal Stem Cells and Their Secretion Products. AB - Mesenchymal stem cells are posing as a promising character in the most recent therapeutic strategies and, since their discovery, extensive knowledge on their features and functions has been gained. In recent years, innovative sources have been disclosed in alternative to the bone marrow, conveying their associated ethical concerns and ease of harvest, such as the umbilical cord tissue and the dental pulp. These are also amenable of cryopreservation and thawing for desired purposes, in benefit of the donor itself or other patients in pressing need. These sources present promising possibilities in becoming useful cell sources for therapeutic applications in the forthcoming years. Effective and potential applications of these cellular-based strategies for the regeneration of peripheral nerve are overviewed, documenting recent advances and identified issues for this research area in the near future. Finally, besides the differentiation capacities attributed to mesenchymal stem cells, advances in the recognition of their effective mode of action in the regenerative theatre have led to a new area of interest: the mesenchymal stem cells' secretome. The paracrine modulatory pathway appears to be a major mechanism by which these are beneficial to nerve regeneration and comprehension on the specific growth factors, cytokine, and extracellular molecules secretion profiles is therefore of great interest. PMID- 26881001 TI - Ferulic Acid against Cyclophosphamide-Induced Heart Toxicity in Mice by Inhibiting NF-kappaB Pathway. AB - The purpose of the present study was to elucidate the protective effects of ferulic acid (FA) against cyclophosphamide- (CTX-) induced changes in mice. Forty eight male ICR mice were divided into four groups. Control group was intraperitoneally (i.p.) injected with 200 MUL of phosphate buffer saline (PBS). Model group was intraperitoneally injected with a single dose of CTX (200 mg/kg). FA (50 mg/kg) and FA (100 mg/kg) groups were intraperitoneally injected with a single dose of CTX (200 mg/kg) followed by the intragastric treatment with FA (50, 100 mg/kg) for 7 consecutive days. After 12 d, the mice were sacrificed to analyze the hematological, biochemical, histological parameters and mechanism research. The results indicated that FA significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), interleukin-6 (IL-6), IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) in CTX-injected mice. In addition, FA effectively reduced the total numbers of white blood cells (WBCs), red blood cells, platelets, and hemoglobin content. FA also obviously attenuated the histological changes of the heart tissues caused by CTX. Moreover, Western blot demonstrated that FA inhibited the phosphorylations of NF-kappaB signaling pathway in CTX-stimulated cardiac tissues. In conclusion, FA might be considered as an effective agent in the amelioration of the heart toxicity resulting from CTX treatment. PMID- 26881003 TI - Pharmacopuncture in Korea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - Background. Pharmacopuncture is a new form of acupuncture combining acupuncture with herbal medicine, and it has been used under various conditions in Korea. The aim of this study is to establish clinical evidence for the safety and efficacy of pharmacopuncture in Korea. Methods. We searched 9 databases and two relevant journals up to December 2014 using keywords, such as pharmacopuncture. All randomized, controlled trials evaluating pharmacopuncture under any conditions in Korea were considered. Results. Twenty-nine studies involving 1,211 participants were included. A meta-analysis of two studies on obesity showed that 5 to 8 weeks of pharmacopuncture reduced weight, waist circumference, and body mass index (BMI) more than normal saline injections. In the 5 studies of musculoskeletal conditions, 7 to 30 days of pharmacopuncture had additional effects on the reduction of pain intensity, and this benefit was maintained by limiting analyses to studies with a low risk of bias for randomization and/or allocation concealment. Conclusions. This systematic review suggests the potential of pharmacopuncture for obesity and musculoskeletal diseases. However, it is difficult to recommend pharmacopuncture as an evidence-based treatment because of methodological flaws and small sample sizes of the included studies. Further well designed trials are needed to draw a definitive conclusion. PMID- 26881002 TI - Ethnomedical Knowledge of Plants Used for the Treatment of Tuberculosis in Johor, Malaysia. AB - This study documented ethnomedical knowledge of plants used for the treatment of tuberculosis (TB) and its related symptoms as practiced by the Jakun community of Kampung Peta, situated in Endau Rompin Johor National Park, Johor, Malaysia. Eight key informants were selected by snowball sampling technique and data about medicinal plants were collected by semistructured interviews, participatory observations, and focus group. Qualitative analysis was undertaken using thematic analysis. There were 23 species of plants (22 genera, 20 families) documented and herbarium specimens were deposited at the UTHM Herbarium. Dipterocarpus sublamellatus was recorded for the first time with ethnomedical uses while other species were previously reported. The qualitative approach employed in this study demonstrates the emic perspective in terms of perceptions on traditional herbal medicine, transfer of knowledge, significant taboos related with medicinal plants, and their conservation efforts. Local and biomedical terminology in treatment of TB showed substantial correspondence. The outcomes obtained in the study are worth being further investigated for conservation strategies and are worthy of verifying their ethnomedical claims scientifically. PMID- 26881004 TI - The Status of Ethnobotanical Knowledge of Medicinal Plants and the Impacts of Resettlement in Delanta, Northwestern Wello, Northern Ethiopia. AB - The present study was conducted in Delanta (Ethiopia) to examine the use of medicinal plants and investigate the impacts of the 1984/85 resettlement program on the local people's knowledge on herbal medicine and its uses. The research was conducted with 72 informants in six study sites through semistructured interviews, group discussion, and market survey. In this study, 133 species belonging to 116 genera and 57 families were documented. These plants were mentioned for uses in the treatment of about 76 human and livestock ailments. The family Asteraceae was represented by the highest number with 14 species. Herbs accounted for 52.6% of the total species and leaves (32.6%) were the most frequently used parts. The analysis showed that the resettlement program has both positive and negative impacts on nature rehabilitation and local knowledge along with many human induced threats. Most of the plant knowledge is held by traditional healers and permanent residents. The people's preference for some medicinal plants gave indications of continuity of the ethnomedicinal information among the inhabitants. The findings inform that efforts need to be directed to in situ conservation in two of the plant community types which could protect a good proportion (about 50%) of the medicinal plant species. PMID- 26881005 TI - Experienced versus Inexperienced Interexaminer Reliability on Location and Classification of Myofascial Trigger Point Palpation to Diagnose Lateral Epicondylalgia: An Observational Cross-Sectional Study. AB - The purpose was to evaluate the interexaminer reliability of experienced and inexperienced examiners on location and classification of myofascial trigger points (MTrPs) in two epicondylar muscles and the association between the MTrP found and the diagnosis of lateral epicondylalgia (LE). Fifty-two pianists (some suffered LE) voluntarily participated in the study. Three physiotherapists (one inexperienced in myofascial pain) examined, located, and marked MTrPs in the extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC) muscles. Forearms were photographed and analyzed to establish the degree of agreement on MTrPs diagnosis. Data showed 81.73% and 77.88% of agreement on MTrP classification and 85.58% and 72.12% on MTrP location between the expert evaluators for ECRB and EDC, respectively. The agreement on MTrP classification between experienced and inexperienced examiners was 54.81% and 51.92% for ECRB and 50.00% and 55.77% for EDC. Also, agreement on MTrP location was 54.81% and 60.58% for ECRB and 48.08% and 48.08% for EDC. A strong association was found between presence of relevant MTrPs, LE diagnosis, and forearm pain when the examiners were experts. The analysis of location and classification of MTrPs in the epicondylar muscles through physical examination by experienced evaluators is reliable, reproducible, and suitable for diagnosing LE. PMID- 26881007 TI - Anti-Inflammatory and Antioxidant Activities of Salvia fruticosa: An HPLC Determination of Phenolic Contents. AB - Objectives. Salvia fruticosa Mill. (S. fruticosa) is widely used in folk medicine. Accordingly, the present study was designed to evaluate the antioxidant and anti-inflammatory activities of S. fruticosa, and to determine the phenolic constituents of its extracts. Methods. The antioxidant activity was determined using 2,2-diphenylpicrylhydrazyl assay. Total phenolic contents were estimated using Folin-Ciocalteu reagent, and high-performance liquid chromatography was performed to identify phenolic constituents. To evaluate the anti-inflammatory activity, carrageenan-induced mouse paw edema was determined plethysmographically. Key Findings. Different plant extracts demonstrated strong radical scavenging activity, where the ethyl acetate extract had the highest value in the roots and the lowest in the aerial parts. This antioxidant activity was correlated to the total phenolic content of different extracts, where rutin and luteolin were the most abundant constituents. Interestingly, both the roots and aerial parts revealed a significant anti-inflammatory activity comparable to diclofenac. Conclusions. This study is the first to demonstrate pharmacologic evidence of the potential anti-inflammatory activity of S. fruticosa. This activity may partly be due to the radical scavenging effects of its polyphenolic contents. These findings warrant the popular use of the East Mediterranean sage and highlight the potential of its active constituents in the development of new anti-inflammatory drugs. PMID- 26881006 TI - The Effect of External Apple Vinegar Application on Varicosity Symptoms, Pain, and Social Appearance Anxiety: A Randomized Controlled Trial. AB - Aim. We aimed to determine the effect of external apple vinegar application on the symptoms and social appearance anxiety of varicosity patients who were suggested conservative treatment. Method. The study was planned as an experimental, randomized, and controlled study. 120 patients were randomly selected and then were randomly allocated to either experimental or control group by simple blind random sampling method. In the collection of research data, a questionnaire questioning sociodemographic and clinical characteristics, the Visual Analog Scale (VAS) for pain, and the Social Appearance Anxiety Scale (SAAS) were used. The patients in the study group were suggested to apply apple vinegar to the area of the leg with varicosity alongside the treatment suggested by the doctor. The patients in the control group received no intervention during the study. Results. The sociodemographic and clinic characteristics of both groups were found to be similar (p > 0.05). The patients were evaluated with regard to cramps, pain, leg fatigue perception, edema, itching, pigmentation, and weight feelings in the leg, VAS, and SAAS averages in the second evaluation; the control group had a decrease in such symptoms (p > 0.05) although the decrease in the application group was higher and statistically meaningful (p < 0.05). Conclusion. We determined that the external application of apple vinegar on varicosity patients, which is a very easy application, increased the positive effects of conservative treatment. PMID- 26881008 TI - A Review of Techniques for Detection of Movement Intention Using Movement-Related Cortical Potentials. AB - The movement-related cortical potential (MRCP) is a low-frequency negative shift in the electroencephalography (EEG) recording that takes place about 2 seconds prior to voluntary movement production. MRCP replicates the cortical processes employed in planning and preparation of movement. In this study, we recapitulate the features such as signal's acquisition, processing, and enhancement and different electrode montages used for EEG data recoding from different studies that used MRCPs to predict the upcoming real or imaginary movement. An authentic identification of human movement intention, accompanying the knowledge of the limb engaged in the performance and its direction of movement, has a potential implication in the control of external devices. This information could be helpful in development of a proficient patient-driven rehabilitation tool based on brain computer interfaces (BCIs). Such a BCI paradigm with shorter response time appears more natural to the amputees and can also induce plasticity in brain. Along with different training schedules, this can lead to restoration of motor control in stroke patients. PMID- 26881009 TI - Diagnosing Parkinson's Diseases Using Fuzzy Neural System. AB - This study presents the design of the recognition system that will discriminate between healthy people and people with Parkinson's disease. A diagnosing of Parkinson's diseases is performed using fusion of the fuzzy system and neural networks. The structure and learning algorithms of the proposed fuzzy neural system (FNS) are presented. The approach described in this paper allows enhancing the capability of the designed system and efficiently distinguishing healthy individuals. It was proved through simulation of the system that has been performed using data obtained from UCI machine learning repository. A comparative study was carried out and the simulation results demonstrated that the proposed fuzzy neural system improves the recognition rate of the designed system. PMID- 26881010 TI - P300 Detection Based on EEG Shape Features. AB - We present a novel approach to describe a P300 by a shape-feature vector, which offers several advantages over the feature vector used by the BCI2000 system. Additionally, we present a calibration algorithm that reduces the dimensionality of the shape-feature vector, the number of trials, and the electrodes needed by a Brain Computer Interface to accurately detect P300s; we also define a method to find a template that best represents, for a given electrode, the subject's P300 based on his/her own acquired signals. Our experiments with 21 subjects showed that the SWLDA's performance using our shape-feature vector was 93%, that is, 10% higher than the one obtained with BCI2000-feature's vector. The shape-feature vector is 34-dimensional for every electrode; however, it is possible to significantly reduce its dimensionality while keeping a high sensitivity. The validation of the calibration algorithm showed an averaged area under the ROC (AUROC) curve of 0.88. Also, most of the subjects needed less than 15 trials to have an AUROC superior to 0.8. Finally, we found that the electrode C4 also leads to better classification. PMID- 26881011 TI - Systems Medicine of Cancer: Bringing Together Clinical Data and Nonlinear Dynamics of Genetic Networks. PMID- 26881012 TI - Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer. AB - Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID- 26881013 TI - Evaluation of Lasting Effects of Heat Stress on Sperm Profile and Oxidative Status of Ram Semen and Epididymal Sperm. AB - Higher temperatures lead to an increase of testicular metabolism that results in spermatic damage. Oxidative stress is the main factor responsible for testicular damage caused by heat stress. The aim of this study was to evaluate lasting effects of heat stress on ejaculated sperm and immediate or long-term effects of heat stress on epididymal sperm. We observed decrease in motility and mass motility of ejaculated sperm, as well as an increase in the percentages of sperm showing major and minor defects, damaged plasma and acrosome membranes, and a decrease in the percentage of sperm with high mitochondrial membrane potential in the treated group until one spermatic cycle. An increased enzymatic activity of glutathione peroxidase and an increase of stressed cells were observed in ejaculated sperm of the treated group. A decrease in the percentage of epididymal sperm with high mitochondrial membrane potential was observed in the treated group. However, when comparing immediate and long-term effects, we observed an increase in the percentage of sperm with low mitochondrial membrane potential. In conclusion, testicular heat stress induced oxidative stress that led to rescuable alterations after one spermatic cycle in ejaculated sperm and also after 30 days in epididymal sperm. PMID- 26881015 TI - Hypochlorite-Modified Albumin Upregulates ICAM-1 Expression via a MAPK-NF-kappaB Signaling Cascade: Protective Effects of Apocynin. AB - Hypochlorite-modified albumin (HOCl-alb) has been linked to endothelial dysfunction, which plays an important role in the development of hypertension, diabetes, and chronic kidney disease. However, whether HOCl-alb induces endothelial dysfunction via vascular inflammation and whether a signaling pathway is involved are unknown and have not been investigated. HOCl-alb was found to upregulate ICAM-1 expression in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. HOCl-alb time-dependently phosphorylated ERK1/2 and p38(MAPK). HOCl-alb also activated NF-kappaB. ICAM-1 expression was dose-dependently inhibited by U0126 (a specific inhibitor of MEK1/2, a signal upstream from ERK1/2), SB203580 (a specific inhibitor of p38(MAPK)), and SN50 (a specific inhibitor of NF-kappaB). U0126 and SB203580 both counteracted the activation of NF-kappaB, whereas the phosphorylation of ERK1/2 and p38(MAPK) was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, and p38(MAPK) activity was reduced by SB203580 but not by U0126. Apocynin, a specific NADPH oxidase (NOX) inhibitor, inhibited ICAM-1 expression and the activity of ERK1/2, p38(MAPK), and NF-kappaB. These results indicate that HOCl-alb-induced ICAM-1 expression is caused by the activation of a redox sensitive intracellular signal cascade involving ERK1/2 and p38(MAPK), culminating in the activation of NF-kappaB and involving NOXs among the upstream signals. PMID- 26881014 TI - Killing Me Softly: Connotations to Unfolded Protein Response and Oxidative Stress in Alzheimer's Disease. AB - This review is focused on the possible causes of mitochondrial dysfunction in AD, underlying molecular mechanisms of this malfunction, possible causes and known consequences of APP, Abeta, and hyperphosphorylated tau presence in mitochondria, and the contribution of altered lipid metabolism (nonsterol isoprenoids) to pathological processes leading to increased formation and accumulation of the aforementioned hallmarks of AD. Abnormal protein folding and unfolded protein response seem to be the outcomes of impaired glycosylation due to metabolic disturbances in geranylgeraniol intermediary metabolism. The origin and consecutive fate of APP, Abeta, and tau are emphasized on intracellular trafficking apparently influenced by inaccurate posttranslational modifications. We hypothesize that incorrect intracellular processing of APP determines protein translocation to mitochondria in AD. Similarly, without obvious reasons, the passage of Abeta and tau to mitochondria is observed. APP targeted to mitochondria blocks the activity of protein translocase complex resulting in poor import of proteins central to oxidative phosphorylation. Besides, APP, Abeta, and neurofibrillary tangles of tau directly or indirectly impair mitochondrial biochemistry and bioenergetics, with concomitant generation of oxidative/nitrosative stress. Limited protective mechanisms are inadequate to prevent the free radical-mediated lesions. Finally, neuronal loss is observed in AD-affected brains typically by pathologic apoptosis. PMID- 26881017 TI - Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments. AB - Diabetes mellitus leads to increased Advanced Glycation End Products (AGE) production, which has been associated with secondary diabetic complications. Type 1 diabetic patients undergoing pancreas-kidney transplantation (SPKT) can restore normoglycemia and renal function, eventually decreasing AGE accumulation. We aimed to prospectively study AGE evolution after SPKT. Circulating AGE were assessed in 20 patients, at time 0 (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after successful SPKT. Global AGE and carboxymethyllysine (CML) were analyzed, as well as advanced oxidation protein products (AOPP). Skin biopsies were obtained at T0 and T12. Immunohistochemistry with anti-AGE antibody evaluated skin AGE deposition. AGE mean values were 16.8 +/- 6.4 MUg/mL at T0; 17.1 +/- 3.8 MUg/mL at T3; 17.5 +/- 5.6 MUg/mL at T6; and 16.0 +/- 5.2 MUg/mL at T12. CML mean values were 0.94 +/- 0.36 ng/mL at T0; 1.11 +/- 0.48 ng/mL at T3; 0.99 +/- 0.42 ng/mL at T6; and 0.78 +/- 0.38 ng/mL at T12. AOPP mean values were 130.1 +/- 76.8 MUMol/L at T0; 137.3 +/- 110.6 MUMol/L at T3; 116.4 +/- 51.2 MUMol/L at T6; and 106.4 +/- 57.9 MUMol/L at T12. CML variation was significant (P = 0.022); AOPP variation was nearly significant (P = 0.076). Skin biopsies evolved mostly from a cytoplasmic diffuse to a peripheral interkeratinocytic immunoreaction pattern; in 7 cases, a reduction in AGE immunoreaction intensity was evident at T12. In conclusion, glycoxidation markers decrease, plasmatic and on tissues, may start early after SPKT. Studies with prolonged follow-up may confirm these data. PMID- 26881016 TI - 1,4-Dihydropyridine Derivatives: Dihydronicotinamide Analogues-Model Compounds Targeting Oxidative Stress. AB - Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry. PMID- 26881019 TI - Effects of Polyphenol, Measured by a Biomarker of Total Polyphenols in Urine, on Cardiovascular Risk Factors After a Long-Term Follow-Up in the PREDIMED Study. AB - Several epidemiological studies have shown an inverse association between the consumption of polyphenol-rich foods and risk of cardiovascular diseases. However, accuracy and reliability of these studies may be increased using urinary total polyphenol excretion (TPE) as a biomarker for total polyphenol intake. Our aim was to assess if antioxidant activity, measured by a Folin-Ciocalteu assay in urine, is correlated with an improvement in cardiovascular risk factors (blood pressure and serum glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations) in an elderly population at high risk. A longitudinal study was performed with 573 participants (aged 67.3 +/- 5.9) from the PREDIMED study (ISRCTN35739639). We used Folin-Ciocalteu method to determine TPE in urine samples, assisting with solid phase extraction. Participants were categorized into three groups according to changes in TPE. Multiple linear regression models were used to assess relationships between TPE and clinical cardiovascular risk factors, adjusting for potential confounders. After a 5-year follow-up, significant inverse correlations were observed between changes in TPE and plasma triglyceride concentration (beta = -8.563; P = 0.007), glucose concentration (beta = -4.164; P = 0.036), and diastolic blood pressure (beta = 1.316; P = 0.013). Our results suggest that the consumption of more polyphenols, measured as TPE in urine, could exert a protective effect against some cardiovascular risk factors. PMID- 26881018 TI - Dietary Phenolic Compounds Interfere with the Fate of Hydrogen Peroxide in Human Adipose Tissue but Do Not Directly Inhibit Primary Amine Oxidase Activity. AB - Resveratrol has been reported to inhibit monoamine oxidases (MAO). Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO) in peripheral organs, such as semicarbazide-sensitive AO (SSAO), known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid) behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2 generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2 detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [(14)C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2 produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO. PMID- 26881020 TI - It Is All about (U)biquitin: Role of Altered Ubiquitin-Proteasome System and UCHL1 in Alzheimer Disease. AB - Free radical-mediated damage to macromolecules and the resulting oxidative modification of different cellular components are a common feature of aging, and this process becomes much more pronounced in age-associated pathologies, including Alzheimer disease (AD). In particular, proteins are particularly sensitive to oxidative stress-induced damage and these irreversible modifications lead to the alteration of protein structure and function. In order to maintain cell homeostasis, these oxidized/damaged proteins have to be removed in order to prevent their toxic accumulation. It is generally accepted that the age-related accumulation of "aberrant" proteins results from both the increased occurrence of damage and the decreased efficiency of degradative systems. One of the most important cellular proteolytic systems responsible for the removal of oxidized proteins in the cytosol and in the nucleus is the proteasomal system. Several studies have demonstrated the impairment of the proteasome in AD thus suggesting a direct link between accumulation of oxidized/misfolded proteins and reduction of this clearance system. In this review we discuss the impairment of the proteasome system as a consequence of oxidative stress and how this contributes to AD neuropathology. Further, we focus the attention on the oxidative modifications of a key component of the ubiquitin-proteasome pathway, UCHL1, which lead to the impairment of its activity. PMID- 26881022 TI - Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells. AB - Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment. PMID- 26881023 TI - Lycopene Deficiency in Ageing and Cardiovascular Disease. AB - Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed. PMID- 26881021 TI - The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults. AB - The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration. PMID- 26881025 TI - Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis. AB - Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (?-)) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 +/- 8 mmHg in AdEmpty rats (n = 6), while rats overexpressing CuZnSOD (n = 8) in the OVLT demonstrated a blood pressure increase of only 18 +/- 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction of O2 (?-) in the OVLT plays an important role in the development of chronic AngII-dependent hypertension. PMID- 26881026 TI - Phenolic Rich Extract from Clinacanthus nutans Attenuates Hyperlipidemia Associated Oxidative Stress in Rats. AB - Clinacanthus nutans is used as traditional medicine in Asia but there are limited scientific studies to support its use. In this study, the stem and leaf of C. nutans were extracted using solvents of differing polarities, and their antioxidant capacities were determined using multiple antioxidant assays. The water and aqueous methanolic leaf extracts were further fractionated and their antioxidant capacities and phenolic compositions were tested. Furthermore, the efficacies of the water and aqueous methanolic leaf extracts were tested against hyperlipidemia-induced oxidative stress in rats. Serum and hepatic antioxidant and oxidative stress markers were tested after feeding the rats with high fat diet together with the extracts or simvastatin for 7 weeks. The results indicated that both leaf extracts attenuated oxidative stress through increasing serum antioxidant enzymes activity and upregulating the expression of hepatic antioxidant genes. Multiple phenolic compounds were detected in the extracts and fractions of C. nutans, although protocatechuic acid was one of the most abundant and may have contributed significantly towards the bioactivities of the extracts. However, synergistic effects of different phenolics may have contributed to the overall bioactivities. C. nutans can be a good source of functional ingredients for the management of oxidative stress-related diseases. PMID- 26881024 TI - Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases. AB - Oxidative stress results from a disturbed balance between oxidation and antioxidant systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) may be either harmful or beneficial to the cells. Ion channels are transmembrane proteins that participate in a large variety of cellular functions and have been implicated in the development of a variety of diseases. A significant amount of the available drugs in the market targets ion channels. These proteins have sulfhydryl groups of cysteine and methionine residues in their structure that can be targeted by ROS and RNS altering channel function including gating and conducting properties, as well as the corresponding signaling pathways associated. The regulation of ion channels by ROS has been suggested to be associated with some pathological conditions including liver diseases. This review focuses on understanding the role and the potential association of ion channels and oxidative stress in liver diseases including fibrosis, alcoholic liver disease, and cancer. The potential association between ion channels and oxidative stress conditions could be used to develop new treatments for major liver diseases. PMID- 26881029 TI - Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers. AB - Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories from omega-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories from omega-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against high omega-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to high omega-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with high omega-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and high omega-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis. PMID- 26881030 TI - Polydatin Attenuates H2O2-Induced Oxidative Stress via PKC Pathway. AB - Oxidative stress plays an important role in the pathogenesis of endothelial dysfunction, which is found to precede the development of diverse cardiovascular diseases (CVDs). The aim of this study was to observe the protective effects of PD against H2O2-induced oxidative stress injury (OSI) in human umbilical vein endothelial cells (HUVECs) and the possible mechanism of PD in OSI treatment. HUVECs were subjected to H2O2 in the absence or presence of PD. It turned out that PD improved cell viability and adhesive and migratory abilities, inhibited the release of lactate dehydrogenase (LDH) and reactive oxygen species (ROS), and elevated the content of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). TUNEL, fluorometric assays, and Western blotting showed that OSI upregulated the apoptosis ratio, the activity of caspase-3 and the level of proapoptotic protein Bax and decreased the level of antiapoptotic protein Bcl-2. However, PD treatment partially reversed these damage effects and Protein Kinase C (PKC) activation by thymeleatoxin (THX) in turn eliminated the antiapoptotic effect of PD. Furthermore, PD attenuated the H2O2-induced phosphorylation of PKCs alpha and delta and increased the phosphorylation of PKC epsilon. Our results indicated that PD might exert protective effects against OSI through various interactions with PKC pathway. PMID- 26881028 TI - Update on the Mechanisms of Pulmonary Inflammation and Oxidative Imbalance Induced by Exercise. AB - The mechanisms involved in the generation of oxidative damage and lung inflammation induced by physical exercise are described. Changes in lung function induced by exercise involve cooling of the airways, fluid evaporation of the epithelial surface, increased contact with polluting substances, and activation of the local and systemic inflammatory response. The present work includes evidence obtained from the different types of exercise in terms of duration and intensity, the effect of both acute performance and chronic performance, and the influence of special conditions such as cold weather, high altitude, and polluted environments. Levels of prooxidants, antioxidants, oxidative damage to biomolecules, and cellularity, as well as levels of soluble mediators of the inflammatory response and its effects on tissues, are described in samples of lung origin. These samples include tissue homogenates, induced sputum, bronchoalveolar lavage fluid, biopsies, and exhaled breath condensate obtained in experimental protocols conducted on animal and human models. Finally, the need to simultaneously explore the oxidative/inflammatory parameters to establish the interrelation between them is highlighted. PMID- 26881027 TI - Redox Control of Multidrug Resistance and Its Possible Modulation by Antioxidants. AB - Clinical efficacy of anticancer chemotherapies is dramatically hampered by multidrug resistance (MDR) dependent on inherited traits, acquired defence against toxins, and adaptive mechanisms mounting in tumours. There is overwhelming evidence that molecular events leading to MDR are regulated by redox mechanisms. For example, chemotherapeutics which overrun the first obstacle of redox-regulated cellular uptake channels (MDR1, MDR2, and MDR3) induce a concerted action of phase I/II metabolic enzymes with a temporal redox-regulated axis. This results in rapid metabolic transformation and elimination of a toxin. This metabolic axis is tightly interconnected with the inducible Nrf2-linked pathway, a key switch-on mechanism for upregulation of endogenous antioxidant enzymes and detoxifying systems. As a result, chemotherapeutics and cytotoxic by products of their metabolism (ROS, hydroperoxides, and aldehydes) are inactivated and MDR occurs. On the other hand, tumour cells are capable of mounting an adaptive antioxidant response against ROS produced by chemotherapeutics and host immune cells. The multiple redox-dependent mechanisms involved in MDR prompted suggesting redox-active drugs (antioxidants and prooxidants) or inhibitors of inducible antioxidant defence as a novel approach to diminish MDR. Pitfalls and progress in this direction are discussed. PMID- 26881031 TI - Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? AB - Oxidative stress has been implicated in many chronic diseases. However, antioxidant trials are so far largely unsuccessful as a preventive or curative measure. Chronic low-grade inflammatory process, on the other hand, plays a central role in the pathogenesis of a number of chronic diseases. Oxidative stress and inflammation are closely related pathophysiological processes, one of which can be easily induced by another. Thus, both processes are simultaneously found in many pathological conditions. Therefore, the failure of antioxidant trials might result from failure to select appropriate agents that specifically target both inflammation and oxidative stress or failure to use both antioxidants and anti-inflammatory agents simultaneously or use of nonselective agents that block some of the oxidative and/or inflammatory pathways but exaggerate the others. To examine whether the interdependence between oxidative stress and inflammation can explain the antioxidant paradox we discussed in the present review the basic aspects of oxidative stress and inflammation and their relationship and dependence. PMID- 26881032 TI - Mitochondrial Alterations in Peripheral Mononuclear Blood Cells from Alzheimer's Disease and Mild Cognitive Impairment Patients. AB - It is well recognized that mitochondrial dysfunction contributes to neurodegeneration occurring in Alzheimer's disease (AD). However, evidences of mitochondrial defects in AD peripheral cells are still inconclusive. Here, some mitochondrial-encoded and nuclear-encoded proteins, involved in maintaining the correct mitochondria machine, were investigated in terms of protein expression and enzymatic activity in peripheral blood mononuclear cells (PBMCs) isolated from AD and Mild Cognitive Impairment (MCI) patients and healthy subjects. In addition mitochondrial DNA copy number was measured by real time PCR. We found some differences and some similarities between AD and MCI patients when compared with healthy subjects. For example, cytochrome C and cytochrome B were decreased in AD, while MCI showed only a statistical reduction of cytochrome C. On the other hand, both AD and MCI blood cells exhibited highly nitrated MnSOD, index of a prooxidant environment inside the mitochondria. TFAM, a regulator of mitochondrial genome replication and transcription, was decreased in both AD and MCI patients' blood cells. Moreover also the mitochondrial DNA amount was reduced in PBMCs from both patient groups. In conclusion these data confirmed peripheral mitochondria impairment in AD and demonstrated that TFAM and mtDNA amount reduction could be two features of early events occurring in AD pathogenesis. PMID- 26881034 TI - Correlation of Oxidative and Antioxidative Processes in the Blood of Patients with Cervical Spinal Cord Injury. AB - The effect of cervical spinal cord injury (CSCI) on oxidative stress parameters was assessed. The study was conducted in 42 patients with CSCI (studied group), 15 patients with cerebral concussion, without CSCI (Control II), and 30 healthy volunteers (Control I). Blood was taken from the basilic vein: before and seven days after the spinal cord decompression surgery (mean time from CSCI to surgery: 8 hours) in the studied group and once in the controls. Thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) concentrations, and glutathione peroxidase (GPx), catalase (CAT), and creatine kinase (CK) activities before the surgery were higher in the studied group than in the controls. Reduced glutathione concentration was similar in all groups. Superoxide dismutase (SOD) in the studied group was 16% lower (P <= 0.001) than in Control I. Lipid peroxidation products, and GPx and CAT activities in erythrocytes seven days after the surgery were lower (P <= 0.001), while SOD was 25% higher (P <= 0.001) than before the surgery. CK in blood plasma after the surgery was 34% lower (P <= 0.001) than before it. CSCI is accompanied by oxidative stress. Surgical and pharmacological treatment helps to restore the oxidant-antioxidant balance. PMID- 26881033 TI - Hydrogen Sulfide and Cellular Redox Homeostasis. AB - Intracellular redox imbalance is mainly caused by overproduction of reactive oxygen species (ROS) or weakness of the natural antioxidant defense system. It is involved in the pathophysiology of a wide array of human diseases. Hydrogen sulfide (H2S) is now recognized as the third "gasotransmitters" and proved to exert a wide range of physiological and cytoprotective functions in the biological systems. Among these functions, the role of H2S in oxidative stress has been one of the main focuses over years. However, the underlying mechanisms for the antioxidant effect of H2S are still poorly comprehended. This review presents an overview of the current understanding of H2S specially focusing on the new understanding and mechanisms of the antioxidant effects of H2S based on recent reports. Both inhibition of ROS generation and stimulation of antioxidants are discussed. H2S-induced S-sulfhydration of key proteins (e.g., p66Shc and Keap1) is also one of the focuses of this review. PMID- 26881035 TI - Novel Perspectives in Redox Biology and Pathophysiology of Failing Myocytes: Modulation of the Intramyocardial Redox Milieu for Therapeutic Interventions-A Review Article from the Working Group of Cardiac Cell Biology, Italian Society of Cardiology. AB - The prevalence of heart failure (HF) is still increasing worldwide, with enormous human, social, and economic costs, in spite of huge efforts in understanding pathogenetic mechanisms and in developing effective therapies that have transformed this syndrome into a chronic disease. Myocardial redox imbalance is a hallmark of this syndrome, since excessive reactive oxygen and nitrogen species can behave as signaling molecules in the pathogenesis of hypertrophy and heart failure, leading to dysregulation of cellular calcium handling, of the contractile machinery, of myocardial energetics and metabolism, and of extracellular matrix deposition. Recently, following new interesting advances in understanding myocardial ROS and RNS signaling pathways, new promising therapeutical approaches with antioxidant properties are being developed, keeping in mind that scavenging ROS and RNS tout court is detrimental as well, since these molecules also play a role in physiological myocardial homeostasis. PMID- 26881037 TI - Exercise Training Improves the Altered Renin-Angiotensin System in the Rostral Ventrolateral Medulla of Hypertensive Rats. AB - The imbalance between angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7) in the brain has been reported to contribute to cardiovascular dysfunction in hypertension. Exercise training (ExT) is beneficial to hypertension and the mechanism is unclear. This study was aimed to determine if ExT improves hypertension via adjusting renin angiotensin system in cardiovascular centers including the rostral ventrolateral medulla (RVLM). Spontaneously hypertensive rats (SHR, 8 weeks old) were subjected to low-intensity ExT or kept sedentary (Sed) for 12 weeks. Blood pressure elevation coupled with increase in age was significantly decreased in SHR received ExT compared with Sed. The results in vivo showed that ExT significantly reduced or increased the cardiovascular responses to central application of sarthran (antagonist of Ang II) or A779 (antagonist of Ang 1-7), respectively. The protein expression of the Ang II acting receptor AT1R and the Ang 1-7 acting receptor Mas in the RVLM was significantly reduced and elevated in SHR following ExT, respectively. Moreover, production of reactive oxygen species in the RVLM was significantly decreased in SHR following ExT. The current data suggest that ExT improves hypertension via improving the balance of Ang II and Ang 1-7 and antioxidative stress at the level of RVLM. PMID- 26881036 TI - Antioxidant Potential of Spirulina platensis Mitigates Oxidative Stress and Reprotoxicity Induced by Sodium Arsenite in Male Rats. AB - The present study aimed to examine the protective role of Spirulina platensis (S. platensis) against arsenic-induced testicular oxidative damage in rats. Arsenic (in the form of NaAsO2 at a dose of 6.3 mg/kg body weight for 8 weeks) caused a significant accumulation of arsenic in testicular tissues as well as a decrease in the levels of testicular superoxide dismutase (SOD), catalase (CAT), reduced glutathione, and zinc. Moreover, it significantly decreased plasma testosterone, luteinizing hormone (LH), triiodothyronine (T3), and thyroxine (T4) levels and reduced sperm motility and sperm count. Arsenic (AS) led to a significant increase in testicular malondialdehyde (MDA), tumour necrosis factor alpha (TNF alpha), nitric oxide (NO), and sperm abnormalities. S. platensis at a dose of 300 mg/kg was found to attenuate As-induced oxidative stress, testicular damage, and sperm abnormalities by its potent antioxidant activity. S. platensis may represent a potential therapeutic option to protect the testicular tissue from arsenic intoxication. PMID- 26881039 TI - Is Modulation of Oxidative Stress an Answer? The State of the Art of Redox Therapeutic Actions in Neurodegenerative Diseases. AB - The central nervous system is particularly sensitive to oxidative stress due to many reasons, including its high oxygen consumption even under basal conditions, high production of reactive oxygen and nitrogen species from specific neurochemical reactions, and the increased deposition of metal ions in the brain with aging. For this reason, along with inflammation, oxidative stress seems to be one of the main inducers of neurodegeneration, causing excitotoxicity, neuronal loss, and axonal damage, ultimately being now considered a key element in the onset and progression of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, and hereditary spastic paraplegia. Thus, the present paper reviews the role of oxidative stress and of its mechanistic insights underlying the pathogenesis of these neurodegenerative diseases, with particular focus on current studies on its modulation as a potential and promising therapeutic strategy. PMID- 26881040 TI - Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation. AB - Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils. PMID- 26881038 TI - Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality? AB - The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements. PMID- 26881041 TI - Liver Damage in Patients with HCV/HIV Coinfection Is Linked to HIV-Related Oxidative Stress. AB - HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage. PMID- 26881042 TI - Proliferation of Human Primary Myoblasts Is Associated with Altered Energy Metabolism in Dependence on Ageing In Vivo and In Vitro. AB - BACKGROUND. Ageing is associated with suppressed regenerative potential of muscle precursor cells due to decrease of satellite cells and suppressive intramuscular milieu on their activation, associated with ageing-related low-grade inflammation. The aim of the study was to characterize the function of oxidative phosphorylation (OXPHOS), glycolysis, adenylate kinase (AK), and creatine kinase (CK) mediated systems in young and older individuals. MATERIALS AND METHODS. Myoblasts were cultivated from biopsies taken by transcutaneous conchotomy from vastus lateralis muscle in young (20-29 yrs, n = 7) and older (70-79 yrs, n = 7) subjects. Energy metabolism was assessed in passages 2 to 6 by oxygraphy and enzyme analysis. RESULTS. In myoblasts of young and older subjects the rate of OXPHOS decreased during proliferation from passages 2 to 6. The total activities of CK and AK decreased. Myoblasts of passage 2 cultivated from young muscle showed higher rate of OXPHOS and activities of CK and AK compared to myoblasts from older subjects while hexokinase and pyruvate kinase were not affected by ageing. CONCLUSIONS. Proliferation of myoblasts in vitro is associated with downregulation of OXPHOS and energy storage and transfer systems. Ageing in vivo exerts an impact on satellite cells which results in altered metabolic profile in favour of the prevalence of glycolytic pathways over mitochondrial OXPHOS of myoblasts. PMID- 26881044 TI - Experimental Colitis Is Attenuated by Cardioprotective Diet Supplementation That Reduces Oxidative Stress, Inflammation, and Mucosal Damage. AB - Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD) are multifactorial, relapsing disorders of the gastrointestinal tract. However, the etiology is still poorly understood but involves altered immune responses, epithelial dysfunction, environmental factors, and nutrition. Recently, we have shown that the diet supplement corabion has cardioprotective effects due to reduction of oxidative stress and inflammation. Since oxidative stress and inflammation are also prominent risk factors in IBD, we speculated that corabion also has beneficial effects on experimental colitis. Colitis was induced in male mice by administration of 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for a period of 3 or 7 days with or without daily gavage feeding of corabion consisting of vitamin C, vitamin E, L-arginine, and eicosapentaenoic and docosahexaenoic acid. We found that corabion administration attenuated DSS-induced colon shortening, tissue damage, and disease activity index during the onset of colitis. Mechanistically, these effects could be explained by reduced neutrophil recruitment, oxidative stress, production of proinflammatory cytokines, and internalization of the junctional proteins ZO-1 and E-cadherin leading to less edema formation. Thus, corabion may be a useful diet supplement for the management of chronic inflammatory intestinal disorders such as IBD. PMID- 26881045 TI - Interplay between Superoxide Dismutase, Glutathione Peroxidase, and Peroxisome Proliferator Activated Receptor Gamma Polymorphisms on the Risk of End-Stage Renal Disease among Han Chinese Patients. AB - Background. Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders. However, little is known regarding the effect of antioxidant SNPs on renal events. Methods. We prospectively enrolled multicenter patients with end-stage renal disease (ESRD) and those without chronic kidney disease (CKD) of Han Chinese origin, with SOD2 (Val16Ala), GPX1 (Pro197Leu), and PPAR-gamma (Pro12Ala, C161T) genotyped. Multiple regression analyses were conducted to evaluate the significant risk determinants for ESRD. Results. Compared to ESRD patients, non-CKD subjects were more likely to have T allele at SOD2 Val16Ala (p = 0.036) and CC genotype at PPAR gamma Pro12Ala (p = 0.028). Regression analysis showed that TT genotype of SOD2 Val16Ala conferred significantly lower ESRD risk among patients without diabetes (odds ratio 0.699; p = 0.018). GPX1 SNP alone did not alter the risk. We detected significant interactions between SNPs including PPAR-gamma Pro12Ala, C161T, and GPX1 regarding the risk of ESRD. Conclusion. This is the first and largest study on the association between adverse renal outcomes and antioxidant SNPs among Han Chinese population. Determination of SOD2 and PPAR-gamma SNPs status might assist in ESRD risk estimation. PMID- 26881043 TI - A Potential Alternative against Neurodegenerative Diseases: Phytodrugs. AB - Neurodegenerative diseases (ND) primarily affect the neurons in the human brain secondary to oxidative stress and neuroinflammation. ND are more common and have a disproportionate impact on countries with longer life expectancies and represent the fourth highest source of overall disease burden in the high-income countries. A large majority of the medicinal plant compounds, such as polyphenols, alkaloids, and terpenes, have therapeutic properties. Polyphenols are the most common active compounds in herbs and vegetables consumed by man. The biological bioactivity of polyphenols against neurodegeneration is mainly due to its antioxidant, anti-inflammatory, and antiamyloidogenic effects. Multiple scientific studies support the use of herbal medicine in the treatment of ND; however, relevant aspects are still pending to explore such as metabolic analysis, pharmacokinetics, and brain bioavailability. PMID- 26881046 TI - Maresin 1, a Proresolving Lipid Mediator, Mitigates Carbon Tetrachloride-Induced Liver Injury in Mice. AB - Maresin 1 (MaR 1) was recently reported to have protective properties in several different animal models of acute inflammation by inhibiting inflammatory response. However, its function in acute liver injury is still unknown. To address this question, we induced liver injury in BALB/c mice with intraperitoneal injection of carbon tetrachloride with or without treatment of MaR 1. Our data showed that MaR 1 attenuated hepatic injury, oxidative stress, and lipid peroxidation induced by carbon tetrachloride, as evidenced by increased thiobarbituric acid reactive substances and reactive oxygen species levels were inhibited by treatment of MaR 1. Furthermore, MaR 1 increased activities of antioxidative mediators in carbon tetrachloride-treated mice liver. MaR 1 decreased indices of inflammatory mediators such as tumor necrosis factor-alpha, interleukin-6, interleukin-1beta, monocyte chemotactic protein 1, myeloperoxidase, cyclooxygenase-2, and inducible nitric oxide synthase. Administration of MaR 1 inhibited activation of nuclear factor kappa B (NF kappab) and mitogen-activated protein kinases (MAPKs) in the liver of CCl4 treated mice. In conclusion, these results suggested the antioxidative, anti inflammatory properties of MaR 1 in CCl4 induced liver injury. The possible mechanism is partly implicated in its abilities to inhibit ROS generation and activation of NF-kappab and MAPK pathway. PMID- 26881047 TI - In Situ Evaluation of Oxidative Stress in Rat Fatty Liver Induced by a Methionine and Choline-Deficient Diet. AB - Nonalcoholic fatty liver disease (NAFLD) is a serious health problem in developed countries. We documented the effects of feeding with a NAFLD-inducing, methionine and choline-deficient (MCD) diet, for 1-4 weeks on rat liver oxidative stress, with respect to a control diet. Glycogen, neutral lipids, ROS, peroxidated proteins, and SOD2 were investigated using histochemical procedures; ATP, GSH, and TBARS concentrations were investigated by biochemical dosages, and SOD2 expression was investigated by Western Blotting. In the 4-week-diet period, glycogen stores decreased whereas lipid droplets, ROS, and peroxidated proteins expression (especially around lipid droplets of hepatocytes) increased. SOD2 immunostaining decreased in poorly steatotic hepatocytes but increased in the thin cytoplasm of macrosteatotic cells; a trend towards a quantitative decrease of SOD expression in homogenates occurred after 3 weeks. ATP and GSH values were significantly lower for rats fed with the MCD diet with respect to the controls. An increase of TBARS in the last period of the diet is in keeping with the high ROS production and low antioxidant defense; these TBARS may promote protein peroxidation around lipid droplets. Since these proteins play key roles in lipid mobilization, storage, and metabolism, this last information appears significant, as it points towards a previously misconsidered target of NAFLD-associated oxidative stress that might be responsible for lipid dysfunction. PMID- 26881048 TI - Effects of Astragalus Polysaccharides on Dysfunction of Mitochondrial Dynamics Induced by Oxidative Stress. AB - This paper studied the chronic fatigue induced by excessive exercise and the restoration effects of Astragalus polysaccharides (APS) on mitochondria. In vivo, we found that excessive exercise could cause oxidative stress statue which led to morphological and functional changes of mitochondria. The changes, including imbalance between mitochondria fusion-fission processes, activation of mitophagy, and decrease of PGC-1alpha expression, could be restored by APS. We further confirmed in vitro, and what is more, we found that APS may ameliorate mitochondrial dysfunction through Sirt1 pathway. Based on the results, we may figure out part of the molecular mechanism of mitochondrial amelioration by APS. PMID- 26881051 TI - Effects of healthy aging on human primary visual cortex. AB - Aging often results in reduced visual acuity from changes in both the eye and neural circuits [1-4]. In normally aging subjects, primary visual cortex has been shown to have reduced responses to visual stimulation [5]. It is not known, however, to what extent aging affects visual field representations and population receptive sizes in human primary visual cortex. Here we use functional MRI (fMRI) and population receptive field (pRF) modeling [6] to measure angular and eccentric retinotopic representations and population receptive fields in primary visual cortex in healthy aging subjects ages 57 - 70 and in healthy young volunteers ages 24 - 36 (n = 9). Retinotopic stimuli consisted of black and white, drifting checkerboards comprising moving bars 11 deg in radius. Primary visual cortex (V1) was clearly identifiable along the calcarine sulcus in all hemispheres. There was a significant decrease in the surface area of V1 from 0 to 3 deg eccentricity in the aging subjects with respect to the young subjects (p = 0.039). The coherence of the fMRI% BOLD modulation was significantly decreased in the aging subjects compared to the young subjects in the more peripheral eccentricity band from 7 to 10 deg (p = 0.029). Finally, pRF sizes were significantly increased within the 0 to 3 deg foveal representation of V1 in the aging subjects compared to the young subjects (p = 0.019). Understanding the extent of changes that occur in primary visual cortex during normal aging is essential both for understanding the normal aging process and for comparisons of healthy, aging subjects with aging patients suffering from age-related visual and cortical disorders. PMID- 26881050 TI - Clinical Implications of Mutations in the PI3K Pathway in HER2+ Breast Cancer: Prognostic or Predictive? AB - Recent advances in tumor genetics and drug development have led to the generation of a wealth of anti-cancer-targeted therapies. These drugs aim at targeting a particular vulnerability in the tumor generated in most cases as a result of dependence on an oncogene and/or loss of a tumor suppressor. Genes in the phosphoinositide 3-kinase (PI3K)/AKT pathway are the most frequently altered in human cancers. Aberrant activation of the PI3K/AKT pathway has been shown to confer resistance to HER2-targeted therapies. Several drugs targeting PI3K/ATK have been developed and are currently in clinical trials in different phases of clinical development, alone or in combination. The impact of mutations in the phosphoinositide 3-kinase (PI3K)/AKT pathway in HER2-amplified breast cancers will be the focus of this review. PMID- 26881052 TI - Prevalence of herbal medicine use and associated factors among pregnant women attending antenatal care at public health facilities in Hossana Town, Southern Ethiopia: facility based cross sectional study. AB - BACKGROUND: The use of herbal medicine has been on increase in many developing and industrialized countries. More pregnant women use herbal remedies to treat pregnancy related problems due to cost-effectiveness of therapy and easy access of these products. We sought to assess the prevalence of herbal medicine use and associated factors among pregnant women attending antenatal clinics of public health facilities. METHODS: Facility based cross sectional study was conducted among 363 pregnant women attending antenatal clinics from May to June 2015 at public health facilities in Hossana town, Hadiya zone, Southern Ethiopia. Pretested structured questionnaire was used to collect data from each study subject. Bivariate logistic regression analysis was used to see significance of association between the outcome and independent variables. Odds ratios at 95 % CI were computed to measure the strength of the association between the outcome and the independent variables. P-value <0.05 was considered as a statistically significant in multivariate analysis. RESULT: Two hundred fifty eight (73.1 %) of pregnant women used herbal medicine during current pregnancy . The herbal medicines commonly taken during current pregnancy were ginger (55.8 %), garlic (69.8 %), eucalyptus (11.6 %), tenaadam (rutachalenssis) (26.4 %), damakesse (ocimumlamiifolium) (22.8 %), feto (3.5 %) and omore (3.1 %). Being students (AOR: (5.68, 95 % CI: (1.53, 21.13), second trimester of pregnancy (AOR: 0.22, 95 % CI: (0.08, 0.76), sufficient knowledge on herbal medicine (AOR: 0.37, 95 % CI: (0.19, 0.79), no formal education (AOR: 4.41, 95 % CI: (1.11, 17.56), primary education (AOR: 4.15, 95 % CI: (1.51, 11.45) and secondary education (AOR: 2.55, 95 % CI: (1.08,6.03) were significantly associated with herbal medicine use. CONCLUSION: The findings of this study showed that herbal medicine use during pregnancy is a common experience. Commonly used herbal medicines during current pregnancy were garlic, ginger, tenaadam, damakasse and eucalyptus. Educational status, occupation, knowledge on herbal medicine and second trimester of pregnancy were the major factors affecting use of herbal medicine. Health education about the effects of herbal medicine on pregnancy should be given during antenatal care sessions and through media. Health care providers, especially those that are involved in antenatal care should aware of evidence regarding potential benefits or harm of herbal medicinal agents when used by pregnant women. PMID- 26881053 TI - Health-related quality of life measurement in asthma and chronic obstructive pulmonary disease: review of the 2009-2014 literature. AB - BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are frequent in the general population. These diseases can worsen the quality of life of people suffering from them, limiting their daily activities and disrupting their sleep at night. Some questionnaires to measure the impact of the diseases on the daily life of patients are available. The measurements of subjective outcomes have become a part of clinical practice, and are used very frequently in clinical trials. Our aim was to describe how data on HRQoL in asthma and COPD are reported in papers published in the medical literature. METHODS: We identified papers on the recent respiratory drugs (chemical, not biological), that reported the HRQoL measurement and that were published from 2009 to April 2014. We planned to describe data about HRQoL, and we had no intention of comparing the degree of efficacy of drugs. RESULTS: The most used questionnaires are the Asthma Quality of Life Questionnaire (AQLQ) and the Saint George's Respiratory Questionnaire (SGRQ). These tools, administered at the baseline and at the end of the study (and interim evaluations in the longer studies) allowed for the identification of improvements as perceived by the patient after the treatment, even if in some cases these improvements were limited and not clinically relevant. Subjective measurements have always been placed among the secondary endpoints and the number of patients (estimated for the main endpoint) has often statistically overestimated the result. In addition, it is clear that subjective data is normally reported, but rarely commented on. CONCLUSIONS: There are some methodology aspects that should be discussed in more depth, for example the necessity to express variations in the subjective perception, not as p-value but as effect-size. PMID- 26881049 TI - Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most prevalent age-related dementia affecting millions of people worldwide. Its main pathological hallmark feature is the formation of insoluble protein deposits of amyloid-beta and hyperphosphorylated tau protein into extracellular plaques and intracellular neurofibrillary tangles, respectively. Many of the mechanistic details of this process remain unknown, but a well-established consequence of protein aggregation is synapse dysfunction and neuronal loss in the AD brain. Different pathways including mitochondrial dysfunction, oxidative stress, inflammation, and metal metabolism have been suggested to be implicated in this process. In particular, a body of evidence suggests that neuronal metal ions such as copper, zinc, and iron play important roles in brain function in health and disease states and altered homeostasis and distribution as a common feature across different neurodegenerative diseases and aging. In this focused review, we overview neuronal proteins that are involved in AD and whose metal binding properties may underlie important biochemical and regulatory processes occurring in the brain during the AD pathophysiological process. PMID- 26881054 TI - Gene expression in the brain of a migratory songbird during breeding and migration. AB - BACKGROUND: We still have limited knowledge about the underlying genetic mechanisms that enable migrating species of birds to navigate the globe. Here we make an attempt to get insight into the genetic architecture controlling this complex innate behaviour. We contrast the gene expression profiles of two closely related songbird subspecies with divergent migratory phenotypes. In addition to comparing differences in migratory strategy we include a temporal component and contrast patterns between breeding adults and autumn migrating juvenile birds of both subspecies. The two willow warbler subspecies, Phylloscopus trochilus trochilus and P. t. acredula, are remarkably similar both in phenotype and genotype and have a narrow contact zone in central Scandinavia. Here we used a microarray gene chip representing 23,136 expressed sequence tags (ESTs) from the zebra finch Taeniopygia guttata to identify mRNA level differences in willow warbler brain tissue in relation to subspecies and season. RESULTS: Out of the 22,109 EST probe sets that remained after filtering poorly binding probes, we found 11,898 (51.8 %) probe sets that could be reliably and uniquely matched to a total of 6,758 orthologous zebra finch genes. The two subspecies showed very similar levels of gene expression with less than 0.1 % of the probe sets being significantly differentially expressed. In contrast, 3,045 (13.8 %) probe sets were found to be differently regulated between samples collected from breeding adults and autumn migrating juvenile birds. The genes found to be differentially expressed between seasons appeared to be enriched for functional roles in neuronal firing and neuronal synapse formation. CONCLUSIONS: Our results show that only few genes are differentially expressed between the subspecies. This suggests that the different migration strategies of the subspecies might be governed by few genes, or that the expression patterns of those genes are time structured or tissue-specific in ways, which our approach fails to uncover. Our findings will be useful in the planning of new experiments designed to unravel the genes involved in the migratory program of birds. PMID- 26881055 TI - Assessment of the nevirapine safety signal using data from the national antiretroviral dispensing database: a retrospective study. AB - BACKGROUND: Clinical trials showed a higher risk of skin- and liver- related adverse reactions when NVP-based antiretroviral therapy (ART) was initiated in female and male patients with baseline CD4 cell counts >=250 and >=400, respectively. Some studies reported no difference in risk between the high and low CD4 count groups. Consequently, the use of NVP-based ART in all patients with a CD4 cell count <350, was recommended. In 2011, the Pharmacovigilance Centre detected an increase in reports of grade III and IV reactions. The center was required to determine if there was an increase in NVP-related reactions. METHODS: Automated dispensing records from January 2008 to November 2011 were accessed from the National Antiretroviral Dispensing Database (NDB). Records of patients who were initiated on NVP-based ART were selected, and records showing a replacement of NVP with protease inhibitor (PI) were identified. The proportions of grade III and IV reactions were calculated per quarter, and Odds Ratios (OR) were calculated, with the confidence interval set at 95 % and a p-value of <0.05. RESULTS: From 2008 to 2011 a total of 84,741 patients were started on ART. Of these 67,794 were initiated on NVP-containing ART. Of these, 211 females and 79 males were substituted from NVP to a PI. The OR for females was 2.4 (95 % confidence interval [CI] 1.8 - 3.1). For males the OR was 2.4 (OR 2.4; 95 % CI 1.4 - 3.8) which occurred nine months after the change observed in the females. The odds of a NVP-to-PI substitution in females compared to males before the launch of Namibia's 2010 ART guidelines was the same as the odds after the publication of the guidelines (before, OR 1.6; 95 % CI 1.1 - 2.5; after, OR 1.6; 95 % CI 1.2 - 2.2). CONCLUSIONS: There was an increase in substitutions of NVP with a PI following the increase in the CD4 threshold for initiating NVP-based HAART, meaning that there was an increase in grade III and IV reactions associated with NVP. Therefore the NVP-safety signal was confirmed to be a true signal, which contributed to the Ministry's decision to review the use of NVP. PMID- 26881056 TI - Comparison of Partec Rapid Malaria Test with Conventional Light Microscopy for Diagnosis of Malaria in Northwest Ethiopia. AB - Background. Laboratory diagnosis of malaria is the key for effective disease management. Diagnosis of malaria infection requires rapid, sensitive, and specific test methods with an affordable cost. This study was aimed to assess the diagnostic performance of Partec rapid malaria test with reference to light microscopy for the diagnosis of malaria in Northwest Ethiopia. Methods. A total of 180 febrile patients were tested for malaria using Giemsa stain microscopy and Partec rapid malaria test from June to July 2013 at Gendewuha health centers, Metema district. Data were analyzed using SPSS version 20 statistical software. Odds ratio with 95% CI was calculated. Result. The sensitivity and specificity of Partec rapid malaria test were 93.8% (95% CI = 87.1%-100%) and 87.9% (95% CI = 79.7%-96.1%), respectively, while the positive predictive value and negative predictive value were 6.4% (95% CI = 77.2%-95.5%) and 94.6% (95% CI = 88.7% 100%), respectively. There was also an excellent agreement between two tests with Kappa value of 0.811 (95% CI = 0.625-0.996). Conclusion. Partec rapid malaria test showed good sensitivity and specificity with an excellent agreement to the reference light microscopy. Therefore PT can be considered as alternative diagnostic tools in malaria endemic areas. PMID- 26881057 TI - Pathogenesis of Common Ocular Diseases. PMID- 26881058 TI - Novice Reviewers Retain High Sensitivity and Specificity of Posterior Segment Disease Identification with iWellnessExamTM. AB - Introduction. Four novices to Spectral Domain Optical Coherence Tomography (SD OCT) image review were provided a brief lecture on the interpretation of iVue iWellnessExamTM findings (available on iVue(r) SD-OCT, Optovue, Inc., Fremont, CA). For a cohort of 126 (Confirmed) Normal, 101 (Confirmed) Disease subjects, iWellnessExamTM OD, OS, and OU reports were provided. Each novice independently reviewed and sorted the subjects into one of four categories: normal, retinal disease, optic nerve (ON) disease, and retinal + ON disease. Their accuracy is compared between the novices and with an expert reviewer. Results. Posterior segment disease was properly detected by novices with sensitivities of 90.6%, any disease; 84.3%, retinal disease; 88.0%, ON disease; expert sensitivity: 96.0%, 95.5%, and 90.0%, respectively; specificity: 84.3%, novices; 99.2%, expert. Novice accuracy correlates best with clinical exposure and amount of time spent reviewing each image set. The novices' negative predictive value was 92.0% (i.e., very few false negatives). Conclusions. Novices can be trained to screen for posterior segment disease efficiently and effectively using iWellnessExamTM data, with high sensitivity, while maintaining high specificity. Novice reviewer accuracy covaries with both clinical exposure and time spent per image set. These findings support exploration of training nonophthalmic technicians in a primary medical care setting. PMID- 26881059 TI - Evaluation of Dry Eye and Meibomian Gland Dysfunction in Teenagers with Myopia through Noninvasive Keratograph. AB - Purpose. This study aims to evaluate dry eye and ocular surface conditions of myopic teenagers by using questionnaire and clinical examinations. Methods. A total of 496 eyes from 248 myopic teenagers (7-18 years old) were studied. We administered Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp examination, and Keratograph 5M. The patients were divided into 2 groups based on OSDI dry eye standard, and their ocular surfaces and meibomian gland conditions were evaluated. Results. The tear meniscus heights of the dry eye and normal groups were in normal range. Corneal fluorescein scores were significantly higher whereas noninvasive break-up time was dramatically shorter in the dry eye group than in the normal group. All three meibomian gland dysfunction parameters (i.e., meibomian gland orifice scores, meibomian gland secretion scores, and meibomian gland dropout scores) of the dry eye group were significantly higher than those of the normal group (P < 0.0001). Conclusions. The prevalence of dry eye in myopic teenagers is 18.95%. Meibomian gland dysfunction plays an important role in dry eye in myopic teenagers. The Keratograph 5M appears to provide an effective noninvasive method for assessing ocular surface situation of myopic teenagers. PMID- 26881060 TI - Usefulness of Surgical Media Center as a Cataract Surgery Educational Tool. AB - Purpose. This study retrospectively analyzed cataract surgeries to examine the usefulness of Surgical Media Center (SMC) (Abbott Medical Optics Inc.), a new cataract surgery recording device, for training of cataract surgery. Methods. We studied five hundred cataract surgeries conducted with a phacoemulsification system connected to the SMC. After surgery, the surgical procedures were reviewed, with changes in aspiration rate, vacuum level, and phaco power displayed as graphs superimposed on the surgical video. We examined whether use of SMC is able to demonstrate the differences in technique between experienced and trainee operators, to identify inappropriate phacoemulsification techniques from analyzing the graphs, and to elucidate the cause of intraoperative complications. Results. Significant differences in the time taken to reach maximum vacuum and the speed of increase in vacuum during irrigation and aspiration were observed between experienced and trainee operators. Analysis of the graphs displayed by SMC detected inappropriate phacoemulsification techniques mostly in cases operated by trainee operators. Conclusions. Using SMC, it was possible to capture details of cataract surgery objectively. This recording device allows surgeons to review cataract surgery techniques and identify the cause of intraoperative complication and is a useful education tool for cataract surgery. PMID- 26881061 TI - Scheimpflug Imaging Parameters Associated with Tear Mediators and Bronchial Asthma in Keratoconus. AB - Purpose. To determine associations between mediators in tears in the whole spectrum of keratoconus (KC); to explore connections between mediators and Scheimpflug parameters; to examine correlations between Scheimpflug parameters and bronchial asthma. Methods. Tear samples were collected from 69 patients and 19 controls. Concentrations of mediators-IL-6, -10; CXCL8, CCL5; MMP-9, -13; TIMP 1; t-PA, PAI-1-were measured by Cytometric Bead Array. Measured Pentacam parameters include keratometry values (K 1, K 2, K max), corneal thickness (Pachy Pupil, Apex, Min), and elevations and indices (including Belin-Ambrosio deviation (BAD-D)). Results. A number of significant positive associations were observed between pairs of mediator concentrations. Significant positive correlations were found between BAD-D and CXCL8/MMP-9 and K 2 and MMP-9. Significant negative associations were explored between Pachy Min and CXCL8/t-PA. Significant associations were found between pairs of mediators (IL-6 and CXCL8; CCL5 and CXCL8/MMP-9; TIMP-1 and MMP-9/-13/t-PA; t-PA and CXCL8/CCL5/PAI-1) and the severity of KC. Significant positive correlation between asthma and the severity of KC was explored. Conclusion. Cooperation of different mediators in tears all taking part in the complex pathomechanism of keratoconus was revealed. Our research verifies that inflammation plays a crucial role in the pathogenesis of KC. Additionally this study confirms the effect of bronchial asthma on keratoconus. PMID- 26881062 TI - Endotoxin-Induced Tryptophan Degradation along the Kynurenine Pathway: The Role of Indolamine 2,3-Dioxygenase and Aryl Hydrocarbon Receptor-Mediated Immunosuppressive Effects in Endotoxin Tolerance and Cancer and Its Implications for Immunoparalysis. AB - The degradation of tryptophan (TRP) along the kynurenine pathway plays a crucial role as a neuro- and immunomodulatory mechanism in response to inflammatory stimuli, such as lipopolysaccharides (LPS). In endotoxemia or sepsis, an enhanced activation of the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO) is associated with a higher mortality risk. It is assumed that IDO induced immunosuppressive effects provoke the development of a protracted compensatory hypoinflammatory phase up to a complete paralysis of the immune system, which is characterized by an endotoxin tolerance. However, the role of IDO activation in the development of life-threatening immunoparalysis is still poorly understood. Recent reports described the impact of inflammatory IDO activation and aryl hydrocarbon receptor- (AhR-) mediated pathways on the development of LPS tolerance and immune escape of cancer cells. These immunosuppressive mechanisms offer new insights for a better understanding of the development of cellular dysfunctions in immunoparalysis. This review provides a comprehensive update of significant biological functions of TRP metabolites along the kynurenine pathway and the complex regulation of LPS-induced IDO activation. In addition, the review focuses on the role of IDO-AhR-mediated immunosuppressive pathways in endotoxin tolerance and carcinogenesis revealing the significance of enhanced IDO activity for the establishment of life-threatening immunoparalysis in sepsis. PMID- 26881064 TI - A Systematic Review and Meta-Analysis on the Association between Hypertension and Tinnitus. AB - Hypertension has been suggested to be one possible risk factor of tinnitus, but the association between hypertension and tinnitus remains uncertain. The authors performed a meta-analysis of the existing studies on the association between hypertension and tinnitus. We performed literature search of studies using SinoMed, CNKI, WanFang, PubMed, Scopus, Web of Science, and Google Scholar. Studies reported the odds ratio and 95% confidence interval (CI) (or provided sufficient information for calculation) of the association between hypertension and tinnitus were included. A total of 19 eligible studies with 20 effect estimates were used in this study. They included 63,154 participants with age ranging from 14 to 92. The pooled OR, which was pooled using a random effects model, was 1.37 (95% CI: 1.16 to 1.62). There was no evidence of publication bias (p = 0.11 for Begg's test, p = 0.96 for Egger's test). By meta-regression, we found that study design may be one possible factor of heterogeneity. Sensitivity analysis found that the result was stable. This study suggests that hypertension might be one risk factor of tinnitus, and hypertension prevention and control might be helpful in preventing tinnitus. PMID- 26881063 TI - Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. AB - L-Tryptophan is the unique protein amino acid (AA) bearing an indole ring: its biotransformation in living organisms contributes either to keeping this chemical group in cells and tissues or to breaking it, by generating in both cases a variety of bioactive molecules. Investigations on the biology of Trp highlight the pleiotropic effects of its small derivatives on homeostasis processes. In addition to protein turn-over, in humans the pathways of Trp indole derivatives cover the synthesis of the neurotransmitter/hormone serotonin (5-HT), the pineal gland melatonin (MLT), and the trace amine tryptamine. The breakdown of the Trp indole ring defines instead the "kynurenine shunt" which produces cell-response adapters as L-kynurenine, kynurenic and quinolinic acids, or the coenzyme nicotinamide adenine dinucleotide (NAD(+)). This review aims therefore at tracing a "map" of the main molecular effectors in human tryptophan (Trp) research, starting from the chemistry of this AA, dealing then with its biosphere distribution and nutritional value for humans, also focusing on some proteins responsible for its tissue-dependent uptake and biotransformation. We will thus underscore the role of Trp biochemistry in the pathogenesis of human complex diseases/syndromes primarily involving the gut, neuroimmunoendocrine/stress responses, and the CNS, supporting the use of -Omics approaches in this field. PMID- 26881066 TI - Production of Thermoalkaliphilic Lipase from Geobacillus thermoleovorans DA2 and Application in Leather Industry. AB - Thermophilic and alkaliphilic lipases are meeting a growing global attention as their increased importance in several industrial fields. Over 23 bacterial strains, novel strain with high lipolytic activity was isolated from Southern Sinai, Egypt, and it was identified as Geobacillus thermoleovorans DA2 using 16S rRNA as well as morphological and biochemical features. The lipase was produced in presence of fatty restaurant wastes as an inducing substrate. The optimized conditions for lipase production were recorded to be temperature 60 degrees C, pH 10, and incubation time for 48 hrs. Enzymatic production increased when the organism was grown in a medium containing galactose as carbon source and ammonium phosphate as nitrogen source at concentrations of 1 and 0.5% (w/v), respectively. Moreover, the optimum conditions for lipase production such as substrate concentration, inoculum size, and agitation rate were found to be 10% (w/v), 4% (v/v), and 120 rpm, respectively. The TA lipase with Triton X-100 had the best degreasing agent by lowering the total lipid content to 2.6% as compared to kerosene (7.5%) or the sole crude enzyme (8.9%). It can be concluded that the chemical leather process can be substituted with TA lipase for boosting the quality of leather and reducing the environmental hazards. PMID- 26881065 TI - Immunomodulatory Effects of Chitotriosidase Enzyme. AB - Chitotriosidase enzyme (EC: 3.2.1.14) is the major active chitinase in the human body. It is produced mainly by activated macrophages, in which its expression is regulated by multiple intrinsic and extrinsic signals. Chitotriosidase was confirmed as essential element in the innate immunity against chitin containing organisms such as fungi and protozoa; however, its immunomodulatory effects extend far beyond innate immunity. In the current review, we will try to explore the expanding spectrum of immunological roles played by chitotriosidase enzyme in human health and disease and will discuss its up-to-date clinical value. PMID- 26881068 TI - Spectrum of Intracerebral Hemorrhage in Children: A Report from PICU of a Resource Limited Country. AB - Intracerebral hemorrhage (ICH) in children is a rare but disabling disease that accounts for almost half cases of stroke. We report our experience of ICH in children. Retrospective review of medical records of children (1 month-16 years) admitted in Pediatric Intensive Care Unit between January 2007 and December 2014 was done. Data collected included age, gender, presentation, examination findings, neuroimaging done (CT, MRI, and angiography) management (conservative/intervention), and outcome. Results are presented as frequency and percentages. Of the total 50 patients, 58% were male and 26% were <1 year. On presentation 44% had vomiting, 42% had seizures, and GCS < 8 while 40% had altered level of consciousness. Single bleed was present in 88%, 94% had supratentorial bleed, and 32% had intraventricular extension. 72% had bleed volume of <30 mL and 8% had >60 mL. CT scan was done in 98% patients and MRI in 34%, while 6% underwent conventional angiography. 60% patients were managed conservatively, 36% underwent neurosurgical intervention, and 6% underwent radiological vascular intervention. Hematologic causes were identified in 52% patients and vascular malformations in 14% and in 26% no cause could be identified. 26% of patients expired. PMID- 26881067 TI - A Copy Number Variant on Chromosome 20q13.3 Implicated in Thinness and Severe Obesity. AB - BACKGROUND/OBJECTIVES: To identify copy number variants (CNVs) which are associated with body mass index (BMI). SUBJECTS/METHODS: CNVs were identified using array comparative genomic hybridization (aCGH) on members of pedigrees ascertained through severely obese (BMI >= 35 kg/m(2)) sib pairs (86 pedigrees) and thin (BMI <= 23 kg/m(2)) probands (3 pedigrees). Association was inferred through pleiotropy of BMI with CNV log?2 intensity ratio. RESULTS: A 77-kilobase CNV on chromosome 20q13.3, confirmed by real-time qPCR, exhibited deletions in the obese subjects and duplications in the thin subjects (P = 2.2 * 10(-6)). Further support for the presence of a deletion derived from inference by likelihood analysis of null alleles for SNPs residing in the region. CONCLUSIONS: One or more of 7 genes residing in a chromosome 20q13.3 CNV region appears to influence BMI. The strongest candidate is ARFRP1, which affects glucose metabolism in mice. PMID- 26881070 TI - The Relationship between Self-Efficacy and Psychosocial Care in Adolescents with Epilepsy. AB - Introduction. Studies about epilepsy are more associated with physiological aspects and drug therapy and far too little attention has been paid to psychological and social care, especially in teens. Hence, the present study aimed to assess relationship between self-efficacy and psychosocial care in adolescents with epilepsy. Methods. A cross-sectional association study was conducted on 74 consecutive adolescents aged 10 to 18 years with general attacks of epilepsy referred to Pediatric Neurology Clinics affiliated with the Tabriz University of Medical Sciences in 2013. Data were collected by interview using multisegment tools including demographic characteristics, self-efficacy scaling in children with epilepsy, and reporting tools for children psychosocial care. Results. Our study showed a significant association of self-efficacy with "information received" (P < 0.02) and also with "need for information or support" (P < 0.01) as well as "concerns and fears" (P < 0.01). The comments of doctor or nurse were directly associated with higher self-efficacy and patients' information needs were inversely associated with higher self-efficacy. Conclusion. For adolescents with epilepsy, providing educational materials such as pamphlets and booklets, designing especial websites, and setting especial meetings with and without parents separately are recommended. Scheduling psychosocial supports and collecting more information about this disorder for adolescents will be helpful. PMID- 26881069 TI - Efficacy of Electroconvulsive Therapy in Bipolar Disorder with Mixed Features. AB - Introduction. Mixed states represent a frequent presentation of bipolar disorder, associated with higher resistance to psychopharmacology. Limited evidence supports the use of ECT in these patients. We aim to report our experience on treating bipolar mixed states with ECT. Methods. Retrospective data were collected from all bipolar patients submitted to acute ECT treatment, between June 2006 and June 2011. Three groups were created in terms of affective polarity of the episode. CGI rating was used to establish clinical remission and demographic and clinical variables were compared among groups. Long-term outcome was assessed through readmission measures, considering the use of continuation or maintenance ECT. Results. During the study time frame, a total of 50 ECT course treatments were performed on 41 bipolar patients. All affective episodes, except one mixed state, showed a positive clinical response. Patients with mixed state presentation tended to be younger and have an earlier first hospitalization than depressed patients. No differences were found in terms of ECT sessions performed, length of hospital admission, referral to continuation ECT treatment, number of readmissions, and time until next readmission. Conclusions. Our results support the effectiveness of ECT in patients experiencing a mixed affective state. PMID- 26881071 TI - Length of Stay Comparison between Rivaroxaban and Warfarin in the Treatment of Pulmonary Embolism: Results from a Real-World Observational Cohort Study. AB - Background. Trials have shown that novel oral anticoagulants may decrease length of stay versus warfarin. A comparison of length of stay in the treatment of pulmonary embolism (PE) has not been performed outside post hoc analysis of a large clinical trial. Objective. To evaluate if rivaroxaban decreases length of stay compared to warfarin plus enoxaparin in the treatment of PE. Methods. This was a multicenter, retrospective, observational cohort study. Patients were identified based on discharge diagnosis of PE and were excluded if they received anticoagulants prior to admission and had additional indications for anticoagulation or reduced creatinine clearance. The primary endpoint was length of stay. Secondary endpoints included time from initial dose of oral anticoagulant to discharge and length of stay comparison between subgroups. Results. Inclusion criterion was met by 158 patients (82 warfarin, 76 rivaroxaban). The median length of stay was 4.5 days (interquartile range [IQR], 2.7, 5.9) in the warfarin group and 1.8 days (IQR, 1.2, 3.7) in the rivaroxaban group (P < 0.001). Time interval from first dose of oral anticoagulant to discharge was shorter with rivaroxaban (P < 0.001). Conclusions. Patients given rivaroxaban had decreased length of stay versus those given warfarin plus enoxaparin for the treatment of PE. PMID- 26881072 TI - Factors Associated with Opioid Use in a Cohort of Patients Presenting for Surgery. AB - Objectives. Patients taking opioids prior to surgery experience prolonged postoperative opioid use, worse clinical outcomes, increased pain, and more postoperative complications. We aimed to compare preoperative opioid users to their opioid naive counterparts to identify differences in baseline characteristics. Methods. 107 patients presenting for thoracotomy, total knee replacement, total hip replacement, radical mastectomy, and lumpectomy were investigated in a cross-sectional study to characterize the associations between measures of pain, substance use, abuse, addiction, sleep, and psychological measures (depressive symptoms, Posttraumatic Stress Disorder symptoms, somatic fear and anxiety, and fear of pain) with opioid use. Results. Every 9-point increase in the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R) score was associated with 2.37 (95% CI 1.29-4.32) increased odds of preoperative opioid use (p = 0.0005). The SOAPP-R score was also associated with 3.02 (95% CI 1.36-6.70) increased odds of illicit preoperative opioid use (p = 0.007). Also, every 4-point increase in baseline pain at the future surgical site was associated with 2.85 (95% CI 1.12-7.27) increased odds of legitimate preoperative opioid use (p = 0.03). Discussion. Patients presenting with preoperative opioid use have higher SOAPP-R scores potentially indicating an increased risk for opioid misuse after surgery. In addition, legitimate preoperative opioid use is associated with preexisting pain. PMID- 26881073 TI - Study of Exhaled Nitric Oxide in Subjects with Suspected Obstructive Sleep Apnea: A Pilot Study in Vietnam. AB - BACKGROUND AND OBJECTIVE: The concentration of exhaled nitric oxide (eNO), reflecting the activity of inducible NO synthase in airway epithelium, has been found to increase in patients with obstructive sleep apnea (OSA). This study aimed to measure eNO concentration in patients with suspected OSA and to correlate different eNO parameters with clinical and sleep apnea characteristics. METHODS: In this cross-sectional study, all patients underwent in-lab overnight polysomnography (PSG) and eNO measurement using a method of multiple flow rates before and after PSG (pre- and post-PSG). RESULTS: According to the result of PSG, 82 persons were divided into two groups: control subjects (n = 30; 54 +/- 14 years) and patients with OSA defined as apnea-hypopnea index (AHI) >= 5/hour (n = 52; 53 +/- 12 years). Body mass index (BMI) and neck and abdomen circumferences of OSA patients were significantly higher than those from control subjects. In OSA group, post-PSG alveolar NO concentration (CANO) (5.3 +/- 1.9 ppb) was significantly higher than pre-PSG CANO (4.0 +/- 1.7 ppb; P < 0.001). Significant correlations have been found between CANO and AHI (P < 0.001) and between CANO and nadir SpO2 (P < 0.05). The daytime CANO value of more than 4.1 ppb can be used to screen symptomatic subjects for the presence of OSA with a high specificity of 93.3%. CONCLUSION: Our findings indicate CANO as a surrogate marker for OSA in persons with suggestive symptoms. PMID- 26881075 TI - Synthesis and Anti-Inflammatory Activity of Some O-Propargylated-N-acetylpyrazole Derived from 1,3-Diarylpropenones. AB - In search of novel effective potent therapeutic agents delivered by oral route for inflammation treatment, some novel O-propargylated-N-acetylpyrazole analogs (5a-j) were prepared by treating N-acetylpyrazole (4a-j) derived from 1,3 diarylpropenones (3a-j) with propargyl bromide. Claisen-Schmidt condensation of a series of substituted aryl ketones 1 and benzaldehydes 2 in glacial acetic acid afforded 1,3-diarylpropenones which on further treatment with hydrazine hydrate in acetic acid under reflux conditions afforded 1-acetyl-3,5-diaryl-4,5 dihydro(1H)pyrazoles (4a-j). The products were characterized by using spectroscopic techniques such as IR and NMR. In addition, the in vivo anti inflammatory activity of the synthesized compounds was determined using the carrageenan-induced paw oedema method in rats. PMID- 26881074 TI - Theory of Mind Indexes the Broader Autism Phenotype in Siblings of Children with Autism at School Age. AB - Subclinical variants of the social-communicative challenges and rigidity that define autism spectrum disorder (ASD) are known as the broader autism phenotype (BAP). The BAP has been conceptualized categorically (as specific to a subset of relatives of individuals with ASD) and dimensionally (as continuously distributed within the general population). The current study examined the compatibility of these two approaches by assessing associations among autism symptoms and social communicative skills in young school-age children with ASD, children who have a sibling with ASD, and children without a sibling with ASD. Autism symptoms were associated with reduced Theory of Mind (ToM), adaptive skills, cognitive empathy, and language skills across the full sample. Reduced ToM was a core aspect of the BAP in the current sample regardless of whether the BAP was defined categorically (in terms of siblings of children with ASD who exhibited atypical developmental) or dimensionally (in terms of associations with autism symptoms across the entire sample). Early language skills predicted school-age ToM. Findings support the compatibility of categorical and dimensional approaches to the BAP, highlight reduced ToM as a core aspect of the school-age BAP, and suggest that narrative based approaches to promoting ToM may be beneficial for siblings of children with ASD. PMID- 26881077 TI - Unravelling the Interactions between Hydrolytic and Oxidative Enzymes in Degradation of Lignocellulosic Biomass by Sporothrix carnis under Various Fermentation Conditions. AB - The mechanism underlying the action of lignocellulolytic enzymes in biodegradation of lignocellulosic biomass remains unclear; hence, it is crucial to investigate enzymatic interactions involved in the process. In this study, degradation of corn cob by Sporothrix carnis and involvement of lignocellulolytic enzymes in biodegradation were investigated over 240 h cultivation period. About 60% degradation of corn cob was achieved by S. carnis at the end of fermentation. The yields of hydrolytic enzymes, cellulase and xylanase, were higher than oxidative enzymes, laccase and peroxidase, over 144 h fermentation period. Maximum yields of cellulase (854.4 U/mg) and xylanase (789.6 U/mg) were at 96 and 144 h, respectively. Laccase and peroxidase were produced cooperatively with maximum yields of 489.06 U/mg and 585.39 U/mg at 144 h. Drastic decline in production of cellulase at 144 h (242.01 U/mg) and xylanase at 192 h (192.2 U/mg) indicates that they play initial roles in biodegradation of lignocellulosic biomass while laccase and peroxidase play later roles. Optimal degradation of corn cob (76.6%) and production of hydrolytic and oxidative enzymes were achieved with 2.5% inoculum at pH 6.0. Results suggest synergy in interactions between the hydrolytic and oxidative enzymes which can be optimized for improved biodegradation. PMID- 26881076 TI - Label-Free Proteomic Analysis of Flavohemoglobin Deleted Strain of Saccharomyces cerevisiae. AB - Yeast flavohemoglobin, YHb, encoded by the nuclear gene YHB1, has been implicated in the nitrosative stress responses in Saccharomyces cerevisiae. It is still unclear how S. cerevisiae can withstand this NO level in the absence of flavohemoglobin. To better understand the physiological function of flavohemoglobin in yeast, in the present study a label-free differential proteomics study has been carried out in wild-type and YHB1 deleted strains of S. cerevisiae grown under fermentative conditions. From the analysis, 417 proteins in Y190 and 392 proteins in DeltaYHB1 were identified with high confidence. Interestingly, among the differentially expressed identified proteins, 40 proteins were found to be downregulated whereas 41 were found to be upregulated in DeltaYHB1 strain of S. cerevisiae (p value < 0.05). The differentially expressed proteins were also classified according to gene ontology (GO) terms. The most enriched and significant GO terms included nitrogen compound biosynthesis, amino acid biosynthesis, translational regulation, and protein folding. Interactions of differentially expressed proteins were generated using Search Tool for the Retrieval of Interacting Genes (STRING) database. This is the first report which offers a more complete view of the proteome changes in S. cerevisiae in the absence of flavohemoglobin. PMID- 26881078 TI - Silica Nanoparticles Effects on Blood Coagulation Proteins and Platelets. AB - Interaction of nanoparticles with the blood coagulation is important prior to their using as the drug carriers or therapeutic agents. The aim of present work was studying of the primary effects of silica nanoparticles (SiNPs) on haemostasis in vitro. We studied the effect of SiNPs on blood coagulation directly estimating the activation of prothrombin and factor X and to verify any possible effect of SiNPs on human platelets. It was shown that SiNPs shortened coagulation time in APTT and PT tests and increased the activation of factor X induced by RVV possibly due to the sorption of intrinsic pathway factors on their surface. SiNPs inhibited the aggregation of platelet rich plasma induced by ADP but in the same time partially activated platelets as it was shown using flow cytometry. The possibility of SiNPs usage in nanomedicine is strongly dependant on their final concentration in bloodstream and the size of the particles that are used. However SiNPs are extremely promising as the haemostatic agents for preventing the blood loss after damage. PMID- 26881079 TI - Can Melatonin Act as an Antioxidant in Hydrogen Peroxide-Induced Oxidative Stress Model in Human Peripheral Blood Mononuclear Cells? AB - Purpose. We aimed to investigate the possible effects of melatonin on gene expressions and activities of MnSOD and catalase under conditions of oxidative stress induced by hydrogen peroxide (H2O2) in peripheral blood mononuclear cells (PBMCs). Materials and Methods. PBMCs were isolated from healthy subjects and treated as follows: (1) control (only with 0.1% DMSO for 12 h); (2) melatonin (1 mM) for 12 h; (3) H2O2 (250 MUM) for 2 h; (4) H2O2 (250 MUM) for 2 h following 10 h pretreatment with melatonin (1 mM). The gene expression was evaluated by real time PCR. MnSOD and catalase activities in PBMCs were determined by colorimetric assays. Results. Pretreatment of PBMCs with melatonin significantly augmented expression and activity of MnSOD which were diminished by H2O2. Melatonin treatment of PBMCs caused a significant upregulation of catalase by almost 2-fold in comparison with untreated cells. However, activity and expression of catalase increased by 1.5-fold in PBMCs under H2O2-induced oxidative stress compared with untreated cell. Moreover, pretreatment of PBMCs with melatonin resulted in a significant 1.8-fold increase in catalase expression compared to PBMCs treated only with H2O2. Conclusion. It seems that melatonin could prevent from undesirable impacts of H2O2-induced oxidative stress on MnSOD downregulation. Moreover, melatonin could promote inductive effect of H2O2 on catalase mRNA expression. PMID- 26881080 TI - Australian Pregnant Women's Awareness of Gestational Weight Gain and Dietary Guidelines: Opportunity for Action. AB - BACKGROUND: Excessive gestational weight gain (GWG) can negatively impact on maternal and foetal health. Guidelines based on Institute of Medicine (IOM) encourage managing GWG by following healthy eating recommendations and increasing physical activity. This study investigated pregnant women's knowledge of their optimal GWG and recommended dietary approaches for GWG management. METHOD: English-speaking pregnant women were recruited from five hospitals in New South Wales (Australia) and an online link. Prepregnancy Body Mass Index (BMI) was calculated from self-reported height and prepregnancy weight. Participants identified their recommended GWG. A survey assessed practical dietary knowledge and asked about broad dietary recommendations to prevent excessive GWG. Chi square and logistic regression analyses were used. RESULTS: N = 326 pregnant women completed the surveys; 49% entered pregnancy overweight (25.2%) or obese (23.6%); and knowledge of recommended GWG was lacking. Prepregnancy BMI was a significant predictor of GWG recommendation knowledge (P < 0.000). Pregnant women were highly knowledgeable about broad dietary recommendations but had poor knowledge of detailed recommendations. CONCLUSIONS: Limited knowledge of IOM's GWG guidelines and of specific dietary recommendations for pregnancy should be addressed by health care providers and education initiatives to assist the high number of women who enter pregnancy overweight or obese. PMID- 26881081 TI - Childhood Obesity Associates Haemodynamic and Vascular Changes That Result in Increased Central Aortic Pressure with Augmented Incident and Reflected Wave Components, without Changes in Peripheral Amplification. AB - The aims were to determine if childhood obesity is associated with increased central aortic blood pressure (BP) and to characterize haemodynamic and vascular changes associated with BP changes in obese children and adolescents by means of analyzing changes in cardiac output (stroke volume, SV), arterial stiffness (aortic pulse wave velocity, PWV), peripheral vascular resistances (PVR), and net and relative contributions of reflected waves to the aortic pulse wave amplitude. We included 117 subjects (mean/range age: 10 (5-15) years, 49 females), who were obese (OB) or had normal weight (NW). Peripheral and central aortic BP, PWV, and pulse wave-derived parameters (augmentation index, amplitude of forward and backward components) were measured with tonometry (SphygmoCor) and oscillometry (Mobil-O-Graph). With independence of the presence of dyslipidemia, hypertension, or sedentarism, the aortic systolic and pulse BP were higher in OB than in NW subjects. The increase in central BP could not be explained by the elevation in the relative contribution of reflections to the aortic pressure wave and higher PVR or by an augmented peripheral reflection coefficient. Instead, the rise in central BP could be explained by an increase in the amplitude of both incident and reflect wave components associated to augmented SV and/or PWV. PMID- 26881082 TI - Susceptibility Pattern and Distribution of Oxacillinases and bla PER-1 Genes among Multidrug Resistant Acinetobacter baumannii in a Teaching Hospital in Iran. AB - Acinetobacter baumannii (A. baumannii) is an important nosocomial pathogen in healthcare institutions. beta-Lactamase-mediated resistance is the most common mechanism for carbapenem resistance in A. baumannii. The aim of this study was to determine the antibiotic resistance pattern, to detect OXA encoding genes, class A, bla PER-1, and to detect the presence of ISAba1. A total of 124 A. baumannii isolates were collected from hospitalized patients in a teaching hospital in Kashan, Iran. The susceptibility of isolates to different antibiotics was determined by disk-diffusion method. PCR was used to detect bla PER-1, bla OXA 23, bla OXA-24, bla OXA-51, bla OXA-58, and ISAba1 genes. All isolates were resistant to ceftazidime, ceftriaxone, and cefotaxime. All of the isolates revealed susceptibility to polymyxin B and colistin. Ninety-six percent of the isolates were extensive drug resistance (XDR), 5.6% extended spectrum beta lactamase (ESBL), and 54.8% metallo-beta-lactamase (MBL). All isolates were positive for bla OXA-51 and ISAba1. bla OXA-23, bla OXA-24, and bla OXA-58 were found in 79.8%, 25%, and 3.2%, respectively. The frequency rate of bla PER-1 gene was 52.4%. Multidrug resistant A. baumannii isolates are increasing in our setting and extensively limit therapeutic options. The high rate presence of class D carbapenemase-encoding genes, mainly bla OXA-23 carbapenemases, is worrying and alarming as an emerging threat in our hospital. PMID- 26881083 TI - Emergence of Tetracycline Resistant Vibrio cholerae O1 Biotype El Tor Serotype Ogawa with Classical ctxB Gene from a Cholera Outbreak in Odisha, Eastern India. AB - In September 2010, a cholera outbreak was reported from Odisha, Eastern India. V. cholerae isolated from the clinical samples were biochemically and serologically confirmed as serogroup O1, biotype El Tor, and serotype Ogawa. Multiplex PCR screening revealed the presence of various genes, namely, ompW, ctxB, zot, rfbO1, tcp, ace, hlyA, ompU, rtx, and toxR, in all of the isolates. The isolates were resistant to co-trimoxazole, nalidixic acid, polymyxin B, spectinomycin, streptomycin, sulfamethoxazole, tetracycline, trimethoprim, and vibriostatic agent 2,4-diamino-6,7-diisopropylpteridine (O/129). Minimum inhibitory concentration of tetracycline decreased in the presence of carbonyl cyanide m chlorophenylhydrazone (CCCP), suggesting the involvement of efflux pumps. PCR analysis confirmed the presence of class I integrons as well as SXT elements harbouring antibiotic resistance genes in all isolates. Sequencing revealed the presence of ctxB gene of classical biotype in all the isolates. The isolates harboured an RS1-CTX prophage array with El Tor type rstR and classical ctxB on the large chromosome. The study indicated that the V. cholerae El Tor variants are evolving in the area with better antibiotic resistance and virulence potential. PMID- 26881085 TI - Which Are the Most Relevant Questions in the Assessment of Outcome after Distal Radial Fractures? AB - A study was designed to determine which wrist scoring system best correlates with patient satisfaction and which individual variables predict a satisfactory outcome. We looked at forty-five females and 5 males with wrist fractures at 12 weeks after injury and compared their level of satisfaction with various respected outcome measures. The mean age was 66 years. Multivariate regression analysis was carried out using a statistical software package. Patient satisfaction correlated best with the MacDermid, Watts, and DASH scores. The variables in these scoring systems that predicted satisfaction were pain and ability to perform household chores or usual occupation, open packets, and cut meat. The four most important questions to ask in the clinic following wrist fractures are about severity of pain and ability to open packets, cut meat, and perform household chores or usual occupation. This may provide simple and more concise means of assessing outcome after distal radial fractures. Level of evidence is level 4. PMID- 26881084 TI - Role of Heat-Shock Proteins in Cellular Function and in the Biology of Fungi. AB - Stress (biotic or abiotic) is an unfavourable condition for an organism including fungus. To overcome stress, organism expresses heat-shock proteins (Hsps) or chaperons to perform biological function. Hsps are involved in various routine biological processes such as transcription, translation and posttranslational modifications, protein folding, and aggregation and disaggregation of proteins. Thus, it is important to understand holistic role of Hsps in response to stress and other biological conditions in fungi. Hsp104, Hsp70, and Hsp40 are found predominant in replication and Hsp90 is found in transcriptional and posttranscriptional process. Hsp90 and Hsp70 in combination or alone play a major role in morphogenesis and dimorphism. Heat stress in fungi expresses Hsp60, Hsp90, Hsp104, Hsp30, and Hsp10 proteins, whereas expression of Hsp12 protein was observed in response to cold stress. Hsp30, Hsp70, and Hsp90 proteins showed expression in response to pH stress. Osmotic stress is controlled by small heat shock proteins and Hsp60. Expression of Hsp104 is observed under high pressure conditions. Out of these heat-shock proteins, Hsp90 has been predicted as a potential antifungal target due to its role in morphogenesis. Thus, current review focuses on role of Hsps in fungi during morphogenesis and various stress conditions (temperature, pH, and osmotic pressure) and in antifungal drug tolerance. PMID- 26881086 TI - Computed Tomography Analysis of Postsurgery Femoral Component Rotation Based on a Force Sensing Device Method versus Hypothetical Rotational Alignment Based on Anatomical Landmark Methods: A Pilot Study. AB - Rotation of the femoral component is an important aspect of knee arthroplasty, due to its effects on postsurgery knee kinematics and associated functional outcomes. It is still debated which method for establishing rotational alignment is preferable in orthopedic surgery. We compared force sensing based femoral component rotation with traditional anatomic landmark methods to investigate which method is more accurate in terms of alignment to the true transepicondylar axis. Thirty-one patients underwent computer-navigated total knee arthroplasty for osteoarthritis with femoral rotation established via a force sensor. During surgery, three alternative hypothetical femoral rotational alignments were assessed, based on transepicondylar axis, anterior-posterior axis, or the utilization of a posterior condyles referencing jig. Postoperative computed tomography scans were obtained to investigate rotation characteristics. Significant differences in rotation characteristics were found between rotation according to DKB and other methods (P < 0.05). Soft tissue balancing resulted in smaller deviation from anatomical epicondylar axis than any other method. 77% of operated knees were within a range of +/-3 degrees of rotation. Only between 48% and 52% of knees would have been rotated appropriately using the other methods. The current results indicate that force sensors may be valuable for establishing correct femoral rotation. PMID- 26881087 TI - Three-Dimensional Analysis of the Contact Pattern between the Cortical Bone and Femoral Prosthesis after Cementless Total Hip Arthroplasty. AB - The cementless stem Excia (B. Braun, Melsungen, Germany) implant has a rectangular cross-sectional shape with back-and-forth flanges and a plasma sprayed, dicalcium phosphate dihydrate coating from the middle to proximal portion to increase initial fixation and early bone formation. Here, the conformity of the Excia stem to the femoral canal morphology was three dimensionally assessed using computed tomography. Forty-three patients (45 hips) were examined after primary total hip arthroplasty with a mean follow-up of 27 +/ 3 months (range: 24-36 months). Spot welds occurred at zone 2 in 16 hips and at zone 6 in 24 hips, with 83% (20/24 hips) of those occurring within 3 months after surgery. First- (n = 12 hips), second- (n = 32), and third- (n = 1) degree stress shielding were observed. The stem was typically in contact with the cortical bone in the anterolateral mid-portion (100%) and posteromedial distal portions (85%). Stress shielding did not progress, even in cases where the stems were in contact with the distal portions. The anterior flange was in contact with the bone in all cases. The stability of the mid-lateral portion with the dicalcium phosphate dihydrate coating and the anterior flange may have inhibited the progression of stress shielding beyond the second degree. PMID- 26881088 TI - Five-Minute Awake Snoring Test for Determining CPAP Pressures (Five-Minute CPAP Test): A Pilot Study. AB - Objective. To develop a quick, simple, bedside test for determining continuous positive airway pressures (CPAP) for obstructive sleep apnea (OSA) patients. Study Design. Prospective case series at a tertiary medical center. Methods. The Five-Minute Awake Snoring Test for Determining CPAP (Five-Minute CPAP Test) was developed and tested. Patients wear a soft-gel nasal triangle mask while holding a tongue depressor with the wide section (1.75 cm) between the teeth. Fixed pressure nasal CPAP is applied while the patient simulates snoring at 4 centimeters of water pressure. The pressure is incrementally titrated up and then down to determine the lowest pressure at which the patient cannot snore (Quiet Pressure). Results. Overall, thirty-eight patients participated. All could simulate snoring. Correlation coefficients were statistically significant between Quiet Pressures and body mass index (r s = 0.60 [strong positive relationship], p = 0.0088), apnea-hypopnea index (r s = 0.49 [moderate positive relationship], p = 0.039), lowest oxygen saturation (r s = -0.47 [moderate negative relationship], p = 0.048), and oxygen desaturation index (r s = 0.62 [strong positive relationship], p = 0.0057). Conclusion. This pilot study introduces a new concept, which is the final product of over one year of exploration, development, and testing. Five-Minute CPAP Test is a quick, inexpensive, and safe bedside test based on supine awake simulated snoring with nasal CPAP. PMID- 26881089 TI - Neural Plasticity following Abacus Training in Humans: A Review and Future Directions. AB - The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact. PMID- 26881092 TI - CNS Plasticity in Injury and Disease. PMID- 26881090 TI - Perspectives of TRPV1 Function on the Neurogenesis and Neural Plasticity. AB - The development of new strategies to renew and repair neuronal networks using neural plasticity induced by stem cell graft could enable new therapies to cure diseases that were considered lethal until now. In adequate microenvironment a neuronal progenitor must receive molecular signal of a specific cellular context to determine fate, differentiation, and location. TRPV1, a nonselective calcium channel, is expressed in neurogenic regions of the brain like the subgranular zone of the hippocampal dentate gyrus and the telencephalic subventricular zone, being valuable for neural differentiation and neural plasticity. Current data show that TRPV1 is involved in several neuronal functions as cytoskeleton dynamics, cell migration, survival, and regeneration of injured neurons, incorporating several stimuli in neurogenesis and network integration. The function of TRPV1 in the brain is under intensive investigation, due to multiple places where it has been detected and its sensitivity for different chemical and physical agonists, and a new role of TRPV1 in brain function is now emerging as a molecular tool for survival and control of neural stem cells. PMID- 26881091 TI - Abnormal Pressure Pain, Touch Sensitivity, Proprioception, and Manual Dexterity in Children with Autism Spectrum Disorders. AB - Children with autism spectrum disorders (ASD) often display an abnormal reactivity to tactile stimuli, altered pain perception, and lower motor skills than healthy children. Nevertheless, these motor and sensory deficits have been mostly assessed by using clinical observation and self-report questionnaires. The present study aims to explore somatosensory and motor function in children with ASD by using standardized and objective testing procedures. METHODS: Tactile and pressure pain thresholds in hands and lips, stereognosis, proprioception, and fine motor performance of the upper limbs were assessed in high-functioning children with ASD (n = 27) and compared with typically developing peers (n = 30). RESULTS: Children with ASD showed increased pain sensitivity, increased touch sensitivity in C-tactile afferents innervated areas, and diminished fine motor performance and proprioception compared to healthy children. No group differences were observed for stereognosis. CONCLUSION: Increased pain sensitivity and increased touch sensitivity in areas classically related to affective touch (C tactile afferents innervated areas) may explain typical avoiding behaviors associated with hypersensitivity. Both sensory and motor impairments should be assessed and treated in children with ASD. PMID- 26881093 TI - Node Detection Using High-Dimensional Fuzzy Parcellation Applied to the Insular Cortex. AB - Several functional connectivity approaches require the definition of a set of regions of interest (ROIs) that act as network nodes. Different methods have been developed to define these nodes and to derive their functional and effective connections, most of which are rather complex. Here we aim to propose a relatively simple "one-step" border detection and ROI estimation procedure employing the fuzzy c-mean clustering algorithm. To test this procedure and to explore insular connectivity beyond the two/three-region model currently proposed in the literature, we parcellated the insular cortex of 20 healthy right-handed volunteers scanned in a resting state. By employing a high-dimensional functional connectivity-based clustering process, we confirmed the two patterns of connectivity previously described. This method revealed a complex pattern of functional connectivity where the two previously detected insular clusters are subdivided into several other networks, some of which are not commonly associated with the insular cortex, such as the default mode network and parts of the dorsal attentional network. Furthermore, the detection of nodes was reliable, as demonstrated by the confirmative analysis performed on a replication group of subjects. PMID- 26881094 TI - Neural Hyperactivity of the Central Auditory System in Response to Peripheral Damage. AB - It is increasingly appreciated that cochlear pathology is accompanied by adaptive responses in the central auditory system. The cause of cochlear pathology varies widely, and it seems that few commonalities can be drawn. In fact, despite intricate internal neuroplasticity and diverse external symptoms, several classical injury models provide a feasible path to locate responses to different peripheral cochlear lesions. In these cases, hair cell damage may lead to considerable hyperactivity in the central auditory pathways, mediated by a reduction in inhibition, which may underlie some clinical symptoms associated with hearing loss, such as tinnitus. Homeostatic plasticity, the most discussed and acknowledged mechanism in recent years, is most likely responsible for excited central activity following cochlear damage. PMID- 26881097 TI - Chronic Mild Stress Modulates Activity-Dependent Transcription of BDNF in Rat Hippocampal Slices. AB - Although activity-dependent transcription represents a crucial mechanism for long lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). The ex vivo methodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress related diseases. PMID- 26881096 TI - Lasting Differential Effects on Plasticity Induced by Prenatal Stress in Dorsal and Ventral Hippocampus. AB - Early life adversaries have a profound impact on the developing brain structure and functions that persist long after the original traumatic experience has vanished. One of the extensively studied brain structures in relation to early life stress has been the hippocampus because of its unique association with cognitive processes of the brain. While the entire hippocampus shares the same intrinsic organization, it assumes different functions in its dorsal and ventral sectors (DH and VH, resp.), based on different connectivity with other brain structures. In the present review, we summarize the differences between DH and VH and discuss functional and structural effects of prenatal stress in the two sectors, with the realization that much is yet to be explored in understanding the opposite reactivity of the DH and VH to stressful stimulation. PMID- 26881095 TI - Obesity Reduces Cognitive and Motor Functions across the Lifespan. AB - Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID- 26881098 TI - Hippocampal Dendritic Spines Are Segregated Depending on Their Actin Polymerization. AB - Dendritic spines are mushroom-shaped protrusions of the postsynaptic membrane. Spines receive the majority of glutamatergic synaptic inputs. Their morphology, dynamics, and density have been related to synaptic plasticity and learning. The main determinant of spine shape is filamentous actin. Using FRAP, we have reexamined the actin dynamics of individual spines from pyramidal hippocampal neurons, both in cultures and in hippocampal organotypic slices. Our results indicate that, in cultures, the actin mobile fraction is independently regulated at the individual spine level, and mobile fraction values do not correlate with either age or distance from the soma. The most significant factor regulating actin mobile fraction was the presence of astrocytes in the culture substrate. Spines from neurons growing in the virtual absence of astrocytes have a more stable actin cytoskeleton, while spines from neurons growing in close contact with astrocytes show a more dynamic cytoskeleton. According to their recovery time, spines were distributed into two populations with slower and faster recovery times, while spines from slice cultures were grouped into one population. Finally, employing fast lineal acquisition protocols, we confirmed the existence of loci with high polymerization rates within the spine. PMID- 26881099 TI - The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications. AB - Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ?9 tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing. PMID- 26881100 TI - Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer's Disease: A Diffusion MRI Study with DTI and HARDI Models. AB - Alzheimer's disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels. PMID- 26881101 TI - Defining Optimal Aerobic Exercise Parameters to Affect Complex Motor and Cognitive Outcomes after Stroke: A Systematic Review and Synthesis. AB - Although poststroke aerobic exercise (AE) increases markers of neuroplasticity and protects perilesional tissue, the degree to which it enhances complex motor or cognitive outcomes is unknown. Previous research suggests that timing and dosage of exercise may be important. We synthesized data from clinical and animal studies in order to determine optimal AE training parameters and recovery outcomes for future research. Using predefined criteria, we included clinical trials of stroke of any type or duration and animal studies employing any established models of stroke. Of the 5,259 titles returned, 52 articles met our criteria, measuring the effects of AE on balance, lower extremity coordination, upper limb motor skills, learning, processing speed, memory, and executive function. We found that early-initiated low-to-moderate intensity AE improved locomotor coordination in rodents. In clinical trials, AE improved balance and lower limb coordination irrespective of intervention modality or parameter. In contrast, fine upper limb recovery was relatively resistant to AE. In terms of cognitive outcomes, poststroke AE in animals improved memory and learning, except when training was too intense. However, in clinical trials, combined training protocols more consistently improved cognition. We noted a paucity of studies examining the benefits of AE on recovery beyond cessation of the intervention. PMID- 26881103 TI - The Role of Perspective in Mental Time Travel. AB - Recent years have seen accumulating evidence for the proposition that people process time by mapping it onto a linear spatial representation and automatically "project" themselves on an imagined mental time line. Here, we ask whether people can adopt the temporal perspective of another person when travelling through time. To elucidate similarities and differences between time travelling from one's own perspective or from the perspective of another person, we asked participants to mentally project themselves or someone else (i.e., a coexperimenter) to different time points. Three basic properties of mental time travel were manipulated: temporal location (i.e., where in time the travel originates: past, present, and future), motion direction (either backwards or forwards), and temporal duration (i.e., the distance to travel: one, three, or five years). We found that time travels originating in the present lasted longer in the self- than in the other-perspective. Moreover, for self-perspective, but not for other-perspective, time was differently scaled depending on where in time the travel originated. In contrast, when considering the direction and the duration of time travelling, no dissimilarities between the self- and the other perspective emerged. These results suggest that self- and other-projection, despite some differences, share important similarities in structure. PMID- 26881102 TI - Is the Frequency in Somatosensory Electrical Stimulation the Key Parameter in Modulating the Corticospinal Excitability of Healthy Volunteers and Stroke Patients with Spasticity? AB - Somatosensory electrical stimulation (SES) has been proposed as an approach to treat patients with sensory-motor impairment such as spasticity. However, there is still no consensus regarding which would be the adequate SES parameters to treat those deficits. Therefore, the aim of this study was to evaluate the effects of applying SES over the forearm muscles at four different frequencies of stimulation (3, 30, 150, and 300 Hz) and in two intervals of time (5' and 30') by means of transcranial magnetic stimulation and Hoffmann's reflex (H-reflex) in healthy volunteers (Experiments I and II). A group of stroke patients (Experiment III) was also preliminary evaluated to ascertain SES effects at a low frequency (3 Hz) applied for 30' over the forearm spastic flexors muscles by measuring the wrist joint passive torque. Motor evoked potentials and the H reflex were collected from different forearm and hand muscles immediately before and after SES and up to 5' (Experiment I) and 10' (Experiments I and II) later. None of the investigated frequencies of SES was able to operate as a key in switching modulatory effects in the central nervous system of healthy volunteers and stroke patients with spasticity. PMID- 26881104 TI - Transplantation of Neural Stem Cells Cotreated with Thyroid Hormone and GDNF Gene Induces Neuroprotection in Rats of Chronic Experimental Allergic Encephalomyelitis. AB - The present study investigates whether transplantation of NSCs treated with T3 alone (T3/NSCs), or in conjunction with GDNF gene (GDNF-T3/NSCs), provides a better therapeutic effect than NSCs for chronic EAE. EAE rats were, respectively, injected with NSCs, T3/NSCs, GDNF-T3/NSCs, and saline at 10 days and sacrificed at 60 days after EAE immunization. The three cell grafted groups showed a significant reduction in clinical scores, inflammatory infiltration, and demyelination compared with the saline-injected group, and among the cell grafted groups, the reduction in GDNF-T3/NSCs group was the most notable, followed by T3/NSCs group. Grafted T3/NSCs and GDNF-T3/NSCs acquired more MAP2, GalC, and less GFAP in brain compared with grafted NSCs, and grafted GDNF-T3/NSCs acquired most MAP2 and least GalC among the cell grafted groups. Furthermore, T3/NSCs and GDNF-T3/NSCs grafting increased the expression of mRNA for PDGFalphaR, GalC, and MBP in lesion areas of brain compared with NSCs grafting, and the expression of mRNA for GalC and MBP in GDNF-T3/NSCs group was higher than that in T3/NSCs group. In conclusion, T3/NSCs grafting, especially GDNF-T3/NSCs grafting, provides a better neuroprotective effect for EAE than NSCs transplantation. PMID- 26881105 TI - The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis. AB - The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development. They represent important factors in neurite growth and formation of neural circuits. There is evidence suggesting that the newly generated hypothalamic neurons may be involved in regulation of metabolism, energy balance, body weight, and social behavior as well. Here we review recent data on the role of hypothalamic neuropeptides in adult neurogenesis and neuritogenesis with special emphasis on the development of food intake and social behavior related brain circuits. PMID- 26881106 TI - Effects of Patterned Sound Deprivation on Short- and Long-Term Plasticity in the Rat Thalamocortical Auditory System In Vivo. AB - Postnatal sensory experience plays a significant role in the maturation and synaptic stabilization of sensory cortices, such as the primary auditory cortex (A1). Here, we examined the effects of patterned sound deprivation (by rearing in continuous white noise, WN) during early postnatal life on short- and long-term plasticity of adult male rats using an in vivo preparation (urethane anesthesia). Relative to age-matched control animals reared under unaltered sound conditions, rats raised in WN (from postnatal day 5 to 50-60) showed greater levels of long term potentiation (LTP) of field potentials in A1 induced by theta-burst stimulation (TBS) of the medial geniculate nucleus (MGN). In contrast, analyses of short-term plasticity using paired-pulse stimulation (interstimulus intervals of 25-1000 ms) did not reveal any significant effects of WN rearing. However, LTP induction resulted in a significant enhancement of paired-pulse depression (PPD) for both rearing conditions. We conclude that patterned sound deprivation during early postnatal life results in the maintenance of heightened, juvenile-like long term plasticity (LTP) into adulthood. Further, the enhanced PPD following LTP induction provides novel evidence that presynaptic mechanisms contribute to thalamocortical LTP in A1 under in vivo conditions. PMID- 26881107 TI - The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-beta-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex. AB - The amyloid-beta peptide or Abeta is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Abeta appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Abeta peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Abeta induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Abeta-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Abeta increase and RA decrease probably lead to a pathological state. PMID- 26881108 TI - Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons. AB - The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer's disease (AD). To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42) treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain. PMID- 26881109 TI - N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth. AB - Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life. PMID- 26881110 TI - The Galphao Activator Mastoparan-7 Promotes Dendritic Spine Formation in Hippocampal Neurons. AB - Mastoparan-7 (Mas-7), an analogue of the peptide mastoparan, which is derived from wasp venom, is a direct activator of Pertussis toxin- (PTX-) sensitive G proteins. Mas-7 produces several biological effects in different cell types; however, little is known about how Mas-7 influences mature hippocampal neurons. We examined the specific role of Mas-7 in the development of dendritic spines, the sites of excitatory synaptic contact that are crucial for synaptic plasticity. We report here that exposure of hippocampal neurons to a low dose of Mas-7 increases dendritic spine density and spine head width in a time-dependent manner. Additionally, Mas-7 enhances postsynaptic density protein-95 (PSD-95) clustering in neurites and activates Galpha(o) signaling, increasing the intracellular Ca(2+) concentration. To define the role of signaling intermediates, we measured the levels of phosphorylated protein kinase C (PKC), c Jun N-terminal kinase (JNK), and calcium-calmodulin dependent protein kinase IIalpha (CaMKIIalpha) after Mas-7 treatment and determined that CaMKII activation is necessary for the Mas-7-dependent increase in dendritic spine density. Our results demonstrate a critical role for Galpha(o) subunit signaling in the regulation of synapse formation. PMID- 26881111 TI - Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia. AB - The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke. PMID- 26881112 TI - Seeding Stress Resilience through Inoculation. AB - Stress is a generalized set of physiological and psychological responses observed when an organism is placed under challenging circumstances. The stress response allows organisms to reattain the equilibrium in face of perturbations. Unfortunately, chronic and/or traumatic exposure to stress frequently overwhelms coping ability of an individual. This is manifested as symptoms affecting emotions and cognition in stress-related mental disorders. Thus environmental interventions that promote resilience in face of stress have much clinical relevance. Focus of the bulk of relevant neurobiological research at present remains on negative aspects of health and psychological outcomes of stress exposure. Yet exposure to the stress itself can promote resilience to subsequent stressful episodes later in the life. This is especially true if the prior stress occurs early in life, is mild in its magnitude, and is controllable by the individual. This articulation has been referred to as "stress inoculation," reminiscent of resilience to the pathology generated through vaccination by attenuated pathogen itself. Using experimental evidence from animal models, this review explores relationship between nature of the "inoculum" stress and subsequent psychological resilience. PMID- 26881113 TI - TLR4 Signaling in MPP+-Induced Activation of BV-2 Cells. AB - AIMS: This work was conducted to establish an in vitro Parkinson's disease (PD) model by exposing BV-2 cells to 1-methyl-4-phenylpyridinium (MPP(+)) and exploring the roles of TLR2/TLR4/TLR9 in inflammatory responses to MPP(+). METHODS/RESULTS: MTT assay showed that cell viability of BV-2 cells was 84.78 +/- 0.86% and 81.18 +/- 0.99% of the control after incubation with 0.1 mM MPP(+) for 12 hours and 24 hours, respectively. Viability was not significantly different from the control group. With immunofluorescence technique, we found that MPP(+) incubation at 0.1 mM for 12 hours was the best condition to activate BV-2 cells. In this condition, the levels of TNF-alpha, IL-1beta, and iNOS protein were statistically increased compared to the control according to ELISA tests. Real time RT-PCR and western blot measurements showed that TLR4 was statistically increased after 0.1 mM MPP(+) incubation for 12 hours. Furthermore, after siRNA interference of TLR4 mRNA, NF-kappaB activation and the levels of TNF-alpha, IL 1beta, and iNOS were all statistically decreased in this cell model. CONCLUSION: MPP(+) incubation at the concentration of 0.1 mM for 12 hours is the best condition to activate BV-2 cells for mimicking PD inflammation in BV-2 cells. TLR4 signalling plays a critical role in the activation of BV-2 cells and the induction of inflammation in this cell model. PMID- 26881115 TI - Body Perception and Action Following Deafness. AB - The effect of deafness on sensory abilities has been the topic of extensive investigation over the past decades. These investigations have mostly focused on visual capacities. We are only now starting to investigate how the deaf experience their own bodies and body-related abilities. Indeed, a growing corpus of research suggests that auditory input could play an important role in body related processing. Deafness could therefore disturb such processes. It has also been suggested that many unexplained daily difficulties experienced by the deaf could be related to deficits in this underexplored field. In the present review, we propose an overview of the current state of knowledge on the effects of deafness on body-related processing. PMID- 26881116 TI - Self-Rated Attentiveness Interacts with Transcranial Direct Current Stimulation and Noise Stimulation in Reaction Time in a Go/No-Go Task. AB - Previous research has found that stimulating inattentive people with auditory white noise induces enhancement in cognitive performance. This enhancement is believed to occur due to a statistical phenomenon called stochastic resonance, where noise increases the probability of a signal passing the firing threshold in the neural cells. Here we investigate whether people with low attentiveness benefit to a larger extent than attentive people from stimulation by auditory white noise and transcranial direct current stimulation (tDCS). The results show, for both auditory noise and tDCS stimulation, that the changes in performance relative to nonstimulation correlate with the degree of attentiveness in a Go/No Go task, but not in a N-back task. These results suggest that the benefit of tDCS may interact with inattentiveness. PMID- 26881118 TI - Multisession Anodal tDCS Protocol Improves Motor System Function in an Aging Population. AB - OBJECTIVES: The primary objective of this study was to investigate the effects of five consecutive, daily 20-minute sessions of M1 a-tDCS on motor learning in healthy, cognitively intact, aging adults. DESIGN: A total of 23 participants (51 to 69 years old) performed five consecutive, daily 20-minute sessions of a serial reaction time task (SRT task) concomitant with either anodal (n = 12) or sham (n = 11) M1 a-tDCS. RESULTS: We found a significant group * training sessions interaction, indicating that whereas aging adults in the sham group exhibited little-to-no sequence-specific learning improvements beyond the first day of training, reproducible improvements in the ability to learn new motor sequences over 5 consecutive sessions were the net result in age-equivalent participants from the M1 a-tDCS group. A significant main effect of group on sequence-specific learning revealed greater motor learning for the M1 a-tDCS group when the five learning sessions were averaged. CONCLUSION: These findings raise into prominence the utility of multisession anodal TDCS protocols in combination with motor training to help prevent/alleviate age-associated motor function decline. PMID- 26881114 TI - Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets. AB - Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe an in vitro approach that allows for the investigation of ECM functions for synaptogenesis. PMID- 26881117 TI - Effects of Fast Simple Numerical Calculation Training on Neural Systems. AB - Cognitive training, including fast simple numerical calculation (FSNC), has been shown to improve performance on untrained processing speed and executive function tasks in the elderly. However, the effects of FSNC training on cognitive functions in the young and on neural mechanisms remain unknown. We investigated the effects of 1-week intensive FSNC training on cognitive function, regional gray matter volume (rGMV), and regional cerebral blood flow at rest (resting rCBF) in healthy young adults. FSNC training was associated with improvements in performance on simple processing speed, speeded executive functioning, and simple and complex arithmetic tasks. FSNC training was associated with a reduction in rGMV and an increase in resting rCBF in the frontopolar areas and a weak but widespread increase in resting rCBF in an anatomical cluster in the posterior region. These results provide direct evidence that FSNC training alone can improve performance on processing speed and executive function tasks as well as plasticity of brain structures and perfusion. Our results also indicate that changes in neural systems in the frontopolar areas may underlie these cognitive improvements. PMID- 26881119 TI - Distribution of N-Acetylgalactosamine-Positive Perineuronal Nets in the Macaque Brain: Anatomy and Implications. AB - Perineuronal nets (PNNs) are extracellular molecules that form around neurons near the end of critical periods during development. They surround neuronal cell bodies and proximal dendrites. PNNs inhibit the formation of new connections and may concentrate around rapidly firing inhibitory interneurons. Previous work characterized the important role of perineuronal nets in plasticity in the visual system, amygdala, and spinal cord of rats. In this study, we use immunohistochemistry to survey the distribution of perineuronal nets in representative areas of the primate brain. We also document changes in PNN prevalence in these areas in animals of different ages. We found that PNNs are most prevalent in the cerebellar nuclei, surrounding >90% of the neurons there. They are much less prevalent in cerebral cortex, surrounding less than 10% of neurons in every area that we examined. The incidence of perineuronal nets around parvalbumin-positive neurons (putative fast-spiking interneurons) varies considerably between different areas in the brain. Our survey indicates that the presence of PNNs may not have a simple relationship with neural plasticity and may serve multiple functions in the central nervous system. PMID- 26881121 TI - Motor Cortex Plasticity during Unilateral Finger Movement with Mirror Visual Feedback. AB - Plasticity is one of the most important physiological mechanisms underlying motor recovery from brain lesions. Rehabilitation methods, such as mirror visual feedback therapy, which are based on multisensory integration of motor, cognitive, and perceptual processes, are considered effective methods to induce cortical reorganization. The present study investigated 3 different types of visual feedback (direct, mirrored, and blocked visual feedback: DVF, MVF, and BVF, resp.) on M1 cortex excitability and intracortical inhibition/facilitation at rest and during phasic unimanual motor task in 11 healthy individuals. The excitability of the ipsilateral M1 cortex and the intracortical facilitation increased during motor task performance in the DVF and MVF but not in the BVF condition. In addition, MVF induced cortical disinhibition of the ipsilateral hemisphere to the index finger performing the motor task, which was greater when compared to the BVF and restricted to the homologue first dorsal interosseous muscle. The visual feedback is relevant to M1 cortex excitability modulation but the MVF plays a crucial role in promoting changes in intracortical inhibition in comparison to BVF. Altogether, it can be concluded that a combination of motor training with MVF therapy may induce more robust neuroplastic changes through multisensory integration that is relevant to motor rehabilitation. PMID- 26881120 TI - Simultaneous Assessment of White Matter Changes in Microstructure and Connectedness in the Blind Brain. AB - Magnetic resonance imaging (MRI) of the human brain has provided converging evidence that visual deprivation induces regional changes in white matter (WM) microstructure. It remains unclear how these changes modify network connections between brain regions. Here we used diffusion-weighted MRI to relate differences in microstructure and structural connectedness of WM in individuals with congenital or late-onset blindness relative to normally sighted controls. Diffusion tensor imaging (DTI) provided voxel-specific microstructural features of the tissue, while anatomical connectivity mapping (ACM) assessed the connectedness of each voxel with the rest of the brain. ACM yielded reduced anatomical connectivity in the corpus callosum in individuals with congenital but not late-onset blindness. ACM did not identify any brain region where blindness resulted in increased anatomical connectivity. DTI revealed widespread microstructural differences as indexed by a reduced regional fractional anisotropy (FA). Blind individuals showed lower FA in the primary visual and the ventral visual processing stream relative to sighted controls regardless of the blindness onset. The results show that visual deprivation shapes WM microstructure and anatomical connectivity, but these changes appear to be spatially dissociated as changes emerge in different WM tracts. They also indicate that regional differences in anatomical connectivity depend on the onset of blindness. PMID- 26881123 TI - Large and Small Dendritic Spines Serve Different Interacting Functions in Hippocampal Synaptic Plasticity and Homeostasis. AB - The laying down of memory requires strong stimulation resulting in specific changes in synaptic strength and corresponding changes in size of dendritic spines. Strong stimuli can also be pathological, causing a homeostatic response, depressing and shrinking the synapse to prevent damage from too much Ca(2+) influx. But do all types of dendritic spines serve both of these apparently opposite functions? Using confocal microscopy in organotypic slices from mice expressing green fluorescent protein in hippocampal neurones, the size of individual spines along sections of dendrite has been tracked in response to application of tetraethylammonium. This strong stimulus would be expected to cause both a protective homeostatic response and long-term potentiation. We report separation of these functions, with spines of different sizes reacting differently to the same strong stimulus. The immediate shrinkage of large spines suggests a homeostatic protective response during the period of potential danger. In CA1, long-lasting growth of small spines subsequently occurs consolidating long-term potentiation but only after the large spines return to their original size. In contrast, small spines do not change in dentate gyrus where potentiation does not occur. The separation in time of these changes allows clear functional differentiation of spines of different sizes. PMID- 26881122 TI - Neuroprotective Transcription Factors in Animal Models of Parkinson Disease. AB - A number of transcription factors, including En1/2, Foxa1/2, Lmx1a/b, Nurr1, Otx2, and Pitx3, with key roles in midbrain dopaminergic (mDA) neuron development, also regulate adult mDA neuron survival and physiology. Mouse models with targeted disruption of some of these genes display several features reminiscent of Parkinson disease (PD), in particular the selective and progressive loss of mDA neurons in the substantia nigra pars compacta (SNpc). The characterization of these animal models has provided valuable insights into various mechanisms of PD pathogenesis. Therefore, the dissection of the mechanisms and survival signalling pathways engaged by these transcription factors to protect mDA neuron from degeneration can suggest novel therapeutic strategies. The work on En1/2-mediated neuroprotection also highlights the potential of protein transduction technology for neuroprotective approaches in PD. PMID- 26881124 TI - Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice. AB - Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice. PMID- 26881125 TI - Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait. AB - Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction. PMID- 26881126 TI - Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner. AB - N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here, we tested whether LFS-induced DP is also altered in pathological GluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit specific blocker Ro 25-6981 (1 MUM) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor dependence, we applied the NMDA receptor antagonist D-AP5 (50 MUM) prior to LFS and observed that DP was abolished in both control and post-SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS DP clearly required NMDA receptor activation, GluN2B-containing NMDA receptors were not involved in this form of depotentiation. PMID- 26881127 TI - Systematic Underreproduction of Time Is Independent of Judgment Certainty. AB - We recently proposed that systematic underreproduction of time is caused by a general judgment bias towards earlier responses, instead of reflecting a genuine misperception of temporal intervals. Here we tested whether this bias can be explained by the uncertainty associated with temporal judgments. We applied transcranial magnetic stimulation (TMS) to inhibit neuronal processes in the right posterior parietal cortex (PPC) and tested its effects on time discrimination and reproduction tasks. The results show increased certainty for discriminative time judgments after PPC inhibition. They suggest that the right PPC plays an inhibitory role for time perception, possibly by mediating the multisensory integration between temporal stimuli and other quantities. Importantly, this increased judgment certainty had no influence on the degree of temporal underreproduction. We conclude that the systematic underreproduction of time is not caused by uncertainty for temporal judgments. PMID- 26881128 TI - Transcriptional Control of Synaptic Plasticity by Transcription Factor NF-kappaB. AB - Activation of nuclear factor kappa B (NF-kappaB) transcription factors is required for the induction of synaptic plasticity and memory formation. All components of this signaling pathway are localized at synapses, and transcriptionally active NF-kappaB dimers move to the nucleus to translate synaptic signals into altered gene expression. Neuron-specific inhibition results in altered connectivity of excitatory and inhibitory synapses and functionally in selective learning deficits. Recent research on transgenic mice with impaired or hyperactivated NF-kappaB gave important insights into plasticity-related target gene expression that is regulated by NF-kappaB. In this minireview, we update the available data on the role of this transcription factor for learning and memory formation and comment on cross-sectional activation of NF-kappaB in the aged and diseased brain that may directly or indirectly affect kappaB-dependent transcription of synaptic genes. PMID- 26881129 TI - Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation. AB - Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID- 26881130 TI - Compensation of Vestibular Function and Plasticity of Vestibular Nucleus after Unilateral Cochleostomy. AB - Dizziness and vertigo frequently occur after cochlear implantation (CI) surgery, particularly during the early stages. It could recover over time but some of the patients suffered from delayed or sustained vestibular symptoms after CI. This study used rat animal models to investigate the effect of unilateral cochleostomy on the vestibular organs over time. Twenty-seven Sprague Dawley rats underwent cochleostomy to evaluate the postoperative changes in hearing threshold, gain and symmetry of the vestibular ocular response, overall balance function, number of hair cells in the crista, and the c-Fos activity in the brainstem vestibular nucleus. Loss of vestibular function was observed during the early stages, but function recovered partially over time. Histopathological findings demonstrated a mild decrease in vestibular hair cells numbers. Increased c-Fos immunoreactivity in the vestibular nucleus, observed in the early stages after cochleostomy, decreased over time. Cochleostomy is a risk factor for peripheral vestibular organ damage that can cause functional impairment in the peripheral vestibular organs. Altered vestibular nucleus activity may be associated with vestibular compensation and plasticity after unilateral cochleostomy. PMID- 26881131 TI - Potential Role of JAK-STAT Signaling Pathway in the Neurogenic-to-Gliogenic Shift in Down Syndrome Brain. AB - Trisomy of human chromosome 21 in Down syndrome (DS) leads to several phenotypes, such as mild-to-severe intellectual disability, hypotonia, and craniofacial dysmorphisms. These are fundamental hallmarks of the disorder that affect the quality of life of most individuals with DS. Proper brain development involves meticulous regulation of various signaling pathways, and dysregulation may result in abnormal neurodevelopment. DS brain is characterized by an increased number of astrocytes with reduced number of neurons. In mouse models for DS, the pool of neural progenitor cells commits to glia rather than neuronal cell fate in the DS brain. However, the mechanism(s) and consequences of this slight neurogenic-to gliogenic shift in DS brain are still poorly understood. To date, Janus kinase signal transducer and activator of transcription (JAK-STAT) signaling has been proposed to be crucial in various developmental pathways, especially in promoting astrogliogenesis. Since both human and mouse models of DS brain exhibit less neurons and a higher percentage of cells with astrocytic phenotypes, understanding the role of JAK-STAT signaling in DS brain development will provide novel insight into its role in the pathogenesis of DS brain and may serve as a potential target for the development of effective therapy to improve DS cognition. PMID- 26881132 TI - Otx2-PNN Interaction to Regulate Cortical Plasticity. AB - The ability of the environment to shape cortical function is at its highest during critical periods of postnatal development. In the visual cortex, critical period onset is triggered by the maturation of parvalbumin inhibitory interneurons, which gradually become surrounded by a specialized glycosaminoglycan-rich extracellular matrix: the perineuronal nets. Among the identified factors regulating cortical plasticity in the visual cortex, extracortical homeoprotein Otx2 is transferred specifically into parvalbumin interneurons and this transfer regulates both the onset and the closure of the critical period of plasticity for binocular vision. Here, we review the interaction between the complex sugars of the perineuronal nets and homeoprotein Otx2 and how this interaction regulates cortical plasticity during critical period and in adulthood. PMID- 26881134 TI - Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity. AB - Synapses mediate communication between neurons and enable the brain to change in response to experience, which is essential for learning and memory. The sites of most excitatory synapses in the brain, dendritic spines, undergo rapid remodeling that is important for neural circuit formation and synaptic plasticity. Abnormalities in synapse and spine formation and plasticity are associated with a broad range of brain disorders, including intellectual disabilities, autism spectrum disorders (ASD), and schizophrenia. Thus, elucidating the mechanisms that regulate these neuronal processes is critical for understanding brain function and disease. The brain-specific angiogenesis inhibitor (BAI) subfamily of adhesion G-protein-coupled receptors (adhesion-GPCRs) has recently emerged as central regulators of synapse development and plasticity. In this review, we will summarize the current knowledge regarding the roles of BAIs at synapses, highlighting their regulation, downstream signaling, and physiological functions, while noting the roles of other adhesion-GPCRs at synapses. We will also discuss the relevance of BAIs in various neurological and psychiatric disorders and consider their potential importance as pharmacological targets in the treatment of these diseases. PMID- 26881135 TI - Endogenous and Synthetic Cannabinoids as Therapeutics in Retinal Disease. AB - The functional significance of cannabinoids in ocular physiology and disease has been reported some decades ago. In the early 1970s, subjects who smoked Cannabis sativa developed lower intraocular pressure (IOP). This led to the isolation of phytocannabinoids from this plant and the study of their therapeutic effects in glaucoma. The main treatment of this disease to date involves the administration of drugs mediating either the decrease of aqueous humour synthesis or the increase of its outflow and thus reduces IOP. However, the reduction of IOP is not sufficient to prevent visual field loss. Retinal diseases, such as glaucoma and diabetic retinopathy, have been defined as neurodegenerative diseases and characterized by ischemia-induced excitotoxicity and loss of retinal neurons. Therefore, new therapeutic strategies must be applied in order to target retinal cell death, reduction of visual acuity, and blindness. The aim of the present review is to address the neuroprotective and therapeutic potential of cannabinoids in retinal disease. PMID- 26881133 TI - Dendritic Spines in Depression: What We Learned from Animal Models. AB - Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and spine density. Therefore, understanding dendritic spines is vital for uncovering the mechanisms underlying depression. Several chronic stress models, including chronic restraint stress (CRS), chronic unpredictable mild stress (CUMS), and chronic social defeat stress (CSDS), have been used to recapitulate depression-like behaviors in rodents and study the underlying mechanisms. In comparison with CRS, CUMS overcomes the stress habituation and has been widely used to model depression like behaviors. CSDS is one of the most frequently used models for depression, but it is limited to the study of male mice. Generally, chronic stress causes dendritic atrophy and spine loss in the neurons of the hippocampus and prefrontal cortex. Meanwhile, neurons of the amygdala and nucleus accumbens exhibit an increase in spine density. These alterations induced by chronic stress are often accompanied by depression-like behaviors. However, the underlying mechanisms are poorly understood. This review summarizes our current understanding of the chronic stress-induced remodeling of dendritic spines in the hippocampus, prefrontal cortex, orbitofrontal cortex, amygdala, and nucleus accumbens and also discusses the putative underlying mechanisms. PMID- 26881138 TI - The Effects of Leptin Replacement on Neural Plasticity. AB - Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID- 26881137 TI - Current Research Therapeutic Strategies for Alzheimer's Disease Treatment. AB - Alzheimer's disease (AD) currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Abeta) peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a) to reduce Abeta production through the inhibition of beta and gamma secretase enzymes and (b) to promote dissolution of existing cerebral Abeta plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Abeta signalling, particularly at the synapse. Abeta oligomers may cause aberrant N-methyl-D aspartate receptor (NMDAR) activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC). PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Abeta is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5). Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease. PMID- 26881139 TI - mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits. AB - We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20 21 days. MTEP (0.5-5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated. PMID- 26881136 TI - Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression. AB - Anxiety disorders (AnxDs) are highly prevalent throughout the lifespan, with detrimental effects on daily-life functioning, somatic health, and quality of life. An emerging perspective suggested that AnxDs may be associated with accelerated aging. In this paper, we explored the association between AnxDs and hallmarks of accelerated aging, with a specific focus on neuroprogression. We reviewed animal and human findings that suggest an overlap between processes of impaired neurogenesis, neurodegeneration, structural, functional, molecular, and cellular modifications in AnxDs, and aging. Although this research is at an early stage, our review suggests a link between anxiety and accelerated aging across multiple processes involved in neuroprogression. Brain structural and functional changes that accompany normal aging were more pronounced in subjects with AnxDs than in coevals without AnxDs, including reduced grey matter density, white matter alterations, impaired functional connectivity of large-scale brain networks, and poorer cognitive performance. Similarly, molecular correlates of brain aging, including telomere shortening, Abeta accumulation, and immune inflammatory and oxidative/nitrosative stress, were overrepresented in anxious subjects. No conclusions about causality or directionality between anxiety and accelerated aging can be drawn. Potential mechanisms of this association, limitations of the current research, and implications for treatments and future studies are discussed. PMID- 26881142 TI - An Unusual Case of Biatrial Myxoma in a Young Female. AB - Myxoma, a rare type of intracardiac tumor, forms a very small percentage of the cardiac cases. Reports of biatrial myxoma are rarer, with cases of single tumor reaching both atria being more common. Here, we present an unusual case of two independently growing atrial myxoma in a 29-year-old female. We emphasize that early recognition of symptoms, confirmation of diagnosis by transesophageal echocardiography, and prompt surgical excision remain vital in the management of such patients. The patient in the present case was managed successfully with no evidences of recurrence at the last follow-up. PMID- 26881140 TI - The Endocannabinoid System as a Therapeutic Target in Glaucoma. AB - Glaucoma is an irreversible blinding eye disease which produces progressive retinal ganglion cell (RGC) loss. Intraocular pressure (IOP) is currently the only modifiable risk factor, and lowering IOP results in reduced risk of progression of the disorder. The endocannabinoid system (ECS) has attracted considerable attention as a potential target for the treatment of glaucoma, largely due to the observed IOP lowering effects seen after administration of exogenous cannabinoids. However, recent evidence has suggested that modulation of the ECS may also be neuroprotective. This paper will review the use of cannabinoids in glaucoma, presenting pertinent information regarding the pathophysiology of glaucoma and how alterations in cannabinoid signalling may contribute to glaucoma pathology. Additionally, the mechanisms and potential for the use of cannabinoids and other novel agents that target the endocannabinoid system in the treatment of glaucoma will be discussed. PMID- 26881143 TI - Left Atrial Myxoma Hypervascularized from the Right Coronary Artery: An Interesting Cath Lab Finding. AB - Primary cardiac tumors are rare and approximately half of them are atrial myxomas. They rarely remain asymptomatic, especially if large. The imaging of a myxoma by contrast dye during coronary angiography is an infrequent sign, which clarifies the vascular supply of the tumor. We report herein an interesting and rare case of a left atrial myxoma hypervascularized from the right coronary artery. PMID- 26881141 TI - Synaptic Wnt/GSK3beta Signaling Hub in Autism. AB - Hundreds of genes have been associated with autism spectrum disorders (ASDs) and the interaction of weak and de novo variants derive from distinct autistic phenotypes thus making up the "spectrum." The convergence of these variants in networks of genes associated with synaptic function warrants the study of cell signaling pathways involved in the regulation of the synapse. The Wnt/beta catenin signaling pathway plays a central role in the development and regulation of the central nervous system and several genes belonging to the cascade have been genetically associated with ASDs. In the present paper, we review basic information regarding the role of Wnt/beta-catenin signaling in excitatory/inhibitory balance (E/I balance) through the regulation of pre- and postsynaptic compartments. Furthermore, we integrate information supporting the role of the glycogen synthase kinase 3beta (GSK3beta) in the onset/development of ASDs through direct modulation of Wnt/beta-catenin signaling. Finally, given GSK3beta activity as key modulator of synaptic plasticity, we explore the potential of this kinase as a therapeutic target for ASD. PMID- 26881144 TI - A Striking Coronary Artery Pattern in a Grown-Up Congenital Heart Disease Patient. AB - Left ventricular noncompaction (LVNC) is a myocardial disorder probably due to the arrest of normal embryogenesis of the left ventricle. It could be isolated or associated with other extracardiac and cardiac abnormalities, including coronary artery anomalies. Despite the continuous improvement of imaging resolution quality, this cardiomyopathy still remains frequently misdiagnosed, especially if associated with other heart diseases. We report a case of LVNC association with both malposition of the great arteries and a very original coronary artery pattern. PMID- 26881145 TI - Oral Myiasis Affecting Gingiva in a Child Patient: An Uncommon Case Report. AB - Certain dipteran flies larvae causing invasion of the tissues and organs of the humans or other vertebrates are called as myiasis, which feed on hosts dead or living tissues. It is well documented in the skin and hot climate regions; underdeveloped countries are affected more commonly. Oral cavity is affected rarely and it can be secondary to serious medical conditions. Poor oral hygiene, alcoholism, senility, or suppurating lesions can be associated with the oral myiasis. Inflammatory and allergic reactions are the commonest clinical manifestations of the disease. In the present case, gingiva of maxillary anterior region was affected by larval infection in a 13-year-old mentally retarded patient. PMID- 26881146 TI - A Rare Case of Concomitant Maxilla and Mandible Brown Tumours, Papillary Thyroid Carcinoma, Parathyroid Adenoma, and Osteitis Fibrosa Cystica. AB - Objective. The brown tumour of hyperparathyroidism is a result of a metabolic disorder caused by primary hyperparathyroidism. Report. We described a case of a 37-year-old female patient presenting bimaxillary intraoral lesions and swelling in the neck. Incisional biopsy of the oral lesion was performed and histopathological examination revealed a central giant cell lesion composed by intense haemorrhagic exudate, abundant presence of giant cells, and areas with hemosiderin pigment. The patient also presented high levels of serum calcium and parathyroid hormone, hyperfunctioning parathyroid tissue, bilateral parenchymal nephropathy, and densitometry lower than expected, showing an advanced stage of osteitis fibrosa cystica. Synchronous parathyroid adenoma and papillary thyroid carcinoma were confirmed by imaging exams and histopathologically. Conclusion. The composition of all the clinical, pathological, and imaging findings led to the final diagnosis of brown tumour of hyperparathyroidism. The occurrence of parathyroid adenoma, papillary thyroid carcinoma, and brown tumours of hyperparathyroidism in their late stage (osteitis fibrosa cystica) associated with oral brown tumours involving the mandible and maxilla is extremely rare. PMID- 26881147 TI - Direct Midline Diastema Closure with Composite Layering Technique: A One-Year Follow-Up. AB - Objective. Maxillary anterior spacing is a common aesthetic complaint of patients. Midline diastema has a multifactorial etiology such as labial frenulum, microdontia, mesiodens, peg-shaped lateral incisors, agenesis, cysts, habits such as finger sucking, tongue thrusting, or lip sucking, dental malformations, genetics, proclinations, dental-skeletal discrepancies, and imperfect coalescence of interdental septum. Appropriate technique and material for effective treatment are based on time, physical, psychological, and economical limitations. Direct composite resins in diastema cases allow dentist and patient complete control of these limitations and formation of natural smile. Clinical Considerations. In this case report a maxillary midline diastema was closed with direct composite resin restorations in one appointment without any preparation. One bottle total etch adhesive was used and translucent/opaque composite resin shades were layered on mesial surfaces of the teeth that were isolated with rubber dam and Teflon bands. Finishing and polishing procedures were achieved by using polishing discs. Patient was informed for recalls for every 6 months. Conclusions. At one-year recall no sensitivities, discolorations, or fractures were detected on teeth and restorations. Direct composite resins seemed to be highly aesthetic and durable restorations that can satisfy patients as under the conditions of case presented. PMID- 26881148 TI - A 27-Year-Old Severely Immunosuppressed Female with Misleading Clinical Features of Disseminated Cutaneous Sporotrichosis. AB - Sporotrichosis is a subacute or chronic granulomatous mycosis caused by fungus of the Sporothrix schenckii complex. It is considered to be a rare condition in most parts of the world. It mostly causes cutaneous infection but can also cause multisystemic disease. Unlike most deep cutaneous mycoses which have a primary pulmonary focus, it is usually caused by direct inoculation of the fungus into the skin causing a classical linear, lymphocutaneous nodular eruption. However, atypical presentations of the condition can occur especially in immunosuppressed individuals. We report the case of a severely immunosuppressed female who presented with disseminated cutaneous sporotrichosis which was initially diagnosed and treated as disseminated cutaneous Kaposi's sarcoma. PMID- 26881149 TI - Pentobarbital Toxicity after Self-Administration of Euthasol Veterinary Euthanasia Medication. AB - Suicide attempt via sodium pentobarbital is uncommon. A 48-year-old woman with a history of depression and prior suicide attempt was found unresponsive by her veterinarian spouse near a syringe containing pink solution. Upon EMS' arrival, the patient was experiencing apnea, hypoxemia, and miotic pupils; her blood glucose level measured 73 mg/dL. She was bradycardic and administered atropine with transient improvement in heart rate and transported to an emergency department; 2 mg of intravenous naloxone was administered without effect. She was endotracheally intubated via rapid sequence intubation. Rapid urine drug screening detected both benzodiazepines and barbiturates. The patient was transferred to an intensive care unit where she demonstrated a nearly absent radial pulse. Emergent fasciotomy to the left forearm and carpal tunnel was performed for acute compartment syndrome; "Euthasol" had been self-administered into the antecubital fossa. Expanded toxicological analysis via liquid chromatography/mass spectroscopy detected caffeine, atropine, 7-aminoclonazepam, phenytoin, citalopram, and naproxen. The patient's coma resolved over 48 hours and she was successfully extubated without complication. Emergency physicians must closely monitor patients exposed to veterinary euthanasia agents who develop central nervous system and respiratory depression, hypothermia, bradycardia, hypotension, or skin injury. Consultation with a regional poison center and medical toxicologist is recommended. PMID- 26881150 TI - Treatment of Ipilimumab Induced Graves' Disease in a Patient with Metastatic Melanoma. AB - Objective. Thyroid disease has been reported among the endocrinopathies that can occur after treatment with ipilimumab. Graves' disease, however, has been rarely reported with this medication. Here we report a case of Graves' disease diagnosed after initiation of ipilimumab in a patient with melanoma. Methods. We present the clinical presentation and management course of this patient followed by a related literature review. Results. A 67-year-old male with metastatic melanoma was started on ipilimumab. He developed hyperthyroidism after two doses of ipilimumab. The cause of hyperthyroidism was determined to be Graves' disease. Ipilimumab was held and the patient was started on methimazole with return to euthyroid status. Ipilimumab was resumed and the patient continued methimazole during the course of ipilimumab therapy, with controlled hyperthyroidism. Restaging studies following four cycles of ipilimumab showed complete response in the lungs, with residual melanoma in the neck. The patient then underwent total thyroidectomy and left neck dissection as a definitive treatment for both hyperthyroidism and residual melanoma. Conclusion. Graves' disease can develop after starting ipilimumab and methimazole can be an effective treatment. For patients whose hyperthyroidism is well-controlled on methimazole, ipilimumab may be resumed with close monitoring. PMID- 26881151 TI - Left Colon Diverticulitis Presenting as Perforated Lumbar Abscess: A Case Report and Review of the Current Literature. AB - Diverticular perforation is a common complication of diverticulitis and can lead to the creation of abscesses. The presence of such abscesses on the abdominal wall is rare and can lead to misdiagnosis. We present the case of a patient with abdominal pain and the formation of a large left lumbar abscess due to perforation of a diverticulum of the left colon and our surgical treatment of choice with favorable results. PMID- 26881152 TI - Protein Loosing Enteropathy Secondary to Strongyloidiasis: Case Report and Review of the Literature. AB - Strongyloidiasis is a helminthic disease which affects millions around the world resulting in a significant burden in certain high risk groups. It is rarely reported in the Lebanese population probably due to the low index of suspicion in common practice. We are reporting a case of strongyloidiasis that was found in an elderly patient presenting initially with dyspnea followed by skin rash, protein loosing enteropathy, diarrhea, and abdominal pain while on corticosteroid therapy. The diagnosis was suspected based on clinical presentation in addition to peripheral eosinophilia. We will also describe the upper and lower endoscopic aspects of the disease, as well as histologic findings on duodenal and colonic biopsies. PMID- 26881153 TI - Light Chain Escape in 3 Cases: Evidence of Intraclonal Heterogeneity in Multiple Myeloma from a Single Institution in Poland. AB - We report three cases of light chain escape (LCE) at a single institution in Poland, including an interesting case of biclonal monoclonal gammopathy of undetermined significance (MGUS) that satisfied the criteria for progression to light chain multiple myeloma (LCMM) with a rapid rise in serum free light chain (FLC) levels, following steroidal treatment for simultaneous temporal artery inflammation and polymyalgia rheumatica (PMR). In the three cases discussed, progression of the disease by light chain escape was associated with rapid and severe renal impairment, highlighting the necessity for prompt detection of such free light chain-only producing clones in order to prevent the possible development of irreversible end-organ damage. Interestingly, monitoring of these three patients by serum free light chain assay (sFLC) and retrospective heavy/light chain analysis (HLC) detected this clonal evolution prior to clinical relapse and suggests that these assays represent important additional tools for more accurate monitoring of multiple myeloma patients. PMID- 26881154 TI - Native Valve Streptococcus bovis Endocarditis and Refractory Transfusion Dependent Iron Deficiency Anaemia Associated with Concomitant Carcinoma of the Colon: A Case Report and Review of the Literature. AB - Streptococcus bovis is found as a commensal organism in human gut and may become opportunistically pathogenic. Infective endocarditis is one of the commonest modes of presentation of this infection. The association between Streptococcus bovis endocarditis and colorectal cancer is well recognized. We report a case of Streptococcus bovis endocarditis along with a refractory iron deficiency anaemia associated with concomitant carcinoma of ascending colon in a 63-year-old male. Cooccurrence of these two conditions may cause a challenge in the management. Considering the strong association of colon cancer with Streptococcus bovis endocarditis, a detailed screening colonoscopy is mandatory following the diagnosis of the latter. PMID- 26881155 TI - Angiographic Evidence of a Purely Pial Bihemispheric Intracranial Hemangiopericytoma. AB - Background. Classification of hemangiopericytoma (HPC) has evolved to a mesenchymal, nonmeningothelial grade two or three neoplasm according to the World Health Organization; however its blood supply has always been defined by dual origin, pial and dural contribution. Case Description. We present the case of a patient with an intracranial HPC with only pial vascular supply. Angiography confirmed the lack of dural supply to this bihemispheric intracranial mass. Subsequent histologic examination confirmed the diagnosis of hemangiopericytoma. Angiographic evidence here is atypical of the natural history of hemangiopericytomas with dual vascular supply and was critical in the decision making towards surgical resection without tumor embolization. Conclusion. Data presented suggests the lack of dural vascular supply alone does not rule out the diagnosis of hemangiopericytoma. PMID- 26881156 TI - Cognitive Impairments Preceding and Outlasting Autoimmune Limbic Encephalitis. AB - Mild cognitive impairment (MCI) can be the initial manifestation of autoimmune limbic encephalitis (ALE), a disorder that at times presents a diagnostic challenge. In addition to memory impairment, clinical features that might suggest this disorder include personality changes, agitation, insomnia, alterations of consciousness, and seizures. Once recognized, ALE typically responds to treatment with immune therapies, but long-term cognitive deficits may remain. We report two cases of patients with MCI who were ultimately diagnosed with ALE with antibodies against the voltage gated potassium channel complex. Months after apparent resolution of their encephalitides, both underwent neuropsychological testing, which demonstrated persistent cognitive deficits, primarily in the domains of memory and executive function, for cases 1 and 2, respectively. A brief review of the literature is included. PMID- 26881157 TI - Case with a Nonreassuring Fetal Status Induced by Massive Hematemesis due to Mallory-Weiss Tear That Required Emergency Cesarean Section at 38 Weeks' Gestation. AB - We describe a rare case of Mallory-Weiss tear with massive hematemesis at 38 weeks' gestation. A 35-year-old woman presented with epigastralgia followed by massive hematemesis. An emergency endoscopy indicated active pulsatile bleeding at the esophagocardial junction. Although an emergency endoscopic hemostasis was successful, late decelerations without acceleration on cardiotocogram were observed. Therefore, the patient underwent emergency cesarean section, along with blood transfusion, following the endoscopic hemostasis. The hemoglobin level just before the operation was 5.1 g/dL. We suspected that massive hematemesis induced maternal acute anemia and hypovolemia, which resulted in a nonreassuring fetal status. Hence, urgent endoscopic hemostasis, adequate blood transfusion, and emergency cesarean section were needed. Mallory-Weiss tear during the third trimester may have a possibility of massive hematemesis and urgent blood transfusion, emergency endoscopic hemostasis, and emergency cesarean section may be needed. PMID- 26881158 TI - Rare Case of Methemoglobinemia Complicating Pregnancy. AB - A patient at 38 weeks of gestation when taken for emergency cesarean section had her oxygen saturation of 66 to 70% (by saturation probe on monitor) in operation theatre. She was otherwise asymptomatic but her oxygen saturation was persistently low on the monitors. Her arterial blood gas analysis showed all parameters to be normal. Her electrocardiography was normal. Her surgery was imperative but due to her reduced oxygen saturation she became a high-risk case. In presence of senior consultants of anesthesia and gynecology and under high risk consent she had an uneventful cesarean delivery. Physician and cardiologist opinions were sought thereafter. The outcomes and the results of our efforts to find the etiology of her reduced saturation on monitors despite being clinically asymptomatic lead to the disclosure of this rare hemoglobinopathy. Mother and baby had uneventful course after delivery and were discharged well. PMID- 26881159 TI - Serous Macular Detachment Secondary to Optic Pit: Surgical Treatment and Long Time Results. AB - 32-year-old Turkish male patient presented with an optic disk pit and serous macular detachment in the left eye. Spectral domain optical coherence tomography revealed serous macular detachment and retinoschisis. After vitrectomy the retina gradually flattened and vision was gradually improved. We aimed to report a case of serous macula detachment secondary to optic pit and long term result of surgical treatment. PMID- 26881160 TI - Posterolateral Corner Reconstruction Alone Using a Fibular-Based Technique in a Patient with Persistent Unstable Revision Total Knee Arthroplasty. AB - Posterolateral rotatory instability is a relatively uncommon cause of unstable total knee arthroplasty (TKA). In most cases, surgical treatment requires revision TKA into a more constrained design or thicker polyethylene liner. We present a case of a patient with unstable TKA who remained unstable after increasing thickness of the polyethylene liner and undergoing more constrained TKA. After several revision surgeries, the patient was still unstable. Posterolateral corner reconstruction with a fibular-based technique using a tibialis anterior allograft was performed. At 1-year follow-up, the patient was stable and asymptomatic and with excellent function. A soft-tissue procedure only (fibular-based posterolateral corner reconstruction) can be effective at restoring posterolateral rotatory stability in a patient with persistent instability after revision TKA. PMID- 26881161 TI - Ossification of the Interosseous Membrane of the Leg in a Football Player: Case Report and Review of the Literature. AB - Introduction. We report a case of ossification of the interosseous membrane (OIM) of the leg in a football player who had no history of severe local traumas. A review of the literature of the OIM of the leg in athletes was also carried out. Case Report. A 38-year-old Caucasian male patient complained of pain on lateral aspect of the leg when playing football. Pain progressively worsened until he had to stop the sporting activity. Radiographs, and then CT and MRI, showed OIM in the middle third of the left leg. MRI showed inflammation of tibia periosteum and bone adjacent to the ossification, which was then excised. Two months after surgery the patient returned to play football. Conclusion. A thorough analysis of the literature revealed three types of OIM of the leg in athletes. Type I usually occurs after a syndesmosis ankle sprain, Type II appears to result from a tibia fracture, and Type III, of which only one fully recorded case has been published, is probably caused, as in our patient, by repetitive minor traumas to the leg. Awareness of the existence of Type III OIM can avoid erroneous diagnoses leading to useless investigations and treatments. PMID- 26881162 TI - Bilateral Neck of Femur Fractures in a Bilateral Below-Knee Amputee: A Unique Case. AB - According to the National Hip Fracture Database, over 64,000 patients were admitted with a hip fracture across England, Wales, and Northern Ireland in 2013, but very few are bilateral, and there are no current cases in the literature of bilateral neck of femur fractures in a patient with bilateral below-knee amputations. We present a case of a 69-year-old bilateral below-knee amputee male admitted to the emergency department with bilateral hip pain and radiological evidence of bilateral displaced neck of femur fractures. The patient subsequently underwent synchronous bilateral total hip replacements under general anaesthetic and an epidural and then went on to make a full recovery. He was discharged 27 days after arrival in hospital. Outpatient follow-up at 3 months has shown that the patient has returned to a similar level of preinjury function and is still able to carry out his daily activities with walking aids and bilateral leg prostheses. PMID- 26881163 TI - Auditory Cortical Maturation in a Child with Cochlear Implant: Analysis of Electrophysiological and Behavioral Measures. AB - The purpose of this study was to longitudinally assess the behavioral and electrophysiological hearing changes of a girl inserted in a CI program, who had bilateral profound sensorineural hearing loss and underwent surgery of cochlear implantation with electrode activation at 21 months of age. She was evaluated using the P1 component of Long Latency Auditory Evoked Potential (LLAEP); speech perception tests of the Glendonald Auditory Screening Procedure (GASP); Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS); and Meaningful Use of Speech Scales (MUSS). The study was conducted prior to activation and after three, nine, and 18 months of cochlear implant activation. The results of the LLAEP were compared with data from a hearing child matched by gender and chronological age. The results of the LLAEP of the child with cochlear implant showed gradual decrease in latency of the P1 component after auditory stimulation (172 ms-134 ms). In the GASP, IT-MAIS, and MUSS, gradual development of listening skills and oral language was observed. The values of the LLAEP of the hearing child were expected for chronological age (132 ms-128 ms). The use of different clinical instruments allow a better understanding of the auditory habilitation and rehabilitation process via CI. PMID- 26881164 TI - Septic Lateral Sinus Thrombosis: Sinus Exploration Is Unnecessary. AB - The algorithm of treatment of septic lateral sinus thrombosis (SLST) has undergone a paradigm shift with the understanding of the natural history of sigmoid sinus thrombosis. Thus, the recent medical literature promulgates the management of these cases with no sinus exploration. However, in view of marked paucity of literature on the cited subject, not much is known about this form of treatment. We present our experience of treating two paediatric cases of SLST with mastoid surgery and no sinus exploration: both cases had excellent recovery. Finally, conclusions are drawn in light of contemporary literature on this subject. PMID- 26881165 TI - Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas-Two Case Reports and Review of the Literature. AB - Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with squamous cell carcinoma in colon biopsies. After surgical resections, the carcinoma was proven to be the result of malignant transformation of ovarian mature cystic teratomas. Since squamous cell carcinoma of the colorectum is extremely rare, the presence of squamous cell carcinoma in a colonic biopsy in a female patient should alert the clinicians to other possible primary sites, as seen in these cases. PMID- 26881166 TI - Metastatic Chordoma: A Diagnostic Challenge on Fine Needle Aspiration. AB - Chordomas are primary low grade malignant tumors of bone that usually arise within both ends of axial skeleton. The Notochord is a midline, ectoderm-derived structure that defines the phylum of chordates. Chordomas may pose difficult diagnostic challenges when encountered in secondary locations, such as lungs or other parenchymatous organs. We report the cytologic findings of a metastatic chordoma sampled through CT-scan guided fine needle aspiration (FNA) of lower lobe lung nodule in a 54-year-old man diagnosed with recurrent chordoma involving the lumber spine and paraspinal region. PMID- 26881167 TI - Metachronous Occurrence of Granular Cell Tumor in Breast Skin and Scalp: Diagnostic Challenging Differentiating Benign from Malignant and a Literature Review. AB - Granular cell tumor (GCT) is a Schwann cell related benign neoplasm of soft tissue. GCT is an uncommon entity that occurs in a wide variety of body sites, but it is generally presented in the skin, oral cavity, superficial soft tissue, and respiratory and digestive tracts. Most of the GCTs are benign but clinically and radiologically these may mimic malignancy. Histopathological diagnosis is gold standard for establishing the true nature of the lesion. GCT is most commonly solitary but in about 10% of cases can be multifocal, usually involving various skin and soft tissue sites versus involving various internal sites. Therefore, these can involve skin and soft tissue or submucosa and viscera. GCT is usually benign; however, local recurrence is common due to incomplete removal. Malignant cases are rarely reported in 1-2% of cases. In this study, we report clinical and histopathological findings of a 36-year-old woman with metachronous GCT in breast and scalp. The clinical features raise the question of whether these are metachronous benign GCTs or whether this is establishment of malignant behavior. The aim of this report is to present the histopathological and clinical features of GCT and the diagnostic challenge of differentiating benign from malignant GCT. PMID- 26881168 TI - Trichohepatoenteric Syndrome or Syndromic Diarrhea-Report of Three Members in a Family, First Report from Iran. AB - Introduction. Intractable diarrhea of infancy (IDI) includes several types of early onset diarrhea; one of the rare etiologies is trichohepatoenteric (THE) syndrome, also known as syndromic diarrhea (SD) which was primarily described by Stankler et al. Hereby we report a family with several affected members which to our knowledge is the first case report from Iran. Report of Cases. A three-year old boy referred with short stature, poor weight gain, and intermittent steatotic diarrhea to our center. He was born to healthy, relative parents (cousins). He did not gain any weight after four months of age and began having intermittent steatotic diarrhea, abdominal distension, and fever. He was hospitalized several times. Two other children in the family also showed somewhat similar symptoms. Two sweat tests were negative for cystic fibrosis. Workup for Celiac disease was performed several times which was negative; however, gluten-free diet was tried several times which was not effective. Workup for Hirschsprung's disease was performed but colon was ganglionic. Evidence of liver involvement was approved by elevated liver enzymes and coarse echo of liver on sonography. Discussion. Trichoenterohepatic syndrome should be put in mind in cases of intractable diarrhea presenting in a family with several affected members. Early diagnosis would save patients from unnecessary workups. PMID- 26881169 TI - A Case of a 4-Year-Old Boy with a Mesenteric Chylous Cyst Infected with Histoplasma capsulatum. AB - Mesenteric cysts are uncommon entities and chyle- (lymph-) containing cysts are the rarest of this group. This is a case report of a 4-year-old boy with a mesenteric chylous cyst who was later found to have Histoplasma capsulatum infection. PMID- 26881170 TI - Intrathoracic Kidney after Blunt Abdominal Trauma: A Case Report and Review of the Literature. AB - Abdominal trauma is responsible for most genitourinary injuries. The incidence of renal artery injury and intrathoracic kidney is quite low in patients who present with blunt trauma experiencing damage. There are four defined etiologies for intrathoracic kidney, which include real intrathoracic ectopic kidney, eventration of the diaphragm, congenital diaphragmatic herniation, and traumatic diaphragmatic rupture. The traumatic intrathoracic kidney is an extremely rare case. We presented intrathoracic kidney case after traumatic posterior diaphragmatic rupture. PMID- 26881171 TI - Incidental Finding of a Rare Urachal Pathology: Urachal Mucinous Cystic Tumour of Low Malignant Potential. AB - Urachal mucinous cystic tumours are rare pathological findings with only 23 previously reported cases in the literature. We present the case of a 54-year-old man with an incidentally found urachal mucinous cystic tumour laparoscopically excised. With its known potential to cause pseudomyxoma peritonei, complete surgical excision is important. Long-term cystoscopic and radiological surveillance is also required. PMID- 26881172 TI - Diagnostic Yield of Echocardiography in Syncope Patients with Normal ECG. AB - Aim. This study aimed to assess the role of echocardiography as a diagnostic tool in evaluating syncope patients with normal versus abnormal electrocardiogram. Methods. We conducted a retrospective study of 468 patients who were admitted with syncope in 2011 at St. Joseph's Regional Medical Center, Paterson, NJ. Hospital records and patient charts, including initial emergency room history and physical, were carefully reviewed. Patients were separated into normal versus abnormal electrocardiogram groups and then further divided as normal versus abnormal echocardiogram groups. Causes of syncope were extrapolated after reviewing all test results and records of consultations. Results. Three hundred twelve of the total patients (68.6%) had normal ECG. Two-thirds of those patients had echocardiograms; 11 patients (5.7%) had abnormal echo results. Of the aforementioned patients, three patients had previous documented history of severe aortic stenosis on prior echocardiograms. The remaining eight had abnormal but nondiagnostic echocardiographic findings. Echocardiography was done in 93 of 147 patients with abnormal ECG (63.2%). Echo was abnormal in 27 patients (29%), and the findings were diagnostic in 6.5% patients. Conclusions. This study demonstrates that echocardiogram was not helpful in establishing a diagnosis of syncope in patients with normal ECG and normal physical examination. PMID- 26881173 TI - The Current Approach to Diagnosis and Management of Left Ventricular Noncompaction Cardiomyopathy: Review of the Literature. AB - Isolated left ventricular noncompaction (LVNC) is a genetic cardiomyopathy characterized by prominent ventricular trabeculations and deep intertrabecular recesses, or sinusoids, in communication with the left ventricular cavity. The low prevalence of patients with this cardiomyopathy presents a unique challenge for large, prospective trials to assess its pathogenesis, management, and outcomes. In this paper we review the embryology and genetics of LVNC, the diagnostic approach, and propose a management approach based on the current literature available. PMID- 26881174 TI - EOLA1 Inhibits Lipopolysaccharide-Induced Vascular Cell Adhesion Molecule-1 Expression by Association with MT2A in ECV304 Cells. AB - Our research group firstly discovered endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1, GenBank number AY074889) as a lipopolysaccharide (LPS) responsive gene in ECV304 cells. The previous studies have further demonstrated the association of EOLA1 with metallothionein 2A (MT2A), while the role of EOLA1 during LPS-induced inflammatory response in ECV304 cells is unknown. In this report, we determined the subcellular localization of EOLA1 and the regulatory capacity of EOLA1 on vascular cell adhesion molecule-1 (VCAM-1) in response to LPS in ECV304 cells. Our results show that EOLA1 is broadly diffuse in the cells, and EOLA1 expression is dramatically induced by LPS. EOLA1 knockdown results in significant enhancement of LPS-induced VCAM-1 production. Consistent with this, overexpression of EOLA1 leads to the reduction of LPS-induced VCAM-1 production. Furthermore, MT2A knockdown reduces LPS-induced VCAM-1 production. Collectively, our results demonstrate a negative regulatory role of EOLA1 on LPS-induced VCAM-1 expression involving its association with MT2A in ECV304 cells. PMID- 26881175 TI - Nicotine Inhibits Clostridium difficile Toxin A-Induced Colitis but Not Ileitis in Rats. AB - Nicotine is protective in ulcerative colitis but not Crohn's disease of the small intestine, but little is known about the effects of nicotine on Clostridium difficile toxin A-induced enteritis. Isolated ileal or colonic segments in anesthetized rats were pretreated with nicotine bitartrate or other pharmacological agents before intraluminal injection of toxin A. After 3 hours, the treated segments were removed and inflammation was assessed. Nicotine biphasically inhibited toxin A colitis but not ileitis. Pretreatment with the nicotinic receptor antagonist, hexamethonium, blocked the effects of nicotine. Pretreating the colonic segments with hexamethonium before toxin A administration resulted in more inflammation than seen with toxin A alone, suggesting that a tonic nicotinic anti-inflammatory condition exists in the colon. Nicotine also inhibited toxin A-induced increased colonic concentrations of the TRPV1 (transient receptor potential vanilloid subtype 1) agonist, leukotriene B4 (LTB4), and release of the proinflammatory neuropeptide, substance P. Pretreatment with nicotine did not protect against direct TRPV1-mediated colitis caused by intraluminal capsaicin. Nicotinic cholinergic receptors tonically protect the colon against inflammation and nicotine inhibits toxin A colitis but not toxin A ileitis in rats in part by inhibition of toxin A-induced activation of TRPV1 by endogenous TRPV1 agonists such as LTB4. PMID- 26881176 TI - The Effects of Noncompliance to Prolia (Denosumab) on the Changes in Bone Mineral Density: A Retrospective Review. AB - Although denosumab (Prolia) has been shown to be a safe and efficacious therapy for osteoporotic patients in numerous clinical trials, few studies have determined its effectiveness in real world clinical practice. A retrospective review of patients prescribed Prolia assessing the impact that noncompliance from the regular dosing regimen of six months for denosumab has on bone mineral density (BMD) was performed. 924 patient records were reviewed between August 2012 and September 2013 with 436 patients meeting the eligibility criteria. Patients were divided into three groups: subsequent injection of denosumab (1) less than five months, (2) between five and seven months, and (3) more than seven months after their initial subcutaneous injection. A multivariable regression analysis was conducted comparing the differences among the three prespecified groups in BMD change (g/cm(2)) after one year of denosumab therapy at both the lumbar spine (LS) and femoral neck (FN). The differences in LS and FN BMD have shown that the relationship between the timing of drug administration in these three groups and change in BMD over 1 year was not clinically or statistically significant (p > 0.05). A follow-up study with a larger sample size and longer follow-up duration is required to further characterize this relationship. PMID- 26881177 TI - Significance of TNF-alpha and the Adhesion Molecules: L-Selectin and VCAM-1 in Papillary Thyroid Carcinoma. AB - Circulating levels of TNF-alpha and the adhesion molecules L-Selectin and VCAM-1 as well as their expression in the primary tumors of patients with benign thyroid diseases and papillary thyroid carcinoma (PTC) have been determined in this study. The serum levels of TNF-alpha, L-Selectin, and VCAM-1 were significantly higher in patients with both benign thyroid diseases and PTC as compared to the healthy individuals. However, the levels of only TNF-alpha and L-Selectin, and not VCAM-1, were significantly higher in patients with PTC in comparison to those observed in patients with benign thyroid diseases. Further the expression of TNF alpha and L-Selectin was also significantly higher in the primary tumors of PTC patients, relative to the benign thyroid diseases. The expression of L-Selectin and VCAM-1 significantly correlated with aggressive tumor behavior. In PTC patients, the circulating TNF-alpha levels significantly positively correlated with the levels of L-Selectin, while TNF-alpha immunoreactivity was significantly associated with VCAM-1 expression. Serum TNF-alpha was found to be a significant prognosticator for OS in PTC patients. Overall the results signify that the interaction between TNF-alpha and the adhesion molecules may have a role in thyroid carcinogenesis and understanding this complexity may offer potential therapeutic targets for better management of thyroid cancer. PMID- 26881178 TI - Foetal Cell Transplantation for Parkinson's Disease: Focus on Graft-Induced Dyskinesia. AB - Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson's disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID. PMID- 26881179 TI - Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross Sectional Study. AB - Background. Patients with Parkinson's disease (PD) have a high risk of cognitive problems. Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism. Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson's disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up. Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems. Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies. PMID- 26881180 TI - Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model. AB - Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6 OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life. PMID- 26881181 TI - Clinical Pain and Neuropsychological Functioning in Parkinson's Disease: Are They Related? AB - Introduction. Pain is an important nonmotor symptom of Parkinson's disease (PD). Brain areas such as the hippocampus and the prefrontal cortex play an important role in the processing of pain. Since these brain areas are also involved in cognitive functioning, for example, episodic memory and executive functions, respectively, we examined whether a relationship exists between cognitive functioning and spontaneous pain in PD. Methods. Forty-eight patients with PD and 57 controls participated. Cognitive functioning was measured by a comprehensive battery of neuropsychological tests. Both the sensory-discriminative aspect and the motivational-affective aspect of pain were assessed. Multiple linear regression analyses were performed to assess a relation between cognition and pain. Results. Cognition was related to neither the sensory nor the affective aspect of pain in our sample of PD patients. Variance in pain measures was primarily explained by symptoms of depression and anxiety. Discussion. The difference between the affective and the sensory aspect of pain might be due to the neuropathology of PD, which is mainly present in areas processing the affective aspect of pain. Pain treatment might improve when mood is taken into account. We provide several explanations for the lack of an association between pain and cognition. PMID- 26881182 TI - Social Network Analysis of Cattle Movement in Sukhothai Province, Thailand: A Study to Improve Control Measurements. AB - The aim of this study is to analyse the pattern of cattle movement in Sukhothai province, Thailand. A validated questionnaire was applied to 308 respondents related to cattle farming using one-step snowball sampling. The results showed that most of the nodes are farmers who move their animals in the province. The average normalized degree centrality and normalized closeness centrality were low (<0.01 and 0.04, resp.). We found that traders are the nodes with a high value of centrality. This corresponds with the cutpoint analysis results that traders are outstanding. In conclusion, the relevant authorities should focus on the nodes such as traders for controlling disease. However, a measure to detect disease in the early stages needs to be implemented. PMID- 26881184 TI - Prevalence and Risk Factors Associated with Faecal Shedding of Cryptosporidium Oocysts in Dogs in the Federal Capital Territory, Abuja, Nigeria. AB - Cryptosporidium is one of the causes of diarrhoeal illness in man and animals worldwide. The aim of the study was to determine the prevalence and risk factors associated with faecal shedding of Cryptosporidium oocysts in dogs in FCT Abuja, Nigeria. A total of 276 dog faecal samples were examined using Modified Acid Fast (MAF) technique and Enzyme Linked Immunosorbent Assay (ELISA). Fifteen (5.4%) and 51 (18.5%) out of the 276 dog faecal samples examined were positive for Cryptosporidium oocysts and coproantigens, respectively. There was a fair agreement (0.371) between the two tests used in this study. The prevalence of Cryptosporidium infection was highest in 4 dogs (21.0%) between 3 and 9 months of age. Ten diarrhoeic dogs (30.3%) and 31 dogs from rural settlements were more infected (22.46%) with Cryptosporidium oocysts. There was statistical association between prevalence of Cryptosporidium and confinement of dogs (OR = 0.41; 95% CI on OR: 0.21 < OR < 0.80). However, there was no statistical association (P > 0.05) between prevalence of Cryptosporidium and age, diarrhoeic status of the dogs, sex, breed, and location. A total of 62.7% respondents did not have prior knowledge about dogs harbouring organisms that can infect humans. The finding of this research is of public health significance. PMID- 26881183 TI - Brazilian Spotted Fever with an Approach in Veterinary Medicine and One Health Perspective. AB - There is increasing interaction between man and pathogens transmitted by arthropods, especially by ticks. It is on this background that a holistic approach stands out, for the sake of Public Health. Brazilian Spotted Fever is an endemic disease at the country's southeast, with Amblyomma sculptum as its major contributor, followed by A. aureolatum and potentially Rhipicephalus sanguineus. Dogs have been considered sentinels, and in some areas the disease in dogs can precede human disease. Considering the importance of this disease for human health, the serological evidence in dogs, and the transmission of ticks between dogs and their owners, this review aimed to elucidate the importance of the epidemiological investigation, the diagnosis in dogs, and the role of veterinarians in Public Health to control vector-borne zoonotic diseases. We encourage veterinarians to include this rickettsial infection in the diagnosis of febrile diseases of common occurrence in dogs. PMID- 26881185 TI - Selective and Sensitive Detection of Cyanide Based on the Displacement Strategy Using a Water-Soluble Fluorescent Probe. AB - A water-soluble fluorescent probe (C-GGH) was used for the highly sensitive and selective detection of cyanide (CN(-)) in aqueous media based on the displacement strategy. Due to the presence of the recognition unit GGH (Gly-Gly-His), the probe C-GGH can coordinate with Cu(2+) and consequently display ON-OFF type fluorescence response. Furthermore, the in situ formed nonfluorescent C-GGH Cu(2+) complex can act as an effective OFF-ON type fluorescent probe for sensing CN(-) anion. Due to the strong binding affinity of CN(-) to Cu(2+), CN(-) can extract Cu(2+) from C-GGH-Cu(2+) complex, leading to the release of C-GGH and the recovery of fluorescent emission of the system. The probe C-GGH-Cu(2+) allowed detection of CN(-) in aqueous solution with a LOD (limit of detection) of 0.017 MUmol/L which is much lower than the maximum contaminant level (1.9 MUmol/L) for CN(-) in drinking water set by the WHO (World Health Organization). The probe also displayed excellent specificity for CN(-) towards other anions, including F( ), Cl(-), Br(-), I(-), SCN(-), PO4 (3-), N3 (-), NO3 (-), AcO(-), SO4 (2-), and CO3 (2-). PMID- 26881186 TI - Dispersive Liquid-Liquid Microextraction of Bismuth in Various Samples and Determination by Flame Atomic Absorption Spectrometry. AB - A dispersive liquid-liquid microextraction method for the determination of bismuth in various samples by flame atomic absorption spectrometry is described. In this method, crystal violet was used as counter positive ion for BiCl4 (-) complex ion, chloroform as extraction solvent, and ethanol as disperser solvent. The analytical parameters that may affect the extraction efficiency like acidity of sample, type and amount of extraction and disperser solvents, amount of ligand, and extraction time were studied in detail. The effect of interfering ions on the analyte recovery was also investigated. The calibration graph was linear in the range of 0.040-1.00 mg L(-1) with detection limit of 4.0 MUg L(-1) (n = 13). The precision as relative standard deviation was 3% (n = 11, 0.20 mg L( 1)) and the enrichment factor was 74. The developed method was applied successfully for the determination of bismuth in various water, pharmaceutical, and cosmetic samples and the certified reference material (TMDA-64 lake water). PMID- 26881187 TI - Primary Lymphoepithelioma-Like Carcinoma of the Prostate Gland: A Review of the Literature. AB - Background. Primary lymphoepithelioma-like carcinoma of the prostate gland (PLELCP) is rare with hardly any information on its diagnostic features and biological behaviour. Aim. To review the literature. Method. Various Internet data bases were searched. Literature Review. PLELCP is extremely rare and there are hardly any pictures of the tumour involving the prostate; hence it would appear that clinicians would need to use their knowledge of the microscopic and immunohistochemical characteristics of the tumour in the nasopharynx and urinary bladder as diagnostic aid. PLELCP on microscopy mimics nasopharyngeal LELC. The LELC component of the tumour is characterized by indistinct cytoplasmic borders and a syncytial growth pattern. The stroma may be densely infiltrated by lymphoid cells admixed with some plasma cells and neutrophils and at times prominent infiltration of eosinophils. PLELCPs tend to have adenocarcinoma, either as the only pattern or with additional ductal components or adenosquamous carcinoma. PLELCPs stain positively with PSA, PSAP, AMACR/P504S, EMA, and cytokeratins AE1/AE3, 7, 8, and 20. There is no consensus on treatment of PLECP. The reported prognosis has been poor. Conclusions. PLELCPs should be entered into a multicenter trial to determine the biological behaviour and to find the best treatment option that would improve the prognosis. PMID- 26881189 TI - Stroke and sleep-disordered breathing: A relationship under construction. AB - The association between sleep-disordered breathing (SDB) and cardiovascular risk has been the focus of attention in recent years. Sleep disorders are emerging risk factors for cardiovascular disease and have been related to the whole spectrum of stroke, including transient ischemic attack, ischemic cerebral infarction and intracerebral haemorrhage. It has been shown that lacunar stroke or lacunar infarctions affecting the internal capsule or the protuberance are associated with a higher frequency of SDB. Acute stroke patients with associated SDB have a worse prognosis and a higher mortality as compared to patients with first-ever stroke without SDB. Preliminary studies provide evidence of the usefulness of treatment with continuous positive airway pressure when SDB is present in stroke patients. PMID- 26881188 TI - Visual Working Memory in Human Cortex. AB - Visual working memory (VWM) is the ability to maintain visual information in a readily available and easily updated state. Converging evidence has revealed that VWM capacity is limited by the number of maintained objects, which is about 3 - 4 for the average human. Recent work suggests that VWM capacity is also limited by the resolution required to maintain objects, which is tied to the objects' inherent complexity. Electroencephalogram (EEG) studies using the Contralateral Delay Activity (CDA) paradigm have revealed that cortical representations of VWM are at a minimum loosely organized like the primary visual system, such that the left side of space is represented in the right hemisphere, and vice versa. Recent functional magnetic resonance imaging (fMRI) work shows that the number of objects is maintained by representations in the inferior intraparietal sulcus (IPS) along dorsal parietal cortex, whereas the resolution of these maintained objects is subserved by the superior IPS and the lateral occipital complex (LOC). These areas overlap with recently-discovered, retinotopically-organized visual field maps (VFMs) spanning the IPS (IPS-0/1/2/3/4/5), and potentially maps in lateral occipital cortex, such as LO-1/2, and/or TO-1/2 (hMT+). Other fMRI studies have implicated early VFMs in posterior occipital cortex, suggesting that visual areas V1-hV4 are recruited to represent information in VWM. Insight into whether and how these VFMs subserve VWM may illuminate the nature of VWM. In addition, understanding the nature of these maps may allow a greater investigation into individual differences among subjects and even between hemispheres within subjects. PMID- 26881192 TI - Black esophagus syndrome associated with diabetic ketoacidosis. AB - Acute esophageal necrosis, also known as "black esophagus syndrome", is a rare acute esophageal disease that is often associated with vomiting and upper gastrointestinal haemorrhage. At present, little is known regarding the pathogenesis of this disease. We present the case of a 50-year-old white male patient with diabetic ketoacidosis suffering from acute esophageal necrosis with nausea and vomiting but without any clinical signs of upper gastrointestinal bleeding. PMID- 26881190 TI - Cytopathologic diagnosis of fine needle aspiration biopsies of thyroid nodules. AB - Fine-needle aspiration (FNA) cytology is an important diagnostic tool in patients with thyroid lesions. Several systems have been proposed for the cyropathologic diagnosis of the thyroid nodules. However cases with indeterminate cytological findings still remain a matter of debate. In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules. A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors' perspective. The main purpose of thyroid FNA is to identify patients with higher risk for malignancy, and to prevent unnecessary surgeries for benign conditions. The Bethesda System for Reporting Thyroid Cytopathology is the most widely used system for the diagnosis of thyroid FNA specimens. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. In conclusion, patients who require repeated FNAs for indeterminate diagnoses will be resolved by repeat FNA in a percentage of 72% 80%. PMID- 26881193 TI - Herpes simplex induced necrotizing tonsillitis in an immunocompromised patient with ulcerative colitis. AB - We here present the case of a 22-year-old female of Suriname ethnicity with ulcerative colitis who received treatment with mercaptopurine and infliximab. She presented herself with a severe necrotizing tonsillitis due to herpes simplex virus type-1 (HSV-1). Combination therapy consisting of immunomodulators and anti tumor necrosis factor (TNF) agents is increasingly being used. Anti-TNF therapy is associated with an increased risk of developing serious infections, and especially patients receiving combination treatment with thiopurines are at an increased risk. We here show that HSV infections can cause a severe tonsillitis in immunocompromised patients. Early recognition is essential when there is no improvement with initial antibiotic therapy within the first 24 to 72 h. HSV infections should be in the differential diagnosis of immunocompromised patients presenting with a necrotizing tonsillitis and can be confirmed by polymerase chain reaction. Early treatment with antiviral agents should be considered especially if antibiotic treatment fails in such patients. PMID- 26881191 TI - Safety and efficacy of anti-tumor necrosis factors alpha in patients with psoriasis and chronic hepatitis C. AB - Up to date, in literature, it is still debated the role of anti-tumor necrosis factors (TNF)-alpha treatments in hepatitis C virus (HCV) patients. TNF-alpha performs a lot of functions, it is an important pro-inflammatory cytokine and it is involved in the host's immunity. Since TNF-alpha is implicated in the apoptotic signaling pathway of hepatocytes infected by HCV, anti TNF-alpha therapy may increase the risk of viral replication or their reactivation. However the treatment of anti TNF-alpha could have a healthful role because TNF-alpha appears to be engaged in the pathogenesis of liver fibrosis, inducing apoptotic pathways. We describe the case of a patient with plaque-type psoriasis and concomitant chronic HCV, who was treated successfully with anti-TNF agents simultaneously to cyclosporine without sign of reactivation of HCV and increase of liver enzymes. Our personal experience shows that anti-TNF-alpha agents are not only effective but also safe. Furthermore the combination therapy of cyclosporine and anti-TNF-alpha appears to be well-tolerated and able to reduce the amount of liver enzymes as well as HCV-viral-load. However systematic, large scale studies with long follow-ups will be needed to confirm our results, in association with close liver function monitoring. PMID- 26881194 TI - Plant Comparative and Functional Genomics. PMID- 26881195 TI - Transcriptome Profile of the Asian Giant Hornet (Vespa mandarinia) Using Illumina HiSeq 4000 Sequencing: De Novo Assembly, Functional Annotation, and Discovery of SSR Markers. AB - Vespa mandarinia found in the forests of East Asia, including Korea, occupies the highest rank in the arthropod food web within its geographical range. It serves as a source of nutrition in the form of Vespa amino acid mixture and is listed as a threatened species, although no conservation measures have been implemented. Here, we performed de novo assembly of the V. mandarinia transcriptome by Illumina HiSeq 4000 sequencing. Over 60 million raw reads and 59,184,811 clean reads were obtained. After assembly, a total of 66,837 unigenes were clustered, 40,887, 44,455, and 22,390 of which showed homologous matches against the PANM, Unigene, and KOG databases, respectively. A total of 15,675 unigenes were assigned to Gene Ontology terms, and 5,132 unigenes were mapped to 115 KEGG pathways. The zinc finger domain (C2H2-like), serine/threonine/dual specificity protein kinase domain, and RNA recognition motif domain were among the top InterProScan domains predicted for V. mandarinia sequences. Among the unigenes, we identified 534,922 cDNA simple sequence repeats as potential markers. This is the first transcriptomic analysis of the wasp V. mandarinia using Illumina HiSeq 4000. The obtained datasets should promote the search for new genes to understand the physiological attributes of this wasp. PMID- 26881196 TI - A Validated TLC-Densitometric Method for the Determination of Mesterolone in Bulk Material and in Tablets. AB - Mesterolone is a synthetic androgenic steroid indicating a weak anabolic activity. A new, simple in use, and economical TLC-densitometric method in normal phase system (NP-TLC) has been developed and validated for the identification and quantitative determination of mesterolone in bulk drug and in tablet formulation. NP-TLC analysis was performed on aluminium plates precoated with silica gel 60F254 as the stationary phase using chloroform-acetone (40 : 10, v/v) as mobile phase. Densitometric analysis was carried out at lambda = 745 nm after staining with phosphomolybdic acid. These conditions were found to give visible (dark blue) spot and sharp peak, respectively, for mesterolone at R F 0.75 +/- 0.02 and enabled satisfactory separation of mesterolone from its related substance (potential impurity). The proposed NP-TLC-densitometric method was validated for specificity, linearity, precision, accuracy, robustness, and sensitivity according to ICH guideline and other validation requirements. The limit of detection (LOD) and limit of quantification (LOQ) were 61.0 ng . spot(-1) and 184.0 ng . spot(-1), respectively. The percent content of mesterolone in marketed tablet formulation was found to be 99.40% of label claim. The developed TLC densitometric method can be successfully used in quality control of mesterolone in bulk material and also tablet formulation. PMID- 26881197 TI - Spinal Motion Preservation Surgery. PMID- 26881198 TI - Effect of Air-Polishing on Titanium Surfaces, Biofilm Removal, and Biocompatibility: A Pilot Study. AB - PURPOSE: The aims of this in vitro study were to evaluate morphological changes induced by glycine powder air-polishing on titanium surfaces, biofilm removal, and biocompatibility. MATERIAL AND METHODS: Titanium grade IV discs were allocated into two groups: (1) discs without biofilm and (2) discs for Streptococcus mutans biofilm formation. Discs in each group were further subdivided into (a) no treatment and (b) air-polishing treatment with glycine powder. Discs were characterized by scanning electron microscopy (SEM), electron dispersive spectroscopy (EDS), and confocal microscopy. Bacterial biofilms were quantified using a crystal violet dye-binding assay. Biocompatibility was evaluated by measuring the coverage and viability of L929 fibroblast cells cultured on the discs. RESULTS: Air-polishing increased the roughness of treated discs (P < 0.05). EDS analysis did not show significant differences in the chemical composition of treated and nontreated discs. The amount of residual biofilm on treated discs was 8.6-fold lower than untreated controls (P < 0.05). Coverage of treated discs by fibroblasts was half that of untreated discs (P < 0.05) although both groups had the same cell viability. CONCLUSIONS: Air polishing removed a significant amount of biofilm from titanium surfaces. The "polishing" was accompanied by increased surface roughness, but there were no changes in chemical and elemental compositions, nor the biocompatibility. PMID- 26881199 TI - Impact of Fibrotic Tissue on Shear Wave Velocity in Thyroid: An Ex Vivo Study with Fresh Thyroid Specimens. AB - We sought to elucidate the correlation between shear wave velocity (SWV) and fibrosis in thyroid by precisely assessing pathological structures inside 5 * 5 mm(2) regions of interest (ROIs) of resected specimens, under conditions that excluded physical artifacts. The materials were unselected thyroid and lymph node specimens resected during thyroid surgery. Immediately after surgery, fresh unfixed thyroid and metastatic lymph node specimens were suspended in gel phantoms, and SWV was measured. Upon pathological examination of each specimen, the extent of fibrosis was graded as none, moderate, or severe. A total of 109 specimens were evaluated: 15 normal thyroid, 16 autoimmune thyroiditis, 40 malignant nodules, 19 benign thyroid nodules, and 19 metastatic lymph nodes. When all specimens were classified according to the degree of fibrosis determined by pathological imaging, the mean SWV was 1.49 +/- 0.39 m/s for no fibrosis, 2.13 +/ 0.66 m/s for moderate fibrosis, and 2.68 +/- 0.82 m/s for severe fibrosis. The SWVs of samples with moderate and severe fibrosis were significantly higher than those of samples without fibrosis. The results of this study demonstrate that fibrosis plays an important role in determining stiffness, as measured by SWV in thyroid. PMID- 26881200 TI - Assessment of Random Error in Phantom Dosimetry with the Use of Error Simulation in Statistical Software. AB - OBJECTIVE: To investigate if software simulation is practical for quantifying random error (RE) in phantom dosimetry. MATERIALS AND METHODS: We applied software error simulation to an existing dosimetry study. The specifications and the measurement values of this study were brought into the software (R version 3.0.2) together with the algorithm of the calculation of the effective dose (E). Four sources of RE were specified: (1) the calibration factor; (2) the background radiation correction; (3) the read-out process of the dosimeters; and (4) the fluctuation of the X-ray generator. RESULTS: The amount of RE introduced by these sources was calculated on the basis of the experimental values and the mathematical rules of error propagation. The software repeated the calculations of E multiple times (n = 10,000) while attributing the applicable RE to the experimental values. A distribution of E emerged as a confidence interval around an expected value. CONCLUSIONS: Credible confidence intervals around E in phantom dose studies can be calculated by using software modelling of the experiment. With credible confidence intervals, the statistical significance of differences between protocols can be substantiated or rejected. This modelling software can also be used for a power analysis when planning phantom dose experiments. PMID- 26881201 TI - Minimally Invasive Techniques to Accelerate the Orthodontic Tooth Movement: A Systematic Review of Animal Studies. AB - OBJECTIVE: To evaluate various noninvasive and minimally invasive procedures for the enhancement of orthodontic tooth movement in animals. MATERIALS AND METHODS: Literature was searched using NCBI (PubMed, PubMed Central, and PubMed Health), MedPilot (Medline, Catalogue ZB MED, Catalogue Medicine Health, and Excerpta Medica Database (EMBASE)), and Google Scholar from January 2009 till 31 December 2014. We included original articles related to noninvasive and minimally invasive procedures to enhance orthodontic tooth movement in animals. Extraction of data and quality assessments were carried out by two observers independently. RESULTS: The total number of hits was 9195 out of which just 11 fulfilled the inclusion criteria. Nine articles were good and 5 articles were moderate in quality. Low level laser therapy (LLLT) was among the most common noninvasive techniques whereas flapless corticision using various instruments was among the commonest minimally invasive procedures to enhance velocity of tooth movement. CONCLUSIONS: LLLT, low intensity pulsed ultrasound (LIPUS), mechanical vibration, and flapless corticision are emerging noninvasive and minimally invasive techniques which need further researches to establish protocols to use them clinically with conviction. PMID- 26881202 TI - Contrast-Enhanced Ultrasonography Features of Breast Malignancies with Different Sizes: Correlation with Prognostic Factors. AB - This study was to investigate the correlation between contrast-enhanced ultrasonography (CEUS) characteristics with prognostic factors in breast cancers with different sizes. A retrospective analysis of CEUS characteristics of 104 pathologically proven malignant lesions from 104 women was conducted. Lesions were divided into two groups according to their size measured by US (Group 1: maximum diameter <=20 mm; Group 2: maximum diameter >20 mm). Features including enhancement degree, order and pattern, enlargement of the enhancement area, and penetrating vessels on CEUS were evaluated. Pathologic prognostic factors, including estrogen and progesterone receptor status, and the expression of c-erb B2, p53, Ki-67, and VEGF were assessed. Comparison of enhancement pattern parameters between Group 1 and Group 2 showed statistically significant differences (P < 0.0001). A significant correlation was found between enlargement of the enhancement area and ER positivity in Group 1 (P = 0.032). In Group 2 the absence of penetrating vessels was significantly associated with VEGF negativity (P = 0.022) and ER negativity (P = 0.022). Centripetal enhancement reflected VEGF negativity (P = 0.033) in lesions with diameter >20 mm. Thus, breast cancers with different sizes show different CEUS features; small breast cancers show homogeneous enhancement pattern while cancers with diameter >20 mm show homogeneous enhancement pattern. Some CEUS characteristics of differently sized breast cancers could be correlated with prognostic factors, which may be useful in prognosis assessment. PMID- 26881203 TI - Enhanced and Secretory Expression of Human Granulocyte Colony Stimulating Factor by Bacillus subtilis SCK6. AB - This study describes a simplified approach for enhanced expression and secretion of a pharmaceutically important human cytokine, that is, granulocyte colony stimulating factor (GCSF), in the culture supernatant of Bacillus subtilis SCK6 cells. Codon optimized GCSF and pNWPH vector containing SpymwC signal sequence were amplified by prolonged overlap extension PCR to generate multimeric plasmid DNA, which was used directly to transform B. subtilis SCK6 supercompetent cells. Expression of GCSF was monitored in the culture supernatant for 120 hours. The highest expression, which corresponded to 17% of the total secretory protein, was observed at 72 hours of growth. Following ammonium sulphate precipitation, GCSF was purified to near homogeneity by fast protein liquid chromatography on a QFF anion exchange column. Circular dichroism spectroscopic analysis showed that the secondary structure contents of the purified GCSF are similar to the commercially available GCSF. Biological activity, as revealed by the regeneration of neutrophils in mice treated with ifosfamine, was also similar to the commercial preparation of GCSF. This, to our knowledge, is the first study that reports secretory expression of human GCSF in B. subtilis SCK6 with final recovery of up to 96 mg/L of the culture supernatant, without involvement of any chemical inducer. PMID- 26881204 TI - MyD88 Polymorphisms and Association with Susceptibility to Salmonella Pullorum. AB - Myeloid differentiation primary response gene 88 (MYD88), a universal adapter protein, plays an important role in activating the nuclear factor-kappaB (NF kappaB) and regulating the expression of proinflammatory genes like tumor necrosis factor (TNF) and interleukin-1 (IL-1), which were highly involved in Salmonella Pullorum infection. To detect the relationship between polymorphisms of the MyD88 gene and Salmonella Pullorum disease, we screened the coding region (CDS) of the MYD88 gene by DNA pool construction and sequencing based on case control study. Eight single nucleotide polymorphisms (SNPs) in the sequenced fragment (5 exons), 7 known loci and one novel mutation named G4810372T (SNP8), were found in the fifth exon. In addition, we found 7 nonsynonymous substitutions. The allele frequency of only one SNP, g.4810191C > T (SNP1), was significantly different (P < 0.05) between case and control groups. The genotype frequencies of SNP1 (g.4810191C > T) and SNP3 (g.4810257G > T) were of significant difference between the case and the control groups (P < 0.05). Collectively, SNPs of the MyD88 gene were significantly associated with susceptibility to Salmonella Pullorum infection, which can be used as a disease resistant marker in chicken. These results provided a theoretical basis for future research on chicken breeding by marker-assisted selection. PMID- 26881205 TI - Vascular Endothelial Growth Factor Is Associated with the Morphologic and Functional Parameters in Patients with Hypertrophic Cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is mostly autosomal dominant disease of the myocardium, which is characterized by myocardial hypertrophy. Vascular endothelial growth factor (VEGF) is involved in myocyte function, growth, and survival. The aim of study was to analyze the clinical significance of VEGF in structural and functional changes in patient with HCM. METHODS: In a group of 21 patients with nonobstructive HCM, we assessed serum VEGF and analyzed its association with morphological and functional parameters. Compared to healthy controls, serum VEGF was increased: 199 (IQR: 120.4-260.8) ng/L versus 20 (IQR: 14.8-37.7) ng/L, P < 0.001. VEGF levels were associated with left atrium diameter (r = 0.51, P = 0.01), left ventricle ejection fraction (r = -0.56, P = 0.01), fractional shortening (r = -0.54, P = 0.02), left ventricular mass (r = 0.61, P = 0.03), LV mass index (r = 0.46, P = 0.04), vena cava inferior diameter (r = 0.65, P = 0.01), and peak gradient of tricuspid regurgitation (r = 0.46, P = 0.03). CONCLUSIONS: Increased VEGF level is associated with structural and functional parameters in patients with HCM and serves as a potential tool for diagnostic process of these patients. PMID- 26881206 TI - Computational Analysis of the Binding Specificities of PH Domains. AB - Pleckstrin homology (PH) domains share low sequence identities but extremely conserved structures. They have been found in many proteins for cellular signal dependent membrane targeting by binding inositol phosphates to perform different physiological functions. In order to understand the sequence-structure relationship and binding specificities of PH domains, quantum mechanical (QM) calculations and sequence-based combined with structure-based binding analysis were employed in our research. In the structural aspect, the binding specificities were shown to correlate with the hydropathy characteristics of PH domains and electrostatic properties of the bound inositol phosphates. By comparing these structure properties with sequence-based profiles of physicochemical properties, PH domains can be classified into four functional subgroups according to their binding specificities and affinities to inositol phosphates. The method not only provides a simple and practical paradigm to predict binding specificities for functional genomic research but also gives new insight into the understanding of the basis of diseases with respect to PH domain structures. PMID- 26881207 TI - Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats. AB - The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 MUL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 MUL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra articular 0.5% bupivacaine (10 and 20 MUL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 MUL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 MUL had a significant analgesic effect for 2 days, even though T-gel at 50 MUL further reduced the weight load, demonstrating that intra articular T-gel (20 MUL) has long-lasting analgesic effects in OA rats. Thus, T gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID- 26881208 TI - Treatment of Endometriosis with the GnRHa Deslorelin and Add-Back Estradiol and Supplementary Testosterone. AB - BACKGROUND: This randomized, multicenter, open-label clinical trial was intended to generate pilot data on the efficacy and safety of the gonadotropin-releasing hormone agonist (GnRHa) deslorelin (D) with low-dose estradiol +/- testosterone (E2 +/- T) add-back for endometriosis-related pelvic pain. METHODS: Women with pelvic pain and laparoscopically confirmed endometriosis were treated with a six month course of daily intranasal D with concurrent administration of either transdermal E2, intranasal E2, or intranasal E2 + T. Efficacy data included evaluation of dyspareunia, dysmenorrhea, pelvic pain, tenderness, and induration. Cognition and quality of life were also assessed. Safety parameters included assessment of endometrial hyperplasia, bone mineral density (BMD), and hot flashes. RESULTS: Endometriosis symptoms and signs scores decreased in all treatment arms from a baseline average of 7.4 to 2.5 after 3 months of treatment and 3.4 after 6 months. BMD changes and incidence of hot flashes were minimal, and no endometrial hyperplasia was observed. Patient-reported outcomes showed significant improvement across multiple domains. CONCLUSIONS: Daily intranasal D with low dose E2 +/- T add-back resulted in significant reduction in severity of endometriosis symptoms and signs with few safety signals and minimal hypoestrogenic symptoms that would be expected with the use of a GnRHa alone. PMID- 26881209 TI - Fuzheng Huayu Recipe Ameliorates Liver Fibrosis by Restoring Balance between Epithelial-to-Mesenchymal Transition and Mesenchymal-to-Epithelial Transition in Hepatic Stellate Cells. AB - Activation of hepatic stellate cells (HSCs) depending on epithelial-to mesenchymal transition (EMT) reflects the key event of liver fibrosis. Contrastively, mesenchymal-to-epithelial transition (MET) of HSCs facilitates the fibrosis resolution. Here we investigated the effect of Fuzheng Huayu (FZHY) recipe, a Chinese herbal decoction made of Radix Salviae Miltiorrhizae, Semen Persicae, Cordyceps sinensis, Pollen Pini, and Gynostemma pentaphyllum, on liver fibrosis concerning the balance of EMT and MET in HSCs. In contrast to the increased TGF-beta 1/BMP-7 ratio in activated HSCs, FZHY administration induced significant upregulation of BMP-7 and downregulation of TGF-beta 1 at both transcription and translation levels. Restoration of TGF-beta 1/BMP-7 ratio inhibited the expression of p38 MAPK and phosphorylated p38 MAPK, resulting in the reversal of epithelial-to-mesenchymal transition (EMT) to mesenchymal-to epithelial transition (MET) as characterized by the abolishment of EMT markers (alpha-SMA and desmin) and reoccurrence of MET marker (E-cadherin). In vivo treatment of FZHY recipe also demonstrated the statistical reduction of activated HSCs with EMT phenotype, which attenuated the carbon tetrachloride- (CCl4-) induced liver fibrosis in a dose-dependent manner. These findings may highlight a novel antifibrotic role of FZHY recipe on the basis of rebalancing EMT and MET in HSCs. PMID- 26881210 TI - The Effect of Femoral Cutting Guide Design Improvements for Patient-Specific Instruments. AB - Although the application of patient-specific instruments (PSI) for total knee arthroplasty (TKA) increases the cost of the surgical procedure, PSI may reduce operative time and improve implant alignment, which could reduce the number of revision surgeries. We report our experience with TKA using PSI techniques in 120 patients from March to December 2014. PSI for TKA were created from data provided by computed tomography (CT) scans or magnetic resonance imaging (MRI); which imaging technology is more reliable for the PSI technique remains unclear. In the first 20 patients, the accuracy of bone resection and PSI stability were compared between CT and MRI scans with presurgical results as a reference; MRI produced better results. In the second and third groups, each with 50 patients, the results of bone resection and stability were compared in MRI scans with respect to the quality of scanning due to motion artifacts and experienced know-how in PSI design, respectively. The optimized femoral cutting guide design for PSI showed the closest outcomes in bone resection and PSI stability with presurgical data. It is expected that this design could be a reasonable guideline in PSI. PMID- 26881212 TI - Erratum to "Need for Scientific Rigor in the Evaluation of Minimally Invasive Alternative Procedures". PMID- 26881211 TI - CTA Characteristics of the Circle of Willis and Intracranial Aneurysm in a Chinese Crowd with Family History of Stroke. AB - BACKGROUND AND PURPOSE: The vascular morphology in crowd with family history of stroke remains unclear. The present study clarified the characteristics of the intracranial vascular CoW and prevalence of intracranial aneurysms in subjects with family history of stroke. METHODS: A stratified cluster, random sampling method was used for subjects with family history of stroke among rural residents in Jixian, Tianjin, China. All the subjects underwent a physical examination, head computed tomography (CT) scan, and cephalic and cervical computed tomography angiography (CTA) scan. Anatomic variations in the Circle of Willis and cerebrovascular disease in this population were analyzed. RESULTS: In the crowd with similar living environment, stable genetic background, and family history of stroke and without obvious nerve function impairment (1) hypoplasia or absence of A1 segment was significantly different in gender (male versus female: 9.8% versus 18.8%, p = 0.031), especially the right-side A1 (male versus female: 5.9% versus 16.4%, p = 0.004). (2) Hypoplasia or absence of bilateral posterior communicating arteries was more common in men than women (58.2% versus 45.3%, p = 0.032). Unilateral fetal posterior cerebral artery was observed more often in women than men (17.2% versus 8.5%, p = 0.028). (3) The percentage of subjects with incomplete CoW did not increase significantly with age. Compared to healthy Chinese people, the crowd had a higher percentage of incomplete CoW (p < 0.001). (4) No obvious correlation between risk factors and CoW was found. (5) The prevalence of aneurysm was 10.3% in the special crowd. CONCLUSIONS: The certain variations of CoW showed significant relation to gender, but not to age in people with family history of stroke. The incomplete circle may be a dangerous factor that is independent of common risk factors for stroke and tend to lead to cerebral ischemia in the crowd with family history of stroke. The prevalence of intracranial aneurysm is comparatively high in the present subjects compared to other people. PMID- 26881214 TI - Advances and Controversies in Perioperative Airway Management. PMID- 26881213 TI - Effects of Tetrahydrocurcumin on Tumor Growth and Cellular Signaling in Cervical Cancer Xenografts in Nude Mice. AB - Tetrahydrocurcumin (THC) is a stable metabolite of curcumin (CUR) in physiological systems. The mechanism underlying the anticancer effect of THC is not completely understood. In the present study, we investigated the effects of THC on tumor growth and cellular signaling in cervical cancer xenografts in nude mice. Cervical cancer cells (CaSki) were subcutaneously injected in nude mice to establish tumors. One month after the injection, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. Relative tumor volume (RTV) was measured every 3-4 days. COX-2, EGFR, p-ERK1&2, p-AKT, and Ki-67 expressions were measured by immunohistochemistry whereas cell apoptosis was detected by TUNELS method. THC treatments at the doses of 100, 300, and 500 mg/kg statistically retarded the RTV by 70.40%, 76.41%, and 77.93%, respectively. The CaSki + vehicle group also showed significantly increased COX-2, EGFR, p ERK1&2, and p-AKT; however they were attenuated by all treatments with THC. Ki-67 overexpression and a decreasing of cell apoptosis were found in CaSki + vehicle group, but these findings were reversed after the THC treatments. PMID- 26881215 TI - Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model. AB - INTRODUCTION: Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD) and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. METHODS: Adult male Wistar rats were studied in an adjuvant arthritis (AA) model induced by the injection of Freund's complete adjuvant (FCA). Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1) and transforming growth factor-beta (TGF-beta1) protein expression levels. RESULTS: Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-beta1 protein expression was significantly increased on day 28 after FCA injection compared to control (P < 0.05). CONCLUSION: We established an AA rat model that exhibited the extra-articular complication of RA ILD. We identified Cav-1 and TGF-beta1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention. PMID- 26881216 TI - Characteristics of Salmonella spp. Isolated from Wild Birds Confiscated in Illegal Trade Markets, Rio de Janeiro, Brazil. AB - The prevalence of Salmonella spp. was investigated in 109 wild birds poached in the illegal wildlife trade in Rio de Janeiro; most of them are passerines from Thraupidae family and three from Psittacidae. One strain of Salmonella ser. Typhimurium and two strains of Salmonella ser. Panama were isolated from passerine species and all of them showed resistance to multiple antimicrobial drugs, like ampicillin, ceftriaxone, ceftiofur, tetracycline, gentamicin, nalidixic acid, ciprofloxacin, and enrofloxacin. PFGE showed 100% similarity among the Salmonella ser. Typhimurium strain isolated from a Temminck's seedeater (Sporophila falcirostris) and the strains isolated from a human outbreak, in southern Brazil. The two Salmonella ser. Panama strains isolated from two chestnut-capped blackbirds (Chrysomus ruficapillus) present in the same catch showed the same clonal origin and have never been associated with epizooties and human outbreaks. Potential for dissemination of resistant Salmonella through situations offered by captive management and the isolation of the same strain from wild birds and human sources may become a problem for the conservation of natural populations and to public health. PMID- 26881217 TI - Modification of the Sweetness and Stability of Sweet-Tasting Protein Monellin by Gene Mutation and Protein Engineering. AB - Natural sweet protein monellin has a high sweetness and low calorie, suggesting its potential in food applications. However, due to its low heat and acid resistance, the application of monellin is limited. In this study, we show that the thermostability of monellin can be improved with no sweetness decrease by means of sequence, structure analysis, and site-directed mutagenesis. We analyzed residues located in the alpha-helix as well as an ionizable residue C41. Of the mutants investigated, the effects of E23A and C41A mutants were most remarkable. The former displayed significantly improved thermal stability, while its sweetness was not changed. The mutated protein was stable after 30 min incubation at 85 degrees C. The latter showed increased sweetness and slight improvement of thermostability. Furthermore, we found that most mutants enhancing the thermostability of the protein were distributed at the two ends of alpha-helix. Molecular biophysics analysis revealed that the state of buried ionizable residues may account for the modulated properties of mutated proteins. Our results prove that the properties of sweet protein monellin can be modified by means of bioinformatics analysis, gene manipulation, and protein modification, highlighting the possibility of designing novel effective sweet proteins based on structure-function relationships. PMID- 26881218 TI - Prevalence and Predictors of Self-Medication with Antibiotics in Al Wazarat Health Center, Riyadh City, KSA. AB - BACKGROUND: Antibiotics are responsible for most dramatic improvement in medical therapy in history. These medications contributed significantly to the decreasing mortality and morbidity when prescribed based on evidence of microbial infection. OBJECTIVE: The aim of this study was to determine the prevalence and predictors of self-prescription with antibiotics in Al Wazarat Health Center, Riyadh City, Kingdom of Saudi Arabia. MATERIAL AND METHODS: Cross-sectional study was conducted in Al Wazarat Health Center between February 2014 and November 2014. Respondents were randomly selected using a multistage clustered random sampling technique. Data was entered into SPSS version 21 and analyzed. Descriptive statistics and multiple logistic regression models were applied. RESULTS: A total of 681 patients have participated in this study with a response rate of 92%. The prevalence of self-prescription with antibiotics in Al Wazarat Health Center was 78.7%. Amoxicillin was the most used self-prescribed antibiotic with prevalence of (22.3%). Friend advice on self-prescription of antibiotics use (p = 0.000) and pharmacy near to the participants (p = 0.002) were the most common predictors for self-prescription with antibiotics. CONCLUSION: The level of self-prescribing antibiotics is relatively high among participants. Health education on the appropriate use of antibiotics is highly recommended. The proper use of treatment guidelines for antibiotic therapy will significantly reduce self-prescription with antibiotics. PMID- 26881221 TI - Addressing Peritoneal Dialysis: In Vitro PD Models, In Vivo Rodent PD Model, Clinical Biobanks, and Underutilization of PD. PMID- 26881219 TI - New Therapeutic Concept of NAD Redox Balance for Cisplatin Nephrotoxicity. AB - Cisplatin is a widely used chemotherapeutic agent for the treatment of various tumors. In addition to its antitumor activity, cisplatin affects normal cells and may induce adverse effects such as ototoxicity, nephrotoxicity, and peripheral neuropathy. Various mechanisms such as DNA adduct formation, mitochondrial dysfunction, oxidative stress, and inflammatory responses are closely associated with cisplatin-induced nephrotoxicity; however, the precise mechanism remains unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as a key regulator of cellular energy metabolism and homeostasis. Recent studies have demonstrated associations between disturbance in intracellular NAD(+) levels and clinical progression of various diseases through the production of reactive oxygen species and inflammation. Furthermore, we demonstrated that reduction of the intracellular NAD(+)/NADH ratio is critically involved in cisplatin-induced kidney damage through inflammation and oxidative stress and that increase of the cellular NAD(+)/NADH ratio suppresses cisplatin-induced kidney damage by modulation of potential damage mediators such as oxidative stress and inflammatory responses. In this review, we describe the role of NAD(+) metabolism in cisplatin-induced nephrotoxicity and discuss a potential strategy for the prevention or treatment of cisplatin-induced adverse effects with a particular focus on NAD(+)-dependent cellular pathways. PMID- 26881220 TI - Cartilage Regeneration in Human with Adipose Tissue-Derived Stem Cells: Current Status in Clinical Implications. AB - Osteoarthritis (OA) is one of the most common debilitating disorders among the elderly population. At present, there is no definite cure for the underlying causes of OA. However, adipose tissue-derived stem cells (ADSCs) in the form of stromal vascular fraction (SVF) may offer an alternative at this time. ADSCs are one type of mesenchymal stem cells that have been utilized and have demonstrated an ability to regenerate cartilage. ADSCs have been shown to regenerate cartilage in a variety of animal models also. Non-culture-expanded ADSCs, in the form of SVF along with platelet rich plasma (PRP), have recently been used in humans to treat OA and other cartilage abnormalities. These ADSCs have demonstrated effectiveness without any serious side effects. However, due to regulatory issues, only ADSCs in the form of SVF are currently allowed for clinical uses in humans. Culture-expanded ADSCs, although more convenient, require clinical trials for a regulatory approval prior to uses in clinical settings. Here we present a systematic review of currently available clinical studies involving ADSCs in the form of SVF and in the culture-expanded form, with or without PRP, highlighting the clinical effectiveness and safety in treating OA. PMID- 26881222 TI - Encoding and Recognition Processing of Chinese Characters: A Functional Magnetic Resonance Imaging Study. AB - This study aimed to investigate the conceptual memory processes that underlie encoding and recognition processing of Chinese characters. Healthy participants (n = 14) performed a semantic-relatedness paradigm using categorically related logogram pairs from four different categories (fruit, animal, tool, and clothing). During intentional encoding, subjects were instructed to make semantic judgments and select category-correlated features to bind and memorize logogram pairs. During recognition, subjects were asked to recognize the memorized items. The MATLAB software and spatial clustering analysis were used for image data processing. Compared with baseline, encoding mainly activated BA13, with significant effects in BA6/8/9/46/45/47, BA24, BA7/39/40, BA37/20, and BA18/19; meanwhile, recognition mainly activated BA6/8/9/10/13/45/46/47, BA31, BA7/40, and BA18/19. Compared with recognition, encoding activated BA18/19/37/20/36 with a peak activation area in BA18. Compared with encoding, recognition significantly activated BA7, BA31/32, and BA10. In conclusion, distributed networks of discrete cortical regions with distinct roles are active during semantic processing of logograms. The ventral occipitotemporal and inferior frontal regions display increased levels of encoding-related activity. The dorsal medial brain regions, including the superior frontal gyrus and occipitoparietal regions, are associated with recognition-related activity. PMID- 26881225 TI - The Correlation of Age and Postoperative Visual Acuity for Age-Related Cataract. AB - PURPOSE: Clinically, what is the best time for age-related cataract (ARC) patients to receive surgeries and get the most benefits is important. We explored the relationship between age and presenting postoperative visual acuity (POVA) in patients from rural China. METHODS: Three Lifeline Express Hospital Eye-Train missions of Peking University People's Hospital were chosen. At the first day after surgery, 3452 ARC eyes with the presenting POVA >= 6/60 were enrolled. The relationship between age and POVA was analyzed statistically. RESULTS: In these three missions, there were more female patients than males; the ratio of females to males was 1.71. The average age of females was older than males. Overall, the percentages of patients with good visual outcomes (>=6/18) were significantly decreased with aging. Different regions had variations, but the trends were the same. There was weak linear correlation between age and POVA. The correlations of females were stronger than males in Yuncheng and Sanmenxia and weaker than males in Zhoukou. CONCLUSION: The good visual outcomes of presenting POVA were significantly decreased with aging and there were weak linear correlations between age and POVA in rural China. The linear correlation might be influenced by the difference of gender and region. PMID- 26881223 TI - MicroRNAs: Novel Crossroads between Myeloma Cells and the Bone Marrow Microenvironment. AB - Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulate in the bone marrow, where a complex microenvironment made by different cell types supports proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at posttranscriptional level. Emerging evidence indicates that miRNAs are aberrantly expressed or functionally deregulated in MM cells as the result of multiple genetic or epigenetic mechanisms and that also the tumor microenvironment regulates MM cell functions by miRNAs. Consistently, modulation of miRNA levels in MM cells has been demonstrated to impair their functional interaction with the bone marrow microenvironment and to produce significant antitumor activity even able to overcome the protective bone marrow milieu. This review will describe the most recent findings on miRNA function in the context of MM bone marrow microenvironment, focusing on the therapeutic potential of miRNA based approaches. PMID- 26881226 TI - Intraoral Digital Impressions for Virtual Occlusal Records: Section Quantity and Dimensions. AB - The purpose of this study was to locate the 3D spatial position mandibular cast and determine its occlusal contacts in a novel way by using an intraoral scanner as part of the virtual occlusal record procedure. This study also analyzes the requirements in quantity and dimensions of the intraoral virtual occlusal record. The results showed that the best section combination consists of 2 lateral and frontal sections, the width of this section being that of 2 teeth (24 mm * 15 mm). This study concluded that this procedure was accurate enough to locate the mandibular cast on a virtual articulator. However, at least 2 sections of the virtual occlusal records were necessary, and the best results were obtained when the distance between these sections was maximum. PMID- 26881224 TI - Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain. AB - Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID- 26881227 TI - Sandwich Immunoassays of Multicomponent Subtrace Pathogenic DNA Based on Magnetic Fluorescent Encoded Nanoparticles. AB - A novel magnetic fluorescent encoded nanoimmunoassay system for multicomponent detection and separation of the subtrace pathogenic DNA (hepatitis B virus surface gene, HBV; hepatitis A virus poly the protein gene, HAV) was established based on new type of magnetic fluorescent encoded nanoparticles and sandwich immunoassay principle. This method combines multifunctional nanoparticles, immunoassay technique, fluorescence labeling, and magnetic separation of multicomponent technology. It has many advantages such as high sensitivity, low detection limit, easy operation, and great potential for development. The results of this work show that, based on nanoimmunoassay system, it could quantitatively detect the multicomponent trace pathogenic HAV and HBV DNA, as well as detection limit up to 0.1 pM and 0.12 pM. Furthermore, with the improvement of the performances of magnetic fluorescent encoded nanoparticles, the sensitivity will be further improved. In this experiment, a new nanoimmunoassay system based on magnetic fluorescent encoded nanoparticles was established, which will provide a new way for the immunoassay and separation of multicomponent biomolecules. PMID- 26881232 TI - Application of Innovative Technologies for Improved Food Quality and Safety. PMID- 26881228 TI - One-Year Outcome of Geriatric Hip-Fracture Patients following Prolonged ICU Treatment. AB - PURPOSE: Incidence of geriatric fractures is increasing. Knowledge of outcome data for hip-fracture patients undergoing intensive-care unit (ICU) treatment, including invasive ventilatory management (IVM) and hemodiafiltration (CVVHDF), is sparse. METHODS: Single-center prospective observational study including 402 geriatric hip-fracture patients. Age, gender, the American Society of Anesthesiologists (ASA) classification, and the Barthel index (BI) were documented. Underlying reasons for prolonged ICU stay were registered, as well as assessed procedures like IVM and CVVHDF. Outcome parameters were in-hospital, 6 month, and 1-year mortality and need for nursing care. RESULTS: 15% were treated > 3 days and 68% < 3 days in ICU. Both cohorts had similar ASA, BI, and age. In hospital, 6-month, and 12-month mortality of ICU > 3d cohort were significantly increased (p = 0.001). Most frequent indications were cardiocirculatory pathology followed by respiratory failure, renal impairment, and infection. 18% of patients needed CVVHDF and 41% IVM. In these cohorts, 6-month mortality ranged > 80% and 12-month mortality > 90%. 100% needed nursing care after 6 and 12 months. Conclusions. ICU treatment > 3 days showed considerable difference in mortality and nursing care needed after 6 and 12 months. Particularly, patients requiring CVVHDF or IVM had disastrous long-term results. Our study may add one further element in complex decision making serving this vulnerable patient cohort. PMID- 26881230 TI - Improvement in the Detection of Cystic Metastatic Papillary Thyroid Carcinoma by Measurement of Thyroglobulin in Aspirated Fluid. AB - Cystic change in metastatic lymph nodes of papillary thyroid carcinoma (PTC) is a diagnostic challenge for fine needle aspiration (FNA) because of the scant cellularity. The aim of this study was to evaluate the measurement of thyroglobulin in fine needle aspirate (Tg-FNA) for detecting metastatic PTC in patients with cystic neck lesions and to validate the optimal cutoff value of Tg FNA. A total of 75 FNA specimens of cystic lesions were identified, including 40 of metastatic PTC. Predetermined threshold levels of 0.04 (minimum detection level), 0.9, 10.0, and 77.0 ng/mL (maximum normal serum-Tg level) were used to evaluate the diagnostic accuracy of Tg-FNA for metastatic PTC detection. The areas under the receiver operating characteristic curve for diagnosing metastatic PTC of Tg-FNA values of 0.04, 0.9, 10.0, and 77.0 ng/mL were 0.5 (95% confidence interval [CI], 0.382-0.618), 0.645 (95% CI, 0.526-0.752), 0.945 (95% CI, 0.866 0.984), and 0.973 (95% CI, 0.907-0.996), respectively. With a cutoff value of 77.0 ng/mL, the combination of Tg-FNA and FNA cytology showed superior diagnostic power (97.5% sensitivity and 100% specificity) compared to FNA cytology alone (80% sensitivity and 100% specificity). We recommend a Tg-FNA cutoff of 77.0 ng/mL, the maximum normal serum-Tg level, for cystic neck lesions. PMID- 26881229 TI - Polymorphisms in DNA Repair Gene XRCC3 and Susceptibility to Breast Cancer in Saudi Females. AB - We investigated three common polymorphisms (SNPs) in the XRCC3 gene (rs861539, rs1799794, and rs1799796) in 143 Saudi females suffering from breast cancer (median age = 51.4 years) and 145 age matched normal healthy controls. DNA was extracted from whole blood and genotyping was conducted using PCR-RFLP. rs1799794 showed significant association, where AA and AA+AG occurred at a significantly higher frequency in the cancer patients compared to the control group (OR: 28.1; 95% CI: 3.76-21.12; chi (2): 22.82; p < 0.0001). The G allele was protective and presented with a dominant model. The genotype and allele frequencies of rs861539 C>T and rs1799796 A>G did not show a significant difference when the results in the patients and controls were compared. However, the frequency of rs1799796 differed significantly in patients with different age of diagnosis, tumor grade, and ER and HER2 status. The wild type A allele occurred at a higher frequency in the ER- and HER2- group. Our results among Saudis suggest that some variations in XRCC3 may contribute to breast cancer susceptibility. In conclusion, the results obtained during this study suggest that rs1799794 in XRCC3 shows strong association with breast cancer development in Saudi females. PMID- 26881231 TI - Disease Combinations Associated with Physical Activity Identified: The SMILE Cohort Study. AB - In the search of predictors of inadequate physical activity, an investigation was conducted into the association between multimorbidity and physical activity (PA). So far the sum of diseases used as a measure of multimorbidity reveals an inverse association. How specific combinations of chronic diseases are associated with PA remains unclear. The objective of this study is to identify clusters of multimorbidity that are associated with PA. Cross-sectional data of 3,386 patients from the 2003 wave of the Dutch cohort study SMILE were used. Ward's agglomerative hierarchical clustering was executed to establish multimorbidity clusters. Chi-square statistics were used to assess the association between clusters of chronic diseases and PA, measured in compliance with the Dutch PA guideline. The highest rate of PA guideline compliance was found in patients the majority of whom suffer from liver disease, back problems, rheumatoid arthritis, osteoarthritis, and inflammatory joint disease (62.4%). The lowest rate of PA guideline compliance was reported in patients with heart disease, respiratory disease, and diabetes mellitus (55.8%). Within the group of people with multimorbidity, those suffering from heart disease, respiratory disease, and/or diabetes mellitus may constitute a priority population as PA has proven to be effective in the prevention and cure of all three disorders. PMID- 26881233 TI - South Vietnamese Rural Mothers' Knowledge, Attitude, and Practice in Child Health Care. AB - A study of 600 rural under-five mothers' knowledge, attitude, and practice (KAP) in child care was performed in 4 southern provinces of Vietnam. The mothers were randomly selected and interviewed about sociodemographic factors, health seeking behaviour, and practice of home care of children and neonates. 93.2% of the mothers were literate and well-educated, which has been shown to be important for child health care. 98.5% were married suggesting a stable family, which is also of importance for child health. Only 17.3% had more than 2 children in their family. The mother was the main caretaker in 77.7% of the families. Only 1% would use quacks as their first health contact, but 25.2% would use a private clinic, which therefore eases the burden on the government system. Nearly 69% had given birth in a hospital, 27% in a commune health station, and only 2.7% at home without qualified assistance. 89% were giving exclusive breast feeding at 6 months, much more frequent than in the cities. The majority of the mothers could follow IMCI guideline for home care, although 25.2% did not deal correctly with cough and 38.7% did not deal correctly with diarrhoea. Standard information about Integrated Management of Childhood Illnesses (IMCI) based home care is still needed. PMID- 26881235 TI - Outcomes of Various Interventions for First-Time Perianal Abscesses in Children. AB - INTRODUCTION: In children treated surgically for first-time perianal abscesses, discovery and excision of concomitant fistulas may also be warranted. AIM: To evaluate children of varying age after incision and drainage of first-time perianal abscesses, examining recurrences rates with and without search for a fistula. METHOD: A retrospective review was conducted, analyzing children (ages 0 15 years) treated for first-time perianal abscesses at a tertiary pediatric surgical center, with a minimum follow-up of 6 months. RESULTS: A total of 104 patients subjected to 112 treatments for first-time perianal abscesses were eligible. Surgical procedures constituted 84 (75%) of treatments, searching for fistulas in 49 (58%). In 34 (69%), fistulas were confirmed and treated. In the surgically treated subset, the recurrence rate was higher if no attempt was made to exclude a fistula (46%), as opposed to confirmed absence of a fistula (27%) or concurrent fistulotomy (9%; p = 0.02). Younger patients showed a higher recurrence rate (12/26; 46%), compared with older counterparts (11/58; 19%) (p = 0.002). CONCLUSION: In children surgically treated for first-time perianal abscess, recurrence rates appear to be lowered by locating and treating coexisting fistulas. PMID- 26881237 TI - Vascular Endothelial Growth Factor Gene Polymorphism (rs2010963) and Its Receptor, Kinase Insert Domain-Containing Receptor Gene Polymorphism (rs2071559), and Markers of Carotid Atherosclerosis in Patients with Type 2 Diabetes Mellitus. AB - Background. The current study was designed to reveal possible associations between the polymorphisms of the vascular endothelial growth factor (VEGF) gene (rs2010963) and its receptor, kinase insert domain-containing receptor (KDR) gene polymorphism (rs2071559), and markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 595 T2DM subjects and 200 control subjects were enrolled. The carotid intima-media thickness (CIMT) and plaque characteristics (presence and structure) were assessed ultrasonographically. Biochemical analyses were performed using standard biochemical methods. Genotyping of VEGF/KDR polymorphisms (rs2010963, rs2071559) was performed using KASPar assays. Results. Genotype distributions and allele frequencies of the VEGF/KDR polymorphisms (rs2010963, rs2071559) were not statistically significantly different between diabetic patients and controls. In our study, we demonstrated an association between the rs2071559 of KDR and either CIMT or the sum of plaque thickness in subjects with T2DM. We did not, however, demonstrate any association between the tested polymorphism of VEGF (rs2010963) and either CIMT, the sum of plaque thickness, the number of involved segments, hsCRP, the presence of carotid plaques, or the presence of unstable carotid plaques. Conclusions. In the present study, we demonstrated minor effect of the rs2071559 of KDR on markers of carotid atherosclerosis in subjects with T2DM. PMID- 26881236 TI - Incretin-Based Therapy for Prevention of Diabetic Vascular Complications. AB - Diabetic vascular complications are the most common cause of mortality and morbidity worldwide, with numbers of affected individuals steadily increasing. Diabetic vascular complications can be divided into two categories: macrovascular andmicrovascular complications. Macrovascular complications include coronary artery diseaseand cerebrovascular disease, while microvascular complications include retinopathy and chronic kidney disease. These complications result from metabolic abnormalities, including hyperglycemia, elevated levels of free fatty acids, and insulin resistance. Multiple mechanisms have been proposed to mediate the adverse effects of these metabolic disorders on vascular tissues, including stimulation of protein kinase C signaling and activation of the polyol pathway by oxidative stress and inflammation. Additionally, the loss of tissue-specific insulin signaling induced by hyperglycemia and toxic metabolites can induce cellular dysfunction and both macro- and microvascular complications characteristic of diabetes. Despite these insights, few therapeutic methods are available for the management of diabetic complications. Recently, incretin-based therapeutic agents, such as glucagon-like peptide-1 and dipeptidyl peptidase-4 inhibitors, have been reported to elicit vasotropic actions, suggesting a potential for effecting an actual reduction in diabetic vascular complications. The present review will summarize the relationship between multiple adverse biological mechanisms in diabetes and putative incretin-based therapeutic interventions intended to prevent diabetic vascular complications. PMID- 26881234 TI - The Impact of Sperm Metabolism during In Vitro Storage: The Stallion as a Model. AB - In vitro sperm storage is a necessary part of many artificial insemination or in vitro fertilization regimes for many species, including the human and the horse. In many situations spermatozoa are chilled to temperatures between 4 and 10 degrees C for the purpose of restricting the metabolic rate during storage, in turn, reducing the depletion of ATP and the production of detrimental by-products such as reactive oxygen species (ROS). Another result of lowering the temperature is that spermatozoa may be "cold shocked" due to lipid membrane phase separation, resulting in reduced fertility. To overcome this, a method of sperm storage must be developed that will preclude the need to chill spermatozoa. If a thermally induced restriction-of-metabolic-rate strategy is not employed, ATP production must be supported while ameliorating the deleterious effects of ROS. To achieve this end, an understanding of the nature of energy production by the spermatozoa of the species of interest is essential. Human spermatozoa depend predominantly on glycolytic ATP production, producing significantly less ROS than oxidative phosphorylation, with the more efficient pathway predominantly employed by stallion spermatozoa. This review provides an overview of the implications of sperm metabolism for in vitro sperm storage, with a focus on ambient temperature storage in the stallion. PMID- 26881238 TI - Free Fatty Acids Activate Renin-Angiotensin System in 3T3-L1 Adipocytes through Nuclear Factor-kappa B Pathway. AB - The activity of a local renin-angiotensin system (RAS) in the adipose tissue is closely associated with obesity-related diseases. However, the mechanism of RAS activation in adipose tissue is still unknown. In the current study, we found that palmitic acid (PA), one kind of free fatty acid, induced the activity of RAS in 3T3-L1 adipocytes. In the presence of fetuin A (Fet A), PA upregulated the expression of angiotensinogen (AGT) and angiotensin type 1 receptor (AT1R) and stimulated the secretion of angiotensin II (ANG II) in 3T3-L1 adipocytes. Moreover, the activation of RAS in 3T3-L1 adipocytes was blocked when we blocked Toll-like receptor 4 (TLR4) signaling pathway using TAK242 or NF-kappaB signaling pathway using BAY117082. Together, our results have identified critical molecular mechanisms linking PA/TLR4/NF-kappaB signaling pathway to the activity of the local renin-angiotensin system in adipose tissue. PMID- 26881240 TI - New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy. AB - Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID- 26881242 TI - Community-Based Diabetes Screening and Risk Assessment in Rural West Virginia. AB - This project utilized a cross-sectional study design to assess diabetes risk among 540 individuals from 12 counties using trained extension agents and community organizations in West Virginia. Individuals were screened for diabetes using (1) the validated 7-item diabetes risk assessment survey and (2) hemoglobin A1c tests. Demographic and lifestyle behaviors were also collected. The average age, body mass index, and A1c were 51.2 +/- 16.4, 31.1 +/- 7.5, and 5.8 +/- 0.74, respectively. The majority were females, Non-Hispanic Whites with no prior diagnosis of diabetes. Screenings showed that 61.8% of participants were at high risk for diabetes. Family history of diabetes (siblings or parents), overweight or obese status, sedentary lifestyle, and older age were commonly prevalent risk factors. Higher risk scores computed from the 7-item questions correlated positively with higher A1c (r = 0.221, P < 0.001). In multivariate logistic regression analyses, higher diabetes risk was predicted by obesity, older age, family history of hypertension, and gestational diabetes. Females were 4 times at higher risk than males. The findings indicated that community-based screenings were an effective way to assess diabetes risk in rural West Virginia. Linking diabetes screenings with referrals to lifestyle programs for high risk individuals can help reduce the burden of diabetes in the state. PMID- 26881241 TI - Tyrosine Is Associated with Insulin Resistance in Longitudinal Metabolomic Profiling of Obese Children. AB - In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p < 0.05) at baseline and end and with change during the intervention (p < 0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p < 0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov Identifier NCT00435734. PMID- 26881243 TI - The Motivating Function of Healthcare Professional in eHealth and mHealth Interventions for Type 2 Diabetes Patients and the Mediating Role of Patient Engagement. AB - eHealth and mHealth interventions for type 2 diabetes are emerging as useful strategies to accomplish the goal of a high functioning integrated care system. However, mHealth and eHealth interventions in order to be successful need the clear endorsement from the healthcare professionals. This cross-sectional study included a sample of 93 Italian-speaking type 2 diabetes patients and demonstrated the role of the perceived ability of healthcare professionals to motivate patients' initiative in improving the level of their engagement and activation in type 2 diabetes self-management. The level of type 2 diabetes patients' activation resulted also in being a direct precursor of their attitude to the use of mHealth and eHealth. Furthermore, patient engagement has been demonstrated to be a mediator of the relationship between the perceived ability of healthcare professionals in motivating type 2 diabetes patients and patients' activation. Finally, type 2 diabetes patients adherence did not result in being a direct consequence of the frequency of mHealth and eHealth use. Patient adherence appeared to be directly influenced by the level of perceived healthcare professionals ability of motivating patients' autonomy. These results offer important insights into the psychosocial and organizational elements that impact on type 2 diabetes patients' activation in self-management and on their willingness to use mHealth and eHealth devices. PMID- 26881239 TI - Vitamin B6 Prevents Endothelial Dysfunction, Insulin Resistance, and Hepatic Lipid Accumulation in Apoe (-/-) Mice Fed with High-Fat Diet. AB - Backgrounds. VitB6 deficiency has been associated with a number of adverse health effects. However, the effects of VitB6 in metabolic syndrome are poorly understood. Methods. VitB6 (50 mg/kg/day) was given to Apoe (-/-) mice with hkdigh-fat diet (HFD) for 8 weeks. Endothelial dysfunction, insulin resistance, and hepatic lipid contents were determined. Results. VitB6 administration remarkably increased acetylcholine-induced endothelium-dependent relaxation and decreased random blood glucose level in Apoe (-/-) mice fed with HFD. In addition, VitB6 improved the tolerance of glucose and insulin, normalized the histopathology of liver, and reduced hepatic lipid accumulation but did not affect the liver functions. Clinical and biochemical analysis indicated that the levels of VitB6 were decreased in patients with fatty liver. Conclusions. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in Apoe (-/-) mice fed with HFD. Supplementation of VitB6 should be considered to prevent metabolic syndrome. PMID- 26881244 TI - Conserved Metabolic Changes in Nondiabetic and Type 2 Diabetic Bariatric Surgery Patients: Global Metabolomic Pilot Study. AB - The goal of this study was to provide insight into the mechanism by which bariatric surgical procedures led to weight loss and improvement or resolution of diabetes. Global biochemical profiling was used to evaluate changes occurring in nondiabetic and type 2 diabetic (T2D) patients experiencing either less extreme sleeve gastrectomy or a full gastric bypass. We were able to identify changes in metabolism that were affected by standard preoperation liquid weight loss diet as well as by bariatric surgery itself. Preoperation weight-loss diet was associated with a strong lipid metabolism signature largely related to the consumption of adipose reserves for energy production. Glucose usage shift away from glycolytic pyruvate production toward pentose phosphate pathway, via glucose-6-phosphate, appeared to be shared across all patients regardless of T2D status or bariatric surgery procedure. Our results suggested that bariatric surgery might promote antioxidant defense and insulin sensitivity through both increased heme synthesis and HO activity or expression. Changes in histidine and its metabolites following surgery might be an indication of altered gut microbiome ecology or liver function. This initial study provided broad understanding of how metabolism changed globally in morbidly obese nondiabetic and T2D patients following weight loss surgery. PMID- 26881245 TI - Diabetes Mellitus in Outpatients in Debre Berhan Referral Hospital, Ethiopia. AB - INTRODUCTION: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Most people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years. OBJECTIVE: To assess the prevalence and associated factors of diabetes mellitus among outpatients of Debre Berhan Referral Hospital. METHODS AND MATERIALS: A cross-sectional study was conducted from April to June 2015 among 385 patients. Random quota sampling technique was used to get individual patients and risk factors assessment. Patients diabetes status was ascertained by World Health Organization Diabetes Mellitus Diagnostic Criteria. The collected data were entered, cleaned, and analyzed and Chi-square test was applied to test any association between dependent and independent variable. Result. Out of the total 385 study patients, 368 have participated in the study yielding a response rate of 95.3%. Concerning clinical presentation of diabetes mellitus, 13.3% of patients reported thirst, 14.4% of patients declared polyurea, and 14.9% of patients ascertained unexplained weight loss. The statistically significant associated factors of diabetes mellitus were hypertensive history, obesity, the number of parities, and smoking history. CONCLUSION: The prevalence of diabetes mellitus among outpatients in Debre Berhan Referral Hospital was 0.34% and several clinical and behavioral factors contribute to the occurrence of diabetes mellitus which impose initiation of preventive, promotive, and curative strategies. PMID- 26881246 TI - Diabetic Retinopathy: Animal Models, Therapies, and Perspectives. AB - Diabetic retinopathy (DR) is one of the major complications of diabetes. Although great efforts have been made to uncover the mechanisms underlying the pathology of DR, the exact causes of DR remain largely unknown. Because of multifactor involvement in DR etiology, currently no effective therapeutic treatments for DR are available. In this paper, we review the pathology of DR, commonly used animal models, and novel therapeutic approaches. Perspectives and future directions for DR treatment are discussed. PMID- 26881247 TI - Metabolic Health Has Greater Impact on Diabetes than Simple Overweight/Obesity in Mexican Americans. AB - PURPOSE: To compare the risk for diabetes in each of 4 categories of metabolic health and BMI. METHODS: Participants were drawn from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border. Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically healthy overweight/obese, metabolically unhealthy normal weight, and metabolically unhealthy overweight/obese. Metabolic health was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m(2). Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication. RESULTS: The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79), 3.78 (1.57, 9.09) in the metabolically unhealthy normal weight phenotype, and 5.39 (3.16, 9.20) in metabolically unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal weight phenotype. CONCLUSIONS: Metabolic health had a greater effect on the increased risk for diabetes than overweight/obesity. Greater focus on metabolic health might be a more effective target for prevention and control of diabetes than emphasis on weight loss alone. PMID- 26881248 TI - Gmelina arborea Roxb. (Family: Verbenaceae) Extract Upregulates the beta-Cell Regeneration in STZ Induced Diabetic Rats. AB - Gmelina arborea Roxb. (common name: Et-demata, Family: Verbenaceae) has been used traditionally in Sri Lanka as a remedy against diabetes mellitus. The objective of the present study was to evaluate antidiabetic mechanisms of the aqueous bark extract of G. arborea in streptozotocin induced (STZ) diabetic male Wistar rats. Aqueous bark extract of G. arborea (1.00 g/kg) and glibenclamide as the standard drug (0.50 mg/kg) were administered orally using a gavage to STZ diabetic rats (65 mg/kg, ip) for 30 days. The antidiabetic mechanisms of aqueous extract of G. arborea (1.00 g/kg) were determined at the end of the experiment. The fasting blood glucose concentration was significantly lowered and the serum insulin and C peptide concentrations were increased by 57% and 39% in plant extract treated rats on day 30, respectively (p < 0.05). The histopathology and immunohistochemistry results of the plant extract treated group showed a regenerative effect on beta-cells of the pancreas in diabetic rats. In addition, serum lipid parameters were improved in G. arborea extract treated diabetic rats. The results revealed that the aqueous stem bark extract of G. arborea (1.00 g/kg) showed beneficial effects against diabetes mellitus through upregulating the beta cell regeneration and biosynthesis of insulin in diabetic rats. PMID- 26881250 TI - Diabetic Nephropathy: Proteinuria, Inflammation, and Fibrosis. PMID- 26881249 TI - Transgenerational Glucose Intolerance of Tumor Necrosis Factor with Epigenetic Alteration in Rat Perirenal Adipose Tissue Induced by Intrauterine Hyperglycemia. AB - Changes in DNA methylation may play a role in the genetic mechanism underlying glucose intolerance in the offspring of mothers with diabetes. Here, we established a rat model of moderate intrauterine hyperglycemia induced by streptozotocin to detect glucose and lipid metabolism of first-generation (F1) and second-generation (F2) offspring. Moderate intrauterine hyperglycemia induced high body weight in F1 and F2 offspring of diabetic mothers. F1 offspring had impaired glucose tolerance and abnormal insulin level. Additionally, F1 and F2 offspring that were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets. The tumor necrosis factor (Tnf) gene was upregulated in perirenal adipose tissue from F1 offspring and relatively increased in F2 offspring. Both F1 and F2 offspring showed similar hypomethylation level at the 1952 site of Tnf. We confirmed that DNA methylation occurs in offspring exposed to intrauterine hyperglycemia and that the DNA methylation is intergenerational and inherited. PMID- 26881251 TI - Effect of Ranirestat on Sensory and Motor Nerve Function in Japanese Patients with Diabetic Polyneuropathy: A Randomized Double-Blind Placebo-Controlled Study. AB - We conducted a 26-week oral-administration study of ranirestat (an aldose reductase inhibitor) at a once-daily dose of 20 mg to evaluate its efficacy and safety in Japanese patients with diabetic polyneuropathy (DPN). The primary endpoint was summed change in sensory nerve conduction velocity (NCV) for the bilateral sural and proximal median sensory nerves. The sensory NCV was significantly (P = 0.006) improved by ranirestat. On clinical symptoms evaluated with the use of modified Toronto Clinical Neuropathy Score (mTCNS), obvious efficacy was not found in total score. However, improvement in the sensory test domain of the mTCNS was significant (P = 0.037) in a subgroup of patients diagnosed with neuropathy according to the TCNS severity classification. No clinically significant effects on safety parameters including hepatic and renal functions were observed. Our results indicate that ranirestat is effective on DPN (Japic CTI-121994). PMID- 26881252 TI - The Stricter the Better? The Relationship between Targeted HbA1c Values and Metabolic Control of Pediatric Type 1 Diabetes Mellitus. AB - INTRODUCTION: It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. MATERIALS AND METHODS: We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. RESULTS: We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%-8.70%) and was lower in "6.5%" than in "7.5%" as targeted HbA1c level (8.20% (7.85%-8.57%) versus 8.40% (8.20%-8.80%); p = 0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%-1.70%) and was higher in "6.5%" than in "7.5%" (1.70% (1.30%-2.07%) versus 0.90% (0.70%-1.30%), resp.; p < 0.001). CONCLUSIONS: Our study indicates that the 7.5% threshold results in HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the "6.5%" group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further. PMID- 26881253 TI - Fyn Mediates High Glucose-Induced Actin Cytoskeleton Reorganization of Podocytes via Promoting ROCK Activation In Vitro. AB - Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation. PMID- 26881254 TI - Decrease in (Major) Amputations in Diabetics: A Secondary Data Analysis by AOK Rheinland/Hamburg. AB - AIM: In two German regions with 11.1 million inhabitants, 6 networks for specialized treatment of DFS were implemented until 2008. Data provided for accounting purposes was analysed in order to determine changes in the rate of diabetics requiring amputations in the years before and after the implementation. METHOD: Data covering 2.9 million people insured by the largest insurance company between 2007 and 2013 was analysed by the use of log-linear Poisson regression adjusted for age, gender and region. RESULTS: The rate of diabetics needing major amputations fell significantly by 9.5% per year (p < 0.0001) from 217 to 126 of 100,000 patients per year. The rate of diabetics needing amputations of any kind fell from 504 to 419 of 100,000 patients per year (p = 0.0038). DISCUSSION: The networks integrate health care providers in an organised system of shared care. They educate members of the medical community and the general public. At the same time, a more general disease management program for people with diabetes was implemented, which may also have contributed to this decrease. At the end of the observation period, the rate of diabetics requiring amputations was still high. For this reason, further expansion of organised specialized care is urgently needed. PMID- 26881255 TI - The Expression of miR-192 and Its Significance in Diabetic Nephropathy Patients with Different Urine Albumin Creatinine Ratio. AB - OBJECTIVE: To investigate the expression of miR-192 and its significance in diabetic nephropathy (DN) patients. METHODS: 464 patients with type 2 diabetes mellitus (T2DM) were divided into normal albuminuria group (NA, n = 157), microalbuminuria group (MA, n = 159), and large amount of albuminuria group (LA, n = 148). 127 healthy persons were selected as the control group (NC, n = 127). The serum miR-192 levels were detected by Real-Time PCR and transforming growth factor-beta1 (TGF-beta1) and fibronectin (FN) were detected by enzyme-linked immunosorbent assay. The relationships among these parameters were analyzed by Pearson correlation analysis and multiple linear regression analysis. RESULTS: The miR-192 in the LA group was significantly lower than other groups, which was lower in the MA group than in the NA group (P < 0.01). The TGF-beta1 and FN in the LA group were significantly higher than other groups, which were higher in the MA group than in the NA group (P < 0.01). The expression of miR-192 was negatively correlated with TGF-beta1, FN, and Ln (UACR) and miR-192, TGF-beta1, and FN were independent relevant factors affecting Ln (UACR) in T2DM (P < 0.01). CONCLUSIONS: These findings indicate that the levels of miR-192 were lower accompanied by the decrease of urine albumin creatinine ratio (UACR) and the association between miR-192 and nephritic fibrosis in DN. PMID- 26881257 TI - Hypoxia Alters the Expression of Dipeptidyl Peptidase 4 and Induces Developmental Remodeling of Human Preadipocytes. AB - Dipeptidyl peptidase 4 (DPP4), a transmembrane protein, has been identified in human adipose tissue and is considered to be associated with obesity-related type 2 diabetes. Since adipose tissue is relatively hypoxic in obese participants, we investigated the expression of DPP4 in human preadipocytes (hPA) and adipocytes in hypoxia, during differentiation and upon insulin stimulation. The results show that DPP4 is abundantly expressed in hPA but very sparsely in adipocytes. During differentiation in vitro, the expression of DPP4 in hPA is reduced on the addition of differentiation medium, indicating that this protein can be hPA marker. Long term hypoxia altered the expression of DPP4 in hPA. In in vitro hypoxic conditions the protease activity of shed DPP4 is reduced; however, in the presence of insulin, the increase in DPP4 expression is potentiated by hypoxia. PMID- 26881256 TI - High Glucose and Lipopolysaccharide Prime NLRP3 Inflammasome via ROS/TXNIP Pathway in Mesangial Cells. AB - While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1beta, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1beta was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL 1beta were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1beta inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy. PMID- 26881258 TI - Noninsulin Antidiabetic Drugs for Patients with Type 2 Diabetes Mellitus: Are We Respecting Their Contraindications? AB - AIM: To assess prescribing practices of noninsulin antidiabetic drugs (NIADs) in T2DM with several major contraindications according to prescribing information or clinical guidelines: renal failure, heart failure, liver dysfunction, or history of bladder cancer. METHODS: Cross-sectional, descriptive, multicenter study. Electronic medical records were retrieved from all T2DM subjects who attended primary care centers pertaining to the Catalan Health Institute in Catalonia in 2013 and were pharmacologically treated with any NIAD alone or in combination. RESULTS: Records were retrieved from a total of 255,499 pharmacologically treated patients. 78% of patients with some degree of renal impairment (glomerular filtration rate (GFR) < 60 mL/min) were treated with metformin and 31.2% with sulfonylureas. Even in the event of severe renal failure (GFR < 30 mL/min), 35.3% and 22.5% of patients were on metformin or sulfonylureas, respectively. Moreover, metformin was prescribed to more than 60% of patients with moderate or severe heart failure. CONCLUSION: Some NIADs, and in particular metformin, were frequently used in patients at high risk of complications when they were contraindicated. There is a need to increase awareness of potential inappropriate prescribing and to monitor the quality of prescribing patterns in order to help physicians and policymakers to yield better clinical outcomes in T2DM. PMID- 26881259 TI - Characteristics of Type 2 Diabetes with Ketosis in Baoshan, Yunnan of China. AB - OBJECTIVES: The study provided data to demonstrate the characteristics of type 2 diabetes (T2D) with ketosis in rural parts of south-west border of China in order to help health professionals with optimizing diabetic care. METHODS: All hospitalized adult diabetic patients consecutively between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan province of China, were evaluated. T2D with ketosis, ordinary T2D (without ketosis), and type 1 diabetes (T1D) patients were analyzed according to the clinical and biochemical parameters and chronic complications in these subjects. RESULTS: The prevalence of T2D with ketosis was 12% in the whole study subjects. Overweight and obese patients were predominant (49.1%) in T2D patients with ketosis. The mean HbA1c (13.3 +/- 3.1%, P = 0.01), fasting plasma glucose (16.9 +/- 6 mmol/L, P < 0.0001), and plasma triglyceride (4.0 +/- 4.0 mmol/L, P < 0.0001) in T2D patients with ketosis were significantly higher than ordinary T2D patients without ketosis. Infections were the most common inducements in T2D patients with ketosis. Chronic complications including peripheral neuropathy (34.9%), retinopathy (12.7%), diabetic foot (18.1%), and persistent microalbuminuria (11.7%) were common in T2D patients with ketosis. CONCLUSIONS: . This study indicated the poor glycemic control in diabetic patients in rural areas of south-west part of China. More efforts were urgently required to popularize public health education and improve medical quality in diabetic treatment in these regions. PMID- 26881260 TI - Puerarin Improves Diabetic Aorta Injury by Inhibiting NADPH Oxidase-Derived Oxidative Stress in STZ-Induced Diabetic Rats. AB - OBJECTIVE: Puerarin is a natural flavonoid isolated from the TCM lobed kudzuvine root. This study investigated the effect and mechanisms of puerarin on diabetic aorta in rats. METHODS: Streptozotocin- (STZ-) induced diabetic rats were administered with puerarin for 3 weeks. Levels of serum insulin (INS), PGE2, endothelin (ET), glycated hemoglobin (GHb), H2O2, and nitric oxide (NO) in rats were measured by ELISA and colorimetric assay kits. The aortas were stained with H&E. Moreover, the mRNA expression of ICAM-1, LOX-1, NADPH oxidase 2 (NOX2), and NOX4 and the protein expression of ICAM-1, LOX-1, NF-kappaB p65, E-selectin, NOX2, and NOX4 in aorta tissues were measured by real-time PCR and Western blot, respectively. The localization of ICAM-1, NF-kappaB p65, NOX2, and NOX4 in the aorta tissues was also determined through immunohistochemistry. RESULTS: Puerarin treatment exerted no effect on fasting blood glucose levels but significantly reduced the serum levels of INS, GHb, PGE2, ET, H2O2, and NO. In addition, puerarin improved the pathological alterations and inhibited the expression of ICAM-1, LOX-1, NOX2, and NOX4 at both mRNA and protein levels. Puerarin also significantly reduced the number of cells showing positive staining for ICAM-1, NOX2, NOX4, and NF-kappaB p65. CONCLUSION: Puerarin demonstrated protective effect on the STZ-induced diabetic rat aorta. The protective mechanisms may include regulation of NF-kappaB and inhibition of NOX2 and NOX4 followed by inhibition of cell adhesion molecule expression. PMID- 26881261 TI - Corrigendum to "Diabetes Remission after Nonsurgical Intensive Lifestyle Intervention in Obese Patients with Type 2 Diabetes". PMID- 26881262 TI - Knowledge and Lifestyle-Associated Prevalence of Obesity among Newly Diagnosed Type II Diabetes Mellitus Patients Attending Diabetic Clinic at Komfo Anokye Teaching Hospital, Kumasi, Ghana: A Hospital-Based Cross-Sectional Study. AB - This study aimed to determine the knowledge and prevalence of obesity among Ghanaian newly diagnosed type 2 diabetics. This cross-sectional study was conducted among diagnosed type 2 diabetics. Structured questionnaire was used to obtain data. Anthropometric measurements and fasting blood sugar levels were also assessed. Participants had adequate knowledge about the general concept of obesity (72.0%) and method of weight measurement (98.6%) but were less knowledgeable of ideal body weight (4.2%). The commonly known cause, complication, and management of obesity were poor diet (76.9%), hypertension (81.8%), and diet modification (86.7%), respectively. The anthropometric measures were higher among females compared to males. Prevalence of obesity was 61.3% according to WHR classification, 40.8% according to WHtR classification, 26.1% according to WC, and 14.8% according to BMI classification. Being female was significantly associated with high prevalence of obesity irrespective of the anthropometric measure used (p < 0.05). Taking of snacks in meals, eating meals late at night, physical inactivity, excessive fast food intake, and alcoholic beverage intake were associated with increased prevalence of obesity (p < 0.05). Prevalence of obesity is high among diabetic patient and thus increasing effort towards developing and making education programs by focusing on adjusting to lifestyle modifications is required. PMID- 26881263 TI - MIrExpress: A Database for Gene Coexpression Correlation in Immune Cells Based on Mutual Information and Pearson Correlation. AB - Most current gene coexpression databases support the analysis for linear correlation of gene pairs, but not nonlinear correlation of them, which hinders precisely evaluating the gene-gene coexpression strengths. Here, we report a new database, MIrExpress, which takes advantage of the information theory, as well as the Pearson linear correlation method, to measure the linear correlation, nonlinear correlation, and their hybrid of cell-specific gene coexpressions in immune cells. For a given gene pair or probe set pair input by web users, both mutual information (MI) and Pearson correlation coefficient (r) are calculated, and several corresponding values are reported to reflect their coexpression correlation nature, including MI and r values, their respective rank orderings, their rank comparison, and their hybrid correlation value. Furthermore, for a given gene, the top 10 most relevant genes to it are displayed with the MI, r, or their hybrid perspective, respectively. Currently, the database totally includes 16 human cell groups, involving 20,283 human genes. The expression data and the calculated correlation results from the database are interactively accessible on the web page and can be implemented for other related applications and researches. PMID- 26881267 TI - Investigation on Effect of Material Hardness in High Speed CNC End Milling Process. AB - This research paper analyzes the effects of material properties on surface roughness, material removal rate, and tool wear on high speed CNC end milling process with various ferrous and nonferrous materials. The challenge of material specific decision on the process parameters of spindle speed, feed rate, depth of cut, coolant flow rate, cutting tool material, and type of coating for the cutting tool for required quality and quantity of production is addressed. Generally, decision made by the operator on floor is based on suggested values of the tool manufacturer or by trial and error method. This paper describes effect of various parameters on the surface roughness characteristics of the precision machining part. The prediction method suggested is based on various experimental analysis of parameters in different compositions of input conditions which would benefit the industry on standardization of high speed CNC end milling processes. The results show a basis for selection of parameters to get better results of surface roughness values as predicted by the case study results. PMID- 26881268 TI - Angle and Context Free Grammar Based Precarious Node Detection and Secure Data Transmission in MANETs. AB - Growing attractiveness of Mobile Ad Hoc Networks (MANETs), its features, and usage has led to the launching of threats and attacks to bring negative consequences in the society. The typical features of MANETs, especially with dynamic topology and open wireless medium, may leave MANETs vulnerable. Trust management using uncertain reasoning scheme has previously attempted to solve this problem. However, it produces additional overhead while securing the network. Hence, a Location and Trust-based secure communication scheme (L&TS) is proposed to overcome this limitation. Since the design securing requires more than two data algorithms, the cost of the system goes up. Another mechanism proposed in this paper, Angle and Context Free Grammar (ACFG) based precarious node elimination and secure communication in MANETs, intends to secure data transmission and detect precarious nodes in a MANET at a comparatively lower cost. The Elliptic Curve function is used to isolate a malicious node, thereby incorporating secure data transfer. Simulation results show that the dynamic estimation of the metrics improves throughput by 26% in L&TS when compared to the TMUR. ACFG achieves 33% and 51% throughput increase when compared to L&TS and TMUR mechanisms, respectively. PMID- 26881266 TI - Differences Among Lesbian, Gay, Bisexual, Heterosexual Individuals, and those Who Reported an Other Identity on an Open-Ended Response on Levels of Social Anxiety. AB - Previous research suggests that individuals with a marginalized sexual orientation report higher levels of emotional distress (Cochran, 2001; Mayer, 2003), including higher prevalence of social anxiety (Gilman et al., 2001; Potoczniak, Aldea, & DeBlaere, 2007; Safren & Pantalone, 2006) than heterosexuals. The present study builds on previous research by examining results across sexual minority identities, including an additional write-in response option. One hundred eighty individuals participated in an online study in which they indicated their sexual orientation and completed measures of social anxiety. Results indicated that in a sample recruited in a liberal urban population, lesbian/gay, and heterosexual individuals rated similar levels of social anxiety across four Liebowitz Social Anxiety Scale subscales (fear, avoidance, social, and performance; Liebowitz, 1987). Alternatively, individuals who identified as bisexual, or indicated a write-in sexual orientation rated significantly higher levels of social anxiety than the heterosexual, and lesbian/gay groups. Findings highlight the importance of offering a write-in sexual identity option, as well as looking at differences among group experiences across sexual minorities. Future studies should investigate potential group differences in social anxiety across sexual orientations in larger samples so that comparisons can be made among subgroups of the write-in response group, as well as investigate potential contributors to these group differences. PMID- 26881265 TI - A Preliminary Comparative Assessment of the Role of CD8+ T Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis. AB - Background. CD8+ T cells have putative roles in the regulation of adaptive immune responses during infection. The purpose of this paper is to compare the status of CD8+ T cells in Multiple Sclerosis (MS) and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Methods. This preliminary investigation comprised 23 CFS/ME patients, 11 untreated MS patients, and 30 nonfatigued controls. Whole blood samples were collected from participants, stained with monoclonal antibodies, and analysed on the flow cytometer. Using the following CD markers, CD27 and CD45RA (CD45 exon isoform 4), CD8+ T cells were divided into naive, central memory (CM), effector memory CD45RA- (EM), and effector memory CD45RA+ (EMRA) cells. Results. Surface expressions of BTLA, CD127, and CD49/CD29 were increased on subsets of CD8+ T cells from MS patients. In the CFS/ME patients CD127 was significantly decreased on all subsets of CD8+ T cells in comparison to the nonfatigued controls. PSGL-1 was significantly reduced in the CFS/ME patients in comparison to the nonfatigued controls. Conclusions. The results suggest significant deficits in the expression of receptors and adhesion molecules on subsets of CD8+ T cells in both MS and CFS/ME patients. These deficits reported may contribute to the pathogenesis of these diseases. However, larger sample size is warranted to confirm and support these encouraging preliminary findings. PMID- 26881269 TI - Development of Energy Efficient Clustering Protocol in Wireless Sensor Network Using Neuro-Fuzzy Approach. AB - Wireless sensor networks (WSNs) consist of sensor nodes with limited processing capability and limited nonrechargeable battery power. Energy consumption in WSN is a significant issue in networks for improving network lifetime. It is essential to develop an energy aware clustering protocol in WSN to reduce energy consumption for increasing network lifetime. In this paper, a neuro-fuzzy energy aware clustering scheme (NFEACS) is proposed to form optimum and energy aware clusters. NFEACS consists of two parts: fuzzy subsystem and neural network system that achieved energy efficiency in forming clusters and cluster heads in WSN. NFEACS used neural network that provides effective training set related to energy and received signal strength of all nodes to estimate the expected energy for tentative cluster heads. Sensor nodes with higher energy are trained with center location of base station to select energy aware cluster heads. Fuzzy rule is used in fuzzy logic part that inputs to form clusters. NFEACS is designed for WSN handling mobility of node. The proposed scheme NFEACS is compared with related clustering schemes, cluster-head election mechanism using fuzzy logic, and energy aware fuzzy unequal clustering. The experiment results show that NFEACS performs better than the other related schemes. PMID- 26881264 TI - Immune Checkpoint Modulators: An Emerging Antiglioma Armamentarium. AB - Immune checkpoints have come to the forefront of cancer therapies as a powerful and promising strategy to stimulate antitumor T cell activity. Results from recent preclinical and clinical studies demonstrate how checkpoint inhibition can be utilized to prevent tumor immune evasion and both local and systemic immune suppression. This review encompasses the key immune checkpoints that have been found to play a role in tumorigenesis and, more specifically, gliomagenesis. The review will provide an overview of the existing preclinical and clinical data, antitumor efficacy, and clinical applications for each checkpoint with respect to GBM, as well as a summary of combination therapies with chemotherapy and radiation. PMID- 26881270 TI - Challenges of Assessing Maltreated Children Coming into Foster Care. AB - Children who have experienced early adversity have been known to be at risk of developing cognitive, attachment, and mental health problems; therefore, it is crucial that children entering foster care can be properly assessed as early as possible. There are known difficulties in assessing children in foster care, for example, in finding a reliable informant. An ongoing randomised controlled trial in Glasgow, Scotland, recruiting infants entering foster care, provides a unique opportunity to explore some of the issues which need to be considered when assessing these children. The assessment data of 70 infants entering care is described while exploring the reliability of foster carers as informants and the importance of infant engagement with tasks. This group of infants was shown to be having more problems than children from the general population. While correlations were found between a carer's level of concern about a child and the severity of a child's problem, there were still a number of children displaying worrying problem scores whom foster carers did not report concern. The child's engagement in the cognitive task showed associations with the child's attainment on the task. Findings emphasise the importance of a holistic assessment for these children and all should be considered as potential cases with Maltreatment Associated Psychiatric Problems (MAPP). PMID- 26881271 TI - Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks. AB - Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and prediction were solved by statistical models and methods. For the last two decades, a large number of Artificial Neural Networks based learning models have been proposed to solve the problems of financial data and get accurate results in prediction of the future trends and prices. This paper addressed some architectural design related issues for performance improvement through vectorising the strengths of multivariate econometric time series models and Artificial Neural Networks. It provides an adaptive approach for predicting exchange rates and it can be called hybrid methodology for predicting exchange rates. This framework is tested for finding the accuracy and performance of parallel algorithms used. PMID- 26881272 TI - Comparative Study on Various Authentication Protocols in Wireless Sensor Networks. AB - Wireless sensor networks (WSNs) consist of lightweight devices with low cost, low power, and short-ranged wireless communication. The sensors can communicate with each other to form a network. In WSNs, broadcast transmission is widely used along with the maximum usage of wireless networks and their applications. Hence, it has become crucial to authenticate broadcast messages. Key management is also an active research topic in WSNs. Several key management schemes have been introduced, and their benefits are not recognized in a specific WSN application. Security services are vital for ensuring the integrity, authenticity, and confidentiality of the critical information. Therefore, the authentication mechanisms are required to support these security services and to be resilient to distinct attacks. Various authentication protocols such as key management protocols, lightweight authentication protocols, and broadcast authentication protocols are compared and analyzed for all secure transmission applications. The major goal of this survey is to compare and find out the appropriate protocol for further research. Moreover, the comparisons between various authentication techniques are also illustrated. PMID- 26881273 TI - An Enhanced PSO-Based Clustering Energy Optimization Algorithm for Wireless Sensor Network. AB - Wireless Sensor Network (WSN) is a network which formed with a maximum number of sensor nodes which are positioned in an application environment to monitor the physical entities in a target area, for example, temperature monitoring environment, water level, monitoring pressure, and health care, and various military applications. Mostly sensor nodes are equipped with self-supported battery power through which they can perform adequate operations and communication among neighboring nodes. Maximizing the lifetime of the Wireless Sensor networks, energy conservation measures are essential for improving the performance of WSNs. This paper proposes an Enhanced PSO-Based Clustering Energy Optimization (EPSO-CEO) algorithm for Wireless Sensor Network in which clustering and clustering head selection are done by using Particle Swarm Optimization (PSO) algorithm with respect to minimizing the power consumption in WSN. The performance metrics are evaluated and results are compared with competitive clustering algorithm to validate the reduction in energy consumption. PMID- 26881274 TI - Phenotypic and Genotypic Characterization of Animal-Source Salmonella Heidelberg Isolates. AB - Salmonella enterica serotype Heidelberg (S. Heidelberg) is frequently implicated in human foodborne Salmonella infections and often produces more severe clinical disease than other serotypes. Livestock and poultry products represent a potential risk for transmission to humans. The purpose of this study was to evaluate 49 S. Heidelberg veterinary isolates for exponential growth rate (EGR), PFGE pattern, and antimicrobial resistance to evaluate these parameters as mechanisms by which S. Heidelberg emerged as a virulent foodborne pathogen. Isolates were categorized by species of origin; clinical or environmental sources; and time frame of recovery. Growth rates were determined in nutrient media using serial dilutions and colony counts; PFGE was performed according to the CDC PulseNet protocol. Minimum inhibitory concentration and susceptibility determinations were performed against antimicrobials important in human medicine. Eighteen unique PFGE patterns were detected in the isolates tested. Antimicrobial resistance was significantly greater (P < 0.05) for ten of 15 drugs in clinical over environmental isolates; for four drugs between the time frames; and for ten drugs between species of origin. The large genetic diversity present in isolates of this serotype may convey competitive advantages to this organism, while the presence of antimicrobial resistance represents a potential zoonotic risk via animal-source food products. PMID- 26881275 TI - Real-time PCR melting analysis with fiber optic SPR enables multiplex DNA identification of bacteria. AB - A fiber optic surface plasmon resonance (FO-SPR) technology was developed that enables simultaneous quantification and identification of multiple DNA targets on the same platform. The bioassay was based on the hybridization/melting of DNA coated Au nanoparticles on the FO-SPR sensor when targets are present. The multiplex concept was successfully demonstrated on two related bacteria and for detection of multiple mutations in sequences. In conclusion, FO-SPR technology shows a great potential as a next generation in vitro diagnostics tool. PMID- 26881281 TI - A 15-MHz 1-3 Piezocomposite Concave Array Transducer for Ophthalmic Imaging. AB - Because of the spherical shape of the human eye, the anterior segments of the eye, particularly the cornea and the lens, create high levels of refraction and reflection of ultrasound which negatively affect the performance of linear and convex arrays. To minimize the ultrasound energy loss, a 15-MHz concave array transducer was designed, fabricated, and characterized; its footprint is able to mesh well with the shape of the cornea. The concave array has a curvature with a radius of 15 mm and 128 elements with a 1.44- pitch. Its elevational focus and view angle are 30 mm and 72.3 degrees , respectively, thus allowing the imaging area to cover the retinal region of interest in the posterior segment. As an active layer, a 1-3 piezocomposite was designed and fabricated in response to the bidirectional (i.e., azimuthal and elevational) curvature of the concave array and the high coupling coefficient. From the performance evaluation, it was found that the completed concave array is able to provide a center frequency of 15.95 MHz and a -6-dB fractional bandwidth of 67.8% after electrical tuning has been conducted. The crosstalk level was measured to be less than -25 dB. It was verified that the concave array is robust to the refraction and reflection from the cornea through pulse-echo testing using a custom-made eye-mimicking phantom. Furthermore, images of both the wire-target phantom and the ex vivo porcine eye were acquired by the finished concave array, which was connected to a commercial ultrasound scanner equipped with a research package. The evaluation results demonstrated that the developed concave array transducer is a possible alternative to conventional arrays for effectively imaging the posterior segment of the eye. PMID- 26881277 TI - A green surfactant-assisted synthesis of hierarchical TS-1 zeolites with excellent catalytic properties for oxidative desulfurization. AB - Hierarchical TS-1 zeolites with uniform intracrystalline mesopores have been successfully synthesized through the hydrothermal method by using the green and cheap surfactant Triton X-100 as the mesoporous template. The resultant materials exhibit remarkably enhanced catalytic activity in oxidative desulfurization reactions compared to the conventional TS-1 zeolite. PMID- 26881282 TI - For love of metals. PMID- 26881276 TI - Noncompetitive affinity assays of glucagon and amylin using mirror-image aptamers as affinity probes. AB - The ability to detect picomolar concentrations of glucagon and amylin using fluorescently labeled mirror-image aptamers, so-called Spiegelmers, is demonstrated. Spiegelmers rival the specificity of antibodies and overcome the problem of biostability of natural aptamers in a biological matrix. Using Spiegelmers as affinity probes, noncompetitive capillary electrophoresis affinity assays of glucagon and murine amylin were developed and optimized. The detection limit for glucagon was 6 pM and for amylin was 40 pM. Glucagon-like peptide-1 and -2 did not interfere with the glucagon assay, while the amylin assay showed cross reactivity to calcitonin gene related peptide. The developed assays were combined with a competitive immunoassay for insulin to measure glucagon, amylin, and insulin secretion from batches of islets after incubation with different glucose concentrations. The development of these assays is an important step towards incorporation into an online measurement system for monitoring dynamic secretion from single islets. PMID- 26881284 TI - Correction. AB - Neogi T, Jansen TLTA, Dalbeth N, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2015;74:1789-98. The name of the 20th author was misspelled. The correct spelling is Janitzia Vazquez-Mellado. We regret the error. PMID- 26881283 TI - Hepatitis A infection during pregnancy. AB - QUESTION: Many of my patients are from Southeast Asia, where hepatitis A virus (HAV) infection is quite common. What precautions can I suggest my pregnant patients take before traveling to these areas and what is the risk of contracting HAV during pregnancy? ANSWER: Hepatitis A virus is a water-borne pathogen transmitted by the fecal-oral route. To reduce the risk of contracting HAV while traveling to endemic areas, it is important to maintain hygienic practices such as hand washing with safe water, particularly before handling food, avoiding drinking water or using ice cubes of unknown purity, and avoiding eating unpeeled fruits and vegetables. An HAV vaccine is available and can be administered before traveling to endemic countries. Hepatitis A virus infection has a largely favourable expected outcome even during pregnancy. Infection occurring in the second or third trimester has been reported to be associated with preterm labour. PMID- 26881286 TI - Densely Packed Lanthanide Cubane Based 3D Metal-Organic Frameworks for Efficient Magnetic Refrigeration and Slow Magnetic Relaxation. AB - Two isostructural densely packed squarato-bridged lanthanide-based 3D metal organic frameworks (MOFs) [Ln5(MU3-OH)5(MU3-O)(CO3)2(HCO2)2(C4O4)(H2O)2] [Ln = Gd (1) and Dy (2)] show giant cryogenic magnetic refrigeration (for 1) and slow magnetic relaxation (for 2). The structural analyses reveal the presence of a self-assembled crown-shaped building unit with a cubane-based rectangular moiety that leads to a special array of metal centers in 3D space in the complexes. Magnetic investigations confirm that complex 1 exhibits one of the largest cryogenic magnetocaloric effects among the molecular magnetic refrigerant materials reported so far (-DeltaSm = 64.0 J kg(-1) K(-1) for DeltaH = 9 T at 3 K). The cryogenic cooling effect (of 1) is also quite comparable with that of the commercially used magnetic refrigerant gadolinium-gallium garnet, whereas for complex 2, slow relaxation of magnetization was observed below 10 K. PMID- 26881287 TI - Statistical models for multilevel skewed physical activity data in health research and behavioral medicine. AB - OBJECTIVE: Researchers who study physical activity often use outcome variables that have a lower bound of zero and are positively skewed (e.g., minutes of physical activity in a day). Researchers also often use statistical methods that assume the outcome is normally distributed or transform the outcome as an attempt to make it more normal, both of which can be problematic. In this article, the authors describe multilevel 2-part models that use a mixture of logistic regression-to predict whether a person was active-and gamma regression-to predict amount of activity if there was activity. METHOD: The authors contrast the 2-part models to a linear multilevel model using data from a longitudinal study of physical activity (N = 113; 2,305 observations). The dependent variable was minutes of moderate-to-vigorous activity in a day and the predictor variables were day, satisfaction, and gender. RESULTS: The 2-part models outperform the linear model and provide researchers critical information that is conceptually relevant, such as distinguishing between predictors of whether activity occurred and of how much activity occurred. CONCLUSIONS: Two-part models represent a flexible and useful addition to the analysis repertoire of health researchers. To assist researchers in learning these methods, the online supplemental materials provide additional technical information as well as annotated computer code for estimating these models. (PsycINFO Database Record PMID- 26881289 TI - Additive Effects on Asymmetric Catalysis. AB - This review highlights a number of additives that can be used to make asymmetric reactions perfect. Without changing other reaction conditions, simply adding additives can lead to improved asymmetric catalysis, such as reduced reaction time, improved yield, or/and increased selectivity. PMID- 26881288 TI - Stimuli-Responsive Programmed Specific Targeting in Nanomedicine. AB - Both passive targeting and actively enhanced cellular internalization play significant roles in tumor-targeted therapy. Programmed specific targeting, as a novel targeting strategy that exploits stimuli-responsive structures, expects that nanocarriers show high stability during blood circulation for efficient passive targeting, then respond to tumor internal or external stimuli and transform into more cell-interactive forms upon arrival at the tumor tissue for enhanced cellular internalization. In this Perspective, we introduce recent advances in the design and development of stimuli-responsive programmed specific targeting nanomedicines, which are based on switchable surface charge, activatable targeting molecules, and variable coatings, to combine the advantages of passive targeting and actively enhanced cellular internalization. PMID- 26881290 TI - Meter-Long Spiral Carbon Nanotube Fibers Show Ultrauniformity and Flexibility. AB - Conventional straight fibers spun from carbon nanotubes have rather limited deformability; creating a spiral structure holds the promise to break this shape restriction and enhance structural flexibility. Here, we report up to one meter length threads containing purely single-walled nanotubes twisted into spiral loops (about 1.3 * 10(5) loops per meter) with tunable fiber diameters and electrical conductivity. Because of significant increase of the loop number and long-range homogeneity, the fibers display many unique properties (e.g., self shrinking and forming extremely entangled structure, fast stretching with great resilience, large-degree axial and lateral deflection, and excellent fatigue resistance) that are difficult to achieve in straight yarns or short helical segments. They also have potential applications as macroscopic fiber-shaped temperature sensors and deformable gas sensors. Our long spiral fibers may be configured into versatile structures such as nanotextiles for developing wearable electronics and multifunctional fabrics. PMID- 26881291 TI - Correlation of in Situ Oxazolidine Formation with Highly Synergistic Cytotoxicity and DNA Cross-Linking in Cancer Cells from Combinations of Doxorubicin and Formaldehyde. AB - Anthracyclines are a class of antitumor compounds that are successful and widely used but suffer from cardiotoxicity and acquired tumor resistance. Formaldehyde interacts with anthracyclines to enhance antitumor efficacy, bypass resistance mechanisms, improve the therapeutic profile, and change the mechanism of action from a topoisomerase II poison to a DNA cross-linker. Contrary to current dogma, we show that both efficient DNA cross-linking and potent synergy in combination with formaldehyde correlate with the anthracycline's ability to form cyclic formaldehyde conjugates as oxazolidine moieties and that the cyclic conjugates are better cross-linking agents and cytotoxins than acyclic conjugates. We also provide evidence that suggests that the oxazolidine forms in situ, since cotreatment with doxorubicin and formaldehyde is highly cytotoxic to dox resistant tumor cell lines, and that this benefit is absent in combinations of formaldehyde and epirubicin, which cannot form stable oxazolidines. These results have potential clinical implications in the active field of anthracycline prodrug design and development. PMID- 26881292 TI - Strategic balance of drug lifecycle management options differs between domestic and foreign companies in Japan. AB - INTRODUCTION: Drug approvals and patent protections are critical in drug lifecycle management (LCM) in order to maximize drug discovery investment returns. AREA COVERED: We analyzed drug LCM activities implemented by 10 top companies in Japan, focusing on drug approvals and patent term extensions. EXPERT OPINION: Foreign companies acquired numerous drug approvals primarily for new molecular entities (NMEs), while Japanese companies mainly obtained approvals for improved drugs including new indications, and intensively extended patent terms. Furthermore, we discovered three factors likely responsible for differences in drug LCM strategies of Japanese and foreign companies: research and development capacities for drugs, drug lags of foreign-origin NMEs, and cooperation between Research and Development Departments and Intellectual Property Departments. PMID- 26881293 TI - The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer. AB - INTRODUCTION: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation. AREA COVERED: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in early phase I studies. EXPERT OPINION: Among the several NTRK-inhibitors, entrectinib and LOXO 101 are those in more advanced stage of clinical development. Both agents have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring NTRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers. Results from ongoing phase II basket trials are eagerly awaited. PMID- 26881294 TI - Factors associated with quality of life in middle-aged and older patients living with HIV. AB - HIV infection has been historically considered a disease of young adults; however, adults aged 50 years and older represent now an increasing proportion of HIV cases worldwide, including in Portugal. In this context, given the considerable burden associated with living with HIV, the topic of quality-of-life (QoL) assessment has become increasingly relevant. The aims of this study were to examine the age-related differences in QoL and depressive symptoms of younger and middle-aged and older adults with HIV as well as the sociodemographic, HIV related and depressive symptoms (cognitive-affective and somatic) associated with QoL domains. The sample consisted of 1194 HIV-infected patients, recruited from 10 Portuguese hospitals. QoL data were collected using the WHOQOL-HIV-Bref questionnaire. Patients also completed the Beck Depression Inventory. Of the 1194 patients, 185 (15.5%) were over 50 years old. Middle-aged and older patients reported significantly lower QoL in the physical, independence and social relationships domains. Regarding the specific facets of QoL, middle-aged and older patients reported significantly lower scores in seven of the 29 specific facets of the WHOQOL-HIV-Bref and higher scores in one facet (financial resources). Overall, among middle-aged and older patients, higher education, being employed, a shorter time since HIV diagnosis, use of combination anti retroviral therapy and fewer depressive symptoms were significantly associated with higher QoL ratings. Our findings suggest that both cognitive-affective and somatic depressive symptoms account for significant variability in QoL scores in middle-aged and older patients. Because an important feature of healthy ageing is maintaining QoL, these data may provide useful information for tailoring age appropriate and effective interventions to improve the mental health and QoL of middle-aged and older patients living with HIV. PMID- 26881295 TI - Scanning Electronic Microscopy Evaluation of the Roughness of the Stromal Bed After Deep Corneal Cut with the LDV Femtosecond Laser (Z6) (Ziemer) and the ONE Microkeratome (Moria). AB - PURPOSE: To compare the stromal bed surface quality and the accuracy of dissection depth after deep lamellar cuts using the Leonardo Da Vinci (LDV) femtosecond laser (Z6) and the ONE Microkeratome. METHODS: Deep lamellar cuts were performed on nine human donor corneoscleral buttons: five with the LDV femtosecond (FS) laser (Z6) (Ziemer) and four with the ONE Microkeratome (MK) (Moria). Corneal thickness was measured with ultrasound pachymetry before and after the dissection. The Stromal bed quality was evaluated using light microscopy (n = 4) and scanning electron microscopy (SEM) (n = 9). The surface roughness on SEM images was graded on the scale of 1 (smoothest) to 5 (roughest) by four observers, blinded to the method used. Particle analysis on the SEM images was performed in order to have an objective measure of smoothness. RESULTS: The achieved dissection depth using the FS laser was 496.4 +/- 46.4 um when attempting 500 um and 474 +/- 60 um with the microkeratome when attempting 350 um. Histological evaluation of the corneoscleral buttons by both light and electron microscopy showed significantly smoother surface using the FS laser compared to the microkeratome. There were fewer and smaller particles observed in the SEM images of FS laser cut buttons (p < 0.001).The average observer based score of anterior surface roughness (50*) was 2.2 for the FS laser and 3.9 for the microkeratome dissections (p < 0.001). CONCLUSIONS: The LDV femtosecond laser (Z6) platform is capable of creating deep corneal lamellar dissection with smoother surface quality and with more predictable cut depth as compared to the One Microkeratome. PMID- 26881296 TI - Spatially Organized Enzymes Drive Cofactor-Coupled Cascade Reactions. AB - We report the construction of an artificial enzyme cascade based on the xylose metabolic pathway. Two enzymes, xylose reductase and xylitol dehydrogenase, were assembled at specific locations on DNA origami by using DNA-binding protein adaptors with systematic variations in the interenzyme distances and defined numbers of enzyme molecules. The reaction system, which localized the two enzymes in close proximity to facilitate transport of reaction intermediates, resulted in significantly higher yields of the conversion of xylose into xylulose through the intermediate xylitol with recycling of the cofactor NADH. Analysis of the initial reaction rate, regenerated amount of NADH, and simulation of the intermediates' diffusion indicated that the intermediates diffused to the second enzyme by Brownian motion. The efficiency of the cascade reaction with the bimolecular transport of xylitol and NAD(+) likely depends more on the interenzyme distance than that of the cascade reaction with unimolecular transport between two enzymes. PMID- 26881297 TI - Residence Times of Molecular Complexes in Solution from NMR Data of Intermolecular Hydrogen-Bond Scalar Coupling. AB - The residence times of molecular complexes in solution are important for understanding biomolecular functions and drug actions. We show that NMR data of intermolecular hydrogen-bond scalar couplings can yield information on the residence times of molecular complexes in solution. The molecular exchange of binding partners via the breakage and reformation of a complex causes self decoupling of intermolecular hydrogen-bond scalar couplings, and this self decoupling effect depends on the residence time of the complex. For protein-DNA complexes, we investigated the salt concentration dependence of intermolecular hydrogen-bond scalar couplings between the protein side-chain (15)N and DNA phosphate (31)P nuclei, from which the residence times were analyzed. The results were consistent with those obtained by (15)Nz-exchange spectroscopy. This self decoupling-based kinetic analysis is unique in that it does not require any different signatures for the states involved in the exchange, whereas such conditions are crucial for kinetic analyses by typical NMR and other methods. PMID- 26881298 TI - Facile Use of Cationic Hydrogel Particles for Surface Modification of Planar Substrates Toward Multifunctional Neural Permissive Surfaces: An in Vitro Investigation. AB - Synthetic materials such as silicon have been commonly used for neural interfacing applications but are intrinsically noninteractive with neurons. Here, a facile approach has been developed to integrate both chemical and topographical cues to impart neural permissiveness for such materials. The approach simply exploits the basic phenomenon of electrostatically driven adsorption of colloidal particles onto a solid material and applies it to a cationic hydrogel particle system that we have developed recently based on "click" reaction of epoxide and amine. The particle adsorption process can be tuned by varying the adsorption time and the concentration of the original colloidal suspension, both of which directly control the surface densities of the adsorbed hydrogel particles. Using the PC12 cell line and primary cortical neurons derived from chick embryo, we demonstrate that the particle-adsorbed surface readily supports robust cell adhesion and differentiation. Although the extent of neural permissiveness exhibited by such particle-adsorbed surface was comparable to the cationic polyethylenimine-coated control surface, the adsorbed hydrogel particles offer a unique reservoir function to the modified surface that is unparalleled by the control. The successful loading of hydrophobic dye of nile red to the surface adsorbed hydrogel particles indicates that the modified surface not only provides physical support of neurons, but also can be explored in the future to exert localized therapeutic actions favorable for neural interfacing. PMID- 26881300 TI - Conducting Carbon Dot-Polypyrrole Nanocomposite for Sensitive Detection of Picric acid. AB - We report the conducting nature of carbon dots (Cdots) synthesized from citric acid and ethylene diamine. Chemically synthesized conducting nanocomposite consisting of Cdots and polypyrrole (PPy) is further reported, which showed higher electrical conductiviy in comparison to the components i.e., Cdots or PPy. The conductive film of the composite material was used for highly sensitive and selective detection of picric acid in water as well as in soil. To the best of our knowledge, this is the first report on the conductivity based sensing application of Cdot nanocomposite contrary to the traditional fluorescence based sensing approaches. PMID- 26881299 TI - Alginate Sulfates Mitigate Binding Kinetics of Proangiogenic Growth Factors with Receptors toward Revascularization. AB - Ever since proangiogenic growth factors have been used as a vascular medicine to treat tissue ischemia, efforts have been increasingly made to develop a method to enhance efficacy of growth factors in recreating microvascular networks, especially at low dose. To this end, we hypothesized that polysaccharides substituted with sulfate groups would amplify growth factor receptor activation and stimulate phenotypic activities of endothelial cells involved in neovascularization. We examined this hypothesis by modifying alginate with a controlled number of sulfates and using it to derive a complex with vascular endothelial growth factor (VEGF), as confirmed with fluorescence resonance energy transfer (FRET) assay. Compared with the bare VEGF and with a mixture of VEGF and unmodified alginates, the VEGF complexed with alginate sulfates significantly reduced the dissociation rate with the VEGFR-2, elevated VEGFR-2 phosphorylation level, and increased the number of endothelial sprouts in vitro. Furthermore, the VEGF-alginate sulfate complex improved recovery of perfusion in an ischemic hindlimb of a mouse due to the increase of the capillary density. Overall, this study not only demonstrates an important cofactor of VEGF but also uncovers an underlying mechanism by which the cofactor mitigates the VEGF-induced signaling involved in the binding kinetics and activation of VEGFR. We therefore believe that the results of this study will be highly useful in improving the therapeutic efficacy of various growth factors and expediting their uses in clinical treatments of wounds and tissue defects. PMID- 26881302 TI - The foundational principles as psychological lodestars: Theoretical inspiration and empirical direction in rehabilitation psychology. AB - Historically, the Foundational Principles articulated by Wright (1983) and others guided theory development, research and scholarship, and practice in rehabilitation psychology. In recent decades, these principles have become more implicit and less explicit or expressive in the writings and work of rehabilitation professionals. We believe that the Foundational Principles are essential lodestars for working with people with disabilities that can guide inquiry, practice, and service. To introduce this special issues, this commentary identifies and defines key Foundational Principles, including, for example, Lewin's (1935) person-environment relation, adjustment to disability, the malleability of self-perceptions of bodily states, and the importance of promoting dignity for people with disabilities. We then consider the role the Foundational Principles play in the articles appearing in this special issue. We close by considering some new principles and their potential utility in rehabilitation settings. Readers in rehabilitation psychology and aligned areas (e.g., social-personality psychology, health psychology, rehabilitation therapist, psychiatry, and nursing) are encouraged to consider how the Foundational Principles underlie and can shape their research and practice. PMID- 26881301 TI - A Case Study of the Neti Pot's Rise, Americanization, and Rupture as Integrative Medicine in U.S. Media Discourse. AB - In a period of only one decade in the United States, the neti pot shifted from obscure Ayurvedic health device to mainstream complementary and integrative medicine (CIM), touted by celebrities and sold widely in drug stores. We examine the neti pot as a case study for understanding how a foreign health practice became mainstreamed, and what that process reveals about more general discourses of health in the United States. Using discourse analysis of U.S. popular press and new media news (1999-2012) about the neti pot, we trace the development of discourses from neti's first introduction in mainstream news, through the hype following Dr. Oz's presentation on Oprah, to 2011 when two adults tragically died after using Naegleria fowleri amoeba-infested tap water in their neti pots. Neti pot discourses are an important site for communicative analysis because of the pot's complexity as an intercultural artifact: Neti pots and their use are enfolded into the biomedical practice of nasal irrigation and simultaneously Orientalized as exotic/magical and suspect/dangerous. This dual positioning as normal and exotic creates inequitable access for using the neti pot as a resource for increasing cultural health capital (CHC). This article contributes to work that critically theorizes the transnationalism of CIM, as the neti pot became successfully Americanized. These results have implications for understanding global health practices' incorporation or co-optation in new contexts, and the important role that popularly mediated health communication can play in framing what health care products and practices mean for consumers. PMID- 26881304 TI - Predicting quality of life in adults with severe mental illness: Extending the International Classification of Functioning, Disability, and Health. AB - PURPOSE/OBJECTIVE: The International Classification of Functioning, Disability and Health (ICF) framework was used to investigate person-environment contextual factors, mental functioning, activity limitations, and participation as predictors of quality of life (QoL) in adults with severe mental illness (SMI). RESEARCH METHOD/DESIGN: A quantitative descriptive design using multiple regression and correlational analyses was used. One hundred ninety-four individuals with SMI from 4 community-based mental health agencies in 2 states from Southern and Midwestern regions of the United States participated in the study. The criterion variable was QoL. Predictor variables comprised the ICF constructs: (a) demographics, (b) personal factors, (c) environmental factors, (d) mental functioning, (e) activity limitations, and (f) participation. RESULTS: A majority of participants were White (60.3%) and not employed (59.8%). Half of them received Social Security Disability Income and/or Supplemental Security Income (50.0%). Correlations between QoL and the predictor variables ranged from small to large (r = .01 to .63, respectively). The final regression model accounted for 58% of the variance in QoL. After controlling for other factors, social competency, social support, societal stigma, psychological distress, cognitive dysfunction, activity limitations, and participation were found to be significant predictors of QoL in adults with SMI. CONCLUSIONS/IMPLICATIONS: The study supports the use of the ICF to predict QoL for adults with SMI. Evidence based treatments focused on increasing social competence, social support, and participation should be developed to promote rehabilitation outcomes and overall QoL. PMID- 26881305 TI - Application of well-being therapy to people with disability and chronic illness. AB - PURPOSE/OBJECTIVE: Research data clearly indicate most people living with a disability return to premorbid levels of psychological functioning. However, some individuals living with a disability are vulnerable for the development of psychological disorders including depression, anxiety, and posttraumatic stress disorder. Rather than understanding this phenomenon of vulnerability solely as the presence of psychopathology, it can be understood from a positive psychology standpoint as a deficit of well-being. We extend this approach by demonstrating the links between the historic foundational principles of rehabilitation psychology and the relevant current research on psychology of well-being. The article then explores the implications of providing meaningful interventions that could improve the lives of persons living with disability and chronic illness. RESULTS: Based on this view, well-being therapy is proposed as an intervention because it has proven efficacy in acting as a buffer against the development of some negative affective states. The assumptions and dimensions underlying this approach are shown to be relevant to both persons living with disability and to the foundational principles of rehabilitation psychology. A model for assisting people with disability in improving their well-being and decreasing negative aspects of their life by balancing factors relevant to well-being is discussed. CONCLUSIONS/IMPLICATIONS: The authors conclude by exploring the benefits of engendering positive well-being versus the traditional focus on solely alleviating negative affective states. PMID- 26881303 TI - Resilience and vulnerability in individuals with chronic pain and physical disability. AB - OBJECTIVE: To examine the independent contributions of vulnerability and resilience factors to pain interference, self-efficacy for managing pain, global mental health, and global physical health. RESEARCH METHOD/DESIGN: Secondary analysis of baseline data from individuals with a spinal cord injury (n = 73), amputation (n = 33), or multiple sclerosis (n = 82) and chronic pain who participated in a randomized controlled trial comparing 2 chronic pain interventions. Participants completed a comprehensive battery of pain-related outcomes that assessed for both psychosocial assets and maladaptive cognitions and behaviors. RESULTS: Results suggested that vulnerability and resilience factors together account for a considerable amount of variance in the physical outcomes, but that neither set of factors was able to make a substantial contribution above and beyond the other. In contrast, for mental health related outcomes, results indicated that resilience factors did make a meaningful contribution above and beyond vulnerability factors, suggesting the important contribution of resilience factors to the psychological experience of chronic pain. CONCLUSIONS: The present study suggested a valuable contribution of both resilience and vulnerability factors to pain outcomes, with the additional caveat that resilience factors uniquely impact specific outcomes-particularly those that are more psychosocially focused-above and beyond vulnerability factors. Taken together, this highlights the importance of considering resilience factors in addition to vulnerability factors for individuals with chronic pain. Additional research is needed to explore other factors that could be considered representative of the resilience construct and more attention should be focused on evaluating the effects of interventions that seek to build an individual's assets. PMID- 26881306 TI - The unfairness of it all: Exploring the role of injustice appraisals in rehabilitation outcomes. AB - OBJECTIVE: A fundamental principle of rehabilitation psychology is that individual appraisals of the social and physical environment-including injury itself-have profound consequences for coping and adjustment. When core assumptions of a just and predictable world are violated and accompanied by ostensibly undeserved suffering and loss, perceptions of injustice can arise. Given the role of appraisal processes in adjustment to disability, mounting empirical support, and absence of targeted interventions, the current article considers perceptions of injustice regarding personal injury/disability as a fundamental appraisal affecting rehabilitation outcomes. RESEARCH METHOD: The authors review theory underpinning the relevance of injustice appraisals and critically examine existing literature regarding the impact of perceived injustice and related constructs (i.e., attribution of blame, anger, and belief in a just world) on adjustment following injury. RESULTS: The authors bring attention to perceptions of injustice regarding personal injury/disability as a fundamental appraisal affecting rehabilitation outcomes. Dimensions of the social environment that have not received substantial attention in current research on condition-related injustice appraisals are highlighted. IMPLICATIONS: Perceived injustice is a potentially central appraisal process to physical and psychological outcomes in the context of rehabilitation. Research regarding the role of perceived injustice, related constructs, and potential social/environmental modulators of injustice perception is still in its infancy. Guided buy its foundational principles, the field of rehabilitation psychology can broaden and shape inquiry regarding perceived injustice. This article aims to guide future research, offer concepts for key areas of discourse, and consider potential interventions in the rehabilitation psychology domain. PMID- 26881307 TI - Teaching the foundational principles of rehabilitation psychology. AB - OBJECTIVE: Wright (1983) described 20 "value-laden beliefs and principles" that form the foundational principles of rehabilitation psychology, and the education and training of rehabilitation psychologists necessitates that they acquire the specialty-specific knowledge and attitudes/values related to these principles. This article addresses 2 questions about how these principles can be taught in rehabilitation psychology training: (a) What are the core theories and evidence supporting these foundational principles, and what should be the content of a "core curriculum" for teaching these?; and (b) What is known about the most effective methods for teaching these foundational principles, including questions of how to teach values? METHOD: The foundational principles were grouped into 3 categories: individual psychological processes, social psychological processes, and values related to social integration. A literature review was conducted in these 3 categories, and the results are summarized and discussed. RESULTS: A core curriculum is discussed for teaching about disability-specific individual psychological processes, social psychological processes, and values related to social integration, including methods to reduce group prejudice and promote values relevant to the foundational principles. Specific suggestions for training program content and methods are provided. CONCLUSIONS: It is hoped that effective teaching of Wright's (1983) value-laden beliefs and principles will help rehabilitation psychology trainers and trainees focus on the key knowledge and attitude-value competencies that are to be acquired in training. PMID- 26881308 TI - Globalizing rehabilitation psychology: Application of foundational principles to global health and rehabilitation challenges. AB - PURPOSE/OBJECTIVE: This article reviewed foundational principles in rehabilitation psychology and explored their application to global health imperatives as outlined in the World Report on Disability (World Health Organization & World Bank, 2011). RESEARCH METHOD/DESIGN: Historical theories and perspectives are used to assist with conceptual formulation as applied to emerging international rehabilitation psychology topics. RESULTS: According to the World Report on Disability (World Health Organization & World Bank, 2011), there are approximately 1 billion individuals living with some form of disability globally. An estimated 80% of persons with disabilities live in low- to middle income countries (WHO, 2006). The primary messages and recommendations of the World Report on Disability have been previously summarized as it relates to potential opportunities for contribution within the field of rehabilitation psychology (MacLachlan & Mannan, 2014). Yet, undeniable barriers remain to realizing the full potential for contributions in low- to middle-income country settings. CONCLUSIONS/IMPLICATIONS: A vision for engaging in international capacity building and public health efforts is needed within the field of rehabilitation psychology. Foundational rehabilitation psychology principles have application to the service of individuals with disabilities in areas of the world facing complex socioeconomic and sociopolitical challenges. Foundational principles of person-environment interaction, importance of social context, and need for involvement of persons with disabilities can provide guidance to the field as it relates to global health and rehabilitation efforts. The authors illustrate the application of rehabilitation psychology foundational principles through case examples and description of ongoing work, and link foundational principles to discreet domains of intervention going forward. PMID- 26881309 TI - Supervision in rehabilitation psychology: Application of Beatrice Wright's value laden beliefs and principles. AB - Clinical supervision is of critical importance for training subsequent generations of psychologists. Specialty training in rehabilitation psychology requires exposure to specific knowledge, skills, and attitudes related to disability and specialized supervision and mentorship. In the literature to date, minimal guidance exists regarding supervision training and methods specifically for rehabilitation psychologists. This article aims to provoke discussion regarding supervision practice and dissemination of the values fundamental to our specialty. The foundational wisdom of Dr. Beatrice Wright (1983) is applied for the purposes of this endeavor. Examples of clinical supervision scenarios are presented as teaching vignettes to demonstrate ways in which supervisors and mentors can incorporate this content, promote discussion, and apply it to real world practice. PMID- 26881310 TI - Clinical utility and measurement characteristics of the Hospital Anxiety and Depression Scale for individuals with traumatic brain injury. AB - This Rehabilitation Measures Database summary provides a review of the psychometric properties of the HADS in individuals with TBI. A full review of the HADS as well as reviews of over 330 other instruments can be found at www.rehabmeasures.org. PMID- 26881312 TI - Experimental Solubility Approach to Determine PDMS-Water Partition Constants and PDMS Activity Coefficients. AB - Freely dissolved aqueous concentration and chemical activity are important determinants of contaminant transport, fate, and toxic potential. Both parameters are commonly quantified using Solid Phase Micro-Extraction (SPME) based on a sorptive polymer such as polydimethylsiloxane (PDMS). This method requires the PDMS-water partition constants, KPDMSw, or activity coefficient to be known. For superhydrophobic contaminants (log KOW >6), application of existing methods to measure these parameters is challenging, and independent measures to validate KPDMSw values would be beneficial. We developed a simple, rapid method to directly measure PDMS solubilities of solid contaminants, SPDMS(S), which together with literature thermodynamic properties was then used to estimate KPDMSw and activity coefficients in PDMS. PDMS solubility for the test compounds (log KOW 7.2-8.3) ranged over 3 orders of magnitude (4.1-5700 MUM), and was dependent on compound class. For polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs), solubility-derived KPDMSw increased linearly with hydrophobicity, consistent with trends previously reported for less chlorinated congeners. In contrast, subcooled liquid PDMS solubilities, SPDMS(L), were approximately constant within a compound class. SPDMS(S) and KPDMSw can therefore be predicted for a compound class with reasonable robustness based solely on the class-specific SPDMS(L) and a particular congener's entropy of fusion, melting point, and aqueous solubility. PMID- 26881313 TI - Sleep quality influences subsequent motor skill acquisition. AB - While the influence of sleep on motor memory consolidation has been extensively investigated, its relation to initial skill acquisition is less well understood. The purpose of the present study was to investigate the influence of sleep quality and quantity on subsequent motor skill acquisition in young adults without sleep disorders. Fifty-five healthy adults (mean age = 23.8 years; 34 women) wore actigraph wristbands for 4 nights, which provided data on sleep patterns before the experiment, and then returned to the laboratory to engage in a motor sequence learning task (explicit 5-item finger sequence tapping task). Indicators of sleep quality and quantity were then regressed on a measure of motor skill acquisition (Gains Within Training, GWT). Wake After Sleep Onset (WASO; i.e., the total amount of time the participants spent awake after falling asleep) was significantly and negatively related to GWT. This effect was not because of general arousal level, which was measured immediately before the motor task. Conversely, there was no relationship between GWT and sleep duration or self-reported sleep quality. These results indicate that sleep quality, as assessed by WASO and objectively measured with actigraphy before the motor task, significantly impacts motor skill acquisition in young healthy adults without sleep disorders. (PsycINFO Database Record PMID- 26881311 TI - Obesity-Dependent Increases in Oocyte mRNAs Are Associated With Increases in Proinflammatory Signaling and Gut Microbial Abundance of Lachnospiraceae in Female Mice. AB - RNAs stored in the metaphase II-arrested oocyte play important roles in successful embryonic development. Their abundance is defined by transcriptional activity during oocyte growth and selective degradation of transcripts during LH induced oocyte maturation. Our previous studies demonstrated that mRNA abundance is increased in mature ovulated oocytes collected from obese humans and mice and therefore may contribute to reduced oocyte developmental competence associated with metabolic dysfunction. In the current study mouse models of diet-induced obesity were used to determine whether obesity-dependent increases in proinflammatory signaling regulate ovarian abundance of oocyte-specific mRNAs. The abundance of oocyte-specific Bnc1, Dppa3, and Pou5f1 mRNAs as well as markers of proinflammatory signaling were significantly increased in ovaries of obese compared with lean mice which were depleted of fully grown preovulatory follicles. Chromatin-immunoprecipitation analyses also demonstrated increased association of phosphorylated signal transducer and activator of transcription 3 with the Pou5f1 promoter in ovaries of obese mice suggesting that proinflammatory signaling regulates transcription of this gene in the oocyte. The cecum microbial content of lean and obese female mice was subsequently examined to identify potential relationships between microbial composition and proinflammatory signaling in the ovary. Multivariate Association with Linear Models identified significant positive correlations between cecum abundance of the bacterial family Lachnospiraceae and ovarian abundance of Tnfa as well as Dppa3, Bnc1, and Pou5f1 mRNAs. Together, these data suggest that diet-induced changes in gut microbial composition may be contributing to ovarian inflammation which in turn alters ovarian gene expression and ultimately contributes to obesity-dependent reduction in oocyte quality and development of infertility in obese patients. PMID- 26881314 TI - Differential influence of social versus isolate housing on vicarious fear learning in adolescent mice. AB - Laboratory rodents can adopt the pain or fear of nearby conspecifics. This phenotype conceptually lies within the domain of empathy, a bio-psycho-social process through which individuals come to share each other's emotion. Using a model of cue-conditioned fear, we show here that the expression of vicarious fear varies with respect to whether mice are raised socially or in solitude during adolescence. The impact of the adolescent housing environment was selective: (a) vicarious fear was more influenced than directly acquired fear, (b) "long-term" (24-h postconditioning) vicarious fear memories were stronger than "short-term" (15-min postconditioning) memories in socially reared mice whereas the opposite was true for isolate mice, and (c) females were more fearful than males. Housing differences during adolescence did not alter the general mobility of mice or their vocal response to receiving the unconditioned stimulus. Previous work with this mouse model underscored a genetic influence on vicarious fear learning, and the present study complements these findings by elucidating an interaction between the adolescent social environment and vicarious experience. Collectively, these findings are relevant to developing models of empathy amenable to mechanistic exploitation in the laboratory. (PsycINFO Database Record PMID- 26881315 TI - Charge-Neutral Constant pH Molecular Dynamics Simulations Using a Parsimonious Proton Buffer. AB - In constant pH molecular dynamics simulations, the protonation states of titratable sites can respond to changes of the pH and of their electrostatic environment. Consequently, the number of protons bound to the biomolecule, and therefore the overall charge of the system, fluctuates during the simulation. To avoid artifacts associated with a non-neutral simulation system, we introduce an approach to maintain neutrality of the simulation box in constant pH molecular dynamics simulations, while maintaining an accurate description of all protonation fluctuations. Specifically, we introduce a proton buffer that, like a buffer in experiment, can exchange protons with the biomolecule enabling its charge to fluctuate. To keep the total charge of the system constant, the uptake and release of protons by the buffer are coupled to the titration of the biomolecule with a constraint. We find that, because the fluctuation of the total charge (number of protons) of a typical biomolecule is much smaller than the number of titratable sites of the biomolecule, the number of buffer sites required to maintain overall charge neutrality without compromising the charge fluctuations of the biomolecule, is typically much smaller than the number of titratable sites, implying markedly enhanced simulation and sampling efficiency. PMID- 26881316 TI - Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism. AB - We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay. Six single nucleotide polymorphisms, 2 in the VDR gene (rs731236 TC and rs12721377 AG) and 4 in the GC gene (rs2282679 AC, rs4588 CA, rs7041 GT, and rs2298849 TC), were genotyped by real-time polymerase chain reaction. We found that the rs7041 minor allele (G) and rare genotype (GG) were associated with higher BMI (p = 0.007 and p = 0.012, respectively), but they did not influence 25OHD3 levels. However, the minor alleles of rs2282679 (A) and rs4588 (C) were associated with low 25OHD3 plasma levels (p = 0.039 and p = 0.021, respectively), but not with BMI. Having categorized the subjects based on their sex, we found that (i) rs7041 GG associated with high BMI in females (p = 0.003), (ii) rs4588 CC associated with high BMI in females (p = 0.034) and low 25OHD3 levels in males (p = 0.009), and (iii) rs12721377 AA associated with low 25OHD3 levels in females (p = 0.039). Notably, none of the common haplotypes (6 in the GC gene and 3 in the VDR gene) were associated with BMI. Therefore, polymorphisms in the GC (rs2282679, rs4588, rs7041) and VDR (rs12721377) genes were independently associated with obesity and 25OHD3 levels with a clear sex dimorphism. PMID- 26881317 TI - Effects of aerobic training, resistance training, or both on cardiorespiratory and musculoskeletal fitness in adolescents with obesity: the HEARTY trial. AB - The purpose of this study was to examine the effects of aerobic, resistance, and combined exercise training on cardiorespiratory and musculoskeletal fitness in postpubertal adolescents with obesity. After a 4-week supervised moderate intensity exercise run-in, 304 adolescents aged 14-18 years with body mass index >=85th percentile were randomized to 4 groups for 22 weeks of aerobic training, resistance training, combined training, or a nonexercising control. All participants received dietary counselling with a maximum daily energy deficit of 250 kcal. Cardiorespiratory fitness (peak oxygen consumption) was measured by indirect calorimetry using a graded treadmill exercise test. Musculoskeletal fitness was measured using the 2003 Canadian Physical Activity Fitness and Lifestyle Appraisal tests (hand grip, push-ups, partial curl-ups, sit and reach, and vertical jump). Muscular strength was assessed using an 8-repetition maximum test on the bench press, seated row, and leg press machines. A greater increase in peak oxygen consumption in the aerobic exercise group (30.6 +/- 0.6 to 33.4 +/ 0.7 mLO2/kg/min) was measured relative to the control group (30.6 +/- 0.5 to 30.9 +/- 0.7 mLO2/kg/min) (p = 0.002). Similarly, the number of partial curl-ups increased in the aerobic group (19 +/- 1 to 23 +/- 1) while no differences were measured in the control group (19 +/- 1 to 20 +/- 1) (p = 0.015). Increases in muscular strength and number of push-ups were greatest in the resistance group versus the control and combined groups versus the aerobic group (p < 0.05). In conclusion, aerobic training had the strongest effect on cardiorespiratory fitness, while resistance and combined training improved both muscular strength and endurance more than control and aerobic training alone, respectively, in adolescents with obesity. PMID- 26881318 TI - Holding on while letting go: trauma and growth on the pathway of dementia care in families. AB - OBJECTIVES: Limited research explores the medical model of residential care in dementia from the family caregiver's perspectives. METHOD: This study sought subjective interpretations of nine family caregivers who experienced relinquishing their status as primary caregiver to a medical model, dementia care residential setting. Following semi-structured interviews and transcription data was analysed using interpretative phenomenological analysis. RESULTS: One superordinate theme, navigating 'system' control, overarched three subordinate themes: connecting/disconnecting, windows closing, and capacity for sensation. Navigating system control reflected participants' experience of circumnavigating a medical system fraught with hierarchical challenges inclusive of a complex maze of contradictions that appeared threatening, yet appeared comforting; authoritarian, yet often humane. For them, care of self, while advocating for a family member with dementia, required vigilance to manoeuvre a system of care that imposed its uninvited authority at will. Connection/disconnection highlights the enduring struggle for inclusivity in caregiving despite the omnipresent trauma of windows closing. Psychological growth came to these participants through an unexpected capacity for sensation which offered a unique lens to communication with the family member with dementia primarily through sensory exchange. CONCLUSIONS: Models of dementia care and therapeutic interventions could inclusively involve dementia family caregivers who may be experiencing traumatic distress, and associated guilt, stigma, loss, and grief. Co-existing psychological wellbeing, however, is possible when family members are encouraged to transition communication to sensory awareness and exchange as windows close. PMID- 26881319 TI - Case-mix adjustment for diabetes indicators: a systematic review. AB - OBJECTIVES: Case-mix adjustment is generally considered indispensable for fair comparison of healthcare performance. Inaccurate results are also unfair to patients as they are ineffective for improving quality. However, little is known about what factors should be adjusted for. We reviewed case-mix factors included in adjustment models for key diabetes indicators, the rationale for their inclusion, and their impact on performance. STUDY DESIGN: Systematic review. METHODS: This systematic review included studies published up to June 2013 addressing case-mix factors for 6 key diabetes indicators: 2 outcomes and 2 process indicators for glycated hemoglobin (A1C), low-density lipoprotein cholesterol, and blood pressure. Factors were categorized as demographic, diabetes-related, comorbidity, generic health, geographic, or care-seeking, and were evaluated on the rationale for inclusion in the adjustment models, as well as their impact on indicator scores and ranking. RESULTS: Thirteen studies were included, mainly addressing A1C value and measurement. Twenty-three different case-mix factors, mostly demographic and diabetes-related, were identified, and varied from 1 to 14 per adjustment model. Six studies provided selection motives for the inclusion of case-mix factors. Marital status and body mass index showed a significant impact on A1C value. For the other factors, either no or conflicting associations were reported, or too few studies (n <= 2) investigated this association. CONCLUSIONS: Scientific knowledge about the relative importance of case-mix factors for diabetes indicators is emerging, especially for demographic and diabetes-related factors and indicators on A1C, but is still limited. Because arbitrary adjustment potentially results in inaccurate quality information, meaningful stratification that demonstrates inequity in care might be a better guide, as it can be a driver for quality improvement. PMID- 26881320 TI - The effect of Medicare Advantage enrollment on mammographic screening. AB - OBJECTIVES: To compare the rates of mammographic screening and reasons for not receiving mammography between Medicare Advantage (MA) and Medicare fee-for service (FFS) beneficiaries. STUDY DESIGN: Cross-sectional study. METHODS: Unadjusted rates of mammographic screening and reasons for not receiving mammography were compared between MA and FFS beneficiaries in total and within subgroups. Probabilities of mammographic screening were also compared between the MA and FFS beneficiaries after adjusting for age, education, race/ethnicity, health status, marriage status, and region of residence using modified Poisson regression models. RESULTS: We found significantly higher unadjusted rates of mammographic screening in the MA beneficiary population compared with the FFS population (50.3% vs 44%, respectively; P < .0001). MA beneficiaries were more likely to receive a mammogram than FFS beneficiaries (unadjusted relative risk [RR], 1.13; 95% CI, 1.07-1.19; and adjusted RR, 1.06; 95% CI, 1.01-1.12). Furthermore, the top 6 reasons why MA and FFS beneficiaries did not receive mammograms were: "not needed," "doctor did not recommend," "forgot," "not recommended annually," "did not like mammograms," and "appointment due soon." Among non-Hispanic blacks and Hispanics specifically, FFS beneficiaries were more likely to report doctors not recommending mammograms than MA beneficiaries. CONCLUSIONS: MA beneficiaries were 1.06 times more likely to receive mammography screening compared with the FFS population. Additionally, providers were less likely to recommend mammographic screening to non-Hispanic black and Hispanic FFS beneficiaries compared with non-Hispanic black and Hispanic MA beneficiaries. PMID- 26881321 TI - Molecular testing patterns in metastatic non-small cell lung cancer. AB - OBJECTIVES: Identification of oncogene mutations and gene rearrangements in individuals with non-small cell lung cancer (NSCLC) can help identify candidates for targeted therapy. This study examined whether clinicians are ordering molecular testing for patients with metastatic NSCLC (mNSCLC) prior to therapy initiation. STUDY DESIGN: Members from a national health plan with lung cancer and metastatic disease were followed retrospectively. METHODS: Members were identified in medical claims data from January 1, 2010, to December 31, 2012, if they had 2 or more claims for lung cancer (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 162.xx) and metastatic disease (>= 1 claim with ICD-9-CM code 196.xx-198.xx) who were continuously enrolled in a fully insured plan 180 days prior to index date. Patients were excluded if they had a history of chemotherapy used primarily in small cell lung cancer, or a medical claim associated with an unrelated malignancy. The timing of molecular testing was compared with the start of chemotherapy and targeted therapy, if applicable. RESULTS: A total of 2623 patients presumed to have mNSCLC were included for analysis; of whom, 52.5% were male with a mean age of 72.5 years (SD = 8.2 years). A total of 1597 (60.9%) patients had a Current Procedural Terminology code associated with molecular testing at any time in their claims history. Of the 733 patients with molecular testing and chemotherapy or targeted therapy claims, testing occurred prior to systemic therapy initiation in 651 (88.8%; 95% CI, 86.1%-90.9%) patients. The median time between testing and therapy initiation was 38 days (interquartile range = 23-69 days). CONCLUSIONS: Assessment of oncogene mutations and gene rearrangements in mNSCLC routinely occurs prior to treatment initiation as suggested by analyses of claims data from a large US health plan. Validation using patient medical records is needed. PMID- 26881322 TI - Inappropriate ordering of lumbar spine magnetic resonance imaging: are providers Choosing Wisely? AB - OBJECTIVES: To analyze inappropriate use of magnetic resonance imaging (MRI) for patients with low back pain in a healthcare system with no financial incentives for overuse. STUDY DESIGN: We used administrative data to assess the appropriateness of lumbar spine (LS) MRI in the Veterans Health Administration. METHODS: All veterans who received LS MRI in the outpatient setting in fiscal year 2012 were included. We based our assessments of appropriateness on CMS criteria, which have been endorsed by the National Quality Forum. Generalized estimating equations were used to evaluate characteristics of inappropriate scans. RESULTS: Of the 110,661 LS MRIs performed, 31% were classified as inappropriate. Most scans that were considered appropriate were characterized as such because they were preceded by conservative therapy (53%). "Red flag" conditions were responsible for a much smaller percentage of scans being considered appropriate; 13% of scans were preceded by conservative therapy and were performed in patients with a red flag condition, while only 4% of scans were considered appropriate because of red flag conditions only. Scans ordered in the emergency department and in urgent care, primary care, and internal medicine clinics were most likely to be classified as inappropriate. Resident physicians were significantly less likely than other provider types to order inappropriate LS MRIs (odds ratio, 0.80; P < .0001). Approximately 24% of providers ordered 74% of inappropriate scans. CONCLUSIONS: We found that 31% of LS MRIs were inappropriate in a healthcare system largely absent of financial and other incentives for ordering. The problem of inappropriate ordering of LS MRI is concentrated in a small number of providers; any provider-facing interventions to reduce inappropriate order should therefore be targeted, rather than aimed at all providers who order LS MRI. PMID- 26881323 TI - USPSTF colorectal cancer screening guidelines: an extended look at multi-year interval testing. AB - OBJECTIVES: The US Preventive Services Task Force (USPSTF) released draft recommendations regarding colorectal cancer (CRC) screening in October 2015. Despite evidence that annual fecal blood testing test use is uncommon in screen eligible adults, with only 10.4% reporting the use of such a test in 2012, and features poor adherence over time, the USPSTF recommended only 3 noninvasive screening strategy options, all including annual fecal occult blood testing: 1) annual fecal immunochemical test (FIT) alone; 2) annual FIT in combination with flexible sigmoidoscopy every 10 years; and 3) annual high-sensitivity fecal occult blood test (hsFOBT). Mt-sDNA is the only FDA-approved CRC screening test, is covered by Medicare every 3 years, and is included as an every-3-year (3y) option in the American Cancer Society guidelines. We demonstrate that USPSTF modeling includes an embedded sensitivity analysis of less frequent than annual test adherence, which provides support for the inclusion of mt-sDNA 3y as a recommended test. STUDY DESIGN: A descriptive analysis of USPSTF modeling of the clinical impact of various stool based CRC screening strategies. METHODS: We analyzed the data generated by the USPSTF CRC screening models describing the impact of noninvasive CRC screening strategies on CRC incidence, CRC related mortality, life years gained (LYG), colonoscopy volume and associated complication, test efficiency (a measure of benefits (LYG) and harms (colonoscopies generated), and identified strategies that provide 90% or more of the LYG by screening with colonoscopy every 10 years. We compared mt-sDNA at 3y intervals and FIT and hsFOBT at 2-year (2y) and 3y intervals and did not consider annual testing. RESULTS: We found that only mt-sDNA 3y, FIT 2y, and FIT 3y were within 98% of the efficiency frontier. However, only mt-sDNA 3y generates more than 90% of the life-years gained with screening colonoscopy. These results meet the USPSTF criteria for a recommendation for mt-sDNA 3y for routine screening. CONCLUSIONS: Given poor adherence to annual testing, any screening opportunity with a test, such as mt-sDNA, that has high sensitivity for CRC and for the most significant precancerous lesions would be an important screening option for patients for maximizing screening effectiveness in reducing CRC incidence and mortality. PMID- 26881324 TI - Auditory processing abilities in children with chronic otitis media with effusion. AB - CONCLUSION: The study results indicate that children with a history of otitis media with effusion (OME) suffer from auditory processing disorder to some degree. The findings support the hypothesis that fluctuating hearing loss may affect central auditory processing during critical periods. OBJECTIVES: Evidence suggests that prolonged OME in children can result in an auditory processing disorder, presumably because hearing has been disrupted during an important developmental period. A lack of auditory stimulation leads to the abnormal development of the hearing pathways in the brain. The aim of the present study was to determine the effects of OME on binaural auditory function and auditory temporal processing. METHOD: In the present study, the dichotic digit test (DDT) was used for binaural hearing, and the gap in noise (GIN) test was used to evaluate temporal hearing processing. RESULTS: The average values of GIN differed significantly between children with a history of OME and normal controls (p < 0.001). The mean values of the DDT score were significantly different between the two groups (p = 0.002). PMID- 26881325 TI - Boundary problem in Simon's two-stage clinical trial designs. AB - The activity of a new treatment in clinical trials with binary endpoints can be assessed by comparing the observed response rate to the target response rate. Traditionally, a one-sided hypothesis is used to make statistical inference, and the actual Type I error rate has to be computed over the parameter space of the null hypothesis. The monotonicity property is a fundamental property that guarantees the actual Type I error rate occurring at the boundary. One-arm two stage designs are considered in this article. We theoretically proved this important property when the final threshold value of a design is less than the first-stage sample size together with another weak condition being satisfied. The method used in this article may finally lead to the final complete proof of this property in the future. We also numerically proved that the monotonicity property is satisfied for designs with the first-stage and the second-stage sample sizes from 10 to 100. PMID- 26881326 TI - VATER/VACTERL Association and Caudal Regression with Xq25-q27.3 Microdeletion: A Case Report. AB - We report a term female neonate with vertebral anomalies, anal and urethral atresia, esophageal atresia with tracheoesophageal fistula (TEF), renal agenesis, pulmonary hypoplasia, genital and sacral appendages, and a single umbilical artery. Genetic studies revealed a 20.91 Mb interstitial deletion of the long arm of X chromosome: Xq25-q27.3. This is a new case of VATER/VACTERL association with Xq25 microdeletion. PMID- 26881327 TI - Osteomyoplastic Transtibial Amputation: The Ertl Technique. AB - Amputation may be required for management of lower extremity trauma and medical conditions, such as neoplasm, infection, and vascular compromise. The Ertl technique, an osteomyoplastic procedure for transtibial amputation, can be used to create a highly functional residual limb. Creation of a tibiofibular bone bridge provides a stable, broad tibiofibular articulation that may be capable of some distal weight bearing. Several different modified techniques and fibular bridge fixation methods have been used; however, no current evidence exists regarding comparison of the different techniques. Additional research is needed to elucidate the optimal patient population, technique, and postoperative protocol for the Ertl osteomyoplastic transtibial amputation technique. PMID- 26881328 TI - The Global AIMs Nano set: A 31-plex SNaPshot assay of ancestry-informative SNPs. AB - A 31-plex SNaPshot assay, named 'Global AIMs Nano', has been developed by reassembling the most differentiated markers of the EUROFORGEN Global AIM-SNP set. The SNPs include three tri-allelic loci and were selected with the goal of maintaining a balanced differentiation of: Africans, Europeans, East Asians, Oceanians and Native Americans. The Global AIMs Nano SNP set provides higher divergence between each of the five continental population groups than previous small-scale AIM sets developed for forensic ancestry analysis with SNaPshot. Both of these characteristics minimise potential bias when estimating co-ancestry proportions in individuals with admixed ancestry; more likely to be observed when using markers disproportionately informative for only certain population group comparisons. The optimised multiplex is designed to be easily implemented using standard capillary electrophoresis regimes and has been used to successfully genotype challenging forensic samples from highly degraded material with low level DNA. The ancestry predictive performance of the Global AIMs Nano set has been evaluated by the analysis of samples previously characterised with larger AIM sets. PMID- 26881329 TI - SkydancerPlex: A novel STR multiplex validated for forensic use in the hen harrier (Circus cyaneus). AB - The hen harrier (Circus cyaneus) is a bird of prey which is heavily persecuted in the UK because it preys on the game bird red grouse (Lagopus lagopus scoticus). To help investigations into illegal killings of hen harrier, a STR multiplex kit containing eight short tandem repeat (STR) markers and a chromohelicase DNA binding protein 1 (CHD 1) sexing marker was developed. The multiplex kit was tested for species specificity, sensitivity, robustness, precision, accuracy and stability. Full profiles were obtained with as little as 0.25 ng of template DNA. Concurrent development of an allelic ladder to ensure reliable and accurate allele designation across laboratories makes the SkydancerPlex the first forensic DNA profiling system in a species of wildlife to be fully validated according to SWGDAM and ISFG recommendations. An average profile frequency of 3.67 * 10(-8), a PID estimate of 5.3 * 10(-9) and a PID-SIB estimate of 9.7 * 10(-4) make the SkydancerPlex an extremely powerful kit for individualisation. PMID- 26881330 TI - Utilization of maternal health care services among indigenous women in Bangladesh: A study on the Mru tribe. AB - Despite startling developments in maternal health care services, use of these services has been disproportionately distributed among different minority groups in Bangladesh. This study aimed to explore the factors associated with the use of these services among the Mru indigenous women in Bangladesh. A total of 374 currently married Mru women were interviewed using convenience sampling from three administrative sub-districts of the Bandarban district from June to August of 2009. Associations were assessed using Chi-square tests, and a binary logistic regression model was employed to explore factors associated with the use of maternal health care services. Among the women surveyed, 30% had ever visited maternal health care services in the Mru community, a very low proportion compared with mainstream society. Multivariable logistic regression analyses revealed that place of residence, religion, school attendance, place of service provided, distance to the service center, and exposure to mass media were factors significantly associated with the use of maternal health care services among Mru women. Considering indigenous socio-cultural beliefs and practices, comprehensive community-based outreach health programs are recommended in the community with a special emphasis on awareness through maternal health education and training packages for the Mru adolescents. PMID- 26881331 TI - Clinical Approach to the Heavy Cannabis User in the Age of Medical Marijuana. AB - This article begins with a case vignette exemplifying the common clinical problem of heavy marijuana users. The epidemiology and basic science underlying cannabis dependence is outlined, followed by clinical strategies for basing a therapeutic alliance on known research findings and using motivational interviewing to deal with typical patterns of denial. PMID- 26881332 TI - Etirinotecan pegol for the treatment of breast cancer. AB - INTRODUCTION: Advanced breast cancer is incurable for most patients with limited therapeutic options. As such, there is a critical need for new and novel agents that lack cross-resistance and mitigate overlapping toxicities. AREAS COVERED: This review examines etirinotecan pegol as a promising new agent for the treatment of refractory metastatic breast cancer. Etirinotecan pegol is the first topoisomerase I inhibitor with a novel design: a long-acting polymer conjugate of irinotecan molecularly engineered to concentrate in vascularized tumors and provide sustained circulation time of SN38 for prolonged tumor cell exposure. Etirinotecan pegol pharmacology is reviewed in this paper along with safety and efficacy data from preclinical and clinical trials. In the phase II advanced breast cancer setting, etirinotecan pegol provided promising activity, which was maintained in poor prognostic subgroups, with low rates of neutropenia and neuropathy - issues plaguing our currently available agents. EXPERT OPINION: Etirinotecan pegol demonstrates anti-tumor activity and improved tolerability in patients with refractory metastatic breast cancer. As a novel topoisomerase I inhibitor in breast cancer, etirinotecan pegol holds great therapeutic potential, allowing the challenge of resistance in the advanced disease setting to be addressed. PMID- 26881333 TI - Post-treatment mechanical refining as a method to improve overall sugar recovery of steam pretreated hybrid poplar. AB - This study investigates the effect of mechanical refining to improve the sugar yield from biomass processed under a wide range of steam pretreatment conditions. Hybrid poplar chips were steam pretreated using six different conditions with or without SO2. The resulting water insoluble fractions were subjected to mechanical refining. After refining, poplar pretreated at 205 degrees C for 10min without SO2 obtained a 32% improvement in enzymatic hydrolysis and achieved similar overall monomeric sugar recovery (539kg/tonne) to samples pretreated with SO2. Refining did not improve hydrolyzability of samples pretreated at more severe conditions, nor did it improve the overall sugar recovery. By maximizing overall sugar recovery, refining could partially decouple the pretreatment from other unit operations, and enable the use of low temperature, non-sulfur pretreatment conditions. The study demonstrates the possibility of using post-treatment refining to accommodate potential pretreatment process upsets without sacrificing sugar yields. PMID- 26881334 TI - Co-production of bio-oil and propylene through the hydrothermal liquefaction of polyhydroxybutyrate producing cyanobacteria. AB - A polyhydroxybutyrate (PHB) producing cyanobacteria was converted through hydrothermal liquefaction (HTL) into propylene and a bio-oil suitable for advanced biofuel production. HTL of model compounds demonstrated that in contrast to proteins and carbohydrates, no synergistic effects were detected when converting PHB in the presence of algae. Subsequently, Synechocystis cf. salina, which had accumulated 7.5wt% PHB was converted via HTL (15% dry weight loading, 340 degrees C). The reaction gave an overall propylene yield of 2.6%, higher than that obtained from the model compounds, in addition to a bio-oil with a low nitrogen content of 4.6%. No propylene was recovered from the alternative non-PHB producing cyanobacterial strains screened, suggesting that PHB is the source of propylene. PHB producing microorganisms could therefore be used as a feedstock for a biorefinery to produce polypropylene and advanced biofuels, with the level of propylene being proportional to the accumulated amount of PHB. PMID- 26881335 TI - Enzyme feeding strategies for better fed-batch enzymatic hydrolysis of empty fruit bunch. AB - Lignin inhibitory becomes a major obstacle for enzymatic hydrolysis of empty fruit bunch conducted in high solid loading. Since current technology required high enzyme loading, surfactant application could not effectively used since it is only efficient in low enzyme loading. In addition, it will increase final operation cost. Hence, another method namely "proportional enzyme feeding" was investigated in this paper. In this method, enzyme was added to reactor proportionally to substrate addition, different from conventional method ("whole enzyme feeding") where whole enzyme was added prior to hydrolysis process started. Proportional enzyme feeding could increase enzymatic digestibility and glucose concentration up to 26% and 12% respectively, compared to whole enzyme feeding for hydrolysis duration more than 40h. If enzymatic hydrolysis was run less than 40h (25% solid loading), whole enzyme feeding is preferable. PMID- 26881337 TI - Evidence for electrohydrodynamic convection as a source of spontaneous self ordering in porous anodic alumina films. AB - A comparative study of self-ordering behaviour of anodic alumina films fabricated in a series of diluted (down to 0.05 M) oxalic acid electrolytes allowed developing a relationship between the supporting electrolyte concentration and self-ordering voltages for the formation of porous oxide materials. Besides its practical importance, this work elucidates some fundamental principles of porous alumina formation, e.g. it suggests that the cell patterning arises from the electrohydrodynamic (EHD) convection process rather than the interfacial tension gradients near the anode surface (Marangoni-type instability). PMID- 26881336 TI - Persistent organic pollutants in juvenile Magellanic Penguins (Spheniscus magellanicus) in South America. AB - Magellanic penguins, Spheniscus magellanicus, are the most abundant penguins living in temperate regions of South America and are good indicators of environmental pollution in the region. Persistent organic pollutants (POPs) were detected in the liver of Magellanic penguins found debilitated or dead on the beaches of Brazil (states of Rio de Janeiro, Sao Paulo, Santa Catarina and Rio Grande do Sul) between 2008 and 2012 as well as in Uruguay and Chile in 2011. Polychlorinated biphenyls (PCBs) were more prevalent than organochlorine pesticides (DDTs ~ HCB ~ Drins) and polybrominated diphenyl ethers (PBDEs). Among PCBs, penta-, hexa- and hepta-chlorinated congeners were predominant. Concentrations of POPs were similar between the Pacific and Atlantic penguin populations, except for PCBs, which were relatively higher in the Pacific population. During the study years (2008-2012), large variations were found in organochlorine pesticides and PCBs tended to decline. Overall, the southern portion of South America has low concentrations of POPs, with either a constant trend or evidence of decline. PMID- 26881338 TI - Long-Term Effects of Glucosamine and Chondroitin Sulfate on the Progression of Structural Changes in Knee Osteoarthritis: Six-Year Followup Data From the Osteoarthritis Initiative. AB - OBJECTIVE: To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA). METHODS: Participants were from the Osteoarthritis Initiative progression and incidence subcohorts, had magnetic resonance imaging (MRI) of the target knee at baseline and 6 years, joint space width >1 mm, and data available on Glu/CS consumption (n = 1,593). They were stratified into 2 main groups based on whether or not they had medial meniscal extrusion at baseline. The group with meniscal extrusion (n = 429) was further stratified into subgroups based on exposure or no exposure to Glu/CS as follows: not exposed, 1 year, 2-3 years, and 4-6 years. Cartilage volume was assessed using fully automated quantitative MRI technology. RESULTS: The Jonckheere-Terpstra trend test indicated that treatment with Glu/CS significantly reduced the cartilage volume loss in the global knee, associated with the lateral compartment. Multivariate analysis further demonstrated that the extent of the treatment's positive effect was related to exposure time to treatment, the protective effect at 6 years being significant in participants exposed to >=2 years of treatment. CONCLUSION: These findings provide future support for the long-term protective structure-modifying effects of Glu/CS treatment in knee OA subjects. PMID- 26881340 TI - Structures and photoelectric properties of five benzotrithiophene isomers-based donor-acceptor copolymers. AB - In this paper, we have investigated the structures, electronic and optical properties of five conjugated copolymers (BTT1-BTz, BTT2-BTz, BTT3-BTz, BTT4-BTz and BTT5-BTz) featuring benzotrithiophene (BTT) isomers as donor units and benzothiadiazole (BTz) as acceptor units, linked through thiophene spacers, employing many-body perturbation theory (MBPT). We have explored the isomer effects by configuration of the sulfur atoms in BTT units, aimed to get insight into how the structural modifications to the conjugated backbone can influence the molecular structures and electronic properties of conjugated polymers. Using the trimer as the computational model, the calculated low and high energy absorption bands (660 and 413 nm) for BTT1-BTz agree well with the experimental ones (645 and 430 nm) with a small offset of ~15 nm. On the basis of our calculations, it is found that the backbones of these polymers display different coplanarities, with the dihedral angles between the two neighboring rings varying from 12.3 degrees to 79.0 degrees . Importantly, both BTT1-BTz and BTT2-BTz exhibit intense adsorption around 660 and 623 nm, indicating their promising application in solar cells, whereas BTT3-BTz and BTT4-BTz display the intense adsorption at 569 and 551 nm, which are also usable in the tandem solar cells. BTT5-BTz has narrow and weak adsorption in the visible and infrared region, implying it is not conducive to the sunlight absorption. The blue shift of about 150 nm from BTT1-BTz to BTT5-BTz is suggested to be originated from the shorter effective conjugation lengths. PMID- 26881339 TI - The prevalence and predictors of bipolar and borderline personality disorders comorbidity: Systematic review and meta-analysis. AB - INTRODUCTION: Data about the prevalence of borderline personality (BPD) and bipolar (BD) disorders comorbidity are scarce and the boundaries remain controversial. We conducted a systematic review and meta-analysis investigating the prevalence of BPD in BD and BD in people with BPD. METHODS: Two independent authors searched MEDLINE, Embase, PsycINFO and the Cochrane Library from inception till November 4, 2015. Articles reporting the prevalence of BPD and BD were included. A random effects meta-analysis and meta-regression were conducted. RESULTS: Overall, 42 papers were included: 28 considering BPD in BD and 14 considering BD in BPD. The trim and fill adjusted analysis demonstrated the prevalence of BPD among 5273 people with BD (39.94 +/- 11.78 years, 44% males) was 21.6% (95% CI 17.0-27.1). Higher comorbid BPD in BD were noted in BD II participants (37.7%, 95% CI 21.9-56.6, studies=6) and North American studies (26.2%, 95% CI 18.7-35.3, studies=11). Meta regression established that a higher percentage of males and higher mean age significantly (p<0.05) predicted a lower prevalence of comorbid BPD in BD participants. The trim and fill adjusted prevalence of BD among 1814 people with BPD (32.22 +/- 7.35 years, 21.5% male) was 18.5% (95% CI 12.7-26.1). LIMITATIONS: Paucity of longitudinal/control group studies and accurate treatment records. CONCLUSIONS: BPD-BD comorbidity is common, with approximately one in five people experiencing a comorbid diagnosis. Based on current diagnostic constructs, and a critical interpretation of results, both qualitative and quantitative syntheses of the evidence prompt out the relevance of differences rather similarities between BD and BPD. PMID- 26881341 TI - [Determining freedom of choice in forensic psychiatry is of great importance to psychiatry as a whole]. PMID- 26881342 TI - [Psychopathology in families: an integral approach via the family outpatient clinic]. AB - BACKGROUND: Psychiatric disorders run in families. To bridge the gap between child and youth psychiatry and adult psychiatry, GGZ inGeest has started screening parents of new registered children for psychopathology - and if indicated - offers parents treatment in the same department as their children. AIM: To examine the feasibility and usefulness of this procedure, to investigate how many parents agree to screening, further diagnostics and treatment, and to find out how many parents have in fact suffered from recent psychiatric problems. METHOD: Prior to the children's first appointment, the parents were asked to complete a questionnaire, the Adult Self Report (ASR), about their own problems. If these scores were (sub)clinical, parents were invited to participate in a telephonic interview. This consisted of the Composite International Diagnostic Interview (CIDI) and Conners' Adult ADHD Rating Scales (CAARS). If the results indicate psychopathology, further psychiatric assessment and, if necessary, treatment is offered. RESULTS: The first response was 55.7% and, if indicated, most of the parents agreed on further diagnostics. On the ASR 2 out of 5 mothers (42.1%) and 1 out of 5 fathers (21.8%) reported problems that could point to a psychiatric disorder. According to the ASR, within this high-risk group 37% of the mothers met the criteria for an axis I diagnosis (less than one month earlier) compared to 70.6% of the fathers. A mood disorder was the primary diagnosis for women, whereas men most often suffered from an anxiety disorder. In total, 19.1% of the parents screened were suffering from recent psychopathology and 75% of this group agreed to receive mental health care (treatment at the family outpatient clinic or referred to another clinic). CONCLUSION: Implementation of the family outpatient clinic scheme is feasible. However, further efforts are needed in order to reach a larger group of parents, particularly fathers. The family outpatient clinic is useful because parents who suffer from psychopathology do not always receive mental health care. However, a randomised control trial is needed to determine whether parallel treatment of parents and children can improve the treatment outcome for children. PMID- 26881343 TI - [Risk factors and protective factors relating to suicide in the Netherlands and Flanders]. AB - BACKGROUND: The suicide rate is 82% higher in the Flanders region of Belgium than in the Netherlands. AIM: To investigate to what extent Flanders and the Netherlands differ with regard to the risk factors and protective factors relating to suicide and attempted suicide. METHOD: By means of a structured postal questionnaire, we collected data on the following topics from 2999 Flemish and Dutch people between 18 and 64 years: mental well-being and earlier attempts to commit suicide, the help they had received and their intention to seek help for psychological problems, awareness of the mental health care available, satisfaction with the help received, and attitudes to suicide. RESULTS: The incidence of psychological problems and suicidality did not differ significantly between Flanders and the Netherlands. Compared to Flemish people, Dutch people with psychological problems had received more psychological help and more often expressed the intention to seek help in the future. Furthermore, the Dutch were better informed about mental health care, and patient satisfaction was higher in the Netherlands. Compared to the Flemish people, the Dutch had more positive and understanding attitude to suicide. CONCLUSION: In general, risk factors for suicide were similar in the Netherlands and Flanders. However, the Dutch were characterised by more protective factors. We attempt to explain these differences and suggest ways of improving suicidal prevention policy. PMID- 26881344 TI - [Social dysfunction in schizotypy]. AB - BACKGROUND: Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. AIM: To describe schizotypy and its influence on social functioning. METHOD: We reviewed the literature systematically using the online databases PubMed and PsycINFO. RESULTS: The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. CONCLUSION: More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia. PMID- 26881345 TI - [Auditory verbal hallucinations in patients with borderline personality disorder]. AB - BACKGROUND: Traditionally, auditory verbal hallucinations (AVH) experienced by patients with a borderline personality disorder (BPD) are considered to be rare, to have a 'pseudo'-quality, and to cause little distress. AIM: To provide an overview of studies of the prevalence and phenomenological characteristics of AVHs in patients with a BPD, and of the ensuing degree of suffering. METHOD: We performed a systematic literature search using PubMed and the Ovid database. RESULTS: 27% of patients with a BPD experience AVH. Phenomenologically, these percepts are indistinguishable from those experienced by patients with a schizophrenia spectrum disorder. Hallucinations in several modalities were present in 50% of the patients with BPD. The mean time-span in which AVH were experienced was 17 years, the mean frequency was several minutes per day. The degree of suffering was high and the patient's life was interrupted to a moderate degree. CONCLUSION: AVH and other hallucinations are common in BPD. We advise clinicians to inquire directly whether patients experience them and to provide treatment whenever possible. However, one of the problems is, that evidence-based treatment methods such as antipsychotics, cognitive-behavioural therapy and transcranial magnetic stimulation have not yet been studied systematically for this specific patient group. PMID- 26881346 TI - [Hearing voices is an aspecific symptom]. PMID- 26881347 TI - [A personal diagnosis for patients who hear voices: symptoms can improve in a meaningful context]. AB - BACKGROUND: In his controversial book Beyond dsm-5 (written in Dutch) Jim van Os makes a plea for a 'personal diagnosis'. AIM: To describe how a personal diagnosis can be made in the case of patients who hear voices. METHOD: We described and tested extensively how we achieved a personal diagnosis for patients who hear voices. RESULTS: This method enabled us to establish a relationship between hearing voices and events in a patient's personal life. This association plays an important role in the patient's recovery. CONCLUSION: Such a personal diagnosis has important advantages, both for the patient who hear voices and for the professional: it is drawn up with the personal involvement of the patient, and strengthens the working relationship; the patient's personal history plays a central role. A personal diagnosis empowers the patient, it is written in language that the patient can understand. It also reveals possible ways of solving the patient's personal problems and can thereby lead to further treatment and recovery. PMID- 26881348 TI - [Could you please reduce your seclusion rates? To structure patient care by the methodical work approach]. AB - BACKGROUND: Creating a safe treatment environment with a minimum use of seclusion at a ward for intensive psychiatric care is a complex process involving many actors. Although s/he is accountable for the use of seclusion, the psychiatrist's influence on actual seclusion practices is limited. The methodical work approach (MWA) to patient care is designed to improve multidisciplinary care delivery. AIM: To investigate ways in which the psychiatrist can structure the treatment and reduce seclusion rates by introducing the MWA. METHOD: We performed a quantitative analysis of the effects that the implementation of the MWA on an intervention ward had on the use of seclusion, comparing the intervention ward to control wards. We also conducted a qualitative analysis of the changes that occurred in the work process and in the roles of the various professionals involved. RESULTS: The use of seclusion had reduced significantly more at the intervention ward than it had at the control wards. The reduced seclusion rates were associated with an increase in interdisciplinary collaboration and professionalisation. CONCLUSION: By helping to limit the use of seclusion, possibly due to enhanced interdisciplinary collaboration and professionalisation, the MWA offers new horizons for mental health care professionals and their patients. PMID- 26881349 TI - [A philosophical information leaflet to accompany a DSM classification]. AB - BACKGROUND: The introduction of the dsm-5 has re-ignited discussion about the classification of mental disorders. The public may have misconceptions with regard to the nature of the information contained in a dsm-classification. AIM: To bring about a conceptual switch so that the professional user of a classification sees it as an aid to diagnosis rather than as a definition of a problem or illness. METHOD: We devised a 'thought experiment' to serve as a support for dsm classifications. RESULTS: The 'thought experiment' led us to devise a medicine package containing a 'philosophical' information leaflet. This 'thought-experiment', the information leaflet and the medicine package were presented to both students and trainee doctors at the ucp in Groningen and to clinicians at the fpc dr. S. van Mesdag Clinic. CONCLUSION: Students and trainee doctors were able to make the desired conceptual switch as a result of 'the thought experiment' and with the help they received from the medicine packaging containing the 'philosophical' information leaflet. PMID- 26881350 TI - [Fatal aortarupture following electroconvulsive therapy]. AB - Electroconvulsive therapy (ect) is a highly effective and safe form of treatment in psychiatry. However, fatal cardiovascular complications are rarely discussed in the literature. We describe the case of a 49-year old man who died from a ruptured aorta following treatment with ect. PMID- 26881351 TI - [Are appearances deceptive? Evidence-based instead of marketing-based psychiatry]. PMID- 26881352 TI - [Interests in pharmacological research are wider than big pharma's interest in this field]. PMID- 26881356 TI - Waiting Room: Philip Evergood. PMID- 26881357 TI - Despite Potential Health Benefits of Maternity Leave, US Lags Behind Other Industrialized Countries. PMID- 26881358 TI - If You Can't Measure Performance, Can You Improve It? PMID- 26881365 TI - Integrating Predictive Analytics Into High-Value Care: The Dawn of Precision Delivery. PMID- 26881366 TI - A PIECE OF MY MIND. The Unreasonable Patient. PMID- 26881367 TI - Ensuring the Quality of Quality Metrics for Emergency Care. PMID- 26881368 TI - Embrace the Complexity: The US Preventive Services Task Force Recommendation on Screening for Autism Spectrum Disorder. PMID- 26881369 TI - In-Hospital Outcomes and Costs Among Patients Hospitalized During a Return Visit to the Emergency Department. AB - IMPORTANCE: Unscheduled short-term return visits to the emergency department (ED) are increasingly monitored as a hospital performance measure and have been proposed as a measure of the quality of emergency care. OBJECTIVE: To examine in hospital clinical outcomes and resource use among patients who are hospitalized during an unscheduled return visit to the ED. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of adult ED visits to acute care hospitals in Florida and New York in 2013 using data from the Healthcare Cost and Utilization Project. Patients with index ED visits were identified and followed up for return visits to the ED within 7, 14, and 30 days. EXPOSURES: Hospital admission occurring during an initial visit to the ED vs during a return visit to the ED. MAIN OUTCOMES AND MEASURES: In-hospital mortality, intensive care unit (ICU) admission, length of stay, and inpatient costs. RESULTS: Among the 9,036,483 index ED visits to 424 hospitals in the study sample, 1,758,359 patients were admitted to the hospital during the index ED visit. Of these patients, 149,214 (8.5%) had a return visit to the ED within 7 days of the index ED visit, 228,370 (13.0%) within 14 days, and 349,335 (19.9%) within 30 days, and 76,151 (51.0%), 122,040 (53.4%), and 190,768 (54.6%), respectively, were readmitted to the hospital. Among the 7,278,124 patients who were discharged during the index ED visit, 598,404 (8.2%) had a return visit to the ED within 7 days, 839,386 (11.5%) within 14 days, and 1,205,865 (16.6%) within 30 days. Of these patients, 86,012 (14.4%) were admitted to the hospital within 7 days, 121,587 (14.5%) within 14 days, and 173,279 (14.4%) within 30 days. The 86,012 patients discharged from the ED and admitted to the hospital during a return ED visit within 7 days had significantly lower rates of in-hospital mortality (1.85%) compared with the 1,609,145 patients who were admitted during the index ED visit without a return ED visit (2.48%) (odds ratio, 0.73 [95% CI, 0.69-0.78]), lower rates of ICU admission (23.3% vs 29.0%, respectively; odds ratio, 0.73 [95% CI, 0.71-0.76]), lower mean costs ($10,169 vs $10,799; difference, $629 [95% CI, $479-$781]), and longer lengths of stay (5.16 days vs 4.97 days; IRR, 1.04 [95% CI, 1.03-1.05]). Similar outcomes were observed for patients returning to the ED within 14 and 30 days of the index ED visit. In contrast, patients who returned to the ED after hospital discharge and were readmitted had higher rates of in-hospital mortality and ICU admission, longer lengths of stay, and higher costs during the repeat hospital admission compared with those admitted to the hospital during the index ED visit without a return ED visit. CONCLUSIONS AND RELEVANCE: Compared with adult patients who were hospitalized during the index ED visit and did not have a return visit to the ED, patients who were initially discharged during an ED visit and admitted during a return visit to the ED had lower in-hospital mortality, ICU admission rates, and in-hospital costs and longer lengths of stay. These findings suggest that hospital admissions associated with return visits to the ED may not adequately capture deficits in the quality of care delivered during an ED visit. PMID- 26881371 TI - Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population. AB - IMPORTANCE: Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. OBJECTIVE: To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. DESIGN, SETTING, AND PARTICIPANTS: Multisite, prospective, within individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. EXPOSURES: All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. MAIN OUTCOMES AND MEASURES: Number and proportion with acute HIV infections detected. RESULTS: Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%). CONCLUSIONS AND RELEVANCE: In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention. PMID- 26881373 TI - Screening for Prediabetes and Type 2 Diabetes Mellitus. PMID- 26881372 TI - Screening for Autism Spectrum Disorder in Young Children: US Preventive Services Task Force Recommendation Statement. AB - DESCRIPTION: New US Preventive Services Task Force (USPSTF) recommendation on screening for autism spectrum disorder (ASD) in young children. METHODS: The USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of brief, formal screening instruments for ASD administered during routine primary care visits and the benefits and potential harms of early behavioral treatment for young children identified with ASD through screening. POPULATION: This recommendation applies to children aged 18 to 30 months who have not been diagnosed with ASD or developmental delay and for whom no concerns of ASD have been raised by parents, other caregivers, or health care professionals. RECOMMENDATION: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for ASD in young children for whom no concerns of ASD have been raised by their parents or a clinician. (I statement). PMID- 26881370 TI - Association Between Interstitial Lung Abnormalities and All-Cause Mortality. AB - IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6 minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008 March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation. PMID- 26881374 TI - Hyperpigmented Reticulated Patch in an Older Man. PMID- 26881375 TI - Salt and Sodium Intake in China. PMID- 26881376 TI - US Trends for Diabetes Prevalence Among Adults. PMID- 26881377 TI - US Trends for Diabetes Prevalence Among Adults--Reply. PMID- 26881378 TI - Pharmacy Expenditures for Children With Serious Chronic Illness. PMID- 26881380 TI - Inaccurate Service Description. PMID- 26881379 TI - Pharmacy Expenditures for Children With Serious Chronic Illness--Reply. PMID- 26881382 TI - Error in Flow Diagram Randomization Boxes. PMID- 26881381 TI - Incorrect Minor Allele Frequency. PMID- 26881384 TI - Cancer of the Breast: Figures Which Show That Education Can Increase the Number of Cures. PMID- 26881385 TI - JAMA PATIENT PAGE. Screening for Autism Spectrum Disorder. PMID- 26881386 TI - Distinguishing the desire to learn from the desire to perform: The social value of achievement goals. AB - We sought to distinguish mastery goals (i.e., desire to learn) from performance goals (i.e., desire to achieve more positive evaluations than others) in the light of social judgment research. In a pilot study, we made a conceptual distinction between three types of traits (agency, competence, and effort) that are often undifferentiated. We then tested the relevance of this distinction for understanding how people pursuing either mastery or performance goals are judged. On self-perception, results revealed that effort was predicted by the adoption of mastery goals and agency by performance goals (Study 1). On judgments, results showed that (a) the target pursuing mastery goals was perceived as oriented toward effort, and (b) the target pursuing performance goals was oriented toward agency (Study 2). Finally, these links were shown again by participants who inferred a target's goals from his traits (Study 3). Results are discussed in terms of the social value of achievement goals at school. PMID- 26881387 TI - Association of Social Determinants With Children's Hospitals' Preventable Readmissions Performance. AB - IMPORTANCE: Performance-measure risk adjustment is of great interest to hospital stakeholders who face substantial financial penalties from readmissions pay-for performance (P4P) measures. Despite evidence of the association between social determinants of health (SDH) and individual patient readmission risk, the effect of risk adjusting for SDH on readmissions P4P penalties to hospitals is not well understood. OBJECTIVE: To determine whether risk adjustment for commonly available SDH measures affects the readmissions-based P4P penalty status of a national cohort of children's hospitals. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 43 free-standing children's hospitals within the Pediatric Health Information System database in the calendar year 2013. We evaluated hospital discharges from 2013 that met criteria for 3M Health Information Systems' potentially preventable readmissions measure for calendar year 2013. The analysis was conducted from July 2015 to August 2015. EXPOSURES: Two risk-adjustment models: a baseline model adjusted for severity of illness and an SDH-enhanced model that adjusted for severity of illness and the following 4 SDH variables: race, ethnicity, payer, and median household income for the patient's home zip code. MAIN OUTCOMES AND MEASURES: Change in a hospital's potentially preventable readmissions penalty status (ie, change in whether a hospital exceeded the penalty threshold) using an observed-to-expected potentially preventable readmissions ratio of 1.0 as a penalty threshold. RESULTS: For the 179,400 hospital discharges from the 43 hospitals meeting inclusion criteria, median (interquartile range [IQR]) hospital-level percentages for the SDH variables were 39.2% nonwhite (n = 71,300; IQR, 28.6%-54.6%), 17.9% Hispanic (n = 32,060; IQR, 6.7%-37.0%), and 58.7% publicly insured (n = 106,116; IQR, 50.4%-67.8%). The hospital median household income for the patient's home zip code was $ 40,674 (IQR, $ 35,912-$ 46,190). When compared with the baseline model, adjustment for SDH resulted in a change in penalty status for 3 hospitals within the 15-day window (2 were no longer above the penalty threshold and 1 was newly penalized) and 5 hospitals within the 30-day window (3 were no longer above the penalty threshold and 2 were newly penalized). CONCLUSIONS AND RELEVANCE: Risk adjustment for SDH changed hospitals' penalty status on a readmissions-based P4P measure. Without adjusting P4P measures for SDH, hospitals may receive penalties partially related to patient SDH factors beyond the quality of hospital care. PMID- 26881388 TI - Lipid desaturation - the next step in targeting lipogenesis in cancer? AB - Metabolic reprogramming is a central feature of transformed cells. Cancer metabolism is now fully back in the focus of cancer research, as the interactions between oncogenic signalling and cellular metabolic processes are uncovered. One aspect of metabolic reprogramming in cancer is alterations in lipid metabolism. In contrast to most untransformed tissues, which satisfy their demand from dietary lipids, cancer cells frequently re-activate de novo lipogenesis. However, compounds targeting fatty acid synthase (FASN), a multiprotein complex integral to lipogenesis, have so far shown limited efficacy in pre-clinical cancer models and to date only one FASN inhibitor has entered clinical trials. Recently, a number of studies have suggested that enhanced production of fatty acids in cancer cells could also increases their dependence on the activity of desaturases, a class of enzymes that insert double bonds into acyl-CoA chains. Targeting desaturase activity could provide a window of opportunity to selectively interfere with the metabolic activity of cancer cells. This review will summarise some key findings that implicate altered lipid metabolism in cancer and investigate the molecular interactions between lipid desaturation and cancer cell survival. PMID- 26881391 TI - Emerging ferroelectric transistors with nanoscale channel materials: the possibilities, the limitations. AB - Combining the nonvolatile, locally switchable polarization field of a ferroelectric thin film with a nanoscale electronic material in a field effect transistor structure offers the opportunity to examine and control a rich variety of mesoscopic phenomena and interface coupling. It is also possible to introduce new phases and functionalities into these hybrid systems through rational design. This paper reviews two rapidly progressing branches in the field of ferroelectric transistors, which employ two distinct classes of nanoscale electronic materials as the conducting channel, the two-dimensional (2D) electron gas graphene and the strongly correlated transition metal oxide thin films. The topics covered include the basic device physics, novel phenomena emerging in the hybrid systems, critical mechanisms that control the magnitude and stability of the field effect modulation and the mobility of the channel material, potential device applications, and the performance limitations of these devices due to the complex interface interactions and challenges in achieving controlled materials properties. Possible future directions for this field are also outlined, including local ferroelectric gate control via nanoscale domain patterning and incorporating other emergent materials in this device concept, such as the simple binary ferroelectrics, layered 2D transition metal dichalcogenides, and the 4d and 5d heavy metal compounds with strong spin-orbit coupling. PMID- 26881392 TI - Targeting the programmed cell death-1 pathway in breast and ovarian cancer. AB - PURPOSE OF REVIEW: Immune checkpoint blockade is changing cancer therapy. Targeting the programmed cell death-1 (PD-1) pathway releases T cells from inhibitory signals within the tumor microenvironment, thereby activating a latent antitumor immune response. Here, we review the biology underlying the activity of PD-1/programmed cell death-ligand 1 (PD-L1) antagonists, and data describing their clinical activity in breast and ovarian cancer. RECENT FINDINGS: Several antagonists of PD-1 and PD-L1 have been tested in breast and ovarian cancer. These drugs are generally well tolerated, with some immune-related adverse events that are typically easily managed. Objective response rates generally range from about 10 to 20% in both breast cancer and ovarian cancer, with durable responses noted in multiple trials. Selecting patients with PD-L1 expression by cells within the tumor microenvironment appears to enrich for responses. These agents are under accelerated development based on these promising early data. SUMMARY: Monoclonal antibody-based blockade of the PD-1 pathway results in objective and durable clinical responses in a subset of patients with breast or ovarian cancers, particularly those with PD-L1-positive cells within the tumor microenvironment. Current priorities are to refine biomarkers of therapeutic response, and to develop combination immunotherapy strategies that integrate PD 1/PD-L1 antagonists with both standard and immune-based cancer therapies to increase efficacy. PMID- 26881390 TI - A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population. AB - Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer. PMID- 26881393 TI - Diet-Induced Arthritis in Pigs: Comment on the Article by Scher et al. PMID- 26881394 TI - Realities of Anesthesia Care in Resource-limited Settings. PMID- 26881396 TI - A "Nitrous Oxide Gas" Advertising Bookmark from Dr. A. K. Harroun. PMID- 26881395 TI - Providing Anesthesia Care in Resource-limited Settings: A 6-year Analysis of Anesthesia Services Provided at Medecins Sans Frontieres Facilities. AB - BACKGROUND: Anesthesia is integral to improving surgical care in low-resource settings. Anesthesia providers who work in these areas should be familiar with the particularities associated with providing care in these settings, including the types and outcomes of commonly performed anesthetic procedures. METHODS: The authors conducted a retrospective analysis of anesthetic procedures performed at Medecins Sans Frontieres facilities from July 2008 to June 2014. The authors collected data on patient demographics, procedural characteristics, and patient outcome. The factors associated with perioperative mortality were analyzed. RESULTS: Over the 6-yr period, 75,536 anesthetics were provided to adult patients. The most common anesthesia techniques were spinal anesthesia (45.56%) and general anesthesia without intubation (33.85%). Overall perioperative mortality was 0.25%. Emergent procedures (0.41%; adjusted odds ratio [AOR], 15.86; 95% CI, 2.14 to 115.58), specialized surgeries (2.74%; AOR, 3.82; 95% CI, 1.27 to 11.47), and surgical duration more than 6 h (9.76%; AOR, 4.02; 95% CI, 1.09 to 14.88) were associated with higher odds of mortality than elective surgeries, minor surgeries, and surgical duration less than 1 h, respectively. Compared with general anesthesia with intubation, spinal anesthesia, regional anesthesia, and general anesthesia without intubation were associated with lower perioperative mortality rates of 0.04% (AOR, 0.10; 95% CI, 0.05 to 0.18), 0.06% (AOR, 0.26; 95% CI, 0.08 to 0.92), and 0.14% (AOR, 0.29; 95% CI, 0.18 to 0.45), respectively. CONCLUSIONS: A wide range of anesthetics can be carried out safely in resource-limited settings. Providers need to be aware of the potential risks and the outcomes associated with anesthesia administration in these settings. PMID- 26881397 TI - Porter's Pain King: Ether in Alcohol "for Man and Beast". PMID- 26881398 TI - Legacies of Charles Bernard Pittinger, M.D., M.S., F.A.C.A., D.A.B.A. (1913 1990). PMID- 26881399 TI - Conclusions on Ventilator-induced Mechanical Injuries Associated with Ventilation Using Abnormally Large Tidal Volume. PMID- 26881400 TI - In Reply. PMID- 26881403 TI - Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery: Erratum. PMID- 26881410 TI - Anesthesiologists Without Borders: Working for Better Surgical Outcomes in Resource Limited Settings. PMID- 26881411 TI - Initiation of robot-assisted radical prostatectomies in Finland: Impact on centralization and quality of care. AB - Objective The aim of this study was to analyze the impact of introduction of robot-assisted prostate surgery and its quality measures in Finland from 2008 to 2012. Materials and methods Registry data were collected for time trends and national distribution of prostate cancer surgery in Finland, while preoperative, operative and follow-up data were collected for quality measures. Results The number and proportion of robot-assisted laparoscopic radical prostatectomies (RALPs) increased rapidly and they accounted for 68% of all radical prostatectomies in 2012. The number of centers performing prostatectomies diminished from 25 to 20 at the expense of low-volume centers. In total, 1996 patients were operated on in the four RALP centers in 2008-2012. As anticipated, the learning curve was uniform between the centers, as were mean blood loss (212 ml), hospitalization (1.8 days) and catheterization times (10.6 days). At 3 and 12 months, 49.4% and 71.2% of patients, respectively, were totally continent (no pads). After unilateral nerve-sparing surgery, 9.9% and 5.1% had partial or normal erection at 3 months postoperatively and 14.8% and 20.4% at 12 months, respectively. If bilateral nerve sparing was done, the figures were 13.0% and 13.5% at 3 months and 14.6% and 34.9% at 12 months. Clavien-Dindo grade 3, 4 or 5 complications were seen in 0.3%, 0.3% and 0.1% of patients, respectively. Limitations of the study include non-standardized collection of outcome parameters. Conclusions This report shows that the main impact of adoption of RALP on a national level was rapid spontaneous centralization of prostate cancer surgery. The main advantages of minimally invasive prostatectomy, i.e. low blood loss and short hospitalization, are easily achieved, while continuous effort is necessary for improvements in surgical outcomes. PMID- 26881412 TI - Quality of Reporting Nutritional Randomized Controlled Trials in Patients With Cystic Fibrosis. AB - OBJECTIVE: Randomized controlled trials (RCTs) have a major role in the making of evidence-based guidelines. The aim of the present study was to critically appraise the RCTs that addressed nutritional interventions in patients with cystic fibrosis. METHODS: Embase, PubMed, and the Cochrane Library were systematically searched until July 2015. Methodology and reporting of nutritional RCTs were evaluated by the Consolidated Standards of Reporting Trials (CONSORT) checklist and additional dimensions relevant to patients with CF. RESULTS: Fifty one RCTs were included. Full details on methods were provided in a minority of studies. The mean duration of intervention was <6 months. 56.9% of the RCTs did not define a primary outcome; 70.6% of studies did not provide details on sample size calculation; and only 31.4% reported on the subgroup or separated between important subgroups. CONCLUSIONS: The examined RCTs were characterized by a weak methodology, a small number of patients with no sample size calculations, a relatively short intervention, and many times did not examine the outcomes that are important to the patient. Improvement over the years has been minor. PMID- 26881413 TI - Herpesvirus Infections and Transglutaminase Type 2 Antibody Positivity in Childhood: The Generation R Study. AB - OBJECTIVES: Persistent viral infections have been implicated in the etiology of autoimmune diseases in adulthood, but it is not known whether herpesviruses are associated with the development of celiac disease autoimmunity in childhood. We assessed whether herpesvirus infections are associated with transglutaminase type 2 antibody (TG2A) concentrations in children at 6 years of age. METHODS: The present study was embedded within a population-based prospective cohort study. Serum immunoglobulin G levels against Epstein-Barr virus, cytomegalovirus (CMV), and herpes simplex virus type 1 were measured by enzyme-linked immunosorbent assay , and TG2A concentrations with fluorescence enzyme immunoassay in 4420 children at 6 years of age. Children were categorized based on TG2A concentrations into negative (<7 U/mL), positive (>=7-70 U/mL), and strongly positive (>=70 U/mL), that is, 10 times upper limit normal. RESULTS: Fifty-nine children (1.3%) were TG2A positive, and of these 31 (53%) had concentrations 70 U/mL or more. Children with TG2A concentrations 70 U/mL or more were less often infected with CMV (adjusted odds ratio (aOR) 0.38, 95% CI 0.14-0.98, P = 0.04) and with any of the 3 viruses (aOR 0.38, 95% CI 0.18-0.78, P < 0.01) than children with TG2A negative concentrations. In addition, children with TG2A concentrations 70 U/mL or more were less often infected with 2 or more viruses than children with TG2A negative concentrations (aOR 0.15, 95% CI 0.03-0.65, P = 0.01). CONCLUSIONS: Both CMV single infection and combined CMV, Epstein-Barr virus and/or herpes simplex virus type 1 infections are inversely associated with strongly TG2A positivity. This may indicate a protective effect of herpesvirus infections in the pathogenesis of celiac disease autoimmunity. PMID- 26881414 TI - Synthesis and Utilization of Trialkylammonium-Substituted Cyclodextrins as Water Soluble Chiral NMR Solvating Agents for Anionic Compounds. AB - Cationic trialkylammonium-substituted alpha-, beta-, and gamma-cyclodextrins containing trimethyl-, triethyl-, and tri-n-propylammonium substituent groups were synthesized and analyzed for utility as water-soluble chiral nuclear magnetic resonance (NMR) solvating agents. Racemic and enantiomerically pure (3 chloro-2-hydroxypropyl)trimethyl-, triethyl-, and tri-n-propyl ammonium chloride were synthesized from the corresponding trialkyl amine hydrochloride and either racemic or enantiomerically pure epichlorohydrin. The ammonium salts were then reacted with alpha-, beta-, and gamma-cyclodextrins at basic pH to provide the corresponding randomly substituted cationic cyclodextrins. The (1) H NMR spectra of a range of anionic, aromatic compounds was recorded with the cationic cyclodextrins. Cyclodextrins with a single stereochemistry at the hydroxy group on the (2-hydroxypropyl)trialkylammonium chloride substituent were often but not always more effective than the corresponding cyclodextrin in which the C-2 position was racemic. In several cases, the larger triethyl or tri-n-propyl derivatives were more effective than the corresponding trimethyl derivative at causing enantiomeric differentiation. None of the cyclodextrin derivatives were consistently the most effective for all of the anionic compounds studied. PMID- 26881415 TI - Fluorescent supramolecular micelles for imaging-guided cancer therapy. AB - A novel smart fluorescent drug delivery system composed of a perylene diimide (PDI) core and block copolymer poly(d,l-lactide)-b-poly(ethyl ethylene phosphate) is developed and named as PDI-star-(PLA-b-PEEP)8. The biodegradable PDI-star-(PLA b-PEEP)8 is a unimolecular micelle and can self-assemble into supramolecular micelles, called as fluorescent supramolecular micelles (FSMs), in aqueous media. An insoluble drug camptothecin (CPT) can be effectively loaded into the FSMs and exhibits pH-responsive release. Moreover, the FSMs with good biocompatibility can also be employed as a remarkable fluorescent probe for cell labelling because the maximum emission of PDI is beneficial for bio-imaging. The flow cytometry and confocal laser scanning microscopy analysis demonstrate that the micelles are easily endocytosed by cancer cells. In vitro and in vivo tumor growth-inhibitory studies reveal a better therapeutic effect of FSMs after CPT encapsulation when compared with the free CPT drug. The multifunctional FSM nanomedicine platform as a nanovehicle has great potential for fluorescence imaging-guided cancer therapy. PMID- 26881416 TI - Comparative adoption of cone beam computed tomography and panoramic radiography machines across Australia. AB - BACKGROUND: The aim of the present study was to assess the current adoption of cone beam computed tomography (CBCT) and panoramic radiography (PR) machines across Australia. METHODS: Information regarding registered CBCT and PR machines was obtained from radiation regulators across Australia. The number of X-ray machines was correlated with the population size, the number of dentists, and the gross state product (GSP) per capita, to determine the best fitting regression model(s). RESULTS: In 2014, there were 232 CBCT and 1681 PR machines registered in Australia. Based on absolute counts, Queensland had the largest number of CBCT and PR machines whereas the Northern Territory had the smallest number. However, when based on accessibility in terms of the population size and the number of dentists, the Australian Capital Territory had the most CBCT machines and Western Australia had the most PR machines. The number of X-ray machines correlated strongly with both the population size and the number of dentists, but not with the GSP per capita. CONCLUSIONS: In 2014, the ratio of PR to CBCT machines was approximately 7:1. Projected increases in either the population size or the number of dentists could positively impact on the adoption of PR and CBCT machines in Australia. PMID- 26881419 TI - In vivo evaluation of a simvastatin-loaded nanostructured lipid carrier for bone tissue regeneration. AB - Alveolar bone loss has long been a challenge in clinical dental implant therapy. Simvastatin (SV) has been demonstrated to exert excellent anabolic effects on bone. However, the successful use of SV to increase bone formation in vivo largely depends on the local concentration of SV at the site of action, and there have been continuing efforts to develop an appropriate delivery system. Specifically, nanostructured lipid carrier (NLC) systems have become a popular type of encapsulation carrier system. Therefore, SV-loaded NLCs (SNs) (179.4 nm in diameter) were fabricated in this study, and the osteogenic effect of the SNs was evaluated in a critical-sized rabbit calvarial defect. Our results revealed that the SNs significantly enhanced bone formation in vivo, as evaluated by hematoxylin and eosin (HE) staining, immunohistochemistry, and a fluorescence analysis. Thus, this novel nanostructured carrier system could be a potential encapsulation carrier system for SV in bone regeneration applications. PMID- 26881420 TI - Suniti Solomon, Founder-Director Y.R. Gaitonde Centre for AIDS Research and Education (YRG CARE). PMID- 26881417 TI - Framing Financial Incentives to Increase Physical Activity Among Overweight and Obese Adults: A Randomized, Controlled Trial. AB - BACKGROUND: Financial incentive designs to increase physical activity have not been well-examined. OBJECTIVE: To test the effectiveness of 3 methods to frame financial incentives to increase physical activity among overweight and obese adults. DESIGN: Randomized, controlled trial. (ClinicalTrials.gov: NCT 02030119). SETTING: University of Pennsylvania. PARTICIPANTS: 281 adult employees (body mass index >=27 kg/m2). INTERVENTION: 13-week intervention. Participants had a goal of 7000 steps per day and were randomly assigned to a control group with daily feedback or 1 of 3 financial incentive programs with daily feedback: a gain incentive ($1.40 given each day the goal was achieved), lottery incentive (daily eligibility [expected value approximately $1.40] if goal was achieved), or loss incentive ($42 allocated monthly upfront and $1.40 removed each day the goal was not achieved). Participants were followed for another 13 weeks with daily performance feedback but no incentives. MEASUREMENTS: Primary outcome was the mean proportion of participant-days that the 7000-step goal was achieved during the intervention. Secondary outcomes included the mean proportion of participant days achieving the goal during follow-up and the mean daily steps during intervention and follow-up. RESULTS: The mean proportion of participant-days achieving the goal was 0.30 (95% CI, 0.22 to 0.37) in the control group, 0.35 (CI, 0.28 to 0.42) in the gain-incentive group, 0.36 (CI, 0.29 to 0.43) in the lottery-incentive group, and 0.45 (CI, 0.38 to 0.52) in the loss-incentive group. In adjusted analyses, only the loss-incentive group had a significantly greater mean proportion of participant-days achieving the goal than control (adjusted difference, 0.16 [CI, 0.06 to 0.26]; P = 0.001), but the adjusted difference in mean daily steps was not significant (861 [CI, 24 to 1746]; P = 0.056). During follow-up, daily steps decreased for all incentive groups and were not different from control. LIMITATION: Single employer. CONCLUSION: Financial incentives framed as a loss were most effective for achieving physical activity goals. PRIMARY FUNDING SOURCE: National Institute on Aging. PMID- 26881418 TI - Spatiotemporal patterns of population in mainland China, 1990 to 2010. AB - According to UN forecasts, global population will increase to over 8 billion by 2025, with much of this anticipated population growth expected in urban areas. In China, the scale of urbanization has, and continues to be, unprecedented in terms of magnitude and rate of change. Since the late 1970s, the percentage of Chinese living in urban areas increased from ~18% to over 50%. To quantify these patterns spatially we use time-invariant or temporally-explicit data, including census data for 1990, 2000, and 2010 in an ensemble prediction model. Resulting multi temporal, gridded population datasets are unique in terms of granularity and extent, providing fine-scale (~100 m) patterns of population distribution for mainland China. For consistency purposes, the Tibet Autonomous Region, Taiwan, and the islands in the South China Sea were excluded. The statistical model and considerations for temporally comparable maps are described, along with the resulting datasets. Final, mainland China population maps for 1990, 2000, and 2010 are freely available as products from the WorldPop Project website and the WorldPop Dataverse Repository. PMID- 26881421 TI - Applying the Principles of McDonaldization to Medicine. PMID- 26881422 TI - Mathematical Method for Analysis of the Refractive Outcome after Toric Intraocular Lens Implantation. AB - PURPOSE: We aimed to develop a self-designed software programmed with a mathematical method that analyzes the refractive outcome after toric intraocular lens (IOL) implantation, taking the axis misalignment of the toric IOL into consideration. METHODS: A mathematical method that can analyze the refractive outcome after toric IOL implantation was devised. Compared with the conventional method, which performs the analysis based on precise alignment of the IOL, optional meridian orientations of the toric IOL were taken into account in this method. Self-designed computer software was developed using the mathematical method. RESULTS: Relatively high accordance was achieved between the mathematical analysis and the actual postoperative outcome. The mean predicted spherical power was 0.37 +/- 0.74 dpt, and the mean measured spherical power was 0.37 +/- 0.71 dpt (paired t test, p = 0.98). The mean predicted cylindrical power was -1.35 +/- 0.86 dpt, and the mean measured cylindrical power was -1.42 +/- 0.85 dpt (p = 0.27). The mean predicted change in the astigmatic axis was 33.7 +/- 11.8 degrees , and the mean measured parameter was 32.5 +/- 15.4 degrees (p = 0.49). CONCLUSIONS: The advantage of the present mathematical method is that the postoperative refractive outcome can be analyzed under IOL misalignment. PMID- 26881423 TI - Congenital Hypothyroidism: Long-Term Experience with Early and High Levothyroxine Dosage. AB - AIM: To assess the management and outcome of the congenital hypothyroidism (CH) patients followed at our institution since the introduction of systemic neonatal screening for CH. STUDY DESIGN: The records of 139 CH patients referred to our center between 1978 and 2014 were retrospectively reviewed. Biochemical and imaging data at diagnosis, initial treatment and growth were analyzed. RESULTS: 111 patients had thyroid dysgenesis (64 ectopy, 46 athyreosis and 1 hypoplasia) and 28 patients had a gland in situ (17 dyshormonogenesis/goiter and 11 normal sized gland). Levothyroxine treatment was initiated at a median age of 11 days with a mean dose of 11.4 ug/kg/day. Compared to those with ectopy, patients with athyreosis had higher thyroid-stimulating hormone (TSH) and lower thyroxine at diagnosis as well as more delayed bone maturation. Between 1978 and 2014, we observed earlier treatment and earlier TSH normalization. Birth auxology was slightly above the mean of the reference population. Growth at 1 and 6 years and school progression at 11 years were similar to those of the reference population. CONCLUSION: Ectopy is the commonest cause of CH. Children with CH treated early with a mean levothyroxine dose of 11.4 ug/kg/day had a median TSH of 3.07 mU/l at 1 month of age and normal growth. PMID- 26881425 TI - Psychology and health after apartheid: Or, Why there is no health psychology in South Africa. AB - As part of a growing literature on the histories of psychology in the Global South, this article outlines some historical developments in South African psychologists' engagement with the problem of "health." Alongside movements to formalize and professionalize a U.S.-style "health psychology" in the 1990s, there arose a parallel, eclectic, and more or less critical psychology that contested the meaning and determinants of health, transgressed disciplinary boundaries, and opposed the responsibilization of illness implicit in much health psychological theorizing and neoliberal discourse. This disciplinary bifurcation characterized South African work well into the postapartheid era, but ideological distinctions have receded in recent years under a new regime of knowledge production in thrall to the demands of the global market. The article outlines some of the historical-political roots of key trends in psychologists' work on health in South Africa, examining the conditions that have impinged on its directions and priorities. It raises questions about the future trajectories of psychological research on health after 20 years of democracy, and argues that there currently is no "health psychology" in South Africa, and that the discipline is the better for it. PMID- 26881424 TI - Release of Matrix Metalloproteinases-2 and 9 by S-Nitrosylated Caveolin-1 Contributes to Degradation of Extracellular Matrix in tPA-Treated Hypoxic Endothelial Cells. AB - Intracranial hemorrhage remains the most feared complication in tissue plasminogen activator (tPA) thrombolysis for ischemic stroke. However, the underlying molecular mechanisms are still poorly elucidated. In this study, we reported an important role of caveolin-1 (Cav-1) s-nitrosylation in matrix metalloproteinase (MMP)-2 and 9 secretion from tPA-treated ischemic endothelial cells. Brain vascular endothelial cells (bEND3) were exposed to oxygen-glucose deprivation (OGD) for 2 h before adding recombinant human tPA for 6 h. This treatment induced a significant increase of MMP2 and 9 in the media of bEND3 cells and a simultaneous degradation of fibronectin and laminin beta-1, the two main components of extracellular matrix (ECM). Inhibition of MMP2 and 9 with SB 3CT completely blocked the degradation of fibronectin and laminin beta-1. ODG+tPA treatment led to Cav-1 shedding from bEND3 cells into the media. Notably, OGD triggered nitric oxide (NO) production and S-nitrosylationof Cav-1 (SNCav-1). Meanwhile tPA induced activation of ERK signal pathway and stimulates the secretion of SNCav-1. Pretreatment of bEND3 cells with C-PTIO (a NO scavenger) or U0126 (a specific ERK inhibitor) significantly reduced OGD-induced S nitrosylation of Cav-1 in cells and blocked the secretion of Cav-1 and MMP2 and 9 into the media as well as the degradation of fibronectin and laminin beta-1 in OGD and tPA-treated cells. These data indicate that OGD-triggered Cav-1 S nitrosylation interacts with tPA-induced ERK activation to augment MMP2 and 9 secretion and subsequent ECM degradation, which may account for the exacerbation of ischemic blood brain barrier damage following tPA thrombolysis for ischemic stroke. PMID- 26881426 TI - When Children Become Adults: Should Biobanks Re-Contact? PMID- 26881427 TI - Survey of the Influence of the Width of Urban Branch Roads on the Meeting of Two Way Vehicle Flows. AB - Branch roads, which are densely distributed in cities, allow for the flow of local traffic and provide connections between the city and outlying areas. Branch roads are typically narrow, and two-way traffic flows on branch roads are thus affected when vehicles traveling in opposite directions meet. This study investigates the changes in the velocities of vehicles when they meet on two-way branch roads. Various widths of branch roads were selected, and their influence on traffic flows was investigated via a video survey. The results show that, depending on the average vehicle velocity, branch roads require different widths to prevent a large decrease in velocity when vehicles meet. When the velocity on a branch road is not high (e.g., the average velocity without meeting is approximately 6 m/s), appropriately increasing the road width will notably increase the meeting velocity. However, when the velocity is high (e.g., the average velocity without meeting is greater than 10 m/s), there is a large decrease in velocity when meeting even if the road surface is wide (6.5 m). This study provides a basis for selecting the width of urban branch roads and the simulation of bidirectional traffic on such roads. PMID- 26881428 TI - Preserving a Comprehensive Vegetation Knowledge Base--An Evaluation of Four Historical Soviet Vegetation Maps of the Western Pamirs (Tajikistan). AB - We edited, redrew, and evaluated four unpublished historical vegetation maps of the Western Pamirs (Tajikistan) by the Soviet geobotanist Okmir E. Agakhanjanz. These maps cover an area of 5,188 km2 and date from 1958 to 1960. The purpose of this article is to make the historic vegetation data available to the scientific community and thus preserve a hitherto non available and up to now neglected or forgotten data source with great potential for studies on vegetation and ecosystem response to global change. The original hand-drawn maps were scanned, georeferenced, and digitized and the corresponding land cover class was assigned to each polygon. The partly differing legends were harmonized and plant names updated. Furthermore, a digital elevation model and generalized additive models were used to calculate response curves of the land cover classes and to explore vegetation-topography relationships quantitatively. In total, 2,216 polygons belonging to 13 major land cover classes were included that are characterized by 252 different plant species. As such, the presented maps provide excellent comparison data for studies on vegetation and ecosystem change in an area that is deemed to be an important water tower in Central Asia. PMID- 26881430 TI - Pediatric Continuous Renal Replacement Therapy. AB - BACKGROUND: Continuous renal replacement therapy (CRRT) and peritoneal dialysis are the preferred forms of dialysis delivery in critically ill children for the treatment of severe acute kidney injury. The epidemiology and the outcome of acute pediatric dialysis will be reviewed. SUMMARY: The prospective pediatric CRRT (pCRRT) registry has provided important epidemiologic information: pCRRT is required in about 5% of patients in pediatric intensive care units, and the mortality rate of these patients is about 60%. CRRT outcomes are significantly associated with age, the presence of multiple organ dysfunction syndrome and the amount of fluid overload in children before CRRT inception. The timing and the dose of pCRRT are to be further evaluated in prospective trials. A final aspect worthy of review is a technical issue: the accuracy of new-generation CRRT monitors and novel dedicated circuits that have been developed. In future years, the delivery and the outcome of pCRRT are expected to significantly improve, with the target of expanding and anticipating dialysis initiation in critically ill pediatric patients. PMID- 26881429 TI - Disparities in Prevalence of Cardiometablic Risk Factors in Rural, Urban-Poor, and Urban-Middle Class Women in India. AB - OBJECTIVE: Urbanization is an important determinant of cardiovascular disease (CVD) risk. To determine location-based differences in CVD risk factors in India we performed studies among women in rural, urban-poor and urban middle-class locations. METHODS: Population-based cross-sectional studies in rural, urban poor, and urban-middle class women (35-70 y) were performed at multiple sites. We evaluated 6853 women (rural 2616, 5 sites; urban-poor 2008, 4 sites; urban middle class 2229, 11 sites) for socioeconomic, lifestyle, anthropometric and biochemical risk factors. Descriptive statistics are reported. RESULTS: Mean levels of body mass index (BMI), waist circumference, waist-hip ratio (WHR), systolic BP, fasting glucose and cholesterol in rural, urban-poor and urban middle class women showed significantly increasing trends (ANOVAtrend, p <0.001). Age-adjusted prevalence of diabetes and risk factors among rural, urban-poor and urban-middle class women, respectively was, diabetes (2.2, 9.3, 17.7%), overweight BMI >=25 kg/m2 (22.5, 45.6, 57.4%), waist >80 cm (28.3, 63.4, 61.9%), waist >90 cm (8.4, 31.4, 38.2%), waist hip ratio (WHR) >0.8 (60.4, 90.7, 88.5), WHR>0.9 (13.0, 44.3, 56.1%), hypertension (31.6, 48.2, 59.0%) and hypercholesterolemia (13.5, 27.7, 37.4%) (Mantel Haenszel X2 ptrend <0.01). Inverse trend was observed for tobacco use (41.6, 19.6, 9.4%). There was significant association of hypertension, hypercholesterolemia and diabetes with overweight and obesity (adjusted R2 0.89-0.99). CONCLUSIONS: There are significant location based differences in cardiometabolic risk factors in India. The urban-middle class women have the highest risk compared to urban-poor and rural. PMID- 26881432 TI - Microbial Community Profile and Water Quality in a Protected Area of the Caatinga Biome. AB - The Caatinga is a semi-arid biome in northeast Brazil. The Paraguacu River is located in the Caatinga biome, and part of its course is protected by the National Park of Chapada Diamantina (PNCD). In this study we evaluated the effect of PNCD protection on the water quality and microbial community diversity of this river by analyzing water samples obtained from points located inside and outside the PNCD in both wet and dry seasons. Results of water quality analysis showed higher levels of silicate, ammonia, particulate organic carbon, and nitrite in samples from the unprotected area compared with those from protected areas. Pyrosequencing of the 16S rRNA genes revealed that Burkholderiales was abundant in samples from all three sites during both seasons and was represented primarily by the genus Polynucleobacter and members of the Comamonadaceae family (e.g., genus Limnohabitans). During the dry season, the unprotected area showed a higher abundance of Flavobacterium sp. and Arthrobacter sp., which are frequently associated with the presence and/or degradation of arsenic and pesticide compounds. In addition, genes that appear to be related to agricultural impacts on the environment, as well as those involved in arsenic and cadmium resistance, copper homeostasis, and propanediol utilization, were detected in the unprotected areas by metagenomic sequencing. Although PNCD protection improves water quality, agricultural activities around the park may affect water quality within the park and may account for the presence of bacteria capable of pesticide degradation and assimilation, evidencing possible anthropogenic impacts on the Caatinga. PMID- 26881431 TI - Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-kappaB Pathway. AB - A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3 dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-kappaB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKalpha phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-kappaB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-kappaB pathway activates IDO1 expression in vivo. The addition of Tumor Necrosis Factor Associated Factors (TRAF) TRAF 2, 3 and TRAF6 blocking peptides to vaccine inoculated DCs was shown to inhibit IDO1 biosynthesis. This experimental outcome suggests vaccine activation of the TNFR super-family receptor pathway leads to upregulation of IDO1 biosynthesis in CTB-INS inoculated dendritic cells. Together, our experimental data suggest the CTB-INS vaccine uses a TNFR-dependent signaling pathway of the non-canonical NF-kappaB signaling pathway resulting in suppression of dendritic cell mediated type 1 diabetes autoimmunity. PMID- 26881433 TI - A Robust and Accurate Two-Step Auto-Labeling Conditional Iterative Closest Points (TACICP) Algorithm for Three-Dimensional Multi-Modal Carotid Image Registration. AB - Atherosclerosis is among the leading causes of death and disability. Combining information from multi-modal vascular images is an effective and efficient way to diagnose and monitor atherosclerosis, in which image registration is a key technique. In this paper a feature-based registration algorithm, Two-step Auto labeling Conditional Iterative Closed Points (TACICP) algorithm, is proposed to align three-dimensional carotid image datasets from ultrasound (US) and magnetic resonance (MR). Based on 2D segmented contours, a coarse-to-fine strategy is employed with two steps: rigid initialization step and non-rigid refinement step. Conditional Iterative Closest Points (CICP) algorithm is given in rigid initialization step to obtain the robust rigid transformation and label configurations. Then the labels and CICP algorithm with non-rigid thin-plate spline (TPS) transformation model is introduced to solve non-rigid carotid deformation between different body positions. The results demonstrate that proposed TACICP algorithm has achieved an average registration error of less than 0.2mm with no failure case, which is superior to the state-of-the-art feature based methods. PMID- 26881435 TI - Oxidative Stress in Polycystic Ovary Syndrome. AB - Backgrouund: Polycystic ovary syndrome is a multifaceted disorder with a pathogenetic pathway that is not fully understood yet. Apart from hormonal derangements, insulin signaling defects and adipose tissue dysfunction, oxidative stress, defined as an imbalance derived from excessive formation of oxidants in the presence of limited antioxidants defenses, has been actively implicated in the etiology of the syndrome. METHODS: This review focuses on understanding the putative role of oxidative stress in the pathophysiology of PCOS and analyzing its interconnection with the rest etiologic parameters and its contribution to the reproductive and metabolic manifestations of the syndrome. RESULTS: Although underlying mechanisms have not been fully elucidated yet, it becomes evident that oxidative stress holds a respectable share in the pathogenesis of PCOS. In fact, PCOS can be considered as a purely oxidative state, where the body antioxidants cannot outweigh the excessive production of free radicals. CONCLUSION: Oxidative stress, in conjunction with the rest etiologic mechanisms of PCOS and the cardinal contribution of environmental factors, leads to an adverse redox status that stigmatizes the natural process of the syndrome. PMID- 26881436 TI - Covalently and Ionically Crosslinked Chitosan Nanogels for Drug Delivery. AB - Chitosan nanogels present a very interesting combination of valuable characteristics for drug delivery; those derived from their nanometric size, such as, large surface area, rapid stimuli-response, and easy functionalization; and those emerged especially from their biocompatibility, biodegradability and mucoadhesive nature. Due to this, chitosan nanogels have reached a prominent position as nanocarriers and have originated accelerated research worldwide. Diverse methods to prepare chitosan nanogels have been reported, showing a dependence on final swelling, drug encapsulation capability and release properties with different synthesis variables, in such a way that they can be exploited to be modulated. The present review describes the properties of chitosan nanogels, along with the different methods of crosslinking and confining chitosan in nanosized particles, and the various fields of drug delivery where they have been applied. This work aims to emphasize the connection between the characteristics of chitosan and the synthetic variables with the final properties of chitosan nanogels in order to enhance controlled drug loading and a sustained release. PMID- 26881434 TI - CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. AB - Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent kinase, CDK1. This was discovered using parallel siRNA screens in KRAS mutant and wild type colorectal isogenic tumour cells and subsequently validated in a genetically diverse panel of 26 colorectal and pancreatic tumour cell models. This established that the KRAS/CDK1 synthetic lethality applies in tumour cells with either amino acid position 12 (p.G12V, pG12D, p.G12S) or amino acid position 13 (p.G13D) KRAS mutations and can also be replicated in vivo in a xenograft model using a small molecule CDK1 inhibitor. Mechanistically, CDK1 inhibition caused a reduction in the S-phase fraction of KRAS mutant cells, an effect also characterised by modulation of Rb, a master control of the G1/S checkpoint. Taken together, these observations suggest that the KRAS/CDK1 interaction is a robust synthetic lethal effect worthy of further investigation. PMID- 26881437 TI - Taste and Hypertension in Humans: Targeting Cardiovascular Disease. AB - The association between salty taste and NaCl intake with hypertension is well established, although it is far from completely understood. Other taste types such as sweet, umami or bitter have also been related to alterations in blood pressure. Here, we review the mutual relationship between taste and hypertension to identify potential avenues to better control blood pressure. This review focuses on published data involving humans, with the exception of a section on molecular mechanisms. There is compelling evidence to suggest that changes in salty taste sensitivity can be used to predict the onset of hypertension. This goes hand in hand with the medical concept of sodium sensitivity, which also increases with age, particularly in hypertensive patients. The association of hypertension with the loss of taste acuity less definitive with some data/conclusions masked by the use of anti-hypertensive drugs. In fact, this group of therapeutic agents can reduce food taste perception resulting in mild to severe hypogeusia and dysgeusia. In the elderly, antihypertensive drugs may lead to a loss of appetite, thus, selecting treatments with low or no impact on taste perception should be advised. Pharmacological approaches to mitigate cardiovascular disease (CVD) could well take a different spin in the future following the discovery of taste receptors (TAS1R and TAS2R) in the cardiovascular system. Finally, long-term dietary strategies to minimize the risk of development of hypertension and CVD are discussed identifying several nutrients and public health policies with relevant potential. PMID- 26881438 TI - Chemical Senses Affecting Cough and Swallowing. AB - BACKGROUND: Dysfunction of swallowing and coughing leads to life-threatening aspiration pneumonia, especially in the elderly. In order to induce the cough and swallowing reflexes efficiently, sensory inputs to trigger the reflexes are essential. METHODS: Both the cough and swallowing reflexes respond to mechanical and chemical stimuli. However, the mechanisms of action of the two reflexes are not homogeneous. Some substances stimulate both reflexes, but others stimulate one of the reflexes and inhibit the other one. RESULTS: Capsaicin, a TRPV1 agonist, stimulates both the cough and swallowing reflexes. Menthol, a TRPM8 agonist, stimulates the swallowing reflex, but it inhibits the cough reflex, especially if applied to the nose. Acid stimulates the cough reflex but its effect on the swallowing reflex is complicated. Theophylline inhibits the cough reflex by decreasing the excitability of sensory nerves, whereas it stimulates the swallowing reflex by antagonizing adenosine receptors. In smoking, cigarette smoke and nicotine have different effects. Cigarette smoke stimulates the cough reflex, while it inhibits the swallowing reflex. Nicotine inhibits the cough reflex but does not affect the swallowing reflex. CONCLUSION: Whenever you prescribe for an abnormality of one of the reflexes, you should think about the effect of the prescription on the other reflex. PMID- 26881439 TI - Chemical Sensing Regulates Mastication/Swallowing. AB - Mastication and swallowing are the first stage of digestion involving several motor processes such as food intake, intra-oral food transport, bolus formation and chewing and swallowing reflex. These complicated motor functions are accomplished by the well-coordinated activities in the jaw, hyoid, tongue, facial and pharyngeal muscles. Although the basic activity patterns of these movements are controlled by the brainstem pattern generators, these movements generate various peripheral sensory inputs. Among the sensory inputs, it is well-known that somatic sensory inputs play important roles in reflexively modulating the movements so that the final motor outputs fit the environmental demand. However, little is known about the effects of chemical sensory inputs such as taste and olfaction originating from the ingested foods by these movements. A possible reason could be raised that cognition of the chemical sensory inputs at the higher brain also influences the movements, so it is difficult to discuss the neural mechanisms underlying the observed effect. In this review, we focus on the effects of chemical sensory inputs on the masticatory movements and initiation of swallowing. We first summarize chemical sensory inputs occurring during mastication and swallowing, and their receptive mechanisms. In addition, we will introduce the effect of application of monosodium L-glutamate (MSG) solution as an umami taste to the oropharynx on the swallow initiation which is involuntary controlled and the possible neural mechanisms underlying this effect is discussed. PMID- 26881440 TI - Chemical Senses in Cancer Patients. AB - BACKGROUND: Cancer and its treatment therapies, such as chemotherapy and radiotherapy, have negative effects on taste and smell functions. It is easy to explain smell and taste dysfunctions when a cancer involves the peripheric end organs or neurologic pathways of smell and taste. However, it is difficult to understand how distortion in sensory perception develops as cancer progresses and cancer therapies are applied, because few studies on this subject have described heterogeneous oncological patient populations who are receiving different treatment regimens. METHODS: A literature review was performed about the chemical senses of the patients with various cancer types, and also about the possible mechanisms of taste and smell dysfunctions in cancer patients. RESULTS: Chemotherapy and radiotherapy may cause taste and smell alterations by destroying taste and olfactory receptor cells, creating alterations on the surfaces of cells and receptors as well as interrupting neural coding. The prevalence of taste dysfunctions in cancer patients has been reported to be up to 77%. Unlike taste dysfunction, diminished sensitivity of smell in cancer patients is described infrequently and the available literature contains some conflicting results for smell dysfunction in cancer patients. CONCLUSION: Further studies are needed on the loss of appetite in cancer patients, and specific treatments should be identified according to the pathologic mechanism responsible for anorexia and particularly for taste and smell dysfunctions. Because sufficient nutrition and energy intake can help patients overcome the cancer and its treatment-related complications. PMID- 26881441 TI - Smell and Taste Disorders Resulting from Cancer and Chemotherapy. AB - Malnutrition is common in both adult and pediatric patients undergoing treatment for cancer. Patients commonly attribute difficulties maintaining food intake to an altered taste developed during treatment. This review summarizes what is known about taste and smell dysfunction in patients with undergoing chemotherapy as their main treatment modality. Self-reported taste and smell alterations are prevalent in upwards of 86% of cancer patients. There is some evidence for decreased taste sensitivity in cancer patients when assessed using common gustatory tests. In some patients, taste and smell alterations may continue well after their cancer treatment has been completed. Such disorders can increase distress, reduce appetite and contribute towards poor nutritional status in cancer patients. There remain no effective interventions for improving the appetite or nutritional intake of patients with cancer experiencing taste and smell changes. There is a lack of consistency in assessment methodologies for measuring taste and smell changes in cancer patients and we therefore recommend that future work use well-established methods. Research should also take into account the role of food hedonics, food flavor and texture in assessing the association between taste dysfunction, poor oral intake and malnutrition in cancer patients. Both adult and child cancer patients should be counselled on the potential impact taste and smell dysfunction can have on their appetite and oral intake. PMID- 26881442 TI - Clinical Significance of Umami Taste and Umami-Related Gene Expression Analysis for the Objective Assessment of Umami Taste Loss. AB - Loss of umami taste sensation affects quality of life and causes weight loss and health problems, particularly in the elderly. We recently expanded the use of the filter paper disc method to include assessment of umami taste sensitivity, using monosodium glutamate as the test solution. This test showed high diagnostic performance for discriminating between normal taste function and disorders in sensation of the umami taste, according to established cut-off values. The test also revealed: (1) some elderly patients suffered from specific loss of umami taste sensation with preservation of the other four taste sensations (sweet, salty, sour, and bitter); (2) umami taste disorder caused a loss of appetite and decline in weight, resulting in poor health; (3) appetite, weight and overall health improved after appropriate treatment for umami taste disorder. Because of the subjective nature of the test, however, it may not be useful for patients who cannot express which taste sensation is induced by a tastant, such as those with dementia. Most recently, using tissue samples collected from the tongue by scraping the foliate papillae, we showed that evaluation of umami taste receptor gene expression may be clinically useful for the objective genetic diagnosis of umami taste disorders. PMID- 26881445 TI - Complex Formation Between Lysozyme and Stabilized Micelles with a Mixed Poly(ethylene oxide)/Poly(acrylic acid) Shell. AB - The electrostatic complexation between lysozyme and stabilized polymeric micelles (SPMs) with a poly(acrylic acid) (PAA) or a mixed poly(ethylene oxide)/poly(acrylic acid) (PEO/PAA) shell (SPMs with a mixed shell, SPMMS) and a temperature-responsive poly(propylene oxide) (PPO) core was investigated by means of dynamic, static, and electrophoretic light scattering. The SPMs and different types of SPMMS used resulted from the self-assembly of PAA-PPO-PAA triblock copolymer chains, or PAA-PPO-PAA and PEO-PPO-PEO triblock copolymer chain mixtures (with varying chain lengths and molar ratios) in aqueous solutions at pH 10 and the subsequent cross-linking of their PPO cores via loading and photo cross-linking of pentaerythritol tetraacrylate (PETA). The solution behavior, structure and properties of the formed complexes at pH 7 and 0.01 M ionic strength, were studied as a function of the protein concentration in the solution (the concentration of the stabilized micelles was kept constant) or equivalently the ratio of the two components. The complexation process and properties of the complexes proved to be dependent on the protein concentration, while of particular interest was the effect of the structure of the shell of the SPMs on the stability/solubility of the complexes. Finally, the fluorescence and mid infrared spectroscopic investigation of the structure of the complexed protein showed that, although a small stretching of the protein molecules occurred in some cases, no protein denaturation takes place upon complexation. PMID- 26881446 TI - Predicting therapist effectiveness from their own practice-based evidence. AB - OBJECTIVE: Differences between therapists (therapist effect) are often larger than differences between treatments (treatment effect) in explaining client outcomes, and thus should be considered relevant to providing optimal treatment to clients. However, research on therapist effectiveness has focused largely on global measures of distress as opposed to a multidimensional assessment, and has failed to risk-adjust for client characteristics. The purpose of this study was to examine the stability and predictive validity of therapist effectiveness across multiple outcome domains using risk-adjusted outcomes. METHOD: Initial and follow-up outcome data on the Treatment Outcome Package (Kraus, Seligman, & Jordan, 2005) were collected on 3,540 clients who were treated in naturalistic settings by a sample of 59 therapists. After risk-adjusting outcomes based on case-mix variables using random forest models, outcome data from the first 30 clients of each therapist were used to classify each therapist's effectiveness on 12 outcome domains. These results were then compared with outcome data from the therapist's next 30 clients. RESULTS: Results demonstrated that therapist effectiveness was relatively stable, although somewhat domain specific. Therapists classified as "exceptional" were significantly more likely to remain above average with future cases, suggesting that a therapist's past performance is an important predictor of their future performance. CONCLUSIONS: Clients are likely to experience differential benefit depending on the particular therapist and his or her strengths. Clinical outcomes may be improved by developing the best possible prediction model for each new client and then providing that client with referrals to therapists with well-matched strengths. (PsycINFO Database Record PMID- 26881444 TI - Interrelationship Between Periapical Lesion and Systemic Metabolic Disorders. AB - BACKGROUND: Periapical periodontitis, also known as periapical lesion, is a common dental disease, along with periodontitis (gum disease). Periapical periodontitis is a chronic inflammatory disease, caused by endodontic infection, and its development is regulated by the host immune/inflammatory response. Metabolic disorders, which are largely dependent on life style such as eating habits, have been interpreted as a "metabolically-triggered" low-grade systemic inflammation and may interact with periapical periodontitis by triggering immune modulation. The host immune system is therefore considered the common fundamental mechanism of both disease conditions. METHOD: We have reviewed >200 articles to discuss the interrelationship between periapical lesions and metabolic disorders including type 2 diabetes mellitus, hypertension, and non-alcoholic fatty liver diseases (NAFLD), and their common pathological background in immunology/osteoimmunology and cytokine biology. RESULTS: An elevated inflammatory state caused by metabolic disorders can impact the clinical outcome of periapical lesions and interfere with wound healing after endodontic treatment. Although additional well-designed clinical studies are needed, periapical lesions appear to affect insulin sensitivity and exacerbate non alcoholic steatohepatitis. CONCLUSION: Immune regulatory cytokines produced by various cell types, including immune cells and adipose tissue, play an important role in this interrelationship. PMID- 26881443 TI - Therapeutic Targets for Management of Periodontitis and Diabetes. AB - The increasing incidence of diabetes mellitus (DM) and chronic periodontitis (CP) worldwide imposes a rethinking of individualized therapy for patients with both conditions. Central to bidirectional links between DM and CP is deregulated systemic inflammation and dysfunctional immune responses to altered-self and non self. Control of blood glucose levels and metabolic imbalances associated with hyperglycemia in DM, and disruption of pathogenic subgingival biofilms in CP are currently the main therapeutic approaches for these conditions. Mounting evidence suggests the need to integrate immune modulatory therapeutics in treatment regimens that address the unresolved inflammation associated with DM and CP. The current review discusses the pathogenesis of DM and CP with emphasis on deregulated inflammation, current therapeutic approaches and the novel pro resolution lipid mediators derived from Omega-3 polyunsaturated fatty acids. PMID- 26881447 TI - Cognitive-behavioral therapy augmentation of SSRI reduces cortisol levels in older adults with generalized anxiety disorder: A randomized clinical trial. AB - OBJECTIVES: Elevated cortisol in stress and aging, such as has been seen in late life anxiety disorders, is postulated to accelerate cognitive and physiological decline in this large and increasing population. Selective serotonin-reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are both effective treatments for generalized anxiety disorder (GAD) in older adults. On the other hand, there is very little research examining the effect of combining these therapies on peak cortisol levels. For the current analyses, we examined the effectiveness of CBT augmentation on peak cortisol levels in older adults diagnosed with GAD. METHODS: The sample consisted of 42 individuals with late life GAD who received an acute course of the SSRI escitalopram and then entered a 16-week randomized phase. Twenty-one participants were randomized to receive 16 sessions of CBT in addition to continuing escitalopram and the remaining 21 participants continued on escitalopram without CBT. Generalized estimating equations were performed to assess the effectiveness of CBT augmentation on peak cortisol levels (30 min after waking). RESULTS: Older adults with GAD who received both escitalopram and CBT demonstrated a significant reduction in peak cortisol levels at posttreatment compared to the group who received escitalopram without CBT augmentation. CONCLUSIONS: CBT augmentation of SSRI treatment reduced peak cortisol levels for older adults with GAD. Since persistently high cortisol levels in aging are thought to increase age-related cognitive and medical problems, our findings suggest that there may be a benefit to health and cognition of CBT augmentation for late-life anxiety disorders. PMID- 26881448 TI - The role of setting versus treatment type in alliance within youth therapy. AB - OBJECTIVE: Does the strength of the youth-therapist alliance differ across treatment settings or treatment type? We examined these questions in the context of youth therapy. METHOD: Eighty-nine youths (M age = 10.56, SD = 1.99; 63.70% Caucasian; 52.80% male) diagnosed with an anxiety disorder received (a) manual based individual cognitive-behavioral therapy (ICBT) in a research setting, (b) manual-based ICBT in practice settings, or (c) nonmanualized usual care (UC) in practice settings. Coders, using the Therapy Process Observational Coding System Alliance scale, rated 865 sessions. Youth completed the Therapeutic Alliance Scale for Children at posttreatment. RESULTS: Youth who received ICBT in a research setting had significantly higher observer-rated alliance than youth who received either therapy delivered in practice settings. In practice settings, youth who received ICBT had significantly stronger observer-rated alliance early in treatment than youth in UC, but this difference was not observed at the end of treatment. Similarly, youth-report alliance at posttreatment was significantly higher in ICBT in the research setting, and there was no difference between ICBT and UC delivered in practice settings. Alliance differences largely held when controlling for youth characteristics; however, differences early in treatment between the ICBT groups were no longer statistically significant when controlling for anxiety severity or primary anxiety diagnosis. CONCLUSIONS: Our findings suggest that (a) the alliance may be stronger in research settings, and (b) treatment manuals do not undermine alliance. Future research is required to help pinpoint whether other youth, therapist, or setting factors contribute to the lower alliance seen in practice settings. PMID- 26881449 TI - Mechanisms of personality-targeted intervention effects on adolescent alcohol misuse, internalizing and externalizing symptoms. AB - OBJECTIVE: This study aims to explore the mechanisms of personality-targeted intervention effects on problematic drinking, internalizing and externalizing symptoms. METHOD: As part of a cluster-randomized trial, 1,210 high-risk students (mean age 13.7 years) in 19 London high schools (42.6% White, 54% male) were identified using the Substance Use Risk Profile Scale. Intervention school participants were invited to participate in personality-matched interventions by trained school staff. MacKinnon's products of coefficients method was used to compare 3 complementary mechanism hypotheses, namely, whether early changes in (a) alcohol use, (b) internalizing and externalizing symptoms, or (c) personality during the 6 months postintervention accounted for intervention effects over 2 years. RESULTS: Early intervention effects on drinking behaviors during the 6 months postintervention partially accounted for longer term intervention effects on the onset of binge drinking (95% confidence interval [CI] [-.349, -.062]) and drinking problems (95% CI [-.206, -.016]) over 2 years. Intervention effects on anxiety symptoms and conduct problems were partially mediated by early reductions in depressive symptoms (95% CI [-.013, -.001]; 95% CI [-.047, -.001]), and intervention effects on internalizing symptoms were also partially mediated by reductions in anxiety sensitivity (95% CI [-.003, 0]). CONCLUSIONS: 2-year intervention effects on problematic drinking were largely accounted for by early changes in drinking behaviors, and were not mediated by changes in mental health symptoms or personality risk factors. Early improvements in mood and anxiety sensitivity partially mediated longer term reductions in mental health problems. PMID- 26881450 TI - Crystal Phase Transformation in Self-Assembled InAs Nanowire Junctions on Patterned Si Substrates. AB - We demonstrate the growth and structural characteristics of InAs nanowire junctions evidencing a transformation of the crystalline structure. The junctions are obtained without the use of catalyst particles. Morphological investigations of the junctions reveal three structures having an L-, T-, and X-shape. The formation mechanisms of these structures have been identified. The NW junctions reveal large sections of zinc blende crystal structure free of extended defects, despite the high stacking fault density obtained in individual InAs nanowires. This segment of zinc blende crystal structure in the junction is associated with a crystal phase transformation involving sets of Shockley partial dislocations; the transformation takes place solely in the crystal phase. A model is developed to demonstrate that only the zinc blende phase with the same orientation as the substrate can result in monocrystalline junctions. The suitability of the junctions to be used in nanoelectronic devices is confirmed by room-temperature electrical experiments. PMID- 26881451 TI - Phylogenetic Analysis of Ethiopian HIV-1 Subtype C Near Full-Length Genomes Reveals High Intrasubtype Diversity and a Strong Geographical Cluster. AB - In this study, we characterize HIV-1 subtype C (HIV-1C) strains at the near full length genome (NFLG) level and perform genotypic drug resistance testing (GRT) and genotypic tropism testing (GTT) from Ethiopia (HIV-1CET). Plasma samples (n = 150) were obtained from therapy-naive individuals residing in Addis Ababa, Ethiopia in 2008. HIV-NFLG was performed in a subset of patients (n = 30). GRT (pol) and GTT (V3 env) were performed using in-house methods. GTT was analyzed by PhenoSeq-C. The phylogenetic analysis of the NLFG identified two separate clusters of HIV-1CET, although all strains formed one large overarching cluster together. At NFLG, greater diversity was found among HIV-1CET strains compared to HIV-1C strains from other geographical locations. The geographic clustering was weak in the small subgenomic (pol and env) regions. The primary drug-resistant mutations were identified at a low level (<5%). GTT identified that 12% (12/102) of the patients were predicted to be harboring X4-tropic or both R5/X4-tropic viruses. PMID- 26881452 TI - Oppositely Charged Ions at Water-Air and Water-Oil Interfaces: Contrasting the Molecular Picture with Thermodynamics. AB - The surface-active ions tetraphenylarsonium (Ph4As(+)) and tetraphenylboron (Ph4B(-)) have a similar structure but opposite charge. At the solution-air interface, the two ions affect the surface tension in an identical manner, yet sum-frequency generation (SFG) spectra reveal an enhanced surface propensity for Ph4As(+) compared with Ph4B(-), in addition to opposite alignment of interfacial water molecules. At the water-oil interface, the interfacial tension is 7 mN/m lower for Ph4As(+) than for Ph4B(-) salts, but this can be fully accounted for by the different bulk solubility of these ions in the hydrophobic phase, rather than inherently different surface activities. The different solubility can be accounted for by differences in electronic structure, as evidenced by quantum chemical calculations and NMR studies. Our results show that the surface propensity concluded from SFG spectroscopy does not necessarily correlate with interfacial adsorption concluded from thermodynamic measurements. PMID- 26881453 TI - Biochemical and Molecular Mechanisms of Radioprotective Effects of Naringenin, a Phytochemical from Citrus Fruits. AB - The present study was aimed to evaluate the radioprotective effects of naringenin in vivo using Swiss albino mice as a model system. Oral administration of 50 mg/kg body weight of naringenin for 7 days prior to radiation exposure protected mice against radiation-induced DNA, chromosomal and membrane damage. Naringenin pretreatment also increased the antioxidant status of irradiated mice. Multiple factors operating at cellular and molecular levels led to increased endogenous spleen colonies and survival of mice. Although naringenin induces apoptosis in cancer cells we found that it can protect against radiation-induced apoptosis in normal cells by modulating the expression of p53, Bax, and Bcl-2. The results from the present study indicate that naringenin inhibits the NF-kB pathway and down regulates radiation-induced apoptotic proteins resulting in radioprotection at the cellular, tissue and organism levels. PMID- 26881454 TI - Recent Developments in General Methodologies for the Synthesis of alpha Ketoamides. AB - The alpha-ketoamide motif is widely found in many natural products and drug candidates with relevant biological activities. Furthermore, alpha-ketoamides are attractive candidates to synthetic chemists due to the ability of the motif to access a wide range of functional group transformations, including multiple bond forming processes. For these reasons, a vast array of synthetic procedures for the preparation of alpha-ketoamides have been developed over the past decades, and the search for expeditious and efficient protocols continues unabated. The aim of this review is to give an overview of the diverse methodologies that have emerged since the 1990s up to the present. The different synthetic routes have been grouped according to the way the alpha-ketoamide moiety has been created. Thus, syntheses of alpha-ketoamides proceeding via C(2)-oxidation of amide starting compounds are detailed, as are amidation approaches installing the alpha ketoamide residue through C(1)-N bond formation. Also discussed are the methodologies centered on C(1)-C(2) sigma-bond construction and C(2)-R/Ar bond forming processes. Finally, the literature regarding the synthesis of alpha ketoamide compounds by palladium-catalyzed double-carbonylative amination reactions is discussed. PMID- 26881455 TI - Exploring the Gradient Paths and Zero Flux Surfaces of Molecular Electrostatic Potential. AB - The gradient vector field of molecular electrostatic potential, ?V(r), has remained relatively unexplored in molecular quantum mechanics. The present article explores the conceptual as well as practical aspects of this vector field. A three-dimensional atomic partition of molecular space has been achieved on the basis of zero flux surfaces (ZFSs) of ?V(r). Such ZFSs may completely enclose some of the atoms in the molecule, unlike what is observed in density based atomic partitioning. The demonstration of this phenomenon is elucidated through typical examples, e.g., N2, CO, H2O, H2CO, OF(*), :CH2, and NH3BF3, where the electronegative atoms or group of atoms (group electronegativity) exhibits a closed ZFS of ?V(r) around them. The present article determines an explicit reason for this phenomenon and also provides a necessary and sufficient condition for such a closed ZFS of ?V(r) to exist. It also describes how the potential based picture of atoms in molecules differs from its electron density-based analogue. This work further illustrates the manifestation of anisotropy in the gradient paths of MESP of some molecular systems, with respect to CO, (*)OH, H2O, and H2CO, and points to its potential in understanding the reactivity patterns of the interacting molecules. PMID- 26881456 TI - A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis. AB - New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs. PMID- 26881457 TI - Water Availability for Shale Gas Development in Sichuan Basin, China. AB - Unconventional shale gas development holds promise for reducing the predominant consumption of coal and increasing the utilization of natural gas in China. While China possesses some of the most abundant technically recoverable shale gas resources in the world, water availability could still be a limiting factor for hydraulic fracturing operations, in addition to geological, infrastructural, and technological barriers. Here, we project the baseline water availability for the next 15 years in Sichuan Basin, one of the most promising shale gas basins in China. Our projection shows that continued water demand for the domestic sector in Sichuan Basin could result in high to extremely high water stress in certain areas. By simulating shale gas development and using information from current water use for hydraulic fracturing in Sichuan Basin (20,000-30,000 m(3) per well), we project that during the next decade water use for shale gas development could reach 20-30 million m(3)/year, when shale gas well development is projected to be most active. While this volume is negligible relative to the projected overall domestic water use of ~36 billion m(3)/year, we posit that intensification of hydraulic fracturing and water use might compete with other water utilization in local water-stress areas in Sichuan Basin. PMID- 26881458 TI - Stability Diagrams for Paul Ion Traps Driven by Two-Frequencies. AB - In this paper, we present and discuss stability diagrams for Paul traps driven by two ac voltages. In contrast to a typical Paul trap, here we suggest a secondary ac voltage whose frequency is twice the frequency of the primary one. The ratio between their amplitudes can be used to expand the region of stability and to access different states of motion of trapped ions. This provides a further mechanism to trap, cool, and manipulate single ions and also to improve the experimental framework where ion clouds and crystals can be prepared and controlled. Such approach opens the possibility of designing more sophisticated trapping architectures, leading to a wide variety of applications on ion trap research and mass analysis techniques. PMID- 26881459 TI - Synthesis-Dependent Surface Defects and Morphology of Hematite Nanoparticles and Their Effect on Cytotoxicity in Vitro. AB - In this study, we investigate the toxicity of hematite (alpha-Fe2O3) nanoparticles on the Madin-Darby Canine Kidney (MDCK) cell line. The oxide particles have been synthesized through two different methods and annealing conditions. These two methods, spray precipitation and precipitation, resulted in particles with rod-like and spherical morphology and feature different particle sizes, surface features, and magnetic properties. Through flow cytometry it was found that particle morphology heavily influences the degree to which the nanomaterials are internalized into the cells. It was also found that the ability of the nanoparticles to generate free radicals species is hindered by the formation of tetrahedrally coordinated maghemite-like (gamma-Fe2O3) spinel defects on the surfaces of the particles. The combination of these two factors resulted in variable cytotoxic effects of the hematite nanoparticles synthesized with different conditions. This article highlights the importance on the fabrication method, materials properties, and surface characteristics on the cytotoxicity of hematite nanomaterials. PMID- 26881460 TI - Intraoperative Distal Femoral Fine Wire Traction to Facilitate Intramedullary Nailing of the Femur. AB - Many techniques have been employed to facilitate intramedullary nailing of femur fractures. Maintaining limb length during the operation can be difficult. The authors describe the use of distal femoral fine wire skeletal traction as a technique to maintain reduction while allowing intramedullary nailing of femur fractures. This technique is safe, is effective, and negates the need for a fracture table or an assistant. PMID- 26881461 TI - Effectiveness and Safety of Zoledronic Acid in the Treatment of Osteoporosis. AB - The effectiveness of current treatments for osteoporosis is limited by poor patient compliance. However, a favorable dosing regimen of zoledronic acid (ZA) has the potential to improve patient compliance and thus clinical outcomes. The author conducted a retrospective analysis to examine adherence to and the antiosteoporotic effects of a once-yearly infusion of 5 mg of ZA in Taiwanese patients with osteoporosis for up to 48 months. Five men and 149 postmenopausal women (mean age, 77.1 years) were included. Prior to ZA treatment, 66.2% of patients had fractures; most patients discontinued previous treatments due to compliance or convenience issues. Approximately 85% of patients received at least 2 infusions of ZA. Following ZA treatment, bone mineral density improved from baseline at 12 months (11% from baseline; P=.01) and 48 months (20.7% from baseline; P=.009). In addition there was a significant reduction in mean beta-C telopeptide at all time points from 12 (P<.001) to 36 months (P=.010). New clinical fractures occurred in 16 (10.4%) patients, of which 12 patients experienced a single fracture. Zoledronic acid had an acceptable safety profile; no adverse events were considered to be drug related. Treatment with ZA improved bone health by enhancing bone mineral density and reducing bone turnover, even in high-risk patients. Low fracture rates and high adherence further elucidate the benefits of ZA in the treatment of osteoporosis. PMID- 26881462 TI - Internal Compression Screw Exchange for Reduction of Distal Tibiofibular Syndesmotic Injuries. AB - Traumatic injuries to the distal tibiofibular syndesmosis often accompany ankle fractures. Repair of the syndesmosis is critical for the normal function of the ankle joint. Conventional reduction of the diastasis is achieved with the use of a periarticular reduction clamp. The authors describe an alternative method for reduction of the syndesmosis using a screw exchange technique. This proposed procedure has the prospective of avoiding the multiple potential drawbacks to the use of a reduction clamp. PMID- 26881463 TI - Short-term Outcomes With a Second-Generation Uncemented Stem in Total Hip Arthroplasty. AB - An uncemented stem has been used successfully in total hip arthroplasty for 2 decades, and some implants have been updated. The authors have used second generation uncemented proximal porous coating stems, the Echo Bi-Metric Full Proximal Profile stem (Echo FPP; Biomet, Warsaw, Indiana) and the Echo Reduced Proximal Profile stem (Echo RPP; Biomet). This article reports short-term outcomes with these stems compared with their predecessor, the Bi-Metric stem (Biomet). The authors reviewed 1280 Echo FPP stems, 366 Echo RPP stems, and 1497 Bi-Metric stems. With more than 5 years of follow-up, both the Echo FPP and the Echo RPP stems had 100% survivorship with stem revision as the endpoint, and the Bi-Metric stems also had 100% survivorship for more than 20 years. Average Harris Hip Scores for the Echo FPP, the Echo RPP, and the Bi-Metric stems were 53.3, 49.7, and 51.5 preoperatively, 93.8, 94.6, and 95.2 at 1 year, and 94.0, 95.8, and 95.4 at 3 years postoperatively, respectively. Dislocation after surgery was significantly lower with the Echo FPP and the Echo RPP stems than with the Bi Metric stems, but this was more relevant to the surgical approach and head size. All radiographs of the Echo FPP, the Echo RPP, and the Bi-Metric stems showed proximal femoral remodeling consistent with osseous ingrowth. Distal cortical hypertrophy around the implanted stem and spot-welding were comparably observed in all 3 cohorts. The short-term outcomes of the updated uncemented stems were as excellent as the previously used stem regarding survivorship, complications, and radiographic assessment. PMID- 26881464 TI - Pedicolaminar Fracture-Dislocation. AB - A 28-year-old man presented to a level 1 trauma center with significant cervical spine pain after sliding into third base during a softball game. He struck his head on the thigh of the defensive player and had immediate pain in his neck and arm. He reported no loss of consciousness, no transient tetraplegia/paraplegia, and no loss of bowel and bladder control. After initial imaging, enhanced computed tomography scans were obtained. PMID- 26881465 TI - Short-term Results of Robinson Type 2B2 Clavicular Fractures Treated Conservatively or Surgically. AB - The most frequently treated injuries, representing approximately 82% of all clavicular fractures, involve the midshaft clavicle. Historically, most acute displaced midshaft clavicular fractures were treated nonsurgically. However, the outcomes of nonsurgical treatment have recently been thought to be not as good as expected in the past, and the trend is to treat these fractures surgically. The goal of this study was to evaluate the short-term clinical outcomes of Robinson type 2B2 clavicular fractures treated conservatively vs with locked plate fixation. Among 59 patients included in the study, 30 patients (mean age, 45+/ 13.7 years; range, 30-62 years) treated conservatively were designated as group A, and 29 patients (mean age, 38.8+/-11.1 years; range, 20-60 years) treated with locked plate fixation were designated as group B. All patients were evaluated using Oxford and Constant scoring systems at final follow-up. Mean follow-up was 18 months (range, 12-24 months). In group A, mean Constant score was 70.5+/-15.1 (range, 98-43) and mean Oxford score was 46.6+/-1.3 (range, 49-44) at final follow-up. In group B, mean Constant score was 89.2+/-8 (range, 100-77) and mean Oxford score was 46.5+/-1.2 (range, 48-44) at final follow-up. Callus was detected radiographically in both groups at 6-week follow-up. Patients in groups A and B started active range-of-motion exercises at weeks 6 and 3 after treatment, respectively. Locked plate fixation of Robinson type 2B2 clavicular fractures can be the first treatment option because of good clinical results, low complication rates, and good cosmesis. PMID- 26881466 TI - Use of the G-guide for Measuring Stem Antetorsion During Total Hip Arthroplasty. AB - Implant positioning is one of the critical factors influencing postoperative outcomes in total hip arthroplasty (THA). Several studies have reported that the postoperative antetorsion (AT) measurement for the femoral stem inserted without navigation showed wide variability. The current authors developed a simple instrument, the Gravity-guide (G-guide), for intraoperative assessment of stem AT and adjustment. They evaluated the effectiveness of the G-guide with postoperative computed tomography (CT) examination. Ninety patients (96 hips) who underwent primary THA using the G-guide for stem adjustment were evaluated. The G guide consists of 2 parts: one attached to the lower leg and the other attached to the handle of the rasp. The G-guide was used to evaluate the AT at the time of inserting the final rasp. In addition, the AT value in the G-guide evaluation system required correction by the angle obtained in the preoperative epicondylar view. Intraoperative stem AT was defined as the sum of the intraoperative G-guide value and the correction angle. Postoperative AT was evaluated by CT examination. The discrepancy between the intra- and postoperative measurements was 4.6 degrees +/-4.1 degrees . Acceptable accuracy with discrepancy of less than 5 degrees and 10 degrees was achieved in 66 (69%) hips and 85 (89%) hips, respectively. The use of the G-guide could effectively reduce the variability of stem anteversion compared with manual adjustment. This study proved the effectiveness of the newly developed G-guide system in intraoperative stem AT adjustment. PMID- 26881467 TI - Investigational insulin secretagogues for type 2 diabetes. AB - INTRODUCTION: Insulin secretory defects are a key feature in the pathophysiology of type 2 diabetes (T2D). Classical insulin-secreting agents such as sulfonlyureas stimulate insulin secretion independent of glucose and cause hypoglycemia. Despite the advantages offered by incretin-based therapies, there is still a medical need for developing new insulin secretagogues for treating T2D. AREA COVERED: This article discusses: the new advances in the field of incretin-based therapies, glucokinase (GK) activators, free fatty acid receptor (FFAR) or G protein-coupled receptor (GPR) agonists (GPR40, GPR119, GPR120), imeglimin and some other insulin secretagogues with diverse mechanisms of action still in preclinical development. EXPERT OPINION: New insulin secretagogues should offer major advantages over sulfonylureas and gliptins. The challenge is to avoid uncontrolled insulin secretion and minimize the risk of hypoglycemia, to protect cells from progressive loss of mass and function for a better durability of glucose control, and to offer a good safety profile. Numerous approaches are in development. However, it is too early to decide whether one new pharmacological class will emerge as a clinically useful insulin secretagogue in the near feature. PMID- 26881469 TI - The agentic person: shifting the focus of care. PMID- 26881468 TI - A review of glucosamine for knee osteoarthritis: why patented crystalline glucosamine sulfate should be differentiated from other glucosamines to maximize clinical outcomes. AB - The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for knee osteoarthritis (OA) recommends symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) first line for the medium to long term management of OA, due to their ability to control pain, improve function, and delay joint structural changes. Among SYSADOAs, glucosamine is probably the most widely used intervention. In the present review of glucosamine for knee OA, we have investigated whether the evidence is greater for the patented crystalline glucosamine sulfate (pCGS) preparation (Rottapharm/Meda) than for other glucosamine formulations. Glucosamine is actually widely available in many forms, as the prescription-grade pCGS preparation, generic and over-the-counter formulations of glucosamine sulfate (GS) and food supplements containing glucosamine hydrochloride (GH), which vary substantially in molecular form, pharmaceutical formulation and dose regimens. Only pCGS is given as a highly bioavailable once daily dose (1500 mg) with a proven pharmacological effect. pCGS consistently reaches the plasma levels of around 10 MUM required to inhibit interleukin-1 induced expression of genes involved in the pathophysiology of joint inflammation and tissue destruction, compared with sub-therapeutic levels achieved with GH. It is evident, from careful consideration of the evidence base, that only the pCGS formulation of glucosamine reliably provides an effect size on pain that is higher than that of paracetamol and equivalent to that provided by non-steroidal anti-inflammatory drugs. In comparison, the effect size on pain of non-crystalline GS preparations and GH from randomized controlled trials is repeatedly demonstrated to be zero. In addition, there is evidence that chronic administration of pCGS has disease modifying effects, with a reduction in the need for total joint replacement surgery lasting for at least 5 years after treatment cessation. Consequently, the pCGS preparation (Rottapharm/Meda) is the logical choice, with demonstrated medium-term control of pain and lasting impact on disease progression. PMID- 26881471 TI - Correction to: Astrobiology 2011;11(10):1041-1052. PMID- 26881470 TI - Martian Superoxide and Peroxide O2 Release (OR) Assay: A New Technology for Terrestrial and Planetary Applications. AB - This study presents an assay for the detection and quantification of soil metal superoxides and peroxides in regolith and soil. The O2 release (OR) assay is based on the enzymatic conversion of the hydrolysis products of metal oxides to O2 and their quantification by an O2 electrode based on the stoichiometry of the involved reactions. The intermediate product O2- from the hydrolysis of metal superoxides is converted by cytochrome c to O2 and by superoxide dismutase (SOD) to 1/2 mol O2 and 1/2 mol H2O2, which is then converted by catalase (CAT) to 1/2 mol O2. The product H2O2 from the hydrolysis of metal peroxides and hydroperoxides is converted to 1/2 mol O2 by CAT. The assay method was validated in a sealed sample chamber by using a liquid-phase Clark-type O2 electrode with known concentrations of O2- and H2O2, and commercial metal superoxide and peroxide mixed with Mars analog Mojave and Atacama Desert soils. Carbonates and perchlorates, both present on Mars, do not interfere with the assay. The assay lower limit of detection, when using luminescence quenching/optical sensing O2 electrodes, is 1 nmol O2 cm(-3) or better. The activity of the assay enzymes SOD and cytochrome c was unaffected up to 6 Gy exposure by gamma radiation, while CAT retained 100% and 40% of its activity at 3 and 6 Gy, respectively, which demonstrates the suitability of these enzymes for planetary missions, for example, on Mars or Europa. PMID- 26881473 TI - Children's Cognitive and Affective Responses About a Narrative Versus a Non Narrative Cartoon Designed for an Active Videogame. AB - OBJECTIVE: This article presents the results of interviews conducted with children regarding their cognitive and affective responses toward a narrative and a non-narrative cartoon. The findings will be used to further explore the role of a narrative in motivating continued active videogame play. MATERIALS AND METHODS: Twenty children (8-11 years old of mixed gender) watched two cartoons (narrative and non-narrative) and were subsequently interviewed. A thematic matrix was used to analyze the interviews. RESULTS: The narrative cartoon (n = 11) was only slightly preferred compared with the non-narrative one (n = 9), with little difference among the participants. The theme categories identified during the analyses were plot, characters, and suggestions. The fight scenes were mentioned by the children as a likeable aspect of the narrative cartoon. In the non narrative cartoon, the vast majority (n = 17) liked the information about physical activity that was provided. The children enjoyed the appearance and personalities of the characters in both cartoons. A discrepancy in the data about the fight scenes (narrative cartoon) and characters (both cartoons) was found among the female participants (i.e., some girls did not like the fight and thought the characters were too aggressive). However, most of the children wanted to see more action in the story, an increase in the number of fight scenes (narrative cartoon), or more information about exercise and examples of exercises they could do (non-narrative cartoon). They also suggested adding a game to the non-narrative cartoon, including more characters, and improving the animation in both cartoons. CONCLUSIONS: The children preferred the narrative cartoon because of the story and the fight. Some gender differences were found, which further studies should investigate. PMID- 26881474 TI - HIV and infant feeding in resource-rich settings: considering the clinical significance of a complicated dilemma. AB - With advances in the care of HIV-positive pregnant women, the likelihood of perinatal transmission is now less than 1%. In resource-rich settings women are instructed to abstain from breastfeeding, as studies have shown that breastfeeding increases the likelihood of infant acquisition of HIV. As practitioners caring for HIV-positive parents, we are now facing growing tension about the complex issues that inform decisions about infant feeding. In the face of changing guidelines and global immigration patterns, simply telling women that breastfeeding is contraindicated may no longer be good enough. We must fully open the lines of communication regarding this important and evolving issue. This commentary will review the clinical, social and cultural considerations that impact decisions regarding infant feeding in the context of HIV. PMID- 26881472 TI - Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches. AB - Pancreatic cancer is one of the most challenging cancers. Whole genome sequencing studies have been conducted to elucidate the underlying fundamentals underscoring disease behavior. Studies have identified a subgroup of pancreatic cancer patients with distinct molecular and clinical features. Genetic fingerprinting of these tumors is consistent with an unstable genome and defective DNA repair pathways, which creates unique susceptibility to agents inducing DNA damage. BRCA1/2 mutations, both germline and somatic, which lead to impaired DNA repair, are found to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Recent studies have elucidated that PARP inhibitors and platinum agents may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. In this review we discuss the characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as a novel treatment approach. PMID- 26881475 TI - Psychometric evaluation of the Posttraumatic Cognitions Inventory (PTCI) in female survivors of sexual assault. AB - The authors of this study evaluated the factor structure, internal consistency, and concurrent and discriminant validity of the Posttraumatic Cognitions Inventory (PTCI; Foa et al. 1999) in a sample of 107 female survivors of sexual assault with a mean age of 29.1 years (SD = 7.7). All participants were recruited between July 2010 and December 2014 from a care center for sexual assault victims in Madrid, Spain. Results supported the three-factor structure of the PTCI: (1) negative cognition about self, (2) negative cognition about the world, and (3) self-blame. The negative cognitions about self and the world subscales showed adequate internal consistency (Cronbach's alpha = 0.92 and 0.82, respectively), as well as good concurrent and discriminant validity. Nevertheless, the subscale measuring self-blame showed poor internal consistency (Cronbach's alpha = 0.75) and discriminant validity. The PTCI presents sound psychometric characteristics and has the potential to contribute to women's sexual posttrauma assessment. PMID- 26881477 TI - Interim decision-making strategies in adaptive designs for population selection using time-to-event endpoints. AB - Adaptive designs in oncology clinical trials with interim analyses for population selection could be used in the development of targeted therapies if a predefined biomarker hypothesis exists. In this article, we consider an interim analysis using overall survival (OS), progression-free survival (PFS), and both OS and PFS, to determine whether the whole population or only the biomarker-positive population should continue into the subsequent stage of the trial, whereas the final decision is made based on OS data only. In order to increase the probability of selecting the most appropriate population at the interim analysis, we propose an interim decision-making strategy in adaptive designs with correlated endpoints considering the post-progression survival (PPS) magnitudes. In our approach, the interim decision is made on the basis of predictive power by incorporating information on OS as well as PFS to supplement the incomplete OS data. Simulation studies assuming a targeted therapy demonstrated that our interim decision-making procedure performs well in terms of selecting the proper population, especially under a scenario in which PPS affects the correlation between OS and PFS. PMID- 26881478 TI - How Formerly Overweight and Obese Individuals Negotiate Disclosure of Their Weight Loss. AB - Overweight and obese individuals frequently experience weight-based stigma, and reducing stigma is one reason people want to lose weight. However, research suggests even after individuals become a normal weight, knowledge of their old body size can result in stigma. Through interviews of 30 formerly overweight or obese individuals and the framework of Communication Privacy Management theory, this study found the vast majority of participants perceived more benefits from disclosing their larger identity than risks, regardless of weight-loss method. Participants revealed their weight loss in order to inspire others, build relationships, or hold themselves accountable. Conversely, a few participants concealed to protect their thinner identity (i.e., they feared stigma) or to avoid coming across as boastful. In contrast to previous studies, this investigation suggests most participants were not dissuaded from revealing their former body size due to a threat of residual stigma. Participants' disclosure was overwhelmingly met with encouraging and supportive responses. PMID- 26881476 TI - Factor XIa inhibitors: A review of the patent literature. AB - INTRODUCTION: Anticoagulants are the mainstay for prevention and/or treatment of thrombotic disorders. Each clinically used anticoagulant is associated with significant adverse consequences, especially bleeding. Factor XIa (FXIa), a key factor involved in the amplification of procoagulation signal, has been suggested as a major target for anticoagulant drug discovery because of reduced risk of bleeding. AREAS COVERED: Our literature search uncovered dozens of industrial and academic patents on the discovery of novel FXIa/FXI inhibitors. Small peptidomimetics, sulfated glycosaminoglycan mimetics, polypeptides, antisense oligonucleotides, and monoclonal antibodies have been developed as inhibitors of FXIa. Although many agents are in early discovery/development phases, the activity and safety of a few have been evaluated in various animal models and in humans. EXPERT OPINION: FXIa is a promising drug target for development of effective anticoagulants with limited bleeding complications. Literature reveals a major trend in the number of patent applications over the last three years. These inhibitors exploit different approaches for target inhibition. Allosteric modulation of FXIa and biosynthetic inhibition of FXI are mechanistically unique. Despite initial results in patients undergoing knee anthroplasty as with antisense oligonucleotides, major advances should be realized, particularly with respect to pharmacokinetics, for FXI/FXIa inhibitors to enter the clinic. PMID- 26881479 TI - Facilitation of facial nerve regeneration using chitosan-beta-glycerophosphate nerve growth factor hydrogel. AB - Conclusion C/GP hydrogel was demonstrated to be an ideal drug delivery vehicle and scaffold in the vein conduit. Combined use autologous vein and NGF continuously delivered by C/GP-NGF hydrogel can improve the recovery of facial nerve defects. Objective This study investigated the effects of chitosan-beta glycerophosphate-nerve growth factor (C/GP-NGF) hydrogel combined with autologous vein conduit on the recovery of damaged facial nerve in a rat model. Methods A 5 mm gap in the buccal branch of a rat facial nerve was reconstructed with an autologous vein. Next, C/GP-NGF hydrogel was injected into the vein conduit. In negative control groups, NGF solution or phosphate-buffered saline (PBS) was injected into the vein conduits, respectively. Autologous implantation was used as a positive control group. Vibrissae movement, electrophysiological assessment, and morphological analysis of regenerated nerves were performed to assess nerve regeneration. Results NGF continuously released from C/GP-NGF hydrogel in vitro. The recovery rate of vibrissae movement and the compound muscle action potentials of regenerated facial nerve in the C/GP-NGF group were similar to those in the Auto group, and significantly better than those in the NGF group. Furthermore, larger regenerated axons and thicker myelin sheaths were obtained in the C/GP-NGF group than those in the NGF group. PMID- 26881480 TI - Cryptic epitope for antibodies should not be forgotten in vaccine design. PMID- 26881481 TI - Divided attention enhances explicit but not implicit conceptual memory: an item specific account of the attentional boost effect. AB - The Attentional Boost Effect (ABE) refers to the counterintuitive finding that words encoded with to-be-responded targets in a divided-attention condition are remembered better than words encoded with distractors. Previous studies suggested that the ABE-related enhancement of verbal memory depends upon the activation of abstract lexical representations. In the present study, we extend this hypothesis by embedding it in the context of a broader perspective, which proposes that divided attention in the ABE paradigm affects item-specific, but not relational, processing. To this purpose, we examined the ABE in the matched tasks of category cued recall (CCRT: explicit memory) and category exemplar generation (CEGT: implicit memory). In addition, study time was varied (500, 1500 or 4000 ms), to further determine whether the attentional boost manipulation could influence late phase elaborative processing. In agreement with the predictions of the item specific account, the results showed that exemplars encoded with targets were recalled better than exemplars encoded with distractors in the CCRT, but not in the CEGT. Moreover, performance in the CCRT increased with study time, whereas the size of the ABE-related enhancement tended to decrease, further confirming that this effect hinges upon early phase encoding processes. PMID- 26881482 TI - The catalytic activity of the iron-coated pumice particles used as heterogeneous catalysts in the oxidation of natural organic matter by H2O2. AB - The oxidative removal of natural organic matter (NOM) from waters was investigated by hydrogen peroxide (H2O2) and iron-coated pumice particles in heterogeneous catalytic oxidation process (HCOP). Removal of trihalomethane (THM) precursors, which is formed THM by the reacts with chloride, was performed with the hydroxyl radicals. Coating the original pumice particles with iron oxides significantly enhanced the removal of NOM with peroxide. The studies were carried out in two sections: (1) decomposition of hydrogen peroxide in pure water with iron-coated pumice and (2) oxidation of THM Precursor (NOM) by hydrogen peroxide with iron-coated pumice. The monitored parameters in this study include dissolved organic carbon and trihalomethanes formation potential. The results show that iron-coated pumice catalyst significantly increased the removal efficiency of NOM in the HCOP. The results show that iron-coated pumice catalyst significantly increased the removal efficiency of NOM in the HCOP. Results show that the oxidation of NOM and remaining NOM with H2O2 is improved by the addition of iron coated pumice particles which activate the H2O2 molecule, leading to the formation of hydroxyl radicals in a Fenton-like process. PMID- 26881483 TI - Organizational Responsibility for Age-Friendly Social Participation: Views of Australian Rural Community Stakeholders. AB - This qualitative study critically explores the barriers experienced by diverse rural community stakeholders in facilitating environments that enable age friendly social participation. Twenty-six semi-structured interviews were conducted across two rural Australian communities with stakeholders from local government, health, social care, and community organizations. Findings identify that rural community stakeholders face significant difficulties in securing resources for groups and activities catering to older adults, which subsequently impacts their capacity to undertake outreach to older adults. However, in discussing these issues, questions were raised in relation to whose responsibility it is to provide resources for community groups and organizations providing social initiatives and whose responsibility it is to engage isolated seniors. These findings provide a much-needed critical perspective on current age friendly research by acknowledging the responsibilities of various macro-level social structures-different community-level organizations, local government, and policy in fostering environments to enable participation of diverse rural older adults. PMID- 26881484 TI - Conjugate Haemophilus influenzae type b vaccines for sickle cell disease. AB - BACKGROUND: People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease. OBJECTIVES: The primary objective was to determine whether Haemophilus influenzae type b conjugate vaccines reduce mortality and morbidity in children and adults with sickle cell disease.The secondary objectives were to assess the following in children and adults with sickle cell disease: the immunogenicity of Haemophilus influenzae type b conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search: 23 November 2015. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing Haemophilus influenzae type b conjugate vaccines with placebo or no treatment, or comparing different types of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: No trials of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease were found. MAIN RESULTS: There is an absence of evidence from randomised controlled trials relating to the subject of this review. AUTHORS' CONCLUSIONS: There has been a dramatic decrease in the incidence of invasive Haemophilus influenzae type b infections observed in the post-vaccination era in people with sickle cell disease living in high-income countries. Therefore, despite the absence of evidence from randomised controlled trials, it is expected that Haemophilus influenzae type b conjugate vaccines may be useful in children affected with sickle cell disease, especially in African countries where there is a high prevalence of the disease. The implementation of childhood immunisation schedules, including universal Haemophilus influenzae type b conjugate vaccination, may substantially improve the survival of children with sickle cell disease living in low-income countries. We currently lack data to evaluate the potential effect of Haemophilus influenzae type b vaccination among unvaccinated adults with sickle cell disease. Further research should assess the optimal Hib immunisation schedule in children and adults with sickle cell disease. PMID- 26881485 TI - Improvements in HCV-related Knowledge Among Substance Users on Opioid Agonist Therapy After an Educational Intervention. AB - OBJECTIVES: Lack of knowledge about hepatitis C virus (HCV) is a principal barrier to substance users' engagement into care for the infection. As a step toward their increased engagement into HCV care, the objective of this study was to deliver an HCV-related educational intervention to substance users on opioid agonist therapy and to assess the change in HCV-related knowledge after the intervention. METHODS: We designed a comprehensive and interactive hepatitis C related educational intervention, composed of two 30 to 60-minute sessions conducted during 2 consecutive weeks. Patients' knowledge about hepatitis C was assessed immediately before and after the intervention using a 7-item questionnaire. RESULTS: A total of 110 patients completed both educational sessions. Patients' mean age was 54.7 +/- 7.8 years, 58.7% were men, 70.4% African American, and 30% were Hispanic. We observed a significant increase in HCV-related knowledge after completion of the educational intervention. Whereas 65.45% of patients answered 5 or more questions correctly before the intervention, 83.64% had 5 or more questions answered correctly on the posteducational quiz (P < 0.001). Male sex, ever receiving an HCV diagnostic test before the educational intervention, and a higher level of HCV knowledge on the preeducational quiz were found to be significantly associated with HCV-related knowledge after the educational intervention. CONCLUSIONS: Patients' knowledge about hepatitis C was found to be significantly improved after the educational intervention. Therefore, HCV-related education could be the first step toward effective enrollment of patients on opioid agonist therapy into hepatitis C care. PMID- 26881486 TI - Organ donation as an outcome of traumatic cardiopulmonary arrest: A cost evaluation. AB - BACKGROUND: Survival after traumatic cardiopulmonary arrest (TCPA) is rare and requires significant resource expenditure. Organ donation as an outcome of TCPA resuscitation has not yet been included in a cost analysis. The aims of this study were to identify variables associated with survival and organ donation after TCPA, and to estimate the cost of achieving these outcomes. We hypothesized that the inclusion of organ donation as a potential outcome would make TCPA resuscitation more cost-effective. METHODS: Adult patients who required resuscitation for TCPA at a level I trauma center were retrospectively reviewed over 36 months. Data were obtained from medical records, hospital accounting records, and the local organ procurement agency. Outcomes included survival to discharge, neurologic function, and organ donor eligibility. An individual-level state-transition cost-effectiveness model was used to evaluate the cost of TCPA resuscitation with and without organ donation included as an outcome. Incremental cost-effectiveness ratio was calculated to determine additional cost per life saved when organ donation is included. RESULTS: Over the study period, 8,932 subjects were evaluated. Traumatic cardiopulmonary arrest occurred in 237 patients (3%). The mortality rate was 97%. Variables associated with survival included emergency department disposition to the operating room (p < 0.01) and reactive pupils (p < 0.001). Of seven survivors, four were discharged neurologically intact. Of the patients with TCPA, 5% were eligible for organ donation with a procurement rate of 2%. Organ donor eligibility was associated with arrest after arrival to the emergency department (p < 0.01) and transfusion of fresh frozen plasma (p = 0.01). The cost of TCPA resuscitation per survivor was $1.8 million; cost per survivor or life saved by donation was $538,000. The incremental cost-effectiveness ratio was $76,816 per additional life saved including donation as an outcome. CONCLUSION: The decision to pursue resuscitation should continue to be based on the presence of signs of life, especially pupil reactivity and duration of arrest. If the primary objective is survival, organ procurement will be maximized without conflict of interest. Early fresh frozen plasma transfusion may increase successful organ donation. The financial burden of TCPA resuscitation can be mitigated by expanding end points to include organ donation. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III; cost analysis, level V. PMID- 26881487 TI - Recommendations for venous thromboembolism prophylaxis in pediatric trauma patients: A national, multidisciplinary consensus study. PMID- 26881488 TI - Frailty in trauma: A systematic review of the surgical literature for clinical assessment tools. AB - BACKGROUND: Elderly trauma patients have outcomes worse than those of similarly injured younger patients. Although patient age and comorbidities explain some of the difference, the contribution of frailty to outcomes is largely unknown because of the lack of assessment tools developed specifically to assess frailty in the trauma population. This systematic review of the surgical literature identifies currently available frailty clinical assessment tools and evaluates the potential of each instrument to assess frailty in elderly patients with trauma. METHODS: This review was registered with PROSPERO (the international prospective register of systematic reviews, registration number CRD42014015350). Publications in English from January 1995 to October 2014 were identified by a comprehensive search strategy in MEDLINE, EMBASE, and CINAHL, supplemented by manual screening of article bibliographies and subjected to three tiers of review. Forty-two studies reporting on frailty assessment tools were selected for analysis. Criteria for objectivity, feasibility in the trauma setting, and utility to predict trauma outcomes were formulated and used to evaluate the tools, including their subscales and individual items. RESULTS: Thirty-two unique frailty assessment tools were identified. Of those, 4 tools as a whole, 2 subscales, and 29 individual items qualified as objective, feasible, and useful in the clinical assessment of trauma patients. The single existing tool developed specifically to assess frailty in trauma did not meet evaluation criteria. CONCLUSION: Few frailty assessment tools in the surgical literature qualify as objective, feasible, and useful measures of frailty in the trauma population. However, a number of individual tool items and subscales could be combined to assess frailty in the trauma setting. Research to determine the accuracy of these measures and the magnitude of the contribution of frailty to trauma outcomes is needed. LEVEL OF EVIDENCE: Systematic review, level III. PMID- 26881490 TI - Evidence of data quality in trauma registries: A systematic review. AB - BACKGROUND: Trauma registries are clinical databases designed for quality improvement activities and research and have made important contributions to the improvements in trauma care during the last few decades. The effectiveness of trauma registries in improving patient outcomes depends on data quality (DQ). However, our understanding of DQ in trauma registries is limited. The objective of this study was to review evidence of the completeness, accuracy, precision, correctness, consistency, and timeliness of data in trauma registries. METHODS: A systematic review using MEDLINE, EMBASE, Web of Science, CINAHL, and The Cochrane Library was performed including studies evaluating trauma registry DQ based on completeness, accuracy, precision, correctness, consistency, or timeliness. We also searched MEDLINE to identify regional, national, and international trauma registries whose data were used 10 times or more in original studies in the last 10 years; administrators of those registries were contacted to obtain their latest DQ report. Two authors abstracted the data independently. RESULTS: The search retrieved 7,495 distinct published articles, of which 10 were eligible for inclusion. We also reviewed DQ reports from five provincial and international trauma registries. Evaluation was mostly based on completeness with values between 46.8% (mechanism of injury) and 100% (age and sex). Accuracy was between 81.0% (operating room time) and 99.8% (sex). No evidence of data precision or timeliness was available. Correctness varied from 47.6% (Injury Severity Score [ISS]) to 83.2% (Glasgow Coma Scale [GCS] score) and consistency between variables from 87.5% (International Classification of Disease--9th Rev.--Clinical Modification [ICD-9-CM]/Abbreviated Injury Scale [AIS]) to 99.6% (procedure time). CONCLUSION: In the few studies we identified, DQ evaluation in trauma registries was mostly based on completeness. There is a need to develop a standardized and reproducible method to evaluate DQ in trauma registries. Determinants of DQ and the impact of DQ on trauma registry analyses such as benchmarking with quality indicators should also be explored. PMID- 26881491 TI - Simultaneous liver-kidney transplantation or liver transplantation alone for patients in need of liver transplantation with renal dysfunction. AB - PURPOSE OF REVIEW: There have been no well defined guidelines to determine whether a kidney transplant should be offered to liver transplant candidates who have chronic kidney disease (CKD) or prolonged acute kidney injury while awaiting a liver transplant. This article provides a review of current literature on risk factors for CKD progression after liver transplantation alone (LTA) in patients with pretransplant renal dysfunction and the utility of cystatin C (Cyst C) to assess renal function in cirrhotic patients. Studies evaluating risk factors for transplant futility are also discussed. Based on available literature and existing consensus guidelines, a proposed algorithm for simultaneous liver-kidney transplantation (SLKT) or LTA is formulated. RECENT FINDINGS: In LTA recipients with pretransplant renal dysfunction, diabetes mellitus and type 2 hepatorenal syndrome are associated with CKD progression posttransplant. Coexisting diabetes and stages 3-4 CKD increase end-stage renal disease risk. Cyst C may be a better marker of renal function in cirrhotics. In LTA recipients, very high MELD scores and the concomitant presence of multiple comorbidities increase liver transplant futility risk. Similar studies in SLKT recipients are lacking. SUMMARY: Pretransplant diabetes status should be incorporated into future guidelines for SLKT, whereas simultaneous kidney transplantation should be deferred in highest acuity SLKT candidates with high kidney transplant futility risk. Cyst C-based equations may allow clinicians to better select the most appropriate candidates for SLKT or LTA. Further studies are needed. PMID- 26881492 TI - Nutritional strategies to enhance adaptation in intestinal failure. AB - PURPOSE OF REVIEW: This article summarizes the current and potential future nutritional approaches to stimulate adaptation in intestinal failure. Adaptation in this context usually refers to intestinal adaptation but also involves changes in whole body physiology as well as in eating/drinking behavior. RECENT FINDINGS: Adaptation largely depends on residual functional anatomy. Luminal exposure to complex nutrients is the most important trigger for intestinal adaptation. Enteral fat as well as enteral or parenteral short chain fatty acids have a specific stimulatory effect. Zinc and vitamin A status need to be optimized for adaptation to proceed and be maintained. In the context of maintaining sodium and water homeostasis, flushing the remnant intestine because of uncontrolled thirst/drinking must be avoided. Complications of nutritional care such as malnutrition, intestinal failure-associated liver disease, and recurrent line sepsis also need optimal management. SUMMARY: Stimulation by luminal nutrients as well as prophylaxis against and treatment of (nutritional) complications are the cornerstones of adaptation to the short bowel situation. Based on ample data from animal studies but only limited evidence in humans specific nutritional stimulators need to be studied more rigorously. As long as such data are missing they can be tried on an individual basis. PMID- 26881489 TI - The acute respiratory distress syndrome following isolated severe traumatic brain injury. AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is common after traumatic brain injury (TBI) and is associated with worse neurologic outcomes and longer hospitalization. However, the incidence and associated causes of ARDS in isolated TBI have not been well studied. METHODS: We performed a subgroup analysis of 210 consecutive patients with isolated severe TBI enrolled in a prospective observational cohort at a Level 1 trauma center between 2005 and 2014. Subjects required endotracheal intubation and had isolated severe TBI defined by a head Abbreviated Injury Scale (AIS) score of 3 or greater and AIS score lower than 3 in all other categories. ARDS within the first 8 days of admission was rigorously adjudicated using Berlin criteria. Regression analyses were used to test the association between predictors of interest and ARDS. RESULTS: The incidence of ARDS in the first 8 days after severe isolated TBI was 30%. Patients who developed ARDS were administered more crystalloids (4.3 L vs. 3.5 L, p = 0.005) and blood products in the first 12 hours of admission. Patients with ARDS had significantly worse clinical outcomes measured at 28 days, including longer median intensive care unit and hospital stays (4 days vs. 13 days, p < 0.001, and 7.5 days vs. 14.5 days, p < 0.001, respectively). In unadjusted logistic regression analyses, the odds of developing ARDS were significantly associated with head AIS score (odds ratio [OR], 1.8; p = 0.018), male sex (OR, 2.9; p = 0.012), and early transfusion of platelets (OR, 2.8; p = 0.003). These associations were similar in a multivariate logistic regression model. CONCLUSION: In the era of balanced hemostatic resuscitation practices, severity of head injury, male sex, early crystalloids, and early transfusion of platelets are associated with a higher risk of ARDS after severe isolated TBI. Early transfusion of platelets after severe TBI may be a modifiable risk factor for ARDS, and these findings invite further investigation into causal mechanisms driving this observed association. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26881493 TI - Pharmacological strategies to enhance adaptation in intestinal failure. AB - PURPOSE OF REVIEW: Intestinal failure because of more or less extensive resection of parts of the small and large intestine (short bowel syndrome) results from the reduction of absorptive surface of the remaining intestine and frequently results in dependence on parenteral nutrition. Parenteral nutrition, although lifesaving, is associated with short and long-term complications as well as with reduced quality of life and overall survival. RECENT FINDINGS: Pharmacological enhancement of the physiological intestinal adaptive response by subcutaneous application of the glucagon-like peptide 2 analogue teduglutide results in an improved, hyperadaptive response. This is reflected by decreased parenteral calorie and fluid requirements, decreased parenteral nutrition infusion days per week including complete weaning off parenteral nutrition with complete oral autonomy, improved quality of life, and metabolic and nutritional stability. SUMMARY: The advent of teduglutide as an authority-approved specific medication for intestinal failure in parenteral nutrition-dependent short bowel syndrome offers an effective and beneficial treatment for these patients. As a result, patients are more stable whether for medical or further surgical management including intestinal transplantation. Long-term efficacy and safety still have to be proven. PMID- 26881494 TI - Intramolecular structure and energetics in supercooled water down to 255 K. AB - We studied the structure and energetics of supercooled water by means of X-ray Raman and Compton scattering. Under supercooled conditions down to 255 K, the oxygen K-edge measured by X-ray Raman scattering suggests an increase of tetrahedral order similar to the conventional temperature effect observed in non supercooled water. Compton profile differences indicate contributions beyond the theoretically predicted temperature effect and provide a deeper insight into local structural changes. These contributions suggest a decrease of the electron mean kinetic energy by 3.3 +/- 0.7 kJ (mol K)(-1) that cannot be modeled within established water models. Our surprising results emphasize the need for water models that capture in detail the intramolecular structural changes and quantum effects to explain this complex liquid. PMID- 26881496 TI - Development and Preliminary Validation of the Drinking Expectancy Sexual Vulnerabilities Questionnaire (DESV-Q): A Purpose-Specific Instrument for Rape Perception Research. AB - BACKGROUND: Alcohol expectancies likely play a role in people's perceptions of alcohol-involved sexual violence. However, no appropriate measure exists to examine this link comprehensively. OBJECTIVE: The aim of this research was to develop an alcohol expectancy measure which captures young adults' beliefs about alcohol's role in sexual aggression and victimization. METHOD: Two cross sectional samples of young Australian adults (18-25 years) were recruited for scale development (Phase 1) and scale validation (Phase 2). In Phase 1, participants (N = 201; 38.3% males) completed an online survey with an initial pool of alcohol expectancy items stated in terms of three targets (self, men, women) to identify the scale's factor structure and most effective items. A revised alcohol expectancy scale was then administered online to 322 young adults (39.6% males) in Phase 2. To assess the predictive, convergent, and discriminant validity of the scale, participants also completed established measures of personality, social desirability, alcohol use, general and context-specific alcohol expectancies, and impulsiveness. RESULTS: Principal axis factoring (Phase 1) and confirmatory factor analysis (Phase 2) resulted in a target-equivalent five-factor structure for the final 66-item Drinking Expectancy Sexual Vulnerabilities Questionnaire (DESV-Q). The factors were labeled (1) Sexual Coercion, (2) Sexual Vulnerability, (3) Confidence, (4) Self-Centeredness, and (5) Negative Cognitive and Behavioral Changes. The measure demonstrated effective items, high internal consistency, and satisfactory predictive, convergent, and discriminant validity. CONCLUSIONS: The DESV-Q is a purpose-specific instrument that could be used in future research to elucidate people's attributions for alcohol-involved sexual aggression and victimization. PMID- 26881497 TI - Liver Transplantation for Propionic Acidemia. PMID- 26881498 TI - Theory of spin Hall magnetoresistance (SMR) and related phenomena. AB - We review the so-called spin Hall magnetoresistance (SMR) in bilayers of a magnetic insulator and a metal, in which spin currents are generated in the normal metal by the spin Hall effect. The associated angular momentum transfer to the ferromagnetic layer and thereby the electrical resistance is modulated by the angle between the applied current and the magnetization direction. The SMR provides a convenient tool to non-invasively measure the magnetization direction and spin-transfer torque to an insulator. We introduce the minimal theoretical instruments to calculate the SMR, i.e. spin diffusion theory and quantum mechanical boundary conditions. This leads to a small set of parameters that can be fitted to experiments. We discuss the limitations of the theory as well as alternative mechanisms such as the ferromagnetic proximity effect and Rashba spin orbit torques, and point out new developments. PMID- 26881500 TI - Global trends in specialist training, certification, and regulation of oncology practice and its implications for the developing world. PMID- 26881501 TI - Uncomfortable bedfellows: Whole brain radiation therapy and neurocognition in animal and human studies. PMID- 26881499 TI - One-pot multienzyme (OPME) systems for chemoenzymatic synthesis of carbohydrates. AB - Glycosyltransferase-catalyzed enzymatic and chemoenzymatic syntheses are powerful approaches for the production of oligosaccharides, polysaccharides, glycoconjugates, and their derivatives. Enzymes involved in the biosynthesis of sugar nucleotide donors can be combined with glycosyltransferases in one pot for efficient production of the target glycans from simple monosaccharides and acceptors. The identification of enzymes involved in the salvage pathway of sugar nucleotide generation has greatly facilitated the development of simplified and efficient one-pot multienzyme (OPME) systems for synthesizing major glycan epitopes in mammalian glycomes. The applications of OPME methods are steadily gaining popularity mainly due to the increasing availability of wild-type and engineered enzymes. Substrate promiscuity of these enzymes and their mutants allows OPME synthesis of carbohydrates with naturally occurring post glycosylational modifications (PGMs) and their non-natural derivatives using modified monosaccharides as precursors. The OPME systems can be applied in sequence for synthesizing complex carbohydrates. The sequence of the sequential OPME processes, the glycosyltransferase used, and the substrate specificities of the glycosyltransferases define the structures of the products. The OPME and sequential OPME strategies can be extended to diverse glycans in other glycomes when suitable enzymes with substrate promiscuity become available. This Perspective summarizes the work of the authors and collaborators on the development of glycosyltransferase-based OPME systems for carbohydrate synthesis. Future directions are also discussed. PMID- 26881502 TI - Is thyroid gland an organ at risk in breast cancer patients treated with locoregional radiotherapy? Results of a pilot study. AB - BACKGROUND: Aim was to evaluate the dose distribution within the thyroid gland its association with hypothyroidism in breast cancer (BC) patients receiving supraclavicular (SC) radiation therapy (RT). MATERIALS AND METHODS: Consecutive 40 BC patients with baseline normal thyroid function tests (TFTs), were randomized into two groups: (a) Adjuvant chest wall/breast with SC-RT (20 patients) and (b) control group (adjuvant chest wall/breast RT only); 20 patients. The thyroid gland was contoured for each patient. Each patient's dose volume histogram (DVH), mean thyroid volume, the volume percentages of the thyroid absorbing respectively 5, 10, 20, 30, 40, and 50 Gy (V5, V10, V20, V30, V40, and V50), and Dmean (average dose in whole volume of thyroid) were then estimated. TFTs were performed at the time of the last follow-up and compared. RESULTS: Mean thyroid volume of cohort was 19.6 cm(3) (4.02-93.52) and Dmean of thyroid gland in SC-RT and control group was 25.8 Gy (16.4-52.2) and 5.6 Gy (0.7 12.8), respectively. Median values of V5, V10, V20, V30, V40, and V50 were 54%, 51%, 42.8%, 30.8%, 27.8%, and 7.64%, respectively, in SC-RT as compared to control group (V5;4.9%, V10;2.4%, V20;1.75%, V301%, V40;0%, and V50;0%, respectively) with P < 0.0001. At 52 months, a majority of patients (90%) had a normal thyroid function whereas four patients (10%) had hypothyroidism; 3/20 (15%) patients in SC-RT and 1/20 (5%) in control group with P < 0.001. Significant prognostic factors were; SC-RT (P = 0.001), V30 above 50% (P = 0.001), and smaller thyroid volume (P = 0.03). CONCLUSION: The risk of hypothyroidism in BC patients after SC-RT depends on the thyroid gland volume and V30 >50% and the risk can be minimized by thyroid gland shielding during RT. PMID- 26881503 TI - Evaluation of on-board imager cone beam CT hounsfield units for treatment planning using rigid image registration. AB - PURPOSE: To evaluate the on-board imager cone beam CT (OBI-CBCT) Hounsfield units (HUs) for treatment planning. MATERIALS AND METHODS: The HU-electron density (eD) calibration for CBCT, the CATphan504 phantom was used, and the CBCT HU (HUCBCT) consistency was studied by analyzing the CBCT images of Rando phantom and compared with planning CT. The latter study was also performed on CBCT images of 10 H&N patients. For comparison, the structures contoured and treatment plans generated on CT were transferred on to the CBCT after registration. The treatment plans were compared using gamma (g) index analysis and the plan comparison dose volume histograms (DVHPlanComp). RESULTS: Although the HU-eD calibration curves of both the planning CT and CBCT were found to be linear, differences in mean HU values were found in the region of interest (ROI) corresponding to Acrylic, Derlin, and Teflon, viz., 144 +/- 11 HU, 193 +/- 5 HU, and 257 +/- 7 HU respectively. For all the cases, the consistency and reproducibility of HUCBCT values for low density medium agreed the HU CT except at regions of high density. Overall g-evaluation showed more than 94% pixels pass rate and DVH results showed small difference in the DVHPlanComp, Rando, and large differences in DVHPlanComp, patient for structures contoured at peripheral regions (PV) of CBCT images. CONCLUSIONS: We conclude that the pixel-to-pixel HU corrections for entire range of eD are not necessary for OBI-CBCT images. Application of local correction in the high-density and penumbral regions would facilitate the use of CBCT images for routine treatment planning. PMID- 26881504 TI - Contrast-enhanced ultrasonography in qualitative diagnosis of sentinel lymph node metastasis in breast cancer: A meta-analysis. AB - AIM: This meta-analysis aims to determine the accuracy of contrast-enhanced ultrasonography (CEUS) in the qualitative diagnosis of metastatic sentinel lymph node (SLN) for patients with breast cancer. MATERIALS AND METHODS: We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases. All analyses were calculated using the STATA software, version 12.0 (Stata Corp, College Station, TX, USA). We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratios (LR + /LR-), diagnostic odds ratio (DOR) and receiver operating characteristic (SROC) curve. Thirteen articles that met all inclusion criteria were included in this meta-analysis. RESULTS: A total of 876 breast cancer patients were assessed, including 372 patients with metastatic SLN and 504 patients without metastatic SLN. All SLN were histologically confirmed after conducting CEUS. The pooled Sen was 0.80 (95%CI = 0.76-0.84); the pooled Spe was 0.94 (95% CI = 0.91-0.96). The pooled LR + was 6.28 (95%CI = 3.61-10.92); the pooled negative LR - was 0.218 (95% CI = 0.10-0.31). The pooled DOR of CEUS in qualitative diagnosis of SLN metastasis was 49.10 (95% CI = 27.89-86.45). The area under the SROC curve was 0.937 (standard error [SE] =0.0128). CONCLUSIONS: Our meta-analysis suggests that CEUS may have high a diagnostic accuracy in testing for metastatic SLN in breast cancer. Thus, CEUS may be a good tool for differential diagnosis between metastatic and non-metastatic SLN. PMID- 26881505 TI - Radiotherapy concurrent with weekly gemcitabine after transurethral tumor resection in muscle invasive bladder cancer. AB - OBJECTIVE: In this report, we determined the efficacy and the toxicity of low dose weekly gemcitabine with radiotherapy, in medically unfit or refused surgery muscle-invasive bladder cancer (BC) patients. MATERIALS AND METHODS: From 2008 to 2012, 15 patients were included into the retrospective analysis. Weekly gemcitabine was administered at a rate of 50 mg/m(2) with a median dose of 63 Gy radiotherapy. RESULTS: The median age was 69 (range, 55-86). Median follow-up was 15 months (range, 5-53 months). A complete response was achieved in 12 patients (80%). Median progression free survival and overall survival were 15 months (range, 7-23 months) and 18 months (range not calculated), respectively. Local recurrence was found in 3 patients (20%) and distant recurrence was found in 5 patients (33.3%) for the entire group. While salvage surgery was performed on 1 patient, salvage chemotherapy was delivered for 4 patients. Treatment was well tolerated, there was no treatment interruption or instances of toxic death. A serious toxicity (grade 3) cystitis was seen in only 1 patient. CONCLUSIONS: Multimodality treatment of muscle invasive BC proved a feasible and effective treatment option. Gemcitabine based chemoradiation is an active treatment option with a low toxicity profile for patients with muscle invasive BC, who are not suitable medically or refused to surgery. PMID- 26881506 TI - Tumor suppressive effects of WEE1 gene silencing could not enhance immunopotentiation effects of CD80 and 4-1BBL co-stimulation in human T cells. AB - BACKGROUND: Activation of T cells against tumors by recruiting co-stimulatory molecules has been an attractive approach for cancer immunotherapy. Reports suggested that targeting different genes in tumors might also boost T cell mediated tumor destruction. AIMS: We investigated whether in vitro WEE1 gene silencing in MDA-MB-468 and MCF7 breast cancer cell lines could enhance immunopotentiating effects of CD80 and 4-1BBL co-stimulation in human T cells. MATERIALS AND METHODS: WEE1 gene was specifically silenced in the cancer cells using shRNA technology. The co-stimulatory molecules were over-expressed on the surface of the cancer cells by recombinant non-replicative adenoviruses. The immune reaction of T cells in the co-culture with tumor cells was studied. IFN-g production was assessed by intracellular staining of T cells. To assess cytotoxic activity of CD8+ T cells, the CD107a mobilization-degranulation assay was performed. Expression of granzyme B, perforin and fasl were examined by real time PCR. RESULTS: T cell dual co-stimulation led to a significant increase in the frequency of IFN-g producing cells and higher percentages of degranulation in CD8+ T cells. It also resulted in higher expression levels of the cytotoxicity related genes. WEE1 gene silencing in the target cells alone however, could not produce significant immune reactivation in the cultured T cells. Likewise, the immune responses of T cells neither improved nor suppressed when dually co stimulated PBMCs were exposed to the cancer cells with silenced WEE1. CONCLUSIONS: In spite of antitumor effects of WEE1 silencing, combination of this approach with immune co-stimulation could not boost the reactivity of cultured T cells against the tested breast cancer cells. PMID- 26881507 TI - Combination of survivin siRNA with neoadjuvant chemotherapy enhances apoptosis and reverses drug resistance in breast cancer MCF-7 cells. AB - BACKGROUND: Chemotherapeutic resistance is a main problem in clinical breast cancer therapy. The purpose of our study is to investigate whether the combination of neoadjuvant chemotherapy and survivin siRNA treatment could enhance the therapeutic effect of neoadjuvant chemotherapy using paclitaxel or epirubicin. MATERIALS AND METHODS: The molecular cloning technique was applied to construct the expression vector of siRNA against survivin. Effectene Transfection Reagent was used to transfect plasmids to MCF-7 cells. Survivin expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blot methods. The effect of paclitaxel or epirubicin, with or without the combination of survivin siRNA treatment, on drug susceptibility of MCF-7 cells was detected by CCK-8 assay. MCF-7 cell apoptosis was detected by Flow Cytometry. RESULTS: Survivin siRNA effectively inhibited the expression of Survivin RNA and protein levels (P < 0.05). Both paclitaxel and epirubicin can suppress the proliferation of MCF-7 cells and induce apoptosis to a certain degree respectively. The combination of survivin siRNA with the two chemotherapy drugs significantly enhanced both effects of the two chemotherapeutics respectively (P < 0.05). CONCLUSION: Survivin siRNA combined with the neoadjuvant chemotherapy can significantly enhance the sensitivity of MCF-7 cells to chemotherapeutics and cell apoptosis. This technology has important potential value in the therapeutic study of breast cancer. PMID- 26881508 TI - Prospective randomized trial to compare accelerated (six fractions a week) radiotherapy against concurrent chemoradiotherapy (using conventional fractionation) in locally advanced head and neck cancers. AB - BACKGROUND: Concurrent chemoradiation (CCRT) is currently considered to be the standard of care in locally advanced head and neck cancer. The optimum radiotherapy schedule for best local control and acceptable toxicity is not yet clear. We aimed at shortening of treatment time by using accelerated radiation, thereby comparing the disease response, loco-regional tumor control and tolerability of accelerated radiation (six fractions per week) against CCRT in locally advanced head and neck cancer. MATERIALS AND METHODS: We conducted the prospective randomized study for a period of 2 years from June 2011 to May 2013 in 133 untreated patients of histologically confirmed squamous cell carcinoma of head and neck. Study group (66 patients) received accelerated radiotherapy with 6 fractions per week (66Gy/33#/51/2 weeks). Control group (67 patients) received CCRT with 5 fractions per week radiation (66 Gy/33#/61/2 weeks) along with intravenous cisplatin 30 mg/m(2) weekly. Tumor control, survival, acute and late toxicities were assessed. RESULTS: Median overall treatment time was 38 days and 45 days in the accelerated radiotherapy and concurrent chemoradiation arm, respectively. At a median follow up of 12 months, 41 patients (62.1%) in the accelerated radiotherapy arm and 47 patients (70.1%) in the CCRT arm were disease free (P = 0.402). Local disease control was comparable in both the arms. Acute toxicities were significantly higher in the CCRT arm as compared with accelerated radiotherapy arm. There was no difference in late toxicities between the two arms. CONCLUSION: We can achieve, same or near to the same local control, with lower toxicities with accelerated six fractions per week radiation compared with CCRT especially for Indian population. PMID- 26881509 TI - Malpingian carcinoma of the urinary bladder: A case series. AB - CONTEXT: Malpingian carcinoma (MC) of the bladder is a rare entity. Although distant metastases are very rare it is, usually, diagnosed in the advanced stage, and most patients die. AIMS: The aim was to reveal the characteristics of this tumor and discuss reasons explaining its particular biological behavior. SETTINGS AND DESIGN: The pathologic and clinical characteristics, as well as treatment and outcome of six consecutive cases, were retrospectively studied. SUBJECTS AND METHODS: Medical records of patients with bladder tumors who were treated in our hospital from 2004 onward were reviewed in order to identify those with MC of the bladder. RESULTS: We identified found seven cases. Almost all had locally advanced disease. Three developed visceral metastases and died within few months from the time of diagnosis. CONCLUSIONS: Monitoring protocols required for the early control of local recurrence. PMID- 26881510 TI - Survival and failure patterns in atypical and anaplastic meningiomas: A single center experience of surgery and postoperative radiotherapy. AB - INTRODUCTION: Intracranial meningiomas are the second most common tumor of the CNS. The high-grade tumors are atypical and malignant meningioma comprising 5-7% and 1-3% of all meningiomas. The high-grade meningioma have an aggressive histopathological and clinical behavior. MATERIALS AND METHODS: We retrospectively reviewed 37 patients of high-grade meningioma treated in our institute from 2002 to 2011. Clinical characteristics and treatment modality in form of surgery and radiotherapy (RT) were noted. Statistical analysis was done with regards to progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis. RESULTS: The median age of the patients was 45.0 years. The median duration of symptoms was 6 months. Headache was the most common presenting symptom. Fourteen patients underwent complete excision, while 23 had subtotal excision. Twenty-two patients had World Health Organization (WHO) grade II histology tumors and 15 patients had grade III histology. Median RT dose delivered was 50 Gy for grade II tumors and 54 Gy for grade III tumors. Five-year PFS for grade II and III tumors was 58 and 20%, respectively. Five-year OS for grade II and III tumors was 83 and 23%, respectively. CONCLUSIONS: High-grade meningiomas represent a rare and aggressive neoplasm. The mainstay of therapy is gross total resection (GTR) at the initial surgery. Postoperative adjuvant RT should be offered to all patients, regardless of the degree of resection achieved. Long-term follow-up is important as local recurrences and progression can develop years after the initial treatment. PMID- 26881511 TI - Nodal ratio of positive to excised nodes, but not number of positive lymph nodes is better to predict group to avoid chemotherapy among postmenopausal ER positive, lymph node-positive T1-T2 breast cancer patients. AB - AIM OF STUDY: To identify whether nodal ratio (NR) of positive to excised nodes is superior to number of positive lymph nodes to predict group to avoid chemotherapy among postmenopausal ER-positive, lymph node-positive, T1-T2 breast cancer patients. MATERIALS AND METHODS: Postmenopausal estrogen receptor (ER) positive, lymph node-positive patients who received endocrine therapy (n = 173) with complete baseline data in our hospital between 2000 and 2006 were included. The disease-free survival (DFS) was compared. Survival analysis was performed using Kaplan-Meier method. Cox proportional hazard models were used to evaluate the prognostic value of chemotherapy with different NR for DFS. P--values less than 0.05 were regarded as significant. RESULTS: The median follow-up was 72 months. Three of 13 variables analyzed remained significantly prognostic for survival in the Cox proportional hazards model. These included age (hazard ratio (HR) =1.642, 95% confidence interval (CI) =1.154-2.337, P = 0.006); histological grade (HR = 2.463,95% CI = 1.389-4.367, P = 0.002); and NR (HR = 2.280, 95% CI = 1.113-4.671, P = 0.024). Subgroup analysis by NR status showed that in patients with NR >= 0.20, chemotherapy significantly improves DFS (HR = 0.360, 95% CI = 0.195-0.663, P = 0.001); while in patients with NR < 0.20, chemotherapy did not significantly affect DFS (HR = 0.677, 95% CI = 0.227-2.107, P = 0.493). Radiotherapy is an important factor that improves DFS in lymph node-positive patients, so it is considered in all analysis. CONCLUSION: This retrospective analysis demonstrates that NR of positive to excised nodes, but not number of positive lymph nodes is better to predict group to avoid chemotherapy among postmenopausal ER-positive, lymph node-positive T1-T2 breast cancer patients. PMID- 26881512 TI - Improving the accuracy of target volume delineation by combined use of computed tomography, magnetic resonance imaging and positron emission tomography in head and neck carcinomas. AB - OBJECTIVE: Conformal radiation therapy mandates accurate delineation of target volumes, which requires incorporation of modern imaging modalities like magnetic resonance imaging (MRI) and positron emission tomography (PET) in addition to conventionally used computed tomography (CT). This can resolve discrepancies in target delineation in head and neck carcinomas resulting in better local control. We hereby report the comparison of Gross Tumor Volumes (GTVs) (primary) drawn using PET, CT and MRI and their concordance indices. METHODS AND MATERIAL: Twenty five patients with head and neck cancer were taken into this study. MRI, PET and CT planning scans were done as per standard guidelines. Three sets of primary GTVs namely GTV- PET, GTV-CT and GTV-MRI were contoured on fused images. All the three volumes and concordances among the volumes were analyzed. RESULT: The mean GTV-CT, GTV-PET and GTV-MRI volumes were 29.65 cc +/- 31.27, 32.05 cc +/- 33.75 and 24.85 cc +/- 25.28 respectively. There was a significant difference in the GTV-MRI & GTV-CT volumes (P = 0.023) and GTV-PET & GTV-MRI volumes (P = 0.049). However, there was no significant difference in the GTV-PET & GTV-CT volume (P = 0.468). The mean CI (PET-MRI), CI (CT-MRI) and CI (PET-CT) was 0.42, 0.46 and 0.47 respectively, which depicts a moderate concordance. CONCLUSION: PET and MRI are useful imaging tools in head and neck malignancies and should be used in conjunction with CT scan for improved target volume delineation. PMID- 26881513 TI - Tumor dose enhancement by nanoparticles during high dose rate (192)Ir brachytherapy. AB - AIMS AND OBJECTIVES: The present study aims to evaluate and compare the dose enhancement factor (DEF) of tumor injected with different nanoparticles (NPs) around high dose rate (HDR) (192)Ir brachytherapy source. MATERIALS AND METHODS: Monte Carlo calculations were performed with MCNPX code to determine the DEF caused by in tumor injected with (79)Au, (64)Gd, (26)Fe, and (22)Ti NPs during HDR (192)Ir brachytherapy. The uniform and non-uniform distribution of NPs within tumor was modeled with simple NPs-water mixture, and realistic nano-scale-lattice model. Furthermore, a margin of (79)Au and 64 Gd NPs was implemented around the tumor volume. RESULTS: The increased dose caused by uniformly distributed (79)Au and 64)Gd NPs with 7, 18, and 30 mgr/gr concentrations was 4.7%, 11.8%, 19.4%, and 3.3%, 8.3%, and 18.6%, respectively. For non-uniform distribution, it was 0.4%, 1.2%, 1.9%, and 0.2%, 0.7%, and 1.2%, respectively. Increased tumor dose due to (26)Fe and 22 Ti was not significant. The peripheral-healthy tissue dose as margin with 2, 5, and 8.5 mgr/gr of 7(9)Au and 6(4)Gd increased by 1.3%, 3.6%, 6.5%, and 1.1%, 2.5%, and 4.2%, respectively. Increase the radial depth of tumor (from 1.5 to 5 cm) increase DEF (up to 22.3%). The nano-lattice model underestimated the DEF up to 4% and 3.6% for 79Au and (64)Gd NPs, respectively. CONCLUSION: Injecting of high-Z gold NPs into tumor increases the absorbed dose of tumor irradiated with (192)Ir HDR brachytherapy source. Size, geometry, concentration, and distribution model of NPs and tumor depth are crucial factors to accurately estimate the DEF. PMID- 26881514 TI - Association between CYP1A1 2454A > G polymorphism and colorectal cancer risk: A meta-analysis. AB - BACKGROUND: The aim of our study was to assess the association of CYP1A1 2454A > G polymorphism and colorectal cancer (CRC) risk. MATERIALS AND METHODS: Electronic databases, including PubMed, MEDLINE Springer, Elsevier Science Direct, Cochrane Library, and Google Scholar were searched for relevant trials until December 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analyses were conducted based on geographical region and size of the study samples. RESULTS: Thirteen eligible studies were included in this meta-analysis with 3490 cases and 4076 controls. There were significant associations under the overall ORs for G-allele comparison (G vs. A, pooled OR 1.29, 95% CI 1.03-1.61, P = 0.03), GG versus AA comparison (pooled OR 1.50, 95% CI 1.17-1.91, P < 0.01), recessive model (GG vs. GA + AA, pooled OR 1.52, 95% CI 1.20-1.94, P < 0.01) between CYP1A1 2454A > G polymorphism and CRC risk. Subgroup analyses stratified by geographical region demonstrated an association in Asia and Europe, but not in America. CONCLUSION: This meta-analysis suggests that CYP1A1 2454A > G polymorphism might be associated with susceptibility of CRC and the allele G might increase the CRC risk in Asia and Europe. PMID- 26881515 TI - Dose response characteristics of a novel CCD camera-based electronic portal imaging device comparison with OCTAVIUS detector. AB - AIM: Dosimetric properties of a CCD camera-based Electronic Portal Imaging Device (EPID) for clinical dosimetric application have been evaluated. Characteristics obtained by EPID also compared with commercial 2D array of ion chambers. MATERIALS AND METHODS: Portal images acquired in dosimetry mode then exported raw fluence or uncorrected images were investigated. Integration time of image acquisition mode has adjusted on 1 s per frame. RESULTS: As saturation of camera of the EPID, dose response does not have linear behavior. The slight nonlinearity of the camera response can be corrected by a logarithmic expression. A fourth order polynomial regression model with coefficient of determination of 0.998 predicts a response to absolute dose values at less than 50 cGy. A field size dependent response of up to 7% (0.99-1.06) relative OCTAVIUS detector measurement was found. The EPID response can be fitted by a cubic regression for field size changes, yielded coefficient of determination of 0.999. CONCLUSIONS: These results indicate that the EPID is well suited for accurate dosimetric purposes, the major limitation currently being due to integration time and dead-time in frame acquisition. PMID- 26881516 TI - Conventional vs concomitant boost radiotherapy with concurrent cisplatin in advanced head and neck cancer. AB - AIM OF STUDY: To compare outcome of concomitant boost therapy (CBT) with conventional radiotherapy with cisplatin as a radiosensitizer in advanced head and neck cancer. SUBJECTS AND METHODS: Prospective comparative study was undertaken. Patients were assigned alternately to ArmA (conventional arm) and ArmB (CBT arm), 30 in each arm and total 60 patients were enrolled. RESULTS: Out of 30 patients in conventional Arm A, 13 had complete response (CR; 43.33%), 9 had partial response (PR; 30%), three patients (10%) had stable disease (SD), and five patients (16.66%) had progressive disease (PD). In arm B out of 30 patients, 18 patients (60%) had CR, five patients (16.66%) had partial response (PR), four patients (13.33%) showed SD, and three patients (10%) had PD. There was no statistically significant difference between the two arms for CR (P - value = 0.196). CONCLUSIONS: CBT can be used as an alternative to conventional RT in advanced head and neck cancers which minimize the total duration and the workload can be reduced. The locoregional control with CBT is comparable with the response of conventional RT. PMID- 26881517 TI - Evaluation of dose perturbation at the interface of two different density medium using GAFCHROMIC film EBT2 and Monte Carlo code EGSnrc for Co-60 beam. AB - INTRODUCTION: Accurate dosimetry at the interface of two different density medium (e.g., air cavity in the head and neck cancers and lungs in thoracic region) is a major cause of concern in external beam radiation therapy. It has been observed that there is dose variation in and around air cavities, which occur as a result of the loss of both longitudinal and lateral electronic equilibrium. Heterogeneous structures with spatial differences in functionality and sensitivity for radiation pose challenge to radiation dosimetry. This study is an attempt to evaluate the dose perturbations produced at the interface of two medium for C0-60 gamma radiation. MATERIALS AND METHODS: Low density polyethene foam has been used to mimic air cavity. GAFCHROMIC EBT2 dosimetry film was used for the measurement of dose at different locations. Simulation studies were performed using DOSRZnrc user code that comes with EGSnrc V4 2.4.0. Cylindrical geometry is used for all the simulations. RESULTS AND DISCUSSION: We observed significant variation in dose for smaller fields. There is a dose build down in the backward region and a dose build up in the forward direction. In the region of electronic disequilibrium, dose reduction near interface (proximal end) will have negative impact if target region is embedded there, on the contrary, it would be beneficial if there is normal tissue/critical organ adjacent to it. PMID- 26881518 TI - Clinicopathological characteristics and primary treatment of prostate cancer in a urology unit of Sri Lanka. AB - AIMS: The aim was to describe the clinicopathological characteristics of prostate cancer and the primary treatment modality in a cohort of patients seen in a urology unit of Sri Lanka. MATERIALS AND METHODS: Data were collected prospectively from all patients with newly diagnosed prostate cancer and managed in a urology unit in Sri Lanka from January 2010 to December 2013. Patient's age, clinical presentation, prostate specific antigen (PSA) level, mode of diagnosis, Gleason sum score, stage of the disease and main modality of treatment were recorded and analyzed. RESULTS: There were 278 cases of histologically proven prostate cancer. Mean patient age was 70.5 years. About 50% presented with lower urinary tract symptoms. Only 2% were screening detected cases. Five (2%) patients had a first-degree relative who had prostate cancer. About 81% of patients had a serum PSA above 20 ng/ml. Gleason sum score was 8 or more in 44% of patients. Metastases were found at the time of diagnosis in 60% of patients. Forty-eight patients underwent radical radiotherapy, while seven patients had radical prostatectomy. Most (94%) of the 203 patients who required androgen deprivation therapy had surgical orchiectomy. CONCLUSIONS: Sri Lankans appear to be having a low incidence of prostate cancer, but a larger proportion of high-grade cancers in comparison to the UK and USA. Although genetic differences may exist, a dietary or an environmental factor is more likely to be the cause for these changes. The protective effect of this factor appears to wane as South Asians emigrate and live in UK and USA. PMID- 26881519 TI - Cyclooxygenase-2 expression is associated with elevated aspartate aminotransferase level in hepatocellular carcinoma. AB - BACKGROUND: Cyclooxygenase-2 (COX-2), the inducible rate-limiting enzyme of prostaglandins biosynthesis, is involved in the pathogenesis of many chronic inflammation-related human malignancies including hepatocellular carcinoma (HCC). However, its clinical significance in HCC remains obscure. The aim of our study was to evaluate COX-2 expression in HCC and correlate its expression to both clinicopathological parameters and patients survival. MATERIALS AND METHODS: The present study was conducted on 17 HCC and 21 adjacent nontumor liver tissues obtained from 22 HCC patients underwent hepatectomy. Eight normal liver tissues taken from normal donors and HepG2 cells were used as controls. Total RNA was extracted and COX-2 mRNA was detected by reverse transcription polymerase chain reaction and correlated to the clinicopathological criteria and to patient's survival. RESULTS: COX-2 mRNA was detected in 58.8% of the HCC tissues and in 28.6% of the adjacent nontumor liver tissues. COX-2 expression was significantly associated with elevated levels of serum aspartate aminotransferase (AST) with high specificity for disease detection. There was no significance between COX-2 expression and any of the histopathological criteria. CONCLUSIONS: COX-2 expression may be involved in HCC carcinogenesis with high specificity for disease detection. COX-2 expression is significantly associated with elevated AST levels indicating a mechanism that may correlate both markers. However COX-2 expression seems to be an independent factor with no correlation to any of the histopathological data or patient's survival. PMID- 26881520 TI - Video-assisted thoracoscopic lobectomy for elderly nonsmall cell lung cancer: Short-term and long-term outcomes. AB - BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and the number of elderly patients with nonsmall-cell lung cancer (NSCLC) has risen with increasing life-expectancy. AIMS: To evaluate safety and efficacy of thoracoscopic lobectomy for NSCLC patients above 75 years old. PATIENTS AND METHODS: We reviewed the data of 795 consecutive patients with NSCLC, who underwent video-assisted thoracoscopic lobectomy from January 2006 to December 2013. Patients were divided into two groups: The elderly group aged at least 75 years old (n = 54), the contrast group aged <75 years old (n = 741). The general characteristic, comorbidity, intraoperative observations, complications, operative mortality and long-term survival were compared between the two groups. RESULTS: The elderly group had a higher incidence of squamous cell carcinoma (40.74% vs. 29.69%) and a lower incidence of adenocarcinoma (37.04% vs. 52.63%) than the contrast group (P = 0.083). The ratio of smoking (61.11% vs. 41.97%), preoperative comorbidities (62.96% vs. 38.06%), perioperative blood transfusion (25.93% vs. 13.50%) and thoracic intubation indwelling time (10.3 vs. 8.2 days) in the elderly group were higher (P < 0.01). There was no significant difference in duration of surgery (222.9 vs. 226.6 min), intraoperative blood loss (299.8 vs. 253.5 min), hospital stay (18.2 vs. 15.8 days) or postoperative hospital stay (10.3 vs. 8.4 days) between the two groups. Postoperative morbidities occurred more frequently in the elderly group than the contrast group (24.07% vs. 12.01%, P = 0.018). Thirty-day mortality rate of two groups showed no significant difference (1.85% vs. 0.40%, P = 0.246). The overall survival and recurrence-free survival in the elderly group were comparable with the contrast group (P = 0.114 and 0.092, respectively). CONCLUSIONS: Video-assisted thoracoscopic lobectomy is a safe and reliable approach with acceptable short- and long-term outcome in the elderly. PMID- 26881521 TI - Lymphatic vessel assessment by podoplanin (D2-40) immunohistochemistry in breast cancer. AB - CONTEXT: Lymph node metastasis has an important bearing on the staging of breast cancer. Lymph node metastasis occurs by hematogenous and lymphatic spread. The hematogenous and lymphatic spread can be quantified by the blood vessel and lymphatic vessel density in the intra-tumoral and peri-tumoral zone by specific markers for blood vessels and lymph vessels. AIMS: In this study, we are trying to study the localization of podoplanin in lymph vessels of invasive breast carcinoma, to quantify lymphangiogenesis in tissue sections of invasive breast carcinomas by podoplanin immunohistochemistry (IHC) by D2-40 antibody, and compare it with blood microvessel count using CD-31 antibody and correlating clinicopathologic parameters with the results of IHC. MATERIALS AND METHODS: IHC for biomarkers D2-40 and CD-31 were performed on sections from 30 mastectomy specimens to assess blood vessel and lymphatic vessel density in intra-tumoral and peri-tumoral zone. The data were analyzed using Statistical Package for Social Sciences (SPSS) version 15.0 statistical analysis software. RESULTS: The results showed that both lymph vessel density and blood vessel density increased with the increase in lymph node ratio. Lymph node ratio is the ratio of positive lymph nodes to the total number of lymph nodes removed. CONCLUSION: Taking into account our small sample size, we conclude that a further large-sized study should be carried out to further prove the role of lymphatics in tumor dissemination. New therapeutic options can be developed targeting the lymphatic channels to arrest the lymphatic spread of the breast cancer. PMID- 26881522 TI - Retrospective analysis of third-line chemotherapy in advanced non-small cell lung cancer. AB - BACKGROUND: First- and second-line chemotherapies have been demonstrated to be effective in treatment of patients with inoperable, advanced non-small cell lung cancer (NSCLC), although the role of third-line chemotherapy remains unclear. The present investigation assessed treatment outcomes in patients with advanced NSCLC who received third-line and higher chemotherapy. PATIENTS AND METHODS: This retrospective study included consecutive patients with advanced NSCLC who received at least three lines of systemic chemotherapy. RESULTS: A total of 72 patients who had received third-line or higher chemotherapy were included in the analysis. The median age of patients was 49 years (range 41-76), and there were 13 (18.1%) women and 59 (81.9%) men. Estimated median survival was 26 months. Moreover, overall survival was significantly longer in patients for whom disease control was achieved after second-line chemotherapy compared to those with disease progression (34 vs. 17 months, respectively). Survival after third-line treatment was significantly longer in the group with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at the beginning of third-line therapy compared to patients with a status of 2-3. CONCLUSIONS: In patients with advanced stage NSCLC, administration of third-line and higher systemic chemotherapy may be associated with increase in overall survival. Furthermore, greater increases in overall survival were also observed in patients for whom disease control was achieved after second-line therapy and in those with ECOG performance status of 0 1 before third-line treatment. PMID- 26881523 TI - Contribution of PGR genetic polymorphisms to the pathogenesis of endometrial cancer: A meta-analysis. AB - OBJECTIVE: The aim of this meta-analysis is to identify whether two common genetic polymorphisms (rs1042838 G > T and rs10895068 C > T) in the PGR gene may contribute to the pathogenesis of endometrial cancer. MATERIALS AND METHODS: The MEDLINE (1966 ~ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ~ 2013), CINAHL (1982 ~ 2013), Web of Science (1945 ~ 2013) and the Chinese Biomedical Database (CBM) (1982 ~ 2013) were searched without language restrictions. Meta-analyses were conducted using the STATA software (Version 12.0, Stata Corporation, College Station, Texas, USA). We calculated odds ratio (OR) and its 95% confidence interval (95% CI) to estimate the relationships between PGR genetic polymorphisms and the pathogenesis of endometrial cancer. RESULTS: Six studies with a total of 6,285 patients with endometrial cancer and 12,120 control subjects met the inclusion criteria for the meta-analysis. Our findings suggested that PGR rs1042838 polymorphism was significantly correlated with an increased risk of endometrial cancer (T allele vs. G allele: OR = 1.23, 95% CI: 1.07 ~ 1.42, P = 0.005; GT + TT vs. GG: OR = 1.21, 95% CI: 1.06 ~ 1.40, P = 0.006; TT vs. GG + GT: OR = 1.65, 95% CI: 1.09 ~ 2.49, P = 0.017; TT vs. GG: OR = 1.72, 95% CI: 1.12 ~ 2.65, P = 0.013; TT vs. GT: OR = 1.42, 95% CI: 1.01 ~ 2.00, P = 0.044, respectively). We also observed positive associations between PGR rs10895068 polymorphism and the pathogenesis of endometrial cancer (T allele vs. C allele: OR = 1.15, 95% CI: 1.02 ~ 1.29, P = 0.027; CT + TT vs. CC: OR = 1.14, 95% CI: 1.00 ~ 1.29, P = 0.045, respectively). CONCLUSION: Ethnicity stratified analysis indicated that rs1042838 and rs10895068 polymorphisms in the PGR gene might be strongly related to the pathogenesis of endometrial cancer among Caucasians and mixed populations (all P < 0.05). In conclusion, our findings provide empirical evidence that PGR rs1042838 and rs10895068 polymorphisms may be involved in the pathogenesis of endometrial cancer. PMID- 26881524 TI - Regulation of demethylation and re-expression of RASSF1A gene in hepatocellular carcinoma cell lines treated with NCTD in vitro. AB - BACKGROUND: Hepatocellular carcinoma, a lethal malignant neoplasm with poor prognosis, has dismal results of surgical resection and chemoradiotherapy. Norcantharidin (NCTD), the demethylated analog of cantharidin derived from a traditional Chinese medicine, Mylabris, has been used in the treatment of cancer. However, the detailed mechanisms underlying this process are generally unclear. PURPOSE: The aim of this study was to investigate the mechanism of NCTD-induced apoptosis in HepG2 cells. MATERIALS AND METHODS: Human HepG2 cell lines were treated with NCTD at different concentrations (2.50, 5.00, 10.00, 20.00, 40.00 MUg/mL) for 24 hours. Cell proliferation was evaluated by measurement of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The methylation levels of RASSF1A (Ras-association domain family 1 A) in HepG2 cells were detected by methylation-specific PCR (MSP). The mRNA levels of RASSF1A in HepG2 cells were detected by real-time fluorescent quantitative PCR (RT-PCR). The levels of RASSF1A protein expression of HepG2 cells were detected by Western blotting assay. RESULTS: The inhibition of cell proliferation was observed when treated with NCTD at concentrations (2.5 MUg/mL), and as concentration increased, the proliferation of HepG2 cells was markedly inhibited by NCTD in dose-dependent manners. The levels of methylation of RASSF1A decreased at the increasing concentration of 10, 20 and 40 MUg/mL. The levels of RASSF1A mRNA and protein were decreased when treated with NCTD at the concentrations of 10, 20 and 40 MUg/mL, which were also in a dose-dependent manner. CONCLUSION: NCTD can reverse the methylation state of RASSF1A gene and induce its re-expression, which will provide the theoretical basis for the clinical practice. PMID- 26881525 TI - Doxorubicin enhances (131)I-rituximab induced cell death in Raji cells. AB - AIM: There are various therapeutic modalities of treatment for non-Hodgkin's lymphoma, but with certain limitations, hence, investigating the scope of combined therapeutic approach. MATERIALS AND METHODS: In this article, cellular toxicity, apoptosis and expression of mitogen-activated protein kinase signaling pathway proteins were investigated in Raji cells preincubated with doxorubicin followed by (131)I-rituximab (rituximab radiolabeled with Iodine-131) treatment. RESULTS: It was found that the (131)I-rituximab in combination with doxorubicin showed a higher amount of cell toxicity and apoptosis compared to respective controls. Expression of anti-apoptotic protein (B-cell lymphoma-extra-large) was downregulated and cleavage of poly (ADP-ribose) polymerase, a marker of apoptosis was higher in cells treated with doxorubicin (2 MUg/mL) and 131 I-rituximab (P <= 0.05). Moreover, in these cells the basal level of expression of p42/44 and p38 were increased while its phosphorylation was decreased. CONCLUSION: These results suggest that doxorubicin has the potential to sensitize (131)I-rituximab induced cell death in Raji cells. PMID- 26881526 TI - Adult rhabdomyosarcoma: Clinical presentation, treatment, and outcome. AB - OBJECTIVE: Rhabdomyosarcoma (RMS) in adults is a rare malignancy. The objective of our study was to determine presentation, treatment, patterns of failure, and outcome in this disease. MATERIALS AND METHODS: A retrospective analysis of 25 patients of adult (>16 years) RMS who were treated at our institute from 2000 to 2009 was carried out. Tumors were classified according to the Intergroup Rhabdomyosarcoma Study (IRS) staging. All patients were treated with multimodality treatment except for three patients who received chemotherapy as the only modality. RESULTS: The median age was 19 years (range, 16-68 years). The most common site was head and neck (52%) followed by extremities (24%), genitourinary (20%), and retroperitoneal RMS (4%). Three out of 25 patients presented with distant metastasis. With a median follow-up of 45 months, the 5 year overall survival (OS) rate was 45%. The 5-year local control (LC) rate was 53%. IRS grouping and complete response after primary therapy were predictors of a better survival. CONCLUSIONS: RMS in adults have poor prognosis as compared to childhood RMS. Adult RMS should therefore be treated aggressively with multidisciplinary approach comprising of surgery, radiation, and chemotherapy to achieve cure and prolonged survival. PMID- 26881527 TI - Post chemotherapy extravasation injuries: Hypogastric flap for reconstruction of wounds over dorsum of hand. AB - CONTEXT: Management of extravasation injuries over the dorsum of hand after administration of chemotherapeutic agents. AIM: To study the results of hypogastric flap reconstruction in chemotherapy extravasation wounds over dorsum of hand. SETTINGS AND DESIGN: Retrospective study. SUBJECTS AND METHODS: At our center over 3-years period, 32 patients were treated for chemotherapy extravasation wounds. Out of these 32 patients, seven had wound over dorsum of hand. There were five males and two females, and their mean age was 45 years (range, 19 - 64 years). These patients with wound over the dorsum of hand were treated with multiple debridements and hypogastric flap reconstruction. RESULTS: The mean interval between extravasation wound and surgical treatment was 6.28 days (range, 4 - 10). The mean size of extravasation wound defect was 14 * 8 (range, 12 * 7 to 18 * 8). Non-dominant hand was involved in six patients and dominant hand in one patient. In four patients, the hypogastric flap was supplemented with skin graft. The hypogastric flap settled well in all patients and enabled a good wound cover. Complete division of the flap and final insetting was done under local anesthesia after 3 weeks; this was followed by limb mobilization exercises. Contour difference over the dorsum of hand was present in all the cases. The range of movement of the hand was functionally restricted in one patient. No patient in current series developed wound infection. CONCLUSION: Hypogastric flap is a reliable flap to cover wound over dorsum of hand after extravasation of chemotherapeutic agents. PMID- 26881528 TI - Se-methylselenocysteine suppresses the growth of prostate cancer cell DU145 through connexin 43-induced apoptosis. AB - CONTEXT: Se-methylselenocysteine (MSC), as a chemopreventive agent, shows antitumor effects in some cancer models, but its mechanism is still unclear. AIMS: This study is to explore whether MSC induces apoptosis in prostate cancer (PCa) cells DU145 through connexin 43 (Cx43) activation. SETTINGS AND DESIGN: The experiment was performed in a PCa cell line model DU145 and using a series of biological assay methods to investigate the regulating pathway from MSC through Cx43 to downstream molecules, demonstrating an important role of Cx43 in PCa development and as a potential treatment target. MATERIALS AND METHODS: The human PCa cell line DU145 was used as a model. The effects of MSC on Cx43 expression were examined by reverse transcription-polymerase chain reaction, western blot; effects on cell growth and proliferation were determined by WST-1 and colony formation assay; small interfering ribonucleic acid was used to evaluate the direct contribution of Cx43 to cancer cell apoptosis. STATISTICAL ANALYSIS USED: Student's t-test was used to calculate the difference between the groups in SPSS software. RESULTS: Results showed that MSC inhibited the growth and colony formation of the DU145 cells; MSC induced cell apoptosis by increasing Cx43 expression at messenger ribonucleic acid and protein levels; MSC decreased B-cell lymphoma-2 (Bcl-2) and increased bad levels of DU145 cells. CONCLUSIONS: As a conclusion, MSC exerts pro-apoptosis effects through increasing Cx43 expression, which in turn down-regulates Bcl-2 and up-regulates bad expression. PMID- 26881529 TI - Protein-protein interaction networks and modules analysis for colorectal cancer and serrated adenocarcinoma. AB - PURPOSE: To screen key modules and explore the potential mechanism of conventional colorectal cancer (CRC) and colorectal serrated adenocarcinoma (SAC). MATERIALS AND METHODS: The microarray data of GSE36758 and GSE8671 were downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in SAC versus colon carcinoma (CC) and CC versus normal control (NC) group were analyzed and the protein-protein interaction (PPI) networks for DEGs were constructed. The modules of PPI networks were further analyzed and the function enrichment analysis of all enrolled DEGs was carried out based on ToppGene database. RESULTS: Total eight DEGs (SAC vs. CC) and 445 DEGs (CC vs. NC) were extracted based on the gene expression profile of GSE36758 and GSE8671, respectively. Total three PPI networks were constructed with DEGs in CC versus NC, SAC versus CC group, and DEGs in both two groups. Three modules were extracted from the PPI network of CC versus NC. Meanwhile, three modules were extracted from the network of DEGs in both two groups. Function enrichment analysis showed that DEGs involved in these modules were mainly associated with cellular activities. CONCLUSION: DEGs in modules of SAC and CRC were mainly involved in cellular activities pathways. The PPI networks and modules might contribute to the further study of pathogenesis for CRC and SAC based on the molecular level. PMID- 26881530 TI - Immunological subtypes analysis of Uygur diffuse large B-cell lymphoma in Xinjiang and their prognostic significance. AB - OBJECTIVE: This study aims to explore the application of Choi's typing method in the immunological typing of diffuse large B-cell lymphoma (DLBCL) in Xinjiang Autonomous Region and its prognostic significance. MATERIALS AND METHODS: Seventy eight cases of DLBCL tumor tissues from Xinjiang were collected to detect the expression of germinal center B (GCB) cell-expressed transcript-1, FOXP1, CD10, bcl-6, and MUM1 using an immunohistochemical method. Then, immunological typing was carried out using Choi's typing method, and the survival analysis was performed using Kaplan-Meier method. Cox proportional hazard model was used to analyze the prognostic factors. RESULTS: GCB-cell-like-DLBCL and non-GCB-DLBCL accounting for 29.5% (23/78) and 70.5% (55/78), respectively. The 3-year overall survival of GCB-DLBCL was 58%, significantly higher than that of non-GCB-DLBCL (39%, P < 0.05). Multivariate analysis showed that International Prognostic Index and immunological typing were two independent prognostic factors for Uygur patients with DLBCL. CONCLUSION: Non-GCB-DLBCL is the main type of DLBCL in Xinjiang and Choi's typing method can be a helpful indicator to determine the prognosis of the Uygur DLBCL in Xinjiang. PMID- 26881531 TI - Lenalidomide in relapsed refractory non-Hodgkin's lymphoma: An Indian perspective. AB - BACKGROUND: Lenalidomide an immunomodulatory agent has shown activity in relapsed/refractory lymphoma. This study was conducted to evaluate its efficacy and optimal dose in Indian patients with relapsed/refractory lymphoma who were unable or unwilling to undergo autologous hematopoietic stem cell transplant. MATERIALS AND METHODS: Patients received oral lenalidomide at 20 mg on days 1-21 every 28 days until disease progression or unacceptable toxicity. RESULTS: A total of 25 patients received lenalidomide at a starting dose of 20 mg. Majority of patients were diffuse large B-cell lymphoma (DLBCL). The overall response rate (ORR) was 48%, with 16% achieved complete remission (CR)/unconfirmed CR (CRu), 32% partial response (PR) and 16% stable disease (SD) Among patients with DLBCL the ORR was of 33.3%; with CR/CRu 20%, PR (13.3%), 20% had SD, progressive disease (PD) was seen in seven patients (46.6%). All follicular lymphoma patients responded to treatment, with CR in one patient and PR in other two. Among patients with mantle cell lymphoma, ORR was 75% with PR in (75%) and SD in 25%. One case of transformed lymphoma had a PR and peripheral T-cell lymphoma had no response to treatment. The median duration of response was 8.5 months, with a time to response of 3 months. Median progression free survival was not reached in responding patients. CONCLUSION: Lenalidomide is an effective treatment option in relapsed refractory non hodgkin's lymphoma. PMID- 26881532 TI - Preliminary dosimetry of (166)Ho-propylene di-amino tetra (methy1enephosphonicacid) for human based on biodistribution data in rats. AB - CONTEXT: Nowadays, radionuclides with high beta- particle energies such as (166)Ho are recommended for bone marrow ablation in patients with multiple myeloma. The addition of skeletal targeted radiotherapy to the patients can improve the response rate in phase I and II trials, with promising long-term survival data. AIMS: In this work, the absorbed dose to each organ of human for (166)Ho-propylene di-amino tetra methy1enephosphonicacid (PDTMP) was evaluated based on biodistribution studies in rats and was compared with (166)Ho tetraazacyclododecane tetramethylene-phosphonate (DOTMP) as the only clinically used Ho-166 bone marrow ablative agent. SETTINGS AND DESIGN: In this work, the accumulated activity in animals was extrapolated to the accumulated activity in humans by mass extrapolation method. The absorbed dose to each organ of human for (166)Ho-PDTMP was evaluated by medical internal radiation dose method. MATERIALS AND METHODS: In this study, 166 Ho-PDTMP complex was prepared successfully using an in-house synthesized PDTMP ligand and (166)HoCl 3. Radiochemical purity of (166)Ho-PDTMP was checked by instant thin layer chromatography (>99%). The biodistribution of (166)Ho-PDTMP in wild-type rats was checked in animal tissues up to 48 h. STATISTICAL ANALYSIS USED: All values were expressed as mean +/- standard deviation, and the data were compared using Student's t-test. Statistical significance was defined as P < 0.05. RESULTS: The highest absorbed dose for this complex is observed in red marrow with 0.691 mSv/MBq. (166)Ho-PDTMP demonstrated a higher red marrow: Non target organ uptake ratio compared to (166)Ho-DOTMP. CONCLUSIONS: The results showed that 166 Ho-PDTMP has considerable characteristics compared to (166)Ho-DOTMP and therefore can be a good candidate for bone marrow ablation. PMID- 26881533 TI - Nuclear anomalies in exfoliated buccal epithelial cells of petrol station attendants in Udaipur, Rajasthan. AB - AIM: The petroleum derivatives consist of a complex mixture of chemical compounds one among which is benzene. Petrol station workers who pump fuel to vehicles absorb the products of fuel fumes and the products of combustion. MATERIALS AND METHODS: To study the occupational exposure to petroleum derivatives such as benzene, exfoliated buccal cells from 40 petrol station attendants and 40 age matched control subjects were examined for micronuclei, binucleation, karyorrhexis and karyolysis frequency by using feulgen and Giemsa stains. Statistical evaluation was performed with ANOVA test. RESULTS: In the present study, inter-comparison of mean values for micronuclei, binucleation, karyorrhexis and karyolysis using Fuelgen stain between smokers of study and control group, as well as between smokers and non-smokers of study and control group revealed statistically highly significant results with P value 0.00002 and 0.0001 respectively. Whereas inter comparison between non-smokers of study and control group using Feulgen stain and inter comparison between smokers of study and control group, using Giemsa stain revealed statistically significant results with P value 0.0034 and 0.0004, respectively. CONCLUSION: This study revealed that the studied individuals belong to a risk group and should periodically undergo biological monitoring and proper care. PMID- 26881534 TI - Comparison of clinicopathological features of gastric carcinoma, between 2 times periods, at a single institute in China. AB - PURPOSES: This study aims to compare the clinicopathological features of gastric carcinoma between two different time periods, and to investigate the prognostic factors for gastric carcinoma. PATIENTS AND METHODS: One thousand sixteen consecutive gastric cancer patients were divided into two groups according to the operation date, period I (1994-1999) and period II (2000-2006). The clinicopathological features and prognosis were compared between the two periods. RESULTS: There were significant differences in the proportions of early gastric carcinoma, different tumor node metastasis (TNM) staged patients, specialized operation and adjuvant chemotherapy between the two periods. The 5-year survival rate after curative resection within period II, were significantly higher than those within period I. Stratification analysis revealed that the survival rates of the patients with curative resection, lymph node metastasis, advanced disease, different TNM stages, specialized operations, without adjuvant chemotherapy within period II, were significantly higher than those within period I. Multivariate regression analysis revealed that Borrmann type, histologic type, depth of invasion, lymph node metastasis, curative resection, adjuvant chemotherapy, and different time periods were independent prognostic factors for gastric carcinoma. CONCLUSIONS: The treatment efficacy of gastric carcinoma within the recent period improved highly when compared with that within the early period. It was the elevated diagnostic rate of early gastric cancer, standardized radical operation, and adjuvant chemotherapy that contributed to such improvement. PMID- 26881535 TI - Cardiac troponin-I, brain natriuretic peptide and endothelin-1 levels in a rat model of doxorubicin-induced cardiac injury. AB - BACKGROUND: Cardiotoxicity, during or after therapy, is the most serious side effect of doxorubicin (DXR). The risk of developing cardiac impairment increases concomitantly with an increase in the cumulative dose of DXR. AIM: The aim was to evaluate the levels of cardiac troponin-I (cTnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) in DXR induced cardiac injury. MATERIALS AND METHODS: Thirty-nine Wistar albino rats were divided into three groups; a control group and two-study groups that received low-dose DXR (LDD) and high-dose DXR (HDD) in a weekly schedule for reaching a cumulative dose. RESULTS: Serum cTnI level was significantly increased in both LDD and HDD-treated groups. Although serum BNP was not significantly increased either LDD or HDD-treated groups, ET-1 levels was significantly increased in only HDD-treated groups. Histopathologic injury was more evident in HDD-treated group. CONCLUSIONS: Serum cTnI was increased even in LDD and parallel to it low cardiac injury induced by DXR. In the low-dose group, BNP and ET-1 levels were not elevated significant as cTnI despite cardiac injury. Thus, cTnI may be a predictive marker in of DXR-induced cardiotoxicity. PMID- 26881536 TI - Construction and analysis of the regulatory network disturbed by the silenced Sp1 transcription factor in HeLa cells. AB - BACKGROUND: The objective of our study was to explore the characteristics of the regulatory network after siRNA-Sp1 (Specificity Protein 1) treatment in HeLa cells through the regulation network construction with bioinformatics methods. MATERIALS AND METHODS: Using GSE37935 datasets downloaded from Gene Expression Omnibus data, the differentially expressed genes (DEGs) were screened out by the limma package in R software. Combining the DEGs with the data from the microRNA (miRNA) databases and transcription factor databases, an integrated regulatory network was established with Cytoscape. Then the motifs in the network were examined by FANMOD. RESULTS: A total of 708 DEGs were screened, and a regulatory network consisting of 585 nodes and 1070 edges was constructed. By analyzing the two modules extracted from the network, we found that the most significant biological processes were cell cycle and apoptosis, some significant DEGs among them were CDKN1A, CUL5, and EGFR. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis discovered that DEGs, including EGFR, CDKN1A, RRM2B, and GADD45B, were significantly enriched in glioma pathway and p53 signaling pathway. CONCLUSION: While Sp1 was silenced by siRNA, the regulatory network in HeLa cells changed a lot. Genes related to cell cycle and apoptosis in the cell nucleus were dysregulated and the p53 signaling pathway was disturbed. PMID- 26881537 TI - Evaluation of stromal myofibroblasts in oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma--an immunohistochemical study. AB - BACKGROUND: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are the main potentially malignant disorders and oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral mucosa. Myofibroblasts (MFs) secrete numerous growth factors and inflammatory mediators that stimulate epithelial cell proliferation and play an important role in tumoral invasion and use a combination of different factors in the course of neoplastic growth and development. Hence the present study was undertaken to evaluate and compare the distribution of MFs using alpha smooth muscle actin (alpha-SMA) in OL, OSMF, and various histopathological grades OSCC. MATERIALS AND METHODS: Sixty formalin fixed paraffin-embedded tissue blocks consisting of histopathologically diagnosed cases of normal mucosa (n = 10), OL (n = 14) hyperkeratosis with various grades of dysplasia, OSMF (n = 11), and OSCC (n = 25) were subjected to immunohistochemistry using alpha-SMA antibody for detection of MFs. RESULTS: MFs were not detected in normal oral mucosa. On comparison of frequency of mean scores in OL, OSMF, and OSCC the values were 0.6 +/- 0.2 (0-2), 1.2 +/- 0.68 (1 2), and 2.6 +/- 1.34 (0-4), respectively. The results were statistically significant (P < 0.001). CONCLUSION: These findings are suggestive of role of MFs with the creation of a permissive environment for tumor invasion in OSCC. Hence the presence of MF is a prognostic marker and evaluation of the frequency in the stroma can be used as therapeutic targets. PMID- 26881538 TI - Prevalence of colorectal cancer in patients with ulcerative colitis: A retrospective, monocenter study in China. AB - BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is a serious complication of UC. Data on the clinical characteristics of patients in China are scarce. AIMS: We aimed to study the incidence, characteristics, treatment, and prognosis of CRC patients with a history of UC. MATERIALS AND METHODS: We identified patients with UC and followed them until the first occurrence of cancer, death, or emigration in a single study center in China. RESULTS: A total of 4 UC-associated CRC patients were identified among the 642 cases recorded from January 2000 to December 2012. The overall risk of cancer was 0.64%. The overall median duration of UC was 15.5 years (range 6-21 years) in patients with UC associated CRC. Of these patients, 75% (3/4) were at an advanced stage when they were diagnosed. Longer disease duration and extensive colitis were identified as risk factors for developing CRC, and 5-aminosalicylic acid and steroid therapies were not identified as protective factors against UC-associated CRC. CONCLUSIONS: Patients with UC are at an increased risk for CRC. However, the prevalence of CRC in China remains lower than that in the West. PMID- 26881539 TI - Chelerythrine delayed tumor growth and increased survival duration of Dalton's lymphoma bearing BALB/c H(2d) mice by activation of NK cells in vivo. AB - AIM: The aims of the present investigation were to evaluate the antitumor effect of chelerythrine (CHE) on in vivo growth and survival duration of BALB/c (H2d) mice bearing Dalton's lymphoma (DL) and enhanced function of tumor associated NK cells (TANK cells). MATERIALS AND METHODS: BALB/c (H2d) mice at 8-10 weeks of age of either sex were used. Increasing concentration of CHE (1.25, 2.5, and 5.0 mg/kg), staurosporine (0.625, 1.0, 1.5, and 2.0 mg/kg) and cyclophosphamide (25, 50, 100, and 200 mg/kg) were administered intraperitoneally and tumor regression and survival duration of tumor bearing host were determined, and thereafter expression of NKG2D and NKG2A on TANK cells were detected. RESULTS: Our results show that treatment with 2.5 mg/kg of CHE results in a significant reduction in mean tumor volume and increased survival duration of DL bearing BALB/c (H2d) mice when compared to control. Activating receptor NKG2D on TANK cells were observed upregulated in contrast to inhibitory receptor NKG2A. CONCLUSIONS: CHE reduced mean tumor volume and increased survival duration of DL bearing BALB/c (H2d) mice. Increased expression of activating receptor NKG2D on TANK cells results in recovery of immunosuppression during tumor progression. Therefore, CHE could be a potential anticancer therapeutic agent that may be used to replace chemo-radio therapy in future. PMID- 26881540 TI - A 36-year-old female with Krukenberg tumor from a colonic carcinoma. AB - Krukenberg tumor is bilateral ovarian carcinoma's metastasizing most commonly from a gastric primary followed by a colon. We report a case of 36-year-old female with bilateral ovarian mass diagnosed as Krukenberg with a work up for locating the primary site. In this case, we discuss widely the clinical aspects with histopathological features and literature review of Krukenberg tumor. PMID- 26881541 TI - Transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia as progression of myeloid neoplasm with platelet-derived growth factor beta rearrangement. AB - Myeloid neoplasms associated with platelet-derived growth factor b (PDGFRB) rearrangement usually keep only one morphologic type unless blast crisis. We describe a unique case of hematological features transformation from atypical chronic myeloid leukemia to chronic myelomonocytic leukemia, and imatinib showed no clinical therapeutic effects. The phenomenon indicates that different types of myeloid neoplasms associated with PDGFRB rearrangement can transform into one another with the progression of the disease, and to some extent, this transformation suggests the aggravation of disease. PMID- 26881542 TI - Gliosarcoma with leiomyomatous differentiation: A case report with an emphasis on histogenesis. AB - Gliosarcoma is an uncommon high-grade tumor which constitutes about 2% of all glioblastomas. These tumors have the histological hallmark of a biphasic pattern of high-grade glial and sarcomatous components. The histogenesis of these tumors is controversial. We report a case of primary gliosarcoma in an adult male with leiomyomatous differentiation and discuss the histogenesis as it appears in our case. Primary gliosarcomas of the brain are clinically challenging with a poor clinical outcome. PMID- 26881543 TI - Sunitinib treatment of metastatic renal cell carcinoma in von Hippel-Lindau disease. AB - Von Hippel-Lindau disease (VHL) is a major heritable renal cell cancer (RCC) syndrome. 24-45% of VHL patients have a cumulative risk to develop RCC. The management of VHL has changed significantly as clinicians have learned how to best balance the risk of cancer dissemination while minimizing renal morbidity. Despite the improving management of this disease, there are no evidence-based guidelines of the treatment of localized and advanced RCC in VHL. Here, we describe a 39-year-old patient with VHL disease who developed metastatic RCC and received sunitinib with complete remission. PMID- 26881544 TI - Primary extramedullary plasmacytoma of ovary: Report of a rare neoplasm. AB - Primary extramedullary plasmacytoma is a rare plasma cell neoplasm. Extramedullary plasmacytomas are most commonly found in head and neck region, but it can occur at other sites occasionally. Involvement of ovary by this tumor is exceedingly rare. Here, we report a case of primary ovarian plasmacytoma in a 47 year-old woman. The patient presented with a lower abdominal pain and a left ovarian mass (12 cm * 10 cm) was detected during the ultrasonographic examination. The patient underwent hysterectomy with bilateral salpingo oophorectomy. Subsequent histopathologic, immunohistochemistry, bone marrow examination, and other relevant examinations established the diagnosis of primary ovarian plasmacytoma. The patient did not receive the postoperative chemotherapy and 6 months follow-up was uneventful. PMID- 26881545 TI - Juan-Ron fever: A rare case report. AB - Juan-Ron fever named after Juan Rosai and Ronald Dorfman is the fever associated with Rosai-Dorfman disease also known as sinus histiocytosis with massive lymphadenopathy (SHML). It is a rare disorder of unknown etiology that is characterized by abundant macrophages in the lymph nodes throughout the body. Usually patient presents with painless lymphadenopathy. We present a case of a 45 year-old male who presented to us with bilateral cervical lymphadenopathy and fever, later on diagnosed to have SHML. PMID- 26881546 TI - Primary clear cell carcinoma of the nasopharynx. AB - A 22-year-old female with epistaxis and nose block had a pink, smooth, mucosa covered lesion occupying the nasopharynx. The histopathology and immunohistochemistry of the lesion confirmed the diagnosis of clear cell carcinoma (CCC). Detailed evaluation ruled out a primary tumor elsewhere in the body. After complete excision of the tumor patient received radiotherapy (60 Gray in 30 fractions over 6 weeks). Patient is recurrence free on her 3-year follow up. Primary CCC of the head and neck is rare. In the past 30 years, less than 100 cases have been reported in English literature. Out of these, only nine cases had nasopharyngeal origin. The literature review of those cases along with our case report suggest that complete excision of nasopharyngeal CCC along with radiotherapy leads to prolonged recurrence free interval. However, extensive tumors of nasopharynx exhibit poor prognosis with repeated local recurrences. PMID- 26881547 TI - Acinic cell carcinoma of buccal mucosa: An unusual presentation. AB - Acinic cell carcinoma (ACC) is a rare epithelial malignant neoplasm of salivary glands affecting predominantly the female population. Unusual occurrences of this neoplasm are reported in hard palate, maxillary sinuses, lip, etc. [1] We report one such case where a submandibular swelling that is provisionally diagnosed as pleomorphic adenoma due to its clinical and radiological findings, turned out to be ACC on histopathological evaluation. PMID- 26881548 TI - Adult Wilms' tumor: A case report with review of literature. AB - Wilms' tumor presents a diagnostic problem due to its rare occurrence in adults. Most of the cases of adult Wilms' tumor are diagnosed unexpectedly following nephrectomy for renal cell carcinoma. We are reporting herein a rare case of Adult Wilms' tumor of kidney with triphasic histology and distant metastasis to lung. PMID- 26881549 TI - Aggressive angiomyxoma of vulva in a 13-year-old female. AB - Aggressive angiomyxoma is a rare mesenchymal neoplasm that typically affects females of reproductive age. It involves preferentially pelvic and perineal regions and was first described by Steeper and Rosai in 1983. Peak age of incidence for this tumor is in the fourth decade with very few cases reported in young girls. We present a case of this rare tumor in a 13-year-old female. PMID- 26881550 TI - Mesothelioma with superior vena cava obstruction in young female following short latency of asbestos exposure. AB - An 18 years female was admitted with right-sided chest pain, dry cough, and low grade fever and weight loss for last 1 month. On examination, patient had features of superior vena cava (SVC) syndrome with right-sided pleural effusion. Chest X-ray showed mediastinal widening with nonhomogenous opacity mainly in the periphery of right upper and mid zone with right-sided pleural effusion. Ultrasonography thorax confirmed mild pleural effusion. Pleural fluid analysis showed lymphocytic, exudative, low adenosine deaminase with negative for Pap smear. Contrast-enhanced computed tomography (CT) thorax revealed large extensive nodular soft tissue lesion along right mediastinum as well as costal pleura, with enlarged pretracheal lymphadenopathy and SVC obstruction. CT guided Tru-cut biopsy report came as malignant epithelial tumor with polygonal shape, abundant eosinophilic cytoplasm and nuclei with prominent nucleoli suggestive of mesothelioma of epithelioid type. The tumor cell expressed calretinin, WT-1, and immunonegative for thyroid transcription factor-1. PMID- 26881551 TI - A rare case of primary anaplastic large cell lymphoma of the central nervous system. AB - Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin's lymphoma, confined to the central nervous system (CNS) and is usually seen in immunocompromised patients. The vast majority of cases are of the B-cell type and T-cell PCNSL is rare. Here, we report an 18-year-old male who presented with fever, headache, and history of seizures. On evaluation, he was found to have a left parieto-occipital mass which was completely excised. Histopathology was suggestive of a T-cell neoplasm and immunohistochemistry showed tumor cells positive for leukocyte common antigen, anaplastic lymphoma kinase (ALK), CD30, and CD4 which confirmed the diagnosis of ALK-positive anaplastic large cell PCNSL. There was no evidence of disease outside the CNS. He was started on the DeAngelis protocol for PCNSL. To the best of our knowledge, only 27 cases of anaplastic large cell PCNSL have been previously reported in literature. PMID- 26881552 TI - Enriched vascularity in ameloblastomas, an indeterminate entity: Report of two cases. AB - Vascularity is a highly essential element that is required for the growth, development, and functioning of the body and variations in it can cause pathologies. It is one of the prime features of a proliferating lesion, where it aids in the growth of the lesion through its nutrition supply. Highly increased vascularity in a disease can itself affect the prognosis of the lesion, and in malignancies, it can induce tumor seeding and secondaries. Most of the pathologies including tumors, related to blood vessels, and vascularity are well established. There are some conditions, wherein altered vascularity is one of the prime components along with other diagnostic components of an established disease. In such cases, these lesions are diagnosed with special names, with varying biological behavior and prognosis in comparison to that of established entity. However, there still are few similar conditions whose nature is uncertain due to the rarity of the lesion and the insufficient scientific evidence which eludes the diagnostician. Here is the report of two cases of ameloblastoma, an established entity, with significant vascularity whose nature is indeterminate. PMID- 26881553 TI - T-cell prolymphocytic leukemia presenting with leukemic serous effusion in a prostate cancer patient. AB - T-cell prolymphocytic leukemia (T-PLL) is highly aggressive mature postthymic lymphoproliferative disorder, which is characterized by several clinical features. Leukemic prolymphocytes are found in the peripheral blood, bone marrow, lymph nodes, spleen, liver, and sometimes skin. T-PLL and solid tumor coincidence was reported by only four previous cases. Solid tumor components included breast cancer, classic Kaposi sarcoma, gastric cancer, and lung cancer in those cases. We report the first case of T-PLL, an extremely rare disease, presented with serous effusion in an elderly prostate cancer patient in literature. PMID- 26881554 TI - A rare coexistence--Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature. AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS)-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies. PMID- 26881555 TI - Choroidal melanoma of left eye with very early liver metastasis. AB - Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). The liver is a frequent site for metastasis in patients with uveal melanoma. The interval between the diagnosis of the uveal melanoma and the diagnosis of the metastatic lesion can vary. Despite therapy, the median survival of those with liver metastasis is 5-7 months. We report here a rare case of choroidal melanoma in a 45-year-old male smoker presented with liver metastasis within just 8 months after completion of initial treatments consists of enucleation of eye and 3 Dimensional conformal radiation therapy (3D-CRT). The metastasis is an incidental finding on imaging after having some vague symptoms. This type of very early metastasis after completing initial treatment is very rare and proves the aggressiveness of the disease. PMID- 26881556 TI - A rare case: Hallucination associated with pazopanib. AB - Diarrhea, hyperglycemia, anemia, depigmentation of the hair, and rash are common side effects of tyrosine kinase inhibitors. Neurological side effect like hallucination due to pazopanib is exceptionally rare in literature cases. Herein, we reported a case of hallucination related to pazopanib in a patient with renal cell carcinoma. A 47-year-old male patient with renal cell carcinoma developed repetitive hallucinations on the following days of pazopanib initiation. There was no other significant finding in the differential diagnosis of hallucination. Neurological symptoms disappeared after termination of pazopanib. We aimed to emphasize that neurological side effect like hallucination may rarely occur during the treatment of pazopanib and take note that physicians should be aware of this infrequent side effect in the patients treated with pazopanib. PMID- 26881557 TI - Malignant extra-renal rhabdoid tumor with unusual presentation: A report of two cases. AB - Malignant extra-renal rhabdoid tumor (MERT) is a rare highly aggressive tumor that occurs in young children with the very poor clinical outcome. The tumor is characterized by a diffuse proliferation of "rhabdoid cells," which are round or polygonal with eccentric nuclei, prominent nucleoli, and glassy eosinophilic cytoplasm containing hyaline-like inclusion bodies. However, rhabdoid cells are also seen in certain other soft tissue sarcomas such as proximal-type epithelioid sarcoma, rarely synovial sarcoma, and extra-skeletal myxoid chondrosarcoma. Because of its poor prognosis and histomorphological similarities with other soft tissue tumors, an accurate diagnosis is required using a wide immunohistochemical panel. Very few cases of MERT have been reported in the literature and to our knowledge none in the supra-glottis area. Due to the rarity and poor outcome of this tumor, we are reporting two cases of MERT. PMID- 26881558 TI - Cystic adenomatoid tumor of the uterus. AB - We present a case of a cystic adenomatoid tumor in a 40-year-old woman. The tumor was an intramural multicystic mass, histologically similar to a multicystic mesothelioma. Cystic adenomatoid tumors of the uterus are extremely rare. They present with a wide differential diagnosis in radiology. The tumors are known to be benign and awareness of this rare entity is the key to its diagnosis for a pathologist. PMID- 26881559 TI - A giant vagal schwannoma with unusual extension from skull base to the mediastinum. AB - Cervical vagal schwannoma is an extremely rare neoplasm. Middle aged people are usually affected. These tumors usually present as asymptomatic masses. These tumors are almost always benign. Preoperative diagnosis of these lesions is important due to the morbidity associated with its excision. Preoperative tissue diagnosis is not accurate. The imaging modality can be done to assess the extent and for planning the treatment. Surgical excision with preservation of neural origin is the treatment option. Giant vagal schwannomas are extremely rare. Only one case has been reported in the literature till date. There has no reported case of extensive vagal schwannoma from skull base to the mediastinum. Here, we describe the asymptomatic presentation of an unusual appearing giant cervical vagal schwannoma with an extension from skull base to the mediastinum. PMID- 26881560 TI - Complete response of a recurrent-metastatic liposarcoma with dedifferentiated histological features following the administration of trabectedin and review of literature. AB - The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved. PMID- 26881561 TI - Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations. AB - Primary prostatic lymphomas are extremely unusual neoplasms. Their rarity and nonspecific symptomatology at presentation usually prompt a clinical diagnosis of benign prostatic hyperplasia or chronic prostatitis, leading to significant delay in diagnosis. Clinical examination, serum prostate-specific antigen levels, and transrectal ultrasonography (TRUS) are not of much utility in differential diagnosis, and histological examination is the gold standard. We report two cases of primary non-Hodgkin lymphoma of prostate, diffuse large B-cell type, diagnosed on TRUS-guided prostatic biopsies. Correct diagnosis is of crucial importance as the therapeutic strategy for lymphoma is radically different from that for carcinoma, and early detection of prostatic lymphoma can be potentially curative. Thus, knowledge of this rare entity, inclusion in differential diagnosis of lower urinary tract obstruction, and application of an appropriate immunohistochemical panel are essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery. PMID- 26881562 TI - Breast carcinoma with numerous large "thanatosomes". AB - Intracytoplasmic and stromal eosinophilic hyaline globules (HGs) have been observed in various neoplastic and nonneoplastic conditions. Thanatosomes are also such HGs seen invariably associated with increased apoptosis and may contain nuclear fragments, occasionally observed in high-grade tumors. We are reporting a case of high-grade breast carcinoma with this striking morphological feature. Their probable nature, pathogenesis, and significance are discussed with review of literature. PMID- 26881563 TI - A rare case of cisplatin-induced acute myocardial infarction in a patient receiving chemoradiation for lung cancer. AB - We present this unusual case of cisplatin-induced acute myocardial infarction in a patient with no organic coronary artery disease (CAD), receiving chemoradiation for small cell lung cancer. Patient developed symptoms of acute coronary syndrome after receiving two cycles of cisplatin and etoposide. The possible mechanism of vasospasm induced by cisplatin, in the background of thoracic radiation and hypomagnesemia, is discussed in this case report. PMID- 26881564 TI - Papillary thyroid microcarcinoma in Graves' disease presenting as a cystic neck mass. AB - The presentation of papillary thyroid microcarcinoma (PTMC) as a solitary cystic neck mass is uncommon. Additionally, its association with Graves' disease is very rare. We report a case of occult PTMC, who presented with a cystic neck mass in the background of Graves' disease without any goiter. Imaging like ultrasound of neck, single photon emission computed tomography-CT (SPECT-CT), and technetium scan failed to detect any lesion in the thyroid, which was picked up only by the contrast-enhanced computed tomography (CECT) of neck. The patient underwent total thyroidectomy with right modified lymph node dissection. Our case highlights the presentation of metastatic PTMC as a differential diagnosis of a cystic neck mass even in a patient with Graves' disease without any thyroid enlargement. PMID- 26881565 TI - Giant cell rich osteosarcoma of the cuneiforms. AB - Osteosarcoma is the commonest primary malignant bone tumor in children and adolescents. Giant cell rich osteosarcoma is a rare subtype of conventional osteosarcoma. Osteosarcomas commonly involve the metaphysis and meta-diaphysis of long bones. We report a 19-year-old girl with giant cell rich osteosarcoma of the medial and intermediate cuneiform bones. Even though, giant cell rich osteosarcoma is frequently mistaken for osteoclastoma of the bone; age of onset, location of lesion, radiological features, and histological characteristics on a high power field helps to differentiate the two conditions. Appropriate and early diagnosis of this variant possibly averts severe morbidity and mortality to the patient. Nonmetastatic osteosarcomas in the foot have better prognosis and are amenable to limb salvage surgeries. PMID- 26881566 TI - Imatinib mesylate induced erythroderma: A rare case series. AB - Imatinib is a tyrosine kinase inhibitor approved as a first line treatment for chronic myeloid leukemia and gastrointestinal stromal tumors. Usually the drug is well-tolerated with hematological adverse effects being most commonly seen. Dermatological side effects are seen in 9.5-69% of patients on imatinib; majority of which are minor and self-limiting. We, hereby, report a case series of erythroderma occurring secondary to imatinib in two patients with chronic myeloid leukemia. Both the patients improved upon the discontinuation of the drug. The literature review revealed only six probable cases of erythroderma due to imatinib. So, this case series is being reported for the rarity of this adverse effect of imatinib. PMID- 26881567 TI - Uterine malignant mixed Mullerian tumor camouflaging as pelvic sarcoma. AB - Malignant mixed Mullerian tumors (MMMTs) of the uterus are rare, aggressive tumors that present at an advanced stage and are associated with poor prognosis. They arise as a result of divergent carcinomatous and mesenchymal differentiation of tumor stem cells. Rarely one of the components may predominate contributing to diagnostic confusion. We present a rare case of uterine MMMT arising in endometrial adenocarcinoma, camouflaging as pelvic sarcoma with a major sarcomatous component. This case report highlights the importance of thorough tissue sampling and the role of immunohistochemistry (IHC) in arriving at an accurate diagnosis. This case also demonstrates the conversion theory of histogenesis of MMMTs. PMID- 26881568 TI - Extragonadal yolk sac tumor of the head and neck region: A report of two cases. AB - Extragonadal germ cell tumors (EGCTs) are rare and head and neck is a rarer primary site with most tumors being benign exhibiting teratoma as the leading histologic type. Yolk sac tumor (YST) is relatively uncommon in this location; most commonly described in association with a teratoma and rarely solo. We report two male children, aged 1 year 7 months and 3 years 5 months, with YST involving the head and neck region. PMID- 26881569 TI - Neoadjuvant chemotherapy in advanced sinonasal teratocarcinosarcoma with intracranial extension: Report of two cases with literature review. AB - Sinonasal teratocarcinosarcoma (SNTCS) is a highly aggressive rare tumor of the nasal cavity. Surgery followed by concurrent chemoradiation is the mainstay of treatment in SNTCS. However, intracranial extension may complicate surgical resection, with difficulty in achieving R0 resection. Here we present two cases of SNTCS with intracranial extension; both patients were seen in skull base clinic of our hospital and deemed unsuitable for surgery. These patients then were offered neoadjuvant chemotherapy (NACT), both patients had a partial response with cisplatin and etoposide protocol; subsequently they underwent R0 resection (no macroscopic residual tumor at surgery with all margins were negative for tumor on microscopy). The present cases highlight the fact that NACT with cisplatin and etoposide protocol may be considered in technically unresectable SNTCS. PMID- 26881570 TI - Acute renal failure secondary to ingestion of alternative medication in a patient with breast cancer. AB - Complementary and alternative medicine (CAM) use among cancer patients is widely prevalent and often underreported. Advanced stage of disease is significantly associated with CAM use. The concurrent use of alternative medicines and chemotherapy drugs has the potential to lead to toxicities as well as altered therapeutic activity due to unknown interactions. We report a case of early breast cancer who presented to us with non-oliguric acute renal failure related concurrent use of Ayurvedic medicines and adjuvant anthracycline based. PMID- 26881571 TI - Granulocytic sarcoma of the dorsal spine in an aleukemic patient. AB - The spine is an uncommon location for granulocytic sarcoma that is an extramedullary deposit of malignant myeloid cells. Very few cases are reported in literature as occurring in aleukemic patients. Due to histopathological similarity with lymphoma, Ewing's sarcoma, and multiple myeloma, the diagnosis is often missed. We describe a 22-year-old man presented with worsening dorsal compressive myelopathy in whose treatment was started after initial diagnosis of a lymphoma and who has had no leukemic conversion even after 2 years. PMID- 26881572 TI - A rare case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a patient of acute lymphocytic leukemia. AB - Neurotoxic reactions of chemotherapy occur frequently and are often dose limiting side effects of chemotherapy. It is important to differentiate these various nonneoplastic effects from metastases, or sometimes even from each other, since the therapeutic approach differs accordingly. To arrive at a definitive and comprehensive diagnosis, the radiologist should integrate imaging findings, clinical signs, and laboratory results together. Here we present a unique case of chemotherapy induced reversible cerebral vasoconstriction syndrome in a 13-year old patient of acute lymphoblastic leukemia. PMID- 26881573 TI - Primary Ewing's sarcoma of the squamous part of temporal bone in a young girl treated with adjuvant volumetric arc therapy. AB - Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumors usually arise in the long bones of children and young adults. Primary ES of the cranium is unusual. Treatment involves multi-modality therapy incorporating surgery, radiotherapy and chemotherapy; outcomes are similar to those arising from long bones. We report a case of Primary ES of the squamous part of temporal bone with intracranial extension in a 9-year-old girl who was treated with surgery, chemotherapy followed by adjuvant radiotherapy by volumetric arc therapy. Post 1 year of treatment the girl is performing well in her classes. PMID- 26881574 TI - Experience of bevacizumab in a patient with colorectal cancer after renal transplantation. AB - Bevacizumab is a drug that is widely used for the first-line treatment of metastatic colorectal cancer (mCRC). Bevacizumab neutralizes vascular endothelial growth factor and can lead to proteinuria and renal damage. In this case, experience on full dose short-time treatment of bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic renal failure has been shared. The patients were diagnosed with mCRC 7 months ago. The patient had multiple liver metastases at the time of the diagnosis. He had a history of renal transplantation 2 years ago because of renal failure, and he had been under immunosuppressive treatment for this reason. 5-fluorouracil-leucovorin-irinotecan -bevacizumab regimen was begun for the treatment of mCRC. The dose of bevacizumab was 5 mg/kg/day for 14 days. There was 2.5 g/day of proteinuria at the start of the treatment. However, renal dysfunction progressed, and proteinuria increased to 4 g/day in the 3rd month of treatment. In this case, the experience of using bevacizumab in a patient under immunosuppressive treatment for renal transplantation with chronic failure has been presented. PMID- 26881575 TI - Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report. AB - Angiosarcomas are rare tumors that predominantly affect adults. Hepatic angiosarcoma in a child is extremely rare and associated with a poor prognosis. Herein, we report the pathologic features of a hepatic angiosarcoma developing in a 31/2-year-old child who had been earlier diagnosed and was being treated for hepatic hemangioendothelioma. PMID- 26881576 TI - Oxaliplatin-induced posterior reversible encephalopathy syndrome with isolated involvement of pons. AB - Isolated pontine lesion can be caused by the posterior reversible encephalopathy syndrome (PRES). It does occur in the normotensive patient who is treated with oxaliplatin. We reported a case of 81-year-old Chinese man with metastatic colorectal carcinoma who was initially treated with capecitabine. No significant adverse effects were noted. However, the response to the treatment was poor. Subsequently, Xelox was given. He developed transient altered mental status. Oxaliplatin was thought to be the causative agent and was withheld. Magnetic resonance imaging brain revealed vasogenic edema in the pons that was reversible after 2 weeks, as well as complete resolution of clinical symptoms. Early identification of the reversible cause of isolated pontine lesion, such as chemo, triggered PRES is crucial to facilitate prompt treatment by removing the offending agent or reducing the dose. PMID- 26881577 TI - Atypical extraventricular neurocytoma:A report of two cases. AB - Central neurocytomas are tumors with neuronal differentiation, generally arising in the lateral ventricles in the region of foramen of Monro. Whenever these tumors arise in the brain parenchyma they are called "extraventricular neurocytomas". We present two unusual cases of extraventricular atypical neurocytomas at uncommon locations with a very high Ki-67 index. The WHO grading of this tumor is yet to be answered. PMID- 26881578 TI - A rare case of chronic myeloid leukemia with acquired von Willebrand disease presenting as subdural hematoma. AB - We report a case of a 32-year-old lady with chronic myeloid leukemia (CML) on Imatinib for the past four years and in complete clinical, hematological and molecular remission who presented to us with sudden onset of headache, vomiting and diplopia following self discontinuation of Imatinib for a month. Investigations were suggestive of chronic phase CML (CML-CP) with massive thrombocytosis and magnetic resonance imaging (MRI) of the brain revealed subdural hematoma. Coagulation studies confirmed the diagnosis of Acquired von Willebrand disease (AvWD) 2A because of thrombocytosis. The patient also tested positive for mutation T315I in bcr-abl gene. Treatment of the patient with high dose of Imatinib and hydroxyurea led to normalisation of platelet counts, reversal of coagulation defect and subsidence of symptoms. The present case highlights the importance of diagnosis of AvWD to determine the cause of bleeding in CML and distinguish it from Imatinib-induced bleeding, as prompt treatment with Imatinib can achieve reversal of the condition. PMID- 26881579 TI - Carcinosarcoma of ovary with its various immunohistochemical expression: Report of a rare case. AB - Ovarian carcinosarcoma is an extremely rare tumor with an incidence of <2%. A report of such a rare case in a 40-year-old multiparous woman is being presented here. The patient complained of abdominal pain and distension. Abdominal computed tomography revealed a variegated mass in the right adnexal region. The CA-125 level was 1635 U/ml. The patient underwent laparotomy and the tumor was removed. Microscopic examination of the tumor showed presence of both carcinomatous and sarcomatous elements. Immunohistochemical analysis revealed that the carcinomatous component was positive for cytokeratin and estrogen receptor and negative for progesterone receptor. The sarcomatous component was positive for vimentin. Ki-67 was positive in 60% cells. A final diagnosis of ovarian carcinosarcoma was rendered. This case is significant owing to extreme rarity of the tumor. Records of similar cases must be maintained for future reference with regard to impact of treatment protocol followed on prognosis. PMID- 26881580 TI - A rare occurrence of basal cell adenoma of palate: A case report with comprehensive immunohistochemical analysis. AB - Basal cell adenoma (BCA) of the salivary glands is an uncommon type of monomorphic adenoma which constitutes 1% of all salivary gland tumors. It most commonly involves parotid gland, while it rarely occurs in minor salivary glands. Upper lip, buccal mucosa, and lower lip are the common intraoral sites; whereas, palate being the rarest one. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, basaloid squamous cell carcinoma, and adenoid cystic carcinoma (AdCC) is mandatory. Considering the rarity of this lesion and histologic paradox regarding its diagnosis, we report a case of BCA of palate with emphasis on need of comprehensive immunohistochemical (IHC) analysis. PMID- 26881581 TI - Malignant peripheral nerve sheath tumor of the uterine corpus presenting as a huge abdominal neoplasm. AB - A 45-year-old P3L3, referred to us with abdominopelvic mass for further management. Vaginal examination was suggestive of uterine mass. Magnetic resonance imaging. (MRI) of abdomen.pelvis disclosed a uterine mass with equivocal invasion of the fat plane with the sigmoid colon. Coelomic antigen. (CA) 125 was 120.2 U/ml. (normal range, 0-35 U/ml). On exploratory laparotomy entire pelvic cavity was filled with a mass that was seen arising from the uterus and involving the sigmoid colon. Hence, a total abdominal hysterectomy with bilateral salpingo-oopphorectomy. (TAH BSO) was performed, along with resection anastomosis of the rectosigmoid and excision of omental and pelvic peritoneal nodules. Histopathology and immunohistochemical analysis, including S100-P positivity confirmed diagnosis of a malignant peripheral nerve sheath tumor. (MPNST), with tumor deposits in the right parametrium, omentum, sigmoid colon, and pelvic peritoneum. This case is presented in view of its rarity and associated diagnostic and therapeutic implications. PMID- 26881582 TI - An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast. AB - Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 * 2 * 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis. PMID- 26881583 TI - Liposarcoma of the maxillary antrum: A case report. AB - Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma. (ALT/WDL) is a soft tissue sarcoma of intermediate malignant behavior, which most frequently affects the retroperitoneum and lower extremities. Liposarcomas of head and neck are rare, representing only 2-8% of all sarcomas in this region. The majority of liposarcomas occur in middle-aged adults; however, very uncommonly cases have been reported in infancy and early childhood. We report a case of a 14-year-old girl diagnosed as ALT/WDL of the maxillary antrum. PMID- 26881584 TI - A rare case of carcinosarcoma of breast: Coexistence of mucinous carcinoma and malignant fibrous histiocytoma. AB - Carcinosarcoma (CS) of breast is a rare disease. Published reports provided little consensus about its clinical characteristics and optimal treatment protocols. Here we present a patient with CS of breast (mucinous carcinoma and malignant fibrous histiocytoma) and review related literature. Combined modality treatment (CMT) brings at least 2 year disease-free survival (DFS). Our case highlights the possibility of breast CS and helps to expand our understanding of this distinct breast malignancy. PMID- 26881585 TI - Interleukin-11-induced capillary leak syndrome companied with abdominal chylous leakage in primary sigmoid carcinoma patients with thrombocytopenia. AB - Capillary leak syndrome (CLS) is a rare condition characterized by generalized edema and hypotension. Interleukin-11 (IL-11) is a therapeutic agent for the treatment of thrombocytopenia. The relationship between IL-11 and CLS has rarely been reported, especially in patients with colorectal cancer. We describe a case with sigmoid cancer treated with IL-11 after chemotherapy. After 5 days of IL-11 therapy, the patient felt tachypnea, muscular pain and fullness of the abdomen. Chest X-ray indicated increased bronchovascular shadows, and abdominal ultrasound indicated moderate ascites. IL-11 was then discontinued, fluid resuscitation was performed, and fresh frozen plasma and packed red blood cells were transfused. On the fourth day, synchronous chylous leakage was detected. Low fat diet, nutritional support, and somatostatin was administered. The patient recovered 2 weeks later. Although rare, CLS could be a severe side effect after the administration of IL-11. The aim of treatment is to stabilize the vital parameters. PMID- 26881586 TI - Krukenberg tumor presenting with amenorrhea as the sole initial symptom: Case report and review of the literature. AB - Krukenberg tumor (KT), mostly originates from gastric cancer, is the metastatic tumor of ovaries accounting for 1-2% of all ovarian cancer. Common presenting symptoms include abdominal pain, distension, and ascites. Rests of the patients have non-specific gastrointestinal symptoms including dyspepsia, weight loss, nausea and vomiting. Gynecologic symptoms such as virilization, menstrual bleeding or irregularity and amenorrhea are much less frequent in the literature cases. Here, we present an unusual case of KT presented with amenorrhea as the sole initial symptom. PMID- 26881587 TI - Squamous cell carcinoma arising in mature cystic teratoma with sigmoid invasion. AB - Malignant transformation in a mature cystic teratoma (MCT) is rare occurring in 1.8% out of 8000 cases of MCT. The most common histological types are squamous cell carcinoma (SCC) followed by adenocarcinoma and melanoma. Clinically, these tumors are usually asymptomatic but may be discovered accidentally during gynecologic examination due to mass effect. We present cytology and histology correlation of a rare case of SCC arising in a dermoid cyst with metastasis to sigmoid. PMID- 26881588 TI - Erysipeloid rash: A rare adverse event induced by gemcitabine. AB - Some rare cases of erysipelas-like or pseudocellulitis have been reported in relation to gemcitabine. This rare adverse event is more frequent in the presence of edema. Here, we report a case of pseudocellulitis after adjuvant treatment for pancreatic cancer. Oncologists should be aware of this infrequent and non-well understood adverse event. They should be especially careful when administering gemcitabine in the presence of lymphedema. PMID- 26881589 TI - An unusual case of cervical lipoblastoma with review of literature. AB - Lipoblastoma is a rare, benign, soft tissue neoplasm most commonly seen in children less than 3 years. It is usually seen on the trunk and on the limbs and rarely in the head and neck. In our case, a child of age 1 year and 3 months presented with a swelling over the nape of the neck. The swelling had rapidly increased in size and was associated with difficulty in neck movements. Intraoperatively it was found to have very minimal adhesions to the underlying muscles of neck. Histopathological examination confirmed it to be a lipoblastoma. The swelling was removed by wide excision, and there was no postoperative complication. PMID- 26881590 TI - Burkitt's lymphoma of the humerus. AB - Burkitt's lymphoma is an uncommon form of non-Hodgkin's lymphoma (NHL) in adults and represents < 5% of NHL adults. Burkitt's lymphoma involving primarily the appendicular skeleton is rarely described. We present the case of a young man with primary Burkitt's lymphoma involving the humerus as the only site of disease. He received R hyper CVAD and local irradiation and is in complete remission at 24 months. PMID- 26881591 TI - Unusual presentation of melanoma of unknown primary origin: A case report and review of literature. AB - Malignant melanomas often present with metastasis to regional lymph nodes. Patients are also known to present with metastatic nodes in the absence of a known primary. However metastatic melanoma involving the stomach is rare in the scenario of an unknown primary lesion. We present a case of a 41-year-old lady who was treated for nodal disease in the right axilla 8. months earlier with an unknown primary. She later presented to us with a recurrent right axillary swelling and on evaluation was found to also have a nodular deposit on the greater curvature of the stomach. Histopathology of the deposit in conjunction with immunohistochemical markers S.100P, Melan-A and HMB-45, confirmed the diagnosis of malignant melanoma. The patient underwent surgical excision of both lesions and is now on regular follow-up. PMID- 26881592 TI - Pleomorphic adenoma involving minor salivary glands of upper lip: A rare phenomenon. AB - Pleomorphic adenoma is the most common benign tumor of salivary glands, usually occurs in major salivary glands (mostly in parotid gland). It also affects the minor salivary glands present in the oral cavity. Most of the time it occurs in postero-lateral part of palate, but the involvement of upper lip is rare. The present report describes a case of 55-year-old male with asymptomatic firm nodular swelling of upper lip which was later diagnosed as pleomorphic adenoma. PMID- 26881593 TI - Primary juxtacortical chondrosarcoma of mandibular symphysis: Unique and rare case report. AB - Juxtacortical chondrosarcoma (JC) is a rare, malignant, cartilage-forming tumor arising from the external bone surface. It mainly involves long bones and very rarely involves maxillofacial skeleton. Chondrosarcoma in general accounts for about 10-20% of all bone neoplasm, of which only 1-3% is involved in maxillofacial skeleton. So far only two cases of JC have been reported in mandible. In this article we report a rare case of JC in a 49-year-old male primarily involving symphysis of mandible. This is the third case of JC in mandible and first of its kind to be reported in mandibular symphysis region is concerned. Literature relevant to its clinical, radiological features, and prognosis is analyzed. PMID- 26881594 TI - A case of gastric cancer with liver metastases had a complete response with cisplatin and capecitabine as third-line chemotherapy. AB - Advanced gastric cancer has a poor prognosis, and only chemotherapy improves survival. Further chemotherapy after progression is controversial. Eastern Cooperative Oncology Group performance status is an important indicator for new chemotherapy decision. Complete response (CR) after recurrent disease is very rare, but could occur in some cases with chemotherapy. The 68-year-old male received chemotherapy for metastatic gastric adenocarcinoma. He received epirubicin, cisplatin and fluorouracil in the first line, capecitabine in the second line and cisplatin-capecitabine in the third line. CR was observed after third-line chemotherapy with four courses. Mediastinal and abdominal metastases were completely resolved. We decided to report this patient because it is very unusual to achieve CR in a patient in whom the best supportive care might be reasonable. PMID- 26881595 TI - Pulmonary plasmacytoma with endobronchial extension: A rare presentation of solitary extramedullary plasmacytoma: A case report and brief review of literature. AB - Extramedullary plasmacytoma is the malignant proliferation of single clone of plasma cells arising outside the bone marrow. Solitary extramedullary plasmacytoma (SEP) are solitary lesion mostly located in upper respiratory tract and nasopharynx. Involvement of lower respiratory tract is rarely seen in case of SEP. Here, we report a rare case of pulmonary plasmacytoma in a 50-year-old male presenting as left lower lobe lung mass with endobronchial extension. Subsequent investigations, histological and immunohistochemical examination of tumor confirmed the diagnosis of plasmacytoma. Work-up for the multiple myeloma came out to be negative, thus confirming the diagnosis of SEP. Pulmonary plasmacytoma, a rare presentation of extramedullary plasmacytoma should be kept in mind by dealing with the patients of lung mass and endobronchial extension. PMID- 26881596 TI - Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma. AB - The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks. PMID- 26881597 TI - Contralateral contiguous tuberculous lymphadenitis in a case of right breast carcinoma--Diagnostic dilemma. AB - Coexistence of tuberculosis (TB) in the breast or axillary lymph nodes with breast carcinoma though rare is not unknown. A 55-year-old woman presented with right axillary and left supraclavicular lymphadenopathies with no detectable lesion in either breasts or left axilla. Right axillary lymph node excision biopsy revealed metastatic adenocarcinoma. Diagnostic workup showed intense fluorodeoxyglucose (FDG)-avid lymph nodes on the left side neck at level V, supraclavicular, axillary, subpectoral and para-aortic regions, and low FDG activity in the right breast. Core biopsy of right breast lesion was reported as invasive ductal carcinoma and cytology of multiple left axillary lymphadenopathies as reactive hyperplasia. Excision biopsy of the supraclavicular lymph nodes unveiled the diagnosis of TB. She underwent right-modified radical mastectomy followed by external beam radiotherapy, has completed antituberculous treatment and is on follow-up. Extrapulmonary TB though uncommon; may be found in certain cases. Clinicians must be aware of its existence. PMID- 26881598 TI - Atypical fibroxanthoma in a young female misdiagnosed clinically as a malignant melanoma--An unusual presentation. AB - Atypical fibroxanthoma (AFX) is an uncommon spindle cell tumor with intermediate or borderline malignant potential. Clinically, it may be misdiagnosed as a squamous cell carcinoma (SCC) or malignant melanoma. Solar irradiation has been implicated in its pathogenesis. The diagnosis of AFX rests on a combination of histopathological features and a negative immunohistochemical profile. AFX is a rare tumor usually found in sun exposed skin of head and neck region in elderly Caucasian men. Rarely, it has a second peak in young adults, where it is found in trunk and extremities. The present case is reported as AFX is quite unusual in a young female with a nodule in the leg which was clinically diagnosed as a malignant melanoma. Only a few cases of AFX have been reported in young women. This case highlights the fact that accurate diagnosis of atypical fibroxanthoma is very crucial so as to avoid overenthusiastic and overzealous treatment as required for a malignant tumor. PMID- 26881599 TI - Primary spinal melanoma treated with adjuvant radiotherapy and concurrent temozolomide: A case report and review of literature. AB - Primary intradural extramedullary melanoma of spinal cord is an extremely rare tumor.It accounts for approximately 1% of the total melanoma cases.We report a case of primary intradural extramedullary spinal melanoma in a 28-year-old gentleman who was managed with surgery followed by postoperative radiation with concurrent temozolomide followed by adjuvant temozolomide. The patient had a disease-free survival of 24 months, after which he developed marginal recurrence. To the best of our knowledge, this is the first case of a primary spinal cord melanoma. (PSCM) treated with postoperative radiotherapy with concurrent temozolomide followed by adjuvant Temozolomide. PMID- 26881600 TI - Renal cell carcinoma, unclassified with unique features. AB - Renal cell carcinoma, unclassified constitute about 3-4% of all renal carcinomas. It essentially is a tumor where more than morphological variants or subtypes are seen in a single tumor. Usually there is a mixture of 2-3 different types. However, in this particular case there were at least 5 different types of morphological patterns in a single tumor including areas of so-called rhabdoid differentiation. The patient underwent nephrectomy and has been asymptomatic for the last 3.5. years. To the best of our knowledge, this is the first case of its own kind in the published literature. PMID- 26881601 TI - Mucoepidermoid carcinoma of eyelid: A usual tumor at an unusual site. AB - Mucoepidermoid carcinoma is a malignant epithelial neoplasm comprising mucous, intermediate and epidermoid cells, arising mainly in salivary gland. It is extremely uncommon in ocular region, where it can arise in conjunctiva, lacrimal gland or lacrimal sac. The index case is being presented for its rarity and for highlighting the importance of meticulous sampling for correct diagnosis. A 68 year-old female presented with complaints of ulceration over right lower eyelid for 3 years. She underwent a local surgical excision 2 years ago after which she was asymptomatic for the following 1 year. Histopathological examination of excised specimen showed features of mucoepidermoid carcinoma. Mucoepidermoid carcinoma in ocular adnexa may be difficult to differentiate from its close mimickers like basal, squamous, sebaceous cell carcinoma and apocrine carcinoma. Meticulous sampling, judicious use of special stains and immunohistochemistry are pivotal in establishing the diagnosis. PMID- 26881602 TI - Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt. AB - Although rare, pancreatoblastoma is the most common pancreatic tumor in children. Cushing syndrome secondary to ectopic secretion of adrenocorticotropic hormone (ACTH) from a pancreatoblastoma is very rare with only two previously reported cases. We present the management and the lesson learnt in a 3-year-old child with recurrent pancreatoblastoma with Cushing syndrome. PMID- 26881603 TI - Langerhans cell histiocytosis diagnosed by FNAC of lymph nodes. AB - Langerhans cell histiocytosis (LCH) is a rare clonal disorder of unknown etiology and characterized by the proliferation of dendritic cells. LCH most commonly involves the bone followed by the skin and the lymph nodes. Recently, only a few cases of LCH with predominant lymph node involvement have been diagnosed by fine needle aspiration cytology (FNAC). A 2-year-old boy presented with generalized lymphadenopathy, fever, and cough. The patient had hepatosplenomegaly, anemia, and lytic lesions in the skull. FNAC from the largest submandibular lymph node showed features of LCH. The large cells of LCH showed positive immunostaining for S-100 protein on FNAC smears. Later, lymph node biopsy and immunohistochemistry against S-100 protein and CD1a confirmed the diagnosis of LCH. The patient was treated with chemotherapy and he is under regular follow-up. This case report highlights the importance of FNAC as a rapid and accurate investigation in the diagnosis of lymph node predominant LCH. PMID- 26881604 TI - Disseminated tuberculosis in a patient with recurrent transitional cell carcinoma of renal pelvis and bladder following intravesical BCG therapy: A report of a rare case. AB - Bacillus Calmette-Guerin (BCG) has been used as an intravesical instillation for nonmuscle invasive (superficial) bladder cancer for the last 3 decades. Although intravesical BCG therapy is well-tolerated by most of the patients, adverse reactions have also been reported which are usually local, benign, and self limited. Systemic complications such as miliary tuberculosis (TB) are very rare with few documented reports in literature. We hereby report a rare case of disseminated TB in bilateral lungs, adrenal, cervical, mediastinal, and para aortic lymph nodes in a patient with recurrent transitional cell carcinoma (TCC) of renal pelvis and urinary bladder. Peculiar feature of this case was the development of TB 2 years following last BCG instillation, which is unlike most of the cases in the literature where TB developed within few weeks of last dose of BCG. PMID- 26881605 TI - Calcification in transitional cell carcinoma of urinary bladder: Does it have any implication on calcium metabolism and its management? AB - Although transitional cell carcinoma (TCC) is most common histological subtype, calcification in TCC is rarely seen. We report a 64-year-old gentleman who on evaluation found to have calcification in TCC of urinary bladder and its implication on calcium metabolism and management. PMID- 26881606 TI - Desmoplastic small round cell tumor: Diagnostic dilemma and uncertain prognosis: Report of few cases. AB - Desmoplastic small round cell tumor (DSRCT) is rare and highly malignant neoplasm. DSRCT affects usually young males but can occur in adults also. Intra abdominal pelvic region is the preferred site. Though confirmed by histology, immunohistochemistry (IHC) plays a key role in diagnosis. IHC profile is characteristic, it shows simultaneous expression of epithelial (epithelial membrane antigen (EMA) and cytokeratin (CK)), muscular (desmin), and neural (neuron-specific enolase) markers. Many cases of DSRCT are diagnosed as poorly differentiated carcinoma due to lack of proper panel of IHC. It is difficult to predict if there has been a true increase in incidence. Prognosis is uncertain in such an aggressive neoplasm as chemotherapy (CT) or radiotherapy (RT) shows various outcomes. Here in; we report four cases, all of which showed diagnostic dilemma and uncertain prognosis. PMID- 26881607 TI - Spontaneous deep venous thrombosis: An unrecognized entity with sorafenib. AB - Hepatocellular carcinoma is the most common, malignant tumor of liver. Most cases of hepatocellular carcinoma are associated with either viral hepatitis or cirrhosis. But major risk factor for hepatocellular carcinoma in developing countries is mainly chronic hepatitis B. Sorafenib is one of the first-line drug which has been extensively used in metastatic and inoperable hepatocellular carcinoma. We report a rare case of spontaneous deep venous thrombosis of bilateral lower limbs as an important unrecognized side effect of sorafenib. PMID- 26881608 TI - Rare case of radiologically distinct but pathologically admixed vestibular schwannoma and meningioma in the cerebellopontine angle: A case report. AB - Primary intracranial tumors generally occur as solitary tumors. The association of two primary intracranial tumors of different histogenesis in the same individual is rare, except in cases of phakomatoses or radiation-induced tumors. Meningiomas and vestibular schwannomas (VSs) are one of the commonest tumors occurring intracranially. VS account for 80% of cerebellopontine angle (CPA) tumors, with meningiomas being the second most common tumor of the CPA. The occurrence of both a schwannoma and a meningioma in the CPA is rare. We report a case with coexistent CPA meningioma and VS, which were distinct radiologically on preoperative imaging, however had admixed areas of VS and meningioma on histopathological evaluation. PMID- 26881609 TI - Focal thyroid incidentaloma on whole body fluorodeoxyglucose positron emission tomography/computed tomography in known cancer patients: A case-based discussion with a series of three examples. AB - The importance, imaging characteristics and outcome of focal thyroid incidentaloma on fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) have been illustrated in this report. This is drawn from a series of three case examples of proven malignancy at different locations, with three different thyroid cytopathological diagnoses. Subsequently, a case-based discussion on present consensus of the management of this entity has been undertaken including certain specific aspects of PET-CT interpretation and its role in this setting. PMID- 26881610 TI - A case of invasive papillary breast carcinoma: Fierce facade with favorable prognosis. AB - Invasive papillary carcinoma of the breast is a rare, distinct variant comprising approximately less than 1-2% of all newly diagnosed cases of breast carcinoma and is usually found in postmenopausal women with a more favorable prognosis. We report an unusual case in a 45-year-old perimenopausal female who came with a complaint of lump in right breast for duration of 1 year. A simple mastectomy was undertaken for histopathological study and immunohistochemistry (IHC) which showed characteristic features of an invasive papillary breast carcinoma. We present this case in view of its rarity and to highlight this clinicopathological subtype for its good prognosis and to avoid overtreatment. PMID- 26881611 TI - Serous adenofibroma of ovary: An eccentric presentation. AB - Surface epithelial tumors of the ovary comprise over fourth of the ovarian neoplasms. Serous adenofibromas are lesser known variants of serous surface epithelial tumors. Though these tumors have a benign fate, yet they can be misinterpreted clinically and radiologically due to their borderline or malignant gross morphological as well as clinical presentation. The cell of origin of surface epithelial tumors of the ovary is histological debated; however, it is now ascertained to have origins from the ovarian cortical and surface lining. Adenofibromas are known to progress in an indolent manner with metachronous behavior for years. The present case is of an ovarian serous adenofibroma in a young female masquerading as peritoneal carcinomatosis. PMID- 26881612 TI - Brenner's tumor associated with ovarian mucinous cystadenoma reaching a huge size in postmenopausal woman. AB - A case of a 70-year-old Egyptian postmenopausal woman presenting a Brenner's tumor associated with mucinous cystadenoma weighing 20.7 kg is reported here. Patient was admitted in our hospital with abdominal pain of one-month duration. On abdominal ultrasound, a huge heterogeneous mass was found to encompass the whole abdomen. At laparotomy, a giant, right heterogeneous mass was encountered and removed intact by right salpingo-oophorectomy. On the seventh postoperative day, she was discharged without any problem. Her pathology report disclosed a 52 x 41 x 36 cm, partially solid, partially cystic mass diagnosed as benign Brenner's tumor with mucinous cystadenoma weighing 20.7 kg. This is the largest ovarian mass that is ever reported in our hospital and one of the largest among the reported cases in the literature. PMID- 26881613 TI - Satisfactory therapy results of combining nimustine with nicardipine against glioma at advanced stage. AB - Glioblastoma multiforme (GBM) is one of the most frequent brain cancers with a very poor prognosis. According to cancer stem cell (CSC) theory, therapies that are more specifically directed against CSCs might result in much more durable responses. Recently, we treated a case of GBM basing on the conception of CSC and gained a better clinic outcome. A 37-year-old male patient complained weakness of left limbs for 1 month. Magnetic resonance imaging (MRI) showed extensive lesions in the right hemisphere. We performed an intracranial tumor partial resection and the postoperative pathological diagnose was GBM. 1 month later, he received monthly chemotherapies with the combination of nimustine and nicardipine for totally 4 times. At the last chemotherapy, MRI scan showed the cancer almost completely disappeared with significantly improved clinic condition. The combination therapy of chemotherapeutics and nicardipine may be a promising treatment for patients of GBM at advanced stage. PMID- 26881614 TI - Sarcomatoid chromophobe renal cell carcinoma: A rare entity with prognostic significance. AB - Renal cell carcinoma (RCC) is the most common malignancy of the kidney and has multiple subtypes. The sarcomatoid variety is considered a form of dedifferentiated carcinoma. It is more commonly associated with clear cell variant but very few are associated with chromophobe RCC. When present, it is associated with a significant decrease in patient survival due to its rapid growth and intrusive behavior. Here, we report a unique case of sarcomatoid chromophobe RCC in a 35-year- old woman. PMID- 26881615 TI - Myxoid degeneration of appendix wall: An entity in search of identity: Report of two cases. AB - Myxoid degeneration of the appendix wall without accompanying acute appendicitis (AA) is rare. We report two cases of myxoid degeneration of appendix associated with appendiceal adhesions. Both the cases showed marked splitting and disruption of smooth muscle fibers of muscularis propria by abundant myxoid ground substance and dispersed degenerated hypereosinophilic myofibers with pyknotic nuclei. Scattered degenerated myocytes with vacuolated cytoplasm were also identified. Focal serosal fibrosis was observed in both cases. We reviewed other pathologic processes that involve the appendix such as fibrous obliteration, AA, and appendiceal mucinous neoplasm (AMN) and conclude that the constellations of pathologic findings described herein are unique. Nonneoplastic dissecting myxoid degeneration of the appendix muscularis propria has not been reported in the pathology literature to date. The pathologic nature of appendiceal mucinous stromal change remains unclear; however, we hypothesize that the lesion occurs as a consequence of traction related injury to the appendix. PMID- 26881616 TI - Tumor of the maxilla-odontogenic or glandular? A diagnostic challenge and the role of immunohistochemical markers. AB - Today's practice in medicine has reached remarkable change mainly due to the advances in the field. Odontogenic tumors represent a spectrum of lesions ranging from hamartomas to benign and malignant neoplasms. Rarely, odontogenic tumors pose a challenge due to varied histological features. But appropriate and accurate diagnosis is crucial for further treatment and follow-up as these have an influence on the prognosis. In such situations, immunohistochemical. (IHC) markers play a significant role in the differentiating various lesions. Within its palette of histology, there are multiple histopathological presentations, many a times these features come in an intermixed pattern simulating different origin. We here, report such a case presented in a 70-year-old female came with a complaint of swelling in the posterior maxilla. The microscopic findings were indicative of a benign neoplasm. To know the nature of the lesion and arrive at a diagnosis, many IHC markers were used. Based on all these findings, a final diagnosis of unicystic ameloblastoma was arrived. PMID- 26881617 TI - Primary choriocarcinoma of appendix mimicking acute appendicitis. AB - Choriocarcinoma is a malignant trophoblastic cancer, the incidence of primary choriocarcinoma (PCC) of the gastrointestinal tract (GIT) being extremely rare, with only 14 cases being reported in worldwide literature. Here we present an extremely rare case of PCCof the appendix in a 32-year-old male who presented with acute pain abdomen. Histopathological examination revealed PCC of the appendix. Examination of the testis was unremarkable. Further investigations revealed a very high serum beta-human chorionic gonadotropin (b-HCG) titer with a normal carcinoembryonic antigen (CEA). Radiological imaging showed multiple areas of liver metastasis. Chemotherapy-based treatment with bleomycin, etoposide, and cisplatin (BEP) regime was advised, however the patient failed to follow-up for further management. PMID- 26881618 TI - Kimura's disease embedding radial artery: A very rare presentation. AB - Kimura's disease (KD) was first described in 1937 by Kimm and Szetoas a reactive, self-limiting, painless, persistent lesion mimicking neoplasm and described it as eosinophilic hyperplastic lymphogranuloma. The present nomenclature was given by Kimura et al., in 1948. It occurs most often in young and middle-aged Asian males. It is most common in head and neck region, involvement of peripheral vasculature although very rare has been documented. PMID- 26881619 TI - Duodenoduodenal intussusception: Report of three challenging cases with literature review. AB - Small bowel intussusception is an uncommon condition with cases of duodenoduodenal intussusception (DDI) being exceptionally rare. Adult intussusception occurs infrequently and differs from childhood intussusception in its presentation, etiology, and treatment. DDI is very unusual due to the fixed position of the duodenum within the retroperitoneum. The lead point usually is hamartomatous polyp, adenoma, or adenocarcinoma. Only few cases of DDI in adults have been reported in the literature. We herein report a series of three cases of DDI encountered in a tertiary level research institute. All cases had underlying abnormality acting as lead point with different etiologies. DDI is a challenging condition due to its rarity and nonspecific presentation and should be considered in the differential diagnosis of gastric outlet obstruction, pancreatitis, and obstructive jaundice. We elaborate this condition with a detailed review of the literature to gain a better understanding of its clinical features and enable early diagnosis. PMID- 26881620 TI - Large pedunculated lipoma of the esophagus: Report of a case and review of literature. AB - Large pedunculated esophageal lipoma is uncommon. The presenting symptoms of esophageal lipoma are dysphagia, regurgitated mass, and persistent sensation of a lump in the throat. The most frequent location of the tumor pedicle is the upper esophageal sphincter. Here, we present the case of a 52-year-old man who had the symptoms of pharyngeal unwell and dysphagia. Panendoscopy showed a pedunculated tumor mass within the esophageal lumen with its peduncle arising from the cervical esophagus. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed that he might have anesophageal submucosal or intraluminal and pedunculated tumor mass. The tumor mass measured 25 * 16 * 45 mm in size. Cervical approachvia the right neck was performed for confirmation. After removal of the intraluminal mass, the patient became symptom free. Pathology showed a lipoma arising from the submucosa of the esophagus. PMID- 26881621 TI - Inappropriate antidiuretic syndrome hypersecretion after a single dose of cisplatin. AB - Severe hyponatremia with seizure owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral/renal salt wasting syndrome related with high mortality. The correct diagnosis of the hyponatremia for each case is important because of the alteration of the treatment approach. SIADH is an important clinical manifestation that does not occur after all chemotherapy courses. We cannot estimate whether the disease will occur on, which course of the chemotherapy in this case. PMID- 26881622 TI - An unusual case of eyelid metastasis from a rectal primary. AB - A 26-year-old, human immunodeficiency virus. (HIV).negative male, a diagnosed case of locally advanced adenocarcinoma rectum underwent diversion colostomy and received preoperative radiotherapy with three-dimensional conformal radiotherapy. (3DCRT) to a dose of 25 Gy/5 Fx/8. days to 95% planning target volume. (PTV) with 3-field technique. (right and left lateral and posterior) by 6 and 15 MV photons. Postradiotherapy contrast-enhanced computed tomography. (CECT) chest and abdomen showed progressive disease. He was reviewed by oncosurgeon and considered inoperable. He presented with a swelling over upper eyelid, which on biopsy was proven as metastatic adenocarcinoma. He received three cycles of weekly chemotherapy and was planned for excision and reconstruction of eyelid. He finally succumbed due to small bowel obstruction, acute renal failure, and septicemia after an overall duration of survival of seven months. Eyelid metastases occur in less than one percent of malignant eye lesions in adults. To the best of our knowledge, this is the first case reported with a primary in rectum. PMID- 26881623 TI - Pleomorphic liposarcoma arising in a malignant phyllodes tumor of breast: A rare occurrence. AB - Primary malignant phyllodes tumor of the breast accounts for 0.3-1% of all the tumors of breast and only a couple of cases of pleomorphic liposarcoma (PL) arising in a malignant phyllodes (MP) tumor have been reported. A thorough sampling is most essential in phyllodes tumor, not only to detect high grade component of the neoplasm but also to diagnose heterologous elements in the same lesion elsewhere, as it may affect the prognosis adversely and may have a greater metastatic potential. PMID- 26881624 TI - Pseudoangio-matous stromal hyperplasia: A rare tumor of the breast. AB - Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast entity described first by Vuitch et al., in 1986. PASH is a benign stromal lesion containing complex anastomosing channels lined by slender spindle cells. It can be mistaken with fibroadenoma on ultrasound examination and histologically with low-grade angiosarcoma and phyllodes tumor. Here, presented is a case report of a 30-year old female who presented with huge palpable lump in left breast. Ultrasonography revealed the lesion as giant fibroadenoma and fine needle aspiration cytology report was suggestive of cystosarcoma phyllodes. Excision and reduction mammoplasty was done and histopathology report was suggestive of PASH. PMID- 26881625 TI - Initial presentation of hepatocellular carcinoma as soft tissue swelling of the forearm: A rare cytomorphological diagnosis. AB - Bone is quite an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC). We report a rare case of HCC presenting as a rapidly progressive painful soft tissue swelling with isolated metastasis to the radius bone of right forearm. The present article emphasizes the point that HCC should be considered in the differential diagnosis of patients presenting with palpable soft tissue swelling with destruction of the underlying bone. Fine-needle aspiration cytology (FNAC) of the soft tissue mass revealed cytomorphological features of HCC. The primary tumor of the liver was diagnosed retrospectively, following FNAC of the osteolytic lesion in the right radius bone, which revealed HCC. PMID- 26881626 TI - Ectopic thymoma presenting as a large intrathoracic mass. AB - Thymoma is an epithelial neoplasm of the thymus, which commonly lies in the anterior mediastinum. Unusually it can be found in other locations as well. Ectopic thymoma rarely presents as an intrathoracic tumor. We report a case of an ectopic thymoma presenting as a giant right intrathoracic tumor that was treated with resection. The patient was a 49-year-old postmenopausal lady who presented with heaviness in chest and breathlessness. Detailed investigation including chest computed tomography scan and magnetic resonance imaging revealed a well defined large solid tumor in the right thoracic cavity. Surgery was performed based on the radiological findings. A large solid tumor measuring 12 cm x 10 cm x 8 cm was found in the thoracic cavity, adherent to the pericardium, diaphragm and the right mediastinal pleura without apparent invasion. The tumor was completely resected. The diagnosis given as World Health Organization classification-Type B1 Muller-Hermelink classification-predominantly cortical thymoma. PMID- 26881627 TI - Adenocarcinoma of urinary bladder: A report of two patients. AB - Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2. PMID- 26881628 TI - Spontaneous ante-grade enteral migration of jejunostomy tube: A rare complication. AB - Ante-grade migration of a feeding jejunostomy tube is a rare occurrence. A 47 year-old lady with hypopharyngeal malignancy underwent surgical placement of jejunostomy tube. Eight months later, she came with disappearance of the tube from skin surface. Clinical examination revealed skin erosion and disappearance of previously placed tube. Abdominal radiograph showed radio.opaque tube in the abdomen in its entirety. The patient underwent reoperation to establish enteral feeding route and at the same time retrograde extraction of the tube (from proposed site for placement of jejunostomy tube). Use of proper fixation, placement of tube with dilated distal ends can potentially prevent these complications. PMID- 26881629 TI - A rare association of sarcoid-like granuloma with renal cell carcinoma. AB - Non-necrotizing epithelioid granuloma has been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma, and Hodgkin's lymphoma. They are designated as sarcoid-like reaction, in absence of any evidence of systemic sarcoidosis. But granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. This reaction may have some prognostic importance also. We describe a rare case of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma, in a 42-year-old lady without any evidence of systemic sarcoidosis. PMID- 26881630 TI - Ameloblastic fibroma with ghost cell differentiation and calcification: A unique case report. AB - The ameloblastic fibroma (AF) is an uncommon odontogenic tumor that may present an aggressive behavior and may have potential for malignant transformation. Ghost cell differentiation within AF is extremely rare. There are only seven cases in English literature in which ghost cells are found in AF but all these previously reported cases were associated with typical calcifying odontogenic cyst. Here, we present a unique case in 3(1/2)-year-old child with solid lesion which comprised odontogenic epithelium strands, islands, and myxoid ectomesenchyme with focal areas of ghost cell differentiation and calcification associated with neoplastic epithelium. PMID- 26881631 TI - Extramedullary hematopoiesis on 18F-FDG PET/CT in a patient with thalassemia and nasopharyngeal carcinoma: A case report and literature review. AB - Extramedullary hematopoiesis (EMH) occurs in various bone marrow disorders and is most commonly seen in thalassemia and myelofibrosis. Here, we report a patient with beta-thalassemia and nasopharyngeal carcinoma having intrathoracic EMH. Our patient is a 42-year-old man who complained of chest discomfort for a month. He was confirmed nasopharyngeal carcinoma (T3N2M0) by histopathology and received chemoradiotherapy 4 months ago. The patient had a long history of beta thalassemia and a splenectomy due to splenomegaly at 12 years of age. Computed tomography (CT) scan of the chest showed multiple soft tissue masses in bilateral thoracic cavities. 18F-FDG-PET showed no obvious increase of fluorodeoxyglucose (18F-FDG) uptake by the lesions, with an SUVmax value of approximately 2.19. These lesions were considered EMH. The patient had been followed up for more than 1 year, and there were no changes of the lesions in the thoracic cavities. PMID- 26881632 TI - Mediastinal mixed germ cell tumor in an infertile male with Klinefelter syndrome:A case report and literature review. AB - Klinefelter syndrome (KS) is a well-documented abnormality of the sex chromosome, with an incidence of 1 in 600 newborn males. It is characterized by a 47, XXY or a mosaic karyotype, hypergonadotrophic hypogonadism, infertility, reduced body hair, gynecomastia, and tall stature. Different neoplasms such as breast, testicular, and lymphoreticular malignancies may occur in 1% to 2% of the cases with KS. Herein we describe a case of mediastinal mixed germ cell tumor (GCT) in a 40-year-old male with KS. Interestingly, this case also had mitral valve prolapse, and an incidental papillary microcarcinoma of the thyroid gland. In view of the presence of pulmonary nodules, antemortem differential diagnoses considered were mycobacterial infection, lymphoma, thymic carcinoma, and a primary/metastatic neoplasm of the lung. As GCT was not considered, the serum markers of a GCT were not performed. The diagnosis of this rare mediastinal mixed GCT with KS was made at autopsy. PMID- 26881633 TI - Adenosquamous carcinoma of oral cavity. AB - Adenosquamous carcinoma is a rare malignant epithelial neoplasm characterized by the presence of both areas of squamous cell carcinoma and adenocarcinoma. Only few cases of oral adenosquamous carcinoma have been previously reported in the literature. It has been described as a squamous cell carcinoma subtype with a high infiltrative capacity. This paper reports a rare case of adenosquamous carcinoma that involved the upper left buccal mucosa in a 55-year-old man. PMID- 26881634 TI - Primary cardiac lymphoblastic B-cell lymphoma: Should we treat more intensively? AB - Primary cardiac lymphoma (PCL) is a rare neoplasm, the majority of cases of which are non-Hodgkin's, diffuse large B-cell (DLBCL). We report the first case of an adult with PCL B-cell lymphoblastic lymphoma whose disease evolution was grim. A 52-year-old male reported dyspnea and facial swelling lasting for 4 months and upon a physical examination he presented bradycardia, jugular venous engorgement, and hypophonesis of cardiac sounds. An electrocardiography (Echo) revealed a right atrial mass and nodules at the pericardium. The patient was treated with R Hyper-CVAD (rituximab plus cyclophosphamide, vincristine, doxorubicin, and dexamethasone) and presented very short remission. At this time, we used R-ICE (rituximab plus ifosfamide, carboplatin, and etoposide) chemotherapy and the patient underwent complete remission after two courses and received autologous bone marrow transplantation (auto-BMT). After 75 days of follow-up, the patient reported dyspnea and a new Echo showed a recurrence of the disease. The patient died due to cardiac failure. PCL is a rare disease with an unfavorable prognosis and a prompt diagnosis and treatment are fundamental to survival. We believe that more intensive therapies, such as auto-BMT, should be considered as a first treatment option. PMID- 26881635 TI - Cytomorphology of lung metastasis of pure choriocarcinoma of testis in a 58-year old male. AB - Choriocarcinoma is malignancy arising from the trophoblastic tissue. Pure choriocarcinoma is rare in testis. Choriocarcinoma of testis is more commonly associated with other germ cell tumors. The usual age of presentation is 2nd-3rd decade. Distant metastasis is known to occur in choriocarcinoma. We present a rare case of testicular pure choriocarcinoma in a male patient. The patient was treated with orchidectomy, lymphadenectomy, and chemotherapy. Three months later the patient presented with hemoptysis and a lung mass. The aspiration cytology of the lung mass revealed metastatic deposits of syncytiotrophoblastic and cytiotrophoblastic cells. We are reporting this case due to its rarity, rare age of presentation, and characteristic cytology at metastatic focus. PMID- 26881636 TI - Diagnosis of leiomyosarcoma of colon. AB - Leiomyosarcomas of colon are rare tumors accounting for less than 1% of cases which are often misdiagnosed and confused with gastrointestinal stromal tumor (GIST). We report a case of 54-year-old male presenting with abdominal pain with computer tomography (CT) showing a retroperitoneal mass. He underwent laparotomy and surgical excision of mass was done. On pathological examination, microscopy was suggestive of GIST, but immunohistochemistry was positive for desmin and ultimately this case was diagnosed as leiomyosarcoma. PMID- 26881637 TI - Cerebellar metastases of recurrent phyllodes tumor breast; a rare phenomenon reflecting the unpredictable outcome. AB - Carcinomas of lung, breast, colon, kidney, and malignant melanomas are the most common malignancies that metastasize to the central nervous system (CNS). Phyllodes tumor is a rare fibroepithelial tumor of the breast, often having unpredictable recurrences, with increasing histological grade and distant metastasis. Malignant forms exist, which may develop distant metastases usually to the lung, pleura, bone, and liver. CNS metastasis of phyllodes tumor is rare and associated with a poor prognosis, with resistance to chemotherapy and radiation. We present a rare case of cerebellar metastasis in recurrent phyllodes tumor breast with subsequent rapid downhill course. PMID- 26881638 TI - Florid reactive lymphoid hyperplasia (lymphoma-like lesion) of cervix: A diagnostically challenging case and a brief review of literature. AB - Large lymphoid proliferations are usually regarded as synonymous with lymphomas. However, lymphoma-like lesions. (LLLs) of the cervix are amongst the exception. We report a 46-year-old woman who complained of irregular menses and was found to have superficial erosion in cervix, which on biopsy showed clusters of large atypical appearing lymphoid cells admixed with smaller reactive lymphoid cells. On immunohistochemistry, these large cells were strongly positive for CD20 and CD30 and the background cells were reactive to CD3. Based on the superficial nature of infiltrate and absence of a mass-forming lesion, a diagnosis of LLL of cervix was made. Despite a benign diagnosis, a hysterectomy was done on patient's insistence and only a focus of lymphoid cells similar to biopsy was seen on the operated specimen. Patient is free of disease on follow-up. PMID- 26881639 TI - Atypical clinical presentation of orbital adenoid cystic carcinoma. AB - Orbital adenoid cystic carcinoma (ACC) always originates from epithelia of lacrimal gland and typically presents as lacrimal fossa mass. We describe two cases of biopsy-proven orbital ACC without definite lacrimal gland mass. Orbital images showed that the lesions of the two patients were located mainly in retrobulbar space, extending posteriorly to the orbital apex. Both of them had relatively normal lacrimal gland images. Each patient underwent complete ophthalmologic examination and orbital surgery. Histopathological assessment proved to be ACC. Immunohistochemistry showed invasion of the nerve fibers. This report suggests the possibility of orbital ACC without obvious lacrimal gland mass. The two cases of atypical orbital ACC reinforced the differential diagnosis of the diseases. PMID- 26881640 TI - HMB-45 negative multifocal malignant perivascular epithelioid cell tumor of the soft tissue responding to sirolimus: First case report from India. AB - Perivascular epithelioid cell tumor (PEComa) is a group of sarcomas that exhibit a myomelanocytic phenotype and possess a unique cell type in the perivascular epithelioid cell. Traditionally HMB-45 immunoreactivity is the first criteria required to consider a tumor to be PEComa. We report a case of multifocal PEComa with negative HMB-45 marker. The patient presented with three big ulceroproliferative lesions; two over right thigh and one over the scalp in the right frontal region. The patient was prescribed with oral sirolimus to which good response was seen. To the best of our knowledge, this is the first case of HMB-45 negative multifocal malignant PEComa from India. PMID- 26881641 TI - Discoid lupus erythematosus-related squamous cell carcinoma of the lip in an HIV seropositive black male. AB - Discoid lupus erythematosus (DLE) is an autoimmune disease commonly affecting sun exposed areas of the skin. Subjects with DLE have high-levels of plasmacytoid dendritic cells -derived interferon-alpha, which mediates both loss of immune tolerance to self-antigens and exaggerated inflammatory state, and supports proliferation and differentiation of hyperactive B-cells. In a few cases, DLE of the lips, scalp, ears or nose may eventually progress to squamous cell carcinoma (SCC). Photosensitivity and the long-standing immune-mediated chronic inflammation and dysregulated healing characterized by atrophy, hypopigmentation or scarring inherent to DLE are risk factors for progression to SCC. We review some aspects of the pathogenesis of DLE and the possible roles of inflammation and photosensitivity in the carcinomatous transformation of DLE keratinocytes, and present an illustrative case of DLE of the lower lip in an HIV-tuberculosis co-infected black person, that progressed to SCC. PMID- 26881642 TI - Progressive paraplegia caused by recurrence of mantle-cell lymphoma with atypical spinal magnetic resonance imaging features. AB - We describe a case of paraplegia, which had progressed rapidly in a 60-year-old Japanese man with mantle-cell lymphoma. (MCL). He admitted to our hospital due to lumbago and progressive muscle weakness of bilateral lower thighs lasting for 1. month, while he had the history of the systemic chemotherapy for MCL since 10 months. Magnetic resonance imaging. (MRI) revealed a wide-spreading intradural tumor situated in the spinal canal from L1 to L5 with an intervertebral slipped disk as the only site of recurrence. Laminectomy followed by salvage chemotherapy led disappearance of lumbago and paraplegia of the bilateral lower extremities. Although wide-spreading tumor formation in spinal canal without other involvement sites is very rare in MCL, physicians should be aware of such patterns of central nervous system. (CNS) relapse for the early diagnosis and adequate selection of treatment modality. PMID- 26881643 TI - Very late recurrence of an apparently benign pheochromocytoma. AB - Pheochromocytoma is a tumor that has the probability to relapse in about 10% of surgically treated cases. Currently, the only recognized criteria of malignancy in these neoplasms are the evidence of metastasis at non-chromaffin sites. No reliable clinical or histopathological parameter has been, so far, identified to predict malignancy in patients with diagnosis of primary pheochromocytoma. Several authors has attempted to propose morphologic features to detect potentially malignant pheochromocytomas, but there are still too many reported cases of recurrence, also after decades, in tumors that, according to the current knowledge, are considered "benign". Here we report a case of recurrence, after 25 years, of a pheochromocytoma that had not enough criteria to be considered as malignant. PMID- 26881644 TI - Lung reexpansion of obstructive atelectasis caused by radiotherapy after continuous gefitinib treatment in nonsmall cell lung cancer. AB - A 75-year-old male was diagnosed with central squamous cell carcinoma of the left lung, who has been given 3-dimensional conformal radiotherapy of total dose with 60 Gy in 30 fractions. Three years later, the tumor relapsed in situ and he received another stereotactic radiotherapy with a total dose of 40 Gy at a margin of planning target volume (PTV) in 10 (5 fractions/week) at 4 Gy/fraction. Gefitinib (250 mg/day) was initiated immediately after radiotherapy. Obstructive atelectasis in the left lung and increased pleural effusion occurred at the fourth month after radiotherapy. As this patient has been detected with deletion in exon 19 of the EGFR gene, gefitinib was continuous administered without interruption. After another 4 months, the atelectasis in the left lung reexpanded significantly. To the best of our knowledge, this is the first report in the literature that EGFR tyrosine kinase inhibitors (EGFR-TKI) reversed the radiation atelectasis of pulmonary in the nonsmall cell lung cancer (NSCLC) patient. PMID- 26881645 TI - Papillary thyroid carcinoma and subclinical thyrotoxicosis: Brief insight into the thyroid regulators other than thyroid stimulating hormone. AB - Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. It usually develops in euthyroid patients with history of long standing Hashimoto's thyroiditis. Here, we describe the development of PTC in a seronegative patient with subclinical thyrotoxicosis. We suggest that any cold nodule having high-risk features on ultrasonography in hyperthyroid patients should be thoroughly evaluated for the possibility of a thyroid malignancy and the possible role of nonthyroid stimulating hormone regulatory molecules, in thyroid carcinogenesis needs to be further explored. PMID- 26881646 TI - A complex three-way translocation with deletion of the TP53 gene in a blast crisis chronic myeloid leukemia patient. AB - Chronic myeloid leukemia (CML) is characterized by the Philadelphia (Ph) chromosome created by the reciprocal translocation t(9;22) (q34;q11), resulting in the chimeric BCR-ABL oncogene. Variant Ph' chromosome translocations involving additional chromosomes are seen in 5-10% of CML cases. In the present study, a novel case of Ph' chromosome-positive CML is reported, with a three-way translocation involving chromosomal regions, 9q34, 22q11.2 and 17p11.2, with additional secondary changes. The three-way translocation has resulted in a deletion of the TP53 gene located on the chromosome 17p13.1 locus. Deletion of the TP53 gene may be a major contributing factor in the development of resistance to imatinib and blast crisis. PMID- 26881647 TI - Gastrointestinal stromal tumor and isolated anterior tibial muscle metastasis as first recurrence. AB - In the presented case, we report gastrointestinal stromal tumor (GIST) in a patient using adjuvant imatinib in whom isolated metastasis to anterior tibial muscle as first recurrence was diagnosed. A 66-year-old woman was diagnosed with GIST on October 2012 and was followed up with adjuvant imatinib until June 2014. In this time, there was a nodular and fixed lesion with 1.5-2 cm of diameter in right lateral pre-tibial area. The lesion was resected, and it was reported as GIST metastasis by pathologist. GIST metastasis to muscle under knee is a generally unexpected area for any tumor metastasis. In modern treatment era, due to the increasing survival of the patients with GIST using targeted therapy, the metastatic pattern and behavior of GIST may be changing. PMID- 26881648 TI - Osteosarcoma of larynx: A rare case report with review of literature. AB - Laryngeal osteosarcoma is an extremely rare and aggressive malignancy. Only very few cases of primary laryngeal osteosarcomas are reported in literature, and all have a dismal prognosis. A 50-year-old male presented with recurrent hoarseness of voice and was evaluated and diagnosed as sarcoma larynx. Detailed histopathology report of laryngectomy specimen revealed presence of osteoid, which confirmed the diagnosis of osteosarcoma larynx. He was further treated with adjuvant chemotherapy and radiation and is disease free after 9 months. Surgery remains the mainstay of treatment in this disease and role of adjuvant chemotherapy and radiotherapy is still evolving. PMID- 26881649 TI - Enigma of myoepithelioma at the base of tongue: A rare case report and review of literature. AB - Myoepithelioma, once considered to be a type of pleomorphic adenoma, is a rare benign tumor of the salivary glands. This uncommon tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the palate. We report a case of myoepithelioma located at the base of tongue, a rare site, in a 48-year-old male, composed of spindle shaped myoepithelial cells. PMID- 26881650 TI - Giant dermatofibrosarcoma protuberans: A rare presentation over face. AB - Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive, soft tissue tumor. Its occurrence over face is very rare. We are presenting a case of giant DFSP over left cheek, which produces oncological, functional and esthetic challenges and deals by multidisciplinary team. We also reviewed the relevant literature in short. PMID- 26881651 TI - Fulminant Buddchiari syndrome caused by renal primitive neuroectodermal tumor with inferior vena cava thrombus extending to atrium. AB - Primitive neuroectodermal tumors (PNET) of the kidney are rare, the diagnosis usually being made at histopathology. A young female presented with a massive right renal mass with features of hepatic dysfunction. Computed tomography scan of the abdomen revealed a large tumor of right kidney with tumor thrombus extending from inferior vena cava (IVC) to right atrium with features suggesting Buddchiari syndrome (BCS). Needle biopsy of mass showed a round cell neoplasm and positive staining for neuron specific enolase and minimum inhibitory concentration-2 on immunohistochemistry. She was managed with neo-adjuvant chemotherapy, surgery and adjuvant chemotherapy. To the best of our knowledge this is the first case of renal PNET with inferior IVC tumor thrombus extending to right atrium with BCS. We suggest that renal PNET should be kept in mind as a differential diagnosis in young adults presenting with a large kidney mass extending to IVC that shows evidence of necrosis on imaging, which may be associated with BCS as in index case. PMID- 26881652 TI - Unusual presentations of intracranial meningiomas: Report of two cases and review of the literature. AB - Meningiomas at extracranial sites are uncommon clinical presentations. They may present in the form of benign, slow.growing masses or may exhibit aggressive malignant behavior. We report two cases of intracranial meningiomas presenting at extracranial sites that are, at the sinonasal tract/external auditory canal and as a neck mass. The clinical presentations, histopathological features and appropriate management are discussed. PMID- 26881653 TI - Clear cell renal cell carcinoma with osseous metaplasia: Rare case report. AB - Osseous metaplasia with clear cell renal cell carcinoma (RCC) is exceedingly rare. There are less than 20 reported cases of osseous metaplasia in association with RCC. We present a case of 39-year-old male patient presented to outpatient department with complaints of pain in the left lumbar region since 4 years. Computed tomography scan revealed a heterogeneous enhanced mass lesion having areas of necrosis and specks of calcification involving the left kidney. Clinicoradiological diagnosis of RCC was made and left radical nephrectomy was performed. Histological sections from the growth revealed features of clear cell carcinoma Fuhrman grade-2 with a focal area of metaplastic bone formation. The prognostic implications of calcification per se are not very clearly mentioned in the literature. Patients with osseous metaplasia generally present with early stage disease and a favorable prognosis. However, few of them were of high grade and poorer prognosis. PMID- 26881654 TI - The utility of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography for detecting lung and esophagus multiple primary cancers involved in the larynx: Two case reports. AB - Multiple primary cancers involved in the larynx of differentiating synchronous multiple primary cancers from metastasis can often be very difficult, especially when they have the same histology. However, it is very important because the therapeutic approach is completely different. Clinical situations like this appear to be increasing as a result of the recent popular use of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography. Herein, we report two cases of multiple primary cancers involved in the larynx. PMID- 26881655 TI - Space occupying lesion (paraganglioma) of the urinary bladder in a young male: A case report and brief review of the literature. AB - Urinary bladder paragangliomas are rare with a reported incidence of <1% of bladder tumors. In the absence of typical clinical features, histopathology helps in rendering definitive diagnosis. We describe a case of nonfunctional urinary bladder paraganglioma in a 28-year-old male who presented with the chief complaint of abdominal pain. The final diagnosis was made by histopathological and immunohistochemical analysis. It is important to distinguish paraganglioma from urothelial carcinoma as the treatment differs. This is an additional case of nonfunctional urinary bladder paraganglioma in a male patient with a brief review of the literature. PMID- 26881656 TI - Drop metastases to the spinal cord from infratentorial glioblastoma multiforme in post-temozolomide era. AB - Drop metastases from glioblastoma multiforme (GBM) to the spinal cord are extremely rare in clinical practice. We report herewith multiple drop metastases to the cervical and thoracic spinal cord presenting as paraplegia in a patient treated initially with tumor resection followed by chemoradiation and later with temozolomide-.based adjuvant chemotherapy. PMID- 26881657 TI - Congenital nasopharyngeal teratoma causing airway obstruction in the newborn. AB - Teratomas are the most common congenital tumors, but teratomas of the nasopharynx are rare in neonates. The present report is about an 18-day-old girl child with a nasopharyngeal teratoma protruding from the oral cavity. The tumor almost completely obstructed the airways and necessitated immediate intervention. The tumor was successfully removed by the transpalatal route. Histological examination showed that it was a mature teratoma. The case with its related differential diagnosis is discussed here. PMID- 26881658 TI - Sacrococcygeal teratoma with complete adrenal gland. AB - Sacrococcygeal teratoma is the most common congenital neoplasm in neonates. We came across a post term (42 weeks) newborn baby girl delivered by normal vaginal route. The baby presented with a large soft, cystic mass over the sacrococcygeal region. Radiological examination showed a soft tissue mass with variegated appearance. Complete excision of the mass was done. Histopathological examination revealed the mass to be a mature sacrococcygeal teratoma with the extremely uncommon finding of a complete adrenal gland within the teratoma sac. Sacrococcygeal teratoma is a component of a continuum with other tumors including fetiform teratoma, fetus in fetu, parasitic and conjoint twins. PMID- 26881659 TI - Myxoid adrenal cortical adenoma in an infant: An unusual morphology. AB - Myxoid adrenal cortical neoplasms are rare. To the best of our knowledge, no such case has been reported in pediatric or infantile age group till now. Here we report a case of non-functional myxoid adrenocortical adenoma (ACA) in a 7-month old girl, who presented with a large mass in the abdomen. Microscopically, the tumor was composed of alveolar clusters of cells with focal pseudoglandular architecture in a background of abundant alcian blue positive myxoid matrix. Compressed rim of adrenal tissue was identified at periphery. The patient was put on a close follow-up in view of scarce literature on the subject. She has been doing fine without any recurrences. Myxoid adrenal cortical tumors expand the differential diagnoses of a myxoid neoplasm in retroperitoneum. PMID- 26881660 TI - Lipoblastoma and lipoblastomatosis: A clinicopathological study of six cases. AB - Lipoblastoma and lipoblastomatosis are benign adipocytic tumors seen in children less than 3 years of age. Awareness amongst surgeons of this fast growing lipomatous tumor in young children is important to avoid mutilating surgery and chemotherapy. Histological diagnosis of lipoblastoma is sometimes difficult because of close resemblance with myxoid, round cell, and well-differentiated liposarcoma. We came across a series of six cases of lipoblastoma/lipoblastomatosis, over the last 10 years (2002-2012). Of these, we had three cases of lipoblastomatosis, one of which recurred after 2 months. All others were resected completely and successfully. PMID- 26881662 TI - International twinning partnerships: Promoting cancer research and therapeutics in developing countries. PMID- 26881661 TI - The role of mast cell density in tumor-associated angiogenesis and survival of squamous cell carcinoma of the lung. PMID- 26881663 TI - The use of Gc protein-derived macrophage activating factor for management of thyroid cancer. PMID- 26881664 TI - Neoadjuvant chemotherapy with cetuximab for locally advanced penile cancer. PMID- 26881665 TI - Micronuclei in breast aspirates. PMID- 26881666 TI - Patient-specific imaging schedules. PMID- 26881667 TI - Pros and cons of using Facebook in pediatric oncology. PMID- 26881668 TI - Lasers in the management of chemoradiotherapy-induced oral mucositis. PMID- 26881669 TI - Second primary malignancies in chronic myeloid leukemia patients. PMID- 26881670 TI - Disseminated tuberculosis presenting as prolonged fever without source in a pediatric patient with acute lymphoblastic leukemia. PMID- 26881671 TI - Solitary metastatic tumor of breast presenting as large solitary expansile lesion of tibia mimicking aneurysmal bone cyst. PMID- 26881672 TI - The rapid resolution of pseudohyperphosphatemia in an IGAkappa multiple myeloma patient after therapy with a bortezomib-containing regimen: Report of the first case. PMID- 26881673 TI - Does a pathological fracture affect the prognosis in patients with osteosarcoma of the extremities? PMID- 26881674 TI - Bilateral axillary node metastases from anaplastic lymphoma kinase positive non small cell lung cancer. PMID- 26881675 TI - Mucoepidermoid carcinoma in the upper lip: An unusual occurrence. PMID- 26881676 TI - Contamination of arsenic species in rice and the calculation for risk of cancer. PMID- 26881677 TI - Population based cancer registry in the developing countries: A first step towards cancer control programs and research. PMID- 26881678 TI - Intracranial high grade glioma masquerading as a skull base lesion: Report of two unusual cases. PMID- 26881679 TI - Giant vulval neurofibroma: A rare entity with review of literature. PMID- 26881680 TI - MutY homolog Y165C and G382D mutations in cholangiocarinoma: No role. PMID- 26881681 TI - Mucinous carcinoma of the gall bladder--An incidental diagnosis of a rare variant. PMID- 26881682 TI - Re: Lambda light chain myeloma presenting as nodular hepatic lesion: A clinical rarity. PMID- 26881683 TI - Pruning inaccuracies in staging of inoperable carcinoma oesophagus. PMID- 26881684 TI - Solid pseudo-papillary tumor of pancreas: Indian perspective. PMID- 26881685 TI - Undifferentiated carcinoma of pancreas with osteoclast-like giant cells mimicking a pseudopancreatic cyst. PMID- 26881686 TI - Primary neuroendocrine mediastinal tumor presenting with carcinoid syndrome and left supraclavicular lymphadenopathy. Clinico-radiological and pathological features. PMID- 26881687 TI - Rare case of primary cutaneous diffuse large B-cell lymphoma-leg type with testicular infiltration. PMID- 26881688 TI - Pure epidermoid cyst of ovary. PMID- 26881689 TI - Orbital retinoblastoma: Prosthetic frontier. PMID- 26881690 TI - A case of heterotopic gastric patch of cervical esophagus: Cervical inlet patch. PMID- 26881691 TI - Erratum: Changes in lymphocytes' telomerase activity by 4-1BB costimulation. PMID- 26881692 TI - Retraction: Colposcopy in oral epithelial dysplasia: Seeing the unseen, a pilot study. PMID- 26881693 TI - The variance of the adjusted Rand index. AB - For 30 years, the adjusted Rand index has been the preferred method for comparing 2 partitions (e.g., clusterings) of a set of observations. Although the index is widely used, little is known about its variability. Herein, the variance of the adjusted Rand index (Hubert & Arabie, 1985) is provided and its properties are explored. It is shown that a normal approximation is appropriate across a wide range of sample sizes and varying numbers of clusters. Further, it is shown that confidence intervals based on the normal distribution have desirable levels of coverage and accuracy. Finally, the first power analysis evaluating the ability to detect differences between 2, different adjusted Rand indices is provided. (PsycINFO Database Record PMID- 26881694 TI - Affordance-based perception-action dynamics: A model of visually guided braking. AB - Behavioral dynamics is a framework for understanding adaptive behavior as arising from the self-organizing interaction between animal and environment. The methods of nonlinear dynamics provide a language for describing behavior that is both stable and flexible. Behavioral dynamics has been criticized for ignoring the animal's sensitivity to its own capabilities, leading to the development of an alternative framework: affordance-based control. Although it is theoretically sound and empirically motivated, affordance-based control has resisted characterization in terms of nonlinear dynamics. Here, we provide a dynamical description of affordance-based control, extending behavioral dynamics to meet its criticisms. We propose a general modeling strategy consistent with both theories. We use visually guided braking as a representative behavior and construct a novel dynamical model. This model demonstrates the possibility of understanding visually guided action as respecting the limits of the actor's capabilities, while still being guided by informational variables associated with desired states of affairs. In addition to such "hard" constraints on behavior, our framework allows for the influence of "soft" constraints such as preference and comfort, opening a new area of inquiry in perception-action dynamics. PMID- 26881695 TI - Tool use and affordance: Manipulation-based versus reasoning-based approaches. AB - Tool use is a defining feature of human species. Therefore, a fundamental issue is to understand the cognitive bases of human tool use. Given that people cannot use tools without manipulating them, proponents of the manipulation-based approach have argued that tool use might be supported by the simulation of past sensorimotor experiences, also sometimes called affordances. However, in the meanwhile, evidence has been accumulated demonstrating the critical role of mechanical knowledge in tool use (i.e., the reasoning-based approach). The major goal of the present article is to examine the validity of the assumptions derived from the manipulation-based versus the reasoning-based approach. To do so, we identified 3 key issues on which the 2 approaches differ, namely, (a) the reference frame issue, (b) the intention issue, and (c) the action domain issue. These different issues will be addressed in light of studies in experimental psychology and neuropsychology that have provided valuable contributions to the topic (i.e., tool-use interaction, orientation effect, object-size effect, utilization behavior and anarchic hand, tool use and perception, apraxia of tool use, transport vs. use actions). To anticipate our conclusions, the reasoning based approach seems to be promising for understanding the current literature, even if it is not fully satisfactory because of a certain number of findings easier to interpret with regard to the manipulation-based approach. A new avenue for future research might be to develop a framework accommodating both approaches, thereby shedding a new light on the cognitive bases of human tool use and affordances. (PsycINFO Database Record PMID- 26881697 TI - Dietary restrictions, bone density, and bone quality. AB - Caloric restriction (CR), protein restriction (PR), and specific amino acid restriction (e.g., methionine restriction (MR)) are different dietary interventions that have been confirmed with regard to their comprehensive benefits to metabolism and health. Based on bone densitometric measurements, weight loss induced by dietary restriction is known to be accompanied by reduced areal bone mineral density, bone mass, and/or bone size, and it is considered harmful to bone health. However, because of technological advancements in bone densitometric instruments (e.g., high-resolution X-ray tomography), dietary restrictions have been found to cause a reduction in bone mass/size rather than volumetric bone mineral density. Furthermore, when considering bone quality, bone health consists of diverse indices that cannot be fully represented by densitometric measurements alone. Indeed, there is evidence that moderate dietary restrictions do not impair intrinsic bone material properties, despite the reduction in whole-bone strength because of a smaller bone size. In the present review, we integrate research evidence from traditional densitometric measurements, metabolic status assays (e.g., energy metabolism, oxidative stresses, and inflammatory responses), and biomaterial analyses to provide revised conclusions regarding the effects of CR, PR, and MR on the skeleton. PMID- 26881696 TI - Comparison of the Utility and Validity of Three Scoring Tools to Measure Skin Involvement in Patients With Juvenile Dermatomyositis. AB - OBJECTIVE: To compare the abbreviated Cutaneous Assessment Tool (CAT), Disease Activity Score (DAS), and Myositis Intention to Treat Activity Index (MITAX) and correlate them with the physician's 10-cm skin visual analog scale (VAS) in order to define which tool best assesses skin disease in patients with juvenile dermatomyositis. METHODS: A total of 71 patients recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study were included and assessed for skin disease using the CAT, DAS, MITAX, and skin VAS. The Childhood Myositis Assessment Scale (CMAS), manual muscle testing of 8 groups (MMT8), muscle enzymes, inflammatory markers, and physician's global VAS were recorded. Relationships were evaluated using Spearman's correlations and predictors with linear regression. Interrater reliability was assessed using intraclass correlation coefficients. RESULTS: All 3 tools showed correlation with the physician's global VAS and skin VAS, with DAS skin showing the strongest correlation with skin VAS. DAS skin and CAT activity were inversely correlated with CMAS and MMT8, but these correlations were moderate. No correlations were found between the skin tools and inflammatory markers or muscle enzymes. DAS skin and CAT were the quickest to complete (mean +/- SD 0.68 +/- 0.1 minutes and 0.63 +/- 0.1 minutes, respectively). CONCLUSION: The 3 skin tools were quick and easy to use. The DAS skin correlated best with the skin VAS. The addition of CAT in a bivariate model containing the physician's global VAS was a statistically significant estimator of skin VAS score. We propose that there is scope for a new skin tool to be devised and tested, which takes into account the strengths of the 3 existing tools. PMID- 26881700 TI - Clinical research activity in periodontal medicine: a systematic mapping of trial registers. AB - AIM: The primary aim of the study was to systematically map registration records on periodontal medicine in clinical trial registers. The secondary aim was to assess the evolution of periodontal medicine in clinical periodontal research as a whole. MATERIAL AND METHODS: We searched all registration records related to periodontology in the World Health Organization International Clinical Trials Registry Platform. For registration records classified in the field of periodontal medicine, we assigned the 2015 MeSH((r)) term for the most precisely corresponding systemic condition. RESULTS: Fifty-seven systemic conditions have been hypothesized to be linked with periodontal diseases, covering nearly 2% of the diseases indexed in MeSH. In addition to diabetes, cardiovascular disease or preterm birth, other systemic conditions have been the subject of registration records, such as anaemia, liver diseases, dyspepsia or ankylosing spondylitis. A trend towards increasing diversification of systemic conditions has appeared over time. About a third of registration records in clinical periodontal research deals with periodontal medicine. CONCLUSIONS: Periodontal medicine now constitutes an important part of clinical periodontal research. Research activity in periodontal medicine has grown continuously since the early 2000s, and exploration of registers gives a useful up-to-date snapshot of this constantly evolving field of research. PMID- 26881698 TI - Increased DNA Methylation and Reduced Expression of Transcription Factors in Human Osteoarthritis Cartilage. AB - OBJECTIVE: To analyze the methylome of normal and osteoarthritic (OA) knee articular cartilage and to determine the role of DNA methylation in the regulation of gene expression in vitro. METHODS: DNA was isolated from human normal (n = 11) and OA (n = 12) knee articular cartilage and analyzed using the Infinium HumanMethylation450 BeadChip array. To integrate methylation and transcription, RNA sequencing was performed on normal and OA cartilage and validated by quantitative polymerase chain reaction. Functional validation was performed in the human TC28 cell line and primary chondrocytes that were treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-dC). RESULTS: DNA methylation profiling revealed 929 differentially methylated sites between normal and OA cartilage, comprising a total of 500 individual genes. Among these, 45 transcription factors that harbored differentially methylated sites were identified. Integrative analysis and subsequent validation showed a subset of 6 transcription factors that were significantly hypermethylated and down-regulated in OA cartilage (ATOH8, MAFF, NCOR2, TBX4, ZBTB16, and ZHX2). Upon 5-aza-dC treatment, TC28 cells showed a significant increase in gene expression for all 6 transcription factors. In primary chondrocytes, ATOH8 and TBX4 were increased after 5-aza-dC treatment. CONCLUSION: Our findings reveal that normal and OA knee articular cartilage have significantly different methylomes. The identification of a subset of epigenetically regulated transcription factors with reduced expression in OA may represent an important mechanism to explain changes in the chondrocyte transcriptome and function during OA pathogenesis. PMID- 26881701 TI - Phomopchalasins A and B, Two Cytochalasans with Polycyclic-Fused Skeletons from the Endophytic Fungus Phomopsis sp. shj2. AB - Phomopchalasins A (1) and B (2), two novel cytochalasans with unprecedented carbon skeletons, and phomopchalasin C (3), containing a rare hydroperoxyl motif, were obtained from the endophytic fungus Phomopsis sp. shj2, which was first isolated from the Isodon eriocalyx var. laxiflora. Their structures were elucidated by extensive spectroscopic analyses, electronic circular dichroism (ECD) calculation, and X-ray crystallographic analysis. Notably, 1 possessed an unprecedented 5/6/5/8-fused tetracyclic ring system, and 2 featured a novel 5/6/6/7/5-fused pentacyclic skeleton. The cytotoxic, anti-inflammatory, and antimigratory activities of 1-3 were evaluated in vitro. PMID- 26881703 TI - Hyderabad declaration 2014. PMID- 26881704 TI - Thermal Degradation and Isomerization of beta-Carotene in Oil-in-Water Nanoemulsions Supplemented with Natural Antioxidants. AB - The goal of this study was to see the impact on the retention and isomerization of encapsulated beta-carotene (BC) in nanoemulsions fortified with natural antioxidants (alpha-tocopherol (AT) and l-ascorbic acid (AA)). The physical stability of nanoemulsion, oxidative stability, and isomerization of all-trans beta-carotene (BC) in oil-in-water (O/W) nanoemulsions were determined in the presence or absence of natural antioxidants at 25 and 50 degrees C at certain intervals of time by high-performance liquid chromatography (HPLC). Sodium caseinate was used as the emulsifier, and corn oil (CO) was more protective than medium-chain triglycerides (MCT) and used for isomerization studies. Mean diameters of control (without antioxidants) and AA- and AT-fortified particles were similar. Mean particle diameter of nanoemulsions increased from 10 to 25 nm at 25 degrees C and from 40 to 50 nm at 50 degrees C during 30 days of storage. The isomerization from all-trans-BC to cis-BC isomers was inhibited by antioxidants. The isomerization rates were in the following order: 13-cis-BC > 15 cis-BC > 9-cis-BC. AT had better antioxidant activities than AA in inhibiting BC degradation in O/W nanoemulsions. The results indicated that BC encapsulated in nanoemulsions supplemented with antioxidants could significantly improve BC's chemical stability. PMID- 26881702 TI - Expression profile and overexpression outcome indicate a role for betaKlotho in skeletal muscle fibro/adipogenesis. AB - Regeneration of skeletal muscles is required throughout life to ensure optimal performance. Therefore, a better understanding of the resident cells involved in muscle repair is essential. Muscle repair relies on satellite cells (SCs), the resident myogenic progenitors, but also involves the contribution of interstitial cells including fibro/adipocyte progenitors (FAPs). To elucidate the role of the fibroblast growth factor (FGF) signaling in these two cell populations, we previously analyzed freshly isolated cells for their FGF receptor (FGFR) signature. Transcript analysis of the four Fgfr genes revealed distinct expression profiles for SCs and FAPs, raising the possibility that these two cell types have different FGF-mediated processes. Here, we pursued this hypothesis exploring the role of the Klotho genes, whose products are known to function as FGFR co-receptors for the endocrine FGF subfamily. Isolated SC and FAP populations were analyzed in culture, exhibiting spontaneous myogenic or adipogenic differentiation, respectively. alphaKlotho expression was not detected in either population. betaKlotho expression, while not detected in SCs, was strongly upregulated in FAPs entering adipogenic differentiation, coinciding with expression of a panel of adipogenic genes and preceding the appearance of intracellular lipid droplets. Overexpression of betaKlotho in mouse cell line models enhanced adipogenesis in NIH3T3 fibroblasts but had no effect on C2C12 myogenic cells. Our study supports a pro-adipogenic role for betaKlotho in skeletal muscle fibro/adipogenesis and calls for further research on involvement of the FGF-FGFR-betaKlotho axis in the fibro/adipogenic infiltration associated with functional deterioration of skeletal muscle in aging and muscular dystrophy. PMID- 26881706 TI - Are Human Tyrosinase and Related Proteins Suitable Targets for Melanoma Therapy? AB - Among the human copper-containing monooxygenases, Tyrosinase (Ty) is an important enzyme involved in the determinant step of the biosynthetic pathway of melanin pigment. In this pathway, Ty catalyzes the tyrosine monooxygenation into L-DOPA quinone, which is the precursor of the skin pigment melanin. Ty inhibitors/activators are a well-established approach for controlling in vivo melanin production, so their development has a huge economical and industrial impact. Moreover, recent publications highlight that targeting tyrosinase with inhibitors/activators to treat melanogenesis disorders is one of many possible approaches, due to the complex biochemical reaction involved in the melanin synthesis. PMID- 26881705 TI - Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite. AB - Malaria is one of the world's most devastating diseases, particularly in the tropics. In humans, Plasmodium falciparum lives mainly within red blood cells, and malaria pathogenesis depends on the red blood cells being infected with the parasite. Nonesterified fatty acids (NEFAs), including cis-9-octadecenoic acid, and phospholipids have been critical for complete parasite growth in serum-free culture, although the efficacy of NEFAs in sustaining the growth of P. falciparum has varied markedly. Hexadecanoic acid and trans-9-octadecenoic acid have arrested development of the parasite, in association with down-regulation of genes encoding copper-binding proteins. Selective removal of Cu+ ions has blockaded completely the ring-trophozoite-schizont progression of the parasite. The importance of copper homeostasis for the developmental progression of P. falciparum has been confirmed by inhibition of copper-binding proteins that regulate copper physiology and function by associating with copper ions. These data have provided strong evidence for a link between healthy copper homeostasis and successive developmental progression of P. falciparum. Perturbation of copper homeostasis may be, thus, instrumental in drug and vaccine development for the malaria medication. We review the importance of copper homeostasis in the asexual growth of P. falciparum in relation to NEFAs, copperbinding proteins, apoptosis, mitochondria, and gene expression. PMID- 26881707 TI - Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease. AB - Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn2+, this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn2+-binding, and hence affects the control of circulatory and cellular Zn2+ dynamics. This relationship between circulatory fatty acid and Zn2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states - including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metal-binding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn2+, its effect upon cellular Zn2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease. PMID- 26881708 TI - Bis(thiosemicarbazone) Metal Complexes as Therapeutics for Neurodegenerative Diseases. AB - Pathological aggregation of endogenous proteins is a common feature of many neurodegenerative diseases. This is generally accompanied by elevated levels of oxidative stress associated with transition metal dyshomeostasis. As such, strategies targeted toward rectifying metal imbalance are increasingly becoming an attractive therapeutic option. One class of compound showing such therapeutic potential are the bis(thiosemicarbazone) metal complexes. These are small, orally bioavailable compounds capable of crossing the blood brain barrier and capable of delivering bioavailable metal intracellularly. Members of this family of compounds have been shown to successfully treat animal models of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Here we review the current evidence for the efficacy of bis(thiosemicarbazone) metal complexes in treating these diseases and discuss the implications for future development of these compounds. PMID- 26881709 TI - Scaffold Repurposing of Old Drugs Towards New Cancer Drug Discovery. AB - As commented by the Nobelist James Black that "The most fruitful basis of the discovery of a new drug is to start with an old drug", drug repurposing represents an attractive drug discovery strategy. Despite the success of several repurposed drugs on the market, the ultimate therapeutic potential of a large number of non-cancer drugs is hindered during their repositioning due to various issues including the limited efficacy and intellectual property. With the increasing knowledge about the pharmacological properties and newly identified targets, the scaffolds of the old drugs emerge as a great treasure-trove towards new cancer drug discovery. In this review, we summarize the recent advances in the development of novel small molecules for cancer therapy by scaffold repurposing with highlighted examples. The relevant strategies, advantages, challenges and future research directions associated with this approach are also discussed. PMID- 26881710 TI - The Importance of Bioactivation in Computer-Guided Drug Repositioning. Why the Parent Drug is Not Always Enough. AB - Although bioactivation is a well-documented process and the role of active metabolites in the drug discovery field has long been recognized, drug metabolites are usually ignored in virtual screening campaigns oriented to drug repositioning. The present article discusses different issues related to overlooking of the active metabolites in virtual screening campaigns, including an overview of the essential aspects of drug biotransformation and a summary of computational approaches that can provide solutions to those issues. Some valuable computational resources connected with this topic are also overviewed. PMID- 26881711 TI - Repurposing Drugs for Cancer Prevention. AB - Development of agents for cancer prevention has been particularly challenging for two main reasons. One is the inherent difficulty in identifying targets for the heterogeneous group of processes that lead to invasive cancer arising at different target organ sites, while the other is the need for safe, tolerable interventions that can be given for lengthy periods of time. The rapidly increasing understanding of the molecular pathogenesis of cancer is providing new opportunities for early intervention, prior to the development of invasive disease. Furthermore, there is an ever-increasing number of approved drugs with many different mechanisms of action. The appeal of using drugs with well described mechanisms of action and safety profiles has led to renewed interest in repurposing such agents for cancer prevention. Here we review the rationale and evidence of effectiveness of three agents that are the current focus of much interest in the field of cancer prevention - aspirin, metformin, and pioglitazone. PMID- 26881712 TI - Revisiting Non-Cancer Drugs for Cancer Therapy. AB - Although tremendous effort has been made over the past century to treat cancer effectively, the pace of drug development is far behind the increasing rate of cancer incidence and mortality. There are two major hurdles in anticancer drug development: dose-limiting toxic side effects that reduce either drug effectiveness or the quality of life of patients and complicated drug development processes that are costly and time consuming. Drug repositioning has recently gained increasing attention among cancer researchers as this approach utilizes existing drugs and is significantly cost- and time-effective. Existing drugs, particularly non-cancer drugs, have favorable safety profiles in humans and serve as an ever-increasing source for new anticancer drug discovery. Here we review the recent examples of drug repositioning of existing non-cancer drugs for preclinical and clinical introductions of cancer therapy. PMID- 26881713 TI - Neglected Tropical Protozoan Diseases: Drug Repositioning as a Rational Option. AB - Neglected tropical diseases represent a major sanitary problem and a huge economic burden to endemic countries, and are currently expanding to non-endemic countries owing to migration currents. Though long abandoned in the past, recent research on novel therapeutics has already started to show results. Drug repositioning is one of the prominent, more successful strategies to approach the development of new treatments for these diseases. Here we present an overview on the limitations of the current available medications to treat African trypanosomiasis, Chagas disease and Leishmaniasis, along with a review on drug candidates presently undergoing clinical trials and drug candidates identified through drug repositioning initiatives. PMID- 26881714 TI - Irreversible LSD1 Inhibitors: Application of Tranylcypromine and Its Derivatives in Cancer Treatment. AB - Due to the increasing costs and time consuming for new drug discovery, a large number of pharmaceutical firms have chosen to modify the existing drug molecules for repositioning candidates with new or improved properties, especially those with severe adverse effects, thereby accelerating the drug discovery process. Such strategy has witnessed its success with several examples reported. As the first identified histone lysine specific demethylase, lysine specific demethylase 1 (LSD1) is classified as a member of monoamine oxidase (MAO) superfamily, and specifically removes mono- and dimethylated histone 3 lysine 4 (H3K4) and H3 lysine 9 (H3K9). It has been reported that LSD1 and its downstream targets are involved in cancer cell growth and metastasis. Meanwhile, it is overexpressed in a variety of tumor cells. Inactivating LSD1 specifically inhibits tumor progression and metastasis. Hence, LSD1 inhibition may represent a new and promising direction in anti-cancer drug discovery. Based on the structure and cofactor of LSD1, some clinical applied MAO inhibitors have been identified as LSD1 inactivators. Among them, tranylcypromine presented the most potency against LSD1 and its derivatives were further developed by medicinal chemists in order to develop potent and selective LSD1 inhibitors. Currently, a number of tranylcypromine based LSD1 inhibitors have been developed and two of them, ORY 1001 and GSK2879552, are in clinical trials for cancer treatment. This review highlights recent advances in the repurposing of tranylcypromine and its derivatives as irreversible LSD1 inhibitors for cancer treatment, which are conventionally used for the treatment of depression. PMID- 26881715 TI - An Insight into Drug Repositioning for the Development of Novel Anti-Cancer Drugs. AB - Increased investments and development of new technologies in drug discovery have barely improved the outcome of medicinal entities in the drug discovery market from a long time. Minimal success rates of drug approvals, poor safety profiles, and long development processes are some of many hurdles encountered in the drug discovery field. Therefore, drug repurposing can provide an alternative approach to meet the demands of the new, potent and safe anti-cancer agents in terms of both economic cost and time efficiency. The common molecular pathways of different diseases and secondary indications of most of the approved drugs, and advances in genomics, informatics and biology, as well as the availability of approved or safe drug libraries can certainly provide an improved and efficient way of screening safer drugs for new indications. Promising results of drug repurposing in different therapeutic areas have encouraged the scientific community to discover new drugs for different diseases using this methodology. Herein, we provide a general overview of structurally and functionally diverse approved drugs that have been repurposed as anti-cancer drugs. PMID- 26881716 TI - The Repurposing of Old Drugs or Unsuccessful Lead Compounds by in Silico Approaches: New Advances and Perspectives. AB - Have you a compound in your lab, which was not successful against the designed target, or a drug that is no more attractive? The drug repurposing represents the right way to reconsider them. It can be defined as the modern and rationale approach of the traditional methods adopted in drug discovery, based on the knowledge, insight and luck, alias known as serendipity. This repurposing approach can be applied both in silico and in wet. In this review we report the molecular modeling facilities that can be of huge support in the repurposing of drugs and/or unsuccessful lead compounds. In the last decades, different methods were proposed to help the scientists in drug design and in drug repurposing. The steps strongly depend on the approach applied. It could be a ligand or a structure based method, correlated to the use of specific means. These processes, starting from a compound with potential therapeutic properties and a sizeable number of toxicity passed tests, can successfully speed up the very slow development of a molecule from bench to market. Herein, we discuss the facilities available to date, classifying them by methods and types. We have reported a series of databases, ligand and structure stand-alone software, and of web-based tools, which are free accessible to scientific community. This review does not claim to be exhaustive, but can be of interest to help in drug repurposing through in silico methods, as a valuable tool for the medicinal chemistry community. PMID- 26881717 TI - Computational Drug Repositioning: A Lateral Approach to Traditional Drug Discovery? AB - Computational drug repositioning is popular in academia and pharmaceutical industry globally. The repositioning hypotheses, generated using a variety of computational methods, can be quickly tested experimentally. Several success stories have emerged in the past decade or so. Newer concepts and methods such as drug profile matching are being tried to address the limitations of current computational repositioning methods. The trend is shifting from earlier small scale to large-scale or global-scale repositioning applications. Other related approaches such as prediction of molecular targets for novel molecules, prediction of side-effect profiles of new molecular entities (NMEs), etc., are applied routinely. The current article focuses on state-of-the-art of computational drug repositioning field with the help of relevant examples and case studies. This 'lateral' approach has significant potential to bring down the time and cost of the awfully expensive drug discovery research and clinical development. The persistence and perseverance in the successful application of these methods is likely to be paid off in near future. PMID- 26881718 TI - Reprofiling of Troglitazone Towards More Active and Less Toxic Derivatives: A New Hope for Cancer Treatment? AB - The existence of unresponsive tumors and the appearance of resistant tumors during the course of treatments both justify that we increase urgently the panel of pharmacological molecules able to fight cancer. An interesting strategy is drug reprofiling (also known as drug repositioning, drug repurposing or drug retasking) that consists of identifying and developing new uses for existing drugs. This review illustrates drug reprofiling with troglitazone (TGZ), a synthetic PPARgamma agonist initially used for the treatment of type II diabetes. The fact that TGZ also displays anticancer effects is known since the end of the nineties but its development as an anticancer agent was slowed down due to hepatotoxic side effects. Part of the knowledge available for TGZ, mainly the molecular basis for PPARgamma activation, its metabolization pathways and the side effects on hepatocytes, were taken into account to elaborate new molecules. Key findings were that unsaturated TGZ derivatives, when compared to TGZ, do not activate PPARgamma, exhibit a higher efficiency on cancer cells and a lower toxicity towards hepatocytes. However, a weakness is that the mechanisms involved in the anticancer effects are still not completely understood and that the efficiency of such derivatives has not yet been completely studied in vivo. Data about this point should become available very soon from animal models and this will be a prerequisite to initiate clinical trials with these potential new anticancer drugs developed from a drug repurposing strategy. PMID- 26881719 TI - Repositioning of DHFR Inhibitors. AB - Development of new drugs is a time-consuming, hugely expensive and an uncertain endeavor. The pharmaceutical industry is looking for cost-effective alternatives with reduced risks of drug failure. Validated target machinery along with established inhibitors indicates usefulness in drug design, discovery and further development. Folate metabolism, found in both prokaryotes and eukaryotes, represents an essential druggable target for chemotherapy. Numerous enzymes in the cell replication cycle use folate either as a cofactor or as a substrate. DHFR, an enzyme of the folate biosynthesis pathway is an established chemotherapeutic target, initially explored for anti-cancer drug discovery. Diaminopteridines e.g. methotrexate and aminopterin, primarily used as anti cancer agents, are folic acid analogues, first reported in late 1940's, used to produce temporary remission of acute leukaemia in children. However, due to the toxicity of these drugs, they could not be used for other therapeutic implications such as in the treatment of infectious diseases. Development of newer diaminopteridine derivatives has helped in repositioning their therapeutic usefulness. These analogues have now been proven as anti-parasitic, immuno suppressants, anti-bacterial agents, to enlist a few therapeutic applications. Likewise, diaminopyrimidine, diaminoquinazoline and diaminodihydrotriazines are being explored for structural modifications by which they can be repurposed from their originally developed medicinal applicability and exploited for various other infectious disease conditions. In this review, we encompass the study of DHFR inhibitors potentially to be repurposed for different infectious disease case scenario and also highlight the novel anti-infective drug discovery benefits therein. PMID- 26881720 TI - Metformin - The Drug for the Treatment of Autoimmune Diseases; A New Use of a Known Anti-Diabetic Drug. AB - Autoimmune diseases are characterized by the production of autoantibodies directed against specific organs of own organism. Additional common traits of autoimmune diseases are chronic inflammation due to generation of inflammatory mediators, and disorders of redox processes. The pathogenesis of autoimmune diseases is still unknown. Treatment is based only on relieving the symptoms and improving the quality of patients lives. Metformin, which is used in treatment of type 2 diabetes, has properties which are desirable for autoimmune disease therapy, including anti-inflammatory and antioxidant effects, and the ability to regenerate the endothelium. PMID- 26881721 TI - Repositioning of Drugs in Cardiometabolic Disorders: Importance and Current Scenario. AB - Cardiometabolic disorder (CMD) is a cluster of diseases, including cardiovascular diseases (CVDs), metabolic syndrome (MS) and diabetes mellitus (DM). Cardiometabolic disorders (CMDs) remain the principal cause of death in both developed and developing countries, accounting for nearly 32% of all deaths worldwide per year. In addition, dyslipidemia, angina, arrhythmia, cardiac failure, myocardial infarction (MI), and diabetes mellitus represent the leading killer with an estimated 19 million people died from CMDs in 2012. By 2030 more than 23 million people will die annually from CVDs. Existing drugs are not efficient enough to reduce the disease burden as well as mortality. Therefore, there is an urgent demand for new drugs in this area to reduce the mortality and control the associated disability. Nonetheless, new drug discovery (NDD) in CMDs has become more challenging for last couple of decades due to increased expenses and decreased success rate. In such a scenario, drug repositioning in the CMDs appears promising for introducing existing drugs for new therapeutic indication. Repositioning is quite an old strategy dating back to 1960s and mainly followed by serendipitous observations during clinical use of drugs. A major advantage of repositioning is that the safety profile of the drug is well established thus reducing the chances of failure due to adverse toxic effects. In addition, repositioning requires less time and investment than NDD. Considering these facts, pharmaceutical companies are now becoming increasingly interested in drug repositioning. In this follow-up, we have talked about the concept of repositioning with important examples of repositioned drugs in cardiometabolic disorder. PMID- 26881722 TI - The Role of Spin-Orbit Coupling in the Double-Ionization Photoelectron Spectra of XCN(2+) (X = Cl, Br, and I). AB - The photoelectron spectra of XCN(2+) (X = Cl, Br, and I) were calculated employing ab initio electronic structure methods with high-level electron correlation and explicit treatment of spin-orbit coupling. Twelve scalar relativistic excited states of the dicationic systems, calculated from state averaged CASSCF/MRCI calculations, were used as the electronic basis to evaluate spin-orbit eigenstates. While the spin-orbit effects in ClCN(2+) are found to be negligible, the electronic spectroscopy of BrCN(2+) and ICN(2+) is significantly influenced by interstate spin-orbit coupling. Several electronic degeneracies are lifted, and many unexpected accidental degeneracies occurred due to the spin orbit coupling. In particular, the spin-orbit interactions between X (3)Sigma(-) b (1)Sigma(+), A (3)Pi-c (1)Pi, B (3)Delta-a (1)Delta, and C (3)Sigma(+)-d (1)Sigma(-) are found to be strong in BrCN(2+) and ICN(2+). By careful analysis of the effect of spin-orbit coupling parameters and the spin-orbit eigenstate composition, an assignment of the hitherto unidentified experimental photoelectron bands of BrCN(2+) and ICN(2+) is presented. PMID- 26881723 TI - Spin-State Versatility in a Series of Fe4 [2 * 2] Grid Complexes: Effects of Counteranions, Lattice Solvent, and Intramolecular Cooperativity. AB - The new compartmental proligand 4-bromo-3,5-bis{6-(2,2'-bipyridyl)}pyrazole (HL(Br)) was synthesized and shown to form robust [2 * 2] grid complexes [Fe(II)4L(Br)4]X4 with various counteranions (X(-) = PF6(-), ClO4(-), BF4(-), Br( )). The grid [Fe(II)4L(Br)4](4+) is stable in solution and features two high-spin (HS) and two low-spin (LS) ferrous ions in frozen MeCN, and its redox properties have been studied. Six all-ferrous compounds [Fe4L(Br)4]X4 with different counteranions and different lattice solvent (1a-f) were structurally characterized by X-ray diffraction, and their magnetic properties were investigated by Mossbauer spectroscopy and SQUID magnetometry. Variations in spin state for the crystalline material range from the [4HS] via the [3HS-1LS] to the [2HS-2LS] forms, with some grids showing thermal spin crossover (SCO). The series of [Fe(II)4L(Br)4](4+) compounds allowed us to establish experimentally well grounded correlations between structural distortion of the {FeN6} coordination polyhedra, quantified by using continuous shape measures, and the grid's spin state pattern. These correlations evidenced pronounced cooperativity for the multistep SCO transitions within the grid, imparted by the strain effects of the rigid bridging ligands, and a high stability of the dimixed-spin configuration trans-[2HS-2LS] that has identical sites at opposite corners of the grid. The results are in good agreement with recent quantum chemical calculations for such molecular [2 * 2] grids featuring strongly elastically coupled vertices. PMID- 26881724 TI - Trapping Methylglyoxal by Genistein and Its Metabolites in Mice. AB - Increasing evidence supports dicarbonyl stress such as methylglyoxal (MGO) as one of the major pathogenic links between hyperglycemia and diabetic complications. In vitro studies have shown that dietary flavonoids can inhibit the formation of advanced glycation end products (AGEs) by trapping MGO. However, whether flavonoids can trap MGO in vivo and whether biotransformation limits the trapping capacity of flavonoids remain virtually unknown. In this study, we investigated whether genistein (GEN), the major soy isoflavone, could trap MGO in mice by promoting the formation of MGO adducts of GEN and its metabolites. Two different mouse studies were conducted. In the acute study, a single dose of MGO and GEN were administered to mice via oral gavage. In the chronic study, MGO was given to mice in drinking water for 1 month and then GEN was given to mice for 4 consecutive days via oral gavage. Two mono-MGO adducts of GEN and six mono-MGO adducts of GEN phase I and microbial metabolites were identified in mouse urine samples from these studies using liquid chromatography/electrospray ionization tandem mass spectrometry. The structures of these MGO adducts were confirmed by analyzing their MS(n) (n = 1-4) spectra as well as by comparing them with the tandem mass spectra of authentic standards. All of the MGO adducts presented in their phase II conjugated forms in mouse urine samples in the acute and chronic studies. To our knowledge, this is the first in vivo evidence to demonstrate the trapping efficacy of GEN in mice and to show that the metabolites of GEN remain bioactive. PMID- 26881725 TI - An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi. AB - Although NMR in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. Time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or IC50 value was obtained. Applications to spermidine synthase of Trypanosoma cruzi, which causes Chagas disease, are described. PMID- 26881726 TI - Probing Defects and Correlations in the Hydrogen-Bond Network of ab Initio Water. AB - The hydrogen-bond network of water is characterized by the presence of coordination defects relative to the ideal tetrahedral network of ice, whose fluctuations determine the static and time-dependent properties of the liquid. Because of topological constraints, such defects do not come alone but are highly correlated coming in a plethora of different pairs. Here we discuss in detail such correlations in the case of ab initio water models and show that they have interesting similarities to regular and defective solid phases of water. Although defect correlations involve deviations from idealized tetrahedrality, they can still be regarded as weaker hydrogen bonds that retain a high degree of directionality. We also investigate how the structure and population of coordination defects is affected by approximations to the interatomic potential, finding that, in most cases, the qualitative features of the hydrogen-bond network are remarkably robust. PMID- 26881727 TI - Effects of soil management techniques on soil water erosion in apricot orchards. AB - Soil erosion is extreme in Mediterranean orchards due to management impact, high rainfall intensities, steep slopes and erodible parent material. Vall d'Albaida is a traditional fruit production area which, due to the Mediterranean climate and marly soils, produces sweet fruits. However, these highly productive soils are left bare under the prevailing land management and marly soils are vulnerable to soil water erosion when left bare. In this paper we study the impact of different agricultural land management strategies on soil properties (bulk density, soil organic matter, soil moisture), soil water erosion and runoff, by means of simulated rainfall experiments and soil analyses. Three representative land managements (tillage/herbicide/covered with vegetation) were selected, where 20 paired plots (60 plots) were established to determine soil losses and runoff. The simulated rainfall was carried out at 55mmh(-1) in the summer of 2013 (<8% soil moisture) for one hour on 0.25m(2) circular plots. The results showed that vegetation cover, soil moisture and organic matter were significantly higher in covered plots than in tilled and herbicide treated plots. However, runoff coefficient, total runoff, sediment yield and soil erosion were significantly higher in herbicide treated plots compared to the others. Runoff sediment concentration was significantly higher in tilled plots. The lowest values were identified in covered plots. Overall, tillage, but especially herbicide treatment, decreased vegetation cover, soil moisture, soil organic matter, and increased bulk density, runoff coefficient, total runoff, sediment yield and soil erosion. Soil erosion was extremely high in herbicide plots with 0.91Mgha(-1)h( 1) of soil lost; in the tilled fields erosion rates were lower with 0.51Mgha( 1)h(-1). Covered soil showed an erosion rate of 0.02Mgha(-1)h(-1). These results showed that agricultural management influenced water and sediment dynamics and that tillage and herbicide treatment should be avoided. PMID- 26881728 TI - Valuing the benefits of improved marine environmental quality under multiple stressors. AB - Many marine ecosystems are under increasing pressure from multiple stressors. In the Baltic Sea, these stressors include oil and chemical spills from shipping, nutrient run-off from land and the introduction of non-indigenous species. All of these pressures have been growing over recent years. Increasing pressures lead to reductions in environmental quality, which produce negative effects on human well being. In this paper, the choice experiment method is used to estimate the benefits to people in Estonia resulting from reductions in pressure from multiple stressors in the Baltic Sea. The main results show that, firstly, respondents have a positive, statistically-significant willingness to pay to reduce each of the three stressors analysed. Secondly, the average willingness to pay for the improvement in the quality of all Estonian marine waters to achieve Good Environmental Status is around 65 euro per household per year, with a 95% confidence interval of 48-77 euro. Thirdly, the greatest share of value of this total economic benefit is derived from the willingness to pay for reductions in the risk of large scale oil and chemical spills. PMID- 26881729 TI - Using spatially explicit indicators to investigate watershed characteristics and stream temperature relationships. AB - We generate a series of novel indicators of spatially explicit watershed permeability and runoff characteristics to examine the relationship between land cover and water temperature parameters in a rapidly urbanizing watershed. Our framework provides a readily adaptable method to examine the thermal sensitivity of streams based upon the underlying geomorphological and surface characteristics of drainage basins. Using four model groups each using a different landscape characteristic weighting scheme (Model Group 1: areal averages; Model Group 2: inverse distance by total flow length; Model Group 3: overland distance to stream network and distance squared; Model Group 4: proportional flow accumulation), we examined the predictive capacity of 19 variables, including combinations of simplified land cover, elevation, slope, and flow accumulation, on five stream thermal properties: seven day moving average of daily minimum and maximum, seasonal mean temperature, a novel metric of thermal 'flashiness', and total days with maximum temperature exceeding 17.8 degrees C. We find that the use of spatially explicit landscape indicators combining watershed processes improves the performance of regressions for predicting a number of ecologically relevant stream temperature variables. Improved indicators of watershed condition lend themselves for rapid investigation of the relationship between stream thermal conditions and landscape characteristics in watersheds modified by human land uses, ultimately providing a more hydrologically meaningful indicator for the impacts of landscape change. PMID- 26881730 TI - Change in hydrophilicity of penicillins during advanced oxidation by radiolytically generated OH compromises the elimination of selective pressure on bacterial strains. AB - Advanced oxidation processes are promising technologies for removal of antibiotic residues from wastewater in terms of their high efficacy. However, recent studies have reported the remaining antibacterial activity of the products at early stages of treatment. The present study investigates the effect of such products of model beta-lactams (amoxicillin, ampicillin, cloxacillin) on bacteria introducing structure-based, and biological approaches involving Gram-positive and Gram-negative bacterial strains. Chemical analysis revealed the destruction of the beta-lactam pharmacophore in competition with the reaction at the aromatic ring. Multisite attack occurs on the penicillin skeleton producing OH-substituted products. The enhanced hydrophilicity confers higher diffusion rate through the porin channels of Gram-negative bacteria and through the hydrophilic cell wall of Gram-positive species. Accordingly, an increase in acute toxicity of treated samples was observed at the beginning of the treatment. The same tendency was observed for target-specific antimicrobial activity investigated with antibiotic susceptibility testing (agar-diffusion, bacterial growth). Prolonged treatments yielded products, e.g. polyhydroxylated phenolic compounds, being also deleterious for bacteria. Therefore, the advanced oxidation process should be judiciously optimized. PMID- 26881732 TI - Dynamic exchanges between DOM and POM pools in coastal and inland aquatic ecosystems: A review. AB - Dynamic exchanges between dissolved organic matter (DOM) and particulate organic matter (POM) plays a critical role in organic carbon cycling in coastal and inland aquatic ecosystems, interactions with aquatic organisms, mobility and bioavailability of pollutants, among many other ecological and geochemical phenomena. Although DOM-POM exchange processes have been widely studied from different aspects, little to no effort has been made to date to provide a comprehensive, mechanistic, and micro-spatial schema for understanding various exchange processes occurring in different aquatic ecosystems in a unified way. The phenomena occurring between DOM and POM were explained here with the homogeneous and heterogeneous mechanisms. In the homogeneous mechanism, the participating components are only organic matter (OM) constituents themselves with aggregation and dissolution involved, whereas OM is associated with other components such as minerals and particulate colloids in the heterogeneous counterpart. Besides the generally concerned processes of aggregation/dissolution and adsorption/desorption, other ecological factors such as sunlight and organisms can also participate in DOM-POM exchanges through altering the chemical nature of OM. Despite the limitation of current analytical technologies, many unknown and/or unquantified processes need to be identified to unravel the complicated exchanges of OM between its dissolved and particulate states. Based on the review of several previous mathematical models, we proposed a unified conceptual model to describe all major dynamic exchange mechanisms on the basis of exergy theory. More knowledge of dynamic DOM-POM exchanges is warranted to overcome the potential problems arising from a simple division of OM into dissolved versus particulate states and to further develop more sophisticated mathematic models. PMID- 26881731 TI - Conservation of the Ethiopian church forests: Threats, opportunities and implications for their management. AB - In the central and northern highlands of Ethiopia, native forest and forest biodiversity is almost confined to sacred groves associated with churches. Local communities rely on these 'church forests' for essential ecosystem services including shade and fresh water but little is known about their region-wide distribution and conservation value. We (1) performed the first large-scale spatially-explicit assessment of church forests, combining remote-sensing and field data, to assess the number of forests, their size, shape, isolation and woody plant species composition, (2) determined their plant communities and related these to environmental variables and potential natural vegetation, (3) identified the main challenges to biodiversity conservation in view of plant population dynamics and anthropogenic disturbances, and (4) present guidelines for management and policy. The 394 forests identified in satellite images were on average ~2ha in size and generally separated by ~2km from the nearest neighboring forest. Shape complexity, not size, decreased from the northern to the central highlands. Overall, 148 indigenous tree, shrub and liana species were recorded across the 78 surveyed forests. Patch alpha-diversity increased with mean annual precipitation, but typically only 25 woody species occurred per patch. The combined results showed that >50% of tree species present in tropical northeast Africa were still present in the 78 studied church forests, even though individual forests were small and relatively species-poor. Tree species composition of church forests varied with elevation and precipitation, and resembled the potential natural vegetation. With a wide distribution over the landscape, these church forests have high conservation value. However, long-term conservation of biodiversity of individual patches and evolutionary potential of species may be threatened by isolation, small sizes of tree species populations and disturbance, especially when considering climate change. Forest management interventions are essential and should be supported by environmental education and other forms of public engagement. PMID- 26881733 TI - Pathogens and fecal indicators in waste stabilization pond systems with direct reuse for irrigation: Fate and transport in water, soil and crops. AB - Wastewater use for irrigation is expanding globally, and information about the fate and transport of pathogens in wastewater systems is needed to complete microbial risk assessments and develop policies to protect public health. The lack of maintenance for wastewater treatment facilities in low-income areas and developing countries results in sludge accumulation and compromised performance over time, creating uncertainty about the contamination of soil and crops. The fate and transport of pathogens and fecal indicators was evaluated in waste stabilization ponds with direct reuse for irrigation, using two systems in Bolivia as case studies. Results were compared with models from the literature that have been recommended for design. The removal of Escherichia coli in both systems was adequately predicted by a previously-published dispersed flow model, despite more than 10years of sludge accumulation. However, a design equation for helminth egg removal overestimated the observed removal, suggesting that this equation may not be appropriate for systems with accumulated sludge. To assess the contamination of soil and crops, ratios were calculated of the pathogen and fecal indicator concentrations in soil or on crops to their respective concentrations in irrigation water (termed soil-water and crop-water ratios). Ratios were similar within each group of microorganisms but differed between microorganism groups, and were generally below 0.1mLg(-1) for coliphage, between 1 and 100mLg(-1) for Giardia and Cryptosporidium, and between 100 and 1000mLg(-1) for helminth eggs. This information can be used for microbial risk assessments to develop safe water reuse policies in support of the United Nations' 2030 Sustainable Development Agenda. PMID- 26881734 TI - Pridopidine for the treatment of Huntington's disease. AB - INTRODUCTION: Huntington's disease is a rare dominantly-inherited neurodegenerative disease with motor, cognitive and behavioral manifestations. It results from an expanded unstable trinucleotide repeat in the coding region of the huntingtin gene. Treatment is symptomatic, but a poor evidence baseguides selection of therapeutic agents. Non-choreic derangements in voluntary movement contribute to overall motor disability and are poorly addressed by current therapies. Pridopidine is a novel agent in the dopidine class believed to have 'state dependent' effects at dopamine receptors, thus show promise in the treatment of these disorders of voluntary movement. AREAS COVERED: This review discusses the pharmacokinetics and pharmacodynamics of pridopidine and reviews clinical trials supporting development of the drug for HD. This information was culled from literature searches for dopidines, pridopidine, and HD experimental therapeutics in PubMed and at http://www.clinicaltrials.org . EXPERT OPINION: There is a compelling need to discover new treatments for motor disability in HD, particularly for non-choreic motor symptoms. While pridopidine failed to achieve its primary efficacy outcomes in 2 large trials, reproducible effects on secondary motor outcomes have fueled an ongoing trial studying higher doses and more focused clinical endpoints. This and phase III trials will define define the utility of pridopidine for HD. PMID- 26881735 TI - Ameliorative potential of fluoxetine/raloxifene combination on experimentally induced breast cancer. AB - Breast cancer is one of the most common types of malignancies in females worldwide. Targeting the estrogen receptors alone with raloxifene (RAL) reduces the incidence of estrogen receptor positive tumors. Fluoxetine (FLX) is one of selective serotonin reuptake inhibitors that was proven to have anticancer properties. Our aim was to detect the effects of RAL/FLX combination on experimentally induced breast cancer. Eighty female Wistar rats were divided into four equal groups: 7,12-Dimethyl Benzanthracene (DMBA) induced breast cancer group, DMBA+RAL, DMBA+FLX and DMBA+RAL+FLX. Tumor volume, tissue malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and transforming growth factor beta1 (TGF beta1) were determined in the tumor tissues. Parts of the tumor were subjected to histopathological examination. RAL or FLX alone or in combination induced significant increase in tumor CAT and SOD with significant decrease in tumor volume, tissue MDA, TNF-alpha, IL-6 and TGF-beta1 and alleviated the histopathological and immunohistochemical changes compared to DMBA group. In conclusion, RAL/FLX combination had a better effect than each of RAL or FLX alone against DMBA-induced breast cancer in rats which may represent a new therapeutic modality for management of breast cancer. PMID- 26881736 TI - Ultrastructural study of the spermatozoon of Hemiurus appendiculatus (Digenea, Hemiuroidea, Hemiuridae), a parasite of Boops boops (Pisces, Teleostei, Sparidae) off Senegal. AB - The mature spermatozoon of Hemiurus appendiculatus exhibits the general pattern described in most of the digenean namely, two axonemes of the 9 + "1" pattern of the Trepaxonemata, a nucleus, a filiform mitochondrion, external ornamentations of the plasma membrane and parallel cortical microtubules located on one side of the spermatozoon. In this study, we show for the second time in a digenean spermatozoon the presence of microtubules of the second axoneme associated each in a short length with an external ornamentation, seven cortical microtubules, a terminal bulge in the anterior spermatozoon extremity separate from the remainder of the spermatozoon by a transverse constriction and the simultaneous presence of the external ornamentation of the plasma membrane with a filamentous ornamentation. The external ornamentations have a differentiated distribution, cover almost the anterior region of the spermatozoon, are more abundant around the first axoneme and extend backwards over a short distance around the second axoneme. This study also allowed us to reveal for the first time the existence in the Hemiuroidea of an axoneme that begins to disrupt before reaching the front end of the mitochondrion. PMID- 26881737 TI - Determination of Protein Thiol Reduction Potential by Isotope Labeling and Intact Mass Measurement. AB - Oxidation/reduction of thiol residues in proteins is an important type of post translational modification that is implicated in regulating a range of biological processes. The nature of the modification makes it possible to define a quantifiable electrochemical potential (E(?)) for oxidation/reduction that allows cysteine-containing proteins to be ranked based on their propensity to be oxidized. Measuring oxidation of cysteine residues in proteins is difficult using standard electrochemical methods, but top-down mass spectrometry recently has been shown to enable the quantification of E(?) for thiol oxidations. In this paper, we demonstrate that mass spectrometry of intact proteins can be used in combination with an isotopic labeling strategy and an automated data analysis algorithm to measure E(?) for the thiols in both E. coli Thioredoxin 1 and human Thioredoxin 1. Our methodology relies on accurate mass measurement of proteins using liquid chromatography-mass spectroscopy (LC-MS) analyses and does not necessarily require top-down fragmentation. In addition to analyzing homogeneous protein samples, we also demonstrate that our methodology can be used to determine thiol E(?) measurements in samples that contain mixtures of proteins. Thus, the combination of experimential methodology and data analysis regime has the potential to make such measurements in a high-throughput manner and in a manner that is more accessible to a broad community of protein scientists. PMID- 26881738 TI - Bacterial diversity of floor drain biofilms and drain waters in a Listeria monocytogenes contaminated food processing environment. AB - Sanitation protocols are applied on a daily basis in food processing facilities to prevent the risk of cross-contamination with spoilage organisms. Floor drain water serves along with product-associated samples (slicer dust, brine or cheese smear) as an important hygiene indicator in monitoring Listeria monocytogenes in food processing facilities. Microbial communities of floor drains are representative for each processing area and are influenced to a large degree by food residues, liquid effluents and washing water. The microbial communities of drain water are steadily changing, whereas drain biofilms provide more stable niches. Bacterial communities of four floor drains were characterized using 16S rRNA gene pyrosequencing to better understand the composition and exchange of drain water and drain biofilm communities. Furthermore, the L. monocytogenes contamination status of each floor drain was determined by applying cultivation independent real-time PCR quantification and cultivation-dependent detection according to ISO11290-1. Pyrosequencing of 16S rRNA genes of drain water and drain biofilm bacterial communities yielded 50,611 reads, which were clustered into 641 operational taxonomic units (OTUs), affiliated to 16 phyla dominated by Proteobacteria, Firmicutes and Bacteroidetes. The most abundant OTUs represented either product- (Lactococcus lactis) or fermentation- and food spoilage associated phylotypes (Pseudomonas mucidolens, Pseudomonas fragi, Leuconostoc citreum, and Acetobacter tropicalis). The microbial communities in DW and DB samples were distinct in each sample type and throughout the whole processing plant, indicating the presence of indigenous specific microbial communities in each processing compartment. The microbiota of drain biofilms was largely different from the microbiota of the drain water. A sampling approach based on drain water alone may thus only provide reliable information on planktonic bacterial cells but might not allow conclusions on the bacterial composition of the microbiota in biofilms. PMID- 26881739 TI - Genital Self-Image and Considerations of Elective Genital Surgery. AB - The present study explores how genital self-image may be related to considerations of surgically altering one's genitals and documents the wanted genital changes among young adults. Evidence of a nontrivial proportion of respondents (98 of 1,110) had seriously considered elective genital surgery. Regression models indicate that, for both men and women, identifying as heterosexual and reporting lower composite genital self-image scores results in higher odds of considering genital surgery. Additionally for men, feeling unsatisfied with penis size increased the odds. Clinical and educational efforts to normalize and celebrate genital variation may influence considerations for genital modification in young adults. PMID- 26881740 TI - Predicting human intestinal absorption of diverse chemicals using ensemble learning based QSAR modeling approaches. AB - Human intestinal absorption (HIA) of the drugs administered through the oral route constitutes an important criterion for the candidate molecules. The computational approach for predicting the HIA of molecules may potentiate the screening of new drugs. In this study, ensemble learning (EL) based qualitative and quantitative structure-activity relationship (SAR) models (gradient boosted tree, GBT and bagged decision tree, BDT) have been established for the binary classification and HIA prediction of the chemicals, using the selected molecular descriptors. The structural diversity of the chemicals and the nonlinear structure in the considered data were tested by the similarity index and Brock Dechert-Scheinkman statistics. The external predictive power of the developed SAR models was evaluated through the internal and external validation procedures recommended in the literature. All the statistical criteria parameters derived for the performance of the constructed SAR models were above their respective thresholds suggesting for their robustness for future applications. In complete data, the qualitative SAR models rendered classification accuracy of >99%, while the quantitative SAR models yielded correlation (R(2)) of >0.91 between the measured and predicted HIA values. The performances of the EL-based SAR models were also compared with the linear models (linear discriminant analysis, LDA and multiple linear regression, MLR). The GBT and BDT SAR models performed better than the LDA and MLR methods. A comparison of our models with the previously reported QSARs for HIA prediction suggested for their better performance. The results suggest for the appropriateness of the developed SAR models to reliably predict the HIA of structurally diverse chemicals and can serve as useful tools for the initial screening of the molecules in the drug development process. PMID- 26881741 TI - MnO Conversion in Li-Ion Batteries: In Situ Studies and the Role of Mesostructuring. AB - Complex manganese oxides have been extensively studied as intercalation Li-ion battery electrodes. The simple oxide MnO has been proposed as a conversion anode material with a theoretical capacity of 756 mAh g(-1) for full reduction to the metal. We report the reaction of MnO with Li using in situ X-ray diffraction and find no sign of crystalline products upon either discharge or charge. However, the absence of reflections, paired with electrochemical impedance spectroscopy, suggests disordered discharge products. We also examine composite electrodes with porous particles of MnO as the active component, with pores generated through the reductive heating of Mn3O4. We compare the behavior of these with more dense MnO powders, including studies of the electrode morphologies pre- and postcyling. We find differences in the first discharge relevant to the utility of such mesostructuring in conversion reaction materials. Specifically, we find this type of mesostructure, which gives advantage in intercalation and pseudocapacitive storage, does not yield the same benefits for conversion reaction systems. PMID- 26881742 TI - Judgment and classification of emotion terms by older and younger adults. AB - OBJECTIVES: Theoretical models of adult development suggest changes in emotion systems with age. This study determined how younger and older adults judged and classified 70 emotion terms that varied in valence and arousal, and that have been used in previous studies of adult aging and emotion. The terms were from the Positive and Negative Affect Schedule - Expanded (PANAS-X) and the (KS) affect scales. METHOD: Older (n = 32) and younger adults (n = 111) engaged in a card sort task which determined how the 70 emotion terms were classified (i.e. grouped) in relation to one another. Activation and valence ratings of emotion terms were collected. RESULTS: There were 17 age group differences in item ratings for activation and 19 for valence. Older adults tended to rate emotion terms and scales as more positive and activating than younger persons. Card sort data indicated similarity in conceptualizations of emotion terms across groups with exceptions for serene, sad, and lonely. CONCLUSIONS: Research that utilizes self-report emotion data from older and younger persons should consider how perceptions of emotion terms may vary systematically with age. The constructs of sadness, loneliness, and serene may be age-variant and necessitate age-based adjustments in assessment and intervention. Further, older adults may perceive some emotion terms to be more activating and positive than younger persons. PMID- 26881743 TI - Adaptive Control of Exoskeleton Robots for Periodic Assistive Behaviours Based on EMG Feedback Minimisation. AB - In this paper we propose an exoskeleton control method for adaptive learning of assistive joint torque profiles in periodic tasks. We use human muscle activity as feedback to adapt the assistive joint torque behaviour in a way that the muscle activity is minimised. The user can then relax while the exoskeleton takes over the task execution. If the task is altered and the existing assistive behaviour becomes inadequate, the exoskeleton gradually adapts to the new task execution so that the increased muscle activity caused by the new desired task can be reduced. The advantage of the proposed method is that it does not require biomechanical or dynamical models. Our proposed learning system uses Dynamical Movement Primitives (DMPs) as a trajectory generator and parameters of DMPs are modulated using Locally Weighted Regression. Then, the learning system is combined with adaptive oscillators that determine the phase and frequency of motion according to measured Electromyography (EMG) signals. We tested the method with real robot experiments where subjects wearing an elbow exoskeleton had to move an object of an unknown mass according to a predefined reference motion. We further evaluated the proposed approach on a whole-arm exoskeleton to show that it is able to adaptively derive assistive torques even for multiple-joint motion. PMID- 26881744 TI - Kinome Profiling of Regulatory T Cells: A Closer Look into a Complex Intracellular Network. AB - Regulatory T cells (Treg) are essential for T cell homeostasis and maintenance of peripheral tolerance. They prevent activation of auto-reactive T effector cells (Teff) in the context of autoimmunity and allergy. Otherwise, Treg also inhibit effective immune responses against tumors. Besides a number of Treg-associated molecules such as Foxp3, CTLA-4 or GARP, known to play critical roles in Treg differentiation, activation and function, the involvement of additional regulatory elements is suggested. Herein, kinase activities seem to play an important role in Treg fine tuning. Nevertheless, our knowledge regarding the complex intracellular signaling pathways controlling phenotype and function of Treg is still limited and based on single kinase cascades so far. To gain a more comprehensive insight into the pathways determining Treg function we performed kinome profiling using a phosphorylation-based kinome array in human Treg at different activation stages compared to Teff. Here we have determined intriguing quantitative differences in both populations. Resting and activated Treg showed an altered pattern of CD28-dependent kinases as well as of those involved in cell cycle progression. Additionally, significant up-regulation of distinct kinases such as EGFR or CK2 in activated Treg but not in Teff not only resemble data we obtained in previous studies in the murine system but also suggest that those specific molecular activation patterns can be used for definition of the activation and functional state of human Treg. Taken together, detailed investigation of kinome profiles opens the possibility to identify novel molecular mechanisms for a better understanding of Treg biology but also for development of effective immunotherapies against unwanted T cell responses in allergy, autoimmunity and cancer. PMID- 26881745 TI - Interocular Difference of Peripheral Refraction in Anisomyopic Eyes of Schoolchildren. AB - PURPOSE: Refraction in the peripheral visual field is believed to play an important role in the development of myopia. The purpose of this study was to investigate the differences in peripheral refraction among anisomyopia, isomyopia, and isoemmetropia for schoolchildren. METHODS: Thirty-eight anisomyopic children were recruited and divided into two groups: (1) both eyes were myopic (anisomyopic group, AM group) and (2) one eye was myopic and the contralateral eye was emmetropic (emmetropic anisomyopic group, EAM group). As controls, 45 isomyopic and isoemmetropic children were also recruited with age and central spherical equivalent (SE) matched to those of the AM and EAM groups. The controls were divided into three groups: (1) intermediate myopia group (SE matched to the more myopic eye of AM group), (2) low myopia group (SE matched to the less myopic eye of AM group and the more myopic eye of EAM group), and (3) emmetropia group (SE matched to the less myopic eye of EAM group). Peripheral refraction at 7 points across the central +/-30 degrees on the horizontal visual field with a 10 degrees interval was measured with an autorefractor. Axial length (AL), corneal curvature (CC), and anterior chamber depth (ACD) were also determined by using the Zeiss IOL-Master. RESULTS: The relative peripheral spherical equivalent [RPR(M)] and relative peripheral spherical value [RPR(S)] of the more myopic eye was shifted more hyperopically than the contralateral eye in both the AM and the EAM groups (both p<0.0001). The RPR(M, S) of the less myopic eyes in the AM and EAM groups showed a relatively flat trend across the visual field and were not significantly different from the emmetropia group. The RPR(M, S) of less myopic eyes in the AM group were shifted less hyperopically than in the isomyopic low myopia group and the more myopic eye of the EAM group [RPR(M), p = 0.007; RPR(S), p = 0.001], although the central SEs of the three groups were not significantly different from each other. However, RPR(M, S) of the more myopic eyes were not different from the corresponding isomyopic groups. There was also no significant difference in the relative peripheral astigmatism [RPR(J0, J45)] between the more and the less myopic eyes in either the AM or the EAM group. CONCLUSION: Refraction of anisomyopia differs between the two eyes not only at the central visual field but also at the off-axis periphery. The relative peripheral refraction of the more myopic eye of anisomyopia was shifted hyperopically, as occurs in isomyopia with similar central subjective SE values. Less myopic eyes were much less hyperopically shifted in relative peripheral refraction than the corresponding isomyopic eyes, but are comparable to emmetropic eyes. This emmetropia-like relative peripheral refraction in less myopic eyes might be a factor responsible for slowing down the progression of myopia. PMID- 26881746 TI - Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet Induced Nonalcoholic Fatty Liver Disease in Mice. AB - Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD. PMID- 26881747 TI - Evaluating Functional Diversity: Missing Trait Data and the Importance of Species Abundance Structure and Data Transformation. AB - Functional diversity (FD) is an important component of biodiversity that quantifies the difference in functional traits between organisms. However, FD studies are often limited by the availability of trait data and FD indices are sensitive to data gaps. The distribution of species abundance and trait data, and its transformation, may further affect the accuracy of indices when data is incomplete. Using an existing approach, we simulated the effects of missing trait data by gradually removing data from a plant, an ant and a bird community dataset (12, 59, and 8 plots containing 62, 297 and 238 species respectively). We ranked plots by FD values calculated from full datasets and then from our increasingly incomplete datasets and compared the ranking between the original and virtually reduced datasets to assess the accuracy of FD indices when used on datasets with increasingly missing data. Finally, we tested the accuracy of FD indices with and without data transformation, and the effect of missing trait data per plot or per the whole pool of species. FD indices became less accurate as the amount of missing data increased, with the loss of accuracy depending on the index. But, where transformation improved the normality of the trait data, FD values from incomplete datasets were more accurate than before transformation. The distribution of data and its transformation are therefore as important as data completeness and can even mitigate the effect of missing data. Since the effect of missing trait values pool-wise or plot-wise depends on the data distribution, the method should be decided case by case. Data distribution and data transformation should be given more careful consideration when designing, analysing and interpreting FD studies, especially where trait data are missing. To this end, we provide the R package "traitor" to facilitate assessments of missing trait data. PMID- 26881748 TI - Pifithrin-MU Attenuates Acute Sickness Response to Lipopolysaccharide in C57BL/6J Mice. AB - Sickness behavior is a coordinated set of behavioral changes that happen as a response to acute infectious pathogens. Its well-known benefit is to reorganize the organism's priorities to cope with infection, but the uncontrolled development of sickness behavior may trigger negative feelings or chronic depressive events. This study aims at investigating the potential effect of pifithrin-MU, an inhibitor of heat shock protein 70 substrate binding activity, on lipopolysaccharide (LPS)-induced sickness response. C57BL/6J mice were submitted to the forced swimming test (FST), tail suspension test (TST), open field test (OFT) and light-dark box test. Food intake and body weight were also evaluated. The serum corticosterone level was measured using an ELISA kit. Treatment of mice with LPS (0.33 mg/kg, i.p.) markedly increased the floating and immobility time in the FST and TST, respectively, and depressed locomotor activity in the OFT. LPS administration prolonged the latency to first transition and reduced the total number of transitions in the light-dark box test. In addition, LPS induced anorexia and increased serum corticosterone levels. Pretreatment with pifithrin-MU (1 or 5 mg/kg) attenuated behavioral changes induced by LPS in the FST, TST, OFT and light-dark box test. Pifithrin-MU also prevented the formation of anorexia as well as the increase in serum corticosterone levels in LPS-treated mice. Our previous studies showed that pifithrin-MU prevents the production of pro-inflammatory factors in both microglia and macrophages. These findings presented here extend the role of pifithrin-MU beyond an anti-inflammatory molecule to a modulator of sickness behavior. PMID- 26881749 TI - Analysing biodiversity and conservation knowledge products to support regional environmental assessments. AB - Two processes for regional environmental assessment are currently underway: the Global Environment Outlook (GEO) and Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Both face constraints of data, time, capacity, and resources. To support these assessments, we disaggregate three global knowledge products according to their regions and subregions. These products are: The IUCN Red List of Threatened Species, Key Biodiversity Areas (specifically Important Bird &Biodiversity Areas [IBAs], and Alliance for Zero Extinction [AZE] sites), and Protected Planet. We present fourteen Data citations: numbers of species occurring and percentages threatened; numbers of endemics and percentages threatened; downscaled Red List Indices for mammals, birds, and amphibians; numbers, mean sizes, and percentage coverages of IBAs and AZE sites; percentage coverage of land and sea by protected areas; and trends in percentages of IBAs and AZE sites wholly covered by protected areas. These data will inform the regional/subregional assessment chapters on the status of biodiversity, drivers of its decline, and institutional responses, and greatly facilitate comparability and consistency between the different regional/subregional assessments. PMID- 26881750 TI - Hydration: The New FIFA World Cup's Challenge for Referee Decision Making? AB - Various continental sporting events have exposed team sports referees to different environmental conditions. Several studies have focused on strategies to prevent athlete performance impairment induced by heat or warm (or both) conditions, but few authors have investigated the effect of heat on referees' performance. In a thermoneutral environment, referees' physical activity induced mild 2.0% dehydration, which was responsible for reductions in physical, psychomotor, and cognitive performances. Therefore, the hydration status of referees should be taken into account to reduce referees' errors and misjudgments in the heat. PMID- 26881751 TI - The Health Care Consequences Of Australian Immigration Policies. PMID- 26881752 TI - Calcitriol Suppression of Parathyroid Hormone Fails to Improve Skeletal Properties in an Animal Model of Chronic Kidney Disease. AB - BACKGROUND: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. METHODS: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). RESULTS: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. CONCLUSIONS: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton. PMID- 26881753 TI - Assessing Discriminative Performance at External Validation of Clinical Prediction Models. AB - INTRODUCTION: External validation studies are essential to study the generalizability of prediction models. Recently a permutation test, focusing on discrimination as quantified by the c-statistic, was proposed to judge whether a prediction model is transportable to a new setting. We aimed to evaluate this test and compare it to previously proposed procedures to judge any changes in c statistic from development to external validation setting. METHODS: We compared the use of the permutation test to the use of benchmark values of the c-statistic following from a previously proposed framework to judge transportability of a prediction model. In a simulation study we developed a prediction model with logistic regression on a development set and validated them in the validation set. We concentrated on two scenarios: 1) the case-mix was more heterogeneous and predictor effects were weaker in the validation set compared to the development set, and 2) the case-mix was less heterogeneous in the validation set and predictor effects were identical in the validation and development set. Furthermore we illustrated the methods in a case study using 15 datasets of patients suffering from traumatic brain injury. RESULTS: The permutation test indicated that the validation and development set were homogenous in scenario 1 (in almost all simulated samples) and heterogeneous in scenario 2 (in 17%-39% of simulated samples). Previously proposed benchmark values of the c-statistic and the standard deviation of the linear predictors correctly pointed at the more heterogeneous case-mix in scenario 1 and the less heterogeneous case-mix in scenario 2. CONCLUSION: The recently proposed permutation test may provide misleading results when externally validating prediction models in the presence of case-mix differences between the development and validation population. To correctly interpret the c-statistic found at external validation it is crucial to disentangle case-mix differences from incorrect regression coefficients. PMID- 26881754 TI - Developmental Eye Movement (DEM) Test Norms for Mandarin Chinese-Speaking Chinese Children. AB - The Developmental Eye Movement (DEM) test is commonly used as a clinical visual verbal ocular motor assessment tool to screen and diagnose reading problems at the onset. No established norm exists for using the DEM test with Mandarin Chinese-speaking Chinese children. This study aims to establish the normative values of the DEM test for the Mandarin Chinese-speaking population in China; it also aims to compare the values with three other published norms for English-, Spanish-, and Cantonese-speaking Chinese children. A random stratified sampling method was used to recruit children from eight kindergartens and eight primary schools in the main urban and suburban areas of Nanjing. A total of 1,425 Mandarin Chinese-speaking children aged 5 to 12 years took the DEM test in Mandarin Chinese. A digital recorder was used to record the process. All of the subjects completed a symptomatology survey, and their DEM scores were determined by a trained tester. The scores were computed using the formula in the DEM manual, except that the "vertical scores" were adjusted by taking the vertical errors into consideration. The results were compared with the three other published norms. In our subjects, a general decrease with age was observed for the four eye movement indexes: vertical score, adjusted horizontal score, ratio, and total error. For both the vertical and adjusted horizontal scores, the Mandarin Chinese-speaking children completed the tests much more quickly than the norms for English- and Spanish-speaking children. However, the same group completed the test slightly more slowly than the norms for Cantonese-speaking children. The differences in the means were significant (P<0.001) in all age groups. For several ages, the scores obtained in this study were significantly different from the reported scores of Cantonese-speaking Chinese children (P<0.005). Compared with English-speaking children, only the vertical score of the 6-year-old group, the vertical-horizontal time ratio of the 8-year-old group and the errors of 9-year-old group had no significant difference (P>0.05); compared with Spanish-speaking children, the scores were statistically significant (P<0.001) for the total error scores of the age groups, except the 6 , 9-, 10-, and 11-year-old age groups (P>0.05). DEM norms may be affected by differences in language, cultural, and educational systems among various ethnicities. The norms of the DEM test are proposed for use with Mandarin Chinese speaking children in Nanjing and will be proposed for children throughout China. PMID- 26881756 TI - Multidimensional Approach to Adequacy of Renal Replacement Therapy in Acute Kidney Injury. AB - Acute kidney injury (AKI) is frequently observed among hospitalized and critical care patients. In the absence of any effective therapies aiming to actively restore kidney function, AKI is usually managed through acute renal replacement therapy (ARRT). 'Optimization' of ARRT may reduce the mortality of patients with AKI. Although several studies have tried to identify the most adequate approach to ARRT in terms of dose, treatment modality and all other important dimensions, the literature has provided controversial results. Nowadays, adequate ARRT still appears difficult to dose, prescribe, deliver and monitor among different critical care patients. The identification of the major elements involved for a multidimensional approach to adequacy of ARRT in patients with AKI should consider the patient, the applied technology and the environment. All these aspects should be carefully evaluated and adequately applied in clinical practice through a patient-oriented approach. Adequacy of ARRT imposes the concomitant consideration of more complex issues, such as the timing, modality and technique of ARRT delivery; anticoagulation and substitution fluid choice; membrane selection; monitor accuracy; the role of fluid overload; and other patient comorbidities. The capacity of clinicians to consider all these aspects through a multidimensional approach, adapting the different dimensions of ARRT to actual patients' needs, might be the fundamental missing element in the pathway toward significant outcome improvements among critically ill patients with AKI. This narrative review provides a systematic approach to the major dimensions of ARRT and their multidimensional rationalization for adequate treatment prescription, monitoring and evaluation. PMID- 26881755 TI - Effect of Serum Cholesterol on Insulin Secretory Capacity: Shimane CoHRE Study. AB - OBJECTIVES: Previous studies indicate that, in addition to the blood glucose level, the lipid level in the blood may affect functions of pancreatic beta cells. In this study, we aimed to examine whether there was a relationship between the serum level of total cholesterol (TC) and the insulin secretory capacity in healthy subjects. SUBJECTS AND METHODS: In participants of health examinations conducted from 2006 to 2010, we analyzed data from a total of 2,499 subjects (1,057 men and 1,442 women) after exclusion of individuals with dyslipidemia, thyroid dysfunction, diabetes, HbA1c>=6.5%, or fasting blood glucose>=126 mg/dL. Homeostasis model assessment for beta cell function (HOMA beta) was utilized as a model representing the pancreatic beta cell function. RESULTS: Although the serum TC level had a positive correlation with HOMA-beta in a univariate correlation analysis, after adjustment by confounding factors in a multiple regression analysis, HOMA-beta had a negative correlation with TC. This was further confirmed in a multiple logistic regression analysis, showing that higher TC was an independent risk factor for decreased insulin secretory capacity (defined as HOMA-beta<=30%) together with higher age, lower BMI, lower TG, male sex and regular alcohol intake. After the participants were stratified by BMI into three groups, the effect of TC on HOMA-beta increased along with the increase in BMI, and it was highly significant in the highest tertile. CONCLUSION: This cross-sectional study indicated that increased serum TC level might be related to the decrease of insulin secretory capacity in aged healthy population and that reduction of TC is more necessary in obese subjects to prevent diabetes. PMID- 26881757 TI - Autofluorescence spectroscopy in the differentiation of laryngeal epithelial lesions - preliminary results. AB - Conclusions Autofluorescence spectroscopy may be a supporting tool for differential diagnosis of changes in laryngeal epithelium. Objectives Early detection and differential diagnosis of proliferative changes in the larynx are still a challenge for laryngologists. The aim of the study was to evaluate the autofluorescence spectroscopy technique to in vitro differential diagnosis of pathological changes in the epithelium of the larynx. Methods Forty-two patients aged 34-79 years were included in the study. The fifty-two tissue specimens, including 10 samples of cancerous lesion, 10 adjacent normal tissue, 10 chronic inflammation, eight cyst, three leukoplakia, four polyp, and seven Reinke's edema, were obtained during laryngological procedures. All tissue samples were independently diagnosed histopathologically. The autofluorescence emission spectra at two excitation wavelengths, 290 nm and 370 nm, were measured for every sample studied. Results The autofluorescence signals of cancerous tissue samples at both excitations exhibited identical emission band shapes of much lower intensities at their maxima as compared to the adjacent healthy tissue samples studied. The autofluorescence spectra intensities of cancerous and normal tissues varied inter-individually. Evident differences in autofluorescence intensities and its band shapes of different pathological laryngeal changes at the 290 nm excitations were demonstrated. PMID- 26881762 TI - RNA conformation: Lightening up invisible states. PMID- 26881763 TI - Translation: Ribosomes make sweeping arrests. PMID- 26881765 TI - Sickness absence and mental health: evidence from a nationally representative longitudinal survey. AB - OBJECTIVES: Previous studies have consistently reported evidence of large significant associations between measures of psychological health and sickness absence. Some of this association, however, may be confounded by relevant covariates that have not been controlled. By using data with repeated observations from the same individuals, this study aimed to quantify the bias due to unobserved characteristics that are time invariant. METHODS: Longitudinal data from the Household, Income, and Labour Dynamics in Australia (HILDA) Survey were used to estimate negative binomial regression models of the number of annual paid sickness absence days. Observations spanning the period 2005-2012, and covering all employed persons aged 15-64 years, were used (56 348 observations from 13 622 individuals). RESULTS: Significant associations between the number of paid sickness absence days taken each year and scores on the mental health subscale of the SF-36 (MHI-5) were found. Inclusion of correlated random effects (which effectively control for unobserved person-specific factors that do not vary over time), however, resulted in a marked decline in the magnitude of this association. For persons with severe depressive symptoms (MHI-5 <=52), the estimated incidence rate ratios were in the range 1.13-1.14 for men and 1.10-1.12 for women. CONCLUSIONS: Poor mental health is a risk factor affecting work attendance, but the magnitude of this effect, at least in a country where the rate of sickness absence is relatively low, is modest. PMID- 26881766 TI - What Do You Mean by Medical Home? PMID- 26881764 TI - Development and application of bond cleavage reactions in bioorthogonal chemistry. AB - Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research. PMID- 26881767 TI - The Changing Drug Culture: Foreword. PMID- 26881768 TI - The Changing Drug Culture: Medical and Recreational Marijuana. AB - The major psychoactive compounds in marijuana (cannabis) are cannabinoids, the most significant of which is delta-9-tetrahydrocannabinol. There are also two synthetic pharmaceutical cannabinoids, nabilone and dronabinol, available by prescription in the United States. The use of marijuana has increased in the United States with passage of medical marijuana laws in many states and legalization of recreational marijuana use in several states. In addition, the potency of marijuana has increased in recent years. Marijuana has been used for a variety of medical purposes, including management of nausea and vomiting, appetite and immunologic stimulation in patients with HIV infection and AIDS, glaucoma, neurologic disorders, and pain relief. Studies on the benefits of marijuana as a treatment for various conditions have been inconsistent, except for those on pain management. Marijuana has adverse effects, and has been associated with driving impairment, psychosis, dependence and withdrawal syndromes, hyperemesis, acute cardiac events, some cancers, and impaired lung function. As with studies on the benefits of marijuana, studies of adverse effects have yielded inconsistent results. Except for impaired driving and the occurrence of dependence and withdrawal syndromes, the adverse effects of marijuana use have not been fully studied. PMID- 26881769 TI - The Changing Drug Culture: Emerging Drugs of Abuse and Legal Highs. AB - In recent years, there has been a large increase in the number of synthetic drugs used recreationally. One class of drugs is synthetic cannabinoids, which are sprayed onto herbal preparations and marketed under names such as K2 and spice. Others include amphetaminelike compounds, such as cathinones (eg, bath salts) and methylenedioxymethamphetamine (MDMA) (eg, ecstasy, Molly). New hallucinogens, such as Bromo-Dragonfly, and hallucinogens that have been used for centuries, such as Salvia divinorum, also are gaining popularity. Because these substances are sold labeled as not for human consumption and because the chemicals in them frequently change, they often are unregulated, and many users consider them legal, although they are not. Their use often goes undetected because testing for them is not included in routine drug screening. Nonetheless, these substances can be associated with significant toxicities, often because their concentrations are unpredictable. Adverse effects of synthetic cannabinoids include psychosis and other effects. Amphetaminelike drugs have stimulant effects and can cause hyponatremia and seizures. The new hallucinogens can cause serious vasoconstriction with ischemia. Clinicians, especially those working with adolescents and young adults (ie, the main users of these drugs), should be aware of these new substances and counsel patients about their adverse effects. PMID- 26881770 TI - The Changing Drug Culture: Use and Misuse of Cognition-Enhancing Drugs. AB - There has been an increase in diagnoses of attention-deficit/hyperactivity disorder (ADHD), with approximately 9% of American children now diagnosed, and a concomitant increase in the use of stimulants (eg, amphetamines, methylphenidate) to manage ADHD. Nonstimulant drugs (eg, atomoxetine, guanfacine, clonidine) also are used, but most patients are treated with stimulants. All of these drugs are effective for management of ADHD, and, overall, use in childhood does not seem to increase the risk of substance abuse later in life. However, widespread use has resulted in prescription stimulants being diverted for nonmedical uses, particularly by high school and college students seeking cognitive enhancement for improved academic performance. Studies of ADHD drugs for improving cognition in patients without ADHD have mixed results, and any improvements appear to be modest and short-term. Other substances also are used for cognitive enhancement. Drugs for Alzheimer disease are being used for mild cognitive impairment, though there is no evidence that they are effective. Creatine may have mild cognition enhancing properties, but study results often are confounded by the addition of exercise, which by itself is thought to improve cognition. There is no evidence that other supplements, such as vitamins and omega-3 fatty acids, improve cognitive function. PMID- 26881771 TI - The Changing Drug Culture: Use and Misuse of Appearance- and Performance Enhancing Drugs. AB - Awareness of the prevalence of the use of appearance- and performance-enhancing drugs (APEDs) is increasing. Users range from professional athletes and bodybuilders to amateurs and adolescents. Anabolic androgenic steroids (AASs) are the most widely used APEDs, typically for purposes of building muscle mass, in forms that include pills, injections, topical preparations, and transdermal systems. AASs are often used in combination with augmenting drugs taken to enhance androgen production and, for men, to decrease estrogen production. These include aromatase inhibitors, clomiphene, selective estrogen receptor modulators, and human chorionic gonadotropin. Other drugs used with the intention of improving athletic performance include human growth hormone, insulinlike growth factor 1, insulin, erythropoietin, stimulants, diuretics, levothyroxine, and gamma-hydroxybutyrate. Use of APEDs is increasing, with up to 5% of male and 2% of female college athletes using AASs and reports of a more than 20% usage rate among teenagers. Although many of these substances can increase muscle mass when combined with high levels of exercise and specific diets, it is not clear that they improve athletic performance. Furthermore, they are associated with a variety of serious adverse effects. AASs, in particular, can cause hepatotoxicity and acute cardiac events. Behavioral and psychiatric symptoms also can occur. PMID- 26881772 TI - Early social isolation increases persistence of alcohol-seeking behavior in alcohol-related contexts. AB - Social conditions during rearing are well known to affect adult alcohol consumption, but few experiments have explored the effects of social conditions on behaviors that are related to alcohol dependence, such as the persistence of alcohol seeking. This study compared the effects of isolation (ISO) and interaction (INT) rearing on the persistence of alcohol-seeking behavior. Rats were trained to lever press for a solution of 10% alcohol diluted in water. They were then exposed to a two-component multiple schedule of reinforcement (baseline). Responses in one component were reinforced by a higher rate of alcohol delivery (rich component, variable interval 15 s) and responses in the other component were reinforced by a lower rate of delivery (lean component, variable interval 45 s). The persistence of lever pressing in the presence of each stimulus was then assessed during extinction. The results from baseline showed that response rates in rats in both groups were higher in the rich component than in the lean component, but ISO rats responded significantly more than INT rats in both components. The persistence of responding during extinction in ISO rats in both components was also higher than that in INT rats. The results show that effects of ISO are not restricted to alcohol consumption, but also affect persistence of alcohol-seeking behavior, which may reflect differences in the value of drug-related stimuli. PMID- 26881773 TI - Caregivers' Attitudes towards HIV Testing and Disclosure of HIV Status to At-Risk Children in Rural Uganda. AB - Caregivers of HIV-positive children were interviewed in the Mbarara and Isingiro districts of Uganda to identify current trends in practices related to HIV testing and the disclosure of HIV status to the child. A total of 28 caregivers of at least one HIV-positive child participated in semi-structured interviews exploring when and why they tested the child for HIV, when the child was informed of their positive status, and what the caregiver did to prepare themselves and the child for status disclosure. For a majority (96%) of respondents, the decision to test the child for HIV was due to existing illness in either the child or a relative. Other common themes identified included the existence of stigma in the caregivers' communities and doubt that the children truly understood what was being explained to them when their status was disclosed. Most (65%) children were informed of their HIV status between the ages of 5 and 9, with the mean age of disclosure occurring at the age of 7. General provision of HIV information typically began at the same age as disclosure, and as many as two thirds (64%) of the caregivers sought advice from an HIV counsellor prior to disclosure. How a caregiver chose to prepare themselves and the child did not affect the caregiver's perception of whether the disclosure experience was beneficial or not. These findings suggest that the HIV disclosure experience in Mbarara and Isingiro districts differs from current guidelines, especially with respect to age of disclosure, how caregivers prepare themselves and the child, and approaching disclosure as an ongoing process. The doubts expressed by caregivers regarding the child's level of HIV understanding following the disclosure experience suggest the children may be insufficiently prepared at the time of the initial disclosure event. The findings also suggest that examining the content of pre-disclosure counselling and HIV education, and how health care professionals are trained to facilitate the disclosure process as important avenues for further research. PMID- 26881774 TI - Clark's Nutcracker Breeding Season Space Use and Foraging Behavior. AB - Considering the entire life history of a species is fundamental to developing effective conservation strategies. Decreasing populations of five-needle white pines may be leading to the decline of Clark's nutcrackers (Nucifraga columbiana). These birds are important seed dispersers for at least ten conifer species in the western U.S., including whitebark pine (Pinus albicaulis), an obligate mutualist of Clark's nutcrackers. For effective conservation of both Clark's nutcrackers and whitebark pine, it is essential to ensure stability of Clark's nutcracker populations. My objectives were to examine Clark's nutcracker breeding season home range size, territoriality, habitat selection, and foraging behavior in the southern Greater Yellowstone Ecosystem, a region where whitebark pine is declining. I radio-tracked Clark's nutcrackers in 2011, a population-wide nonbreeding year following a low whitebark pine cone crop, and 2012, a breeding year following a high cone crop. Results suggest Douglas-fir (Pseudotsuga menziesii) communities are important habitat for Clark's nutcrackers because they selected it for home ranges. In contrast, they did not select whitebark pine habitat. However, Clark's nutcrackers did adjust their use of whitebark pine habitat between years, suggesting that, in some springs, whitebark pine habitat may be used more than previously expected. Newly extracted Douglas-fir seeds were an important food source both years. On the other hand, cached seeds made up a relatively lower proportion of the diet in 2011, suggesting cached seeds are not a reliable spring food source. Land managers focus on restoring whitebark pine habitat with the assumption that Clark's nutcrackers will be available to continue seed dispersal. In the Greater Yellowstone Ecosystem, Clark's nutcracker populations may be more likely to be retained year-round when whitebark pine restoration efforts are located adjacent to Douglas-fir habitat. By extrapolation, whitebark pine restoration efforts in other regions may consider prioritizing restoration of whitebark pine stands near alternative seed sources. PMID- 26881776 TI - Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro. AB - BACKGROUND: In vitro studies suggest that antimicrobial activity of antibiotics meant to treat central nervous system infections such as meningitis or ventriculitis may be altered by cerebrospinal fluid (CSF). This could explain the reason behind the often observed discrepancies between the activity of antibiotics determined in artificial growth media in vitro, and their sometimes reduced clinical efficacy in CSF in vivo. If conducted in CSF, in vitro microbiological investigations might predict the ability of antibiotic drugs to treat CSF infections better than experiments in artificial growth media. In addition, they are less expensive, critical and time consuming than animal studies, and might potentially be appreciated in drug development as a rapid and cost-effective means to gain valuable information on drugs meant to treat infections residing in CSF. SUMMARY: Data from microbiological in vitro experiments performed in CSF were compiled for fosfomycin, rifampicin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin and vancomycin. Where possible, correlations between in vitro data and evidence from in vivo studies were established. KEY MESSAGES: As discussed in the text, no clear correlations between in vitro studies in CSF and clinical outcomes could be identified. Methodological recommendations derived from the collected studies are summarized in order to optimize future research on the topic. PMID- 26881775 TI - CD10-Equipped Melanoma Cells Acquire Highly Potent Tumorigenic Activity: A Plausible Explanation of Their Significance for a Poor Prognosis. AB - CD10 has been widely used in cancer diagnosis. We previously demonstrated that its expression in melanoma increased with tumor progression and predicted poor patient survival. However, the mechanism by which CD10 promotes melanoma progression remains unclear. In order to elucidate the role of CD10 in melanoma, we established CD10-overexpressing A375 melanoma cells and performed DNA microarray and qRT-PCR analyses to identify changes in the gene expression profile. The microarray analysis revealed that up-regulated genes in CD10-A375 were mostly involved in cell proliferation, angiogenesis, and resistance to apoptosis; down-regulated genes mostly belonged to the categories associated with cell adhesion and migration. Accordingly, in functional experiments, CD10-A375 showed significantly greater cell proliferation in vitro and higher tumorigenicity in vivo; CD10 enzymatic inhibitors, thiorphan and phosphoramidon, significantly blocked the tumor growth of CD10-A375 in mice. In migration and invasion assays, CD10-A375 displayed lower migratory and invasive capacity than mock-A375. CD10 augmented melanoma cell resistance to apoptosis mediated by etoposide and gemcitabine. These findings indicate that CD10 may promote tumor progression by regulating the expression profiles of genes related to cell proliferation, angiogenesis, and resistance to apoptosis. PMID- 26881777 TI - Prediction of the intramembranous tissue formation during perisprosthetic healing with uncertainties. Part 1. Effect of the variability of each biochemical factor. AB - A stochastic model is proposed to predict the intramembranous process in periprosthetic healing in the early post-operative period. The methodology was validated by a canine experimental model. In this first part, the effects of each individual uncertain biochemical factor on the bone-implant healing are examined, including the coefficient of osteoid synthesis, the coefficients of haptotactic and chemotactic migration of osteoblastic population and the radius of the drill hole. A multi-phase reactive model solved by an explicit finite difference scheme is combined with the polynomial chaos expansion to solve the stochastic system. In the second part, combined biochemical factors are considered to study a real configuration of clinical acts. PMID- 26881780 TI - Edging closer towards the goal of a dengue vaccine. PMID- 26881778 TI - Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology Genomic Integration Analysis. AB - BACKGROUND: The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess the degree of microenvironmental heterogeneity in breast cancer and correlate this with genomic and clinical parameters. METHODS AND FINDINGS: We developed a quantitative measure of microenvironmental heterogeneity along three spatial dimensions (3-D) in solid tumors, termed the tumor ecosystem diversity index (EDI), using fully automated histology image analysis coupled with statistical measures commonly used in ecology. This measure was compared with disease-specific survival, key mutations, genome-wide copy number, and expression profiling data in a retrospective study of 510 breast cancer patients as a test set and 516 breast cancer patients as an independent validation set. In high grade (grade 3) breast cancers, we uncovered a striking link between high microenvironmental heterogeneity measured by EDI and a poor prognosis that cannot be explained by tumor size, genomics, or any other data types. However, this association was not observed in low-grade (grade 1 and 2) breast cancers. The prognostic value of EDI was superior to known prognostic factors and was enhanced with the addition of TP53 mutation status (multivariate analysis test set, p = 9 * 10-4, hazard ratio = 1.47, 95% CI 1.17-1.84; validation set, p = 0.0011, hazard ratio = 1.78, 95% CI 1.26-2.52). Integration with genome-wide profiling data identified losses of specific genes on 4p14 and 5q13 that were enriched in grade 3 tumors with high microenvironmental diversity that also substratified patients into poor prognostic groups. Limitations of this study include the number of cell types included in the model, that EDI has prognostic value only in grade 3 tumors, and that our spatial heterogeneity measure was dependent on spatial scale and tumor size. CONCLUSIONS: To our knowledge, this is the first study to couple unbiased measures of microenvironmental heterogeneity with genomic alterations to predict breast cancer clinical outcome. We propose a clinically relevant role of microenvironmental heterogeneity for advanced breast tumors, and highlight that ecological statistics can be translated into medical advances for identifying a new type of biomarker and, furthermore, for understanding the synergistic interplay of microenvironmental heterogeneity with genomic alterations in cancer cells. PMID- 26881779 TI - Endovascular Treatment of Acute Ischemic Stroke Due to Tandem Occlusions: Large Multicenter Series and Systematic Review. AB - BACKGROUND: Ischemic strokes due to tandem occlusions (TOs) have poor outcomes if they have been treated with only medical interventions. Recent trials demonstrated the effectiveness of endovascular treatment of acute ischemic stroke due to intracranial occlusions; however, most studies excluded patients with TOs. METHODS: Retrospective review of prospectively collected thrombectomy databases from 3 stroke centers between 2011 and 2015. Consecutive patients with tandem extracranial steno-occlusive carotid disease and intracranial occlusions who underwent emergent thrombectomy were selected. Angiographic and clinical outcomes were analyzed; baseline and procedural variables were included in univariate and multivariate analyses to define the independent predictors of good outcomes (90 day modified Rankin Scale <=2). RESULTS: A total of 100 patients met the study inclusion criteria. The mean age was 64.4 +/- 12.5, baseline National Institutes of Health Stroke Scale (NIHSS) 17.6 +/- 5.0, time from last known well to puncture 7.3 +/- 5.8 h, and Alberta Stroke Program Early CT Score (ASPECTS) 7.5 +/- 1.6. Forty percent received intravenous tissue plasminogen activator. Intracranial occlusion sites included: internal carotid artery thrombus, 31%; middle cerebral artery (MCA)-M1, 53%; MCA-M2, 10%; and anterior cerebral artery, 6%. Good outcome was achieved in 42% and successful reperfusion modified thrombolysis in cerebral infarction (mTICI >=2B) in 88% of the cases, including complete (mTICI 3) reperfusion in 40%. Severe parenchymal hematoma (PH)-2 occurred in 6% of the patients and 90-day mortality was 20%. In the multivariate analysis, younger age (OR 0.93; 95% CI 0.88-0.98; p = 0.004), lower baseline NIHSS (OR 0.84; 95% CI 0.74-0.94; p = 0.003), higher ASPECTS (OR 1.50; 95% CI 1.02-2.19; p = 0.038), and mTICI 3 reperfusion (OR 3.56; 95% CI 1.18-10.76; p = 0.024) were independent predictors of good outcome at 90 days. CONCLUSIONS: Acute endovascular treatment of tandem anterior circulation occlusions yields good outcomes and has similar outcome predictors to isolated intracranial occlusions. Given their comparable clinical behavior, these patients should be included in future trials. PMID- 26881781 TI - Rigid, Inflexible Approach Results in No Recommendation for Autism Screening. PMID- 26881782 TI - Integrative Analysis of the Physical Transport Network into Australia. AB - Effective biosecurity is necessary to protect nations and their citizens from a variety of threats, including emerging infectious diseases, agricultural or environmental pests and pathogens, and illegal wildlife trade. The physical pathways by which these threats are transported internationally, predominantly shipping and air traffic, have undergone significant growth and changes in spatial distributions in recent decades. An understanding of the specific pathways and donor-traffic hotspots created by this integrated physical transport network is vital for the development of effective biosecurity strategies into the future. In this study, we analysed the physical transport network into Australia over the period 1999-2012. Seaborne and air traffic were weighted to calculate a "weighted cumulative impact" score for each source region worldwide, each year. High risk source regions, and those source regions that underwent substantial changes in risk over the study period, were determined. An overall risk ranking was calculated by integrating across all possible weighting combinations. The source regions having greatest overall physical connectedness with Australia were Singapore, which is a global transport hub, and the North Island of New Zealand, a close regional trading partner with Australia. Both those regions with large amounts of traffic across multiple vectors (e.g., Hong Kong), and those with high levels of traffic of only one type (e.g., Bali, Indonesia with respect to passenger flights), were represented among high risk source regions. These data provide a baseline model for the transport of individuals and commodities against which the effectiveness of biosecurity controls may be assessed, and are a valuable tool in the development of future biosecurity policy. PMID- 26881783 TI - Sonographic and Clinical Features of Papillary Thyroid Microcarcinoma Less than or Equal to Five Millimeters: A Retrospective Study. AB - OBJECTIVE: To retrospectively compare the sonographic and clinical features of papillary thyroid microcarcinoma (PTMC) <=5 mm and PTMC >5 mm to improve the diagnostic value of ultrasonography. METHODS: A total of 367 cases of PTMC between January 2013 and December 2014 was included in this study. The patients were classified into group A (<=5 mm, n = 181) or group B (>5 mm, n = 186), and the sonographic and clinical features were reviewed and compared between the two groups. RESULTS: There was no significant difference in the shape, ratio of length/width, boundary, peripheral halo ring, echogenicity, cystic change and accompanying Hashimoto's thyroiditis between these two groups. However, the calcification (61.3% vs. 72.6%) and hypervascularity (13.8% vs. 24.7%) were more frequent in group B (p = 0.026 and 0.008, respectively). The patients were younger, and more patients were aged less than 45 years (41.4% vs. 57.0%) in group B. Capsular invasion (7.2% vs. 34.4%), multifocality (21.5% vs. 48.9%), bilaterality (17.1% vs. 39.8%), central lymph node metastasis (13.8% vs. 38.2%) and lateral lymph node metastasis (1.1% vs. 5.4%) were more frequent in group B. No clinical or sonographic feature was related to cervical lymph node metastasis in group A, while less than 45 years in age (p = 0.010), male gender (p = 0.040), capsular invasion (p<0.001), multifocality (p = 0.016) and calcification (p = 0.042) were related to cervical lymph node metastasis in group B. CONCLUSIONS: The sonographic features of PTMC <=5 mm were similar to those of PTMC >5 mm, including an irregular shape, a length/width ratio of >=1, an unclear boundary, no peripheral halo ring, hypoechogenicity, no cystic change, calcification, no hypervascularity and no accompanying Hashimoto's thyroiditis. The clinical features of PTMC <=5 mm were less aggressive than those of PTMC >5 mm. PMID- 26881784 TI - Influence of Landscape Diversity and Composition on the Parasitism of Cotton Bollworm Eggs in Maize. AB - We deployed >50,000 Helicoverpa armigera eggs in maize fields to assess the rate of parasitism by Trichogramma chilonis across 33 sites during a three-year span (2012-2014) in northern China. Subsequently, we used a partial least squares (PLS) regression approach to assess the relationship of landscape diversity with composition and parasitism potential. The parasitism rate of H. armigera eggs by T. chilonis ranged from 0-25.8%, with a mean value of 5.6%. Landscape diversity greatly enhanced parasitism at all four different spatial scales (0.5, 1.0, 1.5 and 2.0 km radius). Both the proportion of arable area and the total planting area of two major crops (cotton and maize) had a negative correlation to the parasitism rate at each scale, whereas parasitism was positively correlated to the proportion of host crops of H. armigera other than cotton and maize at the 0.5 to 2.0 km radius scales as well as to that of non-crop habitat at the 0.5 and 1.0 km radius scales. The study indicated that maintaining landscape diversity provided an important biocontrol service by limiting H. armigera through the egg parasitoid T. chilonis, whereas rapid agricultural intensification would greatly reduce the presence and parasitism of T. chilonis in China. PMID- 26881785 TI - Remote heart function monitoring: role of the CardioMEMS HF System. AB - Heart failure is a pandemic condition that is challenging cardiology today. The primary economical and social burden of this syndrome is hospitalization rate whose costs represent the highest ones within the entire healthcare management. Remote monitoring of physiological data, obtained through self-reporting via telephone calls or, automatically, using external devices is a potential novel approach to implement management of patients with heart failure and reduce hospitalization rates. Relatively large but, sometimes, contradicting information exists about the efficacy of remote monitoring via different noninvasive approaches to reduce the economical and social burden of heart failure management. This leaves still partly unaddressed this critical issue and generates the need for new approaches. In this context, the CardioMEMS device that can chronically monitor pulmonary pressures from a small microchip inserted transvenously in the pulmonary artery seems to represent an innovative tool to challenge hospitalization rates. Consecutive analyses from the CHAMPION study had indeed documented the efficacy of the CardioMEMS in the remote monitoring of the pulmonary circulation status of patients with heart failure and in providing adequate information to optimally manage such patients with the final result of a significant hospitalization rate reduction. The striking information here is that this appears to be true in patients with preserved left ventricular ejection fraction also. Overall, the reports from the CHAMPION study encourage the use of CardioMEMS but larger populations are needed to definitively prove its value. PMID- 26881787 TI - Low-Dose IL-2 In Vivo Treg Expansion Limits Rejection in Corneal Grafting. PMID- 26881786 TI - Immigration transition and sleep-related symptoms experienced during menopausal transition. AB - The transition due to immigration from one country to another country (referred to as immigration transition henceforth) is inherently stressful, placing an additional dimension of stress to midlife women in the menopausal transition. However, few studies have examined the association of immigration to sleep related symptoms experienced by midlife women in the menopausal transition. The authors' purpose for this study was to explore the associations of immigration to sleep-related symptoms among four major racial/ethnic groups of 1,054 midlife women in the United States. This was a secondary analysis of data from two national surveys that were collected from 2005 to 2013. The instruments included questions on background characteristics, health and menopausal status, immigration transition, and the Sleep Index for Midlife Women. The data were analyzed using t-tests, chi-square tests, correlation analyses, and hierarchical multiple regression analyses. Immigrants reported fewer total numbers of and lower total severity scores of sleep-related symptoms than non-immigrants (p < .01). Yet, when background characteristics and health and menopausal status were controlled, self-reported racial/ethnic identity was the only significant factor associated with sleep-related symptoms (DeltaR2 = 0.02, p < .01). Health-care providers need to consider self-reported racial/ethnic identity as a factor significantly related to sleep-related symptoms during the menopausal transition. PMID- 26881789 TI - Self-Determination Theory and Computer-Mediated Support: Modeling Effects on Breast Cancer Patient's Quality-of-Life. AB - A breast cancer diagnosis typically results in dramatic and negative effects on an individual's quality of life. Web-based interactive support systems such as the Comprehensive Health Enhancement Support System (CHESS) offer one avenue for mitigating these negative effects. While evidence supports the efficacy of such systems, evaluations typically fail to provide a true test of the theorized model of effects, treating self-determination theory's constructs of competence, relatedness, and autonomy as outcomes rather than mediators. Using path analysis, this study tests the nature of the proposed mediated relationship between system engagement and quality-of-life indicators utilizing data collected from women (N = 90) who participated in the treatment condition of a CHESS randomized controlled trial. Findings support a latent model, indicating that system effects are mediated through an intertwined measure of autonomy, competence, and relatedness. PMID- 26881788 TI - In Vivo Expansion of Regulatory T Cells by Low-Dose Interleukin-2 Treatment Increases Allograft Survival in Corneal Transplantation. AB - BACKGROUND: Corneal allograft survival dramatically decreases in hosts with inflamed or vascularized recipient beds. We have previously shown that in rejected corneal allografts regulatory T cells (Treg) demonstrate diminished Foxp3 expression and immunoregulatory function. Treatment with low doses of IL-2 selectively expands Treg and has been proposed for the treatment of autoimmune diseases. In this study, we investigated the effect of low-dose IL-2 administration on Treg function and corneal allograft survival. METHODS: Allogeneic corneal transplantation was performed on inflamed host beds. Low-dose systemic IL-2 was administered starting 3 days before grafting until 6 weeks after transplantation. Frequencies of Treg and their immunosuppressive function and antigen specificity were assessed using flow cytometry, in vitro proliferation assays, and adoptive transfer experiments. Frequencies of effector T cells (Teff) and graft infiltrating immune cells were measured at 2 weeks posttransplantation. Long-term allograft survival was evaluated for up to 9 weeks using Kaplan-Meier survival analysis. RESULTS: Treatment with low-dose IL-2 significantly increased frequencies of CD4CD25Foxp3 Treg and their immunosuppressive function. It also suppressed alloimmune response as shown by the decreased CD4 IFNgamma T cell frequencies and graft infiltration of CD45 and CD4 cells. Clinical evaluation of the grafts showed significant improvement in long-term corneal allograft survival in the IL-2 treated group compared with controls. CONCLUSIONS: Our study is the first to report that treatment with low dose IL-2 increases survival of corneal allografts. We propose that IL-2-mediated Treg expansion can be an effective tool to prevent alloimmunity and to improve long-term allograft survival in transplantation. PMID- 26881791 TI - [Not Available]. PMID- 26881792 TI - [New indicator needed for follow up of osteoporosis patients]. PMID- 26881793 TI - ["Active health management" can provide support for vulnerable patients. New model for the prevention of unplanned healthcare]. AB - A small group of frequent emergency department visitors account for a disproportionally large fraction of health care consumption, including unplanned hospitalizations and overall healthcare costs. In response, case and disease management programs aimed at reducing health care consumption in this group have been tested, however results vary widely. In this study, we aimed to investigate if a telephone-based, nurse led case management intervention can reduce health care consumption for frequent emergency department visitors in a large-scale set up. A total of 12,181 frequent emergency department users in three counties in Sweden were randomized either using Zelen's design or a traditional randomized design to receive a nurse led case management intervention or no intervention. Patients were followed for health care consumption for up to 2 years. The results of the study with traditional design showed an overall 12% (95% confidence interval [CI], 4-19%) decreased rate of hospitalization, which was mostly driven by effects among patients included in the last year. Similar results were achieved in the Zelen studies, with significant reduction of hospitalization, again in the last year, but mixed results in the early development of the project. Our study provides evidence that a carefully designed telephone-based intervention with accurate and systematic patient selection and appropriate staff training in a centralized set-up can lead to significant decreases in health care consumption and costs. However, we also demonstrate that the effects are sensitive to the delivery model chosen. PMID- 26881794 TI - [Not Available]. AB - The evidence for the beneficial health effects of moderate drinking is weaker than commonly perceived. No randomised controlled trials have been done. Observational studies suffer from unavoidable methodological limitations, chiefly from confounding and misclassification. Clinical advice to patients as well as public health recommendations should discourage initiation of alcohol consumption, as well as recommend the reduction of excessive drinking. The absence of health benefits strengthens the the arguments for effective population level policies, e.g. raising alcohol prices and restricting the physical availability of alcohol. PMID- 26881790 TI - Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. AB - Rhabdomyolysis is common in very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) and other metabolic myopathies, but its pathogenic basis is poorly understood. Here, we show that prolonged bicycling exercise against a standardized moderate workload in VLCADD patients is associated with threefold bigger changes in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations in quadriceps muscle and twofold lower changes in plasma acetyl carnitine levels than in healthy subjects. This result is consistent with the hypothesis that muscle ATP homeostasis during exercise is compromised in VLCADD. However, the measured rates of PCr and Pi recovery post-exercise showed that the mitochondrial capacity for ATP synthesis in VLCADD muscle was normal. Mathematical modeling of oxidative ATP metabolism in muscle composed of three different fiber types indicated that the observed altered energy balance during submaximal exercise in VLCADD patients may be explained by a slow-to-fast shift in quadriceps fiber-type composition corresponding to 30% of the slow-twitch fiber-type pool in healthy quadriceps muscle. This study demonstrates for the first time that quadriceps energy balance during exercise in VLCADD patients is altered but not because of failing mitochondrial function. Our findings provide new clues to understanding the risk of rhabdomyolysis following exercise in human VLCADD. PMID- 26881795 TI - [Not Available]. PMID- 26881796 TI - [Not Available]. PMID- 26881797 TI - [Not Available]. PMID- 26881798 TI - [Not Available]. PMID- 26881799 TI - [Not Available]. PMID- 26881800 TI - [Analyze, listen, correct, apologize and learn. How an organization becomes safer - and better]. PMID- 26881801 TI - [Not Available]. PMID- 26881802 TI - Acute Kidney Injury Epidemiology: From Recognition to Intervention. AB - Acute kidney injury (AKI) is very common among hospitalized patients, and the incidence of AKI has increased over the past few decades. This increase might be due to an aging population and increased comorbidities. Other factors that may explain this are the more sensitive diagnostic criteria and better recognition. AKI is associated with increased mortality and increased risks of chronic kidney disease and end-stage renal disease. The best ways to lower the chances of having kidney damage are to prevent, recognize and treat AKI as early as possible. The incidence of AKI in China is significantly lower than in developed countries. Inadequate early diagnosis and management remain the major challenges for Chinese nephrologists. PMID- 26881803 TI - The Impact of Competitive Trait Anxiety on Collegiate Powerlifting Performance. AB - Judge, LW, Urbina, LJ, Hoover, DL, Craig, BW, Judge, LM, Leitzelar, BM, Pearson, DR, Holtzclaw, KA, and Bellar, DM. The impact of competitive trait anxiety on collegiate powerlifting performance. J Strength Cond Res 30(9): 2399-2405, 2016 The purpose of this study was to determine the relationship between competitive trait anxiety measures and powerlifting (PL) performance. Thirty-six collegiate powerlifters on club teams from 3 universities were recruited during a competition (men = 26, women = 10; age = 19.9 +/- 1.5 years; height = 172.5 +/- 8.6 cm; weight = 81.4 +/- 21.0 kg). The athletes were distributed across weight classes for collegiate PL (47.6 kg: 1; 51.7 kg: 1; 54.9 kg: 1; 59.8 kg: 3; 67.1 kg: 2; 74.8 kg: 7; 82.1 kg: 4; 89.8 kg: 9; 99.8 kg: 5; super heavyweight: 3). A survey containing questions about PL performance history and the 15-item Sport Competition Anxiety Test (SCAT) were administered to the participants before competing. The SCAT total was negatively correlated (r = -0.397; p = 0.02) to the athletes' percentage of best total achieved in the competition (actual performance total/best comp total * 100). Of the individual lifts, the SCAT score was negatively correlated to the personal best for bench press (r = -0.368; p = 0.03) and deadlift (r = -0.317, p = 0.05), but did not significantly correlate for squat (r = -0.182, p = 0.27). These results indicate a negative correlation between the SCAT score and athletes' personal best totals in PL. Increased SCAT scores were associated with decreased personal best PL totals. The results suggest that competitive trait anxiety may have negatively impacted performance and that some PL athletes may benefit from interventions aimed at decreasing anxiety before and during performance. PMID- 26881805 TI - Simultaneous inference of a binary composite endpoint and its components. AB - Binary composite endpoints offer some advantages as a way to succinctly combine evidence from a number of related binary endpoints recorded in the same clinical trial into a single outcome. However, as some concerns about the clinical relevance as well as the interpretation of such composite endpoints have been raised, it is recommended to evaluate the composite endpoint jointly with the involved components. We propose an approach for carrying out simultaneous inference based on separate model fits for each endpoint, yet controlling the familywise type I error rate asymptotically. The key idea is to stack parameter estimates from the different fits and derive their joint asymptotic distribution. Simulations show that the proposed approach comes closer to nominal levels and has comparable or higher power as compared to existing approaches, even for moderate sample sizes (around 100-200 observations). The method is compared to the gatekeeping approach and results are provided in the Supplementary Material. In two data examples we show how the procedure may be adapted to handle local significance levels specified through a priori given weights. PMID- 26881804 TI - Characterization of a Decapentapletic Gene (AccDpp) from Apis cerana cerana and Its Possible Involvement in Development and Response to Oxidative Stress. AB - To tolerate many acute and chronic oxidative stress-producing agents that exist in the environment, organisms have evolved many classes of signal transduction pathways, including the transforming growth factor beta (TGFbeta) signal pathway. Decapentapletic gene (Dpp) belongs to the TGFbeta superfamily, and studies on Dpp have mainly focused on its role in the regulation of development. No study has investigated the response of Dpp to oxidative pressure in any organism, including Apis cerana cerana (A. cerana cerana). In this study, we identified a Dpp gene from A. cerana cerana named AccDpp. The 5? flanking region of AccDpp had many transcription factor binding sites that relevant to development and stress response. AccDpp was expressed at all stages of A. cerana cerana, with its highest expression in 15-day worker bees. The mRNA level of AccDpp was higher in the poison gland and midgut than other tissues. Furthermore, the transcription of AccDpp could be repressed by 4 degrees C and UV, but induced by other treatments, according to our qRT-PCR analysis. It is worth noting that the expression level of AccDpp protein was increased after a certain time when A. cerana cerana was subjected to all simulative oxidative stresses, a finding that was not completely consistent with the result from qRT-PCR. It is interesting that recombinant AccDpp restrained the growth of Escherichia coli, a function that might account for the role of the antimicrobial peptides of AccDpp. In conclusion, these results provide evidence that AccDpp might be implicated in the regulation of development and the response of oxidative pressure. The findings may lay a theoretical foundation for further genetic studies of Dpp. PMID- 26881806 TI - Age of Sexual Debut and Cannabis Use in the United States. AB - BACKGROUND: Understanding the interrelationships between risky health behaviors is critical for health promotion efforts. Conceptual frameworks for understanding substance misuse (e.g. stepping-stone models) have not yet widely incorporated other risky behaviors, including those related to sexual health. OBJECTIVES: The goals of this study were to assess the relationship between early sexual debut and cannabis use, examine the role of licit substance use in this association, and evaluate differences by gender and race/ethnicity. METHODS: Data came from the National Comorbidity Survey-Replication (NCS-R). Primary analysis was restricted to respondents who reported sexual debut at >=12 years (n = 5,036). Age at sexual debut was categorized as early (<18 years), average (18 years) and late (>18 years). Logistic regression was used to assess the relationship between age at sexual debut and cannabis use. Interaction terms were used to evaluate effect modification by gender and race/ethnicity. RESULTS: Later age of sexual debut was associated with lower odds of cannabis use relative to the average age of debut (AOR = 0.50, 95% CI = 0.37-0.66). For every year that respondents delayed their sexual debut, the relative odds of lifetime cannabis use declined by 17%. After accounting for alcohol and tobacco use the association between early sexual debut and cannabis was attenuated (AOR = 0.90, 95% CI = 0.68-1.20), while later age of debut remained protective (AOR = 0.57, 95% CI = 0.42-0.78). Results were generally consistent across race/ethnicity and gender. CONCLUSIONS: Multifactorial intervention strategies targeting both sexual health and substance use may be warranted. PMID- 26881807 TI - Conceptualization and Development of the Leg Activity Measure (LegA) for Patient and Carer Reported Assessment of Activity in the Paretic Leg. AB - BACKGROUND AND PURPOSE: The purpose of the paper is to develop a patient-reported outcome measure of active and passive function in the paretic lower limb with associated spasticity. METHODS: Potential items for inclusion were identified through (1) systematic review and analysis of existing measures and (2) analysis of the primary goals for treatment in a spasticity service. Ethical approval for re-evaluation of routinely collected data was received. Item reduction was achieved through consultation with a purposively selected group of experienced physiotherapists and occupational therapists (n = 16) in a two-round Delphi process. This was followed by a review of Delphi consultation findings by the Project Advisory Group consisting of patients and carers. RESULTS: Development of the leg activity measure (LegA) included two rounds of Delphi consultation, which resulted in a high degree of agreement (80% in round 2) between respondents in rounds 1 and 2. From an initial shortlist of 126 items, 29 items were initially identified for inclusion in LegA and subsequently refined to a 24-item (two sub scales) tool consisting of nine passive function and 15 active function items. DISCUSSION: The Delphi consultation with clinicians experienced in this area of practice ensured content validity and appropriate reduction of items. In common with previous work in the upper limb, a 5-point ordinal scaling structure was chosen, with ratings based on activity over the preceding 7 days. The LegA is designed to measure passive and active function following focal interventions associated with spasticity in the lower limb. Content and face validity have initially been addressed within the development process. The next phase of development will involve formal evaluation of psychometric properties. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26881808 TI - Physiological and Transcriptome Responses to Combinations of Elevated CO2 and Magnesium in Arabidopsis thaliana. AB - The unprecedented rise in atmospheric CO2 concentration and injudicious fertilization or heterogeneous distribution of Mg in the soil warrant further research to understand the synergistic and holistic mechanisms involved in the plant growth regulation. This study investigated the influence of elevated CO2 (800 MUL L(-1)) on physiological and transcriptomic profiles in Arabidopsis cultured in hydroponic media treated with 1 MUM (low), 1000 MUM (normal) and 10,000 MUM (high) Mg2+. Following 7-d treatment, elevated CO2 increased the shoot growth and chlorophyll content under both low and normal Mg supply, whereas root growth was improved exclusively under normal Mg nutrition. Notably, the effect of elevated CO2 on mineral homeostasis in both shoots and roots was less than that of Mg supply. Irrespective of CO2 treatment, high Mg increased number of young leaf but decreased root growth and absorption of P, K, Ca, Fe and Mn whereas low Mg increased the concentration of P, K, Ca and Fe in leaves. Transcriptomics results showed that elevated CO2 decreased the expression of genes related to cell redox homeostasis, cadmium response, and lipid localization, but enhanced signal transduction, protein phosphorylation, NBS-LRR disease resistance proteins and subsequently programmed cell death in low-Mg shoots. By comparison, elevated CO2 enhanced the response of lipid localization (mainly LTP transfer protein/protease inhibitor), endomembrane system, heme binding and cell wall modification in high-Mg roots. Some of these transcriptomic results are substantially in accordance with our physiological and/or biochemical analysis. The present findings broaden our current understanding on the interactive effect of elevated CO2 and Mg levels in the Arabidopsis, which may help to design the novel metabolic engineering strategies to cope with Mg deficiency/excess in crops under elevated CO2. PMID- 26881809 TI - Physiological and molecular mechanisms mediating xylem Na+ loading in barley in the context of salinity stress tolerance. AB - Time-dependent kinetics of xylem Na+ loading was investigated using a large number of barley genotypes contrasting in their salinity tolerance. Salt sensitive varieties were less efficient in controlling xylem Na+ loading and showed a gradual increase in the xylem Na+ content over the time. To understand underlying ionic and molecular mechanisms, net fluxes of Ca2+ , K+ and Na+ were measured from the xylem parenchyma tissue in response to H2 O2 and ABA; both of them associated with salinity stress signalling. Our results indicate that NADPH oxidase-mediated apoplastic H2 O2 production acts upstream of the xylem Na+ loading and is causally related to ROS-inducible Ca2+ uptake systems in the root stelar tissue. It was also found that ABA regulates (directly or indirectly) the process of Na+ retrieval from the xylem and the significant reduction of Na+ and K+ fluxes induced by bumetanide are indicative of a major role of chloride cation co-transporter (CCC) on xylem ion loading. Transcript levels of HvHKT1;5_like and HvSOS1_like genes in the root stele were observed to decrease after salt stress, while there was an increase in HvSKOR_like gene, indicating that these ion transporters are involved in primary Na+ /K+ movement into/out of xylem. PMID- 26881812 TI - Comparison of the HEART and TIMI Risk Scores for Suspected Acute Coronary Syndrome in the Emergency Department. AB - OBJECTIVES: The emergency department evaluation for suspected acute coronary syndrome (ACS) is common, costly, and challenging. Risk scores may help standardize clinical care and screening for research studies. The Thrombolysis in Myocardial Infarction (TIMI) and HEART are two commonly cited risk scores. We tested the null hypothesis that the TIMI and HEART risk scores have equivalent test characteristics. METHODS: We analyzed data from the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS) from 9 EDs on patients with suspected ACS, 1999-2001. We excluded patients with an emergency department diagnosis consistent with ACS, or without sufficient data to calculate TIMI and HEART scores. The primary outcome was 30-day major adverse cardiovascular events, including all-cause death, acute myocardial infarction, and urgent revascularization. We describe test characteristics of the TIMI and HEART risk scores. RESULTS: The study cohort included 8255 patients with 508 (6.2%) 30-day major adverse cardiovascular events. Receiver operating curve and reclassification analyses favored HEART [c statistic: 0.753, 95% confidence interval (CI): 0.733-0.773; continuous net reclassification improvement: 0.608, 95% CI: 0.527-0.689] over TIMI (c statistic: 0.678, 95% CI: 0.655-0.702). A HEART score 0-3 [negative predictive value (NPV) 0.982, 95% CI: 0.978-0.986; positive predictive value (PPV) 0.103, 95% CI: 0.094-0.113; likelihood ratio (LR) positive 1.76; LR negative 0.28] demonstrates similar or superior NPV/PPV/LR compared with TIMI = 0 (NPV 0.978, 95% CI: 0.971-0.983; PPV 0.077, 95% CI: 0.071-0.084; LR positive 1.28; LR negative 0.35) and TIMI = 0-1 (NPV 0.963, 95% CI: 0.958-0.968; PPV 0.102, 95% CI: 0.092-0.113; LR positive 1.73; LR negative 0.58). CONCLUSIONS: The HEART score has better discrimination than TIMI and outperforms TIMI within previously published "low-risk" categories. PMID- 26881813 TI - Discriminative Power of the HEART Score for Obstructive Coronary Artery Disease in Acute Chest Pain Patients Referred for CCTA. AB - OBJECTIVE: To investigate the ability of the HEART score to predict the presence of obstructive coronary artery disease (CAD) determined by coronary computed tomography angiography (CCTA) and its ability to predict the occurrence of major adverse cardiac events (MACE) in patients referred for CCTA after emergency department (ED) presentation. METHODS: From December 2011 to August 2014, 710 ED patients with chest pain who underwent CCTA within 30 days were included. The HEART score was retrospectively calculated and patients were followed for MACE, comprised of death, myocardial infarction, and revascularization. Association of CAD at CCTA in the different categories of the HEART score was analyzed using chi test. The performance of the HEART score in discriminating between those with and without obstructive CAD was evaluated by receiver operating characteristics. Kaplan-Meier analysis was used to assess MACE-free survival stratified by HEART score categories. RESULTS: During median follow-up of 826 days (interquartile range: 563-1056), MACE occurred in 46 (6.5%) patients; 3 (0.4%) myocardial infarction, 8 (1.1%) death, and 36 (5.1%) revascularizations. A low HEART score was a significant predictor for MACE-free survival (P = 0.010). CCTA revealed obstructive CAD in 11.7% of patients, with no significant difference between patients with a low and intermediate/high HEART score, respectively 10.7% and 13.2% (P = 0.29). The ability of the HEART score to identify obstructive CAD was poor with an AUC of the receiver operating characteristics curve of 0.53. CONCLUSION: The HEART score does not adequately identify patients with obstructive CAD at CCTA. It does however predict occurrence of MACE in medium term follow-up. Excluding patients from additional testing based solely on a low HEART score may lead to suboptimal patient management. CCTA had important implications on patient management and may be a more appropriate tool to further stratify risk in ED chest pain patients. PMID- 26881814 TI - Cardiac Computed Tomography in Certified German Chest Pain Units. AB - OBJECTIVE: The German Cardiac Society runs a nation-wide certification campaign for specialized chest pain units (CPUs). So far, cardiac computed tomography (CT) is not an integral part of such certification. The aim of our study was to analyze whether or not cardiac CT is nevertheless routinely used for further stratification in low-risk patients. METHODS: For the time interval from January 2010 to April 2011, data were retrieved from the mandatory German CPU registry. Patients with and without cardiac CT during CPU index stay were compared. RESULTS: Out of 5800 patients, 314 patients (5.4%) underwent cardiac CT during the index CPU stay. Unstable angina pectoris was the most common diagnosis when performing cardiac CT [34.4% vs. 17.7%; odds ratio (OR), 2.44; confidence interval (CI), 1.91-3.11; P < 0.001). Patients undergoing cardiac CT received significantly less often coronary angiography (31.8% vs. 54.8%; OR, 0.39; CI, 0.30-0.49; P < 0.001) or coronary revascularization (15.6% vs. 36.5%; OR, 0.32; CI, 0.23-0.46; P < 0.001). The use of cardiac CT did not prolong the length of stay in the CPU (20:48 vs. 20:25 h, P = 0.21). CONCLUSIONS: Cardiac CT is underrepresented within the diagnostic work up in certified CPUs in Germany, although its use reduces unnecessary invasive diagnostics. The use of cardiac CT should be reconsidered during the next update of the CPU certification criteria. PMID- 26881815 TI - Characteristics of ST Elevation Myocardial Infarction Patients Who Do Not Undergo Percutaneous Coronary Intervention After Prehospital Cardiac Catheterization Laboratory Activation. AB - OBJECTIVES: To assess the clinical and electrocardiographic characteristics of patients diagnosed with ST elevation myocardial infarction (STEMI) that are associated with an increased likelihood of not undergoing percutaneous coronary intervention (PCI) after prehospital Cardiac Catheterization Laboratory activation in a regional STEMI system. METHODS: We performed a retrospective analysis of prehospital Cardiac Catheterization Laboratory activations in Mecklenburg County, North Carolina, between May 2008 and March 2011. Data were extracted from the prehospital patient record, the prehospital electrocardiogram, and the regional STEMI database. The independent variables of interest included objective patient characteristics as well as documented cardiac history and risk factors. Analysis was performed using descriptive statistics and logistic regression. RESULTS: Two hundred thirty-one prehospital activations were included in the analysis. Five independent variables were found to be associated with an increased likelihood of not undergoing PCI: increasing age, bundle branch block, elevated heart rate, left ventricular hypertrophy, and non-white race. The variables with the most significance were any type of bundle branch block [adjusted odds ratios (AOR), 5.66; 95% confidence interval (CI), 1.91-16.76], left ventricular hypertrophy (AOR, 4.63; 95% CI, 2.03-10.53), and non-white race (AOR, 3.53; 95% CI, 1.76-7.08). Conversely, the only variable associated with a higher likelihood of undergoing PCI was the presence of arm pain (AOR, 2.94; 95% CI, 1.36-6.25). CONCLUSIONS: Several of the above variables are expected electrocardiogram mimics; however, the decreased rate of PCI in non-white patients highlights an area for investigation and process improvement. This may guide the development of prehospital STEMI protocols, although avoiding false positive and inappropriate activations. PMID- 26881816 TI - The Comparison of Physician to Computer Interpreted Electrocardiograms on ST elevation Myocardial Infarction Door-to-balloon Times. AB - OBJECTIVE: The purpose of the project was to study the impact that immediate physician electrocardiogram (ECG) interpretation would have on door-to-balloon times in ST-elevation myocardial infarction (STEMI) as compared with computer interpreted ECGs. METHODS: This was a retrospective cohort study of 340 consecutive patients from September 2003 to December 2009 with STEMI who underwent emergent cardiac catheterization and percutaneous coronary intervention. Patients were stratified into 2 groups based on the computer interpreted ECG interpretation: those with acute myocardial infarction identified by the computer interpretation and those not identified as acute myocardial infarction. Patients (n = 173) from September 2003 to June 2006 had their initial ECG reviewed by the triage nurse, while patients from July 2006 to December 2009 (n = 167) had their ECG reviewed by the emergency department physician within 10 minutes. Times for catheterization laboratory activation and percutaneous coronary intervention were recorded in all patients. RESULTS: Of the 340 patients with confirmed STEMI, 102 (30%) patients were not identified by computer interpretation. Comparing the prior protocol of computer ECG to physician interpretation, the latter resulted in significant improvements in median catheterization laboratory activation time {19 minutes [interquartile range (IQR): 10-37] vs. 16 minutes [IQR: 8-29]; P < 0.029} and in median door-to balloon time [113 minutes (IQR: 86-143) vs. 85 minutes (IQR: 62-106); P < 0.001]. CONCLUSION: The computer-interpreted ECG failed to identify a significant number of patients with STEMI. The immediate review of ECGs by an emergency physician led to faster activation of the catheterization laboratory, and door-to-balloon times in patients with STEMI. PMID- 26881817 TI - There's Another Observation Unit?: A Case Series Survey of Second Level Observation Units. AB - OBJECTIVES: Observation units are dedicated areas in the hospital to deliver care to patients in observation status-those too risky to be immediately discharged following an emergency department evaluation but also clearly not in need of an inpatient admission. Observation units have been commonplace for several decades but in recent years some hospitals have begun to operate an additional observation unit with a distinct care delivery model and patient population. METHODS: We conducted a survey between June 2014 and December 2014 to determine the prevalence and key operational characteristics of second level observation units in the US. We accessed the list serve of a large specialty organization to reach leaders likely to be directly operating or aware of the presence of a second level unit in their hospital. RESULTS: We received 28 responses (response rate of approximately 10%). We found 8 second level OUs, with respondents able to provide detailed data for 6 of them. All were established within the past 5 years. CONCLUSIONS: Second level observation units are still relatively uncommon but are emerging as an extension of hospital-based observation services as an additional resource to cohort observation patients into a dedicated unit. These units share some similarities with traditional OUs, such as the nursing ratio of approximately 4:1 and the preponderance of chest pain pathways; however, they also differ in important ways around key metrics, such as length of stay, attending staffing coverage, and rate of subsequent inpatient admission. Additional study is needed both to fully characterize these units and their potential benefits. PMID- 26881818 TI - First Update of the Criteria for Certification of Chest Pain Units in Germany: Facelift or New Model? AB - OBJECTIVE: In an effort to provide a systematic and specific standard-of-care for patients with acute chest pain, the German Cardiac Society introduced criteria for certification of specialized chest pain units (CPUs) in 2008, which have been replaced by a recent update published in 2015. METHODS: We reviewed the development of CPU establishment in Germany during the past 7 years and compared and commented the current update of the certification criteria. RESULTS: As of October 2015, 228 CPUs in Germany have been successfully certified by the German Cardiac Society; 300 CPUs are needed for full coverage closing gaps in rural regions. Current changes of the criteria mainly affect guideline-adherent adaptions of diagnostic work-ups, therapeutic strategies, risk stratification, in hospital timing and education, and quality measures, whereas the overall structure remained unchanged. Benchmarking by participation within the German CPU registry is encouraged. CONCLUSION: Even though the history is short, the concept of certified CPUs in Germany is accepted and successful underlined by its recent implementation in national and international guidelines. First registry data demonstrated a high standard of quality-of-care. The current update provides rational adaptions to new guidelines and developments without raising the level for successful certifications. A periodic release of fast-track updates with shorter time frames and an increase of minimum requirements should be considered. PMID- 26881819 TI - Economic Deprivation as a Predictor of the Direction of Lethal Violence: An Analysis of Italian Provinces. AB - Research on suicide and homicide rates has neglected an integrated model seeking to explain social variation in the direction of lethal violence. The present investigation explores the association between measures of social deprivation on the relative incidence of suicide over homicide in Italian provinces. Data refer to official government sources on lethal violence rates and measures of social deprivation. The central dependent variable (SHR) is the tendency towards suicide measured as the suicide rate divided by the sum of the suicide and homicide rates. Data were available for 102 Italian provinces in the Census year 2001. The percentage of the population marked by two indicators of deprivation (low education, household population density) were negatively associated with the SHR. The results are largely consistent with a stream of previous research that connects deprivation with a relatively high probability for disadvantaged populations to direct aggression outwardly in the form of homicide rather than inwardly in the form of suicide. The present study specifies which elements of deprivation best predict the direction of violence and is the first study for the Italian context. PMID- 26881820 TI - Reply. PMID- 26881821 TI - Defining an International Standard Set of Outcome Measures for Patients With Hip or Knee Osteoarthritis: Consensus of the International Consortium for Health Outcomes Measurement Hip and Knee Osteoarthritis Working Group. AB - OBJECTIVE: To define a minimum Standard Set of outcome measures and case-mix factors for monitoring, comparing, and improving health care for patients with clinically diagnosed hip or knee osteoarthritis (OA), with a focus on defining the outcomes that matter most to patients. METHODS: An international working group of patients, arthroplasty register experts, orthopedic surgeons, primary care physicians, rheumatologists, and physiotherapists representing 10 countries was assembled to review existing literature and practices for assessing outcomes of pharmacologic and nonpharmacologic OA therapies, including surgery. A series of 8 teleconferences, incorporating a modified Delphi process, were held to reach consensus. RESULTS: The working group reached consensus on a concise set of outcome measures to evaluate patients' joint pain, physical functioning, health related quality of life, work status, mortality, reoperations, readmissions, and overall satisfaction with treatment result. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were defined. Annual outcome measurement is recommended for all patients. CONCLUSION: We have defined a Standard Set of outcome measures for monitoring the care of people with clinically diagnosed hip or knee OA that is appropriate for use across all treatment and care settings. We believe this Standard Set provides meaningful, comparable, and easy to interpret measures ready to implement in clinics and/or registries globally. We view this set as an initial step that, when combined with cost data, will facilitate value-based health care improvements in the treatment of hip and knee OA. PMID- 26881823 TI - Rational Design of NiCoO2@SnO2 Heterostructure Attached on Amorphous Carbon Nanotubes with Improved Lithium Storage Properties. AB - It still remains very challenging to design proper heterostructures to enhance the electrochemical performance of transition metal oxide-based anode materials for lithium-ion batteries. Here, we synthesized the NiCoO2 nanosheets@SnO2 layer heterostructure supported by amorphous carbon nanotubes (ACNTs) which is derived from polymeric nanotubes (PNTs) by a stepwise method. The inner SnO2 layer not only provides a considerable capacity contribution but also produces the extra Li2O to promote the charge process of NiCoO2 and thus results in a rising cycling performance. Combining with the contribution of ACNTs backbone and ultrathin NiCoO2 nanosheets, the specific capacities of these one-dimensional nanostructures show an interesting gradually increasing trend even after 100 cycles at 400 mA g(-1) with a final result of 1166 mAh g(-1). This approach can be an efficient general strategy for the preparation of mixed-metal-oxide one dimensional nanostructures and this innovative design of hybrid electrode materials provides a promising approach for batteries with improved electrochemical performance. PMID- 26881824 TI - Re: Gender Dysphoria and Co-Occurring Autism Spectrum Disorders:Review, Case Examples and Treatment Considerations, by Jacobs et al. (LGBT Health 2014;1:277 282). PMID- 26881822 TI - The Cytolytic Amphipathic beta(2,2)-Amino Acid LTX-401 Induces DAMP Release in Melanoma Cells and Causes Complete Regression of B16 Melanoma. AB - In the present study we examined the ability of the amino acid derivative LTX-401 to induce cell death in cancer cell lines, as well as the capacity to induce regression in a murine melanoma model. Mode of action studies in vitro revealed lytic cell death and release of danger-associated molecular pattern molecules, preceded by massive cytoplasmic vacuolization and compromised lysosomes in treated cells. The use of a murine melanoma model demonstrated that the majority of animals treated with intratumoural injections of LTX-401 showed complete and long-lasting remission. Taken together, these results demonstrate the potential of LTX-401 as an immunotherapeutic agent for the treatment of solid tumors. PMID- 26881825 TI - Bcl-2 proteins in development, health, and disease of the hematopoietic system. AB - Members of the Bcl-2 protein family regulate cell fate decisions following a variety of developmental cues or stress signals, with the outcomes of cell death or survival, thus shaping multiple mammalian tissues. This review describes in detail how anti- and proapoptotic Bcl-2 proteins contribute to the development and functioning of the fetal and adult hematopoietic systems and how they influence the generation and maintenance of different hematopoietic lineages. An overview on how stress signals such as genotoxic stress or inflammation can compromise blood cell production, partially by engaging the intrinsic apoptosis pathway, is presented. Finally, the review describes how Bcl-2 protein deregulation-either leading to increased apoptosis resistance or excessive cell death-contributes to many hematological disorders, with specific focus on rare disorders of hematopoiesis and how this knowledge may be used therapeutically. PMID- 26881826 TI - NaFe3(HPO3)2((H,F)PO2OH)6: A Potential Cathode Material and a Novel Ferrimagnet. AB - A novel iron fluorophosphite, NaFe3(HPO3)2((H,F)PO2OH)6, was synthesized by a dry low-temperature synthesis route. The phase was shown to be electrochemically active for reversible insertion of Na(+) ions, with an average discharge voltage of 2.5 V and an experimental capacity at low rates of up to 90 mAhg(-1). Simple synthesis, low-cost materials, excellent capacity retention, and efficiency suggest this class of material is competitive with similar oxyanion-based compounds as a cathode material for Na batteries. The characterization of physical properties by means of magnetization, specific heat, and electron spin resonance measurements confirms the presence of two magnetically nonequivalent Fe(3+) sites. The compound orders magnetically at TC ~ 9.4 K into a state with spontaneous magnetization. PMID- 26881827 TI - Using atomistic simulations to model cadmium telluride thin film growth. AB - Cadmium telluride (CdTe) is an excellent material for low-cost, high efficiency thin film solar cells. It is important to conduct research on how defects are formed during the growth process, since defects lower the efficiency of solar cells. In this work we use computer simulation to predict the growth of a sputter deposited CdTe thin film. On-the-fly kinetic Monte Carlo technique is used to simulate the CdTe thin film growth on the (1 1 1) surfaces. The results show that on the (1 1 1) surfaces the growth mechanisms on surfaces which are terminated by Cd or Te are quite different, regardless of the deposition energy (0.1~10 eV). On the Te-terminated (1 1 1) surface the deposited clusters first form a single mixed species layer, then the Te atoms in the mixed layer moved up to form a new layer. Whilst on the Cd-terminated (1 1 1) surface the new Cd and Te layers are formed at the same time. Such differences are probably caused by stronger bonding between ad-atoms and surface atoms on the Te layer than on the Cd layer. PMID- 26881829 TI - Approach for 2-(arylthio)imidazoles and imidazo[2,1-b]thiazoles from imidazo[2,1 b][1,3,4]thiadiazoles by ring-opening and -reconstruction. AB - A highly efficient one-pot synthesis of imidazo[2,1-b]thiazole derivatives has been developed and proceeds via a ring-opening and ring-closing reconstruction of imidazo[2,1-b][1,3,4]thiadiazoles with phenylacetylene in the presence of potassium tert-butoxide (t-BuOK) under very mild reaction conditions. A proposed mechanism is calculated computationally using a DFT method at the B3LYP/6 31+G(d,p) level. The imidazo[2,1-b][1,3,4]thiadiazoles are also successfully converted to a series of 2-(arylthio)-1H-imidazoles using aryl halide as a reactant and copper(ii) acetylacetonate (Cu(acac)2) as a catalyst under microwave irradiation conditions. The key features of these reactions are the use of readily available reagents, simple operation, the convenient utilization of new heterocyclic synthons, and a great variety of substrates with functional group compatibility. PMID- 26881830 TI - Spin-Free CC2 Implementation of Induced Transitions between Singlet Ground and Triplet Excited States. AB - In most organic molecules, phosphorescence has its origin in transitions from triplet exited states to the singlet ground state, which are spin-forbidden in nonrelativistic quantum mechanics. A sufficiently accurate description of phosphorescence lifetimes for molecules that contain only light elements can be achieved by treating the spin-orbit coupling (SOC) with perturbation theory (PT). We present an efficient implementation of this approach for the approximate coupled cluster singles and doubles model CC2 in combination with the resolution of-the-identity approximation for the electron repulsion integrals. The induced oscillator strengths and phosphorescence lifetimes from SOC-PT are computed within the response theory framework. In contrast to previous work, we employ an explicitly spin-coupled basis for singlet and triplet operators. Thereby, a spin orbital treatment can be entirely avoided for closed-shell molecules. For compounds containing only light elements, the phosphorescence lifetimes obtained with SOC-PT-CC2 are in good agreement with those of exact two-component (X2C) CC2, whereas the calculations are roughly 12 times faster than with X2C. Phosphorescence lifetimes computed for two thioketones with the SOC-PT-CC2 approach agree very well with reference results from experiment and are similar to those obtained with multireference spin-orbit configuration interaction and with X2C-CC2. An application to phosphorescent emitters for metal-free organic light-emitting diodes (OLEDs) with almost 60 atoms and more than 1800 basis functions demonstrates how the approach extends the applicability of coupled cluster methods for studying phosphorescence. The results indicate that other decay channels like vibrational relaxation may become important in such systems if lifetimes are large. PMID- 26881828 TI - Synthesis of Chiral alpha-Trifluoromethylamines with 2,2,2-Trifluoroethylamine as a "Building Block". AB - The beta-isocupreidine, a cinchonine derived alkaloid, catalyzed asymmetric SN2' SN2' reaction between N-2,2,2-trifluoroethylisatin ketimines and MBH type carbonates was realized in a simple and efficient way. A series of chiral alpha trifluoromethylamines were prepared with excellent yields and stereoselectivities. A subsequent and easy process of deprotection gave gamma trifluoromethyl-alpha-methylenelactam in a stereoselective manner. PMID- 26881832 TI - Pathophysiology of Septic Acute Kidney Injury. AB - BACKGROUND: Despite increased understanding of the pathophysiology of septic acute kidney injury (AKI), treatment options are limited, and mortality remains high. SUMMARY: Septic AKI is triggered by pathogen-associated molecular patterns from bacteria and damage-associated molecular patterns released from or exposed on damaged cells. Downstream effects include glomerular and peritubular endothelial dysfunction, downregulation of tubular reabsorptive work, cell-cycle arrest, regulated cell death and destruction of damaged cell organelles. In the laboratory, pharmacological modulation of some of these pathways prevents AKI or enhances recovery from AKI, yet no data exist to support the utility of such AKI therapy in man. However, avoiding systemic and renal venous congestion, hypotension and fluid overload attenuates AKI in critically ill septic patients. KEY MESSAGE: While therapies aiming at modulating the sepsis-induced cellular response are discovered and tested, hemodynamic optimization remains critical in patients with or at risk of AKI. PMID- 26881831 TI - Pediatric Chordomas: A Population-Based Clinical Outcome Study Involving 86 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011). AB - BACKGROUND/AIMS: Primary chordomas, rare cancers arising from the notochord remnants, are extremely rare in the pediatric population. This study examined a large cohort of primary chordoma patients to determine factors impacting prognosis and survival. METHODS: Demographic and clinical data on 1,358 primary chordoma patients (86 pediatric patients <=19 years of age and 1,272 adult patients >=20 years of age) were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database (1973-2011). RESULTS: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite the majority of primary chordomas presenting with locoregional involvement (90.4%), pediatric patients had more distant disease (14.8 vs. 9.2%, p < 0.05). Survival among pediatric patients having surgery only was significantly longer than for adults (22.5 vs. 14.3 years, p < 0.001). Overall survival was longer (17.2 vs. 12.6 years) and overall mortality was lower in pediatric patients (38.4 vs. 49.8%), but cancer-specific mortality was higher (37.2 vs. 28.6%, p < 0.005). CONCLUSIONS: Pediatric primary chordomas present most often as small tumors <4 cm in the cranium of male Caucasians. Despite having a higher rate of metastasis, they have prolonged survival compared to adults. Surgical resection significantly improves survival in pediatric primary chordoma patients, and should be considered as first-line therapy in all eligible children. PMID- 26881833 TI - Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study. AB - Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48+/ 16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% +/-7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance. PMID- 26881835 TI - Hair cortisol and cognitive performance in working age adults. AB - It has been hypothesized that prolonged exposure to high cortisol levels results in cognitive impairment. However, previous research into the relationship between cortisol and cognition has produced mixed results, most likely due to difficulties achieving valid estimates of long-term cortisol exposure based on salivary or plasma cortisol assessments at a single time point. Furthermore, there has been little research on the cognitive effects of long-term cortisol exposure in working-age adults. In the present study, hair samples were collected from 246 nurses (89.8% female) aged from 21 to 62 (M=42.0, SD=11.2). Hair cortisol concentrations (HCC) in the proximal 3-cm hair segment were analyzed providing an estimate of integrated cortisol secretion over the 3 month-period prior to hair sampling. Cognition was measured using a battery of 15 neuropsychological tests, measuring core dimensions of memory, inductive reasoning, processing speed, crystalized intelligence and major aspects of executive functioning. HCC was not significantly related to any of the cognitive abilities measured, either before or after controlling for potential moderators such as age, sex, education, health, well-being, work ability and burnout. Tests for nonlinear relationships also yielded non-significant results. Thus, despite the study being well powered, long term cortisol exposure did not appear to be related to cognitive performance in this sample of working-age adults, suggesting that long term cortisol exposure may be less relevant to cognition in younger and middle-aged adults than was previously thought. PMID- 26881834 TI - Early life stress dampens stress responsiveness in adolescence: Evaluation of neuroendocrine reactivity and coping behavior. AB - Stressful experiences during early life (ELS) can affect brain development, thereby exerting a profound and long-lasting influence on mental development and psychological health. The stress inoculation hypothesis presupposes that individuals who have early experienced an attenuated form of stressors may gain immunity to its more virulent forms later in life. Increasing evidence demonstrates that ELS may promote the development of subsequent stress resistance, but the mechanisms underlying such adaptive changes are not fully understood. The present study evaluated the impact of fragmented dam-pup interactions by limiting the bedding and nesting material in the cage during postnatal days 2-9, a naturalistic animal model of chronic ELS, on the physiological and behavioral responses to different stressors in adolescent mice and characterized the possible underlying mechanisms. We found that ELS mice showed less social interaction deficits after chronic social defeat stress and acute restraint-tailshock stress-induced impaired long-term potentiation (LTP) and enhanced long-term depression (LTD) in hippocampal CA1 region compared with control mice. The effects of ELS on LTP and LTD were rescued by adrenalectomy. While ELS did not cause alterations in basal emotional behaviors, it significantly enhanced stress coping behaviors in both the tail suspension and the forced swimming tests. ELS mice exhibited a significant decrease in corticosterone response and trafficking of glucocorticoid receptors to the nucleus in response to acute restraint stress. Altogether, our data support the hypothesis that stress inoculation training, via early exposure to manageable stress, may enhance resistance to other unrelated extreme stressors in adolescence. PMID- 26881836 TI - Acute restraint stress induces rapid changes in central redox status and protective antioxidant genes in rats. AB - The stress-induced imbalance in reduction/oxidation (redox) state has been proposed to play a major role in the etiology of neurological disorders. However, the relationship between psychological stress, central redox state, and potential protective mechanisms within specific neural regions has not been well characterized. In this study, we have used an acute psychological stress to demonstrate the dynamic changes that occur in the redox system of hippocampal and striatal tissue. Outbred male Wistar rats were subject to 0 (control), 60, 120, or 240min of acute restraint stress and the hippocampus and striatum were cryodissected for redox assays and relative gene expression. Restraint stress significantly elevated oxidative status and lipid peroxidation, while decreasing glutathione ratios overall indicative of oxidative stress in both neural regions. These biochemical changes were prevented by prior administration of the glucocorticoid receptor antagonist, RU-486. The hippocampus also demonstrated increased glutathione peroxidase 1 and 4 antioxidant expression which was not observed in the striatum, while both regions displayed robust upregulation of the antioxidant, metallothionein 1a. This was observed with concurrent upregulation of 11beta-hydroxysteroid dehydrogenase 1, a local reactivator of corticosterone, in addition to decreased expression of the cytosolic regulatory subunit of superoxide-producing enzyme, NADPH-oxidase. Together, this study demonstrates distinctive regional redox profiles following acute stress exposure, in addition to identifying differential capabilities in managing oxidative challenges via altered antioxidant gene expression in the hippocampus and striatum. PMID- 26881837 TI - Decline of hippocampal stress reactivity and neuronal ensemble coherence in a mouse model of depression. AB - Dysregulations of stress systems, especially the hypothalamo-pituitary-adrenal (HPA) axis, have been commonly reported in major depression. Consistent results emphasized the role of the hippocampus in regulating stress systems and restoring an operative control on HPA axis following antidepressant treatments. However, very little is known about how the hippocampus integrates stress-related information and reacts to stressors beforehand. We therefore aimed to assess activations of hippocampal neuronal ensembles during stress-related experiences and evaluated the effects of a mouse model of depression, the Unpredictable Chronic Mild Stress (UCMS), and an antidepressant treatment (fluoxetine, 20mgkg( 1)day(-1), ip) in BALB/cByJ mice. The UCMS induced a depression-like syndrome characterized by a reduced weight gain, a progressive deterioration of the coat, an altered stress-coping strategy in behavioural tests and HPA axis dysregulations. Chronic fluoxetine had no effect in control non-stressed mice per se but reversed the syndrome induced by the UCMS, including an improvement of the HPA-system alterations. Neuronal activation was then assessed by immediate early gene (c-fos) expression in different subfields of the CA3 and dentate gyrus (DG) along the dorso-ventral axis of the hippocampus, as they can support different computational functions. Our results showed that the hippocampus reacts to stressors by adjusting activations of cell ensembles. A pre-treatment with dexamethasone (DEX), a glucocorticoid receptor (GR) agonist that produced a delayed inhibition of the HPA axis activity, reduced novelty-related activations in the proximal CA3 (CA3c) and the DG of the dorsal hippocampus. All these effects were compromised by the UCMS, particularly by altering activation coherences within the dorsal CA3-DG network, but were rescued by chronic fluoxetine. Our study indicates therefore that variations of CA3-DG cell ensemble activation may contribute to stress integration in the hippocampus and that dysfunctions of this process may foster HPA-system dysregulations and depression related states. It suggests that pharmacological interventions aiming to consolidate CA3-DG neural network might improve stress reactivity and possibly benefit to patients with major depression. PMID- 26881838 TI - How to treat paracetamol overdose and when to do it. PMID- 26881840 TI - Rearing history and allostatic load in adult western lowland gorillas (Gorilla gorilla gorilla) in human care. AB - Disrupted rearing history is a psychological and physical stressor for nonhuman primates, potentially resulting in multiple behavioral and physiological changes. As a chronic, soma-wide stressor, altered rearing may be best assessed using a holistic tool such as allostatic load (AL). In humans, AL estimates outcomes of lifetime stress-induced damage. We predicted mother-reared gorillas would have lower AL than nursery-reared and wild-caught conspecifics. We estimated AL for 27 gorillas housed at the Columbus Zoo and Aquarium between 1956 and 2014. AL estimates were calculated using biomarkers obtained during previous anesthetic events. Biomarkers in the high-risk quartile were counted toward a gorilla's AL. Rearing history was categorized as mother-reared, nursery-reared, and wild caught. Using ANCOVA, rearing history and AL are significantly associated when age and sex are entered as covariates. Wild-caught gorillas have significantly higher AL than mother-reared gorillas. Neither wild-caught nor mother-reared gorillas are significantly different from nursery-reared gorillas. When examined by sex, males of all rearing histories have significantly lower AL than females. We suggest males face few stressors in human care and ill effects of rearing history do not follow. Wild-caught females have significantly higher AL than mother-reared females, but neither is significantly different from nursery-reared females. Combined with our previous work on AL in this group, wherein females had twofold higher AL than males, we suggest females in human care face more stressors than males. Disrupted rearing history may exacerbate effects of these stressors. Providing opportunities for females to choose their distance from males may help reduce their AL. PMID- 26881839 TI - Parallel effects of the inversion In(3R)Payne on body size across the North American and Australian clines in Drosophila melanogaster. AB - Chromosomal inversions are thought to play a major role in climatic adaptation. In D. melanogaster, the cosmopolitan inversion In(3R)Payne exhibits latitudinal clines on multiple continents. As many fitness traits show similar clines, it is tempting to hypothesize that In(3R)P underlies observed clinal patterns for some of these traits. In support of this idea, previous work in Australian populations has demonstrated that In(3R)P affects body size but not development time or cold resistance. However, similar data from other clines of this inversion are largely lacking; finding parallel effects of In(3R)P across multiple clines would considerably strengthen the case for clinal selection. Here, we have analysed the phenotypic effects of In(3R)P in populations originating from the endpoints of the latitudinal cline along the North American east coast. We measured development time, egg-to-adult survival, several size-related traits (femur and tibia length, wing area and shape), chill coma recovery, oxidative stress resistance and triglyceride content in homokaryon lines carrying In(3R)P or the standard arrangement. Our central finding is that the effects of In(3R)P along the North American cline match those observed in Australia: standard arrangement lines were larger than inverted lines, but the inversion did not influence development time or cold resistance. Similarly, In(3R)P did not affect egg-to adult survival, oxidative stress resistance and lipid content. In(3R)P thus seems to specifically affect size traits in populations from both continents. This parallelism strongly suggests an adaptive pattern, whereby the inversion has captured alleles associated with growth regulation and clinal selection acts on size across both continents. PMID- 26881842 TI - The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis. AB - BACKGROUND: The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear. PURPOSE: To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis. DATA SOURCES: Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening. STUDY SELECTION: Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics. DATA EXTRACTION: Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the Short Form-36 Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools. DATA SYNTHESIS: Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients. LIMITATION: Statistically significant heterogeneity among studies, few good quality studies, and possible publication bias. CONCLUSION: ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD. PRIMARY FUNDING SOURCE: KRESCENT and Manitoba Health Research Council Establishment. PMID- 26881841 TI - AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy. AB - Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken beta-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder. PMID- 26881844 TI - Multiresidue Analysis of Pesticides in Straw Roughage by Liquid Chromatography Tandem Mass Spectrometry. AB - A multiresidue analytical method using a modification of the "quick, easy, cheap, effective, rugged, and safe" (QuEChERS) sample preparation approach combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was established and validated for the rapid determination of 69 pesticides at different levels (1-100 ng/g) in wheat and rice straws. In the quantitative analysis, the recoveries ranged from 70 to 120%, and consistent RSDs <= 20% were achieved for most of the target analytes (53 pesticides in wheat straw and 58 in rice straw). Almost all of the analytes achieved good linearity with R(2) > 0.98, and the limit of validation levels (LVLs) for diverse pesticides ranged from 1 to 10 ng/g. Different extraction and cleanup conditions were evaluated in both types of straw, leading to different options. The use of 0.1% formic acid or not in extraction with acetonitrile yielded similar final outcomes, but led to the use of a different sorbent in dispersive solid-phase extraction. Both options are efficient and useful for the multiresidue analysis of targeted pesticides in wheat and rice straw samples. PMID- 26881843 TI - Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes. AB - The quality of mammalian oocytes declines with age, which negatively affects fertilization and developmental potential. The aging process often accompanies damages to macromolecules such as proteins, DNA, and lipids. To investigate if aged oocytes display an altered lipidome compared to young oocytes, we performed a global lipidomic analysis between oocytes from 4-week-old and 42 to 50-week-old mice. Increased oxidative stress is often considered as one of the main causes of cellular aging. Thus, we set up a group of 4-week-old oocytes treated with hydrogen peroxide (H2O2), a commonly used oxidative stressor, to compare if similar lipid species are altered between aged and oxidative-stressed oocytes. Between young and aged oocytes, we identified 26 decreased and 6 increased lipids in aged oocytes; and between young and H2O2-treated oocytes, we identified 35 decreased and 26 increased lipids in H2O2-treated oocytes. The decreased lipid species in these two comparisons were overlapped, whereas the increased lipid species were distinct. Multiple phospholipid classes, phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylserine (PS), and lysophosphatidylserine (LPS) significantly decreased both in H2O2-treated and aged oocytes, suggesting that the integrity of plasma membrane is similarly affected under these conditions. In contrast, a dramatic increase in diacylglycerol (DG) was only noted in H2O2-treated oocytes, indicating that the acute effect of H2O2-caused oxidative stress is distinct from aging-associated lipidome alteration. In H2O2 treated oocytes, the expression of lysophosphatidylcholine acyltransferase 1 increased along with increases in phosphatidylcholine. Overall, our data reveal that several classes of phospholipids are affected in aged oocytes, suggesting that the integrity of plasma membrane is associated with maintaining fertilization and developmental potential of mouse oocytes. PMID- 26881845 TI - Revisiting Adiabatic Switching for Initial Conditions in Quasi-Classical Trajectory Calculations: Application to CH4. AB - Semiclassical quantization of vibrational energies, using adiabatic switching (AS), is applied to CH4 using a recent ab initio potential energy surface, for which exact quantum calculations of vibrational energies are available. Details of the present calculations, which employ a harmonic normal-mode zeroth-order Hamiltonian, emphasize the importance of transforming to the Eckart frame during the propagation of the adiabatically switched Hamiltonian. The AS energies for the zero-point, and fundamental excitations of two modes are in good agreement with the quantum ones. The use of AS in the context of quasi-classical trajectory calculations is revisited, following previous work reported in 1995, which did not recommend the procedure. We come to a different conclusion here. PMID- 26881846 TI - The Future of Diabetes Prevention: A Call for Papers. PMID- 26881847 TI - Octopus vulgaris (Cuvier, 1797) in the Mediterranean Sea: Genetic Diversity and Population Structure. AB - The common octopus, Octopus vulgaris Cuvier 1797, is a largely exploited cephalopod species in the Mediterranean Sea and the Atlantic Ocean, as well as along the coasts of Africa, Brazil and Japan, where its taxonomic identity is still debated. The assessment of its genetic structure is a pressing need to correctly manage the resource and to avoid overfishing and collapsing of local stocks. Here we analysed genetic variation and population structure of O. vulgaris using thirteen microsatellite loci in seven sampling localities from the Mediterranean Sea and one from the Atlantic Ocean. We also used a DNA barcoding approach by COI gene fragment to understand the phylogenetic relationships among the specimens here investigated and the ones whose sequences are available in literature. Our results reveal high levels of allelic richness and moderate heterozygosity in all samples investigated, and a pronounced differentiation of the Atlantic and Sicilian specimens. This latter aspect seems to support the isolation of the biota within the Strait of Messina. A certain degree of differentiation was detected among the other geographic samples within the Mediterranean Sea, which is more compatible with an island model than isolation by distance. The occurrence of null alleles affected more genetic diversity indices than population structure estimations. This study provides new insights about the genetic diversity and structure of O. vulgaris in the area of interest, which can be used as guidelines for a fisheries management perspective. PMID- 26881848 TI - Oral health-related knowledge, attitudes and habits in relation to perceived oral symptoms among 12-year-old school children. AB - Objective The aim of the study was to investigate oral health-related knowledge, attitudes and habits and their relationship to perceived oral symptoms among 12 year-olds and differences between boys and girls. Material and methods The study population consisted of children (n = 588) in 15 randomly selected elementary schools in Turku, Finland. Associations between oral health-related habits, knowledge and attitudes with perceived oral symptoms and gender differences were evaluated with chi(2)-test, Mann-Whitney U-test and logistic regression analysis. Results Oral health promoting habits but not knowledge or attitudes associated significantly with absence of oral symptoms. Girls reported a higher percentage of several health promotional habits than boys. Girls reported more frequently gingival bleeding and less frequently dental calculus than boys did. The most common oral symptom was gingival bleeding. Conclusions The present findings suggest some gender-related differences in oral health habits, attitudes, as well as perceived oral symptoms in 12-year-olds. There seems, however, not to be gender differences in relation to knowledge or the association of health habits with perceived oral symptoms. It is important to maintain health promotion at schools and additional efforts should be aimed at translating knowledge into action. PMID- 26881849 TI - Conformational Disorganization within the Active Site of a Recently Evolved Organophosphate Hydrolase Limits Its Catalytic Efficiency. AB - The evolution of new enzymatic activity is rarely observed outside of the laboratory. In the agricultural pest Lucilia cuprina, a naturally occurring mutation (Gly137Asp) in alpha-esterase 7 (LcalphaE7) results in acquisition of organophosphate hydrolase activity and confers resistance to organophosphate insecticides. Here, we present an X-ray crystal structure of LcalphaE7:Gly137Asp that, along with kinetic data, suggests that Asp137 acts as a general base in the new catalytic mechanism. Unexpectedly, the conformation of Asp137 observed in the crystal structure obstructs the active site and is not catalytically productive. Molecular dynamics simulations reveal that alternative, catalytically competent conformers of Asp137 are sampled on the nanosecond time scale, although these states are less populated. Thus, although the mutation introduces the new reactive group responsible for organophosphate detoxification, the catalytic efficiency appears to be limited by conformational disorganization: the frequent sampling of low-energy nonproductive states. This result is consistent with a model of molecular evolution in which initial function-changing mutations can result in enzymes that display only a fraction of their catalytic potential due to conformational disorganization. PMID- 26881850 TI - Tuberculosis Mortality and Living Conditions in Bern, Switzerland, 1856-1950. AB - BACKGROUND: Tuberculosis (TB) is a poverty-related disease that is associated with poor living conditions. We studied TB mortality and living conditions in Bern between 1856 and 1950. METHODS: We analysed cause-specific mortality based on mortality registers certified by autopsies, and public health reports 1856 to 1950 from the city council of Bern. RESULTS: TB mortality was higher in the Black Quarter (550 per 100,000) and in the city centre (327 per 100,000), compared to the outskirts (209 per 100,000 in 1911-1915). TB mortality correlated positively with the number of persons per room (r = 0.69, p = 0.026), the percentage of rooms without sunlight (r = 0.72, p = 0.020), and negatively with the number of windows per apartment (r = -0.79, p = 0.007). TB mortality decreased 10-fold from 330 per 100,000 in 1856 to 33 per 100,000 in 1950, as housing conditions improved, indoor crowding decreased, and open-air schools, sanatoria, systematic tuberculin skin testing of school children and chest radiography screening were introduced. CONCLUSIONS: Improved living conditions and public health measures may have contributed to the massive decline of the TB epidemic in the city of Bern even before effective antibiotic treatment became finally available in the 1950s. PMID- 26881851 TI - Smoking, cessation, and cessation counseling in patients with cancer: A population-based analysis. AB - BACKGROUND: Smoking is known to be carcinogenic and an important factor in the outcome of cancer treatment. However, to the authors' knowledge, smoking habits and smoking cessation counseling in patients with cancer have been poorly studied. The authors sought to analyze smoking habits among Americans diagnosed with cancer in a nationally representative dataset. METHODS: The cancer supplement of the National Health Interview Survey (NHIS) in 2010 was used to obtain information regarding self-reported smoking behavior in a representative sample of the US population. Cancer history, smoking history, quitting behavior, cessation counseling, cessation approaches, and sociodemographic variables were analyzed. RESULTS: A total of 27,157 individuals were interviewed for the NHIS in 2010, representing 216,052,891 individuals, 7,058,135 of whom had ever smoked and 13,188,875 of whom had been told that they had cancer. Approximately 51.7% of individuals diagnosed with cancer and who were active smokers reported being counseled to quit smoking by a health professional within the previous 12 months. Cancer survivors were no more likely to quit smoking than individuals in the general population. Those diagnosed with a tobacco-related cancer were found to be no more likely to report quitting smoking than those with other types of cancers. Rates of quitting did not appear to vary based on the type of smoking cessation method used (P = .50). CONCLUSIONS: Patients with cancer, including those diagnosed with a tobacco-related cancer, do not appear to be more likely to quit smoking than the general population. Only approximately one-half of patients with cancer who smoke are counseled to quit. Smoking cessation in patients with cancer is an important area for intervention and investigation. PMID- 26881852 TI - The windblown hand and its surgical management. PMID- 26881853 TI - Anticoagulant, antiplatelet and antianemic effects of Punica granatum (pomegranate) juice in rabbits. AB - Pomegranate (Punica granatum L., Punicaceae) is a good source of minerals and phytochemicals with diverse pharmacological activities such as anxiolytic, antidepressant, hypoglycemic, hypolipidemic, and anti-inflammatory activities. Effects of P. granatum on blood parameters and coagulation have, however, been little studied. The aim of the study was to assess the outcome of P. granatum on coagulation and anticoagulation factors at different doses on blood samples of healthy white rabbits. Blood samples of the animals were collected twice during the study and biochemical assays were performed to assess the effect on hematological, coagulation, anticoagulation, and platelet aggregation. Significant changes were observed in erythrocytes, hemoglobin, and mean corpuscular hemoglobin concentration, while bleeding and thrombin time were also prolonged significantly. There was significant increase in protein C, thrombin antithrombin complex levels, and decrease in platelet aggregation and fibrinogen concentration, in a dose-dependent manner. The results of hematological and coagulation assays lead to the speculation about a possible antianemic and cardioprotective effect of P. granatum. PMID- 26881854 TI - An observational study of haemostatic changes, leptin and soluble endoglin during pregnancy in women with different BMIs. AB - Obesity increases the risk of venous thromboembolism (VTE) in pregnancy. The pathogenesis is hypothesized to be because of multiple factors including prothrombotic changes, but there has been minimal haemostatic research looking at the combined state of obesity and pregnancy. We aimed to determine whether variation in BMI in the third trimester of pregnancy was associated with prothrombotic changes. We recruited 110 women into four groups depending on their BMI at first antenatal appointment: normal, overweight, obese and morbidly obese. Women with increased risk of VTE, and/or receiving thromboprophylaxis, and/or more than 35 years and those in labour were excluded. Thromboelastography, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin fragment 1 + 2, free and total protein S, plasminogen activator inhibitor type 1, tissue plasminogen activator antigen, D-dimers, soluble endoglin and leptin levels were measured. There were no significant differences in haemostatic measures with changing BMI. There was a positive correlation between BMI and both platelet count (correlation coefficient r = 0.214, P = 0.036) and leptin (r = 0.435, P < 0.001), but only leptin had a significant association with BMI once adjusted for age, gestation and parity. Despite recruitment into the morbidly obese group being suboptimal, these findings suggest that in pregnancy, the increased risk of VTE seen in obese mothers is not mediated through increased prothrombotic changes, and thus the increased risk of VTE in obese pregnant women may be because of other mechanisms, for example endothelial dysfunction, inflammation and venous stasis. PMID- 26881855 TI - A novel coagulation parameter monitoring bleeding tendency of Chinese nonvalvular atrial fibrillation patients prescribing dabigatran etexilate. AB - The objective of this study was to find a new parameter to monitor bleeding tendency after dabigatran etexilate (Pradaxa) medication in Chinese nonvalvular atrial fibrillation patients. Blood samples of 231 nonvalvular atrial fibrillation patients were collected and five routine coagulation examinations (prothrombin time/International normalized ratio, activated partial thromboplastin time, fibrinogen assay, thrombin time and D-dimer) were assayed. After dabigatran etexilate administration, prolonged activated partial thromboplastin time and thrombin time were observed, especially TT. Derived parameter DeltaTT (TT after dabigatran etexilate medication - TT before dabigatran etexilate medication) of bleeding patients was higher than nonbleeding patients (97.7 vs. 85.6 s, P = 0.038). When using DeltaTT to distinguish patients with and without bleeding events, the cutoff value was 97.25 s, where sensitivity was 82.4% and specificity was 50.0%. The area under the curve was 0.786. TT is better than other routine coagulation parameters in monitoring the effect of dabigatran etexilate. DeltaTT can distinguish bleeding patients from nonbleeding patients. PMID- 26881856 TI - Angiotensin-Converting Enzyme Inhibitor (ACEI)-Mediated Amelioration in Renal Fibrosis Involves Suppression of Mast Cell Degranulation. AB - BACKGROUND/AIMS: The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs) attenuate renal fibrosis has not been fully uncovered. METHODS: Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO) and treated with Enalapril. RESULTS: Enalapril attenuated renal fibrosis, as evidenced by the fibrosis scores (1.07+/-0.73 versus 2.18+/-0.75 for 200 mg/ml Enalapril versus control, p<0.01) of Enalapril-treated UUO rats compared to mock treated UUO rats. The amelioration was mast cell dependent, as Enalapril exhibited no effects on mast cell-deficient Kit(wsh/wsh) mice developing renal fibrosis. We detected lower levels of transforming growth factor beta (TGF-beta) and alpha-smooth muscle actin (alpha-SMA, a fibroblast activation marker) in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00+/-0.65 versus 29.00+/-0.57, p<0.01). Electron microscopy images revealed that mast cell degranulation was inhibited by Enalapril treatment. Further, IgE-mediated passive cutaneous anaphylaxis demonstrated that Enalapril blocked mast cell degranulation in vivo. CONCLUSION: Enalapril attenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation. PMID- 26881857 TI - Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway. AB - Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5 AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5mg/ml for 20 min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-alpha, CCL-2 and KC, but not interleukin (IL)-1beta in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5mg/ml was comparable to that of ambroxol at 20mg/kg i.v. and dexamethasone at 0.5mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20 MUM inhibited the CSE induced up-regulation of MUC5AC, TNF-alpha, IL-1beta mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy. PMID- 26881859 TI - Pharmacotherapy of Aggression in Child and Adolescent Psychiatric Disorders. AB - OBJECTIVE: Aggression is a common, yet complex, behavioral complaint, and a frequent indication for referral to child and adolescent psychiatrist treatment. This article reviews the evidence supporting pharmacotherapy of aggression in youth, with a primary focus on impulsive aggression (the primary indication for this intervention). Relevant diagnostic considerations and consensus guidelines are discussed. METHODS: Articles examining the role of medications in the treatment of aggression in youth with pathological aggression were identified using PubMed and MEDLINE(r) databases over the past 15 years (2000-2015); selected articles published prior to 2000 and deemed to be of high relevance were searched and also included. Search terms included: Aggression, aggressive, disruptive behavior, conduct, youth, children, and adolescents. Cited references were also searched for relevant articles. RESULTS: There are a number of evidence based medication treatments for aggression, which are generally best considered in the context of differential diagnosis and ongoing evidence-based psychosocial interventions. Impulsive aggression is generally considered the type of aggression most amenable to medication, but other aggression subtypes may also possibly respond to treatment. Medication classes with positive evidence include the psychostimulants and alpha-2 agonists (in the presence of attention deficit/hyperactivity disorder [ADHD] and/or disruptive behavior disorders), mood stabilizing agents, and atypical antipsychotics. Published guidelines recommend systematic and adequate trials of medications in sequential order, to optimize response and minimize polypharmacy. Guidelines for safety monitoring are available for many of the medications used for aggression in youth, and are also discussed. CONCLUSIONS: Aggression in children carries a high risk of poor outcomes, and, therefore, a better understanding of treatment options is a high priority. The available literature points to the importance of identifying the underlying disorder, when possible, and using this information to guide treatment selection. Future studies are needed to better inform the treatment of aggression across disorders, and the treatment of different aggression subtypes. PMID- 26881860 TI - Staying Up at Night: Overlapping Bipolar and Obsessive-Compulsive Disorder Symptoms in an Adolescent with Autism Spectrum Disorder. PMID- 26881861 TI - Weight Loss Associated with Reboxetine Use in Adolescents. PMID- 26881862 TI - Putting the Spotlight on Invisible Family Caregivers. PMID- 26881864 TI - Management of Cardiac Surgery-Associated Acute Kidney Injury. AB - Cardiac surgery-associated acute kidney injury (CSA-AKI) is known to be a common complication of cardiac surgery that is associated with poor short- and long-term outcomes. The causes of CSA-AKI include the discovered or undiscovered risk factors within the perioperative course, mostly non-modifiable; some are even iatrogenic. Recognizing and mediating risk factors preoperatively and optimizing intraoperative practices may decrease the incidence of CSA-AKI. By now, the present studies cannot confirm which drugs are better off for preventing CSA-AKI. The effect and whether early administration of these drugs to prevent CSA-AKI is effective remain uncertain, so is the administration of renal replacement therapy. We will demonstrate some typical studies that focus on the prevention of CSA-AKI and may delight further research. PMID- 26881865 TI - An attentional bias for LEGO(r) people using a change detection task: Are LEGO(r) people animate? AB - Animate objects have been shown to elicit attentional priority in a change detection task. This benefit has been seen for both human and nonhuman animals compared with inanimate objects. One explanation for these results has been based on the importance animate objects have served over the course of our species' history. In the present set of experiments, we present stimuli, which could be perceived as animate, but with which our distant ancestors would have had no experience, and natural selection could have no direct pressure on their prioritization. In the first experiment, we compared LEGO(r) "people" with LEGO "nonpeople" in a change detection task. In a second experiment, we attempt to control the heterogeneity of the nonanimate objects by using LEGO blocks, matched in size and colour to LEGO people. In the third experiment, we occlude the faces of the LEGO people to control for facial pattern recognition. In the final 2 experiments, we attempt to obscure high-level categorical information processing of the stimuli by inverting and blurring the scenes. (PsycINFO Database Record PMID- 26881863 TI - Low Interferon Relative-Response to Cytomegalovirus Is Associated with Low Likelihood of Intrauterine Transmission of the Virus. AB - BACKGROUND: Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe mental and hearing impairments. Notably, only 40% of primarily infected women transmit CMV to the fetus. CMV-specific T-cell response has a role in CMV disease but individual immune heterogeneity precludes reliable correlation between measurable T-cells response and intrauterine transmission. STUDY AIM: To establish a correlation between maternal T-cells response and fetal CMV transmission using an individual normalized immune response. METHODS: We analyzed IFN-gamma secretion upon whole blood stimulation from primary CMV-infected pregnant women, with either CMV-peptides or PHA mitogen. RESULTS: We established a new normalization method of individual IFN gamma response to CMV by defining the ratio between specific-CMV response and non specific mitogen response (defined as IFN-gamma relative response, RR), aiming to overcome high person-to-person immune variability. We found a unique subpopulation of women with low IFN-gamma RR strongly correlated with absence of transmission. IFN-gamma RR lower than 1.8% (threshold determined by ROC analysis) reduces the pre-test probability of transmission from 40% to 8%, revealing an unexpected link between low IFN-gamma RR and non-transmission. CONCLUSION: In pregnant women with primary CMV infection, low IFN-gamma RR is associated with low risk of transmission. PMID- 26881866 TI - Classification of Cholestatic and Necrotic Hepatotoxicants Using Transcriptomics on Human Precision-Cut Liver Slices. AB - Human toxicity screening is an important stage in the development of safe drug candidates. Hepatotoxicity is one of the major reasons for the withdrawal of drugs from the market because the liver is the major organ involved in drug metabolism, and it can generate toxic metabolites. There is a need to screen molecules for drug-induced hepatotoxicity in humans at an earlier stage. Transcriptomics is a technique widely used to screen molecules for toxicity and to unravel toxicity mechanisms. To date, the majority of such studies were performed using animals or animal cells, with concomitant difficulty in interpretation due to species differences, or in human hepatoma cell lines or cultured hepatocytes, suffering from the lack of physiological expression of enzymes and transporters and lack of nonparenchymal cells. The aim of this study was to classify known hepatotoxicants on their phenotype of toxicity in humans using gene expression profiles ex vivo in human precision-cut liver slices (PCLS). Hepatotoxicants known to induce either necrosis (n = 5) or cholestasis (n = 5) were used at concentrations inducing low (<30%) and medium (30-50%) cytotoxicity, based on ATP content. Random forest and support vector machine algorithms were used to classify hepatotoxicants using a leave-one-compound-out cross-validation method. Optimized biomarker sets were compared to derive a consensus list of markers. Classification correctly predicted the toxicity phenotype with an accuracy of 70-80%. The classification is slightly better for the low than for the medium cytotoxicity. The consensus list of markers includes endoplasmic reticulum stress genes, such as C2ORF30, DNAJB9, DNAJC12, SRP72, TMED7, and UBA5, and a sodium/bile acid cotransporter (SLC10A7). This study shows that human PCLS are a useful model to predict the phenotype of drug-induced hepatotoxicity. Additional compounds should be included to confirm the consensus list of markers, which could then be used to develop a biomarker PCR-array for hepatotoxicity screening. PMID- 26881867 TI - Transcriptome regulation and chromatin occupancy by E2F3 and MYC in mice. AB - E2F3 and MYC are transcription factors that control cellular proliferation. To study their mechanism of action in the context of a regenerating tissue, we isolated both proliferating (crypts) and non-dividing (villi) cells from wild type and Rb depleted small intestines of mice and performed ChIP-exo-seq (chromatin immunoprecipitation combined with lambda exonuclease digestion followed by high-throughput sequencing). The genome-wide chromatin occupancy of E2F3 and MYC was determined by mapping sequence reads to the genome and predicting preferred binding sites (peaks). Binding sites could be accurately identified within small regions of only 24 bp-28 bp long, highlighting the precision to which binding peaks can be identified by ChIP-exo-seq. Forty randomly selected E2F3- and MYC-specific binding sites were validated by ChIP PCR. In addition, we also presented gene expression data sets from wild type, Rb , E2f3- and Myc-depleted crypts and villi within this manuscript. These represent comprehensive and validated datasets that can be integrated to identify putative direct targets of E2F3 and MYC involved in the control of cellular proliferation in normal and Rb-deficient small intestines. PMID- 26881868 TI - A strontium-incorporated nanoporous titanium implant surface for rapid osseointegration. AB - Rapid osseointegration of dental implants will shorten the period of treatment and enhance the comfort of patients. Due to the vital role of angiogenesis played during bone development and regeneration, it might be feasible to promote rapid osseointegration by modifying the implant surface to gain a combined angiogenesis/osteogenesis inducing capacity. In this study, a novel coating (MAO Sr) with strontium-incorporated nanoporous structures on titanium implants was generated via a new micro-arc oxidation, in an attempt to induce angiogenesis and osteogenesis to enhance rapid osseointegration. In vitro, the nanoporous structure significantly enhanced the initial adhesion of canine BMSCs. More importantly, sustained release of strontium ions also displayed a stronger effect on the BMSCs in facilitating their osteogenic differentiation and promoting the angiogenic growth factor secretion to recruit endothelial cells and promote blood vessel formation. Advanced mechanism analyses indicated that MAPK/Erk and PI3K/Akt signaling pathways were involved in these effects of the MAO-Sr coating. Finally, in the canine dental implantation study, the MAO-Sr coating induced faster bone formation within the initial six weeks and the osseointegration effect was comparable to that of the commercially available ITI implants. These results suggest that the MAO-Sr coating has the potential for future use in dental implants. PMID- 26881869 TI - Exploring Summer Medical Care Within the National Collegiate Athletic Association Division I Setting: A Perspective From the Athletic Trainer. AB - CONTEXT: Over the last few decades, the National Collegiate Athletics Association (NCAA) has made changes related to the increase in sanctioned team activities during summer athletics. These changes may affect how athletic training services are provided. OBJECTIVE: To investigate the methods by which athletic training departments of NCAA institutions manage expectations regarding athletic training services during the summer. DESIGN: Mixed-methods qualitative and quantitative study. SETTING: The NCAA Division I. PATIENTS OR OTHER PARTICIPANTS: Twenty-two athletic trainers (13 men, 9 women) participated. All were employed full time within the NCAA Division I setting. Participants were 35 +/- 8 years of age (range, 26-52 years), with 12 +/- 7 years (range, 3-29 years) of athletic training experience. DATA COLLECTION AND ANALYSIS: All participants completed a series of questions online that consisted of closed- (demographic and Likert scale 5-point) and open-ended items that addressed the research questions. Descriptive statistics, frequency distributions, and phenomenologic analyses were completed with the data. Peer review and multiple-analyst triangulation established credibility. RESULTS: Summer athletic training services included 3 primary mechanisms: individual medical care, shared medical care, or a combination of the 2. Participants reported working 40 +/- 10 hours during the summer. Likert-item analysis showed that participants were moderately satisfied with their summer medical care structure (3.3 +/- 1.0) and with the flexibility of summer schedules (3.0 +/- 1.2). Yet the qualitative analysis revealed that perceptions of summer medical care were more positive for shared-care participants than for individual- or combination-care participants. The perceived effect on the athletic trainer included increased workload and expectations and a negative influence on work-life balance, particularly in terms of decreased schedule flexibility and opportunities for rejuvenation. For many, the summer season mimicked the hours, workload, and expectations of the nontraditional season. CONCLUSIONS: The NCAA rule changes and medical care expectations affected the summer workload of athletic trainers, but job sharing seemed to help them manage conflict associated with providing summer athletic training services. PMID- 26881870 TI - Examining Ankle-Joint Laxity Using 2 Knee Positions and With Simulated Muscle Guarding. AB - CONTEXT: Several factors affect the reliability of the anterior drawer and talar tilt tests, including the individual clinician's experience and skill, ankle and knee positioning, and muscle guarding. OBJECTIVES: To compare gastrocnemius activity during the measurement of ankle-complex motion at different knee positions, and secondarily, to compare ankle-complex motion during a simulated trial of muscle guarding. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty-three participants aged 20.2 +/- 1.7 years were tested. INTERVENTION(S): The ankle was loaded under 2 test conditions (relaxed, simulated muscle guarding) at 2 knee positions (0 degrees , 90 degrees of flexion) while gastrocnemius electromyography (EMG) activity was recorded. MAIN OUTCOME MEASURE(S): Anterior displacement (mm), inversion-eversion motion ( degrees ), and peak EMG amplitude values of the gastrocnemius (MUV). RESULTS: Anterior displacement did not differ between the positions of 0 degrees and 90 degrees of knee flexion (P = .193). Inversion-eversion motion was greater at 0 degrees of knee flexion compared with 90 degrees (P < .001). Additionally, peak EMG amplitude of the gastrocnemius was not different between 0 degrees and 90 degrees of knee flexion during anterior displacement (P = .101). As expected, the simulated muscle-guarding trial reduced anterior displacement compared with the relaxed condition (0 degrees of knee flexion, P = .008; 90 degrees of knee flexion, P = .016) and reduced inversion-eversion motion (0 degrees of knee flexion, P = .03; 90 degrees of knee flexion, P < .001). CONCLUSIONS: In a relaxed state, the gastrocnemius muscle did not appear to affect anterior ankle laxity at the 2 most common knee positions for anterior drawer testing; however, talar tilt testing may be best performed with the knee in 0 degrees of knee flexion. Finally, our outcomes from the simulated muscle-guarding condition suggest that clinicians should use caution and be aware of reduced perceived laxity when performing these clinical examination techniques immediately postinjury. PMID- 26881871 TI - Physiological profile of a professional boxer preparing for Title Bout: A case study. AB - This study aimed to (1) profile a professional boxer (23 years and 80 kg) with boxing-specific, muscle function, aerobic capacity and body composition tests, and (2) quantify how these measures varied during an 8-week preparation phase leading to, and post a state-Title Bout fought in the 76.2-kg class. A series of boxing-specific and muscle function tests were completed on 11 occasions: 9 prior and twice after the bout, each separated by approximately 2 weeks. The boxing test included 36 maximal punches (9 of each: lead and rear straights, lead and rear hooks) to a punching integrator measuring forces and velocity. Muscle function tests included countermovement jump, drop-jumps, isometric mid-thigh pull and isometric bench-press. Body composition was assessed using skin-fold measurements on three occasions and one dual energy X-ray absorptiometry scan. Aerobic capacity was assessed using 2 VO2 max tests. Leading up to the bout, performance decreased in isometric mid-thigh pull (8%), isometric bench-press (5%), countermovement jump (15%) and impact forces in 3 of 4 punches (4%-7%). Whereas measures of dynamic and isometric muscle function remained depressed or unchanged post competition, punching forces (6%-15%) and aerobic power (6%) increased. Data suggest the athlete may have super-compensated following rest as fatigue dissipated and further adaptation occurred. PMID- 26881872 TI - Expression of SKA1 and MMP-9 in primary salivary adenoid cystic carcinoma: Correlation with tumor progression and patient prognosis. AB - Conclusion The spindle and kinetochore-associated complex sub unit 1(SKA1) and matrix metalloproteinase-9 (MMP-9) are highly expressed in salivary adenoid cystic carcinoma (SACC), and SKA1 may be the novel, promising prognostic factor for clinical outcomes in head and neck adenoid cystic carcinoma patients. Objectives This study aimed to investigate the expression of SKA1 and MMP-9 in SACC tissues and the clinical significance. Methods SKA1 and MMP-9 expression in samples from 42 cases of SACC and 20 subjects with the normal tissue adjacent to carcinoma were detected by immunohistochemical analysis. Results The positive rate of SKA1 and MMP-9 staining was 78.6% and 66.7% in SACC, respectively, significantly higher than in normal salivary gland tissues (p < 0.001). Chi square test showed that there was no significant correlation between SKA1 expression and MMP-9 expression in SACC tissues. However, SKA1 and MMP-9 expression was positively associated with advanced stage and solid histological pattern of SACC (p < 0.05). In addition, SKA1 and MMP-9 expression was positively associated with recurrence and perineural invasion, and survival time, respectively. PMID- 26881873 TI - [Intraluminal Aspect of Femoro-femoral Cross-over Bypass Graft Mimics Bladder Stone]. AB - Iatrogenic bladder perforation with delayed diagnosis and treatment in the context of the placement of a vascular prosthesis, e.g. a femoro-femoral cross over bypass graft, is extremely rare. This is emphasised by the present publication, which is the second published case study worldwide. To identify such a situation is very important because there is a risk of inappropriate treatment if such a bypass complication remains undetected, and the potential complications of an improperly intended "treatment of a bladder stone" may be deleterious or even lethal. Therefore, the involved disciplines should be aware of this possibility in order to initiate relevant diagnostic measures, especially diagnostic cystoscopy, without any delay if symptoms such as voiding disorders or alguria coincide with vascular bypass grafting. PMID- 26881874 TI - Near-island biological hotspots in barren ocean basins. AB - Phytoplankton production drives marine ecosystem trophic-structure and global fisheries yields. Phytoplankton biomass is particularly influential near coral reef islands and atolls that span the oligotrophic tropical oceans. The paradoxical enhancement in phytoplankton near an island-reef ecosystem--Island Mass Effect (IME)--was first documented 60 years ago, yet much remains unknown about the prevalence and drivers of this ecologically important phenomenon. Here we provide the first basin-scale investigation of IME. We show that IME is a near ubiquitous feature among a majority (91%) of coral reef ecosystems surveyed, creating near-island 'hotspots' of phytoplankton biomass throughout the upper water column. Variations in IME strength are governed by geomorphic type (atoll vs island), bathymetric slope, reef area and local human impacts (for example, human-derived nutrient input). These ocean oases increase nearshore phytoplankton biomass by up to 86% over oceanic conditions, providing basal energetic resources to higher trophic levels that support subsistence-based human populations. PMID- 26881875 TI - Neuropilin-2 promotes melanoma growth and progression in vivo. AB - Tumor cell interactions with their microenvironment, and neighboring endothelial cells in particular, are critical for tumor cell survival and the metastatic process. Within the spectrum of tumors, melanomas are notorious for their ability to metastasize at a relatively early stage of development; however, little is known about the molecular pathways mediating this process. We recently performed a screen to assess critical mediators of melanoma metastasis by evaluating melanoma-endothelial cell communication. Neuropilin-2 (NRP2), a cell surface receptor involved in angiogenesis and axonal guidance, was found to be an important mediator of melanoma-endothelial cell cross-talk in these studies. Here we seek to further define the role of NRP2 in melanoma growth and progression. We use stable gene silencing of NRP2 in melanomas from varying stages of tumor progression to define the role of NRP2 in melanoma growth, migration, invasion, and metastasis. We found that NRP2 gene silencing in metastatic melanoma cell lines inhibited tumor cell growth in vitro; furthermore, knockdown of NRP2 expression in the metastatic melanoma cell line 1205Lu significantly inhibited in vivo tumor growth and metastasis. We conclude that NRP2 plays an important role in mediating melanoma growth and metastasis and suggest that targeting this cell surface molecule may represent a significant therapeutic strategy for patients diagnosed with aggressive forms of melanoma. PMID- 26881876 TI - Ultrasound of the sentinel node in melanoma patients: echo-free island is a discriminatory morphologic feature for node positivity. AB - Unlike breast and thyroid cancer, the use of ultrasound (US)-guided fine needle aspiration cytology (FNAC) for preoperative staging is limited in melanoma. New US morphology criteria have shown that US-FNAC can correctly identify 50% of all involved sentinel nodes (SN) in melanoma patients before surgical excision. The aim of this study was to examine a new criterion: the echo-free island (EFI). A total of 1000 consecutively staged melanoma patients (Breslow thickness>1 or<1 mm, but ulcerated, Clark IV/V or regressed) scheduled for SN staging underwent preoperative US. US morphology items were assessed: peripheral perfusion, loss of central echoes, balloon shape, and EFI. FNAC was performed in case of suspicious and malignant US patterns. All patients proceeded to undergo an SN biopsy or direct completion lymph node dissection (CLND) (in the case of positive FNAC). In all, 57% of the patients were men. The mean/median Breslow thickness was 2.58/1.57 mm. The mean/median follow-up was 56/53 months. SN was positive in 21%. EFI information was available in 95.3%. EFI was seen in 40 patients (4%). EFI sensitivity was 10.8%, specificity was 97.6%, positive predictive value was 50%, and negative predictive value was 80.2%. EFI was significantly correlated to peripheral perfusion (67.5%). There was no correlation to balloon shape or loss of central echoes. Five-year melanoma-specific survival of patients with EFI was significantly worse: 80% versus 92% when absent. The EFI can be useful in the early detection of SN melanoma metastasis. It is an early sign of involvement and thus associated with a decreased survival. PMID- 26881877 TI - Multiple comparisons with two controls for ordered categorical responses. AB - In clinical studies, ordered categorical responses are common. To compare the efficacy of several treatments with a control for ordinal responses, the normal latent variable model has recently been proposed. This approach conceptualizes the responses as manifestations of an underlying continuous normal variable. In this article, we extend this idea to develop the multiple comparison method for use when there are two controls in the clinical trial. The proposed method is constructed such that the familywise type I error rate is controlled at a prespecified level. In addition, for a given level of test power, the procedure to evaluate the required sample size is provided. The proposed testing procedure is also illustrated by an example from a clinical study. PMID- 26881879 TI - Physiotherapy Practice: Opportunities for International Collaboration on Workforce Reforms, Policy and Research. AB - BACKGROUND AND PURPOSE: Physiotherapy or Physical Therapy (PT) is the most commonly practised allied health discipline globally. International PT workforce reforms are underway to deal with increasing patient numbers, shrinking medical and nursing workforces and lengthy waiting lists. It is timely to consider international differences in PT, with the aims of identifying opportunities for shared learning and forming stronger international alliances to support consistent and evidence-based workforce reforms. METHODS: This paper synthesizes freely available information on PT training and service delivery across the UK, Australia and United States (California). The paper considers differences in roles, workplaces, training, legislation and registration, continuing professional development, and accountability. RESULTS: There are similarities between UK, Australia and United States (California) in many areas of PT roles, training, registration, legislation and professional practice. However, none has a standard national mechanism by which to demonstrate PT accountability, patient safety or quality care. Moreover, there are different approaches to workforce reforms. There is considerable duplication in physiotherapy governance. CONCLUSION: There are opportunities for targeted international collaborations regarding workforce reforms such as extending scope of practice, and determining and implementing internationally agreed ways of demonstrating PT accountability. The findings of this review have significant policy implications, and identify areas for collaborative research. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26881878 TI - Anti-norovirus therapeutics: a patent review (2010-2015). AB - INTRODUCTION: Human noroviruses are the primary causative agents of acute gastroenteritis and are a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. An improved understanding of norovirus biology, as well as the pathogenic mechanisms underlying the disease, has provided the impetus for a range of intense exploratory drug discovery efforts targeting viral and host factors. AREAS COVERED: An overview of norovirus inhibitors disclosed in the patent literature (2010-present) and Clinicaltrials.gov is presented. The review is further enriched and supplemented by recent literature reports. EXPERT OPINION: Seminal discoveries made in recent years, including a better understanding of the pathobiology and life cycle of norovirus, the identification and targeting of multiple viral and host factors, the advent of a replicon system and a small animal model for the preclinical evaluation of lead compounds, and the availability of high resolution X-ray crystal structures that can be utilized in structure-based drug design and lead optimization campaigns, collectively suggest that a small molecule therapeutic and prophylactic for norovirus infection is likely to emerge in the not too distant future. PMID- 26881880 TI - Prognostic Value of Protocadherin10 (PCDH10) Methylation in Serum of Prostate Cancer Patients. AB - BACKGROUND Prostate cancer is a heterogeneous malignancy with outcome difficult to predict. Currently, there is an urgent need to identify novel biomarkers that can accurately predict patient outcome and improve the treatment strategy. The aim of this study was to investigate the methylation status of PCDH10 in serum of prostate cancer patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS The methylation status of PCDH10 in serum of 171 primary prostate cancer patients and 65 controls was evaluated by methylation-specific PCR (MSP), after which the relationship between PCDH10 methylation and clinicopathologic features was evaluated. Kaplan-Meier survival analysis and Cox analysis were used to evaluate the correlation between PCDH10 methylation and prognosis. RESULTS PCDH10 methylation occurred frequently in serum of prostate cancer patients. Moreover, PCDH10 methylation was significantly associated with higher preoperative PSA level, advanced clinical stage, higher Gleason score, lymph node metastasis, and biochemical recurrence (BCR). In addition, patients with methylated PCDH10 had shorter BCR-free survival and overall survival than patients with unmethylated PCDH10. Univariate and multivariate Cox proportional hazards model analysis indicated that PCDH10 methylation in serum is an independent predictor of worse BCR-free survival and overall survival. CONCLUSIONS PCDH10 methylation in serum is a potential prognostic biomarker for prostate cancer. PMID- 26881881 TI - Chemoenzymatic synthesis of (S)-duloxetine using carbonyl reductase from Rhodosporidium toruloides. AB - A chemoenzymatic strategy was developed for (S)-duloxetine production employing carbonyl reductases from newly isolated Rhodosporidium toruloides into the enantiodetermining step. Amongst the ten most permissive enzymes identified, cloned, and overexpressed in Escherichia coli, RtSCR9 exhibited excellent activity and enantioselectivity. Using co-expressed E. coli harboring both RtSCR9 and glucose dehydrogenase, (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol 3a was fabricated with so far the highest substrate loading (1000mM) in a space-time yield per gram of biomass (DCW) of 22.9mmolL(-1)h(-1)gDCW(-1) at a 200-g scale. The subsequent synthetic steps from RtSCR9-catalyzed (S)-3a were further performed, affording (S)-duloxetine with 60.2% overall yield from 2 acethylthiophene in >98.5% ee. PMID- 26881882 TI - Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells. AB - BACKGROUND: Recent studies have shown that heterogeneous nuclear ribonucleoprotein U (hnRNP U), a component of the hnRNP complex, contributes to stabilize the kinetochore-microtubule interaction during mitosis. CENP-W was identified as an inner centromere component that plays crucial roles in the formation of a functional kinetochore complex. RESULTS: We report that hnRNP U interacts with CENP-W, and the interaction between hnRNP U and CENP-W mutually increased each other's protein stability by inhibiting the proteasome-mediated degradation. Further, their co-localization was observed chiefly in the nuclear matrix region and at the microtubule-kinetochore interface during interphase and mitosis, respectively. Both microtubule-stabilizing and microtubule-destabilizing agents significantly decreased the protein stability of CENP-W. Furthermore, loss of microtubules and defects in microtubule organization were observed in CENP-W depleted cells. CONCLUSION: Our data imply that CENP-W plays an important role in the attachment and interaction between microtubules and kinetochore during mitosis. PMID- 26881883 TI - Activation energy associated with the electromigration of oligosaccharides through viscosity modifier and polymeric additive containing background electrolytes. AB - The activation energy related to the electromigration of oligosaccharides can be determined from their measured electrophoretic mobilities at different temperatures. The effects of a viscosity modifier (ethylene glycol) and a polymeric additive (linear polyacrylamide) on the electrophoretic mobility of linear sugar oligomers with alpha1-4 linked glucose units (maltooligosaccharides) were studied in CE using the activation energy concept. The electrophoretic separations of 8-aminopyrene-1,3,6-trisulfonate-labeled maltooligosaccharides were monitored by LIF detection in the temperature range of 20-50 degrees C, using either 0-60% ethylene glycol (viscosity modifier) or 0-3% linear polyacrylamide (polymeric additive) containing BGEs. Activation energy curves were constructed based on the slopes of the Arrhenius plots. With the use of linear polyacrylamide additive, solute size-dependent activation energy variations were found for the maltooligosaccharides with polymerization degrees below and above maltoheptaose (DP 7), probably due to molecular conformation changes and possible matrix interaction effects. PMID- 26881889 TI - Applying the Principles of McDonaldization to Medicine--Reply. PMID- 26881888 TI - MRSA: treating people with infection. AB - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has a gene that makes it resistant to methicillin, as well as to other beta-lactam antibiotics, including flucloxacillin, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, and carbapenems. MRSA can be part of the normal body flora (colonisation), especially in the nose, but it can cause infection, particularly in people with prolonged hospital admissions, with underlying disease, or after antibiotic use. About 8% of S aureus in blood cultures in England, Wales, and Northern Ireland is resistant to methicillin. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of selected treatments for MRSA infections at any body site? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 312 studies. After deduplication and removal of conference abstracts, 133 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 55 studies and the further review of 78 full publications. Of the 78 full articles evaluated, 15 systematic reviews and one subsequent RCT were added at this update. In addition, six studies were added to the Comment sections. We performed a GRADE evaluation for 12 PICO combinations. CONCLUSIONS: In this systematic overview we categorised the efficacy for five interventions, based on information about the effectiveness and safety of cephalosporins (ceftobiprole, ceftaroline), daptomycin, linezolid, quinupristin-dalfopristin, pristinamycin (streptogramins), and tigecycline. PMID- 26881890 TI - Repair of a Defect of the Lateral Suprabow. PMID- 26881891 TI - The Twenty-Year Trajectory of Suicidal Activity Among Post-Hospital Psychiatric Men and Women with Mood Disorders and Schizophrenia. AB - The Chicago Follow-up Study has followed the course of severe mental illness among psychiatric patients for more than 20 years after their index hospitalization. Among these patients are 97 schizophrenia patients, 45 patients with schizoaffective disorders, 102 patients with unipolar nonpsychotic depression, and 53 patients with a bipolar disorder. Maximum suicidal activity (suicidal ideation, suicidal attempts and suicide completions) generally declines over the 3 time periods (early, middle, and late follow-ups) following discharge from the acute psychiatric hospitalization for both males and females across diagnostic categories with two exceptions: female schizophrenia patients and female bipolar patients. A weighted mean suicidal activity score tended to decrease across follow-ups for male patients in the schizophrenia, schizoaffective, and depressive diagnostic groups with an uneven trend in this direction for the male bipolars. No such pattern emerges for our female patients except for female depressives. Males' suicidal activity seems more triggered by psychotic symptoms and potential chronic disability while females' suicidal activity seems more triggered by affective symptoms. PMID- 26881892 TI - A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks. AB - Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications. PMID- 26881893 TI - Continuous Improvement of Physical Functioning in Ankylosing Spondylitis Patients by Tumor Necrosis Factor Inhibitors: Three-Year Followup and Predictors. AB - OBJECTIVE: To establish the 3-year outcome and course of physical functioning and spinal mobility impairments in patients routinely treated with tumor necrosis factor inhibitors (TNFi) and to find predictors of physical functioning and spinal mobility impairments. METHODS: Ankylosing spondylitis (AS) patients eligible for TNFi were followed in a 3-year prospective observational study. Prediction models were developed with linear mixed modeling. Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) were used as outcome measures for physical functioning and spinal mobility. RESULTS: A total of 257 patients were included and treated with etanercept (n = 174) or adalimumab (n = 83). Physical functioning improved significantly during the first 6 months after the start of TNFi. The BASFI score decreased from mean +/- SD 5.4 +/- 2.4 to 3.3 +/- 2.6 at 6 months, and stabilized thereafter (BASFI third year score mean +/- SD 3.6 +/- 2.5). The BASMI showed no significant changes over time. Lower baseline BASFI and BASMI scores predicted a better level of physical functioning and spinal mobility after 3 years of TNFi therapy. Other predictors for a better 3-year outcome and course of physical functioning included absence of comorbidity, physical activity, younger age, and lower body mass index at baseline. CONCLUSION: Physical functioning in routinely TNFi-treated AS patients improved up to 6 months and stabilized thereafter. Therefore, it would be better to extend the period of evaluation of TNFi treatment to 6 months rather than the 3 months currently used. The risk factors of long-term physical functioning found in this study might help to identify patients at risk at an earlier stage and improve treatment strategy. PMID- 26881894 TI - Linking Genetic Variation in Adaptive Plant Traits to Climate in Tetraploid and Octoploid Basin Wildrye [Leymus cinereus (Scribn. & Merr.) A. Love] in the Western U.S. AB - Few studies have assessed how ploidy type within a species affects genetic variation among populations in relation to source climates. Basin wildrye (Leymus cinereus (Scribn. & Merr.) A. Love) is a large bunchgrass common in the intermountain Western U.S. found in both octoploid and tetraploid types. In common gardens at two sites over two years differences in both ploidy type and genetic variation within ploidy were observed in phenology, morphology, and production traits on 57 octoploid and 52 tetraploid basin wildrye from the intermountain Western U.S. (P<0.01). Octoploids had larger leaves, longer culms, and greater crown circumference than tetraploids but the numerical ranges of plant traits and their source climates overlapped between ploidy types. Still, among populations octoploids often had greater genetic variation for traits and occupied more diverse climates than tetraploids. Genetic variation for both ploidy types was linked to source climates in canonical correlation analysis, with the first two variates explaining 70% of the variation. Regression of those canonical variates with seed source climate variables produced models that explained 64% and 38% of the variation, respectively, and were used to map 15 seed zones covering 673,258 km2. Utilization of these seed zones will help ensure restoration with adaptive seed sources for both ploidy types. The link between genetic traits and seed source climates suggests climate driven natural selection and adaptive evolution in basin wildrye. The more diverse climates occupied by octoploids and higher trait variation suggests a higher capacity for ecological differentiation than tetraploids in the intermountain Western U.S. PMID- 26881895 TI - Improved Endurance and Resistive Switching Stability in Ceria Thin Films Due to Charge Transfer Ability of Al Dopant. AB - An improvement in resistive switching (RS) characteristics of CeO2-based devices has been reported by charge transfer through Al metal as a dopant. Moreover, density functional theory (DFT) calculations have been performed to investigate the role of Al-layer sandwiched between CeO2 layers by the Vienna ab initio simulation package (VASP). Total density of states (TDOS) and partial electron density of states (PDOS) have been calculated and analyzed with respect to resistive switching. It is established that the oxygen vacancy based conductive filaments are formed and ruptured in the upper region of CeO2 layer, because of the fact that maximum transport of charge takes place in this region by Al and Ti (top electrode), while the lower region revealed less capability to generate conductive filaments because minimum charge transfer takes place in this region by Al and/or Pt (bottom electrode). The effect of Al and Al2O3 on both the electronic charge transfer from valence to conduction bands and the formation stability of oxygen vacancies in conductive filament have been discussed in detail. Experimental results demonstrated that the Ti/CeO2:Al/Pt sandwich structure exhibits significantly better switching characteristics including lower forming voltage, improved and stable SET/RESET voltages, enhanced endurance of more than 10(4) repetitive switching cycles and large memory window (ROFF/RON > 10(2)) as compared to undoped Ti/CeOx/Pt device. This improvement in memory switching behavior has been attributed to a significant decrease in the formation energy of oxygen vacancies and to the enhanced oxygen vacancies generation within the CeO2 layers owing to charge transferring and oxygen gettering ability of Al dopant. PMID- 26881896 TI - How work-self conflict/facilitation influences exhaustion and task performance: A three-wave study on the role of personal resources. AB - Although work and family are undoubtedly important life domains, individuals are also active in other life roles which are also important to them (like pursuing personal interests). Building on identity theory and the resource perspective on work-home interface, we examined whether there is an indirect effect of work-self conflict/facilitation on exhaustion and task performance over time through personal resources (i.e., self-efficacy and optimism). The sample was composed of 368 Dutch police officers. Results of the 3-wave longitudinal study confirmed that work-self conflict was related to lower levels of self-efficacy, whereas work-self facilitation was related to improved optimism over time. In turn, self efficacy was related to higher task performance, whereas optimism was related to diminished levels of exhaustion over time. Further analysis supported the negative, indirect effect of work-self facilitation on exhaustion through optimism over time, and only a few reversed causal effects emerged. The study contributes to the literature on interrole management by showing the role of personal resources in the process of conflict or facilitation over time. (PsycINFO Database Record PMID- 26881898 TI - Learning about the CS during latent inhibition: Preexposure enhances temporal control. AB - In 3 experiments, rats were given nonreinforced preexposure to an auditory stimulus, after which this stimulus and a second, novel cue were paired with food. Lower rates of conditioned responding were observed to the preexposed stimulus across the 3 experiments, indicative of latent inhibition. The degree to which animals used these cues to time the occurrence of food delivery was also examined. Paradoxically, the response slopes-indicating the rate of increase in responding over the course of the conditioned stimulus-were greater for the preexposed than for the novel cues, consistent with the suggestion that the preexposed stimulus exerted greater temporal control. Moreover, this was the case irrespective of whether the duration of the cue during preexposure differed from that during conditioning. These results suggest that although conditioned stimulus preexposure retards conditioning, it may enhance timing. The findings are discussed in terms of current models of conditioning and timing. PMID- 26881897 TI - Effects of Nonpurified and Choline Supplemented or Nonsupplemented Purified Diets on Hepatic Steatosis and Methionine Metabolism in C3H Mice. AB - BACKGROUND: Previous studies indicated that nonpurified and purified commercially available control murine diets have different metabolic effects with potential consequences on hepatic methionine metabolism and liver histology. METHODS: We compared the metabolic and histological effects of commercial nonpurified (13% calories from fat; 57% calories from carbohydrates with 38 grams/kg of sucrose) and purified control diets (12% calories from fat; 69% calories from carbohydrates with ~500 grams/kg of sucrose) with or without choline supplementation administered to C3H mice with normal lipid and methionine metabolism. Diets were started 2 weeks before mating, continued through pregnancy and lactation, and continued in offspring until 24 weeks of age when we collected plasma and liver tissue to study methionine and lipid metabolism. RESULTS: Compared to mice fed nonpurified diets, the liver/body weight ratio was significantly higher in mice fed either purified diet, which was associated with hepatic steatosis and inflammation. Plasma alanine aminotransferase levels were higher in mice receiving the purified diets. The hepatic S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio was higher in female mice fed purified compared to nonpurified diet (4.6 +/- 2 vs. 2.8 +/- 1.9; P < 0.05). Choline supplementation was associated with improvement of some parameters of lipid and methionine metabolism in mice fed purified diets. CONCLUSIONS: Standard nonpurified and purified diets have significantly different effects on development of steatosis in control mice. These findings can help in development of animal models of fatty liver and in choosing appropriate laboratory control diets for control animals. PMID- 26881900 TI - Imagine that! Cue-evoked representations guide rat behavior during ambiguous situations. AB - Mental imagery involves the perceptual-like experience of an event that is not physically present, or detected by the senses. Fast and Blaisdell (2011) reported that rats use the representation of an associatively retrieved event to guide behavior in ambiguous situations. Rats were reinforced for lever-pressing during 1 of 2 lights but not both lights. They were then tested with 1 light illuminated while the second light was either covered by an opaque shield (ambiguous) or uncovered and unlit (explicitly absent). Rats lever-pressed less when the second light was covered compared with unlit, suggesting that a representation of the ambiguously absent light guided their behavior. However, Dwyer and Burgess (2011) offered an alternative mechanism in which the explicit absence of a cue gains associative value during training. Covering the light at test could effectively remove these associative properties, resulting in a generalization decrement of behavior. The current experiments were designed to test contrasting predictions made by these 2 accounts. Experiment 1 empirically established that generalization decrement can occur when an element of a compound cue is presented alone at test, but this decrement is attenuated, rather than enhanced, when the absent element is covered. Experiment 2 utilized a conditioned inhibition procedure to demonstrate that rat behavior during cue ambiguity is driven by an associatively retrieved representation rather than by generalization decrement. Collectively, the results argue against a purely nonrepresentational associative account of behavior and support a role for associatively retrieved representations in rats. PMID- 26881901 TI - The effect of additional exposure to the unique features in a perceptual learning task can be attributed to a location bias. AB - It has been suggested that human perceptual learning could be explained in terms of a better memory encoding of the unique features during intermixed exposure. However, it is possible that a location bias could play a relevant role in explaining previous results of perceptual learning studies using complex visual stimuli. If this were the case, the only relevant feature would be the location, rather than the content, of the unique features. To further explore this possibility, we attempted to replicate the results of Lavis, Kadib, Mitchell, and Hall (2011, Experiment 2), which showed that additional exposure to the unique elements resulted in better discrimination than simple intermixed exposure. We manipulated the location of the unique elements during the additional exposure. In one experiment, they were located in the same position as that when presented together with the common element. In another experiment, the unique elements were located in the center of the screen, regardless of where they were located together with the common element. Our results showed that additional exposure only improved discrimination when the unique elements were presented in the same position as when they were presented together with the common element. The results reported here do not provide support for the explanation of the effects of additional exposure of the unique elements in terms of a better memory encoding and instead suggest an explanation in terms of location bias. PMID- 26881899 TI - Delay discounting: Pigeon, rat, human--does it matter? AB - Delay discounting refers to the decrease in subjective value of an outcome as the time to its receipt increases. Across species and situations, animals discount delayed rewards, and their discounting is well-described by a hyperboloid function. The current review begins with a comparison of discounting models and the procedures used to assess delay discounting in nonhuman animals. We next discuss the generality of discounting, reviewing the effects of different variables on the degree of discounting delayed reinforcers by nonhuman animals. Despite the many similarities in discounting observed between human and nonhuman animals, several differences have been proposed (e.g., the magnitude effect; nonhuman animals discount over a matter of seconds whereas humans report willing to wait months, if not years before receiving a reward), raising the possibility of fundamental species differences in intertemporal choice. After evaluating these differences, we discuss delay discounting from an adaptationist perspective. The pervasiveness of discounting across species and situations suggests it is a fundamental process underlying decision making. PMID- 26881902 TI - Suboptimal choice in pigeons: Choice is primarily based on the value of the conditioned reinforcer rather than overall reinforcement rate. AB - Pigeons have sometimes shown a preference for a signaled 50% reinforcement alternative (leading half of the time to a stimulus that signaled 100% reinforcement and otherwise to a stimulus that signaled 0% reinforcement) over a 100% reinforcement alternative. We hypothesized that pigeons may actually be indifferent between the 2 alternatives with previous inconsistent preferences resulting in part from an artifact of the use of a spatial discrimination. In the present experiments, we tested the hypothesis that pigeons would be indifferent between alternatives that provide conditioned reinforcers of equal value. In Experiment 1, we used the signaled 50% reinforcement versus 100% reinforcement procedure, but cued the alternatives with shapes that varied in their spatial location from trial to trial. Consistent with the stimulus value hypothesis, the pigeons showed indifference between the alternatives. In Experiment 2, to confirm that the pigeons could discriminate between the shapes, we removed the discriminative function from the 50% reinforcement alternative and found a clear preference for the 100% reinforcement alternative. Finally, in Experiment 3, when we returned the discriminative function to the 50% reinforcement alternative and reduced the 100% reinforcement alternative to 50% reinforcement, we found a clear preference for the discriminative stimulus alternative. These results support the hypothesis that pigeons prefer the alternative with the conditioned reinforcer that best predicts reinforcement, whereas its frequency may be relatively unimportant. PMID- 26881903 TI - Complexes with Tunable Intramolecular Ferrocene to Ti(IV) Electronic Transitions: Models for Solid State Fe(II) to Ti(IV) Charge Transfer. AB - Iron(II)-to-titanium(IV) metal-to-metal-charge transfer (MMCT) is important in the photosensitization of TiO2 by ferrocyanide, charge transfer in solid-state metal-oxide photocatalysts, and has been invoked to explain the blue color of sapphire, blue kyanite, and some lunar material. Herein, a series of complexes with alkynyl linkages between ferrocene (Fc) and Ti(IV) has been prepared and characterized by UV-vis spectroscopy and electrochemistry. Complexes with two ferrocene substituents include Cp2Ti(C2Fc)2, Cp*2Ti(C2Fc)2, and Cp2Ti(C4Fc)2. Complexes with a single ferrocene utilize a titanocene with a trimethylsilyl derivatized Cp ring, (TMS)Cp, and comprise the complexes (TMS)Cp2Ti(C2Fc)(C2R), where R = C6H5, p-C6H4CF3, and CF3. The complexes are compared to Cp2Ti(C2Ph)2, which lacks the second metal. Cyclic voltammetry for all complexes reveals a reversible Ti(IV/III) reduction wave and an Fe(II/III) oxidation that is irreversible for all complexes except (TMS)Cp2Ti(C2Fc)(C2CF3). All of the complexes with both Fc and Ti show an intense absorption (4000 M(-1)cm(-1) < epsilon < 8000 M(-1)cm(-1)) between 540 and 630 nm that is absent in complexes lacking a ferrocene donor. The energy of the absorption tracks with the difference between the Ti(IV/III) and Fe(III/II) reduction potentials, shifting to lower energy as the difference in potentials decreases. Reorganization energies, lambda, have been determined using band shape analysis (2600 cm(-1) < lambda < 5300 cm(-1)) and are in the range observed for other donor-acceptor complexes that have a ferrocene donor. Marcus-Hush-type analysis of the electrochemical and spectroscopic data are consistent with the assignment of the low-energy absorption as a MMCT band. TD-DFT analysis also supports this assignment. Solvatochromism is apparent for the MMCT band of all complexes, there being a bathochromic shift upon increasing polarizability of the solvent. The magnitude of the shift is dependent on both the electron density at Ti(IV) and the identity of the linker between the titanocene and the Fc. Complexes with a MMCT are photochemically stable, whereas Cp2Ti(C2Ph)2 rapidly decomposes upon photolysis. PMID- 26881905 TI - Pressure-induced phase transition in Bi2Se3 at 3 GPa: electronic topological transition or not? AB - In recent years, a low pressure transition around P3 GPa exhibited by the A2B3 type 3D topological insulators is attributed to an electronic topological transition (ETT) for which there is no direct evidence either from theory or experiments. We address this phase transition and other transitions at higher pressure in bismuth selenide (Bi2Se3) using Raman spectroscopy at pressure up to 26.2 GPa. We see clear Raman signatures of an isostructural phase transition at P2.4 GPa followed by structural transitions at ~ 10 GPa and 16 GPa. First principles calculations reveal anomalously sharp changes in the structural parameters like the internal angle of the rhombohedral unit cell with a minimum in the c/a ratio near P3 GPa. While our calculations reveal the associated anomalies in vibrational frequencies and electronic bandgap, the calculated Z2 invariant and Dirac conical surface electronic structure remain unchanged, showing that there is no change in the electronic topology at the lowest pressure transition. PMID- 26881904 TI - Pulmonary resident neutrophils regulate the production of GM-CSF and alveolar macrophages. AB - Alveolar macrophages exist in the lung airspaces, and their differentiation and function are considerably regulated by the microenvironment. In this study, we examine the important role of resident neutrophil/IL-23/granulocyte/macrophage colony-stimulating factor (GM-CSF) axis in the development and preferential phenotype of alveolar macrophages under physiological conditions. Using CD18 deficient (CD18(-/-) ) mice, we show a correlation between increased granulopoiesis and enhanced alveolar macrophage development in an IL-23- and GM CSF-dependent manner. The apoptotic neutrophils could inhibit the secretion of IL 23 from alveolar macrophages, which is important for the production of GM-CSF, and depletion of neutrophils disrupted the regulation of IL-23 and GM-CSF. This study reveals a mechanism for the regulation of the local alveolar macrophage population and function by neutrophil apoptosis in the circulatory system. PMID- 26881906 TI - Synthesis and characterization of a highly strained donor-acceptor nanohoop. AB - A highly-strained, nitrogen-doped cycloparaphenylene (CPP), aza[6]CPP, was synthesized and then converted to a donor-acceptor nanohoop, N-methylaza[6]CPP, via alkylation of the nitrogen center. The energy levels of the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO) for both molecules were then probed by cyclic voltammetry (CV), which revealed that the donor-acceptor nanohoop had a significantly lower LUMO energy relative to [6]CPP and aza[6]CPP. Density functional theory (DFT) revealed that the donor acceptor nanohoop underwent a redistribution of the frontier molecular orbital (FMO) density such that a significant portion of the LUMO density resided upon the electron-deficient nitrogen-containing ring. This localization of LUMO density caused a large lowering in the LUMO energy of nearly a full electron volt, while the HOMO energy was less affected due to a large centralization of the FMO on the electron-rich phenylene backbone. This ultimately resulted in a net lowering of the HOMO-LUMO energy gap which was observed both experimentally and computationally. In addition, N-methylaza[6]CPP has a significantly lower energy LUMO than N-methylaza[8]CPP, illustrating that the FMO levels of donor acceptor nanohoops can be tuned by adjusting the hoop size. PMID- 26881907 TI - Experimental Droplet Study of Inverted Marangoni Effect of a Binary Liquid Mixture on a Nonuniform Heated Substrate. AB - We present an experimental study on the inversion of the Marangoni effect of a binary mixture droplet under a horizontal temperature gradient. In particular, we studied the dynamics and the evaporation behavior under these conditions. We show that a binary mixture (97% water-3% butanol) droplet has a tendency to migrate to warmer areas, as opposed to spreading in pure fluids. During the evaporation process, we distinguish three stages of evaporation that are correlated to the dynamics of the droplet. PMID- 26881908 TI - De Novo Design at the Edge of Chaos. AB - Computational medicinal chemistry offers viable strategies for finding, characterizing, and optimizing innovative pharmacologically active compounds. Technological advances in both computer hardware and software as well as biological chemistry have enabled a renaissance of computer-assisted "de novo" design of molecules with desired pharmacological properties. Here, we present our current perspective on the concept of automated molecule generation by highlighting chemocentric methods that may capture druglike chemical space, consider ligand promiscuity for hit and lead finding, and provide fresh ideas for the rational design of customized screening of compound libraries. PMID- 26881909 TI - Pd(II)-Catalyzed Aminofluorination of Alkenes in Total Synthesis 6-(R) Fluoroswainsonine and 5-(R)-Fluorofebrifugine. AB - The total syntheses of two fluorinated alkaloids, 6-(R)-fluoroswainsonine and 5 (R)-fluorofebrifugine, are described. Both encompass (4aS,7R,8aR)-7-fluoro-5 tosylhexahydro-4H-[1,3]dioxino[5,4-b]pyridine as a key synthon which is obtained through a further optimized palladium-catalyzed aminofluorination of alkenes with high diastereoselectivity. 6-(R)-Fluoroswainsonine is synthesized from the key synthon in 14 steps, and 5-(R)-fluorofebrifugine requires a sequential 15-step transformation. PMID- 26881910 TI - One size fits all? Determinants of sperm transfer in a highly dimorphic orb-web spider. AB - The evolutionary significance of widespread hypo-allometric scaling of genital traits in combination with rapid interspecific genital trait divergence has been of key interest to evolutionary biologists for many years and remains poorly understood. Here, we provide a detailed assessment of quantitative genital trait variation in males and females of the sexually highly dimorphic and cannibalistic orb-weaving spider Argiope aurantia. We then test how this trait variation relates to sperm transfer success. In particular, we test specific predictions of the one-size-fits-all and lock-and-key hypotheses for the evolution of genital characters. We use video-taped staged matings in a controlled environment with subsequent morphological microdissections and sperm count analyses. We find little support for the prediction of the one-size-fits-all hypothesis for the evolution of hypo-allometric scaling of genital traits, namely that intermediate trait dimensions confer highest sperm transfer success. Likewise, our findings do not support the prediction of the lock-and-key hypothesis that a tight fit of male and female genital traits mediates highest sperm transfer success. We do, however, detect directional effects of a number of male and female genital characters on sperm transfer, suggesting that genital trait dimensions are commonly under selection in nature. Importantly, even though females are much larger than males, spermatheca size limits the number of sperm transferred, contradicting a previous hypothesis about the evolutionary consequences of genital size dimorphism in extremely size-dimorphic taxa. We also find strong positive effects of male body size and copulation duration on the probability of sperm transfer and the number of sperm transferred, with implications for the evolution of extreme sexual size dimorphism and sexual cannibalism in orb weavers. PMID- 26881911 TI - Transbronchial Lung Cryobiopsy: New Options for a New Reality. PMID- 26881913 TI - Oral tofacitinib for the treatment of adults with moderate to severe chronic plaque psoriasis. AB - New treatments for psoriasis have been developed based on increasing knowledge of the underlying pathogenesis of the disease. The development of very safe and highly effective biologics has revolutionized the treatment of moderate-to-severe psoriasis. Biologics are not perfect, however, as they are delivered parenterally, immunogenic, and costly. Small molecule agents, with molecular weights of less than 1 kDa, are being developed and hold the advantage of being administered orally. Tofacitinib is an oral Janus kinase inhibitor that has been developed to disrupt the aberrant JAK-STAT pathway that contributes to the pathogenesis of psoriasis. Phase II and Phase III clinical trial results for tofacitinib are encouraging, demonstrating substantial efficacy and satisfactory safety in the treatment of patients with moderate-to-severe chronic plaque psoriasis. An effective oral treatment without the organ toxicities of methotrexate and cyclosporine, tofacitinib is a promising alternative to biologics in the treatment of moderate-to-severe psoriasis. PMID- 26881912 TI - Husbandry and propagation of the Chinese big-headed turtle (Platysternon megacephalum) at the Wildlife Conservation Society's Prospect Park Zoo. AB - Turtles worldwide are facing increasing pressures on their wild populations and many are listed as endangered or critically endangered. Chinese big-headed turtles (Platysternon megacephalum) are currently listed on IUCN's Red List as endangered and on Cites Appendix II. As part of the Wildlife Conservation Society's initiative on turtle and tortoise conservation, this species became a focus for propagation at Prospect Park Zoo (PPZ) in 2008. PPZ successfully bred and obtained eggs, with successful hatchings in 2013 and 2014. The staff fluctuated water and ambient temperatures along with photoperiod in order to simulate seasonal changes. Each May, the female was placed in the male's enclosure daily for at least 15 min for breeding. Once two confirmed copulations were observed, breeding introductions were discontinued. The female laid her eggs in July and August, and clutch sizes ranged from 5 to 6 eggs. Eggs were successfully incubated in a RCOM Juragon reptile incubator at 23.3 degrees C with 90-95% humidity. The eggs hatched after an average incubation period of 102 days (98-105 days, n = 9). Hatchlings had a mean body mass of 8.84 g (8.11-10 g) and average carapace length * width of 36.17 * 32.20 mm. This article aims to share the team's experiences working with this species as well as build upon previous publications and successes. Our hope is that with continued efforts to increase our knowledgebase a future viable, sustainable North American captive population will become a reality for this species. PMID- 26881914 TI - Biomarkers for Diagnosis, Prognosis and Intervention in Acute Kidney Injury. AB - Biomarkers for acute kidney injury (AKI) can be used for diagnosis and prognosis and to guide therapy. With no pharmacologic therapy clinically available for the treatment of AKI, prevention and early detection are of paramount importance. Despite the initial enthusiasm for biomarker use when it was first introduced in the literature, published studies' results have shown variability in biomarker performance. The following chapter will discuss what our expectations of AKI biomarkers should be and how they can be currently used for a variety of clinical purposes. PMID- 26881915 TI - Patient and Public Risks of Powdered Alcohol: A Citywide Case Study to Prevent Abuse. PMID- 26881916 TI - Tebuthiuron Movement via Leaching and Runoff from Grazed Vertisol and Alfisol Soils in the Brigalow Belt Bioregion of Central Queensland, Australia. AB - Tebuthiuron is one of five priority herbicides identified as a water pollutant entering the Great Barrier Reef. A review of tebuthiuron research in Australia found 13 papers, 6 of which focused on water quality at the basin scale (>10,000 km(2)) with little focus on process understanding. This study examined the movement of tebuthiuron in soil and runoff at the plot (1.7 m(2)) and small catchment (12.7 ha) scales. The greatest concentration and mass in soil occurred from 0 to 0.05 m depth 30-57 days after application. Concentrations at all depths tended to decrease after 55-104 days. Runoff at the small catchment scale contained high concentrations of tebuthiuron (average = 103 MUg/L) 100 days after application, being 0.05% of the amount applied. Tebuthiuron concentrations in runoff declined over time with the majority of the chemical in the dissolved phase. PMID- 26881917 TI - Gouty Arthritis of the Atlantodental Joint. PMID- 26881918 TI - Analysis of Plasma Cytokine and Chemokine Profiles in Patients with and without Tuberculosis by Liquid Array-Based Multiplexed Immunoassays. AB - The aim of this study was to establish plasma cytokine/chemokine profiles in patients with 3 different presentations of active tuberculosis (TB), compared to the profiles observed in bacillus Calmette-Guerin (BCG)-vaccinated healthy individuals and patients with other pulmonary diseases (non-TB patients). To this end, plasma samples were collected from 151 TB patients including 68 pulmonary TB (PTB), 43 endobronchial TB, and 40 tuberculosis pleurisy (TP) patients, as well as 107 no-TB cases including 26 non-TB patients and 81 BCG-vaccinated healthy controls. A liquid array-based multiplexed immunoassay was used to screen plasma samples for 20 distinct cytokines and chemokines. Multinomial logistic regression was used to analyze associations between cytokines/chemokines and TB/non-TB patients. Compared to our findings with the no-TB donors, the median plasma levels of the proinflammatory cytokines/chemokines TNF-alpha, IL-6, IP-10, IFN gamma, and MIP-1beta were significantly elevated in TB patients, suggesting their potential use as biomarkers for diagnosing TB patients. Further comparisons with healthy donors showed that only the median TNF-alpha plasma level was highly produced in the plasma of all 3 types of TB patients. Plasma IL-6 production was higher only in TP patients, while the plasma levels of IP-10, IFN-gamma, and MIP 1beta were markedly enhanced in both PTB and TP patients. Unexpectedly, among the above cytokines/chemokines, MIP-1beta was also highly expressed in non-TB patients, compared with healthy donors. Our results suggested that TNF-alpha may be an ideal biomarker for diagnosing the 3 forms of TB presentation, while the other factors (IL-6, IP-10, MCP-1, and IFN-gamma) can potentially facilitate differential diagnosis for the 3 TB presentation types. Further characterization of immune responses associated with different types of TB diseases will provide a basis for developing novel TB diagnostics. PMID- 26881919 TI - The incidence of osteoarthritic change on computed tomography of Korean temporomandibular disorder patients diagnosed by RDC/TMD; a retrospective study. AB - Objective Osteoarthritis (OA) of the temporomandibular joint (TMJ) is generally thought to be an age-related disease like those of other joints. This study aims to investigate the incidence of computed tomographic (CT) OA changes in Korean temporomandibular disorder (TMD) patients diagnosed by the Research Diagnostic Criteria for TMD (RDC/TMD). Materials and methods The clinical records and radiographs of 1038 TMD patients (297 men and 741 women with mean age 31.1 +/- 17.4 and 34.0 +/- 16.2, respectively) diagnosed based on RDC/TMD Axis I in 2010 were reviewed. Results The incidence rate of OA changes in TMD patients is estimated to 27.3%, and higher in women than in men (15.5% in men and 32.0% in women) by 2.3 odds (p < 0.001). It has no correlation with age, showing an almost flat incidence rate throughout the age from the 2nd decade and has no correlation as well with pain or disc displacement diagnosed according to RDC/TMD, while arthrosis/arthritis diagnosis based on RDC/TMD supplemented by plain radiographs shows high risk of OA changes on CT by 38.8 odds (p < 0.05). Conclusions These results imply that the OA changes in young Korean TMD patients are as common as in the old and have no correlation with clinical pain and noise. Considered with high prevalence of TMDs known in the young population, the overall/absolute OA changes in the TMJ can be even higher in the young than in the old population, not like in other joints. PMID- 26881920 TI - Effects of Uniaxial and Biaxial Strain on Few-Layered Terrace Structures of MoS2 Grown by Vapor Transport. AB - One of the most fascinating properties of molybdenum disulfide (MoS2) is its ability to be subjected to large amounts of strain without experiencing degradation. The potential of MoS2 mono- and few-layers in electronics, optoelectronics, and flexible devices requires the fundamental understanding of their properties as a function of strain. While previous reports have studied mechanically exfoliated flakes, tensile strain experiments on chemical vapor deposition (CVD)-grown few-layered MoS2 have not been examined hitherto, although CVD is a state of the art synthesis technique with clear potential for scale-up processes. In this report, we used CVD-grown terrace MoS2 layers to study how the number and size of the layers affected the physical properties under uniaxial and biaxial tensile strain. Interestingly, we observed significant shifts in both the Raman in-plane mode (as high as -5.2 cm(-1)) and photoluminescence (PL) energy (as high as -88 meV) for the few-layered MoS2 under ~1.5% applied uniaxial tensile strain when compared to monolayers and few-layers of MoS2 studied previously. We also observed slippage between the layers which resulted in a hysteresis of the Raman and PL spectra during further applications of strain. Through DFT calculations, we contended that this random layer slippage was due to defects present in CVD-grown materials. This work demonstrates that CVD-grown few layered MoS2 is a realistic, exciting material for tuning its properties under tensile strain. PMID- 26881921 TI - Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1. AB - The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of alpha oscillations may occur in NF1 both in terms of excessive or diminished activation patterns. PMID- 26881922 TI - On the Temperature Dependence of Enzyme-Catalyzed Rates. AB - One of the critical variables that determine the rate of any reaction is temperature. For biological systems, the effects of temperature are convoluted with myriad (and often opposing) contributions from enzyme catalysis, protein stability, and temperature-dependent regulation, for example. We have coined the phrase "macromolecular rate theory (MMRT)" to describe the temperature dependence of enzyme-catalyzed rates independent of stability or regulatory processes. Central to MMRT is the observation that enzyme-catalyzed reactions occur with significant values of DeltaCp(?) that are in general negative. That is, the heat capacity (Cp) for the enzyme-substrate complex is generally larger than the Cp for the enzyme-transition state complex. Consistent with a classical description of enzyme catalysis, a negative value for DeltaCp(?) is the result of the enzyme binding relatively weakly to the substrate and very tightly to the transition state. This observation of negative DeltaCp(?) has important implications for the temperature dependence of enzyme-catalyzed rates. Here, we lay out the fundamentals of MMRT. We present a number of hypotheses that arise directly from MMRT including a theoretical justification for the large size of enzymes and the basis for their optimum temperatures. We rationalize the behavior of psychrophilic enzymes and describe a "psychrophilic trap" which places limits on the evolution of enzymes in low temperature environments. One of the defining characteristics of biology is catalysis of chemical reactions by enzymes, and enzymes drive much of metabolism. Therefore, we also expect to see characteristics of MMRT at the level of cells, whole organisms, and even ecosystems. PMID- 26881923 TI - The BCL2 -938C>A Promoter Polymorphism Is Associated with Risk for and Time to Aseptic Loosening of Total Hip Arthroplasty. AB - Aseptic loosening is a major cause of revision surgery of total hip arthroplasty (THA). Only few host factors affecting aseptic loosening have been identified until now, although they are urgently needed to identify and possibly treat those patients at higher risk for aseptic loosening. To determine whether the functional single nucleotide polymorphism (SNP) c.-938C>A (rs2279115), located in the promoter region of the BCL2 gene has an impact on aseptic loosening of THA we genotyped and analyzed 234 patients suffering from aseptic loosening and 231 patients after primary THA. The polymorphism is associated with risk for aseptic loosening with the CC genotype at highest risk for aseptic loosening, Odds Ratio CC vs. AA 1.93, 95%CI 1.15-3.25, p = 0.013. In contrast, low risk AA genotype carriers that still developed aseptic loosening showed a significantly shorter time to aseptic loosening than patients carrying the C allele (p = 0.004). These results indicate that the BCL2 -938C>A polymorphism influences the occurrence and course of aseptic loosening and suggests this polymorphism as an interesting candidate for prospective studies and analyses in THA registers. PMID- 26881924 TI - Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies. AB - BACKGROUND: Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. METHODS: The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. FINDINGS/CONCLUSION: Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. PMID- 26881925 TI - alpha-Ketol linolenic acid (KODA) application affects endogenous abscisic acid, jasmonic acid and aromatic volatiles in grapes infected by a pathogen (Glomerella cingulata). AB - Effects of alpha-ketol linolenic acid (KODA) application on endogenous abscisic acid (ABA), jasmonic acid (JA), and aromatic volatiles were investigated in 'Kyoho' grapes (Vitis labrusca*Vitis vinifera) infected by a pathogen (Glomerella cingulata). The expressions of 9-cis-epoxycarotenoid dioxygenase (VvNCED1), ABA 8'-hydroxylase (VvCYP707A1), lipoxygenase (VvLOX), and allene oxide synthase (VvAOS) were also examined. The grape berries were dipped in 0.1mM KODA solution before inoculation with the pathogen and stored at 25 degrees C for 12 days. The development of infection was significantly suppressed upon KODA treatment. Endogenous ABA, JA and phaseic acid (PA) were induced in inoculated berries. KODA application before inoculation increased endogenous ABA, PA and JA through the activation of VvNCED1, VvCYP707A1 and VvAOS genes, respectively. In addition, terpenes, methyl salicylate (Me-SA) and C6-aldehydes such as (E)-2-hexenal and cis-3-hexenal associated with fungal resistance also increased in KODA-treated berries during storage. These results suggest that the synergistic effect of JA, ABA, and some aromatic volatiles induced by KODA application may provide resistance to pathogen infection in grape berries. PMID- 26881926 TI - An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid polymer hybrid nanoparticles for local anesthetic therapy. AB - PURPOSE: The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid-polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. METHODS: LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Their in vitro skin permeation was studied using a Franz diffusion cell mounted with depilated mouse skin in vitro. In vivo local anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. RESULTS: Compared with LA-LPs, LA-LPNs showed significantly better in vitro skin permeation ability and in vivo local anesthetic effects. CONCLUSION: The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy. PMID- 26881927 TI - Acellular dermal matrices in breast reconstructions - a literature review. AB - During the last two decades, acellular dermal matrices (ADM) have been more widely used in reconstructive procedures i.e. breast reconstructions. Several, both synthetic and biologic products derived from human, porcine and bovine tissue, have been introduced. Until this point postoperative complications for the acellular dermal matrices, as a group, have been the main focus. The purpose of this literature review is to summarize the current knowledge on the each biologic product used in breast reconstructions, including product specific complication frequencies. A systematic search of the literature was performed in the PubMed and EMBASE databases, identifying 55 relevant articles, mainly evidence level III. AlloDerm seems to be associated with severe complicating matters in the reconstructive process compared to other products. This could be due to the higher number of investigating studies relative to the others. The surgical area faces certain challenges comparing results, due to surgical variance, the data collection and follow-up. More well-defined guidelines and more high-evidence randomized studies could increase the overall level of evidence in this area. PMID- 26881928 TI - p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary. AB - BACKGROUND: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS: One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. RESULTS: The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. CONCLUSIONS: p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site. PMID- 26881929 TI - E2F1 and NF-kappaB: Key Mediators of Inflammation-associated Cancers and Potential Therapeutic Targets. AB - Inflammation is the fundamental protective response; however disordered immuno response can cause chronic human disease, including cancer. Inflammatory cells and mediators are essential to the tumor microenvironment and dissection of this complex molecular and cellular milieu may elucidate a connection between cancer and inflammation and help to identify potential novel therapeutic targets. Thus, focusing on transcription factor NF-kappaB and E2F1 in inflammation-associated cancer is urgent. NF-kappaB activation is prevalent in carcinomas, mainly driven by inflammatory cytokines in the tumor microenvironment. E2F1 is also involved in regulating immune responses. Understanding the crosstalk between the two pathways may contribute to the development of novel anti-cancer drugs. PMID- 26881930 TI - OncomicroRNAs-Mediated Tumorigenesis: Implication in Cancer Diagnosis and Targeted Therapy. AB - MicroRNAs (miRNAs) control the expression of approximately 60% of protein-coding genes and regulate cell metabolism, proliferation, differentiation, and apoptosis. Notably, aberrant expression of miRNAs contributes to several diseases including cancer. Accumulating evidence indicates that miRNAs play important roles in EMT, genesis of cancer stem cells, cancer metabolism and carcinogenesis. Aberrant expression of miRNAs triggers tumor initiation, progression and poor prognosis of cancer patients. Accordingly, oncogenic miRNAs have emerged as diagnostic biomarkers and targets for novel anti-cancer drug discovery. However, the mechanisms of miRNAs contriving tumorigenesis are not completely understood. This review aims to clarify the identification of tumorspecific miRNAs, verification of oncogenic miRNA signatures, and dynamic study of oncogenic miRNAs in cancer initiation and development. Despite sound progress in miRNA-mediated anticancer therapy, several barriers like drug stability, immunogenicity, off target effects and toxicities still remain. We hope our review could stimulate the further study of miRNAs in cancer research field, which may lead to new insights into the mechanisms of carcinogenesis and create new avenues for targeted cancer therapy. PMID- 26881931 TI - Current Development of ROS-Modulating Agents as Novel Antitumor Therapy. AB - Compared to normal cells, usually cancer cells are under higher oxidative stress. Elevating intracellular levels of reactive oxygen species (ROS) by introducing excessive ROS or inhibiting antioxidant system may enhance selectively of cancer cell killing by ROS-modulating agents through stress sensitization or stress overload. Meanwhile due to the adaptive response, normal cells may be capable of maintaining redox homeostasis under exogenous ROS. Here we review ROS-modulating agents in different mechanisms and classify them into groups by various targets for illustrating more clearly. At last, we discuss their side effects and the potential troubles of developing these agents and argue that might be an effective strategy for further exploring to modulate the unique redox regulatory mechanisms of cancer cells. PMID- 26881932 TI - MT1-MMP Activation of TGF-beta Signaling Enables Intercellular Activation of an Epithelial-mesenchymal Transition Program in Cancer. AB - Membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) is associated with cancer invasion and metastasis leading to poor patient prognosis. MT1-MMP mediates cancer cell invasion via degradation of basement membrane and extracellular matrix, and induction of cell migration. However, MT1-MMP expression in the cancer stroma can drive invasion of carcinoma cells in vivo, suggesting MT1-MMP may also promote cancer invasiveness via paracrinemediated mechanisms. A major step in cancer cell metastasis is thought to be an epithelial mesenchymal transition (EMT), in which carcinoma cells evolve from a stationary epithelial phenotype to a more motile mesenchymal phenotype. We demonstrate here that EMT is triggered by MT1-MMP-mediated activation of TGF-. signaling, involving induction of CUTL1 and subsequently, of Wnt5a. Mesenchymal-like cancer cells expressing endogenous MT1-MMP reverted to an epithelial phenotype when MT1 MMP, SMAD4, CUTL1, or Wnt5a expression or TGF-. activity was inhibited. Wnt5a knockdown in MT1- MMP expressing LNCaP cells caused decreased cell migration and cell growth in soft agar. While MT1-MMP expression did not affect total TGF-. level, MT1-MMP catalytic activity increased the availability of active TGF-., enabling MT1-MMP-expressing cells to activate the EMT in nearby cells. MT1-MMP expressing cells induced co-cultured non-MT1-MMP-expressing cells to undergo EMT by a TGF-.-dependent process. These results highlight a pathway by which tumor invasiveness may be expanded via MT1-MMP-mediated activation of TGF-. signaling, enabling autocrine and paracrine-mediated induction of EMT. PMID- 26881934 TI - Association of systolic blood pressure levels with cardiovascular and cerebrovascular events and all-cause mortality: a result from the Kailuan study. AB - OBJECTIVE: We aimed to examine the impact of different levels of systolic blood pressure (SBP) on the incidence of cardiovascular and cerebrovascular events and all-cause death in Chinese adults. PATIENTS AND METHODS: A total of 97 013 Chinese men and women from the Kailuan study were followed up with the incidence of cardiovascular and cerebrovascular events and all-cause death. The participants were categorized into nine groups on the basis of the different SBP levels (mmHg) (groups 1-9): SBP<110, 110<=SBP<120, 120<=SBP<130, 130<=SBP<140, 140<=SBP<150, 150<=SBP<160, 160<=SBP<170, 170<=SBP<180, and SBP>=180. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated from Cox regression models. RESULTS: During a mean follow-up of 4.02 years, a total of 2043 cardiovascular and cerebrovascular events and 1686 of all-cause deaths occurred. After adjustments for potential confounding factors and using group 1 as a reference, HRs (95% CIs) of total cardiovascular and cerebrovascular events for groups 2-9 were 1.35 (1.00-1.82), 1.61 (1.22-2.12), 1.54 (1.16-2.04), 2.05 (1.55-2.72), 2.47 (1.86-3.29), 3.04 (2.28-4.06), 3.93 (2.89-5.36), and 4.56 (3.39 6.15), respectively. HRs (95% CIs) of all-cause death for groups 2-9 were 0.92 (0.71-1.20), 0.95 (0.75-1.20), 1.06 (0.83-1.34), 1.18 (0.93-1.50), 1.16 (0.90 1.49), 1.39 (1.07-1.81), 1.74 (1.29-2.33), and 2.06 (1.56-2.72), respectively. CONCLUSION: An increase in the SBP levels is significantly associated with an increased risk of cardiovascular and cerebrovascular events and all-cause death. PMID- 26881933 TI - Health Literacy Measure for Adolescents (HELMA): Development and Psychometric Properties. AB - BACKGROUND: Health literacy refers to personal competencies for the access to, understanding of, appraisal of and application of health information in order to make sound decisions in everyday life. The aim of this study was to develop and evaluate the psychometric properties of an instrument for the measurement of health literacy among adolescents (the Health Literacy Measure for Adolescents HELMA). METHODS: This study was made up of two phases, qualitative and quantitative, which were carried out in 2012-2014 in Tehran, Iran. In the qualitative part of the study, in-depth interviews with 67 adolescents aged 15-18 were carried out in 4 high schools to generate the initial item pool for the survey. The content validity of the items was then assessed by an expert panel review (n = 13) and face validity was assessed by interviewing adolescents (n = 16). In the quantitative part of the study, in order to describe the psychometric properties of the scale, validity, reliability (internal consistency and test retest) and factor analysis were assessed. RESULTS: An item pool made up of 104 items was generated at the qualitative stage. After content validity was considered, this decreased to 47 items. In the quantitative stage, 582 adolescents aged 15-18 participated in the study with a mean age of 16.2 years. 51.2% of participants were females. In principal component factor analysis, 8 factors were loaded, which accounted for 53.37% of the variance observed. Reliability has been approved by alpha = 0.93 and the test-retest of the scale at two-week intervals indicated an appropriate stability for the scale (ICC = 0.93). The final questionnaire was approved with 44 items split into eight sections. The sections were titled: gain access to, reading, understanding, appraise, use, communication, self-efficacy and numeracy. CONCLUSION: The Health Literacy Measure for Adolescents (HELMA) is a valid and reliable tool for the measurement of the health literacy of adolescents aged 15-18 and can be used to evaluate different levels of functional, interactive, and critical health literacy in adolescents. PMID- 26881935 TI - Partial Reversal of Tissue Calcification and Extension of Life Span following Ammonium Nitrate Treatment of Klotho-Deficient Mice. AB - BACKGROUND/AIMS: Klotho is required for the inhibitory effect of FGF23 on 1,25(OH)2D3 formation and Klotho-hypomorphic mice (kl/kl) suffer from severe tissue calcification due to excessive 1,25(OH)2D3 formation with subsequent increase of Ca2+ and phosphate concentrations and stimulation of osteogenic signaling. The excessive tissue calcification dramatically accelerates aging and leads to premature death of the animals. Osteogenic signaling in those mice is disrupted by treatment with NH4Cl, which prevents tissue calcification and early death of kl/kl mice. The present study explored whether the beneficial effects of NH4Cl treatment could be mimicked by NH4NO3 treatment. METHODS: The kl/kl mice had free access to tap water either without or with addition of NH4NO3 (0.28 M) starting with the mating of the parental generation. Calcification of trachea, lung, kidney, stomach, heart and vessels was visualized by histology with von Kossa staining. Plasma phosphate concentration was determined utilizing photometry, blood gas and electrolytes utilizing a blood Gas and Chemistry Analysis System and plasma 1,25(OH)2D3 concentration with ELISA. RESULTS: In untreated kl/kl mice plasma 1,25(OH)2D3 and phosphate concentrations were elevated, and the mice suffered from marked calcification of all tissues analyzed. Untreated kl/kl mice further suffered from respiratory acidosis due to marked lung emphysema. NH4NO3-treatment decreased both, blood pCO2 and HCO3-, decreased calcification of trachea, lung, kidney, stomach, heart and vessels and increased the life span of kl/kl mice more than 1.7-fold (?) or 1.6-fold (?) without significantly affecting extracellular pH or plasma concentrations of 1,25(OH)2D3, Ca2+, phosphate, Na+, and K+. CONCLUSIONS: NH4NO3-treatment turns respiratory acidosis into metabolic acidosis and mitigates calcification thus leading to a substantial extension of kl/kl mice survival. PMID- 26881936 TI - Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women's Health Initiative Memory Study. AB - CONTEXT: The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio. OBJECTIVE: To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes. DESIGN: Prospective observational cohort study nested in the Women's Health Initiative Memory Study. SETTING: General population. SUBJECTS: Postmenopausal women. MAIN OUTCOME MEASURES: Self-reported incident type 2 diabetes. RESULTS: There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81-0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids. CONCLUSIONS: Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes. PMID- 26881937 TI - Regulation of Oncoprotein 18/Stathmin Signaling by ERK Concerns the Resistance to Taxol in Nonsmall Cell Lung Cancer Cells. AB - Taxol is a cytotoxic antiepithelioma chemotherapy drug widely used clinically, which results in appearing a broad range of taxol-resistant tumors. Oncoprotein 18 (Op18)/stathmin is a genetically highly conserved small-molecule cytosolic phosphoprotein and highly expressed in tumors. Extracellular signal-regulated kinase (ERK) is a main member of mitogen-activated protein kinases (MAPKs). The study demonstrated that combination of blockage of ERK signal by ERK inhibitor PD98059 and Taxol greatly promoted taxol-induced cellular apoptosis and growth inhibition, decreased the expression of Op18/stathmin and total levels of phosphor-Op18/stathmin, while weakened the cyclin-dependent kinase 2 (cdc2) activity and antiapoptotic protein Bcl-2 expression and inhibited IL-10 autocrine in taxol-resistant NCI-H1299 cells; Taxol-resistant NCI-H1299 cells expressed high levels of ERK and phosphor-ERK in contrast to taxol-sensitive CNE1 cells, and ERK mainly phosphorylated Op18/stathmin at Ser 25 site. These findings suggest that ERK-mediated Op18/stathmin is involved in taxol resistance of tumors; blockage of ERK signal improves the sensitivity of tumor cells to taxol, which provides new clues for treating taxol-resistant carcinomas. PMID- 26881938 TI - Variations in Peripherally Inserted Central Catheter Use and Outcomes in Michigan Hospitals. PMID- 26881939 TI - Acute Kidney Injury Prevention. AB - Acute kidney injury (AKI) is a condition associated with significant morbidity and mortality. The incidence of AKI is increasing due to predisposing factors (sepsis, nephrotoxins, and hypotension). This review will focus on the risk stratification of patients vulnerable to developing AKI in whom the timing of the insult is known (e.g., cardiac surgery, contrast exposure) as well as the clinical context in which the risk intensifies. The review will also focus on preventive measures and different pharmacological agents for preventing AKI. Clinical trials of pharmacological agents for the prevention of AKI are challenging. While many compounds are promising in preclinical testing, only a few compounds have been tested, and none has shown consistent results in clinical trials. This is in part due to the lack of large and well-designed trials. With well-designed clinical trials, the use of novel biomarkers and innovative therapeutic strategies, we are on the verge of improving outcomes in the prevention of AKI. PMID- 26881940 TI - Genome size variation in the genus Avena. AB - Genome size is an indicator of evolutionary distance and a metric for genome characterization. Here, we report accurate estimates of genome size in 99 accessions from 26 species of Avena. We demonstrate that the average genome size of C genome diploid species (2C = 10.26 pg) is 15% larger than that of A genome species (2C = 8.95 pg), and that this difference likely accounts for a progression of size among tetraploid species, where AB < AC < CC (average 2C = 16.76, 18.60, and 21.78 pg, respectively). All accessions from three hexaploid species with the ACD genome configuration had similar genome sizes (average 2C = 25.74 pg). Genome size was mostly consistent within species and in general agreement with current information about evolutionary distance among species. Results also suggest that most of the polyploid species in Avena have experienced genome downsizing in relation to their diploid progenitors. Genome size measurements could provide additional quality control for species identification in germplasm collections, especially in cases where diploid and polyploid species have similar morphology. PMID- 26881941 TI - Robust retention and transfer of tool construction techniques in chimpanzees (Pan troglodytes). AB - Long-term memory can be critical to a species' survival in environments with seasonal and even longer-term cycles of resource availability. The present, longitudinal study investigated whether complex tool behaviors used to gain an out-of-reach reward, following a hiatus of about 3 years and 7 months since initial experiences with a tool use task, were retained and subsequently executed more quickly by experienced than by naive chimpanzees. Ten of the 11 retested chimpanzees displayed impressive long-term procedural memory, creating elongated tools using the same methods employed years previously, either combining 2 tools or extending a single tool. The complex tool behaviors were also transferred to a different task context, showing behavioral flexibility. This represents some of the first evidence for appreciable long-term procedural memory, and improvements in the utility of complex tool manufacture in chimpanzees. Such long-term procedural memory and behavioral flexibility have important implications for the longevity and transmission of behavioral traditions. PMID- 26881942 TI - Mate call as reward: Acoustic communication signals can acquire positive reinforcing values during adulthood in female zebra finches (Taeniopygia guttata). AB - Social stimuli can have rewarding properties and promote learning. In birds, conspecific vocalizations like song can act as a reinforcer, and specific song variants can acquire particular rewarding values during early life exposure. Here we ask if, during adulthood, an acoustic signal simpler and shorter than song can become a reward for a female songbird because of its particular social value. Using an operant choice apparatus, we showed that female zebra finches display a preferential response toward their mate's calls. This reinforcing value of mate's calls could be involved in the maintenance of the monogamous pair-bond of the zebra finch. PMID- 26881943 TI - Bonobos (Pan paniscus) vocally protest against violations of social expectations. AB - Research has shown that great apes possess certain expectations about social regularities and both perceive and act according to social rules within their group. During natural and experimentally induced contexts, such as the inequitable distribution of resources, individuals also show protesting behaviors when their expectations about a social situation are violated. Despite broad interest in this topic, systematic research examining the nature of these expectations and the communicative signals individuals use to express them remains scant. Here, we addressed this by exploring whether bonobos (Pan paniscus) respond to violations of social expectations in naturally occurring social interactions, focusing on the vocal behavior of victims following socially expected and unexpected aggression. Expected aggression included conflicts over a contested resource and conflicts that were provoked by the victim. Unexpected aggression was any spontaneous, unprovoked hostility toward the victim. For each conflict, we also determined its severity and the composition of the nearby audience. We found that the acoustic and temporal structure of victim screams was individually distinct and varied significantly depending on whether or not aggression could be socially predicted. Certain acoustic parameters also varied as a function of conflict severity, but unlike social expectation, conflict severity did not discriminate scream acoustic structure overall. We found no effect of audience composition. We concluded that, beyond the physical nature of a conflict, bonobos possess certain social expectations about how they should be treated and will publicly protest with acoustically distinctive vocal signals if these expectations are violated. PMID- 26881944 TI - Brightness illusion in the guppy (Poecilia reticulata). AB - A long-standing debate surrounds the issue of whether human and nonhuman species share similar perceptual mechanisms. One experimental strategy to compare visual perception of vertebrates consists in assessing how animals react in the presence of visual illusions. To date, this methodological approach has been widely used with mammals and birds, while few studies have been reported in distantly related species, such as fish. In the present study we investigated whether fish perceive the brightness illusion, a well-known illusion occurring when 2 objects, identical in physical features, appear to be different in brightness. Twelve guppies (Poecilia reticulata) were initially trained to discriminate which rectangle was darker or lighter between 2 otherwise identical rectangles. Three different conditions were set up: neutral condition between rectangle and background (same background used for both darker and lighter rectangle); congruent condition (darker rectangle in a darker background and lighter rectangle in a lighter background); and incongruent condition (darker rectangle in a lighter background and lighter rectangle in a darker background). After reaching the learning criterion, guppies were presented with the illusory pattern: 2 identical rectangles inserted in 2 different backgrounds. Guppies previously trained to select the darker rectangle showed a significant choice of the rectangle that appears to be darker by human observers (and vice versa). The human-like performance exhibited in the presence of the illusory pattern suggests the existence of similar perceptual mechanisms between humans and fish to elaborate the brightness of objects. PMID- 26881945 TI - The role of redundant information in cultural transmission and cultural stabilization. AB - Redundant copying has been proposed as a manner to achieve the high-fidelity necessary to pass on and preserve complex traits in human cultural transmission. There are at least 2 ways to define redundant copying. One refers to the possibility of copying repeatedly the same trait over time, and another to the ability to exploit multiple layers of information pointing to the same trait during a single copying event. Using an individual-based model, we explore how redundant copying (defined as in the latter way) helps to achieve successful transmission. The authors show that increasing redundant copying increases the likelihood of accurately transmitting a behavior more than either augmenting the number of copying occasions across time or boosting the general accuracy of social learning. They also investigate how different cost functions, deriving, for example, from the need to invest more energy in cognitive processing, impact the evolution of redundant copying. The authors show that populations converge either to high-fitness/high-costs states (with high redundant copying and complex culturally transmitted behaviors; resembling human culture) or to low-fitness/low costs states (with low redundant copying and simple transmitted behaviors; resembling social learning forms typical of nonhuman animals). This outcome may help to explain why cumulative culture is rare in the animal kingdom. PMID- 26881946 TI - First-principles data set of 45,892 isolated and cation-coordinated conformers of 20 proteinogenic amino acids. AB - We present a structural data set of the 20 proteinogenic amino acids and their amino-methylated and acetylated (capped) dipeptides. Different protonation states of the backbone (uncharged and zwitterionic) were considered for the amino acids as well as varied side chain protonation states. Furthermore, we studied amino acids and dipeptides in complex with divalent cations (Ca(2+), Ba(2+), Sr(2+), Cd(2+), Pb(2+), and Hg(2+)). The database covers the conformational hierarchies of 280 systems in a wide relative energy range of up to 4 eV (390 kJ/mol), summing up to a total of 45,892 stationary points on the respective potential energy surfaces. All systems were calculated on equal first-principles footing, applying density-functional theory in the generalized gradient approximation corrected for long-range van der Waals interactions. We show good agreement to available experimental data for gas-phase ion affinities. Our curated data can be utilized, for example, for a wide comparison across chemical space of the building blocks of life, for the parametrization of protein force fields, and for the calculation of reference spectra for biophysical applications. PMID- 26881947 TI - Introducing a Third Timed Up & Go Test Trial Improves Performances of Hospitalized and Community-Dwelling Older Individuals. AB - BACKGROUND AND PURPOSE: Originally, the Timed Up & Go (TUG) test was described as including a practice trial before a timed trial, but recent studies in individuals with hip fracture have reported that performance improved with a third trial and that high intertester reliability was achieved when the fastest of 3 timed trials was used. Thus, the fastest of 3 TUG trials is recommended when testing individuals with hip fracture. To our knowledge, no study has examined the number of trials needed to achieve performance stability on the TUG test (defined as no further improvement on subsequent trials) when performed by older individuals without hip fracture. The aim of the study, therefore, was to examine whether a third TUG trial is faster than either of 2 TUG trials conducted according to standardized TUG instructions and whether the fastest of 3 trials is the most appropriate measure to apply in hospitalized and community-dwelling older individuals. METHODS: Eighty-two participants (50 from a geriatric hospital unit and 32 from an outpatient geriatric center; 52 women, 30 men) with a mean (SD) age of 83.6 (7.9) years were included in this cross-sectional study. All participants (except one from the hospital unit) performed 3 TUG trials, as fast as safely possible on the same day, and separated by up to 1-minute pauses. A rollator (4-wheeled rolling walker) was used as a standardized walking aid in the geriatric hospital unit, whereas participants used their normal walking aid (if any) in the outpatient geriatric center. RESULTS AND DISCUSSION: The fastest trial was trial 3 for 47 (57%), trial 2 for 25 (31%), and trial 1 for 10 (12%). Repeated-measures analyses of variance with Bonferroni corrections showed that TUG times improved from trial 1 to trial 3 (P < .04). In addition, the fastest of the 3 timed trials was significantly (P < .001) faster than the other 2 trials. CONCLUSION: We suggest that the fastest of the 3 TUG trials is recorded instead of the second trial in both hospitalized and community-dwelling older individuals. PMID- 26881948 TI - Age-Related Changes in Postural Sway Are Not Consistent Between Land and Aquatic Environments. AB - BACKGROUND AND PURPOSE: Quantifying how the environment (land vs water) influences age-related changes in postural sway is important for the development of new therapies that improve balance. The authors are not aware of any previous studies that have compared postural sway in an aquatic environment between age groups or when water depth and/or perturbations are incorporated into the comparison. The purpose of this study was to compare the effect of water depth and jet intensity on postural sway in older and younger adults. METHODS: Sixteen older (age = 62.8 +/- 9.56 years) and 15 younger (age = 22.5 +/- 1.85 years) adults participated. Participants stood quietly for 90 seconds on land and at various water depths and jet intensities while center of pressure (CoP) sway was recorded using a force platform. RESULTS: Statistical comparisons revealed that CoP range and area measurements were different between land and aquatic conditions (P = .04 - .001). For example, CoP sway area in chest deep water (8.51 +/- 2.97 cm) was greater than on land (2.41 +/- 1.37 cm; effect size = 2.05). Furthermore, CoP sway area at the 60% jet intensity (71.4 +/- 31.2 cm) was substantially greater than at the 20% jet intensity (12.4 +/- 6.23 cm; effect size = 1.89). Surprisingly, the proportion of change across water depths and jet intensities was not consistent between older and younger groups as indicated by significant age by environment interactions (P = .03 - .001). Follow-up tests indicated that older adults swayed less than younger adults in water at the level of the hip (effect sizes = 0.42-0.94) and when water jets were applied at a 60% jet intensity (effect sizes = 0.63-1.97). CONCLUSIONS: Water immersion to the chest with high jet intensities produces the greatest CoP sway in both groups. This is likely a result of buoyancy and perturbation intensity. Less sway in the older group may reflect a strategy that reduces degrees of freedom for this group when faced with these stability challenges. PMID- 26881949 TI - Bisulfite induced chemiluminescence of g-C3N4 nanosheets and enhanced by metal ions. AB - In this work, a novel chemiluminescence (CL) phenomenon was found: a g-C3N4 nanosheets suspension was mixed with NaHSO3 solution directly to produce luminescence, and the intensity of luminescence could be obviously enhanced by some metal ions, which was distinctly different from the phenomenon that Cu(2+) ions can quench the fluorescence of g-C3N4 nanosheets as reported before. PMID- 26881950 TI - Editorial. PMID- 26881951 TI - Why Bayesian Psychologists Should Change the Way They Use the Bayes Factor. AB - The discussion following Bem's ( 2011 ) psi research highlights that applications of the Bayes factor in psychological research are not without problems. The first problem is the omission to translate subjective prior knowledge into subjective prior distributions. In the words of Savage ( 1961 ): "they make the Bayesian omelet without breaking the Bayesian egg." The second problem occurs if the Bayesian egg is not broken: the omission to choose default prior distributions such that the ensuing inferences are well calibrated. The third problem is the adherence to inadequate rules for the interpretation of the size of the Bayes factor. The current paper will elaborate these problems and show how to avoid them using the basic hypotheses and statistical model used in the first experiment described in Bem ( 2011 ). It will be argued that a thorough investigation of these problems in the context of more encompassing hypotheses and statistical models is called for if Bayesian psychologists want to add a well founded Bayes factor to the tool kit of psychological researchers. PMID- 26881952 TI - Calibrated Bayes Factors Should Not Be Used: A Reply to Hoijtink, van Kooten, and Hulsker. AB - Hoijtink, Kooten, and Hulsker ( 2016 ) present a method for choosing the prior distribution for an analysis with Bayes factor that is based on controlling error rates, which they advocate as an alternative to our more subjective methods (Morey & Rouder, 2014 ; Rouder, Speckman, Sun, Morey, & Iverson, 2009 ; Wagenmakers, Wetzels, Borsboom, & van der Maas, 2011 ). We show that the method they advocate amounts to a simple significance test, and that the resulting Bayes factors are not interpretable. Additionally, their method fails in common circumstances, and has the potential to yield arbitrarily high Type II error rates. After critiquing their method, we outline the position on subjectivity that underlies our advocacy of Bayes factors. PMID- 26881953 TI - Bayes Factors Have Frequency Properties-This Should Not Be Ignored: A Rejoinder to Morey, Wagenmakers, and Rouder. AB - Hoijtink, van Kooten, and Hulsker ( 2016 ) outline a research agenda for Bayesian psychologists: evaluate and use the frequency properties of Bayes factors. Morey, Wagenmakers, and Rouder ( 2016 ) respond that Bayes factors calibrated using frequency properties should not be used. This paper contains the response of Hoijtink, van Kooten, and Hulsker to the criticism of Morey, Wagenmakers, and Rouder ( 2016 ). PMID- 26881954 TI - A Test by Any Other Name: P Values, Bayes Factors, and Statistical Inference. AB - Procedures used for statistical inference are receiving increased scrutiny as the scientific community studies the factors associated with insuring reproducible research. This note addresses recent negative attention directed at p values, the relationship of confidence intervals and tests, and the role of Bayesian inference and Bayes factors, with an eye toward better understanding these different strategies for statistical inference. We argue that researchers and data analysts too often resort to binary decisions (e.g., whether to reject or accept the null hypothesis) in settings where this may not be required. PMID- 26881955 TI - Moving in Parallel Toward a Modern Modeling Epistemology: Bayes Factors and Frequentist Modeling Methods. AB - The Bayesian-frequentist debate typically portrays these statistical perspectives as opposing views. However, both Bayesian and frequentist statisticians have expanded their epistemological basis away from a singular focus on the null hypothesis, to a broader perspective involving the development and comparison of competing statistical/mathematical models. For frequentists, statistical developments such as structural equation modeling and multilevel modeling have facilitated this transition. For Bayesians, the Bayes factor has facilitated this transition. The Bayes factor is treated in articles within this issue of Multivariate Behavioral Research. The current presentation provides brief commentary on those articles and more extended discussion of the transition toward a modern modeling epistemology. In certain respects, Bayesians and frequentists share common goals. PMID- 26881956 TI - Regression Mixture Models: Does Modeling the Covariance Between Independent Variables and Latent Classes Improve the Results? AB - Regression mixture models are increasingly used as an exploratory approach to identify heterogeneity in the effects of a predictor on an outcome. In this simulation study, we tested the effects of violating an implicit assumption often made in these models; that is, independent variables in the model are not directly related to latent classes. Results indicate that the major risk of failing to model the relationship between predictor and latent class was an increase in the probability of selecting additional latent classes and biased class proportions. In addition, we tested whether regression mixture models can detect a piecewise relationship between a predictor and outcome. Results suggest that these models are able to detect piecewise relations but only when the relationship between the latent class and the predictor is included in model estimation. We illustrate the implications of making this assumption through a reanalysis of applied data examining heterogeneity in the effects of family resources on academic achievement. We compare previous results (which assumed no relation between independent variables and latent class) to the model where this assumption is lifted. Implications and analytic suggestions for conducting regression mixture based on these findings are noted. PMID- 26881957 TI - Testing for Granger Causality in the Frequency Domain: A Phase Resampling Method. AB - This article introduces phase resampling, an existing but rarely used surrogate data method for making statistical inferences of Granger causality in frequency domain time series analysis. Granger causality testing is essential for establishing causal relations among variables in multivariate dynamic processes. However, testing for Granger causality in the frequency domain is challenging due to the nonlinear relation between frequency domain measures (e.g., partial directed coherence, generalized partial directed coherence) and time domain data. Through a simulation study, we demonstrate that phase resampling is a general and robust method for making statistical inferences even with short time series. With Gaussian data, phase resampling yields satisfactory type I and type II error rates in all but one condition we examine: when a small effect size is combined with an insufficient number of data points. Violations of normality lead to slightly higher error rates but are mostly within acceptable ranges. We illustrate the utility of phase resampling with two empirical examples involving multivariate electroencephalography (EEG) and skin conductance data. PMID- 26881958 TI - A Cross-Classified CFA-MTMM Model for Structurally Different and Nonindependent Interchangeable Methods. AB - Multirater (multimethod, multisource) studies are increasingly applied in psychology. Eid and colleagues (2008) proposed a multilevel confirmatory factor model for multitrait-multimethod (MTMM) data combining structurally different and multiple independent interchangeable methods (raters). In many studies, however, different interchangeable raters (e.g., peers, subordinates) are asked to rate different targets (students, supervisors), leading to violations of the independence assumption and to cross-classified data structures. In the present work, we extend the ML-CFA-MTMM model by Eid and colleagues (2008) to cross classified multirater designs. The new C4 model (Cross-Classified CTC[M-1] Combination of Methods) accounts for nonindependent interchangeable raters and enables researchers to explicitly model the interaction between targets and raters as a latent variable. Using a real data application, it is shown how credibility intervals of model parameters and different variance components can be obtained using Bayesian estimation techniques. PMID- 26881959 TI - Assessing Omitted Confounder Bias in Multilevel Mediation Models. AB - To draw valid inference about an indirect effect in a mediation model, there must be no omitted confounders. No omitted confounders means that there are no common causes of hypothesized causal relationships. When the no-omitted-confounder assumption is violated, inference about indirect effects can be severely biased and the results potentially misleading. Despite the increasing attention to address confounder bias in single-level mediation, this topic has received little attention in the growing area of multilevel mediation analysis. A formidable challenge is that the no-omitted-confounder assumption is untestable. To address this challenge, we first analytically examined the biasing effects of potential violations of this critical assumption in a two-level mediation model with random intercepts and slopes, in which all the variables are measured at Level 1. Our analytic results show that omitting a Level 1 confounder can yield misleading results about key quantities of interest, such as Level 1 and Level 2 indirect effects. Second, we proposed a sensitivity analysis technique to assess the extent to which potential violation of the no-omitted-confounder assumption might invalidate or alter the conclusions about the indirect effects observed. We illustrated the methods using an empirical study and provided computer code so that researchers can implement the methods discussed. PMID- 26881960 TI - Bayesian Data Analysis with the Bivariate Hierarchical Ornstein-Uhlenbeck Process Model. AB - In this paper, we propose a multilevel process modeling approach to describing individual differences in within-person changes over time. To characterize changes within an individual, repeated measures over time are modeled in terms of three person-specific parameters: a baseline level, intraindividual variation around the baseline, and regulatory mechanisms adjusting toward baseline. Variation due to measurement error is separated from meaningful intraindividual variation. The proposed model allows for the simultaneous analysis of longitudinal measurements of two linked variables (bivariate longitudinal modeling) and captures their relationship via two person-specific parameters. Relationships between explanatory variables and model parameters can be studied in a one-stage analysis, meaning that model parameters and regression coefficients are estimated simultaneously. Mathematical details of the approach, including a description of the core process model-the Ornstein-Uhlenbeck model are provided. We also describe a user friendly, freely accessible software program that provides a straightforward graphical interface to carry out parameter estimation and inference. The proposed approach is illustrated by analyzing data collected via self-reports on affective states. PMID- 26881961 TI - Incorporating Mobility in Growth Modeling for Multilevel and Longitudinal Item Response Data. AB - Multilevel data often cannot be represented by the strict form of hierarchy typically assumed in multilevel modeling. A common example is the case in which subjects change their group membership in longitudinal studies (e.g., students transfer schools; employees transition between different departments). In this study, cross-classified and multiple membership models for multilevel and longitudinal item response data (CCMM-MLIRD) are developed to incorporate such mobility, focusing on students' school change in large-scale longitudinal studies. Furthermore, we investigate the effect of incorrectly modeling school membership in the analysis of multilevel and longitudinal item response data. Two types of school mobility are described, and corresponding models are specified. Results of the simulation studies suggested that appropriate modeling of the two types of school mobility using the CCMM-MLIRD yielded good recovery of the parameters and improvement over models that did not incorporate mobility properly. In addition, the consequences of incorrectly modeling the school effects on the variance estimates of the random effects and the standard errors of the fixed effects depended upon mobility patterns and model specifications. Two sets of large-scale longitudinal data are analyzed to illustrate applications of the CCMM-MLIRD for each type of school mobility. PMID- 26881962 TI - ABM Clinical Protocol #26: Persistent Pain with Breastfeeding. AB - A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. PMID- 26881963 TI - Contrasting effects of a mixed-methods high-intensity interval training intervention in girl football players. AB - Little is known about the responses of girl athletes to training interventions throughout maturation. This study evaluated group and individual responses to an 8-week, mixed-methods, high-intensity interval training (HIIT) programme in girl football players. Thirty-seven players (age 13.4 +/- 1.5 years) were tested for 20-m speed, repeated-sprint ability, change-of-direction speed and level 1 yo-yo intermittent recovery (YYIR). Players were subcategorised into before-, at- and after-PHV (peak height velocity) based on maturity offset. Very likely moderate (25%; +/-90% confidence limits = 9.2) improvements occurred in YYIR, but data were unclear in players before-PHV with moderate individual differences in response. Decrements in repeated-sprint ability were most likely very large (6.5%; +/-3.2) before-PHV, and likely moderate (1.7%; +/-1.0) at-PHV. Data were unclear after-PHV. A very likely moderate (2.7%; +/-1.0) decrement occurred in change-of-direction speed at-PHV while there was a very likely increase (-2.4%; +/-1.3) in after-PHV players. Possibly small (-1.1%; +/-1.4) improvements in 20-m speed occurred before-PHV but the effect was otherwise unclear with moderate to large individual differences. These data reflect specific responses to training interventions in girls of different biological maturity, while highlighting individual responses to HIIT interventions. This can assist practitioners in providing effective training prescription. PMID- 26881965 TI - How do Chronically Ill Patients Rate Medical Care by their GPs and Specialists? Results of a Germany-wide Survey. AB - Introduction: The ability of health systems to respond to the legitimate expectations of the population regarding interpersonal and organizational aspects of healthcare - the so-called Health System Responsiveness - is considered a key competence of health systems. While various studies have assessed the responsiveness of ambulatory care, information on differences between care provided by general practitioners (GP) and specialists is still scarce. Methods: By means of a postal survey, 51 998 chronically ill persons (type 2 diabetes and/or coronary heart disease) insured by a statutory health insurance body (Techniker Krankenkasse) were surveyed regarding their experiences with GP and specialist care. An adapted version of the WHO Health System Responsiveness questionnaires was used for assessing data. Differences in the rating of specialist and GP care were analyzed using McNemar's test. Results: Responses from 13 685 patients were included in data analyses. Overall, ambulatory care was rated mostly as positive. Across all dimensions of health system responsiveness, GP care was rated statistically significantly as more positive than specialist care. Considerable differences were found in the evaluation of waiting times, involvement in decision-making and coordination of care. Conclusion: Overall, the surveyed persons were mostly satisfied with their GP and specialist care. However, some aspects of specialist care need to be optimized. PMID- 26881964 TI - Human neutrophil elastase induces MUC5AC overexpression in chronic rhinosinusitis through tumour necrosis factor-alpha converting enzyme. AB - Conclusion The HNE-TACE signalling pathway has an important role in the process of MUC5AC overexpression in chronic rhinosinusitis (CRS). Objectives To provide evidence of HNE-induced MUC5AC overexpression in CRS via TACE. Method HE and PAS staining were used to assess the pathological changes in sinus mucosa samples from CRS or normal control. HNE, TACE, and MUC5AC expression in the sinonasal mucosa was determined using immunohistochemistry (IHC) and real-time polymerase chain reaction (qRT-PCR). In addition, the MUC5AC and TACE expression was determined in a primary culture of human nasal mucosa epithelial cells in vitro. Results On HE staining, the main pathological feature in the sinus mucosa of CRS patients was hyperplasia of goblet cells, inflammatory cells, and submucosal glands. Mucosa from the two experimental groups also showed strong expression on PAS staining. IHC and qRT-PCR demonstrated that HNE, TACE, and MUC5AC expression was significantly higher in the CRS patients compared with control samples (p < 0.05). MUC5AC mRNA expression was higher in cells stimulated by HNE than in untreated cells (p < 0.05). MUC5AC mRNA expression was significantly reduced in cells pre-treated with the TACE inhibitor TAPI-1 prior to HNE stimulation, compared with untreated and HNE-stimulated cells (p < 0.01). PMID- 26881966 TI - Arbitrary cross-section SEM-cathodoluminescence imaging of growth sectors and local carrier concentrations within micro-sampled semiconductor nanorods. AB - Future one-dimensional electronics require single-crystalline semiconductor free standing nanorods grown with uniform electrical properties. However, this is currently unrealistic as each crystallographic plane of a nanorod grows at unique incorporation rates of environmental dopants, which forms axial and lateral growth sectors with different carrier concentrations. Here we propose a series of techniques that micro-sample a free-standing nanorod of interest, fabricate its arbitrary cross-sections by controlling focused ion beam incidence orientation, and visualize its internal carrier concentration map. ZnO nanorods are grown by selective area homoepitaxy in precursor aqueous solution, each of which has a (0001):+c top-plane and six {1-100}:m side-planes. Near-band-edge cathodoluminescence nanospectroscopy evaluates carrier concentration map within a nanorod at high spatial resolution (60 nm) and high sensitivity. It also visualizes +c and m growth sectors at arbitrary nanorod cross-section and history of local transient growth events within each growth sector. Our technique paves the way for well-defined bottom-up nanoelectronics. PMID- 26881968 TI - Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing. AB - WBP2 encodes the WW domain-binding protein 2 that acts as a transcriptional coactivator for estrogen receptor alpha (ESR1) and progesterone receptor (PGR). We reported that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mouse, as well as in two deaf children, each carrying two different variants in the WBP2 gene. The earliest abnormality we detect in Wbp2 deficient mice is a primary defect at inner hair cell afferent synapses. This study defines a new gene involved in the molecular pathway linking hearing impairment to hormonal signalling and provides new therapeutic targets. PMID- 26881969 TI - OTUB1 triggers lung cancer development by inhibiting RAS monoubiquitination. AB - Activation of the RAS oncogenic pathway, frequently ensuing from mutations in RAS genes, is a common event in human cancer. Recent reports demonstrate that reversible ubiquitination of RAS GTPases dramatically affects their activity, suggesting that enzymes involved in regulating RAS ubiquitination may contribute to malignant transformation. Here, we identified the de-ubiquitinase OTUB1 as a negative regulator of RAS mono- and di-ubiquitination. OTUB1 inhibits RAS ubiquitination independently of its catalytic activity resulting in sequestration of RAS on the plasma membrane. OTUB1 promotes RAS activation and tumorigenesis in wild-type RAS cells. An increase of OTUB1 expression is commonly observed in non small-cell lung carcinomas harboring wild-type KRAS and is associated with increased levels of ERK1/2 phosphorylation, high Ki67 score, and poorer patient survival. Our results strongly indicate that dysregulation of RAS ubiquitination represents an alternative mechanism of RAS activation during lung cancer development. PMID- 26881967 TI - Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic. AB - MicroRNA-10b (miR-10b) is a unique oncogenic miRNA that is highly expressed in all GBM subtypes, while absent in normal neuroglial cells of the brain. miR-10b inhibition strongly impairs proliferation and survival of cultured glioma cells, including glioma-initiating stem-like cells (GSC). Although several miR-10b targets have been identified previously, the common mechanism conferring the miR 10b-sustained viability of GSC is unknown. Here, we demonstrate that in heterogeneous GSC, miR-10b regulates cell cycle and alternative splicing, often through the non-canonical targeting via 5'UTRs of its target genes, including MBNL1-3, SART3, and RSRC1. We have further assessed the inhibition of miR-10b in intracranial human GSC-derived xenograft and murine GL261 allograft models in athymic and immunocompetent mice. Three delivery routes for the miR-10b antisense oligonucleotide inhibitors (ASO), direct intratumoral injections, continuous osmotic delivery, and systemic intravenous injections, have been explored. In all cases, the treatment with miR-10b ASO led to targets' derepression, and attenuated growth and progression of established intracranial GBM. No significant systemic toxicity was observed upon ASO administration by local or systemic routes. Our results indicate that miR-10b is a promising candidate for the development of targeted therapies against all GBM subtypes. PMID- 26881971 TI - Corrigendum. PMID- 26881970 TI - Clinical Relevance of VPAC1 Receptor Expression in Early Arthritis: Association with IL-6 and Disease Activity. AB - BACKGROUND: The vasoactive intestinal peptide (VIP) receptors VPAC1 and VPAC2 mediate anti-inflammatory and immunoregulatory responses in rheumatoid arthritis (RA). Data on the expression of these receptors could complement clinical assessment in the management of RA. Our goal was to investigate the correlation between expression of both receptors and the 28-Joint Disease Activity Score (DAS28) in peripheral blood mononuclear cells (PBMCs) from patients with early arthritis (EA). We also measured expression of IL-6 to evaluate the association between VIP receptors and systemic inflammation. METHODS: We analyzed 250 blood samples collected at any of the 5 scheduled follow-up visits from 125 patients enrolled in the Princesa Early Arthritis Register Longitudinal study. Samples from 22 healthy donors were also analyzed. Sociodemographic, clinical, and therapeutic data were systematically recorded. mRNA expression levels were determined using real-time PCR. Then, longitudinal multivariate analyses were performed. RESULTS: PBMCs from EA patients showed significantly higher expression of VPAC2 receptors at baseline compared to healthy donors (p<0.001). With time, however, VPAC2 expression tended to be significantly lower while VPAC1 receptor expression increased in correlation with a reduction in DAS28 index. Our results reveal that more severe inflammation, based on high levels of IL-6, is associated with lower expression of VPAC1 (p<0.001) and conversely with increased expression of VPAC2 (p<0.001). A major finding of this study is that expression of VPAC1 is lower in patients with increased disease activity (p = 0.001), thus making it possible to differentiate between patients with various degrees of clinical disease activity. CONCLUSION: Patients with more severe inflammation and higher disease activity show lower levels of VPAC1 expression, which is associated with patient-reported impairment. Therefore, VPAC1 is a biological marker in EA. PMID- 26881972 TI - Sample size determination with familywise control of both type I and type II errors in clinical trials. AB - The concept of controlling familywise type I and type II errors at the same time is essentially an integrated process to deal with multiplicity issues in clinical trials. The process will select a multiple testing procedure (MTP) which controls the familywise type I error and calculate the per hypothesis sample size such that the "studywise power" is maintained at desired level. The power of a study can be defined in several ways and it depends on the objective. In this article, we provide general guidance on how to make the selection of MTPs and calculate sample size simultaneously. We introduce the concept of strong and weak control of the familywise type II error and generalized familywise type II error. We also proposed the novel Bonferroni+ and optimal Bonferroni+ procedures to allocate per hypothesis type II error. We demonstrated the value of the proposed work as it cannot be replaced by simple simulations. A real clinical trial is discussed throughout the article as an example. PMID- 26881973 TI - Scintigraphic evaluation of renal functional damage in volatile substance abusers. AB - OBJECTIVE: Volatile organic compounds can be maintained easily and can cause dependency. Volatile substance abuse may cause damage by affecting several systems. The aim of our study was to evaluate renal functional damage in volatile substance abusers by diuretic renogram. METHODS: Twenty nine volatile substance abusers and 30 young healthy voluntary young men were included in our study. Technetium-99m mertiatide diuretic renogram was used to evaluate renal functions and collective system urodynamics to investigate the progress of renal functional damage. Images were evaluated visually and quantitatively. Split renal function of each kidney, time to peak activity (Tmax), and half-time for radiopharmaceutical clearance from pelvicalyceal system (T1/2), ratio of cortical and whole-kidney counts at 20-3 min, and maximum counts (T20/3 and T20/max) were compared in the two groups. RESULTS: In the study group, time to reach peak activity was statistically prolonged compared with the healthy volunteers. In the volatile substance abuser group, the average Tmax values, average T1/2 values, cortical and whole-kidney T20/3, and T20/max values were found to be prolonged compared with the control group in the diuretic renogram. There was no significant difference in the split renal function ratios between the two groups. CONCLUSION: In this study, possible renal functional damage was evaluated in volatile substance abusers by diuretic renogram. In conclusion, diuretic renogram can be useful in the evaluation of renal functional damage before blood renal function tests are affected and it could be used in the follow-up of the disease in volatile substance abusers. The results of this pilot study from our country, of course, should be supported by further clinical studies. PMID- 26881974 TI - Development of the Northwestern Esophageal Quality of Life Scale: A Hybrid Measure for Use Across Esophageal Conditions. AB - OBJECTIVES: Measures of health-related quality of life (HRQOL) in chronic esophageal conditions such as gastroesophageal reflux disease, eosinophilic esophagitis, and achalasia are widely used to measure this important patient reported outcome. We seek to leverage these existing measures to create a hybrid measure of esophageal illness HRQOL (the Northwestern Esophageal Quality of Life NEQOL), allowing for broad use across diseases while maintaining sensitivity to nuances of a specific condition. METHODS: A three-step, mixed-methods process per FDA guidelines for patient-reported outcome (PRO) development was followed: review and consolidation of existing HRQOL measure items into a single questionnaire, reliability and validity analyses (principle components factor analysis, Cronbach alpha, Guttman split-half, inter-item correlation, test-retest correlation, and Pearson's correlation with related constructs) based on responses from a representative sample of esophageal illness patients, and individual structured cognitive interviews with patients for item refinement and reduction. RESULTS: An initial 30-item measure was created. Two-hundred twelve patients completed the reliability and validity portion of the study, and 15 completed cognitive interviews. Factor analysis and item-reduction resulted in 11 items being removed from the NEQOL prior to patient interviews. Construct validity was supported by moderate and significant correlations with psychological distress and general HRQOL. Test-retest reliability was excellent. Following patient interviews, an additional 5 items were removed because of floor effects or participant feedback yielding a 14-item, single scale measure of HRQOL. CONCLUSIONS: Although more research is warranted, the NEQOL is a reliable and a valid hybrid measure of disease-specific HRQOL across several chronic esophageal conditions. PMID- 26881977 TI - The Focused Assessment With Sonography For Trauma (FAST) Examination And Pelvic Trauma: Indications And Limitations. AB - Pelvic trauma accounts for only 3% of all skeletal injuries but may have mortality as high as 45% in cases of severe trauma. Significant high-grade mechanism trauma to the pelvis must always take the abdomen into consideration for evaluation. The focused assessment with sonography for trauma (FAST) examination has been shown to be a valuable tool in assessing the unstable trauma patient with blunt abdominal injury, though its diagnostic utility is much less well-defined than in primary pelvic trauma. This systematic review explores the utility and limitations of the FAST examination in patients with blunt pelvic trauma and discusses the timing for the examination during the trauma survey. Newer techniques for emergency department management of the unstable trauma patient are also addressed. PMID- 26881975 TI - Altered Colorectal Compliance and Anorectal Physiology in Upper and Lower Motor Neurone Spinal Injury May Explain Bowel Symptom Pattern. AB - OBJECTIVES: Supraconal spinal cord injury (SCI) and lower motor neurone spinal cord injury (LMN-SCI) cause bowel dysfunction; colorectal compliance may further define its pathophysiology. The aim of this study was to investigate rectal (RC) and sigmoid (SC) compliance and anorectal physiology parameters, in these subjects. METHODS: Twenty-four SCI subjects with gut symptoms (14 RC, 10 SC) and 13 LMN-SCI subjects (9 RC, 4 SC) were compared with 20 spinal intact controls (10 RC, 10 SC). Staircase distensions were performed using a barostat. Anorectal manometry, including rectoanal inhibitory reflex (RAIR) measurement, was performed in all. Data presented as mean+/-standard error (SCI/LMN-SCI vs. controls). RESULTS: SCI subjects had a higher RC (17.0+/-1.9 vs. 10.7+/-0.5 ml/mm Hg, P<0.05) and SC (8.5+/-0.6 vs. 5.2+/-0.5 ml/mm Hg, P=0.002). LMN-SCI subjects had a lower RC (7.3+/-0.7 ml/mm Hg, P=0.0021) while SC was unchanged (8.3+/-2.2 ml/mm Hg, P>0.05). Anal resting pressure was decreased in SCI (55+/-5 vs. 79+/-7 cmH2O, P=0.0102). Anal squeeze pressure was decreased in LMN-SCI (76+/-13 vs. 154+/-21 cmH2O, P=0.0158). In SCI and LMN-SCI, the amplitude reduction of the RAIR was greater (62+/-4% and 70+/-6% vs. 44+/-3%, P=0.0007). CONCLUSIONS: Colorectal compliance abnormalities may explain gut symptoms: increased RC and SC contributing to constipation in SCI, reduced rectal compliance contributing to fecal incontinence (FI) in LMN-SCI. Reduced resting anal pressure in SCI and reduced anal squeeze pressure in LMN-SCI along with a greater RAIR amplitude reduction may be factors in FI. These co-existing abnormalities may explain symptom overlap, and represent future therapeutic targets to ameliorate neurogenic bowel dysfunction. PMID- 26881978 TI - Efforts in Epilepsy Prevention in the Last 40 Years: Lessons From a Large Nationwide Study. AB - IMPORTANCE: Prevention of new-onset epilepsy is an important public health issue and presents a pressing unmet need. It is unclear whether progress has been made in preventing new-onset epilepsy. OBJECTIVE: To determine whether progress has been made in the prevention of epilepsy in Finland during the last 40 years. DESIGN, SETTING, AND PARTICIPANTS: Using a long-term national register study of 5.04 million Finnish individuals, we looked at first-time inpatient admissions in Finland for a diagnosis of epilepsy from 1973 to 2013. Patients with epilepsy were defined by the occurrence of 2 or more unprovoked seizures. This study was conducted on July 29, 2015. MAIN OUTCOMES AND MEASURES: In Finland, patients with epilepsy are routinely hospitalized at time of diagnosis, thus providing evidence for the incidence of epilepsy. RESULTS: Of the mean 5.04 million Finnish individuals followed up for the development of epilepsy from 1973 to 2013, 100 792 people were identified as having epilepsy. Of these, 46,995 (47%) had focal epilepsy. The mean age for those included in the study was 45 years for men (interquartile range, 24-65 years) and 46 years for women (interquartile range, 23-71 years). We found no change in the incidence of epilepsy in the age range of those younger than 65 years (60 per 100,000 in 1973 and 64 per 100,000 in 2013). However, there was a significant increase in epilepsy among those older than 65 years (from 57 per 100,000 to 217 per 100,000). CONCLUSIONS AND RELEVANCE: We found no evidence that progress has been made in preventing new-onset epilepsy in those younger than 65 years in the last 40 years; in fact, there was a nearly 5 fold rise of new-onset epilepsy among the elderly population. PMID- 26881979 TI - Age-Related Changes in Binaural Interaction at Brainstem Level. AB - OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The present study investigates binaural interaction at the level of the auditory brainstem. It is hypothesized that brainstem binaural interaction deteriorates with advancing age. DESIGN: Forty-two subjects of various age participated in the study. Auditory brainstem responses (ABRs) were recorded using clicks and 500 Hz tone-bursts. ABRs were elicited by monaural right, monaural left, and binaural stimulation. Binaural interaction was investigated in two ways. First, grand averages of the binaural interaction component were computed for each age group. Second, wave V characteristics of the binaural ABR were compared with those of the summed left and right ABRs. RESULTS: Binaural interaction in the click ABR was demonstrated by shorter latencies and smaller amplitudes in the binaural compared with the summed monaural responses. For 500 Hz tone-burst ABR, no latency differences were found. However, amplitudes were significantly smaller in the binaural than summed monaural condition. An age-effect was found for 500 Hz tone-burst, but not for click ABR. CONCLUSIONS: Brainstem binaural interaction seems to decline with age. Interestingly, these changes seem to be stimulus-dependent. PMID- 26881980 TI - Auditory Impairments in HIV-Infected Children. AB - OBJECTIVES: In a cross-sectional study of human immunodeficiency virus (HIV) infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. DESIGN: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded. RESULTS: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p < 0.05) at multiple frequencies compared with HIV- subjects. No relationships were found between treatment regimens or delay in starting treatment and audiological parameters. CONCLUSIONS: As expected, children with HIV+ were more likely to have a history of ear drainage, and to have abnormal tympanograms. Similar to the adult findings, the HIV+ group did not show significantly reduced audiometric thresholds, but did have significantly lower DPOAE magnitudes. These data suggest that (1) HIV+ children often have middle ear damage which complicates understanding the direct effects of HIV on the hearing system, and (2) even when corrected for confounders DPOAEs were lower in the HIV+ group. Previous studies suggest ototoxicity from antiretroviral drugs is an unlikely cause of the reduced DPOAE magnitudes. Other possibilities include effects on efferent pathways connecting to outer hair cells or a direct effect of HIV on the cochlea. PMID- 26881981 TI - Impact of Hearing Aid Technology on Outcomes in Daily Life I: The Patients' Perspective. AB - OBJECTIVES: One of the challenges facing hearing care providers when recommending hearing aids is the choice of device technology level. Major manufacturers market families of hearing aids that are described as spanning the range from basic technology to premium technology. Premium technology hearing aids include acoustical processing capabilities (features) that are not found in basic technology instruments. These premium features are intended to yield improved hearing in daily life compared with basic-feature devices. However, independent research that establishes the incremental effectiveness of premium-feature devices compared with basic-feature devices is lacking. This research was designed to explore reported differences in hearing abilities for adults using premium- and basic-feature hearing aids in their daily lives. DESIGN: This was a single-blinded, repeated, crossover trial in which the participants were blinded. All procedures were carefully controlled to limit researcher bias. Forty-five participants used carefully fitted bilateral hearing aids for 1 month and then provided data to describe the hearing improvements or deficiencies noted in daily life. Typical participants were 70 years old with mild to moderate adult-onset hearing loss bilaterally. Each participant used four pairs of hearing aids: premium- and basic-feature devices from brands marketed by each of two major manufacturers. Participants were blinded about the devices they used and about the research questions. RESULTS: All of the outcomes were designed to capture the participant's point of view about the benefits of the hearing aids. Three types of data were collected: change in hearing-related quality of life, extent of agreement with six positively worded statements about everyday hearing with the hearing aids, and reported preferences between the premium- and basic-feature devices from each brand as well as across all four research hearing aids combined. None of these measures yielded a statistically significant difference in outcomes between premium- and basic-feature devices. Participants did not report better outcomes with premium processing with any measure. CONCLUSIONS: It could reasonably be asserted that the patient's perspective is the gold standard for hearing aid effectiveness. While the acoustical processing provided by premium features can potentially improve scores on tests conducted in contrived conditions in a laboratory, or on specific items in a questionnaire, this does not ensure that the processing will be of noteworthy benefit when the hearing aid is used in the real world challenges faced by the patient. If evidence suggests the patient cannot detect that premium features yield improvements over basic features in daily life, what is the responsibility of the provider in recommending hearing aid technology level? In the present research, there was no evidence to suggest that premium-feature devices yielded better outcomes than basic-feature devices from the patient's point of view. All of the research hearing aids were substantially, but equally, helpful. Further research is needed on this topic with other hearing aids and other manufacturers. In the meantime, providers should insist on scientifically credible independent evidence to support effectiveness claims for any hearing help devices. PMID- 26881982 TI - Independent Association of Severity of Muscle Weakness With Disability as Measured by the Health Assessment Questionnaire Disability Index in Scleroderma. AB - OBJECTIVE: To determine whether the presence and degree of muscle weakness in scleroderma is associated with disability. METHODS: The study included a cohort of 1,718 scleroderma patients who had available data on muscle strength and disability. The primary independent variable was muscle weakness as defined by the maximum Medsger muscle severity score and the outcome was disability as measured by the last recorded Health Assessment Questionnaire disability index (HAQ DI) score. Univariate regression analyses were performed to assess the association of HAQ DI scores with the Medsger muscle severity score and other scleroderma characteristics. A multivariate regression analysis was performed to determine whether an association existed between the degree of muscle weakness and disability, while controlling for confounders. RESULTS: In 1,718 patients with scleroderma, 22.8% (392 of 1,718) had muscle weakness, as defined by a Medsger muscle severity score of >=1. This subset was more likely than those without weakness to have diffuse cutaneous scleroderma (55.6% versus 35.1%; P < 0.0001), higher modified Rodnan skin thickness scores (mean +/- SD 16.3 +/- 13.7 versus 10.3 +/- 10.6; P < 0.00001), shorter disease duration (mean +/- SD 5.21 +/ 6.75 versus 6.22 +/- 7.67 years; P = 0.02), synovitis (17.7% versus 11.4%; P = 0.001), forced vital capacity <70% (46.2% versus 30.6%; P = 0.0001), and higher creatine kinase values (mean +/- SD 441 +/- 1,211 versus 151 +/- 255; P = 0.00001). Both univariate and multivariate analyses revealed that for every unit of increase in the Medsger muscle severity score, there was a clinically significant (minimum clinically important difference +/- 0.14) increase in the mean HAQ DI score at last followup visit. CONCLUSION: The presence of muscle weakness associates with several features of worse disease burden and independently associates with disability as measured by the HAQ DI. PMID- 26881983 TI - Predictors of maternal depressive symptom trajectories over the first 18 months in home visiting. AB - Maternal depression negatively impacts maternal functioning and parenting behaviors. Mothers participating in home visiting programs are at particularly elevated risk for depressive symptoms due to demographic and associated risk factors. Moreover, additional empirical evidence has demonstrated that mothers with depression do not benefit from home visiting interventions to the same extent as their peers without depression. The purpose of this study was to identify predictors of depression course in mothers participating in home visiting over the first 18 months of service. Participants were 220 low income mothers participating in a home visiting program who completed the Beck Depression Inventory-II (BDI-II) at enrollment and 9 and 18 months later. Measures of childhood maltreatment history, social support, and locus of control were also collected at enrollment. Group-based trajectory modeling revealed 3 groups labeled as minimal (63.6%), mild (30.5%), and moderate-severe (5.9%). Although a slight decrease in depressive symptoms was observed over time in the minimal and mild groups, mothers in the moderate-severe group exhibited a large increase from enrollment to 9 months that persisted through 18 months. Membership in the mild and moderate-severe groups was predicted by history of childhood maltreatment, low levels of social support, and an external locus of control. Implications of these findings for home visiting programs are discussed. (PsycINFO Database Record PMID- 26881984 TI - Risk and protective factors across multiple microsystems associated with internalizing symptoms and aggressive behavior in rural adolescents: Modeling longitudinal trajectories from the Rural Adaptation Project. AB - The current study examined risk and protective factors across microsystems that impact the development of internalizing symptoms and aggression over 4 years in a sample of culturally diverse, rural adolescents. We explored whether risk and protective factors across microsystems were associated with changes in rates of internalizing symptoms and aggressive behavior. Data came from the Rural Adaptation Project (RAP), a 5-year longitudinal panel study of more than 4,000 students from 26 public middle schools and 12 public high schools. Three level HLM models were estimated to predict internalizing symptoms (e.g., depression, anxiety) and aggression. Compared with other students, risk for internalizing symptoms and aggression was elevated for youth exposed to risk factors in the form of school hassles, parent-child conflict, peer rejection, and delinquent friends. Microsystem protective factors in the form of ethnic identity, religious orientation, and school satisfaction decreased risk for aggression, but were not associated with internalizing symptoms, whereas future orientation and parent support decreased risk for internalizing symptoms, but not aggression. Results indicate that risks for internalizing symptoms and aggression are similar, but that unique protective factors are related to these adolescent behavioral health outcomes. Implications and limitations were discussed. (PsycINFO Database Record PMID- 26881985 TI - Mesoporous Hybrid Shells of Carbonized Polyaniline/Mn2O3 as Non-Precious Efficient Oxygen Reduction Reaction Catalyst. AB - Mesoporous hybrid shells of carbonized polyaniline (CPANI)/Mn2O3 with well controlled diameter and high surface area have been synthesized through surface protected calcination processes. Originating from polystyrene template, PANI, MnO2, and SiO2 were sequentially loaded, followed by template removal and calcination, resulting in the desired CPANI/Mn2O3 hybrid shells. The introduction of SiO2 shell was established to play the determining role in maintaining the configuration during calcination process under high temperature. The CPANI/Mn2O3 hybrid shells showed outstanding electrocatalytic activity toward oxygen reduction reaction (ORR), with the onset potential at +0.974 V (versus RHE), the specific current at 60.8 mA/mg, and an overall quasi 4-electron transfer, which are comparable to those of the benchmark Pt/C. The remarkable ORR performance was attributed to the high specific surface area, the surface oxidation state of Mn, and composition-codependent behavior. PMID- 26881986 TI - Identification and Actions of a Novel Third Maresin Conjugate in Tissue Regeneration: MCTR3. AB - Maresin conjugates in tissue regeneration (MCTR) are a new family of evolutionarily conserved chemical signals that orchestrate host responses to promote tissue regeneration and resolution of infections. Herein, we identified the novel MCTR3 and established rank order potencies and matched the stereochemistries of MCTR1, MCTR2 and MCTR3 using material prepared by total organic synthesis and mediators isolated from both mouse and human systems. MCTR3 was produced from endogenous substrate by E. coli activated human macrophages and identified in sepsis patients. Each of the three synthetic MCTR dose-dependently (1-100 nM) accelerated tissue regeneration in planaria by 0.6-0.9 days. When administered at the onset or peak of inflammation, each of the MCTR promoted resolution of E. coli infections in mice. They increased bacterial phagocytosis by exudate leukocytes (~15-50%), limited neutrophil infiltration (~20-50%), promoted efferocytosis (~30%) and reduced eicosanoids. MCTR1 and MCTR2 upregulated human neutrophil and macrophage phagocytic responses where MCTR3 also proved to possess potent actions. These results establish the complete stereochemistry and rank order potencies for MCTR1, MCTR2 and MCTR3 that provide novel resolution moduli in regulating host responses to clear infections and promote tissue regeneration. PMID- 26881987 TI - Focus on Noncoding RNA Regulation of Plant-Microbe Interactions. PMID- 26881988 TI - From outgroups to allied forces: Effect of intergroup cooperation in violent and nonviolent video games on boosting favorable outgroup attitudes. AB - Here we addressed whether even violent video games can improve intergroup attitudes if played cooperatively with an outgroup, in keeping with the Contact Hypothesis. In addition, we examined potential mechanisms of this effect. In Experiment 1 (N = 77), Canadians played a violent video game (Call of Duty: Black Ops) against zombies, either cooperatively or independently (i.e., at the same time but solo) with a (supposed) University of Buffalo participant. As expected, cooperative (vs. solo) play significantly improved outgroup attitudes and pro outgroup participant behavior, effects explained by heightened 1-group recategorization (i.e., feeling psychologically on the same team and connected with the outgroup member). In Experiment 2 (N = 239), effects of cooperation (vs. solo play) held whether playing a violent or nonviolent video game. Importantly, our findings offer an engaging and pragmatic solution to the pervasive issue of setting up and negotiating opportunities for successful intergroup cooperation. PMID- 26881989 TI - "Relations between perceptual and conceptual scope: How global versus local processing fits a focus on similarity versus dissimilarity": Retraction of Forster (2009). PMID- 26881990 TI - "Local and global cross-modal influences between vision and hearing, tasting, smelling, or touching": Retraction of Forster (2011). PMID- 26881991 TI - Caveats for the spatial arrangement method: Comment on Hout, Goldinger, and Ferguson (2013). AB - The gold standard among proximity data collection methods for multidimensional scaling is the (dis)similarity rating of pairwise presented stimuli. A drawback of the pairwise method is its lengthy duration, which may cause participants to change their strategy over time, become fatigued, or disengage altogether. Hout, Goldinger, and Ferguson (2013) recently made a case for the Spatial Arrangement Method (SpAM) as an alternative to the pairwise method, arguing that it is faster and more engaging. SpAM invites participants to directly arrange stimuli on a computer screen such that the interstimuli distances are proportional to psychological proximity. Based on a reanalysis of the Hout et al. (2013), data we identify three caveats for SpAM. An investigation of the distributional characteristics of the SpAM proximity data reveals that the spatial nature of SpAM imposes structure on the data, invoking a bias against featural representations. Individual-differences scaling of the SpAM proximity data reveals that the two-dimensional nature of SpAM allows individuals to only communicate two dimensions of variation among stimuli properly, invoking a bias against high-dimensional scaling representations. Monte Carlo simulations indicate that in order to obtain reliable estimates of the group average, SpAM requires more individuals to be tested. We conclude with an overview of considerations that can inform the choice between SpAM and the pairwise method and offer suggestions on how to overcome their respective limitations. PMID- 26881992 TI - SpAM is convenient but also satisfying: Reply to Verheyen et al. (2016). AB - Hout, Goldinger, and Ferguson (2013) critically examined the spatial arrangement method (SpAM), originally proposed by Goldstone (1994), as a fast and efficient way to collect similarity data for multidimensional scaling. We found that SpAM produced high-quality data, making it an intuitive and user-friendly alternative to the classic "pairwise" method. Verheyen, Voorspoels, Vanpaemel, and Storms (2016) reexamined our data and raised 3 caveats regarding SpAM. In this reply, we suggest that Verheyen et al. mischaracterized our reported data as representing the entire range of potential SpAM data. SpAM results might appear more nuanced with modified instructions or stimuli. By contrast, the pairwise method is inherently limited because of its laborious, serial nature. We also demonstrate that, when the methods are equated in terms of required data-collection time, SpAM is clearly superior in terms of predicting classification data. We agree that caution is required when adopting a new method but suggest that fair assessment of SpAM requires a richer data set. PMID- 26881994 TI - Enhancing the Magnetic Anisotropy of Linear Cr(II) Chain Compounds Using Heavy Metal Substitutions. AB - Magnetic properties of the series of three linear, trimetallic chain compounds Cr2Cr(dpa)4Cl2, 1, Mo2Cr(dpa)4Cl2, 2, and W2Cr(dpa)4Cl2, 3 (dpa = 2,2' dipyridylamido), have been studied using variable-temperature dc and ac magnetometry and high-frequency EPR spectroscopy. All three compounds possess an S = 2 electronic ground state arising from the terminal Cr(2+) ion, which exhibits slow magnetic relaxation under an applied magnetic field, as evidenced by ac magnetic susceptibility and magnetization measurements. The slow relaxation stems from the existence of an easy-axis magnetic anisotropy, which is bolstered by the axial symmetry of the compounds and has been quantified through rigorous high-frequency EPR measurements. The magnitude of D in these compounds increases when heavier ions are substituted into the trimetallic chain; thus D = -1.640, 2.187, and -3.617 cm(-1) for Cr2Cr(dpa)4Cl2, Mo2Cr(dpa)4Cl2, and W2Cr(dpa)4Cl2, respectively. Additionally, the D value measured for W2Cr(dpa)4Cl2 is the largest yet reported for a high-spin Cr(2+) system. While earlier studies have demonstrated that ligands containing heavy atoms can enhance magnetic anisotropy, this is the first report of this phenomenon using heavy metal atoms as "ligands". PMID- 26881993 TI - Azido- and chlorido-cobalt complex as carrier-prototypes for antitumoral prodrugs. AB - Cobalt(III) complexes are well-suited systems for cytotoxic drug release under hypoxic conditions. Here, we investigate the effect of cytotoxic azide release by cobalt-containing carrier-prototypes for antitumoral prodrugs. In addition, we study the species formed after reduction of Co(3+) -> Co(2+) in the proposed models for these prodrugs. Three new complexes, [Co(III)(L)(N3)2]BF4(1), [{Co(II)(L)(N3)}2](ClO4)2(2), and [Co(II)(L)Cl]PF6(3), L=[(bis(1-methylimidazol-2 yl)methyl)(2-(pyridyl-2-yl)ethyl)amine], were synthesized and studied by several spectroscopic, spectrometric, electrochemical, and crystallographic methods. Reactivity and spectroscopic data reveal that complex 1 is able to release N3(-) either after reduction with ascorbic acid, or by ambient light irradiation, in aqueous phosphate buffer (pH6.2, 7.0 and 7.4) and acetonitrile solutions. The antitumoral activities of compounds 1-3 were tested in normoxia on MCF-7 (human breast adenocarcinoma), PC-3 (human prostate) and A-549 (human lung adenocarcinoma epithelial) cell lines, after 24h of exposure. Either complexes or NaN3 presented IC50 values higher than 200 MUM, showing lower cytotoxicity than the clinical standard antitumoral complex cisplatin, under the same conditions. Complexes 1-3 were also evaluated in hypoxia on A-549 and results indicate high IC50 data (>200 MUM) after 24h of exposure. However, an increase of cancer cell susceptibility to 1 and 2 was observed at 300 MUM. Regarding complex 3, no cytotoxic activity was observed in the same conditions. The data presented here indicate that the tridentate ligand L is able to stabilize both oxidation states of cobalt (+3 and +2). In addition, the cobalt(III) complex generates the low cytotoxic cobalt(II) species after reduction, which supports their use as as carrier prototypes for antitumoral prodrugs. PMID- 26881995 TI - De Novo Transcriptome Assembly and Characterization for the Widespread and Stress Tolerant Conifer Platycladus orientalis. AB - Platycladus orientalis, of the family Cupressaceae, is a widespread conifer throughout China and is extensively used for ecological reforestation, horticulture, and in medicine. Transcriptome assemblies are required for this ecologically important conifer for understanding genes underpinning adaptation and complex traits for breeding programs. To enrich the species' genomic resources, a de novo transcriptome sequencing was performed using Illumina paired end sequencing. In total, 104,073,506 high quality sequence reads (approximately 10.3 Gbp) were obtained, which were assembled into 228,948 transcripts and 148,867 unigenes that were longer than 200 nt. Quality assessment using CEGMA showed that the transcriptomes obtained were mostly complete for highly conserved core eukaryotic genes. Based on similarity searches with known proteins, 62,938 (42.28% of all unigenes), 42,158 (28.32%), and 23,179 (15.57%) had homologs in the Nr, GO, and KOG databases, 25,625 (17.21%) unigenes were mapped to 322 pathways by BLASTX comparison against the KEGG database and 1,941 unigenes involved in environmental signaling and stress response were identified. We also identified 43 putative terpene synthase (TPS) functional genes loci and compared them with TPSs from other species. Additionally, 5,296 simple sequence repeats (SSRs) were identified in 4,715 unigenes, which were assigned to 142 motif types. This is the first report of a complete transcriptome analysis of P. orientalis. These resources provide a foundation for further studies of adaptation mechanisms and molecular-based breeding programs. PMID- 26881997 TI - Assessing the orbital selective Mott transition with variational wave functions. AB - We study the Mott metal-insulator transition in the two-band Hubbard model with different hopping amplitudes t1 and t2 for the two orbitals on the two dimensional square lattice by using non-magnetic variational wave functions, similarly to what has been considered in the limit of infinite dimensions by dynamical mean-field theory. We work out the phase diagram at half filling (i.e. two electrons per site) as a function of R = t2/t1 and the on-site Coulomb repulsion U, for two values of the Hund's coupling J = 0 and J/U = 0.1. Our results are in good agreement with previous dynamical mean-field theory calculations, demonstrating that the non-magnetic phase diagram is only slightly modified from infinite to two spatial dimensions. Three phases are present: a metallic one, for small values of U, where both orbitals are itinerant; a Mott insulator, for large values of U, where both orbitals are localized because of the Coulomb repulsion; and the so-called orbital-selective Mott insulator (OSMI), for small values of R and intermediate Us, where one orbital is localized while the other one is still itinerant. The effect of the Hund's coupling is two-fold: on one side, it favors the full Mott phase over the OSMI; on the other side, it stabilizes the OSMI at larger values of R. PMID- 26881996 TI - Exogenous surfactant and alveolar recruitment in the treatment of the acute respiratory distress syndrome. AB - OBJECTIVE: To investigate the effect of alveolar recruitment combined with surfactant administration on children with acute respiratory distress syndrome (ARDS). MATERIAL AND METHODS: A prospective, randomized, controlled and sequential study was carried out. Group A (16 children) was treated with both the alveolar recruitment manoeuvres (ARM) and the administration of the surfactant every 8 h for 3 days; group B (15) received the usual treatment only. The alveolar recruitment was carried out by increasing positive end-expiratory pressure 2 by 2 cm H2 O to improve the transcutaneous oxygen saturation values up to 88% and 90%. Demographic data, gasometric and ventilator parameters, chest radiography and 28-day mortality were evaluated. RESULTS: There were no significant differences in baseline characteristics between groups. An hour after treatment, significant differences (P < 0.001) were observed in transcutaneous oxygen saturation (SaO2 ; Group A: 94.1%, Group B: 89.9%), PaO2 /FiO2 (212.7 and 126.4) and oxygenation index (OI; 11.4 and 18.5). After 8 h, the differences in SaO2 (Group A: 94.6%, Group B: 90.3%), PaO2 /FiO2 (225.8 and 126.9) and OI (10.8 and 18.4) were also significant (P < 0.001). From the fifth dose of the surfactant, the static compliance (P = 0.0034) and radiological images (P = 0.002) were more greatly improved in group A than in group B. Survival was significantly higher in group A (81.3%) than in group B (26.7%) (P = 0.006). CONCLUSIONS: The combined treatment of surfactant administration and ARM resulted in a better oxygenation and survival in children with ARDS than when only recruitment was used. PMID- 26881998 TI - Perfluorinated Alcohols Induce Complex Coacervation in Mixed Surfactants. AB - Recently, we reported a unique and nearly ubiquitous phenomenon of inducing simple and complex coacervation in solutions of a broad variety of individual and mixed amphiphiles and over a wide range of concentrations and mole fractions. This paper describes a novel type of biphasic separation in aqueous solutions of mixed cationic-anionic (catanionic) surfactants induced by hexafluoroisopropanol (HFIP). The test cases included mixtures of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl sulfate (SDS) (surfactants with different carbon chain lengths) as well as dodecyltrimethylammonium bromide (DTAB) with SDS (surfactants with the same carbon chain lengths). The CTAB-SDS-HFIP coacervate systems can be produced at many different mole ratios of surfactant, but DTAB-SDS-HFIP formed only coacervates at equimolar (1:1) mole ratios of DTAB and SDS. The phase transition behavior of both systems was studied over a wide range of surfactant and HFIP concentrations at the stoichiometric (1:1) mole ratio of cationic/anionic surfactants. The chemical compositions of each of the two phases (aqueous-rich and coacervate phases) were studied with regard to the concentrations of HFIP, water, and individual surfactants. It is revealed that the surfactant-rich phase (coacervate phase) contains a large percentage of fluoroalcohol relative to the aqueous phase and is enriched in both surfactants but contains a small percentage of water. Surprisingly, the concentration of water in the coacervate phase increases as the total HFIP concentration is increased while the concentration of HFIP in the coacervate phase remains relatively constant, which means a larger amount of water associated with HFIP molecules is extracted into the coacervate phase, which results in the growth of the phase. The volume of the coacervate phase increases with an increase in surfactant concentration and total HFIP %. The coacervate phase is highly enriched in the two amphiphilic ions (DTA(+) and DS(-)) whereas the two counterions (Br(-) and Na(+)) primarily reside in the aqueous-rich phase. The results suggest the formation of a catanionic complex in the coacervate phase through ion pairing with a concomitant release of the surfactant counterions (Na(+) and Br(-)) into the aqueous-rich phase. Finally, the fluorocarbon alcohol systems are contrasted with the effects of aliphatic alcohols in the mixed catanionic surfactant systems. Isopropanol does not have the same interactions as HFIP with respect to solubilization, aggregation, and phase separation of the oppositely charged surfactants. PMID- 26882000 TI - Correction to The 2.5 A Crystal Structure of the SIRT1 Catalytic Domain Bound to Nicotinamide Adenine Dinucleotide (NAD(+)) and an Indole (EX527 Analogue) Reveals a Novel Mechanism of Histone Deacetylase Inhibition. PMID- 26881999 TI - An ensemble of dynamic neural network identifiers for fault detection and isolation of gas turbine engines. AB - In this paper, a new approach for Fault Detection and Isolation (FDI) of gas turbine engines is proposed by developing an ensemble of dynamic neural network identifiers. For health monitoring of the gas turbine engine, its dynamics is first identified by constructing three separate or individual dynamic neural network architectures. Specifically, a dynamic multi-layer perceptron (MLP), a dynamic radial-basis function (RBF) neural network, and a dynamic support vector machine (SVM) are trained to individually identify and represent the gas turbine engine dynamics. Next, three ensemble-based techniques are developed to represent the gas turbine engine dynamics, namely, two heterogeneous ensemble models and one homogeneous ensemble model. It is first shown that all ensemble approaches do significantly improve the overall performance and accuracy of the developed system identification scheme when compared to each of the stand-alone solutions. The best selected stand-alone model (i.e., the dynamic RBF network) and the best selected ensemble architecture (i.e., the heterogeneous ensemble) in terms of their performances in achieving an accurate system identification are then selected for solving the FDI task. The required residual signals are generated by using both a single model-based solution and an ensemble-based solution under various gas turbine engine health conditions. Our extensive simulation studies demonstrate that the fault detection and isolation task achieved by using the residuals that are obtained from the dynamic ensemble scheme results in a significantly more accurate and reliable performance as illustrated through detailed quantitative confusion matrix analysis and comparative studies. PMID- 26882001 TI - CBr4 Mediated Oxidative C-N Bond Formation: Applied in the Synthesis of Imidazo[1,2-alpha]pyridines and Imidazo[1,2-alpha]pyrimidines. AB - The carbon tetrabromide mediated oxidative carbon-nitrogen bond formation of 2 aminopyridines or 2-aminopyrimidines with beta-keto esters or 1,3-diones, leading to a variety of complex imidazo[1,2-alpha]pyridines or imidazo[1,2 alpha]pyrimidines, is reported. The reactions were realized under mild and metal free conditions. PMID- 26882003 TI - Novel Approach to Securing Deep Brain Stimulation Leads: Technique and Analysis of Lead Migration, Breakage, and Surgical Infection. AB - BACKGROUND: Fixation of the electrode during deep brain stimulation (DBS) surgery is an important aspect of the procedure. We have developed an alternative method for securing leads that utilizes a titanium hemoclip and cement. This technique is described, and the rates of complications are compared to conventional methods of securing leads. METHODS: A total of 291 DBS operations performed by a single surgeon were retrospectively analyzed. We reviewed medical records to look for complications. We compared rates of complications based on the technique used. Re sults: 9 patients (3.1%) developed surgical site infections (SSIs), 4 (1.3%) with SSI of the internal pulse generator pocket. Of the 5 SSIs around the leads, none occurred with StimLoc and 5 (1.1%) with the novel technique. Eight patients (2.7%) required surgical readjustment of the DBS leads due to suboptimal clinical benefit; all 8 (1.8%) occurred with the novel technique. Four patients (1.4%) had lead fractures, 2 (2.2%) with StimLoc and 2 (0.5%) with the novel technique. CONCLUSIONS: We described a method for securing DBS leads and showed an acceptable incidence of hardware complications when compared to the conventional method. We feel this technique has improved cosmetic results and should be considered as a method for securing DBS leads. PMID- 26882002 TI - Inter-annual patterns of aggression and pair bonding in captive American flamingos (Phoenicopterus ruber). AB - Because zoos typically house animals for extended periods of time, longitudinal studies can play an important role in evaluating and optimizing animal care and management. For example, information on patterns of aggression and mating behavior across years can be used to monitor well-being, assess response to changes to group composition, and promote successful reproduction. Here, we report on patterns of aggression and pair bonding by American flamingos (Phoenicopterus ruber) at the Audubon Zoo, New Orleans USA across 4 years (2012 2015), a period that included a simultaneous introduction and removal of individuals in 2014. At the population level, overall rates and social network indices of aggressive interactions were relatively stable over the study period, without a strong signal of the 2014 replacement event. At the individual level, flamingos exhibited a high degree of within-individual consistency in levels of aggression initiated (W = 0.530, P < 0.001), and received (W = 0.369, P = 0.042). In terms of pair bonds, females re-paired with the same individuals across years more frequently (between 58% and 100% from year to year) than they switched mates, and no bonds were established between pre-existing and introduced individuals. These findings indicate a high degree of stability in aggression and pair bonding behavior in this population of captive flamingos, at both the population and individual level. Longitudinal studies such as this one provide an opportunity to better our understanding of flamingos and other long-lived, group living animals along with their management needs, especially in terms of maintaining social cohesion in captivity and improving captive breeding programs. PMID- 26882004 TI - Be Clear: A New Intensive Speech Treatment for Adults With Nonprogressive Dysarthria. AB - PURPOSE: This article describes the effects of a new intensive dysarthria treatment program (Be Clear) on speech intelligibility in adults with dysarthria secondary to stroke and traumatic brain injury. METHOD: A small group-repeated measures research design was used to examine the effects of treatment on the speech of 8 participants with nonprogressive dysarthria. Treatment consisted of a 1-hr prepractice session followed by 1-hr therapy sessions, 4 times per week, for 4 weeks (16 sessions). Paired-comparison ratings of speech intelligibility served as the primary outcome measure for the study. Perceptual data, quality of life, and communication partner opinion were obtained at 3 time intervals: (a) prior to treatment, (b) immediately posttreatment, and (c) 1-3 months posttreatment. RESULTS: Following treatment, group data demonstrated substantial improvements in speech intelligibility as perceived by naive listeners on a paired-comparison rating task. Word intelligibility was clinically significantly improved posttreatment and sentence intelligibility demonstrated statistically significant improvement. Communication partner ratings of speech intelligibility and overall communicative function were statistically significantly improved posttreatment. CONCLUSIONS: The results of this study suggest that this new intensive treatment may have potential as an effective intervention for nonprogressive dysarthria. However, controlled studies are required to establish treatment efficacy. PMID- 26882005 TI - Milk Oligosaccharide Variation in Sow Milk and Milk Oligosaccharide Fermentation in Piglet Intestine. AB - Porcine milk oligosaccharides (PMOs) were analyzed in six colostrum and two mature milk samples from Dutch Landrace sows. In total, 35 PMOs were recognized of which 13 were new for the PMO literature: neutral HexNAc-Hex, beta4' galactosyllactose, putative GalNAc(alpha/beta1-3)Gal(beta1-4)Glc, lacto-N fucopentaose-II, lacto-N-tetraose, galactose substituted lacto-N-neohexaose, lacto-N-hexaose and difucosyl-lacto-N-hexaose, and acidic Neu5Ac(alpha2 6)GlcNAc(beta1-3)Gal(beta1-4)Glc, sialyllacto-N-tetraose-a and -b, Neu5Ac2-Hex3, and sialyllacto-N-fucopentaose-II. PMOs were analyzed using capillary electrophoresis with laser-induced florescence detection or mass spectrometry and using liquid chromatography with mass spectrometry. Interindividual variation regarding PMO presence and concentration was observed between porcine milks. Within a limited sample set, a 43% decrease of the major PMOs was found during a 1 w lactation period. Interestingly, while some PMOs decreased, some other PMOs increased in concentration. PMOs were also monitored in fecal samples of suckling piglets. In feces of 1-2 d old piglets, few intact PMOs were found, indicating considerable PMO fermentation at early stage of life. PMID- 26882006 TI - Brief Report: Arthritis in KRN T Cell Receptor-Transgenic Mice Does Not Require Interleukin-17 or Th17 Cells. AB - OBJECTIVE: Th17 cells and interleukin-17 (IL-17) cytokine family members are implicated in the pathogenesis of many rheumatic diseases. Most studies in mouse models of inflammatory arthritis have demonstrated a key role for the proinflammatory cytokine IL-17A and its receptor, the IL-17 receptor (IL-17R) A/C heterodimer. The aim of this study was to use a rigorous genetic approach to evaluate the contribution of Th17 cells and IL-17 in the autoantibody-dependent KRN T cell receptor-transgenic mouse model of arthritis. METHODS: We bred KRN mice expressing the major histocompatibility complex class II molecule A(g7) (referred to as K/B/g7 mice) and genetically lacking the related cytokines IL-17A and IL-17F or their critical receptor subunit, IL-17RA. Using bone marrow transplantation, we generated mice in which hematopoietic cells from K/B/g7 donor mice lacked the key Th17-differentiating transcription factor, retinoic acid receptor-related orphan nuclear receptor gammat (Rorgammat). RESULTS: K/B/g7 mice lacking both IL-17A and IL-17F produced normal titers of pathogenic autoantibodies, and arthritis developed in a typical manner. Similarly, neither IL-17RA nor Rorgammat expression by hematopoietic cells was required for disease development in this model. CONCLUSION: Despite prior reports suggesting that Th17 cells and IL-17A are crucially involved in the pathogenesis of arthritis in K/BxN mice, the results presented here provide genetic evidence that IL-17A and IL-17F, IL-17RA, and Rorgammat expression by hematopoietic cells are dispensable for normal arthritis progression in the K/B/g7 mouse model system. We discuss potential explanations for the discrepancies between these 2 highly similar model systems. These findings plus those in other mouse models of arthritis provide insight regarding why therapeutic biologic agents targeting the Th17/IL-17 axis are beneficial in some human rheumatic diseases but not others. PMID- 26882007 TI - Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties. AB - To control liposomes fate and transport upon contact with biofluids, it is essential to consider several parameters affecting the synthetic and biological identity of liposomes, as well as liposome-protein corona (PC) aspects. As a powerful tool in this data mining adventure, quantitative structure-activity relationship (QSAR) approach is used to correlate physicochemical properties of liposomes and their PC fingerprints to multiple quantified biological responses. In the present study, the relationship between cellular interactions of a set of structurally diverse liposomal formulations and their physicochemical and PC properties has been investigated via linear and nonlinear QSAR models. Significant parameters affecting cellular uptake and cell viability of liposomes in two important cancer cell lines (PC3 and HeLa) have been identified. The developed QSARs have the capacity to be implemented in advanced targeted delivery of liposomal drugs. PMID- 26882008 TI - Awareness of cancer symptoms and anticipated patient interval for healthcare seeking. A comparative study of Denmark and Sweden. AB - Background Recent epidemiologic data show that Denmark has considerably poorer survival from common cancers than Sweden. This may be related to a lower awareness of cancer symptoms and longer patient intervals in Denmark than in Sweden. The aims of this study were to: 1) compare population awareness of three possible symptoms of cancer (unexplained lump or swelling, unexplained bleeding and persistent cough or hoarseness); 2) compare anticipated patient interval when noticing any breast changes, rectal bleeding and persistent cough; and 3) examine whether potential differences were noticeable in particular age groups or at particular levels of education in a Danish and Swedish population sample. Method Data were derived from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews using the Awareness and Beliefs about Cancer measure were conducted in 2011 among 3000 adults in Denmark and 3070 adults in Sweden. Results Danish respondents reported a higher awareness of two of three symptoms (i.e. unexplained lump or swelling and persistent cough or hoarseness) and a shorter anticipated patient interval for two of three symptoms studied (i.e. any breast changes and rectal bleeding) than Swedish respondents. Differences in symptom awareness and anticipated patient interval between these countries were most pronounced in highly educated respondents. Conclusion Somewhat paradoxically, the highest awareness of symptoms of cancer and the shortest anticipated patient intervals were found in Denmark, where cancer survival is lower than in Sweden. Thus, it appears that these differences in symptom awareness and anticipated patient interval do not help explain the cancer survival disparity between Denmark and Sweden. PMID- 26882009 TI - The Acute Kidney Injury to Chronic Kidney Disease Transition: A Potential Opportunity to Improve Care in Acute Kidney Injury. AB - Recent controlled trials, epidemiological analyses and basic research studies offer a comprehensive view of the short and long-term clinical repercussion of de novo acute kidney injury or AKI. While most post-AKI patients recover their baseline renal function, a significant number, approximately ~20% of those affected, will go on to develop long term illness characterized by an increase in late stage CKD, cardiovascular complications, and increased death rates. When AKI occurs in hospitalized patients, selected demographic and laboratory results can be incorporated into risk calculators that identify those at higher risk for long term complications. This review touches on some of the salient epidemiological studies of the AKI to CKD transition. It also focuses on certain recent advancements in our understanding of the biological and functional impact of AKI on the renal tubule repair mechanism, as well as the important role that genetic, epigenetic, biochemical and inflammatory events, seemingly beneficial to the re establishment of normal renal function, can be offset by mediators of progressive fibrosis and irreversible structural changes. Characterization of basic processes that mediate the AKI to CKD transition reveals promising pharmacological and biological agents that hopefully will one day be used in the early stages of AKI to prevent its deadly consequences. PMID- 26882010 TI - Comparative Analysis of Lacinutrix Genomes and Their Association with Bacterial Habitat. AB - The genus Lacinutrix, which belongs to the family Flavobacteriaceae, consists of seven bacterial species that were mainly isolated from marine life and sediments. As most bacteria in the family Flavobacteriaceae favor aerobic conditions, the seven bacterial species in the genus Lacinutrix also showed aerobic growth. We selected four monophyletic bacterial species living in a polar environment. Two of these species were isolated from sediment and two types were isolated from algae. In a comparative analysis, we investigated how these different environments were related to genomic features of these four species in the genus Lacinutrix. We found that the gene sets for glycolysis, the Krebs cycle, and oxidative phosphorylation were conserved in these four type strains. However, the presence of nitrous oxide reductase for denitrification and the absence of essential components related to thiamin biosynthesis for aerobic respiration were only found in isolates from sediment. Elevated bacterial metabolism on the surface of marine sediments might limit the oxygen penetration into sediment, and such an environment might affect the genomes of bacteria isolated from these habitats. PMID- 26882012 TI - Prevalence of hand osteoarthritis and its relationship to hand pain and grip strength in Japan: The third survey of the ROAD study. AB - OBJECTIVES: To examine the prevalence and pattern of hand osteoarthritis (HOA), and determine its relationship with grip strength and hand pain. METHODS: Among the participants of the third survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, 507 Japanese men and 1028 Japanese women were included. Radiographs of both hands were graded for osteoarthritis (OA) using the modified Kellgren-Lawrence (KL) scale. HOA was defined as the presence of at least one affected joint. The absence or presence of subchondral erosion was also scored. RESULTS: The prevalence of HOA (KL grade >=2) was 89.9% in men and 92.3% in women (p = 0.11), and it was significantly associated with age. OA in the distal interphalangeal (DIP) joint was the highest overall. After adjusting for age, sex, body mass index, and the residing area, both severity (KL grade >=3) and erosion were significantly related to low grip strength and hand pain. With regard to the joint groups, severe OA in the DIP and first carpometacarpal joints were related to hand pain. CONCLUSION: This study showed a high prevalence of radiographic HOA and a significant relationship between hand pain and the severity of HOA, in addition to erosion. PMID- 26882013 TI - The Impact of Third-Party Information on Trust: Valence, Source, and Reliability. AB - Economic exchange between strangers happens extremely frequently due to the growing number of internet transactions. In trust situations like online transactions, a trustor usually does not know whether she encounters a trustworthy trustee. However, the trustor might form beliefs about the trustee's trustworthiness by relying on third-party information. Different kinds of third party information can vary dramatically in their importance to the trustor. We ran a factorial design to study how the different characteristics of third-party information affect the trustor's decision to trust. We systematically varied unregulated third-party information regarding the source (friend or a stranger), the reliability (gossip or experiences), and the valence (positive or negative) of the information. The results show that negative information is more salient for withholding trust than positive information is for placing trust. If third party information is positive, experience of a friend has the strongest effect on trusting followed by friend's gossip. Positive information from a stranger does not matter to the trustor. With respect to negative information, the data show that even the slightest hint of an untrustworthy trustee leads to significantly less placed trust irrespective of the source or the reliability of the information. PMID- 26882011 TI - The Fungus Tremella mesenterica Encodes the Longest Metallothionein Currently Known: Gene, Protein and Metal Binding Characterization. AB - Fungal Cu-thioneins, and among them, the paradigmatic Neurospora crassa metallothionein (MT) (26 residues), were once considered as the shortest MTs--the ubiquitous, versatile metal-binding proteins--among all organisms, and thus representatives of their primeval forms. Nowadays, fungal MTs of diverse lengths and sequence features are known, following the huge heterogeneity of the Kingdom of Fungi. At the opposite end of N. crassa MT, the recently reported Cryptococcus neoformans CnMT1 and CnMT2 (122 and 186 aa) constitute the longest reported fungal MTs, having been identified as virulence factors of this pathogen. CnMTs are high-capacity Cu-thioneins that appear to be built by tandem amplification of a basic unit, a 7-Cys segment homologous to N. crassa MT. Here, we report the in silico, in vivo and in vitro study of a still longer fungal MT, belonging to Tremella mesenterica (TmMT), a saprophytic ascomycete. The TmMT gene has 10 exons, and it yields a 779-bp mature transcript that encodes a 257 residue-long protein. This MT is also built by repeated fragments, but of variable number of Cys: six units of the 7-Cys building blocks--CXCX3CSCPPGXCXCAXCP-, two fragments of six Cys, plus three Cys at the N-terminus. TmMT metal binding abilities have been analyzed through the spectrophotometric and spectrometric characterization of its recombinant Zn-, Cd- and Cu-complexes. Results allow it to be unambiguous classified as a Cu-thionein, also of extraordinary coordinating capacity. According to this feature, when the TmMT cDNA is expressed in MT-devoid yeast cells, it is capable of restoring a high Cu tolerance level. Since it is not obvious that T. mesenterica shares the same physiological needs for a high capacity Cu-binding protein with C. neoformans, the existence of this peculiar MT might be better explained on the basis of a possible role in Cu-handling for the Cu-enzymes responsible in lignin degradation pathways. PMID- 26882014 TI - Statistical modeling, optimization and characterization of solid self nanoemulsifying drug delivery system of lopinavir using design of experiment. AB - OBJECTIVE: Lopinavir (LPV), an antiretroviral protease inhibitor shows poor bioavailability because of poor aqueous solubility and extensive hepatic first pass metabolism. The aim of the present work was to investigate the potential of the solid self-nanoemulsifying drug delivery system (S-SNEDDS) in improving dissolution rate and oral bioavailability of LPV. MATERIALS AND METHODS: Liquid SNEDDS (L-SNEDDS) of LPV were prepared using Capmul MCM C8, Cremophor RH 40 and propylene glycol and their amounts were optimized by Scheffe's mixture design. L SNEDDS formulations were evaluated for different physicochemical and in vitro drug release parameters. S-SNEDDS were prepared by adsorbing L-SNEDDS on Neusilin US2 and characterized for solid-state properties. In vivo bioavailability of S SNEDDS, marketed Lopinavir + Ritonavir (LPV/RTV) formulation and pure LPV was studied in Wistar rats. Stability study of S-SNEDDS was performed as per ICH guidelines. RESULTS AND DISCUSSION: Optimized L-SNEDDS obtained by Scheffe design had drug loading 160 +/- 1.15 mg, globule size 32.9 +/- 1.45 nm and drug release >95% within 15 min. Solid state studies suggested the transformation of the crystalline drug to amorphous drug. The size and zeta potential of globules obtained on dilution S-SNEDDS remained similar to L-SNEEDS. In vivo bioavailability study revealed that S-SNEDDS has 2.97 and 1.54-folds higher bioavailability than pure LPV and LPV/RTV formulation, respectively. The optimized S-SNEDDS was found to be stable and had a shelf life of 2.85 years. CONCLUSION: The significant increase in drug dissolution and bioavailability by prepared SNEDDS suggest that the developed S-SNEDDS is a useful solid platform for improving oral bioavailability of poorly soluble LPV. PMID- 26882016 TI - Prevalence of delirium among patients at a cancer ward: Clinical risk factors and prediction by bedside cognitive tests. AB - Background Delirium is a frequent psychiatric complication to cancer, but rarely recognized by oncologists. Aims 1. To estimate the prevalence of delirium among inpatients admitted at an oncological cancer ward 2. To investigate whether simple clinical factors predict delirium 3. To examine the value of cognitive testing in the assessment of delirium. Methods On five different days, we interviewed and assessed patients admitted to a Danish cancer ward. The World Health Organization International Classification of Diseases Version 10, WHO ICD 10 Diagnostic System and the Confusion Assessment Method (CAM) were used for diagnostic categorization. Clinical information was gathered from medical records and all patients were tested with Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test. Results 81 cancer patients were assessed and 33% were diagnosed with delirium. All delirious participants were CAM positive. Poor performance on the cognitive tests was associated with delirium. Medical records describing CNS metastases, benzodiazepine or morphine treatment were associated with delirium. Conclusions Delirium is prevalent among cancer inpatients. The Mini Cognitive Test, The Clock Drawing Test, and the Digit Span Test can be used as screening tools for delirium among inpatients with cancer, but even in synergy, they lack specificity. Combining cognitive testing and attention to nurses' records might improve detection, yet further studies are needed to create a more detailed patient profile for the detection of delirium. PMID- 26882015 TI - Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial. AB - BACKGROUND: Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine. METHODS: This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673. FINDINGS/CONCLUSIONS: The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity. PMID- 26882017 TI - Dispositional optimism and therapeutic expectations in early-phase oncology trials. AB - BACKGROUND: Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. METHODS: Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. RESULTS: Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. CONCLUSIONS: High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. PMID- 26882019 TI - Incidence and predictors of incomplete revascularization in a contemporary cohort. AB - OBJECTIVES: Complete coronary revascularization has been associated with improved mortality among patients undergoing surgical bypass grafting. A similar evaluation among patients undergoing percutaneous coronary intervention (PCI) for multivessel disease has produced largely concordant results, although complete percutaneous revascularization is often not achieved in this population. The present study sought to evaluate the clinical and anatomic limitations to complete revascularization among contemporary patients undergoing percutaneous revascularization for multivessel coronary artery disease. METHODS: All patients undergoing nonemergent PCI for unprotected left main or multivessel coronary artery disease were identified at two academic medical centers from 2009 to 2012. Complete revascularization was determined through a review of the electronic medical records and corresponding coronary angiograms. The underlying reasons that precluded complete revascularization were then derived from a review of the clinical and angiographic findings. RESULTS: Among 978 patients with multivessel coronary artery disease, 267 (27%) underwent complete percutaneous coronary revascularization. Factors that prevented complete revascularization included chronic total occlusions (54%), treatment limited to the culprit lesion (24%), or persistent disease in small nondominant vessels (24%). After multivariable adjustment, the presence of a chronic total occlusion was associated with significantly reduced odds of receiving complete revascularization (adjusted odds ratio: 0.18, 95% confidence interval: 0.12-0.27). CONCLUSION: Complete percutaneous revascularization is uncommon and is hindered by the presence of chronic total occlusions or isolated treatment of an angiographic culprit lesion. Evolving interventional techniques enabling treatment of chronic total occlusions may increase the prevalence of complete percutaneous revascularization in the future. PMID- 26882018 TI - Coronary endothelial function testing provides superior discrimination compared with standard clinical risk scoring in prediction of cardiovascular events. AB - BACKGROUND: Endothelial dysfunction is regarded as the early stage of atherosclerosis and is associated with cardiovascular (CV) events. This study was designed to determine whether assessment of coronary endothelial function (CEF) is safe and can reclassify risk in patients with early coronary artery disease beyond the Framingham risk score (FRS). METHODS AND RESULTS: CEF was evaluated using intracoronary acetylcholine in 470 patients who presented with chest pain and nonobstructive coronary artery disease. CV events were assessed after a median follow-up of 9.7 years. The association between CEF and CV events was examined, and the net reclassification improvement index (NRI) was used to compare the incremental contribution of CEF when added to FRS.The mean age was 53 years, and 68% of the patients were women with a median FRS of 8. Complications (coronary dissection) occurred in three (0.6%) and CV events in 61 (13%) patients. In univariate analysis, microvascular CEF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.97, P=0.032] and epicardial CEF (HR 0.73, 95% CI 0.59-0.90, P=0.01) were found to be significant predictors of CV events, whereas FRS was not (HR 1.05, 95% CI 0.85-1.26, P=0.61). When added to FRS, microvascular CEF correctly reclassified 11.3% of patients [NRI 0.11 (95% CI 0.019-0.21)], epicardial CEF correctly reclassified 12.1% of patients [NRI 0.12 (95% CI -0.02 to 0.26)], and the combined microvascular and epicardial CEF correctly reclassified 22.8% of patients [NRI 0.23 (95% CI 0.08-0.37)]. CONCLUSION: CEF testing is safe and adds value to the FRS, with superior discrimination and risk stratification compared with FRS alone in patients presenting with chest pain or suspected ischemia. PMID- 26882020 TI - DESolve novolimus-eluting bioresorbable coronary scaffold failure assessed by frequency-domain optical coherence tomography imaging. PMID- 26882021 TI - Vacuum Ultraviolet Photodissociation and Fourier Transform-Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry: Revisited. AB - We revisited the implementation of 193 nm ultraviolet photodissociation (UVPD) within the ion cyclotron resonance (ICR) cell of a Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometer. UVPD performance characteristics were examined in the context of recent developments in the understanding of UVPD and in-cell tandem mass spectrometry. Efficient UVPD and photo-ECD of a model peptide and proteins within the ICR cell of a FT-ICR mass spectrometer are accomplished through appropriate modulation of laser pulse timing, relative to ion magnetron motion and the potential applied to an ion optical element upon which photons impinge. It is shown that UVPD yields efficient and extensive fragmentation, resulting in excellent sequence coverage for model peptide and protein cations. PMID- 26882022 TI - Genetic Homozygosity and Phenotypic Variability in Craniosynostotic Rabbits. AB - BACKGROUND: Craniosynostosis ranges in severity from single suture involvement with prenatal onset to multiple suture involvement with postnatal onset. The present study was designed to test the hypothesis that increasing homozygosity may be responsible for more severe phenotypic expression by examining the relationship between inbreeding and phenotypic expression in synostotic rabbits. METHODS: Data were obtained from 173 litters and 209 rabbits with familial craniosynostosis. Five distinct phenotypes were identified (normal n = 62; unicoronal delayed onset synostosis (DOS) n = 47; bicoronal DOS n = 21; unicoronal early onset synostosis (EOS) n = 26, and bicoronal EOS n= 53). Wright's coefficients of inbreeding (CI) were calculated using CompuPed software. Radiographs were taken at 10, 25, 42, 84, and 126 days of age to assess coronal suture, craniofacial, and skeletal growth. The relationship between CI and growth data was assessed using correlation coefficients. RESULTS: Mean CIs ranged from 15.68 (+/-2.22) in normal rabbits to 25.89 (+/-5.03) in bicoronal DOS, to 36.29 (+/-2.10) in unicoronal EOS to 42.85 (+/-2.10) in bicoronal EOS rabbits. Significant differences were noted among groups (F = 11.48; P < .001). Significant negative correlations were noted between CI and sutural and craniofacial growth at 25 (r = -.45, P < .001; and r = -.66, P < .001) through 126 (r = -.40, P < .001 and r = -.46, P < .001) days of age. CONCLUSIONS: While the synostotic phenotype is inherited in an autosomal dominant fashion in these rabbits, increasing homozygosity is associated with more severely affected phenotypes. These findings suggest that an accumulation of additional, modifier genes may determine the severity of the synostotic phenotype in rabbits. PMID- 26882023 TI - A Comparison of Nonopioid and Opioid Oral Analgesia Following Pediatric Palatoplasty. AB - OBJECTIVE: This article evaluates postoperative analgesia in pediatric palatoplasty patients using nonopioid oral medications. DESIGN: This study was a retrospective chart review. SETTING: The setting for this study was a tertiary care children's hospital. PARTICIPANTS: Study participants were pediatric patients who underwent palatoplasty procedures performed by a single surgeon. INTERVENTIONS: Interventions included nonopioid and opioid oral medications for postoperative analgesia. MAIN OUTCOME MEASURES: The adequacy of nonopioid versus opioid oral analgesia was assessed by (1) time to discontinue IV fluid, (2) total IV morphine doses for breakthrough pain, (3) daily IV morphine doses for breakthrough pain, (4) time to discharge from the hospital, and (5) perioperative weight change. Group comparisons of outcome measures were performed using a two one-sided test. RESULTS: A total of 61 patients were identified who received three standard pain regimens: acetaminophen + ibuprofen (12), hydrocodone/acetaminophen (23), and hydrocodone/acetaminophen + ibuprofen (26). There was sufficient evidence to suggest equivalence in outcome measures for acetaminophen + ibuprofen versus hydrocodone/acetaminophen and hydrocodone/acetaminophen + ibuprofen for the following: time to discontinue IV fluid (P = .02, 90% confidence interval [CI] = -0.42 to 0.17; P = .007, 90% CI = 0.28 to 0.34), daily IV morphine doses (P = .023, 90% CI = -0.83 to 0.65; P = .032, 90% CI = -0.92 to 0.28), time to discharge from the hospital (P = .017, 90% CI = -0.40 to 0.27; P = .015, 90% CI = -0.24 to 0.39), and perioperative weight change (P = .002; 90% CI = -0.25 to 0.46; P < .0001; 90% CI = -0.34 to 0.18). There was no sufficient evidence to suggest equivalence for total IV morphine doses (P = .189, 90% CI = -1.51 to 1.78; P = .169, 90% CI = -1.51 to 0.88). CONCLUSIONS: Oral acetaminophen and ibuprofen alone may provide similar analgesia to traditional regimens with reduced risks following pediatric palatoplasty. PMID- 26882024 TI - Initial Nutritional Assessment of Infants With Cleft Lip and/or Palate: Interventions and Return to Birth Weight. AB - OBJECTIVE: To assess and quantify cleft team practices with regard to nutritional support in the neonatal period Design : Retrospective review. SETTING: Tertiary pediatric hospital. PATIENTS: One hundred consecutive newborn patients with a diagnosis of cleft lip and/or cleft palate between 2009 and 2012. MAIN OUTCOME MEASURES: Birth weight, cleft type, initial cleft team weight measurements, initial feeding practices, recommended nutritional interventions, and follow-up nutritional assessments. RESULTS: All patients in the study were evaluated by a registered dietitian and an occupational feeding therapist. Average birth weight and average age at the first cleft team visit were similar for each cleft type: cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP). The calculated age (in days) for return to birth weight was significantly different between cleft types: CL = 13.58 days, CLP = 15.88 days, and CP = 21.93 days. Exclusive use of breast milk was 50% for patients with CL, 30.3% for patients with CLP, and 21.4% for patients with CP. Detailed nutritional interventions were made for 31 patients at the first visit: two with CL, 14 with CLP, and 15 with CP. CONCLUSIONS: Distinct differences were seen in neonatal weight gain between cleft types. There was significantly greater total weight gain for patients with CL at their first visit and significantly slower return to birth weight for patients with isolated CP. Patients with CL required far fewer interventions at the initial assessment and were more likely to be provided breast milk exclusively or in combination with formula. Infants with CP were far less likely to receive any breast milk. Patients with CLP and CP required frequent nutritional interventions. PMID- 26882025 TI - Cleft Lip and Cleft Palate Surgery: Malpractice Litigation Outcomes. AB - OBJECTIVE: This study examined malpractice claims related to cleft lip and cleft palate surgery to identify common allegations and injuries and reviewed financial outcomes. DESIGN: The WestlawNext legal database was analyzed for all malpractice lawsuits and settlements related to the surgical repair of cleft lip and palate. MAIN OUTCOMES MEASURES: Inclusion criteria included patients undergoing surgical repair of a primary cleft lip or palate or revision for complications of previous surgery. Data evaluated included patient demographics, type of operation performed, plaintiff allegation, nature of injury, and litigation outcomes. RESULTS: A total of 36 cases were identified, with 12 unique cases from 1981 to 2006 meeting the inclusion criteria. Six cases (50%) were decided by a jury and six by settlement. Five cases involved complications related to the specific surgery, and the other seven were associated with any surgery and perioperative care of children and adults. Cleft palate repair (50%) was the most frequently litigated surgery. Postoperative negligent supervision was the most common allegation (42%) and resulted in a payout in each case (mean = $3,126,032). Death (42%) and brain injury (25%) were the most frequent injuries reported. Financial awards were made in nine cases (after adjusting for inflation, mean = $2,470,552, range = $0 to $7,704,585). The awards were significantly larger for brain injury than other outcomes ($4,675,395 versus $1,368,131 after adjusting for inflation, P = .0101). CONCLUSION: Malpractice litigation regarding cleft lip and palate surgery is uncommon. However, significant financial awards involving perioperative brain injury have been reported. PMID- 26882026 TI - Tooth Abnormalities and Occlusal Disorders in Individuals With Frontonasal Dysplasia. AB - OBJECTIVE: Frontonasal dysplasia is a rare developmental defect of the midface, and little is known about the dental involvement in individuals with this condition. This study investigated tooth abnormalities and occlusal disorders in individuals with frontonasal dysplasia. DESIGN: Cross-sectional. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies, University of Sao Paulo, Bauru, Brazil. INTERVENTIONS: Clinical oral examination, analysis of patient records, and panoramic radiographs. PARTICIPANTS: A total of 20 individuals with frontonasal dysplasia aged 7 to 17 years. MAIN OUTCOME MEASURES: Prevalence of the several tooth abnormalities and occlusal disorders analyzed. RESULTS: A total of 19 individuals presented at least one tooth abnormality, with highly variable findings. In radiographs, 20% of individuals (all presenting oral clefts) presented agenesis of lateral incisors and second premolars. No supernumerary teeth were observed; 65% of individuals exhibited occlusal alterations, especially anterior open bite in the two individuals with median cleft lip. CONCLUSIONS: Variable clinical and radiographic alterations were observed, probably due to the large variety of phenotypic characteristics. No specific dental alteration could be related with frontonasal dysplasia. PMID- 26882027 TI - Alk7 Depleted Mice Exhibit Prolonged Cardiac Repolarization and Are Predisposed to Ventricular Arrhythmia. AB - We aimed to investigate the role of activin receptor-like kinase (ALK7) in regulating cardiac electrophysiology. Here, we showed that Alk7-/- mice exhibited prolonged QT intervals in telemetry ECG recordings. Furthermore, Langendorff perfused Alk7-/- hearts had significantly longer action potential duration (APD) and greater incidence of ventricular arrhythmia (AV) induced by burst pacing. Using whole-cell patch clamp, we found that the densities of repolarizing K+ currents Ito and IK1 were profoundly reduced in Alk7-/- ventricular cardiomyocytes. Mechanistically, the expression of Kv4.2 (a major subunit of Ito carrying channel) and KCHIP2 (a key accessory subunit of Ito carrying channel), was markedly decreased in Alk7-/- hearts. These findings suggest that endogenous expression of ALK7 is necessary to maintain repolarizing K+ currents in ventricular cardiomyocytes, and finally prevent action potential prolongation and ventricular arrhythmia. PMID- 26882029 TI - Role of Liprins in the Regulation of Tumor Cell Motility and Invasion. AB - Invasion leading to the formation of metastasis is one of the hallmarks of cancer. Analysis of different human cancers has led to the identification of the PPFIA1 gene encoding the protein liprin-alpha1, a possible player in cancer. The PPFIA1 gene is amplified in malignant tumors, including about 20% of breast cancers. Also the liprin-alpha1 protein is found overexpressed in tumors. Liprin alpha1 belongs to the liprin family of cytosolic scaffold proteins that includes four liprin-alpha, two liprin-beta members, and liprin-gamma/kazrinE. In this review we will discuss the available evidence on the role of different members of the liprin family in distinct aspects of tumor cell migration and invasion. Evidence from in vitro studies indicates that the widely expressed liprin-alpha1 protein regulates the migration and invasion of human breast cancer cells. Liprin alpha1 affects cell migration and invasion by regulating the organization of lamellipodia and invadopodia, two structures relevant to cell invasion. In the cell liprin-alpha1 forms a complex with liprin-beta1, ERC1/ELKS and LL5 proteins, which localizes at the front of migrating cells and positively regulates lamellipodia stability, and integrin-mediated focal adhesions. On the other hand, liprin-beta2 appears to play a role as tumor suppressor by inhibiting breast cancer cell motility and invasion. The available data indicate that liprins are central players in the regulation of tumor cell invasion, therefore representing interesting targets for anti-metastatic therapy. PMID- 26882028 TI - Small Molecules Targeting Ataxia Telangiectasia and Rad3-Related (ATR) Kinase: An Emerging way to Enhance Existing Cancer Therapy. AB - The main aim of current cancer research is to find a way to selectively affect the tumor cells, while leaving normal cells intact. Ataxia telangiectasia and Rad3-related kinase (ATR), a member of the phosphatidylinositol-3-related protein kinases (PIKK), represents a candidate target for achieving this goal. ATR kinase is one of the main kinases of the DNA damage response signaling pathway and responds to DNA damage caused by replication stress and various genotoxic agents (i.e. chemotherapy, ionizing radiation, ultraviolet light). ATR activation triggers cell cycle checkpoints, DNA repair and apoptosis, but also resistance of tumor cells to DNA damaging agents, through stress support under replication stress. Thus, the inhibition of ATR leads to increased effectiveness of cancer therapy and in addition enables highly selective targeting of cancer cells through synthetic lethal interactions. Despite this great potential, only a few potent and selective inhibitors of ATR kinase have been developed to date. However, those which have been developed provide great promise, and are under evaluation in many current preclinical and clinical trials. The purpose of this review is to summarize the potential of ATR inhibitors and the medicinal chemistry efforts which resulted in their identification. PMID- 26882030 TI - The Novel VEGF121-VEGF165 Fusion Attenuates Angiogenesis and Drug Resistance via Targeting VEGFR2-HIF-1alpha-VEGF165/Lon Signaling Through PI3K-AKT-mTOR Pathway. AB - Anti-angiogenesis therapy is one major approach of cancer therapies nowadays. Unfortunately, anti-angiogenesis therapy targeting VEGF-A was recently stumbled by the drugresistance that results from adaptive mechanisms, such as intratumor hypoxia. To obtain a more efficient therapeutic response, we created and identified a novel chimeric fusion of VEGF121 and VEGF165, which was connected by Fc region of human IgG1 to enhance dimerization. We found that the treatment of VEGF121-VEGF165 chimeric protein reduces proliferation, migration, invasion, and tube formation in endothelial and/or cancer cells through competing VEGF165 homodimer in a paracrine and an autocrine manner. Furthermore, the fusion protein attenuated autocrine VEGFR2-HIF-1alpha-VEGF165/Lon signaling through PI3KAKT- mTOR pathway in cancer cells. In conclusion, our data demonstrated that the chimeric VEGF121-VEGF165 arrests the tube formation of endothelial cells and interferes with tumor cell growth, migration and invasion, suggesting that it could be a potential drug as an angiogenesis antagonist in cancer therapy. The VEGF121-VEGF165 targets not only paracrine angiogenic cascade of endothelial cells but also autocrine PI3K-AKT-mTOR-mediated VEGFR2-HIF-1alpha- VEGF165/Lon signaling that drives drug resistance in tumor cells. Our study will open up the patient opportunities to combat drug resistance to antiangiogenic therapy. PMID- 26882031 TI - A National Profile of Family and Unpaid Caregivers Who Assist Older Adults With Health Care Activities. AB - IMPORTANCE: Family and unpaid caregivers commonly help older adults who are at high risk for poorly coordinated care. OBJECTIVE: To examine how caregivers' involvement in older adults' health care activities relates to caregiving responsibilities, supportive services use, and caregiving-related effects. DESIGN, SETTING, AND PARTICIPANTS: A total of 1739 family and unpaid caregivers of 1171 community-dwelling older adults with disabilities who participated in the 2011 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC). MAIN OUTCOMES AND MEASURES: Caregiving-related effects, including emotional, physical, and financial difficulty; participation restrictions in valued activities; and work productivity loss. EXPOSURES: Caregivers assisting older adults who provide substantial, some, or no help with health care, defined by coordinating care and managing medications (help with both, either, or neither activity, respectively). RESULTS: Based on NHATS and NSOC responses from 1739 family and unpaid caregivers of 1171 older adults with disabilities, weighted estimates were produced that accounted for the sampling designs of each survey. From these weighted estimates, 14.7 million caregivers assisting 7.7 million older adults, 6.5 million (44.1%) provided substantial help, 4.4 million (29.8%) provided some help, and 3.8 million (26.1%) provided no help with health care. Almost half (45.5%) of the caregivers providing substantial help with health care assisted an older adult with dementia. Caregivers providing substantial help with health care provided more hours of assistance per week than caregivers providing some or no help (28.1 vs 15.1 and 8.3 hours, P < .001 for both). The use of supportive services was low but was greater among caregivers providing substantial vs some or no help (26.7% vs 15.5% and 7.6%, P < .001 for both). In multivariable regression models adjusting for older adults' function and caregivers' sociodemographic and health characteristics, caregivers providing substantial help with health care were significantly more likely to experience emotional difficulty (adjusted odds ratio [aOR], 1.79; 95% CI, 1.20-2.66), physical difficulty (aOR, 2.03; 95% CI, 1.39 2.97), and financial difficulty (aOR, 2.21; 95% CI, 1.52-3.22) than caregivers providing no help. Compared with caregivers providing no help with health care activities, caregivers providing substantial help with health care activities were more than 5 times as likely to experience participation restrictions in valued activities (aOR, 5.32; 95% CI, 3.31-8.59) and more than 3 times as likely to experience work productivity loss (aOR, 3.14; 95% CI, 1.40-7.02). CONCLUSIONS AND RELEVANCE: Family caregivers providing substantial assistance with health care experience significant emotional difficulty and role-related effects, yet only one-quarter use supportive services. PMID- 26882034 TI - Puppy Temperament Assessments Predict Breed and American Kennel Club Group but Not Adult Temperament. AB - Puppy assessments for companion dogs have shown mixed long-term reliability. Temperament is cited among the reasons for surrendering dogs to shelters. A puppy temperament test that reliably predicts adult behavior is one potential way to lower the number of dogs given to shelters. This study used a longitudinal design to assess temperament in puppies from 8 different breeds at 7 weeks old (n = 52) and 6 years old (n = 34) using modified temperament tests, physiological measures, and a follow-up questionnaire. For 7-week-old puppies, results revealed (a) puppy breed was predictable using 3 variables, (b) 4 American Kennel Club breed groups had some validity based on temperament, (c) temperament was variable within litters of puppies, and (d) certain measures of temperament were related to physiological measures (heart rate). Finally, puppy temperament assessments were reliable in predicting the scores of 2 of the 8 adult dog temperament measures. However, overall, the puppy temperament scores were unreliable in predicting adult temperament. PMID- 26882032 TI - An Age-Standardized Prevalence Estimate and a Sex and Age Distribution of Myotonic Dystrophy Types 1 and 2 in the Rome Province, Italy. AB - BACKGROUND: Prevalence estimates for the 2 forms of myotonic dystrophy types 1 and 2 (DM1 and DM2) are not exhaustive or non-available. Our aim was to estimate the minimum prevalence of DM1 and DM2 in Italy in the Rome province, applying standards of descriptive epidemiology. METHODS: All patients with a molecular diagnosis of DM1/DM2 and residents in the Rome province in 2013 have been enrolled, and the age-standardized prevalence has been calculated, assuming a Poisson distribution and adjusting for age. RESULTS: We identified 395 DM1 patients: the age-standardized prevalence for total, females and males was 9.65, 8.35 and 11.07/100,000, respectively. The mean age of subjects differed considerably according to CTG repeat length (p = 0.001). Forty DM2 patients were identified. The age-standardized prevalence for total, females and males was 0.99, 1.07 and 0.90/100,000, respectively. The mean age was 57.05. CONCLUSIONS: We estimated for the first time the age-standardized prevalence and the sex and age distribution of DM1 and DM2 in a general population. A higher prevalence of males in DM1 and females in DM2 and a higher mean age of DM2 patients (+8 years) were ascertained. Prevalence of DM2 was 10% that of DM1. These prevalence values are probably lower than mutational rates due to the incomplete penetrance of DM1 mutations and to the clinical elusiveness of DM2. Our findings will be useful in designing cohort studies and for developing a disease registry. PMID- 26882033 TI - The Prevalence and Determinants of Chronic Non-Communicable Disease Risk Factors amongst Adults in the Dikgale Health Demographic and Surveillance System (HDSS) Site, Limpopo Province of South Africa. AB - BACKGROUND: The aim of the study was to determine the prevalence and determinants of chronic non-communicable disease (NCD) risk factors in a rural community in the Limpopo Province of South Africa. METHODS: This survey was conducted using the WHO "STEPwise approach to the surveillance of non-communicable diseases" (STEPS) methodology. Participants were residents of the Dikgale HDSS site and standardised international protocols were used to measure behavioural risk factors (smoking, alcohol consumption, fruit and vegetable intake and, physical activity) and physical characteristics (weight, height, waist and hip circumferences and blood pressure-BP). Fasting blood glucose, triglyceride, cholesterol and HDL-C were determined in 732 participants. Data were analysed using STATA 12 for Windows. RESULTS: The prevalence of current smokers amongst the participants was 13.7%, of which 81.3% were daily smokers. Alcohol was consumed by 16.3% of the participants. The majority of participants (88.6%) had low daily intake of fruit and vegetables and low physical activity (66.5%). The prevalence of hypertension amongst the participants was 38.2%. Overweight, obesity and high waist circumference were prevalent in females. The cardio metabolic risk profile was not significantly different between men and women. People who were older than 40 years, overweight or obese and those who consumed alcohol were more likely to be hypertensive. Smoking was associated significantly with older age, males, never married and divorced people. Alcohol consumption was associated with older age, males, low educational status and low income. CONCLUSION: High levels of risk factors for NCDs among adults in the Dikgale HDSS suggest an urgent need for health interventions to control these risk factors at the population level in order to reduce the prevalence of NCDs. PMID- 26882035 TI - Renal Recovery after Acute Kidney Injury. AB - Until recently, patients surviving an episode of acute kidney injury (AKI) were assumed to have a good renal prognosis. This belief was predominantly based on studies that used heterogeneous AKI definitions and that considered renal recovery as dialysis independence at hospital discharge. Since standardized definitions of AKI have become available, several studies have established an association between AKI and adverse clinical outcomes. It is now well recognized that while the glomerular filtration rate generally improves after AKI, the renal recovery process is often incomplete and can result in a chronic decrease in kidney function. The loss of kidney function can vary from subclinical decreases in the glomerular filtration rate to end-stage renal disease. In this chapter, we review our current understanding of renal recovery following AKI and discuss the main studies that have established associations between AKI and the development of chronic kidney disease and end-stage renal disease. PMID- 26882037 TI - Serum n-3 polyunsaturated fatty acids and psychological distress in early pregnancy: Adjunct Study of Japan Environment and Children's Study. AB - N-3 polyunsaturated fatty acids (PUFAs), especially long-chain types such as docosahexaenoic acid, are important nutrients in pregnancy, but the relationship between n-3 PUFA levels and perinatal and postnatal depression remains controversial. This study examined the possible relationship between serum n-3 PUFA levels and psychological distress among expectant mothers in early pregnancy. Data and specimen samples were obtained in a birth cohort study started at Toyama Regional Center in July 2012 as an adjunct study of the Japan Environment and Children's Study. Blood samples were collected at 9-14 weeks' gestation (75% of samples) or after 15 weeks (25%). Subjects with a Kessler Psychological Distress Scale score (K6) ? 9 were assigned to the psychological distress group (n=283). The control group (n=283) was matched for age, educational level and family income. Fatty acid composition was determined from serum samples by gas chromatography. Associations between fatty acid levels and incident psychological distress were evaluated by logistic regression. After adjusting for possible confounders, eicosapentaenoic acid showed an inverse association with risk of psychological distress, with an odds ratio of 0.47 (95% confidence interval: 0.30, 0.73) for the highest tertile. This inverse association remained even after applying a higher cutoff score (K6 ? 13) indicating severe psychological distress (74 pairs). We believe this is the first study to reveal the associations between serum n-3 PUFAs and risk of psychological distress in early pregnancy. Further research is required to verify the causality of these associations. PMID- 26882036 TI - NPY+-, but not PV+- GABAergic neurons mediated long-range inhibition from infra- to prelimbic cortex. AB - Anxiety disorders are thought to reflect deficits in the regulation of fear memories. While the amygdala has long been considered a site of storage of fear memories, newer findings suggest that the prefrontal cortex (PFC) is essential in the regulation of amygdala-dependent memories and fear expression. Here, activation of the prelimbic cortex (PrL) enhances the expression of fear, while an elevated activity in the infralimbic cortex (IL) enhances fear extinction. Despite the presence of these facts, we still know very little about the synaptic interconnectivity within the PFC. The aim of the present study was to investigate the inhibitory circuits between prelimbic and IL using morphological and electrophysiological methods. Our immunohistochemical analysis revealed that the distribution of PV(+)- and NPY(+)-GABAergic neurons was strikingly different within the PFC. In addition, we provided the first experimental evidence that the pyramidal neurons in the PrL received a direct inhibitory input mediated by bipolar NPY(+)-GABAergic projection neurons in the IL. Deletion of the anxiety related neuroligin 2 gene caused a decrease of this direct synaptic inhibition that originated from the IL. Thus, our data suggested that activation of the IL might not only directly activate the corresponding downstream anxiolytic pathway, but also suppress the PrL-related anxiogenic pathway and thus could differentially bias the regulation of fear expression and extinction. PMID- 26882039 TI - Effects of combined healthy lifestyle factors on functional vascular aging: the Rotterdam Study. AB - OBJECTIVE: To evaluate whether components of a healthy lifestyle, combined and individually, are associated with arterial stiffness as a marker of functional vascular aging. METHODS: We included 3235 participants aged 61-96 years from the Rotterdam Study. Measures of arterial stiffness included: aortic pulse wave velocity and carotid distensibility coefficient. Participants were scored one point for each of healthy lifestyle factors: consumption of five or more of fruits and/or vegetables per day, 75 min or more vigorous physical activity per week, 18.5 <= BMI <= 24. 9, never smoked and light-to-moderate alcohol intake (maximum seven glasses for women and 14 glasses for men) per week. Also a combined score (0-5) was computed by adding the five factors. Linear regression analysis was used to evaluate the association of healthy lifestyle and measures of arterial stiffness adjusting for confounders. RESULTS: Participants had -0.113 [95% confidence interval (CI): -0.196, -0.029] difference in mean aortic pulse wave velocity m/s per unit increment of the lifestyle factors score, independent of cardiovascular risk factors. Higher fruit and vegetable consumption -0.221 (95% CI: -0.409, -0.034) and physical activity -0.239 (95% CI: -0.433, -0.044) were also significantly associated with reduced aortic pulse wave velocity. The corresponding estimates in carotid distensibility coefficient lacked statistical significance when we adjusted for cardiovascular risk factors. CONCLUSION: Combining multiple healthy lifestyle factors is associated with reduced aortic stiffness, a measure of functional vascular aging and independent of cardiovascular risk factors. PMID- 26882038 TI - AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers. AB - Smoking cannabis daily doubles an individual's risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual's acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis-which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content-and also +/- 7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis. PMID- 26882040 TI - Arterial stiffness in inflammatory bowel disease: a systematic review and meta analysis. AB - BACKGROUND: Arterial stiffness is increased with chronic inflammatory disorders. The reduction of inflammation by immunomodulatory therapy is associated with a restoration of arterial function. The aims of the study were to perform a meta analysis to determine whether arterial stiffness is increased in patients with inflammatory bowel disease (IBD) and a meta-regression analysis to correlate arterial stiffness with anti-TNFalpha therapy. METHODS: Systematic review registration number: CRD42015017364. A systematic literature search for arterial stiffness in IBD was performed using PubMed, Scopus, and Google Scholar databases (last accessed on 23 September 2015). The search terms were 'arterial stiffness,' 'vascular stiffness,' or 'pulse wave velocity' in combination with 'inflammatory bowel disease,' 'inflammatory bowel diseases,' 'Crohn's disease,' or 'ulcerative colitis.' Inclusion criteria included peer-reviewed publications reporting original data, a minimum of 20 study participants tested, and pulse wave velocity (PWV) measured via validated devices. Publications with titles or abstracts appearing to meet the inclusion criteria were selected and reviewed by two authors according to PRISMA 2009 guidelines. RESULTS: Carotid-femoral PWV (cf PWV) was measured in nine cross-sectional studies (234 patients with Crohn's disease, 342 with ulcerative colitis, and 435 control study participants). Compared with control patients, cf-PWV was significantly increased in patients with Crohn's disease [mean difference 1.34 z-score; 95% confidence interval (CI) 0.71-1.97 z-score; P < 0.0001] and ulcerative colitis (mean difference 1.08 z score; 95% CI 0.55-1.61 z-score; P < 0.0001). In a meta-regression analysis, cf PWV was reduced in IBD patients treated with anti-TNFalpha therapy (beta -2.6 m/s; 95% CI -4.9 to -0.2 m/s; P = 0.03). CONCLUSION: cf-PWV is increased in both ulcerative colitis and Crohn's disease patients. PMID- 26882041 TI - Impact of left ventricular ejection function on blood pressure-lowering therapy in hypertensive patients with coronary artery disease. AB - OBJECTIVE: The prognosis of hypertensive patients with reduced left ventricular ejection fraction (LVEF) is poorer than that with normal LVEF. The influence of LVEF on blood pressure (BP)-lowering therapy remains unclear. The aim of this study was to clarify the impact of LVEF on clinical outcomes of BP-lowering therapy in hypertensive patients with coronary artery disease (CAD). METHODS: This study was a post hoc analysis from Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Heart Disease trial, a total of 2049 hypertensive patients with CAD were included. We analyzed 1849 patients with available LVEF data on enrollment. They were divided into three groups based on LVEF; reduced (<45%, n = 386), intermediate (45-55%, n = 524), and preserved (>55%, n = 999). The 'achieved SBP' was defined as the mean value of SBP in patients who did not experience major adverse cardiac events (MACE) and the mean value of SBP prior to MACE in those who experienced MACE. RESULTS: During a median follow-up period of 4.2 years, MACE rates were 30.6, 27.6, and 24.0% in the reduced, intermediate, and preserved LVEF groups, respectively. A J-shaped association between achieved SBP and MACE was observed only in the preserved LVEF group [hazard ratio of MACE in patients with lower SBP (achieved SBP < 120 mmHg) was 1.81 (1.13-2.90) compared to reference SBP patients (120 < achieved BP < 130 mmHg)], but not in the reduced or intermediate LVEF groups. CONCLUSION: In hypertensive patients with CAD, the goal of BP-lowering therapy should consider LVEF status. PMID- 26882042 TI - Axis inhibition protein 2 deficiency leads to hypoxic pulmonary hypertension through beta-catenin signaling pathway. AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) is characterized by increased vascular tone, altered vasoreactivity and vascular remodeling induced by smooth muscle cell proliferation. Similarities exist between cancer and PAH. Aberrant expression of the tumor suppressor protein is closely associated with PAH. Here, we tested the hypothesis that a tumor suppressor-axis inhibition protein 2 (Axin2) deficiency leads to PAH. METHODS AND RESULTS: We measured right ventricular systolic pressure in Axin2 knockout mice and assessed the expression of Axin2 in patients. We found that Axin2 expression level was decreased in both mice exposed to chronic hypoxia and patients with PAH in remodeled pulmonary arterioles. Axin2 knockout mice showed elevated mean right ventricular systolic pressure and enhanced contraction in response to phenylephrine. An increase in the cross-sectional area of the vessels was occupied by the vessel wall, indicating pulmonary vascular remodeling. Furthermore, knocking down Axin2 with small interfering RNA inhibited apoptosis of pulmonary arterial smooth muscle cells (PASMCs). This inhibition was significantly abolished by beta-catenin inhibitors, indicating that Axin2 through beta-catenin increased vascular wall by inhibiting the apoptosis of PASMCs. Importantly, overexpression of Axin2 attenuates the development of hypoxia-induced PAH in mice. CONCLUSION: Taken together, our study, for the first time, established that Axin2 plays a key role in the progression of PAH. We identified Axin2 as a novel mediator of pulmonary vasoconstriction and PASMC growth in hypoxia-mediated PAH. Our results suggest that downregulation of Axin2 in the pulmonary vasculature may be an underlying mechanism in the development of hypoxia-induced PAH. PMID- 26882043 TI - Maximum renal responses to renin inhibition in healthy study participants: VTP 27999 versus aliskiren. AB - BACKGROUND: Renin inhibition with aliskiren induced the largest increases in renal plasma flow (RPF) in salt-depleted healthy volunteers of all renin angiotensin system (RAS) blockers. However, given its side-effects at doses higher than 300 mg, no maximum effect of renin inhibition could be established. We hypothesized that VTP-27999, a novel renin inhibitor without major side effects at high doses, would allow us to establish this. METHODS AND RESULTS: The effects of escalating VTP-27999 doses (75-600 mg) on RPF, glomerular filtration rate (GFR), and plasma RAS components were compared with those of 300 mg aliskiren in 22 normal volunteers on a low-sodium diet. VTP-27999 dose dependently increased RPF and GFR; its effects on both parameters at 600 mg (increases of 18 +/- 4 and 20 +/- 4%, respectively) were equivalent to those at 300 mg, indicating that a maximum had been reached. The effects of 300 mg aliskiren (increases of 13 +/- 5 and 8 +/- 6%, respectively; P < 0.01 vs. 300 and 600 mg VTP-27999) resembled those of 150 mg VTP-27999. VTP-27999 dose-dependently increased renin, and lowered plasma renin activity and angiotensin II to detection limit levels. The effects of aliskiren on RAS components were best comparable to those of 150 mg VTP-27999. CONCLUSION: Maximum renal renin blockade in healthy, salt-depleted volunteers, requires aliskiren doses higher than 300 mg, but can be established with 300 mg VTP-27999. To what degree such maximal effects (exceeding those of angiotensin-converting enzyme inhibitors and AT1 receptor blockers) are required in patients with renal disease, given the potential detrimental effects of excessive RAS blockade, remains to be determined. PMID- 26882044 TI - Transient magnetorheological response of magnetoactive elastomers to step and pyramid excitations. AB - Transient rheological response of magnetoactive elastomers is experimentally studied using dynamic torsion at a fixed oscillation frequency in temporally stepwise changing magnetic fields and oscillation amplitudes. For step magnetic field excitations, at least three exponential functions are required to reasonably describe the time behavior of the storage shear modulus over long time scales (>10(3) s). The deduced characteristic time constants of the corresponding rearrangement processes of the filler network differ approximately by one order of magnitude: tau1 ? 10(1) s, tau2 ~ 10(2) s, and tau3 ~ 10(3) s. The sudden imposition of the external magnetic field activates a very fast rearrangement process with the characteristic time under 10 s, which cannot be determined more precisely due to the measurement conditions. Even more peculiar transient behavior has been observed during pyramid excitations, when either the external magnetic field was first stepwise increased and then decreased in a staircase manner at a fixed strain amplitude gamma or the strain amplitude gamma was first stepwise increased and then decreased in a staircase manner at a fixed magnetic field. In particular, the so-called "cross-over effect" has been identified in both dynamical loading programs. This cross-over effect seems to be promoted by the application of the external magnetic field. The experimental results are discussed in the context of the specific rearrangement of the magnetic filler network under the simultaneous action of the external magnetic field and shear deformation. Striking similarities of the observed phenomena to the structural relaxation processes in glassy materials and to the jamming transition of granular materials are pointed out. The obtained results are important for fundamental understanding of material behavior in magnetic fields as well as for the development of devices on the basis of magnetoactive elastomeric materials. PMID- 26882045 TI - QuantraTM should be considered a tool for two-grade scale mammographic breast density classification. AB - OBJECTIVE: To assess the agreement between QuantraTM (Hologic Inc., Bedford, MA) and Breast Imaging Reporting and Data Systems (BI-RADS((r))) and the performance of Quantra at reproducing BI-RADS mammographic breast density (MBD) assessment. METHODS: MBD assessment was performed using Quantra and BI-RADS. BI-RADS assessment was performed in two phases (1314 and 292 cases, respectively). Kappa was used to assess the interreader agreement and the agreement between Quantra and BI-RADS, and receiver-operating characteristics analysis was used to assess the performance of Quantra at reproducing BI-RADS rating. RESULTS: Agreement (weighted kappa) between BI-RADS and Quantra in Phase 1 was 0.75 [95% confidence interval (CI): 0.73-0.78] and 0.85 (95% CI: 0.80-0.90) on four- and two-grade scales, respectively. The corresponding agreement in Phase 2 was 0.79 (95% CI: 0.75-0.84) and 0.84 (95% CI: 0.79-0.87) using the majority report. In Phase 1, Quantra demonstrated 93.2% sensitivity and 86.1% specificity for BI-RADS on a two grade scale (1-2 vs 3-4). In Phase 2, it demonstrated 91.3% sensitivity and 83.6% specificity on a two-grade scale. CONCLUSION: Quantra is limited in reproducing BI-RADS rating on a four-grade scale; however, it highly reproduces BI-RADS assessment on a two-grade scale. ADVANCES IN KNOWLEDGE: Quantra (v. 2.0) is a poor predictor of BI-RADS assessment on a four-grade scale, but well reproduces BI-RADS rating on a two-grade scale. Therefore, it should be considered a tool for two-grade scale MBD classification. PMID- 26882048 TI - Corrigendum. PMID- 26882047 TI - Sonographic Assessment of the Fetal Penile Development. AB - The intrauterine diagnosis of micropenis is an important clue in the discernment of some syndromes and hormonal deficiencies. In this study, we tried to establish reference ranges for the fetal penile length and penile width. This prospective cross-sectional study included 179 healthy singleton male fetus pregnancies that were between 17 and 37 weeks of gestation. Of these pregnancies, the fetal penile length and width were measured using trans-abdominal ultrasound. The correlation coefficients of gestational age with penile measurements were calculated. We observed that as the gestational age increased both the penile length and width increased (p < .0001, correlation coefficients R(2) = 0.854 and R(2) = 0.883; respectively). Reference values of the penile length in the Turkish Population were similar to previously evaluated populations including English, American and Israeli populations. The penile width measurement is a convenient way to diagnose micropenis, but penile width measurement alone might miss some penile abnormalities including chordee and hypospadias. PMID- 26882046 TI - Screen-detected subsolid pulmonary nodules: long-term follow-up and application of the PanCan lung cancer risk prediction model. AB - OBJECTIVE: To report the long-term follow-up of subsolid nodules (SSNs) detected in participants of a prospective low-dose CT lung cancer screening cohort, and to investigate the utility of the PanCan model in stratifying risk in baseline SSNs. METHODS: Participants underwent a baseline scan, two annual incidence scans and further follow-up scans for the detected nodules. All SSNs underwent a minimum of 2 years of follow-up (unless resolved or resected). Risk of malignancy was estimated using the PanCan model; discrimination [area under the receiver operating characteristic curve (AUC)] and calibration (Hosmer-Lemeshow goodness of-fit test) were assessed. The Mann-Whitney U-Wilcoxon test was used to compare estimated risk between groups. RESULTS: 70 SSNs were detected in 41 (16.0%) out of 256 total participants. Median follow-up period was 25.5 months (range 2.0 74.0 months). 29 (41.4%) SSNs were transient. Five (7.1%) SSNs were resected, all found to be Stage I lung adenocarcinoma, including one SSN stable in size for 3.0 years before growth was detected. The PanCan model had good discrimination for the 52 baseline SSNs (AUC = 0.89; 95% confidence interval 0.76-1); the Hosmer Lemeshow goodness-of-fit test was non-significant (p = 0.27). Estimated risk was significantly higher in the baseline SSNs found to be cancer vs those not found to be cancer after 2-6 years of follow-up (p < 0.01). CONCLUSION: Our findings support a long-term follow-up approach for screen-detected SSNs for 3 years or longer. The PanCan model appeared discriminatory and well calibrated in this cohort. ADVANCES IN KNOWLEDGE: The PanCan model may have utility in identifying low-risk SSNs which could be followed with less frequent CT scans. PMID- 26882049 TI - The importance of monitoring adverse drug reactions in elderly patients: the results of a long-term pharmacovigilance programme. AB - OBJECTIVE: To recognise and prevent ADRs (including DDIs) in the elderly through a 4-year post-marketing active pharmacovigilance programme. The programme was designed to enhance high quality spontaneous reporting of ADRs in elderly patients by sampling the Italian population and was termed 'Pharmacovigilance in Geriatry (ViGer)'. METHODS: ADRs were collected for adults aged over 65 years of age treated in nursing homes, continuing care retirement communities and territorial health services in Lombardy. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analysed with respect to time, sex, category of ADR, seriousness, suspected medicines, notoriety. We analysed all the potential DDIs. RESULTS: We detected 1073 cases reports corresponding to 2110 ADRs. Vaccines, antibacterials for systemic use and antineoplastic agents were the pharmacotherapeutic subgroups most frequently involved. 18% of ADRs reports were classified as serious. In 752 reports patients were described as in polytherapy; in 55 patients (7.3%) the reported ADR were probably preventable because of DDIs involvement. CONCLUSION: The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting. PMID- 26882051 TI - Secreted Frizzled-Related Protein 4 (SFRP4) is Elevated in Patients with Diabetes Mellitus. AB - Recently, SFRP4 was identified as a molecular link between islet inflammation and defective insulin secretion. Gene co-expression analysis detected a molecule associated with type 2 diabetes mellitus (T2D), elevated HbA1c, and reduced insulin secretion in mice as well as in a pilot sample of humans. To our knowledge SFRP4 has never been investigated in patients with different types of diabetes. We included 179 patients: 46 with type 1 diabetes (T1D), 30 age matched healthy controls for patients with T1D (CO-T1D), 55 with T2D, 37 with latent autoimmune diabetes of the adult (LADA) and 30 healthy controls (CO) for patients with T2D and LADA. Apart from anthropometric data, lipids and renal parameters were assessed. SFRP4 levels were measured by a commercial ELISA. Patients with diabetes had significant higher SFRP4 levels than CO: T2D vs. CO: 37.1+/-26.7 vs. 8.8+/-3.0 ng/ml, p<0.001; LADA vs. CO: 15.6+/-6.2 vs. 8.7+/-3.0 ng/ml, p<0.001; T1D vs. CO-T1D: 24.6+/-17.9 vs. 16.9+/-4.5 ng/ml, p=0.011. SFRP4 levels were correlated with age, BMI, HbA1c, HDL-cholesterol, and triglycerides. A multivariate model revealed HDL-cholesterol, triglycerides and BMI as predictors for SFRP4. This is the first study demonstrating that SFRP4 is significantly increased in patients with different types of diabetes suggesting that this protein is generally involved in islet dysfunction and potentially subclinical inflammation irrespective of type of diabetes. PMID- 26882050 TI - Influence of Vitamin D and Parathyroid Hormone on Bone and Metabolic Risk in Women with Previous Gestational Diabetes. AB - The purpose of this study was to compare plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH), VO2max, bone (by DXA), and metabolic outcomes across age and race-matched postmenopausal women (54+/-1 years; mean+/-SEM): 1) with previous gestational diabetes (GDM) (32+/-1 kg/m(2); n=17), 2) without previous GDM, but with a similar BMI to GDM (32+/-1 kg/m(2); n=17), and 3) without previous GDM, but with a higher BMI than GDM (36+/-1 kg/m(2); n=17; p<0.01). The prevalence of 25(OH)D insufficiency and deficiency was high (~80%), but not different across groups, while PTH tended to be ~30% lower in women with a history of GDM (p=0.09). Women with a history of GDM had lower HDL cholesterol and higher diastolic blood pressure and fasting and 2-h glucose levels (by oral glucose tolerance test) (vs. groups 2 and 3; p<0.05). Bone mineral density (BMD) tended to be slightly higher in women with prior GDM than the BMI matched women with no prior GDM (p=0.09). Overall, higher PTH was associated with lower femoral neck (r=- 0.33) and (r=- 0.38) (p <0.05), while lower 25(OH)D was associated with lower VO2max (r=0.25, p=0.05) and higher fasting glucose (r=- 0.14) and insulin (r=- 0.29 (p <0.05). We observed that the poor metabolic profiles of postmenopausal women with a history of GDM are independent of 25(OH)D and PTH. However, due to associations between 25(OH)D and PTH with bone and metabolic outcomes, maintaining recommended 25(OH)D and PTH concentrations is important regardless of a previous history of GDM. PMID- 26882052 TI - Wnt signaling as potential therapeutic target in lung cancer. AB - INTRODUCTION: Wingless-type (Wnt) signaling is tightly regulated at multiple cellular levels and is dysregulated in lung cancer. Therefore, it offers therapeutic targets for developing novel agents for lung cancer treatment. AREAS COVERED: In this article, we discuss the role of the Wnt signaling pathway in lung cancer, highlighting the aberrant activation of Wnt in lung cancer stem cells and its implication in resistance to radiotherapy, chemotherapy and targeted therapy. We also expound the regulatory roles of microRNAs in Wnt signaling, as well as the potential of the Wnt pathway to provide biomarkers and therapeutic targets in lung cancer. The potential use of small molecule and biological inhibitors targeting the Wnt pathway for lung cancer therapy and prevention is also discussed. EXPERT OPINION: Wnt signaling plays an important role in the development and metastasis of lung cancer; the pathway provides targets to develop agents towards for cancer prevention and therapy. A number of clinical trials have shown the effectiveness of Wnt pathway inhibitors in epithelial tumors. However, the side effects should be considered. Nevertheless, the results from clinical studies suggest that inhibitors targeting the Wnt signaling show promise against lung cancer. PMID- 26882055 TI - Statistical inference for noninferiority of difference in proportions of clustered matched-pair data from multiple raters. AB - In clinical investigations of diagnostic procedures to indicate noninferiority, efficacy is generally evaluated on the basis of results from independent multiple raters. For each subject, if two diagnostic procedures are performed and some units are evaluated, the difference in proportions for matched-pair data is correlated between the two diagnostic procedures and within the subject, i.e. the data are clustered. In this article, we propose a noninferiority test to infer the difference in the correlated proportions of clustered data between the two diagnostic procedures. The proposed noninferiority test was validated in a Monte Carlo simulation study. Empirical sizes of the noninferiority test were close to the nominal level. The proposed test is illustrated on data of aneurysm diagnostic procedures for patients with acute subarachnoid hemorrhage. PMID- 26882053 TI - A potential hidden layer of meteorites below the ice surface of Antarctica. AB - Antarctica contains some of the most productive regions on Earth for collecting meteorites. These small areas of glacial ice are known as meteorite stranding zones, where upward-flowing ice combines with high ablation rates to concentrate large numbers of englacially transported meteorites onto their surface. However, meteorite collection data shows that iron and stony-iron meteorites are significantly under-represented from these regions as compared with all other sites on Earth. Here we explain how this discrepancy may be due to englacial solar warming, whereby meteorites a few tens of centimetres below the ice surface can be warmed up enough to cause melting of their surrounding ice and sink downwards. We show that meteorites with a high-enough thermal conductivity (for example, iron meteorites) can sink at a rate sufficient to offset the total annual upward ice transport, which may therefore permanently trap them below the ice surface and explain their absence from collection data. PMID- 26882056 TI - Giant Ocular Horn Occurring in a 10-Year-Old Female. AB - Cutaneous horns uncommonly involve the periocular region. Involvement of the ocular surface is particularly rare. The authors present a patient who underwent a perinatal buccal mucosal graft for corneal perforation due to congenital corneal ectasia, most likely resulting from Peters anomaly. She developed a giant ocular horn 10 years later. PMID- 26882057 TI - Sphenoid Wing Meningioma With Extraocular Muscle Involvement Mimicking Idiopathic Orbital Inflammation. AB - Meningiomas are slow growing, typically benign, tumors originating from arachnoid cap cells. Specifically, sphenoid wing or spheno-orbital meningiomas infiltrate the lesser wing of the sphenoid, lateral orbital wall, and orbital roof with occasional extension to the superior orbital fissure, optic canal, anterior clinoid process, and middle cranial fossa where neurologic and ophthalmologic functions are impaired by compressive injury. The extraocular muscles are rarely involved. The authors present a rare case of an spheno-orbital meningioma causing extraocular muscle enlargement mimicking idiopathic orbital inflammation and highlight important diagnostic clues to meningioma. PMID- 26882058 TI - Eyelid Mycetoma Masquerading as Sebaceous Carcinoma. AB - A 56-year-old Asian woman presented with an upper eyelid mass. The lesion was exposed after eversion of the eyelid revealing a thickened tarsus with yellowish areas. Working diagnosis was sebaceous carcinoma. Biopsy was performed. Histopathological studies showed a mycotic eumycetoma with Splendore-Hoeppli phenomena and - microbiologic cultures grew Scedosporium apiospermum. The patient was started on voriconazole 200 mg po bid with adequate serum levels. A complete response was observed after 18 weeks of voriconazole therapy. To the best of our knowledge, this is the first published case of S. apiospermum eumycotic mycetoma of the eyelid. It is important to consider mycotic infection in the differential diagnosis of eyelid tumors even in healthy patients. PMID- 26882059 TI - Nodular Fasciitis of the Orbit: A Case Report Confirmed by Molecular Cytogenetic Analysis. AB - Nodular fasciitis is a benign fibroblastic proliferation typically found in the subcutaneous tissue or superficial fascia of the extremities that is often confused for malignancy. These lesions rarely occur on the eyelids and ocular adnexa and are seldom analyzed by ophthalmic pathologists. USP6 gene rearrangement has been recently demonstrated in nodular fasciitis and this rearrangement may lead to the formation of a fusion gene MYH9-USP6 in some cases. Herein, the authors describe a 38-year-old woman with a 6-month history of a progressively enlarging mass beneath her right medial upper eyelid. Histopathologic analysis of the excisional biopsy confirmed classic features of nodular fasciitis. Molecular cytogenetic analysis revealed a rearrangement of the USP6 locus, confirming the diagnosis of benign nodular fasciitis. PMID- 26882060 TI - Assessing the Outcomes of Powered Endoscopic Dacryocystorhinostomy in Adults Using the Lacrimal Symptom (Lac-Q) Questionnaire. AB - PURPOSE: The objective of this study was to assess the quality of outcomes of powered endoscopic dacryocystorhinostomy using the lacrimal symptom (Lac-Q) questionnaire. METHODS: Prospective interventional case series of 50 consecutive patients who underwent primary powered endoscopic dacryocystorhinostomy were included in the study. All the patients had stent placement which were removed at 4 weeks. The Lac-Q questionnaire was administered preoperatively and at 4 weeks and 16 weeks following the surgery. Outcomes assessed were anatomical success, functional success, and changes in the social impact and lacrimal symptoms scores. Statistical analysis was performed using Dunnette's procedure with bonferroni correction. RESULTS: Fifty-five powered endoscopic dacryocysto rhinostomies were performed on 50 patients. A total of 150 questionnaire responses were analyzed. At the 16 week follow up, the anatomical and functional success rates were 98% and 94%, respectively. The mean social impact scores showed significant improvement postoperatively from 3.88 to 0.3 (p <= 0.001). The changes in the total scores (12.5 preoperatively to 1.0 at 16 weeks follow up) were statistically significant (p <= 0.001). Postoperative scoring correlated well with the anatomical and functional success rates. The symptom scores reflected changes with change in the clinical condition. CONCLUSION: The Lac-Q questionnaire is a simple and useful tool to evaluate the quality of outcomes of powered endoscopic dacryocystorhinostomy. PMID- 26882061 TI - Upper Eyelid and Pupillary Effects of Topical Dilute Epinephrine. AB - PURPOSE: Adrenergic medications may elevate the upper eyelid and dilate the pupil. The effects of topical phenylephrine on Muller's muscle have been well described. Dilute epinephrine (DE) is a sympathomimetic agent commonly administered in blepharoptosis surgery, and has been shown to elevate the upper eyelid margin when injected subcutaneously. The effects of DE applied topically to the eye, whether intentional or inadvertent during surgery have not been characterized. The purpose of this investigation was to quantify and compare the effects of topical DE and phenylephrine on upper eyelid position and pupil size. METHODS: Prospective, nonrandomized trial of 41 adults without (n = 25, 25 eyes) and with ptosis (n = 16, 16 eyes). Upper eyelid margin reflex distance (MRD1) and pupil diameter were primary measures and pupil reactivity to light was a secondary measure. MRD1 and pupil diameter were recorded at baseline and at 30 second intervals for 5 minutes after administration of topical 1% lidocaine with epinephrine 1:100,000 (DE). After a washout period of >24 hours, the same measurements were recorded after administration of topical phenylephrine 2.5%. RESULTS: No statistically significant difference was observed between mean baseline and postexposure MRD1 after application of topical DE (p = 0.181). In contrast, a mean increase in MRD1 of 0.51 +/- 0.09 mm (effect size 0.33) was observed after exposure to phenylephrine 2.5% (p < 0.001). Baseline-adjusted postexposure mean MRD1 was significantly greater for phenylephrine compared with DE (p < 0.001, analysis of covariance). Mean pupil diameter increased 0.29 +/- 0.09 mm (effect size 0.48) in response to DE and 0.27 +/- 0.11 mm (effect size 0.41) after application of phenylephrine (p = 0.004 and p = 0.001, respectively). All pupils maintained a constrictive response to light. CONCLUSIONS: Although DE is similar to topical phenylephrine in causing mydriasis, it did not have a similar effect on elevating the upper eyelid. These findings may have implications on intraoperative assessment during eyelid surgery. The pupillary changes due to DE offer one explanation for cases of transient pupil dilation during orbitofacial surgery. PMID- 26882062 TI - Comparative Study of Clinical, Pathological, Radiological, and Genetic Features of Patients With Adult Ocular Adnexal Xanthogranulomatous Disease, Erdheim Chester Disease, and IgG4-Related Disease of the Orbit/Ocular Adnexa. AB - PURPOSE: To compare and contrast the clinical, radiologic, pathologic, and genetic features of patients with ocular adnexal IgG4-related disease (IgG4-RD) and patients with adult ocular adnexal xanthogranulomatous disease (XG). METHODS: This retrospective review study identified patients with histological evidence of either disease from records of the pathology department of our hospital from 1996 to 2014. Clinical, imaging, and a variety of histopathologic features were collected for 23 patients with IgG4-RD and 13 patients with XG. Next generation sequencing with a 50-gene cancer screening panel was performed on biopsy tissues from 10 patients in each group. RESULTS: Statistical differences between the 2 groups include eyelid (67%; p = 0.0002) and anterior orbital (75%; p = 0.0352) predilection for XG except for Erdheim-Chester disease subgroup which was more posterior and diffuse. Eyelid involvement was rare (4%) for IgG4-RD. Involvement of orbital nerves was seen in 30% of IgG4-RD and 0% in XG (p = 0.0695). Five patients with IgG4-RD developed malignancy (4 lymphoma, 1 leiomyosarcoma), but none of XG patients. Discriminating pathological features were the presence of any IgG4+ plasma cells (p = 0.0121) and the ratio of IgG4+/IgG+ plasma cells (p =0.0294) for IgG4-RD. Five of 12 (42%) patients with XG had sufficient numbers of IgG4+ plasma cells/high power field to fulfill published diagnostic criteria for IgG4-RD, and 5 (42%) had a ratio of IgG4+/IgG+ plasma cells over 40%, but the numbers overall were less than seen in the IgG4-RD patients. The only genetic difference between the 2 groups was that BRAF V600E mutation was found in 1 of the 2 Erdheim-Chester disease patients, which form a subgroup of XG. CONCLUSIONS: IgG4-RD and XG share clinical, imaging, and histopathological features including IgG4+ plasma cells. Significant differences were the eyelid involvement in XG, orbital nerve involvement, and an elevated IgG4+/IgG+ ratio in IgG4-RD and the only genetic abnormality found was BRAF V600E mutation in the Erdheim-Chester disease subgroup of XG. PMID- 26882063 TI - Chemotherapy vs supportive care alone for relapsed gastric, gastroesophageal junction, and oesophageal adenocarcinoma: a meta-analysis of patient-level data. AB - BACKGROUND: Second-line chemotherapy treatment of patients with relapsed gastric and oesophageal cancers in comparison with supportive care (SC) alone has been supported by recent phase 3 clinical trials, but a meta-analysis of patient-level data is lacking. METHODS: We searched Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Web of Science for phase 3 clinical trials that compared second-line chemotherapy with SC alone for gastric and oesophageal cancers. A meta-analysis of the comprehensive patient-level data from the three identified trials was performed. RESULTS: A total of 410 patients with gastric (n=301), gastroesophageal junction (n=76), or oesophageal (n=33) adenocarcinoma were identified. In all, 154 patients received single-agent docetaxel and 84 patients received single-agent irinotecan, each with SC. SC alone was given to 172 patients. Chemotherapy significantly reduced the risk of death (hazard ratio (HR)=0.63, 95% confidence interval (CI)=0.51-0.77, P<0.0001). This effect was observed for treatment with docetaxel (HR=0.71, 95% CI=0.56-0.89, P=0.003) and irinotecan (HR=0.49, 95% CI=0.36-0.67, P<0.001). Overall survival (OS) benefit was greatest for patients who progressed 3-6 months following first-line chemotherapy (HR=0.39, 95% CI=0.26-0.59, P<0.0001). Performance status (PS) 0-1 compared with PS 2 (HR=0.66, 95% CI=0.46-0.94, P=0.02), locally advanced disease compared with metastatic disease (HR=0.41, 95% CI=0.25-0.67, P=0.0004) and older age (HR=0.94 per 5 years, 95% CI=0.90-0.99, P=0.01) were significant predictors of improved OS. Progression of disease during first-line treatment (HR=1.24, 95% CI=0.96-1.59) or within the first 3 months of completion of first-line treatment (HR=1.42, 95% CI=1.09-1.83) were predictors of an increased risk of death compared with progression between 3 and 6 months (P=0.03). Health-related quality of life outcomes were reported in only one of the three trials, precluding meta analysis of these parameters. CONCLUSIONS: This meta-analysis of patient-level data confirms that second-line chemotherapy treatment results in significantly better OS compared with SC alone in patients with platinum and fluoropyrimidine refractory gastric and oesphageal adenocarcinoma. Health-related quality of life outcomes should be included in future trials in this setting. PMID- 26882064 TI - Relationship between paediatric CT scans and subsequent risk of leukaemia and brain tumours: assessment of the impact of underlying conditions. AB - BACKGROUND: We previously reported evidence of a dose-response relationship between ionising-radiation exposure from paediatric computed tomography (CT) scans and the risk of leukaemia and brain tumours in a large UK cohort. Underlying unreported conditions could have introduced bias into these findings. METHODS: We collected and reviewed additional clinical information from radiology information systems (RIS) databases, underlying cause of death and pathology reports. We conducted sensitivity analyses excluding participants with cancer predisposing conditions or previous unreported cancers and compared the dose response analyses with our original results. RESULTS: We obtained information from the RIS and death certificates for about 40% of the cohort (n~180 000) and found cancer-predisposing conditions in 4 out of 74 leukaemia/myelodysplastic syndrome (MDS) cases and 13 out of 135 brain tumour cases. As these conditions were unrelated to CT exposure, exclusion of these participants did not alter the dose-response relationships. We found evidence of previous unreported cancers in 2 leukaemia/MDS cases, 7 brain tumour cases and 232 in non-cases. These previous cancers were related to increased number of CTs. Exclusion of these cancers reduced the excess relative risk per mGy by 15% from 0.036 to 0.033 for leukaemia/MDS (P-trend=0.02) and by 30% from 0.023 to 0.016 (P-trend<0.0001) for brain tumours. When we included pathology reports we had additional clinical information for 90% of the cases. Additional exclusions from these reports further reduced the risk estimates, but this sensitivity analysis may have underestimated risks as reports were only available for cases. CONCLUSIONS: Although there was evidence of some bias in our original risk estimates, re analysis of the cohort with additional clinical data still showed an increased cancer risk after low-dose radiation exposure from CT scans in young patients. PMID- 26882065 TI - Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer. AB - BACKGROUND: Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer. METHODS: CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis. RESULTS: Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1 mediated activation of Src was observed in cultured cells and mouse xenografts. CONCLUSIONS: CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer. PMID- 26882066 TI - Survivin and XIAP: two valuable biomarkers in medullary thyroid carcinoma. AB - BACKGROUND: Medullary thyroid carcinoma (MTC) accounts for ~5% of all thyroid malignancies. To date, surgery is the first-line therapy with curative intention. However, for advanced MTC, conventional chemotherapeutic agents do not provide convincing results. Therefore, the identification of biomarkers that can be antagonised by small-molecule therapeutics may lead to novel encouraging treatment options. METHODS: Seventy-nine patients with surgically resected and histologically confirmed MTC were included in this study. Tissue microarrays were constructed to assess the relationship between inhibitor of apoptosis proteins (IAPs) survivin or XIAP expression levels and clinicopathological variables as well as overall survival. RESULTS: High survivin or XIAP expression was associated with an advanced T-stage and metastatic disease. Whereas tissue expression levels of survivin correlated with serum calcitonin levels, XIAP was overexpressed in the subgroup of patients with sporadic MTC. Both IAPs were negatively associated with patient survival in the multivariate Cox regressions analysis (survivin: hazard ratio (HR) 1.62; 95% confidence interval (CI): 1.21 2.16; P=0.001; XIAP: HR 1.78; 95% CI: 1.16-2.72; P=0.008). CONCLUSIONS: Survivin and XIAP demonstrate distinct expression patterns in MTCs, which are associated with advanced disease and poor prognosis. We thus provide first evidence that both IAPs might serve as viable targets in patients with MTC. PMID- 26882068 TI - Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma. AB - BACKGROUND: Melanoma is a disease that primarily arises in the skin but is a derivative of the neural crest. Eukaryotic translation initiation factor 4E (eIF4E) regulates translation of multiple malignancy-associated mRNAs and is overexpressed in many epithelial tumours. However, expression in human tumours derived from the neural crest is unknown. Here, we determined the association of eIF4E and phospho-eIF4E expression in melanocytic lesions with malignant conversion, metastatic potential and patient survival. METHODS: Archived formalin fixed, paraffin-embedded surgical specimens from 114 patients with melanocytic lesions were stained immunohistochemically for eIF4E and phospho-eIF4E and evaluated semiquantitatively. The relationship between cytoplasmic and nuclear eIF4E and phospho-eIF4E protein expression, melanocytic lesion subtype and tumour progression was determined. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed. RESULTS: Increased eIF4E and phospho-eIF4E expression was highly associated with malignancy (P<0.0001). High nuclear phospho eIF4E was associated with synchronous or future metastasis (P=0.0059). Kaplan Meier analyses demonstrated highly significant associations between high histoscores for cytoplasmic and nuclear phospho-eIF4E and reduced survival in all patients (P=0.0003 and 0.0009, respectively). CONCLUSIONS: Increased melanoma expression of eIF4E and phospho-eIF4E is associated with metastatic potential, reduced survival and increased risk of death. PMID- 26882067 TI - Non-thermal atmospheric plasma induces ROS-independent cell death in U373MG glioma cells and augments the cytotoxicity of temozolomide. AB - BACKGROUND: Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG. METHODS: Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow cytometry and cytotoxicity assays. Fluorescent probes and inhibitors were used to determine the mechanisms of cytotoxicity of cells exposed to the plasma field. Combinational therapy with temozolomide (TMZ) and multi-dose treatments were explored as mechanisms to overcome resistance to NTAP. RESULTS: Non-thermal atmospheric plasma decreased cell viability in a dose (time)-dependent manner. U373MG cells were shown to be resistant to NTAP treatment when compared with HeLa cells, and the levels of intracellular reactive oxygen species (ROS) quantified in U373MG cells were much lower than in HeLa cells following exposure to the plasma field. Reactive oxygen species inhibitor N-acetyl cysteine (NAC) only alleviated the cytotoxic effects in HeLa cells and not in the relatively NTAP-resistant cell line U373MG. Longer exposures to NTAP induced a cell death independent of ROS, JNK and caspases in U373MG. The relative resistance of U373MG cells to NTAP could be overcome when used in combination with low concentrations of the GBM chemotherapy TMZ or exposure to multiple doses. CONCLUSIONS: For the very first time, we report that NTAP induces an ROS-, JNK- and caspase-independent mechanism of cell death in the U373MG GBM cell line that can be greatly enhanced when used in combination with low doses of TMZ. Further refinement of the technology may facilitate localised activation of cytotoxicity against GBM when used in combination with new and existing chemotherapeutic regimens. PMID- 26882069 TI - High level of interleukin-10 in serum predicts poor prognosis in multiple myeloma. AB - BACKGROUND: Interleukin-10 (IL-10) is a inhibiting inflammatory cytokine that plays an important role in immune suppressive microenvironment in multiple myeloma (MM). Whether the level of serum IL-10 could predict treatment response and survival outcomes or not needs to be investigated in MM patients. METHODS: The level of IL-10 in serum was measured using enzyme-linked immunosorbent assay in 188 patients with newly diagnosed MM. RESULTS: The best cutoff value for IL-10 in predicting survival is 169.69 pg ml(-1) with an area under the curve (AUC) value of 0.747 (P<0.001). In all, 92 patients (48.9%) were classified as high-IL 10 group (>169.96 pg ml(-1)) and 96 patients (51.1%) as low-IL-10 group (?169.96 pg ml(-1)). The overall response rate (ORR) was 79.2% in low-IL-10 group, significantly higher than that in high-IL-10 group (53.3%, P<0.001). Patients in low-IL-10 group had significantly better survival compared with those in high-IL 10 group (3-year PFS rate: 69.3% vs 13.3%, P<0.001; 3-year OS rate: 93.6% vs 51.9%, P<0.001). Multivariate analysis revealed that serum IL-10 level >169.96 pg ml(-1) at diagnosis and certain cytogenetic abnormalities were two adverse factors for PFS and OS. CONCLUSIONS: Our data suggest that serum IL-10 at diagnosis is a novel, powerful predictor of prognosis for MM. PMID- 26882070 TI - Lipoarabinomannan-Responsive Polycytotoxic T Cells Are Associated with Protection in Human Tuberculosis. AB - RATIONALE: The development of host-targeted, prophylactic, and therapeutic interventions against tuberculosis requires a better understanding of the immune mechanisms that determine the outcome of infection with Mycobacterium tuberculosis. OBJECTIVES: To identify T-cell-dependent mechanisms that are protective in tuberculosis. METHODS: Multicolor flow cytometry, cell sorting and growth inhibition assays were employed to compare the frequency, phenotype and function of T lymphocytes from bronchoalveolar lavage or the peripheral blood. MEASUREMENTS AND MAIN RESULTS: At two independent study sites, bronchoalveolar lavage cells from donors with latent tuberculosis infection limited the growth of virulent Mycobacterium tuberculosis more efficiently than those in patients who developed disease. Unconventional, glycolipid-responsive T cells contributed to reduced mycobacterial growth because antibodies to CD1b inhibited this effect by 55%. Lipoarabinomannan was the most potent mycobacterial lipid antigen (activation of 1.3% T lymphocytes) and activated CD1b-restricted T cells that limited bacterial growth. A subset of IFN-gamma-producing lipoarabinomannan responsive T cells coexpressed the cytotoxic molecules perforin, granulysin, and granzyme B, which we termed polycytotoxic T cells. Taking advantage of two well defined cohorts of subjects latently infected with Mycobacterium tuberculosis or patients who developed active disease after infection, we found a correlation between the frequency of polycytotoxic T cells and the ability to control infection (latent tuberculosis infection, 62%; posttuberculosis patients, 26%). CONCLUSIONS: Our data define an unconventional CD8(+) T-cell subset (polycytotoxic T cells) that is based on antigen recognition and function. The results link clinical and mechanistic evidence that glycolipid-responsive, polycytotoxic T cells contribute to protection against tuberculosis. PMID- 26882071 TI - The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products--A Study Using Aloin and Insulin. AB - Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major compounds in the solution were aloin A and aloin B. In addition, 10-hydroxy aloin and elgonica dimers were detected in smaller amounts. The identified compounds were isolated and tested for activity by means of Thioflavin T assays, but no activity was observed. Thus, the actual fibrillation inhibitor is an as yet unidentified and potentially metastable degradation product of aloin. These results suggest that degradation products, and in particular oxidation products, are to be considered thoroughly when natural products are investigated for activity against protein fibrillation. PMID- 26882073 TI - Registered report: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from 'RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth' by Hatzivassiliou and colleagues, published in Nature in 2010 (Hatzivassiliou et al., 2010). Hatzivassiliou and colleagues examined the paradoxical response of RAF-WT tumors to treatment with RAF inhibitors. The key experiments being replicated include Figure 1A, in which the original authors demonstrated that treatment of a subset of BRAF(WT) tumor cell lines with RAF small molecule inhibitors resulted in an increase in cell viability, Figure 2B, which reported that RAF inhibitor activation of the MAPK pathway was dependent on CRAF but not BRAF, and Figure 4A, where the dimerization of BRAF and CRAF was modulated by the RAF inhibitor PLX4720, but not GDC-0879. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. PMID- 26882074 TI - Review of Research Trends and Methods in Nano Environmental, Health, and Safety Risk Analysis. AB - Despite the many touted benefits of nanomaterials, concerns remain about their possible environmental, health, and safety (EHS) risks in terms of their toxicity, long-term accumulation effects, or dose-response relationships. The published studies on EHS risks of nanomaterials have increased significantly over the past decade and half, with most focused on nanotoxicology. Researchers are still learning about health consequences of nanomaterials and how to make environmentally responsible decisions regarding their production. This article characterizes the scientific literature on nano-EHS risk analysis to map the state-of-the-art developments in this field and chart guidance for the future directions. First, an analysis of keyword co-occurrence networks is investigated for nano-EHS literature published in the past decade to identify the intellectual turning points and research trends in nanorisk analysis studies. The exposure groups targeted in emerging nano-EHS studies are also assessed. System engineering methods for risk, safety, uncertainty, and system reliability analysis are reviewed, followed by detailed descriptions where applications of these methods are utilized to analyze nanomaterial EHS risks. Finally, the trends, methods, future directions, and opportunities of system engineering methods in nano-EHS research are discussed. The analysis of nano-EHS literature presented in this article provides important insights on risk assessment and risk management tools associated with nanotechnology, nanomanufacturing, and nano enabled products. PMID- 26882075 TI - Heavy metals in sediment and their accumulation in commonly consumed fish species in Bangladesh. AB - Six heavy metals (chromium [Cr], nickel [Ni], copper [Cu], arsenic [As], cadmium [Cd], and lead [Pb]) were measured in sediments and soft tissues of eleven commonly consumed fish species collected from an urban river in the northern part of Bangladesh. The abundance of heavy metals in sediments varied in the decreasing order of Cr > Ni > Cu > Pb > As > Cd. The ranges of mean metal concentrations in fish species, in mg/kg wet weight (ww), were as follows: Cr, 0.11-0.46; Ni, 0.77-2.6; Cu, 0.57-2.1; As, 0.43-1.7; Cd, 0.020-0.23; and Pb, 0.15 1.1. Target hazard quotients (THQs) and target carcinogenic risk (TR) showed the intake of As and Pb through fish consumption were higher than the recommended values, indicating the consumption of these fish species is associated with noncarcinogenic and carcinogenic health risks. PMID- 26882076 TI - Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. AB - IMPORTANCE: Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline. OBJECTIVE: To examine the association between the use of PPIs and the risk of incident dementia in the elderly. DESIGN, SETTING, AND PARTICIPANTS: We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015. EXPOSURES: Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole. MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy. RESULTS: A total of 73,679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70,729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001). CONCLUSIONS AND RELEVANCE: The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of beta-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail. PMID- 26882077 TI - The association between coffee consumption and bladder cancer incidence in a pooled analysis of the Miyagi Cohort Study and Ohsaki Cohort Study. AB - Recent epidemiological studies of the association between coffee consumption and the risk of bladder cancer have yielded conflicting results. The aim of the present study was to examine the association between coffee consumption and the incidence of bladder cancer on the basis of pooled data from two cohort studies carried out in Miyagi Prefecture, northeastern Japan. We delivered self administered questionnaires inquiring about the frequency of coffee consumption and other lifestyle factors in 1990 for the Miyagi Cohort Study and in 1994 for the Ohsaki Cohort Study. We followed 73 346 individuals from both cohorts and identified 274 cases of bladder cancer during 17.6 years for the Miyagi Cohort Study and 13.3 years for the Ohsaki Cohort Study. The multivariate-adjusted hazard ratios (95% confidence intervals) of bladder cancer incidence for the individuals who drank coffee occasionally, 1-2 cups/day, and 3 or more cups/day compared with never drinkers were 1.22 (0.90-1.66), 0.88 (0.61-1.26), and 0.56 (0.32-0.99), respectively (Ptrend=0.04). The inverse association remained even after stratification for smoking status. These data indicate that there is a significant inverse association between coffee consumption and the risk of bladder cancer. PMID- 26882079 TI - It is the examinee's IQ. AB - In response to the question "Whose IQ is it?" raised by McDermott, Watkins, and Rhoad (2014), this study examined the same concern about assessor bias by applying hierarchical linear modeling to a large and representative standardization sample of 2,200 child records in the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV). When differences in child age, gender, ethnicity, parental education level, and some intellectual abilities were cojointly used as covariates to adjust for nonrandom assignment problems, the results revealed that the Level 2 assessor variance was trivial for Full Scale IQ and all WISC-IV scores, ranging from 1%-5%, with the only exception being the Comprehension subtest, which showed a moderate level of between-assessor variance (10%). Evidence shows that WISC-IV scores are valid measures of children's intellectual abilities, with no evidence showing harmful assessor bias. (PsycINFO Database Record PMID- 26882078 TI - Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3. AB - OBJECTIVE: Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse. METHODS: Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression. RESULTS: An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P = 0.103 and P = 0.197, respectively). CONCLUSION: The association of an increase in PR3-ANCA level with the risk of subsequent relapse is partially affected by the PR3-ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3-ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3-ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy. PMID- 26882080 TI - A comparison of psychometric and convergent validity for social anhedonia and social closeness. AB - Social anhedonia is an important construct that describes individual differences in preferences for interacting in and experiencing pleasure from social interactions and has been a central construct in the schizotypy literature. The description of social anhedonia is very similar to that of social closeness from the personality literature. However, no published studies have directly compared associations between social anhedonia and social closeness with an array of other measures of anhedonia, personality, and depression. The present study examined the internal psychometrics of primary measures of social anhedonia and social closeness; the bivariate association between social anhedonia and social closeness; and the associations between these target constructs and measures of individual differences in a large sample of undergraduate students (mean age = 20.53 years; 76.3% were women). We found that (a) social anhedonia and social closeness were strongly correlated; (b) the unidimensional measurement model for social closeness was stronger than that for social anhedonia; (c) the pattern of associations for social closeness and social anhedonia with measures of physical anhedonia, personality, and depressive symptoms were substantively identical; and (d) a collection of items from both measures assessed information across a wider range of social anhedonia than either instrument alone. Thus, given the similar patterns of validity against multiple criteria social anhedonia and social closeness appear to be representing very similar constructs. The Social Closeness scale provides complementary information to the social anhedonia dimension. Our results provide recommendations for instrument selection when normative or elevated levels of social anhedonia are intended to be assessed. (PsycINFO Database Record PMID- 26882081 TI - Application of Dual Inhibition Concept within Looped Autoregulatory Systems toward Antivirulence Agents against Pseudomonas aeruginosa Infections. AB - Pseudomonas aeruginosa quorum-sensing (QS) is a sophisticated network of genome wide regulation triggered in response to population density. A major component is the self-inducing pseudomonas quinolone signal (PQS) QS system that regulates the production of several nonvital virulence- and biofilm-related determinants. Hence, QS circuitry is an attractive target for antivirulence agents with lowered resistance development potential and a good model to study the concept of polypharmacology in autoloop-regulated systems per se. Based on the finding that a combination of PqsR antagonist and PqsD inhibitor synergistically lowers pyocyanin, we have developed a dual-inhibitor compound of low molecular weight and high solubility that targets PQS transcriptional regulator (PqsR) and PqsD, a key enzyme in the biosynthesis of PQS-QS signal molecules (HHQ and PQS). In vitro, this compound markedly reduced virulence factor production and biofilm formation accompanied by a diminished content of extracellular DNA (eDNA). Additionally, coadministration with ciprofloxacin increased susceptibility of PA14 to antibiotic treatment under biofilm conditions. Finally, disruption of pathogenicity mechanisms was also assessed in vivo, with significantly increased survival of challenged larvae in a Galleria mellonella infection model. Favorable physicochemical properties and effects on virulence/biofilm establish a promising starting point for further optimization. In particular, the ability to address two targets of the PQS autoinduction cycle at the same time with a single compound holds great promise in achieving enhanced synergistic cellular effects while potentially lowering rates of resistance development. PMID- 26882084 TI - Study of the magnetite to maghemite transition using microwave permittivity and permeability measurements. AB - The microwave cavity perturbation (MCP) technique is used to identify the transition from magnetite (Fe3O4) to the meta-stable form of maghemite (gamma Fe2O3). In this study Fe3O4 was annealed at temperatures from 60 to 300 degrees C to vary the oxidation. Subsequent to annealing, the complex permittivity and magnetic permeability of the iron oxide powders were measured. The transition to gamma-Fe2O3 was corroborated with x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS) and vibrating sample magnetometry (VSM). XRD, XPS and VSM implied that the starting powder was consistent with Fe3O4 and the powders annealed at more than 200 degrees C were transitioning to gamma-Fe2O3. The MCP measurements gave large differences in both complex permittivity and magnetic permeability of the two phases in the frequency range of 2.5-10.2 GHz. Magnetic permeability decreased with annealing temperature, though magnetic losses showed frequency dependent behaviour. Complex permittivity measurements showed a large decrease in both dielectric constant and losses at all measurement frequencies, as well as a prominent loss peak centred around the phase transition temperatures. We interpret the loss peak as being a consequence of field effects due to an intermediate multi-phase mixture. Additionally, almost no frequency dependence was observed. The reduction in complex permittivity implies that the Feoct(2+) cations in the lattice provide a significant contribution to polarization at microwave frequencies and the effects of Feoct(3+) are nominal in comparison.. The change in loss can be explained as a combination of the differences in the effective conductivity of the two phases (i.e. Fe3O4 exhibits electron-hopping conduction whereas the presence of vacancies in gamma-Fe2O3 nullifies this). This shows that the non-invasive MCP measurements serve as a highly sensitive and versatile method for looking at this phase transition in iron and potentially the effects of oxidation states on the polarization in other iron oxides. PMID- 26882083 TI - Associations between Single-Nucleotide Polymorphisms in Corticotropin-Releasing Hormone-Related Genes and Irritable Bowel Syndrome. AB - Irritable bowel syndrome (IBS) is a common functional disorder with distinct features of stress-related pathophysiology. A key mediator of the stress response is corticotropin-releasing hormone (CRH). Although some candidate genes have been identified in stress-related disorders, few studies have examined CRH-related gene polymorphisms. Therefore, we tested our hypothesis that single-nucleotide polymorphisms (SNPs) in CRH-related genes influence the features of IBS. METHODS: In total, 253 individuals (123 men and 130 women) participated in this study. They comprised 111 IBS individuals and 142 healthy controls. The SNP genotypes in CRH (rs28364015 and rs6472258) and CRH-binding protein (CRH-BP) (rs10474485) were determined by direct sequencing and real-time polymerase chain reaction. The emotional states of the subjects were evaluated using the State-Trait Anxiety Inventory, Perceived Stress Scale, and the Self-rating Depression Scale. RESULTS: Direct sequencing of the rs28364015 SNP of CRH revealed no genetic variation among the study subjects. There was no difference in the genotype distributions and allele frequencies of rs6472258 and rs10474485 between IBS individuals and controls. However, IBS subjects with diarrhea symptoms without the rs10474485 A allele showed a significantly higher emotional state score than carriers. CONCLUSIONS: These results suggest that the CRH and CRH-BP genes have no direct effect on IBS status. However, the CRH-BP SNP rs10474485 has some effect on IBS related emotional abnormalities and resistance to psychosocial stress. PMID- 26882082 TI - Translation and Clinical Development of Antithrombotic Aptamers. AB - Thrombosis is a necessary physiological process to protect the body from uncontrolled bleeding. Pathological thrombus formation can lead to devastating clinical events including heart attack, stroke, deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. Numerous drugs have been developed to inhibit thrombosis. These have been targeted to coagulation factors along with proteins and receptors that activate platelets. While these drugs are effective at preventing blood clotting, their major side effect is inadvertent hemorrhage that can result in significant morbidity and mortality. There exists a need for anticoagulants that are not only effective at preventing thrombosis but can also be readily reversed. Aptamers offer a potential solution, representing a new class of drug agents that can be isolated to any protein and where antidote oligonucleotides can be designed based on the sequence of the aptamer. We present a summary of the anticoagulant and antithrombotic aptamers that have been identified and their stage of development and comment on the future of aptamer based drug development to treat thrombosis. PMID- 26882086 TI - Protein Fibrils Induce Emulsion Stabilization. AB - The behavior of an oil-in-water emulsion was studied in the presence of protein fibrils for a wide range of fibril concentrations by using rheology, diffusing wave spectroscopy, and confocal laser scanning microscopy. Results showed that above a minimum fibril concentration depletion flocculation occurred, leading to oil droplet aggregation and enhanced creaming of the emulsion. Upon further increasing the concentration of the protein fibrils, the emulsions were stabilized. In this stable regime both aggregates of droplets and single droplets are present, and these aggregates are smaller than the aggregates in the flocculated emulsion samples at the lower fibril concentrations. The size of the droplet aggregates in the stabilized emulsions is independent of fibril concentration. In addition, the droplet aggregation was reversible upon dilution both by a pH 2 HCl solution and by a fibril solution at the same concentration. The viscosity of the emulsions containing fibrils was comparable to that of the pure fibril solution. Neither fibril networks nor droplet gel networks were observed in our study. The stabilization mechanism of emulsions containing long protein fibrils at high protein fibril concentrations points toward the mechanism of a kinetic stabilization. PMID- 26882087 TI - Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review. AB - BACKGROUND: Body composition plays an important role in predicting treatment outcomes in adults with cancer. Using existing computed tomographic (CT) cross sectional imaging and readily available software, the assessment of skeletal muscle mass to evaluate sarcopenia has become simplified. We performed a systematic review and meta-analysis to quantify the prognostic value of skeletal muscle index (SMI) obtained from cross-sectional CT imaging on clinical outcomes in non-haematologic solid tumours. METHODS: We searched PubMed and the American Society Clinical Oncology online database of meeting abstracts up to October 2015 for relevant studies. We included studies assessing the prognostic impact of pre treatment SMI on clinical outcomes in patients with non-haematologic solid tumours. The primary outcome was overall survival (OS) and the secondary outcomes included cancer-specific survival (CSS), disease-free survival (DFS), and progression-free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. RESULTS: A total of 7843 patients from 38 studies were included. SMI lower than the cut-off was associated with poor OS (HR = 1.44, 95% CI = 1.32-1.56, p < 0.001). The effect of SMI on OS was observed among various tumour types and across disease stages. Worse CSS was also associated with low SMI (HR = 1.93, 95% CI = 1.38-2.70, p < 0.001) as well as DFS (HR = 1.16, 95% CI = 1.00-1.30, p = 0.014), but not PFS (HR = 1.54, 95% CI = 0.90-2.64, p = 0.117). CONCLUSIONS: This meta-analysis demonstrates that low SMI at cancer diagnosis is associated with worse survival in patients with solid tumours. Further research into understanding and mitigating the negative effects of sarcopenia in adults with cancer is needed. PMID- 26882088 TI - Catalytic Selenium-Promoted Intermolecular Friedel-Crafts Alkylation with Simple Alkenes. AB - A method for conducting selenium-promoted intermolecular Friedel-Crafts (F-C) alkylation reactions has been developed with simple alkenes using trimethylsilyl trifluoromethanesulfonate as a catalyst and N-phenylselenophthalimide as an efficient selenium source. Electron-rich arenes smoothly underwent F-C alkylation with a variety of alkenes to afford alkylated products in good yield and with high regioselectivity and diastereoselectivity. The regioselectivity and stereoselectivity of arenes and alkenes as well as a preliminary mechanism of the F-C alkylation reaction are discussed. PMID- 26882090 TI - The Effect of BAFF Inhibition on Autoreactive B-Cell Selection in Murine Systemic Lupus Erythematosus. AB - The goal of this study was to determine how B-cell-activating factor of the TNF family (BAFF) availability influences selection of the autoreactive B-cell repertoire in NZB/W and NZW/BXSB lupus-prone mice bearing the site-directed heavy chain transgene 3H9 that encodes for anti-dsDNA and anti-cardiolipin (CL) autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild-type cells and could be identified by green fluorescent protein. The light-chain repertoire associated with the 3H9 heavy chain in naive and antigen-activated B-cell subsets was assessed using single-cell polymerase chain reaction. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability, and there were only modest and physiologically non-relevant effects on the naive B-cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9-encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain, BAFF inhibition did not alter the selection of 3H9-encoded B cells in the germinal center, but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B-cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans. PMID- 26882091 TI - Enhanced Graphene Mechanical Properties through Ultrasmooth Copper Growth Substrates. AB - The combination of extraordinary strength and stiffness in conjunction with exceptional electronic and thermal properties in lightweight two-dimensional materials has propelled graphene research toward a wide array of applications including flexible electronics and functional structural components. Tailoring graphene's properties toward a selected application requires precise control of the atomic layer growth process, transfer, and postprocessing procedures. To date, the mechanical properties of graphene are largely controlled through postprocess defect engineering techniques. In this work, we demonstrate the role of varied catalytic surface morphologies on the tailorability of subsequent graphene film quality and breaking strength, providing a mechanism to tailor the physical, electrical, and mechanical properties at the growth stage. A new surface planarization methodology that results in over a 99% reduction in Cu surface roughness allows for smoothness parameters beyond that reported to date in literature and clearly demonstrates the role of Cu smoothness toward a decrease in the formation of bilayer graphene defects, altered domain sizes, monolayer graphene sheet resistance values down to 120 Omega/? and a 78% improvement in breaking strength. The combined electrical and mechanical enhancements achieved through this methodology allows for the direct growth of application quality flexible transparent conductive films with monolayer graphene. PMID- 26882089 TI - Multiple I-Type Lysozymes in the Hydrothermal Vent Mussel Bathymodiolus azoricus and Their Role in Symbiotic Plasticity. AB - The aim of this study was first to identify lysozymes paralogs in the deep sea mussel Bathymodiolus azoricus then to measure their relative expression or activity in different tissue or conditions. B. azoricus is a bivalve that lives close to hydrothermal chimney in the Mid-Atlantic Ridge (MAR). They harbour in specialized gill cells two types of endosymbiont (gram-bacteria): sulphide oxidizing bacteria (SOX) and methanotrophic bacteria (MOX). This association is thought to be ruled by specific mechanism or actors of regulation to deal with the presence of symbiont but these mechanisms are still poorly understood. Here, we focused on the implication of lysozyme, a bactericidal enzyme, in this endosymbiosis. The relative expression of Ba-lysozymes paralogs and the global anti-microbial activity, were measured in natural population (Lucky Strike--1700 m, Mid-Atlantic Ridge), and in in situ experimental conditions. B. azoricus individuals were moved away from the hydrothermal fluid to induce a loss of symbiont. Then after 6 days some mussels were brought back to the mussel bed to induce a re-acquisition of symbiotic bacteria. Results show the presence of 6 paralogs in B. azoricus. In absence of symbionts, 3 paralogs are up-regulated while others are not differentially expressed. Moreover the global activity of lysozyme is increasing with the loss of symbiont. All together these results suggest that lysozyme may play a crucial role in symbiont regulation. PMID- 26882092 TI - Lactic acidosis: relationship between metformin levels, lactate concentration and mortality. AB - AIM: The role of metformin in lactic acidosis is regularly questioned. Arguments against a causal role for metformin in lactic acidosis occurrence are the lack of correlation between plasma metformin and lactate levels, as well as between metformin plasma levels and mortality. We aim to analyse these correlations in a large series of lactic acidosis cases recorded in the French nationwide pharmacovigilance database. METHODS: All cases of lactic acidosis spontaneously reported between 1985 and October 2013 associated with metformin exposure were extracted from the pharmacovigilance database. We assessed the statistical correlations between prescribed daily doses of metformin, plasma concentrations of metformin and lactate, pH and plasma creatinine, as well as the relationship between mortality and these variables. RESULTS: Seven hundred and twenty-seven cases of lactic acidosis were reported during the period. Metformin plasma concentration was documented for 260 patients, lactate plasma concentration for 556 patients, pH for 502 patients, creatinine for 397 patients and the vital outcome for 713 patients. Metformin plasma concentration, lactate concentration, pH and plasma creatinine were all correlated (P < 0.001). There were significant differences between surviving and deceased patients in terms of metformin plasma levels (25.2 vs. 37.4 mg/l, P = 0.002) and lactate concentrations (10.8 vs. 16.3 mmol/l, P < 0.001). Thirty per cent of patients died when metformin concentration was > 5 mg/l compared with 11% for patients with concentration < 5 mg/l (P = 0.003). CONCLUSIONS: Our data suggest that metformin accumulation contributes to the pathogenesis and prognosis of lactic acidosis. PMID- 26882093 TI - The Use of Sound Level Meter Apps in the Clinical Setting. AB - PURPOSE: The purpose of this study was to compare sound level meter (SLM) readings obtained using a Larson-Davis (Depew, NY) Model 831 Type 1 SLM, a RadioShack (Fort Worth, TX) SLM, and iPhone 5 (Apple, Cupertino, CA) SLM apps. METHOD: In Procedure 1, pure tones were measured in an anechoic chamber (125, 250, 500, 1000, 2000, 4000, and 8000 Hz); sound pressure levels (SPLs) ranged from 60 to 100 dB SPL in 10-dB increments. In Procedure 2, human voices were measured. Participants were 20 vocally healthy adults (7 women, 13 men; mean age = 25.1 years). The task was to sustain a vowel "ah" at 3 intensity levels: soft, habitual, and loud. Microphones were lined up equal distances from the participant's mouth, and recordings were captured simultaneously. RESULTS: Overall, the 3 SLM apps and the RadioShack SLM yielded inconsistent readings compared with the Type 1 SLM. CONCLUSION: The use of apps for SPL readings in the clinical setting is premature because all 3 apps adopted were incomparable with the Type 1 SLM. PMID- 26882095 TI - Commensurability Effects in Viscosity of Nanoconfined Water. AB - The rate of water flow through hydrophobic nanocapillaries is greatly enhanced as compared to that expected from macroscopic hydrodynamics. This phenomenon is usually described in terms of a relatively large slip length, which is in turn defined by such microscopic properties as the friction between water and capillary surfaces and the viscosity of water. We show that the viscosity of water and, therefore, its flow rate are profoundly affected by the layered structure of confined water if the capillary size becomes less than 2 nm. To this end, we study the structure and dynamics of water confined between two parallel graphene layers using equilibrium molecular dynamics simulations. We find that the shear viscosity is not only greatly enhanced for subnanometer capillaries, but also exhibits large oscillations that originate from commensurability between the capillary size and the size of water molecules. Such oscillating behavior of viscosity and, consequently, the slip length should be taken into account in designing and studying graphene-based and similar membranes for desalination and filtration. PMID- 26882094 TI - Changes in Body Mass Related to the Initiation of Disease-Modifying Therapies in Rheumatoid Arthritis. AB - OBJECTIVE: Unintentional weight loss is important and can be predictive of long term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database. METHODS: Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m(2) . Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques. RESULTS: In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (beta = -0.41 kg/m(2) , 95% confidence interval [95% CI] -0.46, -0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (beta = 0.072 kg/m(2) , 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses. CONCLUSION: Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA. PMID- 26882096 TI - Prostate cancer patients' quality of life assessments across the primary treatment trajectory: 'True' change or response shift? AB - Background Self-report questionnaires are widely used to assess changes in quality of life (QoL) during the course of cancer treatment. However, comparing baseline scores to follow-up scores is only justified if patients' internal measurement standards have not changed over time, that is, no response shift occurred. We aimed to examine response shift in terms of reconceptualization, reprioritization and recalibration among prostate cancer patients. Material and methods We included 402 newly diagnosed patients (mean age 65 years) and assessed QoL at the beginning of cancer treatment and three months later. QoL was measured with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). We employed structural equation modeling testing measurement invariance between occasions to disentangle 'true' change and change in the measurement model (response shift). Results We found reprioritization effects for both the Physical Functioning and Role Functioning subscales of the EORTC QLQ-C30, indicating that both had gained importance for representing the latent construct of QoL at follow-up. These effects added to the worsening effect evident in the latent construct, thus rendering observed changes even more pronounced. In addition, we found recalibration effects for both the Emotional Functioning and Cognitive Functioning subscales indicating judgments becoming more lenient over time. These effects counteracted 'true' negative changes thus obscuring any substantial changes on the observed level. Conclusion Our results suggest that changes observed in some subscales of the EORTC QLQ-C30 should not be taken at face value as they may be affected by patients' changed measurement standards. PMID- 26882097 TI - The Very Long-Term Outcome of Radiosurgery for Classical Trigeminal Neuralgia. AB - BACKGROUND: Radiosurgery is one of the neurosurgical alternatives for intractable trigeminal neuralgia (TN). OBJECTIVE: Although acceptable short-/mid-term outcomes have been reported, long-term results have not been well documented. METHODS: We report the long-term results in 130 patients who underwent radiosurgery for classical TN and were subsequently monitored through at least 7 years (median = 9.9, range = 7-14.5) of follow-up. RESULTS: The median age was 66.5 years. A total of 122 patients (93.8%) became pain free (median delay = 15 days) after the radiosurgery procedure (Barrow Neurological Institute, BNI class I-IIIa). The probability of remaining pain free without medication at 3, 5, 7 and 10 years was 77.9, 73.8, 68 and 51.5%, respectively. Fifty-six patients (45.9%) who were initially pain free experienced recurrent pain (median delay = 73.1 months). However, at 10 years, of the initial 130 patients, 67.7% were free of any recurrence requiring new surgery (BNI class I-IIIa). The new hypesthesia rate was 20.8% (median delay of onset = 12 months), and only 1 patient (0.8%) reported very bothersome hypesthesia. CONCLUSIONS: The long-term results were comparable to those from our general series (recently published), and the high probability of long-lasting pain relief and rarity of consequential complications of radiosurgery may suggest it as a first- and/or second-line treatment for classical, drug-resistant TN. PMID- 26882098 TI - Functionalized Celluloses with Regular Substitution Pattern by Glycosynthase Catalyzed Polymerization. AB - Control of the monomer sequence in polymers is extraordinarily difficult by chemical synthesis, though Nature routinely exerts such control, including in the biosynthesis of polysaccharides. This inability has prevented us from being able to match the exquisite structure-activity control exhibited in biosynthesis of bioactive natural polysaccharides. We here address a powerful approach, whereby enzyme-catalyzed polymerization of properly modified building blocks is introduced as a simple route affording polysaccharides with controlled sequence and functionalization pattern. Targeting cellulose as a versatile scaffold for novel biomaterials, we describe the preparation of a perfectly alternating polysaccharide with repeat unit 6'-azido-6'-deoxycellobiose by a glycosynthase catalyzed polymerization using the Humicola insolens cellulase Cel7B E197A mutant, and its further functionalization to give novel modified cellulose derivatives with a regular substitution pattern. PMID- 26882099 TI - A Method to Pattern Silver Nanowires Directly on Wafer-Scale PDMS Substrate and Its Applications. AB - This study describes a fabrication method of microsized AgNW patterns based on poly dimethylsiloxane (PDMS) substrate using a poly(p-xylylene) (parylene) stencil technique. Various patterns of AgNW conductive sheets were created on the wafer scale area in the forms of straight and serpentine lines, texts, and symbols, which dimensions ranged from a few tens of micrometers to hundreds of micrometers. We demonstrated the electrical performance of straight line and serpentine line patterned AgNW electrodes when subjected to mechanical strains. The gauge factor and stretchability ranged from 0.5 to 55.2 at 2% uniaxial strain and from 4.7 to 55.7%, respectively, depending on the shapes and structures of the AgNW electrodes. Using the developed AgNW patterning technique, we fabricated strain sensors to detect small body signals epidermally such as hand motion, eye blink and heart rate. Also, tactile sensors were fabricated and exhibited the sensitivity of 3.91 MPa(-1) in the pressure range lower than 50 kPa, and 0.28 MPa(-1) in the pressure range greater than 50 kPa up to 1.3 MPa. From these results, we concluded that the proposed technique enables the fabrication of reliable AgNW patterns on wafer-scale PDMS substrate and the potential applications for various flexible electronic devices. PMID- 26882100 TI - Electronic Data Systems and Acute Kidney Injury. AB - Acute kidney injury (AKI) is a serious condition that is associated with an increased risk of death, long hospital stays, and high healthcare costs. The best chance of ameliorating the severity of AKI and improving its outcomes is through early recognition and intervention. Electronic health records (EHRs) have now become an integrated part of medical practice in most clinical settings worldwide. Appropriate use of EHRs potentially improves patient care, while poorly designed EHRs could result in unintended consequences. In recent years, EHRs with rule-based algorithms have been used for prompt AKI detection. Although studies using these systems have consistently shown that these EHRs have the capacity to improve the detection of AKI, their application in clinical practice to improve outcomes has shown conflicting results. Future use of EHRs for AKI should go beyond rule-based AKI detection to the creation of AKI-forecasting models for early identification of patients at high risk for AKI and the provision of clinical decision support systems to improve the quality of care and outcomes. Despite significant progress in the field of medical informatics and the growing use of EHRs to enhance the quality of care for AKI patients, these domains remain in the very early stages of development. In this chapter, we review the progress made in this field, as well as the methodologies, applications, and outcomes of using EHRs with AKI alerts. We also discuss the directions that EHR tools need to take to improve the care of patients with AKI. PMID- 26882101 TI - Native voice, self-concept and the moral case for personalized voice technology. AB - Purpose (1) To explore the role of native voice and effects of voice loss on self concept and identity, and survey the state of assistive voice technology; (2) to establish the moral case for developing personalized voice technology. Methods This narrative review examines published literature on the human significance of voice, the impact of voice loss on self-concept and identity, and the strengths and limitations of current voice technology. Based on the impact of voice loss on self and identity, and voice technology limitations, the moral case for personalized voice technology is developed. Results Given the richness of information conveyed by voice, loss of voice constrains expression of the self, but the full impact is poorly understood. Augmentative and alternative communication (AAC) devices facilitate communication but, despite advances in this field, voice output cannot yet express the unique nuances of individual voice. The ethical principles of autonomy, beneficence and equality of opportunity establish the moral responsibility to invest in accessible, cost effective, personalized voice technology. Conclusions Although further research is needed to elucidate the full effects of voice loss on self-concept, identity and social functioning, current understanding of the profoundly negative impact of voice loss establishes the moral case for developing personalized voice technology. Implications for Rehabilitation Rehabilitation of voice-disordered patients should facilitate self-expression, interpersonal connectedness and social/occupational participation. Proactive questioning about the psychological and social experiences of patients with voice loss is a valuable entry point for rehabilitation planning. Personalized voice technology would enhance sense of self, communicative participation and autonomy and promote shared healthcare decision-making. Further research is needed to identify the best strategies to preserve and strengthen identity and sense of self. PMID- 26882103 TI - Reply to a note on the magnitude of hazard ratios. PMID- 26882104 TI - Drone and Worker Brood Microclimates Are Regulated Differentially in Honey Bees, Apis mellifera. AB - BACKGROUND: Honey bee (Apis mellifera) drones and workers show differences in morphology, physiology, and behavior. Because the functions of drones are more related to colony reproduction, and those of workers relate to both survival and reproduction, we hypothesize that the microclimate for worker brood is more precisely regulated than that of drone brood. METHODOLOGY/PRINCIPAL FINDINGS: We assessed temperature and relative humidity (RH) inside honey bee colonies for both drone and worker brood throughout the three-stage development period, using digital HOBO(r) Data Loggers. The major findings of this study are that 1) both drone and worker castes show the highest temperature for eggs, followed by larvae and then pupae; 2) temperature in drones are maintained at higher precision (smaller variance) in drone eggs and larvae, but at a lower precision in pupae than the corresponding stages of workers; 3) RH regulation showed higher variance in drone than workers across all brood stages; and 4) RH regulation seems largely due to regulation by workers, as the contribution from empty honey combs are much smaller compared to that from adult workers. CONCLUSIONS/SIGNIFICANCE: We conclude that honey bee colonies maintain both temperature and humidity actively; that the microclimate for sealed drone brood is less precisely regulated than worker brood; and that combs with honey contribute very little to the increase of RH in honey bee colonies. These findings increase our understanding of microclimate regulation in honey bees and may have implications for beekeeping practices. PMID- 26882102 TI - Clinical Efficacy of Therapy with Recombinant Human Interferon alpha1b in Hand, Foot, and Mouth Disease with Enterovirus 71 Infection. AB - A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-alpha1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-alpha1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-14005153. PMID- 26882105 TI - The learning curve associated with anteromedial portal drilling in ACL reconstruction. AB - OBJECTIVES: The objective of the current study was to evaluate the accuracy and precision of femoral and tibial tunnel placement during anterior cruciate ligament reconstruction (ACLR) using independent anteromedial portal (AMP) drilling over a three-year observation period. METHODS: This study was a retrospective review of 161 consecutive primary ACL reconstructions from a single surgeon over his first 36-months in practice. Femoral and tibial tunnel angulation measurements were made on anteroposterior radiographs by a single observer utilizing the assessment method described by Aglietti et al. The accuracy and precision of tunnel placement across the three-year period were assessed with comparisons made. RESULTS: Significantly improved accuracy was demonstrated toward the cadaveric ideal femoral tunnel angle of 33.5 degrees over time. Improved precision of tunnel placement was also demonstrated evidenced by declining standard deviations across each year. Statistically significant improvement in femoral tunnel placement was seen between the first and second cohorts of 32 cases. No significant change was seen with respect to tibial tunnel angle across the observation period. CONCLUSIONS: A learning curve in developing accuracy and precision in ACL femoral tunnel placement using the AMP technique exists; our study indicates this to be somewhere between 32 and 64 cases. Tibial tunnel placement does not share the same learning curve using this surgical technique. PMID- 26882106 TI - Performance of Spot Photoscreener in Detecting Amblyopia Risk Factors in Chinese Pre-school and School Age Children Attending an Eye Clinic. AB - PURPOSE: To evaluate the effectiveness of Spot photoscreener in detecting amblyopia risk factors meeting 2013 the American Association of Pediatric Ophthalmology and Strabismus (AAPOS) criteria in Chinese preschool and school-age children. METHODS: One hundred and fifty-five children (310 eyes), aged between 4 to 7 years (5.74 +/- 1.2 years) underwent complete ophthalmologic examination, photoscreening, and cycloplegic retinoscopy refraction. The agreement of the results obtained with the photoscreening and retinoscopy was evaluated by linear regression and Bland-Altman plots. The sensitivity and specificity of detecting amblyopia risk factors were calculated based on the AAPOS 2013 guidelines. The overall effectiveness of detecting amblyopia risk factors was analyzed with Receiver Operating Characteristic (ROC) curves. RESULT: The mean refractive errors measured with the Spot were: spherical equivalent (SE) = 0.70 +/- 1.99 D, J0 = 0.87 +/- 1.01 D, J45 = 0.09 +/- 0.60 D. The mean results from retinoscopy were: SE = 1.19 +/- 2.22 D, J0 = 0.77 +/- 1.00 D, J45 = -0.02 +/- 0.45 D. There was a strong linear agreement between results obtained from those two methods (R2 = 0.88, P<0.01). Bland-Altman plot indicated a moderate agreement of cylinder values between the two methods. Based on the criteria specified by the AAPOS 2013 guidelines, the sensitivity and specificity (in respective order) for detecting hyperopia were 98.31% and 97.14%; for detecting myopia were 78.50% and 88.64%; for detecting astigmatism were 90.91% and 80.37%; for detecting anisometropia were 93.10% and 85.25%; and for detection of strabismus was 77.55% and 88.18%. CONCLUSION: The refractive values measured from Spot photoscreener showed a moderate agreement with the results from cycloplegic retinoscopy refraction, however there was an overall myopic shift of -0.49D. The performance in detecting individual amblyopia risk factors was satisfactory, but could be further improved by optimizing criteria based on ROC curves. PMID- 26882107 TI - Can KAATSU Exercise Cause Rhabdomyolysis? AB - In recent years, there has been increasing interest in using low-load resistance exercise in combination with a reduction in blood flow to promote muscle adaptation (ie, blood flow-restricted exercise or KAATSU exercise). There has been 1 case study reported in the literature of this type of exercise resulting in exertional rhabdomyolysis, and herein, we report the second case of exertional rhabdomyolysis. In this case, a 20-year-old man performed 6 sets of blood flow restricted exercise (3 sets of knee-extension and 3 sets of elbow-flexion exercise). The subject presented with high levels of delayed onset muscle soreness in the days after the exercise bout exhibited high levels of creatine kinase (peak recorded: 36 000 IU/L), and was hospitalized for exertional rhabdomyolysis. We urge that investigators and practitioners use caution with blood flow-restricted exercise protocols and to begin these exercise programs modestly and gradually progress them with time. PMID- 26882108 TI - Integration of Molecular Networking and In-Silico MS/MS Fragmentation for Natural Products Dereplication. AB - Dereplication represents a key step for rapidly identifying known secondary metabolites in complex biological matrices. In this context, liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) is increasingly used and, via untargeted data-dependent MS/MS experiments, massive amounts of detailed information on the chemical composition of crude extracts can be generated. An efficient exploitation of such data sets requires automated data treatment and access to dedicated fragmentation databases. Various novel bioinformatics approaches such as molecular networking (MN) and in-silico fragmentation tools have emerged recently and provide new perspective for early metabolite identification in natural products (NPs) research. Here we propose an innovative dereplication strategy based on the combination of MN with an extensive in-silico MS/MS fragmentation database of NPs. Using two case studies, we demonstrate that this combined approach offers a powerful tool to navigate through the chemistry of complex NPs extracts, dereplicate metabolites, and annotate analogues of database entries. PMID- 26882109 TI - Exploring Subclinical Phenotypic Features in Twin Pairs Discordant for Cleft Lip and Palate. AB - OBJECTIVE: Monozygotic twins of an individual with an orofacial cleft have a significantly elevated risk for orofacial cleft compared with the general population, but still the concordance rate for orofacial cleft in monozygotic twins is about 40% to 50%. The goal of this study was to determine whether unaffected cotwins have an increased frequency of orbicularis oris muscle defects, a subclinical form of orofacial cleft. The presence of such defects may reduce the overall rate of discordance. METHOD: A total of 63 discordant monozygotic and dizygotic twin pairs, 262 unaffected nontwin siblings, and 543 controls with no history of orofacial clefts were assessed for orbicularis oris defects by high-resolution ultrasound. Frequencies were compared by the Fisher exact test. RESULTS: Unaffected cotwins from discordant monozygotic pairs had a higher frequency of defects (12.5%) than the other test groups (6.38% to 6.99%), but the difference was not statistically significant (P = .74). CONCLUSIONS: In this study, orbicularis oris defects were not statistically significantly more common among the unaffected twins from orofacial cleft discordant twin pairs. The trends in the results warrant future studies with larger sample sizes and additional subclinical phenotypes. PMID- 26882110 TI - Exposure to Pre- and Perinatal Risk Factors Partially Explains Mean Differences in Self-Regulation between Races. AB - OBJECTIVES: To examine whether differential exposure to pre- and perinatal risk factors explained differences in levels of self-regulation between children of different races (White, Black, Hispanic, Asian, and Other). METHODS: Multiple regression models based on data from the Early Childhood Longitudinal Study, Birth Cohort (n ~ 9,850) were used to analyze the impact of pre- and perinatal risk factors on the development of self-regulation at age 2 years. RESULTS: Racial differences in levels of self-regulation were observed. Racial differences were also observed for 9 of the 12 pre-/perinatal risk factors. Multiple regression analyses revealed that a portion of the racial differences in self regulation was explained by differential exposure to several of the pre /perinatal risk factors. Specifically, maternal age at childbirth, gestational timing, and the family's socioeconomic status were significantly related to the child's level of self-regulation. These factors accounted for a statistically significant portion of the racial differences observed in self-regulation. CONCLUSIONS: The findings indicate racial differences in self-regulation may be, at least partially, explained by racial differences in exposure to pre- and perinatal risk factors. PMID- 26882111 TI - Comprehensive Geriatric Assessment and Transitional Care in Acutely Hospitalized Patients: The Transitional Care Bridge Randomized Clinical Trial. AB - IMPORTANCE: Older adults acutely hospitalized are at risk of disability. Trials on comprehensive geriatric assessment (CGA) and transitional care present inconsistent results. OBJECTIVE: To test whether an intervention of systematic CGA, followed by the transitional care bridge program, improved activities of daily living (ADLs) compared with systematic CGA alone. DESIGN, SETTING, AND PARTICIPANTS: This study was a double-blind, multicenter, randomized clinical trial conducted at 3 hospitals with affiliated home care organizations in the Netherlands between September 1, 2010, and March 1, 2014. In total, 1070 consecutive patients were eligible, 674 (63.0%) of whom enrolled. They were 65 years or older, acutely hospitalized to a medical ward for at least 48 hours with an Identification of Seniors at Risk-Hospitalized Patients score of 2 or higher, and randomized using permuted blocks stratified by study site and Mini-Mental State Examination score (<24 vs >=24). The dates of the analysis were June 1, 2014, to November 15, 2014. INTERVENTIONS: The transitional care bridge program intervention was started during hospitalization by a visit from a community care registered nurse (CCRN) and continued after discharge with home visits at 2 days and at 2, 6, 12, and 24 weeks. The CCRNs applied the CGA care and treatment plan. MAIN OUTCOMES AND MEASURES: The main outcome was the Katz Index of ADL at 6 months compared with 2 weeks before admission. Secondary outcomes were mortality, cognitive functioning, time to hospital readmission, and the time to discharge from a nursing home. RESULTS: The study cohort comprised 674 participants. Their mean age was 80 years, 42.1% (n = 284) were male, and 39.2% (n = 264) were cognitively impaired at admission. Intent-to-treat analysis found no differences in the mean Katz Index of ADL at 6 months between the intervention arm (mean, 2.0; 95% CI, 1.8-2.2) and the CGA-only arm (mean, 1.9; 95% CI, 1.7-2.2). For secondary outcomes, there were 85 deaths (25.2%) in the intervention arm and 104 deaths (30.9%) in the CGA-only arm, resulting in a lower risk on the time to death within 6 months after hospital admission (hazard ratio, 0.75; 95% CI, 0.56 0.99; P = .045; number needed to treat to prevent 1 death, 16). No other secondary outcome was significant. CONCLUSIONS AND RELEVANCE: A systematic CGA, followed by the transitional care bridge program, showed no effect on ADL functioning in acutely hospitalized older patients. TRIAL REGISTRATION: Netherlands Trial Registry: NTR2384. PMID- 26882113 TI - Farmer and Public Attitudes Toward Lamb Finishing Systems. AB - To develop research and policy on the welfare of lambs in intensive finishing systems, it is important to understand public and sheep farmers' attitudes. The aim of this research was to identify and compare farmer and community attitudes relevant to the intensification of lamb finishing. The majority of respondents in the community sample expressed concern about all listed welfare issues, but particularly about feedlotting of lambs and the associated confinement. These attitudes correlated with community views on the importance of welfare issues including social contact and freedom to roam. Farmers expressed much lower levels of concern than did the general public except with regard to the health of lambs, disease control, access to shade, and lack of access to clean water. PMID- 26882114 TI - Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon. AB - BACKGROUND/AIMS: Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. METHODS: The effects of neurotensin with concentrations ranging from 0.1-100 nM were studied in the intact rat colon in vitro, by investigating spatio temporal maps created from video recordings of colonic motility before and after neurotensin. RESULTS: Low concentration of neurotensin (0.1-1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction-- relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. CONCLUSIONS: Neurotensin (0.1-1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions. PMID- 26882115 TI - The Frequency of Huntington Disease and Huntington Disease-Like 2 in the South African Population. AB - BACKGROUND: Huntington disease (HD) has most recently been estimated to affect between 10.6 and 13.7 per 100,000 individuals in European populations. However, prevalence is known to differ geographically. In South Africa, the only published estimates are from a survey performed in the 1970s, an era when the disease was believed to be rare or absent in black individuals and molecular confirmation was absent. The disease phenotype in South Africa is currently attributable to mutations in both the huntington and junctophilin-3 genes, which underlie the well-known HD and the rarer HD-like 2 (HDL2) respectively. This study aimed at providing improved minimum estimates of disease frequency in South Africa, based on molecular genetic testing data. METHODS: A review of all testing records for HD and HDL2 over a 20-year period was undertaken. HDL2 is virtually indistinguishable on clinical features, thus necessitating its inclusion. RESULTS: Based on molecular diagnostic records, minimum estimates of disease frequency are: 5.1, 2.1 and 0.25 (per 100,000 individuals) for the white, mixed ancestry and black population groups respectively. CONCLUSION: Although ascertainment remains incomplete, these minimum estimates suggest that disease frequencies are significantly higher than those previously reported in South Africa. PMID- 26882112 TI - Impacts on Sirtuin Function and Bioavailability of the Dietary Bioactive Compound Dihydrocoumarin. AB - The plant secondary metabolite and common food additive dihydrocoumarin (DHC) is an inhibitor of the Sirtuin family of NAD+-dependent deacetylases. Sirtuins are key regulators of epigenetic processes that maintain silent chromatin in yeast and have been linked to gene expression, metabolism, apoptosis, tumorogenesis and age-related processes in multiple organisms, including humans. Here we report that exposure to the polyphenol DHC led to defects in several Sirtuin-regulated processes in budding yeast including the establishment and maintenance of Sir2p dependent silencing by causing disassembly of silent chromatin, Hst1p-dependent repression of meiotic-specific genes during the mitotic cell cycle. As both transient and prolonged exposure to environmental and dietary factors have the potential to lead to heritable alterations in epigenetic states and to modulate additional Sirtuin-dependent phenotypes, we examined the bioavailability and digestive stability of DHC using an in vivo rat model and in vitro digestive simulator. Our analyses revealed that DHC was unstable during digestion and could be converted to melilotic acid (MA), which also caused epigenetic defects, albeit less efficiently. Upon ingestion, DHC was observed primarily in intestinal tissues, but did not accumulate over time and was readily cleared from the animals. MA displayed a wider tissue distribution and, in contrast to DHC, was also detected in the blood plasma, interstitial fluid, and urine, implying that the conversion of DHC to the less bioactive compound, MA, occurred efficiently in vivo. PMID- 26882116 TI - Development of Itraconazole Liquisolid Compact: Effect of Polyvinylpyrrolidone on the Dissolution Properties. AB - The aim of this work was to utilize the liquisolid technique to enhance dissolution of itraconazole (ITZ). Liquisolid tablets of ITZ were formulated by using N-methyl-2-pyrrolidone as liquid vehicle, polyvinylpyrrolidone (PVP) as a precipitation inhibitor and magnesium aluminometasilicate Neusilin(r) as a carrier and coating material. The effect of PVP level on stability of liquid medication, physicomechnanical properties and dissolution rate of liquisolid compacts was studied in detail. The crystallinity of formulated drug and the interaction between excipients were examined by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). All the liquisolid tablets showed higher drug dissolution rates than the conventional, directly compressed tablets. The flowability of liquisolid powders was slightly improved as the proportion of PVP in ITZ-NMP mixture increased. Moreover, the stability of liquid medication and wetting ability of liquisolid tablets were improved by PVP. The presence of low amount of PVP (<= 1%) in liquisolid formulation could enhance dissolution of ITZ liquisolid tablets, whereas the percentage of PVP over 5% decreased the dissolution of ITZ from liquisolid tablets. Both DSC and XRPD suggested reduction or loss of ITZ crystallinity upon liquisolid formulations indicating that the drug was almost solubilized and molecularly dispersed with excipients within the liquisolid matrix. It could be shown that increased solubility, wetting properties and surface area available for dissolution contributed to the improvement of the dissolution of ITZ from liquisolid tablets. PMID- 26882117 TI - Intergenerational ambivalence in adolescence and early adulthood: Implications for depressive symptoms over time. AB - The parent-child relationship is often characterized by ambivalence, defined as the simultaneous experience of positive and negative relationship quality. This study examines reports of intergenerational ambivalence in 3 developmental periods: adolescence, emerging adulthood, and young adulthood, as well as its implications for depressive symptoms over a 12-year period. Participants ages 13 to 29 (n = 255) were interviewed in 1992 and again in 2005 at ages 25 to 41 (n = 186). Results indicate that offspring's reports of intergenerational ambivalence decreased over time. Greater ambivalence toward mothers predicted increased depressive symptoms over time while greater ambivalence toward fathers predicted decreased depressive symptoms over time. These results suggest that depressive symptoms in adulthood are vulnerable to the quality of the parent-child relationship earlier in the life course. (PsycINFO Database Record PMID- 26882119 TI - Development of the updating executive function: From 7-year-olds to young adults. AB - Updating information in working memory (WM) is a critical executive function responsible both for continuously replacing outdated information with new relevant data and to suppress or inhibit content that is no longer relevant according to task demands. The goal of the present research is twofold: First, we aimed to study updating development in 548 participants of 4 different age ranges -7-, 11-, and 15-year-olds and young adults--using the updating task devised by R. De Beni and P. Palladino (2004), which allows differentiating maintenance and inhibition processes. Second, we attempted to determine the relation between these processes across development as well as the differentiation among different types of inhibition processes tapped by this task. Results showed that there was an improvement of memory performance with age along with an upgrading of inhibitory efficiency. However, whereas in memory performance, a progressive increase was observed until the age of 15 years followed by stabilization, in inhibition, a continuous progressive increase was observed until young adulthood. Importantly, results showed that development of the different inhibitory mechanisms does not progress equally. All the groups committed more errors related to inefficient suppression mechanisms in WM than errors related to control of long-term memory interference. Principal component analysis showed that updating implies different subprocesses: active maintenance/suppression of information in WM and control of proactive interference. Developmental trajectories showed that the maintenance/suppression of information in the WM component continues to develop far beyond adolescence but that proactive interference control is responsible for variations in updating across development. PMID- 26882118 TI - A systems view of mother-infant face-to-face communication. AB - Principles of a dynamic, dyadic systems view of mother-infant face-to-face communication, which considers self- and interactive processes in relation to one another, were tested. The process of interaction across time in a large low-risk community sample at infant age 4 months was examined. Split-screen videotape was coded on a 1-s time base for communication modalities of attention, affect, orientation, touch, and composite facial-visual engagement. Time-series approaches generated self- and interactive contingency estimates in each modality. Evidence supporting the following principles was obtained: (a) Significant moment-to-moment predictability within each partner (self contingency) and between the partners (interactive contingency) characterizes mother-infant communication. (b) Interactive contingency is organized by a bidirectional, but asymmetrical, process: Maternal contingent coordination with infant is higher than infant contingent coordination with mother. (c) Self contingency organizes communication to a far greater extent than interactive contingency. (d) Self- and interactive contingency processes are not separate; each affects the other in communication modalities of facial affect, facial visual engagement, and orientation. Each person's self-organization exists in a dynamic, homoeostatic (negative feedback) balance with the degree to which the person coordinates with the partner. For example, those individuals who are less facially stable are likely to coordinate more strongly with the partner's facial affect and vice versa. Our findings support the concept that the dyad is a fundamental unit of analysis in the investigation of early interaction. Moreover, an individual's self-contingency is influenced by the way the individual coordinates with the partner. Our results imply that it is not appropriate to conceptualize interactive processes without simultaneously accounting for dynamically interrelated self-organizing processes. PMID- 26882121 TI - A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform. AB - Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for the role of the CYP3A5*3 polymorphism. The objective of this study was to identify genetic variants affecting the pharmacokinetics of tacrolimus using the DMETTM Plus microarray in 42 healthy males. Aside from CYP3A5*3, the rs3814055 polymorphism in the NR1I2 gene was associated with the tacrolimus pharmacokinetics based on false discovery rate corrected multiple tests and the least absolute shrinkage and selection operator analysis. The area under the concentration-time curve to the last quantifiable time point (AUClast) was 3.42 times greater in subjects with homozygous mutations in both genes (CYP3A5*3/*3 and NR1I2 T/T) than in wild-type subjects. The two variants explained the 54% variability in the tacrolimus AUClast. An in vitro luciferase reporter assay indicated that downregulation of PXR expression is the likely molecular mechanism responsible for the increased exposure to tacrolimus in subjects carrying the rs3814055 C>T variant. PMID- 26882120 TI - Up-Regulation of ENO1 by HIF-1alpha in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion. AB - PURPOSE: Alpha-enolase (ENO1), a major glycolytic enzyme, is reported to be over expressed in various cancer tissues. It has been demonstrated to be regulated by the Hypoxia-inducible factor 1-alpha (HIF-1alpha), a crucial transcriptional factor implicated in tumor progression and cancer angiogenesis. Choroidal neovascularization (CNV), which is a leading cause of severe vision loss caused by newly formed blood vessels in the choroid, is also engendered by hypoxic stress. In this report, we investigated the expression of ENO1 and the effects of its down-regulation upon cobalt (II) chloride-induced hypoxia in retinal pigment epithelial cells, identified as the primary source of ocular angiogenic factors. METHODS: HIF-1alpha-diminished retinal pigment epithelial cells were generated by small interfering RNA (siRNA) technology in ARPE-19 cells, a human retinal pigment epithelial cell line. Both normal and HIF-1alpha-diminished ARPE-19 cells were then subjected to hypoxic challenge using cobalt (II) chloride (CoCl2) or anaerobic chamber. The relation between ENO1 expression and vascular endothelial growth factor (VEGF) secretion by retinal pigment epithelial cells were examined. Protein levels of HIF-1alpha and ENO1 were analyzed using Western Blot, while VEGF secretion was essayed by enzyme-linked immunosorbent assay (ELISA). Cytotoxicity after hypoxia was detected by Lactate Dehydrogenase (LDH) Assay. RESULTS: Upon 24 hr of CoCl2-induced hypoxia, the expression levels of ENO1 and VEGF were increased along with HIF-1alpha in ARPE-19 cells, both of which can in turn be down-regulated by HIF-1alpha siRNA application. However, knockdown of ENO1 alone or together with HIF-1alpha did not help suppress VEGF secretion in hypoxic ARPE-19 cells. CONCLUSION: ENO1 was demonstrated to be up-regulated by HIF-1alpha in retinal pigment epithelial cells in response to hypoxia, without influencing VEGF secretion. PMID- 26882123 TI - Vulvar Lichen Sclerosus and Neoplastic Transformation: A Retrospective Study of 976 Cases. AB - OBJECTIVE: The aim of the study was to estimate the neoplastic potential of vulvar lichen sclerosus (VLS). MATERIALS AND METHODS: This was a retrospective study of 976 women with VLS. We recorded age at diagnosis of VLS, length of follow-up, and type of neoplasia, categorized as the following: (1) vulvar intraepithelial neoplasia (VIN), further subdivided in differentiated VIN (dVIN) and high-grade squamous intraepithelial lesion; (2) superficially invasive squamous cell carcinoma; and (3) frankly invasive squamous cell carcinoma. Neoplasia incidence risk, neoplasia incidence rate, and cumulative probability of progression to neoplasia according to the Kaplan-Meier method were estimated. Log rank test was used to compare the progression-free survival curves by age at diagnosis of VLS. RESULTS: The mean age at diagnosis of VLS was 60 (median = 60; range = 8-91) years. The mean length of follow-up was 52 (median = 21; range = 1 331) months. The following 34 patients developed a neoplasia: 8 VIN (4 dVIN, 4 high-grade squamous intraepithelial lesions), 6 keratinizing superficially invasive squamous cell carcinoma (5 with adjacent dVIN), and 20 keratinizing invasive squamous cell carcinoma (1 with adjacent dVIN). The neoplasia incidence risk was 3.5%. The neoplasia incidence rate was 8.1 per 1,000 person-years. The cumulative probability of progression to neoplasia increased from 1.2% at 24 months to 36.8% at 300 months. The median progression-free survival was significantly shorter in older women (>=70 years) when compared with that in younger women (p = .003). CONCLUSIONS: Vulvar lichen sclerosus has a nonnegligible risk of neoplastic transformation and requires a careful and lifelong follow-up in all patients, particularly in elderly women. Early clinical and histological detection of preinvasive lesions is essential to reduce the risk of vulvar cancer. PMID- 26882124 TI - Metastatic Genital Tract Adenocarcinoma to the Vulva: A Rare Occurrence Presenting as Painful Vulvar Enlargement. PMID- 26882122 TI - The effects of rosuvastatin on lipid-lowering, inflammatory, antioxidant and fibrinolytics blood biomarkers are influenced by Val16Ala superoxide dismutase manganese-dependent gene polymorphism. AB - Rosuvastatin is a cholesterol-lowering drug that also attenuates the inflammatory process and oxidative stress via the reduction of superoxide anion production. Superoxide anions are metabolized by manganese-dependent superoxide dismutase (MnSOD or SOD2) in the mitochondria. In humans, there is a gene polymorphism where a change of alanine (Ala) to valine (Val) occurs at the 16th amino acid (Ala16Val-SOD2). The VV genotype has been associated with the risk of developing several metabolic diseases, such as hypercholesterolemia. Thus, to further explore this phenomenon, this study investigated the influence of the Val16Ala SOD2 polymorphism on the lipid profile and inflammatory and fibrinolytic biomarkers of 122 hypercholesterolemic patients undergoing the first pharmacological cholesterol-lowering therapy who were treated with 20 mg rosuvastatin for 120 days. The findings indicate that the VV patients who present a low-efficiency SOD2 enzyme exhibit an attenuated response to rosuvastatin compared with the A-allele patients. The effect of rosuvastatin on inflammatory and fibrinolytic biomarkers was also less intense in the VV patients. These results suggest some pharmacogenetic effects of Val16Ala-SOD2 in hypercholesterolemia treatment. PMID- 26882125 TI - Surgical Treatment of Paget Disease of the Vulva: Prognostic Significance of Stromal Invasion and Surgical Margin Status. AB - OBJECTIVE: The aim of the study was to evaluate the risk of recurrence according to the surgical margin status and the presence of invasion or of superficially invasive carcinoma in patients with extramammary Paget disease (EMPD) of the vulva, who underwent elective surgical treatment. MATERIALS AND METHODS: We performed a retrospective analysis of 27 patients with first diagnosis of extramammary Paget disease of the vulva, who underwent primary and elective surgical treatment from January 1989 to December 2014. A p value of less than .05 was considered statistically significant. Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: We observed invasive disease in 11 cases, with microinvasion in 8 of them. A positive surgical margin was found in 10 patients. During a median follow-up period of 79.5 months, 8 patients (29.6%) showed a first recurrence after a median (range) time of 4.9 (2.3-7.1) years. No significant differences were observed between patients with recurrence and patients without recurrence with respect to age, number of vulvar sectors involved, bilaterality and multifocality, presence of invasion or microinvasion, and surgical margin status. However, during the follow-up period, the presence of invasion was higher (67% vs 41%) in patients with recurrence compared with patients without recurrence. CONCLUSIONS: The rate of recurrence of the disease after therapy is high. Patients should be subjected to a close and long-term follow-up to identify those who must undergo further treatment, especially if they presented with an invasive or even microinvasive disease. A free margin of no greater than 1 to 2 cm might be the most appropriate surgical choice. PMID- 26882126 TI - Toker Cells in an Erythematous Vulva From the Case Consultation Committee of the International Society for the Study of Vulvovaginal Disease. PMID- 26882127 TI - Simultaneous determination of corynoline and acetylcorynoline in human urine by LC-MS/MS and its application to a urinary excretion study. AB - Corynoline and acetycorynoline, the major active components derived from Corydalis bungeana Herba, showed multiple pharmacological activities. However, quantification of the two compounds in human urine has not been reported. A simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of corynoline and acetycorynoline in human urine has been developed and fully validated. The analytes were extracted from urine samples by simple liquid-liquid extraction. Chromatographic separation was achieved on a Hedera ODS-2C18 column with the mobile phase of water (containing 0.5% formic acid) and acetonitrile (28:72, v/v) at a flow rate of 0.4mL/min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring via an electrospray ionization source in positive mode. The monitored ion transitions were m/z 368.1->289.1 for corynoline, m/z 410.2->289.2 for acetycorynoline and m/z 380.2->243.2 for donepezil (internal standard), respectively. The calibration curves were linear (correlation coefficients>0.9970) over the concentration ranges of 3.0-3000pg/mL for corynoline and 3.0-1000pg/mL for acetycorynoline. The established method was highly sensitive with the lower limit of quantification (LLOQ) of 3.0pg/mL for both analytes. The intra- and inter-day precision was lower than 10% in terms of relative standard deviation for the low, medium, and high quality control samples, and lower than 16% for the LLOQ samples of the analytes. The accuracy was within +/-10% in terms of relative error for both analytes. The method was successfully applied to a urinary excretion study after oral administration of the Chinese medicine formula Shuanghua Baihe tablets in healthy volunteers. The urinary excretion profiles of corynoline and acetycorynoline in human were first reported. The results of this study suggest that renal excretion was not the main excretion pathway of corynoline and acetycorynoline in humans. PMID- 26882128 TI - Recognition and binding of beta-lactam antibiotics to bovine serum albumin by frontal affinity chromatography in combination with spectroscopy and molecular docking. AB - Serum albumins are the most abundant carrier proteins in blood plasma and participate in the binding and transportation of various exogenous and endogenous compounds in the body. This work was designed to investigate the recognition and binding of three typical beta-lactam antibiotics including penicillin G (Pen G), penicillin V (Pen V) and cefalexin (Cef) with bovine serum albumin (BSA) by frontal affinity chromatography in combination with UV-vis absorption spectra, fluorescence emission spectra, binding site marker competitive experiment and molecular docking under simulated physiological conditions. The results showed that a BSA only bound with one antibiotic molecule in the binding process, and the binding constants for Pen G-BSA, Pen V-BSA and Cef-BSA complexes were 4.22*10(1), 4.86*10(2) and 3.32*10(3) (L/mol), respectively. All the three beta lactam antibiotics were mainly inserted into the subdomain IIA (binding site 1) of BSA by hydrogen bonds and Van der Waals forces. The binding capacity between the antibiotics and BSA was closely related to the functional groups and flexibility of side chains in antibiotics. This study provided an important insight into the molecular recognition and binding interaction of BSA with beta lactam antibiotics, which may be a useful guideline for the innovative clinical medications and new antibiotic designs with effective pharmacological properties. PMID- 26882129 TI - Sepsis following cancer surgery: the need for early recognition and standardised clinical care. AB - Despite the implementation of multimodal bundles of care in hospitalised patients, post-operative sepsis in patients with cancer still accounts for a significant burden of illness and substantial healthcare costs. Patients undergoing surgery for cancer are at particular risk of sepsis due to underlying malignancy, being immunocompromised associated with cancer management and the complexity of surgical procedures performed. In this review, we evaluate the burden of illness and risks for sepsis following surgery for cancer. Current evidence supporting standardised strategies for sepsis management (including early recognition and resuscitation) is examined together with challenges in implementing quality improvement programs. PMID- 26882130 TI - Two Case Reports of Nodular Fasciitis: A Newly Recognized Placental Lesion. AB - We describe two occurrences of nontrophoblastic mesenchymal tumors of the placenta. The first placental tumor was found along the placental margin, and the second was identified close to the insertion of the fetal membranes along the placental disc. Microscopically both lesions demonstrated bland fibroblastic cells with intricate vasculature and inflammatory cells. Both lesions were negative for estrogen receptor (ER), progesterone receptor (PR), beta-HCG, PLAP, CD34, desmin, h-caldesmin, and smooth muscle actin by immunohistochemistry. Some cells were weakly positive for CD10, a nonspecific finding. The morphologic and immunohistochemical characteristics of these lesions were most consistent with nodular fasciitis, a tumor most commonly found in the soft tissues. FISH positive for USP6 gene rearrangement in our two patients confirmed the molecular similarity of these lesions to nodular fasciitis of soft tissue. Such lesions can be easily dismissed on gross placental examination as infarcts or thrombi, thus these rare entities are likely underreported. PMID- 26882131 TI - Isolation and identification of berberine and berberrubine metabolites by berberine-utilizing bacterium Rhodococcus sp. strain BD7100. AB - Based on the finding of a novel berberine (BBR)-utilizing bacterium, Rhodococcus sp. strain BD7100, we investigated the degradation of BBR and its analog berberrubine (BRU). Resting cells of BD7100 demethylenated BBR and BRU, yielding benzeneacetic acid analogs. Isolation of benzeneacetic acid analogs suggested that BD7100 degraded the isoquinoline ring of the protoberberine skeleton. This work represents the first report of cleavage of protoberberine skeleton by a microorganism. PMID- 26882132 TI - Hospitalists' utilization of weight loss resources with discharge texts and primary care contact: a feasibility study. AB - OBJECTIVES: Obesity affects a large proportion of the U.S. population, and hospitalizations may serve as an opportunity to promote weight loss. We sought to determine if multidisciplinary patient-centered inpatient weight loss intervention that included counseling, consults, post-discharge telephone text messages, and primary care follow up was feasible. METHODS: We conducted a feasibility study focusing on 25 obese hospitalized patients to understand the issues related to rolling out an intensive intervention. Actual weight loss was a secondary outcome and we compared these 25 patients to 28 control patients who were exposed to usual care; weight change was assessed at 1 and 6 months. RESULTS: Ninety-six percent (24/25) of nutritional consults and 92% (23/25) of physical therapy consults were submitted by hospital providers. All of these doctors were also reminded to counsel their patients about the detrimental health consequences. Fifty-two percent (13/25) and 40% (10/25) were actually seen and counseled by nutrition and physical therapy services respectively, before being discharged. Sixty-eight percent (17/25) received a motivational interviewing counseling session from the principal investigator. All patients were sent text messages and followed with their primary care provider after discharge who received the personalized weight loss discharge instructions that had been given to the patient. The feasibility group lost a mean of 3.0 kg at 6 months and the control group gained an average of 0.20 kg at 6 months post discharge (p = 0.03). CONCLUSION: Executing a multifaceted weight loss intervention for hospitalized obese patients is feasible, and there may be associated persistent improvements in weight status over time. PMID- 26882133 TI - [Factors of Influence on the Success of Rehabilitation]. PMID- 26882134 TI - [Emotion Recognition in Patients with Peripheral Facial Paralysis - A Pilot Study]. AB - BACKGROUND: The perception of emotions is an important component in enabling human beings to social interaction in everyday life. Thus, the ability to recognize the emotions of the other one's mime is a key prerequisite for this. OBJECTIVE: The following study aimed at evaluating the ability of subjects with 'peripheral facial paresis' to perceive emotions in healthy individuals. METHODS: A pilot study was conducted in which 13 people with 'peripheral facial paresis' participated. This assessment included the 'Facially Expressed Emotion Labeling Test' (FEEL-Test), the 'Facial-Laterality-Recognition Test' (FLR-Test) and the 'Toronto-Alexithymie-Scale 26' (TAS 26). The results were compared with data of healthy people from other studies. RESULTS: In contrast to healthy patients, the subjects with 'facial paresis' show more difficulties in recognizing basic emotions; however the results are not significant. The participants show a significant lower level of speed (right/left: p<0.001) concerning the perception of facial laterality compared to healthy people. With regard to the alexithymia, the tested group reveals significantly higher results (p<0.001) compared to the unimpaired people. CONCLUSIONS: The present pilot study does not prove any impact on this specific patient group's ability to recognize emotions and facial laterality. For future studies the research question should be verified in a larger sample size. PMID- 26882135 TI - [Adaptive Performance in Vocational Rehabilitation - A Standardized Self assessment Questionnaire (ReHadapt) for Application in RehaAssessment(r) and RehaConsulting]. AB - OBJECTIVES AND METHODS: A rehabilitation training requires the ability to adapt to a changed living and working environment. Qualitative content analysis and quantitative studies were conducted to (1(st)) provide a definition of adaptive performance (AP) in vocational rehabilitation. (2(nd)) A self-assessment questionnaire (ReHadapt) to measure AP was developed and (3(rd)) its validity was proved by the use of exploratory (N1=344) and confirmatory factor analysis (N2=301; N3=254) for categorical variables. RESULTS: AP is a multidimensional construct which can be assessed by the ReHadapt questionnaire. The ReHadapt questionnaire consists of 30 items which are categorized to the 6 dimensions training-related AP, subject-related AP, health-related AP, social AP towards other participants, social AP towards trainers and identification with future occupation. As expected, reliability (0,81<=Cronbach's Alpha<=0,95) and validity are confirmed. Adaptive Performance predicts return to work mediated by the health-related quality of life. IMPLICATIONS: Because of its economy and applicability in everyday work-life the ReHadapt can be used for diagnostic and training in RehaAssessment((r)) and RehaConsulting. PMID- 26882136 TI - [Progress of Rehabilitation for Cardiac Patients Depending on the Degree of Self Sufficiency at Admission]. AB - INTRODUCTION: There are hardly any publications about the outcome of cardiac rehabilitation considering patients with an increased need for medical, nursing and therapeutic care. The aim of this study, which consecutively included n=387 statutory health insurance inpatients over a period of 2 years, was to find out differences in outcome in self-care patients (Barthel index>70) as compared to patients with a need for complex care (Barthel index<=70). METHODS: Rehabilitation outcomes concerning physical capacity, emotional status and activities of daily living as measured by Barthel index, FIM index, HADS, clinical complications, exercise test, duration of rehabilitation and form of dismission were analyzed and compared between both groups. RESULTS: The inpatients with a Barthel index <=70 at admission were older, had a longer stay in hospital and in rehabilitation, developed more complications and more often suffered from concomitant diseases. They were readmitted to hospital more often. They showed a comparatively higher increase in indices of self-care and a significant increase in physical performance tests. CONCLUSION: Higher medical care expenses of multimorbid cardiac inpatients are no contraindication against rehabilitation, because even in this group the specific rehabilitation aims of the healthcare payers can be reached. PMID- 26882137 TI - [Structures and Practice of Psychological Services in Oncological and Diabetological Rehabilitation: Results of a Nationwide Survey]. AB - OBJECTIVE: To study the structural frame conditions and the contents of psychological activity in oncological rehabilitation as well as in rehabilitation of patients with type 2 diabetes. METHODS: We conducted a nationwide survey of psychological services in rehabilitation facilities treating oncological patients and patients with type 2 diabetes. RESULTS: 71 (of 145) oncological and 21 (of 63) diabetological rehabilitation facilities participated in the survey. In both indication areas an average of 1.1 psychologists is in charge of 100 patients. Between some rehabilitation facilities, however, there are considerable differences concerning the psychologist/patient ratio (in oncological rehabilitation facilities: standard deviation (SD)=0.52; in diabetological rehabilitation facilities: SD=0.35). Moreover, there is large heterogeneity among rehabilitation facilities as to the percentages of patients obtaining psychological interventions and the way in which psychological services allocate their working time. CONCLUSION: The general set-up of psychological services in oncological and diabetological rehabilitation facilities (especially the low psychologist/patient ratio in many facilities) can partly be considered insufficient. The heterogeneity with respect to the structural frame conditions and practice of psychological services reveals the low degree of standardization of psychological activity in both indication areas. PMID- 26882138 TI - [Implementation of Work-Related Medical Rehabilitation: A Propensity Score Matched Comparison of Two Cohorts from 2012 and 2014]. AB - AIM OF THE STUDY: We examined if the work-related treatment dose has changed in 2014 than compared to 2012, if the work-related treatment dose differed between common medical rehabilitation (MR) and work-related medical rehabilitation (WMR), and if the therapy recommendations for WMR were met in Northern Germany rehabilitation centres in 2014. MATERIAL AND METHODS: Patients who were treated in WMR or conventional medical rehabilitation in 2014 were matched with patients treated in 2012 by using propensity scores. RESULTS: Patients who were treated in WMR in 2014 received more work-related interventions than comparable patients in 2012 (13.5 vs. 2.5 h) and MR patients in 2014 (13.5 vs. 1.2 h). 30 min of social counselling, 180 min of work-related psychological groups and 360 min of work related functional capacity training were realised for 93.8, 82 and 41% of the patients participating in WMR in 2014 CONCLUSION: WMR programs in Northern Germany meet the recommendations of the WMR guideline. PMID- 26882139 TI - [Parkinsonian Syndromes: Direct Costs of Inpatient Neurological Rehabilitation]. AB - BACKGROUND: The Parkinsonian syndromes (PS) belong to the frequent chronic neurological disorders that, due to their progressive character and complex therapeutic options, pose a large economic burden. MATERIAL AND METHODS: In a retrospective health economic study on the treatment of Parkinson's disease, various socioeconomic and clinical parameters were examined. In the years 2011 2012, a total of 29 patients with the diagnosis of a Parkinsonian syndrome who underwent an inpatient rehabilitation in the Department of Neurology of the Rehabilitation MediClin Center Bad Orb were recruited. For this group of patients, we calculated the direct treatment cost and also analyzed the treatment cost based on the German diagnosis-related groups (G-DRG, version 2012). RESULTS: The direct medical costs amounted to ? 113.47+/-13.10 per patient per day. Furthermore, cost simulation and comparison revealed significantly higher cost per day for those patients insured via the German statutory health insurance who undergo inpatient care service based on the DRG-based payment (? 241.77 vs. 171.74; p<=0.015). CONCLUSION: This study contributes to the achievement of transparency of the direct medical costs of Parkinson's disease treatment in the inpatient setting and emphasizes the cost differences compared to the G-DRG-based payment. PMID- 26882140 TI - [Position Paper of the German Association for Rehabilitation: Remedies Enhance Self-Determined Participation]. PMID- 26882141 TI - [Update 2015 of the Working Group "Rehabilitation and Work" of the German Society for Rehabilitation Sciences]. PMID- 26882144 TI - Negative global phosphorus budgets challenge sustainable intensification of grasslands. AB - Grasslands provide grass and fodder to sustain the growing need for ruminant meat and milk. Soil nutrients in grasslands are removed through withdrawal in these livestock products and through animal manure that originates from grasslands and is spread in croplands. This leads to loss of soil fertility, because globally most grasslands receive no mineral fertilizer. Here we show that phosphorus (P) inputs (mineral and organic) in global grasslands will have to increase more than fourfold in 2050 relative to 2005 to achieve an anticipated 80% increase in grass production (for milk and meat), while maintaining the soil P status. Combined with requirements for cropland, we estimate that mineral P fertilizer use must double by 2050 to sustain future crop and grassland production. Our findings point to the need to better understand the role of grasslands and their soil P status and their importance for global food security. PMID- 26882150 TI - The invisible Hawley retainer. AB - This paper provides an overview of orthodontic retention. A clinical case is presented using the aesthetic Clearbow(r) to retain a hypodontia case prior to restorative replacement of a developmentally absent upper right lateral incisor tooth (UR2). CLINICAL RELEVANCE: Orthodontic retention is an important part of treatment. This is especially so in the treatment of multi-disciplinary hypodontia cases. The Clearbow(r), aesthetic labial bow provides superior aesthetics in comparison to conventional Hawley retainers. PMID- 26882145 TI - A new PK equivalence test for a bridging study. AB - In a bridging study, the plasma drug concentration-time curve is generally used to assess bioequivalence between the two formulations. Selected pharmacokinetic (PK) parameters including the area under the concentration-time curve, the maximum plasma concentration or peak exposure (Cmax), and drug half-life (T1/2) are compared to ensure comparable bioavailability of the two formulations. Comparability in these PK parameters, however, does not necessarily imply equivalence of the entire concentration-time profile. In this article, we propose an alternative metric of equivalence based on the maximum difference between PK profiles of the two formulations. A test procedure based on Bayesian analysis and accounting for uncertainties in model parameters is developed. Through both theoretical derivation and empirical simulation, it is shown that the new method provides better control over consumer's risk. PMID- 26882153 TI - British Orthodontic Society University Teachers Group Abstracts 2015. PMID- 26882157 TI - Corrigendum. AB - A modified occlusal wafer for managing partially dentate orthognathic patients - a case series. Bhavin Kiritkumar Soneji and Pratik Sharma. Vol 42, No. 1, pages 45-52. DOI 10.1179/1465313314Y.0000000115. The authors list for this paper should have read as: Bhavin Kiritkumar Soneji, Zaid Esmail and Pratik Sharma PMID- 26882158 TI - Erratum. AB - Orthodontic scanners: what's available? Catherine B. Martin, Elsinore V. Chalmers, Grant T. McIntyre, Heather Cochrane and Peter A. Mossey Vol 42, No. 2, pages 136-144. 10.1179/1465313315Y.0000000001. The second author's name was misreproduced and should have read: Elinor V. Chalmers. PMID- 26882159 TI - As time goes by. PMID- 26882162 TI - Erratum. PMID- 26882161 TI - Platelet type von Willebrand disease and registry report: communication from the SSC of the ISTH. PMID- 26882163 TI - Acute Respiratory Distress Syndrome in Lung Paracoccidioidomycosis. PMID- 26882164 TI - Effect of heavy metals on seed germination and seedling growth of common ragweed and roadside ground cover legumes. AB - In southern Quebec, supplement roadside ground covers (i.e. Trifolium spp.) struggle to establish near edges of major roads and thus fail to assist turf recruitment. It creates empty niches vulnerable to weed establishment such as common ragweed (Ambrosia artemisiifolia). We hypothesized that heavy metal stresses may drive such species shifts along roadside edges. A growth chamber experiment was conducted to assess effects of metals (Zn, Pb, Ni, Cu, and Cd) on germination and seedling behaviors of roadside weed (A. artemisiifolia) and ground cover legumes (Coronilla varia, Lotus corniculatus, and Trifolium arvense). All metals inhibited T. arvense germination, but the effect was least on A. artemisiifolia. Low levels of Pb and Ni promoted germination initiation of A. artemisiifolia. Germination of L. corniculatus was not affected by Zn, Pb, and Ni, but inhibited by Cu and Cd. Germination of C. varia was decreased by Ni, Cu, and Cd and delayed by Zn and Pb. Metal additions hindered seedling growth of all test species, and the inhibitory effect on the belowground growth was greater than on the aboveground growth. Seedling mortality was lowest in A. artemisiifolia but highest in T. arvense when exposed to the metal treatments. L. corniculatus and C. varia seedlings survived when subjected to high levels of Zn, Pb, and Cd. In conclusion, the successful establishment of A. artemisiifolia along roadside edges can be associated with its greater tolerance of heavy metals. The findings also revealed that L. corniculatus is a potential candidate for supplement ground cover in metal-contaminated roadside edges in southern Quebec, especially sites contaminated with Zn and Pb. PMID- 26882168 TI - Understanding Local Policy Elites' Perceptions on the Benefits and Risks Associated with High-Voltage Power Line Installations in the State of Arkansas. AB - Recently, a controversial policy debate has arisen concerning the installation of high-voltage power lines in northwest Arkansas. While proponents argue that such an installation is inevitable to efficiently and reliably support the identified electric load in the region, opponents claim that the lines will degrade the natural environment and hamper the tourism-based local economy in affected regions, notably in Ozark Mountain areas. Of particular interest is to understand how local policy elites perceive the benefits and risks associated with such divisive proposals, which is critical for comprehending the formation and changes of related government policies. Based upon the dual process theory of judgment, this study systematically investigates the triadic relationships between (a) more profound personal value predispositions, (b) affects and feelings, and (c) perceived benefits and risks related to the proposed installation of high-voltage power lines among local policy elites in the state of Arkansas. In doing so, we analyze original data collected from a statewide Internet survey of 420 local leaders and key policymakers about their opinions on the related issues, while considering other factors claimed by previous literature to influence risk perceptions, including trust, knowledge level, and demographic characteristics. Analytical results suggest that grid-group cultural predispositions, as deeply held core values within local policy elites' individual belief systems, both directly and indirectly-through affective feelings-shape perceived utility associated with the installation of high-voltage power lines. We conclude this article by suggesting some practical considerations for better designing policy addressing controversial issues of this nature. PMID- 26882165 TI - Severe Enterovirus Infections in Hospitalized Children in the South of England: Clinical Phenotypes and Causative Genotypes. AB - BACKGROUND: Most enterovirus surveillance studies lack detailed clinical data, which limits their clinical usefulness. This study aimed to describe the clinical spectrum and outcome of severe enterovirus infections in children, and to determine whether there are associations between causative enterovirus genotypes and clinical phenotypes. METHODS: Retrospective analysis of microbiological and clinical data from a tertiary children's hospital in the South of England over a 17-month period (2012-2013). RESULTS: In total, 30 patients were identified, comprising sepsis (n = 9), myocarditis (n = 8), meningitis (n = 8) and encephalitis (n = 5). Cases with sepsis or myocarditis were significantly younger than those with central nervous system disease (median age 21 and 15 days vs. 79 days; P = 0.0244 and P = 0.0310, respectively). There was considerable diversity in the causative genotypes in each of the clinical phenotypes, with some predominance of echoviruses in the meningitis group, and coxsackie B viruses in the myocarditis group. Thirteen cases required mechanical ventilation, 11 cases inotropic support, 3 cases dialysis and 3 cases extracorporal membrane oxygenation. The overall mortality was 10% (sepsis group, n = 1; myocarditis group, n = 2). Of the survivors, 5 (19%) had long-term sequelae (myocardial dysfunction, n = 2; neurological sequelae, n = 3). Patients with encephalitis had the longest hospital stay (median: 16 days), compared with 9, 6 and 3 days in patients with myocarditis, sepsis and meningitis, respectively (P = 0.005). CONCLUSIONS: Enterovirus infections, particularly enteroviral myocarditis and encephalitis, can cause significant morbidity and mortality. The results show that there are currently no strong associations between clinical phenotypes and particular causative enterovirus genotypes in the South of England. PMID- 26882170 TI - Autism Screening or Smoke Screen and Mirrors? PMID- 26882169 TI - Inter-Protein Sequence Co-Evolution Predicts Known Physical Interactions in Bacterial Ribosomes and the Trp Operon. AB - Interaction between proteins is a fundamental mechanism that underlies virtually all biological processes. Many important interactions are conserved across a large variety of species. The need to maintain interaction leads to a high degree of co-evolution between residues in the interface between partner proteins. The inference of protein-protein interaction networks from the rapidly growing sequence databases is one of the most formidable tasks in systems biology today. We propose here a novel approach based on the Direct-Coupling Analysis of the co evolution between inter-protein residue pairs. We use ribosomal and trp operon proteins as test cases: For the small resp. large ribosomal subunit our approach predicts protein-interaction partners at a true-positive rate of 70% resp. 90% within the first 10 predictions, with areas of 0.69 resp. 0.81 under the ROC curves for all predictions. In the trp operon, it assigns the two largest interaction scores to the only two interactions experimentally known. On the level of residue interactions we show that for both the small and the large ribosomal subunit our approach predicts interacting residues in the system with a true positive rate of 60% and 85% in the first 20 predictions. We use artificial data to show that the performance of our approach depends crucially on the size of the joint multiple sequence alignments and analyze how many sequences would be necessary for a perfect prediction if the sequences were sampled from the same model that we use for prediction. Given the performance of our approach on the test data we speculate that it can be used to detect new interactions, especially in the light of the rapid growth of available sequence data. PMID- 26882171 TI - Comprehensive epidemiological and genotype-phenotype analyses in a large European sample with idiopathic achalasia. AB - BACKGROUND AND AIM: Although an eight-residue insertion in HLA-DQbeta1 has been recently identified as a genetic risk factor for idiopathic achalasia, other risk factors are still unknown. In the present study, we carried out an epidemiological survey and a genotype-phenotype (G*P) analysis to gain further insights into the etiology of achalasia. METHODS: We obtained medical data from 696 achalasia patients and 410 controls, as well as their first-degree relatives (2543 of patients and 1497 of controls). For the G*P analysis, we stratified the patients into HLA-DQbeta1 insertion carriers and noncarriers. RESULTS: Our data show that patients are more often affected by viral infections before achalasia onset (P<0.0001, most significantly for varicella zoster virus infections). In addition, allergic (P=0.0005) and autoimmune disorders (P=0.0007, most significantly for psoriasis and Sjogren's syndrome) represent comorbid disease conditions. First-degree relatives of patients also show higher prevalence rates of allergic disorders (P=0.0007) and psoriasis (P=0.016) compared with control relatives. Moreover, the G*P analysis reveals that achalasia is triggered by pregnancies in female HLA-DQbeta1 insertion carriers (P=0.031). CONCLUSION: Our data point to a role of viral infections in the development of achalasia. In addition, they provide evidence for a relationship between achalasia and allergic, as well as autoimmune, disorders. Furthermore, pregnancy seems to be a disease-triggering factor in female HLA-DQbeta1 insertion carriers, which points to hormonal and/or immunosuppressive factors influencing disease development. PMID- 26882172 TI - Supplementation of ursodeoxycholic acid improves fat digestion and absorption in cystic fibrosis patients with mild liver involvement. AB - BACKGROUND: Ursodeoxycholic acid (UDCA) supplementation is recommended for cystic fibrosis (CF) patients with associated liver disease. However, its effect on fat digestion and absorption is not known. MATERIALS AND METHODS: In 23 patients with mild liver involvement, a C-mixed triglyceride breath test was performed on UDCA supplementation (with and without pancreatic enzymes - standard and increased dose) and after 1 month of UDCA withdrawal. Cumulative percentage dose recovery [CPDR; median (interquartile range)] has been considered to reflect lipid digestion and absorption. RESULTS: The enzyme supplementation resulted in a significant CPDR improvement [0% (0-0) vs. 4.6% (0.4-6.0); P<0.00046]. With the increased dose of enzymes in 16 patients with abnormal C-mixed triglyceride breath test results and lipase dose less than 3000 U/g of fat, higher CPDR values [8.6% (5.6-12.7); P<0.000027] were observed. However, a 1-month UDCA withdrawal resulted in a significant reduction in (P<0.000031) fat digestion and absorption [2.9% (0.7-5.8)]. CONCLUSION: UDCA supplementation seems to enhance lipid digestion and absorption in pancreatic insufficient CF patients with mild liver involvement. This finding points toward the potential impact of UDCA supplementation on nutritional status in CF patients with liver disease and underscores the often overlooked role of factors other than pancreatic enzymes on digestion and absorption of fats in CF. PMID- 26882173 TI - A Point-of-Care Raman Spectroscopy-Based Device for the Diagnosis of Gout and Pseudogout: Comparison With the Clinical Standard Microscopy. AB - OBJECTIVE: To demonstrate the usefulness of a novel medical device based on Raman spectroscopy for the rapid point-of-care diagnosis of gout and pseudogout. METHODS: A shoebox-sized point-of-care Raman spectroscopy (POCRS) device was developed for use in the diagnosis of gout and pseudogout. The device included a disposable syringe microfiltration kit to collect arthropathic crystals from synovial fluid and a customized automated Raman spectroscopy system to chemically identify crystal species. Diagnosis according to the findings of POCRS was compared with the clinical standard diagnosis based on compensated polarized light microscopy (CPLM) of synovial fluid aspirates collected from symptomatic patients (n = 174). Kappa coefficients were used to measure the agreement between POCRS and CPLM findings. RESULTS: Overall, POCRS and CPLM results were consistent in 89.7% of samples (156 of 174). For the diagnosis of gout, the kappa coefficient for POCRS and CPLM was 0.84 (95% confidence interval [95% CI] 0.75 0.94). For the diagnosis of pseudogout, the kappa coefficient for POCRS and CPLM was 0.61 (95% CI 0.42-0.81). CONCLUSION: Kappa coefficients indicated that there was excellent agreement between POCRS and CPLM for the diagnosis of gout, with good agreement for the diagnosis of pseudogout. The POCRS device holds the potential to standardize and expedite the time to clinical diagnosis of gout and pseudogout, especially in settings where certified operators trained for CPLM analysis are not available. PMID- 26882174 TI - Uncharged nucleoside inhibitors of beta-1,4-galactosyltransferase with activity in cells. AB - We report 5-substituted uridine derivatives as novel, uncharged inhibitors of beta-1,4-galactosyltransferase and chemical tools for cellular applications. The new inhibitors reduce P-selectin glycoprotein 1 (PSGL-1) expression in human monocytes. Our results also provide novel insights into a unique mode of glycosyltransferase inhibition. PMID- 26882175 TI - Imaging Pseudomonas aeruginosa Biofilm Extracellular Polymer Scaffolds with Amphiphilic Carbon Dots. AB - Biofilm formation is a critical facet of pathogenesis and resilience of human, animal, and plant bacteria. Extracellular polymeric substances (EPS) constitute the physical scaffolding for bacterial biofilms and thus play central roles in their development and virulence. We show that newly synthesized amphiphilic fluorescent carbon dots (C-dots) readily bind to the EPS scaffold of Pseudomonas aeruginosa, a major biofilm-forming pathogen, resulting in unprecedented microscopic visualization of the EPS structural features. Fluorescence microscopy analysis utilizing the C-dots reveals that the P. aeruginosa EPS matrix exhibits a remarkable dendritic morphology. The experiments further illuminate the growth kinetics of the EPS and the effect of external factors such as temperature. We also show that the amphiphilic C-dot platform enabled screening of substances disrupting biofilm development, specifically quorum sensing inhibitors. PMID- 26882176 TI - Sex and HIV serostatus differences in decision making under risk among substance dependent individuals. AB - HIV+ individuals with and without substance use disorders make significantly poorer decisions when information about the probability and magnitude of wins and losses is not available. We administered the Game of Dice Task, a measure of decision making under risk that provides this information explicitly, to 92 HIV+ and 134 HIV- substance-dependent men and women. HIV+ participants made significantly poorer decisions than HIV- participants, but this deficit appeared more prominent among HIV+ women. These data indicate that decision making under risk is impaired among HIV+ substance-dependent individuals (SDIs). Potential factors for the HIV+ women's relatively greater impairment are discussed. PMID- 26882177 TI - The role of attention in emotional memory enhancement in pathological and healthy aging. AB - After short delays between encoding and retrieval, healthy young participants have better memory performance for emotional stimuli than for neutral stimuli. Divided-attention paradigms suggest that this emotional enhancement of memory (EEM) is due to different attention mechanisms involved during encoding: automatic processing for negative stimuli, and controlled processing for positive stimuli. As far as we know, no study on the influence of these factors on EEM in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients, as compared to healthy young and older controls, has been conducted. Thus, the goal of our study was to ascertain whether the EEM in these populations depends on the attention resources available at encoding. Participants completed two encoding phases: full attention (FA) and divided attention (DA), followed by two retrieval phases (recognition tasks). There was no EEM on the discrimination accuracy, independently of group and encoding condition. Nevertheless, all participants used a more liberal response criterion for the negative and positive stimuli than for neutral ones. In AD patients, larger numbers of false recognitions for negative and positive stimuli than for neutral ones were observed after both encoding conditions. In MCI patients and in healthy older and younger controls this effect was observed only for negative stimuli, and it depended on the encoding condition. Thus, this effect was observed in young controls after both encoding conditions, in older controls after the DA encoding, and in MCI patients after the FA encoding. In conclusion, our results suggest that emotional valence does not always enhance discrimination accuracy. Nevertheless, in certain conditions related to the attention resources available at encoding, emotional valence, especially the negative one, enhances the subjective feeling of familiarity and, consequently, engenders changes in response bias. This effect seems to be sensitive to the age and the pathology of participants. PMID- 26882178 TI - Indicators of suboptimal performance embedded in the Wechsler Memory Scale-Fourth Edition (WMS-IV). AB - INTRODUCTION: Recognition and visual working memory tasks from the Wechsler Memory Scale-Fourth Edition (WMS-IV) have previously been documented as useful indicators for suboptimal performance. The present study examined the clinical utility of the Dutch version of the WMS-IV (WMS-IV-NL) for the identification of suboptimal performance using an analogue study design. METHOD: The patient group consisted of 59 mixed-etiology patients; the experimental malingerers were 50 healthy individuals who were asked to simulate cognitive impairment as a result of a traumatic brain injury; the last group consisted of 50 healthy controls who were instructed to put forth full effort. RESULTS: Experimental malingerers performed significantly lower on all WMS-IV-NL tasks than did the patients and healthy controls. A binary logistic regression analysis was performed on the experimental malingerers and the patients. The first model contained the visual working memory subtests (Spatial Addition and Symbol Span) and the recognition tasks of the following subtests: Logical Memory, Verbal Paired Associates, Designs, Visual Reproduction. The results showed an overall classification rate of 78.4%, and only Spatial Addition explained a significant amount of variation (p < .001). Subsequent logistic regression analysis and receiver operating characteristic (ROC) analysis supported the discriminatory power of the subtest Spatial Addition. A scaled score cutoff of <4 produced 93% specificity and 52% sensitivity for detection of suboptimal performance. CONCLUSION: The WMS-IV-NL Spatial Addition subtest may provide clinically useful information for the detection of suboptimal performance. PMID- 26882179 TI - Transfer of training benefits requires rules we cannot see (or hear). AB - Although humans show a remarkable ability to make rapid and accurate decisions in novel situations, it is surprisingly difficult to observe transferable benefits when training decision-making performance. The current study investigated whether 2 properties of decision-making-amodal processing and encoding of abstract relationships-could be leveraged to produce transferable training gains, compared with the performance of an active-control group. Experiment 1 showed that training responses to visually presented stimuli (letters) did not transfer to benefit performance for the same stimuli presented in the auditory modality. Therefore, training exercises the integration of modality-specific information, not a supramodal category. However, Experiment 2 showed that when stimuli share an abstract rule, training transfers to new materials that conform to the same modality and rule, and to analogous rules in a new modality. Therefore, transfer of training benefits requires an abstract code that can be generalized to new stimulus sets. (PsycINFO Database Record PMID- 26882180 TI - Independent planning of timing and sequencing for complex movements. AB - The current studies examined the processes involved in response sequencing and timing initiation for complex, multiple-component movements. Participants performed a 3 key-press sequence in simple and choice reaction time (RT) paradigms (Experiment 1), or a study time paradigm that allowed the participants to control the foreperiod delay, which is thought to reflect advance preparation duration (Experiment 2). Sequencing complexity was manipulated by using either the same hand and effector for all key presses (low complexity) or different hands/effectors across key presses (high complexity) while timing initiation complexity was manipulated by using either an isochronous (low complexity) or nonisochronous (high complexity) timing pattern. Increasing sequencing complexity had little effect on simple RT but increased participant-controlled foreperiod delay (i.e., study time). Conversely, increasing timing initiation complexity had no effect on foreperiod delay but increased simple RT. These results provide compelling evidence that in a simple RT paradigm, sequencing preparation is performed during the foreperiod while preparation of timing initiation is delayed until the RT interval. Furthermore, choice RT increased with sequencing complexity and was relatively unaffected by timing initiation complexity, indicative of sequencing preparation occurring during the choice RT interval and preparation of timing initiation occurring online. Collectively, the data indicate a dissociation and independence of the preparation of timing initiation and sequencing for complex movements. (PsycINFO Database Record PMID- 26882181 TI - Dance expertise modulates behavioral and psychophysiological responses to affective body movement. AB - The present study shows how motor expertise increases individuals' sensitivity to others' affective body movement. This enhanced sensitivity is evident in the experts' behavior and physiology. Nineteen affective movement experts (professional ballet dancers) and 24 controls watched 96 video clips of emotionally expressive body movements while they performed an affect rating task (subjective response), and their galvanic skin response was recorded (physiological response). The movements in the clips were either sad or happy, and in half of the trials, movements were played in the order in which they are learned (forward presentation), and in the other half, movements were played backward (control condition). Results showed that motor expertise in affective body movement specifically modulated both behavioral and physiological sensitivity to others' affective body movement, and that this sensitivity is particularly strong when movements are shown in the way they are learnt (forward presentation). The evidence is discussed within current theories of proprioceptive arousal feedback and motor simulation accounts. (PsycINFO Database Record PMID- 26882182 TI - Can multiple previous treatment-requiring rejections affect biventricular myocardial function in heart transplant recipients? A two-dimensional speckle tracking study. PMID- 26882183 TI - A real world single centre experience using the STENTYS self-expanding coronary stent. PMID- 26882184 TI - Fontan circulation causes early, severe liver damage. Should we offer patients a tailored strategy? AB - BACKGROUND: In patients with Fontan circulation, the liver is profoundly affected by chronic venous stasis. Little is known about early hepatic changes in this population. METHODS: We performed echocardiography, abdominal ultrasound, liver elastography, cardiac catheterization, esophago-gastro-duodenoscopy and calculated MELD-XI score in 64 Fontan patients (69% minors), at an interval of 1 15years since Fontan. RESULTS: Cardiac output remained stable in the first 5years after Fontan, then significantly decreased (r=-0.45, p(r=0)=0.003). NYHA class significantly increased after Fontan. Patients in NYHA class II/III (n=21, 14 minors) had significantly higher hepatic pressures, but normal ventricular function and pulmonary vascular resistances (PVR). Patients with pulmonary arterial pressure (PAP) >=15mmHg (n=12, 6 minors) and those with PVR>=2WU*m(2) (n=27, 25 minors), had higher hepatic pressures (p<0.0001), a higher incidence of liver collaterals and/or esophageal varices (p<0.0001) and splenomegaly (p<0.02). Liver stiffness (LS) was elevated in most patients (median, 25th-75th percentile:17.3KPa, 14.1-21.4). It rapidly increased during the first 5-years after Fontan, compared to the following 5-years (from 12.2KPa, 9.8-14.1 to 17.5KPa, 14.3-24.5, p=0.007), then remained stable (19.1KPa, 16.9-22.6, p=0.60). MELD-XI score increased linearly with the time interval since Fontan (r=0.31, p(r=0)=0.01). For patients above 12years we found a linear correlation between LS and MELD-XI score in the 6-15years period after Fontan (r=0.40. p(r=0)=0.04). The overall incidence of established liver cirrhosis was 22%. CONCLUSIONS: This is the largest study showing that Fontan circulation prompts early, progressive and eventually irreversible liver damage. Precautions should be taken immediately after Fontan, to protect this fragile population. PMID- 26882185 TI - A girl with 'six needles' in the heart. PMID- 26882186 TI - Antidepressant use, clinical depression and mortality in patients with heart failure. PMID- 26882187 TI - Details about diabetes mellitus in reported patients with Takotsubo syndrome, and its importance in unraveling the pathophysiology of the disease. PMID- 26882188 TI - Aortic regurgitation secondary to an aberrant mitral chord traversing the aortic valve. PMID- 26882189 TI - Comparing inflammatory cell density in the myocardium and coronary arteries in rheumatoid arthritis patients versus controls with myocardial infarction: A post mortem case-control study. PMID- 26882190 TI - Levosimendan meta-analyses: Is there a pattern in the effect on mortality? AB - BACKGROUND: Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non cardiac surgery. This variety of data has been re-analysed in 25 meta-analyses from 15 different international research groups, based on different rationales to select the studies included. METHODS: We here review all previously published meta-analyses on levosimendan to determine any common denominators for its effects on patient mortality. In addition, we also perform a comparative meta analysis of the six phase II and III randomized double-blind trials which were taken into consideration by the regulatory authorities for the purpose of introducing levosimendan into the market. RESULTS: Irrespective of clinical setting or comparator, all meta-analyses consistently show benefits for levosimendan, with lower relative risk (or odds ratio) for patient mortality. In 3/25 of the meta-analyses these beneficial trends did not reach statistical significance, while in 22/25 significance was reached. The relative risk is consistent overall, and very similar to that obtained in our own meta-analysis that considered only the 'regulatory' studies. CONCLUSION: The existing meta analyses, now based on a population of over 6000 patients, provide the general message of significant benefits for levosimendan in terms of patient mortality. The weight of evidence is now clearly in favour of usefulness/efficacy of levosimendan, with data from multiple randomized trials and meta-analyses. PMID- 26882191 TI - Ablation of an electrical storm in a patient with giant cell myocarditis using continuous flow left ventricular assist device and percutaneous right ventricular assist device. PMID- 26882192 TI - Efficacy and safety of bivalirudin versus heparin in patients undergoing percutaneous coronary intervention: A meta-analysis of randomized controlled trials. AB - BACKGROUND: The efficacy and safety of bivalirudin versus heparin in patients undergoing percutaneous coronary intervention (PCI)(1) remains controversial in to date. Our meta-analysis was undertaken to evaluate the efficacy and safety of bivalirudin compared with heparin in patients undergoing PCI. METHODS: We searched PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for randomized controlled trials (RCTs).(2) The primary efficacy endpoint was mortality. Secondary efficacy endpoints were incidence of major adverse cardiovascular events (MACE),(3) myocardial infarction (MI),(4) target vessel revascularization (TVR)(5) and stent thrombosis up to 30days and 1year. The safety endpoint was major bleeding up to 30days. Subgroup analyses were also conducted according to the clinical status of patients and the different use rate of GPI in two groups. RESULTS: 17 RCTs met the including criteria and 40,655 patients were included. No significant difference was observed in mortality (risk ratio [RR](6) 0.90; 95% confidence interval [CI](7) 0.77 to 1.05; p=0.19; I(2)=20%) and the risk of MACE (RR 1.02; 95% CI 0.96 to 1.09; p=0.45; I(2)=37%). Bivalirudin increased the risk of MI (RR 1.10; 95% CI 1.02 to 1.19; p=0.01; I(2)=13%), TVR (RR 1.20; 95% CI 1.04 to 1.38; p=0.01; I(2)=6%) and stent thrombosis (RR 1.32; 95% CI 1.08 to 1.60; p=0.006; I(2)=0%) but decreased the risk of major bleeding (RR 0.54; 95% CI 0.48 to 0.61; p<0.00001; I(2)=0). CONCLUSION: Bivalirudin is associated with higher risk of MI, stent thrombosis and TVR but lower risk of major bleeding compared with heparin. The reduction of major bleeding is associated with the glycoprotein platelet IIb/IIIa inhibitor (GPI)(8) use rate. PMID- 26882193 TI - "Leadless" pacing of the left ventricle in adult congenital heart disease. PMID- 26882194 TI - Massive myocardial aneurysm due to inferior to posterior myocardial infarction complicated with right-sided heart failure in a 36-year-old male. PMID- 26882195 TI - Molecular functionalization of surfaces for device applications. PMID- 26882196 TI - The right prescriptions for reducing diagnostic errors?: Institute of Medicine report issues wakeup call on errors, but questions remain concerning key recommendations. PMID- 26882197 TI - Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens. AB - BACKGROUND: The objective of the current study was to establish a process for validating immunohistochemistry (IHC) protocols for use on the Cellient cell block (CCB) system. METHODS: Thirty antibodies were initially tested on CCBs using IHC protocols previously validated on formalin-fixed, paraffin-embedded tissue (FFPE). Cytology samples were split to generate thrombin cell blocks (TCB) and CCBs. IHC was performed in parallel. Antibody immunoreactivity was scored, and concordance or discordance in immunoreactivity between the TCBs and CCBs for each sample was determined. Criteria for validation of an antibody were defined as concordant staining in expected positive and negative cells, in at least 5 samples each, and concordance in at least 90% of the samples total. Antibodies that failed initial validation were retested after alterations in IHC conditions. RESULTS: Thirteen of the 30 antibodies (43%) did not meet initial validation criteria. Of those, 8 antibodies (calretinin, clusters of differentiation [CD] 3, CD20, CDX2, cytokeratin 20, estrogen receptor, MOC-31, and p16) were optimized for CCBs and subsequently validated. Despite several alterations in conditions, 3 antibodies (Ber-EP4, D2-40, and paired box gene 8 [PAX8]) were not successfully validated. CONCLUSIONS: Nearly one-half of the antibodies tested in the current study failed initial validation using IHC conditions that were established in the study laboratory for FFPE material. Although some antibodies subsequently met validation criteria after optimization of conditions, a few continued to demonstrate inadequate immunoreactivity. These findings emphasize the importance of validating IHC protocols for methanol-fixed tissue before clinical use and suggest that optimization for alcohol fixation may be needed to obtain adequate immunoreactivity on CCBs. PMID- 26882198 TI - Aurophilicity in Action: Fine-Tuning the Gold(I)-Gold(I) Distance in the Excited State To Modulate the Emission in a Series of Dinuclear Homoleptic Gold(I)-NHC Complexes. AB - The solution-state emission profiles of a series of dinuclear Au(I) complexes 4-6 of the general formula Au2(NHC-(CH2)n-NHC)2Br2, where NHC = N-benzylbenzimidazol 2-ylidene and n = 1-3, were found to be markedly different from each other and dependent on the presence of excess bromide. The addition of excess bromide to the solutions of 4 and 6 leads to red shifts of ca. 60 nm, and in the case of 5, which is nonemissive when neat, green luminescence emerges. A detailed computational study undertaken to rationalize the observed behavior revealed the determining role aurophilicity plays in the photophysics of these compounds, and the formation of exciplexes between the complex cations and solvent molecules or counterions was demonstrated to significantly decrease the Au-Au distance in the triplet excited state. A direct dependence of the emission wavelength on the strength of the intracationic aurophilic contact allows for a controlled manipulation of the emission energy by varying the linker length of a diNHC ligand and by judicial choice of counterions or solvent. Such unique stimuli responsive solution-state behavior is of interest to prospective applications in medical diagnostics, bioimaging, and sensing. In the solid, the investigated complexes are intensely phosphorescent and, notably, 5 and 6 exhibit reversible luminescent mechanochromism arising from amorphization accompanied by the loss of co-crystallized methanol molecules. The mechano-responsive properties are also likely to be related to changes in bromide coordination and the ensuing alterations of intramolecular aurophilic interactions. Somewhat surprisingly, the photophysics of NHC ligand precursors 2 and 3 is related to the formation of ground-state associates with bromide counterions through hydrogen bonding, whereas 1 does not appear to bind its counterions. PMID- 26882200 TI - Error in Term Definition. PMID- 26882201 TI - SUICIDAL DEPRESSED PATIENTS RESPOND LESS WELL TO ANTIDEPRESSANTS IN THE SHORT TERM. AB - BACKGROUND: Suicidal thoughts and behaviors could be associated to a poor response to antidepressant treatment, but the exclusion of suicidal patients from randomized clinical trials restricts the available knowledge. In this study, we aimed at defining more precisely the response to antidepressants among suicidal patients and the threshold of suicidality that best predicts a poor response. METHOD: We investigated the short-term response to a new antidepressant treatment of 4,041 depressed outpatients depending on their suicidal status (passive or active suicidal ideation (SI), history of suicide attempts [SAs]), either self rated or clinician-rated. Depression outcomes, measured with the Hospital Anxiety and Depression Scale, and remission rates were compared depending on suicidal status at baseline using logistic regression models. RESULTS: Using either a qualitative or a quantitative approach to measure SI, we found that suicidal patients were less likely to improve or attain remission, but not more likely to worsen, than nonsuicidal patients. In the multivariate analyses, SI (odds ratio [OR] = 1.40; 95% confidence interval [CI]: 1.18-1.65) and a history of SA (OR = 1.39; 95% CI: 1.16-1.66) were the best predictors of nonremission, independently of the class of antidepressant treatment. CONCLUSION: Antidepressant treatment seems to be less effective among those patients that need it most. Clinical trials including suicidal patients are needed to investigate specific treatment options. PMID- 26882199 TI - Structure of a Bacterial Virus DNA-Injection Protein Complex Reveals a Decameric Assembly with a Constricted Molecular Channel. AB - The multi-layered cell envelope structure of Gram-negative bacteria represents significant physical and chemical barriers for short-tailed phages to inject phage DNA into the host cytoplasm. Here we show that a DNA-injection protein of bacteriophage Sf6, gp12, forms a 465-kDa, decameric assembly in vitro. The electron microscopic structure of the gp12 assembly shows a ~150-A, mushroom-like architecture consisting of a crown domain and a tube-like domain, which embraces a 25-A-wide channel that could precisely accommodate dsDNA. The constricted channel suggests that gp12 mediates rapid, uni-directional injection of phage DNA into host cells by providing a molecular conduit for DNA translocation. The assembly exhibits a 10-fold symmetry, which may be a common feature among DNA injection proteins of P22-like phages and may suggest a symmetry mismatch with respect to the 6-fold symmetric phage tail. The gp12 monomer is highly flexible in solution, supporting a mechanism for translocation of the protein through the conduit of the phage tail toward the host cell envelope, where it assembles into a DNA-injection device. PMID- 26882202 TI - Quantum Coherence Facilitates Efficient Charge Separation at a MoS2/MoSe2 van der Waals Junction. AB - Two-dimensional transition metal dichalcogenides (MX2, M = Mo, W; X = S, Se) hold great potential in optoelectronics and photovoltaics. To achieve efficient light to-electricity conversion, electron-hole pairs must dissociate into free charges. Coulomb interaction in MX2 often exceeds the charge transfer driving force, leading one to expect inefficient charge separation at a MX2 heterojunction. Experiments defy the expectation. Using time-domain density functional theory and nonadiabatic (NA) molecular dynamics, we show that quantum coherence and donor acceptor delocalization facilitate rapid charge transfer at a MoS2/MoSe2 interface. The delocalization is larger for electron than hole, resulting in longer coherence and faster transfer. Stronger NA coupling and higher acceptor state density accelerate electron transfer further. Both electron and hole transfers are subpicosecond, which is in agreement with experiments. The transfers are promoted primarily by the out-of-plane Mo-X modes of the acceptors. Lighter S atoms, compared to Se, create larger NA coupling for electrons than holes. The relatively slow relaxation of the "hot" hole suggests long-distance bandlike transport, observed in organic photovoltaics. The electron-hole recombination is notably longer across the MoS2/MoSe2 interface than in isolated MoS2 and MoSe2, favoring long-lived charge separation. The atomistic, time-domain studies provide valuable insights into excitation dynamics in two-dimensional transition metal dichalcogenides. PMID- 26882203 TI - Melatonin prevents cisplatin-induced primordial follicle loss via suppression of PTEN/AKT/FOXO3a pathway activation in the mouse ovary. AB - Premature ovarian failure (POF) is a major side effect of chemotherapy in young cancer patients. To develop pharmaceutical agents for preserving fertility, it is necessary to understand the mechanisms responsible for chemotherapy-induced follicle loss. Here, we show that treatment with cisplatin, a widely used anticancer drug, depleted the dormant follicle pool in mouse ovaries by excessive activation of the primordial follicles, without inducing follicular apoptosis. Moreover, we show that co-treatment with the antioxidant melatonin prevented cisplatin-induced disruption of the follicle reserve. We quantified the various stages of growing follicles, including primordial, primary, secondary, and antral, to demonstrate that cisplatin treatment alone significantly decreased, whereas melatonin co-treatment preserved, the number of primordial follicles in the ovary. Importantly, analysis of the PTEN/AKT/FOXO3a pathway demonstrated that melatonin significantly decreased the cisplatin-mediated inhibitory phosphorylation of PTEN, a key negative regulator of dormant follicle activation. Moreover, melatonin prevented the cisplatin-induced activating phosphorylation of AKT, GSK3beta, and FOXO3a, all of which trigger follicle activation. Additionally, we show that melatonin inhibited the cisplatin-induced inhibitory phosphorylation and nuclear export of FOXO3a, which is required in the nucleus to maintain dormancy of the primordial follicles. These findings demonstrate that melatonin attenuates cisplatin-induced follicle loss by preventing the phosphorylation of PTEN/AKT/FOXO3a pathway members; thus, melatonin is a potential therapeutic agent for ovarian protection and fertility preservation during chemotherapy in female cancer patients. PMID- 26882204 TI - Sexual function and help seeking for urinary incontinence in postmenopausal women. AB - Urinary incontinence (UI) is a common condition, especially in middle-aged and older women. UI is known to affect sexual function. Many women with UI do not consult a doctor about their condition. The aim of this study was to determine the relationship of sexual function and help seeking in postmenopausal women with urinary incontinence. This cross-sectional correlation study took place from March to May 2012. The subjects were selected by a clustered sampling method from various zones of Rasht (North of Iran). The data were collected using personal data forms, Questionnaire for Urinary Incontinence Diagnosis, Incontinence Severity Index, and Incontinence Quality of Life questionnaire. Data were analyzed by SPSS17 at the significant level of P < .05 and then were compared by parametric and nonparametric tests. A total of 313 menopausal women aged 45 to 60 years (mean 52.9) were recruited for the study. The mean sexual function score was 31.07 +/- 7.52. Only 27.3% of subjects seek care for urinary incontinence. There was a significant correlation between sexual function and help seeking. The results of this study indicate that there is a significant correlation between sexual function and help seeking in postmenopausal women who participated in the present study. Health-care professionals should pay more attention to sexual symptoms of UI and make patients aware of available treatments. PMID- 26882205 TI - Perceived exercise barriers and their associations with regular exercise across three age groups of rural women in Taiwan. AB - The purposes of the study were to explore the differences in perceived exercise barriers across three age groups of Taiwanese rural women (30-50, 51-70, and >70 years old) and to examine the associations between perceived exercise barriers and regular exercise behavior. A total of 227 women completed the Self-Reported Exercise Behavior and the Perceived Exercise Barrier Scale. Women older than 70 reported higher physical and psychological barriers and lower administrative barriers than did the younger group. Women who did not exercise regularly tended to have a higher perception of exercise barriers. PMID- 26882206 TI - The Proposal for Smoke-Free Public Housing: Benefits, Challenges, and Opportunities for 2 Million Residents. PMID- 26882207 TI - Adverse Trends in Ischemic Heart Disease Mortality among Young New Yorkers, Particularly Young Black Women. AB - BACKGROUND: Ischemic heart disease (IHD) mortality has been on the decline in the United States for decades. However, declines in IHD mortality have been slower in certain groups, including young women and black individuals. HYPOTHESIS: Trends in IHD vary by age, sex, and race in New York City (NYC). Young female minorities are a vulnerable group that may warrant renewed efforts to reduce IHD. METHODS: IHD mortality trends were assessed in NYC 1980-2008. NYC Vital Statistics data were obtained for analysis. Age-specific IHD mortality rates and confidence bounds were estimated. Trends in IHD mortality were compared by age and race/ethnicity using linear regression of log-transformed mortality rates. Rates and trends in IHD mortality rates were compared between subgroups defined by age, sex and race/ethnicity. RESULTS: The decline in IHD mortality rates slowed in 1999 among individuals aged 35-54 years but not >=55. IHD mortality rates were higher among young men than women age 35-54, but annual declines in IHD mortality were slower for women. Black women age 35-54 had higher IHD mortality rates and slower declines in IHD mortality than women of other race/ethnicity groups. IHD mortality trends were similar in black and white men age 35-54. CONCLUSIONS: The decline in IHD mortality rates has slowed in recent years among younger, but not older, individuals in NYC. There was an association between sex and race/ethnicity on IHD mortality rates and trends. Young black women may benefit from targeted medical and public health interventions to reduce IHD mortality. PMID- 26882208 TI - Discovery of Potent Soluble Epoxide Hydrolase (sEH) Inhibitors by Pharmacophore Based Virtual Screening. AB - There is an increasing interest in the development of soluble epoxide hydrolase (sEH) inhibitors, which block the degradation of endogenous anti-inflammatory epoxyeicosatrienoic acids. Within this study, a set of pharmacophore models for sEH inhibitors was developed. The Specs database was virtually screened and a cell-free sEH activity assay was used for the biological investigation of virtual hits. In total, out of 48 tested compounds, 19 were sEH inhibitors with IC50 < 10 MUM, representing a prospective true positive hit rate of 40%. Six of these compounds displayed IC50 values in the low nanomolar range. The most potent compound 21, a urea derivative, inhibited sEH with an IC50 = 4.2 nM. The applied approach also enabled the identification of diverse chemical scaffolds, e.g. the pyrimidinone derivative 29 (IC50 = 277 nM). The generated pharmacophore model set therefore represents a valuable tool for the selection of compounds for biological testing. PMID- 26882209 TI - Ocular manifestations of X-linked dominant FAM58A mutation in toe syndactyly, telecanthus, anogenital, and renal malformations ('STAR') syndrome. AB - PURPOSE: To report the newest ophthalmic manifestations of a mother-daughter pair diagnosed with toe syndactyly, telecanthus, anogenital and renal malformations (STAR) syndrome, a rare X-linked developmental disorder. METHODS: The medical and ophthalmic records were reviewed for a mother-daughter pair diagnosed with FAM58A confirmed STAR syndrome on chromosome Xq28. RESULTS: The mother at birth had left foot syndactyly, telecanthus, anal stenosis, and clitoromegaly and was told at 19 she had a hypoplastic left kidney. The daughter, born at 38 weeks after a complication of oligohydramnios, had a more severe presentation, demonstrating toe syndactyly, telecanthus, anal stenosis, clitoromegaly, bilateral renal hypoplasia, ureteral reflux, urogenital sinus, and congenital heart disease amongst others. The pair shared similar ophthalmic findings, though those of the daughter were more pronounced. They included bilateral, medial upper eyelid prominences with madarosis, mild peripapillary atrophy, and soft macular drusen with the daughter also displaying optic nerve hypoplasia and peripheral anterior synechia in the iridocorneal angle. CONCLUSION: These ophthalmic findings are the first reported to our knowledge in association with STAR syndrome. The literature frequently demonstrates that patients with developmental anomalies often have ocular manifestations, warranting a full ophthalmic examination when the diagnosis of STAR syndrome has been made or is being considered. PMID- 26882210 TI - Theoretical Characterization of the H-Bonding and Stacking Potential of Two Nonstandard Nucleobases Expanding the Genetic Alphabet. AB - We report a quantum chemical characterization of the non-natural (synthetic) H bonded base pair formed by 6-amino-5-nitro-2(1H)-pyridone (Z) and 2 aminoimidazo[1,2-a]-1,3,5-triazin-4(8H)-one (P). The Z:P base pair, orthogonal to the classical G:C base pair, has been introduced into DNA molecules to expand the genetic code. Our results indicate that the Z:P base pair closely mimics the G:C base pair in terms of both structure and stability. To clarify the role of the NO2 group on the C5 position of the Z base, we compared the stability of the Z:P base pair with that of base pairs having different functional groups at the C5 position of Z. Our results indicate that the electron-donating/-withdrawing properties of the group on C5 have a clear impact on the stability of the Z:P base pair, with the strong electron-withdrawing nitro group achieving the largest stabilizing effect on the H-bonding interaction and the strong electron-donating NH2 group destabilizing the Z:P pair by almost 4 kcal/mol. Finally, our gas-phase and in-water calculations confirm that the Z-nitro group reinforces the stacking interaction with its adjacent purine or pyrimidine ring. PMID- 26882211 TI - Stem cell transplantation for the treatment of immunodeficiency in children: current status and hopes for the future. AB - Primary immunodeficiencies (PID) are rare inherited disorders affecting immune function and can be life-threatening if not treated. Haematopoietic stem cell transplantation (HSCT) offers a curative approach for many of these disorders and gene therapy is increasingly used as an alternative therapeutic strategy for patients lacking a suitable donor. Early diagnosis, improved supportive care and advances in gene and cell therapies have resulted in increased survival rates and improved quality of life. This review describes current strategies employed to improve outcomes in PID, focusing on new developments in HSCT, gene and cell therapy. We also address the challenges associated with newborn screening (NBS) programmes and novel mutations identified through improved diagnostic technology. PMID- 26882212 TI - Feasibility of boar taint classification using a portable Raman device. AB - The feasibility of Raman spectroscopy for boar taint detection and classification was investigated using tainted and untainted backfat samples of 46 boars. For this exploratory study, backfat samples were selected according to their levels of androstenone and skatole as determined by gas chromatography and their sensory score by a trained panel. Raman spectra were collected with a portable device at freshly cut surfaces of frozen-thawed samples. Both inner and outer layers of subcutaneous fat were studied. Their varying level of unsaturation was reflected in the Raman spectra. Partial least squares regression discriminant analysis (PLS DA) was applied to the spectra together with various pre-processing methods. A model using only spectra obtained at the inner layer resulted in the highest classification accuracy for boar taint (81% of samples correctly classified). The discrimination is shown to reflect differences in the degree of fatty acid saturation between tainted and untainted boars. In conclusion, the findings suggest that with further development Raman spectroscopy may be used to classify boar taint. PMID- 26882213 TI - Effect of the use of entire male fat in the production of reduced salt fermented sausages. AB - The effect of the use of entire male fat and salt reduction in dry fermented sausages was evaluated. Four different sausage formulations were manufactured with back fat from gilt or entire male and two different salt contents. The physicochemical parameters, sensory characteristics, texture, lipid composition, volatile compounds and boar taint compounds were analysed. The use of entire male fat produced the highest weight losses producing high hardness and chewiness while salt reduction produced a decrease in hardness. Entire male sausages had the lowest oxidation values due to the low content of C18:2n6 while salt reduction did not affect the oxidation process. Boar taint odour was due to the presence of androstenone and skatole but entire male fat sausages had different generations of volatile compounds. The presence of androstenone was perceived by consumers as abnormal odours but also other sausage characteristics such as texture (high hardness) and oxidation were detected due to the different chemical compositions of entire males versus gilts. PMID- 26882214 TI - Antifouling Polymer Brushes Displaying Antithrombogenic Surface Properties. AB - The contact of blood with artificial materials generally leads to immediate protein adsorption (fouling), which mediates subsequent biological processes such as platelet adhesion and activation leading to thrombosis. Recent progress in the preparation of surfaces able to prevent protein fouling offers a potential avenue to mitigate this undesirable effect. In the present contribution, we have prepared several types of state-of-the-art antifouling polymer brushes on polycarbonate plastic substrate, and investigated their ability to prevent platelet adhesion and thrombus formation under dynamic flow conditions using human blood. Moreover, we compared the ability of such brushes--grafted on quartz via an adlayer analogous to that used on polycarbonate--to prevent protein adsorption from human blood plasma, assessed for the first time by means of an ultrahigh frequency acoustic wave sensor. Results show that the prevention of such a phenomenon constitutes one promising route toward enhanced resistance to thrombus formation, and suggest that antifouling polymer brushes could be of service in biomedical applications requiring extensive blood-material surface contact. PMID- 26882215 TI - Tunable Radiation Response in Hybrid Organic-Inorganic Gate Dielectrics for Low Voltage Graphene Electronics. AB - Solution-processed semiconductor and dielectric materials are attractive for future lightweight, low-voltage, flexible electronics, but their response to ionizing radiation environments is not well understood. Here, we investigate the radiation response of graphene field-effect transistors employing multilayer, solution-processed zirconia self-assembled nanodielectrics (Zr-SANDs) with ZrOx as a control. Total ionizing dose (TID) testing is carried out in situ using a vacuum ultraviolet source to a total radiant exposure (RE) of 23.1 MUJ/cm(2). The data reveal competing charge density accumulation within and between the individual dielectric layers. Additional measurements of a modified Zr-SAND show that varying individual layer thicknesses within the gate dielectric tuned the TID response. This study thus establishes that the radiation response of graphene electronics can be tailored to achieve a desired radiation sensitivity by incorporating hybrid organic-inorganic gate dielectrics. PMID- 26882216 TI - Incidence rates of suicidal behaviors and treated depression in patients with and without psoriatic arthritis using the Clinical Practice Research Datalink. AB - OBJECTIVE: To estimate rates of suicidal behaviors and treated depression in patients with psoriatic arthritis (PsA) in comparison to non-PsA patients. METHODS: Using the Clinical Practice Research Datalink, we conducted a cohort study of patients with PsA compared to non-PsA patients. Patients with codes for suicidal behaviors (ideation, attempts, and suicide) and treated depression (diagnosis plus anti-depressant prescription) recorded during follow-up were identified as cases. We estimated incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for each outcome and stratified results in the PsA cohort by receipt of systemic PsA drugs. RESULTS: The rates of suicide ideation, attempt, and suicide were similar for PsA and non-PsA patients [IRR = 0.99 (95%CI: 0.67-1.47), IRR = 1.07 (95%CI: 0.86-1.34), and 0.34 (95%CI: 0.05-2.48), respectively] and rates of suicidal behaviors were slightly higher among PsA patients who received PsA drugs compared to those who did not. PsA patients had slightly higher rate of treated depression compared to non-PsA patients [IRR = 1.38 (95%CI: 1.27-1.49)] and were significantly higher in PsA patients who received drugs [IRR = 1.59 (95%CI: 1.35-1.86)]. CONCLUSIONS: Rate of depression was higher in patients with PsA compared to non-PsA patients. The rate of suicidal behaviors was similar between the two cohorts. PMID- 26882217 TI - A note on the magnitude of hazard ratios. PMID- 26882218 TI - Novel drug discovery approaches for treating arenavirus infections. AB - INTRODUCTION: Arenaviruses are enveloped negative stranded viruses endemic in Africa, Europe and the Americas. Several arenaviruses cause severe viral hemorrhagic fever with high mortality in humans and pose serious public health threats. So far, there are no FDA-approved vaccines and therapeutic options are restricted to the off-label use of ribavirin. The major human pathogenic arenaviruses are classified as Category A agents and require biosafety level (BSL)-4 containment. AREAS COVERED: Herein, the authors cover the recent progress in the development of BSL2 surrogate systems that recapitulate the entire or specific steps of the arenavirus life cycle and are serving as powerful platforms for drug discovery. Furthermore, they highlight the identification of selected novel drugs that target individual steps of arenavirus multiplication describing their discovery, their targets, and mode of action. EXPERT OPINION: The lack of effective drugs against arenaviruses is an unmatched challenge in current medical virology. Novel technologies have provided important insights into the basic biology of arenaviruses and the mechanisms underlying virus-host cell interaction. Significant progress of our understanding of how the virus invades the host cell paved the way to develop powerful novel screening platforms. Recent efforts have provided a range of promising drug candidates currently under evaluation for therapeutic intervention in vivo. PMID- 26882219 TI - Exposure to electromagnetic field attenuates oxygen-glucose deprivation-induced microglial cell death by reducing intracellular Ca(2+) and ROS. AB - Purpose The aim of this research was to demonstrate the protective effects of electromagnetic field (EMF) exposure on the human microglial cell line, HMO6, against ischemic cell death induced by in vitro oxygen-glucose deprivation (OGD). Materials and methods HMO6 cells were cultured for 4 h under OGD with or without exposure to EMF with different combinations of frequencies and intensities (10, 50, or 100 Hz/1 mT and 50 Hz/0.01, 0.1, or 1 mT). Cell survival, intracellular calcium and reactive oxygen species (ROS) levels were measured. Results OGD caused significant HMO6 cell death as well as elevation of intracellular Ca(2+) and ROS levels. Among different combinations of EMF frequencies and intensities, 50 Hz/1 mT EMF was the most potent to attenuate OGD-induced cell death and intracellular Ca(2+) and ROS levels. A significant but less potent protective effect was also found at 10 Hz/1 mT, whereas no protective effect was found at other combinations of EMF. A xanthine oxidase inhibitor reversed OGD-induced ROS production and cell death, while NADPH oxidase and mitochondrial respiration chain complex II inhibitors did not affect cell death. Conclusions 50 Hz/1 mT EMF protects human microglial cells from OGD-induced cell death by interfering with OGD-induced elevation of intracellular Ca(2+) and ROS levels, and xanthine oxidase is one of the main mediators involved in OGD-induced HMO6 cell death. Non invasive treatment of EMF radiation may be clinically useful to attenuate hypoxic ischemic brain injury. PMID- 26882220 TI - A recurrent TP63 mutation causing EEC3 and Rapp-Hodgkin syndromes. AB - The ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3; OMIM #604292), the Rapp-Hodgkin syndrome (RHS), and various other syndromes are caused by mutations in the TP63 gene, which encodes a p53-like transcription factor. Here, we report on a woman aged 37 years and her daughter aged 3 years with the previously reported c.1028G>A (p.Arg343Gln) mutation in exon 8 of TP63. The mother lacked ectrodactyly, indicating a diagnosis of RHS, whereas the girl presented with all three major features (ectrodactyly, ectodermal dysplasia, clefting) and different minor features (including small and brittle nails, and recurrent conjunctivitis believed to be because of stenotic and blocked nasolacrimal ducts) of the EEC3 syndrome. The EEC and EEC-like syndromes are usually distinguished on the basis of the clinical findings; however, these syndromes show a huge variability in features because of variable expressivity and incomplete penetrance, making the correct clinical assignment difficult. In EEC3 syndrome and RHS, a clustering of mutations in the different domains of TP63 can be observed. Our findings indicate the clinical variability with TP63 mutations and underline that in the case of two syndromes being clinically possible in a patient, the final diagnosis should be assigned only after molecular diagnostics. PMID- 26882221 TI - Relaxation Editing Using Long-Lived States and Coherences for Analysis of Mixtures. AB - Nuclear magnetic resonance (NMR) is a powerful tool for structural and dynamical studies of molecules. Although widely applicable, the search for novel spectral editing methods that facilitate spectral assignment of peaks in high-resolution NMR is highly desirable. Earlier, the sensitivity of lifetime of spin states (spin-lattice relaxation time, T1) and coherences (spin-spin relaxation time, T2) to the immediate environment was utilized for spectral editing in solution NMR. Long-lived states (LLS) and coherences (LLCs) were recently uncovered to have longer and more domain sensitive lifetime than other type of states and coherences. Herein, this longevity and increased sensitivity of LLS and LLC lifetime is utilized for more enhanced dispersion in relaxation editing in NMR. The generality of the method as a powerful tool in spectral editing is confirmed with molecules containing a mixture of strongly and weakly coupled spin systems and finally with metabolomic mixture. Extension to insensitive nuclei enhanced by polarization transfer (INEPT), correlation spectroscopy (COSY), and heteronuclear single quantum coherence (HSQC) are also demonstrated. PMID- 26882222 TI - Evaluation of a Novel Mobile Exergame in a School-Based Environment. AB - Physical inactivity is increasing among children globally and has been directly linked to the growing problems of overweight and obesity. We aim to assess the impact of a new mobile exergame, MobileKids Monster Manor (MKMM), in a school based setting. MKMM, developed with input from youth to enhance physical activity, is wirelessly connected to an accelerometer-based activity monitor. Forty-two healthy students (11.3 +/- 1.2 years old and 0.28 +/- 1.29 body-mass index [BMI] z-score) participated in a randomized 4-week crossover study to evaluate the game intervention. The two study arms consisted of week-long baseline, game intervention/control, washout, and control/game intervention phases. All participants were required to wear an activity monitor at all times to record steps and active minutes for the study duration. MKMM was used during each arm's respective intervention week, during which children were asked to play the game at their convenience. When children were exposed to the game, an increase compared with the control phase of 2,934 steps per day (p = 0.0004, 95% CI 1,434-4,434) and 46 active minutes per day (p = 0.001, 95% CI 20-72) from baseline (12,299 steps/day and 190 active minutes/day) was observed. A linear regression model showed that MKMM yielded a greater increase in steps and active minutes per day among children with a higher BMI z-score, showing 10 percent more steps per day and 14 percent more active minutes per day relative to baseline, per unit increase in BMI z-score. In conclusion, MKMM increased steps and active minutes in a school-based environment. This suggests that mobile exergames could be useful tools for schools to promote physical activity and combat obesity in adolescents. PMID- 26882223 TI - Intensive Glycemic Control in Type 2 Diabetes Mellitus -- A Balancing Act of Latent Benefit and Avoidable Harm: A Teachable Moment. PMID- 26882224 TI - SULF2 Expression Is a Potential Diagnostic and Prognostic Marker in Lung Cancer. AB - AIMS: Lung cancer is one of the most deadly cancers; median survival from diagnosis is less than one year in those with advanced disease. Novel lung cancer biomarkers are desperately needed. In this study, we evaluated SULF2 expression by immunohistochemistry and its association with overall survival in a cohort of patients with non-small cell lung cancer (NSCLC). We also looked for the presence of SULF2 protein in plasma to evaluate its potential as an early detection biomarker for NSCLC. METHODS: We identified patients who underwent surgical resection for pulmonary adenocarcinoma or squamous cell carcinoma at our institution. A section from each paraffin-embedded specimen was stained with a SULF2 antibody. A pathologist determined the percentage and intensity of tumor cell staining. Survival analysis was performed using a multivariate Cox proportional hazards model. Using a novel SULF2 ELISA assay, we analyzed plasma levels of SULF2 in a small cohort of healthy donors and patients with early stage NSCLC. RESULTS: SULF2 staining was present in 82% of the lung cancer samples. Squamous cell carcinomas had a higher mean percentage of staining than adenocarcinomas (100% vs. 60%; p<0.0005). After adjusting for age, sex, race, histologic type, stage, and neoadjuvant therapy, there was a non-significant (31%; p = 0.65) increase in the risk of death for patients with adenocarcinoma with SULF2 staining in tumor cells. In contrast, there was a significant decrease in the risk of death (89%; p = 0.02) for patients with squamous cell carcinoma with SULF2 staining in tumor cells. SULF2 protein was present in plasma of patients with early stage NSCLC, and soluble SULF2 levels increased with age. Finally, plasma SULF2 levels were significantly elevated in early stage NSCLC patients, compared to healthy controls. CONCLUSIONS: Tumor expression of SULF2 may affect prognosis in NSCLC, while blood SULF2 levels may have a significant role in the diagnosis of this fatal disease. PMID- 26882225 TI - Tailored Enrichment Strategies and Stereotypic Behavior in Captive Individually Housed Macaques (Macaca spp.). AB - The welfare of nonhuman animals in captivity is widely dependent on the natural psychological, physical, and behavioral needs of the animals and how adequately these needs are met. Inability to engage in natural behaviors can lead to chronic stress and expression of stereotypic behavior. The majority of research on decreasing stereotypic behavior in captivity addresses problems at the group level and does not account for individual variability in each animal's needs, history, and preferences. This study combined physiological and behavioral measures of well being to comprehensively assess the unique needs of individually housed captive macaques (Macaca spp.) with the aim of developing tailored welfare strategies. Behavioral and hormonal data were collected under 2 conditions: baseline and individualized enrichment. The results showed a significant decrease in stereotypic behavior under the enrichment condition. Additionally, 7 out of 9 individuals showed a decrease in fecal glucocorticoid (stress hormone) levels, indicating a reduction in hypothalamic-pituitary-adrenal activity. Addressing welfare on an individual, rather than group, level allows for a better overall characterization of well being and maximizes the probability of improving the welfare of each animal. PMID- 26882226 TI - Fluid Management in Acute Kidney Injury. AB - The goal of fluid therapy in critical care medicine is to restore hemodynamic stability and vital organ perfusion while avoiding interstitial edema. Acute kidney injury (AKI) is a common complication in critically ill patients. Decisions regarding fluid management in critically ill patients with AKI are difficult, as these patients often have accompanying oliguria as well as body fluid overload. Both hypovolemia and volume overload are associated with increased morbidity and mortality in critical care patients; therefore, accurate assessment of the intravascular volume status as well as the response to fluid replacement remains one of the most challenging and important issues for clinicians in daily practice. Newer dynamic preload indexes, such as stroke volume variation and pulse pressure variation in conjunction with the end expiratory occlusion test and the passive leg-raising test, have been shown to be more reliable indicators for accurate evaluation of fluid responsiveness in critically ill patients than static pressure measurements, such as central vein pressure and pulmonary artery occlusion pressure. In patients with established AKI who are unresponsive to fluid administration, fluid restriction is the treatment of choice. When fluid therapy is indicated for AKI patients, isotonic crystalloids should be the preferred agents in the absence of hemorrhagic shock. Balanced solutions may reduce the risk of hyperchloremic acidosis and kidney injury. In summary, volume management is an integral part of the care of critically ill patients with AKI. An optimal strategy might involve a timely period of guided fluid resuscitation with appropriate solutions, followed by an appropriate fluid balance. PMID- 26882227 TI - MENGA: A New Comprehensive Tool for the Integration of Neuroimaging Data and the Allen Human Brain Transcriptome Atlas. AB - INTRODUCTION: Brain-wide mRNA mappings offer a great potential for neuroscience research as they can provide information about system proteomics. In a previous work we have correlated mRNA maps with the binding patterns of radioligands targeting specific molecular systems and imaged with positron emission tomography (PET) in unrelated control groups. This approach is potentially applicable to any imaging modality as long as an efficient procedure of imaging-genomic matching is provided. In the original work we considered mRNA brain maps of the whole human genome derived from the Allen human brain database (ABA) and we performed the analysis with a specific region-based segmentation with a resolution that was limited by the PET data parcellation. There we identified the need for a platform for imaging-genomic integration that should be usable with any imaging modalities and fully exploit the high resolution mapping of ABA dataset. AIM: In this work we present MENGA (Multimodal Environment for Neuroimaging and Genomic Analysis), a software platform that allows the investigation of the correlation patterns between neuroimaging data of any sort (both functional and structural) with mRNA gene expression profiles derived from the ABA database at high resolution. RESULTS: We applied MENGA to six different imaging datasets from three modalities (PET, single photon emission tomography and magnetic resonance imaging) targeting the dopamine and serotonin receptor systems and the myelin molecular structure. We further investigated imaging-genomic correlations in the case of mismatch between selected proteins and imaging targets. PMID- 26882228 TI - Attentional and Contextual Priors in Sound Perception. AB - Behavioral and neural studies of selective attention have consistently demonstrated that explicit attentional cues to particular perceptual features profoundly alter perception and performance. The statistics of the sensory environment can also provide cues about what perceptual features to expect, but the extent to which these more implicit contextual cues impact perception and performance, as well as their relationship to explicit attentional cues, is not well understood. In this study, the explicit cues, or attentional prior probabilities, and the implicit cues, or contextual prior probabilities, associated with different acoustic frequencies in a detection task were simultaneously manipulated. Both attentional and contextual priors had similarly large but independent impacts on sound detectability, with evidence that listeners tracked and used contextual priors for a variety of sound classes (pure tones, harmonic complexes, and vowels). Further analyses showed that listeners updated their contextual priors rapidly and optimally, given the changing acoustic frequency statistics inherent in the paradigm. A Bayesian Observer model accounted for both attentional and contextual adaptations found with listeners. These results bolster the interpretation of perception as Bayesian inference, and suggest that some effects attributed to selective attention may be a special case of contextual prior integration along a feature axis. PMID- 26882229 TI - A Finger-Stick Whole-Blood HIV Self-Test as an HIV Screening Tool Adapted to the General Public. AB - BACKGROUND: In 2013, the French Health Authority approved the use of HIV self tests in pharmacies for the general public. This screening tool will allow an increase in the number of screenings and a reduction in the delay between infection and diagnosis, thus reducing the risk of further infections. We previously compared 5 HIV-self test candidates (4 oral fluid and one whole blood) and demonstrated that the whole blood HIV test exhibited the optimal level of performance (sensitivity/specificity). We studied the practicability of an easy to-use finger-stick whole blood HIV self-test "autotest VIH(r)", when used in the general public. METHODS AND MATERIALS: This multicenter cross-sectional study involved 411 participants from the Parisian region (AIDES and HF association) between April and July 2014 and was divided into 2 separate studies: one evaluating the capability of participants to obtain an interpretable result using only the information notice, and a second evaluating the interpretation of test results, using a provided chart. RESULTS: A total of 411 consenting participants, 264 in the first study and 147 in the second, were included. All participants were over 18 years of age. In the first study, 99.2% of the 264 participants correctly administered the auto-test, and 21.2% needed, upon their request, telephone assistance. Ninety-two percent of participants responded that the test was easy/very easy to perform, and 93.5% did not find any difficulty obtaining a sufficient good quantity of blood. In the second study, 98.1% of the 147 participants correctly interpreted the results. The reading/interpretation errors concerned the negative (2.1%) or the indeterminate (3.3%) auto-tests. CONCLUSIONS: The success rate of handling and interpretation of this self-test is very satisfactory, demonstrating its potential for use by the general public and its utility to increase the number of opportunities to detect HIV patients. PMID- 26882230 TI - Metabolic Syndrome in South African Patients with Severe Mental Illness: Prevalence and Associated Risk Factors. AB - BACKGROUND: There is a surge of cardiovascular disease (CVD) in Africa. CVD is the leading cause of mortality among patients with severe mental illness (SMI) in developed countries, with little evidence from the African context. OBJECTIVE: To determine the prevalence and risk factors for MetS among South African patients with SMI. METHOD: In a cross sectional study, individuals with SMI treated with antipsychotics and a control group without a mental illness, matched for age, gender and ethnicity were evaluated for MetS using the 2009 Joint Interim statement (JIS) criteria. RESULTS: Of the 276 study group subjects, 65.9% were male, 84.1% black African, 9.1% white, 5.4% of Indian descent and 1.5% coloured (mixed race) with a mean age of 34.7 years (+/-12.5). Schizophrenia was the most common diagnosis (73.2%) and 40% were taking first generation antipsychotics. The prevalence of MetS was 23.2% (M: 15.4%, F: 38.3%) in the study group and 19.9% (M: 11.9%, F: 36.3%) in the control group (p = 0.4). MetS prevalence was significantly higher in study subjects over 55 years compared to controls (p = 0.03). Increased waist circumference (p< 0.001) and low high density lipoprotein (HDL) cholesterol (p = 0.003) were significantly more prevalent in study subjects compared to controls. In study subjects, risk factors associated with MetS included age (OR: 1.09, 95% CI 1.06-1.12, p < 0.001), female gender (OR: 2.19, 95% CI 1.06-4.55, p = 0.035) and Indian descent (OR: 5.84, 95% CI 1.66-20.52, p = 0.006) but not class of antipsychotic (p = 0.26). CONCLUSION: The overall MetS prevalence was not increased in patients with SMI compared to controls; however, the higher prevalence of the individual components (HDL cholesterol and waist circumference) suggests an increased risk for CVD, especially in patients over 55 years. PMID- 26882231 TI - Retrospective Cohort Study of Gender Differential in Risk of Multiple Sclerosis in Kuwait. AB - BACKGROUND: Despite an increase in the incidence of multiple sclerosis (MS) in the Middle-East, there is a paucity of published data on sex ratio among MS patients in the region. Therefore, this retrospective cohort study determined sex ratio by year of birth of MS patients born from January 1, 1950, to December 31, 2000, who were diagnosed and registered in the Kuwait National MS Registry till April 30, 2013. METHODS: Patients were classified into 5-year periods according to their year of birth. Sex ratio (female:male) and its 95% CI for each period were computed. Using binomial logistic regression, sex ratio in MS patients was modeled with respect to year of birth and nationality. RESULTS: Of 1,035 patients with MS, 675 (65.2%) were women and 798 (77.1%) Kuwaiti. Sex ratio (female:male) of MS cases for entire study period was 1.9 (range 0.4-3.0). Multivariable logistic regression model showed that with each passing year of birth, there was statistically significant 8% increase in sex ratio (female:male) for vulnerability to MS risk (adjusted OR 1.08; 95% CI 1.06-1.09; p < 0.001). CONCLUSIONS: There was a statistically significant steady increase on logarithmic scale in the gender disparity for MS risk over the study period. This study from the Middle-East adds to the existing persuasive evidence of enhanced MS risk in women. Further insight in the context of differential risk factors including the role of sex hormones and vitamin D deficiency in MS pathogenesis may help designing preventive strategies. PMID- 26882232 TI - Dual pH-responsive 5-aminolevulinic acid pseudopolyrotaxane prodrug micelles for enhanced photodynamic therapy. AB - Novel 5-aminolevulinic acid (ALA) pseudopolyrotaxane prodrug micelles with dual pH-responsive properties were prepared by the host-guest interaction of alpha cyclodextrin (alpha-CD) and poly(ethylene glycol) (PEG). The micelles exhibited pH dependent cellular uptake and pH-sensitive ALA release, enabling enhanced photodynamic therapy. PMID- 26882233 TI - The Idiopathic Intracranial Hypertension Treatment Trial: A Long-Time Coming but Worth the Wait. PMID- 26882234 TI - How Neurologists and Neuro-Ophthalmologists Think. PMID- 26882235 TI - Innocent Until Proven Guilty. PMID- 26882237 TI - What Do We Really Know About Translaminar Pressure? PMID- 26882238 TI - What Do We Really Know About Translaminar Pressure?: Response. PMID- 26882239 TI - Preparation and Characterization of Biochars from Eichornia crassipes for Cadmium Removal in Aqueous Solutions. AB - The study investigated the preparation and characterization of biochars from water hyacinth at 300 degrees C to 700 degrees C for cadmium (Cd) removal from aqueous solutions. The adsorption process was dominated by oxygen-containing functional groups with irregular surfaces via esterification reactions. Furthermore, the mineral components in the biochars also contributed to Cd absorption through precipitation. Parameters such as the effects of solution pH, contact time, and initial concentration were studied. The optimum pH value was observed at 5.0, in which nearly 90% of Cd was removed. The maximum Cd adsorption capacities based on the Langmuir isotherm were calculated at 49.837, 36.899, and 25.826 mg g(-1). The adsorption processes of the biochars followed the pseudo second-order kinetics, with the equilibrium achieved around 5 h. The biochar from E. crassipes is a promising adsorbent for the treatment of wastewater, which can in turn convert one environmental problem to a new cleaning Technology. PMID- 26882240 TI - Hypoxia-inducible factor (HIF) inhibitors: a patent survey (2011-2015). AB - INTRODUCTION: Hypoxia-inducible factor (HIF)-1alpha regulates the expression of genes involved in angiogenesis, cellular energy metabolism, and cell survival during cancer development. The increased expression of HIF-1alpha in most solid tumors is associated with poor prognoses and therapeutic outcomes. Therefore, HIF has been recognized as an attractive target for cancer therapy, and many HIF inhibitors have been reported. AREAS COVERED: This patent survey summarizes the information about patented HIF inhibitors over the last 5 years (2011-2015). EXPERT OPINION: Although many of the HIF inhibitors reviewed in this patent survey possess inhibitory activity against cancer and HIF-related diseases, the compounds are still in the early stages of development, most likely due to the complexity of the HIF-1 pathway and their different mechanisms of action for HIF inhibition. Most cancer cells use the glycolytic pathway for energy production and HIF-1alpha participates deeply in the expression of several glycolytic enzymes. Therefore, a detailed study of HIF's function in cancer metabolisms may provide us an alternative strategy for further development of HIF inhibitors in cancer therapy. PMID- 26882241 TI - Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours. AB - OBJECTIVES: The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation. DESIGN: Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n = 10). The donor hearts were perfused at 8 degrees C in cycles of 15 min perfusion followed by 60 min without perfusion. The perfusate consisted of an albumin-containing hyperoncotic cardioplegic nutrition solution with hormones and erythrocytes. Orthotopic transplantation was done in 10 recipient pigs after 24 hours' preservation. Transplanted pigs were monitored for 24 hours, then an adrenaline stress test was done. RESULTS: All transplanted pigs were stable throughout the 24-hour observation period with mean aortic pressure around 80 mmHg and normal urine production. Mean right and left atrial pressures were in the range of 3-6 and 5-10 mmHg, respectively. Blood gases at 24 hours did not differ from baseline values. The adrenaline test showed a dose dependent response, with aortic pressure increasing from 98/70 to 220/150 mmHg and heart rate from 110 to 185 beats/min. CONCLUSION: Orthotopic transplantation of porcine hearts harvested 24 hours after brain death and preserved for 24 hours can be done safely. PMID- 26882242 TI - Differential Effects of Colchicine on Cardiac Cell Viability in an in vitro Model Simulating Myocardial Infarction. AB - OBJECTIVES: We aimed to examine the effects of colchicine, currently in clinical trials for acute myocardial infarction (AMI), on the viability of cardiac cells using a cell line model of AMI. METHODS: HL-1, a murine cardiomyocyte cell line, and H9C2, a rat cardiomyoblast cell line, were incubated with TNFalpha or sera derived from rats that underwent AMI or sham operation followed by addition of colchicine. In another experiment, HL-1/H9C2 cells were exposed to anoxia with or without subsequent addition of colchicine. Cell morphology and viability were assessed by light microscopy, flow cytometry and Western blot analyses for apoptotic markers. RESULTS: Cellular viability was similar in both sera; however, exposing both cell lines to anoxia reduced their viability. Adding colchicine to anoxic H9C2, but not to anoxic HL-1, further increased their mortality, at least in part via enhanced apoptosis. Under any condition, colchicine induced detachment of H9C2 cells from their culture plates. This phenomenon did not apply to HL-1 cells. CONCLUSIONS: Colchicine enhanced cardiomyoblast mortality under in vitro conditions mimicking AMI and reduced their adherence capability. HL-1 was not affected by colchicine; nevertheless, no salvage effect was observed. We thus conclude that colchicine may not inhibit myocardial apoptosis following AMI. PMID- 26882244 TI - Combined Nurr1 and Foxa2 roles in the therapy of Parkinson's disease. PMID- 26882243 TI - Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. AB - DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio suggests a loss of DCC-induced apoptosis, either via a decrease in DCC expression in germinal center subtype or by up-regulation of netrin-1 in activated B-cell (ABC) one. Such imbalance is also observed in mantle cell lymphoma (MCL). Using a netrin-1 interfering antibody, we demonstrate both in vitro and in vivo that netrin-1 acts as a survival factor for ABC-DLBCL and MCL tumor cells. Together, these data suggest that interference with the netrin 1/DCC interaction could represent a promising therapeutic strategy in netrin-1 positive DLBCL and MCL. PMID- 26882245 TI - Homology modeling and molecular dynamics study on Schwanniomyces occidentalis alpha-amylase. AB - With consumers growing increasingly aware of environmental issues, industries find enzymes as a reasonable alternative over physical conditions and chemical catalysts. Amylases are important hydrolase enzymes, which have been widely used in variety of industrial process such as pharmaceutical, food, and fermentation industries. Among amylases alpha-Amylase is in maximum demand due to its wide range of applications. The homology modeling study on Schwanniomyces occidentalis amylase (AMY1, UniProt identifier number: P19269) was performed by Modeller using Aspergillus oryzae (6TAA) as the template. The resulting structure was analyzed for validity and subjected to 14 ns of molecular dynamics (MD) simulation trough GROMACS. The validity of obtained model may represent that utilized OPLS force field is suitable for calcium-containing enzymes. DSSP secondary structure and contact map analysis represent the conservation of domain A TIM barrel feature together with calcium ion coordination sphere. Investigating the covariance matrix followed by principle component analyses for the first five eigenvectors of both trajectories indicate a little more flexibility for AMY1 structure. The electrostatic calculation for the final structures shows similar isoelectric point and superimposed buffering zone in the 5-8 pH range. PMID- 26882246 TI - The First Report of a Pregnancy in a Patient with Purine Nucleoside Phosphorylase Deficiency. AB - BACKGROUND: The cause of primary immunodeficiency has expanded to nearly 200 distinct disorders. An improved understanding of these disorders has resulted in decreased morbidity and mortality with reciprocal improved life expectancy. Obstetricians should have knowledge of primary immunodeficiency, as more women with these disorders will reach reproductive age. CASE: 21-year-old G1P0 with purine nucleoside phosphorylase (PNP) deficiency delivered a viable infant vaginally at 37 weeks. Although the patient's diagnosis and pregnancy placed her at increased risk for infection, she remained asymptomatic and infection-free throughout pregnancy. CONCLUSION: The management of pregnancy complicated by PNP deficiency requires strict immune surveillance and regimented immunoglobulin replacement. PMID- 26882247 TI - [In Process Citation]. PMID- 26882248 TI - Reflections on immunological nomenclature: in praise of imperfection. PMID- 26882249 TI - Fatty acid oxidation in macrophage polarization. PMID- 26882250 TI - Contemplating autoimmunity in the Aegean islands. AB - The Greek island of Crete became host to lively discussions on immunoregulation as experts from around the world gathered for the 7th Aegean Conference on Autoimmunity in September 2015. PMID- 26882251 TI - SHARPINing the knowledge of TCR signal control. PMID- 26882252 TI - The NEK-sus of the NLRP3 inflammasome. PMID- 26882253 TI - A PTENtial cause for the selectivity of oncolytic viruses? PMID- 26882254 TI - Trabid epigenetically drives expression of IL-12 and IL-23. PMID- 26882262 TI - Sample size calculation for testing differences between cure rates with the optimal log-rank test. AB - In this article, sample size calculations are developed for use when the main interest is in the differences between the cure rates of two groups. Following the work of Ewell and Ibrahim, the asymptotic distribution of the weighted log rank test is derived under the local alternative. The optimal log-rank test under the proportional distributions alternative is discussed, and sample size formulas for the optimal and standard log-rank tests are derived. Simulation results show that the proposed formulas provide adequate sample size estimation for trial designs and that the optimal log-rank test is more efficient than the standard log-rank test, particularly when both cure rates and percentages of censoring are small. PMID- 26882261 TI - Inflammatory networks underlying colorectal cancer. AB - Inflammation is emerging as one of the hallmarks of cancer, yet its role in most tumors remains unclear. Whereas a minority of solid tumors are associated with overt inflammation, long-term treatment with non-steroidal anti-inflammatory drugs is remarkably effective in reducing cancer rate and death. This indicates that inflammation might have many as-yet-unrecognized facets, among which an indolent course might be far more prevalent than previously appreciated. In this Review, we explore the various inflammatory processes underlying the development and progression of colorectal cancer and discuss anti-inflammatory means for its prevention and treatment. PMID- 26882263 TI - Testing the functional assessment of mentation: A mobile application based assessment of mental status. AB - BACKGROUND: Altered mental status is a significant predictor of mortality in hospitalized patients and a prerequisite component to the diagnosis of delirium. However, the detection of altered mental status is often incomplete, inaccurate, and resource intensive. OBJECTIVE: To identify the clinical utility and feasibility of the Functional Assessment of Mentation (FAM(TM) ), a mobile application for evaluating attention and recall. DESIGN: Prospective observational pilot study. SETTING: Tertiary care medical center. PARTICIPANTS: Nine hundred thirty-one adult subjects (612 nonhospitalized and 319 hospitalized). MEASUREMENTS: Score distribution and time to FAM(TM) completion were compared between nonhospitalized and hospitalized subjects (as well as between hospitalized subjects discharged home and those not discharged home). Additionally, in the hospitalized subgroup, FAM(TM) was compared to the Glasgow Coma Scale (GCS), using the Short Portable Mental Status Questionnaire (SPMSQ) as our criterion standard for altered mental status assessment. RESULTS: Median time to completion of FAM(TM) was 55 seconds (interquartile range [IQR], 45-67 seconds). Our data identified a graded reduction in score comparing nonhospitalized subjects to hospitalized subjects discharged home and not discharged home (median 5 [IQR 4-7] vs 5 [IQR 3-6] vs 3 [IQR 1-5]; P < 0.001). In the hospitalized subset, FAM(TM) scores were more highly correlated to SPMSQ (Spearman rho = 0.27, P < 0.001) compared to GCS (Spearman rho = 0.05, P = 0.40). CONCLUSIONS: FAM(TM) is a rapid and clinically feasible tool that can identify minor alterations in mental status often missed by GCS. Journal of Hospital Medicine 2016;11:463-466. 2016 Society of Hospital Medicine. PMID- 26882264 TI - Evidence for quorum sensing and differential metabolite production by a marine bacterium in response to DMSP. AB - Microbes, the foundation of the marine foodweb, do not function in isolation, but rather rely on molecular level interactions among species to thrive. Although certain types of interactions between autotrophic and heterotrophic microorganisms have been well documented, the role of specific organic molecules in regulating inter-species relationships and supporting growth are only beginning to be understood. Here, we examine one such interaction by characterizing the metabolic response of a heterotrophic marine bacterium, Ruegeria pomeroyi DSS-3, to growth on dimethylsulfoniopropionate (DMSP), an abundant organosulfur metabolite produced by phytoplankton. When cultivated on DMSP, R. pomeroyi synthesized a quorum-sensing molecule, N-(3-oxotetradecanoyl)-l homoserine lactone, at significantly higher levels than during growth on propionate. Concomitant with the production of a quorum-sensing molecule, we observed differential production of intra- and extracellular metabolites including glutamine, vitamin B2 and biosynthetic intermediates of cyclic amino acids. Our metabolomics data indicate that R. pomeroyi changes regulation of its biochemical pathways in a manner that is adaptive for a cooperative lifestyle in the presence of DMSP, in anticipation of phytoplankton-derived nutrients and higher microbial density. This behavior is likely to occur on sinking marine particles, indicating that this response may impact the fate of organic matter. PMID- 26882265 TI - The bacterial microbiome of Dermacentor andersoni ticks influences pathogen susceptibility. AB - Ticks are of medical importance owing to their ability to transmit pathogens to humans and animals. The Rocky Mountain wood tick, Dermacentor andersoni, is a vector of a number of pathogens, including Anaplasma marginale, which is the most widespread tick-borne pathogen of livestock. Although ticks host pathogenic bacteria, they also harbor bacterial endosymbionts that have a role in tick physiology, survival, as well as pathogen acquisition and transmission. The goal of this study was to characterize the bacterial microbiome and examine the impact of microbiome disruption on pathogen susceptibility. The bacterial microbiome of two populations of D. andersoni with historically different susceptibilities to A. marginale was characterized. In this study, the microbiome was disrupted and then ticks were exposed to A. marginale or Francisella novicida to determine whether the microbiome correlated with pathogen susceptibility. Our study showed that an increase in proportion and quantity of Rickettsia bellii in the microbiome was negatively correlated to A. marginale levels in ticks. Furthermore, a decrease in Francisella endosymbionts was associated with lower F. novicida infection levels, demonstrating a positive pathogen-endosymbiont relationship. We demonstrate that endosymbionts and pathogens have varying interactions, and suggest that microbiome manipulation may provide a possible method for biocontrol by decreasing pathogen susceptibility of ticks. PMID- 26882266 TI - High coverage metabolomics analysis reveals phage-specific alterations to Pseudomonas aeruginosa physiology during infection. AB - Phage-mediated metabolic changes in bacteria are hypothesized to markedly alter global nutrient and biogeochemical cycles. Despite their theoretic importance, experimental data on the net metabolic impact of phage infection on the bacterial metabolism remains scarce. In this study, we tracked the dynamics of intracellular metabolites using untargeted high coverage metabolomics in Pseudomonas aeruginosa cells infected with lytic bacteriophages from six distinct phage genera. Analysis of the metabolomics data indicates an active interference in the host metabolism. In general, phages elicit an increase in pyrimidine and nucleotide sugar metabolism. Furthermore, clear phage-specific and infection stage-specific responses are observed, ranging from extreme metabolite depletion (for example, phage YuA) to complete reorganization of the metabolism (for example, phage phiKZ). As expected, pathways targeted by the phage-encoded auxiliary metabolic genes (AMGs) were enriched among the metabolites changing during infection. The effect on pyrimidine metabolism of phages encoding AMGs capable of host genome degradation (for example, YuA and LUZ19) was distinct from those lacking nuclease-encoding genes (for example, phiKZ), which demonstrates the link between the encoded set of AMGs of a phage and its impact on host physiology. However, a large fraction of the profound effect on host metabolism could not be attributed to the phage-encoded AMGs. We suggest a potentially crucial role for small, 'non-enzymatic' peptides in metabolism take-over and hypothesize on potential biotechnical applications for such peptides. The highly phage-specific nature of the metabolic impact emphasizes the potential importance of the 'phage diversity' parameter when studying metabolic interactions in complex communities. PMID- 26882267 TI - Pathways and key intermediates required for obligate aerobic ammonia-dependent chemolithotrophy in bacteria and Thaumarchaeota. AB - Chemolithotrophic ammonia-oxidizing bacteria and Thaumarchaeota are central players in the global nitrogen cycle. Obligate ammonia chemolithotrophy has been characterized for bacteria; however, large gaps remain in the Thaumarchaeotal pathway. Using batch growth experiments and instantaneous microrespirometry measurements of resting biomass, we show that the terrestrial Thaumarchaeon Nitrososphaera viennensis EN76(T) exhibits tight control over production and consumption of nitric oxide (NO) during ammonia catabolism, unlike the ammonia oxidizing bacterium Nitrosospira multiformis ATCC 25196(T). In particular, pulses of hydroxylamine into a microelectrode chamber as the sole substrate for N. viennensis resulted in iterative production and consumption of NO followed by conversion of hydroxylamine to nitrite. In support of these observations, oxidation of ammonia in growing cultures of N. viennensis, but not of N. multiformis, was inhibited by the NO-scavenger PTIO. When based on the marginal nitrous oxide (N2O) levels detected in cell-free media controls, the higher levels produced by N. multiformis were explained by enzyme activity, whereas N2O in N. viennensis cultures was attributed to abiotic reactions of released N-oxide intermediates with media components. Our results are conceptualized in a pathway for ammonia-dependent chemolithotrophy in Thaumarchaea, which identifies NO as an essential intermediate in the pathway and implements known biochemistry to be executed by a proposed but still elusive copper enzyme. Taken together, this work identifies differences in ammonia-dependent chemolithotrophy between bacteria and the Thaumarchaeota, advances a central catabolic role of NO only in the Thaumarchaeotal pathway and reveals stark differences in how the two microbial cohorts contribute to N2O emissions. PMID- 26882268 TI - Microbial community modeling using reliability theory. AB - Linking microbial community composition with the corresponding ecosystem functions remains challenging. Because microbial communities can differ in their functional responses, this knowledge gap limits ecosystem assessment, design and management. To develop models that explicitly incorporate microbial populations and guide efforts to characterize their functional differences, we propose a novel approach derived from reliability engineering. This reliability modeling approach is illustrated here using a microbial ecology dataset from denitrifying bioreactors. Reliability modeling is well-suited for analyzing the stability of complex networks composed of many microbial populations. It could also be applied to evaluate the redundancy within a particular biochemical pathway in a microbial community. Reliability modeling allows characterization of the system's resilience and identification of failure-prone functional groups or biochemical steps, which can then be targeted for monitoring or enhancement. The reliability engineering approach provides a new perspective for unraveling the interactions between microbial community diversity, functional redundancy and ecosystem services, as well as practical tools for the design and management of engineered ecosystems. PMID- 26882269 TI - Bacterial communities from Arctic seasonal sea ice are more compositionally variable than those from multi-year sea ice. AB - Arctic sea ice can be classified into two types: seasonal ice (first-year ice, FYI) and multi-year ice (MYI). Despite striking differences in the physical and chemical characteristics of FYI and MYI, and the key role sea ice bacteria play in biogeochemical cycles of the Arctic Ocean, there are a limited number of studies comparing the bacterial communities from these two ice types. Here, we compare the membership and composition of bacterial communities from FYI and MYI sampled north of Ellesmere Island, Canada. Our results show that communities from both ice types were dominated by similar class-level phylogenetic groups. However, at the operational taxonomic unit (OTU) level, communities from MYI and FYI differed in both membership and composition. Communities from MYI sites had consistent structure, with similar membership (presence/absence) and composition (OTU abundance) independent of location and year of sample. By contrast, communities from FYI were more variable. Although FYI bacterial communities from different locations and different years shared similar membership, they varied significantly in composition. Should these findings apply to sea ice across the Arctic, we predict increased compositional variability in sea ice bacterial communities resulting from the ongoing transition from predominantly MYI to FYI, which may impact nutrient dynamics in the Arctic Ocean. PMID- 26882270 TI - Cranial nerve palsy secondary to cerebrospinal fluid diversion. AB - OBJECTIVE: Cranial nerve palsy (CNP) secondary to cerebrospinal fluid (CSF) diversion is less familiar to us as a result of its rarity in incidence and insidiousness in presentation. This study aims to further expound the pathophysiological mechanism, clinical presentation, diagnosis, management and prognosis of CNP. METHODS: From June 2012 to February 2015, 5 of 347 consecutive patients with CNPs secondary to different CSF diversion procedures were treated at our institution. A systematic PubMed search of published studies written in English for patients developing CNPs after CSF diversion procedures from January 1950 to June 2015 was conducted. RESULTS: Overall, 29 studies and 5 patients of the current series totaling 53 CNPs met the inclusion criteria. CN II, III, IV, V, VI, VII and VIII were got involved in 2 (3.8%), 2 (3.8%), 5 (9.4%), 1 (1.9%), 44 (83.0%), 4 (7.5%) and 1 (1.9%) patients respectively. Thirty-eight patients (71.7%) developed CNPs following inadvertent lumbar puncture, 8 (15.1%) following lumbar drainage, and 7 (13.2%) following ventriculoperitoneal shunt. Forty-eight (90.6%) patients got resolved completely. CONCLUSIONS: The proposed mechanism of CNP after CSF diversion procedure is CSF hypovolemia and subsequent downward displacement of the brain and traction and distortion of the vascular and peripheral neural structures. As a result of its distinct anatomic characteristics rather than long intracranial course, CN VI is most commonly affected. With early recognition and timely conservative management, most patients could get favorable recovery. PMID- 26882271 TI - Bronchiectasis in China. AB - Bronchiectasis is a common but long-neglected disease in China, causing a substantial disease burden both to patients and to society. The overall prevalence of physician-diagnosed bronchiectasis in people aged 40 years or older is estimated at 1.2% and is trending upward with aging of the population. The etiology of bronchiectasis has not been identified heretofore in more than 70% of patients in China, although pneumonia and tuberculosis still appear to be the most common causes of acquired bronchiectasis. Etiologies, comorbidities, and infecting organisms vary greatly across previously published epidemiological studies, resulting in considerable uncertainty. Little is known about the spectrum of severity of bronchiectasis in China. Presently, engagement of pulmonologists is largely limited to acute treatment of exacerbations of severe bronchiectasis. Based on limited available data and expert consensus, the first comprehensive guidelines for the diagnosis and treatment of bronchiectasis in China were published in 2012. Research to advance medical care for patients with this disease in China should focus on several priorities, including: standardization of diagnostic criteria with appropriate application of computed tomographic imaging; use of validated multidimensional grading systems to assess the severity of bronchiectasis; and epidemiological studies that are designed to measure mild to moderate as well as severe disease, and to represent the population beyond large urban centers. Better estimates of the true burden of bronchiectasis are needed to guide allocation of national medical resources and to implement public health strategies for prevention of the disease. Treatment should be expanded to include expert maintenance care of ambulatory patients in addition to treatment of exacerbations. PMID- 26882272 TI - Periprocedural Management of Direct Oral Anticoagulants: Comment on the 2015 American Society of Regional Anesthesia and Pain Medicine Guidelines. PMID- 26882275 TI - Internal conversion and intersystem crossing in alpha,beta-enones: a combination of electronic structure calculations and dynamics simulations. AB - The ab initio electronic structure calculations and CASSCF-based nonadiabatic dynamics simulations have been used to investigate the internal conversion and intersystem crossing process of both trans-acrolein and 2-cyclopentenone in the gas phase. Our calculation results show that relaxation from the Franck-Condon region to an S1 minimum is ultrafast and that the S1 state will dominantly undergo intersystem crossing to triplet states due to the existence of significant barriers to access the S1/S0 intersection points and of energetically close-lying triplet states. The S1/T2/T1 three-state intersection is observed in our dynamics simulations to play an important role in the population of the lowest triplet state, which is consistent with previous suggestions. Although the evolution into triplet states involves a similar path and gives rise to a similar triplet quantum yield for these two molecules, the intersystem crossing rate of 2 cyclopentenone is lower owing to the ring constraint that results in a smaller spin-orbital coupling in the singlet-triplet crossing region. The present theoretical study reproduces the experimental results and gives an explanation about the structural factors that govern the excited-state decay of some types of alpha,beta-enones. PMID- 26882276 TI - Lung Cancer Risk from Radon in Marcellus Shale Gas in Northeast U.S. Homes. AB - The amount of radon in natural gas varies with its source. Little has been published about the radon from shale gas to date, making estimates of its impact on radon-induced lung cancer speculative. We measured radon in natural gas pipelines carrying gas from the Marcellus Shale in Pennsylvania and West Virginia. Radon concentrations ranged from 1,520 to 2,750 Bq/m3 (41-74 pCi/L), and the throughput-weighted average was 1,983 Bq/m3 (54 pCi/L). Potential radon exposure due to the use of Marcellus Shale gas for cooking and space heating using vent-free heaters or gas ranges in northeastern U.S. homes and apartments was assessed. Though the measured radon concentrations are higher than what has been previously reported, it is unlikely that exposure from natural gas cooking would exceed 1.2 Bq/m3 (<1% of the U.S. Environmental Protection Agency's action level). Using worst-case assumptions, we estimate the excess lifetime (70 years) lung cancer risk associated with cooking to be 1.8*10-4 (interval spanning 95% of simulation results: 8.5*10-5 , 3.4*10-4 ). The risk profile for supplemental heating with unvented gas appliances is similar. Individuals using unvented gas appliances to provide primary heating may face lifetime risks as high as 3.9*10-3 . Under current housing stock and gas consumption assumptions, expected levels of residential radon exposure due to unvented combustion of Marcellus Shale natural gas in the Northeast United States do not result in a detectable change in the lung cancer death rates. PMID- 26882277 TI - Why It's Important to Continue Universal Autism Screening While Research Fully Examines Its Impact. PMID- 26882278 TI - Editorial: Can an Increase in Antineutrophil Cytoplasmic Autoantibody Titer Predict Relapses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis? PMID- 26882279 TI - Crystallinity-dependence of ionic conductivity in the ion pairs of a multi interactive anion. AB - Ammonium and sodium salts (ion pairs) of a multi-interactive tri(4 pyridyl)hexaazaphenalenyl anion (TPHAP(-)) showed completely different ion conductive properties depending on the crystal structure. TPHAP columnar crystals showed a high conductivity of 10(-3) S cm(-1) while retaining their structures even under humid conditions, whereas TPHAP dimer crystals exhibited a conductivity of ~10(-5) S cm(-1) with crystallinity deterioration. The main unit structures induced by multi-interactivity realized different water accessibility, which explains the differences in their ion conductivity and stability against humidity. PMID- 26882280 TI - Organocatalytic Asymmetric Synthesis of Dihydrobenzoxazinones Bearing Trifluoromethylated Quaternary Stereocenters. AB - Chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of trifluoromethyl benzoxazinones with pyrroles is reported. Under mild conditions, a range of enantioenriched dihydrobenzoxazinones bearing trifluoromethylated quaternary stereocenters could be obtained in good to excellent yield and ee. A remarkable fluorine effect is observed, and preliminary mechanistic studies combined with theory calculations suggest that triple-hydrogen-bonding interactions hold the transition structure rigidly and allow the bulky substituents of the catalyst to influence the enantioselectivity. PMID- 26882281 TI - Examining Nock and Prinstein's four-function model with offenders who self injure. AB - Nonsuicidal self-injury (NSSI) is the deliberate bodily harm or disfigurement without suicidal intent and for purposes not socially sanctioned (e.g., cutting, burning, head banging). Nock and Prinstein (2004) proposed a 4-function model (FFM) of NSSI, in which the functions of NSSI are categorized by two dichotomous factors: (a) positive (i.e., involves the addition of a favorable stimulus) or negative (i.e., involves the removal of an aversive stimulus; and (b) automatic (i.e., intrapersonal) or social (i.e., interpersonal). This study examined the validity of this model with incarcerated populations. In-depth semistructured interviews with 201 incarcerated offenders were analyzed and categorized based on the FFM. Participants' descriptions of functions of NSSI were most commonly categorized as automatic negative reinforcement (25.0%; e.g., coping with negative emotions), followed by automatic positive reinforcement (31.3%; e.g., self-punishment), social positive reinforcement (31.3%; e.g., to communicate with others), and social negative reinforcement (12.5%; e.g., to avoid hurting someone else). While the uniqueness of the correctional environment affects some of the specific functions evident in offenders, FFM can be used to adequately organize the functions of NSSI in offenders, providing a useful tool for explaining this complex behavior. Clinically, NSSI in offenders can be viewed has having the same underlying motivations, although automatic positive reinforcement is more prevalent in offenders and social positive reinforcement is more prevalence in nonoffenders. Given that the motivations underlying nonsuicidal self-injury are similar for offender and nonoffender populations, similar treatment approaches may be effective with both populations. (PsycINFO Database Record PMID- 26882282 TI - The specificity of emotional switching in borderline personality disorder in comparison to other clinical groups. AB - In an attempt to better understand the nature of emotion dysregulation in the daily lives of persons with a borderline personality disorder (BPD), Houben et al. (2016) recently identified emotional switching, which refers to the tendency to make large changes between positive and negative emotional states over time, as a possible defining characteristic of the emotion dynamics observed in BPD. The goal of this study was to examine the specificity of these previous findings in 2 samples by comparing BPD patients (N = 43 in sample 1; N = 81 in sample 2) to patients with bulimia nervosa (N = 20), posttraumatic stress disorder (N = 28), or healthy controls (N = 28) in sample 1, and to patients with depressive disorder (N = 50) in sample 2, with respect to measures of emotional switching. Analyses of these 2 experience sampling datasets revealed that contrary to expectations, BPD patients did not differ from the clinical groups regarding their mere tendency to switch between positive and negative emotional states on consecutive moments over time and regarding the magnitude of such changes between positive and negative emotional states over time. However, all clinical groups did differ from healthy controls regarding all switch measures in dataset 1. These results indicate that emotional switching, similar to other more traditional indicators of overall changes in emotional intensity in daily life, might reflect a feature of emotional responding characterizing a range of disorders with mood disturbances. PMID- 26882283 TI - Fluorescent Nanodiamond: A Versatile Tool for Long-Term Cell Tracking, Super Resolution Imaging, and Nanoscale Temperature Sensing. AB - Fluorescent nanodiamond (FND) has recently played a central role in fueling new discoveries in interdisciplinary fields spanning biology, chemistry, physics, and materials sciences. The nanoparticle is unique in that it contains a high density ensemble of negatively charged nitrogen-vacancy (NV(-)) centers as built-in fluorophores. The center possesses a number of outstanding optical and magnetic properties. First, NV(-) has an absorption maximum at ~550 nm, and when exposed to green-orange light, it emits bright fluorescence at ~700 nm with a lifetime of longer than 10 ns. These spectroscopic properties are little affected by surface modification but are distinctly different from those of cell autofluorescence and thus enable background-free imaging of FNDs in tissue sections. Such characteristics together with its excellent biocompatibility render FND ideal for long-term cell tracking applications, particularly in stem cell research. Next, as an artificial atom in the solid state, the NV(-) center is perfectly photostable, without photobleaching and blinking. Therefore, the NV-containing FND is suitable as a contrast agent for super-resolution imaging by stimulated emission depletion (STED). An improvement of the spatial resolution by 20-fold is readily achievable by using a high-power STED laser to deplete the NV(-) fluorescence. Such improvement is crucial in revealing the detailed structures of biological complexes and assemblies, including cellular organelles and subcellular compartments. Further enhancement of the resolution for live cell imaging is possible by manipulating the charge states of the NV centers. As the "brightest" member of the nanocarbon family, FND holds great promise and potential for bioimaging with unprecedented resolution and precision. Lastly, the NV(-) center in diamond is an atom-like quantum system with a total electron spin of 1. The ground states of the spins show a crystal field splitting of 2.87 GHz, separating the ms = 0 and +/-1 sublevels. Interestingly, the transitions between the spin sublevels can be optically detected and manipulated by microwave radiation, a technique known as optically detected magnetic resonance (ODMR). In addition, the electron spins have an exceptionally long coherence time, making FND useful for ultrasensitive detection of temperature at the nanoscale. Pump probe-type nanothermometry with a temporal resolution of better than 10 MUs has been achieved with a three-point sampling method. Gold/diamond nanohybrids have also been developed for highly localized hyperthermia applications. This Account provides a summary of the recent advances in FND-enabled technologies with a special focus on long-term cell tracking, super-resolution imaging, and nanoscale temperature sensing. These emerging and multifaceted technologies are in synchronicity with modern imaging modalities. PMID- 26882284 TI - Jagn1 Is Induced in Response to ER Stress and Regulates Proinsulin Biosynthesis. AB - The Jagn1 protein was indentified in a SILAC proteomic screen of proteins that are increased in insulinoma cells expressing a folding-deficient proinsulin. Jagn1 mRNA was detected in primary rodent islets and in insulinoma cell lines and the levels were increased in response to ER stress. The function of Jagn1 was assessed in insulinoma cells by both knock-down and overexpression approaches. Knock-down of Jagn1 caused an increase in glucose-stimulated insulin secretion resulting from an increase in proinsulin biosynthesis. In contrast, overexpression of Jagn1 in insulinoma cells resulted in reduced cellular proinsulin and insulin levels. Our results identify a novel role for Jagn1 in regulating proinsulin biosynthesis in pancreatic beta-cells. Under ER stress conditions Jagn1 is induced which might contribute to reducing proinsulin biosynthesis, in part by helping to relieve the protein folding load in the ER in an effort to restore ER homeostasis. PMID- 26882285 TI - Potential relationship of self-injurious behavior to right temporo-parietal lesions. AB - Self-injurious behavior (SIB) is associated with several neurologic and psychiatric syndromes but rarely with focal lesions. Two patients with lesions of the right temporo-parietal junction presented to psychiatric inpatient services with SIB in the absence of notable neurologic deficits or suicidal ideation. Right temporo-parietal lesions may be associated with disturbances of agency and body ownership, both of which may facilitate SIB. Misoplegia, or hatred of a limb, may be associated with SIB and has been reported without hemiplegia with a right temporo-parietal lesion. Further study is warranted to improve our understanding of the mechanisms underlying SIB. PMID- 26882286 TI - Individual differences in working-memory capacity and task resumption following interruptions. AB - Previous research has shown that there is a time cost (i.e., a resumption lag) associated with resuming a task following an interruption and that the longer the duration of the interruption, the greater the time cost (i.e., resumption lag increases as interruption duration increases). The memory-for-goals model (Altmann & Trafton, 2002) suggests that this greater time cost is a result of increased interference caused by longer duration interruptions. Therefore, the goal for this research was to determine whether individuals who can better manage interference, i.e., individuals with higher working-memory capacity (WMC), can resume tasks more quickly following interruptions than those who cannot manage interference as well (i.e., individuals with lower WMC). A procedural interruption task with 3 different interruption durations and a measure of WMC were completed by 229 students. In line with previous research, we found a strong positive relationship between interruption duration and resumption lag. We found a strong negative effect of WMC on resumption lag (i.e., increases in WMC reduced resumption lags). Notably, WMC moderated the effect of interruption duration on resumption lag (i.e., increases in WMC attenuated the positive relationship between interruption duration and resumption lag). Specifically, individuals with high WMC experienced small increases in resumption lag as interruption duration increased, whereas individuals with low WMC experienced substantial increases in resumption lag as interruption duration increased. Our data suggest that individuals with higher WMC are less susceptible to interference caused by interruptions. (PsycINFO Database Record PMID- 26882287 TI - Usefulness of translocation-associated immunohistochemical stains in the fine needle aspiration diagnosis of salivary gland neoplasms. AB - BACKGROUND: Fine-needle aspiration diagnosis of pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) is challenging due to cytologic overlap with one another and with other salivary gland tumors having prominent epithelial and myoepithelial components. Recognition of characteristic chromosomal aberrations in several salivary gland tumors, including PA and ACC, has the potential to resolve diagnostic uncertainty, but molecular diagnostics are not routinely available. To leverage these molecular alterations, the authors examined a panel of commercially available immunostains directed at commonly overexpressed proteins in translocation-associated PA (PLAG1 and HMGA2) and ACC (MYB) to assess their diagnostic usefulness. METHODS: Immunohistochemistry was performed on cell block samples from 74 patients, including 11 ACC specimens and 31 PA specimens with antibodies to MYB, PLAG1, and HMGA2 as well as KIT (previously considered useful in the diagnosis of ACC). RESULTS: ACCs demonstrated significantly greater staining for KIT compared with non-ACCs, while PAs had significantly greater staining for PLAG1 than non-PAs. MYB trended toward significance for ACC (P=.097) and HMGA2 trended toward significance for PA (P=.094). No ACC exhibited positive staining for PLAG1 or HMGA2. Only 12% of PAs were found to be positive for MYB or KIT. Combined positivity for MYB and KIT with negative PLAG1 and HMGA2 demonstrated a specificity and positive predictive value of 1.0 for ACC, whereas a positive PLAG1 or HMGA2 stain with negative MYB and KIT stains showed a sensitivity of 0.75, a specificity of 0.96, and a positive predictive value of 0.95 for PAs. CONCLUSIONS: An immunohistochemical panel of MYB, KIT, PLAG1, and HMGA2 on fine-needle aspiration cell blocks is useful in distinguishing ACCs and PAs from each other and other salivary gland neoplasms. Cancer Cytopathol 2016;124:397-405. (c) 2016 American Cancer Society. PMID- 26882288 TI - Challenges and Perspectives on the Development of Small-Molecule EGFR Inhibitors against T790M-Mediated Resistance in Non-Small-Cell Lung Cancer. AB - Because of the development of drug-resistance mutations, particularly the "gatekeeper" threonine(790)-to-methionine(790) (T790M) mutation in the ATP binding pocket of the epidermal growth factor receptor (EGFR), the current generation of EGFR tyrosine kinase inhibitors lost their clinical efficacy. Recently, a large number of small-molecule inhibitors with striking inhibitory potency against EGFR mutants with the T790M change have been identified. In particular, the inhibitors rociletinib and osimertinib, which can selectively target both sensitizing mutations and the T790M resistance while sparing the wild type (WT) form of the receptor, have been designated as breakthrough therapies in the treatment of mutant non-small-cell lung cancer (NSCLC) by the U.S. FDA in 2014. We hope that this review on the small-molecule EGFR T790M inhibitors, along with their discovery strategies, will assist in the design of future T790M containing EGFR inhibitors with high levels of selectivity over WT EGFR, broad kinase selectivity, and desirable physicochemical properties. PMID- 26882289 TI - Methanol-Triggered Turn-On-Type Photoluminescence in L-Cysteinato Palladium(II) and Platinum(II) Complexes Supported by a Bis(diphenylphosphine) Ligand. AB - The selective detection of methanol by photoluminescence under environmental conditions has been a great challenge for materials science. Herein, a reversible, turn-on-type photoluminescence triggered by methanol vapor in square planar palladium(II) and platinum(II) complexes, newly prepared from [MCl2(1,3 bis(diphenylphosphino)propane)] and L-cysteine, is reported. Both the "turn-on" and "turn-off" states of the complexes were crystallographically characterized, which revealed the presence of intermolecular OH...O and CH...pi interactions between methanol and the complex molecules in the turn-on state. These interactions prevent the vibrational quenching of the luminescence, leading to the turn-on-type luminescence in this system. PMID- 26882290 TI - Investigation of DNA binding, DNA photocleavage, topoisomerase I inhibition and antioxidant activities of water soluble titanium(IV) phthalocyanine compounds. AB - The binding mode of water soluble peripherally tetra-substituted titanium(IV) phthalocyanine (Pc) compounds Pc1, Pc2 and Pc3 with calf thymus (CT) DNA was investigated by using UV-Vis spectroscopy and thermal denaturation studies in this work. The results of DNA binding constants (Kb) and the changes in the thermal denaturation profile of DNA with the addition of Pc compounds indicated that Pc1, Pc2 and Pc3 are able to bind to CT-DNA with different binding affinities. DNA photocleavage studies of Pc compounds were performed in the absence and presence of oxidizing agents such as hydrogen peroxide (H2O2), ascorbic acid (AA) and 2-mercaptoethanol (ME) using the agarose gel electrophoresis method at irradiation 650 nm. According to the results of electrophoresis studies, Pc1, Pc2 and Pc3 cleaved of supercoiled pBR322 DNA via photocleavage pathway. The Pc1, Pc2 and Pc3 compounds were examined for topoisomerase I inhibition by measuring the relaxation of supercoiled pBR322 DNA. The all of Pc compounds inhibited topoisomerase I at 20 MUM concentration. A series of antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radical scavenging (SOD) assay and metal chelating effect assay were performed for Pc1, Pc2 and Pc3 compounds. The results of antioxidant assays indicated that Pc1, Pc2 and Pc3 compounds have remarkable superoxide radical scavenging activities, moderate 2,2-diphenyl-1-picrylhydrazyl activities and metal chelating effect activities. All the experimental studies showed that Pc1, Pc2 and Pc3 compounds bind to CT-DNA via minor groove binding, cleave of supercoiled pBR322 DNA via photocleavage pathway, inhibit topoisomerase I and have remarkable superoxide radical scavenging activities. Thanks to these properties the Pc1, Pc2 and Pc3 compounds are suitable agents for photo dynamic therapy. PMID- 26882292 TI - Error in Funding/Support. PMID- 26882291 TI - Pharmacophore hybrid approach of new modulated bis-diimine Cu(II)/Zn(II) complexes based on 5-chloro Isatin Schiff base derivatives: Synthesis, spectral studies and comparative biological assessment. AB - Novel bioactive 5-chloro isatin based Schiff base ligands, (N,N'E,N,N'Z)-N,N'-(5 chloroindoline-2,3-diylidene)bis(5-nitrobenzo [d]thiazol-2-amine), L(1) and (N,N'E,N,N'Z)-N,N'-(5-chloroindoline-2,3-diylidene)bis(5-nitrothiazol-2-amine), L(2) derived from 2-amino 5-nitrobenzothiazole and 2-amino 5-nitrothiazole and their metal complexes, [Cu(L(1))2]Cl2;1, [Zn(L(1))2(H2O)2]Cl2;2, [Cu(L(2))2]Cl2;3 and [Zn(L(2))2(H2O)2]Cl2;4 have been synthesized. The composition, stoichiometry and geometry of the proposed ligands and their complexes have been envisaged by the results of elemental analyses and spectroscopic data (FT-IR, (1)H NMR and (13)C NMR, Mass and EPR). The molar conductivity values of the metal complexes revealed their ionic nature. The thermal stability of metal complexes was demonstrated by TGA/DTA studies while the crystalline nature of the complexes has been ascertained by XRD. Furthermore, a comparative account of in vitro antibacterial study against different bacterial strains with respect to standard antibiotic and scavenging activity against standard control at different concenterations unfolded pronounced antibacterial and radical scavenging potencies of the metal complexes as compared to free ligands. In addition, in vitro cytotoxicity of ligands and its metal complexes was also screened on MCF7 (Human breast adenocarcinoma), HeLa (Human cervical carcinoma) and HepG2 (Human Hepatocellular carcinoma), cell lines and normal cells (PBMC). The antiproliferative outcomes revealed that metal complexes exhibit superior activity in general as compared to free ligands (L(1) and L(2)) where metal complexes (1 and 2) of 5-chloro isatin linked benzothiazole motif (L(1)) are found to have better prospect of acting as chemotherapeutic agents which can be explained in terms of greater biopotency, planarity and conjugation against all the tested cancer cell lines with IC50<2.80 MUM. PMID- 26882293 TI - SYMPTOM BENCHMARKS OF IMPROVED QUALITY OF LIFE IN PTSD. AB - BACKGROUND: Although research has shown that PTSD symptom change relates to improved quality of life, the question of how much improvement in PTSD symptoms is necessary to result in meaningful improvements in quality of life remains unanswered. We used data from a randomized clinical trial of psychotherapy for PTSD in female military veterans and active duty personnel to examine the correspondence between benchmarks of improvement in PTSD symptoms and changes in quality of life. METHODS: Participants were 235 female veterans and Army soldiers who were randomized to 10 weekly sessions of Prolonged Exposure or Present Centered Therapy. We operationalized PTSD symptom change in terms of four progressively stringent mutually exclusive definitions-No Response, Response, Loss of Diagnosis, and Remission-successively comparing each category to the prior one: No Response versus Response, Response versus Loss of Diagnosis, and Loss of Diagnosis versus Remission. Outcomes were clinically meaningful improvements and good endpoints in domains of clinician-rated and self-reported quality of life. RESULTS: Response was associated with improvement on almost all measures, but with only one good endpoint. Loss of Diagnosis was associated with improvement on all measures except self-rated social functioning and with achieving a good endpoint on all measures. Remission was associated with improvement in clinician-rated social impairment and a good endpoint in clinician rated occupational impairment. CONCLUSIONS: For most domains of quality of life, treating a patient until the patient no longer meets diagnostic criteria would be optimal. For some domains, further improvements may result by helping a patient achieve remission. PMID- 26882294 TI - Spectral and Dynamical Properties of Single Excitons, Biexcitons, and Trions in Cesium-Lead-Halide Perovskite Quantum Dots. AB - Organic-inorganic lead-halide perovskites have been the subject of recent intense interest due to their unusually strong photovoltaic performance. A new addition to the perovskite family is all-inorganic Cs-Pb-halide perovskite nanocrystals, or quantum dots, fabricated via a moderate-temperature colloidal synthesis. While being only recently introduced to the research community, these nanomaterials have already shown promise for a range of applications from color-converting phosphors and light-emitting diodes to lasers, and even room-temperature single photon sources. Knowledge of the optical properties of perovskite quantum dots still remains vastly incomplete. Here we apply various time-resolved spectroscopic techniques to conduct a comprehensive study of spectral and dynamical characteristics of single- and multiexciton states in CsPbX3 nanocrystals with X being either Br, I, or their mixture. Specifically, we measure exciton radiative lifetimes, absorption cross-sections, and derive the degeneracies of the band-edge electron and hole states. We also characterize the rates of intraband cooling and nonradiative Auger recombination and evaluate the strength of exciton-exciton coupling. The overall conclusion of this work is that spectroscopic properties of Cs-Pb-halide quantum dots are largely similar to those of quantum dots of more traditional semiconductors such as CdSe and PbSe. At the same time, we observe some distinctions including, for example, an appreciable effect of the halide identity on radiative lifetimes, considerably shorter biexciton Auger lifetimes, and apparent deviation of their size dependence from the "universal volume scaling" previously observed for many traditional nanocrystal systems. The high efficiency of Auger decay in perovskite quantum dots is detrimental to their prospective applications in light-emitting devices and lasers. This points toward the need for the development of approaches for effective suppression of Auger recombination in these nanomaterials, using perhaps insights gained from previous studies of II-VI nanocrystals. PMID- 26882295 TI - Synthesis and Multibromination of Nanosized Helical Aromatic Amide Foldamers via Segment-Doubling Condensation. AB - The synthesis of very long helical aromatic amide foldamers was thought to be limited by steric hindrance associated with stable folded conformations. This difficulty may be overcome by using pure reagents, relatively high concentrations, and long reaction times. Bromine substituents and careful identification and elimination of anhydride byproducts both greatly improve chromatographic purification, giving access to pure products amenable to a segment-doubling synthesis of sequences composed of up to 96 monomers. An efficient one-pot multibromination of helical oligomers is also reported. PMID- 26882296 TI - Neuroprotective effect of melatonin in experimental optic neuritis in rats. AB - Optic neuritis (ON) is an inflammatory, demyelinating, and neurodegenerative condition of the optic nerve, which might induce permanent vision loss. Currently, there are no effective therapies for this disorder. We have developed an experimental model of primary ON in rats through a single microinjection of 4.5 MUg of bacterial lipopolysaccharide (LPS) into the optic nerve. Since melatonin acts as a pleiotropic therapeutic agent in various neurodegenerative diseases, we analyzed the effect of melatonin on LPS-induced ON. For this purpose, LPS or vehicle were injected into the optic nerve from adult male Wistar rats. One group of animals received a subcutaneous pellet of 20 mg melatonin at 24 hr before vehicle or LPS injection, and another group was submitted to a sham procedure. Melatonin completely prevented the decrease in visual evoked potentials (VEPs), and pupil light reflex (PLR), and preserved anterograde transport of cholera toxin beta-subunit from the retina to the superior colliculus. Moreover, melatonin prevented microglial reactivity (ED1 immunoreactivity, P < 0.01), astrocytosis (glial fibrillary acid protein immunostaining, P < 0.05), demyelination (luxol fast blue staining, P < 0.01), and axon (toluidine blue staining, P < 0.01) and retinal ganglion cell (Brn3a immunoreactivity, P < 0.01) loss, induced by LPS. Melatonin completely prevented the increase in nitric oxide synthase 2, cyclooxygenase-2 levels (Western blot) and TNFalpha levels, and partly prevented lipid peroxidation induced by experimental ON. When the pellet of melatonin was implanted at 4 days postinjection of LPS, it completely reversed the decrease in VEPs and PLR. These data suggest that melatonin could be a promising candidate for ON treatment. PMID- 26882297 TI - Web Exclusives. The Consult Guys--CHADS, SHMADS: What's All This About Anticoagulation? PMID- 26882299 TI - ACP Journal Club. Review: More- vs less-intensive BP-lowering regimens reduce major CV events. PMID- 26882300 TI - ACP Journal Club. In patients with SBP >= 130 mm Hg and CV risk, intensive vs standard BP control reduced CV events and mortality. PMID- 26882301 TI - ACP Journal Club. In resistant hypertension, add-on spironolactone reduced SBP more than placebo, doxazosin, or bisoprolol over 12 wk. PMID- 26882302 TI - ACP Journal Club. In abstinent adults with type 2 diabetes, a daily glass of wine (vs mineral water) improved cardiometabolic factors. PMID- 26882303 TI - ACP Journal Club. In high-risk patients, oral nicotinamide reduced number of new nonmelanoma skin cancers during treatment. PMID- 26882304 TI - ACP Journal Club. In acute low back pain, adding oxycodone/acetaminophen or cyclobenzaprine to naproxen did not improve pain or function. PMID- 26882305 TI - ACP Journal Club. Review: In rheumatoid arthritis, TNF-alpha inhibitors do not differ from placebo or DMARDs for all-cause mortality. PMID- 26882306 TI - ACP Journal Club. In patients with hypertension, beta-blockers in the 120 d before noncardiac surgery were linked to CV events and death. PMID- 26882307 TI - ACP Journal Club. Some risk scores plus high-sensitivity troponin may identify patients with chest pain for early discharge. PMID- 26882308 TI - ACP Journal Club. In atrial fibrillation, the ATRIA risk score better predicted stroke than CHADS2 and CHA2DS2-VASc scores. PMID- 26882309 TI - Simultaneous Assessment of Acidogenesis-Mitigation and Specific Bacterial Growth Inhibition by Dentifrices. AB - Dentifrices can augment oral hygiene by inactivating bacteria and at sub-lethal concentrations may affect bacterial metabolism, potentially inhibiting acidogenesis, the main cause of caries. Reported herein is the development of a rapid method to simultaneously measure group-specific bactericidal and acidogenesis-mitigation effects of dentifrices on oral bacteria. Saliva was incubated aerobically and anaerobically in Tryptone Soya Broth, Wilkins-Chalgren Broth with mucin, or artificial saliva and was exposed to dentifrices containing triclosan/copolymer (TD); sodium fluoride (FD); stannous fluoride and zinc lactate (SFD1); or stannous fluoride, zinc lactate and stannous chloride (SFD2). Minimum inhibitory concentrations (MIC) were determined turbidometrically whilst group-specific minimum bactericidal concentrations (MBC) were assessed using growth media and conditions selective for total aerobes, total anaerobes, streptococci and Gram-negative anaerobes. Minimum acid neutralization concentration (MNC) was defined as the lowest concentration of dentifrice at which acidification was inhibited. Differences between MIC and MNC were calculated and normalized with respect to MIC to derive the combined inhibitory and neutralizing capacity (CINC), a cumulative measure of acidogenesis-mitigation and growth inhibition. The overall rank order for growth inhibition potency (MIC) under aerobic and anaerobic conditions was: TD> SFD2> SFD1> FD. Acidogenesis mitigation (MNC) was ordered; TD> FD> SFD2> SFD1. CINC was ordered TD> FD> SFD2> SFD1 aerobically and TD> FD> SFD1> SFD2 anaerobically. With respect to group specific bactericidal activity, TD generally exhibited the greatest potency, particularly against total aerobes, total anaerobes and streptococci. This approach enables the rapid simultaneous evaluation of acidity mitigation, growth inhibition and specific antimicrobial activity by dentifrices. PMID- 26882310 TI - The effects of cochlear implantation in Japanese single-sided deafness patients: five case reports. AB - CONCLUSION: Cochlear implantation (CI) for Japanese single-sided deafness patients resulted in improved speech perception, increased sound localization accuracy, and reduced tinnitus handicap. OBJECTIVES: This study reports results for five adult SSD cases with CI, focusing on the benefits they obtained in terms of speech recognition, sound localization, and tinnitus handicap. METHODS: Five Japanese patients meeting the eligibility criteria were included in this study. All patients were implanted with a fully inserted MED-EL Concerto FLEX28(r) implant (MED-EL, Innsbruck, Austria). Speech perception outcomes in noise, as well as sound localization and tinnitus disturbance, were assessed pre-surgically and at 1, 3, 6, and 12 months after CI activation. RESULTS: The Japanese monosyllable test score in noise improved gradually after implantation. In some cases, speech perception ability appeared unstable, particularly in the first 1-6 months after implantation. The sound localization ability showed marked improvement in all cases, with the disturbance to daily life caused by tinnitus also decreasing in all cases from the early post-operative period. PMID- 26882311 TI - Rigid Single Carbon-Carbon Bond That Does Not Rotate in Water. AB - Carbon-carbon bond is one of the most ubiquitous molecular building blocks for natural and man-made materials. Rotational isomerization is fundamentally important for understanding the structure and reactivity of chemical and biological molecules. Reported herein is the first demonstration that a single C C bond does not rotate in water. The two distal C-S bonds in both 1,2 ethanedithiolate ((-)S-CH2-CH2-S(-), 1,2-EDT(2-)) and 2,3-butanedithiolate (2,3 BuDT(2-)) are exclusively in the trans conformer with reference to their respective center single C-C bond. In contrast, both trans and gauche conformers are observed in neutral 1,2-ethanedithiol (1,2-EDT) and 2, 3-butanedithiol (2,3 BuDT). The insight from this work should be important for understanding the charge effect on the molecular conformation in aqueous solutions. PMID- 26882312 TI - Conditional Tissue-Specific Foxa2 Ablation in Mouse Pancreas Causes Hyperinsulinemic Hypoglycemia. AB - The forkhead/winged helix transcription factor Foxa2 is a major upstream regulator of Pdx1, a transcription factor necessary for pancreatic development. In the present study, we conditionally knocked out Foxa2 in Pdx1-expressing domain and further analyzed the contribution of Foxa2 to alpha- and beta-cell development and the effect of Foxa2 deletion on plasma insulin, glucagon, and glucose levels. Homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice were generated by homologous recombination using a Foxa2 gene-targeting vector. alpha- and beta-cell mass was examined by immunofluorescence microscopy. Plasma glucose, insulin, and plasma were measured at postnatal day 10. For pdx1 lineage tracing studies, heterozygous pdx1 Foxa2 EYFP and homozygous pdx1 Foxa2 EYFP mice were used. Our immunofluorescence analysis revealed that in the pancreas sections of the homozygous mutant mice, Foxa2 was virtually absent from non-beta cells and its expression almost exclusively coincided with remnant beta cells. The density of both alpha and beta cells apparently decreased in the pancreas of the heterozygous mutant mice and in the pancreas of the homozygous mutant mice, alpha cells lost its predominance and beta cells increased proportionally. Direct Pdx1 cell lineage tracing revealed that, on embryonic day 18.5, in the homozygous mutant mice, Pdx1 expression coincided almost exclusively with that of insulin secreting beta cells. Chemiluminescence assays revealed that heterozygous pdx1 Foxa2 mice had significantly lower insulin levels than control mice (P < 0.01). However, no apparent difference was observed between homozygous pdx1 Foxa2 mice and control mice (P > 0.05). Chemiluminescence assays also showed that Foxa2 deletion significantly depressed plasma glucagon levels in both homozygous pdx1 Foxa2 mice and heterozygous pdx1 Foxa2 mice (P < 0.01 vs. controls). Plasma glucose on postnatal day 10 was significantly lower in homozygous pdx1 Foxa2 mice compared with control mice (P < 0.01). Our study demonstrates that homozygous Foxa2 ablation leads to an imbalance in beta/alpha ratio, profound hypoglucagonemia, inappropriate hyperinsulinemia, and hypoglycemia in mice. Our conditional tissue-specific Foxa2 ablation mouse model will be useful in elucidating regulation of normal and abnormal alpha- and beta-cell differentiation and pinpointing novel targets for diabetes control. PMID- 26882315 TI - Synergetic Influences of Mixed-Host Emitting Layer Structures and Hole Injection Layers on Efficiency and Lifetime of Simplified Phosphorescent Organic Light Emitting Diodes. AB - We used various nondestructive analyses to investigate various host material systems in the emitting layer (EML) of simple-structured, green phosphorescent organic light-emitting diodes (OLEDs) to clarify how the host systems affect its luminous efficiency (LE) and operational stability. An OLED that has a unipolar single-host EML with conventional poly(3,4 ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) showed high operating voltage, low LE (~26.6 cd/A, 13.7 lm/W), and short lifetime (~4.4 h @ 1000 cd/m(2)). However, the combined use of a gradient mixed-host EML and a molecularly controlled HIL that has increased surface work function (WF) remarkably decreased operating voltage and improved LE (~68.7 cd/A, 77.0 lm/W) and lifetime (~70.7 h @ 1000 cd/m(2)). Accumulated charges at the injecting interfaces and formation of a narrow recombination zone close to the interfaces are the major factors that accelerate degradation of charge injection/transport and electroluminescent properties of OLEDs, so achievement of simple-structured OLEDs with high efficiency and long lifetime requires facilitating charge injection and balanced transport into the EML and distributing charge carriers and excitons in EML. PMID- 26882313 TI - Development of a Xeno-Free Feeder-Layer System from Human Umbilical Cord Mesenchymal Stem Cells for Prolonged Expansion of Human Induced Pluripotent Stem Cells in Culture. AB - Various feeder layers have been extensively applied to support the prolonged growth of human pluripotent stem cells (hPSCs) for in vitro cultures. Among them, mouse embryonic fibroblast (MEF) and mouse fibroblast cell line (SNL) are most commonly used feeder cells for hPSCs culture. However, these feeder layers from animal usually cause immunogenic contaminations, which compromises the potential of hPSCs in clinical applications. In the present study, we tested human umbilical cord mesenchymal stem cells (hUC-MSCs) as a potent xeno-free feeder system for maintaining human induced pluripotent stem cells (hiPSCs). The hUC MSCs showed characteristics of MSCs in xeno-free culture condition. On the mitomycin-treated hUC-MSCs feeder, hiPSCs maintained the features of undifferentiated human embryonic stem cells (hESCs), such as low efficiency of spontaneous differentiation, stable expression of stemness markers, maintenance of normal karyotypes, in vitro pluripotency and in vivo ability to form teratomas, even after a prolonged culture of more than 30 passages. Our study indicates that the xeno-free culture system may be a good candidate for growth and expansion of hiPSCs as the stepping stone for stem cell research to further develop better and safer stem cells. PMID- 26882316 TI - Generalized selection to overcome innate immunity selects for host breadth in an RNA virus. AB - Virus-host coevolution has selected for generalized host defense against viruses, exemplified by interferon production/signaling and other innate immune function in eukaryotes such as humans. Although cell-surface binding primarily limits virus infection success, generalized adaptation to counteract innate immunity across disparate hosts may contribute to RNA virus emergence potential. We examined this idea using vesicular stomatitis virus (VSV) populations previously evolved on strictly immune-deficient (HeLa) cells, strictly immune competent (MDCK) cells, or on alternating deficient/competent cells. By measuring viral fitness in unselected human cancer cells of differing innate immunity, we confirmed that HeLa-adapted populations were specialized for innate immune deficient hosts, whereas MDCK-adapted populations were relatively more generalized for fitness on hosts of differing innate immune capacity and of different species origin. We also confirmed that HeLa-evolved populations maintained fitness in immune-deficient nonhuman primate cells. These results suggest that innate immunity is more prominent than host species in determining viral fitness at the host-cell level. Finally, our prediction was inexact that selection on alternating deficient/competent hosts should produce innate viral generalists. Rather, fitness differences among alternating host-evolved VSV populations indicated variable capacities to evade innate immunity. Our results suggest that the evolutionary history of innate immune selection can affect whether RNA viruses evolve greater host-breadth. PMID- 26882317 TI - Ecologically dependent and intrinsic genetic signatures of postzygotic isolation between sympatric host races of the leaf beetle Lochmaea capreae. AB - The fitness of hybrids might be compromised as a result of intrinsic isolation and/or because they fall between ecological niches due to their intermediate phenotypes ("extrinsic isolation"). Here, we present data from several crosses (parental crosses, F1, F2, and backcrosses) between the two host races of Lochmaea capreae on willow and birch to test for extrinsic isolation, intrinsic isolation, and environmentally dependent genetic incompatibilities. We employed a reciprocal transplant design in which offspring were raised on either host plant and their survival was recorded until adulthood. We also applied joint-scaling analysis to determine the genetic architecture of hybrid inviability. The relative fitness of the backcrosses switched between environments; furthermore, the additive genetic-environment interaction was detected as the strongest effect in our analysis. These results provide strong evidence that divergent natural selection has played a central role in the evolution of hybrid dysfunction between host races. Joint-scaling analysis detected significant negative epistatic effects that are most evident in the poor performance of F2-hybrids on willow, indicating signs of intrinsic isolation. We did not find any evidence that genetic incompatibilities are manifested independently of environmental conditions. Our findings suggest the outcome of natural hybridization between these host races is mainly affected by extrinsic isolation and a weak contribution of intrinsic isolation. PMID- 26882319 TI - Spontaneous Ejaculations in an Adolescent With Olanzapine Use: Case Report. AB - Olanzapine (OLZ) is a second-generation atypical antipsychotic (AAP) frequently used in acute and maintenance treatment of children and adolescents with psychotic disorders. Most commonly reported sexual problems caused by AAPs are decreases in libido or arousal, erectile dysfunctions, reduced/abnormal ejaculations, and problems in achieving or maintaining orgasm. Olanzapine is less commonly implicated for those adverse effects, which may reflect its more selective affinity to dopaminergic receptors or more transient effects on prolactin levels. Sexual dysfunction with AAPs, including OLZ, is reported predominantly in adult patients and adverse sexual effects in prepubertal/peripubertal patients with psychosis received scant attention. Studies and reports of sexual adverse effects of AAPs in this special population may benefit clinicians. Therefore, in this study, we report an adolescent male patient with psychosis who developed spontaneous ejaculations with OLZ and whose complaints remitted with change in treatment. PMID- 26882318 TI - The Efficacy Profile of Rotigotine During the Waking Hours in Patients With Advanced Parkinson's Disease: A Post Hoc Analysis. AB - OBJECTIVES: Transdermal delivery of rotigotine maintains stable plasma concentrations for 24 hours. Three phase 3 studies of rotigotine as add-on to levodopa in advanced Parkinson's disease showed a significant reduction in "off" time from baseline to end of maintenance (EoM). However, detailed analyses over the range of a day have not yet been performed. The objective was to examine the time course of the efficacy profile of rotigotine throughout the day. METHODS: Post hoc analysis of diary data from 3 double-blind, placebo-controlled studies of rotigotine in patients with advanced Parkinson's disease inadequately controlled with levodopa, with average "off" time of >=2.5 h/d (CLEOPATRA-PD [NCT00244387], 16-week maintenance; PREFER, 24-week maintenance; SP921 [NCT00522379], 12-week maintenance). Patients marked 30-minute intervals as "off," "on without troublesome dyskinesia," "on with troublesome dyskinesia," or "sleep." Diaries completed on the 3 days before EoM were analyzed. A 2-sample t test was performed for comparison of rotigotine + levodopa versus placebo + levodopa for mean percentage of time per status during four 6-hour periods: 12:00AM (midnight) to 6:00AM, 6:00AM to 12:00PM (noon), noon to 6:00PM, and 6:00PM to midnight. RESULTS: Data were available for 967 patients (placebo + levodopa, 260; rotigotine + levodopa, 707). During the 24-hour period at EoM, an advantage in mean percentage time spent "off" and "on without troublesome dyskinesia" was observed with rotigotine + levodopa versus placebo + levodopa during the three 6-hour periods from 6:00AM to midnight (P < 0.05; exploratory analysis). CONCLUSIONS: These exploratory analyses of patients with motor fluctuations suggest that the efficacy of rotigotine transdermal patch, as captured by diary data, in reducing "off" time and increasing "on time without troublesome dyskinesia" may cover the full waking day. PMID- 26882320 TI - Effects of 36.6 GHz and static magnetic field on degree of endoreduplication in Drosophila melanogaster polytene chromosomes. AB - Purpose To study the effect of microwave (MW) irradiation and consistent action of microwaves and static magnetic field (MF) on the giant chromosomes endoreduplication in Drosophila melanogaster Meig. Materials and methods Experiments were carried out on inbred wild type Canton-S strain. Exposure to microwaves (frequency - 36.64 GHz, power density - 1 W/m(2), exposure time - 30 sec) and static magnetic field (intensity - 25 mT, exposure time - 5 min) applied at the egg stage after a 2-h oviposition. Giant chromosomes were investigated in squashed preparations of the salivary glands stained by acetoorcein by the cytomorphometric method. Preparations were obtained from Drosophila larvae at the 0 h prepupae stage. Results Exposure to microwaves increased the degree of polyteny in chromosomes (DPC) by 7.5%, and the statistical power of the impact was: h(2) = 35.3%. A similar effect occurred after the sequential action of microwaves and static magnetic field: The polyteny level of chromosomes increased by 7.4%, statistical power was: h(2) = 30.6%. Conclusions Exposure to microwaves on the stage of embryogenesis has a stimulating effect on endoreduplication in Drosophila development. The effect of microwaves was not modified by the action of the static magnetic field. PMID- 26882321 TI - Marijuana Legalization in California: Rational Implementation of the Adult Use of Marijuana Act (AUMA). PMID- 26882314 TI - Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors. AB - Allosteric modulation of GPCRs has initiated a new era of basic and translational discovery, filled with therapeutic promise yet fraught with caveats. Allosteric ligands stabilize unique conformations of the GPCR that afford fundamentally new receptors, capable of novel pharmacology, unprecedented subtype selectivity, and unique signal bias. This review provides a comprehensive overview of the basics of GPCR allosteric pharmacology, medicinal chemistry, drug metabolism, and validated approaches to address each of the major challenges and caveats. Then, the review narrows focus to highlight recent advances in the discovery of allosteric ligands for metabotropic glutamate receptor subtypes 1-5 and 7 (mGlu1 5,7) highlighting key concepts ("molecular switches", signal bias, heterodimers) and practical solutions to enable the development of tool compounds and clinical candidates. The review closes with a section on late-breaking new advances with allosteric ligands for other GPCRs and emerging data for endogenous allosteric modulators. PMID- 26882323 TI - Virtual Reality in the Assessment and Treatment of Weight-Related Disorders. AB - Virtual Reality (VR) has, for the past two decades, proven to be a useful adjunctive tool for both assessment and treatment of patients with eating disorders and obesity. VR allows an individual to enter scenarios that simulate real-life situations and to encounter food cues known to trigger his/her disordered eating behavior. As well, VR enables three-dimensional figures of the patient's body to be presented, helping him/her to reach an awareness of body image distortion and then providing the opportunity to confront and correct distortions, resulting in a more realistic body image and a decrease in body image dissatisfaction. In this paper, we describe seminal studies in this research area. PMID- 26882322 TI - Virtual Worlds versus Real Body: Virtual Reality Meets Eating and Weight Disorders. PMID- 26882324 TI - A Second Chance at Health: How a 3D Virtual World Can Improve Health Self Efficacy for Weight Loss Management Among Adults. AB - Health self-efficacy, or the beliefs in one's capabilities to perform health behaviors, is a significant factor in eliciting health behavior change, such as weight loss. Research has demonstrated that virtual embodiment has the potential to alter one's psychology and physicality, particularly in health contexts; however, little is known about the impacts embodiment in a virtual world has on health self-efficacy. The present research is a randomized controlled trial (N = 90) examining the effectiveness of virtual embodiment and play in a social virtual world (Second Life [SL]) for increasing health self-efficacy (exercise and nutrition efficacy) among overweight adults. Participants were randomly assigned to a 3D social virtual world (avatar virtual interaction experimental condition), 2D social networking site (no avatar virtual interaction control condition), or no intervention (no virtual interaction control condition). The findings of this study provide initial evidence for the use of SL to improve exercise efficacy and to support weight loss. Results also suggest that individuals who have higher self-presence with their avatar reap more benefits. Finally, quantitative findings are triangulated with qualitative data to increase confidence in the results and provide richer insight into the perceived effectiveness and limitations of SL for meeting weight loss goals. Themes resulting from the qualitative analysis indicate that participation in SL can improve motivation and efficacy to try new physical activities; however, individuals who have a dislike for video games may not be benefitted by avatar based virtual interventions. Implications for research on the transformative potential of virtual embodiment and self-presence in general are discussed. PMID- 26882325 TI - Testing Augmented Reality for Cue Exposure in Obese Patients: An Exploratory Study. AB - Binge eating is one of the key behaviors in relation to the etiology and severity of obesity. Cue exposure with response prevention consists of exposing patients to binge foods while actual eating is not allowed. Augmented reality (AR) has the potential to change the way cue exposure is administered, but very few prior studies have been conducted so far. Starting from these premises, this study was aimed to (a) investigate whether AR foods elicit emotional responses comparable to those produced by the real stimuli, (b) study differences between obese and control participants in terms of emotional responses to food, and (c) compare emotional responses to different categories of foods. To reach these goals, we assess in 15 obese (age, 44.6 +/- 13 years; body mass index [BMI], 44.2 +/- 8.1) and 15 control participants (age, 43.7 +/- 12.8 years; BMI, 21.2 +/- 1.4) the emotional responses to high-calorie (savory and sweet) and low-calorie food stimuli, presented through different exposure conditions (real, photographic, and AR). The State-Trait Anxiety Inventory was used for the assessment of state anxiety, and it was administered at the beginning and after the exposure to foods, along with the Visual Analog Scale (VAS) for Hunger and Happiness. To assess the perceived pleasantness, the VAS for Palatability was administered after the exposure to food stimuli. Heart rate, skin conductance response, and facial corrugator supercilii muscle activation were recorded. Although preliminary, the results showed that (a) AR food stimuli were perceived to be as palatable as real stimuli, and they also triggered a similar arousal response; (b) obese individuals showed lower happiness after the exposure to food compared to control participants, with regard to both psychological and physiological responses; and (c) high-calorie savory (vs. low-calorie) food stimuli were perceived by all the participants to be more palatable, and they triggered a greater arousal response. PMID- 26882326 TI - Using Virtual Reality to Distract Overweight Children from Bodily Sensations During Exercise. AB - This study analyzes the potential of virtual reality (VR) to enhance attentional distraction in overweight children as they experience bodily sensations during exercise. It has been suggested that one reason why obese children stop exercising is the perception of bodily sensations. In a counterbalanced design, a total of 109 children (33 overweight, 10-15 years old) were asked to walk twice for 6 minutes on a treadmill under one of two conditions: (a) traditional condition (TC)-focusing their attention on their physical feelings and sensations or (b) distraction condition (DC)-focusing their attention on a virtual environment. Attentional focus during exercise, bad-good feeling states (pre- and postexperimental), perceived exertion (3 minutes and post), heart rate, and enjoyment were assessed. Results indicated that overweight children focused on internal information under the TC, but they significantly shifted their attention to regard the external environment in the DC. This attentional distraction effect of VR was more intense in overweight than in normal-weight children. No differences between groups were found when examining changes in feeling states and perceived exertion. VR increased enjoyment during exercise, and children preferred exercise using virtual environments. VR is useful to promote distraction and may help overweight and obese children to enjoy exercise. PMID- 26882327 TI - Eating Disorders and Obesity in Virtual Reality: A Comprehensive Research Chart. PMID- 26882331 TI - What Other Industries Can Learn From Health Care. PMID- 26882330 TI - Neucode Labels for Multiplexed, Absolute Protein Quantification. AB - We describe a new method to accomplish multiplexed, absolute protein quantification in a targeted fashion. The approach draws upon the recently developed neutron encoding (NeuCode) metabolic labeling strategy and parallel reaction monitoring (PRM). Since PRM scanning relies upon high-resolution tandem mass spectra for targeted protein quantification, incorporation of multiple NeuCode labeled peptides permits high levels of multiplexing that can be accessed from high-resolution tandem mass spectra. Here we demonstrate this approach in cultured cells by monitoring a viral infection and the corresponding viral protein production over many infection time points in a single experiment. In this context the NeuCode PRM combination affords up to 30 channels of quantitative information in a single MS experiment. PMID- 26882333 TI - Pharmacokinetics and pharmacodynamics of incobotulinumtoxinA influencing the clinical efficacy in post-stroke spasticity. AB - INTRODUCTION: Post-stroke spasticity is a disabling neurological condition and may have a significant impact on quality of life. Ability to carry out activities of daily living is often compromised and painful contractures in the affected limbs may also develop. The prevalence of spasticity may be as high as 40% within the first year after the initial stroke event. Management of this condition focuses on improving muscle tone, function and pain. IncobotulinumtoxinA is effective in treating focal spasticity. AREAS COVERED: This review will summarize outcomes from incobotulinumtoxin A phase III trials in upper limb spasticity. Pharmacodynamics and pharmacokinetics will also be discussed along with future studies and possible indications. Literature searches used for this review include; PubMed and www.clinicaltrials.gov searches. Congress abstracts and case reports are not included. EXPERT OPINION: IncobotulinumtoxinA, is a 150 kiloDalton neurotoxin without complexing proteins and is well tolerated in patients with spasticity. There is an 80% improvement reported on spasticity and disability in several phase III studies. In the future, higher doses for upper and lower limb spasticity may be considered. Antibody formation does not seem to limit the administration of higher doses. Prospective studies are evaluating the efficacy of incobotulinumtoxin in children and adolescents with cerebral palsy. Furthermore, the clinical efficacy and immunogenic status of other botulinum neurotoxin A subtypes are currently under investigation. PMID- 26882332 TI - Treatment Sequencing for Childhood ADHD: A Multiple-Randomization Study of Adaptive Medication and Behavioral Interventions. AB - Behavioral and pharmacological treatments for children with attention deficit/hyperactivity disorder (ADHD) were evaluated to address whether endpoint outcomes are better depending on which treatment is initiated first and, in case of insufficient response to initial treatment, whether increasing dose of initial treatment or adding the other treatment modality is superior. Children with ADHD (ages 5-12, N = 146, 76% male) were treated for 1 school year. Children were randomized to initiate treatment with low doses of either (a) behavioral parent training (8 group sessions) and brief teacher consultation to establish a Daily Report Card or (b) extended-release methylphenidate (equivalent to .15 mg/kg/dose bid). After 8 weeks or at later monthly intervals as necessary, insufficient responders were rerandomized to secondary interventions that either increased the dose/intensity of the initial treatment or added the other treatment modality, with adaptive adjustments monthly as needed to these secondary treatments. The group beginning with behavioral treatment displayed significantly lower rates of observed classroom rule violations (the primary outcome) at study endpoint and tended to have fewer out-of-class disciplinary events. Further, adding medication secondary to initial behavior modification resulted in better outcomes on the primary outcomes and parent/teacher ratings of oppositional behavior than adding behavior modification to initial medication. Normalization rates on teacher and parent ratings were generally high. Parents who began treatment with behavioral parent training had substantially better attendance than those assigned to receive training following medication. Beginning treatment with behavioral intervention produced better outcomes overall than beginning treatment with medication. PMID- 26882334 TI - Simulation of Daily Snapshot Rhythm Monitoring to Identify Atrial Fibrillation in Continuously Monitored Patients with Stroke Risk Factors. AB - BACKGROUND: New technologies are diffusing into medical practice swiftly. Hand held devices such as smartphones can record short-duration (e.g., 1-minute) ECGs, but their effectiveness in identifying patients with paroxysmal atrial fibrillation (AF) is unknown. METHODS: We used data from the TRENDS study, which included 370 patients (mean age 71 years, 71% men, CHADS2 score>=1 point: mean 2.3 points) who had no documentation of atrial tachycardia (AT)/AF or antiarrhythmic or anticoagulant drug use at baseline. All were subsequently newly diagnosed with AT/AF by a cardiac implantable electronic device (CIED) over one year of follow-up. Using a computer simulation approach (5,000 repetitions), we estimated the detection rate for paroxysmal AT/AF via daily snapshot ECG monitoring over various periods, with the probability of detection equal to the percent AT/AF burden on each day. RESULTS: The estimated AT/AF detection rates with snapshot monitoring periods of 14, 28, 56, 112, and 365 days were 10%, 15%, 21%, 28%, and 50% respectively. The detection rate over 365 days of monitoring was higher in those with CHADS2 scores >=2 than in those with CHADS2 scores of 1 (53% vs. 38%), and was higher in those with AT/AF burden >=0.044 hours/day compared to those with AT/AF burden <0.044 hours/day (91% vs. 14%; both P<0.05). CONCLUSIONS: Daily snapshot ECG monitoring over 365 days detects half of patients who developed AT/AF as detected by CIED, and shorter intervals of monitoring detected fewer AT/AF patients. The detection rate was associated with individual CHADS2 score and AT/AF burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT00279981. PMID- 26882335 TI - Incidence of infectious morbidity events after second-line antiretroviral therapy initiation in HIV-infected adults in Yaounde, Cameroon. AB - BACKGROUND: Since antiretroviral therapy (ART), HIV-infected individuals experience mainly non-AIDS-related conditions, among which infectious events are prominent. We aimed to estimate incidence and describe overall spectrum of infectious events, including all grade events, among HIV-1-infected adults failing first-line ART in Yaounde, Cameroon. METHODS: All patients from Cameroon enrolled in the second-line ART 2LADY trial (ANRS12169) were included in this secondary analysis. Medical files were reviewed with predefined criteria for diagnosis assessment. Incidence rates (IR) were estimated per 100 person-years (% PY). RESULTS: A total of 302 adult patients contributing 840 PY experienced 596 infectious events (IR 71% PY). Only 29 (5%) events were graded as severe. Most frequent infections were upper respiratory tract infections (15% PY), diarrhoea (9% PY) and malaria (9% PY). A total of 369 (62%) infections occurred during the first year (IR 130% PY) followed by a persistent lower incidence during the following 3 years. Higher IR were observed in patients with CD4+ T-cell count <200 cells/mm3 for all infectious events except for mycobacterial and parasitic infections. IR of viral, bacterial and parasitic infectious events were lower in case of co-trimoxazole use in patients with CD4+ T-cell count <200 cells/mm3. CONCLUSIONS: Infectious events are common and mainly occur during the first year after treatment initiation. Second-line ART initiation had a positive impact on the entire spectrum of infectious morbidity. PMID- 26882336 TI - Sharing concerns: Interpersonal worry regulation in romantic couples. AB - Two dyadic studies investigated interpersonal worry regulation in heterosexual relationships. In Study 1, we video-recorded 40 romantic couples discussing shared concerns. Male partners' worry positively predicted female partners' interpersonal calming attempts, and negatively predicted female partners' interpersonal alerting attempts (i.e., attempts to make their partners appreciate the seriousness of concerns). Video-cued recall data also indicated that changes in partner A's worry over time positively predicted partner B's motivation to reduce partner A's worry, and that this effect was stronger when B was the female partner. Study 2 was a dyadic survey of 100 couples. Individual differences in partner A's negative affect were positive predictors of partner B's interpersonal calming, and individual differences in partner A's expressive suppression were negative predictors of partner B's interpersonal calming. Further, individual differences in male partners' expressivity were significant positive predictors of female partners' interpersonal calming, and individual differences in male partners' reappraisal were significant positive predictors of female partners' interpersonal alerting. These findings suggest that interpersonal worry regulation relates to partners' expression and intrapersonal regulation of worry, but not equally for men and women. (PsycINFO Database Record PMID- 26882337 TI - Emotional arousal predicts intertemporal choice. AB - People generally prefer immediate rewards to rewards received after a delay, often even when the delayed reward is larger. This phenomenon is known as temporal discounting. It has been suggested that preferences for immediate rewards may be due to their being more concrete than delayed rewards. This concreteness may evoke an enhanced emotional response. Indeed, manipulating the representation of a future reward to make it more concrete has been shown to heighten the reward's subjective emotional intensity, making people more likely to choose it. Here the authors use an objective measure of arousal-pupil dilation to investigate if emotional arousal mediates the influence of delayed reward concreteness on choice. They recorded pupil dilation responses while participants made choices between immediate and delayed rewards. They manipulated concreteness through time interval framing: delayed rewards were presented either with the date on which they would be received (e.g., "$30, May 3"; DATE condition, more concrete) or in terms of delay to receipt (e.g., "$30, 7 days; DAYS condition, less concrete). Contrary to prior work, participants were not overall more patient in the DATE condition. However, there was individual variability in response to time framing, and this variability was predicted by differences in pupil dilation between conditions. Emotional arousal increased as the subjective value of delayed rewards increased, and predicted choice of the delayed reward on each trial. This study advances our understanding of the role of emotion in temporal discounting. (PsycINFO Database Record PMID- 26882338 TI - Timing of Renal Replacement Therapy in Acute Kidney Injury. AB - BACKGROUND: Renal replacement therapy (RRT) is commonly and increasingly utilized in critically ill patients with severe acute kidney injury (AKI). The issue of when to start RRT in a critically ill patient with AKI has long troubled clinicians. SUMMARY: Currently, there is a paucity of high-quality evidence to guide clinician decision-making on the optimal time to start RRT. This lack of evidence has translated into wide variation in treatment patterns and practices. In patients developing life-threatening complications of AKI, the decision to start RRT is largely indisputable; however, in the absence of such complications, the optimal thresholds to start RRT that translates into improved outcomes for patients are unknown. Available evidence from observational studies and clinical trials have considerable limitations for translation to clinical practice due to their retrospective, post hoc secondary design, their small sample sizes, heterogeneity in study populations and illness severity, variation in the definitions of AKI and in the timing of or thresholds for starting RRT and the risk of residual confounding and bias related to the association between the timing of RRT and outcome. KEY MESSAGES: Several large randomized trials are planned or ongoing, and the results of these trials will greatly inform best clinical practice and will help reduce unnecessary variation in the practice of RRT prescription. For now, the decision on the appropriate time to start RRT is naturally complex, integrating numerous variables, and should largely be individualized. PMID- 26882340 TI - Correction: Arsenic Trioxide Sensitizes Glioblastoma to a Myc Inhibitor. PMID- 26882339 TI - Examining Associations between Health Information Seeking Behavior and Adult Education Status in the U.S.: An Analysis of the 2012 PIAAC Data. AB - This paper presents data from the Program for the International Assessment of Adult Competencies with a focus on the interrelationships among health information seeking behavior (HISB), and health status or use of preventive health measures for U.S. adults both with and without a high school diploma. Key results of ordinal and binary logistic regression analyses indicated that, after controlling for demographic factors, (1) adults with a high school diploma use more text-based health information sources while adults without a high school diploma use more oral sources, (2) using the Internet as a source of health information is more strongly related to reporting excellent/very good health status than having a high school diploma, (3) those without a high school diploma who use the Internet report the largest increase in health status over any other health information source, and (4) for those with learning disability or vision problem, a high facility in reading English is an important predictor of whether the Internet is used as a health information source. The Internet appears to play a key role in both enhancing health status and enabling use of preventive measures for those with and without a high school diploma; although, individuals without a high school diploma who use the Internet for health information derive substantial benefit in health status. PMID- 26882341 TI - Toroidal Interaction and Propeller Chirality of Hexaarylbenzenes. Dynamic Domino Inversion Revealed by Combined Experimental and Theoretical Circular Dichroism Studies. AB - Hexaarylbenzenes (HABs) have greatly attracted much attention due to their unique propeller-shaped structure and potential application in materials science, such as liquid crystals, molecular capsules/rotors, redox materials, nonlinear optical materials, as well as molecular wires. Less attention has however been paid to their propeller chirality. By introducing small point-chiral group(s) at the periphery of HABs, propeller chirality was effectively induced, provoking strong Cotton effects in the circular dichroism (CD) spectrum. Temperature and solvent polarity manipulate the dynamics of propeller inversion in solution. As such, whizzing toroids become more substantial in polar solvents and at an elevated temperature, where radial aromatic rings (propeller blades) prefer orthogonal alignment against the central benzene ring (C6 core), maximizing toroidal interactions. PMID- 26882342 TI - 3D Reconstruction of Coronary Artery Vascular Smooth Muscle Cells. AB - AIMS: The 3D geometry of individual vascular smooth muscle cells (VSMCs), which are essential for understanding the mechanical function of blood vessels, are currently not available. This paper introduces a new 3D segmentation algorithm to determine VSMC morphology and orientation. METHODS AND RESULTS: A total of 112 VSMCs from six porcine coronary arteries were used in the analysis. A 3D semi automatic segmentation method was developed to reconstruct individual VSMCs from cell clumps as well as to extract the 3D geometry of VSMCs. A new edge blocking model was introduced to recognize cell boundary while an edge growing was developed for optimal interpolation and edge verification. The proposed methods were designed based on Region of Interest (ROI) selected by user and interactive responses of limited key edges. Enhanced cell boundary features were used to construct the cell's initial boundary for further edge growing. A unified framework of morphological parameters (dimensions and orientations) was proposed for the 3D volume data. Virtual phantom was designed to validate the tilt angle measurements, while other parameters extracted from 3D segmentations were compared with manual measurements to assess the accuracy of the algorithm. The length, width and thickness of VSMCs were 62.9+/-14.9 MUm, 4.6+/-0.6 MUm and 6.2+/-1.8 MUm (mean+/-SD). In longitudinal-circumferential plane of blood vessel, VSMCs align off the circumferential direction with two mean angles of -19.4+/-9.3 degrees and 10.9+/-4.7 degrees , while an out-of-plane angle (i.e., radial tilt angle) was found to be 8+/-7.6 degrees with median as 5.7 degrees . CONCLUSIONS: A 3D segmentation algorithm was developed to reconstruct individual VSMCs of blood vessel walls based on optical image stacks. The results were validated by a virtual phantom and manual measurement. The obtained 3D geometries can be utilized in mathematical models and leads a better understanding of vascular mechanical properties and function. PMID- 26882343 TI - A simple aptamer-functionalized gold nanorods based biosensor for the sensitive detection of MCF-7 breast cancer cells. AB - Herein, we describe a novel approach for the rapid diagnosis of human breast carcinoma MCF-7 cells with a detection limit of 100 cells mL(-1). In our strategy, the MCF-7 cells are specially recognized by mucin 1 protein (MUC-1) aptamer-functionalized gold nanorods (GNRs) through specific interactions, whose signals are simply read out by its unique localized surface plasmon resonance (LSPR) spectra. PMID- 26882345 TI - IL-17 is not essential for inflammation and chronic pelvic pain development in an experimental model of chronic prostatitis/chronic pelvic pain syndrome. AB - Pain and inflammation in the absence of infection are hallmarks in chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) patients. The etiology of CP/CPPS is unclear, and autoimmunity has been proposed as a cause. Experimental autoimmune prostatitis (EAP) models have long been used for studying CP/CPPS. Herein, we studied prostate inflammation induction and chronic pelvic pain development in EAP using IL-12p40-KO, IL-4-KO, IL-17-KO, and wild-type (C57BL/6) mice. Prostate antigen (PAg) immunization in C57BL/6 mice induced specific Th1 and Th17 immune responses and severe prostate inflammation and cell infiltration, mainly composed of CD4 T cells and macrophages. Moreover, chronic pelvic pain was evidenced by increased allodynia responses. In immunized IL-17-KO mice, the presence of a prominent PAg-specific Th1 immune response caused similar prostate inflammation and chronic pelvic pain. Furthermore, markedly high PAg-specific Th1 immune responses, exacerbated prostate inflammation, and chronic pelvic pain were detected in immunized IL-4-KO mice. Conversely, immunized IL-12p40-KO mice developed PAg-specific Th2 immune responses, characterized by high IL-4 secretion and neither infiltration nor damage in the prostate. As observed in wild-type control animals, IL12p40-KO mice did not evidence tactile allodynia responses. Our results suggest that, as in patients, chronic pelvic pain is a consequence of prostate inflammation. After PAg immunization, a Th1-associated immune response develops and induces prostate inflammation and chronic pelvic pain. The absence of Th1 or Th2 cytokines, respectively, diminishes or enhances EAP susceptibility. In addition, IL-17 showed not to be essential for pathology induction and chronic pelvic pain development. PMID- 26882344 TI - Is duloxetine's effect on painful physical symptoms in depression an indirect result of improvement of depressive symptoms? Pooled analyses of three randomized controlled trials. AB - In treating Major Depressive Disorder with associated painful physical symptoms (PPS), the effect of duloxetine on PPS has been shown to decompose into a direct effect on PPS and an indirect effect on PPS via depressive symptoms (DS) improvement. To evaluate the changes in relative contributions of the direct and indirect effects over time, we analyzed pooled data from 3 randomized double blind studies comparing duloxetine 60 mg/d with placebo in patients with major depressive disorder and PPS. Changes from baseline in Montgomery-Asberg Depression Rating Scale total and Brief Pain Inventory-Short Form average pain score were assessed over 8 weeks. Path analysis examined the (1) direct effect of treatment on PPS and/or indirect effect on PPS via DS improvement and (2) direct effect of treatment on DS and/or indirect effect on DS via PPS improvement. At week 1, the direct effect of duloxetine on PPS (75.3%) was greater than the indirect effect through DS improvement (24.7%) but became less (22.6%) than the indirect effect (77.4%) by week 8. Initially, the direct effect of duloxetine on PPS was markedly greater than its indirect effect, whereas later the indirect effect predominated. Conversely, at week 1, the direct effect of treatment on DS (46.4%) was less than the indirect effect (53.6%), and by week 8 it superseded (62.6%) the indirect effect (37.4%). Thus, duloxetine would relieve PPS directly in the initial phase and indirectly via improving DS in the later phase. PMID- 26882347 TI - Activity-dependent dephosphorylation of paxillin contributed to nociceptive plasticity in spinal cord dorsal horn. AB - The enzymatic activity of protein tyrosine kinase Src is subjected to the regulation by C-terminal Src kinase (CSK) and protein tyrosine phosphatases (PTPs). Aberrant Src activation in the spinal cord dorsal horn is pivotal for the induction and development of nociceptive behavioral sensitization. In this study, we found that paxillin, one of the well-characterized cell adhesion components involved in cell migration and survival, integrated CSK and PTPs' signaling to regulate Src-dependent nociceptive plasticity. Paxillin localized at excitatory glutamatergic synapses in the spinal dorsal horn of mice, and the phosphorylation of Tyr118 on paxillin was necessary to associate with and target CSK at synapses. After peripheral tissue injury, the enhanced neuronal activity stimulated N methyl-D-aspartate (NMDA) subtype glutamate receptors, which initiated PTPs' signaling to catalyze Tyr118 dephosphorylation. The reduced Tyr118 phosphorylation disrupted paxillin interaction with CSK, leading to the dispersal of CSK out of synapses. With the loss of CSK-mediated inhibition, Src activity was persistently increased. The active Src potentiated the synaptic transmission specifically mediated by GluN2B subunit-containing NMDA receptors. The active Src also facilitated the induction of long-term potentiation of C fiber-evoked field potentials and exaggerated painful responses. In complete Freund's adjuvant injected mice, viral expression of phosphomimicking paxillin mutant to resume CSK synaptic localization repressed Src hyperactivity. Meanwhile, this phosphomimicking paxillin mutant blunted NMDA receptor-mediated synaptic transmission and alleviated chronic inflammatory pain. These data showed that PTPs-mediated dephosphorylation of paxillin at Tyr118 was involved in the modification of nociceptive plasticity through CSK-Src signaling. PMID- 26882346 TI - A combined electrophysiological and morphological study of neuropeptide Y expressing inhibitory interneurons in the spinal dorsal horn of the mouse. AB - The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We therefore used a combined electrophysiological/morphological approach to investigate these cells in mice that express green fluorescent protein (GFP) under control of the NPY promoter. We show that GFP is largely restricted to NPY-immunoreactive cells, although it is only expressed by a third of those in lamina I-II. Reconstructions of recorded neurons revealed that they were morphologically heterogeneous, but never islet cells. Many NPY-GFP cells (including cells in lamina III) appeared to be innervated by C fibres that lack transient receptor potential vanilloid-1, and consistent with this, we found that some lamina III NPY-immunoreactive cells were activated by mechanical noxious stimuli. Projection neurons in lamina III are densely innervated by NPY containing axons. Our results suggest that this input originates from a small subset of NPY-expressing interneurons, with the projection cells representing only a minority of their output. Taken together with results of previous studies, our findings indicate that somatodendritic morphology is of limited value in classifying functional populations among inhibitory interneurons in the dorsal horn. Because many NPY-expressing cells respond to noxious stimuli, these are likely to have a role in attenuating pain and limiting its spread. PMID- 26882348 TI - Modelling Visual Change Detection and Identification under Free Viewing Conditions. AB - We examined whether the abilities of observers to perform an analogue of a real world monitoring task involving detection and identification of changes to items in a visual display could be explained better by models based on signal detection theory (SDT) or high threshold theory (HTT). Our study differed from most previous studies in that observers were allowed to inspect the initial display for 3s, simulating the long inspection times typical of natural viewing, and their eye movements were not constrained. For the majority of observers, combined change detection and identification performance was best modelled by a SDT-based process that assumed that memory resources were distributed across all eight items in our displays. Some observers required a parameter to allow for sometimes making random guesses at the identities of changes they had missed. However, the performance of a small proportion of observers was best explained by a HTT-based model that allowed for lapses of attention. PMID- 26882349 TI - Sexually Diergic Trophic Effects of Estradiol Exposure on Developing Bovine Cerebellar Granule Cells. AB - In the mammalian brain, the differentiation of neural cells and the developmental organization of the underlying circuitry are influenced by steroid hormones. The estrogen 17-beta estradiol (E2) is one of the most potent regulators of neural growth during prenatal life, synthetized locally from steroid precursors including prenatal testicular testosterone. Estradiol promotes brain differentiation counting sexually dimorphic neural circuits by binding to the estrogen receptors, ER-alpha and ER-beta. The cerebellum has been described as a site of estrogen action and a potentially sexually dimorphic area. The goal of this study was to analyze the capacity of E2 to affect the growth of male and female fetal bovine cerebellar granule. We performed primary cultures of fetal cerebellar granules, and verified the mRNA expression of the ER-alpha and ER-beta in both sexes. Moreover, the distribution of ERs in the male and female cerebellar granules of the second fetal stage was characterized by immunohistochemistry. We measured morphological parameters in presence (or absence) of estradiol administration, focusing on the variations of the dendritic branching pattern of granule neurons. By using the nonparametric combination and permutation testing approach, we proposed a sophisticated multivariate statistical analysis to demonstrate that E2 induces multifarious and dimorphic changes in the granule cells. E2 exerts trophic effects in both female and male granules and this effect is stronger in female. Male granules treated with E2 became similar to female control granule. Bos taurus species has a long gestation and a large brain that offers an interesting alternative in comparative neuroscience. PMID- 26882350 TI - Antibiotics detected in urines and adipogenesis in school children. AB - BACKGROUND: Although antibiotic use during early life has been demonstrated to be related to the altered adipogenesis in later life, limited data are available for the effect of antibiotic exposure in school children on adiposity from various sources, including from the use or contaminated food or drinking water. OBJECTIVE: To explore the association between the internal exposure of antibiotics from various sources and adipogenesis in school children using the biomonitoring of urinary antibiotics. METHODS: After 586 school children aged 8 11years were selected from Shanghai in 2013, total urinary concentrations (free and conjugated) of 21 common antibiotics from six categories (macrolides, beta lactams, tetracyclines, fluoroquinolones, sulfonamides, and phenicols), including five human antibiotics (HAs), two antibiotics preferred as HA, four veterinary antibiotics (VAs), and ten antibiotics preferred as VA, were measured by ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Creatinine-corrected urinary concentrations of antibiotics were used to assess their exposure. Overweight or obesity was determined by the body mass index or waist circumference-based criteria deriving from national data. RESULTS: All 21 antibiotics were found in urines with the overall detection frequency of 79.6%. The multinomial logistic regression analyses showed the significant associations of overweight and obesity with the exposure to VAs and antibiotics preferred as VA, but not with HAs or antibiotics preferred as HA. After adjusted for a number of obesity-relevant variables, the odds ratios (95% confidence interval) of BMI-based obesity risk of tertiles 2 and 3 of urinary concentrations relative to tertile 1 were respectively 2.54 (1.27, 5.07) and 2.92 (1.45, 5.87) for florfenicol, 0.57 (0.12, 2.63) and 3.63 (1.41, 9.32) for trimethoprim, and 3.00 (1.56, 5.76) and 1.99 (0.99, 4.01) for sum of veterinary antibiotics. Similar results were found when the outcome used WC-based obesity risk. The associations were sex related and mainly observed in boys. CONCLUSIONS: Some types of antibiotic exposure, which were mainly from food or drinking water, were associated with an increased risk of obesity in school children. Due to the cross-sectional design, more longitudinal and experimental studies are warranted to further test these findings. PMID- 26882352 TI - Applying the pre-intentional phase of the Health Action Process Approach (HAPA) Model to investigate factors associated with intention on consistent condom use with various types of female sex partners among males who inject drugs in China. AB - Both drug injection and sexual transmission are the primary drivers of the HIV epidemic in China. This study investigated the prevalence and associated factors of intention of consistent condom use during sexual intercourse with female regular partners (RP), non-regular partners (NRP) and sex workers (FSW) among male people who inject drugs (PWID)in China. A total of 529 male non institutionalized PWID aged 18-45 years with negative/unknown HIV status were recruited by multiple methods in Dazhou and Hengyang, China. The constructs of the pre-intention phase of the Health Action Process Approach (HAPA) Model, including partner-specific HIV risk perception, condom use positive outcome expectancies, condom use negative outcome expectancies, and self-efficacy of condom use, were assessed. The prevalence of behavioral intention of consistent condom use with RP, NRP, and FSW was 32.1%, 49.1%, and 63.6%, respectively. In multivariate stepwise analysis, conditional risk perception of HIV transmission via unprotected sex with RP/NRP/FSW was associated with intention of consistent condom use with these types of female sex partners (multivariate odds ratio (ORm) = 3.25-7.06). Condom use negative outcome expectancies were associated with intention of consistent condom use with RP and NRP (ORm = 0.30-0.46), while condom use self-efficacy was associated with intention of consistent condom use with RP and FSW in the next six months (ORm = 2.24-3.81). Male PWID are at high risk of HIV transmission through sexual behaviors. The pre-intention phase of the HAPA model may be applied to plan interventions to increase behavioral intention of consistent condom use with various types of female partners. Such interventions are warranted. PMID- 26882351 TI - Odontogenic Differentiation of Human Dental Pulp Stem Cells on Hydrogel Scaffolds Derived from Decellularized Bone Extracellular Matrix and Collagen Type I. AB - OBJECTIVES: The aim of this study was to evaluate the level of odontogenic differentiation of dental pulp stem cells (DPSCs) on hydrogel scaffolds derived from bone extracellular matrix (bECM) in comparison to those seeded on collagen I (Col-I), one of the main components of dental pulp ECM. METHODS: DPSCs isolated from human third molars were characterized for surface marker expression and odontogenic potential prior to seeding into bECM or Col-I hydrogel scaffolds. The cells were then seeded onto bECM and Col-I hydrogel scaffolds and cultured under basal conditions or with odontogenic and growth factor (GF) supplements. DPSCs cultivated on tissue culture polystyrene (TCPS) with and without supplements were used as controls. Gene expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1) and matrix extracellular phosphoglycoprotein (MEPE) was evaluated by quantitative reverse transcription-polymerase chain reaction (qRT PCR) and mineral deposition was observed by Von Kossa staining. RESULTS: When DPSCs were cultured on bECM hydrogels, the mRNA expression levels of DSPP, DMP-1 and MEPE genes were significantly upregulated with respect to those cultured on Col-I scaffolds or TCPS in the absence of extra odontogenic inducers. In addition, more mineral deposition was observed on bECM hydrogel scaffolds as demonstrated by Von Kossa staining. Moreover, DSPP, DMP-1 and MEPE mRNA expressions of DPSCs cultured on bECM hydrogels were further upregulated by the addition of GFs or osteo/odontogenic medium compared to Col-I treated cells in the same culture conditions. SIGNIFICANCE: These results demonstrate the potential of the bECM hydrogel scaffolds to stimulate odontogenic differentiation of DPSCs. PMID- 26882355 TI - Erratum. PMID- 26882354 TI - Biologic Drugs in Crohn's Disease and Ulcerative Colitis: Safety Profile. AB - Ulcerative Colitis (UC) and Crohn's Disease (CD) are chronic, progressive and disabling disorders characterized by a heterogeneous clinical course. Some years ago the main goal of the therapy was to achieve and maintain clinical remission, whereas at present the main goal of therapy is represented by the deep remission, characterized by sustained clinical remission, complete mucosal healing and normalization of serological markers of inflammation. In the last years new therapeutic approaches have been introduced which have led to a reduction in the mortality rate and have modified the natural history of Inflammatory Bowel Diseases (IBD). In addition, several prognostic factors have been identified which have allowed to better stratify the disease and to choose the most appropriate therapy for the single patient. Moreover, early treatment with immunosuppressive drugs and/or biologics has changed, at least in the short term, the course of the disease by reducing hospitalization rate and the need for surgery. Therefore, the development of biologic therapies has represented an important step in the treatment of IBD, since these drugs induce remission and response rates that are not achieved by other therapies. Since their use can result in significant adverse events that increase morbidity, patients must be aware of the risks associated with treatment and must be strictly monitored. Although treatment with biologic drugs is not successful in all patients and many of them lose clinical response, new therapies are currently under evaluation. PMID- 26882356 TI - Evaluation of the Innermost Retinal Layers and Visual Evoked Potentials in Patients with Multiple Sclerosis. AB - PURPOSE: The present study was conducted to investigate alterations in the innermost layers of the retina using optical coherence tomography (OCT) and to assess potential associations of structural measures with functional markers in patients with Multiple Sclerosis (MS). MATERIALS AND METHODS: Ninety-four eyes of 47 MS patients and 60 eyes of 30 healthy individuals were included in the study. All patients underwent complete ophthalmological examination and OCT imaging to analyze peripapillary retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. Visual evoked potentials (VEPs) and expanded disability status scale (EDSS) score were assessed for MS patients. RESULTS: The average RNFL and GCIPL thicknesses were thinner in MS patients (86.2 +/- 11.9 um and 73.6 +/- 9.7 um, respectively) when compared with those of healthy controls (96.7 +/- 8.2 um and 85.9 +/- 4.6 um, respectively, p < 0.001 for both). Within MS patients, the average RNFL and GCIPL thicknesses were lower in eyes with a prior history of optic neuritis (MS ON) than in eyes with no optic neuritis history (MS non-ON) (p = 0.012 and p < 0.001, respectively). RNFL and GCIPL thicknesses were inversely correlated with VEP latency (r = -0.40, p < 0.001 and r = -0.36, p < 0.001, respectively) in MS patient eyes. There was a correlation between GCIPL thickness and VEP amplitude in eyes with previous ON history (r = 0.34, p = 0.035). No significant correlations were found between OCT measurements and EDSS score. CONCLUSIONS: Innermost layers of the retina are highly affected by the pathophysiologic process in MS disease, manifesting as a reduction in RNFL and GCIPL thickness. The structural retinal changes show correlation with alterations in potentials showing the optic pathway function. PMID- 26882357 TI - Fulvestrant for the treatment of endometrial cancer. AB - INTRODUCTION: About one third of patients with endometrial cancer (EC) relapse and face a limited prognosis, if surgery or radiotherapy are not feasible. The remaining therapeutic options are chemotherapy and endocrine therapy. AREAS COVERED: This review summarizes the development of the first selective estrogen receptor (ER) down-regulator fulvestrant. This article provides its mechanism of action, pharmacokinetics and the available preclinical and clinical data. Furthermore, this review provides an overview of the market of treatments for recurrent or metastatic EC (RMEC) while also taking into account studies of fulvestrant in metastatic breast cancer. EXPERT OPINION: Even if fulvestrant showed only marginal activity in two phase II trials, it shouldn't be abandoned but instead further developed in EC. Firstly, the dose of fulvestrant used in these trials was too low from today's point of view. Secondly, the available literature on other endocrine agents is full of limitations and does not provide a gold standard. Furthermore, given the activity of mTOR inhibitors in EC, there may also be synergistic effects, given the cross-regulation of ER and the PI3K/AKT/mTOR pathway. The authors suggest that a prospective, phase II trial in ER positive RMEC would help to further explore the efficacy and tolerability of fulvestrant together with a mTOR inhibitor. PMID- 26882358 TI - Refining the Diagnosis of Congenital Nephrotic Syndrome on Long-term Stored Tissue: c.1097G>A (p.(Arg366His)) WT1 Mutation Causing Denys Drash Syndrome. AB - Congenital nephrotic syndrome (CNS) caused by a mutation in the Wilms tumor 1 suppressor gene (WT1) is part of Denys Drash Syndrome or Frasier syndrome. In the framework of genetic counseling, the diagnosis of CNS can be refined with gene mutation studies on long-term stored formalin-fixed paraffin-embedded tissue from postmortem examination. We report a case of diffuse mesangial sclerosis with perinatal death caused by a de novo mutation in the WT1 gene in a girl with an XY genotype. This is the first case of Denys Drash Syndrome with the uncommon missense c.1097G>A [p.(Arg366His)] mutation in the WT1 gene which has been diagnosed on long-term stored formalin-fixed paraffin-embedded tissue in 1993. This emphasizes the importance of retained and adequately stored tissue as a resource in the ongoing medical care and counseling. PMID- 26882359 TI - A Look to the Future: Big Data in Neurorehabilitation. PMID- 26882360 TI - The Rise of Big Data in Neurorehabilitation. AB - In some fields, Big Data has been instrumental in analyzing, predicting, and influencing human behavior. However, Big Data approaches have so far been less central in speech-language pathology. This article introduces the concept of Big Data and provides examples of Big Data initiatives pertaining to adult neurorehabilitation. It also discusses the potential theoretical and clinical contributions that Big Data can make. The article also recognizes some impediments in building and using Big Data for scientific and clinical inquiry. PMID- 26882361 TI - AphasiaBank as BigData. AB - AphasiaBank has used a standardized protocol to collect narrative, procedural, personal, and descriptive discourse from 290 persons with aphasia, as well as 190 control participants. These data have been transcribed in the Codes for the Human Analysis of Transcripts (CHAT) format for analysis by the Computerized Language Analysis (CLAN) programs. Here, we review results from 45 studies based on these data that investigate aphasic productions in terms of these eight areas: discourse, grammar, lexicon, gesture, fluency, syndrome classification, social factors, and treatment effects. For each area, we also indicate how use of the CLAN programs has facilitated the analysis. We conclude with an examination of ways in which the size of the database could be increased through on-site recordings and data from teletherapy. PMID- 26882362 TI - Verb Production in Aphasia: Testing the Division of Labor between Syntax and Semantics. AB - Some individuals with aphasia preferably use semantically general light verbs, whereas others prefer semantically specific heavy verbs. This study aimed to test Gordon and Dell's "division of labor" hypothesis that light versus heavy verb usage depends on syntactic and semantic processes, respectively. In a retrospective analysis of data from the AphasiaBank corpus, narrative language of neurologically healthy individuals and individuals with aphasia was analyzed for the proportion of light verbs used, and its relationship with narrative measures of syntactic and semantic sophistication and verb naming scores was examined. In individuals with aphasia, light verb usage was positively correlated with a syntactic measure (developmental sentence score) and negatively associated with two semantic measures (idea density and verb naming). For healthy individuals, the number of verbs per utterance, which is a measure of syntactic complexity, predicted light verb use. These findings suggest that light verb usage in aphasia observes an inverse relationship with syntactic and semantic abilities, supporting the division of labor hypothesis. PMID- 26882363 TI - Verb Argument Structure in Narrative Speech: Mining AphasiaBank. AB - Previous research has found that verb argument structure characteristics (such as the number of participant roles in the situation described by the verb) can facilitate or hinder aphasic language production and comprehension in constrained laboratory tasks. This research needs to be complemented by studies of narrative or unrestricted speech, which can capture the spontaneous selection of verbs and grammatical structures by people with aphasia and may be particularly sensitive to the relative cost of access to different verb types in more natural conditions. Focusing on the number of subcategorization options, we investigated verb argument structure effects in a large sample of narratives from AphasiaBank, by speakers with aphasia, as well as control speakers without brain damage. Verb argument structure complexity did not negatively affect verb selection in any type of aphasia. However, people with aphasia, particularly with Broca's aphasia, used verbs in less complex and diverse ways, with fewer arguments and less diverse subcategorization options. In line with previous research, this suggests that deficits in verb use in aphasia are likely due to difficulties with the online application of or partial damage to verb argument structure knowledge. PMID- 26882364 TI - How Does Severity of Aphasia Influence Individual Responsiveness to Rehabilitation? Using Big Data to Understand Theories of Aphasia Rehabilitation. AB - Our ability to make great progress in delivering, optimizing, and predicting rehabilitation outcomes for individuals with aphasia is challenged by factors that influence rehabilitation outcomes. These include patient demographic factors such as age, education, and neurologic factors such as time poststroke, the site and size of the lesion, and the resulting severity of language impairment. Also variable across individuals is the type of treatment and its duration and intensity. This article examines the utility of big data analysis for understanding one of these factors, severity of impairment, and how individual responsiveness to rehabilitation is influenced by a patient's severity of language and cognitive impairment(s). Using examples from two studies and a larger data set, we show that when rehabilitation is tailored to an individual's specific level of impairment, severe and mild patients both show improvements in accuracy and latency. Furthermore, more severe patients tend to show substantial gains on targeted rehabilitation tasks as well as on standardized tests. These results provide support for recent reviews of aphasia rehabilitation studies in concluding that systematic aphasia rehabilitation is indeed effective, and importantly, severity is not a negative prognostic indicator for successful outcomes. PMID- 26882365 TI - Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema. AB - Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy. PMID- 26882366 TI - Role of Oxidative Stress Markers in Left-Sided Valve Disease: The LDL-Density Pressure Theory. PMID- 26882367 TI - Seeking wider access to HIV testing for adolescents in sub-Saharan Africa. AB - More than 80% of the HIV-infected adolescents live in sub-Saharan Africa. Acquired immune deficiency syndrome (AIDS)-related mortality has increased among adolescents 10-19 y old. The impact is highest in sub-Saharan Africa, where >80% of HIV-infected adolescents live. The World Health Organization has cited inadequate access to HIV testing and counseling (HTC) as a contributing factor to AIDS-related adolescent deaths, most of which occur in sub-Saharan Africa. This review focuses on studies conducted in high adolescent HIV-burden countries targeted by the "All In to End Adolescent AIDS" initiative, and describes barriers to adolescent HTC uptake and coverage. Fear of stigma and family reaction, fear of the impact of a positive diagnosis, perceived risk with respect to sexual exposure, poor attitudes of healthcare providers, and parental consent requirements are identified as major impediments. Most-at-risk adolescents for HIV infection and missed opportunities for testing include, those perinatally infected, those with early sexual debut, high mobility and multiple/older partners, and pregnant and nonpregnant females. Regional analyses show relatively low adolescent testing rates and more restrictive consent requirements for HTC in West and Central Africa as compared to East and southern Africa. Actionable recommendations for widening adolescent access to HTC and therefore timely care include minimizing legal consent barriers, healthcare provider training, parental education and involvement, and expanding testing beyond healthcare facilities. PMID- 26882368 TI - DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children. AB - BACKGROUND: The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited. METHODS: We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-y-old children (n = 266). Tanner staging was completed six times between ages 9 and 12 y to determine pubertal status, and hormone levels were measured in 12-y-old boys. RESULTS: Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-y-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-y-old girls with odds of experiencing menarche by age 12 (OR (95% CI): 0.63 (0.46, 0.87); P = 0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 y with luteinizing hormone (LH), testosterone and follicle-stimulating hormone levels in boys but it was only significant between LINE-1 and LH. CONCLUSION: DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies. PMID- 26882369 TI - Histopathological features of gastrointestinal mucosal biopsies in children with juvenile idiopathic arthritis. AB - BACKGROUND: The association between inflammatory bowel disease and joint involvement is well established. There is a paucity of data describing histopathological features of the gut in relation to juvenile idiopathic arthritis (JIA). METHODS: We retrospectively identified 33 (21 male) children aged 3-16 y with JIA (11 with oligoarthritis, 5 with polyarthritis, 8 with systemic onset arthritis, 8 with enthesitis-related arthritis (ERA), and 1 with psoriatic arthritis) with significant gastrointestinal (GI) symptoms who underwent upper and/or lower endoscopy. The histopathological findings were reviewed in addition to presence of autoantibodies and concomitant treatment. RESULTS: The most common GI indications for endoscopy were persistent abdominal pain (14/33 (42%)) and diarrhea (10/33 (30%)). Of the 33 children, 28 (85%) had gut mucosal inflammation, mostly affecting the colon (80%). Active inflammation of the gut was found in 5 of 28 (17%) children, and 15 of 28 (53%) children showed mild nonspecific inflammation. Eight patients (27%) had predominantly an eosinophilic infiltrate. Twenty-six patients had previously received treatment for JIA. There was a negative association with the use of immunomodulators and the presence of eosinophil inflammation. CONCLUSION: The majority of children with JIA and GI symptoms have histological evidence of mild nonspecific inflammation, but some having active colitis and prominent eosinophil infiltrate. PMID- 26882370 TI - Higher protein intake increases cardiac function parameters in healthy children: metabolic programming by infant nutrition-secondary analysis from a clinical trial. AB - BACKGROUND: Protein intake may modulate cardiac structure and function in pathological conditions, but there is a lack of knowledge on potential effects in healthy infants. METHODS: Secondary analysis of an ongoing randomized clinical trial comparing two groups of infants receiving a higher (HP) or lower (LP) protein content formula in the first year of life, and compared with an observational group of breastfed (BF) infants. Growth and dietary intake were assessed periodically from birth to 2 y. Insulin-like growth factor 1 (IGF-1) axis parameters were analyzed at 6 mo in a blood sample. At 2 y, cardiac mass and function were assessed by echocardiography. RESULTS: HP infants (n = 50) showed a higher BMI z-score at 2 y compared with LP (n = 47) or BF (n = 44). Cardiac function parameters were increased in the HP group compared with the LP and were directly related to the protein intake during the first 6 mo of life. Moreover, there was an increase in free IGF-1 in the HP group at 6 mo. CONCLUSION: A moderate increase in protein supply during the first year of life is associated with higher cardiac function parameters at 2 y. IGF-1 axis modifications may, at least in part, underlie these effects. PMID- 26882371 TI - Cytokine responses in primary and secondary respiratory syncytial virus infections. AB - BACKGROUND: Primary respiratory syncytial virus (RSV) infections are characterized by high levels of IL-8 and an intense neutrophilia. Little is known about the cytokine responses in secondary infections. Preschool children experiencing RSV secondary infections were recruited from the siblings of infants admitted to hospital with RSV acute bronchiolitis. METHODS: Fifty-one infants with acute bronchiolitis (39 RSV positive, 12 RSV negative) and 20 age-matched control infants were recruited. In addition, seven older siblings of infants from the RSV-positive cohort and confirmed RSV infection were recruited. Samples of nasal secretions were obtained using a flocked swab, and secretions extracted using centrifugation. Cytokine bead array was used to obtain levels of interleukin (IL)-17A, IL-8, IL-6, IL-21, and tumor necrosis factor-alpha. RESULTS: Levels of IL-8 and IL-6 were significantly lower in the RSV-positive siblings compared with the RSV-positive infants. There were no significant differences between levels of the other cytokines in the primary and secondary infections. CONCLUSION: The very high levels of IL-8 and IL-6 response characteristic of the primary RSV infection was not observed in secondary RSV positive infections and this did not appear to be due to a global reduction in cytokine production. PMID- 26882372 TI - Optimal Information Representation and Criticality in an Adaptive Sensory Recurrent Neuronal Network. AB - Recurrent connections play an important role in cortical function, yet their exact contribution to the network computation remains unknown. The principles guiding the long-term evolution of these connections are poorly understood as well. Therefore, gaining insight into their computational role and into the mechanism shaping their pattern would be of great importance. To that end, we studied the learning dynamics and emergent recurrent connectivity in a sensory network model based on a first-principle information theoretic approach. As a test case, we applied this framework to a model of a hypercolumn in the visual cortex and found that the evolved connections between orientation columns have a "Mexican hat" profile, consistent with empirical data and previous modeling work. Furthermore, we found that optimal information representation is achieved when the network operates near a critical point in its dynamics. Neuronal networks working near such a phase transition are most sensitive to their inputs and are thus optimal in terms of information representation. Nevertheless, a mild change in the pattern of interactions may cause such networks to undergo a transition into a different regime of behavior in which the network activity is dominated by its internal recurrent dynamics and does not reflect the objective input. We discuss several mechanisms by which the pattern of interactions can be driven into this supercritical regime and relate them to various neurological and neuropsychiatric phenomena. PMID- 26882373 TI - A curve-free Bayesian decision-theoretic design for two-agent Phase I trials. AB - Although Bayesian statistical methods are gaining attention in the medical community, as they provide a natural framework for incorporating prior information, the complexity of these methods limited their adoptions in clinical trials. This article proposes a Bayesian design for two-agent Phase I trials that is relatively easy for clinicians to understand and implement, yet performs comparably to more complex designs, so that it is more likely to be adopted in actual trials. In order to reduce model complexity and computational burden, we choose a working model with conjugate priors so that the posterior distributions have analytical expressions. Furthermore, we provide a simple strategy to facilitate the specification of priors based on the toxicity information accrued from single-agent Phase I trials. The proposed method should be useful in terms of the ease of implementation and the savings in sample size without sacrificing performance. Moreover, the conservativeness of the dose-finding algorithm renders it a relatively safe method. PMID- 26882374 TI - [Not Available]. PMID- 26882375 TI - Current diagnosis and treatment of basal cell carcinoma. AB - Basal cell carcinoma represents is most common tumor in fair-skinned individuals. In Germany, age-standardized incidence rates are 63 (women) and 80 (men) per 100,000 population per year. Early lesions may be difficult to diagnose merely on clinical grounds. Here, noninvasive diagnostic tools such as optical coherence tomography and confocal laser scanning microscopy may be helpful. The clinical diagnosis is usually confirmed by histology. Standard therapy consists of complete excision with thorough histological examination, either by means of micrographic surgery or, depending on tumor size and location as well as infiltration, using surgical margins of 3-5 mm or more. In particular, multiple basal cell carcinomas (such as in Gorlin-Goltz syndrome) and locally advanced as well as rarely also metastatic basal cell carcinoma may pose a therapeutic challenge. In superficial basal cell carcinoma, nonsurgical therapies such as photodynamic therapy or topical agents may be considered. In case of locally advanced or metastatic basal cell carcinoma, an interdisciplinary tumor board should issue therapeutic recommendations. These include radiation therapy as well as systemic therapy with a hedgehog inhibitor. PMID- 26882378 TI - Do long-chain omega-3 fatty acids protect from atopic dermatitis? AB - Long-chain polyunsaturated fatty acids are essential for human nutrition. The number of double bonds determines whether a given fatty acid is termed two, three, or x times unsaturated. Depending on the distance of the first double bond from the fatty acid's methyl group, one distinguishes omega-3 fatty acids from omega-6 fatty acids. While the use of gamma linolenic acid, a long-chain fatty acid of the omega-6 family, has proven unsuccessful in the prevention or treatment of atopic dermatitis, supplementation of long-chain omega-3 fatty acids may represent a promising approach in the prevention of allergic disorders, especially atopic dermatitis. Whether the concept of long-chain omega-3 fatty acid administration will also become established in a therapeutic setting, depends on whether the beneficial effects observed so far can be substantiated in randomized controlled intervention studies. PMID- 26882379 TI - High-definition optical coherence tomography - an aid to clinical practice and research in dermatology. AB - At present, beyond clinical assessment, the diagnosis of skin diseases is primarily made histologically. However, skin biopsies have many disadvantages, including pain, scarring, risk of infection, and sampling error. With recent advances in skin imaging technology, the clinical use of imaging methods for the practical management of skin diseases has become an option. The in vivo high definition optical coherence tomography (HD-OCT) has recently been developed and commercialized (Skintell; Agfa, Belgium). Compared with conventional OCT, it has a higher resolution; compared with reflectance confocal microscopy, it has a shorter time for image acquisition as well as a greater penetration depth and a larger field of view. HD-OCT is promising but much work is still required to develop it from a research tool to a valuable adjunct for the noninvasive diagnosis of skin lesions. Substantial work has been done to identify HD-OCT features in various diseases but interpretation can be time-consuming and tedious. Projects aimed at automating these processes and improving image quality are currently under way. PMID- 26882381 TI - Medical error analysis in dermatology according to the reports of the North Rhine Medical Association from 2004-2013. AB - BACKGROUND: Patient safety is a central issue of health care provision. There are various approaches geared towards improving health care provision and patient safety. By conducting a systematic retrospective error analysis, the present article aims to identify the most common complaints brought forth within the field of dermatology over a period of ten years. METHODS: The reports of the Expert Committee for Medical Malpractice Claims of the North Rhine Medical Association (from 2004 to 2013) on dermatological procedures were analyzed (n = 247 reports in the field of dermatology). RESULTS: Expert medical assessments in the field of dermatology are most frequently commissioned for nonsurgical therapies (e.g. laser therapy, phototherapy). While suspected diagnostic errors constitute the second most common reason for complaints, presumed dermatosurgery related errors represent the least common reason for commissioning expert medical assessments. CONCLUSIONS: The most common and easily avoidable sources of medical errors include failure to take a biopsy despite suspicious clinical findings, or incorrect clinicopathological correlations resulting in deleterious effects for the patient. Furthermore, given the potential for incorrect indications and the inadequate selection of devices to be used as well as their parameter settings, laser and phototherapies harbor an increased risk in the treatment of dermatological patients. The fourth major source of error leading to complaints relates to incorrect indications as well as incorrect dosage and administration of drugs. Analysis of expert medical assessment reports on treatment errors in dermatology as well as other medical specialties is helpful and provides an opportunity to identify common sources of error and error-prone structures. PMID- 26882384 TI - Verrucous seborrheic keratosis with keratoacanthoma-like features, a pitfall in differential diagnosis. PMID- 26882388 TI - Non-tender pedal plaques and nodules: pseudo-Kaposi's sarcoma (Stewart-Bluefarb type) induced by trauma. PMID- 26882390 TI - Granulomatous dermatitis in a 29-year-old man from Bangladesh. PMID- 26882393 TI - S1 guideline: microscopically controlled surgery (MCS). AB - When using procedures that enable complete examination of surgical margins (3D histology), microscopically controlled surgery (MCS) represents a safe and proven method to confirm R0 resection of infiltrating tumors, especially at problematic sites, while preserving the adjacent tissue. This allows for excellent or good aesthetic results that are superior (cryosurgery, short-range irradiation) or equivalent (PDT) to nonsurgical and less safe procedures (PDT). PMID- 26882396 TI - [Not Available]. PMID- 26882398 TI - [Not Available]. PMID- 26882401 TI - Efficacy of adapalene/benzoyl peroxide combination in moderate inflammatory acne and its impact on patient adherence. PMID- 26882403 TI - HIGH D-DIMER LEVELS PREDICT A POOR OUTCOME IN PATIENTS WITH SEVERE TRAUMA, EVEN WITH HIGH FIBRINOGEN LEVELS ON ARRIVAL: A MULTICENTER RETROSPECTIVE STUDY. AB - Elevated D-dimer level in trauma patients is associated with tissue damage severity and is an indicator of hyperfibrinolysis during the early phase of trauma. To investigate the interacting effects of fibrinogen and D-dimer levels on arrival at the emergency department for massive transfusion and mortality in severe trauma patients in a multicenter retrospective study. This study included 519 adult trauma patients with an injury severity score >=16. Patients with >=10 units of red cell concentrate transfusion and/or death during the first 24 h were classified as having a poor outcome. Receiver operating characteristic curve analysis for predicting poor outcome showed the optimal cut-off fibrinogen and D dimer values to be 190 mg/dL and 38 mg/L, respectively. On the basis of these values, patients were divided into four groups: low D-dimer (<38 mg/L)/high fibrinogen (>190 mg/dL), low D-dimer (<38 mg/L)/low fibrinogen (<=190 mg/dL), high D-dimer (>=38 mg/L)/high fibrinogen (>190 mg/dL), and high D-dimer (>=38 mg/L)/low fibrinogen (<=190 mg/dL). The survival rate was lower in the high D dimer/low fibrinogen group than in the other groups. Moreover, the survival rate was lower in the high D-dimer/high fibrinogen group than in the low D-dimer/high fibrinogen and low D-dimer/low fibrinogen groups. High D-dimer level on arrival is a strong predictor of early death or requirement for massive transfusion in severe trauma patients, even with high fibrinogen levels. PMID- 26882406 TI - Insights into the Societal Risk of Nuclear Power Plant Accidents. AB - The elements of societal risk from a nuclear power plant accident are clearly illustrated by the Fukushima accident: land contamination, long-term relocation of large numbers of people, loss of productive farm area, loss of industrial production, and significant loss of electric capacity. NUREG-1150 and other studies have provided compelling evidence that the individual health risk of nuclear power plant accidents is effectively negligible relative to other comparable risks, even for people living in close proximity to a plant. The objective of this study is to compare the societal risk of nuclear power plant accidents to that of other events to which the public is exposed. We have characterized the monetized societal risk in the United States from major societally disruptive events, such as hurricanes, in the form of a complementary cumulative distribution function. These risks are compared with nuclear power plant risks, based on NUREG-1150 analyses and new MACCS code calculations to account for differences in source terms determined in the more recent SOARCA study. A candidate quantitative societal objective is discussed for potential adoption by the NRC. The results are also interpreted with regard to the acceptability of nuclear power as a major source of future energy supply. PMID- 26882402 TI - Airway Mucin 2 Is Decreased in Patients with Severe Chronic Obstructive Pulmonary Disease with Bacterial Colonization. AB - RATIONALE: Mucins are essential for airway defense against bacteria. We hypothesized that abnormal secreted airway mucin levels would be associated with bacterial colonization in patients with severe chronic obstructive pulmonary disease (COPD) Objectives: To investigate the relationship between mucin levels and the presence of potentially pathogenic micro-organisms in the airways of stable patients with severe COPD Methods: Clinically stable patients with severe COPD were examined prospectively. All patients underwent a computerized tomography scan, lung function tests, induced sputum collection, and bronchoscopy with bronchoalveolar lavage (BAL) and protected specimen brush. Patients with bronchiectasis were excluded. Secreted mucins (MUC2, MUC5AC, and MUC5B) and inflammatory markers were assessed in BAL and sputum by ELISA. MEASUREMENTS AND MAIN RESULTS: We enrolled 45 patients, with mean age (+/-SD) of 67 (+/-8) years and mean FEV1 of 41 (+/-10) % predicted. A total of 31% (n = 14) of patients had potentially pathogenic micro-organisms in quantitative bacterial cultures of samples obtained by protected specimen brush. Patients with COPD with positive cultures had lower levels of MUC2 both in BAL (P = 0.02) and in sputum (P = 0.01). No differences in MUC5B or MUC5AC levels were observed among the groups. Lower MUC2 levels were correlated with lower FEV1 (r = 0.32, P = 0.04) and higher sputum IL-6 (r = -0.40, P = 0.01). CONCLUSIONS: Airway MUC2 levels are decreased in patients with severe COPD colonized by potentially pathogenic micro-organisms. These findings may indicate one of the mechanisms underlying airway colonization in patients with severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01976117). PMID- 26882407 TI - Enantioselective Total Synthesis of (-)-Alstoscholarisine A. AB - We report a concise and highly enantioselective total synthesis of (-) alstoscholarisine A (1), a recently isolated monoterpenoid indole alkaloid that has significant bioactivity in promoting adult neuronal stem cells proliferation. A highly enantioselective (99% ee), intramolecular Ir-catalyzed Friedel-Crafts alkylation of indole 9 with a secondary allylic alcohol was utilized to establish the first stereogenic center upon which the other three contiguous chiral centers were readily set by a highly stereoselective tandem 1,4-addition and aldol reaction. The key tetrahydropyran was constructed through a hemiacetal reduction, and the final aminal bridge was forged by a one-pot reductive amination/cyclization. The conciseness of this approach was highlighted by building core bonds in each step with a minimalist protecting group strategy. PMID- 26882408 TI - To Risk Adjust or Not to Risk Adjust: Should That Be the Question? PMID- 26882409 TI - Foreword. PMID- 26882410 TI - Community Coping Strategies in Response to Hardship and Human Rights Abuses Among Burmese Refugees and Migrants at the Thai-Burmese Border: A Qualitative Approach. AB - We conducted 10 focus groups (n = 49) with community members and key informant interviews (n = 28) to explore hardships and community coping strategies for sequelae of abuse among Burmese refugees/migrants in Thailand. Transcripts were coded and analyzed for major themes. In Burma, they universally experienced human rights violations and economic hardship. Hardships continued in Thailand through exploitation and threat of deportation. Coping was achieved through both personal and community-based mechanisms including self-reflection, sharing experiences, spirituality, and serving their community. Western psychosocial counseling, although available, was used infrequently. Effective psychosocial support often originates from the community and should be supported by international organizations. PMID- 26882411 TI - A 3-Component Approach Incorporating Focus Groups in Strategic Planning for Sexual Violence Prevention. AB - Sexual violence is of special concern in New Mexico because of the presence of large priority populations in which its prevalence is high. This article describes a 3-component approach to developing a strategic plan to prevent sexual violence in the state that consisted of an advisory group, subject matter experts, and focus groups from geographically and demographically diverse communities. Both common and community-specific themes emerged from the focus groups and were included in the strategic plan. By incorporating community needs and experiences, this approach fosters increased investment in plan implementation. PMID- 26882412 TI - Sexual Violence Among Youth in New Mexico: Risk and Resiliency Factors That Impact Behavioral Health Outcomes. AB - Research has consistently demonstrated a relationship between history of forced sex and poor behavioral health outcomes. The objectives of this study were to describe this relationship among high school students and to explore the impact of resiliency factors. Using data from the 2013 New Mexico Youth Risk and Resiliency Survey, we found that history of forced sex was associated with negative behavioral health outcomes for males and females, regardless of sexual orientation and disability status. Furthermore, the presence of a caring adult at home appeared to reduce the risk of substance abuse and suicidality among students with and without a history of forced sex. PMID- 26882413 TI - Individual- and Neighborhood-Level Determinants of Fear of Violent Crime Among Adolescents. AB - Fear of violent crime is common among adolescents in urban settings; however, little is known about individual- and neighborhood-level determinants of fear. A generalized ordered logit model was used to analyze individual- and neighborhood level variables among 2474 adolescents. Seeing violence significantly reduced the probability of feeling unafraid, as did higher levels of social disorder. The more block faces where police were visible, the higher the probability of feeling unafraid and lower the probability of feeling very afraid. Reducing fear could affect more people than just reducing crime. Fear-reduction strategies should target those most at risk of becoming fearful. PMID- 26882414 TI - Gender Differences in Posttraumatic Stress Symptoms Among Participants of a Violence Intervention Program at a Pediatric Hospital: A Pilot Study. AB - Hospital-based violence intervention programs (HVIPs) have emerged as a strategy to address posttraumatic stress (PTS) symptoms among violently injured patients and their families. HVIP research, however, has focused on males and little guidance exists about how HVIPs could be tailored to meet gender-specific needs. We analyzed pediatric HVIP data to assess gender differences in prevalence and type of PTS symptoms. Girls reported more PTS symptoms than boys (6.96 vs 5.21, P = .027), particularly hyperarousal symptoms (4.00 vs 2.82, P = .002) such as feeling upset by reminders of the event (88.9% vs 48.3%, P = .005). Gender focused research represents a priority area for HVIPs. PMID- 26882415 TI - Grandparents Raising Grandchildren: A Synthetic Review and Theoretical Model for Interventions. AB - The number of custodial grandparents has increased significantly over the past decade. Building on Hayslip's and Kaminski's comprehensive review of the literature on custodial grandparenting, we conducted an updated review of the literature, in particular peer-reviewed journal articles published since 2004. We have developed a conceptual model to contribute to understanding the causes and consequences of custodial grandparenting, using the stress-coping framework while highlighting the emerging issues related to contemporary grandfamilies such as cultural and ethnic heterogeneity in grandfamilies. We also emphasized loss, grief, and trauma among grandfamilies and provided the implications for effective public and community health programs. PMID- 26882416 TI - Intimate Partner Violence and Traumatic Brain Injury: State of the Science and Next Steps. AB - Women who receive traumatic brain injuries (TBI) from intimate partner violence (IPV) are gaining attention; however, research studies are lacking in this area. A review of literature conducted on TBI from IPV found prevalence of 60% to 92% of abused women obtaining a TBI directly correlated with IPV. Adverse overlapping health outcomes are associated with both TBI and IPV. Genetic predisposition and epigenetic changes can occur after TBI and add increased vulnerability to receiving and inflicting a TBI. Health care providers and community health workers need awareness of the link between IPV/TBI to provide appropriate treatment and improve the health of women and families. PMID- 26882417 TI - Cascade DNA logic device programmed ratiometric DNA analysis and logic devices based on a fluorescent dual-signal probe of a G-quadruplex DNAzyme. AB - Herein, two fluorescence sensitive substrates of G-quadruplex/hemin DNAzyme with inverse responses (Scopoletin and Amplex Red) were simultaneously used in one homogeneous system to construct a cascade advanced DNA logic device for the first time (a functional logic device (a three input based DNA calliper) cascade with an advanced non-arithmetic logic gate (1 to 2 decoder)). This cascade logic device was applied to label-free ratiometric target DNA detection and length measurement. PMID- 26882418 TI - Editorial: Decreasing Crystal-Induced Consternation: New Methods of Crystal Identification. PMID- 26882419 TI - Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys. AB - The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. noncontingent priming injections of methamphetamine (0.03, 0.1, or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleeplike parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleeplike measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. PMID- 26882420 TI - Best Practices for Developing Specialty Nursing Scope and Standards of Practice. AB - Nursing specialization involves focusing on nursing practice in an identified specific area within the entire field of professional nursing. A defined specialty scope of practice statement and standards of professional practice, with accompanying competencies, are unique to each nursing specialty. These documents help assure continued understanding and recognition of nursing's diverse professional contributions. The purpose of this article is to demystify the process for specialty nurses who are creating or revising their specialty nursing scope and standards of practice. We provide best practices for the developmental process based on our recently published scope and standards of specialty nursing practice. The conclusion provides strategies to disseminate scope and standards documents to appropriate stakeholders. PMID- 26882421 TI - Historical Perspectives on an Expanded Role for Nursing. AB - The 2010 Institute of Medicine report, the Future of Nursing, recommended that nurses work to the "full extent of their training" to address the primary healthcare needs of United States citizens. This article identifies and describes historical antecedents, cornerstone documents, and legislative acts that served to set the stage for today, laying the groundwork for an expanded role for advanced practice nurses in the 21st century. Beginning with Lillian Wald's work in Henry Street Settlement in 1893, through Mary Breckenridge's founding of the Frontier Nursing Service in 1925, the discussion describes how nurses provided access to care for thousands of urban and rural citizens throughout the United States in the past. The article also discusses political forces at midcentury and the creation of the nurse practitioner role with the premise that nurses can learn from these early initiatives to create new models for nurses' roles in primary care today. PMID- 26882422 TI - Cornerstone Documents, Milestones, and Policies: Shaping the Direction of Public Health Nursing 1890-1950. AB - The interplay of policy, milestone events, and cornerstone documents was critical in the evolution of the specialty of public health nursing (PHN) from 1890-1950. Using our contemporary lens, this article examines PHN development from an historical perspective, including events and milestones driving growth in the early 20th century. Some of the challenges faced by our founding public health nursing leadership are not unlike challenges we face today. In 1950, Ruth Hubbard, a former leader in the National Organization of Public Health Nurses and Director of the Visiting Nurse Society of Philadelphia, spoke of the value of examining the past to forge a new future. This article calls for contemporary public health nurses to act upon the lessons learned from the past, to strengthen the renewed focus on prevention, to develop policies that impact population health, and to foster a vision that will guide us into the future. PMID- 26882423 TI - The Nursing Code of Ethics: Its Value, Its History. AB - To practice competently and with integrity, today's nurses must have in place several key elements that guide the profession, such as an accreditation process for education, a rigorous system for licensure and certification, and a relevant code of ethics. The American Nurses Association has guided and supported nursing practice through creation and implementation of a nationally accepted Code of Ethics for Nurses with Interpretive Statements. This article will discuss ethics in society, professions, and nursing and illustrate how a professional code of ethics can guide nursing practice in a variety of settings. We also offer a brief history of the Code of Ethics, discuss the modern Code of Ethics, and describe the importance of periodic revision, including the inclusive and thorough process used to develop the 2015 Code and a summary of recent changes. Finally, the article provides implications for practicing nurses to assure that this document is a dynamic, useful resource in a variety of healthcare settings. PMID- 26882424 TI - Development and Implementation of Cornerstone Documents to Support Nursing Practice in Cambodia. AB - Cornerstone, or guiding documents, for nursing and healthcare support the profession of nursing throughout the world. This article describes the impact of the civil war and instability in Cambodia that led to poverty and destruction of the healthcare system and provides a brief overview of nursing in Cambodia today. Since the 1990s, the Cambodian healthcare system has been recovering from war. Nurses have been transitioning from task oriented roles to more sophisticated roles that incorporate the nursing process. In addition to significant changes in nursing education and other advances in the healthcare system during the last five years, the Ministry of Health (MoH) has strongly encouraged the development of cornerstone documents to guide nursing practice for patient care provided in Cambodia. Standards and competencies have been developed based on the American Nurses Association (ANA) template for Scope and Standards of Practice. Cornerstone documents for nursing that have been implemented by the MoH, many at the Angkor Hospital for Children, include evidence based protocols, the nursing process framework, the Code of Ethics for Nurses and development of the Scope of Practice and Standards of Care for Cambodian Nurses. PMID- 26882425 TI - Health Information Technology, Patient Safety, and Professional Nursing Care Documentation in Acute Care Settings. AB - The electronic health record (EHR) is a documentation tool that yields data useful in enhancing patient safety, evaluating care quality, maximizing efficiency, and measuring staffing needs. Although nurses applaud the EHR, they also indicate dissatisfaction with its design and cumbersome electronic processes. This article describes the views of nurses shared by members of the Nursing Practice Committee of the Missouri Nurses Association; it encourages nurses to share their EHR concerns with Information Technology (IT) staff and vendors and to take their place at the table when nursing-related IT decisions are made. In this article, we describe the experiential-reflective reasoning and action model used to understand staff nurses' perspectives, share committee reflections and recommendations for improving both documentation and documentation technology, and conclude by encouraging nurses to develop their documentation and informatics skills. Nursing issues include medication safety, documentation and standards of practice, and EHR efficiency. IT concerns include interoperability, vendors, innovation, nursing voice, education, and collaboration. PMID- 26882426 TI - Changing the Culture of Long-Term Care: Combating Heterosexism. AB - The purpose of this article is to describe how heterosexism impedes the provision of culturally competent care for lesbian, gay, bisexual, transgender, and queer (LGBTQ) residents in long-term care (LTC) facilities. LTC facilities continue to employ staff members who lack an understanding of sexuality and sexual diversity in the elderly. In this article, we identify the heterosexual assumption, namely heterosexism, as the primary issue surrounding the holistic care of the LGBTQ elder in LTC. We first review the literature related to LGBTQ elders in LTC facilities, identifying the themes that emerged from the review, specifically the definitions of homophobia and heterosexism; perceptions of LGBTQ elders as they consider placement in LTC facilities; and staff knowledge of and biases toward sexuality and sexual diversity in LTC settings. Then, we suggest approaches for changing the culture of LTC to one in which LGBTQ elders feel safe and valued, and conclude by considering how facility leaders are in a unique position to enable LGBTQ elders to flourish in what may be their last home. PMID- 26882427 TI - Shared Governance: The Role of Buy-in in Bringing About Change. AB - The term buy-in can be found in almost any article considering individuals' participation in an initiative. At the time of this writing, a Google search of buy-in resulted in 10.5 billion hits. The term buy-in seems intuitive, yet many healthcare organizations struggle to implement and sustain initiatives that depend on nursing buy-in and involvement. The purpose of this article is to identify prerequisites to buy-in and factors that facilitate buy-in which, when cultivated, may positively influence nurse engagement. In this article, the authors discuss the concept of buy-in, identify prerequisites for buy-in, consider factors to enhance buy-in, and present scenarios of what happens when buy-in happens, when it almost happens, and when it fails. They also consider future directions to facilitate buy-in by nursing staff members. PMID- 26882428 TI - Strengthening Moral Courage Among Nurse Leaders. AB - Moral distress among practicing nurses is frequently discussed in the nursing literature, along with well-developed recommendations for increasing moral courage in practicing nurses. Implementing these recommendations depends on nurse leaders being morally fit to lead and to create an environment in which moral courage actions can emerge. The literature is lacking pertaining to nurse leaders' preparation to lead in a morally courageous and transformational manner in our current corporate environments and hierarchies of healthcare. In this article, the author reviews the literature addressing moral distress and moral courage among direct care nurses; describes the development of an intervention to strengthen the moral courage of nurse leaders; reports a study that involved implementing this intervention; presents the findings of this study; evaluates the effectiveness of the intervention; and discusses the findings in terms of lessons learned and future directions. He concludes with a call for healthcare leaders to demonstrate moral courage and create environments that promote morally courageous acts that enable nurses to remain centered on the patients, families, and communities we serve. PMID- 26882430 TI - Cochrane Review Brief: Chinese Herbal Medicines for Treating Osteoporosis. PMID- 26882429 TI - Informatics: Ethical Use of Genomic Information and Electronic Medical Records. PMID- 26882431 TI - Cochrane Review Brief: Interprofessional Education: Effects On Professional Practice and Healthcare Outcomes. PMID- 26882432 TI - Cochrane Review Brief: Discharge Planning from Hospital to Home. PMID- 26882433 TI - Ethics: Harm in the Emergency Department -- Ethical Drivers for Change. PMID- 26882435 TI - Interaction Analysis of a Two-Component System Using Nanodiscs. AB - Two-component systems are the major means by which bacteria couple adaptation to environmental changes. All utilize a phosphorylation cascade from a histidine kinase to a response regulator, and some also employ an accessory protein. The system-wide signaling fidelity of two-component systems is based on preferential binding between the signaling proteins. However, information on the interaction kinetics between membrane embedded histidine kinase and its partner proteins is lacking. Here, we report the first analysis of the interactions between the full length membrane-bound histidine kinase CpxA, which was reconstituted in nanodiscs, and its cognate response regulator CpxR and accessory protein CpxP. Using surface plasmon resonance spectroscopy in combination with interaction map analysis, the affinity of membrane-embedded CpxA for CpxR was quantified, and found to increase by tenfold in the presence of ATP, suggesting that a considerable portion of phosphorylated CpxR might be stably associated with CpxA in vivo. Using microscale thermophoresis, the affinity between CpxA in nanodiscs and CpxP was determined to be substantially lower than that between CpxA and CpxR. Taken together, the quantitative interaction data extend our understanding of the signal transduction mechanism used by two-component systems. PMID- 26882437 TI - Native State Mass Spectrometry, Surface Plasmon Resonance, and X-ray Crystallography Correlate Strongly as a Fragment Screening Combination. AB - Fragment-based drug discovery (FBDD) is contingent on the development of analytical methods to identify weak protein-fragment noncovalent interactions. Herein we have combined an underutilized fragment screening method, native state mass spectrometry, together with two proven and popular fragment screening methods, surface plasmon resonance and X-ray crystallography, in a fragment screening campaign against human carbonic anhydrase II (CA II). In an initial fragment screen against a 720-member fragment library (the "CSIRO Fragment Library") seven CA II binding fragments, including a selection of nonclassical CA II binding chemotypes, were identified. A further 70 compounds that comprised the initial hit chemotypes were subsequently sourced from the full CSIRO compound collection and screened. The fragment results were extremely well correlated across the three methods. Our findings demonstrate that there is a tremendous opportunity to apply native state mass spectrometry as a complementary fragment screening method to accelerate drug discovery. PMID- 26882436 TI - FNA smears as a potential source of DNA for targeted next-generation sequencing of lung adenocarcinomas. AB - BACKGROUND: Diff-Quik-stained fine-needle aspiration (FNA) smears and touch preparations from biopsies represent alternative specimens for molecular testing when cell block or biopsy material is insufficient. This study describes the use of these samples for targeted next-generation sequencing (NGS) of primary and metastatic lung adenocarcinoma and reports the DNA quality and success rates of FNA smears versus other specimens from 1 year of clinical use. METHODS: A validation set of 10 slides from 9 patients with prior clinical epidermal growth factor receptor (EGFR) Sanger sequencing and KRAS pyrosequencing (5 KRAS positive/EGFR-negative and 4 KRAS-negative/EGFR-negative) underwent DNA extraction, quality assessment, and targeted NGS. Subsequently, lung adenocarcinoma specimens submitted for NGS solid tumor mutation panel testing in 1 calendar year (60 biopsies, 57 resections, 33 FNA cell blocks, 12 FNA smears, and 10 body fluid cell blocks) were reviewed for specimen adequacy, sequencing success, and DNA quality. RESULTS: All 10 validation samples met the DNA quality threshold (delta Ct threshold < 8; range, -2.2 to 4.9) and yielded 0.5 to 22 MUg of DNA. The KRAS and EGFR mutation status from FNA smears according to NGS was concordant with previous clinical testing for all 10 samples. In the 1-year review, FNA smears were 100% successful, and this suggested a performance equivalent to or better than the performance of established specimen types, including FNA cell blocks. DNA quality according to DeltaCt was significantly better with FNA smears versus biopsies, resections, and FNA cell blocks. CONCLUSIONS: FNA smears of lung adenocarcinomas are high-quality alternative specimens for a targeted NGS panel with a high success rate in clinical practice. Cancer Cytopathol 2016;124:406-14. (c) 2016 American Cancer Society. PMID- 26882438 TI - High Loading of Pd Nanoparticles by Interior Functionalization of MOFs for Heterogeneous Catalysis. AB - In this report, the issue related to nanoparticle (NP) agglomeration upon increasing their loading amount into metal-organic frameworks (MOFs) has been addressed by functionalization of MOFs with alkyne groups. The alkynophilicity of the Pd(2+) (or other noble metals) ions has been utilized successfully for significant loading of Pd NPs into alkyne functionalized MOFs. It has been shown here that the size and loading amount of Pd NPs are highly dependent on the surface area and pore width of the MOFs. The loading amount of Pd NPs was increased monotonically without altering their size distribution on a particular MOF. Importantly, the distinct role of alkyne groups for Pd(2+) stabilization has also been demonstrated by performing a control experiment considering a MOF without an alkyne moiety. The preparation of NPs involved two distinct steps viz. adsorption of metal ions inside MOFs and reduction of metal ions. Both of these steps were monitored by microscopic techniques. This report also demonstrates the applicability of Pd@MOF NPs as extremely efficient heterogeneous catalysts for Heck-coupling and hydrogenation reactions of aryl bromides or iodides and alkenes, respectively. PMID- 26882439 TI - The Prevention of Epilepsy. PMID- 26882440 TI - CD44 variant 9 is a potential biomarker of tumor initiating cells predicting survival outcome in hepatitis C virus-positive patients with resected hepatocellular carcinoma. AB - This study investigated whether the expression of CD44 variant 9 (CD44v9) might be a functional marker of tumor-initiating stem-like cells in primary hepatocellular carcinomas (HCCs) of hepatitis C virus (HCV)(+) patients and provide an indicator of patient survival, as well as associated mechanisms. A total of 90 HCV(+) HCC patients who underwent surgery from 2006 to 2011 were enrolled and monitored for 2-8 years. Expression of CD44v9 was validated immunohistochemically in all HCCs, followed by comparative proteome, survival, and clinicopathological analyses. CD44 variant 8--10 was further evaluated in diethylnitrosamine-induced HCCs of C57Bl/6J mice. Focally localized CD44v(+) cells with a membranous staining pattern were detected in human HCV(+) and mouse HCCs. CD44v9(+) cells of HCCs were predominantly negative for Ki67 and P-p38, indicating decrease of cell proliferation in the CD44v9(+) tumor cell population, likely to be related to suppression of intracellular oxidative stress due to activation of Nrf2-mediated signaling, DNA repair, and inhibition of xenobiotic metabolism. CD44v9 IHC evaluation in 90 HCV(+) HCC cases revealed that positive expression was significantly associated with poor overall and recurrence-free survival, a younger age, poor histological differentiation of HCCs, and high alkaline phosphatase levels compared with patients with negative expression. CD44v9 is concluded to be a potential biomarker of tumor-initiating stem-like cells and a prognostic marker in HCV(+) HCC patients associated with Nrf2 mediated resistance to oxidative stress. PMID- 26882441 TI - Single-Nanowire Electrochemical Probe Detection for Internally Optimized Mechanism of Porous Graphene in Electrochemical Devices. AB - Graphene has been widely used to enhance the performance of energy storage devices due to its high conductivity, large surface area, and excellent mechanical flexibility. However, it is still unclear how graphene influences the electrochemical performance and reaction mechanisms of electrode materials. The single-nanowire electrochemical probe is an effective tool to explore the intrinsic mechanisms of the electrochemical reactions in situ. Here, pure MnO2 nanowires, reduced graphene oxide/MnO2 wire-in-scroll nanowires, and porous graphene oxide/MnO2 wire-in-scroll nanowires are employed to investigate the capacitance, ion diffusion coefficient, and charge storage mechanisms in single nanowire electrochemical devices. The porous graphene oxide/MnO2 wire-in-scroll nanowire delivers an areal capacitance of 104 nF/MUm(2), which is 4.0 and 2.8 times as high as those of reduced graphene oxide/MnO2 wire-in-scroll nanowire and MnO2 nanowire, respectively, at a scan rate of 20 mV/s. It is demonstrated that the reduced graphene oxide wrapping around the MnO2 nanowire greatly increases the electronic conductivity of the active materials, but decreases the ion diffusion coefficient because of the shielding effect of graphene. By creating pores in the graphene, the ion diffusion coefficient is recovered without degradation of the electron transport rate, which significantly improves the capacitance. Such single-nanowire electrochemical probes, which can detect electrochemical processes and behavior in situ, can also be fabricated with other active materials for energy storage and other applications in related fields. PMID- 26882442 TI - Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis. AB - Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control-based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction-involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride (CCl4) dissolved in olive oil (0.5 mL/kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor beta1 and alpha smooth muscle actin in response to CCl4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CCl4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN-induced putative kinase 1 (PINK1); Parkin; peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha); nuclear respiratory factor 1 (NRF1); and transcription factor A, mitochondrial (TFAM). CCl4-mediated decreases in mitochondrial fission- and fusion-related proteins, such as dynamin-related protein 1 (DRP1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP-activated protein kinase (AMPK) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment. PMID- 26882444 TI - Displaying fairness while delivering bad news: Testing the effectiveness of organizational bad news training in the layoff context. AB - Although giving bad news at work is a stressful experience, managers are often underprepared for this challenging task. As a solution, we introduce organizational bad news training that integrates (a) principles of delivering bad news from the context of health care (i.e., bad news delivery component), and (b) principles of organizational justice theory (i.e., fairness component). We argue that both the formal and fair delivery of bad news at work can be enhanced with the help of training to mitigate distress both for the messenger and the recipient. We tested the effectiveness of training for the delivery of a layoff as a typical bad news event at work. In 2 studies, we compared the performance of a training group (receiving both components of training) with that of a control group (Study 1, Study 2) and a basics group (receiving the bad news delivery component only; Study 2) during a simulated dismissal notification meeting. In general, the results supported our hypotheses: Training improved the formal delivery of bad news and predicted indicators of procedural fairness during the conversation in both studies. In Study 2, we also considered layoff victims' negativity after the layoff and found that training significantly reduced negative responses. This relationship was fully mediated by layoff victims' fairness perceptions. Despite preparation, however, giving bad news remained a challenging task in both studies. In summary, we recommend that organizations provide managers with organizational bad news training in order to promote professional and fair bad news conversations at work. (PsycINFO Database Record PMID- 26882443 TI - To branch out or stay focused? Affective shifts differentially predict organizational citizenship behavior and task performance. AB - We draw from personality systems interaction (PSI) theory (Kuhl, 2000) and regulatory focus theory (Higgins, 1997) to examine how dynamic positive and negative affective processes interact to predict both task and contextual performance. Using a twice-daily diary design over the course of a 3-week period, results from multilevel regression analysis revealed that distinct patterns of change in positive and negative affect optimally predicted contextual and task performance among a sample of 71 employees at a medium-sized technology company. Specifically, within persons, increases (upshifts) in positive affect over the course of a workday better predicted the subsequent day's organizational citizenship behavior (OCB) when such increases were coupled with decreases (downshifts) in negative affect. The optimal pattern of change in positive and negative affect differed, however, in predicting task performance. That is, upshifts in positive affect over the course of the workday better predicted the subsequent day's task performance when such upshifts were accompanied by upshifts in negative affect. The contribution of our findings to PSI theory and the broader affective and motivation regulation literatures, along with practical implications, are discussed. (PsycINFO Database Record PMID- 26882445 TI - When are do-gooders treated badly? Legitimate power, role expectations, and reactions to moral objection in organizations. AB - Organization members who engage in "moral objection" by taking a principled stand against ethically questionable activities help to prevent such activities from persisting. Unfortunately, research suggests that they also may be perceived as less warm (i.e., pleasant, nice) than members who comply with ethically questionable procedures. In this article, we draw on role theory to explore how legitimate power influences observers' responses to moral objection. We argue that individuals expect those high in legitimate power to engage in moral objection, but expect those low in legitimate power to comply with ethically questionable practices. We further propose that these contrasting role expectations influence the extent to which moral objectors are perceived as warm and subjected to social sanctions (i.e., insults, pressure, unfriendly behavior). We test our predictions with 3 experiments. Study 1, which draws on participants' prior workplace experiences, supports the first section of our mediated moderation model in which the negative association between an actor's moral objection (vs. compliance) and observers' warmth perceptions is weaker when the actor is high rather than low in legitimate power and this effect is mediated by observers' met role expectations. Study 2, an online experiment featuring a biased hiring task, reveals that the warmth perceptions fostered by the Behavior * Legitimate Power interaction influence observers' social sanctioning intentions. Finally, Study 3, a laboratory experiment which exposes participants to unethical behavior in a virtual team task, replicates Study 2's findings and extends the results to actual as well as intended social sanctions. (PsycINFO Database Record PMID- 26882446 TI - Photoacoustic microscopy of arteriovenous shunts and blood diffusion in early stage tumors. AB - Angiogenesis in a tumor region creates arteriovenous (AV) shunts that cause an abnormal venous blood oxygen saturation ( sO2 ) distribution. Here, we applied optical-resolution photoacoustic microscopy to study the AV shunting in vivo. First, we built a phantom to image sO2 distribution in a vessel containing converged flows from two upstream blood vessels with different sO2 values. The phantom experiment showed that the blood from the two upstream vessels maintained a clear sO2 boundary for hundreds of seconds, which is consistent with our theoretical analysis using a diffusion model. Next, we xenotransplanted O-786 tumor cells in mouse ears and observed abnormal sO2 distribution in the downstream vein from the AV shunts in vivo. Finally, we identified the tumor location by tracing the sO2 distribution. Our study suggests that abnormal sO2 distribution induced by the AV shunts in the vessel network may be used as a new functional benchmark for early tumor detection. PMID- 26882447 TI - Imaging and graphing of cortical vasculature using dynamically focused optical coherence microscopy angiography. AB - Recently, optical coherence tomography (OCT) angiography has enabled label-free imaging of vasculature based on dynamic scattering in vessels. However, quantitative volumetric analysis of the vascular networks depicted in OCT angiography data has remained challenging. Multiple-scattering tails (artifacts specific to the imaging geometry) make automated assessment of vascular morphology problematic. We demonstrate that dynamically focused optical coherence microscopy (OCM) angiography with a high numerical aperture, chosen so the scattering length greatly exceeds the depth-of-field, significantly reduces the deleterious effect of multiple-scattering tails in synthesized angiograms. Capitalizing on the improved vascular image quality, we devised and tailored a self-correcting automated graphing approach that achieves a reconstruction of cortical microvasculature from OCM angiography data sets with accuracy approaching that attained by trained operators. The automated techniques described here will facilitate more widespread study of vascular network topology in health and disease. PMID- 26882448 TI - Computational model of bladder tissue based on its measured optical properties. AB - Urinary bladder diseases are a common problem throughout the world and often difficult to accurately diagnose. Furthermore, they pose a heavy financial burden on health services. Urinary bladder tissue from male pigs was spectrophotometrically measured and the resulting data used to calculate the absorption, transmission, and reflectance parameters, along with the derived coefficients of scattering and absorption. These were employed to create a "generic" computational bladder model based on optical properties, simulating the propagation of photons through the tissue at different wavelengths. Using the Monte-Carlo method and fluorescence spectra of UV and blue excited wavelength, diagnostically important biomarkers were modeled. Additionally, the multifunctional noninvasive diagnostics system "LAKK-M" was used to gather fluorescence data to further provide essential comparisons. The ultimate goal of the study was to successfully simulate the effects of varying excited radiation wavelengths on bladder tissue to determine the effectiveness of photonics diagnostic devices. With increased accuracy, this model could be used to reliably aid in differentiating healthy and pathological tissues within the bladder and potentially other hollow organs. PMID- 26882449 TI - Retinal optical coherence tomography at 1 MUm with dynamic focus control and axial motion tracking. AB - High-resolution optical coherence tomography (OCT) retinal imaging is important to noninvasively visualize the various retinal structures to aid in better understanding of the pathogenesis of vision-robbing diseases. However, conventional OCT systems have a trade-off between lateral resolution and depth-of focus. In this report, we present the development of a focus-stacking OCT system with automatic focus optimization for high-resolution, extended-focal-range clinical retinal imaging by incorporating a variable-focus liquid lens into the sample arm optics. Retinal layer tracking and selection was performed using a graphics processing unit accelerated processing platform for focus optimization, providing real-time layer-specific en face visualization. After optimization, multiple volumes focused at different depths were acquired, registered, and stitched together to yield a single, high-resolution focus-stacked dataset. Using this system, we show high-resolution images of the retina and optic nerve head, from which we extracted clinically relevant parameters such as the nerve fiber layer thickness and lamina cribrosa microarchitecture. PMID- 26882450 TI - Evaluation of low-level laser therapy in the treatment of masticatory muscles spasticity in children with cerebral palsy. AB - Spasticity is a motor disorder frequently present in individuals with cerebral palsy (CP). This study aimed to evaluate the effect of low-level laser therapy (LLLT) on the spasticity of the masseter and anterior temporal muscle fibers in children with CP over three weeks of intermittent laser exposures. The bite force (BF) of the masticatory muscles and the amplitude of mouth opening were evaluated before and after laser irradiation in 30 children with CP. Both sides of the masseter and temporalis muscles were irradiated with low-intensity diode laser pulses of 808-nm wavelength six times over three consecutive weeks. During the subsequent three weeks of postlaser exposures, although no laser treatment was applied, the evaluation parameters were measured and recorded. A significant improvement in the amplitude of mouth opening and a decrease in the BF were observed in the weeks following LLLT (P<0.05 ). However, by the sixth week post LLLT, the BF and the amplitude of mouth opening reverted to values equivalent to those obtained before the first application of LLLT. Our investigation revealed low-level energy exposures from a 808-nm diode laser to be an effective short term therapeutic tool. This method increased the amplitude of mouth opening and decreased the muscle tonus of children with spastic CP over a time course of three weeks of intermittent laser applications. PMID- 26882451 TI - Effect of Stem Cell Therapy on Bone Mineral Density: A Meta-Analysis of Preclinical Studies in Animal Models of Osteoporosis. AB - BACKGROUND: Preclinical studies of the therapeutic role of stem cell based therapy in animal models of osteoporosis have largely yielded inconsistent results. We performed a meta-analysis to provide an overview of the currently available evidence. METHODS: Pubmed, Embase and Cochrane Library databases were systematically searched for relevant controlled studies. A random-effect model was used for pooled analysis of the effect of stem cell based therapy on bone mineral density (BMD). Stratified analyses were performed to explore the effect of study characteristics on the outcomes. RESULTS: Pooled results from 12 preclinical studies (110 animals in stem cell treatment groups, and 106 animals in control groups) indicated that stem cell based treatment was associated with significantly improved BMD (standardized mean difference [SMD] = 1.29, 95% Confidence Interval [CI]: 0.84-1.74, P < 0.001) with moderate heterogeneity (Cochrane's Q test: P = 0.02, I2 = 45%) among the constituent studies. Implantation of bone marrow cells, bone marrow mesenchymal stem cells, adipose derived stem cells, and human umbilical cord blood-derived CD34+ cells, were all associated with improved BMD as compared to that in the controls (P < 0.05 for all); the only exception being the use of embryonic stem cell transplantation (P > 0.05). Egger's test detected potential publication bias (P = 0.055); however, 'trim and fill' analysis yielded similar results after statistically incorporating the hypothetical studies in the analysis (SMD = 1.24, 95% CI: 0.32 2.16, P < 0.001). CONCLUSIONS: Stem cell transplantation may improve BMD in animal models of osteoporosis. Our meta-analysis indicates a potential therapeutic role of stem cell based therapy for osteoporosis, and serves to augment the rationale for clinical studies. PMID- 26882452 TI - SOD1 gene polymorphisms in sudden sensorineural hearing loss. AB - CONCLUSION: The results suggest that SOD1 rs4998557 could be associated with susceptibility to SSNHL in the Japanese population. OBJECTIVES: To assess the gene association with sudden sensorineural hearing loss (SSNHL). METHODS: A two stage case control study was conducted to explore the relationship of the candidate genes to SSNHL. The 192 gene samples from SSNHL patients registered in the intractable inner ear disease gene bank were enrolled. As the candidate genes, 39 SNPs from 31 genes were selected for the first stage study. The second stage study examined whether the SOD1 gene polymorphisms, defined by significant differences between cases and controls in the first stage study, are associated with SSNHL. RESULTS: Significant differences were observed in four SNPs from three genes, Glutathione-S-transferase pai 1 (GSTP1), proteine kinase C heta (PRKCH), and superoxide dismutase 1 (SOD1), in terms of allele frequency between SSNHL patients and HapMap controls. In the SOD1 gene, a significant difference was observed in the dominant model study of the SNP rs4998557 in the second stage study. Furthermore, as a result of dividing SSNHL patients based on the clinical data, the difference was more apparent in the case of the over 60 dB group and the tinnitus-positive group. PMID- 26882453 TI - Efficacy of tamoxifen in combination with docetaxel in patients with advanced non small-cell lung cancer pretreated with platinum-based chemotherapy. AB - The aim of this study was to evaluate the efficacy and safety of the combination of docetaxel (TXT) plus tamoxifen (TAM) in advanced non-small-cell lung cancer (NSCLC) patients who had received platinum-based first-line chemotherapy. A total of 120 advanced NSCLC patients pretreated with platinum-based chemotherapy were randomized into two treatment groups (the TXT and TXT+TAM groups) in a 1 : 1 ratio. Reversal of P-glycoprotein (P-gp) expression, tumor response, progression free survival, overall survival, and safety were evaluated on an intention-to treat basis. The median number of cycles of allocated chemotherapy was four in each treatment group (range: 2-6 cycles). The overall response rate and disease control rate in the TXT+TAM group were significantly higher than those in the TXT group (36.7 vs. 15.0% for overall response rate, P=0.007; 85.0 vs. 68.3% for disease control rate, P=0.031). The combination of TXT and TAM could effectively reverse P-gp expression in tumor tissues and provide a significant survival benefit for advanced NSCLC patients compared with TXT alone (11.6 vs. 9.1 months, P=0.030). In addition, in the TXT+TAM group, patients achieving P-gp reversal had a significantly greater median progression-free survival and overall survival than nonreversal patients. Furthermore, the combined therapy showed a safety profile comparable to that of TXT. The combination of TXT and TAM may be an effective and safe treatment option for advanced NSCLC patients who have already developed P-gp-mediated multidrug resistance. PMID- 26882454 TI - Complex Structural and Dynamical Interplay of Cyano-Based Ionic Liquids. AB - We carried out ab initio molecular dynamics simulations for the three cyano-based ionic liquids, 1-ethyl-3-methylimidazolium tetracyanoborate ([C2C1Im][B(CN)4]), 1 ethyl-3-methyl-imidazolium dicyanamide ([C2C1Im][N(CN)2]), and 1-ethyl-3 methylimidazolium thiocyanate ([C2C1Im][SCN]). We found that the [SCN]-based ionic liquid is much more prone to pi-pi stacking interactions as opposed to the other two ionic liquids, contrary to the fact that all liquids bear the same cation. Hydrogen bonding is strong in the dicyanamide- and the thiocyanate-based ionic liquids and it is almost absent in the tetracyanoborate liquid. The anion prefers to stay on-top of the imidazolium ring with the highest priority for the [N(CN)2](-) anion followed by the [B(CN)4](-) anion. We find that experimental viscosity trends cannot be correlated to the hydrogen bond dynamics which is fastest for [B(CN)4](-) followed by [SCN](-) and [N(CN)2](-). For the dynamics of the cation on-top of itself, we find the order of [B(CN)4](-) followed by [N(CN)2](-) and finally by [SCN](-). Interestingly, this trend correlates well with the viscosity, suggesting a relation between the cation-cation dynamics and the viscosity at least for these cyano-based ionic liquids. These findings, especially the apparent correlation between cation-cation dynamics and the viscosity, might be useful for the suggestion of better ionic liquids in electrolyte applications. PMID- 26882455 TI - Interfaces with Tunable Mechanical and Radiosensitizing Properties. AB - We report the fabrication of a composite containing nanostructured GaOOH and Matrigel with tunable radiosensitizing and stiffness properties. Composite characterization was done with microscopy and rheology. The utility of the interface was tested in vitro using fibroblasts. Cell viability and reactive oxygen species assays quantified the effects of radiation dosages and GaOOH concentrations. Fibroblasts' viability decreased with increasing concentration of GaOOH and composite stiffness. During ionizing radiation experiments the presence of the scintillating GaOOH triggered a different cellular response. Reactive oxygen species data demonstrated that one can reduce the amount of radiation needed to modulate the behavior of cells on interfaces with different stiffness containing a radiosensitizing material. PMID- 26882457 TI - Social and emotional self-efficacy at work. AB - Research has shown that self-efficacy is often one of the most important personal resources in the work context. However, because this research has focused on cognitive and task-oriented self-efficacy, little is known about social and emotional dimensions of self-efficacy at work. The main aim of the present study was to investigate social and emotional self-efficacy dimensions at work and to compare them to a cognitive and task-oriented dimension. Scales to measure social and emotional self-efficacy at work were developed and validated and found to be well differentiated from the cognitive task-oriented occupational self-efficacy scale. Confirmatory factor analyses of data from 226 Swedish and 591 German employees resulted in four separate but correlated self-efficacy dimensions: (1) occupational; (2) social; (3) self-oriented emotional; and (4) other-oriented emotional. Social self-efficacy explained additional variance in team climate and emotional self-efficacy in emotional irritation and emotional exhaustion, over and above effects of occupational self-efficacy. Men reported higher occupational self-efficacy, whereas social and emotional self-efficacy revealed no clear gender differences. The scales have strong psychometric properties in both Swedish and German language versions. The positive association between social self-efficacy and team climate, and the negative relationships between self oriented emotional self-efficacy and emotional irritation and emotional exhaustion may provide promising tools for practical applications in work settings such as team-building, staff development, recruitment or other training programs aiming for work place health promotion. The next step will be to study how social and emotional self-efficacy relate to leadership, well-being and health over time. PMID- 26882456 TI - Anthocyanins in Strawberry Polyphenolic Extract Enhance the Beneficial Effects of Diets with Fructooligosaccharides in the Rat Cecal Environment. AB - The administration of fructooligosaccharides (FOS) beneficially modulates gastrointestinal functions and may enhance the metabolism of polyphenols. However, different polyphenolic components in the diet may have different influences on the activities of the digestive enzymes and microbiota in the gastrointestinal tract. Therefore, a 4-week study of forty-eight male Wistar rats was conducted to investigate the physiological response of the rat cecal environment to diets without and with FOS that contained two different strawberry polyphenolic extracts, specifically EP (polyphenolic profile 60, 35, 5, and 0% ellagitannins, proanthocyanidins, flavonols, anthocyanins, respectively) and EPA (polyphenolic profile: 50, 35, 6, and 9%, respectively). When combined with FOS, both extracts beneficially enhanced the acidification of the cecal digesta (P<=0.05 vs the groups without extracts), but the dietary combination of EPA and FOS elicited the greatest reduction in putrefactive short-chain fatty acid production and the lowest fecal beta-glucuronidase activity in the cecum (P<=0.05 vs group EP). Moreover, the addition of dietary FOS elevated the metabolism of the examined strawberry extracts in the cecum and thereby increased the concentrations of the metabolites in the cecal digesta and urine (P<=0.05 vs the group with cellulose). Overall, both strawberry extracts modulated the effects of FOS in the gastrointestinal tract; however, the combination with EPA extract that contained anthocyanins exhibited greater beneficial effects in the lower gut environment than the EP extract. PMID- 26882458 TI - Evolution of the neobladder: A critical review of open and intracorporeal neobladder reconstruction techniques. AB - Orthotopic neobladder is an attractive alternative to the ileal conduit following radical cystectomy. Robotic cystectomy is gaining popularity although the uptake of neobladder reconstruction is low, with the majority of cases being constructed extracorporeally via a mini-laparotomy. Minimally invasive cystectomy using the robotic platform facilitates intracorporeal neobladder reconstruction and several techniques have been described. This review discusses issues relating to patient selection, and describes existing techniques of open surgical neobladder reconstruction and their evolution to suit an intracorporeal approach. A Medline search for publications from January 1970 to September 2015 with the following keyword search criteria was performed: radical cystectomy, robotic cystectomy, intracorporeal, neobladder, orthotopic bladder reconstruction, surgical technique, patient selection and ureteric-ileal anastomosis. PMID- 26882459 TI - Do people with HIV infection have a higher risk of fracture compared with those without HIV infection? AB - PURPOSE OF REVIEW: This review details recent findings that inform the prevalence and incidence of fractures in people living with HIV (PLWH) and examines the effects of HIV infection and antiretroviral therapy (ART), as well as demographics and traditional risk factors on fractures. As antiretroviral guidelines have recently changed to recommend the introduction of ART at diagnosis of HIV infection, the long-term effects of ART on bone health and fracture risk need to be better understood. RECENT FINDINGS: It is apparent that both the effects of HIV infection alone and initiation of ART are associated with significant bone loss in individuals with HIV infection, resulting in osteopenia and osteoporosis. The clinical consequence of low bone mineral density is a greater risk of fragility fractures that are more common in older HIV patients, and those on ART. Frailty occurs at a prevalence of about 10% (about twice that of the general population), and the increased propensity of falls results in greater fracture prevalence, morbidity and mortality. SUMMARY: This review examines data from recent cohort studies and clinical trials to inform a better understanding of the complex relationship between the effects of HIV infection, ART and demographics on fractures in PLWH. PMID- 26882461 TI - Assessing Sample Bias among Venue-Based Respondents at Medical Marijuana Dispensaries. AB - Venue-based sampling is the identification of, and outreach to, locations visited by the population of interest for the purpose of collecting data. The method is frequently used to reach specific populations, commonly referred to as "hidden populations." Medical marijuana users represent a hidden population of persons who use marijuana for medicinal purposes. We examine whether venue-based procedures introduce selection or non-respondent bias into the study. The venue based sampling procedures employed for the UCLA Medical Marijuana Study used a two-stage, venue-based sampling approach. First, analyses were conducted to assess potential bias within dispensaries that agreed to participate in the surveys. Secondly, analyses were conducted to examine differences among patrons who responded to surveys. Overall, selection bias was generally absent among study results. Results also illuminated the minimal respondent bias observed among the survey respondents. Results suggest that the use of dispensaries to access and survey medical marijuana users is a viable option to gather patient information that adequately represents the greater population of medical marijuana users in Los Angeles. Thus, recommendations and conclusions based on findings from venue-based studies of medical marijuana users at dispensary sites serve to impartially inform meaningful research. PMID- 26882462 TI - Power Normalization for Mass Spectrometry Data Analysis and Analytical Method Assessment. AB - Biomarker profiling using mass spectrometry plays an essential role in biological studies and is highly dependent on the data analysis for sample classification. In this study, we introduced power nomination of the mass spectra as a method for systematically altering the weights of peaks at different intensity levels. In combination with the use of support vector machine method (SVM), the impact on the sample classification has been characterized using data in four studies previously reported, including the distinctions of anomeric configurations of sugars, types of bacteria, stages of melanoma, and the types of breast cancer. Comprehensive analysis of the data with normalization at different power normalization index (PNI) was developed and analysis tools, including error-PNI plots, reference profiles, and error source profiles, were used to assess the potential of the analytical methods as well as to find the proper approaches to classify the samples. PMID- 26882460 TI - More than osteoporosis: age-specific issues in bone health. AB - PURPOSE OF REVIEW: The interaction between fall and fracture risk factors is an area of increasing clinical relevance, but little information is known about the age-specific issues in bone health unique to HIV-infected adults. The present review will focus on what is known about falls and fall risk factors among HIV infected adults, and then review the association between decreased muscle, increased adiposity, and frailty with both low bone mineral density (BMD) and falls. RECENT FINDINGS: The rate of falls among middle-aged HIV-infected adults is similar to that of HIV-uninfected adults 65 years and older. Many of the clinical factors that contribute to low BMD overlap with risk factors for falls, resulting in a high risk of a serious fall among older adults with the greatest risk for a fracture. Low muscle mass, increased adiposity and metabolic syndrome, physical function impairment and frailty, common among older HIV-infected adults, contribute to an increased risk for low BMD and falls, and subsequently, may increase the risk of fracture among HIV-infected older adults. SUMMARY: Interventions with dual benefit on reducing fall risk and improving BMD are likely to have the greatest impact on fracture prevention in the older, HIV infected adult. PMID- 26882463 TI - Modeling Transient Disconnections and Compression Artifacts of Continuous Glucose Sensors. AB - BACKGROUND: Modeling the various error components affecting continuous glucose monitoring (CGM) sensors is very important (e.g., to generate realistic scenarios for developing and testing CGM-based applications in type 1 diabetes simulators). Recent work has focused on some error components (i.e., blood-to-interstitium delay, calibration, and random noise), but key events such as transient faults have not been investigated in depth. We propose two mathematical models that describe the disconnections and compression artifacts. MATERIALS AND METHODS: A dataset of 72 subjects monitored with the Dexcom (San Diego, CA) G4((r)) Platinum sensor is considered. Disconnections and compression artifacts have been isolated, and some basic statistical parameters (e.g., frequency and duration) have been extracted. A Markov chain model is proposed to describe the dynamics of a disconnection, and the effect of a compression artifact in the CGM profile is modeled as the output of a first-order linear dynamic system driven by a rectangular function. RESULTS: The great majority of disconnections (approximately 90%) lasted less than 20 min. Compression artifact median (5(th) 95(th) percentiles) values were 45 (30-70) min for the duration and 24 (10-48) mg/dL for the amplitude. Both disconnections and compression artifacts happened with almost equal probability during the 7 days of monitoring. Disconnections were more frequent during the day and compression artifacts during the night. A three-state Markov model is shown to be effective to describe the single disconnection. The asymmetric shape of compression artifact is well fitted by the proposed model. CONCLUSIONS: The provided models are sufficiently accurate for simulation purposes (e.g., to create more challenging and realistic scenarios) to test real-time fault detection algorithms and artificial pancreas closed-loop controllers. PMID- 26882464 TI - Innovation in Analysis of Respiratory Sounds. PMID- 26882465 TI - Modelling exciton-phonon interactions in optically driven quantum dots. AB - We provide a self-contained review of master equation approaches to modelling phonon effects in optically driven self-assembled quantum dots. Coupling of the (quasi) two-level excitonic system to phonons leads to dissipation and dephasing, the rates of which depend on the excitation conditions, intrinsic properties of the QD sample, and its temperature. We describe several techniques, which include weak-coupling master equations that are perturbative in the exciton-phonon coupling, as well as those based on the polaron transformation that can remain valid for strong phonon interactions. We additionally consider the role of phonons in altering the optical emission characteristics of quantum dot devices, outlining how we must modify standard quantum optics treatments to account for the presence of the solid-state environment. PMID- 26882466 TI - The Role of Patients' Stories in Emergency Medicine Triage. AB - Emergency medicine is a communicative activity, and characteristics such as incomplete information, time pressure, and the potentially serious consequences of errors complicate effective communication and decision making. The present study examined the triage process as an interpretive activity driven in part by the patient's story. Of four identified communication processes in the emergency department (ED), the "handoff" of patients between shifts has been identified as especially problematic since missing contextual details from patients' stories increased the probability of errors. The problematic nature of patient handoffs led to our interest in triage, the initial site of interpretation and decision making. Triage distinguishes patients with emergent medical conditions requiring immediate care from those who can more safely wait for medical attention. We report results from 110 hours of observing the triage process and semistructured interviews with 16 triage nurses in a Level I Trauma Center in an urban teaching hospital in the southeastern United States. Field notes and interview transcripts were analyzed and coded to explore decision rules and information sources used in triage decision making. Triage nurses generally discounted patients' stories in favor of information from visual cues and vital signs. Patients' stories tended to influence the triage process only in certain cases when the story contained information that was not readily apparent, such as a recent organ transplant. Triage nurses' reliance on "gut feeling," however, might be a kind of narrative sense-making that combines observable and measurable clinical facts with the narrative competence to utilize intuition and past experience. PMID- 26882467 TI - Testing specificity among parents' depressive symptoms, parenting, and child internalizing and externalizing symptoms. AB - The present study examined the specificity in relations between observed withdrawn and intrusive parenting behaviors and children's internalizing and externalizing symptoms in an at-risk sample of children (ages 9 to 15 years old) of parents with a history of depression (N = 180). Given past findings that parental depression and parenting behaviors may differentially impact boys and girls, gender was examined as a moderator of the relations between these factors and child adjustment. Correlation and linear regression analyses showed that parental depressive symptoms were significantly related to withdrawn parenting for parents of boys and girls and to intrusive parenting for parents of boys only. When controlling for intrusive parenting, preliminary analyses demonstrated that parental depressive symptoms were significantly related to withdrawn parenting for parents of boys, and this association approached significance for parents of girls. Specificity analyses yielded that, when controlling for the other type of problem (i.e., internalizing or externalizing), withdrawn parenting specifically predicted externalizing problems but not internalizing problems in girls. No evidence of specificity was found for boys in this sample, suggesting that impaired parenting behaviors are diffusely related to both internalizing and externalizing symptoms for boys. Overall, results highlight the importance of accounting for child gender and suggest that targeting improvement in parenting behaviors and the reduction of depressive symptoms in interventions with parents with a history of depression may have potential to reduce internalizing and externalizing problems in this high-risk population. PMID- 26882468 TI - Interannual Variability in Baseline Ozone and Its Relationship to Surface Ozone in the Western U.S. AB - Baseline ozone refers to observed concentrations of tropospheric ozone at sites that have a negligible influence from local emissions. The Mount Bachelor Observatory (MBO) was established in 2004 to examine baseline air masses as they arrive to North America from the west. In May 2012, we observed an O3 increase of 2.0-8.5 ppbv in monthly average maximum daily 8-hour average O3 mixing ratio (MDA8 O3) at MBO and numerous other sites in the western U.S. compared to previous years. This shift in the O3 distribution had an impact on the number of exceedance days. We also observed a good correlation between daily MDA8 variations at MBO and at downwind sites. This suggests that under specific meteorological conditions, synoptic variation in O3 at MBO can be observed at other surface sites in the western U.S. At MBO, the elevated O3 concentrations in May 2012 are associated with low CO values and low water vapor values, consistent with transport from the upper troposphere/lower stratosphere (UT/LS). Furthermore, the Real-time Air Quality Modeling System (RAQMS) analyses indicate that a large flux of O3 from the UT/LS in May 2012 contributed to the observed enhanced O3 across the western U.S. Our results suggest that a network of mountaintop observations, LiDAR and satellite observations of O3 could provide key data on daily and interannual variations in baseline O3. PMID- 26882470 TI - Induction of TDO2 and IDO2 in Liver by High-Fat Feeding in Mice: Discrepancies with Human Obesity. AB - Low-grade and chronic inflammation is elicited in white adipose tissue in human obesity. The presence of inflammatory molecules leads to an increased tryptophan catabolism through the induction of indoleamine-2,3-dioxygenase-1 (IDO1). In order to characterize the mechanisms underlying this dysregulation, we have studied 2 mouse models of obesity. Unexpectedly, we did not detect any IDO1 expression in obese or lean mice adipose tissue. In a previous study, we did not find any significant difference in the liver for IDO2 and tryptophan-2,3 dioxygenase (TDO2) gene expression between normal weight and obese patients. IDO2 and TDO2 expression was increased in the liver of high-fat fed mice, but not in ob/ob mice, and was strongly correlated with hydroxysteroid-(11-beta) dehydrogenase-1 (HSD11B1) expression, an enzyme that generates active cortisol within tissues. In conclusion, despite a dysregulation of tryptophan metabolism, obese mice display discrepancies with human obesity metabolism, rendering them inappropriate for further investigations in this animal model. PMID- 26882469 TI - Ambulatory Blood Pressure Monitoring in Individuals with HIV: A Systematic Review and Meta-Analysis. AB - INTRODUCTION: Abnormal diurnal blood pressure (BP) rhythms may contribute to the high cardiovascular disease risk in HIV-positive (HIV+) individuals. To synthesize the current literature on ambulatory BP monitoring (ABPM) in HIV+ individuals, a systematic literature review and meta-analysis were performed. METHODS: Medical databases were searched through November 11, 2015 for studies that reported ABPM results in HIV+ individuals. Data were extracted by 2 reviewers and pooled differences between HIV+ and HIV-negative (HIV-) individuals in clinic BP and ABPM measures were calculated using random-effects inverse variance weighted models. RESULTS: Of 597 abstracts reviewed, 8 studies with HIV+ cohorts met the inclusion criteria. The 420 HIV+ and 714 HIV- individuals in 7 studies with HIV- comparison groups were pooled for analyses. The pooled absolute nocturnal systolic and diastolic BP declines were 3.16% (95% confidence interval [CI]: 1.13%, 5.20%) and 2.92% (95% CI: 1.64%, 4.19%) less, respectively, in HIV+ versus HIV- individuals. The pooled odds ratio for non-dipping systolic BP (nocturnal systolic BP decline <10%) in HIV+ versus HIV- individuals was 2.72 (95% CI: 1.92, 3.85). Differences in mean clinic, 24-hour, daytime, or nighttime BP were not statistically significant. I2 and heterogeneity chi-squared statistics indicated the presence of high heterogeneity for all outcomes except percent DBP dipping and non-dipping SBP pattern. CONCLUSIONS: An abnormal diurnal BP pattern may be more common among HIV+ versus HIV- individuals. However, results were heterogeneous for most BP measures, suggesting more research in this area is needed. PMID- 26882471 TI - ZEB1 Upregulates VEGF Expression and Stimulates Angiogenesis in Breast Cancer. AB - Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor angiogenesis has not been fully examined. Here, we present the novel finding that conditioned medium derived from ZEB1 expressing MDA-MB-231 cells significantly increased the capillary tube formation of human umbilical vein endothelial cells (HUVECs), whereas ZEB1 knockdown by RNA interference had the opposite effect. ZEB1 caused marked upregulation of the expression of vascular endothelial growth factor A (VEGFA) at both mRNA and protein levels. Pre-incubation of HUVECs with anti-VEGFA neutralized antibody attenuated ZEB1-mediated tube formation of HUVECs. In breast cancer tissues, expression of ZEB1 was positively correlated with those of VEGFA and CD31. At the molecular level, ZEB1 activated VEGFA transcription by increasing SP1 recruitment to its promoter, which was mediated via the activation of PI3K and p38 pathways. Using a nude mouse xenograft model, we demonstrated that elevated expression of ZEB1 promotes in vivo tumorigenesis and angiogenesis in breast cancer. Collectively, we found that ZEB1-expressing breast cancer cells increase VEGFA production and thus stimulate tumor growth and angiogenesis via a paracrine mechanism. PMID- 26882472 TI - Artificial micro-swimmers in simulated natural environments. AB - Microswimmers, such as bacteria, are known to show different behaviours depending on their local environment. They identify spatial chemical gradients to find nutrient rich areas (chemotaxis) and interact with shear flows to accumulate in high shear regions. Recently, artificial microswimmers have been developed which mimic their natural counterparts in many ways. One of the exciting topics in this field is to study these artificial motors in several natural settings like the ones bacteria interact with. In this Focus article, we summarize recent observations of artificial swimmers in chemical gradients, shear flows and other interesting natural environments simulated in the lab using microfluidics and nanotechnology. PMID- 26882473 TI - Perception of Graphical Virtual Environments by Blind Users via Sensory Substitution. AB - Graphical virtual environments are currently far from accessible to blind users as their content is mostly visual. This is especially unfortunate as these environments hold great potential for this population for purposes such as safe orientation, education, and entertainment. Previous tools have increased accessibility but there is still a long way to go. Visual-to-audio Sensory Substitution-Devices (SSDs) can increase accessibility generically by sonifying on-screen content regardless of the specific environment and offer increased accessibility without the use of expensive dedicated peripherals like electrode/vibrator arrays. Using SSDs virtually utilizes similar skills as when using them in the real world, enabling both training on the device and training on environments virtually before real-world visits. This could enable more complex, standardized and autonomous SSD training and new insights into multisensory interaction and the visually-deprived brain. However, whether congenitally blind users, who have never experienced virtual environments, will be able to use this information for successful perception and interaction within them is currently unclear.We tested this using the EyeMusic SSD, which conveys whole-scene visual information, to perform virtual tasks otherwise impossible without vision. Congenitally blind users had to navigate virtual environments and find doors, differentiate between them based on their features (Experiment1:task1) and surroundings (Experiment1:task2) and walk through them; these tasks were accomplished with a 95% and 97% success rate, respectively. We further explored the reactions of congenitally blind users during their first interaction with a more complex virtual environment than in the previous tasks walking down a virtual street, recognizing different features of houses and trees, navigating to cross-walks, etc. Users reacted enthusiastically and reported feeling immersed within the environment. They highlighted the potential usefulness of such environments for understanding what visual scenes are supposed to look like and their potential for complex training and suggested many future environments they wished to experience. PMID- 26882474 TI - Cigarette smoke inhibits ROCK2 activation in T cells and modulates IL-22 production. AB - Gene-environment interactions are known to play a key role in the development of rheumatoid arthritis (RA). Exposure to cigarette smoke (CS) is one of the strongest environmental risk factors associated with RA and has been shown to mediate a range of complex immunomodulatory effects from decreased T and B cell activation to depressed phagocytic function. The effects of CS on the function of TH17 cells, one of the key TH effector subsets implicated in RA pathogenesis, are not fully understood. IRF4 is one of the crucial transcription factors involved in TH-17 differentiation and is absolutely required for the production of IL-17 and IL-21 but, interestingly, inhibits the synthesis of IL-22. The production of IL-17 and IL-21 by IRF4 can be augmented by its phosphorylation by the serine threonine kinase ROCK2. Given that CS has been reported to increase ROCK activity in endothelial cells, here we investigated the effects of CS on the ROCK2-IRF4 axis in T cells. Surprisingly, we found that CS leads to decreased ROCK2 activation and IRF4 phosphorylation in T cells. This effect was associated with increased IL-22 production. Using a GEF pull-down assay we furthermore identify ARHGEF1 as a key upstream regulator of ROCK2 whose activity in T cells is inhibited by CS. Thus CS can inhibit the ROCK2-IRF4 axis and modulate T cell production of IL-22. PMID- 26882476 TI - HIV-related stigma and self-disclosure: the mediating and moderating role of anticipated discrimination among people living with HIV/AIDS in Akure Nigeria. AB - Although links between HIV-related stigma and self-disclosure of HIV status among people living with HIV have been well established, it is unclear whether levels of perceived discrimination are differentially associated with self-disclosure. The present study using a multi-factorial survey design investigated the role of stigma and other self-related factors (e.g., anticipated discrimination, self esteem, HIV-related factors [e.g., drug use combination; knowledge of duration of HIV diagnosis] and socio-demographic factors [e.g., multiple spouse; age, gender, educational level] and psychological distress [depression]) in self-disclosure among People living with HIV/AIDs has been added (PLWHA) on follow-up management in State Specialist Hospital Akure, Nigeria. One hundred and thirty nine HIV/AIDS patients (49 males and 90 females) participated in the study. Mean age and mean time in months since diagnosis were 39.56 +/- 10.26 and 37.78 +/- 48.34, respectively. Four variables: multiple spouse, anticipated discrimination, HIV related stigma and self-esteem were related to self-disclosure at (p < .05). Product-term regression analyses demonstrated that perceived discrimination mediated the relationship between self-esteem (Sobel test: z = 2.09, Aroian = 2.06, p < .001), perceived stigma (Sobel test: z = 2.78, Aroaian = 2.75 p < .01) and self-disclosure. Interaction term analysis between HIV-related stigma t (5, 137) = 1.69, p > .05, self-esteem t (5, 137) = .59, p > .05 and anticipated discrimination were non-significant, suggesting a non-moderation effect of discrimination and disclosure. The results indicate that anticipated discrimination may impact HIV-related stigma to reduce self-disclosure among the PLWHAs in Akure, Nigeria. Interventions should incorporate anticipated discrimination in educational programs of HIV stigma in encouraging self disclosure among PLWHAs. PMID- 26882475 TI - ZBIT Bioinformatics Toolbox: A Web-Platform for Systems Biology and Expression Data Analysis. AB - Bioinformatics analysis has become an integral part of research in biology. However, installation and use of scientific software can be difficult and often requires technical expert knowledge. Reasons are dependencies on certain operating systems or required third-party libraries, missing graphical user interfaces and documentation, or nonstandard input and output formats. In order to make bioinformatics software easily accessible to researchers, we here present a web-based platform. The Center for Bioinformatics Tuebingen (ZBIT) Bioinformatics Toolbox provides web-based access to a collection of bioinformatics tools developed for systems biology, protein sequence annotation, and expression data analysis. Currently, the collection encompasses software for conversion and processing of community standards SBML and BioPAX, transcription factor analysis, and analysis of microarray data from transcriptomics and proteomics studies. All tools are hosted on a customized Galaxy instance and run on a dedicated computation cluster. Users only need a web browser and an active internet connection in order to benefit from this service. The web platform is designed to facilitate the usage of the bioinformatics tools for researchers without advanced technical background. Users can combine tools for complex analyses or use predefined, customizable workflows. All results are stored persistently and reproducible. For each tool, we provide documentation, tutorials, and example data to maximize usability. The ZBIT Bioinformatics Toolbox is freely available at https://webservices.cs.uni-tuebingen.de/. PMID- 26882477 TI - Prechemotherapy Touch Sensation Deficits Predict Oxaliplatin-Induced Neuropathy in Patients with Colorectal Cancer. AB - OBJECTIVE: We examined the emergence of chemotherapy-induced peripheral neuropathy (CIPN), a dose-limiting toxicity of oxaliplatin, over the course of oxaliplatin-based chemotherapy for colorectal cancer (CRC). Predicting which patients will likely develop CIPN is an ongoing clinical challenge. METHODS: Oxaliplatin-naive patients with CRC underwent quantitative sensory testing (QST) before beginning oxaliplatin-based chemotherapy and then rated CIPN-related symptoms via the MD Anderson Symptom Inventory (MDASI) weekly for 26 weeks. Mixed modeling examined the value of QST for predicting higher CIPN (MDASI numbness/tingling) during treatment. Trajectory analysis identified a patient subgroup with consistently higher CIPN symptoms. RESULTS: Numbness/tingling was the most frequent, most severe symptom, with 51% of patients clustering into a high CIPN subgroup. Touch sensation deficits (Bumps Detection test) significantly predicted the development of more severe numbness/tingling [estimate (est) = 0.106, p = 0.0003]. The high CIPN subgroup reported increased pain (est = 0.472, p < 0.0001) and interference with walking (est = 0.840, p < 0.0001). In the high CIPN subgroup, patient-reported numbness/tingling worsened rapidly in weeks 0-5 (est = 0.57, p < 0.0001) and then more gradually in weeks 6-26 (est = 0.07, p < 0.0001). CONCLUSION: Prechemotherapy screening with a simple, easily administered objective measure of touch sensation deficits (Bumps Detection test) and monitoring of patient-reported numbness/tingling during the first 2-3 chemotherapy cycles may support improved personalized care of CRC patients with oxaliplatin-induced CIPN. PMID- 26882478 TI - Intraoperative OCT Pachymetry in Patients Undergoing Dextran-Free Riboflavin UVA Accelerated Corneal Collagen Crosslinking. AB - PURPOSE: To assess intraoperative corneal pachymetry in patients undergoing accelerated corneal collagen crosslinking with a dextran-free riboflavin solution. METHODS: Prospective, non-comparative, multicenter interventional study. Thirty patients with progressive keratoconus were enrolled in the study from the Siena Crosslinking CenterTM in Siena, Italy and the Eye Center in Catanzaro, Italy. The mean age was 26.9 +/- 6.5 years. Patients underwent pulsed light accelerated crosslinking (PL-ACXL) by KXL I UV-A source (Avedro Inc., Waltham, MS, USA) with 8 min (1 s on/1 s off) of UV-A exposure, 30 mW/cm2 and an energy dose of 7.2 J/cm2. Corneal stroma was soaked with a dextran-free 0.1% riboflavin solution plus hydroxyl-propyl methylcellulose (HPMC) (VibeX Rapid, Avedro). Intraoperative corneal thickness was preoperatively (PRE-OP) evaluated by corneal optical coherence tomography (iVUE Optovue Inc., Fremont, CA, USA) after epithelium removal (EPI-R), after 10 min of riboflavin soaking (RS) and after UV-A irradiation (IR). Statistical analysis was conducted using a Wilcoxon test and SPSS v16.0. A p-value of <0.05 was considered to be statistically significant. RESULTS: Average PRE-OP central corneal thickness (CCT) and thinnest corneal thickness (TCT) were 437.3 +/- 36.9 and 418.9 +/- 28.8 MUm, respectively. Average EPI-R CCT and TCT values were 388.5 +/- 36.8 and 381.5 +/- 36.61 MUm, respectively. Average CCT and TCT values after 10 min RS were 385.2 +/- 37.8 and 380.6 +/- 36.7 MUm, respectively. The final average CCT and TCT values after IR were 379.4 +/- 37.2 and 378.1 +/- 36.4 MUm, respectively. CONCLUSIONS: The study demonstrated a non-statistically significant intraoperative corneal thickness reduction in patients undergoing PL-ACXL corneal collagen crosslinking by using dextran free HPMC 0.1% riboflavin solution. PMID- 26882479 TI - Worldwide Alien Invasion: A Methodological Approach to Forecast the Potential Spread of a Highly Invasive Pollinator. AB - The ecological impacts of alien species invasion are a major threat to global biodiversity. The increasing number of invasion events by alien species and the high cost and difficulty of eradicating invasive species once established require the development of new methods and tools for predicting the most susceptible areas to invasion. Invasive pollinators pose serious threats to biodiversity and human activity due to their close relationship with many plants (including crop species) and high potential competitiveness for resources with native pollinators. Although at an early stage of expansion, the bumblebee species Bombus terrestris is becoming a representative case of pollinator invasion at a global scale, particularly given its high velocity of invasive spread and the increasing number of reports of its impacts on native bees and crops in many countries. We present here a methodological framework of habitat suitability modeling that integrates new approaches for detecting habitats that are susceptible to Bombus terrestris invasion at a global scale. Our approach did not include reported invaded locations in the modeling procedure; instead, those locations were used exclusively to evaluate the accuracy of the models in predicting suitability over regions already invaded. Moreover, a new and more intuitive approach was developed to select the models and evaluate different algorithms based on their performance and predictive convergence. Finally, we present a comprehensive global map of susceptibility to Bombus terrestris invasion that highlights priority areas for monitoring. PMID- 26882480 TI - Ectopic Immature Renal Tissue Associated with Lipomeningomyelocele and Enteric Duplication Cyst: A Report of Two Cases. AB - Ectopic immature renal tissue (EIRT) is a lesion rarely described in the literature. It shows the components of a nephrogenic rest including the blastema, epithelia, and stroma. We report two cases of EIRT in a 3-year-old female and an 8 months male child, associated with lipomeningomyelocele and an enteric duplication cyst, respectively, along with detailed immunohistochemical profile. Though there are a few cases of EIRT associated with teratoma, only two cases of EIRT associated with lipomeningomyelocele have been described in the English literature. Moreover, extensive literature search did not reveal any previous case report where EIRT had been documented in an enteric duplication cyst. PMID- 26882481 TI - Pseudoenhancement of Gallbladder Sludge: A Confusing Artifact Caused by Nonlinear Propagation of Ultrasound Through Microbubbles. PMID- 26882482 TI - The Problem of Mammographic Breast Density - The Position of the DEGUM Working Group on Breast Ultrasound. AB - Mammographic breast density correlates with breast cancer risk and also with the number of false-negative calls. In the USA these facts lead to the "Breast Density and Mammography Reporting Act" of 2011. In the case of mammographically dense breasts, the Working Group on Breast Ultrasound in Germany recommends explaining the advantages of adjunct imaging to women, depending on the individual breast cancer risk. Due to the particular structure of German healthcare, quality-assured breast ultrasound would be the first choice. Possible overdiagnosis, costs, potentially increased emotional stress should be addressed. In high familial breast cancer risk, genetic counselling and an intensified early detection program should be performed. PMID- 26882483 TI - Simulation-Based Abdominal Ultrasound Training - A Systematic Review. AB - PURPOSE: The aim is to provide a complete overview of the different simulation based training options for abdominal ultrasound and to explore the evidence of their effect. MATERIALS AND METHODS: This systematic review was performed according to the PRISMA guidelines and Medline, Embase, Web of Science, and the Cochrane Library was searched. Articles were divided into three categories based on study design (randomized controlled trials, before-and-after studies and descriptive studies) and assessed for level of evidence using the Oxford Centre for Evidence Based Medicine (OCEBM) system and for bias using the Cochrane Collaboration risk of bias assessment tool. RESULTS: Seventeen studies were included in the analysis: four randomized controlled trials, eight before-and after studies with pre- and post-test evaluations, and five descriptive studies. No studies scored the highest level of evidence, and 14 had the lowest level. Bias was high for 11 studies, low for four, and unclear for two. No studies used a test with established evidence of validity or examined the correlation between obtained skills on the simulators and real-life clinical skills. Only one study used blinded assessors. CONCLUSION: The included studies were heterogeneous in the choice of simulator, study design, participants, and outcome measures, and the level of evidence for effect was inadequate. In all studies simulation training was equally or more beneficial than other instructions or no instructions. Study designs had significant built-in bias and confounding issues; therefore, further research should be based on randomized controlled trials using tests with validity evidence and blinded assessors. PMID- 26882484 TI - Cost-utility of albiglutide versus insulin lispro, insulin glargine, and sitagliptin for the treatment of type 2 diabetes in the US. AB - Objective To compare the cost-utility of the glucagon-like peptide-1 receptor agonist albiglutide with those of insulin lispro (both in combination with insulin glargine), insulin glargine, and the dipeptidyl peptidase-4 inhibitor sitagliptin, representing treatments along the type 2 diabetes treatment continuum. Methods The Centre for Outcomes Research and Effectiveness (CORE) Diabetes Model was used for the cost-utility analysis. Data from three Phase 3 clinical trials (HARMONY 6, HARMONY 4, and HARMONY 3) evaluating albiglutide for the treatment of patients with type 2 diabetes were used for the baseline characteristics and treatment effects. Utilities and costs were derived from published sources. Results Albiglutide treatment was associated with an improvement in mean quality-adjusted life expectancy of 0.099, 0.033, and 0.101 years when compared with insulin lispro, insulin glargine, and sitagliptin, respectively. Over the 50-year time horizon, mean total costs in the albiglutide arm were $4332, $2597, and $2223 more than in the other respective treatments. These costs resulted in an incremental cost-utility ratio of $43,541, $79,166, and $22,094 per quality-adjusted life-year (QALY) gained for albiglutide vs insulin lispro, insulin glargine, and sitagliptin, respectively. At a willingness to-pay threshold of $50,000 per QALY gained, there was a 53.0%, 41.5%, and 67.5% probability of albiglutide being cost-effective compared with the other respective treatments. Limitations This analysis was an extrapolation over a 50 year time horizon based on relatively short-term data obtained during clinical trials. It does not take into account potential differences between the respective treatments in adherence and persistence that can influence both effects and costs. Conclusions Albiglutide represents a reasonable treatment option for patients with type 2 diabetes based on its cost-utility, relative to insulin lispro, insulin glargine, and sitagliptin. PMID- 26882485 TI - Epidemiological study of traumatic spinal cord injuries: experience from a specialized spine center in Iran. AB - STUDY DESIGN: A cross-sectional study. OBJECTIVES: This study was performed for epidemiological assessment of Iranian Traumatic Spinal Cord Injuries (TSCI), referred to a specialized spine center. SETTING: Patient recruitment and evaluations were conducted at the Brain and Spinal Injury Research Center, Tehran, Iran. METHODS: This study was performed from September 2011 to March 2015 on 1137 consecutive TSCIs. History, clinicoradiological findings as well as chronic complications and social integration were recorded. The capture-recapture method was used to calculate a rough estimation of TSCI prevalence in Tehran Province. RESULTS: Our report includes 1137 cases with a mean age of 29.1 years (s.d.=11.2 year)-79.2% of them being male (M/F=3.8/1). Rough estimation of TSCI prevalence in Tehran province was 2.36 per 10 000 population. Regarding etiology, 61.8% were due to motor vehicle accident (MVA), followed by falling 24.5%, heavy drop 5.2%, violence 3.8%, sport 2.8% and others causes 1.9%. Regarding injury level, 31.5% were cervical, 57.9% thoracic and 10.6% lumbar. Complete lesions were 53.5% of patients and 46.5% were incomplete. Most common neurological type was T1-S5 (American Spinal Injury Association Impairment Scale: A, B, C, 61.7%). Most common complications included urinary tract infection followed by pressure sore (grade III and IV, 37.5%), autonomic dysreflexia (37%) and neuropathic pain (31.2%). Substance abuse was observed in 8.8% of cases. Overall, ~25% in our cases were employed after TSCI. Secondary divorce was also much more frequent than normal matched controls. CONCLUSION: MVA was the most common cause for TSCI. The elderly subjects were less frequent among our patients than more developed countries. The high rate of unemployment and divorce in our cases deserves special consideration. PMID- 26882486 TI - Blood stream infections due to multidrug-resistant organisms among spinal cord injured patients, epidemiology over 16 years and associated risks: a comparative study. AB - STUDY DESIGN: Retrospective study. OBJECTIVES: We aimed to describe the epidemiology of multidrug-resistant organisms (MDROs) during bloodstream infection (BSI) and identify associated risks of MDROs among patients with spinal cord injury (SCI). SETTING: A teaching hospital, expert center in disability, in France. METHODS: We studied a retrospective cohort of all BSIs occurring in SCI patients hospitalized over 16 years. We described the prevalence of MDRO BSI among this population and its evolution over time and compared the BSI population due to MDROs and due to non-MDROs. RESULTS: A total of 318 BSIs occurring among 256 patients were included in the analysis. The most frequent primary sites of infection were urinary tract infection (34.0%), pressure sore (25.2%) and catheter line-associated bloodstream infection (11.3%). MDROs were responsible for 41.8% of BSIs, and this prevalence was stable over 16 years. No significant associated factor for MDRO BSI could be identified concerning sociodemographic and clinical characteristics, primary site of infection and bacterial species in univariate and multivariate analyses. BSI involving MDROs was not associated with initial severity of sepsis compared with infection without MDROs (43.8 vs 43.6%, respectively) and was not associated either with 30th-day mortality (6.2 vs 9%, respectively). CONCLUSION: During BSI occurrence in an SCI population, MDROs are frequent but remain stable over years. No associated risk can be identified that would help optimize antibiotic treatment. Neither the severity of the episode nor the mortality is significantly different when an MDRO is involved. PMID- 26882487 TI - Reliability of the radiographic variables in the International Spinal Cord Injury Spinal Column Injury Basic Data Set compared with the AO classification. AB - STUDY DESIGN: Intra- and interrater reliability study for radiological variables of the International Spinal Cord Injury (SCI) Spinal Column Injury Basic Data Set. OBJECTIVES: To test reliability of the radiological variables in the International SCI Spinal Column Injury Basic Data Set and compare it with the Arbeitsgemeinschaft fur Osteosynthesefragen (AO) classification. SETTING: The database of Eastern Denmark Regional SCI Referral Center, Copenhagen, Denmark. METHODS: Ratings of the International SCI Spinal Column Injury Basic Data Set radiological variables and AO classification were obtained by two international observers for all the surgically treated spine trauma patients between 1st October 2010 and 31st December 2012 at the Spine Unit, Rigshospitalet, Denmark. Statistical analyses for intra- and interrater crude agreement and Cohen's unweighted kappa (kappa) coefficients were performed. RESULTS: For 283 spine injuries, the intra- and interrater reliability for the individual radiological variables of the International SCI Spinal Column Injury Basic Data Set was at least substantial (kappa=0.67-0.97 for interrater, kappa=0.79-0.89 for the intrarater agreement). For the AO classification, intrarater reliability was moderate-to-substantial (kappa=0.57-0.75), whereas interrater reliability was substantial (kappa=0.67-0.69). The crude intra- and interrater agreement for a combined radiographic SCI Spinal Column Injury Basic Data Set variable showed no significant difference compared with the AO classification (P=0.067-0.895). CONCLUSIONS: The reliability of International SCI Spinal Column Injury Basic Data Set radiological variables is comparable to the AO classification system. We encourage its use for spinal column injury description, thus facilitating data collection and comparison between centres and countries. PMID- 26882488 TI - Active paraplegics are protected against exercise-induced oxidative damage through the induction of antioxidant enzymes. AB - STUDY DESIGN: Experimental study. OBJECTIVES: Exercise improves functional capacity in spinal cord injury (SCI). However, exhaustive exercise, especially when sporadic, is linked to the production of reactive oxygen species that may have a detrimental effect on SCI. We aimed to study the effect of a single bout of exhaustive exercise on systemic oxidative stress parameters and on the expression of antioxidant enzymes in individuals with paraplegia. SETTING: The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. METHODS: Sixteen paraplegic subjects were submitted to a graded exercise test (GET) until volitional exhaustion. They were divided into active or non-active groups. Blood samples were drawn immediately, 1 and 2 h after the GET. We determined plasma malondialdehyde (MDA) and protein carbonylation as markers of oxidative damage. Antioxidant gene expression (catalase and glutathione peroxidase-GPx) was determined in peripheral blood mononuclear cells. RESULTS: We found a significant increase in plasma MDA and protein carbonyls immediately after the GET (P<0.05). This increment correlated significantly with the lactate levels. Active paraplegics showed lower levels of exercise-induced oxidative damage (P<0.05) and higher exercise-induced catalase (P<0.01) and GPx (P<0.05) gene expression after the GET. CONCLUSIONS: These results suggest that exercise training may be useful in SCI patients to develop systemic antioxidant defenses that may protect them against exercise-induced oxidative damage. PMID- 26882489 TI - Therapeutic potential of human olfactory bulb neural stem cells for spinal cord injury in rats. AB - STUDY DESIGN: Adult human olfactory bulb neural stem cells (OBNSCs) were isolated from human patients undergoing craniotomy for tumor resection. They were genetically engineered to overexpresses green fluorescent protein (GFP) to help trace them following engraftment. Spinal cord injury (SCI) was induced in rats using standard laminectomy protocol, and GFP-OBNSC were engrafted into rat model of SCI at day 7 post injury. Three rat groups were used: (i) Control group, (ii) Sham group (injected with cerebrospinal fluid) and treated group (engrafted with OBNSCs). Tissues from different groups were collected weekly up to 2 months. The collected tissues were fixed in 4% paraformaldehyde, processed for paraffin sectioning, immunohistochemically stained for different neuronal and glial markers and examined with bright-field fluorescent microscopy. Restoration of sensory motor functions we assessed on a weekly bases using the BBB score. OBJECTIVES: To assess the therapeutic potential of OBNSCs-GFP and their ability to survive, proliferate, differentiate and to restore lost sensory motor functions following their engraftment in spinal cord injury (SCI). METHODS: GFP OBNSC were engrafted into a rat model of SCI at day 7 post injury and were followed-up to 8 weeks using behavioral and histochemical methods. RESULTS: All transplanted animals exhibited successful engraftment. The survival rate was about 30% of initially transplanted cells. Twenty-seven percent of the engrafted cells differentiated along the NG2 and O4-positive oligodendrocyte lineage, 16% into MAP2 and beta-tubulin-positive neurons, and 56% into GFAP-positive astrocytes. CONCLUSION: GFP-OBNSCs had survived for >8 weeks after engraftment and were differentiated into neurons, astrocytes and oligodendrocytes, The engrafted cells were distributed throughout gray and white matter of the cord with no evidence of abnormal morphology or any mass formation indicative of tumorigenesis. However, the engrafted cells failed to restore lost sensory and motor functions as evident from behavioral analysis using the BBB score test. PMID- 26882490 TI - Efficacy and safety of phosphodieterase-5 inhibitors for treatment of erectile dysfunction secondary to spinal cord injury: a systemic review and meta-analysis. AB - STUDY DESIGN: Systemic reviewObjective:We carried out a systematic review and meta-analysis to assess the efficacy and safety of phosphodieterase-5 (PDE5) inhibitors on erectile dysfunction (ED) secondary to spinal cord injury (SCI). METHODS: A literature review was performed to identify all published randomized, double-blind, placebo-controlled trials of PDE5 inhibitors for treatment of ED secondary to SCI. The search included the following database: MEDLINE, EMBASE and the Cochrane Library. The outcomes and complications analyzed involved the Global Efficacy Question (GEQ), sexual encounter profile diary question 2 and 3 (SEP2 and SEP3) and adverse events. All statistical analysis was performed using Stata 12.0 software (Stata Corp., College Station, TX, USA). RESULTS: Six publications were used in analysis, including six randomized controlled trials that compared PDE5 inhibitors with placebo. Compared with placebo, PDE5 inhibitors were associated with significant improvements in GEQ (OR 11.997, 95% CI 8.073-17.830, P<0.0001), SEP2 (RR 1.847, 95% CI 1.561-2.185, P<0.0001) and SEP3 (RR 2.738, 95% CI 2.084-3.598, P<0.0001). Despite significant greater incidences of some adverse events observed (headache: RR 3.717, 95% CI 2.309-5.982, P<0.0001; flushing: RR 9.281, 95% CI 2.858-30.147, P<0.0001; gastrointestinal discomfort: RR 9.064, 95% CI 2.116-38.827, P=0.003), most adverse events were mild to moderate and transient. CONCLUSIONS: This systematic review and meta-analysis indicate that PDE5 inhibitors are effective and well tolerated to treat ED secondary to SCI compared with placebo, as measured by response to GEQ, SEP2, SEP3 and incidence of adverse events. PDE5 inhibitors could be considered as the first choice in the treatment of ED patients with SCI. PMID- 26882491 TI - Electrocardiographic abnormalities in the early stage following traumatic spinal cord injury. AB - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Although cardiac arrhythmias are relatively well recognized in the chronic stage after spinal cord injury (SCI), little is known regarding its occurrence during the early stage. The objective of this study was to examine electrocardiogram changes within the first 72 h after acute traumatic SCI. SETTING: Acute spine trauma center, Toronto, Ontario, CanadaMethods:This study included all consecutive patients with spine trauma admitted to our institution from January 1998 to June 2007 who had an electrocardiogram within the first 72 h post trauma. Patients were divided into four groups: (I) patients with motor complete SCI at T6 or above; (II) patients with motor incomplete SCI at T6 or above; (III) patients with spine trauma but no/minor SCI at T6 or above; and (IV) patients with SCI below T6. RESULTS: There were 69 men and 20 women with mean age of 53.8 years (16-88 years). All groups were comparable regarding age, sex, pre-existing comorbidities and cause of SCI. There were no significant differences among the groups regarding predominant rhythm, PR interval, atrial-ventricular conduction, ventricular rate, QRS axis and intraventricular conduction abnormalities. Nonetheless, patients in Group I had longer RR interval (P=0.016), longer QTc (P=0.025) and more prolonged duration of the longest QRS (P=0.017) in comparison with the other groups. CONCLUSIONS: Our results indicate that electrocardiogram abnormalities are more common within the first 72 h following acute traumatic, motor complete, cervical or high-thoracic SCI. This may represent early manifestations of autonomic dysfunction due to disruption of descending cardiovascular pathways in individuals with severe SCI at T6 or above. PMID- 26882492 TI - Spinal cord injury without radiographic abnormality (SCIWORA) in adults: MRI type predicts early neurologic outcome. AB - OBJECTIVES: The present study aimed to analyse the clinical and neuroimaging features of a consecutive series of adult patients with spinal cord injury without radiographic abnormality (SCIWORA) receiving early magnetic resonance imaging (MRI), and to apply the recently proposed MRI classification system. METHODS: Grade of neurologic impairment at admission and discharge was reported according to the American Spinal Injury Association Impairment Scale (AIS). A detailed analysis and categorisation of the extra- and intramedullary MRI findings was performed, and the relationship between imaging type and neurological outcome was described. RESULTS: Twenty-six adult patients (17 male and 9 female) with SCIWORA were identified (mean age of 52 years). The distribution of the initial AIS grade was 8% A (n=2), 19% B (n=5), 31% C (n=8) and 42% D (n=11) at admission and 15% (n=4) C, 58% (n=15) D and 27% (n=7) E at discharge, respectively. Type I SCIWORA was found in 23% (n=6) and type II in 77% (n=20) (IIa: 0%, IIb: 25%, IIc: 75%). The mean improvement of AIS grade in patients with type I lesions was 1.5 (median 1, range 1-3) and 0.9 (median 1, range 0-3) in type II. CONCLUSION: The findings underline the prognostic role of early MRI for adult patients with SCIWORA and support the use of the recently introduced MRI classification system. LEVEL OF EVIDENCE: Prognostic study, level III. PMID- 26882494 TI - Editorial: Therapeutic Modulators of Cellular Senescence: Common Targets in Cancer And Aging. PMID- 26882493 TI - The relationship between anxiety, depression and religious coping strategies and erectile dysfunction in Iranian patients with spinal cord injury. AB - OBJECTIVES: To assess the role of anxiety, depressive mood and religious coping in erectile function among Iranian patients with spinal cord injury (SCI). SETTING: Brain and Spinal Cord Injury Repair Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. METHODS: A sample of N=93 men with SCI participated in this cross-sectional study. Levels of anxiety and depressive mood were assessed using the Hospital Anxiety and Depression Scale. Religious coping strategies were measured using the 14-items Brief Coping Questionnaire. Erectile function was assessed using the International Index of Erectile Function. The joint effect of anxiety, depressive mood and religious coping strategies on erectile function was assessed by performing stepwise multiple linear regression analyses. RESULTS: The mean age of the SCI patients was 37.8 years with a mean post-injury time of 4.6 years. Multivariate regression analyses indicated that age (B=-0.27, 95% CI=-0.47 to 0.07), education (B for higher education=0.63, 95% CI=0.24 to 1.02), the American Spinal Injury Association impairment scale (B for complete impairment=-3.36, 95% CI=-3.82 to -2.89), anxiety (B=-3.56, 95% CI=-5.76 to -1.42), positive religious coping (B=0.30, 95% CI=0.03 to 0.57), negative religious coping (B=-0.56, 95% CI= 0.82 to -0.29) and the duration of injury (B=-0.25, 95% CI=-0.22 to -0.29) were all independent factors influencing erectile function in SCI patients. CONCLUSION: Overall, the results indicated that SCI patients who use positive religious coping strategies had better erectile function compared with individuals who applied negative religious coping strategies. Furthermore, higher levels of anxiety, greater impairment and longer duration of injury turned out to be risk factors for erectile dysfunction. PMID- 26882495 TI - Abnormal White Matter Integrity in Elderly Patients with Idiopathic Normal Pressure Hydrocephalus: A Tract-Based Spatial Statistics Study. AB - We investigated white matter integrity utilizing diffusion tensor imaging in patients with idiopathic normal-pressure hydrocephalus (INPH) who had a positive response to the cerebrospinal fluid tap test and in age- and gender-matched Alzheimer's disease (AD) patients. We enrolled 28 patients with INPH, 28 patients with AD and 20 healthy controls. Tract-based spatial statistics demonstrated that INPH patients had lower fractional anisotropy (FA) in the anterior corona radiate (bilateral), corpus callosum, superior longitudinal fasciculus (bilateral), posterior thalamic radiation (bilateral), external capsule (bilateral) and middle cerebellar peduncle in comparison with the AD and control groups. Volume-of interest analysis revealed that INPH patients, when compared to the AD and control groups, showed higher mean diffusivity in the anterior corona radiate (bilateral), corpus callosum, superior longitudinal fasciculus (bilateral), posterior thalamic radiation (left), external capsule (bilateral) and middle cerebellar peduncle. And gait dysfunction was significantly correlated with decreased FA in the splenium of the corpus callosum and right external capsule in INPH patients. Our findings may suggest a possibility for considering microstructural changes in white matter integrity in elderly patients as potential imaging markers for differentiation between INPH and AD and may help us understand the potential pathophysiology of gait disturbances associated with INPH. PMID- 26882496 TI - Novel dose-finding designs and considerations on practical implementations in oncology clinical trials. AB - One of the main objectives in phase I oncology trials is to evaluate safety and tolerability of an experimental treatment by estimating the maximum tolerated dose (MTD) based on the rate of dose-limiting toxicities (DLT). To meet emerging challenges in dose-finding studies, over the past two decades, extensive research has been conducted by statistical and medical researchers to create innovative dose finding designs that perform better than the standard 3 + 3 design, which often exhibits undesirable statistical and operational properties. However, clinical implementation and practical usage of these new designs have been limited. This article begins with a review of the most recent literature and then provides some perspectives on implementing novel adaptive dose finding designs in oncology phase I trials from a pharmaceutical industry perspective. Statistical planning and logistical considerations on how to effectively execute such designs in multi-center clinical trials are discussed using two recent case studies. PMID- 26882498 TI - Novel Carbon-Encapsulated Porous SnO2 Anode for Lithium-Ion Batteries with Much Improved Cyclic Stability. AB - Porous SnO2 submicrocubes (SMCs) are synthesized by annealing and HNO3 etching of CoSn(OH)6 SMCs. Bare SnO2 SMCs, as well as bare commercial SnO2 nanoparticles (NPs), show very high initial discharge capacity when used as anode material for lithium-ion batteries. However, during the following cycles most of the Li ions previously inserted cannot be extracted, resulting in considerable irreversibility. Porous SnO2 cubes have been proven to possess better electrochemical performance than the dense nanoparticles. After being encapsulated by carbon shell, the obtained yolk-shell SnO2 SMCs@C exhibits significantly enhanced reversibility for lithium-ions storage. The reversibility of the conversion between SnO2 and Sn, which is largely responsible for the enhanced capacity, has been discussed. The porous SnO2 SMCs@C shows much increased capacity and cycling stability, demonstrating that the porous SnO2 core is essential for better lithium-ion storage performance. The strategy introduced in this paper can be used as a versatile way to fabrication of various metal oxide-based composites. PMID- 26882499 TI - Why Don't Our Patients with Chronic Obstructive Pulmonary Disease Listen to Us? The Enigma of Nonadherence. AB - Nonadherence--not taking pharmacologic or nonpharmacologic treatments according to agreed recommendations from a health care provider--is common in patients with chronic obstructive pulmonary disease. Nonadherence in taking maintenance medications, smoking cessation, maintaining regular physical activity and exercise, starting and staying in pulmonary rehabilitation and continuing on with the postrehabilitation exercise/activity prescription, and successfully following self-management directions results in adverse outcomes across multiple areas. These include a faster decline in airway function, higher symptom burden, impaired health status, and increased health care use and mortality risk. Although nonadherence can also occur in health care providers (not following established treatment guidelines), this perspective focuses on patient nonadherence. Factors such as social/economic, health system, therapy-related, patient-related, and condition-related factors all impact this problem. To improve patient adherence, we need to consider these factors in the context of people with chronic obstructive pulmonary disease and implement strategies directly targeting underlying issues. Strategies may include customizing and simplifying learning and intervention regimes, identifying barriers to adherence and addressing them, ensuring patient support structures are in place, and improving self-efficacy. Future directions should focus on research and development in educational design; use of technology to assist education; psychological intervention strategies to support learning, motivation, self efficacy and behavior change; and ways to improve healthcare providers' engagement with patients. PMID- 26882497 TI - Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests. AB - The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C). Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1(Mph1) kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1(Mph1) kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We show biochemically that Mad3 phospho-mimics are potent APC/C inhibitors in vitro, demonstrating that Mad3p modification can directly influence Cdc20(Slp1)-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests. PMID- 26882500 TI - Impulsive lifestyle counseling to prevent dropout from treatment for substance use disorders in people with antisocial personality disorder: A randomized study. AB - Patients with antisocial personality disorder in outpatient treatment for substance use disorders are at high risk of drop-out. Using a randomized design, this study tested the impact of adding a brief psycho-educational program, the Impulsive Lifestyle Counseling program, to outpatient substance abuse treatment in order to prevent treatment dropout. Patients (N=175) were recruited from 13 municipal treatment centers in Denmark, and assigned to treatment as usual or to the experimental condition. In all, 172 patients could be included in the analyses. In the intent-to-treat analysis, the risk of treatment dropout was reduced among patients randomized to the experimental program (hazard ratio=0.63, p=.031), after controlling for age, gender, and substitution treatment status. The study supported the efficacy of the Impulsive Lifestyle Counseling program as a method for preventing treatment dropout for patients with comorbid antisocial personality disorder in substance abuse treatment. Trial registration #ISRCTN67266318. PMID- 26882501 TI - Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from 'Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma' by Castellarin and colleagues published in Genome Research in 2012 (Castellarin et al., 2012). The experiment to be replicated is reported in Figure 2. Here, Castellarin and colleagues performed a metagenomic analysis of colorectal carcinoma (CRC) to identify potential associations between inflammatory microorganisms and gastrointestinal cancers. They conducted quantitative real time PCR on genomic DNA isolated from tumor and matched normal biopsies from a patient cohort and found that the overall abundance of Fusobacterium was 415 times greater in CRC versus adjacent normal tissue. These results confirmed earlier studies and provide evidence for a link between tissue-associated bacteria and tumorigenesis. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife. PMID- 26882502 TI - More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1. AB - In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistance mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here, we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely. PMID- 26882504 TI - Outpatient Minimally Invasive Lumbar Interbody: Fusion Predictive Factors and Clinical Results. AB - STUDY DESIGN: Retrospective review of data from a prospective patient outcomes registry. OBJECTIVE: The object of this work was to examine patient and surgical predictors of early postoperative discharge and test the predictive model against two clinical series of outpatient minimally invasive lumbar fusion patients. SUMMARY OF BACKGROUND DATA: Outpatient and ambulatory surgery centers are regularly utilized for procedures with low-risk profiles and minimal need for extended postoperative observation, but little has been reported in lumbar spinal fusion producers. METHODS: Two analyses were undertaken, an examination of patient characteristics to determine predictors of early (<24 hours) postoperative discharge and then clinical examinations of patients treated with lumbar fusion at an ambulatory surgery center. For the predictive arm of the study, 1033 patients treated with minimally invasive (MIS) lateral interbody fusion (XLIF) were grouped according to length of postoperative hospitalization with 873 patients discharged <24 hours (outpatients), and 160 discharged >23 hours after surgery (inpatients). For the clinical studies, 54 consecutive XLIF and 18 consecutive MIS posterior fusion patients were treated at an ambulatory surgery center with demographic, treatment, and complication data collected. RESULTS: From the predictive study, the strongest baseline predictors of early postoperative discharge were a less advanced diagnosis (non-deformity), younger age, elevated baseline hemoglobin levels, and lower body mass index. The most predictive treatment variables that predicted early postoperative discharge were fewer number of levels treated and elevated postoperative hemoglobin levels.In the clinical series, outpatient surgeries were performed in younger patients (50.6 and 53.2 yr), at relatively few levels (96% of cases were at one or two levels), for simple degenerative disease. No intraoperative and few postoperatives complications were seen in either XLIF or MIS posterior fusions performed in ambulatory settings with no emergent transfers to inpatient facilities. CONCLUSION: Select patients, by health and indication, can safely be treated as outpatients with XLIF or other modern MIS approaches. Being younger, having elevated preoperative hemoglobin levels, fewer levels being treated, for less advanced disease may predict early postoperative discharge. LEVEL OF EVIDENCE: 3. PMID- 26882503 TI - An external sodium ion binding site controls allosteric gating in TRPV1 channels. AB - TRPV1 channels in sensory neurons are integrators of painful stimuli and heat, yet how they integrate diverse stimuli and sense temperature remains elusive. Here, we show that external sodium ions stabilize the TRPV1 channel in a closed state, such that removing the external ion leads to channel activation. In studying the underlying mechanism, we find that the temperature sensors in TRPV1 activate in two steps to favor opening, and that the binding of sodium to an extracellular site exerts allosteric control over temperature-sensor activation and opening of the pore. The binding of a tarantula toxin to the external pore also exerts control over temperature-sensor activation, whereas binding of vanilloids influences temperature-sensitivity by largely affecting the open/closed equilibrium. Our results reveal a fundamental role of the external pore in the allosteric control of TRPV1 channel gating and provide essential constraints for understanding how these channels can be tuned by diverse stimuli. PMID- 26882505 TI - Long-Term Course of Alternative and Integrative Therapy for Lumbar Disc Herniation and Risk Factors for Surgery: A Prospective Observational 5-Year Follow-Up Study. AB - STUDY DESIGN: Prospective observational 5-year study. OBJECTIVE: To assess pain, functional disability, surgical status, and health care use of patients who actively selected complementary and alternative medicine treatment and risk factors for lumbar surgery. SUMMARY OF BACKGROUND DATA: Controversy continues regarding difference in long-term outcomes of conservative and surgical treatment. METHODS: We recruited 150 consecutive lumbar disc herniation patients with radiating pain (numeric rating scale >=5) from November, 2006 at a Korean medicine hospital outpatient department, of which 128 patients completed 6 months of complementary and alternative medicine treatment (herbal medicine, acupuncture, bee-venom pharmacopuncture, and Chuna manipulation). Follow-up data was collected every year for 5 years. RESULTS: We assessed surgical status in 105 patients (82%), of which 8 replied that they had received surgery. Ninety-two patients (72%) attended the 5-year follow-up. Visual analog scale of back pain which was 4.19 +/- 2.60 at baseline improved after treatment, decreasing to 0.94 +/- 1.13 at 6 months, and was maintained at 1.25 +/- 1.81 at 5 years. Visual analog scale of leg pain decreased from 7.50 +/- 1.32 to 0.94 +/- 1.29 and was sustained at 0.98 +/- 1.73. Participants reported less disability with Oswestry Disability Index scores decreasing from 41.50 +/- 15.07 at baseline to 11.24 +/- 10.44 at 6 months, which then declined further to 7.61 +/- 9.82 at 5 years. SF-36 quality-of-life health survey scores also improved, increasing from 33.41 +/- 12.67 at baseline to 66.04 +/- 15.77 at 6 months, and reaching 75.43 +/- 15.79 at 5 years. In assessment of satisfaction with current state, 20% replied "highly satisfied," 67% "satisfied," 10% "fairly satisfied," and 2% "dissatisfied." Patients with younger age, previous treatment for current pain episode, and higher levels of sensory impairment and pain in the lower extremities were at higher risk of lumbar surgery. CONCLUSION: The long-term results of lumbar disc herniation patients receiving nonsurgical complementary and alternative medicine treatment were favorable and satisfaction rates were high. LEVEL OF EVIDENCE: 2. PMID- 26882506 TI - The Number of Patients and Therapeutic Profile of Spinal Stenosis Using Health Insurance Claims in Japan. AB - STUDY DESIGN: Population-based retrospective descriptive study. OBJECTIVE: To describe the number and therapeutic profile of patients with spinal stenosis at a large-scale community level using health insurance claims data. SUMMARY OF BACKGROUND DATA: A few reports have documented the prevalence of spinal stenosis, and no report has described the therapeutic profile for spinal stenosis in a population base. METHODS: We studied the claims data of National Health Insurance and Late-stage Elderly Health Insurance in a prefecture in Japan from April 2010 to March 2011. We considered patients to have spinal stenosis if their claims included at least one diagnosis coded as spinal stenosis for at least 1 month during the study period. Disease criteria were based on the International Classification of Diseases, 10th version. We then described the number and the therapeutic profile of the patients with spinal stenosis by age and sex. RESULTS: Of 699,723 beneficiaries, 52,889 patients with spinal stenosis were identified. The number of patients with spinal stenosis per 1000 beneficiaries was 76, and those for the subgroups of age >= 65 years, >= 75 years, and >= 85 years were 128, 155, and 152, respectively. The number of patients per 1000 beneficiaries showed unimodal distribution, and the peak for males was 191 between the ages 95 to 99 years and that for females was 160 between the ages 80 to 84 years. Analgesics, prostaglandin E1, or both were prescribed to 40%, 2%, or 20% of patients with spinal stenosis, respectively. Physical therapy, nerve blocks, and surgery were done for 19%, 8%, and 0.4% of the patients, respectively. Approximately, 33% of patients did not receive any treatment. CONCLUSION: There were a large number of patients with spinal stenosis in elderly people. Most of them received nonsurgical treatments. Health insurance claims data could be a useful source of surveillance for such common diseases as spinal stenosis. LEVEL OF EVIDENCE: 4. PMID- 26882507 TI - Diffuse leptomeningeal histiocytic sarcoma in the cerebrospinal fluid of 2 dogs. AB - Two adult male castrated dogs were evaluated for progressive paraparesis and ataxia. Neurologic examination showed severe ataxia, delayed proprioceptive placement in the pelvic limbs, pain upon palpation of the lumbar spine as well as facial paresis in one dog, and decreased withdrawal reflex of the pelvic limbs in the other dog. Magnetic resonance imaging (MRI) in both dogs showed diffuse meningeal and intramedullary lesions. However, no evidence of a mass was found. Biopsies could not be performed safely due to the location of the lesions. Cerebrospinal fluid (CSF) examination revealed an inflammatory pleocytosis associated with increased protein concentration and numerous large atypical round cells, often multinucleated. Nuclear fragmentation, micronuclei, and rare atypical mitoses were observed. Immunocytochemistry revealed CD1(+) and CD11c(+) staining, which, in concert with the morphology confirmed the diagnosis of histiocytic sarcoma (HS). Euthanasia was elected due to poor prognosis. Histopathologic examination showed diffuse spinal and meningeal infiltration with CD18(+) neoplastic cells, without any evidence of mass formation, which completed the diagnosis of diffuse leptomeningeal HS involving the brain and the spinal cord. Canine central nervous system (CNS) HS has been seldom reported in the literature, with only isolated cases identified on CSF cytology. The cases reported here are remarkable in describing a diffuse CNS leptomeningeal HS associated with neoplastic cells in the CSF of dogs without a tumor mass. These cases emphasize the potential critical importance of CSF analysis in providing an antemortem diagnosis of neoplasia in neurologic patients. PMID- 26882508 TI - J-Graft for Correction of Vertical and Horizontal Maxillary Bone Defects. AB - INTRODUCTION: This prospective study aims to evaluate the reliability of a reconstructive technique, which uses autologous J-shaped graft (J-graft) harvested from the mandibular ramus. MATERIALS AND METHODS: Thirty-six maxillary defects among 32 patients (20 women and 12 men) were treated. All patients presented enough bone volume at the donor site to perform the harvesting procedures needed for the autologous reconstruction. All patients underwent clinical and radiographical evaluations through standardized radiographs taken before the intervention, immediately after the bone grafting, 6 to 7 months, and 1 year later. The loss of tooth vitality, the alterations of skin and mucosa sensibility, and the patients' subjective perception of discomfort related to the surgical procedure were investigated. RESULTS: We found an overall success rate of 91.66% with a mean bone gain of 4.8 mm vertically and 5.6 mm horizontally, assessed through computed tomography. According to clinical examinations, 35 sites completely recovered with proper incorporation of the graft, whereas 33 sites reached enough bone volume to allow the implant placement. CONCLUSION: The described technique explains how to harvest and shape a J-graft. It achieves the simultaneous restoration of the horizontal and vertical bone loss with a single bone block. PMID- 26882509 TI - The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia, Lewy body dementia, and Alzheimer's disease: clinical experience in China. AB - BACKGROUND AND AIMS: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. METHOD: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). RESULTS: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. CONCLUSION: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers. PMID- 26882510 TI - Continuity of Care: The Transitional Care Model. AB - Older adults with multiple chronic conditions complicated by other risk factors, such as deficits in activities of daily living or social barriers, experience multiple challenges in managing their healthcare needs, especially during episodes of acute illness. Identifying effective strategies to improve care transitions and outcomes for this population is essential. One rigorously tested model that has consistently demonstrated effectiveness in addressing the needs of this complex population while reducing healthcare costs is the Transitional Care Model (TCM). The TCM is a nurse-led intervention targeting older adults at risk for poor outcomes as they move across healthcare settings and between clinicians. This article provides a detailed summary of the evidence base for the TCM and the model's nine core components. We also discuss measuring the TCM's core components and the overall impact of this evidence-based care management approach. PMID- 26882511 TI - Successes and Challenges in Patient Care Transition Programming: One Hospital's Journey. AB - The 2013 addition of the Care Transition Measures to the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey; enactment of the Patient Protection and Affordable Care Act (2010); and a greater focus on population health have brought a heightened awareness and need for action with patient transitions. Data are emerging from the additional Care Transition Measures and benchmarks have been developed. This article briefly describes the context of care transition. We describe the journey of Indiana University Health North Hospital to overcome patient care transition obstacles, ultimately achieving designation as a top performer. We will discuss our efforts to personalize patient outcomes and transition through activation and improve transitions for vulnerable populations, specifically in the bariatric and orthopedic patient populations. The article concludes with discussion of overcoming obstacles and future directions with continued focus on collaboration and improvement. PMID- 26882512 TI - Pediatric Care Coordination: Lessons Learned and Future Priorities. AB - A fundamental component of the medical home model is care coordination. In Minnesota, this model informed design and implementation of the state's health care home (HCH) model, a key element of statewide healthcare reform legislation. Children with medical complexity (CMC) often require care from multiple specialists and community resources. Coordinating this multi-faceted care within the HCH is challenging. This article describes the need for specialized models of care coordination for CMC. Two models of care coordination for CMC were developed to address this challenge. The TeleFamilies Model of Pediatric Care Coordination uses an advanced practice registered nurse care (APRN) coordinator embedded within an established HCH. The PRoSPer Model of Pediatric Care Coordination uses a registered nurse/social worker care coordinator team embedded within a specialty care system. We describe key findings from implementation of these models, and conclude with lessons learned. Replication of the models is encouraged to increase the evidence base for care coordination for the growing population of children with medical complexities. PMID- 26882513 TI - Registered Nurse Care Coordination: Creating a Preferred Future for Older Adults with Multimorbidity. AB - The concept of care coordination is often touted as the preferred way to streamline care for complex patients. Care coordination is even more popular with the mention of it in the Affordable Care Act of 2010 and with new Medicare payment models. The purpose of this article is to define care coordination, briefly describe trends for older adults and care coordination, and explore roles for registered nurses. We describe elder-appropriate models of care coordination useful for older adults with multimorbidity. A brief exemplar provides an example of evidence-based care coordination services provided by a nursing and social work team, a model supported by recent literature. As a result of this discussion, readers will become informed about possibilities for the future of care delivery and the future of professional nursing practice. PMID- 26882514 TI - Care Transitions in Long-term Care and Acute Care: Health Information Exchange and Readmission Rates. AB - Care transitions between settings are a well-known cause of medical errors. A key component of transition is information exchange, especially in long-term care (LTC). However, LTC is behind other settings in adoption of health information technologies (HIT). In this article, we provide some brief background information about care transitions in LTC and concerns related to technology. We describe a pilot project using HIT and secure messaging in LTC to facilitate electronic information exchange during care transitions. Five LTC facilities were included, all located within Oklahoma and serviced by the same regional health system. The study duration was 20 months. Both inpatient readmission and return emergency department (ED) visit rates were lower than baseline following implementation. We provide discussion of positive outcomes, lessons learned, and limitations. Finally, we offer implications for practice and research for implementation of HIT and information exchange across care settings that may contribute to reduction in readmission rates in acute care and ED settings. PMID- 26882515 TI - Relationships Between Nurses and Physicians Matter. AB - Both safety and quality of care patients receive depend upon the quality of the practice environment where care is provided. In this article, the authors review relevant literature, and describe their study that identified how nurses and physicians define respectful behavior; examined perceptions of the relationship between nurses and physicians in clinical settings in which they practice together; and analyzed the impact of nurse-physician relationships on nursing care decisions. Perceptions of nurse-physician relationships were assessed using the Professional Practice Environment Assessment Scale and perceptions of respectful behavior and the effect of physician behavior on nursing practice were assessed with single, forced-choice items. The authors report finding that physicians rated relationships significantly better than did nurses. Additionally, they note that 55% of nurses said that a physician's behavior impacted nursing decisions, and that younger, less experienced nurses were more likely to report being affected by negative physician behaviors than older nurses or nurses with more experience. They discuss how nurses' and physicians' different perceptions of the same environment is not surprising, but is instructive, and conclude that acknowledging differences in values, incentives, and perceptions can provide insights that focus improvement initiatives. PMID- 26882516 TI - Finding Meaning in the Work of Nursing: An International Study. AB - Sixty nurses from five countries (Canada, India, Ireland, Japan, and Korea) took part in 11 focus groups that discussed the question: Do you consider your work meaningful? Fostering meaning and mentorship as part of the institutional culture was a central theme that emerged from the discussions. In this article, we begin with a background discussion of meaning and meaningful work as presented in the literature related to existentialism and hardiness. Next, we describe the method and analysis processes we used in our qualitative study asking how nurses find meaning in their very challenging work and report our findings of four themes that emerged from the comments shared by nurses, specifically relationships, compassionate caring, identity, and a mentoring culture. After offering a discussion of our findings and noting the limitations of this qualitative study, we conclude that nursing leaders and a culture of mentorship play an important role in fostering meaningful work and developing hardy employees. PMID- 26882518 TI - Ethics: Predatory Publishing: Keeping the Wolves from Your Office Door. PMID- 26882517 TI - Workplace Discrimination: An Additional Stressor for Internationally Educated Nurses. AB - Discrimination against internationally educated nurses (IENs) remains a seldom explored topic in the United States. Yet, the literature describing experiences of IENs indicates that some do experience workplace discrimination as an additional workplace stressor. IENs view this discrimination as an obstacle to career advancement and professional recognition. Consequences of workplace discrimination affect IENs' physical and psychological well being, the quality of patient care, and healthcare organizational costs. In anticipation of future nursing shortages, understanding and minimizing workplace discrimination will benefit nurses, patients, and healthcare organizations. In this article the author addresses motivation and challenges associated with international nurse migration and immigration, relates these challenges to Roy's theoretical framework, describes workplace discrimination, and reviews both consequences of and evidence for workplace discrimination. Next, she considers the significance of this discrimination for healthcare agencies, and approaches for decreasing stress for IENs during their transition process. She concludes that workplace discrimination has a negative, multifaceted effect on both professional nursing and healthcare organizations. Support measures developed to promote mutual respect among all nurses are presented. PMID- 26882519 TI - Legislative: From Policy to Practice: A Case for Holistic Review Diversifying the Nursing Workforce. PMID- 26882520 TI - Cochrane Review Brief: Gloves, Extra Gloves or Special Types of Gloves for Preventing Percutaneous Exposure Injuries in Healthcare Personnel. PMID- 26882521 TI - Cochrane Review Brief: Pharmacotherapies for sleep disturbances in Alzheimer's disease. PMID- 26882522 TI - Cochrane Review Brief: Lifestyle interventions to improve school achievement in overweight or obese children and adolescents. PMID- 26882523 TI - Batch vs continuous-feeding operational mode for the removal of pesticides from agricultural run-off by microalgae systems: A laboratory scale study. AB - Microalgae-based water treatment technologies have been used in recent years to treat different water effluents, but their effectiveness for removing pesticides from agricultural run-off has not yet been addressed. This paper assesses the effect of microalgae in pesticide removal, as well as the influence of different operation strategies (continuous vs batch feeding). The following pesticides were studied: mecoprop, atrazine, simazine, diazinone, alachlor, chlorfenvinphos, lindane, malathion, pentachlorobenzene, chlorpyrifos, endosulfan and clofibric acid (tracer). 2L batch reactors and 5L continuous reactors were spiked to 10 MUg L(-1) of each pesticide. Additionally, three different hydraulic retention times (HRTs) were assessed (2, 4 and 8 days) in the continuous feeding reactors. The batch-feeding experiments demonstrated that the presence of microalgae increased the efficiency of lindane, alachlor and chlorpyrifos by 50%. The continuous feeding reactors had higher removal efficiencies than the batch reactors for pentachlorobenzene, chlorpyrifos and lindane. Whilst longer HRTs increased the technology's effectiveness, a low HRT of 2 days was capable of removing malathion, pentachlorobenzene, chlorpyrifos, and endosulfan by up to 70%. This study suggests that microalgae-based treatment technologies can be an effective alternative for removing pesticides from agricultural run-off. PMID- 26882524 TI - Environmental behavior of engineered nanomaterials in porous media: a review. AB - A pronounced increase in the use of nanotechnology has resulted in nanomaterials being released into the environment. Environmental exposure to the most common engineered nanomaterials (ENMs), such as carbon-based and metal-based nanomaterials, can occur directly via intentional injection for remediation purposes, release during the use of nanomaterial-containing consumer goods, or indirectly via different routes. Recent reviews have outlined potential risks assessments, toxicity, and life cycle analyses regarding ENM emission. In this review, inevitable release of ENMs and their environmental behaviors in aqueous porous media are discussed with an emphasis on influencing factors, including the physicochemical properties of ENMs, solution chemistry, soil hydraulic properties, and soil matrices. Major findings of laboratory column studies and numerical approaches for the transport of ENMs are addressed, and studies on the interaction between ENMs and heavy metal ions in aqueous soil environments are examined. Future research is also presented with specific research directions and outlooks. PMID- 26882525 TI - Attribution of Concussion-Like Symptoms and History of Collision Sports Exposure. PMID- 26882527 TI - The value of urine cytology in the workup of hematuria. PMID- 26882526 TI - Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli. AB - OBJECTIVE: While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ). METHODS: The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme linked immunosorbent assay. RESULTS: We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli. CONCLUSION: The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses. PMID- 26882528 TI - Do Proton Pump Inhibitors Increase the Risk of Dementia? PMID- 26882529 TI - Participation in peer support services and outcomes related to recovery. AB - OBJECTIVE: This article presents findings from a naturalistic study that explored the impact of peer support participation on recovery-related outcomes over a 6 month period. In particular, this study hoped to fill gaps in the literature regarding the process through which personal change occurs in peer support organizations. METHOD: Fifty people newly involved in services provided by Baltic Street AEH (Advocacy, Employment, Housing), a consumer-operated organization, participated in the study. Participants were interviewed at entry and 3- and 6 month follow-up. Attendance records were reviewed to determine the number of days attended, and the sample was divided into 2 categories: minimal or nonattenders (n = 25) and moderate or high attenders (n = 21). The relationship between attendance and outcomes related to recovery over time was examined using a mixed effect regression analysis, allowing data to be included for participants with at least 1 follow-up interview (n = 38). RESULTS: Relative to minimal or nonattenders, moderate or high attenders showed statistically significant improvements over time in internalized stigma, self-esteem-self-efficacy, and community activism-autonomy. No statistically significant differences were observed between groups in hopelessness, social functioning, symptom severity, coping with symptoms, or substance use. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: This study demonstrates the potential impact of engagement in peer support services on some subjective aspects of mental health recovery. Namely, change mechanisms could be hypothesized to include identity transformation (from patient to peer). Future directions should continue to investigate potential mechanisms of change with larger samples in randomized studies. (PsycINFO Database Record PMID- 26882532 TI - The global burden of oral diseases in pediatric HIV-infected populations: a workshop report. AB - OBJECTIVES: To achieve a comprehensive understanding about the global burden of oral diseases in HIV-infected children and to identify research needs. MATERIALS AND METHODS: A literature search was conducted in PubMed (2009-2014) to address five questions: (i) prevalence of oral diseases in HIV-infected compared with uninfected children, (ii) impact of oral diseases on quality of life, (iii) effect of antiretroviral exposure in utero on craniofacial and dental development, (iv) important co-infections and antiretroviral complications, and (v) value of atraumatic restorative treatment. RESULTS: Studies showed a high prevalence of dental caries in HIV-infected children but the relationship between HIV infection and dental caries remains unclear. Also quality of life needs further investigation supported by better study designs and improvement of the instruments used. Up-to-date evidence suggested long-term harms associated with in utero antiretroviral exposure were minor but would require long-term follow-up through National Registries. The reviews also revealed the wide spectrum of metabolic disease due to antiretroviral therapy and co-infections such as tuberculosis. Finally, atraumatic restorative technique appears to be a simple and safe technique to treat dental caries but outcomes need further evaluation. CONCLUSIONS: The impact of antiretroviral therapy in HIV-infected children has raised novel challenging questions in the field of oral health warranting future research. PMID- 26882530 TI - Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon Dioxide. AB - PURPOSE: The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina. METHODS: Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model. RESULTS: Loading efficiency of Dex was 69 +/- 9 MUg per 1 mg of the pSiO2 COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO Dex particles (mean 2.71 +/- 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study. CONCLUSIONS: The porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction. PMID- 26882533 TI - Effects of active/passive interventions on pain, anxiety, and quality of life in women with fibromyalgia: Randomized controlled pilot trial. AB - The authors of this study compared the effects of pilates exercises and connective tissue massage (CTM) on pain intensity; pain-pressure threshold; and tolerance, anxiety, progress, and health-related quality of life in females with fibromyalgia. It was a pilot, assessor masked, randomized controlled trial conducted between January and August of 2013. Twenty-one women with fibromyalgia were randomly assigned to the pilates exercise program (six of whom did not complete the program), and 22 were randomly assigned to CTM (one of whom did not complete this program). Each group received the assigned intervention three times per week during a 4-week period. The Visual Analogue Scale, algometry, State Trait Anxiety Inventory, Fibromyalgia Impact Questionnaire, and Nottingham Health Profile were used at baseline and at the end of treatments. Significant improvements were found in both groups for all parameters. However, the scores for pain-pressure threshold were significantly elevated and the symptoms of anxiety were significantly diminished in the exercise group compared to the massage group. Thus, exercise and massage might be used to provide improvements in women with fibromyalgia. The exercise group showed more advantages than the massage group and thus might be preferred for patients with fibromyalgia. However, an adequately powered trial is required to determine this with certainty. PMID- 26882534 TI - The Patient-Centered Medical Home and Associations With Health Care Quality and Utilization: A 5-Year Cohort Study. AB - BACKGROUND: Effects of the patient-centered medical home (PCMH) are unclear. Previous studies had relatively short follow-up and may not have distinguished effects of the PCMH (which involves electronic health records [EHRs] plus organizational changes) from those of EHRs alone. OBJECTIVE: To determine effects of the PCMH on health care quality and utilization compared with paper records alone and EHRs alone, with extended follow-up. DESIGN: Prospective cohort study (2008 to 2012), including 3 years after PCMH implementation. (ClinicalTrials.gov: NCT00793065). SETTING: The Hudson Valley, a multipayer, multiprovider region in New York. PARTICIPANTS: 438 primary care physicians in 226 practices, with 136 480 patients across 5 health plans. INTERVENTION: Level III PCMH, as defined by the National Committee for Quality Assurance. MEASUREMENTS: Claims-based outcomes included 8 quality and 7 utilization measures. Generalized estimating equations were used to compare adjusted differences in rates of change across study groups. RESULTS: Patterns of quality were fairly similar across groups. Utilization patterns were similar across groups from 2008 to 2011 but showed modest differences between the PCMH and control groups on most measures in 2012. For example, hospitalizations were relatively stable from 2008 to 2011 (approximately 3.9 to 5.2 per 100 patients per year) but decreased in the PCMH group in 2012 (incidence rate ratio, 0.79 [95% CI, 0.69 to 0.90] compared with paper records). Emergency department visits were highest for the PCMH group (16.7 per 100 patients at baseline and 15.4 per 100 patients at the end of the study period) and lowest for the paper group (14.3 per 100 patients at baseline and 12.2 per 100 patients at the end of the study period), but the rate of change did not differ across groups. LIMITATION: Possible unmeasured confounding. CONCLUSION: The PCMH was associated with modest changes in most utilization measures and provided similar quality compared with EHRs and paper records. PRIMARY FUNDING SOURCE: The Commonwealth Fund and the New York State Department of Health. PMID- 26882535 TI - Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region. AB - The increasing human presence in Antarctica and the waste it generates is causing an impact on the environment at local and border scale. The main sources of anthropic pollution have a mainly local effect, and include the burning of fossil fuels, waste incineration, accidental spillage and wastewater effluents, even when treated. The aim of this work is to determine the presence and origin of 30 substances of anthropogenic origin considered to be, or suspected of being, endocrine disruptors in the continental waters of the Antarctic Peninsula region. We also studied a group of toxic metals, metalloids and other elements with possible endocrine activity. Ten water samples were analyzed from a wide range of sources, including streams, ponds, glacier drain, and an urban wastewater discharge into the sea. Surprisingly, the concentrations detected are generally similar to those found in other studies on continental waters in other parts of the world. The highest concentrations of micropollutants found correspond to the group of organophosphate flame retardants (19.60-9209ngL(-1)) and alkylphenols (1.14-7225ngL(-1)); and among toxic elements the presence of aluminum (a possible hormonal modifier) (1.7-127ugL(-1)) is significant. The concentrations detected are very low and insufficient to cause acute or subacute toxicity in aquatic organisms. However, little is known as yet of the potential sublethal and chronic effects of this type of pollutants and their capacity for bioaccumulation. These results point to the need for an ongoing system of environmental monitoring of these substances in Antarctic continental waters, and the advisability of regulating at least the most environmentally hazardous of these in the Antarctic legislation. PMID- 26882536 TI - Phe362Tyr in AChE: A Major Factor Responsible for Azamethiphos Resistance in Lepeophtheirus salmonis in Norway. AB - Organophosphates (OP) are one of the major treatments used against the salmon louse (Lepeophtherius salmonis) in Norwegian salmonid aquaculture. The use of OP since the late 1970s has resulted in widespread resistant parasites. Recently, we reported a single mutation (Phe362Tyr) in acetylcholinesterase (AChE) as the major mechanism behind resistance in salmon louse towards OP. The present study was carried out to validate this mechanism at the field level. A total of 6658 salmon louse samples were enrolled from 56 different fish farms across the Norwegian coast, from Vest Agder in the south to Finnmark in the north. All the samples were genotyped using a TaqMan probe assay for the Phe362Tyr mutation. A strong association was observed between areas with frequent use of the OP (azamethiphos) and the Phe362Tyr mutation. This was confirmed at 15 sites where results from independently conducted bioassays and genotyping of parasites correlated well. Furthermore, genotyping of surviving and moribund parasites from six bioassay experiments demonstrated a highly significant negative correlation between the frequency of resistance alleles and the probability of dying when exposed to azamethiphos in a bioassay. Based on these observations, we could strongly conclude that the Phe362Tyr mutation is a major factor responsible for OP resistance in salmon louse on Norwegian fish farms. PMID- 26882537 TI - Breast Cancer Survivors' Supportive Care Needs, Posttraumatic Growth and Satisfaction with Doctors' Interpersonal Skills in Relation to Physical Activity 8 Months after the End of Treatment: A Prospective Exploratory Study. AB - OBJECTIVE: We assessed whether breast cancer survivors' (BCSs) supportive care needs, posttraumatic growth (positive psychological changes) and satisfaction with doctors' interpersonal skills could be related to physical activity (PA). METHODS: A total of 426 BCSs were approached during the last week of treatment. Eight months later, 278 (65%) provided information on their PA levels. Ordinal logistic multiple regressions were performed. RESULTS: PA levels included no PA (n = 68), some PA (n = 83), high PA levels more than twice or more than 2 h per week (n = 127). The multivariate model significantly explained 13% of PA variance (p = 0.001). An increase in posttraumatic growth total scores (proportional OR = 1.310; p < 0.05) and a decrease in physical and daily living supportive care needs subscale scores (proportional OR = 0.980; p < 0.001) and in satisfaction with doctors' interpersonal skill scores (proportional OR = 0.898; p < 0.05) were significantly associated with an increase in the likelihood of performing higher levels of PA. A lower educational level was associated with a decrease in the likelihood of performing PA. CONCLUSION: The prevalence of PA in BCSs should be improved. Positive psychological changes after a breast cancer experience might contribute to performing PA. Encouraging PA needs to be accompanied by the alleviation of physical symptoms. PMID- 26882538 TI - Endoluminal loco-regional resection by TEM after R1 endoscopic removal or recurrence of rectal tumors. AB - PURPOSE: The aim of this study is to evaluate the safety and efficacy of endoluminal loco-regional resection (ELRR) by transanal endoscopic microsurgery (TEM) after R1 endoscopic resection or local recurrence of early rectal cancer after operative endoscopy. MATERIAL AND METHODS: Twenty patients with early rectal cancer were enrolled, including patients with incomplete endoscopic resection, or complete endoscopic resection of a tumor with unfavorable prognostic factors (group A, ten patients), and local recurrence after endoscopic removal (group B, ten patients). At admission, histology after endoscopic polypectomy was: TisR1(4), T1R0G3(1), T1R1(5) in group A, and TisR0(8), T1R0(2) in group B. All patients underwent ELRR by TEM with nucleotide-guided mesorectal excision (NGME). RESULTS: Mean operative time was 150 minutes. Complications occurred in two patients (10%). Definitive histology was: moderate dysplasia(4), pT0N0(3), pTisN0(5), pT1N0(6), pT2N0(2). Mean number of lymph-nodes was 3.1. Mean follow-up was 79.5 months. All patients are alive and disease-free. CONCLUSIONS: ELRR by TEM after R1 endoscopic resection of early rectal cancer or for local recurrence after operative endoscopy is safe and effective. It may be considered as a diagnostic procedure, as well as a curative treatment option, instead of a more invasive TME. PMID- 26882539 TI - An open access pilot freely sharing cancer genomic data from participants in Texas. AB - Genomic data sharing in cancer has been restricted to aggregate or controlled access initiatives to protect the privacy of research participants. By limiting access to these data, it has been argued that the autonomy of individuals who decide to participate in data sharing efforts has been superseded and the utility of the data as research and educational tools reduced. In a pilot Open Access (OA) project from the CPRIT-funded Texas Cancer Research Biobank, many Texas cancer patients were willing to openly share genomic data from tumor and normal matched pair specimens. For the first time, genetic data from 7 human cancer cases with matched normal are freely available without requirement for data use agreements nor any major restriction except that end users cannot attempt to re identify the participants (http://txcrb.org/open.html). PMID- 26882540 TI - Hand, Foot, and Mouth Disease in China: Modeling Epidemic Dynamics of Enterovirus Serotypes and Implications for Vaccination. AB - BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co circulation, and implications for vaccination, of additional non-EV-A71, non-CV A16 serotypes of enterovirus. METHODS AND FINDINGS: Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible-infected-recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71 vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16. CONCLUSIONS: The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden. PMID- 26882541 TI - Attribution of Concussion-Like Symptoms and History of Collision Sports Exposure- Reply. PMID- 26882542 TI - Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts. AB - IMPORTANCE: Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear. OBJECTIVE: To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26,184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years. EXPOSURES: Consumption of fish during pregnancy. MAIN OUTCOMES AND MEASURES: We estimated offspring body mass index percentile trajectories from 3 months after birth to 6 years of age. We defined rapid infant growth as a weight gain z score greater than 0.67 from birth to 2 years and childhood overweight/obesity at 4 and 6 years as body mass index in the 85th percentile or higher for age and sex. We calculated cohort-specific effect estimates and combined them by random-effects meta-analysis. RESULTS: This multicenter, population-based birth cohort study included the 26,184 pregnant women and their children. The median fish intake during pregnancy ranged from 0.5 times/week in Belgium to 4.45 times/week in Spain. Women who ate fish more than 3 times/week during pregnancy gave birth to offspring with higher body mass index values from infancy through middle childhood compared with women with lower fish intake (3 times/week or less). High fish intake during pregnancy (>3 times/week) was associated with increased risk of rapid infant growth, with an adjusted odds ratio (aOR) of 1.22 (95% CI, 1.05-1.42) and increased risk of offspring overweight/obesity at 4 years (aOR, 1.14 [95% CI, 0.99-1.32]) and 6 years (aOR, 1.22 [95% CI, 1.01-1.47]) compared with an intake of once per week or less. Interaction analysis showed that the effect of high fish intake during pregnancy on rapid infant growth was greater among girls (aOR, 1.31 [95% CI, 1.08-1.59]) than among boys (aOR, 1.11 [95% CI, 0.92-1.34]; P = .02 for interaction). CONCLUSIONS AND RELEVANCE: High maternal fish intake during pregnancy was associated with increased risk of rapid growth in infancy and childhood obesity. Our findings are in line with the fish intake limit proposed by the US Food and Drug Administration and Environmental Protection Agency. PMID- 26882543 TI - NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. AB - As a genome guardian, p53 maintains genome stability by arresting cells for damage repair or inducing cell apoptosis to eliminate the damaged cells in stress response. Several nucleolar proteins stabilize p53 by interfering Mdm2-p53 interaction upon cellular stress, while other mechanisms by which nucleolar proteins activate p53 remain to be determined. Here, we identify NAT10 as a novel regulator for p53 activation. NAT10 acetylates p53 at K120 and stabilizes p53 by counteracting Mdm2 action. In addition, NAT10 promotes Mdm2 degradation with its intrinsic E3 ligase activity. After DNA damage, NAT10 translocates to nucleoplasm and activates p53-mediated cell cycle control and apoptosis. Finally, NAT10 inhibits cell proliferation and expression of NAT10 decreases in human colorectal carcinomas. Thus, our data demonstrate that NAT10 plays a critical role in p53 activation via acetylating p53 and counteracting Mdm2 action, providing a novel pathway by which nucleolar protein activates p53 as a cellular stress sensor. PMID- 26882544 TI - Response to interferons and antibacterial innate immunity in the absence of tyrosine-phosphorylated STAT1. AB - Signal transducer and activator of transcription 1 (STAT1) plays a pivotal role in the innate immune system by directing the transcriptional response to interferons (IFNs). STAT1 is activated by Janus kinase (JAK)-mediated phosphorylation of Y701. To determine whether STAT1 contributes to cellular responses without this phosphorylation event, we generated mice with Y701 mutated to a phenylalanine (Stat1(Y701F)). We show that heterozygous mice do not exhibit a dominant-negative phenotype. Homozygous Stat1(Y701F) mice show a profound reduction in Stat1 expression, highlighting an important role for basal IFN dependent signaling. The rapid transcriptional response to type I IFN (IFN-I) and type II IFN (IFNgamma) was absent in Stat1(Y701F) cells. Intriguingly, STAT1Y701F suppresses the delayed expression of IFN-I-stimulated genes (ISG) observed in Stat1(-/-) cells, mediated by the STAT2/IRF9 complex. Thus, Stat1(Y701F) macrophages are more susceptible to Legionella pneumophila infection than Stat1( /-) macrophages. Listeria monocytogenes grew less robustly in Stat1(Y701F) macrophages and mice compared to Stat1(-/-) counterparts, but STAT1Y701F is not sufficient to rescue the animals. Our studies are consistent with a potential contribution of Y701-unphosphorylated STAT1 to innate antibacterial immunity. PMID- 26882545 TI - Lack of TRPV2 impairs thermogenesis in mouse brown adipose tissue. AB - Brown adipose tissue (BAT), a major site for mammalian non-shivering thermogenesis, could be a target for prevention and treatment of human obesity. Transient receptor potential vanilloid 2 (TRPV2), a Ca(2+)-permeable non selective cation channel, plays vital roles in the regulation of various cellular functions. Here, we show that TRPV2 is expressed in brown adipocytes and that mRNA levels of thermogenic genes are reduced in both cultured brown adipocytes and BAT from TRPV2 knockout (TRPV2KO) mice. The induction of thermogenic genes in response to beta-adrenergic receptor stimulation is also decreased in TRPV2KO brown adipocytes and suppressed by reduced intracellular Ca(2+) concentrations in wild-type brown adipocytes. In addition, TRPV2KO mice have more white adipose tissue and larger brown adipocytes and show cold intolerance, and lower BAT temperature increases in response to beta-adrenergic receptor stimulation. Furthermore, TRPV2KO mice have increased body weight and fat upon high-fat-diet treatment. Based on these findings, we conclude that TRPV2 has a role in BAT thermogenesis and could be a target for human obesity therapy. PMID- 26882546 TI - GemC1 controls multiciliogenesis in the airway epithelium. AB - Multiciliated cells are terminally differentiated, post-mitotic cells that form hundreds of motile cilia on their apical surface. Defects in multiciliated cells lead to disease, including mucociliary clearance disorders that result from ciliated cell disfunction in airways. The pathway controlling multiciliogenesis, however, remains poorly characterized. We showed that GemC1, previously implicated in cell cycle control, is a central regulator of ciliogenesis. GemC1 is specifically expressed in ciliated epithelia. Ectopic expression of GemC1 is sufficient to induce early steps of multiciliogenesis in airway epithelial cells ex vivo, upregulating McIdas and FoxJ1, key transcriptional regulators of multiciliogenesis. GemC1 directly transactivates the McIdas and FoxJ1 upstream regulatory sequences, and its activity is enhanced by E2F5 and inhibited by Geminin. GemC1-knockout mice are born with airway epithelia devoid of multiciliated cells. Our results identify GemC1 as an essential regulator of ciliogenesis in the airway epithelium and a candidate gene for mucociliary disorders. PMID- 26882547 TI - miR-515-5p controls cancer cell migration through MARK4 regulation. AB - Here, we show that miR-515-5p inhibits cancer cell migration and metastasis. RNA seq analyses of both oestrogen receptor receptor-positive and receptor-negative breast cancer cells overexpressing miR-515-5p reveal down-regulation of NRAS, FZD4, CDC42BPA, PIK3C2B and MARK4 mRNAs. We demonstrate that miR-515-5p inhibits MARK4 directly 3' UTR interaction and that MARK4 knock-down mimics the effect of miR-515-5p on breast and lung cancer cell migration. MARK4 overexpression rescues the inhibitory effects of miR-515-5p, suggesting miR-515-5p mediates this process through MARK4 down-regulation. Furthermore, miR-515-5p expression is reduced in metastases compared to primary tumours derived from both in vivo xenografts and samples from patients with breast cancer. Conversely, miR-515-5p overexpression prevents tumour cell dissemination in a mouse metastatic model. Moreover, high miR-515-5p and low MARK4 expression correlate with increased breast and lung cancer patients' survival, respectively. Taken together, these data demonstrate the importance of miR-515-5p/MARK4 regulation in cell migration and metastasis across two common cancers. PMID- 26882548 TI - Feedback regulation between atypical E2Fs and APC/CCdh1 coordinates cell cycle progression. AB - E2F transcription factors control the oscillating expression pattern of multiple target genes during the cell cycle. Activator E2Fs, E2F1-3, induce an upswing of E2F targets, which is essential for the G1-to-S phase transition, whereas atypical E2Fs, E2F7 and E2F8, mediate a downswing of the same targets during late S, G2, and M phases. Expression of atypical E2Fs is induced by E2F1-3, but it is unknown how atypical E2Fs are inactivated in a timely manner. Here, we demonstrate that E2F7 and E2F8 are substrates of the anaphase-promoting complex/cyclosome (APC/C). Removal of CDH1, or mutating the CDH1-interacting KEN boxes, stabilized E2F7/8 from anaphase onwards and during G1. Expressing KEN mutant E2F7 during G1 impairs S phase entry and eventually results in cell death. Furthermore, we show that E2F8, but not E2F7, interacts also with APC/C(C) (dc20). Importantly, atypical E2Fs can activate APC/C(C) (dh1) by repressing its inhibitors cyclin A, cyclin E, and Emi1. In conclusion, we discovered a feedback loop between atypical E2Fs and APC/C(C) (dh1), which ensures balanced expression of cell cycle genes and normal cell cycle progression. PMID- 26882549 TI - Exploiting dominant-negative toxins to combat Staphylococcus aureus pathogenesis. AB - Staphylococcus aureus (S. aureus) is a human pathogen that relies on the subversion of host phagocytes to support its pathogenic lifestyle. S. aureus strains can produce up to five beta-barrel, bi-component, pore-forming leukocidins that target and kill host phagocytes. Thus, preventing immune cell killing by these toxins is likely to boost host immunity. Here, we describe the identification of glycine-rich motifs within the membrane-penetrating stem domains of the leukocidin subunits that are critical for killing primary human neutrophils. Remarkably, leukocidins lacking these glycine-rich motifs exhibit dominant-negative inhibitory effects toward their wild-type toxin counterparts as well as other leukocidins. Biochemical and cellular assays revealed that these dominant-negative toxins work by forming mixed complexes that are impaired in pore formation. The dominant-negative leukocidins inhibited S. aureus cytotoxicity toward primary human neutrophils, protected mice from lethal challenge by wild-type leukocidin, and reduced bacterial burden in a murine model of bloodstream infection. Thus, we describe the first example of staphylococcal bi-component dominant-negative toxins and their potential as novel therapeutics to combat S. aureus infection. PMID- 26882550 TI - Chromosome misalignments induce spindle-positioning defects. AB - Cortical pulling forces on astral microtubules are essential to position the spindle. These forces are generated by cortical dynein, a minus-end directed motor. Previously, another dynein regulator termed Spindly was proposed to regulate dynein-dependent spindle positioning. However, the mechanism of how Spindly regulates spindle positioning has remained elusive. Here, we find that the misalignment of chromosomes caused by Spindly depletion is directly provoking spindle misorientation. Chromosome misalignments induced by CLIP-170 or CENP-E depletion or by noscapine treatment are similarly accompanied by severe spindle positioning defects. We find that cortical LGN is actively displaced from the cortex when misaligned chromosomes are in close proximity. Preventing the KT recruitment of Plk1 by the depletion of PBIP1 rescues cortical LGN enrichment near misaligned chromosomes and re-establishes proper spindle orientation. Hence, KT-enriched Plk1 is responsible for the negative regulation of cortical LGN localization. In summary, we uncovered a compelling molecular link between chromosome alignment and spindle orientation defects, both of which are implicated in tumorigenesis. PMID- 26882552 TI - No time to waste on the road to a liberal eugenics? PMID- 26882553 TI - "I bet you won't": The science-society wager on gene editing techniques. PMID- 26882554 TI - Carl Woese's worries about the role of bio-engineering. PMID- 26882551 TI - The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. AB - The quality of mitochondria, essential organelles that produce ATP and regulate numerous metabolic pathways, must be strictly monitored to maintain cell homeostasis. The loss of mitochondrial quality control systems is acknowledged as a determinant for many types of neurodegenerative diseases including Parkinson's disease (PD). The two gene products mutated in the autosomal recessive forms of familial early-onset PD, Parkin and PINK1, have been identified as essential proteins in the clearance of damaged mitochondria via an autophagic pathway termed mitophagy. Recently, significant progress has been made in understanding how the mitochondrial serine/threonine kinase PINK1 and the E3 ligase Parkin work together through a novel stepwise cascade to identify and eliminate damaged mitochondria, a process that relies on the orchestrated crosstalk between ubiquitin/phosphorylation signaling and autophagy. In this review, we highlight our current understanding of the detailed molecular mechanisms governing Parkin /PINK1-mediated mitophagy and the evidences connecting Parkin/PINK1 function and mitochondrial clearance in neurons. PMID- 26882555 TI - A new approach to toxin neutralization in Staphylococcus aureus therapy. PMID- 26882556 TI - Response by Caplan et al. PMID- 26882557 TI - Social influence and peer review - impact factor and citation. PMID- 26882558 TI - Sophisticated sleep improves our brains: Our advanced cognitive and social skills might derive from the evolution of improved sleep quality; today, sleep therapy could help with mental health issues and learning. PMID- 26882559 TI - Chilling without regrets: Deciphering the effects of cryopreservation on the epigenetic properties of frozen cells will benefit the applications of cryo technology. PMID- 26882560 TI - The translational relevance of Drosophila in drug discovery. PMID- 26882561 TI - Tree Based Method for Aggregate Survival Data Modeling. AB - In many scenarios, a patient in medical research is treated as a statistical unit. However, in some scenarios, we are interested in treating aggregate data as a statistical unit. In such situations, each set of aggregated data is considered to be a concept in a symbolic representation, and each concept has a hyperrectangle or multiple points in the variable space. To construct a tree structured model from these aggregate survival data, we propose a new approach, where a datum can be included in several terminal nodes in a tree. By constructing a model under this condition, we expect to obtain a more flexible model while retaining the interpretive ease of a hierarchical structure. In this approach, the survival function of concepts that are partially included in a node is constructed using the Kaplan-Meier method, where the number of events and risks at each time point is replaced by the expectation value of the number of individual descriptions of concepts. We present an application of this proposed model using primary brain tumor patient data. As a result, we obtained a new interpretation of the data in comparison to the classical survival tree modeling methods. PMID- 26882562 TI - microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer. AB - Head and neck squamous cell carcinoma (HNSCC) has a high capacity for invasion. To identify microRNAs (miRNAs) that regulate HNSCC invasion, we compared miRNA expression profiles between a parent HNSCC cell line and a highly invasive clone. The miR-200 family and miR-203 were downregulated in the clone. Here we focused on the role of miR-203 in invasion and epithelial-mesenchymal transition (EMT) induction in HNSCC. miR-203 was downregulated during EMT induction. Moreover, ectopic overexpression of miR-203 suppressed the invasion and induced mesenchymal epithelial transition (MET) in HNSCC cells. Interestingly, we identified NUAK family SNF1-like kinase 1 (NUAK1) as a novel target gene of miR-203 by cyclopedic analysis using anti-Ago2 antibody. Increased expression of NUAK1 was observed during EMT induction, and ectopic expression of miR-203 delayed EMT induction by suppressing NUAK1 expression. Moreover, NUAK1 overexpression promoted the invasion of HNSCC cells. Importantly, NUAK1 expression was well correlated with poor differentiation, invasiveness, and lymph node metastasis in HNSCC cases. Overall, miR-203 has a tumor-suppressing role in invasion and EMT induction by targeting NUAK1 in HNSCC, suggesting miR-203 as a potential new diagnostic and therapeutic target for the treatment of HNSCC. PMID- 26882563 TI - CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR 425. AB - Hepatocellular carcinoma (HCC) is a common and leading cause of death worldwide. Here, we identified that a cell-cell adhesion gene, CTNNA3, is a tumor suppressor in HCC. CTNNA3 inhibited the proliferation, migration and invasion of HCC cell lines. In these cells, CTNNA3 inhibited Akt signal, and in turn decreased the proliferating cell nuclear antigen (PCNA) and the matrix metallopeptidase MMP-9, and increased the cell cycle inhibitor p21(Cip1/Waf1). Meanwhile, CTNNA3 is inhibited by miR-425 in HCC. The miR-425 directly bound to the 3'UTR of CTNNA3 and inhibited its expression. The tumor suppressor function of CTNNA3 and the oncogenic function of miR-425 were further confirmed in HCC cell xenograft in nude mice. The miR-425/CTNNA3 axis may provide insights into the mechanisms underlying HCC, and contribute to potential therapeutic strategy of HCC. PMID- 26882564 TI - microRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia. AB - The transcription factor TAL1 is a proto-oncogene whose aberrant expression in committed T-cell precursors is associated with the development of T-cell acute lymphoblastic leukemia (T-ALL). The mechanisms leading to aberrant activation of TAL1 in T-ALL patients who lack chromosomal rearrangements involving the TAL1 locus remain largely unknown. We hypothesized that TAL1 levels decrease during normal T-cell development at least in part due to miRNA-dependent silencing, in which case TAL1 over-expression in some T-ALL cases could be the consequence of deregulated miRNA expression. By performing computational prediction of miRNAs that bind to the human TAL1 mRNA we compiled a list of miRNAs that are candidates to regulate TAL1. Using a luciferase reporter system and mutagenesis assays we confirmed the miRNA-TAL1 mRNA interactions and selected candidate miRNAs: miR 101, miR-520d-5p, miR-140-5p, miR-448 and miR-485-5p. Over-expression of these microRNAs in different T-ALL cell lines consistently resulted in the down regulation of TAL1 protein. In accordance, inhibition of miR-101 and miR-520d-5p promoted TAL1 protein expression. Importantly, we found that miR-101, miR-140-5p, miR-448 and miR-485-5p were down-regulated in T-ALL patient specimens and T-ALL cell lines. Our results show for the first time the existence of epigenetic regulation of TAL1 by specific miRNAs which may contribute, at least in part, to the ectopic expression of TAL1 in some T-ALL cases. PMID- 26882565 TI - Identification of an aptamer through whole cell-SELEX for targeting high metastatic liver cancers. AB - Hepatocellular carcinoma (HCC) is one of the most deadly human cancers due to its ability of invasion and metastasis. Thus, the approaches to identify potential compounds that inhibit invasion and metastasis of HCC are critical for treatment of this disease. In the present study, we used HCCLM9 cells with high metastatic potential and MHCC97L with low metastatic potential as a model system to study the molecular mechanisms of HCC metastasis. By applying cell- Systematic Evolution of Ligands by Exponential enrichment (SELEX) against living cells, we used HCCLM9 as target cells and MHCC97L cells as control to screen a group of HCC metastasis- and cell-specific DNA aptamers. One of selected aptamers, LY-1, could specifically bind to metastatic HCC with a dissociation constant (Kd) in nanomolar range. In vitro studies demonstrated that LY-1 can recognize and bind to membrane protein of metastatic HCC cells. Furthermore, QD605 labeled LY-1 aptamer could recognize HCC cells in both local liver cancer tissues and pulmonary metastatic sites in a xenograft model of HCC with pulmonary metastasis. Further biochemical and immunostaining studies showed that LY-1 could selectively bind to a subpopulation of more metastatic cells in HCCLM9 cells, which express more CK19 and vimentin. Finally, treatment of highly metastatic cells with LY-1 led to reduced migration and invasiveness of HCCLM9 cells in vitro and suppression of xenograft growth in vivo. Taken together, the present study demonstrated the tumor targeting and tumor suppressive effects of LY-1, which could be a promising molecular probe for metastatic HCC and a potential candidate of chemotherapy for metastatic HCC. PMID- 26882566 TI - A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells. AB - CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC 73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression. PMID- 26882567 TI - Identification of approved and investigational drugs that inhibit hypoxia inducible factor-1 signaling. AB - One of the requirements for tumor development is blood supply, most often driven by hypoxia-induced angiogenesis. Hypoxia induces the stabilization of hypoxia inducible factor-1 alpha (HIF-1alpha), which induces expression of an angiogenic factor, vascular endothelial growth factor (VEGF). The purpose of this study is to validate a new screening platform combined with orthogonal assays to rapidly identify HIF-1 inhibitors and to evaluate the effectiveness of approved drugs on modulating HIF-1 signaling. We generated an endogenous HIF-1alpha-NanoLuc luciferase reporter allele in the human HCT116 colon cancer cell line using genome editing and screened a panel of small interfering RNAs (siRNAs) to 960 druggable targets and approximately 2,500 drugs on a quantitative high-throughput screening (qHTS) platform. Selected compounds were further investigated with secondary assays to confirm their anti-HIF activity and to study their mode of action. The qHTS assay identified over 300 drugs that inhibited HIF-1alpha NanoLuc expression. The siRNA screening results supported the effectiveness of several target-specific inhibitors. Moreover, the identified HIF-1 inhibitors, such as mycophenolate mofetil, niclosamide, and trametinib, were able to suppress cancer cell proliferation and angiogenesis. Our study indicates that blocking the mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways effectively inhibits hypoxia-induced HIF-1alpha accumulation and HIF 1alpha transactivation and that proteasome inhibitors induce accumulation and decrease transcriptional activity of HIF-1alpha. These findings underline the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies. PMID- 26882568 TI - LOX expression in primary nasopharyngeal carcinoma: correlation with prognostic parameters and outcome. AB - Lysyl oxidase (LOX) is an extracellular matrix-remodeling enzyme that plays important roles in tumor development and progression. To evaluate the prognostic value of LOX levels in primary nasopharyngeal carcinoma, we performed an immunohistochemical analysis using 233 tissue biopsy specimens from as many patients. We found that the extent of immunohistochemical LOX staining correlated inversely with the clinicopathological features and survival. High LOX expression correlated with decreases in 5-year survival, overall survival, distant metastasis-free survival and disease-free survival (p < 0.05). Cox regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 1.670; 95% confidence interval [95% CI], 1.033-2.701 [p < .005]). Higher LOX expression was also an independent predictor of poor prognosis in patients with nasopharyngeal carcinoma. These findings suggest LOX may be a new biomarker predictive of NPC prognosis and may also be a useful treatment target. PMID- 26882570 TI - Talking about domestic abuse: Crucial conversations for health visitors. AB - Domestic abuse is a serious problem across the world and it is considered a public health issue. Nurses play a crucial role in recognising and responding to domestic abuse but they sometimes lack confidence in dealing with the issue. In this article, two recently completed studies are used to extract lessons for health visiting practice. The first study investigated primary healthcare professionals' beliefs about domestic abuse. Many healthcare professionals were confident in dealing with domestic abuse. However, there was disinclination among some to discuss the issue. People who experience abuse rarely discuss it unless asked. So the study highlighted a potential dynamic of silence between health professionals and abused people in their care. The second study investigated student nurses and student midwives experiences of learning about domestic abuse. The student nurses had learned less than the student midwives. They had not been taught about domestic abuse in university and many had not had the opportunity to learn about it in clinical placement. They reported reluctance among some mentors to discuss the issue with them, with a resulting silencing of the issue. Both of these studies have important lessons for health visiting practice regarding opening up crucial conversations about domestic abuse. PMID- 26882569 TI - A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers. AB - mTOR inhibition has emerged as a promising strategy for head and neck squamous cell carcinomas (HNSCC) treatment. However, most targeted therapies ultimately develop resistance due to the activation of adaptive survival signaling mechanisms limiting the activity of targeted agents. Thus, co-targeting key adaptive mechanisms may enable more effective cancer cell killing. Here, we performed a synthetic lethality screen using shRNA libraries to identify druggable candidates for combinatorial signal inhibition. We found that the ERK pathway was the most highly represented. Combination of rapamycin with trametinib, a MEK1/2 inhibitor, demonstrated strong synergism in HNSCC-derived cells in vitro and in vivo, including HNSCC cells expressing the HRAS and PIK3CA oncogenes. Interestingly, cleaved caspase-3 was potently induced by the combination therapy in PIK3CA+ cells in vitro and tumor xenografts. Moreover, ectopic expression of PIK3CA mutations into PIK3CA- HNSCC cells sensitized them to the pro-apoptotic activity of the combination therapy. These findings indicate that co-targeting the mTOR/ERK pathways may provide a suitable precision strategy for HNSCC treatment. Moreover, PIK3CA+ HNSCC are particularly prone to undergo apoptosis after mTOR and ERK inhibition, thereby providing a potential biomarker of predictive value for the selection of patients that may benefit from this combination therapy. PMID- 26882571 TI - [Distribution of virulence genes and PFGE molecular typing of Entero-hemorrhagic Escherichia coli O157 in Henan from 2009- 2010]. PMID- 26882572 TI - [Multilocus sequence typing of Campylobacter jejuni isolates from Guizhou province]. PMID- 26882573 TI - Get Smart About Antibiotics Week -- November 16-22, 2015. PMID- 26882574 TI - Prescription Drug Abuse is a Major Public Health Problem. PMID- 26882575 TI - A Reminder to Our Patients and Ourselves. PMID- 26882576 TI - State of South Dakota's Child: 2015. AB - In 2014 there was an increase in the number of births in the state with 24 percent representing minority populations. This year also brought a decrease from 2013 in deaths for infants, yielding an infant mortality rate of deaths per 1,000 live births (5.9) slightly below that of the most current national rate of 6.0 in 2013. Consistent with previous years, disparities persist in rates of death for white and minority infants with 45 percent of 2014 infant deaths (versus 24 percent of the births) represented by minorities. Between 2010 and 2014, 57 percent of white and 60 percent of minority post neonatal deaths in South Dakota were attributable to sudden unexpected infant death, accidents and homicide for both whites and minorities. The rates of infant deaths due to these causes, however, were significantly higher (p < .01) for minorities than for whites. PMID- 26882577 TI - Managing H*V in Pregnancy. AB - A number of chronic viral infections require special attention during pregnancy in the prenatal, perinatal and postnatal periods. In many rural areas of South Dakota, these conditions are present, but readily-accessible subspecialty consultation is not. Fortunately, most aspects of management of these conditions in pregnancy are easily within the scope of practice of primary care physicians. This paper presents a review of the management of pregnancies complicated by HBV, HCV, HIV, HPV and HSV, offering a quick-reference guide for physicians who may infrequently encounter these patients as a part of their practices. PMID- 26882578 TI - Osteonecrosis of the Torus Palatinus in the Setting of Long-Term Oral Bisphosphonate Use--A Case Report. AB - Bisphosphonates are medications used orally and intravenously for a variety of conditions including cancer metastatic to bone, hypercalcemia of malignancy, Paget's disease and osteoporosis. Osteonecrosis of the jaw has been related to bisphosphonate use. Osteonecrosis of the jaw most commonly occurs in the setting of intravenous bisphosphonate use and concomitant dental work or trauma. Oral bisphosphonates have much less risk of osteonecrosis of the jaw. We present an interesting case of a patient on an oral bisphosphonate for an extended period of time (nine years), with a torus palatinus, who burned her palate while eating a slice of pizza. Over six months later, she presented with an area of denuded bone and diagnosis consistent with osteonecrosis of the torus palatinus. PMID- 26882579 TI - A Case of Hepatotoxicity Related to Kombucha Tea Consumption. AB - The use of herbal and dietary supplements (HDSs) is widespread and growing due to the popular notion that these products are of natural origins and safe. Kombucha (or "mushroom") tea is one HDS that is consumed by people for various perceived health benefits. Kombucha tea is a well-known health beverage made by fermenting sweet black tea with a round, flat, gray fungus for a week or longer. There is concern, however, from the evidence of a few case reports currently available, that it may pose life-threatening and/or adverse effects for users. PMID- 26882580 TI - Early Onset Sepsis. AB - Early onset sepsis (EOS) is a worrisome, life-threatening condition in newborns with onset during the first week of life. Evaluation can be challenging due to the dynamic nature of the condition as the infant transitions to life ex-utero. Symptoms/signs can be nonspecific, thus, a high index of suspicion is warranted for subtle changes in condition including poor feeding, respiratory distress, or decreased activity. Common risk factors include chorioamnionitis, maternal fever, group B strep (GBS) colonization and preterm delivery. Despite universal screening and intrapartum antibiotic prophylaxis (IAP), GBS remains the most frequent cause of EOS followed by Escherichia coli (E. coli). While the gold standard for diagnosis remains a positive blood culture, lab evaluation frequently involves complete blood count (CBC) with differential, c-reactive protein (CRP), and evaluation of spinal fluid if the infant is stable. Unfortunately, there is not a lab test that is rapidly diagnostic for sepsis, so treatment should be empirically started until it is clear that the infant is not infected. Treatment often includes ampicillin and gentamicin for coverage of the most frequent pathogens. There is much debate about timing of discontinuation of antibiotics. Frequently, antibiotics can be discontinued after 48 hours in well appearing, asymptomatic infants with negative blood cultures and either normal CBC analysis or normal CRP values. PMID- 26882581 TI - How Low Can You Go? What Can We Take From the SPRINT Trial. PMID- 26882583 TI - Patient Education: Key to the Treasure. PMID- 26882582 TI - DAKOTACARE Update: Genetic Counseling Requirement for BRCA 1/2 Testing. PMID- 26882584 TI - Quality Focus: Physician Reimbursement Change. PMID- 26882585 TI - VIOLENCE, SAFETY AND PHYSICIAN LEADERSHIP. PMID- 26882586 TI - CRIME SCENE INVESTIGATION: HOSPITAL VIOLENCE! PMID- 26882587 TI - FUNDAMENTALS OF PATIENT SATISFACTION MEASUREMENT. PMID- 26882588 TI - SUCCESSFUL INTERVIEWING: DON'T LOSE THE BIG GAME. PMID- 26882589 TI - MAKING A MID-CAREER TRANSITION. PMID- 26882590 TI - IF YOU WANT LESS OF SOMETHING, TAX IT: THE BATTLE OVER THE CADILLAC TAX. PMID- 26882591 TI - BALANCING SCIENCE AND SERVICE: THE PHYSICIAN LEADER'S ROLE. PMID- 26882592 TI - HEALTH CARE TRANSFORMATION: FROM SERVICE LINES TO PROGRAMS. PMID- 26882594 TI - BUILDING THE MENTAL MODEL FOR LEADERSHIP. PMID- 26882593 TI - AVOIDING MISSTEPS IN THE POPULATION HEALTH JOURNEY. PMID- 26882595 TI - ARE YOU EMPATHETIC? PMID- 26882596 TI - COACHING: A USEFUL APPROACH TO DISRUPTIVE BEHAVIOR. PMID- 26882597 TI - ENHANCING HUMAN PERFORMANCE FOR BETTER HEALTH CARE OUTCOMES. PMID- 26882599 TI - [Present Routes of Integrating Chinese Medicine and Western Medicine: Converging and Cooperating]. PMID- 26882598 TI - [Inheritance, Innovation, and Developing Trace of Modern Blood Activating Stasis Removing School]. PMID- 26882600 TI - [Exploration of Cooperatively Innovating Systems for National Clinical Research Base of Chinese Medicine]. PMID- 26882601 TI - [Status, Challenges, and Prospects of Treating Chronic Atrophic Gastritis by Chinese Medical Diagnosis and Treatment]. AB - Chronic atrophic gastritis (CAG), a chronic disease of the digestive system resulting from multi-pathogenic factors, is precancerous state of gastric cancer. Authors reviewed the current situation of Chinese medical diagnosis and treatment of CAG, and looked forward to its prospect by combining with their own clinical experience and scientific researches. PMID- 26882602 TI - [Metabonomics Study on Urine 1H-NMR in Chronic Superficial Gastritis Patients with Pi-qi Deficiency Syndrome/Pi-Wei Dampness-heat Syndrome]. AB - OBJECTIVE: To observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them. METHODS: Urine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis. RESULTS: PLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, alpha oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, beta-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid. CONCLUSION: The metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing. PMID- 26882603 TI - [Correlation Study on Chinese Medical Syndrome Types of Chronic Atrophic Gastritis Patients, Hp, and IL-1beta Polymorphism]. AB - OBJECTIVE: To explore the correlation between Chinese medical (CM) syndrome types of chronic atrophic gastritis (CAG) patients and Helicobacter pylori (Hp) infection, polymorphisms of IL-1B, and IL-1beta. METHODS: Totally 192 CAG patients and 202 healthy subjects (as the healthy control group) were recruited in this case-control study. The Hp infection was tested by 13C-urea breath test and colloidal gold-labeled assay (GICA). The concentration of peripheral blood IL 1beta was measured by ELISA. The polymorphisms of IL-1B gene in the promoter region were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Pi-Wei weakness syndrome (PWWS) was dominant in CAG patients (31.77%, 61/192 cases). The Hp infection ratio in CAG patients was 53.65% (103/192 cases), of which, Pi-Wei damp-heat syndrome(PWDHS, 64.86%, 24/37 cases) and Gan-Wei disharmony syndrome (GWDS, 66.67%, 24/36 cases) were dominant. Compared with the health control group, the plasma concentration of IL-1beta was obviously elevated in CAG patients with PWDHS, GWDS, and static blood obstructing collaterals syndrome (SBOCS) (all P < 0.05). Additionally, there was no difference in the distribution of polymorphisms in the promoter region of IL-1 B gene between the CAG patients and the healthy control group (P > 0.05). CONCLUSIONS: The incidence risk of CAG was not associated with IL-1B polymorphism. But CM syndrome types of CAG patients was associated with Hp infection and peripheral blood IL-1beta levels. PMID- 26882604 TI - [Effect of Yiqi Huoxue Qingre Huashi Recipe on the Eradication Rate of Hp in Peptic Ulcer Patients]. AB - OBJECTIVE: To observe the effect of Yiqi Huoxue Qingre Huashi Recipe (YHQHR, a recipe capable of supplementing qi, activating blood, clearing heat, and dissipating dampness) on ulcer healing and Helicobacter pylori (Hp) eradication rate in Hp positive peptic ulcer patients, and to explore coccoid Hp occurrence in the eradication. METHODS: Totally 80 Hp positive peptic ulcer patients were assigned to the treatment group and the control groups by random digit table, 40 in each group. All patients received standard triple therapy of Western medicine for 2 successive weeks. Those in the control group additionally took omeprazole enteric coated tablet, 20 mg each time, once per day for 4 successive weeks. Those in the treatment group additionally took YHQHR, twice per day for 6 successive weeks. The ulcer healing was observed and recorded by gastroscope after discontinued medication of 14 days. The effective rate of ulcer healing under endoscope was statistically calculated. Rapid urease test (RUT) was performed in one small piece of tissue from corpora ventriculi and sinuses ventriculi using 14C breathe test (UBT). Gastric juice was collected from the stomach. Hp urease gene amplification test (urea A-PCR) was performed in living tissue from gastric antrum. Results obtained from the above three test methods were recorded and assessed to decide the final eradiation rate. Gastric mucosa tissue was observed under electron microscope,attempting to find non-eradicated Hp, which was further observed. RESULTS: The total curative effect under gastroscope was 97.5% (39/40 cases) in the treatment group, obviously higher than that in the control group (80.0%, 32/40 cases) (P < 0.05). The eradication rate of Hp was 75.0% (30/40 cases), obviously better than that of the control group (52.5%, 21/40 cases) (P < 0.05). The total positive Hp numbers after treatment was 14C UBT (12), RUT (8), and urea A-PCR (27), respectively. The Hp positive rate detected by 14C UBT and RUT was lower than the Hp positive rate detected by urea A-PCR (P < 0.05). Rod-like and coccoid Hp bacteria could be observed under electron microscope. CONCLUSION: YHQHR combined standard triple therapy was more effective than standard triple therapy alone in promoting ulcer healing and elevating the eradication rate of Hp. PMID- 26882605 TI - [Clinical Analysis of Drug-induced Liver Injury Caused by Polygonum multiflorum and its Preparations]. AB - OBJECTIVE: To analyze hepatotoxicity of Polygonum multiflorum and clinical character- istics of drug-induced liver injury (DILI) caused by Polygonum multiflorum and its preparations. METHODS: A retrospective study was performed in 158 patients treated at 302 Military Hospital between January 2009 and January 2014. All of them had used Polygonum multiflorum and its preparations before the onset of DILI, and their clinical characteristics and prognoses were analyzed. RESULTS: Of the 158 DILI patients who used Polygonum multiflorum or its preparations, 92 (58.2%) combined with Western medicine or Chinese herbal preparations without Polygonum multiflorum; 66 patients (41.8%) used Polygonum mult florum and its preparations alone. In 66 DILI patients induced by Polygonum multiflorum or its preparations alone, 51 cases (77.3%) were induced by Polygonum multiflorum compounds and 22.7% by single Po- lygonum multiflorum; 4 cases (6.1%) were caused by crude Polygonum multiflorum and 62 (93.9%) by processed Polygonum multiflorum and its preparations. Clinical injury patterns were hepatocellular 92.4% (61 cases), cholestatic 1.5% (1 case), and mixed 6.1% (4 cases). Pathological examination was per- formed by liver biopsy in 32 cases (48.15%), manifested as hepatocellular degeneration and necrosis, fibroplasia, Kupffer cells with pigment granule, and a large number of eosinophil infiltration, were ob- served. Four patients were developed into liver failure, 4 into cirrhosis, and 1 died. CONCLUSION: Polygo- num multiflorum and its preparations could induce DILI, but clinical diagnosis of Polygonum multiflorum induced hepatotoxicity should be cautious. PMID- 26882606 TI - [Methylation in Promoter Region of SLC6A2 Gene in Heart Failure Patients and Its Correlation with Qi Deficiency/Blood Stasis Syndrome]. AB - OBJECTIVE: To explore the methylation status in promoter region of norepinephrine transporter gene (NET, SLC6A2) in heart failure ( HF) patients and its correlation with qi deficiency/blood stasis syndrome (QDS/BSS). METHODS: Thirty six patients with heart failure (NYHA classification III to IV) were recruited in the study (as the heart failure group) and their scores of QDS/BSS were evaluated. Besides, a healthy elderly group (30 cases) and a healthy youth group (30 cases) were also set up. They were recruited from Physical Examination Center of Fujian Provincial Hospital. Pyrosequencing was applied to detect the methylation in promoter region of SLC6A2 gene, and the total methylation index (MTI) of CpG island was calculated. The correlation between the methylation status in promoter region of SLC6A2 and scores of QDS/BSS was assessed using Pearson and Partial analyses. Risk factors were screened and adjusted using Logistic regression. RESULTS: By one-factor analysis of variance, the total MTI in the HF group (219.72% +/- 54.03%) was obviously higher than that in the healthy elderly group (194.47% +/- 34.92%) and the healthy youth group (161.60% +/- 41.11%) (all P < 0.05). Meanwhile, the total MTI was higher in the healthy elderly group than in the healthy youth group (P < 0.01). By covariance analysis , after controlling age and BMI, the total MTI was higher in the HF group than in the healthy elderly group (P = 0.041), while it was higher in the healthy elderly group than in the healthy youth group (P = 0.016). Age was found to play an essential role in affecting MTI of SLC6A2 gene promoter region among the 3 groups (F = 16.447, P = 0.01). The total MTI was quite lower in the healthy youth group. Results of Partial correlation analysis showed MTI was positively correlated with scores of qi deficiency and blood stasis respectively (r = 0.494 and 0.419 respectively, both P < 0.05). Logistic regression analysis showed after adjusting confounding factors, the relative risk (OR value) of total MTI of SLC6A2 gene in promoter region was 1.038 (95% CI, 1.006 to 1.071, P = 0.020). CONCLUSIONS: Abnormally elevated methylation of the promoter region of SLC6A2 gene is one of risk factors for HF. In addition, the degree of methylation of the promoter region of SLC6A2 gene was positively correlated with the severity of QDS/BSS. PMID- 26882607 TI - [Treatment of Infective Ulcer Patients with Yang Syndrome by External Use of Shengji Ointment: a Multicenter Randomized Controlled Trial]. AB - OBJECTIVE: To evaluate the safety and effectiveness of Shengji Ointment (SO) (by external use) in treating infective ulcer patients with yang syndrome (YS). METHODS: A multicenter, stratified, randomized controlled clinical study was used in this study. A random digit table was formed in the ratio of 3:1,440 infective ulcer patients of YS from 5 centers were recruited, 330 in the treatment group (external use of SO, exchange once every 24 h) and 110 in the control group (external use of Votalin, exchange once every 24 h). The therapeutic course consisted of 21 days. The ulcer area, wound depth, pain degree were observed before treatment at day 3, 7, 14, and 21, and safety indices monitored at the same time. RESULTS: The ulcer area was significantly reduced in the treatment group after 21-day medication, obviously superior to that of the control group (P = 0.002). Ulcer areas at different time points were analyzed. From the 7th day of medication the reduced area was obviously less in the treatment than in the control group (P = 0.002). Besides, the longer the more obvious difference. Compared with the control group, the healing rate of ulcer area, the pain disappearance rate, and the healing rate of ulcer depth were all obviously improved in the treatment group (all P < 0.01). No adverse event occurred in the two groups. CONCLUSIONS: External use of SO was safe and effective in treating infective ulcer patients with YS. It could accelerate wound healing with better analgesic effect. PMID- 26882608 TI - [Evaluation on Efficacy and Safety of Jinying Capsule in Treatment of Pelvic Inflammatory Disease Patients with Accumulated Damp-heat Syndrome]. AB - OBJECTIVE: To evaluate the efficacy and safety of Jinying Capsule (JC) in treating pelvic inflammatory disease patients with accumulated damp-heat syndrome (ADHS). METHODS: Totally 328 patients were recruited in a prospective, positive drug parallel controlled, and multi-center clinical trial. Of them 213 patients in the treatment group took JC (0.5 g per capsule), 4 capsules each time, 3 times per day, while 115 patients in the control group took Kangfuyan Capsule (KC, 0.4 g per capsule), 3 capsules each time, twice per day. The course of treatment was 4 weeks for all. Scores of Chinese medical syndromes, visual analogue scale (VAS) of the lower abdominal pain, and European quality of life-five dimension scale (EQ-5D) were observed before treatment and after 4 weeks of treatment. RESULTS: There were 204 patients in the treatment group and 109 in the control group who completed this trial. The total effective rate of Chinese medical syndrome was 89.71% (183/204 cases) in the treatment group and 76.15% (83/109 cases) in the control group (P < 0.01). Compared with before treatment in the same group, EQ-5D scores increased, and VAS scores of the lower abdominal pain decreased in the two groups after treatment. EQ-5D scores was 0.857 +/- 0.157 in the treatment group, obviously higher than that in the control group (0.753 +/- 0.126, P < 0.05). VAS scores of the lower abdominal pain was 2.14 +/- 1.23 in the treatment group, lower than that in the control group (2.33 +/- 1.24), but with no statistical difference between the two groups (P > 0.05). No adverse reaction occurred in the two groups. CONCLUSION: JC was superior to KC in improving Chinese medical syndrome and quality of life of pelvic inflammatory disease patients with accumulated damp-heat syndrome. PMID- 26882609 TI - [Effects of Acupuncture on Neurofunction and Neuropsychological Factors of Chronic Alcoholic Peripheral Neuropathy Patients]. AB - OBJECTIVE: To observe the effects of acupuncture on neurofunction and neuropsychological factors of chronic alcoholic peripheral neuropathy (CAPN) patients. METHODS: Totally 120 CAPN patients were assigned to the common treatment group, acupuncture group A, and acupuncture group B according to random digit table, 40 in each group. All patients recieved conventional drug therapy. Besides, patients in the acupuncture group A were additionally needled at Pishu (BL20), Weishu (BL21), Xuehai (SP10), Yinlingquan (SP9), Zusanli (ST36), Yanglingquan (GB34), Jiexi (ST41), Xuanzhong (GB39), Xiangu (ST43),Taixi (KI3), Quchi (LI11), Waiguan (SJ5), Hegu (LI4), and so on. On these bases patients in the acupuncture group B were needled at Sishencong (EX-HN1), Yintang (EX-HN3), Neiguan (PC6), Taichong (LR3), Sanyinjiao (SP6), and Taiyang (EX-HN5). Acupuncture was performed once a day, 14 times as a course; and then once on every other day, 14 times in total for 4 weeks. All treatment lasted for 8 successive weeks. Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Neurological Severity Score (NSS), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA) were assessed, motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) were detected before and after treatment. RESULTS: After 8 weeks of treatment the scores of NIS-LL and NSS significantly decreased in the 3 groups, with statistical difference as compared with before treatment (P < 0.05). Scores of NIS-LL and NSS decreased more in acupuncture groups A and B than in the common treatment group (P < 0.05), and more obvious in acupuncture group B (P < 0.05). Compared with the same group before treatment, MCV and SCV of median nerve, ulnar nerve, common peroneal nerve and tibial nerve increased in acupuncture treatment group A and B after 8-week treatment (P < 0.05). MCV of median nerve, MCV and SCV of common peroneal nerve and tibial nerve significantly increased in the common treatment group (P < 0.05). Compared with the common treatment group, SCV of median nerve, MCV and SCV of ulnar nerve, common peroneal nerve and tibial nerve obviously increased in acupuncture treatment groups A and B after treatment (P < 0.05). MCV of ulnar nerve, MCV and SCV of common peroneal nerve and tibial nerve obviously increased more in acupuncture treatment group A than in acupuncture treatment group B (P < 0.05). At week 8 after treatment scores of HAMD and HAMA were obviously lowered in acupuncture groups A and B, with statistical difference as compared with before treatment (P < 0.05). The scores of HAMD were also decreased in the common treatment group, as compared with before treatment (P < 0.05). At week 8 after treatment scores of HAMD and HAMA were obviously lowered more in acupuncture treatment group B than in acupuncture treatment group A (P < 0.05). CONCLUSION: Acupuncture therapy could effectively improve the neurofunction of CAPN patients, and improve complicated anxiety and depression by additionally needling at Sishencong (EX-HN1), Yintang (EX-HN3), Taichong (LR3), Sanyinjiao (SP6), and Taiyang (EX-HN5). PMID- 26882610 TI - [Analysis of Applying Chinese Medical Clinical Pathway for Treating Attention deficit Hyperactivity Disorder]. AB - OBJECTIVE: To evaluate the application effect of Chinese medical clinical pathway for treating attention-deficit hyperactivity disorder (ADHD), and to provide evidence for further improving clinical pathways. METHODS: Totally 270 ADHD children patients were recruited and treated at pediatrics clinics of 9 cooperative hospitals from December 2011 to December 2012. The treatment course for all was 3 months. Scores of attention deficit and hyperactivity rating scale, scores of behavior, Conners index of hyperactivity (CIH), and Chinese medical syndrome scores were compared between before and after treatment. The efficacy difference in various sexes, ages, and disease courses were evaluated by judging standards for Chinese medical syndrome and ADHD. RESULTS: Fifteen children patients who entered clinical pathway dropped out, and the rest 255 completed this trial. Compared with before treatment, total scores of attention deficit and hyperactivity rating scale, scores of attention deficit and hyperactivity rating scale, CIH, and Chinese medical syndrome scores obviously decreased (all P < 0.01). The total effective rate in disease efficacy was 87.8% (224/255 cases), and the total effective rate in Chinese medical syndrome curative effect was 87.5% (223/255 cases). The clinical curative effect was not influenced by age, gender, or course of disease when statistically analyzed from judging standards for Chinese medical syndrome or for disease efficacy. CONCLUSION: Intervention by Chinese medical clinical pathway could improve ADHD patients' symptoms, and its efficacy was not influenced by sex, age, or course of disease. PMID- 26882611 TI - [Intervention Mechanism of Extracts from Radix Ginseng, Radix Notoginseng and Rhizoma Chuanxiong on Adventitia of Senescent Rats]. AB - OBJECTIVE: To observe the reconstruction features of adventitia in senescent rats, and to explore the intervention mechanism of Chinese herbs (CH, extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong). METHODS: Totally 85 20-month senescent rats were randomly divided into 5 groups according to body weight, i.e., the aging model group, the high dose CH group, the middle dose CH group, the low dose CH group, the Losartan group, 17 in each group. Another 14 2 month old Wistar rats were selected as a young group. Extracts of CH at the daily dose of 1493. 4, 746. 7, and 373. 4 mg/kg were administered to rats in the 3 CH groups respectively by gastrogavage. Losartan suspension at the daily dose of 10 mg/kg was administered to rats in the Losartan group by gastrogavage. Equal volume of distilled water was administered to rats in the aging model group and the young group. All medication was performed once daily. After 15-week intervention, morphological changes of thoracic aorta were observed by HE staining. The types, distribution, and contents of vessel wall collagens were determined using picric acid picrosirius red staining. The plasma renin activity (PRA) , the concentration of rennin angiotensin II (Ang II), and the content of Ang II in adventitia were detected by radioimmunoassay. The content of hydroxyproline ( Hyp) was detected by biochemical analysis. mRNA contents and protein expressions of angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R) were detected by real-time PCR (RT-PCR) and Western blot. RESULTS: Compared with the young group, thickened adventitia, increased adventitia thickness/caliber, accumulated collagen fiber, increased area of type I collagen, decreased area of type III collagen, decreased type III/I collagen area ratio (P <0. 05), decreased plasma PRA and Ang II (P < 0.01, P < 0.05), increased contents of Ang II and Hyp in adventitia, down-regulated mRNA and protein expressions of AT1R, and up-regulated mRNA and protein expression of AT2R could be seen in the aging model group (P < 0.05). Compared with the aging model group, morphological changes could be improved in the 3 CH groups. Adventitia thickness/caliber was reduced in middle and high dose CH groups, as well as the Losartan group. The area of type I collagen was reduced and the area of type III collagen was enlarged, type III/I collagen area ratio obviously increased, contents of adventitia Hyp was obviously lowered in the high dose CH groups and the Losartan group (P < 0.05, P < 0.01). Ang II levels in adventitia decreased in middle and high dose CH groups and the Losartan group (P < 0.05, P < 0.01). There was no statistical difference in PAR among all groups (P > 0.05). Compared with the aging model group, mRNA expression of AT1R all increased in each treatment group (P < 0.01); mRNA expression of AT2R also increased in middle and high dose CH groups (P < 0.05). Protein expression of AT1R increased in the high dose CH group and the Losartan group (P < 0.01, P < 0.05); protein expression of AT2R also increased in middle and high dose CH groups (P < 0.05). CONCLUSIONS: Adventitia remodeling occurred in aged rats, manifested as thickened adventitia and accumulated collagens, disordered ratios of collagen I and III. Its mechanism might be possibly associated with aactivation of renin-angiotensin system (RAS). Extracts from Radix Ginseng, Radix Notoginseng, and Rhizoma Chuanxiong could improve adventitial remodeling possibly by interfering multi-targets, such as Ang II and AT1R, thereby delaying vascular aging. PMID- 26882612 TI - [Intervention Effect of Modified Dachengqi Decoction on Intestinal Mucosal Barrier of Severe Acute Pancreatitis Model Rats]. AB - OBJECTIVE: To study the effect of Modified Dachengqi Decoction (MDD) as whole course therapy on mediators of inflammation in severe acute pancreatitis (SAP) model rats, and to compare interventional advantages over intestinal mucosal barrier (IMB) of SAP rats between whole course therapy of MDD and early stage therapy of MDD. METHODS: Totally 190 SD rats were divided into five groups according to random digit table, i.e., the sham-operation group, the model group, the octreotide (OT) group, the early stage MDD treatment group, the whole course MDD treatment group, 38 in each group. SAP models were established with retrograde injection of 5% sodium taurocholate into the pancreaticobiliary duct. Three hours after modeling normal saline (NS) was administered to rats in the sham-operation group and the model group by gastrogavage, once per 12 h.1.35 ug/100 g OT was subcutaneously injected to rats in the OT group, once every 8 h. 0.4 mL/100 g MDD was administered to rats in the early stage MDD treatment group, and 6 h later changed to NS (once per 12 h).0.4 mL/100 g MDD was administered to rats in the whole course MDD treatment group, once every 12 h. The accumulative survival rate and morphological manifestations of pancreas and small intestine were observed under microscope 48 h after modeling. Pathologic scores of the pancreas and small intestine were conducted at 4, 6, 24, and 48 h after modeling. Contents of serum amylase (AMY), alanine transaminase (ALT), and TNF-alpha were also detected. The expression of high mobility group box protein 1 (HMGB1) in the small intestine tissue was also detected by Western blot. The positive rate of bacterial translocation in mesenteric lymph nodes (MLNs) was observed within 48 h. Correlations between serum TNF-alpha or HMGB1 in small intestinal tissue and pathological scores of the pancreas or the small intestine were analyzed. RESULTS: The accumulative survival rate was 100. 0% in the sham-operation group, 79. 2% in the whole course MDD treatment group, 70. 8% in the OT group, 45. 8% in the early stage MDD treatment group, and 37.5% in the model group. At 6 h after modeling, pathological scores decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 24 and 48 h after modeling, pathological scores of the pancreas and the small intestine decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P <0. 05). At 6, 24, and 48 h after modeling, serum contents of AMY and ALT both decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 48 h after modeling serum contents of AMY and ALT both decreased more in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). At 6 h after modeling serum TNF-alpha levels decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). At 6, 24, and 48 h after modeling the level of HMGB1 in the small intestinal tissue decreased more in the whole course MDD treatment group, the early stage MDD treatment group, the OT group than in the model group (P < 0.05). Of them, HMGB1 levels at 24 and 48 h were lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group (P < 0.05). The number of MLNs bacterial translocation at 48 h after modeling was lower in the whole course MDD treatment group and the OT group than in the early stage MDD treatment group and the model group (P < 0.05). Serum TNF-alpha contents within 6 h were positively correlated with pathological scores of pancreas (r = 0.579, P < 0.01). ROC curve showed that serum TNF-alpha contents could predict the severity of SAP (ROC = 0.990, 95% Cl: 0.971 to 1.000). HMGB1 in the small intestine was positively correlated with pathological scores of the small intestine (r = 0.620, P < 0.01). CONCLUSIONS: Early stage use of MDD could effectively reduce the release of TNF-alpha, while whole course use of MDD could effectively inhibit the expression of HMGB1. The latter could preferably attenuate injuries of the pancreas and the small intestine, lower MLNs bacterial translocation, and elevate the survival rate. PMID- 26882613 TI - [Effect of Peimine on ERCC1 mRNA and LRP Expressions of A549/DDP Multidrug Resistance Cell Line]. AB - OBJECTIVE: To explore the effect of peimine on excision repair cross complementation 1 (ERCC1) mRNA and lung resistant protein (LRP) expressions in A549/cisplatin (DDP) multidrug resistance (MDR) cell line. METHODS: Lung cancer A549/DDP cells were cultured in vitro.Cells at logarithmic growth phase were divided into 4 groups, i.e., the blank control group, the DDP group, the ligustrazine group (DDP+ligustrazine), the peimine group (DDP + peimine). After 48-h drug action, ERCC1 mRNA expression was detected by RT-PCR and LRP expression detected by cell immunofluorescence. RESULTS: There was no statistical difference in expression levels of ERCC1 mRNA and LRP between the DDP group and the blank control group (P > 0.05). Compared with the DDP group, expression levels of ERCC1 mRNA and LRP obviously decreased in the ligustrazine group and the peimine group (P < 0.05). They were obviously lower in the peimine group than in the ligustrazine group (P < 0.05). CONCLUSIONS: Peimine could reverse MDR of A549/DDP cell line. Its mechanism might be associated with down-regulating ERCC1 mRNA and LRP expression levels. PMID- 26882614 TI - [Effect of Buyang Huanwu Decoction on mRNA Expressions of Aorta Rho Kinase and NF kappaB p65 in Atherosclerosis Model Rats]. AB - OBJECTIVE: To observe the effect of Buyang Huanwu Decoction (BYHWD), a representative formula of qi benefiting blood activating method on aorta Rho associated coiled-coil forming protein serine/threonine kinase (Rhokinase, ROCK) and nuclear transcription factor kappa B (NF-kappaB) p65 mRNA expressions and levels of blood lipids in atherosclerosis (AS) model rats. METHODS: The AS rat model was prepared by vitamin D3 and high fat diet. Totally 60 rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the low dose BYHWD group (10 g/kg), the high dose BYHWD group (20 g/kg), the Simvastatin control group (0.6 mg/kg), and the BYHWD prevention group (10 g/kg), 10 in each group. After successful modeling all medication was intervened for 28 days. Expression levels oxidized low density lipoprotein (ox-LDL) were detected by ELISA. Levels of TG, TC, LDL-C, HDL-C were determined by enzyme method. Pathological changes of aortic tissue were observed under light microscope. mRNA expressions of Rho kinase and NF-kappaB p65 in aorta were detected by real time (RT) PCR. RESULTS: High fat diet and peritoneal injection of vitamin D3 could induce AS rat model. Typical atheromatous plaque formed in aorta of AS model rats. Compared with the normal control group, levels of TC, TG, LDL-C, and ox-LDL significantly increased in the model group, but the HDL-C level decreased (P < 0.01). Compared with the model group, levels of TC, TG, LDL-C, and ox-LDL all decreased, but HDL-C increased in low and high dose BYHWD groups, the Simvastatin control group, and the BYHWD prevention group (P < 0.05, P < 0.01). Compared with the low dose BYHWD group, above-mentioned indices were more obviously lowered in the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P < 0.05). Compared with the normal control group, mRNA expression levels of Rho kinase and NF-kappaB p65 significantly increased in the model group (P < 0.01). Compared with the model group, mRNA expressions of Rho kinase and NF-kappaB p65 obviously decreased in low and high dose BYHWD groups, the Simvastatin control group, and the BYHWD prevention group (P < 0.01). Compared with the low dose BYHWD group, the two indicators were more obviously lowered in the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P < 0.05). But there was no statistical difference in blood lipids levels, mRNA expression levels of Rho kinase or NF-kappaB p65 among the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P >0. 05). CONCLUSIONS: BYHWD could down-regulate mRNA expression levels of Rho kinase and NF-kappaB p65, lower levels of blood lipids, and fight against AS. Suppressing Rho kinase pathway might be one of its mechanisms. PMID- 26882615 TI - [Pharmacokinetic Effect of Aikeqing Granule by Different Medication Ways on Zidovudine in HAART of Rats]. AB - OBJECTIVE: To study pharmacokinetic effect of Aikeqing Granule (AG) by different medication ways on zidovudine (AZT) in highly active antiretroviral therapy ( HAART) of rats. METHODS: Totally 36 rats were administered with corresponding medications by gastrogavage, group I [HAART: AZT 31.5 mg/kg +3TC 31.5 mg/kg + Efavirenz (EFV) 63.0 mg/kg], group II (HAART+AG525 mg/kg), group III (HAART and AG 525 mg/kg after a 2-h interval). Drug concentrations of AZT were determined by high performance liquid chromatography-mass spectroscopy (HPLC-MS) before HAART, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12 h after HAART, respectively. Pharmacokinetic parameters [such as t1/2, Tmax, Cmax, AUCo-t, plasma clearance rate (CL)] were calculated by DAS2.0 Software. RESULTS: The-equation of linear regression of AZT was good, with the precision, coefficient of recovery, and stability definitely confirmed. AUC in group II and III was larger than that of group I. There was no statistical difference in t1/2, Tmax, Cmax, AUC0-12 h, or AUC0-infinity among groups (P > 0.05). CONCLUSION: AG combined HAART could enhance the Cmax of AZT. PMID- 26882616 TI - [Xianglian External Lotion Restored the Sensitivity of Drug-resistant Candida albicans Strains to Fluconazole: a Transcriptomics Study]. AB - OBJECTIVE: To perform a transcriptomics study in differential genes after Xianglian External Lotion (XEL) induced the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole. METHODS: Broth microdilution antifungal susceptibility test was used to detect minimal inhibitory concentration (MIC) of drug-resistant Candida albicans strains induced by XEL. Transcriptome sequencing (RNA-Seq) was used to determine and compare the transcription of primary drug-resistant Candida aIbicans strains and sensitive strains induced by XEL. High expressed genes and signaling pathways strains were analyzed by gene ontology (GO) method. RESULTS: XEL could induce drug-resistant strains of the 6th generations to recover sensitivity. Transcriptome sequencing showed that, as compared with primary drug-resistant strains, there were 165 genes with up-regulated RPKM index and 144 genes with down-regulated RPKM index after XEL induction. GO analyses found that all genes were mainly classified as GO:0015903 (fluconazole transport). CONCLUSIONS: XEL could induce the recovery of drug-resistant Candida albicans strains sensitive to Fluconazole. By analyzing transcriptomes, authors speculated that XEL could recover strain sensitivity to fluconazole by opening fluconazole transport pathway. PMID- 26882617 TI - [Effect of Culture-loaded Words on English Translation of Chinese Medical Formulae--from the translation of "lozenge"]. PMID- 26882618 TI - [Research on Collateral-unblocking Medicines for Cardiovascular Diseases under the Guidance of Vessels Collateral Theory]. AB - OBJECTIVE: "Vessels Collateral Theory", as the inherit and development of "blood vessels" in Huangdi Neijing, is a systematic system by integrating severe vascular diseases. In this article, by taking cardiovascular diseases (CVD) as a cut-in point, roles of "minute collateral-microvascular" lesions in the occurrence and development of CVD were further explored. The interventional effect of collateral-unblocking medicines under the guidance of Vessels Collateral Theory was also in-depth explored, hoping to leading Chinese medical prevention and treatment of CVD. PMID- 26882619 TI - [Reflection on Medical Treatment of Multi-drug Resistance Tuberculosis: The Necessity of Chinese Medicine Holistic View]. AB - Causative factors of multi-drug resistance tuberculosis (MDR-TB) were analyzed from iatrogenic angles, patients themselves, and society. Reviewed was the development of treatment strategies for MDR-TB from directly observed treatment short-course (DOTS) to DOTS-Plus. The history of Chinese medicine (CM) fighting TB and characteristics at the present stage were also analyzed. Authors pointed out that CM pays attention not only to killing pathogens and confirms the necessity of getting rid of pathogens, but also to cascade response caused by pathogens. It also regards the occurrence and development of MDR-TB as a whole by combining patients' conditions, climatic, geographic, psychological, and social factors. Authors believed that therapeutic principles under guidance of CM holistic view are of positive significance and inspiration in treating MDR-TB, and emphasized holistic view as basic strategies for treating MDR-TB, but not a single countermeasure. PMID- 26882620 TI - [Adverse reactions occurred in four cases induced by intravenous injection of Alprostadil and Shuxuening Injection in normal saline]. PMID- 26882621 TI - [Treatment of Primary Sjogren's Syndrome Complicated Nephritis of Henoch Schonlein Purpura: a Case Report of One Case]. PMID- 26882622 TI - [On Radix Aconiti Lateralis and Kidney Diseases]. PMID- 26882623 TI - Drug Pricing Regulation Pushed From Many Sides. PMID- 26882624 TI - Life in the Fast Track. PMID- 26882625 TI - UNTANGLING THE HIE MESS. PMID- 26882626 TI - Next Generation ACOs Must Defy FFS Gravity. PMID- 26882627 TI - Narrow Networks Discussion Turns on Degree, Execution. PMID- 26882628 TI - A CONVERSATION WITH VINCENT DEVITA, MD. No Truce Sought in Cancer War: 'We Want to Cure This Disease'. PMID- 26882629 TI - Improved Spine Care Means Giving Physiatrists Playing Time. PMID- 26882630 TI - Prescription Omega-3 Fatty Acid Products and Dietary Supplements Are Not Interchangeable. AB - PURPOSE: To provide an overview of prescription and dietary supplement omega-3 fatty acid (OM3-FA) products and considerations for clinical use. DESIGN: Narrative review. METHODOLOGY: The PubMed database was searched for cardiovascular-related investigations focused on eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) (limit: English-only articles). Additional regulatory information on prescription and dietary supplements was obtained from United States Food and Drug Administration online sources. RESULTS: Prescription QM3-FA products are supported by robust clinical development and safety monitoring programs, whereas dietary supplements are not required to demonstrate safety or efficacy prior to marketing. There are no over-the-counter OM3-FA products available in the United States. Investigations of OM3-FA dietary supplements show that quantities of EPA and DHA are highly variable within and between brands. Dietary supplements also may contain potentially harmful components, including oxidized OM3-FA, other lipids, cholesterol, and toxins. Prescription OM3-FA products may contain DHA and EPA or EPA alone. All prescription OM3-FA products have demonstrated statistically significant triglyceride reduction as monotherapy or in combination with statins in patients with hypertriglyceridemia. Differential effects between products containing EPA and DHA compared with a high-purity EPA product (icosapent ethyl) have clinical implications: Increases in low-density lipoprotein cholesterol associated with DHA have the potential to confound strategies for managing patients with dyslipidemia. Cardiovascular outcomes studies of prescription CM3-FA products are ongoing. CONCLUSIONS: OM3-FA dietary supplements should not be substituted for prescription products, and prescription OM3-FA products that contain DHA are not equivalent to or interchangeable with high-purity EPA (icosapent ethyl) and should not be substituted for it. PMID- 26882631 TI - Drug spending to reach nearly $600B by 2020. PMID- 26882632 TI - Psychosocial needs assessment post kidney transplant: Feasibility of a post transplant specific support group. AB - This project assessed unmet psychosocial needs of kidney transplant recipients and the feasibility of a support group located at an urban Canadian hospital to meet those needs. A survey assessed transplant recipient concerns about psychosocial issues related to transplantation, interest in a support group, desired group composition, facilitation, leadership, barriers and alternative forms of support. Most respondents were more than two years since transplant and were more concerned about medical complications, returning to normalcy, and had a greater desire to talk to other transplant recipients. Forty per cent of respondents indicated they would be interested in a support group. However, 60% indicated that a support group hosted in the hospital setting would be a deterrent to attending, citing time and transportation as the greatest barriers. More research is needed to assess the feasibility of post-kidney transplant support groups closer to recipients' homes and the feasibility of alternative forms of support. PMID- 26882633 TI - Warfarin for stroke prevention in hemodialysis patients with non-valvular atrial fibrillation. PMID- 26882634 TI - Palliative care in patients with advanced chronic kidney disease. AB - The past five decades have shown a tremendous growth, world wide, in the number of patients with advanced chronic kidney disease (CKD). Patients with advanced CKD today are notably older, have significant comorbidity, substantial symptom burden and, ultimately, have high mortality. Subsequently, there is an increased global awareness of the need to integrate palliative care into routine kidney care to enhance the quality of life and death for patients with advanced CKD. This article outlines a conceptual framework for kidney palliative care for patients with advanced CKD and discusses issues such as symptom burden, illness trajectories, advance care planning, and complex decision-making, including decisions around the appropriate initiation, withholding and withdrawal of dialysis, and the potential palliative care roles and responsibilities for nursing staff within kidney care programs. PMID- 26882635 TI - Depression in patients with chronic kidney disease. AB - Chronic kidney disease affects 10 per cent of the general population. A number of studies over the last decade have established that there is a higher prevalence of depression amongst those with chronic kidney disease (CKD). Biological, psychological and socio-economic factors influence the higher prevalence of depression in this population. The complex interplay between bio-psycho-social factors helps explain the bidirectional relationship between progress of CKD and depression. We summarize the prevalence and etiology of depression in those suffering from CKD and describe in brief the impact of depression in CKD on outcomes such as mortality and morbidity, as well as the different management options that are available. The purpose of this article is to provide a summarized and clinically applicable update on depression for nurses, which will assist them in recognizing and seeking treatment for depression, as well as highlight what is already being done and what needs to be done in terms of recognition and treatment of this common psychiatric condition. PMID- 26882636 TI - Predatory publishing: What editors need to know. PMID- 26882637 TI - The patient perspective--A story of Paired Exchange Renal Transplant. PMID- 26882638 TI - Deprescribing: Is there a role in hemodialysis? PMID- 26882640 TI - Thoughts on National Children's Dental Health Month. PMID- 26882639 TI - Practice innovation: Collaboration with community partners to improve home dialysis safety in the province of Ontario. PMID- 26882641 TI - Watch Out for Objectionable 'Insecurity Clauses' in Practice Loan Documentation. PMID- 26882642 TI - It's My Party and I'll Cry if I Want to! PMID- 26882643 TI - Keep Your Dental Practice Safe from a Cyber Attack. PMID- 26882644 TI - PEDIATRIC DENTISTRY. Focus on Children's Dental Health. PMID- 26882645 TI - Etiology, Classification and Management of Ectopic Eruption of Permanent First Molars. AB - Ectopic eruption of a permanent tooth involves abnormal resorption of a portion or all of the adjacent primary tooth. Among the most commonly ectopically erupted teeth are the permanent first molars. Ectopically erupting molars may require intervention to allow for full eruption, or they may spontaneously self-correct and erupt into occlusion. Decisions regarding the necessity of intervention, its ideal timing, and intervention type are multifactorial. Treatment options for the ectopically erupting permanent first molar include the elastomeric separator, brass wire, pre-fabricated clip separator, custom made appliances (Humphrey appliance, Halterman appliance), or extraction of the primary molar. Early intervention when indicated can ensure proper full eruption of the permanent first molar and prevent mesial angulation, arch perimeter loss, tooth impaction and ankylosis. Two cases are described that manage ectopic eruption of the permanent first molar. PMID- 26882646 TI - Dental Treatment Considerations for Children with Complex Medical Histories: A Case of Townes-Brock Syndrome. AB - It is common for oral health and dental care to be considered a lesser priority for children with complex medical histories than other aspects of their health care. Often, these patients are at a high risk for caries and infection due to poor oral health practices at home, special or restricted diets, and no early establishment of a dental home for routine dental care. Unfortunately, many of these patients present to their first dental visits with caries and require aggressive treatment, such as extractions instead of pulp therapy, or crowns instead of fillings, due to their high caries risk and the difficulty in safely managing them medically during treatment. A unique example of this occurred at the Children's Hospital of Michigan, where a patient with Townes-Brock syndrome (TBS) presented to the dental clinic with advanced caries. TBS is a rare autosomal dominant disorder characterized by major findings such as anomalies of the external ear, imperforate anus, renal malformations, and malformations of the hand. Like many medically complex cases, dental anomalies are not a direct consequence of TBS; however, due to the necessity of high calorie and high sugar feeding supplementation, many of these patients are at high risk for advanced dental caries. Due to this high caries risk, a more aggressive treatment plan is necessary to minimize the risk of recurrent decay and infection. It is critical to stress that even if the disease, syndrome, etc., of a patient does not have inherent dental consequences, it is imperative for regular dental care to be part of the comprehensive treatment plan for these patients. This includes the establishment of a dental home at a young age and proper oral health education of the patient's caregivers and their physicians. In the case of the patient with TBS, recommendations for daily brushing, especially after high sugar feedings was stressed, as well as the reduction of any other sweets within the diet. PMID- 26882647 TI - Do Early Dental Visits Reduce Treatment and Treatment Costs for Children? AB - PURPOSE: The purpose of this paper was to determine if number and cost of dental treatments in high caries-risk children differs in children with early dental intervention compared to children with later intervention. METHODS: Billing data from children age zero to seven years old, whose first dental visit was between January 1, 2004 and December 31, 2004, were collected from 20 corporate treatment centers serving children from lower socioeconomic status backgrounds. Data included age at first visit, dental treatment codes, and associated costs for eight years after the first dental visit. Treatment included restorations, crowns, pulpotomies, and extractions. First visit age was categorized into early starters (younger than four years old) and late starters (four years of age or older). Linear regression with cluster adjustment for clinic determined a difference in costs and dental treatments by early and late starters. RESULTS: Of 42,532 subjects, 17,040 (40 percent) were early starters and 25,492 (60 percent) were late starters. There were 3.58 more dental procedures per- formed on late starters, over eight years of follow-up, than on early starters (P < .001). Late starters spent $360 more over eight years of follow-up than early starters (P < .001). CONCLUSION: In this study, number of procedures per- formed were fewer and cost of treatment less for children seen earlier versus later. PMID- 26882648 TI - Common Barriers to Fnancial Success--And How to Overcome Them. PMID- 26882649 TI - New discharge planning rules focus on preferences, transitions. AB - The Centers for Medicare & Medicaid Services has issued proposed changes to the Medicare Conditions of Participation that would increase the focus on patient preferences in the discharge process and beef up communication when patients are discharged from the hospital. The requirements would be in effect for critical access hospitals, long-term acute care hospitals, and inpatient rehabilitation hospitals in addition to acute care hospitals and would require a discharge plan for patients receiving observation services, patients being released from the emergency department, and patients receiving same-day surgery or procedures that require anesthesia or sedation. The proposed rule requires the discharge plan to include patients' goals and preferences and that the treating physician help create the plan. It includes specific requirements for discharge instructions. A big focus is providing the primary care physician with the discharge summary and other comprehensive information to the patient's primary care physician within 48 hours of discharge and pending test results within 24 hours of their availability. It spells out specific information that should be provided at the time a patient transfers to a post-acute facility or is referred for home health services. PMID- 26882650 TI - Preventing readmissions is a core focus of new discharge planning rules. PMID- 26882651 TI - Diabetes program focuses on the basics. AB - Vidant Medical Center in Greenville, NC, is saving about $425,000 a year by implementing a multidisciplinary model that teaches patients with diabetes the basic skills they need to stay safe after discharge. A multidisciplinary team that included pharmacy, nutrition, nursing, and case management developed the program after data showed that the hospital's traditional diabetes program was reaching only about 20% of the diabetes population. The team determined that patients need four survival skills to stay healthy at home: medications, glucose monitoring, hypoglycemia recognition, and having a relationship with a primary care provider in the community. The team developed a graphic that illustrates what the medical provider, the bedside nurse, the pharmacist, the case manager or social worker, and the nutritionist need to do for all patients with diabetes. Each member of the team also reinforces the four survival skills. PMID- 26882652 TI - Mobile teams fill the gap between the hospital and the community. AB - A clinical team from The Valley Hospital in Ridgewood, NJ, visit at-risk patients at home after discharge if the patients don't qualify for or refuse home health services. A mobile team that includes a paramedic, a critical care nurse, and an emergency medical technician visits patients who have been referred by the case managers after a risk assessment. The team performs a comprehensive assessment of the patients and their home situations and reinforces the discharge teaching they received in the hospital. In most cases, the team makes only one visit but will return if the patient still needs support. PMID- 26882653 TI - TJC praises top hospitals in annual report. PMID- 26882654 TI - Petchienes A-E, Meroterpenoids from Ganoderma petchii. AB - Petchienes A-E (1-5), five new meroterpenoids, were isolated from the fruiting bodies of Ganoderma petchii. Their structures, including absolute configurations, were elucidated by means of spectroscopic and computational methods. Compound 4 was isolated as a racemic mixture, which was finally purified by chiral HPLC to yield individual (-) and (+)-antipodes. Biological evaluation showed that compounds 2 and (-)-4 could increase intracellular free calcium concentration at 10 MUM in HEK-293 cells. PMID- 26882655 TI - Megastigmane Glycosides from the Leaves of Tripterygium wilfordii. AB - Two new megastigmane glycosides, named wilfordonisides A and B (1 and 2), and four known compounds (3-6) were isolated from the leaves of Tripterygium wilfordii, and one new aglycon, named wilfordoninol A (2a), was acquired by enzymatic hydrolysis of 2. The absolute stereostructures of the compounds were determined by Mosher's method and by CD. At a concentration of 10 MUM, compounds 1, 3, and 5 inhibited STAT1 translocation by 38.1 +/- 0.9%, 55.8 +/- 0.8%, and 53.9 +/- 1.0%, respectively. PMID- 26882656 TI - Cytochalasans and Sesquiterpenes from Eutypella scoparia 1-15. AB - Three new compounds, an open-chain cytochalasan scoparasin C (1), a pyrichalasan scoparasin D (2), and a beta-eudesmol type sesquiterpene scopararane C (5), along with three known compounds (3, 4 and 6), were isolated from the marine fungus Eutypella scoparia 1-15. Their structures were determined on the basis of comprehensive NMR and MS analysis. Compound 2 exhibited potent cytotoxicities with very low IC50 values against several cancer cell lines, including A375, A549, HepG2 and MCF-7. PMID- 26882657 TI - Concise Synthesis of Taiwaniaquinol B and 5-epi-Taiwaniaquinone G. AB - The natural product taiwaniaquinol B and the unnatural 5-epi-taiwaniaquinone G were synthesized based on a highly efficient tandem acylation-Nazarov cyclization approach to build the tricyclic skeleton. PMID- 26882658 TI - Effect of Enzyme Inhibitors on Terpene Trilactones Biosynthesis and Gene Expression Profiling in Ginkgo biloba Cultured Cells. AB - The biosynthetic pathway of terpene trilactones of Ginkgo biloba is unclear. In this present study, suspension cultured cells of G. biloba were used to explore the regulation of the mevalonic acid (MVA) and methylerythritol 4-phosphate (MEP) pathways in response to specific enzyme inhibitors (lovastatin and clomazone). The results showed that the biosynthesis of bilobalide was more highly correlated with the MVA pathway, and the biosynthesis of ginkgolides was more highly correlated with the MEP pathway. Meanwhile, according to the results, it could be speculated that bilobalide might be a product of ginkgolide metabolism. PMID- 26882659 TI - Macrocyclic Diterpenoids from the Latex of Euphorbia helioscopia. AB - One new jatrophane diterpenoid, 7alpha,9beta,15beta-triacetoxy-3beta-benzoyloxy 14beta-hydroxyjatropha-5E,11E-diene (3), together with four known macrocyclic diterpenoids, euphoheliosnoid A (1), epieuphoscopin B (2), euphohelioscopin A (4) and euphoscopin C (5), were isolated from the stem latex of Euphorbia helioscopia. Their structures were established by spectroscopic analyses. In the anti-inflammatory assay, euphohelioscopin A (4) exhibited moderate inhibitory activity on the release of cytokine TNF-alpha (IC50 = 23.7 +/- 1.7 MUM), IL-6 (IC50 = 46.1 +/- 1.1 MUM) and chemokine MCP-1 (IC50 = 33.7 +/- 3.8 MUM) in lipopolysaccharide (LPS) induced RAW 264.7 macrophages without notable cytotoxicity (IC50 > 80 MUM). PMID- 26882660 TI - A New Triterpenoid from the Aerial Parts of Agrimonia pilosa. AB - (1S,3R,17R,18R,19R,20R,22R)-1,3,19,22-tetrahydroxy-28-norurs-12-en-2-one (1), along with 5 known triterpenoids (2-6), were isolated from the aerial parts of Agrimonia pilosa Ledeb. Their structures were established based on extensive spectroscopic and MS analysis. The absolute configuration of compound 1 was deduced by circular dichroism (CD). Compound 1 was the first example of a 28 norursene backbone isolated from the genus Agrimonia. Compounds 2-6 were tested for anti-inflammatory activities against RAW 264.7 macrophages. A plausible biosynthetic pathway for compound 1 in A. pilosa was also proposed. PMID- 26882661 TI - Two New 18-Norschiartane-type Schinortriterpenoids from Schisandra lancifolia. AB - Two new 18-norschiartane-type schinortriterpenoids, namely wuwezidilactones Q (1) and R (2) were isolated from the stems of Schisandra lancifolia. Their structures were determined on the basis of extensive spectroscopic analysis. The absolute configurations of the new compounds were further determined by ROESY and an empirical comparison of their experimental ECD spectra with literature. PMID- 26882662 TI - Terpenoids and Steroids from Euphorbia hypericifolia. AB - Two new triterpenoids and two new sterols, named euphyperins A-D (1-4), including an oleanane-type triterpenoid (1), a lupane-type nortriterpenoid (2), and two cholestane-type steroids (3 and 4), along with five known compounds (5-9) were isolated from the twigs and leaves of Euphorbia hypericifolia. Euphyperin B (2) represents a rare lupane-type nortriterpenoid, and euphyperin C (3) is a novel 8,14-secocholestane-type steroid. Euphyperin A (1) exhibited moderate PTP1B inhibitory activity with an IC50 = 17.05 +/- 1.12 MUg/mL. PMID- 26882663 TI - A Fragmentation Study of Six C21 Steroidal Aglycones by Electrospray Ionization Ion-Trap Time-of-Flight Tandem Mass Spectrometry. AB - The fragmentation patterns of six C21 steroidal aglycones, metaplexigenin (1), caudatin (2), qingyangshengenin (3), penupogenin (4), 20-cinnamoylsarcostin (5), and gagamine (6), were analyzed by high-resolution electrospray ionization ion trap time-of-flight tandem mass spectrometry (HR-ESI-IT-TOF-MS(n)). The [M-H]+ ions of steroids 1-3 that contain a carbonyl functional group at C-20 (Type I) and [M+H]+ ions of steroids 5-6 that possess a hydroxyl group at C-20 (Type II) were readily observed in MS analyses. The fragmentation pathways and diagnostic fragment ions for these six steroidal aglycones were proposed on the basis of their MS(n) analyses. The common fragmentation pathways for type I steroidal aglycones include the neutral loss of the ester group at C-12 and the hydroxyl moieties on the steroid skeleton, as well as the cleavage of ring D. Their diagnostic fragment ions were identified as m/z 361(B), 343 (C), 325 (D), 307 (F), 283 (G), 259 (E), and 243 (H). The fragmentation behavior of penupogenin (4) in type II was similar to those of type I, with m/z 363 (B'), 345 (C'), 327 (D'), 309 (F'), 283 (G), and 243 (H) as its diagnostic fragment ions. The ester group at C-20 was difficult to cleave in the MS(n) analyses of 20-cinnamoylsarcostin (5) and gagamine (6) so that the loss of this ester group was slower than that at C-12 and hydroxyl groups; the key ions at m/z 329 (I), 311 (J), 293 (K), and 275 (L) were characteristic for 5 and 6. The base ion peaks were derived from the loss of the substituent group at either C-12 or C-17 for both type I and type II steroidal aglycones. PMID- 26882664 TI - Three New Cytotoxic Withanolides from the Chinese Folk Medicine Physalis angulata. AB - Physagulides M-O, three new withanolides (1-3), were isolated from the aerial parts of Physalis angulata L. Their structures were elucidated through extensive spectroscopic techniques, including 1D and 2D NMR, and HRESIMS. The absolute configurations (22-R) of these new compounds were determined by CD analysis. Compounds 1 and 3 showed significant selective cytotoxic activities on the MG-63 cell line, with IC50 values of 4.28 and 5.44 MUM, respectively. PMID- 26882665 TI - Diterpenoid Alkaloids from Aconitum soongaricum var. pubescens. AB - One new diterpenoid alkaloid, pubescensine (1), along with nine known diterpenoid alkaloids (2-10) were isolated from the roots of Aconitum soongaricum var. pubescens. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. All the compounds were evaluated for their antifeedant activities. The aconitine-type diterpenoid alkaloids (1-6) showed considerably potent antifeedant activity (EC50 < 1 mg/cm2), while the activities of napelline-type diterpenoid alkaloids (compds. 7, 9 and 10) were not significant (EC50 > 50 mg/cm2). PMID- 26882666 TI - Two New C18-Diterpenoid Alkaloids from Delphinium anthriscifolium. AB - Two new C18-diterpenoid alkaloids, anthriscifoltine A (1) and anthriscifoltine B (2), along with three known diterpenoid alkaloids, deoxydelcorine (3), anthriscifolcine A (4) and anthriscifolcine G (5), were isolated from the whole herbs of Delphinium anthriscifolium var. majus. Their structures were elucidated by spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS. PMID- 26882667 TI - Majusine D: A New C19-diterpenoid Alkaloid from Delphinium majus. AB - A new C19-diterpenoid alkaloid, designated as majusine D (1), has been isolated from Delphinium majus W. T. Wang. The structure was elucidated by detailed NMR spectroscopic studies. PMID- 26882668 TI - Epoxide Opening of a 7,17-Seco-7,8-Epoxy-C19-Diterpenoid Alkaloid. AB - A new and effective approach toward epoxide opening of a 7,17-seco-7,8-epoxy-C19 diterpenoid alkaloid is herein described. The starting epoxide was prepared from naturally occurring yunnaconitine via a nine-step transformation. Treatment of this epoxide with trifluoroacetic anhydride in dioxane at 110 degrees C followed by reduction with sodium boron hydride generated two epoxide opening compounds 7 and 8. Each of their structures is characteristic of a Delta8,15 bridgehead double bond and a 7beta-oxygen-substituted group. PMID- 26882669 TI - Further Studies on Structure-Cardiac Activity Relationships of Diterpenoid Alkaloids. AB - The cardiac effect of thirty-eight diterpenoid alkaloids was evaluated on the isolated bullfrog heart model. Among them, twelve compounds exhibited appreciable cardiac activity, with compounds 3 and 35 being more active than the reference drug lanatoside. The structure-cardiac activity relationships of the diterpenoid alkaloids were summarized based on our present and previous studies [2]: i) 1alpha-OMe or 1alpha-OH, 8-OH, 14-OH, and NH (or NMe) are key structural features important for the cardiac effect of the aconitine-type C19-diterpenoid alkaloids without any esters. C18-diterpenoid alkaloids, lycoctonine-type C19-diterpenoid alkaloids, and the veatchine- and denudatine-type C20-diterpenoid alkaloids did not show any cardiac activity; ii) the presence of 3alpha-OH is beneficial to the cardiac activity; iii) the effect on the cardiac action of 6alpha-OMe, 13-OH, 15alpha-OH, and 16-demethoxy or a double bond between C-15 and C-16 depends on the substituent pattern on the nitrogen atom. PMID- 26882670 TI - Monoterpenoid Indole Alkaloids from Catharanthus roseus Cultivated in Yunnan. AB - A new monoterpenoid indole alkaloid, 15,20-dehydro-3alpha-(2-oxopropyl) coronaridine (1), along with sixteen analogues (2-17) were isolated from the leaves of Catharanthus roseus cultivated in Yunnan. The new alkaloid was elucidated on the basis of extensive spectroscopic analysis, and the known alkaloids were identified by comparison with the reported spectroscopic data. Among them, alkaloid 16 was isolated from Catharanthus for the first time. PMID- 26882671 TI - Two New Oxindole Alkaloid Glycosides from the Leaves of Nauclea officinalis. AB - Two new oxindole alkaloid glycosides, nauclealomide A and (3S,7R)-javaniside, were isolated from the leaves of Nauclea officinalis. Their structures and absolute configurations were elucidated by means of NMR, HRESIMS, X-ray diffraction, acid hydrolysis and quantum chemical CD calculation. Nauclealomide A is a novel monoterpenoid oxindole alkaloid possessing a rare tetrahydro-2H-1,3 oxazine ring. PMID- 26882672 TI - Lycopodium Alkaloids from Diphasiastrum complanatum. AB - One new lycopodine-type Lycopodium alkaloid, dehydroisofawcettiine N-oxide (1) and eleven known analogues (2-12) were isolated from the whole plant of Diphasiastrum complanatum. The new structure was established on the basis of spectroscopic methods, including 2D NMR techniques. The absolute configurations of 2 and its new N-oxide derivative (1) were deduced by chemical transformation combined with Cotton effects in their electronic circular dichroism (ECD) spectra. PMID- 26882673 TI - Effects of Adding Vindoline and MeJA on Production of Vincristine and Vinblastine, and Transcription of their Biosynthetic Genes in the Cultured CMCs of Catharanthus roseus. AB - Vincristine and vinblastine were found by Liquid Chromatography-Mass Spectrometry (LC-MS) in Catharanthus roseuscambial meristem cells (CMCs) jointly treated with 0.25 mM vindoline and methyl jasmonate (MeJA), suggesting that C. roseus CMCs contain a complete set of the enzymes which are in response to convert vindoline into vincristine and vinblastine. Based on the facts that the transcript levels of vindoline-biosynthetic genes (STR, SGD and D4H) were up-regulated instead of being down-regulated by adding itself to the culture, and that the transcriptional factor ORCA3 was up-regulated simultaneously, we further confirmed that the transcription of STR, SGD, D4H was manipulated by ORCA3. PMID- 26882674 TI - Structures and Chemotaxonomic Significance of Stemona Alkaloids from Stemona japonica. AB - A pair of new alkaloid stereo-isomers, stemocochinin (1) and isostemocochinin (2), was obtained from the roots of Stemona japonica Miq., along with seven known alkaloids, stemonamine (3), isostemonamine (4), maistemonine (5), isomaistemonine (6), croomine (7), stemonine (8), and protostemonine (9). The complete structure and stereochemistry of the pair of isomers were established by extensive analysis of the spectral data. Furthermore, our results indicated that S. japonica is chemically closer to S. sessilifolia than S. tuberosa, which are consistent with our previous DNA study on Stemona species. PMID- 26882675 TI - Chemical Constituents of Euonymus glabra. AB - One new phenolic compound (1) and one new flavan (2), together with eight known compounds (3-10) were isolated from the stems and twigs of Euonymus glabra Roxb. Their structures were elucidated mainly on the basis of 1D and 2D spectroscopic methods and circular dichroism analysis. In addition, compounds 1-10 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Compounds 1-5 and 7 exhibited moderate inhibitory activities with IC50 values ranged from 5.1 to 11.9 MUM. PMID- 26882676 TI - Isoprenylated Flavonoids with PTP1B Inhibition from Ficus tikoua. AB - Two new isoprenylated flavanones, ficustikousins A and B (1 and 2), together with seven known compounds (3-9) were isolated from the whole plant of Ficus tikoua (Moraceae). The structures of the new compounds were elucidated on the basis of spectroscopic methods. Compounds 1-7 exhibited moderate inhibitory activities against PTP1B in vitro. PMID- 26882677 TI - Phenolic Derivatives from Hypericum japonicum. AB - Three new acylphloroglucinol glycosides, hypericumols A - C, together with fifteen known phenolic derivatives, were isolated from the total phenolic extract of Hypericum japonicum. Hypericumols A, B, and C were characterized as 4,6 dimethyl-2-methylpropanoylphloroglucinol-1-O-beta-D-glucopyranoside (1), 4-methyl 2-methylpropanoylphloroglucinol-1-O-beta-D-glucopyranoside (2), and (2'S)-4,6 dimethyl-2-methylbutyrylphloroglucinol-1-O-beta-D-glucopyranoside (3), respectively, on the basis of spectroscopic data interpretation and chemical degradation reaction. PMID- 26882678 TI - Synthesis and Anti-Proliferative Effects of Quercetin Derivatives. AB - Prostate cancer is the most common diagnosed invasive cancer in American men and is the second leading cause of cancer-related deaths. Although there are several therapies successful in treating early, localized stage prostate cancer, current treatment of advanced metastatic castration-resistant prostate cancer remains ineffective due to inevitable progression of resistance to first-line treatment with docetaxel. The natural product quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid compound ubiquitous in dietary plants, possesses evidenced potential in treating advanced metastatic castration-resistant prostate cancer. However, its poor bioavailability and moderate potency hinder its advancement into clinical therapy. In order to engineer quercetin derivatives with improved potency and pharmacokinetic profiles for the treatment of advanced metastatic prostate cancer, we started this study with creating a small library of alkylated derivatives of quercetin for in vitro evaluation. The biological data and chemical reactivity of quercetin and its derivatives reported in literature directed us to design 3,4',7-O-trialkylquercetins as our first batch of targets. Consequently, nine 3,4',7-O-trialkylquercetins, together with four 3,7-O- dialkylquercetins, four 3,3',4',7-tetraalkylquercetins, and one 3,3',4'-O trialkylquercetin, were prepared by one step O-alkylation of commercially available quercetin mediated by potassium carbonate. Their structures were determined by ID and 2D NMR data, and HRMS. Their anti-proliferative activities towards both androgen-refractory and androgen-sensitive prostate cancer cells were evaluated using WST-1 cell proliferation assay. The acquired structure activity relationships indicate that 3,7-O-dialkylquercetins rather than 3,4',7-O trialkylquercetins were much more potent than quercetin towards prostate cancer cells. PMID- 26882679 TI - Compounds with Antifouling Activities from the Roots of Notopterygium franchetii. AB - In antifouling screening, the extract of Notopterygium franchetii de Boiss showed obvious activity. Two new phenylpropanoids (1-2) and five known coumarins (3-7) were isolated from the methanol extract of the roots of this species. The structures of the isolated compounds were determined on the basis of spectroscopic analysis. Compounds 1-2 showed definite antifouling activity against larval settlement of Bugula neritina. PMID- 26882680 TI - New Isochromane Derivatives from the Mangrove Fungus Aspergillus ustus 094102. AB - Four new isochromane derivatives (1-4) along with the known peniciphenol (5) and (R)-2-(hydroxymethyl)-3-(2-hydroxypropyl)pheno (6) were isolated from the EtOAc extract of the fermentation broth of the mangrove fungus, Aspergillus ustus 094102. The structures of the new compounds including the absolute configuration were elucidated on the basis of spectroscopic analysis, CD and ECD calculation. Compounds 1 and 2 exhibited alpha-glucosidase inhibition and anti-oxidation against DPPH radical with IC50 values of 1.4 mM and 25.7 MUM, respectively. PMID- 26882681 TI - Pericocins A-D, New Bioactive Compounds from Periconia sp. AB - One new dihydroisocoumarin, pericocin A (1), one new chromone, pericocin B (2), and two new alpha-pyrone derivatives, pericocins C-D (3-4), together with two known compounds, 3-(2-oxo-2H-pyran-6-yl)propanoic acid (5) and (E)-3-(2-oxo-2H pyran-6-yl)acrylic acid (6), were isolated from the culture of the endolichenic fungus Periconia sp.. Their structures were elucidated by spectroscopic methods. All these compounds are derived from the polyketone biosynthetic pathway. Compound 1 was obtained as a mixture of enantiomers. The antimicrobial activity of compounds 1-5 was tested against Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans. Compounds 1-5 showed moderate antimicrobial activity against A. niger and weak activity against C. albicans. PMID- 26882682 TI - New Benzenoids from the Roots of Lindera aggregata. AB - Two new benzenoids, linderagatin A and B (1-2), were isolated from the roots of Lindera aggregata. Their structures were elucidated on the basis of 1D (1H, 13C) and 2D NMR (COSY, NOESY, HSQC and HMBC) spectra. Moreover, their absolute configurations were established from ECD spectra compared with previous reports. PMID- 26882683 TI - 12-Membered Resorcylic Acid Lactones Isolated from Saccharicola bicolor, an Endophytic Fungi from Bergenia purpurascens. AB - Two new resorcylic acid lactones, 13-hydroxyhidroresorcylide (1) and 12 hydroxyhidroresorcylide (2), along with four known congeners (3-6) were isolated from Saccharicola bicolor, an endophytic fungus from Bergenia purpurascens. Their structures were elucidated by interpretation of the spectroscopic evidence. PMID- 26882684 TI - Phenylpropanoid Glycosides from the Leaves of Ananas comosus. AB - Two new phenylpropanoid glycosides, named beta-D-(1-O-acetyl-3,6-O-diferuloyl) fructofuranosyl beta-D-6'-O-acetylglucopyranoside (1) and beta-D-(1-O-acetyl-3,6 O-diferuloyl) fructofuranosyl alpha-D-glucopyranoside (2), along with two known analogues (3-4) and four glycerides (5-8), were isolated from the EtOAc extract of the leaves of Ananas comosus. Their structures were elucidated on the basis of 1D- and 2D-NMR analyses, as well as HR-ESI-MS experiments. Compounds 1-4 showed significant antibacterial activities against Staphylococcus aureus and Escherichia coli. PMID- 26882685 TI - Tannins and Antioxidant Activities of the Walnut (Juglans regia) Pellicle. AB - The total phenolic content and antioxidant activities of the acetone extract and derived fractions from the walnut (Juglans regia) pellicle were estimated. The BuOH fraction exhibited the strongest antioxidant activity with the highest phenolic content. A phytochemical investigation of this fraction led to the isolation of three tannins, 2,3-hexahydroxydiphenoylglucose (1), pedunculagin (2) and 2,3,4,6-tetragalloylglucose (3). Pedunculagin showed high content and powerful activity, which implied that this compound plays an important role in the antioxidant activity of the walnut pellicle. PMID- 26882686 TI - Chemical Constituents of Cordyceps cicadae. AB - One new bifuran derivative (1), together with fourteen known compounds, were isolated from Cordyceps cicadae X. Q. Shing. The known compounds included nine nucleosides, uracil (2), uridine (3), 2'-deoxyuridine (4), 2'-deoxyinosine (5), guanosine (6), 2'-deoxyguanosine (7), thymidine (8), adenosine (9), and 2' deoxyadenosine (10); three amino acids tryptophan (11), phenylalanine (12), and tyrosine (13); and two dopamine analogues N-acetylnoradrenaline (14) and its dimer, trans-2-(3',4'-dihydroxyphenyl)-3-acetylamino-7-(N-acetyl-2"-amino ethylene)-1,4-benzodioxane (15). Their structures were decisively elucidated by spectroscopic analysis, including 1D and 2D NMR techniques. PMID- 26882687 TI - A New Bithiophene from the Root of Echinops grijsii. AB - A new bithiophene, 5-(4-hydroxy-3-methoxy-1-butyny)-2,2'-bithiophene (1), and sixteen known thiophenes: 2-(3,4-dihydroxybut-1-ynyl)-5-(penta-1,3 diynyl)thiophene (2), alpha-terthienyl (3), 5-(3,4-dihydroxybut-1-ynyl)-2,2' bithiophene (4), 5-acetyl-2,2'-bithiophene (5), 5-formyl-2,2'-bithiophene (6), methyl 2,2'-bithiophene-5-carboxylate (7), 5-(but-3-en-1-ynyl)-2,2'-bithiophene (8), 5-(4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (9), cardopatine (10), isocardopatine (11), 5-(3-hydroxy-4-isovaleroyloxybut-1-ynyl)-2,2'-bithiophene (12), 5-(3-hydroxymethyl-3-isovaleroyloxyprop-1-ynyl)-2,2'-bithiophene (13), 5-(4 hydroxy-1-butynyl)-2,2'-bithiophene (14), 5-(4-acetoxy-1-butynl)-2,2'-bithiophene (15), 2,2'-bithiophene-5-carboxylic acid (16) and 2-(4-hydroxybut-1-ynyl)-5 (penta-1,3-diynyl)thiophene (17) were isolated from the roots of Echinops grjisii Hance. Among them, compounds 6, 7 and 16 were isolated from a natural source for the first time. Compounds 2, 4 and 14 exhibited significant anti-inflammatory activity against nitrite of LPS-stimulated production in the RAW 264.7 cell line. PMID- 26882688 TI - Cyclic Lipopeptides with Herbicidal and Insecticidal Activities Produced by Bacillus clausii DTM1. AB - Seven cyclic lipopeptide biosurfactants (1-7) were isolated for the first time from the fermentation broth of endophytic Bacillus clausii DTM1 and were identified as anteisoC13[Val7] surfactin-(L-Glu)-O-methyl-ester (1), anteisoC12[Val7] surfactin (2), anteisoC15[Val7] surfactin (3), isoC14[Leu7] surfactin (4), anteisoC12[Leu7] surfactin (5), nC13[Leu7] surfactin (6), and anteisoC14[Leu7] surfactin-(L-Glu)-O-methyl-ester (7); 1 has not been isolated before as a natural product from any source. Plate-based herbicide and insecticide bioassays showed that all compounds exhibited interesting insecticidal and herbicidal activities. PMID- 26882689 TI - Synthesis of (6R,12R)-6,12-Dimethylpentadecan-2-one, the Female-Produced Sex Pheromone from Banded Cucumber Beetle Diabrotica balteata, Based on a Chiron Approach. AB - Herein we describe a synthesis of (6R,12R)-6,12-dimethylpentadecan-2-one (5), the female produced sex pheromone of banded cucumber beetle Diabrotica balteata Le Conte, from (R)-4-methyl-5-valerolactone, a methyl-branched chiron. PMID- 26882690 TI - A Rapid Study of Botanical Drug-Drug Interaction with Protein by Re-ligand Fishing using Human Serum Albumin-Functionalized Magnetic Nanoparticles. AB - A great many active constituents of botanical drugs bind to human serum albumin (HSA) reversibly with a dynamic balance between the free- and bound-forms in blood. The curative or side effect of a drug depends on its free-form level, which is always influenced by other drugs, combined dosed or multi-constituents of botanical drugs. This paper presented a rapid and convenient methodology to investigate the drug-drug interactions with HSA. The interaction of two steroidal saponins, dioscin and pseudo-protodioscin, from a botanical drug was studied for their equilibrium time and equilibrium amount by re-ligand fishing using HSA functionalized magnetic nanoparticles. A clear competitive situation was obtained by this method. The equilibrium was reached soon about 15 s at a ratio of 0.44: 1. Furthermore, the interaction of pseudo-protodioscin to total steroidal saponins from DAXXK was also studied. The operation procedures of this method were faster and more convenient compared with other methods reported. PMID- 26882691 TI - Serum Metabolomic Profiling of Rats by Intervention of Aconitum soongaricum. AB - To understand the toxic mechanism and to find the changes in the endogenous metabolites of Aconitum soongaricum Stapf for clinical detection, a combination of 1H NMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the blood serum samples collected from the rat model. In total, thirteen biomarkers of A. soongaricum were found and identified. It turned out that A. soongaricum treatment may partially disorder the metabolism. The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the toxicity caused by A. soongaricum. PMID- 26882692 TI - Re-evaluation of ABTS*+ Assay for Total Antioxidant Capacity of Natural Products. AB - 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS*+) is a stable free radical frequently used for estimating the total antioxidant capacity (TAC) of natural products. The existing methods for ABTS*+ radical-scavenging activity assays are diverse in pre-diluting solvents and reaction time, which lead to errors in the TAC estimations. To develop an effective and universal method for estimating the ABTS*+ capacity accurately and reasonably, five pre-dilution solvents [methanol, ethanol, phosphate buffer (Na2HPO4-NaH2PO4, 200 mM, pH = 7.4), PBS buffer (Na2HPO4-NaH2PO4- NaCl, 200 mM, pH = 7.4), and distilled water] and different reaction times were investigated in ABTS*+ assays of five typical antioxidants. The results showed that the solvent effects were very significant. When using different pre-diluting solvents, different detection wavelengths should be selected. ABTS*+ assay could be measured within 2-10 min to obtain a rough result, which was mostly 6 min in the literature. However, full and accurate evaluation of antioxidant reactivity rather than capacity requires recording ABTS*+ loss continuously during the whole reaction period. The present study makes a recommendation for estimating the ABTS*+ capacity accurately and reasonably. PMID- 26882693 TI - Chemical Synthesis of the Echinopine Sesquiterpenoids. AB - As new members of the sesquiterpenoid family, echinopines A and B were found to possess an unprecedented [3/5/5/7] carbon framework, which has stimulated considerable interest among the chemistry community since their isolation. This review article documents chronologically the steps towards chemical synthesis of the echinopine sesquiterpenoids, showcasing different strategies by resorting to the toolkit of organic chemistry. PMID- 26882694 TI - Synergistic Effects of Dietary Natural Products as Anti-Prostate Cancer Agents. AB - This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer. PMID- 26882695 TI - Ligustrum lucidum and its Constituents: A Mini-Review on the Anti-Osteoporosis Potential. AB - Osteoporosis is a metabolic bone disorder commonly occurred in aging populations, particularly postmenopausal women and patients who undergo long-term steroid or anti-estrogen therapies. Given the rapid growth of the aging population, the prevalence of bone loss, and the huge medical and healthcare cost involved, demand for alternative approaches for the promotion of bone health is pressing. With the advent of global interest in complementary and alternative medicine and natural products, Chinese medicine serves as a viable source that offers benefits to improve and maintain bone health. This review summarizes the scientific information on the Chinese medicinal herb Ligustrum lucidum and its chemical components as potential therapy for osteoporosis. PMID- 26882696 TI - Alice, Benzene, and Coffee: The ABCs of Ecopharmacognosy. AB - The sesquicentennial celebrations of the publication of "Alice's Adventures in Wonderland" and the structure of benzene offer a unique opportunity to develop a contemporary interpretation of aspects of Alice's adventures, illuminate the symbolism of benzene, and contextualize both with the globalization of coffee, transitioning to how the philosophy and sustainable practices of ecopharmacognosy may be applied to modulating approaches to the quality, safety, efficacy, and consistency (QSEC) of traditional medicines and dietary supplements through technology integration, thereby improving patient-centered health care. PMID- 26882697 TI - [Greetings of the Special Issue for 109th Japanese Society of Medical Physics Annual Meeting]. PMID- 26882698 TI - [The Project Intention and a Report on the JSMP109 Symposium 1]. PMID- 26882699 TI - [IAEA Training Course Series TCS-37 Clinical Training of Medical Physicists Specializing in Radiation Oncology]. AB - Training program IAEA TCS-37 (Training course series No.37) "Clinical Training of Medical Physicists Specializing in Radiation Oncology (2009)" was fixed to practical training syllabus at faculty and graduate course of medical physics of a university. TCS-47 for diagnostic radiology (2010) and TCS-50 for nuclear medicine (2011) were also involved in the syllabus. These training courses had been developed by IAEA RCA RAS6038 project since 2002. In this paper, first, comparison with other training programs in the world was made in terms of (1) Degree of extent of subject or field, (2) Concreteness or specificity, (3) Degree of completion, (4) Method of certification and (5) Practicability. IAEA TCS series got the most points among ten programs such as EMERALD/EMIT, AAPM rpt.No.90 and CAMPEP accredited programs. Second, TCS-37, TCS47 and TCS50 were broken down to 6, 5 and 6 subjects of training course respectively. Third, each subject was further broken down to 15 times of training schedule where every time was composed by 3 hours of training. Totally 45 hours of a subject were assigned to one semester for getting one unit of credit. Seventeen units should be credited up to three years in graduate course to finish the whole program. PMID- 26882700 TI - [Medical Physics Residency Program at University of Tsukuba]. PMID- 26882701 TI - [Medical Physics Clinical Training at Osaka University]. PMID- 26882702 TI - [A Report on the JSMP 109 Symposium 2 "How Could We Contribute in Reducing the Lung Cancer Mortality?: Facing to CMS Decision for Lung Cancer with Low Dose CT Screening"]. PMID- 26882703 TI - [Current Situation and Perspective of CT Lung Cancer Screening: Trials in Hiroshima Prefecture]. PMID- 26882704 TI - [A Decrease in Lung Cancer Mortality Following the Implementation of CT Screening for General Population]. AB - In Hitachi Medical Area, a large-scale lung cancer screening program using low dose CT has been underway in two medical facilities since its introduction in 1998 and 2001. A total of 61,914 tests were performed among 25,385 participants until 2006. Two hundred and ten lung cancer patients had been identified on CT screening. The estimated 5-year survival rate for all patients was 90%. Among residents in Hitachi City, nearly 40% of inhabitants aged 50-69 years were estimated to have participated in the screening from 1998 through 2009. Cancer mortality data were obtained from a regional cancer registry and the standardized mortality ratio (SMR) of lung cancer was calculated for each 5-year period during 1995-2009. For residents aged 50-79 years, SMR was nearly unity between 1995 and 2004; however, there was a significant decrease during 2005-2009, with SMR (95% confidence interval) being 0.76 (0.67-0.86). These results suggest that the wide implementation of CT screening may reduce lung cancer mortality in the community, 4-8 years after introduction. It is desirable to continue to focus on future developments, including original research in Japan. PMID- 26882705 TI - [Current Status and Future Perspectives of CAD system in Lung Cancer CT Screening]. AB - Current status of the developments of computer-aided detection/diagnosis (CAD) system for lung cancer screening with CT imaging is reviewed along with the commercialization status. Issues to be solved for the lung CAD popularization and QA for CAD are also described followed by the future perspectives of the CAD. PMID- 26882707 TI - [Series: Fundamental Electromagnetics for Beginners (3)]. PMID- 26882706 TI - [Reduction of Lung Cancer Mortality by Disseminating CT Screening: Contribution from Medical Physics]. PMID- 26882708 TI - [Medical Applications of the PHITS Code I: Recent Improvements and Biological Dose Estimation Model]. AB - PHITS is a general purpose Monte Carlo particle transport simulation code developed through the collaboration of several institutes mainly in Japan. It can analyze the motion of nearly all radiations over wide energy ranges in 3 dimensional matters. It has been used for various applications including medical physics. This paper reviews the recent improvements of the code, together with the biological dose estimation method developed on the basis of the microdosimetric function implemented in PHITS. PMID- 26882709 TI - UnitedHealth alone so far in threatening to exit exchanges. PMID- 26882711 TI - CMS' 'doc fix' may need some repairs itself. PMID- 26882710 TI - Bundled-payment demo has nursing homes seeing stars. PMID- 26882712 TI - Joint Commission to shelve hospital Top Performer program until 2017. PMID- 26882713 TI - U.S. hospitals take different approach than the French in planning for mass casualties. PMID- 26882714 TI - Taking a broader view of health. With less need for charity care, hospitals focus on community health improvement. PMID- 26882715 TI - Whistle-blower worries. Hospitals likely to see more False Claims suits tied to doc-compensation deals. PMID- 26882717 TI - Strengthen palliative care to help build a more patient-centered system. PMID- 26882716 TI - A cloudy dawn for biosimilars. PMID- 26882718 TI - Urban hospitals boost local hiring. PMID- 26882719 TI - Politicians' ACA stance depends on how close they are to the point of service. PMID- 26882720 TI - Largest skilled-nursing providers. Ranked by net revenue. PMID- 26882721 TI - A WAY FORWARD FOR THE NHS. Take a place-based approach to care. PMID- 26882723 TI - FOCUS SHOULD BE ON PREVENTION. PMID- 26882722 TI - ON CHANGING THE CULTURE OF BULLYING IN THE NHS. PMID- 26882724 TI - How to read the 2015 HSJ100. PMID- 26882725 TI - WORKFORCE. Developing new model workers. PMID- 26882726 TI - Delivering-change. DAWN OF THE VOLUNTEER REVOLUTION. PMID- 26882727 TI - TECHNOLOGY. HOW TO SPOT A GOOD APP. PMID- 26882729 TI - ASSET MANAGEMENT. SCANNING FOR SAVINGS. PMID- 26882728 TI - FINANCE. The real agency spend revealed. PMID- 26882730 TI - Go back and predict the future. PMID- 26882731 TI - Healthcare leaders back feds stepping in to restrain drug prices. PMID- 26882732 TI - States prodded on network rules. PMID- 26882733 TI - Competition heats up for patient-generated health data. PMID- 26882734 TI - Latest budget deal escalates false claims and civil monetary penalties. PMID- 26882735 TI - Prescribing a climate remedy. Healthcare leaders aim to influence international climate change negotiations. PMID- 26882736 TI - Cancer competition. As local treatment centers grow, hospitals look for ways to advertise their superiority. PMID- 26882737 TI - The need for better evidence in treating heart disease. PMID- 26882738 TI - Choice Act lets veterans get comprehensive care at community health centers. PMID- 26882739 TI - Launching a cybersecurity war room. PMID- 26882740 TI - Shared savings don't go far enough in accepting risk. PMID- 26882741 TI - Largest rehabilitation providers. Ranked by net revenue. PMID- 26882742 TI - PARTNERS in excellence. PMID- 26882743 TI - It's all about the PATIENT. PMID- 26882744 TI - Converging infrastructure systems. PMID- 26882745 TI - Lab results. PMID- 26882747 TI - A customer-centric approach to environmental services. PMID- 26882746 TI - Achieving stable power. PMID- 26882748 TI - Transitioning to a BIM platform. PMID- 26882749 TI - Mental health patients need affordable, nutritious food too. PMID- 26882750 TI - Choosing to work in aged care. PMID- 26882751 TI - Support for the AT role. PMID- 26882753 TI - Reporting substandard care. PMID- 26882752 TI - Seeking study volunteers. PMID- 26882754 TI - Free care in the Pacific. PMID- 26882755 TI - Diagnosing lesions and preventing skin cancer. PMID- 26882756 TI - Appreciating the gift of a new liver. PMID- 26882757 TI - Teaching health in South Sudan. PMID- 26882758 TI - Obstetric fistula--the untreated tragedy. PMID- 26882759 TI - The power of kindness. Acts of kindness by nurses live long in patients' memories. PMID- 26882760 TI - Resting easy in sleep. PMID- 26882761 TI - Cultural understanding crucial in Bougainville. PMID- 26882762 TI - Schools need good-quality toilets. PMID- 26882763 TI - Career planning useful for older nurses. PMID- 26882764 TI - The forgotten 'sisters' of WW1. PMID- 26882765 TI - Imagine what we could do! PMID- 26882766 TI - Shining a light on nursing. PMID- 26882767 TI - A big year for aged care. PMID- 26882768 TI - Advocating for the health of whanau. PMID- 26882769 TI - Respiratory nursing: Addressing inequality is the key to health. PMID- 26882770 TI - Emergency nurses: Asking for help important. PMID- 26882771 TI - Neonatal nursing: Shaping a positive journey for patients. PMID- 26882773 TI - Sedentary behaviour is bad for your mental health. PMID- 26882772 TI - Nurse managers: Creating healthy workplaces. PMID- 26882774 TI - Diagnosis and management of osteoporosis. AB - Osteoporosis is a common condition characterised by low bone mineral density (BMD) and an increased risk of fragility fractures. It affects up to 30% of women and 12% of men at some point in their lives. Two of the most important risk factors are increasing age and female gender, although other common and potentially modifiable risk factors include long-term corticosteroid therapy, chronic inflammatory disease, malabsorption and untreated premature menopause. The diagnosis of osteoporosis can be confirmed by DEXA but this should only be performed in patients who have an increased risk of fracture on the basis of clinical risk factors. DEXA should be considered if the 10-year risk of major osteoporotic fracture is > 10%. If the BMD T-score values by DEXA at the lumbar spine, femoral neck or total hip are at or below -2.5 then the diagnosis of osteoporosis is confirmed. Vertebral fractures are generally taken as diagnostic of osteoporosis, even if spine BMD values are not in the osteoporotic range. Oral bisphosphonates are the first-line treatment. If they are contraindicated or not tolerated then parenteral therapy should be considered. There is evidence that fractures occur in glucocorticoid-induced osteoporosis at higher levels of BMD than in postmenopausal osteoporosis so therapy should be considered in patients with a BMD T-score of <-1.5. Although it is useful to have a DEXA scan before starting treatment to provide a baseline value to assess response, this investigation is not absolutely necessary to initiate bone protective therapy, especially in those aged above 65 since the vast majority of these patients will have a T-score of -1.5 or below. In younger individuals where BMD is likely to be higher DEXA is useful in determining if bone protective treatment is needed immediately or if it could be delayed until the T score falls below -1.5. PMID- 26882775 TI - Evaluating the patient with low back pain. AB - In the UK, low back pain is the most common cause of disability in young adults and every year 6-9% of adults consult their GP about back pain. A thorough history and examination is required to exclude an alternative diagnosis, such as pain arising from the hip or trochanteric bursa and to categorise patients as having: serious spinal pathology, nerve root/radicular pain or non-specific back pain. Inflammatory back pain is often missed, particularly in the early stages when examination may be normal. The primary features are pain arising in patients under 40, thoracolumbar or sacroiliac pain and alternating buttock pain. Stiffness in the early morning and after rest is a hallmark of inflammatory back pain. There may also be peripheral joint involvement with evidence of inflammatory arthritis as well as extra-articular manifestations such as iritis, psoriasis and colitis. Sphincter disturbance leading to loss of bladder or bowel control should also be explored as it is a sign of spinal cord compression or cauda equina syndrome. Both of these are neurosurgical emergencies and need urgent referral for further investigation and possible intervention. The majority of patients with low back pain can be managed in primary care as the pain will usually be self-limiting. Patients with suspected inflammatory back pain should be referred to rheumatology as soon as possible in order to institute early management and prevent long-term deformity and disability. Patients with suspected serious spinal pathology should be referred urgently for further investigation. Red flag symptoms should raise concerns regarding a possible sinister cause such as malignancy and more than one red flag mandates urgent further investigation. PMID- 26882776 TI - The case of the migrating IUD. AB - A 30-year-old lady presented to the gynaecologist with persistent vaginal bleeding following insertion of an IUD. At the time, abdominal examination was unremarkable and speculum examination revealed normal external genitalia and cervix. A transvaginal ultrasound showed a normal uterus, normal ovaries and no adnexal masses or free fluid. It was assumed that the IUD had fallen out. Around the same time she presented to her GP with a short history of dysuria, intermittent visible haematuria and recurrent urinary tract infections. After initial management in general practice for 12 months, she was referred to the urology department for further investigation. She underwent flexible cystoscopy, which showed the presence of an IUD within the bladder. Under general anaesthesia, it was found that the body of the IUD had penetrated the bladder mucosa and become embedded in the right lateral wall of the bladder. The IUD was markedly calcified but was easily removed endoscopically as a whole unit with grasping forceps. A three-week postoperative cystogram ruled out the presence of a fistula. At the six-week postoperative review she was asymptomatic and well. PMID- 26882777 TI - MIGRAINE AND OCULAR DEFECTS. PMID- 26882778 TI - A tale of the unexpected. PMID- 26882779 TI - THE USE OF TEMPORARY CLINICAL STAFF IN THE NHS: AN HSJ INVESTIGATION. PMID- 26882780 TI - ON THE SPENDING REVIEW: Osborne's 'magic sofa' might bring discomfort. PMID- 26882782 TI - THE STATUS QUO IS NOT AN OPTION FOR CCGs. PMID- 26882781 TI - STOP VICTIMISING BEREAVED FAMILIES. PMID- 26882783 TI - TIME TO HAND OVER POWER. PMID- 26882784 TI - Effectiveness and Safety of a Clinical Decision Rule to Reduce Repeat Ionized Calcium Testing: A Pre/Post Test Intervention. AB - The American Recovery and Reinvestment Act authorizes the Centers for Medicare and Medicaid Services to reimburse hospitals that demonstrate meaningful use of certified electronic health record technology. We sought to demonstrate meaningful use by developing and implementing one clinical decision support rule in the computerized physician order entry system that targets clinician-ordered repeat ionized calcium measurement at the University of Connecticut Health Center. The rule consists of a pop-up computer reminder that is triggered by ordering a second ionized calcium test within 72 hours after an initial normal test, with no clear indication for repeat testing. We implemented the rule on December 14, 2010, and have reviewed all data collected through December 2014. We found that the number of repeat tests decreased from 46% to 14% with no significant increase in the number of serious adverse events. We conclude that computerized reminders can decrease unnecessary repeat testing in the inpatient setting. PMID- 26882785 TI - Retinal Detachment and Symptomatic Hypercalcemia in a Patient with Sarcoidosis: Unusual Presentation of a Granulomatous Disease. AB - Sarcoidosisis amultisystemic granulomatous disease, potentially affecting any organ system of the body. Calcium metabolism disturbances occur in up to 20% of patients, of which hypercalciuria and asymptomatic hypercalcemia are most common. Ocular sarcoid typically presents with anterior chamber manifestations such as uveitis, iritis, and iridocyclitis, but can involve posterior chamber as well. We describe herein a unique presentation of sarcoidosis with retinal detachment and symptomatic hypercalcemia as its first manifestation. Prompt therapy with steroids is indicated in these cases, and an immediate ophthalmology referral cannot be overemphasized. PMID- 26882786 TI - Singing the "Minocycline Blues". AB - A variety of medical conditions and medications can lead to cutaneous dyschromia. We report a case of minocycline dyschromia that had been mistakenly attributed to chronic actinic purpura. PMID- 26882787 TI - Primary Hepatic Neuroendocrine Carcinoma: Case Reports and Review of the Literature. AB - Primary neuroendocrine tumors of the liver are exceedingly rare, and unlike metastatic neuroendocrine tumors, rarely cause carcinoid syndrome. There are fewer than 150 cases reported in the current literature. We report two cases of primary hepatic neuroendocrine carcinomas of the liver. Both patients remain healthy without any recurrence to date. A review of the current literature regarding diagnosis, pathology, and management of this disease is included. PMID- 26882788 TI - An Unusual Cause of a Solitary Lung Cavity. AB - Sarcoidosis is a systemic granulomatous disease of unknown etiology. Pulmonary involvement is common, but lung nodules in sarcoidosis are uncommon, and solitary nodules that cavitate are extremely rare. Nodular sarcoidosis is usually found in young, healthy, predominantly female individuals. These lesions need to be differentiated from multiple other conditions, including neoplasms and granulomatous infections. A thorough workup for other etiologies of cavitary lung lesions is required for diagnosis. Despite an ominous presentation, nodular cavitary sarcoidosis portends a favorable outcome. We report a patient who presented with a solitary cavitary nodular lung lesion that was diagnosed as sarcoidosis after extensive workup. PMID- 26882789 TI - The Rise and Fall of Accelerated Partial Breast Irradiation via Brachytherapy in a Single Institution. AB - Accelerated partial breast irradiation via brachytherapy (APBI-b) is offered as an alternative to whole breast irradiation (WBI) for selected patients with breast cancer. This study evaluates our clinical experience with APBI-b to identify the reasons for decreased clinical utilization in recent years. We performed an analysis of the prospective database of breast cancer patients treated with APBI-b between 2004 and 2013. During that time, 245 patients received APBI-b, most having stage I (77%) or stage 0 (20%) breast cancer. Since 2004, the number of APBI-b cases per year rose to 49 in 2009, declining thereafter to 14 in 2013 (P < 0.001). The APBI-b case volume dropped in 2010 following the publication of the American Society of Radiation Oncology (ASTRO) consensus guidelines in 2009. After 2009 fewer unsuitable cases received APBI-b (11% vs. 4%,P = 0.1). CONCLUSION: The clinical utilization of APBI-b has decreased after the publication of consensus guidelines. A reduction in unsuitable cases treated after 2009 does not explain the global loss of referrals. PMID- 26882790 TI - Autosplenectomy Causing Catastrophic Pneumococcal Meningitis in a Patient with Lupus/Antiphospholipid Antibody Syndrome. AB - We present the case ofa26-year-old female who presented to the hospital with pneumococcal meningitis. A review of her records showed atrophic spleen, and a hypercoagulable workup was positive for Systemic Lupus Erythematous (SLE)/Antiphospholipid Antibody Syndrome (APS). An autosplenectomy from thrombotic occlusion of the splenic artery made her susceptible to pneumococcal meningitis. Autoimmune conditions, particularly SLE and APS, are important causes of hypercoagulable states in a young population, and earlier detection of these conditions and appropriate treatment helps to decrease morbidity and mortality among these patients. PMID- 26882791 TI - Transdermal Patches: Considerations in Special Populations. PMID- 26882792 TI - Where Light Shines Through. PMID- 26882793 TI - LETTERS TO THE EDITOR. PMID- 26882794 TI - Physician Burnout: Emotional Exhaustion. PMID- 26882796 TI - Health Insurance Literacy--It's About Transparency. PMID- 26882795 TI - The Present and Future Face of Medicine. PMID- 26882797 TI - [VASCULITIDES IN CHILDHOOD: A RETROSPECTIVE STUDY IN A PERIOD FROM 2002 TO 2012 AT THE DEPARTMENT OF PAEDIATRICS, UNIVERSITY HOSPITAL CENTRE ZAGREB]. AB - The aim of our study was to analyze clinical features, laboratory findings, treatment, course and outcome of different types of vasculitis in children. All children aged up to 18 years that have been diagnosed with a vasculitis disorder from 2002. to 2012. at the Department of Paediatric, University Hospital Centre Zagreb according to EULAR/PRES/PRINTO criteria were included in the study. Vasculitis was diagnosed in 180 children, 101 girls and 79 boys, mean age 7.19 +/ 3.7 years, with an average follow-up of 5.58 +/- 3.28 years. Most of the children (155 or 86%) were diagnosed with Henoch-Shonlein purpura (HSP), polyarteritis nodosa (PAN) was diagnosed in 6 children (3.3%), isolated cutaneous leukocytoclastic vasculitis in 5 (2.8%), Takayasu arteritis (TA) and Kawasaki disease in 2 (1.1%) respectively, hypocomplementemic urticarial vasculitis in one patient (0.5%) and other types of vasculitis in 10 (5.5%) patients (vasculitides in systemic connective tissue disorders in 7 and unclassified vasculitides in 3 patients). All patients had elevated inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Anti-neutrophil cytoplasmatic antibodies (ANCA) were positive only in one patient, suffering from microscopic polyangiitis. Treatment modality in most patients were NSAIDs, while children with kidney or gastrointestinal system affection were treated with glucocorticoids and/or immunosuppresive drugs. Biological therapy (anti-CD20, rituximab) was used in patients with most severe symptoms. One child (0.56%), suffering from microscopic polyangiitis, died due to kidney failure during the follow-up. Forty patients (22.6%) had one disease relapse, while 6 (3.4%) had two relapses. In conclusion, we found some differences in laboratory parameters (e.g. lower incidence of elevated antistreptolysin O titer in HSP) and epidemiological data (e.g. higher prevalence of PAN in female children) in comparison to data from available studies, while other clinical features, laboratory findings, disease outcome and treatment were similar. PMID- 26882798 TI - [RHEUMATOLOGY IN EUROPE IN 2015]. AB - One of the main concerns of people with chronic conditions, particularly rheumatic and musculoskeletal diseases, is the availability of quality health care, which is being analyzed. There are differences between European countries regarding the access to health care. The pressure of the financial crisis has been recognized in making barriers more evident. Representatives of the European Parliament together with stakeholder organizations create policy documents for optimizing access to health care at both the EU and national levels. Great care is taken with the education of medical doctors and other professionals in rheumatology on all educational levels. Based on a recent study, there are similarities and discrepancies in the implementation of the specialty training programs (Chapter 6 of the UEMS Charter of Specialty Training Programmes) across Europe. In the meantime, the UEMS Council has endorsed the new Training Requirements for the Specialty of Rheumatology--European Standards for Postgraduate Medical Specialist Training. The training program is competency based, stressing the important role of professional behaviour. The document is being forwarded to the national societies in order to be implemented in the European countries. A strategy of assessment methods in the specialty training program is being developed. Work on the e-portfolio for European trainees as well as the European Specialty Board Examination is in progress. PMID- 26882799 TI - [BONE MINERAL DENSITY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS--OUR RESULTS]. AB - INTRODUCTION: Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing low bone mass (LBM) or osteoporosis, either because of the disease itself or due to its treatment. Osteoporosis and osteoporotic fractures significantly contribute to morbidity and mortality. We aimed to determine the associations of bone mineral density (BMD) changes with the duration of SLE, age, gender, and glucocorticoid treatment in SLE patients treated at our Department. PATIENTS AND METHODS: BMD measurements of the lumbar spine and total hip were performed by dual-energy X-ray absorptiometry (DXA). Osteoporosis and LBM were determined according to the 1994 World Health Organization definition. In the statistical analysis, the independent Mann Whitney U test and Tukey post-hoc testing were used. RESULTS: The study included 48 SLE patients (44 female and 4 male), with a mean age of 45.8 years and an average SLE duration of 9.8 years. Osteoporosis was diagnosed in 21%, and LBM in 15% of the patients. The mean ages of the subgroups with normal BMD, LBM, and osteoporosis were 41.1, 47.6, and 59.0 years, respectively. Variant analysis showed a statistically significant correlation between age and BMD (p < 0.05). The duration of SLE was significantly shorter in patients with normal BMD (7.3 years), compared to patients with LBM (16.1 years) and osteoporosis (12.9 years) (p < 0.05). Nearly all patients (47 of 48) were on long-term treatment with glucocorticoids. One third (33.3 %) of patients did not take vitamin D3, and 56.3 % did not take calcium supplements. CONCLUSION: The etiopathogenesis of decreased BMD in SLE patients is multifactorial and includes both traditional and SLE related risk factors. In our group of SLE patients age and glucocorticoid treatment were the major risk factors for LBM. Timely prevention and treatment of LBM and osteoporosis in SLE patients, according to current knowledge, are essential for reducing morbidity and mortality. PMID- 26882800 TI - [TAKAYASU ARTERITIS AND POSSIBLE CARDIOLOGY REPERCUSSIONS IN THE CHILDHOOD]. AB - Vasculitides are rare rheumatic diseases of unknown etiology whose main characteristic is a necrotizing inflammation of blood vessels. We are presenting two patients with Takayasu arteritis (TA) as entity forms of rare rheumatic diseases. One patient had TA type IIa and the other type IV. In the first patient we found severe symptoms of obstructive lesions of aortic branches, particularly severe coronary artery stenosis and complete occlusion of the left subclavian artery, and thoracic artery stenosis below the isthmus. The disease was diagnosed in the acute phase, treated extensively with medicaments (glucocorticoids, cytostatics, methotrexate) and a complex cardiac surgical procedure, and due to relapse the biological (Rituximab) therapy was used. The second patient was detected following symptomatic arterial hypertension, with absent pulses of lower limbs, whose cause was found in severe narrowing of the aorta from diaphragm to femoral arteries bifurcation (mid-aortic syndrome). The disease was not active when diagnosis was made. The patient was treated with a particular cardiac surgical procedure and with multiple medicaments due to a relapse. Both patients have reached adolescent age and are successfully treated with a satisfying quality of life. Type IIa with an additional occlusion of coronary arteries is not described in the available literature. Forementioned vasculitides emphasize the importance of pediatric cardiologists and rheumatologists teamwork. PMID- 26882801 TI - [PROF. DR. HANS GEORG FASSBENDER (1920-2015)]. PMID- 26882802 TI - Could Blood Neutrophil Gelatinase-Associated Lipocalin (NGAL) be a Diagnostic Marker for Acute Kidney Injury in Neonates? A Systemic Review and Meta-Analysis. AB - BACKGROUND: Blood neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be helpful for acute kidney injury (AKI) in pediatric patients and adults. Whether this is true in neonates remains unclear. METHODS: A systemic review and diagnostic meta-analysis was performed. Keywords included blood NGAL/serum NGAL, neonate/newborn, and AKI/acute kidney failure. Eligible studies measured blood or serum NGAL levels in neonates with AKI (first 30 days of life). Studies were excluded if they did not present sufficient data to extract or calculate true positives, false positives, false negatives, and true negatives, or were not available in English. RESULTS: Five of 50 studies were included with 159 critically ill neonates and 251 measurements of blood NGAL concentrations. The overall pooled positive and negative likelihood ratios were 5.84 (95% CI 2.68 - 12.75) and 0.23 (95% CI 0.14 - 0.38). The area under the receiver operating characteristic curve was 0.87 and the Q value was 0.823. The overall pooled sensitivity and specificity of all studies were 0.813 (95% CI: 0.697 - 0.891) and 0.859 (95% CI: 0.730 - 0.932). The pooled diagnostic odds ratio was 27.20 (95% CI 8.84 - 83.74), with Cochran's Q = 4.07 (p = 0.397). No publication bias was found. CONCLUSIONS: Blood NGAL could be used as diagnostic marker for AKI in neonates. PMID- 26882803 TI - 5-Aza-2'-Deoxycytidine and CDDP Synergistically Induce Apoptosis in Renal Carcinoma Cells via Enhancing the APAF-1 Activity. AB - BACKGROUND: It has been reported that the hypermethylation of APAF-1, DAPK-1 and other tumor suppressive genes (TSGs) correlates with progression of renal cell carcinoma and exerts prognostic and diagnostic relevance in renal cell carcinoma. A recent study has confirmed that demethylation regulates the TSGs expression and proliferation of various types of cancer cells. The present study was to recognize a potential anti-tumor effect of 5-aza-2'-deoxycytidine (DAC), a demethylation agent. METHODS: We evaluated the DNA demethylation by DAC in human renal carcinoma cells and determined the synergism of the demethylation with the toxicity of Cisplatin (CDDP), which is a commonly utilized anti-tumor agent for renal carcinoma. RESULTS: It was demonstrated that DAC promoted a significant global genomic demethylation and improved APAF-1 expression at both mRNA and protein levels. The DAC treatment deteriorated the CDDP-induced viability decreasing Caki or ACHN cells and synergized the apoptosis induction of CDDP in ACHN cells. The treatment with both DAC and CDDP promoted a significantly higher level of renal carcinoma cell apoptosis than singular DAC or CDDP treatment. The APAF-1 knockdown significantly inhibited the synergism of DAC with the CDDP induced apoptosis in ACHN cells. CONCLUSIONS: The present study confirmed that DAC demethylated the CpGs, particularly APAF-1 in renal carcinoma cells, and that the demethylation synergized the cytotoxity of CDDP in renal carcinoma cells via enhancing the CDDP-induced apoptosis. PMID- 26882804 TI - Reference Intervals for Hemoglobin and Age- and Gender-Related Trends in the Population of Southwest China. AB - BACKGROUND: The establishment of a proper reference range is necessary for both the prognosis and diagnosis of clinical disease. Our study aimed to establish the hemoglobin reference interval for the population of Southwest of China and to compare this with published data for other races. METHODS: A total of 21085 healthy individuals (11561 men and 9524 women, age range 18 - 100 years) living in Southwest China were selected. CBC was performed on an XE-2100 hematology analyzer. The medians were calculated and reference values were determined at the 2.5th and 95th percentiles. RESULTS: There was a statistically significant gender difference for RBC count, Hb, and MCV (p = 0.000). The comparison of Hb by gender showed higher values among males, with lower values in females and this difference was similar to the values for RBC count and MCV. For males, mean values for Hb and RBC decreased with age. However, mean values for Hb in females increased after middle age. CONCLUSIONS: Reference intervals for major red blood cell parameters established in this study showed significant gender differences. For males, mean values for Hb and RBC decreased with age. This is the first region-wide population study on hematologic reference values among people in Southwest China. PMID- 26882805 TI - Application of a Quality Control Algorithm Independent of Control Materials in Molecular Testing for Personalized Medicine. AB - BACKGROUND: The application of traditional internal quality control processes in molecular testing for personalized medicine often proves difficult due to limited control materials. We established a quality control algorithm independent of control materials to monitor routine clinical test results. METHODS: A quality control algorithm was constructed based on the parameters p, P(pos), P(neg), and P(con) calculated by an elementary probability theory. This quality control algorithm was applied in CYP2C19 genotyping and EGFR mutation testing in two molecular diagnostics laboratories in order to illustrate how probabilities are calculated and test results are analyzed. RESULTS: For CYP2C19 genotyping, when the p-values based on 151 specimens from 20 runs were used, three runs were out of control within 20 runs, while two of the three runs became acceptable with p values calculated with 362 samples in 40 runs. For EGFR mutation testing, one run was rejected because of the low P(pos)-values of deletion in exon 19 with the p value based on 421 specimens from 40 runs. CONCLUSIONS: The quality control algorithm can be employed to monitor possible false-positives and false-negatives according to the number and distribution of positive results. Noticeably, the evaluation and interpretation of the control results is essential for the decision by a test laboratory to reject a run. PMID- 26882806 TI - Diagnostic Value of Fecal MicroRNAs for Colorectal Cancer: a Meta-Analysis. AB - BACKGROUND: Though the fecal occult blood test is used for colorectal cancer (CRC) screening worldwide, it lacks sensitivity and specificity for screening an average-risk population. Many studies have suggested that fecal microRNAs (miRNAs) might serve as novel diagnostic indicators of colorectal cancer. However, inconsistent results have also been reported. This meta-analysis aimed to evaluate the feasibility of fecal miRNAs as biomarkers for colorectal neoplasia screening. METHODS: We systematically searched PubMed, Embase, and Google Scholar for publications concerning the diagnostic value of miRNAs isolated from stool for CRC screening. The quality of each study was scored using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Data from different studies were pooled to estimate the summary sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) using a bivariate model. Summary receiver operator characteristic curves (SROCs) were plotted, and areas under the SROC curve (AUC) were calculated to evaluate the overall test performance. Heterogeneity was tested with the I2 test, and publication bias was tested with Deeks' funnel plot asymmetry test. Potential sources of heterogeneity were analyzed through subgroup analyses and meta-regression. RESULTS: Eighteen studies from 9 articles, including 853 patients and 819 controls, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, DLR, and DOR were 0.63 (95% confidence interval [CI]: 0.56 - 0.70), 0.86 (95% CI: 0.77 - 0.92), 4.47 (95% CI: 2.85 - 7.01), 0.43 (95% CI: 0.38 - 0.49), and 10.38 (95% CI: 6.85 - 15.73), respectively. The area under the SROC was 0.77. Meta-regression suggested that different countries (or regions) and sample sizes may be potential sources of heterogeneity. CONCLUSIONS: Fecal miRNAs are potentially useful noninvasive biomarkers for the diagnosis of CRC, and combining methylated gene markers or FOBT with miRNA markers may be an alternative approach. PMID- 26882807 TI - Novel Molecular Regulators of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis in NSCLC Cells. AB - BACKGROUND: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in some non-small cell lung cancer (NSCLC) cells, some NSCLC cells exhibit TRAIL-resistance. The underlying mechanisms that regulate TRAIL sensitivity in NSCLC cells are not well understood. The objective of this study was to investigate molecular regulators of the TRAIL pathway in NSCLC cells. METHODS: The TRAIL-sensitive NSCLC cell line NCI-H358 and a TRAIL-resistant cell line A549 were treated with rmhTRAIL for 24 hours. Then cell viability were measured by MTT assay, meanwhile cell cycle and apoptosis were measured by flow cytometry. Furthermore, mass spectrometry (LC MS/MS) was used to identify the difference in the protein expression profiles. Finally, real-time PCR was performed to detect the mRNA expression of TRAIL receptors and apoptotic related proteins. RESULTS: These results confirmed that NCI-H358 cells were sensitive to TRAIL, whereas A549 cells were resistant. Both mRNA and protein levels of voltage-dependent anion-selective channel proteinl (VDAC1), caspase9 (CASP9), and cytochrome c1 (CYC1) were upregulated in H358 cells but downregulated in A549 cells, whereas antiapoptotic protein BAG-2 was downregulated. In addition, TRAIL also causes DR5 low expression in A549 cells. CONCLUSIONS: These results indicate that rmhTRAIL had different anti-tumor activity in different NSCLC cell lines. Downregulation of VDAC1, CYC1, CASP9, and upregulation of BAG-2 might be associated with underlying TRAIL-resistance mechanisms. These findings motivated further studies to explore new therapeutic strategy overcoming TRAIL-resistance of NSCLC cells through modulating dysregulation of the proteins above. PMID- 26882808 TI - Carotid Artery Intima-Media Thickness and Influencing Factors in Hemodialysis Patients. AB - BACKGROUND: To investigate the increase in carotid artery intima-media thickness (IMT) and influencing factors in hemodialysis patients. METHODS: 90 hemodialysis patients were divided into groups according to their dialysis duration; 30 healthy subjects were included as controls. High-frequency Doppler ultrasound was used to calculate the carotid artery IMT in, 12-, 36-, and 60-month groups; biochemical parameters were also measured. Data from different groups were compared and the associations between the risk factors and IMT were investigated. RESULTS: Increased IMT was found in the patients in all groups compared with controls (p < 0.05). IMT was also significantly higher in the 36-month group than in the 12-month group (p < 0.01), while no significant difference in the IMT was found between the 60-month group and the 36-month group. A positive association was found between the carotid artery IMT and systolic pressure (SBP, r = 0.39, p < 0.01), mean arterial pressure (r = 0.291, p < 0.01), C-reactive protein (CRP, r = 0.511, p < 0.01), serum phosphate (r = 0.518, p < 0.01), and calcium-phosphorus product (r = 0.170, p < 0.01); a negative association was found between carotid artery IMT and plasma albumin (r = -0.095, p < 0.01) and prealbumin (r = -0.65, p < 0.01). Multivariate linear regression showed that high SBP (t = 2.004, p < 0.01), high serum phosphate (t = 2.531, p < 0.01), and increased CRP (t = 4.737, p < 0.01) were independent risk factors for IMT increase. CONCLUSIONS: Hemodialysis increased carotid artery IMT associated with dialysis duration; high SBP, high serum phosphate, and increased CRP are independent risk factors for IMT increase, and IMT was also associated with the development of atherosclerosis. PMID- 26882809 TI - The Diagnostic Role of Vitamin D and Cathelicidin Levels in Pelvic Inflammatory Disease. AB - BACKGROUND: The aim of this study was to evaluate the effect of 25-hydroxyvitamin D [25(OH)D] and cathelicidin levels on pelvic inflammatory disease [PID] in reproductive aged women. METHODS: A total of 81 reproductive aged women, 43 with PID and 38 without PID, were included in the study. Five millilitres of venous blood were collected from subjects and controls for complete hemogram and serum for CRP, IL-6, 25(OH)D and cathelicidin. RESULTS: There were significant differences between the study group and the control group for 25(OH)D (study group, 47.3 +/- 2.01 ng/mL, control group, 28.38 +/- 1.35 ng/mL, p = 0.001), for cathelicidin (study group, 165.56 +/- 65.92 ng/mL, control group, 10.34 +/- 6.48 ng/mL, p = 0.001). There was a positive correlation between 25(OH)D, cathelicidin, and other markers (WBC, CRP, and IL-6). Receiver operator curve analysis showed that the best cutoff value for 25(OH)D was 34.25 ng/mL, sensitivity 88%, and specificity 89%, and for cathelicidin 15 ng/mL, sensitivity 91%, specificity 90%. CONCLUSIONS: 25(OH)D and cathelicidin can be used as acute phase reactants like conventional markers in PID. Future studies are needed to understand the roles of these molecules in both diagnosis and follow-up of infectious situations. PMID- 26882810 TI - Autologous Peripheral Blood Stem Cell Transplantation Improves Neural Electrophysiological Function in Patients with ALS. AB - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. In recent years, numerous experimental and clinical studies have demonstrated the efficacy of autologous stem cell transplantation. Electrophysiological measurements are critical to assess the progress and evaluate the prognosis of ALS. The electrophysiological measurements include nerve conduction velocity (NCV), motor nerve conduction velocity (MCV), F-wave, and electromyography (EMG) of motor neurons. The present research examined whether autologous peripheral blood stem cell transplantation (APBSCT) could improve neural electrophysiological function in 21 patients with ALS. METHODS: 21 patients with ALS were injected with autologous peripheral blood stem cells, and the measurements were assessed prior to APBSCT at 1, 3, and 6 months after transplantation. The analyses were performed using SPSS for Windows 17.0. RESULTS: APBSCT increased the amplitude of the compound muscle action potential (CMAP) and the frequency of the F-wave. This increase was significant at the 6 month follow-up. We failed to detect improvement in the MCV or the distal motor latency (DML). CONCLUSIONS: These preliminary observations suggest that APBSCT improved the electrophysiological function of motor neurons in ALS patients and therefore slowed the progression of the disease. PMID- 26882811 TI - Evaluation of Aging and Health Status in Real Time Based on Routine Urinalysis Using an Automated Urine Analyzer. AB - BACKGROUND: To develop a quantitative system to enable straightforward objective assessment of health status in real time. METHODS: On the basis of routine urinalysis with an automated urine analyzer, we obtained the urinalysis ill health index (UIHI), which was the sum of urinary protein, pH, specific gravity, and color. Clinical laboratory parameters including stress indicators (neutrophilic leukocytes and glucose) and over-nutrition indicators (triglycerides, cholesterol, and uric acid) were monitored. The electrocardiography and blood pressure were also examined. A total of 1128 subjects were selected randomly from those who underwent physical examination to verify the UIHI. RESULTS: The range of the UIHI score was 0 to 5. The cutoff value was 2.75. There were correlations of UIHI score with laboratory parameters and abnormal rates of BP and ECG. A greater UIHI score reflected worse health status (p < 0.05). CONCLUSIONS: These data suggest that the UIHI can reflect the health status of an individual. It can be derived easily from routine urinalysis in a clinical laboratory and may be a useful tool for the quantitative differentiation of health status in real time. PMID- 26882812 TI - The Effects of Valsartan and Amlodipine on the Levels of Irisin, Adropin, and Perilipin. AB - BACKGROUND: Hypertension and obesity are two major threats for public health. Up to the present, antihypertensive medications have been used to lower blood pressure, which seem to provide a better life with lower morbidity and mortality rates. Their effect on etiopathogenesis of hypertension is now an area of developing research. The association between hypertension and obesity also suggests the link between antihypertensive agents and energy hemostasis. We aimed to investigate the effects of antihypertensive treatment on the irisin, adropin, and perilipin levels in patients with essential hypertension and to compare them with healthy volunteers in terms of their effect on energy hemostasis. METHODS: In total, 85 newly diagnosed patients with untreated essential hypertension were admitted to the outpatient clinic. Patients were randomized to one of the following treatment protocols: amlodipine or valsartan for a 12 week period. 42 patients were randomized into the valsartan group and 43 patients into the amlodipine group. Serum perilipin, irisin, and adropin levels were measured before and after drug treatment by ELISA kits. RESULTS: We discovered that the hypertensive patients have lower levels of perilipin and higher levels of adropin compared with the control group. Both amlodipine and valsartan increased the levels of perilipin, irisin, and adropin after 12 weeks of treatment. CONCLUSIONS: In conclusion, in regulating energy balance, perilipin, irisin, and adropin, could be of pathogenic importance in obesity-induced hypertension. Hence, ongoing trials need to elucidate this mechanism. PMID- 26882813 TI - A Single Nucleotide Polymorphism in the FOXP3 Gene Associated with Behcet's Disease in an Iranian Population. AB - Background: Behcet's Disease (BD) is a rare autoimmune disease that involves the dysfunction of regulatory T cells. FOXP3 is a key transcription factor in the development and function of T(reg) cells. Recent studies have shown SNPs in the FOXP3 contribute to the susceptibility to some autoimmune disorders. METHODS: To clarify the association between the FOXP3 gene and the risk of BD, 50 patients diagnosed with BD and 50 healthy controls from north-western Iran were genotyped by PCR-RFLP (Mun I and Pst I) for two SNPs including rs3761547 (-3499T/C) and rs3761548 (-3279 C/A) in the promoter region of the FOXP3 gene. In addition, a 506 bp nucleotide sequence of FOXP3 promoter was analyzed. RESULTS: The allele 3279 C/A was significantly associated with BD [p = 0.002; odds ratio (OR) = 3.841; 95% confidence interval (CI) 1.610 - 9.161]; whereas, there was no contribution of the FOXP3 polymorphism -3499T/C to BD [(p = 0.084); (OR = 0.348, 95% CI = 0.101 - 1.195)]. Meanwhile, sequence analysis showed 100% similarity in both controls and BD patient groups. CONCLUSIONS: Therefore, the SNP rs3761548 in the FOXP3 gene appears to contribute to the risk of Behcet's disease among the north-western Iranian population. PMID- 26882814 TI - Association of Genetic Polymorphisms in UDP-Glucuronosyltransferases 2B17 with the Risk of Pancreatic Cancer in Chinese Han Population. AB - BACKGROUND: This study is aimed to investigate the association between polymorphisms in UGT2B17 and the risk of developing pancreatic cancer in Chinese Han population. METHODS: A hospital-based case-control study was conducted, and 1579 healthy controls and 406 pancreatic cancer patients were enrolled. Real-time PCR was applied to identify the genetic polymorphisms in the subjects, and multivariable logistic regression analysis was performed to investigate the association between UGT2B17 polymorphisms and susceptibility to pancreatic cancer. RESULTS: The prevalence of the UGT2B17 del/del, del/ins, and ins/ins in cases were 72.9%, 24.0%, and 3.1%, respectively, and in controls 66.6%, 30.7%, and 2.7%, respectively. Multivariable logistic regression revealed that, compared with the del/del genotype, the del/ins genotype in UGT2B17 is related to a significant reduction in pancreatic cancer risk (OR = 0.77, 95% CI = 0.60 - 0.99; P = 0.04). In the female subjects, compared with the del/del genotype, the del/ins genotype was related to a substantial reduction in pancreatic cancer risk (OR = 0.59, 95% CI = 0.39 - 0.90, P = 0.01). CONCLUSIONS: All these results indicate a higher ratio of UGT2B17 deletion polymorphisms in Asians. UGT2B17 deletion polymorphisms are associated with the risk of developing pancreatic cancer in Chinese Han population, especially in the female population. PMID- 26882815 TI - The Evaluation of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein Levels in Patients with Acute Attack of COPD. AB - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD) are characterized by the release of inflammatory mediators. The aim of this study was to compare serum levels of pentraxin 3 (PTX3) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute exacerbations of COPD with those of a healthy control group. METHODS: The study included 107 men and 19 women, with mean age of 66.5 (32 - 87) years who were diagnosed with acute COPD exacerbations and 48 healthy individuals as a control group. The serum PTX3 and hs-CRP levels were measured and pulmonary function tests were performed. RESULTS: The mean serum level of the hs-CRP was 39.56 mg/L (10.10 - 262), and it was higher in the COPD group than in the control group (p < 0.0001). The hs-CRP levels increased in accordance with the severity of the COPD (p < 0.0001). The serum PTX3 level was 0.52 pcg/dL (0.42 - 0.56) in acute exacerbations. There was a correlation between the PTX3 levels and the pulmonary function tests, including FEV1, FVC, and FEV1/FVC (r = 0.317, p < 0.001; r = 0.385, p < 0.0001, and r = 0.248, p = 0.001, respectively). CONCLUSIONS: The short pentraxin hs-CRP is elevated in COPD patients with acute exacerbations and correlates with the severity of the disease compared with the long pentraxin PTX3. These results support the idea that hs-CRP can be used as an earlier determinant of inflammation in COPD acute exacerbations and that PTX3 cannot be used as a marker of acute exacerbation and disease severity. PMID- 26882816 TI - Decreased Serum miR-503 Level in Children with Nephrotic Syndrome. AB - BACKGROUND: Serum microRNAs (miRNA, miR) are suggested to have great potential to serve as biomarkers. In this study, we explored the clinical role of serum miRNAs which may play key roles in childhood nephrotic syndrome (NS). METHODS: Serum samples were obtained from 150 NS children and 109 age/gender-matched healthy controls. The levels of serum miRNAs were analyzed using the TaqMan Low Density Array and then validated with RT-qPCR assay. Pathological changes were examined in NS children with immunohistochemical analysis. The effects of miR-503 on cell proliferation and cell cycle were explored using MTT assay and flow cytometry in rat mesangial cells (RMCs). Western blot analysis was applied to determine the effect of miR-503 on cell cycle-related proteins. RESULTS: The concentration of serum miR-503 was highly decreased in NS children compared with controls (p < 0.0001). In NS children, we found obvious enhancement of cell proliferation marker Ki-67 by immunohisto- chemistry. Moreover miR-503 mimics significantly extended the G0/G1 phase and decreased the G2/M phase in comparison with the negative control group. Overexpression of miR-503 obviously reduced the levels of cyclin E. Luciferase reporter assay revealed that cyclin E was the target of miR 503. CONCLUSIONS: In this study, we determined that serum miR-503 was significantly decreased in NS children. MiR-503 contributes to the aberrant proliferation of RMCs by targeting cyclin E, which may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS. PMID- 26882817 TI - The Assessment of Liver Reserve Function by Spectrophotometry based on Determination of Phenacetin and Paracetamol. AB - BACKGROUND: To establish a technical system for assessing liver reserve function based on spectrophotometry by detection of phenacetin and paracetamol in blood samples. METHODS: Taking detected contents of phenacetin and paracetamol by high performance liquid chromatography (HPLC) as standard, which was proved to be able to detect drug concentrations with high resolution and accuracy, we established a technical system based on the spectrophotometric technique to assay phenacetin and paracetamol, including the color system, the maximum absorption wavelength, the influence factors of color system, and the optimal conditions for hydrolysis. Then we verified our established system compared with that under HPLC by recovery test. RESULTS: This study established a technical system to detect phenacetin and paracetamol in blood samples using spectrophotometry. Mainly, 3 mol/L hydrochloric acid (HCl) was added to samples for hydrolysis for 30 minutes, then, adding 0.02% 1,2-naphthoquinone-4-sulfonate (NQS), 1% cetyltrimethyl ammonium bromide (CTA) and 2% sodium hydroxide (or 3% sodium carbonate) (ratio of 1:6:1:2 or 3), and the absorbance was measured at 500 nm and 570 nm to calculate their concentrations. CONCLUSIONS: Using an established spectrophotometric system to detect phenacetin and paracetamol in blood samples could assess liver reserve function, which was proved comparable with HPLC in resolution and repeatability. PMID- 26882818 TI - Is There a Link Between Changes in Levels of Hepcidin and Stroke? AB - BACKGROUND: Iron is an essential element for the living body. It is well known that iron homeostasis disorders are important in two ways--its deficiency and its overload lead to several pathologies. METHODS: We measured 17 patients with iron deficiency anemia (IDA); 19 with anemia of chronic diseases (ACD); 15 with ischemic stroke (IS). The results were compared to a previously selected control group. For evaluation of iron metabolism status, we measured serum iron levels, ferritin, and soluble transferrin receptors. For inflammation, serum interleukin 6 and hsCRP were measured. Serum hepcidin quantification was performed using a previously validated immunosorbent method. Ferritin was measured by an ECLIA method; serum iron on AAS; hsCRP using a nephelometric analysis. RESULTS: We found statistically significant elevated serum hepcidin levels in patients with ACD and IS compared to the control group (p < 0.001). Patients with IDA had statistically significant lower hepcidin levels compared to the control group (p < 0.001). Serum ferritin levels in the IS group was higher compared to the control and other groups (p < 0.001). The lowest ferritin concentrations were established in the IDA group compared to the control (p < 0.001). We found a strong correlation between serum hepcidin and ferritin levels in the IS group (r = 0.583; p < 0.001). CONCLUSIONS: Quantification of serum hepcidin levels might be used as a link for prediction of acute ischemic stroke and future therapeutic influences. PMID- 26882819 TI - Relationship between Serum Resistin Level of Xinjiang Uygur and Han Subjects with Metabolic Syndrome. AB - BACKGROUND: Xinjiang is a multi-ethnic region of China. Many large population based cross-sectional studies have shown that Uygur, the largest ethnic group in the Xinjiang, had a higher incidence rate of metabolic syndrome (MetS) than other ethnic groups living in Xinjiang region, but the pathological mechanism is not yet clear. Insulin resistance plays a critical role in the pathogenesis of MetS. Resistin is an adipocyte- and monocyte-derived cytokine that represents a link between obesity, insulin resistance, and type 2 diabetes. The aim of this study is to examine the relationship between serum resistin levels and metabolic syndrome parameters in Uygur and Han in Xinjiang. METHODS: Subjects came from a population based cross-sectional study, a total of 465 subjects were selected for the study. Blood resistin, fasting blood sugar (FBS), fasting insulin (FINS), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), waist circumference (WC), body mass index (BMI), systolic blood pressures (SBP), diastolic blood pressures (DBP), and the homeostasis model assessment-estimated insulin resistance (HOMA IR) indices were measured. Dietary intake data were obtained by food frequency questionnaire method. The International Diabetes Federation (IDF) criteria were adopted to define metabolic syndrome. RESULTS: The MetS group has higher metabolic parameters of FPG, TG, TC, DBP, SBP, WC, BMI, LDL-C, and low HDL-C than the non-MetS group, Uygurs have higher FPG and WC than Hans, and Hans have higher TC, TG, and FINS than Uygurs, even after adjusting for age, gender, and BMI, indicating ethnic differences in MetS-related parameters. There was no significant difference in serum resistin levels between the MetS and non-MetS group, as well as between the Uygur and the Han ethnic groups, but a significant positive correlation was found between serum resistin levels with FIN, HOMA, and diet fat. CONCLUSIONS: In our study, we did not observe significant differences in serum resitin levels between the MetS and non-MetS group, regardless of ethnicity. However, serum resistin was positively associated with insulin resistance markers, suggesting that resistin may be an independent determinant for insulin resistance, or indirectly contribute to the development of MetS. Therefore the role of resistin in MetS warrants further investigation. PMID- 26882820 TI - A Comparison of Three Widely Used Immunoassay Systems in Cortisol Measurement. AB - BACKGROUND: Interassay variability is one of the challenging issues of routine clinical laboratory practice. Commercial plasma cortisol immunoassays are also subject to this issue. In this study, we intended to evaluate the interchangeability of cortisol results of three widely used immunoassay systems. METHODS: The cortisol values of 150 serum samples measured by three immunoassay systems, Beckman Coulter DXI 800, Roche Modular E170, and Siemens Immulite 2500, were compared. RESULTS: A degree of proportional biases was observed between all three methods; DXI 800 showed the worst biases with the other two systems (slope values 0.67 and 0.77 with E170 and Immulite 2500, respectively). DXI 800 showed poor agreement with other methods (CCC: 0.83 and 0.87, respectively). There was a moderate agreement between E170 and Immulite 2500 (CCC: 0.92). CONCLUSIONS: All three methods showed a degree of variability among themselves. DXI 800 results were not interchangeable with the other two systems. PMID- 26882821 TI - Optimization of the Original TRIzol-Based Technique Improves the Extraction of Circulating MicroRNA from Serum Samples. AB - BACKGROUND: MicroRNAs (miRNAs) are a group of small endogenous, non-coding RNA molecules that have been demonstrated to be essential regulators of many critical biological and pathological processes. Because of their high stability in blood and the strong implication of miRNA expression profiles for human diseases, miRNAs are currently emerging as promising circulating biomarkers for the diagnosis or prognosis of a variety of human diseases. The TRIzol-based technique has been widely used for cell or tissue RNA extraction because of its economy and reliability. However, the original TRIzol-based RNA isolation protocol was not specifically designed for microRNA extraction from serum samples. When it was used to extract serum microRNAs, due to the short sequence and low level of microRNAs, the isolation efficiency in most cases could not meet the requirement. To address this issue, in this study, an improved TRIzol-based protocol was established by modifying the extraction procedure of the original TRIzol-based protocol. The performance of the improved TRIzol-based protocol was evaluated by comparison with other methods. METHODS: Total RNA was isolated by the improved TRIzol-based method, the original method, and two other commonly used methods. RT qPCR and spectrophotometry were used to examine the quality and yield of total RNA. RESULTS: The improved method was more efficient than the original protocol and more suitable for real-time PCR-based profiling experiments. CONCLUSIONS: The optimized TRIzol-based method described in this report is suitable for the extraction of serum microRNAs and useful for the development of microRNAs as diagnostic biomarkers. PMID- 26882822 TI - Sustained Appearance of Urinary Podocytes Suggests Poor Renal Prognosis in Kidney Transplant Patients with Focal Segmental Glomerulosclerosis: Case Reports and Review of Literature. AB - Recent studies have indicated that the detection of urinary podocytes holds major significance for focal segmental glomerulosclerosis (FSGS). We present two cases of FSGS after kidney transplantation, focusing on urinary podocytes. In Case 1, treatment led to incomplete remission with the reduction of urinary podocytes, and his renal function was preserved. Case 2, however, showed continuous increase in proteinuria with loss of renal function despite apheresis. Urinary podocytes remained high throughout. On the basis of this experience, we suggest the significance of the detection of urinary podocytes for determining renal prognosis in FSGS following renal allograft. PMID- 26882823 TI - Molecular Characterization of a Novel Missense Mutation (Asp538Asn) in a Chinese Patient with Factor XII Deficiency. AB - BACKGROUND: Congenital factor XII (FXH) deficiency is an autosomal recessive disorder whose genetic basis has been described in a relatively small number of cases. METHODS: Recently, we studied a Chinese family in which the proband had obviously prolonged activated partial thromboplastin time (APTT) associated with low functional and antigen FXII levels, 5% and 6.8%, respectively. To investigate the molecular defects in this FXII-deficient patient, we performed FXII mutation screening and invitro expression studies. RESULTS: Sequence analysis of the FXII gene revealed a heterozygous G>A transition at nucleotide 8597 in exon 13, causing a novel Asp538Asn mutation in the catalytic domain. CONCLUSIONS: From the results above, we reasoned that this mutation must confer a cross-reacting material (CRM) negative phenotype. Additional expression studies in COS-7 cells showed that the antigen level of mutant FXII (FXII-Asp538Asn) was lower compared to the wild type in culture media, whereas the corresponding level of FXII antigen in cell lysates was equivalent roughly to that of the wild type. These findings indicated that the Asp538Asn mutation results in intracellular degradation of the mutant FXII and causes FXII deficiency. PMID- 26882824 TI - 1471 delTTCT a Common Mutation of Tunisian Patients with Lysinuric Protein Intolerance. AB - BACKGROUND: Lysinuric protein intolerance is an inherited aminoaciduria caused by defective cationic amino acid transport. It is an autosomal recessive disease caused by mutations in the SLC7A 7 gene. The objective of this study was to identify the mutations of Tunisians patients in order to offer the genetic counseling and the prenatal diagnosis to families. METHODS: Five affected Tunisian children (4 girls and 1 boy) belonging to four consanguineous families were considered. The diagnosis was made based on the plasma for amino acids quantification by Ion Exchange chromatography, the DNA for mutational analysis by DHPLC and sequencing, and the amniotic fluid for prenatal diagnosis. RESULTS: For the 5 patients, clinical features were dominated by failure to thrive, bone marrow abnormalities, hepatosplenomegaly, and mental retardation. The diagnosis for all patients was confirmed by biochemical analysis with hyperammonemia, hyperexcretion of urinary dibasic amino acids, and a high amount of orotic acid in the urine. The 1471 delTTCT mutation was identified in exon 9 in the homozygous state for all Tunisian patients. Genetic counseling was performed for three out of four families, four heterozygous and two homozygous healthy siblings were identified. The result of prenatal diagnosis showed the presence of the 1471 de1TTCT mutation in the homozygous state for the third pregnancy and heterozygous state for the fourth. CONCLUSIONS: The 1471 deITTCT mutation seems to be a common mutation of Tunisian population. The identification of this specific mutation provides a tool for confirmatory diagnosis, genetic counseling, and prenatal diagnosis. PMID- 26882825 TI - The use of adaptive statistical iterative reconstruction (ASiR) technique in evaluation of patients with cervical spine trauma: impact on radiation dose reduction and image quality. AB - OBJECTIVE: The aim of this study was to evaluate the impact of adaptive statistical iterative reconstruction (ASiR) technique on the image quality and radiation dose reduction. The comparison was made with the traditional filtered back projection (FBP) technique. METHODS: We retrospectively reviewed 78 patients, who underwent cervical spine CT for blunt cervical trauma between 1 June 2010 and 30 November 2010. 48 patients were imaged using traditional FBP technique and the remaining 30 patients were imaged using the ASiR technique. The patient demographics, radiation dose, objective image signal and noise were recorded; while subjective noise, sharpness, diagnostic acceptability and artefacts were graded by two radiologists blinded to the techniques. RESULTS: We found that the ASiR technique was able to reduce the volume CT dose index, dose length product and effective dose by 36%, 36.5% and 36.5%, respectively, compared with the FBP technique. There was no significant difference in the image noise (p = 0.39), signal (p = 0.82) and signal-to-noise ratio (p = 0.56) between the groups. The subjective image quality was minimally better in the ASiR group but not statistically significant. There was excellent interobserver agreement on the subjective image quality and diagnostic acceptability for both groups. CONCLUSION: The use of ASiR technique allowed approximately 36% radiation dose reduction in the evaluation of cervical spine without degrading the image quality. ADVANCES IN KNOWLEDGE: The present study highlights that the ASiR technique is extremely helpful in reducing the patient radiation exposure while maintaining the image quality. It is highly recommended to utilize this novel technique in CT imaging of different body regions. PMID- 26882826 TI - Light manipulation of nanoparticles in arrays of topological defects. AB - We report a strategy to assemble and manipulate nanoparticles arrays. The approach is based on the use of topological defects, namely disclination lines, created in chiral liquid crystals. The control of nanoparticle-loaded topological defects by low power light is demonstrated. Large-scale rotation, translation and deformation of quantum dots light-emitting chains is achieved by homogeneous LED illumination. Full reconfigurability and time stability make this approach attractive for future developments and applications. PMID- 26882828 TI - [Ophthalmic formulations new goals]. PMID- 26882827 TI - In Situ Characterization of the Local Work Function along Individual Free Standing Nanowire by Electrostatic Deflection. AB - In situ characterization of the work function of quasi one dimensional nanomaterials is essential for exploring their applications. Here we proposed to use the electrostatic deflection induced by work function difference between nanoprobe and nanowire for in situ measuring the local work function along a free standing nanowire. The physical mechanism for the measurement was discussed in details and a parabolic relationship between the deflection and the potential difference was derived. As a demonstration, measurement of the local work functions on the tip and the sidewall of a ZnO nanowire with Au catalyst at its end and a LaB6 nanowire have been achieved with good accuracy. PMID- 26882829 TI - Analysis of the concordance between the estimated values of creatinine clearance using the Cockcroft-Gault equation and the real value determined in patients from the Hospital Clinica Biblica. AB - OBJECTIVE: to analyze the effect of the modifications in the Cockcroft-Gault equation for creatinine clearance rate determination (CrCl) and its concordance with the real value determined from 24-hours urine collection in a sample of Latin American patients hospitalized in San Jose de Costa Rica. METHOD: an observational, retrospective study, with patients submitted to a 24-hour urine collection test, and who met the inclusion criteria. The real and estimated values of creatinine clearance were determined, and their concordance was measured by applying the Intraclass Correlation Coefficient; a descriptive analysis of data was also conducted. RESULTS: there were 507 subjects (61% men); their age was described (ME = 60 years SD = 17 years), as well as their height (ME = 1.66 m SD = 0.09 m), current weight (ME =75 kg SD = 15 kg), body mass index (ME = 27.3 kg/m2 SD = 4.76 kg/m2) and endogenous creatinine clearance rates (ME = 69.72 ml/min SD = 33 ml/min). The best concordance with the equation was obtained with current weight values and serum creatinine without rounding. CONCLUSIONS: the application of the Cockcroft-Gault equation that matches more closely the real value is the one that uses current weight and does not round creatinine values below 1 mg/dL. It is suggested to conduct a prospective analysis, determining other variables that could affect CrCl real measures, and to replicate this methodology in specific populations. *ME: Mean **SD: Standard Deviation. PMID- 26882830 TI - Chemotherapy near the end of life; assessment of the clinical practise in onco hematological in adult patients. AB - OBJECTIVE: ensure a good quality of life in the last phase of onco- hematological patients should be the primary goal, despite this, we have little data at European level and published studies are contradictory. Nevertheless, most of them agree saying that administrating chemotherapy near the end of life impacts negatively in the patients quality of life. The main objective of this study is to analyze the treatment non-aggressiveness parameters in onco-hematological patients. The secondary objective is to do a describing study of the clinical variables of the patients who receive chemotherapy at the end of life and the treatments more used. METHODS: a retrospective observational study was conducted in a tertiary hospital. Both, oncological and hematological patients receiving chemotherapy (oral or intravenous) between January and December 2013 who were receiving chemotherapy in the last 90 days before death, were included. RESULTS: there were 823 patients that were threated between January and December of 2013. Of these 106 (13%) met the inclusion criteria to be analyzed. There were a 14.1% (n = 93) of oncological and a 8.4% (n = 13) of hematologic patients that maintained the antineoplasic treatment during the last three months before death. A 21.7% (n = 23) of the patients received chemotherapy in the last two weeks of life, 41.5% (n = 44) in the last 30 days and 78.3% (n = 83) in the last two months of life. There was a 67.9% (n = 72) of patients that had hospital admissions during their last three months of life, 47,2% (n = 50) during the last month, 33% (n = 35) during the last two weeks and 10,4% (n = 11) during the last three days of life. A 25,5% (n = 27) of patients had more than one hospital admission during their last 90 days. CONCLUSIONS: according to the Earle et al. criteria, our population had been treated aggressively. We need more scientific evidence with consolidate date that allows us to establish a unified criteria for the selection of patients with advanced cancer who may benefit from receiving antineoplasic treatments. PMID- 26882831 TI - Smartphone applications for cancer patients; what we know about them? AB - BACKGROUND AND OBJECTIVE: one of the groups that can benefit most from healthcare applications, are cancer patients. However, not all applications have a sufficient level of evidence. Our objective is to analyze the characteristics of mobile healthcare applications for cancer patients and know the reliability of their information. MATERIAL AND METHODS: a descriptive observational study of mobile apps targeting cancer patients. In November 2014, we searched mobile applications for cancer patients in the App Store (iOS) and Google Play (Android), using the terms "cancer" and "oncology" (English and/or Spanish languages). Applications were downloaded and evaluated. We registered their general characteristics (classification of cancer, last date of actualization, language and others) and their purpose (whether were informative, diagnostic, or preventive purposes) on an Excel(r) chart. The analysis was completed with an internet search to analyze their scientific evidence. RESULTS: one hundred and sixty six applications were downloaded. 23.5% were destined for breast cancer. 52.4% upgraded their software in the last year. 98.2 % were in English. Most of the applications had more than one purpose. The most frequent were informative (39.8%), diagnostic (38.6%) and preventive (28.3%). 50.6% presented sufficient scientific evidence. CONCLUSIONS: there are many benefits that are expected from these applications. However, we detected a lack of validity of the information, as well as lack of update of the data. To prevent these apps from becoming a safety problem rather than a useful tool for patients, regulation should be put in place. PMID- 26882832 TI - [Evaluation of two closed-system drug transfer device in the antineoplastic drug elaboration process]. AB - OBJECTIVE: to assess the impact of two closed-system drug transfer device on the local and environmental contamination and preparation times in the process of preparation of parenteral chemotherapy compared to the standard system. METHOD: prospective observational study. Two different closed- systems providers, Care Fusion(r) and Icu Medical(r), were compared to standard preparation. 15 nurses of Pharmacy Department prepared 5 preparations each one, one with the standard procedure and four using closed-systems. To evaluate the contamination, a fluorescein solution 0.5% was prepared. Two kind of contamination were evaluated, local (three points connection: closed-system connect vial, syringe and final infusion bags) and environmental (gloves and countertop). Percentage of contaminated preparations was obtained in each one. Time taken by each nurse in each preparation was recorded. RESULTS: 75 preparations were prepared. Local contamination was reduced 21% and 75% in closed-system Icu Medical(r) and Care Fusion(r) respectively. Care Fusion(r) closed system, local contamination was significantly lower than the standard system to the vial, syringe and final package, while Icu Medical(r) closed-systems only was significantly lower in the connection to the vial. Time of preparation was increased significantly with the use of closed-system between 23.4 and 30.5 seconds. CONCLUSIONS: both closed systems drug transfer device have shown an improvement in contamination than the use of the standard system. However, preparation time has been significantly increased with the use of both systems. PMID- 26882833 TI - Effect of a single dose of lidocaine and ketamine on intraoperative opioids requirements in patients undergoing elective gynecological laparotomies under general anesthesia. A randomized, placebo controlled pilot study. AB - Background and goal of study: there is evidence that perioperative intravenous ketamine and lidocaine reduce postoperative pain, postoperative opioids consumption, shortens hospital stay and accelerates intestinal function recovery. However, it has not been studied the beneficial effects in the intraoperative period. The aim of this study was to evaluate the effect of a single dose of lidocaine and ketamine on intraoperative opioids requirements in patients undergoing elective gynecological laparotomies under general anesthesia. MATERIALS AND METHODS: we performed a single-centre, prospective, randomized, double-blinded, placebo-controlled study. We included 33 patients (11 in the ketamine group, 11 in the lidocaine group and 11 in the placebo group). Postoperative analgesia was accomplished by patient-controlled morphine. Patients were randomly assigned to receive either a 1.5 mg/kg of 2% lidocaine, 0.5 mg/kg of 5% ketamine or 0.9% saline bolus. The primary outcome was the opioids consumption during surgery. The secondary outcomes included: emergence time, pain scores, opioids consumption within 24 h after surgery and side effects. RESULTS: decreased intraoperative opioids requirements were noted in the experimental groups (ketamine: 402.3 ?} 106.3 and lidocaine: 397.7 ?} 107.5, compared with saline: 561.4 ?} 97.1); p = 0.001. We found a positive correlation between intraoperative opioids consumption and emergence time (r = 0.864, p < 0.001). There was no significant difference between the groups in VAS pain scores at rest within the first 24 postoperative hours. Total morphine consumption within 24 h after surgery did not differ significantly among the groups (placebo: 27.54 ?} 11.75; ketamine: 30.95 ?} 7.88; lidocaine 34.77 ?} 4510.25; p = 0.26). Postoperative nausea and vomiting were more common in placebo group (it was observed in 3 subjects in ketamine group, in 5 subjects in lidocaine group and in 9 subjects in placebo group; p = 0.027). CONCLUSION: our results do not support the use of intraoperative single dose of lidocaine or ketamine to reduce postoperative pain and postoperative opioids consumption after open gynecological surgery. However, they seem to decrease intraoperative opioids requirements and shorten emergence time. Nevertheless, these findings should be validating in further studies with large sample size. PMID- 26882834 TI - [Use of leflunomide in a cytomegalovirus infection resistant: a report of a case]. AB - BACKGROUND AND OBJECTIVE: cytomegalovirus (CMV) infection is one of the most common complications in transplant patients, which can lead to multiple organ failure. The 80-90% of patients are cured with intravenous treatment standard (ganciclovir), or its oral prodrug (valganciclovir). In case there is no answer, we have alternatively another antiviral, foscarnet. A small number of patients do not respond to this, having a bad prognosis. The aim is to describe the case of a double lung transplant for cystic fibrosis, and recurrent CMV infection in which the use of leflunomide gets lower and even reach undetectable viral load. DESCRIPTION OF CASE: woman, 22 year old, double lung transplant for cystic fibrosis in March 2014. The CMV serology performed was positive in the donor and negative in the recipient. Controls viral load during prophylaxis with valganciclovir were negative in the receiver until the 6th month after transplantation, at which viral load was detected in controls (2 090 IU/ml). The patient was admitted to our hospital to receive intravenous treatment with ganciclovir, after one month with intravenous therapy viral load persisted positive (42 400 IU/ml). One study of resistance showed that was resistant to ganciclovir, so began treatment with intravenous foscarnet. This drug achieved negativizar viral load, so the treatment was discontinued, continuing with fortnightly controls viral load. After two months without treatment, viral load increased to 13 665 IU/ml, why was requested to Pharmacy Service the off-label use of leflunomide, with the intention that use oral therapy, instead of intravenous therapy. The patient was treated with valganciclovir until have the authorization of use of leflunomide, although unanswered, since in March 2015, at the start of leflunomide treatment the patient had a viral load of 17 344 IU/ml. The initial regimen was 100 mg of leflunomide daily for the first five days, followed by 20 mg every 12 hours. After fifteen days of treatment viral load had fallen to 531 IU/ml, becoming undetectable in one month. After four months of treatment the patient remains with undetectable viral load without having any adverse effect associated with it. CONCLUSION: our case is an example where the use of leflunomide in CMV infection resistant to other therapies is an effective and convenient alternative for patients because it keeps undetectable viral load with an oral therapy without having to enter the hospital for intravenous treatment. PMID- 26882835 TI - [Mesalazine-induced intersticial pneumonitis in patients with ulcerative colitis]. PMID- 26882836 TI - [Enoxaparin dosage in extreme obesity by monitoring anti-Xa factor]. PMID- 26882839 TI - Plasmonic-enhanced perovskite-graphene hybrid photodetectors. AB - The surface plasmonic effect of metal nanostructures is a promising method to boost the performance of optoelectronic devices such as solar cells and photodetectors. In this report, gold nanoparticles with surface plasmon resonance localized at about 530 nm were synthesized and integrated into graphene/methylammonium lead iodide perovskite (CH3NH3PbI3) hybrid photodetectors. Compared with pristine graphene-CH3NH3PbI3 devices, a device with gold nanoparticles embedded has a doubly higher photo-responsivity as well as a faster photoresponse speed. The present devices adopt a unique configuration with gold nanoparticles physically separated from the light harvesting component, i.e., the perovskite layer by graphene. Advantages are revealed through a series of characterization techniques and analyses. First, thanks to the tiny thickness of graphene, the plasmonic effect of gold nanoparticles can effectively enhance the near-field of perovskite and thus facilitate light-harvesting. Second, the enhanced light-harvesting in perovskite happens very close to this interface where photo-induced carriers have relatively short paths to diffuse toward graphene, favoring a fast photo-response. This work demonstrates a feasible and inspiring strategy to improve the performance of photodetectors through the surface plasmonic effect of metallic nanostructures. PMID- 26882840 TI - Regulators in the DNA damage response. AB - Maintenance of genome integrity is essential for the proper function of all cells and organisms. In response to both endogenous and exogenous DNA damaging agents, mammalian cells have evolved a delicate system to sense DNA damage, stop cell cycle progression, modulate cell metabolism, repair damaged DNA, and induce programmed cell death if the damage is too severe. This coordinated global signaling network, namely the DNA damage response (DDR), ensures the genome stability under DNA damaging stress. A variety of regulators have been shown to modulate the activity and levels of key proteins in the DDR, including kinases, phosphatases, ubiquitin ligases, deubiquitinases, and other protein modifying enzymes. Epigenetic regulators, particularly microRNAs and long noncoding RNAs, have been emerging as an important payer of regulation in addition to canonical DNA damage signaling proteins. In this review, we will discuss the functional interaction between the regulators and their targets in the DDR. PMID- 26882841 TI - Corrigendum: Dual modulation of Ras-Mnk and PI3K-AKT-mTOR pathways: A Novel c FLIP inhibitory mechanism of 3-AWA mediated translational attenuation through dephosphorylation of eIF4E. PMID- 26882842 TI - Divalent Ion Parameterization Strongly Affects Conformation and Interactions of an Anionic Biomimetic Polymer. AB - The description of peptides and the use of molecular dynamics simulations to refine structures and investigate the dynamics on an atomistic scale are well developed. Through a consensus in this community over multiple decades, parameters were developed for molecular interactions that only require the sequence of amino-acids and an initial guess for the three-dimensional structure. The recent discovery of peptoids will require a retooling of the currently available interaction potentials in order to have the same level of confidence in the predicted structures and pathways as there is presently in the peptide counterparts. Here we present modeling of peptoids using a combination of ab initio molecular dynamics (AIMD) and atomistic resolution classical force field (FF) to span the relevant time and length scales. To properly account for the dominant forces that stabilize ordered structures of peptoids, namely steric-, electrostatic, and hydrophobic interactions mediated through side chain-side chain interactions in the FF model, those have to be first mapped out using high fidelity atomistic representations. A key feature here is not only to use gas phase quantum chemistry tools, but also account for solvation effects in the condensed phase through AIMD. One major challenge is to elucidate ion binding to charged or polar regions of the peptoid and its concomitant role in the creation of local order. Here, similar to proteins, a specific ion effect is observed suggesting that both the net charge and the precise chemical nature of the ion will need to be described. PMID- 26882843 TI - Electron tomography characterization of hemoglobin uptake in Plasmodium chabaudi reveals a stage-dependent mechanism for food vacuole morphogenesis. AB - In the course of their intraerythrocytic development, malaria parasites incorporate and degrade massive amounts of the host cell cytoplasm. This mechanism is essential for parasite development and represents a physiological step used as target for many antimalarial drugs; nevertheless, the fine mechanisms underlying these processes in Plasmodium species are still under discussion. Here, we studied the events of hemoglobin uptake and hemozoin nucleation in the different stages of the intraerythrocytic cycle of the murine malaria parasite Plasmodium chabaudi using transmission electron tomography of cryofixed and freeze-substituted cells. The results showed that hemoglobin uptake in P. chabaudi starts at the early ring stage and is present in all developmental stages, including the schizont stage. Hemozoin nucleation occurs near the membrane of small food vacuoles. At the trophozoite stage, food vacuoles are found closely localized to cytostomal tubes and mitochondria, whereas in the schizont stage, we observed a large food vacuole located in the central portion of the parasite. Taken together, these results provide new insights into the mechanisms of hemoglobin uptake and degradation in rodent malaria parasites. PMID- 26882845 TI - The use of MRI deformable image registration for CT-based brachytherapy in locally advanced cervical cancer. AB - PURPOSE: Incorporation of MRI into image-based brachytherapy (IBBT) is limited by logistics, reimbursement, and workflow demands. Our goal is to determine if deformable image registration (DIR) using a preimplantation MRI is feasible to construct a high-risk target volume during IBBT. METHODS AND MATERIALS: From 2010 to 2013, 20 patients were treated with high-dose-rate IBBT for cervical cancer. A preimplantation MRI was fused to the planning CT, and DIR was performed using MIM v6.1. The gross tumor volume (GTV) and high-risk clinical target volume were contoured on the MRI (HR-CTV MRI), and a separate high-risk clinical target volume was made from the deformable image registration of the preimplantation MRI to the planning CT (HR-CTV'). The treated target volume from the planning CT without the DIR or fusion (HR-CTV BT) was compared with the HR-CTV'. The geometric means of the GTV, HR-CTV MRI, HR-CTV', and HR-CTV BT were analyzed. Statistical analysis using Wilcoxon rank and analysis of variance were performed. RESULTS: There was a significant larger difference between the GTV and the HR-CTV MRI, HR-CTV', and HR-CTV BT (p < 0.0001). There was also a significant difference between the HR-CTV MRI vs. the HR-CTV BT (p < 0.040). There was no significant difference between the HR-CTV MRI and HR-CTV'. DIR was advantageous in the setting of residual disease pre-IBBT. CONCLUSIONS: DIR is feasible to define an HR-CTV for MRI-guided, CT IBBT. The HR-CTV MRI predicted a smaller treatment volume in comparison with the HR-CTV BT. DIR is limited by patient anatomy and is most beneficial in patients with gross disease. PMID- 26882844 TI - Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function. AB - Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro pathological role of inefficient DMN suppression in cognitive deficits of first episode schizophrenia. PMID- 26882846 TI - Rasch analysis of the Chedoke-McMaster Attitudes towards Children with Handicaps scale. AB - Aim To assess whether the Chedoke-McMaster Attitudes towards Children with Handicaps (CATCH) 36-item total scale and subscales fit the unidimensional Rasch model. Method The CATCH was administered to 1881 children, aged 7-16 years in a cross-sectional survey. Data were used from a random sample of 416 for the initial Rasch analysis. The analysis was performed on the 36-item scale and then separately for each subscale. The analysis explored fit to the Rasch model in terms of overall scale fit, individual item fit, item response categories, and unidimensionality. Item bias for gender and school level was also assessed. Revised scales were then tested on an independent second random sample of 415 children. Results Analyses indicated that the 36-item overall scale was not unidimensional and did not fit the Rasch model. Two scales of affective attitudes and behavioural intention were retained after four items were removed from each due to misfit to the Rasch model. Additionally, the scaling was improved when the two most negative response categories were aggregated. There was no item bias by gender or school level on the revised scales. Items assessing cognitive attitudes did not fit the Rasch model and had low internal consistency as a scale. Conclusion Affective attitudes and behavioural intention CATCH sub-scales should be treated separately. Caution should be exercised when using the cognitive subscale. Implications for Rehabilitation The 36-item Chedoke-McMaster Attitudes towards Children with Handicaps (CATCH) scale as a whole did not fit the Rasch model; thus indicating a multi-dimensional scale. Researchers should use two revised eight-item subscales of affective attitudes and behavioural intentions when exploring interventions aiming to improve children's attitudes towards disabled people or factors associated with those attitudes. Researchers should use the cognitive subscale with caution, as it did not create a unidimensional and internally consistent scale. Therefore, conclusions drawn from this scale may not accurately reflect children's attitudes. PMID- 26882847 TI - Long noncoding RNA PVT1, a novel promising biomarker to predict lymph node metastasis and prognosis: a meta-analysis. AB - BACKGROUND: Numerous studies have found that the expression levels of long noncoding RNA PVT1 (lncRNA PVT1) were elevated in cancerous tissue, which was significantly higher than those in adjacent noncancerous tissues or corresponding normal tissues. Overexpression of lncRNA PVT1 was correlated with lymph node metastasis and a poor prognosis in various cancers. METHODS: This quantitative meta-analysis collected all relevant articles and explored the association of lncRNA PVT1 expression levels with lymph node metastasis and prognosis. The systematic search was conducted through multiple electronic databases (up to December 1, 2015). The meta-analysis was performed by using RevMan5.3 software and Stata SE12.0. RESULTS: A total of 939 patients with cancer from 10 studies were included. The Meta-analysis results showed that cancer patients with high PVT1 have a strong trend for LNM (OR=2.05, 95%CI:0.97-4.30, P=0.06, random effects model). Moreover, we found that cancer patients with high PVT1 expression had a poorer overall survival (HR=2.07, 95%CI:1.40-2.74, P=0.000, fixed-effects model), a shorter recurrence-free survival (HR=1.70, 95%CI:1.02-2.39, P=0.000, fixed-effects model), and a worse disease-free survival (HR:2.10, 95%CI:0.96 3.23, P=0.000, fixed-effects model). CONCLUSIONS: PVT-1 may serve as a novel molecular marker for lymph node metastasis and prognosis. PMID- 26882848 TI - The Genetic Structure, Virulence, and Fungicide Sensitivity of Fusarium fujikuroi in Taiwan. AB - The rice disease bakanae, caused by Fusarium fujikuroi Nirenberg, has been present in Taiwan for over a century. To better understand the genetic diversity and structure of F. fujikuroi, a set of 16 polymorphic simple sequence repeat (SSR) markers were newly developed and used to analyze 637 F. fujikuroi isolates collected in 14 cities or counties around Taiwan from 1996 to 2013. On the basis of Bayesian clustering, the isolates were classified into four highly differentiated clusters: cluster B likely derived from the more widespread and genetically diversified clusters A or C, and cluster D was restricted to four cities or counties and may have been introduced from unknown sources genetically distinct from clusters A, B, and C. The coexistence of both mating types (MAT1 1:MAT1-2 = 1:1.88) and the highly diversified vegetative compatibility groups (VCG) (16 VCG among the 21 assessed isolates) suggest the likelihood of sexual reproduction in the field. However, the biased mating type ratios and linkage disequilibrium in the population suggest nonrandom mating between individuals. A significant pattern of isolation by distance was also detected, which implies a geographical restricted gene flow and low dissemination ability of F. fujikuroi. Evaluation of 24 representative isolates on eight rice varieties revealed differential levels of virulence, however no clear pattern of specific variety x isolate interaction was observed. Investigations of the differences in virulence and fungicide sensitivity between 8 early isolates (1998 and 2002) and 52 recent isolates (2012) indicate the evolution of increased resistance to the fungicide prochloraz in F. fujikuroi in Taiwan. PMID- 26882849 TI - A Deoxynivalenol-Activated Methionyl-tRNA Synthetase Gene from Wheat Encodes a Nuclear Localized Protein and Protects Plants Against Fusarium Pathogens and Mycotoxins. AB - Fusarium graminearum is the fungal pathogen that causes globally important diseases of cereals and produces mycotoxins such as deoxynivalenol (DON). Owing to the dearth of available sources of resistance to Fusarium pathogens, characterization of novel genes that confer resistance to mycotoxins and mycotoxin-producing fungi is vitally important for breeding resistant crop varieties. In this study, a wheat methionyl-tRNA synthetase (TaMetRS) gene was identified from suspension cell cultures treated with DON. It shares conserved aminoacylation catalytic and tRNA anticodon binding domains with human MetRS and with the only previously characterized plant MetRS, suggesting that it functions in aminoacylation in the cytoplasm. However, the TaMetRS comprises a typical nuclear localization signal and cellular localization studies with a TaMetRS::GFP fusion protein showed that TaMetRS is localized in the nucleus. Expression of TaMetRS was activated by DON treatment and by infection with a DON-producing F. graminearum strain in wheat spikes. No such activation was observed following infection with a non-DON-producing F. graminearum strain. Expression of TaMetRS in Arabidopsis plants conferred significant resistance to DON and F. graminearum. These results indicated that this DON-activated TaMetRS gene may encode a novel type of MetRS in plants that has a role in defense and detoxification. PMID- 26882850 TI - Bismerthiazol Inhibits Xanthomonas citri subsp. citri Growth and Induces Differential Expression of Citrus Defense-Related Genes. AB - Citrus canker, caused by Xanthomonas citri ssp. citri, is a serious disease that causes substantial economic losses to the citrus industry worldwide. The bactericide bismerthiazol has been used to control rice bacterial blight (X. oryzae pv. oryzae). In this paper, we demonstrate that bismerthiazol can effectively control citrus canker by both inhibiting the growth of X. citri ssp. citri and triggering the plant's host defense response through the expression of several pathogenesis-related genes (PR1, PR2, CHI, and RpRd1) and the nonexpresser of PR genes (NPR1, NPR2, and NPR3) in 'Duncan' grapefruit, especially at early treatment times. In addition, we found that bismerthiazol induced the expression of the marker genes CitCHS and CitCHI in the flavonoid pathway and the PAL1 (phenylalanine ammonia lyase 1) gene in the salicylic acid (SA) biosynthesis pathway at different time points. Moreover, bismerthiazol also induced the expression of the priming defense-associated gene AZI1. Taken together, these results indicate that the induction of the defense response in 'Duncan' grapefruit by bismerthiazol may involve the SA signaling pathway and the priming defense and that bismerthiazol may serve as an alternative to copper bactericides for the control of citrus canker. PMID- 26882851 TI - Changes in Plant Metabolism and Accumulation of Fungal Metabolites in Response to Esca Proper and Apoplexy Expression in the Whole Grapevine. AB - Trunk diseases have become among the most important grapevine diseases worldwide. They are caused by fungal pathogens that attack the permanent woody structure of the vines and cause various symptoms in woody and annual organs. This study examined modifications of plant responses in green stem, cordon, and trunk of grapevines expressing Esca proper (E) or apoplexy (A) event, which are the most frequent grapevine trunk disease symptoms observed in Europe. Transcript expression of a set of plant defense- and stress-related genes was monitored by quantitative reverse-transcription polymerase chain reaction while plant phytoalexins and fungal metabolites were quantified by high-performance liquid chromatography-mass spectrometry in order to characterize the interaction between the grapevine and trunk disease agents. Expression of genes encoding enzymes of the phenylpropanoid pathway and trans-resveratrol content were altered in the three organs of diseased plants, especially in the young tissues of A plants. Pathogenesis-related proteins and the antioxidant system were severely modulated in A plants, which indicates a drastic stress effect. In the meantime, fungal polyketides 6-MSA, (R)-mellein, and (3R,4R)-4-hydroxymellein, were accumulated in A plants, which suggests their potential effect on plant metabolism during the appearance of foliar symptoms. PMID- 26882852 TI - Primary Ewing sarcoma of the lumbar spine presenting as cauda equina syndrome in a pediatric patient. PMID- 26882853 TI - A common pathology in an uncommon location: posterior migrated epidural disc herniation. PMID- 26882854 TI - Cervicothoracic intradural arachnoid cyst with scoliosis and brachial plexopathy. PMID- 26882855 TI - Transverse myelitis. PMID- 26882856 TI - Foraminal lumbar root schwannoma. PMID- 26882857 TI - A rare case of cervical myelopathy caused by invaginated laminae of the axis into the spinal canal. PMID- 26882859 TI - Giant retroperitoneal paraspinal liposarcoma causing thoracolumbar scoliosis. PMID- 26882858 TI - The relationship between back pain and schoolbag use: a cross-sectional study of 5,318 Italian students. AB - BACKGROUND CONTEXT: Back pain at a young age is considered to be predictive of chronicity. Several studies have investigated the relationship between the use of a schoolbag and back pain, although some aspects are still unclear. PURPOSE: The aim of this study was to evaluate back pain due to schoolbag use in terms of (1) prevalence and intensity, (2) differences between male and female pupils, and (3) predisposing factors. STUDY DESIGN: This is a cross-sectional study. PATIENT SAMPLE: The sample was composed of 5,318 healthy pupils aged 6 to 19 years (classified according to three age groups: children, younger adolescents, and older adolescents). OUTCOME MEASURES: Schoolbag-related pain was assessed by means of an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale. METHODS: Subjects underwent a face-to-face interview using an ad hoc questionnaire. The intensity of pain was assessed using the Wong scale. On the basis of the prevalence and intensity of back pain, we divided our population into two groups: (1) no or mild pain group and (2) moderate or severe pain group. The "schoolbag load" (ratio between schoolbag and pupil weight multiplied by 100) was calculated for each subject. RESULTS: More than 60% of the subjects reported pain. Although the schoolbag load decreased from children to young and older adolescents, schoolbag-related pain significantly increased (p<.001). Girls reported significantly more frequent and more severe pain than boys. The logistic model confirmed that adolescent girls are the group at greatest risk of suffering from intense pain. The schoolbag load had a weak impact on back pain, whereas the schoolbag carrying time was a strong predictor. CONCLUSIONS: Adolescent girls have the highest risk of experiencing severe back pain, regardless of schoolbag load. This suggests that other factors (anatomical, physiological, or environmental) might play an important role in pain perception. These aspects should be investigated to plan appropriate preventive and rehabilitative strategies. PMID- 26882860 TI - Renal cell carcinoma metastasis presenting as an osteosarcoma. PMID- 26882861 TI - Acute cauda equina syndrome secondary to chondromyxoid fibroma of the lumbar spine. PMID- 26882862 TI - Decreased expression of the type III TGF-beta receptor enhances metastasis and invasion in hepatocellullar carcinoma progression. AB - The transforming growth factor beta (TGF-beta) superfamily of cytokines is multifunctional and involved in the regulation of cell growth and differentiation. TGF-beta can induce an epithelial-mesenchymal transition (EMT) of both epithelial and endothelial cells. This has consequences for cancer progression in regards to both migration and invasion abilities. The type III TGF beta receptor (TbetaRIII) is a ubiquitously expressed TGF-beta co-receptor which regulates TGF-beta signaling and the progression of various types of cancer. Previous studies have shown that TbetaRIII exhibits abnormal expression and plays an essential role in regulating cancer invasion and metastasis, while little is known in regards to its role in hepatocellular carcinoma (HCC) progression. In the present study, we designed the present research to study the role of TbetaRIII in the invasion and metastasis of HCC and the possible mechanisms involved. The results demonstrated decreased expression of TbetaRIII in HCC patient tissues and human HCC cell lines. TGF-beta1 stimulation led to the increased migratory ability and reduced expression of TbetaRIII in HCC cells. In addition, knockdown of TbetaRIII by small interfering RNA (siRNA) promoted the migration and invasion of HCC cells and induced activation of the Smad2 and Akt pathways. All the results suggest that TbetaRIII is a novel suppressor of HCC progression. PMID- 26882863 TI - All-in-one: a versatile gas sensor based on fiber enhanced Raman spectroscopy for monitoring postharvest fruit conservation and ripening. AB - In today's fruit conservation rooms the ripening of harvested fruit is delayed by precise management of the interior oxygen (O2) and carbon dioxide (CO2) levels. Ethylene (C2H4), a natural plant hormone, is commonly used to trigger fruit ripening shortly before entering the market. Monitoring of these critical process gases, also of the increasingly favored cooling agent ammonia (NH3), is a crucial task in modern postharvest fruit management. The goal of this work was to develop and characterize a gas sensor setup based on fiber enhanced Raman spectroscopy for fast (time resolution of a few minutes) and non-destructive process gas monitoring throughout the complete postharvest production chain encompassing storage and transport in fruit conservation chambers as well as commercial fruit ripening in industrial ripening rooms. Exploiting a micro-structured hollow-core photonic crystal fiber for analyte gas confinement and sensitivity enhancement, the sensor features simultaneous quantification of O2, CO2, NH3 and C2H4 without cross-sensitivity in just one single measurement. Laboratory measurements of typical fruit conservation gas mixtures showed that the sensor is capable of quantifying O2 and CO2 concentration levels with accuracy of 3% or less with respect to reference concentrations. The sensor detected ammonia concentrations, relevant for chemical alarm purposes. Due to the high spectral resolution of the gas sensor, ethylene could be quantified simultaneously with O2 and CO2 in a multi-component mixture. These results indicate that fiber enhanced Raman sensors have a potential to become universally usable on-site gas sensors for controlled atmosphere applications in postharvest fruit management. PMID- 26882864 TI - Light intensity affects the uptake and metabolism of glycine by pakchoi (Brassica chinensis L.). AB - The uptake of glycine by pakchoi (Brassica chinensis L.), when supplied as single N-source or in a mixture of glycine and inorganic N, was studied at different light intensities under sterile conditions. At the optimal intensity (414 MUmol m(-2) s(-1)) for plant growth, glycine, nitrate, and ammonium contributed 29.4%, 39.5%, and 31.1% shoot N, respectively, and light intensity altered the preferential absorption of N sources. The lower (15)N-nitrate in root but higher in shoot and the higher (15)N-glycine in root but lower in shoot suggested that most (15)N-nitrate uptake by root transported to shoot rapidly, with the shoot being important for nitrate assimilation, and the N contribution of glycine was limited by post-uptake metabolism. The amount of glycine that was taken up by the plant was likely limited by root uptake at low light intensities and by the metabolism of ammonium produced by glycine at high light intensities. These results indicate that pakchoi has the ability to uptake a large quantity of glycine, but that uptake is strongly regulated by light intensity, with metabolism in the root inhibiting its N contribution. PMID- 26882865 TI - Functionalized Thallium Antimony Films as Excellent Candidates for Large-Gap Quantum Spin Hall Insulator. AB - Group III-V films are of great importance for their potential application in spintronics and quantum computing. Search for two-dimensional III-V films with a nontrivial large-gap are quite crucial for the realization of dissipationless transport edge channels using quantum spin Hall (QSH) effects. Here we use first principles calculations to predict a class of large-gap QSH insulators in functionalized TlSb monolayers (TlSbX2; (X = H, F, Cl, Br, I)), with sizable bulk gaps as large as 0.22~0.40 eV. The QSH state is identified by Z2 topological invariant together with helical edge states induced by spin-orbit coupling (SOC). Noticeably, the inverted band gap in the nontrivial states can be effectively tuned by the electric field and strain. Additionally, these films on BN substrate also maintain a nontrivial QSH state, which harbors a Dirac cone lying within the band gap. These findings may shed new light in future design and fabrication of QSH insulators based on two-dimensional honeycomb lattices in spintronics. PMID- 26882866 TI - Estimation of retorted phosphor powder from spent fluorescent lamps by thermal process. AB - The degree of thermal stabilization of phosphor powder from spent fluorescent lamps (SFLs) manufactured by three companies (A, B, C) was estimated by examining mercury content in phosphor powder with retorting time, retorting temperature and rotational speed of drum. Mercury content of phosphor powders from spent fluorescent lamps manufactured by A, B and C companies as samples in thermal experiments was 4031 mg/kg, 3522 mg/kg and 3172 mg/kg, respectively. In the thermal experiments, the optimal conditions for retorting time, retorting temperature, and rotational speed were determined at 6h, 400 degrees C, and 2.0 rpm, respectively. With thermal processing at the optimal conditions, mercury content of all samples for retorted phosphor powder was less than 3.0mg/kg, while efficiency of thermal process to control mercury content was higher than 99.9%. Leaching tests such as Toxicity Characteristic Leaching Procedure (TCLP) and Korea Extraction Test (KET) were subsequently carried out to verify if retorted phosphor powder is hazardous waste. Leaching concentrations of mercury for all samples of retorted phosphor powder were satisfied with regulatory levels in both leaching tests. Hence, retorted phosphor powders at the optimal conditions are considered to be non-hazardous wastes. PMID- 26882867 TI - The generation and cost of litter resulting from the curbside collection of recycling. AB - This study examined the generation of litter, defined as spillage and uncollected residue, from a curbside collection system for residential recycling. The primary recycling containers used in the study were 18-gal (68 L), open-top bins. The study, conducted over a seven-week period, was comprised of both an urban and suburban area. Six litter characterizations were conducted in which all new litter larger than 1 in.(2) was collected, segregated, counted, and weighed. We found that each week the open-top recycling bins contributed approximately 20,590 pieces of litter over 1 in. in size per every 1000 households, which resulted in the generation of 3.74 tons of litter per 1000 households per year. In addition to the bins having no top, the primary root causes of the litter were constantly overflowing recycling bins, the method of collection, and material scavenging. Based on an estimated cost of litter cleanup ranging from $0.17 to $0.79 per piece of litter, the direct economic costs from the collection of litter and loss in recycling revenues were estimated at US$3920 to US$19,250 per 1000 households per year. Other notable impacts from the litter, such as increased risk of flood damage from storm drain impairment and marine ecosystem damages exist, but were not monetized. The results strongly suggest that modification of the curbside collection system would decrease the amount and associated cost of litter by replacing existing curbside collection containers with larger volume containers with covers and by modifying the task-based incentive system to emphasize litter prevention rather than the current aim of completing the task most quickly. PMID- 26882868 TI - Ultrasonographic mound height as predictor of vesicoureteral reflux resolution after endoscopic treatment in children. AB - PURPOSE: Endoscopic dextranomer/hyaluronic acid copolymer (Dx/HA) injection is a safe and efficacious treatment option for vesicoureteral reflux (VUR) in children. Endoscopic appearance, hydrodistention and amount of injected Dx/HA have been demonstrated not to be reliable predictors of outcome. Aim of this study was to evaluate Dx/HA mounds on ultrasound scans (US) and find out any eventual correlation with reflux resolution. METHODS: We selected patients treated with endoscopic injection for moderate to high VUR, renal scaring or repeated infections under antibiotic prophylaxis. Success was defined by absence of VUR at control 3months after surgery; at 3months we also measured mound height ultrasonographically. RESULTS: We considered a total of 32 children (15 male, 17 female; 53 ureters) with a median age of 3years (+/-24months). Overall success rate was 77% per ureter. Success rate correlates directly with age and inversely with VUR grade. Mound height is the major predictive parameter for reflux resolution (sensitivity 100%, specificity 65.9%); mean mound heights of success group vs. persistence-of-reflux group were 9.97+/-1.61mm and 7.29+/-1.74mm respectively (p<0.0005). CONCLUSION: A mound measuring at least 9.8mm at post operative US scan is a predictor of reflux resolution. Age and grade also seems to influence success rate. PMID- 26882869 TI - Factors associated with failure of nonoperative treatment of complicated appendicitis in children. AB - Appendicitis remains the most common cause for emergency abdominal surgery in children. Immediate appendectomy in complicated, perforated appendicitis can be hazardous and nonoperative therapy has been gaining use as an initial therapy in children. Previous studies have reported failure rates in nonoperative therapy in such cases ranging from 10% to 41%. Factors leading to treatment failures have been studied with various and disparate results. We reviewed our institutional experience in treated complicated appendicitis, with focus on those initially managed nonoperatively. METHODS: Records of all children admitted with the diagnosis of perforated appendicitis to NYU Langone Medical Center and Bellevue Hospital Center from January 1, 2003 to December 31, 2013 were reviewed. The diagnosis was made with ultrasound and/or computed tomography scan. Those with abscesses amenable to drainage underwent aspiration and drain placement by an interventional radiologist. Broad spectrum intravenous (IV) antibiotics were given until the patient became afebrile, pain free and tolerating a regular diet. Oral antibiotics were continued for an additional week and interval appendectomy was done eight weeks later. The primary outcome measure was treatment response with failure defined as those who did not improve or required readmission for additional IV antibiotics and/or early appendectomy. Multiple patient and treatment related variables, including those previously reported as predicting failure in nonoperative therapy, were studied. Continuous variables were reported as means +/- standard error and compared using 2-tailed unpaired t tests; nonparametric variables were analyzed by Mann-Whitney U tests. Categorical variables were reported as medians +/- interquartile ranges and compared using Chi-square testing. Statistical significance was accepted for p<.05. RESULTS: Sixty-four patients were identified as undergoing initial nonoperative therapy. Fifty-two (81%) were categorized as treatment successes being treated nonoperatively and 12 (19%) were failures. Variables showing no significance in predicting treatment failures included duration of symptoms, presence of appendicolith, presence of phlegmon, presence of abscess, initial white blood cell count, and SIRS (Systemic Inflammatory Response Syndrome) positive. The variables that predicted failure of nonoperative therapy vs. successes were presence of bandemia (75% vs. 40%, p=0.052) and small bowel obstruction on imaging (42% vs. 15%, p=0.052) and presence of bandemia >=15% which was highly predictive of failure (67% vs. 4%, p<0.01). CONCLUSIONS: Predicting which patients with complicated perforated appendicitis will respond well to nonoperative therapy may allow us to more effectively treat patients with complicated perforated appendicitis. In our study the presence of small bowel obstruction and bandemia, especially >=15% correlated with treatment failure; this suggests that these select patients may need a modified treatment strategy. PMID- 26882870 TI - Protective effects of Chaenomeles thibetica extract against carbon tetrachloride induced damage via the MAPK/Nrf2 pathway. AB - Chaenomeles thibetica, a type of fruit of the genus Chaenomeles, is commonly cultivated and used as Mugua in China and as liquor, candy, and functional food in Tibet. Total phenol, flavonoid, and proanthocyanidin contents were measured in C. thibetica extract (CTE). CTE had a positive effect on free radical scavenging and anti-lipid oxidation in vitro. The protective effects of CTE against carbon tetrachloride (CCl4)-induced oxidative damage in vivo were also measured. The results of antioxidative enzymes indicated that CTE can increase the activities of the catalase, superoxide dismutase, and glutathione contents and reduce the level of malondialdehyde in rats. The levels of alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and total bilirubin were significantly reversed by CTE compared with the elevated levels in the CCl4 group. Besides, CTE could reverse the cell viability of HepG2 inoculated with CCl4via phosphorylation of mitogen-activated protein kinases (MAPKs), activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increasing the expression of phase II detoxification enzymes. These effects may expand the applications of C. thibetica and offer alternative food with antioxidant and hepatoprotective functions in the food industry. PMID- 26882872 TI - Healthcare policy in Africa: institutions and politics from colonialism to the present. PMID- 26882871 TI - Contribution of Walking to School to Individual and Population Moderate-Vigorous Intensity Physical Activity: Systematic Review and Meta-Analysis. AB - PURPOSE: This study estimated the contribution of walking to/from school to objectively measured daily moderate-vigorous intensity physical activity (MVPA) in individuals and populations. METHODS: MEDLINE, PsycINFO and SPORTDiscus were systematically searched up to February 2015. Two reviewers independently screened titles/abstracts/full-text articles, and assessed study quality. RESULTS: Of 2430 records, 129 were eligible for full-text screening. Twelve studies met the inclusion criteria of reporting objectively obtained measures of MVPA (total and while walking to/from school) in children and adolescents. The weighted mean MVPA accumulated in walking to and from school was 17 min/day in primary school pupils (9 samples, n = 3422) and 13 min/day in high school pupils (4 samples, n = 2600). Pooled analysis suggested that walking to and from school contributed 23% and 36% of MVPA on schooldays in primary school age children and high school pupils, respectively. All included studies were of high methodological quality. CONCLUSIONS: Walking to and from school makes a meaningful contribution to individual schoolday MVPA for active commuters in western countries. Since schooldays represent only around half of all days, and prevalence of walking to school is low in many countries, the contribution of walking to school to population MVPA is probably low. PMID- 26882874 TI - Neuropeptidase activities in plasma after acute restraint stress. Interaction with cortico-limbic areas. AB - OBJECTIVE: To evaluate the influence of acute restraint stress (ARS) on plasma enkephalinase and oxytocinase activities. ARS modifies basal activities in cortico-limbic regions of rats and induces changes in the correlations observed between these regions. The interactions between plasma and cortico-limbic activities will be also evaluated. METHODS: Enkephalinase (AlaAP and LeuAP) and oxytocinase (P-LeuAP) activities were fluorometrically determined in plasma of control and stressed rats using aminoacyl-beta-naphthylamides (aaNNap), AlaNNap and LeuNNap as substrates. RESULTS: No differences in enzymatic activities were observed between control and stressed animals in plasma. In contrast, highly significant positive and negative correlations between plasma and cortico-limbic regions were demonstrated in controls. Stress conditions significantly alter the pattern of these correlations. CONCLUSION: The present results clearly support a connection between plasma and brain involving certain neuropeptidase activities that change under stress conditions. PMID- 26882875 TI - Organo-Zintl Clusters [P7R4]: A New Class of Superalkalis. AB - Zintl ions composed of Group 13, 14, and 15 elements are multiply charged cluster anions that form the building blocks of the Zintl phase. Superalkalis, on the other hand, are cationic clusters that mimic the chemistry of the alkali atoms. It is, therefore, counterintuitive to expect that Zintl anions can be used as a core to construct superalkalis. In this paper, using density functional theory, we show that this is indeed possible. The results are compared with calculations at the MP2 level of theory. A systematic study of a P7(3-) Zintl core decorated with organic ligands [R = Me, CH2Me, CH(Me)2 and C(Me)3] shows that the ionization energies of some of the P7R4 species are smaller than those of the alkali atoms and hence can be classified as superalkalis. This opens the door to the design and synthesis of a new class of superalkali moieties apart from the traditional ones composed of only inorganic elements. PMID- 26882873 TI - Gpr176 is a Gz-linked orphan G-protein-coupled receptor that sets the pace of circadian behaviour. AB - G-protein-coupled receptors (GPCRs) participate in a broad range of physiological functions. A priority for fundamental and clinical research, therefore, is to decipher the function of over 140 remaining orphan GPCRs. The suprachiasmatic nucleus (SCN), the brain's circadian pacemaker, governs daily rhythms in behaviour and physiology. Here we launch the SCN orphan GPCR project to (i) search for murine orphan GPCRs with enriched expression in the SCN, (ii) generate mutant animals deficient in candidate GPCRs, and (iii) analyse the impact on circadian rhythms. We thereby identify Gpr176 as an SCN-enriched orphan GPCR that sets the pace of circadian behaviour. Gpr176 is expressed in a circadian manner by SCN neurons, and molecular characterization reveals that it represses cAMP signalling in an agonist-independent manner. Gpr176 acts independently of, and in parallel to, the Vipr2 GPCR, not through the canonical Gi, but via the unique G protein subclass Gz. PMID- 26882878 TI - Alcoholic liver disease: Mucosal microbes exacerbate experimental alcoholic steatohepatitis. PMID- 26882876 TI - Abdominal obesity is strongly associated with Cardiovascular Disease and its Risk Factors in Elderly and very Elderly Community-dwelling Chinese. AB - Obesity is usually considered to predispose to atherosclerotic cardiovascular disease (ASCVD) but milder degrees of obesity or overweight may be protective in some elderly populations. We examined the relationships between general and abdominal obesity indices with ASCVD and its risk factors in elderly (aged >= 65 years) Shanghai community residents Among the 3950 participants, 21.5% had ASCVD, 56.2% had body mass index (BMI) >= 24 kg/m2, 50.1% had high waist circumference (WC) and 77.1% had waist-to-height ratio (WHtR) >= 0.50. WHtR increased with age in both men and women whereas WC increased with age only in women and BMI decreased with age only in men. The optimal WHtR cut-off value to predict the risk of ASCVD determined by receiver operating characteristic analysis was WHtR >= 0.53 with a prevalence of 55.8%. Having abdominal obesity was significantly associated with prevalent ASCVD with WHtR >= 0.53 having a higher value for the odds ratio than high WC, whereas high BMI was not associated. All three indices predicted high glucose, triglycerides and hsCRP levels but only the WHtR >= 0.53 showed a significant association with physical activity. Abdominal obesity indices, but not BMI, predicted prevalent ASCVD and its risk factors in this elderly Chinese population. PMID- 26882879 TI - PPIs alter gut microbiota composition. PMID- 26882883 TI - New entry pathway for HCV. PMID- 26882884 TI - Stem cells: HSCT for Crohn's disease: work in progress or a bridge too far? PMID- 26882885 TI - Viral hepatitis: Drug-drug interactions in HCV treatment--the good, the bad and the ugly. PMID- 26882881 TI - Laparoscopic pancreatic surgery for benign and malignant disease. AB - Laparoscopic surgery for benign and malignant pancreatic lesions has slowly been gaining acceptance over the past decade and is being introduced in many centres. Some studies suggest that this approach is equivalent to or better than open surgery, but randomized data are needed to assess outcomes. In this Review, we aim to provide a comprehensive overview of the state of the art in laparoscopic pancreatic surgery by aggregating high-quality published evidence. Various aspects, including the benefits, limitations, oncological efficacy, learning curve and latest innovations, are discussed. The focus is on laparoscopic Whipple procedure and laparoscopic distal pancreatectomy for both benign and malignant disease, but robot-assisted surgery is also addressed. Surgical and oncological outcomes are discussed as well as quality of life parameters and the cost efficiency of laparoscopic pancreatic surgery. We have also included decision-aid algorithms based on the literature and our own expertise; these algorithms can assist in the decision to perform a laparoscopic or open procedure. PMID- 26882886 TI - Gut microbiota: Microbiota promote gut healing. PMID- 26882889 TI - Desert dust induces TLR signaling to trigger Th2-dominant lung allergic inflammation via a MyD88-dependent signaling pathway. AB - Asian sand dust (ASD) is known to exacerbate asthma, although its mechanism is not yet well understood. In this study, when the effects on inflammatory response by LPS present in ASD was investigated by measuring the gene expression of cytokines and chemokines in RAW264.7 cells treated with ASD and/or polymyxin B (PMB), the ASD effects were attenuated by PMB, but not completely. When an in vitro study was performed using bone marrow-derived macrophages (BMDMs) from WT, TLR2(-/-), TLR4(-/-), and MyD88(-/-) BALB/c mice and BMDMs from WT, TLR2(-/-), TLR4(-/-), TLR2/4(-/-), TLR7/9(-/-), and MyD88(-/-) C57BL/6J mice, cytokine (IL 6, IL-12) production in BMDMs was higher in ASD-stimulated TLR2(-/-) cells than in TLR4(-/-) cells, whereas it was lower or undetectable in TLR2/4(-/-) and MyD88(-/-) cells. These results suggest that ASD causes cytokine production predominantly in a TLR4/MyD88-dependent pathway. When WT and TLRs 2(-/-), 4(-/-), and MyD88(-/-) BALB/c mice were intratracheally challenged with OVA and/or ASD, ASD caused exacerbation of lung eosinophilia along with Th2 cytokine and eosinophil-relevant chemokine production. Serum OVA-specific IgE and IgG1 similar to WT was observed in TLRs 2(-/-), 4(-/-) mice, but not in MyD88(-/-) mice. The Th2 responses in TLR2(-/-) mice were attenuated remarkably by PMB. These results indicate that ASD exacerbates lung eosinophilia in a MyD88-dependent pathway. TLRs 2 and 4 signaling may be important in the increase in lung eosinophilia. Also, the TLR4 ligand LPS and TLR2 ligand like beta-glucan may be strong candidates for exacerbation of lung eosinophilia. PMID- 26882891 TI - Peer-Delivered Recovery Support Services for Addictions in the United States: A Systematic Review. AB - This systematic review identifies, appraises, and summarizes the evidence on the effectiveness of peer-delivered recovery support services for people in recovery from alcohol and drug addiction. Nine studies met criteria for inclusion in the review. They were assessed for quality and outcomes including substance use and recovery-related factors. Despite significant methodological limitations found in the included studies, the body of evidence suggests salutary effects on participants. Current limitations and recommendations for future research are discussed. PMID- 26882890 TI - Exposure to salient, dynamic sensory stimuli during development increases distractibility in adulthood. AB - It has been suggested that excessive exposure of children to the dynamic and highly salient audio-visual stimuli conveyed by electronic media may induce attention-related deficits in adulthood. This study was designed to evaluate this hypothesis in a controlled animal model setup. Building on their natural responsiveness to odors, we exposed juvenile rats for 1 h daily to a dynamic series of interchanging, highly salient odors, while controls were exposed to a non-changing mixture of these odors. Upon reaching adulthood, we tested the attentional capacity of the rats and measured their brain-derived neurotrophic factor (BDNF) levels as a proxy of neuronal plasticity. As compared with controls, rats exposed to the dynamic stimulation showed no attentional deficits under baseline task conditions, but their performance was dramatically impaired when an auditory distractor was introduced in the task. In addition, BDNF levels in the dorsal striatum of these rats were significantly increased relative to controls. These findings provide first empirical evidence that a continuous exposure to dynamic, highly salient stimuli has long-term effects on attentional functions later in life, and that these effects may have neural correlates in the dorsal striatum. PMID- 26882892 TI - Analysis of root-knot nematode and fusarium wilt disease resistance in cotton (Gossypium spp.) using chromosome substitution lines from two alien species. AB - Chromosome substitution (CS) lines in plants are a powerful genetic resource for analyzing the contribution of chromosome segments to phenotypic variance. In this study, a series of interspecific cotton (Gossypium spp.) CS lines were used to identify a new germplasm resource, and to validate chromosomal regions and favorable alleles associated with nematode or fungal disease resistance traits. The CS lines were developed in the G. hirsutum L. TM-1 background with chromosome or chromosome segment substitutions from G. barbadense L. Pima 3-79 or G. tomentosum. Root-knot nematode (Meloidogyne incognita) and fusarium wilt (Fusarium oxysporum f. sp. vasinfectum) (races 1 and 4) resistance alleles and quantitative trait loci (QTL) previously placed on cotton chromosomes using SSR markers in two interspecific recombinant inbred line populations were chosen for testing. Phenotypic responses of increased resistance or susceptibility in controlled inoculation and infested field assays confirmed the resistance QTLs, based on substitution with the positive or negative allele for resistance. Lines CS-B22Lo, CS-B04, and CS-B18 showed high resistance to nematode root-galling, confirming QTLs on chromosomes 4 and 22 (long arm) with resistance alleles from Pima 3-79. Line CS-B16 had less fusarium race 1-induced vascular root staining and higher percent survival than the TM-1 parent, confirming a major resistance QTL on chromosome 16. Lines CS-B(17-11) and CS-B17 had high fusarium race 4 vascular symptoms and low survival due to susceptible alleles introgressed from Pima 3-79, confirming the localization on chromosome 17 of an identified QTL with resistance alleles from TM1 and other resistant lines. Analyses validated regions on chromosomes 11, 16, and 17 harboring nematode and fusarium wilt resistance genes and demonstrated the value of CS lines as both a germplasm resource for breeding programs and as a powerful genetic analysis tool for determining QTL effects for disease resistance. CS lines carrying small alien chromosome segments with favorable QTL alleles could be used for effective introgression of biotic stress resistance or many other desirable traits by targeting gene interactions and reducing linkage drag effects. PMID- 26882893 TI - Saccharopolyspora subtropica sp. nov., a thermophilic actinomycete isolated from soil of a sugar cane field. AB - A novel thermophilic actinomycete, designated strain T3T, was isolated from a soil sample of a sugar cane field. The strain grew at 25-60 degrees C (optimum 37-50 degrees C), at pH 6.0-11.0 (optimum 7.0-9.0) and with 0-12.0 % (w/v) NaCl (optimum 0-7 %). The aerial mycelium was white and the vegetative mycelium was colourless to pale yellow. The substrate mycelium fragmented into rod-shaped elements after 4-5 days at 50 degrees C. The aerial mycelium formed flexuous chains of 5-20 spores per chain; the oval-shaped spores had spiny surfaces and were non-motile. The organism contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars consisted of arabinose, galactose and ribose. The cellular fatty acid profile consisted mainly of anteiso-C17 : 0, iso-C17 : 0 and iso-C16 : 0. The quinone system was composed predominantly of MK-9(H4). The phospholipids detected were diphosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylmethylethanolamine and ninhydrin-positive glycophospholipids. The DNA G+C content of strain T3T was 71.3 mol%. The organism showed a combination of morphological and chemotaxonomic properties typical of members of the genus Saccharopolyspora. In the 16S rRNA gene tree of Saccharopolyspora it formed a distinct phyletic line and was related most closely to Saccharopolyspora thermophila 216T. However, the phenotypic characteristics of strain T3T were significantly different from those of S. thermophila 216T and DNA DNA hybridization revealed a low level of relatedness (28.6-32.3 %) between them. Based on the phenotypic and phylogenetic data, strain T3T represents a novel species in the genus Saccharopolyspora, for which the name Saccharopolyspora subtropica sp. nov. is proposed. The type strain is T3T ( = DSM 46801T = CGMCC 4.7206T). PMID- 26882894 TI - Post graduate clinical placements: evaluating benefits and challenges with a mixed methods cross sectional design. AB - BACKGROUND: Systematic evaluations of clinical placements are rare, especially when offered alongside academic postgraduate courses. An evidence-based approach is important to allow pedagogically-driven provision, rather than that solely governed by opinion or market demand. Our evaluation assessed a voluntary clinical placement scheme allied to a mental health course. METHODS: Data were collected over academic years 2010/11- 2013/14, from participating students (n = 20 to 58) and clinician supervisors (n = 10-12), using a mixed-methods cross sectional design. Quantitative evaluation captured information on uptake, dropout, resource use, attitudes and experience, using standardized (the Placement Evaluation Questionnaire; the Scale To Assess the Therapeutic Relationship - Clinical version and the University of Toronto Placement Supervisor Evaluation) and bespoke questionnaires and audit data. Qualitative evaluation comprised two focus groups (5 clinicians, 5 students), to investigate attitudes, experience, perceived benefits, disadvantages and desired future developments. Data were analysed using framework analysis to identify a priori and emergent themes. RESULTS: High uptake (around 70 placements per annum), low dropout (2-3 students per annum; 5 %) and positive focus group comments suggested placements successfully provided added value and catered sufficiently to student demand. Students' responses confirmed that placements met expectations and the perception of benefit remained after completion with 70 % (n = 14) reporting an overall positive experience, 75 % (n = 15) reporting a pleasant learning experience, 60 % (n = 12) feeling that their clinical skills were enhanced and 85 % (n = 17) believing that it would benefit other students. Placements contributed the equivalent of seven full time unskilled posts per annum to local health care services. While qualitative data revealed perceived 'mutual benefit' for both students and clinicians, this was qualified by the inherent limitations of students' time and expertise. Areas for development included fostering learning around professionalism and students' confidence on placement. CONCLUSIONS: The addition of healthcare placements to academic postgraduate taught courses can improve their attractiveness to applicants, benefit healthcare services and enhance students' perception of their learning experiences. Well-positioned and supported placement learning opportunities could become a key differentiator for academic courses, over potential competitors. However, the actual implications for student employability and achievement remain to be established. PMID- 26882895 TI - Impact of clinically tested NEP/ACE inhibitors on tumor uptake of [(111)In DOTA]MG11-first estimates for clinical translation. AB - BACKGROUND: We have recently shown that treatment of mice with the neutral endopeptidase (NEP) inhibitor phosphoramidon (PA) improves the bioavailability and tumor uptake of biodegradable radiopeptides. For the truncated gastrin radiotracer [(111)In-DOTA]MG11 ([(DOTA)DGlu(10)]gastrin(10-17)), this method led to impressively high tumor-to-kidney ratios. Translation of this concept in the clinic requires the use of certified NEP inhibitors, such as thiorphan (TO) and its orally administered prodrug racecadotril (Race). Besides NEP, angiotensin converting enzyme (ACE) has also been implicated in the catabolism of gastrin analogs. In the present study, we first compared the effects induced by NEP inhibition (using PA, TO, or Race) and/or by ACE inhibition (using lisinopril, Lis) on the biodistribution profile of [(111)In-DOTA]MG11 in mice. In addition, we compared the efficacy of PA and TO at different administered doses to enhance tumor uptake. METHODS: [(111)In-DOTA]MG11 was coinjected with (a) vehicle, (b) PA (300 MUg), (c) TO (150 MUg), (d) Lis (100 MUg), (e) PA (300 MUg) plus Lis (100 MUg), or (f) 30-40 min after intraperitoneal (ip) injection of Race (3 mg) in SCID mice bearing AR42J xenografts. In addition, [(111)In-DOTA]MG11 was coinjected with vehicle, or with progressively increasing amounts of PA (3, 30, or 300 MUg) or TO (1.5, 15, and 150 MUg) in SCID mice bearing twin A431-CCK2R(+/ ) tumors. In all above cases, biodistribution was conducted at 4 h postinjection (pi). RESULTS: During NEP inhibition, the uptake of [(111)In-DOTA]MG11 in the AR42J tumors impressively increased from 1.8 +/- 1.0 % ID/g (controls) to 15.3 +/ 4.7 % ID/g (PA) and 12.3 +/- 3.6 % ID/g (TO), while with Race tumor values reached 6.8 +/- 2.8 % ID/g. Conversely, Lis had no effect on tumor uptake and no additive effect when coinjected with PA. During the dose dependence study in mice, PA turned out to be more efficacious in enhancing tumor uptake of [(111)In DOTA]MG11 in the CCK2R-positive tumors compared to equimolar amounts of TO. In all cases, renal accumulation remained low, resulting in notable increases of tumor-to-kidney ratios. CONCLUSIONS: This study has confirmed NEP as the predominant degrading enzyme of [(111)In-DOTA]MG11 and ruled out the involvement of ACE in the in vivo catabolism of the radiotracer. NEP inhibition with the clinically tested NEP inhibitors TO and Race resulted in significant enhancement of tumor-to-kidney ratios vs. CONTROLS: However, compared with PA, TO and its prodrug Race induced less potent increases of tumor uptake, highlighting the significance of inhibitor type, administration route, and dose for implementing a first proof-of-principle study in human. PMID- 26882896 TI - Cholelithiasis and complicated chronic pancreatitis mimicking malignancy. PMID- 26882897 TI - Physiological evidence for diversification of IFNalpha- and IFNbeta-mediated response programs in different autoimmune diseases. AB - BACKGROUND: Activation of the type I interferon (IFN) response program is described for several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), myositis (IIM) and rheumatoid arthritis (RA). While IFNalpha contributes to SLE pathology, IFNbeta therapy is often beneficial in MS, implying different immunoregulatory roles for these IFNs. This study was aimed to investigate potential diversification of IFNalpha-and IFNbeta-mediated response programs in autoimmune diseases. METHODS: Peripheral blood gene expression of 23 prototypical type I IFN response genes (IRGs) was determined in 54 healthy controls (HCs), 69 SLE (47 test, 22 validation), 149 IFNbeta-treated MS (71 test, 78 validation), 160 untreated MS, 78 IIM and 76 RA patients. Patients with a type I IFN signature were selected for analysis. RESULTS: We identified IFNalpha- and IFNbeta-specific response programs (GC-A and GC-B, respectively) in SLE and IFNbeta-treated MS patients. Concordantly, the GC-A/GC-B log-ratio was positive for all SLE patients and negative for virtually all IFNbeta-treated MS patients, which was confirmed in additional cohorts. Applying this information to other autoimmune diseases, IIM patients displayed positive GC A/GC-B log-ratios, indicating predominant IFNalpha activity. The GC-A/GC-B log ratio in RA was lower and approached zero in part of the patients, implying relative importance of both clusters. Remarkably, GC-A/GC-B log-ratios appeared most heterogeneous in untreated MS; half of the patients displayed GC-A dominance, whereas others showed GC-B dominance or log-ratios near zero. CONCLUSIONS: Our findings show diversification of the type I IFN response in autoimmune diseases, suggesting different pathogenic roles of the type I IFNs. PMID- 26882898 TI - Molecular and cellular characteristics of hybrid vigour in a commercial hybrid of Chinese cabbage. AB - BACKGROUND: Heterosis or hybrid vigour is a phenomenon in which hybrid progeny exhibit superior performance compared to their parental inbred lines. Most commercial Chinese cabbage cultivars are F1 hybrids and their level of hybrid vigour is of critical importance and is a key selection criterion in the breeding system. RESULTS: We have characterized the heterotic phenotype of one F1 hybrid cultivar of Chinese cabbage and its parental lines from early- to late developmental stages of the plants. Hybrid cotyledons are larger than those of the parents at 4 days after sowing and biomass in the hybrid, determined by the fresh weight of leaves, is greater than that of the larger parent line by approximately 20% at 14 days after sowing. The final yield of the hybrid harvested at 63 days after sowing is 25% greater than the yield of the better parent. The larger leaves of the hybrid are a consequence of increased cell size and number of the photosynthetic palisade mesophyll cells and other leaf cells. The accumulation of plant hormones in the F1 was within the range of the parental levels at both 2 and 10 days after sowing. Two days after sowing, the expression levels of chloroplast-targeted genes in the cotyledon cells were upregulated in the F1 hybrid relative to their mid parent values. Shutdown of chlorophyll biosynthesis in the cotyledon by norflurazon prevented the increased leaf area in the F1 hybrid. CONCLUSIONS: In the cotyledons of F1 hybrids, chloroplast-targeted genes were upregulated at 2 days after sowing. The increased activity levels of this group of genes suggested that their differential transcription levels could be important for establishing early heterosis but the increased transcription levels were transient. Inhibition of the photosynthetic process in the cotyledon reduced heterosis in later seedling stages. These observations suggest early developmental events in the germinating seedling of the hybrid may be important for later developmental vigour and yield advantage. PMID- 26882900 TI - Irritable bowel syndrome-specific health-related quality of life instrument: development and psychometric evaluation. AB - BACKGROUND: Health-related quality of life (HRQOL) is an important outcome indicator for chronic disease, and particularly in the absence of biological markers for illness, such as with irritable bowel syndrome (IBS). The aims of this study were to develop and evaluate a new IBS-specific HRQOL instrument (IBS HR-QOL). METHODS: This methodological study comprised three steps: conceptualization of the IBS-HR-QOL, item extraction and establishment of content validity, and psychometric evaluation of the instrument with 267 IBS patients recruited from four university hospitals. RESULTS: The content validity of the developed IBS-HR-QOL was assessed by 11 experts. Exploratory and confirmatory factor analyses yielded four factors. The criterion and convergent validities of the IBS-HR-QOL were demonstrated using the Short Form-36 and the Hospital Anxiety and Depression Scale, respectively. Known-groups validity was demonstrated using a symptom-severity scale. The internal consistency reliability and test-retest reliability were satisfactory, with a Cronbach's alpha and intraclass correlation coefficient of 0.93 and 0.88, respectively. CONCLUSIONS: The IBS-HR-QOL comprises a total of 16 items. The IBS-HR-QOL demonstrated good psychometric properties. This instrument is easily comprehensible and short, rendering it feasible for use in clinical practice and research. PMID- 26882899 TI - Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy. AB - Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment. PMID- 26882901 TI - Ensuring the Health, Safety and Preparedness of U.S. Medical Students Participating in Global Health Electives Overseas. AB - Global health electives based in resource-poor countries have become extremely popular with medical students from resource rich ones. As the number of such programs and participants increase, so too do the absolute health and safety risks. It is clear from a number of published reports that many institutions provide little or no meaningful preparedness for students and do little to ensure their health and safety. These deficiencies together can affect students, their foreign hosts, and sponsoring institutions. The School of Public Health at the State University of New York, Downstate Medical Center, and its predecessor, the Department of Preventive Medicine and Community Health, have sponsored a 6-8 week global health elective for fourth year medical students since 1980. The purposes of this elective are to provide students with an opportunity to observe the health care and public health systems in resource-poor countries, provide medical service, and have a cross-cultural experience. Over the course of the past 35 years, 386 students have participated in this global health elective in more than 41 resource-poor countries. Recent annual applications for this elective have been as high as 44 out of a class of 200 students. Over the past 10 years, annual acceptance rates have varied, ranging from a low of 32 % in 2007-2008 to a high of 74 % in 2010-2011 and 2013-2014. Careful screening, including a written application, review of academic records and personal interviews, has resulted in the selection of highly mature, adaptable, and dedicated students who have performed well at overseas sites. Appropriately preparing students for an overseas global health experience in resource-poor countries requires the investment of much professional and staff time and effort. At the SUNY Downstate School of Public Health, these resources have underpinned our Global Health in Developing Countries elective for many years. As a result, the elective is characterized by meticulous organization, extensive preparedness measures for students, and continuous monitoring of site and country safety. The health of students is ensured by one-on-one assessment of immunization needs, anti malarials, and the provision of a five-day supply of post-exposure HIV prophylaxis. Students sign agreements regarding the legal issues, immunizations, and anti-malarials recommended as well as HIV post-exposure prophylaxis. They are also required to obtain medical evacuation insurance provided by the university, and medical care insurance valid overseas. Student travel plans are also approved as is in-country lodging. The focus of our 6-8 week global health elective is not clinical medicine. Rather, it is to enable students to learn about the health care and public health systems in a resource-poor country. Through that focus, they also come to understand the causes of health and health care disparities that exist in the country to which they are assigned. Our students are greatly advantaged with regard to cross-cultural understanding since our school is located in New York City's Borough of Brooklyn, where 40 % of the population was born outside of the U.S. Our comprehensive effort at risk management for this global health elective includes a thorough debriefing for each student upon his/her return. Special attention is given to ascertaining illness or injury while overseas, and, when necessary, immediate referral is made to an appropriate university clinical department where a student can be appropriately case managed. Meticulous oversight, careful selection of safe overseas sites, and attention to preparing students have resulted in significant risk reduction and successful experiences for the majority of our 386 students. This article describes the model we have developed for ensuring the health, safety, and preparedness of students participating in our global health elective. PMID- 26882902 TI - Bevacizumab for metachronous metastatic colorectal cancer: a reflection of community based practice. AB - BACKGROUND: Although the efficacy of bevacizumab has been established in patients with metastatic colorectal cancer (mCRC), population-based studies are needed to gain insight into the actual implementation of bevacizumab in daily practice. Since these studies are lacking for patients with metachronous metastases, the aim of this study is to evaluate the current role of bevacizumab in the treatment of metachronous metastases of CRC. METHODS: Data on the use of bevacizumab as palliative treatment of metachronous metastases were collected for patients diagnosed with M0 CRC between 2003 and 2008 in the Eindhoven Cancer Registry (n = 361). Median follow up was 5.3 years. RESULTS: One hundred eighty-five patients received bevacizumab in addition to first-line palliative chemotherapy (51%), ranging from 36% to 80% between hospitals of diagnosis (p < 0.0001). Combined cytostatic regimens (CAPOX/FOLFOX in 97%) were prescribed in the majority of patients (63%) and were associated with a higher odds for additional treatment with bevacizumab than single-agent cytostatic regimens (OR 9.9, 95% CI 5.51 18.00). Median overall survival (OS) rates were 21.6 and 13.9 months with and without the addition of bevacizumab to palliative systemic treatment respectively (p < 0.0001). The addition of bevacizumab to palliative chemotherapy was associated with a reduced hazard ratio for death (HR 0.6, 95% CI 0.45-0.73) after adjustment for patient- and tumor characteristics and the prescribed chemotherapeutic regimen. CONCLUSION: Bevacizumab is adopted as a therapeutic option for metachronous metastasized CRC mainly in addition to first-line oxaliplatin-based regimens, and was associated with a reduced risk of death. The presence of inter-hospital differences in the prescription of bevacizumab reflected important differences in attitude and policies in clinical practice. Ongoing efforts should be made to further define the position of targeted agents in the treatment of metastatic colorectal cancer. PMID- 26882903 TI - Gadd45b prevents autophagy and apoptosis against rat cerebral neuron oxygen glucose deprivation/reperfusion injury. AB - Autophagic (type II) cell death has been suggested to play pathogenetic roles in cerebral ischemia. Growth arrest and DNA damage response 45b (Gadd45b) has been shown to protect against rat brain ischemia injury through inhibiting apoptosis. However, the relationship between Gadd45b and autophagy in cerebral ischemia/reperfusion (I/R) injury remains uncertain. The aim of this study is to investigate the effect of Gadd45b on autophagy. We adopt the oxygen-glucose deprivation and reperfusion (OGD/R) model of rat primary cortex neurons, and lentivirus interference used to silence Gadd45b expression. Cell viability and injury assay were performed using CCK-8 and LDH kit. Autophagy activation was monitored by expression of ATG5, LC3, Beclin-1, ATG7 and ATG3. Neuron apoptosis was monitored by expression of Bcl-2, Bax, cleaved caspase3, p53 and TUNEL assay. Neuron neurites were assayed by double immunofluorescent labeling with Tuj1 and LC3B. Here, we demonstrated that the expression of Gadd45b was strongly up regulated at 24 h after 3 h OGD treatment. ShRNA-Gadd45b increased the expression of autophagy related proteins, aggravated OGD/R-induced neuron cell apoptosis and neurites injury. ShRNA-Gadd45b co-treatment with autophagy inhibitor 3 methyladenine (3-MA) or Wortmannin partly inhibited the ratio of LC3II/LC3I, and slightly ameliorated neuron cell apoptosis under OGD/R. Furthermore, shRNA Gadd45b inhibited the p-p38 level involved in autophagy, but increased the p-JNK level involved in apoptosis. ShRNA-Gadd45b co-treatment with p38 inhibitor obviously induced autophagy. ShRNA-Gadd45b co-treatment with JNK inhibitor alleviated neuron cell apoptosis. In conclusion, our data suggested that Gadd45b inhibited autophagy and apoptosis under OGD/R. Gadd45b may be a common regulatory protein to control autophagy and apoptosis. PMID- 26882904 TI - [Not Available]. PMID- 26882905 TI - [Rehabilitation standards for follow-up treatment and rehabilitation of patients with ventricular assist device (VAD)]. AB - The increasing use of ventricular assist devices (VADs) in terminal heart failure patients provides new challenges to cardiac rehabilitation physicians. Structured cardiac rehabilitation strategies are still poorly implemented for this special patient group. Clear guidance and more evidence for optimal modalities are needed. Thereby, attention has to be paid to specific aspects, such as psychological and social support and education (e.g., device management, INR self management, drive-line care, and medication).In Germany, the post-implant treatment and rehabilitation of VAD Patients working group was founded in 2012. This working group has developed clear recommendations for the rehabilitation of VAD patients according to the available literature. All facets of VAD patients' rehabilitation are covered. The present paper is unique in Europe and represents a milestone to overcome the heterogeneity of VAD patient rehabilitation. PMID- 26882906 TI - Imaging of Abusive Trauma. AB - "Shaken baby syndrome" is a term often used by the physicians and public to describe abusive trauma inflicted on infants and young children. Advances in the understanding of the mechanisms and the associated clinical spectrum of injury has lead us to modify our terminology and address it as "abusive trauma" (AT). Pediatric abusive head trauma is defined as an injury to the skull or intracranial contents of an infant or a young child (< 5 y age) due to inflicted blunt impact and/or violent shaking. This chapter focuses on the imaging aspects of childhood abusive trauma along with a brief description of the mechanism and pathophysiology of abusive injury. The diagnosis of AT is not always obvious, and abusive injuries in many infants may remain unrecognized. Pediatricians should be cognizant of AT since pediatricians play a crucial role in the diagnosis, management and prevention of AT. PMID- 26882908 TI - Normal ranges and test-retest reproducibility of flow and velocity parameters in intracranial arteries measured with phase-contrast magnetic resonance imaging. AB - INTRODUCTION: The purpose of the present study was to investigate normal ranges and test-retest reproducibility of phase-contrast MRI (PC-MRI)-measured flow and velocity parameters in intracranial arteries. METHODS: Highest flow (HF), lowest flow (LF), peak systolic velocity (PSV), and end diastolic velocity (EDV) were measured at two dates in the anterior (ACA), middle (MCA), and posterior (PCA) cerebral arteries of 30 healthy volunteers using two-dimensional PC-MRI at 3 T. Least detectable difference (LDD) was calculated. RESULTS: In the left ACA, HF was (mean (range, LDD)) 126 ml/min (36-312, 59 %), LF 61 ml/min (0-156, 101 %), PSV 64 cm/s (32-141, 67 %), and EDV 35 cm/s (18-55, 42 %); in the right ACA, HF was 154 ml/min (42-246, 49 %), LF 77 ml/min (0-156, 131 %), PSV 75 cm/s (26-161, 82 %), and EDV 39 cm/s (7-59, 67 %). In the left MCA, HF was 235 ml/min (126-372, 35 %), LF 116 ml/min (42-186, 48 %), PSV 90 cm/s (55-183, 39 %), and EDV 46 cm/s (20-66, 28 %); in the right MCA, HF was 238 ml/min (162-342, 44 %), LF 120 ml/min (72-216, 48 %), PSV 88 cm/s (55-141, 35 %), and EDV 45 cm/s (26-67, 23 %). In the left PCA, HF was 108 ml/min (42-168, 54 %), LF 53 ml/min (18-108, 64 %), PSV 50 cm/s (24-77, 63 %), and EDV 28 cm/s (14-40, 45 %); in the right PCA, HF was 98 ml/min (30-162, 49 %), LF 49 ml/min (12-84, 55 %), PSV 47 cm/s (27-88, 59 %), and EDV 27 cm/s (16-41, 45 %). CONCLUSION: PC-MRI-measured flow and velocity parameters in the main intracranial arteries have large normal ranges. Reproducibility is highest in MCA. PMID- 26882909 TI - Abstinence at Successful Discharge in Publicly Funded Addiction Health Services. AB - Abstinence at successful discharge in substance use disorder treatment is important to reducing relapse rates and increasing long-term recovery from substance use disorders. However, few studies have examined abstinence as an essential component of successful discharge. This study examined rates and correlates of reported abstinence (nonuse of drugs 30 days prior to successful discharge) among clients attending publicly funded treatment in Los Angeles County, California. Finding show that only 36% of clients who were successfully discharged reported abstinence. Black clients were less likely than non-Hispanic Whites to report abstinence at successful discharge. Clients in methadone treatment programs were less likely than outpatient clients to report abstinence, whereas clients referred to treatment through the legal system (Proposition 36) were more likely to report abstinence compared to self-referred clients. Findings underscore the importance of systematic assessment of abstinence in determining successful discharge and provide a basis for further examination of strategies to improve abstinence and reduce relapse. PMID- 26882907 TI - Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer. AB - BACKGROUND: There is a need to improve prediction of response to chemotherapy in breast cancer in order to improve clinical management and this may be achieved by harnessing computational metrics of tissue pathology. We investigated the association between quantitative image metrics derived from computational analysis of digital pathology slides and response to chemotherapy in women with breast cancer who received neoadjuvant chemotherapy. METHODS: We digitised tissue sections of both diagnostic and surgical samples of breast tumours from 768 patients enrolled in the Neo-tAnGo randomized controlled trial. We subjected digital images to systematic analysis optimised for detection of single cells. Machine-learning methods were used to classify cells as cancer, stromal or lymphocyte and we computed estimates of absolute numbers, relative fractions and cell densities using these data. Pathological complete response (pCR), a histological indicator of chemotherapy response, was the primary endpoint. Fifteen image metrics were tested for their association with pCR using univariate and multivariate logistic regression. RESULTS: Median lymphocyte density proved most strongly associated with pCR on univariate analysis (OR 4.46, 95 % CI 2.34 8.50, p < 0.0001; observations = 614) and on multivariate analysis (OR 2.42, 95 % CI 1.08-5.40, p = 0.03; observations = 406) after adjustment for clinical factors. Further exploratory analyses revealed that in approximately one quarter of cases there was an increase in lymphocyte density in the tumour removed at surgery compared to diagnostic biopsies. A reduction in lymphocyte density at surgery was strongly associated with pCR (OR 0.28, 95 % CI 0.17-0.47, p < 0.0001; observations = 553). CONCLUSIONS: A data-driven analysis of computational pathology reveals lymphocyte density as an independent predictor of pCR. Paradoxically an increase in lymphocyte density, following exposure to chemotherapy, is associated with a lack of pCR. Computational pathology can provide objective, quantitative and reproducible tissue metrics and represents a viable means of outcome prediction in breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00070278 ; 03/10/2003. PMID- 26882911 TI - Of Deep Waters and Thin Air: Pulmonary Edema in Swimmers Versus Mountaineers. PMID- 26882910 TI - Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil. AB - BACKGROUND: Swimming-induced pulmonary edema (SIPE) occurs during swimming or scuba diving, often in young individuals with no predisposing conditions, and its pathophysiology is poorly understood. This study tested the hypothesis that pulmonary artery and pulmonary artery wedge pressures are higher in SIPE susceptible individuals during submerged exercise than in the general population and are reduced by sildenafil. METHODS AND RESULTS: Ten study subjects with a history of SIPE (mean age, 41.6 years) and 20 control subjects (mean age, 36.2 years) were instrumented with radial artery and pulmonary artery catheters and performed moderate cycle ergometer exercise for 6 to 7 minutes while submersed in 20 degrees C water. SIPE-susceptible subjects repeated the exercise 150 minutes after oral administration of 50 mg sildenafil. Work rate and mean arterial pressure during exercise were similar in controls and SIPE-susceptible subjects. Average o2 and cardiac output in controls and SIPE-susceptible subjects were: o2 2.42 L.min(-1) versus 1.95 L.min(-1), P=0.2; and cardiac output 17.9 L.min(-1) versus 13.8 L.min(-1), P=0.01. Accounting for differences in cardiac output between groups, mean pulmonary artery pressure at cardiac output=13.8 L.min(-1) was 22.5 mm Hg in controls versus 34.0 mm Hg in SIPE-susceptible subjects (P=0.004), and the corresponding pulmonary artery wedge pressure was 11.0 mm Hg versus 18.8 mm Hg (P=0.028). After sildenafil, there were no statistically significant differences in mean pulmonary artery pressure or pulmonary artery wedge pressure between SIPE-susceptible subjects and controls. CONCLUSIONS: These observations confirm that SIPE is a form of hemodynamic pulmonary edema. The reduction in pulmonary vascular pressures after sildenafil with no adverse effect on exercise hemodynamics suggests that it may be useful in SIPE prevention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00815646. PMID- 26882914 TI - 2016 European guideline on donovanosis. AB - Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic cases in Papua New Guinea, South Africa, India, Brazil and Australia. The causative organism is Calymmatobacterium granulomatis, though a proposal has been put forward that the organism be reclassified as Klebsiella granulomatis comb nov The incubation period is approximately 50 days with genital papules developing into ulcers that increase in size. Four types of lesions are described - ulcerogranulomatous, hypertrophic, necrotic and sclerotic. The diagnosis is usually confirmed by microscopic identification of characteristic Donovan bodies on stained tissue smears. More recently, polymerase chain reaction methods have been developed. The recommended treatment is azithromycin 1 g weekly until complete healing is achieved. PMID- 26882913 TI - Pharmacological agents used for treatment and prevention in noise-induced hearing loss. AB - Noise is a stress factor that causes auditory, psychological and physiological effects. The realization that sudden loud noises or chronic exposure to noise in social and working environments can cause hearing loss has led to increased interest in noise-induced hearing loss (NIHL). The best means of preventing primary damage is protection against noise. Since this protection is not always possible for various reasons, the use of pharmacological agents to prevent or treat NIHL should also be considered. The purpose of this study is to discuss current pharmacological protection and treatment options in the light of the literature, since no such extensive reviews have been performed to date, including agents used for protection against and treatment of NIHL. We reviewed both animal and clinical studies, and these are discussed separately for ease of comprehension. For each agent, first animal studies, then clinical studies, if available, are discussed. We also performed a two-step search of the literature. In the first step, we searched the terms "noise induced hearing loss", "treatment" and "protection" in Pubmed. Based on the results obtained, we identified the agents used for the treatment of and protection against NIHL. In the second step, we searched the names of the agents identified in the first step, together with the term "noise induced hearing loss," and reviewed the results. PMID- 26882915 TI - Suicidality and aggression during antidepressant treatment: authors misinterpreted earlier paper from the FDA. PMID- 26882916 TI - Authors' reply to Smith and colleagues. PMID- 26882912 TI - Clinical practice guideline: tonsillitis II. Surgical management. AB - In 2013, a total of 84,332 patients had undergone extracapsular tonsillectomies (TE) and 11,493 a tonsillotomy (TT) procedure in Germany. While the latter is increasingly performed, the number of the former is continually decreasing. However, a constant number of approximately 12,000 surgical procedures in terms of abscess-tonsillectomies or incision and drainage are annually performed in Germany to treat patients with a peritonsillar abscess. The purpose of this part of the clinical guideline is to provide clinicians in any setting with a clinically focused multi-disciplinary guidance through the surgical treatment options to reduce inappropriate variation in clinical care, improve clinical outcome and reduce harm. Surgical treatment options encompass intracapsular as well as extracapsular tonsil surgery and are related to three distinct entities: recurrent episodes of (1) acute tonsillitis, (2) peritonsillar abscess and (3) infectious mononucleosis. Conservative management of these entities is subject of part I of this guideline. (1) The quality of evidence for TE to resolve recurrent episodes of tonsillitis is moderate for children and low for adults. Conclusions concerning the efficacy of TE on the number of sore throat episodes per year are limited to 12 postoperative months in children and 5-6 months in adults. The impact of TE on the number of sore throat episodes per year in children is modest. Due to the heterogeneity of data, no firm conclusions on the effectiveness of TE in adults can be drawn. There is still an urgent need for further research to reliably estimate the value of TE compared to non-surgical therapy of tonsillitis/tonsillo-pharyngitis. The impact of TE on quality of life is considered as being positive, but further research is mandatory to establish appropriate inventories and standardized evaluation procedures, especially in children. In contrast to TE, TT or comparable procedures are characterized by a substantially lower postoperative morbidity in terms of pain and bleeding. Although tonsillar tissue remains along the capsule, the outcome appears not to differ from TE, at least in the pediatric population and young adults. Age and a history of tonsillitis are not a contraindication, abscess formation in the tonsillar remnants is an extremely rare finding. The volume of the tonsils should be graded according to Brodsky and a grade >1 is considered to be eligible for TT. The number of episodes during 12 months prior to presentation is crucial to indicate either TE or TT. While surgery is not indicated in patients with less than three episodes, a wait-and-see policy for 6 months is justified to include the potential of a spontaneous healing before surgery is considered. Six or more episodes appear to justify tonsil surgery. (2) Needle aspiration, incision and drainage, and abscess tonsillectomy are effective methods to treat patients with peritonsillar abscess. Compliance and ability of the patient to cooperate must be taken into account when choosing the surgical method. Simultaneous antibiotic therapy is recommended but still subject of scientific research. Abscess tonsillectomy should be preferred, if complications have occurred or if alternative therapeutic procedures had failed. Simultaneous TE of the contralateral side should only be performed when criteria for elective TE are matched or in cases of bilateral peritonsillar abscess. Needle aspiration or incision and drainage should be preferred if co-morbidities exist or an increased surgical risk or coagulation disorders are present. Recurrences of peritonsillar abscesses after needle aspiration or incision and drainage are rare. Interval TE should not be performed, the approach is not supported by contemporary clinical studies. (3) In patients with infectious mononucleosis TE should not be performed as a routine procedure for symptom control. TE is indicated in cases with clinically significant upper airway obstruction resulting from inflammatory tonsillar hyperplasia. If signs of a concomitant bacterial infection are not present, antibiotics should not be applied. Steroids may be administered for symptom relief. PMID- 26882919 TI - Erratum to: The efficacy of continuous subcostal transversus abdominis plane block for analgesia after living liver donation: a retrospective study. PMID- 26882918 TI - Revisiting cobalt chloride preconditioning to prevent hypobaric hypoxia-induced damage: identification of global proteomic alteration and key networks. AB - Several studies have supported the hypoxia mimetic roles and cytoprotective properties of cobalt chloride in vitro and in vivo. However, a clear understanding of biological process-based mechanism that integrates the available information remains unknown. This study was aimed to explore the potential mechanism of cobalt chloride deciphering its benefits and well-known physiological challenge caused by hypobaric hypoxia that reportedly affects nearly 24 % of the global population. In order to explore the mechanism of CoCl2, we used global proteomic and systems biology approach in rat model to provide a deeper insight into molecular mechanisms of preconditioning. Furthermore, key conclusions were drawn based on biological network analysis and their enrichment with ontological overlaps. The study was further strengthened by consistent identification of validation of proteins using immunoblotting. CoCl2-pretreated animals exposed to hypoxia showed two significant networks, one lipid metabolism and other cell cycle associated, with a total score of 23 and eight focus molecules. In this study, we delineated two primary routes: one, by direct modulation of reactive oxygen species metabolism and, second, by regulation of lipid metabolism which was not known until now. The previously known benefits of cobalt chloride during physiological challenge by hypobaric hypoxia are convincing and could be explained by some basic set of metabolic and molecular reorganization within the hypoxia model. Interestingly, we also observed some of the completely unknown roles of cobalt chloride such as regulation of lipid that could undulate the translational roles of cobalt chloride supplementation beyond hypoxia preconditioning. PMID- 26882917 TI - Comprehensive identification of LMW-GS genes and their protein products in a common wheat variety. AB - Although it is well known that low-molecular-weight glutenin subunits (LMW-GS) from wheat affect bread and noodle processing quality, the function of specific LMW-GS proteins remains unclear. It is important to find the genes that correspond to individual LMW-GS proteins in order to understand the functions of specific proteins. The objective of this study was to link LMW-GS genes and haplotypes characterized using well known Glu-A3, Glu-B3, and Glu-D3 gene specific primers to their protein products in a single wheat variety. A total of 36 LMW-GS genes and pseudogenes were amplified from the Korean cultivar Keumkang. These include 11 Glu-3 gene haplotypes, two from the Glu-A3 locus, two from the Glu-B3 locus, and seven from the Glu-D3 locus. To establish relationships between gene haplotypes and their protein products, a glutenin protein fraction was separated by two-dimensional gel electrophoresis (2-DGE) and 17 protein spots were analyzed by N-terminal amino acid sequencing and tandem mass spectrometry (MS/MS). LMW-GS proteins were identified that corresponded to all Glu-3 gene haplotypes except the pseudogenes. This is the first report of the comprehensive characterization of LMW-GS genes and their corresponding proteins in a single wheat cultivar. Our approach will be useful to understand the contributions of individual LMW-GS to the end-use quality of flour. PMID- 26882920 TI - Propofol reduces liver dysfunction caused by tumor necrosis factor-alpha production in Kupffer cells. AB - PURPOSE: The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-alpha production in activated Kupffer cells. METHODS: Rats received LPS (500 MUg/kg) under UrethaneTM sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or IntralipidTM from 1 h before to 6 h after LPS administration. Some rats were treated with 10 mg/kg gadolinium chloride (GdCl3) to induce Kupffer cell depletion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-alpha mRNA and protein expression, caspase-3 activation and apoptosis were evaluated in hepatocytes. Immunofluorescence staining revealed expression of the pan-macrophage marker CD68 as well as TNF-alpha in Kupffer cells. RESULTS: ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with IntralipidTM treated rats at 6 h after LPS administration, whereas propofol and GdCl3 reduced the LPS-induced increases. LPS simultaneously augmented TNF-alpha expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF alpha expression in Kupffer cells was inhibited by propofol and GdCl3, resulting in a reduction of caspase-3 activity and apoptosis in LPS-treated rat hepatocytes. CONCLUSIONS: Propofol (5 mg/kg/h) attenuated LPS-triggered liver dysfunction via inhibition of TNF-alpha production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo. PMID- 26882921 TI - Impact of anesthetic technique on the stress response elicited by laparoscopic cholecystectomy: a randomized trial. AB - The aim of this randomized, double-blind clinical trial was to elucidate the impact of general anesthesia alone (GA) or supplemented with epidural anesthesia (EpiGA) on surgical stress response during laparoscopic cholecystectomy, using stress hormones, glucose, and C-reactive protein (CRP), as potential markers. Sixty-two patients scheduled to undergo elective laparoscopic cholecystectomy were randomly assigned into two groups to receive either GA or EpiGA. Stress hormones [cortisol (COR), human growth hormone (hGH), prolactine (PRL)], glucose, and CRP were determined 1 day before surgery, intraoperatively, and upon first postoperative day (POD1). Plasma COR, hGH, PRL, and glucose levels were maximized intraoperatively in GA and EpiGA groups and reverted almost to baseline on POD1. Significant between-group differences were detected for COR and glucose either intraoperatively or postoperatively, but this was not the case for hGH. PRL was elevated in GA group only intraoperatively. Although, CRP was minimally affected intraoperatively, a notable augmentation on POD1, comparable in both groups, was recorded. These results indicate that hormonal and metabolic stress response is slightly modulated by the use of epidural block supplemented by general anesthesia, in patients undergoing laparoscopic cholecystectomy cholecystectomy. Nevertheless, inflammatory reaction as assessed by CRP seems to be unaffected by the anesthesia regimen. PMID- 26882922 TI - Comparison of the analgesic effect of intravenous acetaminophen with that of flurbiprofen axetil on post-breast surgery pain: a randomized controlled trial. AB - OBJECTIVE: Acetaminophen is known to be a relatively weak analgesic with fewer side effects than nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to determine whether intravenous (iv) acetaminophen produces comparable analgesic effects to those of flurbiprofen (positive control drug), an intravenously injectable NSAID, after partial mastectomies. The primary outcome assessed was pain intensity during the first 24 h after the operation, and the secondary outcome was the satisfaction rating at discharge. METHODS: After obtaining Institutional Ethics Committee approval, a series of 40 consecutive female patients who were scheduled for partial mastectomies were enrolled. Participants were randomly divided into two groups: an acetaminophen (1000 mg * 3) group (group A) and a flurbiprofen (50 mg * 3) group (group F). Each drug was administered 15 min before the end of surgery, and at 6 and 12 h after the operation. Postoperative pain was evaluated using a 100-mm visual analog scale (VAS) at 3, 6, and 24 h postoperatively. Satisfaction rating was evaluated on a 5 point scale (very good, good, well, bad, and very bad). RESULTS: VAS scores (mm) with movement in groups A and F at 3, 6, and 24 h after the surgery were 22 vs. 28, 14 vs. 24, and 12 vs. 20.5 (median), respectively, with no significant differences between the two groups. Eighteen of 20 patients in group A and 20 of 20 patients in group F expressed a satisfaction rating of greater than good. CONCLUSIONS: Acetaminophen produces an equivalent analgesic effect to flurbiprofen in post-partial mastectomy patients. PMID- 26882923 TI - Adapting a Low-Cost Selective Compliant Articulated Robotic Arm for Spillage Avoidance. AB - Flexible automation systems provide the needed adaptability to serve shorter-term projects and specialty applications in biochemical analysis. A low-cost selective compliant articulated robotic arm designed for liquid spillage avoidance is developed here. In the vertical-plane robotic arm movement test, the signals from an inertial measurement unit (IMU) and accelerometer were able to sense collisions. In the horizontal movement test, however, only the signals from the IMU enabled collision to be detected. Using a calculation method developed, it was possible to chart the regions where the obstacle was likely to be located when a collision occurred. The low cost of the IMU and its easy incorporation into the robotic arm offer the potential to meet the pressures of lowering operating costs, apply laboratory automation in resource-limited venues, and obviate human intervention in response to sudden disease outbreaks. PMID- 26882924 TI - Intracellular Delivery by Shape Anisotropic Magnetic Particle-Induced Cell Membrane Cuts. AB - Introducing functional macromolecules into a variety of living cells is challenging but important for biology research and cell-based therapies. We report a novel cell delivery platform based on rotating shape anisotropic magnetic particles (SAMPs), which make very small cuts on cell membranes for macromolecule delivery with high efficiency and high survivability. SAMP delivery is performed by placing commercially available nickel powder onto cells grown in standard cell culture dishes. Application of a uniform magnetic field causes the magnetic particles to rotate because of mechanical torques induced by shape anisotropic magnetization. Cells touching these rotating particles are nicked, which generates transient membrane pores that enable the delivery of macromolecules into the cytosol of cells. Calcein dye, 3 and 40 kDa dextran polymers, a green fluorescence protein (GFP) plasmid, siRNA, and an enzyme (beta lactamase) were successfully delivered into HeLa cells, primary normal human dermal fibroblasts (NHDFs), and mouse cortical neurons that can be difficult to transfect. The SAMP approach offers several advantages, including easy implementation, low cost, high throughput, and efficient delivery of a broad range of macromolecules. Collectively, SAMP delivery has great potential for a broad range of academic and industrial applications. PMID- 26882925 TI - Lowering Heart Rate Post Revascularization: Angina and Quality of Life Improvement. PMID- 26882926 TI - Retrograde Percutaneous Coronary Intervention for Chronic Total Occlusion: Sine Qua Non of Success. PMID- 26882927 TI - Examination of overall treatment effect and the proportion attributable to contextual effect in osteoarthritis: meta-analysis of randomised controlled trials. AB - OBJECTIVE: To examine the overall treatment effect and the proportion attributable to contextual effect (PCE) in randomised controlled trials (RCTs) of diverse treatments for osteoarthritis (OA). METHODS: We searched Medline, Embase, Central, Science Citation Index, AMED and CINAHL through October 2014, supplemented with manual search of reference lists, published meta-analyses and systematic reviews. Included were RCTs in OA comparing placebo with representative complementary, pharmacological, non-pharmacological and surgical treatments. The primary outcome was pain. Secondary outcomes were function and stiffness. The effect size (ES) of overall treatment effect and the PCE were pooled using random-effects model. Subgroup analyses and meta-regression were conducted to examine determinants of the PCE. RESULTS: In total, 215 trials (41 392 participants) were included. The overall treatment effect for pain ranged from the smallest with lavage (ES=0.46, 95% CI 0.24 to 0.68) to the largest with topical non-steroidal anti-inflammatory drugs (ES=1.37, 95% CI 1.19 to 1.55). On average, 75% (PCE=0.75, 95% CI 0.72 to 0.79) of pain reduction was attributable to contextual effect. It varied by treatment from 47% (PCE=0.47, 95% CI 0.32 to 0.70) for intra-articular corticosteroid to 91% (PCE=0.91, 95% CI 0.60 to 1.37) for joint lavage. Similar results were observed for function and stiffness. Treatment delivered by needle/injection and other means than oral medication, longer duration of treatment, large sample size (>=100 per arm) and public funding source were associated with increased PCE for pain reduction. CONCLUSIONS: The majority (75%) of the overall treatment effect in OA RCTs is attributable to contextual effects rather than the specific effect of treatments. Reporting overall treatment effect and PCE, in addition to traditional ES, permits a more balanced, clinically meaningful interpretation of RCT results. This would help dispel the frequent discordance between conclusions from RCT evidence and clinical experience-the 'efficacy paradox'. PMID- 26882929 TI - Induced gene expression in industrial Saccharomyces pastorianus var. carlsbergensis TUM 34/70: evaluation of temperature and ethanol inducible native promoters. AB - Induced gene expression is an important trait in yeast metabolic engineering, but current regulations prevent the use of conventional expression systems, such as galactose and copper, in food and beverage fermentations. This article examines the suitability of temperature-inducible native promoters for use in the industrial yeast strain Saccharomyces pastorianus var. carlsbergensis TUM 34/70 under brewing conditions. Ten different promoters were cloned and characterized under varying temperature shifts and ethanol concentrations using a green fluorescent protein reporter. The activities of these promoters varied depending upon the stress conditions applied. A temperature shift to 4 degrees C led to the highest fold changes of PSSA3, PUBI4 and PHSP104 by 5.4, 4.5 and 5.0, respectively. Ethanol shock at 24 degrees C showed marked, concentration dependent induction of the promoters. Here, PHSP104 showed its highest induction at ethanol concentrations between 4% (v/v) and 6% (v/v). The highest fold changes of PSSA3 and PUBI4 were found at 10% (v/v) ethanol. In comparison, the ethanol shock at a typical fermentation temperature (12 degrees C) leads to lower induction patterns of these promoters. Taken together, the data show that three promoters (PHSP104, PUBI4 and PSSA3) have high potential for targeted gene expression in self-cloning brewing yeast using temperature shifts. PMID- 26882928 TI - Does flare trial design affect the effect size of non-steroidal anti-inflammatory drugs in symptomatic osteoarthritis? A systematic review and meta-analysis. AB - OBJECTIVES: It is thought that the clinical trial benefits of oral non-steroidal anti-inflammatory drugs (NSAIDs) may relate to flare designs. The aim of this study was to examine the difference in NSAID (including cyclooxygenase-2 (COX-2) inhibitors) response in osteoarthritis (OA) trials based on different designs. METHODS: Systematic review was undertaken of the databases MEDLINE, EMBASE, AMED, CINAHL and the Cochrane library till February 2015. Randomised controlled trials assessing pain, function and/or stiffness following commencement of NSAIDs in flare and non-flare designs were eligible. Trials were assessed using the Cochrane Risk of Bias tool. Meta-analyses were conducted to assess the effect sizes (ES) of NSAIDs for OA with flare versus non-flare trial designs. RESULTS: Fifty-seven studies including 33 263 participants assessing 26 NSAIDs were included. Twenty-two (39%) were flare design, 24 (42%) were non-flare designs, 11 (19%) were possible flare designs. On meta-analysis, there was no statistically significant difference in ES of NSAIDs versus placebo between flare and non-flare trial designs for absolute pain and function or stiffness at immediate-term (1 week), short-term (2-4 week) or longer-term (12-13 week) follow-up periods (p>0.05). However there was a lower ES for mean change in pain in flare and possible flare trials compared with non-flare trials at short-term follow-up (0.36 vs 0.69; p=0.05). CONCLUSIONS: Contrary to previous understanding, flare trial designs do not result in an increased treatment effect for NSAIDs in people with OA compared with non-flare design. Whether flare design influences other outcomes such as joint effusion remains unknown. PMID- 26882931 TI - Image of the Month: Lymphocytic Esophagitis in Common Variable Immune Deficiency. PMID- 26882930 TI - Comparative study of Saccharomyces cerevisiae wine strains to identify potential marker genes correlated to desiccation stress tolerance. AB - The most diffused formulation of starter for winemaking is active dry yeast (ADY). ADYs production process is essentially characterized by air-drying stress, a combination of several stresses, including thermal, hyperosmotic and oxidative and cell capacity to counteract such multiple stresses will determine its survival. The molecular mechanisms underlying cell stress response to desiccation have been mostly studied in laboratory and commercial yeast strains, but a growing interest is currently developing for indigenous yeast strains which represent a valuable and alternative source of genetic and molecular biodiversity to be exploited. In this work, a comparative study of different Saccharomyces cerevisiae indigenous wine strains, previously selected for their technological traits, has been carried out to identify potentially relevant genes involved in desiccation stress tolerance. Cell viability was evaluated along desiccation treatment and gene expression was analyzed by real-time PCR before and during the stress. Our data show that the observed differences in individual strain sensitivity to desiccation stress could be associated to specific gene expression over time. In particular, either the basal or the stress-induced mRNA levels of certain genes, such as HSP12, SSA3, TPS1, TPS2, CTT1 and SOD1, result tightly correlated to the strain survival advantage. This study provides a reliable and sensitive method to predict desiccation stress tolerance of indigenous wine yeast strains which could be preliminary to biotechnological applications. PMID- 26882932 TI - Images of the Month: Happy Valentine's Day. PMID- 26882934 TI - Images of the Month: A Rare Cause of Overt Gastrointestinal Bleeding. PMID- 26882933 TI - Images of the Month: Hepatic Reactive Amyloidosis Secondary to Chronic Osteomyelitis. PMID- 26882935 TI - Image of the Month: A Small Bowel With Too Many Exits: An Astonishing Surgical Finding in a Patient With Crohn's Disease. PMID- 26882936 TI - Image of the Month: Viable Hepatocellular Carcinoma Foci in Radiological Complete Remission After Transarterial Embolization. PMID- 26882937 TI - Images of the Month: Visible Peristalsis. PMID- 26882938 TI - Images of the Month: Schistosomiasis as a Solitary Sigmoid Nodule. PMID- 26882939 TI - Video of the Month: The Colonic Tug of War: Removal of a Retained Surgical Item. PMID- 26882944 TI - Eosinophilic Esophagitis Dilation in the Community--Try It--You will Like It--But Start Low and Go Slow. AB - The saga of esophageal dilation for patients with eosinophilic esophagitis and strictures reads like a historical novel. Currently, data from over 500 eosinophilic esophagitis (EoE) patients now convincingly prove that esophageal dilation is effective for prolonged relief and safe. It can easily be performed in the gastroenterologists community but follow the basic tenets of starting low with small diameter bougies/balloons and progressing slowly as you gradually dilate these strictures to 16-18 mm. Table 1 outlines my approach. PMID- 26882945 TI - Low-Dose Tricyclics for Esophageal Hypersensitivity: Is it all Placebo Effect? AB - Limsrivilai et al. report on a randomized control trial (RCT) testing the efficacy of imipramine for treating esophageal hypersensitivity and functional heartburn, the first RCT to test this therapy in this indication. Among 43 functional heartburn and esophageal hypersensitivity patients randomized to treatment with 25 mg qhs imipramine and 40 randomized to matched placebo, the response rates, judged by a 50% reduction in gastroesophageal reflux disease symptoms, were 37.2% and 37.5%, respectively, with no observed difference between patients with hypersensitivity and those with functional heartburn. On the positive side, imipramine treatment was associated with improvement in quality of life as assessed by total SF-36 score. Although negative at first glance, there are several important lessons from this study: (i) low-dose tricyclic is sufficient in these patients; (ii) proton pump inhibitors can (and should) be discontinued when they are ineffective; and (iii) distinguishing between functional heartburn and esophageal hypersensitivity is of unclear clinical relevance. PMID- 26882946 TI - Response to Perez-Cuadrado Robles. PMID- 26882947 TI - Emergency Capsule Endoscopy and Balloon-Assisted Enteroscopy may be a First-Line Procedure in Massive Acute Overt-Obscure Gastrointestinal Bleeding. PMID- 26882949 TI - Response to Farre. PMID- 26882948 TI - Evaluating the Esophageal Epithelial Integrity: More Complex than it Seems. PMID- 26882950 TI - Response to Collyer et al. PMID- 26882951 TI - Response to Fontana et al. PMID- 26882953 TI - BCL-3 promotes the tumor growth of hepatocellular carcinoma by regulating cell proliferation and the cell cycle through cyclin D1. AB - Previous studies have demonstrated the aberrant expression and oncogenic role of B-cell CLL/lymphoma-3 (BCL-3) in human malignancies. However, the clinical significance of BCL-3 and its biological function in human hepatocellular carcinoma (HCC) remain unknown. In the present study, the expression levels of BCL-3 protein and mRNA in 90 pairs of HCC and matched non-tumor tissues were analyzed using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We found that the expression levels of BCL-3 protein and mRNA in HCC tissues were significantly higher than those in the matched tumor-adjacent tissues. In addition, positive expression of BCL-3 was associated with adverse clinicopathological characteristics of the HCC patients including hepatitis B virus (HBV) infection, tumor size, cirrhosis and advanced tumor-node-metastasis (TNM) stage. Moreover, HCC patients with positive expression of BCL-3 had significantly decreased 5-year overall survival and recurrence-free survival. Importantly, BCL-3 expression was an independent prognostic factor for indicating the survival of the HCC patients. Functionally, BCL-3 knockdown markedly inhibited cell viability, proliferation and cell cycle progression in HepG2 cells, while BCL-3 overexpression promoted these cellular processes in Huh7 cells. Accordingly, in vivo experiments indicated that BCL-3 knockdown prominently suppressed the tumor growth of HepG2 cells in nude mice. Mechanistically, we revealed that the expression of cyclin D1 was decreased after BCL-3 knockdown in the HepG2 cells and was increased after BCL-3 overexpression in the Huh7 cells. Cyclin D1 silencing was found to abrogate the functional effects of BCL-3 on cellular processes in Huh7 cells. Taken together, our data suggest that BCL-3 may serve as a promising biomarker and an effective therapeutic target of HCC. PMID- 26882955 TI - Immunotherapy for small-cell lung cancer: emerging evidence. AB - Treatment for small-cell lung cancer (SCLC) has changed little over the past few decades; available therapies have failed to extend survival in advanced disease. In recent years, immunotherapy with treatments such as interferons, TNFs, vaccines and immune checkpoint inhibitors has advanced and shown promise in the treatment of several tumor types. Immune checkpoint inhibitors such as ipilimumab, nivolumab, pembrolizumab, durvalumab, tremelimumab and ulocuplumab are at the forefront of immunotherapy and have achieved approvals for certain cancer types, including melanoma (ipilimumab, nivolumab and pembrolizumab), non SCLC (nivolumab and pembrolizumab) and renal cell carcinoma (nivolumab). Clinical trials are investigating different immunotherapies in patients with other solid and hematologic malignancies, including SCLC. We review emerging evidence supporting the use of immunotherapy in SCLC patients. PMID- 26882954 TI - Electrochemical sensing of etoposide using carbon quantum dot modified glassy carbon electrode. AB - In this study, enhancement of the electrochemical signals of etoposide (ETO) measured by differential pulse voltammetry (DPV) by modifying a glassy carbon electrode (GCE) with carbon quantum dots (CQDs) is demonstrated. In comparison with a bare GCE, the modified GCE exhibited a higher sensitivity towards electrochemical detection of ETO. The lowest limit of detection was observed to be 5 nM ETO. Furthermore, scanning electron microscopy (SEM), fluorescence microscopy (FM), and electrochemical impedance spectroscopy (EIS) were employed for the further study of the working electrode surface after the modification with CQDs. Finally, the GCE modified with CQDs under optimized conditions was used to analyse real samples of ETO in the prostate cancer cell line PC3. After different incubation times (1, 3, 6, 9, 12, 18 and 24 h), these samples were then prepared prior to electrochemical detection by the GCE modified with CQDs. High performance liquid chromatography with an electrochemical detection method was employed to verify the results from the GCE modified with CQDs. PMID- 26882956 TI - Musculoskeletal Proportionality, Biomechanical Considerations, and Their Contribution to Movement in Adults and Children. AB - The musculoskeletal system grows greatly throughout maturation. When trying to explain differences in strength, power and movement patterns between adults and children many pediatric exercise scientists will assume that this growth is proportional in all dimensions and structures. This article examines the evidence underpinning these assumptions, and considers how changes in fascicle, muscle, tendon and joint proportions may contribute to maturation-induced changes in physical performance. There are only a small number of studies to draw upon, but they consistently indicate that 1) growth changes the functional design of muscles, so that they become better at producing large forces at slow speeds but less able to achieve large length changes or high velocities; 2) the skeleton appears to grow somewhat proportionally before puberty, but this changes throughout adolescence, meaning the moment arm about which the muscle acts does not remain proportional to muscle length or the external moment arm about which joint work acts on the external world. In combination these results show that external measures of whole body or joint performance do not reflect the actual internal muscle function similarly in children and adults. Since our purpose should be to explain and not just describe maturation-induced changes in performance, greater efforts are needed to understand the internal "engine" driving our movement. This necessitates more detailed, longitudinal and dynamically loaded studies of the structure and function of the muscles and their interaction with the skeleton throughout maturation. PMID- 26882957 TI - Solution-processed carrier selective layers for high efficiency organic/nanostructured-silicon hybrid solar cells. AB - The reduction of interface minority carrier recombination is regarded as a key performance indicator in improving the power conversion efficiency (PCE) of organic-inorganic hybrid solar cells. In this study, we chose two kinds of carrier-selective layers to be applied in a hybrid solar cell device. A hole selective transporting layer of N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD) was added to the interface between Si nanohole structures and PEDOT: PSS, and the electron selective layer cesium carbonate (Cs2CO3) was added to the interface between the backside Si wafer and the rear Ti/Ag electrode. The main process used a clean and low-cost solution process, and the annealed temperature was under 140 degrees C. In addition, after we inserted these two carrier selective layers, the minority carrier lifetime was prolonged from 29.98 MUs to 140.81 MUs, indicating its significance in reducing the recombination rate. Eventually, we demonstrated that the PCE of Si/organic heterojunction solar cells can be improved to 13.23%. PMID- 26882958 TI - Stroke patients' and informal carers' experiences with life after stroke: an overview of qualitative systematic reviews. AB - Purpose To provide a systematic overview of current qualitative systematic reviews and metasyntheses of patients' and informal carers' experiences with rehabilitation and life after stroke following discharge. Method A systematic literature search was performed based on PRISMA guidelines. Nine databases were systematically searched by a university librarian. The search yielded 1093 unique entries and screening by title/abstract identified 60 reviews for potential inclusion. After full-text assessment by two independent observers, 11 reviews satisfied the inclusion criteria. Following quality appraisal, four studies were excluded. Results Seven qualitative reviews (containing 108 primary studies) were included: five reviews of patients' experiences and two reviews of carers' experiences. Stroke causes profound disruption of life as known, and both patients and carers must engage in a process of adapting and rebuilding a post stroke life and identity. This process of rehabilitation is described as temperamental and unstable rather than progressive. From the reviews, five key experiences in this process are identified: autonomy, uncertainty, engagement, hope and social relations. Conclusions The need for broad, qualitative syntheses of stroke patients' experiences is currently fulfilled. Future qualitative reviews could focus more on implications for practice, e.g., by grading the quality of the metafindings. Implications for Rehabilitation Stroke is a profound disruption of life as known, and patients and carers value information that helps them prepare for and adjust to this new situation. Optimal rehabilitation is a main concern and goal for patients and carers, and thus carers may be a valuable asset to professionals in the rehabilitation process. Practical and emotional support is important for patients and carers, and rehabilitation professionals should be aware of the increased risk of social isolation post-stroke. Hope is a strong motivational factor and coping strategy for patients and carers. However, as hope may wane in the case of continued residual impairment, rehabilitation professionals should prepare patients and carers for this situation. PMID- 26882959 TI - Outcomes of Bleomycin-based electrochemotherapy in patients with repeated loco regional recurrences of vulvar cancer. AB - Objective To evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments. Methods Ten patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires. Results Diagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD +/- 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10-20) min. After a median follow-up of 12 (3-22) months, six patients (60%) were alive. Conclusions Objective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3-22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting. PMID- 26882960 TI - Dual-phase CT for the assessment of acute vascular injuries in high-energy blunt trauma: the imaging findings and management implications. AB - Acute vascular injuries are the second most common cause of fatalities in patients with multiple traumatic injuries; thus, prompt identification and management is essential for patient survival. Over the past few years, multidetector CT (MDCT) using dual-phase scanning protocol has become the imaging modality of choice in high-energy deceleration traumas. The objective of this article was to review the role of dual-phase MDCT in the identification and management of acute vascular injuries, particularly in the chest and abdomen following multiple traumatic injuries. In addition, this article will provide examples of MDCT features of acute vascular injuries with correlative surgical and interventional findings. PMID- 26882961 TI - Assistive technologies for hearing, and speaking impaired people: a survey. AB - This study presents a novel method for evaluating the scientific research papers in the field of assistive technologies pertaining to different impairment conditions. The objectives are to understand the technologies used for addressing the needs of PWD by identifying relevant criteria for the assessment, explore the implications of these technologies in their lives and identify the gaps among certain technologies in assisting PWD. In this article, we reviewed around 40 research scientific papers in relation to the technologies used to assist PWD in their daily activities. A novel quantitative assessment methodology based on Multi-weighted Scoring Model (MWSM) has been developed. It is based on the judgement of clinical experts according to thirteen well-defined criteria. The proposed method is useful because it assesses the scientific studies related to PWD qualitatively according to efficient research coverage, as well as quantitatively in order to have good comparative judgment. Moreover, this method recognizes the research gap or areas which need further investigation and identifies the research papers that have good coverage of the respective criteria. Implications for Rehabilitation Human computer interface (HCI) solutions are critical for addressing the main issues facing people with disabilities (PWD) in their life. Assessment of scientific research papers according to well-defined criteria that address PWD needs would assist in verifying their suitability for PWDs. Novel quantitative assessment methodology is used for assessing these research papers using judgment of experienced researchers according to 13 well-defined criteria that have been weighted according to relevancy to different impairment groups. Identifying research papers that have good coverage of defined criteria and knowing the research area that needs further investigation by researchers and developers, would ultimately address the rehabilitation needs for PWD. PMID- 26882962 TI - Plant polyphenols alter a pathway of energy metabolism by inhibiting fecal Bacteroidetes and Firmicutes in vitro. AB - The function of plant polyphenols in controlling body weight has been in focus for a long time. The aim of this study was to investigate the effect of plant polyphenols on fecal microbiota utilizing oligosaccharides. Three plant polyphenols, quercetin, catechin and puerarin, were added into liquid media for fermenting for 24 h. The pH values, OD600 of the cultures and the content of carbohydrates at 0, 6, 10, 14, 18 and 24 h were determined. The abundance of Bacteroidetes and Firmicutes in each culture was quantified with qPCR after 10 h of fermentation, and the bacterial composition was analyzed using the software Quantitative Insights Into Microbial Ecology. The results revealed that all three plant polyphenols could significantly inhibit the growth of Bacteroidetes (P < 0.01) and Firmicutes (P < 0.01) while at the same time down-regulate the ratio of Bacteroidetes to Firmicutes (P < 0.01). But the fecal bacteria could maintain the ability to hydrolyze fructo-oligosaccharide (FOS) in vitro. Among the tested polyphenols, catechin presented the most intense inhibitory activity towards the growth of Bacteroidetes and Firmicutes, and quercetin was the second. Only the samples with catechin had a significantly lower energy metabolism (P < 0.05). In conclusion, plant polyphenols can change the pathway of degrading FOS or even energy metabolism in vivo by altering gut microbiota composition. It may be one of the mechanisms in which plant polyphenols can lead to body weight loss. It's the first report to study in vitro gastrointestinal microbiota fermenting dietary fibers under the intervention of plant polyphenols. PMID- 26882964 TI - Cooperative effects of different temperatures and pressures on the initial and subsequent decomposition reactions of the nitrogen-rich energetic crystal 3,3' dinitroamino-4,4'-azoxyfurazan. AB - We performed ab initio molecular dynamics simulations to study the initiation mechanisms and subsequent chemical decomposition reactions of the nitrogen-rich furazan explosive 3,3'-dinitroamino-4,4'-azoxyfurazan (DNAAF) at low temperatures (363-963 K) coupled with different pressures (1-5 GPa). Two different initial decomposition mechanisms which are dependent on the temperature and pressure were found: bimolecular intermolecular hydrogen transfer and unimolecular N-NO2 bond breaking. The subsequent decomposition reactions are sensitive to both the temperature and the pressure. The pressure could accelerate or decelerate the decomposition of DNAAF, while the temperature can change the effect of the pressure on the decomposition. Our study may provide new insights into the initial mechanisms and subsequent decomposition of furazan explosives at low temperatures coupled with different pressures in atomic detail. PMID- 26882965 TI - Practical Considerations for Accepting "Self-Referred" Patients for Radiologic Screenings. PMID- 26882966 TI - Medial Patellofemoral Ligament Reconstruction With Concomitant Tibial Tubercle Transfer: A Systematic Review of Outcomes and Complications. AB - PURPOSE: To examine the outcomes and complications of medial patellofemoral ligament (MPFL) reconstruction and concomitant tibial tubercle (TT) transfer. METHODS: A systematic review of published literature on MPFL reconstruction and TT transfer was performed using the following databases: PubMed/Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), SPORTDiscus, and Cochrane. To be included, studies were required to present outcomes and/or complication data for MPFL reconstruction performed in combination with TT transfer. Each study was assessed for quality and level of evidence. RESULTS: Five studies consisting of 92 knees met the inclusion criteria. Between 57% and 77% of the patients were female patients, and the mean age at surgery was 20.6 years (range, 19 to 31 years). The mean follow-up period was 38 months (range, 23 to 53 months). Postoperative outcome measures including the Lysholm score, Kujala score, International Knee Documentation Committee score, Knee Injury and Osteoarthritis Outcome Score, and visual analog scale score were similar to those previously reported for isolated MPFL reconstruction. Reported complication rates were lower than 15% and included wound infection, hardware irritation, and stiffness. Four studies were graded as Level IV evidence, and 1 study was graded as Level II evidence. Only 1 study scored greater than 50% in the quality analysis. CONCLUSIONS: Results from the analyzed studies indicate that MPFL reconstruction combined with TT transfer is a safe and effective procedure, with a low to moderate risk of complications but overall favorable results. TT transfer is most often performed in conjunction with MPFL reconstruction in the setting of malalignment such as an increased TT-to-trochlear groove distance, and although the surgical indications may differ, the outcomes and risk profiles are similar to those of isolated MPFL reconstruction. With the recognition that these patients are difficult to standardize, additional well-designed studies are needed to further investigate the ideal surgical candidates for MPFL reconstruction with concomitant TT transfer. LEVEL OF EVIDENCE: Level IV, systematic review of Level II and IV studies. PMID- 26882967 TI - Predictors of the Clinical Outcome After Arthroscopic Partial Meniscectomy for Acute Trauma-Related Symptomatic Medial Meniscal Tear in Patients More Than 60 Years of Age. AB - PURPOSE: To determine predictors of the clinical outcome after arthroscopic partial meniscectomy performed for acute trauma-related medial meniscal tear leading to mechanical symptoms in patients more than 60 years of age. METHODS: In this retrospective study with 4.1 years' follow-up, the clinical data of 154 arthroscopic partial medial meniscectomies were evaluated. The body mass index (BMI), duration of symptoms, the hip-knee-ankle angle, type of the meniscal tear, presence of any chondral lesions, degenerative changes in the patellofemoral joint, the status of the cruciate ligaments and lateral meniscus, and the presence of any plica or synovitis were the independent variables. Visual Analog Scale (VAS) and Lysholm Knee Scoring Scale were the instruments used as outcome measures. Multivariate analysis was performed to determine the major predictors. RESULTS: The mean VAS score for 154 knees evaluated in this study improved from 5.6 points preoperatively to 2.3 points at the latest follow-up. The mean Lysholm score improved from 43 points to 72.7 points. VAS and Lysholm scores at the latest follow-up were significantly worse in patients with a preoperative BMI >= 26 kg/m(2), hip-knee-ankle angle > 5 degrees , grade III or IV chondral lesion of the medial compartment according to Outerbridge classification, degenerative changes in patellofemoral joint surfaces, and an anterior cruciate ligament that was either partially ruptured or degenerative with increased laxity. CONCLUSIONS: A preoperative BMI >= 26 kg/m(2), Outerbridge grade III or IV chondral lesion of the medial compartment of the operated knee joint diagnosed during arthroscopic intervention, degenerative changes in patellofemoral joint surfaces, and the presence of an anterior cruciate ligament either partially ruptured or degenerative with increased laxity should be considered as the major predictors of the clinical outcome after arthroscopic partial meniscectomy performed for acute trauma-related symptomatic medial meniscal tear in patients more than 60 years of age. LEVEL OF EVIDENCE: Level IV, prognostic case series. PMID- 26882968 TI - A Preliminary Experience with Use of Intraoperative Magnetic Resonance Imaging in Thalamic Glioma Surgery: A Case Series of 38 Patients. AB - BACKGROUND: Thalamic gliomas are rare tumors that constitute 1%-5% of all central nervous system tumors. Despite advanced techniques and equipment, surgical resection remains challenging because of the vital structures adjacent to the tumor. Intraoperative magnetic resonance imaging (MRI) might play an active role during brain tumor surgery because it compensates for brain shift or operation induced hemorrhage, which are challenging issues for neurosurgeons. METHODS: We reviewed 38 patients treated surgically under intraoperative MRI guidance between January 2008 and July 2015 at our center. Preoperative, intraoperative, and postoperative MRI scans were reviewed. Preoperative and postoperative motor power, morbidity and mortality, resection rate, surgical approach, pathologic results, and patient demographics were also reviewed. RESULTS: Mean patient age was 37 years +/- 18; 12 patients were included in the low-grade group, and 26 patients were included in the high-grade group. Under intraoperative MRI guidance, the gross total resection rate was increased from 16 (42.1%) to 26 (68.4%), and the near-total or subtotal resection rate was increased from 5 (13.2%) to 9 (23.7%). Hematoma formation was discovered in 3 patients on intraoperative MRI scan; each patient underwent a hemostatic operation immediately. CONCLUSIONS: With improvements in neurosurgical techniques and equipment, surgical resection is considered feasible in patients with thalamic gliomas. Intraoperative MRI may be helpful in achieving the maximal resection rate with minimal surgical-related morbidity. However, because of severe disease progression, the overall prognosis is unfavorable. PMID- 26882969 TI - Hydrocephalus Caused by Fat Embolism: A Rare Complication of Atlanto-Axial Fixation for Odontoid Fractures. AB - BACKGROUND AND IMPORTANCE: Odontoid fracture is not uncommon and surgical treatment that uses posterior screw/rod fixation is an acceptable option. This is the first report of delayed hydrocephalus due to subarachnoid fat migration as a complication of posterior atlanto-axial (AA) fixation. CASE DESCRIPTION: A 27 year-old man underwent posterior C1 lateral mass and C2 pedicle screw fixation for a recent Anderson-D'Alonzo type 2 odontoid fracture. Autologous bone graft was wired for onlay fusion. The surgery was smooth, except that there was an incidental durotomy intraoperatively. The patient had significant relief of his neck pain, although computed tomography (CT) demonstrated a medial breach of the left C1 screw postoperation; however, he gradually developed headache and dizziness after discharge. Five weeks after operation, magnetic resonance imaging demonstrated a large pseudo-meningocele at the surgical site, which was managed conservatively. Nine weeks after the AA fixation, the patient was sent to the emergency department for altered consciousness. A brain CT demonstrated hydrocephalus and multiple fat emboli in the subarachnoid and intraventricular space. A ventriculoperitoneal shunt was inserted to manage the hydrocephalus and pseudo-meningocele. The patient recovered well and was followed up to 13 months after operation. To date, this was the first report of delayed hydrocephalus caused by fat embolism after AA fixation surgery. CONCLUSIONS: Incidental durotomy in posterior AA fixation may predispose the patient to a serious complication of fat-cerebrospinal fluid embolism and subsequent hydrocephalus. There should be a heightened awareness for such a complication. Both CT and magnetic resonance imaging are useful for the diagnosis of subarachnoid fat droplets. PMID- 26882970 TI - Outcome after Surgical Treatment for Late Recurrent Lumbar Disc Herniations in Standard Open Microsurgery. AB - PURPOSE: There is a lack of studies highlighting the outcome by different scores or parameters after surgery for recurrent disc herniations of the lumbar spine at the initial herniation site. This study assessed the quality of life after surgical treatment of recurrent herniations with different standardized validated outcome instruments. METHODS: During a 24-month period, 64 patients underwent (microscope assisted) surgery for recurrent disc herniations of the lumbar spine. The postoperative quality of life was tested with Short Form-36, the Oswestry Disability Index, the EuroQol health status 5D, and Prolo questionnaires. Leg and back pain before and after surgery was assessed. RESULTS: The patients showed a good overall outcome, but still not satisfying enough compared with the very good surgical results reported in the literature, for the surgical treatment of primary disc herniations. CONCLUSIONS: Patients have to be informed carefully before surgery of recurrent lumbar disc herniations because of the less-promising outcome than after first time surgery for a lumbar disc herniation. PMID- 26882971 TI - Central Nervous System Melioidosis Mimics Malignancy: A Case Report and Literature Review. AB - BACKGROUND: Central nervous system (CNS) melioidosis is notorious because of the difficulty in bacteria eradication and the destruction of brain structures. Early manifestation of CNS melioidosis mimics malignancy or stroke. We present a case of CNS melioidosis that initially manifested as malignancy. CASE DESCRIPTION: A 30-year-old man presented with sudden onset of left limb weakness and seizure. Computed tomography of the brain showed a low-density lesion over the right parietal lobe, and magnetic resonance imaging showed a well-enhanced lobulated lesion. Neuronavigation-guided open surgery was performed but failed to find a malignancy. The patient presented 3 days later with sudden loss of consciousness, pupil dilation, and high fever. Emergent craniectomy was performed for severe right hemisphere swelling with midline shift. After craniectomy, pus was found in the previous operative field. Burkholderia pseudomallei was cultured from pus and blood samples 1 week after collection. The brain lesion developed into an organized abscess and led to mass effect and ventriculitis. Extraventricular drainage and debridement was performed repeatedly accompanied by systemic and intraventricular antibiotic administration. After 4 months of treatment, the patient achieved a complete consciousness recover while left hemiparesis. CONCLUSIONS: CNS melioidosis requires accurate pathogen identification and appropriate long-term antibiotic treatment for eradication of bacteria and prevention of relapse. Debridement and adequate drainage provide better infection control and outcome. PMID- 26882972 TI - Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells. AB - Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(alpha-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells. PMID- 26882973 TI - High-resolution PTP1B inhibition profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy: Proof-of-concept and antidiabetic constituents in crude extract of Eremophila lucida. AB - Type 2 diabetes (T2D) constituted 90% of the global 387 million diabetes cases in 2014. The enzyme protein-tyrosine phosphatase 1B (PTP1B) has been recognized as a therapeutic target for treatment of T2D and its adverse complications. With the aim of accelerating the investigation of complex natural sources, such as crude plant extracts, for potential PTP1B inhibitors, we have developed a bio analytical platform combining high-resolution PTP1B inhibition profiling and high performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy, i.e., HR-bioassay/HPLC-HRMS SPE-NMR. Human recombinant PTP1B enzyme was used for the microplate-based PTP1B inhibition assay, which was optimized for pH and substrate concentration to be compatible with rate measurements within the 10 min incubation time. Subsequently, analytical-scale HPLC-based microfractionation followed by colorimetric microplate-based PTP1B bioassaying enabled construction of a high resolution inhibition profile corresponding to the HPLC profile. The high resolution PTP1B inhibition profiling was validated using an artificial mixture of known PTP1B inhibitors and non-inhibiting compounds as negative controls. Finally, a proof-of-concept study with a real sample was performed using crude ethyl acetate extract of the phytochemically hitherto unexplored plant Eremophila lucida. This led to the identification of the first viscidane type diterpene, i.e., 5-hydroxyviscida-3,14-dien-20-oic acid (9) as PTP1B inhibitor with an IC50 value of 42.0 +/- 5.9 MUM. In addition, a series of flavonoids, i.e., luteolin (1), dinatin (3a), tricin (3b), 3,6-dimethoxyapigenin (4), jaceidin (5), and cirsimaritin (6) as well as a cembrene diterpene, (3Z, 7E, 11Z)-15-hydroxycembra 3,7,11-trien-19-oic acid (8), were also identified for the first time from E. lucida. PMID- 26882974 TI - FBXO7 mutations in Parkinson's disease and multiple system atrophy. AB - Mutations in the F-box only protein 7 (FBXO7) gene, located on chromosome 22q12 q13, have recently been identified as having distinct clinical features in patients with hereditary Parkinson's disease (PD). Pathologically, alpha synuclein-positive inclusions have been identified using anti-FBXO7 antibody staining techniques. In the present study, we screened entire exons of FBXO7 from 271 patients (231 PD and 40 multiple system atrophy [MSA]), of which 221 samples were of Japanese origin. The PD patients (n = 231) comprised 31 autosomal dominant, 82 autosomal recessive, and 118 sporadic forms. The 40 cases of MSA consisted of 8 autosomal dominant, 2 autosomal recessive, and 30 sporadic forms. We detected a Turkish patient with autosomal recessive inheritance, harboring a homozygous truncating mutation, Arg498Stop (p.R498X), in the FBXO7 gene. Consequently, we evaluated her and assessed the correlation between her clinical manifestations and genotypic analysis, although the FBXO7 p.R498X gene has lower frequency than others. Her age at onset was 17 years, and she clinically manifested with progressive parkinsonism and cognitive decline. In contrast, no pathogenic mutations in FBXO7 among PD and MSA patients of Japanese or other ethnicities were observed. Based on recent literature, we reviewed and compared the clinical findings and population differences between documented FBXO7 cases. PMID- 26882975 TI - Maintaining ocular safety with light exposure, focusing on devices for optogenetic stimulation. AB - Optogenetics methods are rapidly being developed as therapeutic tools for treating neurological diseases, in particular, retinal degenerative diseases. A critical component of the development is testing the safety of the light stimulation used to activate the optogenetic proteins. While the stimulation needs to be sufficient to produce neural responses in the targeted retinal cell class, it also needs to be below photochemical and photothermal limits known to cause ocular damage. The maximal permissible exposure is determined by a variety of factors, including wavelength, exposure duration, visual angle, pupil size, pulse width, pulse pattern, and repetition frequency. In this paper, we develop utilities to systematically and efficiently assess the contributions of these parameters in relation to the limits, following directly from the 2014 American National Standards Institute (ANSI). We also provide an array of stimulus protocols that fall within the bounds of both safety and effectiveness. Additional verification of safety is provided with a case study in rats using one of these protocols. PMID- 26882976 TI - Identification of a novel protein interaction between Elmo1 and Cdc27. AB - Elmo has no intrinsic catalytic activity but coordinate multiple cellular processes via their interactions with other proteins. Studies thus have been focused on identifying Elmo binding partners, but the number of characterized Elmo-interacting proteins remains limited. Here, we report Cdc27 as a novel Elmo1 interacting protein. In yeast and mammalian cells, Cdc27 specifically interacted with the C-terminal region of Elmo1 essential for Dock1 association and function. The interaction of Elmo1 with Dock1 abrogated binding between Elmo1 and Cdc27, but the Dock1-Elmo1 interaction was unaffected by Cdc27. Similarly, cellular phagocytotic functions mediated by the Elmo1-Dock1-Rac module were unaffected by Cdc27 levels. In summary, a novel binding partner, Cdc27, was identified for Elmo1 and they appear to be independent of Elmo-Dock1-Rac-mediated processes. PMID- 26882977 TI - Molecular evidence for the coordination of nitrogen and carbon metabolisms, revealed by a study on the transcriptional regulation of the agl3EFG operon that encodes a putative carbohydrate transporter in Streptomyces coelicolor. AB - In the agl3EFGXYZ operon (SCO7167-SCO7162, abbreviated as agl3 operon) of Streptomyces coelicolor M145, agl3EFG genes encode a putative ABC-type carbohydrate transporter. The transcription of this operon has been proved to be repressed by Agl3R (SCO7168), a neighboring GntR-family regulator, and this repression can be released by growth on poor carbon sources. Here in this study, we prove that the transcription of agl3 operon is also directly repressed by GlnR, a central regulator governing the nitrogen metabolism in S. coelicolor. The electrophoretic mobility shift assay (EMSA) employing the agl3 promoter and mixtures of purified recombinant GlnR and Agl3R indicates that GlnR and Agl3R bind to different DNA sequences within the promoter region of agl3 operon, which is further confirmed by the DNase I footprinting assay. As Agl3R and GlnR have been demonstrated to sense the extracellular carbon and nitrogen supplies, respectively, it is hypothesized that the transcription of agl3 operon is stringently governed by the availabilities of extracellular carbon and nitrogen sources. Consistent with the hypothesis, the agl3 operon is further found to be derepressed only under the condition of poor carbon and rich nitrogen supplies, when both regulators are inactivated. It is believed that activation of the expression of agl3 operon may facilitate the absorption of extracellular carbohydrates to balance the ratio of intracellular carbon to nitrogen. PMID- 26882978 TI - Depletion of Rab32 decreases intracellular lipid accumulation and induces lipolysis through enhancing ATGL expression in hepatocytes. AB - Nonalcoholic fatty liver disease (NAFLD) is a disease caused by the accumulation of lipids in hepatocytes. To date, however, the pathogenesis of NAFLD is still unclear. Recent studies have shown that Rab GTPases, a major protein family in vesicle trafficking, are associated with intracellular lipid accumulation. Here, we show that Rab32, the only Rab GTPase located in mitochondria, participates in hepatic steatosis. Ablation of Rab32 can decrease intracellular lipid accumulation in hepatocytes (HepG2, L02). Further studying the possible mechanism, we found that knockdown of Rab32 can enhance lipolysis instead of lipogenesis via inducing the expression of adipose triglyceride lipase (ATGL), a key enzyme on the surface of lipid droplets which has been proved to be significant in controlling intracellular lipid accumulation. Co immunoprecipitation shows that Rab32 and ATGL are not directly associated. These findings suggest that knockdown of Rab32 indirectly affects lipolysis through increasing the expression of ATGL. Taken together, our study reveals that Rab32 can participate in regulating intracellular lipid accumulation and that knockdown of Rab32 can decrease intracellular lipid accumulation in hepatocytes. We also demonstrated that ablation of Rab32 can induce intracellular lipolysis by enhancing the expression of ATGL. PMID- 26882979 TI - Absent Left Main Coronary Artery and Separate Ostia of Left Coronary System in a Patient with Holt-Oram Syndrome and Sinus Node Dysfunction. AB - BACKGROUND: Holt-Oram syndrome (HOS) is a rare but significant syndrome consisting of structural heart defects, conduction abnormalities, and upper extremity anomalies. It was first described in the British Heart Journal in 1960 by Mary Holt and Samuel Oram as a report of atrial septal defect, conduction disturbances, and hand malformations occurring in family members. Patients can present with heart blocks or symptoms of underlying congenital heart defects. CASE REPORT: A 41-year-old man with Holt-Oram syndrome presented with seizure like activity and was found to have an underlying conduction disturbance. Physical exam showed bilateral atrophic upper extremities with anatomic disfiguration, and weakness of the intrinsic hand muscles. Cardiovascular exam revealed a slow heart rate with irregular rhythm. EKG showed sinus arrest with junctional escape rhythm. Cardiac catheterization revealed coronary anomalies, including absent left main coronary artery and separate ostia of the left anterior ascending and left circumflex coronary artery. Coronary arteries were patent. Following electrophysiology study, sick sinus syndrome and AV block were diagnosed, and the patient received implantation of a permanent pacemaker. CONCLUSIONS: This patient presented with a seizure-like episode attributed to hypoxia during asystole from an underlying cardiac conduction defect associated with Holt-Oram syndrome. Arrhythmias and heart blocks are seen in these patients, and conduction defects are highly associated with congenital heart defects. Holt Oram syndrome rarely presents with coronary artery anomalies. There is no reported case of separate coronary ostia and absent left main coronary artery. Prompt diagnosis is important since anomalies in coronary and upper extremity vasculature might be challenging for invasive procedures. PMID- 26882980 TI - Exposure to the toxic dinoflagellate Alexandrium catenella modulates juvenile oyster Crassostrea gigas hemocyte variables subjected to different biotic conditions. AB - The Pacific oyster Crassostrea gigas is an important commercial species cultured throughout the world. Oyster production practices often include transfers of animals into new environments that can be stressful, especially at young ages. This study was undertaken to determine if a toxic Alexandrium bloom, occurring repeatedly in French oyster beds, could modulate juvenile oyster cellular immune responses (i.e. hemocyte variables). We simulated planting on commercial beds by conducting a cohabitation exposure of juvenile, "specific pathogen-free" (SPF) oysters (naive from the environment) with previously field-exposed oysters to induce interactions with new microorganisms. Indeed, toxic Alexandrium spp. exposures have been reported to modulate bivalve interaction with specific pathogens, as well as physiological and immunological variables in bivalves. In summary, SPF oysters were subjected to an artificial bloom of Alexandrium catenella, simultaneously with a cohabitation challenge. Exposure to A. catenella, and thus to the paralytic shellfish toxins (PSTs) and extracellular bioactive compounds produced by this alga, induced higher concentration, size, complexity and reactive oxygen species (ROS) production of circulating hemocytes. Challenge by cohabitation with field-exposed oysters also activated these hemocyte responses, suggesting a defense response to new microorganism exposure. These hemocyte responses to cohabitation challenge, however, were partially inhibited by A. catenella exposure, which enhanced hemocyte mortality, suggesting either detrimental effects of the interaction of both stressors on immune capacity, or the implementation of an alternative immune strategy through apoptosis. Indeed, no infection with specific pathogens (herpesvirus OsHV-1 or Vibrio aesturianus) was detected. Additionally, lower PST accumulation in challenged oysters suggests a physiological impairment through alteration of feeding-related processes. Overall, results of this study show that a short-term exposure to A. catenella combined with an exposure to a modified microbial community inhibited some hemocyte responses, and likely compromised physiological condition of the juvenile oysters. PMID- 26882982 TI - "Early" thoracic duct ligation for chylothorax after esophagectomy means "now". PMID- 26882981 TI - Acute and Chronic Ophthalmic Involvement in Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis - A Comprehensive Review and Guide to Therapy. II. Ophthalmic Disease. AB - Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life. PMID- 26882984 TI - RhesusBase PopGateway: Genome-Wide Population Genetics Atlas in Rhesus Macaque. AB - Although population genetics studies have significantly accelerated the evolutionary and functional interrogations of genes and regulations, limited polymorphism data are available for rhesus macaque, the model animal closely related to human. Here, we report the first genome-wide effort to identify and visualize the population genetics profile in rhesus macaque. On the basis of the whole-genome sequencing of 31 independent macaque animals, we profiled a comprehensive polymorphism map with 46,146,548 sites. The allele frequency for each polymorphism site, the haplotype structure, as well as multiple population genetics parameters were then calculated on a genome-wide scale. We further developed a specific interface, the RhesusBase PopGateway, to facilitate the visualization of these annotations, and highlighted the applications of this highly integrative platform in clarifying the selection signatures of genes and regulations in the context of the primate evolution. Overall, the updated RhesusBase provides a comprehensive monkey population genetics framework for in depth evolutionary studies of human biology. PMID- 26882983 TI - Advances in Time Estimation Methods for Molecular Data. AB - Molecular dating has become central to placing a temporal dimension on the tree of life. Methods for estimating divergence times have been developed for over 50 years, beginning with the proposal of molecular clock in 1962. We categorize the chronological development of these methods into four generations based on the timing of their origin. In the first generation approaches (1960s-1980s), a strict molecular clock was assumed to date divergences. In the second generation approaches (1990s), the equality of evolutionary rates between species was first tested and then a strict molecular clock applied to estimate divergence times. The third generation approaches (since ~2000) account for differences in evolutionary rates across the tree by using a statistical model, obviating the need to assume a clock or to test the equality of evolutionary rates among species. Bayesian methods in the third generation require a specific or uniform prior on the speciation-process and enable the inclusion of uncertainty in clock calibrations. The fourth generation approaches (since 2012) allow rates to vary from branch to branch, but do not need prior selection of a statistical model to describe the rate variation or the specification of speciation model. With high accuracy, comparable to Bayesian approaches, and speeds that are orders of magnitude faster, fourth generation methods are able to produce reliable timetrees of thousands of species using genome scale data. We found that early time estimates from second generation studies are similar to those of third and fourth generation studies, indicating that methodological advances have not fundamentally altered the timetree of life, but rather have facilitated time estimation by enabling the inclusion of more species. Nonetheless, we feel an urgent need for testing the accuracy and precision of third and fourth generation methods, including their robustness to misspecification of priors in the analysis of large phylogenies and data sets. PMID- 26882985 TI - Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration. AB - Characteristics of pseudogene degeneration at the coding level are well-known, such as a shift toward neutral rates of nonsynonymous substitutions and gain of frameshift mutations. In contrast, degeneration of pseudogene transcriptional regulation is not well understood. Here, we test two predictions of regulatory degeneration along a pseudogenized lineage: 1) Decreased transcription factor (TF) binding and 2) accelerated evolution in putative cis-regulatory regions.We find evidence for decreased TF binding levels nearby two primate pseudogenes compared with functional liver genes. However, the majority of TF-bound sequences nearby pseudogenes do not show evidence for lineage-specific accelerated rates of evolution. We conclude that decreases in TF binding level could be a marker for regulatory degeneration, while sequence degeneration in primate cis-regulatory modules may be obscured by background rates of TF binding site turnover. PMID- 26882988 TI - Laser-initiated primary and secondary nuclear reactions in Boron-Nitride. AB - Nuclear reactions initiated by laser-accelerated particle beams are a promising new approach to many applications, from medical radioisotopes to aneutronic energy production. We present results demonstrating the occurrence of secondary nuclear reactions, initiated by the primary nuclear reaction products, using multicomponent targets composed of either natural boron (B) or natural boron nitride (BN). The primary proton-boron reaction (p + (11)B -> 3 alpha + 8.7 MeV), is one of the most attractive aneutronic fusion reaction. We report radioactive decay signatures in targets irradiated at the Elfie laser facility by laser accelerated particle beams which we interpret as due to secondary reactions induced by alpha (alpha) particles produced in the primary reactions. Use of a second nanosecond laser beam, adequately synchronized with the short laser pulse to produce a plasma target, further enhanced the reaction rates. High rates and chains of reactions are essential for most applications. PMID- 26882986 TI - Compensating the Fitness Costs of Synonymous Mutations. AB - Synonymous mutations do not change the sequence of the polypeptide but they may still influence fitness. We investigated in Salmonella enterica how four synonymous mutations in the rpsT gene (encoding ribosomal protein S20) reduce fitness (i.e., growth rate) and the mechanisms by which this cost can be genetically compensated. The reduced growth rates of the synonymous mutants were correlated with reduced levels of the rpsT transcript and S20 protein. In an adaptive evolution experiment, these fitness impairments could be compensated by mutations that either caused up-regulation of S20 through increased gene dosage (due to duplications), increased transcription of the rpsT gene (due to an rpoD mutation or mutations in rpsT), or increased translation from the rpsT transcript (due to rpsT mutations). We suggest that the reduced levels of S20 in the synonymous mutants result in production of a defective subpopulation of 30S subunits lacking S20 that reduce protein synthesis and bacterial growth and that the compensatory mutations restore S20 levels and the number of functional ribosomes. Our results demonstrate how specific synonymous mutations can cause substantial fitness reductions and that many different types of intra- and extragenic compensatory mutations can efficiently restore fitness. Furthermore, this study highlights that also synonymous sites can be under strong selection, which may have implications for the use of dN/dS ratios as signature for selection. PMID- 26882990 TI - External characteristic determination of eggs and cracked eggs identification using spectral signature. AB - This study was carried out to use hyperspectral imaging technique for determining color (L*, a* and b*) and eggshell strength and identifying cracked chicken eggs. Partial least squares (PLS) models based on full and selected wavelengths suggested by regression coefficient (RC) method were established to predict the four parameters, respectively. Partial least squares-discriminant analysis (PLS DA) and RC-partial least squares-discriminant analysis (RC-PLS-DA) models were applied to identify cracked eggs. PLS models performed well with the correlation coefficient (rp) of 0.788 for L*, 0.810 for a*, 0.766 for b* and 0.835 for eggshell strength. RC-PLS models also obtained the rp of 0.771 for L*, 0.806 for a*, 0.767 for b* and 0.841 for eggshell strength. The classification results were 97.06% in PLS-DA model and 88.24% in RC-PLS-DA model. It demonstrated that hyperspectral imaging technique has the potential to be used to detect color and eggshell strength values and identify cracked chicken eggs. PMID- 26882987 TI - R2d2 Drives Selfish Sweeps in the House Mouse. AB - A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID- 26882989 TI - Hepatocyte TRAF3 promotes liver steatosis and systemic insulin resistance through targeting TAK1-dependent signalling. AB - Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. Here we show that tumour necrosis factor receptor-associated factor 3 (TRAF3) is upregulated in mouse and human livers with hepatic steatosis. After 24 weeks on a high-fat diet (HFD), obesity, insulin resistance, hepatic steatosis and inflammatory responses are significantly ameliorated in liver-specific TRAF3-knockout mice, but exacerbated in transgenic mice overexpressing TRAF3 in hepatocytes. The detrimental effects of TRAF3 on hepatic steatosis and related pathologies are confirmed in ob/ob mice. We further show that in response to HFD, hepatocyte TRAF3 binds to TGF-beta-activated kinase 1 (TAK1) to induce TAK1 ubiquitination and subsequent autophosphorylation, thereby enhancing the activation of downstream IKKbeta-NF-kappaB and MKK-JNK-IRS1(307) signalling cascades, while disrupting AKT-GSK3beta/FOXO1 signalling. The TRAF3-TAK1 interaction and TAK1 ubiquitination are indispensable for TRAF3-regulated hepatic steatosis. In conclusion, hepatocyte TRAF3 promotes HFD-induced or genetic hepatic steatosis in a TAK1-dependent manner. PMID- 26882991 TI - Early malnutrition results in long-lasting impairments in pattern-separation for overlapping novel object and novel location memories and reduced hippocampal neurogenesis. AB - Numerous epidemiological studies indicate that malnutrition during in utero development and/or childhood induces long-lasting learning disabilities and enhanced susceptibility to develop psychiatric disorders. However, animal studies aimed to address this question have yielded inconsistent results due to the use of learning tasks involving negative or positive reinforces that interfere with the enduring changes in emotional reactivity and motivation produced by in utero and neonatal malnutrition. Consequently, the mechanisms underlying the learning deficits associated with malnutrition in early life remain unknown. Here we implemented a behavioural paradigm based on the combination of the novel object recognition and the novel object location tasks to define the impact of early protein-restriction on the behavioural, cellular and molecular basis of memory processing. Adult rats born to dams fed a low-protein diet during pregnancy and lactation, exhibited impaired encoding and consolidation of memory resulting from impaired pattern separation. This learning deficit was associated with reduced production of newly born hippocampal neurons and down regulation of BDNF gene expression. These data sustain the existence of a causal relationship between early malnutrition and impaired learning in adulthood and show that decreased adult neurogenesis is associated to the cognitive deficits induced by childhood exposure to poor nutrition. PMID- 26882992 TI - Long-term safety and stability of angiogenesis induced by balanced single-vector co-expression of PDGF-BB and VEGF164 in skeletal muscle. AB - Therapeutic angiogenesis by growth factor delivery is an attractive treatment strategy for ischemic diseases, yet clinical efficacy has been elusive. The angiogenic master regulator VEGF-A can induce aberrant angiogenesis if expressed above a threshold level. Since VEGF remains localized in the matrix around expressing cells, homogeneous dose distribution in target tissues is required, which is challenging. We found that co-expression of the pericyte-recruiting factor PDGF-BB at a fixed ratio with VEGF from a single bicistronic vector ensured normal angiogenesis despite heterogeneous high VEGF levels. Taking advantage of a highly controlled gene delivery platform, based on monoclonal populations of transduced myoblasts, in which every cell stably produces the same amount of each factor, here we rigorously investigated a) the dose-dependent effects, and b) the long-term safety and stability of VEGF and PDGF-BB co expression in skeletal muscle. PDGF-BB co-expression did not affect the normal angiogenesis by low and medium VEGF doses, but specifically prevented vascular tumors by high VEGF, yielding instead normal and mature capillary networks, accompanied by robust arteriole formation. Induced angiogenesis persisted unchanged up to 4 months, while no tumors appeared. Therefore, PDGF-BB co expression is an attractive strategy to improve safety and efficacy of therapeutic angiogenesis by VEGF gene delivery. PMID- 26882993 TI - Mind-Wandering Tends to Occur under Low Perceptual Demands during Driving. AB - Fluctuations in attention behind the wheel poses a significant risk for driver safety. During transient periods of inattention, drivers may shift their attention towards internally-directed thoughts or feelings at the expense of staying focused on the road. This study examined whether increasing task difficulty by manipulating involved sensory modalities as the driver detected the lane-departure in a simulated driving task would promote a shift of brain activity between different modes of processing, reflected by brain network dynamics on electroencephalographic sources. Results showed that depriving the driver of salient sensory information imposes a relatively more perceptually demanding task, leading to a stronger activation in the task-positive network. When the vehicle motion feedback is available, the drivers may rely on vehicle motion to perceive the perturbations, which frees attentional capacity and tends to activate the default mode network. Such brain network dynamics could have major implications for understanding fluctuations in driver attention and designing advance driver assistance systems. PMID- 26882994 TI - Spin noise explores local magnetic fields in a semiconductor. AB - Rapid development of spin noise spectroscopy of the last decade has led to a number of remarkable achievements in the fields of both magnetic resonance and optical spectroscopy. In this report, we demonstrate a new - magnetometric - potential of the spin noise spectroscopy and use it to study magnetic fields acting upon electron spin-system of an n-GaAs layer in a high-Q microcavity probed by elliptically polarized light. Along with the external magnetic field, applied to the sample, the spin noise spectrum revealed the Overhauser field created by optically oriented nuclei and an additional, previously unobserved, field arising in the presence of circularly polarized light. This "optical field" is directed along the light propagation axis, with its sign determined by sign of the light helicity. We show that this field results from the optical Stark effect in the field of the elliptically polarized light. This conclusion is supported by theoretical estimates. PMID- 26882995 TI - Longitudinal spin separation of light and its performance in three-dimensionally controllable spin-dependent focal shift. AB - Spin Hall effect of light, which is normally explored as a transverse spin dependent separation of a light beam, has attracted enormous research interests. However, it seems there is no indication for the existence of the longitudinal spin separation of light. In this paper, we propose and experimentally realize the spin separation along the propagation direction by modulating the Pancharatnam-Berry (PB) phase. Due to the spin-dependent divergence and convergence determined by the PB phase, a focused Gaussian beam could split into two opposite spin states, and focuses at different distances, representing the longitudinal spin separation. By combining this longitudinal spin separation with the transverse one, we experimentally achieve the controllable spin-dependent focal shift in three dimensional space. This work provides new insight on steering the spin photons, and is expected to explore novel applications of optical trapping, manipulating, and micromachining with higher degree of freedom. PMID- 26882997 TI - Kinetics of a Multilamellar Lipid Vesicle Ripening: Simulation and Theory. AB - Lipid vesicle ripening via unimolecular diffusion and exchange greatly influences the evolution of complex vesicle structure. However, this behavior is difficult to capture using conventional experimental technology and molecular simulation. In the present work, the ripening of a multilamellar lipid vesicle (MLV) is effectively explored using a mesoscale coarse-grained molecular model. The simulation reveals that a small MLV evolves into a unilamellar vesicle over a very long time period. In this process, only the outermost bilayer inflates, and the inner bilayers shrink. With increasing MLV size, the ripening process becomes complex and depends on competition between a series of adjacent bilayers in the MLV. To understand the diffusion behavior of the unimolecule, the potentials of mean force (PMFs) of a single lipid molecule across unilamellar vesicles with different sizes are calculated. It is found that the PMF of lipid dissociation from the inner layer is different than that of the outer layer, and the dissociation energy barrier sensitively depends on the curvature of the bilayer. A kinetics theoretical model of MLV ripening that considers the lipid dissociation energy for curved bilayers is proposed. The model successfully interprets the MLV ripening process with various numbers of bilayers and shows potential to predict the ripening kinetics of complex lipid vesicles. PMID- 26882996 TI - Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response. AB - Acute myocardial infarction induces activation of the acute phase response and infiltration of leukocytes to the infarcted area. Moreover, myocardium that is remote from ischemic area also becomes inflamed. Inflammatory reaction clears dead cells and matrix debris, while prolongation or expansion of the inflammatory response results in dysfunction following myocardial infarction. Wnt glycolipoproteins are best characterized as regulators of embryonic development. Recently several reports suggest that they also contribute to the inflammatory response in adult animals. However, the effects of Wnt proteins on myocardial infarction have not been explored. Here we show that Wnt11 expression leads to significant improvements of survival and cardiac function by suppressing infiltration of multiple kinds of inflammatory cells in infarcted heart. Wnt11 protein suppresses gene expression of inflammatory cytokines through the modulation of NF-kappaB in vitro. These results reveal a novel function of Wnt11 in the regulation of inflammatory response and provide a rationale for the use of Wnt11 to manipulate human diseases that are mediated by inflammation. PMID- 26882998 TI - DNA replication: SUMO wrestling to get the timing right. PMID- 26883004 TI - Ageing: Anti-ageing formula. PMID- 26883005 TI - Computer-Aided Molecular Design of Bis-phosphine Oxide Lanthanide Extractants. AB - Computer-aided molecular design and high-throughput screening of viable host architectures can significantly reduce the efforts in the design of novel ligands for efficient extraction of rare earth elements. This paper presents a computational approach to the deliberate design of bis-phosphine oxide host architectures that are structurally organized for complexation of trivalent lanthanides. Molecule building software, HostDesigner, was interfaced with molecular mechanics software, PCModel, providing a tool for generating and screening millions of potential R2(O)P-link-P(O)R2 ligand geometries. The molecular mechanics ranking of ligand structures is consistent with both the solution-phase free energies of complexation obtained with density functional theory and the performance of known bis-phosphine oxide extractants. For the case where the link is -CH2-, evaluation of the ligand geometry provides the first characterization of a steric origin for the "anomalous aryl strengthening" effect. The design approach has identified a number of novel bis-phosphine oxide ligands that are better organized for lanthanide complexation than previously studied examples. PMID- 26883007 TI - Fox Chase Cancer Center's Genitourinary Division: a national resource for research, innovation and patient care. AB - Founded in 1904, Fox Chase Cancer Center remains committed to its mission. It is one of 41 centers in the country designated as a Comprehensive Cancer Center by the National Cancer Institute, is a founding member of the National Comprehensive Cancer Network, holds the magnet designation for nursing excellence, is one of the first to establish a family cancer risk assessment program, and has achieved national distinction because of the scientific discoveries made there that have advanced clinical care. Two of its researchers have won Nobel prizes. The Genitourinary Division is nationally recognized and viewed as one of the top driving forces behind the growth of Fox Chase due to its commitment to initiating and participating in clinical trials, its prolific contributions to peer-reviewed publications and presentations at scientific meetings, its innovations in therapies and treatment strategies, and its commitment to bringing cutting-edge therapies to patients. PMID- 26883006 TI - Structural Characterization and Immunomodulatory Activity of a Novel Polysaccharide from Lepidium meyenii. AB - A novel polysaccharide named as MC-1 was isolated from the roots of Lepidium meyenii using a water extraction method. Structural characterization revealed that MC-1 had an average molecular weight of 11.3 kDa and consisted of arabinose (26.21%), mannose (11.81%), glucose (53.66%), and galactose (8.32%). The main linkage types of MC-1 were proven to be (1 -> 5)-alpha-L-Ara, (1 -> 3)-alpha-L Man, (1 -> 2,6)-alpha-L-Man, (1 -> )-alpha-D-Glc, (1 -> 4)-alpha-D-Glc, (1 -> 6) alpha-D-Glc and (1 -> 6)-beta-D-Gal by methylation analysis, periodate oxidation Smith degradation and NMR analysis. The immunostimulating assay indicated that MC 1 could significantly enhance the pinocytic and phagocytic capacity and promote the NO, TNF-alpha, and IL-6 secretion of RAW 264.7 cells, involving toll-like receptor 2, complement receptor 3, and mannose receptor mainly. These results suggested the potential utilization of MC-1 as an attractive functional food supplement candidate for hypoimmunity population. PMID- 26883003 TI - A decade of transcription factor-mediated reprogramming to pluripotency. AB - The past 10 years have seen great advances in our ability to manipulate cell fate, including the induction of pluripotency in vitro to generate induced pluripotent stem cells (iPSCs). This process proved to be remarkably simple from a technical perspective, only needing the host cell and a defined cocktail of transcription factors, with four factors - octamer-binding protein 3/4 (OCT3/4), SOX2, Kruppel-like factor 4 (KLF4) and MYC (collectively referred to as OSKM) - initially used. The mechanisms underlying transcription factor-mediated reprogramming are still poorly understood; however, several mechanistic insights have recently been obtained. Recent years have also brought significant progress in increasing the efficiency of this technique, making it more amenable to applications in the fields of regenerative medicine, disease modelling and drug discovery. PMID- 26883001 TI - Molecular features of cellular reprogramming and development. AB - Differentiating somatic cells are progressively restricted to specialized functions during ontogeny, but they can be experimentally directed to form other cell types, including those with complete embryonic potential. Early nuclear reprogramming methods, such as somatic cell nuclear transfer (SCNT) and cell fusion, posed significant technical hurdles to precise dissection of the regulatory programmes governing cell identity. However, the discovery of reprogramming by ectopic expression of a defined set of transcription factors, known as direct reprogramming, provided a tractable platform to uncover molecular characteristics of cellular specification and differentiation, cell type stability and pluripotency. We discuss the control and maintenance of cellular identity during developmental transitions as they have been studied using direct reprogramming, with an emphasis on transcriptional and epigenetic regulation. PMID- 26883008 TI - MicroRNA-365a-3p promotes tumor growth and metastasis in laryngeal squamous cell carcinoma. AB - MicroRNAs (miRNAs) are increasingly recognized as oncogenes or tumor suppressors in laryngeal squamous cell carcinoma (LSCC). In this study, we analyzed the roles of miR-365a-3p, miR-143-5p, and miR-494-3p in LSCC using Annexin V/propidium iodide double staining and flow cyto-metry, along with a Transwell migration and invasion assay. The results showed that miR-365a-3p inhibitor significantly facilitated cell apoptosis and suppressed cell cycle progression, migration, and invasion in Hep-2 cells. However, miR-143-5p and miR-494-3p had no such influences. We then investigated the role of miR-365a-3p in LSCC in vivo and found that miR-365a-3p inhibitor suppressed LSCC xenograft tumor growth and metastasis in xenograft mouse models. Moreover, miR-365a-3p inhibitor significantly decreased the expression of p-AKT (Ser473), which indicated that miR-365a-3p can mediate PI3K/AKT signaling pathway transduction via p-AKT (Ser473) in LSCC. The data suggest that miR-365a-3p may act as an oncomiR and may promote growth and metastasis in LSCC via the PI3K/AKT signaling pathway, and thus miR-365a-3p may be a potential therapeutic target for treatment of LSCC. PMID- 26883010 TI - Reliability and validity of the Lower Limb Function Questionnaire when completed by young adult orthotic and prosthetic device users. AB - Purpose The Lower Limb Function Questionnaire (LLFQ) was developed as a self report assessment of lower-limb functional ability for orthotic and prosthetic (O&P) device users to be suitable for a wide range of conditions, cultures, and ages. The measure aims to address an existing gap in tools for the assessment of functional ability in this population. The purpose of this study is to evaluate LLFQ reliability and validity in a sample of young adult O&P users. Methods Adolescents from a secondary school in Kenya completed the LLFQ twice, 6 d apart, and test-retest reliability was assessed using intra-class correlation coefficients. Validity evaluations involved Timed Up-and-Go, 6-min walk, 6-min obstacle course, and/or spatiotemporal gait assessments. Oxygen consumption was measured during walk tests. Associations between the LLFQ and each measure were evaluated using Pearson correlation coefficients for construct validity. Results LLFQ reliability was acceptable (ICC = 0.79, 95% CIs 0.64-0.89). Construct validity was demonstrated via moderate correlation (r > 0.60) with obstacle course distance, gait velocity, stride length, and stance/single support/double support percent of gait cycle. Conclusions Both LLFQ reliability and validity were acceptable in the sample of youth in Kenya. Further testing is required to determine applicability in other cultural contexts. Implications for Rehabilitation The LLFQ may be clinically useful across a variety of cultures and conditions to provide feedback on the effectiveness of rehabilitative treatment or assistive devices for youth with lower limb impairments. The LLFQ may enable specific strengths and challenges to lower limb function to be identified to enable planning of well-targeted rehabilitation. PMID- 26883011 TI - Domain configurations in Co/Pd and L10-FePt nanowire arrays with perpendicular magnetic anisotropy. AB - Perpendicular magnetic anisotropy [Co/Pd]15 and L10-FePt nanowire arrays of period 63 nm with linewidths 38 nm and 27 nm and film thickness 27 nm and 20 nm respectively were fabricated using a self-assembled PS-b-PDMS diblock copolymer film as a lithographic mask. The wires are predicted to support Neel walls in the Co/Pd and Bloch walls in the FePt. Magnetostatic interactions from nearest neighbor nanowires promote a ground state configuration consisting of alternating up and down magnetization in adjacent wires. This was observed over ~75% of the Co/Pd wires after ac-demagnetization but was less prevalent in the FePt because the ratio of interaction field to switching field was much smaller. Interactions also led to correlations in the domain wall positions in adjacent Co/Pd nanowires. The reversal process was characterized by nucleation of reverse domains, followed at higher fields by propagation of the domains along the nanowires. These narrow wires provide model system for exploring domain wall structure and dynamics in perpendicular anisotropy systems. PMID- 26883009 TI - Multiple syndemic psychosocial factors are associated with reduced engagement in HIV care among a multinational, online sample of HIV-infected MSM in Latin America. AB - Latin America has some of the highest levels of antiretroviral therapy (ART) coverage of any developing region in the world. Early initiation and optimal adherence to ART are necessary for improved health outcomes and reduction in onward transmission. Previous work has demonstrated the role of psychosocial problems as barriers to uptake and adherence to ART, and recently, a syndemic framework has been applied to the role of multiple psychosocial syndemic factors and adherence to ART, in the USA. However, to our knowledge, these associations have not been investigated outside of the USA, nor in a multi-country context. To address these gaps, we assessed the association between multiple co-occurring psychosocial factors and engagement in HIV-related medical care and adherence to ART among a large, multinational sample of sexually-active HIV-infected men who have sex with men in Latin America. Among the 2020 respondents, 80.7% reported currently receiving HIV-related medical care, 72.3% reported currently receiving ART; among those, 62.5% reported 100% adherence. Compared with experiencing no psychosocial health problems, experiencing five or more psychosocial health problems is associated with 42% lower odds of currently receiving HIV-related medical care (adjusted odds ratio, aOR = 0.58, 95% CI 0.36, 0.95) and of currently receiving ART (aOR = 0.58, 95% CI 0.38, 0.91). The number of psychosocial health problems experienced was associated with self-reported ART adherence in a dose-response relationship; compared to those with none of the factors, individuals with one syndemic factor had 23% lower odds (aOR = 0.77, 95% CI 0.60, 0.97) and individuals with five or more syndemic factors had 72% lower odds (aOR = 0.28, 95% CI 0.14, 0.55) of reporting being 100% adherent to ART. Addressing co-occurring psychosocial problems as potential barriers to uptake and adherence of ART in Latin America may improve the effectiveness of secondary prevention interventions. PMID- 26883012 TI - Correlates of depressive symptoms in individuals attending outpatient stroke clinics. AB - Background and purpose Depressive symptoms are common post-stroke. We examined stroke deficits and lifestyle factors that are independent predictors for depressive symptomology. Methods A retrospective chart review was performed for patients' post-stroke who attended outpatient clinics at a hospital in Southwestern Ontario between 1 January 2014 and 30 September 2014. Demographic variables, stroke deficits, secondary stroke risk factors and disability study measures [Patient Health Questionnaire-9 (PHQ-9) and Montreal Cognitive Assessment (MoCA)] were analyzed. Results Of the 221 outpatients who attended the stroke clinics (53% male; mean age = 65.2 +/- 14.9 years; mean time post-stroke 14.6 +/- 20.1 months), 202 patients were used in the final analysis. About 36% of patients (mean = 5.17 +/- 5.96) reported mild to severe depressive symptoms (PHQ 9 >= 5). Cognitive impairment (CI), smoking, pain and therapy enrollment (p < 0.01) were significantly associated with depressive symptoms. Patients reporting CI were 4 times more likely to score highly on the PHQ-9 than those who did not report CI (OR = 4.72). While controlling for age, MoCA scores negatively related to depressive symptoms with higher PHQ-9 scores associated with lower MoCA scores (r= -0.39, p < 0.005). Conclusions High levels of depressive symptoms are common in the chronic phase post-stroke and were partially related to cognition, pain, therapy enrollment and lifestyle factors. Implications for Rehabilitation Stroke patients who report cognitive deficits, pain, tobacco use or being enrolled in therapy may experience increased depressive symptoms. A holistic perspective of disease and lifestyle factors should be considered while assessing risk of depressive symptoms in stroke patients. Patients at risk for depressive symptoms should be monitored at subsequent outpatient visits. PMID- 26883013 TI - Long-term costs of colorectal cancer treatment in Spain. AB - BACKGROUND: Assessing the long-term cost of colorectal cancer (CRC) increases our understanding of the disease burden. The aim of this paper is to estimate the long-term costs of CRC care by stage at diagnosis and phase of care in the Spanish National Health Service. METHODS: Retrospective study on resource use and direct medical cost of a cohort of 699 patients diagnosed and treated for CRC in 2000-2006, with follow-up until 30 June 2011, at Hospital del Mar (Barcelona). The Kaplan-Meier sample average estimator was used to calculate observed 11-year costs, which were then extrapolated to 16 years. Bootstrap percentile confidence intervals were calculated for the mean long-term cost per patient by stage. Phase specific, long-term costs for the entire CRC cohort were also estimated. RESULTS: With regard to stage at diagnosis, the mean long-term cost per patient ranged from ?20,708 (in situ) to ?47,681 (stage III). The estimated costs increased at more advanced stages up to stage III and then substantially decreased in stage IV. In terms of treatment phase, the mean cost of the initial period represented 24.8 % of the total mean long-term cost, whereas the cost of continuing and advanced care phases represented 16.9 and 58.3 %, respectively. CONCLUSIONS: This study is the first to provide long-term cost estimates for CRC treatment, by stage at diagnosis and phase of care, based on data from clinical practice in Spain, and it will contribute useful information for future studies on cost effectiveness and budget impact of different therapeutic innovations in Spain. PMID- 26883014 TI - Variation in 5-hydroxymethylcytosine across human cortex and cerebellum. AB - BACKGROUND: The most widely utilized approaches for quantifying DNA methylation involve the treatment of genomic DNA with sodium bisulfite; however, this method cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Previous studies have shown that 5hmC is enriched in the brain, although little is known about its genomic distribution and how it differs between anatomical regions and individuals. In this study, we combine oxidative bisulfite (oxBS) treatment with the Illumina Infinium 450K BeadArray to quantify genome wide patterns of 5hmC in two distinct anatomical regions of the brain from multiple individuals. RESULTS: We identify 37,145 and 65,563 sites passing our threshold for detectable 5hmC in the prefrontal cortex and cerebellum respectively, with 23,445 loci common across both brain regions. Distinct patterns of 5hmC are identified in each brain region, with notable differences in the genomic location of the most hydroxymethylated loci between these brain regions. Tissue-specific patterns of 5hmC are subsequently confirmed in an independent set of prefrontal cortex and cerebellum samples. CONCLUSIONS: This study represents the first systematic analysis of 5hmC in the human brain, identifying tissue-specific hydroxymethylated positions and genomic regions characterized by inter-individual variation in DNA hydroxymethylation. This study demonstrates the utility of combining oxBS-treatment with the Illumina 450k methylation array to systematically quantify 5hmC across the genome and the potential utility of this approach for epigenomic studies of brain disorders. PMID- 26883015 TI - Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer. AB - BACKGROUND: The bone scan index (BSI), which is obtained using a computer-aided bone scan evaluation system, is anticipated to become an objective and quantitative clinical tool for evaluating bone metastases in prostate cancer. Here, we assessed the usefulness of the BSI as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated using docetaxel. METHODS: We analyzed 41 patients who received docetaxel for mCRPC. The Bonenavi system was used as the calculation program for the BSI. The utility of the BSI as a predictor of overall survival (OS) after docetaxel was evaluated. The Cox proportional hazards model was used to investigate the association between clinical variables obtained at docetaxel treatment, namely PSA, patient age, liver metastasis, local therapy, hemoglobin (Hb), lactase dehydrogenase (LDH), albumin (Alb), PSA doubling time, and BSI and OS. RESULTS: The median OS after docetaxel therapy was 17.7 months. Death occurred in 22 (53.7%) patients; all deaths were caused by prostate cancer. In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for OS after docetaxel; these were liver metastases (yes vs no; HR, 3.681; p = 0.026), Alb (<3.9 vs >= 3.9; HR, 3.776; p = 0.020), and BSI (>1% vs <= 1%; HR, 3.356; p = 0.037). We evaluated the discriminatory ability of our models including or excluding the BSI by quantifying the c-index. The BSI improved the c-index from 0.758 to 0.769 for OS after docetaxel. CRPC patients with a BSI >1 had a significantly shorter OS than patients with a BSI <= 1 (p = 0.029). CONCLUSIONS: The BSI, liver metastases and Alb were independent prognostic factors for OS after docetaxel. The BSI might be a useful tool for risk stratification of mCRPC patients undergoing docetaxel treatment. PMID- 26883018 TI - Mothers and Fathers Both Matter: The Positive Influence of Parental Physical Activity Modelling on Children's Leisure-Time Physical Activity. AB - PURPOSE: To investigate associations between maternal and paternal sport participation, and children's leisure-time physical activity, and to explore differences by child gender. METHOD: The sample comprised 737 year five students (mean age: 11.0 +/- 0.6 years, 52% male) recruited through the Fit for Pisa Project which was conducted in 2008 at 6 secondary schools in Goettingen, Germany. Maternal and paternal sport participation were assessed through child reports of mothers' and fathers' weekly participation in sport. Children's leisure-time physical activity was measured as minutes/week that children engaged in organized and nonorganized sport. Multiple linear regression was used to assess associations between maternal and paternal sport participation, and children's leisure-time physical activity. RESULTS: Both maternal and paternal sport participation were positively associated with children's leisure-time physical activity (maternal: b = 34.20, p < .001; paternal: b = 25.32, p < .05). When stratifying analyses by child gender, maternal sport participation remained significantly associated with leisure-time physical activity in girls (b = 60.64, p < .001). In contrast, paternal sport participation remained significantly associated with leisure-time physical activity in boys (b = 43.88, p < .01). CONCLUSION: Both maternal and paternal modeling positively influence children's leisure-time physical activity. PMID- 26883017 TI - C14orf166 overexpression correlates with tumor progression and poor prognosis of breast cancer. AB - BACKGROUND: Chromosome 14 open reading frame 166 (C14orf166) is upregulated in various tumors, but its role in breast cancer has not been reported. METHODS: Quantitative real-time PCR and western blot were used to determine C14orf166 expression in normal breast epithelial cells (NBEC), breast cancer cells, and four matched pairs of breast cancer tissues and adjacent noncancerous tissues. Using immunohistochemistry, we determined C14orf166 expression in paraffin embedded tissues from 121 breast cancer patients. Statistical analyses were performed to examine the associations among C14or166 expression, clinicopathological parameters and prognosis outcome of breast cancer. MTT and colony formation assay were used to determine the effect of C14orf166 on cell proliferation by overexpression or knockdown of C14orf166 level. RESULTS: C14orf166 was upregulated in breast cancer cell lines and tissues compared with the normal cells and adjacent normal breast tissues, high C14orf166 expression was positively with advancing clinical stage. The correlation analysis between C14orf166 expression and clinicopathological characteristics suggested C14orf166 expression was significantly correlated with clinical stages, T classification, N classification and PR expression, Kaplan-Meier curves with log rank tests showed patients with low C14orf166 expression had better survival, Cox-regression analysis suggested C14orf166 was an unfavorable prognostic factor for breast cancer patients. C14orf166 overexpression promoted breast cancer cell proliferation, whereas knockdown of C14orf166 inhibited this effect. Further analysis found C14orf166 overexpression inhibited cell cycle inhibitors P21 and P27 expression, and increased the levels of Cyclin D1 and phosphorylation of Rb, suggesting C14orf166 contributed to cell proliferation by regulating G1/S transition. CONCLUSION: Our findings suggested C14orf166 could be a novel prognostic biomarker of breast cancer, it also contributes to cell proliferation by regulating G1/S transition. PMID- 26883016 TI - Comparison of transforming growth factor beta expression in healthy and diseased human tendon. AB - BACKGROUND: Diseased tendons are characterised by fibrotic scar tissue, which adversely affects tendon structure and function and increases the likelihood of re-injury. The mechanisms and expression profiles of fibrosis in diseased tendon is understudied compared to pulmonary and renal tissues, where transforming growth factor (TGF)beta and its associated superfamily are known to be key drivers of fibrosis and modulate extracellular matrix homeostasis. We hypothesised that differential expression of TGFbeta superfamily members would exist between samples of human rotator cuff tendons with established disease compared to healthy control tendons. METHODS: Healthy and diseased rotator cuff tendons were collected from patients presenting to an orthopaedic referral centre. Diseased tendinopathic (intact) and healthy rotator cuff tendons were collected via ultrasound-guided biopsy and torn tendons were collected during routine surgical debridement. Immunohistochemistry and quantitative real-time polymerase chain reaction were used to investigate the protein and gene expression profiles of TGFbeta superfamily members in these healthy and diseased tendons. RESULTS: TGFbeta superfamily members were dysregulated in diseased compared to healthy tendons. Specifically, TGFbeta-1, TGFbeta receptor (R)1 and TGFbeta R2 proteins were reduced (p < 0.01) in diseased compared to healthy tendons. At the mRNA level, TGFbeta R1 was significantly reduced in samples of diseased tendons, whereas TGFbeta R2 was increased (p < 0.01). BMP-2, BMP-7 and CTGF mRNA remained unchanged with tendon disease. CONCLUSIONS: We propose that downregulation of TGFbeta pathways in established tendon disease may be a protective response to limit disease-associated fibrosis. The disruption of the TGFbeta axis with disease suggests associated downstream pathways may be important for maintaining healthy tendon homeostasis. The findings from our study suggest that patients with established tendon disease would be unlikely to benefit from therapeutic TGFbeta blockade, which has been investigated as a treatment strategy in several animal models. Future studies should investigate the expression profile of fibrotic mediators in earlier stages of tendon disease to improve understanding of the targetable mechanisms underpinning tendon fibrosis. PMID- 26883019 TI - Incidence and timing of potentially high-risk arrhythmias detected through long term continuous ambulatory electrocardiographic monitoring. AB - BACKGROUND: Ambulatory electrocardiographic (ECG) monitoring is the standard to screen for high-risk arrhythmias. We evaluated the clinical utility of a novel, leadless electrode, single-patient-use ECG monitor that stores up to 14 days of a continuous recording to measure the burden and timing of potentially high-risk arrhythmias. METHODS: We examined data from 122,815 long term continuous ambulatory monitors (iRhythm ZIO(r) Service, San Francisco) prescribed from 2011 to 2013 and categorized potentially high-risk arrhythmias into two types: (1) ventricular arrhythmias including non-sustained and sustained ventricular tachycardia and (2) bradyarrhythmias including sinus pauses >3 s, atrial fibrillation pauses >5 s, and high-grade heart block (Mobitz Type II or third degree heart block). RESULTS: Of 122,815 ZIO(r) recordings, median wear time was 9.9 (IQR 6.8-13.8) days and median analyzable time was 9.1 (IQR 6.4-13.1) days. There were 22,443 (18.3%) with at least one episode of non-sustained ventricular tachycardia (NSVT), 238 (0.2%) with sustained VT, 1766 (1.4%) with a sinus pause >3 s (SP), 520 (0.4%) with a pause during atrial fibrillation >5 s (AFP), and 1486 (1.2%) with high-grade heart block (HGHB). Median time to first arrhythmia was 74 h (IQR 26-149 h) for NSVT, 22 h (IQR 5-73 h) for sustained VT, 22 h (IQR 7 64 h) for SP, 31 h (IQR 11-82 h) for AFP, and 40 h (SD 10-118 h) for HGHB. CONCLUSIONS: A significant percentage of potentially high-risk arrhythmias are not identified within 48-h of ambulatory ECG monitoring. Longer-term continuous ambulatory ECG monitoring provides incremental detection of these potentially clinically relevant arrhythmic events. PMID- 26883020 TI - Any progress in pancreatic cancer? PMID- 26883021 TI - Access and utilisation of healthcare services in rural Tanzania: A comparison of public and non-public facilities using quality, equity, and trust dimensions. AB - This study compared the access and utilisation of health services in public and non-public health facilities in terms of quality, equity and trust in the Mbarali district, Tanzania. Interviews, focus group discussions, and informal discussions were used to generate data. Of the 1836 respondents, 1157 and 679 respondents sought healthcare services on their last visit at public or non-public health facilities, respectively. While 45.5% rated the quality of services to be good in both types of facilities, reported medicine shortages were more pronounced among those who visited public rather than non-public health facilities (OR = 1.7, 95% CI 1.4, 2.1). Respondents who visited public facilities were 4.9 times less likely than those who visited non-public facilities to emphasise the influence of cost in accessing and utilising health care (OR = 4.9, CI 3.9-6.1). A significant difference was also found in the provider-client relationship satisfaction level between non-public (89.1%) and public facilities (74.7%) (OR = 2.8, CI: 1.5-5.0), indicating a level of lower trust in the later. Revised strategies are needed to ensure availability of medicines in public facilities, which are used by the majority of the population, while strengthening private-public partnerships to harmonise healthcare costs. PMID- 26883024 TI - Comorbid Gender Dysphoria in a Preadolescent Boy With Fragile X Syndrome. PMID- 26883022 TI - Selective adsorption and efficient regeneration via smart adsorbents possessing thermo-controlled molecular switches. AB - Adsorption and desorption are equally important in an adsorptive separation process, while conventional adsorbents with fixed pores benefit only one of them rather than both. Here, a new generation of adsorbents was fabricated by incorporating thermo-responsive polymers (TRPs) into pores. The TRPs act as molecular switches, making pore spaces and active sites responsive to adsorption/desorption conditions. The adsorbents can thus realize both selective adsorption and efficient desorption, which are extremely desirable for adsorptive separation. PMID- 26883025 TI - Measuring Gender Dysphoria: A Multicenter Examination and Comparison of the Utrecht Gender Dysphoria Scale and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults. AB - This study examined two instruments measuring gender dysphoria within the multicenter study of the European Network for the Investigation of Gender Incongruence (ENIGI). The Utrecht Gender Dysphoria Scale (UGDS) and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA) were examined for their definitions of gender dysphoria and their psychometric properties, and evaluated for their congruence in assessing the construct. The sample of 318 participants consisted of 178 male-to-females (MtF) and 140 female to-males (FtM) who were recruited from the four ENIGI gender clinics. Both instruments were significantly correlated in the group of MtFs. For the FtM group, there was a trend in the same direction but smaller. Gender dysphoria was found to be defined differently in the two instruments, which led to slightly different findings regarding the subgroups. The UGDS detected a difference between the subgroups of early and late onset of gender identity disorder in the group of MtFs, whereas the GIDYQ-AA did not. For the FtM group, no significant effect of age of onset was found. Therefore, both instruments seem to capture not only similar but also different aspects of gender dysphoria. The UGDS focusses on bodily aspects, gender identity, and gender role, while the GIDYQ-AA addresses subjective, somatic, social, and sociolegal aspects. For future research, consistency in theory and definition of gender dysphoria is needed and should be in line with the DSM-5 diagnosis of gender dysphoria in adolescents and adults. PMID- 26883026 TI - On the Association Between Self-Reported Own- and Other-Gender Similarity and the Use of Physical and Relational Aggression in Sixth Grade Children. AB - The goal was to assess the association between felt similarity to each gender (an aspect of gender identity) and girls' and boys' differential use of relational versus physical aggression. We extend past research on gender differences in the use of aggression by expanding the gender dichotomy and allowing for more variations in an individual's gender identity. Students (N = 414, 47 % female, 6th grade) reported how similar they felt to both their own- and other-gender peers, from which cluster analyses derived four typologies of perceived gender similarity (those who feel similar to their own-gender group; those who feel similar to the other-gender group; those who feel similar to both gender groups; those who feel similar to neither gender group). Peers reported which classmates were relationally and physically aggressive. Analyses compared how girls and boys in each typology of gender similarity differed in their use of relational and physical aggression. Results indicated that most children were engaged in gender normative aggression more than gender non-normative aggression (with the notable exception of low-gender similar girls). Findings were discussed in terms of their importance both for examining a broad spectrum of gender similarity and for understanding the use of aggressive behavior among children. PMID- 26883027 TI - Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma. AB - Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores >=2. Three-year event free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes. PMID- 26883028 TI - Immunization of A4galt-deficient mice with glycosphingolipids from renal cell cancers resulted in the generation of anti-sulfoglycolipid monoclonal antibodies. AB - In this study, we immunized Gb3/CD77 synthase gene (A4galt) knockout (KO) mice with glycosphingolipids (GSLs) extracted from 3 renal cell cancer (RCC) cell lines to raise monoclonal antibodies (mAbs) reactive with globo-series GSLs specifically expressed in RCCs. Although a number of mAbs reactive with globo series GSLs were generated, they reacted with both RCC cell lines and normal kidney cells. When we analyzed recognized antigens by mAbs that were specifically reactive with RCC, but not with normal kidney cells at least on the cell surface, many of them turned out to be reactive with sulfoglycolipids. Eight out of 11 RCC specific mAbs were reactive with SM2 alone, and the other 3 mAbs were more broadly reactive with sulfated glycolipids, i.e. SM3 and SM4 as well as SM2. In the immunohistochemistry, these anti-sulfoglycolipids mAbs showed RCC-specific reaction, with no or minimal reaction with adjacent normal tissues. Thus, immunization of A4galt KO mice with RCC-derived GSLs resulted in the generation of anti sulfated GSL mAbs, and these mAbs may be applicable for the therapeutics for RCC patients. PMID- 26883030 TI - Social Movements Against Racist Police Brutality and Department of Justice Intervention in Prince George's County, Maryland. AB - Racist police brutality has been systemic in Prince George's County, Maryland. The victims include African Americans, the mentally challenged, and immigrant populations, creating a complex and uneven public health impact. Three threads characterize the social movements and intervention since 1970. First, a significant demographic shift occurred as African Americans became the majority population in the late 1980s when the first Black county executive was elected in 1994. Despite the change in political leadership, police brutality remained rampant. Lower-income households located close to the District of Columbia and "inside the beltway" experienced the most police brutality. In 2001, The Washington Post revealed that between 1990 and 2000, Prince George's police shot and killed more citizens per officer than any of the 50 largest city and county law enforcement agencies in the country, 84 % of whom were black. Of the 147 persons shot during the 1990s, 12 were mentally and/or emotionally disturbed; 6 of these shootings were fatal. Second, resistance to police brutality emerged in a variety of political formations throughout the period, especially in the late 1990s. Sustained community pressure prompted the Department of Justice (DOJ) to open a civil rights investigation of the police department in November 2000. To avoid a potential federal lawsuit, the county leadership negotiated a memorandum of agreement (MOA) with the DOJ to enact policy reforms, part of which called for supplementing the departmental mobile crisis team, comprised of mental health care professionals, to respond to all cases involving mentally challenged citizens. Third, the incomplete process of change subsequent to the ending of DOJ oversight suggests a continued challenge to social movements opposing police brutality. This study focuses on the effectiveness of the MOA along with the activism of the People's Coalition for Police Accountability (PCPA) in reforming a culture of police brutality. The intensive oversight by the DOJ, combined with engaged resident activism, reduced the incidences of police brutality during the period 2004-2013. Since the termination of DOJ oversight, disturbing developments suggest the need for continued and sustained activism. Since 2010, county police officers have fatally shot 21 people, several in questionable circumstances. At the same time, the Prince George's Police Department has received more tactical military weaponry than any other jurisdiction in the state of Maryland under the 1033 program of the National Defense Authorization Act. PMID- 26883029 TI - Postpartum Pain in the Community Among Migrant and Non-migrant Women in Canada. AB - International migrant women of childbearing age represent a large proportion of immigrants to high-income countries, yet research focusing on their postpartum health is limited. We investigated predictive factors for breast and non-breast pain 1 week post-birth in migrant and non-migrant women in Canada. Among migrant women, difficulty accessing health services; being from a middle-or high-income country; poor functionality in English and French; living with the father of their infant; and having no regular care provider were predictive of breast pain. Among non-migrant women, difficulties accessing health services, multiparity and prenatal education were predictive of breast pain, while receiving an epidural and having no regular care provider were predictive of non-breast pain. Among both groups, difficulties accessing health services and having no regular care provider were predictive of breast pain, while second degree or higher perineal tearing was predictive of non-breast pain. Migration-specific indicators should be considered in postpartum care planning. PMID- 26883031 TI - TransMilenio, a Scalable Bus Rapid Transit System for Promoting Physical Activity. AB - Transport systems can play an important role in increasing physical activity (PA). Bogota has been recognized for its bus rapid transit (BRT) system, TransMilenio (TM). To date, BRTs have been implemented in over 160 cities worldwide. The aim of this study was to assess the association between PA and the use of TM among adults in Bogota. The study consists of a cross-sectional study conducted from 2010 to 2011 with 1000 adults. PA was measured using the International Physical Activity Questionnaire. In a subsample of 250 adults, PA was objectively measured using ActiGraph accelerometers. Analyses were conducted using multilevel logistic regression models. The use of TM was associated with meeting moderate-to-vigorous PA (MVPA). TM users were more likely to complete an average of >22 min a day of MVPA (odds ratio [OR] = 3.1, confidence interval [CI] = 95 % 1.4-7.1) and to walk for transportation for >=150 min per week (OR = 1.5; CI = 95 % 1.1-2.0). The use of TM was associated with 12 or more minutes of MVPA (95 % CI 4.5-19.4, p < 0.0001). Associations between meeting PA recommendations and use of TM did not differ by socioeconomic status (p value = 0.106) or sex (p value = 0.288). The use of TM is a promising strategy for enhancing public health efforts to reduce physical inactivity through walking for transport. Given the expansion of BRTs, these results could inform the development of transport PA programs in low- to high-income countries. PMID- 26883032 TI - Distribution and Fate of Mercury in Pulverized Bituminous Coal-Fired Power Plants in Coal Energy-Dominant Huainan City, China. AB - A better understanding on the partitioning behavior of mercury (Hg) during coal combustion in large-scale coal-fired power plants is fundamental for drafting Hg emission control regulations. Two large coal-fired utility boilers, equipped with electrostatic precipitators (ESPs) and a wet flue gas desulfurization (WFGD) system, respectively, in coal energy-dominant Huainan City, China, were selected to investigate the distribution and fate of Hg during coal combustion. In three sampling campaigns, we found that Hg in bottom ash was severely depleted with a relative enrichment (RE) index <7 %, whereas the RE index for fly ash (9-54%) was comparatively higher and variable. Extremely high Hg was concentrated in gypsum (<=4500 ng/g), which is produced in the WFGD system. Mass balance calculation shows that the shares of Hg in bottom ash, fly ash, WFGD products (gypsum, effluents, sludge), and stack emissions were <2, 17-32, 7-22, and 54-82%, respectively. The Hg-removal efficiencies of ESPs, WFGD, and ESPs + WFGD were 17 32, 10-29, and 36-46%, respectively. The Hg-emission factor of studied boilers was in a high range of 0.24-0.29 g Hg/t coal. We estimated that Hg emissions in all Huainan coal-fired power plants varied from 1.8 Mg in 2003 to 7.3 Mg in 2010. PMID- 26883034 TI - Differential effects of a high-fat diet on serum lipid parameters and ovarian gene expression in young and aged female mice. AB - The aim of this study was to compare serum lipid profiles and ovarian gene expression between aged and younger female mice fed a control or a high-fat diet for 2 months. For this 16 female mice (C57BL/6) of 4 months (Young, n = 8) or 13 months (Old, n = 8) of age were used. The females were divided into four groups: (i) young females fed a normal diet; (ii) young females fed a high-fat diet; (iii) old females fed a normal diet; and (iv) old females fed a high-fat diet. Food intake was reduced (P < 0.05) in mice fed with a high-fat (2.9 +/- 0.1 g) diet in comparison with control mice (3.9 +/- 0.1 g). Body weight was higher for old females on the high-fat diet (35.1 +/- 0.3 g) than for young females on the same diet (23.3 +/- 0.4 g; P < 0.05). PON1 activity was lower in the high-fat than control diet group (114.3 +/- 5.8 vs. 78.1 +/- 6.0 kU/L, respectively) and was higher in older than younger females (85.9 +/- 6.4 vs. 106.5 +/- 5.3; P < 0.05, respectively). Females fed a high-fat diet had lower expression of Igf1 mRNA (P = 0.04). There was an interaction between age and diet for the expression of Gdf9 and Survivin, with lower expression in older females in both diets and young females that received the high-fat diet (P < 0.05). Concluding, the high fat diet reduced the expression of ovarian Igf1 mRNA, and Gdf9 and Survivin mRNA in younger females, which can indicate lower fertility rates. High-density lipoprotein concentration and PON1 activity were higher in aged female mice. PMID- 26883037 TI - The EPA guidance document series. PMID- 26883033 TI - EOS((r)) biplanar X-ray imaging: concept, developments, benefits, and limitations. AB - PURPOSE: In 1992, Georges Charpak invented a new type of X-ray detector, which in turn led to the development of the EOS((r)) 2D/3D imaging system. This system takes simultaneous anteroposterior and lateral 2D images of the whole body and can be utilized to perform 3D reconstruction based on statistical models. The purpose of this review is to present the state of the art for this EOS((r)) imaging technique, to report recent developments and advances in the technique, and to stress its benefits while also noting its limitations. METHODS: The review was based on a thorough literature search on the subject as well as personal experience gained from many years of using the EOS((r)) system. RESULTS: While EOS((r)) imaging could be proposed for many applications, it is most useful in relation to scoliosis and sagittal balance, due to its ability to take simultaneous orthogonal images while the patient is standing, to perform 3D reconstruction, and to determine various relationships among adjacent segments (cervical spine, pelvis, and lower limbs). The technique has also been validated for the study of pelvic and lower-limb deformity and pathology in adult and pediatric populations; in such a study it has the advantage of allowing the measurement of torsional deformity, which classically requires a CT scan. CONCLUSIONS: The major advantages of EOS((r)) are the relatively low dose of radiation (50-80 % less than conventional X-rays) that the patient receives and the possibility of obtaining a 3D reconstruction of the bones. However, this 3D reconstruction is not created automatically; a well-trained operator is required to generate it. The EOS((r)) imaging technique has proven itself to be a very useful research and diagnostic tool. PMID- 26883035 TI - Investigation of a High-Dose pH-Dependent-Release Mesalazine on the Induction of Remission in Active Crohn's Disease. AB - INTRODUCTION: The effect of mesalazine in treating active Crohn's disease (CD) remains controversial, possibly due to the various formulae of mesalazine used to treat inflammation located in different regions of the digestive tract. METHODS: This exploratory, multicenter, uncontrolled, open-label study included 17 patients with active CD. The inclusion criteria were patients with a CD activity index (CDAI) of >= 200 and <350, and in whom mucosal lesions were observed in the area from the terminal ileum to the rectum using colonoscopy (CS). Each patient was treated with pH-dependent-release mesalazine at 4.8 g/day. The drug was administered three times daily for 12 weeks. Efficacy was evaluated by the change in CDAI at the time of final observation (at week 12 or at discontinuation), and safety was evaluated by the incidence of adverse events (AEs) and adverse drug reactions (ADRs). RESULTS: In the full analysis set (n = 17), the change in CDAI at the time of final observation was -67.4, and the mean change in CDAI from baseline was -49.3 at week 2, -61.8 at week 4, -78.3 at week 8, and -101.1 at week 12. A statistically significant improvement was observed from week 2 to week 12 compared with baseline, and the incidences of AEs and ADRs were 94.1 and 58.8%, respectively. All events were known events, as the results suggested, which is in line with the known safety profile of pH-dependent-release mesalazine. CONCLUSIONS: The results suggest that the administration of pH dependent-release mesalazine 4.8 g/day for 12 weeks could be an effective and highly safe treatment option for patients with mild to moderately active CD in whom mucosal lesions were observed in the area from the terminal ileum to the rectum. TRIAL REGISTRATION NUMBER: JapicCTI-111460. PMID- 26883036 TI - High-grade hemorrhoids requiring surgical treatment are common after laparoscopic ventral mesh rectopexy. AB - PURPOSE: To describe patients developing grade III and IV hemorrhoids requiring surgery after laparoscopic ventral mesh rectopexy (LVMR) and to explore the relationship between developing such hemorrhoids and recurrence of rectal prolapse after LVMR. METHODS: All consecutive patients receiving LVMR at the Meander Medical Centre, Amersfoort, the Netherlands, between 2004 and 2013 were analyzed. Kaplan-Meier estimates were calculated for recurrences. RESULTS: A total of 420 patients underwent LVMR. Sixty-five of these patients (actuarial 5 year incidence 24.3, 95 % confidence interval (CI) 18.6-30.0) developed symptomatic grade III/IV hemorrhoids requiring stapled or excisional hemorrhoidectomy. Re-do surgery for recurrent grade III/IV hemorrhoids was required for 15 of the 65 patients (actuarial 5-year recurrence rate 40.6, 95 % CI 23.2-58.0) after the primary hemorrhoidectomy. Three of the 65 patients developed an external rectal prolapse (ERP) recurrence and eight an internal rectal prolapse (IRP) recurrence. This generated a 5-year recurrence rate of 25.3 % (95 % CI 0-53.9) for ERP recurrence and 24.4 % (95 % CI 9.1-39.7) for IRP recurrence. The rest of the LVMR cohort not receiving additional surgery for hemorrhoids (n = 355) showed significantly lower actuarial 5-year ERP (0.8 %, p = 0.011) and IRP (11 %, p = 0.020) recurrence rates. CONCLUSION: High-grade hemorrhoids requiring surgery may be common after LVMR. The development of high grade hemorrhoids after LVMR might be considered a predictor of rectal prolapse recurrence. PMID- 26883038 TI - Coupled electrophysiological recording and single cell transcriptome analyses revealed molecular mechanisms underlying neuronal maturation. AB - The mammalian brain is heterogeneous, containing billions of neurons and trillions of synapses forming various neural circuitries, through which sense, movement, thought, and emotion arise. The cellular heterogeneity of the brain has made it difficult to study the molecular logic of neural circuitry wiring, pruning, activation, and plasticity, until recently, transcriptome analyses with single cell resolution makes decoding of gene regulatory networks underlying aforementioned circuitry properties possible. Here we report success in performing both electrophysiological and whole-genome transcriptome analyses on single human neurons in culture. Using Weighted Gene Coexpression Network Analyses (WGCNA), we identified gene clusters highly correlated with neuronal maturation judged by electrophysiological characteristics. A tight link between neuronal maturation and genes involved in ubiquitination and mitochondrial function was revealed. Moreover, we identified a list of candidate genes, which could potentially serve as biomarkers for neuronal maturation. Coupled electrophysiological recording and single cell transcriptome analysis will serve as powerful tools in the future to unveil molecular logics for neural circuitry functions. PMID- 26883039 TI - Targeted genotyping-by-sequencing permits cost-effective identification and discrimination of pasture grass species and cultivars. AB - KEY MESSAGE: A targeted amplicon-based genotyping-by-sequencing approach has permitted cost-effective and accurate discrimination between ryegrass species (perennial, Italian and inter-species hybrid), and identification of cultivars based on bulked samples. Perennial ryegrass and Italian ryegrass are the most important temperate forage species for global agriculture, and are represented in the commercial pasture seed market by numerous cultivars each composed of multiple highly heterozygous individuals. Previous studies have identified difficulties in the use of morphophysiological criteria to discriminate between these two closely related taxa. Recently, a highly multiplexed single nucleotide polymorphism (SNP)-based genotyping assay has been developed that permits accurate differentiation between both species and cultivars of ryegrasses at the genetic level. This assay has since been further developed into an amplicon-based genotyping-by-sequencing (GBS) approach implemented on a second-generation sequencing platform, allowing accelerated throughput and ca. sixfold reduction in cost. Using the GBS approach, 63 cultivars of perennial, Italian and interspecific hybrid ryegrasses, as well as intergeneric Festulolium hybrids, were genotyped. The genetic relationships between cultivars were interpreted in terms of known breeding histories and indistinct species boundaries within the Lolium genus, as well as suitability of current cultivar registration methodologies. An example of applicability to quality assurance and control (QA/QC) of seed purity is also described. Rapid, low-cost genotypic assays provide new opportunities for breeders to more fully explore genetic diversity within breeding programs, allowing the combination of novel unique genetic backgrounds. Such tools also offer the potential to more accurately define cultivar identities, allowing protection of varieties in the commercial market and supporting processes of cultivar accreditation and quality assurance. PMID- 26883040 TI - Production and cytomolecular identification of new wheat-perennial rye (Secale cereanum) disomic addition lines with yellow rust resistance (6R) and increased arabinoxylan and protein content (1R, 4R, 6R). AB - KEY MESSAGE: Wheat-Secale cereanum addition lines with yellow rust resistance (6R) and increased arabinoxylan content (1R, 4R, 6R) have been selected and identified in order to increase biodiversity of wheat. Perennial rye (Secale cereanum, 2n = 2x = 14, RR) cultivar Kriszta has a large gene pool that can be exploited in wheat breeding. It has high protein and dietary fibre content, carries several resistance genes, tolerant to frost and drought, and adapts well to disadvantageous soil and weather conditions. In order to incorporate agronomically useful features from this perennial rye into cultivated wheat, backcross progenies derived from a cross between the wheat line Mv9kr1 and perennial rye 'Kriszta' have been produced, and addition lines disomic for 1R, 4R and 6R chromosomes have been selected using GISH, FISH and SSR markers. Quality measurements showed that addition of 'Kriszta' chromosomes 4R and 6R to the wheat genome had increased the total protein content. The 4R addition line contained slightly, while 1R and 6R additions significantly higher amount of arabinoxylan than the parental wheat line. Besides this, the 6R addition line appeared to be resistant to yellow rust in highly infected nurseries, consequently it may carry a new effective gene different from that harboured in the 1RS.1BL translocation for resistance to this disease. PMID- 26883041 TI - Integrated analysis in bi-parental and natural populations reveals CsCLAVATA3 (CsCLV3) underlying carpel number variations in cucumber. AB - KEY MESSAGE: Carpel number variation in cucumber was controlled by a single gene, Cn . Linkage and association analysis revealed CsCLV3 as the candidate gene of the Cn locus. Carpel number (CN) is an important fruit quality trait of cucumber, but the genetic basis of CN variations is largely unknown. In the present study, segregating analysis in multiple bi-parental mapping populations (F2, F3, and RILs) derived from WI2757 (CN = 3) * True Lemon (CN = 5) suggested that CN is controlled by a simply inherited gene, Cn, with CN = 3 being incompletely dominant to CN = 5. Initial linkage mapping located Cn in a 1.9-Mb region of cucumber chromosome 1. Exploration of DNA sequence variations in this region with in silico bulked segregant analysis among eight re-sequenced lines allowed delimiting the Cn locus to a 16-kb region with five predicted genes including CsCLV3, a homolog of the Arabidopsis gene CLAVATA3. Fine genetic mapping in F2 and RIL populations and association analysis in natural populations confirmed CsCLV3 as the candidate gene for Cn, which was further evidenced from gene expression analysis and microscopic examination of floral meristem size in the two parent lines. This study highlights the importance of integrated use of linkage and association analysis as well as next-gen high-throughput sequencing in mapping and cloning genes that are difficult in accurate genotyping. The results provide new insights into the genetic control of CN variations in cucumber, which were discussed in the context of the well-characterized CLAVATA pathway for stem cell homeostasis and regulation of meristem sizes in plants. The associations of carpel number with fruit shape, size, and weight in cucumber and melon are also discussed. PMID- 26883042 TI - Genetic mapping and molecular marker development for Pi65(t), a novel broad spectrum resistance gene to rice blast using next-generation sequencing. AB - KEY MESSAGE: A novel R gene was mapped to a locus on chromosome 11 from 30.42 to 30.85 Mb, which was proven to be efficient in the improvement of rice blast resistance. Rice blast is a devastating fungal disease worldwide. The use of blast resistance (R) genes is the most important approach to control the disease in rice breeding. In the present study, we finely mapped a novel resistance gene Pi65(t), conferring a broad-spectrum resistance to the fungus Magnaporthe oryzae, using bulked segregant analysis in combination with next-generation sequencing technology. Segregation in a doubled haploid (DH) population and a BC1F2 population suggested that resistance to blast in Gangyu129 was likely conferred by a single dominant gene, designated Pi65(t); it was located on chromosome 11 from 30.20 to 31.20 Mb using next-generation sequencing. After screening recombinants with newly developed molecular markers, the region was narrowed down to 0.43 Mb, flanked by SNP-2 and SNP-8 at the physical location from 30.42 to 30.85 Mb based on the Nipponbare reference database in build 5. Using the software QTL IciMapping, Pi65(t) was further mapped to a locus between InDel-1 and SNP-4 with genetic distances of 0.11 and 0.98 cM, respectively. Within this region, 4 predicted R genes were found with nucleotide binding site and leucine rich repeat (NBS-LRR) domains. We developed molecular markers to genotype 305 DH lines and found that InDel-1 was closely linked with Pi65(t). Using InDel-1, a new rice variety Chuangxin1 containing Pi65(t) was developed, and it is highly resistant to rice blast and produces a high yield in Liaoning province of China. This indicated that Pi65(t) could play a key role in the improvement of rice blast resistance. PMID- 26883043 TI - Mapping by sequencing in cotton (Gossypium hirsutum) line MD52ne identified candidate genes for fiber strength and its related quality attributes. AB - KEY MESSAGE: Three QTL regions controlling three fiber quality traits were validated and further fine-mapped with 27 new single nucleotide polymorphism (SNP) markers. Transcriptome analysis suggests that receptor-like kinases found within the validated QTLs are potential candidate genes responsible for superior fiber strength in cotton line MD52ne. Fiber strength, length, maturity and fineness determine the market value of cotton fibers and the quality of spun yarn. Cotton fiber strength has been recognized as a critical quality attribute in the modern textile industry. Fine mapping along with quantitative trait loci (QTL) validation and candidate gene prediction can uncover the genetic and molecular basis of fiber quality traits. Four previously-identified QTLs (qFBS c3, qSFI-c14, qUHML-c14 and qUHML-c24) related to fiber bundle strength, short fiber index and fiber length, respectively, were validated using an F3 population that originated from a cross of MD90ne * MD52ne. A group of 27 new SNP markers generated from mapping-by-sequencing (MBS) were placed in QTL regions to improve and validate earlier maps. Our refined QTL regions spanned 4.4, 1.8 and 3.7 Mb of physical distance in the Gossypium raimondii reference genome. We performed RNA sequencing (RNA-seq) of 15 and 20 days post-anthesis fiber cells from MD52ne and MD90ne and aligned reads to the G. raimondii genome. The QTL regions contained 21 significantly differentially expressed genes (DEGs) between the two near-isogenic parental lines. SNPs that result in non-synonymous substitutions to amino acid sequences of annotated genes were identified within these DEGs, and mapped. Taken together, transcriptome and amino acid mutation analysis indicate that receptor like kinase pathway genes are likely candidates for superior fiber strength and length in MD52ne. MBS along with RNA-seq demonstrated a powerful strategy to elucidate candidate genes for the QTLs that control complex traits in a complex genome like tetraploid upland cotton. PMID- 26883044 TI - Outlier detection methods for generalized lattices: a case study on the transition from ANOVA to REML. AB - KEY MESSAGE: We review and propose several methods for identifying possible outliers and evaluate their properties. The methods are applied to a genomic prediction program in hybrid rye. Many plant breeders use ANOVA-based software for routine analysis of field trials. These programs may offer specific in-built options for residual analysis that are lacking in current REML software. With the advance of molecular technologies, there is a need to switch to REML-based approaches, but without losing the good features of outlier detection methods that have proven useful in the past. Our aims were to compare the variance component estimates between ANOVA and REML approaches, to scrutinize the outlier detection method of the ANOVA-based package PlabStat and to propose and evaluate alternative procedures for outlier detection. We compared the outputs produced using ANOVA and REML approaches of four published datasets of generalized lattice designs. Five outlier detection methods are explained step by step. Their performance was evaluated by measuring the true positive rate and the false positive rate in a dataset with artificial outliers simulated in several scenarios. An implementation of genomic prediction using an empirical rye multi environment trial was used to assess the outlier detection methods with respect to the predictive abilities of a mixed model for each method. We provide a detailed explanation of how the PlabStat outlier detection methodology can be translated to REML-based software together with the evaluation of alternative methods to identify outliers. The method combining the Bonferroni-Holm test to judge each residual and the residual standardization strategy of PlabStat exhibited good ability to detect outliers in small and large datasets and under a genomic prediction application. We recommend the use of outlier detection methods as a decision support in the routine data analyses of plant breeding experiments. PMID- 26883045 TI - A splice acceptor site mutation in TaGW2-A1 increases thousand grain weight in tetraploid and hexaploid wheat through wider and longer grains. AB - KEY MESSAGE: Across 13 experiments the gw2 - A1 mutant allele shifts grain size distribution consistently across all grains significantly increasing grain weight (6.6 %), width (2.8 %) and length (2.1 %) in tetraploid and hexaploid wheat. There is an urgent need to identify, understand and incorporate alleles that benefit yield in polyploid wheat. The rice OsGW2 gene functions as a negative regulator of grain weight and width and is homologous to the wheat TaGW2 gene. Previously it was shown that transcript levels of the A-genome homoeologue, TaGW2 A1, are negatively associated with grain width in hexaploid wheat. In this study we screened the tetraploid Kronos TILLING population to identify mutants in TaGW2 A1. We identified a G to A transition in the splice acceptor site of exon 5 which leads to mis-splicing in TaGW2-A1. We backcrossed the mutant allele into tetraploid and hexaploid wheat and generated a series of backcross derived isogenic lines which were evaluated in glasshouse and field conditions. Across 13 experiments the GW2-A1 mutant allele significantly increased thousand grain weight (6.6 %), grain width (2.8 %) and grain length (2.1 %) in tetraploid and hexaploid wheat compared to the wild type allele. In hexaploid wheat, this led to an increase in spike yield since no differences were detected for spikelet or grain number between isogenic lines. The increase in grain width and length was consistent across grains of different sizes, suggesting that the effect of the mutation is stable across the ear and within spikelets. Differences in carpel size and weight between alleles were identified as early as 5 days before anthesis, suggesting that TaGW2-A1 acts on maternal tissue before anthesis to restrict seed size. A single nucleotide polymorphism marker was developed to aid the deployment of the mutant allele into breeding programmes. PMID- 26883046 TI - Copy number variation of CBF-A14 at the Fr-A2 locus determines frost tolerance in winter durum wheat. AB - KEY MESSAGE: Frost tolerance in durum wheat is mainly controlled by copy number variation of CBF - A14 at the Fr - A2 locus. Frost tolerance is a key trait for successful breeding of winter durum wheat (Triticum durum) which can increase the yield performance in regions favoring autumn-sown winter cereals. The aim of this study was to investigate the genetic architecture of frost tolerance in order to provide molecular support for the breeding of winter durum wheat. To this end, a diverse panel of 170 winter and 14 spring durum wheat genotypes of worldwide origin was evaluated for frost tolerance in the field, as well as in a semi controlled test. A total of 30,611 polymorphic genome-wide markers obtained by a genotyping-by-sequencing approach and markers for candidate loci were used to assess marker-trait associations. One major QTL was detected on chromosome 5A, likely corresponding to Frost Resistance-A2 (Fr-A2). Further analyses strongly support the conclusion that copy number variation of CBF-A14 at the Fr-A2 locus is the causal polymorphism underlying this major QTL. It explains 91.6 % of the genotypic variance and a haploblock of two strongly associated markers in the QTL region also allowed to capture the variance of this QTL. In addition to this major QTL, a much smaller contribution of 4.2 % was observed for Fr-B2. We further investigated this major QTL and found that the copy number of CBF-A14 and the frequency of the frost tolerant haplotype mirrored the climatic conditions in the genotypes' country of origin, suggesting selection through breeding. Two functional KASP markers were developed which facilitate a high-throughput screening of the haploblock and thus a marker-based breeding of frost tolerance in winter durum wheat. PMID- 26883047 TI - Cloning of TaSST genes associated with water soluble carbohydrate content in bread wheat stems and development of a functional marker. AB - KEY MESSAGE: We cloned TaSST genes, developed a gene-specific marker for TaSST D1, and identified three QTL in the Doumai/Shi 4185 RIL population. TaSST-D1 is within one of the three QTL. Sucrose:sucrose-1-fructosyltransferase (1-SST), a critical enzyme in the fructan biosynthetic pathway, is significantly and positively associated with water soluble carbohydrate (WSC) content in bread wheat stems. In the present study, wheat 1-SST genes (TaSST) were isolated and located on chromosomes 4A, 7A and 7D. Sequence analysis of TaSST-D1 revealed 15 single nucleotide polymorphisms (SNP) in the third exon between cultivars with higher and lower WSC content. A cleaved amplified polymorphism sequence (CAPS) marker, WSC7D, based on the polymorphism at position 1216 (C-G) was developed to discriminate the two alleles. WSC7D was located on chromosome 7DS using a recombinant inbred line (RIL) population from a Doumai/Shi 4185 cross, and a set of Chinese Spring nullisomic-tetrasomic lines. TaSST-D1 co-segregated with the CAPS marker WSC7D and was linked to SNP marker BS00108793_51 on chromosome 7DS at a genetic distance of 6.1 cM. It explained 8.8, 10.9, and 11.3% of the phenotypic variances in trials at Beijing and Shijiazhuang as well as the averaged data from those environments, respectively. Two additional QTL (QWSC.caas-4BS and QWSC.caas 7AS) besides TaSST-D1 were mapped in the RIL population. One hundred and forty nine Chinese wheat cultivars and advanced lines tested in four environments were used to validate a highly significant (P < 0.01) association between WSC7D and WSC content in wheat stems. WSC7D can be used as a gene-specific marker for improvement of stem WSC content in wheat breeding programs. PMID- 26883048 TI - Epistasis and covariance: how gene interaction translates into genomic relationship. AB - KEY MESSAGE: Models based on additive marker effects and on epistatic interactions can be translated into genomic relationship models. This equivalence allows to perform predictions based on complex gene interaction models and reduces computational effort significantly. In the theory of genome-assisted prediction, the equivalence of a linear model based on independent and identically normally distributed marker effects and a model based on multivariate Gaussian distributed breeding values with genomic relationship as covariance matrix is well known. In this work, we demonstrate equivalences of marker effect models incorporating epistatic interactions and corresponding mixed models based on relationship matrices and show how to exploit these equivalences computationally for genome-assisted prediction. In particular, we show how models with epistatic interactions of higher order (e.g., three-factor interactions) translate into linear models with certain covariance matrices and demonstrate how to construct epistatic relationship matrices for the linear mixed model, if we restrict the model to interactions defined a priori. We illustrate the practical relevance of our results with a publicly available data set on grain yield of wheat lines growing in four different environments. For this purpose, we select important interactions in one environment and use this knowledge on the network of interactions to increase predictive ability of grain yield under other environmental conditions. Our results provide a guide for building relationship matrices based on knowledge on the structure of trait-related gene networks. PMID- 26883050 TI - Relationships between suicidal ideation and psychosocial factors among residents living in Nagano Prefecture of Japan. AB - OBJECTIVES: Feeling ashamed for seeking help when distressed is known to be a critical factor promoting suicidal behaviors. The objective of this study was to examine the relationship between suicidal ideation and psychosocial factors, including worries or anxieties, having a person to confide in, feeling ashamed for seeking help when distressed, and K6 score. METHODS: Fourteen out of 77 municipalities from Nagano Prefecture participated in this questionnaire survey. Participants of both sexes over 20 years of age were randomly selected according to age distribution in each municipality. Association between suicidal ideation and sociodemographic and psychosocial factors, including "feeling ashamed for seeking help", were determined by multiple logistic regression analysis. RESULTS: Among a total of 11,100 participants, 7394 (66.6%) returned the questionnaire. 2147 participants responded properly to essential study parameters and were submitted to the final analyses. The adjusted odds ratio of suicidal ideation was 2.09 (95% CI 1.49-2.94) among participants feeling ashamed for seeking help, compared to those not feeling ashamed. Although the rate of "no person to confide in" was 4.4%, participants who responded with "no person to confide in" had significantly increased odds ratio of suicidal ideation compared with those who responded with "having a person to confide in" (OR 1.97, 95% CI 1.12-3.47). CONCLUSIONS: Our findings suggest a need for tailored intervention targeting individuals at risk by gatekeepers to encourage individuals at risk to overcome feeling ashamed for seeking help and to cultivate an appropriate person to confide in. PMID- 26883049 TI - Reliability and validity of Japanese versions of KIDSCREEN-27 and KIDSCREEN-10 questionnaires. AB - OBJECTIVE: This study aimed to assess the reliability and validity of Japanese versions of the KIDSCREEN-27 (J-KIDSCREEN-27) and KIDSCREEN-10 (J-KIDSCREEN-10) questionnaires, which are shorter versions of the KIDSCREEN-52 (J-KIDSCREEN-52). METHODS: The present analyses are based on a pre-existing dataset of the J KIDSCREEN-52 validation study, including 1564 children and adolescents aged 8-18 years and their 1326 parents. All were asked to complete the J-KIDSCREEN and Pediatric Quality of Life Inventory (PedsQL) questionnaires. Test-retest reliability was assessed with Intraclass Correlation Coefficients (ICCs) in a one way random effects model, and internal consistency reliability was measured using Cronbach's alpha coefficients. Agreement between child and parent scores was evaluated using ICCs in a two-way mixed effects model. To assess concurrent validity, a sub-sample of 535 parents evaluated their child's mental health status using the Strengths and Difficulties Questionnaire (SDQ). RESULTS: For children, test-retest ICCs were >=0.60 and Cronbach's alpha >=0.70 for every dimension of both instruments. Correlations of corresponding dimensions between the J-KIDSCREEN-27 or -10 and the PedsQL were acceptable. For parents, test retest ICCs were >=0.60, Cronbach's alpha >=0.70, and ICCs between child and parent scores >=0.41 in every dimension of both instruments. In multivariate logistic regression models, after adjusting for confounders, lower health-related QOL in every dimension of both instruments, except Physical Well-being, was significantly associated with higher odds ratios for borderline and clinical ranges of the SDQ. CONCLUSION: The child/adolescent and parent/proxy versions of the J-KIDSCREEN-27 and J-KIDSCREEN-10 demonstrated acceptable levels of reliability and validity. PMID- 26883051 TI - Deep RNA-Seq profile reveals biodiversity, plant-microbe interactions and a large family of NBS-LRR resistance genes in walnut (Juglans regia) tissues. AB - Deep RNA-Seq profiling, a revolutionary method used for quantifying transcriptional levels, often includes non-specific transcripts from other co existing organisms in spite of stringent protocols. Using the recently published walnut genome sequence as a filter, we present a broad analysis of the RNA-Seq derived transcriptome profiles obtained from twenty different tissues to extract the biodiversity and possible plant-microbe interactions in the walnut ecosystem in California. Since the residual nature of the transcripts being analyzed does not provide sufficient information to identify the exact strain, inferences made are constrained to the genus level. The presence of the pathogenic oomycete Phytophthora was detected in the root through the presence of a glyceraldehyde-3 phosphate dehydrogenase. Cryptococcus, the causal agent of cryptococcosis, was found in the catkins and vegetative buds, corroborating previous work indicating that the plant surface supported the sexual cycle of this human pathogen. The RNA Seq profile revealed several species of the endophytic nitrogen fixing Actinobacteria. Another bacterial species implicated in aerobic biodegradation of methyl tert-butyl ether (Methylibium petroleiphilum) is also found in the root. RNA encoding proteins from the pea aphid were found in the leaves and vegetative buds, while a serine protease from mosquito with significant homology to a female reproductive tract protease from Drosophila mojavensis in the vegetative bud suggests egg-laying activities. The comprehensive analysis of RNA-seq data present also unraveled detailed, tissue-specific information of ~400 transcripts encoded by the largest family of resistance (R) genes (NBS-LRR), which possibly rationalizes the resistance of the specific walnut plant to the pathogens detected. Thus, we elucidate the biodiversity and possible plant-microbe interactions in several walnut (Juglans regia) tissues in California using deep RNA-Seq profiling. PMID- 26883052 TI - Behavioral Outcome Effects of Serious Gaming as an Adjunct to Treatment for Children With Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial. AB - BACKGROUND: The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called "Plan-It Commander") as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. METHODS: Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. RESULTS: After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. CONCLUSIONS: Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV). PMID- 26883053 TI - Evaluation and Targeted Therapy of Voiding Dysfunction in Children. AB - Significant strides have been made over the past two decades in more precisely evaluating and managing children with voiding complaints. A thorough history should offer insight into the possible causes for the presenting complaints and this should be supplemented by physical examination, urine studies, and select imaging. Uroflowmetry and external sphincter electromyography with measurement of postvoid residual urine should allow for accurate diagnosis using categories offered by the International Children's Continence Society. This ability to make an accurate diagnosis should naturally lead to the use of treatment options (urotherapy, pharmacotherapy, biofeedback, and neuromodulation) that specifically target the responsible cause of the complaints rather than simply their symptoms. PMID- 26883055 TI - Survey and analysis of simple sequence repeats (SSRs) in three genomes of Candida species. AB - Simple sequence repeats (SSRs) or microsatellites, which composed of tandem repeated short units of 1-6 bp, have been paying attention continuously. Here, the distribution, composition and polymorphism of microsatellites and compound microsatellites were analyzed in three available genomes of Candida species (Candida dubliniensis, Candida glabrata and Candida orthopsilosis). The results show that there were 118,047, 66,259 and 61,119 microsatellites in genomes of C. dubliniensis, C. glabrata and C. orthopsilosis, respectively. The SSRs covered more than 1/3 length of genomes in the three species. The microsatellites, which just consist of bases A and (or) T, such as (A)n, (T)n, (AT)n, (TA)n, (AAT)n, (TAA)n, (TTA)n, (ATA)n, (ATT)n and (TAT)n, were predominant in the three genomes. The length of microsatellites was focused on 6 bp and 9 bp either in the three genomes or in its coding sequences. What's more, the relative abundance (19.89/kbp) and relative density (167.87 bp/kbp) of SSRs in sequence of mitochondrion of C. glabrata were significantly great than that in any one of genomes or chromosomes of the three species. In addition, the distance between any two adjacent microsatellites was an important factor to influence the formation of compound microsatellites. The analysis may be helpful for further studying the roles of microsatellites in genomes' origination, organization and evolution of Candida species. PMID- 26883054 TI - Downregulation of Microrna-126 Contributes to Tumorigenesis of Squamous Tongue Cell Carcinoma via Targeting KRAS. AB - BACKGROUND miR-126 has been reported to be differentially expressed in various malignancies, whereas its role in the pathogenesis of tongue squamous cell carcinoma (TSCC) remains largely unknown. MATERIAL AND METHODS In this study, we collected 21 pairs of TSCC cancerous and adjacent non-cancerous tissue samples, with which we performed real-time PCR to determine and compare the expression of 6 candidate miRNAs that are reportedly associated with tumorigenesis of TSCC, including miR-100, miR-451, miR-221, let-7a, miR-21, and miR-126. We further performed luciferase assay to validate KRAS as a target of miR-126, and conducted transfection to study the effect of miR-126 on proliferation and apoptosis of the cells. RESULTS We identified that miR-126 was significantly downregulated in the cancerous tissue samples compared with the non-cancerous control tissue samples. By using computational analysis, we identified that KRAS is a virtual target of miR-126, and such association was verified by using luciferase assay. In addition, we found that mRNA and protein expression level of KRAS was significantly higher in the tumor tissue than the control tissue samples. CONCLUSIONS The following in vitro experiment showed that both mRNA and protein KRAS expression were significantly decreased in SCC-15 cells in which miR-126 was overexpressed, in comparison with similar cells transfected with a negative control, while downregulation of miR-126 by transfecting the cells with miR-126 inhibitors significantly upregulated the mRNA and protein expression of KRAS. CONCLUSIONS: miR-126 might be a promising diagnostic and therapeutic target in the prevention and management of TSCC patients. PMID- 26883056 TI - Properties of lipid electropores I: Molecular dynamics simulations of stabilized pores by constant charge imbalance. AB - Molecular dynamics (MD) simulations have become a powerful tool to study electroporation (EP) in atomic detail. In the last decade, numerous MD studies have been conducted to model the effect of pulsed electric fields on membranes, providing molecular models of the EP process of lipid bilayers. Here we extend these investigations by modeling for the first time conditions comparable to experiments using long (MUs-ms) low intensity (~kV/cm) pulses, by studying the characteristics of pores formed in lipid bilayers maintained at a constant surface tension and subject to constant charge imbalance. This enables the evaluation of structural (size) and electrical (conductance) properties of the pores formed, providing information hardly accessible directly by experiments. Extensive simulations of EP of simple phosphatidylcholine bilayers in 1M NaCl show that hydrophilic pores with stable radii (1-2.5 nm) form under transmembrane voltages between 420 and 630 mV, allowing for ionic conductance in the range of 6.4-29.5 nS. We discuss in particular these findings and characterize both convergence and size effects in the MD simulations. We further extend these studies in a follow-up paper (Rems et al., Bioelectrochemistry, Submitted), by proposing an improved continuum model of pore conductance consistent with the results from the MD simulations. PMID- 26883057 TI - Revisiting direct electron transfer in nanostructured carbon laccase oxygen cathodes. AB - The biocatalytic electroreduction of oxygen has been studied on large surface area graphite and Vulcan(r) carbon electrodes with adsorbed Trametes trogii laccase. The electrokinetics of the O2 reduction reaction (ORR) was studied at different electrode potentials, O2 partial pressures and concentrations of hydrogen peroxide. Even though the overpotential at 0.25 mA.cm(-2) for the ORR at T1Cu of the adsorbed laccase on carbon is 0.8 V lower than for Pt of similar geometric area, the rate of the reaction and thus the operative current density is limited by the enzyme reaction rate at the T2/T3 cluster site for the adsorbed enzyme. The transition potential for the rate determining step from the direct electron transfer (DET) to the enzyme reaction shifts to higher potentials at higher oxygen partial pressure. Hydrogen peroxide produced by the ORR on bare carbon support participates in an inhibition mechanism, with uncompetitive predominance at high H2O2 concentration, non-competitive contribution can be detected at low inhibitor concentration. PMID- 26883059 TI - Degradation kinetics and metabolites in continuous biodegradation of isoprene. AB - The kinetic parameters of isoprene biodegradation were studied in a bioreactor, comprising of bioscrubber and polyurethane foam packed biofilter in series and inoculated with Pseudomonas sp., using a Michaelis-Menten type model. The maximum elimination capacity, ECmax; substrate constant, Ks and ECmax/Ks values for bioscrubber were found to be 666.7 g m(-3) h(-1), 9.86 g m(-3) and 67.56 h(-1), respectively while those for biofilter were 3333 g m(-3) h(-1), 13.96 g m(-3) and 238.7 h(-1), respectively. The biofilter section exhibited better degradation efficiency compared to the bioscrubber unit. Around 62-75% of the feed isoprene got converted to carbon dioxide, indicating the efficient capability of bacteria to mineralize isoprene. The FTIR and GC-MS analyses of degradation products indicated oxidative cleavage of unsaturated bond of isoprene. These results were used for proposing a plausible degradation pathway for isoprene. PMID- 26883058 TI - Mothering a Preterm Infant Receiving NIDCAP Care in a Level III Newborn Intensive Care Unit. AB - The purpose of the study is to describe the unique meaning and significance of the essential elements of mothering a preterm infant receiving Newborn Individualized Developmental Care and Assessment Program (NIDCAP) care in a level III NICU. The overall aim was to promote an increased understanding among healthcare practitioners of the experience of this group of women. DESIGN AND METHODS: The authors utilized an existential-phenomenologic method to investigate the experience of 7 mothers of a preterm infant 30weeks gestation or less at birth. RESULTS: Analysis of interview transcripts revealed one overarching theme, parenting with permission, and three essential themes with nine underlying subthemes: choosing to participate (subthemes: managing, settling in, making friends), dealing with people (subthemes: meeting needs, facing judgment, and recognizing not everyone is 'on board,' and coming to feel like a mother (subthemes: overcoming fear, gaining understanding, and feeling empowered). CONCLUSIONS/PRACTICE IMPLICATIONS: Mothers universally praised NIDCAP for the education and support it provided them. However findings also suggest that great sensitivity and patience is required by professionals to assist mothers to overcome their fear, gain confidence, and participate in NIDCAP without feeling judged. In addition private rooms were found to hold great significance for mothers and should be maintained for the entire hospitalization whenever possible. Finally, ongoing NIDCAP education/support for staff and regular team meetings to discuss and problem-solve concerns are suggested. This might address inconsistent adherence to the NIDCAP care plan by some nurses, which is the greatest source of maternal conflict and frustration. PMID- 26883060 TI - Gradient packing bed bio-filter for landfill methane mitigation. AB - We assessed the suitability of various biogenic materials for development of a gradient packed bed bio-filter to mitigate the methane (CH4) emission from landfills. Five different biogenic materials (windrow compost-WC; vermicompost VC; landfill top cover-LTC; landfill bottom soil-LBS; and river soil sediment-SS) were screened. Among these materials, the VC showed a better CH4 oxidation potential (MOP) of 12.6MUg CH4 gdw(-1)h(-1). Subsequently, the VC was used as a packing material along with wood chips in proto-type bio-filters. Wood chips were mixed at 5-15% to form three distinct gradients in a test bio-filter. Under the three different CH4 loading rates of 33, 44 and 55 gCH4 m(-3)h(-1), the achieved MOPs were 31, 41, and 47gCH4 m(-3)h(-1), respectively. The gradient packed bed bio-filter is effective for landfill CH4 mitigation than the conventional bio filter as the latter shows gas channeling effects with poor MOPs. PMID- 26883062 TI - Perceived time and temporal structure: Neural entrainment to isochronous stimulation increases duration estimates. AB - Distortions of perceived duration can give crucial insights into the mechanisms that underlie the processing and representation of stimulus timing. One factor that affects duration estimates is the temporal structure of stimuli that fill an interval. For example, regular filling (isochronous interval) leads to an overestimation of perceived duration as compared to irregular filling (anisochronous interval). In the present article, we use electroencephalography (EEG) to investigate the neural basis of this subjective lengthening of perceived duration with isochrony. In a two-interval forced choice task, participants judged which of two intervals lasts longer - one always being isochronous, the other one anisochronous. Response proportions confirm the subjective overestimation of isochronous intervals. At the neural level, isochronous sequences are associated with enhanced pairwise phase consistency (PPC) at the stimulation frequency, reflecting the brain's entrainment to the regular stimulation. The PPC over the entrainment channels is further enhanced for isochronous intervals that are reported to be longer, and the magnitude of this PCC effect correlates with the amount of perceptual bias. Neural entrainment has been proposed as a mechanism of attentional selection, enabling increased neural responsiveness toward stimuli that arrive at an expected point in time. The present results support the proposed relationship between neural response magnitudes and temporal estimates: An increase in neural responsiveness leads to a more pronounced representation of the individual stimuli filling the interval and in turn to a subjective increase in duration. PMID- 26883063 TI - The role of the neural reward circuitry in self-referential optimistic belief updates. AB - People are motivated to adopt the most favorable beliefs about their future because positive beliefs are experienced as rewarding. However, it is so far inconclusive whether brain regions known to represent reward values are involved in the generation of optimistically biased belief updates. To address this question, we investigated neural correlates of belief updates that result in relatively better future outlooks, and therefore imply a positive subjective value of the judgment outcome. Participants estimated the probability of experiencing different adverse future events. After being provided with population base rates of these events, they had the opportunity to update their initial estimates. Participants made judgments concerning themselves or a similar other, and were confronted with desirable or undesirable base rates (i.e., lower or higher than their initial estimates). Belief updates were smaller following undesirable than desirable information, and this optimism bias was stronger for judgments regarding oneself than others. During updating, the positive value of self-related updates was reflected by neural activity in the subgenual ventromedial prefrontal cortex (vmPFC) that increased both with increasing sizes of favorable updates, and with decreasing sizes of unfavorable updates. During the processing of self-related undesirable base rates, increasing activity in a network including the dorsomedial PFC, hippocampus, thalamus and ventral striatum predicted decreasing update sizes. Thus, key regions of the neural reward circuitry contributed to the generation of optimistically biased self-referential belief updates. While the vmPFC tracked subjective values of belief updates, a network including the ventral striatum was involved in neglecting information calling for unfavorable updates. PMID- 26883061 TI - ETP-46321, a dual p110alpha/delta class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. AB - Class IA phosphoinositide 3-kinases (PI3Ks) are essential to function of normal and tumor cells, and to modulate immune responses. T lymphocytes express high levels of p110alpha and p110delta class IA PI3K. Whereas the functioning of PI3K p110delta in immune and autoimmune reactions is well established, the role of p110alpha is less well understood. Here, a novel dual p110alpha/delta inhibitor (ETP-46321) and highly specific p110alpha (A66) or p110delta (IC87114) inhibitors have been compared concerning T cell activation in vitro, as well as the effect on responses to protein antigen and collagen-induced arthritis in vivo. In vitro activation of naive CD4(+) T lymphocytes by anti-CD3 and anti-CD28 was inhibited more effectively by the p110delta inhibitor than by the p110alpha inhibitor as measured by cytokine secretion (IL-2, IL-10, and IFN-gamma), T-bet expression and NFAT activation. In activated CD4(+) T cells re-stimulated through CD3 and ICOS, IC87114 inhibited Akt and Erk activation, and the secretion of IL-2, IL-4, IL 17A, and IFN-gamma better than A66. The p110alpha/delta inhibitor ETP-46321, or p110alpha plus p110delta inhibitors also inhibited IL-21 secretion by differentiated CD4(+) T follicular (Tfh) or IL-17-producing (Th17) helper cells. In vivo, therapeutic administration of ETP-46321 significantly inhibited responses to protein antigen as well as collagen-induced arthritis, as measured by antigen-specific antibody responses, secretion of IL-10, IL-17A or IFN-gamma, or clinical symptoms. Hence, p110alpha as well as p110delta Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis. PMID- 26883064 TI - Avatars and arrows in the brain. AB - In this Commentary article we critically assess the claims made by Schurz, Kronbichler, Weissengrubler, Surtees, Samson and Perner (2015) relating to the neural processes underlying theory of mind and visual perspective taking. They attempt to integrate research findings in these two areas of social neuroscience using a perspective taking task contrasting mentalistic agents ('avatars'), with non-mentalistic control stimuli ('arrows'), during functional Magnetic Resonance Imaging. We support this endeavour whole-heartedly, agreeing that the integration of findings in these areas has been neglected in research on the social brain. However, we cannot find among the behavioural or neuroimaging data presented by Schurz et al. evidence supporting their claim of 'implicit mentalizing'-the automatic ascription of mental states to another representing what they can see. Indeed, we suggest that neuroimaging methods may be ill-suited to address the existence of implicit mentalizing, and suggest that approaches utilizing neurostimulation methods are likely to be more successful. PMID- 26883065 TI - Decoding the neural representation of fine-grained conceptual categories. AB - Neuroscientific research on conceptual knowledge based on the grounded cognition framework has shed light on the organization of concrete concepts into semantic categories that rely on different types of experiential information. Abstract concepts have traditionally been investigated as an undifferentiated whole, and have only recently been addressed in a grounded cognition perspective. The present fMRI study investigated the involvement of brain systems coding for experiential information in the conceptual processing of fine-grained semantic categories along the abstract-concrete continuum. These categories consisted of mental state-, emotion-, mathematics-, mouth action-, hand action-, and leg action-related meanings. Thirty-five sentences for each category were used as stimuli in a 1-back task performed by 36 healthy participants. A univariate analysis failed to reveal category-specific activations. Multivariate pattern analyses, in turn, revealed that fMRI data contained sufficient information to disentangle all six fine-grained semantic categories across participants. However, the category-specific activity patterns showed no overlap with the regions coding for experiential information. These findings demonstrate the possibility of detecting specific patterns of neural representation associated with the processing of fine-grained conceptual categories, crucially including abstract ones, though bearing no anatomical correspondence with regions coding for experiential information as predicted by the grounded cognition hypothesis. PMID- 26883066 TI - Reverse inference of memory retrieval processes underlying metacognitive monitoring of learning using multivariate pattern analysis. AB - Monitoring of learning is only accurate at some time after learning. It is thought that immediate monitoring is based on working memory, whereas later monitoring requires re-activation of stored items, yielding accurate judgements. Such interpretations are difficult to test because they require reverse inference, which presupposes specificity of brain activity for the hidden cognitive processes. We investigated whether multivariate pattern classification can provide this specificity. We used a word recall task to create single trial examples of immediate and long term retrieval and trained a learning algorithm to discriminate them. Next, participants performed a similar task involving monitoring instead of recall. The recall-trained classifier recognized the retrieval patterns underlying immediate and long term monitoring and classified delayed monitoring examples as long-term retrieval. This result demonstrates the feasibility of decoding cognitive processes, instead of their content. PMID- 26883068 TI - Transcranial direct current stimulation changes resting state functional connectivity: A large-scale brain network modeling study. AB - Transcranial direct current stimulation (tDCS) is a noninvasive technique for affecting brain dynamics with promising application in the clinical therapy of neurological and psychiatric disorders such as Parkinson's disease, Alzheimer's disease, depression, and schizophrenia. Resting state dynamics increasingly play a role in the assessment of connectivity-based pathologies such as Alzheimer's and schizophrenia. We systematically applied tDCS in a large-scale network model of 74 cerebral areas, investigating the spatiotemporal changes in dynamic states as a function of structural connectivity changes. Structural connectivity was defined by the human connectome. The main findings of this study are fourfold: Firstly, we found a tDCS-induced increase in functional connectivity among cerebral areas and among EEG sensors, where the latter reproduced empirical findings of other researchers. Secondly, the analysis of the network dynamics suggested synchronization to be the main mechanism of the observed effects. Thirdly, we found that tDCS sharpens and shifts the frequency distribution of scalp EEG sensors slightly towards higher frequencies. Fourthly, new dynamic states emerged through interacting areas in the network compared to the dynamics of an isolated area. The findings propose synchronization as a key mechanism underlying the changes in the spatiotemporal pattern formation due to tDCS. Our work supports the notion that noninvasive brain stimulation is able to bias brain dynamics by affecting the competitive interplay of functional subnetworks. PMID- 26883067 TI - Identification and individualized prediction of clinical phenotypes in bipolar disorders using neurocognitive data, neuroimaging scans and machine learning. AB - Diagnosis, clinical management and research of psychiatric disorders remain subjective - largely guided by historically developed categories which may not effectively capture underlying pathophysiological mechanisms of dysfunction. Here, we report a novel approach of identifying and validating distinct and biologically meaningful clinical phenotypes of bipolar disorders using both unsupervised and supervised machine learning techniques. First, neurocognitive data were analyzed using an unsupervised machine learning approach and two distinct clinical phenotypes identified namely; phenotype I and phenotype II. Second, diffusion weighted imaging scans were pre-processed using the tract-based spatial statistics (TBSS) method and 'skeletonized' white matter fractional anisotropy (FA) and mean diffusivity (MD) maps extracted. The 'skeletonized' white matter FA and MD maps were entered into the Elastic Net machine learning algorithm to distinguish individual subjects' phenotypic labels (e.g. phenotype I vs. phenotype II). This calculation was performed to ascertain whether the identified clinical phenotypes were biologically distinct. Original neurocognitive measurements distinguished individual subjects' phenotypic labels with 94% accuracy (sensitivity=92%, specificity=97%). TBSS derived FA and MD measurements predicted individual subjects' phenotypic labels with 76% and 65% accuracy respectively. In addition, individual subjects belonging to phenotypes I and II were distinguished from healthy controls with 57% and 92% accuracy respectively. Neurocognitive task variables identified as most relevant in distinguishing phenotypic labels included; Affective Go/No-Go (AGN), Cambridge Gambling Task (CGT) coupled with inferior fronto-occipital fasciculus and callosal white matter pathways. These results suggest that there may exist two biologically distinct clinical phenotypes in bipolar disorders which can be identified from healthy controls with high accuracy and at an individual subject level. We suggest a strong clinical utility of the proposed approach in defining and validating biologically meaningful and less heterogeneous clinical sub phenotypes of major psychiatric disorders. PMID- 26883069 TI - Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives. AB - Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology. PMID- 26883070 TI - Peptide Reactivity of Isothiocyanates--Implications for Skin Allergy. AB - Skin allergy is a chronic condition that affects about 20% of the population of the western world. This disease is caused by small reactive compounds, haptens, able to penetrate into the epidermis and modify endogenous proteins, thereby triggering an immunogenic reaction. Phenyl isothiocyanate (PITC) and ethyl isothiocyanate (EITC) have been suggested to be responsible for allergic skin reactions to chloroprene rubber, the main constituent of wetsuits, orthopedic braces, and many types of sports gear. In the present work we have studied the reactivity of the isothiocyanates PITC, EITC, and tetramethylrhodamine-6 isothiocyanate (6-TRITC) toward peptides under aqueous conditions at physiological pH to gain information about the types of immunogenic complexes these compounds may form in the skin. We found that all three compounds reacted quickly with cysteine moieties. For PITC and 6-TRITC the cysteine adducts decomposed over time, while stable adducts with lysine were formed. These experimental findings were verified by DFT calculations. Our results may suggest that the latter are responsible for allergic reactions to isothiocyanates. The initial adduct formation with cysteine residues may still be of great importance as it prevents hydrolysis and facilitates the transport of isothiocyanates into epidermis where they can form stable immunogenic complexes with lysine-containing proteins. PMID- 26883072 TI - Reply. PMID- 26883071 TI - Universality of slip avalanches in flowing granular matter. AB - The search for scale-bridging relations in the deformation of amorphous materials presents a current challenge with tremendous applications in material science, engineering and geology. While generic features in the flow and microscopic dynamics support the idea of a universal scaling theory of deformation, direct microscopic evidence remains poor. Here, we provide the first measurement of internal scaling relations in the deformation of granular matter. By combining macroscopic force fluctuation measurements with internal strain imaging, we demonstrate the existence of robust scaling relations from particle-scale to macroscopic flow. We identify consistent power-law relations truncated by systematic pressure-dependent cutoff, in agreement with recent mean-field theory of slip avalanches in elasto-plastic materials, revealing the existence of a mechanical critical point. These results experimentally establish scale-bridging relations in the flow of matter, paving the way to a new universal theory of deformation. PMID- 26883074 TI - Branched-Chain Amino Acids and Cardiovascular Disease: Does Diet Matter? PMID- 26883073 TI - STAT1 and NF-kappaB Inhibitors Diminish Basal Interferon-Stimulated Gene Expression and Improve the Productive Infection of Oncolytic HSV in MPNST Cells. AB - Interferon-stimulated genes (ISG) encode diverse proteins that mediate intrinsic antiviral resistance in infected cells. Here it was hypothesized that malignant peripheral nerve sheath tumor (MPNST) cells resist the productive infection of oncolytic herpes simplex virus (oHSV) through activation of the JAK/STAT1 pathway and resultant upregulation of ISGs. Multiple human and mouse MPNST cells were used to explore the relationship between STAT1 activation and the productive infection of Deltagamma134.5 oHSVs. STAT1 activation in response to oHSV infection was found to associate with diminished Deltagamma134.5 oHSVs replication and spread. Multiday pretreatment, but not cotreatment, with a JAK inhibitor significantly improved viral titer and spread. ISG expression was found to be elevated prior to infection and downregulated when treated with the inhibitor, suggesting that the JAK/STAT1 pathway is active prior to infection. Conversely, upregulation of ISG expression in normally permissive cells significantly decreased oHSV productivity. Finally, a possible link between NF kappaB pathway activation and ISG expression was established through the expression of inhibitor of kB (IkappaB) which decreased basal STAT1 transcription and ISG expression. These results demonstrate that basal ISG expression prior to infection contributes to the resistance of Deltagamma134.5 oHSVs in MPNST cells. IMPLICATIONS: Although cancer-associated ISG expression has been previously reported to impart resistance to chemotherapy and radiotherapy, these data show that basal ISG expression also contributes to oncolytic HSV resistance. Mol Cancer Res; 14(5); 482-92. (c)2016 AACR. PMID- 26883075 TI - High-flow nasal cannula oxygen and nasal continuous positive airway pressure and full oral feeding in infants with bronchopulmonary dysplasia. AB - OBJECTIVE: To determine whether the time to achieve full oral feeding differed between infants with bronchopulmonary dysplasia (BPD) supported by nasal continuous positive airway pressure (nCPAP) compared with those supported by nCPAP and subsequently transferred to heated, humidified, high-flow nasal cannula oxygen (HHFNC). DESIGN: Two-cohort comparison. SETTING: Tertiary neonatal unit. PATIENTS: -72 infants, median gestational age 27 (range 24-32) weeks in the nCPAP group, and 44 infants, median gestational age 27 (range 24-31) weeks in the nCPAP/HHFNC group. INTERVENTIONS: Between 2011 and 2013, infants post extubation were supported by nCPAP and from 2013 infants were supported by nCPAP and then HHFNC. MAIN OUTCOME MEASURES: The postnatal age at which oral feeds were first trialled and full oral feeds established. The length of respiratory support as either nCPAP or nCPAP/HHFNC and the total length of respiratory support and hospital stay were also determined. Subanalysis was undertaken of infants requiring respiratory support beyond 34 weeks postmenstrual age (PMA). RESULTS: The postnatal age at trial of first oral feeds was earlier in the nCPAP/HHFNC group (p=0.012), but infants were a shorter time on nCPAP compared with nCPAP/HHFNC (p=0.003). On subgroup analysis, the age to achieve full oral feeds was earlier in the nCPAP/HHFNC group (p<0.001). CONCLUSIONS: In infants with BPD who required respiratory support beyond 34 weeks PMA, use of nCPAP then HHFNC was associated with earlier establishment of full oral feeds. Consideration should be given to assessing stable BPD infants with regard to oral feeding while on CPAP. PMID- 26883076 TI - The Association of Poor Mental Health Status and Sociocultural Factors in Men: A Population-Based Study in Tehran, Iran. AB - Mental ill-health has increased among Iranian men in the recent years. Mental health is complexly determined by sociocultural, psychological, demographic characteristics, and some health-risk behaviors such as smoking. This study aimed to explore the association(s) between demographic factors, smoking status, social capital, and poor mental health status in a sample of Iranian men. The data were derived from a survey titled "Urban Health Equity Assessment and Response Tool-2" in Tehran, Iran ( n = 11,064). A multistage sampling method was applied in the study. The General Health Questionnaire-28 was used to assess poor mental health status (range = 0-84, scores higher than 23 indicated poor mental health status). The data were analyzed using t test, chi-square test, and multivariate logistic regression. The means of age and family size were 47.14 +/- 17.26 years (range = 20-91) and 3.54 +/- 1.32 individuals (range = 1-15), respectively. The majority of the participants were employed (57%, n = 6,361). The prevalence of poor mental health was 36.36%, 95% confidence interval (CI) [35.46, 37.26]. The components of social capital were positively associated with poor mental health status. Family size (adjusted odds ratio [AOR] = 0.93; 95% CI [0.90, 0.96]), job status (unemployed vs. employed, AOR = 1.34; 95% CI [1.16, 1.55]), marital status (widowed and divorced vs. single, AOR = 1.09; 95% CI [1.02, 1.17]), education level (illiterate vs. academic, AOR = 1.18; 95% CI [1.09, 1.29]), and smoking status (smokers vs. nonsmokers, AOR = 1.46; 95% CI [1.31, 1.62]) were directly associated with poor mental health status in the logistic regression model. These results suggest that social capital could be an important approach for men to attain suitable mental health and reduce mental disorders. The high prevalence of poor mental health in men merits more attention in mental health policy and program planning. PMID- 26883078 TI - Folic acid to prevent neural tube defects: another solution. PMID- 26883079 TI - Fit to WHO weight standard of European infants over time. AB - OBJECTIVES: The 2006 WHO growth charts were created to provide an international standard for optimal growth, based on healthy, breastfed populations, but it has been suggested that Northern European children fit them poorly. This study uses infant weight data spanning 50 years to determine how well-nourished preschool children from different eras fit the WHO standard, and discuss the implications of deviations. DESIGN: Four longitudinal datasets from the UK and one from Finland were used comprising over 8000 children born between 1959 and 2003. Weights from birth to 2 years were converted to age-sex-adjusted Z scores using the WHO standard and summarised using Generalized Additive Models for Location, Scale and Shape. RESULTS: Weights showed a variable fit to the WHO standard. Mean weights for all cohorts were above the WHO median at birth, but dipped by up to 0.5 SD to a nadir at 8 weeks before rising again. Birth weights increased in successive cohorts and the initial dip became slightly shallower. By age 1 year, cohorts were up to 0.75 SD above the WHO median, but there was no consistent pattern by era. CONCLUSIONS: The WHO standard shows an acceptable, but variable fit for Northern European infants. While birth weights increased over time, there was, unexpectedly, no consistent variation by cohort beyond this initial period. Discrepancies in weight from the standard may reflect differences in measurement protocol and trends in infant feeding practice. PMID- 26883080 TI - Trace analysis of multi-class pesticide residues in Chinese medicinal health wines using gas chromatography with electron capture detection. AB - A method is described for multi-residue, high-throughput determination of trace levels of 22 organochlorine pesticides (OCPs) and 5 pyrethroid pesticides (PYPs) in Chinese medicinal (CM) health wines using a QuEChERS (quick, easy, cheap, effective, rugged, and safe) based extraction method and gas chromatography electron capture detection (GC-ECD). Several parameters were optimized to improve preparation and separation time while still maintaining high sensitivity. Validation tests of spiked samples showed good linearities for 27 pesticides (R = 0.9909-0.9996) over wide concentration ranges. Limits of detection (LODs) and quantification (LOQs) were measured at ng/L levels, 0.06-2 ng/L and 0.2-6 ng/L for OCPs and 0.02-3 ng/L and 0.06-7 ng/L for PYPs, respectively. Inter- and intra day precision tests showed variations of 0.65-9.89% for OCPs and 0.98-13.99% for PYPs, respectively. Average recoveries were in the range of 47.74-120.31%, with relative standard deviations below 20%. The developed method was then applied to analyze 80 CM wine samples. Beta-BHC (Benzene hexachloride) was the most frequently detected pesticide at concentration levels of 5.67-31.55 mg/L, followed by delta-BHC, trans-chlordane, gamma-BHC, and alpha-BHC. The validated method is simple and economical, with adequate sensitivity for trace levels of multi-class pesticides. It could be adopted by laboratories for this and other types of complex matrices analysis. PMID- 26883081 TI - A novel biliary stent coated with silver nanoparticles prolongs the unobstructed period and survival via anti-bacterial activity. AB - Symptomatic biliary stricture causes life-threatening complications, such as jaundice, recurrent cholangitis and secondary biliary cirrhosis. Fully covered self-expanding metal stents (FCSEMSs) are gaining acceptance for treatments of benign biliary stricture and palliative management of malignant biliary obstructions. However, the high rate of FCSEMS obstruction limits their clinic use. In this study, we developed a novel biliary stent coated with silver nanoparticles (AgNPs) and investigated its efficacy both in vitro and in vivo. We first identified properties of the AgNP complex using ultraviolet detection. The AgNP complex was stable without AgNP agglomeration, and Ag abundance was correspondingly increased with an increased bilayer number. The AgNP biliary stent demonstrated good performance in the spin-assembly method based on topographic observation. The AgNP biliary stent also exhibited a long-term anti coagulation effect and a slow process of Ag(+) release. In vitro anti-bacteria experiments indicated that the AgNP biliary stent exhibited high-efficiency anti bacterial activity for both short- and long-term periods. Importantly, application of the AgNP biliary stent significantly prolonged the unobstructed period of the biliary system and improved survival in preclinical studies as a result of its anti-microbial activity and decreased granular tissue formation on the surface of the anastomotic biliary, providing a novel and effective treatment strategy for symptomatic biliary strictures. PMID- 26883082 TI - HIV coreceptor tropism determination and mutational pattern identification. AB - In the early stages of infection, Human Immunodeficiency Virus Type 1 (HIV-1) generally selects CCR5 as the primary coreceptor for entering the host cell. As infection progresses, the virus evolves and may exhibit a coreceptor-switch to CXCR4. Accurate determination coreceptor usage and identification key mutational patterns associated tropism switch are essential for selection of appropriate therapies and understanding mechanism of coreceptor change. We developed a classifier composed of two coreceptor-specific weight matrices (CMs) based on a full-scale dataset. For this classifier, we found an AUC of 0.97, an accuracy of 95.21% and an MCC of 0.885 (sensitivity 92.92%; specificity 95.54%) in a ten-fold cross-validation, outperforming all other methods on an independent dataset (13% higher MCC value than geno2pheno and 15% higher MCC value than PSSM). A web server (http://spg.med.tsinghua.edu.cn/CM.html) based on our classifier was provided. Patterns of genetic mutations that occur along with coreceptor transitions were further identified based on the score of each sequence. Six pairs of one-AA mutational patterns and three pairs of two-AA mutational patterns were identified to associate with increasing propensity for X4 tropism. These mutational patterns offered new insights into the mechanism of coreceptor switch and aided in monitoring coreceptor switch. PMID- 26883083 TI - Impact of Angiotensin I-converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC. AB - It has been shown that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can decrease tumor growth and tumor-associated angiogenesis and inhibit metastasis. Epidermal growth factor receptor (EGFR) mutations are found in approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) in East Asia and in 10-15% of such patients in Western countries. We retrospectively identified 228 patients with histologically confirmed advanced NSCLC and 73 patients with early stage disease; 103 of these patients took antihypertensive drugs, and 112 received treatment with EGFR tyrosine kinase inhibitors (TKIs). There was a significant difference in progression-free survival after first-line therapy (PFS1) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients treated with TKIs, there was a significant difference in PFS but not in overall survival (OS) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients with advanced NSCLC, there was a significant difference in PFS1 between the ACEI/ARB group and the non ACEI/ARB group. ACEI/ARB in combination with standard chemotherapy or TKIs had a positive effect on PFS1 or OS, regardless of whether the lung cancer was in the early or advanced stage. PMID- 26883085 TI - Sampling Depths, Depth Shifts, and Depth Resolutions for Bi(n)(+) Ion Analysis in Argon Gas Cluster Depth Profiles. AB - Gas cluster sputter depth profiling is increasingly used for the spatially resolved chemical analysis and imaging of organic materials. Here, a study is reported of the sampling depth in secondary ion mass spectrometry depth profiling. It is shown that effects of the sampling depth leads to apparent shifts in depth profiles of Irganox 3114 delta layers in Irganox 1010 sputtered, in the dual beam mode, using 5 keV Ar2000+ ions and analyzed with Bi(q+), Bi3(q+) and Bi5(q+) ions (q = 1 or 2) with energies between 13 and 50 keV. The profiles show sharp delta layers, broadened from their intrinsic 1 nm thickness to full widths at half-maxima (fwhm's) of 8-12 nm. For different secondary ions, the centroids of the measured delta layers are shifted deeper or shallower by up to 3 nm from the position measured for the large, 564.36 Da (C33H46N3O5-) characteristic ion for Irganox 3114 used to define a reference position. The shifts are linear with the Bi(n)(q+) beam energy and are greatest for Bi3(q+), slightly less for Bi5(q+) with its wider or less deep craters, and significantly less for Bi(q+) where the sputtering yield is very low and the primary ion penetrates more deeply. The shifts increase the fwhm's of the delta layers in a manner consistent with a linearly falling generation and escape depth distribution function (GEDDF) for the emitted secondary ions, relevant for a paraboloid shaped crater. The total depth of this GEDDF is 3.7 times the delta layer shifts. The greatest effect is for the peaks with the greatest shifts, i.e. Bi3(q+) at the highest energy, and for the smaller fragments. It is recommended that low energies be used for the analysis beam and that carefully selected, large, secondary ion fragments are used for measuring depth distributions, or that the analysis be made in the single beam mode using the sputtering Ar cluster ions also for analysis. PMID- 26883086 TI - Plasmon Excitations of Multi-layer Graphene on a Conducting Substrate. AB - We predict the existence of low-frequency nonlocal plasmons at the vacuum-surface interface of a superlattice of N graphene layers interacting with conducting substrate. We derive a dispersion function that incorporates the polarization function of both the graphene monolayers and the semi-infinite electron liquid at whose surface the electrons scatter specularly. We find a surface plasmon polariton that is not damped by particle-hole excitations or the bulk modes and which separates below the continuum mini-band of bulk plasmon modes. The surface plasmon frequency of the hybrid structure always lies below omegas = omegap/?2, the surface plasmon frequency of the conducting substrate. The intensity of this mode depends on the distance of the graphene layers from the conductor's surface, the energy band gap between valence and conduction bands of graphene monolayer and, most importantly, on the number of two-dimensional layers. For a sufficiently large number of layers (N >= 7) the hybrid structure has no surface plasmon. The existence of plasmons with different dispersion relations indicates that quasiparticles with different group velocity may coexist for various ranges of wavelengths determined by the number of layers in the superlattice. PMID- 26883084 TI - ARTD1 regulates osteoclastogenesis and bone homeostasis by dampening NF-kappaB dependent transcription of IL-1beta. AB - While ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) and its enzymatic activity have been shown to be important for reprogramming and differentiation of cells, such as during adipogenesis, their role and mechanism in regulating osteoclastogenesis and bone homeostasis are largely unknown. Here, in cell culture-based RANKL-induced osteoclastogenesis models, we show that silencing of ARTD1 or inhibition of its enzymatic activity enhances osteoclast differentiation and function. As a consequence of ARTD1 silencing or inhibition, the recruitment of p65/RelA to the IL-1beta promoter, which is associated with transcriptionally active histone marks, IL-1beta expression and inflammasome dependent secretion of IL-1beta are enhanced. This subsequently promotes sustained induction of the transcription factor Nfatc1/A and osteoclastogenesis in an autocrine manner via the IL-1 receptor. In vivo, Artd1-deficient mice display significantly decreased bone mass as a consequence of increased osteoclast differentiation. Accordingly, the expression of osteoclast markers is enhanced in mutant compared to wild-type mice. Together, these results indicate that ARTD1 controls osteoclast development and bone remodelling via its enzymatic activity by modulating the epigenetic marks surrounding the IL-1beta promoter and expression of IL-1beta and subsequently also Nfatc1/A. PMID- 26883087 TI - Elimination and Concentration Correlations between Edible Tissues and Biological Fluids and Hair of Ractopamine in Pigs and Goats Fed with Ractopamine-Medicated Feed. AB - Ractopamine (RAC), a beta-adrenergic leanness-enhancing agent, endangers the food safety of animal products because of overdosing and illegal use in food animals. Excretion and residue depletion of RAC in pigs and goats were investigated to determine a representative biological fluid or surface tissue for preslaughter monitoring. After a single oral gavage of RAC, 64-67% of the dose was excreted from the urine of pigs and goats within 12-24 h. RAC persisted the longest in the hair of pigs and goats but depleted rapidly in the plasma, muscle, and fat. Urine and hair were excellent for predicting RAC residues in edible tissues of pigs, whereas plasma and urine were satisfactory body fluids for the prediction of RAC concentrations in edible tissues of goats. These data provided a simple and economical preslaughter living monitoring method for the illegal use and violative residue of RAC in food animals. PMID- 26883088 TI - Cryptococcus neoformans Thermotolerance to Avian Body Temperature Is Sufficient For Extracellular Growth But Not Intracellular Survival In Macrophages. AB - Cryptococcus neoformans is a fatal fungal pathogen of humans that efficiently parasitises macrophages. Birds can be colonised by cryptococci and can transmit cryptococcosis to humans via inhalation of inoculated bird excreta. However, colonisation of birds appears to occur in the absence of symptomatic infection. Here, using a pure population of primary bird macrophages, we demonstrate a mechanism for this relationship. We find that bird macrophages are able to suppress the growth of cryptococci seen in mammalian cells despite C. neoformans being able to grow at bird body temperature, and are able to escape from bird macrophages by vomocytosis. A small subset of cryptococci are able to adapt to the inhibitory intracellular environment of bird macrophages, exhibiting a large cell phenotype that rescues growth suppression. Thus, restriction of intracellular growth combined with survival at bird body temperature explains the ability of birds to efficiently spread C. neoformans in the environment whilst avoiding systemic disease. PMID- 26883090 TI - Comment on "Virtues and limitations of Pittsburgh green for ozone detection" by C. C. Beltran, E. A. Palmer, B. R. Buckley and F. Iza, Chem. Commun., 2015, 51, 1579. AB - We previously developed Pittsburgh Green homoallyl ether to quantify trace ozone. Independently, problems were reported when the method was used for excess ozone. Here, we discuss the origin of the reported problems and demonstrate that when this method is used according to our previous report, no problems occur. PMID- 26883089 TI - Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects. AB - Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin. PMID- 26883091 TI - Heritability of non-speech auditory processing skills. AB - Recent insight into the genetic bases for autism spectrum disorder, dyslexia, stuttering, and language disorders suggest that neurogenetic approaches may also reveal at least one etiology of auditory processing disorder (APD). A person with an APD typically has difficulty understanding speech in background noise despite having normal pure-tone hearing sensitivity. The estimated prevalence of APD may be as high as 10% in the pediatric population, yet the causes are unknown and have not been explored by molecular or genetic approaches. The aim of our study was to determine the heritability of frequency and temporal resolution for auditory signals and speech recognition in noise in 96 identical or fraternal twin pairs, aged 6-11 years. Measures of auditory processing (AP) of non-speech sounds included backward masking (temporal resolution), notched noise masking (spectral resolution), pure-tone frequency discrimination (temporal fine structure sensitivity), and nonsense syllable recognition in noise. We provide evidence of significant heritability, ranging from 0.32 to 0.74, for individual measures of these non-speech-based AP skills that are crucial for understanding spoken language. Identification of specific heritable AP traits such as these serve as a basis to pursue the genetic underpinnings of APD by identifying genetic variants associated with common AP disorders in children and adults. PMID- 26883094 TI - Role of dose exposure and inflammatory status in a single center, real-world analysis of sunitinib in patients with metastatic renal cell carcinoma. AB - AIM, PATIENTS & METHODS: To evaluate the real-world setting use of sunitinib, we reviewed data of our patients from January 2007 to December 2014. RESULTS: In 114 patients, sunitinib was used as first-line TKI. Out of 110 evaluable patients, 5 complete responses, 37 partial responses, 42 stabilizations were reported. Median progression-free survival and overall survival (OS) were 14.3 and 28.4 months. Patients who received >= 4 full-dose cycles had a better OS (p = 0.02). A neutrophil-lymphocyte ratio <3 was associated both with OS and progression-free survival (50.4 vs 8.4 and 20.0 vs 3.3 months). CONCLUSION: Sunitinib is active and feasible. Patients receiving <4 full-dose cycles or having increased neutrophil-lymphocyte ratio achieved worse outcomes: therefore, these are present potential predictive factors. PMID- 26883092 TI - A family-based, genome-wide association study of young-onset breast cancer: inherited variants and maternally mediated effects. AB - Young-onset breast cancer shows certain phenotypic and etiologic differences from older-onset breast cancer and may be influenced by some distinct genetic variants. Few genetic studies of breast cancer have targeted young women and no studies have examined whether maternal variants influence disease in their adult daughters through prenatal effects. We conducted a family-based, genome-wide association study of young-onset breast cancer (age at diagnosis <50 years). A total of 602 188 single-nucleotide polymorphisms (SNPs) were genotyped for 1279 non-Hispanic white cases and their parents or sisters. We used likelihood-based log-linear models to test for transmission asymmetry within families and for maternally mediated genetic effects. Three autosomal SNPs (rs28373882, P=2.8 * 10(-7); rs879162, P=9.2 * 10(-7); rs12606061, P=9.1 * 10(-7)) were associated with risk of young-onset breast cancer at a false-discovery rate below 0.20. None of these loci has been previously linked with young-onset or overall breast cancer risk, and their functional roles are unknown. There was no evidence of maternally mediated, X-linked, or mitochondrial genetic effects, and no notable findings within cancer subcategories defined by menopausal status, estrogen receptor status, or by tumor invasiveness. Further investigations are needed to explore other potential genetic, epigenetic, or epistatic mechanisms and to confirm the association between these three novel loci and young-onset breast cancer. PMID- 26883093 TI - Congenital protein losing enteropathy: an inborn error of lipid metabolism due to DGAT1 mutations. AB - Protein-losing enteropathy (PLE) is a clinical disorder of protein loss from the gastrointestinal system that results in hypoproteinemia and malnutrition. This condition is associated with a wide range of gastrointestinal disorders. Recently, a unique syndrome of congenital PLE associated with biallelic mutations in the DGAT1 gene has been reported in a single family. We hypothesize that mutations in this gene are responsible for undiagnosed cases of PLE in infancy. Here we investigated three children in two families presenting with severe diarrhea, hypoalbuminemia and PLE, using clinical studies, homozygosity mapping, and exome sequencing. In one family, homozygosity mapping using SNP arrays revealed the DGAT1 gene as the best candidate gene for the proband. Sequencing of all the exons including flanking regions and promoter regions of the gene identified a novel homozygous missense variant, p.(Leu295Pro), in the highly conserved membrane-bound O-acyl transferase (MBOAT) domain of the DGAT1 protein. Expression studies verified reduced amounts of DGAT1 in patient fibroblasts. In a second family, exome sequencing identified a previously reported splice site mutation in intron 8. These cases of DGAT1 deficiency extend the molecular and phenotypic spectrum of PLE, suggesting a re-evaluation of the use of DGAT1 inhibitors for metabolic disorders including obesity and diabetes. PMID- 26883095 TI - DNA methylation-induced E-cadherin silencing is correlated with the clinicopathological features of melanoma. AB - E-cadherin, a calcium-dependent cell-cell adhesion molecule, has an important role in epithelial cell function, maintenance of tissue architecture and cancer suppression. Loss of E-cadherin promotes tumor metastatic dissemination and predicts poor prognosis. The present study investigated the clinicopathological significance of E-cadherin expression in cutaneous, mucosal and uveal melanoma related to epigenetic mechanisms that may contribute to E-cadherin silencing. E cadherin expression was reduced in 55/130 cutaneous (42.3%), 49/82 mucosal (59.7%) and 36/64 uveal (56.2%) melanoma samples as compared to normal skin controls and was inversely associated with promoter methylation. Of the 10 different CpG sites studied (nt 863, 865, 873, 879, 887, 892, 901, 918, 920 and 940), two sites (nt 892 and 940) were 90-100% methylated in all the melanoma specimens examined and the other ones were partially methylated (range, 53-86%). In contrast, the methylation rate of the E-cadherin gene was low in normal tissues (range, 5-24%). In all the three types of melanoma studied, a significant correlation was found between reduced levels of E-cadherin and reduced survival, high mitotic index and metastasis, accounting for the predilection of lymph nodal localization. In cutaneous and mucosal melanoma, low E-cadherin expression was positively correlated also with head/neck localization and ulceration. A high frequency of reduced E-cadherin levels occurred in choroid melanomas. In vitro experiments showed that E-cadherin transcription was restored following 5-aza-2' deoxycytidine (5-aza-dC) treatment or DNMT1 silencing and was negatively correlated with the invasive potential of melanoma cells. The significant relationship between E-cadherin silencing and several poor prognostic factors indicates that this adhesion molecule may play an important role in melanomagenesis. Therefore, the inverse association of E-cadherin expression with promoter methylation raises the intriguing possibility that reactivation of E cadherin expression through promoter demethylation may represent a potential therapeutic strategy for the treatment of melanoma. PMID- 26883097 TI - A three-dimensional integrated nanogenerator for effectively harvesting sound energy from the environment. AB - An integrated triboelectric nanogenerator (ITNG) with a three-dimensional structure benefiting sound propagation and adsorption is demonstrated to more effectively harvest sound energy with improved output performance. With different multifunctional integrated layers working harmonically, it could generate a short circuit current up to 2.1 mA, an open-circuit voltage up to 232 V and the maximum charging rate can reach 453 MUC s(-1) for a 1 mF capacitor, which are 4.6 times, 2.6 times and 7.4 times the highest reported values, respectively. Further study shows that the ITNG works well under sound in a wide range of sound intensity levels (SILs) and frequencies, and its output is sensitive to the SIL and frequency of the sound, which reveals that the ITNG can act as a self-powered active sensor for real-time noise surveillance and health care. Moreover, this generator can be used to directly power the Fe(OH)3 sol electrophoresis and shows great potential as a wireless power supply in the electrochemical industry. PMID- 26883096 TI - Psychological reactance and HIV-related stigma among women living with HIV. AB - Psychological reactance is defined as the drive to re-establish autonomy after it has been threatened or constrained. People living with HIV may have high levels of psychological reactance due to the restrictions that they may perceive as a result of living with HIV. People living with HIV may also exhibit levels of HIV related stigma. The relationship between psychological reactance and HIV-related stigma is complex yet understudied. Therefore, the main aim of this study was to examine the association between psychological reactance and HIV-related stigma among women living with HIV. Data were obtained from one time-point (a cross sectional assessment) of a longitudinal HIV disclosure study. Psychological reactance was measured using the 18-item Questionnaire for the Measurement of Psychological Reactance. HIV-related stigma was measured using the HIV Stigma Scale, which has four domains: personalized, disclosure concerns, negative self image, and concerns with public attitudes. Principal component analysis was used to derive components of psychological reactance. Linear regression models were used to determine the association between overall psychological reactance and its components, and stigma and its four domains, and depressive and anxiety symptoms. The associations between stigma and mental health were also examined. Three components of psychological reactance were derived: Opposition, Irritability, and Independence. Overall psychological reactance and irritability were associated with all forms of stigma. Opposition was linked to overall and negative self image stigma. Overall psychological reactance, opposition, and irritability were positively associated with anxiety symptoms while opposition was also associated with Centers for Epidemiologic Studies-Depression depressive symptoms. There were also positive associations between all forms of stigma, and depressive and anxiety symptoms. Health-care providers and counselors for women living with HIV addressing feelings of irritability and opposition toward others may reduce HIV related stigma. Future research should examine the link between psychological reactance, mental health, and HIV-related stigma among other populations living with HIV. PMID- 26883098 TI - The PQRS-Montreal: a measure of patients' perceptions of the quality of rehabilitation services for persons with a traumatic brain injury. AB - Purpose To determine the factorial validity, internal consistency, criterion related and concurrent validity of the Perception of Quality of Rehabilitation Services - Montreal (PQRS-Montreal) questionnaire for persons receiving traumatic brain injury (TBI) rehabilitation services. Design Cross-sectional study. Setting Seventeen facilities providing acute care and intensive inpatient and outpatient TBI adult rehabilitation. Participants Five-hundred thirty adults (GCS = 3-15; mean age = 41.5 +/- 16.9 years) who received rehabilitation were administered the questionnaire during an interview near time of discharge. Subjects responded to the 61 PQRS-Montreal items (five-point scale of agreement) and to the Client Satisfaction Question (CSQ8). Results Exploratory and confirmatory factor analyses identified three potential subscales (one- and two-factor solutions) explaining 26.1-41% of the variance (ecological approach, quality of team, service organization). The subscales' internal structures were interpretable and their internal consistency varied from 0.51 to 0.90 (Cronbach's alpha). Rehabilitation phase significantly and positively impacted factor scores and all factor scores were significantly and moderately correlated with CSQ8 scores. Conclusions The PQRS-Montreal possesses adequate psychometric properties supporting its use as a valid tool to measure patients' perception of the quality of TBI rehabilitation services. This tool could help guide the development and monitoring of TBI rehabilitation service delivery. Implications for Rehabilitation The importance of measuring and monitoring quality of care is increasingly important in rehabilitation. Using the experiences and perceptions of care of service users is a valid way of assessing the quality of rehabilitation services. The PQRS-Montreal has adequate psychometric properties supporting its use as a valid tool to measure patients' perception of the quality of TBI rehabilitation services. This tool could help guide the development and monitoring of TBI rehabilitation service delivery. PMID- 26883099 TI - Digestion and absorption of an egg white ACE-inhibitory peptide in human intestinal Caco-2 cell monolayers. AB - The objective of this study was to investigate the digestion and absorption of egg white-derived angiotensin I-converting enzyme (ACE)-inhibitory peptide TNGIIR in human intestinal Caco-2 cell monolayers. Results showed that the digestion of TNGIIR to simulated gastrointestinal enzymes and brush border membrane peptidases were 5.87% +/- 1.92% and 17.17% +/- 0.64%, respectively (p < 0.05). The apparent permeability coefficients (P(app)) of TNGIIR from the apical to basolateral side in Caco-2 cell monolayers was determined to be (4.92 +/- 0.40) * 10(-6) cm/s, indicating that TNGIIR can transport across Caco-2 cell monolayers in intact form. In addition, only cytochalasin D, a disruptor of tight junctions (TJs), changed TNGIIR transport rate significantly (p < 0.05), suggesting that the main transport route for TNGIIR across Caco-2 cell monolayers was paracellular pathway via TJs. PMID- 26883100 TI - Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission. AB - Cytomegalovirus (CMV)-reactivation is associated with graft-vs-leukemia (GVL) effect by stimulating natural-killer or T-cells, which showed leukemia relapse prevention after hematopoietic stem cell transplantation (HSCT). We enrolled patients with acute myeloid leukemia (n = 197) and acute lymphoid leukemia (n = 192) who underwent allogeneic-HSCT in first remission. We measured RQ-PCR weekly to detect CMV-reactivation and preemptively used ganciclovir (GCV) when the titer increased twice consecutively, but GCV was sometimes delayed in patients without significant graft-vs-host disease (GVHD) by reducing immunosuppressive agents. In the entire group, CMV-reactivation showed poor overall survival (OS). To evaluate subsequent effects of CMV-reactivation, we excluded early relapse and deaths within 100 days, during which most of the CMV-reactivation occurred. Untreated CMV-reactivated group (n = 173) showed superior OS (83.8% vs. 61.7% vs. 74.0%, p < 0.001) with lower relapse rate (10.1% vs 22.1% vs. 25.5%, p = 0.004) compared to GCV-treated CMV-reactivated group (n = 122) and CMV-undetected group (n = 42). After excluding chronic GVHD, untreated CMV-reactivated group still showed lower relapse rate (9.4% vs. 24.1% vs. 30.2%, p = 0.006). Multivariate analysis showed adverse-risk karyotype and patients in other than untreated CMV-reactivated group were independent factors for relapse prediction. Our data showed possible GVL effect of CMV-reactivation and minimizing antiviral therapy may benefit for relapse prevention in acute leukemia. PMID- 26883101 TI - Synergic interaction between amyloid precursor protein and neural cell adhesion molecule promotes neurite outgrowth. AB - Alzheimer's disease (AD) is one of the most common neurodegenerative diseases worldwide. The main features of AD are the pathological changes of density and distribution of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques. The processing of amyloid beta precursor protein (APP) to beta amyloid peptide (Abeta) is one of the critical events in the pathogenesis of AD. In this study, we evaluated the role of the interaction of neural cell adhesion molecule (NCAM) and APP in neurite outgrowth using two different experimental systems: PC12E2 cells and hippocampal neurons that were isolated from wild type, APP knock-in and APP knock-out mice. PC12E2 cells or hippocampal neurons were co cultured with NCAM-negative or NCAM-positive fibroblasts L929 cells. We found that APP promoted neurite outgrowth of PC12E2 cells and hippocampal neurons in either the presence or absence of NCAM. Secreted APP can rescue the neurite outgrowth in hippocampal neurons from APP knock-out mice. The interaction of APP and NCAM had synergic effect in promoting neurite outgrowth in both PC12E2 cells and hippocampal neurons. Our results suggested that the interaction of APP with NCAM played an important role in AD development and therefore could be a potential therapeutic target for AD treatment. PMID- 26883102 TI - Myeloid neoplasms with isolated isochromosome 17q demonstrate a high frequency of mutations in SETBP1, SRSF2, ASXL1 and NRAS. AB - Isolated isochromosome 17q, i(17q), accounts for less than 1% of myeloid neoplasms that are commonly classified as myelodysplastic/myeloproliferative neoplasms, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN). We have shown previously that these cases have distinctive clinicopathologic features, a poor prognosis and absence of TP53 mutations. However, their molecular mutation profile has not been studied. Here, we explored the mutation profile of 32 cases of myeloid neoplasm with isolated i(17q) that included AML, MDS/MPN, MDS and MPN. In addition to the common i(17q), these neoplasms had frequent mutations in SRSF2 (55%), SETBP1 (59%), ASXL1 (55%), and NRAS (31%); TET2 and TP53 mutations were rare. Eight of 28 patients (29%) showed concurrent mutations in ASXL1, SRSF2, SETBP1 and RAS. There was a significant association between mutations in SETBP1 and RAS (p = 0.003). The mutation pattern was independent of the morphologic diagnosis. Sequential analysis of 5 cases showed evolution from a diploid karyotype to i(17q) and that SRSF2 and ASXL1 mutations precede the detection of i(17q) whereas SETBP1 mutations are associated with i(17q). PMID- 26883103 TI - Withaferin-A suppress AKT induced tumor growth in colorectal cancer cells. AB - The oncogenic activation of AKT gene has emerged as a key determinant of the aggressiveness of colorectal cancer (CRC); hence, research has focused on targeting AKT signaling for the treatment of advanced stages of CRC. In this study, we explored the anti-tumorigenic effects of withaferin A (WA) on CRC cells overexpressing AKT in preclinical (in vitro and in vivo) models. Our results indicated that WA, a natural compound, resulted in significant inhibition of AKT activity and led to the inhibition of cell proliferation, migration and invasion by downregulating the epithelial to mesenchymal transition (EMT) markers in CRC cells overexpressing AKT. The oral administration of WA significantly suppressed AKT-induced aggressive tumor growth in a xenograft model. Molecular analysis revealed that the decreased expression of AKT and its downstream pro-survival signaling molecules may be responsible for tumor inhibition. Further, significant inhibition of some important EMT markers, i.e., Snail, Slug, beta-catenin and vimentin, was observed in WA-treated human CRC cells overexpressing AKT. Significant inhibition of micro-vessel formation and the length of vessels were evident in WA-treated tumors, which correlated with a low expression of the angiogenic marker RETIC. In conclusion, the present study emphasizes the crucial role of AKT activation in inducing cell proliferation, angiogenesis and EMT in CRC cells and suggests that WA may overcome AKT-induced cell proliferation and tumor growth in CRC. PMID- 26883104 TI - Prognostic and therapeutic role of targetable lesions in B-lineage acute lymphoblastic leukemia without recurrent fusion genes. AB - To shed light into the molecular bases of B-lineage acute lymphoblastic leukemia lacking known fusion transcripts, i.e. BCR-ABL1, ETV6-RUNX1, E2A-PBX1, and MLL rearrangements (B-NEG ALL) and the differences between children, adolescents/young adults (AYA) and adults, we analyzed 168 B-NEG ALLs by genome wide technologies. This approach showed that B-NEG cases carry 10.5 mutations and 9.1 copy-number aberrations/sample. The most frequently mutated druggable pathways were those pertaining to RAS/RTK (26.8%) and JAK/STAT (12.5%) signaling. In particular, FLT3 and JAK/STAT mutations were detected mainly in AYA and adults, while KRAS and NRAS mutations were more frequent in children. RAS/RTK mutations negatively affected the outcome of AYA and adults, but not that of children. Furthermore, adult B-NEG ALL carrying JAK/STAT mutations had a shorter survival. In vitro experiments showed that FLT3 inhibitors reduced significantly the proliferation of FLT3-mutated primary B-NEG ALL cells. Likewise, PI3K/mTOR inhibitors reduced the proliferation of primary cells harboring RAS and IL7R mutations. These results refine the genetic landscape of B-NEG ALL and suggest that the different distribution of lesions and their prognostic impact might sustain the diverse outcome between children, adults and partly AYA - whose genomic scenario is similar to adults - and open the way to targeted therapeutic strategies. PMID- 26883105 TI - An alternatively spliced variant of CXCR3 mediates the metastasis of CD133+ liver cancer cells induced by CXCL9. AB - Metastasis of liver cancer is closely linked to tumor microenvironment, in which chemokines and their receptors act in an important role. The CXCR3, the receptor of chemokine CXCL9, belongs to a superfamily of rhodopsin-like seven transmembrane GPCRs and CXCR subfamily. In HCC tissues, CXCR3 was frequently upregulated and correlated with tumor size, tumor differentiation, portal invasion and metastasis. In the study, CXCR3-A isoform that was bound by CXCL9 was found to cause significant change of ERK1/2 phosphorylation level in the MAPK signaling pathway, consequently upregulating the MMP2 and MMP9 expression and promoting invasion and metastasis of CD133+ liver cancer cells. Also, CXCR3-A suppressed the adhesion ability of CD133+ liver cancer cells that stimulated by CXCL9 for 24h. These findings suggest that CXCR3 and its ligand CXCL9 could promote the metastasis of liver cancer cells and might be a potential target for the intervention of liver cancer metastasis. PMID- 26883106 TI - Cross-platform comparison of independent datasets identifies an immune signature associated with improved survival in metastatic melanoma. AB - Platform and study differences in prognostic signatures from metastatic melanoma (MM) gene expression reports often hinder consensus arrival. We performed survival/outcome-based pairwise comparisons of three independent MM gene expression profiles using the threshold-free algorithm rank-rank hypergeometric overlap analysis (RRHO). We found statistically significant overlap for genes overexpressed in favorable outcome (FO) groups, but no overlap for poor outcome (PO) groups. This "favorable outcome signature" (FOS) of 228 genes coinciding on all three overlapping gene lists showed immune function predominated in FO MM. Surprisingly, specific cell signature-enrichment analysis showed B cell associated genes enriched in FO MM, along with T cell-associated genes. Higher levels of B and T cells (p<0.05) and their relative proximity (p<0.05) were detected in FO-to-PO tumor comparisons from an independent MM patients cohort. Finally, expression of FOS in two independent Stage III MM tumor datasets correctly predicted clinical outcome in 12/14 and 44/70 patients using a weighted gene voting classifier (area under the curve values 0.96 and 0.75, respectively). This RRHO-based, cross-study analysis emphasizes the RRHO approach power, confirms T cells relevance for prolonged MM survival, supports a favorable role for B cells in anti-melanoma immunity, and suggests B cells potential as means of intervention in melanoma treatment. PMID- 26883107 TI - Porcine circovirus type 2 activates PI3K/Akt and p38 MAPK pathways to promote interleukin-10 production in macrophages via Cap interaction of gC1qR. AB - Porcine circovirus type 2 (PCV2) infection caused PCV2-associated diseases (PCVAD) is one of the major emerging immunosuppression diseases in pig industry. In this study, we investigated how PCV2 inoculation increases interleukin (IL)-10 expression in porcine alveolar macrophages (PAMs). PCV2 inoculation significantly upregulated IL-10 expression compared with PCV1. Upon initial PCV2 inoculation, PI3K/Akt cooperated with NF-kappaB pathways to promote IL-10 transcription via p50, CREB and Ap1 transcription factors, whereas inhibition of PI3K/Akt activation blocked Ap1 and CREB binding to the il10 promoter, and decreased the binding level of NF-kappaB1 p50 with il10 promoter, leading to great reduction in early IL-10 transcription. In the later phase of inoculation, PCV2 further activated p38 MAPK and ERK pathways to enhance IL-10 production by promoting Sp1 binding to the il10 promoter. For PCV2-induced IL-10 production in macrophages, PCV2 capsid protein Cap, but not the replicase Rep or ORF3, was the critical component. Cap activated PI3K/Akt, p38 MAPK, and ERK signaling pathways to enhance IL-10 expression. In the whole process, gC1qR mediated PCV2-induced PI3K/Akt and p38 MAPK activation to enhance IL-10 induction by interaction with Cap. Depletion of gC1qR blocked PI3K/Akt and p38 MAPK activation, resulting in significant decrease in IL-10 production in PCV2-inoculated cells. Thus, gC1qR might be a critical functional receptor for PCV2-induced IL-10 production. Taken together, these data demonstrated that Cap protein binding with host gC1qR induction of PI3K/Akt and p38 MAPK signalings activation is a critical process in enhancing PCV2-induced IL-10 production in porcine alveolar macrophages. PMID- 26883109 TI - Antibody h-R3-dendrimer mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion. AB - The major obstacle to developing siRNA delivery is their extracellular and intracellular barriers. Herein, a humanized anti-EGFR monoclonal antibody h-R3 was developed to modify the self-assembled binary complexes (dendriplexes) of PAMAM and siRNA via electrostatic interactions, and two common ligands HSA and EGF were used as a control. Compared to dendriplexes, h-R3/EGF/HSA-dendriplexes showed increased particle size, decreased zeta potentials and lower cytotoxicity. Moreover, h-R3-dendriplexes presented greater cellular uptake and excellent endosomal escape ability in HepG2 cells. Ex vivo fluorescence imaging revealed that h-R3-dendriplexes showed higher targeted delivery and gene expression in the tumors than dendriplexes, HSA-dendriplexes and EGF-dendriplexes, which was in agreement with confocal results of cryosections. Furthermore, h-R3-dendriplexes for siPLK1 delivery indicated efficient gene silencing, potentiated cell growth inhibition and cell apoptosis, and suppressed cellular migration/invasion. These results indicate that h-R3-dendriplexes represent a great potential to be used as efficient targeted siRNA delivery carriers. PMID- 26883108 TI - Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3. AB - PP2C family serine/threonine phosphatase WIP1 acts as a negative regulator of the tumor suppressor p53 and is implicated in silencing of cellular responses to genotoxic stress. Chromosomal locus 17q23 carrying the PPM1D (coding for WIP1) is commonly amplified in breast carcinomas and WIP1 was proposed as potential pharmacological target. Here we employed a cellular model with knocked out PPM1D to validate the specificity and efficiency of GSK2830371, novel small molecule inhibitor of WIP1. We have found that GSK2830371 increased activation of the DNA damage response pathway to a comparable level as the loss of PPM1D. In addition, GSK2830371 did not affect proliferation of cells lacking PPM1D but significantly supressed proliferation of breast cancer cells with amplified PPM1D. Over time cells treated with GSK2830371 accumulated in G1 and G2 phases of the cell cycle in a p21-dependent manner and were prone to induction of senescence by a low dose of MDM2 antagonist nutlin-3. In addition, combined treatment with GSK2830371 and doxorubicin or nutlin-3 potentiated cell death through a strong induction of p53 pathway and activation of caspase 9. We conclude that efficient inhibition of WIP1 by GSK2830371 sensitizes breast cancer cells with amplified PPM1D and wild type p53 to chemotherapy. PMID- 26883111 TI - Targeting endothelial connexin40 inhibits tumor growth by reducing angiogenesis and improving vessel perfusion. AB - Endothelial connexin40 (Cx40) contributes to regulate the structure and function of vessels. We have examined whether the protein also modulates the altered growth of vessels in tumor models established in control mice (WT), mice lacking Cx40 (Cx40-/-), and mice expressing the protein solely in endothelial cells (Tie2 Cx40). Tumoral angiogenesis and growth were reduced, whereas vessel perfusion, smooth muscle cell (SMC) coverage and animal survival were increased in Cx40-/- but not Tie2-Cx40 mice, revealing a critical involvement of endothelial Cx40 in transformed tissues independently of the hypertensive status of Cx40-/- mice. As a result, Cx40-/- mice bearing tumors survived significantly longer than corresponding controls, including after a cytotoxic administration. Comparable observations were made in WT mice injected with a peptide targeting Cx40, supporting the Cx40 involvement. This involvement was further confirmed in the absence of Cx40 or by peptide-inhibition of this connexin in aorta-sprouting, matrigel plug and SMC migration assays, and associated with a decreased expression of the phosphorylated form of endothelial nitric oxide synthase. The data identify Cx40 as a potential novel target in cancer treatment. PMID- 26883110 TI - Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds. AB - Inactivation of the p53 transcription factor by mutation or other mechanisms is a frequent event in tumorigenesis. One of the major endogenous negative regulators of p53 in humans is hDM2, a ubiquitin E3 ligase that binds to p53 causing proteasomal p53 degradation. In this work, a library of organometallic iridium(III) compounds were synthesized and evaluated for their ability to disrupt the p53/hDM2 protein-protein interaction. The novel cyclometallated iridium(III) compound 1 [Ir(eppy)2(dcphen)](PF6) (where eppy = 2-(4 ethylphenyl)pyridine and dcphen = 4, 7-dichloro-1, 10-phenanthroline) blocked the interaction of p53/hDM2 in human amelanotic melanoma cells. Finally, 1 exhibited anti-proliferative activity and induced apoptosis in cancer cell lines consistent with inhibition of the p53/hDM2 interaction. Compound 1 represents the first reported organometallic p53/hDM2 protein-protein interaction inhibitor. PMID- 26883112 TI - Involvement of calprotectin (S100A8/A9) in molecular pathways associated with HNSCC. AB - Calprotectin (S100A8/A9), a heterodimeric protein complex of calcium-binding proteins S100A8 and S100A9, plays key roles in cell cycle regulation and inflammation, with potential functions in squamous cell differentiation. While upregulated in many cancers, S100A8/A9 is downregulated in squamous cell carcinomas of the cervix, esophagus, and the head and neck (HNSCC). We previously reported that ectopic S100A8/A9 expression inhibits cell cycle progression in carcinoma cells. Here, we show that declining expression of S100A8/A9 in patients with HNSCC is associated with increased DNA methylation, less differentiated tumors, and reduced overall survival. Upon ectopic over-expression of S100A8/A9, the cancer phenotype of S100A8/A9-negative carcinoma cells was suppressed in vitro and tumor growth in vivo was significantly decreased. MMP1, INHBA, FST, LAMC2, CCL3, SULF1, and SLC16A1 were significantly upregulated in HNSCC but were downregulated by S100A8/A9 expression. Our findings strongly suggest that downregulation of S100A8/A9 through epigenetic mechanisms may contribute to increased proliferation, malignant transformation, and disease progression in HNSCC. PMID- 26883113 TI - Distinct features between MLH1-methylated and unmethylated colorectal carcinomas with the CpG island methylator phenotype: implications in the serrated neoplasia pathway. AB - The presence or absence of MLH1 methylation may critically affect the heterogeneity of colorectal carcinoma (CRC) with the CpG island methylator phenotype (CIMP). Here, we investigated the differential characteristics of CIMP high (CIMP-H) CRCs according to MLH1 methylation status. To further confirm the MLH1-dependent features in CIMP-H CRC, an independent analysis was performed using data from The Cancer Genome Atlas (TCGA). In our CIMP-H CRC samples, MLH1 methylated tumors were characterized by older patient age, proximal colonic location, mucinous histology, intense lymphoid reactions, RUNX3/SOCS1 promoter methylation, BRAF mutations, and microsatellite instability-high (MSI-H) status. By contrast, MLH1-unmethylated tumors were associated with earlier age of onset, increased distal colorectal localization, adverse pathologic features, and KRAS mutations. In the TCGA dataset, the MLH1-silenced CIMP-H CRC demonstrated proximal location, MSI-H status, hypermutated phenotype, and frequent BRAF mutations, but the MLH1-non-silenced CIMP-H CRC was significantly associated with high frequencies of KRAS and APC mutations. In conclusion, the differential nature of CIMP-H CRCs depends primarily on the MLH1 methylation status. Based on the current knowledge, the sessile serrated adenoma/polyp may be the major precursor of MLH1-methylated CIMP-H CRCs, whereas MLH1-unmethylated CIMP-H CRCs may develop predominantly from KRAS-mutated traditional serrated adenomas and less commonly from BRAF-mutated traditional serrated adenomas and/or sessile serrated adenomas/polyps. PMID- 26883114 TI - NAB2-STAT6 Gene Fusion in Meningeal Hemangiopericytoma and Solitary Fibrous Tumor. AB - Meningeal solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are considered to be distinct entities in the WHO Classification of CNS Tumours (2007). They harbor NAB2-STAT6 fusions similar to their soft tissue counterparts, supporting the view that they are part of a tumor continuum. We examined 30 meningeal-based tumors originally diagnosed as either SFT or HPC. These showed a spectrum of morphologic features and were diagnosed as SFTs, malignant SFTs, HPCs, or tumors with "intermediate" features. All of the tumors showed nuclear expression of STAT6. SFTs consistently expressed diffuse CD34, while HPCs and intermediate tumors had heterogeneous staining. NAB2-STAT6 fusions were identified in 20 cases, including 7 with exon 4-exon 3, 9 with exon 6-exon 17, and 4 with exon 6-exon 18 fusions. NAB2 exon 4-STAT6 exon 3 fusion correlated with classic SFT morphology and older age and showed a trend toward less mitotic activity; there was also a trend toward more aggressive behavior in tumors lacking NAB2 exon 4-STAT6 exon 3. Thus, despite their clinical and morphologic differences, meningeal-based SFTs, HPCs, and tumors with intermediate features, similar to their soft tissue counterparts, form a histopathologic spectrum unified by STAT6 immunoexpression and NAB2-STAT6 fusion. PMID- 26883115 TI - Assessment of Quantitative and Allelic MGMT Methylation Patterns as a Prognostic Marker in Glioblastoma. AB - Methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene is a predictive and prognostic marker in newly diagnosed glioblastoma patients treated with temozolomide but how MGMT methylation should be assessed to ensure optimal detection accuracy is debated. We developed a novel quantitative methylation specific PCR (qMSP) MGMT assay capable of providing allelic methylation data and analyzed 151 glioblastomas from patients receiving standard of care treatment (Stupp protocol). The samples were also analyzed by immunohistochemistry (IHC), standard bisulfite pyrosequencing, and genotyped for the rs1690252 MGMT promoter single nucleotide polymorphism. Monoallelic methylation was observed more frequently than biallelic methylation, and some cases with monoallelic methylation expressed the MGMT protein whereas others did not. The presence of MGMT methylation was associated with better overall survival (p = 0.006; qMSP and p = 0.002; standard pyrosequencing), and the presence of the protein was associated with worse overall survival (p = 0.009). Combined analyses of qMSP and standard pyrosequencing or IHC identified additional patients who benefited from temozolomide treatment. Finally, low methylation levels were also associated with better overall survival (p = 0.061; qMSP and p = 0.02; standard pyrosequencing). These data support the use of both MGMT methylation and MGMT IHC but not allelic methylation data as prognostic markers in patients with temozolomide-treated glioblastoma. PMID- 26883116 TI - Widespread RNA binding by chromatin-associated proteins. AB - BACKGROUND: Recent evidence suggests that RNA interaction can regulate the activity and localization of chromatin-associated proteins. However, it is unknown if these observations are specialized instances for a few key RNAs and chromatin factors in specific contexts, or a general mechanism underlying the establishment of chromatin state and regulation of gene expression. RESULTS: Here, we perform formaldehyde RNA immunoprecipitation (fRIP-Seq) to survey the RNA associated with a panel of 24 chromatin regulators and traditional RNA binding proteins. For each protein that reproducibly bound measurable quantities of bulk RNA (90% of the panel), we detect enrichment for hundreds to thousands of both noncoding and mRNA transcripts. CONCLUSION: For each protein, we find that the enriched sets of RNAs share distinct biochemical, functional, and chromatin properties. Thus, these data provide evidence for widespread specific and relevant RNA association across diverse classes of chromatin-modifying complexes. PMID- 26883117 TI - MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties. AB - BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. METHODS: We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. RESULTS: Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. CONCLUSIONS: This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma. PMID- 26883118 TI - Evaluating a complex model designed to increase access to high quality primary mental health care for under-served groups: a multi-method study. AB - BACKGROUND: Many people with mental distress are disadvantaged because care is not available or does not address their needs. In order to increase access to high quality primary mental health care for under-served groups, we created a model of care with three discrete elements: community engagement, primary care training and tailored wellbeing interventions. We have previously demonstrated the individual impact of each element of the model. Here we assess the effectiveness of the combined model in increasing access to and improving the quality of primary mental health care. We test the assumptions that access to the wellbeing interventions is increased by the presence of community engagement and primary care training; and that quality of primary mental health care is increased by the presence of community engagement and the wellbeing interventions. METHODS: We implemented the model in four under-served localities in North-West England, focusing on older people and minority ethnic populations. Using a quasi-experimental design with no-intervention comparators, we gathered a combination of quantitative and qualitative information. Quantitative information, including referral and recruitment rates for the wellbeing interventions, and practice referrals to mental health services, was analysed descriptively. Qualitative information derived from interview and focus group responses to topic guides from more than 110 participants. Framework analysis was used to generate findings from the qualitative data. RESULTS: Access to the wellbeing interventions was associated with the presence of the community engagement and the primary care training elements. Referrals to the wellbeing interventions were associated with community engagement, while recruitment was associated with primary care training. Qualitative data suggested that the mechanisms underlying these associations were increased awareness and sense of agency. The quality of primary mental health care was enhanced by information gained from our community mapping activities, and by the offer of access to the wellbeing interventions. There were variable benefits from health practitioner participation in community consultative groups. We also found that participation in the wellbeing interventions led to increased community engagement. CONCLUSIONS: We explored the interactions between elements of a multilevel intervention and identified important associations and underlying mechanisms. Further research is needed to test the generalisability of the model. TRIAL REGISTRATION: Current Controlled Trials, reference ISRCTN68572159 . Registered 25 February 2013. PMID- 26883120 TI - Marmoricola ginsengisoli sp. nov. and Marmoricola pocheonensis sp. nov. isolated from a ginseng-cultivating field. AB - Two novel actinobacteria, designated strains Gsoil 097T and Gsoil 818T, isolated from soil of a ginseng field, South Korea, were characterized by a polyphasic approach to clarify their taxonomic positions. They were Gram-reaction-positive, aerobic, non-spore-forming and rod-shaped. Phylogenetic analysis based on 16S rRNA gene sequences indicated that both isolates belong to the genus Marmoricola and were related most closely to Marmicola solisilvae KIS18-7T (99.1 and 98.3 % similarity, respectively), Marmicola terrae JOS5-1T (97.9 and 97.9 %), Marmicola scoriae Sco-D01T (97.8 and 97.1 %) and Marmicola aequoreus SST-45T (97.5 and 97.0 %). The G+C content of the genomic DNA was 68.8 and 70.0 mol%, respectively. Both strains were characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H4) as the predominant menaquinone and C17 : 1omega6c, C18 : 1omega9c, C18 : 0 10-methyl and iso-C16 : 0 as major fatty acids. These chemotaxonomic data supported the affiliation of both strains to the genus Marmoricola. However, levels of DNA-DNA relatedness between the two strains and closely related type strains of Marmoricola species were less than 30 %. Moreover, the results of physiological and biochemical tests allowed the phenotypic differentiation of strains Gsoil 097T and Gsoil 818T from other Marmoricola species with validly published names. Therefore, the two isolates represent two novel species, for which the names Marmoricola ginsengisoli sp. nov. (type strain Gsoil 097T = KACC 14267T = DSM 22772T) and Marmoricola pocheonensis sp. nov. (type strain Gsoil 818T = KACC 14275T = DSM 22773T) are proposed. PMID- 26883119 TI - Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. AB - BACKGROUND: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg * 2, but some data have suggested similar clinical efficacy with 500 mg * 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. METHODS: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. RESULTS: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg * 2 and 500 mg * 2, respectively. Patients treated with 500 mg * 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg * 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 +/- SD -2.0 +/- 1.3 (high dose) vs. -1.7 +/- 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). CONCLUSIONS: In this large observational cohort initial treatment with RTX at 500 mg * 2 and 1000 mg * 2 led to comparable clinical outcomes at 6 months. PMID- 26883122 TI - Minimally invasive direct coronary artery bypass grafting with an improved rib spreader and a new-shaped cardiac stabilizer: results of 200 consecutive cases in a single institution. AB - BACKGROUND: Performing minimally invasive direct coronary artery bypass (MIDCAB) grafting via small chest incisions on a beating heart is challenging. We report our experiences of MIDCAB with the utilization of both an improved rib spreader to harvest the left internal mammary artery (LIMA) and a new-shaped cardiac stabilizer to facilitate LIMA-left anterior descending (LAD) coronary anastomosis. METHODS: Between May 2012 and June 2104, a total of 200 patients who were consecutively operated on in this period were enrolled in this study. Data reported included demographic information, preoperative clinical and cardiac status, LIMA harvest time, postoperative in-hospital outcomes, and 30-day mortality. RESULTS: The average LIMA harvest time was 43 min. The mean age was 62.59 +/- 10.19 years, and 45 of the 200 were females. The 30-day mortality was 0.5% (one patient) due to perioperative myocardial infarction. Duration of mechanical ventilation and length of stay in intensive care unit was 9.27 +/- 7.65 and 24.27 +/- 17.85 h, respectively. The unit of packed RBC transfusion was 0.79 +/- 1.58. Postoperative atrial fibrillation was observed in 14 (7%) patients. There was no postoperative stroke, renal failure, or incision complication. CONCLUSION: Performing MIDCAB with the improved retractor and stabilizer utilized in this study showed favorable outcomes in terms of harvesting the LIMA, postoperative morbidities, and 30-day mortality. PMID- 26883124 TI - Highly-sensitive Eu(3+) ratiometric thermometers based on excited state absorption with predictable calibration. AB - Temperature measurements ranging from a few degrees to a few hundreds of Kelvin are of great interest in the fields of nanomedicine and nanotechnology. Here, we report a new ratiometric luminescent thermometer using thermally excited state absorption of the Eu(3+) ion. The thermometer is based on the simple Eu(3+) energy level structure and can operate between 180 and 323 K with a relative sensitivity ranging from 0.7 to 1.7% K(-1). The thermometric parameter is defined as the ratio between the emission intensities of the (5)D0 -> (7)F4 transition when the (5)D0 emitting level is excited through the (7)F2 (physiological range) or (7)F1 (down to 180 K) level. Nano and microcrystals of Y2O3:Eu(3+) were chosen as a proof of concept of the operational principles in which both excitation and detection are within the first biological transparent window. A novel and of paramount importance aspect is that the calibration factor can be calculated from the Eu(3+) emission spectrum avoiding the need for new calibration procedures whenever the thermometer operates in different media. PMID- 26883123 TI - Reconstruction of a charge balanced genome-scale metabolic model to study the energy-uncoupled growth of Zymomonas mobilis ZM1. AB - Zymomonas mobilis is an ethanologenic bacterium and is known to be an example microorganism with energy-uncoupled growth. A genome-scale metabolic model could be applicable for understanding the characteristics of Z. mobilis with rapid catabolism and inefficient energy conversion. In this study, a charge balanced genome-scale metabolic model (iEM439) of Z. mobilis ATCC 10988 (ZM1) including 439 genes, 692 metabolic reactions and 658 metabolites was reconstructed based on genome annotation and previously published information. The model presents a much better prediction for biomass and ethanol concentrations in a batch culture by using dynamic flux balance analysis compared with the two previous genome-scale metabolic models. Furthermore, intracellular flux distribution obtained from the model was consistent with the fluxes for glucose fermentation determined by (13)C NMR. The model predicts that there is no difference in growth rates of Z. mobilis under aerobic and anaerobic conditions whereas ethanol production is decreased and production of other metabolites including acetate and acetoin is increased under aerobic conditions. Experimental data confirm the predicted differences between the aerobic and anaerobic growth of Z. mobilis. Finally, the model was used to study the energy-uncoupled growth of Z. mobilis and to predict its effect on flux distribution in the central metabolism. Flux distribution obtained from the model indicates that coupling growth and energy reduces ethanol secretion and changes the flux distribution to produce more biomass. This coupling is also associated with a significant increase in the proton uptake rate based on the prediction of the charge balanced model. Hence, resistance to intracellular pH reduction could be the main reason for uncoupled growth and Z. mobilis uses ATPase to pump out the proton. Experimental observations are in accordance with the predicted relationship between growth, ATP dissipation and proton exchange. PMID- 26883121 TI - Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury. AB - BACKGROUND: Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. METHODS: Blood was sampled from 166 isolated TBI patients (aged 45 +/- 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1beta, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1beta, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (<=4) outcomes. RESULTS: Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF alpha, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL 1beta, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL 1beta, IL-10, TNF-alpha, eotaxin, IL-8, IP-10, and MCP-1. CONCLUSIONS: Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury. PMID- 26883126 TI - Am I My Brother's Keeper? Moral Dimensions of Informal Caregiving in a Neoliberal Society. AB - Within the current Dutch policy context the role of informal care is revalued. Formal care activities are reduced and family and friends are expected to fill this gap. Yet, there is little research on the moral ambivalences that informal care for loved ones who have severe and ongoing mental health problems entails, especially against the backdrop of neoliberal policies. Giving priority to one's own life project or caring for a loved one with severe problems is not reconciled easily. Using a case study we illustrate the moral ambivalences that persons may experience when they try to shape their involvement and commitment when a relative is in need. The case comes from a research project which explores whether it is possible to reduce coercive measures in psychiatry by organizing a Family Group Conference. The purpose of the article is to explore what theoretical concepts such as 'communities of fate', 'communities of choice' and 'personal communities' add in understanding how persons shape their involvement and commitment when a family member experiences recurrent psychiatric crises. PMID- 26883125 TI - Associations of food consumption, serum vitamins and metabolic syndrome risk with physical activity level in middle-aged adults: the National Health and Nutrition Examination Survey (NHANES) 2005-2006. AB - OBJECTIVE: To examine the associations of food consumption, serum vitamins and metabolic syndrome risk with physical activity level in middle-aged adults. DESIGN: Cross-sectional. SETTING: National Health and Nutrition Examination Survey (NHANES) 2005-2006. SUBJECTS: Adults aged 40-70 years were divided into three groups by tertile of accelerometer-determined steps/d (in men and women, respectively): tertile 1 (sedentary), <6802, <5785; tertile 2 (intermediate), 6802-10698, 5785-9225; tertile 3 (active), >=10699, >=9226. RESULTS: The active men consumed more grain products, fruits and vegetables, whereas the active women consumed more legumes and vegetables, compared with the sedentary group. Serum vitamin concentrations were associated with daily steps in both men and women. Vitamin C, alpha-carotene, trans-beta-carotene, cis-beta-carotene, beta cryptoxanthin, lutein+zeaxanthin, lycopene, gamma-tocopherol and vitamin D were significantly associated with daily steps. OR (P<0.05) for the sedentary group were 1.52 and 1.61 for low HDL cholesterol, 1.66 and 3.97 for hypertriacylglycerolaemia, 1.02 and 2.73 for abdominal obesity, 1.79 and 1.77 for hyperglycaemia, 1.59 and 1.60 for hypertension, and 1.85 and 2.47 for metabolic syndrome in men and women, respectively. CONCLUSIONS: Those with the highest steps taken showed a more healthful eating profile and a better serum vitamin profile compared with less active adults. Those with the lowest steps taken had greater odds of having metabolic syndrome and its risk components. Probably, daily walking is a marker of a healthful eating profile and increasing daily walking is one of the healthful ways to decrease the metabolic syndrome and its risk components. PMID- 26883128 TI - Heterotrophic Bioleaching of Sulfur, Iron, and Silicon Impurities from Coal by Fusarium oxysporum FE and Exophiala spinifera FM with Growing and Resting Cells. AB - Coal is the most abundant fossil fuel containing sulfur and other elements which promote environmental pollution after burning. Also the silicon impurities make the transportation of coal expensive. In this research, two isolated fungi from oil contaminated soil with accessory number KF554100 (Fusarium oxysporum FE) and KC925672 (Exophiala spinifera FM) were used for heterotrophic biological leaching of coal. The leaching were detected by FTIR, CHNS, XRF analyzer and compared with iron and sulfate released in the supernatant. The results showed that E. spinifera FM produced more acidic metabolites in growing cells, promoting the iron and sulfate ions removal while resting cells of F. oxysporum FE enhanced the removal of aromatic sulfur. XRF analysis showed that the resting cells of E. spinifera FM proceeded maximum leaching for iron and silicon (48.8, 43.2 %, respectively). CHNS analysis demonstrated that 34.21 % of sulfur leaching was due to the activities of resting cells of F. oxysporum FE. Also F. oxysporum FE removed organic sulfur more than E. spinifera FM in both growing and resting cells. FTIR data showed that both fungi had the ability to remove pyrite and quartz from coal. These data indicated that inoculations of these fungi to the coal are cheap and impurity removals were faster than autotrophic bacteria. Also due to the removal of dibenzothiophene, pyrite, and quartz, we speculated that they are excellent candidates for bioleaching of coal, oil, and gas. PMID- 26883127 TI - High-Efficiency, Two-Step Scarless-Markerless Genome Genetic Modification in Salmonella enterica. AB - We present a two-step method for scarless-markerless genome genetic modification in Salmonella enterica based on the improved suicide plasmid pGMB152. The whole LacZYA gene can provide a lacZ-based blue/white screening strategy for fast selection of double-crossover mutants by allelic exchange. The high efficiency of this genetic engineering strategy permits the study of gene function by gene knockin, site-directed mutagenesis, and gene knockout to construct live attenuated vaccines. PMID- 26883129 TI - Promoting Early, Safe Return to Work in Injured Employees: A Randomized Trial of a Supervisor Training Intervention in a Healthcare Setting. AB - Purpose Supervisors in the healthcare sector have the potential to contribute to disability prevention in injured employees. Published data on the evaluation of return to work (RTW) interventions aimed at direct supervisors are scarce. We sought to determine the effect of a brief audiovisual supervisor training module on supervisor RTW attitudes and knowledge. Methods A parallel-group study, using equal randomization, comparing the training module intervention to usual practice in healthcare supervisors at a quaternary care hospital was conducted. Differences between groups in changes in RTW attitude and knowledge survey question scores between baseline and 3 months were assessed using the Mann Whitney U test. The Benjamini-Hochberg-Yekutieli procedure was used to control for false discovery rate and generate adjusted p values. Results Forty supervisors were allocated to the intervention group and 41 to the usual practice group. Attitude and knowledge scores for most questions improved between baseline and immediately after intervention administration. Comparing intervention (n = 33) and usual practice groups (n = 37), there was a trend toward greater increase between baseline and 3 months follow-up in agreement that the supervisor can manage the RTW process (U = 515, adjusted p value = 0.074) and in confidence that the supervisor can answer employees' questions (U = 514, adjusted p value = 0.074) in the intervention group, although these findings were not statistically significant. Conclusions The training intervention may have provided the initial tools for supervisors to navigate the RTW process in collaboration with others in the RTW community of practice. A larger study with longer follow-up is needed to confirm results. PMID- 26883130 TI - Erratum to: Numerical Equilibrium Analysis for Structured Consumer Resource Models. PMID- 26883131 TI - Biogeographic Patterns Between Bacterial Phyllosphere Communities of the Southern Magnolia (Magnolia grandiflora) in a Small Forest. AB - The phyllosphere presents a unique system of discrete and easily replicable surfaces colonized primarily by bacteria. However, the biogeography of bacteria in the phyllosphere is little understood, especially at small to intermediate scales. Bacterial communities on the leaves of 91 southern magnolia (Magnolia grandiflora) trees 1-452 m apart in a small forest plot were analyzed and fragments of the 16S ribosomal RNA (rRNA) gene sequenced using the Illumina platform. Assemblages were dominated by members of the Alphaproteobacteria, Bacteroidetes, and Acidobacteria. Patterns in community composition were measured by both relative abundance (theta) and presence-absence (Jaccard) dissimilarity metrics. Distance-based Moran's eigenvector map analyses of the distance-decay relationship found a significant, positive relationship between each dissimilarity metric and significant eigenfunctions derived from geographic distance between trees, indicating trees that were closer together had more similar bacterial phyllosphere communities. Indirect gradient analyses revealed that several environmental parameters (canopy cover, tree elevation, and the slope and aspect of the ground beneath trees) were significantly related to multivariate ordination scores based on relative bacterial sequence abundances; however, these relationships were not significant when looking at the incidence of bacterial taxa. This suggests that bacterial growth and abundance in the phyllosphere is shaped by different assembly mechanisms than bacterial presence or absence. More broadly, this study demonstrates that the distance-decay relationship applies to phyllosphere communities at local scales, and that environmental parameters as well as neutral forces may both influence spatial patterns in the phyllosphere. PMID- 26883133 TI - Value of Comorbidity Scales for Predicting Survival After Radiochemotherapy of Small Cell Lung Cancer. AB - The Charlson Comorbidity Index plus three comorbidity scales were evaluated for survival after radiochemotherapy of limited stage SCLC. For the Charlson Comorbidity Index, 2-4 points were compared to 5-8 points. For the Age Comorbidity Score, 2-6 points were compared to 7-10 points. For the Medical Research Council (MRC) Breathlessness Scale, grades 0-2 were compared to grades 3 5. For the Simplified Comorbidity Score, 0-5 points were compared to 6-11 and 12 17 points. Charlson Comorbidity Index (p = 0.022) and MRC Breathlessness Scale (p < 0.001) showed significant associations with survival, the Age-Comorbidity Score a trend (p = 0.06). For the Simplified Comorbidity Score, no significant correlation was found (p = 0.54). Absolute differences in survival >=20 % were observed for the MRC Breathlessness Scale at 1, 2, and 3 years, for the Charlson Comorbidity Index at 1 year, and for the Age-Comorbidity Score at 2 years. Thus, particularly the MRC Breathlessness Scale can contribute to personalization of the treatment of SCLC. PMID- 26883132 TI - Cost Effectiveness of Paliperidone Long-Acting Injectable Versus Other Antipsychotics for the Maintenance Treatment of Schizophrenia in France. AB - BACKGROUND: French clinical recommendations suggest prescribing long-acting injectable (LAI) antipsychotics to patients with a maintenance treatment indication in schizophrenia. Despite this, and due to their relatively high acquisition and administration costs, LAIs are still underused in clinical practice in France, thus highlighting the need for pharmacoeconomic evaluations. OBJECTIVE: Our objective was to estimate the cost effectiveness of paliperidone LAI (or paliperidone palmitate), a once-monthly second-generation LAI antipsychotic, compared with the most common antipsychotic medications for the maintenance treatment of schizophrenia in France. METHODS: A Markov model was developed to simulate the progression of a cohort of schizophrenic patients through four health states (stable treated, stable non-treated, relapse and death) and to consider up to three lines of treatment to account for changes in treatment management. Paliperidone LAI was compared with risperidone LAI, aripiprazole LAI, olanzapine LAI, haloperidol LAI (or haloperidol decanoate) and oral olanzapine. Costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over 5 years based on 3-month cycles with a discount rate of 4% and from a French health insurance perspective. Patients were considered to be stabilised after a schizophrenic episode and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on real-life French data to capture adherence effects. Safety and utility data were derived from international publications. Additionally, costs were retrieved from French health insurance databases and publications. Finally, expert opinion was used for validation purposes or in case of gaps in data. The robustness of results was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: All LAI antipsychotics were found to have similar costs over 5 years: approximatively ?55,000, except for paliperidone LAI which had a discounted cost of ?50,880. Oral olanzapine was less costly than LAIs (i.e. ?50,379 after 5 years) but was associated with fewer QALYs gained and relapses avoided. Paliperidone LAI dominated aripiprazole LAI, olanzapine LAI and haloperidol LAI in terms of costs per QALY, and it was associated with slightly fewer QALYs when compared with risperidone LAI (i.e. 3.763 vs 3.764). This resulted in a high incremental cost effectiveness ratio (ICER) (i.e. ?4,770,018 per QALY gained) for risperidone LAI compared with paliperidone LAI. Paliperidone LAI was more costly than olanzapine oral but associated with more QALYs (i.e. ICER of ?2411 per QALY gained for paliperidone LAI compared with oral olanzapine). Paliperidone LAI had a probability of being the optimal strategy in more than 50% of cases for a willingness-to-pay threshold of ?8000 per QALY gained. CONCLUSION: This analysis, to the best of our knowledge, is the first of its kind to assess the cost effectiveness of antipsychotics based on French observational data. Paliperidone LAI appeared to be a cost-effective option in the treatment of schizophrenia from the French health insurance perspective. PMID- 26883134 TI - Association Between Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria in Children with Cerebral Palsy. AB - PURPOSE: Children with cerebral palsy (CP) are at an increased risk for aspiration, and subsequent pneumonia or pneumonitis. Pneumonia is a common cause of hospital admission, intensive care unit (ICU) admission, and death in patients with CP, and may disproportionately contribute to mortality. The role of respiratory microflora is unknown. This study examined the relationship between respiratory infections with Gram-negative bacteria (GNB), particularly Pseudomonas aeruginosa, and the frequency/severity of pneumonia hospitalization. METHODS: Retrospective chart review of 69 patients with CP and hospitalization for pneumonia. Eligible patients required hospitalization for bacterial pneumonia, at least one respiratory culture, and fulfillment of Bax definition of CP. Group assignment was based on respiratory culture. Charts were analyzed for comorbid illness, hospitalization demographics, and disease severity. RESULTS: Children with isolation of P. aeruginosa or other GNB had increased frequency of ICU admission (77.4, 65.1, vs. 26.9 %, respectively, p < 0.01), intubation (45.2, 39.5 vs. 11.5 %, p = 0.02, p = 0.03 respectively), and large pleural effusions (37.5, vs. 0 %) than children without GNB. Children with isolation of GNB had more prolonged hospitalizations and were more likely to have multiple hospitalizations than those without GNB. CONCLUSION: Colonization with P. aeruginosa and other Gram-negative organisms in children with CP is associated with increased morbidity, prolonged hospitalization, and severity of pneumonia including need for PICU admission and intervention. Further research is required to determine causality, the role of antimicrobials active against Gram negative in pneumonia treatment, and the role of GNB eradication therapy in children with CP. PMID- 26883135 TI - Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework. AB - BACKGROUND: Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. OBJECTIVE: The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. METHODS: The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. RESULTS: The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. CONCLUSIONS: The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate their effectiveness across multiple implementation settings and chronic diseases. PMID- 26883136 TI - Old and outdated radiology equipment in Croatia-radiation safety and economic consequences. PMID- 26883137 TI - Imaging findings of splenic emergencies: a pictorial review. AB - Although traumatic injuries are the cause of common splenic emergencies in the emergency room, various nontraumatic conditions may also affect the spleen with possible life-threatening results. In this pictorial review, we present imaging findings of usual and unusual splenic emergencies. It is essential to be familiar with key imaging findings and advantages of different modalities to reach a definitive diagnosis. TEACHING POINTS: * Delayed splenic rupture is commonly related to subcapsular hematoma. * Subtle haemorrhage is commonly restricted to the site of injury "sentinel clot sign". * The whorled appearance is the key imaging feature of splenic torsion. PMID- 26883138 TI - How to diagnose acute appendicitis: ultrasound first. AB - Acute appendicitis (AA) is a common abdominal emergency with a lifetime prevalence of about 7 %. As the clinical diagnosis of AA remains a challenge to emergency physicians and surgeons, imaging modalities have gained major importance in the diagnostic work-up of patients with suspected AA in order to keep both the negative appendectomy rate and the perforation rate low. Introduced in 1986, graded-compression ultrasound (US) has well-established direct and indirect signs for diagnosing AA. In our opinion, US should be the first-line imaging modality, as graded-compression US has excellent specificity both in the paediatric and adult patient populations. As US sensitivity is limited, and non diagnostic US examinations with non-visualization of the appendix are more a rule than an exception, diagnostic strategies and algorithms after non-diagnostic US should focus on clinical reassessment and complementary imaging with MRI/CT if indicated. Accordingly, both ionizing radiation to our patients and cost of pre therapeutic diagnosis of AA will be low, with low negative appendectomy and perforation rates. Main Messages * Ultrasound (US) should be the first imaging modality for diagnosing acute appendicitis (AA). * Primary US for AA diagnosis will decrease ionizing radiation and cost. * Sensitivity of US to diagnose AA is lower than of CT/MRI. * Non-visualization of the appendix should lead to clinical reassessment. * Complementary MRI or CT may be performed if diagnosis remains unclear. PMID- 26883139 TI - Reporting knee meniscal tears: technical aspects, typical pitfalls and how to avoid them. AB - Magnetic resonance imaging (MRI) is the most accurate imaging technique in the diagnosis of meniscal lesions and represents a standard tool in knee evaluation. MRI plays a critical role in influencing the treatment decision and enables information that would obviate unnecessary surgery including diagnostic arthroscopy. An accurate interpretation of the knee depends on several factors, starting with technical aspects including radiofrequency coils, imaging protocol and magnetic field strength. The use of dedicated high-resolution orthopaedic coils with a different number of integrated elements is mandatory in order to ensure high homogeneity of the signal and high-resolution images. The clinical imaging protocol of the knee includes different MRI sequences with high-spatial resolution in all orientations: sagittal, coronal, and axial. Usually, the slice thickness is 3 mm or less, even with standard two-dimensional fast spin echo sequences. A common potential reason for pitfalls and errors of interpretation is the unawareness of the normal tibial attachments and capsular attachment of the menisci. Complete description of meniscal tears implies that the radiologist should be aware of the patterns and the complex classification of the lesions. TEACHING POINTS: * Technical factors may influence MRI interpretation. * Unawareness of the normal meniscal anatomy may lead to errors of interpretation. * Description of meniscal tears implies the knowledge of meniscal tear classification. PMID- 26883140 TI - Phenotypic and genotypic approach to characterize Arcanobacterium pluranimalium isolated from bovine milk samples. AB - In the present study, three Arcanobacterium pluranimalium strains isolated from bovine milk samples of three cows of three farms (two cows with subclinical mastitis) could successfully be identified by phenotypical investigations, by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis and genotypically by sequencing the molecular targets 16S rDNA, 16S-23S rDNA intergenic spacer region (ISR), the beta subunit of bacterial RNA polymerase encoding gene rpoB, the glyceraldehyde 3-phosphate dehydrogenase encoding gene gap, the elongation factor tu encoding gene tuf, and the pluranimaliumlysin encoding gene pla. The latter could also be identified by a loop-mediated isothermal amplification (LAMP) assay. The presented phenotypic and genotypic approaches might support the identification of A. pluranimalium in future and might help to understand the role this species plays in bovine mastitis. PMID- 26883141 TI - A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes. AB - OBJECTIVES: A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS: Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS: Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS: In women with surgically treated early stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen. PMID- 26883142 TI - Differences in the composition of arbuscular mycorrhizal fungal communities promoted by different propagule forms from a Mediterranean shrubland. AB - As it is well known, arbuscular mycorrhizal (AM) colonization can be initiated from the following three types of fungal propagules: spores, extraradical mycelium (ERM), and mycorrhizal root fragments harboring intraradical fungal structures. It has been shown that biomass allocation of AM fungi (AMF) among these three propagule types varies between fungal taxa, as also differs the ability of the different AMF propagule fractions to initiate new colonizations. In this study, the composition of the AMF community in the roots of rosemary (Rosmarinus officinalis L., a characteristic Mediterranean shrub), inoculated with the three different propagule types, was analyzed. Accordingly, cuttings from this species were inoculated with either AMF spores, ERM, or colonized roots extracted from a natural soil. The AMF diversity within the rosemary roots was characterized using terminal restriction fragment length polymorphism (T-RFLP) of the small subunit (SSU) rDNA region. The AMF community established in the rosemary plants was significantly different according to the type of propagule used as inoculum. AMF taxa differed in their ability to initiate new colonizations from each propagule type. Results suggest different colonization strategies for the different AMF families involved, Glomeraceae and Claroideoglomeraceae colonizing mainly from colonized roots whereas Pacisporaceae and Diversisporaceae from spores and ERM. This supports that AMF taxa show contrasting life-history strategies in terms of their ability to initiate new colonizations from the different propagule types. Further research to fully understand the colonization and dispersal abilities of AMF is essential for their rational use in ecosystem restoration programs. PMID- 26883145 TI - The explosion of percutaneous mitral valve therapies. PMID- 26883146 TI - Oxidative stress during bacterial growth characterized through microdialysis sampling coupled with HPLC/fluorescence detection of malondialdehyde. AB - Organisms that grow aerobically are routinely exposed to oxidative stress in the form of reactive oxygen species. Monitoring the dynamic variations of oxidative stress allows us to understand its role in basic cellular function and determine mechanisms of antioxidation. In this study, microdialysis (MD) sampling was employed for continuous monitoring of the formation of malondialdehyde (MDA) in a bacterium-inoculated culture broth. To test the practicality of this approach, oxidative stress was induced by cadmium and then a 60-min interval was selected to collect sufficient amounts of dialysate for high-performance liquid chromatography with fluorescence (HPLC-FL) detection. After optimization of this simple-to-operate, simultaneous, and continuous method for dynamic monitoring of MDA during periods of bacterial growth, a retrodialysis technique and a no-net flux method were used to assess the probe recovery and analytical performance of the proposed system. The mean probe recovery of MDA was 78.6 +/- 0.9%, with intra and interday precisions of 2.7-6.1 and 3.5-7.6%, respectively. To evaluate the practicality of this method, the dynamic variations in the concentrations of MDA in standardized bacterial species (Staphylococcus aureus, ATCC((r)) 29213TM) were monitored continuously for 24h. The analytical results confirmed that this MD sampling technique combined with HPLC-FL detection can be used to accurately and continuously monitor the levels of MDA in microbially inoculated culture broths. PMID- 26883144 TI - Hematopoietic stem cells: multiparameter regulation. AB - Hematopoietic stem cells (HSCs) are capable to self-renew with multi-potency which generated much excitement in clinical therapy. However, the main obstacle of HSCs in clinical application was insufficient number of HSCs which were derived from either bone marrow, peripheral blood or umbilical cord blood. This review briefly discusses the indispensable utility of growth factors and cytokines, stromal cells, extracellular matrix, bionic scaffold and microenvironment aiming to control the hematopoiesis in all directions and provide a better and comprehensive understanding for in vitro expansion of hematopoietic stem cells. PMID- 26883143 TI - Functional near-infrared spectroscopy for neuroimaging in cochlear implant recipients. AB - Functional neuroimaging can provide insight into the neurobiological factors that contribute to the variations in individual hearing outcomes following cochlear implantation. To date, measuring neural activity within the auditory cortex of cochlear implant (CI) recipients has been challenging, primarily because the use of traditional neuroimaging techniques is limited in people with CIs. Functional near-infrared spectroscopy (fNIRS) is an emerging technology that offers benefits in this population because it is non-invasive, compatible with CI devices, and not subject to electrical artifacts. However, there are important considerations to be made when using fNIRS to maximize the signal to noise ratio and to best identify meaningful cortical responses. This review considers these issues, the current data, and future directions for using fNIRS as a clinical application in individuals with CIs. This article is part of a Special Issue entitled . PMID- 26883148 TI - Neuroprotective oleanane triterpenes from the roots of Bupleurum chinense. AB - The discovery of new natural compounds with pharmacological properties is an increasingly important field, and a continuous phytochemical investigation of the roots of Bupleurum chinense D.C. has led to the isolation of 17 triterpenoids, including three new oleanane triterpenes (1-3) together with 14 known ones. Their structures were determined on the basis of 1D and 2D NMR spectra as well as HR ESI-MS data. The cytotoxicities of all compounds against five selected human cancer cell lines were assayed. Only compounds 9 and 14 exhibited moderate activities. Recently, a number of investigations have focused on the neuroprotective properties of triterpenoids in B. chinense. In order to expand our knowledge about this herb, the neuroprotective effects of compounds 1-17 against hydrogen peroxide (H2O2)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells were evaluated. Compounds 1-3, 6-7 showed significant neuroprotective effects against H2O2-induced SH-SY5Y cell death. Preliminary structure-activity relationships (SARs) between neuroprotective effects and the isolates were also discussed. PMID- 26883147 TI - Captopril analogues as metallo-beta-lactamase inhibitors. AB - A number of captopril analogues were synthesised and tested as inhibitors of the metallo-beta-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid. PMID- 26883149 TI - Identification of human telomerase inhibitors having the core of N-acyl-4,5 dihydropyrazole with anticancer effects. AB - Eight human telomerase inhibitors (5a-5h) having the core of N-acyl-4,5 dihydropyrazole with anticancer effects were identified in this study. Biological results revealed that a few compounds had potent anticancer activities against three common tumor cell lines (SGC-7901, HepG2 and MGC-803). Among them, compound 5c, with a molecular weight of only 272.2 Da, had antiproliferative activities against SGC-7901 and MGC-803 with EC50 values of 2.06 +/- 0.17 and 2.89 +/- 0.62 MUM, respectively, better than 5-Fluorouracil. Compound 5c inhibited the enzyme of telomerase with an IC50 value of 1.86 +/- 0.51 MUM, surpassing the control compound, ethidium bromide. Modeling study showed that this compound can reside in the binding pocket of the telomerase/TNA:DNA hairpin complex. When the moiety of N-acyl was changed to N-sulfonyl, the gotten compounds (8a-8i) had deteriorative activities against both these three cancer cell lines and the enzyme of telomerase. PMID- 26883150 TI - Isatin derivatives with activity against apoptosis-resistant cancer cells. AB - In a search of small molecules active against apoptosis-resistant cancer cells, a series of isatin-based heterocyclic compounds were synthesized and found to inhibit proliferation of cancer cell lines resistant to apoptosis. The synthesis of these compounds involved a condensation of commercially available, active methylene heterocycles with isatin proceeding in moderate to excellent yields. The heterocyclic scaffolds prepared in the current investigation appear to be a useful starting point for the development of agents to fight cancers with apoptosis resistance, and thus, associated with dismal prognoses. PMID- 26883151 TI - Renal Tumors in 26-Week Tg.Rash2 Mice Carcinogenicity Studies. AB - We report renal tubular adenomas and a carcinoma in 26-week Tg.rasH2 mouse carcinogenicity studies, which have not been reported to date either at our facility or in other published data. However, during the year 2014, renal tubular tumors were present in 4 studies conducted at our facility. Because of their morphological similarity to the amphophilic-vacuolar (AV) phenotypic variant of renal tubule tumors noted in Sprague-Dawley and Fischer 344 rats, which are thought to be familial, as well as the genetic homogeneity of Tg.rasH2 mice, we tracked the parents of these mice with tumors in each study. The origin of these tumors could not be traced back to any of the parents or even an animal barrier, and these tumors were not attributed to the vehicle or test article. Although the exact mechanism of tumorigenesis was not known, based on the available information, the development of renal tumors in these mice was considered random and spontaneous. PMID- 26883152 TI - Tissue Sampling Guides for Porcine Biomedical Models. AB - This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ~50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitative analyses, including cryohistology, paraffin, and plastic histology; immunohistochemistry;in situhybridization; electron microscopy; and quantitative stereology as well as molecular analyses of DNA, RNA, proteins, metabolites, and electrolytes. With regard to the planned extent of sampling efforts, time, and personnel expenses, and dependent upon the scheduled analyses, different protocols are provided. These protocols are adjusted for (I) routine screenings, as used in general toxicity studies or in analyses of gene expression patterns or histopathological organ alterations, (II) advanced analyses of single organs/tissues, and (III) large-scale sampling procedures to be applied in biobank projects. Providing a robust reference for studies of porcine models, the described protocols will ensure the efficiency of sampling, the systematic recovery of high-quality samples representing the entire organ or tissue as well as the intra-/interstudy comparability and reproducibility of results. PMID- 26883153 TI - Swine in Translational Research and Drug Development. PMID- 26883154 TI - Sexual Maturation in the Female Gottingen Minipig. AB - In the literature, experimental data on sexual maturation of female Gottingen minipigs are lacking. This may impede a reliable evaluation of reproductive functioning, particularly in the young (immature) sow used in toxicity studies. To find suitable method(s) to detect ovulation during in-life, a pilot study was performed with 3 adult sows (approximately 10-11 months), followed by a study with 14 immature females (approximately 3-4 months). From the tested parameters, progesterone analysis was the most reliable predictor. First progesterone peaks were observed in 13 sows at 3.7-4.2 or 5.5-6.5 months with a cycle length of 17 22 days. One sow did not show progesterone release until necropsy at 7 months of age. Histopathology of the reproductive organs confirmed sexual maturity for all sows, except the one without progesterone peak. In conclusion, the age range of sexual maturity of female Gottingen minipigs (3.7-6.5 months) is much wider than previously thought, and in-life progesterone analysis is a useful tool to determine sexual maturity of individual animals. PMID- 26883155 TI - A Translational Model for Diet-related Atherosclerosis: Effect of Statins on Hypercholesterolemia and Atherosclerosis in a Minipig. AB - Models of atherosclerosis are used in preclinical studies but often fail to translate to humans. A model that better reflects human atherosclerosis is necessary. We recently engineered the ExeGenTM low-density lipoprotein receptor (LDLR) miniswine, in which the LDL receptor gene is modified to drive hypercholesterolemia and atherosclerosis, and showed diet-related exacerbation of these phenotypes. Five groups of animals, either wild type (+/+) or heterozygous (+/-), were fed either a normal or high-fat diet for 6 months. One group of heterozygous pigs fed a high-fat diet was also administered atorvastatin at 3 mg/kg/day. Clinical chemistry and anatomic pathology parameters were measured biweekly and at termination. The high-fat diet resulted in increased adiposity and interspersion of adipocytes within the salivary glands. The heterozygous pigs on the high-fat diet gained more weight and had significant increases in total cholesterol, high-density lipoprotein, and LDL compared to wild-type animals or heterozygous animals fed a normal diet. Atorvastatin attenuated these parameters, indicating the statin had a beneficial effect, even in a high-fat diet scenario. Atorvastatin treatment also reduced the intensity of Oil Red O staining in pigs on high-fat diet. Atorvastatin-related amelioration of several indices of cardiovascular pathophysiology in this model underscores its utility for drug discovery. PMID- 26883156 TI - In Reply: Tranexamic Acid Benefits Total Joint Arthroplasty Patients Regardless of Preoperative Hemoglobin Value. PMID- 26883157 TI - Radiation Exposure During Fluoro-Assisted Direct Anterior Total Hip Arthroplasty. AB - BACKGROUND: Utilization of the direct anterior approach (DAA) for total hip arthroplasty (THA) has increased in the last decade with fluoroscopy often used to confirm implant position, leg length, and offset. Radiation exposure thresholds around 800 mGy are published for the risk of cataracts. We hypothesized that surgeon eye exposure during fluoro-assisted DAA total hip arthroplasty would be well below these published thresholds. METHODS: Three experienced orthopedic surgeons performed 30 consecutive fluoro-assisted DAA THAs. During each procedure, the surgeon wore a helmet-mounted dosimeter. After 30 consecutive cases, the dosimeters were analyzed. A chart review was then completed to obtain fluoroscopic data saved for each individual case including fluoroscopic time, total radiation dose, and radiation tech experience. RESULTS: Fluoroscopic data were available for 89 of 90 cases (98.8%). Surgeon 1 had an average fluoroscopic time of 18.51 seconds, radiation dose of 2.396 mGy, and tech experience of 13.06 years. Surgeon 2 had an average fluoroscopic time of 15.63 seconds, radiation dose of 2.139 mGy, and tech experience of 23.69 years. Surgeon 3 had an average fluoroscopic time of 11.06 seconds, radiation dose of 1.462 mGy, and tech experience of 16.03 years. The dosimeter results were 8, 5, and <1 mrem, respectively, for each surgeon. The mean total radiation dose per case for all surgeons was 2.00 mGy (+/-1.31), and there was no correlation between radiation dose and radiologic tech experience (0.089, P > .05) or radiation dose and patients' body mass index (0.260, P = .014). CONCLUSIONS: Each surgeon would need to perform >300,000 DAA THAs to exceed the 800-mGy cataract threshold dose. The decision to wear protective glasses should be at the surgeon's discretion; however, the findings in this study show a very low radiation dose to the surgeon's eye regardless of radiologic tech experience or patient's body mass index. PMID- 26883158 TI - Conversion of a Surgically Arthrodesed Knee to a Total Knee Arthroplasty-Is it Worth it? A Meta-Analysis. AB - BACKGROUND: Conversion of a surgically arthrodesed knee to total knee arthroplasty (TKA) is an option for a select group of patients who are not satisfied with their results. However, there is a paucity of literature on this topic. A systematic review of literature was performed to (1) describe the overall demographic characteristics; (2) evaluate the clinical outcomes; (3) determine the overall rate of complications; and (4) evaluate the overall satisfaction of patients who underwent conversion of an arthrodesed knee to TKA. METHODS: A comprehensive literature search was systematically performed to evaluate all studies included in the literature until July 2015. The specific search terms used were "fusion knee" and "arthrodesis knee," which revealed a total of 2206 studies. A review and selection of these abstracts were then performed based on inclusion and/or exclusion criteria; a total of 10 articles were used for final review. RESULTS: There were a total of 98 surgically arthrodesed knees that subsequently underwent TKA. Patients had a mean age of 55 years and were followed up for a mean of 5 years. Using a random effects model, there was an overall complication rate of 47%, an overall revision rate of 25%, and an overall failure rate of 11%. However, most patients were overall satisfied with the procedure. CONCLUSION: Fusion takedown is a challenging procedure that should only be performed by experienced surgeons after extensive discussion with the patients. The clinical outcomes are good with overall patient satisfaction, but complication rates are high including risk of repeat fusion or amputation. PMID- 26883159 TI - Interaction of EGFR to delta-catenin leads to delta-catenin phosphorylation and enhances EGFR signaling. AB - Expression of delta-catenin reportedly increases during late stage prostate cancer. Furthermore, it has been demonstrated that expression of EGFR is enhanced in hormone refractory prostate cancer. In this study, we investigated the possible correlation between EGFR and delta-catenin in prostate cancer cells. We found that EGFR interacted with delta-catenin and the interaction decreased in the presence of EGF. We also demonstrated that, on one hand, EGFR phosphorylated delta-catenin in a Src independent manner in the presence of EGF and on the other hand, delta-catenin enhanced protein stability of EGFR and strengthened the EGFR/Erk1/2 signaling pathway. Our findings added a new perspective to the interaction of EGFR to the E-cadherin complex. They also provided novel insights to the roles of delta-catenin in prostate cancer cells. PMID- 26883160 TI - Top-down control of arousal and sleep: Fundamentals and clinical implications. AB - Mammalian sleep emerges from attenuated activity in the ascending reticular arousal system (ARAS), the main arousal network of the brain. This system originates in the brainstem and activates the thalamus and cortex during wakefulness via a well-characterized 'bottom-up' pathway. Recent studies propose that a less investigated cortico-thalamic 'top-down' pathway also regulates sleep. The present work integrates the current evidence on sleep regulation with a focus on the 'top-down' pathway and explores the potential to translate this information into clinically relevant interventions. Specifically, we elaborate the concept that arousal and sleep continuity in humans can be modulated by non invasive brain stimulation (NIBS) techniques that increase or decrease cortical excitability. Based on preclinical studies, the modulatory effects of the stimulation are thought to extend to subcortical arousal networks. Further exploration of the 'top-down' regulation of sleep and its modulation through non invasive brain stimulation techniques may contribute to the development of novel treatments for clinical conditions of disrupted arousal and sleep, which are among the major health problems worldwide. PMID- 26883162 TI - Surgicopathologic correlations regarding lymphatics in hilar cholangiocarcinoma. PMID- 26883161 TI - Sleep propensity in psychiatric hypersomnolence: A systematic review and meta analysis of multiple sleep latency test findings. AB - Hypersomnolence plays a sizeable role in the course and morbidity of psychiatric disorders. Current sleep medicine nosology is reliant on the multiple sleep latency test (MSLT) to segregate hypersomnolence associated with psychiatric disorders from other central nervous system causes. However, the evidence base regarding sleep propensity in psychiatric hypersomnolence as measured by the MSLT has not been systematically evaluated, which is vital to clarify the utility and validity of current nosological schema. In this review, the use of sleep propensity assessed by the MSLT in patients with psychiatric hypersomnolence is systematically evaluated, using both qualitative and quantitative assessment. Findings demonstrate high heterogeneity and potential for bias among studies, with a pooled estimate of sleep propensity among patients with psychiatric hypersomnolence similar to normative values. Additionally, approximately 25% of patients with psychiatric hypersomnolence demonstrate a mean sleep latency below 8 min, the current cutpoint to define pathologic sleepiness. These data underscore the limitations of the MSLT in segregating psychiatric hypersomnolence from other central nervous system hypersomnias. Further research is warranted to evaluate novel measures and biomarkers of excessive sleepiness to advance clinical practice, as well as dimensional approaches to classification of hypersomnolence disorders. PMID- 26883163 TI - Perioperative mortality: Analysis of 3 years of operative data across 7 general surgical projects of Medecins Sans Frontieres in Democratic Republic of Congo, Central African Republic, and South Sudan. AB - BACKGROUND: The African continent has the greatest burden of surgical disability adjusted life years, yet the least is known about operative care here. This analysis describes the surgical patients admitted to 7 hospitals supported by the Medecins Sans Frontieres (MSF) over 3 years in 3 conflict-affected countries Eastern Democratic Republic of Congo, Central African Republic, and South Sudan. METHODS: A standardized operative data collection tool was used for routine collection of operative inpatient data between 2011 and 2013 at 7 MSF surgical facilities. Surgical records of 14,482 patients were analyzed to describe surgical epidemiology, major procedures, and perioperative mortality. The perioperative mortality rate (POMR) was calculated within 2 days of admission (POMR2) and within 30 days from admission (POMR30). The POMR is used as a marker of quality of operative care. RESULTS: Caesarean delivery was the most common major procedure performed and had a POMR30 of 5.28 per 1,000 admissions. The overall inpatient mortality was 19.67 per 1,000 admissions. Children had greater POMR than adults for the same procedure types (47.97 vs 15.89 deaths per 1,000 admissions, P < .001); 85.1% of all major procedures were emergency procedures and between 3 and 30% of admissions were related to violence. After adjustment, perioperative death was associated with emergency surgery, violence, and age younger than 15 years. CONCLUSION: POMRs varied by age group and type of major procedure performed. Collecting surgical data is achievable and can inform future planning and support for national surgical programs. More information is needed on operative outcomes in adults and children in low-resource settings to improve quality and access to care. PMID- 26883164 TI - Luminescent platinum(II) complexes with functionalized N-heterocyclic carbene or diphosphine selectively probe mismatched and abasic DNA. AB - The selective targeting of mismatched DNA overexpressed in cancer cells is an appealing strategy in designing cancer diagnosis and therapy protocols. Few luminescent probes that specifically detect intracellular mismatched DNA have been reported. Here we used Pt(II) complexes with luminescence sensitive to subtle changes in the local environment and report several Pt(II) complexes that selectively bind to and identify DNA mismatches. We evaluated the complexes' DNA binding characteristics by ultraviolet/visible absorption titration, isothermal titration calorimetry, nuclear magnetic resonance and quantum mechanics/molecular mechanics calculations. These Pt(II) complexes show up to 15-fold higher emission intensities upon binding to mismatched DNA over matched DNA and can be utilized for both detecting DNA abasic sites and identifying cancer cells and human tissue samples with different levels of mismatch repair. Our work highlights the potential of luminescent Pt(II) complexes to differentiate between normal cells and cancer cells which generally possess more aberrant DNA structures. PMID- 26883166 TI - Reference values for time- and frequency-domain heart rate variability measures. AB - BACKGROUND: The analysis of heart rate variability (HRV) has become an established procedure in recent decades. Because there are no appropriate reference values available, HRV findings can still only be compared within a group or in individuals in longitudinal studies. OBJECTIVE: The objectives of the present study were to examine a group of healthy subjects of different ages and sexes and to identify reference values for common HRV parameters. METHODS: Long term 24-hour electrocardiograms of 695 voluntary subjects were recorded by using a 2-channel Holter system over a period of 24 hours during daily activities. RESULTS: Reference values for men and women in 10-year age groups were calculated for standard deviation of NN intervals, root mean square of successive differences of NN intervals, standard deviation of the average of all consecutive 5-minute NN intervals, percentage of consecutive NN intervals that deviate from one another by more than 50 ms, low-frequency power normalized unit, high frequency power normalized unit, low frequency/high frequency ratio, SD1, and SD2. The 5th and 95th percentiles were given for each sex and for the age groups 20-30, 30-40, 40-50, and 50-60 years. We observed a consistent decrease in HRV measures with increasing age as well as a sex dependency of HRV findings. CONCLUSION: We studied a large group of healthy subjects and identified reference values for commonly used HRV measures for 24-hour ECG measurements. The reference values differed considerably from the values published in 1996 in the Guidelines of the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. In the future, steps should be taken to expand the database and define reference values for the age groups under 20 and over 60 years. It would be desirable to obtain reference values for short-term recordings (eg, 5-minute recordings) as well. PMID- 26883168 TI - Frailty Assessment in Advanced Heart Failure. AB - BACKGROUND: Several studies have recently demonstrated the value of frailty assessment in a general heart failure (HF) population; however, it is unknown whether these findings are also applicable in advanced HF. We investigated the utility of frailty assessment and its prognostic value in elderly patients with advanced HF. METHODS: Forty consecutive elderly subjects aged >=65 years, with left ventricular ejection fraction <=35%, New York Heart Association class III or IV, and a 6-minute walk test <300 m were enrolled from the HF clinic at Montefiore Medical Center between October 2012 and July 2013. Subjects were assessed for frailty with the Fried Frailty Index, consisting of 5 components: hand grip strength, 15-foot walk time, weight loss, physical activity, and exhaustion. All subjects were prospectively followed for death or hospitalization. RESULTS: At baseline, the mean age of the cohort was 74.9 +/- 6.5 years, 58% female, left ventricular ejection fraction 25.6 +/- 6.4%, 6-minute walk test 195.8 +/- 74.3 m and length of follow-up 454 +/- 186 days. Thirty-five percent were prefrail and 65% were frail. Frailty status was associated with the combined primary endpoint of mortality and all-cause hospitalization (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.15-3.25, P = .013). On individual analysis, frailty was associated with all-cause hospitalizations (HR 1.92, 95% CI 1.12-3.27, P = .017) and non-HF hospitalizations (HR 3.31, 95% CI 1.14- 9.6, P = .028), but was not associated with HF hospitalizations alone (HR 1.31, 95% CI 0.68-2.49, P = .380). CONCLUSIONS: Frailty assessment in patients with advanced HF is feasible and provides prognostic value. These findings warrant validation in a larger cohort. PMID- 26883167 TI - Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis. AB - Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N methyltransferase (PEMT) is a risk for the lean NASH. The Pemt-/- mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt /- mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4alpha resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities. PMID- 26883169 TI - SPECT/CT Imaging of Pluronic Nanocarriers with Varying Poly(ethylene oxide) Block Length and Aggregation State. AB - Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of (111)In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines. PMID- 26883170 TI - Self-organization of network dynamics into local quantized states. AB - Self-organization and pattern formation in network-organized systems emerges from the collective activation and interaction of many interconnected units. A striking feature of these non-equilibrium structures is that they are often localized and robust: only a small subset of the nodes, or cell assembly, is activated. Understanding the role of cell assemblies as basic functional units in neural networks and socio-technical systems emerges as a fundamental challenge in network theory. A key open question is how these elementary building blocks emerge, and how they operate, linking structure and function in complex networks. Here we show that a network analogue of the Swift-Hohenberg continuum model-a minimal-ingredients model of nodal activation and interaction within a complex network-is able to produce a complex suite of localized patterns. Hence, the spontaneous formation of robust operational cell assemblies in complex networks can be explained as the result of self-organization, even in the absence of synaptic reinforcements. PMID- 26883165 TI - Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress. AB - Mitochondria are important for providing cellular energy ATP through the oxidative phosphorylation pathway. They are also critical in regulating many cellular functions including the fatty acid oxidation, the metabolism of glutamate and urea, the anti-oxidant defense, and the apoptosis pathway. Mitochondria are an important source of reactive oxygen species leaked from the electron transport chain while they are susceptible to oxidative damage, leading to mitochondrial dysfunction and tissue injury. In fact, impaired mitochondrial function is commonly observed in many types of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, alcoholic dementia, brain ischemia-reperfusion related injury, and others, although many of these neurological disorders have unique etiological factors. Mitochondrial dysfunction under many pathological conditions is likely to be promoted by increased nitroxidative stress, which can stimulate post translational modifications (PTMs) of mitochondrial proteins and/or oxidative damage to mitochondrial DNA and lipids. Furthermore, recent studies have demonstrated that various antioxidants, including naturally occurring flavonoids and polyphenols as well as synthetic compounds, can block the formation of reactive oxygen and/or nitrogen species, and thus ultimately prevent the PTMs of many proteins with improved disease conditions. Therefore, the present review is aimed to describe the recent research developments in the molecular mechanisms for mitochondrial dysfunction and tissue injury in neurodegenerative diseases and discuss translational research opportunities. PMID- 26883171 TI - Structural analysis of disease-related TDP-43 D169G mutation: linking enhanced stability and caspase cleavage efficiency to protein accumulation. AB - The RNA-binding protein TDP-43 forms intracellular inclusions in amyotrophic lateral sclerosis (ALS). While TDP-43 mutations have been identified in ALS patients, how these mutations are linked to ALS remains unclear. Here we examined the biophysical properties of six ALS-linked TDP-43 mutants and found that one of the mutants, D169G, had higher thermal stability than wild-type TDP-43 and that it was cleaved by caspase 3 more efficiently, producing increased levels of the C terminal 35 kD fragments (TDP-35) in vitro and in neuroblastoma cells. The crystal structure of the TDP-43 RRM1 domain containing the D169G mutation in complex with DNA along with molecular dynamics simulations reveal that the D169G mutation induces a local conformational change in a beta turn and increases the hydrophobic interactions in the RRM1 core, thus enhancing the thermal stability of the RRM1 domain. Our results provide the first crystal structure of TDP-43 containing a disease-linked D169G mutation and a disease-related mechanism showing that D169G mutant is more susceptible to proteolytic cleavage by caspase 3 into the pathogenic C-terminal 35-kD fragments due to its increased stability in the RRM1 domain. Modulation of TDP-43 stability and caspase cleavage efficiency could present an avenue for prevention and treatment of TDP-43-linked neurodegeneration. PMID- 26883172 TI - Correction to Sargaquinoic Acid Inhibits TNF-alpha-Induced NF-kappaB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs). PMID- 26883173 TI - Reduced Graphene Oxide Thin Film on Conductive Substrates by Bipolar Electrochemistry. AB - Recent years have shown an increased interest in developing manufacturing processes for graphene and its derivatives that consider the environmental impact and large scale cost-effectiveness. However, today's most commonly used synthesis routes still suffer from their excessive use of harsh chemicals and/or the complexity and financial cost of the process. Furthermore, the subsequent transfer of the material onto a substrate makes the overall process even more intricate and time-consuming. Here we describe a single-step, single-cell preparation procedure of metal-supported reduced graphene oxide (rGO) using the principle of bipolar electrochemistry of graphite in deionized water. Under the effect of an electric field between two stainless steel feeder electrodes, grapheme layers at the anodic pole of the wireless graphite were oxidized into colloidal dispersion of GO, which migrated electrophoretically towards the anodic side of the cell, and deposited in the form of rGO (d(002) = 0.395 nm) by van der Waals forces. For substrates chemically more susceptible to the high anodic voltage, we show that the electrochemical setup can be adapted by placing the latter between the wireless graphite and the stainless steel feeder anode. This method is straightforward, inexpensive, environmentally-friendly, and could be easily scaled up for high yield and large area production of rGO thin films. PMID- 26883174 TI - Surface Diffusion Directed Growth of Anisotropic Graphene Domains on Different Copper Lattices. AB - Anisotropic graphene domains are of significant interest since the electronic properties of pristine graphene strongly depend on its size, shape, and edge structures. In this work, considering that the growth of graphene domains is governable by the dynamics of the graphene-substrate interface during growth, we investigated the shape and defects of graphene domains grown on copper lattices with different indices by chemical vapor deposition of methane at either low pressure or atmospheric pressure. Computational modeling identified that the crystallographic orientation of copper strongly influences the shape of the graphene at low pressure, yet does not play a critical role at atmospheric pressure. Moreover, the defects that have been previously observed in the center of four-lobed graphene domains grown under low pressure conditions were demonstrated for the first time to be caused by a lattice mismatch between graphene and the copper substrate. PMID- 26883176 TI - Electronic Effects of Aluminum Complexes in the Copolymerization of Propylene Oxide with Tricyclic Anhydrides: Access to Well-Defined, Functionalizable Aliphatic Polyesters. AB - The synthesis of well-defined and functionalizable aliphatic polyesters remains a key challenge in the advancement of emerging drug delivery and self-assembly technologies. Herein, we investigate the factors that influence the rates of undesirable transesterification and epimerization side reactions at high conversion in the copolymerization of tricyclic anhydrides with excess propylene oxide using aluminum salen catalysts. The structure of the tricyclic anhydride, the molar ratio of the aluminum catalyst to the nucleophilic cocatalyst, and the Lewis acidity of the aluminum catalyst all influence the rates of these side reactions. Optimal catalytic activity and selectivity against these side reactions requires a careful balance of all these factors. Effective suppression of undesirable transesterification and epimerization was achieved even with sterically unhindered monomers using a fluorinated aluminum salph complex with a substoichiometric amount of a nucleophilic cocatalyst. This process can be used to synthesize well-defined block copolymers via a sequential addition strategy. PMID- 26883175 TI - Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model. AB - Low correlations of cell culture data with clinical outcomes pose major medical challenges with costly consequences. While the majority of biomaterials are tested using in vitro cell monocultures, the importance of synergistic interactions between different cell types on paracrine signalling has recently been highlighted. In this proof-of-concept study, we asked whether the first contact of surfaces with whole human blood could steer the tissue healing response. This hypothesis was tested using alkali-treatment of rough titanium (Ti) surfaces since they have clinically been shown to improve early implant integration and stability, yet blood-free in vitro cell cultures poorly correlated with in vivo tissue healing. We show that alkali-treatment, compared to native Ti surfaces, increased blood clot thickness, including platelet adhesion. Strikingly, blood clots with entrapped blood cells in synergistic interactions with fibroblasts, but not fibroblasts alone, upregulated the secretion of major factors associated with fast healing. This includes matrix metalloproteinases (MMPs) to break down extracellular matrix and the growth factor VEGF, known for its angiogenic potential. Consequently, in vitro test platforms, which consider whole blood-implant interactions, might be superior in predicting wound healing in response to biomaterial properties. PMID- 26883177 TI - Second-line therapy for advanced pancreatic cancer: evaluation of prognostic factors and review of current literature. AB - BACKGROUND: FOLFIRINOX is a standard first-line treatment for advanced pancreatic cancer (aPC) and no accepted second-line regimen exists. MATERIAL & METHODS: We enrolled 71 aPC patients progressed to modified FOLFIRINOX (mFOLFIRINOX) treated with second-line chemotherapy. RESULTS: Five partial responses (7.1%) and 19 (27.1%) disease stabilizations were reported. After a median follow-up of 20.1 months, median progression-free survival was 2.5 months (95% CI: 2.1-2.9 months) and median overall survival was 6.2 months (95% CI: 5.3-7.1 months). At multivariate analysis, CA19.9 level >= 59 upper normal limit resulted associated with worse survival (hazard ratio: 2.32; 95% CI: 1.12-4.78; p = 0.023). CONCLUSION: Salvage chemotherapy could be useful for a subgroup of aPC patients. Prognostic factors might be helpful to identify patients with greater benefit. PMID- 26883178 TI - In situ Raman spectroscopy of carbon-coated ZnFe2O4 anode material in Li-ion batteries - investigation of SEI growth. AB - The (de)lithiation process of carbon-coated ZnFe2O4 has been investigated by in situ Raman spectroscopy. Solid electrolyte interphase (SEI) products were detected. Their detection may result from a temporary surface enhancement Raman effect from Zn nanoparticles formed in the conversion reaction at a potential that coincides with SEI formation. PMID- 26883179 TI - High-Performance Flexible Solid-State Carbon Cloth Supercapacitors Based on Highly Processible N-Graphene Doped Polyacrylic Acid/Polyaniline Composites. AB - Improving the solubility of conductive polymers to facilitate processing usually decreases their conductivity, and they suffer from poor cycling stability due to swelling-shrinking during charging cycles. We circumvent these problems with a novel preparation method for nitrogen-doped graphene (NG) enhanced polyacrylic acid/polyaniline (NG-PAA/PANI) composites, ensuring excellent processibility for scalable production. The content of PANI is maximized under the constraint of still allowing defect-free coatings on filaments of carbon cloth (CC). The NG content is then adjusted to optimize specific capacitance. The optimal CC electrodes have 32 wt.% PANI and 1.3 wt.% NG, thus achieving a high capacitance of 521 F/g at 0.5 F/g. A symmetric supercapacitor made from 20 wt.% PANI CC electrodes has more than four times the capacitance (68 F/g at 1 A/g) of previously reported flexible capacitors based on PANI-carbon nanotube composites, and it retains the full capacitance under large bending angles. The capacitor exhibits high energy and power densities (5.8 Wh/kg at 1.1 kW/kg), a superior rate capability (still 81% of the 1 A/g capacitance at 10 A/g), and long-term electrochemical stability (83.2% retention after 2000 cycles). PMID- 26883180 TI - Genome-wide DNA methylation analysis in hepatocellular carcinoma. AB - Epigenetic changes as well as genetic changes are mechanisms of tumorigenesis. We aimed to identify novel genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC (the discovery set). The microarray analysis revealed that there were 2,670 CpG sites that significantly differed in regards to the methylation level between the tumor and non-tumor liver tissues; 875 were significantly hypermethylated and 1,795 were significantly hypomethylated in the HCC tumors compared to the non tumor tissues. Further analyses using methylation-specific PCR, combined with expression analysis, in the validation set of primary HCC showed that, in addition to three known tumor-suppressor genes (APC, CDKN2A, and GSTP1), eight genes (AKR1B1, GRASP, MAP9, NXPE3, RSPH9, SPINT2, STEAP4, and ZNF154) were significantly hypermethylated and downregulated in the HCC tumors compared to the non-tumor liver tissues. Our results suggest that epigenetic silencing of these genes may be associated with HCC. PMID- 26883181 TI - Global Health Governance and Global Power: A Critical Commentary on the Lancet University of Oslo Commission Report. AB - The Lancet-University of Oslo Commission Report on Global Governance for Health provides an insightful analysis of the global health inequalities that result from transnational activities consequent on what the authors call contemporary "global social norms." Our critique is that the analysis and suggested reforms to prevailing institutions and practices are confined within the perspective of the dominant-although unsustainable and inequitable-market-oriented, neoliberal development model of global capitalism. Consequently, the report both elides critical discussion of many key forms of material and political power under conditions of neoliberal development and governance that shape the nature and priorities of the global governance for health, and fails to point to the extent of changes required to sustainably improve global health. We propose that an alternative concept of progress-one grounded in history, political economy, and ecologically responsible health ethics-is sorely needed to better address challenges of global health governance in the new millennium. This might be premised on global solidarity and the "development of sustainability." We argue that the prevailing market civilization model that lies at the heart of global capitalism is being, and will further need to be, contested to avoid contradictions and dislocations associated with the commodification and privatization of health. PMID- 26883182 TI - The devil is in the details: the effect of population structure on demographic inference. PMID- 26883183 TI - Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species. AB - Climatic differences across a taxon's range may be associated with specific bioenergetic demands and may result in genetics-based metabolic adaptation, particularly in aquatic ectothermic organisms that rely on heat exchange with the environment to regulate key physiological processes. Extending down the east coast of Australia, the Great Dividing Range (GDR) has a strong influence on climate and the evolutionary history of freshwater fish species. Despite the GDR acting as a strong contemporary barrier to fish movement, many species, and species with shared ancestries, are found on both sides of the GDR, indicative of historical dispersal events. We sequenced complete mitogenomes from the four extant species of the freshwater cod genus Maccullochella, two of which occur on the semi-arid, inland side of the GDR, and two on the mesic coastal side. We constructed a dated phylogeny and explored the relative influences of purifying and positive selection in the evolution of mitogenome divergence among species. Results supported mid- to late-Pleistocene divergence of Maccullochella across the GDR (220-710 thousand years ago), bringing forward previously reported dates. Against a background of pervasive purifying selection, we detected potentially functionally relevant fixed amino acid differences across the GDR. Although many amino acid differences between inland and coastal species may have become fixed under relaxed purifying selection in coastal environments rather than positive selection, there was evidence of episodic positive selection acting on specific codons in the Mary River coastal lineage, which has consistently experienced the warmest and least extreme climate in the genus. PMID- 26883184 TI - Spatial patterns of AFLP diversity in Bulbophyllum occultum (Orchidaceae) indicate long-term refugial isolation in Madagascar and long-distance colonization effects in La Reunion. AB - Bulbophyllum occultum, an epiphytic orchid mainly distributed in the rainforests of (north)eastern Madagascar and La Reunion, represents an interesting model case for testing the effects of anthropogenic vs historical (e.g., climate induced) habitat isolation and long-distance colonization on the genetic structure of plant species with disjunct distributions in the Madagascan region. To this aim, we surveyed amplified fragment length polymorphisms (AFLPs) across 13 populations in Madagascar and nine in La Reunion (206 individuals in total). We found overall high levels of population subdivision (Phi(PT)=0.387) and low within-population diversity (H(E), range: 0.026-0.124), indicating non-equilibrium conditions in a mainly selfing species. There was no impact of recent deforestation (Madagascar) or habitat disturbance (La Reunion) detectable on AFLP diversity. K-means clustering and BARRIER analyses identified multiple gene pools and several genetic breaks, both within and among islands. Inter-island levels of population genetic diversity and subdivision were similar, whereby inter-individual divergence in flower colour explained a significant part of gene pool divergence in La Reunion. Our results suggest that (i) B. occultum persisted across multiple isolated ('refugial') regions along the eastern rainforest corridor of Madagascar over recent climatic cycles and (ii) populations in La Reunion arose from either single or few independent introductions from Madagascar. High selfing rates and sufficient time for genetic drift likely promoted unexpectedly high population genetic and phenotypic (flower colour) differentiation in La Reunion. Overall, this study highlights a strong imprint of history on the genetic structure of a low-gene-dispersing epiphytic orchid from the Madagascan region. PMID- 26883185 TI - 61Ni synchrotron radiation-based Mossbauer spectroscopy of nickel-based nanoparticles with hexagonal structure. AB - We measured the synchrotron-radiation (SR)-based Mossbauer spectra of Ni-based nanoparticles with a hexagonal structure that were synthesised by chemical reduction. To obtain Mossbauer spectra of the nanoparticles without (61)Ni enrichment, we developed a measurement system for (61)Ni SR-based Mossbauer absorption spectroscopy without X-ray windows between the (61)Ni84V16 standard energy alloy and detector. The counting rate of the (61)Ni nuclear resonant scattering in the system was enhanced by the detection of internal conversion electrons and the close proximity between the energy standard and the detector. The spectrum measured at 4 K revealed the internal magnetic field of the nanoparticles was 3.4 +/- 0.9 T, corresponding to a Ni atomic magnetic moment of 0.3 Bohr magneton. This differs from the value of Ni3C and the theoretically predicted value of hexagonal-close-packed (hcp)-Ni and suggested the nanoparticle possessed intermediate carbon content between hcp-Ni and Ni3C of approximately 10 atomic % of Ni. The improved (61)Ni Mossbauer absorption measurement system is also applicable to various Ni materials without (61)Ni enrichment, such as Ni hydride nanoparticles. PMID- 26883186 TI - Quality of life of people living with HIV/AIDS: a cross-country comparison study of Finland and Portugal. AB - The premises underlying the development of the World Health Organization Quality of Life (WHOQOL) instruments provide a convincing rationale for comparing quality of life (QoL) across countries. The aim of the present study was to compare the QoL of patients living with HIV infection in Finland and in Portugal, and to examine the contribution of the QoL domains to the overall QoL in these two countries. The sample comprised 453 patients from Finland (76.3% male; mean age = 46.50) and 975 from Portugal (69.2% male; mean age = 40.98), all living with HIV. QoL data were collected by use of the WHOQOL-HIV-Bref questionnaire. Significant country differences were found in QoL domains and specific facets. Patients from Finland reported markedly higher scores on all six QoL domains and general facet, than did their Portuguese counterparts. Regarding the specific facets of the WHOQOL-HIV-Bref, patients from Finland also reported significantly higher scores on 24 out of 29. The exceptions were dependence on medications and treatment, positive feelings, personal relationships, sexual activity, and on spirituality, religion and personal beliefs. Regression analyses showed that physical, psychological, and independence domains contributed to overall QoL among the Finnish patients (R(2) = 0.63), whereas among the Portuguese, the domains significantly associated with overall QoL were physical, psychological, independence, and environment (R(2) = 0.48). Country differences in QoL domains and specific facets may reflect sociocultural differences between southern and northern Europe. PMID- 26883187 TI - Does size matter? Examining the effect of obesity on inpatient amputation rehabilitation outcomes. AB - Purpose This study investigated whether obesity impacted clinical outcomes of patients at discharge from inpatient amputation rehabilitation. Method This was a retrospective chart review examining admissions for lower extremity amputation rehabilitation at a Canadian Regional Amputee Rehabilitation Programme between December 2011 and June 2014. Discharge outcomes were predefined as the two-minute walk test (2MWT), the L-test of functional mobility and the SIGAM score. These were compared between each body mass index (BMI) group (underweight < 18.4 kg/m2, normal between 18.5 and 24.9 kg/m2, overweight between 25.0 and 29.9 kg/m2 and obese greater or equal to 30 kg/m2) as a whole and within transtibial, transfemoral and bilateral amputation groups. Results Of the 289 admissions meeting inclusion criteria, only underweight patients walked significantly less distance on the 2MWT than normal weight patients. There were group differences in the L-test, but post hoc testing was unable to qualify the differences. No significant difference was found in the SIGAM score. There were no significant differences found in the 2MWT, L-test or SIGAM when patients were grouped by amputation level. Conclusions Obesity does not appear to significantly impact inpatient amputation rehabilitation outcomes such as the 2MWT, L-test or SIGAM score. As such, obesity should not be a deciding factor as to whether a patient is offered rehabilitation. Implications for Rehabilitation Obesity is increasing in prevalence and is comorbid with peripheral vascular disease and diabetes, the leading causes of lower extremity amputation. Function is compromised in the obese general population when compared to non-obese individuals. Obesity does not seem to confer a disadvantage with regards to validated outcomes, such as the 2 min walk test, L-test or SIGAM score at discharge after inpatient amputation rehabilitation. Obesity should not be a barrier to offering inpatient rehabilitation to amputation patients. PMID- 26883188 TI - Benefits of training India's quacks. PMID- 26883189 TI - The efficacy of blueberry and grape seed extract combination on triple therapy for Helicobacter pylori eradication: a randomised controlled trial. AB - Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per protocol analysis (94.64% versus 84.62%, p = 0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy. PMID- 26883190 TI - Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma. AB - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in acute and chronic inflammatory diseases. MIF is overexpressed in various tumors. It displays a number of functions that provide a direct link between the process of inflammation and tumor growth. Our group recently identified the MIF-receptor CD74 as an independent prognostic factor for overall survival in patients with malignant pleural mesothelioma.In the present study, we compared the levels of expression of MIF and CD74 in different human mesothelioma cell lines and investigated their physiopathological functions in vitro and in vivo.Human mesothelioma cells expressed more CD74 and secreted less MIF than non tumoral MeT5A cells, suggesting a higher sensitivity to MIF. In mesothelioma cells, high MIF levels were associated with a high multiplication rate of cells. In vitro, reduction of MIF or CD74 levels in both mesothelioma cell lines showed that the MIF/CD74 signaling pathway promoted tumor cell proliferation and protected MPM cells from apoptosis. Finally, mesothelioma cell lines expressing high CD74 levels had a low tumorigenic potential after xenogeneic implantation in athymic nude mice.All these data highlight the complexity of the MIF/CD74 signaling pathway in the development of mesothelioma. PMID- 26883191 TI - CCL-34, a synthetic toll-like receptor 4 activator, modulates differentiation and maturation of myeloid dendritic cells. AB - CCL-34, a synthetic alpha-galactosylceramide analog, has been reported as an activator of toll-like receptor 4 (TLR4) in macrophages. TLR4 is highly expressed in dendritic cell (DC) and several TLR4 agonists are known to trigger DC maturation. We herein evaluated the effect of CCL-34 on DC maturation. Human CD14+ monocyte-derived immature DC were treated with CCL-34, its inactive structural analog CCL-44, or LPS to assess the DC maturation. CCL-34 induced DC maturation according to their characteristically dendrite-forming morphology, CD83 expression and IL-12p70 production. The allostimulatory activity of DC on proliferation of naive CD4+CD45+RA+ T cells and their secretion of interferon gamma was increased by CCL-34. Phagocytosis, an important function of immature DC, was reduced after CCL-34 treatment. All these effects related to DC maturation were evidently induced by positive control LPS but not by CCL-44 treatment. TLR4 neutralization impaired human DC maturation triggered by CCL-34. The induction of IL-12, a hallmark of DC maturation, by CCL-34 and LPS was only evident in TLR4-competent C3H/HeN, but not in TLR4-defective C3H/HeJ mice. CCL-34 could further elicit the antigen presentation capability in mice inoculated with doxorubicin-treated colorectal cancer cells. In summary, CCL-34 triggers DC maturation via a TLR4-dependent manner, which supports its potential application as an immunostimulator. PMID- 26883192 TI - Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma. AB - The more accurate biomarkers have long been desired for hepatocellular carcinoma (HCC). Here, we characterized global large-scale proteomics of multistep hepatocarcinogenesis in an attempt to identify novel biomarkers for HCC. Quantitative data of 37874 sequences and 3017 proteins during hepatocarcinogenesis were obtained in cohort 1 of 75 samples (5 pooled groups: normal livers, hepatitis livers, cirrhotic livers, peritumoral livers, and HCC tissues) by iTRAQ 2D LC-MS/MS. The diagnostic performance of the top six most upregulated proteins in HCC group and HSP70 as reference were subsequently validated in cohort 2 of 114 samples (hepatocarcinogenesis from normal livers to HCC) using immunohistochemistry. Of seven candidate protein markers, PARP1, GS and NDRG1 showed the optimal diagnostic performance for HCC. PARP1, as a novel marker, showed comparable diagnostic performance to that of classic markers GS and NDRG1 in HCC (AUCs = 0.872, 0.856 and 0.792, respectively). A significant higher AUC of 0.945 was achieved when three markers combined. For diagnosis of HCC, the sensitivity and specificity were 88.2% and 81.0% when at least two of the markers were positive. Similar diagnostic values of PARP1, GS and NDRG1 were confirmed by immunohistochemistry in cohort 3 of 180 HCC patients. Further analysis indicated that PARP1 and NDRG1 were associated with some clinicopathological features, and the independent prognostic factors for HCC patients. Overall, global large-scale proteomics on spectrum of multistep hepatocarcinogenesis are obtained. PARP1 is a novel promising diagnostic/prognostic marker for HCC, and the three-marker panel (PARP1, GS and NDRG1) with excellent diagnostic performance for HCC was established. PMID- 26883193 TI - Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy. AB - Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies in the treatment of HER2-positive breast cancer is a major clinical problem. To identify pathways linked to resistance, we generated HER2-positive breast cancer cell lines which are resistant to either lapatinib or AZD8931, two pan-HER family kinase inhibitors. Resistance was HER2 independent and was associated with epithelial-to-mesenchymal transition (EMT), resulting in increased proliferation and migration of the resistant cells. Using a global proteomics approach, we identified a novel set of EMT-associated proteins linked to HER2-independent resistance. We demonstrate that a subset of these EMT-associated genes is predictive of prognosis within the ERBB2 subtype of human breast cancers. Furthermore, targeting the EMT-associated kinases Src and Axl potently inhibited proliferation of the resistant cells, and inhibitors to these kinases may provide additional options for the treatment of HER2-independent resistance in tumors. PMID- 26883194 TI - Integrated genomic approaches identify upregulation of SCRN1 as a novel mechanism associated with acquired resistance to erlotinib in PC9 cells harboring oncogenic EGFR mutation. AB - Therapies targeting the tyrosine kinase activity of Epidermal Growth Factor Receptor (EGFR) have been proven to be effective in treating a subset of non small cell lung cancer (NSCLC) patients harboring activating EGFR mutations. Inevitably these patients develop resistance to the EGFR-targeted tyrosine kinase inhibitors (TKIs). Here, we performed integrated genomic analyses using an in vitro system to uncover alternative genomic mechanisms responsible for acquired resistance to EGFR-TKIs. Specifically, we identified 80 genes whose expression is significantly increased in the erlotinib-resistant clones. RNAi-based systematic synthetic lethal screening of these candidate genes revealed that suppression of one upregulated transcript, SCRN1, a secernin family member, restores sensitivity to erlotinib by enhancing inhibition of PI3K/AKT signaling pathway. Furthermore, immunohistochemical analysis revealed increased levels of SCRN1 in 5 of 11 lung tumor specimens from EGFR-TKIs resistant patients. Taken together, we propose that upregulation of SCRN1 is an additional mechanism associated with acquired resistance to EGFR-TKIs and that its suppression serves as a novel therapeutic strategy to overcome drug resistance in these patients. PMID- 26883195 TI - Osteoactivin (GPNMB) ectodomain protein promotes growth and invasive behavior of human lung cancer cells. AB - The potential application of GPNMB/OA as a therapeutic target for lung cancer will require a greater understanding of the impact of GPNMB/OA ectodomain (ECD) protein shedding into tumor tissues. Thus, in this work we characterized GPNMB/OA expression and extent of shedding of its ECD protein while evaluating the impact on lung cancer progression using three non-small cell lung cancer (NSCLC) cell lines: A549, SK-MES-1 and calu-6. We observed a direct correlation (R2 = 0.89) between GPNMB/OA expression on NSCLC cells and the extent of GPNMB/OA ECD protein shedding. Meanwhile, siRNA-mediated knockdown of GPNMB/OA in cancer cells significantly reduced GPNMB/OA ECD protein shedding, migration, invasion and adhesion to extracellular matrix materials. Also, exogenous treatment of cancer cells (expressing low GPNMB/OA) with recombinant GPNMB/OA protein (rOA) significantly facilitated cell invasion and migration, but the effects of rOA was negated by inclusion of a selective RGD peptide. Further studies in athymic (nu/nu) mice-bearing calu-6 showed that intratumoral supplementation with rOA effectively facilitated in vivo tumor growth as characterized by a high number of proliferating cells (Ki67 staining) coupled with a low number of apoptotic cells. Taken together, our results accentuate the relevance of GPNMB/OA ECD protein shedding to progression of lung cancer. Thus, strategies that suppress GPNMB/OA expression on lung cancer cells as well as negate shedding of GPNMB/OA ECD protein are worthy of consideration in lung cancer therapeutics. PMID- 26883196 TI - Wip1 phosphatase: between p53 and MAPK kinases pathways. AB - Cells undergoing oncogenic transformation frequently inactivate tumor suppressor pathways that could prevent their uncontrolled growth. Among those pathways p53 and p38MAPK pathways play a critical role in regulation of cell cycle, senescence and cell death in response to activation of oncogenes, stress and DNA damage. Consequently, these two pathways are important in determining the sensitivity of tumor cells to anti-cancer treatment. Wild type p53-induced phosphatase, Wip1, is involved in governance of both pathways. Recently, strategies directed to manipulation with Wip1 activity proposed to advance current day anticancer treatment and novel chemical compounds synthesized to improve specificity of manipulation with Wip1 activity. Here we reviewed the history of Wip1 studies in vitro and in vivo, in genetically modified animal models that support Wip1 role in tumorigenesis through regulation of p53 and p38MAPK pathways. Based on our knowledge we propose several recommendations for future more accurate studies of Wip1 interactions with other pathways involved in tumorigenesis using recently developed tools and for adoption of Wip1 manipulation strategies in anti-cancer therapy. PMID- 26883197 TI - Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy. AB - Cancer testis antigens (CTAs) are promising cancer associated antigens in solid tumors, but in acute myeloid leukemia, dense promoter methylation silences their expression. Leukemia cell lines exposed to HMAs induce expression of CTAs. We hypothesized that AML patients treated with standard of care decitabine (20mg/m2 per day for 10 days) would demonstrate induced expression of CTAs. Peripheral blood blasts serially isolated from AML patients treated with decitabine were evaluated for CTA gene expression and demethylation. Induction of NY-ESO-1 and MAGEA3/A6, were observed following decitabine. Re-expression of NY-ESO-1 and MAGEA3/A6 was associated with both promoter specific and global (LINE-1) hypomethylation. NY-ESO-1 and MAGEA3/A6 mRNA levels were increased irrespective of clinical response, suggesting that these antigens might be applicable even in patients who are not responsive to HMA therapy. Circulating blasts harvested after decitabine demonstrate induced NY-ESO-1 expression sufficient to activate NY-ESO-1 specific CD8+ T-cells. Induction of CTA expression sufficient for recognition by T-cells occurs in AML patients receiving decitabine. Vaccination against NY-ESO-1 in this patient population is feasible. PMID- 26883198 TI - CRP2, a new invadopodia actin bundling factor critically promotes breast cancer cell invasion and metastasis. AB - A critical process underlying cancer metastasis is the acquisition by tumor cells of an invasive phenotype. At the subcellular level, invasion is facilitated by actin-rich protrusions termed invadopodia, which direct extracellular matrix (ECM) degradation. Here, we report the identification of a new cytoskeletal component of breast cancer cell invadopodia, namely cysteine-rich protein 2 (CRP2). We found that CRP2 was not or only weakly expressed in epithelial breast cancer cells whereas it was up-regulated in mesenchymal/invasive breast cancer cells. In addition, high expression of the CRP2 encoding gene CSRP2 was associated with significantly increased risk of metastasis in basal-like breast cancer patients. CRP2 knockdown significantly reduced the invasive potential of aggressive breast cancer cells, whereas it did not impair 2D cell migration. In keeping with this, CRP2-depleted breast cancer cells exhibited a reduced capacity to promote ECM degradation, and to secrete and express MMP-9, a matrix metalloproteinase repeatedly associated with cancer progression and metastasis. In turn, ectopic expression of CRP2 in weakly invasive cells was sufficient to stimulate cell invasion. Both GFP-fused and endogenous CRP2 localized to the extended actin core of invadopodia, a structure primarily made of actin bundles. Purified recombinant CRP2 autonomously crosslinked actin filaments into thick bundles, suggesting that CRP2 contributes to the formation/maintenance of the actin core. Finally, CRP2 depletion significantly reduced the incidence of lung metastatic lesions in two xenograft mouse models of breast cancer. Collectively, our data identify CRP2 as a new cytoskeletal component of invadopodia that critically promotes breast cancer cell invasion and metastasis. PMID- 26883199 TI - Improved cell metabolism prolongs photoreceptor survival upon retinal-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy. AB - Age-related macular degeneration (AMD) is characterized by malfunction and loss of retinal-pigmented epithelium (RPE) cells. Because the RPE transfers nutrients from the choriocapillaris to photoreceptor (PR), PRs are affected as well. Geographic atrophy (GA) is an advanced form of AMD characterized by severe vision impairment due to RPE loss over large areas. Currently there is no treatment to delay the degeneration of nutrient deprived PRs once RPE cells die. Here we show that cell-autonomous activation of the key regulator of cell metabolism, the kinase mammalian target of rapamycin complex 1 (mTORC1), delays PR death in the sodium iodate induced model of RPE atrophy. Consistent with this finding loss of mTORC1 in cones accelerates cone death as cones fail to balance demand with supply. Interestingly, promoting rod survival does not promote cone survival in this model of RPE atrophy as both, rods and cones suffer from a sick and dying RPE. The findings suggest that activation of metabolic genes downstream of mTORC1 can serve as a strategy to prolong PR survival when RPE cells malfunction or die. PMID- 26883200 TI - SREBP-2 promotes stem cell-like properties and metastasis by transcriptional activation of c-Myc in prostate cancer. AB - Sterol regulatory element-binding protein-2 (SREBP-2) transcription factor mainly controls cholesterol biosynthesis and homeostasis in normal cells. The role of SREBP-2 in lethal prostate cancer (PCa) progression remains to be elucidated. Here, we showed that expression of SREBP-2 was elevated in advanced pathologic grade and metastatic PCa and significantly associated with poor clinical outcomes. Biofunctional analyses demonstrated that SREBP-2 induced PCa cell proliferation, invasion and migration. Furthermore, overexpression of SREBP-2 increased the PCa stem cell population, prostasphere-forming ability and tumor initiating capability, whereas genetic silencing of SREBP-2 inhibited PCa cell growth, stemness, and xenograft tumor growth and metastasis. Clinical and mechanistic data showed that SREBP-2 was positively correlated with c-Myc and induced c-Myc activation by directly interacting with an SREBP-2-binding element in the 5'-flanking c-Myc promoter region to drive stemness and metastasis. Collectively, these clinical and experimental results reveal a novel role of SREBP-2 in the induction of a stem cell-like phenotype and PCa metastasis, which sheds light on translational potential by targeting SREBP-2 as a promising therapeutic approach in PCa. PMID- 26883201 TI - Decision aid on breast cancer screening reduces attendance rate: results of a large-scale, randomized, controlled study by the DECIDEO group. AB - Controversies regarding the benefits of breast cancer screening programs have led to the promotion of new strategies taking into account individual preferences, such as decision aid. The aim of this study was to assess the impact of a decision aid leaflet on the participation of women invited to participate in a national breast cancer screening program. This Randomized, multicentre, controlled trial. Women aged 50 to 74 years, were randomly assigned to receive either a decision aid or the usual invitation letter. Primary outcome was the participation rate 12 months after the invitation. 16 000 women were randomized and 15 844 included in the modified intention-to-treat analysis. The participation rate in the intervention group was 40.25% (3174/7885 women) compared with 42.13% (3353/7959) in the control group (p = 0.02). Previous attendance for screening (RR = 6.24; [95%IC: 5.75-6.77]; p < 0.0001) and medium household income (RR = 1.05; [95%IC: 1.01-1.09]; p = 0.0074) were independently associated with attendance for screening. This large-scale study demonstrates that the decision aid reduced the participation rate. The decision aid activate the decision making process of women toward non-attendance to screening. These results show the importance of promoting informed patient choices, especially when those choices cannot be anticipated. PMID- 26883202 TI - A novel small molecule STAT3 inhibitor, LY5, inhibits cell viability, colony formation, and migration of colon and liver cancer cells. AB - Signal Transducer and Activator of Transcription 3 (STAT3) is persistently activated in human liver and colon cancer cells and is required for cancer cell viability, survival and migration. Therefore, inhibition of STAT3 signaling may be a viable therapeutic approach for these two cancers. We recently designed a non-peptide small molecule STAT3 inhibitor, LY5, using in silico site-directed Fragment-based drug design (FBDD). The inhibitory effect on STAT3 phosphorylation, cell viability, migration and colony forming ability by LY5 were examined in human liver and colon cancer cells. We demonstrated that LY5 inhibited constitutive Interleukin-6 (IL-6)-induced STAT3 phosphorylation, STAT3 nuclear translocation, decreased STAT3 downstream targeted gene expression and induced apoptosis in liver and colon cancer cells. LY5 had little effect on STAT1 phosphorylation mediated by IFN-gamma. Inhibition of persistent STAT3 phosphorylation by LY5 also inhibited colony formation, cell migration, and decreased the viability of liver cancer and colon cancer cells. Furthermore, LY5 inhibited STAT3 phosphorylation and suppressed colon tumor growth in a mouse model in vivo. Our results suggest that LY5 is a potent STAT3 inhibitor and may be a potential drug candidate for liver and colon cancer therapy. PMID- 26883203 TI - Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer. AB - Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC).We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression.Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID- 26883204 TI - Altools: a user friendly NGS data analyser. AB - BACKGROUND: Genotyping by re-sequencing has become a standard approach to estimate single nucleotide polymorphism (SNP) diversity, haplotype structure and the biodiversity and has been defined as an efficient approach to address geographical population genomics of several model species. To access core SNPs and insertion/deletion polymorphisms (indels), and to infer the phyletic patterns of speciation, most such approaches map short reads to the reference genome. Variant calling is important to establish patterns of genome-wide association studies (GWAS) for quantitative trait loci (QTLs), and to determine the population and haplotype structure based on SNPs, thus allowing content-dependent trait and evolutionary analysis. Several tools have been developed to investigate such polymorphisms as well as more complex genomic rearrangements such as copy number variations, presence/absence variations and large deletions. The programs available for this purpose have different strengths (e.g. accuracy, sensitivity and specificity) and weaknesses (e.g. low computation speed, complex installation procedure and absence of a user-friendly interface). Here we introduce Altools, a software package that is easy to install and use, which allows the precise detection of polymorphisms and structural variations. RESULTS: Altools uses the BWA/SAMtools/VarScan pipeline to call SNPs and indels, and the dnaCopy algorithm to achieve genome segmentation according to local coverage differences in order to identify copy number variations. It also uses insert size information from the alignment of paired-end reads and detects potential large deletions. A double mapping approach (BWA/BLASTn) identifies precise breakpoints while ensuring rapid elaboration. Finally, Altools implements several processes that yield deeper insight into the genes affected by the detected polymorphisms. Altools was used to analyse both simulated and real next-generation sequencing (NGS) data and performed satisfactorily in terms of positive predictive values, sensitivity, the identification of large deletion breakpoints and copy number detection. CONCLUSIONS: Altools is fast, reliable and easy to use for the mining of NGS data. The software package also attempts to link identified polymorphisms and structural variants to their biological functions thus providing more valuable information than similar tools. PMID- 26883206 TI - Multi-platform mass spectrometry analysis of the CSF and plasma metabolomes of rigorously matched amyotrophic lateral sclerosis, Parkinson's disease and control subjects. AB - Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are protein aggregation diseases that lack clear molecular etiologies. Biomarkers could aid in diagnosis, prognosis, planning of care, drug target identification and stratification of patients into clinical trials. We sought to characterize shared and unique metabolite perturbations between ALS and PD and matched controls selected from patients with other diagnoses, including differential diagnoses to ALS or PD that visited our clinic for a lumbar puncture. Cerebrospinal fluid (CSF) and plasma from rigorously age-, sex- and sampling-date matched patients were analyzed on multiple platforms using gas chromatography (GC) and liquid chromatography (LC)-mass spectrometry (MS). We applied constrained randomization of run orders and orthogonal partial least squares projection to latent structure effect projections (OPLS-EP) to capitalize upon the study design. The combined platforms identified 144 CSF and 196 plasma metabolites with diverse molecular properties. Creatine was found to be increased and creatinine decreased in CSF of ALS patients compared to matched controls. Glucose was increased in CSF of ALS patients and alpha-hydroxybutyrate was increased in CSF and plasma of ALS patients compared to matched controls. Leucine, isoleucine and ketoleucine were increased in CSF of both ALS and PD. Together, these studies, in conjunction with earlier studies, suggest alterations in energy utilization pathways and have identified and further validated perturbed metabolites to be used in panels of biomarkers for the diagnosis of ALS and PD. PMID- 26883207 TI - Pregnancy-induced adaptations of the central circadian clock and maternal glucocorticoids. AB - Maternal physiological adaptations, such as changes to the hypothalamic-pituitary adrenal (HPA) axis, are central to pregnancy success. Circadian variation of the HPA axis is dependent on clock gene rhythms in the hypothalamus, but it is not known whether pregnancy-induced changes in maternal glucocorticoid levels are mediated via this central clock. We hypothesized that hypothalamic expression of clock genes changes across mouse pregnancy and this is linked to altered HPA activity. The anterior hypothalamus and maternal plasma were collected from C57Bl/6J mice prior to pregnancy and on days 6, 10, 14 and 18 of gestation (term=d19), across a 24-h period (0800, 1200, 1600, 2000, 0000, 0400 h). Hypothalamic expression of clock genes and Crh was determined by qPCR, plasma ACTH concentration measured by Milliplex assay and plasma corticosterone concentration by LC-MS/MS. Expression of all clock genes varied markedly across gestation, most notably at mid-gestation when levels of each gene were elevated. The pregnancy-induced increase in maternal corticosterone levels (by up to 14 fold on day 14) was not accompanied by a parallel shift in plasma ACTH (28% lower on day 14 compared with non-pregnant levels). Moreover, while circadian rhythmicity in corticosterone was maintained up to day 14 of gestation, this was effectively lost by day 18. Overall, our data show that the central circadian clock undergoes marked adaptations throughout mouse pregnancy, changes that are likely to contribute to maternal physiological adaptations. Importantly, however, neither hypothalamic clock genes nor plasma ACTH levels appear to drive the marked increase in maternal corticosterone after mid-gestation. PMID- 26883209 TI - Phthalocyanine-cRGD conjugate: synthesis, photophysical properties and in vitro biological activity for targeting photodynamic therapy. AB - An unsymmetrical phthalocyanine conjugated with an RGDyK moiety (6) was synthesized and characterized. Its photophysical properties, including electronic absorption, fluorescence emission (PhiF = 0.20), singlet oxygen quantum yield (PhiDelta = 0.63) and two-photon absorption cross section (TPACS) at different wavelengths were studied. The in vitro cell study data demonstrate that this Pc conjugate possesses significantly high cellular uptake toward the alphanubeta3 positive DU145 prostate cancer cells along with an efficient photocytotoxicity (IC50 = 0.04 MUM), showing this compound is one of the most promising photosensitizers for targeting photodynamic therapy (PDT) of cancer. PMID- 26883208 TI - Psychometric properties of the Japanese version of the Recovery Attitudes Questionnaire (RAQ) among mental health providers: a questionnaire survey. AB - BACKGROUND: "Recovery" is a central concept in mental health, particularly for mental health services and policy-makers. The present study examined the factorial and concurrent validity, internal consistency reliability, and test retest reliability of the Japanese version of the 7-item Recovery Attitudes Questionnaire (RAQ) among mental health service providers in community and inpatient settings in Japan. METHODS: We conducted a cross-sectional questionnaire with a number of eligible professional groups, including psychiatrists, registered/assistant nurses, public health nurses, clinical psychologists, pharmacists, occupational therapists, and social workers. Participants were drawn from two psychiatric hospitals and 56 psychiatric clinics or community service agencies. In total, 331 participants completed the questionnaire. After excluding those with missing RAQ values, 307 participants were included in the analysis; the participants' mean age was 40.2 years and 29.6 % were men. The questionnaire comprised the Japanese version of the 7-item RAQ developed by the present authors, the revised scale of the positive attitudes of staff toward persons with mental disorder (the positive attitudes scale), and the Japanese-language version of the Social Distance Scale (SDSJ). Confirmatory factor analyses were used to examine factorial validity of a two-factor structure reported in a previous study (Borkin et al., 2000) as well as a single-factor structure. Concurrent validity was determined by calculating correlations between RAQ and the other two scales. Internal consistency reliability was assessed with Cronbach's alpha coefficients and inter-item correlations. Test-retest reliability was assessed by the intraclass correlation coefficient (ICC), with a weighted kappa in a subsample of participants (n = 13). RESULTS: The two-factor structure showed acceptable factorial validity. RAQ scores were significantly and positively correlated with the positive attitudes scale, and there was a significant inverse correlation with the SDSJ (p < 0.01). The RAQ had an overall Cronbach's alpha coefficient of 0.64. Four inter-item correlations were not significant. The ICC and weighted kappa values indicated unsatisfactory test retest reliability. CONCLUSION: The Japanese RAQ showed acceptable factorial validity, reasonable concurrent validity, and unsatisfactory reliability in community and inpatient mental health settings in Japan. Further large-scale research is required to ensure robust verification. PMID- 26883210 TI - Knowledge, beliefs and attitudes of physicians in low and middle-income countries regarding interacting with pharmaceutical companies: a systematic review. AB - BACKGROUND: Understanding the perceptions and attitudes of physicians is important. This knowledge assists in the efforts to reduce the impact of their interactions with the pharmaceutical industry on clinical practice. It appears that most studies on such perceptions and attitudes have been conducted in high income countries. The objective was to systematically review the knowledge, beliefs and attitudes of physicians in low and middle-income countries regarding interactions with pharmaceutical companies. METHODS: Eligible studies addressed any type of interaction between physicians and pharmaceutical companies. The outcomes of interest included knowledge, beliefs and attitudes of practicing physicians. The search strategy covered MEDLINE and EMBASE databases. Two reviewers completed in duplicate and independently study selection, data abstraction, and assessment of methodological features. The data synthesis consisted of a narrative summary of the findings stratified by knowledge, beliefs and attitudes. RESULTS: We included ten reports from nine eligible studies, each of which had a number of methodological limitations. Four studies found that the top perceived benefits of this interaction were receiving information and rewards. In five out of eight studies assessing the perception regarding the impact of the interaction on the behavior of physician prescription, the majority of participants believed it to be minor. In one of these studies, participants perceived that impact to be lesser when asked about their own behavior. The attitudes of physicians towards information and rewards provided by pharmaceutical company representatives (PCRs) (assessed in 5 and 2 studies respectively) varied across studies. In the only study assessing their attitudes towards pharmaceutical-sponsored Continuing Medical Education, physicians considered local conferences to have higher impact. Their attitudes towards developing policies restricting physicians' interactions with PCRs were positive in two studies. In one study, the majority of participants did not mind the public knowing that physicians were receiving gifts and awards from drug companies. CONCLUSIONS: This review identified few studies conducted in low and middle-income countries. While physicians generally perceived the impact of interactions on their behavior to be minor, their attitudes toward receiving information and rewards varied across studies. PMID- 26883211 TI - Medical savings accounts: assessing their impact on efficiency, equity and financial protection in health care. AB - Medical savings accounts (MSAs) allow enrolees to withdraw money from earmarked funds to pay for health care. The accounts are usually accompanied by out-of pocket payments and a high-deductible insurance plan. This article reviews the association of MSAs with efficiency, equity, and financial protection. We draw on evidence from four countries where MSAs play a significant role in the financing of health care: China, Singapore, South Africa, and the United States of America. The available evidence suggests that MSA schemes have generally been inefficient and inequitable and have not provided adequate financial protection. The impact of these schemes on long-term health-care costs is unclear. Policymakers and others proposing the expansion of MSAs should make explicit what they seek to achieve given the shortcomings of the accounts. PMID- 26883212 TI - Agromyces insulae sp. nov., an actinobacterium isolated from a soil sample. AB - A novel Gram-reaction-positive, non-motile, aerobic bacterium, designated CFH S0483T, was isolated from a soil sample collected from Catba island in Halong Bay, Vietnam. 16S rRNA gene sequence analysis showed that the strain is a member of the genus Agromyces and has highest 16S rRNA gene sequence similarities with Agromyces humatus DSM 16389T (97.3 %) and Agromyces ramosus DSM 43045T (97.1 %), and similarities < 97.0 % with type strains of other species of the genus Agromyces. Strain CFH S0483T was able to grow at 10-37 degrees C, at pH 7.0-9.0 and tolerated NaCl up to 2.0 % (w/v). The whole-cell sugars were mannose, galactose, glucose and ribose. The isolate contained l-2,4-diaminobutyric acid, d alanine, d-glutamic acid and glycine in the cell-wall peptidoglycan. Strain CFH S0483T exhibited a menaquinone system with MK-12, and the major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The genomic DNA G+C content of strain CFH S0483T was 71.6 mol%. Based on the phylogenetic and phenotypic analysis, and low DNA-DNA hybridization values, strain CFH S0483T could not be classified into any recognized species of the genus Agromyces. Strain CFH S0483T is therefore considered to represent a novel species of the genus Agromyces, for which the name Agromyces insulae sp. nov. is proposed. The type strain is CFH S0483T ( = KCTC 39117T = CCTCC AB 2014301T). PMID- 26883213 TI - Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy. AB - BACKGROUND: There is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy. METHODS: This 3-year, prospective, observational, multicentre study included 1021 participants. Of these, 734 had mild AD (Mini-Mental State Examination (MMSE) score, 20-26) and 287 had moderate AD (MMSE score, 10-19) at the start of ChEI treatment. At baseline and every 6 months, patients were assessed using cognitive, global, instrumental and basic activities of daily living (ADL) scales. Potential predictors of deterioration in moderate AD were analysed using mixed-effects models. RESULTS: The change from baseline between participants with mild and moderate stages of AD after 3 years of ChEI therapy differed significantly on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and basic ADL, but not using the MMSE and instrumental ADL scales. Protective independent factors for better cognitive long-term outcome in the group with moderate AD were older age, higher instrumental ADL ability, no antipsychotics, usage of non-steroidal anti-inflammatory drugs/acetylsalicylic acid, living with family member, lower education and a higher mean dose of ChEI. Apolipoprotein E genotype did not influence the rates of disease progression or the longitudinal outcomes. Prediction models were provided for moderate AD. CONCLUSIONS: More sensitive cognitive measures, such as the ADAS-cog scale, are required to detect a possibly faster deterioration among the participants with moderate AD. This study highlighted the clinical importance of instrumental ADL evaluations in patients at a mild stage of AD, and the importance of optimizing the ChEI dose even for individuals with moderate AD. Solitary living was a risk factor for faster cognitive decline, and probably expanded the need for formal care in the group with moderate AD. The patients with more advanced AD and presumably more pronounced neuroinflammation might have additional cognitive benefits from longer-term treatment with anti-inflammatory drugs. PMID- 26883215 TI - Applicable or non-applicable: investigations of clinical heterogeneity in systematic reviews. AB - BACKGROUND: Clinical heterogeneity can be defined as differences in participant characteristics, types or timing of outcome measurements and intervention characteristics. Clinical heterogeneity in systematic reviews has the possibility to significantly affect statistical heterogeneity leading to inaccurate conclusions and misled decision making. The aim of this study is to identify to what extent investigators are assessing clinical heterogeneity in both Cochrane and non-Cochrane systematic reviews. METHODS: The most recent 100 systematic reviews from the top five journals in medicine-JAMA, Archives of Internal Medicine, British Medical Journal, The Lancet, and PLOS Medicine-and the 100 most recently published and/or updated systematic reviews from Cochrane were collected. Various defined items of clinical heterogeneity were extracted from the included reviews. Investigators used chi-squared tests, logarithmic modeling and linear regressions to determine if the presence of such items served as a predictor for clinical heterogeneity when comparing Cochrane to non-Cochrane reviews. Extracted variables include number of studies, number of participants, presence of quantitative synthesis, exploration of clinical heterogeneity, heterogeneous characteristics explored, basis and methods used for investigating clinical heterogeneity, plotting/visual aids, author contact, inferences from clinical heterogeneity investigation, reporting assessment, and the presence of a priori or post-hoc analysis. RESULTS: A total of 317 systematic reviews were considered, of which 199 were in the final analysis. A total of 81% of Cochrane reviews and 90% of non-Cochrane reviews explored characteristics that are considered aspects of clinical heterogeneity and also described the methods they planned to use to investigate the influence of those characteristics. Only 1% of non-Cochrane reviews and 8% of Cochrane reviews explored the clinical characteristics they initially chose as potential for clinical heterogeneity. Very few studies mentioned clinician training, compliance, brand, co interventions, dose route, ethnicity, prognostic markers and psychosocial variables as covariates to investigate as potentially clinically heterogeneous. Addressing aspects of clinical heterogeneity was not different between Cochrane and non-Cochrane reviews. CONCLUSIONS: The ability to quantify and compare the clinical differences of trials within a meta-analysis is crucial to determining its applicability and use in clinical practice. Despite Cochrane Collaboration emphasis on methodology, the proportion of reviews that assess clinical heterogeneity is less than those of non-Cochrane reviews. Our assessment reveals that there is room for improvement in assessing clinical heterogeneity in both Cochrane and non-Cochrane reviews. PMID- 26883214 TI - Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane. AB - BACKGROUND: Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE. Two main aims of this work were: (1) to assess whether chronic hyperammonemia increases inflammatory factors in the hippocampus and if this is associated with microglia and/or astrocytes activation and (2) to assess whether hyperammonemia-induced neuroinflammation in the hippocampus is associated with altered membrane expression of glutamate and GABA receptors and spatial learning impairment. There are no specific treatments for cognitive alterations in patients with MHE. A third aim was to assess whether treatment with sulforaphane enhances endogenous the anti-inflammatory system, reduces neuroinflammation in the hippocampus of hyperammonemic rats, and restores spatial learning and if normalization of receptor membrane expression is associated with learning improvement. METHODS: We analyzed the following in control and hyperammonemic rats, treated or not with sulforaphane: (1) microglia and astrocytes activation by immunohistochemistry, (2) markers of pro inflammatory (M1) (IL-1beta, IL-6) and anti-inflammatory (M2) microglia (Arg1, YM 1) by Western blot, (3) membrane expression of GABA, AMPA, and NMDA receptors using the BS3 cross-linker, and (4) spatial learning using the radial maze. RESULTS: The results reported show that hyperammonemia induces astrocytes and microglia activation in the hippocampus, increasing pro-inflammatory cytokines IL 1beta and IL-6. This is associated with altered membrane expression of AMPA, NMDA, and GABA receptors which would be responsible for altered neurotransmission and impairment of spatial learning in the radial maze. Treatment with sulforaphane promotes microglia differentiation from pro-inflammatory M1 to anti inflammatory M2 phenotype and reduces activation of astrocytes in hyperammonemic rats. This reduces neuroinflammation, normalizes membrane expression of glutamate and GABA receptors, and restores spatial learning in hyperammonemic rats. CONCLUSIONS: Hyperammonemia-induced neuroinflammation impairs glutamatergic and GABAergic neurotransmission by altering membrane expression of glutamate and GABA receptors, resulting in impaired spatial learning. Sulforaphane reverses all these effects. Treatment with sulforaphane could be useful to improve cognitive function in cirrhotic patients with minimal or clinical hepatic encephalopathy. PMID- 26883216 TI - Aesthetic Patient-Centric Approach to a Unilateral Zygomaticomaxillary Fracture: Computer-Guided Osteotomy of the Non-Injured Side. PMID- 26883217 TI - Objective Sensory Changes Following Subfascial Breast Augmentation. AB - BACKGROUND: Sensory changes occur following breast augmentation, and describing the incidence, pattern, and course of deficit is important for informed consent. OBJECTIVES: To examine sensory changes following subfascial breast augmentation, and the influence of change in breast volume caused by an implant. METHODS: One hundred and sixty-two consecutive patients undergoing subfascial breast augmentation were assessed for sensory changes using a Semmes Weinstein monofilament test before surgery, 2, 6, and 12 weeks postoperatively. Morphometric measurements allowed a breast volume to be calculated and the percentage change in volume produced by the implant. RESULTS: Most women (92.5%) regained preoperative levels of sensation in all areas of the breast, excepting the lower-outer quadrants (16.15%) by 12 weeks following surgery. Four percent of nipple-areolar complexes (NAC) failed return to preoperative levels of sensitivity by 12 weeks after surgery. Younger patients or those who have a high BMI and a measurably thicker soft tissue envelope were more likely to experience sensory deficits. Breast augmentation in this series produced calculated volume changes by an implant of between 12.1% and 102.7%. Within these limits there is no association between percentage increase in breast volume and sensory deficits. CONCLUSIONS: The study demonstrates that for calculated volume increases of up to 102% of the initial breast volume, sensory loss at 12 weeks after surgery is 4% at the NAC. The commonest area of diminished sensitivity is the lower-outer quadrant (16.15%), relating to the use of the inframammary crease incision. It provides a useful adjunct in monitoring patient recovery following subfascial breast augmentation. LEVEL OF EVIDENCE 4: Therapeutic. PMID- 26883218 TI - Response to "Commentary on: Microbiologic Safety of the Transareolar Approach in Breast Augmentation". PMID- 26883219 TI - Modeling correlates of low bone mineral density in patients with phenylalanine hydroxylase deficiency. AB - Phenylalanine hydroxylase (PAH) deficiency is an inherited metabolic disorder requiring life-long restriction of dietary protein and phenylalanine-free medical food. Low bone mineral density (BMD) is reported, but factors associated with BMD Z-score (standard deviations from normal) are unknown. We examined associations between clinical and dietary parameters and total BMD Z-score in PAH deficiency patients, and developed models to predict Z-score. Data collected from patients >4 years of age (n = 88; mean age = 18.8 y; 61 % female) included demographic, clinical, laboratory, and dietary intakes. Adjusted Spearman's correlation coefficients were calculated between parameters and TBMD Z-score, measured by dual energy x-ray absorptiometry (DXA). Parameters approaching significance (p value < 0.10) were candidate predictors for four linear regression models predicting TBMD Z-score. To validate, model-predicted Z-scores were compared to DXA Z-scores. Mean TBMD Z-score was -0.326; 18 (20.4 %) had Z-score < -1. Z scores were positively correlated with dietary vitamin D, calcium, and medical food intake and compliance with prescription, and negatively with dietary carbohydrate, sugar, caffeine intake, glycemic load, and prescribed medical food (grams protein/day; p-value < 0.05). The best model included medical food compliance, medical food intake, caffeine intake, and bone-specific alkaline phosphatase (r-square = 0.364). This model predicted Z-score category [normal or low (<-1)] with sensitivity = 66.7 %, likelihood ratio = 14.7, and AUC = 0.83 compared to DXA Z-score. No subjects had low BMD for chronological age (Z-score <= -2). Compliance with medical food prescription was the strongest predictor of TBMD Z-score. One model, if validated in a separate sample of patients with more cases of low BMD, showed potential to estimate TBMD Z-score using routine clinical patient parameters. PMID- 26883220 TI - The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders. AB - In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved in the development of anti-drug antibodies and the current therapies used in their treatment. Given the current understanding of the adaptive immune response, it focuses particularly on T cell dependent mechanisms and the paradigm of using lymphocytic negative selection as a predictor of antibody formation. This concept originally postulated in the 1970s, stipulated that the genotypically determined lack of production or production of a variant protein determines an individual's lymphocytic repertoire. This in turn is the key factor in determining the potential severity of an individual's immunological response to ERT. It also highlights the need for immunological assay standardization particularly those looking at describing the degree of functional impact, robust biochemical or clinical endpoints and detailed patient subgroup identification if the true evaluations of impact are to be realised. PMID- 26883221 TI - Unreduced gamete formation in wheat * Aegilops spp. hybrids is genotype specific and prevented by shared homologous subgenomes. AB - KEY MESSAGE: The presence of homologous subgenomes inhibited unreduced gamete formation in wheat * Aegilops interspecific hybrids. Unreduced gamete rates were under the control of the wheat nuclear genome. Production of unreduced gametes is common among interspecific hybrids, and may be affected by parental genotypes and genomic similarity. In the present study, five cultivars of Triticum aestivum and two tetraploid Aegilops species (i.e. Ae. triuncialis and Ae. cylindrica) were reciprocally crossed to produce 20 interspecific hybrid combinations. These hybrids comprised two different types: T. aestivum * Aegilops triuncialis; 2n = ABDU(t)C(t) (which lack a common subgenome) and T. aestivum * Ae. cylindrica; 2n = ABDD(c)C(c) (which share a common subgenome). The frequency of unreduced gametes in F1 hybrids was estimated in sporads from the frequency of dyads, and the frequency of viable pollen, germinated pollen and seed set were recorded. Different meiotic abnormalities recorded in the hybrids included precocious chromosome migration to the poles at metaphase I and II, laggards in anaphase I and II, micronuclei and chromosome stickiness, failure in cell wall formation, premature cytokinesis and microspore fusion. The mean frequency of restitution meiosis was 10.1 %, and the mean frequency of unreduced viable pollen was 4.84 % in T. aestivum * Ae. triuncialis hybrids. By contrast, in T. aestivum * Ae. cylindrica hybrids no meiotic restitution was observed, and a low rate of viable gametes (0.3 %) was recorded. This study present evidence that high levels of homologous pairing between the D and D(c) subgenomes may interfere with meiotic restitution and the formation of unreduced gametes. Variation in unreduced gamete production was also observed between T. aestivum * Ae. triuncialis hybrid plants, suggesting genetic control of this trait. PMID- 26883222 TI - Regulation of plant reactive oxygen species (ROS) in stress responses: learning from AtRBOHD. AB - Reactive oxygen species (ROS) are constantly produced in plants, as the metabolic by-products or as the signaling components in stress responses. High levels of ROS are harmful to plants. In contrast, ROS play important roles in plant physiology, including abiotic and biotic tolerance, development, and cellular signaling. Therefore, ROS production needs to be tightly regulated to balance their function. Respiratory burst oxidase homologue (RBOH) proteins, also known as plant nicotinamide adenine dinucleotide phosphate oxidases, are well studied enzymatic ROS-generating systems in plants. The regulatory mechanisms of RBOH dependent ROS production in stress responses have been intensively studied. This has greatly advanced our knowledge of the mechanisms that regulate plant ROS production. This review attempts to integrate the regulatory mechanisms of RBOHD dependent ROS production by discussing the recent advance. AtRBOHD-dependent ROS production could provide a valuable reference for studying ROS production in plant stress responses. PMID- 26883223 TI - Assessment of ptxD gene as an alternative selectable marker for Agrobacterium mediated maize transformation. AB - KEY MESSAGE: Bacterial phosphite oxidoreductase gene and chemical phosphite can be used as a selection system for Agrobacterium -mediated maize transformation. Application of phosphite (Phi) on plants can interfere the plant metabolic system leading to stunted growth and lethality. On the other hand, ectopic expression of the ptxD gene in tobacco and Arabidopsis allowed plants to grow in media with Phi as the sole phosphorous source. The phosphite oxidoreductase (PTXD) enzyme catalyzes the conversion of Phi into phosphate (Pi) that can then be metabolized by plants and utilized as their essential phosphorous source. Here we assess an alternative selectable marker based on a bacterial ptxD gene for Agrobacterium mediated maize transformation. We compared the transformation frequencies of maize using either the ptxD/Phi selection system or a standard herbicide bar/bialaphos selection system. Two maize genotypes, a transformation amenable hybrid Hi II and an inbred B104, were tested. Transgene presence, insertion copy numbers, and ptxD transcript levels were analyzed and compared. This work demonstrates that the ptxD/Phi selection system can be used for Agrobacterium mediated maize transformation of both type I and type II callus culture and achieve a comparable frequency as that of the herbicide bar/bialaphos selection system. PMID- 26883224 TI - A mutation of casein kinase 2 alpha4 subunit affects multiple developmental processes in Arabidopsis. AB - KEY MESSAGE: Arabidopsis CK2 alpha4 subunit regulates the primary root and hypocotyl elongation, lateral root formation, cotyledon expansion, rosette leaf initiation and growth, flowering, and anthocyanin biosynthesis. Casein kinase 2 (CK2) is a conserved tetrameric kinase composed of two alpha and two beta subunits. The inhibition of CK2 activity usually results in severe developmental deficiency. Four genes (CKA1-CKA4) encode CK2 alpha subunit in Arabidopsis. Single mutations of CKA1, CKA2, and CKA3 do not affect the normal growth of Arabidopsis, while the cka1 cka2 cka3 triple mutants are defective in cotyledon and hypocotyl growth, lateral root development, and flowering. The inhibition of CKA4 expression in cka1 cka2 cka3 background further reduces the number of lateral roots and delays the flowering time. Here, we report the characterization of a novel knockout mutant of CKA4, which exhibits various developmental defects including reduced primary root and hypocotyl elongation, increased lateral root density, delayed cotyledon expansion, retarded rosette leaf initiation and growth, and late flowering. The examination of the cellular basis for abnormal root development of this mutant revealed reduced root meristem cells with enhanced RETINOBLASTOMA-RELATED (RBR) expression that promotes cell differentiation in root meristem. Moreover, this cka4-2 mutant accumulates higher anthocyanin in the aerial part and shows an increased expression of anthocyanin biosynthetic genes, suggesting a novel role of CK2 in modulating anthocyanin biosynthesis. In addition, the complementation test using primary root elongation assay as a sample confirms that the changed phenotypes of this cka4-2 mutant are due to the lack of CKA4. Taken together, this study reveals an essential role of CK2 alpha4 subunit in multiple developmental processes in Arabidopsis. PMID- 26883225 TI - Physiological controls of chrysanthemum DgD27 gene expression in regulation of shoot branching. AB - KEY MESSAGE: DgD27 was cloned from D. grandiflorum for the first time and played an important role in shoot branching of chrysanthemum. Shoot branching plays an important role in determining plant architecture. D27 was previously proven to be involved in the strigolactone biosynthetic pathway in rice, Arabidopsis, and Medicago. To investigate the role of D27 in shoot branching of chrysanthemum, we isolated the D27 homolog DgD27. Functional analysis showed that DgD27 was a plastid-localized protein that restored the phenotype of Arabidopsis d27-1. Gene expression analysis revealed that DgD27 was expressed at the highest levels in stem, and was up-regulated by exogenous auxin. Decapitation could down-regulate DgD27 expression, but this effect could be restored by exogenous auxin. DgD27 expression was significantly down-regulated by dark treatment in axillary buds. In addition, DgD27 transcripts produced rapid responses in shoots and roots under conditions of phosphate absence, but only mild variation in responses in buds, stems, and roots with low nitrogen treatment. DgBRC1 transcripts also showed the same response in buds under low nitrogen conditions. Under phosphate deficiency, indole-3-acetic acid (IAA) levels increased, zeatin riboside levels decreased, and abscisic acid (ABA) levels increased in the shoot, while both IAA and ABA levels increased in the shoot under low nitrogen treatments. Gibberellin acid levels were unaffected by phosphate deficiency and low nitrogen treatments. Taken together, these results demonstrated the diverse roles of DgD27 in response to physiological controls in chrysanthemum shoot branching. PMID- 26883226 TI - Magnaporthe oryzae effectors MoHEG13 and MoHEG16 interfere with host infection and MoHEG13 counteracts cell death caused by Magnaporthe-NLPs in tobacco. AB - KEY MESSAGE: Adapted pathogens are able to modulate cell responses of their hosts most likely due to the activity of secreted effector molecules thereby enabling colonisation by ostensible nonhost pathogens. It is postulated that host and nonhost pathogens of a given plant species differ in their repertoire of secreted effector molecules that are able to suppress plant resistance. We pursued the strategy of identifying novel effectors of Magnaporthe oryzae, the causal agent of blast disease, by comparing the infection process of closely related host vs. nonhost Magnaporthe species on barley (Hordeum vulgare L.). When both types of pathogen simultaneously attacked the same cell, the nonhost isolate became a successful pathogen possibly due to potent effectors secreted by the host isolate. Microarray studies led to a set of M. oryzae Hypothetical Effector Genes (MoHEGs) which were classified as Early- and LateMoHEGs according to the maximal transcript abundance during colonization of barley. Interestingly, orthologs of these MoHEGs from a nonhost pathogen were similarly regulated when investigated in a host situation, suggesting evolutionary conserved functions. Knockout mutants of MoHEG16 from the group of EarlyMoHEGs were less virulent on barley and microscopic studies revealed an attenuated transition from epidermal to mesophyll colonization. MoHEG13, a LateMoHEG, was shown to antagonize cell death induced by M. oryzae Necrosis-and ethylene-inducing-protein-1 (Nep1)-like proteins in Nicotiana benthamiana. MoHEG13 has a virulence function as a knockout mutant showed attenuated disease progression when inoculated on barley. PMID- 26883227 TI - mRNA biogenesis-related helicase eIF4AIII from Arabidopsis thaliana is an important factor for abiotic stress adaptation. AB - Similar to other plant species, Arabidopsis has a huge repertoire of predicted helicases, including the eIF4AIII factor, a putative component of the exon junction complex related to mRNA biogenesis. In this article, we integrated evolutionary and functional approaches to have a better understanding of eIF4AIII function in plants. Phylogenetic analysis showed that the mRNA biogenesis-related helicase eIF4AIII is the ortholog of the stress-related helicases PDH45 from Pisum sativum and MH1 from Medicago sativa, suggesting evolutionary and probably functional equivalences between mRNA biogenesis and stress-related plant helicases. Molecular and genetic analyses confirmed the relevance of eIF4AIII during abiotic stress adaptation in Arabidopsis. Therefore, in addition to its function in mRNA biogenesis, eIF4AIII can play a role in abiotic stress adaptation. PMID- 26883228 TI - Seasonal-based temporal changes fluctuate expression patterns of TXS, DBAT, BAPT and DBTNBT genes alongside production of associated taxanes in Taxus baccata. AB - KEY MESSAGE: Environmental cues have synergistic or antagonistic regulatory roles on transcription activity and taxanes accumulation in yew, though DBAT activity is less influenced, could be accordingly a rate-limiting enzyme. The current work was undertaken to elucidate the consequences of some environmental cues (i.e., day length, temperature, sunlight and relative humidity) on the expression patterns of TXS, DBAT, BAPT and DBTNBT genes contributed to the taxol biosynthetic pathway along with the accumulation of some taxanes in needles and stems of Taxus baccata over year 2013-2014. In both tissues, light intensity and temperature correlated with the production of 10-DAB III and total taxanes, and TXS activity, while a lack of significant association was deduced for day length and relative humidity. Furthermore, in both tissues, a weak correlation was observed between BAC III and light intensity, temperature, day length and relative humidity, and the corresponding gene, DBAT. Surprisingly, DBAT activity was not co-induced with TXS in both tissues, and remained expressed at basal levels over year, supporting that the conversion of 10-DAB III into BAC III could presumably be a rate limiting step in the taxol biosynthetic pathway. Similar to BAC III, no strong correlation was detected between production of taxol in both tissues and all the meteorological data, while the corresponding genes BAPT and DBTNBT, in some cases, exhibited significant correlated results. Notably, despite higher activities of BAPT and DBTNBT in both tissues over year, taxol production was still in small quantities, probably owing to the low amounts of its precursors rather than low volumes of BAPT and DBTNBT transcripts. The results, altogether, could provide us new insights towards the potential regulatory roles of environmental cues on the production of taxanes in yew trees. PMID- 26883229 TI - "Wake Up! HIV is at Your Door": African American Faith Leaders in the Rural South and HIV Perceptions: A Qualitative Analysis. AB - In Alabama, 70 % of new HIV cases are among African Americans. Because the Black Church plays an important role for many African Americans in the south, we conducted qualitative interviews with 10 African American pastors recruited for an HIV intervention study in rural Alabama. Two main themes emerged: (1) HIV stigma is prevalent and (2) the role of the Black Church in addressing HIV in the African American community. Our data suggest that pastors in rural Alabama are willing to be engaged in HIV prevention solutions; more formalized training is needed to decrease stigma, strengthen HIV prevention and support persons living with HIV/AIDS. PMID- 26883230 TI - Potential causes for obtaining non-diagnostic results from fine needle aspiration biopsy of thyroid nodules. AB - PURPOSE: The aim of this prospective study was to evaluate factors that could affect the diagnostic result success ratio of fine needle aspiration biopsy of thyroid nodules. MATERIALS AND METHODS: 664 patients and 696 nodules were included in this study. Demographic features of age and gender and nodule features of macrocalcification (MC) and internal content (cystic or solid predominance) were evaluated. All biopsies were performed from 1 cm or larger nodules. Three different size needles were used for comparison (22, 23 and 25 G). The patients in each group had a similar number of nodules with MC, and cystic predominance to obtain comparable results. All procedures were performed by the same radiologist, who had 4 years of experience. Histologically adequate material criteria were identified. All pathological specimens were evaluated as diagnostic or non-diagnostic by the same pathology technician. Chi-square, student's t test and univariate analysis were used for statistical analysis. RESULTS: There were no statistically significant differences in demographic features and nodule properties from diagnostic results of fine needle aspiration biopsy of thyroid nodules. On the other hand, 23 G needles offered a better potential for obtaining adequate samples with a statistically significant difference. CONCLUSION: Obtaining adequate material in fine needle aspiration biopsy from thyroid nodules is a challenging issue and the results are controversial. Since we obtained the best ratio with 23 G needles, we recommend interventional radiologists to use 23 G needles as far as possible and not to consider needles thicker needles than 22 G or thinner than 25 G. Nodule features and demographic features did not have an effect on obtaining adequate cytological material. PMID- 26883231 TI - ePTFE stent graft in non-steno-occlusive arterial disease: 2 centers retrospective study. AB - PURPOSE: We report our experience regarding use of Fluency stent graft (Bard, Murray Hill, NJ, USA) for the treatment of peripheral aneurysms, pseudoaneurysms, arteriovenous fistulae, dissections and arterial ruptures, lacerations or perforations. METHODS AND MATERIALS: This two-center study included 59 patients (40 M, 19 F) with a mean age of 64.37 years (range 20-91 years). In total 61 lesions were treated, so subdivided: 10 true aneurysms, 26 pseudoaneurysms, 5 iatrogenic arteriovenous fistulae, 20 arterial ruptures, lacerations or perforations. RESULTS: Immediate technical success was obtained in 60 of 61 lesions (98.3 %); in 1 case (pseudoaneurysm of hepatic artery) additional embolization of the gastroduodenal artery with microcoils was needed. Follow-up was available for 57 patients and 59 lesions; mean period was 23.52 months (range 1-60 months). At 1-year primary patency was 89.47 %, whereas secondary patency was 96.4 %. CONCLUSION: Endovascular application of Fluency stent graft seems to offer an effective, and durable less invasive alternative to standard surgical techniques for the treatment of peripheral aneurysms, pseudoaneurysms, iatrogenic arteriovenous fistulae and arterial ruptures, or penetrating injuries. PMID- 26883232 TI - Percutaneous alcohol injection under sonographic guidance in Morton's neuroma: follow-up in 220 treated lesions. AB - PURPOSE: To evaluate the efficacy and safety of percutaneous treatment of Civinini-Morton's syndrome due to solitary Morton's neuroma and analyze the effect of clinico-demographic factors on outcome. MATERIALS AND METHODS: Alcohol injection was performed under sonographic guidance in 220 consecutive patients. Pain intensity using a numerical rating scale (NRS), pain features, limitation of everyday activities and comorbidity with other forefoot conditions were evaluated at presentation. Patients were reassessed for symptoms and the need of rescue therapy with neurectomy after a mean follow-up of 19.0 months (range 15-24). RESULTS: We treated 220 patients (33 males, mean age 55.8 years). Neuromas were located in the III intermetatarsal space in 85.5 %, with a mean size of 5.4 mm. When considering a reduction of pain intensity of >=50 % of NRS or a complete disappearance of the neuropathic features as a satisfactory clinical response, a 72.3 % (p < 0.001) responder rate was obtained, and only three patients relapsed (1.2 %). An improvement in limitation of everyday activities was observed in 88.6 % (p < 0.001). No influence of clinico-demographic variables on outcome was found. No major complications occurred. Patients with unsatisfactory response had an overload-related comorbid condition in 20/61 (32.8 %). Surgery was later performed in 14 non-responder patients. CONCLUSIONS: Ultrasound-guided alcoholization demonstrated a safe profile, relieved neuropathic symptoms in a majority of patients and improved their quality of life. Rescue therapy with surgery is feasible in patients with unsatisfactory response. However, a thorough evaluation for forefoot comorbidities should be obtained, as they may act as confounding factors. PMID- 26883233 TI - Good-quality social care for people with Parkinson's disease: a qualitative study. AB - OBJECTIVES: The study examines the meaning of good-quality social care for people with Parkinson's disease and their carers. It identifies, from their perspective, the impact of good-quality social care on health and well-being. DESIGN: Qualitative case study methodology, interview and framework analysis techniques were used. SETTING: community locations in the north and midlands of England. PARTICIPANTS: Data were collected from 43 participants including individual interviews with people with Parkinson's disease (n=4), formal and informal social care providers (n=13), 2 focus groups, 1 with people with Parkinson's disease and their carers (n=17), and 1 with professionals (n=8), plus a telephone interview with a former commissioner. FINDINGS: Good-quality social care, delivered in a timely fashion, was reported to have a positive impact on health. Furthermore, there is an indication that good-quality social care can prevent untoward events, such as infections, symptom deterioration and deterioration in mental health. The concept of the 'Impact Gap' developed from the findings, illustrates how the costs of care may be reduced by delivering good-quality social care. Control, choice and maintaining independence emerged as indicators of good-quality social care, irrespective of clinical condition. Participants identified characteristics indicative of good-quality social care specific to Parkinson's disease, including understanding Parkinson's disease, appropriate administration of medication, timing of care and reassessment. 'Parkinson's aware' social care was seen to generate psychological, physical and social benefits that were inter-related. CONCLUSIONS: The findings indicate how maximising quality in social care delivery for people with Parkinson's disease can impact on health and well-being. Long term or short-term benefits may result in prevented events and reductions in health and social care resource. Health professionals can be instrumental in early detection of and signposting to social care. PMID- 26883234 TI - Surgical complications and their impact on patients' psychosocial well-being: a systematic review and meta-analysis. AB - OBJECTIVE: Surgical complications may affect patients psychologically due to challenges such as prolonged recovery or long-lasting disability. Psychological distress could further delay patients' recovery as stress delays wound healing and compromises immunity. This review investigates whether surgical complications adversely affect patients' postoperative well-being and the duration of this impact. METHODS: The primary data sources were 'PsychINFO', 'EMBASE' and 'MEDLINE' through OvidSP (year 2000 to May 2012). The reference lists of eligible articles were also reviewed. Studies were eligible if they measured the association of complications after major surgery from 4 surgical specialties (ie, cardiac, thoracic, gastrointestinal and vascular) with adult patients' postoperative psychosocial outcomes using validated tools or psychological assessment. 13,605 articles were identified. 2 researchers independently extracted information from the included articles on study aims, participants' characteristics, study design, surgical procedures, surgical complications, psychosocial outcomes and findings. The studies were synthesised narratively (ie, using text). Supplementary meta-analyses of the impact of surgical complications on psychosocial outcomes were also conducted. RESULTS: 50 studies were included in the narrative synthesis. Two-thirds of the studies found that patients who suffered surgical complications had significantly worse postoperative psychosocial outcomes even after controlling for preoperative psychosocial outcomes, clinical and demographic factors. Half of the studies with significant findings reported significant adverse effects of complications on patient psychosocial outcomes at 12 months (or more) postsurgery. 3 supplementary meta analyses were completed, 1 on anxiety (including 2 studies) and 2 on physical and mental quality of life (including 3 studies). The latter indicated statistically significantly lower physical and mental quality of life (p<0.001) for patients who suffered surgical complications. CONCLUSIONS: Surgical complications appear to be a significant and often long-term predictor of patient postoperative psychosocial outcomes. The results highlight the importance of attending to patients' psychological needs in the aftermath of surgical complications. PMID- 26883235 TI - Using kernel density estimation to understand the influence of neighbourhood destinations on BMI. AB - OBJECTIVES: Little is known about how the distribution of destinations in the local neighbourhood is related to body mass index (BMI). Kernel density estimation (KDE) is a spatial analysis technique that accounts for the location of features relative to each other. Using KDE, this study investigated whether individuals living near destinations (shops and service facilities) that are more intensely distributed rather than dispersed, have lower BMIs. STUDY DESIGN AND SETTING: A cross-sectional study of 2349 residents of 50 urban areas in metropolitan Melbourne, Australia. METHODS: Destinations were geocoded, and kernel density estimates of destination intensity were created using kernels of 400, 800 and 1200 m. Using multilevel linear regression, the association between destination intensity (classified in quintiles Q1(least)-Q5(most)) and BMI was estimated in models that adjusted for the following confounders: age, sex, country of birth, education, dominant household occupation, household type, disability/injury and area disadvantage. Separate models included a physical activity variable. RESULTS: For kernels of 800 and 1200 m, there was an inverse relationship between BMI and more intensely distributed destinations (compared to areas with least destination intensity). Effects were significant at 1200 m: Q4, beta -0.86, 95% CI -1.58 to -0.13, p=0.022; Q5, beta -1.03 95% CI -1.65 to -0.41, p=0.001. Inclusion of physical activity in the models attenuated effects, although effects remained marginally significant for Q5 at 1200 m: beta -0.77 95% CI -1.52, -0.02, p=0.045. CONCLUSIONS: This study conducted within urban Melbourne, Australia, found that participants living in areas of greater destination intensity within 1200 m of home had lower BMIs. Effects were partly explained by physical activity. The results suggest that increasing the intensity of destination distribution could reduce BMI levels by encouraging higher levels of physical activity. PMID- 26883236 TI - Thigh length versus knee length antiembolism stockings for the prevention of deep vein thrombosis in postoperative surgical patients; a systematic review and network meta-analysis. AB - OBJECTIVES: To assess the clinical effectiveness of thigh length versus knee length antiembolism stockings for the prevention of deep vein thrombosis (DVT) in surgical patients. DESIGN: Systematic review and meta-analysis using direct methods and network meta-analysis. METHODS: Previous systematic reviews and electronic databases were searched to February 2014 for randomised controlled trials (RCTs) of thigh length or knee length antiembolism stockings in surgical patients. Study quality was assessed using the Cochrane Risk of Bias Tool. The primary outcome was incidence of DVT. Analysis of the DVT data was performed using ORs along with 95% CIs. The I(2) statistic was used to quantify statistical heterogeneity. RESULTS: 23 RCTs were included; there was substantial variation between the trials and many were poorly reported with an unclear risk of bias. Five RCTs directly comparing thigh length versus knee length stockings were pooled and the summary estimate of effect favouring thigh length stockings was not statistically significant (OR 1.48, 95% CI 0.80 to 2.73). 13 RCTs were included in the network meta-analysis; thigh length stockings with pharmacological prophylaxis were more effective than knee length stockings with pharmacological prophylaxis, but again results were not statistically significant (OR 1.76, 95% credible intervals 0.82 to 3.53). CONCLUSIONS: Thigh length stockings may be more effective than knee length stockings, but results did not reach statistical significance and the evidence base is weak. Further research to confirm this finding is unlikely to be worthwhile. While thigh length stockings appear to have superior efficacy, practical issues such as patient acceptability may prevent their wide use in clinical practice. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014007202. PMID- 26883237 TI - Seasonal influenza vaccination delivery through community pharmacists in England: evaluation of the London pilot. AB - OBJECTIVE: To evaluate the effectiveness and cost of the pan-London pharmacy initiative, a programme that allows administration of seasonal influenza vaccination to eligible patients at pharmacies. DESIGN: We analysed 2013-2015 data on vaccination uptake in pharmacies via the Sonar reporting system, and the total vaccination uptake via 2011-2015 ImmForm general practitioner (GP) reporting system data. We conducted an online survey of London pharmacists who participate in the programme to assess time use data, vaccine choice, investment costs and opinions about the programme. We conducted an online survey of London GPs to assess vaccine choice of vaccine and opinions about the pharmacy vaccine delivery programme. SETTING: All London boroughs. PARTICIPANTS: London-based GPs, and pharmacies that currently offer seasonal flu vaccination. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Comparison of annual vaccine uptake in London across risk groups from years before pharmacy vaccination introduction to after pharmacy vaccination introduction. Completeness of vaccine uptake reporting data. Cost to the National Health Service (NHS) of flu vaccine delivery at pharmacies with that at GPs. Cost to pharmacists of flu delivery. Opinions of pharmacists and GPs regarding the flu vaccine pharmacy initiative. RESULTS: No significant change in the uptake of seasonal vaccination in any of the risk groups as a result of the pharmacy initiative. While on average a pharmacy-administered flu vaccine dose costs the NHS up to L2.35 less than a dose administered at a GP, a comparison of the 2 recording systems suggests there is substantial loss of data. CONCLUSIONS: Flu vaccine delivery through pharmacies shows potential for improving convenience for vaccine recipients. However, there is no evidence that vaccination uptake increases and the use of 2 separate recording systems leads to time-consuming data entry and missing vaccine record data. PMID- 26883238 TI - Rates of self-harm presenting to general hospitals: a comparison of data from the Multicentre Study of Self-Harm in England and Hospital Episode Statistics. AB - OBJECTIVE: Rates of hospital presentation for self-harm in England were compared using different national and local data sources. DESIGN: The study was descriptive and compared bespoke data collection methods for recording self-harm presentations to hospital with routinely collected hospital data. SETTING: Local area data on self-harm from the 3 centres of the Multicentre Study of Self-harm in England (Oxford, Manchester and Derby) were used along with national and local routinely collected data on self-harm admissions and emergency department attendances from Hospital Episode Statistics (HES). PRIMARY OUTCOME: Rate ratios were calculated to compare rates of self-harm generated using different data sources nationally and locally (between 2010 and 2012) and rates of hospital presentations for self-harm were plotted over time (between 2003 and 2012), based on different data sources. RESULTS: The total number of self-harm episodes between 2010 and 2012 was 13,547 based on Multicentre Study data, 9600 based on HES emergency department data and 8096 based on HES admission data. Nationally, routine HES data underestimated overall rates of self-harm by approximately 60% compared with rates based on Multicentre Study data (rate ratio for HES emergency department data, 0.41 (95% CI 0.35 to 0.49); rate ratio for HES admission data, 0.42 (95% CI 0.36 to 0.49)). Direct local area comparisons confirmed an overall underascertainment in the HES data, although the difference varied between centres. There was a general increase in self-harm over time according to HES data which contrasted with a fall and then a rise in the Multicentre Study data. CONCLUSIONS: There was a consistent underestimation of presentations for self harm recorded by HES emergency department data, and fluctuations in year-on-year figures. HES admission data appeared more reliable but missed non-admitted episodes. Routinely collected data may miss important trends in self-harm and cannot be used in isolation as the basis for a robust national indicator of self harm. PMID- 26883239 TI - Social group memberships in retirement are associated with reduced risk of premature death: evidence from a longitudinal cohort study. AB - OBJECTIVES: Retirement constitutes a major life transition that poses significant challenges to health, with many retirees experiencing a precipitous decline in health status following retirement. We examine the extent to which membership in social groups following retirement determines quality of life and mortality. DESIGN: The longitudinal impact of the number of social group memberships before and after the transition to retirement was assessed on retirees' quality of life and risk of death 6 years later. SETTING: Nationally representative cohort study of older adults living in England. PARTICIPANTS: Adults who underwent the transition to retirement (N=424). A matched control group (N=424) of participants who had comparable demographic and health characteristics at baseline but did not undergo the transition to retirement were also examined. OUTCOME MEASURES: Analyses examined participants' quality of life and mortality during a period of 6 years. RESULTS: Retirees who had two group memberships prior to retirement had a 2% risk of death in the first 6 years of retirement if they maintained membership in two groups, a 5% risk if they lost one group and a 12% risk if they lost both groups. Furthermore, for every group membership that participants lost in the year following retirement, their experienced quality of life 6 years later was approximately 10% lower. These relationships are robust when controlling for key sociodemographic variables (age, gender, relationship status and socioeconomic status prior to retirement). A comparison with a matched control group confirmed that these effects were specific to those undergoing the transition to retirement. The effect of social group memberships on mortality was comparable to that of physical exercise. CONCLUSIONS: Theoretical implications for our understanding of the determinants of retiree quality of life and health, and practical implications for the support of people transitioning from a life of work to retirement are discussed. PMID- 26883240 TI - Impact of visual acuity on developing literacy at age 4-5 years: a cohort-nested cross-sectional study. AB - OBJECTIVES: To estimate the prevalence of poor vision in children aged 4-5 years and determine the impact of visual acuity on literacy. DESIGN: Cross-sectional study linking clinical, epidemiological and education data. SETTING: Schools located in the city of Bradford, UK. PARTICIPANTS: Prevalence was determined for 11,186 children participating in the Bradford school vision screening programme. Data linkage was undertaken for 5836 Born in Bradford (BiB) birth cohort study children participating both in the Bradford vision screening programme and the BiB Starting Schools Programme. 2025 children had complete data and were included in the multivariable analyses. MAIN OUTCOME MEASURES: Visual acuity was measured using a logMAR Crowded Test (higher scores=poorer visual acuity). Literacy measured by Woodcock Reading Mastery Tests-Revised (WRMT-R) subtest: letter identification (standardised). RESULTS: The mean (SD) presenting visual acuity was 0.14 (0.09) logMAR (range 0.0-1.0). 9% of children had a presenting visual acuity worse than 0.2logMAR (failed vision screening), 4% worse than 0.3logMAR (poor visual acuity) and 2% worse than 0.4logMAR (visually impaired). Unadjusted analysis showed that the literacy score was associated with presenting visual acuity, reducing by 2.4 points for every 1 line (0.10logMAR) reduction in vision (95% CI -3.0 to -1.9). The association of presenting visual acuity with the literacy score remained significant after adjustment for demographic and socioeconomic factors reducing by 1.7 points (95% CI -2.2 to -1.1) for every 1 line reduction in vision. CONCLUSIONS: Prevalence of decreased visual acuity was high compared with other population-based studies. Decreased visual acuity at school entry is associated with reduced literacy. This may have important implications for the children's future educational, health and social outcomes. PMID- 26883241 TI - Impact of conflict on medical education: a cross-sectional survey of students and institutions in Iraq. AB - OBJECTIVE: This study surveyed all Iraqi medical schools and a cross-section of Iraqi medical students regarding their institutional and student experiences of medical education amidst ongoing conflict. The objective was to better understand the current resources and challenges facing medical schools, and the impacts of conflict on the training landscape and student experience, to provide evidence for further research and policy development. SETTING: Deans of all Iraqi medical schools registered in the World Directory of Medical Schools were invited to participate in a survey electronically. Medical students from three Iraqi medical schools were invited to participate in a survey electronically. OUTCOMES: Primary: Student enrolment and graduation statistics; human resources of medical schools; dean perspectives on impact of conflict. Secondary: Medical student perspectives on quality of teaching, welfare and future career intentions. FINDINGS: Of 24 medical schools listed in the World Directory of Medical Schools, 15 replied to an initial email sent to confirm their contact details, and 8 medical schools responded to our survey, giving a response rate from contactable medical schools of 53% and overall of 33%. Five (63%) medical schools reported medical student educational attainment being impaired or significantly impaired; 4 (50%) felt the quality of training medical schools could offer had been impaired or significantly impaired due to conflict. A total of 197 medical students responded, 62% of whom felt their safety had been threatened due to violent insecurity. The majority (56%) of medical students intended to leave Iraq after graduating. CONCLUSIONS: Medical schools are facing challenges in staff recruitment and adequate resource provision; the majority believe quality of training has suffered as a result. Medical students are experiencing added psychological stress and lower quality of teaching; the majority intend to leave Iraq after graduation. PMID- 26883242 TI - The Aldosterone Renin Ratio (ARR) APP as Tool to Enhance the Detection Rate of Primary Aldosteronism. AB - Primary aldosteronism is one of the most common forms of secondary hypertension, but it is often under diagnosed, which leads to the development of cardiovascular damage, and excess costs for long-term drug treatment and management of complications. The aldosterone to renin ratio (ARR) is a key step for early detection of primary aldosteronism, but unfortunately is not easily estimated. This is because plasma aldosterone and renin are measured with different assays, which provide results in different units of measure, with ensuing difficulty of obtaining the calculation of the ARR in the proper units and impossibility of interpreting results with reference to established cut off values. Therefore, doctors are often unable to draw unambiguous conclusions to be used for the clinical decision-making. To the aim of making the diagnostic work-up easier, we have developed an Application that provide a swift calculation of the ARR regardless of the units of measure used for plasma aldosterone and renin values. If the concomitant serum potassium level is available the App also provides the patient's probability of having an aldosterone-producing adenoma based on a validated logistic discriminant analysis. PMID- 26883243 TI - Effect of hypovolemia on efficacy of reflex maintenance of blood pressure on orthostatic challenge. AB - INTRODUCTION: Blood volume is an important determinant of the efficacy of the negative feedback mechanisms that maintain blood pressure. However, its effect on time profile and magnitude of the responses remain unstudied. AIM: To study the effect of mild hypovolemia on time profiles and magnitude of changes in blood pressure and heart rate in healthy subjects before and after blood donation. METHODS: Fifty six healthy volunteer donors who signed up for blood donation were recruited (age 35 +/- 7 years; weight 75 +/- 9 Kg). Baseline beat to beat blood pressure and Lead II ECG was recorded for 5 min followed by orthostatic challenge for 3 min before and after blood donation. RESULTS: The donation of 450 ml of blood did not lead to any changes in the resting systolic, diastolic or mean blood pressure. However, there was a significant decrease in pulse pressure after blood donation along with an increase in the heart rate. During orthostatic challenge, after blood donation there was a greater fall in systolic, diastolic, mean and pulse pressure along with a greater increase in heart rate as compared to before the blood donation. The latency to response and the total time to recovery of blood pressure and heart rate increased significantly after blood donation. CONCLUSION: Maintenance of blood pressure after orthostatic challenge is not compromised after mild hypovolemia produced by donation of 450 ml of blood. However, mild hypovolemia results in increase in latency of response and is accompanied with larger magnitude of fall in blood pressure during orthostatic challenge. PMID- 26883244 TI - Is it important to consider the sex of the patient when using lithium or valproate to treat the bipolar disorder? PMID- 26883245 TI - The atomistic origin of interface confinement and enhanced conversion efficiency in Si nanowire solar cells. AB - The photoelectric properties of Si nanowires (SiNWs) under interface confinement are investigated based on the atomic-bond-relaxation consideration and the detailed balance principle. An analytical model is developed to elucidate the interface confinement and power conversion efficiency (PCE). It is found that the band curvature and surface barrier height decrease with decreasing size. The interface recombination rate and PCE can be determined by the size, shell thickness and local interface conditions. Our theoretical results show evident improvement in the PCE of SiNWs under interface confinement compared to that of a bare nanowire, highlighting the feasibility of the epitaxial layer as a booster for highly efficient SiNW solar cells. PMID- 26883246 TI - Ethnopharmacological survey about medicinal plants utilized by herbalists and traditional practitioner healers for treatments of diarrhea in the West Bank/Palestine. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Folk herbal medicine knowledge and its utilization by aboriginal cultures are not only useful for conservation of cultural traditions and biodiversity, but also useful for community healthcare and drug discovery in the present and in the future. AIM OF THE STUDY: Using a semi-structured questionnaire, an ethnopharmacological survey of medicinal plants used for treatment of diarrhea in the West Bank/Palestine was investigated. RESULTS: Information about fifty medicinal plants used for treatment of diarrhea, including the names of plants, parts used, mode and methods of preparation was obtained from 100 traditional healers and herbalists. This research is the first scientific work in the Middle East to collect data about plants used by traditional healers for treatments of diarrhea and their evidence based effects against this disease. The fidelity levels were 97% for Salvia fruticosa, Teucrium polium and Musa paradisiaca, 95% for Camellia sinensis and Aegle marmelos, 79% for Oryza sativa and Solanum tuberosum, 77% for Quercus boissieri, 66% for Psidium guajava, 56% for Anthemis palestina, 54% for Solanum nigrum and 52% for Juglans regia while the highest use and choice values were for S. fruticosa, T. polium and M. paradisiaca as well as the factor of informant's consensus for medicinal plants used for treatment of diarrhea was 0.505.The leaves were the most commonly used parts, followed by fruits, roots and rhizomes, while decoctions and infusions are the preferred methods of preparation. CONCLUSIONS: The Palestinian traditional medicine is rich with herbal remedies for treatment of diarrhea in comparison with other countries, but most of these herbal remedies lack standard in-vitro and in-vivo evaluations to establish their antidiarrheal effects. Therefore, the information obtained can serve as a basis for further phytochemical and pharmacological studies to determine their efficacy and safety which might contribute to a better integration of Palestinian traditional medicine into the national health system in the future. PMID- 26883247 TI - Risk to fragmented DNA in dry, wet, and frozen states from computed tomography: a comparative theoretical study. AB - Computed tomography represents the gold standard in forensic and palaeopathological diagnosis. However, the X-rays used may affect the DNA quality through fragmentation and loss of genetic information. Previous work showed that the effects of ionizing radiation on dry DNA are non-significant with P < 10(-8), which cannot be detected by means of polymerase chain reaction methods. In the present paper, complete analytical model that characterizes radiation effects on fragmented DNA in dry, wet, and frozen states is described. Simulation of radiation tracks in water phantom cells was performed using the Geant4-DNA toolkit. Cell hits by electrons with energies between 5 and 20 keV were simulated, and the formation of radiolytic products was assessed at a temperature of 298 K. The diffusion coefficient and the mean square displacement of reactive species were calculated by Stokes-Einstein-Smoluchowski relations at 273 K. Finally, DNA fragment damage was estimated using the density distribution of fragments calculated from atomic force microscopy images. The lowest probability of radiation-induced DNA damage was observed for dry state, with a range from 2.5 * 10(-9) to 7.8 * 10(-12) at 298 K, followed by that for frozen state, with a range from 0.9 to 4 * 10(-7) at 273 K. The highest probability of radiation induced DNA damage was demonstrated for fragmented DNA in wet state with a range from 2 to 9 * 10(-7) at 298 K. These results significantly improve the interpretation of CT imaging in future studies in forensic and palaeopathological science. PMID- 26883248 TI - Identifying Mechanisms Behind the Tullio Phenomenon: a Computational Study Based on First Principles. AB - Patients with superior canal dehiscence (SCD) suffer from events of dizziness and vertigo in response to sound, also known as Tullio phenomenon (TP). The present work seeks to explain the fluid-dynamical mechanisms behind TP. In accordance with the so-called third window theory, we developed a computational model for the vestibular signal pathway between stapes and SCD. It is based on first principles and accounts for fluid-structure interactions arising between endolymph, perilymph, and membranous labyrinth. The simulation results reveal a wave propagation phenomenon in the membranous canal, leading to two flow phenomena within the endolymph which are in close interaction. First, the periodic deformation of the membranous labyrinth causes oscillating endolymph flow which forces the cupula to oscillate in phase with the sound stimulus. Second, these primary oscillations of the endolymph induce a steady flow component by a phenomenon known as steady streaming. We find that this steady flow of the endolymph is typically in ampullofugal direction. This flow leads to a quasi-steady deflection of the cupula which increases until the driving forces of the steady streaming are balanced by the elastic reaction forces of the cupula, such that the cupula attains a constant deflection amplitude which lasts as long as the sound stimulus. Both response types have been observed in the literature. In a sensitivity study, we obtain an analytical fit which very well matches our simulation results in a relevant parameter range. Finally, we correlate the corresponding eye response (vestibulo-ocular reflex) with the fluid dynamics by a simplified model of lumped system constants. The results reveal a "sweet spot" for TP within the audible sound spectrum. We find that the underlying mechanisms which lead to TP originate primarily from Reynolds stresses in the fluid, which are weaker at lower sound frequencies. PMID- 26883249 TI - Carotid artery stenting versus carotid endarterectomy: updated meta-analysis, metaregression and trial sequential analysis of short-term and intermediate-to long-term outcomes of randomized trials. AB - INTRODUCTION: To compare carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in the treatment of carotid stenosis, including two recently published, prospective, randomized trials of these therapies. EVIDENCE ACQUISITION: A multiple electronic health database search on all randomized trials describing CAS compared with CEA in patients with symptomatic or asymptomatic carotid artery stenosis was performed. Primary outcomes were death, stroke, and myocardial infarction. EVIDENCE SYNTHESIS: Carotid artery stenting as compared with CEA was associated with a 61% increase in the risk of periprocedural death or stroke (Peto OR, 1.609; 95% confidence interval [CI]: 1.193-2.170; P=0.002). The trial sequential monitoring boundary was crossed by the cumulative Z-curve, suggesting firm evidence for at least a 20% relative risk increase of periprocedural death or stroke and any stroke compared with CEA. Carotid artery stenting as compared with CEA was associated with a 42% increase in the risk for the composite of periprocedural stroke or death plus ipsilateral stroke thereafter (Peto OR, 1.417; 95% CI: 1.074-1.870; P=0.0014). CONCLUSIONS: In this largest and most comprehensive meta-analysis to date using outcomes that are standard in contemporary studies, CAS was associated with an increased risk of both periprocedural and intermediate- to long-term outcomes. PMID- 26883250 TI - Long noncoding RNA ENST00000434223 suppressed tumor progression in non-small cell lung cancer. AB - In spite of the fact that the great progress has been made in the treatment of non-small cell lung cancer (NSCLC), the prognosis of NSCLC remains comparatively dismal. Therefore, it is of great value to identify novel effective diagnostic biomarkers and therapeutic targets of NSCLC. Emerging evidence has demonstrated the vital roles of long noncoding RNAs (lncRNAs) in cancer development. ENST00000434223 was recently identified as a lncRNA that is downregulated in early stage lung adenocarcinoma in a profiling study. However, little is known about its role in the development of NSCLC. In the present study, we found that ENST00000434223 was greatly downregulated in cancer tissues compared to adjacent normal tissues. ENST00000434223 overexpression suppressed the proliferation and migration in NSCLC cell lines in vitro. Moreover, ENST00000434223 overexpression reversed the epithelial-mesenchymal transition in NSCLC cell line. Our study suggests that ENST00000434223 may be a potential biomarker and a therapeutic target of NSCLC. PMID- 26883251 TI - Linc-ROR induces epithelial-mesenchymal transition and contributes to drug resistance and invasion of breast cancer cells. AB - We aimed to investigate the role of large intergenic noncoding RNA regulator of reprogramming (linc-ROR) in the chemotherapy resistance of human breast cancer (BC) cells and its mechanism. A total of 142 patients diagnosed with BC in the First Affiliated Hospital, Zhejiang University between January 2012 and January 2014 were enrolled in our study. The BC tissues and the adjacent normal tissues (5 cm away from tumor tissue) of the enrolled patients were selected, and human BC cell lines (MCF10A, SK-BR-3, MCF-7, Bcap-37, MDA-MB-231, and T47D) were also selected. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) 2H-tetrazolium, inner salt (MTS) assay, and Transwell were applied in our study. Expression level of linc-ROR messenger RNA (mRNA) in BC tissues was clearly higher than that in adjacent normal tissues, and significant difference was found between expression level of linc-ROR mRNA and lymph node metastasis (all P < 0.05). Linc-ROR was highly expressed in others BC cell lines compared with that in immortalized mammary epithelial cells (MECs) MCF10A (both P < 0.05), while MDA MB231 cell presented the higher expression (P < 0.001). Under different concentrations of 5-FU and paclitaxel in MDA-MB231 cell, E-cadherin mRNA and protein expressions increased gradually with the increase of concentrations, and Vimentin and N-cadherin mRNA and protein expressions decreased gradually with the decrease of concentrations (all P < 0.05). Compared with shCtrl group, MDA-MB231 cell in shROR group presented higher sensibility of 5-FU and paclitaxel with increased E-cadherin expression, decreased Vimentin and N-cadherin expression and invasion ability (all P < 0.05). Compared with vector cell, overexpressed linc ROR cell presented decreased sensibility of 5-FU and paclitaxel with decreased E cadherin expression, increased Vimentin, N-cadherin expression, and invasion ability (all P < 0.05). Our study demonstrated that linc-ROR is an important marker for multidrug resistance of BC, and its up-regulation is important for chemotherapy tolerance and invasion of BC. PMID- 26883252 TI - Long noncoding RNA SPRY4-IT1 promotes esophageal squamous cell carcinoma cell proliferation, invasion, and epithelial-mesenchymal transition. AB - The biology of esophageal squamous cell carcinoma (ESCC) remains poorly understood. Long noncoding RNAs (lncRNAs) are found to be dysregulated in a variety of cancers, including ESCC. SPRY4-IT1 has been recently revealed as oncogenic regulator or tumor suppressors in different cancers; however, whether SPRY4-IT1 is involved in ESCC remains poorly understood. To investigate the role of SPRY4-IT1 in ESCC, we evaluated the SPRY4-IT1 expression levels in a series of ESCC patients and a panel of ESCC cell line using qRT-PCR. CCK8 and colony formation assay were performed to assess the effect of SPRY4-IT1siRNA on cell proliferation, migration, and invasion of ESCC cell lines. SPRY4-IT1 expression was upregulated in ESCC tissues and the higher expression of SPRY4-IT1 was significantly correlated with tumor grade, depth of invasion, and lymph node metastasis. Moreover, silencing of SPRY4-IT1 expression inhibited ESCC cell proliferation, colony formation, migration, and invasion. Therefore, our study indicates that SPRY4-IT1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC. PMID- 26883253 TI - Telomere length in peripheral leukocytes is associated with immune cell tumor infiltration and prognosis in colorectal cancer patients. AB - Telomeres are protective structures at the end of chromosomes, essential for chromosomal integrity. A large number of studies have investigated leukocyte telomere length as a possible risk marker for various cancers, colorectal cancer (CRC) included. In contrast, studies investigating leukocyte telomere length in relation to CRC survival are lacking. We previously reported that relative telomere length (RTL) of leukocytes collected at diagnosis predicted survival in patients with breast and kidney cancer. We suggested that these findings might reflect various immunological mechanisms, affected by the presence of a tumor. In the present study, leukocyte RTL was examined in relation to immune cell tumor infiltration and prognosis in 130 patients with CRC diagnosis. RTL was measured with a well-established qPCR method. We found that patients with the highest degree of lymphocyte tumor infiltration had shorter leukocyte RTL. Consistent with our previous findings, short RTL was a favorable prognostic marker in univariate survival analysis. In the current study, RTL did not remain as an independent predictor in multivariate survival analysis, when including metastatic status in the model. However, a non-significant trend towards a similar telomere-associated survival pattern was observed in patients with limited disease. In contrast, for patients who died of other causes than CRC, short RTL was associated with significantly shorter survival time. To our knowledge, this is the first study to investigate an association between leukocyte RTL, immune cell tumor infiltration, and cancer-specific survival in CRC patients. Larger studies are warranted to verify these findings. PMID- 26883254 TI - Decreased expression of Siglec-8 associates with poor prognosis in patients with gastric cancer after surgical resection. AB - The expression of sialic acid-binding Ig-like lectin (Siglec) family has been detected in many malignant tumors and correlated with patient outcomes. The present study aims to investigate the prognostic value of Siglec-8 expression and refine current risk stratification system in patients with gastric cancer. Two independent sets of patients (n = 78; n = 356, respectively) with gastric cancer from Zhongshan Hospital were enrolled into this study. The expression of Siglec-8 was detected by immunohistochemistry. Cox regression analysis was used to assess the prognostic value of Siglec-8 expression and clinical outcomes. A novel molecular prognostic stratification system combining intratumoral Siglec-8 expression with TNM stage was determined by means of receiver operating characteristic analysis. Multivariate Cox regression analysis identified that intratumoral Siglec-8 low expression was an independent prognostic factor for dismal overall survival of patients with gastric cancer. Incorporating intratumoral Siglec-8 expression into the current TNM staging system showed more accuracy for predicting prognosis of patients with gastric cancer. Our study suggested that intratumoral Siglec-8 expression was an independent prognostic factor for overall survival of patients with gastric cancer. Incorporating Siglec 8 expression level into current TNM staging system might add more comprehensive prognostic information for patients with gastric cancer and lead to a more precise risk stratification system for predicting clinical outcomes. PMID- 26883255 TI - Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: we are not sure. PMID- 26883256 TI - Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: no. PMID- 26883257 TI - Steroids are part of rescue therapy in ARDS patients with refractory hypoxemia: yes. PMID- 26883258 TI - Efficiency and safety of apnea test process under extracorporeal membrane oxygenation: the most effective method remains questionable. PMID- 26883259 TI - Twin Screw Extruders as Continuous Mixers for Thermal Processing: a Technical and Historical Perspective. AB - Developed approximately 100 years ago for natural rubber/plastics applications, processes via twin screw extrusion (TSE) now generate some of the most cutting edge drug delivery systems available. After 25 or so years of usage in pharmaceutical environments, it has become evident why TSE processing offers significant advantages as compared to other manufacturing techniques. The well characterized nature of the TSE process lends itself to ease of scale-up and process optimization while also affording the benefits of continuous manufacturing. Interestingly, the evolution of twin screw extrusion for pharmaceutical products has followed a similar path as previously trodden by plastics processing pioneers. Almost every plastic has been processed at some stage in the manufacturing train on a twin screw extruder, which is utilized to mix materials together to impart desired properties into a final part. The evolution of processing via TSEs since the early/mid 1900s is recounted for plastics and also for pharmaceuticals from the late 1980s until today. The similarities are apparent. The basic theory and development of continuous mixing via corotating and counterrotating TSEs for plastics and drug is also described. The similarities between plastics and pharmaceutical applications are striking. The superior mixing characteristics inherent with a TSE have allowed this device to dominate other continuous mixers and spurred intensive development efforts and experimentation that spawned highly engineered formulations for the commodity and high-tech plastic products we use every day. Today, twin screw extrusion is a battle hardened, well-proven, manufacturing process that has been validated in 24 h/day industrial settings. The same thing is happening today with new extrusion technologies being applied to advanced drug delivery systems to facilitate commodity, targeted, and alternative delivery systems. It seems that the "extrusion evolution" will continue for wide-ranging pharmaceutical products. PMID- 26883260 TI - Characterization and In Vitro Evaluation of the Complexes of Posaconazole with beta- and 2,6-di-O-methyl-beta-cyclodextrin. AB - Posaconazole is a triazole antifungal drug that with extremely poor aqueous solubility. Up to now, this drug can be administered via intravenous injection and oral suspension. However, its oral bioavailability is greatly limited by the dissolution rate of the drug. This study aimed to improve water solubility and dissolution of posaconazole through characterizing the inclusion complexes of posaconazole with beta-cyclodextrin (beta-CD) and 2,6-di-O-methyl-beta cyclodextrin (DM-beta-CD). Phase solubility studies were performed to calculate the stability constants in solution. The results of FT-IR, PXRD, 1H and ROESY 2D NMR, and DSC all verified the formation of the complexes in solid state. The complexes showed remarkably improved water solubility and dissolution rate than pure posaconazole. Especially, the aqueous solubility of the DM-beta-CD complex is nine times higher than that of the beta-CD complex. Preliminary in vitro antifungal susceptibility tests showed that the two inclusion complexes maintained high antifungal activities. These results indicated that the DM-beta CD complexes have great potential for application in the delivery of poorly water soluble antifungal agents, such as posaconazole. PMID- 26883261 TI - Structural and Surface Compatibility Study of Modified Electrospun Poly(epsilon caprolactone) (PCL) Composites for Skin Tissue Engineering. AB - In this study, biodegradable poly(epsilon-caprolactone) (PCL) nanofibers (PCL NF), collagen-coated PCL nanofibers (Col-c-PCL), and titanium dioxide incorporated PCL (TiO2-i-PCL) nanofibers were prepared by electrospinning technique to study the surface and structural compatibility of these scaffolds for skin tisuue engineering. Collagen coating over the PCL nanofibers was done by electrospinning process. Morphology of PCL nanofibers in electrospinning was investigated at different voltages and at different concentrations of PCL. The morphology, interaction between different materials, surface property, and presence of TiO2 were studied by scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), contact angle measurement, energy dispersion X ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). MTT assay and cell adhesion study were done to check biocompatibilty of these scaffolds. SEM study confirmed the formation of nanofibers without beads. FTIR proved presence of collagen on PCL scaffold, and contact angle study showed increment of hydrophilicity of Col-c-PCL and TiO2-i-PCL due to collagen coating and incorporation of TiO2, respectively. EDX and XPS studies revealed distribution of entrapped TiO2 at molecular level. MTT assay and cell adhesion study using L929 fibroblast cell line proved viability of cells with attachment of fibroblasts over the scaffold. Thus, in a nutshell, we can conclude from the outcomes of our investigational works that such composite can be considered as a tissue engineered construct for skin wound healing. PMID- 26883262 TI - Design and In Vitro/In Vivo Evaluation of Ultra-Thin Mucoadhesive Buccal Film Containing Fluticasone Propionate. AB - Fluticasone propionate is a synthetic corticosteroid drug distinguished by its potent anti-inflammatory action with low systemic side effects in comparison to other corticosteroids making it a potential drug for local buccal delivery. The aim of the present study was to design mucoadhesive buccal film containing fluticasone that is aesthetically acceptable and could maintain local drug release for a sustained period to manage the sign and symptoms of severe erosive mouth lesions. Solvent casting technique was used in film preparation. Different polymeric blends were used either alone or in combination with mucoadhesive polymers, sodium carboxymethyl cellulose (SCMC), or Carbopol 971P at different concentrations. The physicochemical properties, in vitro mucoadhesion time as well as the drug release properties for all prepared formulations were determined. Selected formulations with adequate properties were further examined by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) and subjected to in vivo evaluation. Films containing hydroxypropyl methylcellulose (HPMC)/ethyl cellulose (EC) showed acceptable physicochemical properties, homogenous drug distribution, convenient mucoadhesion time, moderate swelling as well as sustained drug release up to 12 h. The biological performance of these formulations was assessed on healthy human volunteers and compared with a prepared mouthwash which showed enhanced pharmacokinetic parameters for the selected films in comparison to the mouthwash. The results revealed that the optimized formulation containing HPMC/EC and 10% SCMC could successfully achieve sustained drug release for 10 h which is considered promising for local treatment of severe mouth lesions. PMID- 26883263 TI - Design and Evaluation of Hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-Order Controlled Delivery of Water-Insoluble Drugs. AB - The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f 2. Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel-Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error. PMID- 26883264 TI - Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency. AB - We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins. PMID- 26883265 TI - The effect of total hip arthroplasty on sagittal spinal-pelvic-leg alignment and low back pain in patients with severe hip osteoarthritis. AB - PURPOSE: Sagittal spinopelvic malalignment has been reported in spinal disorders such as low back pain (LBP), and restoration of normal alignment is targeted when treating these disorders. Abnormal sagittal spinal-pelvic-leg alignment has been reported in patients with severe hip osteoarthritis (OA), who have a high prevalence of associated LBP. This prospective longitudinal study aimed to investigate changes in sagittal spinal-pelvic-leg alignment after total hip arthroplasty (THA) in patients with severe hip OA, and whether these changes contribute to LBP relief. METHODS: Patients undergoing primary THA due to severe unilateral hip OA were recruited. Physical examination and X-ray films were taken to rule out any spinal disorder. Sagittal alignment of pelvis, hip, and spine was analyzed on lateral radiographs taken before (baseline) and 1 year after (follow up) THA. Functional instruments were completed by patients including: visual analog scale (VAS) for LBP, Roland-Morris Disability Questionnaire (RMDQ), and Harris Hip Score (HHS). Comparisons were carried out at baseline and follow-up, and between patients with and without LBP. RESULTS: The recruited 69 patients showed significantly reduced hip flexion and improved global spinal balance at follow-up compared with baseline. LBP was reported by 39 patients (56.5 %) before surgery; at follow-up, 17 reported complete resolution, while 22 reported significant relief. Significant decreases in VAS and RMDQ scores in lumbar spine and increase in hip HHS were observed. CONCLUSIONS: THA in patients with severe hip OA could help correct abnormal sagittal spinal-pelvic-leg alignment and relieve comorbid LBP. Improvements in hip flexion and global spinal balance might be involved in the mechanism of LBP relief. PMID- 26883266 TI - Overcorrection of lumbar lordosis for adult spinal deformity with sagittal imbalance: comparison of radiographic outcomes between overcorrection and undercorrection. AB - PURPOSE: To determine the correlation of the difference between postoperative lumbar lordosis (LL) and ideal LL with the sagittal vertical axis (SVA) at the final follow-up in patients with adult spinal deformity (ASD). METHODS: Fifty-one patients with degenerative lumbar kyphosis (DLK) (mean age 66.5 years) who underwent surgical correction with a minimum 2-year follow-up were evaluated. Based on the difference between postoperative LL and ideal LL using the Korean version of Legaye's formula, we divided the 51 patients into two groups: overcorrection (degree of postoperative LL > ideal LL) and undercorrection (degree of postoperative LL < ideal LL). RESULTS: Our clinical series of patients comprised 24 in the overcorrection and 27 in the undercorrection group. No significant differences were found in preoperative pelvic incidence (PI 52.6 degrees vs. 57.3 degrees ), sacral slope (SS 23.3 degrees vs. 18.3 degrees ), LL (-6.9 degrees vs. -2.3 degrees ), thoracic kyphosis (TK 4.7 degrees vs. 4.9 degrees ) and SVA (140 vs. 139 mm) except pelvic tilt (PT 29.4 degrees vs. 39.0 degrees ), between the two groups. All the patients in the overcorrection group and 16 in the undercorrection group achieved postoperative optimal sagittal balance based on SVA <= 50 mm. In addition, significant differences in PT (10.5 degrees vs. 26.7 degrees ), SS (42.1 degrees vs. 30.6 degrees ), LL (-64.3 degrees vs. -37.1 degrees ), TK (22.6 degrees vs. 15.8 degrees ), and SVA (-1 vs. 41 mm) between the two groups were observed postoperatively. Furthermore, four patients (16.7 %) in the overcorrection group and eight (50 %) in the undercorrection group had sagittal decompensation at the final follow-up. Our results showed that the difference between postoperative LL and ideal LL had a significant correlation with postoperative and final follow-up SVA in our clinical series. CONCLUSION: Overcorrection of LL is an effective treatment modality to maintain optimal sagittal alignment in patients with DLK; this suggests that it should be considered in preoperative planning for patients with ASD with sagittal imbalance. PMID- 26883267 TI - Collaboration to Understand Complex Diseases: Preeclampsia and Adverse Pregnancy Outcomes. PMID- 26883268 TI - Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1alpha Knockout and Wild-Type Mice. AB - We recently showed that alpha, beta, and gamma splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1beta accounts for most of the NO generation. We have also demonstrated that the mice with deletion of NOS1 specifically from the macula densa developed salt-sensitive hypertension. However, the global NOS1 knockout (NOS1KO) strain is neither hypertensive nor salt sensitive. This global NOS1KO strain is actually an NOS1alphaKO model. Consequently, we hypothesized that inhibition of NOS1beta in NOS1alphaKO mice induces salt-sensitive hypertension. NOS1alphaKO and C57BL/6 wild-type (WT) mice were implanted with telemetry transmitters and divided into 7-nitroindazole (10 mg/kg/d)-treated and nontreated groups. All of the mice were fed a normal salt (0.4% NaCl) diet for 5 days, followed by a high-salt diet (4% NaCl). NO generation by the macula densa was inhibited by >90% in WT and NOS1alphaKO mice treated with 7-nitroindazole. Glomerular filtration rate in conscious mice was increased by ~ 40% after a high-salt diet in both NOS1alphaKO and WT mice. In response to acute volume expansion, glomerular filtration rate, diuretic and natriuretic response were significantly blunted in the WT and knockout mice treated with 7-nitroindazole. Mean arterial pressure had no significant changes in mice fed a high-salt diet, but increased ~ 15 mm Hg similarly in NOS1alphaKO and WT mice treated with 7-nitroindazole. We conclude that NOS1beta, but not NOS1alpha, plays an important role in control of sodium excretion and hemodynamics in response to either an acute or a chronic salt loading. PMID- 26883269 TI - Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation. AB - This study aims to understand the special expression patterns of angiotensin-II receptor (AT1R and AT2R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT1R and AT2R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17beta-estradiol on blood pressure and AT2R expression were also tested. The data showed that AT2R, rather than AT1R, expression was higher in female than age-matched male rats. Moreover, AT2R was downregulated in ovariectomized rats, which was restored by the administration of 17beta estradiol. Single-cell real time-polymerase chain reaction data indicated that AT2R was uniquely expressed in Ah-type BRNs. Functional study showed that long term administration of 17beta-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah- than C type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed by iberiotoxin. The density of angiotensin-II-sensitive K(+) currents recorded in Ah-types was equivalent with iberiotoxin-sensitive component. In summary, the unique, sex- and afferent-specific expression of AT2R was identified in Ah-type BRNs, and AT2R-mediated KCa1.1 inhibition in Ah-type BRNs may exert great impacts on baroreflex afferent function and blood pressure regulation in females. PMID- 26883270 TI - New Quality Measure Core Sets Provide Continuity for Measuring Quality Improvement: Concerns Raised About Conflicting Blood Pressure Measures. PMID- 26883271 TI - ABCG2 and ABCB1 Limit the Efficacy of Dasatinib in a PDGF-B-Driven Brainstem Glioma Model. AB - Dasatinib is a multikinase inhibitor in clinical trials for glioma, and thus far has failed to demonstrate significant efficacy. We investigated whether the ABC efflux transporters ABCG2 and ABCB1 expressed in the blood-brain barrier (BBB), are limiting the efficacy of dasatinib in the treatment of glioma using genetic and pharmacologic approaches. We utilized a genetic brainstem glioma mouse model driven by platelet-derived growth factor-B and p53 loss using abcg2/abcb1 wild type (ABC WT) or abcg2/abcb1 knockout mice (ABC KO). First, we observed that brainstem glioma tumor latency is significantly prolonged in ABC KO versus ABC WT mice (median survival of 47 vs. 34 days). Dasatinib treatment nearly doubles the survival of brainstem glioma-bearing ABC KO mice (44 vs. 80 days). Elacridar, an ABCG2 and ABCB1 inhibitor, significantly increases the efficacy of dasatinib in brainstem glioma-bearing ABC WT mice (42 vs. 59 days). Pharmacokinetic analysis demonstrates that dasatinib delivery into the normal brain, but not into the tumor core, is significantly increased in ABC KO mice compared with ABC WT mice. Surprisingly, elacridar did not significantly increase dasatinib delivery into the normal brain or the tumor core of ABC WT mice. Next, we demonstrate that the tight junctions of the BBB of this model are compromised as assessed by tissue permeability to Texas Red dextran. Finally, elacridar increases the cytotoxicity of dasatinib independent of ABCG2 and ABCB1 expression in vitro In conclusion, elacridar improves the efficacy of dasatinib in a brainstem glioma model without significantly increasing its delivery to the tumor core. Mol Cancer Ther; 15(5); 819-29. (c)2016 AACR. PMID- 26883272 TI - Targeting Adenine Nucleotide Translocase-2 (ANT2) to Overcome Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer. AB - EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy has achieved favorable clinical outcomes in non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, patients eventually develop resistance to EGFR-TKIs by several mechanisms. Adenine nucleotide translocase-2 (ANT2) is an oncogenic mitochondrial membrane-associated protein. We investigated the therapeutic potential of ANT2 inhibition to EGFR-TKI resistance in NSCLC using gefitinib-sensitive (PC9 and HCC827) and gefitinib-resistant (H1975 and HCC827/GR) NSCLC cell lines. ANT2 was inhibited by transfecting cells with an ANT2-specific shRNA. ANT2 expression was elevated in the H1975 and HCC827/GR cells compared with the PC9 and HCC827 cells. ANT2 upregulation in gefitinib-resistant cells was associated with increased SP1 binding to the ANT2 promoter. ANT2-specific shRNA decreased NSCLC cell viability. Moreover, ANT2-specific shRNA sensitized the H1975 and HCC827/GR cells to gefitinib, accompanied by HSP90 and EGFR downregulation. ANT2-specific shRNA also inactivated the PI3K/Akt signaling pathway in the H1975 and HCC827/GR cells, which was mediated by the suppression of miR-221/222 levels and by the subsequent restoration of PTEN. In EGFR-TKI-treated NSCLC patients, ANT2 expression was higher in patients exhibiting poor responses compared with patients showing excellent responses. Furthermore, ANT2 expression increased in tumor tissues biopsied after acquiring gefitinib resistance compared with tissues before gefitinib treatment. These findings suggest that ANT2 overexpression contributes to EGFR-TKI resistance in NSCLC and that ANT2 targeting may be considered a novel strategy for overcoming this resistance. Mol Cancer Ther; 15(6); 1387-96. (c)2016 AACR. PMID- 26883273 TI - Identification of a Small Molecule That Overcomes HdmX-Mediated Suppression of p53. AB - Inactivation of the p53 tumor suppressor by mutation or overexpression of negative regulators occurs frequently in cancer. As p53 plays a key role in regulating proliferation or apoptosis in response to DNA-damaging chemotherapies, strategies aimed at reactivating p53 are increasingly being sought. Strategies to reactivate wild-type p53 include the use of small molecules capable of releasing wild-type p53 from key, cellular negative regulators, such as Hdm2 and HdmX. Derivatives of the Hdm2 antagonist Nutlin-3 are in clinical trials. However, Nutlin-3 specifically disrupts Hdm2-p53, leaving tumors harboring high levels of HdmX resistant to Nutlin-3 treatment. Here, we identify CTX1, a novel small molecule that overcomes HdmX-mediated p53 repression. CTX1 binds directly to HdmX to prevent p53-HdmX complex formation, resulting in the rapid induction of p53 in a DNA damage-independent manner. Treatment of a panel of cancer cells with CTX1 induced apoptosis or suppressed proliferation and, importantly, CTX1 demonstrates promising activity as a single agent in a mouse model of circulating primary human leukemia. CTX1 is a small molecule HdmX inhibitor that demonstrates promise as a cancer therapeutic candidate. Mol Cancer Ther; 15(4); 574-82. (c)2016 AACR. PMID- 26883274 TI - MR Studies of Glioblastoma Models Treated with Dual PI3K/mTOR Inhibitor and Temozolomide:Metabolic Changes Are Associated with Enhanced Survival. AB - The current standard of care for glioblastoma (GBM) is surgical resection, radiotherapy, and treatment with temozolomide (TMZ). However, resistance to current therapies and recurrence are common. To improve survival, agents that target the PI3K signaling pathway, which is activated in approximately 88% of GBM, are currently in clinical trials. A challenge with such therapies is that tumor shrinkage is not always observed. New imaging methods are therefore needed to monitor response to therapy and predict survival. The goal of this study was to determine whether hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) and (1)H magnetic resonance spectroscopy (MRS) can be used to monitor response to the second-generation dual PI3K/mTOR inhibitor voxtalisib (XL765, SAR245409), alone or in combination with TMZ. We investigated GS-2 and U87-MG GBM orthotopic tumors in mice, and used MRI, hyperpolarized (13)C MRSI, and (1)H MRS to monitor the effects of treatment. In our study, (1)H MRS could not predict tumor response to therapy. However, in both our models, we observed a significantly lower hyperpolarized lactate-to-pyruvate ratio in animals treated with voxtalisib, TMZ, or combination therapy, when compared with controls. This metabolic alteration was observed prior to MRI-detectable changes in tumor size, was consistent with drug action, and was associated with enhanced animal survival. Our findings confirm the potential translational value of the hyperpolarized lactate-to-pyruvate ratio as a biomarker for noninvasively assessing the effects of emerging therapies for patients with GBM. Mol Cancer Ther; 15(5); 1113-22. (c)2016 AACR. PMID- 26883275 TI - The predictive performance of the SAPS II and SAPS 3 scoring systems: A retrospective analysis. AB - PURPOSE: The purpose was to analyze and compare the performance of Simplified Acute Physiology Score (SAPS) II and SAPS 3 (North Europe Logit) in an intensive care unit (ICU) for internal disorders at a German university hospital. MATERIALS AND METHODS: This retrospective study was conducted at a single-center 12-bed ICU sector for Internal Medicine in Essen, Germany, within an 18-month period. Data for adult ICU patients (N = 548) were evaluated. SAPS II and SAPS 3 scores were assessed along with the predicted mortality rates. Discrimination was evaluated by calculating the area under the receiver operating characteristic curve, and calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit C-test. The ratios of observed-to-expected deaths (standardized mortality ratio, SMR) were calculated along with the 95% confidence intervals (95% CIs). RESULTS: The in hospital mortality rate was 22.6%, which provided an SMR of 0.91 (95% CI, 0.77 0.99) for SAPS II and 0.62 (95% CI, 0.52-0.71) for SAPS 3. Both SAPS II and SAPS 3 exhibited acceptable discrimination, with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.79-0.89) and 0.73 (95% CI, 0.67-0.79), respectively. However, SAPS II demonstrated superior SMR-based discrimination, which was closer to the observed mortality rate, compared with SAPS 3. Calibration curves exhibited similar performance based on the Hosmer-Lemeshow goodness-of-fit C-test results: chi(2) = 7.10 with P = .525 for SAPS II and chi(2) = 3.10 with P = .876 for SAPS 3. Interestingly, both scores overpredicted mortality. CONCLUSIONS: In this study, SAPS 3 overestimated mortality and therefore appears less suitable for risk evaluation in comparison to SAPS II. PMID- 26883276 TI - Growth factors, aging and age-related diseases. AB - Simple organisms including yeast and flies with mutations in the IGF-1 and Tor S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID- 26883278 TI - Deciphering the origin of giant magnetic anisotropy and fast quantum tunnelling in Rhenium(IV) single-molecule magnets. AB - Single-molecule magnets represent a promising route to achieve potential applications such as high-density information storage and spintronics devices. Among others, 4d/5d elements such as Re(IV) ion are found to exhibit very large magnetic anisotropy, and inclusion of this ion-aggregated clusters yields several attractive molecular magnets. Here, using ab intio calculations, we unravel the source of giant magnetic anisotropy associated with the Re(IV) ions by studying a series of mononuclear Re(IV) six coordinate complexes. The low-lying doublet states are found to be responsible for large magnetic anisotropy and the sign of the axial zero-field splitting parameter (D) can be categorically predicted based on the position of the ligand coordination. Large transverse anisotropy along with large hyperfine interactions opens up multiple relaxation channels leading to a fast quantum tunnelling of the magnetization (QTM) process. Enhancing the Re ligand covalency is found to significantly quench the QTM process. PMID- 26883277 TI - Effects of High Hydrostatic Pressure on Expression Profiles of In Vitro Produced Vitrified Bovine Blastocysts. AB - High hydrostatic pressure (HHP) has been used to pre-condition embryos before essential, yet potentially detrimental procedures such as cryopreservation. However, the mechanisms for HHP are poorly understood. We treated bovine blastocysts with three different HHP (40, 60 and 80 MPa) in combination with three recovery periods (0, 1 h, 2 h post HHP). Re-expansion rates were significantly higher at 40 and 60 but lower at 80 MPa after vitrification-warming in the treated groups than controls. Microarray analysis revealed 399 differentially expressed transcripts, representing 254 unique genes, among different groups. Gene ontology analysis indicated that HHP at 40 and 60 MPa promoted embryo competence through down-regulation of genes in cell death and apoptosis, and up-regulation of genes in RNA processing, cellular growth and proliferation. In contrast, 80 MPa up-regulated genes in apoptosis, and down regulated protein folding and cell cycle-related genes. Moreover, gene expression was also influenced by the length of the recovery time after HHP. The significantly over-represented categories were apoptosis and cell death in the 1 h group, and protein folding, response to unfolded protein and cell cycle in the 2 h group compared to 0 h. Taken together, HHP promotes competence of vitrified bovine blastocysts through modest transcriptional changes. PMID- 26883279 TI - Accurate and molecular-size-tolerant NMR quantitation of diverse components in solution. AB - Determining the amount of each component of interest in a mixture is a fundamental first step in characterizing the nature of the solution and to develop possible means of utilization of its components. Similarly, determining the composition of units in complex polymers, or polymer mixtures, is crucial. Although NMR is recognized as one of the most powerful methods to achieve this and is widely used in many fields, variation in the molecular sizes or the relative mobilities of components skews quantitation due to the size-dependent decay of magnetization. Here, a method to accurately determine the amount of each component by NMR was developed. This method was validated using a solution that contains biomass-related components in which the molecular sizes greatly differ. The method is also tolerant of other factors that skew quantitation such as variation in the one-bond C-H coupling constant. The developed method is the first and only way to reliably overcome the skewed quantitation caused by several different factors to provide basic information on the correct amount of each component in a solution. PMID- 26883280 TI - Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease of unknown etiology. It is characterized by the presence of rheumatoid factor and anti-citrullinated peptide antibodies. Initial phase of RA involves the activation of both T and B cells. Cytokines have a crucial role in the pathophysiology of RA as pro-inflammatory cytokines such as TNFalpha, IL-1, IL-17 stimulates inflammation and degradation of bone and cartilage. There occurs an imbalance between the pro- and anti-inflammatory cytokine activities which leads to multisystem immune complications. There occurs a decline in the number of Treg cells which may also play an important role in pathophysiology of the disease. In RA patients, serum or plasma level of cytokines may indicate the severity of disease. Cytokine gene polymorphism could be used as markers of susceptibility and severity of RA. Anti-cytokine agents seem to emerge as potent drug molecules to treat RA. Many clinical trials are ongoing and several positive results have been obtained. There is a need to develop potential anti-cytokine agents that target numerous pathways involved in the pathogenesis of RA. This review article describes the effector functions of pro- and anti-inflammatory cytokines and the role of cytokine gene polymorphism in the pathogenesis of RA. Anti-cytokine agents that are currently available and those that are still in clinical trials have also been summarized. PMID- 26883281 TI - Effects of a long-term exercise programme on functional ability in people with dementia living in nursing homes: Research protocol of the LEDEN study, a cluster randomised controlled trial. AB - BACKGROUND: Exercise may lead to improvements on functional ability, physical function, and neuropsychiatric symptoms (particularly depression) in people with dementia (PWD). However, high-quality randomised controlled trial (RCT), controlling for the socialisation aspect of group-based exercise interventions, and designed to delay the declines on the functional ability of PWD in the nursing home (NH) setting is almost inexistent. This article describes the protocol of the LEDEN study, an exercise RCT for PWD living in NHs. METHODS/DESIGN: LEDEN is a cluster-randomised controlled pilot trial composed of two research arms: exercise training (experimental group) and social/recreational activity (control group). Both interventions will be provided twice a week, for 60 min, during the 6-month intervention. The total duration of the study is 12 months, being six months of intervention plus six months of observational follow up. Eight French NHs volunteered to participate in LEDEN; they have been randomised to either exercise intervention or social/recreational intervention in a 1:1 ratio. RESULTS: The primary objective is to investigate the effects of exercise, compared to a social/recreational intervention, on the ability of PWD living in NHs to perform activities of daily living (ADL). Secondary objectives are related with the cost-effectiveness of the interventions, and the effects of the interventions on patients' physical function, neuropsychiatric symptoms, pain, nutritional status, and the incidence of falls and fractures. DISCUSSION: LEDEN will provide the preliminary evidence needed to inform the development of larger and more complex interventions using exercise or non-exercise social interventions. PMID- 26883283 TI - Early intervention for depression and anxiety in 16-18-year-olds: Protocol for a feasibility cluster randomised controlled trial of open-access psychological workshops in schools (DISCOVER). AB - Adolescence is a vulnerable period for the development of mental health problems. The DISCOVER intervention aims to provide accessible, acceptable and cost effective psychological support for stressed adolescents in inner-city secondary schools. The intervention uses age-appropriate cognitive-behavioural therapy (CBT) methods and materials, delivered in an interactive 1-day workshop with additional telephone support. An open-access entry route allows students to self refer. This protocol describes a feasibility cluster randomised controlled trial (RCT) comparing DISCOVER with a waitlist control condition. The study will run across 10 clusters (secondary schools) in the inner London Boroughs of Southwark and Lambeth. Participants are students aged over 16years who are seeking help with anxiety and/or depressive symptoms. Key feasibility parameters relate to the proportion of students willing to participate in the research following publicity events; the proportion of students who complete the intervention; and response rates for outcome measures. Outcome variance estimates and intra-cluster correlations will be obtained for future power calculations. Qualitative methods will be used to explore the acceptability of the intervention and research procedures for students and school staff. The feasibility of an economic evaluation will also be examined. The results will (i) determine the appropriateness of proceeding to a definitive full-scale trial; and (ii) inform the development of an optimised version of the DISCOVER intervention that can be tested within feasible parameters. PMID- 26883282 TI - Distance learning strategies for weight management utilizing social media: A comparison of phone conference call versus social media platform. Rationale and design for a randomized study. AB - Management of obesity in the context of the primary care physician visit is of limited efficacy in part because of limited ability to engage participants in sustained behavior change between physician visits. Therefore, healthcare systems must find methods to address obesity that reach beyond the walls of clinics and hospitals and address the issues of lifestyle modification in a cost-conscious way. The dramatic increase in technology and online social networks may present healthcare providers with innovative ways to deliver weight management programs that could have an impact on health care at the population level. A randomized study will be conducted on 70 obese adults (BMI 30.0-45.0 kg/m(2)) to determine if weight loss (6 months) is equivalent between weight management interventions utilizing behavioral strategies by either a conference call or social media approach. The primary outcome, body weight, will be assessed at baseline and 6 months. Secondary outcomes including waist circumference, energy and macronutrient intake, and physical activity will be assessed on the same schedule. In addition, a cost analysis and process evaluation will be completed. PMID- 26883284 TI - In Memoriam: Paul I. Terasaki-September 10, 1929 to January 25, 2016. PMID- 26883285 TI - Design and Synthesis of Triangulated DNA Origami Trusses. AB - DNA nanotechnology offers unique control over matter on the nanoscale. Here, we extend the DNA origami method to cover a range of wireframe truss structures composed of equilateral triangles, which use less material per volume than standard multiple-helix bundles. From a flat truss design, we folded tetrahedral, octahedral, or irregular dodecahedral trusses by exchanging few connector strands. Other than standard origami designs, the trusses can be folded in low salt buffers that make them compatible with cell culture buffers. The structures also have defined cavities that may in the future be used to precisely position functional elements such as metallic nanoparticles or enzymes. Our graph routing program and a simple design pipeline will enable other laboratories to make use of this valuable and potent new construction principle for DNA-based nanoengineering. PMID- 26883286 TI - Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer. AB - Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28-0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25-0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p <= 0.007). PMID- 26883287 TI - Outcomes of 27 Gauge Microincision Vitrectomy Surgery for Posterior Segment Disease. PMID- 26883288 TI - Molecular phylogeny, pathogenicity and toxigenicity of Fusarium oxysporum f. sp. lycopersici. AB - The present study aimed at the molecular characterization of pathogenic and non pathogenic F. oxysporum f. sp. lycopersici strains isolated from tomato. The causal agent isolated from symptomatic plants and soil samples was identified based on morphological and molecular analyses. Pathogenicity testing of 69 strains on five susceptible tomato varieties showed 45% of the strains were highly virulent and 30% were moderately virulent. Molecular analysis based on the fingerprints obtained through ISSR indicated the presence of wide genetic diversity among the strains. Phylogenetic analysis based on ITS sequences showed the presence of at least four evolutionary lineages of the pathogen. The clustering of F. oxysporum with non pathogenic isolates and with the members of other formae speciales indicated polyphyletic origin of F. oxysporum f. sp. lycopersici. Further analysis revealed intraspecies variability and nucleotide insertions or deletions in the ITS region among the strains in the study and the observed variations were found to be clade specific. The high genetic diversity in the pathogen population demands for development of effective resistance breeding programs in tomato. Among the pathogenic strains tested, toxigenic strains harbored the Fum1 gene clearly indicating that the strains infecting tomato crops have the potential to produce Fumonisin. PMID- 26883289 TI - Gas Sensing with Bare and Graphene-covered Optical Nano-Antenna Structures. AB - The motivation behind this work is to study the gas phase chemical sensing characteristics of optical (plasmonic) nano-antennas (ONA) and graphene/graphene oxide-covered versions of these structures. ONA are devices that have their resonating frequency in the visible range. The basic principle governing the detection mechanism for ONA is refractive index sensing. The change in the concentration of the analyte results in a differing amount of adsorbate and correlated shifts in the resonance wavelength of the device. In this work, bare and graphene or graphene oxide covered ONA have been evaluated for gas sensing performance. Four different analytes (ethanol, acetone, nitrogen dioxide and toluene) were used in testing. ONA response behavior to different analytes was modified by adsorption within the graphene and graphene oxide overlayers. This work is a preliminary study to understand resonance wavelength shift caused by different analytes. Results imply that the combination of well-structured ONA functionalized by graphene-based adsorbers can give sensitive and selective sensors but baseline drift effects identified in this work must be addressed for applied measurements. PMID- 26883290 TI - Knockdown of chemokine receptor CXCR4 gene by RNA interference: Effects on the B16-F10 melanoma growth. AB - The incidence of malignant melanoma has increased greatly in recent decades presenting a high mortality rate despite intensive efforts in this area of research. Recent studies indicate that the chemokine receptor 4 (CXCR4) plays a critical role in cancer. Thus, it has been reported that CXCL12 binding to CXCR4 initiates various downstream signaling pathways that result in a plethora of responses involved in cell proliferation and metastasis. Recently, we demonstrated that CXCR4 silencing by RNA interference (RNAi) significantly reduced the number of pulmonary metastatic nodules. In the present study, we examined the effect of the intratumoral injection of CXCR4 short hairpin (shRNA) expressing plasmids on the growth of B16-F10 melanoma in mice. In vitro transfection of these tumor cells with CXCR4 shRNA expressing plasmid (CXCR4 shRNA) significantly reduced the levels of CXCR4 mRNA (85%) and CXCR4 protein (70%) compared with the control. We showed that the tumor growth was significantly reduced (66%) in mice inoculated with transfected B16-F10 melanoma cells when compared with the control group. We also found that the intratumoral injection of CXCR4 shRNA expressing plasmids results in a significant inhibition (70%) of B16-F10 melanoma growth. This finding supports the hypothesis that a direct administration of RNAi-based therapeutics into the target tumor is a promising approach for overcoming the hurdles of systemic delivery. The present study is the first demonstration that CXCR4 plays a critical role in B16-F10 melanoma growth. Currently there is great interest in the development of antagonists for therapeutic targeting CXCR4 expression. Considering our results and the fact that CXCR4 is highly conserved between human and mouse, this experimental model of cancer may be useful for the discovery of new CXCR4 antagonists with clinical implications. PMID- 26883291 TI - Numerical study of wall shear stress-based descriptors in the human left coronary artery. AB - The present work is about the application of wall shear stress descriptors - time averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residence time (RRT) - to the study of blood flow in the left coronary artery (LCA). These descriptors aid the prediction of disturbed flow conditions in the vessels and play a significant role in the detection of potential zones of atherosclerosis development. Hemodynamic descriptors data were obtained, numerically, through ANSYS(r) software, for the LCA of a patient-specific geometry and for a 3D idealized model. Comparing both cases, the results are coherent, in terms of location and magnitude. Low TAWSS, high OSI and high RRT values are observed in the bifurcation - potential zone of atherosclerosis appearance. The dissimilarities observed in the TAWSS values, considering blood as a Newtonian or non-Newtonian fluid, releases the importance of the correct blood rheologic caracterization. Moreover, for a higher Reynolds number, the TAWSS values decrease in the bifurcation and along the LAD branch, increasing the probability of plaques deposition. Furthermore, for a stenotic LCA model, very low TAWSS and high RRT values in front and behind the stenosis are observed, indicating the probable extension, in the flow direction, of the lesion. PMID- 26883292 TI - Growth of Continuous Monolayer Graphene with Millimeter-sized Domains Using Industrially Safe Conditions. AB - We demonstrate the growth of continuous monolayer graphene films with millimeter sized domains on Cu foils under intrinsically safe, atmospheric pressure growth conditions, suitable for application in roll-to-roll reactors. Previous attempts to grow large domains in graphene have been limited to isolated graphene single crystals rather than as part of an industrially useable continuous film. With both appropriate pre-treatment of the Cu and optimization of the CH4 supply, we show that it is possible to grow continuous films of monolayer graphene with millimeter scale domains within 80 min by chemical vapour deposition. The films are grown under industrially safe conditions, i.e., the flammable gases (H2 and CH4) are diluted to well below their lower explosive limit. The high quality, spatial uniformity, and low density of domain boundaries are demonstrated by charge carrier mobility measurements, scanning electron microscope, electron diffraction study, and Raman mapping. The hole mobility reaches as high as ~5,7002 m(2) V(-1) s(-1) in ambient conditions. The growth process of such high quality graphene with a low H2 concentration and short growth times widens the possibility of industrial mass production. PMID- 26883293 TI - Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1. AB - Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B. Production of H2O2 during redox transformation of NBD compounds is associated with the transition of a monomeric form of Cu/Zn superoxide dismutase 1 (SOD1) to stable dimers. The highly stable and functionally active SOD1 dimer, in the absence of adequate activities in downstream reactions, promotes the disproportionate production and accumulation of intracellular hydrogen peroxide shortly after exposure to NBD compounds. The intrinsic fluorescence of small compounds was used to demonstrate their binding to SOD1. Our data indicate that H2O2 and concomitantly generated electrophilic intermediates behave as independent entities, but all contribute to the biological reactivity of NBD compounds. This study opens a promising path to identify new biomarkers of oxidative/electrophilic stress in the progression of cancer and other diseases. PMID- 26883294 TI - Brain regulation of food craving: relationships with weight status and eating behavior. AB - OBJECTIVES: Food craving is a driving force for overeating and obesity. However, the relationship between brain mechanisms involved in its regulation and weight status is still an open issue. Gaps in the studied body mass index (BMI) distributions and focusing on linear analyses might have contributed to this lack of knowledge. Here, we investigated brain mechanisms of craving regulation using functional magnetic resonance imaging in a balanced sample including normal weight, overweight and obese participants. We investigated associations between characteristics of obesity, eating behavior and regulatory brain function focusing on nonlinear relationships. SUBJECTS/METHODS: Forty-three hungry female volunteers (BMI: 19.4-38.8 kg m(-2), mean: 27.5+/-5.3 s.d.) were presented with visual food stimuli individually pre-rated according to tastiness and healthiness. The participants were instructed to either admit to the upcoming craving or regulate it. We analyzed the relationships between regulatory brain activity as well as functional connectivity and BMI or eating behavior (Three Factor Eating Questionnaire, scales: Cognitive Restraint, Disinhibition). RESULTS: During regulation, BMI correlated with brain activity in the left putamen, amygdala and insula in an inverted U-shaped manner. Functional connectivity between the putamen and the dorsolateral prefrontal cortex (dlPFC) correlated positively with BMI, whereas that of amygdala with pallidum and lingual gyrus was nonlinearly (U-shaped) associated with BMI. Disinhibition correlated negatively with the strength of functional connectivity between amygdala and dorsomedial prefrontal (dmPFC) cortex as well as caudate. CONCLUSIONS: This study is the first to reveal quadratic relationships of food related brain processes and BMI. Reported nonlinear associations indicate inverse relationships between regulation-related motivational processing in the range of normal weight/overweight compared with the obese range. Connectivity analyses suggest that the need for top-down (dlPFC) adjustment of striatal value representations increases with BMI, whereas the interplay of self-monitoring (dmPFC) or eating-related strategic action planning (caudate) and salience processing (amygdala) might be hampered with high Disinhibition. PMID- 26883296 TI - Simulations and Social Empathy: Domestic Violence Education in the New Millennium. AB - When teaching about domestic violence, we hope that our students will be moved to act and organize against it within a social justice framework. We argue that instructional simulations can be used to inspire students to do so. Instructional simulations and gaming tools have been part of higher education pedagogical tool kits since at least the 1960s. Yet it is only recently that a domestic violence resource exists that reflects the interdisciplinary, interactive, and empathy building orientation of feminist pedagogy. Drawing on the concept of "social empathy," we analyze the potential of the instructional simulation "In Her Shoes," developed by the Washington State Coalition Against Domestic Violence, to help students gain knowledge of and empathy for the constrained choices facing battered women, understand the frequent disjuncture between leaving and safety, and close the gap between cultural perceptions and lived realities. PMID- 26883297 TI - It's Her Fault: Student Acceptance of Rape Myths On Two College Campuses. AB - The present study examined factors that are associated with an individual's adherence to rape myths at two colleges located in the same town. Particularly, we examined sex, race, and participants' drinking behavior in relation to rape myth acceptance. We found that males and heavy drinkers are more likely than females and non/low drinkers to adhere to rape myths. An interaction between males and drinking was also found indicating a moderated effect of gender on rape myth acceptance. In addition, the college with sexual assault programming did not experience a lowered acceptance of rape myths compared with the college with no programming. PMID- 26883295 TI - A collagen-binding EGFR antibody fragment targeting tumors with a collagen-rich extracellular matrix. AB - Many tumors over-express collagen, which constitutes the physical scaffold of tumor microenvironment. Collagen has been considered to be a target for cancer therapy. The collagen-binding domain (CBD) is a short peptide, which could bind to collagen and achieve the sustained release of CBD-fused proteins in collagen scaffold. Here, a collagen-binding EGFR antibody fragment was designed and expressed for targeting the collagen-rich extracellular matrix in tumors. The antibody fragment (Fab) of cetuximab was fused with CBD (CBD-Fab) and expressed in Pichia pastoris. CBD-Fab maintained antigen binding and anti-tumor activity of cetuximab and obtained a collagen-binding ability in vitro. The results also showed CBD-Fab was mainly enriched in tumors and had longer retention time in tumors in A431 s.c. xenografts. Furthermore, CBD-Fab showed a similar therapeutic efficacy as cetuximab in A431 xenografts. Although CBD-Fab hasn't showed better therapeutic effects than cetuximab, its smaller molecular and special target may be applicable as antibody-drug conjugates (ADC) or immunotoxins. PMID- 26883298 TI - Time course and factors predicting arterial stiffness reversal in patients with aldosterone-producing adenoma after adrenalectomy: prospective study of 102 patients. AB - Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (DeltaDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (DeltabaPWV0-6mo). The associated factors of the change in haPWV at 6 months (DeltahaPWV0-6mo) were baseline haPWV, DeltaDBP0 6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors. PMID- 26883299 TI - Prevalence and predictors of pediatric disclosure among HIV-infected Nigerian children on treatment. AB - This cross-sectional, facility-based study aimed to determine the prevalence, age, and main agent of disclosure among Nigerian children on antiretroviral therapy. It also sought to elicit barriers to, and facilitators of disclosure; and any association between disclosure and health outcomes. A semi-structured questionnaire was administered to 110 parents/caregivers of children >=6 years. CD4 count, viral load, opportunistic infections and adherence information were also extracted from medical records for all 110 children. The mean age of the children in the study was 10.15 years (SD = 2.97), with a median (range) of 9.50 (6-18) years. According to parents/caregivers' accounts, 34 (30.9%) children knew that they were living with HIV, while 74 (67.3%) did not know. Mean age at disclosure was 10.47 years (SD = 2.62), with a median (range) of 10.00 (6-17) years. Most children (79.4%) were disclosed at home by their parent(s)/caregiver. The rest were disclosed at the hospital: five were disclosed by a healthcare provider, while two were accidentally disclosed. The most common reasons for disclosure were related to adherence issues - either to help prepare the children to take their medicines or that the child had refused to take his/her medicines (39.4%). This was followed by the child asking a lot of questions related to his/her health, frequent visits to the hospital, or why s/he was taking a lot of medicines even though s/he did not feel ill (27.3%). Most parents/caregivers did not disclose because the child was considered too young (84.0%) or will not be able to keep their HIV status a secret (10.7%). Multivariate logistic regression showed that only child's age was a statistically significant predictor of status disclosure (OR 1.69, p = .002; 95% CI 1.21-2.34). There was no association between disclosure and self-reported adherence (p = .615). PMID- 26883300 TI - Doctor of physical therapy students' attitudes towards people with disabilities: a descriptive study. AB - Purpose To describe attitudes of doctoral physical therapy (DPT) students towards people with disability and examine predictive ability of demographic variables on those attitudes. Methods Two established surveys, Attitudes Towards Disabled Persons-Form O (ATDP-O) and Disability Attitudes in Health Care (DAHC) were completed by first (Y1) and third year (Y3) students in a DPT programme. Demographics and information about students' contact experience with people with disabilities were collected through a brief questionnaire. Multiple linear regression models were constructed from predictor variables. Results Scores on the ATDP-O and the DAHC were not significantly different between the Y1 and Y3 DPT students. There was a modest correlation (r = 0.342, p < 0.001) between the ATDP-O and the DAHC. Being female and having work contact with people with disabilities both explained about 9% of the variance in the DAHC; while having a close family member explains about 4% of the variance in the ATDP-O. Conclusion Attitudes of DPT students over the course of their education did not change. The DAHC is a more recently developed tool and should continue to be investigated for its usefulness in healthcare professional students. Faculty should consider measuring attitudes and developing specific educational strategies to improve attitudes with the goal to improve patient care. Implications for Rehabilitation Attitudes towards people with disability can impact their health care. Physical therapy students, in general, express positive attitudes towards people with disabilities and no differences in attitudes were determined in a group of Year 1 and Year 3 doctoral physical therapy students. Opportunities exist to intentionally thread educational strategies throughout a professional curriculum to facilitate further development of positive attitudes in doctoral physical therapy students. PMID- 26883301 TI - Differentiation with elaidate tends to impair insulin-dependent glucose uptake and GLUT4 translocation in 3T3-L1 adipocytes. AB - Development of type 2 diabetes mellitus and insulin resistance is associated with a quality of dietary fatty acids such as saturated and unsaturated fatty acids. Dietary fatty acids also include transform of unsaturated fatty acids and intake of transform of oleate (elaidate) is associated with cardiovascular disease. However, little is known about the roles of elaidate in insulin responsiveness. We show here that elaidate impairs insulin-dependent glucose uptake in adipocytes. Differentiation with 10 MUM elaidate, which is close to physiological plasma concentration, reduces insulin-dependent glucose uptake. Furthermore, insulin-dependent GLUT4 translocation is disturbed in adipocytes differentiated with elaidate. In addition, analysis of lipolysis and gene expression shows that deteriorative effects of elaidate on insulin responsiveness are limited but not general. Thus, our findings reveal that differentiation with elaidate tends to affect insulin-dependent glucose uptake through alternation of GLUT4 translocation from cytosol to the plasma membrane. PMID- 26883302 TI - Hip and knee net joint moments that correlate with success in lateral load transfers over a low friction surface. AB - We previously described two different preferred strategies used to perform a lateral load transfer. The wide stance strategy was not used successfully on a low-friction surface, while the narrow stance strategy was successful. Here, we retrospectively examined lower extremity net joint moments between successful and unsuccessful strategies to determine if there is a kinetic benefit consideration that may go into choosing the preferred strategy. Success vs. failure over a novel slippery surface was used to dichotomise 35 healthy working-age individuals into the two groups (successful and unsuccessful). Participants performed lateral load transfers over three sequential surface conditions: high friction, novel low friction and practised low friction. The unsuccessful strategy required larger start torques, but lower dynamic moments during transfer compared to the successful strategy. These results indicate that the periodically unsuccessful strategy may be preferred because it requires less muscle recruitment and lower stresses on lower extremity soft tissues. Practitioner Summary: The reason for this paper is to retrospectively examine the joint moment in two different load transfer strategies that are used in a lateral load transfer. We found that periodically unsuccessful strategies that we previously reported may be a beneficial toward reduced lower extremity joint stresses. PMID- 26883303 TI - Utilizing intentional internal resonance to achieve multi-harmonic atomic force microscopy. AB - During dynamic atomic force microscopy (AFM), the deflection of a scanning cantilever generates multiple frequency terms due to the nonlinear nature of AFM tip-sample interactions. Even though each frequency term is reasonably expected to encode information about the sample, only the fundamental frequency term is typically decoded to provide topographic mapping of the measured surface. One of main reasons for discarding higher harmonic signals is their low signal-to-noise ratio. Here, we introduce a new design concept for multi-harmonic AFM, exploiting intentional nonlinear internal resonance for the enhancement of higher harmonics. The nonlinear internal resonance, triggered by the non-smooth tip-sample dynamic interactions, results in nonlinear energy transfers from the directly excited fundamental bending mode to the higher-frequency mode and, hence, enhancement of the higher harmonic of the measured response. It is verified through detailed theoretical and experimental study that this AFM design can robustly incorporate the required internal resonance and enable high-frequency AFM measurements. Measurements on an inhomogeneous polymer specimen demonstrate the efficacy of the proposed design, namely that the higher harmonic of the measured response is capable of enhanced simultaneous topography imaging and compositional mapping, exhibiting less crosstalk with an abrupt height change. PMID- 26883304 TI - Transfer of useful variability of high grain iron and zinc from Aegilops kotschyi into wheat through seed irradiation approach. AB - PURPOSE: To transfer the 2S chromosomal fragment(s) of Aegilops kotschyi (2S(k)) into the bread wheat genome which could lead to the biofortification of wheat with high grain iron and zinc content. MATERIALS AND METHODS: Wheat-Ae. kotschyi 2A/2S(k) substitution lines with high grain iron and zinc content were used to transfer the gene/loci for high grain Fe and Zn content into wheat using seed irradiation approach. RESULTS: Bread wheat plants derived from 40 krad-irradiated seeds showed the presence of univalents and multivalents during meiotic metaphase I. Genomic in situ hybridization analysis of seed irradiation hybrid F2 seedlings showed several terminal and interstitial signals indicated the introgression of Ae. kotschyi chromosome segments. This proves the efficacy of seed radiation hybrid approach in gene transfer experiments. All the radiation-treated hybrid plants with high grain Fe and Zn content were analyzed with wheat group 2 chromosome-specific polymorphic simple sequence repeat markers to identify the introgression of small alien chromosome fragment(s). CONCLUSION: Radiation induced hybrids showed more than 65% increase in grain iron and 54% increase in Zn contents with better harvest index than the elite wheat cultivar WL711 indicating effective and compensating translocations of 2S(k) fragments into wheat genome. PMID- 26883305 TI - Cannabis use in people with severe mental illness: The association with physical and mental health--a cohort study. A Pharmacotherapy Monitoring and Outcome Survey study. AB - OBJECTIVE: In the general population cannabis use is associated with better cardiometabolic outcomes. Patients with severe mental illness frequently use cannabis, but also present increased cardiometabolic risk factors. We explore the association between cannabis use and cardiometabolic risk factors in patients with severe mental illness. METHOD: A total of 3169 patients with severe mental illness from a Dutch cohort were included in the study. The association of cannabis use with body mass index, waist circumference, blood pressure, cholesterol, triglycerides, glucose, glycated hemoglobin and Positive and Negative Syndrome Scale was examined with separate univariate AN(C)OVA. Changes in metabolic risk factors and Positive and Negative Syndrome Scale were examined after a follow-up interval of 9-24 months, for patients who continued, discontinued, started or were never using cannabis between the two assessments. RESULTS: Cannabis users at baseline had lower body mass index, smaller waist circumference, lower diastolic blood pressure, and more severe psychotic symptoms than non-users. Patients who discontinued their cannabis use after the first assessment had a greater increase in body mass index, waist circumference, diastolic blood pressure and triglyceride concentrations than other patients, and the severity of their psychotic symptoms had decreased more compared to continued users and non-users. CONCLUSION: Extra attention should be paid to the monitoring and treatment of metabolic parameters in patients who discontinue their cannabis use. PMID- 26883307 TI - Evaluating the effectiveness of selected community-level interventions on key maternal, child health, and prevention of mother-to-child transmission of HIV outcomes in three countries (the ACCLAIM Project): a study protocol for a randomized controlled trial. AB - BACKGROUND: Efforts to scale up and improve programs for prevention of mother-to child transmission of HIV (PMTCT) have focused primarily at the health facility level, and limited attention has been paid to defining an effective set of community interventions to improve demand and uptake of services and retention. Many barriers to PMTCT are also barriers to pregnancy, childbirth, and postnatal care faced by mothers regardless of HIV status. Demand for maternal and child health (MCH) and PMTCT services can be limited by critical social, cultural, and structural barriers. Yet, rigorous evaluation has shown limited evidence of effectiveness of multilevel community-wide interventions aimed at improving MCH and HIV outcomes for pregnant women living with HIV. We propose to assess the effect of a package of multilevel community interventions: a social learning and action component, community dialogues, and peer-led discussion groups, on the demand for, uptake of, and retention of HIV positive pregnant/postpartum women in MCH/PMTCT services. METHODS/DESIGN: This study will undertake a three-arm randomized trial in Swaziland, Uganda, and Zimbabwe. Districts/regions (n = 9) with 45 PMTCT-implementing health facilities and their catchment areas (populations 7,300-27,500) will be randomly allocated to three intervention arms: 1) community leader engagement, 2) community leader engagement with community days, or 3) community leader engagement with community days and male and female community peer groups. The primary study outcome is HIV exposed infants (HEIs) returning to the health facility within 2 months for early infant diagnosis (EID) of HIV. Secondary study outcomes include gestational age of women attending for first antenatal care, male partners tested for HIV, and HEIs receiving nevirapine prophylaxis at birth. Changes in community knowledge, attitudes, practices, and beliefs on MCH/PMTCT will be assessed through household surveys. DISCUSSION: Implementation of the protocol necessitated changes in the original study design. We purposively selected facilities in the districts/regions though originally the study clusters were to be randomly selected. Lifelong antiretroviral therapy for all HIV positive pregnant and lactating women, Option B+, was implemented in the three countries during the study period, with the potential for a differential impact by study arm. Implementation however, was rapidly done across the districts/regions, so that there is unlikely be this potential confounding. We developed a system of monitoring and documentation of potential confounding activities or actions, and these data will be incorporated into analyses at the conclusion of the project. Strengthens of the study are that it tests multilevel interventions, utilizes program as well as study specific and individual data, and it is conducted under "real conditions" leading to more robust findings. Limitations of the protocol include the lack of a true control arm and inadequate control for the potential effect of Option B+, such as the intensification of messages as the importance of early ANC and male partner testing. TRIAL REGISTRATION: ClinicalTrials.gov (study ID: NCT01971710) Protocol version 5, 30 July 2013, registered 13 August 2013. PMID- 26883308 TI - A ban on smoking in psychiatric hospitals would reduce self burn injuries. PMID- 26883309 TI - Assembly of nothing: equilibrium fluids with designed structured porosity. AB - Controlled micro- to meso-scale porosity is a common materials design goal with possible applications ranging from molecular gas adsorption to particle size selective permeability or solubility. Here, we use inverse methods of statistical mechanics to design an isotropic pair interaction that, in the absence of an external field, assembles particles into an inhomogeneous fluid matrix surrounding pores of prescribed size ordered in a lattice morphology. The pore size can be tuned via modification of temperature or particle concentration. Moreover, modulating density reveals a rich series of microphase-separated morphologies including pore- or particle-based lattices, pore- or particle-based columns, and bicontinuous or lamellar structures. Sensitivity of pore assembly to the form of the designed interaction potential is explored. PMID- 26883310 TI - Cationic sulfonium functionalization renders Znsalens with high fluorescence, good water solubility and tunable cell-permeability. AB - In this study, we report for the first time that incorporation of cationic sulfonium to the Znsalens skeleton achieves water soluble fluorescent metal complex probes for living cell imaging. To circumvent Znsalen aggregation arising from intermolecular ZnO interactions (found between Zn and the phenoxyl group of another Znsalen molecule), we synthesized a series of sulfonium Znsalens based on alkylation of the 3-thioether or 3,5-dithioether moieties of salicylaldehydes. Such functionalization not only provides positive charge(s) to enhance electrostatic repulsion, but also increases steric hindrance, which renders the Znsalen complex water soluble as a monomeric species in aqueous media as revealed by diffusion ordered NMR spectroscopy (DOSY). More interestingly, these sulfonium Znsalens display "switched on" fluorescence when compared to thioether analogues, which was attributed to the electron-withdrawing sulfonium moiety that perturbs the photoinduced electron transfer (PET) process as suggested by computational calculations based on time-dependent density functional theory (TD-DFT). Most interestingly, live cell imaging experiments showed that modulation of the sulfonium moieties, such as the number or alkyl substituents, significantly tunes the cell-permeability of the fluorescent Znsalens. Thus, this study has demonstrated the importance of sulfonium functionalization on dissociating the intermolecular metal-ligand interactions and thus, modulating water solubility, photophysical properties and even cell-permeability of the fluorophores, which provides a new approach to the design of functional metal complexes for biological studies. PMID- 26883311 TI - Drug-resistant tuberculosis plagues India. PMID- 26883312 TI - Bullying still rife in medical training. PMID- 26883313 TI - Winter road safety is no accident. PMID- 26883314 TI - Online tools improve mental health in primary care. PMID- 26883315 TI - Spontaneous migration of an implanted central venous access device into the ipsilateral jugular vein. PMID- 26883316 TI - Routinely collected data and comparative effectiveness evidence: promises and limitations. PMID- 26883317 TI - Guiding the reporting of studies that use routinely collected health data. PMID- 26883318 TI - National and Regional Representativeness of Hospital Emergency Department Visit Data in the National Syndromic Surveillance Program, United States, 2014. AB - OBJECTIVE: We examined the representativeness of the nonfederal hospital emergency department (ED) visit data in the National Syndromic Surveillance Program (NSSP). METHODS: We used the 2012 American Hospital Association Annual Survey Database, other databases, and information from state and local health departments participating in the NSSP about which hospitals submitted data to the NSSP in October 2014. We compared ED visits for hospitals submitting data with all ED visits in all 50 states and Washington, DC. RESULTS: Approximately 60.4 million of 134.6 million ED visits nationwide (~45%) were reported to have been submitted to the NSSP. ED visits in 5 of 10 regions and the majority of the states were substantially underrepresented in the NSSP. The NSSP ED visits were similar to national ED visits in terms of many of the characteristics of hospitals and their service areas. However, visits in hospitals with the fewest annual ED visits, in rural trauma centers, and in hospitals serving populations with high percentages of Hispanics and Asians were underrepresented. CONCLUSIONS: NSSP nonfederal hospital ED visit data were representative for many hospital characteristics and in some geographic areas but were not very representative nationally and in many locations. Representativeness could be improved by increasing participation in more states and among specific types of hospitals. (Disaster Med Public Health Preparedness. 2016;10:562-569). PMID- 26883319 TI - Proactive response inhibition abnormalities in the sensorimotor cortex of patients with schizophrenia. AB - BACKGROUND: Previous studies of response inhibition in patients with schizophrenia have focused on reactive inhibition tasks (e.g., stop-signal, go/no go), primarily observing lateral prefrontal cortex abnormalities. However, recent studies suggest that purposeful and sustained (i.e., proactive) inhibition may also be affected in these patients. METHODS: Patients with chronic schizophrenia and healthy controls underwent fMRI while inhibiting motor responses during multisensory (audiovisual) stimulation. Resting state data were also collected. RESULTS: We included 37 patients with schizophrenia and 37 healthy controls in our study. Both controls and patients with schizophrenia successfully inhibited the majority of overt motor responses. Functional results indicated basic inhibitory failure in the lateral premotor and sensorimotor cortex, with opposing patterns of positive (schizophrenia) versus negative (control) activation. Abnormal activity was associated with independently assessed signs of psychomotor retardation. Patients with schizophrenia also exhibited unique activation of the pre-supplementary motor area (pre-SMA)/SMA and precuneus relative to baseline as well as a failure to deactivate anterior nodes of the default mode network. Independent resting-state connectivity analysis indicated reduced connectivity between anterior (task results) and posterior regions of the sensorimotor cortex for patients as well as abnormal connectivity between other regions (cerebellum, thalamus, posterior cingulate gyrus and visual cortex). LIMITATIONS: Aside from rates of false-positive responses, true proactive response inhibition tasks do not provide behavioural metrics that can be independently used to quantify task performance. CONCLUSION: Our results suggest that basic cortico-cortico and intracortical connections between the sensorimotor cortex and adjoining regions are impaired in patients with schizophrenia and that these impaired connections contribute to inhibitory failures (i.e., a positive rather than negative hemodynamic response). PMID- 26883320 TI - Collaborating with a social housing provider supports a large cohort study of the health effects of housing conditions. AB - BACKGROUND: Despite the importance of adequate, un-crowded housing as a prerequisite for good health, few large cohort studies have explored the health effects of housing conditions. The Social Housing Outcomes Worth (SHOW) Study was established to assess the relationship between housing conditions and health, particularly between household crowding and infectious diseases. This paper reports on the methods and feasibility of using a large administrative housing database for epidemiological research and the characteristics of the social housing population. METHODS: This prospective open cohort study was established in 2003 in collaboration with Housing New Zealand Corporation which provides housing for approximately 5% of the population. The Study measures health outcomes using linked anonymised hospitalisation and mortality records provided by the New Zealand Ministry of Health. RESULTS: It was possible to match the majority (96%) of applicant and tenant household members with their National Health Index (NHI) number allowing linkage to anonymised coded data on their hospitalisations and mortality. By December 2011, the study population consisted of 11,196 applicants and 196,612 tenants. Half were less than 21 years of age. About two-thirds identified as Maori or Pacific ethnicity. Household incomes were low. Of tenant households, 44% containing one or more smokers compared with 33% for New Zealand as a whole. Exposure to household crowding, as measured by a deficit of one or more bedrooms, was common for applicants (52%) and tenants (38%) compared with New Zealanders as whole (10%). CONCLUSIONS: This project has shown that an administrative housing database can be used to form a large cohort population and successfully link cohort members to their health records in a way that meets confidentiality and ethical requirements. This study also confirms that social housing tenants are a highly deprived population with relatively low incomes and high levels of exposure to household crowding and environmental tobacco smoke. PMID- 26883321 TI - Parenthood in transition - Somali-born parents' experiences of and needs for parenting support programmes. AB - BACKGROUND: Pre- and post-migration trauma due to forced migration may impact negatively on parents' ability to care for their children. Little qualitative work has examined Somali-born refugees' experiences. The aim of this study is to explore Somali-born refugees' experiences and challenges of being parents in Sweden, and the support they need in their parenting. METHODS: A qualitative descriptive study was undertaken. Data were collected from four focus group discussions (FGDs) among 23 Somali-born mothers and fathers living in a county in central Sweden. Qualitative content analysis has been applied. RESULTS: A main category, Parenthood in Transition, emerged as a description of a process of parenthood in transition. Two generic categories were identified: Challenges, and Improved parenting. Challenges emerged from leaving the home country and being new and feeling alienated in the new country. In Improved parenting, an awareness of opportunities in the new country and ways to improve their parenting was described, which includes how to improve their communication and relationship with their children. The parents described a need for information on how to culturally adapt their parenting and obtain support from the authorities. CONCLUSIONS: Parents experienced a process of parenthood in transition. They were looking to the future and for ways to improve their parenting. Schools and social services can overcome barriers that prevent lack of knowledge about the new country's systems related to parenthood. Leaving the home country often means separation from the family and losing the social network. We suggest that staff in schools and social services offer parent training classes for these parents throughout their children's childhood, with benefits for the child and family. PMID- 26883322 TI - Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair. AB - BACKGROUND: An attempt was made to reprogram peripheral blood cells into human induced pluripotent stem cell (hiPSCs) as a new cell source for cartilage repair. METHODS: We generated chondrogenic lineage from human peripheral blood via hiPSCs using an integration-free method. Peripheral blood cells were either obtained from a human blood bank or freshly collected from volunteers. After transforming peripheral blood cells into iPSCs, the newly derived iPSCs were further characterized through karyotype analysis, pluripotency gene expression and cell differentiation ability. iPSCs were differentiated through multiple steps, including embryoid body formation, hiPSC-mesenchymal stem cell (MSC)-like cell expansion, and chondrogenic induction for 21 days. Chondrocyte phenotype was then assessed by morphological, histological and biochemical analysis, as well as the chondrogenic expression. RESULTS: hiPSCs derived from peripheral blood cells were successfully generated, and were characterized by fluorescent immunostaining of pluripotent markers and teratoma formation in vivo. Flow cytometric analysis showed that MSC markers CD73 and CD105 were present in monolayer cultured hiPSC MSC-like cells. Both alcian blue and toluidine blue staining of hiPSC-MSC chondrogenic pellets showed as positive. Immunohistochemistry of collagen II and X staining of the pellets were also positive. The sulfated glycosaminoglycan content was significantly increased, and the expression levels of the chondrogenic markers COL2, COL10, COL9 and AGGRECAN were significantly higher in chondrogenic pellets than in undifferentiated cells. These results indicated that peripheral blood cells could be a potential source for differentiation into chondrogenic lineage in vitro via generation of mesenchymal progenitor cells. CONCLUSIONS: This study supports the potential applications of utilizing peripheral blood cells in generating seed cells for cartilage regenerative medicine in a patient-specific and cost-effective approach. PMID- 26883323 TI - Spatiotemporal hierarchy in antibody recognition against transmitted HIV-1 envelope glycoprotein during natural infection. AB - BACKGROUND: Majority of HIV-1 infection is established by one transmitted/founder virus and understanding how the neutralizing antibodies develop against this virus is critical for our rational design an HIV-1 vaccine. RESULTS: We report here antibody profiling of sequential plasma samples against transmitted/founder HIV-1 envelope glycoprotein in an epidemiologically linked transmission pair using our previously reported antigen library approach. We have decomposed the antibody recognition into three major subdomains on the envelope and showed their development in vivo followed a spatiotemporal hierarchy: starting with the ectodomain of gp41 at membrane proximal region, then the V3C3V4 and the V1V2 of gp120 at the membrane distal region. While antibodies to these subdomains appeared to undergo avidity maturation, the early anti-gp41 antibodies failed to translate into detectable autologous neutralization. Instead, it was the much delayed anti-V3C3V4 and anti-V1V2 antibodies constituted the major neutralizing activities. CONCLUSIONS: Our results indicate that the initial antibody response was severely misguided by the transmitted/founder virus and future vaccine design would need to avoid the ectodomain of gp41 and focus on the neutralizing targets in the V3C3V4 and V1V2 subdomains of gp120. PMID- 26883325 TI - Erratum to: Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of olaparib in breast cancer cells: a proof of concept study for synthetic lethal therapeutic option. PMID- 26883324 TI - Small scale homelike special care units and traditional special care units: effects on cognition in dementia; a longitudinal controlled intervention study. AB - BACKGROUND: Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. METHODS: A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. RESULTS: Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. CONCLUSIONS: While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition. PMID- 26883326 TI - An analysis of human microbe-disease associations. AB - The microbiota living in the human body has critical impacts on our health and disease, but a systems understanding of its relationships with disease remains limited. Here, we use a large-scale text mining-based manually curated microbe disease association data set to construct a microbe-based human disease network and investigate the relationships between microbes and disease genes, symptoms, chemical fragments and drugs. We reveal that microbe-based disease loops are significantly coherent. Microbe-based disease connections have strong overlaps with those constructed by disease genes, symptoms, chemical fragments and drugs. Moreover, we confirm that the microbe-based disease analysis is able to predict novel connections and mechanisms for disease, microbes, genes and drugs. The presented network, methods and findings can be a resource helpful for addressing some issues in medicine, for example, the discovery of bench knowledge and bedside clinical solutions for disease mechanism understanding, diagnosis and therapy. PMID- 26883328 TI - Quantification of deep medullary veins at 7 T brain MRI. AB - OBJECTIVES: Deep medullary veins support the venous drainage of the brain and may display abnormalities in the context of different cerebrovascular diseases. We present and evaluate a method to automatically detect and quantify deep medullary veins at 7 T. METHODS: Five participants were scanned twice, to assess the robustness and reproducibility of manual and automated vein detection. Additionally, the method was evaluated on 24 participants to demonstrate its application. Deep medullary veins were assessed within an automatically created region-of-interest around the lateral ventricles, defined such that all veins must intersect it. A combination of vesselness, tubular tracking, and hysteresis thresholding located individual veins, which were quantified by counting and computing (3-D) density maps. RESULTS: Visual assessment was time-consuming (2 h/scan), with an intra-/inter-observer agreement on absolute vein count of ICC = 0.76 and 0.60, respectively. The automated vein detection showed excellent inter scan reproducibility before (ICC = 0.79) and after (ICC = 0.88) visually censoring false positives. It had a positive predictive value of 71.6 %. CONCLUSION: Imaging at 7 T allows visualization and quantification of deep medullary veins. The presented method offers fast and reliable automated assessment of deep medullary veins. KEY POINTS: * Deep medullary veins support the venous drainage of the brain * Abnormalities of these veins may indicate cerebrovascular disease and quantification is needed * Automated methods can achieve this and support human observers * The presented method provides robust and reproducible detection of veins * Intuitive quantification is provided via count and venous density maps. PMID- 26883327 TI - A meta-analysis of diffusion-weighted and gadoxetic acid-enhanced MR imaging for the detection of liver metastases. AB - OBJECTIVES: To obtain the diagnostic performance of diffusion-weighted (DW) and gadoxetic-enhanced magnetic resonance (MR) imaging in the detection of liver metastases. METHODS: A comprehensive search (EMBASE, PubMed, Cochrane) was performed to identify relevant articles up to June 2015. Inclusion criteria were: liver metastases, DW-MR imaging and/or gadoxetic acid-enhanced MR imaging, and per-lesion statistics. The reference standard was histopathology, intraoperative observation and/or follow-up. Sources of bias were assessed using the QUADAS-2 tool. A linear mixed-effect regression model was used to obtain sensitivity estimates. RESULTS: Thirty-nine articles were included (1,989 patients, 3,854 metastases). Sensitivity estimates for DW-MR imaging, gadoxetic acid-enhanced MR imaging and the combined sequence for detecting liver metastases on a per-lesion basis was 87.1 %, 90.6 % and 95.5 %, respectively. Sensitivity estimates by gadoxetic acid-enhanced MR imaging and the combined sequence were significantly better than DW-MR imaging (p = 0.0001 and p < 0.0001, respectively), and the combined MR sequence was significantly more sensitive than gadoxetic acid enhanced MR imaging (p < 0.0001). Similar results were observed in articles that compared the three techniques simultaneously, with only colorectal liver metastases and in liver metastases smaller than 1 cm. CONCLUSIONS: In patients with liver metastases, combined DW-MR and gadoxetic acid-enhanced MR imaging has the highest sensitivity for detecting liver metastases on a per-lesion basis. KEY POINTS: * DW-MRI is less sensitive than gadoxetic acid-enhanced MRI for detecting liver metastases * DW-MRI and gadoxetic acid-enhanced MRI is the best combination * Same results are observed in colorectal liver metastases * Same results are observed in liver metastases smaller than 1 cm * Same results are observed when histopathology alone is the reference standard. PMID- 26883329 TI - Restaging oesophageal cancer after neoadjuvant therapy with (18)F-FDG PET-CT: identifying interval metastases and predicting incurable disease at surgery. AB - OBJECTIVES: It is unknown whether restaging oesophageal cancer after neoadjuvant therapy with positron emission tomography-computed tomography (PET-CT) is more sensitive than contrast-enhanced CT for disease progression. We aimed to determine this and stratify risk. METHODS: This was a retrospective study of patients staged before neoadjuvant chemotherapy (NAC) by (18)F-FDG PET-CT and restaged with CT or PET-CT in a single centre (2006-2014). RESULTS: Three hundred and eighty-three patients were restaged (103 CT, 280 PET-CT). Incurable disease was detected by CT in 3 (2.91 %) and PET-CT in 17 (6.07 %). Despite restaging unsuspected incurable disease was encountered at surgery in 34/336 patients (10.1 %). PET-CT was more sensitive than CT (p = 0.005, McNemar's test). A new classification of FDG-avid nodal stage (mN) before NAC (plus tumour FDG-avid length) predicted subsequent progression, independent of conventional nodal stage. The presence of FDG-avid nodes after NAC and an impassable tumour stratified risk of incurable disease at surgery into high (75.0 %; both risk factors), medium (22.4 %; either), and low risk (3.87 %; neither) groups (p < 0.001). Decision theory supported restaging PET-CT. CONCLUSIONS: PET-CT is more sensitive than CT for detecting interval progression; however, it is insufficient in at least higher risk patients. mN stage and response (mNR) plus primary tumour characteristics can stratify this risk simply. KEY POINTS: * Restaging (18) F-FDG PET-CT after neoadjuvant chemotherapy identifies metastases in 6 % of patients * Restaging (18) F-FDG-PET-CT is more sensitive than CT for detecting interval progression * Despite this, at surgery 10 % of patients had unsuspected incurable disease * New concepts (FDG-avid nodal stage and response) plus tumour impassability stratify risk * Higher risk (if not all) patients may benefit from additional restaging modalities. PMID- 26883330 TI - Single-phase DECT with VNCT compared with three-phase CTU in patients with haematuria. AB - OBJECTIVE: To retrospectively evaluate the diagnostic performance of single-phase dual-energy CT (DECT) with virtual non-contrast CT (VNCT) compared with three phase CT urography (CTU) in patients with haematuria. METHODS: A total of 296 patients underwent three-phase CTU (NCT at 120 kVp; nephrographic phase and excretory phase DECTs at 140 kVp and 80 kVp) owing to haematuria. Diagnostic performances of CT scans were compared for detecting urothelial tumours and urinary stones. Dose-length product (DLP) was compared in relation to single phase DECT and three-phase CTU Dose-length product (DLP) was compared in relation to single-phase DECT and three-phase CTU. RESULTS: Sensitivity and specificity for tumour were 95 % (19/20) and 98.9 % (273/276) on CTU, 95 % (19/20) and 98.2 % (271/276) on nephrographic phase DECT, and 90 % (18/20) and 98.2 % (271/276) on excretory phase DECT (P > 0.1). Of the 148 stones detected on NCT, 108 (73 %) and 100 (67.6 %) were detected on nephrographic phase and excretory phase VNCTs, respectively. The mean size of stones undetected on nephrographic and excretory VNCTs was measured as 1.5 +/- 0.5 mm and 1.6 +/- 0.6 mm, respectively. The mean DLPs of three-phase CTU, nephrographic phase DECT and excretory phase DECT were 1076 +/- 248 mGy . cm, 410 +/- 98 mGy . cm, and 360 +/- 87 mGy . cm, respectively (P < 0.001). CONCLUSIONS: Single-phase DECT has a potential to replace three phase CTU for detecting tumours with a lower radiation dose. KEY POINTS: * Single phase DECT with virtual NCT may replace three-phase CTU for detecting tumours. * Virtual NCT cannot replace NCT for detecting small urinary stones. * Single-phase DECT may reduce the radiation dose by 62-67 % compared to three-phase CTU. * Nephrographic phase DECT is superior to excretory phase DECT for assessing haematuria. PMID- 26883331 TI - Prognostic value of total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with uterine carcinosarcoma. AB - OBJECTIVES: To investigate the relationship between functional tumour parameters measured during preoperative 18F-FDG PET/CT and clinical outcomes in patients with uterine carcinosarcoma. METHODS: For patients with pathologically proven uterine carcinosarcoma, we determined the maximal and average standardized uptake values, cumulative total lesion glycolysis (TLG) and sum of all metabolic tumour volumes (MTVs). Their predictive value for recurrence and the effects of pretreatment functional tumour activity on patient survival were compared. RESULTS: Clinicopathological data from 28 eligible patients were reviewed. The median duration of progression-free survival was 18.6 months (range 6.1-84.5 months), and 10 (35.7 %) patients experienced recurrences. Univariate analyses showed significant associations between recurrence and tumour size, lymph node metastasis, high TLG and MTV values, and ovarian invasion. Multivariate analysis identified high TLG value as an independent risk factor for recurrence (p = 0.048, hazard ratio 115.261, 95 % confidence interval 1.041-12,765.483). Kaplan Meier survival curves showed that progression-free survival significantly differed in groups categorized according to TLG (p = 0.007, log-rank test). CONCLUSIONS: Preoperative TLG measured with 18F-FDG PET/CT was statistically significantly associated with uterine carcinosarcoma recurrence. Metabolic parameters can provide useful quantitative criteria for disease prognostication in patients with uterine carcinosarcoma before treatment. KEY POINTS: * Preoperative TLG was an independent risk factor for recurrence in uterine carcinosarcoma. * Progression-free survival significantly differed in groups categorized by TLG. * Metabolic parameters can provide useful quantitative criteria for disease prognostication. PMID- 26883332 TI - Preoperative staging of non-small cell lung cancer: prospective comparison of PET/MR and PET/CT. AB - OBJECTIVES: To prospectively compare the accuracies of PET/MR and PET/CT in the preoperative staging of non-small cell lung cancer (NSCLC). METHODS: Institutional review board approval and patients' informed consents were obtained. 45 patients with proven or radiologically suspected lung cancer which appeared to be resectable on CT were enrolled. PET/MR was performed for the preoperative staging of NSCLC followed by PET/CT without contrast enhancement on the same day. Dedicated MR images including diffusion weighted images were obtained. Readers assessed PET/MR and PET/CT with contrast-enhanced CT. Accuracies of PET/MR and PET/CT for NSCLC staging were compared. RESULTS: Primary tumour stages (n = 40) were correctly diagnosed in 32 patients (80.0 %) on PET/MR and in 32 patients (80.0 %) on PET/CT (P = 1.0). Node stages (n = 42) were correctly determined in 24 patients (57.1 %) on PET/MR and in 22 patients (52.4 %) on PET/CT (P = 0.683). Metastatic lesions in the brain, bone, liver, and pleura were detected in 6 patients (13.3 %). PET/MR missed one patient with pleural metastasis while PET/CT missed one patient with solitary brain metastasis and two patients with pleural metastases (P = 0.480). CONCLUSIONS: This study demonstrated that PET/MR in combination with contrast-enhanced CT was comparable to PET/CT in the preoperative staging of NSCLC while reducing radiation exposure. KEY POINTS: * PET/MR can be comparable to PET/CT for preoperative NSCLC staging. * PET/MR and PET/CT show excellent correlation in measuring SUVmax of primary lesions. * Using PET/MR, estimated radiation dose can decrease by 31.1 % compared with PET/CT. PMID- 26883333 TI - Added value of amide proton transfer imaging to conventional and perfusion MR imaging for evaluating the treatment response of newly diagnosed glioblastoma. AB - OBJECTIVES: To determine the added value of amide proton transfer (APT) imaging to conventional and perfusion MRI for differentiating tumour progression (TP) from the treatment-related effect (TE) in patients with post-treatment glioblastomas. METHODS: Sixty-five consecutive patients with enlarging contrast enhancing lesions following concurrent chemoradiotherapy were assessed using contrast-enhanced T1-weighted MRI (CE-T1WI), 90th percentile histogram parameters of normalized cerebral blood volume (nCBV90) and APT asymmetry value (APT90). Diagnostic performance was determined using the area under the receiver operating characteristic curve (AUC) and cross validations. RESULTS: There were statistically significant differences in the mean APT90 between the TP and the TE groups (3.87-4.01 % vs. 1.38-1.41 %; P < .001). Compared with CE-T1WI alone, the addition of APT90 to CE-T1WI significantly improved cross-validated AUC from 0.58 0.74 to 0.89-0.91 for differentiating TP from TE. The combination of CE-T1WI, nCBV90 and APT90 resulted in greater diagnostic accuracy for differentiating TP from TE than the combination of CE-T1WI and nCBV90 (cross-validated AUC, 0.95 0.97 vs. 0.84-0.91). The inter-reader agreement between the expert and trainee was excellent for the measurements of APT90 (intraclass correlation coefficient, 0.94). CONCLUSION: Adding APT imaging to conventional and perfusion MRI improves the diagnostic performance for differentiating TP from TE. KEY POINTS: * APT imaging could provide a reliable distinction between TP and TE * Adding APT imaging to CE-T1WI improved the diagnostic accuracy versus CE-T1WI alone * Multimodal imaging using CE-T1WI, perfusion and APT imaging led to accurate diagnosis * The inter-reader agreement of APT histogram parameters was excellent. PMID- 26883335 TI - Acute coronary syndrome: evaluation of detection capability using non electrocardiogram-gated parenchymal phase CT imaging. AB - PURPOSE: To evaluate the capability to detect acute coronary syndrome (ACS) by using non-electrocardiogram-gated parenchymal phase CT imaging. MATERIALS AND METHODS: Of 962 consecutive patients who underwent emergent coronary angiography for suspected ACS, 32 with ACS who underwent CT <=24 h before angiography and 15 without ACS who underwent CT <=24 h before or after angiography were included. Parenchymal phase was acquired at 100-s scan delay. The presence of a myocardial perfusion defect (MPD) on the left ventricle (a decrease of >20 HU) and its capability to detect ACS were evaluated. Results were compared with laboratory findings. RESULTS: MPD was detected in 29 of 32 ACSs. The sensitivity, specificity, and positive and negative predictive values were 91 % (29/32), 93 % (14/15), 97 % (29/30), and 82 % (14/17), respectively. The sensitivities of ST- and non-ST-elevation ACSs were 89 % (16/18) and 93 % (13/14), respectively, without significant difference (P > 0.99). Of the CT-detectable ACS, non-ST elevation on the electrocardiogram and a normal creatine kinase-myocardial band were observed in 41 % (12/29) and 24 % (7/29), respectively. CONCLUSION: ACS is highly detectable even using conventional parenchymal phase CT imaging. Therefore, even when CT is non-gating, radiologists should carefully evaluate the heart to avoid overlooking ACS. PMID- 26883334 TI - Risk Stratification in Multiple Myeloma. AB - There are many prognostic variables in multiple myeloma and the difficulty is in deciding which is truly significant. The widely used International Staging System (ISS) does not incorporate genetics, age, and other important variables in its risk stratification. Although it has its own limitations, the recently published Revised International Staging System (R-ISS) that was built upon the framework of ISS, is a more comprehensive and predictive tool for multiple myeloma patients and should be henceforth utilised. We will review the current prognostic variables and their significance in this paper. PMID- 26883336 TI - Ideology versus evidence: Investigating the claim that the literature on e cigarettes is undermined by material conflict of interest. AB - A review of the health effects of e-cigarettes (EC) by Pisinger and Dossing concluded that any reassuring the evidence on the contents of e-cigarettes cannot be trusted because 'A substantial number of studies were funded or otherwise supported by manufacturers of ECs' and the relevant literature is influenced by 'severe conflicts of interest' (A). The review also asserts that 'Conflict of interest seems to influence the conclusions of these papers' (BC). These claims have been embraced and magnified by EC opponents. The Pisinger and Dossing review included 76 studies and considered 26 (34%) to be 'funded or otherwise supported' by the industry. As the review identifies the 'conflicted' studies, such a claim can be checked. In summary, only 10 (13%) of articles covered by the review were sponsored by the industry and only 5 are published studies. Claim 'A' is misleading. Regarding claim 'B', it appears to have been conceived independent of any empirical support. Recently, anti-EC activists and media started to use conflict of interest accusations to disparage the validity of empirical evidence showing that vaping is much safer than smoking. Evidence needs to be considered on its merits rather than from the perspective of preconceived ideological positions. PMID- 26883337 TI - Occurrence of fibronectin-fibrin complexes in plasma of patients with multimorbidity due to the inflamm-aging phenomenon. AB - BACKGROUND: Multimorbidity is the co-occurrence of chronic diseases associated with low-grade chronic inflammation of connective tissue. AIM OF STUDY: Frequency of occurrence and relative amounts of fibronectin (FN) complexes with fibrin (FN fibrin) and FN monomer were analyzed in 130 plasma samples of 18 to 94-year-old multimorbid patients in relation to concentrations of FN and extra domain A (EDA) FN, and C-reactive protein (CRP) as well as to age, number of coexisting chronic diseases and presence of specified diseases. RESULTS: Immunoblotting revealed, besides FN dimer, the presence of FN monomer, and 750-, 1000-, and 1300-kDa FN fibrin complexes in the multimorbid plasmas. The FN-fibrin complexes appeared more frequently and in higher relative amounts, but FN monomer less frequently and in a lower relative amount in the groups of elderly multimorbid patients, with a higher number of coexisting diseases and with dominance of cardiovascular diseases and osteoarthrosis, and with CRP concentration of 3-5mg/l. In contrast, the normal plasma contained only the FN-fibrin complex of 750 kDa in a lower relative amount, but with an increasing amount with normal aging. Moreover, FN concentration increased and EDA-FN decreased with the number of co-existing diseases and aging of patients, although both concentration values were lower than in the age-matched normal groups. FN concentration was the lowest in the exacerbation of a chronic disease and EDA-FN in the stable chronic disease groups. CONCLUSION: The alterations in plasma FN molecular status were associated with micro-inflammation and micro-coagulation, as well as multimorbidity of subjects and their physiological aging. PMID- 26883338 TI - Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review. AB - INTRODUCTION: Immunosenescence is the age-related deterioration of immunocompetence which is reflected in a poorer response to new antigens. This process is characterized by decreases in naive T cells and increases in memory T cells. The highly prevalent beta-herpesvirus cytomegalovirus (CMV) is thought to enhance T-cell immunosenescence. The aim of this study was to perform a systematic review on the current evidence regarding the relation between CMV infection and immunosenescence in Western people aged fifty years and older. METHODS: Studies that investigated the relation between CMV infection and immune parameters in Western people aged 50 years and older were eligible for inclusion. No restrictions were placed on study type. This article focuses on the relation between CMV infections as measured by serology and T cell subsets. A narrative approach to data synthesis was applied. RESULTS: In the majority of included studies higher levels of Effector Memory (EM) and TEMRA (Effector Memory T cells re-expressing CD45RA) cells were found in the CD4+ and the CD8+ T cell pools in CMV-seropositive elderly compared to CMV-seronegative elderly. No clear evidence was found for lower levels of naive T cells in CMV-seropositive elderly compared to CMV-seronegative elderly. The total CD8+ T cell pool appeared to be larger in CMV-seropositive elderly in three out of four studies, while the total CD4+ T cell pool appeared to be smaller in CMV-seropositive elderly in two out of four studies. DISCUSSION: CMV seems to enhance immunosenescence based on the high levels of the highly differentiated EM and TEMRA cells in the CD8+ and CD4+ T cell pools. The relation of the shifts within the T cell compartments in CMV seropositive elderly in relation to susceptibility to infectious diseases remains to be investigated. PMID- 26883339 TI - Gene expression differences in relation to age and social environment in queen and worker bumble bees. AB - Eusocial insects provide special insights into the genetic pathways influencing aging because of their long-lived queens and flexible aging schedules. Using qRT PCR in the primitively eusocial bumble bee Bombus terrestris (Linnaeus), we investigated expression levels of four candidate genes associated with taxonomically widespread age-related pathways (coenzyme Q biosynthesis protein 7, COQ7; DNA methyltransferase 3, Dnmt3; foraging, for; and vitellogenin, vg). In Experiment 1, we tested how expression changes with queen relative age and productivity. We found a significant age-related increase in COQ7 expression in queen ovary. In brain, all four genes showed higher expression with increasing female (queen plus worker) production, with this relationship strengthening as queen age increased, suggesting a link with the positive association of fecundity and longevity found in eusocial insect queens. In Experiment 2, we tested effects of relative age and social environment (worker removal) in foundress queens and effects of age and reproductive status in workers. In this experiment, workerless queens showed significantly higher for expression in brain, as predicted if downregulation of for is associated with the cessation of foraging by foundress queens following worker emergence. Workers showed a significant age-related increase in Dnmt3 expression in fat body, suggesting a novel association between aging and methylation in B. terrestris. Ovary activation was associated with significantly higher vg expression in fat body and, in younger workers, in brain, consistent with vitellogenin's ancestral role in regulating egg production. Overall, our findings reveal a mixture of novel and conserved features in age related genetic pathways under primitive eusociality. PMID- 26883340 TI - Multiple sclerosis patients' experiences in relation to the impact of the kinect virtual home-exercise programme: a qualitative study. AB - BACKGROUND: Neurorehabilitation programs are among the most popular therapies aimed at reducing the disabilities that result from multiple sclerosis. Video games have recently gained importance in the rehabilitation of patients with motor neurological dysfunctions. Currently, the studies describing the perspective of patients with multiple sclerosis who have participated in rehabilitation programmes via home-based video games are almost inexistent. AIM: The aim of this paper was to explore the experiences of multiple sclerosis patients who performed a virtual home-exercise programme using Kinect. DESIGN: A qualitative research enquiry was conducted as part of a study that examined postural control and balance after a 10-week Kinect home-exercise programme in adults with multiple sclerosis. SETTING: Patients were recruited from a Neurology Unit of a University Hospital. POPULATION: The inclusion criteria were: subjects aged between 20 and 60 years, diagnosed with multiple sclerosis for over 2 years based on the McDonald Criteria; with an EDSS score ranging from 3 to 5. METHODS: Purposeful sampling method was implemented. The data collection consisted of unstructured interviews, using open questions, and thematic analysis was conducted. Guidelines for conducting qualitative studies established by the Consolidated Criteria for Reporting Qualitative Research were followed. RESULTS: Twenty-four patients with a mean age of 36.69 were included. Four main themes emerged from the data: 1) regaining previous capacity and abilities. The patients described how, after the treatment with Kinect they felt more independent; 2) sharing the disease. The patients sharing the experience of living with MS with their family, thanks to the use of Kinect; 3) adapting to the new treatment. This refers to how the use of the videogame console incorporated novelties to their rehabilitation programme; and 4) comparing oneself. This refers to the appearance of factors that motivate the patient during KVHEP. CONCLUSIONS: The patients' experiences gathered in this study highlight perceptions of unexpected improvement, an eagerness to improve, and the positive opportunity of sharing treatment with their social entourage thanks to the games. CLINICAL REHABILITATION IMPACT: These results can be applied to future research using video consoles, by individualizing and adapting the games to the patient's abilities, and by developing a new field in rehabilitation. PMID- 26883341 TI - Effects of a "test in-train out" walking program versus supervised standard rehabilitation in chronic stroke patients: a feasibility and pilot randomized study. AB - BACKGROUND: The loss of normal ambulatory function after stroke, besides causing disability, leads to progressive deconditioning and exposes patients to increased risk of cardiovascular diseases and recurrent stroke. Conventional rehabilitation is mainly limited to the subacute period after stroke. Effective, safe and sustainable interventions for patients and healthcare system, including the long term, should be identified. AIM: To verify the feasibility, safety and preliminary efficacy of an original home-based rehabilitation model compared to a standard supervised program in chronic hemiplegic stroke survivors. DESIGN: Pilot, two-arm, parallel group, randomized, controlled clinical trial. SETTING: Community-dwelling poststroke patient/Hospital. POPULATION: Twelve chronic hemiplegic stroke patients (age=66.5+/-11.9 years, males, N.=9). METHODS: Participants were randomly assigned for a 10-week period to a structured home based exercise program (N.=6) and a standard supervised group-setting program (N.=6). The feasibility outcomes included adherence to interventions, retention rate and safety. Satisfaction was also evaluated by the Client Satisfaction Questionnaire. Efficacy was assessed by the 6-minute walk test, Timed Up and Go and Stair Climb tests. The impact on Quality-of-life was estimated using the physical activity domain of the Short Form-36 questionnaire. Operators' time consuming was also calculated. RESULTS: Adherence was 91% in the home-based exercise group and 92% in the standard supervised group. The retention rate was 100%, with no adverse events reported and high satisfaction scores for both interventions. 6-minute walk test and physical activity domain significantly increased in both groups (P=0.03). Timed Up and Go improved in both groups, significantly for the home-based exercise group (P=0.03) while Stair Climb remained stable. Time required to operators to implement the home-based exercise program was 15 hours vs. 30 hours for the standard supervised one. CONCLUSIONS: In a sample of hemiplegic chronic stroke patients, a structured home-based exercise program was feasible, safe and capable of inducing improvements in functional capacity and Quality-of-life comparable to a conventional supervised rehabilitation program A future larger randomized controlled trial will be needed to confirm such results. CLINICAL REHABILITATION IMPACT: With the limitation of a small sample size, the study suggested that a home-based program for chronic stroke might be an effective alternative to traditional supervised programs with the peculiarity of being sustainable for patients and healthcare system. PMID- 26883342 TI - Electrochemically induced sol-gel deposition of ZnO films on Pt-nanoparticle modified FTO surfaces for enhanced photoelectrocatalytic energy conversion. AB - The low conductivity of transparent conductive oxides such as fluorine-doped tin oxides (FTO) has a high impact on the electrochemically induced deposition of semiconductor films for photoelectrocatalytic investigations. Furthermore, the often high recombination rate of photogenerated electron-hole pairs influences the photoelectrochemical performance of semiconductor films. In order to improve the semiconductor deposition process as well as to decrease electron-hole pair recombination, we propose modification of FTO by electrochemically induced deposition of Pt nanoparticles. The deposited Pt nanoparticles improve on the one hand the conductivity of the FTO and on the other hand they create nuclei at which the sol-gel semiconductor deposition starts. We use ZnO as a well characterised material to evaluate the effect of the influencing parameters during electrochemically induced sol-gel deposition with respect to the incident photon-to-current efficiency (IPCE) derived from wavelength dependent photocurrent spectroscopy. Using optimised deposition parameters a substantially decreased recombination rate of photogenerated charge carriers is demonstrated, if Pt-nanoparticles are first deposited on the FTO surface. By improving the diffusion of photogenerated electrons to the Pt nanoparticles and hence to the back contact the photoelectrochemical performance of the deposited ZnO films is substantially increased. PMID- 26883343 TI - Commentary to: Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene. PMID- 26883344 TI - Ursolic acid-loaded chitosan nanoparticles induce potent anti-angiogenesis in tumor. AB - Angiogenesis provides necessary nutrients and oxygen for tumor growth and metastasis; thus, every stage of angiogenesis process is the potential target for cancer therapies. Ursolic acid (UA) is reported to decrease tumor burden through anti-angiogenesis pathway, but its poor water solubility greatly limits its efficiency and clinical application. Here, a simple method for preparing UA loaded chitosan nanoparticles (CH-UA-NPs) with anti-angiogenesis and anti-tumor activity was demonstrated. In vitro, CH-UA-NPs could significantly inhibit the proliferation, migration, and tube formation of human umbilical vascular endothelial cells (HUVECs). After uptake by HUVECs, CH-UA-NPs were mainly localized in lysosomes and mitochondria, but not nuclei. CH-UA-NPs induced the destruction of lysosome membrane integrity, collapse of mitochondrial membrane potential, and reorganization of cell cytoskeleton. All these changes led to the apoptosis or necrosis in HUVECs. In vivo, CH-UA-NPs could inhibit the angiogenesis in chicken chorioallantoic membrane (CAM) model and H22 xenograft model. Notably, comparing with free UA, such synthesized CH-UA-NPs could save about tenfold of UA doses, implying that this could significantly decrease the side effects induced by high doses of UA in biological organism. Our data showed that CH-UA-NPs and this nanoparticle-based drug delivery system could be as a potential drug candidate for anti-angiogenesis treatment. PMID- 26883345 TI - Diammonium phosphate stimulates transcription of L-lactate dehydrogenase leading to increased L-lactate production in the thermotolerant Bacillus coagulans strain. AB - Exploration of cost-effective fermentation substrates for efficient lactate production is an important economic objective. Although some organic nitrogen sources are also cheaper, inorganic nitrogen salts for lactate fermentation have additional advantages in facilitating downstream procedures and significantly improving the commercial competitiveness of lactate production. In this study, we first established an application of diammonium phosphate to replace yeast extract with a reduced 90 % nitrogen cost for a thermotolerant Bacillus coagulans strain. In vivo enzymatic and transcriptional analyses demonstrated that diammonium phosphate stimulates the gene expression of L-lactate dehydrogenase, thus providing higher specific enzyme activity in vivo and increasing L-lactic acid production. This new information provides a foundation for establishing a cost effective process for polymer-grade L-lactic acid production in an industrial setting. PMID- 26883346 TI - Improving monoterpene geraniol production through geranyl diphosphate synthesis regulation in Saccharomyces cerevisiae. AB - Monoterpenes have wide applications in the food, cosmetics, and medicine industries and have recently received increased attention as advanced biofuels. However, compared with sesquiterpenes, monoterpene production is still lagging in Saccharomyces cerevisiae. In this study, geraniol, a valuable acyclic monoterpene alcohol, was synthesized in S. cerevisiae. We evaluated three geraniol synthases in S. cerevisiae, and the geraniol synthase Valeriana officinalis (tVoGES), which lacked a plastid-targeting peptide, yielded the highest geraniol production. To improve geraniol production, synthesis of the precursor geranyl diphosphate (GPP) was regulated by comparing three specific GPP synthase genes derived from different plants and the endogenous farnesyl diphosphate synthase gene variants ERG20 (G) (ERG20 (K197G) ) and ERG20 (WW) (ERG20 (F96W-N127W) ), and controlling endogenous ERG20 expression, coupled with increasing the expression of the mevalonate pathway by co-overexpressing IDI1, tHMG1, and UPC2-1. The results showed that overexpressing ERG20 (WW) and strengthening the mevalonate pathway significantly improved geraniol production, while expressing heterologous GPP synthase genes or down-regulating endogenous ERG20 expression did not show positive effect. In addition, we constructed an Erg20p(F96W-N127W)-tVoGES fusion protein, and geraniol production reached 66.2 mg/L after optimizing the amino acid linker and the order of the proteins. The best strain yielded 293 mg/L geraniol in a fed-batch cultivation, a sevenfold improvement over the highest titer previously reported in an engineered S. cerevisiae strain. Finally, we showed that the toxicity of geraniol limited its production. The platform developed here can be readily used to synthesize other monoterpenes. PMID- 26883347 TI - Cyanobacterial chassis engineering for enhancing production of biofuels and chemicals. AB - To reduce dependence on fossil fuels and curb greenhouse effect, cyanobacteria have emerged as an important chassis candidate for producing biofuels and chemicals due to their capability to directly utilize sunlight and CO2 as the sole energy and carbon sources, respectively. Recent progresses in developing and applying various synthetic biology tools have led to the successful constructions of novel pathways of several dozen green fuels and chemicals utilizing cyanobacterial chassis. Meanwhile, it is increasingly recognized that in order to enhance productivity of the synthetic cyanobacterial systems, optimizing and engineering more robust and high-efficient cyanobacterial chassis should not be omitted. In recent years, numerous research studies have been conducted to enhance production of green fuels and chemicals through cyanobacterial chassis modifications involving photosynthesis, CO2 uptake and fixation, products exporting, tolerance, and cellular regulation. In this article, we critically reviewed recent progresses and universal strategies in cyanobacterial chassis engineering to make it more robust and effective for bio-chemicals production. PMID- 26883348 TI - Screening of bacteria for self-healing of concrete cracks and optimization of the microbial calcium precipitation process. AB - A novel high-throughput strategy was developed to determine the calcium precipitation activity (CPA) of mineralization bacteria used for self-healing of concrete cracks. A bacterial strain designated as H4 with the highest CPA of 94.8 % was screened and identified as a Bacillus species based on 16S rDNA sequence and phylogenetic tree analysis. Furthermore, the effects of certain influential factors on the microbial calcium precipitation process of H4 were evaluated. The results showed that lactate and nitrate are the best carbon and nitrogen sources, with optimal concentrations of approximately 25 and 18 mM, respectively. The H4 strain is able to maintain a high CPA in the pH range of 9.5-11.0, and a suitable initial spore concentration is 4.0 * 10(7) spores/ml. Moreover, an ambient Ca(2+) concentration greater than 60 mM resulted in a serious adverse impact not only on the CPA but also on the growth of H4, suggesting that the maintenance of the Ca(2+) concentration at a low level is necessary for microbial self-healing of concrete cracks. PMID- 26883350 TI - Focused ultrasound to transiently disrupt the blood brain barrier. PMID- 26883349 TI - Effect of cooperation of chaperones and gene dosage on the expression of porcine PGLYRP-1 in Pichia pastoris. AB - Mammalian peptidoglycan recognition proteins (PGLYRPs) are highly conserved pattern-recognition molecules of the innate immune system with considerable bactericidal activity, which manifest their potential values for the application to food and pharmaceutical industry. However, the effective expression of porcine PGLYRP-1 in Pichia pastoris has not been reported so far. In this study, expression in P. pastoris was explored as an efficient way to produce functional porcine PGLYRP-1. Cooperation of chaperones co-expression and gene dosage (including protein disulfide isomerase (PDI)/binding protein (BiP) and pglyrp-1) were used to enhance functional expression of antimicrobial protein in P. pastoris. Overexpression of PDI was certainly able to increase secretion level of PGLYRP-1 protein because the increase in secreted PGLYRP-1 secretion was correlated with the copy numbers of PDI in high copy pglyrp-1 clones. However, co expression of BiP was proved to be detrimental to PGLYRP-1 secretion. In addition, we also found that excessive expression of PDI and/or BiP could decrease the mRNA expression of pglyrp-1 gene. This showed that PDI and BiP as the target genes of unfolded protein response (UPR) might regulate the transcription of the target protein. These data demonstrated for the first time that the combination of chaperones and gene dosages could improve the yield of PGLYRP-1, which could facilitate the application to food and pharmaceutical industry. PMID- 26883351 TI - Pupil-sparing third nerve palsies and hemiataxia: Claude's and reverse Claude's syndrome. AB - We report two patients with midbrain infarction with pupil-sparing third nerve palsies and hemiataxia: one with contralateral ataxia (Claude's syndrome) and one with ipsilateral ataxia (which we refer to as reverse Claude's syndrome). We highlight the importance of a thorough neurologic evaluation with partial oculomotor palsies and describe, to our knowledge, the fourth account in the literature of a pupil-sparing third nerve palsy with ipsilateral cerebellar ataxia. PMID- 26883352 TI - Endocytosis and transcytosis of gliadin peptides. AB - BACKGROUND: Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Some gliadin peptides are not digested by intestinal proteases and can have different biological effects. Gliadin peptides can induce innate and adaptive T cell mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptides 31-43 and 31-55) is the cytokine interleukin-15 (IL-15). Other peptides such as the 33 mer containing the P57-68 sequence, after tissue transglutaminase deamidation, are well presented to T cell in the intestine and can induce an adaptive immune response. FINDINGS: In this paper, we review the recent studies on the digestion of gliadin and the peptides released by the digestion process. We will also discuss the mechanisms responsible for the internalization and transcytosis of indigested gliadin peptides in the intestinal epithelium. CONCLUSIONS: Gliadin is not completely digested by the intestinal proteases producing bioactive peptides that have different biological effects. These peptides are internalized in the cells by an active process of endocytosis and can traverse the intestinal mucosa with different kinetics and immunological effects. In vivo findings will also be discussed. PMID- 26883353 TI - Diverse roles of endoplasmic reticulum stress sensors in bacterial infection. AB - Bacterial infection often leads to cellular damage, primarily marked by loss of cellular integrity and cell death. However, in recent years, it is being increasingly recognized that, in individual cells, there are graded responses collectively termed cell-autonomous defense mechanisms that induce cellular processes designed to limit cell damage, enable repair, and eliminate bacteria. Many of these responses are triggered not by detection of a particular bacterial effector or ligand but rather by their effects on key cellular processes and changes in homeostasis induced by microbial effectors when recognized. These in turn lead to a decrease in essential cellular functions such as protein translation or mitochondrial respiration and the induction of innate immune responses that may be specific to the cellular deficit induced. These processes are often associated with specific cell compartments, e.g., the endoplasmic reticulum (ER). Under non-infection conditions, these systems are generally involved in sensing cellular stress and in inducing and orchestrating the subsequent cellular response. Thus, perturbations of ER homeostasis result in accumulation of unfolded proteins which are detected by ER stress sensors in order to restore the normal condition. The ER is also important during bacterial infection, and bacterial effectors that activate the ER stress sensors have been discovered. Increasing evidence now indicate that bacteria have evolved strategies to differentially activate different arms of ER stress sensors resulting in specific host cell response. In this review, we will describe the mechanisms used by bacteria to activate the ER stress sensors and discuss their role during infection. PMID- 26883354 TI - Fructose malabsorption. AB - Incomplete intestinal absorption of fructose might lead to abdominal complaints such as pain, flatulence and diarrhoea. Whether defect fructose transporters such as GLUT5 or GLUT2 are involved in the pathogenesis of fructose malabsorption is a matter of debate. The hydrogen production by colonic bacteria is used for diagnosis with the hydrogen breath test. However, the appropriate fructose test dose for correct diagnosis is unclear. Subjects with fructose malabsorption show increased breath hydrogen levels and abdominal symptoms after fructose administration but do not report any symptoms when fructose is given together with glucose. This beneficial effect of glucose, however, cannot be explained yet but might be used for clinical care of these subjects. PMID- 26883355 TI - Underlying molecular and cellular mechanisms in childhood irritable bowel syndrome. AB - Irritable bowel syndrome (IBS) affects a large number of children throughout the world. The symptom expression of IBS is heterogeneous, and several factors which may be interrelated within the IBS biopsychosocial model play a role. These factors include visceral hyperalgesia, intestinal permeability, gut microbiota, psychosocial distress, gut inflammation, bile acids, food intolerance, colonic bacterial fermentation, and genetics. The molecular and cellular mechanisms of these factors are being actively investigated. In this mini-review, we present updates of these mechanisms and, where possible, relate the findings to childhood IBS. Mechanistic elucidation may lead to the identification of biomarkers as well as personalized childhood IBS therapies. PMID- 26883356 TI - Comparison of frequency doubling and flicker defined form perimetry in early glaucoma. AB - PURPOSE: To compare perimetric data based on the second-generation frequency doubling technology (FDT) and on flicker defined form (FDF) stimulation in early glaucoma patients. METHODS: Seventy-two experienced glaucoma patients and 50 healthy subjects of the Erlangen Glaucoma Registry participated in the study. The definition of glaucoma was solely based on optic disc appearance. All patients underwent FDF perimetry (HEP), FDT perimetry (Matrix), standard automated perimetry (SAP, Octopus), and peripapillar measurements of the RNFL thickness (Spectralis OCT). Exclusion criteria were: mean defect (MD) in SAP > 6 dB, eye diseases other than glaucoma, or non-reliable FDF or FDT measurements. Statistical analyses included comparison of the standard indices and correlations between methods. Venn-diagrams show the number of patients with abnormal results in HEP, Matrix, SAP, and mean RNFL thickness. RESULTS: Mean defect data from FDT and FDF perimetry were strongly correlated (R = -0.85, P <0.001). In this cohort of early glaucoma patients, the MD values were 6.1 +/- 5.0 dB (FDF) and 4.5 +/- 4.1 dB (FDT). Sensitivity in this patient group was 65 % for FDF-MD, 60 % for FDT MD, and 60 % for RNFL-thickness, all at a specificity of 95 %. The correlation analysis between local RNFL thickness and corresponding visual defects revealed significant Spearman correlation coefficients for the arcuate bundles of the visual field (FDF-inferior: R = -0.65, FDF-superior: R = -0.74, FDT-inferior: R = -0.55, FDT-superior: R = -0.72). CONCLUSION: FDF and FDT stimulations can be used to detect patients with early glaucoma. Combined consideration of RNFL thickness and results from one of these perimetric tests can increase the total number of detected patients. PMID- 26883358 TI - Muscleblind-like 1 suppresses breast cancer metastatic colonization and stabilizes metastasis suppressor transcripts. AB - Post-transcriptional deregulation is a defining feature of metastatic cancer. While many microRNAs have been implicated as regulators of metastatic progression, less is known about the roles and mechanisms of RNA-binding proteins in this process. We identified muscleblind-like 1 (MBNL1), a gene implicated in myotonic dystrophy, as a robust suppressor of multiorgan breast cancer metastasis. MBNL1 binds the 3' untranslated regions (UTRs) of DBNL (drebrin-like protein) and TACC1 (transforming acidic coiled-coil containing protein 1)-two genes that we implicate as metastasis suppressors. By enhancing the stability of these genes' transcripts, MBNL1 suppresses cell invasiveness. Consistent with these findings, elevated MBNL1 expression in human breast tumors is associated with reduced metastatic relapse likelihood. Our findings delineate a post transcriptional network that governs breast cancer metastasis through RNA-binding protein-mediated transcript stabilization. PMID- 26883359 TI - Atg7 cooperates with Pten loss to drive prostate cancer tumor growth. AB - Understanding new therapeutic paradigms for both castrate-sensitive and more aggressive castrate-resistant prostate cancer is essential to improve clinical outcomes. As a critically important cellular process, autophagy promotes stress tolerance by recycling intracellular components to sustain metabolism important for tumor survival. To assess the importance of autophagy in prostate cancer, we generated a new autochthonous genetically engineered mouse model (GEMM) with inducible prostate-specific deficiency in the Pten tumor suppressor and autophagy related-7 (Atg7) genes. Atg7 deficiency produced an autophagy-deficient phenotype and delayed Pten-deficient prostate tumor progression in both castrate-naive and castrate-resistant cancers. Atg7-deficient tumors display evidence of endoplasmic reticulum (ER) stress, suggesting that autophagy may promote prostate tumorigenesis through management of protein homeostasis. Taken together, these data support the importance of autophagy for both castrate-naive and castrate resistant growth in a newly developed GEMM, suggesting a new paradigm and model to study approaches to inhibit autophagy in combination with known and new therapies for advanced prostate cancer. PMID- 26883360 TI - Mutation of cancer driver MLL2 results in transcription stress and genome instability. AB - Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear. Here, we present evidence that MLL2 mutation results in genome instability. Mouse cells in which MLL2 gene deletion can be induced display elevated levels of sister chromatid exchange, gross chromosomal aberrations, 53BP1 foci, and micronuclei. Human MLL2 knockout cells are characterized by genome instability as well. Interestingly, MLL2 interacts with RNA polymerase II (RNAPII) and RECQL5, and, although MLL2 mutated cells have normal overall H3K4me levels in genes, nucleosomes in the immediate vicinity of RNAPII are hypomethylated. Importantly, MLL2 mutated cells display signs of substantial transcription stress, and the most affected genes overlap with early replicating fragile sites, show elevated levels of gammaH2AX, and suffer frequent mutation. The requirement for MLL2 in the maintenance of genome stability in genes helps explain its widespread role in cancer and points to transcription stress as a strong driver in tumorigenesis. PMID- 26883361 TI - Initiation of stem cell differentiation involves cell cycle-dependent regulation of developmental genes by Cyclin D. AB - Coordination of differentiation and cell cycle progression represents an essential process for embryonic development and adult tissue homeostasis. These mechanisms ultimately determine the quantities of specific cell types that are generated. Despite their importance, the precise molecular interplays between cell cycle machinery and master regulators of cell fate choice remain to be fully uncovered. Here, we demonstrate that cell cycle regulators Cyclin D1-3 control cell fate decisions in human pluripotent stem cells by recruiting transcriptional corepressors and coactivator complexes onto neuroectoderm, mesoderm, and endoderm genes. This activity results in blocking the core transcriptional network necessary for endoderm specification while promoting neuroectoderm factors. The genomic location of Cyclin Ds is determined by their interactions with the transcription factors SP1 and E2Fs, which result in the assembly of cell cycle controlled transcriptional complexes. These results reveal how the cell cycle orchestrates transcriptional networks and epigenetic modifiers to instruct cell fate decisions. PMID- 26883362 TI - A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism. AB - The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic lipid accumulation. MED13 suppressed the expression of genes involved in glucose uptake and metabolism in skeletal muscle by inhibiting the nuclear receptor NURR1 and the MEF2 transcription factor. These findings reveal a fundamental molecular mechanism for the governance of glucose metabolism and the control of hepatic lipid accumulation by skeletal muscle. Intriguingly, MED13 exerts opposing metabolic actions in skeletal muscle and the heart, highlighting the customized, tissue-specific functions of the Mediator complex. PMID- 26883364 TI - Moral equality and success of common-pool water governance in Namibia. AB - In the course of decentralization, pastoral communities in Namibia have had to find new ways to share their most salient resource, water, and the costs involved in providing it. Using data from sixty communities, we examine (1) whether and to what extent different sharing rules emerge, (2) how variations can be explained, (3) how rules are perceived and influence success, and (4) what economic consequences they have. Our results reveal that either all members pay the same (numerical equality) or payment is according to usage (proportional equality). We find that although proportional equality provides more success, the rule can only pertain where the state maintains an active role. Simulations show that where it does not prevail, wealth inequality is likely to grow. These findings have political implications and suggest that, in the context of the widespread decentralization policies, the state should not withdraw if it aims to ensure the success of common-pool resource management and to fight poverty. PMID- 26883363 TI - Targeted cell elimination reveals an auxin-guided biphasic mode of lateral root initiation. AB - To sustain a lifelong ability to initiate organs, plants retain pools of undifferentiated cells with a preserved proliferation capacity. The root pericycle represents a unique tissue with conditional meristematic activity, and its tight control determines initiation of lateral organs. Here we show that the meristematic activity of the pericycle is constrained by the interaction with the adjacent endodermis. Release of these restraints by elimination of endodermal cells by single-cell ablation triggers the pericycle to re-enter the cell cycle. We found that endodermis removal substitutes for the phytohormone auxin-dependent initiation of the pericycle meristematic activity. However, auxin is indispensable to steer the cell division plane orientation of new organ-defining divisions. We propose a dual, spatiotemporally distinct role for auxin during lateral root initiation. In the endodermis, auxin releases constraints arising from cell-to-cell interactions that compromise the pericycle meristematic activity, whereas, in the pericycle, auxin defines the orientation of the cell division plane to initiate lateral roots. PMID- 26883366 TI - German translation and validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA revised (PISQ-IR). AB - INTRODUCTION AND HYPOTHESIS: Condition-specific sexual questionnaires are essential for clinical trials and important patient-reported outcome measures. The aim of the study was to translate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into German and to clinically validate it in a German-speaking population. METHODS: The translated PISQ-IR was linguistically validated in two rounds of cognitive interviews. The final instrument was psychometrically validated in women presenting to urogynecological clinics with pelvic floor dysfunction. For analysis of criterion validity, three related self-reported measures were administered: the Female Sexual Function Index (FSFI), the Kings Health Questionnaire (KHQ), and the 36-Item Short Form Health Survey (SF-36). For external validity, PISQ-IR subscales were compared to the clinical-measures Pelvic Organ Prolapse Quantification system (POP-Q) stage, pelvic floor muscle tone, and Oxford Grading Scale. Descriptive statistics, floor and ceiling effects, internal consistency using Cronbach's alpha coefficient, and Pearson correlations were calculated for all PISQ-IR subscales. RESULTS: The PISQ-IR was completed by 197 women, out of whom 66 (33.5 %) considered themselves not sexually active (NSA) and 131 (66.5 %) as sexually active (SA). Participants' mean age was 57 +/- 12 years; 50 % were diagnosed with symptomatic POP, 74 % with urinary incontinence (UI) and 4 % with anal incontinence (AI). The PISQ-IR subscales were analyzed separately for SA and NSA women with Cronbach's alpha coefficients ranging from 0.64 to 0.94. Moderate to high correlations were observed between PISQ-IR subscales and related quality of life (QoL) scales and corresponding FSFI scales. CONCLUSION: Initial testing of the German PISQ-IR suggests it is an internally consistent and valid tool for use in clinical practice and research. PMID- 26883365 TI - Oxidative stress and DNA damage in patients with migraine. AB - BACKGROUND: Oxidative stress is implicated in the pathogenesis of migraine, but no published studies have examined both oxidative stress levels and oxidative DNA damage on the same patient group. METHODS: In this study, total oxidant status (TOS); total antioxidant status (TAS); oxidative stress index (OSI); and 8 hydroxy-2'-deoxyguanosine (8-OHdG), which is an indicator of oxidative DNA damage, were measured in the plasma samples of 50 prophylactic unmediated migraineurs (11 with aura and 39 without aura) and 30 matched healthy volunteers. RESULTS: No significant differences in TAS, TOS, and OSI values were observed between patients and controls. However, plasma 8-OHdG levels were found to be significantly higher in migraine patients than in the control group (p = 0.001); this increase in plasma 8-OHdG levels was more prominent in cases with migraine without aura than with aura (p = 0.001). Our results suggested an evidence of oxidative stress-related DNA damage in migraine. CONCLUSION: DNA damage reflected by plasma 8-OHdG did not studied in migraine before. Therefore, further research on oxidative stress-related DNA damage and the extent of its clinical manifestations in migraine may provide additional data to our current knowledge. PMID- 26883367 TI - Role of diet in fecal incontinence: a systematic review of the literature. AB - INTRODUCTION AND HYPOTHESIS: The objective was to perform a systematic review of the literature to examine original research on the role of diet in fecal incontinence (FI) with a dual focus on dietary differences in FI and dietary treatments for FI. METHODS: We searched the PubMed and Embase databases for any peer-reviewed original research in English on the role of diet in FI. RESULTS: We identified 172 unique citations. After title review and exclusion of articles not reporting original research, 9 publications were included in the final review: 4 focused on dietary differences and 5 focused on dietary treatments for FI. Limited evidence indicates that macro- and micronutrient intake does not differ significantly in those with and without FI. However, certain foods were perceived to improve or exacerbate FI symptoms and these varied and were adjusted as part of self-care practices. A high-fiber diet may reduce incontinence frequency. CONCLUSIONS: Data on the pathogenesis of FI from a dietary perspective are scant. Based on the limited data, dietary differences between those with and without FI provide little insight with the exception of fiber. Further studies are needed to elucidate treatments for FI using fiber and dietary modifications. PMID- 26883357 TI - Genetics and biology of pancreatic ductal adenocarcinoma. AB - With 5-year survival rates remaining constant at 6% and rising incidences associated with an epidemic in obesity and metabolic syndrome, pancreatic ductal adenocarcinoma (PDAC) is on track to become the second most common cause of cancer-related deaths by 2030. The high mortality rate of PDAC stems primarily from the lack of early diagnosis and ineffective treatment for advanced tumors. During the past decade, the comprehensive atlas of genomic alterations, the prominence of specific pathways, the preclinical validation of such emerging targets, sophisticated preclinical model systems, and the molecular classification of PDAC into specific disease subtypes have all converged to illuminate drug discovery programs with clearer clinical path hypotheses. A deeper understanding of cancer cell biology, particularly altered cancer cell metabolism and impaired DNA repair processes, is providing novel therapeutic strategies that show strong preclinical activity. Elucidation of tumor biology principles, most notably a deeper understanding of the complexity of immune regulation in the tumor microenvironment, has provided an exciting framework to reawaken the immune system to attack PDAC cancer cells. While the long road of translation lies ahead, the path to meaningful clinical progress has never been clearer to improve PDAC patient survival. PMID- 26883369 TI - Spot-scanned pancreatic stereotactic body proton therapy: A dosimetric feasibility and robustness study. AB - PURPOSE: We explored the dosimetric potential of spot-scanned stereotactic body proton therapy (SBPT) for pancreatic cancer. METHODS: We compared SBPT to stereotactic body intensity-modulated radiotherapy (SB-IMRT) in 10 patients. We evaluated 3 variables in SBPT planning: (1) 4 and 6 mm spot size; (2) single vs. multi-field optimization (SFO vs. MFO); and (3) optimization target volume (OTV) expansion. Robustness analysis was performed with unidirectional isocenter shifts of +/-3 mm in x, y, and z and +/-3% stopping power uncertainties. RESULTS: SBPT plans had lower V10Gy for the stomach and small and large bowels. Under static robustness, a 5 mm OTV and SFO-6 mm spot size represented the best compromise between target and normal structure. A 4-mm spot-size and 3 mm OTV resulted in significant target underdosing with deformable dose accumulation analysis. CONCLUSIONS: This study provides a critical basis for clinical translation of spot size, optimization technique, and OTV expansion for pancreatic SBPT. PMID- 26883368 TI - Clinical Outcome of Patients with Aortic Stenosis and Coronary Artery Disease Not Treated According to Current Recommendations. AB - We evaluated the clinical outcome of patients with moderate/severe aortic stenosis and significant coronary disease not treated according to guidelines, recommending combined aortic valve replacement (AVR) and coronary artery bypass grafting (CABG). From 2002 to 2010, we assessed death up to 5 years in 650 patients with moderate/severe aortic stenosis and at least one coronary lesion (>50 %): 23 % were treated conservatively (MT), 17 % with percutaneous coronary intervention (PCI), 11 % with AVR, and 49 % with combined CABG and AVR. At a median follow-up of 58 months, overall death decreased over the groups (MT, 68 % vs. PCI, 44 % vs. AVR, 34 % vs. CABG and AVR, 23 %, p < 0.01). Compared to the MT group, Cox regression analysis adjusted for potential confounders showed significantly reduced mortality in the PCI, AVR, and CABG and AVR groups. When combined CABG and AVR is not feasible, PCI or AVR alone still improves significantly long-term survival as compared with MT alone. PMID- 26883370 TI - Awake thoracic surgery versus chemical pleurodesis for intractable secondary spontaneous pneumothorax. AB - PURPOSE: To compare the outcomes and efficacy of awake video-assisted thoracic surgery (VATS) with those of chemical pleurodesis for intractable secondary spontaneous pneumothorax (SSP). METHODS: We analyzed, retrospectively, 60 consecutive patients who underwent awake VATS (n = 22) or chemical pleurodesis (n = 38) for SSP. Using propensity score matching, we identified comparable patient groups (n = 12 each): the awake VATS group and the chemical pleurodesis group. We compared hematologic data on postoperative day 1, postoperative complications including respiratory complications, and the maximum score on the verbal rating scale (VRS) between the groups. Next, we identified comparable patient groups (n = 8 each) for those with controlled air leak after treatment, but not for those with a prolonged air leak. We analyzed data about the day of air leak control, intra-thoracic drainage, and hospital stay to compare awake VATS vs. chemical pleurodesis. RESULTS: After propensity score matching, the rates of recurrent pneumothorax and prolonged air leaks after conservative or surgical treatment were not significantly different. The C-reactive protein level and the VRS score were significantly lower in the awake VATS group. The duration of prolonged air leak, and drainage after treatment were significantly shorter in the awake VATS group. The postoperative hospital stay and the incidence of postoperative complications did not differ between the groups. CONCLUSIONS: We advocate that awake VATS, performed by a skilled thoracic surgeon, is a more feasible surgical option than chemical pleurodesis for patients with intractable SSP. PMID- 26883371 TI - Data-driven Critical Zone science: A new paradigm. AB - This paper uses examples from Australia to argue for a new approach to integrative research in the Earth's near surface environment where the pedosphere, atmosphere, hydrosphere, and biosphere interact, the so-called 'Critical Zone'. In Australia, for around 25years, environmental data layers presented through Geographical Information Systems software have been combined with field-based measurements and observations to produce spatially explicit predictive models for digitally mapping soils and soil properties. The availability of spatially extensive datasets representing different factors of landscape evolution and their exploration with machine learning and rule induction techniques also allow the evaluation of emergent patterns against existing domain knowledge, which in turn can lead to new insights and can facilitate their extrapolation over large areas. Thus the data-driven approach is complementary to the hypothesis-driven scientific inquiry in Critical Zone observatories. PMID- 26883373 TI - Erratum: Cross-modal and modality-specific expectancy effects between pain and disgust. PMID- 26883374 TI - Detection of preperimetric glaucoma using Bruch membrane opening, neural canal and posterior pole asymmetry analysis of optical coherence tomography. AB - We analysed retinal nerve fibre layer (RNFL) defects in eyes with normal circumpapillary RNFL (cpRNFL) thickness using posterior pole asymmetry analysis (PPAA) and investigated the parameters of Bruch membrane opening (BMO) and neural canals using enhanced depth imaging spectral domain optical coherence tomography (EDI-SDOCT). A total of 112 preperimetric glaucomatous eyes of 92 patients were examined to obtain cpRNFL thickness using SD-OCT. Posterior pole asymmetry analysis (PPAA) and central cross-sectional images of the optic nerve head (ONH) were obtained using EDI-SDOCT. Minimal and horizontal distances between the BMO and ONH surfaces (BMOM, BMOH) and the terminal of retinal pigment epithelium (RPE) and ONH surfaces (RPEM, RPEH) were measured. The distribution of the absolute black cells in PPAA was more concentrated in eyes with "U"-shaped neural canals (p < 0.0001). The area under the receiver operating characteristic curve of the ratio of RPEM to RPEH (RPE-R, 0.771 +/- 0.08) was significantly larger than the ratio of BMOM to BMOH (BMO-R, 0.719 +/- 0.009) for PPAA results. A U shaped neural canal, lower ratio of RPEM to RPEH, and lower ratio of BMOM to BMOH were considered early indicators of RNFL defects in preperimetric glaucomatous eyes with normal cpRNFL. PMID- 26883372 TI - Obesity Among Young Adults in Developing Countries: A Systematic Overview. AB - This article discusses the overweight/obesity situation among young adults in developing countries. For this target population, obesity prevalence ranges from 2.3 to 12 %, and overweight is 28.8 %, mostly affecting females. Weight is now increasing during this life stage of transition at a higher rate, 1 kg/year, than in developed countries. Maternal factors and early childhood socioeconomic status are associated with BMI in young adults along with changing environmental and behavioural factors in some low and middle income countries, brought about by demographic and socioeconomic transitions. Young adults with 'normal weight' obesity need identification using other convenient low cost measures (skin folds or waist circumference) along with BMI. Obesity prevention or management interventions were not identified, but clearly needed to help stem the obesity pandemic. Young people generally give little priority to their future health, so such interventions need to be conducted at some optimal age, be innovative, country specific and culturally acceptable. PMID- 26883375 TI - A single generation of domestication heritably alters the expression of hundreds of genes. AB - The genetic underpinnings associated with the earliest stages of plant and animal domestication have remained elusive. Because a genome-wide response to selection can take many generations, the earliest detectable changes associated with domestication may first manifest as heritable changes to global patterns of gene expression. Here, to test this hypothesis, we measured differential gene expression in the offspring of wild and first-generation hatchery steelhead trout (Oncorhynchus mykiss) reared in a common environment. Remarkably, we find that there were 723 genes differentially expressed between the two groups of offspring. Reciprocal crosses reveal that the differentially expressed genes could not be explained by maternal effects or by chance differences in the background levels of gene expression among unrelated families. Gene-enrichment analyses reveal that adaptation to the novel hatchery environment involved responses in wound healing, immunity and metabolism. These findings suggest that the earliest stages of domestication may involve adaptation to highly crowded conditions. PMID- 26883376 TI - Effect of reduced glutathione (GSH) in canine sperm cryopreservation: In vitro and in vivo evaluation. AB - The aim of this study was to compare the in vitro and in vivo efficiency of different concentrations (0, 10 and 20 mM) of reduced glutathione supplemented to the extender for canine semen cryopreservation. Six normospermic dogs were used and each ejaculate was divided in 3 experimental groups, according to GSH concentration (GSH-0, GSH-10 and GSH-20 Groups). After thawing, samples were evaluated by sperm motility by computer-assisted sperm analysis (CASA), flow cytometric evaluation of plasma and acrosome membrane integrity, mitochondrial membrane potential and activity, chromatin susceptibility to acid-induced denaturation, and measurement of spontaneous and induced production of thiobarbituric acid reactive substances (TBARS). In vivo tests were carried out with GSH-0 and GSH-10 groups, for which six bitches were inseminated with semen cryopreserved in extender without GSH or containing 10 mM GSH. Intrauterine insemination was performed by cervical catheterization on the 5th and 6th days after the LH surge, detected by serum progesterone and LH assays. In the CASA evaluation, GSH-20 group had the lowest total and progressive motility and lower percentage of sperm with rapid and slow speed. Groups treated with glutathione showed lower percentage of acrosome damage, but higher percentage of plasma membrane injury. GSH-20 group had higher percentage of sperm with low mitochondrial activity and higher concentration of induced TBARS. Both groups (GSH-0 and GSH-10) had positive pregnancies. In conclusion, 20 mM GSH supplementation to canine cryopreservation extender promoted sperm damage, especially to mitochondrial activity. However, addition of 10 mM GSH resulted in acrosome protection, preserving fertility rate. PMID- 26883377 TI - Detection and genome analysis of a novel (dima)rhabdovirus (Riverside virus) from Ochlerotatus sp. mosquitoes in Central Europe. AB - During an investigation for potential arboviruses present in mosquitoes in Hungary (Central Europe) three highly similar virus strains of a novel rhabdovirus (family Rhabdoviridae) called Riverside virus (RISV, KU248085 KU248087) were detected and genetically characterized from Ochlerotatus sp. mosquito pools collected from 3 geographical locations using viral metagenomic and RT-PCR methods. The ssRNA(-) genome of RISVs follows the general genome layout of rhabdoviruses (3'-N-P-M-G-L-5') with two alternatives, small ORFs in the P and G genes (Px and Gx). The genome of RISVs contains some unusual features such as the large P proteins, the short M proteins with the absence of N-terminal region together with the undetectable "Late budding" motif and the overlap of P and M genes. The unusually long 3' UTRs of the M genes of RISVs probably contain a remnant transcription termination signal which is suggesting the presence of an ancestral gene. The phylogenetic analysis and sequence comparisons show that the closest known relative of RISVs is the recently identified partially sequenced mosquito-borne rhabdovirus, North Creek virus (NOCRV), from Australia. The RISVs and NOCRV form a distinct, basally rooted lineage in the dimarhabdovirus supergroup. The host species range of RISVs is currently unknown, although the presence of these viruses especially in Ochlerotatus sp. mosquitoes which are known to be fierce biting pests of humans and warm-blooded animals and abundant and widespread in Hungary could hold some potential medical and/or veterinary risks. PMID- 26883378 TI - S1 gene-based phylogeny of infectious bronchitis virus: An attempt to harmonize virus classification. AB - Infectious bronchitis virus (IBV) is the causative agent of a highly contagious disease that results in severe economic losses to the global poultry industry. The virus exists in a wide variety of genetically distinct viral types, and both phylogenetic analysis and measures of pairwise similarity among nucleotide or amino acid sequences have been used to classify IBV strains. However, there is currently no consensus on the method by which IBV sequences should be compared, and heterogeneous genetic group designations that are inconsistent with phylogenetic history have been adopted, leading to the confusing coexistence of multiple genotyping schemes. Herein, we propose a simple and repeatable phylogeny based classification system combined with an unambiguous and rationale lineage nomenclature for the assignment of IBV strains. By using complete nucleotide sequences of the S1 gene we determined the phylogenetic structure of IBV, which in turn allowed us to define 6 genotypes that together comprise 32 distinct viral lineages and a number of inter-lineage recombinants. Because of extensive rate variation among IBVs, we suggest that the inference of phylogenetic relationships alone represents a more appropriate criterion for sequence classification than pairwise sequence comparisons. The adoption of an internationally accepted viral nomenclature is crucial for future studies of IBV epidemiology and evolution, and the classification scheme presented here can be updated and revised novel S1 sequences should become available. PMID- 26883379 TI - Antibiotic cross-resistance in the lab and resistance co-occurrence in the clinic: Discrepancies and implications in E.coli. AB - INTRODUCTION: Antibiotic resistance is an important public health issue, and vast resources are invested in researching new ways to fight it. Recent experimental works have shown that resistance to some antibiotics can result in increased susceptibility to others, namely induce cross-sensitivity. This phenomenon could be utilized to increase efficiency of antibiotic treatment strategies that minimize resistance. However, as conditions in experimental settings and in the clinic may differ substantially, the implications of cross-sensitivity for clinical settings are not guaranteed and should be examined. METHODS: In this work we analyzed data of Escherichia coli isolates from patients' blood, sampled in Rabin Medical Center, Israel, to examine co-occurrence of resistance to antibiotics in the clinic. We compared the co-occurrence patterns with cross sensitivity patterns observed in the lab. RESULTS: Our data showed only positively associated occurrence of resistance, even with antibiotics that were shown to induce cross-sensitivity in laboratory conditions. We used a mathematical model to examine the potential effects of cross-sensitivity versus co-occurrence on the spread of drug resistance. CONCLUSIONS: We conclude that resistance frequencies in the clinic can have a substantial effect on the success of treatment strategies, and should be considered alongside experimental evidence of cross-sensitivity. PMID- 26883380 TI - Ultrasound Strain Elastography in Assessment of Muscle Stiffness in Acute Levodopa Challenge Test: A Feasibility Study. AB - To evaluate the feasibility of ultrasound strain elastography in assessing the response of muscle stiffness to the acute levodopa test, we prospectively performed strain elastography on the biceps brachii muscle (BBM) of 18 patients to diagnose Parkinson's disease. BBM and subcutaneous tissue strains (deformations) were produced by external compression with an ultrasound transducer and estimated using 2-D speckle tracking. We used the strain ratio (SR = BBM strain/reference strain) to assess BBM stiffness. The rate of increase in SR [rate = (SR after levodopa-SR before levodopa)/SR before levodopa] was used to assess the muscle stiffness response to levodopa. SR significantly increased after levodopa administration in 11 patients with Parkinson's disease (p = 0.02), whereas it did not in 7 patients with parkinsonian syndrome (from non-Parkinson's causes) (p = 0.14). The area under the receiver operating characteristic curve for the rate of increase in SR in determining Parkinson's disease was 0.96. The rate of increase in SR seems to be feasible in evaluating the effect of levodopa on muscle stiffness in the diagnosis of Parkinson's disease. PMID- 26883381 TI - Molecular characterization and mRNA expression of hypoxia inducible factor-1 and cognate inhibiting factor in Macrobrachium nipponense in response to hypoxia. AB - Hypoxia inducible factors (HIFs) are considered to be the master switches of oxygen-dependent gene expression in mammalian species. Currently, very little is known about the function of this important pathway or the molecular structures of key players in the hypoxia-sensitive Oriental River Prawn Macrobrachium nipponense. In this study, HIFs-1alpha (HIF-1alpha), -1beta (HIF-1beta) and HIF 1 alpha inhibitor (FIH-1) from M. nipponense were cloned. The 4903-bp cDNA of M. nipponense HIF-1alpha (MnHIF-1alpha) encodes a protein of 1088 aa, M. nipponense HIF-1beta (MnHIF-1beta) spans 2042bp encoding 663 aa and the 1163bp M. nipponense FIH-1 (MnFIH-1) specifies a polypeptide of 345 aa. MnHIF-1 and MnFIH-1 homologs exhibit significant sequence similarity and share key functional domains with previously described vertebrate and invertebrate isoforms. Phylogenetic analysis identifies that genetic diversification of HIF-1 and FIH-1 occurred within the invertebrate lineage, indicating functional specialization of the oxygen sensing pathways in this group. Quantitative real-time RT-PCR demonstrated that MnHIF-1 and MnFIH-1 mRNA are expressed in different tissues and exhibit transcriptional responses to severe hypoxia in gill and muscle tissue, consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. The role of HIF-1alpha in response to hypoxia was further investigated in the gills and muscles of prawns using in situ hybridization. These results suggested that HIF 1alpha plays an important role in oxygen sensing and homeostasis in M. nipponense. PMID- 26883382 TI - Cu-Catalyzed C-H Trifluoromethylation of 3-Arylprop-1-ynes for the Selective Construction of Allenic Csp(2)-CF3 and Propargyl Csp(3)-CF3 Bonds. AB - A new method has been developed for the Cu-catalyzed C-H trifluoromethylation of 3-arylprop-1-ynes for the selective construction of allenic Csp(2)-CF3 and propargyl Csp(3)-CF3 bonds. The selective formation of allenic Csp(2)-CF3 and propargyl Csp(3)-CF3 bonds can be controlled by modifying the reaction conditions. PMID- 26883383 TI - Determinants of RNA metabolism in the Schizosaccharomyces pombe genome. AB - To decrypt the regulatory code of the genome, sequence elements must be defined that determine the kinetics of RNA metabolism and thus gene expression. Here, we attempt such decryption in an eukaryotic model organism, the fission yeast S. pombe. We first derive an improved genome annotation that redefines borders of 36% of expressed mRNAs and adds 487 non-coding RNAs (ncRNAs). We then combine RNA labeling in vivo with mathematical modeling to obtain rates of RNA synthesis and degradation for 5,484 expressed RNAs and splicing rates for 4,958 introns. We identify functional sequence elements in DNA and RNA that control RNA metabolic rates and quantify the contributions of individual nucleotides to RNA synthesis, splicing, and degradation. Our approach reveals distinct kinetics of mRNA and ncRNA metabolism, separates antisense regulation by transcription interference from RNA interference, and provides a general tool for studying the regulatory code of genomes. PMID- 26883386 TI - Symmetry-Supported Magnetic Blocking at 20 K in Pentagonal Bipyramidal Dy(III) Single-Ion Magnets. AB - Single-molecule magnets (SMMs) that can be trapped in one of the bistable magnetic states separated by an energy barrier are among the most promising candidates for high-density information storage, quantum processing, and spintronics. To date, a considerable series of achievements have been made. However, the presence of fast quantum tunnelling of magnetization (QTM) in most SMMs, especially in single-ion magnets (SIMs), provides a rapid relaxation route and often sets up a limit for the relaxation time. Here, we pursue the pentagonal bipyramidal symmetry to suppress the QTM and present pentagonal bipyramidal Dy(III) SIMs [Dy(Cy3PO)2(H2O)5]Cl3.(Cy3PO).H2O.EtOH (1) and [Dy(Cy3PO)2(H2O)5]Br3.2(Cy3PO).2H2O.2EtOH (2), (Cy3PO = tricyclohexyl phosphine oxide). Magnetic characterizations reveal their fascinating SMM properties with high energy barriers as 472(7) K for 1 and 543(2) K for 2, along with a record magnetic hysteresis temperature up to 20 K for 2. These results, combined with the ab initio calculations, offer an illuminating insight into the vast possibility and potential of what the symmetry rules can achieve in molecular magnetism. PMID- 26883385 TI - A human beta-III-spectrin spinocerebellar ataxia type 5 mutation causes high affinity F-actin binding. AB - Spinocerebellar ataxia type 5 (SCA5) is a human neurodegenerative disease that stems from mutations in the SPTBN2 gene encoding the protein beta-III-spectrin. Here we investigated the molecular consequence of a SCA5 missense mutation that results in a L253P substitution in the actin-binding domain (ABD) of beta-III spectrin. We report that the L253P substitution in the isolated beta-III-spectrin ABD causes strikingly high F-actin binding affinity (Kd = 75.5 nM) compared to the weak F-actin binding affinity of the wild-type ABD (Kd = 75.8 MUM). The mutation also causes decreased thermal stability (Tm = 44.6 degrees C vs 59.5 degrees C). Structural analyses indicate that leucine 253 is in a loop at the interface of the tandem calponin homology (CH) domains comprising the ABD. Leucine 253 is predicted to form hydrophobic contacts that bridge the CH domains. The decreased stability of the mutant indicates that these bridging interactions are probably disrupted, suggesting that the high F-actin binding affinity of the mutant is due to opening of the CH domain interface. These results support a fundamental role for leucine 253 in regulating opening of the CH domain interface and binding of the ABD to F-actin. This study indicates that high-affinity actin binding of L253P beta-III-spectrin is a likely driver of neurodegeneration. PMID- 26883384 TI - Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis. AB - The classical axis of renin-angiotensin system (RAS), angiotensin (Ang) converting enzyme (ACE)/Ang II/AT1, contributes to the development of non alcoholic fatty liver disease (NAFLD). However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/Mas) in hepatic steatosis is still unclear. Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2(-/y)) mice. Meanwhile, oxidative stress and inflammation were also aggravated in ACE2(-/y) mice. On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation related genes were up-regulated. In vitro, Ang-(1-7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what's more, Akt inhibitors reduced ACE2-mediated lipid metabolism. Furthermore, ACE2-mediated Akt activation could be attenuated by blockade of ATP/P2 receptor/Calmodulin (CaM) pathway. These results indicated that Ang-(1-7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. Our findings support the potential role of ACE2/Ang-(1-7)/Mas axis in prevention and treatment of hepatic lipid metabolism. PMID- 26883387 TI - Early Failures Benefit Subsequent Task Performance. AB - Animals navigate using cognitive maps. However, how they adaptively exploit these maps in changing environments is not fully understood. In this study, we investigated the problem-solving behaviors of mice in a complicated maze in which multiple routes with different intersections were available (Test 1). Although all mice eventually settled on the shortest route, mice that initially exhibited more trial-and-error exploration solved the maze more rapidly. We then introduced one or two barriers that obstructed learned routes such that mice had to establish novel roundabout detours (Tests 2/3). Solutions varied among mice but were predictable based on individual early trial-and-error patterns observed in Test 1: mice that had initially explored more extensively found better solutions. Finally, when the barriers were removed (Test 4), all mice reverted to the best solution after active exploration. Thus, early active exploration helps mice to develop optimal strategies. PMID- 26883389 TI - 'Spontaneity is a meticulously prepared art' (Oscar Wilde): Commentary on Taber et al. (2016), Associations of spontaneous self-affirmation with health care experiences and health information seeking in a national survey of US adults. PMID- 26883388 TI - Genomic profiling of a combined large cell neuroendocrine carcinoma of the submandibular gland. AB - A 69-year-old female with no previous medical history presented with a rapidly growing submandibular mass. Fine needle aspiration cytology suggested a small cell carcinoma and PET-CT showed increased 18-FDG uptake in the submandibular mass as well as in a lung mass. Submandibular resection and selective neck dissection was performed and histopathologic examination revealed a combined large-cell neuroendocrine carcinoma (LCNEC) with a squamous component and without lymph node metastases. Resection of the lung tumor revealed a papillary adenocarcinoma that was morphologically distinctly different from the LCNEC. The patient died of her lung cancer after 19 months without evidence of recurrence of the LCNEC. Genomic profiling of the salivary gland LCNEC revealed a hypodiploid genome predominated by losses of whole chromosomes or chromosome arms involving chromosomes 3p, 4, 7q, 10, 11, 13, 16q and gains of 3q and 16p. In addition, there was a segmental gain of 9p23-p22.3 including the NFIB oncogene. Continued studies of salivary gland LCNEC may provide new knowledge concerning potential diagnostic biomarkers and may ultimately also lead to the identification of new treatment targets for patients with these aggressive carcinomas. PMID- 26883390 TI - A simple method for the production of large volume 3D macroporous hydrogels for advanced biotechnological, medical and environmental applications. AB - The development of bulk, three-dimensional (3D), macroporous polymers with high permeability, large surface area and large volume is highly desirable for a range of applications in the biomedical, biotechnological and environmental areas. The experimental techniques currently used are limited to the production of small size and volume cryogel material. In this work we propose a novel, versatile, simple and reproducible method for the synthesis of large volume porous polymer hydrogels by cryogelation. By controlling the freezing process of the reagent/polymer solution, large-scale 3D macroporous gels with wide interconnected pores (up to 200 MUm in diameter) and large accessible surface area have been synthesized. For the first time, macroporous gels (of up to 400 ml bulk volume) with controlled porous structure were manufactured, with potential for scale up to much larger gel dimensions. This method can be used for production of novel 3D multi-component macroporous composite materials with a uniform distribution of embedded particles. The proposed method provides better control of freezing conditions and thus overcomes existing drawbacks limiting production of large gel-based devices and matrices. The proposed method could serve as a new design concept for functional 3D macroporous gels and composites preparation for biomedical, biotechnological and environmental applications. PMID- 26883391 TI - Laser capture microdissection of intestinal tissue from sea bass larvae using an optimized RNA integrity assay and validated reference genes. AB - The increasing demand for a sustainable larviculture has promoted research regarding environmental parameters, diseases and nutrition, intersecting at the mucosal surface of the gastrointestinal tract of fish larvae. The combination of laser capture microdissection (LCM) and gene expression experiments allows cell specific expression profiling. This study aimed at optimizing an LCM protocol for intestinal tissue of sea bass larvae. Furthermore, a 3'/5' integrity assay was developed for LCM samples of fish tissue, comprising low RNA concentrations. Furthermore, reliable reference genes for performing qPCR in larval sea bass gene expression studies were identified, as data normalization is critical in gene expression experiments using RT-qPCR. We demonstrate that a careful optimization of the LCM procedure allows recovery of high quality mRNA from defined cell populations in complex intestinal tissues. According to the geNorm and Normfinder algorithms, ef1a, rpl13a, rps18 and faua were the most stable genes to be implemented as reference genes for an appropriate normalization of intestinal tissue from sea bass across a range of experimental settings. The methodology developed here, offers a rapid and valuable approach to characterize cells/tissues in the intestinal tissue of fish larvae and their changes following pathogen exposure, nutritional/environmental changes, probiotic supplementation or a combination thereof. PMID- 26883392 TI - Antimicrobial potency of single and combined mupirocin and monoterpenes, thymol, menthol and 1,8-cineole against Staphylococcus aureus planktonic and biofilm growth. AB - Staphylococcus aureus is one of the most commonly isolated microbes in chronic rhinosinusitis (CRS) that can be complicated due to the formation of a staphylococcal biofilm. In this study, we investigated antimicrobial efficacy of single mupirocin and three types of monoterpenes (thymol, menthol and 1,8 cineole) as well as mupirocin-monoterpene combinations against S. aureus ATCC 29213 and 5 methicilin-resistant S. aureus strains (MRSA) grown in planktonic and biofilm form. MIC against planktonic bacteria as well as minimum biofilm eliminating concentrations (MBECs) and minimum biofilm inhibitory concentrations (MBICs) were determined by TTC and MTT reduction assay, respectively. The MICs of mupirocin (0.125-0.156 MUg ml(-1)) were three orders of magnitude lower than the MICs of monoterpenes, which were as follows: thymol (0.250-0.375 mg ml(-1)) > menthol (1 mg ml(-1)) > 1,8-cineole (4-8 mg ml(-1)). Mupirocin-monoterpene combinations showed indifferent effect as compared with MICs of single substances. Mupirocin (0.016-2 mg ml(-1)) failed to destroy the biofilm. The MBECs of thymol and menthol were two- to sixfold higher than their MICs, while 1,8-cineole exerted a weak antibiofilm effect with MBECs 16- to 64-fold higher than MICs. Mixture of mupirocin and 1,8 cineole exerted a potentiated biofilm eliminating effect, mupirocin-menthol showed antagonism, while effect of thymol mupirocin mixture was inconclusive. MBICs of antimicrobials were close to their MICs, except 1,8-cineole, MBIC was about three- to fivefold higher. Dominant synergy was observed for mixtures of mupirocin and menthol or thymol, whereas mupirocin-1,8-cineol exerted an indifferent or additive biofilm inhibitory effect. Particular combinations of mupirocin and the monoterpenes could be applied in CRS therapy in order to eliminate or prevent bacterial biofilm growth. PMID- 26883393 TI - Total syntheses of codonopsinine and 4-epi-codonopsinine via gold-mediated tandem catalyzed pyrrole synthesis. AB - The total syntheses of codonopsinine (1) and 4-epi-codonopsinine (2) were accomplished. The key substituted pyrrole intermediate was constructed via gold catalyzed addition-cyclization cascade of an aminoacetaldehyde acetal derivative and a terminal alkyne. After diastereoselective reduction of the pyrrole intermediate to the corresponding 3-pyrroline derivative with zinc dust and sulfonic acid, the total synthesis of 4-epi-codonopsinine (2) was achieved via stereoselective construction of the diol by dihydroxylation. In addition, the total synthesis of codonopsinine (1) was completed through stereochemical inversion of the hydroxyl group via epoxide and subsequent ring cleavage under the acidic aqueous condition. PMID- 26883394 TI - Genome-based survey of nonribosomal peptide synthetase and polyketide synthase gene clusters in type strains of the genus Microtetraspora. PMID- 26883395 TI - Stereoselective access to tubuphenylalanine and tubuvaline: improved Mn-mediated radical additions and assembly of a tubulysin tetrapeptide analog. AB - Synthesis of tubuphenylalanine and tubuvaline (Tuv), alpha-substituted gamma amino acid building blocks for tubulysin family of antimitotic compounds, has been improved using a radical addition reaction in the presence of unprotected hydroxyl functionality. The key carbon-carbon bond construction entails stereoselective Mn-mediated photolytic additions of alkyl iodides to the C=N bond of chiral N-acylhydrazones, and generates the chiral amines in high yield with complete stereocontrol. Reductive N-N bond cleavage and alcohol oxidation converted these amino alcohols into the corresponding gamma-amino acids. The route to Tuv proceeded via peptide coupling with serine methyl ester, followed by a high-yielding sequence to convert the serine amide to a thiazole. Finally, peptide bond construction established the tubulysin framework in the form of a C terminal alcohol analog. Attempted oxidation to the C-terminal carboxylate was unsuccessful; control experiments with dipeptide 18 showed a cyclization interfered with the desired oxidation process. PMID- 26883396 TI - The c-Jun N-terminal kinase (JNK) pathway is activated in human interstitial cystitis (IC) and rat protamine sulfate induced cystitis. AB - The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. However, inflammation has been suggested to play an important role in BPS/IC. JNK downstream signaling plays an important role in numerous chronic inflammatory diseases. However, studies of the JNK pathway in BPS/IC are limited. In this study, we investigated the role of the JNK pathway in human BPS/IC and rat protamine sulfate (PS)-induced cystitis and examined the effect of the selective JNK inhibitor SP600125 on rat bladder cystitis. In our study, we demonstrated that the JNK signaling pathway was activated (the expression of JNK, c-Jun, p-JNK, p-c-Jun, IL-6 and TNF-alpha were significantly increasing in BPS/IC compared to the non-BPS/IC patients) and resulted in inflammation in human BPS/IC. Further animal models showed that the JNK pathway played an important role in the pathogenesis of cystitis. JNK inhibitors, SP600125, effectively inhibited the expression of p-JNK, p-c-Jun, IL-6 and TNF-alpha. The inhibition of these pathways had a protective effect on PS-induced rat cystitis by significantly decreasing histological score and mast cell count and improving bladder micturition function (micturition frequency significantly decreasing and bladder capacity significantly increasing). Therefore, JNK inhibition could be used as a potential treatment for BPS/IC. PMID- 26883397 TI - Quantitative Analyses of Core Promoters Enable Precise Engineering of Regulated Gene Expression in Mammalian Cells. AB - Inducible transcription systems play a crucial role in a wide array of synthetic biology circuits. However, the majority of inducible promoters are constructed from a limited set of tried-and-true promoter parts, which are susceptible to common shortcomings such as high basal expression levels (i.e., leakiness). To expand the toolbox for regulated mammalian gene expression and facilitate the construction of mammalian genetic circuits with precise functionality, we quantitatively characterized a panel of eight core promoters, including sequences with mammalian, viral, and synthetic origins. We demonstrate that this selection of core promoters can provide a wide range of basal gene expression levels and achieve a gradient of fold-inductions spanning 2 orders of magnitude. Furthermore, commonly used parts such as minimal CMV and minimal SV40 promoters were shown to achieve robust gene expression upon induction, but also suffer from high levels of leakiness. In contrast, a synthetic promoter, YB_TATA, was shown to combine low basal expression with high transcription rate in the induced state to achieve significantly higher fold-induction ratios compared to all other promoters tested. These behaviors remain consistent when the promoters are coupled to different genetic outputs and different response elements, as well as across different host-cell types and DNA copy numbers. We apply this quantitative understanding of core promoter properties to the successful engineering of human T cells that respond to antigen stimulation via chimeric antigen receptor signaling specifically under hypoxic environments. Results presented in this study can facilitate the design and calibration of future mammalian synthetic biology systems capable of precisely programmed functionality. PMID- 26883398 TI - Controlling herding in minority game systems. AB - Resource allocation takes place in various types of real-world complex systems such as urban traffic, social services institutions, economical and ecosystems. Mathematically, the dynamical process of resource allocation can be modeled as minority games. Spontaneous evolution of the resource allocation dynamics, however, often leads to a harmful herding behavior accompanied by strong fluctuations in which a large majority of agents crowd temporarily for a few resources, leaving many others unused. Developing effective control methods to suppress and eliminate herding is an important but open problem. Here we develop a pinning control method, that the fluctuations of the system consist of intrinsic and systematic components allows us to design a control scheme with separated control variables. A striking finding is the universal existence of an optimal pinning fraction to minimize the variance of the system, regardless of the pinning patterns and the network topology. We carry out a generally applicable theory to explain the emergence of optimal pinning and to predict the dependence of the optimal pinning fraction on the network topology. Our work represents a general framework to deal with the broader problem of controlling collective dynamics in complex systems with potential applications in social, economical and political systems. PMID- 26883399 TI - Psychosocial coping profiles after pain rehabilitation: associations with occupational performance and patient characteristics. AB - Purpose The aims of the present study were to assess: (i) changes in coping by use of Multidimensional Pain Inventory profiles from baseline to follow-up, (ii) associations between Adaptive Coper (AC) profiles at follow-up and improvements in occupational performance (by Canadian Occupational Performance Measure COPM) and (iii) ability to predict AC profiles at follow-up by participants' baseline characteristics. Method Data at baseline, discharge and follow-up from 525 participants in a pain rehabilitation program were analyzed with multivariate statistics. Results AC profiles increased and Dysfunctional (DYS) profiles decreased at follow-up. Clinically relevant improvements on COPM were associated with having an AC profile at follow-up. Being Nordic born, having longer education, an AC profile and higher baseline scores on satisfaction with performance predicted an AC profile at follow-up. Conclusions Pain rehabilitation seems to result in sustainable and favourable coping strategies at follow-up, and improved occupational performance is associated with favourable coping at follow up. Outcomes need to be measured independently of improved coping strategies and improvements of participant's individual goals such as difficulties to perform their most meaningful occupations. Patients at risk for unfavourable coping strategies may need modified interventions. Implications for Rehabilitation More participants reported a beneficial coping, MPI profile, in a long-term perspective after a pain rehabilitation program. Improvements on occupational performance prioritized as meaningful by each of the participants are related to adequate coping strategies at follow-up. The associations between improved occupational performance and beneficial coping profiles need to be better understood. Patients with worse initial occupational performance may need modified pain rehabilitation interventions to improve their coping strategies. PMID- 26883401 TI - Changes in iodine status among US adults, 2001-2012. AB - Urinary iodine concentrations (UICs) in the US have been reported to be stable since 1988-1994, although those in selected subgroups remained low. We aimed to investigate iodine status among adults (>=20 years) by two different criteria of assessing iodine deficiency in population. Utilizing National Health and Nutrition Examination Surveys 2001-2012, we conducted linear logistic regressions adjusting for covariates. The prevalence of <50 MUg/L UIC was higher in women than in men; increased from 11.6% (2001-2004) to 13.2% (2009-2012) at the national level and in young adults, non-Hispanic blacks (NHBs) and non-users of iodine-containing supplements (all, p <0.05); the adjusted odds ratios (95%CI) in young adults (1.54 [1.11-2.15], p = 0.0007) and NHBs (1.70 [1.15-2.52], p = 0.0078). Median UICs confirm women and NHBs being in borderline iodine status. Recognizing the critical consequence of iodine deficiency particularly in women and NHBs, regular monitoring of iodine status is important for public health in the US. PMID- 26883402 TI - Arsenic, cadmium and lead in sclerotia of Wolfiporia extensa of Yunnan, China. AB - Considering the environmental pollution, edible mushroom safety is of great concern to consumers. This study aimed at providing and evaluating data on As, Cd and Pb content of sclerotia of Wolfiporia extensa collected across Yunnan in China. For the presented survey As, Cd, and Pb concentration in sclerotia of wild and cultivated W. extensa was determined by inductively coupled plasma mass spectrometry. The results showed that As, Cd, and Pb content were below the limit promulgated by WHO, with the ranges 5.27-161, 1.51-42.1 and < 1-634 ng g(-1) dry matter. Calculated hazard quotient (HQ) and hazard index (HI) were used to evaluate the non-carcinogenic health risk from individual and combined metals via daily consumption of 50 g sclerotia. Both HQ and HI through consumption of sclerotia were below 1, indicating that weekly consumption of sclerotia at the indicated doses poses no significant health risk to an adult consumer. PMID- 26883404 TI - Implementation of a Lung Cancer Nurse Navigator Enhances Patient Care and Delivery of Systemic Therapy at the British Columbia Cancer Agency, Vancouver. AB - PURPOSE: A nurse navigator (NN) pilot project for patients with lung cancer was implemented in British Columbia, a publicly funded health-care system. The purpose was to improve referral practices, timelines, and availability of molecular testing for patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Patients with stage IIIB/IV NSCLC referred to the BC Cancer Agency, Vancouver, in 2011 and 2014, pre- and post-implementation of an NN, were included. Referral patterns, systemic therapy, radiotherapy (XRT) timelines, and molecular testing practices were compared. RESULTS: The study included 408 patients: 212 in 2011 and 196 in 2014. Medical oncology (MO) end points comparing 2011 data with 2014 findings revealed that referral rates remained stable, and the proportion of patients who received systemic therapy increased from 57% to 69% (P = .05). Time from referral to MO consult was 18 days in 2011 versus 15.5 days in 2014 (P = .11); referral to systemic treatment was reduced from 48 to 38 days (P = .016). Comparison of molecular testing showed time between referral and the epidermal growth factor (EGFR) result was reduced from 34 days in 2011 to 20 days in 2014 (P < .001); rates of testing increased from 62% to 91%, respectively (P < .001); and EGFR mutation-positive rates were 19% versus 26%, respectively (P = .26). The radiation oncology (RO) end point results were as follows: 87% of patients were referred for RO consults in 2011 versus 80% in 2014 (P = .05), and the same proportion of patients received XRT (91% v 87%, respectively). Time from referral to RO consult decreased from 10 days in 2011 to 8 days in 2014 (P = .005); and referral to XRT in 2011 and 2014 was 18 days versus 11.5 days, respectively (P < .001). CONCLUSION: Implementation of an NN was associated with reduced wait times and increased molecular testing, improving appropriate delivery of first-line targeted therapy. NN involvement facilitates correct allocation of physician and clinical resources. PMID- 26883406 TI - Implementation of a Breast/Reconstruction Surgery Coordinator to Reduce Preoperative Delays for Patients Undergoing Mastectomy With Immediate Reconstruction. AB - PURPOSE: Mastectomy with immediate reconstruction (MIR) requires coordination between breast and reconstructive surgical teams, leading to increased preoperative delays that may adversely impact patient outcomes and satisfaction. Our cancer center established a target of 28 days from initial consultation with the breast surgeon to MIR. We sought to determine if a centralized breast/reconstructive surgical coordinator (BRC) could reduce care delays. METHODS: A 60-day pilot to evaluate the impact of a BRC on timeliness of care was initiated at our cancer center. All reconstructive surgery candidates were referred to the BRC, who had access to surgical clinic and operating room schedules. The BRC worked with both surgical services to identify the earliest surgery dates and facilitated operative bookings. The median time to MIR and the proportion of MIR cases that met the time-to-treatment goal was determined. These results were compared with a baseline cohort of patients undergoing MIR during the same time period (January to March) in 2013 and 2014. RESULTS: A total of 99 patients were referred to the BRC (62% cancer, 21% neoadjuvant, 17% prophylactic) during the pilot period. Focusing exclusively on patients with a cancer diagnosis, an 18.5% increase in the percentage of cases meeting the target (P = .04) and a 7-day reduction to MIR (P = .02) were observed. CONCLUSION: A significant reduction in time to MIR was achieved through the implementation of the BRC. Further research is warranted to validate these findings and assess the impact the BRC has on operational efficiency and workflows. PMID- 26883400 TI - Uptake of PrEP and condom and sexual risk behavior among MSM during the ANRS IPERGAY trial. AB - The double-blind phase of the randomized ANRS IPERGAY trial, evaluating sexual activity-based oral HIV pre-exposure prophylaxis (PrEP), was conducted among high risk men who have sex with men (MSM). Results showed an 86% (95% CI: 40-98) relative reduction in HIV incidence among participants with tenofovir disoproxil fumarate-emtricitabine vs. placebo. The present pooled analysis aimed to analyze (i) participants' adherence to the prescribed treatment and/or condom use during sexual intercourse and (ii) sexual behavior during the double-blind phase of the study. Four hundred MSM were enrolled in the trial. Every 2 months they completed online questionnaires collecting sexual behavior and PrEP adherence data regarding their most recent sexual intercourse. A total of 2232 questionnaires (M0-M24) were analyzed. Changes over time were evaluated using a mixed model accounting for multiple measures. Irrespective of sexual partner and practice type, on average, 42.6% (min: 32.1-max: 45.8%) reported PrEP use only during their most recent episode of sexual intercourse; 29% (22.9-35.6%) reported both PrEP and condom use; 11.7% (7.2-18.9%) reported condom-use only, and 16.7% (10.8 29.6%) reported no PrEP or condom use with no significant change during the study. Scheduled (i.e., correct) PrEP use was reported on average by 59.0% (47.2 68.5%) of those reporting PrEP use during their most recent sexual intercourse. Overall, 70.3% (65.3-79.4%) and 69.3% (58.3-75.4%) of participants reported, respectively, condomless anal and condomless receptive anal intercourse during their most recent sexual encounter without significant change during follow-up. Overall, on average 83.3% (min: 70.4-max: 89.2%) of participants protected themselves by PrEP intake or condom use or both during the trial, and no increase in at-risk sexual practices was observed. None of these indicators showed significant trend during the follow-up, although we found a tendency toward decrease (p = .19) of the median number of sexual partners strengthening the absence of behavioral disinhibition. On-demand PrEP within a comprehensive HIV prevention package could improve prevention in MSM. PMID- 26883407 TI - Physician Experience and Attitudes Toward Addressing the Cost of Cancer Care. AB - PURPOSE: We surveyed US cancer doctors to examine current attitudes toward cost discussions and how they influence decision making and practice management. METHODS: We conducted a self-administered, anonymous, electronic survey of randomly selected physician ASCO members to evaluate the frequency and nature of cost discussions reported by physicians, attitudes toward discussions of cost in clinics, and potential barriers. RESULTS: A total of 333 of 2,290 physicians responded (response rate [RR], 15%; adjusted RR after omitting nonpracticing physician ASCO members, 25%), Respondent practice settings were 45% academic and 55% community/private practice. Overall, 60% reported addressing costs frequently/always in clinic, whereas 40% addressed costs rarely/never. The largest reported barrier was lack of resources to guide discussions. Those who reported frequent discussions were significantly more likely to prioritize treatments in terms of cost and believed doctors should explain patient and societal costs. A total of 36%did not believe that doctors should discuss costs with patients. Academic practitioners were significantly less likely to discuss costs (odds ratio [OR], 0.41; P = .001) and felt less prepared for such discussions (OR, 0.492; P = .005) but were more likely to consider costs to the patient (OR, 2.68; P = .02) and society (OR, 1.822; P = .02). CONCLUSION: Although the majority of respondents believe it is important to consider out-of pocket costs to patients, a substantial proportion do not discuss or consider costs of cancer care. Lack of consensus on the importance of such discussions and uncertainty regarding the optimal timing and content appear to be barriers to addressing costs of care with patients. PMID- 26883409 TI - Au nanoparticle decorated graphene nanosheets for electrochemical immunosensing of p53 antibodies for cancer prognosis. AB - The accurate quantification of the level of p53 antibodies in serum is crucial for cancer prognosis. We report a novel and sensitive label-free immunosensor based on gold nanoparticles (Au NPs) self-assembled onto electrochemically reduced graphene oxide (ERGO) for the detection of p53 antibodies. An electrografted p-aminophenol organic layer was used to immobilize graphene oxide (GO) onto the surface of screen printed carbon electrodes (SPCE). The Au NP/ERGO hybrid interface provides a large surface area for the effective immobilization of p53 antigens, as well as it ascertains the bioactivity and stability of immobilized p53 antigens. Scanning electron microscope, Raman and X-ray photoelectron spectroscopies were used to monitor the sensor fabrication and cyclic voltammetry was used to quantify the extent of Au NPs' surface coverage by p53 antigens. Square wave voltammetry (SWV) of a [Fe(CN)6](3-/4-) couple was employed to investigate the immunosensor fabrication and to monitor the binding events between p53 antigens and p53 antibodies. Under optimized experimental conditions, the biosensor displayed good sensitivity and specificity. The p53 antibodies were detected in a concentration as low as 0.088 pg mL(-1) with a linear range from 0.1 pg mL(-1) to 10 ng mL(-1). The high sensitivity of the immunosensor may derive from the high loading of p53 antibodies on Au NPs which increases the number of binding events. PMID- 26883408 TI - Molecular modeling studies to characterize N-phenylpyrimidin-2-amine selectivity for CDK2 and CDK4 through 3D-QSAR and molecular dynamics simulations. AB - CDK2 is a promising target for the development of anti-cancer agents. It is not an easy task to design CDK2-selective inhibitors which do not exhibit activity for other CDK family members, particularly CDK4, due to a high degree of structural homology among CDK family members. In this study, 4-substituted N phenylpyrimidin-2-amine derivatives as CDK2 inhibitors were examined to understand the selectivity mechanism against CDK4 using a combined approach of 3D QSAR, molecular docking, MESP, MD simulations, and binding free energy calculations. 3D-QSAR models were developed to propose structural determinants for CDK2 and CDK4 inhibition. High q(2) and r(2) values for CoMFA and CoMSIA models based on both internal and external validations suggested that the generated 3D-QSAR models may exhibit good capability to predict bioactivities of inhibitors against CDK2 or CDK4. Electrostatic potentials on the molecular surface have been discussed in detail for determining the binding affinity of studied inhibitors by combining molecular docking with MESP and Mulliken charge analyses. Binding free energy calculations suggested that the residues Gln85, Asp86, and Lys89 of CDK2 would play a critical role in selective CDK2 inhibition. The electrostatic interactions of an inhibitor with Glu144 and Asn145 of CDK4 may predominately drive CDK4 inhibition. These findings may provide a better structural understanding of the mechanism of CDK2 selective inhibition. The results obtained in the current study may provide valuable guidelines for developing novel potent and selective CDK2 inhibitors. PMID- 26883410 TI - A multifunctional upconverting nanoparticle incorporated polycationic hydrogel for near-infrared triggered and synergistic treatment of drug-resistant bacteria. AB - Recently, antibiotic drug-resistant therapies have become very important due to the emergence of antibiotic-resistant bacterial strains. The development of novel antibacterial materials has received significant attention. Here, quaternized chitosan hydrogels incorporated with NaYF4:Er/Yb/Mn@photosensitizer-doped silica (UCNPs/MB) were synthesized for effective killing of both gram-positive oxacillin resistant S. aureus (DR-S. aureus) and gram-negative kanamyclin-resistant E. coli (DR-E. coli) bacteria upon near-infrared (NIR) laser irradiation. In this system, the cationic macroporous nature of the hydrogel acts as a molecular 'anion sponge', which sucks the outer part of the anionic microbe membrane into the gel interior voids and causes microbe membrane disruption. By incorporating UCNPs/MB doped silica into the hydrogel, we have combined photodynamic therapy (PDT) with quaternized chitosan to obtain a high therapeutic index via a synergistic effect. In vitro experiments have demonstrated that our system had excellent antibacterial efficiency to both DR-S. aureus and DR-E. coli bacteria. More importantly, our new synergistic treatment modality provided an excellent therapy platform for drug-resistant bacteria, which could improve antimicrobial efficiency. PMID- 26883411 TI - Prevalence of and Risk Factors for Skin Diseases Among Army Personnel and Flood Victims During the 2011 Floods in Thailand. AB - OBJECTIVE: This study aimed to determine the prevalence of and risk factors for skin problems among flood victims and army personnel during the 2011 floods in Thailand. METHODS: To determine the prevalence of and risk factors for skin symptoms, standardized questionnaires were used to collect demographic data, current skin symptoms, history of water exposure, and sanitary behaviors. A certified dermatologist evaluated those who presented with skin problems and provided diagnoses. Univariate and multivariate analyses were performed to assess independent risk factors for skin symptoms. RESULTS: The most prevalent skin disease was irritant contact dermatitis. Flood victims showed a higher prevalence of skin symptoms compared with army personnel. Development of skin symptoms after exposure to floodwater was also observed earlier among flood victims. Having a history of skin diseases and delayed skin cleaning after exposure were also significant risk factors for the development of skin symptoms. CONCLUSION: This information might be used as guidelines for protecting military personnel and to educate the general public regarding flood disaster management. (Disaster Med Public Health Preparedness. 2016;10:570-575). PMID- 26883412 TI - Sharing Clinical Trial Data. PMID- 26883413 TI - Forensic Age Estimation. AB - BACKGROUND: Forensic age estimation is requested by courts and other government authorities so that immigrants whose real age is unknown should not suffer unfair disadvantages because of their supposed age, and so that all legal procedures to which an individual's age is relevant can be properly followed. 157 age estimations were requested in Berlin in 2014, more than twice as many as in 2004. METHODS: This review is based on pertinent articles retrieved by a selective search in the PubMed and MEDPILOT databases, supplemented by relevant recommendations and by the findings of the authors' own research. RESULTS: The essential components of age estimation are the history, physical examination, X rays of the hands, panorama films of the jaws, and, if indicated, a thin-slice CT of the medial clavicular epiphyses, provided that there is a legal basis for X ray examinations without a medical indication. Multiple methods are always used in combination, for optimal accuracy. Depending on the legal issues at hand, the examiner may be asked to estimate the individual's minimum age and/or his or her most probable age. The minimum-age concept can be used in determinations whether an individual has reached the age of legal majority. It is designed to ensure that practically all persons classified as adults have, in fact, attained legal majority, even though some other persons will be incorrectly classified as minors. CONCLUSION: Forensic age estimation lets courts and other government authorities determine the official age of persons whose actual age is unknown-in most cases, unaccompanied refugees who may be minors. The goal is to carry out age-dependent legal procedures appropriately in accordance with the rule of law. The minimum-age concept is designed to prevent the erroneous classification of minors as legal adults. PMID- 26883414 TI - Chronic Abdominal Wall Pain. AB - BACKGROUND: Chronic abdominal wall pain is a poorly recognized clinical problem despite being an important element in the differential diagnosis of abdominal pain. METHODS: This review is based on pertinent articles that were retrieved by a selective search in PubMed and EMBASE employing the terms "abdominal wall pain" and "cutaneous nerve entrapment syndrome," as well as on the authors' clinical experience. RESULTS: In 2% to 3% of patients with chronic abdominal pain, the pain arises from the abdominal wall; in patients with previously diagnosed chronic abdominal pain who have no demonstrable pathological abnormality, this likelihood can rise as high as 30% . There have only been a small number of clinical trials of treatment for this condition. The diagnosis is made on clinical grounds, with the aid of Carnett's test. The characteristic clinical feature is strictly localized pain in the anterior abdominal wall, which is often mischaracterized as a "functional" complaint. In one study, injection of local anesthesia combined with steroids into the painful area was found to relieve pain for 4 weeks in 95% of patients. The injection of lidocaine alone brought about improvement in 83-91% of patients. Long-term pain relief ensued after a single lidocaine injection in 20-30% of patients, after repeated injections in 40-50% , and after combined lidocaine and steroid injections in up to 80% . Pain that persists despite these treatments can be treated with surgery (neurectomy). CONCLUSION: Chronic abdominal wall pain is easily diagnosed on physical examination and can often be rapidly treated. Any physician treating patients with abdominal pain should be aware of this condition. Further comparative treatment trials will be needed before a validated treatment algorithm can be established. PMID- 26883415 TI - Atlanto-Occipital Joint Blockage not Mentioned. PMID- 26883416 TI - Degenerative Changes of the Vestibular Receptors as Underlying Mechanism. PMID- 26883417 TI - Hyponatremia Should Be Added. PMID- 26883418 TI - Not Trivial. PMID- 26883419 TI - In Reply. PMID- 26883421 TI - Decision on folic acid fortification in Europe must consider both risks and benefits. PMID- 26883420 TI - One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial. AB - BACKGROUND: Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. METHODS/DESIGN: INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. DISCUSSION: INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. TRIAL REGISTRATION: Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159. PMID- 26883422 TI - Erratum to: 'Characteristics associated with the consumption of malted drinks among Malaysian primary school children: findings from the MyBreakfast study'. PMID- 26883423 TI - Systematic manipulation of glutathione metabolism in Escherichia coli for improved glutathione production. AB - BACKGROUND: L-glutathione (GSH) is a non-protein thiol compound with important biological properties and is widely used in pharmaceutical, food, cosmetic and health products. The cellular GSH is determined by the activity and characteristic of GSH-synthesizing enzymes, energy and precursor supply, and degradation of formed GSH. RESULTS: In this study, genes encoding enzymes related to the precursor amino acid degradation and glycogen formation as well as GSH degradation were systematically manipulated in Escherichia coli strains over expressing gshF from Actinobacillus succinogenes. The manipulation included disrupting the precursor degradation pathways (tnaA and sdaA), eliminating L glutathione degradation (ggt and pepT), and manipulating the intracellular ATP level (disruption of glgB). However the constructed mutants showed lower levels of GshF expression. 2-D electrophoresis was performed to elucidate the reasons for this discrepancy, and the results indicated obvious changes in central metabolism and amino acid metabolism in the penta-mutant. Fed-batch culture of the penta-mutant ZJ12345 was performed where the GshF expression level was enhanced, and both the GSH production (19.10 mM) and the yield based on added L cysteine (0.76 mmol/mmol) were significantly increased. CONCLUSION: By interrupting the degradation pathways of L-cysteine, serine and GSH and blocking glycogen formation, the GSH production efficiency was significantly improved. PMID- 26883424 TI - Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model. AB - The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebral infection comprising Balb/c mice experimentally infected with the virulent isolate Nc-Spain7, the three anti malarial compounds failed to exhibit any activity, since treatment did not reduce the parasite burden in brains and lungs compared to untreated controls. Thus, these compounds were not further evaluated in pregnant mice. On the other hand, buparvaquone, shown earlier to be effective in reducing the parasite load in the lungs in an acute neosporosis disease model, was further assessed in the pregnant mouse model. Buparvaquone efficiently inhibited vertical transmission in Balb/c mice experimentally infected at day 7 of pregnancy, reduced clinical signs in the pups, but had no effect on cerebral infection in the dams. This demonstrates proof-of-concept that drug repurposing may lead to the discovery of an effective compound against neosporosis that can protect offspring from vertical transmission and disease. PMID- 26883425 TI - The neonatal mortality and its determinants in rural communities of Eastern Uganda. AB - BACKGROUND: In Uganda, neonatal mortality rate (NMR) remains high at 27 deaths per 1000 live births. There is paucity of data on factors associated with NMR in rural communities in Uganda. The objective of this study was to determine NMR as well as factors associated with neonatal mortality in the rural communities of three districts from eastern Uganda. METHODS: Data from a baseline survey of a maternal and newborn intervention in the districts of Pallisa, Kibuku and Kamuli, Eastern Uganda was analyzed. A total of 2237 women who had delivered in the last 12 months irrespective of birth outcome were interviewed in the survey. The primary outcome for this paper was neonatal mortality. The risk ratio (RR) was used to determine the factors associated with neonatal mortality using log binomial model. RESULTS: The neonatal mortality was found to be 34 per 1000 live births (95% CI = 27.1-42.8); Kamuli 31.9, Pallisa 36.5 and Kibuku 30.8. Factors associated with increased neonatal deaths were parity of 5+ (adj. RR =2.53, 95% CI =1.14-5.65) relative to parity of 4 and below, newborn low birth weight (adj. RR = 3.10, 95% CI = 1.47-6.56) and presence of newborn danger signs (adj. RR = 2.42, 95% CI = 1.04-5.62). Factors associated with lower risk of neonatal death were, home visits by community health workers' (CHW) (adj. RR =0.13, 95% CI = 0.02-0.91), and attendance of at least 4 antenatal visits (adj. RR = 0.65, 95% CI = 0.43-0.98). CONCLUSIONS: Neonatal mortality in rural communities is higher than the national average. The use of CHW's to mobilize and sensitize households on appropriate maternal and newborn care practices could play a key role in reducing neonatal mortality. PMID- 26883426 TI - Identification and functional characterization of an uncharacterized antimicrobial peptide from a ciliate Paramecium caudatum. AB - The global ever-growing concerns about multi-drug resistant (MDR) microbes leads to urgent demands for exploration of new antibiotics including antimicrobial peptides (AMPs). Here we demonstrated that a cDNA from Ciliata Paramecium caudatum, designated Pcamp1, coded for a protein with features characteristic of AMPs, which is not homologous to any AMPs currently known. Both the C-terminal 91 amino acid residues of PcAMP1, cPcAMP1, expressed in Escherichia coli and the C terminal 26 amino acid residues (predicted mature AMP), cPcAMP1/26, synthesized, underwent a coil-to-helix transition in the presence of TFE, SDS or DPC. Functional assays revealed that cPcAMP1 and cPcAMP1/26 were both able to kill Aeromonas hydrophila and Staphylococcus aureus. ELISA showed that cPcAMP1 and cPcAMP1/26 were able to bind to microbe-associated molecular pattern molecules LPS and LTA, which was further corroborated by the observations that cPcAMP1 could deposit onto the bacterial membranes. Importantly, both cPcAMP1 and cPcAMP1/26 were able to induce bacterial membrane permeabilization and depolarization, and to increase intracellular ROS levels. Additionally, cPcAMP1 and cPcAMP1/26 were not cytotoxic to mammalian cells. Taken together, our results show that PcAMP1 is a potential AMP with a membrane selectivity towards bacterial cells, which renders it a promising template for the design of novel peptide antibiotics against MDR microbes. It also shows that use of signal conserved sequence of AMPs can be an effective tool to identify potential AMPs across different animal classes. PMID- 26883427 TI - Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China. AB - BACKGROUND: Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. METHODS: Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001]. CONCLUSION: The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients. PMID- 26883428 TI - [Lymphoepithelial carcinoma of the eye]. AB - A lymphoepithelial carcinoma of the conjunctiva was excised in an 80-year-old female patient. The otorhinolaryngeal (ENT) examination did not show any abnormalities and nasopharyngeal or systemic metastases were absent. A strictly controlled clinical follow-up of the excision site was scheduled. A lymphoepithelial carcinoma of the eye is very rare and it is classified under the nasopharyngeal carcinomas. The diagnostics and therapy are an interdisciplinary task involving ENT, radiology, pathology and oncology and if the tumor cannot be completely excised, radiotherapy is also included. PMID- 26883430 TI - Atorvastatin ameliorates cognitive impairment, Abeta1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice. AB - Amyloid-beta (Abeta) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3beta (GSK3beta) pathway and deactivates GSK3beta signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Abeta and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3beta signaling and contributes to subsequent down-regulation of Abeta1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3beta signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Abeta1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3beta activity by increasing phosphorylation of GSK3beta (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3beta signaling which may contribute to down-regulation of Abeta1-42 and tau hyperphosphorylation. PMID- 26883431 TI - Neuroprotection Trials in Traumatic Brain Injury. AB - Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide. Current treatment of acute TBI includes surgical intervention when needed, followed by supportive critical care such as optimizing cerebral perfusion, preventing pyrexia, and treating raised intracranial pressure. While effective in managing the primary injury to the brain and skull, these treatment modalities do not address the complex secondary cascades that occur at a cellular level following initial injury and greatly affect the ultimate neurologic outcome. These secondary processes involve changes in ionic flux, disruption of cellular function, derangement of blood flow and the blood-brain barrier, and elevated levels of free radicals. Over the past few decades, numerous pharmacologic agents and modalities have been investigated in an attempt to interrupt these secondary processes. No neuroprotective agents currently exist that have been proven to improve neurologic outcome following TBI. However, these trials have contributed significantly to the understanding of the clinical sequelae of TBI and to improvements in the quality of care for TBI. With the experience and insights that have been accrued with the trials to date, we will be able to optimize future trial designs and refine established neurologic endpoints to better identify new therapeutic agents and further improve neurologic outcomes from this often devastating condition. PMID- 26883432 TI - Long-term follow-up of renal arteries after radio-frequency catheter-based denervation using optical coherence tomography and angiography. AB - Optical coherence tomography (OCT) imaging at the time of renal denervation (RDN) showed that procedure might cause spasm, intimal injury or thrombus formation. In the present study, we assessed the healing of renal arteries after RDN using OCT and renal angiography in long-term follow-up. OCT and renal angiography were performed in 12 patients (22 arteries) 18.41 +/- 5.83 months after RNS. There were no adverse events or complications during the long-term follow-up. In ten patients (83 %), significant reductions of blood pressure was achieved without a change of the antihypertensive medications. We demonstrated the presence of 26 areas of focal intimal thickening identified by OCT in 10 (83 %) patients and in 14 (63 %) arteries. The mean area of focal intimal thickening was 0.054 +/- 0.033 mm(2). No vessel dissection, thrombus, intimal tear or acute vasospasm were observed during the OCT analysis. Also, the quantitative angiography analysis revealed a significant reduction of the minimal and proximal lumen diameters at follow-up as compared to measurements obtained before RDN. Renal arteries have a favorable "long-term" vessel healing response after RDN. Focal intimal thickening and a modest reduction of the minimal lumen diameter may be observed after RF denervation. Further studies are needed to determine whether intravascular imaging may be helpful in evaluating the vessel healing of RF RDN. PMID- 26883429 TI - The rise and fall of insulin signaling in Alzheimer's disease. AB - The prevalence of both diabetes and Alzheimer's disease (AD) are reaching epidemic proportions worldwide. Alarmingly, diabetes is also a risk factor for Alzheimer's disease. The AD brain is characterised by the accumulation of peptides called Abeta as plaques in the neuropil and hyperphosphorylated tau protein in the form of neurofibrillary tangles within neurons. How diabetes confers risk is unknown but a simple linear relationship has been proposed whereby the hyperinsulinemia associated with type 2 diabetes leads to decreased insulin signaling in the brain, with downregulation of the PI3K/AKT signalling pathway and its inhibition of the major tau kinase, glycogen synthase kinase 3beta. The earliest studies of post mortem AD brain tissue largely confirmed this cascade of events but subsequent studies have generally found either an upregulation of AKT activity, or that the relationship between insulin signaling and AD is independent of glycogen synthase kinase 3beta altogether. Given the lack of success of beta-amyloid-reducing therapies in clinical trials, there is intense interest in finding alternative or adjunctive therapeutic targets for AD. Insulin signaling is a neuroprotective pathway and represents an attractive therapeutic option. However, this incredibly complex signaling pathway is not fully understood in the human brain and particularly in the context of AD. Here, we review the ups and downs of the research efforts aimed at understanding how diabetes modifies AD risk. PMID- 26883433 TI - Three dimensional fusion of electromechanical mapping and magnetic resonance imaging for real-time navigation of intramyocardial cell injections in a porcine model of chronic myocardial infarction. AB - For cardiac regenerative therapy intramyocardial catheter guided cell transplantations are targeted to the infarct border zone (IBZ) i.e. the closest region of viable myocardium in the vicinity of the infarct area. For optimal therapeutic effect this area should be accurately identified. However late gadolinium enhanced magnetic resonance imaging (LGE-MRI) is the gold standard technique to determine the infarct size and location, electromechanical mapping (EMM) is used to guide percutaneous intramyocardial injections to the IBZ. Since EMM has a low spatial resolution, we aim to develop a practical and accurate technique to fuse EMM with LGE-MRI to guide intramyocardial injections. LGE-MRI and EMM were obtained in 17 pigs with chronic myocardial infarction created by balloon occlusion of LCX and LAD coronary arteries. LGE-MRI and EMM datasets were registered using our in-house developed 3D CartBox image registration software toolbox to assess: (1) the feasibility of the 3D CartBox toolbox, (2) the EMM values measured in the areas with a distinct infarct transmurality (IT), and (3) the highest sensitivity and specificity of the EMM to assess IT and define the IBZ. Registration of LGE-MRI and EMM resulted in a mean error of 3.01 +/- 1.94 mm between the LGE-MRI mesh and EMM points. The highest sensitivity and specificity were found for UV <9.4 mV and bipolar voltage <1.2 mV to respectively identify IT of >=5 and >=97.5 %. The 3D CartBox image registration toolbox enables registration of EMM data on pre-acquired MRI during the EMM guided procedure and allows physicians to easily guide injections to the most optimal injection location for cardiac regenerative therapy and harness the full therapeutic effect of the therapy. PMID- 26883435 TI - Internal and External Validation of a multivariable Model to Define Hospital Acquired Pneumonia After Esophagectomy. AB - BACKGROUND: Pneumonia is an important complication following esophagectomy; however, a wide range of pneumonia incidence is reported. The lack of one generally accepted definition prevents valid inter-study comparisons. We aimed to simplify and validate an existing scoring model to define pneumonia following esophagectomy. PATIENTS AND METHODS: The Utrecht Pneumonia Score, comprising of pulmonary radiography findings, leucocyte count, and temperature, was simplified and internally validated using bootstrapping in the dataset (n = 185) in which it was developed. Subsequently, the intercept and (shrunk) coefficients of the developed multivariable logistic regression model were applied to an external dataset (n = 201) RESULTS: In the revised Uniform Pneumonia Score, points are assigned based on the temperature, the leucocyte, and the findings of pulmonary radiography. The model discrimination was excellent in the internal validation set and in the external validation set (C-statistics 0.93 and 0.91, respectively); furthermore, the model calibrated well in both cohorts. CONCLUSION: The revised Uniform Pneumonia Score (rUPS) can serve as a means to define post-esophagectomy pneumonia. Utilization of a uniform definition for pneumonia will improve inter-study comparability and improve the evaluations of new therapeutic strategies to reduce the pneumonia incidence. PMID- 26883436 TI - Area-Level Socioeconomic Factors Are Associated With Noncompletion of Pediatric Preventive Services. AB - We examined 4872 infants born consecutively, 2011-2012, and seen at 3 primary care centers to determine whether area-based socioeconomic measures were associated with noncompletion of common preventive services within the first 15 months. Addresses were geocoded and linked to census tract poverty, adult educational attainment, and household vehicle ownership rates. The quartile of patients in the highest poverty (adjusted odds ratio [aOR] 1.25; 95% confidence interval [CI] 1.01-1.54) and lowest vehicle ownership tracts (aOR 1.32; 95% CI 1.07-1.63) had significantly increased odds of service noncompletion. There were significant spatial clusters of low completion in Cincinnati's urban core. These findings have implications for preventive service delivery. PMID- 26883437 TI - Clinician-Reported Barriers to Group Visit Implementation. AB - BACKGROUND: Group visits have been shown to improve disease-oriented outcomes and satisfaction, yet many clinicians have not incorporated them into practice. We aimed to identify clinician-reported barriers that preclude clinicians from implementing group visits. METHODS: Primary care physicians from one practice based research network were surveyed regarding their experience with and barriers to group visits. The survey, developed for this study, was mailed to 246 clinicians. RESULTS: Of 107 respondents (44% response rate), those in practice <10 years were significantly more likely to have had group visit experience than those with >10 years of experience. For those without prior group visit experience, training was named as the top barrier to incorporating group visits. Those with group visit experience named staffing concerns and recruitment as the top barriers to group visit implementation. CONCLUSIONS: Primary care clinicians without prior group visit experience were less likely to endorse group visits. Addressing the modifiable barriers may enhance the incorporation of group visits into practice. PMID- 26883438 TI - Absolute Bioavailability of Ponesimod, a Selective S1P1 Receptor Modulator, in Healthy Male Subjects. AB - BACKGROUND AND OBJECTIVES: The pharmacokinetic profile of ponesimod, a sphingosine-1-phosphate receptor 1 modulator, is characterized by a rapid absorption [time to maximum concentration (t max) of 2-4 h] and a terminal half life (t 1/2) of 32 h after single-dose administration. The aim of this study was to assess additional pharmacokinetic parameters [absolute bioavailability, total clearance (CL), and volume of distribution (V ss)] in healthy male subjects. METHODS: After ensuring in a pilot phase the full pharmacokinetic profile, safety, and tolerability of a 5-mg intravenous infusion of ponesimod over 3 h (treatment A), the study proceeded to the randomized, two-way crossover, single dose (treatment A; treatment B: 10 mg oral) main phase. RESULTS: The absolute bioavailability of ponesimod was 83.8 % [90 % confidence interval (CI): 80.2 87.5]. CL and V ss (95 % CI) were 3.8 L/h (3.3-4.3) and 160 L (146.1-174.2), respectively. C max (95 % CI) was 48.5 ng/mL (43.9-53.6) and 61.4 ng/mL (55.3 68.3) after intravenous infusion and oral administration, respectively. The t 1/2 (95 % CI) following intravenous infusion was 32.9 h (28.5-38.1) and 31.7 h (27.9 36.0) following oral administration. Ponesimod administered by both routes of administration was well tolerated and resulted in transient decreases in lymphocyte count and heart rate. CONCLUSIONS: This study indicates high absolute bioavailability, low CL, and moderate V ss of ponesimod. PMID- 26883434 TI - The fibrosis-cell death axis in heart failure. AB - Cardiac stress can induce morphological, structural and functional changes of the heart, referred to as cardiac remodeling. Myocardial infarction or sustained overload as a result of pathological causes such as hypertension or valve insufficiency may result in progressive remodeling and finally lead to heart failure (HF). Whereas pathological and physiological (exercise, pregnancy) overload both stimulate cardiomyocyte growth (hypertrophy), only pathological remodeling is characterized by increased deposition of extracellular matrix proteins, termed fibrosis, and loss of cardiomyocytes by necrosis, apoptosis and/or phagocytosis. HF is strongly associated with age, and cardiomyocyte loss and fibrosis are typical signs of the aging heart. Fibrosis results in stiffening of the heart, conductivity problems and reduced oxygen diffusion, and is associated with diminished ventricular function and arrhythmias. As a consequence, the workload of cardiomyocytes in the fibrotic heart is further augmented, whereas the physiological environment is becoming less favorable. This causes additional cardiomyocyte death and replacement of lost cardiomyocytes by fibrotic material, generating a vicious cycle of further decline of cardiac function. Breaking this fibrosis-cell death axis could halt further pathological and age-related cardiac regression and potentially reverse remodeling. In this review, we will describe the interaction between cardiac fibrosis, cardiomyocyte hypertrophy and cell death, and discuss potential strategies for tackling progressive cardiac remodeling and HF. PMID- 26883440 TI - The impact of deep vein thrombosis on the risk of subsequent cardiovascular events: a 14-year follow-up study. AB - BACKGROUND: The association between deep vein thrombosis (DVT) and atherosclerosis is still controversial. METHODS: We examined the rate of subsequent symptomatic atherosclerosis in patients with unprovoked as compared to secondary DVT with a retrospectively follow-up of a cohort of patients who 14 years earlier had developed an episode of DVT not preceded by arterial cardiovascular events. We collected information on the development of coronary heart disease, ischemic stroke, peripheral artery disease or sudden otherwise unexplained death. RESULTS: We retrieved information from 138 patients with unprovoked and 123 with secondary DVT. The cumulative incidence of symptomatic atherosclerosis was 17.6% (95% CI, 8.3 to 26.0) in patients with unprovoked DVT, and 5.1% (95% CI: 0.0 to 10.7) in those with secondary DVT. After adjusting for age, sex, smoking, hypertension, diabetes and dyslipidemia, the hazard ratio (HR) for development of symptomatic atherosclerosis among patients with unprovoked DVT as compared to those with secondary DVT was 2.89 (95% CI, 1.06 to 7.88; P=0.038). CONCLUSIONS: The risk of subsequent symptomatic atherosclerosis among patients with unprovoked DVT is approximately three times as high as that of patients with secondary events. PMID- 26883439 TI - Steinmann pin augmentation versus locking plate constructs. AB - BACKGROUND: Aggressive bone neoplasms, such as giant cell tumors, often affect the proximal tibia warranting bony resection via curettage leaving behind massive defects that require extensive reconstruction. Reconstruction is usually accomplished with poly(methyl methacrylate) (PMMA) packing supplemented with an internal fixation construct. The purpose of this study is to compare Steinmann pin augmentation to locking plate constructs to determine which offers the stiffer reconstruction option. MATERIALS AND METHODS: Large defects were created below the lateral condyle of fresh frozen tibias. The defects extended for an average of 35 mm beneath the lateral plateau in the frontal plane, and from the anterior to posterior cortex in the sagittal plane. Distally the defect extended for an average of 35 mm to the metadiaphyseal junction. In the Pin group, the tibias were reconstructed with three 4-mm diameter Steinmann pins placed in the medullary canal and PMMA packing. In the Plate group, the tibias were reconstructed with a 6-hole 3.5-mm LCP Proximal locking plate fixed to the proximal-lateral tibia utilizing seven 3.5-mm screws and PMMA packing. The tibias were tested for stiffness on a MTS machine by applying up to 400 N to the tibial plateau in force control at 5 N/s. Fatigue properties were tested by applying a haversine loading waveform between 200 N and 1,200 N at 3 Hz simulating walking upstairs/downstairs. RESULTS: Locking plate constructs (801.8 +/- 78 N/mm) had greater (p = 0.041) stiffness than tibial constructs fixed with Steinmann pins (646.5 +/- 206.3 N/mm). CONCLUSIONS: Permanent deformation was similar between the Pin and Plate group; however, two tibia from the Pin group exhibited displacements >5 mm which we considered failure. LEVEL OF EVIDENCE: n/a. PMID- 26883441 TI - UEMS training requirements for angiology and vascular medicine: european standards of postgraduate medical specialist training (ETR Document). PMID- 26883442 TI - Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells. AB - The formation of fat-laden foam cells, contributing to the fatty streaks of the plaques of atheroma, is the critical early process in atherosclerosis. The previous study demonstrated that vascular smooth muscle cells (VSMCs) contain a much larger burden of the excess cholesterol in comparison with monocyte-derived macrophages in human coronary atherosclerosis, as the main origin of foam cells. It is noteworthy that VSMC-derived foam cells are deposited in subintima but not media, where VSMCs normally deposit in. Therefore, migration from media to intima is an indispensable step for a VSMC to accrue neutral lipids and form foam cell. Whether this migration occurs paralleled with or prior to the formation of foam cell is still unclear. Herein, the present study was designed to test the VSMC migratory capability in the process of foam cell formation induced by oxidized low-density lipoprotein (oxLDL). In conclusion, we provide evidence that oxLDL induces the VSMC-derived foam cells formation with increased migration ability and MMP-9 expression, which were partly attributed to the impaired SIRT1 and enhanced nuclear factor-kappa B (NF-kappaB) activity. As activation of transient receptor potential vanilloid type 1 (TRPV1) has been reported to have anti atherosclerotic effects, we investigated its role in oxLDL-treated VSMC migration. It is found that activating TRPV1 by capsaicin inhibits VSMC foam cell formation and the accompanied migration through rescuing the SIRT1 and suppressing NF-kappaB signaling. The present study provides evidence that SIRT1 may be a promising intervention target of atherosclerosis, and raises the prospect of TRPV1 in prevention and treatment of atherosclerosis. PMID- 26883443 TI - Mechanisms of nuclear lamina growth in interphase. AB - The nuclear lamina represents a multifunctional platform involved in such diverse yet interconnected processes as spatial organization of the genome, maintenance of mechanical stability of the nucleus, regulation of transcription and replication. Most of lamina activities are exerted through tethering of lamina associated chromatin domains (LADs) to the nuclear periphery. Yet, the lamina is a dynamic structure demonstrating considerable expansion during the cell cycle to accommodate increased number of LADs formed during DNA replication. We analyzed dynamics of nuclear growth during interphase and changes in lamina structure as a function of cell cycle progression. The nuclear lamina demonstrates steady growth from G1 till G2, while quantitative analysis of lamina meshwork by super resolution microscopy revealed that microdomain organization of the lamina is maintained, with lamin A and lamin B microdomain periodicity and interdomain gap sizes unchanged. FRAP analysis, in contrast, demonstrated differences in lamin A and B1 exchange rates; the latter showing higher recovery rate in S-phase cells. In order to further analyze the mechanism of lamina growth in interphase, we generated a lamina-free nuclear envelope in living interphase cells by reversible hypotonic shock. The nuclear envelope in nuclear buds formed after such a treatment initially lacked lamins, and analysis of lamina formation revealed striking difference in lamin A and B1 assembly: lamin A reassembled within 30 min post-treatment, whereas lamin B1 did not incorporate into the newly formed lamina at all. We suggest that in somatic cells lamin B1 meshwork growth is coordinated with replication of LADs, and lamin A meshwork assembly seems to be chromatin independent process. PMID- 26883444 TI - Association of bone mineral density and diabetic retinopathy in diabetic subjects: the 2008-2011 Korea National Health and Nutrition Examination Survey. AB - Because diabetic retinopathy increases fracture risk, we studied the association between bone mineral density (BMD) and diabetic retinopathy in a nationally representative sample. A significant association between the presence of diabetic retinopathy and low BMD was observed. Therefore, diabetic retinopathy might be considered as a marker of low BMD. INTRODUCTION: Several diabetic complications, including nephropathy, retinopathy, and peripheral neuropathy, are associated with a higher fracture risk in diabetic subjects. However, in contrast to diabetic nephropathy and peripheral neuropathy, which are associated with low bone mineral density (BMD), little is known about the association between BMD and diabetic retinopathy. The aim of the present study was to determine whether the prevalence of diabetic retinopathy is associated with BMD. METHODS: This cross sectional study included a nationally representative sample consisting of 4357 men aged 50 years and older and 4392 postmenopausal women who participated in the Korea National Health and Nutritional Examination Survey (KNHANES) from 2008 to 2011 and underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) and diabetic retinopathy assessments using seven standard gradable photographs. RESULTS: The diabetic women with retinopathy had lower mean BMD at all measured sites than those without retinopathy, although the BMD difference between the two groups was small (3-5 %). In addition, the diabetic women with retinopathy were 2.27 times more likely to have osteoporosis following adjustments for all clinically relevant covariates. However, the prevalence of diabetes mellitus (DM) or diabetic retinopathy was not associated with the prevalence of osteoporosis in men. CONCLUSIONS: This study has shown that the presence of diabetic retinopathy is significantly associated with a reduced BMD and increased prevalence of osteoporosis in diabetic women. PMID- 26883445 TI - The Site Frequency Spectrum for General Coalescents. AB - General genealogical processes such as Lambda- and Xi-coalescents, which respectively model multiple and simultaneous mergers, have important applications in studying marine species, strong positive selection, recurrent selective sweeps, strong bottlenecks, large sample sizes, and so on. Recently, there has been significant progress in developing useful inference tools for such general models. In particular, inference methods based on the site frequency spectrum (SFS) have received noticeable attention. Here, we derive a new formula for the expected SFS for general Lambda- and Xi-coalescents, which leads to an efficient algorithm. For time-homogeneous coalescents, the runtime of our algorithm for computing the expected SFS is O(n2) where n is the sample size. This is a factor of[Formula: see text]faster than the state-of-the-art method. Furthermore, in contrast to existing methods, our method generalizes to time-inhomogeneous Lambda and Xi-coalescents with measures that factorize as[Formula: see text] and [Formula: see text]respectively, where zeta denotes a strictly positive function of time. The runtime of our algorithm in this setting is[Formula: see text]We also obtain general theoretical results for the identifiability of the Lambda measure when zeta is a constant function, as well as for the identifiability of the function zeta under a fixed Xi measure. PMID- 26883446 TI - Insulinotropic compounds decrease endothelial cell survival. AB - OBJECTIVES: Hyperglycemia induces damage of vascular endothelial cells leading to diabetic complications. We investigated the effects of insulinotropic compounds and elevated glucose on endothelial cells in the absence or presence of vascular endothelial growth factor (VEGF). RESULTS: Human umbilical vein endothelial cells (HUVECs) were treated with glibenclamide, repaglinide and insulinotropic imidazolines at high glucose concentration in the presence or absence of VEGF and viability, proliferation and nitric oxide production were measured. Hyperglycemia inhibited pro-survival effects of VEGF on endothelial cells. Glibenclamide and repaglinide decreased HUVEC viability at elevated glucose concentration in the absence but not in the presence of VEGF, without affecting HUVEC proliferation. Repaglinide also had some positive influence on HUVEC function elevating NO production in the presence of VEGF. Imidazolines showed different activities on endothelial cell survival. Efaroxan diminished HUVEC viability at elevated glucose concentration in the presence, however not in the absence of VEGF, while RX871024 decreased HUVEC survival regardless of the presence of VEGF. SIGNIFICANCE OF THE STUDY: Our data demonstrate an important interplay between the actual insulinotropic compounds, VEGF and ambient glucose concentration affecting the survival of the vascular endothelial cells. Consequently, this interplay needs to be taken into consideration when designing novel oral antidiabetic compounds. PMID- 26883447 TI - Ants in the Hospital Environment: Ecological Parameters as Support for Future Management Strategies. AB - Urban ants cause many losses to human society, and they represent a potential threat to public health in hospital environments due to their ability to transport pathogenic organisms. We evaluated several ecological parameters (richness, abundance, constancy, and evenness), their fluctuation during the seasons, and identified species that occur outside the natural range of the ant fauna of a hospital environment, as support for future management strategies. Ant sampling was held every 2 months by using attractive bait traps in the morning and evening, leading to the sampling of 10,342 individuals belonging to six subfamilies and 26 species. Myrmicinae showed higher richness (n = 12) and abundance (n = 7336), with Pheidole susannae Forel being the most abundant species. The most constant species (100%) were P. susannae and Tetramorium simillimum (Smith). Among the most abundant species, Monomorium floricola (Jerdon) and Tapinoma melanocephalum (Fabricius) are considered as species that occur outside the natural range. No difference was observed between species richness and abundance. The Shannon (2.247), dominance (0.1395) and evenness indices (0.6897) indicated a stability of the community throughout the year with high diversity and low dominance of species. The sampled data constitute a new series of information on a long-term ecological approach to support future management strategies in hospital environments and allow for more efficient pest control. PMID- 26883448 TI - A shape-anisotropic reflective polarizer in a stomatopod crustacean. AB - Many biophotonic structures have their spectral properties of reflection 'tuned' using the (zeroth-order) Bragg criteria for phase constructive interference. This is associated with a periodicity, or distribution of periodicities, parallel to the direction of illumination. The polarization properties of these reflections are, however, typically constrained by the dimensional symmetry and intrinsic dielectric properties of the biological materials. Here we report a linearly polarizing reflector in a stomatopod crustacean that consists of 6-8 layers of hollow, ovoid vesicles with principal axes of ~550 nm, ~250 nm and ~150 nm. The reflection of unpolarized normally incident light is blue/green in colour with maximum reflectance wavelength of 520 nm and a degree of polarization greater than 0.6 over most of the visible spectrum. We demonstrate that the polarizing reflection can be explained by a resonant coupling with the first-order, in plane, Bragg harmonics. These harmonics are associated with a distribution of periodicities perpendicular to the direction of illumination, and, due to the shape-anisotropy of the vesicles, are different for each linear polarization mode. This control and tuning of the polarization of the reflection using shape anisotropic hollow scatterers is unlike any optical structure previously described and could provide a new design pathway for polarization-tunability in man-made photonic devices. PMID- 26883449 TI - Reconstructing the plinian and co-ignimbrite sources of large volcanic eruptions: A novel approach for the Campanian Ignimbrite. AB - The 39 ka Campanian Ignimbrite (CI) super-eruption was the largest volcanic eruption of the past 200 ka in Europe. Tephra deposits indicate two distinct plume forming phases, Plinian and co-ignimbrite, characteristic of many caldera forming eruptions. Previous numerical studies have characterized the eruption as a single-phase event, potentially leading to inaccurate assessment of eruption dynamics. To reconstruct the volume, intensity, and duration of the tephra dispersal, we applied a computational inversion method that explicitly accounts for the Plinian and co-ignimbrite phases and for gravitational spreading of the umbrella cloud. To verify the consistency of our results, we performed an additional single-phase inversion using an independent thickness dataset. Our better-fitting two-phase model suggests a higher mass eruption rate than previous studies, and estimates that 3/4 of the total fallout volume is co-ignimbrite in origin. Gravitational spreading of the umbrella cloud dominates tephra transport only within the first hundred kilometres due to strong stratospheric winds in our best-fit wind model. Finally, tephra fallout impacts would have interrupted the westward migration of modern hominid groups in Europe, possibly supporting the hypothesis of prolonged Neanderthal survival in South-Western Europe during the Middle to Upper Palaeolithic transition. PMID- 26883450 TI - Intraoperative intravital microscopy permits the study of human tumour vessels. AB - Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ~50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID- 26883452 TI - A der(11)t(4;11)(q21;p15) in a T-ALL/LBL patient. AB - Translocation t(4;11)(q21;p15) is a rare recurrent change associated to T-cell acute leukemia. In most cases, this alteration appears as the only abnormality or as part of a simple karyotype. In this report, we present the first case of T acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) with the unbalanced translocation der(11)t(4;11)(q21;p15) as part of a very complex karyotype with multiple chromosome abnormalities, most of them not previously described in the literature. FISH (fluorescence in situ hybridization) and spectral karyotype (HiSKY) analysis confirmed the presence of complex alterations. The patient, a 16 year-old male, showed poor response to treatment and short survival (11 months). A detailed review of previously reported cases with t(4;11)(q21;p15) is also provided. The description of this type of alterations may contribute to the identification of new molecular mechanism associated to neoplastic development. PMID- 26883451 TI - Overview of recurrent chromosomal losses in retinoblastoma detected by low coverage next generation sequencing. AB - Genes are frequently lost or gained in malignant tumors and the analysis of these changes can be informative about the underlying tumor biology. Retinoblastoma is a pediatric intraocular malignancy, and since deletions in chromosome 13 have been described in this tumor, we performed genome wide sequencing with the Illumina platform to test whether recurrent losses could be detected in low coverage data from DNA pools of Rb cases. An in silico reference profile for each pool was created from the human genome sequence GRCh37p5; a chromosome integrity score and a graphics 40 Kb window analysis approach, allowed us to identify with high resolution previously reported non random recurrent losses in all chromosomes of these tumors. We also found a pattern of gains and losses associated to clear and dark cytogenetic bands respectively. We further analyze a pool of medulloblastoma and found a more stable genomic profile and previously reported losses in this tumor. This approach facilitates identification of recurrent deletions from many patients that may be biological relevant for tumor development. PMID- 26883453 TI - Oxaliplatin administration increases expression of the voltage-dependent calcium channel alpha2delta-1 subunit in the rat spinal cord. AB - Oxaliplatin is a chemotherapeutic agent that is effective against various types of cancer including colorectal cancer. Acute cold hyperalgesia is a serious side effect of oxaliplatin treatment. Although the therapeutic drug pregabalin is beneficial for preventing peripheral neuropathic pain by targeting the voltage dependent calcium channel alpha2delta-1 (Cavalpha2delta-1) subunit, the effect of oxaliplatin-induced acute cold hypersensitivity is uncertain. To analyze the contribution of the Cavalpha2delta-1 subunit to the development of oxaliplatin induced acute cold hypersensitivity, Cavalpha2delta-1 subunit expression in the rat spinal cord was analyzed after oxaliplatin treatment. Behavioral assessment using the acetone spray test showed that 6 mg/kg oxaliplatin-induced cold hypersensitivity 2 and 4 days later. Oxaliplatin-induced acute cold hypersensitivity 4 days after treatment was significantly inhibited by pregabalin (50 mg/kg, p.o.). Oxaliplatin (6 mg/kg, i.p.) treatment increased the expression level of Cavalpha2delta-1 subunit mRNA and protein in the spinal cord 2 and 4 days after treatment. Immunohistochemistry showed that oxaliplatin increased Cavalpha2delta-1 subunit protein expression in superficial layers of the spinal dorsal horn 2 and 4 days after treatment. These results suggest that oxaliplatin treatment increases Cavalpha2delta-1 subunit expression in the superficial layers of the spinal cord and may contribute to functional peripheral acute cold hypersensitivity. PMID- 26883454 TI - Intrajejunal infusion of 2-monoacylglycerol reduced food intake without inducing diarrhea in rats. AB - Some nutrients, such as carbohydrate, fat and protein, are known to stimulate satiety. However, the effect of sn-2-monoacylglycerol (2-MG), one of the digestive products of triglycerides, on food intake is still unclear. In the present study, the effects of 2-MG on food intake and diarrhea were evaluated and compared with long-chain fatty acid (LCFA) in rats by intrajejunal infusion. Intrajejunal infusion of 2-MG reduced food intake. In addition, 2-MG did not induce diarrhea at the condition that it comparably reduced food intake as compared with LCFA. These results suggest that 2-MG stimulates satiety without inducing diarrhea, different from LCFA. PMID- 26883455 TI - P-glycoprotein inhibitors improve effective dose and time of pregabalin to inhibit intermittent cold stress-induced central pain. AB - Pregabalin (PGB) is a valuable therapeutic drug against chronic pain. Here we attempted to perform the combinatorial drug therapy with P-glycoprotein (P-gp) inhibitors to lower therapeutic dosage of PGB in the intermittent cold stress induced fibromyalgia-like pain model. Single intracerebroventricular (i.c.v.) PGB injection exerted long-lasting anti-hyperalgesic effects for 72 h, while the effect of PGB given intraperitoneally (i.p.) disappeared within 3 h. Importantly, the pretreatment with P-gp inhibitors markedly prolonged the PGB (i.p.) effects, which lasted for 72 h. These results suggest that the combinatorial treatment with P-gp inhibitor enables the prolongation of dose-interval for PGB. PMID- 26883456 TI - Peripheral HMGB1-induced hyperalgesia in mice: Redox state-dependent distinct roles of RAGE and TLR4. AB - Nuclear HMGB1 that contains 3 cysteine residues is acetylated and secreted to the extracellular space, promoting inflammation via multiple molecules such as RAGE and TLR4. We thus evaluated and characterized the redox state-dependent effects of peripheral HMGB1 on nociception. Intraplantar (i.pl.) administration of bovine thymus-derived HMGB1 (bt-HMGB1), all-thiol HMGB1 (at-HMGB1) or disulfide HMGB1 (ds-HMGB1) caused long-lasting mechanical hyperalgesia in mice. The hyperalgesia following i.pl. bt-HMGB1 or at-HMGB1 was attenuated by RAGE inhibitors, while the ds-HMGB1-induced hyperalgesia was abolished by a TLR4 antagonist. Thus, nociceptive processing by peripheral HMGB1 is considered dependent on its redox states. PMID- 26883457 TI - Levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain in conscious rats. AB - Levodopa possesses antinociceptive actions against several somatic pain conditions. However, we do not know at this moment whether levodopa is also effective to visceral pain. The present study was therefore performed to clarify whether levodopa is effective to visceral pain and its mechanisms. Visceral sensation was evaluated by colonic distension-induced abdominal withdrawal reflex (AWR) in conscious rats. Subcutaneously (80 mg/rat) or intracisternally (2.5 MUg/rat) administered levodopa significantly increased the threshold of colonic distension-induced AWR in conscious rats. The dose difference to induce the antinociceptive action suggests levodopa acts centrally to exert its antinociceptive action against colonic distension. While neither sulpiride, a D2 dopamine receptor antagonist, nor SCH23390, a D1 dopamine receptor antagonist by itself changed the threshold of colonic distension-induced AWR, the intracisternally injected levodopa-induced antinociceptive action was significantly blocked by pretreatment with subcutaneously administered sulpiride but not SCH23390. Treatment with intracisternal SB334867, an orexin 1 receptor antagonist, significantly blocked the subcutaneously administered levodopa induced antinociceptive action. These results suggest that levodopa acts centrally to induce an antinociceptive action against colonic distension through activation of D2 dopamine receptors and the orexinergic system in the brain. PMID- 26883458 TI - Human leukocyte antigen (HLA) DQ2/DQ8 prevalence in recurrent pregnancy loss women. AB - OBJECTIVE: Over the last few years, medical scholars have reported the significant association between recurrent pregnancy loss (RPL) and celiac disease (CD). Various pathogenic mechanisms underlying the pregnancy failure in CD have been suggested: among them the ability of anti-transglutaminase antibodies to impair the trophoblast invasiveness and endometrial endothelial cells differentiation and disrupt early placentation. CD shows a complex non-Mendelian pattern of inheritance, involving major histocompatibility complex (MHC) genes. The strongest effects are mapped to the classical human leukocyte antigen (HLA) DQA1 and HLA-DQB1 genes. Specifically, the common haplotypes DQ2.5, DQ2.2, and DQ8 have been shown to increase CD risk by six-fold on average. MHC region contains genes with immunological functions and is responsible for the strongest association signals observed in most immune-mediated diseases. The aim of our study was to investigate the prevalence of the HLA-DQ2/DQ8 haplotypes in RPL, outside of CD. METHODS: The study population included women with history of RPL (>=3 spontaneous pregnancy losses) and women with at least two previous uncomplicated term pregnancies (control group, CTR). All women gave their informed consent to use their data for research purposes. RESULTS: 97 RPL women and 55 CTR were considered in the study. Mean age of the RPL sample was 37.7 (standard deviation, SD, 3.0; min 27; max 39). Mean age of the control group was 35.6 (SD 3.0; min 26years; m, max 38). A significantly increased prevalence of HLA-DQ2/DQ8 haplotype positivity was found in RPL population compared to control women (52.6% vs 23.6%; p<0.01). CONCLUSIONS: Our observations show for the first time a higher proportion of individuals HLA DQ2/DQ8 positive in women with RPL as compared to controls (and to general population estimates). Further studies are needed to better understand (i) the possible pathogenic mechanism to this observation; (ii) the clinical and therapeutic implications of our observation in order to provide a new approach to RPL couples. PMID- 26883459 TI - Biotherapies in large vessel vasculitis. AB - Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-alpha drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV. PMID- 26883460 TI - Autoantibody pain. AB - As autoantibodies bind to target tissues, Fc-region dependent inflammation can induce pain via mediators exciting nociceptors. But recently another possibility has emerged, where autoantibody binding to nociceptors can directly cause pain, without inflammation. This is thought to occur as a result of Fab-region mediated modification of nerve transduction, transmission, or neuropeptide release. In three conditions, complex regional pain syndrome, anti-voltage gated potassium channel complex autoimmunity, and chronic fatigue syndrome, all associated with no or only little inflammation, initial laboratory-, and clinical trial-results have suggested a potential role for autoantibody-mediated mechanisms. More research assessing the pathogenic roles of autoantibodies in these and other chronic pain conditions is required. The concept of autoantibody-mediated pain offers hope for the development of novel therapies for currently intractable pains. PMID- 26883461 TI - Obesity and rhinitis in a nationwide study of children and adults in the United States. AB - BACKGROUND: Obesity has been associated with higher risk of asthma and asthma severity both in children and adults. However, studies evaluating the relation between obesity and rhinitis have yielded conflicting results. METHODS: We performed a cross-sectional study of obesity indicators and rhinitis using data from 8165 participants in the 2005-2006 National Health and Nutrition Examination Survey. Allergic rhinitis was defined as physician-diagnosed hay fever or allergy, the presence of symptoms in the past 12 months, and at least 1 positive allergen-specific IgE level. Nonallergic rhinitis was defined as a physician's diagnosis and symptoms but no positive allergen-specific IgE levels. Multivariate regression was used to assess the relationship between obesity and rhinitis in children and adults. RESULTS: In adults, overweight or obesity was associated with increased odds of nonallergic rhinitis (adjusted odds ratio, 1.43; 95% CI, 1.06-1.93; P = .02). Similarly, central obesity was associated with increased odds of nonallergic rhinitis in adults (adjusted odds ratio, 1.61; 95% CI, 1.20 2.16; P < .01). In an analysis stratified by sex, the observed associations were attenuated and became nonstatistically significant in female adults but remained significant in male adults. Overweight, obesity, or central obesity were not associated with allergic rhinitis in adults. In children, central obesity was associated with reduced odds of allergic rhinitis (adjusted odds ratio, 0.35; 95% CI, 0.19-0.64; P < .01). After stratification by sex, this association was similar in female and male children. CONCLUSIONS: In adults, obesity is associated with increased odds of nonallergic rhinitis, particularly in male subjects. In children, central obesity is associated with reduced odds of allergic rhinitis, regardless of sex. PMID- 26883462 TI - RNA sequencing reveals the consequences of a novel insertion in dedicator of cytokinesis-8. PMID- 26883463 TI - Chemokine release from human rhinovirus-infected airway epithelial cells promotes fibroblast migration. AB - BACKGROUND: Thickening of the lamina reticularis, a feature of remodeling in the asthmatic airways, is now known to be present in young children who wheeze. Human rhinovirus (HRV) infection is a common trigger for childhood wheezing, which is a risk factor for subsequent asthma development. We hypothesized that HRV-infected epithelial cells release chemoattractants to recruit fibroblasts that could potentially contribute to thickening of the lamina reticularis. OBJECTIVE: We sought to investigate whether conditioned medium from HRV-infected epithelial cells can trigger directed migration of fibroblasts. METHODS: Human bronchial epithelial cells were exposed to medium alone or infected with HRV-16. Conditioned medium from both conditions were tested as chemoattractants for human bronchial fibroblasts in the xCELLigence cell migration apparatus. RESULTS: HRV conditioned medium was chemotactic for fibroblasts. Treatment of fibroblasts with pertussis toxin, an inhibitor of Galphai-coupled receptors, prevented their migration. Production of epithelial chemoattractants required HRV replication. Multiplex analysis of epithelial supernatants identified CXCL10, CXCL8, and CCL5 as Galphai-coupled receptor agonists of potential interest. Subsequent analysis confirmed that fibroblasts express CXCR3 and CXCR1 receptors and that CXCL10 and, to a lesser extent, CXCL8, but not CCL5, are major contributors to fibroblast migration caused by HRV-conditioned medium. CONCLUSION: CXCL10 and CXCL8 produced from HRV-infected epithelial cells are chemotactic for fibroblasts. This raises the possibility that repeated HRV infections in childhood could contribute to the initiation and progression of airway remodeling in asthmatic patients by recruiting fibroblasts that produce matrix proteins and thicken the lamina reticularis. PMID- 26883465 TI - Meeting Organocatalysis with Drug Discovery: Asymmetric Synthesis of 3,3' Spirooxindoles Fused with Tetrahydrothiopyrans as Novel p53-MDM2 Inhibitors. AB - An organocatalytic enantioselective Michael-Michael cascade reaction is developed for the synthesis of chiral spirotetrahydrothiopyrans. This highly functionalized scaffold was assembled in moderate to good yield (55-74%) and excellent diastereo and enantioselectivities (>30:1 dr, >= 99% ee) with the creation of four consecutive stereogenic centers. The novel spiro-oxindole scaffold is validated as a new class of p53-MDM2 protein-protein interaction inhibitors with good antitumor activity. PMID- 26883464 TI - T-cell epitope conservation across allergen species is a major determinant of immunogenicity. AB - BACKGROUND: Patients with pollen allergies are frequently polysensitized. Pollens contain epitopes that are conserved across multiple species. OBJECTIVE: We sought to demonstrate that cross-reactive T cells that recognize conserved epitopes show higher levels of expansion than T cells recognizing monospecific epitopes because of more frequent stimulation. METHOD: RNA was sequenced from 9 pollens, and the reads were assembled de novo into more than 50,000 transcripts. T-cell epitopes from timothy grass (Phleum pratense) were examined for conservation in these transcripts, and this was correlated to their ability to induce T-cell responses. T cells were expanded in vitro with P pratense-derived peptides and tested for cross-reactivity to pollen extracts in ELISpot assays. RESULTS: We found that antigenic proteins are more conserved than nonimmunogenic proteins in P pratense pollen. Additionally, P pratense epitopes that were highly conserved across pollens elicited more T-cell responses in donors with grass allergy than less conserved epitopes. Moreover, conservation of a P pratense peptide at the transcriptomic level correlated with the ability of that peptide to trigger T cells that were cross-reactive with other non-P pratense pollen extracts. CONCLUSION: We found a correlation between conservation of peptides in plant pollens and their T-cell immunogenicity within P pratense, as well as their ability to induce cross-reactive T-cell responses. T cells recognizing conserved epitopes might be more prominent because they can be stimulated by a broader range of pollens and thereby drive polysensitization in allergic donors. We propose that conserved peptides could potentially be used in diagnostic or immunomodulatory approaches that address the issue of polysensitization and target multiple pollen allergies. PMID- 26883466 TI - The mitochondrial genome and ribosomal operon of Brachycladium goliath (Digenea: Brachycladiidae) recovered from a stranded minke whale. AB - Members of the Brachycladiidae are known to cause pathologies implicated in cetacean strandings and it is important to develop accurate diagnostic markers to differentiate these and other helminths found in cetaceans. Brachycladium goliath (van Beneden, 1858) is a large trematode found, as adults, usually in the hepatic (bile) and pancreatic ducts of various cetaceans. Complete sequences were determined for the entire mitochondrial genome, and phylogenetically informative nuclear genes contained within the ribosomal operon, from a small piece of an individual worm taken from a common minke whale Balaenoptera acutorostrata Lacepede, 1804. Genomic DNA was sequenced using an Illumina MiSeq platform. The mtDNA is 15,229 bp in length consisting of 12 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding regions of which the larger is comprised of 4 tandemly repeated units (260 bp each). The ribosomal RNA operon is 9297 bp long. These data provide a rich resource of molecular markers for diagnostics, phylogenetics and population genetics in order to better understand the role, and associated pathology of helminth infections in cetaceans. PMID- 26883467 TI - Carbon storage in Chinese grassland ecosystems: Influence of different integrative methods. AB - The accurate estimate of grassland carbon (C) is affected by many factors at the large scale. Here, we used six methods (three spatial interpolation methods and three grassland classification methods) to estimate C storage of Chinese grasslands based on published data from 2004 to 2014, and assessed the uncertainty resulting from different integrative methods. The uncertainty (coefficient of variation, CV, %) of grassland C storage was approximately 4.8% for the six methods tested, which was mainly determined by soil C storage. C density and C storage to the soil layer depth of 100 cm were estimated to be 8.46 +/- 0.41 kg C m(-2) and 30.98 +/- 1.25 Pg C, respectively. Ecosystem C storage was composed of 0.23 +/- 0.01 (0.7%) above-ground biomass, 1.38 +/- 0.14 (4.5%) below-ground biomass, and 29.37 +/- 1.2 (94.8%) Pg C in the 0-100 cm soil layer. Carbon storage calculated by the grassland classification methods (18 grassland types) was closer to the mean value than those calculated by the spatial interpolation methods. Differences in integrative methods may partially explain the high uncertainty in C storage estimates in different studies. This first evaluation demonstrates the importance of multi-methodological approaches to accurately estimate C storage in large-scale terrestrial ecosystems. PMID- 26883468 TI - Autophagy protects podocytes from sublytic complement induced injury. AB - Podocyte injury induced by sublytic complement attack is the main feature of membranous nephropathy (MN). This study aimed at investigating the impact of sublytic complement attack-related autophagy on podocyte injury in vitro. Here, we show that sublytic complement attack enhances MPC5 podocyte autophagy in vitro. Inhibition of autophagy by treatment with 3-methyladenine (3-MA) significantly increased sublytic complement attack-induced changes in the injury related morphology, stress fiber, and podocyte apoptosis, but decreased the survival and adhesion of MPC5 podocytes. In contrast, promotion of autophagy by treatment with rapamycin mitigated sublytic complement attack-induced changes in the injury-related morphology, stress fiber, and podocyte apoptosis, but increased the survival and adhesion of MPC5 podocytes. These data suggest that autophagy may protect podocytes from sublytic complement attack-induced injury in vitro. PMID- 26883470 TI - A Grand Challenge: Unbiased Phenotypic Function of Metabolites from Jaspis splendens against Parkinson's Disease. AB - A grand challenge in natural product chemistry is to determine the biological effects of all natural products. A phenotypic approach is frequently used for determining the activity of a compound and its potential impact on a disease state. Chemical investigation of a specimen of Jaspis splendens collected from the Great Barrier Reef resulted in the isolation of a new pterin derivative, jaspterin (1), a new bisindole alkaloid, splendamide (2), and a new imidazole alkaloid, jaspnin A (3) TFA salt. Jaspamycin (8) and 6-bromo-1H-indole-3 carboximidamide (16) are reported for the first time as naturally occurring metabolites. Known nucleosides (4-7, 9, 10), aglycones (11-13), indole alkaloids (14, 15, 17), and jaspamide peptides (18-22) were also isolated. The structures of the three new compounds 1-3 were unambiguously elucidated based on NMR and mass spectroscopic data. Jaspnin A (3) contained a rare thiomethylated imidazolinium unit. Coupling an unbiased phenotypic assay using a human olfactory neurosphere-derived cell model of Parkinson's disease to all of the natural products from the species J. splendens allowed the phenotypic profiles of the metabolites to be investigated. PMID- 26883469 TI - Ubiquitin-specific protease 4 controls metastatic potential through beta-catenin stabilization in brain metastatic lung adenocarcinoma. AB - Brain metastasis is the most common type of intracranial cancer and is the main cause of cancer-associated mortality. Brain metastasis mainly originates from lung cancer. Using a previously established in vitro brain metastatic model, we found that brain metastatic PC14PE6/LvBr4 cells exhibited higher expression of beta-catenin and increased migratory activity than parental PC14PE6 cells. Knockdown of beta-catenin dramatically suppressed the motility and invasiveness of PC14PE6/LvBr4 cells, indicating beta-catenin is involved in controlling metastatic potential. Since beta-catenin protein was increased without a significant change in its mRNA levels, the mechanism underlying increased beta catenin stability was investigated. We found that ubiquitin-specific protease 4 (USP4), recently identified as a beta-catenin-specific deubiquitinylating enzyme, was highly expressed in PC14PE6/LvBr4 cells and involved in the increased stability of beta-catenin protein. Similar to beta-catenin knockdown, USP4 silenced PC14PE6/LvBr4 cells showed decreased migratory and invasive abilities. Moreover, knockdown of both USP4 and beta-catenin inhibited clonogenicity and induced mesenchymal-epithelial transition by downregulating ZEB1 in PC14PE6/LvBr4 cells. Using bioluminescence imaging, we found that knockdown of USP4 suppressed brain metastasis in vivo and significantly increased overall survival and brain metastasis-free survival. Taken together, our results indicate that USP4 is a promising therapeutic target for brain metastasis in patients with lung adenocarcinoma. PMID- 26883471 TI - ZIF-Derived Nitrogen-Doped Porous Carbons for Xe Adsorption and Separation. AB - Currently, finding high capacity adsorbents with large selectivity to capture Xe is still a great challenge. In this work, nitrogen-doped porous carbons were prepared by programmable temperature carbonization of zeolitic imidazolate framework-8 (ZIF-8) and ZIF-8/xylitol composite precursors and the resultant samples are marked as Carbon-Z and Carbon-ZX, respectively. Further adsorption measurements indicate that ZIF-derived nitrogen-doped Carbon-ZX exhibits extremely high Xe capacity of 4.42 mmol g(-1) at 298 K and 1 bar, which is higher than almost all other pristine MOFs such as CuBTC, Ni/DOBDC, MOF-5 and Al-MIL-53, and even more than three times of the matrix ZIF-8 at similar conditions. Moreover, Carbon-ZX also shows the highest Xe/N2 selectivity about ~120, which is much larger than all other reported MOFs. These remarkable features illustrate that ZIF-derived nitrogen-doped porous carbon is an excellent adsorbent for Xe adsorption and separation at room temperature. PMID- 26883472 TI - Evidence-based or arrogance-based medicine? PMID- 26883473 TI - Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs. AB - Interleukin-24 (IL-24) is a cytokine encoded by a tumor suppressor gene of the IL 10 family, also known as the melanoma differentiation associated gene-7 (Mda-7) and first discovered in human melanoma cells. Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the sensitivity of B cell lymphoma to chemotherapy agents is not yet clear. The present study investigated the effects of Mda-7/IL-24 overexpression on the sensitivity of human B cell lymphoma cells to chemotherapy, as well as its mechanism of action. The sensitivity of stable Mda-7/IL-24 overexpressing Raji and Daudi cells to cis-diamminedichloroplatinum (CDDP), epirubicin and vinblastine (VCR) were assessed by the MTS method, and the IC50 value calculated. Cell apoptosis and the intracellular accumulation of Rhodamine-123 were assayed by flow cytometry. The expression of multidrug resistance gene 1 (MDR1), B-cell specific Moloney murine leukemia virus insertion site 1 (BMI1), topoisomerase II (Topo II) and multidrug resistance-related protein 1 (MRP1) mRNA and protein were analyzed by reverse transcription quantitative polymerase chain reaction (RT qPCR) and western blotting, respectively. In addition, western blot analysis was also used to investigate the effect of Mda-7/IL-24 on activity of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells. Growth inhibition and apoptosis rates of Mda-7/IL-24 overexpressing Raji and Daudi cells were higher than those of non transfected cells and cells transfected with vector alone when treated with CDDP, epirubicin and VCR. The IC50 values of CDDP, epirubicin and VCR were lower for Mda-7/IL-24-overexpressing Raji and Daudi cells than for non-transfected cells and cells transfected with empty vector. Intracellular accumulation of Rhodamine 123 and the expression of Topo II were higher, while the levels of MDR1, BMI and MRP1 mRNA and protein were lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Furthermore, the activities of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells were suppressed. These results indicated that Mda-7/IL-24 enhanced the sensitivity of B lymphoma cells to chemotherapy agents by altering the expression of multidrug-resistance genes via downregulating GTP-RhoA-ERK signaling pathway, suggesting that treatment of B cell lymphomas with Mda-7/IL-24 could avoid MDR. PMID- 26883474 TI - Engineering long shelf life multi-layer biologically active surfaces on microfluidic devices for point of care applications. AB - Although materials and engineered surfaces are broadly utilized in creating assays and devices with wide applications in diagnostics, preservation of these immuno-functionalized surfaces on microfluidic devices remains a significant challenge to create reliable repeatable assays that would facilitate patient care in resource-constrained settings at the point-of-care (POC), where reliable electricity and refrigeration are lacking. To address this challenge, we present an innovative approach to stabilize surfaces on-chip with multiple layers of immunochemistry. The functionality of microfluidic devices using the presented method is evaluated at room temperature for up to 6-month shelf life. We integrated the preserved microfluidic devices with a lensless complementary metal oxide semiconductor (CMOS) imaging platform to count CD4(+) T cells from a drop of unprocessed whole blood targeting applications at the POC such as HIV management and monitoring. The developed immunochemistry stabilization method can potentially be applied broadly to other diagnostic immuno-assays such as viral load measurements, chemotherapy monitoring, and biomarker detection for cancer patients at the POC. PMID- 26883475 TI - Astrocyte-derived phosphatidic acid promotes dendritic branching. AB - Astrocytes play critical roles in neural circuit formation and function. Recent studies have revealed several secreted and contact-mediated signals from astrocytes which are essential for neurite outgrowth and synapse formation. However, the mechanisms underlying the regulation of dendritic branching by astrocytes remain elusive. Phospholipase D1 (PLD1), which catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline, has been implicated in the regulation of neurite outgrowth. Here we showed that knockdown of PLD1 selectively in astrocytes reduced dendritic branching of neurons in neuron-glia mixed culture. Further studies from sandwich like cocultures and astrocyte conditioned medium suggested that astrocyte PLD1 regulated dendritic branching through secreted signals. We later demonstrated that PA was the key mediator for astrocyte PLD1 to regulate dendritic branching. Moreover, PA itself was sufficient to promote dendritic branching of neurons. Lastly, we showed that PA could activate protein kinase A (PKA) in neurons and promote dendritic branching through PKA signaling. Taken together, our results demonstrate that astrocyte PLD1 and its lipid product PA are essential regulators of dendritic branching in neurons. These results may provide new insight into mechanisms underlying how astrocytes regulate dendrite growth of neurons. PMID- 26883476 TI - Considerations for estimating microbial environmental data concentrations collected from a field setting. AB - In the event of an indoor release of an environmentally persistent microbial pathogen such as Bacillus anthracis, the potential for human exposure will be considered when remedial decisions are made. Microbial site characterization and clearance sampling data collected in the field might be used to estimate exposure. However, there are many challenges associated with estimating environmental concentrations of B. anthracis or other spore-forming organisms after such an event before being able to estimate exposure. These challenges include: (1) collecting environmental field samples that are adequate for the intended purpose, (2) conducting laboratory analyses and selecting the reporting format needed for the laboratory data, and (3) analyzing and interpreting the data using appropriate statistical techniques. This paper summarizes some key challenges faced in collecting, analyzing, and interpreting microbial field data from a contaminated site. Although the paper was written with considerations for B. anthracis contamination, it may also be applicable to other bacterial agents. It explores the implications and limitations of using field data for determining environmental concentrations both before and after decontamination. Several findings were of interest. First, to date, the only validated surface/sampling device combinations are swabs and sponge-sticks on stainless steel surfaces, thus limiting availability of quantitative analytical results which could be used for statistical analysis. Second, agreement needs to be reached with the analytical laboratory on the definition of the countable range and on reporting of data below the limit of quantitation. Finally, the distribution of the microbial field data and statistical methods needed for a particular data set could vary depending on these data that were collected, and guidance is needed on appropriate statistical software for handling microbial data. Further, research is needed to develop better methods to estimate human exposure from pathogens using environmental data collected from a field setting. PMID- 26883477 TI - Maternal exposure to air pollutant PM2.5 and PM10 during pregnancy and risk of congenital heart defects. AB - Maternal exposure to ambient air pollution has increasingly been linked to congenital heart defects (CHDs). The objective of this study was to evaluate whether high levels of maternal exposure to PM2.5 and PM10 are related to increased risk of CHDs in Wuhan, China. We conducted a cohort study with a total of 105,988 live-born infants, stillbirths, and fetal deaths. The study included mothers living in the urban district of Wuhan during pregnancy over the 2-year period from 10 June 2011 to 9 June 2013. For each study participant, we assigned 1-month and 1-week averages of PM10 and PM2.5 exposure based on measurements obtained from the nearest exposure monitor to the living residence of mothers during their early pregnancy period. Logistic regression analyses were conducted to calculate the adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the association between exposure to these ambient air pollutants during early pregnancy and CHDs. We observed an increased risk of CHDs, particularly ventricular septal defect (VSD), with increasing PM2.5 exposure. Using 1-week averages, we also observed significant monotonically increasing associations between PM2.5 exposure during weeks 7-10 of pregnancy and risk of VSD, with aORs ranging from 1.11 to 1.17 (95% CI: 1.02-1.20, 1.03-1.22, 1.05-1.24, and 1.08-1.26 separately) per a 10 MUg/m(3) change in PM2.5 concentration. Our study contributes to the small body of knowledge regarding the association between in utero exposure to air pollution and CHDs, but confirmation of these associations will be needed in future studies. PMID- 26883479 TI - Thermal equation of state of Molybdenum determined from in situ synchrotron X-ray diffraction with laser-heated diamond anvil cells. AB - Here we report that the equation of state (EOS) of Mo is obtained by an integrated technique of laser-heated DAC and synchrotron X-ray diffraction. The cold compression and thermal expansion of Mo have been measured up to 80 GPa at 300 K, and 92 GPa at 3470 K, respectively. The P-V-T data have been treated with both thermodynamic and Mie-Gruneisen-Debye methods for the thermal EOS inversion. The results are self-consistent and in agreement with the static multi-anvil compression data of Litasov et al. (J. Appl. Phys. 113, 093507 (2013)) and the theoretical data of Zeng et al. (J. Phys. Chem. B 114, 298 (2010)). These high pressure and high temperature (HPHT) data with high precision firstly complement and close the gap between the resistive heating and the shock compression experiment. PMID- 26883478 TI - Lactose-Functionalized Gold Nanorods for Sensitive and Rapid Serological Diagnosis of Cancer. AB - Timely and accurate diagnosis of cancer is crucial to cancer treatment. However, serological diagnosis of cancer still faces great challenge because the conventional methodology based on the enzyme-linked immune sorbent assay (ELISA) is costly, time-consuming, and complicated, involving multiple steps. Herein, lactose-functionalized gold nanorods (Lac-GNRs) are fabricated as efficient biosensors to detect cancerous conditions based on the unique surface plasmon resonance properties of GNRs and high specificity of lactose to the galectin-1 cancer biomarker. A trace concentration of galectin-1 as small as 10(-13) M can be detected by Lac-GNRs. The comparative study among BSA, galectin-3, and galectin-1 demonstrates the good specificity of Lac-GNRs to galectin-1 either in aqueous solutions or in the complex and heterogeneous serum specimens. Clinical tests show that the Lac-GNRs biosensors can readily distinguish the serums of cancer patients from those of healthy persons simply by using a microplate reader or even direct visual observation. The Lac-GNRs biosensing platform is highly efficient and easy to use and have great potential in rapid screening of cancer patients. PMID- 26883480 TI - More Chemistry Is Needed for Molecular Imaging. PMID- 26883482 TI - How kinematic disturbance in the deformed rheumatoid thumb impacts on hand function: a biomechanical and functional perspective. AB - Purpose This study investigates the effects of kinematic disturbances in rheumatoid thumb on patient's hand functions via objective and patient-perceived measurements. Method Twenty-one patients with rheumatoid arthritis (RA) and 21 healthy age- and gender-matched individuals were recruited to receive the objective evaluations, including the Purdue Pegboard Test, Jamar dynamometer, pinch-meter, Permanent Impairment Scale and self-administrated measurements, including the Health Assessment Questionnaire (HAQ) and Manual Ability Measure-36 (MAM-36). An electromagnetic tracking system was used to measure thumb kinematics. The differences in the measures between the RA and control groups and the dominant and non-dominant hands of the RA group were examined. The relationships between the thumb kinematics and hand functional capabilities, as well as impairment levels, were also explored. Results The RA group showed significantly smaller thumb movement capabilities and hand strength, as well as worse scores in hand dexterity, MAM-36 and HAQ than healthy controls. The movement workspace of the RA thumb showed moderate correlations with the factors of hand strength, dexterity, impairment scale, MAM-36 and HAQ scores. Conclusions The findings indicate deficits related to the movement capability of the RA thumb may negatively influence hand dexterity and functional hand performance, as well as life quality, for the patients with RA. Implications for Rehabilitation A deformed rheumatoid thumb might limit the movement workspace of the thumb and consequently impair the hand performance as well as the life quality. The dominant thumb of the RA patients might have greater structural and functional deterioration than the non-dominant side. Suitable joint protection strategies, exercises and orthotics should be early applied to the RA patients for preserving hand functions. PMID- 26883481 TI - The TRPM1 channel in ON-bipolar cells is gated by both the alpha and the betagamma subunits of the G-protein Go. AB - Transmission from photoreceptors to ON bipolar cells in mammalian retina is mediated by a sign-inverting cascade. Upon binding glutamate, the metabotropic glutamate receptor mGluR6 activates the heterotrimeric G-protein Galphaobeta3gamma13, and this leads to closure of the TRPM1 channel (melastatin). TRPM1 is thought to be constitutively open, but the mechanism that leads to its closure is unclear. We investigated this question in mouse rod bipolar cells by dialyzing reagents that modify the activity of either Galphao or Gbetagamma and then observing their effects on the basal holding current. After opening the TRPM1 channels with light, a constitutively active mutant of Galphao closed the channel, but wild-type Galphao did not. After closing the channels by dark adaptation, phosducin or inactive Galphao (both sequester Gbetagamma) opened the channel while the active mutant of Galphao did not. Co-immunoprecipitation showed that TRPM1 interacts with Gbeta3 and with the active and inactive forms of Galphao. Furthermore, bioluminescent energy transfer assays indicated that while Galphao interacts with both the N- and the C- termini of TRPM1, Gbetagamma interacts only with the N-terminus. Our physiological and biochemical results suggest that both Galphao and Gbetagamma bind TRPM1 channels and cooperate to close them. PMID- 26883483 TI - Structural modifications of the salivary conditioning film upon exposure to sodium bicarbonate: implications for oral lubrication and mouthfeel. AB - The salivary conditioning film (SCF) that forms on all surfaces in the mouth plays a key role in lubricating the oral cavity. As this film acts as an interface between tongue, enamel and oral mucosa, it is likely that any perturbations to its structure could potentially lead to a change in mouthfeel perception. This is often experienced after exposure to oral hygiene products. For example, consumers that use dentifrice that contain a high concentration of sodium bicarbonate (SB) often report a clean mouth feel after use; an attribute that is clearly desirable for oral hygiene products. However, the mechanisms by which SB interacts with the SCF to alter lubrication in the mouth is unknown. Therefore, saliva and the SCF was exposed to high ionic strength and alkaline solutions to elucidate whether the interactions observed were a direct result of SB, its high alkalinity or its ionic strength. Characteristics including bulk viscosity of saliva and the viscoelasticity of the interfacial salivary films that form at both the air/saliva and hydroxyapatite/saliva interfaces were tested. It was hypothesised that SB interacts with the SCF in two ways. Firstly, the ionic strength of SB shields electrostatic charges of salivary proteins, thus preventing protein crosslinking within the film and secondly; the alkaline pH (~8.3) of SB reduces the gel-like structure of mucins present in the pellicle by disrupting disulphide bridging of the mucins via the ionization of their cysteine's thiol group, which has an isoelectric point of ~8.3. PMID- 26883485 TI - Aflatoxins in composite spices collected from local markets of Karachi, Pakistan. AB - This survey was carried out to evaluate the occurrence of total aflatoxins (AFs; B1+B2+G1+G2) in unpacked composite spices. A total of 75 samples of composite spices such as biryani, karhai, tikka, nihari and korma masalas were collected from local markets of Karachi, Pakistan, and analysed using HPLC technique. The results indicated that AFs were detected in 77% (n = 58) samples ranging from 0.68 to 25.74 ug kg(-1) with a mean of 4.63 +/- 0.95 ug kg(-1). In 88% (n = 66) samples, AFs level was below the maximum limits (ML = 10 ug kg(-1)) as imposed by EU. Furthermore, 61% (n = 46) tested samples contained AFs level between 1 and 10 ug kg(-1), 9% (n = 7) exhibited AFs contamination ranged 10-20 ug kg(-1) and only 3% (n = 2) of the investigated samples contained AFs levels higher than the ML of 20 ug kg(-1) for total aflatoxins as set by the USA. It was concluded that there is need to establish a strict and continuous national monitoring plan to improve safety and quality of spices in Pakistan. PMID- 26883484 TI - Stigma, marginalization and psychosocial well-being of orphans in Rwanda: exploring the mediation role of social support. AB - Stigma and marginalization are one of the major challenges orphans face in their daily lives, particularly in developing countries, but little is known about their impacts on mental health. This study examines how orphan-related characteristics, stigma and marginalization are associated with psychosocial well being. It further analyses the role of social support in mediating between stigma and marginalization and mental health, indicated by emotional well-being and mental distress. The participants in this study were 430 Rwandan orphans who were 10-25 years of age, and of whom 179 were females and 251 were males. Results showed that high levels of stigma and marginalization were associated with a lower level of emotional well-being and higher levels of mental distress. A mediation analysis indicated that low level of social support due to stigma and marginalization contributed significantly to low level of emotional well-being. Once stigma, marginalization and social support were fully accounted for, AIDS orphans exhibited higher levels of mental distress than those who were orphaned by genocide or other causes. Future interventions designed to reduce stigma and marginalization for orphans and actions that facilitate social support can significantly improve emotional well-being and reduce mental distress among orphans. PMID- 26883486 TI - Beyond accuracy: creating interoperable and scalable text-mining web services. AB - The biomedical literature is a knowledge-rich resource and an important foundation for future research. With over 24 million articles in PubMed and an increasing growth rate, research in automated text processing is becoming increasingly important. We report here our recently developed web-based text mining services for biomedical concept recognition and normalization. Unlike most text-mining software tools, our web services integrate several state-of-the-art entity tagging systems (DNorm, GNormPlus, SR4GN, tmChem and tmVar) and offer a batch-processing mode able to process arbitrary text input (e.g. scholarly publications, patents and medical records) in multiple formats (e.g. BioC). We support multiple standards to make our service interoperable and allow simpler integration with other text-processing pipelines. To maximize scalability, we have preprocessed all PubMed articles, and use a computer cluster for processing large requests of arbitrary text. AVAILABILITY AND IMPLEMENTATION: Our text mining web service is freely available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmTools/#curl CONTACT: : Zhiyong.Lu@nih.gov. PMID- 26883488 TI - Identification of Novel Virulence-Associated Proteins Secreted to Xylem by Verticillium nonalfalfae During Colonization of Hop Plants. AB - Plant pathogens employ various secreted proteins to suppress host immunity for their successful host colonization. Identification and characterization of pathogen-secreted proteins can contribute to an understanding of the pathogenicity mechanism and help in disease control. We used proteomics to search for proteins secreted to xylem by the vascular pathogen Verticillium nonalfalfae during colonization of hop plants. Three highly abundant fungal proteins were identified: two enzymes, alpha-N-arabinofuranosidase (VnaAbf4.216) and peroxidase (VnaPRX1.1277), and one small secreted hypothetical protein (VnaSSP4.2). These are the first secreted proteins so far identified in xylem sap following infection with Verticillium spp. VnaPRX1.1277, classified as a heme-containing peroxidase from Class II, similar to other Verticillium spp. lignin-degrading peroxidases, and VnaSSP4.2, a 14-kDa cysteine-containing protein with unknown function and with a close homolog in related V. alfalfae strains, were further examined. The in planta expression of VnaPRX1.1277 and VnaSSP4.2 genes increased with the progression of colonization, implicating their role in fungal virulence. Indeed, V. nonalfalfae deletion mutants of both genes exhibited attenuated virulence on hop plants, which returned to the level of the wild-type pathogenicity in the knockout complementation lines, supporting VnaPRX1.1277 and VnaSSP4.2 as virulence factors required to promote V. nonalfalfae colonization of hop plants. PMID- 26883487 TI - Computationally expanding infinium HumanMethylation450 BeadChip array data to reveal distinct DNA methylation patterns of rheumatoid arthritis. AB - MOTIVATION: DNA methylation signatures in rheumatoid arthritis (RA) have been identified in fibroblast-like synoviocytes (FLS) with Illumina HumanMethylation450 array. Since <2% of CpG sites are covered by the Illumina 450K array and whole genome bisulfite sequencing is still too expensive for many samples, computationally predicting DNA methylation levels based on 450K data would be valuable to discover more RA-related genes. RESULTS: We developed a computational model that is trained on 14 tissues with both whole genome bisulfite sequencing and 450K array data. This model integrates information derived from the similarity of local methylation pattern between tissues, the methylation information of flanking CpG sites and the methylation tendency of flanking DNA sequences. The predicted and measured methylation values were highly correlated with a Pearson correlation coefficient of 0.9 in leave-one-tissue-out cross-validations. Importantly, the majority (76%) of the top 10% differentially methylated loci among the 14 tissues was correctly detected using the predicted methylation values. Applying this model to 450K data of RA, osteoarthritis and normal FLS, we successfully expanded the coverage of CpG sites 18.5-fold and accounts for about 30% of all the CpGs in the human genome. By integrative omics study, we identified genes and pathways tightly related to RA pathogenesis, among which 12 genes were supported by triple evidences, including 6 genes already known to perform specific roles in RA and 6 genes as new potential therapeutic targets. AVAILABILITY AND IMPLEMENTATION: The source code, required data for prediction, and demo data for test are freely available at: http://wanglab.ucsd.edu/star/LR450K/ CONTACT: wei-wang@ucsd.edu or gfirestein@ucsd.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26883489 TI - Phytopathogen Genome Announcement: Draft Genome Sequences of 62 Pseudomonas syringae Type and Pathotype Strains. AB - Pseudomonas syringae is a diverse species-complex that includes many important crop pathogens. Here, we report the draft genomes of 62 type and pathotype strains, which provide a genomic reference for the diversity of this species complex and will contribute to the elucidation of the genomic basis of pathogenicity and host specificity. PMID- 26883490 TI - MucR Is Required for Transcriptional Activation of Conserved Ion Transporters to Support Nitrogen Fixation of Sinorhizobium fredii in Soybean Nodules. AB - To achieve effective symbiosis with legume, rhizobia should fine-tune their background regulation network in addition to activating key genes involved in nodulation (nod) and nitrogen fixation (nif). Here, we report that an ancestral zinc finger regulator, MucR1, other than its paralog, MucR2, carrying a frameshift mutation, is essential for supporting nitrogen fixation of Sinorhizobium fredii CCBAU45436 within soybean nodules. In contrast to the chromosomal mucR1, mucR2 is located on symbiosis plasmid, indicating its horizontal transfer potential. A MucR2 homolog lacking the frameshift mutation, such as the one from S. fredii NGR234, can complement phenotypic defects of the mucR1 mutant of CCBAU45436. RNA-seq analysis revealed that the MucR1 regulon of CCBAU45436 within nodules exhibits significant difference compared with that of free-living cells. MucR1 is required for active expression of transporters for phosphate, zinc, and elements essential for nitrogenase activity (iron, molybdenum, and sulfur) in nodules but is dispensable for transcription of key genes (nif/fix) involved in nitrogen fixation. Further reverse genetics suggests that S. fredii uses high-affinity transporters to meet the demand for zinc and phosphate within nodules. These findings, together with the horizontal transfer potential of the mucR homolog, imply an intriguing evolutionary role of this ancestral regulator in supporting nitrogen fixation. PMID- 26883492 TI - Identification of immunoglobulins using Chou's pseudo amino acid composition with feature selection technique. AB - Immunoglobulins, also called antibodies, are a group of cell surface proteins which are produced by the immune system in response to the presence of a foreign substance (called antigen). They play key roles in many medical, diagnostic and biotechnological applications. Correct identification of immunoglobulins is crucial to the comprehension of humoral immune function. With the avalanche of protein sequences identified in postgenomic age, it is highly desirable to develop computational methods to timely identify immunoglobulins. In view of this, we designed a predictor called "IGPred" by formulating protein sequences with the pseudo amino acid composition into which nine physiochemical properties of amino acids were incorporated. Jackknife cross-validated results showed that 96.3% of immunoglobulins and 97.5% of non-immunoglobulins can be correctly predicted, indicating that IGPred holds very high potential to become a useful tool for antibody analysis. For the convenience of most experimental scientists, a web-server for IGPred was established at http://lin.uestc.edu.cn/server/IGPred. We believe that the web-server will become a powerful tool to study immunoglobulins and to guide related experimental validations. PMID- 26883494 TI - Unusual temperature dependence of elastic constants of an ambient-temperature discotic nematic liquid crystal. AB - We report the first experimental studies on the temperature dependence of viscoelastic properties of a room temperature discotic nematic liquid crystal. The splay elastic constant is greater than the bend elastic constant and both show unusual temperature and order parameter dependence. The rotational viscosity is remarkably larger than conventional calamitic liquid crystals. We provide a simple physical explanation based on the columnar short-range order to account for the the unusual temperature dependence of the elastic constants. PMID- 26883493 TI - Recent progress in chromogenic and fluorogenic chemosensors for hypochlorous acid. AB - Due to the biological and industrial importance of hypochlorous acid, the development of optical probes for HOCl has been an active research area. Hypochlorous acid and hypochlorite can oxidize electron-rich analytes with accompanying changes in molecular sensor spectroscopic profiles. Probes for such processes may monitor HOCl levels in the environment or in an organism and via bio-labeling or bioimaging techniques. This review summarizes recent developments in the area of chromogenic and fluorogenic chemosensors for HOCl. PMID- 26883495 TI - Tuning the work function of randomly oriented ZnO nanostructures by capping with faceted Au nanostructure and oxygen defects: enhanced field emission experiments and DFT studies. AB - The lowering of the work function (Phi) can lead to a better field emission (FE) behavior at lower threshold fields. We report on enhanced FE from randomly oriented and faceted Au-capped ZnO hetero-nanostructures (HNs) having more oxygen defects. Large-area arrays of non-aligned, faceted Au-capped ZnO HNs, such as nanowires (NWs) and triangular nanoflakes (TNFs) are grown using the chemical vapor deposition (CVD) method. Enhanced FE properties from the TNF sample resulted in a turn-on field as low as 0.52 V MUm(-1) at a current density of 0.1 mA cm(-2) and a field enhancement factor (beta) as high as ~5.16 * 10(5). Under similar experimental conditions, drawing the same current density from an NW specimen needs a higher turn-on field (0.86 V MUm(-1)) and to exhibit nearly four times less field enhancement factor compared to the TNFs samples. X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL) measurements confirm the presence of more oxygen defects in the TNF samples compared to the NW samples. Kelvin probe force microscopy (KPFM) measurements show the average local work function to be 4.70 +/- 0.1 eV for the TNF sample, which is ~ 0.34 eV lower than the NW sample. Using density functional theory (DFT) calculations, the estimated Phi values are found to be 4.98 eV for ZnO(0001), 4.17 eV for Au(001)/ZnO(0001) and 3.91 eV for Au(001)/Ovac-ZnO(0001) surfaces. The DFT results are qualitatively in agreement with our experimental results. The presence of Au nanostructures on top of O-deficient and sharp-tipped TNFs results in enhanced FE performance following their reduced tunneling barrier via pinning of effective Phi. PMID- 26883497 TI - Molecular Neuroimaging in Vascular Cognitive Impairment. PMID- 26883496 TI - MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex. AB - During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the proliferation and differentiation of NPCs by repressing pericentriolar material 1 (PCM1). Specifically, overexpression of miR-128 reduced NPC proliferation but promoted NPC differentiation into neurons both in vivo and in vitro. In contrast, the reduction of endogenous miR-128 elicited the opposite effects. Overexpression of miR-128 suppressed the translation of PCM1, and knockdown of endogenous PCM1 phenocopied the observed effects of miR-128 overexpression. Furthermore, concomitant overexpression of PCM1 and miR-128 in NPCs rescued the phenotype associated with miR-128 overexpression, enhancing neurogenesis but inhibiting proliferation, both in vitro and in utero. Taken together, these results demonstrate a novel mechanism by which miR-128 regulates the proliferation and differentiation of NPCs in the developing neocortex. PMID- 26883498 TI - Time-Varying Effects of Prasugrel Versus Clopidogrel on the Long-Term Risks of Stroke After Acute Coronary Syndromes: Results From the TRILOGY ACS Trial. AB - BACKGROUND AND PURPOSE: The role of more intense, sustained platelet inhibition in preventing stroke after acute coronary syndrome (ACS) is unclear. We observed a signal for reduced stroke risk in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial after 12 months of treatment with prasugrel versus clopidogrel in medically managed patients with ACS. METHODS: We examined 7243 patients with ACS, aged <75 years and without prior stroke, analyzing differences in baseline characteristics between patients with and without a stroke event through 30 months with a Cox proportional hazards model. We also assessed the effect of prasugrel versus clopidogrel (plus aspirin) on risk of all stroke events and ischemic stroke over time with an extended Cox proportional hazards model. RESULTS: Stroke events were infrequent through 30 months (ischemic stroke=62; hemorrhagic stroke=15). Patients with stroke were older, had more comorbidities, and had a higher Global Registry of Acute Coronary Events (GRACE) risk score. There was a trend for a lower unadjusted frequency of all stroke events through 30 months for prasugrel versus clopidogrel: 31 (1.5%) versus 46 (2.2%); P=0.08. There was a significant treatment-by-time interaction for those with ischemic stroke (P=0.03), consistent with the 12-month landmarked Kaplan-Meier log-rank test showing a reduced hazard of ischemic stroke after 12 months with prasugrel (P=0.04). No significant interactions between treatment effect of prasugrel versus clopidogrel and time were observed for all stroke events. CONCLUSIONS: We observed a potential late treatment effect for prasugrel versus clopidogrel for a reduced risk of ischemic stroke in medically managed patients with ACS aged <75 years. These hypothesis generating findings suggest that longer duration and more potent platelet inhibition with prasugrel may be associated with lower risk of ischemic stroke after 12 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998. PMID- 26883499 TI - Effect of Anticoagulation on Hospitalization Costs After Intracranial Hemorrhage in Atrial Fibrillation: A Registry Study. AB - BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is the most feared adverse event with oral anticoagulant therapy in patients with atrial fibrillation. The health economic aspects of resuming oral anticoagulant therapy after ICH are unknown. The aim was to estimate hospitalization costs of thromboembolism and hemorrhage subsequent to ICH in 2 patient groups with atrial fibrillation surviving the first 90 days post ICH: (1) patients resuming warfarin therapy within 90 days post ICH and (2) patients discontinuing therapy. METHODS: Retrospective data from Danish national registries were linked to identify patients with atrial fibrillation who suffered an ICH between January 1, 1997, and April 1, 2011. Study start was 90 days after incident ICH. Mortality was evaluated using the Kaplan-Meier estimate. Occurrence of hospitalization requiring thromboembolism and hemorrhage was used to estimate hospitalization costs by linkage of International Classification of Diseases, Tenth Revision, codes to Danish Diagnosis-Related Group tariffs. The effect of resuming warfarin therapy on average 3-year hospitalization costs was estimated by regression analysis adjusted for between-group differences in baseline characteristics. RESULTS: In the inclusion period, 2162 patients had an ICH; 1098 survived the first 90 days and were included for analysis, and of those, 267 resumed warfarin therapy. Therapy resumption reduced the mean 3-year hospitalization cost of hospitalized patients significantly by US$ 1588 (95% confidence interval, -2925 to -251) and was significantly correlated with fewer hospitalization days per hospitalized patient (-4.6 [95% confidence interval, -7.6 to -1.6]). The marginal effect of therapy resumption on hospitalization costs per patient was US$ -407 (95% confidence interval, -815 to 2). CONCLUSIONS: Resuming warfarin therapy within 90 days after ICH in patients with atrial fibrillation is associated with a decrease in average hospitalization costs. PMID- 26883500 TI - Anxiety and the Risk of Stroke: The Rotterdam Study. AB - BACKGROUND AND PURPOSE: It is unclear whether anxiety is a risk factor for stroke. We assessed the association between anxiety and the risk of incident stroke. METHODS: This population-based cohort study was based on 2 rounds of the Rotterdam Study. Each round was taken separately as baseline. In 1993 to 1995, anxiety symptoms were measured using the Hospital Anxiety and Depression Scale Anxiety (HADS-A). In 2002 to 2004, anxiety disorders were assessed using the Munich version of the Composite International Diagnostic Interview. Participants were followed up for incident stroke until January 2012. RESULTS: In the sample undergoing HADS-A (N=2625; mean age at baseline, 68.4 years), 332 strokes occurred during 32 720 years of follow-up. HADS-A score was not associated with the risk of stroke during complete follow-up (adjusted hazard ratio, 1.02; 95% confidence interval, 0.74-1.43; for HADS-A>=8 compared with HADS-A <8), although we did find an increased risk after a shorter follow-up of 3 years (adjusted hazard ratio, 2.68; 95% confidence interval, 1.33-5.41). In the sample undergoing the Munich version of the Composite International Diagnostic Interview (N=8662; mean age at baseline, 66.1 years), 340 strokes occurred during 48 703 years of follow-up. Participants with any anxiety disorder had no higher risk of stroke than participants without anxiety disorder (adjusted hazard ratio, 0.95; 95% confidence interval, 0.64-1.43). We also did not observe an increased risk of stroke for the different subtypes of anxiety. CONCLUSIONS: Anxiety disorders were not associated with stroke in our general population study. Anxiety symptoms were only related to stroke in the short term, which needs further exploration. PMID- 26883502 TI - Commentary: Adolescent Marijuana Use and Mental Health Amidst a Changing Legal Climate. AB - OBJECTIVE: The purpose of this commentary was to briefly summarize the literature on the relationship between adolescent marijuana use and mental health and how policy changes surrounding marijuana decriminalization and legalization might impact this relationship. METHODS: A comprehensive literature search on adolescent marijuana use, mental health, and the impact of decriminalization and legalization was conducted. Findings are briefly summarized and discussed. RESULTS: Although there is a great deal of ambiguity regarding the causal direction of marijuana use and mental health problems, what can safely be gleaned from this body of research is that early and frequent use of marijuana during adolescence is associated with the development of more psychiatric-related problems than occasional use or nonuse. CONCLUSIONS: Until there is greater clarity in this domain, clinicians should continue to screen adolescent patients for marijuana use as well as mental health difficulties, but may need to be more thoughtful about screening among early adolescents, if in fact a shift in the age of marijuana uptake occurs amidst policy changes. PMID- 26883501 TI - Vascular Cell Senescence Contributes to Blood-Brain Barrier Breakdown. AB - BACKGROUND AND PURPOSE: Age-related changes in the cerebrovasculature, including blood-brain barrier (BBB) disruption, are emerging as potential risks for diverse neurological conditions. Because the accumulation of senescent cells in tissues is increasingly recognized as a critical step leading to age-related organ dysfunction, we evaluated whether senescent vascular cells are associated with compromised BBB integrity. METHODS: Effects of vascular cell senescence on tight junction and barrier integrity were studied using an in vitro BBB model, composed of endothelial cells, pericytes, and astrocytes. In addition, tight junction coverage in microvessels and BBB integrity in BubR1 hypomorphic (BubR1(H/H)) mice, which display senescence cell-dependent phenotypes, were examined. RESULTS: When an in vitro BBB model was constructed with senescent endothelial cells and pericytes, tight junction structure and barrier integrity (evaluated by transendothelial electric resistance and tracer efflux assay using sodium fluorescein and Evans blue-albumin were significantly impaired. Endothelial cells and pericytes from BubR1(H/H) mice had increased senescent-associated beta galactosidase activity and p16(INK4a) expression, demonstrating an exacerbation of senescence. The coverage by tight junction proteins in the cortical microvessels were reduced in BubR1(H/H) mice, consistent with a compromised BBB integrity from permeability assays. Importantly, the coverage of microvessels by end-feet of aquaporin 4-immunoreactive astrocytes was not altered in the cortex of the BubR1(H/H) mice. CONCLUSIONS: Our results indicate that accumulation of senescent vascular cells is associated with compromised BBB integrity, providing insights into the mechanism of BBB disruption related to biological aging. PMID- 26883503 TI - Natural products-prompted chemical biology: phenotypic screening and a new platform for target identification. AB - Covering: 1993 to 2016The exploitation of small molecules from natural sources, such as microbial metabolites, has contributed to the discovery of not only new drugs but also new research tools for chemical biology. My research team has discovered several novel bioactive small molecules using in vivo cell-based phenotypic screening, and has investigated their modes of action using chemical genetics and chemical genomics. This highlight focuses on our recent discoveries and chemical genetics approaches for bioactive microbial metabolites that target cancer cells, the cancer microenvironment and cell membrane signalling. In addition, the development of two new platforms, 5-sulfonyl tetrazole-based and thiourea-modified amphiphilic lipid-based probe technologies, to identify the cellular targets of these molecules is also discussed. PMID- 26883504 TI - Physical therapy aimed at self-management versus usual care physical therapy after hip arthroscopy for femoroacetabular impingement: study protocol for a randomized controlled trial. AB - BACKGROUND: Femoroacetabular impingement has been recognized as a common cause of hip pain and dysfunction, especially in athletes. Femoroacetabular impingement can now be better treated by hip arthroscopy but it is unclear what postoperative rehabilitation of hip arthroscopy should look like. Several rehabilitation protocols have been described, but none presented clinical outcome data. These protocols also differ in frequency, duration and level of supervision. We developed a rehabilitation protocol with supervised physical therapy which showed good clinical results and is considered usual care in our treatment center. However, it is unknown whether, due to the relatively young age and low complication rate of hip arthroscopy patients, rehabilitation based on self management might lead to similar results. The aims of this pilot study are (1) to determine feasibility and acceptability of the self-management intervention, (2) to obtain a preliminary estimate of the difference in effect between physical therapy aimed at self-management versus usual care physical therapy in patients who undergo hip arthroscopy for femoroacetabular impingement. METHODS/DESIGN: Thirty participants (aged 18-50 years) scheduled for hip arthroscopy will be included and randomized (after surgery) to either self-management or usual care physical therapy in this assessor-blinded randomized controlled trial. After surgery, the self-management group will perform a home-based exercise program three times a week and will receive physical therapy treatment once every 2 weeks for 14 weeks. The usual care group will receive physical therapy treatment twice a week for 14 weeks and will perform an additional home-based exercise program once a week. Assessment will occur preoperatively and at 6, 14, 26 and 52 weeks after surgery. Primary outcomes are feasibility, acceptability and preliminary effectiveness. Feasibility and acceptability will be determined by the willingness to enroll, recruitment rate, adherence to treatment, patient satisfaction, drop-out rate and adverse events. Preliminary effectiveness will be determined using the following outcomes: the International Hip Outcome Tool 33 and hip functional performance as measured with the Single Leg Squat Test 14 weeks after surgery. DISCUSSION: The results of this study will be used to help decide on the need, feasibility and acceptability of a large-scale randomized controlled trial. TRIAL REGISTRATION: This protocol was registered with the Dutch Trial Registry (NTR5168) on 8 May 2015. PMID- 26883505 TI - Protective effects of retinoid x receptors on retina pigment epithelium cells. AB - Age-related macular degeneration (AMD) is among the main pathologies leading to blindness in adults and has currently no cure or effective treatment. Selective apoptosis of retina pigment epithelial (RPE) cells results in the progressive loss of photoreceptor neurons, with the consequent gradual vision loss. Oxidative stress plays an important role in this process. We have previously determined that activation of RXRs protects rat photoreceptor neurons from oxidative stress induced apoptosis. In this study we investigated whether RXR ligands prevented apoptosis in an RPE cell line, D407 cells, exposed to hydrogen peroxide (H2O2). H2O2 induced apoptosis of D407 cells, promoting p65NFkappaB nuclear translocation, increasing Bax mRNA expression, activating caspase-3 and altering cell morphology. We show, for the first time, that HX630, a RXR pan-agonist, protected D407 cells from H2O2-induced apoptosis, preventing p65NFkappaB nuclear translocation, increasing Bclxl and PPARgamma mRNA levels and simultaneously decreasing Bax mRNA levels and caspase-3 activation. Pretreatment with a RXR antagonist blocked HX630 protection. LG100754, which binds RXRs but only activates heterodimers and is an antagonist of RXR homodimers, also had a protective effect. In addition, only agonists known to bind to RXR/PPARgamma were protective. As a whole, our results suggest that RXR activation protects RPE cells from oxidative stress-induced apoptosis and this protection might involve signaling through a heterodimeric receptor, such as RXR/PPARgamma. These data also imply that RXR agonists might provide potential pharmacological tools for treating retina degenerative diseases. PMID- 26883507 TI - Survey of Plasmodium in the golden-headed lion tamarin (Leontopithecus chrysomelas) living in urban Atlantic forest in Rio de Janeiro, Brazil. AB - BACKGROUND: Communicating the presence of potential zoonotic pathogens such as Plasmodium spp. in wild animals is important for developing both animal and human health policies. METHODS: The translocation of an exotic and invasive population of Leontopithecus chrysomelas (golden-headed lion tamarins) required the screening of these animals for specific pathogens. This studies objective was to investigate Plasmodium spp. infection in the L. chrysomelas, both to know its prevalence in these animals in the local area and to minimize the risk of pathogens being translocated to the destination site. To investigate Plasmodium spp. infection, blood samples from 268 animals were assessed for the presence of Plasmodium spp. by genus-specific PCR and stained thick and thin blood smears were examined by light microscopy. Data of human malaria infection in the studied region was also assembled from SINAN (Diseases Information System Notification Ministry of Health of Brazil). RESULTS: Results from the PCR and microscopy were all negative and suggested that no L. chrysomelas was infected with Plasmodium spp. Analysis of SINAN data showed that malaria transmission is present among the human population in the studied region. CONCLUSIONS: This study is the first to provide information on Plasmodium spp. infection in L. chrysomelas. Plasmodium spp. infection of this species is rare or absent though malaria parasites circulate in the region. In addition, there is minimal risk of translocating Plasmodium spp. infected animals to the destination site. PMID- 26883506 TI - Patterns of treatment-seeking behaviors among caregivers of febrile young children: a Ugandan multiple case study. AB - BACKGROUND: The vast majority of malaria deaths in Uganda occur in children five and under and in rural areas. This study's exploratory case study approach captured unique situations to illustrate special attributes and aspects of treatment-seeking during a malaria episode. METHODS: During August 2010, a qualitative exploratory study was conducted in seven of Butaleja District's 12 sub-counties. Multiple case study methodology consisting of loosely-structured interviews were carried out with eight caregivers of children five and under in the local dialect. Caregivers were geographically distant and not known to each other. Interviews were translated into English and transcribed the same day. Data were analyzed using content analysis. RESULTS: Of the eight cases, children recovered fully in three instances, survived but with deficits in three, and died in two. Common to all outcomes were (1) triggers to illness recognition, (2) similar treatment sequences and practices, (3) factors which influenced caregivers' treatment-seeking decisions, (4) challenges encountered while seeking care at public health facilities, (5) cost burdens associated with managing malaria, (6) life burdens resulting from negative outcomes from malaria, (7) variations in caregiver knowledge about artemisinin combination therapy, and (8) varying perspectives how malaria management could be improved. CONCLUSIONS: Despite the reality that caregivers in Butaleja District generally share similar practices, experiences and challenges, very few children ever receive treatment in accordance with the Uganda's national guidelines. To bring national practice into conformance with policy, three advances must occur: (1) All key stakeholders (those affiliated with the formal health system--public facilities and licensed private outlets, unlicensed drug vendors, and caregivers of young children) must concur on the need and the means to improve malaria management, (2) all health providers (formal and unlicensed) need to be engaged in training and certification to improve timely access to affordable treatment irrespective of a region's remoteness or low population density, and (3) future public health interventions need to improve caregivers' capacity to take the necessary actions to best manage malaria in young children. PMID- 26883508 TI - Authors' reply to Makiyama and colleagues. PMID- 26883511 TI - Near-infrared operating lamp for intraoperative molecular imaging of a mediastinal tumor. AB - BACKGROUND: Near-Infrared (NIR) intraoperative molecular imaging is a new diagnostic modality utilized during cancer surgery for the identification of tumors, metastases and lymph nodes. Surgeons typically use headlamps during an operation to increase visible light; however, these light sources are not adapted to function simultaneously with NIR molecular imaging technology. Here, we design a NIR cancelling headlamp and utilize it during surgery to assess whether intraoperative molecular imaging of mediastinal tumors is possible. METHODS: A NIR cancelling headlamp was designed and tested using NIR spectroscopy preoperatively. Next, a 46 year-old-female was referred to the thoracic surgery clinic for a 5.8 cm mediastinal mass noted on chest x-ray. Prior to surgery, she was given intravenous indocyanine green (ICG). Then, the prototype headlamp was used in conjunction with our intraoperative molecular imaging device. The tumor was imaged both in vivo and following resection prior to pathological examination. RESULTS: NIR spectroscopy confirmed NIR light excitation of the unfiltered headlamp and the absence of NIR emitted light after addition of the filter. Next, in vivo imaging confirmed fluorescence of the tumor, but also demonstrated a significant amount of NIR background fluorescence emanating from the unfiltered headlamp. During imaging with the filtered headlamp, we again demonstrated a markedly fluorescent tumor but with a reduced false positive NIR signal. Final pathology was well-differentiated thymoma with negative surgical margins. CONCLUSIONS: NIR intraoperative molecular imaging using a systemic injection of intravenous ICG was successful in localizing a thymoma. Additionally, a simple design and implementation of a NIR cancelling headlamp reduces false positive NIR fluorescence. PMID- 26883512 TI - Epidemiology of Superficial Fungal Infections in Guangdong, Southern China: A Retrospective Study from 2004 to 2014. AB - Superficial fungal infections are common worldwide; however, the distribution of pathogenic species varies among geographical areas and changes over time. This study aimed to determine the epidemiologic profile of superficial fungal infections during 2004-2014 in Guangzhou, Southern China. Data regarding the superficial mycoses from outpatients and inpatients in our hospital were recorded and analyzed. From the 3367 patients that were enrolled in the study, 3385 samples were collected from skin, hair and nail lesions. Of the 697 positive cultures, dermatophytes were the most prevalent isolates (84.36 %), followed by yeasts (14.92 %) and non-dermatophyte molds (0.72 %). Trichophyton rubrum (56.24 %) was the most common dermatophyte isolated from cases of tinea unguium (83.92 %), tinea pedis (71.19 %), tinea cruris (91.66 %), tinea corporis (91.81 %) and tinea manuum (65.00 %). Trichophyton mentagrophytes (13.35 %) and Microsporum canis (10.19 %) were the predominant species associated with cases of tinea faciei (54.55 %) and tinea capitis (54.13 %), respectively. Yeasts and molds were identified primarily from other cases of superficial fungal infections. In conclusion, when compared to previous studies in the same area, the epidemiology of superficial mycoses in Guangdong did not significantly change from 2004 to 2014. The prevalence of causative agents and the spectrum of superficial fungal infections, particularly tinea caused by dermatophyte infection, are similar to reports from several specific regions in China and Europe, whereas increasing incidences of Trichophyton mentagrophytes and Microsporum canis occurred in Guangdong, China. PMID- 26883513 TI - Detection of Multiple Budding Yeast Cells and a Partial Sequence of 43-kDa Glycoprotein Coding Gene of Paracoccidioides brasiliensis from a Case of Lacaziosis in a Female Pacific White-Sided Dolphin (Lagenorhynchus obliquidens). AB - Lacaziosis, formerly called as lobomycosis, is a zoonotic mycosis, caused by Lacazia loboi, found in humans and dolphins, and is endemic in the countries on the Atlantic Ocean, Indian Ocean and Pacific Ocean of Japanese coast. Susceptible Cetacean species include the bottlenose dolphin (Tursiops truncatus), the Indian Ocean bottlenose dolphin (T. aduncus), and the estuarine dolphin (Sotalia guianensis); however, no cases have been recorded in other Cetacean species. We diagnosed a case of Lacaziosis in a Pacific white-sided dolphin (Lagenorhynchus obliquidens) nursing in an aquarium in Japan. The dolphin was a female estimated to be more than 14 years old at the end of June 2015 and was captured in a coast of Japan Sea in 2001. Multiple, lobose, and solid granulomatous lesions with or without ulcers appeared on her jaw, back, flipper and fluke skin, in July 2014. The granulomatous skin lesions from the present case were similar to those of our previous cases. Multiple budding and chains of round yeast cells were detected in the biopsied samples. The partial sequence of 43-kDa glycoprotein coding gene confirmed by a nested PCR and sequencing, which revealed a different genotype from both Amazonian and Japanese lacaziosis in bottlenose dolphins, and was 99 % identical to those derived from Paracoccidioides brasiliensis; a sister fungal species to L. loboi. This is the first case of lacaziosis in Pacific white-sided dolphin. PMID- 26883515 TI - Clinical application of FDG-PET/CT in metastatic infections. AB - FDG-PET/CT has proven its clinical value and cost-effectiveness in diagnosing metastatic infections in patients with Gram-positive bacteremia. In identification of metastatic foci, FDG-PET/CT is useful as a screening method when localizing symptoms are absent because it provides whole-body coverage. FDG PET/CT detects early metabolic activity rather than the late anatomical changes as visualized by computed tomography and magnetic resonance imaging. FDG-PET/CT allows more precise localization of infection within a shorter time span between injection and diagnosis as compared to conventional nuclear imaging. This review focuses on the clinical application of imaging of metastatic infectious diseases, with an emphasis on FDG-PET/CT putting it in perspective with other imaging modalities. PMID- 26883514 TI - Superficial Phaeohyphomycosis Caused by Aureobasidium melanogenum Mimicking Tinea Nigra in an Immunocompetent Patient and Review of Published Reports. AB - Aureobasidium pullulans is a ubiquitous black yeast-like fungus belonging to order Dothideales. It was regarded as a contaminant, but is now considered a pathogen causing a wide range of human infections. We report a case of superficial phaeohyphomycosis in an immunocompetent patient with clinical presentations mimicking tinea nigra. On microscopic examination of lesion scales, multiple thick-walled, pigmented oval spores with septa were noted. A fungus with black mucoid colonies was repeatedly isolated from the lesions during the treatment course. This fungus was identified as A. melanogenum on the basis of morphological characteristics and subsequently confirmed by sequencing internal transcribed spacers of ribosomal DNA. The clinical presentations and microscopic findings of lesion scales were considerably similar to those of tinea nigra. However, fungal culturing proved that the causative pathogen was A. melanogenum rather than Hortaea werneckii. The patient might have acquired this infection during gardening activities. We also reviewed reported cases of cutaneous A. pullulans infection. PMID- 26883516 TI - Half-time bone scintigraphy in prostate and breast cancer patients. AB - BACKGROUND: Developments in image reconstruction techniques for planar imaging, also known as enhanced planar processing (EPP), enable the possibility to reconstruct planar scintigraphic images with low count statistics, providing the opportunity to reduce image acquisition time. In this study, the performance of EPP for oncologic half-time bone scintigraphy images was evaluated. METHODS: The EPP software was evaluated for different imaging conditions using standardized phantom experiments. Additionally, 51 patients with prostate and breast cancer were prospectively included and underwent bone scintigraphy using a standard and half-time protocol. Independent reading was performed on three image types (standard, half-time non-processed, and half-time EPP) by three observers, scoring the number and anatomical location of lesions, image quality, and diagnostic confidence by which the definitive diagnosis was made. RESULTS: EPP images had improved contrast and lower noise levels compared to the non-processed half-time images. It was determined that EPP images acquired at double scan speed had similar image quality to the standard non-processed images. There was substantial agreement with respect to diagnosis and diagnostic confidence based on all three image types between the observers. Image quality in the EPP images was higher with respect to the non-processed half-time images, and was comparable to the standard images. CONCLUSIONS: Diagnostic confidence was not affected by reduction in image acquisition time. There was substantial agreement between all three observers with respect to the diagnosis provided in all three image types. Subjective and objective image quality improved when half-time images were processed with EPP software. PMID- 26883517 TI - Morphine Suppresses T helper Lymphocyte Differentiation to Th1 Type Through PI3K/AKT Pathway. AB - To investigate the effect of morphine on T helper lymphocyte differentiation and PI3K/AKT pathway mechanism, CD4+ lymphocytes were treated by phorbol-myristate acetate (25 ng/ml) (PMA) plus ionomycin (1 MUg/ml) in the presence of various concentrations of morphine (25, 50, 100, 200 ng/ml) for 4 h. Th1 and Th2 subsets, supernatant cytokines, and PI3K, AKT, and protein kinase C-theta (PKC-theta) levels were detected. The Th1 cell percentage, Th1-derived cytokines, and ratio of Th1/Th2 decreased in the presence of morphine in a concentration-dependent manner. However, Th2 cell percentage kept stable after morphine treatment. The phosphorylation of PI3K and AKT decreased, but the phosphorylation of PKC-theta did not change in the presence of morphine. The decreased percentage of Th1 cells and ratio of Th1/Th2 was recovered by naloxone concentration-dependently. Morphine can inhibit the differentiation of Th1 lymphocytes and decrease the ratio of Th1/Th2 via the pathway of PI3K/AKT. The effect can be inhibited by naloxone. PMID- 26883518 TI - Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury. AB - Preventing demyelination and promoting remyelination of denuded axons are promising therapeutic strategies for spinal cord injury (SCI). Epidermal growth factor receptor (EGFR) inhibition was reported to benefit the neural functional recovery and the axon regeneration after SCI. However, its role in de- and remyelination of axons in injured spinal cord is unclear. In the present study, we evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. We found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords. We thus conclude that the therapeutic effects of EGFR inhibition after SCI involves facilitating remyelination of the injured spinal cord, increasing of oligodendrocyte precursor cells and OLs, as well as suppressing the activation of astrocytes and microglia/macrophages. PMID- 26883519 TI - The AMPAR Antagonist Perampanel Attenuates Traumatic Brain Injury Through Anti Oxidative and Anti-Inflammatory Activity. AB - Perampanel is a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, approved in over 35 countries as an adjunctive therapy for the treatment of seizures. Recently, it was found to exert protective effects against ischemic neuronal injury in vitro. In the present study, we investigated the potential protective effects of perampanel in a traumatic brain injury (TBI) model in rats. Oral administration with perampanel at a dose of 5 mg/kg exerted no major organ-related toxicities. We found that perampanel significantly attenuated TBI-induced brain edema, brain contusion volume, and gross motor dysfunction. The results of Morris water maze test demonstrated that perampanel treatment also improved cognitive function after TBI. These neuroprotective effects were accompanied by reduced neuronal apoptosis, as evidenced by decreased TUNEL-positive cells in brain sections. Moreover, perampanel markedly inhibited lipid peroxidation and obviously preserved the endogenous antioxidant system after TBI. In addition, enzyme-linked immunosorbent assay (ELISA) was performed at 4 and 24 h after TBI to evaluate the expression of inflammatory cytokines. The results showed that perampanel suppressed the expression of pro-inflammatory cytokines TNF-alpha and IL-1beta, whereas increased the levels of anti-inflammatory cytokines IL-10 and TGF-beta1. These data show that the orally active AMPAR antagonist perampanel affords protection against TBI-induced neuronal damage and neurological dysfunction through anti oxidative and anti-inflammatory activity. PMID- 26883520 TI - CX3CR1 ablation ameliorates motor and respiratory dysfunctions and improves survival of a Rett syndrome mouse model. AB - Rett syndrome (RTT) is a neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding MeCP2, an epigenetic modulator that binds the methyl CpG dinucleotide in target genes to regulate transcription. Previously we and others reported a role of microglia in the pathophysiology of RTT. Because microglia in the Mecp2 knockout (Mecp2KO) mouse model of RTT over-produce neurotoxic mediators glutamate and reactive oxygen species, we hypothesize that blocking neuron-microglia interaction by ablation of CX3CR1, a chemokine receptor expressed in microglia/myeloid cells mediating such interaction by pairing with its neuronal ligand CX3CL1, would ameliorate the RTT-like phenotype in Mecp2KO mice. Here we report that CX3CR1 ablation prolonged the lifespan of Mecp2KO mice from a median survival of 54.5-74days, and significantly improved the body weight gain, symptomatic scores, major respiratory parameters, and motor coordination and performance. CX3CR1 ablation rectified previously identified histological abnormalities in the Mecp2KO brain such as neuronal soma size in hippocampal CA2, and the number, soma size, and process complexity of microglia. Moreover, CX3CR1 ablation enhanced the neurotrophic action of microglia in Mecp2KO mice by producing higher amount of insulin-like growth factor 1. Our data support a role of myeloid cells/microglia in RTT and suggest a novel therapeutic approach for RTT by targeting CX3CR1 with specific antagonists or genetic downregulation. PMID- 26883521 TI - Subtypes of depressive symptoms and inflammatory biomarkers: An exploratory study on a sample of HIV-positive patients. AB - Depressive symptoms cause major impairment and may accelerate HIV progression despite the use of antiretroviral medication. The somatic symptoms criteria for HIV infection and depression partially overlap, which can make differential diagnosis challenging. Because of chronic inflammation caused by HIV infection, HIV-positive patients may develop somatic and affective-cognitive symptoms of depression. Inflammation-related depression is primarily characterized with severe somatic symptoms such as fatigue and sleep disturbance. This study sought to explore the patterns of somatic and cognitive-affective depressive symptoms that characterize HIV-positive patients. Our specific aims were (1) to identify subtypes of depressive symptoms in a sample of HIV-positive patients; and (2) to test the subtypes' difference on inflammatory and HIV disease progression biomarkers. HIV-positive men and women (N=102) with and without depressive symptoms were randomly selected from an Italian HIV clinic. Depressive symptoms (PHQ-9), viral load (VL), CD4+, Il-6, TNF-alpha, and monocytes were assessed. The three subtypes formed using Latent Class Analysis (LCA) identified patients with (1) severe cognitive-affective and somatic depressive symptoms; (2) severe/moderate somatic symptoms; and (3) absent or low depressive symptoms. The subtype with severe/moderate somatic symptoms was characterized with elevated levels of Il-6 and monocytes. No difference on HIV progression biomarkers was found. The subtypes of depressive symptoms might help differentiating depressive symptoms from HIV- and inflammatory-related somatic symptoms. When present, cognitive-affective and/or somatic symptoms cause significant impairment to patients' lives and thus warrant further assessment and treatment. PMID- 26883522 TI - Automatic Errors: A Case Series on the Errors Inherent in Electronic Prescribing. AB - The adoption of electronic prescribing is on the rise, as it reduces medication errors compared to handwritten orders. The inadvertent dispensing of discontinued medications is a type of medication error that is less well described, but one that can lead to adverse events. Software for electronic prescriptions transmits orders for refills or new prescriptions, but not discontinuations, to the pharmacy. Medications that have been stopped are displayed only at the prescribing facility's electronic medical record (EMR). This report describes five cases in which the pharmacy dispensed electronically discontinued medications, two of which contributed to adverse outcomes. PMID- 26883523 TI - Creating the Business Case for Achieving Health Equity. AB - Health care organizations have increasingly acknowledged the presence of health care disparities across race/ethnicity and socioeconomic status, but significantly fewer have made health equity for diverse patients a true priority. Lack of financial incentives is a major barrier to achieving health equity. To create a business case for equity, governmental and private payors can: 1) Require health care organizations to report clinical performance data stratified by race, ethnicity, and socioeconomic status. 2) Incentivize preventive care and primary care. Implement more aggressive shared savings plans, update physician relative value unit fee schedules, and encourage partnerships across clinical and non-clinical sectors. 3) Incentivize the reduction of health disparities with equity accountability measures in payment programs. 4) Align equity accountability measures across public and private payors. 5) Assist safety-net organizations. Provide adequate Medicaid reimbursement, risk-adjust clinical performance scores for sociodemographic characteristics of patients, provide support for quality improvement efforts, and calibrate cuts to Disproportionate Share Hospital (DSH) payments to the pace of health insurance expansion. 6) Conduct demonstration projects to test payment and delivery system reform interventions to reduce disparities. Commitment to social justice is essential to achieve health equity, but insufficient without a strong business case that makes interventions financially feasible. PMID- 26883525 TI - Capsule Commentary on Gaither et al., The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality. PMID- 26883524 TI - Variations in Patients' Perceptions and Use of Generic Drugs: Results of a National Survey. AB - BACKGROUND: Over 84 % of all prescriptions in the US are filled as generic drugs, though in prior surveys, patients reported concerns about their quality. OBJECTIVE: We aimed to survey patients' perceptions and use of generic drugs. DESIGN: Our survey (administered August 2014) assessed patients' skepticism about generic drug safety and effectiveness and how often they requested brand-name drugs. Chi-square tests and two-sample t-tests assessed associations between patient demographics and the outcomes. PARTICIPANTS: Our sample frame was the CVS Advisor Panel, a national database of 124,621 CVS customers. We randomly selected 1450 patients with self-reported chronic conditions who filled at least one prescription in the prior 3 months. MAIN MEASURES: We assessed how often patients reported asking their physicians to prescribe a brand-name over a generic drug in the last year, and "generic skepticism," defined as not believing generic drugs were as safe, effective, had the same side effects, and contained the same active ingredients as brand-name drugs. KEY RESULTS: Of the 1,442 patients with valid addresses, 933 responded (65 % response rate) and 753 took the full survey. A vast majority (83 %) agreed that physicians should prescribe generic drugs when available, and 54 % said they had not asked their physicians to prescribe a brand name drug over a generic in the past year. Most respondents considered generic drugs to be as effective (87 %) and safe (88 %) as their brand-name counterparts, and to have the same side effects (80 %) and active ingredients (84 %). Non Caucasians were more likely than Caucasians to request a brand-name drug over a generic (56 % vs. 43 %, p < 0.01), and were also more skeptical of generic drugs' clinical equivalence (43 % vs. 29 %, p < 0.01). CONCLUSIONS: We found a substantial shift towards more patients having positive views of generic drugs, but lingering negative perceptions will have to be overcome to ensure continued cost-savings and improved patient outcomes from generic drugs. PMID- 26883527 TI - Superstorm Sandy: How the New York University Psychiatry Residency Training Program Weathered the Storm. AB - OBJECTIVE: The teaching hospitals of the New York University psychiatry residency program were evacuated and then closed for a minimum of 3 months in the aftermath of Superstorm Sandy. Faculty and residents were deployed to alternate clinical sites. The authors examine the consequences of Superstorm Sandy and its implications for the New York University psychiatry residency training program. METHODS: A survey was administered to faculty and residents. RESULTS: The authors tabulated 98 surveys, for which 24 % of faculty and 84 % of residents responded. Among respondents, 61 % believed that being involved in the evacuation of the hospitals was a positive experience. During deployment, most (85 %) found being placed with peers and supervisors to be beneficial, but there were significant disruptions. CONCLUSION: Despite facing multiple challenges including closed facilities, deployment to nonaffiliated hospitals, and exhausted personal resources, the training program continued to provide accredited clinical experiences, a core curriculum, and supervision for psychiatry residents during and after Superstorm Sandy. PMID- 26883526 TI - Effect of Pharmacist Counseling Intervention on Health Care Utilization Following Hospital Discharge: A Randomized Control Trial. AB - BACKGROUND: Reduction in 30-day readmission rates following hospitalization for acute coronary syndrome (ACS) and acute decompensated heart failure (ADHF) is a national goal. OBJECTIVE: The aim of this study was to determine the effect of a tailored, pharmacist-delivered, health literacy intervention on unplanned health care utilization, including hospital readmission or emergency room (ER) visit, following discharge. DESIGN: Randomized, controlled trial with concealed allocation and blinded outcome assessors SETTING: Two tertiary care academic medical centers PARTICIPANTS: Adults hospitalized with a diagnosis of ACS and/or ADHF. INTERVENTION: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge MAIN MEASURES: The primary outcome was time to first unplanned health care event, defined as hospital readmission or an ER visit within 30 days of discharge. Pre-specified analyses were conducted to evaluate the effects of the intervention by academic site, health literacy status (inadequate versus adequate), and cognition (impaired versus not impaired). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. KEY RESULTS: A total of 851 participants enrolled in the study at Vanderbilt University Hospital (VUH) and Brigham and Women's Hospital (BWH). The primary analysis showed no statistically significant effect on time to first unplanned hospital readmission or ER visit among patients who received interventions compared to controls (aHR = 1.04, 95% CI 0.78-1.39). There was an interaction of treatment effect by site (p = 0.04 for interaction); VUH aHR = 0.77, 95% CI 0.51 1.15; BWH aHR = 1.44 (95% CI 0.95-2.12). The intervention reduced early unplanned health care utilization among patients with inadequate health literacy (aHR 0.41, 95% CI 0.17-1.00). There was no difference in treatment effect by patient cognition. CONCLUSION: A tailored, pharmacist-delivered health literacy-sensitive intervention did not reduce post-discharge unplanned health care utilization overall. The intervention was effective among patients with inadequate health literacy, suggesting that targeted practice of pharmacist intervention in this population may be advantageous. PMID- 26883528 TI - Attitudes of Brazilian Medical Students Towards Psychiatric Patients and Mental Illness: A Quantitative Study Before and After Completing the Psychiatric Clerkship. AB - OBJECTIVE: The authors evaluated whether a psychiatric clerkship reduces stigmatized attitudes towards people with mental illness among medical students. METHODS: A 56-item questionnaire was used to assess the attitudes of medical students towards patients with mental illness and their beliefs about its causes before and after their participation in their psychiatric clerkship at a major medical school in Rio de Janeiro. Exploratory factor analysis identified four factors, reflecting "social acceptance of people with mental illness," "normalizing roles for people with mental illness in society," "non-belief in supernatural causes for mental illness," and "belief in bio-psychosocial causes for mental illness." Analysis of variance was used to evaluate changes in these factors before and after the clerkship. RESULTS: One significant difference was identified with a higher score on the factor representing social acceptance after as compared to before the clerkship (p = 0.0074). No significant differences were observed on the other factors. CONCLUSION: Participation in a psychiatric clerkship was associated with greater social acceptance but not with improvement on other attitudinal factors. This may reflect ceiling effects in responses before the clerkship concerning supernatural and bio-psychosocial beliefs about causes of mental illness that left little room for change. PMID- 26883529 TI - A Randomized Controlled Trial of Team-Based Learning Versus Lectures with Break Out Groups on Knowledge Retention. AB - OBJECTIVE: This goal of this study was to evaluate the efficacy of team-based learning (TBL) on knowledge retention compared to traditional lectures with small break-out group discussion (teaching as usual (TAU)) using a randomized controlled trial. METHODS: This randomized controlled trial was conducted during a daylong conference for psychiatric educators on attention-deficit hyperactivity disorder and the research literacy topic of efficacy versus effectiveness trials. Learners (n = 115) were randomized with concealed allocation to either TBL or TAU. Knowledge was measured prior to the intervention, immediately afterward, and 2 months later via multiple-choice tests. Participants were necessarily unblinded. Data enterers, data analysts, and investigators were blinded to group assignment in data analysis. Per-protocol analyses of test scores were performed using change in knowledge from baseline. The primary endpoint was test scores at 2 months. RESULTS: At baseline, there were no statistically significant differences between groups in pre-test knowledge. At immediate post-test, both TBL and TAU groups showed improved knowledge scores compared with their baseline scores. The TBL group performed better statistically on the immediate post-test than the TAU group (Cohen's d = 0.73; p < 0.001), although the differences in knowledge scores were not educationally meaningful, averaging just one additional test question correct (out of 15). On the 2-month remote post-test, there were no group differences in knowledge retention among the 42 % of participants who returned the 2-month test. CONCLUSIONS: Both TBL and TAU learners acquired new knowledge at the end of the intervention and retained knowledge over 2 months. At the end of the intervention day and after 2 months, knowledge test scores were not meaningfully different between TBL and TAU completers. In conclusion, this study failed to demonstrate the superiority of TBL over TAU on the primary outcome of knowledge retention at 2 months post-intervention. PMID- 26883530 TI - Proteolytic Digestion and TiO2 Phosphopeptide Enrichment Microreactor for Fast MS Identification of Proteins. AB - The characterization of phosphorylation state(s) of a protein is best accomplished by using isolated or enriched phosphoprotein samples or their corresponding phosphopeptides. The process is typically time-consuming as, often, a combination of analytical approaches must be used. To facilitate throughput in the study of phosphoproteins, a microreactor that enables a novel strategy for performing fast proteolytic digestion and selective phosphopeptide enrichment was developed. The microreactor was fabricated using 100 MUm i.d. fused-silica capillaries packed with 1-2 mm beds of C18 and/or TiO2 particles. Proteolytic digestion-only, phosphopeptide enrichment-only, and sequential proteolytic digestion/phosphopeptide enrichment microreactors were developed and tested with standard protein mixtures. The protein samples were adsorbed on the C18 particles, quickly digested with a proteolytic enzyme infused over the adsorbed proteins, and further eluted onto the TiO2 microreactor for enrichment in phosphopeptides. A number of parameters were optimized to speed up the digestion and enrichments processes, including microreactor dimensions, sample concentrations, digestion time, flow rates, buffer compositions, and pH. The effective time for the steps of proteolytic digestion and enrichment was less than 5 min. For simple samples, such as standard protein mixtures, this approach provided equivalent or better results than conventional bench-top methods, in terms of both enzymatic digestion and selectivity. Analysis times and reagent costs were reduced ~10- to 15-fold. Preliminary analysis of cell extracts and recombinant proteins indicated the feasibility of integration of these microreactors in more advanced workflows amenable for handling real-world biological samples. Graphical Abstract ?. PMID- 26883531 TI - Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities. AB - We have developed a multimodal ion source design that can be configured on the fly for various analysis modes, designed for more efficient and reproducible sampling at the mass spectrometer atmospheric pressure (AP) interface in a number of different applications. This vacuum-assisted plasma ionization (VaPI) source features interchangeable transmission mode and laser ablation sampling geometries. Operating in both AC and DC power regimes with similar results, the ion source was optimized for parameters including helium flow rate and gas temperature using transmission mode to analyze volatile standards and drug tablets. Using laser ablation, matrix effects were studied, and the source was used to monitor the products of model prebiotic synthetic reactions. PMID- 26883532 TI - Hybrid Organic/Inorganic Materials Depth Profiling Using Low Energy Cesium Ions. AB - The structures developed in organic electronics, such as organic light emitting diodes (OLEDs) or organic photovoltaics (OPVs) devices always involve hybrid interfaces, joining metal or oxide layers with organic layers. No satisfactory method to probe these hybrid interfaces physical chemistry currently exists. One promising way to analyze such interfaces is to use in situ ion beam etching, but this requires ion beams able to depth profile both inorganic and organic layers. Mono- or diatomic ion beams commonly used to depth profile inorganic materials usually perform badly on organics, while cluster ion beams perform excellently on organics but yield poor results when organics and inorganics are mixed. Conversely, low energy Cs(+) beams (<500 eV) allow organic and inorganic materials depth profiling with comparable erosion rates. This paper shows a successful depth profiling of a model hybrid system made of metallic (Au, Cr) and organic (tyrosine) layers, sputtered with 500 eV Cs(+) ions. Tyrosine layers capped with metallic overlayers are depth profiled easily, with high intensities for the characteristic molecular ions and other specific fragments. Metallic Au or Cr atoms are recoiled into the organic layer where they cause some damage near the hybrid interface as well as changes in the erosion rate. However, these recoil implanted metallic atoms do not appear to severely degrade the depth profile overall quality. This first successful hybrid depth profiling report opens new possibilities for the study of OLEDs, organic solar cells, or other hybrid devices. PMID- 26883534 TI - The Japanese Breast Cancer Society Clinical Practice Guideline for radiation treatment of breast cancer, 2015 edition. PMID- 26883535 TI - Multidisciplinary studies of the diversity and evolution in river-weeds. AB - The moss-like river-weeds or Podostemaceae offer a special opportunity to study the diversity and evolution of plants that are adapted to extreme environments. This paper reviews multidisciplinary studies on this subject. Based on field work in the four continents, we discovered many species and several genera that are new components of biodiversity, and revealed the Podostemaceae floras of East Asia, Southeast Asia, and Australia. The historical biogeography of the family, i.e., the change in distribution in space and time, is characterized by a few dispersals between continents, followed by diversification within each continent. Local species may be derived from parts of separated populations of parental species, which consequently are paraphyletic. The remarkable morphological adaptations of Podostemaceae include the development of the horizontal axis in plant body, with which the plants adhere to rock surfaces under violent current. The vertical axis is reduced or lost and the horizontal axis develops in the embryo and seedling. We also found saltational organ-level variation, such as presence or absence of shoot, shoot apical meristem, root, and root cap; the form of shoot and root; the mode of root branching and leaf production; and the number of cotyledons. Morphological evolution may not be always adaptive to the habitats, which are rocks periodically submerged across the distribution range. Analyses of shoot regulatory gene expression found that, in contrast to the expression pattern in primitive species with ordinary shoots, which is comparable with Arabidopsis, the unique pattern in derived species may result in 'fuzzy' morphology of the shoot and leaf. Finally, problems for future study are pointed out. PMID- 26883533 TI - Pitfalls of haplotype phasing from amplicon-based long-read sequencing. AB - The long-read sequencers from Pacific Bioscience (PacBio) and Oxford Nanopore Technologies (ONT) offer the opportunity to phase mutations multiple kilobases apart directly from sequencing reads. In this study, we used long-range PCR with ONT and PacBio sequencing to phase two variants 9 kb apart in the RET gene. We also re-analysed data from a recent paper which had apparently successfully used ONT to phase clinically important haplotypes at the CYP2D6 and HLA loci. From these analyses, we demonstrate PCR-chimera formation during PCR amplification and reference alignment bias are pitfalls that need to be considered when attempting to phase variants using amplicon-based long-read sequencing technologies. These methodological pitfalls need to be avoided if the opportunities provided by long read sequencers are to be fully exploited. PMID- 26883536 TI - Ultra-fast photo-carrier relaxation in Mott insulators with short-range spin correlations. AB - Ultra-fast spectroscopy can reveal the interplay of charges with low energy degrees of freedom, which underlies the rich physics of correlated materials. As a potential glue for superconductivity, spin fluctuations in Mott insulators are of particular interest. A theoretical description of the coupled spin and charge degrees of freedom is challenging, because magnetic order is often only short lived and short-ranged. In this work we theoretically investigate how the spin charge interactions influence the relaxation of a two-dimensional Mott-Hubbard insulator after photo-excitation. We use a nonequilibrium variant of the dynamical cluster approximation, which, in contrast to single-site dynamical mean field theory, captures the effect of short-range correlations. The relaxation time is found to scale with the strength of the nearest-neighbor spin correlations, and can be 10-20 fs in the cuprates. Increasing the temperature or excitation density decreases the spin correlations and thus implies longer relaxation times. This may help to distinguish the effect of spin-fluctuations on the charge relaxation from the influence of other bosonic modes in the solid. PMID- 26883538 TI - PpsA-mediated alternative pathway to complement RNase E essentiality in Escherichia coli. AB - Escherichia coli cells require RNase E, encoded by the essential gene rne, to propagate. The growth properties on different carbon sources of E. coli cells undergoing suppression of RNase E production suggested that reduction in RNase E is associated with decreased expression of phosphoenolpyruvate synthetase (PpsA), which converts pyruvate to phosphoenolpyruvate during gluconeogenesis. Western blotting and genetic complementation confirmed the role of RNase E in PpsA expression. Adventitious ppsA overexpression from a multicopy plasmid was sufficient to restore colony formation of ?rne E. coli on minimal media containing glycerol or succinate as the sole carbon source. Complementation of ?rne by ppsA overproduction was observed during growth on solid media but was only partial, and bacteria showed slowed cell division and grew as filamentous chains. We found that restoration of colony-forming ability by ppsA complementation occurred independent of the presence of endogenous RNase G or second-site suppressors of RNase E essentiality. Our investigations demonstrate the role of phosphoryl transfer catalyzable by PpsA as a determinant of RNase E essentiality in E. coli. PMID- 26883537 TI - Neuropathic osteoarthropathy with and without superimposed osteomyelitis in patients with a diabetic foot. AB - Soft tissue and bone infection involving the foot is one of the most common long term complications of diabetes mellitus, implying a serious impairment in quality of life for patients in the advanced stages of the disease. Neuropathic osteoarthropathy often coexists and differentiating between these two entities is commonly challenging, but crucial, as the management may differ substantially. The importance of correct diagnosis cannot be understated and effective management requires a multidisciplinary approach owing to the complicated nature of therapy in such patients. A missed diagnosis has a high likelihood of major morbidity for the patient, including limb amputation, and over-diagnosis results in a great socioeconomic challenge for healthcare systems, the over-utilization of healthcare resources, and the unwise use of antibiotics. Diagnosis is largely based on clinical signs supplemented by various imaging modalities such as radiography, MR imaging, and hybrid imaging techniques such as F-18 fluorodeoxyglucose-positron emission tomography. In the interests of the management of diabetic foot complications, this review article is aimed on the one hand at providing radiologists with important clinical knowledge, and on the other hand to equip clinicians with relevant radiological semiotics. PMID- 26883539 TI - Intracorporeal reconstruction after laparoscopic pylorus-preserving gastrectomy for middle-third early gastric cancer: a hybrid technique using linear stapler and manual suturing. AB - PURPOSE: Laparoscopy-assisted pylorus-preserving gastrectomy has been increasingly reported as a treatment for early gastric cancer located in the middle third of the stomach because of its low invasiveness and preservation of pyloric function. Advantages of a totally laparoscopic approach to distal gastrectomy, including small wound size, minimal invasiveness, and safe anastomosis, have been recently reported. Here, we introduce a new procedure for intracorporeal gastro-gastrostomy combined with totally laparoscopic pylorus preserving gastrectomy (TLPPG). METHODS: The stomach is transected after sufficient lymphadenectomy with preservation of infrapyloric vessels and vagal nerves. The proximal stomach is first transected near the Demel line, and the distal side is transected 4 to 5 cm from the pyloric ring. To create end-to-end gastro-gastrostomy, the posterior wall of the anastomosis is stapled with a linear stapler and the anterior wall is made by manual suturing intracorporeally. We retrospectively assessed the postoperative surgical outcomes via medical records. The primary endpoint in the present study is safety. RESULTS: Sixteen patients underwent TLPPG with intracorporeal reconstruction. All procedures were successfully performed without any intraoperative complications. The mean operative time was 275 min, with mean blood loss of 21 g. With the exception of one patient who had gastric stasis, 15 patients were discharged uneventfully between postoperative days 8 and 11. CONCLUSIONS: Our novel hybrid technique for totally intracorporeal end-to-end anastomosis was performed safely without mini laparotomy. This technique requires prospective validation. PMID- 26883540 TI - Enteroviruses in X-Linked Agammaglobulinemia: Update on Epidemiology and Therapy. AB - X-linked agammaglobulinemia (XLA) has been associated with a broad range of infections, but enteroviral disease represents one of the most damaging infections. The risk of enteroviral infection in XLA is lower now than in the setting of intramuscular immunoglobulin or in patients without immunoglobulin replacement, but the rate of infection has not declined significantly in the era of intravenous immunoglobulin replacement. Enteroviruses can cause inflammation of nearly every organ, but in XLA, infections often manifest as dermatomyositis or chronic meningoencephalitis. Difficulty and delay in recognizing symptoms and lack of specific therapy contribute to the poor outcomes. Furthermore, cerebrospinal fluid detection of enteroviruses is not very sensitive. Reluctance to perform brain biopsies can lead to significant delays. The other feature compromising outcomes is the lack of specific therapy. High-dose peripheral and intraventricular immunoglobulin have been used, but failure is still common. New antienteroviral drugs are in development and show promise for immunodeficient patients with life-threatening infections with enterovirus. PMID- 26883541 TI - Melphalan desensitization following immediate hypersensitivity in a patient undergoing conditioning for autologous hematopoietic cell transplantation. PMID- 26883542 TI - Environmental challenge: An effective approach for diagnosis and remediation of exacerbations of hypersensitivity pneumonitis. PMID- 26883543 TI - Asthma Control and Airway Inflammation in Patients with Eosinophilic Granulomatosis with Polyangiitis. AB - BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis that occurs in patients with asthma, nasal disease, blood and tissue eosinophilia, and extrapulmonary manifestations. OBJECTIVE: The aim of our study was to assess the clinical, functional, and inflammatory status of upper and lower airways in 37 patients with EGPA, examined 6.4 +/- 4.7 years after diagnosis, when they were in partial or complete remission from systemic involvement while on treatment with low-dose oral corticosteroids as maintenance therapy. METHODS: All patients performed spirometry and were assessed for bronchial hyperreactivity, sputum eosinophilia, and fractional exhaled nitric oxide; asthma control was evaluated according to the Global Initiative for Asthma (GINA) guidelines and the Asthma Control Test. Markers of systemic disease were compared with the data available at diagnosis. Nasal involvement was evaluated by using the Sino-Nasal Outcome Test, nasal endoscopy, and nasal cytology. The impact on the quality of life was evaluated by using generic (36-item short form health survey) and organ-specific questionnaires. RESULTS: At the time of the study visit, almost all patients were receiving low-dose oral corticosteroids and immunomodulating drugs, but only 50% were being treated with inhaled corticosteroids. Although low systemic disease activity was documented in the large majority of patients, poorly controlled asthma and rhinosinusitis with eosinophilic airway inflammation were demonstrated in almost all patients. A significant correlation was found between sputum and blood eosinophilia and between fractional exhaled nitric oxide and asthma control. The 36-item short form health survey questionnaire results significantly correlated with the Sino Nasal Outcome Test but not with the Asthma Control Test. CONCLUSIONS: Systemic treatment controls systemic involvement in EGPA, but not asthma and nasal diseases, which negatively affects patients' quality of life. PMID- 26883544 TI - B-cell small lymphocytic lymphoma associated with extremely high total IgE and cutaneous vasculitis. PMID- 26883545 TI - A case of pharyngeal diphtheria in Germany, June 2015. AB - BACKGROUND: In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics. RESULTS: A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection. CONCLUSION: No secondary cases were found and the patient completely recovered. PMID- 26883547 TI - Ultrasonic treatment of glassy carbon for nanoparticle preparation. AB - Glassy carbon particles (millimetric or micrometric sizes) dispersions in water were treated by ultrasound at 20kHz, either in a cylindrical reactor, or in a "Rosette" type reactor, for various time lengths ranging from 3h to 10h. Further separations sedimentation allowed obtaining few nanoparticles of glassy carbon in the supernatant (diameter <200nm). Thought the yield of nanoparticle increased together with the sonication time at high power, it tended to be nil after sonication in the cylindrical reactor. The sonication of glassy carbon micrometric particles in water using "Rosette" instead of cylindrical reactor, allowed preparing at highest yield (1-2wt%), stable suspensions of carbon nanoparticles, easily separated from the sedimented particles. Both sediment and supernatant separated by decantation of the sonicated dispersions were characterized by laser granulometry, scanning electron microscopy, X-ray microanalysis, and Raman and infrared spectroscopies. Their multiscale organization was investigated by transmission electron microscopy as a function of the sonication time. For sonication longer than 10h, these nanoparticles from supernatant (diameter <50nm) are aggregated. Their structures are more disordered than the sediment particles showing typical nanometer-sized aromatic layer arrangement of glassy carbon, with closed mesopores (diameter ~3nm). Sonication time longer than 5h has induced not only a strong amorphization (subnanometric and disoriented aromatic layer) but also a loss of the mesoporous network nanostructure. These multi-scale organizational changes took place because of both cavitation and shocks between particles, mainly at the particle surface. The sonication in water has induced also chemical effects, leading to an increase in the oxygen content of the irradiated material together with the sonication time. PMID- 26883546 TI - Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal. AB - The distribution of genetic diversity in great ape species is likely to have been affected by patterns of dispersal and mating. This has previously been investigated by sequencing autosomal and mitochondrial DNA (mtDNA), but large scale sequence analysis of the male-specific region of the Y Chromosome (MSY) has not yet been undertaken. Here, we use the human MSY reference sequence as a basis for sequence capture and read mapping in 19 great ape males, combining the data with sequences extracted from the published whole genomes of 24 additional males to yield a total sample of 19 chimpanzees, four bonobos, 14 gorillas, and six orangutans, in which interpretable MSY sequence ranges from 2.61 to 3.80 Mb. This analysis reveals thousands of novel MSY variants and defines unbiased phylogenies. We compare these with mtDNA-based trees in the same individuals, estimating time-to-most-recent common ancestor (TMRCA) for key nodes in both cases. The two loci show high topological concordance and are consistent with accepted (sub)species definitions, but time depths differ enormously between loci and (sub)species, likely reflecting different dispersal and mating patterns. Gorillas and chimpanzees/bonobos present generally low and high MSY diversity, respectively, reflecting polygyny versus multimale-multifemale mating. However, particularly marked differences exist among chimpanzee subspecies: The western chimpanzee MSY phylogeny has a TMRCA of only 13.2 (10.8-15.8) thousand years, but that for central chimpanzees exceeds 1 million years. Cross-species comparison within a single MSY phylogeny emphasizes the low human diversity, and reveals species-specific branch length variation that may reflect differences in long term generation times. PMID- 26883548 TI - Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region. AB - The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the centre of a 25 kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. In mammals, evolution maintained this unique palindromic arrangement, suggesting that it is functionally significant. Here we report that deconstructing the palindromic IgH 3'RR strongly affects its function even when enhancers are preserved. CSR and IgH transcription appear to be poorly dependent on the 3'RR architecture and it is more or less preserved, provided 3'RR enhancers are present. By contrast, a 'palindromic effect' significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally exposes them into a functional architecture of crucial importance. PMID- 26883549 TI - Intraoperative 3D contrast-enhanced ultrasound (CEUS): a prospective study of 50 patients with brain tumours. AB - BACKGROUND: Reliable intraoperative resection control during surgery of malignant brain tumours is associated with the longer overall survival of patients. B-mode ultrasound (BUS) is a familiar intraoperative imaging application in neurosurgical procedures and supplies excellent image quality. However, due to resection-induced artefacts, its ability to distinguish between tumour borders, oedema, surrounding tissue and tumour remnants is sometimes limited. In experienced hands, this "bright rim effect" could be reduced. However, it should be determined, if contrast-enhanced ultrasound can improve this situation by providing high-quality imaging during the resection. The aim of this clinical study was to examine contrast-enhanced and three-dimensional reconstructed ultrasound (3D CEUS) in brain tumour surgery regarding the uptake of contrast agent pre- and post-tumour resection, imaging quality and in comparison with postoperative magnetic resonance imaging in different tumour entities. METHODS: Fifty patients, suffering from various brain tumours intra-axial and extra-axial, who had all undergone surgery with the support of neuronavigation in our neurosurgical department, were included in the study. Their median age was 56 years (range, 28-79). Ultrasound imaging was performed before the Dura was opened and for resection control at the end of tumour resection as defined by the neurosurgeon. A high-end ultrasound (US) device (Toshiba Aplio XG(r)) with linear and sector probes for B-mode and CEUS was used. Navigation and 3D reconstruction were performed with a LOCALITE SonoNavigator(r) and the images were transferred digitally (DVI) to the navigation system. The contrast agent consists of echoic micro-bubbles showing tumour vascularisation. The ultrasound images were compared with the corresponding postoperative MR data in order to determine the accuracy and imaging quality of the tumours and tumour remnants after resection. RESULTS: Different types of tumours were investigated. High, dynamic contrast agent uptake was observed in 19 of 21 patients (90 %) suffering from glioblastoma, while in 2 patients uptake was low and insufficient. In 52.4 % of glioblastoma and grade III astrocytoma patients CEUS led to an improved delineation in comparison to BUS and showed a high-resolution imaging quality of the tumour margins and tumour boarders. Grade II and grade III astrocytoma (n = 6) as well as metastasis (n = 18) also showed high contrast agent uptake, which led in 50 % to an improved imaging quality. In 5 of these 17 patients, intraoperative CEUS for resection control showed tumour remnants, leading to further tumour resection. Patients treated with CEUS showed no increased neurological deficits after tumour resection. No pharmacological side-effects occurred. CONCLUSIONS: Three dimensional CEUS is a reliable intraoperative imaging modality and could improve imaging quality. Ninety percent of the high-grade gliomas (HGG, glioblastoma and astrocytoma grade III) showed high contrast uptake with an improved imaging quality in more than 50 %. Gross total resection and incomplete resection of glioblastoma were adequately highlighted by 3D CEUS intraoperatively. The application of US contrast agent could be a helpful imaging tool, especially for resection control in glioblastoma surgery. PMID- 26883550 TI - Retrospective analysis of 620 cases of brain abscess in Chinese patients in a single center over a 62-year period. AB - BACKGROUND: Despite advances in laboratory diagnostics, antibiotic regimens, and neurosurgical techniques, brain abscess (BA) remains a potentially fatal infectious disease. This study analyzed clinical and epidemiological aspects of BA in Chinese patients treated at a single center during a 62-year period. METHOD: We retrospectively analyzed 620 BA patients treated at Tianjin Medical University General Hospital, Tianjin, PR China from 1952 to 2014. Because of the initiation of imaging technology use in 1992, and other specific changes, we analyzed data over three study periods: 1952-1972, 1980-1991, and 2002-2014. Information including incidence, sex, age, community distribution, BA size and location, therapeutic method, prognosis and outcome of BA patients was collected and evaluated. RESULTS: Our study included 620 BA patients. The percentage mortality significantly decreased from 22.8 % in 1952 to 6.3 % in 2014 (p < 0.001). Although the incidence of BA was higher in males than females, there was no significant change in the male/female incidence ratio over time: 2.5 in 1952 1972, 2.6 in 1980-1991, and 2.2 in 2002-2014. The cryptogenic infection incidence significantly increased over time (p < 0.001). The number of positive bacterial cultures significantly decreased over the three study periods (p < 0.01). CONCLUSIONS: The prognosis of patients with BA has gradually improved over the past 62 years in Tianjin, China. This may be because improvements in neurosurgical techniques, cranial imaging, and antimicrobial regimens have facilitated less invasive and more precise neurosurgical procedures. PMID- 26883551 TI - Transaqueductal trans-Magendie fenestration of arachnoid cyst in the posterior fossa. AB - BACKGROUND: Neuroendoscopy is currently recommended as the first choice to treat posterior fossa arachnoid cysts. It has proven to be effective, providing improved outcome, and safe, having a low complication rate. Compared to craniotomy and shunt placement, it has lower surgical morbidity, minimizing or avoiding risks of subdural fluid collections, shunt infection, malfunction, overdrainage, and dependence. Usually, rigid scopes maneuvered through a suboccipital approach are used. When symptomatic obstructive hydrocephalus develops, CSF diversion is the first aim of surgery. METHODS: In these patients, a flexible scope introduced through a frontal burr hole allows not only immediate and efficient management of hydrocephalus with endoscopic third-ventriculostomy, but in selected cases also direct cyst inspection and fenestration. Navigation of an enlarged cerebral aqueduct is actually safe when performed by experienced neurosurgeons. RESULTS: We describe the cystocisternostomy of a cisterna magna arachnoid cyst using a transaqueductal trans-Magendie approach. CONCLUSIONS: This minimally invasive technique gives the possibility of performing both endoscopic third-ventriculostomy and cyst fenestration, which alone may not be enough to efficiently treat hydrocephalus. PMID- 26883552 TI - Effect of Cast Modification on Linear Dimensional Change of Acrylic Tooth Position Following Maxillary Complete Denture Processing. AB - PURPOSE: To investigate the effect of different cast modifications on the vertical and horizontal tooth position following maxillary complete denture processing. MATERIALS AND METHODS: A total of 60 maxillary master casts were prepared and arranged in six groups (n = 10). Variation in modifications between study groups 1 through 6 were as follows: no modification, butterfly post palatal seal preparation only, butterfly post palatal seal preparation with 10 mm wide/4 mm deep box, butterfly post palatal seal preparation with 10 mm wide/4 mm deep box and four round holes, butterfly post palatal seal preparation with 20 mm wide/4 mm deep box, butterfly post dam preparation with 20 mm wide/4 mm deep box and four round holes, respectively. The boxes in the respective groups were prepared on the mid-heel area of the cast. The first group was included in the study as control. The initial master cast was indexed to standardize the measurement technique on all specimens before duplication. Maxillary denture tooth set-up was completed and indexed using laboratory putty to ensure a similar set-up on all specimens. Vertical and horizontal tooth positions were measured for the maxillary left central incisor, right and left first molars in waxed complete dentures, and following processing. The measurements were done using a digital vernier caliper with manufacturing accuracy of up to 0.01 mm. The study data were entered in a Microsoft Excel Spreadsheet. Statistical analysis was done using a paired Student t-test, ANOVA, and Tukey post hoc test set at 5% level of significance. RESULTS: The paired t-test (within groups) showed significant change in all linear tooth positions for groups 1 and 2. Groups 3 through 6 had significant change in vertical dimension only. One-way ANOVA indicated that no significant difference was seen in the vertical tooth movements between the groups; however, statistically significant reduction was seen in the horizontal tooth movements at the maxillary left central incisor, right and left first molars for groups 3 through 6 when compared to others without significant difference between them. CONCLUSIONS: Within the limitations of the study, it was concluded that the movement of the teeth horizontally could be reduced with master cast modification (box alone or box and round holes) whereas the vertical movement of the teeth was not affected by the cast modifications made across all groups. PMID- 26883553 TI - Intraoperative 5-aminolevulinic acid-mediated photodynamic diagnosis of gallbladder cancer: A case report. PMID- 26883554 TI - Effects of dietary supplementation of pioglitazone on metabolism, milk yield, and reproductive performance in transition dairy cows. AB - The objective of this study was to investigate the effect of dietary supplementation of pioglitazone (PGT), a specific ligand for PPARgamma, on metabolic dynamics, milk production, and reproductive performance of transition dairy cows. Eighty multiparous Holstein cows in their second or more lactations were blocked by the calving date and parity and assigned randomly to four dietary groups (n = 20 cow/treatment) including control (no PGT-/-), supplemented with PGT (6-mg PGT/kg body weight) from Day -14 to +21 relative to parturition (PGT+/+) or only during prepartum (PGT+/-) or postpartum periods (PGT-/+). Postpartum body condition score and body weight loss decreased (P < 0.05) in all PGT-supplemented groups. Milk yield was not affected by PGT supplementation (P > 0.05). Percentage of milk fat decreased (P < 0.05) in all PGT-treated groups; however, milk fat yield was lower (P < 0.05) in PGT (+/+) and PGT (+/-) groups compared with PGT (-/-). Peripartum (Day -7 to +7) concentrations of plasma nonesterified fatty acids and beta-Hydroxybutyrate decreased in PGT (+/+) but not in the PGT (-/-) group (P < 0.05). During the postpartum period, PGT reduced (P > 0.05) plasma concentrations of nonesterified fatty acids in all PGT-treated groups but did not affect beta-Hydroxybutyrate level. Plasma concentrations of triglycerides decreased in all PGT-supplemented groups. Supplementation of PGT increased the peripartum concentrations of plasma glucose in PGT (+/+) and PGT (+/-) groups compared with control. Plasma concentrations of insulin-like growth factor 1 were higher in PGT (+/+) compared with the control group during both the peripartum and postpartum periods. Plasma concentrations of growth hormone and insulin were not affected by PGT treatment (P > 0.05). Mean days to ovulation were lower in PGT (+/+) and PGT (-/+), and the proportion of cows ovulating by Day 14 postpartum was higher in PGT (+/+) compared with control. Days open were shorter in PGT (+/+), PGT (+/-), and PGT (-/+) groups compared with control. However, the proportion of pregnant cows at 120 days in milk were higher in all PGT-supplemented groups. The results showed positive effects of dietary supplementation of PGT, especially supplementation during both the prepartum and postpartum periods, on metabolic dynamics, ovarian function, and reproductive performance in transition dairy cows. PMID- 26883555 TI - Asymmetric Synthesis of Monofluorinated 1-Amino-1,2-dihydronaphthalene and 1,3 Amino Alcohol Derivatives. AB - Enantioenriched 1-amino-4-fluoro-1,2-dihydronaphthalene derivatives are accessed via two complementary synthetic strategies. The careful optimization of the reaction conditions required for the elimination step in one route has allowed both the identification of an anchimerically assisted reaction pathway and, more importantly, access to a divergent reaction pathway toward fluorinated 1,3-amino alcohols from a common intermediate just by adjusting the number of equivalents of base used. PMID- 26883556 TI - Crystallized phenol application and modified Limberg flap procedure in treatment of pilonidal sinus disease: A comparative retrospective study. AB - BACKGROUND/OBJECTIVE: Pilonidal sinus treatment includes various surgical and minimally invasive procedures, but there is still no standard treatment. Flap reconstructions and minimally invasive treatment options such as crystallized phenol application have recently been in the center of interest. The aim of this study is to compare crystallized phenol application as a minimally invasive treatment with modified Limberg flap reconstruction from many aspects. METHODS: Thirty-seven patients diagnosed with pilonidal sinus and treated with modified Limberg flap reconstruction, and 44 patients treated with crystallized phenol application were evaluated retrospectively in terms of age, sex, length of stay in hospital postoperatively, wound complications, and the cause and rate of recurrence. RESULTS: Length of hospital stay was decreased and no postoperative incision problems were found in the group treated with crystallized phenol application (p < 0.001 and p = 0.011, respectively). The difference between the groups in terms of recurrence rate was not statistically significant (p = 0.173). Although the recurrence rate was found to be higher in the patient group treated once with crystallized phenol application, the success rate following multiple applications of crystallized phenol was found to be 94.5%. Higher body mass index (> 24.9 kg/m(2)) and surgical site infection were strongly correlated with recurrence rate (p < 0.001). DISCUSSION: Crystallized phenol application is a good alternative to the modified Limberg flap procedure and other surgical procedures, because it has several advantages such as being a minimally invasive procedure performed under local anesthesia with higher success rate after multiple applications, decreased length of stay in hospital, and minimal scar tissue formation. PMID- 26883557 TI - Stress-induced neutral lipid biosynthesis in microalgae - Molecular, cellular and physiological insights. AB - Photosynthetic microalgae have promise as biofuel feedstock. Under certain conditions, they produce substantial amounts of neutral lipids, mainly in the form of triacylglycerols (TAGs), which can be converted to fuels. Much of our current knowledge on the genetic and molecular basis of algal neutral lipid metabolism derives mainly from studies of plants, i.e. seed tissues, and to a lesser extent from direct studies of algal lipid metabolism. Thus, the knowledge of TAG synthesis and the cellular trafficking of TAG precursors in algal cells is to a large extent based on genome predictions, and most aspects of TAG metabolism have yet to be experimentally verified. The biofuel prospects of microalgae have raised the interest in mechanistic studies of algal TAG biosynthesis in recent years and resulted in an increasing number of publications on lipid metabolism in microalgae. In this review we summarize the current findings on genetic, molecular and physiological studies of TAG accumulation in microalgae. Special emphasis is on the functional analysis of key genes involved in TAG synthesis, molecular mechanisms of regulation of TAG biosynthesis, as well as on possible mechanisms of lipid droplet formation in microalgal cells. This article is part of a Special Issue entitled: Plant Lipid Biology edited by Kent D. Chapman and Ivo Feussner. PMID- 26883558 TI - Dispensing of high concentration Ag nano-particles ink for ultra-low resistivity paper-based writing electronics. AB - Paper-based writing electronics has received a lot of interest recently due to its potential applications in flexible electronics. To obtain ultra-low resistivity paper-based writing electronics, we developed a kind of ink with high concentration of Ag Nano-particles (up to 80 wt%), as well as a related dispensing writing system consisting an air compressor machine and a dispenser. Additionally, we also demonstrated the writability and practical application of our proposed ink and writing system. Based on the study on the effect of sintering time and pressure, we found the optimal sintering time and pressure to obtain high quality Ag NPs wires. The electrical conductivity of nano-silver paper-based electronics has been tested using the calculated resistivity. After hot-pressure sintering at 120 degrees C, 25 MPa pressure for 20 minutes, the resistivity of silver NPs conductive tracks was 3.92 * 10(-8) (Omegam), only 2.45 times of bulk silver. The mechanical flexibility of nano-silver paper-based electronics also has been tested. After 1000 bending cycles, the resistivity slightly increased from the initial 4.01 * 10(-8) to 5.08 * 10(-8) (Omegam). With this proposed ink preparation and writing system, a kind of paper-based writing electronics with ultra-low resistivity and good mechanical flexibility was achieved. PMID- 26883559 TI - Improving Tumor Treating Fields Treatment Efficacy in Patients With Glioblastoma Using Personalized Array Layouts. AB - PURPOSE: To investigate tumors of different size, shape, and location and the effect of varying transducer layouts on Tumor Treating Fields (TTFields) distribution in an anisotropic model. METHODS AND MATERIALS: A realistic human head model was generated from MR images of 1 healthy subject. Four different virtual tumors were placed at separate locations. The transducer arrays were modeled to mimic the TTFields-delivering commercial device. For each tumor location, varying array layouts were tested. The finite element method was used to calculate the electric field distribution, taking into account tissue heterogeneity and anisotropy. RESULTS: In all tumors, the average electric field induced by either of the 2 perpendicular array layouts exceeded the 1-V/cm therapeutic threshold value for TTFields effectiveness. Field strength within a tumor did not correlate with its size and shape but was higher in more superficial tumors. Additionally, it always increased when the array was adapted to the tumor's location. Compared with a default layout, the largest increase in field strength was 184%, and the highest average field strength induced in a tumor was 2.21 V/cm. CONCLUSIONS: These results suggest that adapting array layouts to specific tumor locations can significantly increase field strength within the tumor. Our findings support the idea of personalized treatment planning to increase TTFields efficacy for patients with GBM. PMID- 26883560 TI - Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound. AB - PURPOSE: Local recurrence of prostate cancer after cryosurgery (CS) and high intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. METHODS AND MATERIALS: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. RESULTS: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. CONCLUSIONS: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL. PMID- 26883562 TI - Evaluation of Health Economics in Radiation Oncology: A Systematic Review. AB - PURPOSE: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time. METHODS AND MATERIALS: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005 2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time. RESULTS: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065). CONCLUSIONS: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings. PMID- 26883561 TI - Truncated Plasminogen Activator Inhibitor-1 Protein Protects From Pulmonary Fibrosis Mediated by Irradiation in a Murine Model. AB - PURPOSE: To determine whether the delivery of recombinant truncated plasminogen activator inhibitor-1 (PAI-1) protein (rPAI-1(23)) would protect from the development of radiation-induced lung injury. METHODS AND MATERIALS: C57Bl/6 mice received intraperitoneal injections of rPAI-1(23) (5.4 MUg/kg/d) or vehicle for 18 weeks, beginning 2 days before irradiation (IR) (5 daily fractions of 6 Gy). Cohorts of mice were followed for survival (n=8 per treatment) and tissue collection (n=3 per treatment and time point). Fibrosis in lung was assessed with Masson-Trichrome staining and measurement of hydroxyproline content. Senescence was assessed with staining for beta-galactosidase activity in lung and primary pneumocytes. RESULTS: Hydroxyproline content in irradiated lung was significantly reduced in mice that received rPAI-1(23) compared with mice that received vehicle (IR+vehicle: 84.97 MUg/lung; IR+rPAI-1(23): 56.2 MUg/lung, P=.001). C57Bl/6 mice exposed to IR+vehicle had dense foci of subpleural fibrosis at 19 weeks, whereas the lungs of mice exposed to IR+rPAI-1(23) were largely devoid of fibrotic foci. Cellular senescence was significantly decreased by rPAI-1(23) treatment in primary pneumocyte cultures and in lung at multiple time points after IR. CONCLUSIONS: These studies identify that rPAI-1(23) is capable of preventing radiation-induced fibrosis in murine lungs. These antifibrotic effects are associated with increased fibrin metabolism, enhanced matrix metalloproteinase-3 expression, and reduced senescence in type 2 pneumocytes. Thus, rPAI-1(23) is a novel therapeutic option for radiation-induced fibrosis. PMID- 26883563 TI - Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study. AB - PURPOSE: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). METHODS AND MATERIALS: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. RESULTS: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5 and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. CONCLUSIONS: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended. PMID- 26883564 TI - Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid Based Brachytherapy. AB - PURPOSE: To calculate vaginal doses during image guided brachytherapy with volume based metrics and correlate with long-term vaginal toxicity. METHODS AND MATERIALS: In this institutional review board-approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance-guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an alpha/beta of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. RESULTS: A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. CONCLUSIONS: Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted. PMID- 26883565 TI - Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer. AB - PURPOSE: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. METHODS AND MATERIALS: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m(2) under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions under the fixed recommended gemcitabine dose determined. RESULTS: Seventy-six patients were enrolled. Among the 72 treated patients, dose limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m(2). The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m(2)) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (>=45.6 GyE) were 35% and 48%, respectively. CONCLUSIONS: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer. PMID- 26883566 TI - Nerve growth factor alters microtubule targeting agent-induced neurotransmitter release but not MTA-induced neurite retraction in sensory neurons. AB - Peripheral neuropathy is a dose-limiting side effect of anticancer treatment with the microtubule-targeted agents (MTAs), paclitaxel and epothilone B (EpoB); however, the mechanisms by which the MTAs alter neuronal function and morphology are unknown. We previously demonstrated that paclitaxel alters neuronal sensitivity, in vitro, in the presence of nerve growth factor (NGF). Evidence in the literature suggests that NGF may modulate the neurotoxic effects of paclitaxel. Here, we examine whether NGF modulates changes in neuronal sensitivity and morphology induced by paclitaxel and EpoB. Neuronal sensitivity was assessed using the stimulated release of calcitonin gene-related peptide (CGRP), whereas morphology of established neurites was evaluated using a high content screening system. Dorsal root ganglion cultures, maintained in the absence or presence of NGF, were treated from day 7 to day 12 in culture with paclitaxel (300nM) or EpoB (30nM). Following treatment, the release of CGRP was stimulated using capsaicin or high extracellular potassium. In the presence of NGF, EpoB mimicked the effects of paclitaxel: capsaicin-stimulated release was attenuated, potassium-stimulated release was slightly enhanced and the total peptide content was unchanged. In the absence of NGF, both paclitaxel and EpoB decreased capsaicin- and potassium-stimulated release and the total peptide content, suggesting that NGF may reverse MTA-induced hyposensitivity. Paclitaxel and EpoB both decreased neurite length and branching, and this attenuation was unaffected by NGF in the growth media. These differential effects of NGF on neuronal sensitivity and morphology suggest that neurite retraction is not a causative factor to alter neuronal sensitivity. PMID- 26883567 TI - Tissue-based multiphoton analysis of actomyosin and structural responses in human trabecular meshwork. AB - The contractile trabecular meshwork (TM) modulates aqueous humor outflow resistance and intraocular pressure. The primary goal was to visualize and quantify human TM contractile state by analyzing actin polymerization (F-actin) by 2-photon excitation fluorescence imaging (TPEF) in situ. A secondary goal was to ascertain if structural extracellular matrix (ECM) configuration changed with contractility. Viable ex vivo human TM was incubated with latrunculin-A (Lat-A) or vehicle prior to Alexa-568-phalloidin labeling and TPEF. Quantitative image analysis was applied to 2-dimensional (2D) optical sections and 3D image reconstructions. After Lat-A exposure, (a) the F-actin network reorganized as aggregates; (b) F-actin-associated fluorescence intensity was reduced by 48.6% (mean; p = 0.007; n = 8); (c) F-actin 3D distribution was reduced by 68.9% (p = 0.040); (d) ECM pore cross-sectional area and volume were larger by 36% (p = 0.032) and 65% (p = 0.059) respectively and pores appeared more interconnected; (e) expression of type I collagen and elastin, key TM structural ECM proteins, were unaltered (p = 0.54); and (f) tissue viability was unchanged (p = 0.39) relative to vehicle controls. Thus Lat-A-induced reduction of actomyosin contractility was associated with TM porous expansion without evidence of reduced structural ECM protein expression or cellular viability. These important subcellular-level dynamics could be visualized and quantified within human tissue by TPEF. PMID- 26883569 TI - Linking between genetic structure and geographical distance: Study of the maternal gene pool in the Ethiopian population. AB - Background The correlation between genetics and geographical distance has already been examined through the study of the dispersion of human populations, especially in terms of uniparental genetic markers. Aim The present work characterises, at the level of the mitochondrial DNA (mtDNA), two new samples of Amhara and Oromo populations from Ethiopia to evaluate the possible pattern of distribution for mtDNA variation and to test the hypothesis of the Isolation-by Distance (IBD) model among African, European and Middle-Eastern populations. Subjects and methods This study analysed 173 individuals belonging to two ethnic groups of Ethiopia, Amhara and Oromo, by assaying HVS-I and HVS-II of mtDNA D loop and informative coding region SNPs of mtDNA. Results The analysis suggests a relationship between genetic and geographic distances, affirming that the mtDNA pool of Africa, Europe and the Middle East might be coherent with the IBD model. Moreover, the mtDNA gene pools of the Sub-Saharan African and Mediterranean populations were very different. Conclusion In this study the pattern of mtDNA distribution, beginning with the Ethiopian plateau, was tested in the IBD model. It could be affirmed that, on a continent scale, the mtDNA pool of Africa, Europe and the Middle East might fall under the IBD model. PMID- 26883568 TI - Fire blight disease reactome: RNA-seq transcriptional profile of apple host plant defense responses to Erwinia amylovora pathogen infection. AB - The molecular basis of resistance and susceptibility of host plants to fire blight, a major disease threat to pome fruit production globally, is largely unknown. RNA-sequencing data from challenged and mock-inoculated flowers were analyzed to assess the susceptible response of apple to the fire blight pathogen Erwinia amylovora. In presence of the pathogen 1,080 transcripts were differentially expressed at 48 h post inoculation. These included putative disease resistance, stress, pathogen related, general metabolic, and phytohormone related genes. Reads, mapped to regions on the apple genome where no genes were assigned, were used to identify potential novel genes and open reading frames. To identify transcripts specifically expressed in response to E. amylovora, RT-PCRs were conducted and compared to the expression patterns of the fire blight biocontrol agent Pantoea vagans strain C9-1, another apple pathogen Pseudomonas syringae pv. papulans, and mock inoculated apple flowers. This led to the identification of a peroxidase superfamily gene that was lower expressed in response to E. amylovora suggesting a potential role in the susceptibility response. Overall, this study provides the first transcriptional profile by RNA seq of the host plant during fire blight disease and insights into the response of susceptible apple plants to E. amylovora. PMID- 26883570 TI - Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder. AB - BACKGROUND: The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. METHODS: Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. RESULTS: At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. CONCLUSION: The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders. PMID- 26883571 TI - Pancreatitis associated with metformin used for management of clozapine-related weight gain. PMID- 26883572 TI - Attachment style and interpersonal trauma in refugees. AB - BACKGROUND: Refugees can suffer many experiences that threaten their trust in others. Although models of refugee mental health have postulated that attachment securities may be damaged by refugee experiences, this has yet to be empirically tested. This study aimed to understand the relationship between the nature of traumatic experiences sustained by refugees and attachment styles. METHOD: In a cross-sectional study, treatment-seeking refugees (N = 134) were assessed for traumatic exposure using the Harvard Trauma Questionnaire and Posttraumatic Diagnostic Scale. Attachment style was assessed using the Experiences in Close Relationship Scale. RESULTS: Whereas gender and severity of interpersonal traumatic events predicted avoidant attachment style (accounting for 11% of the variance), neither these factors nor non-interpersonal trauma predicted anxious attachment. CONCLUSIONS: Exposure to interpersonal traumatic events, including torture, is associated with enduring avoidant attachment tendencies in refugees. This finding accords with attachment theories that prior adverse interpersonal experiences can undermine secure attachment systems, and may promote avoidance of attachment seeking. This finding may point to an important process maintaining poor psychological health in refugees affected by interpersonal trauma. PMID- 26883573 TI - Cigarette smoke extract induces the proliferation of normal human urothelial cells through the NF-kappaB pathway. AB - Bladder cancer is a common genitourinary malignant disease worldwide. Convincing evidence shows that cigarette smoke (CS) is a crucial risk factor for bladder cancer, yet the role of the NF-kappaB signaling pathway in the development of CS associated bladder cancer has not been fully elucidated. In the present study, we found that exposure to cigarette smoke extract (CSE) induced proliferation and triggered the transition of normal human urothelial cells from G1 to S phase. Moreover, CSE exposure enhanced the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) and decreased the expression of p21 in SV-HUC-1 cells. Furthermore, the levels of nuclear NF-kappaB p65/p50 were significantly elevated by CSE. Pre-treatment with the NF-kappaB inhibitor (PDTC) reversed CSE triggered cell proliferation. Taken together, our study revealed that CSE induced proliferation of normal human urothelial cells through the NF-kappaB pathway, and these data enhance our understanding of the CSE-related carcinogenesis of bladder cancer. PMID- 26883575 TI - Gateable Skyrmion Transport via Field-induced Potential Barrier Modulation. AB - We report on the influence of pinning potentials on current-driven skyrmion dynamics and demonstrate that skyrmions can be gated via either magnetic or electric fields. When encountering pinning potentials, skyrmions are well known to simply skirt around them. However, we show that skyrmions can be depinned much more easily when their driving force is oriented against the pinning site rather that the intuitive option of being oriented away. This observation can be exploited together with the normally undesirable Magnus force for the creation of a skyrmion diode. The phenomenon is explained by the increased skyrmion compression resulting from the spin transfer torque opposing the repulsive potential. The smaller skyrmion size then experiences a reduced pinning potential. For practical low-power device applications, we show that the same skyrmion compression can be recreated by applying either a magnetic or electric field. Our analysis provides an insight on the skyrmion dynamics and manipulation that is critical for the realization of skyrmion-based transistors and low-power memory. PMID- 26883576 TI - Distribution of soil selenium in China is potentially controlled by deposition and volatilization? AB - Elucidating the environmental drivers of selenium (Se) spatial distribution in soils at a continental scale is essential to better understand it's biogeochemical cycling to improve Se transfer into diets. Through modelling Se biogeochemistry in China we found that deposition and volatilization are key factors controlling distribution in surface soil, rather than bedrock-derived Se (<0.1 mg/kg). Wet deposition associated with the East Asian summer monsoon, and dry deposition associated with the East Asian winter monsoon, are responsible for dominant Se inputs into northwest and southeast China, respectively. In Central China the rate of soil Se volatilization is similar to that of Se deposition, suggesting that Se volatilization offsets it's deposition, resulting in negligible net Se input in soil. Selenium in surface soil at Central China is roughly equal to low petrogenic Se, which is the main reason for the presence of the Se poor belt. We suggest that both deposition and volatilization of Se could play a key role in Se balance in other terrestrial environments worldwide. PMID- 26883574 TI - Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance. AB - Tamoxifen is the accepted therapy for patients with estrogen receptor-alpha (ERalpha)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentrations of tamoxifen and its metabolites, which accumulate in tumors of patients, killed both ERalpha-positive and ERalpha-negative breast cancer cells. This depended on oxidative damage and anti-oxidants rescued the cancer cells from tamoxifen-induced apoptosis. Breast cancer cells responded to tamoxifen-induced oxidation by increasing Nrf2 expression and subsequent activation of the anti-oxidant response element (ARE). This increased the transcription of anti-oxidant genes and multidrug resistance transporters. As a result, breast cancer cells are able to destroy or export toxic oxidation products leading to increased survival from tamoxifen-induced oxidative damage. These responses in cancer cells also occur in breast tumors of tamoxifen-treated mice. Additionally, high levels of expression of Nrf2, ABCC1, ABCC3 plus NAD(P)H dehydrogenase quinone-1 in breast tumors of patients at the time of diagnosis were prognostic of poor survival after tamoxifen therapy. Therefore, overcoming tamoxifen-induced activation of the ARE could increase the efficacy of tamoxifen in treating breast cancer. PMID- 26883578 TI - Ultrasensitive Bisphenol A Field-Effect Transistor Sensor Using an Aptamer Modified Multichannel Carbon Nanofiber Transducer. AB - Bisphenol A (BPA) is a known endocrine-disrupting compound (EDC) that has a structure similar to that of the hormone estrogen. Even low concentrations of BPA are able to bind estrogen receptors, thereby inducing severe diseases such as reproductive disorders, chronic diseases, and various types of cancer. Despite such serious effects, the use of BPA remains widespread. Therefore, monitoring of both dietary and nondietary exposure to BPA is important for human healthcare. Herein, we present a field-effect transistor (FET) sensor using aptamer-modified multichannel carbon nanofibers (MCNFs) to detect BPA. The MCNFs are fabricated via single-nozzle electrospinning of two immiscible polymer solutions followed by thermal treatment in an inert atmosphere. The MCNFs are then oxidized using a solution of HNO3 and H2SO4 to introduce carboxyl groups on the surface of the fibers. The carboxyl-functionalized MCNFs (CMCNFs) are immobilized on an amine functionalized electrode substrate by forming a covalent bond, and amine functionalized BPA-binding aptamers are modified in the same manner on the CMCNFs. The resulting FET sensors exhibit a high sensitivity, as well as specificity toward BPA at an unprecedentedly low concentration of 1 fM. Furthermore, these sensors are stable and could be reused for repeated assays. PMID- 26883577 TI - Intrathecal delivery of frataxin mRNA encapsulated in lipid nanoparticles to dorsal root ganglia as a potential therapeutic for Friedreich's ataxia. AB - In Friedreich's ataxia (FRDA) patients, diminished frataxin (FXN) in sensory neurons is thought to yield the predominant pathology associated with disease. In this study, we demonstrate successful usage of RNA transcript therapy (RTT) as an exogenous human FXN supplementation strategy in vitro and in vivo, specifically to dorsal root ganglia (DRG). Initially, 293 T cells were transfected with codon optimized human FXN mRNA, which was translated to yield FXN protein. Importantly, FXN was rapidly processed into the mature functional form of FXN (mFXN). Next, FXN mRNA, in the form of lipid nanoparticles (LNPs), was administered intravenously in adult mice. Examination of liver homogenates demonstrated efficient FXN LNP uptake in hepatocytes and revealed that the mitochondrial maturation machinery had efficiently processed all FXN protein to mFXN in ~24 h in vivo. Remarkably, greater than 50% mFXN protein derived from LNPs was detected seven days after intravenous administration of FXN LNPs, suggesting that the half life of mFXN in vivo exceeds one week. Moreover, when FXN LNPs were delivered by intrathecal administration, we detected recombinant human FXN protein in DRG. These observations provide the first demonstration that RTT can be used for the delivery of therapeutic mRNA to DRG. PMID- 26883579 TI - Thrombopoietin receptor is required for the oncogenic function of CALR mutants. PMID- 26883580 TI - Aflatoxins in dairy cow feed, raw milk and milk products from Turkey. AB - This study aims to detect aflatoxins (AFs) in dairy cow feed, milk and milk products using a high-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method. All the validation parameters met the method performance criteria of the European Union. The samples comprised 76 dairy cow feeds and 205 milk and milk products (including yoghurt and yoghurt-based beverage, ayran). AFs were present in 26.3% of the feed samples. Two feed samples exceeded the maximum limit (ML) of 5 ug kg(-1) for AFB1 as established by the EU. Nineteen milk samples (21.1%) contained aflatoxin M1 (AFM1) of which three exceeded the EU ML of 0.05 ug l(-1). In addition, only two yoghurt samples and one ayran sample contained AFM1, but the levels were lower than the EU ML. PMID- 26883581 TI - Same-sex sexual attraction, behavior, and practices of Jewish men in Israel and the association with HIV prevalence. AB - In order to efficiently direct efforts and resources required for the prevention of HIV and other sexually transmitted infection among men who have sex with men (MSM) in Israel, it is necessary to define their particular behaviors, estimate their size, and asses the HIV-burden. This cross-sectional study included a sub sample from a random representative National study performed in Israel, which included Jewish males aged 18-44 who completed online anonymous questionnaires regarding their sexual attraction and practices, commercial sex-work, as well as condom and substances' use. Additionally, participants were asked to identify themselves as gay, bisexual, or heterosexual. National estimates regarding prevalence of risk-behaviors and HIV-infection among MSM were based on the Statistical Abstract of Israel and the National HIV Registry, respectively. Of the total sample of 997 men, 11.9% reported lifetime male sex encounters, while 4.5% and 3.7% self-identified as gay or bisexual, respectively. The estimated population of self-identified Jewish gays/bisexuals aged 18-44 in Israel was 94,176, and in Tel-Aviv 33,839. HIV prevalence among MSM was estimated at 0.7% in Israel and 1.0% in Tel-Aviv. MSM were more likely to live in Tel-Aviv, had higher levels of education, and were scored higher on several determinants of sexual risk in comparison to those attracted to women, including early sexual debut, greater number of sexual partners, ever paid/been paid for sex, sexually coerced, and substance use. In conclusion, MSM were involved in greater risk behaviors than those who only had female sex partners. Most MSM were living in Tel-Aviv and their estimated HIV prevalence was 1.0%. PMID- 26883584 TI - Neuroprotection by combination of resveratrol and enriched environment against ischemic brain injury in rats. AB - OBJECTIVES: Both resveratrol (RV) and enriched environment (EE) exert beneficial effects on neurological functional recovery after an ischemic brain injury. METHODS: The neuroprotective effect of combined treatment of RV and EE was examined in a rat model of middle cerebral artery occlusion (MCAO), aiming to further promote neurological functional recovery. RESULTS: The combined therapy of RV and EE clearly improved locomotor activity and behaviour examination, compared to the monotherapy of RV or EE alone. Stroke severity was also markedly ameliorated by the co-treatment. Mechanistic study revealed that the combined treatment reduced oxidative stress. Moreover, the detrimental ERK1/2 signalling upregulated by MCAO injury was markedly suppressed by the co-treatment, compared to RV or EE monotherapy. DISCUSSION: Altogether, the combined therapy of RV and EE showed a clearly enhanced neuroprotective effect, compared to RV or EE monotherapy, which might be a new strategy for the treatment of ischemic brain injury. PMID- 26883582 TI - Supervisors' perceptions of organizational policies are associated with their likelihood to accommodate back-injured workers. AB - Background Low back pain (LBP) is a major concern among North American workplaces and little is known regarding a supervisor's decision to support job accommodation for workers with LBP. The extent to which supervisors are included in a company's effort to institute disability management policies and practices and workplace safety climate are two factors that may influence a supervisor's decision to accommodate workers with LBP. Objective Determine the association between supervisors' perceptions of disability management policies, corporate safety culture and their likelihood of supporting job accommodations for workers with LBP. Methods We conducted a cross-sectional study of supervisors (N=796) recruited from a non-random, convenience sample of 19 Canadian and US employers. The outcome was supervisors' likeliness to support job accommodation and the exposure was global work safety culture and disability management policies and practices. A multivariable generalized linear modelling strategy was used and final models for each exposure were obtained after assessing potential effect modifiers and confounders. Results In the study, 796 eligible supervisors from 19 employers participated. Disability management policies and practices were positively associated with supervisors' likeliness to accommodate (beta=0.19; 95% CI: 0.13; 0.24) while no significant association was found between corporate safety culture (beta= -0.084; 95% CI: -0.19; 0.027) and supervisors' likeliness to accommodate. Conclusions Employers should ensure that proactive disability management policies and practices are clearly communicated to supervisors in order to improve job modification and return to work efforts. Implications for Rehabilitation Low back pain (LBP) is a major workplace concern and little is known regarding what factors are associated with a supervisor's likelihood to support job accommodation for workers with LBP. The objective of this article was to determine the association between supervisors' perceptions of disability management policies and practices, corporate safety culture and their likelihood of support job accommodations for workers with LBP. Results suggest that disability management policies and practices are positively associated with supervisors' likelihood to accommodate while corporate safety culture is not. These results are important for employers as it suggests that employers should ensure that their disability management policies and practices are clearly communicated to supervisors in order to improve job accommodation and return to work efforts. PMID- 26883583 TI - Digital PCR for quantification of recurrent and potentially actionable somatic mutations in circulating free DNA from patients with diffuse large B-cell lymphoma. AB - Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies. We demonstrated that our dPCR assays were sufficiently sensitive to detect rare XPO1, EZH2, and MYD88 mutations in plasma cfDNA, with a sensitivity of 0.05%. cfDNA somatic mutation detection by dPCR seems to be a promising technique in the management of DLBCL, in addition to NGS experiments. PMID- 26883585 TI - Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria. AB - Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), expressed on P. falciparum-infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical P. falciparum samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation per se and disease severity within these data. This contrasts with the simple hypothesis that P. falciparum isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria. PMID- 26883587 TI - Towards Rational Design of a Toxoid Vaccine against the Heat-Stable Toxin of Escherichia coli. AB - Enterotoxigenic Escherichia coli(ETEC) is an important cause of diarrheal disease and death in children <5 years old. ETEC strains that express the heat-stable toxin (ST), with or without the heat-labile toxin, are among the four most important diarrhea-causing pathogens. This makes ST an attractive target for an ETEC vaccine. An ST vaccine should be nontoxic and elicit an immune response that neutralizes native ST without cross-reacting with the human endogenous guanylate cyclase C receptor ligands. To identify variants of ST with no or low toxicity, we screened a library of all 361 possible single-amino-acid mutant forms of ST by using the T84 cell assay. Moreover, we identified mutant variants with intact epitopes by screening for the ability to bind neutralizing anti-ST antibodies. ST mutant forms with no or low toxicity and intact epitopes are termed toxoid candidates, and the top 30 candidates all had mutations of residues A14, N12, and L9. The identification of nontoxic variants of L9 strongly suggests that it is a novel receptor-interacting residue, in addition to the previously identified N12, P13, and A14 residues. The screens also allowed us to map the epitopes of three neutralizing monoclonal antibodies, one of which cross-reacts with the human ligand uroguanylin. The common dominant epitope residue for all non-cross reacting antibodies was Y19. Our results suggest that it should be possible to rationally design ST toxoids that elicit neutralizing immune responses against ST with minimal risk of immunological cross-reactivity. PMID- 26883586 TI - Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi. AB - Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n = 8 each) and a schistosomiasis control group (n = 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n = 8) were intravenously inoculated with 10(5) Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P = 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P = 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. PMID- 26883588 TI - A Plasmodium yoelii Mei2-Like RNA Binding Protein Is Essential for Completion of Liver Stage Schizogony. AB - Plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. RNA binding proteins (RBPs) provide one mechanism for modulation of RNA function. To explore the role of Plasmodium RBPs during parasite replication, we searched for RBPs that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. We identified a parasite ortholog of the Mei2 (Meiosis inhibited 2) RBP that is conserved among Plasmodium species (PlasMei2) and exclusively transcribed in liver stage parasites. Epitope-tagged Plasmodium yoelii PlasMei2 was expressed only during liver stage schizogony and showed an apparent granular cytoplasmic location. Knockout of PlasMei2 (plasmei2(-)) in P. yoelii only affected late liver stage development. The P. yoelii plasmei2(-) liver stage size increased progressively until late in development, similar to wild-type parasite development. However, P. yoelii plasmei2(-) liver stage schizonts exhibited an abnormal DNA segregation phenotype and failed to form exoerythrocytic merozoites. Consequently the cellular integrity of P. yoelii plasmei2(-) liver stages became increasingly compromised late in development and the majority of P. yoelii plasmei2(-) underwent cell death by the time wild-type liver stages mature and release merozoites. This resulted in a complete block of P. yoelii plasmei2(-) transition from liver stage to blood stage infection in mice. Our results show for the first time the importance of a Plasmodium RBP in the coordinated progression of late liver stage schizogony and maturation of new invasive forms. PMID- 26883589 TI - The Campylobacter jejuni Ferric Uptake Regulator Promotes Acid Survival and Cross Protection against Oxidative Stress. AB - Campylobacter jejuni is a prevalent cause of bacterial gastroenteritis in humans worldwide. The mechanisms by which C. jejuni survives stomach acidity remain undefined. In the present study, we demonstrated that the C. jejuni ferric uptake regulator (Fur) plays an important role in C. jejuni acid survival and acid induced cross-protection against oxidative stress. A C. jejuni Deltafur mutant was more sensitive to acid than the wild-type strain. Profiling of the acid stimulon of the C. jejuni Deltafur mutant allowed us to uncover Fur-regulated genes under acidic conditions. In particular, Fur was found to upregulate genes involved in flagellar and cell envelope biogenesis upon acid stress, and mutants with deletions of these genes were found to be defective in surviving acid stress. Interestingly, prior acid exposure of C. jejuni cross-protected against oxidative stress in a catalase (KatA)- and Fur-dependent manner. Western blotting and reverse transcription-quantitative PCR revealed increased expression of KatA upon acid stress. Electrophoretic mobility shift assays (EMSAs) demonstrated that the binding affinity between Fur and the katA promoter is reduced in vitro under conditions of low pH, rationalizing the higher levels of expression of katA under acidic conditions. Strikingly, the Deltafur mutant exhibited reduced virulence in both human epithelial cells and the Galleria mellonella infection model. Altogether, this is the first study showing that, in addition to its role in iron metabolism, Fur is an important regulator of C. jejuni acid responses and this function cross-protects against oxidative stress. Moreover, our results clearly demonstrate Fur's important role in C. jejuni pathogenesis. PMID- 26883590 TI - The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis. AB - The Yersinia high-pathogenicity island (HPI) is common to multiple virulence strategies used by Escherichia coli strains associated with urinary tract infection (UTI). Among the genes in this island are ybtP and ybtQ, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III) yersiniabactin import in Yersinia pestis In this study, we compared the impact of ybtPQ on a model E. coli cystitis strain during in vitro culture and experimental murine infections. A ybtPQ-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented in vitro during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 10(6) fold competitive infection defect in the subgroup of mice that progressed to high titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of Yersinia HPI-positive E. coli in uncomplicated clinical UTIs. PMID- 26883591 TI - Effects of B Cell Depletion on Early Mycobacterium tuberculosis Infection in Cynomolgus Macaques. AB - Although recent studies in mice have shown that components of B cell and humoral immunity can modulate the immune responses against Mycobacterium tuberculosis, the roles of these components in human and nonhuman primate infections are unknown. The cynomolgus macaque (Macaca fascicularis) model of M. tuberculosis infection closely mirrors the infection outcomes and pathology in human tuberculosis (TB). The present study used rituximab, an anti-CD20 antibody, to deplete B cells in M. tuberculosis-infected macaques to examine the contribution of B cells and humoral immunity to the control of TB in nonhuman primates during the acute phase of infection. While there was no difference in the overall pathology, disease profession, and clinical outcome between the rituximab-treated and untreated macaques in acute infection, analyzing individual granulomas revealed that B cell depletion resulted in altered local T cell and cytokine responses, increased bacterial burden, and lower levels of inflammation. There were elevated frequencies of T cells producing interleukin-2 (IL-2), IL-10, and IL-17 and decreased IL-6 and IL-10 levels within granulomas from B cell-depleted animals. The effects of B cell depletion varied among granulomas in an individual animal, as well as among animals, underscoring the previously reported heterogeneity of local immunologic characteristics of tuberculous granulomas in nonhuman primates. Taken together, our data clearly showed that B cells can modulate the local granulomatous response in M. tuberculosis-infected macaques during acute infection. The impact of these alterations on disease progression and outcome in the chronic phase remains to be determined. PMID- 26883592 TI - Experimental Models of Vaginal Candidiasis and Their Relevance to Human Candidiasis. AB - Vulvovaginal candidiasis (VVC) is a high-incidence disease seriously affecting the quality of life of women worldwide, particularly in its chronic, recurrent forms (RVVC), and with no definitive cure or preventive measure. Experimental studies in currently used rat and mouse models of vaginal candidiasis have generated a large mass of data on pathogenicity determinants and inflammation and immune responses of potential importance for the control of human pathology. However, reflection is necessary about the relevance of these rodent models to RVVC. Here we examine the chemical, biochemical, and biological factors that determine or contrast the forms of the disease in rodent models and in women and highlight the differences between them. We also appeal for approaches to improve or replace the current models in order to enhance their relevance to human infection. PMID- 26883593 TI - Mutagenesis and Functional Analysis of the Bacterial Arginine Glycosyltransferase Effector NleB1 from Enteropathogenic Escherichia coli. AB - Enteropathogenic Escherichia coli (EPEC) interferes with host cell signaling by injecting virulence effector proteins into enterocytes via a type III secretion system (T3SS). NleB1 is a novel T3SS glycosyltransferase effector from EPEC that transfers a single N-acetylglucosamine (GlcNAc) moiety in an N-glycosidic linkage to Arg(117) of the Fas-associated death domain protein (FADD). GlcNAcylation of FADD prevents the assembly of the canonical death-inducing signaling complex and inhibits Fas ligand (FasL)-induced cell death. Apart from the DXD catalytic motif of NleB1, little is known about other functional sites in the enzyme. In the present study, members of a library of 22 random transposon-based, in-frame, linker insertion mutants of NleB1 were tested for their ability to block caspase 8 activation in response to FasL during EPEC infection. Immunoblot analysis of caspase-8 cleavage showed that 17 mutant derivatives of NleB1, including the catalytic DXD mutant, did not inhibit caspase-8 activation. Regions of interest around the insertion sites with multiple or single amino acid substitutions were examined further. Coimmunoprecipitation studies of 34 site-directed mutants showed that the NleB1 derivatives with the E253A, Y219A, and PILN(63-66)AAAA (in which the PILN motif from residues 63 to 66 was changed to AAAA) mutations bound to but did not GlcNAcylate FADD. A further mutant derivative, the PDG(236-238)AAA mutant, did not bind to or GlcNAcylate FADD. Infection of mice with the EPEC-like mouse pathogen Citrobacter rodentium expressing NleBE253A and NleBY219A showed that these strains were attenuated, indicating the importance of residues E253 and Y219 in NleB1 virulence in vivo In summary, we identified new amino acid residues critical for NleB1 activity and confirmed that these are required for the virulence function of NleB1. PMID- 26883594 TI - Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes. AB - Small rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% of Ixodes ricinus-infested animals simultaneously harbored a nematode of the genus Heligmosomoides We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogen Borrelia afzelii Hosts experimentally coinfected with Heligmosomoides polygyrus and larval/nymphal I. ricinus ticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borne B. afzelii An observed trend for decreased local and systemic Th1 reactivity against B. afzelii in coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease. PMID- 26883598 TI - Can the mechanical activation (polishing) of screen-printed electrodes enhance their electroanalytical response? AB - The mechanical activation (polishing) of screen-printed electrodes (SPEs) is explored and shown to exhibit an improved voltammetric response (in specific cases) when polished with either commonly available alumina slurry or diamond spray. Proof-of-concept is demonstrated for the electrochemical sensing of nitrite where an increase in the voltammetric current is found using both polishing protocols, exhibiting an improved limit of detection (3sigma) and a two fold increase in the electroanalytical sensitivity compared to the respective un polished counterpart. It is found that mechanical activation/polishing increases the C/O ratio which significantly affects inner-sphere electrochemical probes only (whereas outer-sphere systems remain unaffected). Mechanical activation/polishing has the potential to be a simple pre-treatment technique that can be extended and routinely applied towards other analytes for an observable improvement in the electroanalytical response. PMID- 26883595 TI - The RNA-Binding Chaperone Hfq Is an Important Global Regulator of Gene Expression in Pasteurella multocida and Plays a Crucial Role in Production of a Number of Virulence Factors, Including Hyaluronic Acid Capsule. AB - The Gram-negative bacterium Pasteurella multocida is the causative agent of a number of economically important animal diseases, including avian fowl cholera. Numerous P. multocida virulence factors have been identified, including capsule, lipopolysaccharide (LPS), and filamentous hemagglutinin, but little is known about how the expression of these virulence factors is regulated. Hfq is an RNA binding protein that facilitates riboregulation via interaction with small noncoding RNA (sRNA) molecules and their mRNA targets. Here, we show that a P. multocida hfq mutant produces significantly less hyaluronic acid capsule during all growth phases and displays reduced in vivo fitness. Transcriptional and proteomic analyses of the hfq mutant during mid-exponential-phase growth revealed altered transcript levels for 128 genes and altered protein levels for 78 proteins. Further proteomic analyses of the hfq mutant during the early exponential growth phase identified 106 proteins that were produced at altered levels. Both the transcript and protein levels for genes/proteins involved in capsule biosynthesis were reduced in the hfq mutant, as were the levels of the filamentous hemagglutinin protein PfhB2 and its secretion partner LspB2. In contrast, there were increased expression levels of three LPS biosynthesis genes, encoding proteins involved in phosphocholine and phosphoethanolamine addition to LPS, suggesting that these genes are negatively regulated by Hfq-dependent mechanisms. Taken together, these data provide the first evidence that Hfq plays a crucial role in regulating the global expression of P. multocida genes, including the regulation of key P. multocida virulence factors, capsule, LPS, and filamentous hemagglutinin. PMID- 26883599 TI - Insights into the properties of the two enantiomers of trans-delta-viniferin, a resveratrol derivative: antioxidant activity, biochemical and molecular modeling studies of its interactions with hemoglobin. AB - Resveratrol is widely known as an antioxidant and anti-inflammatory molecule. The present study first reports the effects of trans-delta-viniferin (TVN), a dimer of resveratrol, on human erythrocytes. The antioxidant activity of TVN was tested using in vitro model systems such as hydroxy radical scavenging, DPPH and lipid peroxidation. In addition we have examined the influence of the 15R,22R- and 15S,22S-enantiomers (abbreviated R,R-TVN, and S,S-TVN, respectively) on anion transport, ATP release, caspase 3 activation. Given that hemoglobin (Hb) redox reactions are the major source of RBC oxidative stress, we also explored the effects of TVN on hemoglobin function. TVN showed moderate antioxidant properties and good protective activity from hemoglobin oxidation. Potential binding sites of R,R-TVN and S,S-TVN with oxy- and deoxy-Hb were also investigated through an extensive in silico docking approach and molecular dynamics calculations. The whole molecular modeling studies indicate that binding of R,R-TVN and S,S-TVN to Hb lacks of specific ligand-target interactions. This is the first report on the biological activity of the individual enantiomers of a resveratrol-related dimer. PMID- 26883596 TI - Identification of Antigenic Glycans from Schistosoma mansoni by Using a Shotgun Egg Glycan Microarray. AB - Infection of mammals by the parasitic helminth Schistosoma mansoni induces antibodies to glycan antigens in worms and eggs, but the differential nature of the immune response among infected mammals is poorly understood. To better define these responses, we used a shotgun glycomics approach in which N-glycans from schistosome egg glycoproteins were prepared, derivatized, separated, and used to generate an egg shotgun glycan microarray. This array was interrogated with sera from infected mice, rhesus monkeys, and humans and with glycan-binding proteins and antibodies to gather information about the structures of antigenic glycans, which also were analyzed by mass spectrometry. A major glycan antigen targeted by IgG from different infected species is the FLDNF epitope [Fucalpha3GalNAcbeta4(Fucalpha3)GlcNAc-R], which is also recognized by the IgG monoclonal antibody F2D2. The FLDNF antigen is expressed by all life stages of the parasite in mammalian hosts, and F2D2 can kill schistosomula in vitro in a complement-dependent manner. Different antisera also recognized other glycan determinants, including core beta-xylose and highly fucosylated glycans. Thus, the natural shotgun glycan microarray of schistosome eggs is useful in identifying antigenic glycans and in developing new anti-glycan reagents that may have diagnostic applications and contribute to developing new vaccines against schistosomiasis. PMID- 26883602 TI - Luminescent nanoparticle trapping with far-field optical fiber-tip tweezers. AB - We report stable and reproducible trapping of luminescent dielectric YAG:Ce(3+) nanoparticles with sizes down to 60 nm using far-field dual fiber tip optical tweezers. The particles are synthesized by a specific glycothermal route followed by an original protected annealing step, resulting in significantly enhanced photostability. The tweezers properties are analyzed by studying the trapped particles residual Brownian motion using video or reflected signal records. The trapping potential is harmonic in the transverse direction to the fiber axis, but reveals interference fringes in the axial direction. Large trapping stiffness of 35 and 2 pN MUm(-1) W(-1) is measured for a fiber tip-to-tip distance of 3 MUm and 300 nm and 60 nm particles, respectively. The forces acting on the nanoparticles are discussed within the dipolar approximation (gradient and scattering force contributions) or exact calculations using the Maxwell Stress Tensor formalism. Prospects for trapping even smaller particles are discussed. PMID- 26883601 TI - Bicoid gradient formation and function in the Drosophila pre-syncytial blastoderm. AB - Bicoid (Bcd) protein distributes in a concentration gradient that organizes the anterior/posterior axis of the Drosophila embryo. It has been understood that bcd RNA is sequestered at the anterior pole during oogenesis, is not translated until fertilization, and produces a protein gradient that functions in the syncytial blastoderm after 9-10 nuclear divisions. However, technical issues limited the sensitivity of analysis of pre-syncytial blastoderm embryos and precluded studies of oocytes after stage 13. We developed methods to analyze stage 14 oocytes and pre-syncytial blastoderm embryos, and found that stage 14 oocytes make Bcd protein, that bcd RNA and Bcd protein distribute in matching concentration gradients in the interior of nuclear cycle 2-6 embryos, and that Bcd regulation of target gene expression is apparent at nuclear cycle 7, two cycles prior to syncytial blastoderm. We discuss the implications for the generation and function of the Bcd gradient. PMID- 26883603 TI - Listening to Parents: A Qualitative Look at the Dental and Oral Care Experiences of Children with Autism Spectrum Disorder. AB - PURPOSE: Children with autism spectrum disorder (ASD) experience various barriers to optimal dental and oral care. The purpose of this study was to conduct focus groups of parents of children with autism spectrum disorder and subsequent qualitative analysis of the interviews in order to better understand problems in dental and oral care encountered by children with ASD. METHODS: Four focus groups, comprised of parents of children with ASD, ranging in age from three to 17 years old, were assembled. We took a semi-structured approach, facilitating discussion about home oral hygiene and professional dental care. Audiotapes were transcribed and independently coded by four investigators who then jointly identified themes. RESULTS: There were three overarching, interrelated themes: (1) There is variability between children with ASD in how they tolerate dental and oral care and in what facilitates such care. (2) Parents want more extensive dental care for their children with ASD. (3) Each child's dental and oral care should be individualized based on parents' input about the unique characteristics and needs of their child. CONCLUSIONS: There is no "one size fits all" approach to dental and oral care for children with autism spectrum disorder. Parents are valuable partners in informing the unique dental and oral care needs of their child with ASD. PMID- 26883604 TI - Characteristics of Mesiodens and Its Related Complications. AB - PURPOSE: The purpose of this study was to evaluate the effect of mesiodens on adjacent permanent anterior teeth according to mesiodens characteristics. METHODS: To evaluate complications associated with mesiodens, according to its characteristics, a total of 107 children were studied who had a chief complaint of mesiodens. The number, morphology, direction of eruption, position of mesiodens, root developmental stage and complications related to adjacent permanent maxillary central incisors (APMCIs) were evaluated by radiographic imaging. RESULTS: The final sample was 107 children and total number of mesiodens was 153. Among these patients, 67 percent showed clinical complications. The primary morphologic type was conical (96.1 percent) and the most common direction of eruption was inverted (56.2 percent). Most mesiodens (80.4 percent) were located on the palatal side of the APMCIs. CONCLUSIONS: The direction of mesiodens and the eruption period of adjacent permanent incisors affected the complication rate. The positional relationship between mesiodens and adjacent permanent central incisors had the strongest influence on both eruption disturbance and displacement of permanent central incisors. PMID- 26883605 TI - Existing Paradigms and Current Challenges in Adolescent Oral Health Research: A Call for Health Promotion Research Focusing on Low-income Adolescents. PMID- 26883606 TI - State-based Distribution of U.S. Pediatric Dentists in Private Practice. AB - PURPOSE: To determine state-based and regional ratios of U.S. pediatric dentists to children in 2010 and determine changes since 2000. METHODS: State-based enumeration of pediatric dentists in private practice (PDP) was determined from the American Academy of Pediatric Dentistry's 2010 Membership Directory. Number of children in each state was obtained from U.S. Census 2010 data. PDP ratio for each state was computed per 100,000 children. Changes in state-based PDP number and ratio to children were compared with 2000 data. RESULTS: There were 4,453 pediatric dentists in private practice across the United States, with a ratio of 6.00 per 100,000 children. California (583), Texas (378), New York (310), and Florida (231) had the largest PDP numbers. The Southern region (1,609) had the largest PDP number, while the Midwest (706) had the lowest number. PDP ratio to children was highest in the Northeast (7.61) and lowest in the Midwest (4.38). With the exceptions of Alaska, Vermont, and Wyoming, the PDP number and its ratio to children increased in all states between 2000 and 2010. CONCLUSIONS: Despite a generalized increase in practitioner number since 2000, noticeable differences persisted in 2010 among states in their pediatric dentist to children ratios. PMID- 26883607 TI - Variables Affecting General Anesthesia Time for Pediatric Dental Cases. AB - PURPOSE: The purpose of this study was to identify variables affecting procedural times for dental treatments performed in the operating room (OR) under general anesthesia. METHODS: A total of 2,264 OR cases at Boston Children's Hospital were included in the study. A series of patient, provider, and operational variables were studied, including: patient age, gender, American Society of Anesthesiologists (ASA) class, need for intraoperative radiographs, intubation type, provider type, referring provider type, referral date, waiting time between referral and OR, and symmetry of caries pattern. Analysis of variance, z test, t test, Pearson correlations, and regression modeling were used. RESULTS: Provider inexperience, need for obtaining radiographs, older age, higher ASA class, and oral intubation significantly increased surgical case times. Using the current OR case estimation resulted in an overestimation of 14.6 hours per month. Application of our regression model improved the accuracy of case time estimation by 7.9 hours per month. CONCLUSIONS: Overestimation of pediatric dental operating room cases exists, and identification of variables associated with these inaccuracies can aid providers in recapturing underutilized operating room times. PMID- 26883608 TI - Epidemiologic Study of Molar-incisor Hypomineralization in Schoolchildren in North-eastern Brazil. AB - PURPOSE: To determine the prevalence of molar-incisor hypomineralization (MIH) in children and possible factors associated with this disorder. METHODS: This was a cross-sectional observational study of 594 11- to 14-year-olds from Teresina, Piaui, Brazil. The diagnosis of MIH was made based on criteria set by the European Academy of Pediatric Dentistry. To investigate possible associated factors, mothers completed a questionnaire. A descriptive analysis of the data, chi-square, Mann-Whitney, and Fisher tests and Poisson regression (PR) were performed. RESULTS: The prevalence of MIH was 18.4 percent (95 percent confidence interval [CI] equals 15.20 to 21.50). The maxillary molars were the teeth most affected by MIH (36.1 percent). MIH patients showed a higher number of mean DMF-T (PR equals 2.18; 95 percent CI equals 1.46 to 2.85) than those not affected by the condition. There was an association between MIH and preterm birth (PR equals 1.76; 95 percent CI equals 1.22 to 2.12) and between MIH and respiratory distress at birth (PR equals 1.83; 95 percent CI equals 1.25 to 2.18). CONCLUSIONS: The prevalence of MIH in schoolchildren was 18.4 percent. Those with MIH had a greater mean DMF-T than those without MIH. Preterm birth and respiratory distress were associated with MIH. PMID- 26883609 TI - Comparison of Anesthetic Efficacy of Articaine and Lidocaine During Primary Maxillary Molar Extractions in Children. AB - PURPOSE: Recent evidence has shown that buccal infiltration with articaine alone can be used to anesthetize dental tissues for various dental procedures. The purpose of this study was to evaluate the efficacy of articaine compared to lidocaine for extraction of primary maxillary molars and assess whether palatal anesthesia could be achieved with buccal infiltration injection but without the need for palatal infiltration. METHODS: One hundred and two children requiring primary maxillary molar extraction were randomly selected to receive buccal infiltration using either articaine or lidocaine. During extraction, The Wong Baker Facial Pain Scale (FPS) was employed for subjective evaluation and Modified Behavior Pain Scale (MBPS) values, heart rate, and blood pressure were recorded for objective evaluation. Effectiveness of anesthesia was checked using subjective symptoms and probing. RESULTS: Palatal anesthesia with buccal infiltration could not be obtained in any of the groups. Statistically significantly higher MBPS pain scale values were seen with lidocaine as compared to articaine. FPS, heart rate, and blood pressure values presented no statistically significant difference in the two groups. CONCLUSIONS: Although buccal infiltration with articaine failed to provide adequate palatal anesthesia, it can still be considered a good alternative to lidocaine for local anesthesia in children. PMID- 26883610 TI - Pilot Study of the Canary System Use in the Diagnosis of Approximal Carious Lesions in Primary Molars. AB - PURPOSE: This study assessed the feasibility and ease of use of the Canary System in approximal carious lesion detection in primary molars. METHODS: Forty healthy five- to 12-year-olds, who presented to the Center for Pediatric Dentistry in Seattle, Wash., U.S.A., for initial or recall exams, were enrolled. Participants had one to two primary molars, with or without approximal radiographic radiolucencies. Four Canary System scans were performed at the approximal area of each study tooth. The maximum Canary number of the four scans was compared to bitewing radiographs. RESULTS: Seventy-five teeth were included in the final analysis. All study patients easily tolerated being scanned with the Canary System. The overall sensitivity and specificity of the Canary System, when compared to bitewing radiographs, was 81 percent and 35 percent, respectively. Among teeth without radiographic radiolucencies, the Canary System identified 65 percent (31 of 48) of study teeth as having carious lesions. CONCLUSIONS: The Canary System is a safe approximal caries detection device in five- to 12-year olds. When compared to bitewing radiographs, the specificity of the Canary System for approximal carious lesion detection in primary molars was low. However, this could indicate that the Canary System is detecting lesions earlier than radiographs. PMID- 26883611 TI - Retrospective Study of Retention of Stainless Steel Crowns and Pre-veneered Crowns on Primary Anterior Teeth. AB - PURPOSE: The purpose of this retrospective chart review was to explore the retention of anterior pre-veneered stainless steel crowns (NuSmile) and conventional stainless steel crowns (3M ESPE) placed on primary anterior teeth. METHODS: Records for children were reviewed over four years using the electronic record system axiUm. Data collected included child's age at time of crown placement, date of placement, tooth number, type of crown, patient behavior, treatment environment, provider type, crown presence, absence, and cementation success or failure at subsequent recall visits. RESULTS: A total of 637 anterior crowns in children treated with either or both crown types met this study's inclusion criteria. Of these crowns, 483 were NuSmile Signature crowns and 154 were stainless steel crowns. There was a nine percent failure rate for the NuSmile Signature crowns and a seven percent failure rate for the stainless steel crowns. There was no statistically significant difference in crown retention rates between the two groups (P<0.05). CONCLUSIONS: A full-coverage restoration that can follow the lifespan of the primary anterior dentition in high-risk children is needed. The results from this study indicate good crown retention rates for both crown types with no statistically significant difference between them (P<0.05). PMID- 26883612 TI - Sodium Hypochlorite Versus Formocresol and Ferric Sulfate Pulpotomies in Primary Molars: 18-month Follow-up. AB - PURPOSE: This study's purpose was to compare the clinical and radiographic success rates of 5.25 percent Sodium Hypochlorite (NaOCl) pulpotomies to Formocresol (FC) and Ferric Sulfate (FS) in decayed primary molars. METHODS: Eighty-one primary molars, randomly divided into three groups, were treated with one of three different pulpotomy materials; NaOCl, FC and FS. The outcomes of the different groups were assessed clinically and radiographically every six months over 18 months. Chi-square test was used to detect differences in outcome measures in all groups. RESULTS: At six months, clinical and radiographic success rates were 100 percent for each group (27/27). At 12 months, clinical success was 100 percent (24/24), 96 percent (24/25), and 95.7 percent (22/23) for NaOCl, FC, and FS respectively. The radiographic success was 95.8 percent (23/24) for NaOCl group, and 100 percent for FC (25/25), and FS (23/23). At 18 months, the clinical success was 83.3 percent (20/24), 96 percent (24/25), and 87 percent (20/23) for NaOCL, FC, and FS respectively. The 18 month radiographic success was 91.7 percent (22/24), 100 percent (25/25), and 95.7 percent (22/23) for NaOCl, FC, and FS respectively. No significant differences were found in clinical or radiographic outcomes between the three groups at six, 12 and 18 months. CONCLUSION: The three pulpotomy medicaments yielded similar outcomes. PMID- 26883613 TI - Prevalence of Antral Pseudocysts in the Pediatric Population. AB - PURPOSE: The purposes of this study were to determine the previously unreported prevalence of antral pseudocysts in an exclusively pediatric dental population, characterize their presentation, and investigate potential correlates to the presence of these lesions. METHODS: A tripartite chart review was conducted of 2,000 five- to 21-year-old pediatric dental patients at Yale-New Haven Hospital for the presence of antral pseudocysts identifiable on panoramic radiographs. Demographic, medical, and dental variables potentially influencing their pathogenesis were analyzed via descriptive statistics, odds ratios, and Fisher's exact test. RESULTS: Thirty-six antral pseudocysts were identified in the study sample (1.8 percent). They presented as asymptomatic solitary lesions with a slight male predominance and occurring with greater frequency in individuals with reported allergies. No significant relationship was found between maxillary extractions, orthodontics, obstructive sleep apnea, or history of orofacial trauma and the presence of antral pseudocysts. CONCLUSION: The prevalence of antral pseudocysts in the pediatric dental population falls among the lower end of ranges previously reported in the literature and may reflect their development over time in response to environmental exposures. PMID- 26883614 TI - Pediatric Oral Pathology: A Retrospective Survey of 4,554 Biopsies. AB - PURPOSE: The purposes of this study were to: (1) report patient age, gender, and anatomical information on a large number of pediatric oral biopsies in the United States; and (2) highlight differences in recent pediatric oral lesions compared to past pediatric studies and an adult population. METHODS: A total of 4,554 pediatric biopsies received over the past 13 years (2001-2015) were surveyed. Patient's age, gender, anatomical site of biopsy, and diagnosis were described under 10 diagnostic categories: (1) malignant neoplasm; (2) benign neoplasm; (3) infectious; (4) reactive; (5) precancerous; (6) developmental; (7) healthy tissue; (8) immune dysfunction; (9) physical trauma; and (10) other. RESULTS: A gradual increase in the number of biopsies with age was noted. The most common diagnosis observed was mucocele, consisting of 28 percent of all biopsies. Biopsies across pathological categories were most commonly obtained from the mandible. CONCLUSIONS: Biopsies received from a pediatric population are largely reactive in nature. Compared to an adult population, the pediatric population has a significantly lower rate of malignant and precancerous lesions but a higher rate of developmental diagnosis. A diverse array of pathoses was seen in the gingiva and mandible, whereas palatal mucosa and the floor of the mouth exhibited more variation. PMID- 26883615 TI - Management of Red Teeth in an International Patient with X-Linked Adrenoleukodystrophy. AB - Childhood cerebral X-linked adrenoleukodystrophy is a progressive, central nervous system, and endocrine disorder that typically leads to total neurologic disability and, eventually, death without appropriate, timely medical therapy. Hematopoietic stem cell transplantation has been found effective in slowing cerebral deterioration and improving long-term survival. The purpose of this case report was to describe the multidisciplinary management of red, discolored, pulpally treated primary molars identified in a nine-year-old Russian boy with childhood cerebral X-linked adrenoleukodystrophy preparing for myeloablative conditioning chemotherapy followed by hematopoietic stem cell transplantation. PMID- 26883617 TI - Erratum to: 'Home-based palliative approach for people with severe multiple sclerosis and their carers: study protocol for a randomized controlled trial'. PMID- 26883618 TI - Epidemiology and Antimicrobial Susceptibility of Gram-Negative Pathogens Causing Intra-abdominal Infections in Pediatric Patients in Europe-SMART 2011-2014. AB - Background: The most common type of intra-abdominal infection (IAI) is appendicitis, which occurs most frequently in children and young adults. Yet, few studies on the microbiology of pediatric IAI are available, which is problematic because antimicrobial therapy for IAI usually needs to be initiated before microbiological culture results are available. With this study, we aimed to assess whether resistance patterns in pediatric IAI in Europe that would help clinicians select empiric therapy can be identified. Methods: Gram-negative pathogens (n = 1259) were collected from pediatric patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 16 European countries from 2011 to 2014. Minimal inhibitory concentrations (MICs) and extended-spectrum beta-lactamase (ESBL) phenotype were determined by broth microdilution according to Clinical and Laboratory Standards Institute guidelines, and susceptibility was interpreted according to European Committee on Antimicrobial Susceptibility Testing guidelines. An IAI was defined as hospital- or community-associated if cultured >=48 or <48 hours after admission, respectively. Results: Overall, only imipenem and amikacin exceeded 90% susceptibility when all Gram-negative pathogens were combined, and ertapenem, cefepime, ceftazidime, piperacillin tazobactam, and levofloxacin reached at least 85%. However, resistance, ESBL positive, and multidrug-resistance (MDR) rates were substantially higher in isolates from patients with hospital-associated IAI than from those with community-associated IAI (eg, 14.1% vs 5.1% MDR isolates, respectively, among all Gram-negative pathogens), higher in isolates from intensive care units than in those from general wards, and higher in isolates from infants than in those from children >=1 year of age. In addition, MDR rates varied markedly within Europe. Conclusions: These results indicate that empiric therapy of pediatric IAI in Europe should reflect not only regional and local resistance patterns but also higher resistance rates in hospital-associated infections, intensive care units, and infants. PMID- 26883620 TI - Suppression subtractive hybridisation and real-time PCR for strain-specific quantification of the probiotic Bifidobacterium animalis BAN in broiler feed. AB - To ensure quality management during the production processes of probiotics and for efficacy testing in vivo, accurate tools are needed for the identification and quantification of probiotic strains. In this study, a strain-specific qPCR assay based on Suppression Subtractive Hybridisation (SSH) for identifying unique sequences, was developed to quantify the strain Bifidobacterium animalis BAN in broiler feed. Seventy potential BAN specific sequences were obtained after SSH of the BAN genome, with a pool of closely related strain genomes and subsequent differential screening by dot blot hybridisation. Primers were designed for 30 sequences which showed no match with any sequence database entry, using BLAST and FASTA. Primer specificity was assessed by qPCR using 45 non-target strains and species in a stepwise approach. Primer T39_S2 was the only primer pair without any unspecific binding properties and it showed a PCR efficiency of 80% with a Cq value of 17.32 for 20 ng BAN DNA. Optimised feed-matrix dependent calibration curve for the quantification of BAN was generated, ranging from 6.28 * 10(3)cfu g(-1) to 1.61 * 10(6)cfu g(-1). Limit of detection of the qPCR assay was 2 * 10(1)cfu g(-1) BAN. Applicability of the strain-specific qPCR assay was confirmed in a spiking experiment which added BAN to the feed in two concentrations, 2 * 10(6)cfu g(-1) and 2 * 10(4)cfu g(-1). Results showed BAN mean recovery rates in feed of 1.44 * 10(6) +/- 4.39 * 10(5)cfu g(-1) and 1.59 * 10(4) +/- 1.69 * 10(4)cfu g(-1), respectively. The presented BAN-specific qPCR assay can be applied in animal feeding trials, in order to control the correct inclusion rates of the probiotic to the feed, and it could further be adapted, to monitor the uptake of the probiotic into the gastrointestinal tract of broiler chickens. PMID- 26883621 TI - The first mile: community experience of outbreak control during an Ebola outbreak in Luwero District, Uganda. AB - BACKGROUND: A major challenge to outbreak control lies in early detection of viral haemorrhagic fevers (VHFs) in local community contexts during the critical initial stages of an epidemic, when risk of spreading is its highest ("the first mile"). In this paper we document how a major Ebola outbreak control effort in central Uganda in 2012 was experienced from the perspective of the community. We ask to what extent the community became a resource for early detection, and identify problems encountered with community health worker and social mobilization strategies. METHODS: Analysis is based on first-hand ethnographic data from the center of a small Ebola outbreak in Luwero Country, Uganda, in 2012. Three of this paper's authors were engaged in an 18 month period of fieldwork on community health resources when the outbreak occurred. In total, 13 respondents from the outbreak site were interviewed, along with 21 key informants and 61 focus group respondents from nearby Kaguugo Parish. All informants were chosen through non-probability sampling sampling. RESULTS: Our data illustrate the lack of credibility, from an emic perspective, of biomedical explanations which ignore local understandings. These explanations were undermined by an insensitivity to local culture, a mismatch between information circulated and the local interpretative framework, and the inability of the emergency response team to take the time needed to listen and empathize with community needs. Stigmatization of the local community--in particular its belief in amayembe spirits--fuelled historical distrust of the external health system and engendered community-level resistance to early detection. CONCLUSIONS: Given the available anthropological knowledge of a previous outbreak in Northern Uganda, it is surprising that so little serious effort was made this time round to take local sensibilities and culture into account. The "first mile" problem is not only a question of using local resources for early detection, but also of making use of the contextual cultural knowledge that has already been collected and is readily available. Despite remarkable technological innovations, outbreak control remains contingent upon human interaction and openness to cultural difference. PMID- 26883622 TI - Study protocol - efficacy of an attachment-based working alliance in the multimodal pain treatment. AB - BACKGROUND: The concept of attachment is relevant for the onset and development of chronic pain. Insecure attachment styles negatively affect therapeutic outcome. Insecurely attached patients seem to be less able to sustain positive effects of a multimodal treatment program. However, it has never been tested before if an attachment-oriented approach can improve treatment results of insecurely attached patients in a multimodal outpatient setting. To test this assumption, we compare the short- and long-term outcomes for pain patients who will receive multidisciplinary, attachment-oriented treatment with the outcomes for patients in a control group, who will receive the multidisciplinary state-of the-art treatment. METHODS: Two patient groups (baseline, attachment intervention) are assessed before treatment, after treatment, and at a 6 month follow-up. The study is conducted in a block design: After data collection of the first block (controls) and before as well as during data collection for the second block (treatment group), the health care personnel of the outpatient pain clinic receives training on attachment theory and its use in the therapeutic context. Pain intensity as measured with visual analogue scales and physical functioning will serve as the primary outcome measures. DISCUSSION: The design of our study allows for a continuous exchange of experienced team members, which may help bring about concrete attachment related guidelines for the enhancement of therapeutic outcome. This would be the first attempt at an attachment-oriented improvement of multimodal pain programs. CONCLUSION: An attachment-based approach may be a promising way to enhance long-term treatment outcomes for insecurely attached pain patients. TRIAL REGISTRATION: DRKS00008715 (registered on the 3(rd) of June 2015). PMID- 26883624 TI - Non-invasive ventilation and survival rates: the more, the better. A plea against its underuse. PMID- 26883623 TI - Time-dependent and independent neurophysiological indicators of prognosis in post anoxic coma subjects treated by therapeutic hypothermia. AB - BACKGROUND: Evaluation of prognostic value of electroencephalography (EEG) and somatosensory evoked potentials (SEP) according to different recording times. METHODS: A retrospective cohort study performed at the medical ICU of the AOU Careggi Teaching Hospital (Florence, Italy) of comatose adults (>18 years) after cardiac arrest (CA) and treated with therapeutic hypothermia (TH). We evaluated the Glasgow Coma Scale, EEG, and SEP performed at 12, 24, and 72 hrs after CA. Outcome was determined by the Glasgow Outcome Scale at 6 months after CA. RESULTS: We analyzed 167 patients. All patients with grade 1 EEG ("continuous") within 12 hours of CA recovered consciousness (false positive rate: 0.0%). Grade 2 EEG ("non-continuous") at 72 hours predicted a poor outcome with FPR=0.0%. Bilateral absent SEP at any time after CA predicted a poor outcome. CONCLUSIONS: EEG is a reliable time-dependent predictor of a good outcome (within 12 hours) and a poor outcome (after 72 hours). SEP is a time-independent predictor of a poor outcome. PMID- 26883625 TI - Pitfalls of brain monitoring using NIRS device. PMID- 26883627 TI - Does migratory distance affect fuelling in a medium-distance passerine migrant?: results from direct and step-wise simulated magnetic displacements. AB - In birds, fat accumulation before and during migration has been shown to be endogenously controlled and tuned by, among other factors, the Earth's magnetic field. However, our knowledge about the influence of the geomagnetic field on the fuelling in migrating birds is still limited to just a few nocturnally migrating passerine species. In order to study if variations of the magnetic field can also influence the fuelling of both day- and night-migrating passerines, we caught first-year dunnocks (Prunella modularis) and subjected them to three magnetic field conditions simulated by a system of magnetic coils: (1) local geomagnetic field of southern Sweden, (2) magnetic field corresponding to the centre of the expected wintering area, and (3) magnetic field met at the northern limit of the species' breeding distribution. We did not find a difference in mass increase between the birds kept in a local magnetic field and a field resembling their wintering area, irrespectively of the mode of magnetic displacement, i.e. direct or step-wise. However, the dunnocks magnetically displaced north showed a lower rate of fuelling in comparison to the control group, probably due to elevated activity. Compared with previous studies, our results suggest that the fuelling response to magnetic displacements during the migration period is specific to the eco-physiological situation. Future studies need to address if there is an effect of magnetic field manipulation on the level of migratory activity in dunnocks and how widespread the influence of local geomagnetic field parameters is on fuelling decisions in different bird species, which have different migratory strategies, distances and migration history. PMID- 26883626 TI - Prickle1 mutation causes planar cell polarity and directional cell migration defects associated with cardiac outflow tract anomalies and other structural birth defects. AB - Planar cell polarity (PCP) is controlled by a conserved pathway that regulates directional cell behavior. Here, we show that mutant mice harboring a newly described mutation termed Beetlejuice (Bj) in Prickle1 (Pk1), a PCP component, exhibit developmental phenotypes involving cell polarity defects, including skeletal, cochlear and congenital cardiac anomalies. Bj mutants die neonatally with cardiac outflow tract (OFT) malalignment. This is associated with OFT shortening due to loss of polarized cell orientation and failure of second heart field cell intercalation mediating OFT lengthening. OFT myocardialization was disrupted with cardiomyocytes failing to align with the direction of cell invasion into the outflow cushions. The expression of genes mediating Wnt signaling was altered. Also noted were shortened but widened bile ducts and disruption in canonical Wnt signaling. Using an in vitro wound closure assay, we showed Bj mutant fibroblasts cannot establish polarized cell morphology or engage in directional cell migration, and their actin cytoskeleton failed to align with the direction of wound closure. Unexpectedly, Pk1 mutants exhibited primary and motile cilia defects. Given Bj mutant phenotypes are reminiscent of ciliopathies, these findings suggest Pk1 may also regulate ciliogenesis. Together these findings show Pk1 plays an essential role in regulating cell polarity and directional cell migration during development. PMID- 26883628 TI - The intrinsic mechanics of B-DNA in solution characterized by NMR. AB - Experimental characterization of the structural couplings in free B-DNA in solution has been elusive, because of subtle effects that are challenging to tackle. Here, the exploitation of the NMR measurements collected on four dodecamers containing a substantial set of dinucleotide sequences provides new, consistent correlations revealing the DNA intrinsic mechanics. The difference between two successive residual dipolar couplings (DeltaRDCs) involving C6/8 H6/8, C3'-H3' and C4'-H4' vectors are correlated to the(31)P chemical shifts (deltaP), which reflect the populations of the BI and BII backbone states. The deltaPs are also correlated to the internucleotide distances (Dinter) involving H6/8, H2' and H2" protons. Calculations of NMR quantities on high resolution X ray structures and controlled models of DNA enable to interpret these couplings: the studied DeltaRDCs depend mostly on roll, while Dinterare mainly sensitive to twist or slide. Overall, these relations demonstrate how deltaP measurements inform on key inter base parameters, in addition to probe the BI<->BII backbone equilibrium, and shed new light into coordinated motions of phosphate groups and bases in free B-DNA in solution. Inspection of the 5' and 3' ends of the dodecamers also supplies new information on the fraying events, otherwise neglected. PMID- 26883629 TI - Rad18 confers hematopoietic progenitor cell DNA damage tolerance independently of the Fanconi Anemia pathway in vivo. AB - In cultured cancer cells the E3 ubiquitin ligase Rad18 activates Trans-Lesion Synthesis (TLS) and the Fanconi Anemia (FA) pathway. However, physiological roles of Rad18 in DNA damage tolerance and carcinogenesis are unknown and were investigated here. Primary hematopoietic stem and progenitor cells (HSPC) co expressed RAD18 and FANCD2 proteins, potentially consistent with a role for Rad18 in FA pathway function during hematopoiesis. However, hematopoietic defects typically associated with fanc-deficiency (decreased HSPC numbers, reduced engraftment potential of HSPC, and Mitomycin C (MMC) -sensitive hematopoiesis), were absent in Rad18(-/-) mice. Moreover, primary Rad18(-/-) mouse embryonic fibroblasts (MEF) retained robust Fancd2 mono-ubiquitination following MMC treatment. Therefore, Rad18 is dispensable for FA pathway activation in untransformed cells and the Rad18 and FA pathways are separable in hematopoietic cells. In contrast with responses to crosslinking agents, Rad18(-/-) HSPC were sensitive to in vivo treatment with the myelosuppressive agent 7,12 Dimethylbenz[a]anthracene (DMBA). Rad18-deficient fibroblasts aberrantly accumulated DNA damage markers after DMBA treatment. Moreover, in vivo DMBA treatment led to increased incidence of B cell malignancy in Rad18(-/-) mice. These results identify novel hematopoietic functions for Rad18 and provide the first demonstration that Rad18 confers DNA damage tolerance and tumor-suppression in a physiological setting. PMID- 26883630 TI - Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor. AB - Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions. PMID- 26883632 TI - The landscape of somatic mutations in protein coding genes in apparently benign human tissues carries signatures of relaxed purifying selection. AB - Mutations acquired during development and aging lead to inter- and intra-tissue genetic variations. Evidence linking such mutations to complex traits and diseases is rising. We detected somatic mutations in protein-coding regions in 140 benign tissue samples representing nine tissue-types (bladder, breast, liver, lung, prostate, stomach, thyroid, head and neck) and paired blood from 70 donors. A total of 80% of the samples had 2-39 mutations detectable at tissue-level resolution. Factors such as age and smoking were associated with increased burden of detectable mutations, and tissues carried signatures of distinct mutagenic processes such as oxidative DNA damage and transcription-coupled repair. Using mutational signatures, we predicted that majority of the mutations in blood originated in hematopoietic stem and early progenitor cells. Missense to silent mutations ratio and the persistence of potentially damaging mutations in expressed genes carried signatures of relaxed purifying selection. Our findings have relevance for etiology, diagnosis and treatment of diseases including cancer. PMID- 26883631 TI - Polymerases epsilon and ? repair dysfunctional telomeres facilitated by salt. AB - Damaged DNA can be repaired by removal and re-synthesis of up to 30 nucleotides during base or nucleotide excision repair. An important question is what happens when many more nucleotides are removed, resulting in long single-stranded DNA (ssDNA) lesions. Such lesions appear on chromosomes during telomere damage, double strand break repair or after the UV damage of stationary phase cells. Here, we show that long single-stranded lesions, formed at dysfunctional telomeres in budding yeast, are re-synthesized when cells are removed from the telomere-damaging environment. This process requires Pol32, an accessory factor of Polymerase delta. However, re-synthesis takes place even when the telomere damaging conditions persist, in which case the accessory factors of both polymerases delta and epsilon are required, and surprisingly, salt. Salt added to the medium facilitates the DNA synthesis, independently of the osmotic stress responses. These results provide unexpected insights into the DNA metabolism and challenge the current view on cellular responses to telomere dysfunction. PMID- 26883633 TI - Mapping of internal monophosphate 5' ends of Bacillus subtilis messenger RNAs and ribosomal RNAs in wild-type and ribonuclease-mutant strains. AB - The recent findings that the narrow-specificity endoribonuclease RNase III and the 5' exonuclease RNase J1 are not essential in the Gram-positive model organism,Bacillus subtilis, facilitated a global analysis of internal 5' ends that are generated or acted upon by these enzymes. An RNA-Seq protocol known as PARE (Parallel Analysis of RNA Ends) was used to capture 5' monophosphorylated RNA ends in ribonuclease wild-type and mutant strains. Comparison of PARE peaks in strains with RNase III present or absent showed that, in addition to its well known role in ribosomal (rRNA) processing, many coding sequences and intergenic regions appeared to be direct targets of RNase III. These target sites were, in most cases, not associated with a known antisense RNA. The PARE analysis also revealed an accumulation of 3'-proximal peaks that correlated with the absence of RNase J1, confirming the importance of RNase J1 in degrading RNA fragments that contain the transcription terminator structure. A significant result from the PARE analysis was the discovery of an endonuclease cleavage just 2 nts downstream of the 16S rRNA 3' end. This latter observation begins to answer, at least for B. subtilis, a long-standing question on the exonucleolytic versus endonucleolytic nature of 16S rRNA maturation. PMID- 26883634 TI - RUNX super-enhancer control through the Notch pathway by Epstein-Barr virus transcription factors regulates B cell growth. AB - In B cells infected by the cancer-associated Epstein-Barr virus (EBV), RUNX3 and RUNX1 transcription is manipulated to control cell growth. The EBV-encoded EBNA2 transcription factor (TF) activates RUNX3 transcription leading to RUNX3-mediated repression of the RUNX1 promoter and the relief of RUNX1-directed growth repression. We show that EBNA2 activates RUNX3 through a specific element within a -97 kb super-enhancer in a manner dependent on the expression of the Notch DNA binding partner RBP-J. We also reveal that the EBV TFs EBNA3B and EBNA3C contribute to RUNX3 activation in EBV-infected cells by targeting the same element. Uncovering a counter-regulatory feed-forward step, we demonstrate EBNA2 activation of a RUNX1 super-enhancer (-139 to -250 kb) that results in low-level RUNX1 expression in cells refractory to RUNX1-mediated growth inhibition. EBNA2 activation of the RUNX1 super-enhancer is also dependent on RBP-J. Consistent with the context-dependent roles of EBNA3B and EBNA3C as activators or repressors, we find that these proteins negatively regulate the RUNX1 super enhancer, curbing EBNA2 activation. Taken together our results reveal cell-type specific exploitation of RUNX gene super-enhancers by multiple EBV TFs via the Notch pathway to fine tune RUNX3 and RUNX1 expression and manipulate B-cell growth. PMID- 26883635 TI - The structure and intermolecular forces of DNA condensates. AB - Spontaneous assembly of DNA molecules into compact structures is ubiquitous in biological systems. Experiment has shown that polycations can turn electrostatic self-repulsion of DNA into attraction, yet the physical mechanism of DNA condensation has remained elusive. Here, we report the results of atomistic molecular dynamics simulations that elucidated the microscopic structure of dense DNA assemblies and the physics of interactions that makes such assemblies possible. Reproducing the setup of the DNA condensation experiments, we measured the internal pressure of DNA arrays as a function of the DNA-DNA distance, showing a quantitative agreement between the results of our simulations and the experimental data. Analysis of the MD trajectories determined the DNA-DNA force in a DNA condensate to be pairwise, the DNA condensation to be driven by electrostatics of polycations and not hydration, and the concentration of bridging cations, not adsorbed cations, to determine the magnitude and the sign of the DNA-DNA force. Finally, our simulations quantitatively characterized the orientational correlations of DNA in DNA arrays as well as diffusive motion of DNA and cations. PMID- 26883637 TI - Generating and using evidence: reflections from the perspective of implementation. PMID- 26883638 TI - Knowledge synthesis approaches-spoilt for choice? PMID- 26883639 TI - Paper on suicidality and aggression during antidepressant treatment was flawed and the press release was misleading. PMID- 26883636 TI - G-quadruplexes and helicases. AB - Guanine-rich DNA strands can fold in vitro into non-canonical DNA structures called G-quadruplexes. These structures may be very stable under physiological conditions. Evidence suggests that G-quadruplex structures may act as 'knots' within genomic DNA, and it has been hypothesized that proteins may have evolved to remove these structures. The first indication of how G-quadruplex structures could be unfolded enzymatically came in the late 1990s with reports that some well-known duplex DNA helicases resolved these structures in vitro. Since then, the number of studies reporting G-quadruplex DNA unfolding by helicase enzymes has rapidly increased. The present review aims to present a general overview of the helicase/G-quadruplex field. PMID- 26883641 TI - Basal ganglia germinoma presenting as a growing intratumoral hematoma in a 12 year-old boy. PMID- 26883640 TI - Pretreatment neutrophil-to-lymphocyte ratio predicts the prognosis in patients with metastatic prostate cancer. AB - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response in critical care patients, has been suggested as an independent prognostic factor for several solid malignancies. We investigated the utility of pretreatment NLR as a prognosticator in patients who presented with metastatic prostate cancer. METHODS: We first investigated the correlation between NLR and prostate-specific antigen (PSA) levels in 1464 men who had both tests and were found to have prostate cancer on their biopsies at our institution from 1999 to 2015. We then assessed the relationship between pretreatment NLR and the prognosis in 48 patients who were diagnosed with prostate cancer metastasized to the lymph node and/or bone. RESULTS: The NLR value was significantly elevated in men with higher PSA than in those with lower PSA (p < 0.001). In patients with metastatic prostate cancer, NLR (cut-off point of 3.37 determined by the AUROC curve) was correlated with both cancer-specific (p = 0.018) and overall (p = 0.008) survivals. CONCLUSIONS: Pretreatment NLR may function as a new biomarker that precisely predicts the prognosis in patients with metastatic prostate cancer. PMID- 26883643 TI - Ecological-network models link diversity, structure and function in the plankton food-web. AB - A planktonic food-web model including sixty-three functional nodes (representing auto- mixo- and heterotrophs) was developed to integrate most trophic diversity present in the plankton. The model was implemented in two variants - which we named 'green' and 'blue' - characterized by opposite amounts of phytoplankton biomass and representing, respectively, bloom and non-bloom states of the system. Taxonomically disaggregated food-webs described herein allowed to shed light on how components of the plankton community changed their trophic behavior in the two different conditions, and modified the overall functioning of the plankton food web. The green and blue food-webs showed distinct organizations in terms of trophic roles of the nodes and carbon fluxes between them. Such re-organization stemmed from switches in selective grazing by both metazoan and protozoan consumers. Switches in food-web structure resulted in relatively small differences in the efficiency of material transfer towards higher trophic levels. For instance, from green to blue states, a seven-fold decrease in phytoplankton biomass translated into only a two-fold decrease in potential planktivorous fish biomass. By linking diversity, structure and function in the plankton food-web, we discuss the role of internal mechanisms, relying on species-specific functionalities, in driving the 'adaptive' responses of plankton communities to perturbations. PMID- 26883644 TI - Stress in Parents of Children with Autism Spectrum Disorder: An Exploration of Demands and Resources. AB - We applied the ABCX model of stress and coping to assess the association between child and family demands, school-based resources (i.e., parent-teacher alliance and COMPASS, a consultation intervention), and two measures of parent stress: perceptions of the demands of raising a child (Child domain) and reactions to those demands (Parent domain). Data were analyzed from seventy-nine parents of children ages 3-9 with ASD participating in two randomized controlled trials of COMPASS. Stronger parent-teacher alliance correlated with decreased Parent domain stress and participation in COMPASS correlated with decreased Child domain stress after controlling for baseline stress. The study indicates that school-based resources can help reduce parent stress. PMID- 26883646 TI - Brief Report: Early Lexical Comprehension in Young Children with ASD: Comparing Eye-Gaze Methodology and Parent Report. AB - Lexical comprehension is commonly measured by parent report, but it may be difficult for parents of children with ASD to accurately judge their child's comprehension. We compared parent report to an eye-gaze measure of lexical comprehension in which participants observed pairs of images on a screen, along with accompanying speech that named one of the two images. Twenty-two toddlers with ASD participated. Trials were included if the target word was reported as unknown. Children spent significantly more time looking at the target after it was named than before (d = 0.66). These results provide evidence that eye-gaze measures can reveal emerging lexical knowledge in young children with ASD that may otherwise be overlooked. PMID- 26883642 TI - Proof-of Concept that an Acute Trophic Factors Intervention After Spinal Cord Injury Provides an Adequate Niche for Neuroprotection, Recruitment of Nestin Expressing Progenitors and Regeneration. AB - Trophic factor treatment has been shown to improve the recovery of brain and spinal cord injury (SCI). In this study, we examined the effects of TSC1 (a combination of insulin-like growth factor 1 and transferrin) 4 and 8 h after SCI at the thoracic segment level (T12) in nestin-GFP transgenic mice. TSC1 treatment for 4 and 8 h increased the number of nestin-expressing cells around the lesion site and prevented Wallerian degeneration. Treatment with TSC1 for 4 h significantly increased heat shock protein (HSP)-32 and HSP-70 expression 1 and 2 mm from lesion site (both, caudal and rostral). Conversely, the number of HSP-32 positive cells decreased after an 8-h TSC1 treatment, although it was still higher than in both, non-treated SCI and intact spinal cord animals. Furthermore, TSC1 increased NG2 expressing cell numbers and preserved most axons intact, facilitating remyelination and repair. These results support our hypothesis that TSC1 is an effective treatment for cell and tissue neuroprotection after SCI. An early intervention is crucial to prevent secondary damage of the injured SC and, in particular, to prevent Wallerian degeneration. PMID- 26883645 TI - Do Adults with High Functioning Autism or Asperger Syndrome Differ in Empathy and Emotion Recognition? AB - The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (1) their self-reported ability to empathise with others and/or (2) their ability to read mental states in others' eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and 'Reading the Mind in the Eyes' Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions. PMID- 26883647 TI - Life Satisfaction Among Mothers of Individuals with Prader-Willi Syndrome. AB - Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their families, the present study analyzed factors related to maternal life satisfaction, both cross-sectionally and over time. Results show that both child factors (e.g., behavior problems, hyperphagia) and maternal factors (e.g., stress, coping style) were significantly related to maternal life satisfaction. However, none of the tested variables predicted change in life satisfaction over time. Research and practice implications are discussed. PMID- 26883648 TI - History and First Descriptions of Autism: Asperger Versus Kanner Revisited. AB - When reading Michael Fitzgerald's chapter entitled 'Autism: Asperger's Syndrome History and First Descriptions' in 'Asperger's Disorder' edited by Rausch, Johnson and Casanova, a while ago, one of us was struck by his contention that Kanner was guilty of plagiarism as well as non-attribution of Asperger's 1938 paper 'Das psychisch abnorme kind' (Fitzgerald in Asperger's disorder. Informa Healthcare, New York, 2008) published in a Vienna weekly. Steve Silberman has discovered evidence that Kanner rescued Asperger's chief diagnostician from the Nazis in 1944 so must have been aware of Asperger's work and conclusions. Fitzgerald was on the right track but it appears that Kanner may have plagiarised Asperger's ideas rather than his 1938 paper. PMID- 26883650 TI - CORR Insights((r)): Greater Tuberosity Fractures: Does Fracture Assessment and Treatment Recommendation Vary Based on Imaging Modality? PMID- 26883649 TI - Collinearity of homoeologous group 3 chromosomes in the genus Hordeum and Secale cereale as revealed by 3H-derived FISH analysis. AB - Crop wild relatives are considered as important genetic resources of allelic diversity for domesticated crop species. Their utilization in breeding programs, however, is often limited due to crossing barriers and genome incompatibilities. Wild relatives of barley possess attractive properties and hence allelic diversity for adapting barley better to changing environmental conditions. Therefore, gaining a better knowledge about genomic synteny between cultivated barley and wild relatives of the same genus is an important task. To visualize genomic collinearity in related species, 22 genomic single-copy and 14 complementary DNA (cDNA) chromosome 3H-specific probes were mapped to the chromosomes of Hordeum bulbosum, Hordeum marinum, Hordeum pubiflorum, Hordeum murinum, and Secale cereale by fluorescent in situ hybridization (FISH). Most probes showed reliable signals confirming homoeology between cultivated barley and related species. Differences in order and position of FISH markers demonstrated sequence movements or small-scale chromosomal rearrangements within genus Hordeum and confirmed interchromosomal rearrangements between barley and rye. Comparison between repeat-free genomic and cDNA probes showed that gene containing single-copy genomic DNA (gDNA) probes are performing more reliably for FISH-based analysis of synteny. PMID- 26883651 TI - Is Needle Biopsy Clinically Useful in Preoperative Grading of Central Chondrosarcoma of the Pelvis and Long Bones? AB - BACKGROUND: Central chondrosarcoma of bone is graded on a scale of 1 to 3 according to histological criteria. Clinically, these tumors can be divided into low-grade (Grade 1) and high-grade (Grade 2, Grade 3, and dedifferentiated) chondrosarcomas. Although en bloc resection has been the most widely used treatment, it has become generally accepted that in selected patients with low grade chondrosarcomas of long bones, curettage is safe and effective. This approach requires an accurate preoperative estimation of grade to avoid under- or overtreatment, but prior reports have indicated that both imaging and biopsy do not always give an accurate prediction of grade. QUESTIONS/PURPOSES: (1) What is the concordance of image-guided needle preoperative biopsy and postoperative grading in central (intramedullary) chondrosarcomas of long bones, and how does this compare with the concordance of image-guided needle preoperative biopsy and postoperative grading in central pelvic chondrosarcomas? (2) What is the concordance of preoperative image-guided needle biopsy and postoperative findings in differentiating low-grade from high-grade central chondrosarcomas of long bones, and how does this compare with the concordance in central pelvic chondrosarcomas? METHODS: Between 1997 and 2014, in our institution, we treated 126 patients for central chondrosarcomas located in long bones and the pelvis. Of these 126 cases, 41 were located in the pelvis and the remaining 85 cases were located in long bones. This study considers 39 (95%) and 40 (47%) of them, respectively. We included all cases in which histological information was complete regarding preoperative and postoperative tumor grading. We excluded all cases with incomplete data sets or nondiagnostic preoperative biopsies. To evaluate the needle biopsy accuracy, we compared the histological tumor grade, obtained from the preoperative biopsy, with the final histological grade obtained from the postoperative surgical specimen. The weighted and nonweighted kappa statistics were used to evaluate the agreement. RESULTS: Concordance between the preoperative biopsy and the final pathological analysis in terms of histological grade was much higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (83% [33 of 40] versus 36% [14 of 39]; odds ratio, 8, 48). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma for the determination of histological grade (0.63; 95% confidence interval [CI], 0.34-0.91 versus 0.12; -0.32 to 0.57; p < 0.001). When categorizing the lesions as low grade or high grade, concordance between the preoperative biopsy and the final pathological analysis was much higher in long bone chondrosarcoma than in pelvic chondrosarcoma (90% [36 of 40] versus 67% [26 of 39]; odds ratio, 4, 5). Likewise, the weighted kappa coefficients were higher in long-bone chondrosarcoma than in pelvic chondrosarcoma (0.73; 95% CI, 0.51 0.94 versus 0.26; 0.04-0.48; p < 0.001). CONCLUSIONS: Image-guided needle biopsy, when performed by a specialist radiologist and evaluated by an experienced bone pathologist, is a useful tool in determining the histological grade of long-bone chondrosarcomas allowing identification of true low-grade tumors. The histological grade should be correlated with imaging and the clinical presentation, but under these circumstances, experienced tumor surgeons may use this information in planning surgical treatment. The same appears not to be true for pelvic lesions, in which histological grade established by needle biopsy should be interpreted with caution. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 26883652 TI - Pain Control and Functional Milestones in Total Knee Arthroplasty: Liposomal Bupivacaine versus Femoral Nerve Block. AB - BACKGROUND: Although pain management after total knee arthroplasty (TKA) affects rehabilitation, length of stay, and functional outcomes, pain management for patients undergoing TKA has yet to be standardized. Femoral nerve blocks (FNBs) are commonly used as an adjunct; however, these can result in transient quadriceps weakness and have been associated with in-hospital falls. Periarticular infiltration of liposomal bupivacaine has been recently introduced as a long-acting analgesic that can be administered without affecting motor function. QUESTIONS/PURPOSES: (1) Does periarticular liposomal bupivacaine compared with FNB result in improved pain control as measured by pain scores and narcotic consumption? (2) How do liposomal bupivacaine and FNB compare in terms of gait and stairclimbing milestones and the proportion of patients who experienced a fall in the hospital? METHODS: Between September 2013 and October 2014, a retrospective analysis was conducted involving 24 surgeons who performed a total of 1373 unilateral, primary TKAs. From September 2013 to April 2014, the routine approach to TKA pain management pathway consisted of preoperative administration of oral analgesics, intraoperative anesthesia (preferred spinal or general), an ultrasound-guided FNB, intraoperative analgesic cocktail injection, patient-controlled analgesia, and oral and IV narcotics for pain as needed. A total of 583 patients were included in this study group. Starting May 2014, FNBs were discouraged and there was department-wide adoption of liposomal bupivacaine. Liposomal bupivacaine became routinely used in all patients undergoing TKA with no other changes made to the multimodal analgesia protocol at that time, and 527 patients in this study group were compared with the FNB cohort. Chart review on a total of 1110 patients was conducted by a research assistant who was not participating in patient care. During the inpatient stay, pain scores during 8 hour intervals, narcotic use, and physical therapy milestones were compared. RESULTS: With the numbers available, we detected no clinically important difference in pain scores throughout the hospital stay; however, patients treated with liposomal bupivacaine consumed very slightly less narcotics overall (96 +/- 62 versus 84 +/- 73 eq mg of morphine; [95% confidence interval, 11-13 mg]; p = 0.004) through postoperative Day 2 of inpatient hospitalization. Seventy-seven percent (406 of 527) of patients receiving liposomal bupivacaine achieved their gait milestones of clearing 100 feet of ambulation versus 60% (349 of 583) of patients receiving FNB (p < 0.001) before discharge. Likewise, 94% (497 of 527) of patients receiving liposomal bupivacaine completed stairs compared with 73% (427 of 583) of patients receiving FNB (p < 0.001). Patients who received liposomal bupivacaine were less likely to experience a fall during the hospital stay than were patients treated with FNB (3 of 527 [0.6%] versus 12 of 583 [2%]; p = 0.03). CONCLUSIONS: In the absence of strong data supporting FNB over liposomal bupivacaine, we have modified our TKA pain management protocols by adopting liposomal bupivacaine in lieu of FNBs, facilitating rapid rehabilitation while providing adequate pain control. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26883653 TI - Letter to the Editor: Does Combined Intra- and Extraarticular ACL Reconstruction Improve Function and Stability? A Meta-analysis. PMID- 26883654 TI - Do Patients After Chondrosarcoma Treatment Have Age-appropriate Bone Mineral Density in the Long Term? AB - BACKGROUND: In long-term survivors of osteosarcoma and Ewing sarcoma treated with the addition of radio- and chemotherapy, low bone mineral density (BMD) and fractures have been observed, presumably resulting from these adjuvants. Because patients with chondrosarcoma usually are not treated with conventional adjuvant treatment, observation of low BMD in patients with chondrosarcoma presumably would be the result of other mechanisms. However, BMD in patients with a history of chondrosarcoma has not been well characterized. QUESTIONS/PURPOSES: The aim of our study was to address the following questions: (1) Do long-term survivors of chondrosarcoma have normal BMD and, if not, which factors contribute to low BMD? (2) Is there a greater risk of fracture and does the Fracture Risk Assessment Tool (FRAX((r))) score reflect fracture likelihood? METHODS: All known patients with a history of chondrosarcoma treated at our institution before 2006 were identified. Of 127 patients believed to be alive at the time of this study, 30 agreed to participate in this study (11 females, 19 males; mean age at surgery, 39 +/- 12 years; mean followup, 12 +/- 5 years). With the data available, the 30 participants were not different from the 97 nonparticipants in terms of age, sex, BMI, tumor grade, tumor location (axial versus appendicular, lower extremity versus elsewhere), and use of any treatment known to influence osteopenia (chemotherapy, lower extremity surgery). BMD was measured and history of fractures was assessed using a questionnaire. The patients' BMD measurements in this study were sex- and age-matched with a normative sex- and age-categorized reference population reported by Kudlacek et al. Associations were tested by univariate regressions and ANOVAs of all measures of BMD and eligible oncologic and demographic factors. RESULTS: Eighteen of 30 (60%) patients had a pathologic BMD according to the WHO dual-energy x-ray absorptiometry definition, 15 (50%) had osteopenia, and three (10%) had osteoporosis. T-scores in the study cohort were lower than reference values for the femur neck (mean difference, 0.64; 95% CI, 0.27-1.01; p < 0.0015), but not for the spine (mean difference, 0.39; 95% CI, -0.06 to 0.84; p = 0.09). Thirteen patients (45%) reported a history of fractures not distinguishing between low and high impact. The incidence of fractures was 2.8 greater than expected from a comparison with a published microcensus survey of the Austrian population. No effect of the FRAX((r)) score on fracture risk could be identified (p = 0.057). CONCLUSIONS: Long-term survivors of chondrosarcoma appear to be at greater risk for having low BMD develop than the healthy population. Although these results are preliminary and based on a very small sampling of patients, if they can be confirmed in larger studies, BMD assessment by dual-energy x-ray absorptiometry might be considered as these patients are followed posttreatment by sarcoma care units. The reasons for low BMD still must be elucidated. LEVEL OF EVIDENCE: Level IV, prognostic study. PMID- 26883655 TI - Reply to the Letter to the Editor: Does Combined Intra- and Extraarticular ACL Reconstruction Improve Function and Stability? A Meta-analysis. PMID- 26883656 TI - Reconstruction After Hemipelvectomy With the Ice-Cream Cone Prosthesis: What Are the Short-term Clinical Results? AB - BACKGROUND: Reconstruction after internal hemipelvectomy resection likely provides better function than hindquarter amputation. However, many reconstruction methods have been used, complications with these approaches are common, and function often is poor; because of these issues, it seems important to investigate alternative implants and surgical techniques. QUESTIONS/PURPOSES: The purposes of this study were (1) to identify the frequency of surgical site complications and infection associated with the use of the Ice-Cream Cone prosthesis for reconstruction after hemipelvectomy for oncological indications; (2) to evaluate the Musculoskeletal Tumor Society (MSTS) outcomes scores in a small group of patients treated with this implant in the short term; and (3) to quantify the surgical margins and frequency of local recurrence in the short term in this group of patients. METHODS: Between 2008 and 2013, one center performed a total of 27 internal hemipelvectomies for oncological indications. Of those, 23 (85%) were treated with reconstruction. Our general indications for reconstruction were patients whose pelvic stability was affected by the resection and whose general condition was sufficiently strong to tolerate the reconstructive procedure. Of those patients undergoing reconstruction, 14 (61%) were treated with an Ice-Cream Cone-style implant (Coned(r); Stanmore Worldwide Ltd, Elstree, UK; and Socincer(r) custom-made implant for the pelvis, Gijon, Spain), whereas nine others were treated with other implants or allografts. The indications during this time for using the Ice-Cream Cone implant were pelvic tumors affecting the periacetabular area without iliac wing involvement. Of those 14, 10 were available for followup at a minimum of 2 years (median, 3 years; range, 2-5 years) unless a study endpoint (wound complication, infection, or local recurrence) was observed earlier. Study endpoints were ascertained by chart review performed by one of the authors. RESULTS: Surgical site complications occurred in five patients. Of those, two developed superficial infections with necrosis,two developed deep infections, and one patient developed wound necrosis without apparent infection. No prostheseswere removed as a result of these complications [corrected]. Median MSTS score was 19 out of 30 when 0 is the worst possible result and 30 a perfect function and emotional status. Five of seven primary tumors had wide margin surgery and three of seven developed local recurrences by the end of the followup. CONCLUSIONS: Pelvic reconstruction with the Ice-Cream Cone prosthesis yielded fair functional results at short-term followup. Longer term surveillance is called for to see whether this implant will represent an improvement over available reconstructive alternatives such as allograft, custom-made implants, and saddle prostheses. We are cautiously optimistic and continue to use this implant when we need to reconstruct the periacetabular area in patients without Enneking Zone 1 involvement. LEVEL OF EVIDENCE: Level IV, therapeutic study. PMID- 26883657 TI - CORR Insights((r)): Is there an Increase in Valgus Deviation in Tibial Distraction Using the Lengthening Over Nail Technique? PMID- 26883658 TI - CORR Insights((r)): Cathodic Voltage-controlled Electrical Stimulation Plus Prolonged Vancomycin Reduce Bacterial Burden of a Titanium Implant-associated Infection in a Rodent Model. PMID- 26883659 TI - The Ethical Imperative to Move to a Seven-Day Care Model. AB - Whilst the nature of human illness is not determined by time of day or day of week, we currently structure health service delivery around a five-day delivery model. At least one country is endeavouring to develop a systems-based approach to planning a transition from five- to seven-day healthcare delivery models, and some services are independently instituting program reorganization to achieve these ends as research, amongst other things, highlights increased mortality and morbidity for weekend and after-hours admissions to hospitals. In this article, we argue that this issue does not merely raise instrumental concerns but also opens up a normative ethical dimension, recognizing that clinical ethical dilemmas are impacted on and created by systems of care. Using health policy ethics, we critically examine whether our health services, as currently structured, are at odds with ethical obligations for patient care and broader collective goals associated with the provision of publicly funded health services. We conclude by arguing that a critical health policy ethics perspective applying relevant ethical values and principles needs to be included when considering whether and how to transition from five-day to seven-day models for health delivery. PMID- 26883660 TI - Photoacoustic monitoring of tumor and normal tissue response to radiation. AB - Hypoxia is a recognized characteristic of tumors that influences efficacy of radiotherapy (RT). Photoacoustic imaging (PAI) is a relatively new imaging technique that exploits the optical characteristics of hemoglobin to provide information on tissue oxygenation. In the present study, PAI based measures of tumor oxygen saturation (%sO2) were compared to oxygen-enhanced magnetic resonance imaging (MRI) measurements of longitudinal relaxation rate (R1 = 1/T1) and ex-vivo histology in patient derived xenograft (PDX) models of head and neck cancer. PAI was utilized to assess early changes (24 h) in %sO2 following RT and chemoRT (CRT) and to assess changes in salivary gland hemodynamics following radiation. A significant increase in tumor %sO2 and R1 was observed following oxygen inhalation. Good spatial correlation was observed between PAI, MRI and histology. An early increase in %sO2 after RT and CRT detected by PAI was associated with significant tumor growth inhibition. Twenty four hours after RT, PAI also detected loss of hemodynamic response to gustatory stimulation in murine salivary gland tissue suggestive of radiation-induced vascular damage. Our observations illustrate the utility of PAI in detecting tumor and normal tissue hemodynamic response to radiation in head and neck cancers. PMID- 26883661 TI - Efficacy and Safety of Aclidinium/Formoterol versus Tiotropium in COPD: Results of an Indirect Treatment Comparison. AB - INTRODUCTION: The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 MUg twice daily compared to tiotropium 18 MUg once daily in adult patients with moderate-to severe chronic obstructive pulmonary disease (COPD). METHODS: A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with >=1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control. RESULTS: Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization. CONCLUSION: Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile. FUNDING: AstraZeneca. PMID- 26883663 TI - Postural sensory correlates of freezing of gait in Parkinson's disease. AB - INTRODUCTION: To elucidate the unique patterns of postural sensory deficits contributing to freezing of gait (FOG) in patients with Parkinson's disease (PD) and to identify postural sensory modalities that correlate with FOG severity. METHODS: Twenty-five PD patients with FOG, 22 PD patients without FOG, and 26 age matched controls were evaluated using a sensory organization test and clinical measures including the Unified Parkinson's Disease Rating Scale motor score, Montreal Cognitive Assessment, Frontal Assessment Battery, Activities-specific Balance Confidence, Beck Anxiety Inventory, Beck Depression Inventory, and Berg Balance Scale. Multivariable logistic regression analysis was performed for posturographic parameters and possible confounders to determine postural sensory contributors to FOG. We also correlated FOG severity, measured using a New Freezing of Gait Questionnaire, with posturographic parameters. RESULTS: PD patients with FOG showed worse postural sensory processing compared with those without FOG. In particular, the inability to use the vestibular information (odds ratio [OR] 1.447; 95% confidential interval [CI]: 1.120, 1.869) and poor control over the perturbed somatosensory inputs (OR 2.904; 95% CI: 1.028, 8.202) significantly contributed to FOG. Among PD patients with FOG, FOG severity was correlated with higher reliance on visual information (rho = -0.432, p = 0.039). CONCLUSIONS: Postural sensory deficits involving specific sensory modalities are strongly associated with FOG. Quantitative measurement of postural sensory deficits in PD patients with FOG may provide a better understanding of pathomechanisms of FOG and increase the efficacy of sensory cueing strategies for alleviating FOG, by more accurately identifying suitable patients for rehabilitative therapies. PMID- 26883662 TI - Enhanced cellulase production by Trichoderma harzianum by cultivation on glycerol followed by induction on cellulosic substrates. AB - The use of glycerol obtained as an intermediate of the biodiesel manufacturing process as carbon source for microbial growth is a potential alternative strategy for the production of enzymes and other high-value bioproducts. This work evaluates the production of cellulase enzymes using glycerol for high cell density growth of Trichoderma harzianum followed by induction with a cellulosic material. Firstly, the influence of the carbon source used in the pre-culture step was investigated in terms of total protein secretion and fungal morphology. Enzymatic productivity was then determined for cultivation strategies using different types and concentrations of carbon source, as well as different feeding procedures (batch and fed-batch). The best strategy for cellulase production was then further studied on a larger scale using a stirred tank bioreactor. The proposed strategy for cellulase production, using glycerol to achieve high cell density growth followed by induction with pretreated sugarcane bagasse, achieved enzymatic activities up to 2.27 +/- 0.37 FPU/mL, 106.40 +/- 8.87 IU/mL, and 9.04 +/- 0.39 IU/mL of cellulase, xylanase, and beta-glucosidase, respectively. These values were 2 times higher when compared to the control experiments using glucose instead of glycerol. This novel strategy proved to be a promising approach for improving cellulolytic enzymes production, and could potentially contribute to adding value to biomass within the biofuels sector. PMID- 26883665 TI - Two distinctive energy migration pathways of monolayer molecules on metal nanoparticle surfaces. AB - Energy migrations at metal nanomaterial surfaces are fundamentally important to heterogeneous reactions. Here we report two distinctive energy migration pathways of monolayer adsorbate molecules on differently sized metal nanoparticle surfaces investigated with ultrafast vibrational spectroscopy. On a 5 nm platinum particle, within a few picoseconds the vibrational energy of a carbon monoxide adsorbate rapidly dissipates into the particle through electron/hole pair excitations, generating heat that quickly migrates on surface. In contrast, the lack of vibration-electron coupling on approximately 1 nm particles results in vibrational energy migration among adsorbates that occurs on a twenty times slower timescale. Further investigations reveal that the rapid carbon monoxide energy relaxation is also affected by the adsorption sites and the nature of the metal but to a lesser extent. These findings reflect the dependence of electron/vibration coupling on the metallic nature, size and surface site of nanoparticles and its significance in mediating energy relaxations and migrations on nanoparticle surfaces. PMID- 26883664 TI - Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure. AB - Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL/6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex specific. Sex specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation. PMID- 26883666 TI - Why the European Association of Nuclear Medicine has declined to endorse the 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. PMID- 26883667 TI - Metabolic and molecular relative percentage coreduction in patients with locally advanced rectal cancer treated with neoadjuvant therapy. AB - PURPOSE: Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR) and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumour progression and are important targets for cancer therapeutics. (18)F-FDG maximum standardized uptake value (SUVmax) on PET/CT is a marker of tumour metabolic activity. The purpose of this study was to measure percentage reductions in SUVmax (?SUVmax%), VEGFR-2 (?VEGFR-2%), EGFR (?EGFR%) and COX-2 (?COX-2%) in patients with locally advanced rectal cancer (LARC) after preoperative treatment, and to correlate the changes in these markers of response with pathological response in terms of tumour regression grade (TRG) using Rodel's scale and long-term clinical outcome. METHODS: VEGFR-2, EGFR and COX-2 were measured using a quantitative and qualitative compound immunohistochemistry analysis (immunoreactive score) of the pretreatment endoscopic biopsy and definitive surgical specimens. Composite indexes using ?SUVmax% and the three molecules were developed to differentiate patients with metabolic and molecular responses from nonresponders. Cox proportional hazards model was used to explore associations between the tumour markers, disease-free survival (DFS) and overall survival (OS). RESULTS: The analysis included 38 patients with a median follow-up of 86 months (range 5 - 113 months). The ?VEGFR-2%/?SUVmax% index correctly identified 13 of 19 pathological responders (TRG 3 and 4) and 17 of 19 nonresponders (TRG 0 - 2) (sensitivity 68 %, specificity 89 %, accuracy 79 %, positive predictive value 87 %, negative predictive value 74 %). In multivariate analysis, only the ?VEGFR-2%/?SUVmax% index was associated with DFS (HR 0.11, p = 0.001) and OS (HR 0.15, p = 0.02). CONCLUSION: In patients with LARC the ?VEGFR 2%/?SUVmax% response index is associated with outcome. Determination of the optimal diagnostic cut-off level for this novel biomarker association should be explored. Evaluation in a clinical trial is required to determine whether selected patients could benefit from treatment with a VEGFR-targeted therapeutic agent. PMID- 26883668 TI - Characterization of wheat-Secale africanum chromosome 5R(a) derivatives carrying Secale specific genes for grain hardness. AB - MAIN CONCLUSION: New wheat- Secale africanum chromosome 5R (a) substitution and translocation lines were developed and identified by fluorescence in situ hybridization and molecular markers, and chromosome 5R (a) specific genes responsible for grain hardness were isolated. The wild species, Secale africanum Stapf. (genome R(a)R(a)), serves as a valuable germplasm resource for increasing the diversity of cultivated rye (S. cereale L., genome RR) and providing novel genes for wheat improvement. In the current study, fluorescence in situ hybridization (FISH) and molecular markers were applied to characterize new wheat S. africanum chromosome 5R(a) derivatives. Labeled rye genomic DNA (GISH) and the Oligo-probes pSc119.2 and pTa535 (FISH) were used to study a wheat-S. africanum amphiploid and a disomic 5R(a) (5D) substitution, and to identify a T5DL.5R(a)S translocation line and 5R(a)S and 5R(a)L isotelosome lines. Twenty-one molecular markers were mapped to chromosome 5R(a) arms which will facilitate future rapid identification of 5R(a) introgressions in wheat backgrounds. Comparative analysis of the molecular markers mapped on 5R(a) with homoeologous regions in wheat confirmed a deletion on the chromosome T5DL.5R(a)S, which suggests that the wheat S. africanum Robertsonian translocation involving homologous group 5 may not be fully compensating. Complete coding sequences at the paralogous puroindoline-a (Pina) and grain softness protein gene (Gsp-1) loci from S. africanum were cloned and localized onto the short arm of chromosome 5R(a). The S. africanum chromosome 5R(a) substitution and translocation lines showed a reduction in the hardness index, which may be associated with the S. africanum- specific Pina and Gsp-1 gene sequences. The present study reports the production of novel wheat-S. africanum chromosome 5R(a) stripe rust resistant derivatives and new rye-specific molecular markers, which may find application in future use of wild Secale genome resources for grain quality studies and disease resistance breeding. PMID- 26883669 TI - Key Aspects of a Sustainable Health Insurance System in Germany. AB - BACKGROUND: The main goals of health-care systems are to improve the health of the population they serve, respond to people's legitimate expectations, and offer fair financing. As a result, the health system in Germany is subject to continuous adaption as well as public and political discussions about its design. OBJECTIVE: This paper analyzes the key challenges for the German health-care system and the underlying factors driving these challenges. We aim to identify possible solutions to put the German health-care system in a better position to face these challenges. METHODS: We utilize a broad array of methods to answer these questions, including a review of the published and grey literature on health-care planning in Germany, semi-structured interviews with stakeholders in the system, and an online questionnaire. RESULTS: We find that the most urgent (and manageable) aspects that merit attention are holistic hospital planning, initiatives to increase (administrative) innovation in the health-care system, incentives to increase prevention, and approaches to increase analytical quality assurance. CONCLUSION: We found that hospital planning, innovation, quality control, and prevention, are considered to be the topics most in need of attention in the German health system. PMID- 26883670 TI - Systemic T Cells and Monocyte Characteristics in Patients with Denture Stomatitis. AB - PURPOSE: Chronic inflammatory disorders of the oral cavity, such as periodontitis, were recently linked to systemic immune activation. Since fungal oral infections have not yet been studied in this respect, the aim of our study is to determine whether the local inflammation caused by oral fungal infection of the palatal tissue (denture stomatitis-DS) is associated with the systemic inflammatory response. This question is becoming essential as the population ages. MATERIALS AND METHODS: Peripheral blood of DS patients (n = 20) and control patients (n = 24) was assessed with flow cytometry to determine lymphocyte and monocyte profiles. Intracellular cytometric analysis was carried out to establish cytokine production by T cells. DS was diagnosed based on clinical symptoms of DS such as swelling and redness of oral mucosa, confirmed by microbiological swabs for fungal colonization with Candida species. The control group was recruited from denture users without clinical and microbiological signs of oral infections. RESULTS: Percentages of peripheral lymphocytes, T cells, monocytes, and their subpopulations were similar in both studied groups. The exception was median percentages of CD25+ T cell subsets, which were significantly lower in DS patients than in control subjects. This reduction was observed in both CD4 T cell subset (16.7% and 28.1%; p = 0.0006) and CD8 T cell subset (4.6% and 7.0%; p = 0.007) CONCLUSIONS: While DS and associated local fungal infection do not overtly affect activation of monocytes or lymphocytes, the number of CD 25+ T cells is significantly lower in the DS patients, possibly indicating limited potential for the infection clearance in denture-using aging patients. PMID- 26883672 TI - Precision Medicine: What Do We Expect in the Scope of Basic Biomedical Sciences? PMID- 26883673 TI - A risk stratification tool for exacerbations of COPD: time to switch to DECAF. PMID- 26883675 TI - The restrictive-obstructive continuum and the failing heart. PMID- 26883671 TI - Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. AB - Long non-coding RNAs (lncRNAs) play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides. PMID- 26883674 TI - Distinct severity stages of obstructive sleep apnoea are correlated with unique dyslipidaemia: large-scale observational study. AB - BACKGROUND: Dyslipidaemia is an intermediary exacerbation factor for various diseases but the impact of obstructive sleep apnoea (OSA) on dyslipidaemia remains unclear. METHODS: A total of 3582 subjects with suspected OSA consecutively admitted to our hospital sleep centre were screened and 2983 (2422 with OSA) were included in the Shanghai Sleep Health Study. OSA severity was quantified using the apnoea-hypopnea index (AHI), the oxygen desaturation index and the arousal index. Biochemical indicators and anthropometric data were also collected. The relationship between OSA severity and the risk of dyslipidaemia was evaluated via ordinal logistic regression, restricted cubic spline (RCS) analysis and multivariate linear regressions. RESULTS: The RCS mapped a nonlinear dose-effect relationship between the risk of dyslipidaemia and OSA severity, and yielded knots of the AHI (9.4, 28.2, 54.4 and 80.2). After integrating the clinical definition and RCS-selected knots, all subjects were regrouped into four AHI severity stages. Following segmented multivariate linear modelling of each stage, distinguishable sets of OSA risk factors were quantified: low-density lipoprotein cholesterol (LDL-C), apolipoprotein E and high-density lipoprotein cholesterol (HDL-C); body mass index and/or waist to hip ratio; and HDL-C, LDL-C and triglycerides were specifically associated with stage I, stages II and III, and stages II-IV with different OSA indices. CONCLUSIONS: Our study revealed the multistage and non-monotonic relationships between OSA and dyslipidaemia and quantified the relationships between OSA severity indexes and distinct risk factors for specific OSA severity stages. Our study suggests that a new interpretive and predictive strategy for dynamic assessment of the risk progression over the clinical course of OSA should be adopted. PMID- 26883676 TI - Observation of the seleno bis-(S-glutathionyl) arsinium anion in rat bile. AB - Certain arsenic and selenium compounds show a remarkable mutual cancelation of toxicities, where a lethal dose of one can be voided by an equimolar and otherwise lethal dose of the other. It is now well established that the molecular basis of this antagonism is the formation and biliary excretion of seleno bis-(S glutathionyl) arsinium anion [(GS)2AsSe](-). Previous work has definitively demonstrated the presence of [(GS)2AsSe](-) in rabbit bile, but only in the presence of other arsenic and selenium species. Rabbits have a gall bladder, which concentrates bile and lowers its pH; it seems likely that this may be responsible for the breakdown of biliary [(GS)2AsSe](-). Since rats have no gall bladder, the bile proceeds directly through the bile duct from the hepatobiliary tree. In the present work we have shown that the primary product of biliary co excretion of arsenic and selenium in rats is [(GS)2AsSe](-), with essentially 100% of the arsenic and selenium present as this species. The chemical plausibility of the X-ray absorption spectroscopy-derived structural conclusions of this novel arsenic and selenium co-excretion product is supported by density functional theory calculations. These results establish the biomolecular basis to further explore the use of selenium dietary supplements as a possible palliative for chronic low-level arsenic poisoning of human populations. PMID- 26883677 TI - Copper-Catalyzed Annulation: A Method for the Systematic Synthesis of Phenanthridinium Bromide. AB - A novel procedure for the Cu-catalyzed systematic synthesis of phenanthridinium bromide is reported. This transformation was achieved with direct construction of central pyridinium core by using an in situ formed biaryl imine as a substrate. Tolerance of a very wide variety of N-substituents is indicated; this has never previously been disclosed by other reports. Application of this method to synthesis of the natural alkaloid bicolorine, and its derivatives, was also carried out in only three synthetic steps from commercially available compounds. PMID- 26883678 TI - Interleukin-17 acts as double-edged sword in anti-tumor immunity and tumorigenesis. AB - Interleukin-17 (IL-17), a proinflammatory cytokine, mainly produced by Th17 cells, participates in both innate and adaptive immune responses and is involved in various diseases, including infectious diseases, autoimmune disorders and cancer. Emerging evidence indicates that IL-17 not only has an oncogenic role in tumorigenesis by regulating tumor angiogenesis and enhancing tumor immune evasion but also exerts anti-tumor functions by enhancing natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) activation and through the recruitment of neutrophils, NK cells and CD4+ and CD8+ T cells to tumor tissue. In this review, we provide an overview on the basic biology of IL-17 and recent findings regarding its enigmatic double-edged features in tumorigenesis, with special attention to the roles of IL-17 produced by tumor cells interacting with other factors in the tumor microenvironment. PMID- 26883680 TI - Natural killer cell adoptive immunotherapy: Coming of age. AB - Cell therapy is a promising alternative to harsh chemotherapy and radiation therapy for cancer. Natural killer (NK) cells in particular have great potential for direct use in adoptive immunotherapy (AI) for cancer and to improve the graft vs-leukemia (GVL) effect of hematopoietic stem cell transplants (HSCTs). NK cell number and function are associated with a strong GVL effect without inducing graft-versus-host disease in most settings. Clinical trials demonstrating the therapeutic role of NK cells in HSCT recipients or testing the safety and efficacy of AI with NK cells have been primarily directed at treating acute myeloid leukemia, although investigators have used NK cells for treatment of other hematological diseases, sarcomas, carcinomas, and brain tumors. Major challenges must be overcome in making NK cell-based therapy cost-effective, the most important being the need to collect or generate an adequate number of effector cells. In this review, we discuss protocols for isolation, expansion, and in vitro propagation of large quantities of functional NK cells that meet the criteria for clinical applications. Among the methods described are the use of bioreactors for scaling up production and expansion of NK cells in the presence of interleukins and feeder cells. We also discuss novel methodologies that optimize the generation of clinical grade NK-cell products for AI. PMID- 26883679 TI - Hip Fracture Surgery and Survival in Centenarians. AB - BACKGROUND: Hip fracture (HF) is increasingly frequent with advancing age. Studies describing the HF incidence rate and survival after surgery in centenarians are scanty. To fill this gap, we performed a large population-based investigation on Lombardy centenarians (Italy). METHODS: Retrospective observational cohort study based on information from the Healthcare Utilization Database. Among the cohort of 7,830 residents that reached 100 years of age between 2004 and 2011, incidence rate of HF was calculated. Two hundred fifty nine patients were discharged alive from a hospital after HF and surgical repair (HF cohort). For each HF cohort member, a control was randomly selected from the initial cohort to be matched for gender and date of birth, and who did not experience HF from the date of their hundredth birthday until the date of hospital discharge of the corresponding HF cohort member. The survival curves and the hazard functions of HF and control cohort were calculated within 2 years. RESULTS: Over a mean follow-up of 1.85 years, HF incidence rate was 23.1 per 1,000 centenarians per year. Survival probability was significantly lower in HF cohort than in control cohort (31.5 vs 48.1%, p < .001). Hazard functions showed an increased risk of death in HF cohort than in control cohort, especially in the 3 months after surgery. CONCLUSION: Survival analysis exhibited an excess mortality in the first 3 months among HF cohort members, but not beyond this period. Every effort to counteract HF is warranted, including prevention of falls and high quality of care, especially in the early postsurgical time. PMID- 26883681 TI - Increased soluble CD72 in systemic lupus erythematosus is in association with disease activity and lupus nephritis. AB - INTRODUCTION: B cell receptor (BCR) -mediated signals are enhanced when CD72 expression is deficient on B cells in autoimmune diseases. The significance of soluble CD72 (sCD72) has not been elucidated. METHODS: Soluble CD72 was analyzed in the serum of 159 SLE patients, 40 rheumatoid arthritis (RA) patients, and 100 healthy individuals. Correlations between sCD72 and SLE disease activity (SLEDAI) were assessed. RESULTS: Soluble CD72 was found increased in SLE patients, when compared to both RA patients and healthy individuals (20.2 +/- 1.2 ng/ml; 10.6 +/ 4.6 ng/ml and 7.2 +/- 3.3 ng/ml; p < 0.001). Soluble CD72 level was significantly higher in SLE patients with renal involvement than in patients without (31.8 +/- 2.3 ng/ml vs 13.9 +/- 0.9 ng/ml; p < 0.001) and also with the presence of auto-antibodies. CONCLUSION: Soluble CD72 is significantly increased in SLE patients mainly in those with renal involvement. Increased sCD72 may become a potential biomarker for renal involvement in SLE. PMID- 26883683 TI - Copper(II) binding properties of hepcidin. AB - Hepcidin is a peptide hormone that regulates the homeostasis of iron metabolism. The N-terminal domain of hepcidin is conserved amongst a range of species and is capable of binding Cu(II) and Ni(II) through the amino terminal copper-nickel binding motif (ATCUN). It has been suggested that the binding of copper to hepcidin may have biological relevance. In this study we have investigated the binding of Cu(II) with model peptides containing the ATCUN motif, fluorescently labelled hepcidin and hepcidin using MALDI-TOF mass spectrometry. As with albumin, it was found that tetrapeptide models of hepcidin possessed a higher affinity for Cu(II) than that of native hepcidin. The log K 1 value of hepcidin for Cu(II) was determined as 7.7. Cu(II) binds to albumin more tightly than hepcidin (log K 1 = 12) and in view of the serum concentration difference of albumin and hepcidin, the bulk of kinetically labile Cu(II) present in blood will be bound to albumin. It is estimated that the concentration of Cu(II)-hepcidin will be less than one femtomolar in normal serum and thus the binding of copper to hepcidin is unlikely to play a role in iron homeostasis. As with albumin, small tri and tetra peptides are poor models for the metal binding properties of hepcidin. PMID- 26883682 TI - A novel gene delivery composite system based on biodegradable folate-poly (ester amine) polymer and thermosensitive hydrogel for sustained gene release. AB - Local anti-oncogene delivery providing high local concentration of gene, increasing antitumor effect and decreasing systemic side effects is currently attracting interest in cancer therapy. In this paper, a novel local sustained anti-oncogene delivery system, PECE thermoresponsive hydrogel containing folate poly (ester amine) (FA-PEA) polymer/DNA (tumor suppressor) complexes, is demonstrated. First, a tumor-targeted biodegradable folate-poly (ester amine) (FA PEA) polymer based on low-molecular-weight polyethyleneimine (PEI) was synthesized and characterized, and the application for targeted gene delivery was investigated. The polymer had slight cytotoxicity and high transfection efficiency in vitro compared with PEI 25k, which indicated that FA-PEA was a potential vector for targeted gene delivery. Meanwhile, we successfully prepared a thermoresponsive PECE hydrogel composite containing FA-PEA/DNA complexes which could contain the genes and slowly release the genes into cells. We concluded the folate-poly (ester amine) (FA-PEA) polymer would be useful for targeted gene delivery, and the novel gene delivery composite based on biodegradable folate poly (ester amine) polymer and thermosensitive PECE hydrogel showed potential for sustained gene release. PMID- 26883684 TI - The impact of violence on sex risk and drug use behaviors among women engaged in sex work in Phnom Penh, Cambodia. AB - BACKGROUND: Violence, substance use, and HIV disproportionately impact female entertainment and sex workers (FESW), but causal pathways remain unclear. METHODS: We examined data from an observational cohort of FESW age 15-29 in Phnom Penh, Cambodia for associations between violence exposure and sexual risk and drug use. Validated measures of physical and sexual violence were assessed at baseline. Self-reported outcomes measured quarterly over the next 12-months included past month sexual partners, consistent condom use by partner type, sex while high, and amphetamine type stimulant (ATS) use. Biomarkers measured quarterly included prostate specific antigen (PSA) and urine toxicology. Generalized estimating equations were fit adjusting for age, education, marital status and sex work venue. RESULTS: Of 220 women, 48% reported physical or sexual violence in the preceding 12-months. Physical violence was associated with increased number of sex partners (adjusted incidence rate ratio [aIRR] 1.33; 95% CI: 1.04-1.71), greater odds of sex while high (adjusted odds ratio [aOR] 2.42; 95% CI: 1.10-5.33), increased days of ATS use (aIRR 2.74; 95% CI: 1.29-5.84) and increased odds of an ATS+ urine screen (aOR 2.80, 95%CI: 1.38-5.66). Sexual violence predicted decreased odds of consistent condom use with non-paying partners (aOR 0.24; 95% CI: 0.10-0.59) and greater odds of a PSA+ vaginal swab (aOR 1.83; 95% CI: 1.13-2.93). CONCLUSIONS: Physical and sexual violence are prevalent among Cambodian FESW and associated with subsequent sexual risk and drug use behaviors. Clinical research examining interventions targeting structural and interpersonal factors impacting violence is needed to optimize HIV/AIDS prevention among FESW. PMID- 26883686 TI - Production of recombinant insulin-like androgenic gland hormones from three decapod species: In vitro testicular phosphorylation and activation of a newly identified tyrosine kinase receptor from the Eastern spiny lobster, Sagmariasus verreauxi. AB - In crustaceans the insulin-like androgenic gland hormone (IAG) is responsible for male sexual differentiation. To date, the biochemical pathways through which IAG exerts its effects are poorly understood and could be elucidated through the production of a functional recombinant IAG (rIAG). We have successfully expressed glycosylated, biologically active IAG using the Pichia pastoris yeast expression system. We co-expressed recombinant single-chain precursor molecules consisting of the B and A chains (the mature hormone) tethered by a flexible linker, producing rIAGs of the following commercially important species: Eastern spiny lobster Sagmariasus verreauxi (Sv), redclaw crayfish Cherax quadricarinatus (Cq) and giant freshwater prawn Macrobrachium rosenbergii (Mr). We then tested the biological activity of each, through the ability to increase phosphorylation in the testis; both Sv and Cq rIAGs significantly elevated phosphorylation specific to their species, and in a dose-dependent manner. Mr rIAG was tested on Macrobrachium australiense (Ma), eliciting a similar response. Moreover, using bioinformatics analyses of the de novo assembled spiny lobster transcriptome, we identified a spiny lobster tyrosine kinase insulin receptor (Sv-TKIR). We validated this discovery with a receptor activation assay in COS-7 cells expressing Sv-TKIR, using a reporter SRE-LUC system designed for RTKs, with each of the rIAG proteins acting as the activation ligand. Using recombinant proteins, we aim to develop specific tools to control sexual development through the administration of IAG within the critical sexual differentiation time window. The biologically active rIAGs generated might facilitate commercially feasible solutions for the long sought techniques for sex-change induction and monosex population culture in crustaceans and shed new light on the physiological mode of action of IAG in crustaceans. PMID- 26883687 TI - Time-course changes in muscle protein degradation in heat-stressed chickens: Possible involvement of corticosterone and mitochondrial reactive oxygen species generation in induction of the ubiquitin-proteasome system. AB - Heat stress (HS) induces muscle protein degradation as well as production of mitochondrial reactive oxygen species (ROS). In the present study, to improve our understanding of how protein degradation is induced by HS treatment in birds, a time course analysis of changes in the circulating levels of glucocorticoid and N(tau)-methylhistidine, muscle proteolysis-related gene expression, and mitochondrial ROS generation, was conducted. At 25 days of age, chickens were exposed to HS conditions (33 degrees C) for 0, 0.5, 1 or 3 days. While no alteration in plasma N(tau)-methylhistidine concentration relative to that of the control group was observed in the 0.5 day HS group, the concentration was significantly higher in the 3-d HS treatment group. Plasma corticosterone concentrations increased in response to 0.5-d HS treatment, but subsequently returned to near-normal values. HS treatment for 0.5 days did not change the levels of MU-calpain, cathepsin B, or proteasome C2 subunit mRNA, but increased the levels of mRNA encoding atrogin-1 (P<0.05) and its transcription factor, forkhead box O3 (P=0.09). Under these hyperthermic conditions, mitochondrial superoxide production was significantly increased than that of thermoneutral control. Here, we show that HS-induced muscle protein degradation may be due to the activation of ubiquitination by atrogin-1, and that this process may involve mitochondrial ROS production as well as corticosterone secretion. PMID- 26883685 TI - Detection of "bath salts" and other novel psychoactive substances in hair samples of ecstasy/MDMA/"Molly" users. AB - BACKGROUND: Ecstasy (MDMA) in the US is commonly adulterated with other drugs, but research has not focused on purity of ecstasy since the phenomenon of "Molly" (ecstasy marketed as pure MDMA) arose in the US. METHODS: We piloted a rapid electronic survey in 2015 to assess use of novel psychoactive substances (NPS) and other drugs among 679 nightclub/festival-attending young adults (age 18-25) in New York City. A quarter (26.1%) of the sample provided a hair sample to be analyzed for the presence of select synthetic cathinones ("bath salts") and some other NPS. Samples were analyzed using fully validated UHPLC-MS/MS methods. To examine consistency of self-report, analyses focused on the 48 participants with an analyzable hair sample who reported lifetime ecstasy/MDMA/Molly use. RESULTS: Half (50.0%) of the hair samples contained MDMA, 47.9% contained butylone, and 10.4% contained methylone. Of those who reported no lifetime use of "bath salts", stimulant NPS, or unknown pills or powders, about four out of ten (41.2%) tested positive for butylone, methylone, alpha-PVP, 5/6-APB, or 4-FA. Racial minorities were more likely to test positive for butylone or test positive for NPS after reporting no lifetime use. Frequent nightclub/festival attendance was the strongest predictor of testing positive for MDMA, butylone, or methylone. DISCUSSION: Results suggest that many ecstasy-using nightclub/festival attendees may be unintentionally using "bath salts" or other NPS. Prevention and harm reduction education is needed for this population and "drug checking" (e.g., pill testing) may be beneficial for those rejecting abstinence. PMID- 26883688 TI - The concomitant use of fesoterodine and topical vaginal estrogen in the management of overactive bladder and sexual dysfunction in postmenopausal women. AB - OBJECTIVE: The objective of this study is to investigate the combination effect of anti-muscarinic medication and topical vaginal estrogen in the treatment of overactive bladder (OAB) and female sexual dysfunction in postmenopausal women. STUDY DESIGN: After IRB approval, 23 female subjects who met the entry criteria were randomized into two groups: (1) fesoterodine (Toviaz(r), Pfizer, NY) with topical vaginal estrogen (Premarin(r), Pfizer, NY) once daily or (2) fesoterodine once daily alone. If 4 mg fesoterodine was tolerated at 1-week, the dose was increased to 8 mg. MAIN OUTCOME MEASURES: Primary endpoints were improvement in OAB symptom severity (Overactive Bladder Questionnaire, OAB-Q SF), improvement in OAB health-related quality of life (HRQL) (OAB-Q SF), and sexual function (Sexual Quality of Life-Female, SQOL-F) after 12 weeks. Secondary endpoint was change in total number of micturitions. RESULTS: After 12-weeks, the combination group had a significant improvement in OAB symptom severity (p = 0.006), HRQL (p = 0.029), and SQOL-F (0.0003). The fesoterodine alone group also had significant improvement in OAB symptom severity (p < 0.0001), HRQL (p = 0.0002), and SQOL-F (p = 0.02). When compared directly to the fesoterodine alone group, the combination group after 12-weeks had a reduced OAB symptom severity (10 versus 23.3; p = 0.35), higher HRQL (96.9 versus 84.6; p = 0.75), and higher SQOL-F (99 versus 81; p = 0.098). The total number of micturitions over 3 d was significantly reduced in the combination group (45-26, p = 0.03) between baseline and 12-weeks. CONCLUSIONS: The combined effect of fesoterodine and topical vaginal estrogen improved OAB symptoms and sexual function in postmenopausal women. PMID- 26883689 TI - Oxytocin improves cytological and histological profiles of vaginal atrophy in postmenopausal women. AB - OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks. RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04). CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells. PMID- 26883690 TI - Direct Difluoromethylation of Aryl Halides via Base Metal Catalysis at Room Temperature. AB - A stable and isolable difluoromethyl zinc reagent has been prepared through the reaction of ICF2H with diethyl zinc and DMPU. This new zinc reagent is a free flowing solid and can be used in combination with a nickel catalyst to difluoromethylate aryl iodides, bromides, and triflates at room temperature. Such mild conditions for the catalytic difluoromethylation of these substrates are unprecedented. PMID- 26883692 TI - Early Cretaceous paleomagnetic and geochronologic results from the Tethyan Himalaya: Insights into the Neotethyan paleogeography and the India-Asia collision. AB - To better understand the Neotethyan paleogeography, a paleomagnetic and geochronological study has been performed on the Early Cretaceous Sangxiu Formation lava flows, which were dated from ~135.1 Ma to ~124.4 Ma, in the Tethyan Himalaya. The tilt-corrected site-mean characteristic remanent magnetization (ChRM) direction for 26 sites is Ds = 296.1 degrees , Is = -65.7 degrees , ks = 51.7, alpha95 = 4.0 degrees , corresponding to a paleopole at 5.9 degrees S, 308.0 degrees E with A95 = 6.1 degrees . Positive fold and reversal tests prove that the ChRM directions are prefolding primary magnetizations. These results, together with reliable Cretaceous-Paleocene paleomagnetic data observed from the Tethyan Himalaya and the Lhasa terrane, as well as the paleolatitude evolution indicated by the apparent polar wander paths (APWPs) of India, reveal that the Tethyan Himalaya was a part of Greater India during the Early Cretaceous (135.1-124.4 Ma) when the Neotethyan Ocean was up to ~6900 km, it rifted from India sometime after ~130 Ma, and that the India-Asia collision should be a dual collision process including the first Tethyan Himalaya-Lhasa terrane collision at ~54.9 Ma and the final India-Tethyan Himalaya collision at ~36.7 Ma. PMID- 26883691 TI - Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments. AB - Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4 trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID- 26883693 TI - Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents. AB - We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum plasma concentration and area under the concentration versus time curve from 0 to 24 h were 0.74 MUg/ml (0.61 MUg/ml) and 9.28 MUg . h/ml (6.30 MUg . h/ml), respectively. The exposure and safety in this small cohort of adolescents were comparable to those for adults. (This study has been registered at ClinicalTrials.gov under registration no. NCT01966055.). PMID- 26883694 TI - Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections. AB - Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem susceptible A. baumannii In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems. PMID- 26883696 TI - Occurrence of the Plasmid-Borne mcr-1 Colistin Resistance Gene in Extended Spectrum-beta-Lactamase-Producing Enterobacteriaceae in River Water and Imported Vegetable Samples in Switzerland. PMID- 26883697 TI - Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro. AB - Thein vitroactivities of clarithromycin and tigecycline alone and in combination againstMycobacterium aviumwere assessed. The activity of clarithromycin was time dependent, highly variable, and often resulted in clarithromycin resistance. Tigecycline showed concentration-dependent activity, and mycobacterial killing could only be achieved at high concentrations. Tigecycline enhanced clarithromycin activity againstM. aviumand prevented clarithromycin resistance. Whether there is clinical usefulness of tigecycline in the treatment ofM. aviuminfections needs further study. PMID- 26883695 TI - Phenotypically Adapted Mycobacterium tuberculosis Populations from Sputum Are Tolerant to First-Line Drugs. AB - Tuberculous sputum contains multipleMycobacterium tuberculosispopulations with different requirements for isolationin vitro These include cells that form colonies on solid media (plateableM. tuberculosis), cells requiring standard liquid medium for growth (nonplateableM. tuberculosis), and cells requiring supplementation of liquid medium with culture supernatant (SN) for growth (SN dependentM. tuberculosis). Here, we describe protocols for the cryopreservation and direct assessment of antimicrobial tolerance of theseM. tuberculosispopulations within sputum. Our results show that first-line drugs achieved only modest bactericidal effects on all three populations over 7 days (1 to 2.5 log10reductions), and SN-dependentM. tuberculosiswas more tolerant to streptomycin and isoniazid than the plateable and nonplateableM. tuberculosisstrains. Susceptibility of plateableM. tuberculosisto bactericidal drugs was significantly increased after passagein vitro; thus, tolerance observed in the sputum samples from the population groups was likely associated with mycobacterial adaptation to the host environment at some time prior to expectoration. Our findings support the use of a simpleex vivosystem for testing drug efficacies against mycobacteria that have phenotypically adapted during tuberculosis infection. PMID- 26883698 TI - Benznidazole Extended-Release Tablets for Improved Treatment of Chagas Disease: Preclinical Pharmacokinetic Study. AB - Benznidazole (BNZ) is the first-line drug for the treatment of Chagas disease. The drug is available in the form of immediate-release tablets for 100-mg (adult) and 12.5-mg (pediatric) doses. The drug is administered two or three times daily for 60 days. The high frequency of daily administrations and the long period of treatment are factors that significantly contribute to the abandonment of therapy, affecting therapeutic success. Accordingly, this study aimed to evaluate the preclinical pharmacokinetics of BNZ administered as extended-release tablets (200-mg dose) formulated with different types of polymers (hydroxypropyl methylcellulose K4M and K100M), compared to the tablets currently available. The studies were conducted with rabbits, and BNZ quantification was performed in plasma and urine by ultraperformance liquid chromatography methods previously validated. The bioavailability of BNZ was adequate in the administration of extended-release tablets; however, with the administration of the pediatric tablet, the bioavailability was lower than with other tablets, which showed that the clinical use of this formulation should be monitored. The pharmacokinetic parameters demonstrated that the extended-release tablets prolonged drug release from the pharmaceutical matrix and provided an increase in the maintenance of the drug concentrationin vivo, which would allow the frequency of administration to be reduced. Thus, a relative bioavailability study in humans will be planned for implementation of a new product for the treatment of Chagas disease. PMID- 26883699 TI - Identification of Synthetic and Natural Host Defense Peptides with Leishmanicidal Activity. AB - Leishmaniaparasites are a major public health problem worldwide. Effective treatment of leishmaniasis is hampered by the high incidence of adverse effects to traditional drug therapy and the emergence of resistance to current therapeutics. A vaccine is currently not available. Host defense peptides have been investigated as novel therapeutic agents against a wide range of pathogens. Here we demonstrate that the antimicrobial peptide LL-37 and the three synthetic peptides E6, L-1018, and RI-1018 exhibit leishmanicidal activity against promastigotes and intramacrophage amastigotes ofLeishmania donovaniandLeishmania major We also report that theLeishmaniaprotease/virulence factor GP63 confers protection toLeishmaniafrom the cytolytic properties of alll-form peptides (E6, L 1018, and LL-37) but not thed-form peptide RI-1018. The results suggest that RI 1018, E6, and LL-37 are promising peptides to develop further into components for antileishmanial therapy. PMID- 26883700 TI - Preventing Implant-Associated Infections by Silver Coating. AB - Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum dependent activity againstStaphylococcus epidermidisandStaphylococcus aureusin an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 * 10(6)CFU ofS. epidermidisper cage. InS. aureusinfections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not preventS. aureusinfections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistantS. aureusinfections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 MUg Ag/ml was reached in the cage fluid, corresponding to almost 6* the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application. PMID- 26883701 TI - Comparative Study of Activities of a Diverse Set of Antimycobacterial Agents against Mycobacterium tuberculosis and Mycobacterium ulcerans. AB - A library of compounds covering a broad chemical space was selected from a tuberculosis drug development program and was screened in a whole-cell assay against Mycobacterium ulcerans, the causative agent of the necrotizing skin disease Buruli ulcer. While a number of potent antitubercular agents were only weakly active or inactive against M. ulcerans, five compounds showed high activity (90% inhibitory concentration [IC90], <=1 MUM), making screening of focused antitubercular libraries a good starting point for lead generation against M. ulcerans. PMID- 26883703 TI - Pharmacokinetics and Concentration-Dependent Efficacy of Isavuconazole for Treatment of Experimental Invasive Pulmonary Aspergillosis. AB - We studied the pharmacokinetics and efficacy of the broad-spectrum triazole isavuconazole for the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Treatment started 24 h after endotracheal administration of Aspergillus fumigatus inoculum; study subjects included rabbits receiving orally administered prodrug isavuconazonium sulfate (BAL8557) equivalent to active moiety isavuconazole (ISA; BAL4815) at 20 (ISA20), 40 (ISA40), and 60 (ISA60) mg/kg (of body weight)/day, with an initial loading dose of 90 mg/kg (ISA90), and untreated rabbits (UC). There were significant concentration-dependent reductions of residual fungal burden (log CFU/gram) and of organism-mediated pulmonary injury, lung weights, and pulmonary infarct scores in ISA40- and ISA60-treated rabbits in comparison to those of UC (P < 0.001). ISA20-treated (P < 0.05), ISA40-treated, and ISA60-treated (P < 0.001) rabbits demonstrated significantly prolonged survival in comparison to that of UC. ISA40- and ISA60-treated animals demonstrated a significant decline of serum (1->3)-beta d-glucan levels (P < 0.05) and galactomannan indices (GMIs) during therapy following day 4 in comparison to progressive GMIs of UC (P < 0.01). There also were significantly lower concentration-dependent GMIs in bronchoalveolar lavage (BAL) fluid from ISA40- and ISA60-treated rabbits (P < 0.001). There was a direct correlation between isavuconazole plasma area under the concentration-time curve from 0 to 24 h (AUC0-24) and residual fungal burdens in lung tissues, pulmonary infarct scores, and total lung weights. In summary, rabbits treated with isavuconazole at 40 and 60 mg/kg/day demonstrated significant dose-dependent reduction of residual fungal burden, decreased pulmonary injury, prolonged survival, lower GMIs in serum and BAL fluid, and lower serum (1->3)-beta-d-glucan levels. PMID- 26883704 TI - Susceptibility of Multidrug-Resistant Gram-Negative Urine Isolates to Oral Antibiotics. AB - Increasing resistance among Gram-negative uropathogens limits treatment options, and susceptibility data for multidrug-resistant isolates are limited. We assessed the activity of five oral agents against 91 multidrug-resistant Gram-negative urine isolates that were collected from emergency department/hospitalized patients. Fosfomycin and nitrofurantoin were most active (>75% susceptibility). Susceptibilities to sulfamethoxazole-trimethoprim, ciprofloxacin, and ampicillin were <=40%; empirical use of these agents likely provides inadequate coverage in areas with a high prevalence of multidrug-resistant uropathogens. PMID- 26883702 TI - Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9. AB - In our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroom Astraeus hygrometricus (Pers.) Morgan, induced reactive oxygen species, leading to apoptosis in Leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 MUg/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity in vitro and in vivo Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by in vitro assay in the presence of a TLR9 agonist and antagonist and by in silico modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of L. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by in silico evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden in vivo by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance in vitro and in vivo. PMID- 26883705 TI - Carbapenem- and Colistin-Resistant Enterobacter cloacae from Delta, Colorado, in 2015. AB - Resistance to carbapenems in Enterobacteriaceae is a clinical problem of growing significance. Difficulty in treating multidrug-resistant Gram-negative organisms with conventional antibiotics has led to a renewed and increasing use of polymyxin compounds, such as colistin. Here, we report the isolation of carbapenem- and colistin-resistant Enterobacter cloacae from a polymicrobial lower extremity wound in an ambulatory patient. Whole-genome sequencing demonstrated the presence of chromosomal blaIMI-1 and blaAmpC, as well as numerous efflux pump genes. PMID- 26883706 TI - Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM beta-Lactamases. AB - The Lactamase Engineering Database (www.LacED.uni-stuttgart.de) was developed to facilitate the classification and analysis of TEM beta-lactamases. The current version contains 474 TEM variants. Two hundred fifty-nine variants form a large scale-free network of highly connected point mutants. The network was divided into three subnetworks which were enriched by single phenotypes: one network with predominantly 2be and two networks with 2br phenotypes. Fifteen positions were found to be highly variable, contributing to the majority of the observed variants. Since it is expected that a considerable fraction of the theoretical sequence space is functional, the currently sequenced 474 variants represent only the tip of the iceberg of functional TEM beta-lactamase variants which form a huge natural reservoir of highly interconnected variants. Almost 50% of the variants are part of a quartet. Thus, two single mutations that result in functional enzymes can be combined into a functional protein. Most of these quartets consist of the same phenotype, or the mutations are additive with respect to the phenotype. By predicting quartets from triplets, 3,916 unknown variants were constructed. Eighty-seven variants complement multiple quartets and therefore have a high probability of being functional. The construction of a TEM beta-lactamase network and subsequent analyses by clustering and quartet prediction are valuable tools to gain new insights into the viable sequence space of TEM beta-lactamases and to predict their phenotype. The highly connected sequence space of TEM beta-lactamases is ideally suited to network analysis and demonstrates the strengths of network analysis over tree reconstruction methods. PMID- 26883707 TI - Longitudinal Analysis of the Effect of Inflammation on Voriconazole Trough Concentrations. AB - Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations. In this study, we explored the association between inflammation, reflected by the C reactive protein (CRP) concentration, and VCZ trough concentrations over time. A retrospective analysis of data was performed for patients with more than one steady-state VCZ trough concentration and a CRP concentration measured on the same day. A longitudinal analysis was used for series of observations obtained from many study participants over time. The approach involved inclusion of random effects and autocorrelation in linear models to reflect within-person cross-time correlation. A total of 50 patients were eligible for the study, resulting in 139 observations (paired VCZ and CRP concentrations) for the analysis, ranging from 2 to 6 observations per study participant. Inflammation, marked by the CRP concentration, had a significant association with VCZ trough concentrations (P < 0.001). Covariates such as age and interacting comedication ([es]omeprazole), also showed a significant correlation between VCZ and CRP concentrations (P < 0.05). The intrapatient variation of trough concentrations of VCZ was 1.401 (confidence interval [CI], 0.881 to 2.567), and the interpatient variation was 1.756 (CI, 0.934 to 4.440). The autocorrelation between VCZ trough concentrations at two sequential time points was calculated at 0.71 (CI, 0.51 to 0.92). The inflammatory response appears to play a significant role in the largely unpredictable pharmacokinetics of VCZ, especially in patients with high inflammatory response, as reflected by high CRP concentrations. PMID- 26883708 TI - Kinetic Studies on CphA Mutants Reveal the Role of the P158-P172 Loop in Activity versus Carbapenems. AB - Site-directed mutagenesis of CphA indicated that prolines in the P158-P172 loop are essential for the stability and the catalytic activity of subclass B2 metallo beta-lactamases against carbapenems. The sequential substitution of proline led to a decrease of the catalytic efficiency of the variant compared to the wild type (WT) enzyme but also to a higher affinity for the binding of the second zinc ion. PMID- 26883710 TI - First Description of IncX3 Plasmids Carrying blaOXA-181 in Escherichia coli Clinical Isolates in Burkina Faso. PMID- 26883709 TI - Increasing Experience with Primary Oral Medical Therapy for Mycobacterium ulcerans Disease in an Australian Cohort. AB - Buruli ulcer (BU) is a necrotizing infection of subcutaneous tissue that is caused by Mycobacterium ulcerans and is responsible for disfiguring skin lesions. The disease is endemic to specific geographic regions in the state of Victoria in southeastern Australia. Growing evidence of the effectiveness of antibiotic therapy for M. ulcerans disease has evolved our practice to the use of primarily oral medical therapy. An observational cohort study was performed on all confirmed M. ulcerans cases treated with primary rifampin-based medical therapy at Barwon Health between October 2010 and December 2014 and receiving 12 months of follow-up. One hundred thirty-two patients were managed with primary medical therapy. The median age of patients was 49 years, and nearly 10% had diabetes mellitus. Lesions were ulcerative in 83.3% of patients and at WHO stage 1 in 78.8% of patients. The median duration of therapy was 56 days, with 22 patients (16.7%) completing fewer than 56 days of antimicrobial treatment. Antibiotic associated complications requiring cessation of one or more antibiotics occurred in 21 (15.9%) patients. Limited surgical debridement was performed on 30 of these medically managed patients (22.7%). Cure was achieved, with healing within 12 months, in 131 of 132 patients (99.2%), and cosmetic outcomes were excellent. Primary rifampin-based oral medical therapy for M. ulcerans disease, combined with either clarithromycin or a fluoroquinolone, has an excellent rate of cure and an acceptable toxicity profile in Australian patients. We advocate for further research to determine the optimal and safest minimum duration of medical therapy for BU. PMID- 26883711 TI - A New Antileishmanial Preparation of Combined Solamargine and Solasonine Heals Cutaneous Leishmaniasis through Different Immunochemical Pathways. AB - Little has been done during the past 100 years to develop new antileishmanial drugs. Most infected individuals live in poor countries and have a low cash income to be attractive targets to pharmaceutical corporations. Two heterosidic steroids, solamargine and solasonine, initially identified as major components of the Brazilian plant Solanum lycocarpum, were tested for leishmanicidal activity. Both alkaloids killed intracellular and extracellular Leishmania mexicana parasites more efficiently than the reference drug sodium stibogluconate. A total of 10 MUM each individual alkaloid significantly reduced parasite counts in infected macrophages and dendritic cells. In vivo treatment of C57BL/6 mice with a standardized topical preparation containing solamargine (45.1%) and solasonine (44.4%) gave significant reductions in lesion sizes and parasite counts recovered from lesions. Alkaloids present different immunochemical pathways in macrophages and dendritic cells. We conclude that this topical preparation is effective and a potential new and inexpensive treatment for cutaneous leishmaniasis. PMID- 26883712 TI - Daptomycin Tolerance in the Staphylococcus aureus pitA6 Mutant Is Due to Upregulation of the dlt Operon. AB - Understanding the mechanisms of how bacteria become tolerant toward antibiotics during clinical therapy is a very important object. In a previous study, we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in the pitA6 mutant differs from classical resistance mechanisms since there is no increase in the MIC. In this follow-up study, we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that 234 genes were at least 2.0-fold differentially expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism, and replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt operon, which is induced by the accumulation of intracellular Pi The GraXRS system, known as an activator of the dlt operon (d-alanylation of teichoic acids) and of the mprF gene (multiple peptide resistance factor), is not involved in DAP tolerance of the pitA6 mutant. In conclusion, DAP tolerance of the pitA6 mutant is due to an upregulation of the dlt operon, triggered directly or indirectly by the accumulation of Pi. PMID- 26883713 TI - Clofazimine Inhibits the Growth of Babesia and Theileria Parasites In Vitro and In Vivo. AB - The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against Babesia bovis, B. bigemina, B. caballi, and Theileria equi in in vitro culture and against Babesia microti in mice. The 50% inhibitory concentrations (IC50s) of clofazimine against the in vitro growth of B. bovis, B. bigemina, B. caballi, and T. equi were 4.5, 3, 4.3, and 0.29 MUM, respectively. In mice infected with B. microti, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed B. microti On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of B. microti was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against Babesia and Theileria in vitro and in vivo, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis. PMID- 26883714 TI - Antibiotic Resistance among Urinary Isolates from Female Outpatients in the United States in 2003 and 2012. AB - A retrospective analysis was performed using The Surveillance Network, USA, to examine the prevalence of antibiotic resistance among urine isolates from U.S. female outpatients in 2012 and assessed trends in antibiotic resistance comparing data from 2003 and 2012. The most common pathogen identified in 2012 (n = 285,325) was Escherichia coli (64.9% of isolates). In 2012, E. coli resistance to nitrofurantoin was low (<3%) across all age groups. E. coli resistance to ciprofloxacin was high among adults (11.8%) and elderly outpatients (29.1%). When comparing the 2003 and 2012 data from isolates from adults, E. coli resistance to nitrofurantoin changed only slightly (from 0.7% to 0.9%), whereas increases in resistance to ciprofloxacin (3.6% to 11.8%) and trimethoprim-sulfamethoxazole (17.2% to 22.2%) changed substantially. In the United States, E. coli has become increasingly resistant to ciprofloxacin and trimethoprim-sulfamethoxazole (TMP SMX) in adult female outpatients. Nitrofurantoin retains high levels of antibiotic activity against urinary E. coli. PMID- 26883715 TI - Metabolomics in diabetes, a review. AB - Metabolomics is a promising approach for the identification of chemical compounds that serve for early detection, diagnosis, prediction of therapeutic response and prognosis of disease. Moreover, metabolomics has shown to increase the diagnostic threshold and prediction of type 2 diabetes. Evidence suggests that branched chain amino acids, acylcarnitines and aromatic amino acids may play an early role on insulin resistance, exposing defects on amino acid metabolism, beta-oxidation, and tricarboxylic acid cycle. This review aims to provide a panoramic view of the metabolic shifts that antecede or follow type 2 diabetes. Key messages BCAAs, AAAs and acylcarnitines are strongly associated with early insulin resistance. Diabetes risk prediction has been improved when adding metabolomic markers of dysglycemia to standard clinical and biochemical factors. PMID- 26883716 TI - MiR-204 inhibits the proliferation and invasion of renal cell carcinoma by inhibiting RAB22A expression. AB - While miR-204 expression may be linked to renal cell carcinoma (RCC) progression, the detailed mechanisms remain unclear. In the present study, we demonstrated that miR-204 was differentially expressed in RCC tissues when compared with surrounding normal kidney tissues. Ectopic overexpression of miR-204 in human RCC cells suppressed cell proliferation and invasion in vitro and in vivo. Mechanism dissection revealed that miR-204 may function through RAB22A signals to inhibit RCC proliferation and invasion. Overexpression of RAB22A by oe-RAB22A was able to partially reverse the miR-204-mediated suppression of RCC tumor progression. Together, these results revealed that miR-204 suppressed RCC proliferation and invasion by directly targeting the RAB22A gene. Targeting newly identified RAB22A with miR-204 may aid in the suppression of RCC proliferation and invasion. PMID- 26883717 TI - Inversion of Spin Signal and Spin Filtering in Ferromagnet|Hexagonal Boron Nitride-Graphene van der Waals Heterostructures. AB - Two dimensional atomically thin crystals of graphene and its insulating isomorph hexagonal boron nitride (h-BN) are promising materials for spintronic applications. While graphene is an ideal medium for long distance spin transport, h-BN is an insulating tunnel barrier that has potential for efficient spin polarized tunneling from ferromagnets. Here, we demonstrate the spin filtering effect in cobalt|few layer h-BN|graphene junctions leading to a large negative spin polarization in graphene at room temperature. Through nonlocal pure spin transport and Hanle precession measurements performed on devices with different interface barrier conditions, we associate the negative spin polarization with high resistance few layer h-BN|ferromagnet contacts. Detailed bias and gate dependent measurements reinforce the robustness of the effect in our devices. These spintronic effects in two-dimensional van der Waals heterostructures hold promise for future spin based logic and memory applications. PMID- 26883718 TI - Enrichment and isolation of Flavobacterium strains with tolerance to high concentrations of cesium ion. AB - Interest in the interaction of microorganisms with cesium ions (Cs(+)) has arisen, especially in terms of their potent ability for radiocesium bioaccumulation and their important roles in biogeochemical cycling. Although high concentrations of Cs(+) display toxic effects on microorganisms, there have been only limited reports for Cs(+)-tolerant microorganisms. Here we report enrichment and isolation of Cs(+)-tolerant microorganisms from soil microbiota. Microbial community analysis revealed that bacteria within the phylum Bacteroidetes, especially Flavobacterium spp., dominated in enrichment cultures in the medium supplemented with 50 or 200 mM Cs(+), while Gammaproteobacteria was dominant in the control enrichment cultures (in the presence of 50 and 200 mM K(+) instead of Cs(+)). The dominant Flavobacterium sp. was successfully isolated from the enrichment culture and was closely related to Flavobacterium chungbukense with 99.5% identity. Growth experiments clearly demonstrated that the isolate has significantly higher tolerance to Cs(+) compared to its close relatives, suggesting the Cs(+)-tolerance is a specific trait of this strain, but not a universal trait in the genus Flavobacterium. Measurement of intracellular K(+) and Cs(+) concentrations of the Cs(+)-tolerant isolate and its close relatives suggested that the ability to maintain low intracellular Cs(+) concentration confers the tolerance against high concentrations of external Cs(+). PMID- 26883719 TI - Critical dependence of magnetostructural coupling and magnetocaloric effect on particle size in Mn-Fe-Ni-Ge compounds. AB - Magnetostructural coupling, which is the coincidence of crystallographic and magnetic transition, has obtained intense attention for its abundant magnetoresponse effects and promising technological applications, such as solid state refrigeration, magnetic actuators and sensors. The hexagonal Ni2In-type compounds have attracted much attraction due to the strong magnetostructural coupling and the resulted giant negative thermal expansion and magnetocaloric effect. However, the as-prepared samples are quite brittle and naturally collapse into powders. Here, we report the effect of particle size on the magnetostructural coupling and magnetocaloric effect in the Ni2In-type Mn-Fe-Ni Ge compound, which undergoes a large lattice change across the transformation from paramagnetic austenite to ferromagnetic martensite. The disappearance of martensitic transformation in a large amount of austenitic phase with reducing particle size, to our best knowledge, has not been reported up to now. The ratio can be as high as 40.6% when the MnNi0.8Fe0.2Ge bulk was broken into particles in the size range of 5~15 MUm. Meanwhile, the remained magnetostructural transition gets wider and the magnetic hysteresis becomes smaller. As a result, the entropy change drops, but the effective cooling power RCeffe increases and attains to the maximum at particles in the range of 20~40 MUm. These observations provide constructive information and highly benefit practical applications for this class of novel magnetoresponse materials. PMID- 26883722 TI - Preface: ACS Applied Materials & Interfaces in China Forum. PMID- 26883720 TI - A minimal conformational switching-dependent model for amyloid self-assembly. AB - Amyloid formation is associated with various pathophysiological conditions like Alzheimer's and Parkinson's diseases as well as many useful functions. The hallmark of amyloid assemblies is a conformational transition of the constituent proteins into a beta - sheet rich filament. Accounting for this conformational transition in amyloidogenic proteins, we develop an analytically solvable model that can probe the dynamics of an ensemble of single filaments. Using the theory and Monte Carlo simulations, we show the presence of two kinetic regimes for the growth of a self-assembling filament - switching-dependent and -independent growth regimes. We observe a saturation in fibril elongation velocities at higher concentrations in the first regime, providing a novel explanation to the concentration-independence of growth velocities observed experimentally. We also compute the length fluctuation of the filaments to characterize aggregate heterogeneity. From the early velocities and length fluctuation, we propose a novel way of estimating the conformational switching rate. Our theory predicts a kinetic phase diagram that has three distinct phases - short oligomers/monomers, disordered aggregates and beta-rich filaments. The model also predicts the force generation potential and the intermittent growth of amyloid fibrils evident from single molecular experiments. Our model could contribute significantly to the physical understanding of amyloid aggregation. PMID- 26883721 TI - DNA Hypomethylation Contributes to Genomic Instability and Intestinal Cancer Initiation. AB - Intestinal cancer is a heterogeneous disease driven by genetic mutations and epigenetic changes. Approximately 80% of sporadic colorectal cancers are initiated by mutation and inactivation of the adenomatous polyposis coli (APC) gene, which results in unrestrained intestinal epithelial growth and formation of adenomas. Aberrant DNA methylation promotes cancer progression by the inactivation of tumor suppressor genes via promoter methylation. In addition, global DNA hypomethylation is often seen before the formation of adenomas, suggesting that it contributes to neoplastic transformation. Previous studies employed mice with a hypomorphic mutation in DNA methyltransferase 1 (Dnmt1), which exhibited constitutive global DNA hypomethylation and decreased tumorigenesis in the Apc(Min/+) mouse model of intestinal cancer. However, the consequences of intestinal epithelial-specific acute hypomethylation during Apc(Min/+) tumor initiation have not been reported. Using temporally controlled intestinal epithelial-specific gene ablation, we show that total loss of Dnmt1 in the Apc(Min/+) mouse model of intestinal cancer causes accelerated adenoma initiation. Deletion of Dnmt1 precipitates an acute response characterized by hypomethylation of repetitive elements and genomic instability, which surprisingly is followed by remethylation with time. Two months post-Dnmt1 ablation, mice display increased macroadenoma load, consistent with a role for Dnmt1 and DNA methylation in maintaining genomic stability. These data suggest that DNA hypomethylation plays a previously unappreciated role in intestinal adenoma initiation. Cancer Prev Res; 9(7); 534-46. (c)2016 AACRSee related article by Lee and Laird, p. 509. PMID- 26883723 TI - Highly Sensitive Thin-Film Field-Effect Transistor Sensor for Ammonia with the DPP-Bithiophene Conjugated Polymer Entailing Thermally Cleavable tert-Butoxy Groups in the Side Chains. AB - The sensing and detection of ammonia have received increasing attention in recent years because of the growing emphasis on environmental and health issues. In this paper, we report a thin-film field-effect transistor (FET)-based sensor for ammonia and other amines with remarkable high sensitivity and satisfactory selectivity by employing the DPP-bithiophene conjugated polymer pDPPBu-BT in which tert-butoxycarboxyl groups are incorporated in the side chains. This polymer thin film shows p-type semiconducting property. On the basis of TGA and FT-IR analysis, tert-butoxycarboxyl groups can be transformed into the -COOH ones by eliminating gaseous isobutylene after thermal annealing of pDPPBu-BT thin film at 240 degrees C. The FET with the thermally treated thin film of pDPPBu-BT displays remarkably sensitive and selective response toward ammonia and volatile amines. This can be attributed to the fact that the elimination of gaseous isobutylene accompanies the formation of nanopores with the thin film, which will facilitate the diffusion and interaction of ammonia and other amines with the semiconducting layer, leading to high sensitivity and fast response for this FET sensor. This FET sensor can detect ammonia down to 10 ppb and the interferences from other volatile analytes except amines can be negligible. PMID- 26883724 TI - IL-4-producing ILC2s are required for the differentiation of TH2 cells following Heligmosomoides polygyrus infection. AB - Immunity to many human and murine gastrointestinal helminth parasites requires interleukin-4 (IL-4)-directed type 2 helper (TH2) differentiation of CD4+ T cells to elicit type-2 immunity. Despite a good understanding of the inflammatory cascade elicited following helminth infection, the initial source of IL-4 is unclear. Previous studies using the rat helminth parasite Nippostronglyus brasiliensis, identified an important role for basophil-derived IL-4 for TH2 differentiation. However, basophils are redundant for TH2 differentiation following infection with the natural helminth parasite of mice Heligmosomoides polygyrus, indicating that other sources of IL-4 are required. In this study using H. polygyrus, which is controlled by IL-4-dependent immunity, we identified that group-2 innate lymphoid cells (ILC2s) produced significant amounts of IL-4 and IL-2 following H. polygyrus infection. Leukotriene D4 was sufficient to stimulate IL-4 secretion by ILC2s, and the supernatant from activated ILC2s could potently drive TH2 differentiation in vitro in an IL-4-dependent manner. Furthermore, specific deletion of IL-4 from ILC2s compromised TH2 differentiation in vivo. Overall, this study highlights a previously unrecognized and important role for ILC2-derived IL-4 for TH2 differentiation in a natural TH2-dependent model of human helminthiasis. PMID- 26883725 TI - T-bet expression by Th cells promotes type 1 inflammation but is dispensable for colitis. AB - The transcription factor T-bet is highly expressed by Th cells isolated from the inflamed intestine of Crohn's disease patients, and has been regarded a critical driver of murine T cell-induced colitis. However, we show here that T-bet expression by Th cells is not required for the manifestation of T-cell-induced colitis in the presence of segmented filamentous bacteria and Helicobacter hepaticus. T-bet expression by Th cells controls their survival and localization, their repertoire of chemokine and chemokine receptor expression, the accumulation of monocytes and macrophages in the inflamed colon, and their differentiation to the M1 type, i.e., type 1 inflammation. Nevertheless, T-bet-deficient Th cells efficiently induce colitis, as reflected by weight loss, diarrhea, and colon histopathology. T-bet-deficient Th cells differentiate into Th1/17 cells, able to express IFN-gamma and IL-17A upon restimulation. While neutralization of IL-17A exacerbated colitis induced by wild-type or T-bet-deficient Th cells, neutralization of IFN-gamma completely abolished colitis. PMID- 26883726 TI - The mycotoxin deoxynivalenol facilitates allergic sensitization to whey in mice. AB - Intestinal epithelial stress or damage may contribute to allergic sensitization against certain food antigens. Hence, the present study investigated whether impairment of intestinal barrier integrity by the mycotoxin deoxynivalenol (DON) contributes to the development of whey-induced food allergy in a murine model. C3H/HeOuJ mice, orally exposed to DON plus whey once a week for 5 consecutive weeks, showed whey-specific IgG1 and IgE in serum and an acute allergic skin response upon intradermal whey challenge, although early initiating mechanisms of sensitization in the intestine appeared to be different compared with the widely used mucosal adjuvant cholera toxin (CT). Notably, DON exposure modulated tight junction mRNA and protein levels, and caused an early increase in IL-33, whereas CT exposure affected intestinal gammadelta T cells. On the other hand, both DON- and CT-sensitized mice induced a time-dependent increase in the soluble IL-33 receptor ST2 (IL-1R1) in serum, and enhanced local innate lymphoid cells type 2 cell numbers. Together, these results demonstrate that DON facilitates allergic sensitization to food proteins and that development of sensitization can be induced by different molecular mechanisms and local immune responses. Our data illustrate the possible contribution of food contaminants in allergic sensitization in humans. PMID- 26883727 TI - CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6 CCL20 axis in treated HIV-1-infected individuals. AB - The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor beta (TGF-beta) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals. PMID- 26883729 TI - Migration of phospholipid vesicles in response to OH(-) stimuli. AB - We demonstrate migration of phospholipid vesicles in response to a pH gradient. Upon simple micro-injection of a NaOH solution, the vesicles linearly moved to the tip of the micro-pipette and the migration velocity was proportional to the gradient of OH(-) concentration. Vesicle migration was characteristic of OH(-) ions and no migration was observed for monovalent salts or nonionic sucrose solutions. The migration of vesicles is quantitatively described by the surface tension gradient model where the hydrolysis of the phospholipids by NaOH solution decreases the surface tension of the vesicle. The vesicles move toward a direction where the surface energy decreases. Thus the chemical modification of lipids produces a mechanical force to drive vesicles. PMID- 26883730 TI - Bathhouse distribution of HIV self-testing kits reaches diverse, high-risk population. AB - We distributed free OraQuick In-home HIV Test(r) kits to men at a gay bathhouse. Men were systematically selected to receive a coupon, which could be redeemed that night for an HIV self-testing kit. Those offered the coupon were asked to take an 11-item survey. About 181 men received coupons, of whom 92 (51%) accepted the coupon, and 61 (66%) men redeemed the coupon. Those who redeemed test kits and completed a survey (n = 53) were more ethnically diverse (chi(2) = 100.69, p < .01) than those receiving the coupon. More than half had not tested in the past 6 months (50%) or never tested (7%). Importantly, men who had never tested or who last tested more than 6 months ago were among those most likely to take the free test kit. We found bathhouse distribution could reach a population of men who have sex with men most in need of improved access to HIV testing. Future studies should consider means of improved follow-up and linkage to care for those who test positive. PMID- 26883731 TI - Ultraviolet Stand-off Raman Measurements Using a Gated Spatial Heterodyne Raman Spectrometer. AB - A spatial heterodyne Raman spectrometer (SHRS) is evaluated for stand-off Raman measurements in ambient light conditions using both ultraviolet (UV) and visible pulsed lasers with a gated ICCD detector. The wide acceptance angle of the SHRS simplifies optical coupling of the spectrometer to the telescope and does not require precise laser focusing or positioning of the laser on the sample. If the laser beam wanders or loses focus on the sample, as long as it is in the field of view of the SHRS, the Raman signal will still be collected. The SHRS is not overly susceptible to vibrations, and a vibration isolated optical table was not necessary for these measurements. The system performance was assessed by measuring stand-off UV and visible Raman spectra of a wide variety of materials at distances up to 18 m, using 266 nm and 532 nm pulsed lasers, with 12.4 in. and 3.8 in. aperture telescopes, respectively. PMID- 26883732 TI - "Is there an emerging need for new antifungals?". PMID- 26883728 TI - Fc receptor-mediated phagocytosis in tissues as a potent mechanism for preventive and therapeutic HIV vaccine strategies. AB - Although the development of a fully protective HIV vaccine is the ultimate goal of HIV research, to date only one HIV vaccine trial, the RV144, has successfully induced a weakly protective response. The 31% protection from infection achieved in the RV144 trial was linked to the induction of nonneutralizing antibodies, able to mediate antibody-dependent cell-mediated cytotoxicity (ADCC), suggestive of an important role of Fc-mediated functions in protection. Similarly, Fc mediated antiviral activity was recently shown to play a critical role in actively suppressing the viral reservoir, but the Fc effector mechanisms within tissues that provide protection from or after infection are largely unknown. Here we aimed to define the landscape of effector cells and Fc receptors present within vulnerable tissues. We found negligible Fc receptor-expressing natural killer cells in the female reproductive and gastrointestinal mucosa. Conversely, Fc receptor-expressing macrophages were highly enriched in most tissues, but neutrophils mediated superior antibody-mediated phagocytosis. Modifications in Fc domain of VRC01 antibody increased phagocytic responses in both phagocytes. These data suggest that non-ADCC-mediated mechanisms, such as phagocytosis and neutrophil activation, are more likely to play a role in preventative vaccine or reservoir-eliminating therapeutic approaches. PMID- 26883733 TI - Pressure sensitive microparticle adhesion through biomimicry of the pollen-stigma interaction. AB - Many soft biomimetic synthetic adhesives, optimized to support macroscopic masses (~kg), have been inspired by geckos, insects and other animals. Far less work has investigated bioinspired adhesion that is tuned to micro- and nano-scale sizes and forces. However, such adhesive forces are extremely important in the adhesion of micro- and nanoparticles to surfaces, relevant to a wide range of industrial and biological systems. Pollens, whose adhesion is critical to plant reproduction, are an evolutionary-optimized system for biomimicry to engineer tunable adhesion between particles and micro-patterned soft matter surfaces. In addition, the adhesion of pollen particles is relevant to topics as varied as pollinator ecology, transport of allergens, and atmospheric phenomena. We report the first observation of structurally-derived pressure-sensitive adhesion of a microparticle by using the sunflower pollen and stigma surfaces as a model. This strong, pressure-sensitive adhesion results from interlocking between the pollen's conical spines and the stigma's receptive papillae. Inspired by this behavior, we fabricated synthetic polymeric patterned surfaces that mimic the stigma surface's receptivity to pollen. These soft mimics allow the magnitude of the pressure-sensitive response to be tuned by adjusting the size and spacing of surface features. These results provide an important new insight for soft material adhesion based on bio-inspired principles, namely that ornamented microparticles and micro-patterned surfaces can be designed with complementarity that enable a tunable, pressure-sensitive adhesion on the microparticle size and length scale. PMID- 26883734 TI - Functional hydroxyapatite bioceramics with excellent osteoconductivity and stern interface induced antibacterial ability. AB - The biocompatibility and antibacterial properties of hydroxyapatite (HAp) bioceramics are crucial in medical applications. However, it is still a challenge to control HAp with antibacterial ability while maintaining other biological properties in the development of bioactive bone implants. Herein, we report functional silver ion substituted HAp bioceramics with excellent osteoconductivity and efficient antibacterial activity and propose a stern interface induced antibacterial mechanism of such bioactive ceramics. In this antibacterial process, the concentration of Ag(+) at the stern-interface of Ag/HAp bioceramics is nearly 5 times higher than that in the bulk solution due to the trace dopant Ag(+) enrichment in the stern layer of the electric double layer at the negatively charged surface of Ag/HAp bioceramics. Trace Ag-doping in HAp induces a positive shift of zeta potential and increase of hydrophilicity, which may help inhibit bacterial proliferation. The positive osteoblast adhesion, proliferation and differentiation of ultra-trace doped Ag/HAp are also demonstrated through actin cytoskeleton staining, MTT and alkaline phosphatase (ALP) activity assays. This work may enlighten us on the artificial design of novel smart anti-infective bone grafts using ultra-trace functional elements and also suggest its potential applications in orthopedic surgery and bone osseointegration. PMID- 26883735 TI - Correction: Strain effects on oxygen migration in perovskites. AB - Correction for 'Strain effects on oxygen migration in perovskites' by Tam Mayeshiba et al., Phys. Chem. Chem. Phys., 2015, 17, 2715-2721. PMID- 26883737 TI - Associations between diabetes self-management and microvascular complications in patients with type 2 diabetes. AB - OBJECTIVES: Diabetes is a major public health problem that is approaching epidemic proportions globally. Diabetes self-management can reduce complications and mortality in type 2 diabetic patients. The purpose of this study was to examine associations between diabetes self-management and microvascular complications in patients with type 2 diabetes. METHODS: In this cross-sectional study, 562 Iranian patients older than 30 years of age with type 2 diabetes who received treatment at the Diabetes Research Center of the Endocrinology and Metabolism Research Institute of the Tehran University of Medical Sciences were identified. The participants were enrolled and completed questionnaires between January and April 2014. Patients' diabetes self-management was assessed as an independent variable by using the Diabetes Self-Management Questionnaire translated into Persian. The outcomes were the microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy), identified from the clinical records of each patient. A multiple logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between diabetes self-management and the microvascular complications of type 2 diabetes, adjusting for potential confounders. RESULTS: After adjusting for potential confounders, a significant association was found between the diabetes self-management sum scale and neuropathy (adjusted OR, 0.64; 95% CI, 0.45 to 0.92, p=0.01). Additionally, weak evidence was found of an association between the sum scale score of diabetes self-management and nephropathy (adjusted OR, 0.71; 95% CI, 0.47 to 1.05, p=0.09). CONCLUSIONS: Among patients with type 2 diabetes, a lower diabetes self management score was associated with higher rates of nephropathy and neuropathy. PMID- 26883739 TI - The interaction between morphine and propranolol in chemical and electrical seizure models of mice. AB - OBJECTIVES: Morphine and propranolol have different effects on seizure. Several studies have shown interaction between adrenergic and opioid systems in different models. In this study, interaction between morphine and propranolol in different seizure models was examined in mice. METHODS: In this study, three seizure models, including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ and electroshock, were examined in mice. Animals were injected with different doses of morphine or propranolol in the 60th and 45th min, before seizure induction, respectively. RESULTS: Acute administration of propranolol or lower doses of morphine induced an anticonvulsant effect in intravenous PTZ, intraperitoneal PTZ and electroshock-induced seizure models; on the contrary, higher doses of morphine exert proconvulsant effects in all three models. Also additive anticonvulsant effect of propranolol and lower doses of morphine was observed in all examined models. The additive anti-seizure effect of propranolol and lower doses of morphine was blocked by naltrexone in intraperitoneal PTZ model. Moreover, the anticonvulsant effect of propranolol was inhibited by naltrexone in intraperitoneal PTZ seizure model of mice. Propranolol restrained the proconvulsant effects in higher doses of morphine in clonic seizures of intravenous and intraperitoneal PTZ models. DISCUSSION: In conclusion, we believe that this is the first study that has indicated the interaction of propranolol and lower doses of morphine in the anticonvulsant effects in three seizure models of intravenous PTZ, intraperitoneal PTZ and electroshock. The involvement of MU opioid receptor in this interaction was also demonstrated. Simultaneously, we showed the interaction between propranolol and higher doses of morphine in proconvulsant effects. PMID- 26883738 TI - Application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract. AB - OBJECTIVES: Cataract is a prevalent disease in the elderly, and negatively influences patients' quality of life. This study was conducted to study the application of the World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) to patients with cataract. METHODS: In this cross-sectional study, 300 patients with cataract were studied in Neyshabur, Iran from July to October 2014. The Iranian version of the WHOQOL-BREF questionnaire was used to measure their quality of life. Cronbach's alpha coefficient, Pearson's correlation coefficient, the paired t-test, the independent t-test, and a linear regression model were used to analyze the data in SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). RESULTS: The mean age of the participants was 68.11+/-11.98 years, and most were female (53%). The overall observed Cronbach's alpha coefficient for the WHOQOL-BREF was 0.889, ranging from 0.714 to 0.810 in its four domains. The total mean score of the respondents on the WHOQOL-BREF was 13.19. The highest and lowest mean scores were observed in the social relationship domain (14.11) and the physical health domain (12.29), respectively. A backward multiple linear regression model found that duration of disease and marital status were associated with total WHOQOL scores, while age, duration of disease, marital status, and income level were associated with domains one through four, respectively (p<0.05). CONCLUSIONS: The reliability analysis conducted in this study indicated that the WHOQOL-BREF scale exhibited an acceptable degree of internal consistency in the measurement of the quality of life of patients with cataract. It was also found that the patients with cataract who were surveyed reported a relatively moderate quality of life. PMID- 26883740 TI - Regression of moyamoya-associated weak spots on the distal anterior choroidal artery following surgical revascularization. AB - A 20-year-old female with moyamoya disease presented with acute intraventricular hemorrhage. Cerebral angiography demonstrated that the anterior choroidal artery (AChA) was responsible for the bleeding, but the precise point of rupture was unpredictable, because multiple angiographic weak spots were found on the artery. As direct targeting of the rupture point was unfeasible, we performed encephalo duro-arterio-synangiosis to decrease the hemodynamic overload on the AChA. This revascularization procedure alone successfully induced the regression of all weak points. In this report, we demonstrated that, when direct targeting of weak points was not feasible, a revascularization procedure was an acceptable alternative. PMID- 26883741 TI - Tibial component rotation in total knee arthroplasty. AB - BACKGROUND: Both the range of motion (ROM) technique and the tibial tubercle landmark (TTL) technique are frequently used to align the tibial component into proper rotational position during total knee arthroplasty (TKA). The aim of the study was to assess the intra-operative differences in tibial rotation position during computer-navigated primary TKA using either the TTL or ROM techniques. The ROM technique was hypothesized to be a repeatable method and to produce different tibial rotation positions compared to the TTL technique. METHODS: A prospective, observational study was performed to evaluate the antero-posterior axis of the cut proximal tibia using both the ROM and the TTL technique during primary TKA without postoperative clinical assessment. Computer navigation was used to measure this difference in 20 consecutive knees of 20 patients who underwent a posterior stabilized total knee arthroplasty with a fixed-bearing polyethylene insert and a patella resurfacing. RESULTS: The ROM technique is a repeatable method with an interclass correlation coefficient (ICC2) of 0.84 (p < 0.001). The trial tibial baseplate was on average 4.56 degrees externally rotated compared to the tubercle landmark. This difference was statistically significant (p = 0.028). The amount of maximum intra-operative flexion and the pre-operative mechanical axis were positively correlated with the magnitude of difference between the two methods. CONCLUSIONS: It is important for the orthopaedic surgeon to realise that there is a significant difference between the TTL technique and ROM technique when positioning the tibial component in a rotational position. This difference is correlated with high maximum flexion and mechanical axis deviations. PMID- 26883742 TI - Trends in equity in use of maternal health services in urban and rural Bangladesh. AB - BACKGROUND: Maternal healthcare utilization is a major determinant of maternal mortality. Bangladesh is experiencing a rapid pace of urbanization with all future growth in population expected to be in urban areas. Health care infrastructure is different in urban and rural areas thus warranting an examination of equity in use rates of maternal healthcare. This paper addresses whether the urban-rural and rich-poor gaps in use of selected maternal healthcare indicators have narrowed or widened over the last decade. The paper also explores changes in the service provider environment in urban and rural domains. METHODS: The 2001 and 2010 Bangladesh Maternal Mortality and Health Care Survey data were used to examine trends in use of antenatal care from medically trained providers and in deliveries taking place at health facilities. Separate wealth quintiles were constructed for urban and rural areas. The concentration index was calculated for urban and rural areas to measure equity in distribution of antenatal care (ANC) and facility deliveries across wealth quintiles in urban and rural domains. RESULTS: The gap in use of ANC provided by medically trained personnel narrowed in urban and rural areas between 2001 and 2010 while that in facility deliveries widened. The difference in use of ANC by the rich and the poor was not as pronounced as that in utilization of facilities for deliveries. Over the last decade, equity in utilization of health facilities for deliveries has improved at a faster rate in urban areas. Private sector has surpassed the public sector and appears to be the dominant provider of maternal healthcare in both domains with the share of NGOs increasing in urban areas. CONCLUSIONS: The faster pace of improvement in equity in maternal healthcare utilization in urban areas is reflective of the changing service environment in urban and rural areas, among other factors. PMID- 26883743 TI - Graphene-based large area dye-sensitized solar cell modules. AB - We demonstrate spray coating of graphene ink as a viable method for large-area fabrication of graphene-based dye-sensitized solar cell (DSSC) modules. A graphene-based ink produced by liquid phase exfoliation of graphite is spray coated onto a transparent conductive oxide substrate to realize a large area (>90 cm(2)) semi-transparent (transmittance 44%) counter-electrode (CE) replacing platinum, the standard CE material. The graphene-based CE is successfully integrated in a large-area (43.2 cm(2) active area) DSSC module achieving a power conversion efficiency of 3.5%. The approach demonstrated here paves the way to all-printed, flexible, and transparent graphene-based large-area and cost effective photovoltaic devices on arbitrary substrates. PMID- 26883744 TI - A cross-sectional study on schistosomiasis and soil-transmitted helminths in Mbita district, western Kenya using different copromicroscopic techniques. AB - BACKGROUND: Identification of populations to be targeted for individual treatment and broad-spectrum therapy in schistosomiasis-endemic areas, assessment of therapy efficacy, morbidity, and evaluation of control strategies need to be based on reliable diagnostic tools. Kato-Katz is routinely used and remains the standard diagnostic technique for schistosomiasis, despite its many challenges. This study was conducted in Nyamanga village, Mbita, western Kenya, and evaluated the diagnostic performance of Kato-Katz, Mini-Parasep and modified Mini-FLOTAC techniques in detection of Schistosoma mansoni and soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and hookworm) ova. METHODS: Stool samples from 132 individuals were screened for eggs of S. mansoni by the 3 techniques. Mini-Parasep faecal parasite concentrator (Apacor Ltd, England), a single-use diagnostic device with a built-in filter for faecal concentration of helminth eggs by sedimentation was employed on stool samples fixed in 10% formalin. A modified Mini-FLOTAC (University of Naples, Italy) was based on floatation of helminths eggs with two different solutions (FS2 and FS7) using a closed system (Fill-FLOTAC) with 5% formalin. Kato-Katz was performed following WHO recommendation. Prevalence of S. mansoni and STH, sensitivity and degree of agreement among the 3 techniques were determined. RESULTS: Prevalence of S. mansoni was 47.0%, 34.1% and 20.5% by Mini-Parasep, Kato-Katz and modified Mini FLOTAC FS7 techniques, respectively. Prevalence of any STH infection was 6.1%, 3.0%, 6.1% and 6.8% by Mini-Parasep, Kato-Katz, modified Mini-FLOTAC FS2 and modified Mini-FLOTAC FS7 techniques, respectively. Considering the pooled results of the three methods (Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7) as diagnostic 'gold' standard, the sensitivity of Mini-Parasep, Kato-Katz and modified Mini-FLOTAC FS7 for S. mansoni was 77.5%, 56.1%, and 33.8%, respectively. Mini-Parasep and modified Mini-FLOTAC FS7 techniques had moderate (kappa = 0.46) and fairly good (kappa = 0.25) agreements with Kato-Katz for S. mansoni, respectively. Mini-Parasep detected a higher proportion of light intensity S. mansoni infections compared to Kato-Katz, which detected high proportions of heavy infections. Mini-Parasep detected a similar mean number of S. mansoni eggs per gram (EPG) of stool compared to the standard Kato-Katz (62.9 vs 97.3; t (131) = -0.49, P = 0.6265) and significantly higher EPG compared to the modified Mini-FLOTAC FS7 (62.9 vs 34.6; t (131) = 5.39, P < 0.0001). CONCLUSIONS: The high sensitivity of Mini-Parasep suggests its promising potential as an alternative tool in enhancing diagnosis and in monitoring schistosomiasis transmission and determining endpoint of intervention programs, especially in low endemicity areas. Mini-Parasep is also easy to operate, safe and also permits work with fresh stool. PMID- 26883747 TI - How to improve communication quality with patients and relatives in the ICU. AB - The experience of intensive care for patients and their families is known to be very stressful and may result in both acute and chronic psychological problems that include sleep disturbance, depression, anxiety and post-traumatic stress disorder. While some non-modifiable risk factors for psychological harm are known, there are also a several modifiable risk factors that may be addressed using strategically planned interventions such as optimal communication techniques. Effective communication is increasingly being recognized as an essential non-technical skills for all intensive care clinicians. One situation which is central to communication in the ICU is the family meeting. Similar to other procedures in the ICU, training, practice, preparation and reflective review may improve performance when conducting family meetings and lead to better outcomes for patients and families. PMID- 26883746 TI - Lymph node micrometastases are associated with disease recurrence and poor survival for early-stage non-small cell lung cancer patients: a meta-analysis. AB - BACKGROUND: We performed a meta-analysis to clarify whether the molecular detection of tumor cells or micrometastases in the lymph node (LN) indicates a high risk of disease recurrence and poor survival in negative pathologic lymph node status non-small cell lung cancer (NSCLC). METHODS: A literature search was performed using relevant keywords. We searched relevant studies from PubMed, Embase, and the Cochrane Library. Direct and indirect meta-estimates were generated using Review Manager software with fixed effects for the study. Study to-study heterogeneity was summarized using I (2) statistics and predictive intervals (PIs). RESULTS: Our analysis of eight eligible studies revealed that patients with lymph node micrometastases (LNMM) were associated with poor overall survival (OS) (HR, 1.98; 95 % CI, 1.50 to 2.62; p < 0.00001) and disease-free survival (DFS) (HR, 2.34; 95 % CI, 1.67-3.27; p < 0.00001). CONCLUSION: LNMM is associated with an increased risk of disease recurrence and poor survival in patients with negative pathologic node negative NSCLC. Thus, these patients need to be carefully followed up after the initial pulmonary resection. PMID- 26883745 TI - Functional imaging of hepatocellular carcinoma using diffusion-weighted MRI and (18)F-FDG PET/CT in patients on waiting-list for liver transplantation. AB - BACKGROUND: To compare the apparent diffusion coefficient (ADC) on diffusion weighted imaging (DWI) with the standardized uptake values (SUV) measured by(18)F FDG-PET/CT in naive hepatocellular carcinoma (HCC) nodules, and to determine whether these markers are associated with tumours at high-risk of aggressiveness. METHODS: From 2007 to 2010, all patients with HCC on the waiting list for liver transplantation and who underwent both FDG-PET/CT and 1.5-T DWI-MRI (b values: 0, 200, 400, and 800 s/mm(2)) were included in this institutional review board approved retrospective study. Tumour size, tumour ADC, tumour-to-liver ADC ratio (ADCT/L), maximal tumour SUV and tumour-to-liver SUV ratio (SUVT/L) were measured and compared to serum alpha-fetoprotein (AFP) levels, tumour size and differentiation grade on explanted specimens. RESULTS: A total of 37 HCC nodules in 28 patients were available for correlation between MRI and PET/CT, 7 of which (in 7 patients) showed a SUVT/L > 1.15. We did not find any correlation between tumour ADC or ADCT/L and tumour SUV or SUVT/L. To note, SUVT/L was positively correlated with AFP levels (R = 0.95, P <= 0.0001), while ADCT/L was not (P = 0.73). Twenty-four patients (with 32 nodules) underwent liver transplantation. In this subgroup, an increased SUVT/L ratio was associated with larger tumours (average size, 32 +/- 14 mm; range, 18-60 mm; P < 0.0001) and with poor differentiation on pathology (grades 3 and 4; P = 0.04), while ADCT/L was neither associated with tumour size or differentiation grade. CONCLUSIONS: ADC and SUV measures in HCC nodules are not correlated. SUVT/L ratio correlates with AFP levels, tumour size and poor differentiation, and should probably be integrated as a co-variable in a predictive outcome model of patients on the waiting-list for liver transplantation. PMID- 26883748 TI - Patient-controlled analgesia: past, present and future. PMID- 26883749 TI - A zwitterionic 1D/2D polymer co-crystal and its polymorphic sub-components: a highly selective sensing platform for HIV ds-DNA sequences. AB - Polymorphic compounds {[Cu(dcbb)2(H2O)2].10H2O}n (2, 1D chain), [Cu(dcbb)2]n (3, 2D layer) and their co-crystal {[Cu(dcbb)2(H2O)][Cu(dcbb)2]2}n (4) have been prepared from the coordination reaction of a 2D polymer [Na(dcbb)(H2O)]n (1, H2dcbbBr = 1-(3,5-dicarboxybenzyl)-4,4'-bipyridinium bromide) with Cu(NO3)2.3H2O at different temperatures in water. Compounds 2-4 have an identical metal-to ligand stoichiometric ratio of 1 : 2, but absolutely differ in structure. Compound 3 features a 2D layer structure with aromatic rings, positively charged pyridinium and free carboxylates on its surface, promoting electrostatic, pi stacking and/or hydrogen-bonding interactions with the carboxyfluorescein (FAM) labeled probe single-stranded DNA (probe ss-DNA, delineates as P-DNA). The resultant P-DNA@3 system facilitated fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@3 system functions as an efficient fluorescent sensor selective for HIV double-stranded DNA (HIV ds-DNA) due to the formation of a rigid triplex structure with the recovery of FAM fluorescence. The system reported herein also distinguishes complementary HIV ds DNA from mismatched target DNA sequences with the detection limit of 1.42 nM. PMID- 26883750 TI - "It Looks Like an Adult Sweetie Shop": Point-of-Sale Tobacco Display Exposure and Brand Awareness in Scottish Secondary School Students. AB - INTRODUCTION: As further restrictions have been placed on tobacco advertising and promotions, point-of-sale (PoS) displays of cigarettes in shops have become an increasingly important source of young people's exposure to tobacco products. This study explored the relationship between PoS displays of cigarettes and brand awareness among secondary school students in Scotland. METHODS: Cross-sectional school surveys (n = 1406) and focus groups (n = 86) were conducted with S2 (13-14 years) and S4 (15-16 years) students in four schools of differing socioeconomic status in 2013, prior to the PoS display ban in large shops. Adjusted negative binomial regression analysis examined associations between brand awareness and exposure variables (visiting tobacco retailers, noticing displays of tobacco products). RESULTS: Students visiting small shops more frequently (relative rate ratio [RRR] 1.19, 95% confidence interval [CI] 1.01-1.41) and those who noticed cigarette displays in small shops (RRR 1.24, 95% CI 1.03-1.51) and large supermarkets (RRR 1.15, 95% CI 1.01-1.30) had higher brand awareness. The focus groups supported these findings. Participants described PoS tobacco displays as being eye-catching, colorful and potentially attractive to young people. CONCLUSIONS: This mixed-methods study showed that higher cigarette brand awareness was significantly associated with regularly visiting small shops and noticing PoS displays in small and large shops, even when students' smoking status, smoking in their social networks, leisure activities, and demographics were included as confounding variables. This highlights the importance of PoS displays of tobacco products in increasing brand awareness, which is known to increase youth smoking susceptibility, and thus the importance of implementing PoS display bans in all shops. IMPLICATIONS: As increasing restrictions have been placed on tobacco promotion in many countries, PoS displays of cigarettes in shops have become an important source of young people's exposure to tobacco products and marketing. This mixed-methods study showed that prior to the PoS display ban in Scotland, and controlling for other factors, 13- and 15-year olds who regularly visited small shops and those who noticed PoS displays in small and large shops, had a higher awareness of cigarette brands. This highlights the importance of PoS displays in increasing youth brand awareness, which increases smoking susceptibility, and thus the need for comprehensive bans on PoS displays which cover all shops. PMID- 26883752 TI - Erratum to: Rice GDP-mannose pyrophosphorylase OsVTC1-1 and OsVTC1-3 play different roles in ascorbic acid synthesis. PMID- 26883751 TI - The combination of blue dye and radioisotope versus radioisotope alone during sentinel lymph node biopsy for breast cancer: a systematic review. AB - BACKGROUND: The combination of blue dye and radioisotope is most widely used to identify sentinel lymph nodes (SLNs) in patients with breast cancer. However, some individual studies suggested that dual tracers did not have an advantage over radioisotope alone in detecting SLNs. We performed a systematic review to investigate the added value of blue dye in addition to radioisotope. METHODS: We searched Pubmed and Embase. Prospective studies that compared the combination of radioisotope and blue dye with radioisotope alone were selected. The identification rate of SLNs and the false-negative rate were the main outcomes of interest. The odds ratios (ORs) and 95% confidential intervals (CIs) were calculated by using random-effects model. RESULTS: Twenty-four studies were included. The combination of radioisotope and blue dye showed higher identification rate than radioisotope alone (OR = 2.03, 95% CI 1.53-2.69, P < 0.05). However, no statistically significant difference was revealed for patients after neoadjuvant chemotherapy (OR = 1.64, 95% CI 0.82-3.27, P > 0.05), or for studies with high proportion of patients with positive lymphoscintigraphy (OR = 1.41, 95% CI 0.83-2.39, P > 0.05). Dual tracers did not significantly lower the false-negative rate compared with radioisotope alone (OR = 0.76, 95% CI 0.44 1.29, P > 0.05). CONCLUSIONS: Although the combination of blue dye and radioisotope outperformed radioisotope alone in SLN detection, the superiority for dual tracers may be limited for patients with positive lymphoscintigraphy or for those after neoadjuvant chemotherapy. Besides, the combined modality did not help lower the false-negative rate. PMID- 26883753 TI - Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device. AB - Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies. PMID- 26883754 TI - Propylene glycol-embodying deformable liposomes as a novel drug delivery carrier for vaginal fibrauretine delivery applications. AB - The purpose of this work was to develop and characterize the fibrauretine (FN) loaded propylene glycol-embodying deformable liposomes (FDL), and evaluate the pharmacokinetic behavior and safety of FDL for vaginal drug delivery applications. FDL was characterized for structure, particle size, zeta potential, deformability and encapsulation efficiency; the ability of FDL to deliver FN across vagina tissue in vitro and the distribution behavior of FN in rat by vaginal drug delivery were investigated, the safety of FDL to the vagina of rabbits and rats as well as human vaginal epithelial cells (VK2/E6E7) were also evaluated. Results revealed that: (i) the FDL have a closed spherical shape and lamellar structure with a homogeneous size of 185+/-19nm, and exhibited a negative charge of -53+/-2.7mV, FDL also have a good flexibility with a deformability of 92+/-5.6 (%phospholipids/min); (ii) the dissolving capacity of inner water phase and hydrophilicity of phospholipid bilayers of deformable liposomes were increased by the presence of propylene glycol, this may be elucidated by the fluorescent probes both lipophilic Nile red and hydrophilic calcein that were filled up the entire volume of the FDL uniformly, so the FDL with a high entrapment capacity (were calculated as percentages of total drug) for FN was 78+/-2.14%; (iii) the permeability of FN through vaginal mucosa was obviously improved by propylene glycol-embodying deformable liposomes, no matter whether the FN loaded in liposomes or not, although FN loaded in liposomes caused the highest permeability and drug reservoir in vagina; (iv) the FN mainly aggregated in the vagina and uterus, then the blood, spleen, liver, kidney, heart and lungs for vaginal drug delivery, this indicating vaginal delivery of FDL have a better 'vaginal local targeting effect'; and (v) the results of safety evaluation illustrate that the FDL is non-irritant and well tolerated in vivo, thereby establishing its vaginal drug delivery potential. These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine. PMID- 26883756 TI - Long-Term Fluctuations in Traumatic Symptoms of High School Girls Who Survived from the 2011 Japan Tsunami: Series of Questionnaire-Based Cross-Sectional Surveys. AB - On March 11, 2011, Japan was struck by a massive earthquake and tsunami. The tsunami caused tremendous damage and traumatized children. We aimed to evaluate and compare the changes in the traumatic symptoms of high school girls 8, 20, 30, and 42 months after the 2011 tsunami. The Post-Traumatic Stress Symptoms for Children 15 items (PTSSC-15), a self-rating questionnaire on traumatic symptoms, was administered to 811 high school girls at the above-mentioned intervals. We calculated the total score, post-traumatic stress disorder (PTSD) subscale, and depression subscale of PTSSC-15. The total score was correlated with house damage, evacuation experience, and bereavement experience. The PTSSC-15 total scores of high school girls with traumatic experience were significantly higher than the scores of children without these experiences (all p < 0.0001). The PTSSC 15 total score did not decrease significantly over time. Furthermore, the PTSD subscale of the PTSSC-15 did not significantly improved over the study duration. However, the depression subscale of the PTSSC-15 significantly improved at 30 months, but significantly worsened at 42 months (both p < 0.0001). This study demonstrates that the traumatic symptoms of high school girls who survived the massive tsunami fluctuated unpredictably with time. Nonetheless, high school girls continued to suffer depressive symptoms (insomnia, withdrawal, appetite loss, inattention, and physical symptoms) after 42 months. PMID- 26883757 TI - Investigation of the Reuse of Immobilized Lipases in Biodiesel Synthesis: Influence of Different Solvents in Lipase Activity. AB - Biodiesel production catalyzed by immobilized lipases offers the possibility of easy reuse of the catalyst, which is very important to minimize costs and to make this process economically feasible. In this study, the reuse of three commercial immobilized lipases (Novozym 435, Lipozyme RM IM, and Lipozyme TL IM) was investigated in ethanolysis of soybean oil. The effect of the use of solvents (ethanol, butanol, and hexane) to wash the immobilized lipases before the enzyme reuse was evaluated, as well as the lipase reuse without solvent washing. The washing with butanol and ethanol led to the lowest decrease in ester yield after the first batch and allowed the highest glycerol removal (>85 %) from biocatalysts. The biocatalysts were incubated at 50 degrees C for 2 h in these three solvents. Esterification activities of the enzyme preparations, scanning electron microscopy (SEM) analyses of the beads, and protein content in organic phase were evaluated before and after incubation in the solvent. SEM analysis showed a significant change in beads morphology of Novozym 435 after contact with hexane. For Lipozyme TL IM lipase, this effect was visualized with ethanol. PMID- 26883755 TI - Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure. AB - A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure. PMID- 26883758 TI - Disrupted brain connectivity networks in acute ischemic stroke patients. AB - Neuroimaging studies have shown that local brain lesions could result in abnormal information transfer far from the lesion site in acute ischemic stroke (AIS) patients; yet, little is known about alternations of the topological organization of whole-brain networks in AIS. By using resting state functional magnetic resonance imaging (MRI) and graph theory analysis, we systematically investigated the topological properties of the functional brain networks of 28 healthy controls (HC, age: 56.9 +/- 0.45 years) and 29 AIS (age: 57.6 +/- 0.21 years) with proximal anterior circulation occlusion within 12 h of symptom onset. In our results, both the AIS and HC groups exhibited small-world network organization, suggesting a functional balance between local specialization and global integration. However, compared with the HC, the AIS patients had a lower shortest path length and higher global efficiency, indicating a tendency of randomization in patients' functional brain networks. The AIS patients had an increased nodal degree in the precuneus (PCUN), middle frontal gyrus (MFG), medial part of the superior frontal gyrus (SFGmed), orbital part of the middle frontal gyrus, and the opercular part of the inferior frontal gyrus, and increased nodal efficiency in the PUCN, MFG, SFGmed, and the angular gyrus. The decreased nodal degree in AIS was found in the heschl gyrus (HES), and no significant decreased nodal efficiency was observed. The dysfunctional connections were mainly concentrated in the HES and prefrontal cortex. Furthermore, the altered nodal centrality of the MFG and abnormal functional connectivity in AIS were associated with patients' Mini-Mental State Examination scores. These results suggested that interrupted functional connectivity in language system organization after focal brain lesions could also result in disruptions in the topological organization of other brain circuits, and this may contribute to disturbances in cognition in AIS patients. PMID- 26883759 TI - Small-molecule inhibitors of FGFR, integrins and FAK selectively decrease L1CAM stimulated glioblastoma cell motility and proliferation. AB - PURPOSE: The cell adhesion/recognition protein L1CAM (L1; CD171) has previously been shown to act through integrin, focal adhesion kinase (FAK) and fibroblast growth factor receptor (FGFR) signaling pathways to increase the motility and proliferation of glioblastoma cells in an autocrine/paracrine manner. Here, we investigated the effects of clinically relevant small-molecule inhibitors of the integrin, FAK and FGFR signaling pathways on glioblastoma-derived cells to determine their effectiveness and selectivity for diminishing L1-mediated stimulation. METHODS: The effects of the FGFR inhibitor PD173074, the FAK inhibitors PF431396 and Y15 and the alphavbeta3/alphavbeta5 integrin inhibitor cilengitide were assessed in L1-positive and L1-negative variants of the human glioblastoma-derived cell lines T98G and U-118 MG. Their motility and proliferation were quantified using time-lapse microscopy and DNA content/cell cycle analyses, respectively. RESULTS: The application of all four inhibitors resulted in reductions in L1-mediated motility and proliferation rates of L1 positive glioblastoma-derived cells, down to the level of L1-negative cells when used at nanomolar concentrations, whereas no or much smaller reductions in these rates were obtained in L1-negative cells. In addition, we found that single inhibitor treatment resulted in maximum effects (i.e., combinations of FAK or integrin inhibitors with the FGFR inhibitor were rarely more effective). These results suggest that FAK may act as a point of convergence between the integrin and FGFR signaling pathways stimulated by L1 in these cells. CONCLUSIONS: We here show for the first time that small-molecule inhibitors of FGFR, integrins and FAK effectively and selectively abolish L1-stimulated migration and proliferation of glioblastoma-derived cells. Our results suggest that these inhibitors have the potential to reduce the aggressiveness of high-grade gliomas expressing L1. PMID- 26883760 TI - Optimization of the process variables of tilianin-loaded composite phospholipid liposomes based on response surface-central composite design and pharmacokinetic study. AB - Tilianin is attracting considerable attention because of its antihypertensive, anti-atherogenic and anticonvulsive efficacy. However, tilianin has poor oral bioavailability. Thus, to improve the oral bioavailability of tilianin, composite phospholipid liposomes were adopted in this work as a novel nanoformulation. The aim was to develop and formulate tilianin composite phospholipid liposomes (TCPLs) through ethanol injection and to apply the response surface-central composite design to optimize the tilianin composite phospholipid liposome formulation. The independent variables were the amount of phospholipids (X1), amount of cholesterol (X2) and weight ratio of phospholipid to drug (X3); the depended variables were particle size (Y1) and encapsulation efficiency (EE) (Y2) of TCPLs. Results indicated that the optimum preparation conditions were as follows: phospholipid amount, 500 mg, cholesterol amount, 50mg and phospholipid/drug ratio, 25. These variables were also the major contributing variables for particle size (101.4 +/- 6.1 nm), higher EE (90.28% +/- 1.36%), zeta potential (-18.3 +/- 2.6 mV) and PDI (0.122 +/- 0.027). Subsequently, differential scanning calorimetry techniques were used to investigate the molecular interaction in TCPLs, and the in vitro drug release of tilianin and TCPLs was investigated by the second method of dissolution in the Chinese Pharmacopoeia (Edition 2015). Furthermore, pharmacokinetics in Sprague Dawley rats was evaluated using a rat jugular vein intubation tube. Results demonstrated that the Cmax of TCPLs became 5.7 times higher than that of tilianin solution and that the area under the curve of TCPLs became about 4.6-fold higher than that of tilianin solution. Overall, our results suggested that the prepared tilianin composite phospholipid liposome formulations could be used to improve the bioavailability of tilianin after oral administration. PMID- 26883761 TI - Enhanced in vitro angiogenic behaviour of human umbilical vein endothelial cells on thermally oxidized TiO2 nanofibrous surfaces. AB - One of the major challenges in bone grafting is the lack of sufficient bone vascularization. A rapid and stable bone vascularization at an early stage of implantation is essential for optimal functioning of the bone graft. To address this, the ability of in situ TiO2 nanofibrous surfaces fabricated via thermal oxidation method to enhance the angiogenic potential of human umbilical vein endothelial cells (HUVECs) was investigated. The cellular responses of HUVECs on TiO2 nanofibrous surfaces were studied through cell adhesion, cell proliferation, capillary-like tube formation, growth factors secretion (VEGF and BFGF), and angiogenic-endogenic-associated gene (VEGF, VEGFR2, BFGF, PGF, HGF, Ang-1, VWF, PECAM-1 and ENOS) expression analysis after 2 weeks of cell seeding. Our results show that TiO2 nanofibrous surfaces significantly enhanced adhesion, proliferation, formation of capillary-like tube networks and growth factors secretion of HUVECs, as well as leading to higher expression level of all angiogenic-endogenic-associated genes, in comparison to unmodified control surfaces. These beneficial effects suggest the potential use of such surface nanostructures to be utilized as an advantageous interface for bone grafts as they can promote angiogenesis, which improves bone vascularization. PMID- 26883763 TI - Late-onset panhypopituitarism in a 72-year-old male patient treated with ipilimumab for metastatic melanoma: a case report. PMID- 26883762 TI - The CodY regulator is essential for virulence in Streptococcus suis serotype 2. AB - The main role of CodY, a global regulatory protein in most low G + C gram positive bacteria, is in transcriptional repression. To study the functions of CodY in Streptococcus suis serotype 2 (S. suis 2), a mutant codY clone named ?codY was constructed to explore the phenotypic variation between ?codY and the wild-type strain. The result showed that the codY mutation significantly inhibited cell growth, adherence and invasion ability of S. suis 2 to HEp-2 cells. The codY mutation led to decreased binding of the pathogen to the host cells, easier clearance by RAW264.7 macrophages and decreased growth ability in fresh blood of Cavia porcellus. The codY mutation also attenuated the virulence of S. suis 2 in BALB/c mice. Morphological analysis revealed that the codY mutation decreased the thickness of the capsule of S. suis 2 and changed the surface structures analylized by SDS-PAGE. Finally, the codY mutation altered the expressions of many virulence related genes, including sialic acid synthesis genes, leading to a decreased sialic acid content in capsule. Overall, mutation of codY modulated bacterial virulence by affecting the growth and colonization of S. suis 2, and at least via regulating sialic acid synthesis and capsule thickness. PMID- 26883765 TI - David Oliver: Senior nurses should stand up for nursing. PMID- 26883766 TI - Erratum: Inhibition of stationary phase respiration impairs persister formation in E. coli. PMID- 26883764 TI - Neuropsychological Test Performance in Cognitively Normal Spanish-speaking Nonagenarians with Little Education. AB - To find associations of age, sex, and education with neuropsychological test performance in cognitively normal Spanish-speaking Costa Rican nonagenarians with little education; to provide norms; and to compare their performance with similar Puerto Ricans. For 95 Costa Ricans (90-102 years old, 0-6 years of education), multiple regression assessed associations with demographics of performance on six neuropsychological tests. Analyses of covariance compared them with 23 Puerto Ricans (90-99 years old). Younger age and being female-but not education-were associated with better performance on some neuropsychological tests, in particular episodic memory. The Puerto Ricans performed better on learning and memory tasks. In cognitively intact Spanish-speaking nonagenarians with little or no education, education did not affect test performance. Additional studies of the effect of education on cognitive performance are warranted in other samples with extremely low education or old age. National differences in performance highlight the importance of group-specific norms. PMID- 26883767 TI - The Protective Effect of Transplanting Liver Cells Into the Mesentery on the Rescue of Acute Liver Failure After Massive Hepatectomy. AB - Postoperative liver failure is one of the most critical complications following extensive hepatectomy. Although transplantation of allogeneic hepatocytes is an attractive therapy for posthepatectomy liver failure, transplanting cells via the portal veins typically causes portal vein embolization. The embolization by transplanted cells would be lethal in patients who have undergone massive hepatectomy. Thus, transplant surgeons need to select extrahepatic sites as transplant sites to prevent portal vein embolization. We aimed to investigate the mechanism of how liver cells transplanted into the mesentery protect recipient rats from acute liver failure after massive hepatectomy. We induced posthepatectomy liver failure by 90% hepatectomy in rats. Liver cells harvested from rat livers were transplanted into the mesenteries of hepatectomized rats. Twenty percent of the harvested cells, which consisted of hepatocytes and nonparenchymal cells, were transplanted into each recipient. The survival rate improved significantly in the liver cell transplantation group compared to the control group 7 days after hepatectomy (69 vs. 7%). Histological findings of the transplantation site, in vivo imaging system study findings, quantitative polymerase chain reaction assays of the transplanted cells, and serum albumin measurements of transplanted Nagase analbuminemic rats showed rapid deterioration of viable transplanted cells. Although viable transplanted cells deteriorated in the transplanted site, histological findings and an adenosine-5'-triphosphate (ATP) assay showed that the transplanted cells had a protective effect on the remaining livers. These results indicated that the paracrine effects of transplanted liver cells had therapeutic effects. The same protective effects were observed in the hepatocyte transplantation group, but not in the liver nonparenchymal cell transplantation group. Therefore, this effect on the remnant liver was mainly due to the hepatocytes among the transplanted liver cells. We demonstrated that transplanted liver cells protect the remnant liver from severe damage after massive hepatectomy. PMID- 26883768 TI - Repeatability of infrared ocular thermography in assessing healthy and dry eyes. AB - PURPOSE: To investigate the inter-image, inter-occasion and inter-examiner repeatability of NEC infrared thermo-tracer TH 9260 in assessing healthy and dry eyes. METHODS: Ocular surface temperature (OST) was recorded using NEC infrared thermo-tracer TH 9260 on 21 healthy and 15 dry eyes. Data from the right eyes were analyzed. Marking of the ocular surface and OST acquisition was performed using a new 'diamond' demarcation method. Twelve OST indices were obtained at three different time points following a blink: 0s, 5s and 10s. Inter-image, inter occasion and inter-examiner repeatability of the infrared ocular thermography was evaluated by calculating coefficients of repeatability (COR). RESULTS: Ten out of the twelve tested OST indices had good repeatability with small inter-image variability (%COR: 0.2-0.9), inter-occasion variability (%COR: 2.1-3.7) and inter examiner variability (%COR: 1.5-3.7) for the three studied time points. Two of the OST indices (temperature standard deviation of the region of interest and radial temperature difference) had poor repeatability with much larger inter image variability (%COR: 8.9-140.7), inter-occasion variability (%COR: 47.5 153.5) and inter-examiner variability (%COR: 54.7-142.0) for the three studied time points. CONCLUSIONS: Most of the metrics adopted in this assessment can be considered to be highly repeatable. PMID- 26883769 TI - Wise therapeutic decisions for older patients. PMID- 26883770 TI - [Obesity: stigmatization, discrimination, body image]. AB - Obesity is a heterogeneous condition with multifactorial genesis (genetic predisposition, life-style, psychosocial situation), but there is a relatively homogeneous negative stereotype of obese individuals, because overweight and obesity are seen as self-inflicted disorders caused by physical inactivity and disorderd eating behavior. Obese individuals are confronted with far-reaching stigmatization and discrimination. Typical stereotypes are laziness, unattractiveness, work refusal. This negative image by the environment contributes to negative self-awareness and self-stigmatization, accompanied by a poor self-esteem and feelings of poor self-control and reduced self-efficacy, resulting in poor constructive coping strategies for overweight reduction. In addition, a disturbed body image combined with deep dissatisfaction with their own body is often found in many obese individuals. There is not always a close connection between body weight and body dissatisfaction. Young women and individuals with a binge eating disorder often show an increased body dissatisfaction as well. PMID- 26883771 TI - [Overtreatment: Initiatives to identify ineffective and inappropriate medical interventions]. AB - A growing number of international initiatives rise to the challenge of reduction of medical overuse. Increasingly, these activities are promoted by physicians and clinicians, and aim to identify and avoid inappropriate health interventions. This article places the Choosing Wisely initiative within the context of less well-known activities, 13 all together, and briefly describes their characteristics; in addition, similarities and differences regarding their methods are elaborated. PMID- 26883772 TI - Evaluating and comparing biomarkers with respect to the area under the receiver operating characteristics curve in two-phase case-control studies. AB - Two-phase sampling design, where biomarkers are subsampled from a phase-one cohort sample representative of the target population, has become the gold standard in biomarker evaluation. Many two-phase case-control studies involve biased sampling of cases and/or controls in the second phase. For example, controls are often frequency-matched to cases with respect to other covariates. Ignoring biased sampling of cases and/or controls can lead to biased inference regarding biomarkers' classification accuracy. Considering the problems of estimating and comparing the area under the receiver operating characteristics curve (AUC) for a binary disease outcome, the impact of biased sampling of cases and/or controls on inference and the strategy to efficiently account for the sampling scheme have not been well studied. In this project, we investigate the inverse-probability-weighted method to adjust for biased sampling in estimating and comparing AUC. Asymptotic properties of the estimator and its inference procedure are developed for both Bernoulli sampling and finite-population stratified sampling. In simulation studies, the weighted estimators provide valid inference for estimation and hypothesis testing, while the standard empirical estimators can generate invalid inference. We demonstrate the use of the analytical variance formula for optimizing sampling schemes in biomarker study design and the application of the proposed AUC estimators to examples in HIV vaccine research and prostate cancer research. PMID- 26883773 TI - Mimicking nature: Self-strengthening properties in a dental adhesive. AB - Chemical and enzymatic hydrolysis provoke a cascade of events that undermine methacrylate-based adhesives and the bond formed at the tooth/composite interface. Infiltration of noxious agents, e.g. enzymes, bacteria, and so forth, into the spaces created by the defective bond will ultimately lead to failure of the composite restoration. This paper reports a novel, synthetic resin that provides enhanced hydrolytic stability as a result of intrinsic reinforcement of the polymer network. The behavior of this novel resin, which contains gamma methacryloxyproyl trimethoxysilane (MPS) as its Si-based compound, is reminiscent of self-strengthening properties found in nature. The efforts in this paper are focused on two essential aspects: the visible-light irradiation induced (photoacid-induced) sol-gel reaction and the mechanism leading to intrinsic self strengthening. The FTIR band at 2840cm(-1) corresponding to CH3 symmetric stretch in -Si-O-CH3 was used to evaluate the sol-gel reaction. Results from the real time FTIR indicated that the newly developed resin showed a limited sol-gel reaction (<5%) during visible-light irradiation, but after 48h dark storage, the reaction was over 65%. The condensation of methoxysilane mainly occurred under wet conditions. The storage moduli and glass transition temperature of the copolymers increased in wet conditions with the increasing MPS content. The cumulative amounts of leached species decreased significantly when the MPS containing adhesive was used. The results suggest that the polymethacrylate-based network, which formed first as a result of free radical initiated polymerization, retarded the photoacid-induced sol-gel reaction. The sol-gel reaction provided a persistent, intrinsic reinforcement of the polymer network in both neutral and acidic conditions. This behavior led to enhanced mechanical properties of the dental adhesives under conditions that simulate the wet, oral environment. STATEMENT OF SIGNIFICANCE: A self-strengthening dental adhesive system was developed through a dual curing process, which involves the free radical photopolymerization followed by slow hydrolysis and condensation (photoacid induced sol-gel reaction) of alkoxylsilane groups. The concept of "living" photoacid-induced sol-gel reaction with visible-light irradiation was confirmed in the polymer. The sol-gel reaction was retarded by the polymethacrylate network, which was generated first; the network extended the life and retained the activity of silanol groups. The self-strengthening behavior was evaluated by monitoring the mechanical properties of the hybrid copolymers under wet conditions. The present research demonstrates the sol-gel reaction in highly crosslinked network as a potentially powerful strategy to prolong the functional lifetime of engineered biomaterials in wet environments. PMID- 26883774 TI - Wide-range stiffness gradient PVA/HA hydrogel to investigate stem cell differentiation behavior. AB - Although stiffness-controllable substrates have been developed to investigate the effect of stiffness on cell behavior and function, the use of separate substrates with different degrees of stiffness, substrates with a narrow range stiffness gradient, toxicity of residues, different surface composition, complex fabrication procedures/devices, and low cell adhesion are still considered as hurdles of conventional techniques. In this study, a cylindrical polyvinyl alcohol (PVA)/hyaluronic acid (HA) hydrogel with a wide-range stiffness gradient (between ~20kPa and ~200kPa) and cell adhesiveness was prepared by a liquid nitrogen (LN2)-contacting gradual freezing-thawing method that does not use any additives or specific devices to produce the stiffness gradient hydrogel. From an in vitro cell culture using the stiffness gradient PVA/HA hydrogel, it was observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (~20kPa for nerve cell, ~40kPa for muscle cell, ~80kPa for chondrocyte, and ~190kPa for osteoblast). The PVA/HA hydrogel with a wide range of stiffness spectrum can be a useful tool for basic studies related with the stem cell differentiation, cell reprogramming, cell migration, and tissue regeneration in terms of substrate stiffness. STATEMENT OF SIGNIFICANCE: It is postulated that the stiffness of the extracellular matrix influences cell behavior. To prove this concept, various techniques to prepare substrates with a stiffness gradient have been developed. However, the narrow ranges of stiffness gradient and complex fabrication procedures/devices are still remained as limitations. Herein, we develop a substrate (hydrogel) with a wide-range stiffness gradient using a gradual freezing-thawing method which does not need specific devices to produce a stiffness gradient hydrogel. From cell culture experiments using the hydrogel, it is observed that human bone marrow mesenchymal stem cells have favorable stiffness ranges for induction of differentiation into specific cell types (~20kPa for nerve, ~40kPa for muscle, ~80kPa for cartilage, and ~190kPa for bone in our hydrogel system). PMID- 26883775 TI - Extracellular matrix microarrays to study inductive signaling for endoderm specification. AB - During tissue development, stem and progenitor cells are faced with fate decisions coordinated by microenvironmental cues. Although insights have been gained from in vitro and in vivo studies, the role of the microenvironment remains poorly understood due to the inability to systematically explore combinations of stimuli at a large scale. To overcome such restrictions, we implemented an extracellular matrix (ECM) array platform that facilitates the study of 741 distinct combinations of 38 different ECM components in a systematic, unbiased and high-throughput manner. Using embryonic stem cells as a model system, we derived definitive endoderm progenitors and applied them to the array platform to study the influence of ECM, including the interactions of ECM with growth factor signaling, on the specification of definitive endoderm cells towards the liver and pancreas fates. We identified ECM combinations that influence endoderm fate decisions towards these lineages, and demonstrated the utility of this platform for studying ECM-mediated modifications to signal activation during liver specification. In particular, defined combinations of fibronectin and laminin isoforms, as well as combinations of distinct collagen subtypes, were shown to influence SMAD pathway activation and the degree of hepatic differentiation. Overall, our systematic high-throughput approach suggests that ECM components of the microenvironment have modulatory effects on endoderm differentiation, including effects on lineage fate choice and cell adhesion and survival during the differentiation process. This platform represents a robust tool for analyzing effects of ECM composition towards the continued improvement of stem cell differentiation protocols and further elucidation of tissue development processes. STATEMENT OF SIGNIFICANCE: Cellular microarrays can provide the capability to perform high-throughput investigations into the role of microenvironmental signals in a variety of cell functions. This study demonstrates the utility of a high-throughput cellular microarray approach for analyzing the effects of extracellular matrix (ECM) in liver and pancreas differentiation of endoderm progenitor cells. Despite an appreciation that ECM is likely involved in these processes, the influence of ECM, particularly combinations of matrix proteins, had not been systematically explored. In addition to the identification of relevant ECM compositions, this study illustrates the capability of the cellular microarray platform to be integrated with a diverse range of cell fate measurements, which could be broadly applied towards the investigation of cell fate regulation in other tissue development and disease contexts. PMID- 26883777 TI - Caffeine intake and myocardial perfusion imaging. PMID- 26883776 TI - Caffeine reduces the sensitivity of vasodilator MPI for the detection of myocardial ischaemia: Pro. AB - Caffeine is a non-selective antagonist at the adenosine receptors, which is expected to reverse both the intended (coronary vasodilation) and unintended (hypotension, flushing) effects of exogenously administered adenosine and adenosine-related compounds. In the past, several studies were conducted to characterize the effect of caffeine on vasodilator myocardial perfusion imaging (MPI) with conflicting results. However, new evidence supports earlier observations and shows that recent caffeine intake attenuates vasodilator-induced myocardial hyperaemia and may therefore reduce the sensitivity of radionuclide MPI for the detection of inducible perfusion abnormality in patients with coronary artery disease. Although the magnitude of this effect and hence its clinical significance are dose dependent, the acute response to equivalent doses of caffeine varies largely among individuals, and this might be explained by differences in caffeine exposure and genetically determined variations in caffeine metabolism. Abstinence from caffeinated foods and beverages for a minimum of 12 hours before vasodilator stress is therefore recommended although longer abstention might be required in order to prevent the potentially blocking effect of residual caffeine on vasodilator-mediated actions. PMID- 26883778 TI - The judgement of the eye. PMID- 26883779 TI - Erratum to: Not black or white, but brown: A common finding explained! PMID- 26883780 TI - Erratum to: Moving ahead with CZT technology. PMID- 26883781 TI - Myocardial perfusion SPECT just keeps getting better and better. PMID- 26883782 TI - Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines. AB - The Lewis acid MgCl2 allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl.LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn.2LiCl.2MgCl2 occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn.2LiCl.2MgCl2 also allows to functionalize cytidine derivatives at the position C(6). PMID- 26883783 TI - Percutaneous biopsy in the abdomen and pelvis: a step-by-step approach. AB - Percutaneous abdominal biopsies provide referring physicians with valuable diagnostic and prognostic information that guides patient care. All biopsy procedures follow a similar process that begins with the preprocedure evaluation of the patient and ends with the postprocedure management of the patient. In this review, a step-by-step approach to both routine and challenging abdominal biopsies is covered with an emphasis on the differences in biopsy devices and imaging guidance modalities. Adjunctive techniques that may facilitate accessing a lesion in a difficult location or reduce procedure risk are described. An understanding of these concepts will help maintain the favorable safety profile and high diagnostic yield associated with percutaneous biopsies. PMID- 26883784 TI - Managing risks in drug discovery: reproducibility of published findings. AB - In spite of tremendous advances in biopharmaceutical science and technology, the productivity of pharmaceutical research and development has been steadily declining over the last decades. The reasons for this decline are manifold and range from improved standard of care that is more and more difficult to top to inappropriate management of technical and translational risks along the R&D value chain. In this short review, major types of risks in biopharmaceutical R&D and means to address them will be described. A special focus will be on a risk, i.e., the lack of reproducibility of published information, that has so far not been fully appreciated and systematically analyzed. Measures to improve reproducibility and trust in published information will be discussed. PMID- 26883785 TI - Absence of bilateral C2 pars in a child with osteogenesis imperfecta. PMID- 26883786 TI - Healthcare Provider Type and Switch to Biologics in Psoriasis: Evidence from Real World Practice. AB - BACKGROUND: Previous research indicates an uneven uptake of biologics in patients with moderate-to-severe psoriasis in Sweden. Therefore, it is essential to scrutinise variations in treatment patterns. OBJECTIVE: The aim of this study was to evaluate the extent to which the uptake of biologics for psoriasis differs between types of healthcare provider. METHODS: Three types of provider were identified within 52 units participating in the Swedish National Registry for Systemic Psoriasis Treatment (PsoReg): university hospitals, non-university hospitals and individual practices. Biologics-naive patients (n = 3165) were included in analyses to investigate the probability of switch to biologics. The numbers of patients fulfilling the criteria for moderate-to-severe psoriasis [Psoriasis Area and Severity Index (PASI) >=10 and Dermatology Life Quality Index (DLQI) >=10] among patients who switched to biologics and patients who did not switch were reported. A logistic regression model was used to calculate how healthcare provider type influenced the probability of switch to biologics whilst adjusting for patient characteristics and disease severity. RESULTS: During registration, 16% of patients switched to biologics while 84% remained on conventional systemic treatment. In 7% of patients, the criteria PASI >=10 and DLQI >=10 was fulfilled at their last visit without switching to biologics, whereas in 10% of patients the criteria was not fulfilled prior to switch. After controlling for patient characteristics and disease severity, small or no difference in the probability of switch was observed between provider types. CONCLUSIONS: Disease severity does not explain the decision to switch or not to switch to biologics for a disproportionate number of patients. There seems to be an uneven uptake of biologics in Swedish clinical practice, but the type of healthcare provider cannot explain this variation. More research is needed on what factors influence the prescription of biologics. PMID- 26883787 TI - Rolling stones and turbulent eddies: why the bigger live longer and travel farther. AB - Here we report the discovery that even the simplest, oldest and most prevalent forms of evolutionary movement--rolling bodies and whirls of turbulence--exhibit the same body-size effect on life time and life travel as the evolutionary movement united by the body-size effect so far: animals, rivers, vehicles, jets and plumes. In short, the bigger should last longer and travel farther. For rolling bodies, the life span (t) and the life travel (L) should increase with the body mass (M) raised to the powers 1/6 and 1/3, respectively. The number of rolls during this movement is constant, independent of body size. For an eddy of turbulence, t should increase with the eddy mass (M) raised to the power 2/3, while L should increase with M(2/3) times the bulk speed of the turbulent stream that carries the eddy. The number of rolls during the eddy life span is a constant independent of eddy size. PMID- 26883789 TI - In Situ Visualization of Lithium Ion Intercalation into MoS2 Single Crystals using Differential Optical Microscopy with Atomic Layer Resolution. AB - Atomic-level visualization of the intercalation of layered materials, such as metal chalcogenides, is of paramount importance in the development of high performance batteries. In situ images of the dynamic intercalation of Li ions into MoS2 single-crystal electrodes were acquired for the first time, under potential control, with the use of a technique combining laser confocal microscopy with differential interference microscopy. Intercalation proceeded via a distinct phase separation of lithiated and delithiated regions. The process started at the atomic steps of the first layer beneath the selvedge and progressed in a layer-by-layer fashion. The intercalated regions consisted of Li ion channels into which the newly inserted Li ions were pushed atom-by-atom. Interlayer diffusion of Li ions was not observed. Deintercalation was also clearly imaged and was found to transpire in a layer-by-layer mode. The intercalation and deintercalation processes were chemically reversible and can be repeated many times within a few atomic layers. Extensive intercalation of Li ions disrupted the atomically flat surface of MoS2 because of the formation of small lithiated domains that peeled off from the surface of the crystal. The current-potential curves of the intercalation and deintercalation processes were independent of the scan rate, thereby suggesting that the rate-determining step was not governed by Butler-Volmer kinetics. PMID- 26883788 TI - Regulation of scleraxis transcriptional activity by serine phosphorylation. AB - Cardiac fibroblasts are the major extracellular matrix producing cells in the heart. Our laboratory was the first to demonstrate that the transcription factor scleraxis induces collagen 1alpha2 expression in both cardiac fibroblasts and myofibroblasts. Here we identify a novel post-translational mechanism by which scleraxis activity is regulated and determine its effect on transcription of genes targeted by scleraxis. Putative serine phosphorylation sites on scleraxis were revealed by in silico analysis using motif prediction software. Mutation of key serine residues to alanine, which cannot be phosphorylated, significantly attenuated the expression of fibrillar type I collagen and myofibroblast marker genes that are normally induced by scleraxis. Down-regulation of collagen 1alpha2 expression was due to reduced binding of the non-phosphorylated scleraxis mutant to specific E-box DNA-binding sites within the promoter as determined by chromatin immunoprecipitation in human cardiac myofibroblast cells and by electrophoretic mobility shift assay. This is the first evidence suggesting that scleraxis is phosphorylated under basal conditions. The phosphorylation sequence matched that targeted by Casein Kinase 2, and inhibition of this kinase activity disrupted the ability of scleraxis to modulate the expression of its target genes while also attenuating TGFbeta-induced expression of type I collagen and myofibroblast phenotype conversion marker genes. These results demonstrate a novel mechanism for regulation of scleraxis activity, which may prove to be tractable for pharmacologic manipulation. PMID- 26883790 TI - In-plane Isotropic Microwave Performance of CoZr Trilayer in GHz Range. AB - In this paper, we investigate the high frequency performance of Co90Zr10/SiO2/Co90Zr10 trilayers. It is demonstrated that the in-plane isotropic microwave performance is theoretically derived from the solution of the Landau Lifshitz-Gilbert equation and experimentally achieved in that sandwich structured film. The valuable isotropic behavior comes from the superposition of two uncouple ferromagnetic layers in which the uniaxial magnetic anisotropic fields are equivalent but mutually orthogonal. Moreover, the isotropic microwave performance can be tuned to higher resonance frequency up to 5.3 GHz by employing the oblique deposition technique. It offers a convenient and effective way to achieve an unusual in-plane isotropic microwave performance with high permeability in GHz, holding promising applications for the magnetic devices in the high frequency information technology. PMID- 26883791 TI - Controlled Immobilization Strategies to Probe Short Hyaluronan-Protein Interactions. AB - Well-controlled grafting of small hyaluronan oligosaccharides (sHA) enables novel approaches to investigate biological processes such as angiogenesis, immune reactions and cancer metastasis. We develop two strategies for covalent attachment of sHA, a fast high-density adsorption and a two-layer system that allows tuning the density and mode of immobilization. We monitored the sHA adlayer formation and subsequent macromolecular interactions by label-free quartz crystal microbalance with dissipation (QCM-D). The modified surfaces are inert to unspecific protein adsorption, and yet retain the specific binding capacity of sHA. Thus they are an ideal tool to study the interactions of hyaluronan-binding proteins and short hyaluronan molecules as demonstrated by the specific recognition of LYVE-1 and aggrecan. Both hyaladherins recognize sHA and the binding is independent to the presence of the reducing end. PMID- 26883792 TI - Experimental and Theoretical Studies of the Reactivity and Thermochemistry of Dicyanamide: N(CN)(2)(-). AB - Dicyanamide [N(CN)2(-)] is a common anionic component of ionic liquids, several of which have shown hypergolic reactivity upon mixing with white-fuming nitric acid. In this study, we explore the thermochemistry of dicyanamide and its reactivity with nitric acid and other molecules to gain insight into the initial stages of the hypergolic phenomenon. We have developed and utilized an electrospray ion source for our selected ion flow tube (SIFT) to generate the dicyanamide anion. We have explored the general reactivity of this ion with several neutral molecules and atoms. Dicyanamide does not show reactivity with O2, H2SO4, H2O2, DBr, HCl, NH3, N2O, SO2, COS, CO2, CH3OH, H2O, CH4, N2, CF4, or SF6 (k < 1 * 10(-12) cm(3)/s); moreover, dicyanamide does not react with N atom, O atom, or electronically excited molecular oxygen (k < 5 * 10(-12) cm(3)/s), and our previous studies showed no reactivity with H atom. However, at 0.45 Torr helium, we observe the adduct of dicyanamide with nitric acid with an effective bimolecular rate constant of 2.7 * 10(-10) cm(3)/s. Intrinsically, dicyanamide is a very stable anion in the gas phase, as illustrated by its lack of reactivity, high electron-binding energy, and low proton affinity. The lack of reactivity of dicyanamide with H2SO4 gives an upper limit for the gas-phase deprotonation enthalpy of the parent compound (HNCNCN; <310 +/- 3 kcal/mol). This limit is in agreement with theoretical calculations at the MP2/6-311++G(d,p) level of theory, finding that DeltaH298 K(HNCNCN) = 308.5 kcal/mol. Dicyanamide has two different proton acceptor sites. Experimental and computational results indicate that it is lower in energy to protonate the terminal nitrile nitrogen than the central nitrogen. Although proton transfer to dicyanamide was not observed for any of the acidic molecules investigated here, the calculations on dicyanamide with one to three nitric acid molecules reveal that higher-order solvation can favor exothermic proton transfer. Furthermore, the formation of 1,5-dinitrobiuret, proposed to be the key intermediate during the hypergolic ignition of dicyanamide ionic liquids with nitric acid, is investigated by calculation of the reaction coordinate. Our results suggest that solvation dynamics of dicyanamide with nitric acid play an important role in hypergolic ignition and the interactions at the droplet/condensed-phase surface between the two hypergolic liquids are very important. Moreover, dicyanamide exists in the atmosphere of Saturn's moon, Titan; the intrinsic stability of dicyanamide strongly suggests that it may exist in molecular clouds of the interstellar medium, especially in regions where other stable carbon-nitrogen anions have been detected. PMID- 26883794 TI - Review: changing (shared) heritability of ASD and ADHD across the lifespan. PMID- 26883793 TI - Effects of a worksite tobacco control intervention in India: the Mumbai worksite tobacco control study, a cluster-randomised trial. AB - OBJECTIVES: We assessed a worksite intervention designed to promote tobacco control among workers in the manufacturing sector in Greater Mumbai, India. METHODS: We used a cluster-randomised design to test an integrated health promotion/health protection intervention, the Healthy, Safe, and Tobacco-free Worksites programme. Between July 2012 and July 2013, we recruited 20 worksites on a rolling basis and randomly assigned them to intervention or delayed intervention control conditions. The follow-up survey was conducted between December 2013 and November 2014. RESULTS: The difference in 30-day quit rates between intervention and control conditions was statistically significant for production workers (OR=2.25, p=0.03), although not for the overall sample (OR=1.70; p=0.12). The intervention resulted in a doubling of the 6-month cessation rates among workers in the intervention worksites compared to those in the control, for production workers (OR=2.29; p=0.07) and for the overall sample (OR=1.81; p=0.13), but the difference did not reach statistical significance. CONCLUSIONS: These findings demonstrate the potential impact of a tobacco control intervention that combined tobacco control and health protection programming within Indian manufacturing worksites. TRIAL REGISTRATION NUMBER: NCT01841879. PMID- 26883795 TI - Blue Light Modulates Murine Microglial Gene Expression in the Absence of Optogenetic Protein Expression. AB - Neural optogenetic applications over the past decade have steadily increased; however the effects of commonly used blue light paradigms on surrounding, non optogenetic protein-expressing CNS cells are rarely considered, despite their simultaneous exposure. Here we report that blue light (450 nm) repetitively delivered in both long-duration boluses and rapid optogenetic bursts gene specifically altered basal expression of inflammatory and neurotrophic genes in immortalized and primary murine wild type microglial cultures. In addition, blue light reduced pro-inflammatory gene expression in microglia activated with lipopolysaccharide. These results demonstrate previously unreported, off-target effects of blue light in cells not expressing optogenetic constructs. The unexpected gene modulatory effects of blue light on wild type CNS resident immune cells have novel and important implications for the neuro-optogenetic field. Further studies are needed to elucidate the molecular mechanisms and potential therapeutic utility of blue light modulation of the wild type CNS. PMID- 26883798 TI - Sperm motility and viability extracted from penile tract of corpses: A preliminary study. AB - Posthumous sperm retrieval is a procedure in which spermatozoa are extracted from a man after he has been pronounced legally brain dead. Sperm retrieval from the penis has not been studied previously to the best of our knowledge. Our purpose was to determine the motility and viability of sperm from the penis with increasing time intervals from death. There was a progressive decrease in sperm motility with increasing post-mortem intervals, with a progressive increase in non-motility. Similarly, the sperm viability also showed a decreasing pattern with the increasing post-mortem interval. The sperm were found to be viable up to 24 h after death. Penile tract sperm retrieval has not been previously studied as far as we know. PMID- 26883796 TI - Disparities in suicide mortality trends between United States of America and 25 European countries: retrospective analysis of WHO mortality database. AB - The objective was to examine changes in temporal trends in suicide mortality in 26 Western countries by retrospective trend analysis of the WHO mortality database on causes of deaths. From 1990 to 2010, there was a median reduction in suicide mortality of 22.7%, ranging from a 46% reduction in Estonia to a 26.2% increase in Romania. Suicide mortality decreased by >= 20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1990. In most of the central European countries mortality strongly declined. The median changes in the age groups were -25.3% (range -62.9% to 72.6%) in people aged 15 24 years, -36.9% (-60.5% to 32.4%) in 25-34 years, -3.6% (-57.1% to 92%) in 35-54 years, -12.2% (-37% to 65,7%) in 55-74 years and -16.1% (-54.5% to 166.7%) in >= 75 years. Suicide prevention programs in youths and in the elderly seem to be effective (at least in females for the elderly) and efforts should be pursued in this way. However, suicide mortality of the people aged 35-54 years has increased in half of the studied countries between 1990 and 2010. Public policies should further orientate their efforts toward this population. PMID- 26883797 TI - Extraembryonic but not embryonic SUMO-specific protease 2 is required for heart development. AB - SUMO-specific protease 2 (SENP2) activities to remove SUMO from its substrates is essential for development of trophoblast stem cells, niches and lineages. Global deletion of SENP2 leads to midgestation lethality, and causes severe defects in the placenta which is accompanied by embryonic brain and heart abnormalities. Because of the placental deficiencies, the role of SENP2 in development of the embryonic tissues has not been properly determined. The brain and heart abnormalities may be secondary to placental insufficiency. Here we have created a new mouse strain permitting conditional inactivation of SENP2. Mice homozygous for germline deletion of the conditional allele exhibit trophoblast defects and embryonic abnormalities resembling the global SENP2 knockout. However, tissue specific disruptions of SENP2 demonstrate its dispensable role in embryogenesis. Placental expression of SENP2 is necessary and sufficient for embryonic heart and brain development. Using a protease deficient model, we further demonstrate the requirement of SENP2-dependent SUMO modification in development of all major trophoblast lineages. SENP2 regulates sumoylation of Mdm2 which controls p53 activities critical for G-S transition of mitotic division and endoreduplication in trophoblast proliferation and differentiation, respectively. The differentiation of trophoblasts is also dependent on SENP2-mediated activation of p57(Kip2), a CDK-specific inhibitor required for endoreduplication. PMID- 26883799 TI - The coevolution of overconfidence and bluffing in the resource competition game. AB - Resources are often limited, therefore it is essential how convincingly competitors present their claims for them. Beside a player's natural capacity, here overconfidence and bluffing may also play a decisive role and influence how to share a restricted reward. While bluff provides clear, but risky advantage, overconfidence, as a form of self-deception, could be harmful to its user. Still, it is a long-standing puzzle why these potentially damaging biases are maintained and evolving to a high level in the human society. Within the framework of evolutionary game theory, we present a simple version of resource competition game in which the coevolution of overconfidence and bluffing is fundamental, which is capable to explain their prevalence in structured populations. Interestingly, bluffing seems apt to evolve to higher level than corresponding overconfidence and in general the former is less resistant to punishment than the latter. Moreover, topological feature of the social network plays an intricate role in the spreading of overconfidence and bluffing. While the heterogeneity of interactions facilitates bluffing, it also increases efficiency of adequate punishment against overconfident behavior. Furthermore, increasing the degree of homogeneous networks can trigger similar effect. We also observed that having high real capability may accommodate both bluffing ability and overconfidence simultaneously. PMID- 26883800 TI - Kaempferol inhibits the growth and metastasis of cholangiocarcinoma in vitro and in vivo. AB - Kaempferol is a flavonoid that has been reported to exhibit antitumor activity in various malignant tumors. However, the role of kaempferol on cholangiocarcinoma (CCA) is largely unknown. In this article, we found that kaempferol inhibited proliferation, reduced colony formation ability, and induced apoptosis in HCCC9810 and QBC939 cells in vitro. Results from transwell assay and wound healing assay demonstrated that kaempferol significantly suppressed the migration and invasion abilities of HCCC9810 and QBC939 cells in vitro. Kaempferol was found to decrease the expression of Bcl-2 and increase the expressions of Bax, Fas, cleaved-caspase 3, cleaved-caspase 8, cleaved-caspase 9, and cleaved-PARP. In addition, kaempferol also downregulated the levels of phosphorylated AKT, TIMP2, and MMP2. In vivo, it was found that the volume of subcutaneous xenograft (0.15 cm(3)) in the kaempferol-treated group was smaller than that (0.6 cm(3)) in the control group. Kaempferol also suppressed the number and volume of metastasis foci in the lung metastasis model, with no marked effects on body weight of mice. Immunohistochemistry assay showed that the number of Ki-67-positive cells was lower in the kaempferol-treated group than that in the control group. We further confirmed that the changes of apoptosis- and invasion-related proteins after kaempferol treatment in vivo were similar to the results in vitro. These data suggest that kaempferol may be a promising candidate agent for the treatment of CCA. PMID- 26883802 TI - UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression. AB - Hyaluronan content is a powerful prognostic factor in many cancer types, but the molecular basis of its synthesis in cancer still remains unclear. Hyaluronan synthesis requires the transport of hyaluronan synthases (HAS1-3) from Golgi to plasma membrane (PM), where the enzymes are activated. For the very first time, the present study demonstrated a rapid recycling of HAS3 between PM and endosomes, controlled by the cytosolic levels of the HAS substrates UDP-GlcUA and UDP-GlcNAc. Depletion of UDP-GlcNAc or UDP-GlcUA shifted the balance towards HAS3 endocytosis, and inhibition of hyaluronan synthesis. In contrast, UDP-GlcNAc surplus suppressed endocytosis and lysosomal decay of HAS3, favoring its retention in PM, stimulating hyaluronan synthesis, and HAS3 shedding in extracellular vesicles. The concentration of UDP-GlcNAc also controlled the level of O-GlcNAc modification of HAS3. Increasing O-GlcNAcylation reproduced the effects of UDP-GlcNAc surplus on HAS3 trafficking, while its suppression showed the opposite effects, indicating that O-GlcNAc signaling is associated to UDP GlcNAc supply. Importantly, a similar correlation existed between the expression of GFAT1 (the rate limiting enzyme in UDP-GlcNAc synthesis) and hyaluronan content in early and deep human melanomas, suggesting the association of UDP sugar metabolism in initiation of melanomagenesis. In general, changes in glucose metabolism, realized through UDP-sugar contents and O-GlcNAc signaling, are important in HAS3 trafficking, hyaluronan synthesis, and correlates with melanoma progression. PMID- 26883801 TI - Chop Deficiency Protects Mice Against Bleomycin-induced Pulmonary Fibrosis by Attenuating M2 Macrophage Production. AB - C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop(-/-) mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor beta (TGF-beta) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-beta secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages. PMID- 26883803 TI - Maintaining memory of silencing at imprinted differentially methylated regions. AB - Imprinted genes are an exceptional cluster of genes which are expressed in a parent-of-origin dependent fashion. This allele-specific expression is dependent on differential DNA methylation which is established in the parental germlines in a sex-specific manner. The DNA methylation imprint is accompanied by heterochromatin modifications which must be continuously maintained through development. This review summarises the factors which are important for protecting the epigenetic modifications at imprinted differentially methylated regions (DMRs), including PGC7, ZFP57 and the ATRX/Daxx/H3.3 complex. We discuss how these factors maintain heterochromatin silencing, not only at imprinted DMRs, but also other heterochromatic regions in the genome. PMID- 26883805 TI - What Do We Mean by Accumulation? Advancing Conceptual Precision for a Core Idea in Gerontology. AB - In recent decades, the concept of accumulation has gained prominence in research on aging, health, and social stratification. Accumulation is now studied in multiple disciplines, revealing that cumulative processes are crucial to understanding patterns of differentiation over the life course. Although this research has demonstrated the empirical value of studying accumulation, the concept has taken on different and sometimes inconsistent meanings. To address these inconsistencies, we propose an interdisciplinary conceptual framework of accumulation that focuses on objects, timing, thresholds, de-accumulation, and the levels and consequences of accumulation. Providing a coherent framework of accumulation will aid conceptual precision, guide future research, and inform public policies related to aging and the life course. PMID- 26883804 TI - Neurotrophin signaling in cancer stem cells. AB - Cancer stem cells (CSCs), are thought to be at the origin of tumor development and resistance to therapies. Thus, a better understanding of the molecular mechanisms involved in the control of CSC stemness is essential to the design of more effective therapies for cancer patients. Cancer cell stemness and the subsequent expansion of CSCs are regulated by micro-environmental signals including neurotrophins. Over the years, the roles of neurotrophins in tumor development have been well established and regularly reviewed. Especially, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are reported to stimulate tumor cell proliferation, survival, migration and/or invasion, and favors tumor angiogenesis. More recently, neurotrophins have been reported to regulate CSCs. This review briefly presents neurotrophins and their receptors, summarizes their roles in different cancers, and discusses the emerging evidence of neurotrophins-induced enrichment of CSCs as well as the involved signaling pathways. PMID- 26883806 TI - Association of Hearing Impairment and Emotional Vitality in Older Adults. AB - OBJECTIVES: To better understand the potential impact of hearing impairment (HI) and hearing aid use on emotional vitality and mental health in older adults. METHOD: We investigated the cross-sectional association of HI with emotional vitality in 1,903 adults aged 76-85 years in the Health ABC study adjusted for demographic and cardiovascular risk factors. Hearing was defined by the speech frequency pure tone average (no impairment < 25 dB, mild impairment 25-40 dB, and moderate or greater impairment > 40 dB). Emotional vitality was defined as having a high sense of personal mastery, happiness, low depressive symptomatology, and low anxiety. RESULTS: Compared with individuals with no HI, participants with moderate or greater HI had a 23% lower odds of emotional vitality (odds ratio [OR] = 0.77; 95% confidence interval [CI]: 0.59-0.99). Hearing aid use was not associated with better emotional vitality (OR = 0.98; 95% CI: 0.81-1.20). DISCUSSION: HI is associated with lower odds of emotional vitality in older adults. Further studies are needed to examine the longitudinal impact of HI on mental health and well-being. PMID- 26883807 TI - The COBATEST network: a platform to perform monitoring and evaluation of HIV community-based testing practices in Europe and conduct operational research. AB - The European project "HIV community-based testing practices in Europe" (HIV COBATEST) has contributed to the establishment of a network of community-based voluntary counselling and testing services (CBVCTs) that monitors and evaluates HIV testing activity in the communities. The objective of this paper is to describe the data that have been collected during 2014 by the COBATEST network in order to provide an insight into testing activity of CBVCTs in Europe. Members of the CBVCT network share common instruments for data collection and data entry. The network has a common database that allows global data analysis and comparison between different centres. In 2014, 40 CBVCTs of 18 European countries were participating in the network, and, from those, 20 CBVCTs were using the common COBATEST data collection tools. In these 20 CBVCTs, a total of 9266 HIV screening tests were performed on 8554 people, of which 1.58% (135/8554) were reactive and 51.1% (69/135) confirmed positive. Five cases were false positives, and 84.1% (58/69) of the confirmed positive cases were linked to care. Most of the tested individuals were men (70.8%), between 21 and 35 years of age (57.6%) and natives (67.1%). A higher proportion of men who had sex with men (MSM) (38.8%; 3267/8554) were tested compared to heterosexual men (27.7%) and women (23.5%). Rapid blood test was used in 78.5% of the cases and mostly performed in CBVCT offices (88.3%). Among sex workers (SWs), the percentage of reactive screening tests was particularly high (4.0%), especially among male SWs (7.7%) as compared to other risk groups, such as MSM (3.1%). The COBATEST network contributes to the availability of standardized information about the activity and impact of CBVCT centres in Europe. This information and standardized tools can help improve these services and inform decision-makers to better contextualize these interventions within their national HIV-prevention programmes. PMID- 26883809 TI - Palladium Recovery in a H2-Based Membrane Biofilm Reactor: Formation of Pd(0) Nanoparticles through Enzymatic and Autocatalytic Reductions. AB - Recovering palladium (Pd) from waste streams opens up the possibility of augmenting the supply of this important catalyst. We evaluated Pd reduction and recovery as a novel application of a H2-based membrane biofilm reactor (MBfR). At steady states, over 99% of the input soluble Pd(II) was reduced through concomitant enzymatic and autocatalytic processes at acidic or near neutral pHs. Nanoparticulate Pd(0), at an average crystallite size of 10 nm, was recovered with minimal leaching and heterogeneously associated with microbial cells and extracellular polymeric substances in the biofilm. The dominant phylotypes potentially responsible for Pd(II) reduction at circumneutral pH were denitrifying beta-proteobacteria mainly consisting of the family Rhodocyclaceae. Though greatly shifted by acidic pH, the biofilm microbial community largely bounced back when the pH was returned to 7 within 2 weeks. These discoveries infer that the biofilm was capable of rapid adaptive evolution to stressed environmental change, and facilitated Pd recovery in versatile ways. This study demonstrates the promise of effective microbially driven Pd recovery in a single MBfR system that could be applied for the treatment of the waste streams, and it documents the role of biofilms in this reduction and recovery process. PMID- 26883808 TI - Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset. AB - BACKGROUND: Persistent low back pain is a significant problem worldwide. Early identification and treatment of individuals at high risk for persistent low back pain have been suggested as strategies to decrease the rate of disability associated with this condition. PURPOSE: To examine and compare demographic, pain related, psychological, and somatosensory characteristics in a cohort of participants with acute low back pain who later went on to experience persistent low back pain or whose pain resolved within the first 6 weeks after initial onset. METHODS: A descriptive study was conducted among men and women 18-50 years of age who had an acute episode of low back pain. Study questionnaires were administered to collect demographic information and measures of pain, coping, reactivity, mood, work history and satisfaction, and disability. A standardized protocol of quantitative sensory testing was performed on each participant at the painful area of their low back and at a remote site on their arm. RESULTS: The sample consisted of 48 participants, of whom 19 went on to develop persistent low back pain and 29 resolved. Compared to the resolved group, the persistent low back pain group was significantly older and had a lower level of educational attainment, a higher body mass index, and higher mean "least" pain score on the Brief Pain Inventory-Short Form. Significantly higher thermal detection thresholds at the painful and remote sites as well as signs of central sensitivity differentiated the persistent pain group from the resolved group during the acute stage of low back pain. PMID- 26883810 TI - Varying levels of difficulty index of skills-test items randomly selected by examinees on the Korean emergency medical technician licensing examination. AB - PURPOSE: The goal of this study was to characterize the difficulty index of the items in the skills test components of the class I and II Korean emergency medical technician licensing examination (KEMTLE), which requires examinees to select items randomly. METHODS: The results of 1,309 class I KEMTLE examinations and 1,801 class II KEMTLE examinations in 2013 were subjected to analysis. Items from the basic and advanced skills test sections of the KEMTLE were compared to determine whether some were significantly more difficult than others. RESULTS: In the class I KEMTLE, all 4 of the items on the basic skills test showed significant variation in difficulty index (P<0.01), as well as 4 of the 5 items on the advanced skills test (P<0.05). In the class II KEMTLE, 4 of the 5 items on the basic skills test showed significantly different difficulty index (P<0.01), as well as all 3 of the advanced skills test items (P<0.01). CONCLUSION: In the skills test components of the class I and II KEMTLE, the procedure in which examinees randomly select questions should be revised to require examinees to respond to a set of fixed items in order to improve the reliability of the national licensing examination. PMID- 26883811 TI - Calibrating the Medical Council of Canada's Qualifying Examination Part I using an integrated item response theory framework: a comparison of models and designs. AB - PURPOSE: The aim of this research was to compare different methods of calibrating multiple choice question (MCQ) and clinical decision making (CDM) components for the Medical Council of Canada's Qualifying Examination Part I (MCCQEI) based on item response theory. METHODS: Our data consisted of test results from 8,213 first time applicants to MCCQEI in spring and fall 2010 and 2011 test administrations. The data set contained several thousand multiple choice items and several hundred CDM cases. Four dichotomous calibrations were run using BILOG MG 3.0. All 3 mixed item format (dichotomous MCQ responses and polytomous CDM case scores) calibrations were conducted using PARSCALE 4. RESULTS: The 2-PL model had identical numbers of items with chi-square values at or below a Type I error rate of 0.01 (83/3,499 or 0.02). In all 3 polytomous models, whether the MCQs were either anchored or concurrently run with the CDM cases, results suggest very poor fit. All IRT abilities estimated from dichotomous calibration designs correlated very highly with each other. IRT-based pass-fail rates were extremely similar, not only across calibration designs and methods, but also with regard to the actual reported decision to candidates. The largest difference noted in pass rates was 4.78%, which occurred between the mixed format concurrent 2-PL graded response model (pass rate= 80.43%) and the dichotomous anchored 1-PL calibrations (pass rate= 85.21%). CONCLUSION: Simpler calibration designs with dichotomized items should be implemented. The dichotomous calibrations provided better fit of the item response matrix than more complex, polytomous calibrations. PMID- 26883812 TI - Organic nanophotonic materials: the relationship between excited-state processes and photonic performances. AB - Nanophotonics have recently captured broad attention because of their great potential in information processing and communication, which may allow rates and bandwidth beyond what is feasible in the realm of electronics. Organic materials could be well suitable for such applications due to their ability to generate, transmit, modulate and detect light in their lightweight and flexible nanoarchitectures. Their distinct nanophotonic properties strongly depend on their extrinsic morphologies and intrinsic molecular excited-state processes. In this feature article, we mainly focus on a comprehensive understanding of the relationship between molecular excited-state processes and the advanced photonic functionalities of organic micro/nano-crystals in recent organic nanophotonic research, and then expect to provide enlightenment for the design and development of tiny photonic devices with broadband tunable properties by tailoring the excited-state processes of organic microcrystals. PMID- 26883813 TI - Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen. AB - BACKGROUND: In an earlier study we developed a unique strategy allowing us to specifically eliminate antigen-specific murine B cells via their distinct B cell receptors using a new class of fusion proteins. In the present work we elaborated our idea to demonstrate the feasibility of specifically addressing and eliminating human memory B cells. RESULTS: The present study reveals efficient adaptation of the general approach to selectively target and eradicate human memory B cells. In order to demonstrate the feasibility we engineered a fusion protein following the principle of recombinant immunotoxins by combining a model antigen (tetanus toxoid fragment C, TTC) for B cell receptor targeting and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA') to induce apoptosis after cellular uptake. The TTC-ETA' fusion protein not only selectively bound to a TTC-reactive murine B cell hybridoma cell line in vitro but also to freshly isolated human memory B cells from immunized donors ex vivo. Specific toxicity was confirmed on an antigen-specific population of human CD27(+) memory B cells. CONCLUSIONS: This protein engineering strategy can be used as a generalized platform approach for the construction of therapeutic fusion proteins with disease-relevant antigens as B cell receptor-binding domains, offering a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases. PMID- 26883814 TI - Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. AB - The broad-spectrum herbicide glyphosate (common trade name "Roundup") was first sold to farmers in 1974. Since the late 1970s, the volume of glyphosate-based herbicides (GBHs) applied has increased approximately 100-fold. Further increases in the volume applied are likely due to more and higher rates of application in response to the widespread emergence of glyphosate-resistant weeds and new, pre harvest, dessicant use patterns. GBHs were developed to replace or reduce reliance on herbicides causing well-documented problems associated with drift and crop damage, slipping efficacy, and human health risks. Initial industry toxicity testing suggested that GBHs posed relatively low risks to non-target species, including mammals, leading regulatory authorities worldwide to set high acceptable exposure limits. To accommodate changes in GBH use patterns associated with genetically engineered, herbicide-tolerant crops, regulators have dramatically increased tolerance levels in maize, oilseed (soybeans and canola), and alfalfa crops and related livestock feeds. Animal and epidemiology studies published in the last decade, however, point to the need for a fresh look at glyphosate toxicity. Furthermore, the World Health Organization's International Agency for Research on Cancer recently concluded that glyphosate is "probably carcinogenic to humans." In response to changing GBH use patterns and advances in scientific understanding of their potential hazards, we have produced a Statement of Concern drawing on emerging science relevant to the safety of GBHs. Our Statement of Concern considers current published literature describing GBH uses, mechanisms of action, toxicity in laboratory animals, and epidemiological studies. It also examines the derivation of current human safety standards. We conclude that: (1) GBHs are the most heavily applied herbicide in the world and usage continues to rise; (2) Worldwide, GBHs often contaminate drinking water sources, precipitation, and air, especially in agricultural regions; (3) The half life of glyphosate in water and soil is longer than previously recognized; (4) Glyphosate and its metabolites are widely present in the global soybean supply; (5) Human exposures to GBHs are rising; (6) Glyphosate is now authoritatively classified as a probable human carcinogen; (7) Regulatory estimates of tolerable daily intakes for glyphosate in the United States and European Union are based on outdated science. We offer a series of recommendations related to the need for new investments in epidemiological studies, biomonitoring, and toxicology studies that draw on the principles of endocrinology to determine whether the effects of GBHs are due to endocrine disrupting activities. We suggest that common commercial formulations of GBHs should be prioritized for inclusion in government led toxicology testing programs such as the U.S. National Toxicology Program, as well as for biomonitoring as conducted by the U.S. Centers for Disease Control and Prevention. PMID- 26883815 TI - Characterising timing and pattern of relapse following surgery for localised oesophagogastric adenocarcinoma: a retrospective study. AB - BACKGROUND: Oesophagogastric adenocarcinoma (OGA) has a poor prognosis, even for patients with operable disease. However, the optimal surveillance strategy following surgery is unknown. METHODS: We performed a retrospective review of all patients with OGA who had undergone surgery with radical intent at the Royal Marsden between January 2001 and December 2010. RESULTS: Of the 360 patients with OGA who underwent potentially curative surgery, 100/214 patients (47%) with oesophageal/gastro-oesophageal junction (GOJ) adenocarcinoma and 47/146 patients (32%) with gastric adenocarcinoma developed recurrent disease. 51, 79 and 92% of relapses occurred within 1, 2 and 3 years respectively and the majority of patients relapsed at distant sites. Of the patients who relapsed, 67% (67/100) with oesophageal/GOJ adenocarcinoma and 72% of patients with gastric cancer (34/47) were symptomatic at the time of relapse. The majority of asymptomatic relapses were first detected by a rise in tumour markers. There was no difference in disease-free survival between asymptomatic and symptomatic patients, but asymptomatic patients were more likely to receive further treatment and had a longer survival beyond relapse. CONCLUSION: The majority of relapses occur within the first 3 years and at distant sites. Monitoring of tumour markers should be considered as part of a surveillance program. PMID- 26883816 TI - Factors associated with depressive symptoms in young long-term breast cancer survivors. AB - PURPOSE: Long-term breast cancer survivors frequently report distress (i.e., depressive symptoms) that impacts their quality of life. Previous studies have found that negative social interactions ("social constraints") from partners contribute to long-term, unresolved cycling of intrusive thoughts and cognitive avoidance, resulting in psychological distress. However, these relationships have not been tested in long-term breast cancer survivors. Furthermore, the effect of partners' depressive symptoms on the survivors' depressive symptoms has not been tested within the context of these relationships. Therefore, the purpose of this study was to test relationships between breast cancer survivors' depressive symptoms and (1) social constraints, cognitive avoidance, and intrusive thoughts, and (2) partners' depressive symptoms. METHODS: Data were from a cross-sectional descriptive study of breast cancer survivors (N = 222) 3-8 years post-diagnosis and their partners, who completed surveys assessing demographic characteristics, social constraints, intrusive thoughts, cognitive avoidance, and depressive symptoms. Structural equation modeling confirmatory path analyses were conducted to determine significant relationships between survivors' depressive symptoms and all other variables. RESULTS: Our model fits the data well. Breast cancer survivors' depressive symptoms were predicted by social constraints and intrusive thoughts. The relationship between survivors' depressive symptoms and partners' depressive symptoms was close but not significant. CONCLUSIONS: As hypothesized, depressive symptoms were predicted by social constraints and intrusive thoughts. Further research is needed to understand the possible relationship between survivors' long-term depressive symptoms and cognitive avoidance and partners' depressive symptoms. Our findings highlight the negative impact of social constraints from partners on psychological outcomes in long-term breast cancer survivors. PMID- 26883818 TI - Home but still engaged: participation in social activities among the homebound. AB - PURPOSE: Participation in social and community activities that require leaving one's home is important to older adults; however, many older adults have difficulty or are unable to leave their dwellings, and little is known from national samples about issues related to remaining active outside the home or the barriers faced by these older adults. DESIGN AND METHODS: We used the National Health and Aging Trends Study, a nationally representative study of older adults (n = 7197), to understand the following: (1) the importance that homebound and semi-homebound adults place on involvement in social or community activities, (2) their current level of involvement, and (3) reported barriers to participation. RESULTS: Despite the heavy burden of functional limitations, depression, pain, and falls, homebound adults reported that activities outside the home were important to them ranging from 25.2 % (attend clubs) to 70.0 % (visit family). Similarly, semi-homebound older adults had a strong interest in such participation, including visiting friends and family (81.8 %), attending religious services (72.6 %), and going out for enjoyment (72.5 %). Many homebound adults reported health (42.9-64.1 % depending on the activity) and transportation (12.2-18.2 %) as barriers to participation. Semi-homebound adults also identified health (23.8-41.0 %) and transportation (6.5-10.2 %) as participation barriers. IMPLICATIONS: This information can be useful in designing community programs that will foster meaningful social and community engagement for older adults, which may improve their quality of life. PMID- 26883817 TI - Development of the Cardiac Surgery Patient Expectations Questionnaire (C-SPEQ). AB - PURPOSE: Some variability in recovery and outcomes after cardiac surgery may be influenced by psychosocial aspects not routinely captured. Preliminary evidence suggests patient expectations impact health status, but there is no specific measure of expectations for cardiac surgery. The purpose of this study was to adapt an expectations scale to cardiac surgery and assess the psychometric properties of the scale. METHODS: Before surgery, 93 patients awaiting non emergent cardiac surgery completed questionnaires, including the adapted Cardiac Surgery Patient Expectations Questionnaire (C-SPEQ). At 1 year after surgery, 68 patients completed questionnaires. RESULTS: Mean C-SPEQ score was 39.4 +/- 9.02, and scores were normally distributed (Cronbach's alpha = 0.86). Higher score indicated negative expectations. Higher presurgery C-SPEQ score was correlated with greater depression (r = 0.32, p = 0.01) and perceived stress (r = 0.36, p = 0.003), but not state anxiety (r = 0.18, p = 0.14), at one-year post-surgery. Higher C-SPEQ was associated with longer recovery time (B = 0.14, p = 0.006) and lower physical HRQL after surgery (B = -0.31, p = 0.005). Higher C-SPEQ was not related to greater odds for perioperative complications (OR 1.01, p = 0.68) or readmissions <30 days (OR 1.05, p = 0.31). C-SPEQ score was not related to survival. CONCLUSIONS: Adaptation of an expectations questionnaire to cardiac surgery patients was successful with acceptable reliability and validity. Negative expectations had a detrimental impact on recovery and HRQL following cardiac surgery but were not related to clinical outcomes. Although focus is mainly on improving clinical outcomes, there are opportunities to improve non clinical aspects of the patient experience. Presurgical education might better prepare patients, reduce negative expectations, and improve psychosocial outcomes after cardiac surgery. PMID- 26883819 TI - Association between interleukin-6 (G174C and C572G) promoter gene polymorphisms and risk of ischemic stroke in North Indian population: a case-control study. AB - BACKGROUND: Polymorphisms of G174C and C572G in the interleukin-6 (IL-6) promoter gene can affect both transcription and secretion of IL-6 and may be involved in inflammation related to and pathogenesis of ischemic stroke (IS). Whether these IL-6 gene polymorphisms are risk factors for IS or not, remains controversial. OBJECTIVE: The aim of this study was to determine the association between IL-6 G174C and C572G gene polymorphisms and susceptibility to ischemic stroke in North Indian Population. METHODS: Two hundred and fifty IS patients and 250 age- and sex-matched controls were studied. Genotyping was performed using SNaPshot method. Stroke was classified using Trial of Org 10172 in acute stroke treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between IL-6 (G174C and C572G) polymorphisms and risk of IS. RESULTS: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary life style and low socioeconomic status were found to be associated with the risk of IS. Conditional logistic regression analysis showed a significant association of IL-6 G174C with the risk of IS under dominant model (OR, 1.61; 95%CI, 1.0-2.4; P value 0.02) and allelic model (OR, 1.5; 95%CI, 1.0-2.1; P value 0.02). For IL-6 C572G, multivariate adjusted analysis showed a significant association with the risk of IS under dominant model for overall IS (OR, 1.81; 95%CI, 1.04-3.15; P value 0.03) and small vessel disease subtype of IS (OR, 2.8; 95%CI, 1.3-6.0; P value 0.006). CONCLUSION: Our results suggest that IL 6 (G174C) polymorphism is significantly associated with the risk of IS in North Indian population. However, IL-6 (C572G) polymorphism is found significantly associated with the risk of IS after adjusting the demographic and risk factors variables. Prospective studies with large sample size are required for independent validation. Our findings could be helpful in identifying individuals at increased risk for developing IS. PMID- 26883820 TI - CD22 and CD72 are inhibitory receptors dominantly expressed in B lymphocytes and regulate systemic autoimmune diseases : English version. PMID- 26883821 TI - Reinterpreting Long-Term Evolution Experiments: Is Delayed Adaptation an Example of Historical Contingency or a Consequence of Intermittent Selection? AB - Van Hofwegen et al. demonstrated that Escherichia coli rapidly evolves the ability to use citrate when long selective periods are provided (D. J. Van Hofwegen, C. J. Hovde, and S. A. Minnich, J Bacteriol 198:1022-1034, 2016, http://dx.doi.org/10.1128/JB.00831-15). This contrasts with the extreme delay (15 years of daily transfers) seen in the long-term evolution experiments of Lenski and coworkers. Their idea of "historical contingency" may require reinterpretation. Rapid evolution seems to involve selection for duplications of the whole cit locus that are too unstable to contribute when selection is provided in short pulses. PMID- 26883822 TI - Functional Dissection of the CroRS Two-Component System Required for Resistance to Cell Wall Stressors in Enterococcus faecalis. AB - Bacteria use two-component signal transduction systems (TCSs) to sense and respond to environmental changes via a conserved phosphorelay between a sensor histidine kinase and its cognate response regulator. The opportunistic pathogen Enterococcus faecalis utilizes a TCS comprised of the histidine kinase CroS and the response regulator CroR to mediate resistance to cell wall stresses such as cephalosporin antibiotics, but the molecular details by which CroRS promotes cephalosporin resistance have not been elucidated. Here, we analyzed mutants of E. faecalis carrying substitutions in CroR and CroS to demonstrate that phosphorylated CroR drives resistance to cephalosporins, and that CroS exhibits kinase and phosphatase activities to control the level of CroR phosphorylation in vivo. Deletion of croS in various lineages of E. faecalis revealed a CroS independent mechanism for CroR phosphorylation and led to the identification of a noncognate histidine kinase capable of influencing CroR (encoded by OG1RF_12162; here called cisS). Further analysis of this TCS network revealed that both systems respond to cell wall stress. IMPORTANCE: TCSs allow bacteria to sense and respond to many different environmental conditions. The opportunistic pathogen Enterococcus faecalis utilizes the CroRS TCS to mediate resistance to cell wall stresses, including clinically relevant antibiotics such as cephalosporins and glycopeptides. In this study, we use genetic and biochemical means to investigate the relationship between CroRS signaling and cephalosporin resistance in E. faecalis cells. Through this, we uncovered a signaling network formed between the CroRS TCS and a previously uncharacterized TCS that also responds to cell wall stress. This study provides mechanistic insights into CroRS signaling and cephalosporin resistance in E. faecalis. PMID- 26883823 TI - Formate Metabolism in Shewanella oneidensis Generates Proton Motive Force and Prevents Growth without an Electron Acceptor. AB - Shewanella oneidensis strain MR-1 is a facultative anaerobe that thrives in redox stratified environments due to its ability to utilize a wide array of terminal electron acceptors. Conversely, the electron donors utilized by S. oneidensis are more limited and include products of primary fermentation such as lactate, pyruvate, formate, and hydrogen. Lactate, pyruvate, and hydrogen metabolisms inS. oneidensis have been described previously, but little is known about the role of formate oxidation in the ecophysiology of these bacteria. Formate is produced by S. oneidensis through pyruvate formate lyase during anaerobic growth on carbon sources that enter metabolism at or above the level of pyruvate, and the genome contains three gene clusters predicted to encode three complete formate dehydrogenase complexes. To determine the contribution of each complex to formate metabolism, strains lacking one, two, or all three annotated formate dehydrogenase gene clusters were generated and examined for growth rates and yields on a variety of carbon sources. Here, we report that formate oxidation contributes to both the growth rate and yield of S. oneidensis through the generation of proton motive force. Exogenous formate also greatly accelerated growth on N-acetylglucosamine, a carbon source normally utilized very slowly by S. oneidensis under anaerobic conditions. Surprisingly, deletion of all three formate dehydrogenase gene clusters enabled growth of S. oneidensis using pyruvate in the absence of a terminal electron acceptor, a mode of growth never before observed in these bacteria. Our results demonstrate that formate oxidation is a fundamental strategy under anaerobic conditions for energy conservation inS. oneidensis. IMPORTANCE: Shewanella species have garnered interest in biotechnology applications for their ability to respire extracellular terminal electron acceptors, such as insoluble iron oxides and electrodes. While much effort has gone into studying the proteins for extracellular electron transport, how electrons generated through the oxidation of organic carbon sources enter this pathway remains understudied. Here, we quantify the role of formate oxidation in the anaerobic physiology of Shewanella oneidensis Formate oxidation contributes to both the growth rate and yield on a variety of carbon sources through the generation of proton motive force. Advances in our understanding of the anaerobic metabolism of S. oneidensis are important for our ability to utilize and engineer this organism for applications in bioenergy, biocatalysis, and bioremediation. PMID- 26883825 TI - Contributions of Sinorhizobium meliloti Transcriptional Regulator DksA to Bacterial Growth and Efficient Symbiosis with Medicago sativa. AB - The stringent response, mediated by the (p)ppGpp synthetase RelA and the RNA polymerase-binding protein DksA, is triggered by limiting nutrient conditions. For some bacteria, it is involved in regulation of virulence. We investigated the role of two DksA-like proteins from the Gram-negative nitrogen-fixing symbiont Sinorhizobium meliloti in free-living culture and in interaction with its host plant Medicago sativa The two paralogs, encoded by the genes SMc00469 and SMc00049, differ in the constitution of two major domains required for function in canonical DksA: the DXXDXA motif at the tip of a coiled-coil domain and a zinc finger domain. Using mutant analyses of single, double, and triple deletions for SMc00469(designated dksA),SMc00049, and relA, we found that the DeltadksA mutant but not the DeltaSMc00049 mutant showed impaired growth on minimal medium, reduced nodulation on the host plant, and lower nitrogen fixation activity in early nodules, while its nod gene expression was normal. The DeltarelA mutant showed severe pleiotropic phenotypes under all conditions tested. Only S. meliloti dksA complemented the metabolic defects of an Escherichia coli dksA mutant. Modifications of the DXXDXA motif in SMc00049 failed to establish DksA function. Our results imply a role for transcriptional regulator DksA in the S. meliloti-M. sativa symbiosis. IMPORTANCE: The stringent response is a bacterial transcription regulation process triggered upon nutritional stress.Sinorhizobium meliloti, a soil bacterium establishing agriculturally important root nodule symbioses with legume plants, undergoes constant molecular adjustment during host interaction. Analyzing the components of the stringent response in this alphaproteobacterium helps understand molecular control regarding the development of plant interaction. Using mutant analyses, we describe how the lack of DksA influences symbiosis with Medicago sativa and show that a second paralogous S. meliloti protein cannot substitute for this missing function. This work contributes to the field by showing the similarities and differences of S. meliloti DksA-like proteins to orthologs from other species, adding information to the diversity of the stringent response regulatory system. PMID- 26883824 TI - Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks. AB - Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress,M. tuberculosis is prepared for battle against the host defense and able to persist within the human population. PMID- 26883826 TI - A Functional Core of IncA Is Required for Chlamydia trachomatis Inclusion Fusion. AB - Chlamydia trachomatis is an obligate intracellular pathogen that is the etiological agent of a variety of human diseases, including blinding trachoma and sexually transmitted infections. Chlamydiae replicate within a membrane-bound compartment, termed an inclusion, which they extensively modify by the insertion of type III secreted proteins called Inc proteins. IncA is an inclusion membrane protein that encodes two coiled-coil domains that are homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) motifs. Recent biochemical evidence suggests that a functional core, composed of SNARE like domain 1 (SLD-1) and part of SNARE-like domain 2 (SLD-2), is required for the characteristic homotypic fusion of C. trachomatis inclusions in multiply infected cells. To verify the importance of IncA in homotypic fusion in Chlamydia, we generated an incA::bla mutant. Insertional inactivation of incA resulted in the formation of nonfusogenic inclusions, a phenotype that was completely rescued by complementation with full-length IncA. Rescue of homotypic inclusion fusion was dependent on the presence of the functional core consisting of SLD-1 and part of SLD-2. Collectively, these results confirm in vitro membrane fusion assays identifying functional domains of IncA and expand the genetic tools available for identification of chlamydia with a method for complementation of site-specific mutants. IMPORTANCE: Chlamydia trachomatis replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusions are nonfusogenic with vesicles in the endocytic pathway but, in multiply infected cells, fuse with each other to form a single large inclusion. This homotypic fusion is dependent upon the presence of a chlamydial inclusion membrane localized protein, IncA. Specificity of membrane fusion in eukaryotic cells is regulated by SNARE (soluble N-ethylmaleimide sensitive factor attachment receptor) proteins on the cytosolic face of vesicles and target membranes. IncA contains two SNARE-like domains. Newly developed genetic tools for the complementation of targeted mutants in C. trachomatis are used to confirm the minimal requirement of SNARE-like motifs necessary to promote the homotypic fusion of inclusions. PMID- 26883828 TI - Infracommunity crowding as an individual measure of interactive-isolationist degree of parasite communities: disclosing the effects of extrinsic and host factors. AB - BACKGROUND: Interactions between parasite species within a host play a fundamental role in shaping parasite communities that have been classified within a continuum between interactive and isolationist. Interactive communities are principally structured by interactions between parasite species, while isolationist communities are structured by processes independent of the presence of other parasite species. Assessing whether, and to what extent, parasite communities exist along this continuum has been challenging due to a lack of an index that quantifies the degree of interactivity. Moreover, the absence of an index at the individual host level has made it unfeasible to identify host and extrinsic factors that may influence the degree of interactivity of a parasite community. METHODS: Here we propose an infracommunity crowding index that can reflect the degree of interactivity of a parasite community within each individual. This index quantifies the mean number of parasites that the average parasite within a community is exposed to, including the different aspects of parasite communities important in determining the level of interactivity, i.e. total abundance, species richness and evenness. We applied this analytical approach to the abomasal parasite communities of three alpine ruminant species that are traditionally viewed as isolationist. RESULTS: The application of our index to abomasal parasite communities shows that the majority of parasites live in highly crowded communities, suggesting that these host species harbour interactive parasite communities. In addition, the infracommunity crowding was highly variable and influenced by the host species, as well as by the timing of sampling and host age and sex. CONCLUSIONS: Despite increasing evidence on the influence of interactions between parasite species in shaping infections, an analytical measure to quantify the degree of interactivity of parasite communities is lacking. Here we present a new analytical approach which, when applied to parasite communities, appears to be sensitive to both extrinsic and host factors, highlighting that the degree of interactivity is not a static and specific feature of host species, but rather a dynamical process that keeps evolving during host's life. The new index provides opportunities for further investigations aimed at revealing the determinants of parasite interactivity. PMID- 26883827 TI - Bacterial Cysteine-Inducible Cysteine Resistance Systems. AB - Cysteine donates sulfur to macromolecules and occurs naturally in many proteins. Because low concentrations of cysteine are cytotoxic, its intracellular concentration is stringently controlled. In bacteria, cysteine biosynthesis is regulated by feedback inhibition of the activities of serine acetyltransferase (SAT) and 3-phosphoglycerate dehydrogenase (3-PGDH) and is also regulated at the transcriptional level by inducing the cysteine regulon using the master regulator CysB. Here, we describe two novel cysteine-inducible systems that regulate the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for biotechnological, medical, and industrial purposes. One locus, designated ccdA(formerly PAJ_0331), encodes a novel cysteine-inducible cysteine desulfhydrase (CD) that degrades cysteine, and its expression is controlled by the transcriptional regulator encoded byccdR(formerly PAJ_0332 orybaO), located just upstream of ccdA The other locus, designated cefA (formerly PAJ_3026), encodes a novel cysteine-inducible cysteine efflux pump that is controlled by the transcriptional regulator cefR(formerly PAJ_3027), located just upstream of cefA To our knowledge, this is the first example where the expression of CD and an efflux pump is regulated in response to cysteine and is directly involved in imparting resistance to excess levels of cysteine. We propose that ccdA and cefA function as safety valves that maintain homeostasis when the intra- or extracellular cysteine concentration fluctuates. Our findings contribute important insights into optimizing the production of cysteine and related biomaterials by P. ananatis IMPORTANCE: Because of its toxicity, the bacterial intracellular cysteine level is stringently regulated at biosynthesis. This work describes the identification and characterization of two novel cysteine-inducible systems that regulate, through degradation and efflux, the cysteine resistance of Pantoea ananatis, a member of the family Enterobacteriaceae that shows great potential for producing substances useful for industrial purposes. We propose that this novel mechanism for sensing and regulating cysteine levels is a safety valve enabling adaptation to sudden changes in intra- or extracellular cysteine levels in bacteria. Our findings provide important insights into optimizing the production of cysteine and related biomaterials by P. ananatis and also a deep understanding of sulfur/cysteine metabolism and regulation in this plant pathogen and related bacteria. PMID- 26883830 TI - Correction: Photon upconversion: from two-photon absorption (TPA) to triplet triplet annihilation (TTA). AB - Correction for 'Photon upconversion: from two-photon absorption (TPA) to triplet triplet annihilation (TTA)' by Changqing Ye et al., Phys. Chem. Chem. Phys., 2016, DOI: . PMID- 26883829 TI - Patient Factors Associated with Extended Length of Stay in the Psychiatric Inpatient Units of a Large Urban County Hospital. AB - This case-control study identified patient-specific factors associated with the longest psychiatric inpatient lengths of stay (LOS) at a large urban county hospital. Subjects with LOS >= 60 days comprised the extended LOS (ELOS) case cohort. An equally-sized control cohort consisted of a random sample of inpatients with LOS <= 30 days. Chi square tests and t tests were conducted to determine differences between groups. Factors associated with ELOS included older age, cognitive impairment, higher number of medical conditions requiring medication, and violence during hospital stay. Initiatives focused on community placement of patients with these characteristics may reduce prolonged LOS at safety-net hospitals. PMID- 26883832 TI - Highly efficient electrochemiluminescence based on pyrazolecarboxylic metal organic framework. AB - A series of transition metal complexes with the ligands 3-pyrazoledicarboxylic acid (H2L(1)) and ethyl 1-(2-ethoxy-2-oxoethyl)-1H-pyrazole-3-carboxylate (epzc) have been synthesized. The epzc generated 1-(carboxymethyl)-1H-pyrazole-3 carboxylic acid (H2L(2)) by an in situ hydrothermal hydrolysis reaction, using a one-pot method. Simple mononuclear [Co(HL(1))2(H2O)2] (1) and [Ni(L(2))(H2O)4] (4), dinuclear [Ni2(L(1))2(H2O)6].H2O (2) and [Cu2(L(2))2(H2O)4] (5) and 2D frameworks [Cu2(L(1))2]n (3), [Co2(L(2))2(H2O)4]n (6) have been isolated. The structures have been established by single-crystal X-ray diffraction, and the complexes characterized by FT-IR, thermogravimetric analysis (TGA), PRXD, UV-Vis spectroscopy, and fluorescent spectroscopy. 1, 2, 4 and 4 were further assembled to form a supramolecular structure by hydrogen-bonding interactions and/or pi...pi stacking. 3 and 6 both possess a 2D network structure that is further interlinked via intermolecular hydrogen-bonding interactions. Most importantly, the complexes demonstrated highly intense electrochemiluminescence (ECL) in DMF solution. PMID- 26883836 TI - Effects of Sodium Fluoride on Lipid Peroxidation and PARP, XBP-1 Expression in PC12 Cell. AB - This study aims to clarify the molecular mechanism of fluorine exposure that leads to nerve injury. PC12 cells were treated with fluorine at different concentrations (0.5, 1.0, 1.5, and 2.0 mM). Cytoactivity was detected at different time points (2, 4, 6, 8, 12, 24, and 48 h). After 2 h, DCF was used to detect and mark the level of reactive oxygen species (ROS) within cells. After 24 h, cellular metamorphosis was observed using an inverted microscope. After 2 h, Hoechst-33342 was used to detect apoptosis. After 24 h, Western blot analysis was performed to detect apoptosis-related poly (ADP-ribose) polymerase (PARP) protein, p-elF, and expression of the endoplasmic reticulum stress-related X-box binding protein 1 (XBP-1). The results showed that Fluorine exposure resulted in a reduction of cell viability, which was negatively correlated with fluorine dose. Within certain fluorine exposure duration, the ROS level within the cell and the apoptotic level are linearly related to fluorine exposure level. XBP-1 and PARP protein are sensitive to variations in fluorine concentration, which indicates that oxidative stress from fluorine exposure can lead to apoptosis. XBP 1 and PARP may be the key proteins during the entire process. These results provide a valid basis for fluorine-induced free radical injury theory. PMID- 26883837 TI - Oxidative Stress and Cell Apoptosis in Caprine Liver Induced by Molybdenum and Cadmium in Combination. AB - To investigate the effects of co-exposure to molybdenum (Mo) and cadmium (Cd) on oxidative stress and cell apoptosis in caprine livers, 36 Boer goats were randomly divided into four groups with nine goats in each group. Three groups were randomly assigned with one of three oral treatments of CdCl2 (0.5 mg Cd kg( 1).BW) and [(NH4)6Mo7O24.4H2O] (15 mg Mo kg(-1).BW, 30 mg Mo kg(-1).BW, 45 mg Mo kg(-1).BW), while the control group received deionized water. Liver tissues on days 0, 25, and 50 were subjected to determine antioxidant activity indexes and the messenger RNA (mRNA) expression levels of ceruloplasmin (CP), cysteinyl aspartate-specific proteinase-3 (caspase-3), second mitochondria-derived activator of caspases (Smac), and cytochrome-C (Cyt-C) genes. The results showed that significant reductions were observed in total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) activities (P < 0.05), while activities or contents of malondialdehyde (MDA), nitric oxide (NO), and nitric oxide synthase (NOS) were increased (P < 0.05). The mRNA expression levels of CP, caspase-3, Smac, and Cyt-C genes were upregulated (P < 0.05). In addition, histopathological lesions showed different degrees of vacuolar degeneration and edematous and mitochondrial swelling. The results suggest that co-exposure to Mo and Cd could induce oxidative stress and cell apoptosis possibly associated with mitochondrial intrinsic pathway in goat liver and show possible synergistic effects between the two elements. PMID- 26883838 TI - Sub-second carbon-nanotube-mediated microwave sintering for high-conductivity silver patterns on plastic substrates. AB - A method of microwave sintering that is mediated by carbon nanotubes (CNTs) has been developed to obtain high-conductivity Ag patterns on the top of heat sensitive plastic substrates within a short time. The Ag patterns are printed on CNTs formed on plastic substrates and rapidly heated to a great extent by the heat transferred from the microwave-heated CNTs. The conductivity of the microwave-sintered Ag patterns reaches ~39% that of bulk Ag within 1 s without substrate deformation. Furthermore, microwave sintering enhances the adhesion of Ag patterns to the thermoplastic substrates because the sintering causes interfacial fusion between the Ag patterns and the substrates, and CNTs physically connect the patterns with the substrates. PMID- 26883839 TI - Visual object individuation occurs over object wholes, parts, and even holes. AB - Segmentation of the world into meaningful units has typically been described as object individuation, emphasizing the spatially disconnected quality that comes as a result of objecthood. This segmentation can occur rapidly, even in parallel for multiple objects. It remains unclear whether objecthood is a necessary requirement for parallel individuation, or whether target features in distinct locations, such as object parts, may also be individuated in parallel. In a series of six experiments, we used a rapid enumeration task to test whether subitizing, a phenomenon believed to result from parallel individuation, occurs over object parts. We found that subitizing and individuation occur over connected object parts as well as physically separate objects of varied shapes and sizes. We also observed subitizing when target items are indents, features intrinsic to the shape of the object, and when cues for occlusion were removed. The results of these studies suggest that parallel individuation is not bound to objecthood, and can occur over object parts existing in separate locations. PMID- 26883841 TI - [Cardiovascular disease risks in people with an intellectual disability: causes and interventions]. AB - Cardiovascular disease occurs as frequently in older people with intellectual disabilities as in the same aged general population. However, there are indications for underdiagnosis of myocardial infarction due to atypical or absent complaints. Obesity, diabetes and peripheral arterial disease are more common in this group than in the general population. Hypertension, metabolic syndrome and kidney disease occur as frequently as in the general population while hypercholesterolemia occurs less often. Cardiovascular disease risk factors are underdiagnosed in people with intellectual disabilities. This could be reduced by educating supporting staff and caregivers and systematic screening for cardiovascular risk factors by the general practitioner. The customary guidelines should be followed in the treatment of cardiovascular risk factors and cardiovascular disease. Lifestyle interventions and treatment of specific causal factors, such as the use of psychotropic drugs and chronic circadian rhythm disorders, require a specialised approach. PMID- 26883840 TI - Perception of temporal order during the attentional blink: Using stimulus salience to modulate prior entry. AB - When multiple targets are presented in rapid sequence, observers frequently confuse the order in which they were presented. The probability of order reversals is known to vary throughout the period of the attentional blink (AB), which refers to impairment in the perception of the second of two targets when it is presented within approximately 500 ms from the first. Our objective was to examine the principle of prior entry (in which perception of temporal order is said to be affected by the relative latency at which each target is processed) as a determinant of the perception of temporal order throughout the AB. In two experiments, three letter targets (T1, T2, T3) were inserted in a stream of digit distractors, with T3 always presented directly after T2. The T1-T2 lag was varied to assess the perception of T2-T3 temporal order throughout the period of the AB. Processing latency was manipulated by means of salience. In Experiment 1, salience of T2 and T3 was manipulated exogenously by coloring the salient target red with all other stimuli being green. In Experiment 2, salience was modulated endogenously by manipulating which of the two targets matched the contents of working memory. Consistent with the principle of prior entry, perception of temporal order in both experiments was enhanced throughout the period of the AB when T2 was salient, and impaired when T3 was salient. Simulations based on the Episodic Simultaneous Type, Serial Token (eSTST) model that incorporates prior entry, matched the empirical results. PMID- 26883842 TI - [A man with a painful index finger]. AB - A 52-year-old man presented with pain in his right index finger. No history of trauma was reported. His finger nails were dystrophic and the X-ray of the finger showed typical osteolysis of the distal phalanx of his right index finger. This was caused by acrodermatitis continua of Hallopeau. We administered naproxen, methotrexate and folic acid as a systemic anti-inflammatory treatment. PMID- 26883843 TI - [A woman with palpitations, dyspnoea and a heart murmur]. AB - A 35-year-old female came to the ER with palpations, dyspnoea and some thoracic chest pain. During physical examination we heard a diastolic murmur. Using transoesophageal echocardiography and MRI we made the diagnosis of congenital quadricuspid aortic valve (type A) with moderate aortic regurgitation. PMID- 26883845 TI - [A dyspnoeic boy with two round masses on his chest X-ray]. AB - A 5-year-old boy presented with vomiting and dyspnoea. His chest X-ray showed two round consolidations in his right lung, one of them with air bronchograms, which were caused by round pneumonia. Round pneumonia presents with multiple lesions in only 2% of cases. PMID- 26883844 TI - [Catatonic syndrome after single low dose of droperidol]. AB - BACKGROUND: Patients find postoperative nausea and vomiting extremely unpleasant. If nausea persists despite initial treatment, droperidol, a butyrophenone with anti-dopaminergic activity, can be very effective. Side-effects, albeit rare, can occur and are potentially serious. CASE DESCRIPTION: A 75-year-old postoperative patient was given a single low dose of droperidol to treat persistent nausea. Subsequently, the patient developed catatonic syndrome. The psychiatrist treated the patient with benzodiazepine and electroconvulsive therapy. Within four weeks the patient had completely recovered. CONCLUSION: Catatonic syndrome is a serious condition; morbidity and mortality are mainly influenced by disease duration and early initiation of appropriate treatment. Physicians are not familiar with this syndrome. Since other syndromes and diseases may display similar symptoms, the condition is difficult to diagnose. Even after a single, low dose of droperidol, patients can be at risk of developing catatonic syndrome. PMID- 26883846 TI - Nanotwin-governed toughening mechanism in hierarchically structured biological materials. AB - As a natural biocomposite, Strombus gigas, commonly known as the giant pink queen conch shell, exhibits outstanding mechanical properties, especially a high fracture toughness. It is known that the basic building block of conch shell contains a high density of growth twins with average thickness of several nanometres, but their effects on the mechanical properties of the shell remain mysterious. Here we reveal a toughening mechanism governed by nanoscale twins in the conch shell. A combination of in situ fracture experiments inside a transmission electron microscope, large-scale atomistic simulations and finite element modelling show that the twin boundaries can effectively block crack propagation by inducing phase transformation and delocalization of deformation around the crack tip. This mechanism leads to an increase in fracture energy of the basic building block by one order of magnitude, and contributes significantly to that of the overall structure via structural hierarchy. PMID- 26883848 TI - Restoration of bactericidal activity of neutrophils by myeloperoxidase release: A new perspective for preventing infection in alcoholic cirrhosis. PMID- 26883847 TI - Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes. AB - Chronic low-grade inflammation contributes to the pathology and complications of type 2 diabetes (T2D). Interleukin-10 (IL10), an anti-inflammatory cytokine, is suggested to play a protective role in T2D. However, the impact of T2D on IL10 function has not been previously assessed. We examined the ability of IL10 to inhibit inflammation in human T2D immune cells and explored underlying mechanisms using macrophage models. IL10 was less effective at inhibiting tumour necrosis factor (TNF)-alpha secretion in T2D whole blood cultures, which was not explained by altered IL10 receptor surface expression. These findings were observed in macrophages exposed to high glucose, which demonstrated similar IL10 resistance or hyporesponsiveness. These findings were also not explained by changes in IL10 receptor protein or other downstream signaling proteins. High glucose was also shown to impair the ability of IL10 to activate STAT3, a downstream signaling protein of IL10. Treatment with the SHIP1 agonist, AQX-MN100, reversed IL10 hyporesponsiveness in macrophages cultured in high glucose and showed equal effectiveness at different glucose conditions. This data supports the idea that IL10 hyporesponsiveness may contribute to chronic inflammation in T2D. These novel findings suggest that strategies aimed to overcome IL10 hyporesponsiveness may hold therapeutic potential for reducing inflammation in T2D. PMID- 26883849 TI - Management of large hepatocellular carcinoma by sequential transarterial chemoembolization and portal vein embolization: a systematic review of the literature. AB - INTRODUCTION: Currently, the treatment of HCC is multidisciplinary. Surgery remains the gold standard although the management of large hepatocellular carcinoma remains challenging. Hepatic resection is increasingly performed with ever-expanding indications. However, postoperative liver failure remains a major cause of death after major hepatic resections. The purpose of this review is to report the results of large hepatocellular carcinoma (>5 cm or more nodules in the same lobe) management using sequential transarterial chemoembolization (TACE) and portal vein embolization (PVE) before major liver resections. EVIDENCE ACQUISITION: A literature search was performed using PubMed, Scopus, and Web of Science (WoS) from cited English publications. The search was last conducted in December 2014. Search phrases included "hepatocellular carcinoma", "liver resection", "transarterial chemoembolization", and "portal vein embolization". Clinical and survival parameters were extracted. When there was more than one publication from the same surgical team and/or authors, only the last publication in chronological order was considered for the study. Case reports, abstracts, letters, editorials, and expert opinions were not considered for the drafting of the study. After application of selective criteria, only 4 original studies were analyzed. EVIDENCE SYNTHESIS: No meta-analyses were found in the search. Among the 4 selected publications, 3 originated from Asia and 1 from Europe. The total number of patients treated with the method considered was 171 (range: 18-71). The mean size of the tumor was >5 cm. The gain of volume of the future remnant liver (FRL) was higher in the group with TACE+PVE as compared to the group with PVE alone (12% vs. 8%). A major hepatectomy was carried out in 166 patients (97%). Mortality rate ranged between 0% and 11%. The 5-year overall survival was between 43% and 72% and the 5-year recurrence-free survival was between 37% and 61%. CONCLUSIONS: Sequential TACE+PVE prior to a major hepatectomy for HCC was feasible, safe, and with excellent 5-year overall survival rates reported to be between 43% and 72%. PMID- 26883850 TI - A multi-trait meta-analysis with imputed sequence variants reveals twelve QTL for mammary gland morphology in Fleckvieh cattle. AB - BACKGROUND: The availability of whole-genome sequence data from key ancestors in bovine populations provides an exhaustive catalogue of polymorphic sites that segregate within and across cattle breeds. Sequence variants identified from the sequenced genome of key ancestors can be imputed into animals that have been genotyped using medium- and high-density genotyping arrays. Association analysis with imputed sequences, particularly when applied to multiple traits simultaneously, is a very powerful approach to detect candidate causal variants that underlie complex phenotypes. RESULTS: We used whole-genome sequence data from 157 key ancestors of the German Fleckvieh cattle population to impute 20,561,798 sequence variants into 10,363 animals that had (partly imputed) genotypes based on 634,109 single nucleotide polymorphisms (SNPs). Rare variants were more frequent among the sequence-derived than the array-derived genotypes. Association studies with imputed sequence variants were performed using seven correlated udder conformation traits as response variables. The calculation of an approximate multi-trait test statistic enabled us to detect 12 quantitative trait loci (QTL) (P < 2.97 * 10(-9)) that affect different morphological features of the mammary gland. Among the tested variants, the most significant associations were found for imputed sequence variants at 11 QTL, whereas the top association signal was observed for an array-derived variant at a QTL on bovine chromosome 14. Seven QTL were associated with multiple phenotypes. Most QTL were located in non-coding regions of the genome but in close proximity of candidate genes that could be involved in mammary gland morphology (SP5, GC, NPFFR2, CRIM1, RXFP2, TBX5, RBM19 and ADAM12). CONCLUSIONS: Using imputed sequence variants in association analyses allows the detection of QTL at maximum resolution. Multi trait approaches can reveal QTL that are not detected in single-trait association studies. Most QTL for udder conformation traits were located in non-coding regions of the genome, which suggests that mutations in regulatory sequences are the major determinants of variation in mammary gland morphology in cattle. PMID- 26883851 TI - The relationship between erectile dysfunction and paroxysmal lone atrial fibrillation. AB - PURPOSE: Endothelial dysfunction plays a major role in erectile dysfunction (ED). Atrial fibrillation (AF), regardless of subtype, is associated with a prothrombotic state, which is related to endothelial dysfunction. In this study, we aimed to determine whether AF is an independent risk factor for ED. METHODS: A total of 50 patients diagnosed with paroxysmal lone AF and 80 age-, gender-, and body mass index-matched controls without AF who admitted to outpatient clinics at a tertiary center were enrolled. Diagnosis of ED was performed by using Sexual Health Inventory for Men (SHIM) questionnaire. Patients with a SHIM score <=21 were defined as having ED. RESULTS: Mean age of patients were 51.8 +/- 7.7 and all of the study population were male. Twenty-nine of 50 patients in lone AF group and 25 of 80 patients in control group were diagnosed with ED (58 vs 31.2 %, p = 0.002). Mean SHIM score was significantly lower in lone AF group compared with controls (20.74 +/- 2.67 vs 22.39 +/- 2.21, p < 0.001). The multivariate stepwise logistic regression analyses showed that lone AF (OR 1.94 (1.44-2.46), p < 0.001), smoking (OR 1.92 (1.35-2.44), p = 0.003), fasting blood glucose (OR 1.51 (1.10-1.85), p = 0.012), and uric acid levels (OR 1.56 (1.13-1.92), p = 0.009) were independent predictors of ED. CONCLUSIONS: Beat-to-beat variation may lead to ED in patients with paroxysmal lone AF and questioning erectile function in patients with lone AF may be recommended. PMID- 26883852 TI - Loss of potential reward is best motivator in workers' wellness programme, study finds. PMID- 26883853 TI - A practical approach for the scale-up of roller compaction process. AB - An alternative approach for the scale-up of ribbon formation during roller compaction was investigated, which required only one batch at the commercial scale to set the operational conditions. The scale-up of ribbon formation was based on a probability method. It was sufficient in describing the mechanism of ribbon formation at both scales. In this method, a statistical relationship between roller compaction parameters and ribbon attributes (thickness and density) was first defined with DoE using a pilot Alexanderwerk WP120 roller compactor. While the milling speed was included in the design, it has no practical effect on granule properties within the study range despite its statistical significance. The statistical relationship was then adapted to a commercial Alexanderwerk WP200 roller compactor with one experimental run. The experimental run served as a calibration of the statistical model parameters. The proposed transfer method was then confirmed by conducting a mapping study on the Alexanderwerk WP200 using a factorial DoE, which showed a match between the predictions and the verification experiments. The study demonstrates the applicability of the roller compaction transfer method using the statistical model from the development scale calibrated with one experiment point at the commercial scale. PMID- 26883854 TI - Econazole imprinted textiles with antifungal activity. AB - In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5+/-0.1 MUm). Using an optimized screen printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97+/-3 MUg/cm(2)) was reproducible and stable up to 4 months storage at 25 degrees C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8 degrees C, which enabled a larger drug release at 32 degrees C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl(r). ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl(r). Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. PMID- 26883856 TI - Recall criteria for ultrasound breast cancer screening. PMID- 26883855 TI - Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon beta signaling pathway. AB - Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD, which affects cloven-hoofed animals. The pathophysiology of FMDV has not been fully understood and the evasion of host innate immune system is still unclear. Here, the FMDV non-structural protein 3A was identified as a negative regulator of virus-triggered IFN-beta signaling pathway. Overexpression of the FMDV 3A inhibited Sendai virus-triggered activation of IRF3 and the expressions of RIG I/MDA5. Transient transfection and co-immunoprecipitation experiments suggested that FMDV 3A interacts with RIG-I, MDA5 and VISA, which is dependent on the N terminal 51 amino acids of 3A. Furthermore, 3A also inhibited the expressions of RIG-I, MDA5, and VISA by disrupting their mRNA levels. These results demonstrated that 3A inhibits the RLR-mediated IFN-beta induction and uncovered a novel mechanism by which the FMDV 3A protein evades the host innate immune system. PMID- 26883857 TI - Lobular Carcinoma in Situ with Atypical Mass Presentation: a Case Report. AB - Lobular carcinoma in situ (LCIS) is associated with an increased risk of breast cancer and accounts for 1 to 2% of all breast cancers. LCIS diagnosis currently remains one of the major identifiable risk factors for subsequent breast cancer development. Imaging methods are becoming increasingly sensitive, and the consequent detection of small lesions and subtle abnormalities increases the chance of detection of in situ and invasive carcinomas, leading to a reduction in mortality. This report describes a case of a palpable complaint with abnormal imaging findings, including a solid LCIS mass. PMID- 26883858 TI - Expression of the Immunohistochemical Markers p16 and Ki-67 and Their Usefulness in the Diagnosis of Cervical Intraepithelial Neoplasms. AB - OBJECTIVE: The aim of this study was to determine the expression of the immunohistochemical markers p16 and Ki-67 in cervical intraepithelial neoplasms and their influence on the level of agreement among different observers and for the same observer. METHODS: The study included 184 patients with cervical intraepithelial neoplasms previously confirmed through biopsies performed between 2005 and 2006. Three pathologists reviewed the biopsies by using hematoxylin eosin staining to reach a consensus on the diagnosis. Subsequently, an immunohistochemical study analyzed the expression of p16 and Ki-67 in such cases. RESULTS: The comparison among the reviewing pathologists revealed only moderate agreement (kappa = 0.44). The agreement improved when the differentiation of high grade lesions (cervical intraepithelial neoplasm - CIN - 3) was analyzed (kappa = 0.59). p16 staining exhibited a high negative predictive value and sensitivity; however, the specificity was low. Overall, both qualitative and quantitative analyses of p16 and a quantitative analysis Ki-67 exhibited low accuracy. The agreement among diagnoses before immunohistochemistry was 0.47. The use of immunohistochemistry increased the agreement to 0.68. CONCLUSION: Our study showed that the agreement among observers using traditional diagnostic criteria of cervical intraepithelial lesions can improve with the use of immunohistochemistry. PMID- 26883859 TI - Urine Pregnancy Test before Rubella Vaccination among Reproductive Age Females: An Observation. PMID- 26883861 TI - The Potential of Cesarean Section as a Causative Factor of Chronic Pelvic Pain. PMID- 26883860 TI - Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats. AB - OBJECTIVE: We studied the effects of loss of ovarian function (ovariectomy) on muscle mass of gastrocnemius and the mRNA levels of IGF-1, atrogin-1, MuRF-1, and myostatin in an experimental model of rheumatoid arthritis in rats. METHODS: We randomly allocated 24 female Wistar rats (9 weeks, 195.3 +/- 17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CT Sham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met-BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (DeltaDeltaCT). RESULTS: The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OV and RAOV groups, but not in the RA and Sham groups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups. CONCLUSION: Loss of ovarian function results in increased loss of skeletal muscle-related ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats. PMID- 26883863 TI - Quality Indicators of Cervical Cytopathology Tests in the Public Service in Minas Gerais, Brazil. AB - OBJECTIVE: The objective of this study is to assess the performance of cytopathology laboratories providing services to the Brazilian Unified Health System (Sistema Unico de Saude - SUS) in the State of Minas Gerais, Brazil. METHODS: This descriptive study uses data obtained from the Cervical Cancer Information System from January to December 2012. Three quality indicators were analyzed to assess the quality of cervical cytopathology tests: positivity index, percentage of atypical squamous cells (ASCs) in abnormal tests, and percentage of tests compatible with high-grade squamous intraepithelial lesions (HSILs). Laboratories were classified according to their production scale in tests per year <= 5,000; from 5,001 to 10,000; from 10,001 to 15,000; and >= 15,001. Based on the collection of variables and the classification of laboratories according to production scale, we created and analyzed a database using Microsoft Office Excel 97-2003. RESULTS: In the Brazilian state of Minas Gerais, 146 laboratories provided services to the SUS in 2012 by performing a total of 1,277,018 cervical cytopathology tests. Half of these laboratories had production scales <= 5,000 tests/year and accounted for 13.1% of all tests performed in the entire state; in turn, 13.7% of these laboratories presented production scales of > 15,001 tests/year and accounted for 49.2% of the total of tests performed in the entire state. The positivity indexes of most laboratories providing services to the SUS in 2012, regardless of production scale, were below or well below recommended limits. Of the 20 laboratories that performed more than 15,001 tests per year, only three presented percentages of tests compatible with HSILs above the lower limit recommended by the Brazilian Ministry of Health. CONCLUSION: The majority of laboratories providing services to the SUS in Minas Gerais presented quality indicators outside the range recommended by the Brazilian Ministry of Health. PMID- 26883862 TI - Impact of Sacrospinous Colpopexy Associated with Anterior Colporrhaphy for the Treatment of Dome Prolapse on all Three Vaginal Compartments. AB - OBJECTIVE: To evaluate the results of sacrospinous colpopexy surgery associated with anterior colporrhaphy for the treatment of women with post-hysterectomy vaginal vault prolapse. METHODS: This prospective study included 20 women with vault prolapse, Pelvic Organ Prolapse Quantification System (POP-Q) stage >= 2, treated between January 2003 and February 2006, and evaluated in a follow-up review (more than one year later). Genital prolapse was evaluated qualitatively in stages and quantitatively in centimeters. Prolapse stage < 2 was considered to be the cure criterion. Statistical analysis was performed using the Wilcoxon test (paired samples) to compare the points and stages of prolapse before and after surgery. RESULTS: Evaluation of the vaginal vault after one year revealed that 95% of subjects were in stage zero and that 5% were in stage 1. For cystocele, 50% were in stage 1, 10% were in stage 0 (cured) and 40% were in stage 2. For rectocele, three women were in stage 1 (15%), one was in stage 2 (5%) and 16 had no further prolapse. The most frequent complication was pain in the right buttock, with remission of symptoms in all three cases three months after surgery. CONCLUSIONS: In this retrospective study, the surgical correction of vault prolapse using a sacrospinous ligament fixation technique associated with anterior colporrhaphy proved effective in resolving genital prolapse. Despite the low complication rates, there was a high rate of cystocele, which may be caused by posterior vaginal shifting due to either the technique or an overvaluation by the POP-Q system. PMID- 26883864 TI - Conservative Treatment of Stress Urinary Incontinence: A Systematic Review with Meta-analysis of Randomized Controlled Trials. AB - We performed a systematic review and meta-analysis of randomized controlled trials that studied the conservative management of stress urinary incontinence (SUI). There were 1058 results after the initial searches, from which 37 studies were eligible according to previously determined inclusion criteria. For the primary outcomes, pelvic floor muscle training (PFMT) was more efficacious than no treatment in improving incontinence-specific quality of life (QoL) scales (SMD = -1.24SDs; CI 95% = -1.77 to -0.71SDs). However, its effect on pad tests was imprecise. Combining biofeedback with PFMT had an uncertain effect on QoL (MD = 4.4 points; CI 95% = -16.69 to 7.89 points), but better results on the pad test, although with elevated heterogeneity (MD = 0.9g; 95%CI = 0.71 to 1,10g); group PFMT was not less efficacious than individual treatment, and home PFMT was not consistently worse than supervised PFMT. Both intravaginal and superficial electrical stimulation (IES and SES) were better than no treatment for QoL and pad test. Vaginal cones had mixed results. The association of IES with PFMT may improve the efficacy of the latter for QoL and pad test, but the results of individual studies were not consistent. Thus, there is evidence of the use of PFMT on the treatment of SUI, with and without biofeedback. PMID- 26883865 TI - Wide distribution and altitude correlation of an archaic high-altitude-adaptive EPAS1 haplotype in the Himalayas. AB - High-altitude adaptation in Tibetans is influenced by introgression of a 32.7-kb haplotype from the Denisovans, an extinct branch of archaic humans, lying within the endothelial PAS domain protein 1 (EPAS1), and has also been reported in Sherpa. We genotyped 19 variants in this genomic region in 1507 Eurasian individuals, including 1188 from Bhutan and Nepal residing at altitudes between 86 and 4550 m above sea level. Derived alleles for five SNPs characterizing the core Denisovan haplotype (AGGAA) were present at high frequency not only in Tibetans and Sherpa, but also among many populations from the Himalayas, showing a significant correlation with altitude (Spearman's correlation coefficient = 0.75, p value 3.9 * 10(-11)). Seven East- and South-Asian 1000 Genomes Project individuals shared the Denisovan haplotype extending beyond the 32-kb region, enabling us to refine the haplotype structure and identify a candidate regulatory variant (rs370299814) that might be interacting in an additive manner with the derived G allele of rs150877473, the variant previously associated with high altitude adaptation in Tibetans. Denisovan-derived alleles were also observed at frequencies of 3-14% in the 1000 Genomes Project African samples. The closest African haplotype is, however, separated from the Asian high-altitude haplotype by 22 mutations whereas only three mutations, including rs150877473, separate the Asians from the Denisovan, consistent with distant shared ancestry for African and Asian haplotypes and Denisovan adaptive introgression. PMID- 26883866 TI - Blood group antigen loci demonstrate multivariate genetic associations with circulating cellular adhesion protein levels in the Multi-Ethnic Study of Atherosclerosis. AB - The cellular adhesion pathway is critical in the pathophysiology of atherosclerosis, and genetic factors contributing to regulation of circulating levels of related proteins may be relevant to risk prediction of cardiovascular disease. In contrast to conducting separate genome-wide protein quantitative trait loci (pQTL) mapping analyses of each individual protein, joint genetic association analyses of multiple quantitative traits can leverage cross-trait co variation and identify simultaneous regulatory effects on protein levels across the pathway. We conducted a multi-pQTL (mpQTL) analysis of 15 proteins related to cellular adhesion assayed on 2313 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We applied the MQFAM multivariate association analysis method in PLINK on normalized protein level residuals derived from univariate linear regression, adjusting for age, sex, and principal components of ancestry. Race/ethnicity-stratified analyses identified nine genome-wide significant (P < 5e-08) loci associated with co-variation of protein levels. Although the majority of these SNPs were in proximity to structural genes of the assayed proteins, we discovered multiple loci demonstrating co-association with the circulation of at least two proteins. Of these, two significant loci specific to non-Hispanic white participants, rs17074898 at ALOX5AP (P = 1.78E-08) and rs7521237 at KIAA1614 (P = 2.2E-08), would not have met statistical significance using univariate analyses. Moreover, common patterns of multi-protein associations were discovered at the ABO locus across race/ethnicity. These results indicate the biological relevance of blood group antigens on regulation of circulating cellular adhesion pathway proteins while also demonstrating race/ethnicity-specific co-regulatory effects. PMID- 26883867 TI - New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach. AB - Platelet reactivity (PR) is variable between individuals and modulates clinical outcome in cardiovascular (CV) patients treated with antiplatelet drugs. Although several data point to a genetic control of platelet reactivity, the genes contributing to the modulation of this phenotype are not clearly identified. Integration of data derived from high-throughput technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study is to identify candidate genes modulating platelet reactivity in aspirin-treated CV patients using an integrative network-based approach. Patients with extreme high (n = 6) or low PR (n = 6) were selected and data derived from quantitative proteomic of platelets and platelet sub-cellular fractions, as well as from transcriptomic analysis were integrated with a network biology approach. Two modules within the network containing 123 and 182 genes were identified. We then specifically assessed the level of miRNAs in these two groups of patients. Among the 12 miRNAs differentially expressed, 2 (miR-135a-5p and miR-204-5p) correlated with PR. The predicted targets of these miRNAs were mapped onto the network, allowing the identification of seven overlapping genes (THBS1, CDC42, CORO1C, SPTBN1, TPM3, GTPBP2, and MAPRE2), suggesting a synergistic effect of these two miRNAs on these predicted targets. Integration of several omics data sets allowed the identification of 2 candidate miRNAs and 7 candidate genes regulating platelet reactivity in aspirin-treated CV patients. PMID- 26883868 TI - Uveo-scleral outflow pathways after ultrasonic cyclocoagulation in refractory glaucoma: an anterior segment optical coherence tomography and in vivo confocal study. AB - AIMS: To evaluate, using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM), the uveo-scleral aqueous humour (AH) outflow pathways after ultrasonic circular cyclocoagulation (UCCC). METHODS: Forty-four patients with refractory glaucoma underwent 4 or 6 s UCCC (group 1, 24 eyes; group 2, 20 eyes). UCCC was successful when the preoperative intraocular pressure (IOP) reduced by one-third. AS-OCT and IVCM were performed at baseline and at month 1 to evaluate the sclera and conjunctiva. The main outcomes were mean intra-scleral hyporeflective spaces area (MIHSA: mm2) at AS-OCT, mean density and area of conjunctival microcysts (MMD: cysts/mm2; MMA: um2) at IVCM. The relations between MIHSA, MMA and MMD with IOP were analysed. RESULTS: Mean baseline IOP was 26.9+/-2.8 mm Hg in group 1 and 27.5+/-4.0 in group 2. Intra scleral hyporeflective spaces and microcysts were observed in both groups, without significant differences in MIHSA, MMA and MMD. At month 1, UCCC was successful in 63.6% of patients (41.6% in group 1, 80% in group 2), and IOP reduced to 18.8+/-3.2 (30.1%) and 17.1+/-2.7 mm Hg (38.7%), respectively (p<0.001). MIHSA showed a twofold and threefold increase in group 1 and 2 (p<0.05), with a significant difference between groups (p<0.05). MMA and MMD increased in both groups (p<0.05), with values higher in group 2 (p<0.05). Significant relations were found between MIHSA and IOP in both groups (p<0.01). CONCLUSIONS: UCCC induced anatomical modifications of sclera and conjunctiva, which suggested that the trans-scleral AH outflow enhancement is one of the possible mechanisms exploited by ultrasounds to reduce IOP. PMID- 26883869 TI - Socioeconomic Differences in Parenting Strategies to Prevent Adolescent Smoking: A Case Study from the Netherlands. AB - PURPOSE: This study aimed to identify possible socioeconomic differences in the use of anti-smoking parenting strategies. METHODS: In 2012, survey data of adolescents (N = 225) aged 13 to 17 years and their mothers (N = 122) and fathers (N = 105) were collected in Haarlem, the Netherlands. Questions on smoking behaviour and eleven anti-smoking parenting strategies were answered by adolescents, mothers and fathers. School tracks of adolescents and educational level of parents were measured as indicators of socioeconomic position. Linear multilevel regression analyses were applied to study the association between socioeconomic position (SEP) and standardised scores of anti-smoking strategies. Analyses were controlled for age, sex and smoking by parents and adolescents. RESULTS: We found no consistent socioeconomic differences in the use of anti smoking parenting strategies. There were no statistically significant differences in relation to parental educational level or when using adolescent reports on parenting practices. However, when using parental reports, a few strategies varied significantly according to adolescent educational track. Adolescents in higher educational tracks were more likely to have no-smoking rules in the home (standardised regression coefficient (beta) = 0.20, 95 % confidence interval (CI): 0.03; 0.37, p = 0.022) and more likely to have a no-smoking agreement (beta = 0.17, 95 % CI: 0.00; 0.34, p = 0.048). However, they were less likely to frequently communicate about smoking with their parents (beta = -0.25, 95 % CI: 0.41; -0.08, p = 0.004). CONCLUSION: In this specific population, there was no consistent support for the hypothesis that anti-smoking parenting strategies contribute to socioeconomic inequalities in adolescent smoking. Parental factors that are more likely to contribute to these inequalities include parental smoking and parenting styles. PMID- 26883870 TI - Acai (Euterpe oleracea Mart.) pulp dietary intake improves cellular antioxidant enzymes and biomarkers of serum in healthy women. AB - OBJECTIVES: The aim of the present study was to evaluate the effect of acai pulp (Euterpe oleracea Martius) intake on the prevention of oxidative damage by measuring the activity of antioxidant enzymes and biomarkers of protein oxidation in women. METHODS: A nutritional intervention study was conducted with thirty five healthy women who were asked to consume 200 g/d of acai pulp for 4 wk. Blood samples were collected, and blood pressure and anthropometric parameters were measured before and after the experimental period. Antioxidant enzymes, superoxide dismutase, catalase, glutathione, production of reactive oxygen species, and total antioxidant capacity were evaluated in polymorphonuclear cells. Serum concentration of protein carbonyl and sulfhydryl groups were also determined. RESULTS: The acai intake increased catalase activity, total antioxidant capacity, and reduced the production of reactive oxygen species. Furthermore, it reduced serum concentration of protein carbonyl and increased total serum sulfhydryl groups. CONCLUSIONS: These results show the antioxidant benefit of dietary acai for the healthy women included in the present study, and may increase understanding of the beneficial health properties of this fruit. PMID- 26883871 TI - Correction to "Divergent Reactivity of Amino Acid Alkyl Ester Hydrochlorides with 2-Oxoaldehydes: Role of Selenium Dioxide To Promote Regioselective Synthesis of Imidazoles". PMID- 26883872 TI - 3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma. AB - : Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions. BIOLOGICAL SIGNIFICANCE: The current work addresses a number of challenges in 3-D MALDI IMS, driven by the small size of the mouse optic nerve and the need to maintain consistency across multiple 2-D IMS experiments. The 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions, which could then be targeted for identification and related back to the biology observed in gliomas of the optic nerve. PMID- 26883873 TI - Integrative characterization of the venom of the coral snake Micrurus dumerilii (Elapidae) from Colombia: Proteome, toxicity, and cross-neutralization by antivenom. AB - In Colombia, nearly 2.8% of the 4200 snakebite accidents recorded annually are inflicted by coral snakes (genus Micrurus). Micrurus dumerilii has a broad distribution in this country, especially in densely populated areas. The proteomic profile of its venom was here studied by a bottom-up approach combining RP-HPLC, SDS-PAGE and MALDI-TOF/TOF. Venom proteins were assigned to eleven families, the most abundant being phospholipases A2 (PLA2; 52.0%) and three finger toxins (3FTx; 28.1%). This compositional profile shows that M. dumerilii venom belongs to the 'PLA2-rich' phenotype, in the recently proposed dichotomy for Micrurus venoms. Enzymatic and toxic venom activities correlated with protein family abundances. Whole venom induced a conspicuous myotoxic, cytotoxic and anticoagulant effect, and was mildly edematogenic and proteolytic, whereas it lacked hemorrhagic activity. Some 3FTxs and PLA2s reproduced the lethal effect of venom. A coral snake antivenom to Micrurus nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect. The combined compositional, functional, and immunological data here reported for M. dumerilii venom may contribute to a better understanding of these envenomings, and support the possible use of anti M. nigrocinctus coral snake antivenom in their treatment. BIOLOGICAL SIGNIFICANCE: Coral snakes represent a highly diversified group of elapids in the New World, with nearly 70 species within the genus Micrurus. Owing to their scarce yields, the biochemical composition and toxic activities of coral snake venoms have been less well characterized than those of viperid species. In this work, an integrative view of the venom of M. dumerilii, a medically relevant coral snake from Colombia, was obtained by a combined proteomic, functional, and immunological approach. The venom contains proteins from at least eleven families, with a predominance of phospholipases A2 (PLA2), followed by three finger toxins (3FTx). According to its compositional profile, M. dumerilii venom can be grouped with those of several Micrurus species from North and Central America that present a PLA2-predominant phenotype, to date it is the most southerly coral snake species to do so. Other coral snake species that a 'PLA2 rich' venom, M. dumerilii venom contains both components that form MitTx, a pain inducing heterodimeric complex recently characterized from the venom of Micrurus tener, also present in Micrurus mosquitensis and M. nigrocinctus venoms. In addition to a lethal three-finger toxin, PLA2s participate in the toxicity of M. dumerilii venom, some of them displaying ability to induce cytolysis, muscle necrosis, and lethality to mice. An antivenom to M. nigrocinctus demonstrated significant cross-recognition of M. dumerilii venom proteins, and accordingly, ability to neutralize its lethal effect, being of potential therapeutic usefulness in these envenomings. PMID- 26883874 TI - Concentration, population, and context-dependent effects of AM251 in zebrafish. AB - RATIONALE: The function of the cannabinoid type 1 receptor (CB1-R) is poorly understood in zebrafish, and numerous inconsistent effects have been reported on it in the literature. OBJECTIVE: The objective of the present study is to determine whether differences in the reported effects of CB1-R antagonism on anxiety-like behavioural responses, dopaminergic and serotonergic responses are due to concentration, context-dependent and/or population (genotype-related) effects. METHOD: Two genetically distinct populations of zebrafish (AB and short fin (SF)) were treated with different concentrations of AM251 (0, 0.1, 1mg/L), and behavioural responses were quantified under two different contexts: one, following habituation and two, subsequently in a novel environment. The levels of dopamine, serotonin and their metabolites 3,4-dihydroxyindole acetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were quantified from whole-brain tissue. RESULTS: We demonstrate that a 60-min exposure to AM251 (0, 0.1, 1mg/L) does not alter behavioural performance following habituation in either populations. However, when subsequently transferred to a novel environment, zebrafish that were pre-treated with the highest dose of AM251 (1mg/L) exhibited increased anxiety-like behavioural responses including elevated absolute turn angle, freezing and bottom dwelling. We found that exposure to the highest dose of AM251 (1mg/L) for 60min increased serotonin in fish of both populations tested. In contrast, exposure to 0.1mg/L AM251 decreased, whereas to 1mg/L AM251 increased dopamine, DOPAC and 5-HIAA in fish of both populations. CONCLUSION: Our results demonstrate a genotype-independent effect of AM251 but imply that the inconsistent findings obtained after pharmacological blockade of CB1-Rs in zebrafish may be due to a combination of concentration- and environmental context dependent effects. PMID- 26883875 TI - 17alpha-ethinyl estradiol attenuates depressive-like behavior through GABAA receptor activation/nitrergic pathway blockade in ovariectomized mice. AB - OBJECTIVES: This study was performed to investigate the antidepressant-like effect of 17alpha-ethinyl estradiol (EE2) in ovariectomized (OVX) mice and the possible role of nitrergic and gamma aminobutyric acid (GABA)ergic pathways in this paradigm. METHODS: Bilateral ovariectomy was performed in female mice, and different doses of EE2 were intraperitoneally injected either alone or combined with GABAA agonist, diazepam, GABAA antagonist, flumazenil, non-specific nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), specific nNOS inhibitor, 7-nitroindazole (7-NI), a nitric oxide (NO) precursor, L arginine, and selective PDE5I, sildenafil. After locomotion assessment, immobility times were recorded in the forced swimming test (FST) and tail suspension test (TST). Moreover, hippocampal nitrite concentrations were measured in the examined groups. RESULTS: Ten days after ovariectomy, a significant prolonged immobility times were observed. EE2 (0.3 and 1MUg/kg and 0.03, 0.1, and 1mg/kg) caused antidepressant-like activity in OVX mice in FST and TST. Diazepam (1 and 5mg/kg), L-NAME (30mg/kg), and 7-NI (100mg/kg) significantly reduced the immobility times. Co-administration of minimal and sub-effective doses of EE2 and diazepam (0.3MUg/kg and 0.5mg/kg, respectively) exerted a significant antidepressant-like effect. The same effect was observed in combination of minimal and sub-effective doses of EE2 and either L-NAME or 7-NI. Moreover, combination of minimal and sub-effective doses of EE2, diazepam either L-NAME, or 7-NI emphasized the significant robust antidepressant-like activity. CONCLUSIONS: The study has demonstrated that lowest dose of EE2 exerts a significant antidepressant-like behavior. It is suggested that suppression of NO system, as well as GABAA activation, may be responsible for antidepressant-like activity of EE2 in OVX mice. Moreover, GABAA activation may inhibit nitrergic pathway. PMID- 26883876 TI - Enhancement of tumor cell susceptibility to natural killer cell activity through inhibition of the PI3K signaling pathway. AB - Natural killer (NK) cells are the primary effectors of the innate immune response against virus-infected cells or cells that have undergone malignant transformation. NK cells recognize their targets through a complex array of activating and inhibitory receptors, which regulate the intensity of the effector response against individual target cells. However, many studies have shown that tumor cells can escape immune cell recognition through a variety of mechanisms, developing resistance to NK cell killing. Using a lentiviral shRNA library, we previously demonstrated that several common signaling pathways modulate susceptibility of tumor cells to NK cell activity. In this study, we focused on one of the genes (PI3KCB), identified in this genetic screen. The PI3KCB gene encodes an isoform of the catalytic subunit of PI3K called P110beta. The PI3K pathway has been linked to diverse cellular functions, but has never been associated with susceptibility to NK cell activity. Gene silencing of PI3KCB resulted in increased susceptibility of several tumor cell lines to NK cell lytic activity and induced increased IFN-gamma secretion by NK cells. Treatment of primary tumor cells with two different PI3K inhibitors also increased target cell susceptibility to NK cell activity. These effects are due, at least in part, to modulation of several activating and inhibitory ligands and appear to be correlated with PI3K signaling pathway inhibition. These findings identify a new and important role of PI3KCB in modulating tumor cell susceptibility to NK cells and open the way to future combined target immunotherapies. PMID- 26883877 TI - Analysis of ISO/IEEE 11073 built-in security and its potential IHE-based extensibility. AB - The ISO/IEEE 11073 standard for Personal Health Devices (X73PHD) aims to ensure interoperability between Personal Health Devices and aggregators-e.g. health appliances, routers-in ambulatory setups. The Integrating the Healthcare Enterprise (IHE) initiative promotes the coordinated use of different standards in healthcare systems (e.g. Personal/Electronic Health Records, alert managers, Clinical Decision Support Systems) by defining profiles intended for medical use cases. X73PHD provides a robust syntactic model and a comprehensive terminology, but it places limited emphasis on security and on interoperability with IHE compliant systems and frameworks. However, the implementation of eHealth/mHealth applications in environments such as health and fitness monitoring, independent living and disease management (i.e. the X73PHD domains) increasingly requires features such as secure connections to mobile aggregators-e.g. smartphones, tablets-, the sharing of devices among different users with privacy, and interoperability with certain IHE-compliant healthcare systems. This work proposes a comprehensive IHE-based X73PHD extension consisting of additive layers adapted to different eHealth/mHealth applications, after having analyzed the features of X73PHD (especially its built-in security), IHE profiles related with these applications and other research works. Both the new features proposed for each layer and the procedures to support them have been carefully chosen to minimize the impact on X73PHD, on its architecture (in terms of delays and overhead) and on its framework. Such implications are thoroughly analyzed in this paper. As a result, an extended model of X73PHD is proposed, preserving its essential features while extending them with added value. PMID- 26883878 TI - Erratum to: Impact of New Genomic Technologies on Understanding Adverse Drug Reactions. PMID- 26883879 TI - Pharmacokinetics of Cannabis in Cancer Cachexia-Anorexia Syndrome. AB - Anorexia can affect up to 90 % of people with advanced cancer. It is a complex symptom associated with changes in taste, lack of hunger at mealtimes and lack of food enjoyment. Associated weight loss is part of the physical decline that occurs as cancer worsens. Weight loss can also occur from cachexia, the increased metabolism of energy due to raised inflammatory cytokines, liver metastases and other factors seen in several advanced cancers. Independent of anorexia, although frequently associated (where it is referred to as the cachexia-anorexia syndrome), it accounts for a significant amount of morbidity and deaths in people with cancer. In particular, quality of life for the patient and the family is significantly affected with this syndrome as it causes anxiety and distress. Therefore, it is important that research into therapies is undertaken, particularly focusing on an understanding of the pharmacokinetic properties of compounds in this cachexic population. Cannabinoids are one such group of therapies that have received a large amount of media focus recently. However, there appears to be a lack on rigorous pharmacokinetic data of these complex and varied compounds in the cachexic population. Similarly, there is a lack of pharmacokinetic data in any population group for the non- tetrahydrocannabinol (THC) and cannabidiol (CBD) cannabinoids (often due to the lack of analytical standards for quantification). This review will thus examine the pharmacokinetics of major cannabinoids i.e. THC and CBD in a cancer population. Overall, based on the current literature, evidence for the use of cannabinoids for the treatment of cancer-related cachexia-anorexia syndrome remains equivocal. A high-quality, rigorous, phase I/II study to elicit pharmacokinetic dose-concentration and concentration-response data, with a clinically acceptable mode of delivery to reduce intrapatient variability and enable more consistent bioavailability is needed in this population. PMID- 26883880 TI - Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis. AB - CONTEXT: The impact of dietary protein on body composition changes after older adults purposefully lose weight requires systematic evaluation OBJECTIVE: : This systematic review and meta-analysis assessed the effects of protein intake (< 25% vs >= 25% of energy intake or 1.0 g/kg/d) on energy restriction-induced changes in body mass, lean mass, and fat mass in adults older than 50 years. DATA SOURCES: PubMed, Cochrane, Scopus, and Google Scholar were searched using the keywords "dietary proteins," "body composition," "skeletal muscle," and "muscle strength." STUDY SELECTION: Two researchers independently screened 1542 abstracts. DATA EXTRACTION: Information was extracted from 24 articles. DATA SYNTHESIS: Twenty randomized control trials met the inclusion criteria. CONCLUSION: Older adults retained more lean mass and lost more fat mass during weight loss when consuming higher protein diets. PMID- 26883883 TI - One-way helical electromagnetic wave propagation supported by magnetized plasma. AB - In this paper we reveal the presence of photonic one-way helical surface states in a simple natural system- magnetized plasma. The application of an external magnetic field to a bulk plasma body not only breaks time-reversal-symmetry but also leads to separation of Equi-Frequency Contour surfaces (EFCs) to form topologically nontrivial gaps in k space. Interestingly, these EFCs support topologically protected surface states. We numerically investigate an interface between magnetized plasma, using a realistic model for parameter dispersion, and vacuum, to confirm the existence of one-way scatter-immune helical surface states. Unlike previous proposals for achieving photonic one-way propagation, our scheme does not require the use of artificial structures and should therefore be simple to implement experimentally. PMID- 26883881 TI - Role of maternal vitamins in programming health and chronic disease. AB - Vitamin consumption prior to and during pregnancy has increased as a result of proactive recommendations by health professionals, wide availability of vitamin supplements, and liberal food-fortification policies. Folic acid, alone or in combination with other B vitamins, is the most recommended vitamin consumed during pregnancy because deficiency of this vitamin leads to birth defects in the infant. Folic acid and other B vitamins are also integral components of biochemical processes that are essential to the development of regulatory systems that control the ability of the offspring to adapt to the external environment. Although few human studies have investigated the lasting effects of high vitamin intakes during pregnancy, animal models have shown that excess vitamin supplementation during gestation is associated with negative metabolic effects in both the mothers and their offspring. This research from animal models, combined with the recognition that epigenetic regulation of gene expression is plastic, provides evidence for further examination of these relationships in the later life of pregnant women and their children. PMID- 26883884 TI - Using the general-purpose reactivity indicator: challenging examples. AB - We elucidate the regioselectivity of nucleophilic attack on substituted benzenesulfonates, quinolines, and pyridines using a general-purpose reactivity indicator (GPRI) for electrophiles. We observe that the GPRI is most accurate when the incoming nucleophile resembles a point charge. We further observe that the GPRI often chooses reactive "dead ends" as the most reactive sites as well as sterically hindered reactive sites. This means that care must be taken to remove sites that are inherently unreactive. Generally, among sites where reactions actually occur, the GPRI identifies the sites in the molecule that lead to the kinetically favored product(s). Furthermore, the GPRI can discern which sites react with hard reagents and which sites react with soft reagents. Because it is currently impossible to use the mathematical framework of conceptual DFT to identify sterically inaccessible sites and reactive dead ends, the GPRI is primarily useful as an interpretative, not a predictive, tool. PMID- 26883885 TI - Quantification of platelets and platelet derived growth factors from platelet rich-plasma (PRP) prepared at different centrifugal force (g) and time. AB - INTRODUCTION: Platelet derived biomaterials represent a key source of cytokines and growth factors extensively used for tissue regeneration; wound healing and tissue repair. Our study was to quantify platelets and growth factors released by PRP when prepared at different centrifugal force (g) and time. MATERIAL AND METHODS: Our study was approved by the institutional ethical committee. One hundred millilitres of whole blood (WB) was collected in bag with CPDA as the anticoagulant(AC); (14 mL for 100 mL WB ratio). Nine aliquots of 10 mL each were made from the bag and set of three aliquots were made a group. PRP was prepared at varying centrifugal force (group A: -110 g, group B: -208 g & group C: -440 g) & time (1: -5 min, 2: -10 min & 3: -20 min). Contents of each PRP prepared were analysed. Commercial sandwich ELISA kits were used to quantify the concentrations of CD62P (Diaclone SAS; France), Platelet derived growth factors-AB (Qayee-Bio; China), transforming growth factor-beta1 (DRG; Germany) and vascular endothelial growth factor (Boster Immuno Leader; USA) released in each PRP prepared. RESULTS: Eight volunteers were enrolled in the study (24-30 years). The baseline blood counts of all the volunteers were comparable (p >= 0.05). Mean +/- SD of platelet yield of all nine groups ranged from 17.2 +/- 4.2% to 78.7 +/- 5.7%. Each PRP was activated with calcified thromboplastin to quantify the growth factors released by them. Significantly higher (p < 0.05) transforming growth factor-beta1 and vascular endothelial growth factor were released compared to the baseline. CONCLUSION: Our study highlights the variation in both force (g) and time results in changes at cellular level and growth factor concentrations. PMID- 26883882 TI - Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota. AB - The epidemic of metabolic diseases has raised questions about the interplay between the human diet and the gut and its microbiota. The gut has two vital roles: nutrient absorption and intestinal barrier function. Gut barrier defects are involved in many diseases. Excess energy intake disturbs the gut microbiota and favors body entry of microbial compounds that stimulate chronic metabolic inflammation. In this context, the natural defense mechanisms of gut epithelial cells and the potential to boost them nutritionally warrant further study. One such important defense system is the activation of inducible heat-shock proteins (iHSPs) which protect the gut epithelium against oxidative stress and inflammation. Importantly, various microbial components can induce the expression of iHSPs. This review examines gut epithelial iHSPs as the main targets of microbial signals and nutrients and presents data on diseases involving disturbances of gut epithelial iHSPs. In addition, a broad literature analysis of dietary modulation of gut epithelial iHSPs is provided. Future research aims should include the identification of gut microbes that can optimize gut protective iHSPs and the evaluation of iHSP-mediated health benefits of nutrients and food components. PMID- 26883888 TI - Physicians don't follow guidelines: What are we to do? PMID- 26883886 TI - Age, Dehydration, Respiratory Failure, Orientation Disturbance, and Blood Pressure Score Predicts In-hospital Mortality in HIV-negative Non-multidrug resistant Smear-positive Pulmonary Tuberculosis in Japan. AB - The A-DROP scoring system was originally designed to assess clinical severity of community acquired pneumonia using the following parameters: advanced Age, Dehydration, Respiratory failure, Orientation disturbance (confusion); and, low blood Pressure. Total A-DROP score ranges zero to five assigning one point for each component, wherein five indicates the poorest prognosis. The purpose of this single-center retrospective study was to determine whether A-DROP could predict the risk for death in patients with pulmonary tuberculosis. We reviewed consecutive HIV-negative, non-multidrug-resistant smear-positive adult pulmonary tuberculosis patients. The cohort consisted of 134 men (38.8%), 211 women (61.2%), 272 who discharged alive (28.8%), and 73 who died in-hospital (21.2%) with a median age of 72 (IQR: 54-82) years. A one-point increase in the A-DROP score was associated with a higher risk for in-hospital mortality with odds ratio of 3.8 (95% confidence interval 2.8-5.2, P < 0.001). The area under receiver operating characteristics curve was 0.86. The total score cutoff of 1.5 provided the best Youden Index of 0.61. Using this criteria, total score >1.5, sensitivity was 85% and specificity was 76%. Kaplan-Meier curve clearly indicated that in hospital mortality increased with higher A-DROP scores (Log-rank test <0.001). In conclusion, A-DROP score clearly indicate pulmonary tuberculosis in-hospital mortality. PMID- 26883889 TI - Aspergillosis spores and medical marijuana. PMID- 26883890 TI - Psychedelic and nonpsychedelic LSD and psilocybin for cluster headache. PMID- 26883891 TI - Hexadecameric structure of an invertebrate gap junction channel. AB - Innexins are invertebrate-specific gap junction proteins with four transmembrane helices. These proteins oligomerize to constitute intercellular channels that allow for the passage of small signaling molecules associated with neural and muscular electrical activity. In contrast to the large number of structural and functional studies of connexin gap junction channels, few structural studies of recombinant innexin channels are reported. Here we show the three-dimensional structure of two-dimensionally crystallized Caenorhabditis elegans innexin-6 (INX 6) gap junction channels. The N-terminal deleted INX-6 proteins are crystallized in lipid bilayers. The three-dimensional reconstruction determined by cryo electron crystallography reveals that a single INX-6 gap junction channel comprises 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which comprise 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26. Two bulb densities are observed in each hemichannel, one in the pore and the other at the cytoplasmic side of the hemichannel in the channel pore pathway. These findings imply a structural diversity of gap junction channels among multicellular organisms. PMID- 26883892 TI - Combined Use of Mesenchymal Stromal Cell Sheet Transplantation and Local Injection of SDF-1 for Bone Repair in a Rat Nonunion Model. AB - Bone nonunion treatments pose a challenge in orthopedics. This study investigated the joint effects of using mesenchymal stem cell (MSC) sheets with local injection of stromal cell-derived factor-1 (SDF-1) on bone formation. In vitro, we found that migration of MSCs was mediated by SDF-1 in a dose-dependent manner. Moreover, stimulation with SDF-1 had no direct effect on the proliferation or osteogenic differentiation of MSCs. Furthermore, the results indicated elevated expression levels of bone morphogenetic protein 2, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor in MSC sheets compared with MSCs cultured in medium. New bone formation in fractures was evaluated by X-ray, micro-computed tomography (micro-CT), hematoxylin and eosin (H&E) staining, Safranin-O staining, and immunohistochemistry in vivo. In the rat bone fracture model, the MSC sheets transplanted into the injured site along with injection of SDF-1 showed significantly more new bone formation within the gap. Moreover, at 8 weeks, complete bone union was obtained in this group. In contrast, the control group showed nonunion of the bone. Our study suggests a new strategy involving the use of MSC sheets with a local injection of SDF-1 for hard tissue reconstruction, such as the healing of nonunions and bone defects. PMID- 26883893 TI - Tunable short-wavelength spin wave excitation from pinned magnetic domain walls. AB - Miniaturization of magnonic devices for wave-like computing requires emission of short-wavelength spin waves, a key feature that cannot be achieved with microwave antennas. In this paper, we propose a tunable source of short-wavelength spin waves based on highly localized and strongly pinned magnetic domain walls in ferroelectric-ferromagnetic bilayers. When driven into oscillation by a microwave spin-polarized current, the magnetic domain walls emit spin waves with the same frequency as the excitation current. The amplitude of the emitted spin waves and the range of attainable excitation frequencies depend on the availability of domain wall resonance modes. In this respect, pinned domain walls in magnetic nanowires are particularly attractive. In this geometry, spin wave confinement perpendicular to the nanowire axis produces a multitude of domain wall resonances enabling efficient spin wave emission at frequencies up to 100 GHz and wavelengths down to 20 nm. At high frequency, the emission of spin waves in magnetic nanowires becomes monochromatic. Moreover, pinning of magnetic domain wall oscillators onto the same ferroelectric domain boundary in parallel nanowires guarantees good coherency between spin wave sources, which opens perspectives towards the realization of Mach-Zehnder type logic devices and sensors. PMID- 26883895 TI - Coexistence of multiple metastable polytypes in rhombohedral bismuth. AB - Derivative structural polytypes coexisting with the rhombohedral A7 structure of elemental bismuth (Bi) have been discovered at ambient condition, based on microstructure analyses of pure Bi samples treated under high pressure and high temperature conditions. Three structures with atomic positions close to those of the A7 structure have been identified through first-principles calculations, showing these polytypes energetically comparable to the A7 structure under ambient condition. Simulated diffraction data are in excellent agreement with the experimental observations. We argue that previously reported some variations of physical properties (e.g., density, electrical conductivity, and magnetism) in bismuth could be due to the formation of these polytypes. The coexistence of metastable derivative structural polytypes may be a widely occurring phenomenon in other elemental materials. PMID- 26883896 TI - Copper-catalyzed borylative coupling of vinylazaarenes and N-Boc imines. AB - Cu-catalyzed three-component couplings of vinylazaarenes, B2(pin)2, and N-Boc imines are described. Oxidation of the initially formed boronate gives azaarene containing, Boc-protected amino alcohols with reasonable to good diastereoselectivities. PMID- 26883894 TI - ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs. AB - Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID- 26883897 TI - Sunlight-Triggered Nanoparticle Synergy: Teamwork of Reactive Oxygen Species and Nitric Oxide Released from Mesoporous Organosilica with Advanced Antibacterial Activity. AB - Colonization of surfaces by microorganisms is an urging problem. In combination with the increasing antibiotic resistance of pathogenic bacteria, severe infections are reported more frequently in medical settings. Therefore, there is a large demand to explore innovative surface coatings that provide intrinsic and highly effective antibacterial activity. Materials containing silver nanoparticles have been developed in the past for this purpose, but this solution has come into criticism due to various disadvantages like notable toxicity against higher organisms, the high price, and low abundance of silver. Here, we introduce a new, sunlight-mediated organosilica nanoparticle (NP) system based on silver-free antibacterial activity. The simultaneous release of nitric oxide (NO) in combination with singlet oxygen and superoxide radicals (O2(*-)) as reactive oxygen species (ROS) leads to the emergence of highly reactive peroxynitrite molecules with significantly enhanced biocidal activity. This special cooperative effect can only be realized, if the ROS-producing moieties and the functional entities releasing NO are spatially separated from each other. In one type of particle, Rose Bengal as an efficient singlet oxygen ((1)O2) producer was covalently bound to SH functionalities applying thiol-ene click chemistry. "Charging" the second type of particles with NO was realized by quantitatively transferring the thiol groups into S-nitrosothiol functionalities. We probed the oxidation power of ROS-NP alone and in combination with NO-NP using sunlight as a trigger. The high antibacterial efficiency of dual-action nanoparticles was demonstrated using disinfection assays with the pathogenic bacterium Pseudomonas aeruginosa. PMID- 26883898 TI - LV mechanical dispersion as a predictor of ventricular arrhythmia in patients with advanced systolic heart failure : A pilot study. AB - BACKGROUND: Myocardial mechanical dyssynchrony induced by the presence of postinfarction scar and/or conduction abnormalities in patients with a left ventricular ejection fraction (LVEF) of < 35 % may be associated with a greater propensity toward inducing serious ventricular arrhythmia [(ventricular tachycardia (VT), ventricular fibrillation (VF)] and sudden cardiac death. The assessment of regional myocardial function using tissue Doppler echocardiography (TDE) allows for noninvasive analysis of regional mechanical dysfunction (LV mechanical dispersion). AIM: The aim of this study was to evaluate the TDE-based mechanical dispersion as a potential echocardiographic predictor of VT/VF. METHODS: The study group consisted of 47 consecutive ambulatory patients with implanted cardiac resynchronization therapy-defibrillator (CRT-D) devices who were divided into two groups: Group 1 (n = 29) comprised patients with recorded episodes of VT/VF, in whom baseline TDE data were available, and group 2 (n = 18) comprised patients without registered VT/VF in the device memory within 4 years after implantation. LV mechanical dispersion was defined as the standard deviation of the time measured from the beginning of the QRS complex to the peak longitudinal strain in apical four-chamber and two-chamber views. A retrospective quantitative assessment of LV regional deformation was based on the color tissue velocity recordings. RESULTS: The average time to event after implantation was 345 days. Patients with electrical events demonstrated greater mechanical dispersion: 99.14 +/- 33.60 vs. 72.98 +/- 19.70, p=0.002. CONCLUSION: During the 4-year follow-up, patients with documented VT/VF were characterized by significantly higher LV mechanical dispersion as compared with patients without electrical events. Measurement of LV mechanical dispersion might be helpful in determining the risk of sudden cardiac death. PMID- 26883899 TI - Single-catheter approach to pulmonary vein reisolation in selected patients : Data from a prospective registry. AB - BACKGROUND: In addition to different types of single-tip ablation catheters for pulmonary vein (PV) reisolation, a newly developed circular mapping and ablation catheter (nMARQ(r)) has been available since 2013 and is currently used only in initial PV isolation procedures. In this prospective registry we present feasibility and efficacy data for PV reisolation procedures with a single catheter approach (nMARQ(r)) compared with a standard approach using a single-tip ablation catheter and a circular mapping catheter. METHODS: We included 35 carefully selected patients in this prospective registry and assigned them in a 2:1 ratio to undergo either PV reisolation with a single-tip ablation catheter together with a steerable circular mapping catheter (group 1) or with the nMARQ(r)catheter only (group 2). The recurrence rate was calculated for atrial tachyarrhythmias with a duration of > 30 s during a mean follow-up of 12.7 months. RESULTS: Reisolation of all PVs was achieved in all patients of both groups. In group 2, all gaps could be correctly identified with the nMARQ(r) catheter. PV isolation was clearly visible on the nMARQ(r) catheter in all targeted veins. With the nMARQ(r) catheter the ablation time decreased significantly (6.3 +/- 3.0 vs. 18.6 +/- 13.9 min, p < 0.05). The recurrence rate of atrial fibrillation did not differ significantly between the two groups (37.5 vs. 45.5 %, p = 0.66). CONCLUSION: In selected patients, a complete PV reisolation procedure is feasible with a singular circular mapping and ablation catheter. The 12-months success rate is comparable to a classic approach with a combination of a single-tip ablation catheter and a circular mapping catheter. PMID- 26883900 TI - [Impact of guideline adherence on mortality in treatment of left heart failure]. AB - BACKGROUND: The German national guidelines on chronic heart failure provide treatment recommendations to physicians and reflect the current level of evidence; however, it is questionable to what extent these recommendations are applied in the routine practice and what the effect of guideline adherence on mortality is. METHODS: In this study the claims data of a major German health insurance fund collected over a period of 4 years were analyzed. Using binary logistic regression and Cox regression analyses the influence of drug prescriptions, diagnostic measures, influenza vaccination, the New York Heart Association (NYHA) status, the age and gender on mortality were examined. RESULTS: The study population consisted of 85,465 heart failure patients. Approximately 60 % of the drugs were prescribed according to the guidelines. There was a positive correlation between a higher NYHA status and mortality with an odds ratio (OR) of 3.264. Especially pharmacotherapy with angiotensin converting enzyme (ACE) inhibitors and beta blockers according to the guidelines was associated with a lower mortality rate (OR 0.448 resp. 0.444). Also patients diagnosed using echocardiography at regular intervals showed a lower risk of dying (OR 0.314). CONCLUSION: The results of this large sample could confirm the results of clinical trials that a therapy according to the guidelines has a significant impact on mortality. By analyzing the claims data evidence was found that in the treatment of heart failure patients the medical results could be improved by adherence to guideline recommendations. PMID- 26883901 TI - A genome-wide association study identifies a genomic region for the polycerate phenotype in sheep (Ovis aries). AB - Horns are a cranial appendage found exclusively in Bovidae, and play important roles in accessing resources and mates. In sheep (Ovies aries), horns vary from polled to six-horned, and human have been selecting polled animals in farming and breeding. Here, we conducted a genome-wide association study on 24 two-horned versus 22 four-horned phenotypes in a native Chinese breed of Sishui Fur sheep. Together with linkage disequilibrium (LD) analyses and haplotype-based association tests, we identified a genomic region comprising 132.0-133.1 Mb on chromosome 2 that contained the top 10 SNPs (including 4 significant SNPs) and 5 most significant haplotypes associated with the polycerate phenotype. In humans and mice, this genomic region contains the HOXD gene cluster and adjacent functional genes EVX2 and KIAA1715, which have a close association with the formation of limbs and genital buds. Our results provide new insights into the genetic basis underlying variable numbers of horns and represent a new resource for use in sheep genetics and breeding. PMID- 26883902 TI - A four-coordinate cobalt(II) single-ion magnet with coercivity and a very high energy barrier. AB - Single-molecule magnets display magnetic bistability of molecular origin, which may one day be exploited in magnetic data storage devices. Recently it was realised that increasing the magnetic moment of polynuclear molecules does not automatically lead to a substantial increase in magnetic bistability. Attention has thus increasingly focussed on ions with large magnetic anisotropies, especially lanthanides. In spite of large effective energy barriers towards relaxation of the magnetic moment, this has so far not led to a big increase in magnetic bistability. Here we present a comprehensive study of a mononuclear, tetrahedrally coordinated cobalt(II) single-molecule magnet, which has a very high effective energy barrier and displays pronounced magnetic bistability. The combined experimental-theoretical approach enables an in-depth understanding of the origin of these favourable properties, which are shown to arise from a strong ligand field in combination with axial distortion. Our findings allow formulation of clear design principles for improved materials. PMID- 26883904 TI - Stress alters asenapine-induced Fos expression in the Meynert's nucleus: response of adjacent hypocretin and melanin-concentrating hormone neurons in rat. AB - OBJECTIVE: Asenapine (ASE), an atypical antipsychotic drug used in the treatment of schizophrenia, induces Fos expression in forebrain. Effect of ASE on activity of basal nucleus of Meynert (NBM) cells, a part of the striatal-cortical circuits, was studied. We were also interested to reveal whether a chronic unpredictable variable mild stress (CMS) preconditioning might affect the ASE impact. METHODS: Rats were divided into as follows: controls-vehicle, controls ASE, stressed-vehicle and stressed-ASE groups. CMS included restrain, social isolation, crowding, swimming and cold applied for 21 days. On the 22nd day, rats were subcutaneously injected with ASE (0.3 mg/kg) or vehicle (saline 300 MUl/rat), 90 min prior euthanizing. After transcardial fixation, brains were cut into 30 MUm thick coronal sections. Fos protein presence, as indicator of cell activity, was detected by ABC immunohistochemistry. Hypocretin (Hcrt) and melanin concentrating hormone (MCH) containing cells were visualized with fluorescent dyes. RESULTS: ASE induced significant increase in Fos expression in NBM in both controls and CMS preconditioned rats in comparison with the related vehicle treated controls. CMS preconditioning, however, significantly lowered the Fos response to ASE in NBM. From Hrct and MCH cells, only Hcrt ones displayed Fos presence in response to ASE. DISCUSSION: This study demonstrates for the first time that ASE may target a special group of cells occupying NBM, which effect can be modulated by CMS preconditioning. This finding extends a view that ASE impact may extend beyond the classical forebrain target areas common for the action of all antipsychotics and might be helpful in the identification of sites and side effects of its therapeutic actions. PMID- 26883903 TI - A comprehensive review of the barriers and promoters health workers experience in delivering prevention of vertical transmission of HIV services in sub-Saharan Africa. AB - Despite significant biomedical and policy advances, 199,000 infants and young children in sub-Saharan Africa (SSA) became infected with HIV in 2013, indicating challenges to implementation of these advances. To understand the nature of these challenges, we sought to (1) characterize the barriers and facilitators that health workers encountered delivering prevention of vertical transmission of HIV (PVT) services in SSA and (2) evaluate the use of theory to guide PVT service delivery. The PubMed and CINAHL databases were searched using keywords barriers, facilitators, HIV, prevention of vertical transmission of HIV, health workers, and their synonyms to identify relevant studies. Barriers and facilitators were coded at ecological levels according to the Determinants of Performance framework. Factors in this framework were then classified as affecting motivation, opportunity, or ability, per the Motivation-Opportunity-Ability (MOA) framework in order to evaluate domains of health worker performance within each ecological level. We found that the most frequently reported challenges occurred within the health facility level and spanned all three MOA domains. Barriers reported in 30% or more of studies from most proximal to distal included those affecting health worker motivation (stress, burnout, depression), patient opportunity (stigma), work opportunity (poor referral systems), health facility opportunity (overburdened workload, lack of supplies), and health facility ability (inadequate PVT training, inconsistent breastfeeding messages). Facilitators were reported in lower frequencies than barriers and tended to be resolutions to challenges (e.g., quality supervision, consistent supplies) or responses to an intervention (e.g., record systems and infrastructure improvements). The majority of studies did not use theory to guide study design or implementation. Interventions addressing health workers' multiple ecological levels of interactions, particularly the health facility, hold promise for far reaching impact as distal factors influence more proximal factors. Incorporating theory that considers factors beyond the health worker will strengthen endeavors to mitigate barriers to PVT service delivery. PMID- 26883905 TI - Health-Related Quality of Life Trajectories over the First Year after Stroke in Colombia, South America. AB - BACKGROUND Stroke is the second most common cause of death around the world, and little is known about long-term HRQOL outcomes for Latino American individuals after stroke. OBJECTIVE The purpose of the study is to compare HRQOL trajectories in stroke survivors to a group of healthy controls from Colombia first year post stroke. METHODS Forty individuals diagnosed with stroke and 50 controls were recruited from the Psychological Attention Center of Antonio Narino University. RESULTS Hierarchical linear models suggested that trajectories of all eight indices of HRQOL were lower over time in stroke individuals compared to controls. Stroke patients showed gains in the HRQOL domains of physical functioning, role limitations - physical, role limitations - emotional, pain, and social functioning, although only pain in stroke individuals approached that of controls at 12 months. Despite these improvements, seven of the eight indices of HRQOL in stroke individuals remained very low over time, suggesting that the vast majority of rehabilitation gains in HRQOL, even when present, were extremely limited. CONCLUSIONS The current findings suggest a need in Latin America for mental health services after stroke, as well as other interventions designed to increase social and family support, which may thereby improve mental health. PMID- 26883907 TI - Histone Deacetylase-3/CAGE Axis Targets EGFR Signaling and Regulates the Response to Anti-Cancer Drugs. AB - We have previously reported the role of miR-326-HDAC3 loop in anti-cancer drug resistance. CAGE, a cancer/testis antigen, regulates the response to anti-cancer drug-resistance by forming a negative feedback loop with miR-200b. Studies investigating the relationship between CAGE and HDAC3 revealed that HDAC3 negatively regulated the expression of CAGE. ChIP assays demonstrated the binding of HDAC3 to the promoter sequences of CAGE. However, CAGE did not affect the expression of HDAC3. We also found that EGFR signaling regulated the expressions of HDAC3 and CAGE. Anti-cancer drug-resistant cancer cell lines show an increased expression of pEGFR(Y845). HDAC3 was found to negatively regulate the expression of pEGFR(Y845). CAGE showed an interaction and co-localization with EGFR. It was seen that miR-326, a negative regulator of HDAC3, regulated the expression of CAGE, pEGFR(Y845), and the interaction between CAGE and EGFR. miR-326 inhibitor induced the binding of HDAC3 to the promoter sequences in anti-cancer drug resistant Malme3M(R) cells, decreasing the tumorigenic potential of Malme3M(R) cells in a manner associated with its effect on the expression of HDAC3, CAGE and pEGFR(Y845). The down-regulation of HDAC3 enhanced the tumorigenic, angiogenic and invasion potential of the anti-cancer drug-sensitive Malme3M cells in CAGE dependent manner. Studies revealed that PKCdelta was responsible for the increased expression of pEGFR(Y845) and CAGE in Malme3M(R) cells. CAGE showed an interaction with PKCdelta in Malme3M(R) cells. Our results show that HDAC3-CAGE axis can be employed as a target for overcoming resistance to EGFR inhibitors. PMID- 26883908 TI - Structural Analysis of the Streptomyces avermitilis CYP107W1-Oligomycin A Complex and Role of the Tryptophan 178 Residue. AB - CYP107W1 from Streptomyces avermitilis is a cytochrome P450 enzyme involved in the biosynthesis of macrolide oligomycin A. A previous study reported that CYP107W1 regioselectively hydroxylated C12 of oligomycin C to produce oligomycin A, and the crystal structure of ligand free CYP107W1 was determined. Here, we analyzed the structural properties of the CYP107W1-oligomycin A complex and characterized the functional role of the Trp178 residue in CYP107W1. The crystal structure of the CYP107W1 complex with oligomycin A was determined at a resolution of 2.6 A. Oligomycin A is bound in the substrate access channel on the upper side of the prosthetic heme mainly by hydrophobic interactions. In particular, the Trp178 residue in the active site intercalates into the large macrolide ring, thereby guiding the substrate into the correct binding orientation for a productive P450 reaction. A Trp178 to Gly mutation resulted in the distortion of binding titration spectra with oligomycin A, whereas binding spectra with azoles were not affected. The Gly178 mutant's catalytic turnover number for the 12-hydroxylation reaction of oligomycin C was highly reduced. These results indicate that Trp178, located in the open pocket of the active site, may be a critical residue for the productive binding conformation of large macrolide substrates. PMID- 26883909 TI - Injury surveillance and associations with socioeconomic status indicators among youth/young workers in New Jersey secondary schools. AB - BACKGROUND: Injuries involving career-technical-vocational education (CTE) are reported to the New Jersey Safe Schools Program online reporting system, the only U.S. State law-based surveillance data for young workers (ages twenty-one and younger), a susceptible, vulnerable adolescent sub-population. METHODS: We examined potential associations between socioeconomic status (SES) indicators and high school student injuries reported between 12/1998-12/2013, excluding injuries acquired by staff members. Associations between DFG score-a proxy for school/district SES-and variables relating to reported injuries, including severity, injury type, injury cause, body parts injured, injury treatment setting and demographics were examined with chi square test (X(2)) for independence and logistic regression. To assess potential associations between SES and personal protective equipment (PPE), data were stratified by 2003-2008 and 2008-2013, given mandated payment by employers of PPE for employees. RESULTS: Statistically significant associations were found between SES and injury cause [X(2) = (7, 14.74), p = 0.04] and SES and injury treatment setting [X(2) = (1, 4.76), p = 0.03]. Adjusted odds ratio suggested students from low SES schools were at a higher odds of being treated at a hospital emergency department (ED) than students from high SES schools (95 % CI 1.3-4.3, p < 0.01). CONCLUSIONS: These findings indicated low SES schools/districts have increased odds of being treated at ED, after controlling for injury severity. Future research should focus on implications such associations have on health care access and insurance for young workers and their families. With small sample sizes representing lower DFG scoring (SES) schools/districts, additional efforts should be enacted to increase injury reporting in these schools/districts. PMID- 26883906 TI - N-Terminal Acetylation-Targeted N-End Rule Proteolytic System: The Ac/N-End Rule Pathway. AB - Although Nalpha-terminal acetylation (Nt-acetylation) is a pervasive protein modification in eukaryotes, its general functions in a majority of proteins are poorly understood. In 2010, it was discovered that Nt-acetylation creates a specific protein degradation signal that is targeted by a new class of the N-end rule proteolytic system, called the Ac/N-end rule pathway. Here, we review recent advances in our understanding of the mechanism and biological functions of the Ac/N-end rule pathway, and its crosstalk with the Arg/N-end rule pathway (the classical N-end rule pathway). PMID- 26883912 TI - Program and Abstracts of the 13th Transgenic Technology Meeting (TT2016): Clarion Congress Hotel, Prague, Czech Republic, 20-23 March 2016. PMID- 26883910 TI - Death receptor-based enrichment of Cas9-expressing cells. AB - BACKGROUND: The CRISPR/Cas9 genome editing system has greatly facilitated and expanded our capacity to engineer mammalian genomes, including targeted gene knock-outs. However, the phenotyping of the knock-out effect requires a high DNA editing efficiency. RESULTS: Here, we report a user-friendly strategy based on the extrinsic apoptosis pathway that allows enrichment of a polyclonal gene edited cell population, by selecting Cas9-transfected cells that co-express dominant-negative mutants of death receptors. The extrinsic apoptosis pathway can be triggered in many mammalian cell types, and ligands are easy to produce, do not require purification and kill much faster than the state-of-the-art selection drug puromycin. Stringent assessment of our advanced selection strategy via Sanger sequencing, T7 endonuclease I (T7E1) assay and direct phenotyping confirmed a strong and rapid enrichment of Cas9-expressing cell populations, in some cases reaching up to 100 % within one hour. Notably, the efficiency of target DNA cleavage in these enriched cells reached high levels that exceeded the reliable range of the T7E1 assay, a conclusion that can be generalized for editing efficiencies above 30 %. Moreover, our data emphasize that the insertion and deletion pattern induced by a specific gRNA is reproducible across different cell lines. CONCLUSIONS: The workflow and the findings reported here should streamline a wide array of future low- or high-throughput gene knock-out screens, and should largely improve data interpretation from CRISPR experiments. PMID- 26883911 TI - MiRNA-146b-5p upregulates migration and invasion of different Papillary Thyroid Carcinoma cells. AB - BACKGROUND: Tumor invasiveness is directly related to the ability of tumor cells to migrate and invade surrounding tissues, usually degrading extracellular matrix. Despite significant progress in the knowledge about migration and invasion, there is much more to elucidate about their regulatory mechanisms, especially in cancer cells. MicroRNAs (miRs) were recently described as important regulators of migration. Differential expression of miRs in cancer is frequently associated with progression, invasion and metastasis. In papillary thyroid carcinoma (PTC), miR-146b-5p is highly expressed and positively correlated to the degree of malignancy. METHODS: This study aimed to investigate the role of miR 146b-5p on the migratory and invasive behaviors of thyroid cells, using a non tumor rat thyroid follicular cell line (PCCl3) transfected with the miR-146b-5p genomic region, and two PTC cell lines (TPC-1 and BCPAP, bearing distinct oncogenic backgrounds), which express high levels of miR-146b-5p, after miR-146b inhibition by antagomiR and miR-146b overexpression by mimics-miR. Migration and invasion were studied by time-lapse and transwell assays (with and without Matrigel(r)). Gelatin degradation assays were also employed, as well as F-actin staining. RESULTS: Migration and invasion of PCCl3 were increased 2-3x after miR 146b-5p overexpression (10X) and large lamellipodia were evident in those cells. After miR-146b-5p inhibition, TPC-1 and BCPAP migration and invasion were significantly reduced, with cells showing several simultaneous processes and low polarity. Gelatin degradation was inhibited in TPC-1 cells after inhibition of miR-146b-5p, but was unaffected in BCPAP cells, which did not degrade gelatin. The inhibition of miR-146b-5p in PCCl3 also inhibited migration and invasion, and additional (exogenous) overexpression of this miR in TPC-1 and BCPAP cells increased migration and invasion, without effects on cell morphology or gelatin degradation. The overexpression of SMAD4 in BCPAP cells, a validated target of miR-146b-5p and key protein in the TGF-beta signaling pathway, inhibited migration similarly to the effects observed with the antagomiR 146b-5p. CONCLUSIONS: miR-146b-5p positively regulates migration and invasion of thyroid normal and tumor follicular cells (independently from their original mutation, either BRAF or RET/PTC), through a mechanism that involves the actin cytoskeleton but not an increased capacity of matrix degradation. PMID- 26883913 TI - Complex shaped ZnO nano- and microstructure based polymer composites: mechanically stable and environmentally friendly coatings for potential antifouling applications. AB - Since the prohibition of tributyltin (TBT)-based antifouling paints in 2008, the development of environmentally compatible and commercially realizable alternatives is a crucial issue. Cost effective fabrication of antifouling paints with desired physical and biocompatible features is simultaneously required and recent developments in the direction of inorganic nanomaterials could play a major role. In the present work, a solvent free polymer/particle-composite coating based on two component polythiourethane (PTU) and tetrapodal shaped ZnO (t-ZnO) nano- and microstructures has been synthesized and studied with respect to mechanical, chemical and biocompatibility properties. Furthermore, antifouling tests have been carried out in artificial seawater tanks. Four different PTU/t ZnO composites with various t-ZnO filling fractions (0 wt%, 1 wt%, 5 wt%, 10 wt%) were prepared and the corresponding tensile, hardness, and pull-off test results revealed that the composite filled with 5 wt% t-ZnO exhibits the strongest mechanical properties. Surface free energy (SFE) studies using contact angle measurements showed that the SFE value decreases with an increase in t-ZnO filler amounts. The influence of t-ZnO on the polymerization reaction was confirmed by Fourier transform infrared-spectroscopy measurements and thermogravimetric analysis. The immersion tests demonstrated that fouling behavior of the PTU/t-ZnO composite with a 1 wt% t-ZnO filler has been decreased in comparison to pure PTU. The composite with a 5 wt% t-ZnO filler showed almost no biofouling. PMID- 26883914 TI - Raman spectroscopy identifies radiation response in human non-small cell lung cancer xenografts. AB - External beam radiation therapy is a standard form of treatment for numerous cancers. Despite this, there are no approved methods to account for patient specific radiation sensitivity. In this report, Raman spectroscopy (RS) was used to identify radiation-induced biochemical changes in human non-small cell lung cancer xenografts. Chemometric analysis revealed unique radiation-related Raman signatures that were specific to nucleic acid, lipid, protein and carbohydrate spectral features. Among these changes was a dramatic shift in the accumulation of glycogen spectral bands for doses of 5 or 15 Gy when compared to unirradiated tumours. When spatial mapping was applied in this analysis there was considerable variability as we found substantial intra- and inter-tumour heterogeneity in the distribution of glycogen and other RS spectral features. Collectively, these data provide unique insight into the biochemical response of tumours, irradiated in vivo, and demonstrate the utility of RS for detecting distinct radiobiological responses in human tumour xenografts. PMID- 26883915 TI - SpoTyping: fast and accurate in silico Mycobacterium spoligotyping from sequence reads. AB - SpoTyping is a fast and accurate program for in silico spoligotyping of Mycobacterium tuberculosis isolates from next-generation sequencing reads. This novel method achieves high accuracy for reads of both uniform and varying lengths, and is about 20 to 40 times faster than SpolPred. SpoTyping also integrates the function of producing a report summarizing associated epidemiological data from a global database of all isolates having the same spoligotype. SpoTyping is freely available at: https://github.com/xiaeryu/SpoTyping-v2.0 . PMID- 26883917 TI - Prothrombotic Risk Factors and Preventive Strategies in Adolescent Venous Thromboembolism. AB - Venous thromboembolism (VTE) in adolescents is a serious condition that requires prompt recognition and optimal management to prevent mortality and long-term morbidity. Adolescents account for a large proportion of cases of VTE in children. As teenagers transition from childhood to adulthood, they are at risk of developing medical conditions and exposure to risky habits that predispose them to VTE. This review focuses on the variety of risk factors and comorbidities seen in adolescent VTE and takes a quick look into risk-based preventive strategies for primary and secondary prevention. PMID- 26883916 TI - A review of iron studies in overweight and obese children and adolescents: a double burden in the young? AB - INTRODUCTION: The connection between iron and excessive adiposity has received much research interest. Although children and adolescents have unique developmental phases and nutritional demands, to date, reviews of iron in the overweight (OW) and obese (OB) have combined studies of children and adults or have focussed on adults. PURPOSE: The aim of this review was to critically evaluate studies of the relationship between iron and OW and obesity in children and adolescents, with emphasis on iron status, oral iron response, dietary intake and systemic inflammatory markers. METHODS: A PubMed search was conducted to identify relevant articles published up to December 2015. Combinations of the following keywords were used: iron, OW, OB, children, adolescents, diet, hepcidin, inflammation, fortification, supplementation, weight loss, trace elements, obesity, iron deficiency (ID), minerals. RESULTS AND CONCLUSION: A higher prevalence of ID, or risk of ID, among OW and OB children and adolescents has been consistently observed. Chronic inflammation caused by excessive adiposity offers a plausible explanation for this finding, rather than dietary factors. However, future studies must employ screening for the presence of both acute and chronic infections and inflammatory conditions and report other factors such as pubertal status. Intervention studies, although few, indicate that OW and OB children and adolescents have reduced response to oral iron. Further trials are needed to explore the connection between body fat mass, inflammatory proteins and iron absorption, together with the effect of weight loss on iron status in iron-deficient OW and OB children and adolescents. PMID- 26883918 TI - Bovine male germline stem-like cells cultured in serum- and feeder-free medium. AB - Male germline stem cells (mGSCs) presented in male testis are responsible for spermatogenesis during their whole life. However, little information can be found on the culture of bovine mGSCs, and the current culture system needs to be improved. In this study, we compared the effects of several commercial serum-free media and different extra-cellular matrix on the enrichment and cultivation of mGSCs. To find out the best culture condition, the biological characteristics of the cultured cells were evaluated by morphological observation, RT-PCR and immunofluorescent staining. According to the cells' condition in different experiment groups, we found out an efficient cultivation system for bovine mGSCs derived from neonate testis. In this serum- and feeder-free medium, the cultured cells maintained the typical morphology, and expressed specific surface markers of both pluripotent ES cells and mGSCs, including SSEA-1, CD49f, C-MYC, PLZF, GFRalpha1, LIN28, NANOG, Oct4 and SOX2 in commercial human ESCs medium PeproGrow hESC + BIO (6-bromoindirubin-3'-oxime). Embryoid bodies, derived from the bovine mGSCs, and were formed by ganging drop culture. The retinoic acid induced bovine mGSCs were positive for Stra8, SCP3, DZAL, EMA1 and VASA, and resembled spermatid cells morphologically. Thus, we found an efficient bovine mGSCs-cultivation system, which is lack in serum and feeder. PMID- 26883919 TI - Establishment and characterization of a new feline mammary cancer cell line, FkMTp. AB - Studies on tumours in domestic animals are believed to greatly contribute to a better understanding of similar diseases in humans. Comparative studies have shown that feline mammary carcinomas share important features with human breast cancers, including a similar biological behaviour and histological appearance. In the present study we have established and characterized at different cellular levels one feline mammary cancer cell line, FkMTp, derived from a cat mammary carcinoma. The FkMTp cell line revealed to be a promising resource and tool to study tumour microevolution and all the mechanisms and processes involved in carcinogenesis from the tumour (primary culture) to the immortalized cell line. Several assays were conducted to assess the growth behaviour, differentiated morphology, anchorage independent growth in soft agar, wound-healing invasion and migration of the cell line across time (from the primary culture until the 160th passage). FkMTp revealed increased levels of anchorage independence, migration and invasion according to the course of time as well as different numbers of ploidy. These results demonstrate and validate the in vitro tumorigenicity of the FkMTp cell line. During the cell line establishment, it was cryopreserved approximately every six passages, including the tumour primary culture, allowing now the possibility to access almost any specific momento of the tumour progression. PMID- 26883921 TI - Hospital and 4-Year Mortality Predictors in Patients With Acute Pulmonary Edema With and Without Coronary Artery Disease. AB - BACKGROUND: Long-term prognosis of acute pulmonary edema (APE) remains ill defined. METHODS AND RESULTS: We evaluated demographic, echocardiographic, and angiographic data of 806 consecutive patients with APE with (CAD) and without coronary artery disease (non-CAD) admitted from 2000 to 2010. Differences between hospital and long-term mortality and its predictors were also assessed. CAD patients (n=638) were older and had higher incidence of diabetes and peripheral vascular disease than non-CAD (n=168), and lower ejection fraction. Hospital mortality was similar in both groups (26.5% vs 31.5%; P=0.169) but APE recurrence was higher in CAD patients (17.3% vs 6.5%; P<0.001). Age, admission systolic blood pressure, recurrence of APE, and need for inotropics or endotracheal intubation were the main independent predictors of hospital mortality. In contrast, overall mortality (70.0% vs 57.1%; P=0.002) and readmission for nonfatal heart failure after a 45-month follow-up (10-140; 17.3% vs 7.6%; P=0.009) were higher in CAD than in non-CAD patients. Age, peripheral vascular disease, and peak creatine kinase MB during index hospitalization, but not ejection fraction, were the main independent predictors of overall mortality, whereas coronary revascularization or valvular surgery were protective. These interventions were mostly performed during hospitalization index (294 of 307; 96%) and not intervened patients showed a higher risk profile. CONCLUSIONS: Long term mortality in APE is high and higher in CAD than in non-CAD patients. Considering the different in-hospital and long-term mortality predictors herein described, which do not necessarily involve systolic function, it is conceivable that a more aggressive interventional program might improve survival in high-risk patients. PMID- 26883922 TI - Neighborhood and Acute Myocardial Infarction Mortality as Related to the Driving Time to Percutaneous Coronary Intervention-Capable Hospital. AB - BACKGROUND: Driving time to a percutaneous coronary intervention (PCI)-capable hospital is important in timely treatment of acute myocardial infarction (AMI). Our objective was to determine whether driving time from one's residence to a PCI capable hospital contributes to AMI deaths. We conducted a cross-sectional study of age- and sex-adjusted mortality in census block groups to evaluate this question. METHODS AND RESULTS: We studied all (14 027) AMI deaths that occurred during 2008-2012 in Arkansas to assess the relationship between driving time from the population center of a block group (neighborhood) to the nearest PCI-capable hospital. We estimated standardized mortality ratios in block groups that were adjusted for education (population over 25 years of age who did not graduate from high school), poverty (population living below federal poverty level), population density (population per square mile), mobility (population residing at the same address as 1 year ago), black (population that is black), rurality (rural households), geodesic distance, and driving time. The median geodesic distance and driving time were 12.8 miles (interquartile range 3.6-30.1) and 28.3 minutes (interquartile range 9.6-58.7), respectively. Risks in neighborhoods with long driving times (90th percentile) were 26% greater than risks in neighborhoods with short driving times (10th percentile), even after adjusting for education, poverty, population density, rurality, and black race (P<0.0001). CONCLUSIONS: AMI mortality increases with increasing driving time to the nearest PCI-capable hospital. Improving the healthcare system by reducing time to arrive at a PCI capable hospital could reduce AMI deaths. PMID- 26883923 TI - CNS infection caused by Pseudallescheria boydii in a near-drowning traveller from a traffic accident. PMID- 26883924 TI - The tolerability of a combined hepatitis A and typhoid vaccine in children aged 2 16 years: an observational study. AB - BACKGROUND: Combined hepatitis A and typhoid vaccines have been widely used globally and proven to be safe, well tolerated and efficacious in adults. The combined hepatitis A and typhoid vaccine (Vivaxim) available in Australia is licenced for use from age 16 years but the monovalent components are approved for use from age 2 years. Advantages of a single injection have led to widespread 'off-label' use of Vivaxim in children. This study aimed to investigate the tolerability of Vivaxim in children aged 2-16 years. METHODS: A prospective observational study was conducted at Travel Medicine Alliance clinics across Australia. Children who required vaccination for both hepatitis A and typhoid were offered the option of receiving Vivaxim. Parents were contacted 3 days post vaccination and asked to respond to a questionnaire on adverse events following immunization (AEFIs). Reactions to Vivaxim were compared with reported reactions to the monovalent vaccines. RESULTS: Our study included 425 children who received Vivaxim, including 189 (44.5%) who received other vaccines on the same day. No serious AEFIs were reported, and 26.8% did not experience any side effects. In children who did not receive other vaccines in the same arm as Vivaxim (n = 325), most common local reactions were sore arm (70.5%), redness (16.0%) and swelling (11.1%). Reports of local AEFIs in our subjects was significantly more common than those reported for the individual monovalent vaccines. In children who did not receive other vaccines on the same day (n = 236), the most common systemic reactions were tiredness/lethargy/malaise (5.9%), headache (4.2%), fever (3.4%) and sore muscles and joints (3.4%). Fever was more common in children aged <6 years. Less than 5% of children reported missing school, sport or other regular activities. CONCLUSIONS: Vivaxim was well tolerated in children aged 2-16 years. Parents should be advised about AEFIs to Vivaxim so that they can make informed decisions about vaccination options. PMID- 26883925 TI - Response: Malaria chemoprophylaxis and self-reported impact on ability to work. PMID- 26883926 TI - Hypertonic saline in the treatment of corneal jellyfish stings. AB - A 20-year-old male soldier was hit by the jellyfish. The ophthalmic examination revealed that epithelial keratitis and corneal oedema in the right eye. We prescribed 3% NaCl eyedrops and 0.3% Norfloxacin eyedrops in the treatment of the corneal jellyfish stings. Two weeks later, the cornea in the right eye healed. In this case report, 3% NaCl eyedrops was effective in the treatment of acute phase of jellyfish stings of the cornea. PMID- 26883927 TI - International travelers and unintentional fatal drowning in Australia--a 10 year review 2002-12. AB - INTRODUCTION: . Drowning deaths of travelers are commonly reported in the media, creating a perception that they are at a higher risk of drowning than residents. This may be true, due in part to unfamiliarity with the risks posed by the hazard, however there is limited information about drowning deaths of travelers in Australia. This study aims to identify the incidence of drowning among international travelers in Australia and examine the risk factors to inform prevention strategies. METHODS: . Data on unintentional fatal drowning in Australian waterways of victims with a residential postcode from outside Australia were extracted from the Royal Life Saving Society-Australia National Fatal Drowning Database. RESULTS: . Between 1 July 2002 and 30 June 2012 drowning deaths among people known to be international travelers accounted for 4.3% (N = 123) of the 2870 drowning deaths reported in Australian waterways. Key locations for drowning deaths included beaches (39.0%), ocean/harbour (22.0%) and swimming pools (12.2%). Leading activities prior to drowning included swimming (52.0%), diving (17.9%) and watercraft incidents (13.0%). DISCUSSION: . International travelers pose a unique challenge from a drowning prevention perspective. The ability to exchange information on water safety is complicated due to potential language barriers, possible differences in swimming ability, different attitudes to safety in the traveler's home country and culture, a lack of opportunities to discuss safety, a relaxed attitude to safety which may result in an increase in risk taking behaviour and alcohol consumption. CONCLUSION: . Prevention is vital both to reduce loss of life in the aquatic environment and promote Australia as a safe and enjoyable holiday destination for international travelers. PMID- 26883928 TI - Doxorubicin-conjugated CuS nanoparticles for efficient synergistic therapy triggered by near-infrared light. AB - To integrate photothermal therapy (PTT) with chemotherapy for improving anticancer efficiency, we developed a novel and multifunctional doxorubicin (DOX) conjugated copper sulfide nanoparticle (CuS-DOX NP) drug delivery system using hydrazone bonds to conjugate carboxyl-functionalized copper sulfide nanoparticles (CuS NPs) and DOX. On the other hand, the hydrazone bonds could be used for improving the DOX release rate (88.0%) by cleavage in a mildly acidic environment irradiated by 808 nm laser light, which could greatly promote chemo-therapeutic efficacy. Simultaneously, CuS NPs which can absorb near infrared (NIR) light produce a clear thermal effect, giving rise to a synergistic therapeutic effect combined with enhanced chemo-therapy. The DOX-conjugated CuS NPs display an evident in vitro cytotoxicity to HeLa cancer cells under 808 nm light irradiation. High tumor inhibition efficacy has been achieved after 14 day in vivo treatment, performed with intravenous administration of CuS-DOX NPs with 808 nm laser irradiation on H22 tumor-bearing mice. The multifunctional system which was achieved by a facile route should be a potential candidate in the anti-cancer field due to the synergistic therapeutic effect, which is superior to any single approach. PMID- 26883930 TI - Erratum to: Intermittent Obstructive Jaundice Following Gastric Band Placement. PMID- 26883931 TI - Laparoscopic Transgastric Enucleation of a Gastric Leiomyoma near the Esophagogastric Junction and Concomitant Sleeve Gastrectomy: Video Report. AB - BACKGROUND: Obesity and bariatric surgery (BS) are increasing worldwide and can potentially lead to incidental diagnosis of benign gastric tumor including gastric leiomyoma (GL). When indicated, local tumor enucleation, completed through laparoscopic minimal-invasive approaches, has proven to be safe and effective especially when located near the esophagogastric junction (EGJ) with limited morbidity as compared to partial or total gastrectomies. Little is known regarding the most appropriate strategy concerning the management of GL regardless of the location in patients' candidate for BS. METHODS: We present the case of a 67-year-old morbidly obese woman. She presented with an incidental 3-cm GL developed near the EGJ and antral histologic abnormalities mandating a gastric follow-up. Therefore, we performed both laparoscopic transgastric enucleation and sleeve gastrectomy simultaneously. RESULTS: After identification of the lesion, the gastrocolic ligament was divided and a gastrotomy was performed along the greater curvature to expose the tumor. Once the submucosal plan was identified, the lesion was enucleated from the submucosamuscle junction. After closure of the mucosal defect and ensuring the absence of gastric wall perforation, a conventional laparoscopic sleeve gastrectomy was performed. No adverse outcomes occurred during the post-operative period. The final pathologic diagnosis showed a completely resected and benign leiomyoma. CONCLUSION: Herein, we report the first laparoscopic transgastric enucleation of a GL localized close to the EGJ performed concomitant with a sleeve gastrectomy. This combined approach appeared feasible, safe, and do not compromise the access to the GI tract as well as potential future curative treatments on the gastric sleeve. PMID- 26883929 TI - Indications and Operative Outcomes of Gastric Bypass Reversal. AB - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is one of the best-known and most commonly performed bariatric procedures. However, this procedure carries infrequent but serious long-term complications, which may require revisional procedures. This study reports the indications and outcomes of gastric bypass reversal that have not been described well in the literature. METHODS: A multicenter retrospective study of 50 patients who underwent reversal of RYGB conducted between 2006 and 2015 was reviewed to describe the usual indications and outcomes of gastric bypass reversal surgeries. RESULTS: Of 50 patients, 7 (14 %) were males and 43 (86 %) were females. The mean age of the patient population was 40.4 +/- 11.6 years (range 19-66). Reasons for reversal included anastomotic ulcers (n = 27), anastomotic complications (n = 9), malnutrition (n = 2), and functional disorder (n = 12). The mean BMI before the reversal was 29 +/- 9.4 kg/m(2) (range 16-60). The mean time between the primary procedure and reversal was 60 +/- 65.5 months (range 2-300). Fourteen of the reversals were done via laparotomy. Mean hospital stay was 8.4 +/- 7.3 days (range 3-34 days). There was no peri-operative death 30 days after reversal. Following gastric bypass reversal, 92.6 % (n = 25) of the patient population had resolution from ulcers, 77.8 % (n = 7) of the patient population had resolution from anatomic complications, 100 % (n = 2) of the patient population had resolution from malnutrition, and 66.7 % (n = 8) of the patient population had resolution from functional disorders. CONCLUSIONS: Gastric bypass reversal is a reasonable and safe treatment for complications arising from the GBP surgery. A laparoscopic approach is feasible in select patients. PMID- 26883933 TI - Perpendicular magnetic tunnel junctions with a synthetic storage or reference layer: A new route towards Pt- and Pd-free junctions. AB - We report here the development of Pt and Pd-free perpendicular magnetic tunnel junctions (p-MTJ) for STT-MRAM applications. We start by studying a p-MTJ consisting of a bottom synthetic Co/Pt reference layer and a synthetic FeCoB/Ru/FeCoB storage layer covered with an MgO layer. We first investigate the evolution of RKKY coupling with Ru spacer thickness in such a storage layer. The coupling becomes antiferromagnetic above 0.5 nm and its strength decreases monotonously with increasing Ru thickness. This contrasts with the behavior of Co based systems for which a maximum in interlayer coupling is generally observed around 0.8 nm. A thin Ta insertion below the Ru spacer considerably decreases the coupling energy, without basically changing its variation with Ru thickness. After optimization of the non-magnetic and magnetic layer thicknesses, it appears that such a FeCoB/Ru/FeCoB synthetic storage layer sandwiched between MgO barriers can be made stable enough to actually be used as hard reference layer in single or double magnetic tunnel junctions, the storage layer being now a single soft FeCoB layer. Finally, we realize Pt- or Pd-free robust perpendicular magnetic tunnel junctions, still keeping the advantage of a synthetic reference layer in terms of reduction of stray fields at small pillar sizes. PMID- 26883934 TI - Comparison of toxicity profile and tolerability between two standard of care paclitaxel-based adjuvant chemotherapy regimens in breast cancer. AB - In breast cancer, there are two widely used paclitaxel-based adjuvant chemotherapies, either dose dense paclitaxel (ddP) or weekly paclitaxel (wP). To our knowledge, the comparisons of toxicity and tolerability between the two regimens have never been reported in the literature. This is a retrospective single-institution charts review of breast cancer patients who were treated with paclitaxel-based chemotherapy either ddP or wP. In total, 76 and 45 patients with breast cancer received adjuvant standard ddP and wP, respectively. Patient characteristics in both groups were comparable. Our results showed no statistical significant difference in toxicity profile and tolerability between the two regimens. Particularly, chemotherapy-induced peripheral neuropathy (CIPN) was equally observed in both schedules. Furthermore, grade 3 and 4 CIPN was observed in 17 and 18 %, respectively (p = 0.93). In terms of tolerability, both regimens resulted in similar rates of hospitalization and treatment discontinuation. Our data analysis indicates no significant difference in toxicity profile between the two standard paclitaxel regimens in breast cancer. However, this is a small sample-sized retrospective study and further prospective trial with a larger sample size is warranted. PMID- 26883936 TI - Fast hepatic biotransformation of p-synephrine and p-octopamine and implications for their oral intake. AB - Citrus aurantium (bitter orange) extracts have been used in products for weight management and sports performance. These extracts contain large amounts of p synephrine and much smaller amounts of p-octopamine. Both protoalkaloids exert lipolytic and glycogenolytic activities at similar concentrations. The biotransformation of p-synephrine and p-octopamine is not as well-known as those of other adrenergic amines. For this reason transformation of these amines was investigated in the isolated perfused liver. Special attention was devoted to the single pass extraction of each compound as well as to the kinetics of uptake. The assay of the amines in the outflowing perfusate was done by means of high performance liquid chromatography (HPLC). The single pass extraction of p synephrine was higher than 90% at a portal concentration of 10 MUM. It declined with the concentration, but was still around 30% at the concentration of 500 MUM. At low concentrations (10-50 MUM) the decreasing sequence of single pass extractions was p-synephrine > p-octopamine ~ epinephrine > norepinephrine. Rates of uptake versus p-synephrine concentration resulted in a Michaelis-Menten type of relationship, with a KM value of 290.7 +/- 32.1 MUM and a Vmax of 0.762 +/- 0.042 MUmol min(-1) g(-1). The rates of uptake of p-octopamine did not present clear saturation and could be approximated by a linear relationship with a first order rate constant of 1.5 min(-1). The rapid hepatic transformation of p synephrine and p-octopamine means that their concentration in the portal vein exceeds that in the systemic circulation during absorption. Their metabolic effects will, thus, be exerted predominantly in the liver. PMID- 26883935 TI - Adjuvant and neoadjuvant therapies in resectable pancreatic cancer: a systematic review of randomized controlled trials. AB - The timing of surgery and antineoplastic therapies in patients with resectable non-metastatic pancreatic cancer is still a controversial matter of debate, with special regard to neoadjuvant approaches. Following the criteria of the PRISMA statement, a literature search was conducted looking for RCTs focusing on adjuvant and neoadjuvant therapies in resectable pancreatic cancer. The quality of the available evidence was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Data extraction was carried out by two independent investigators. The search led to the identification of 2830 papers of which 14 RCTs focusing on adjuvant and neoadjuvant treatment of resectable pancreatic cancer eligible for the systematic review. Risk of bias was estimated "unclear" in 3 studies and "high" in 5 studies. Median age ranged between 53 and 66. Overall survival in the surgery-only arms ranged between 11 and 20.2 months; in the adjuvant treatment arms 12.5-29.8 months; and in the neoadjuvant setting 9.9 19.4 months. Neoadjuvant protocols should be offered only in randomized clinical trials comparing the standard of care (surgery followed by adjuvant treatments) to a neoadjuvant approach followed by surgery and adjuvant treatment. PMID- 26883937 TI - Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden? AB - BACKGROUND: The aim of this paper is to summarize the available evidence supporting the link between late onset hypogonadism (LOH) and associated common clinical illnesses, focusing on metabolic diseases. The possible benefits or risks related to testosterone replacement therapy (TRT) in these conditions will also be analyzed. METHODS: An extensive Medline search was performed. RESULTS: LOH is closely associated with a worse metabolic profile and a higher cardiovascular risk. The relationship between hypogonadism obesity and insulin resistance is complex and bidirectional. Emerging evidence suggests a positive role of TRT in improving body composition and metabolic outcomes in subjects with LOH. CONCLUSIONS: Despite the aforementioned data, it is not completely known whether reduced testosterone levels in elderly males might play a direct pathogenetic role in these conditions or whether low T and associated morbidities are concomitant conditions, both associated with the aging process. Further and longer studies are advisable to confirm the preliminary results. PMID- 26883938 TI - Large-area perovskite nanowire arrays fabricated by large-scale roll-to-roll micro-gravure printing and doctor blading. AB - Organic-inorganic hybrid halide perovskite nanowires (PNWs) show great potential applications in electronic and optoelectronic devices such as solar cells, field effect transistors and photodetectors. It is very meaningful to fabricate ordered, large-area PNW arrays and greatly accelerate their applications and commercialization in electronic and optoelectronic devices. Herein, highly oriented and ultra-long methylammonium lead iodide (CH3NH3PbI3) PNW array thin films were fabricated by large-scale roll-to-roll (R2R) micro-gravure printing and doctor blading in ambient environments (humility ~45%, temperature ~28 degrees C), which produced PNW lengths as long as 15 mm. Furthermore, photodetectors based on these PNWs were successfully fabricated on both silicon oxide (SiO2) and flexible polyethylene terephthalate (PET) substrates and showed moderate performance. This study provides low-cost, large-scale techniques to fabricate large-area PNW arrays with great potential applications in flexible electronic and optoelectronic devices. PMID- 26883939 TI - Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. AB - Worldwide, more individuals have iron deficiency than any other health problem. Most of those affected are unaware of their lack of iron, in part because detection of iron deficiency has required a blood sample. Here we report a non invasive method to optically measure an established indicator of iron status, red blood cell zinc protoporphyrin, in the microcirculation of the lower lip. An optical fibre probe is used to illuminate the lip and acquire fluorescence emission spectra in ~1 min. Dual-wavelength excitation with spectral fitting is used to distinguish the faint zinc protoporphyrin fluorescence from the much greater tissue background fluorescence, providing immediate results. In 56 women, 35 of whom were iron-deficient, the sensitivity and specificity of optical non invasive detection of iron deficiency were 97% and 90%, respectively. This fluorescence method potentially provides a rapid, easy to use means for point-of care screening for iron deficiency in resource-limited settings lacking laboratory infrastructure. PMID- 26883940 TI - Conflicting demands of abstract and specific visual object processing resolved by frontoparietal networks. AB - Object categorization and exemplar identification place conflicting demands on the visual system, yet humans easily perform these fundamentally contradictory tasks. Previous studies suggest the existence of dissociable visual processing subsystems to accomplish the two abilities-an abstract category (AC) subsystem that operates effectively in the left hemisphere and a specific exemplar (SE) subsystem that operates effectively in the right hemisphere. This multiple subsystems theory explains a range of visual abilities, but previous studies have not explored what mechanisms exist for coordinating the function of multiple subsystems and/or resolving the conflicts that would arise between them. We collected functional MRI data while participants performed two variants of a cue probe working memory task that required AC or SE processing. During the maintenance phase of the task, the bilateral intraparietal sulcus (IPS) exhibited hemispheric asymmetries in functional connectivity consistent with exerting proactive control over the two visual subsystems: greater connectivity to the left hemisphere during the AC task, and greater connectivity to the right hemisphere during the SE task. Moreover, probe-evoked activation revealed activity in a broad frontoparietal network (containing IPS) associated with reactive control when the two visual subsystems were in conflict, and variations in this conflict signal across trials was related to the visual similarity of the cue-probe stimulus pairs. Although many studies have confirmed the existence of multiple visual processing subsystems, this study is the first to identify the mechanisms responsible for coordinating their operations. PMID- 26883941 TI - Association of HLA-G 3' untranslated region variants with type 1 diabetes mellitus. AB - Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+3010C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bpDEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA G. PMID- 26883942 TI - CHANGES IN THE GENETIC STRUCTURE OF A VALLEY IN THE PYRENEES (CATALONIA, SPAIN). AB - In some situations the use of isonymy is the best strategy for studying the genetic structure of a population and its biological history. In this study different population parameters were calculated for one of the most isolated valleys in the Pyrenees - the region of the Alta Ribagorca in Catalonia, Spain. Surnames from marriage records covering the continuous period from 1638 to 1988 were used. From 1950 onwards this region underwent important social, economic and biological changes related to the introduction of hydroelectric and mining industries, and the change from livestock farming to a society based on services. Two periods were analysed (1638-1950 and 1951-1988) allowing population changes that occurred in the region to be determined. The study focused on calculating the number of surnames by gender, diversity index (H), population sub-structure (RP-RPr)/RPr and inbreeding coefficient (F t) and detection of possible genetic barriers. The results demonstrate the importance that geography initially had in shaping the genetic structure of the population and how this was gradually replaced by other parameters such as roads or the social and economic importance of towns. An interesting phenomenon is that inbreeding has traditionally been associated with rural life, isolation and endogamy. However, for the Alta Ribagorca it was observed that in the second period, 1951-1988, inbreeding mainly depended on the composition of migrant groups and the reaction of the native population to the arrival of migrants from outside the region. PMID- 26883944 TI - Reporting treatment outcomes in observational data: A fine balance. AB - Analyses of observational data have been gaining momentum in the evaluation of ever increasing spectrum of disease modifying therapies for multiple sclerosis. While high cost-effectiveness and generalisability represent their main advantages, these studies are also burdened with high risk of bias that may lead to erroneous conclusions. In this viewpoint, we highlight the key role of rigorous and transparent statistical methodology in the studies of observational data and encourage its thorough editorial scrutiny. PMID- 26883943 TI - A serial 10-year follow-up study of brain atrophy and disability progression in RRMS patients. AB - BACKGROUND: We explored the evolution of brain atrophy in relation to development of confirmed disability progression (CDP) on serial 1.5T magnetic resonance imaging (MRI) scans over a 10-year period in 181 patients with early relapsing remitting multiple sclerosis (RRMS). METHODS: At 10-year follow-up, they were divided into those with (100) or without (76) CDP (confirmed after 48 weeks). Changes in whole brain (WB), cortical, gray matter (GM), white matter, and ventricular cerebrospinal fluid (vCSF) volumes were calculated on three dimensional T1-weighted (3D-T1) scans between all available time points. RESULTS: In multiple sclerosis (MS) patients with CDP compared to those without, the greatest effect size percentage volume change from baseline to follow-up was detected for WB (d = 0.55, -7.5% vs -5.2%, p < 0.001), followed by vCSF (d = 0.51, +41.1% vs +25.7%, p < 0.001), cortical (d = 0.49, -7.7% vs -6.2%, p = 0.001), and GM (d = 0.40, -7.1% vs -5.8%, p = 0.006) volumes. Mixed-effects model analysis, adjusted for age, sex, and treatment change, showed significant interactions between CDP status and percentage changes for WB and vCSF (p < 0.001), cortical (p = 0.02), and GM (p = 0.04) volumes. CONCLUSIONS: WB and cortical atrophy, and enlargement of vCSF spaces are associated with development of CDP on serial yearly MRI assessments over a period of 10 years. PMID- 26883945 TI - Abnormal galactosylation of immunoglobulin G in cerebrospinal fluid of multiple sclerosis patients. AB - BACKGROUND: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis. OBJECTIVES: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis. METHODS: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease. A lectin-based assay was used to investigate potential galactosylation modifications of immunoglobulin G. RESULTS AND CONCLUSION: Galactosylation of immunoglobulin G isolated from cerebrospinal fluid of control patients was found to be age- and gender-dependent. In addition, immunoglobulin G galactosylation was significantly altered in cerebrospinal fluid but not in serum of multiple sclerosis patients. Furthermore, this modification was correlated with an active progression of multiple sclerosis. Finally, the loss of galactosyl moieties was not simply associated with inflammation as no such change was detected in viral meningitis patients characterized by brain inflammation. PMID- 26883947 TI - Thermal plasticity in farmed, wild and hybrid Atlantic salmon during early development: has domestication caused divergence in low temperature tolerance? AB - BACKGROUND: In the past three decades, millions of domesticated Atlantic salmon Salmo salar L. have escaped from farms into the wild. Their offspring display reduced survival in the natural environment, which demonstrates that gene-flow is likely to have a negative effect on wild populations. However, inter-population differences in introgression of farmed salmon have been observed, and the underlying ecological mechanisms remain enigmatic. We hypothesised that domestication-driven divergence in tolerance to low temperatures during early development may contribute to lower survival of farmed salmon offspring in the wild, which in turn, may influence patterns of introgression among populations exposed to different temperature regimes. We reared the offspring of 35 families of wild, farmed and hybrid origin at three temperatures (3.9, 5.6 and 12 degrees C) from the onset of exogenous feeding and throughout their first summer. Thermal reaction norms for growth and survival were investigated along the gradient. RESULTS: The main results of this study, which is based upon the analysis of juvenile salmon from five wild strains, two farmed strains and two hybrid strains, can be summarised as; (i) salmon of all origins were able to successfully initiate feeding at all temperatures and similar survival reaction norms were detected in all strains across the temperature gradient; (ii) deviating growth reaction norms were detected between strains, although this result was most likely due to an overall lack of growth in the lower temperature treatments. CONCLUSIONS: This study revealed no evidence of domesticated-driven divergence in low temperature tolerance in Atlantic salmon during early development. Although the potential interaction between low temperature and other river-specific factors cannot be excluded, our results indicate that the reduced survival of farmed offspring in the wild is not explained by farmed salmon displaying impaired abilities to initiate feeding at low temperatures. We therefore suggest that the observed inter-population patterns of introgression are not low-temperature driven and that other ecological or biological factors may explain why detection of farmed salmon in wild rivers is not synonymous with introgression. In general, our results support the literature indicating that phenotypic plasticity instead of thermal adaption has been selected for in Atlantic salmon. PMID- 26883948 TI - Biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. AB - The aim of this study was to evaluate the in vitro and in vivo biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. In vitro cytotoxicity tests by cholecystokinin octapeptide (CCK-8) assay showed that the 5%Van-MSN-CaSO4 and Van-CaSO4 bone cements were cytocompatible for mouse osteoblastic cell line MC3T3-E1. The microscopic observation confirmed that MC3T3-E1cells incubated with Van-CaSO4 group and 5%Van-MSN-CaSO4 group exhibited clear spindle-shaped changes, volume increase and maturation, showing that these cements supported adhesion of osteoblastic cells on their surfaces. In addition, the measurement of alkaline phosphatase activity revealed the osteoconductive property of these biomaterials. In order to assess in vivo biocompatibility, synthesized cements were implanted into the distal femur of twelve adult male and female New Zealand rabbits. After implantation in artificial defects of the distal femur, 5%Van-MSN-CaSO4 and Van CaSO4 bone cements did not damage the function of main organs of rabbits. In addition, the Van-MSN-CaSO4 composite allowed complete repair of bone defects with new bone formation 3 months after implantation. These results show potential application of Van-MSN-CaSO4 composites as bone graft materials for the treatment of open fracture in human due to its mechanical, osteoconductive and potential sustained drug release characteristics and the absence of adverse effects on the body. PMID- 26883946 TI - Phosphate induces formation of matrix vesicles during odontoblast-initiated mineralization in vitro. AB - Mineralization is a process of deposition of calcium phosphate crystals within a fibrous extracellular matrix (ECM). In mineralizing tissues, such as dentin, bone and hypertrophic cartilage, this process is initiated by a specific population of extracellular vesicles (EV), called matrix vesicles (MV). Although it has been proposed that MV are formed by shedding of the plasma membrane, the cellular and molecular mechanisms regulating formation of mineralization-competent MV are not fully elucidated. In these studies, 17IIA11, ST2, and MC3T3-E1 osteogenic cell lines were used to determine how formation of MV is regulated during initiation of the mineralization process. In addition, the molecular composition of MV secreted by 17IIA11 cells and exosomes from blood and B16-F10 melanoma cell line was compared to identify the molecular characteristics distinguishing MV from other EV. Western blot analyses demonstrated that MV released from 17IIA11 cells are characterized by high levels of proteins engaged in calcium and phosphate regulation, but do not express the exosomal markers CD81 and HSP70. Furthermore, we uncovered that the molecular composition of MV released by 17IIA11 cells changes upon exposure to the classical inducers of osteogenic differentiation, namely ascorbic acid and phosphate. Specifically, lysosomal proteins Lamp1 and Lamp2a were only detected in MV secreted by cells stimulated with osteogenic factors. Quantitative nanoparticle tracking analyses of MV secreted by osteogenic cells determined that standard osteogenic factors stimulate MV secretion and that phosphate is the main driver of their secretion. On the molecular level, phosphate-induced MV secretion is mediated through activation of extracellular signal-regulated kinases Erk1/2 and is accompanied by re-organization of filamentous actin. In summary, we determined that mineralization-competent MV are distinct from exosomes, and we identified a new role of phosphate in the process of ECM mineralization. These data provide novel insights into the mechanisms of MV formation during initiation of the mineralization process. PMID- 26883951 TI - Formal [4 + 1] Cycloadditions of beta,beta-Diaryl-Substituted ortho (Alkynyl)styrenes through Gold(I)-Catalyzed Cycloisomerization Reactions. AB - Gold(I)-catalyzed cycloisomerization of beta,beta-diaryl-o-(alkynyl)styrenes at 80 degrees C selectively yields dihydroindeno[2,1-a]indenes in a transformation that encompasses a formal [4 + 1] cycloaddition and takes place through a cascade 5-endo-cyclization-diene activation-iso-Nazarov cyclization. In addition, by performing the reaction at 0 degrees C, the same substrates exclusively give rise to benzofulvene derivatives, which have also been shown to be intermediates in the formation of the tetracyclics. PMID- 26883949 TI - Development of three-dimensional tissue engineered bone-oral mucosal composite models. AB - Tissue engineering of bone and oral mucosa have been extensively studied independently. The aim of this study was to develop and investigate a novel combination of bone and oral mucosa in a single 3D in vitro composite tissue mimicking the natural structure of alveolar bone with an overlying oral mucosa. Rat osteosarcoma (ROS) cells were seeded into a hydroxyapatite/tri-calcium phosphate scaffold and bone constructs were cultured in a spinner bioreactor for 3 months. An engineered oral mucosa was fabricated by air/liquid interface culture of immortalized OKF6/TERET-2 oral keratinocytes on collagen gel-embedded fibroblasts. EOM was incorporated into the engineered bone using a tissue adhesive and further cultured prior to qualitative and quantitative assessments. Presto Blue assay revealed that ROS cells remained vital throughout the experiment. The histological and scanning electron microscope examinations showed that the cells proliferated and densely populated the scaffold construct. Micro computed tomography (micro-CT) scanning revealed an increase in closed porosity and a decrease in open and total porosity at the end of the culture period. Histological examination of bone-oral mucosa model showed a relatively differentiated parakeratinized epithelium, evenly distributed fibroblasts in the connective tissue layer and widely spread ROS cells within the bone scaffold. The feasibility of fabricating a novel bone-oral mucosa model using cell lines is demonstrated. Generating human 'normal' cell-based models with further characterization is required to optimize the model for in vitro and in vivo applications. PMID- 26883950 TI - Do we need oxytocin to treat schizophrenia? A randomized clinical trial. AB - BACKGROUND: Schizophrenia is a disabling complex mental disorder and despite all available treatment, many patients unfortunately remain partial- or non responders. A large body of research has shown that oxytocin is an important prosocial peptide and there is initial evidence that the central oxytocin system is altered in several mental disorders. The aim of this study was to test the efficacy of oxytocin, as augmentation therapy, in a sample of patients with schizophrenia. METHODS: We conducted an 8-month randomized, double-blind, controlled trial with a crossover design. We wanted to test the hypothesis that intranasal oxytocin could reduce symptoms in 32 patients with schizophrenia aged 18-45 with short-medium illness duration (<11 years). Patients were randomly assigned to either 40 International Units oxytocin once daily or a vehicle placebo group, in addition to their pre-study antipsychotic medication regimen. We subsequently conducted a multi-dimensional assessment including psychopathological, psychosocial and neuropsychological aspects. RESULTS: Positive and Negative Syndrome Scale scores showed no significant differences in treatment effects between the experimental group and controls. Furthermore, no treatment effects were shown in any of the rating scales used in this study. However, a statistically significant period effect was shown in most outcome measurements. CONCLUSIONS: In our trial, oxytocin did not add any significant beneficial effects to anti-psychotic treatment in terms of clinical symptoms or psychosocial functioning. Further research should focus on different ways to administer oxytocin, or investigate predictors (such as past traumas, or biomarkers), which could identify subgroups of patients with different treatment responses to oxytocin. ClinicalTrials.gov Identifier: NCT01699997. ID number: RF 2010-2311148. URL: https://clinicaltrials.gov/ct2/show/NCT01699997. PMID- 26883952 TI - Application of Recombinant Proteins for Serodiagnosis of Visceral Leishmaniasis in Humans and Dogs. AB - Visceral leishmaniasis (VL) is a zoonotic disease caused by leishmania species. Dogs are considered to be the main reservoir of VL. A number of methods and antigen-based assays are used for the diagnosis of leishmaniasis. However, currently available methods are mainly based on direct examination of tissues for the presence of parasites, which is highly invasive. A variety of serological tests are commonly applied for VL diagnosis, including indirect fluorescence antibody test, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, direct agglutination test, Western-blotting, and immunochromatographic test. However, when soluble antigens are used, serological tests are less specific due to cross reactivity with other parasitic diseases. Several studies have attempted to replace soluble antigens with recombinant proteins to improve the sensitivity and the specificity of the immunodiagnostic tests. Major technological advances in recombinant antigens as reagents for the serological diagnosis of VL have led to high sensitivity and specificity of these serological tests. A great number of recombinant proteins have been shown to be effective for the diagnosis of leishmania infection in dogs, the major reservoir of L. infantum. Although few recombinant proteins with high efficacy provide reasonable results for the diagnosis of human and canine VL, more optimization is still needed for the appropriate antigens to provide high-throughput performance. This review aims to explore the application of different recombinant proteins for the serodiagnosis of VL in humans and dogs. PMID- 26883954 TI - Erythropoietin stimulating agents do not significantly improve quality of life in chronic kidney disease, study finds. PMID- 26883953 TI - A SUMO-acetyl switch in PXR biology. AB - Post-translational modification (PTM) of nuclear receptor superfamily members regulates various aspects of their biology to include sub-cellular localization, the repertoire of protein-binding partners, as well as their stability and mode of degradation. The nuclear receptor pregnane X receptor (PXR, NR1I2) is a master regulator of the drug-inducible gene expression in liver and intestine. The PXR mediated gene activation program is primarily recognized to increase drug metabolism, drug transport, and drug efflux pathways in these tissues. The activation of PXR also has important implications in significant human diseases including inflammatory bowel disease and cancer. Our recent investigations reveal that PXR is modified by multiple PTMs to include phosphorylation, SUMOylation, and ubiquitination. Using both primary cultures of hepatocytes and cell-based assays, we show here that PXR is modified through acetylation on lysine residues. Further, we show that increased acetylation of PXR stimulates its increased SUMO modification to support active transcriptional suppression. Pharmacologic inhibition of lysine de-acetylation using trichostatin A (TSA) alters the sub cellular localization of PXR in cultured hepatocytes, and also has a profound impact upon PXR transactivation capacity. Both the acetylation and SUMOylation status of the PXR protein is affected by its ability to associate with the lysine de-acetylating enzyme histone de-acetylase (HDAC)3 in a complex with silencing mediator of retinoic acid and thyroid hormone receptor (SMRT). Taken together, our data support a model in which a SUMO-acetyl 'switch' occurs such that acetylation of PXR likely stimulates SUMO-modification of PXR to promote the active repression of PXR-target gene expression. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID- 26883955 TI - Design of pH-Responsive Biomaterials to Enable the Oral Route of Hematological Factor IX. AB - The oral administration of hematological factor IX (FIX) can offer a convenient prophylactic treatment for hemophilia B patients. pH-Responsive hydrogels based on poly(methacrylic acid)-grafted-poly(ethylene glycol) (P(MAA-g-EG)) have been engineered as delivery vehicles for FIX. In oral delivery, such hydrogel carriers protected FIX from the gastric environment and released it under intestinal conditions as demonstrated by evaluation of the loading and release of FIX. Tailoring of the hydrogel networks improved the loading of FIX within the microcarriers, which is critical for minimizing protein degradation. Optimizing the loading conditions by increasing the incubation time and using a reduced ionic strength buffer further improved the delivery potential of the microcarriers. The presence of the microcarriers significantly enhanced the oral absorption of FIX in vitro. As shown in this work, P(MAA-g-EG) microcarriers are promising candidates for the oral delivery of FIX. PMID- 26883956 TI - Viscoelastic Response of the Human Lower Back to Passive Flexion: The Effects of Age. AB - Low back pain is a leading cause of disability in the elderly. The potential role of spinal instability in increasing risk of low back pain with aging was indirectly investigated via assessment of age-related differences in viscoelastic response of lower back to passive deformation. The passive deformation tests were conducted in upright standing posture to account for the effects of gravity load and corresponding internal tissues responses on the lower back viscoelastic response. Average bending stiffness, viscoelastic relaxation, and dissipated energy were quantified to characterize viscoelastic response of the lower back. Larger average bending stiffness, viscoelastic relaxation and dissipated energy were observed among older vs. younger participants. Furthermore, average bending stiffness of the lower back was found to be the highest around the neutral standing posture and to decrease with increasing the lower back flexion angle. Larger bending stiffness of the lower back at flexion angles where passive contribution of lower back tissues to its bending stiffness was minimal (i.e., around neutral standing posture) highlighted the important role of active vs. passive contribution of tissues to lower back bending stiffness and spinal stability. As a whole our results suggested that a diminishing contribution of passive and volitional active subsystems to spinal stability may not be a reason for higher severity of low back pain in older population. The role of other contributing elements to spinal stability (e.g., active reflexive) as well as equilibrium-based parameters (e.g., compression and shear forces under various activities) in increasing severity of low back pain with aging should be investigated in future. PMID- 26883958 TI - Disruption of brain zinc homeostasis promotes the pathophysiological progress of Alzheimer's disease. AB - Zinc is abundant in the brain, where it plays an important role in synaptic plasticity and in learning; however, excessive zinc is toxic to neuronal cells, and dyshomeostasis of zinc in the brain is a contributing factor for Alzheimer's disease (AD). Deposition of zinc has been detected in senile plaques in the form of zinc-Abeta (beta-amyloid) complexes. Recent studies have demonstrated that zinc exposure to the brain enhances beta-amyloid precursor protein (APP) expression, amyloidogenic APP cleavage and plaque burden. Furthermore, alterations in zinc transporters, which are responsible for zinc homeostasis, occur in AD human brain and transgenic mouse models. These suggest that abnormal brain zinc homeostasis is involved in the pathophysiological progress of AD. PMID- 26883957 TI - Pregnancy and delivery under the MELAS mutation. PMID- 26883960 TI - Effects of light and nutrients on periphyton and the fatty acid composition and somatic growth of invertebrate grazers in subtropical streams. AB - Algal polyunsaturated fatty acids (PUFA), essential for somatic growth and reproduction of aquatic animals, are influenced by ambient environmental conditions, including light and nutrients. Few studies have addressed the extent to which changes in algal PUFA can influence stream herbivore PUFA profiles and the implications for stream food webs. We manipulated subtropical stream periphyton by applying two light levels (open and shaded canopy) and two nutrient regimes (ambient and enriched) to investigate the response of PUFA and somatic growth in stream herbivores. After 6 weeks, the relative content of periphyton PUFA (%) changed distinctly and differed among treatments. Periphyton in the control treatment with open canopy showed a decline in eicosapentaenoic acid (EPA) relative to initial conditions, whereas shading increased EPA and total highly unsaturated FA (HUFA), but decreased alpha-linolenic acid (ALA), linoleic acid and total C18 PUFA. The interaction of open canopy and added nutrients increased periphyton ALA compared with initial conditions, while the combined effects of shading and added nutrients led to greater total HUFA. FA similarity between stream grazers (the mayfly Austrophlebioides and caddisfly Helicopsyche) and periphyton increased with periphyton HUFA content. In addition, the growth of large instars of both grazers also increased in response to increased periphyton HUFA %. Our findings show that environmental changes, associated with riparian canopy and nutrients, can lead to changes in periphyton PUFA composition that in turn affect growth and PUFA composition in stream grazers. PMID- 26883959 TI - Tracking the immunopathological response to Pseudomonas aeruginosa during respiratory infections. AB - Repeated cycles of infections, caused mainly by Pseudomonas aeruginosa, combined with a robust host immune response and tissue injury, determine the course and outcome of cystic fibrosis (CF) lung disease. As the disease progresses, P. aeruginosa adapts to the host modifying dramatically its phenotype; however, it remains unclear whether and how bacterial adaptive variants and their persistence influence the pathogenesis and disease development. Using in vitro and murine models of infection, we showed that P. aeruginosa CF-adaptive variants shaped the innate immune response favoring their persistence. Next, we refined a murine model of chronic pneumonia extending P. aeruginosa infection up to three months. In this model, including CFTR-deficient mice, we unveil that the P. aeruginosa persistence lead to CF hallmarks of airway remodelling and fibrosis, including epithelial hyperplasia and structure degeneration, goblet cell metaplasia, collagen deposition, elastin degradation and several additional markers of tissue damage. This murine model of P. aeruginosa chronic infection, reproducing CF lung pathology, will be instrumental to identify novel molecular targets and test newly tailored molecules inhibiting chronic inflammation and tissue damage processes in pre-clinical studies. PMID- 26883961 TI - Amniotic fluid embolism complicating medical termination of pregnancy. AB - BACKGROUND: Amniotic fluid embolism is always a severe complication and generally occurs during labour or immediately after childbirth. CLINICAL FEATURES: We report the case of a patient falling victim to amniotic fluid embolism after the medical termination of her pregnancy at 24 weeks of amenorrhea following the discovery of a teratoma-carrying foetus. The amniotic fluid embolism diagnosis was strongly suspected in the face of the sudden onset of severe arterial hypotension, hypoxic respiratory distress, a coma state and disseminated intravascular coagulopathy immediately after the delivery. Additional tests were conducted to support the diagnosis: cytological testing of a peripheral venous sample and maternal broncho-alveolar lavage fluid, dosing of tryptase and alpha fetoprotein levels as well as screening for insulin-like growth factor binding protein 1. CONCLUSION: Amniotic fluid embolism is a rare and difficult diagnosis, especially in unconventional settings, yet it can be facilitated by screening for amniotic markers and tryptase. PMID- 26883962 TI - The "William Tell" sign: difficult airway resulting from cranial transfixion by an arrow. PMID- 26883963 TI - Dosing and efficacy of intranasal dexmedetomidine sedation for pediatric transthoracic echocardiography: a retrospective study. AB - PURPOSE: We designed this retrospective observational study on the use of alpha2 agonist dexmedetomidine to determine the optimum intranasal dose to achieve sedation for pediatric transthoracic echocardiography and to identify any dose related adverse effects. METHODS: Outpatient children aged three months to three years with diverse diagnoses of congenital heart disease, including cyanotic cardiac defects, underwent transthoracic echocardiography under dexmedetomidine sedation. Aerosolized intranasal dexmedetomidine was administered with initial doses ranging from 1-3 ug.kg(-1). A rescue dose of 1 ug.kg(-1) was administered if adequate sedation was not achieved within 45 min following the first dose. The primary study outcome was the achievement of adequate sedation to allow transthoracic echocardiography (TTE) scanning, including subxiphoid and suprasternal probe manipulation. RESULTS: Sedation with intranasal dexmedetomidine for transthoracic echocardiography was successful in 62 of the 63 (98%) patients studied, with an intranasal rescue dose required in 13 (21%) patients. Intranasal doses of dexmedetomidine 2.5-3.0 ug.kg(-1) were required for tolerating TTE probe placement, including subxiphoid and suprasternal manipulation, with minimal response and a 90% success rate. Excluding patients who required a second dose of dexmedetomidine, the mean (standard deviation) time from administration to achieving such sedation (onset time) was 26 (8) min for low-dose (1-2 ug.kg(-1)) dexmedetomidine and 28 (8) min for moderate-dose (2.5 3.0 ug.kg(-1)) dexmedetomidine (P = 0.33). Time from administration of low-dose dexmedetomidine to discharge, including TTE scan time, was 80 (14) min, and it increased with moderate-dose dexmedetomidine to 91 (22) min (P = 0.05). Mild to moderate bradycardia and hypotension were observed, but no interventions were required. CONCLUSION: We found that aerosolized intranasal dexmedetomidine offers satisfactory conditions for TTE in children three months to three years of age with an optimal dose of 2.5-3.0 ug.kg(-1)administered under the supervision of a pediatric cardiac anesthesiologist. PMID- 26883964 TI - Changes in group treatment procedures of Danish finishers and its influence on the amount of administered antimicrobials. AB - When treating groups of pigs orally, antimicrobials can be administered through either feed or water. During the last decade, the group treatment procedure for finishers has shifted from feed to water administration. We hypothesized that farms implementing this change in treatment procedure would increase their total amount of administered antimicrobials. Based on Danish national register data, we performed a retrospective cohort study with three groups. The cohort of primary interest (Cohort Change) consisted of 50 finisher farms which changed their group treatment procedure from feed administration to water administration between 2008 and 2009. In addition, we identified 221 farms where treatment was administered through feed (Cohort Feed), and another 553 farms where treatment was administered through water (Cohort Water). Both of these groups retained their original treatment procedure throughout the study period. Cohort Change experienced a significant increase in the total amount of prescribed antimicrobials between the years. This increase might be caused by the treatment of more pigs, since antimicrobials administered through the feed are mainly administered at the pen level, while antimicrobials administered in water are mainly administered at the section level. However, we cannot exclude that a change in clinical disease has influenced the amount of prescribed antimicrobials. No change was observed in the other two cohorts. Furthermore, the difference in the amount of prescribed antimicrobials between the years was significantly different in Cohort Change when compared to both Cohort Water and Cohort Feed. Results from this study demonstrate that farms changing their procedure of group treatment from feed administration to water administration may increase their overall use of antimicrobials. PMID- 26883966 TI - Optimizing Nutrition Education in WIC: Findings From Focus Groups With Arizona Clients and Staff. AB - OBJECTIVE: To understand staff and clients' experiences with delivering and receiving nutrition education in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Focus groups involving WIC staff, clients, and former clients in Arizona. Client and staff perceptions of WIC nutrition education, preferences, and suggestions for improvement were examined. Transcripts were analyzed using a deductive thematic approach to identify emerging themes. RESULTS: Findings from 10 focus groups with 25 WIC staff and 29 clients suggested that existing materials were time-consuming and unresponsive to client needs, and additional resources were needed to engage children while parents were in session; new delivery formats for nutrition education, including videos and interactive demonstrations focused on child-friendly preparations of WIC foods, were preferred. CONCLUSIONS AND IMPLICATIONS: Collaboration among existing nutrition education programs, including Supplemental Nutrition Assistance Program-Education, Expanded Food and Nutrition Education Program, community gardens, and Head Start, can complement and enhance WIC nutrition educations in this region. PMID- 26883965 TI - Using social network analysis to inform disease control interventions. AB - Contact patterns between individuals are an important determinant for the spread of infectious diseases in populations. Social network analysis (SNA) describes contact patterns and thus indicates how infectious pathogens may be transmitted. Here we explore network characteristics that may inform the development of disease control programes. This study applies SNA methods to describe a livestock movement network of 180 farms in New Zealand from 2006 to 2010. We found that the number of contacts was overall consistent from year to year, while the choice of trading partners tended to vary. This livestock movement network illustrated how a small number of farms central to the network could play a potentially dominant role for the spread of infection in this population. However, fragmentation of the network could easily be achieved by "removing" a small proportion of farms serving as bridges between otherwise isolated clusters, thus decreasing the probability of large epidemics. This is the first example of a comprehensive analysis of pastoral livestock movements in New Zealand. We conclude that, for our system, recording and exploiting livestock movements can contribute towards risk-based control strategies to prevent and monitor the introduction and the spread of infectious diseases in animal populations. PMID- 26883967 TI - Increased risk of muscle tears below physiological temperature ranges. AB - OBJECTIVES: Temperature is known to influence muscle physiology, with the velocity of shortening, relaxation and propagation all increasing with temperature. Scant data are available, however, regarding thermal influences on energy required to induce muscle damage. METHODS: Gastrocnemius and soleus muscles were harvested from 36 male rat limbs and exposed to increasing impact energy in a mechanical test rig. Muscle temperature was varied in 5 degrees C increments, from 17 degrees C to 42 degrees C (to encompass the in vivo range). The energy causing non-recoverable deformation was recorded for each temperature. A measure of tissue elasticity was determined via accelerometer data, smoothed by low-pass fifth order Butterworth filter (10 kHz). Data were analysed using one way analysis of variance (ANOVA) and significance was accepted at p = 0.05. RESULTS: The energy required to induce muscle failure was significantly lower at muscle temperatures of 17 degrees C to 32 degrees C compared with muscle at core temperature, i.e., 37 degrees C (p < 0.01). During low-energy impacts there were no differences in muscle elasticity between cold and warm muscles (p = 0.18). Differences in elasticity were, however, seen at higher impact energies (p < 0.02). CONCLUSION: Our findings are of particular clinical relevance, as when muscle temperature drops below 32 degrees C, less energy is required to cause muscle tears. Muscle temperatures of 32 degrees C are reported in ambient conditions, suggesting that it would be beneficial, particularly in colder environments, to ensure that peripheral muscle temperature is raised close to core levels prior to high-velocity exercise. Thus, this work stresses the importance of not only ensuring that the muscle groups are well stretched, but also that all muscle groups are warmed to core temperature in pre-exercise routines.Cite this article: Professor A. H. R. W. Simpson. Increased risk of muscle tears below physiological temperature ranges. Bone Joint Res 2016;5:61-65. doi: 10.1302/2046-3758.52.2000484. PMID- 26883968 TI - Comparative metabolite profiling and fingerprinting of genus Passiflora leaves using a multiplex approach of UPLC-MS and NMR analyzed by chemometric tools. AB - Passiflora incarnata as well as some other Passiflora species are reported to possess anxiolytic and sedative activity and to treat various CNS disorders. The medicinal use of only a few Passiflora species has been scientifically verified. There are over 400 species in the Passiflora genus worldwide, most of which have been little characterized in terms of phytochemical or pharmacological properties. Herein, large-scale multi-targeted metabolic profiling and fingerprinting techniques were utilized to help gain a broader insight into Passiflora species leaves' chemical composition. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) spectra of extracted components derived from 17 Passiflora accessions and from different geographical origins were analyzed using multivariate data analyses. A total of 78 metabolites were tentatively identified, that is, 20 C-flavonoids, 8 O-flavonoids, 21 C, O flavonoids, 2 cyanogenic glycosides, and 23 fatty acid conjugates, of which several flavonoid conjugates are for the first time to be reported in Passiflora spp. To the best of our knowledge, this study provides the most complete map for secondary metabolite distribution within that genus. Major signals in (1)H-NMR and MS spectra contributing to species discrimination were assigned to those of C flavonoids including isovitexin-2"-O-xyloside, luteolin-C-deoxyhexoside-O hexoside, schaftoside, isovitexin, and isoorientin. P. incarnata was found most enriched in C-flavonoids, justifying its use as an official drug within that genus. Compared to NMR, LC-MS was found more effective in sample classification based on genetic and/ or geographical origin as revealed from derived multivariate data analyses. Novel insight on metabolite candidates to mediate for Passiflora CNS sedative effects is also presented. PMID- 26883969 TI - Molecular formula assignment for dissolved organic matter (DOM) using high-field FT-ICR-MS: chemical perspective and validation of sulphur-rich organic components (CHOS) in pit lake samples. AB - Molecular formula assignment is one of the key challenges in processing high field Fourier transform ion cyclotron resonance mass spectrometric (FT-ICR-MS) datasets. The number of potential solutions for an elemental formula increases exponentially with increasing molecular mass, especially when non-oxygen heteroatoms like N, S or P are included. A method was developed from the chemical perspective and validated using a Suwannee River Fulvic Acid (SRFA) dataset which is dominated by components consisting exclusively of C, H and O (78 % CHO). In order to get information on the application range and robustness of this method, we investigated a FT-ICR-MS dataset which was merged from 18 mine pit lake pore waters and 3 river floodplain soil waters. This dataset contained 50 % CHO and 18 % CHOS on average, whereas the former SRFA dataset contained only 1.5 % CHOS. The mass calculator was configured to allow up to five nitrogen atoms and up to one sulphur atom in assigning formulas to mass peaks. More than 50 % multiple-formula assignments were found for peaks with masses > 650 Da. Based on DBE - O frequency diagrams, many CHO, CHOS1, CHON1 and CHON1S1 molecular series were ultimately assigned to many m/z and considered to be reliable solutions. The unequivocal data pool could thus be enlarged by 523 (6.8 %) CHOS1 components. In contrast to the method validation with CHO-rich SRFA, validation with sulphur-rich pit lake samples showed that formulas with a higher number of non-oxygen heteroatoms can be more reliable assignments in many cases. As an example: CHOS molecular series were reliable and the CHO classes were unreliable amongst other molecular classes in many multiple-formula assignments from the sulphur-rich pit lake samples. Graphical abstract An exemplary frequency versus DBE - O diagram. CHOS components but not CHO (and not CHON2 or CHON2S) components were considered here reliable. PMID- 26883970 TI - Art and Plastic Surgery. AB - The roots of science and art of plastic surgery are very antique. Anatomy, drawing, painting, and sculpting have been very important to the surgery and medicine development over the centuries. Artistic skills besides shape, volume, and lines perception can be a practical aid to the plastic surgeons' daily work. An overview about the interactions between art and plastic surgery is presented, with a few applications to rhinoplasty, cleft lip, and other reconstructive plastic surgeries. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26883971 TI - Plastic Surgery Statistics in the US: Evidence and Implications. AB - BACKGROUND: The American Society of Plastic Surgeons publishes yearly procedural statistics, collected through questionnaires and online via tracking operations and outcomes for plastic surgeons (TOPS). The statistics, disaggregated by U.S. region, leave two important factors unaccounted for: (1) the underlying base population and (2) the number of surgeons performing the procedures. The presented analysis puts the regional distribution of surgeries into perspective and contributes to fulfilling the TOPS legislation objectives. METHODS: ASPS statistics from 2005 to 2013 were analyzed by geographic region in the U.S. Using population estimates from the 2010 U.S. Census Bureau, procedures were calculated per 100,000 population. Then, based on the ASPS member roster, the rate of surgeries per surgeon by region was calculated and the interaction of these two variables was related to each other. RESULTS: In 2013, 1668,420 esthetic surgeries were performed in the U.S., resulting in the following ASPS ranking: 1st Mountain/Pacific (Region 5; 502,094 procedures, 30 % share), 2nd New England/Middle Atlantic (Region 1; 319,515, 19 %), 3rd South Atlantic (Region 3; 310,441, 19 %), 4th East/West South Central (Region 4; 274,282, 16 %), and 5th East/West North Central (Region 2; 262,088, 16 %). However, considering underlying populations, distribution and ranking appear to be different, displaying a smaller variance in surgical demand. Further, the number of surgeons and rate of procedures show great regional variation. CONCLUSIONS: Demand for plastic surgery is influenced by patients' geographic background and varies among U.S. regions. While ASPS data provide important information, additional insight regarding the demand for surgical procedures can be gained by taking certain demographic factors into consideration. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26883972 TI - An in-situ synthesis of Ag/AgCl/TiO2/hierarchical porous magnesian material and its photocatalytic performance. AB - The absorption ability and photocatalytic activity of photocatalytic materials play important roles in improving the pollutants removal effects. Herein, we reported a new kind of photocatalytic material, which was synthesized by simultaneously designing hierarchical porous magnesian (PM) substrate and TiO2 catalyst modification. Particularly, PM substrate could be facilely prepared by controlling its crystal phase (Phase 5, Mg3Cl(OH)5 . 4H2O), while Ag/AgCl particles modification of TiO2 could be achieved by in situ ion exchange between Ag(+) and above crystal Phase. Physiochemical analysis shows that Ag/AgCl/TiO2/PM material has higher visible and ultraviolet light absorption response, and excellent gas absorption performance compared to other controls. These suggested that Ag/AgCl/TiO2/PM material could produce more efficient photocatalytic effects. Its photocatalytic reaction rate was 5.21 and 30.57 times higher than that of TiO2/PM and TiO2/imporous magnesian substrate, respectively. Thus, this material and its intergration synthesis method could provide a novel strategy for high-efficiency application and modification of TiO2 photocatalyst in engineering filed. PMID- 26883973 TI - beta-caryophyllene, a dietary cannabinoid, complexed with beta-cyclodextrin produced anti-hyperalgesic effect involving the inhibition of Fos expression in superficial dorsal horn. AB - AIMS: Evaluate the anti-hyperalgesic effect of the complex containing beta caryophyllene (betaCP) and beta-cyclodextrin (betaCD) in a non-inflammatory chronic muscle pain mice model and investigated its action on superficial dorsal horn of the lumbar spinal cord. MAIN METHODS: The betaCP-betaCD complex were prepared and characterized through the DSC, TG/DTG, FTIR, XRD and SEM. The model of chronic muscle pain was induced by two injections of pH4.0 saline (20MUL) into left gastrocnemius 5days apart. After confirming hyperalgesia, male mice were treated with betaCP-betaCD (10 or 20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) daily for 9days. 1h after, the mechanical hyperalgesia, muscle withdrawal thresholds and motor performance were evaluated. To evaluate the betaCP-betaCD action on spinal cord, animals induced with chronic muscle pain were treated with betaCP-betaCD (20mg/kg; p.o.) or vehicle (saline 0.9%, p.o.) and 90min. after, were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein. KEY FINDINGS: The characterization tests indicated that betaCP were efficiently incorporated into betaCD. The oral treatment with betaCP-betaCD, at all doses tested, produced a significant (p<0.05) reduction on mechanical hyperalgesia and a significant (p<0.05) increase in muscle withdrawal thresholds, without produce any alteration in force. In addition, betaCP-betaCD was able to significantly (p<0.05) decrease Fos expression in the superficial dorsal horn. SIGNIFICANCE: Thus, betaCP-betaCD attenuates the non-inflammatory chronic muscle pain in mice and inhibits the Fos expression in the lumbar spinal cord. PMID- 26883974 TI - Relationship of endothelin-1 and NLRP3 inflammasome activation in HT22 hippocampal cells in diabetes. AB - Diabetes increases the risk and worsens the progression of cognitive decline. Diabetic rats treated with the dual endothelin receptor antagonist bosentan, have been shown to improve hippocampal-based cognitive deficits. The NLRP3 inflammasome has been implicated in vascular complications of diabetes. We hypothesized that diabetes-mediated increase in endothelin-1 (ET-1) in hippocampal cells causes NLRP3 activation and inflammation. An in vitro model was employed by exposing HT22 hippocampal cells to normal (25mM), low (5.5mM) and high (50mM) glucose conditions with and without palmitate (200MUM) in the presence and absence of 10MUM bosentan for 24h. NLRP3 activity was measured by western blotting for cryopyrin and caspase-1. ET-1 and IL-1beta expression was determined by ELISA. HT22 cells synthesize high levels of ET-1 in normal conditions, which was reduced with palmitate and bosentan as well as low and high glucose conditions. Decreased ET-1 levels were associated with greater activation of NLRP3 and IL-1beta in normal glucose. High glucose increased NLRP3 markers and activation compared to normal and low glucose. These data suggest that ET-1 may be protective to neurons. Although endothelin antagonism may be beneficial in improving vascular dysfunction and cognitive impairment, its impact on hippocampal neurons should be further explored. PMID- 26883975 TI - Biocompatible arsenic trioxide nanoparticles induce cell cycle arrest by p21(WAF1/CIP1) expression via epigenetic remodeling in LNCaP and PC3 cell lines. AB - AIMS: Arsenic trioxide (As2O3) is a well-known anticancer drug and is approved by the FDA for its use in acute promyelocytic leukemia. In this study, anticancer and antiproliferative mechanism of biocompatible As2O3 nanoparticles was determined on human prostate cancer cell lines. MAIN METHODS: In vitro anticancer efficacy of biopolymer coated As2O3 NPs was investigated in LNCaP and PC-3 cell lines, by assessing DNA damage, changes in epigenetic modulations, expression level of apoptotic markers and cell cycle analysis following treatment with As2O3 NPs. KEY FINDINGS: Our results demonstrate that the nanoparticulate formulation of dimercaptosuccinic acid (DMSA) and chitosan coated As2O3 is capable of inducing morphological changes, DNA damage and caspase-dependent apoptosis along with the expression of cyclin-dependent kinase inhibitor p21 by upregulation of Bax and downregulation of Bcl-2 and Bcl-xL proteins. The expression of cyclin dependent kinase inhibitor - p21 was found to be triggered by changes in epigenetic modifications at histone tails. SIGNIFICANCE: Biopolymer coated As2O3 nanoparticles induced reversal of mono, di and tri-methylation of histone H3 at lysine 9 residue. Acetylation of histone H3 at lysine 14 residue and phosphorylation of H3 at serine 10 residue synergistically activated p21(WAF1/CIP1) gene thereby leading to apoptosis in the LNCaP and PC-3 cells. Treatment with As2O3 nanoparticles arrested the cells in G0-G1 and G2-M phase of cell cycle in LNCaP and PC-3 cells respectively. Thus, biocompatible As2O3 nanoparticles with reduced toxicity to normal cells but the antiproliferative effect on prostate cancer cell lines follow similar death pathway as that of bare As2O3 nanoparticles. PMID- 26883977 TI - Systematic understanding of acute effects of intravenous guanfacine on rat carotid sinus baroreflex-mediated sympathetic arterial pressure regulation. AB - AIMS: To assess the acute effects of intravenous guanfacine, an alpha2A adrenergic agonist, on sympathetic outflow from the central nervous system and on sympathetic arterial pressure (AP) response. MAIN METHODS: In anesthetized Wistar Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in electrical sympathetic nerve activity (SNA) and AP in response to a baroreceptor pressure input were examined before and after an intravenous administration of a high dose (100MUg/kg, n=7) or a low dose (20MUg/kg, n=5) of guanfacine. KEY FINDINGS: The higher dose of guanfacine significantly narrowed the range of the AP response (86.8+/-6.4 to 38.4+/-12.9mmHg, P<0.01) but increased the minimum AP (79.3+/-7.5 to 93.2+/-8.7mmHg, P<0.05). In the neural arc, guanfacine reduced both the response range (90.4+/-2.3 to 33.4+/-10.7%, P<0.01) and the minimum SNA (11.4+/-1.9 to 2.6+/-1.5%, P<0.01). In the peripheral arc, guanfacine increased the intercept (67.6+/-7.1 to 92.8+/-8.5mmHg, P<0.01) without a significant effect on the slope. The lower dose of guanfacine weakened the effects on both the neural and peripheral arcs. SIGNIFICANCE: Guanfacine suppressed SNA without a significant reduction of AP, which may be attributable to the peripheral vasoconstrictive effect. Reducing the dose of acutely administered intravenous guanfacine does not aid in separating the central sympathoinhibitory effect from the peripheral vasoconstrictive effect on AP in anesthetized rats in vivo. PMID- 26883976 TI - Antinociceptive effect and mechanism of action of isatin, N-methyl isatin and oxopropyl isatin in mice. AB - AIMS: There has been growing interest in the synthesis of new derivatives from isatin, found in Isatis genus. Our objectives were to characterize the antinociceptive mechanism of action of isatin, N-methyl-isatin (MI) and N-methyl 3-(2-oxopropyl)-3-hydroxy-2-oxindole (MOI). MATERIALS AND METHODS: Substances (0.1-10mg/kg, p.o.) were studied in chemical (paw licking induced by formalin, capsaicin or glutamate) or thermal (hot plate) models of nociception. The involvement of several systems was evaluated using different receptor antagonists. KEY FINDINGS: All three substances inhibit both phases of formalin induced licking, increase the area under the curve and MI and MOI have a higher effect than that of morphine (in hot plate). Capsaicin and glutamate-induced licking were also reduced by all three substances. In the hot plate model, the antinociceptive effect of isatin was reduced by naloxone and atropine; naloxone, atropine and L-NAME reduced MI effect while naloxone, atropine, L-NAME, mecamylamine and ondansetron reduced MOI effect. SIGNIFICANCE: Our results suggest that isatin, MI and MOI: 1) present activity in models of nociception; 2) capsaicin and glutamate receptors seems to participate in the mechanism of action; 3) opioid, cholinergic, serotoninergic, nitrergic and adrenergic systems may be involved, at least in part, in the mechanism of action of some of these substances. PMID- 26883978 TI - Anti-diabetes effect of chronic intermittent hypobaric hypoxia through improving liver insulin resistance in diabetic rats. AB - AIM: Cumulating evidence demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had beneficial effects on the body. The present study was to investigate the anti-diabetes effect of CIHH in type-2 diabetic rats for the first time. MAIN METHODS: Sprague-Dawley rats were randomly divided into 4 groups: control group (CON), diabetes mellitus group (DM, induced by high-fat diet combined with low dose streptozotocin), CIHH treatment group (CIHH, simulated 5000-m altitude, 6h per day for 28 days), and diabetes mellitus plus CIHH treatment group (DM+CIHH). Histopathology of liver, systolic arterial blood pressure (SAP), blood biochemicals, glucose and insulin tolerance were determined. The expression of proteins associated with insulin signaling pathway as well as hypoxia induced factors were assayed. KEY FINDINGS: Diabetic rats showed impaired glucose tolerance, dyslipidemia, hepatic steatosis and hepatic insulin resistance in addition to increased SAP. However, SAP, serum triglyceride and cholesterol were decreased, and hepatic steatosis and insulin resistance were improved in DM+CIHH rats. Furthermore, the protein expression of glucokinase (GCK), insulin receptor substrates (IRS-1 and IRS-2), and HIF1alpha were increased, while the expression of phosphoenolpyruvate carboxykinase (PEPCK), was markedly reduced in DM+CIHH rats. SIGNIFICANCE: We conclude that CIHH treatment has anti-diabetes effects through ameliorating insulin resistance via hepatic HIF-insulin signaling pathway in type-2 diabetic rats. PMID- 26883979 TI - Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats. AB - Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. PMID- 26883980 TI - Gossypol ameliorates liver fibrosis in diabetic rats induced by high-fat diet and streptozocin. AB - 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) inhibitors have been shown to treat type 2 diabetes (T2D). Since gossypol is an 11beta-HSD1 inhibitor, the objective of the present study was to treat T2D and T2D-related liver fibrosis in rat model using low-dose gossypol. T2D was induced by feeding with high fat diet plus injection of streptozocin (30mg/kg). Diabetic rats were treated with either vehicle control or racemic gossypol with a dose of 15mg/kg/day for 4weeks followed by 15mg/kg/week for additional 8weeks. Blood glucose, cholesterol, LDL, and triglycerides were measured. Messenger mRNA levels of glucocorticoid receptor (Nr3c1), phosphoenolpyruvate carboxykinase (Pck1), glucose-6-phosphatase (G6pc), collagen I (Col1a1), collagen III (Col3a1), fibronectin (Fn1), tissue inhibitor of metalloproteinase 1 (Timp1), and 2 (Timp2) were measured. T2D rats had higher serum glucose, cholesterol, LDL, and triglyceride levels compared to control. Liver Nr3c1, Col1a1, Col3a1, Fn1, Timp1, and Timp2 were increased in T2D rats. T2D liver showed significant fibrosis with the increases of alpha-smooth muscle actin and fibronectin. After gossypol treatment, serum glucose level was lowered by 64%. Liver fibrosis was significantly ameliorated. Nr3c1, Col1a1, Col3a1, Fn1, Timp1, Timp2, Pck1 as well as G6pc levels were significantly reduced. In conclusion, low dose gossypol is effective for the treatment of T2D and T2D related fibrosis. PMID- 26883981 TI - The best of two worlds: a new innovative laparoscopic Rives-Stoppa technique for ventral/incisional hernias--"the Brazilian technique": Invited commentary to: Transabdominal midline reconstruction by minimally invasive surgery: technique and results. Costa TN, Abdalla RZ, Santo MA, Tavares RRFM, Abdalla BMZ, Cecconello I. PMID- 26883982 TI - Quantitative analysis of high plasma lactate concentration in ED patients after alcohol intake. AB - INTRODUCTION: Plasma lactate concentration is known to increase after alcohol intake. However, this increase has rarely been analyzed quantitatively in emergency department (ED) settings. Evaluating plasma lactate elevation in ED patients after alcohol intake is important because it can affect patients' evaluation based on the plasma lactate level. METHODS: This study analyzed venous lactate concentrations of 196 continuous patients presented to our ED after alcohol intake. The control group comprised 219 successive ED patients without alcohol intake. Patients who had conditions that might induce lactate elevation were excluded from both groups. RESULTS: Venous lactate concentration was significantly higher in the alcohol intake group (2.83 mmol/L; 95% confidence interval, 2.69-2.96 mmol/L) than in the control group (1.65 mmol/L; 95% confidence interval, 1.53-1.77 mmol/L; P<.05). Lactate concentrations exceeding 3 mmol/L and exceeding 4 mmol/L were found, respectively, in 41.8% and 12.2% of the alcohol intake group compared with in 8.7% and 2.3% of the control group (P<.05). Lactate concentrations do not correlate with patients' level of consciousness. Therefore, a higher plasma ethanol level is apparently unrelated to elevated lactate. DISCUSSION AND CONCLUSION: Analyses show that plasma lactate concentration is significantly higher in ED patients after alcohol intake and to a greater degree than previously reported, even in patients without previously known alcohol-related diseases. Emergency department physicians must be careful when interpreting the lactate level of the patients with alcohol intake. PMID- 26883983 TI - Tidal pumping facilitates dissimilatory nitrate reduction in intertidal marshes. AB - Intertidal marshes are alternately exposed and submerged due to periodic ebb and flood tides. The tidal cycle is important in controlling the biogeochemical processes of these ecosystems. Intertidal sediments are important hotspots of dissimilatory nitrate reduction and interacting nitrogen cycling microorganisms, but the effect of tides on dissimilatory nitrate reduction, including denitrification, anaerobic ammonium oxidation and dissimilatory nitrate reduction to ammonium, remains unexplored in these habitats. Here, we use isotope-tracing and molecular approaches simultaneously to show that both nitrate-reduction activities and associated functional bacterial abundances are enhanced at the sediment-tidal water interface and at the tide-induced groundwater fluctuating layer. This pattern suggests that tidal pumping may sustain dissimilatory nitrate reduction in intertidal zones. The tidal effect is supported further by nutrient profiles, fluctuations in nitrogen components over flood-ebb tidal cycles, and tidal simulation experiments. This study demonstrates the importance of tides in regulating the dynamics of dissimilatory nitrate-reducing pathways and thus provides new insights into the biogeochemical cycles of nitrogen and other elements in intertidal marshes. PMID- 26883984 TI - Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain. AB - Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4 degrees C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4 degrees C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke. PMID- 26883987 TI - Correction: Water on Au sputtered films. PMID- 26883986 TI - The physico-chemical properties and structural characteristics of artificial soil for cut slope restoration in Southwestern China. AB - Cut slopes are frequently generated by construction work in hilly areas, and artificial soil is often sprayed onto them to promote ecological rehabilitation. The artificial soil properties are very important for effective management of the slopes. This paper uses fractal and moment methods to characterize soil particle size distribution (PSD) and aggregates composition. The fractal dimension (D) showed linear relationships between clay, silt, and sand contents, with coefficients of determination from 0.843 to 0.875, suggesting that using of D to evaluate the PSD of artificial soils is reasonable. The bias (CS) and peak convex (CE) coefficients showed significant correlations with structure failure rate, moisture content, and total porosity, which validated the moment method to quantitatively describe soil structure. Railway slope (RS) soil has lower organic carbon and soil moisture, and higher pH than natural slope soil. Overall, RS exhibited poor soil structure and physicochemical properties, increasing the risk of soil erosion. Hence, more effective management measures should be adopted to promote the restoration of cut slopes. PMID- 26883985 TI - Integrated GlycoProteome Analyzer (I-GPA) for Automated Identification and Quantitation of Site-Specific N-Glycosylation. AB - Human glycoproteins exhibit enormous heterogeneity at each N-glycosite, but few studies have attempted to globally characterize the site-specific structural features. We have developed Integrated GlycoProteome Analyzer (I-GPA) including mapping system for complex N-glycoproteomes, which combines methods for tandem mass spectrometry with a database search and algorithmic suite. Using an N glycopeptide database that we constructed, we created novel scoring algorithms with decoy glycopeptides, where 95 N-glycopeptides from standard alpha1-acid glycoprotein were identified with 0% false positives, giving the same results as manual validation. Additionally automated label-free quantitation method was first developed that utilizes the combined intensity of top three isotope peaks at three highest MS spectral points. The efficiency of I-GPA was demonstrated by automatically identifying 619 site-specific N-glycopeptides with FDR <= 1%, and simultaneously quantifying 598 N-glycopeptides, from human plasma samples that are known to contain highly glycosylated proteins. Thus, I-GPA platform could make a major breakthrough in high-throughput mapping of complex N-glycoproteomes, which can be applied to biomarker discovery and ongoing global human proteome project. PMID- 26883988 TI - Photophysics of Hybrid Lead Halide Perovskites: The Role of Microstructure. AB - Since the first reports on high efficiency, solution processed solar cells based on hybrid lead halide perovskites, there has been an explosion of activities on these materials. Researchers with interests spanning the full range from conventional inorganic to emerging organic and hybrid optoelectronic technologies have been contributing to the prolific research output. This has led to solar cell power conversion efficiencies now exceeding 20% and the demonstration of proofs of concept for electroluminescent and lasing devices. Hybrid perovskites can be self-assembled by a simple chemical deposition of the constituent units, with the possibility of integrating the useful properties of organic and inorganic compounds at the molecular scale within a single crystalline material, thus enabling a fine-tuning of the electronic properties. Tellingly, the fundamental properties of these materials may make us think of a new, solution processable, GaAs-like semiconductor. While this can be true to a first approximation, hybrid perovskites are intrinsically complex materials, where the presence of various types of interactions and structural disorder may strongly affect their properties. In particular, a clear understanding and control of the relative interactions between the organic and inorganic moieties is of paramount importance to properly disentangle their innate physics. In this Account we review our recent studies which aim to clarify the relationship between structural and electronic properties from a molecular to mesoscopic level. First we identify the markers for local disorder at the molecular level by using Raman spectroscopy as a probe. Then, we exploit such a tool to explore the role of microstructure on the absorption and luminescence properties of the semiconductor. Finally we address the controversy surrounding electron-hole interactions and excitonic effects. We show that in hybrid lead-halide perovskites dielectric screening also depends on the local microstructure of the hybrid crystals and not only on its chemical composition. This leads to the possibility of band gap engineering and the consequent control of the elementary photoexcitation dynamics that determine the perovskites' performances in different optoelectronic devices. PMID- 26883991 TI - [Triage: ESI or Manchester Triage?]. PMID- 26883992 TI - Ion-shaping of embedded gold hollow nanoshells into vertically aligned prolate morphologies. AB - Ion beam shaping is a novel technique with which one can shape nano-structures that are embedded in a matrix, while simultaneously imposing their orientation in space. In this work, we demonstrate that the ion-shaping technique can be implemented successfully to engineer the morphology of hollow metallic spherical particles embedded within a silica matrix. The outer diameter of these particles ranges between 20 and 60 nm and their shell thickness between 3 and 14 nm. Samples have been irradiated with 74 MeV Kr ions at room temperature and for increasing fluences up to 3.8 * 10(14) cm(-2). In parallel, the experimental results have been theoretically simulated by using a three-dimensional code based on the thermal-spike model. These calculations show that the particles undergo a partial melting during the ion impact, and that the amount of molten phase is maximal when the impact is off-center, hitting only one hemisphere of the hollow nano-particle. We suggest a deformation scenario which differs from the one that is generally proposed for solid nano-particles. Finally, these functional materials can be seen as building blocks for the fabrication of nanodevices with really three-dimensional architecture. PMID- 26883990 TI - Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. AB - Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade. PMID- 26883994 TI - New law on staffing levels will save lives. AB - Good news about nurse staffing levels can be hard to find, so how fantastic that a protracted campaign in Wales finally paid off last week with the passage of legislation to ensure hospital wards are staffed safely. Next month, the Queen will give royal assent to the Safe Nurse Staffing Levels (Wales) Bill, which will save lives, produce better outcomes and enhance the patient experience of care. PMID- 26883995 TI - Treatment of junior doctors is the thin end of the wedge, warn unions. AB - Nurse unions fear the decision to force junior doctors to accept a new contract could lead to their members experiencing a similar fate. PMID- 26883993 TI - Reliability and validity of the Swedish Fatigue Assessment Scale when self administrered by persons with mild to moderate stroke. AB - OBJECTIVE: To examine internal consistency, test-retest reliability, floor/ceiling effects and construct validity of the Fatigue Assessment Scale (FAS), when self-administrated by persons with mild to moderate stroke. METHOD: The FAS was translated into Swedish and tested for psychometric properties when self-administrated by persons with mild to moderate stroke. Participants, consequently selected from the stroke unit admission register received a letter with three questionnaires: the FAS, Short Form Health Survey (SF-36) subscale for vitality and Geriatric Depression Scale, GDS-15. Within two weeks, a second letter with FAS was sent for re-test. RESULT: Seventy-tree persons with mild to moderate stroke participated in the study. Internal consistency was good (Cronbach's alpha 0.82). The test and retest reliability of individual items showed that five items out of 10 items were good (weighted kappa > 0.60), four were moderate (0.40-0.60), and one was fair (0.22). The relative reliability between total scores was good (ICC 3.1 = 0.73) and the absolute reliability was nine points, meaning that a change of at least nine points in total score implies a real change of fatigue level. Correlation analysis showed that the Swedish FAS correlated with the SF-36 subscale for vitality (rs = - 0.73) and GDS-15 (rs = 0.62), suggesting convergent construct validity. There were no floor or ceiling effects. CONCLUSION: The Swedish translation of the FAS used as a self administrated questionnaire is reliable and valid for measuring fatigue in persons with mild to moderate stroke. PMID- 26883996 TI - Student voices heard in a week of protests. AB - Protests by nursing students about the potential loss of the NHS bursary have been hailed a success despite poor turnout for some events. PMID- 26883997 TI - Attitude survey shows growing public disquiet at NHS staffing and wait times. AB - Staff shortages are the second most common reason for dissatisfaction with the NHS, a survey found. PMID- 26883998 TI - Welsh lead the way with approval of staffing levels bill. AB - Wales is to become the first country in the UK to mandate nurse staffing in its hospitals. PMID- 26883999 TI - Nurse shortage linked to higher neonatal mortality. AB - A fall in one-to-one nursing care of sick and premature babies is being linked to increased death rates. PMID- 26884000 TI - Gay 'cure', a sobering lesson for all. AB - The ways that mental health nurses used to administer 'cures' for homosexuality have been outlined at an RCN lecture. PMID- 26884001 TI - Death rates show patients pay the price for over-reliance on HCSWs. AB - Hospitals with higher nurse to patient ratios have lower death rates, according to a study led by the University of Southampton and King's College London. PMID- 26884002 TI - Mental health task force says investment in nurses is vital. AB - A group of experts set up to advise on an overhaul of mental health services say nurse training and staffing levels must improve. PMID- 26884003 TI - Psychological help vital for myeloma. AB - Patients with myeloma should be offered psychological assessment and support at various stages in their treatment, according to guidance from the National Institute for Health and Care Excellence. PMID- 26884005 TI - NICE says infection control should be the responsibility of all staff. AB - Nurses could be set objectives to ensure all staff entering their ward follow infection control procedures, a nurse consultant has suggested. PMID- 26884006 TI - Staff vow to help patients marry in style. AB - A ward sister and her colleagues want to create 'wedding boxes' for patients getting married at short notice. PMID- 26884013 TI - Colorectal cancer. AB - Essential facts Colorectal cancer is the fourth most common cancer in the UK, after breast, lung and prostate cancer, with around 41,600 people in the UK diagnosed each year. It is the second most common cause of cancer death in the UK. According to the charity Bowel Cancer UK, 98% of people diagnosed at the earliest stage will survive, while less than 10% of those diagnosed at the latest stage will survive more than five years. PMID- 26884007 TI - Lord Carter's model hospitals aim to save the NHS L5 billion a year. AB - A lack of standardised procedures in the use of resources across acute hospitals is costing the NHS billions, according to Labour peer Lord Carter of Coles. PMID- 26884014 TI - Break down the barriers. PMID- 26884015 TI - Vanguards: support for care home staff. PMID- 26884027 TI - The best of the week's health-related TV and radio. PMID- 26884016 TI - The safety net with too many holes in it. PMID- 26884028 TI - Clinic Finder app. AB - Refugees seeking medical care can access information on primary healthcare and medical services across Europe with the Clinic Finder app. PMID- 26884029 TI - Creating the nursing associate role is a waste of time and money. AB - There has been a lot of talk about the new 'nursing associate' role Health Education England (HEE) is looking to create. PMID- 26884030 TI - New job title blurs boundaries and will confuse the public. AB - In response to the consultation on the introduction of a nursing associate role (News, February 3), I believe it is ill-advised to include the word 'nurse' in the title, because this necessitates the involvement of the nursing regulator, and will therefore incur costs. PMID- 26884032 TI - Be part of a book on the 1950s and 1960s and share royalties. AB - I've been asked by a major UK publisher to write a book based on the life of a nurse who worked - perhaps as a district nurse - for some or all of the 1950s and 1960s. I have written similar books, including The Maid's Tale. PMID- 26884031 TI - Voice of support needs to be heard over the voice of abuse. AB - I would like to respond to comments on the difficulties associated with disclosing domestic abuse (Letters, February 3). Domestic abuse is one of the most complex relationships a person can find themselves in. Its effects infiltrate every sector of life like a disease with no barriers, leaving the person increasingly weak and broken. It also leaves scars years after the bruises have gone and broken bones have healed. PMID- 26884034 TI - Correction. AB - In the On the Move column in our February 10 issue we said that Abigail Masterson has been appointed chief executive of the Florence Nightingale Foundation. In fact she is deputy chief executive. We also described her as a former nurse, but Ms Masterson remains on the professional register. We apologise for the error. PMID- 26884035 TI - Mental health nursing is stretched to breaking point. AB - The report on mental health nurse shortages (News, February 3) shows just how much pressure staff are under. PMID- 26884036 TI - Bring back the pool! In the long run, it will save the NHS money. AB - I was interested to read Donato Tallo's comments about ways of avoiding dependence on expensive nursing agencies (Letters, February 10). PMID- 26884040 TI - The importance of spirituality for people living with dementia. AB - Spiritual care is an essential aspect of caring for people with dementia. It can improve their quality of life and give them the strength to cope with living with their condition. However, spirituality is a poorly understood concept and healthcare practitioners often lack confidence in assessing and meeting spiritual needs. Therefore, the spiritual needs of people with dementia are often overlooked, which can result in spiritual distress. This article provides an overview of spirituality and spiritual needs. It discusses the potential causes of spiritual distress in people with dementia and provides examples of spiritual care strategies. PMID- 26884039 TI - How to repair an episiotomy. AB - Rationale and key points Skilful repair of an episiotomy is an important aspect of maternal health care. It is essential that midwives and doctors have the knowledge and skills to undertake this procedure in a safe and effective manner. ? An episiotomy should be repaired promptly to reduce blood loss and prevent infection. ? Repair of an episiotomy is undertaken in three stages: repair of the vaginal mucosa, repair of the muscle layer and repair of the skin layer. ? Adequate pain relief should be provided before suturing. Reflective activity Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. Why a rectal examination is recommended before and following repair of an episiotomy. 2. What you would do to improve your suturing skills. 3. The factors that may prevent or delay an episiotomy from healing. Subscribers can upload their reflective accounts at rcni.com/portfolio . PMID- 26884041 TI - Infusion-related risks associated with chemotherapy. AB - This article provides a comprehensive overview of the risks associated with the administration of chemotherapy, monoclonal antibodies and targeted or biological therapies in the management of solid tumours. The main physiological actions of these agents are discussed, with reference to the immediate infusion-related side effects and complications that may arise from an extravasation injury. The article focuses on the identification and early recognition of these risk factors to implement preventive measures and appropriate management strategies. PMID- 26884042 TI - Preventing amputation. AB - Many adults with diabetes experience complications as a result of sub-optimal management of the disease. One of the complications is foot ulceration, which can lead to amputation if left untreated. PMID- 26884043 TI - Networking benefits. AB - Making time for networking should be an essential part of every nurse's career. As well as helping you get ahead professionally, it enables you to share expertise and best practice with colleagues and provide emotional support for one other. PMID- 26884045 TI - Rewarding work in sexual health. AB - As part of her day-to-day job, Robyn Connelly is a nurse, counsellor, women's advocate, safeguarder, social worker and dispenser of many tissues. PMID- 26884046 TI - Student life - Powerful at every level. AB - Working with a group of nursing students one day, I discussed with them communication skills when caring for people with cognitive impairment, dementia and delirium. PMID- 26884047 TI - Appropriate assessment of ethnic differences in adolescent use of psychotropic medication: multilevel analysis of discriminatory accuracy. AB - OBJECTIVE: In the present study, we used a multilevel approach to investigate the role of maternal country of birth (MCOB) in predicting adolescent use of psychotropic medication in Sweden. DESIGN: Using the Swedish Medical Birth Register we identified all 428,314 adolescents born between 1987 and 1990 and who were residing in Sweden in the year they turned 18. We applied multilevel logistic regression analysis with adolescents (level 1) nested within MCOBs (level 2). Measures of association (odds ratio) and measures of variance (intra class correlation (ICC)) were calculated, as well as the discriminatory accuracy by calculating the area under the Receiver Operator Characteristic (AU-ROC) curve. RESULTS: In comparison with adolescents with Swedish-born mothers, adolescents with mothers born in upper-middle, lower-middle and low-income countries were less likely to use psychotropic medication. However, the variance between MCOBs was small (ICC = 2.5 in the final model) relative to the variation within MCOBs. This was confirmed by an AU-ROC value of 0.598. CONCLUSIONS: Even though we found associations between MCOB and adolescent use of psychotropic medication, the small ICC and AU-ROC indicate that MCOB appears to be an inaccurate context for discriminating adolescent use of psychotropic medication in Sweden. PMID- 26884050 TI - Setting new standards for epidemiological research on mesothelioma. PMID- 26884049 TI - Self-guided internet-based and mobile-based stress management for employees: results of a randomised controlled trial. AB - OBJECTIVE: This randomised controlled trial (RCT) aimed to evaluate the efficacy of a self-guided internet-based stress management intervention (iSMI) for employees compared to a 6-month wait-list control group (WLC) with full access for both groups to treatment as usual. METHOD: A sample of 264 employees with elevated symptoms of perceived stress (Perceived Stress Scale, PSS-10 >=22) was randomly assigned to either the iSMI or to the WLC. The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques. Self-report data were assessed at baseline, at 7 weeks and at 6 months following randomisation. The primary outcome was perceived stress (PSS 10). The secondary outcomes included other relevant mental-related and work related health outcomes. Data were analysed based on intention-to-treat principles. RESULTS: The iSMI participants showed a significantly higher reduction in perceived stress from baseline to post-treatment at 7 weeks (d=0.96, 95% CI 0.70 to 1.21) and to the 6-month follow-up (d=0.65, 95% CI 0.40 to 0.89) compared to the WLC. Significant differences with small to moderate effect sizes were also found for depression, anxiety, emotional exhaustion, sleeping problems, worrying, mental health-related quality of life, psychological detachment, emotion regulation skills and presenteeism, in favour of the experimental group. At the 6 -month follow-up, all outcomes remained significantly better for the experimental group with the exception of work engagement, physical health-related quality of life and absenteeism, which were not found to significantly differ between the iSMI and WLC groups. CONCLUSIONS: The iSMI investigated in this study was found to be effective in reducing typical mental-related and work-related health symptoms of stressed employees. Internet-based self-guided interventions could be an acceptable, effective and potentially cost-effective approach to reduce the negative consequences associated with work-related stress. PMID- 26884048 TI - Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK. AB - OBJECTIVES: There is evidence of adverse associations between short-term exposure to traffic-related pollution and health, but little is known about the relative contribution of the various sources and particulate constituents. METHODS: For each day for 2011-2012 in London, UK over 100 air pollutant metrics were assembled using monitors, modelling and chemical analyses. We selected a priori metrics indicative of traffic sources: general traffic, petrol exhaust, diesel exhaust and non-exhaust (mineral dust, brake and tyre wear). Using Poisson regression models, controlling for time-varying confounders, we derived effect estimates for cardiovascular and respiratory hospital admissions at prespecified lags and evaluated the sensitivity of estimates to multipollutant modelling and effect modification by season. RESULTS: For single day exposure, we found consistent associations between adult (15-64 years) cardiovascular and paediatric (0-14 years) respiratory admissions with elemental and black carbon (EC/BC), ranging from 0.56% to 1.65% increase per IQR change, and to a lesser degree with carbon monoxide (CO) and aluminium (Al). The average of past 7 days EC/BC exposure was associated with elderly (65+ years) cardiovascular admissions. Indicated associations were higher during the warm period of the year. Although effect estimates were sensitive to the adjustment for other pollutants they remained consistent in direction, indicating independence of associations from different sources, especially between diesel and petrol engines, as well as mineral dust. CONCLUSIONS: Our results suggest that exhaust related pollutants are associated with increased numbers of adult cardiovascular and paediatric respiratory hospitalisations. More extensive monitoring in urban centres is required to further elucidate the associations. PMID- 26884051 TI - 99mTc-MIBI scintigraphy in the diagnosis of multiple myeloma. PMID- 26884053 TI - What are patients' expectations of orthodontic treatment: a systematic review. AB - BACKGROUND: What patients expect to happen during treatment or benefit from the treatment might influence the subsequent factors such as treatment outcome, patient satisfaction, patient's cooperation as well as compliance. The aim of this systematic review is to assess the role of patients' expectations from orthodontic treatment. METHODS: A systematic literature search of four databases Pubmed, Cochrane, Web of Science and PsychINFO was conducted following PRISMA guidelines. Studies reporting expectations regarding orthodontic treatment were selected and a narrative review was conducted. The quality of study was rated according to STROBE statements and the methodology as well as key findings were summarized. RESULTS: Thirteen studies (14 papers) were finally included for analysis. Among them, only one was a randomized control trial, while the rest included one cohort study, two questionnaire-developments and ten cross-sectional studies. The STROBE quality of reporting scores of the studies ranged from 12 to 18. Seven papers described expectations of the treatment experiences, along with seven talking about benefit expectations from the treatment. Dental appearance and function improvement were most expected in studies relate to the treatment benefits. CONCLUSIONS: Orthodontics appears to have adopted various standardized questionnaires. However, most of them are poor in the quality of methodology and results analyses, which prohibit synthesizing sufficient evidence to help identify which factors influence patient expectations. The evidence of "expectations" affecting treatment outcomes is not found in current research. Future studies are needed to better understand the impact of "expectation" on the treatment both theoretically and experimentally. PMID- 26884052 TI - The relationship between atmospheric lead emissions and aggressive crime: an ecological study. AB - BACKGROUND: Many populations have been exposed to environmental lead from paint, petrol, and mining and smelting operations. Lead is toxic to humans and there is emerging evidence linking childhood exposure with later life antisocial behaviors, including delinquency and crime. This study tested the hypothesis that childhood lead exposure in select Australian populations is related to subsequent aggressive criminal behaviors. METHODS: We conducted regression analyses at suburb, state and national levels using multiple analytic methods and data sources. At the suburb-level, we examined assault rates as a function of air lead concentrations 15-24 years earlier, reflecting the ubiquitous age-related peak in criminal activity. Mixed model analyses were conducted with and without socio demographic covariates. The incidence of fraud was compared for discriminant validity. State and national analyses were conducted for convergent validity, utilizing deaths by assault as a function of petrol lead emissions. RESULTS: Suburb-level mixed model analyses showed air lead concentrations accounted for 29.8 % of the variance in assault rates 21 years later, after adjusting for socio demographic covariates. State level analyses produced comparable results. Lead petrol emissions in the two most populous states accounted for 34.6 and 32.6 % of the variance in death by assault rates 18 years later. CONCLUSIONS: The strong positive relationship between childhood lead exposure and subsequent rates of aggressive crime has important implications for public health globally. Measures need to be taken to ameliorate exposure to lead and other environmental contaminants with known neurodevelopmental consequences. PMID- 26884054 TI - Novel Vertical 3D Structure of TaOx-based RRAM with Self-localized Switching Region by Sidewall Electrode Oxidation. AB - A novel vertical 3D RRAM structure with greatly improved reliability behavior is proposed and experimentally demonstrated through basically compatible process featuring self-localized switching region by sidewall electrode oxidation. Compared with the conventional structure, due to the effective confinement of the switching region, the newly-proposed structure shows about two orders higher endurance (>10(8) without verification operation) and better retention (>180h@150 degrees C), as well as high uniformity. Corresponding model is put forward, on the base of which thorough theoretical analysis and calculations are conducted as well, demonstrating that, resulting from the physically-isolated switching from neighboring cells, the proposed structure exhibits dramatically improved reliability due to effective suppression of thermal effects and oxygen vacancies diffusion interference, indicating that this novel structure is very promising for future high density 3D RRAM application. PMID- 26884055 TI - Predictive and prognostic value of PET/CT imaging post-chemoradiotherapy and clinical decision-making consequences in locally advanced head & neck squamous cell carcinoma: a retrospective study. AB - BACKGROUND: The accuracy of (18)F-fluorodeoxygluocose positron emission tomography/computed tomography (PET/CT) in predicting immediate failure after radical chemoradiotherapy (CRT) for HNSCC is poorly characterized at present. The purpose of this study was to examine PET/CT as a predictive and prognostic gauge of immediate failure after CRT and determine the impact of these studies on clinical decision making in terms of salvage surgery. METHODS: Medical records of 78 consecutive patients receiving radical CRT for locally advanced HNSCC were reviewed, analyzing PET/CTs done before and 3 months after CRT. Immediate failure was defined as residual disease or locoregional and/or systemic relapse within 6 months after CRT. RESULTS: Maximum standard uptake value (SUV) of post CRT PET/CT (postSUVmax) was found optimal for predicting immediate failure at a cutpoint of 4.4. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 90.0%, 83.8%, 98.3%, and 45.0%, respectively. Of 78 patients studied, postSUVmax >= 4.4 prevailed in 20 (25.6%), with postSUVmax <4.4 in 58 (74.4%). At postSUVmax >= 4.4 (vs. postSUVmax <4.4) OS was poorer by comparison (3-year OS: 56.9 vs. 87.7%; P = 0.005), as was progression-free survival (3-year PFS: 42.9 vs. 81.1%; P < 0.001). At postSUVmax >= 4.4, OS with and without immediate salvage surgery did not differ significantly (3-year OS: 60.0 vs. 55.6%; Log-rank P = 0.913). CONCLUSION: Post CRT PET/CT imaging has prognostic value in terms of OS and PFS and is useful in predicting immediate therapeutic failure, given its high NPV. However, OS was not significantly altered by early salvage surgery done on the basis of post CRT PET/CT findings. PMID- 26884056 TI - Cellular Uptake and Intra-Organ Biodistribution of Functionalized Silica-Coated Gold Nanorods. AB - PURPOSE: To develop a new nanobiosystem based on folate-functionalized silica coated gold nanorods and to investigate its cellular uptake and intra-organ biodistribution in vitro and in vivo. PROCEDURES: Ellipsoidal silica-coated gold nanorods (GNRs@SIO2) were prepared by seeded growth method using silicon dioxide (SIO2) as the shell material. Rhodamine-labeled GNRs@SiO2-folic acid (FA) were obtained by reacting the amino group located on GNRs@SiO2-FA with rhodamine isothiocyanate. The characteristics of the prepared GNRs@SiO2-FA were studied using transmission electron microscopy (TEM) and UV spectra. The 3-[4, 5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide (MTT) colorimetric method was used to assess the biocompatibility of GNRs@SiO2-FA, and their uptake into cells was observed using TEM. In vivo experiments of cellular uptake and study of the intra-organ biodistribution of GNRs@SiO2-FA were detected using intrinsic two photon luminescence. RESULTS: Analysis of UV spectra confirmed the successfu1 preparation of GNRs@SiO2-FA. Results of the MTT assay demonstrated that surface modification of GNRs@SiO2-FA resulted in excellent biocompatibility. TEM examination revealed that GNRs@SiO2-FA entered the cells via endocytosis, which could connect to cancer cells with high folic acid expression. We found that GNRs exhibit bright luminescence and could be visualized in vivo by direct imaging of these particles within the tissue. Additionally, GNRs@SiO2-FA could specifically bind to tumor cells. GNRs@SiO2-FA entered tumor cells within 24 h and had a heterogeneous distribution with higher accumulation at the tumor cytoplasm. CONCLUSION: GNRs@SiO2-FA can bind to cells and were found to be internalized by targeted folate receptor-expressing cells via a ligand-receptor-mediated endocytosis pathway, which is very useful in diagnosing diseases as well as in treating neoplasm with I-125 particles. PMID- 26884057 TI - Evaluation of Quantitative Imaging Biomarkers in the DSS Colitis Model. AB - PURPOSE: In humans, colonoscopy is the gold standard for the diagnosis of inflammatory changes of the colon wall. Aim of this study was the identification of less invasive imaging biomarkers in the dextran sodium sulfate (DSS) colitis model to provide additional information on transmural changes of the colon wall. PROCEDURES: Colitis was induced in C57BL/6 mice by administration of 2, 3, and 4 % DSS over a period of 5 days. Colon wall thickness was measured using magnetic resonance imaging (MRI), ultrasound (US), and x-ray computed tomography (CT), gut inflammation by positron emission tomography/CT, and mucosal changes of the colon wall by colonoscopy. Colon samples were examined histologically. RESULTS: MRI, CT, US, and histological data revealed increased colon wall thickness in DSS treated mice compared to healthy controls. Elevated 2-deoxy-2[(18)F]fluoro-D glucose uptake and colonoscopy confirmed high inflammatory load in the guts of colitis mice. CONCLUSIONS: The established quantitative imaging readouts offer promising perspectives to develop new compounds and to translate these methods into the clinical setting. PMID- 26884058 TI - Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI. AB - PURPOSE: An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT. PROCEDURES: All patients underwent a single 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [(18)F]FDG concentration. PET image quality was assessed by a 3-point scale (1 clinically significant artifact, 2-non clinically significant artifact, and 3-no artifact). RESULTS: Twenty-five patients (mean +/- SD age: 56 +/- 13 years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images. CONCLUSION: The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT. PMID- 26884060 TI - Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors Within the ToxCast Phase I and II Chemical Libraries. AB - High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidation assay using guaiacol as a substrate to confirm the activity profiles of putative TPO inhibitors. This effort represents the most extensive TPO inhibition screening campaign to date and illustrates a tiered screening approach that focuses resources, maximizes assay throughput, and reduces animal use. PMID- 26884061 TI - Measuring Work Engagement, Psychological Empowerment, and Organizational Citizenship Behavior Among Health Care Aides. AB - PURPOSE OF THE STUDY: Health care aides (HCAs) provide most direct care in long term care (LTC) and home and community care (HCC) settings but are understudied. We validate three key work attitude measures to better understand HCAs' work experiences: work engagement (WEng), psychological empowerment (PE), and organizational citizenship behavior (OCB-O). DESIGN AND METHODS: Data were collected from 306 HCAs working in LTC and HCC, using survey items for WEng, PE, and OCB-O adapted for HCAs. Psychometric evaluation involved confirmatory factor analysis (CFA). Predictive validity (correlations with measures of job satisfaction and turnover intention) and internal consistency reliability were examined. RESULTS: CFA supported a one-factor model of WEng, a four-factor model of PE, and a one-factor model of OCB-O. HCC workers scored higher than LTC workers on Self-determination (PE) and lower on Impact, demonstrating concurrent validity. WEng and PE correlated with worker outcomes (job satisfaction, turnover intention, and OCB-O), demonstrating predictive validity. Reliability and validity analyses indicated sound psychometric properties overall. IMPLICATIONS: Study results support psychometric properties of measures of WEng, PE, and OCB-O for HCAs. Knowledge of HCAs' work attitudes and behaviors can inform recruitment programs, incentive systems, and retention/training strategies for this vital group of care providers. PMID- 26884059 TI - Cardiac-Specific Deletion of the Pdha1 Gene Sensitizes Heart to Toxicological Actions of Ischemic Stress. AB - Pyruvate dehydrogenase (PDH) plays a key role in aerobic energy metabolism and occupies a central crossroad between glycolysis and the tricarboxylic acid cycle. We generated inducible cardiac-specific PDH E1alpha knockout (CreER(T2) PDH(flox/flox)) mice that demonstrated a high mortality rate. It was hypothesized that PDH modulating cardiac glucose metabolism is crucial for heart functions under normal physiological and/or stress conditions. The myocardial infarction was conducted by a ligation of the left anterior descending coronary arteries. Cardiac PDH E1alpha deficiency caused large myocardial infarcts size and macrophage infiltration in the hearts (P < .01 vs wild-type [WT]). Wheat germ agglutinin and Masson trichrome staining revealed significantly increased hypertrophy and fibrosis in PDH E1alpha-deficient hearts (P < .05 vs WT). Measurements of heart substrate metabolism in an ex vivo working heart perfusion system demonstrated a significant impairment of glucose oxidation in PDH E1alpha deficient hearts during ischemia/reperfusion (P < .05 vs WT). Dichloroacetate, a PDH activator, increased glucose oxidation in WT hearts during ischemia/reperfusion and reduced myocardial infarct size in WT, but not in PDH E1alpha-deficient hearts. Immunoblotting results demonstrated that cardiac PDH E1alpha deficiency leads to an impaired ischemic AMP-activated protein kinase activation through Sestrin2-liver kinase B1 interaction which is responsible for an increased susceptibility of PDH E1alpha-deficient heart to ischemic insults. Thus, cardiac PDH E1alpha deficiency impairs ischemic AMP-activated protein kinase signaling and sensitizes hearts to the toxicological actions of ischemic stress. PMID- 26884062 TI - Development and Validation of A Scheduled Shifts Staffing (ASSiST) Measure of Unit-Level Staffing in Nursing Homes. AB - Purpose of the study: To (a) describe A Scheduled Shifts Staffing measure (ASSiST) to derive care aide worked hours per resident day (HCA WHRD) at facility and unit levels in nursing homes, (b) report reliability through comparisons to administrative staffing data; (c) report validity by examining associations between HCA WHRD, staff outcomes (job satisfaction, emotional exhaustion), and resident quality indicators (QIs) (e.g. falls, delirium, stage 2+ pressure ulcers), and (d) explore intrafacility variation in staffing intensity levels related to unit-level variation in resident and staff outcomes. Design and Methods: We used data from 40 care units in 12 Canadian nursing homes between 2007 and 2012. Descriptive statistics and tests of association and difference described relationships of two measures of staffing with resident and staff outcomes. Results: Annualized rates of HCA WHRD from both data sources compared well at the facility level (Pearson Product Correlation; R = 0.847, p < .001), and were correlated similarly to staff work life and many QIs. Using ASSiST data, we show that staffing levels can vary by up to 40% at the unit-level within nursing homes. Implications: ASSiST is easy to collect, more timely to retrieve than administrative data, has good criterion and construct validity, and reflects intrafacility variation in health care aide staffing levels. PMID- 26884063 TI - Meaningful Activity for Long-Term Care Residents With Dementia: A Comparison of Activities and Raters. AB - Purpose of the Study: Engagement in meaningful activities is associated with positive outcomes for persons with dementia, yet studies demonstrating quantitative evidence for which activities can be considered meaningful are lacking. We investigated MemPicsTM, a program designed to promote meaningful activity for individuals with dementia through engagement and cognitive stimulation. It was compared with other recreation activities offered in U.S. long-term care facilities to determine whether MemPicsTM was rated as having more meaningful activity from both the perspectives of participants and recreation staff. Design and Methods: Long-term care residents with mild to moderate dementia that met eligibility criteria were randomly assigned to an activity group (treatment, control). Participants completed 2 sessions of either the experimental or control group activity with facility recreation staff. Both participants and staff rated each activity in terms of meaningfulness following each session. Results: Of the enrolled participants (N = 126), study analyses were based on the 94 participants (n = 48 treatment and n = 46 control; M age = 82.98+/-9.63) who completed the activity sessions. Compared to the control group activities, MemPicsTM had significantly higher participant and staff ratings of meaningfulness. Scores between the 2 rater types were significantly different, with staff reporting higher meaningful activity than participants. Further support for MemPicsTM was found in exit survey responses from participating staff. Implications: We discuss the merits and shortcoming of this study, the utility of MemPicsTM for providing meaningful engagement in long-term care residents with mild to moderate dementia, and ideas for future research. PMID- 26884065 TI - Aging in Russia. AB - Russia has always been at an intersection of Western and Eastern cultures, with its dozens of ethnic groups and different religions. The federal structure of the country also encompasses a variety of differences in socioeconomic status across its regions. This diversity yields complexity in aging research; aging people in Russia differ in terms of nationality, religion, political beliefs, social and economic status, access to health care, income, living conditions, etc. Thus, it is difficult to control for all these factors or to draw a picture of an "average" Russian older adult. Nevertheless, there is a great deal of research on aging in Russia, mainly focusing on biomedical and social aspects of aging. Most such research is based in the Central and Western regions, whereas the Siberian and Far East regions are underrepresented. There is also a lack of secondary databases and representative nationwide studies. Social policy and legislation address the needs of older adults by providing social services, support, and protection. The retirement system in Russia enables adults to retire at relatively young ages-55 and 60 years for women and men, respectively-but also to maintain the option of continuing their professional career or re-establishing a career after a "vocation" period. Though in recent years the government has faced a range of political issues, affecting the country's economy in general, budget funds for support of aging people have been maintained. PMID- 26884064 TI - Media Portrayal of the Nursing Homes Sector: A Longitudinal Analysis of 51 U.S. Newspapers. AB - Purpose: Most Americans' low opinion of the nursing home (NH) sector could derive, in part, from the way in which it is portrayed in the media. This study furthers understanding of media portrayal of the NH sector by identifying how NHs were depicted in 51U.S. newspapers from 1999 to 2008. Design and methods: Keyword searches of the LexisNexis database were performed to identify 16,280 NH-related articles. Article content was analyzed, and tone, themes, prominence, and central actor were assessed. Basic frequencies and descriptive statistics were used to examine article content across regions, market type, and over time. Results: Findings reveal considerably less NH coverage in the Western United States and a steady decline in NH coverage nationally over time. Most articles were news stories; more than one third were located on the front page of the newspaper or section. Most articles focused on NH industry and government interests, very few on residents/family and community concerns. Most articles were neutral or negative in tone; very few were positive or mixed. Common themes included quality, financing, and legal concerns. Tone, themes, and other article attributes varied across region, market type, and over time. Implications: Overall, findings reveal changes in how newspapers framed NH coverage, not only with respect to tone but also with respect to what dimensions of this complex issue have been emphasized during the time period analyzed. Variation in media coverage may contribute to differences in government and public views toward the NH sector across regions and over time. PMID- 26884066 TI - Well-being of Sibling Caregivers: Effects of Kinship Relationship and Race. AB - Purpose of the Study: This study examined whether caregiving has a differential effect on the well-being of sibling caregivers relative to other caregiving groups and whether race moderates this effect. Design and Methods: Using the National Survey of Midlife Development in the United States, 631 family caregivers (including 61 sibling caregivers) and 4,944 noncaregivers were identified. Hierarchical regression analyses were conducted to estimate the effect of the caregiver-care recipient relationship and its interaction with race on caregivers' well-being (i.e., depressive symptoms, self-rated health, life satisfaction, and perceived control over life). Results: Caregivers in general reported poorer well-being than noncaregivers, but sibling caregivers were less affected by caregiving than parent or spouse caregivers. Among sibling caregivers, caregiving took a significantly greater toll on non-Hispanic White caregivers than those from minority groups with respect to depressive symptoms and life satisfaction. Implication: The findings suggest that the experience of sibling caregivers is significantly shaped by their cultural background. PMID- 26884070 TI - Capillary haemangioma on the palate: a diagnostic conundrum. AB - Haemangiomas are benign tumours of blood vessel origin and are classified as capillary, cavernous or central. They appear as flat or raised reddish-blue lesions and are generally solitary, affecting women in younger age groups. The tumour may be slowly progressive, involving extensive portions of the superficial and deep blood vessels, and affect function, depending on location. They are common in the head and neck region but rarely in the oral cavity. Oral lesions generally appear on the lips, buccal mucosa and tongue, but rarely on the palate. As the lesion can be confused with pyogenic granuloma, histopathological examination is important for a final diagnosis. The case presented here signifies a rare location of a capillary haemangioma on the palate in a middle aged man. The lesion was diagnosed by histopathology after surgical excision. PMID- 26884071 TI - Spontaneous pituitary apoplexy during the second trimester of pregnancy, with sensory loss. AB - A 32-year-old Hispanic woman at 23 weeks gestation presented with right-sided headache, associated with photophobia and right-sided numbness. She denied visual problems, menstrual irregularities and galactorrhoea. Examination revealed visual acuity 20/40 bilaterally with some blurriness on the left side, decreased right V1-V2 facial sensation and preserved 5/5 power, but decreased sensation over the entire right upper extremity (RUE) and right lower extremity (RLE) to touch and pinprick. Laboratories suggested normal pituitary function, but MRI of the brain revealed enlargement of the pituitary (1.7 cm), with layering haemorrhage posteriorly and mild compression of the optic nerve. The patient underwent emergent evacuation of a pituitary haematoma, and histology revealed minute fragments of adenohypophysis with haemorrhage and fibrosis. PMID- 26884069 TI - UHRF1 overexpression is involved in cell proliferation and biochemical recurrence in prostate cancer after radical prostatectomy. AB - BACKGROUND: Biochemical recurrence (BCR) is widely used to define the treatment success and to make decisions on if or how to initiate a secondary therapy, but uniform criteria to define BCR after radical prostatectomy (RP) is not yet completely assessed. UHRF1 has a unique function in regulating the epigenome by linking DNA methylation with histone marks. The clinical value of UHRF1 in PCa has not been well done. Therefore, we evaluated the prognostic significance of UHRF1. METHOD: UHRF1 expression in PCa cells was monitored by qRT-PCR and Western blot analyses. UHRF1 expression was knocked down using specific siRNAs, and the effects of knockdown on the proliferation, migration, cell cycle, and apoptosis of PCa cell lines were investigated. UHRF1 protein expression was evaluated in 225 PCa specimens using immunohistochemistry in tissue microarrays. Correlations between UHRF1 expression and the clinical features of PCa were assessed. RESULTS: The results showed that UHRF1 was overexpressed in almost all of the PCa cell lines. In PCa cells, UHRF1 knockdown inhibited cell proliferation and migration, and induced apoptosis. UHRF1 expression levels were correlated with some clinical features of PCa. Multivariate analysis showed that UHRF1 expression was an independent prognostic factor for biochemical recurrence-free survival. CONCLUSIONS: UHRF1 functions as an oncogene in prostate cancer and appears to be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy, and may serve as a potential therapeutic target for PCa. PMID- 26884072 TI - Rivaroxaban and retropharyngeal haemorrhage. AB - Haemorrhage is a well-known and accepted complication of anticoagulation. A retropharyngeal haemorrhage (RH) is a rare condition that without prompt recognition and management may result in fatal complications. We report a case of RH in a 67-year-old man anticoagulated with rivaroxaban for atrial fibrillation. The patient presented to the emergency department, with a two-day history of atraumatic right-sided neck swelling and associated progressive odynophagia, dysphagia and dysphonia. Rivaroxaban is a potent new oral anticoagulant that has been approved for use by National Institute for Health and Care Excellence (NICE) but still has no approved reversal agent. Despite its rarity, an RH is a potentially life threatening complication of anticoagulation that must be carefully considered. This is especially true for a drug that cannot be easily reversed. We present a discussion of this case presentation with possible differential diagnoses and a review of the literature, and recommend the use of Capp's triad as a diagnostic criterion. PMID- 26884068 TI - The role of APOE in cerebrovascular dysfunction. AB - The epsilon4 allele of the apolipoprotein E gene (APOE4) is associated with cognitive decline during aging, is the greatest genetic risk factor for Alzheimer's disease and has links to other neurodegenerative conditions that affect cognition. Increasing evidence indicates that APOE genotypes differentially modulate the function of the cerebrovasculature (CV), with apoE and its receptors expressed by different cell types at the CV interface (astrocytes, pericytes, smooth muscle cells, brain endothelial cells). However, research on the role of apoE in CV dysfunction has not advanced as quickly as other apoE-modulated pathways. This review will assess what aspects of the CV are modulated by APOE genotypes during aging and under disease states, discuss potential mechanisms, and summarize the therapeutic significance of the topic. We propose that APOE4 induces CV dysfunction through direct signaling at the CV, and indirectly via modulation of peripheral and central pathways. Further, that APOE4 predisposes the CV to damage by, and exacerbates the effects of, additional risk factors (such as sex, hypertension, and diabetes). ApoE4-induced detrimental CV changes include reduced cerebral blood flow (CBF), modified neuron-CBF coupling, increased blood-brain barrier leakiness, cerebral amyloid angiopathy, hemorrhages and disrupted transport of nutrients and toxins. The apoE4-induced detrimental changes may be linked to pericyte migration/activation, astrocyte activation, smooth muscle cell damage, basement membrane degradation and alterations in brain endothelial cells. PMID- 26884067 TI - Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. AB - BACKGROUND: Obesity and type 2 diabetes (T2D) are linked both with host genetics and with environmental factors, including dysbioses of the gut microbiota. However, it is unclear whether these microbial changes precede disease onset. Twin cohorts present a unique genetically-controlled opportunity to study the relationships between lifestyle factors and the microbiome. In particular, we hypothesized that family-independent changes in microbial composition and metabolic function during the sub-clinical state of T2D could be either causal or early biomarkers of progression. METHODS: We collected fecal samples and clinical metadata from 20 monozygotic Korean twins at up to two time points, resulting in 36 stool shotgun metagenomes. While the participants were neither obese nor diabetic, they spanned the entire range of healthy to near-clinical values and thus enabled the study of microbial associations during sub-clinical disease while accounting for genetic background. RESULTS: We found changes both in composition and in function of the sub-clinical gut microbiome, including a decrease in Akkermansia muciniphila suggesting a role prior to the onset of disease, and functional changes reflecting a response to oxidative stress comparable to that previously observed in chronic T2D and inflammatory bowel diseases. Finally, our unique study design allowed us to examine the strain similarity between twins, and we found that twins demonstrate strain-level differences in composition despite species-level similarities. CONCLUSIONS: These changes in the microbiome might be used for the early diagnosis of an inflamed gut and T2D prior to clinical onset of the disease and will help to advance toward microbial interventions. PMID- 26884073 TI - Subarachnoid haemorrhage from the rupture of two intracranial aneurysms in the same day: a rare occurrence, not a myth. AB - The incidence of intracranial aneurysms is approximately 6% throughout the world, although it can be more prevalent in some populations than others. Subarachnoid haemorrhage from a single aneurysm rupture can be devastating, with approximately 35% of patients not regaining consciousness after the initial bleed. In some cases, patients will have two or more aneurysms at presentation, and only one of them will have bled. Having two or more aneurysms that have bled within a few minutes or few hours of one another, is almost unheard of. Our case report is based on a patient who presented with subarachnoid haemorrhage from two ruptured aneurysms, confirmed intraoperatively and corroborated by the available, preoperative, standard head CT scan, which can be performed in any hospital with CT scanning facilities, and CT angiogram. PMID- 26884074 TI - Pregnancy tumour of the external auditory canal: treatment in clinic. AB - We present the case of a 29-year-old woman with a symptomatic lobular capillary haemangioma (pregnancy tumour) arising from the external ear canal. A literature review shows this to be an uncommon lesion in a rare location. The lesion was successfully diagnosed and treated in clinic with complete resolution and no recurrence. PMID- 26884075 TI - Dilated cardiomyopathy with cardiogenic shock in a child with Kearns-Sayre syndrome. AB - Kearns-Sayre syndrome (KSS) is a mitochondrial myopathy resulting from mitochondrial DNA deletion. This syndrome primarily involves the central nervous system, eyes, skeletal muscles and the heart. The most well-known cardiac complications involve the conduction system; however, there have been case reports describing cardiomyopathy. We describe a case of a child with KSS who presented with decompensated cardiac failure from dilated cardiomyopathy representing cardiomyocyte involvement of KSS. Our patient had a rapidly progressing course, despite maximal medical management, requiring emergent institution of extracorporeal membrane oxygenation and transition to a ventricular assist device. To the best of our knowledge, this is the youngest patient in the literature to have dilated cardiomyopathy in KSS. PMID- 26884076 TI - Primary high-grade neuroendocrine carcinoma emerging from an adenomatous polyp in the setting of familial adenomatous polyposis. AB - Familial adenomatous polyposis (FAP) is a rare inherited syndrome that is characterised by innumerable adenomas of the colon and rectum, a high risk of colorectal cancer and a variety of extracolonic manifestations. FAP presents as hundreds to thousands of colonic adenomas beginning in adolescence. The syndrome is associated with less than 1% of all colorectal cancer cases, but there is a nearly 100% lifetime risk of colorectal cancer in individuals with FAP. This case demonstrates a 60-year-old man with FAP who developed high-grade neuroendocrine carcinoma with glandular and squamous differentiation, and regional lymph node and liver metastases. Early diagnosis of FAP is of the utmost importance to start screening colonoscopies to assess disease burden, perform polypectomies and to make management decisions. Neuroendocrine carcinomas rarely occur in patients with FAP, and awareness of this association among general medical physicians and pathologists is essential for the diagnosis and care of these patients. PMID- 26884078 TI - Multimodality imaging and management of an asymptomatic saccular LAD aneurysm. PMID- 26884079 TI - Long-standing meningomyelocele can be a predictor of difficult airway and postoperative hypoventilation: challenge to the anaesthesiologist. AB - A 15-year-old female patient presented with severe pain in the abdomen and obstructive uropathy. She underwent Yang-Monti ileovesicostomy under general anaesthesia. She is a known case of long-standing meningomyelocele (MMC) and presented with its potential complications such as difficult airway and restrictive lung disease. We describe the successful anaesthetic management of a case of anticipated difficult airway and postoperative hypoventilation as a sequel of kyphosis due to MMC. Her airway was secured with fibre optic-guided intubation in a semirecumbent position. Postoperative hypoventilation, hypercarbia and respiratory acidosis were managed conservatively, followed by staged weaning in the intensive care unit. Obstruction of the catheterisable continent channel of the neurogenic bladder itself may present with uropathy and urosepsis, which were also taken care of preoperatively. PMID- 26884077 TI - Hypokalaemia and drinking green tea: a literature review and report of 2 cases. AB - We report the association between excessive consumption of green tea and hypokalaemia in an Oriental couple. Both patients were asymptomatic and the abnormal electrolyte level was only detected on routine blood tests. When they were advised to reduce the consumption of green tea, the abnormally low potassium level was reversed. We have not found such an association reported in the medical literature. The health benefits of green tea consumption are well publicised but the potential side-effects of overconsumption are less well known. We would like to report this association to alert clinicians about this potentially serious complication. This is especially relevant for those who are also taking prescribed medications that can lower potassium levels and/or sensitise patients to potential harm from hypokalaemia. PMID- 26884080 TI - Atypical presentation of a Meckel's diverticulum. PMID- 26884083 TI - Copper-induced ammonia N-H functionalization. AB - The activation of ammonia has been achieved with the aid of the Tp(Ms)Cu core (Tp(Ms) = hydrotris(3-mesityl-pyrazolyl)borate). Complexes of the general composition Tp(Ms)Cu(amine) (1-4) including the ammonia adduct Tp(Ms)Cu(NH3) (1) have been synthesized and fully spectroscopical- and structurally characterized. Coordinated ammonia in 1 has been reacted with Ph3CPF6 yielding Tp(Ms)Cu(NH2CPh3) (5) as a result of N-H cleavage and N-C bond formation. In a parallel manner the catalytic functionalization of ammonia with ethyl diazoacetate leading to glycinate derivatives has been developed with Tp(Ms)Cu(THF) as the catalyst, in the first example of this transformation with ammonia and a copper-based system. PMID- 26884082 TI - Immediate and mid-term result of restrictive mitral annuloplasty using a small semi-rigid ring. AB - OBJECTIVE: Though annuloplasty using a properly sized ring has been advocated in degenerative mitral regurgitation, restrictive annuloplasty using a down-sized ring is widely used in ischemic mitral regurgitation. We investigated the outcome of restrictive annuloplasty using a small (24- or 26-mm) ring in mitral regurgitation irrespective of the etiology. METHODS: Nineteen patients underwent a restrictive annuloplasty using a 24-mm (n = 8) or 26-mm (n = 11) semi-rigid ring. The etiology included degenerative in 13 patients, ischemic in 3, endocarditis in 2, and congenital in 1. Body surface area of the patients implanted with the 24-mm ring was 1.40 +/- 0.16 and 1.60 +/- 0.18 m(2) for the 26 mm ring. Fifteen patients had 3+ or 4+ mitral regurgitation preoperatively. RESULTS: Two patients were converted to valve replacement for residual mitral regurgitation during the operation. One operative mortality associated with infection was observed. Echocardiogram at 29.4 +/- 14.2 months postoperatively demonstrated mitral valve area of 2.0 +/- 0.6 cm(2) for 24-mm ring and 2.2 +/- 0.5 cm(2) for 26-mm ring with indexed mitral valve area of 1.4 +/- 0.4 cm(2)/m(2) for both groups, and no mitral regurgitation more than 2+. Transmitral mean pressure gradient on rest was 4.7 +/- 2.1 mmHg at last follow up. New York Heart Association class improved from 2.2 +/- 0.7 to 1.2 +/- 0.2 after the operation. No late death or reoperation was observed during the follow-up of 31.0 +/- 15.0 months. CONCLUSIONS: Restrictive mitral annuloplasty using a small ring provided acceptable early and midterm results in patients with body surface area around 1.5 cm(2) without Barlow pathology. Restrictive annuloplasty may be another technical aspect to avoid valve replacement. PMID- 26884081 TI - High-sensitivity cardiac troponin T is associated with cognitive decline in older adults at high cardiovascular risk. AB - AIMS: Cardiac troponin T (cTnT), measured with a high-sensitivity (hs) assay, is associated with cognitive decline, but the underlying mechanism is unknown. We investigated the association of hs-cTnT with cognitive function and decline, and studied whether this association was independent of cardiovascular diseases or risk factors, and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: We studied 5407 participants (mean age 75.31 years) from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), who all had cardiovascular diseases or risk factors thereof. Participants with pre-existent advanced clinical heart failure were excluded. Hs-cTnT and NT-proBNP obtained after 6 months of follow-up were related with cognitive function, tested repeatedly during a mean follow-up of 3.2 years. Participants with higher hs-cTnT performed worse at baseline on Stroop test (mean baseline score (standard error (SE)) lowest vs highest third 65.91 (1.16) vs 69.40 (1.10) seconds, p < 0.001), Letter-Digit Coding test (23.35 (0.32) vs 22.40 (0.31) digits coded, p < 0.001), immediate Picture-Word Learning test (9.45 (0.09) vs 9.31 (0.08) pictures remembered, p = 0.002) and delayed Picture-Word Learning test (10.33 (0.12) vs 10.10 (0.12) pictures remembered, p = 0.013). Furthermore, participants with higher hs-cTnT had steeper decline on Stroop test (mean annual change (SE) lowest vs highest third 0.34 (0.12) vs 1.06 (0.12) seconds, p = 0.013), Letter-Digit Coding test (-0.29 (0.03) vs -0.46 (0.03) digits coded, p < 0.001), immediate Picture-Word Learning test (0.01 (0.01) vs -0.06 (0.01) pictures remembered, p < 0.001) and delayed Picture-Word Learning test (-0.03 (0.01) vs -0.12 (0.02) pictures remembered, p = 0.001). Associations were independent of cardiovascular diseases risk factors or Apolipoprotein E genotype. Further adjusting for NT proBNP levels revealed the same results. CONCLUSIONS: Higher levels of hs-cTnT associate with worse cognitive function and steeper cognitive decline in older adults independent of cardiovascular diseases, risk factors and NT-proBNP. PMID- 26884085 TI - 3D nanostructures fabricated by advanced stencil lithography. AB - This letter reports on a novel fabrication method for 3D metal nanostructures using high-throughput nanostencil lithography. Aperture clogging, which occurs on the stencil membranes during physical vapor deposition, is leveraged to create complex topographies on the nanoscale. The precision of the 3D nanofabrication method is studied in terms of geometric parameters and material types. The versatility of the technique is demonstrated by various symmetric and chiral patterns made of Al and Au. PMID- 26884084 TI - Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway. AB - Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERalpha and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERalpha-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer. PMID- 26884086 TI - Co-morbid immunopathological affections in outpatients with inflammatory bowel disease: a prospective study. PMID- 26884087 TI - Memory blindness: Altered memory reports lead to distortion in eyewitness memory. AB - Choice blindness refers to the finding that people can often be misled about their own self-reported choices. However, little research has investigated the more long-term effects of choice blindness. We examined whether people would detect alterations to their own memory reports, and whether such alterations could influence participants' memories. Participants viewed slideshows depicting crimes, and then either reported their memories for episodic details of the event (Exp. 1) or identified a suspect from a lineup (Exp. 2). Then we exposed participants to manipulated versions of their memory reports, and later tested their memories a second time. The results indicated that the majority of participants failed to detect the misinformation, and that exposing witnesses to misleading versions of their own memory reports caused their memories to change to be consistent with those reports. These experiments have implications for eyewitness memory. PMID- 26884088 TI - Taking the easy way out? Increasing implementation effort reduces probability maximizing under cognitive load. AB - Cognitive load has previously been found to have a positive effect on strategy selection in repeated risky choice. Specifically, whereas inferior probability matching often prevails under single-task conditions, optimal probability maximizing sometimes dominates when a concurrent task competes for cognitive resources. We examined the extent to which this seemingly beneficial effect of increased task demands hinges on the effort required to implement each of the choice strategies. Probability maximizing typically involves a simple repeated response to a single option, whereas probability matching requires choice proportions to be tracked carefully throughout a sequential choice task. Here, we flipped this pattern by introducing a manipulation that made the implementation of maximizing more taxing and, at the same time, allowed decision makers to probability match via a simple repeated response to a single option. The results from two experiments showed that increasing the implementation effort of probability maximizing resulted in decreased adoption rates of this strategy. This was the case both when decision makers simultaneously learned about the outcome probabilities and responded to a dual task (Exp. 1) and when these two aspects were procedurally separated in two distinct stages (Exp. 2). We conclude that the effort involved in implementing a choice strategy is a key factor in shaping repeated choice under uncertainty. Moreover, highlighting the importance of implementation effort casts new light on the sometimes surprising and inconsistent effects of cognitive load that have previously been reported in the literature. PMID- 26884089 TI - The Footprint of the Inter-decadal Pacific Oscillation in Indian Ocean Sea Surface Temperatures. AB - Superimposed on a pronounced warming trend, the Indian Ocean (IO) sea surface temperatures (SSTs) also show considerable decadal variations that can cause regional climate oscillations around the IO. However, the mechanisms of the IO decadal variability remain unclear. Here we perform numerical experiments using a state-of-the-art, fully coupled climate model in which the external forcings with or without the observed SSTs in the tropical eastern Pacific Ocean (TEP) are applied for 1871-2012. Both the observed timing and magnitude of the IO decadal variations are well reproduced in those experiments with the TEP SSTs prescribed to observations. Although the external forcings account for most of the warming trend, the decadal variability in IO SSTs is dominated by internal variability that is induced by the TEP SSTs, especially the Inter-decadal Pacific Oscillation (IPO). The IPO weakens (enhances) the warming of the external forcings by about 50% over the IO during IPO's cold (warm) phase, which contributes about 10% to the recent global warming hiatus since 1999. The decadal variability in IO SSTs is modulated by the IPO-induced atmospheric adjustment through changing surface heat fluxes, sea surface height and thermocline depth. PMID- 26884090 TI - CSAHi study: Validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes -assessment of inter-facility and cells lot-to-lot-variability. AB - In vitro screening of hERG channels are recommended under ICH S7B guidelines to predict drug-induced QT prolongation and Torsade de Pointes (TdP), whereas proarrhythmia is known to be evoked by blockage of other ion channels involved in cardiac contraction and compensation mechanisms. A consortium for drug safety assessment using human iPS cells-derived cardiomyocytes (hiPS-CMs), CSAHi, has been organized to establish a novel in vitro test system that would enable better prediction of drug-induced proarrhythmia and QT prolongation. Here we report the inter-facility and cells lot-to-lot variability evaluated with FPDc (corrected field potential duration), FPDc10 (10% FPDc change concentration), beat rate and incidence of arrhythmia-like waveform or arrest on hiPS-CMs in a multi-electrode array system. Arrhythmia-like waveforms were evident for all test compounds, other than chromanol 293B, that evoked FPDc prolongation in this system and are reported to induce TdP in clinical practice. There was no apparent cells lot-to lot variability, while inter-facility variabilities were limited within ranges from 3.9- to 20-folds for FPDc10 and about 10-folds for the minimum concentration inducing arrhythmia-like waveform or arrests. In conclusion, the new assay model reported here would enable accurate prediction of a drug potential for proarrhythmia. PMID- 26884092 TI - Ocular pathological changes in hamsters experimentally infected with Schistosoma mansoni. AB - Ocular lesions have been reported in patients with schistosomiasis; however, the problem with studying schistosomal infection of the human eye is that biopsies are almost impossible to take, and histopathological examination of suspicious lesions can only be undertaken post-mortem or after enucleation. This work aimed to study the possible effects and pathogenesis of schistosomiasis on the eye. This study involved 55 hamsters; five hamsters remained non-infected and the remaining 50 hamsters were infected with Schistosoma mansoni cercariae. Infected hamsters were sacrificed on weeks 8, 12, 16 and 20 post-infection (pi). Eye sections were prepared and stained for histopathological and immunohistochemical studies. Histopathological changes detected in hamsters infected after 16 and 20 weeks included looseness and oedema of the innermost retinal layers together with hyperplastic polypoid growth. Neither eggs nor granulomata were detected in eye sections throughout the experimental period. Deposition of S. mansoni antigen was revealed in 35% of infected hamsters. Later, on weeks 16 and 20 pi, moderate subepithelial conjuctival deposits and marked subchoroidal and scleral deposition were detected. In conclusion, the deposition of schistosomal antigen and immune complexes may play a pivotal role in the ocular changes that occur in schistosomiasis, even in the absence of detectable Schistosoma eggs. Schistosomiasis should be suspected in cases with unexplained ophthalmological findings, especially in endemic areas. PMID- 26884093 TI - Postprandial Hypotension and Coma Following Subarachnoid Hemorrhage in a Patient with Parkinson's Disease. AB - A 79-year-old woman with a history of Parkinson's disease was admitted to our hospital because of a subarachnoid hemorrhage. She underwent clipping the next day. On postoperative days 7-9, she exhibited hypotension and disturbance of consciousness after each meal. The administration of midodrine relieved the hypotension, and postprandial coma was no longer observed. In this case, the autonomic dysfunction in Parkinson's disease and impairment of cerebral autoregulation during cerebral vasospasm may have been involved in the postprandial hypotension (PPH) and coma. PPH occurs not only in patients with Parkinson's disease but also in elderly patients, particularly those with diabetes or hypertension. Therefore, PPH must be considered in the management of cerebral vasospasm following subarachnoid hemorrhage. PMID- 26884091 TI - Subthalamic local field potentials in Parkinson's disease and isolated dystonia: An evaluation of potential biomarkers. AB - Local field potentials (LFP) recorded from the subthalamic nucleus in patients with Parkinson's disease (PD) demonstrate prominent oscillations in the beta (13 30 Hz) frequency range, and reduction of beta band spectral power by levodopa and deep brain stimulation (DBS) is correlated with motor symptom improvement. Several features of beta activity have been theorized to be specific biomarkers of the parkinsonian state, though these have rarely been studied in non parkinsonian conditions. To compare resting state LFP features in PD and isolated dystonia and evaluate disease-specific biomarkers, we recorded subthalamic LFPs from 28 akinetic-rigid PD and 12 isolated dystonia patients during awake DBS implantation. Spectral power and phase-amplitude coupling characteristics were analyzed. In 26/28 PD and 11/12 isolated dystonia patients, the LFP power spectrum had a peak in the beta frequency range, with similar amplitudes between groups. Resting state power did not differ between groups in the theta (5-8 Hz), alpha (8-12 Hz), beta (13-30 Hz), broadband gamma (50-200 Hz), or high frequency oscillation (HFO, 250-350 Hz) bands. Analysis of phase-amplitude coupling between low frequency phase and HFO amplitude revealed significant interactions in 19/28 PD and 6/12 dystonia recordings without significant differences in maximal coupling or preferred phase. Two features of subthalamic LFPs that have been proposed as specific parkinsonian biomarkers, beta power and coupling of beta phase to HFO amplitude, were also present in isolated dystonia, including focal dystonias. This casts doubt on the utility of these metrics as disease-specific diagnostic biomarkers. PMID- 26884094 TI - DHPLC technology for high-throughput detection of mutations in a durum wheat TILLING population. AB - BACKGROUND: Durum wheat (Triticum turgidum L.) is a cereal crop widely grown in the Mediterranean regions; the amber grain is mainly used for the production of pasta, couscous and typical breads. Single nucleotide polymorphism (SNP) detection technologies and high-throughput mutation induction represent a new challenge in wheat breeding to identify allelic variation in large populations. The TILLING strategy makes use of traditional chemical mutagenesis followed by screening for single base mismatches to identify novel mutant loci. Although TILLING has been combined to several sensitive pre-screening methods for SNP analysis, most rely on expensive equipment. Recently, a new low cost and time saving DHPLC protocol has been used in molecular human diagnostic to detect unknown mutations. RESULTS: In this work, we developed a new durum wheat TILLING population (cv. Marco Aurelio) using 0.70-0.85% ethyl methane sulfonate (EMS). To investigate the efficiency of the mutagenic treatments, a pilot screening was carried out on 1,140 mutant lines focusing on two target genes (Lycopene epsilon cyclase, epsilon-LCY, and Lycopene beta-cyclase, beta-LCY) involved in carotenoid metabolism in wheat grains. We simplify the heteroduplex detection by two low cost methods: the enzymatic cleavage (CelI)/agarose gel technique and the denaturing high-performance liquid chromatography (DHPLC). The CelI/agarose gel approach allowed us to identify 31 mutations, whereas the DHPLC procedure detected a total of 46 mutations for both genes. All detected mutations were confirmed by direct sequencing. The estimated overall mutation frequency for the pilot assay by the DHPLC methodology resulted to be of 1/77 kb, representing a high probability to detect interesting mutations in the target genes. CONCLUSION: We demonstrated the applicability and efficiency of a new strategy for the detection of induced variability. We produced and characterized a new durum wheat TILLING population useful for a better understanding of key gene functions. The availability of this tool together with TILLING technique will expand the polymorphisms in candidate genes of agronomically important traits in wheat. PMID- 26884096 TI - Structure determination of the rutile-TiO2(110)-(1 * 2) surface using total reflection high-energy positron diffraction (TRHEPD). AB - The exact structure of the rutile-TiO2(110)-(1 * 2) surface, which had been under debate over the past 30 years, was investigated using the newly developed technique of total-reflection high-energy positron diffraction (TRHEPD), which is a positron counterpart of reflection high-energy electron diffraction (RHEED). The rocking-curves for the 00-spot obtained from the experimental diffraction patterns were compared to the curves for various models calculated with a full dynamical theory. It was found that the rocking-curves matched those for a surface consisting of a Ti2O3 configuration, originally suggested by Onishi and Iwasawa [H. Onishi and Y. Iwasawa, Surf. Sci., 1994, 313, L783], but with a further modification of atomic positions close to the ones proposed by Wang et al. [Q. Wang, A. R. Oganov, Q. Zhu and X. F. Zhou, Phys. Rev. Lett., 2014, 113, 266101]. This result demonstrates that TRHEPD can distinguish between the existence and absence of the oxygen atoms on the topmost surface, and between the Ti atoms residing in positions at the interstitial-vertical sites and those at interstitial-horizontal sites. PMID- 26884095 TI - A two-step patterning process increases the robustness of periodic patterning in the fly eye. AB - Complex periodic patterns can self-organize through dynamic interactions between diffusible activators and inhibitors. In the biological context, self-organized patterning is challenged by spatial heterogeneities ('noise') inherent to biological systems. How spatial variability impacts the periodic patterning mechanism and how it can be buffered to ensure precise patterning is not well understood. We examine the effect of spatial heterogeneity on the periodic patterning of the fruit fly eye, an organ composed of ~800 miniature eye units (ommatidia) whose periodic arrangement along a hexagonal lattice self-organizes during early stages of fly development. The patterning follows a two-step process, with an initial formation of evenly spaced clusters of ~10 cells followed by a subsequent refinement of each cluster into a single selected cell. Using a probabilistic approach, we calculate the rate of patterning errors resulting from spatial heterogeneities in cell size, position and biosynthetic capacity. Notably, error rates were largely independent of the desired cluster size but followed the distributions of signaling speeds. Pre-formation of large clusters therefore greatly increases the reproducibility of the overall periodic arrangement, suggesting that the two-stage patterning process functions to guard the pattern against errors caused by spatial heterogeneities. Our results emphasize the constraints imposed on self-organized patterning mechanisms by the need to buffer stochastic effects. Author summary Complex periodic patterns are common in nature and are observed in physical, chemical and biological systems. Understanding how these patterns are generated in a precise manner is a key challenge. Biological patterns are especially intriguing, as they are generated in a noisy environment; cell position and cell size, for example, are subject to stochastic variations, as are the strengths of the chemical signals mediating cell-to-cell communication. The need to generate a precise and robust pattern in this 'noisy' environment restricts the space of patterning mechanisms that can function in the biological setting. Mathematical modeling is useful in comparing the sensitivity of different mechanisms to such variations, thereby highlighting key aspects of their design.We use mathematical modeling to study the periodic patterning of the fruit fly eye. In this system, a highly ordered lattice of differentiated cells is generated in a two-dimensional cell epithelium. The pattern is first observed by the appearance of evenly spaced clusters of ~10 cells that express specific genes. Each cluster is subsequently refined into a single cell, which initiates the formation and differentiation of a miniature eye unit, the ommatidium. We formulate a mathematical model based on the known molecular properties of the patterning mechanism, and use a probabilistic approach to calculate the errors in cluster formation and refinement resulting from stochastic cell-to-cell variations ('noise') in different quantitative parameters. This enables us to define the parameters most influencing noise sensitivity. Notably, we find that this error is roughly independent of the desired cluster size, suggesting that large clusters are beneficial for ensuring the overall reproducibility of the periodic cluster arrangement. For the stage of cluster refinement, we find that rapid communication between cells is critical for reducing error. Our work provides new insights into the constraints imposed on mechanisms generating periodic patterning in a realistic, noisy environment, and in particular, discusses the different considerations in achieving optimal design of the patterning network. PMID- 26884097 TI - Where Were You? PMID- 26884098 TI - Single Nucleotide Polymorphism (SNP) in the Adiponectin Gene and Cardiovascular Disease. AB - Dear Editor, The recent article by Mohammadzadeh et al.[1] on the latest issue of this Journal showed that the T allele +276G/T SNP of ADIPOQ gene is more associated with the increasing risk of coronary artery disease (CAD) in subjects with type 2 diabetes. Adipocytes were described in myocardial tissue of CAD patients and their role recently discussed[2,3]. Susceptibility to CAD by polymorphism in the Q gene of adiponectin has been reported for 3'-UTR, which harbours some genetic loci associated with metabolic risks and atherosclerosis[4]. Actually, previous studies have shown that the haplotype SNP +276G>T was associated with a decreased risk of CAD, after adjustment for potential confounding factors, therefore some controversial opinion still exists[5]. This evidence should be associated with the role exerted by adipocytes and adiponectin in heart physiology. In particular, in hypertensive disorder complicating pregnancy (HDCP), by investigating the population frequency of alleles, genotypes, and haplotypes of two single nucleotide polymorphisms (SNPs), namely +45T>G (rs2241766) and +276G>T (rs1501299), some authors found that the SNP +276 TT genotype was significantly associated with protection against HDCP, when compared to the pooled G genotypes[6]. Moreover, the same +276G/T SNP haplotype was strongly associated with biliary atresia, an intractable neonatal inflammatory and obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis[7]. CAD is closely related to adiponectin biology. The same isoforms of adiponectin seem to be not associated to CAD severity but to glucose metabolism and its impairment[8]. In the paper by Mohammadzadeh et al.[1], T allele in +276G/T SNP haplotype is highly associated with CAD in subjects with type 2 diabetes, but this linkage should be reappraised if related much more to diabetes rather than CAD. Association of T allele in the indicated SNP with CAD may be an indirect consequence of type 2 diabetes, as reported by others[9] or a direct marker for CAD affected patients[10]. The paper by Mohammadzadeh et al.[1] assesses data coming elsewhere from literature but raises important concerns about the suitability of ADIPOQ SNPs in diagnosing susceptibility to CAD and the relationship with plasma adiponectin level. In normal, non diabetic, normoglycemic subject, this relationship does not seem to work. Therefore the question is how much predictive this SNP haplotype may be to foresee metabolic syndrome and CAD onset risk in young health subjects? Maybe, the role of adiponectin in cardiovascular physiology depends on its ability to target adiponectin receptors and to negatively regulate obesity. Some authors reported in healthy volunteers an absence of correlation between circulating adiponectin levels and biochemical markers, particularly lipoproteins and suggested that SNP +276G>T was related to an independent effect on adiponectin levels and on lipoprotein metabolism[11]. On the contrary, adiponectin genetic variants and SNP +276G>T was associated with increasing susceptibility of type 2 diabetes and plasma glucose impairment[12]. The interesting study by Mohammadzadeh et al.[1] suggests that SNP of ADIPOQ +276G>T should be related to susceptibility to glucose metabolism, while indirectly to lipid metabolism and fat-related cardiovascular damage. PMID- 26884099 TI - Paraoxonase-1 (PON1) inhibition by tienilic acid produces hepatic injury: Antioxidant protection by fennel extract and whey protein concentrate. AB - This study evaluated the effect of whey protein concentrate (WPC) or fennel seed extract (FSE) on paraoxonase-1 activity (PON1) and oxidative stress in liver of tienilic acid (TA) treated rats. Six groups of rats were treated for six weeks as follows: control; WPC (0.5g/kg/day); FSE (200mg/ kg/day); TA (1g/kg/twice a week); TA (1g/kg/twice a week) plus WPC (0.5g/kg/day); TA (1g/kg/twice a week) plus FSE (200mg/kg/day). TA administration significantly increased ALT and AST besides to total- and direct bilirubin levels. Also, serum tumor necrosis factor alpha and nitric oxide levels were significantly increased. Furthermore, serum PON1, and hepatic reduced glutathione, glutathione-S-transferase and Na(+)/K(+) ATPase values were diminished matched with a significant rise in the level of hepatic lipid peroxidation. Also, triglycerides, total- and LDL-cholesterol levels were significantly elevated while HDL-cholesterol was unchanged. The administration of either WPC or FSE to TA-treated animals significantly protected the liver against the injurious effects of tienilic acid. This appeared from the improvement of hepatic functions, atherogenic markers, Na(+)/K(+) ATPase activity, endogenous antioxidants and hepatic lipid peroxidation level; where WPC showed the strongest protection effect. In conclusion, the present study indicated that WPC and FSE improve PON1 activity and attenuate liver dysfunction induced by TA. This may be attributed to the high content of antioxidant compounds in WPC and fennel extract. PMID- 26884100 TI - Polyarteritis nodosa: A contemporary overview. AB - Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis predominantly targeting medium-sized arteries. PAN is a rare form of vasculitis, and the precise frequency of this disease is difficult to determine. The major environmental factor associated with PAN is HBV infection. The pathogenesis of "idiopathic PAN" remains enigmatic, although the clinical responses to immunosuppressive therapy support the concept that immunological mechanisms play an active pathogenic role. The spectrum of disease ranges from involving a single organ to polyvisceral failure. Any organ might be affected; however, for reasons that are not understood, PAN does not affect the lungs. In addition to the systemic idiopathic form, called "idiopathic generalized PAN," there are 2 clinical variants of this disease: "cutaneous PAN" and "hepatitis B virus (HBV) associated PAN". Diagnosis requires the integration of clinical, angiographic, and biopsy findings. The overall prognosis of this disease has been improved in recent decades, primarily reflecting early diagnosis and more effective treatments. Idiopathic generalized PAN should be treated with a combination of glucocorticoids and cyclophosphamide. The treatment of HBV-associated PAN involves a different approach, centered on the use of an antiviral agent to control the infection. The therapy for cutaneous PAN requires a less aggressive approach based on the administration of non-steroidal anti-inflammatory drugs over short periods of time. PMID- 26884101 TI - Chromosome Aberrations and Fertility Disorders in Domestic Animals. AB - The association between chromosomal abnormalities and reduced fertility in domestic animals is well recorded and has been studied for decades. Chromosome aberrations directly affect meiosis, gametogenesis, and the viability of zygotes and embryos. In some instances, balanced structural rearrangements can be transmitted, causing fertility problems in subsequent generations. Here, we aim to give a comprehensive overview of the current status and future prospects of clinical cytogenetics of animal reproduction by focusing on the advances in molecular cytogenetics during the genomics era. We describe how advancing knowledge about animal genomes has improved our understanding of connections between gross structural or molecular chromosome variations and reproductive disorders. Further, we expand on a key area of reproduction genetics: cytogenetics of animal gametes and embryos. Finally, we describe how traditional cytogenetics is interfacing with advanced genomics approaches, such as array technologies and next-generation sequencing, and speculate about the future prospects. PMID- 26884102 TI - Perspectives from the Avian Phylogenomics Project: Questions that Can Be Answered with Sequencing All Genomes of a Vertebrate Class. AB - The rapid pace of advances in genome technology, with concomitant reductions in cost, makes it feasible that one day in our lifetime we will have available extant genomes of entire classes of species, including vertebrates. I recently helped cocoordinate the large-scale Avian Phylogenomics Project, which collected and sequenced genomes of 48 bird species representing most currently classified orders to address a range of questions in phylogenomics and comparative genomics. The consortium was able to answer questions not previously possible with just a few genomes. This success spurred on the creation of a project to sequence the genomes of at least one individual of all extant ~10,500 bird species. The initiation of this project has led us to consider what questions now impossible to answer could be answered with all genomes, and could drive new questions now unimaginable. These include the generation of a highly resolved family tree of extant species, genome-wide association studies across species to identify genetic substrates of many complex traits, redefinition of species and the species concept, reconstruction of the genomes of common ancestors, and generation of new computational tools to address these questions. Here I present visions for the future by posing and answering questions regarding what scientists could potentially do with available genomes of an entire vertebrate class. PMID- 26884103 TI - Bovine Tuberculosis in Cattle: Vaccines, DIVA Tests, and Host Biomarker Discovery. AB - Bovine tuberculosis remains a major economic and animal welfare concern worldwide. Cattle vaccination is being considered as part of control strategies. This approach, used alongside conventional control policies, also requires the development of vaccine-compatible diagnostic assays to distinguish vaccinated from infected animals (DIVA). We discuss progress made on optimizing the only potentially available vaccine, bacille Calmette Guerin (BCG), and on strategies to improve BCG efficacy. We also describe recent advances in DIVA development based on the detection of host cellular immune responses by blood-testing or skin testing approaches. Finally, to accelerate vaccine development, definition of host biomarkers that provide meaningful stage-gating criteria to select vaccine candidates for further testing is highly desirable. Some progress has also been made in this area of research, and we summarize studies that defined either markers predicting vaccine success or markers that correlate with disease stage or severity. PMID- 26884104 TI - Innovations in Canine and Feline Nutrition: Technologies for Food and Nutrition Assessment. AB - Pet owners have increasing concerns about the nutrition of their pets, and they desire foods and treats that are safe, traceable, and of high nutritive value. To meet these high expectations, detailed chemical composition characterization of ingredients well beyond that provided by proximate analysis will be required, as will information about host physiology and metabolism. Use of faster and more precise analytical methodology and novel technologies that have the potential to improve pet food safety and quality will be implemented. In vitro and in vivo assays will continue to be used as screening tools to evaluate nutrient quality and adequacy in novel ingredients prior to their use in animal diets. The use of molecular and high-throughput technologies allows implementation of noninvasive studies in dogs and cats to investigate the impact of dietary interventions by using systems biology approaches. These approaches may further improve the health and longevity of pets. PMID- 26884105 TI - Introduction. PMID- 26884106 TI - "Prince Charles Is Living With Me": When This Is (Not) a Delusion. PMID- 26884107 TI - Utility of Montreal Cognitive Assessment (Hong Kong Version) in the Diagnosis of Mild Neurocognitive Disorders (NCD): NCD due to Alzheimer Disease (NCD-AD) and NCD due to Vascular Disease (NCD-Vascular). PMID- 26884108 TI - "Post-Acute Care 2.0" Regarding Burke RE, Whitfield EA, Hittle D, et al. Hospital Readmission From Post-Acute Care Facilities: Risk Factors, Timing, and Outcomes. PMID- 26884109 TI - Ongoing risk stratification for differentiated thyroid cancer (DTC) - stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients. AB - INTRODUCTION: Adequate postoperative risk assessment currently constitutes the principle of DTC treatment and further management. The aim of the study - a retrospective assessment of risk factors influencing DTC relapse. MATERIAL AND METHODS: The study group consisted of 510 DTC staged pT1b-T4N0-N1M0, in whom total thyroidectomy and complementary radioiodine (RAI) treatment were carried out. In 71% papillary thyroid cancer was diagnosed, whereas in the remaining 29% follicular thyroid carcinoma. Based on TNM classification from 1997, T1 feature was diagnosed in 11.6%, T2 in 35.1%, T3 in 8.4%, T4 in 9,4%, while in 35.5% - Tx. Lymph node metastases were present in 24.7% of cases. Median follow-up was 12.1 years (1.5-15.2). RESULTS: Age at DTC diagnosis, tumour diameter (T), lymph node metastases (N1), stimulated thyroglobulin, and RAI uptake in thyroid bed at qualification for RAI ablation significantly influenced freedom from progression time (FFP) in a multivariate analysis. When postoperative stimulated Tg was > 30 ng/mL the risk of relapse increased nearly six-fold, whereas the presence of N1 feature - four-fold. The total risk of relapse in the whole group was 12.55% while median FFP was 154.8 months. Five-year and 10-year FFP was 90.1% and 87.5%, respectively. CONCLUSIONS: Postoperative stimulated thyroglobulin level was the most potent, independent risk factor influencing FFP in DTC patients. Age above 60 years, an initial DTC stage (T and N features), and low RAI uptake in thyroid bed ( < 1%) were related to a higher risk of DTC relapse, whereas the investigated histopathological features were insignificant. PMID- 26884110 TI - Clinical importance of follicular lesion of undetermined significance (diagnostic category III according to Bethesda System) diagnosed from Fine-Needle Aspiration Biopsy. AB - INTRODUCTION: Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). MATERIAL AND METHODS: Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. RESULTS: From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of "Papillary Thyroid Carcinoma" and one "Suspicious for Papillary Thyroid Carcinoma". From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was "Suspicious for Malignancy". In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. CONCLUSIONS: The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment. PMID- 26884111 TI - Suspicious for follicular neoplasm or follicular neoplasm? The dilemma of a pathologist and a surgeon. AB - INTRODUCTION: Cytological material obtained from Fine Needle Aspiration Biopsy (FNAB) does not permit us to distinguish between follicular carcinomas, adenomas, and hyperplastic nodules. The limitations of the method are: lack of possibility to assess the presence of tumour capsule, eventual capsular invasion, and angioinvasion. An unequivocal conclusion of whether what we have to deal with is a neoplastic or benign lesion is possible only after histopathological examination. The aim of the study was to confirm justification for using the term "Suspicious for Follicular Neoplasm" (SFN) in cytological diagnostics of thyroid carcinoma. MATERIAL AND METHODS: Three hundred and fifty-two primary SFN FNAB diagnoses (diagnostic category IV [DC IV] - according to Bethesda System) obtained from 2010 to 2015 in the Institute of Oncology in Gliwice were analysed, and their correlation with histopathological diagnoses was verified. RESULTS: In the Institute of Oncology in Gliwice, 352 primary SFN diagnoses (diagnostic category IV [DC IV] - according to Bethesda System) were established. Surgical treatment was undertaken after first FNAB in six cases, giving confirmation of a neoplasm in five cases, one of which was a follicular carcinoma. Second FNAB performed in 90 patients confirmed DC IV diagnosis in 53 cases. Third FNAB concerned 26 patients, providing another 14 diagnoses of DC IV. 26 out of 352 patients were subjected to surgery, and then histopathological examination confirmed a neoplasm in 19 cases (which comprises 73%), five of which were carcinomas. CONCLUSIONS: High positive predictive value PPV = 73% of SFN diagnosis justifies undertaking surgical treatment in any case of this diagnosis. PMID- 26884112 TI - Analysis of clinical significance of equivocal thyroid cytology with a special consideration for FLUS category - five years of new classification of FNA results. AB - INTRODUCTION: The diagnostic category of follicular lesion of undetermined significance (FLUS) was intended to allow selection of cases with low risk of malignancy from all smears with indeterminate, suspicious cytology (ISC), which can potentially take advantage from repeat fine-needle aspiration (rFNA). Aim of the study was a comparison of the risk of malignancy related to FLUS nodules and other nodules with ISC: suspected follicular neoplasm (SFN) and suspected malignancy (SM), as well as analysis of the usefulness of assessing ultrasonographic malignancy risk features (UMRF) in nodules with ISC. MATERIAL AND METHODS: We analysed UMRF, rFNA, and results of histopathological examination (H) in 441 FLUS, 135 SFN, and 72 SM nodules. RESULTS: The frequency of exposing cancer in H in FLUS nodules was 5.9%, and when cytological follow up was also included it was 2.9%. rFNAs made the diagnosis more precise in 72.7% of FLUS, and in 5.2% it was diagnosis/suspicion of cancer. The incidence of cancer in SFN nodules was 8.2%, in SM nodules with suspicion of papillary cancer - 61.1%, and in nodules with suspicion of other or unspecified malignancy - 53.8% (p < 0.0001 FLUS vs. both groups). The presence of calcifications is the only independent UMRF for nodules with ISC (OR 4.7). Features of importance are also microcalcifications (OR 3.8), especially in the SM group, and taller-than-wide shape (OR 2.2). FLUS and SFN nodules are characterised by particularly low value of assessing suspicious margins; analysis of hypoechogenicity is of low value in SFN nodules, like suspected vascularisation in SFN and SM nodules. CONCLUSIONS: The risk of cancer in FLUS and SFN nodules is lower than in SM nodules. rFNAs of FLUS nodules make the diagnosis more precise in more than 70% of cases and are effective in revealing cancers. UMRFs present variable diagnostic value depending on the subcategory of ISC. PMID- 26884113 TI - The value of the repeated examination of BRAF V600E mutation status in diagnostics of papillary thyroid cancer. AB - INTRODUCTION: Nodular thyroid disease is one of the most frequently diagnosed pathologies of the adult population in iodine-deficient regions. Approximately 30% of thyroid aspirates are classified as nondiagnostic/unsatisfactory or indeterminate. However, patients with indeterminate cytology still undergo surgery. The object of this study was to determine the diagnostic value of re examining the BRAF V600E mutation in papillary thyroid carcinoma patients. MATERIAL AND METHODS: All patients underwent ultrasound guided fine-needle aspiration of a thyroid nodule. They were assigned to one of the four groups (indeterminate or positive for malignant cells) of the Bethesda System for Reporting Thyroid Cytopathology. Genetic investigation of the BRAF V600E mutation was performed for all of the fine-needle aspiration cytology specimens. All of the patients underwent surgery. Subsequently, histological investigation of the removed tissues was performed. Additional analysis of the BRAF V600E mutation from the histology specimen was then performed for the initially BRAF-negative cases. RESULTS: Two hundred and fourteen patients were involved in the study. One hundred and six (49.53%) patients were diagnosed with thyroid cancer. Of these 106 patients, 95 (89.62%) patients were diagnosed with papillary thyroid cancer. The BRAF V600E mutation was positive in 62 (65.26%) and negative in 33 (34.74%) histologically confirmed papillary thyroid cancer cases. After the genetic investigation, a total of 74 (77.89%) papillary thyroid cancer cases were positive for the BRAF V600E mutation and 21 (22.11%) were negative. CONCLUSIONS: Repeated examination of the BRAF V600E mutation status in the fine-needle aspiration may potentially increase the sensitivity of papillary thyroid cancer diagnostics. PMID- 26884114 TI - The usefulness of determining the presence of BRAF V600E mutation in fine-needle aspiration cytology in indeterminate cytological results. AB - INTRODUCTION: Fine-needle aspiration biopsy (FNAB) is regarded as the gold standard method for the diagnosis of thyroid nodules, but it has its limitations. Additional methods that would improve sensitivity and specificity in the diagnosis of thyroid cancer (TC), especially in indeterminate lesions. Molecular tests seem to be such a tool. BRAF V600E mutation (the most common in TC) can be detected in FNAB and can be potentially a very useful ancillary marker for FNAB practice. The aim of our study was to evaluate the usefulness of the detection of the BRAF V600E mutation in FNAC in the early diagnosis of TC in patients with indeterminate cytology. MATERIAL AND METHOD: 2290 FNAB were performed and 147 indeterminate results (group 3, 4, and 5 of the Bethesda system) were obtained. Material from these groups was submitted for molecular tests for the occurrence of BRAF V600E mutation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the tests were calculated. RESULTS: Determining the presence of BRAF V600E mutation in FNAC material in groups 3 and 4 together and in group 5 is associated with sensitivity of TC diagnosis of 37.5% and 81.8%, respectively. In all cases the detection of BRAF V600E mutation was associated with histopathologically proving the presence of TC (specificity of the test - 100%). CONCLUSIONS: The presence of BRAF V600E mutation in FNAC material is always associated with the presence of TC. The usefulness of determining the presence of BRAF V600E in FNAC in cytological groups 3 and 4 is associated with low sensitivity in the diagnosis of thyroid cancer. Due to its high specificity BRAF V600E study may be useful in determining the scope of surgery in patients in cytological group 5. PMID- 26884115 TI - Impact of Hashimoto's thyroiditis, TSH levels, and anti-thyroid antibody positivity on differentiated thyroid carcinoma incidence. AB - INTRODUCTION: The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear. MATERIAL AND METHODS: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC. RESULTS: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate. CONCLUSIONS: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT. PMID- 26884116 TI - Occurrence of phaeochromocytoma tumours in RET mutation carriers - a single centre study. AB - INTRODUCTION: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant genetic syndrome caused by germline mutation in RET proto-oncogene. The most common mutations are in a cysteine rich domain. Phaeochromocytoma will develop in approximately 50% of RET proto-oncogene carriers. MATERIAL AND METHODS: The studied population consisted of 228 RET proto-oncogene mutation carriers. Monitoring for the diagnosis of phaeochromocytoma was carried out in all patients with established genetic status. Mean time of follow up was 138 months. Surveillance consisted of periodically performed clinical evaluation, 24 hour urinary determinations of total metanephrines complementary with imaging (CT, MR, MIBG scintigraphy). RESULTS: Phaeochromocytoma developed in 41 patients (18% of all RET proto-oncogene mutations carriers). The mean age of diagnosis for the whole cohort was 43 years. In eight cases phaeochromocytoma was the first manifestation of the MEN 2 syndrome. Only eight (20%) patients were symptomatic at diagnosis of phaeochromocytoma. The mean size of the tumour was 4.3 cm. There was no extra-adrenal localisation. We observed one case of malignant phaeochromocytoma. CONCLUSIONS: In patients with MEN 2 syndrome phaeochromocytomas are usually benign adrenal tumours with high risk of bilateral development. Taking to account the latter risk and non-specific clinical manifestation of the neoplasm it is mandatory to screen all RET proto-oncogene mutations carriers for phaeochromocytoma. PMID- 26884117 TI - Well-differentiated thyroid cancer - are you overtreating your patients? AB - Over the last 50 years there has been a move towards more aggressive therapy for well-differentiated thyroid cancer. In recent times, however, international guidelines have shown some trend back towards a more conservative approach to treating low-risk patients. This review explores how the state of the art in well differentiated thyroid cancer research has evolved in tandem with improvements in risk-stratification. A focus on the surgical approach to the primary thyroid tumour and the regional lymphatics in addition to the interplay between surgical decision making and the use of radioactive iodine are presented to allow the reader to determine whether they are now overtreating patients with well differentiated thyroid cancer. PMID- 26884118 TI - Medullary thyroid carcinoma - PET/CT imaging with 68Ga-labelled gastrin and somatostatin analogues. AB - CASE PRESENTATION: a 75-year-old man with a 10-year history of nodular goitre was referred for clinical evaluation. The ultrasound scan revealed enlarged thyroid right lobe almost fully filled with a heterogeneous nodule with numerous calcifications. Fine-needle aspiration biopsy suggested medullary thyroid carcinoma (MTC). Before the surgery the patient was referred to the nuclear medicine department and somatostatin receptor imaging (SRS; 68Ga-DOTATATE) with PET/CT was performed. The scan demonstrated an increased uptake within the right thyroid mass. Subsequent PET/CT with 68Ga-gastrin analogue (MG48) revealed the same indications as the SRS: an increased alveolar uptake in the right thyroid mass without the signs of lymph node metastases. The patient underwent total thyroidectomy and central lymph nodes dissection. Histopathology examination confirmed the presence of MTC with vascular invasion, but without lymph node metastases (pT3NoMx according to the 7th edition of the AJCC Cancer Staging Manual). Immunohistochemical staining revealed positive reaction to calcitonin and CD56, whereas the reaction to thyroglobulin remained negative. The Ki-67 was 1%. Staining for SSTR2 and CCK2 showed high cytoplasmic expression in both cases. Knowledge of the presence of CCK2 receptor in MTC patients may be an important indication for the choice of diagnostic and therapeutic procedures. The presence of both the receptor types, cholecystokinin-2/gastrin and somatostatin, is possibly an interesting combination as far as the therapeutic target is concerned. PMID- 26884119 TI - Diagnostics and Treatment of Thyroid Carcinoma. AB - Revised Guidelines of Polish National Societies Prepared on the initiative of the Polish Group for Endocrine Tumours approved in their final version between November 16th and 28th, 2015 by the Scientific Committee of the V Conference "Thyroid Cancer and other malignancies of endocrine glands" organised between November 14th and 17th, 2015 in Wisla, Poland; called by the following Societies: Polish Endocrine Society, Polish Society of Oncology, Polish Thyroid Association, Polish Society of Pathologists, Society of Polish Surgeons, Polish Society of Surgical Oncology, Polish Society of Clinical Oncology, Polish Society of Radiation Oncology, Polish Society of Nuclear Medicine, Polish Society of Paediatric Endocrinology, Polish Society of Paediatric Surgeons, Polish Society of Ultrasonography Gliwice-Wisla, 2015 DECLARATION: These recommendations are created by the group of delegates of the National Societies, which declare their willingness to participate in the preparation of the revised version of the Polish Guidelines. The members of the Working Group have been chosen from the specialists involved in medical care of patients with thyroid carcinoma. Directly before the preparation of the Polish national recommendations the American Thyroid Association (ATA) published its own guidelines together with a wide comment fulfilling evidence-based medicine (EBM) criteria. ATA Guidelines are consistent with National Comprehensive Cancer Network (NCCN) Recommendation. According to the members of the Working Group, it is necessary to adapt them to both the specific Polish epidemiological situation as well as to the rules referring to the Polish health system. Therefore, the Polish recommendations constitute a consensus of the experts' group, based on ATA information. The experts analysed previous Polish Guidelines, published in 2010, and other available data, and after discussion summed up the results in the form of these guidelines. It should be added that Part II, which constitutes a pathological part, has been available at the website of the Polish Society of Pathologists for acceptance of the members of the Society, and no essential comments have been proposed. The Members of the Group decided that a subgroup elected from among them would update the Guidelines, according to EBM rules, every year. The Revised Guidelines should help physicians to make reasonable choices in their daily practice; however, the final decision concerning an individual patient should be made by the caring physician responsible for treatment, or optimally by a therapeutic tumour board together with the patient, and should take into consideration the patient's health condition. It should be emphasised that the recommendations may not constitute a strict standard of clinical management imposed on medical staff. The data from clinical trials concerning numerous clinical situations are scarce. In such moments the opinion of the management may differ from the recommendations after considering possible benefits and disadvantages for the patient. PMID- 26884120 TI - World Kidney Day 2016: Averting the legacy of kidney disease-focus on childhood. AB - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early, or who are small-for-date newborns, have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy-makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID- 26884121 TI - Assessment of anxiety in open field and elevated plus maze using infrared thermography. AB - Due to their direct inaccessibility, affective states are classically assessed by gathering concomitant physiological and behavioral measures. Although such a dual approach to assess emotional states is frequently used in different species including humans, the invasiveness of procedures for physiological recordings particularly in smaller-sized animals strongly restricts their application. We used infrared thermography, a non-invasive method, to assess physiological arousal during open field and elevated plus maze tests in mice. By measuring changes in surface temperature indicative of the animals' emotional response, we aimed to improve the inherently limited and still controversial information provided by behavioral parameters commonly used in these tests. Our results showed significant and consistent thermal responses during both tests, in accordance with classical physiological responses occurring in stressful situations. Besides, we found correlations between these thermal responses and the occurrence of anxiety-related behaviors. Furthermore, initial temperatures measured at the start of each procedure (open field, elevated plus maze), which can be interpreted as a measure of the animals' initial physiological arousal, predicted the levels of activity and of anxiety-related behaviors displayed during the tests. Our results stress the strong link between physiological correlates of emotions and behaviors expressed during unconditioned fear tests. PMID- 26884122 TI - A dual-process approach to exploring the role of delay discounting in obesity. AB - Delay discounting of financial rewards has been related to overeating and obesity. Neuropsychological evidence supports a dual-system account of both discounting and overeating behaviour where the degree of impulsive decision making is determined by the relative strength of reward desire and executive control. A dual-parameter model of discounting behaviour is consistent with this theory. In this study, the fit of the commonly used one-parameter model was compared to a new dual-parameter model for the first time in a sample of adults with wide ranging BMI. Delay discounting data from 79 males and females (males=26) across a wide age (M=28.44years (SD=8.81)) and BMI range (M=25.42 (SD=5.16)) was analysed. A dual-parameter model (saturating-hyperbolic; Doya, [Doya (2008) ]) was applied to the data and compared on model fit indices to the single-parameter model. Discounting was significantly greater in the overweight/obese participants using both models, however, the two parameter model showed a superior fit to data (p<0.0001). The two parameters were shown to be related yet distinct measures consistent with a dual-system account of inter temporal choice behaviour. The dual-parameter model showed superior fit to data and the two parameters were shown to be related yet distinct indices sensitive to differences between weight groups. Findings are discussed in terms of the impulsive reward and executive control systems that contribute to unhealthy food choice and within the context of obesity related research. PMID- 26884123 TI - A theoretical prediction of super high-performance thermoelectric materials based on MoS2/WS2 hybrid nanoribbons. AB - Modern society is hungry for electrical power. To improve the efficiency of energy harvesting from heat, extensive efforts seek high-performance thermoelectric materials that possess large differences between electronic and thermal conductance. Here we report a super high-performance material of consisting of MoS2/WS2 hybrid nanoribbons discovered from a theoretical investigation using nonequilibrium Green's function methods combined with first principles calculations and molecular dynamics simulations. The hybrid nanoribbons show higher efficiency of energy conversion than the MoS2 and WS2 nanoribbons due to the fact that the MoS2/WS2 interface reduces lattice thermal conductivity more than the electron transport. By tuning the number of the MoS2/WS2 interfaces, a figure of merit ZT as high as 5.5 is achieved at a temperature of 600 K. Our results imply that the MoS2/WS2 hybrid nanoribbons have promising applications in thermal energy harvesting. PMID- 26884124 TI - Treating hypertension in patients with medical comorbidities. PMID- 26884125 TI - Non-variceal upper gastrointestinal bleeding in cirrhotic patients in Nile Delta. AB - BACKGROUND AND STUDY AIMS: Acute upper gastrointestinal bleeding (AUGIB) in cirrhotic patients occurs mainly from esophageal and gastric varices; however, quite a large number of cirrhotic patients bleed from other sources as well. The aim of the present work is to determine the prevalence of non-variceal UGIB as well as its different causes among the cirrhotic portal hypertensive patients in Nile Delta. METHODS: Emergency upper gastrointestinal (UGI) endoscopy for AUGIB was done in 650 patients. Out of these patients, 550 (84.6%) patients who were proved to have cirrhosis were the subject of the present study. RESULTS: From all cirrhotic portal hypertensive patients, 415 (75.5%) bled from variceal sources (esophageal and gastric) while 135 (24.5%) of them bled from non-variceal sources. Among variceal sources of bleeding, esophageal varices were much more common than gastric varices. Peptic ulcer was the most common non-variceal source of bleeding. CONCLUSIONS: Non-variceal bleeding in cirrhosis was not frequent, and sources included peptic ulcer, portal hypertensive gastropathy, and erosive disease of the stomach and duodenum. PMID- 26884126 TI - Two Defibrillators and Two Cases are Better than One. PMID- 26884127 TI - Pelvic Free Fluid in Asymptomatic Pediatric Blunt Abdominal Trauma Patients: A Case Series and Review of the Literature. AB - BACKGROUND: With focused assessment with sonography in trauma (FAST) examinations being performed more commonly on pediatric trauma patients, emergency providers will encounter a positive FAST examination in patients with benign abdominal examinations. This poses a diagnostic dilemma for the provider when deciding whether to obtain a computed tomography (CT) scan of the abdomen/pelvis, observe the patient, or admit the patient. CASE REPORT: We report a series of pediatric patients involved in blunt abdominal trauma who had small pelvic free fluid on FAST but a benign abdominal examination. Three patients were managed without CT scan and 2 with CT scan. All patients did well and were discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Free intra-abdominal fluid may be physiologic in both male and female pediatric patients. Clinical examination and hemodynamic stability should be taken into account when deciding to order a CT scan. We review the literature and highlight new protocols that may decrease CT utilization and ionizing radiation exposure, though further studies in this specific population are needed. PMID- 26884129 TI - Contribution of Dielectric Screening to the Total Capacitance of Few-Layer Graphene Electrodes. AB - We apply joint density functional theory (JDFT), which treats the electrode/electrolyte interface self-consistently, to an electric double-layer capacitor (EDLC) based on few-layer graphene electrodes. The JDFT approach allows us to quantify a third contribution to the total capacitance beyond quantum capacitance (CQ) and EDL capacitance (CEDL). This contribution arises from the dielectric screening of the electric field by the surface of the few-layer graphene electrode, and we therefore term it the dielectric capacitance (CDielec). We find that CDielec becomes significant in affecting the total capacitance when the number of graphene layers in the electrode is more than three. Our investigation sheds new light on the significance of the electrode dielectric screening on the capacitance of few-layer graphene electrodes. PMID- 26884128 TI - Rapid multiplex detection of 10 foodborne pathogens with an up-converting phosphor technology-based 10-channel lateral flow assay. AB - The rapid high-throughput detection of foodborne pathogens is essential in controlling food safety. In this study, a 10-channel up-converting phosphor technology-based lateral flow (TC-UPT-LF) assay was established for the rapid and simultaneous detection of 10 epidemic foodborne pathogens. Ten different single target UPT-LF strips were developed and integrated into one TC-UPT-LF disc with optimization. Without enrichment the TC-UPT-LF assay had a detection sensitivity of 10(4) CFU mL(-1) or 10(5) CFU mL(-1) for each pathogen, and after sample enrichment it was 10 CFU/0.6 mg. The assay also showed good linearity, allowing quantitative detection, with a linear fitting coefficient of determination (R(2)) of 0.916-0.998. The 10 detection channels did not cross-react, so multiple targets could be specifically detected. When 279 real food samples were tested, the assay was highly consistent (100%) with culture-based methods. The results for 110 food samples artificially contaminated with single or multiple targets showed a high detection rate (>= 80%) for most target bacteria. Overall, the TC UPT-LF assay allows the rapid, quantitative, and simultaneous detection of 10 kinds of foodborne pathogens within 20 min, and is especially suitable for the rapid detection and surveillance of foodborne pathogens in food and water. PMID- 26884130 TI - When audiovisual correspondence disturbs visual processing. AB - Multisensory integration is known to create a more robust and reliable perceptual representation of one's environment. Specifically, a congruent auditory input can make a visual stimulus more salient, consequently enhancing the visibility and detection of the visual target. However, it remains largely unknown whether a congruent auditory input can also impair visual processing. In the current study, we demonstrate that temporally congruent auditory input disrupts visual processing, consequently slowing down visual target detection. More importantly, this cross-modal inhibition occurs only when the contrast of visual targets is high. When the contrast of visual targets is low, enhancement of visual target detection is observed, consistent with the prediction based on the principle of inverse effectiveness (PIE) in cross-modal integration. The switch of the behavioral effect of audiovisual interaction from benefit to cost further extends the PIE to encompass the suppressive cross-modal interaction. PMID- 26884131 TI - Viewing the body modulates both pain sensations and pain responses. AB - Viewing the body can influence pain perception, even when vision is non informative about the noxious stimulus. Prior studies used either continuous pain rating scales or pain detection thresholds, which cannot distinguish whether viewing the body changes the discriminability of noxious heat intensities or merely shifts reported pain levels. In Experiment 1, participants discriminated two intensities of heat-pain stimulation. Noxious stimuli were delivered to the hand in darkness immediately after participants viewed either their own hand or a non-body object appearing in the same location. The visual condition varied randomly between trials. Discriminability of the noxious heat intensities (d') was lower after viewing the hand than after viewing the object, indicating that viewing the hand reduced the information about stimulus intensity available within the nociceptive system. In Experiment 2, the hand and the object were presented in separate blocks of trials. Viewing the hand shifted perceived pain levels irrespective of actual stimulus intensity, biasing responses toward 'high pain' judgments. In Experiment 3, participants saw the noxious stimulus as it approached and touched their hand or the object. Seeing the pain-inducing event counteracted the reduction in discriminability found when viewing the hand alone. These findings show that viewing the body can affect both perceptual processing of pain and responses to pain, depending on the visual context. Many factors modulate pain; our study highlights the importance of distinguishing modulations of perceptual processing from modulations of response bias. PMID- 26884133 TI - Prognostic Value of C-Reactive Protein in Resistant Hypertension. AB - BACKGROUND: C-reactive protein (CRP) is a biomarker of systemic low-grade inflammation and a cardiovascular risk predictor in several clinical conditions. However, its prognostic value has never been examined in patients with resistant hypertension. METHODS: In a prospective study, 476 patients with resistant hypertension had CRP levels measured at baseline, together with other clinical laboratory variables, including ambulatory blood pressures (BPs). Primary end points were a composite of major fatal or nonfatal cardiovascular events, all cause mortality, and cardiovascular mortality. Multiple Cox regression assessed the associations between CRP levels and end points. RESULTS: Median CRP was 3.8mg/l (interquartile range: 2.0-7.2mg/l). After a median follow-up of 9 years, 103 major cardiovascular events occurred, and 120 patients died, 62 from cardiovascular causes. Patients with CRP levels above the median value had a doubled excess risk of major cardiovascular events (95% confidence interval: 1.29 3.06; P = 0.002) and an 86% higher risk of cardiovascular death (95% confidence interval: 1.07-3.25; P = 0.029), after adjustments for potential confounders including traditional cardiovascular risk factors and ambulatory BP and dipping pattern. A high CRP equally predicted coronary (hazard ratio: 2.04; 95% confidence interval: 1.10-3.76; P = 0.023) and cerebrovascular events (hazard ratio: 2.72; 95% confidence interval: 1.30-5.67; P = 0.007). In interaction and sensitivity analyses, CRP levels were stronger predictors of worse cardiovascular outcomes in younger and obese patients, and in those with uncontrolled ambulatory BPs and with the nondipping pattern. CONCLUSIONS: In patients with resistant hypertension, elevated serum CRP levels is predictive of worse cardiovascular prognosis above and beyond other cardiovascular risk factors, including ambulatory BP levels and dipping patterns. PMID- 26884132 TI - Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex enhances working memory. AB - Neuroimaging and electrophysiological studies have unequivocally identified the dorsolateral prefrontal cortex (DLPFC) as a crucial structure for top-down control of working memory (WM) processes. By modulating the excitability of neurons in a targeted cortical area, transcranial magnetic stimulation (TMS) offers a unique way to modulate DLPFC function, opening the possibility of WM facilitation. Even though TMS neuromodulation effects over the left DLPFC have successfully improved WM performance in patients with depression and schizophrenia in a multitude of studies, raising the potential of TMS as a safe efficacious treatment for WM deficits, TMS interventions in healthy individuals have produced mixed and inconclusive results. Here, we stimulated the left DLPFC of healthy individuals using a high-frequency repetitive TMS protocol and evaluated behavioral performance in a battery of cognitive tasks. We found that TMS treatment enhanced WM performance in a verbal digit span and a visuospatial 2 back task. PMID- 26884134 TI - Does Age Matter? Association Between Usual Source of Care and Hypertension Control in the US Population: Data From NHANES 2007-2012. AB - BACKGROUND: The positive role of having a usual source of care (USOC) on the receipt of preventative services is known. However, associations between USOC and hypertension control and the differential association across age groups is unknown in the US population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Multivariable logistic regression was used to evaluate the association between having a USOC and hypertension control. The differential effect of USOC on hypertension control by age was assessed using predicted marginal effects across age groups in the multivariable logistic model. RESULTS: In adjusted analyses, those with a USOC had higher odds of hypertension control (odds ratio = 3.89, 95% confidence interval (CI): 2.15-6.98). The marginal effect of having a USOC is associated with a 30 percentage point higher probability of controlled blood pressure compared to those without a USOC (marginal probability = 0.30, 95% CI: 0.19 0.41). The marginal effect of USOC on hypertension control varied by age groups, with a statistically significantly lower marginal effect of USOC on hypertension seen among those older than 74 years of age (marginal probability = 0.27, 95% CI: 0.18-0.36) and younger than 35 years of age (marginal probability = 0.23, 95% CI: 0.14-0.33). CONCLUSION: Having a USOC is significantly associated with improved hypertension control in the US population. The variation in the association across age groups has important implications in targeting age-specific antihypertensive strategies to reduce the burden of hypertension in the US population. PMID- 26884135 TI - The Burden of Hypertension in an Oil- and Gas-Polluted Environment: A Comparative Cross-Sectional Study. AB - BACKGROUND: Evidence of positive association between traffic-related air pollution and elevated blood pressure has been published widely. However, the risk of hypertension and prolonged exposure to crude oil pollution and gas flares remains unexplored. METHODS: We recruited 2,028 residents (aged 18-80) in a cross sectional survey of both oil/gas polluted and nonpolluted communities in the Niger Delta region of Nigeria. Prevalence and risk of hypertension, anthropometric indices, lifestyle and sociodemographic factors, and cardiovascular comorbidities were examined and compared between the 2 groups. Hypertension was defined as blood pressure >=140/90mm Hg or on antihypertensive medication. Both univariate and multivariate logistic regression models were used to examine factors associated with hypertension. Model fits statistics were used to assess the parsimonious model and predictive power. RESULTS: More than one third of participants were hypertensive (37.4%). Half of the participants were from oil-polluted areas (51%). Only 15% of participants reported family history of hypertension. In the adjusted model, participants living in oil-polluted areas were almost 5 times as likely to have developed hypertension (adjusted odds ratio (aOR) = 4.85, 95% confidence interval (CI): 1.84-12.82) compared to participants in unpolluted areas. Age modifies the association between pollution status and risk of hypertension. For every 10 years increase in the age of the participants, the odds of developing hypertension increased by 108% (aOR = 2.08, 95% CI: 1.77 2.43). CONCLUSION: The results suggested that exposure to oil/gas pollution may be associated with an increased risk of hypertension. Our findings need to be further investigated in longitudinal studies. PMID- 26884136 TI - Prediction of ground motion and dynamic stress change in Baekdusan (Changbaishan) volcano caused by a North Korean nuclear explosion. AB - Strong ground motions induce large dynamic stress changes that may disturb the magma chamber of a volcano, thus accelerating the volcanic activity. An underground nuclear explosion test near an active volcano constitutes a direct treat to the volcano. This study examined the dynamic stress changes of the magma chamber of Baekdusan (Changbaishan) that can be induced by hypothetical North Korean nuclear explosions. Seismic waveforms for hypothetical underground nuclear explosions at North Korean test site were calculated by using an empirical Green's function approach based on a source-spectral model of a nuclear explosion; such a technique is efficient for regions containing poorly constrained velocity structures. The peak ground motions around the volcano were estimated from empirical strong-motion attenuation curves. A hypothetical M7.0 North Korean underground nuclear explosion may produce peak ground accelerations of 0.1684 m/s(2) in the horizontal direction and 0.0917 m/s(2) in the vertical direction around the volcano, inducing peak dynamic stress change of 67 kPa on the volcano surface and ~120 kPa in the spherical magma chamber. North Korean underground nuclear explosions with magnitudes of 5.0-7.6 may induce overpressure in the magma chamber of several tens to hundreds of kilopascals. PMID- 26884137 TI - Ion exchange at the critical point of solution. AB - A mixture of isobutyric acid (IBA)+water has an upper critical point of solution at 26.7 degrees C and an IBA concentration of 4.40M. We have determined the Langmuir isotherms for the hydroxide form of Amberlite IRN-78 resin in contact with mixtures of IBA+water at temperatures, 27.0, 29.0, 31.0 and 38.0 degrees C, respectively. The Langmuir plot at 38.0 degrees C forms a straight line. At the three lower temperatures, however, a peak in the Langmuir plot is observed for IBA concentrations in the vicinity of 4.40M. We regard this peak to be a critical effect not only because it is located close to 4.40M, but also because its height becomes more pronounced as the temperature of the isotherm approaches the critical temperature. For concentrations in the vicinity of the peak, the data indicate that the larger isobutyrate ion is rejected by the resin in favor of the smaller hydroxide ion. This reversal of the expected ion exchange reaction might be used to separate ions according to size. Using the Donnan theory of ion exchange equilibrium, we link the swelling pressure to the osmotic pressure. We show that the peak in the Langmuir plot is associated with a maximum in the "osmotic" energy. This maximum has its origin in the concentration derivative of the osmotic pressure, which goes to zero as the critical point is approached. PMID- 26884138 TI - Multiresidue analysis of endocrine-disrupting compounds and perfluorinated sulfates and carboxylic acids in sediments by ultra-high-performance liquid chromatography-tandem mass spectrometry. AB - A multiresidue analytical method for the determination of 11 perfluorinated compounds and 22 endocrine-disrupting compounds (ECDs) including 13 natural and synthetic estrogens (free and conjugated forms), 2 alkylphenols, 1 plasticiser, 2 UV-filters, 1 antimicrobial, and 2 organophosphorus compounds in sediments has been developed. Ultrasound-assisted extraction followed by solid phase extraction (SPE) with graphitized carbon black (GCB) cartridge as clean-up step were used. The extraction process yield was optimized in terms of solvent composition. Then, a 3(2) experimental design was used to optimize solvent volume and sonication time by response surface methodology, which simplifies the optimization procedure. The final extract was analyzed by ultra-high performance liquid chromatography coupled with tandem mass spectrometry. The optimized sample preparation method is simple and robust, and allows recovery of ECDs belonging to different classes in a complex matrix such as sediment. The use of GCB for SPE allowed to obtain with a single clean-up procedure excellent recoveries ranging between 75 and 110% (relative standard deviation <16%). The developed methodology has been successfully applied to the analysis of ECDs in sediments from different rivers and lakes of the Lazio Region (Italy). These analyses have shown the ubiquitous presence of chloro-substituted organophosphorus flame retardants and bisphenol A, while other analyzed compounds were occasionally found at concentration between the limit of detection and quantification. PMID- 26884139 TI - Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks. AB - Quantitative structure-property relationship (QSPR) methods are based on the hypothesis that changes in the molecular structure are reflected in changes in the observed property of the molecule. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. For the first time a quantitative structure-response relationship in electrospray ionization-mass spectrometry (ESI-MS) by means of artificial neural networks (ANN) on the group of angiotensin II receptor antagonists--sartans has been established. The investigated descriptors correspond to different properties of the analytes: polarity (logP), ionizability (pKa), surface area (solvent excluded volume) and number of proton acceptors. The influence of the instrumental parameters: methanol content in mobile phase, mobile phase pH and flow rate was also examined. Best performance showed a multilayer perceptron network with the architecture 6-3-3-1, trained with backpropagation algorithm. It showed high prediction ability on the previously unseen (test) data set with a coefficient of determination of 0.994. High prediction ability of the model would enable prediction of ESI-MS responsiveness under different conditions. This is particularly important in the method development phase. Also, prediction of responsiveness can be important in case of gradient-elution LC-MS and LC-MS/MS methods in which instrumental conditions are varied during time. Polarity, chargeability and surface area all appeared to be crucial for electrospray ionization whereby signal intensity appeared to be the result of a simultaneous influence of the molecular descriptors and their interactions. Percentage of organic phase in the mobile phase showed a positive, while flow rate showed a negative impact on signal intensity. PMID- 26884140 TI - Magnetic graphitic carbon nitride anion exchanger for specific enrichment of phosphopeptides. AB - Anion-exchange chromatography (AEX) is one of the chromatography-based methods effectively being used for phosphopeptide enrichment. However, the development of AEX materials with high specificity toward phosphopeptides is still less explored as compared to immobilized metal affinity chromatography (IMAC) or metal oxide affinity chromatography (MOAC). In this work, magnetic graphitic carbon nitride (MCN) was successfully prepared and introduced as a promising AEX candidate for phosphopeptide enrichment. Due to the extremely abundant content of nitrogen with basic functionality on the surface, this material kept excellent retention for phosphopeptides at pH as low as 1.8. Benefiting from the large binding capacity at such low pH, MCN showed remarkable specificity to capture phosphopeptides from tryptic digests of standard protein mixtures as well as nonfat milk and human serum. In addition, MCN was also applied to selective enrichment of phosphopeptides from the tryptic digests of rat brain lysate and 2576 unique phosphopeptides were successfully identified. PMID- 26884141 TI - Creating Conditions for Policy Change in National Parks: Contrasting Cases in Yellowstone and Yosemite. AB - Public agencies face significant political obstacles when they try to change long standing policies. This paper examines efforts by the U.S. National Park Service to change long-term policies in Yellowstone and Yosemite national parks. We argue that, to be successful, the agency and pro-change allies must expand the sphere of conflict to engage the support of the broader American public through positive framing, supportive science, compelling economic arguments, consistent goals, and the commitment of other institutional actors. We show that the agency is capable of creating these conditions, as in the reintroduction of wolves to Yellowstone, but we argue that this is not always the outcome, as in reducing automobile congestion in Yosemite Valley. PMID- 26884142 TI - Exploring the Capacity of Water Framework Directive Indices to Assess Ecosystem Services in Fluvial and Riparian Systems: Towards a Second Implementation Phase. AB - We explored the capacity of the biological and hydromorphological indices used in the Water Framework Directive (WFD) to assess ecosystem services by evaluating the ecological status of Spanish River Basins. This analysis relies on an exhaustive bibliography review which showed scientific evidence of the interlinkages between some ecosystem services and different hydromorphological and biological elements which have been used as indices in the WFD. Our findings indicate that, of a total of 38 ecosystem services analyzed, biological and hydromorphological indices can fully evaluate four ecosystem services. In addition, 18 ecosystem services can be partly evaluated by some of the analyzed indices, while 11 are not related with the indices. While Riparian Forest Quality was the index that was able to assess the largest number of ecosystem services (N = 12), the two indices of macrophytes offered very poor guarantees. Finally, biological indices related to diatoms and aquatic invertebrates and the Fluvial Habitat Index can be related with 7, 6, and 6 ecosystem services, respectively. Because the WFD indices currently used in Spain are not able to assess most of the ecosystem services analyzed, we suggest that there is potential to develop the second phase of the WFD implementation taking this approach into consideration. The incorporation of the ecosystem services approach into the WFD could provide the framework for assess the impacts of human activities on the quality of fluvial ecosystems and could give insights for water and watershed management in order to guarantee the delivery of multiple ecosystem services. PMID- 26884143 TI - Wildland Arson as Clandestine Resource Management: A Space-Time Permutation Analysis and Classification of Informal Fire Management Regimes in Georgia, USA. AB - Forest managers are increasingly recognizing the value of disturbance-based land management techniques such as prescribed burning. Unauthorized, "arson" fires are common in the southeastern United States where a legacy of agrarian cultural heritage persists amidst an increasingly forest-dominated landscape. This paper reexamines unauthorized fire-setting in the state of Georgia, USA from a historical ecology perspective that aims to contribute to historically informed, disturbance-based land management. A space-time permutation analysis is employed to discriminate systematic, management-oriented unauthorized fires from more arbitrary or socially deviant fire-setting behaviors. This paper argues that statistically significant space-time clusters of unauthorized fire occurrence represent informal management regimes linked to the legacy of traditional land management practices. Recent scholarship has pointed out that traditional management has actively promoted sustainable resource use and, in some cases, enhanced biodiversity often through the use of fire. Despite broad-scale displacement of traditional management during the 20th century, informal management practices may locally circumvent more formal and regionally dominant management regimes. Space-time permutation analysis identified 29 statistically significant fire regimes for the state of Georgia. The identified regimes are classified by region and land cover type and their implications for historically informed disturbance-based resource management are discussed. PMID- 26884144 TI - Worldwide Differences in Regulations of Clozapine Use. AB - Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended. PMID- 26884146 TI - Insights into the Photoelectron Spectroscopy of Chlorofluoroethenes Studied by Density-Functional and Coupled-Cluster Theories. AB - The first two ionic states of chlorofluoroethenes were studied by using both time independent and time-dependent density-functional theories. We calculated the equilibrium geometries and harmonic vibrational frequencies of 1,1-, cis-, and trans-C2H2FCl and their cations by using the B3LYP and B3PW91 functionals together with the cc-pVTZ and aug-cc-pVTZ basis sets. Franck-Condon factors were computed by the method developed in our group, in which the Duschinsky effect was treated explicitly. A new technique, named alignment transformation, followed by Euler transformations was developed to achieve the Eckart conditions. The adiabatic ionization energies were calculated by the CCSD(T) method extrapolated to the complete basis set limit. Insights into the simulated photoelectron spectra of C2H2FCl indicate that the resolutions of recent threshold photoelectron experiments are not high enough to detect individual transitions. The high-resolution photoelectron spectra of C2H2FCl are predicted for future reference. The computed adiabatic ionization energies of the three isomers of C2H2FCl are in accord with the experiments with the absolute deviations ranging from 0.004 to 0.021 eV. We suggest that the agreement between experimental and theoretical spectra should be a key criterion to judge whether a spectral assignment is reasonable. PMID- 26884145 TI - Impact of Pharmacotherapy on Cognitive Dysfunction in Patients with Multiple Sclerosis. AB - Cognitive impairment is a common symptom of multiple sclerosis (MS), adversely impacting many spheres of daily functioning. Yet the effectiveness of pharmacological interventions for cognitive impairment in MS is unclear. Clinicians and patients alike would benefit from formal guidelines regarding effective management of cognitive symptoms. We reviewed the background on the measurement, pathophysiology and risk factors for cognitive dysfunction in MS, and then examined the published clinical trials of pharmacotherapy, including both disease-modifying treatments (DMTs) and symptom-management therapies (SMTs). Our review of DMTs revealed only a single well-designed, randomized, controlled trial where intramuscular interferon (IFN)-beta1a, administered once weekly, was compared with placebo. The results showed significant benefits in terms of cognitive processing speed and memory. Less convincing but promising data have shown the potential benefits of IFN-beta1b and natalizumab. The literature on SMTs is replete with placebo-controlled, single-centre studies, with a failure to replicate initially promising results. The results for SMTs such as acetylcholinesterase inhibitors and psychostimulants are mixed. Some encouraging data show promise but not to a threshold of indication for standard clinical use. Numerous methodological factors hamper research in this area. Acknowledging the lack of firm conclusions, we argue that all DMTs are likely to benefit cognition and that, if otherwise safe, SMTs with some empirical support may be attempted at the discretion of the treating clinician. We offer some guidance on the assessment and monitoring of cognitive function to inform off-license treatment of cognitive impairment in MS patients. PMID- 26884148 TI - Fluorescence microscopy image noise reduction using a stochastically-connected random field model. AB - Fluorescence microscopy is an essential part of a biologist's toolkit, allowing assaying of many parameters like subcellular localization of proteins, changes in cytoskeletal dynamics, protein-protein interactions, and the concentration of specific cellular ions. A fundamental challenge with using fluorescence microscopy is the presence of noise. This study introduces a novel approach to reducing noise in fluorescence microscopy images. The noise reduction problem is posed as a Maximum A Posteriori estimation problem, and solved using a novel random field model called stochastically-connected random field (SRF), which combines random graph and field theory. Experimental results using synthetic and real fluorescence microscopy data show the proposed approach achieving strong noise reduction performance when compared to several other noise reduction algorithms, using quantitative metrics. The proposed SRF approach was able to achieve strong performance in terms of signal-to-noise ratio in the synthetic results, high signal to noise ratio and contrast to noise ratio in the real fluorescence microscopy data results, and was able to maintain cell structure and subtle details while reducing background and intra-cellular noise. PMID- 26884147 TI - The role of extracellular-5'-nucleotidase/CD73 in glioma peritumoural brain edema. AB - During pathological conditions, extracellular-5'-nucleotidase/CD73 can protect neurons by reducing the permeability of the blood brain barrier. In recent years, it has been demonstrated that CD73 can negatively contribute to the growth of gliomas; however, the function of CD73 in glioma blood vessels is not clear. We analysed the expression of CD73 in 72 glioma patients using immunohistochemistry and correspondingly compared the results with the Edema index (EI). We established an in vitro model of the blood-tumour barrier and analysed the expression of CD73 in vascular endothelial cells. Lastly, CD73 expression was inhibited in endothelial cells, and the effects of this inhibition on tight junction structure and transendothelial resistance were observed. Compared to normal brains, the expression of CD73 in blood vessels of glioma patients was significantly decreased, and the amount was lower in the centre of the tumour than the periphery. The proportion of CD73-positive blood vessels had a positive correlation with the EI. The expression of CD73 in the in vitro endothelial cell blood-tumour barrier model was decreased. Lastly, inhibiting CD73 was found to decrease the expression of tight junction related proteins in endothelial cells and to decrease the value of transendothelial electric resistance. The expression of CD73 in glioma blood vessels was significantly decreased, which may play a multi-functional role in decreasing the expression of tight junction related proteins of brain microvascular endothelial cells and may also increase blood tumour barrier permeability and accelerate the formation of PTBE. PMID- 26884149 TI - The roles and impacts of human hunter-gatherers in North Pacific marine food webs. AB - There is a nearly 10,000-year history of human presence in the western Gulf of Alaska, but little understanding of how human foragers integrated into and impacted ecosystems through their roles as hunter-gatherers. We present two highly resolved intertidal and nearshore food webs for the Sanak Archipelago in the eastern Aleutian Islands and use them to compare trophic roles of prehistoric humans to other species. We find that the native Aleut people played distinctive roles as super-generalist and highly-omnivorous consumers closely connected to other species. Although the human population was positioned to have strong effects, arrival and presence of Aleut people in the Sanak Archipelago does not appear associated with long-term extinctions. We simulated food web dynamics to explore to what degree introducing a species with trophic roles like those of an Aleut forager, and allowing for variable strong feeding to reflect use of hunting technology, is likely to trigger extinctions. Potential extinctions decreased when an invading omnivorous super-generalist consumer focused strong feeding on decreasing fractions of its possible resources. This study presents the first assessment of the structural roles of humans as consumers within complex ecological networks, and potential impacts of those roles and feeding behavior on associated extinctions. PMID- 26884150 TI - Effects of chronic shoulder pain on quality of life and occupational engagement in the population with chronic spinal cord injury: preparing for the best outcomes with occupational therapy. AB - Purpose To examine the implications of chronic shoulder pain on quality of life and occupational engagement in spinal cord injury (SCI). The Ecology of Human Performance Model and Self-Efficacy Theory will be used to further examine the interplay of shoulder pain, quality of life and engagement in this population. Method Analysis of literature. Results Persons with SCI have a high prevalence of shoulder pain and injury, affecting 37-84% of analysed studies; chronic pain limits occupational engagement and decreases quality of life. Remediation of pain provides improved occupational engagement, functional independence and quality of life in those with high self-efficacy and low depression. Conclusion Shoulder pain is a serious complication following SCI and the Ecology of Human Performance Model and Self-Efficacy Theory can be utilized in conjunction for a framework to evaluate, treat and prevent shoulder pain and its devastating effects on occupational engagement and quality of life in the spinal cord injured population. Thereafter, rehabilitation professionals will have a greater understanding of these interactions to serve as a guide for evaluation and intervention planning to promote optimal occupational engagement through limiting the experiences of occupational injustices for those with SCI and shoulder pain. Implications for Rehabilitation Musculoskeletal pain at the shoulder joint and depression are common complications following spinal cord injury that limit occupational engagement and decrease quality of life. To increase engagement and quality of life in this population, treatments need to address all factors including the under-lying psychosocial instead of task and environment modification alone. The Ecology of Human Performance Model and Self-efficacy Theory are effective frameworks that can be used for evaluation, treatment planning and outcome measurement to maximize occupational engagement and quality of life. PMID- 26884151 TI - Electron-lattice interactions strongly renormalize the charge-transfer energy in the spin-chain cuprate Li2CuO2. AB - Strongly correlated insulators are broadly divided into two classes: Mott-Hubbard insulators, where the insulating gap is driven by the Coulomb repulsion U on the transition-metal cation, and charge-transfer insulators, where the gap is driven by the charge-transfer energy Delta between the cation and the ligand anions. The relative magnitudes of U and Delta determine which class a material belongs to, and subsequently the nature of its low-energy excitations. These energy scales are typically understood through the local chemistry of the active ions. Here we show that the situation is more complex in the low-dimensional charge-transfer insulator Li2CuO2, where Delta has a large non-electronic component. Combining resonant inelastic X-ray scattering with detailed modelling, we determine how the elementary lattice, charge, spin and orbital excitations are entangled in this material. This results in a large lattice-driven renormalization of Delta, which significantly reshapes the fundamental electronic properties of Li2CuO2. PMID- 26884152 TI - Midbrain auditory selectivity to natural sounds. AB - This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation-sonar vocalizations-offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal directed orienting behaviors. PMID- 26884153 TI - Tailoring nanoparticle designs to target cancer based on tumor pathophysiology. AB - Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient's disease state to achieve optimal diagnostic and therapeutic outcomes. PMID- 26884154 TI - The archaeal Ced system imports DNA. AB - The intercellular transfer of DNA is a phenomenon that occurs in all domains of life and is a major driving force of evolution. Upon UV-light treatment, cells of the crenarchaeal genus Sulfolobus express Ups pili, which initiate cell aggregate formation. Within these aggregates, chromosomal DNA, which is used for the repair of DNA double-strand breaks, is exchanged. Because so far no clear homologs of bacterial DNA transporters have been identified among the genomes of Archaea, the mechanisms of archaeal DNA transport have remained a puzzling and underinvestigated topic. Here we identify saci_0568 and saci_0748, two genes from Sulfolobus acidocaldarius that are highly induced upon UV treatment, encoding a transmembrane protein and a membrane-bound VirB4/HerA homolog, respectively. DNA transfer assays showed that both proteins are essential for DNA transfer between Sulfolobus cells and act downstream of the Ups pili system. Our results moreover revealed that the system is involved in the import of DNA rather than the export. We therefore propose that both Saci_0568 and Saci_0748 are part of a previously unidentified DNA importer. Given the fact that we found this transporter system to be widely spread among the Crenarchaeota, we propose to name it the Crenarchaeal system for exchange of DNA (Ced). In this study we have for the first time to our knowledge described an archaeal DNA transporter. PMID- 26884155 TI - Marine anoxia and delayed Earth system recovery after the end-Permian extinction. AB - Delayed Earth system recovery following the end-Permian mass extinction is often attributed to severe ocean anoxia. However, the extent and duration of Early Triassic anoxia remains poorly constrained. Here we use paired records of uranium concentrations ([U]) and (238)U/(235)U isotopic compositions (delta(238)U) of Upper Permian-Upper Triassic marine limestones from China and Turkey to quantify variations in global seafloor redox conditions. We observe abrupt decreases in [U] and delta(238)U across the end-Permian extinction horizon, from ~3 ppm and 0.150/00 to ~0.3 ppm and -0.770/00, followed by a gradual return to preextinction values over the subsequent 5 million years. These trends imply a factor of 100 increase in the extent of seafloor anoxia and suggest the presence of a shallow oxygen minimum zone (OMZ) that inhibited the recovery of benthic animal diversity and marine ecosystem function. We hypothesize that in the Early Triassic oceans characterized by prolonged shallow anoxia that may have impinged onto continental shelves-global biogeochemical cycles and marine ecosystem structure became more sensitive to variation in the position of the OMZ. Under this hypothesis, the Middle Triassic decline in bottom water anoxia, stabilization of biogeochemical cycles, and diversification of marine animals together reflect the development of a deeper and less extensive OMZ, which regulated Earth system recovery following the end-Permian catastrophe. PMID- 26884156 TI - Single-molecule imaging reveals the mechanism of Exo1 regulation by single stranded DNA binding proteins. AB - Exonuclease 1 (Exo1) is a 5'->3' exonuclease and 5'-flap endonuclease that plays a critical role in multiple eukaryotic DNA repair pathways. Exo1 processing at DNA nicks and double-strand breaks creates long stretches of single-stranded DNA, which are rapidly bound by replication protein A (RPA) and other single-stranded DNA binding proteins (SSBs). Here, we use single-molecule fluorescence imaging and quantitative cell biology approaches to reveal the interplay between Exo1 and SSBs. Both human and yeast Exo1 are processive nucleases on their own. RPA rapidly strips Exo1 from DNA, and this activity is dependent on at least three RPA-encoded single-stranded DNA binding domains. Furthermore, we show that ablation of RPA in human cells increases Exo1 recruitment to damage sites. In contrast, the sensor of single-stranded DNA complex 1-a recently identified human SSB that promotes DNA resection during homologous recombination-supports processive resection by Exo1. Although RPA rapidly turns over Exo1, multiple cycles of nuclease rebinding at the same DNA site can still support limited DNA processing. These results reveal the role of single-stranded DNA binding proteins in controlling Exo1-catalyzed resection with implications for how Exo1 is regulated during DNA repair in eukaryotic cells. PMID- 26884157 TI - A highly precise and portable genome engineering method allows comparison of mutational effects across bacterial species. AB - Currently available tools for multiplex bacterial genome engineering are optimized for a few laboratory model strains, demand extensive prior modification of the host strain, and lead to the accumulation of numerous off-target modifications. Building on prior development of multiplex automated genome engineering (MAGE), our work addresses these problems in a single framework. Using a dominant-negative mutant protein of the methyl-directed mismatch repair (MMR) system, we achieved a transient suppression of DNA repair in Escherichia coli, which is necessary for efficient oligonucleotide integration. By integrating all necessary components into a broad-host vector, we developed a new workflow we term pORTMAGE. It allows efficient modification of multiple loci, without any observable off-target mutagenesis and prior modification of the host genome. Because of the conserved nature of the bacterial MMR system, pORTMAGE simultaneously allows genome editing and mutant library generation in other biotechnologically and clinically relevant bacterial species. Finally, we applied pORTMAGE to study a set of antibiotic resistance-conferring mutations in Salmonella enterica and E. coli. Despite over 100 million y of divergence between the two species, mutational effects remained generally conserved. In sum, a single transformation of a pORTMAGE plasmid allows bacterial species of interest to become an efficient host for genome engineering. These advances pave the way toward biotechnological and therapeutic applications. Finally, pORTMAGE allows systematic comparison of mutational effects and epistasis across a wide range of bacterial species. PMID- 26884158 TI - Conserved rates and patterns of transcription errors across bacterial growth states and lifestyles. AB - Errors that occur during transcription have received much less attention than the mutations that occur in DNA because transcription errors are not heritable and usually result in a very limited number of altered proteins. However, transcription error rates are typically several orders of magnitude higher than the mutation rate. Also, individual transcripts can be translated multiple times, so a single error can have substantial effects on the pool of proteins. Transcription errors can also contribute to cellular noise, thereby influencing cell survival under stressful conditions, such as starvation or antibiotic stress. Implementing a method that captures transcription errors genome-wide, we measured the rates and spectra of transcription errors in Escherichia coli and in endosymbionts for which mutation and/or substitution rates are greatly elevated over those of E. coli Under all tested conditions, across all species, and even for different categories of RNA sequences (mRNA and rRNAs), there were no significant differences in rates of transcription errors, which ranged from 2.3 * 10(-5) per nucleotide in mRNA of the endosymbiont Buchnera aphidicola to 5.2 * 10(-5) per nucleotide in rRNA of the endosymbiont Carsonella ruddii The similarity of transcription error rates in these bacterial endosymbionts to that in E. coli (4.63 * 10(-5) per nucleotide) is all the more surprising given that genomic erosion has resulted in the loss of transcription fidelity factors in both Buchnera and Carsonella. PMID- 26884159 TI - Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA. AB - In an environment with easy access to highly palatable and energy-dense food, food-related cues drive food-seeking regardless of satiety, an effect that can lead to obesity. The ventral tegmental area (VTA) and its mesolimbic projections are critical structures involved in the learning of environmental cues used to predict motivationally relevant outcomes. Priming effects of food-related advertising and consumption of palatable food can drive food intake. However, the mechanism by which this effect occurs, and whether these priming effects last days after consumption, is unknown. Here, we demonstrate that short-term consumption of palatable food can prime future food approach behaviors and food intake. This effect is mediated by the strengthening of excitatory synaptic transmission onto dopamine neurons that is initially offset by a transient increase in endocannabinoid tone, but lasts days after an initial 24-h exposure to sweetened high-fat food (SHF). This enhanced synaptic strength is mediated by a long-lasting increase in excitatory synaptic density onto VTA dopamine neurons. Administration of insulin into the VTA, which suppresses excitatory synaptic transmission onto dopamine neurons, can abolish food approach behaviors and food intake observed days after 24-h access to SHF. These results suggest that even a short-term exposure to palatable foods can drive future feeding behavior by "rewiring" mesolimbic dopamine neurons. PMID- 26884160 TI - Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD. AB - The Escherichia coli Min system self-organizes into a cell-pole to cell-pole oscillator on the membrane to prevent divisions at the cell poles. Reconstituting the Min system on a lipid bilayer has contributed to elucidating the oscillatory mechanism. However, previous in vitro patterns were attained with protein densities on the bilayer far in excess of those in vivo and failed to recapitulate the standing wave oscillations observed in vivo. Here we studied Min protein patterning at limiting MinD concentrations reflecting the in vivo conditions. We identified "burst" patterns--radially expanding and imploding binding zones of MinD, accompanied by a peripheral ring of MinE. Bursts share several features with the in vivo dynamics of the Min system including standing wave oscillations. Our data support a patterning mechanism whereby the MinD-to MinE ratio on the membrane acts as a toggle switch: recruiting and stabilizing MinD on the membrane when the ratio is high and releasing MinD from the membrane when the ratio is low. Coupling this toggle switch behavior with MinD depletion from the cytoplasm drives a self-organized standing wave oscillator. PMID- 26884161 TI - A virus of hyperthermophilic archaea with a unique architecture among DNA viruses. AB - Viruses package their genetic material in diverse ways. Most known strategies include encapsulation of nucleic acids into spherical or filamentous virions with icosahedral or helical symmetry, respectively. Filamentous viruses with dsDNA genomes are currently associated exclusively with Archaea. Here, we describe a filamentous hyperthermophilic archaeal virus, Pyrobaculum filamentous virus 1 (PFV1), with a type of virion organization not previously observed in DNA viruses. The PFV1 virion, 400 +/- 20 * 32 +/- 3 nm, contains an envelope and an inner core consisting of two structural units: a rod-shaped helical nucleocapsid formed of two 14-kDa major virion proteins and a nucleocapsid-encompassing protein sheath composed of a single major virion protein of 18 kDa. The virion organization of PFV1 is superficially similar to that of negative-sense RNA viruses of the family Filoviridae, including Ebola virus and Marburg virus. The linear dsDNA of PFV1 carries 17,714 bp, including 60-bp-long terminal inverted repeats, and contains 39 predicted ORFs, most of which do not show similarities to sequences in public databases. PFV1 is a lytic virus that completely disrupts the host cell membrane at the end of the infection cycle. PMID- 26884162 TI - The light chains of kinesin-1 are autoinhibited. AB - The light chains (KLCs) of the microtubule motor kinesin-1 bind cargoes and regulate its activity. Through their tetratricopeptide repeat domain (KLC(TPR)), they can recognize short linear peptide motifs found in many cargo proteins characterized by a central tryptophan flanked by aspartic/glutamic acid residues (W-acidic). Using a fluorescence resonance energy transfer biosensor in combination with X-ray crystallographic, biochemical, and biophysical approaches, we describe how an intramolecular interaction between the KLC2(TPR) domain and a conserved peptide motif within an unstructured region of the molecule, partly occludes the W-acidic binding site on the TPR domain. Cargo binding displaces this interaction, effecting a global conformational change in KLCs resulting in a more extended conformation. Thus, like the motor-bearing kinesin heavy chains, KLCs exist in a dynamic conformational state that is regulated by self interaction and cargo binding. We propose a model by which, via this molecular switch, W-acidic cargo binding regulates the activity of the holoenzyme. PMID- 26884163 TI - How structural adaptability exists alongside HLA-A2 bias in the human alphabeta TCR repertoire. AB - How T-cell receptors (TCRs) can be intrinsically biased toward MHC proteins while simultaneously display the structural adaptability required to engage diverse ligands remains a controversial puzzle. We addressed this by examining alphabeta TCR sequences and structures for evidence of physicochemical compatibility with MHC proteins. We found that human TCRs are enriched in the capacity to engage a polymorphic, positively charged "hot-spot" region that is almost exclusive to the alpha1-helix of the common human class I MHC protein, HLA-A*0201 (HLA-A2). TCR binding necessitates hot-spot burial, yielding high energetic penalties that must be offset via complementary electrostatic interactions. Enrichment of negative charges in TCR binding loops, particularly the germ-line loops encoded by the TCR Valpha and Vbeta genes, provides this capacity and is correlated with restricted positioning of TCRs over HLA-A2. Notably, this enrichment is absent from antibody genes. The data suggest a built-in TCR compatibility with HLA-A2 that biases receptors toward, but does not compel, particular binding modes. Our findings provide an instructional example for how structurally pliant MHC biases can be encoded within TCRs. PMID- 26884164 TI - Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. AB - The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment. PMID- 26884165 TI - Crossover from metal to insulator in dense lithium-rich compound CLi4. AB - At room environment, all materials can be classified as insulators or metals or in-between semiconductors, by judging whether they are capable of conducting the flow of electrons. One can expect an insulator to convert into a metal and to remain in this state upon further compression, i.e., pressure-induced metallization. Some exceptions were reported recently in elementary metals such as all of the alkali metals and heavy alkaline earth metals (Ca, Sr, and Ba). Here we show that a compound of CLi4 becomes progressively less conductive and eventually insulating upon compression based on ab initio density-functional theory calculations. An unusual path with pressure is found for the phase transition from metal to semimetal, to semiconductor, and eventually to insulator. The Fermi surface filling parameter is used to describe such an antimetallization process. PMID- 26884166 TI - New tools for studying microglia in the mouse and human CNS. AB - The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease. PMID- 26884167 TI - The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function. AB - The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting "Rag-5xfAD" mice exhibit a greater than twofold increase in beta-amyloid (Abeta) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Abeta clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive-innate immunity cross talk and accelerated disease progression. PMID- 26884168 TI - Selection favors incompatible signaling in bacteria. PMID- 26884169 TI - Social wasps promote social behavior in Saccharomyces spp. PMID- 26884171 TI - MEKK2 mediates an alternative beta-catenin pathway that promotes bone formation. AB - Proper tuning of beta-catenin activity in osteoblasts is required for bone homeostasis, because both increased and decreased beta-catenin activity have pathologic consequences. In the classical pathway for beta-catenin activation, stimulation with WNT ligands suppresses constitutive phosphorylation of beta catenin by glycogen synthase kinase 3beta, preventing beta-catenin ubiquitination and proteasomal degradation. Here, we have found that mitogen-activated protein kinase kinase kinase 2 (MAP3K2 or MEKK2) mediates an alternative pathway for beta catenin activation in osteoblasts that is distinct from the canonical WNT pathway. FGF2 activates MEKK2 to phosphorylate beta-catenin at serine 675, promoting recruitment of the deubiquitinating enzyme, ubiquitin-specific peptidase 15 (USP15). USP15 in turn prevents the basal turnover of beta-catenin by inhibiting its ubiquitin-dependent proteasomal degradation, thereby enhancing WNT signaling. Analysis of MEKK2-deficient mice and genetic interaction studies between Mekk2- and beta-catenin-null alleles confirm that this pathway is an important physiologic regulator of bone mass in vivo. Thus, an FGF2/MEKK2 pathway mediates an alternative nonclassical pathway for beta-catenin activation, and this pathway is a key regulator of bone formation by osteoblasts. PMID- 26884170 TI - Gene control of tyrosine kinase TIE2 and vascular manifestations of infections. AB - Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection. PMID- 26884172 TI - A protein constructed de novo enables cell growth by altering gene regulation. AB - Recent advances in protein design rely on rational and computational approaches to create novel sequences that fold and function. In contrast, natural systems selected functional proteins without any design a priori. In an attempt to mimic nature, we used large libraries of novel sequences and selected for functional proteins that rescue Escherichia coli cells in which a conditionally essential gene has been deleted. In this way, the de novo protein SynSerB3 was selected as a rescuer of cells in which serB, which encodes phosphoserine phosphatase, an enzyme essential for serine biosynthesis, was deleted. However, SynSerB3 does not rescue the deleted activity by catalyzing hydrolysis of phosphoserine. Instead, SynSerB3 up-regulates hisB, a gene encoding histidinol phosphate phosphatase. This endogenous E. coli phosphatase has promiscuous activity that, when overexpressed, compensates for the deletion of phosphoserine phosphatase. Thus, the de novo protein SynSerB3 rescues the deletion of serB by altering the natural regulation of the His operon. PMID- 26884173 TI - CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks. AB - Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force. Here, we demonstrate a mechanism by which Gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops present in Ig-type CnaA domains. Using single-molecule force spectroscopy, we find that these loops of the pilus subunit SpaA of the SpaA-type pilus from Corynebacterium diphtheriae and FimA of the type 2 pilus from Actinomyces oris unfold and extend at forces that are the highest yet reported for globular proteins. Loop refolding is limited by the hydrophobic collapse of the polypeptide and occurs in milliseconds. Remarkably, both SpaA and FimA initially refold to mechanically weaker intermediates that recover strength with time or ligand binding. Based on the high force extensibility, CnaA-containing pili can dissipate ~28-fold as much energy compared with their inextensible counterparts before reaching forces sufficient to cleave covalent bonds. We propose that efficient mechanical energy dissipation is key for sustained bacterial attachment against mechanical perturbations. PMID- 26884174 TI - A Late Paleozoic climate window of opportunity. PMID- 26884175 TI - Arabidopsis type B cytokinin response regulators ARR1, ARR10, and ARR12 negatively regulate plant responses to drought. AB - In this study, we used a loss-of-function approach to elucidate the functions of three Arabidopsis type B response regulators (ARRs)--namely ARR1, ARR10, and ARR12--in regulating the Arabidopsis plant responses to drought. The arr1,10,12 triple mutant showed a significant increase in drought tolerance versus WT plants, as indicated by its higher relative water content and survival rate on drying soil. This enhanced drought tolerance of arr1,10,12 plants can be attributed to enhanced cell membrane integrity, increased anthocyanin biosynthesis, abscisic acid (ABA) hypersensitivity, and reduced stomatal aperture, but not to altered stomatal density. Further drought-tolerance tests of lower-order double and single mutants indicated that ARR1, ARR10, and ARR12 negatively and redundantly control plant responses to drought, with ARR1 appearing to bear the most critical function among the three proteins. In agreement with these findings, a comparative genome-wide analysis of the leaves of arr1,10,12 and WT plants under both normal and dehydration conditions suggested a cytokinin (CK) signaling-mediated network controlling plant adaptation to drought via many dehydration/drought- and/or ABA-responsive genes that can provide osmotic adjustment and protection to cellular and membrane structures. Expression of all three ARR genes was repressed by dehydration and ABA treatments, inferring that plants down-regulate these genes as an adaptive mechanism to survive drought. Collectively, our results demonstrate that repression of CK response, and thus CK signaling, is one of the strategies plants use to cope with water deficit, providing novel insight for the design of drought tolerant plants by genetic engineering. PMID- 26884176 TI - Dispelling the effects of a sorceress in enzyme catalysis. PMID- 26884177 TI - Illuminating structural proteins in viral "dark matter" with metaproteomics. AB - Viruses are ecologically important, yet environmental virology is limited by dominance of unannotated genomic sequences representing taxonomic and functional "viral dark matter." Although recent analytical advances are rapidly improving taxonomic annotations, identifying functional dark matter remains problematic. Here, we apply paired metaproteomics and dsDNA-targeted metagenomics to identify 1,875 virion-associated proteins from the ocean. Over one-half of these proteins were newly functionally annotated and represent abundant and widespread viral metagenome-derived protein clusters (PCs). One primarily unannotated PC dominated the dataset, but structural modeling and genomic context identified this PC as a previously unidentified capsid protein from multiple uncultivated tailed virus families. Furthermore, four of the five most abundant PCs in the metaproteome represent capsid proteins containing the HK97-like protein fold previously found in many viruses that infect all three domains of life. The dominance of these proteins within our dataset, as well as their global distribution throughout the world's oceans and seas, supports prior hypotheses that this HK97-like protein fold is the most abundant biological structure on Earth. Together, these culture independent analyses improve virion-associated protein annotations, facilitate the investigation of proteins within natural viral communities, and offer a high throughput means of illuminating functional viral dark matter. PMID- 26884179 TI - Correction for Upadhyay et al., Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain. PMID- 26884178 TI - Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect. AB - Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins. PMID- 26884180 TI - Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-sigma factor. AB - The BvgAS phosphorelay regulates ~10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. Here, we characterize a regulatory node involving a type III secretion system (T3SS)-exported protein, BtrA, and demonstrate its role in determining fundamental differences in T3SS phenotypes among Bordetella species. We show that BtrA binds and antagonizes BtrS, a BvgAS-regulated extracytoplasmic function (ECF) sigma factor, to couple the secretory activity of the T3SS apparatus to gene expression. In B. bronchiseptica, a remarkable spectrum of expression states can be resolved by manipulating btrA, encompassing over 80 BtrA-activated loci that include genes encoding toxins, adhesins, and other cell surface proteins, and over 200 BtrA-repressed genes that encode T3SS apparatus components, secretion substrates, the BteA effector, and numerous additional factors. In B. pertussis, BtrA retains activity as a BtrS antagonist and exerts tight negative control over T3SS genes. Most importantly, deletion of btrA in B. pertussis revealed T3SS-mediated, BteA-dependent cytotoxicity, which had previously eluded detection. This effect was observed in laboratory strains and in clinical isolates from a recent California pertussis epidemic. We propose that the BtrA BtrS regulatory node determines subspecies-specific differences in T3SS expression among Bordetella species and that B. pertussis is capable of expressing a full range of T3SS-dependent phenotypes in the presence of appropriate contextual cues. PMID- 26884181 TI - Phagocytosis genes nonautonomously promote developmental cell death in the Drosophila ovary. AB - Programmed cell death (PCD) is usually considered a cell-autonomous suicide program, synonymous with apoptosis. Recent research has revealed that PCD is complex, with at least a dozen cell death modalities. Here, we demonstrate that the large-scale nonapoptotic developmental PCD in the Drosophila ovary occurs by an alternative cell death program where the surrounding follicle cells nonautonomously promote death of the germ line. The phagocytic machinery of the follicle cells, including Draper, cell death abnormality (Ced)-12, and c-Jun N terminal kinase (JNK), is essential for the death and removal of germ-line derived nurse cells during late oogenesis. Cell death events including acidification, nuclear envelope permeabilization, and DNA fragmentation of the nurse cells are impaired when phagocytosis is inhibited. Moreover, elimination of a small subset of follicle cells prevents nurse cell death and cytoplasmic dumping. Developmental PCD in the Drosophila ovary is an intriguing example of nonapoptotic, nonautonomous PCD, providing insight on the diversity of cell death mechanisms. PMID- 26884182 TI - First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer. AB - Improved understanding of the relationship among structure, dynamics, and function for the enzyme phenylalanine hydroxylase (PAH) can lead to needed new therapies for phenylketonuria, the most common inborn error of amino acid metabolism. PAH is a multidomain homo-multimeric protein whose conformation and multimerization properties respond to allosteric activation by the substrate phenylalanine (Phe); the allosteric regulation is necessary to maintain Phe below neurotoxic levels. A recently introduced model for allosteric regulation of PAH involves major domain motions and architecturally distinct PAH tetramers [Jaffe EK, Stith L, Lawrence SH, Andrake M, Dunbrack RL, Jr (2013) Arch Biochem Biophys 530(2):73-82]. Herein, we present, to our knowledge, the first X-ray crystal structure for a full-length mammalian (rat) PAH in an autoinhibited conformation. Chromatographic isolation of a monodisperse tetrameric PAH, in the absence of Phe, facilitated determination of the 2.9 A crystal structure. The structure of full-length PAH supersedes a composite homology model that had been used extensively to rationalize phenylketonuria genotype-phenotype relationships. Small-angle X-ray scattering (SAXS) confirms that this tetramer, which dominates in the absence of Phe, is different from a Phe-stabilized allosterically activated PAH tetramer. The lack of structural detail for activated PAH remains a barrier to complete understanding of phenylketonuria genotype-phenotype relationships. Nevertheless, the use of SAXS and X-ray crystallography together to inspect PAH structure provides, to our knowledge, the first complete view of the enzyme in a tetrameric form that was not possible with prior partial crystal structures, and facilitates interpretation of a wealth of biochemical and structural data that was hitherto impossible to evaluate. PMID- 26884183 TI - Cognitive fatigue influences students' performance on standardized tests. AB - Using test data for all children attending Danish public schools between school years 2009/10 and 2012/13, we examine how the time of the test affects performance. Test time is determined by the weekly class schedule and computer availability at the school. We find that, for every hour later in the day, test performance decreases by 0.9% of an SD (95% CI, 0.7-1.0%). However, a 20- to 30 minute break improves average test performance by 1.7% of an SD (95% CI, 1.2 2.2%). These findings have two important policy implications: First, cognitive fatigue should be taken into consideration when deciding on the length of the school day and the frequency and duration of breaks throughout the day. Second, school accountability systems should control for the influence of external factors on test scores. PMID- 26884184 TI - Load-dependent destabilization of the gamma-rotor shaft in FOF1 ATP synthase revealed by hydrogen/deuterium-exchange mass spectrometry. AB - FoF1 is a membrane-bound molecular motor that uses proton-motive force (PMF) to drive the synthesis of ATP from ADP and Pi. Reverse operation generates PMF via ATP hydrolysis. Catalysis in either direction involves rotation of the gammaepsilon shaft that connects the alpha3beta3 head and the membrane-anchored cn ring. X-ray crystallography and other techniques have provided insights into the structure and function of FoF1 subcomplexes. However, interrogating the conformational dynamics of intact membrane-bound FoF1 during rotational catalysis has proven to be difficult. Here, we use hydrogen/deuterium exchange mass spectrometry to probe the inner workings of FoF1 in its natural membrane-bound state. A pronounced destabilization of the gamma C-terminal helix during hydrolysis-driven rotation was observed. This behavior is attributed to torsional stress in gamma, arising from gamma???alpha3beta3 interactions that cause resistance during gamma rotation within the apical bearing. Intriguingly, we find that destabilization of gamma occurs only when FoF1 operates against a PMF induced torque; the effect disappears when PMF is eliminated by an uncoupler. This behavior resembles the properties of automotive engines, where bearings inflict greater forces on the crankshaft when operated under load than during idling. PMID- 26884185 TI - Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma. AB - PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2(E824)*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57(KIP2)). This down regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator. PMID- 26884186 TI - Reply to Martincorena et al.: Evidence for constrained positive selection of cancer mutations in normal skin is lacking. PMID- 26884187 TI - Constrained positive selection on cancer mutations in normal skin. PMID- 26884188 TI - The effect of rights-based fisheries management on risk taking and fishing safety. AB - Commercial fishing is a dangerous occupation despite decades of regulatory initiatives aimed at making it safer. We posit that rights-based fisheries management (the individual allocation of fishing quota to vessels or fishing entities, also called catch shares) can improve safety by solving many of the problems associated with the competitive race to fish experienced in fisheries around the world. The competitive nature of such fisheries results in risky behavior such as fishing in poor weather, overloading vessels with fishing gear, and neglecting maintenance. Although not necessarily intended to address safety issues, catch shares eliminate many of the economic incentives to fish as rapidly as possible. We develop a dataset and methods to empirically evaluate the effects of the adoption of catch shares management on a particularly risky type of behavior: the propensity to fish in stormy weather. After catch shares was implemented in an economically important US West Coast fishery, a fisherman's probability of taking a fishing trip in high wind conditions decreased by 82% compared with only 31% in the former race to fish fishery. Overall, catch shares caused the average annual rate of fishing on high wind days to decrease by 79%. These results are evidence that institutional changes can significantly reduce individual, voluntary risk exposure and result in safer fisheries. PMID- 26884189 TI - Correction for Riedl et al., Metabolic connectivity mapping reveals effective connectivity in the resting human brain. PMID- 26884190 TI - Correction for Lai et al., Sequence, structure, and cooperativity in folding of elementary protein structural motifs. PMID- 26884191 TI - Mechanism of a cytosolic O-glycosyltransferase essential for the synthesis of a bacterial adhesion protein. AB - O-glycosylation of Ser and Thr residues is an important process in all organisms, which is only poorly understood. Such modification is required for the export and function of adhesin proteins that mediate the attachment of pathogenic Gram positive bacteria to host cells. Here, we have analyzed the mechanism by which the cytosolic O-glycosyltransferase GtfA/B of Streptococcus gordonii modifies the Ser/Thr-rich repeats of adhesin. The enzyme is a tetramer containing two molecules each of GtfA and GtfB. The two subunits have the same fold, but only GtfA contains an active site, whereas GtfB provides the primary binding site for adhesin. During a first phase of glycosylation, the conformation of GtfB is restrained by GtfA to bind substrate with unmodified Ser/Thr residues. In a slow second phase, GtfB recognizes residues that are already modified with N acetylglucosamine, likely by converting into a relaxed conformation in which one interface with GtfA is broken. These results explain how the glycosyltransferase modifies a progressively changing substrate molecule. PMID- 26884192 TI - Probing the promiscuity of ent-kaurene oxidases via combinatorial biosynthesis. AB - The substrate specificity of enzymes from natural products' metabolism is a topic of considerable interest, with potential biotechnological use implicit in the discovery of promiscuous enzymes. However, such studies are often limited by the availability of substrates and authentic standards for identification of the resulting products. Here, a modular metabolic engineering system is used in a combinatorial biosynthetic approach toward alleviating this restriction. In particular, for studies of the multiply reactive cytochrome P450, ent-kaurene oxidase (KO), which is involved in production of the diterpenoid plant hormone gibberellin. Many, but not all, plants make a variety of related diterpenes, whose structural similarity to ent-kaurene makes them potential substrates for KO. Use of combinatorial biosynthesis enabled analysis of more than 20 such potential substrates, as well as structural characterization of 12 resulting unknown products, providing some insight into the underlying structure-function relationships. These results highlight the utility of this approach for investigating the substrate specificity of enzymes from complex natural products' biosynthesis. PMID- 26884193 TI - Proteomics of HCV virions reveals an essential role for the nucleoporin Nup98 in virus morphogenesis. AB - Hepatitis C virus (HCV) is a unique enveloped virus that assembles as a hybrid lipoviral particle by tightly interacting with host lipoproteins. As a result, HCV virions display a characteristic low buoyant density and a deceiving coat, with host-derived apolipoproteins masking viral epitopes. We previously described methods to produce high-titer preparations of HCV particles with tagged envelope glycoproteins that enabled ultrastructural analysis of affinity-purified virions. Here, we performed proteomics studies of HCV isolated from culture media of infected hepatoma cells to define viral and host-encoded proteins associated with mature virions. Using two different affinity purification protocols, we detected four viral and 46 human cellular proteins specifically copurifying with extracellular HCV virions. We determined the C terminus of the mature capsid protein and reproducibly detected low levels of the viral nonstructural protein, NS3. Functional characterization of virion-associated host factors by RNAi identified cellular proteins with either proviral or antiviral roles. In particular, we discovered a novel interaction between HCV capsid protein and the nucleoporin Nup98 at cytosolic lipid droplets that is important for HCV propagation. These results provide the first comprehensive view to our knowledge of the protein composition of HCV and new insights into the complex virus-host interactions underlying HCV infection. PMID- 26884194 TI - Host immunity shapes the impact of climate changes on the dynamics of parasite infections. AB - Global climate change is predicted to alter the distribution and dynamics of soil transmitted helminth infections, and yet host immunity can also influence the impact of warming on host-parasite interactions and mitigate the long-term effects. We used time-series data from two helminth species of a natural herbivore and investigated the contribution of climate change and immunity on the long-term and seasonal dynamics of infection. We provide evidence that climate warming increases the availability of infective stages of both helminth species and the proportional increase in the intensity of infection for the helminth not regulated by immunity. In contrast, there is no significant long-term positive trend in the intensity for the immune-controlled helminth, as immunity reduces the net outcome of climate on parasite dynamics. Even so, hosts experienced higher infections of this helminth at an earlier age during critical months in the warmer years. Immunity can alleviate the expected long-term effect of climate on parasite infections but can also shift the seasonal peak of infection toward the younger individuals. PMID- 26884196 TI - Correction for Strickland et al., Event representations constrain the structure of language: Sign language as a window into universally accessible linguistic biases. PMID- 26884195 TI - Kinetic model of the aggregation of alpha-synuclein provides insights into prion like spreading. AB - The protein alpha-synuclein (alphaS) self-assembles into small oligomeric species and subsequently into amyloid fibrils that accumulate and proliferate during the development of Parkinson's disease. However, the quantitative characterization of the aggregation and spreading of alphaS remains challenging to achieve. Previously, we identified a conformational conversion step leading from the initially formed oligomers to more compact oligomers preceding fibril formation. Here, by a combination of single-molecule fluorescence measurements and kinetic analysis, we find that the reaction in solution involves two unimolecular structural conversion steps, from the disordered to more compact oligomers and then to fibrils, which can elongate by further monomer addition. We have obtained individual rate constants for these key microscopic steps by applying a global kinetic analysis to both the decrease in the concentration of monomeric protein molecules and the increase in oligomer concentrations over a 0.5-140-uM range of alphaS. The resulting explicit kinetic model of alphaS aggregation has been used to quantitatively explore seeding the reaction by either the compact oligomers or fibrils. Our predictions reveal that, although fibrils are more effective at seeding than oligomers, very high numbers of seeds of either type, of the order of 10(4), are required to achieve efficient seeding and bypass the slow generation of aggregates through primary nucleation. Complementary cellular experiments demonstrated that two orders of magnitude lower numbers of oligomers were sufficient to generate high levels of reactive oxygen species, suggesting that effective templated seeding is likely to require both the presence of template aggregates and conditions of cellular stress. PMID- 26884198 TI - Giant magneto-optical Raman effect in a layered transition metal compound. AB - We report a dramatic change in the intensity of a Raman mode with applied magnetic field, displaying a gigantic magneto-optical effect. Using the nonmagnetic layered material MoS2 as a prototype system, we demonstrate that the application of a magnetic field perpendicular to the layers produces a dramatic change in intensity for the out-of-plane vibrations of S atoms, but no change for the in-plane breathing mode. The distinct intensity variation between these two modes results from the effect of field-induced broken symmetry on Raman scattering cross-section. A quantitative analysis on the field-dependent integrated Raman intensity provides a unique method to precisely determine optical mobility. Our analysis is symmetry-based and material-independent, and thus the observations should be general and inspire a new branch of inelastic light scattering and magneto-optical applications. PMID- 26884197 TI - Conserved properties of individual Ca2+-binding sites in calmodulin. AB - Calmodulin (CaM) is a Ca(2+)-sensing protein that is highly conserved and ubiquitous in eukaryotes. In humans it is a locus of life-threatening cardiomyopathies. The primary function of CaM is to transduce Ca(2+) concentration into cellular signals by binding to a wide range of target proteins in a Ca(2+)-dependent manner. We do not fully understand how CaM performs its role as a high-fidelity signal transducer for more than 300 target proteins, but diversity among its four Ca(2+)-binding sites, called EF-hands, may contribute to CaM's functional versatility. We therefore looked at the conservation of CaM sequences over deep evolutionary time, focusing primarily on the four EF-hand motifs. Expanding on previous work, we found that CaM evolves slowly but that its evolutionary rate is substantially faster in fungi. We also found that the four EF-hands have distinguishing biophysical and structural properties that span eukaryotes. These results suggest that all eukaryotes require CaM to decode Ca(2+) signals using four specialized EF-hands, each with specific, conserved traits. In addition, we provide an extensive map of sites associated with target proteins and with human disease and correlate these with evolutionary sequence diversity. Our comprehensive evolutionary analysis provides a basis for understanding the sequence space associated with CaM function and should help guide future work on the relationship between structure, function, and disease. PMID- 26884199 TI - Infants use relative numerical group size to infer social dominance. AB - Detecting dominance relationships, within and across species, provides a clear fitness advantage because this ability helps individuals assess their potential risk of injury before engaging in a competition. Previous research has demonstrated that 10- to 13-mo-old infants can represent the dominance relationship between two agents in terms of their physical size (larger agent = more dominant), whereas younger infants fail to do so. It is unclear whether infants younger than 10 mo fail to represent dominance relationships in general, or whether they lack sensitivity to physical size as a cue to dominance. Two studies explored whether infants, like many species across the animal kingdom, use numerical group size to assess dominance relationships and whether this capacity emerges before their sensitivity to physical size. A third study ruled out an alternative explanation for our findings. Across these studies, we report that infants 6-12 mo of age use numerical group size to infer dominance relationships. Specifically, preverbal infants expect an agent from a numerically larger group to win in a right-of-way competition against an agent from a numerically smaller group. In addition, this is, to our knowledge, the first study to demonstrate that infants 6-9 mo of age are capable of understanding social dominance relations. These results demonstrate that infants' understanding of social dominance relations may be based on evolutionarily relevant cues and reveal infants' early sensitivity to an important adaptive function of social groups. PMID- 26884200 TI - Atoms of recognition in human and computer vision. AB - Discovering the visual features and representations used by the brain to recognize objects is a central problem in the study of vision. Recently, neural network models of visual object recognition, including biological and deep network models, have shown remarkable progress and have begun to rival human performance in some challenging tasks. These models are trained on image examples and learn to extract features and representations and to use them for categorization. It remains unclear, however, whether the representations and learning processes discovered by current models are similar to those used by the human visual system. Here we show, by introducing and using minimal recognizable images, that the human visual system uses features and processes that are not used by current models and that are critical for recognition. We found by psychophysical studies that at the level of minimal recognizable images a minute change in the image can have a drastic effect on recognition, thus identifying features that are critical for the task. Simulations then showed that current models cannot explain this sensitivity to precise feature configurations and, more generally, do not learn to recognize minimal images at a human level. The role of the features shown here is revealed uniquely at the minimal level, where the contribution of each feature is essential. A full understanding of the learning and use of such features will extend our understanding of visual recognition and its cortical mechanisms and will enhance the capacity of computational models to learn from visual experience and to deal with recognition and detailed image interpretation. PMID- 26884201 TI - Widespread collapse of the Ross Ice Shelf during the late Holocene. AB - The stability of modern ice shelves is threatened by atmospheric and oceanic warming. The geologic record of formerly glaciated continental shelves provides a window into the past of how ice shelves responded to a warming climate. Fields of deep (-560 m), linear iceberg furrows on the outer, western Ross Sea continental shelf record an early post-Last Glacial Maximum episode of ice-shelf collapse that was followed by continuous retreat of the grounding line for ~200 km. Runaway grounding line conditions culminated once the ice became pinned on shallow banks in the western Ross Sea. This early episode of ice-shelf collapse is not observed in the eastern Ross Sea, where more episodic grounding line retreat took place. More widespread (~280,000 km(2)) retreat of the ancestral Ross Ice Shelf occurred during the late Holocene. This event is recorded in sediment cores by a shift from terrigenous glacimarine mud to diatomaceous open marine sediment as well as an increase in radiogenic beryllium ((10)Be) concentrations. The timing of ice-shelf breakup is constrained by compound specific radiocarbon ages, the first application of this technique systematically applied to Antarctic marine sediments. Breakup initiated around 5 ka, with the ice shelf reaching its current configuration ~1.5 ka. In the eastern Ross Sea, the ice shelf retreated up to 100 km in about a thousand years. Three-dimensional thermodynamic ice-shelf/ocean modeling results and comparison with ice-core records indicate that ice-shelf breakup resulted from combined atmospheric warming and warm ocean currents impinging onto the continental shelf. PMID- 26884202 TI - Reply to Solow: Sense and nonsense in the choice of extinction priors. PMID- 26884204 TI - Correction for Kumar et al., Natural history-driven, plant-mediated RNAi-based study reveals CYP6B46's role in a nicotine-mediated antipredator herbivore defense. PMID- 26884203 TI - On Bayesian inference about extinction. PMID- 26884205 TI - Competition between anthocyanin and flavonol biosynthesis produces spatial pattern variation of floral pigments between Mimulus species. AB - Flower color patterns have long served as a model for developmental genetics because pigment phenotypes are visually striking, yet generally not required for plant viability, facilitating the genetic analysis of color and pattern mutants. The evolution of novel flower colors and patterns has played a key role in the adaptive radiation of flowering plants via their specialized interactions with different pollinator guilds (e.g., bees, butterflies, birds), motivating the search for allelic differences affecting flower color pattern in closely related plant species with different pollinators. We have identified LIGHT AREAS1 (LAR1), encoding an R2R3-MYB transcription factor, as the causal gene underlying the spatial pattern variation of floral anthocyanin pigmentation between two sister species of monkeyflower: the bumblebee-pollinated Mimulus lewisii and the hummingbird-pollinated Mimulus cardinalis. We demonstrated that LAR1 positively regulates FLAVONOL SYNTHASE (FLS), essentially eliminating anthocyanin biosynthesis in the white region (i.e., light areas) around the corolla throat of M. lewisii flowers by diverting dihydroflavonol into flavonol biosynthesis from the anthocyanin pigment pathway. FLS is preferentially expressed in the light areas of the M. lewisii flower, thus prepatterning the corolla. LAR1 expression in M. cardinalis flowers is much lower than in M. lewisii, explaining the unpatterned phenotype and recessive inheritance of the M. cardinalis allele. Furthermore, our gene-expression analysis and genetic mapping results suggest that cis-regulatory change at the LAR1 gene played a critical role in the evolution of different pigmentation patterns between the two species. PMID- 26884206 TI - Sex-specific regulation of Lgr3 in Drosophila neurons. AB - The development of sexually dimorphic morphology and the potential for sexually dimorphic behavior in Drosophila are regulated by the Fruitless (Fru) and Doublesex (Dsx) transcription factors. Several direct targets of Dsx have been identified, but direct Fru targets have not been definitively identified. We show that Drosophila leucine-rich repeat G protein-coupled receptor 3 (Lgr3) is regulated by Fru and Dsx in separate populations of neurons. Lgr3 is a member of the relaxin-receptor family and a receptor for Dilp8, necessary for control of organ growth. Lgr3 expression in the anterior central brain of males is inhibited by the B isoform of Fru, whose DNA binding domain interacts with a short region of an Lgr3 intron. Fru A and C isoform mutants had no observed effect on Lgr3 expression. The female form of Dsx (Dsx(F)) separately up- and down-regulates Lgr3 expression in distinct neurons in the abdominal ganglion through female- and male-specific Lgr3 enhancers. Excitation of neural activity in the Dsx(F)-up regulated abdominal ganglion neurons inhibits female receptivity, indicating the importance of these neurons for sexual behavior. Coordinated regulation of Lgr3 by Fru and Dsx marks a point of convergence of the two branches of the sex determination hierarchy. PMID- 26884207 TI - Cholesteryl esters stabilize human CD1c conformations for recognition by self reactive T cells. AB - Cluster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but self-antigens presented by CD1c to the T-cell receptors of these cells are poorly understood. Here we present a crystal structure of CD1c determined at 2.4 A revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known CD1c structures. Computational simulations exploring different occupancy states of the groove reenacted these different CD1c conformations and suggested cholesteryl esters (CE) and acylated steryl glycosides (ASG) as new ligand classes for CD1c. Confirming this, we show that binding of CE and ASG to CD1c enables the binding of human CD1c self-reactive T-cell receptors. Hence, human CD1c adopts different conformations dependent on ligand occupancy of its groove, with CE and ASG stabilizing CD1c conformations that provide a footprint for binding of CD1c self reactive T-cell receptors. PMID- 26884208 TI - Invisible metallic mesh. AB - A solid material possessing identical electromagnetic properties as air has yet to be found in nature. Such a medium of arbitrary shape would neither reflect nor refract light at any angle of incidence in free space. Here, we introduce nonscattering corrugated metallic wires to construct such a medium. This was accomplished by aligning the dark-state frequencies in multiple scattering channels of a single wire. Analytical solutions, full-wave simulations, and microwave measurement results on 3D printed samples show omnidirectional invisibility in any configuration. This invisible metallic mesh can improve mechanical stability, electrical conduction, and heat dissipation of a system, without disturbing the electromagnetic design. Our approach is simple, robust, and scalable to higher frequencies. PMID- 26884209 TI - AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas. AB - Patients with inoperable or unresectable pancreatic neuroendocrine tumors (NETs) have limited treatment options. These rare human tumors often express somatostatin receptors (SSTRs) and thus are clinically responsive to certain relatively stable somatostatin analogs, such as octreotide. Unfortunately, however, this tumor response is generally short-lived. Here we designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor (TNF) transgene specifically to NETs. These functional attributes of AAVP-TNF particles displaying the octreotide peptide motif (termed Oct-AAVP-TNF) were confirmed in vitro, in SSTR type 2-expressing NET cells, and in vivo using cohorts of pancreatic NET-bearing Men1 tumor-suppressor gene KO mice, a transgenic model of functioning (i.e., insulin-secreting) tumors that genetically and clinically recapitulates the human disease. Finally, preclinical imaging and therapeutic experiments with pancreatic NET-bearing mice demonstrated that Oct AAVP-TNF lowered tumor metabolism and insulin secretion, reduced tumor size, and improved mouse survival. Taken together, these proof-of-concept results establish Oct-AAVP-TNF as a strong therapeutic candidate for patients with NETs of the pancreas. More broadly, the demonstration that a known, short, biologically active motif can direct tumor targeting and receptor-mediated internalization of AAVP particles may streamline the potential utility of myriad other short peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers and perhaps many nonmalignant diseases as well. PMID- 26884210 TI - Bioactive cell-like hybrids coassembled from (glyco)dendrimersomes with bacterial membranes. AB - A library of amphiphilic Janus dendrimers including two that are fluorescent and one glycodendrimer presenting lactose were used to construct giant dendrimersomes and glycodendrimersomes. Coassembly with the components of bacterial membrane vesicles by a dehydration-rehydration process generated giant cell-like hybrid vesicles, whereas the injection of their ethanol solution into PBS produced monodisperse nanometer size assemblies. These hybrid vesicles contain transmembrane proteins including a small membrane protein, MgrB, tagged with a red fluorescent protein, lipopolysaccharides, and glycoproteins from the bacterium Escherichia coli. Incorporation of two colored fluorescent probes in each of the components allowed fluorescence microscopy to visualize and demonstrate coassembly and the incorporation of functional membrane channels. Importantly, the hybrid vesicles bind a human galectin, consistent with the display of sugar moieties from lipopolysaccharides or possibly glycosylated membrane proteins. The present coassembly method is likely to create cell-like hybrids from any biological membrane including human cells and thus may enable practical application in nanomedicine. PMID- 26884211 TI - Autotransplantation of Monkey Ear Perichondrium-Derived Progenitor Cells for Cartilage Reconstruction. AB - We recently developed a promising regenerative method based on the xenotransplantation of human cartilage progenitor cells, demonstrating self renewing elastic cartilage reconstruction with expected long-term tissue restoration. However, it remains unclear whether autotransplantation of cartilage progenitors may work by a similar principle in immunocompetent individuals. We used a nonhuman primate (monkey) model to assess the safety and efficacy of our regenerative approach because the model shares characteristics with humans in terms of biological functions, including anatomical features. First, we identified the expandable and multipotent progenitor population from monkey ear perichondrium and succeeded in inducing chondrocyte differentiation in vitro. Second, in vivo transplanted progenitor cells were capable of reconstructing elastic cartilage by xenotransplantation into an immunodeficient mouse. Finally, the autologous monkey progenitor cells were transplanted into the subcutaneous region of a craniofacial section and developed mature elastic cartilage of their own 3 months after transplantation. Furthermore, we attempted to develop a clinically relevant, noninvasive monitoring method using magnetic resonance imaging (MRI). Collectively, this report shows that the autologous transplantation of cartilage progenitors is potentially effective for reconstructing elastic cartilage. This principle will be invaluable for repairing craniofacial injuries and abnormalities in the context of plastic and reconstructive surgery. PMID- 26884213 TI - [Editorial]. PMID- 26884212 TI - Endogenous hydrogen peroxide increases biofilm formation by inducing exopolysaccharide production in Acinetobacter oleivorans DR1. AB - In this study, we investigated differentially expressed proteins in Acinetobacter oleivorans cells during planktonic and biofilm growth by using 2-dimensional gel electrophoresis combined with matrix-assisted laser desorption time-of-flight mass spectrometry. We focused on the role of oxidative stress resistance during biofilm formation using mutants defective in alkyl hydroperoxide reductase (AhpC) because its production in aged biofilms was enhanced compared to that in planktonic cells. Results obtained using an ahpC promoter-gfp reporter vector showed that aged biofilms expressed higher ahpC levels than planktonic cells at 48 h. However, at 24 h, ahpC expression was higher in planktonic cells than in biofilms. Deletion of ahpC led to a severe growth defect in rich media that was not observed in minimal media and promoted early biofilm formation through increased production of exopolysaccharide (EPS) and EPS gene expression. Increased endogenous H2O2 production in the ahpC mutant in rich media enhanced biofilm formation, and this enhancement was not observed in the presence of antioxidants. Exogenous addition of H2O2 promoted biofilm formation in wild type cells, which suggested that biofilm development is linked to defense against H2O2. Collectively, our data showed that EPS production caused by H2O2 stress enhances biofilm formation in A. oleivorans. PMID- 26884214 TI - [Diagnosis of ILD]. AB - The diagnosis of ILD is complex and needs a close collaboration between the pulmologist, the radiologist and the pathologist. However, and most importantly, the general practitioner needs to think about the possibility of ILD if a patient presents with increasing shortness of breath, dry cough and bilateral, basal crackles on lung auscultation. Further work-up by the pulmonologist may confirm and classify the ILD by a detailled patient history, lung function tests, CT scans and bronchoscopy, or even surgical lung biospies, if needed. A multidisciplinary discussion (MDD) is becoming the gold standard in diagnosing ILD and deciding about appropriate treatment, in particular regarding the novel antifibrotic therapies for IPF. PMID- 26884215 TI - [Interstitial pneumonias--Histopathological and radiological correlation]. AB - Interstitial pneumonias comprise a group of lung diseases with overlapping clinical, radiological and pathological presentations. Because of the frequently non-discriminating clinical manifestation, correlation between radiology and pathology plays an important role. Multidisciplinary discussion is of utmost importance for establishing a valid diagnosis, and is considered a gold standard in the current 2002/2013 classification of idiopathic interstitial pneumonias. In the present work, we concisely review and illustrate the typical radiological and pathological pictures diagnostic for the most common (idiopathic) interstitial pneumonias. PMID- 26884216 TI - [Idiopathic pulmonary fibrosis--Pathogenesis and therapeutic concepts]. AB - Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonias (IIP). It is characterized by progressive destruction of the normal lung architecture, finally leading to death. The pathogenesis of IPF is not completely understood but a complex interplay between environmental factors, such as smoking or viral infections, and genetic predisposition seems to be an important precondition. Repetitive micro-injuries to alveolar epithelial cells and dysregulated wound repair with impaired re-epithelialization are regarded as the initial process of IPF. This alveolar damage is followed by an uncontrolled proliferation and extracellular matrix deposition of fibroblasts, ultimately leading to distortion of the lung parenchyma. According to this "non inflammatory" pathogenic hypothesis, therapeutic approaches currently focus on anti-fibrotic compounds, which prevent or inhibit fibroblast proliferation and extracellular matrix deposition, or antagonize the effect of pro-fibrotic growth factors. PMID- 26884217 TI - [Anti-fibrotics as novel therapy for idiopathic pulmonary fibrosis]. AB - Recent studies have shown efficacy to slow the decrease of forced vital capacity in patients with idiopathic pulmonary fibrosis. This summary refers to recent anti-fibrotic medications and describes current studies, indication for treatment and side effects, as well as discusses open questions of treatment. PMID- 26884218 TI - [Sarcoidosis--a multisystem disorder with variable prognosis]. AB - Sarcoidosis is a pneumotropic granulomatous inflammatory multisystem disorder of unknown origin and heterogeneous outcome. In most cases the disease is self limited, others progress or die from organ involvement, which is often associated with extensive pulmonary scarring or relevant extrapulmonary organ involvement. Therefore, patients with sarcoidosis must be staged for multiorgan involvement. Modern treatment strategies appraise a critical awareness for the effect to side effect-ratio of long-term immunosuppressive medication. PMID- 26884219 TI - [Interstitial lung disease and connective tissue diseases]. AB - Lung involvement in rheumatologic diseases has a broad spectrum of clinical and radiological presentations, from acute inflammatory to chronic, fibrosing predominance. For prognostic and therapeutic considerations a detailled work-up 'and optimally multidisciplinary evalution is needed, also to rule out other reasons for pulmonary deterioration such as infection (under immunosuppressive treatment) or pulmonary hypertension. For treatment guidance, several aspects need to be taken into consideration, such as disease severity, disease activity, clinical and radiological presentation, prognostic markers and comorbidities. Immunosuppressive treatment differs based on the type of rheumatologic diagnosis, although evidence for optimal therapy is rare in ILD associated with rheumatologic diseases. PMID- 26884220 TI - [Lung transplantation in patients with interstitial lung disease/idiopathic pulmonary fibrosis]. AB - Lung transplantation is an established therapy for advanced lung disease. Among the common disease indications for lung transplantation, patients with interstitial lung disease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation. PMID- 26884221 TI - Reasoning in psychosis: risky but not necessarily hasty. AB - INTRODUCTION: A liberal acceptance (LA) threshold for hypotheses has been put forward to explain the well-replicated "jumping to conclusions" (JTC) bias in psychosis, particularly in patients with paranoid symptoms. According to this account, schizophrenia patients rest their decisions on lower subjective probability estimates. The initial formulation of the LA account also predicts an absence of the JTC bias under high task ambiguity (i.e., if more than one response option surpasses the subjective acceptance threshold). METHODS: Schizophrenia patients (n = 62) with current or former delusions and healthy controls (n = 30) were compared on six scenarios of a variant of the beads task paradigm. Decision-making was assessed under low and high task ambiguity. Along with decision judgments (optional), participants were required to provide probability estimates for each option in order to determine decision thresholds (i.e., the probability the individual deems sufficient for a decision). RESULTS: In line with the LA account, schizophrenia patients showed a lowered decision threshold compared to controls (82% vs. 93%) which predicted both more errors and less draws to decisions. Group differences on thresholds were comparable across conditions. At the same time, patients did not show hasty decision-making, reflecting overall lowered probability estimates in patients. CONCLUSIONS: Results confirm core predictions derived from the LA account. Our results may (partly) explain why hasty decision-making is sometimes aggravated and sometimes abolished in psychosis. The proneness to make risky decisions may contribute to the pathogenesis of psychosis. A revised LA account is put forward. PMID- 26884222 TI - Bruxism in craniocervical dystonia: a prospective study. AB - AIMS: Bruxism pathophysiology remains unclear, and its occurrence has been poorly investigated in movement disorders. The aim of this study was to compare the frequency of bruxism in patients with craniocervical dystonia vs. normal controls and to determine its associated clinical features. METHOD: This is a prospective control study. A total of 114 dystonic subjects (45 facial dystonia, 69 cervical dystonia) and 182 controls were included. Bruxism was diagnosed using a hetero questionnaire and a clinical examination performed by trained dentists. Occurrence of bruxism was compared between the different study populations. A binomial logistic regression analysis was used to determine which clinical features influenced bruxism occurrence in each population. RESULTS: The frequency of bruxism was significantly higher in the dystonic group than in normal controls but there was no difference between facial and cervical dystonia. It was also higher in women than in men. Bruxism features were similar between normal controls and dystonic patients except for a higher score of temporomandibular jaw pain in the dystonic group. DISCUSSION: The higher frequency of bruxism in dystonic patients suggests that bruxism is increased in patients with basal ganglia dysfunction but that its nature does not differ from that seen in bruxers from the normal population. PMID- 26884223 TI - Running retraining to treat lower limb injuries: a mixed-methods study of current evidence synthesised with expert opinion. AB - IMPORTANCE: Running-related injuries are highly prevalent. OBJECTIVE: Synthesise published evidence with international expert opinion on the use of running retraining when treating lower limb injuries. DESIGN: Mixed methods. METHODS: A systematic review of clinical and biomechanical findings related to running retraining interventions were synthesised and combined with semistructured interviews with 16 international experts covering clinical reasoning related to the implementation of running retraining. RESULTS: Limited evidence supports the effectiveness of transition from rearfoot to forefoot or midfoot strike and increase step rate or altering proximal mechanics in individuals with anterior exertional lower leg pain; and visual and verbal feedback to reduce hip adduction in females with patellofemoral pain. Despite the paucity of clinical evidence, experts recommended running retraining for: iliotibial band syndrome; plantar fasciopathy (fasciitis); Achilles, patellar, proximal hamstring and gluteal tendinopathy; calf pain; and medial tibial stress syndrome. Tailoring approaches to each injury and individual was recommended to optimise outcomes. Substantial evidence exists for the immediate biomechanical effects of running retraining interventions (46 studies), including evaluation of step rate and strike pattern manipulation, strategies to alter proximal kinematics and cues to reduce impact loading variables. SUMMARY AND RELEVANCE: Our synthesis of published evidence related to clinical outcomes and biomechanical effects with expert opinion indicates running retraining warrants consideration in the treatment of lower limb injuries in clinical practice. PMID- 26884224 TI - Sports injuries and illnesses during the 2015 Winter European Youth Olympic Festival. AB - BACKGROUND: The prevention of injury and illness remains an important issue among young elite athletes. Systematic surveillance of injuries and illnesses during multi-sport events might provide a valuable basis to develop preventive measures, focusing especially on adequate information for youth athletes. AIM: To analyse the frequencies and characteristics of injuries and illnesses during the 2015 Winter European Youth Olympic Festival (W-EYOF). METHODS: All National Olympic Committees were asked to report daily the occurrence or non-occurrence of newly sustained injuries and illnesses on a standardised reporting form. RESULTS: Among the 899 registered athletes (37% female) with a mean age of 17.1+/-0.8 years, a total of 38 injuries and 34 illnesses during the 5 competition days of the W-EYOF were reported, resulting in an incidence of 42.3 injuries and 37.8 illnesses per 1000 athletes, respectively. Injury frequency was highest in snowboard cross (11%), Nordic combined (9%), alpine skiing (6%), and ice hockey (6%), taking into account the respective number of registered athletes. In snowboard cross, females showed a significant higher injury frequency compared to males (22% vs 4%, p=0.033). The lower back (16%), the pelvis (13%), the knee (11%), and the face (11%) were the most common injury locations. About 58% of injuries occurred in competition and about 42% in training. In total, 42% of injuries resulted in an absence of training or competition. The prevalence of illness was highest in figure skating (10%) and Nordic combined (9%), and the respiratory system was affected most often (53%). CONCLUSIONS: Four per cent of the athletes suffered from an injury and 4% from illnesses during the 2015 W-EYOF, which is about twofold lower compared to the first Winter Youth Olympic Games in 2012. PMID- 26884225 TI - Electro-thermal control of aluminum-doped zinc oxide/vanadium dioxide multilayered thin films for smart-device applications. AB - We demonstrate the electro-thermal control of aluminum-doped zinc oxide (Al:ZnO) /vanadium dioxide (VO2) multilayered thin films, where the application of a small electric field enables precise control of the applied heat to the VO2 thin film to induce its semiconductor-metal transition (SMT). The transparent conducting oxide nature of the top Al:ZnO film can be tuned to facilitate the fine control of the SMT of the VO2 thin film and its associated properties. In addition, the Al:ZnO film provides a capping layer to the VO2 thin film, which inhibits oxidation to a more energetically favorable and stable V2O5 phase. It also decreases the SMT of the VO2 thin film by approximately 5-10 degrees C because of an additional stress induced on the VO2 thin film and/or an alteration of the oxygen vacancy concentration in the VO2 thin film. These results have significant impacts on technological applications for both passive and active devices by exploiting this near-room-temperature SMT. PMID- 26884227 TI - The amygdalo-nigrostriatal network is critical for an optimal temporal performance. AB - The amygdalo-nigrostriatal (ANS) network plays an essential role in enhanced attention to significant events. Interval timing requires attention to temporal cues. We assessed rats having a disconnected ANS network, due to contralateral lesions of the medial central nucleus of the amygdala (CEm) and dopaminergic afferents to the lateral striatum, as compared to controls (sham and ipsilateral lesions of CEm and dopaminergic afferents to LS) in a temporal bisection task. ANS disconnection induced poorer temporal precision and increased response latencies to a short duration. The present results reveal a role of the ANS network in temporal processing. PMID- 26884226 TI - Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer. AB - PURPOSE: To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy. PATIENTS AND METHODS: A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose-volume histograms. RESULTS: SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively. CONCLUSION: High-dose and large volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose volume parameters without reducing the tumor dose. PMID- 26884229 TI - An appetitive conditioned stimulus enhances fear acquisition and impairs fear extinction. AB - Four experiments used between- and within-subject designs to examine appetitive aversive interactions in rats. Experiments 1 and 2 examined the effect of an excitatory appetitive conditioned stimulus (CS) on acquisition and extinction of conditioned fear. In Experiment 1, a CS shocked in a compound with an appetitive excitor (i.e., a stimulus previously paired with sucrose) underwent greater fear conditioning than a CS shocked in a compound with a neutral stimulus. Conversely, in Experiment 2, a CS extinguished in a compound with an appetitive excitor underwent less extinction than a CS extinguished in a compound with a neutral stimulus. Experiments 3 and 4 compared the amount of fear conditioning to an appetitive excitor and a familiar but neutral target CS when the compound of these stimuli was paired with shock. In each experiment, more fear accrued to the appetitive excitor than to the neutral CS. These results show that an appetitive excitor influences acquisition and extinction of conditioned fear to a neutral CS and itself undergoes a greater associative change than the neutral CS across compound conditioning. They are discussed with respect to the role of motivational information in regulating an associative change in appetitive aversive interactions. PMID- 26884228 TI - Chunking improves symbolic sequence processing and relies on working memory gating mechanisms. AB - Chunking, namely the grouping of sequence elements in clusters, is ubiquitous during sequence processing, but its impact on performance remains debated. Here, we found that participants who adopted a consistent chunking strategy during symbolic sequence learning showed a greater improvement of their performance and a larger decrease in cognitive workload over time. Stronger reliance on chunking was also associated with higher scores in a WM updating task, suggesting the contribution of WM gating mechanisms to sequence chunking. Altogether, these results indicate that chunking is a cost-saving strategy that enhances effectiveness of symbolic sequence learning. PMID- 26884230 TI - What-where-when memory and encoding strategies in healthy aging. AB - Older adults exhibit disproportionate impairments in memory for item associations. These impairments may stem from an inability to self-initiate deep encoding strategies. The present study investigates this using the "treasure-hunt task"; a what-where-when style episodic memory test that requires individuals to "hide" items around complex scenes. This task separately assesses memory for item, location, and temporal order, as well as bound what-where-when information. The results suggest that older adults are able to ameliorate integration memory deficits by using self-initiated encoding strategies when these are externally located and therefore place reduced demands on working memory and attentional resources. PMID- 26884232 TI - Endovascular embolectomy of the superior mesenteric artery using the Rotarex(r) system for the treatment of acute mesenteric ischemia. PMID- 26884231 TI - Effects of different dietary n-6/n-3 polyunsaturated fatty acid ratios on boar reproduction. AB - BACKGROUND: N-3 and N-6 polyunsaturated fatty acids are widely used in reproduction, yet few studies have addressed the effects of dietary n-6/n-3 ratios on boar reproduction. The present study aimed to determine the effects of different dietary n-6/n-3 ratios on the reproductive performance of breeding boars. Thirty-two boars with body weights of 15.0 +/- 1.4 kg were divided into four treatments (C, T1, T2, T3) and fed diets with different n-6/n-3 fatty acid ratios (29.06:1, 20.07:1, 1:1, 1:17.96, respectively) for 174 days. RESULTS: The highest testis index was observed for treatment T2. Sperm density and total sperm number per ejaculate in the T2 treatment were significantly higher than those in all other treatments, whereas the sperm deformity rate was the lowest. Interestingly, the fatty acid compositions and ratios of sperm were consistent with dietary treatments. Acid phosphatase and fructose concentration of seminal plasma, and the total superoxide dismutase and glutathione peroxidase of sperm in T2 were higher than those in other treatments. The concentration of testosterone and prostaglandin E2 increased in boars fed on diets supplemented with fatty acids as compared with boars subjected to the C group treatment, reaching a peak at n-6/n-3 fatty acid ratios of 1:1. Furthermore, higher expression of Delta(6) fatty acid desaturase and peroxisome proliferator activated receptor-alpha in spermatozoa of the T2 treatment were observed, indicating more vigorous metabolism and intensive hormonal regulation. CONCLUSIONS: Our data suggest that the ideal n-6/n-3 ratio in the diet of breeding boars is 1:1, and proper balancing of n-6/n-3 fatty acids plays an important role in male reproduction. PMID- 26884233 TI - Uterine fibroid characteristics and sonographic pattern among Ghanaian females undergoing pelvic ultrasound scan: a study at 3-major centres. AB - BACKGROUND: Uterine fibroids are the most common benign tumours affecting premenopausal women and are often associated with considerable hospitalization and morbidity. The purpose of this study was to identify the uterine fibroid characteristics and sonographic patterns of uterine fibroids among Ghanaian women undergoing abdomino-pelvic or pelvic ultrasound scan at three major diagnostic centres. The outcome is expected to help in appropriate policy formulation in women care in Ghana. METHOD: A total of two hundred and forty four (244) women were evaluated between November 2011-February 2012, using identical 2-5 MHz curvilinear probe of Philips HD3 ultrasound machines at three major diagnostic centers in Ghana, using a trans-abdominal pelvic approach. RESULTS: The range, mean and standard deviation (SD) of the patients' ages were 14-54 years, 31.89 years and +/- 7.92 respectively. The majority, 57.8% of the fibroids were intramural with only 4.4% noted as sub-mucosal. Most (55.6%) of the fibroids were located in more than one part of the uterus. The most popular (55.6%) echo pattern of the various fibroid nodules was mixed echogenicity. CONCLUSION: The sonographic patterns of uterine fibroids among Ghanaian women have been assessed at three major diagnostic centres. The study shows that most Ghanaian women who have fibroids have degenerative fibroid nodules as these nodules demonstrate mixed echo patterns on ultrasound. The findings may aid in appropriate diagnosis and interventions in the country. PMID- 26884234 TI - Prognostic value of the distance between the primary tumor and brainstem in the patients with locally advanced nasopharyngeal carcinoma. AB - BACKGROUND: Brainstem dose limitations influence radiation dose reaching to tumor in the patients with locally-advanced nasopharyngeal cancer (NPC). METHODS: A retrospective analysis of the prognostic value of the distance between the primary tumor and brainstem (Dbs) in 358 patients with locally-advanced NPC after intensity-modulated radiation therapy (IMRT). Receiver operating characteristic (ROC) curves were used to identify the cut-off value to analyze the impact of Dbs on tumor dose coverage and prognosis. RESULTS: The three-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were 88.8 vs. 78.4% (P = 0.007), 96.5 vs. 91.1% (P = 0.018), 87.8 vs. 79.3% (P = 0.067), and 84.1 vs. 69.6% (P = 0.002) for the patients with the Dbs > 4.7 vs. <= 4.7 mm, respectively. ROC curves revealed Dbs (4.7 mm) combined with American Joint Committee on Cancer (AJCC) T classification had a significantly better prognostic value for OS (P < 0.05). CONCLUSIONS: Dbs (<= 4.7 mm) is an independent negative prognostic factor for OS/LRFS/DFS and enhances the prognostic value of T classification in the patients with locally-advanced NPC. PMID- 26884236 TI - Erratum to: Serum concentrations of PCBs and OCPs among prepubertal Korean children. PMID- 26884235 TI - Diamondoid naphthenic acids cause in vivo genetic damage in gills and haemocytes of marine mussels. AB - Diamondoids are polycyclic saturated hydrocarbons that possess a cage-like carbon skeleton approaching that of diamond. These 'nano-diamonds' are used in a range of industries including nanotechnologies and biomedicine. Diamondoids were thought to be highly resistant to degradation, but their presumed degradation acid products have now been found in oil sands process-affected waters (OSPW) and numerous crude oils. Recently, a diamondoid-related structure, 3-noradamantane carboxylic acid, was reported to cause genetic damage in trout hepatocytes under in vitro conditions. This particular compound has never been reported in the environment but led us to hypothesise that other more environmentally relevant diamondoid acids could also be genotoxic. We carried out in vivo exposures (3 days, semi-static) of marine mussels to two environmentally relevant diamondoid acids, 1-adamantane carboxylic acid and 3,5-dimethyladamantane carboxylic acid plus 3-noradamantane carboxylic acid with genotoxic damage assessed using the Comet assay. An initial screening test confirmed that these acids displayed varying degrees of genotoxicity to haemocytes (increased DNA damage above that of controls) when exposed in vivo to a concentration of 30 MUmol L(-1). In a further test focused on 1-adamantane carboxylic acid with varying concentrations (0.6, 6 and 30 MUmol L(-1)), significant (P < 0.05%) DNA damage was observed in different target cells (viz. gills and haemocytes) at 0.6 MUmol L(-1). Such a level of induced genetic damage was similar to that observed following exposure to a known genotoxin, benzo(a)pyrene (exposure concentration, 0.8 MUmol L(-1)). These findings may have implications for a range of worldwide industries including oil extraction, nanotechnology and biomedicine. PMID- 26884237 TI - Effect of sugarcane vinasse and EDTA on cadmium phytoextraction by two saltbush plants. AB - Although the use of saltbush plants in metal phytoremediation is well known, there is little information about the impact of sugarcane vinasse (SCV) and EDTA on metal uptake. Heavily cadmium-polluted soil (38 mg kg(-1) Cd) was used in pot and incubation experiments to investigate the Cd phytoextraction potential of wavy saltbush (Atriplex undulata) and quail saltbush (Atriplex lentiformis). EDTA at rates of 3, 6, and 10 mM kg(-1) soil and SCV at rates of 7, 15, and 30 mL kg( 1) soil were added to the polluted soil. The application of EDTA significantly (P = 0.002) reduced the growth of saltbush plants; on the other hand, SCV improved the growth. Both EDTA and SCV increased the availability and root-to-shoot transfer of Cd. The plants of A. lentiformis grown on the soil amended with the highest rate of SCV were able to remove 20.4 % of the total soil Cd during a period of 9 months. Based on the obtained results, it may be concluded that A. lentiformis and sugarcane vinasse could be more effective in the phytoextraction of Cd from the polluted soils. PMID- 26884238 TI - Comparison of PARAFAC components of fluorescent dissolved and particular organic matter from two urbanized rivers. AB - Excitation-emission matrix (EEM) fluorescence spectroscopy combined with parallel factor analysis (PARAFAC) and multivariable analysis were employed to compare components of dissolved (DOM) and particulate (POM) organic matter and to reveal their correlations with water quality in Baitapuhe River and Xihe River in Shenyang City of northeast China. Eighteen water samples in Baitapuhe River and 16 water samples in Xihe River were collected along a human impact gradient. The DOM concentrations in Baitapuhe River were lower than those in Xihe River, so were the POM concentrations. The DOM in Baitapuhe River mainly derived from livestock wastewater and domestic sewage, which had strong biodegradability. However, the DOM in Xihe River mainly originated from industrial wastewater, which exhibited weak biodegradability. Four PARAFAC components (C1 to C4) were extracted from the DOM and POM. C1 was defined as fulvic-like component, and C2 was assigned as microbial humic component. C3 and C4 were ubiquitous protein-like component, which were referred as tryptophan-like and tyrosine-like components, respectively. The C3 was representative for the DOM in Baitapuhe River. The C3 and C4 were the main fractions of the DOM in Xihe River across the centralized wastewater-discharge region, whereas the C2 was the major component across the dispersed wastewater-discharge region. POM was dominated by the C4 in both rivers. Latent factors of water quality included the DOM, DO, Chl a, NO3-N, and NH4-N in Baitapuhe River, but the latent factors contained DOM, DO, BOD5, and COD in Xihe River. Baitapuhe River was under the aerobic condition, but Xihe River was under the anaerobic condition. PMID- 26884239 TI - Profiling the biological effects of wastewater samples via bioluminescent bacterial biosensors combined with estrogenic assays. AB - Various water samples were successfully evaluated using a panel of different recombinant bioluminescent bacteria and estrogenic activity analysis. The bioluminescent bacteria strains induced by oxidative (superoxide radical or hydroxyl radical), protein damage, cell membrane damage, or cellular toxicity were used. Estrogenic activities were examined by using the yeast strain BY4741, which carries the beta-galactosidase reporter gene under the control of the estrogen-responsive element (ERE). A total of 14 samples from three wastewater treatment plants, one textile factory, and seawater locations in Tunisia were analyzed. A wide range of bio-responses were described. Site/sample heterogeneity was prevalent, in combination with generally high relative bioluminescence scores for oxidative stress (OH*). Estrogenic activity was detected at all sites and was particularly elevated at certain sites. Our perspectives include the future exploration of the variation detected in relation to treatment plant operations and environmental impacts. In conclusion, this new multi-experimental method can be used for rapid bio-response profile monitoring and the evaluation of environmental samples spanning a wide range of domains. This study confirms that bio-reactive wastewater treatment plant (WWTP) effluents are discharged into seawater, where they may impact coastal populations. PMID- 26884240 TI - Exogenous IAA treatment enhances phytoremediation of soil contaminated with phenanthrene by promoting soil enzyme activity and increasing microbial biomass. AB - In this study, we aimed to confirm that indole-3-acetic acid promotes plant uptake of phenanthrene (PHE), stimulates the activity of soil enzymes or microflora, and thereby accelerates the dissipation of PHE in soil. Four treatments were evaluated: PHE-contaminated soil planted with (1) ryegrass (T0), (2) ryegrass and supplemented with 1 mg kg(-1) indole-3-acetic acid (IAA) (T1), (3) ryegrass and supplemented with 5 mg kg(-1) IAA (T5), and (4) ryegrass and supplemented with 10 mg kg(-1) IAA (T10). After 30 days, PHE concentrations were lower for all treatments and the removal rate was 70.19, 89.17, 91.26, and 97.07 % for T0, T1, T5, and T10, respectively. PHE was only detected in the roots and not in the shoots. IAA facilitated the accumulation of PHE in the roots, and plants subjected to the T10 treatment had the highest levels. Exogenous IAA stimulated soil peroxidase activity in a dose-dependent manner, whereas soil polyphenoloxidase activity was not significantly increased, except in T10. Soil microbial biomass also increased in response to IAA treatment, particularly in T10. Furthermore, phospholipid fatty acid analysis showed that IAA treatment increased microbial biomass and alleviated environmental stress. Gram-positive bacteria are largely responsible for polycyclic aromatic hydrocarbon degradation, and we found that the ratio of gram-positive to gram-negative bacteria in the soil significantly increased as the IAA concentrations increased (P < 0.05). Correlation analysis indicated that the increase in soil microbial biomass, enzyme activity, and plant uptake of PHE promotes removal of PHE from the soil. PMID- 26884241 TI - Are participants in markets for water rights more efficient in the use of water than non-participants? A case study for Limari Valley (Chile). AB - The need to increase water productivity in agriculture has been stressed as one of the most important factors to achieve greater agricultural productivity and sustainability. The main aim of this paper is to investigate whether there are differences in water use efficiency (WUE) between farmers who participate in water markets and farmers who do not participate in them. Moreover, the use of a non-radial data envelopment analysis model allows to compute global efficiency (GE), WUE as well the efficiency in the use of other inputs such as fertilizers, pesticides, energy, and labor. In a second stage, external factors that may affect GE and WUE are explored. The empirical application focuses on a sample of farmers located in Limari Valley (Chile) where regulated permanent water rights (WR) markets for surface water have a long tradition. Results illustrate that WR sellers are the most efficient in the use of water while non-traders are the farmers that present the lowest WUE. From a policy perspective, significant conclusions are drawn from the assessment of agricultural water productivity in the framework of water markets. PMID- 26884242 TI - On the bioavailability of trace metals in surface sediments: a combined geochemical and biological approach. AB - The bioavailability of metals was estimated in three river sediments (Sensee, Scarpe, and Deule Rivers) impacted by different levels of Cu, Cd, Pb, and Zn (Northern France). For that, a combination of geochemistry and biological responses (bacteria and chironomids) was used. The results obtained illustrate the complexity of the notion of "bioavailability." Indeed, geochemical indexes suggested a low toxicity, even in surface sediments with high concentrations of total metals and a predicted severe effect levels for the organisms. This was also suggested by the abundance of total bacteria as determined by DAPI counts, with high bacterial cell numbers even in contaminated areas. However, a fraction of metals may be bioavailable as it was shown for chironomid larvae which were able to accumulate an important quantity of metals in surface sediments within just a few days.We concluded that (1) the best approach to estimate bioavailability in the selected sediments is a combination of geochemical and biological approaches and that (2) the sediments in the Deule and Scarpe Rivers are highly contaminated and may impact bacterial populations but also benthic invertebrates. PMID- 26884243 TI - Phytoextraction of Cd and Zn as single or mixed pollutants from soil by rape (Brassica napus). AB - This paper analyses the capacity of the rape (Brassica napus) to extract Cd and Zn from the soil and the effect of these metals on the morphometric parameters of the plant (length, weight, surface area, fractal dimension of leaves). Rape plants were mostly affected by the combined toxicity of the Cd and Zn mixture that caused a significant reduction in the rate of seed germination, the plant biomass quantity and the fractal dimension. In the case of Cd soil pollution, the bioaccumulation factor (BAF), bioaccumulation coefficient (BAC) as well as the heavy metal root-to-stalk translocation factor (TF) were determined. The results showed that B. napus had a great potential as a cadmium hyperaccumulator but not as an accumulator of Zn or Cd + Zn mixture. The efficiency of phytoextraction rape was 0.8-1.22 % for a soil heavily polluted with cadmium. PMID- 26884245 TI - Mustard plant ash: a source of micronutrient and an adsorbent for removal of 2,4 dichlorophenoxyacetic acid. AB - The work highlights the utilization of an agricultural waste mustard plant ash (MPA) as a soil additive and an adsorbent. MPA was characterized by X-ray fluorescence (XRF), energy-dispersive X-ray spectroscopy (EDX), proximate analysis, CHNS analysis, Brunauer-Emmett-Teller (BET) surface area analysis, zeta potential measurements, Fourier transform infrared (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). XRF analysis confirmed the presence of CaO (31.35 %), K2O (18.55 %), and P2O5 (6.99 %), all of which act as micronutrients to plants. EDX also confirms high amount of elemental O, Ca, K, and P. The adsorptive ability of MPA was investigated using a commonly used herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), as a representative chemical. Batch adsorption experiments were conducted to study the effect of different operational parameters such as adsorbent dose, initial 2,4-D concentration, contact time, and temperature on the adsorption process. Data from experiments were fitted to various kinetic and isothermal models. The pseudo second-order kinetic model was found to show the best fit (R 2 > 0.99), with the highest k 2 value of the order 105. Based on the study results, dosage of MPA/hectare for different crops has been recommended for effective removal of 2,4 D. To our knowledge, this is the first study in which MPA has been characterized in detail and investigated for dual applications (as an adsorbent and as a soil additive). PMID- 26884244 TI - Airborne polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p dioxins/furans (PBDD/Fs), and dechlorane plus (DP) in concentrated vehicle parking areas. AB - This study investigated polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and dechlorane plus (DP) in air around three concentrated vehicle parking areas (underground, indoor, and outdoor) in a metropolitan of South China. The parking areas showed higher concentrations of PBDEs, PBDD/Fs, and DP than their adjacent urban area or distinct congener/isomer profiles, which indicate their local emission sources. The highest PBDE and DP concentrations were found in the outdoor parking lot, which might be related to the heating effect of direct sunlight exposure. Multi-linear regression analysis results suggest that deca-BDEs without noticeable transformation contributed most to airborne PBDEs in all studied areas, followed by penta-BDEs. The statistically lower anti-DP fractions in the urban area than that of commercial product signified its degradation/transformation during transportation. Neither PBDEs nor vehicle exhaust contributed much to airborne PBDD/Fs in the parking areas. There were 68.1-100 % of PBDEs, PBDD/Fs, and DP associated with particles. Logarithms of gas-particle distribution coefficients (K ps) of PBDEs were significantly linear-correlated with those of their sub-cooled vapor pressures (p Ls) and octanol-air partition coefficients (K OAs) in all studied areas. The daily inhalation doses of PBDEs, DP, and PBDD/Fs were individually estimated as 89.7 10,741, 2.05-39.4, and 0.12-4.17 pg kg(-1) day(-1) for employees in the parking areas via Monte Carlo simulation. PMID- 26884247 TI - Incidence, location and classification of glenoid labrum meniscoid folds. AB - INTRODUCTION: The purpose of the present study was to arthroscopically investigate the incidence and location of labral meniscoid folds of the shoulder joint, as well as to classify them into types and detect any possible correlation with gender, side and age of patients. MATERIALS AND METHODS: The shoulder joint of 59 patients who underwent arthroscopic surgery for different reasons was examined for meniscoid folds. We classified all meniscoid folds into slim or thick and large or small. The location and area of labral folds were assessed according to o'clock position and were defined by the center of the fold. RESULTS: The incidence of labral meniscoid folds in shoulder joint was 62.7 %. Meniscoid folds were more frequently found at 2-o'clock position in right shoulders and at 10-o'clock position in left shoulders. Most of them were located in anterior and superior rim of labrum. Statistically significant difference (p = 0.018) was only detected between location of meniscoid folds and gender. In male patients meniscoid folds were mostly located in a more anterior position than women, whose meniscoid folds were found more superiorly. Older patients presented a higher rate of meniscoid folds. CONCLUSION: Meniscoid folds are quite common in shoulder joint. Labral meniscoid folds are located more often at an anterosuperior position of shoulder joints and their incidence tends to be higher in older patients, while in male ones they are located in a more anterior position in comparison to female patients where they are located more superiorly. PMID- 26884248 TI - Controlled synthesis and photocatalysis of sea urchin-like Fe3O4@TiO2@Ag nanocomposites. AB - Based on the synergistic photocatalytic activities of nano-sized TiO2 and Ag, as well as the magnetic properties of Fe3O4, a sea urchin-like Fe3O4@TiO2@Ag nanocomposite (Fe3O4@TiO2@Ag NCs) is controllably synthesized with tunable cavity size, adjustable shell layer of TiO2 nanofiber, higher structural stability and larger specific surface area. Here, Fe3O4@TiO2@Ag NCs are obtained with Fe3O4 as the core and nanofiber TiO2/Fe3O4/Ag nanoheterojunctions as the shell; and Ag nanoparticles with diameter of approximately 4 nm are loaded both on TiO2 nanofibers and inside the cavities of sea urchin-like Fe3O4@TiO2 nanocomposites uniformly. Ag nanoparticles lead to the production of more photogenerated charges in the TiO2/Fe3O4/Ag heterojunction via LSPR absorption, and enhance the band-gap absorption of TiO2, while the Fe3O4 cocatalyst provides the active sites for oxygen reduction by the effective transfer of photogenerated electrons to oxygen. So the photocatalytic performance is improved due to the synergistic effect of TiO2/Fe3O4/Ag nanoheterojunctions. As photocatalysts under UV and visible irradiation, the as-synthesized nanocomposites display enhanced photocatalytic and recycling properties for the degradation of ampicillin. Moreover, they present better broad-spectrum antibiosis under visible irradiation. The enhanced photocatalytic activity and excellent chemical stability, in combination with the magnetic recyclability, makes this multifunctional nanostructure a promising candidate for antibiosis and remediation in aquatic environmental contamination in the future. PMID- 26884246 TI - Reclassification of genetic-based risk predictions as GWAS data accumulate. AB - BACKGROUND: Disease risk assessments based on common genetic variation have gained widespread attention and use in recent years. The clinical utility of genetic risk profiles depends on the number and effect size of identified loci, and how stable the predicted risks are as additional loci are discovered. Changes in risk classification for individuals over time would undermine the validity of common genetic variation for risk prediction. In this analysis, we quantified reclassification of genetic risk based on past and anticipated future GWAS data. METHODS: We identified disease-associated SNPs via the NHGRI GWAS catalog and recent large scale genome-wide association study (GWAS). We calculated the genomic risk for a simulated cohort of 100,000 individuals based on a multiplicative odds ratio model using cumulative GWAS-identified SNPs at four time points: 2007, 2009, 2011, and 2013. Individuals were classified as Higher Risk (population adjusted odds >2), Average Risk (between 0.5 and 2), and Lower Risk (<0.5) for each time point and we compared classifications between time points for breast cancer (BrCa), prostate cancer (PrCa), diabetes mellitus type 2 (T2D), and cardiovascular heart disease (CHD). We estimated future reclassification using the anticipated number of undiscovered SNPs. RESULTS: Risk reclassification occurred for all four phenotypes from 2007 to 2013. During the most recent interval (2011-2013), the degree of risk reclassification ranged from 16.3 % for CHD to 24.4 % for PrCa. Many individuals classified as Higher Risk at earlier time points were subsequently reclassified into a lower risk category. From 2011 to 2013, the degree of such downward risk reclassification ranged from 24.9% for T2D to 55% for CHD. The percent of individuals classified as Higher Risk increased as more SNPs were discovered, ranging from an increase of 5% for CHD to 9% for PrCa from 2007 to 2013. Reclassification continued to occur when we modeled the discovery of anticipated SNPs based on doubling current sample size. CONCLUSION: Risk estimates from common genetic variation show large reclassification rates. Identifying disease-associated SNPs facilitates the clinically relevant task of identifying higher-risk individuals. However, the large amount of reclassification that we demonstrated in individuals initially classified as Higher Risk but later as Average Risk or Lower Risk, suggests that caution is currently warranted in basing clinical decisions on common genetic variation for many complex diseases. PMID- 26884249 TI - Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells. AB - Anaplastic thyroid carcinoma (ATC) is an extremely aggressive human malignancy characterized by a marked degree of invasiveness, absense of features of thyroid differentiation and resistance to current medical treatment. It is well known that ATCs are characterized by deregulation of genes related to cell cycle regulation, i.e., cyclin-dependent kinases (CDKs) and endogenous cyclin-dependent kinase inhibitors (CDKIs). Therefore, in the present study, the effect of a novel exogenous cyclin-dependent kinase inhibitor, BP-14, was investigated in three human ATC cell lines. The ATC-derived cell lines FRO, SW1736 and 8505C were treated with BP-14 alone or in combination with the mTOR inhibitor everolimus. In all ATC cell lines, treatment with BP-14 decreased cell viability and, in two of them, BP-14 modified expression of genes involved in epithelial-mesenchymal transition. Thus, our data indicate that BP-14 is a potential new compound effective against ATC. Combined treatment with BP-14 and the mTOR inhibitor everolimus had a strong synergistic effect on cell viability in all three cell lines, suggesting that the combined used of CDK and mTOR inhibitors may be a useful strategy for ATC treatment. PMID- 26884251 TI - Ulinastatin administration is associated with a lower incidence of acute kidney injury after cardiac surgery: a propensity score matched study. AB - BACKGROUND: Systemic inflammation is involved in the development of acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Ulinastatin, a urinary trypsin inhibitor (UTI), possesses a variety of anti inflammatory effects. Therefore, we hypothesized that the administration of ulinastatin would reduce the occurrence of AKI in patients undergoing cardiac surgery with CPB. METHODS: A retrospective propensity score matched analysis was used to evaluate the effect of ulinastatin on the development of AKI in patients undergoing first documented cardiac surgery with CPB between January 2008 and December 2012 in our hospital. Multiple logistic regression models were also employed to identify the association between UTI administration and development of AKI. RESULTS: A total of 2072 patients who underwent cardiac surgery with CPB met the inclusion criteria. Before propensity score matching, variables such as age, baseline creatinine, CPB duration, red blood cells transfused, and hematocrit were statistically different between the ulinastatin (UTI) group and the control group. On the basis of propensity scores, 409 UTI patients were successfully matched to the 409 patients from among those 1663 patients without UTI administration. After propensity score matching, no statistically significant differences in the baseline characteristics were found between the UTI group and the control group. The propensity score matched cohort analysis revealed that AKI and the need for renal replacement therapy occurred more frequently in the control group than in the UTI group (40.83% vs. 30.32%, P = 0.002; 2.44% vs. 0.49%, P = 0.02, respectively). However, there were no significant differences in mortality, length of intensive care unit stay, and length of hospital stay between the UTI group and the control group. Using multivariate logistic regression analysis, we found ulinastatin played a protective role in the development of AKI after cardiac surgery (odds ratio 0.71, 95% confidence interval 0.56-0.90, P = 0.005). CONCLUSIONS: This study shows that ulinastatin was associated with a lower incidence of AKI after cardiac surgery, suggesting that the administration of ulinastatin may be favorable for those patients undergoing cardiac surgery with CPB. PMID- 26884252 TI - Traumatic dental injury. AB - BACKGROUND: The aim of this study was to retrospectively evaluate the incidence of traumatic dental injury and consequential dental impairment following road traffic accidents and to examine the factors that can affect the monetary value of compensation for bodily injury payable pursuant to current insurance regulations. METHODS: From 2004 to 2014, 7233 persons involved in road traffic accidents in the province of Messina, eastern Sicily, were examined by insurance physicians to assess bodily injury damage. Data were collected from cases of traumatic dental injury causing malocclusion and temporomandibular joint dysfunction, either alone or concomitant with injuries to other parts of the body. Injury characteristics and consequential bodily injury damage were classified and the incidence calculated using Microsoft Excel software. RESULTS: The incidence of traumatic dental injuries was 3% of the total population (195 subjects - 127 males and 68 females); the majority of cases (56%) involved riders of two-wheeled vehicles. A high percentage of riders received injury to one or more teeth, i.e. fractures and dislocations, more frequently to the anterior teeth (68%) than the posterior teeth because of their position in the dental arch. Temporomandibular joint injuries were far fewer (8%) and resulted from either direct or indirect trauma associated with severe head and/or neck injury. The incidence of permanent bodily damage consequential to these injuries was fairly low. CONCLUSIONS: Although the incidence of dental trauma following road traffic accidents is low, the monetary compensation for consequential dental impairment based on current insurance regulatory law is far from negligible. PMID- 26884254 TI - Patterns of healing: a comparison of two proximal tibial osteotomy techniques. AB - Several low-energy osteotomy techniques are described in the literature, but there is limited evidence comparing them. Our study evaluates the patterns of regenerate formation using two different osteotomy techniques. Two cohorts of patients underwent osteotomy of the tibia using a Gigli saw (n = 15) or De Bastiani corticotomy (n = 12) technique. The patient radiographs were assessed by the two senior authors who were blinded to the osteotomy type. Regenerate quality was assessed along the anterior, posterior, medial and lateral cortices, graded 1 5 from absent to full consolidation over time. The time to 3 cortices healed/regenerate length was calculated. The time to consolidation of the anterior, posterior, medial and lateral cortices was compared. The mean 3 cortices index in the Gigli group was 2.0 months/cm and in the De Bastiani group 1.8 months/cm. This was not a significant difference. In both groups, anterior bone formation was slower, and anterior cortical deficiency with a scalloped appearance was seen in 25 % of cases overall with no statistically significant difference between the two groups. Both Gigli saw and De Bastiani corticotomy techniques result in good bone formation following distraction osteogenesis. The anterior tibial cortex consolidates more slowly than the other cortices in both groups. This is likely due to deficient soft tissue cover and direct periosteal damage at time of osteotomy. PMID- 26884253 TI - Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells. AB - The spatial boundary condition (SBC) arising from the surrounding microenvironment imposes specific geometry and spatial constraints that affect organogenesis and tissue homeostasis. Mesenchymal stromal cells (MSCs) sensitively respond to alterations of mechanical cues generated from the SBC. However, mechanical cues provided by a three-dimensional (3D) environment are deprived in a reductionist 2D culture system. This study investigates how SBC affects osteogenic differentiation of MSCs using 3D scaffolds with monodispersed pores and homogenous spherical geometries. MSCs cultured under SBCs with diameters of 100 and 150 MUm possessed the greatest capability of osteogenic differentiation. This phenomenon was strongly correlated with MSC morphology, organization of actin cytoskeleton, and distribution of focal adhesion involving alpha2 and alpha5 integrins. Further silencing either alpha2 or alpha5 integrin significantly reduced the above mentioned mechanosensitivity, indicating that the alpha2 and alpha5 integrins as mechano-sensitive molecules mediate MSCs' ability to provide enhanced osteogenic differentiation in response to different spherical SBCs. Taken together, the findings provide new insights regarding how MSCs respond to mechanical cues from the surrounding microenvironment in a spherical SBC, and such biophysical stimuli should be taken into consideration in tissue engineering and regenerative medicine in conjunction with biochemical cues. PMID- 26884255 TI - Infravalvular type of Gerbode defect: a rare cardiac anomaly. PMID- 26884256 TI - Connexin 43, breast cancer tumor suppressor: Missed connections? AB - Connexins are a family of transmembrane proteins that are characterized by their capacity to form intercellular channels called gap junctions that directly link the cytoplasm of adjacent cells. The formation of gap junctions by connexin proteins facilitates intercellular communication between neighboring cells by allowing for the transfer of ions and small signaling molecules. Communication through gap junctions is key to cellular equilibrium, where connexins, and the gap junction intercellular communication that connexins propagate, have roles in cellular processes such as cell growth, differentiation, and tissue homeostasis. Due to their importance in maintaining cellular functions, the disruption of connexin expression and function underlies the etiology and progression of numerous pathologies, including cancer. Over the past half a century, the role of connexins and gap junction intercellular communication have been highlighted as critical areas of research in cellular malignancies, and much research effort has been geared toward understanding their dysfunction in human cancers. Although ample evidence supports the role of connexins in a variety of human cancers, detailed examination in specific cancers, such as breast cancer, is still lacking. This review highlights the most abundant gap junction connexin isoform in higher vertebrate organisms, Connexin 43, and its role in breast cancer. PMID- 26884257 TI - 17beta-Hydroxysteroid dehydrogenase type 10 predicts survival of patients with colorectal cancer and affects mitochondrial DNA content. AB - Mitochondrial energy production is reduced in tumor cells, and altered mitochondrial respiration contributes to tumor progression. Synthesis of proteins coded by mitochondrial DNA (mtDNA) requires the correct processing of long polycistronic precursor RNA molecules. Mitochondrial RNase P, composed of three different proteins (MRPP1, HSD10, and MRPP3), is necessary for correct RNA processing. Here we analyzed the role of RNase P proteins in colorectal cancer. High HSD10 expression was found in 28%; high MRPP1 expression in 40% of colorectal cancers, respectively. Expression of both proteins was not significantly associated with clinicopathological parameters. Survival analysis revealed that loss of HSD10 expression is associated with poor prognosis. Cox regression demonstrated that patients with high HSD10 tumors are at lower risk. High HSD10 expression was significantly associated with high mtDNA content in tumor tissue. A causal effect of HSD10 overexpression or knock down with increased or reduced mtDNA levels, respectively, was confirmed in tumor cell lines. Our data suggest that HSD10 plays a role in alterations of energy metabolism by regulating mtDNA content in colorectal carcinomas, and HSD10 protein analysis may be of prognostic value. PMID- 26884259 TI - Robustness is the kind of coherence that matters: a comment on Kendler (2015)--a reply. PMID- 26884258 TI - Transcriptional induction of protein kinase C delta by p53 tumor suppressor in the apoptotic response to DNA damage. AB - Genetic alterations and aberrant gene expression trigger malignant tumors. Tumor suppressor p53 is the most altered gene in human cancers. p53 induces apoptosis by promoting pro-apoptotic genes in response to DNA damage. Protein kinase C delta (PKCdelta) also induces apoptosis via various mechanisms including modification of p53. The PKCdelta-dependent apoptotic mechanism has been extensively studied; however, the transcriptional regulation of PKCdelta remains obscure. The current study demonstrates the transcriptional regulation of PKCdelta by p53 upon genotoxic stress. The p53-binding site in the promoter region of PKCdelta was detected by the ChIP-sequencing assay. Notably, the expression of PKCdelta was increased upon DNA damage, which is required for the stabilization of p53. More importantly, targeting single guide RNA-driven dead Cas9 to the p53-binding site of PKCdelta disturbed p53-promoted PKCdelta expression and suppressed apoptosis following DNA damage. Thus, our findings suggest that the transcriptional regulation of PKCdelta is controlled by p53 in a positive feedback mechanism to induce apoptosis in response to DNA damage. PMID- 26884260 TI - One-pot modification of 5'-capped RNA based on methionine analogs. AB - This paper outlines chemically and enzymatically synthesized S-adenosylmethionine (AdoMet) analogs and their use in the site-specific modification of RNA by methyltransferases, enabling the facile attachment of clickable moieties to the nucleic acid. We then focus on methodological aspects of setting up a methyltransferase-based enzymatic cascade reaction starting from methionine analogs. This strategy is applied to the one-pot modification of the mRNA cap which is subsequently derivatized in copper-free and copper-catalyzed click reactions. We show that high transfer efficiencies to the cap are obtained using Se-propargyl-, hexenynyl- and azido-bearing methionine analogs. By switching to other methyltransferases our one-pot modification approach should be directly applicable to the regiospecific modification of other target molecules including nucleic acids, proteins and small molecules. PMID- 26884262 TI - Inherent Strength of the osteo-WEDGE(TM) Bone Plate Locking System for Arthrodesis of the First Metatarsocuneiform Joint: A Biomechanical Study. AB - First metatarsocuneiform joint arthrodesis with a locking bone plate and screw system has been effectively used to correct metatarsus primus varus and instability of the first ray. The goal of the present cadaveric biomechanical study was to quantify and compare the inherent strength of the first metatarsocuneiform joint and surrounding bones fixated with the osteo-WEDGE(TM) bone plate locking system (OW) with that of intact specimens. Fourteen fresh frozen adult human cadaveric foot specimens consisting of the first metatarsal and medial cuneiform bones with intact joint capsules and ligaments were used. The OW was implanted in 7 of these specimens at the first metatarsal cuneiform joint (MCJ), and the remaining 7 specimens were left intact. Each of the specimens was then subjected to axial force to simulate dorsiflexion of the first metatarsal using a cantilever bending test setup. Load was applied on the plantar aspect of the first metatarsal head until failure of the construct. The mean load and bending moment on the first MCJ at failure for the implanted specimens were 119.98 +/- 56.76 N and 5.57 +/- 2.71 Nm, respectively. For the intact specimens, the mean load and bending moment on the first MCJ at failure were 107.93 +/- 60.90 N and 6.07 +/- 3.18 Nm, respectively. None of the specimens showed catastrophic failure within the physiologic loading limits. These results imply that the mechanical strength of the OW is comparable to that of intact specimens. Thus, the first MCJ and surrounding bones fixated with an OW should be able to effectively withstand the vertical ground reaction forces the same as intact specimens. PMID- 26884263 TI - Anterior Approach Total Ankle Arthroplasty: Superficial Peroneal Nerve Branches at Risk. AB - In ankle arthroplasty, little attention has been given to intraoperative nerve injury and its postoperative sequelae. The aim of the present anatomic study was to determine the relationship of the superficial peroneal nerve to the standard anterior approach for total ankle arthroplasty. The superficial peroneal nerve was dissected in 10 below-the-knee cadaver specimens. The medial and intermediate dorsal cutaneous branches were identified. A needle was placed at the ankle joint. The following measurements were recorded: bifurcation into the medial and intermediate dorsal cutaneous branches, reference needle to the branches of the medial and intermediate superficial peroneal nerve, and the crossing branches of the medial dorsal cutaneous nerve. Two specimens (20%) had a medial dorsal cutaneous branch cross from medially to laterally. Eight specimens (80%) had a crossing branch of the medial dorsal cutaneous branch within 5 cm of the incision. No intermediate dorsal cutaneous branches were within the incision. The results from the present cadaver study suggest that during an anterior ankle approach, aberrant branches of the superficial peroneal nerve could require transection in 20% of patients at the joint level and <=80% of patients with distal extension >35 mm from the ankle joint. The risk of injury to branches of the superficial peroneal nerve is substantial. The risk of nerve injury can be decreased with meticulous operative technique, smaller incisions, and the avoidance of aggressive retraction. PMID- 26884261 TI - Continuous changes in structure mapped by manifold embedding of single-particle data in cryo-EM. AB - Cryo-electron microscopy, when combined with single-particle reconstruction, is a powerful method for studying macromolecular structure. Recent developments in detector technology have pushed the resolution into a range comparable to that of X-ray crystallography. However, cryo-EM is able to separate and thus recover the structure of each of several discrete structures present in the sample. For the more general case involving continuous structural changes, a novel technique employing manifold embedding has been recently demonstrated. Potentially, the entire work-cycle of a molecular machine may be observed as it passes through a continuum of states, and its free-energy landscape may be mapped out. This technique will be outlined and discussed in the context of its application to a large single-particle dataset of yeast ribosomes. PMID- 26884264 TI - Salvage of Failed Total Ankle Replacement Using a Custom Titanium Truss. AB - Subsidence of the talar component results in significant morbidity after total ankle replacement. When recognized, prompt revision could be needed to preserve the function of the implant; however, this is not always the case. In situations in which the implant cannot be revised, tibiotalocalcaneal arthrodesis might be necessary to salvage the extremity. The purpose of the present report is to describe the use of a custom titanium alloy truss to fill a bony void created by explantation of the implant components. Total ankle replacement was performed as the initial surgery to address end-stage osteoarthritis. Two years after the index procedure, the patient underwent revision of the polyethylene and talar components with subtalar arthrodesis secondary to progressive subtalar osteoarthritis and talar subsidence. The implant subsequently became infected and was removed. The patient underwent re-implantation after the infection had resolved, but significant talar subsidence required conversion to a tibiotalocalcaneal arthrodesis with a custom titanium alloy truss and retrograde intramedullary nail. At the most recent follow-up appointment, the patient was weightbearing on a stable extremity and pain free. Radiographic examination confirmed appropriate implant alignment and evidence of bone formation throughout the titanium truss. Although our results are restricted to a single case with initial, limited follow-up data, combining sound structural mechanics with an open architecture and unique texture, the custom titanium truss appears to maintain the limb length and promote healing across a large void. PMID- 26884265 TI - CD105 Over-expression Is Associated with Higher WHO Grades for Gliomas. AB - CD105 is an ancillary receptor of transforming growth factor beta (TGF-beta), which has been suggested as a suitable biomarker for cancer-related angiogenesis and neovascularization (Nassiri et al. in Anticancer Res 31:2283-2290, 2011). However, the clinical significance of CD105 in WHO grade was rarely reported and the effects of CD105 signal transduction pathway on gliomas remain controversial and unclear. To get a convincing conclusion, performing a meta-analysis is essential. Relevant literature studies were included via careful evaluation, and standard mean difference (SMD) and hazard ratio (HR) with 95 % confidence intervals (95 % CIs) was calculated. We also made funnel plots to test the heterogeneity. In the present meta-analysis, a total of 11 eligible literatures involving 796 patients were incorporated. They were all conducted in China, revealing that CD105 overexpression in glioma tissues was strongly linked to high WHO grading (III+IV) (SMD -1.785, 95 % CI -2.133, -1.437; p = 0.000). No significant associations between CD105 and age (SMD -0.505, 95 % CI -1.054, 0.043; p = 0. 071), CD105 and gender (SMD 0.101, 95 % CI -0.103, 0.305; p = 0.333), and CD105 and tumor size (SMD -0.433, 95 % CI -1.326, 0.459; p = 0. 341) were detected. Besides, CD105 expression was closely associated with glioma patients' 3-year overall survival (OS; n = 2; HR = 4.357, 95 % CI 1.412, 7.303; p = 0.004). On the basis of Begg's and Egger's test or funnel plot, no publication bias was detected. In a nutshell, this meta-analysis demonstrated that CD105 overexpression correlates to higher WHO grade and poor survival and could be indicated as a helpful prognostic and diagnostic marker, or a useful therapy target. PMID- 26884266 TI - Transduction Profile of the Marmoset Central Nervous System Using Adeno Associated Virus Serotype 9 Vectors. AB - The common marmoset is a small New World primate that has attracted remarkable attention as a potential experimental animal link between rodents and humans. Adeno-associated virus (AAV) vector-mediated expression of a disease-causing gene or a potential therapeutic gene in the brain may allow the construction of a marmoset model of a brain disorder or an exploration of the possibility of gene therapy. To gain more insights into AAV vector-mediated transduction profiles in the marmoset central nervous system (CNS), we delivered AAV serotype 9 (AAV9) vectors expressing GFP to the cisterna magna or the cerebellar cortex. Intracisternally injected AAV9 vectors expanded in the CNS according to the cerebrospinal fluid (CSF) flow, by retrograde transport through neuronal axons or via intermediary transcytosis, resulting in diffuse and global transduction within the CNS. In contrast, cerebellar parenchymal injection intensely transduced a more limited area, including the cerebellar cortex and cerebellar afferents, such as neurons of the pontine nuclei, vestibular nucleus and inferior olivary nucleus. In the spinal cord, both administration routes resulted in labeling of the dorsal column and spinocerebellar tracts, presumably by retrograde transport from the medulla oblongata and cerebellum, respectively. Motor neurons and dorsal root ganglia were also transduced, possibly by diffusion of the vector down the subarachnoid space along the cord. Thus, these two administration routes led to distinct transduction patterns in the marmoset CNS, which could be utilized to generate different disease animal models and to deliver therapeutic genes for the treatment of diseases affecting distinct brain areas. PMID- 26884268 TI - Red vs. green: Does the exam booklet color matter in higher education summative evaluations? Not likely. AB - We examined the so-called "red effect" in the context of higher education summative exams under the premise that unlike the conditions or situations where this effect typically has been obtained, the totality of factors, such as higher motivation, familiarity with exam material, and more reliance on domain knowledge that characterize high-stakes testing such as those in operational educational settings, are likely to mitigate any color effects. Using three naturally occurring archival data sets in which students took exams on either red or green exam booklets, the results indicated that booklet color (red vs. green) did not affect exam performance. From a scientific perspective, the results suggest that color effects may be attenuated by factors that characterize high-stakes assessments, and from an applied perspective, they suggest that the choice of red vs. green exam booklets in higher education summative evaluations is likely not a concern. PMID- 26884269 TI - Analysis of the (1)A' S1 <- (1)A' S0 and (2)A' D0 <- (1)A' S1 band systems in 1,2 dichloro-4-fluorobenzene by means of resonance-enhanced-multi-photon-ionization (REMPI) and mass-analyzed-threshold-ionization (MATI) spectroscopy. AB - Resonance enhanced multiphoton ionization (REMPI) and mass analyzed threshold ionization (MATI) spectroscopy have been applied in order to investigate the vibrational structure of 1,2-dichloro-4-fluorobenzene (1,2,4-DCFB) in its first excited state (S1) and the cationic ground state (D0). The selection of the state prior to ionization resulted in MATI spectra with different intensity distributions thus giving access to many vibrational levels. To support the experimental findings, geometry optimizations and frequency analyses at DFT (density functional) and TDDFT (time-dependent density functional) levels of theory have been applied. Additionally, a multidimensional Franck-Condon approach has been used to calculate the vibrational intensities from the DFT calculations. An excellent agreement between simulated and measured REMPI and MATI spectra allowed for a confident assignment of vibrational levels and mechanisms active during excitation and ionization. In order to avoid any ambiguity regarding the assignment of the vibrational bands to normal modes, Duschinsky normal mode analysis has been performed to correlate the ground state (S0) normal modes of 1,2,4-DCFB with the benzene derived Wilson nomenclature. From the REMPI spectra the electronic excitation energy (EE) of 1,2-dichloro-4-fluorobenzene could be determined to be 35 714 +/- 2 cm(-1) while the MATI spectra yielded the adiabatic ionization energy (IE) of 1,2-dichloro-4-fluorobenzene which could be determined to be 73 332 +/- 7 cm(-1). PMID- 26884270 TI - Cancer of the uterus and treatment of stress incontinence: a pilot study. PMID- 26884271 TI - Restrictive bariatric procedures improve pregnancy outcomes compared with malabsorptive procedures. PMID- 26884267 TI - Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95. AB - The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes synaptic receptors, ion channels, structural proteins, and signaling molecules required for normal synaptic transmission and synaptic function. The scaffolding and hub protein postsynaptic density protein-95 (PSD-95) is a major element of central chemical synapses and interacts with glutamate receptors, cell adhesion molecules, and cytoskeletal elements. In fact, PSD-95 can regulate basal synaptic stability as well as the activity-dependent structural plasticity of the PSD and, therefore, of the excitatory chemical synapse. Several studies have shown that PSD-95 is highly enriched at excitatory synapses and have identified multiple protein structural domains and protein-protein interactions that mediate PSD-95 function and trafficking to the postsynaptic region. PSD-95 is also a target of several signaling pathways that induce posttranslational modifications, including palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation; these modifications determine the synaptic stability and function of PSD-95 and thus regulate the fates of individual dendritic spines in the nervous system. In the present work, we review the posttranslational modifications that regulate the synaptic localization of PSD-95 and describe their functional consequences. We also explore the signaling pathways that induce such changes. PMID- 26884272 TI - Trainee participation and perioperative complications in benign hysterectomy: the effect of route of surgery. AB - BACKGROUND: Intraoperative trainee involvement in hysterectomy is common. However, the effect of intraoperative trainee involvement on perioperative complications depending on surgical approach is unknown. OBJECTIVE: To estimate the effect of intraoperative trainee involvement on perioperative complication after vaginal, laparoscopic, and abdominal hysterectomy for benign disease. METHODS: Patients undergoing laparoscopic, vaginal, or abdominal hysterectomy for benign disease from 2010 to 2012 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients with and without trainee involvement were compared with regard to perioperative complications. Complications that occurred from the start of surgery to 30-days postoperatively were included. Perioperative complications were defined via the use of the validated Clavien-Dindo scale with >=grade 3 complications defined as major and <=grade 2 complications defined as minor. Major complications included myocardial infarction, pneumonia, venous thromboembolism, deep or organ space surgical-site infection, stroke, fascial dehiscence, unplanned return to the operating room, renal failure, cardiopulmonary arrest, sepsis, intubation greater than 48 hours, and death. Minor complications included urinary tract infection, blood transfusion, and superficial wound infection. To estimate the effect of trainee involvement depending on route of surgery, a stratified analysis was performed. Bivariable analysis and adjusted multivariable logistic regression were used. RESULTS: We identified 22,499 patients, of whom 42.1% had trainee participation. Surgical approaches were vaginal (22.7%), abdominal (47.1%), and laparoscopic (30.2%). The rate of major complication was 3.2%, and minor complication was 7.2%. In bivariable analysis, trainee involvement was associated with major complications in vaginal hysterectomy (3.3% vs 2.3%, P = .03), but not laparoscopic (3.0% vs 2.9%, P = .78) or abdominal hysterectomy (4.4% vs 3.6%, P = .07). Trainee involvement was also associated with minor complication in vaginal (7.3% vs 5.4%, P = .007), laparoscopic (5.9% vs 4.3%, P < .001), and abdominal hysterectomy (14.1% vs 9.2%, P < .001). In a multivariable analysis in which we adjusted for age, body mass index, medical comorbidity, American Society of Anesthesiologists score, and surgical complexity, the association between trainee involvement in vaginal hysterectomy and major complication persisted (adjusted odds ratio 1.45, 95% confidence interval 1.03-2.04); however, when operative time was added to the model, there was no longer an association between trainee involvement and major complication (adjusted odds ratio 1.26, 95% confidence interval 0.89-1.80). CONCLUSION: Surgical approach influences the relationship between trainee involvement and perioperative complication. Operative time is a key mediator of the relationship between trainee involvement and complication, and may be a modifiable risk factor. PMID- 26884273 TI - Reply. PMID- 26884274 TI - Sources of variation in hair cortisol in wild and captive non-human primates. AB - Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. PMID- 26884276 TI - Glial progenitor cell migration promotes CNS axon growth on functionalized electroconducting microfibers. AB - Electroactive systems that promote directional axonal growth and migration of glial progenitor cells (GPC) are needed for the treatment of neurological injuries. We report the functionalization of electroconducting microfibers with multiple biomolecules that synergistically stimulate the proliferation and migration of GPC, which in turn induce axonal elongation from embryonic cerebral cortex neurons. PEDOT doped with poly[(4-styrenesulfonic acid)-co-(maleic acid)] was synthesized on carbon microfibers and used for covalent attachment of molecules to the electroactive surface. The molecular complexes that promoted GPC proliferation and migration, followed by axonal extension, were composed of polylysine, heparin, basic fibroblast growth factor (bFGF), and matricellular proteins; the combination of bFGF with vitronectin or fibronectin being indispensable for sustained glial and axonal growth. The rate of glial-induced axonal elongation was about threefold that of axons growing directly on microfibers functionalized with polylysine alone. Electrical stimuli applied through the microfibers released bFGF and fibronectin from the polymer surface, consequently reducing GPC proliferation and promoting their differentiation into astrocytes, without causing cell detachment or toxicity. These results suggest that functionalized electroactive microfibers may provide a multifunctional tool for controlling neuron-glia interactions and enhancing neural repair. STATEMENT OF SIGNIFICANCE: We report a multiple surface functionalization strategy for electroconducting microfibers (MFs), in order to promote proliferation and guided migration of glial precursor cells (GPC) and consequently create a permissive substrate for elongation of central nervous system (CNS) axons. GPC divided and migrated extensively on the functionalized MFs, leading to fast elongation of embryonic cerebral cortex axons. The application of electric pulses thorough the MFs controlled glial cell division and differentiation. The functionalized MFs provide an advanced tool for neural tissue engineering and for controlling neuron glial interactions. CNS axonal growth associated to migratory glial precursors, together with the possibility of directing glial differentiation by electrical stimuli applied through the MFs, open a new research avenue to explore for CNS repair. PMID- 26884275 TI - Genome-wide mosaicism within Mycobacterium abscessus: evolutionary and epidemiological implications. AB - BACKGROUND: In mycobacteria, conjugation differs from the canonical Hfr model, but is still poorly understood. Here, we quantified this evolutionary processe in a natural mycobacterial population, taking advantage of a large clinical strain collection of the emerging pathogen Mycobacterium abscessus (MAB). RESULTS: Multilocus sequence typing confirmed the existence of three M. abscessus subspecies, and unravelled extensive allelic exchange between them. Furthermore, an asymmetrical gene flow occurring between these main lineages was detected, resulting in highly admixed strains. Intriguingly, these mosaic strains were significantly associated with cystic fibrosis patients with lung infections or chronic colonization. Genome sequencing of those hybrid strains confirmed that half of their genomic content was remodelled in large genomic blocks, leading to original tri-modal 'patchwork' architecture. One of these hybrid strains acquired a locus conferring inducible macrolide resistance, and a large genomic insertion from a slowly growing pathogenic mycobacteria, suggesting an adaptive gene transfer. This atypical genomic architecture of the highly recombinogenic strains is consistent with the distributive conjugal transfer (DCT) observed in M. smegmatis. Intriguingly, no known DCT function was found in M. abscessus chromosome, however, a p-RAW-like genetic element was detected in one of the highly admixed strains. CONCLUSION: Taken together, our results strongly suggest that MAB evolution is sporadically punctuated by dramatic genome wide remodelling events. These findings might have far reaching epidemiological consequences for emerging mycobacterial pathogens survey in the context of increasing numbers of rapidly growing mycobacteria and M. tuberculosis co-infections. PMID- 26884277 TI - Elucidating the role of free polycations in gene knockdown by siRNA polyplexes. AB - Future improvements of non-viral vectors for siRNA delivery require better understanding of intracellular processing and vector interactions with target cells. Here, we have compared the siRNA delivery properties of a lipid derivative of bPEI 1.8kDa (DOPE-PEI) with branched polyethyleneimine (bPEI) with average molecular weights of 1.8kDa (bPEI 1.8kDa) and 25kDa (bPEI 25kDa). We find mechanistic differences between the DOPE-PEI conjugate and bPEI regarding siRNA condensation and intracellular processing. bPEI 1.8kDa and bPEI 25kDa have similar properties with respect to condensation capability, but are very different regarding siRNA decondensation, cellular internalization and induction of reporter gene knockdown. Lipid conjugation of bPEI 1.8kDa improves the siRNA delivery properties, but with markedly different formulation requirements and mechanisms of action compared to conventional PEIs. Interestingly, strong knockdown using bPEI 25kDa is dependent on the presence of a free vector fraction which does not increase siRNA uptake. Finally, we have investigated the effect on lysosomal pH induced by these vectors to elucidate the differences in the proton sponge effect between lipid conjugated PEI and conventional PEI: Neither DOPE-PEI nor bPEI 25kDa affected lysosomal pH as a function of time, underlining that the possible proton sponge effect is not associated with changes in lysosomal pH. STATEMENT OF SIGNIFICANCE: Gene silencing therapy has the potential to treat diseases which are beyond the reach of current small molecule-based medicines. However, delivery of the small interfering RNAs (siRNAs) remains a bottleneck to clinical implementation, and the development of safe and efficient delivery systems would be one of the most important achievements in medicine today. A major reason for the lack of progress is insufficient understanding of cell polyplex interaction. We investigate siRNA delivery using polyethyleneimine (PEI) based vectors and examine how crucial formulation parameters determine the challenges associated with PEI as a delivery vector. We further evaluate how lipid conjugation of PEI influences formulation, cytotoxicity and polymer interaction with cells and cargo as well as the proton sponge capabilities of the vectors. PMID- 26884278 TI - Hierarchical self-assembly of magnetic nanoclusters for theranostics: Tunable size, enhanced magnetic resonance imagability, and controlled and targeted drug delivery. AB - Nanoparticle-based imaging and therapy are of interest for theranostic nanomedicine. In particular, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) have attracted much attention in cancer imaging, diagnostics, and treatment because of their superior imagability and biocompatibility (approved by the Food and Drug Administration). Here, we developed SPIO nanoparticles (NPs) that self assembled into magnetic nanoclusters (SAMNs) in aqueous environments as a theranostic nano-system. To generate multi-functional SPIO NPs, we covalently conjugated beta-cyclodextrin (beta-CD) to SPIO NPs using metal-adhesive dopamine groups. Polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the beta-CD cavity through high affinity complexation. The core-shell structure of the magnetic nanoclusters was elucidated based on the condensed SPIO core and a PEG shell using electron microscopy and the composition was analyzed by thermogravimetric analysis (TGA). Our results indicate that nanocluster size could be readily controlled by changing the SPIO/PEG ratio in the assemblies. Interestingly, we observed a significant enhancement in magnetic resonance contrast due to the large cluster size and dense iron oxide core. In addition, tethering a tumor-targeting peptide to the SAMNs enhanced their uptake into tumor cells. PTX was efficiently loaded into beta-CDs and released in a controlled manner when exposed to competitive guest molecules. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy. STATEMENT OF SIGNIFICANCE: In this study, we developed multi-functional SPIO NPs that self-assembled into magnetic nanoclusters (SAMNs) in aqueous conditions as a theranostic nano-system. The beta-cyclodextrin (beta-CD) was immobilized on the surfaces of SPIO NPs and RGD-conjugated polyethylene glycol (PEG) and paclitaxel (PTX) were hosted in the beta-CD cavity through high affinity complexation. We found that nanocluster size could be readily controlled by varying the SPIO/PEG ratio in the assemblies, and also demonstrated significant improvement of the functional nanoparticles for theranostic systems; enhanced magnetic resonance, improved cellular uptake, and efficient PTX loading and sustained release at the desired time point. These results strongly indicate that the SAMNs developed in this study possess great potential for application in image-guided cancer chemotherapy. PMID- 26884279 TI - High throughput approaches for controlled stem cell differentiation. AB - Stem cells have unique ability to undergo self-renewal indefinitely in culture and potential to differentiate into almost all cell types in the human body. However, the developing a method for efficiently differentiating or manipulating these stem cells for therapeutic purposes remains a challenging problem. Pluripotent stem cells, as well as adult stem cells, require biological cues for their proliferation and differentiation. These cues are largely controlled by cell-cell, cell-insoluble factors (such as extracellular matrix), and cell soluble factors (such as cytokine or growth factors) interactions. In this review, we describe a state of research on various stem cell-based tissue engineering applications and high throughput strategies for developing synthetic or biosynthetic microenvironments to allow efficient commitments in stem cells. STATEMENT OF SIGNIFICANCE: Nowadays, pluripotency of stem cells have received much attention to use therapeutic purpose. However, a major difficulty with stem cell therapy is to control its differentiation through desired cells or tissues. In other words, various microenvironment factors are involved during stem cell differentiation, including dimensionality, growth factors, cell junctions, nutritional status, matrix stiffness, matrix composition, mechanical stress, and cell-matrix adhesion. Therefore, researchers have engineered a variety of platforms to enable controlling and monitoring bioactive factors to induce stem cell commitment. In this review, we report on recent advancements in a novel technology based on high-throughput strategies for stem cell-based tissue engineering applications. PMID- 26884280 TI - 2016 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference. PMID- 26884281 TI - Bioanalytical techniques in discrimination between therapeutic and abusive use of drugs in sport. AB - The discrimination between therapeutic and abusive use of drugs in sports is performed using threshold concentrations or reporting levels, and the detection of the substances in a sample is only reported as an adverse analytical finding when the concentration exceeds the threshold or the reporting level. In this paper, the strategies of discrimination and the analytical methods used for the main groups of substances where the distinction is needed (beta-2 agonists, ephedrines, glucocorticoids and morphine) will be reviewed. Nowadays, LC-MS is the method of choice for the analysis of these substances and, in most of the cases, a simple dilution of the urine sample is performed before the chromatographic analysis. PMID- 26884283 TI - Subtotal parathyroidectomy versus total parathyroidectomy with autotransplant in secondary hyperparathyroidism - a single-centre prospective cohort of 43 patients. AB - INTRODUCTION: The need for parathyroidectomy remains high in the group of patients on long-term dialysis with medically refractory secondary hyperparathyroidism (sHPT). We aim to compare the results after subtotal parathyroidectomies (sPtx) and total parathyroidectomies with autotransplant (tPtx + AT) performed for sHPT at a single referral centre. MATERIAL AND METHODS: This prospective study comparatively analysed sPtx and tPtx + AT performed in our department between February 2010 and December 2014. We followed-up both surgical techniques, with respect to the main clinical symptoms, laboratory data, mortality, and recurrent disease. RESULTS: Forty-three patients on whom we performed 26 sPtx and 19 tPtx + AT were entered in the study. There were no statistically significant differences between groups as far as demographic and preoperative clinical data are concerned. We did not encounter postoperative mortality in either of the groups. The follow-up period was significantly longer for the sPtx group (p = 0.04). The immediate postoperative serum calcium levels were significantly lower in the tPtx + AT group (p = 0.009). Definitive hypoparathyroidism was encountered in two patients in the sPtx group (8.3%) and in one from the tPtx + AT group (5.26%). Four patients from the sPtx group (16.6%) and three from the tPtx + AT group (15.78%) died during the follow-up due to causes unrelated to parathyroidectomy. Overall we had two recurrences in the sPtx group and none in the tPtx + AT group (p = 0.57). CONCLUSIONS: In our opinion both techniques have comparable results concerning the clinical and laboratory outcomes and rates of postoperative hypoparathyroidism, at least in short- and medium-term follow-up. PMID- 26884282 TI - Increased Risk of Depression Recurrence After Initiation of Prescription Opioids in Noncancer Pain Patients. AB - Several studies have shown that chronic opioid analgesic use is associated with increased risk of new-onset depression. It is not known if patients with remitted depression are at increased risk of relapse after exposure to opioid analgesics. A retrospective cohort design using patient data from the Veterans Health Administration (VHA; n = 5,400), and Baylor Scott & White Health (BSWH; n = 842) was performed with an observation period in the VHA from 2002 to 2012 and in the BSWH from 2003 to 2012. Eligible patients had a diagnosis of depression at baseline and experienced a period of remission. Risk of depression recurrence was modeled in patients that either started taking an opioid or continued without opioid prescriptions before or during remission. Cox proportional hazard models were used to measure the association between opioid use and depression recurrence controlling for pain, and other confounders. Patients exposed to an opioid compared with those unexposed had a significantly greater risk of depression recurrence in both patient populations (VHA: hazard ratio [HR] = 2.17, 95% confidence interval [CI], 2.01-2.34; BSWH: HR = 1.77; 95% CI, 1.42-2.21). These results suggest opioid use doubles the risk of depression recurrence even after controlling for pain, psychiatric disorders, and opioid misuse. Further work is needed to determine if risk increases with duration of use. Repeated screening for depression after opioid initiation may be warranted. PERSPECTIVE: In 2 large patient cohorts with large differences in demographic characteristics and comorbidity, patients with remitted depression who were exposed to opioid analgesics were 77% to 117% more likely to experience a recurrence of depression than those who remained opioid -free. Routine, not just at initiation of treatment, screening for depression is warranted. PMID- 26884284 TI - Assessment of OPG, RANKL, bone turnover markers serum levels and BMD after treatment with strontium ranelate and ibandronate in patients with postmenopausal osteoporosis. AB - INTRODUCTION: The aim of this study was to evaluate quantitative changes in OPG and RANKL proteins after treatment with strontium ranelate (SR) and ibandronate in patients with postmenopausal osteoporosis. MATERIAL AND METHODS: A total of 89 women with postmenopausal osteoporosis (PO), aged 51-85 years, patients of the Outpatient Clinic of Osteoporosis of the Military Teaching Hospital in Lodz, were enrolled in the study. The patients were randomly assigned to different therapies: ibandronate and (SR). Patients of the control group received only calcium and vitamin D3 supplements. The patients' visits were repeated after three and six months. Measurements of beta-CTX (C-terminal Telopeptide of type 1 collagen), osteocalcin, RANKL, osteoprotegerin (OPG), alkaline phosphatase concentrations in serum, as well as of total 24-hour calcium and phosphate levels in serum and urine, were carried out in material collected at baseline and after three and six months of therapy. Left hip and lumbar spine densitometry was done twice (at baseline visit and after six months). RESULTS: In all three groups there were no significant differences noted in the concentrations of OPG and RANKL serum protein levels during the study period. Both negative and positive correlations or tendencies of correlations were found between OPG serum concentrations and BMD changes in the SR group. CONCLUSIONS: Both ibandronate and SR do not seem to cause any significant changes in OPG and RANKL protein serum levels during the first six months of treatment. OPG may play a role in osteoclast activity suppression in the course of treatment with ibandronate in patients with PO. OPG may play an important role in the mechanism of SR therapy and may be viewed as a potentially valuable parameter for monitoring and predicting the course of treatment with SR in PO. PMID- 26884285 TI - Falls in RAC-OST-POL Study: epidemiological study in postmenopausal women aged over 55 years. AB - INTRODUCTION: Falls are often noted in elderly women. They may have serious clinical consequences. The aim of the study is the presentation of epidemiological data on falls in postmenopausal women. MATERIAL AND METHODS: A total of 978 women in mean age 65.9 +/- 7.6 years from the population of Raciborz district were included. In a questionnaire the following data were gathered: falls in last 12 months, place of stay, kind of job, marital status, education, smoking, underlying diseases, and used medications. RESULTS: Falls occurred in 328 women (33.5%). The number of falls correlated positively with increasing age, (r = 0.13, p < 0.0001). The falls rate was not related to weight and height, but weak, significant correlation with body mass index was noted (r = 0.076, p< 0.05). Among 286 women with prior osteoporotic fracture falls were present in 40.9%, which was significantly more than the 30.4% seen in women without fracture (Chi-square test; 10.05; df = 1; p < 0.01). Falls were fewer often among women from the city of Raciborz (29.8%) than in women from the rural population (39.7%). After adjustment for age, rural stay, diabetes type 1, renal failure, rheumatoid arthritis, bronchial asthma, and depression revealed influence on falls occurrence. As was shown by logistic regression, age, rural stay, prior fracture, diabetes type 1, bronchial asthma, and depression increased the risk of fall. The cumulative number of these risk factors correlated with the number of falls (r = 0.22, p < 0.000001). CONCLUSIONS: Falls are common among postmenopausal women, and their occurrence is modified by several factors including age, place of stay, and some co-morbidities. PMID- 26884287 TI - Endocrine autoimmunity in patients with Latent Autoimmune Diabetes in Adults (LADA) - association with HLA genotype. AB - INTRODUCTION: Latent autoimmune diabetes in adults (LADA) is a slow-developing form of autoimmune diabetes, characterised by the presence of type 1 diabetes associated autoantibody and presentation at diagnosis similar to patients with type 2 diabetes. The aim of this study was to determine the prevalence of auto antibodies related to endocrine autoimmune diseases in patients with LADA and to assess their association with HLA genotype. MATERIAL AND METHODS: We evaluated the presence of anti-thyroglobulin (ATG), anti-thyroid peroxidase (ATPO), anti tissue transglutaminase IgA (ATTA), and anti 21 hydroxylase (A21H) in 70 patients with LADA, 69 with Type 2 diabetes, and in 50 healthy controls HLA genotype was assed in subpopulation of sluclied subjects. RESULTS: The presence of ATPO (28.6 vs. 10%); ATG (28.6 vs. 14%) was higher in patients with LADA in comparison to healthy controls and ATPO in comparison to patients with type 2 diabetes (38.6 vs. 17.4 %). In patients with LADA the presence of autoimmune thyroid autoantibodies was associated with newly diagnosed subclinical hypothyroidism; almost 7% of patients presented with high TSH. The presence of A21H (2.86 vs. 5.8 vs. 6.1%) and ATTA (2.86 vs. 4.3 vs. 6.0%) was not different between groups. Patients with high TSH level were positive for DQA1*0301 and DRB1*04 HLA genotype: DQB1*0201 and DQB1*02 were higher in patients positive for ATTA. CONCLUSIONS: Patients with LADA have higher prevalence of thyroid autoimmune diseases. In patients with LADA similarly to type 1 genotype DQA1*0301 seems to CONFER susceptibility to thyroid autoimmunity, and DQB1*0201 to celiac disease. PMID- 26884286 TI - Fibroblast growth factor 21 and its relationship with insulin sensitivity in first-degree relatives of patients with type 2 diabetes mellitus. AB - INTRODUCTION: Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). RESULTS: There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 +/- 93.8, 221.9 +/- +/- 171.7 and 121.2 +/- 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = -0.24, p = 0.02) and Matsuda ISI (r = -0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r2 = 0.17, p < 0.001). CONCLUSIONS: We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity. (Endokrynol Pol 2016; 67 (3): 260-264). PMID- 26884288 TI - Complete recovery of visual acuity as the main goal of treatment in patients with dysthyroid optic neuropathy. AB - INTRODUCTION: To evaluate the effectiveness of methylprednisolone (MP) and surgical treatment in achieving complete reversal of dysthyroid optic neuropathy (DON) and predictive factors of this therapy. MATERIAL AND METHODS: The group consisted of 10 patients (18 eyes) with DON. The diagnosis of DON was based on at least two criteria from the following: (i) deterioration of visual acuity (VA< 1.0), (ii) loss of colour vision, (iii) optic disc swelling, and/or (iv) signs of DON in magnetic resonance imaging (presence of apical crowding and/or optic nerve stretching). A complete recovery of DON was defined as the normalisation of VA (VA = 1.0), normal colour vision, and reversal of optic disc swelling. A significant improvement was defined as improvement of VA of at least 0.2. The consecutive steps of treatment of DON consisted of: (i) first-line treatment - intravenous MP pulse therapy (3 * 1 g); (ii) second-line treatment - endoscopic intranasal orbital decompression of medial wall; (iii) additional treatment - additional MP therapy and/or surgical decompression. RESULTS: A significant improvement in VA could be achieved in the majority of patients; a complete recovery was noted in 22.2%, 33.3%, and 66.7% of eyes after first-line, second line, and additional treatment, respectively. Positive predictive factors were: younger age (p = 0.049), shorter duration of DON (p = 0.035), and a higher Graves' orbitopathy clinical activity score (p = 0.035). CONCLUSIONS: By using combination therapy (intravenous MP pulse therapy and surgical decompression), a complete recovery can be achieved in the majority of patients with DON. PMID- 26884289 TI - Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels. AB - INTRODUCTION: Lipid-lowering agents affect adipose tissue function. No study has investigated the role of age in the effects of hypolipidaemic agents on plasma adipokines. MATERIAL AND METHODS: The study was a retrospective analysis of data of 65 hypercholesterolaemic patients treated for 90 days with simvastatin, ezetimibe, or simvastatin/ezetimibe combination therapy. Circulating levels of leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha), as well as high-sensitivity C-reactive protein (hsCRP) were assessed separately for patients aged between 35 and 50 years and between 51 and 65 years, at the beginning and at the end of treatment. RESULTS: Patients in the age between 51 and 65 years had higher plasma levels of TNF-alpha and hsCRP, and lower plasma levels of adiponectin than patients aged between 35 and 50 years. In both age groups, simvastatin reduced plasma levels of hsCRP, leptin, visfatin, and TNF alpha and increased circulating levels of adiponectin. This effect was particularly pronounced if simvastatin was administered in combination with ezetimibe. Ezetimibe alone increased plasma adiponectin and reduced plasma levels of leptin and hsCRP only in older adults. Irrespectively of age, ezetimibe administered alone did not affect visfatin and TNF-alpha. The effect of simvastatin on plasma hsCRP and the investigated adipokines did not differ between both groups. In turn, the effect of ezetimibe and simvastatin/ezetimibe combination therapy on leptin, adiponectin, and hsCRP was stronger in older than in younger adults. CONCLUSIONS: Our results show that age may partially determine the effect of ezetimibe, but not of simvastatin, on adipose tissue function. (Endokrynol Pol 2016; 67 (3): 271-276). PMID- 26884290 TI - The effect of hypolipidemic treatment on monocyte cytokine release in different age groups of patients with type 2 diabetes and atherogenic dyslipidemia. AB - INTRODUCTION: Although both statins and fibrates have been found to reduce monocyte cytokine release, no study has investigated whether the effect of hypolipidaemic agents depends on age. MATERIAL AND METHODS: This study retrospectively analysed the results of 65 patients with type 2 diabetes and atherogenic dyslipidaemia, complying with lifestyle intervention, and receiving metformin. These patients were then treated with simvastatin (40 mg daily), micronized fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Tumour necrosis factor-alpha (TNF-alpha), inteleukin-1beta, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1) release, as well as circulating levels of high sensitivity C-reactive protein (hsCRP), were determined separately for patients aged between 20 and 50 years and between 51 and 75 years before the study and after 12 weeks of hypolipidaemic treatment. RESULTS: Older adults were characterised by higher monocyte release of TNF-alpha and interleukin-6, as well as higher circulating levels of hsCRP, than the younger subjects. The decrease in monocyte release of all investigated cytokines and in plasma hsCRP was similar in both age groups. In turn, the effect of fenofibrate, alone or in combination with simvastatin, on TNF-alpha, interleukin-6, and hsCRP, but not on interleukin-1beta and MCP-1, was stronger in patients aged between 50 and 75 years, and correlated with an improvement in insulin sensitivity only in this age group. CONCLUSIONS: Our results suggest that age may partially determine monocyte-suppressing and systemic anti-inflammatory effects of fenofibrate. PMID- 26884291 TI - Evaluation of lipid profiles in patients with metabolic syndrome according to cardiovascular risk calculated on the basis of the SCORE chart. AB - INTRODUCTION: Metabolic syndrome predicts the development of CVD. Lipid abnormalities probably have an important influence on the increase of cardiovascular death risk. The SCORE chart includes only total cholesterol level, which may be inadequate. The aim of our study was to evaluate the lipid profile in patients with metabolic syndrome according to the cardiovascular risk calculated on the basis of the SCORE chart. MATERIAL AND METHODS: The study participants comprised 974 patients with metabolic syndrome. The 10-year death risk of cardiovascular disease was calculated on the basis of SCORE chart in all patients. The study group was divided in three subgroups depending on the risk level calculated by SCORE scale. RESULTS: There was a significantly higher level of LDL-C fraction in the subgroup of very high CV risk in comparison to the group of medium and high CV risk. The level of non-HDL-C was also significantly higher in the group with SCORE >= 10 compared to the remaining subgroups of medium and high CV risk. CONCLUSIONS: Increased CV risk in this group of patients may be associated not only with higher TC level, but also the other lipid fractions. The assessment of the CV risk on the basis of the SCORE chart, which includes only TC level, may be inadequate. A modification of the SCORE chart for the European population should be considered (inclusion of LDL-C level, or in selected cases non-HDL-C level instead of TC level). (Endokrynol Pol 2016; 67 (3): 265-270). PMID- 26884292 TI - The effects of fat distribution and some adipokines on insulin resistance. AB - INTRODUCTION: The risk of developing insulin resistance and metabolic syndrome is particularly high in central obesity. In this study we evaluated the effects of fat distribution and some adipokines on insulin resistance in prediabetic patients. MATERIAL AND METHODS: Eighty-seven age- and sex-matched patients were divided into three groups according to their 75-gram oral glucose tolerance test results as follows: impaired fasting glucose group, impaired glucose tolerance group, and normal glucose tolerance group. Fasting insulin levels were measured. Homeostatic model assessment of insulin resistance was calculated. Body fat mass measurements were assessed by bioelectric impedance analyser and abdominal fat thicknesses (subcutaneous, visceral, and preperitoneal) by ultrasonography. The fasting serum levels of several adipokines [adiponectin, leptin, resistin, vaspin, visfatin, retinol-binding protein-4 (RBP-4), tumour necrosis factor-alpha (TNF-alpha)] were measured by ELISA method. RESULTS: The mean body mass index, fat mass measurements, and abdominal fat thicknesses of the groups were similar. There were no differences between groups in terms of the mean fasting insulin, vaspin, RBP-4, leptin, resistin, and TNF-alpha. In comparison of the prediabetic and normal groups, the levels of adiponectin (p < 0.001) and visfatin (p < 0.001) were lower in the prediabetic group. Furthermore, we found that high body mass index (p < 0.01) and fat mass (p < 0.01) and low adiponectin (p < 0.05) levels have roles in the development of insulin resistance in the prediabetic group. CONCLUSIONS: We suggested that in the prediabetic period not only obesity but also decreased adiponectin levels play some role in the pathogenesis of insulin resistance. (Endokrynol Pol 2016; 67 (3): 277-282). PMID- 26884293 TI - Molecular classification of pituitary adenomas: in search for criteria useful for high-throughput studies. AB - INTRODUCTION: The mechanism of pathogenesis of pituitary adenomas is still unknown, and it shows differences in pituitary cells of different origin. The aim of our study was to analyse the gene expression profile of pituitary hormones and their precursor genes: PRL, GH, POMC, TSHb, LHb, FSHb, and CGA by QPCR in particular types of pituitary adenomas, and to evaluate the results in the context of sample selection for microarray studies. MATERIAL AND METHODS: Analysis of the gene expression profile was performed in 84 samples of pituitary adenomas, by real-time quantitative PCR (QPCR). RESULTS: As expected, expression of GH gene was significantly higher in somatotropinomas than in prolactinomas (p < 0.05). For POMC gene we noticed lower expression in all pituitary adenomas, except adrenocorticotropinomas (p < 0.05). In the case of PRL gene, the highest expression was observed; PRL+ adenomas were in third place. LHb and FSHb genes showed the highest expression, respectively, in LH-producing and FSH-producing pituitary adenomas; however, our analysis did not show statistically significant differences between LH-producing and FSH-producing adenomas. CONCLUSIONS: Our study showed that GH is a characteristic gene for somatotropinomas. We drew a similar conclusion for POMC gene and adrenocorticotropinomas. However, the results that we obtained for PRL, TSHb, LHb, FSHb, and CGA genes indicate that evaluation of gene expression is not sufficient for classification of particular subtypes of pituitary adenomas. PMID- 26884294 TI - Treatment of severe thyroid function disorders and changes in body composition. AB - INTRODUCTION: Hyper- and hypothyroidism are accompanied by altered metabolic rate, thermogenesis, and body weight. The aim of this study was to estimate the relation between treatment-induced changes in thyroid function, and the accompanying body composition in patients with either severe hypo- or hyperthyroidism. MATERIAL AND METHODS: Body composition analysis and hormonal assessment were measured at the initial diagnosis of thyroid disorder, after three-month treatment, and finally after complete recovery from hyperthyroidism (n = 18) or hypothyroidism (n = 27). Nonparametric Spearman correlation was used to analyse the relation between thyroid hormones and body composition as well as their respective changes. RESULTS: In hypothyroid patients applied treatment significantly reduced (p < 0.05) total body weight, mainly due to a decrease in fat mass, whereas in hyperthyroid patients it caused a weight gain, with a simultaneous increase in muscle, water and fat mass. Total body weight and fat mass were significantly correlated with thyroid hormones' concentrations in all patients. Changes of fat, water, or muscle mass were strongly correlated with the changes in the patients' hormonal status. CONCLUSIONS: Body composition is related to the concentration of thyroid hormones in thyroid dysfunction. Treatment-induced changes in thyroid hormones concentrations are correlated with the magnitude of the change of body weight, including muscle, water, and fat amount. (Endokrynol Pol 2016; 67 (4): 359-366). PMID- 26884295 TI - Differentiation of thyroid nodules in multinodular goiter with the application of technical ultrasound advances - initial results. AB - INTRODUCTION: To evaluate the relative value of technical ultrasound advances in differentiation of thyroid nodules in multinodular goitre. MATERIAL AND METHODS: The study included patients with multinodular goitre, who were referred for thyroidectomy. Ultrasound evaluation of suspicious nodules was performed with: improved B-mode (spatial compound imaging and differential tissue harmonics), dedicated mapping of microcalcifications, mapping of the nodule vessels, and strain elastography evaluated qualitatively and semi quantitatively. RESULTS: A total of 163 nodules in 124 patients with multinodular goitre were evaluated (147 benign and 16 cancers). Improved B-mode imaging was: 76.76% sensitive and 62.5% specific with AUC 0.740. Differentiating B-mode features were: shape - taller than wide OR 15.8, markedly hypoechoic OR 14.7, absence of cystic areas OR 6.6, absence of halo OR 5.0, and blurred/microlobulated margins OR 3.7. Addition of MicroPure imaging was 80.28% sensitive and 68.75% specific with AUC 0.771. MicroPure alone, power Doppler, and strain elastography were not statistically significant. CONCLUSIONS: Among singular modes of ultrasound imaging, only improved B-mode imaging proved to have a significant role in differentiation of thyroid nodules in multinodular goitre. Additional gain was seen with the addition to B-mode of the mapping of microcalcifications with MicroPure imaging. Power Doppler and strain elastography did not prove to be useful techniques in multinodular goitre. PMID- 26884296 TI - Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes. AB - INTRODUCTION: Paraoxonase 1 (PON1) polymorphisms have been largely involved in diabetes complications. The aim of the study is to evaluate the effects of PON1 polymorphisms (L55M and Q192R) on diabetic nephropathy (DN). MATERIAL AND METHODS: The study involved 116 children and adolescents with type 1 diabetes (T1D) and 91 healthy subjects. Albumin excretion rate (AER) was determined by immunoturbidimetry. PON1 activity was measured by a spectrophotometric method, and genotyping of PON1 gene was assessed by multiplex PCR followed by RFLP. RESULTS: PON1 activity was inversely correlated to AER (r = -0.245, p = 0.008). A significant decrease (p = 0.037) in PON1 activity was shown between patients with nephropathy and those without (162 [57-618] vs. 316 [37-788] IU/L, respectively). The distribution of AER was, for L55M polymorphism MM > LM > LL (p = 0.002), and for Q192R polymorphism QQ > QR > RR (p < 0.001). The opposite distribution was noted for PON 1 activity (p < 0.001). LMQQ and MMQQ haplotypes seem to increase AER (p = 0.004, p = 0.003, respectively) and to reduce PON1 activity (p = 0.011, p = 0.052, respectively) in youths with T1D. However, LLRR haplotype seems to have the opposite effect. CONCLUSIONS: This study demonstrated that PON1 polymorphisms L55M and Q192R seem to be genetic markers involved in the development of DN in T1D. (Endokrynol Pol 2017; 68 (1): 35-41). PMID- 26884297 TI - The diagnostic value of late-night salivary cortisol for diagnosis of subclinical Cushing's syndrome. AB - INTRODUCTION: Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC). MATERIAL AND METHODS: The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 MUg/dL and ACTH < 10 pg/mL. RESULTS: Mean late-night salivary cortisol levels in subjects with subclinical Cushing's syndrome were significantly higher than in subjects with non functioning adrenal adenoma and the control group (p < 0.001). Using a cut-off value of 0.18 MUg/dL, the sensitivity and specificity of late-night salivary cortisol for diagnosing subclinical Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 MUg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively. CONCLUSIONS: Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492). PMID- 26884298 TI - The effect of sleeve gastrectomy on serum irisin levels in patients with morbid obesity. AB - INTRODUCTION: Irisin, a recently identified myokine, is associated with increased energy expenditure and has a potential role in obesity. Therefore, we investigated circulating irisin levels in morbidly obese patients undergoing sleeve gastrectomy (SG). MATERIAL AND METHODS: Thirty morbidly obese patients undergoing SG and 30 healthy subjects were included. All participants were evaluated at baseline and again at three months post-SG. Body weight and height, the lipid profile, and plasma glucose, HbA1c, insulin, and irisin levels were measured at each visit. RESULTS: The two groups had similar mean age and sex distribution. Serum irisin was significantly lower in the morbidly obese subjects compared with the controls (p = 0.003) and negatively correlated with BMI, body weight, insulin levels, and HOMA-IR (p = 0.006, p = 0.011, p = 0.046, p = 0.048, respectively). When the morbidly obese patients were re-evaluated three months post-SG, their weight and BMI had significantly decreased (both p = 0.001). Similarly, the insulin, HbA1c, HDL-cholesterol, and HOMA-IR values significantly decreased (p = 0.001, p = 0.028, p = 0.006, and p = 0.001, respectively). However, irisin levels remained unchanged (p = 0,267). CONCLUSION: Although the irisin levels were significantly lower in the morbidly obese subjects, they did not change after SG-induced weight loss. (Endokrynol Pol 2016; 67 (5): 481-486). PMID- 26884300 TI - The impact of diabetes mellitus on the survival of patients with acromegaly. AB - INTRODUCTION: An increased risk of mortality in patients with uncontrolled acromegaly has been reported in several studies. We aimed to assess the impact of co-morbidities on the survival of patients with acromegaly after long-term treatment and follow-up. MATERIAL AND METHODS: A retrospective analysis was performed for 285 patients with active acromegaly, who were admitted to the Chang Gung Memorial Hospital, Taiwan between 1978 and 2012. Of these patients, 106 (37.2%) were diagnosed with diabetes mellitus (DM). During the follow-up period, 21 cases of histological proved malignant in acromegalic patients, and DM with acromegaly had a higher incidence of malignancy (13.2% vs. 3.8%; p < 0.01). The 5 , 10-, and 20-year survival rates were 93.1%, 86.9%, and 84.7% for the DM group, respectively, and 96.5%, 96.5%, and 96.5% for the non-DM group, respectively. After a mean follow-up of 15.1 +/- 0.6 years, age, DM, coronary heart disease, and malignancy were found to be significant factors of mortality. Control of growth hormone and IGF-1 levels also conferred a marginal survival benefit. CONCLUSIONS: DM and malignancy significantly influence the survival of patients with acromegaly; thus, these patients need close follow-up and appropriate therapy. (Endokrynol Pol 2016; 67 (5): 501-506). PMID- 26884299 TI - Time-dependent irisin concentration changes in patients affected by overt hypothyroidism. AB - INTRODUCTION: Irisin, a cleaved and secreted part of the transmembrane protein FNDC5, is a recently discovered adipo-myokine that is said to have a significant influence on body metabolism. Changes in thyrometabolic state may also alter the serum irisin level. Since already reported data are not fully consistent, the aim of the present research is to evaluate the time-dependent changes in serum irisin level in patients affected by overt hypothyroidism. MATERIAL AND METHODS: The study involved 36 subjects - two groups of 12 patients with long-lasting (AITD) and short-term (TC) overt hypothyroidism, and a control group (CG) of 12 subjects, matched for age and gender. Serum irisin level, thyrometabolic state, creatine kinase (CK - muscle damage marker), glucose, and insulin concentration were assessed and compared between groups. RESULTS: The irisin level was significantly lower in AITD than in TC and CG (p = 0.02; p < 0.01; respectively) patients, with no statistical difference between TC and CG (p > 0.05). There was no significant difference between free triiodothyronine and free thyroxine levels in AITD and TC patients (p > 0.05). CK concentration was significantly higher in AITD than in CG patients (p < 0.01) with no difference between AITD and TC patients (p > 0.05) as well as TC and CG patients (p > 0.05). Additionally, the CK level negatively correlated with the irisin level (r = -0.58; p < 0.01). CONCLUSIONS: In conclusion, the irisin concentration changes during thyroid function impairment may be time-dependent. Patients with prolonged hypothyroidism have lower irisin levels that those with short-term disorder. (Endokrynol Pol 2016; 67 (5): 476-480). PMID- 26884301 TI - The pituitary-gonadal-thyroid and lactotroph axes in critically ill patients. AB - INTRODUCTION: The normal circadian rhythm of hormones in critical patients becomes chaotic causing some hormones to increase and others to decrease abnormally. The goal of this study is to evaluate hormonal changes in severely ill patients and to investigate the relationship between hormonal changes and mortality and morbidity. MATERIAL AND METHODS: We enrolled 20 patients (10 F/10 M). Blood samples were collected on day 0, day 5, and day 10. If a patient was discharged before these defined days, a sample was drawn on that day. Twenty healthy controls were included. RESULTS: Female patients had lower LH, FSH, and fT3 and higher PRL and cortisol levels than controls on admission to the intensive care unit (ICU) (pLH = 0.021, pFSH:0.001, pfT3 = 0.021, pPRL = 0.042, pCortisol <0.001, respectively). Men had significantly low testosterone and fT3, and high PRL and cortisol levels on ICU admission (pT = 0.01, pfT3 = 0.043, pPRL = 0.005, pCortisol < 0.001, respectively). The lowest levels of gonadotropins in both genders and testosterone in men were measured on day 5. Cortisol levels decreased in the patients discharged from the ICU (p = 0.01). FSH levels increased in recovered women (pFSH = 0.043). The mortality rate was 30%. There were correlations between admission TSH and NIMV duration (p = 0.006), fT3 and APACHE II (p = 0.001), and PRL and mortality (p = 0.044). Positive correlations between E2 and APACHE II (p = 0.003) in females, and PRL and APACHE II (p = 0.022) in males were also displayed. CONCLUSIONS: Critically ill patients develop significant changes in neuroendocrine axes. Alterations in hormones correlate with the disease severity and mortality. (Endokrynol Pol 2016; 67 (3): 305-312). PMID- 26884302 TI - The role of circulating sTWEAK in the pathogenesis of Hashimoto's thyroiditis - a pilot study. AB - INTRODUCTION: We aimed to investigate the role of sTWEAK in the pathogenesis of Hashimoto's thyroiditis, which is a chronic inflammatory autoimmune disease. MATERIAL AND METHODS: A total of 80 patients were included in the study, 60 of whom were newly diagnosed with Hashimoto's thyroiditis (20 patients in each of the euthyroid, subclinical hypothyroid, and overt hypothyroid subgroups), and 20 of whom were healthy volunteers. Thyroid function tests and autoantibodies were measured using the electro-chemiluminescence immunoassay method, and sTWEAK, IL 17A, IL-12, and TGF-beta1 were measured using enzyme-linked immunosorbent assay method. RESULTS: The Hashimoto's Thyroiditis group had lower levels of sTWEAK and TGF-beta1, but had higher levels of IL-12 and IL-17A as compared to the control group. Of these, only the difference between IL-17A levels reached statistical significance (2.1 pg/mL vs. 1.8 pg/mL, respectively; p < 0.001). While the levels of sTWEAK were similar in the control, euthyroid, and subclinical groups, the overt hypothyroidism group had lower level of sTWEAK than that of subclinical hypothyroidism (687.6 +/- 153.3 pg/mL vs. 888.2 +/- 374.4 pg/mL, respectively; p = 0.03). A negative correlation was determined between sTWEAK level and anti-TPO (r = -0.533, p = 0.028) and IL-17A (r = -0.600, p = 0.005) levels in the overt hypothyroidism group. CONCLUSIONS: The reduced levels of sTWEAK with progression of Hashimoto's Thyroiditis and the significant correlation between the sTWEAK levels and anti-TPO found in this study suggest that sTWEAK plays an active role in chronic inflammation in the pathogenesis of Hashimoto's Thyroiditis and in the progression of autoimmunity. (Endokrynol Pol 2016; 67 (6): 562-566). PMID- 26884303 TI - Cushing's disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study. AB - INTRODUCTION: Effective transsphenoidal surgery (TSS) for Cushing's disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. OBJECTIVE: A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. MATERIAL AND METHODS: Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. RESULTS: Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). CONCLUSIONS: Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291). PMID- 26884304 TI - The role of melatonin membrane receptors in melatonin-dependent oxytocin secretion from the rat hypothalamo-neurohypophysial system - an in vitro and in vivo approach. AB - INTRODUCTION: Melatonin exerts its biological role acting mainly via G protein coupled membrane MT1 and MT2 receptors. To determine whether a response of oxytocinergic neurons to different concentrations of melatonin is mediated through membrane MT1 and/or MT2 receptors, the effect of melatonin receptors antagonists, i.e. luzindole (a non-selective antagonist of both MT1 and MT2 receptors) and 4-phenyl-2-propionamidotetralin (4-P-PDOT - a selective antagonist of MT2 receptor), on melatonin-dependent oxytocin (OT) secretion from the rat hypothalamo-neurohypophysial (H-N) system, has been studied both in vitro and in vivo. MATERIAL AND METHODS: For in vitro experiment, male rats served as donors of the H-N explants, which were placed in 1 ml of normal Krebs-Ringer fluid (nKRF) heated to 37oC. The H-N explants were incubated successively in nKRF {fluid B1} and incubation fluid as B1 enriched with appropriate concentration of melatonin, i.e. 10-9 M, 10-7 M, or 10-3 M and luzindole or 4-P-PDOT, or their vehicles (0.1% ethanol or DMSO) {fluid B2}. After 20 minutes of incubation in fluid B1 and then B2, the media were collected and immediately frozen before OT estimation by the RIA. The OT secretion was determined by using the B2/B1 ratio for each H-N explant. During in vivo experiment, rats were given an intracerebroventricular (i.c.v.) infusion of 5 mL luzindole or 4-P-PDOT, or their solvent (0.1% DMSO) and 10 minutes later the next i.c.v. infusion of 5 mL of either melatonin solution (10-7 M) or its vehicle (0.1 % ethanol in 0.9% sodium chloride). RESULTS: Melatonin at a concentration of 10-3 M significantly stimulated, while at a concentration of 10-9 M had no effect on, oxytocin secretion from the rat H-N system in vitro, also when luzindole or 4-P-PDOT was present in a medium. On the other hand, melatonin at a concentration of 10-7 M diminished this neurohormone output from an isolated H-N system and into the blood. Luzindole significantly suppressed such melatonin action, while 4-P-PDOT did not change the inhibitory influence of 10-7 M melatonin on oxytocin release, both in vitro and in vivo. CONCLUSIONS: The present study demonstrates that an inhibitory effect of 10-7 M melatonin on oxytocin secretion from the rat H-N system is mediated through a subtype MT1 membrane receptor and its action is independent of subtype MT2 receptor. However, for the stimulatory effect of pharmacological concentration (10-3 M) of the pineal hormone on oxytocin release, probably mechanisms other than membrane MT1/MT2 receptor(s)-dependent are involved. (Endokrynol Pol 2016; 67 (5): 507-514). PMID- 26884305 TI - Is galectin-3 associated with urinary albumin excretion in type 2 diabetes? AB - INTRODUCTION: The relationship between galectin-3 and diabetes mellitus or renal function has recently been investigated. In this study, we tried to evaluate the association of galectin-3 in urinary albumin excretion levels in type 2 diabetic patients. MATERIAL AND METHODS: In a group of 137 type 2 diabetes patients, the mean of the last three urinary microalbumin/creatinine ratios and galectin-3 levels were evaluated. The patient group was divided into three subgroups according to their level of albuminuria calculated with urine microalbumin/creatinine ratio. RESULTS: There was no significant difference between the galectin values of the three subgroups. Significant differences were observed between GFR results of group 1 vs. 3 (p < 0.0001) and group 2 vs. 3 (p = 0.0006), and serum creatinine results of group 1 vs. 3 (p = 0.0003) and group 2 vs. 3 (p < 0.0001). The three subgroups did not reveal any significant difference concerning the age, BMI, duration of DM, FPG, and HbA1c levels. CONCLUSIONS: We concluded that serum galectin-3 values are not affected by the levels of urinary albumin excretion in DM patients. We could not find any relation between galectin 3 and the parameters of DM such as FPG, HbA1c, and duration of the disease. (Endokrynol Pol 2016; 67 (6): 580-584). PMID- 26884306 TI - ROHHAD in a 9-year-old boy - clinical case. AB - ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation) is characterized by rapid-onset obesity in young children, hypoventilation, and hypothalamic and autonomic dysfunction. The exact aetiology of the disease remains unknown, and the number of reported cases seems to be underestimated. We present the case of a nine-year old male patient suspected of ROHHAD due to weight gain since early childhood, decreased height velocity, hypoventilation, hypodipsia, excessive perspiration, and pyrexial episodes. The presented symptoms, and laboratory and imaging findings met the criteria of ROHHAD syndrome. ROHHAD should be considered in differential diagnosis for obesity in children. Early identification of the disease prevents potential complications specific for the syndrome, in particular a life-threatening cardio-pulmonary arrest. Patients with ROHHAD require regular follow-up by a multidisciplinary team. PMID- 26884307 TI - Late liver metastasis of medullary thyroid cancer with low calcitonin levels - successfully cured by radiofrequency. AB - A 28-year-old female consulted in 1994 for a left thyroid nodule known for two years with documented progression. Left lobe resection was performed initially followed by total thyroidectomy without lymph node dissection in September 1994. Pathological examination concluded on unilateral 10 * 40 mm medullary thyroid carcinoma (MTC). RET mutation was negative. Basal and pentagastrin-stimulated CT levels had been normal from 1994 to 2008 when her CT level was found to be elevated at 33 ng/L and increased subsequently to 111 ng/L in 2010. In accordance with guidelines, cervical ultrasound was performed repeatedly with negative results. After discussion in a multidisciplinary meeting and with patient's consent, an F-Dopa PET scan was proposed in disagreement with guidelines. This scan showed unique uptake in liver segment VI, which was confirmed by MRI. CT levels reached to 253 ng/L when she finally accepted treatment. In February 2013 we performed radiofrequency ablation of the lesion, which allowed normalisation of CT levels. This observation highlights the possibility of late recurrence of MTC. We could propose that for MTC patients with low-calcitonin levels recurrences F-DOPA-PET/CT is a good diagnostic tool to use in case of repeatedly negative US neck studies. (Endokrynol Pol 2016; 67 (3): 326-329). PMID- 26884308 TI - Diagnosis, treatment, and prognosis in patients with liver metastases from follicular thyroid carcinoma (FTC). AB - Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer (TC) and accounts for approximately 10% of all TC cases. Liver metastases are a rare presentation in 0.5-1% of follicular thyroid cancers, usually occurring in the setting of widely disseminated FTC disease, and their presence is associated with poor prognosis. Until now, there have been only 30 cases of FTC liver metastases described in the literature. Herein, we review publications and describe diagnostic tools that may be used in the diagnosis and follow-up of FTC metastases to the liver, including biopsy and imaging techniques like US, CT, MRI, SPECT, PET, and radioiodine scintigraphy. We also present and discuss current methods of treatment, e.g. TSH suppressive therapy with levothyroxine, surgery, radiofrequency ablation (RFA), transarterial embolisation (TAE), liver transarterial chemoembolisation (TACE), chemotherapy with cisplatin and doxorubicin, treatment with Indium- 111-octreotide (or its analogues), and tyrosine kinase inhibitors (sorafenib, sunitinib). At the end we describe the course, results of diagnostics, and treatment in a patient with large multiple FTC metastases to the liver. (Endokrynol Pol 2016; 67 (3): 332-347). PMID- 26884309 TI - Recent HIV Testing Among Young Men Who Have Sex with Men in Bangkok and Chiang Mai: HIV Testing and Prevention Strategies Must Be Enhanced in Thailand. AB - HIV infection among men who have sex with men, particularly in Thai urban settings and among younger cohorts, is escalating. HIV testing and counseling (HTC) are important for prevention and obtaining treatment and care. We examine data from a 2013 survey of males, 15-24 years, reporting past-year sex with a male and living in Bangkok or Chiang Mai. Almost three quarters of young MSM (YMSM) in Bangkok and only 27 % in Chiang Mai had an HIV test in the previous year. Associations for HIV testing varied between cities, although having employment increased the odds of HIV testing for both cities. In Bangkok, family knowledge of same sex attraction and talking to parents/guardians about HIV/AIDS had higher odds of HIV testing. Expanded HTC coverage is needed for YMSM in Chiang Mai. All health centers providing HTC, including those targeting MSM, need to address the specific needs of younger cohorts. PMID- 26884311 TI - Psychosocial Factors Associated with Resilience in a National Community-Based Cohort of Australian Gay Men Living with HIV. AB - HIV-positive gay men may experience multiple sources of adversity and stress, related both to their HIV diagnosis and sexual identity. Most of these men, however, do not experience mental health problems. Little is known about factors that help them achieve resilience in the face of life challenges. This study examined psychosocial factors associated with resilience in a national community based sample of 357 Australian HIV-positive gay men. Resilience was measured using the Connor-Davidson Resilience Scale. Higher levels of resilience were linked with experiencing low or no internalized HIV-related stigma, having no previous history of mental health problems, and a number of socioeconomic indicators. In addition to providing a more complete picture of the mental health of HIV-positive gay men, findings from this study can be used to inform strength based approaches to mental health prevention and support. PMID- 26884310 TI - Pre-exposure Prophylaxis Awareness Among Gay and Other Men who have Sex with Men in Vancouver, British Columbia, Canada. AB - Men who have sex with men (MSM) account for approximately half of Canada's new HIV infections. Pre-exposure prophylaxis (PrEP), a recently established and effective HIV prevention tool for MSM is currently not approved nor publicly funded. We recruited MSM via respondent-driven sampling to complete a self administered computer-based interview. Stratified by HIV status, multivariable logistic regression identified factors associated with PrEP awareness. Of 673 participants, 102/500 (20.9 %) HIV-negative and 63/173 (26.5 %) HIV-positive men were aware of PrEP, but none had used it. One third of PrEP-aware MSM spoke about it with friends or sex partners. Self-declared knowledge was limited. Factors associated with PrEP awareness varied by HIV status, but included greater HAART optimism for HIV-negative MSM. Among HIV-negative MSM, being PrEP unaware was associated with younger age, not always having condoms, and preferring receptive versus insertive anal sex. Future longitudinal research should identify early adopters of PrEP and its associated impacts. PMID- 26884313 TI - Roles of the ER-alpha36-EGFR/HER2 positive regulatory loops in tamoxifen resistance. AB - Tamoxifen provided a successful treatment for ER-positive breast cancer for the past four decades. However, most breast tumors are eventually resistant to tamoxifen therapy. Extensive researches were conducted to understand the molecular mechanisms involved in tamoxifen resistance, and have revealed that multiple signaling molecules and pathways such as EGFR and HER2 are involved in tamoxifen resistance. Currently, the mechanisms by which tamoxifen sensitive breast cancer cells acquire these signaling pathways and develop tamoxifen resistance have not been elucidated. The identification of ER-alpha36, a variant of ER-alpha, that is able to mediate agonist activity of tamoxifen provided great insights into the underlying mechanisms of tamoxifen resistance. In this review, we will discuss the biological function and the possible underlying mechanisms of ER-alpha36 in tamoxifen resistance and specifically illustrate a novel cross-talk mechanism; positive regulatory loops between the ER-alpha36 and EGFR/HER2 in tamoxifen resistance. The function and the underlying mechanisms of ER-alpha36 in tamoxifen resistance of the breast cancer stem/progenitor cells will also be discussed. Finally, we will postulate a novel approach to restore tamoxifen sensitivity in tamoxifen resistant breast cancer cells. PMID- 26884312 TI - MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors. AB - Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies. PMID- 26884314 TI - Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury. AB - T helper (Th) 17 cells and CD4(+) CD25(+) regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-beta and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL 35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID- 26884315 TI - Communication training improves patient-centered provider behavior and screening for soldiers' mental health concerns. AB - OBJECTIVE: To evaluate the effectiveness of patient-centered communication training for military providers who conduct post-deployment health screening. The half-day interactive workshop included simulated Soldier patients using video technology. METHODS: Using a quasi-experimental design, all health care providers at four military treatment facilities were recruited for data collection during a four- to nine-day site visit (23 trained providers, 28 providers in the control group, and one provider declined to participate). All Soldiers were eligible to participate and were blinded to provider training status. Immediately after screening encounters, providers reported on their identification of mental health concerns and Soldiers reported on provider communication behaviors resulting in 1,400 matched pairs. Electronic health records were also available for 26,005 Soldiers. RESULTS: The workshop was found to increase (1) providers' patient centered communication behaviors as evaluated by Soldiers; (2) provider identification of Soldier mental health concerns; and (3), related health outcomes including provision of education and referral to a confidential counseling resource. CONCLUSION: Results are promising, but with small effect sizes and study limitations, further research is warranted. PRACTICE IMPLICATIONS: A brief intensive workshop on patient-centered communication tailored to the military screening context is feasible and may improve key outcomes. PMID- 26884317 TI - An open letter to The BMJ editors on qualitative research. PMID- 26884316 TI - Combination Protocol of Low-Frequency rTMS and Intensive Occupational Therapy for Post-stroke Upper Limb Hemiparesis: a 6-year Experience of More Than 1700 Japanese Patients. AB - Several years ago, we proposed a combination protocol of repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) for upper limb hemiparesis after stroke. Subsequently, the number of patients treated with the protocol has increased in Japan. We aimed to present the latest data on our proposed combination protocol for post-stroke upper limb hemiparesis as a result of a multi-institutional study. After confirming that a patient met the inclusion criteria for the protocol, they were scheduled to receive the 15-day inpatient protocol. In the protocol, two sessions of 20-min rTMS and 120-min occupational therapy were provided daily, except for Sundays and the days of admission/discharge. Motor function of the affected upper limb was evaluated by the Fugl-Meyer assessment (FMA) and Wolf motor function test (WMFT) at admission/discharge and at 4 weeks after discharge if possible. A total of 1725 post-stroke patients were studied (mean age at admission 61.4 +/- 13.0 years). The scheduled 15-day protocol was completed by all patients. At discharge, the increase in FMA score, shortening in performance time of WMFT, and increase in functional ability scale (FAS) score of WMFT were significant (FMA score 46.8 +/- 12.2 to 50.9 +/- 11.4 points, p < 0.001; performance time of WMFT 2.57 +/- 1.32 to 2.21 +/- 1.33, p < 0.001; FAS score of WMFT 47.4 +/- 14. to 51.4 +/- 14.3 points, p < 0.001). Our proposed combination protocol can be a potentially safe and useful therapeutic intervention for upper limb hemiparesis after stroke, although its efficacy should be confirmed in a randomized controlled study. PMID- 26884318 TI - Substrate-Sensitive Graphene Oxidation. AB - The inertness of graphene toward reaction with ambient molecules is essential for realizing durable devices with stable performance. Many device applications require graphene to contact with substrates, but whose impact on the chemical property of graphene has been largely overlooked. Here, we combine comprehensive first-principles analyses with experiments to show that graphene oxidation is highly sensitive to substrates. Graphene remains inert on SiO2 and hexagonal boron nitride but becomes increasingly weak against oxidation on metal substrates because of enhanced charge transfer and chemical interaction between them. In particular, Ni and Co substrates lead to spontaneous oxidation of graphene, while a Cu substrate maximally promotes the oxygen diffusion on graphene, with an estimated diffusivity 13 orders of magnitude higher than that on freestanding graphene. Bilayer graphene is revealed to have high oxidation resistance independent of substrate and thus is a better choice for high-performance nanoelectronics. Our findings should be extendable to a wide spectrum of chemical functionalizations of two-dimensional materials mediated by substrates. PMID- 26884319 TI - Dose- and time-dependent effects of actomyosin inhibition on live mouse outflow resistance and aqueous drainage tissues. AB - Actomyosin contractility modulates outflow resistance of the aqueous drainage tissues and intraocular pressure, a key pathogenic factor of glaucoma. We established methodology to reliably analyze the effect of latrunculin-B (Lat-B) induced actin depolymerization on outflow physiology in live mice. A voltage controlled microperfusion system for delivering drugs and simultaneously analyzing outflow resistance was tested in live C57BL/6 mice. Flow rate and perfusion pressure were reproducible within a coefficient of variation of 2%. Outflow facility for phosphate-buffered saline (0.0027 +/- 0.00036 MUL/min/mmHg; mean +/- SD) and 0.02% ethanol perfusions (Lat-B vehicle; 0.0023 +/- 0.0005 MUL/min/mmHg) were similar and stable over 2 hours (p > 0.1 for change), indicating absence of a 'washout' artifact seen in larger mammals. Outflow resistance changed in graded fashion, decreasing dose- and time-dependently over 2 hours for Lat-B doses of 2.5 MUM (p = 0.29), 5 MUM (p = 0.039) and 10 MUM (p = 0.001). Resulting outflow resistance was about 10 times lower with 10 MUM Lat-B than vehicle control. The filamentous actin network was decreased and structurally altered in the ciliary muscle (46 +/- 5.6%) and trabecular meshwork (37 +/- 8.3%) of treated eyes relative to vehicle controls (p < 0.005; 5 MUM Lat B). Mouse actomyosin contractile mechanisms are important to modulating aqueous outflow resistance, mirroring mechanisms in primates. We describe approaches to reliably probe these mechanisms in vivo. PMID- 26884320 TI - Hospital re-admission associated with adverse drug reactions in patients over the age of 65 years. AB - CONTEXT: Adverse drug reactions (ADRs) are responsible for 5 % of hospital admissions, but hospital re-admission induced by ADRs remains poorly documented. OBJECTIVE: The aim of this study was to estimate the rate of hospital re admission and the factors associated with re-admission in the patients over the age of 65 years. Secondary, we described the characteristics of cases of ADRs leading to re-admission for drugs other than chemotherapy agents. METHODS: Data were extracted from hospital discharge summaries provided by the Department of Medical Information of Toulouse University Hospital. All patients over the age of 65 years admitted to the hospital in 2010 for an ADR, identified from ICD-10 codes, were selected. All subsequent admissions of members of this cohort within 1 year of discharge following the index admission were reviewed retrospectively. The risk factors associated with hospital re-admission for ADRs were analyzed. Medical records were used for descriptive analysis of re-admission due to drugs other than chemotherapy agents. RESULTS: We found that 553 of the 1000 patients admitted for ADRs in 2010 were re-admitted to hospital within 1 year. Among them, 87 cases were re-admitted for ADRs (estimated rate of 87/1000 re-admission for an ADR within 1 year). A comparison of the patients re-admitted for ADRs (n = 87) with those of patients re-admitted for other causes (n = 410) suggested that only cancer increased the risk of re-admission for ADRs (OR = 7.69 [4.59-12.88] 95 % CI). ADRs due to the same drug combination were the suspected cause of repeat admission in half the cases (other than chemotherapy). Hospital re-admission was considered avoidable in four cases (22 %). CONCLUSION: This study shows an estimated rate of re-admission for an ADR around 87/1000 within 1 year, and the same drug combination were the suspected cause of repeat admission in half the cases. At least, 11 % of cases were avoidable. PMID- 26884321 TI - Poly(vinyl benzyl trimethylammonium chloride) Homo and Block Copolymers Complexation with DNA. AB - In this work we focus on the use of novel homo and block copolymers based on poly(vinyl benzyl trimethylammonium chloride) as gene delivery vectors. The homopolymers and block copolymers were synthesized by RAFT polymerization schemes and molecularly characterized. DNA/polymer complexes (polyplexes) in a wide range of N/P (amino-to-phosphate groups) ratios were prepared. The ability of the novel polymers to form complexes with linear DNA was investigated by light scattering, zeta potential, and ethidium bromide fluorescence quenching measurements. The resulting polyplexes were in the size range of 80-300 nm and their surface potential changed from negative to positive depending on the N/P ratio. The stability of polyplexes was monitored by changes in their hydrodynamic parameters in the presence of salt. The novel vector systems were visualized by transmission electron microscopy. The influence of factors such as molar mass, content, and chemical structure of the polycationic moieties as well as presence of a hydrophilic poly[oligo(ethylene glycol) methacrylate] block on the structure and stability of the polyplexes, kinetics of their formation, and effectiveness of the (co)polymers to shrink and pack DNA was discussed. PMID- 26884323 TI - Systematic microRNAome profiling reveals the roles of microRNAs in milk protein metabolism and quality: insights on low-quality forage utilization. AB - In this study, we investigated the molecular regulatory mechanisms of milk protein production in dairy cows by studying the miRNAomes of five key metabolic tissues involved in protein synthesis and metabolism from dairy cows fed high- and low-quality diets. In total, 340, 338, 337, 330, and 328 miRNAs were expressed in the rumen, duodenum, jejunum, liver, and mammary gland tissues, respectively. Some miRNAs were highly correlated with feed and nitrogen efficiency, with target genes involved in transportation and phosphorylation of amino acid (AA). Additionally, low-quality forage diets (corn stover and rice straw) influenced the expression of feed and nitrogen efficiency-associated miRNAs such as miR-99b in rumen, miR-2336 in duodenum, miR-652 in jejunum, miR-1 in liver, and miR-181a in mammary gland. Ruminal miR-21-3p and liver miR-2285f were predicted to regulate AA transportation by targeting ATP1A2 and SLC7A8, respectively. Furthermore, bovine-specific miRNAs regulated the proliferation and morphology of rumen epithelium, as well as the metabolism of liver lipids and branched-chain AAs, revealing bovine-specific mechanisms. Our results suggest that miRNAs expressed in these five tissues play roles in regulating transportation of AA for downstream milk production, which is an important mechanism that may be associated with low milk protein under low-quality forage feed. PMID- 26884324 TI - Authors' Reply to Montastruc et al.: "Drug-Induced Hyperglycaemia and Diabetes". PMID- 26884322 TI - Endocytic recycling protein EHD1 regulates primary cilia morphogenesis and SHH signaling during neural tube development. AB - Members of the four-member C-terminal EPS15-Homology Domain-containing (EHD) protein family play crucial roles in endocytic recycling of cell surface receptors from endosomes to the plasma membrane. In this study, we show that Ehd1 gene knockout in mice on a predominantly B6 background is embryonic lethal. Ehd1 null embryos die at mid-gestation with a failure to complete key developmental processes including neural tube closure, axial turning and patterning of the neural tube. We found that Ehd1-null embryos display short and stubby cilia on the developing neuroepithelium at embryonic day 9.5 (E9.5). Loss of EHD1 also deregulates the ciliary SHH signaling with Ehd1-null embryos displaying features indicative of increased SHH signaling, including a significant downregulation in the formation of the GLI3 repressor and increase in the ventral neuronal markers specified by SHH. Using Ehd1-null MEFS we found that EHD1 protein co-localizes with the SHH receptor Smoothened in the primary cilia upon ligand stimulation. Under the same conditions, EHD1 was shown to co-traffic with Smoothened into the developing primary cilia and we identify EHD1 as a direct binding partner of Smoothened. Overall, our studies identify the endocytic recycling regulator EHD1 as a novel regulator of the primary cilium-associated trafficking of Smoothened and Hedgehog signaling. PMID- 26884325 TI - Comment on: "Drug-Induced Hyperglycaemia and Diabetes". PMID- 26884326 TI - The Safety of Prochlorperazine in Children: A Systematic Review and Meta Analysis. AB - INTRODUCTION: Prochlorperazine is recommended for adults with breakthrough or refractory chemotherapy-induced nausea and vomiting (CINV). The objective of this review was to describe its safety in children when given for any indication to help define its role for CINV control in children. METHODS: Electronic searches of MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials were performed as of 9 March 2015. All studies in English reporting adverse effects (AEs) associated with prochlorperazine in children (<=18 years) were included. AEs were synthesized for prospective studies. RESULTS: Forty-nine (15 prospective) studies evaluating the use of prochlorperazine in 758 children were included. The most commonly reported AEs in prospective studies of prochlorperazine in children were sedation (multiple-dose studies: 10 %, 95 % CI 5-21) and extrapyramidal symptoms (EPS) (single-dose studies: 9 %, 95 % CI 3-29; multiple-dose studies: 4 %, 95 % CI 1-11). Serious AEs (seizure, neuroleptic malignant syndrome, autonomic collapse, tardive dyskinesia) were rarely associated with prochlorperazine use in children. Five fatalities were reported in children receiving prochlorperazine. LIMITATIONS: The limitations of this systematic review and meta-analysis were that the AEs reported in the included studies were heterogeneous, the prospective use of systematic clinical tools to identify AEs was rare, and the risk of bias in most prospective studies was moderate. CONCLUSIONS: The most common AEs reported with the pediatric use of prochlorperazine are EPS and sedation. Fatalities, life-threatening, and persistent AEs have also been reported. PMID- 26884328 TI - Percutaneous Management of Accidentally Retained Foreign Bodies During Image Guided Non-vascular Procedures: Novel Technique Using a Large-Bore Biopsy System. AB - OBJECTIVE: To describe a novel percutaneous image-guided technique using a large bore biopsy system to retrieve foreign bodies (FBs) accidentally retained during non-vascular interventional procedures. MATERIALS AND METHODS: Between May 2013 and October 2015, five patients underwent percutaneous retrieval of five iatrogenic FBs, including a biopsy needle tip in the femoral head following osteoblastoma biopsy and radiofrequency ablation (RFA); a co-axial needle shaft within a giant desmoid tumour following cryoablation; and three post vertebroplasty cement tails within paraspinal muscles. All FBs were retrieved immediately following original procedures under local or general anaesthesia, using combined computed tomography (CT) and fluoroscopic guidance. The basic technique involved positioning a 6G trocar sleeve around the FB long axis and co axially advancing an 8G biopsy needle to retrieve the FB within the biopsy core. Retrospective chart review facilitated analysis of procedures, FBs, technical success, and complications. RESULTS: Mean FB size was 23 mm (range 8-74 mm). Four FBs were located within 10 mm of non-vascular significant anatomic structures. The basic technique was successful in 3 cases; 2 cases required technical modifications including using a stiff guide-wire to facilitate retrieval in the case of the post-cryoablation FB; and using the central mandrin of the 6G trocar to push a cement tract back into an augmented vertebra when initial retrieval failed. Overall technical success (FB retrieval or removal to non-hazardous location) was 100 %, with no complications. CONCLUSION: Percutaneous image-guided retrieval of iatrogenic FBs using a large-bore biopsy system is a feasible, safe, effective, and versatile technique, with potential advantages over existing methods. PMID- 26884329 TI - The Role of Embryonic Stem Cell-expressed RAS (ERAS) in the Maintenance of Quiescent Hepatic Stellate Cells. AB - Hepatic stellate cells (HSCs) were recently identified as liver-resident mesenchymal stem cells. HSCs are activated after liver injury and involved in pivotal processes, such as liver development, immunoregulation, regeneration, and also fibrogenesis. To date, several studies have reported candidate pathways that regulate the plasticity of HSCs during physiological and pathophysiological processes. Here we analyzed the expression changes and activity of the RAS family GTPases and thereby investigated the signaling networks of quiescent HSCs versus activated HSCs. For the first time, we report that embryonic stem cell-expressed RAS (ERAS) is specifically expressed in quiescent HSCs and down-regulated during HSC activation via promoter DNA methylation. Notably, in quiescent HSCs, the high level of ERAS protein correlates with the activation of AKT, STAT3, mTORC2, and HIPPO signaling pathways and inactivation of FOXO1 and YAP. Our data strongly indicate that in quiescent HSCs, ERAS targets AKT via two distinct pathways driven by PI3Kalpha/delta and mTORC2, whereas in activated HSCs, RAS signaling shifts to RAF-MEK-ERK. Thus, in contrast to the reported role of ERAS in tumor cells associated with cell proliferation, our findings indicate that ERAS is important to maintain quiescence in HSCs. PMID- 26884330 TI - Manipulation of Interleukin-1beta and Interleukin-18 Production by Yersinia pestis Effectors YopJ and YopM and Redundant Impact on Virulence. AB - Innate immunity plays a central role in resolving infections by pathogens. Host survival during plague, caused by the Gram-negative bacterium Yersinia pestis, is favored by a robust early innate immune response initiated by IL-1beta and IL-18. These cytokines are produced by a two-step mechanism involving NF-kappaB-mediated pro-cytokine production and inflammasome-driven maturation into bioactive inflammatory mediators. Because of the anti-microbial effects induced by IL 1beta/IL-18, it may be desirable for pathogens to manipulate their production. Y. pestis type III secretion system effectors YopJ and YopM can interfere with different parts of this process. Both effectors have been reported to influence inflammasome caspase-1 activity; YopJ promotes caspase-8-dependent cell death and caspase-1 cleavage, whereas YopM inhibits caspase-1 activity via an incompletely understood mechanism. However, neither effector appears essential for full virulence in vivo Here we report that the sum of influences by YopJ and YopM on IL-1beta/IL-18 release is suppressive. In the absence of YopM, YopJ minimally affects caspase-1 cleavage but suppresses IL-1beta, IL-18, and other cytokines and chemokines. Importantly, we find that Y. pestis containing combined deletions of YopJ and YopM induces elevated levels of IL-1beta/IL-18 in vitro and in vivo and is significantly attenuated in a mouse model of bubonic plague. The reduced virulence of the YopJ-YopM mutant is dependent on the presence of IL-1beta, IL 18, and caspase-1. Thus, we conclude that Y. pestis YopJ and YopM can both exert a tight control of host IL-1beta/IL-18 production to benefit the bacteria, resulting in a redundant impact on virulence. PMID- 26884331 TI - Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea. AB - Tissue regeneration is a complex process that involves a mosaic of molecules that vary spatially and temporally. Insights into the chemical signaling underlying this process can be achieved with a multiplex and untargeted chemical imaging method such as mass spectrometry imaging (MSI), which can enablede novostudies of nervous system regeneration. A combination of MSI and multivariate statistics was used to differentiate peptide dynamics in the freshwater planarian flatwormSchmidtea mediterraneaat different time points during cephalic ganglia regeneration. A protocol was developed to makeS. mediterraneatissues amenable for MSI. MS ion images of planarian tissue sections allow changes in peptides and unknown compounds to be followed as a function of cephalic ganglia regeneration. In conjunction with fluorescence imaging, our results suggest that even though the cephalic ganglia structure is visible after 6 days of regeneration, the original chemical composition of these regenerated structures is regained only after 12 days. Differences were observed in many peptides, such as those derived from secreted peptide 4 and EYE53-1. Peptidomic analysis further identified multiple peptides from various known prohormones, histone proteins, and DNA- and RNA-binding proteins as being associated with the regeneration process. Mass spectrometry data also facilitated the identification of a new prohormone, which we have named secreted peptide prohormone 20 (SPP-20), and is up-regulated during regeneration in planarians. PMID- 26884332 TI - DNA and Protein Requirements for Substrate Conformational Changes Necessary for Human Flap Endonuclease-1-catalyzed Reaction. AB - Human flap endonuclease-1 (hFEN1) catalyzes the essential removal of single stranded flaps arising at DNA junctions during replication and repair processes. hFEN1 biological function must be precisely controlled, and consequently, the protein relies on a combination of protein and substrate conformational changes as a prerequisite for reaction. These include substrate bending at the duplex duplex junction and transfer of unpaired reacting duplex end into the active site. When present, 5'-flaps are thought to thread under the helical cap, limiting reaction to flaps with free 5'-terminiin vivo Here we monitored DNA bending by FRET and DNA unpairing using 2-aminopurine exciton pair CD to determine the DNA and protein requirements for these substrate conformational changes. Binding of DNA to hFEN1 in a bent conformation occurred independently of 5'-flap accommodation and did not require active site metal ions or the presence of conserved active site residues. More stringent requirements exist for transfer of the substrate to the active site. Placement of the scissile phosphate diester in the active site required the presence of divalent metal ions, a free 5'-flap (if present), a Watson-Crick base pair at the terminus of the reacting duplex, and the intact secondary structure of the enzyme helical cap. Optimal positioning of the scissile phosphate additionally required active site conserved residues Tyr(40), Asp(181), and Arg(100)and a reacting duplex 5'-phosphate. These studies suggest a FEN1 reaction mechanism where junctions are bound and 5'-flaps are threaded (when present), and finally the substrate is transferred onto active site metals initiating cleavage. PMID- 26884333 TI - Identification of a Substrate Recognition Domain in the Replication Stress Response Protein Zinc Finger Ran-binding Domain-containing Protein 3 (ZRANB3). AB - DNA damage and other forms of replication stress can cause replication forks to stall. Replication stress response proteins stabilize and resolve stalled forks by mechanisms that include fork remodeling to facilitate repair or bypass of damaged templates. Several enzymes including SMARCAL1, HLTF, and ZRANB3 catalyze these reactions. SMARCAL1 and HLTF utilize structurally distinct accessory domains attached to an ATPase motor domain to facilitate DNA binding and catalysis of fork remodeling reactions. Here we describe a substrate recognition domain within ZRANB3 that is needed for it to recognize forked DNA structures, hydrolyze ATP, catalyze fork remodeling, and act as a structure-specific endonuclease. Thus, substrate recognition domains are a common feature of fork remodeling, SNF2-family, DNA-dependent ATPases, and our study provides further mechanistic understanding of how these enzymes maintain genome integrity during DNA replication. PMID- 26884334 TI - Intramolecular Interactions and Regulation of Cofactor Binding by the Four Repressive Elements in the Caspase Recruitment Domain-containing Protein 11 (CARD11) Inhibitory Domain. AB - The CARD11 signaling scaffold transmits signaling between antigen receptors on B and T lymphocytes and the transcription factor NF-kappaB during the adaptive immune response. CARD11 activity is controlled by an inhibitory domain (ID), which participates in intramolecular interactions and prevents cofactor binding prior to receptor triggering. Oncogenic CARD11 mutations associated with the activated B cell-like subtype of diffuse large B cell lymphoma somehow perturb ID mediated autoinhibition to confer CARD11 with the dysregulated spontaneous signaling to NF-kappaB that is required for the proliferation and survival of the lymphoma. Here, we investigate how the four repressive elements (REs) we have discovered in the CARD11 ID function to inhibit CARD11 activity with cooperativity and redundancy. We find that each RE contributes to the maintenance of the closed inactive state of CARD11 that predominates in the absence of receptor engagement. Each RE also contributes to the prevention of Bcl10 binding in the basal unstimulated state. RE1, RE2, and RE3 participate in intramolecular interactions with other CARD11 domains and share domain targets for binding. Remarkably, diffuse large B cell lymphoma-associated gain-of-function mutations in the caspase recruitment domain, LATCH, or coiled coil can perturb intramolecular interactions mediated by multiple REs, suggesting how single amino acid oncogenic CARD11 mutations can perturb or bypass the action of redundant inhibitory REs to achieve the level of hyperactive CARD11 signaling required to support lymphoma growth. PMID- 26884335 TI - Cooperative Control of Caspase Recruitment Domain-containing Protein 11 (CARD11) Signaling by an Unusual Array of Redundant Repressive Elements. AB - Several classes of signaling proteins contain autoinhibitory domains that prevent unwarranted signaling and coordinate the induction of activity in response to external cues. CARD11, a scaffold protein critical for antigen receptor signaling to NF-kappaB, undergoes autoregulation by a poorly understood inhibitory domain (ID), which keeps CARD11 inactive in the absence of receptor triggering through inhibitory intramolecular interactions. This autoinhibitory strategy makes CARD11 highly susceptible to gain-of-function mutations that are frequently observed in diffuse large B cell lymphoma (DLBCL) and that disrupt ID-mediated autoinhibition, leading to constitutive NF-kappaB activity, which can promote lymphoma proliferation. Although DLBCL-associated CARD11 mutations in the caspase recruitment domain (CARD), LATCH domain, and coiled coil have been shown to disrupt intramolecular ID binding, surprisingly, no gain-of-function mutations in the ID itself have been reported and validated. In this study, we solve this paradox and report that the CARD11 ID contains an unusual array of four repressive elements that function cooperatively with redundancy to prevent spontaneous NF-kappaB activation. Our quantitative analysis suggests that potent oncogenic CARD11 mutations must perturb autoinhibition by at least three repressive elements. Our results explain the lack of ID mutations in DLBCL and reveal an unusual autoinhibitory domain structure and strategy for preventing unwarranted scaffold signaling to NF-kappaB. PMID- 26884336 TI - Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases. AB - The cysteine protease cathepsin C (CatC) activates granule-associated proinflammatory serine proteases in hematopoietic precursor cells. Its early inhibition in the bone marrow is regarded as a new therapeutic strategy for treating proteolysis-driven chronic inflammatory diseases, but its complete inhibition is elusive in vivo Controlling the activity of CatC may be achieved by directly inhibiting its activity with a specific inhibitor or/and by preventing its maturation. We have investigated immunochemically and kinetically the occurrence of CatC and its proform in human hematopoietic precursor cells and in differentiated mature immune cells in lung secretions. The maturation of proCatC obeys a multistep mechanism that can be entirely managed by CatS in neutrophilic precursor cells. CatS inhibition by a cell-permeable inhibitor abrogated the release of the heavy and light chains from proCatC and blocked ~80% of CatC activity. Under these conditions the activity of neutrophil serine proteases, however, was not abolished in precursor cell cultures. In patients with neutrophilic lung inflammation, mature CatC is found in large amounts in sputa. It is secreted by activated neutrophils as confirmed through lipopolysaccharide administration in a nonhuman primate model. CatS inhibitors currently in clinical trials are expected to decrease the activity of neutrophilic CatC without affecting those of elastase-like serine proteases. PMID- 26884338 TI - Identification of an Extracellular Gate for the Proton-coupled Folate Transporter (PCFT-SLC46A1) by Cysteine Cross-linking. AB - The proton-coupled folate transporter (PCFT, SLC46A1) is required for intestinal folate absorption and folate homeostasis in humans. A homology model of PCFT, based upon theEscherichia coliglycerol 3-phosphate transporter structure, predicted that PCFT transmembrane domains (TMDs) 1, 2, 7, and 11 form an extracellular gate in the inward-open conformation. To assess this model, five residues (Gln(45)-TMD1, Asn(90)-TMD2, Leu(290)-TMD7, Ser(407)-TMD11 and Asn(411) TMD11) in the predicted gate were substituted with Cys to generate single and nine double mutants. Transport function of the mutants was assayed in transient transfectants by measurement of [(3)H]substrate influx as was accessibility of the Cys residues to biotinylation. Pairs of Cys residues were assessed for spontaneous formation of a disulfide bond, induction of a disulfide bond by oxidization with dichloro(1,10-phenanthroline)copper (II) (CuPh), or the formation of a Cd(2+)complex. The data were consistent with the formation of a spontaneous disulfide bond between the N90C/S407C pair and a CuPh- and Cd(2+) induced disulfide bond and complex, respectively, for the Q45C/L290C and L290C/N411C pairs. The decrease in activity induced by cross-linkage of the Cys residue pairs was due to a decrease in the influxVmaxconsistent with restriction in the mobility of the transporter. The presence of folate substrate decreased the CuPh-induced inhibition of transport. Hence, the data support the glycerol 3 phosphate transporter-based homology model of PCFT and the presence of an extracellular gate formed by TMDs 1, 2, 7, and 11. PMID- 26884337 TI - Subunit-selective N-Methyl-d-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation. AB - The maturation of glutamatergic synapses in the CNS is regulated by NMDA receptors (NMDARs) that gradually change from a GluN2B- to a GluN2A-dominated subunit composition during postnatal development. Here we show that NMDARs control the activity of the small GTPase ADP-ribosylation factor 6 (Arf6) by consecutively recruiting two related brefeldin A-resistant Arf guanine nucleotide exchange factors, BRAG1 and BRAG2, in a GluN2 subunit-dependent manner. In young cortical cultures, GluN2B and BRAG1 tonically activated Arf6. In mature cultures, Arf6 was activated through GluN2A and BRAG2 upon NMDA treatment, whereas the tonic Arf6 activation was not detectable any longer. This shift in Arf6 regulation and the associated drop in Arf6 activity were reversed by a knockdown of BRAG2. Given their sequential recruitment during development, we examined whether BRAG1 and BRAG2 influence synaptic currents in hippocampal CA1 pyramidal neurons using patch clamp recordings in acute slices from mice at different ages. The number of AMPA receptor (AMPAR) miniature events was reduced by depletion of BRAG1 but not by depletion of BRAG2 during the first 2 weeks after birth. In contrast, depletion of BRAG2 during postnatal weeks 4 and 5 reduced the number of AMPAR miniature events and compromised the quantal sizes of both AMPAR and NMDAR currents evoked at Schaffer collateral synapses. We conclude that both Arf6 activation through GluN2B-BRAG1 during early development and the transition from BRAG1- to BRAG2-dependent Arf6 signaling induced by the GluN2 subunit switch are critical for the development of mature glutamatergic synapses. PMID- 26884339 TI - Clusterin Binds to Abeta1-42 Oligomers with High Affinity and Interferes with Peptide Aggregation by Inhibiting Primary and Secondary Nucleation. AB - The aggregation of amyloid beta protein (Abeta) is a fundamental pathogenic mechanism leading to the neuronal damage present in Alzheimer disease, and soluble Abeta oligomers are thought to be a major toxic culprit. Thus, better knowledge and specific targeting of the pathways that lead to these noxious species may result in valuable therapeutic strategies. We characterized some effects of the molecular chaperone clusterin, providing new and more detailed evidence of its potential neuroprotective effects. Using a classical thioflavin T assay, we observed a dose-dependent inhibition of the aggregation process. The global analysis of time courses under different conditions demonstrated that clusterin has no effect on the elongation rate but mainly interferes with the nucleation processes (both primary and secondary), reducing the number of nuclei available for further fibril growth. Then, using a recently developed immunoassay based on surface plasmon resonance, we obtained direct evidence of a high affinity (KD= 1 nm) interaction of clusterin with biologically relevant Abeta1 42oligomers, selectively captured on the sensor chip. Moreover, with the same technology, we observed that substoichiometric concentrations of clusterin prevent oligomer interaction with the antibody 4G8, suggesting that the chaperone shields hydrophobic residues exposed on the oligomeric assemblies. Finally, we found that preincubation with clusterin antagonizes the toxic effects of Abeta1 42oligomers, as evaluated in a recently developedin vivomodel inCaenorhabditis elegans.These data substantiate the interaction of clusterin with biologically active regions exposed on nuclei/oligomers of Abeta1-42, providing a molecular basis for the neuroprotective effects of the chaperone. PMID- 26884340 TI - Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch. AB - High tidal volume mechanical ventilation and the resultant excessive mechanical forces experienced by lung vascular endothelium are known to lead to increased vascular endothelial leak, but the underlying molecular mechanisms remain incompletely understood. One reported mechanotransduction pathway of increased endothelial cell (EC) permeability caused by high magnitude cyclic stretch (18% CS) involves CS-induced activation of the focal adhesion associated signalosome, which triggers Rho GTPase signaling. This study identified an alternative pathway of CS-induced EC permeability. We show here that high magnitude cyclic stretch (18% CS) rapidly activates VEGF receptor 2 (VEGFR2) signaling by dissociating VEGFR2 from VE-cadherin at the cell junctions. This results in VEGFR2 activation, Src-dependent VE-cadherin tyrosine phosphorylation, and internalization leading to increased endothelial permeability. This process is also accompanied by CS induced phosphorylation and internalization of PECAM1. Importantly, CS-induced endothelial barrier disruption was attenuated by VEGFR2 inhibition. 18% CS induced EC permeability was linked to dissociation of cell junction scaffold afadin from the adherens junctions. Forced expression of recombinant afadin in pulmonary endothelium attenuated CS-induced VEGFR2 and VE-cadherin phosphorylation, preserved adherens junction integrity and VEGFR2.VE-cadherin complex, and suppressed CS-induced EC permeability. This study shows for the first time a mechanism whereby VEGFR2 activation mediates EC permeability induced by pathologically relevant cyclic stretch. In this mechanism, CS induces dissociation of the VE-cadherin.VEGFR2 complex localized at the adherens juctions, causing activation of VEGFR2, VEGFR2-mediated Src-dependent phosphorylation of VE-cadherin, disassembly of adherens junctions, and EC barrier failure. PMID- 26884341 TI - Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate. AB - Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor component of total plasma membrane lipids, but it has a substantial role in the regulation of many cellular functions, including exo- and endocytosis. Recently, it was shown that PI(4,5)P2and syntaxin 1, a SNARE protein that catalyzes regulated exocytosis, form domains in the plasma membrane that constitute recognition sites for vesicle docking. Also, calcium was shown to promote syntaxin 1 clustering in the plasma membrane, but the molecular mechanism was unknown. Here, using a combination of superresolution stimulated emission depletion microscopy, FRET, and atomic force microscopy, we show that Ca(2+)acts as a charge bridge that specifically and reversibly connects multiple syntaxin 1/PI(4,5)P2complexes into larger mesoscale domains. This transient reorganization of the plasma membrane by physiological Ca(2+)concentrations is likely to be important for Ca(2+)-regulated secretion. PMID- 26884342 TI - Sequence Requirements for Neuropilin-2 Recognition by ST8SiaIV and Polysialylation of Its O-Glycans. AB - Polysialic acid is an oncofetal glycopolymer, added to the glycans of a small group of substrates, that controls cell adhesion and signaling. One of these substrates, neuropilin-2, is a VEGF and semaphorin co-receptor that is polysialylated on its O-glycans in mature dendritic cells and macrophages by the polysialyltransferase ST8SiaIV. To understand the biochemical basis of neuropilin 2 polysialylation, we created a series of domain swap chimeras with sequences from neuropilin-1, a protein for which polysialylation had not been previously reported. To our surprise, we found that membrane-associated neuropilin-1 is polysialylated at ~50% of the level of neuropilin-2 but not polysialylated when it lacks its cytoplasmic tail and transmembrane region and is secreted from the cell. This was not the case for neuropilin-2, which is polysialylated when either membrane-associated or soluble. Evaluation of the soluble chimeric proteins demonstrated that the meprin A5 antigen-MU tyrosine phosphatase (MAM) domain and the O-glycan-containing linker region of neuropilin-2 are necessary and sufficient for its polysialylation and serve as better recognition and acceptor sites in the polysialylation process than those regions of neuropilin-1. In addition, specific acidic residues on the surface of the MAM domain are critical for neuropilin-2 polysialylation. Based on these data and pull-down experiments, we propose a model where ST8SiaIV recognizes and docks on an acidic surface of the neuropilin-2 MAM domain to polysialylate O-glycans on the adjacent linker region. These results together with those related to neural cell adhesion molecule polysialylation establish a paradigm for the process of protein-specific polysialylation. PMID- 26884343 TI - Relationship between socioeconomic status and accessibility for endoscopic resection among gastric cancer patients: using National Health Insurance Cohort in Korea: poverty and endoscopic resection. AB - BACKGROUND: Gastric cancer is one of the most common types of cancer among patients in Korea. We measured the inequity in accessibility to endoscopic mucosal/submucosal resection (EMR) for early and curable gastric cancer treatment among different income classes in patients diagnosed from late 2011 to 2013. METHODS: Data were obtained from the National Health Insurance Cooperation Claim Data from patients diagnosed from late 2011 until the end of 2013, to provide a total of 1,671 patients with newly diagnosed carcinoma in situ of gastric and gastric cancer among 1,025,340 enrollees. Multiple logistic regression analysis was conducted to investigate the associations between independent variables and the rate of treatment with EMR. RESULTS: Among 1671 gastric cancer patients, 317 (19.0 %) subjects were treated with EMR. The 'lowest' income group was associated with a statistically significant lower rate of EMR treatment [odds ratio (OR) = 0.55, 95 % confidence index (CI) 0.34-0.89] compared to the 'highest' income group. The ORs for the 'low-middle' and 'middle-high' income groups were both higher than for the reference group, although these were not significantly different. According to the subgroup analysis by gender, rate of EMR treatment of 'lowest' income group (OR = 0.37, 95 % CI 0.18-0.74) was significantly lower only among men. CONCLUSION: In conclusion, we suggest that although universal health insurance in Korea has covered EMR treatment since August 2011, patients from the lowest income group are less likely to receive this treatment. Thus, we need to detect more eligible early-stage gastric cancer and treatment for individuals of low socioeconomic status. PMID- 26884345 TI - PNA lectin for purifying mouse acinar cells from the inflamed pancreas. AB - Better methods for purifying human or mouse acinar cells without the need for genetic modification are needed. Such techniques would be advantageous for the specific study of certain mechanisms, such as acinar-to-beta-cell reprogramming and pancreatitis. Ulex Europaeus Agglutinin I (UEA-I) lectin has been used to label and isolate acinar cells from the pancreas. However, the purity of the UEA I-positive cell fraction has not been fully evaluated. Here, we screened 20 widely used lectins for their binding specificity for major pancreatic cell types, and found that UEA-I and Peanut agglutinin (PNA) have a specific affinity for acinar cells in the mouse pancreas, with minimal affinity for other major pancreatic cell types including endocrine cells, duct cells and endothelial cells. Moreover, PNA-purified acinar cells were less contaminated with mesenchymal and inflammatory cells, compared to UEA-I purified acinar cells. Thus, UEA-I and PNA appear to be excellent lectins for pancreatic acinar cell purification. PNA may be a better choice in situations where mesenchymal cells or inflammatory cells are significantly increased in the pancreas, such as type 1 diabetes, pancreatitis and pancreatic cancer. PMID- 26884344 TI - Impact of insulin-like growth factor-1 receptor and amphiregulin expression on survival in patients with stage II/III gastric cancer enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer. AB - BACKGROUND: Exploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone. METHODS: Formalin-fixed paraffin-embedded surgical specimens from 829 patients were retrospectively examined, and 63 genes were analyzed by quantitative real-time RT PCR after TaqMan assay-based pre-amplification. Gene expression was normalized to the geometric mean of GAPDH, ACTB, and RPLP0 as reference genes, and categorized into low and high values based on the median. The impact of gene expression on survival was analyzed using 5-year survival data. The Benjamini and Hochberg procedure was used to control the false discovery rate. RESULTS: IGF1R and AREG were most strongly correlated with overall survival, which was significantly worse in high IGF1R patients than low IGF1R patients, but better in high AREG patients than low AREG patients. The hazard ratio for death in the analysis of overall survival (S-1 vs. surgery alone) was reduced in the high IGF1R group compared with the low IGF1R group and in the low AREG group compared with the high AREG group. There were no significant interaction effects. CONCLUSION: IGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric cancer, whereas AREG gene expression was associated with good outcomes. No significant interaction effect on survival was evident between S-1 treatment and gene expression. PMID- 26884346 TI - Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells: Direct Contribution of Muse Cells to Tissue Regeneration. AB - While mesenchymal stem cells (MSCs) are easily accessible from mesenchymal tissues, such as bone marrow and adipose tissue, they are heterogeneous, and their entire composition is not fully identified. MSCs are not only able to differentiate into osteocytes, chondrocytes, and adipocytes, which belong to the same mesodermal lineage, but they are also able to cross boundaries between mesodermal, ectodermal, and endodermal lineages, and differentiate into neuronal- and hepatocyte-like cells. However, the ratio of such differentiation is not very high, suggesting that only a subpopulation of the MSCs participates in this cross lineage differentiation phenomenon. We have identified unique cells that we named multilineage-differentiating stress-enduring (Muse) cells that may explain the pluripotent-like properties of MSCs. Muse cells comprise a small percentage of MSCs, are able to generate cells representative of all three germ layers from a single cell, and are nontumorigenic and self-renewable. Importantly, cells other than Muse cells in MSCs do not have these pluripotent-like properties. Muse cells are particularly unique compared with other stem cells in that they efficiently migrate and integrate into damaged tissue when supplied into the bloodstream, and spontaneously differentiate into cells compatible with the homing tissue. Such a repairing action of Muse cells via intravenous injection is recognized in various tissues including the brain, liver, and skin. Therefore, unlike ESCs/iPSCs, Muse cells render induction into the target cell type prior to transplantation unnecessary. They can repair tissues in two simple steps: collection from mesenchymal tissues, such as the bone marrow, and intravenous injection. The impressive regenerative performance of these cells provides a simple, feasible strategy for treating a variety of diseases. This review details the unique characteristics of Muse cells and describes their future application for regenerative medicine. PMID- 26884347 TI - Identification of Mouse Mesenteric and Subcutaneous in vitro Adipogenic Cells. AB - Fat accumulation and the dysfunction of visceral white adipose tissue (WAT), but not subcutaneous WAT, cause abnormalities in whole body metabolic homeostasis. However, no current drugs specifically target visceral WAT. The primary reason for this is that a practical in vitro culture system for mesenteric adipocytes has not been established. To resolve this issue, we sought to identify in vitro adipogenic cells in mesenteric and subcutaneous WATs. First, we examined the expression pattern of surface antigens in stromal-vascular fraction (SVF) cells from mouse mesenteric and subcutaneous WATs, and found the expression of 30 stem cell-related surface antigens. Then, to evaluate the adipogenic ability of each fraction, we performed in vitro screening, and identified five candidate markers for mesenteric adipogenic cells and one candidate marker for subcutaneous adipogenic cells. To investigate whether in vitro adipogenic ability accurately reflects the conditions in vivo, we performed transplantation experiments, and identified CD9(-) CD201(+) Sca-1(-) cells and CD90(+) cells as mesenteric and subcutaneous in vitro adipogenic cells, respectively. Furthermore, mature adipocytes derived from mesenteric and subcutaneous adipogenic cells maintained each characteristic phenotype in vitro. Thus, our study should contribute to the development of a useful culture system for visceral adipocytes. PMID- 26884350 TI - Women show a higher level of anxiety during IVF treatment than men and hold different concerns: a cohort study. AB - PURPOSE: The aim of the present study was to determine levels of anxiety during the course of IVF treatment and gender differences in treatment anxiety. METHODS: This was a prospective cohort study set in a university affiliated, tertiary care IVF program. 119 women and 82 men entering the clinic to undergo IVF treatment filled out questionnaires containing the Spielberger state-trait-anxiety inventory (STAI) as well as further items on specific stress triggers. RESULTS: Women and men undergoing IVF have higher levels of anxiety than the average population in Germany. Overall, female patients show significantly higher values (mean +/- SD) for state and trait anxiety (47.4 +/- 11.0 and 40.1 +/- 9.85) than their male partners (41.4 +/- 9.66 and 35.3 +/- 8.57, p < 0.01). Over the course of several IVF cycles, average STAI scores increased for both genders. When asked about specific stress factors on a 4-point scale from 'not at all' to 'very much so', women report as their main anxiety the failure to achieve a successful pregnancy, scoring significantly higher on questions like 'obtaining a negative pregnancy test' (3.24 +/- 0.82, p < 0.01) and 'disclosure of infertility' (3.02 +/- 1.10, p < 0.001). Their male partners are more concerned about the health risks the women have to take such as 'side effects of ovarian stimulation' (2.55 +/- 0.77, p = 0.002) and 'bleeding or infection after the oocyte aspiration' (2.58 +/- 0.84, p = 0.007). Both genders indicated to be very little worried about multiple pregnancies after IVF. CONCLUSIONS: Women show a higher level of anxiety during IVF treatment and hold different concerns. Neither of the sexes appears to be familiar with the risks associated with multiple pregnancies, a matter that should better be addressed. PMID- 26884348 TI - Tripartite motif 32 prevents pathological cardiac hypertrophy. AB - TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II) mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32 deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. PMID- 26884351 TI - Termination of pregnancy after prenatal diagnosis of spina bifida: a German perspective. AB - PURPOSE: To analyze fetal cases with spina bifida undergoing termination of pregnancy according to chromosomal analysis and further diagnosed sonographic findings. METHODS: Retrospective analysis of cases with spina bifida leading to termination of pregnancy in a tertiary referral center from 2002 to 2011. RESULTS: In the study period, 246 cases of spina bifida were diagnosed in our center and 157 parents chose termination of pregnancy. The time of diagnosis was on average 2 days before the first presentation at our department (22 + 3, range: 12 + 3 - 33 + 3 weeks of gestation). Among 157 pregnancies with spina bifida and termination of pregnancy, further malformations could be detected in 46 (29.3 %) cases. An abnormal karyotype could be found in 13 (18.1 %). Severe ventriculomegaly or mild/moderate ventriculomegaly was present in 109 (69.4 %) and 29 (18.5 %) of the cases, respectively, while banana sign was detectable in 153 cases (97.5 %). In the majority, the upper lesion level was lumbar (71.3 %). In 67 cases (42.7 %), termination of pregnancy took place in or after the 24th week of gestation. CONCLUSION: Direct and indirect signs of spina bifida were detectable in nearly all cases independent of the gestational age. Therefore, the diagnosis could have been made in all cases with late termination. Implementation of a uniform prenatal care including first-trimester scan with potential signs for open spina bifida and second-trimester anomaly scan with indirect intracranial findings and direct detection of spinal lesion could lead to an earlier diagnosis and help to reduce late termination of pregnancy in neural tube defects. PMID- 26884349 TI - Promoter methylation of ITF2, but not APC, is associated with microsatellite instability in two populations of colorectal cancer patients. AB - BACKGROUND: Aberrant Wnt signaling activation occurs commonly in colorectal carcinogenesis, leading to upregulation of many target genes. APC (adenomatous polyposis coli) is an important component of the beta-catenin destruction complex, which regulates Wnt signaling, and is often mutated in colorectal cancer (CRC). In addition to mutational events, epigenetic changes arise frequently in CRC, specifically, promoter hypermethylation which silences tumor suppressor genes. APC and the Wnt signaling target gene ITF2 (immunoglobulin transcription factor 2) incur hypermethylation in various cancers, however, methylation dependent regulation of these genes in CRC has not been studied in large, well characterized patient cohorts. The microsatellite instability (MSI) subtype of CRC, featuring DNA mismatch repair deficiency and often promoter hypermethylation of MutL homolog 1 (MLH1), has a favorable outcome and is characterized by different chemotherapeutic responses than microsatellite stable (MSS) tumors. Other epigenetic events distinguishing these subtypes have not yet been fully elucidated. METHODS: Here, we quantify promoter methylation of ITF2 and APC by MethyLight in two case-case studies nested in population-based CRC cohorts from the Ontario Familial Colorectal Cancer Registry (n = 330) and the Newfoundland Familial Colorectal Cancer Registry (n = 102) comparing MSI status groups. RESULTS: ITF2 and APC methylation are significantly associated with tumor versus normal state (both P < 1.0 * 10(-6)). ITF2 is methylated in 45.8% of MSI cases and 26.9% of MSS cases and is significantly associated with MSI in Ontario (P = 0.002) and Newfoundland (P = 0.005) as well as the MSI-associated feature of MLH1 promoter hypermethylation (P = 6.72 * 10(-4)). APC methylation, although tumor specific, does not show a significant association with tumor subtype, age, gender, or stage, indicating it is a general tumor-specific CRC biomarker. CONCLUSIONS: This study demonstrates, for the first time, MSI-associated ITF2 methylation, and further reveals the subtype-specific epigenetic events modulating Wnt signaling in CRC. PMID- 26884352 TI - Comparison of the symptomatic response in Indian menopausal women with different estrogen preparations for the treatment of menopausal symptoms: a randomized controlled trial. AB - PURPOSE: To compare symptomatic response in Indian women using different estrogen preparations for treatment of menopausal symptoms. METHODOLOGY: A randomized, single blind, four arm, parallel assignment study was conducted in VMMC and SJH, New Delhi, India. 200 Indian menopausal women were recruited and assigned into four treatment groups viz., estradiol valerate (E2V), conjugated equine estrogen (CEE), isoflavones and Placebo group. The statistical significance of categorical variables was determined by Chi-square, Fisher's exact test. In case of quantitative variable parametric test Student's t test was used. In case of quantitative variables where data are not normally distributed, Kruskal-wallis test and Wilcoxon Mann-Whitney test were used. Symptomatic response in vasomotor/vaginal symptoms was assessed in all groups. RESULTS: Both E2V and CEE groups were effective in reducing severity and frequency of hot flashes. 91.9 % decrease was observed in mean hot flash score in the E2V group after 24 weeks of treatment, 89.2 % in the CEE group, 60.42 % decrease in the isoflavones group. While placebo led to 47.9 % decrease in mean hot flash score. After 24 weeks of therapy there was significant increase in vaginal health index in the E2V and CEE and the isoflavones group. No serious side effect was reported in any of the groups. CONCLUSION: Low doses of both CEE and E2V were equally effective for management of vasomotor/vaginal symptoms when administered over 24 weeks. However, it seems more reasonable to replenish with less costly and bio-identical hormone, i.e. micronized estradiol valerate which is equally effective. TRIAL REGISTRY: The trial was registered under Clinical trial registry of India prospectively (number: CTRI/2012/04/002566). PMID- 26884353 TI - Assessing biochar ecotoxicology for soil amendment by root phytotoxicity bioassays. AB - Soil amendment with biochar has been proposed as effective in improving agricultural land fertility and carbon sequestration, although the characterisation and certification of biochar quality are still crucial for widespread acceptance for agronomic purposes. We describe here the effects of four biochars (conifer and poplar wood, grape marc, wheat straw) at increasing application rates (0.5, 1, 2, 5, 10, 20, 50% w/w) on both germination and root elongation of Cucumis sativus L., Lepidium sativum L. and Sorghum saccharatum Moench. The tested biochars varied in chemical properties, depending on the type and quality of the initial feedstock batch, polycyclic aromatic hydrocarbons (PAHs) being high in conifer and wheat straw, Cd in poplar and Cu in grape marc. We demonstrate that electrical conductivity and Cu negatively affected both germination and root elongation at >=5% rate biochar, together with Zn at >=10% and elevated pH at >=20%. In all species, germination was less sensitive than root elongation, strongly decreasing at very high rates of chars from grape marc (>10%) and wheat straw (>50%), whereas root length was already affected at 0.5% of conifer and poplar in cucumber and sorghum, with marked impairment in all chars at >5%. As a general interpretation, we propose here logarithmic model for robust root phytotoxicity in sorghum, based on biochar Zn content, which explains 66% of variability over the whole dosage range tested. We conclude that metal contamination is a crucial quality parameter for biochar safety, and that root elongation represents a stable test for assessing phytotoxicity at recommended in field amendment rates (<1-2%). PMID- 26884354 TI - Characterization of the indoor particles and their sources in an Antarctic research station. AB - Many studies have been carried out on the environmental impact of the research stations on the Antarctic continent. However, the assessment of indoor air quality in these confined environments has been neglected. The main objectives of this study are to investigate the granulometric distribution of the indoor particles in the different compartments of the Brazilian Antarctic Station, to examine the number and mass concentration of the indoor particles, to conduct chemical and morphological analyses of the indoor PM2.5, and to identify the possible sources of the PM. The results showed that Na, K, Cl, Fe, Zn, S and Si were the main elements detected. High levels of black carbon were recorded in the workshop, which may be associated with the use of diesel vehicles. To identify the human activities related to the indoor particle emission in the station, the size distribution of the particles in the living room was monitored for seven consecutive days, during normal station operation. It was possible to identify the influence of individual processes, such as incineration, cooking and the movement of people, upon the particle size number concentration. The indoor/outdoor (I/O) ratio for the total suspended particles (TSP), PM10, PM2.5 and PM1 measured was significantly larger than those reported for urban buildings. In general, the I/O ratio distribution for all the compartments shows peak values between 2.5 and 10 MUm, which is often related to human activity, such as cleaning, personnel circulation or clothing surfaces. The maximum I/O ratio at this range varied from 12 to 60. In addition, the compartments affected by combustion processes tend to present a significant number of submicron particles. PMID- 26884355 TI - Dissipation dynamics and final residues of cloransulam-methyl in soybean and soil. AB - This work is the first report on the dissipation and final residue of cloransulam methyl on soybean plant at field conditions. A fast, simple, and reliable residue analytical method for determination of cloransulam-methyl in soybean matrices and soil was developed based on quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) detection. The average recoveries of cloransulam-methyl in soybean matrices and soil ranged from 80 to 105%, with RSDs between 3-11%. The limit of detection (LOD) was 0.001 mg kg(-1) for soybean grain, plant, and soil and was 0.005 mg kg(-1) for soybean straw. This method was then used to characterize dissipation of cloransulam-methyl in soybeans and soil from three locations in China for the first time. Cloransulam-methyl dissipated quickly in soybean plant with half-lives (T1/2) of 0.21-0.56 days. The dissipation dynamic in soil was characterized using both first-order kinetics model and two-compartment model, and the half-lives were similar, ranging from 0.44 to 5.53 days at three experimental sites in 2012 and 2013. The final residue data showed a very low level of cloransulam-methyl in soil (<=0.026 mg kg(-1)), soybean grain (<=0.001 mg kg(-1)), and straw (<=0.005 mg kg(-1)) samples at harvest time. With the faster and simple analytical method on soybean and soil, rapid dissipation of cloransulam-methyl was observed at three geospatial locations in China, and the terminal residue levels were negligible, so mammalian ingestion exposure is minimal. PMID- 26884356 TI - Performance assessment of geospatial simulation models of land-use change--a landscape metric-based approach. AB - Performance evaluation is a critical step when developing land-use and cover change (LUCC) models. The present study proposes a spatially explicit model performance evaluation method, adopting a landscape metric-based approach. To quantify GEOMOD model performance, a set of composition- and configuration-based landscape metrics including number of patches, edge density, mean Euclidean nearest neighbor distance, largest patch index, class area, landscape shape index, and splitting index were employed. The model takes advantage of three decision rules including neighborhood effect, persistence of change direction, and urbanization suitability values. According to the results, while class area, largest patch index, and splitting indices demonstrated insignificant differences between spatial pattern of ground truth and simulated layers, there was a considerable inconsistency between simulation results and real dataset in terms of the remaining metrics. Specifically, simulation outputs were simplistic and the model tended to underestimate number of developed patches by producing a more compact landscape. Landscape-metric-based performance evaluation produces more detailed information (compared to conventional indices such as the Kappa index and overall accuracy) on the model's behavior in replicating spatial heterogeneity features of a landscape such as frequency, fragmentation, isolation, and density. Finally, as the main characteristic of the proposed method, landscape metrics employ the maximum potential of observed and simulated layers for a performance evaluation procedure, provide a basis for more robust interpretation of a calibration process, and also deepen modeler insight into the main strengths and pitfalls of a specific land-use change model when simulating a spatiotemporal phenomenon. PMID- 26884357 TI - Effects of field storage method on E. coli concentrations measured in storm water runoff. AB - Storm water runoff is increasingly assessed for fecal indicator organisms (e.g., Escherichia coli, E. coli) and its impact on contact recreation. Concurrently, use of autosamplers along with logistic, economic, technical, and personnel barriers is challenging conventional protocols for sample holding times and storage conditions in the field. A common holding time limit for E. coli is 8 h with a 10 degrees C storage temperature, but several research studies support longer hold time thresholds. The use of autosamplers to collect E. coli water samples has received little field research attention; thus, this study was implemented to compare refrigerated and unrefrigerated autosamplers and evaluate potential E. coli concentration differences due to field storage temperature (storms with holding times <=24 h) and due to field storage time and temperature (storms >24 h). Data from 85 runoff events on four diverse watersheds showed that field storage times and temperatures had minor effects on mean and median E. coli concentrations. Graphs and error values did, however, indicate a weak tendency for higher concentrations in the refrigerated samplers, but it is unknown to what extent differing die-off and/or regrowth rates, heterogeneity in concentrations within samples, and laboratory analysis uncertainty contributed to the results. The minimal differences in measured E. coli concentrations cast doubt on the need for utilizing the rigid conventional protocols for field holding time and storage temperature. This is not to say that proper quality assurance and quality control is not important but to emphasize the need to consider the balance between data quality and practical constraints related to logistics, funding, travel time, and autosampler use in storm water studies. PMID- 26884358 TI - Antibiotic resistance and plasmid profiling of Vibrio spp. in tropical waters of Peninsular Malaysia. AB - Vibrio species isolated from four different sampling stations in the west coast of Peninsular Malaysia were screened for their antimicrobial resistance and plasmid profiles. A total of 138 isolates belonging to 15 different species were identified. Vibrio campbellii, V. parahaemolyticus, V. harveyi, and V. tubiashii were found to predominance species at all stations. High incidence of erythromycin, ampicillin, and mecillinam resistance was observed among the Vibrio isolates. In contrast, resistance against aztreonam, cefepime, streptomycin, sulfamethoxazole, and sulfonamides was low. All the Vibrio isolates in this study were found to be susceptible to imipenem, norfloxacin, ofloxacin, chloramphenicol, trimethoprim/sulfamethoxazole, and oxytetracycline. Ninety-five percent of the Vibrio isolates were resistant to one or more different classes of antibiotic, and 20 different resistance antibiograms were identified. Thirty-two distinct plasmid profiles with molecular weight ranging from 2.2 to 24.8 kb were detected among the resistance isolates. This study showed that multidrug resistant Vibrio spp. were common in the aquatic environments of west coast of Peninsular Malaysia. PMID- 26884360 TI - What can Neighbourhood Density effects tell us about word learning? Insights from a connectionist model of vocabulary development. AB - In this paper, we investigate the effect of neighbourhood density (ND) on vocabulary size in a computational model of vocabulary development. A word has a high ND if there are many words phonologically similar to it. High ND words are more easily learned by infants of all abilities (e.g. Storkel, 2009; Stokes, 2014). We present a neural network model that learns general phonotactic patterns in the exposure language, as well as specific word forms and, crucially, mappings between word meanings and word forms. The network is faster at learning frequent words, and words containing high-probability phoneme sequences, as human word learners are, but, independently of this, the network is also faster at learning words with high ND, and, when its capacity is reduced, it learns high ND words in preference to other words, similarly to late talkers. We analyze the model and propose a novel explanation of the ND effect, in which word meanings play an important role in generating word-specific biases on general phonological trajectories. This explanation leads to a new prediction about the origin of the ND effect in infants. PMID- 26884361 TI - An Analysis of Adverse Event Reporting in Balloon Sinus Procedures. AB - OBJECTIVE: (1) Become familiar with reported adverse events related to balloon dilation of the paranasal sinus ostia. (2) Understand the sequelae occurring with these events. STUDY DESIGN: Retrospective analysis of a prospective database. SETTING: OpenFDA database. SUBJECTS AND METHODS: The OpenFDA program website of the Food and Drug Administration was queried with the Application Program Interface query system for medical device adverse events involving balloon devices for the dilation of paranasal sinus ostia from January 2006 through December 2014. The raw data were then tabulated, with adverse events codified by event type, sinus involved, injury type, device malfunction, surgeon error, and qualitative data. Sequelae were also quantified. RESULTS: In sum, 114 adverse events were identified. Patient injury was the most frequently reported adverse event (n = 72), followed by 36 device malfunctions, 4 deaths, and 2 unclassified. The most common injury involved orbital complications, including 23 (20.2%) orbital wall fractures and 22 (19.3%) postseptal and 22 (19.3%) preseptal orbital injuries. In addition, there were 17 (14.9%) skull base injuries and 7 (6.1%) cases of severe epistaxis observed; 11 (9.6%) cases mentioned surgeon error. Cerebrospinal fluid leak was significantly associated with frontal surgery (P = .002) and sphenoid surgery (P = .001), whereas post- and preseptal orbital injury was associated with maxillary surgery (P = .017 and P = .002). Epistaxis was associated with sphenoid surgery (P = .032). CONCLUSIONS: Based on the number of balloon sinus procedures performed, Food and Drug Administration-reported adverse events are uncommon, although a select portion can be severe. Surgeons should be aware of different complications reported with specific sinuses addressed with balloon techniques. PMID- 26884362 TI - Implementation of a Pediatric Posttonsillectomy Pain Protocol in a Large Group Practice. AB - OBJECTIVE: In response to the increased risk of respiratory failure and death after tonsillectomy related to codeine use, Kaiser Permanente Northwest restricted use of opioids in patients <7 years old via electronic health record (EHR). However, opioids could be prescribed at physician discretion by overriding the EHR. This study aims to examine protocol compliance in a large group practice using EHR order sets and complication rates as compared with historical data. STUDY DESIGN: Case series with chart review. SETTING: Ambulatory care within a health maintenance organization. SUBJECTS AND METHODS: Procedural codes were used to identify children <7 years old who underwent tonsillectomy or adenotonsillectomy approximately 1.5 years before and after implementation of EHR protocol (n = 437). Primary outcome was opioid pain prescriptions received by patients. Secondary outcomes were emergency or urgent care utilization, postoperative bleeding, nausea, vomiting, dehydration, death, and reasons for prescribing opioid pain medication after EHR protocol implementation. Chi-square analysis and Fischer's exact testing were used to compare differences in event rates. RESULTS: Implementation of an age-based narcotic protocol significantly decreased physician narcotic prescribing from 82.2% to 15.4% (P < .0001). The most common reason for narcotic prescription after the intervention was the report of inadequate pain control by phone call (35%). There was no significant difference in rate of emergency or urgent care utilization between pre- and postimplementation groups (4% vs 6%, P = .29). CONCLUSIONS: Implementation of an age-based narcotic restriction for posttonsillectomy patients using an EHR order set is an effective and safe way to influence physician prescription practices. PMID- 26884363 TI - Systematic Review on Surgical Outcomes and Hearing Preservation for Cochlear Implantation in Children and Adults. AB - OBJECTIVE: The mastoidectomy with facial recess approach (MFRA) is considered the reference standard for cochlear implantation. The suprameatal approach (SMA) was developed more recently and does not require mastoidectomy, which could influence postoperative outcomes. We aim to identify the optimal operative approach for cochlear implantation based on postoperative complications and hearing preservation in children and adults. DATA SOURCES: PubMed, EMBASE, Scopus, and Google Scholar. REVIEW METHODS: Studies comparing MFRA and SMA in children and adults were eligible for inclusion. Original reports with moderate relevance and validity were included. Relevance and validity were assessed with a self-modified critical appraisal tool. This review was reported in accordance to PRISMA guidelines. RESULTS: We retrieved 294 citations. Only retrospective nonrandomized studies were identified (level III evidence). Six articles were selected for full text inclusion and 4 articles for data extraction. No article found a significant difference between MFRA and SMA with respect to postoperative complications in children and adults. One study found a significantly (P < .023) higher pediatric MFRA mastoiditis rate; however, meta-analysis did not indicate an overall effect. Hearing preservation was reported only in adults, and outcomes between techniques did not differ. CONCLUSION: No evidence was noted for lower complication rates or improved hearing preservation between the MFRA and SMA for cochlear implantation in children and adults. Pediatric data were available for children implanted above the age of 24 months only. Level I evidence is needed to resolve the uncertainty regarding differences in postoperative outcomes of pediatric and adult MFRA and SMA. PMID- 26884364 TI - 2015 Equilibrium Committee Amendment to the 1995 AAO-HNS Guidelines for the Definition of Meniere's Disease. AB - Meniere's disease is a disorder of the inner ear that causes attacks of vertigo and hearing loss, tinnitus, aural fullness in the involved ear. Over the past 4 decades, the Equilibrium Committee of the AAO-HNS has issued guidelines for diagnostic criteria, with the latest version being published in 1995. These criteria were reviewed in 2015 by the Equilibrium Committee, and revisions were approved at the recent meeting of the committee at the 2015 AAO-HNSF Annual Meeting. The following commentary outlines the amended and approved criteria. PMID- 26884366 TI - Extracapsular Dissection with Facial Nerve Dissection for Benign Parotid Tumors. PMID- 26884365 TI - Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy. AB - OBJECTIVES: The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary academic center. SUBJECTS: Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. METHODS: We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed. RESULTS: Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). CONCLUSION: Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins. PMID- 26884367 TI - Acute Invasive Fungal Rhinosinusitis: A 15-Year Experience with 41 Patients. AB - OBJECTIVES: To describe a 15-year single-institution experience of 41 cases of acute invasive fungal sinusitis (AIFRS), identify clinical indicators predictive of AIFRS, and discuss our approach to these high-acuity patients. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center; The Pennsylvania State University Hershey Medical Center. SUBJECTS AND METHODS: A retrospective review was performed for AIFRS consultations between September 1999 and March 2014. Variables reviewed included underlying condition, presenting symptoms, absolute neutrophil count, disease extent on examination, radiographic findings, medical treatment, biopsy results, surgical treatment, and outcomes. Univariate analysis was performed to determine variables significantly associated with AIFRS. Outcome measures were assessed and patient assessment algorithm developed. RESULTS: Of 131 patients evaluated, 41 were diagnosed with AIFRS; 92.7% had an underlying hematologic malignancy. Disease predictive variables included absolute neutrophil count <500/MUL (P < .0001; sensitivity = 78%), mucosal abnormalities of middle turbinate (P < .0001; specificity = 88%) and septum (P < .0001; specificity = 97%), and specifically, necrosis of the middle turbinate (P < .0001; specificity = 97%). Twenty-five AIFRS patients (61%) survived until discharge; 25% (n = 10) expired secondary to AIFRS infection explicitly. CONCLUSION: This series represents one of the largest single institution experiences of AIFRS published to date. Timely diagnosis is necessary to improve patient outcomes and limit morbidity. Maintaining a high index of suspicion in at-risk patient populations, followed by prompt evaluation and management, is crucial in suspected AIFRS. The presence or absence of certain findings appear to correlate with biopsy results and may aid in appropriately gauging clinical suspicion for the presence of AIFRS. PMID- 26884368 TI - Utility of Surgery/Radiotherapy in Distant Metastatic Head and Neck Squamous Cell Carcinoma: A Population-Based Approach. AB - OBJECTIVES: The aim of this study is to analyze the survival benefits of surgery and/or radiation therapy over no therapy in patients with metastatic (M1) squamous cell carcinoma of the head and neck region (HN-SCC). STUDY DESIGN: Retrospective administrative database analysis. SUBJECTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for M1 HN SCC cases from 1988 to 2012 (6663 patients). Patient demographics, initial treatment, and survival outcomes were analyzed. Survival was analyzed with the Kaplan-Meier model. RESULTS: Of the 6663 patients identified with M1 HN-SCC in the SEER database, 1669 patients received no therapy; 2459 patients, radiotherapy; 570 patients, surgery; and 1100 patients, surgery with adjuvant radiotherapy. The mean survival was 8.44 months for patients who did not undergo any therapy. In comparison, patients who underwent radiotherapy alone, surgery alone, or surgery with radiotherapy had mean survivals of 18.03 (P < .0001), 31.07 (P < .0001), and 39.93 (P < .0001) months, respectively. The 5-year disease specific survival rates were 6.35% for no therapy, 17.51% for radiotherapy alone, 30.50% for surgery alone, and 33.75% for surgery with radiotherapy (P < .0001). Site-specific analysis revealed that surgery and/or radiation provides disease specific survival benefit as compared with no therapy at all subsites within the head and neck region. CONCLUSIONS: Surgery and/or radiation-which has been shown to improve quality of life in patients with advanced cancer-is associated with an increased survival when utilized in patients with distant metastatic disease. PMID- 26884369 TI - Tracheostomy Complications in Institutionalized Children with Long-term Tracheostomy and Ventilator Dependence. AB - OBJECTIVES: (1) To identify tracheostomy complications in institutionalized children with chronic tracheostomy. (2) To determine factors that predispose to development of tracheostomy complications in institutionalized children with chronic tracheostomy. STUDY DESIGN: Case series with chart review over 10 years. SETTING: Tertiary children's hospital. SUBJECTS AND METHODS: Children were included if they underwent tracheostomy before 21 years of age and resided at a pediatric nursing facility. Most children were ventilator dependent and had severe comorbid medical conditions, including developmental delay and cerebral palsy. The number of tracheostomy complications and unplanned hospital admissions were recorded. Interventions for tracheostomy complications were also reviewed. RESULTS: Thirty-two institutionalized children with chronic tracheostomy were included. The mean age at time of tracheostomy was 5.4 years, with a mean duration of institutionalization of 9.1 years. Twenty-seven children (84%) experienced tracheostomy complications. The total number of complications was 79. The most common tracheostomy complications identified were peristomal granulation (n = 13) and suprastomal granulation (n = 12). Age at time of tracheostomy, duration of institutionalization, and ventilator dependence did not predict the likelihood of developing a complication. Of 32 patients, 20 were evaluated in the emergency room during the study, and there were 48 unplanned admissions for tracheostomy-related complications during the study. Forty-five urgent direct laryngoscopy and bronchoscopy procedures were performed in a total of 20 children with tracheostomy complications. CONCLUSIONS: Tracheostomy complications are common in institutionalized children with chronic tracheostomy and are challenging to manage. Further research is necessary to determine novel ways to reduce tracheostomy complications in this population. PMID- 26884359 TI - Genetic predisposition to ductal carcinoma in situ of the breast. AB - BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. RESULTS: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist. PMID- 26884370 TI - Radiologic Evidence of Cochlear Implant Bone Bed Formation Following the Subperiosteal Temporal Pocket Technique. AB - OBJECTIVE: To compare the thicknesses of bone beneath the internal receiver stimulator (IRS) with the symmetric contralateral unimplanted side in postoperative temporal high-resolution computed tomography (CT) and/or cranial CT of the patients for whom cochlear implants were secured by the subperiosteal temporal pocket technique. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care hospital, cochlear implant referral center. SUBJECTS: Cochlear implanted pediatric patients with postoperative temporal high-resolution CT and/or cranial CT were reviewed. The study group included 10 patients with Clarion devices (Advanced Bionics, Valencia, California). METHODS: Thicknesses of bone were recorded independently by 2 radiologists in the standardized coordinates of proximal, middle, and distal segments of both the IRS bed and the contralateral unimplanted side in each patient. Bone thickness differences in the proximal, middle, and distal segments of IRS were investigated. Any correlation between bone thickness differences and patient age at implantation or duration of implantation was also investigated. RESULTS: Mean values of bone thicknesses obtained from the IRS side and contralateral unimplanted side were, respectively, as follows: 2.40 +/- 0.80 mm and 4.17 +/- 1.10 mm in the proximal segment (P = .0001); 1.48 +/- 0.33 mm and 3.02 +/- 0.85 mm in the middle segment (P = .0001); and 2.13 +/- 0.41 mm and 3.40 +/- 0.61 mm in the distal segment (P = .006). Significant positive correlation was found between patient age at implantation and decrement values in the distal segments (r = 0.681, P = .03). CONCLUSION: The subperiosteally secured IRS eventually creates its own well on the skull vault. This new radiologic evidence shows that device migration risk decreases over time, and it supports the findings of other clinical series showing device stability using the subperiosteal pocket technique. PMID- 26884371 TI - A Pediatric Decannulation Protocol: Outcomes of a 10-Year Experience. AB - OBJECTIVES: (1) Describe an institutional protocol that focuses on the essential steps for decannulation of pediatric patients with long-term tracheostomies. (2) Discuss the preliminary observations of the safety of this protocol in regard to decannulation failures and successes in a selected patient population. STUDY DESIGN: Case series with chart review. SETTING: A tertiary pediatric hospital. SUBJECTS: Subjects were pediatric patients with chronic tracheostomies undergoing decannulation. Ages ranged from 1 to 17 years old. Indications for initial tracheostomy included chronic lung disease, airway obstruction, and trauma. METHODS: Subjects underwent decannulation attempt following a specific protocol. The protocol consisted of operative laryngoscopy and bronchoscopy. If the airway was deemed adequate for decannulation at that time, the tracheotomy tube was removed, and the child was monitored overnight; the patient was considered for discharge the following day if no complications arose. No routine capping, downsizing, or polysomnography was performed. RESULTS: Thirty-five patients fit the criteria and were decannulated within 24 hours of endoscopy. Successful decannulation served as the primary outcome. Of the 35 decannulated patients, 54% (n = 19) were discharged the day following decannulation and another 37% (n = 13) on postdecannulation day 2. There were no acute failures or readmissions. Average inpatient stay for those decannulated was 1.8 days. CONCLUSION: This study describes the preliminary observations of a decannulation protocol in a small subset of patients. The protocol resulted in no acute failures and offers a conservative approach to resource utilization, making it unique when compared with other published protocols. PMID- 26884372 TI - Ovarian cancer survivors' quality of life: a systematic review. AB - PURPOSE: The assessment of quality of life (QOL) among ovarian cancer (OC) patients has mainly focused on the acute phase of treatment. This systematic review examines studies measuring QOL in patients who survived OC after treatment and synthesizes results in order to assess QOL and patient-reported outcome (PRO) data at long-term follow-up. METHODS: Articles published in English between 1990 to November 2014 were identified with the databases MEDLINE and PubMed, using the specific keywords "OC survivors" combined with the terms, "QOL," "health-related QOL," and "PROs." Data were reviewed for design, time since end of treatment, measurement tools, and outcomes (categorized in three topics: global QOL compared to controls, treatment sequelae, and intervention strategies). RESULTS: The initial search strategy provided 148 articles of which 31 were considered eligible. Most studies focused on epithelial OC, and only a few studies investigated survivors of ovarian germ cell tumor. More than 60 instruments of QOL measures were used in the corpus. Despite the persistence of psychological and physical symptoms, treatment sequelae, sexual problems, and fear of recurrence in some survivors, most studies demonstrated that OC survivors generally have good QOL compared to healthy women. Studies proposing interventions are lacking. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVOR: OC survivors experience a wide range of sequelae that may persist for a long time and negatively impact QOL. Further large-scale research is needed to fully understand problems that have significant effects on QOL, in order to develop interventions and treatments suitable for women at need. PMID- 26884373 TI - Antibodies from donor B cells perpetuate cutaneous chronic graft-versus-host disease in mice. AB - Cutaneous sclerosis is one of the most common clinical manifestations of chronic graft-versus-host disease (cGVHD). Donor CD4(+) T and B cells play important roles in cGVHD pathogenesis, but the role of antibodies from donor B cells remains unclear. In the current studies, we generated immunoglobulin (Ig)H(ugamma1) DBA/2 mice whose B cells have normal antigen-presentation and regulatory functions but cannot secrete antibodies. With a murine cGVHD model using DBA/2 donors and BALB/c recipients, we have shown that wild-type (WT) grafts induce persistent cGVHD with damage in the thymus, peripheral lymphoid organs, and skin, as well as cutaneous T helper 17 cell (Th17) infiltration. In contrast, IgH(ugamma1) grafts induced only transient cGVHD with little damage in the thymus or peripheral lymph organs or with little cutaneous Th17 infiltration. Injections of IgG-containing sera from cGVHD recipients given WT grafts but not IgG-deficient sera from recipients given IgH(ugamma1) grafts led to deposition of IgG in the thymus and skin, with resulting damage in the thymus and peripheral lymph organs, cutaneous Th17 infiltration, and perpetuation of cGVHD in recipients given IgH(ugamma1) grafts. These results indicate that donor B-cell antibodies augment cutaneous cGVHD in part by damaging the thymus and increasing tissue infiltration of pathogenic Th17 cells. PMID- 26884375 TI - Spatially divergent clonal evolution in multiple myeloma: overcoming resistance to BRAF inhibition. PMID- 26884374 TI - Early cytomegalovirus reactivation remains associated with increased transplant related mortality in the current era: a CIBMTR analysis. AB - Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for International Blood and Marrow Transplant Research (CIBMTR) Database was interrogated to analyze the impact of CMV reactivation on hematologic disease relapse in the current era. Data from 9469 patients transplanted with bone marrow or peripheral blood between 2003 and 2010 were analyzed according to 4 disease categories: AML (n = 5310); acute lymphoblastic leukemia (ALL, n = 1883); chronic myeloid leukemia (CML, n = 1079); and myelodysplastic syndrome (MDS, n = 1197). Median time to initial CMV reactivation was 41 days (range, 1-362 days). CMV reactivation had no preventive effect on hematologic disease relapse irrespective of diagnosis. Moreover, CMV reactivation was associated with higher nonrelapse mortality [relative risk [RR] among disease categories ranged from 1.61 to 1.95 and P values from .0002 to <.0001; 95% confidence interval [CI], 1.14-2.61). As a result, CMV reactivation was associated with lower overall survival for AML (RR = 1.27; 95% CI, 1.17-1.38; P <.0001), ALL (RR = 1.46; 95% CI, 1.25-1.71; P <.0001), CML (RR = 1.49; 95% CI, 1.19-1.88; P = .0005), and MDS (RR = 1.31; 95% CI, 1.09-1.57; P = .003). In conclusion, CMV reactivation continues to remain a risk factor for poor posttransplant outcomes and does not seem to confer protection against hematologic disease relapse. PMID- 26884376 TI - Cardiac changes in pediatric liver transplant recipients: are they truly irreversible? PMID- 26884377 TI - Later-borns Don't Give Up: The Temporary Effects of Birth Order on European Earnings. AB - The existing empirical evidence on the effects of birth order on wages does not distinguish between temporary and permanent effects. Using data from 11 European countries for males born between 1935 and 1956, we show that firstborns enjoy on average a 13.7% premium in their entry wage compared with later-borns. This advantage, however, is short-lived and disappears 10 years after labor market entry. Although firstborns start with a better job, partially because of their higher education, later-borns quickly catch up by switching earlier and more frequently to better-paying jobs. We argue that a key factor driving our findings is that later-borns have lower risk aversion than firstborns. PMID- 26884378 TI - Agreement in hemodynamic monitoring during orthotopic liver transplantation: a comparison of FloTrac/Vigileo at two monitoring sites with pulmonary artery catheter thermodilution. AB - To study agreement in cardiac index (CI), systemic vascular resistance index (Systemic VRI) and stroke volume variation (SV variation) between the FloTrac/Vigileo at radial and femoral arterial cannulation sites, and pulmonary artery catheter (PAC) thermodilution, in patients undergoing orthotopic liver transplantation. A prospective observational study of 25 adult patients with liver failure. Radial and femoral arteries were cannulated with standardised FloTrac/Vigileo arterial transducer kits and a PAC was inserted. CI, SV variation and Systemic VRI were measured four times (30 min after induction of anesthesia, 30 min after portal vein clamping, 30 min after graft reperfusion, 30 min after commencement of bile duct anastomosis). The bias, precision, limits of agreement (LOA) and percentage errors were calculated using Bland-Altman statistics to compare measurements from radial and femoral arterial cannulation sites and PAC thermodilution. Neither radial nor femoral CI achieved acceptable agreement with PAC CI [radial to PAC bias (SD) 1.17 (1.49) L/min/m2, percentage error 64.40 %], [femoral to PAC bias (SD) -0.71 (1.81) L/min/m2, percentage error 74.20 %]. Agreement between radial and femoral sites for CI [mean difference (SD) -0.43 (1.51) L/min/m2, percentage error 70.40 %] and Systemic VRI [mean difference (SD) 0.03 (4.17) LOA +/-8.17 mmHg min m2/L] were also unacceptable. Agreement in SV variation between radial and femoral measurement sites approached a clinically acceptable threshold [mean difference (SD) 0.68 (2.44) %), LOA +/-4.78 %]. FloTrac/Vigileo CI cannot substitute for PAC thermodilution CI, regardless of measurement site. SV variation measurements may be interchangeable between radial and femoral sites for determining fluid responsiveness. PMID- 26884379 TI - Rehabilitation following carpal tunnel release. AB - BACKGROUND: Various rehabilitation treatments may be offered following carpal tunnel syndrome (CTS) surgery. The effectiveness of these interventions remains unclear. This is the first update of a review first published in 2013. OBJECTIVES: To review the effectiveness and safety of rehabilitation interventions following CTS surgery compared with no treatment, placebo, or another intervention. SEARCH METHODS: On 29 September 2015, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL Plus, AMED, LILACS, and PsycINFO. We also searched PEDro (3 December 2015) and clinical trials registers (3 December 2015). SELECTION CRITERIA: Randomised or quasi-randomised clinical trials that compared any postoperative rehabilitation intervention with either no intervention, placebo, or another postoperative rehabilitation intervention in individuals who had undergone CTS surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, assessed risk of bias, and assessed the quality of the body of evidence for primary outcomes using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach according to standard Cochrane methodology. MAIN RESULTS: In this review we included 22 trials with a total of 1521 participants. Two of the trials were newly identified at this update. We studied different rehabilitation treatments including immobilisation using a wrist orthosis, dressings, exercise, controlled cold therapy, ice therapy, multi-modal hand rehabilitation, laser therapy, electrical modalities, scar desensitisation, and arnica. Three trials compared a rehabilitation treatment to a placebo, four compared rehabilitation to a no treatment control, three compared rehabilitation to standard care, and 15 compared various rehabilitation treatments to one another.Overall, the included studies were very low in quality. Thirteen trials explicitly reported random sequence generation; of these, five adequately concealed the allocation sequence. Four trials achieved blinding of both participants and outcome assessors. Five were at high risk of bias from incompleteness of outcome data at one or more time intervals, and eight had high risk of selective reporting bias.These trials were heterogeneous in terms of treatments provided, duration of interventions, the nature and timing of outcomes measured, and setting. Therefore, we were not able to pool results across trials.Four trials reported our primary outcome, change in self reported functional ability at three months or more. Of these, three trials provided sufficient outcome data for inclusion in this review. One small high-quality trial studied a desensitisation programme compared with standard treatment and revealed no statistically significant functional benefit based on the Boston Carpal Tunnel Questionnaire (BCTQ) (mean difference (MD) -0.03, 95% confidence interval (CI) -0.39 to 0.33). One low-quality trial assessed participants six months post surgery using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and found no significant difference between a no formal therapy group and a group given a two-week course of multi-modal therapy commenced at five to seven days post surgery (MD 1.00, 95% CI -4.44 to 6.44). One very low quality quasi-randomised trial found no statistically significant difference in function on the BCTQ at three months post surgery with early immobilisation (plaster wrist orthosis worn until suture removal) compared with a splint and late mobilisation (MD 0.39, 95% CI -0.45 to 1.23).Differences between treatments for secondary outcome measures (change in self reported functional ability measured at less than three months; change in CTS symptoms; change in CTS-related impairment measures; presence of iatrogenic symptoms from surgery; return to work or occupation; and change in neurophysiological parameters) were generally small and not statistically significant. Few studies reported adverse events. AUTHORS' CONCLUSIONS: There is limited and, in general, low quality evidence for the benefit of the reviewed interventions. People who have undergone CTS surgery should be informed about the limited evidence of effectiveness of postoperative rehabilitation interventions. Until researchers provide results of more high quality trials that assess the effectiveness and safety of various rehabilitation treatments, the decision to provide rehabilitation following CTS surgery should be based on the clinician's expertise, the patient's preferences and the context of the rehabilitation environment. It is important for researchers to identify patients who respond to a particular treatment and those who do not, and to undertake high-quality studies that evaluate the severity of iatrogenic symptoms from surgery, measure function and return-to-work rates, and control for confounding variables. PMID- 26884380 TI - Multidimensional Predictors of Treatment Outcome in Usual Care for Adolescent Conduct Problems and Substance Use. AB - This study investigated baseline client characteristics that predicted long-term treatment outcomes among adolescents referred from school and community sources and enrolled in usual care for conduct and substance use problems. Predictor effects for multiple demographic (age, sex, race/ethnicity), clinical (baseline symptom severity, comorbidity, family discord), and developmental psychopathology (behavioral dysregulation, depression, peer delinquency) characteristics were examined. Participants were 205 adolescents (52 % male; mean age 15.7 years) from diverse backgrounds (59 % Hispanic American, 21 % African American, 15 % multiracial, 6 % other) residing in a large inner-city area. As expected, characteristics from all three predictor categories were related to various aspects of change in externalizing problems, delinquent acts, and substance use at one-year follow-up. The strongest predictive effect was found for baseline symptom severity: Youth with greater severity showed greater clinical gains. Higher levels of co-occurring developmental psychopathology characteristics likewise predicted better outcomes. Exploratory analyses showed that change over time in developmental psychopathology characteristics (peer delinquency, depression) was related to change in delinquent acts and substance use. Implications for serving multiproblem adolescents and tailoring treatment plans in routine care are discussed. PMID- 26884382 TI - Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. AB - Emergence of thermogenic adipocytes such as brown and beige adipocytes is critical for whole body energy metabolism. Promoting the emergence of these adipocytes, which increase energy expenditure, could be a viable strategy in treating obesity and its related diseases. However, little is known regarding the mechanisms that regulate the emergence of these adipocytes in obese adipose tissue. Here, we demonstrated that classically activated macrophages (M1 Mphi) suppress the induction of thermogenic adipocytes in obese adipose tissues of mice. Cold exposure significantly induced the expression levels of uncoupling protein-1 (UCP1), which is a mitochondrial protein unique in thermogenic adipocytes, in C57BL/6 mice fed a normal diet. However, UCP1 induction was significantly suppressed in adipose tissues of C57BL/6 mice fed a high-fat diet, into which M1 Mphi infiltrated. Depletion of M1 Mphi using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-alpha (TNFalpha) in the adipose tissues. Importantly, consistent with the observed changes in the expression levels of marker genes for thermogenic adipocytes, combination treatment of clodronate liposome and cold exposure resulted in metabolic benefits such as lowered body weight and blood glucose level in obese mice. Moreover, intraperitoneal injection of recombinant TNFalpha protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 Mphi suppress the induction of thermogenic adipocytes in obese adipose tissues via TNFalpha. This report suggests that inflammation induced by infiltrated Mphi could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues. PMID- 26884381 TI - Risk stratification and predictive risk-scoring model for lymph node metastasis in early gastric cancer. AB - BACKGROUND: We are increasingly experiencing difficulty in deciding whether to perform gastrectomy after noncurative endoscopic resection of early gastric cancer (EGC) for patients at high risk for surgery. If the differences in risk for lymph node metastasis (LNM) on the basis of noncurative status are understood, the decision becomes easier. The present study aimed to stratify the LNM risk and develop and validate a risk-scoring model for predicting LNM. METHODS: By retrospectively reviewing 3131 patients with solitary EGC who underwent gastrectomy with lymphadenectomy at our institution between July 1997 and May 2013, LNM risk was stratified and a risk-scoring model was developed on the basis of the identified independent risk factors for LNM. The scoring was validated using 352 other surgically resected EGC cases. The discriminatory accuracy of the scoring was measured by area under receiver operating characteristic curve (AUROC). RESULTS: LNM was detected in 386 of 3131 cases. LNM risk in each subgroup, stratified by the identified independent risk factors, such as tumor size, depth, histological type, ulcerative findings, and lymphovascular involvement, considerably varied from 0 % to >50 % even among the current guidelines' noncurative subgroups. An 11-point scoring model was built, and AUROCs were 0.84 (95 % confidence interval, 0.82-0.86) and 0.82 (0.75-0.88) in the development and validation sets, respectively. CONCLUSIONS: The present study revealed detailed LNM risk stratification data, and developed and validated an 11-point scoring model. PMID- 26884383 TI - Direct regulation of IGF-binding protein 1 promoter by interleukin-1beta via an insulin- and FoxO-1-independent mechanism. AB - The level of insulin-like growth factor-binding protein 1 (IGFBP1), a liver produced serum protein that regulates insulin-like growth factor-I bioactivity, glucose homeostasis, and tissue regeneration, increases during inflammation. This manuscript describes a novel pathway for the regulation of hepatic IGFBP1 mRNA and protein levels by interleukin (IL)-1beta. Experiments with the luciferase reporter system show that IL-1beta stimulates transcriptional activity from the 1 kb promoter region of IGFBP1. Although IL-1beta stimulation suppresses the insulin activation of protein kinase B, the major upstream regulator of IGFBP1 mRNA transcription, the induction of IGFBP1 by IL-1beta did not require an intact insulin response element. Furthermore, neither overexpression nor silencing of FoxO-1 had any effect on the IL-1beta-induced increase in IGFBP1 mRNA levels and promoter activity. However, inhibition of the ERK MAP kinases effectively prevented the IL-1beta effects. Inhibition of neutral sphingomyelinase, a key player in the IL-1beta signaling cascade that acts upstream of ERK, also suppressed the IL-1beta effects, while increasing the ceramide, through the addition of C2-ceramide or via treatment with exogenous sphingomyelinase, was sufficient to induce IGFBP1 promoter-driven luciferase activity. Studies in primary rat hepatocytes where the levels of neutral sphingomyelinase were either elevated or suppressed using adenoviral constructs affirmed the key role of neutral sphingomyelinase and ceramide (exerted likely through ERK activation) in the IL-1beta-induced IGFBP1 production. Finally, the IL-1beta effects on IGFBP1 mRNA production and protein secretion could be abolished by the addition of insulin, either at very late time points or at very high doses. PMID- 26884384 TI - Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet. AB - Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic beta-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic beta-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations. PMID- 26884385 TI - Regulation of cardiomyocyte autophagy by calcium. AB - Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy. PMID- 26884388 TI - Correction. PMID- 26884387 TI - Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity. AB - Sweet taste receptors (STRs) on the tongue mediate gustatory sweet sensing, but their expression in the gut, pancreas, and adipose tissue suggests a physiological contribution to whole body nutrient sensing and metabolism. However, little is known about the function and contribution of these sugar sensors during metabolic stress induced by overnutrition and subsequent obesity. Here, we investigated the effects of high-fat/low-carbohydrate (HF/LC) diet on glucose homeostasis and energy balance in mice with global disruption of the sweet taste receptor protein T1R2. We assessed body composition, energy balance, glucose homeostasis, and tissue-specific nutrient metabolism in T1R2 knockout (T1R2-KO) mice fed a HF/LC diet for 12 wk. HF/LC diet-fed T1R2-KO mice gained a similar amount of body mass as did WT mice, but had reduced fat mass and increased lean mass relative to WT mice. T1R2-KO mice were also hyperphagic and hyperactive. Ablation of the T1R2 sugar sensor protected mice from HF/LC diet induced hyperinsulinemia and altered substrate utilization, including increased rates of glucose oxidation and decreased liver triglyceride (TG) accumulation, despite normal intestinal fat absorption. Finally, STRs (T1r2/T1r3) were upregulated in the adipose tissue of WT mice in response to HF/LC diet, and their expression positively correlated with fat mass and glucose intolerance. The chemosensory receptor T1R2, plays an important role in glucose homeostasis during diet-induced obesity through the regulation of yet to be identified molecular mechanisms that alter energy disposal and utilization in peripheral tissues. PMID- 26884386 TI - Pulsatile delivery of a leucine supplement during long-term continuous enteral feeding enhances lean growth in term neonatal pigs. AB - Neonatal pigs are used as a model to study and optimize the clinical treatment of infants who are unable to maintain oral feeding. Using this model, we have shown previously that pulsatile administration of leucine during continuous feeding over 24 h via orogastric tube enhanced protein synthesis in skeletal muscle compared with continuous feeding alone. To determine the long-term effects of leucine pulses, neonatal piglets (n = 11-12/group) were continuously fed formula via orogastric tube for 21 days, with an additional parenteral infusion of either leucine (CON + LEU; 800 MUmol.kg-1.h-1) or alanine (CON + ALA) for 1 h every 4 h. The results show that body and muscle weights and lean gain were ~25% greater, and fat gain was 48% lower in CON + LEU than CON + ALA; weights of other tissues were unaffected by treatment. Fractional protein synthesis rates in longissimus dorsi, gastrocnemius, and soleus muscles were ~30% higher in CON + LEU compared with CON + ALA and were associated with decreased Deptor abundance and increased mTORC1, mTORC2, 4E-BP1, and S6K1 phosphorylation, SNAT2 abundance, and association of eIF4E with eIF4G and RagC with mTOR. There were no treatment effects on PKB, eIF2alpha, eEF2, or PRAS40 phosphorylation, Rheb, SLC38A9, v ATPase, LAMTOR1, LAMTOR2, RagA, RagC, and LAT1 abundance, the proportion of polysomes to nonpolysomes, or the proportion of mRNAs encoding rpS4 or rpS8 associated with polysomes. Our results demonstrate that pulsatile delivery of a leucine supplement during 21 days of continuous enteral feeding enhances lean growth by stimulating the mTORC1-dependent translation initiation pathway, leading to protein synthesis in skeletal muscle of neonates. PMID- 26884389 TI - In Situ Investigation of Peptide-Lipid Interaction Between PAP248-286 and Model Cell Membranes. AB - Sum frequency generation vibrational spectroscopy (SFG) was utilized to investigate the interaction between PAP248-286 and the two lipid bilayer systems. The present study also provides spectroscopic evidence to confirm that, although PAP248-286 is unable to penetrate into the hydrophobic core of the lipid bilayers, it is capable of interacting more intimately with the fluid-phase POPG/POPC than with the gel-phase DPPG/DPPC lipid bilayer. The helical structure content of lipid-bound PAP248-286 was also observed to be high, in contrast to the results previously reported using nuclear magnetic resonance (NMR). Collectively, our SFG data suggest that lipid-bound PAP248-286 actually resembles its structure in 50 % 2,2,2-trifluoroethanol better than the structure when the peptide binds to SDS micelles. This present study questions the use of SDS micelles as the model membrane for NMR studies of PAP248-286 due to its protein denaturing activity. PMID- 26884390 TI - Estimating the Time to Benefit for Preventive Drugs with the Statistical Process Control Method: An Example with Alendronate. AB - BACKGROUND: For physicians dealing with patients with a limited life expectancy, knowing the time to benefit (TTB) of preventive medication is essential to support treatment decisions. OBJECTIVE: The aim of this study was to investigate the usefulness of statistical process control (SPC) for determining the TTB in relation to fracture risk with alendronate versus placebo in postmenopausal women. METHODS: We performed a post hoc analysis of the Fracture Intervention Trial (FIT), a randomized, controlled trial that investigated the effect of alendronate versus placebo on fracture risk in postmenopausal women. We used SPC, a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. SPC discriminated between the normal variations over time in the numbers of fractures in both groups and the variations that were attributable to alendronate. The TTB was defined as the time point from which the cumulative difference in the number of clinical fractures remained greater than the upper control limit on the SPC chart. RESULTS: For the total group, the TTB was defined as 11 months. For patients aged >=70 years, the TTB was 8 months [absolute risk reduction (ARR) = 1.4%]; for patients aged <70 years, it was 19 months (ARR = 0.7%). CONCLUSION: SPC is a clear and understandable graphical method to determine the TTB. Its main advantage is that there is no need to define a prespecified time point, as is the case in traditional survival analyses. Prescribing alendronate to patients who are aged >=70 years is useful because the TTB shows that they will benefit after 8 months. Investigators should report the TTB to simplify clinical decision making. PMID- 26884391 TI - Development of Clinical Pharmacy in Switzerland: Involvement of Community Pharmacists in Care for Older Patients. AB - The role of the community pharmacist in primary care has been undergoing change in Switzerland in parallel to international developments: it has become more clinically and patient oriented. Special services of community pharmacists to older patients taking long-term or multiple medications, discharged from hospitals or experiencing cognitive impairment or disability have been developed. These services require more clinical knowledge and skills from community pharmacists and are based on, for example, 'simple or intermediate medication reviews' focused primarily to improve medication adherence and rational drug use by a patient. Reflecting the new role of community pharmacies, this article describes the current services provided by community pharmacies in Switzerland, e.g., 'polymedication check', 'weekly pill organizer', and 'services for chronic patients', as well as new Swiss educational and reimbursement systems supporting development of these services. In the international context, involvement of community pharmacists in patient-oriented care is growing. This review summarizes positive and negative experiences from implementation of community pharmacy services in Switzerland and provides examples for the development of such services in other countries. PMID- 26884393 TI - The Notch meeting: an odyssey from structure to function. AB - The Notch signaling pathway plays fundamental roles in diverse developmental processes. Studies of the basic biology of Notch function have provided insights into how its dysfunction contributes to multi-systemic diseases and cancer. In addition, our understanding of Notch signaling in maintaining stem/progenitor cell populations is revealing new avenues for rekindling regeneration. The Notch IX meeting, which was held in Athens, Greece in October 2015, brought together scientists working on different model systems and studying Notch signaling in various contexts. Here, we provide a summary of the key points that were presented at the meeting. Although we focus on the molecular mechanisms that determine Notch signaling and its role in development, we also cover talks describing roles for Notch in adulthood. Together, the talks revealed how interactions between adjacent cells mediated by Notch regulate development and physiology at multiple levels. PMID- 26884392 TI - Optimization of Geriatric Pharmacotherapy: Role of Multifaceted Cooperation in the Hospital Setting. AB - Because older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate pharmacotherapy in these patients. This narrative review describes approaches to improve pharmacotherapy in older people in the hospital setting. Screening to identify older patients at risk of drug-related problems and adverse drug reactions (ADRs) is the first critical step within a multistep approach to geriatric pharmacotherapy. Two methods that have been developed are the GerontoNet ADR risk score and the Brighton Adverse Drug Reactions Risk (BADRI) model, which take into account a number of factors, the most important of which is the number of medicines. In order to reduce potentially inappropriate prescribing in older patients, different types of interventions exist, such as pharmacist-led medication reviews, educational interventions, computerized decision support systems, and comprehensive geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach, by combining different techniques. None of the existing interventions shows a clear beneficial effect on patients' health outcomes if applied in isolation; however, when these interventions are combined within the context of a multidisciplinary team, positive effects on patients' health outcomes can be expected. Appropriate geriatric pharmacotherapy, global assessment of patients' clinical and functional parameters, and integration of skills from different healthcare professionals are needed to address medical complexity of older adults. PMID- 26884395 TI - Endothelial cell-derived semaphorin 3A inhibits filopodia formation by blood vascular tip cells. AB - Vascular endothelial growth factor (VEGF)-A is a well-known major chemoattractant driver of angiogenesis--the formation of new blood vessels from pre-existing ones. However, the repellent factors that fine-tune this angiogenic process remain poorly characterized. We investigated the expression and functional role of endothelial cell-derived semaphorin 3A (Sema3A) in retinal angiogenesis, using genetic mouse models. We found Sema3a mRNA expression in the ganglion cell layer and the presence of Sema3A protein on larger blood vessels and at the growing front of blood vessels in neonatal retinas. The Sema3A receptors neuropilin-1 and plexin-A1 were expressed by retinal blood vessels. To study the endothelial cell specific role of Sema3A, we generated endothelial cell-specific Sema3A knockout mouse strains by constitutive or inducible vascular endothelial cadherin-Cre mediated gene disruption. We found that in neonatal retinas of these mice, both the number and the length of tip cell filopodia were significantly increased and the leading edge growth pattern was irregular. Retinal explant experiments showed that recombinant Sema3A significantly decreased VEGF-A-induced filopodia formation. Endothelial cell-specific knockout of Sema3A had no impact on blood vessel density or skin vascular leakage in adult mice. These findings indicate that endothelial cell-derived Sema3A exerts repelling functions on VEGF-A-induced tip cell filopodia and that a lack of this signaling cannot be rescued by paracrine sources of Sema3A. PMID- 26884394 TI - Stomach development, stem cells and disease. AB - The stomach, an organ derived from foregut endoderm, secretes acid and enzymes and plays a key role in digestion. During development, mesenchymal-epithelial interactions drive stomach specification, patterning, differentiation and growth through selected signaling pathways and transcription factors. After birth, the gastric epithelium is maintained by the activity of stem cells. Developmental signals are aberrantly activated and stem cell functions are disrupted in gastric cancer and other disorders. Therefore, a better understanding of stomach development and stem cells can inform approaches to treating these conditions. This Review highlights the molecular mechanisms of stomach development and discusses recent findings regarding stomach stem cells and organoid cultures, and their roles in investigating disease mechanisms. PMID- 26884398 TI - Inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling mediates delayed myogenesis in Duchenne muscular dystrophy fetal muscle. AB - Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder characterized by muscle wasting and premature death. The defective gene is dystrophin, a structural protein, absence of which causes membrane fragility and myofiber necrosis. Several lines of evidence showed that in adult DMD patients dystrophin is involved in signaling pathways that regulate calcium homeostasis and differentiation programs. However, secondary aspects of the disease, such as inflammation and fibrosis development, might represent a bias in the analysis. Because fetal muscle is not influenced by gravity and does not suffer from mechanical load and/or inflammation, we investigated 12-week-old fetal DMD skeletal muscles, highlighting for the first time early alterations in signaling pathways mediated by the absence of dystrophin itself. We found that PLC/IP3/IP3R/Ryr1/Ca(2+) signaling is widely active in fetal DMD skeletal muscles and, through the calcium-dependent PKCalpha protein, exerts a fundamental regulatory role in delaying myogenesis and in myofiber commitment. These data provide new insights into the origin of DMD pathology during muscle development. PMID- 26884397 TI - Cannabinoid receptor signaling regulates liver development and metabolism. AB - Endocannabinoid (EC) signaling mediates psychotropic effects and regulates appetite. By contrast, potential roles in organ development and embryonic energy consumption remain unknown. Here, we demonstrate that genetic or chemical inhibition of cannabinoid receptor (Cnr) activity disrupts liver development and metabolic function in zebrafish (Danio rerio), impacting hepatic differentiation, but not endodermal specification: loss of cannabinoid receptor 1 (cnr1) and cnr2 activity leads to smaller livers with fewer hepatocytes, reduced liver-specific gene expression and proliferation. Functional assays reveal abnormal biliary anatomy and lipid handling. Adult cnr2 mutants are susceptible to hepatic steatosis. Metabolomic analysis reveals reduced methionine content in Cnr mutants. Methionine supplementation rescues developmental and metabolic defects in Cnr mutant livers, suggesting a causal relationship between EC signaling, methionine deficiency and impaired liver development. The effect of Cnr on methionine metabolism is regulated by sterol regulatory element-binding transcription factors (Srebfs), as their overexpression rescues Cnr mutant liver phenotypes in a methionine-dependent manner. Our work describes a novel developmental role for EC signaling, whereby Cnr-mediated regulation of Srebfs and methionine metabolism impacts liver development and function. PMID- 26884396 TI - Differential regulation of mouse and human nephron progenitors by the Six family of transcriptional regulators. AB - Nephron endowment is determined by the self-renewal and induction of a nephron progenitor pool established at the onset of kidney development. In the mouse, the related transcriptional regulators Six1 and Six2 play non-overlapping roles in nephron progenitors. Transient Six1 activity prefigures, and is essential for, active nephrogenesis. By contrast, Six2 maintains later progenitor self-renewal from the onset of nephrogenesis. We compared the regulatory actions of Six2 in mouse and human nephron progenitors by chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq). Surprisingly, SIX1 was identified as a SIX2 target unique to the human nephron progenitors. Furthermore, RNA-seq and immunostaining revealed overlapping SIX1 and SIX2 activity in 16 week human fetal nephron progenitors. Comparative bioinformatic analysis of human SIX1 and SIX2 ChIP-seq showed each factor targeted a similar set of cis-regulatory modules binding an identical target recognition motif. In contrast to the mouse where Six2 binds its own enhancers but does not interact with DNA around Six1, both human SIX1 and SIX2 bind homologous SIX2 enhancers and putative enhancers positioned around SIX1. Transgenic analysis of a putative human SIX1 enhancer in the mouse revealed a transient, mouse-like, pre-nephrogenic, Six1 regulatory pattern. Together, these data demonstrate a divergence in SIX-factor regulation between mouse and human nephron progenitors. In the human, an auto/cross-regulatory loop drives continued SIX1 and SIX2 expression during active nephrogenesis. By contrast, the mouse establishes only an auto-regulatory Six2 loop. These data suggest differential SIX-factor regulation might have contributed to species differences in nephron progenitor programs such as the duration of nephrogenesis and the final nephron count. PMID- 26884400 TI - The classification of frontal sinus pneumatization patterns by CT-based volumetry. AB - PURPOSE: We aimed to define the classification of frontal sinus pneumatization patterns according to three-dimensional volume measurements. METHODS: Datasets of 148 sides of 74 dry skulls were generated by the computerized tomography-based volumetry to measure frontal sinus volumes. The cutoff points for frontal sinus hypoplasia and hyperplasia were tested by ROC curve analysis and the validity of the diagnostic points was measured. RESULTS: The overall frequencies were 4.1, 14.2, 37.2 and 44.5 % for frontal sinus aplasia, hypoplasia, medium size and hyperplasia, respectively. The aplasia was bilateral in all three skulls. Hypoplasia was seen 76 % at the right side and hyperplasia was seen 56 % at the left side. The cutoff points for diagnosing frontal sinus hypoplasia and hyperplasia were '1131.25 mm(3)' (95.2 % sensitivity and 100 % specificity) and '3328.50 mm(3)' (88 % sensitivity and 86 % specificity), respectively. CONCLUSIONS: The findings provided in the present study, which define frontal sinus pneumatization patterns by CT-based volumetry, proved that two opposite sides of the frontal sinuses are asymmetric and three-dimensional classification should be developed by CT-based volumetry, because two-dimensional evaluations lack depth measurement. PMID- 26884399 TI - Molecular model for force production and transmission during vertebrate gastrulation. AB - Vertebrate embryos undergo dramatic shape changes at gastrulation that require locally produced and anisotropically applied forces, yet how these forces are produced and transmitted across tissues remains unclear. We show that depletion of myosin regulatory light chain (RLC) levels in the embryo blocks force generation at gastrulation through two distinct mechanisms: destabilizing the myosin II (MII) hexameric complex and inhibiting MII contractility. Molecular dissection of these two mechanisms demonstrates that normal convergence force generation requires MII contractility and we identify a set of molecular phenotypes correlated with both this failure of convergence force generation in explants and of blastopore closure in whole embryos. These include reduced rates of actin movement, alterations in C-cadherin dynamics and a reduction in the number of polarized lamellipodia on intercalating cells. By examining the spatial relationship between C-cadherin and actomyosin we also find evidence for formation of transcellular linear arrays incorporating these proteins that could transmit mediolaterally oriented tensional forces. These data combine to suggest a multistep model to explain how cell intercalation can occur against a force gradient to generate axial extension forces. First, polarized lamellipodia extend mediolaterally and make new C-cadherin-based contacts with neighboring mesodermal cell bodies. Second, lamellipodial flow of actin coalesces into a tension bearing, MII-contractility-dependent node-and-cable actin network in the cell body cortex. And third, this actomyosin network contracts to generate mediolateral convergence forces in the context of these transcellular arrays. PMID- 26884401 TI - Nucleating emergency radiology specialization in India. AB - Emergency radiology is being recognized as an important and distinct specialty of radiology which merits utmost attention of educators, radiology program curricula committees, and radiology practices in India. Providing an accurate but timely diagnosis requires a skilled judgement and a strong process framework, particularly in acute trauma setting or a life-threatening acute illness. However, due to a shortage of radiologists in India and lack of awareness and suitable opportunities, there has been no concerted movement towards emergency radiology subspecialty training or dedicated emergency radiology positions. It was with these gaps in mind that the Society for Emergency Radiology was envisioned in 2012 and formulated in 2013. The proposed role of the Society for Emergency Radiology is to identify deficiencies in the field, namely, lack of adequate exposure, lack of mentorship by experienced emergency radiologists, lack of suitable opportunities for emergency radiologists; establish standards of practice; and promote education and implementation research to bridge the gaps. Through collaboration with other societies and partnership with the journal Emergency Radiology, the Society for Emergency Radiology hopes to promote a free exchange of ideas, protocols, and multi-institutional trials across continents. PMID- 26884402 TI - Core curriculum illustration: necrotizing pneumonia and empyema. AB - This is the 18th installment of a series that will highlight one case per publication issue from the bank of cases available online as part of the American Society of Emergency Radiology (ASER) educational resources. Our goal is to generate more interest in and use of our online materials. To view more cases online please visit the ASER Core Curriculum and Recommendations for Study online at: http://www.erad.org/?page=CCIP_TOC . PMID- 26884403 TI - Highlights from the scientific and educational abstracts presented at the ASER 2015 annual scientific meeting and postgraduate course. AB - The American Society of Emergency Radiology (ASER) 2015 Annual Scientific Meeting and Postgraduate Course offered dedicated learning sessions, oral presentations, and digital exhibits on a broad spectrum of topics in emergency radiology, including traumatic and non-traumatic emergencies, quality, communication, education, technological innovations, and the evolving identity of the emergency radiology subspecialty. This article highlights the scientific and educational abstracts presented at the meeting. PMID- 26884404 TI - Subregional Expression of Hippocampal Glutamatergic and GABAergic Genes in F344 Rats with Social Isolation after Weaning. AB - Many studies have shown that postweaning social isolation (pwSI) alters various behavioral phenotypes, including hippocampusdependent tasks. Here, we report the comprehensive analysis of the expression of glutamatergic and GABAergic neurotransmissionrelated genes in the distinct hippocampal subregions of pwSI rats. Male F344 rats (age, 4 wk) experienced either pwSI or group housing (controls). At 7 wk of age, the hippocampus of each rat was removed and laser microdissected into the CA1 and CA3 layers of pyramidal cells and the granule cell layer of the dentate gyrus. Subsequently, the expression of glutamatergic- and GABAergic- related genes was analyzed by quantitative RT-PCR. In the CA1 and CA3 pyramidal cell layers, 18 of 24 glutamate receptor subunit genes were at least 1.5-fold increased in expression after pwSI. In particular, the expression of several N-methyl-D-aspartate and kainate receptors (for example, Grin2a in CA1, Grik4 in CA3) was significantly increased after pwSI. In contrast, pwSI tended to decrease the expression of GABAA receptor subunit genes, and Gabra1, Gabra2, Gabra4, Gabra5, Gabrb2, Gabrg1, and Gabrg2 were all significantly decreased in expression compared with the levels in the group-housed rats. These results indicate a subregion- specific increase of glutamate receptors and reduction of GABAA receptors, suggesting that the hippocampal circuits of pwSI rats may be in more excitable states than those of group-housed rats. PMID- 26884406 TI - Collagenoma in an African Clawed Frog (Xenopus laevis). AB - A 3-y-old female Xenopus laevis was reported for a gray mass on the abdomen. The frog was used for egg collection and was otherwise experimentally naive. On physical exam, the frog was bright and active and had a firm, gray, lobulated mass (1.5 cm * 0.5 cm * 0.5 cm) in the cutaneous tissue of the left lateral abdomen. An excisional biopsy was performed under anesthesia, and the entire mass was removed and processed for histopathology. Microscopically, the dermis was greatly expanded by connective tissue with a marked decrease in the number of glands, and occasional degenerative glands were present. When stained with Masson trichrome, the excessive connective tissue stained blue, indicating that it was composed of collagen. With Verhoeff-van Gieson staining, the connective tissue stained bright red with an absence of black-staining material, demonstrating the presence of collagen and ruling out elastic fibers. In light of the morphology of the mass and the results of the special stains, the mass was diagnosed as a collagenoma. To our knowledge, this report is the first description of a collagenoma in X. laevis. PMID- 26884405 TI - Renal Function and Hematology in Rats with Congenital Renal Hypoplasia. AB - Renal hypoplasia due to a congenitally reduced number of nephrons progresses to chronic kidney disease and may cause renal anemia, given that the kidneys are a major source of erythropoietin in adults. Hypoplastic kidney (HPK) rats have only about 20% of the normal number of nephrons and develop CKD. This study assessed the renal function and hematologic changes in HPK rats from 70 to 210 d of age. HPK rats demonstrated deterioration of renal excretory function, slightly macrocytic erythropenia at all days examined, age-related increases in splenic hemosiderosis accompanied by a tendency toward increased hemolysis, normal plasma erythropoietin levels associated with increased hepatic and decreased renal erythropoietin production, and maintenance of the response for erythropoietin production to hypoxic conditions, with increased interstitial fibrosis at 140 d of age. These results indicate that increases in splenic hemosiderosis and the membrane fragility of RBC might be associated with erythropenia and that hepatic production of erythropoietin might contribute to maintaining the blood Hgb concentration in HPK rats. PMID- 26884407 TI - Effect of Gonadectomy on the Androgen-Dependent Behavior of Ganglion Cell-Like Cells in Djungarian Hamsters (Phodopus sungorus). AB - Ganglion cell-like (GL) cells reside in the dermis of the ventral skin of mature male Djungarian hamsters (Phodopus sugorus) and express androgen receptor (AR). To assess whether GL cells have androgen-dependent behavior, we evaluated the histologic changes of GL cells after gonadectomy. Five male and 5 female hamsters were gonadectomized at the age of 4 wk and necropsied 14 wk later. The number, distribution, and proliferative activity of GL cells in the thoracoabdominal and dorsal skins were evaluated histologically and compared with those of corresponding intact animals. GL cells were more numerous, were distributed throughout the skin more widely, and had higher proliferative activity in the intact male hamsters than in their gonadectomized counterparts. Similar trends regarding these 3 parameters were seen in ovariectomized compared with intact female hamsters and between intact male and intact female hamsters. These results suggest that the GL cells of Djungarian hamsters demonstrate sex-associated differences in their distribution and proliferative activity and that androgen may be involved in the development of these cells. PMID- 26884408 TI - Analysis of Gene Expression and Ultrastructure of Stifle Menisci from Juvenile and Adult Pigs. AB - The origin of the age-associated degenerative processes in meniscal tissue is poorly understood and may be related to an imbalance of anabolic and catabolic metabolism. The aim of the current study was to compare medial menisci isolated from juvenile pigs and degenerated medial menisci from adult pigs in terms of gene expression profile and ultrastructure. Medial menisci were isolated from the knee joints of juvenile and adult pigs (n = 8 for each group). Degeneration was determined histologically according to a scoring system. In addition, the gene expression profiles of 14 genes encoding extracellular matrix proteins, catabolic matrix metalloproteinases and mediators of inflammation were analyzed. Changes in the ultrastructure of the collagen network of the meniscal tissue were analyzed by using transmission electron microscopy. The histologic analysis of menisci showed significantly higher grade of degeneration in tissue isolated from adult porcine knee joints compared with menisci isolated from juvenile knee joints. In particular, destruction of the collagen network was greater in adult menisci than in juvenile menisci. Degenerated menisci showed significantly decreased gene expression of COL1A1 and increased expression of MMP2, MMP13, and IL8. The menisci from adult porcine knee joints can serve as a model for meniscal degeneration. Degenerative changes were manifested as differences in histopathology, gene expression and ultrastructure of collagen network. PMID- 26884409 TI - Natural Progression of Canine Glycogen Storage Disease Type IIIa. AB - Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies. PMID- 26884410 TI - Use of an Implantable Loop Recorder in a Chimpanzee (Pan troglodytes) to Monitor Cardiac Arrhythmias and Assess the Effects of Acupuncture and Laser Therapy. AB - Cardiovascular disease is a leading cause of death in captive chimpanzees and is often associated with myocardial fibrosis, which increases the risk of cardiac arrhythmias. In this case report, we present a 36-y-old male chimpanzee (Pan troglodytes) diagnosed with frequent ventricular premature complexes (VPC). We placed a subcutaneous implantable loop recorder for continual ECG monitoring to assess his arrhythmias without the confounding effects of anesthetics. During his initial treatment with the antiarrhythmia medication amiodarone, he developed thrombocytopenia, and the drug was discontinued. After reviewing other potential therapies for the treatment of cardiac arrhythmias, we elected to try acupuncture and laser therapy in view of the positive results and the lack of adverse side effects reported in humans. We used 2 well-known cardiac acupuncture sites on the wrist, PC6 (pericardium 6) and HT7 (heart 7), and evaluated the results of the therapy by using the ECG recordings from the implantable loop recorder. Although periodic increases in the animal's excitement level introduced confounding variables that caused some variation in the data, acupuncture and laser therapy appeared to decrease the mean number of VPC/min in this chimpanzee. PMID- 26884411 TI - Granuloma Due to Oxidized Regenerated Cellulose in an Aged Rhesus Macaque (Macaca mulatta). AB - Bioabsorbable hemostatic agents such as oxidized regenerated cellulose are widely used to control intraoperative diffuse capillary bleeding. Compared with electrocautery or ligation, oxidized regenerated cellulose has the advantage of controlling bleeding without occluding the vessel lumen or causing thermal injuries to adjacent tissue. Although the manufacturer recommends removal of the material once hemostasis is achieved, oxidized regenerated cellulose is a bioabsorbable hemostatic agent and is often left in the surgical bed to prevent subsequent bleeding after surgical closure. However, noninvasive imaging techniques have revealed granulomatous foreign-body reactions that mimic infection or tumor recurrence. We present a case report of sterile peritonitis and granuloma formation secondary to the presence of oxidized regenerated cellulose after intestinal resection to excise a colonic adenocarcinoma in an aged rhesus macaque. PMID- 26884412 TI - Spontaneous Cholelithiasis in a Squirrel Monkey (Saimiri sciureus). AB - A mature female squirrel monkey was noted during routine semiannual examinations to have moderate progressive weight loss. Serum chemistry panels revealed marked increases in hepatic enzyme, bilirubin, and bile salt concentrations and hypoalbuminemia. Abdominal ultrasonography revealed echogenic, shadowing debris in the gallbladder, consistent with cholelithiasis. At necropsy, marked thickening and distension of the gallbladder, cystic duct, and common bile duct was noted, and more than 50 irregularly shaped, black gallstones were removed from the biliary tract. Gallbladder tissue, bile, and gallstones cultured positive for Escherichia coli and Proteus spp., suggesting a brown-pigment gallstone type secondary to a bacterial nidus. Histopathology revealed severe chronic-active diffuse cholecystitis and severe chronic-active hepatic degeneration and necrosis with severe cholestasis. To our knowledge, this report is the first description of spontaneous choleilthiasis in a squirrel monkey. PMID- 26884413 TI - Asthma in an Adult Female Vervet Monkey (Chlorocebus sabaeus). AB - A 9-y-old, colony-bred, female vervet monkey (Chlorocebus sabaeus) presented with a 6-y history of open-mouth breathing, tachypnea, and sibilant wheezing. These symptoms did not significantly affect her activity or quality of life. Thoracic radiographs and results of bronchoalveolar lavage supported the diagnosis of asthma. Treatment comprising intramuscular prednisolone (tapered over 2 mo from twice daily to every other day), inhaled salmeterol-fluticasone (25 MUg-250 MUg per actuation twice daily) by mask, and a metered dose inhaler was successful in restoring a normal respiratory pattern. Despite the availability of several primate models of human asthma, this case represents the first report of spontaneous asthma in a NHP. PMID- 26884417 TI - Hypopigmentation of newborn skin. PMID- 26884414 TI - The role of respiratory viruses in the etiology of bacterial pneumonia: An ecological perspective. AB - Pneumonia is the leading cause of death among children less than 5 years old worldwide. A wide range of viral, bacterial and fungal agents can cause pneumonia: although viruses are the most common etiologic agent, the severity of clinical symptoms associated with bacterial pneumonia and increasing antibiotic resistance makes bacterial pneumonia a major public health concern. Bacterial pneumonia can follow upper respiratory viral infection and complicate lower respiratory viral infection. Secondary bacterial pneumonia is a major cause of influenza-related deaths. In this review, we evaluate the following hypotheses: (i) respiratory viruses influence the etiology of pneumonia by altering bacterial community structure in the upper respiratory tract (URT) and (ii) respiratory viruses promote or inhibit colonization of the lower respiratory tract (LRT) by certain bacterial species residing in the URT. We conducted a systematic review of the literature to examine temporal associations between respiratory viruses and bacteria and a targeted review to identify potential mechanisms of interactions. We conclude that viruses both alter the bacterial community in the URT and promote bacterial colonization of the LRT. However, it is uncertain whether changes in the URT bacterial community play a substantial role in pneumonia etiology. The exception is Streptococcus pneumoniae where a strong link between viral co-infection, increased carriage and pneumococcal pneumonia has been established. PMID- 26884415 TI - Predicting global variation in infectious disease severity: A bottom-up approach. AB - BACKGROUND AND OBJECTIVES: Understanding the underlying causes for the variation in case-fatality-ratios (CFR) is important for assessing the mechanism governing global disparity in the burden of infectious diseases. Variation in CFR is likely to be driven by factors such as population genetics, demography, transmission patterns and general health status. We present data here that support the hypothsis that changes in CFRs for specific diseases may be the result of serial passage through different hosts. For example passage through adults may lead to lower CFR, whereas passage through children may have the opposite effect. Accordingly changes in CFR may occur in parallel with demographic transitions. METHODOLOGY: We explored the predictability of CFR using data obtained from the World Health Organization (WHO) disease databases for four human diseases: mumps, malaria, tuberculosis and leptospirosis and assessed these for association with a range of population characteristics, such as crude birth and death rates, median age of the population, mean body mass index, proportion living in urban areas and tuberculosis vaccine coverage. We then tested this predictive model on Danish historical demographic and population data. RESULTS: Birth rates were the best predictor for mumps and malaria CFR. For tuberculosis CFR death rates were the best predictor and for leptospirosis population density was a significant predictor. CONCLUSIONS AND IMPLICATIONS: CFR predictors differed among diseases according to their biology. We suggest that the overall result reflects an interaction between the forces driving demographic change and the virulence of human-to-human transmitted diseases. PMID- 26884416 TI - Explaining the sex difference in depression with a unified bargaining model of anger and depression. AB - BACKGROUND: Women are twice as likely as men to be depressed, a bias that is poorly understood. One evolutionary model proposes that depression is a bargaining strategy to compel reluctant social partners to provide more help in the wake of adversity. An evolutionary model of anger proposes that high upper body strength predisposes individuals to angrily threaten social partners who offer too few benefits or impose too many costs. Here, we propose that when social partners provide too few benefits or impose too many costs, the physically strong become overtly angry and the physically weak become depressed. The sexual dimorphism in upper body strength means that men will be more likely to bargain with anger and physical threats and women with depression. METHODOLOGY: We tested this idea using the 2011-12 National Health and Nutrition Examination Survey (NHANES), a large nationally representative sample of US households that included measures of depression and upper body strength. RESULTS: A 2 SD increase in grip strength decreased the odds of depression by more than half ([Formula: see text],[Formula: see text]), which did not appear to be a consequence of confounds with anthropometric, hormonal or socioeconomic variables, but was partially explained by a confound with physical disability. Nevertheless, upper body strength mediated 63% of the effect of sex on depression, but the mediation effect was unexpectedly moderated by age. CONCLUSIONS: Low upper body strength is a risk factor for depression, especially in older adults, and the sex difference in body strength appears to explain much of the perplexing sex difference in depression. PMID- 26884418 TI - The role of anti-phospholipid antibodies in autoimmune reproductive failure. AB - Anti-phospholipid antibodies (aPL) are autoantibodies that are associated with thrombosis and a range of pregnancy complications including recurrent pregnancy loss and pre-eclampsia. The three clinically relevant, well-characterized aPL are anti-cardiolipin antibodies, lupus anticoagulant and anti-beta-2-glycoprotein I (beta2GPI) antibodies. aPL do not bind directly to phospholipids but instead bind to a plasma-binding 'cofactor'. The most extensively studied cofactor is beta2GPI, whose role in pregnancy is not fully elucidated. Although the pathogenicity of aPL in recurrent pregnancy loss is well established in humans and animal models, the association of aPL with infertility does not appear to be causative. aPL may exert their detrimental effects during pregnancy by directly binding trophoblast cells of the placenta, altering trophoblast signalling, proliferation, invasion and secretion of hormones and cytokines, and by increasing apoptosis. Heparin is commonly used to treat pregnant women with aPL; however, as thrombotic events do not occur in the placentae of all women with aPL, it may exert a protective effect by preventing the binding of aPL to beta2GPI or by acting through non-thrombotic pathways. The aim of this review is to present evidence summarizing the current understanding of this field. PMID- 26884419 TI - On the origin of sperm epigenetic heterogeneity. AB - The influence of epigenetic modifications on reproduction and on the function of male germ cells has been thoroughly demonstrated. In particular, aberrant DNA methylation levels in sperm have been associated with abnormal sperm parameters, lower fertilization rates and impaired embryo development. Recent reports have indicated that human sperm might be epigenetically heterogeneous and that abnormal DNA methylation levels found in the sperm of infertile men could be due to the presence of sperm populations with different epigenetic quality. However, the origin and the contribution of different germ cell types to this suspected heterogeneity remain unclear. In this review, we focus on sperm epigenetics at the DNA methylation level and its importance in reproduction. We take into account the latest developments and hypotheses concerning the functional significance of epigenetic heterogeneity coming from the field of stem cell and cancer biology and discuss the potential importance and consequences of sperm epigenetic heterogeneity for reproduction, male (in)fertility and assisted reproductive technologies (ART). Based on the current information, we propose a model in which spermatogonial stem cell variability, either intrinsic or due to external factors (such as endocrine action and environmental stimuli), can lead to epigenetic sperm heterogeneity, sperm epimutations and male infertility. The elucidation of the precise causes for epimutations, the conception of adequate therapeutic options and the development of sperm selection technologies based on epigenetic quality should be regarded as crucial to the improvement of ART outcome in the near future. PMID- 26884420 TI - Concerns about study on maternal H1N1 influenza vaccination and offspring mortality. PMID- 26884421 TI - Sleep bruxism in adolescents: a systematic literature review of related risk factors. AB - BACKGROUND: Multiple risk factors have been associated to sleep bruxism (SB). Nevertheless, there are still many unsolved issues concerning the etiology of SB that have consequences on the clinical management strategies. OBJECTIVE: Systematically review the literature to assess the relationship between risk factors and SB symptoms in adolescents (age 11-19 years). SEARCH METHODS AND SELECTION CRITERIA: PubMed, Embase, Scopus, Cochrane Oral Health Group's Trial Register and Cochrane Register of Controlled Trials, Web of Science, LILACs, and SciELO were searched to identify all peer-reviewed articles potentially relevant to the review. DATA COLLECTION AND ANALYSIS: The risk of bias was assessed according to the guidelines from the Cochrane handbook for systematic reviews of interventions, with reporting in agreement to the preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Four out of the 4546 initially identified articles were selected. According to the grading of recommendations assessment, development and evaluation assessment (GRADE), the magnitude of agreement was almost perfect for all checklist items. Sleep disturbances, and snoring in particular, headache, jaw muscle fatigue, and tooth wear seem to be associated to SB in adolescents from 11 to 19 years old. LIMITATIONS: Despite the large interest of the scientific community in the field of oral parafunctions, only four articles met the eligibility criteria. Furthermore only associations and not definite cause-effect relationships were highlighted in the selected articles. CONCLUSIONS: Sleep disturbances presented the strongest association with SB while very few occlusal features had a moderate association. As a common sense the investigation of sleep respiratory disorders could be of great help in the management of SB in adolescents. PMID- 26884422 TI - Unblinded CGM Should Replace Blinded CGM in the Clinical Management of Diabetes. AB - The original continuous glucose monitors (CGMs) were limited to 3-day, blinded observation periods where glucose data was hidden from patients and later retrospectively analyzed by a provider to help guide the management of diabetes. Unblinded CGM, released several years later, allows patients to view their glucose data in real-time amidst their daily routines, enabling them to better understand how variables such as activity, nutrition, and medications affect glucose levels. Research studies consistently demonstrate improved glycemic control and reduced hypoglycemia in children and adults with type 1 and type 2 diabetes while using unblinded CGM.(1-4) As such, we believe that all CGM usage in clinical practice should be in real-time, unblinded mode for short-term and long-term wear periods. PMID- 26884423 TI - Authors' reply to Amitai and Koren. PMID- 26884424 TI - Digging deeper into the intronic sequences of the SPINK1 gene. PMID- 26884425 TI - Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. AB - OBJECTIVE: The influence of eosinophilic oesophagitis (EoE)-associated inflammation upon oesophageal epithelial biology remains poorly understood. We investigated the functional role of autophagy in oesophageal epithelial cells (keratinocytes) exposed to the inflammatory EoE milieu. DESIGN: Functional consequences of genetic or pharmacological autophagy inhibition were assessed in endoscopic oesophageal biopsies, human oesophageal keratinocytes, single cell derived ex vivo murine oesophageal organoids as well as a murine model recapitulating EoE-like inflammation and basal cell hyperplasia. Gene expression, morphological and functional characterisation of autophagy and oxidative stress were performed by transmission electron microscopy, immunostaining, immunoblotting, live cell imaging and flow cytometry. RESULTS: EoE-relevant inflammatory conditions promoted autophagy and basal cell hyperplasia in three independent murine EoE models and oesophageal organoids. Inhibition of autophagic flux via chloroquine treatment augmented basal cell hyperplasia in these model systems. Oesophageal keratinocytes stimulated with EoE-relevant cytokines, including tumour necrosis factor-alpha and interleukin-13 exhibited activation of autophagic flux in a reactive oxygen species-dependent manner. Autophagy inhibition via chloroquine treatment or depletion of Beclin-1 or ATG-7, augmented oxidative stress induced by EoE-relevant stimuli in murine EoE, oesophageal organoids and human oesophageal keratinocytes. Oesophageal epithelia of paediatric EoE patients with active inflammation displayed increased autophagic vesicle content compared with normal and EoE remission subjects. Functional flow cytometric analysis revealed autophagic flux in human oesophageal biopsies. CONCLUSIONS: Our findings reveal for the first time that autophagy may function as a cytoprotective mechanism to maintain epithelial redox balance and homeostasis under EoE inflammation-associated stress, providing mechanistic insights into the role of autophagy in EoE pathogenesis. PMID- 26884426 TI - Quantitative evaluation of human bone mesenchymal stem cells rescuing fulminant hepatic failure in pigs. AB - OBJECTIVE: Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells' activities. Our objective was to clarify stem cell recipient interactions for overcoming barriers to clinical application. DESIGN: We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells' activities. The control and transplantation groups of pigs (n=15 per group) both received a D galactosamine (D-Gal) injection (1.5 g/kg). The transplantation group received hBMSCs via intraportal vein infusion (3*106 cells/kg) immediately after D-Gal administration. The stem cell-recipient interactions were quantitatively evaluated by biochemical function, cytokine array, metabolite profiling, transcriptome sequencing and immunohistochemistry. RESULTS: All pigs in the control group died within an average of 3.22 days, whereas 13/15 pigs in the transplantation group lived >14 days. The cytokine array and metabolite profiling analyses revealed that hBMSC transplantation suppressed D-Gal-induced life threatening cytokine storms and stabilised FHF within 7 days, while human-derived hepatocytes constituted only ~4.5% of the pig hepatocytes. The functional synergy analysis of the observed profile changes indicated that the implanted hBMSCs altered the pigs' cytokine responses to damage through paracrine effects. Delta like ligand 4 was validated to assist liver restoration in both pig and rat FHF models. CONCLUSIONS: Our results delineated an integrated model of the multifaceted interactions between stem cells and recipients, which may open a new avenue to the discovery of single molecule-based therapeutics that simulate stem cell actions. PMID- 26884427 TI - Intestinal Long-Chain Fatty Acids Act as a Direct Signal To Modulate Expression of the Salmonella Pathogenicity Island 1 Type III Secretion System. AB - Salmonella enterica serovar Typhimurium uses the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS) to induce inflammatory diarrhea and bacterial uptake into intestinal epithelial cells. The expression of hilA, encoding the transcriptional activator of the T3SS structural genes, is directly controlled by three AraC-like regulators, HilD, HilC, and RtsA, each of which can activate hilD, hilC, rtsA, and hilA genes, forming a complex feed-forward regulatory loop. Expression of the SPI1 genes is tightly controlled by numerous regulatory inputs to ensure proper timing in production of the T3SS apparatus. Loss of FadD, an acyl coenzyme A (acyl-CoA) synthetase required for degradation of long-chain fatty acids (LCFAs), was known to decrease hilA expression. We show that free external LCFAs repress expression of hilA independently of FadD and the LCFA degradation pathway. Genetic and biochemical evidence suggests that LCFAs act directly to block primarily HilD activity. Further analyses show that in the absence of FadD, hilA expression is downregulated due to endogenous production of free LCFAs, which are excreted into the culture medium via TolC and then transported back into the bacterial cell via FadL. A fadL mutant is more virulent than the wild-type strain in mouse oral competition assays independently of LCFA degradation, showing that, in the host, dietary LCFAs serve as a signal for proper regulation of SPI1 expression, rather than an energy source. IMPORTANCE: To cause disease, Salmonella must respond to diverse environmental cues to express its invasion machinery at the appropriate location in the host intestine. We show that host intestinal free long-chain fatty acids (LCFAs) affect Salmonella invasion by reducing expression of the SPI1 type III secretion system, acting primarily via the AraC-like activator HilD. Degradation of LCFAs is not required for this regulation, showing that free LCFAs serve as a cue to proper intestinal localization to invade host epithelial cells and not as a nutrient source. PMID- 26884429 TI - Hidden Staphylococcus aureus Carriage: Overrated or Underappreciated? AB - Staphylococcus aureus is a persistent companion bacterial species in one-third of humankind. Reservoirs include the nasal and nasopharyngeal cavities, skin, and gastrointestinal (GI) tract. Despite earlier claims that colonization of individuals is caused by clonal organisms, next-generation sequencing (NGS) has revealed that resident type heterogeneity is not exceptional. Carriage, whether overt or hidden, is correlated with a risk of autoinfection. In a recent article in mBio, it was shown that, based on staphylococcal genome sequencing, low-level GI persistence may cause long-term nosocomial outbreaks [L. Senn et al., 7(1):e02039-15, 2016, doi:10.1128/mBio.02039-15]. Institutional endemicity with methicillin-resistant S. aureus (MRSA) sequence type 228 (ST228) is shown to originate not from high-level nasal carriage or poor compliance with infection control practice but from low-grade asymptomatic GI colonization. This shows the power of NGS in elucidating staphylococcal epidemiology and, even more important, demonstrates that (drug-resistant) microorganisms may possess stealthy means of persistence. Identifying these persistence mechanisms is key to successful infection control. PMID- 26884428 TI - Demography and Intercontinental Spread of the USA300 Community-Acquired Methicillin-Resistant Staphylococcus aureus Lineage. AB - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized worldwide during the 1990s; in less than a decade, several genetically distinct CA-MRSA lineages carrying Panton-Valentine leukocidin genes have emerged on every continent. Most notably, in the United States, the sequence type 18-IV (ST8-IV) clone known as USA300 has become highly prevalent, outcompeting methicillin-susceptible S. aureus (MSSA) and other MRSA strains in both community and hospital settings. CA-MRSA bacteria are much less prevalent in Europe, where the European ST80-IV European CA-MRSA clone, USA300 CA-MRSA strains, and other lineages, such as ST22-IV, coexist. The question that arises is whether the USA300 CA-MRSA present in Europe (i) was imported once or on very few occasions, followed by a broad geographic spread, anticipating an increased prevalence in the future, or (ii) derived from multiple importations with limited spreading success. In the present study, we applied whole-genome sequencing to a collection of French USA300 CA-MRSA strains responsible for sporadic cases and micro outbreaks over the past decade and United States ST8 MSSA and MRSA isolates. Genome-wide phylogenetic analysis demonstrated that the population structure of the French isolates is the product of multiple introductions dating back to the onset of the USA300 CA-MRSA clone in North America. Coalescent-based demography of the USA300 lineage shows that a strong expansion occurred during the 1990s concomitant with the acquisition of the arginine catabolic mobile element and antibiotic resistance, followed by a sharp decline initiated around 2008, reminiscent of the rise-and-fall pattern previously observed in the ST80 lineage. A future expansion of the USA300 lineage in Europe is therefore very unlikely. IMPORTANCE: To trace the origin, evolution, and dissemination pattern of the USA300 CA-MRSA clone in France, we sequenced a collection of strains of this lineage from cases reported in France in the last decade and compared them with 431 ST8 strains from the United States. We determined that the French CA-MRSA USA300 sporadic and micro-outbreak isolates resulted from multiple independent introductions of the USA300 North American lineage. At a global level, in the transition from an MSSA lineage to a successful CA-MRSA clone, it first became resistant to multiple antibiotics and acquired the arginine catabolic mobile element and subsequently acquired resistance to fluoroquinolones, and these two steps were associated with a dramatic demographic expansion. This expansion was followed by the current stabilization and expected decline of this lineage. These findings highlight the significance of horizontal gene acquisitions and point mutations in the success of such disseminated clones and illustrate their cyclic and sporadic life cycle. PMID- 26884430 TI - Chromatin Modulation of Herpesvirus Lytic Gene Expression: Managing Nucleosome Density and Heterochromatic Histone Modifications. AB - Like their cellular hosts, herpesviruses are subject to the regulatory impacts of chromatin assembled on their genomes. Upon infection, these viruses are assembled into domains of chromatin with heterochromatic signatures that suppress viral gene expression or euchromatic characteristics that promote gene expression. The organization and modulation of these chromatin domains appear to be intimately linked to the coordinated expression of the different classes of viral genes and thus ultimately play an important role in the progression of productive infection or the establishment and maintenance of viral latency. A recent report from the Knipe laboratory (J. S. Lee, P. Raja, and D. M. Knipe, mBio 7:e02007-15, 2016) contributes to the understanding of the dynamic modulation of chromatin assembled on the herpes simplex virus genome by monitoring the levels of characteristic heterochromatic histone modifications (histone H3 lysine 9 and 27 methylation) associated with a model viral early gene during the progression of lytic infection. Additionally, this study builds upon previous observations that the viral immediate-early protein ICP0 plays a role in reducing the levels of heterochromatin associated with the early genes. PMID- 26884431 TI - Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children. AB - Most patients with cerebral malaria (CM) sustain cerebral microvascular sequestration of Plasmodium falciparum-infected red blood cells (iRBCs). Although many young children are infected with P. falciparum, CM remains a rare outcome; thus, we hypothesized that specific host conditions facilitate iRBC cerebral sequestration. To identify these host factors, we compared the peripheral whole blood transcriptomes of Malawian children with iRBC cerebral sequestration, identified as malarial-retinopathy-positive CM (Ret+CM), to the transcriptomes of children with CM and no cerebral iRBC sequestration, defined as malarial retinopathy-negative CM (Ret-CM). Ret+CM was associated with upregulation of 103 gene set pathways, including cytokine, blood coagulation, and extracellular matrix (ECM) pathways (P < 0.01; false-discovery rate [FDR] of <0.05). Neutrophil transcripts were the most highly upregulated individual transcripts in Ret+CM patients. Activated neutrophils can modulate diverse host processes, including the ECM, inflammation, and platelet biology to potentially facilitate parasite sequestration. Therefore, we compared plasma neutrophil proteins and neutrophil chemotaxis between Ret+CM and Ret-CM patients. Plasma levels of human neutrophil elastase, myeloperoxidase, and proteinase 3, but not lactoferrin or lipocalin, were elevated in Ret+CM patients, and neutrophil chemotaxis was impaired, possibly related to increased plasma heme. Neutrophils were rarely seen in CM brain microvasculature autopsy samples, and no neutrophil extracellular traps were found, suggesting that a putative neutrophil effect on endothelial cell biology results from neutrophil soluble factors rather than direct neutrophil cellular tissue effects. Meanwhile, children with Ret-CM had lower levels of inflammation, higher levels of alpha interferon, and upregulation of Toll-like receptor pathways and other host transcriptional pathways, which may represent responses that do not favor cerebral iRBC sequestration. IMPORTANCE: There were approximately 198 million cases of malaria worldwide in 2013, with an estimated 584,000 deaths occurring mostly in sub-Saharan African children. CM is a severe and rare form of Plasmodium falciparum infection and is associated with high rates of mortality and neurological morbidity, despite antimalarial treatment. A greater understanding of the pathophysiology of CM would allow the development of adjunctive therapies to improve clinical outcomes. A hallmark of CM is cerebral microvasculature sequestration of P. falciparum-infected red blood cells (iRBCs), which results in vasculopathy in some patients. Our data provide a global analysis of the host pathways associated with CM and newly identify an association of activated neutrophils with brain iRBC sequestration. Products of activated neutrophils could alter endothelial cell receptors and coagulation to facilitate iRBC adherence. Future studies can now examine the role of neutrophils in CM pathogenesis to improve health outcomes. PMID- 26884432 TI - Immune Homeostatic Macrophages Programmed by the Bacterial Surface Protein NhhA Potentiate Nasopharyngeal Carriage of Neisseria meningitidis. AB - Neisseria meningitidis colonizes the nasopharyngeal mucosa of healthy populations asymptomatically, although the bacterial surface is rich in motifs that activate the host innate immunity. What determines the tolerant host response to this bacterium in asymptomatic carriers is poorly understood. We demonstrated that the conserved meningococcal surface protein NhhA orchestrates monocyte (Mo) differentiation specifically into macrophage-like cells with a CD200R(hi) phenotype (NhhA-Mphi). In response to meningococcal stimulation, NhhA-Mphi failed to produce proinflammatory mediators. Instead, they upregulated interleukin-10 (IL-10) and Th2/regulatory T cell (Treg)-attracting chemokines, such as CCL17, CCL18, and CCL22. Moreover, NhhA-Mphi were highly efficient in eliminating bacteria. The in vivo validity of these findings was corroborated using a murine model challenged with N. meningitidis systematically or intranasally. The NhhA modulated immune response protected mice from septic shock; Mo/Mphi depletion abolished this protective effect. Intranasal administration of NhhA induced an anti-inflammatory response, which was associated with N. meningitidis persistence at the nasopharynx. In vitro studies demonstrated that NhhA-triggered Mo differentiation occurred upon engaged Toll-like receptor 1 (TLR1)/TLR2 signaling and extracellular signal-regulated kinase (ERK) and Jun N-terminal protein kinase (JNK) activation and required endogenously produced IL-10 and tumor necrosis factor alpha (TNF-alpha). Our findings reveal a strategy that might be adopted by N. meningitidis to maintain asymptomatic nasopharyngeal colonization. IMPORTANCE: Neisseria meningitidis is an opportunistic human-specific pathogen that colonizes the nasopharyngeal mucosa asymptomatically in approximately 10% of individuals. Very little is known about how this bacterium evades immune activation during the carriage stage. Here, we observed that N. meningitidis, via the conserved surface protein NhhA, skewed monocyte differentiation into macrophages with a CD200R(hi) phenotype. Both in vivo and in vitro data demonstrated that these macrophages, upon meningococcal infection, played an important role in forming a homeostatic immune microenvironment through their capacity to eliminate invading bacteria and to generate anti-inflammatory mediators. This work provides novel insight into the mechanisms underlying the commensal persistence of N. meningitidis. PMID- 26884433 TI - Dynamic Remodeling of the Magnetosome Membrane Is Triggered by the Initiation of Biomineralization. AB - Magnetotactic bacteria produce chains of membrane-bound organelles that direct the biomineralization of magnetic nanoparticles. These magnetosome compartments are a model for studying the biogenesis and subcellular organization of bacterial organelles. Previous studies have suggested that discrete gene products build and assemble magnetosomes in a stepwise fashion. Here, using an inducible system, we show that the stages of magnetosome formation are highly dynamic and interconnected. During de novo formation, magnetosomes first organize into discontinuous chain fragments that are subsequently connected by the bacterial actin-like protein MamK. We also find that magnetosome membranes are not uniform in size and can grow in a biomineralization-dependent manner. In the absence of biomineralization, magnetosome membranes stall at a diameter of ~50 nm. Those that have initiated biomineralization then expand to significantly larger sizes and accommodate mature magnetic particles. We speculate that such a biomineralization-dependent checkpoint for membrane growth establishes the appropriate conditions within the magnetosome to ensure successful nucleation and growth of magnetic particles. IMPORTANCE: Magnetotactic bacteria make magnetic nanoparticles inside membrane-bound organelles called magnetosomes; however, it is unclear how the magnetosome membrane controls the biomineralization that occurs within this bacterial organelle. We placed magnetosome formation under inducible control in Magnetospirillum magneticum AMB-1 and used electron cryo tomography to capture magnetosomes in their near-native state as they form de novo. An inducible system provided the key evidence that magnetosome membranes grow continuously unless they have not properly initiated biomineralization. Our finding that the size of a bacterial organelle impacts its biochemical function is a fundamental advance that impacts our perception of organelle formation and can inform future attempts aimed at creating designer magnetic particles. PMID- 26884436 TI - Author's reply to Dubicka and colleagues and Stone. PMID- 26884435 TI - Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays. AB - Immunoassays are currently needed to quantify Loa loa microfilariae (mf). To address this need, we have conducted proteomic and bioinformatic analyses of proteins present in the urine of a Loa mf-infected patient and used this information to identify putative biomarkers produced by L. loa mf. In total, 70 of the 15,444 described putative L. loa proteins were identified. Of these 70, 18 were L. loa mf specific, and 2 of these 18 (LOAG_16297 and LOAG_17808) were biologically immunogenic. We developed novel reverse luciferase immunoprecipitation system (LIPS) immunoassays to quantify these 2 proteins in individual plasma samples. Levels of these 2 proteins in microfilaremic L. loa infected patients were positively correlated to mf densities in the corresponding blood samples (r = 0.71 and P < 0.0001 for LOAG_16297 and r = 0.61 and P = 0.0002 for LOAG_17808). For LOAG_16297, the levels in plasma were significantly higher in Loa-infected (geometric mean [GM], 0.045 ug/ml) than in uninfected (P < 0.0001), Wuchereria bancrofti-infected (P = 0.0005), and Onchocerca volvulus infected (P < 0.0001) individuals, whereas for LOAG_17808 protein, they were not significantly different between Loa-infected (GM, 0.123 ug/ml) and uninfected (P = 0.06) and W. bancrofti-infected (P = 0.32) individuals. Moreover, only LOAG_16297 showed clear discriminative ability between L. loa and the other potentially coendemic filariae. Indeed, the specificity of the LOAG_16297 reverse LIPS assay was 96% (with a sensitivity of 77%). Thus, LOAG_16297 is a very promising biomarker that will be exploited in a quantitative point-of-care immunoassay for determination of L. loa mf densities. IMPORTANCE: Loa loa, the causative agent of loiasis, is a parasitic nematode transmitted to humans by the tabanid Chrysops fly. Some individuals infected with L. loa microfilariae (mf) in high densities are known to experience post-ivermectin severe adverse events (SAEs [encephalopathy, coma, or death]). Thus, ivermectin-based mass drug administration (MDA) programs for onchocerciasis and for lymphatic filariasis control have been interrupted in parts of Africa where these filarial infections coexist with L. loa. To allow for implementation of MDA for onchocerciasis and lymphatic filariasis, tools that can accurately identify people at risk of developing post-ivermectin SAEs are needed. Our study, using host-based proteomics in combination with novel immunoassays, identified a single Loa specific antigen (LOAG_16297) that can be used as a biomarker for the prediction of L. loa mf levels in the blood of infected patients. Therefore, the use of such biomarker could be important in the point-of-care assessment of L. loa mf densities. PMID- 26884434 TI - Salmonella Suppresses the TRIF-Dependent Type I Interferon Response in Macrophages. AB - Salmonella enterica is an intracellular pathogen that causes diseases ranging from gastroenteritis to typhoid fever. Salmonella bacteria trigger an autophagic response in host cells upon infection but have evolved mechanisms for suppressing this response, thereby enhancing intracellular survival. We recently reported that S. enterica serovar Typhimurium actively recruits the host tyrosine kinase focal adhesion kinase (FAK) to the surface of the Salmonella-containing vacuole (SCV) (K. A. Owen et al., PLoS Pathog 10:e1004159, 2014). FAK then suppresses autophagy through activation of the Akt/mTORC1 signaling pathway. In FAK(-/-) macrophages, bacteria are captured in autophagosomes and intracellular survival is attenuated. Here we show that the cell-autonomous bacterial suppression of autophagy also suppresses the broader innate immune response by inhibiting production of beta interferon (IFN-beta). Induction of bacterial autophagy (xenophagy), but not autophagy alone, triggers IFN-beta production through a pathway involving the adapter TRIF and endosomal Toll-like receptor 3 (TLR3) and TLR4. Selective FAK knockout in macrophages resulted in rapid bacterial clearance from mucosal tissues after oral infection. Clearance correlated with increased IFN-beta production by intestinal macrophages and with IFN-beta-dependent induction of IFN-gamma by intestinal NK cells. Blockade of either IFN-beta or IFN gamma increased host susceptibility to infection, whereas experimental induction of IFN-beta was protective. Thus, bacterial suppression of autophagy not only enhances cell-autonomous survival but also suppresses more-systemic innate immune responses by limiting type I and type II interferons. IMPORTANCE: Salmonella enterica serovar Typhimurium represents one of the most commonly identified bacterial causes of foodborne illness worldwide. S. Typhimurium has developed numerous strategies to evade detection by the host immune system. Autophagy is a cellular process that involves the recognition and degradation of defective proteins and organelles. More recently, autophagy has been described as an important means by which host cells recognize and eliminate invading intracellular pathogens and plays a key role in the production of cytokines. Previously, we determined that Salmonella bacteria are able to suppress their own autophagic capture and elimination by macrophages. Building on that study, we show here that the inhibition of autophagy by Salmonella also prevents the induction of a protective cytokine response mediated by beta interferon (IFN beta) and IFN-gamma. Together, these findings identify a novel virulence strategy whereby Salmonella bacteria prevent cell autonomous elimination via autophagy and suppress the activation of innate immune responses. PMID- 26884437 TI - Speech Auditory Alerts Promote Memory for Alerted Events in a Video-Simulated Self-Driving Car Ride. AB - OBJECTIVE: Auditory displays could be essential to helping drivers maintain situation awareness in autonomous vehicles, but to date, few or no studies have examined the effectiveness of different types of auditory displays for this application scenario. BACKGROUND: Recent advances in the development of autonomous vehicles (i.e., self-driving cars) have suggested that widespread automation of driving may be tenable in the near future. Drivers may be required to monitor the status of automation programs and vehicle conditions as they engage in secondary leisure or work tasks (entertainment, communication, etc.) in autonomous vehicles. METHOD: An experiment compared memory for alerted events-a component of Level 1 situation awareness-using speech alerts, auditory icons, and a visual control condition during a video-simulated self-driving car ride with a visual secondary task. The alerts gave information about the vehicle's operating status and the driving scenario. RESULTS: Speech alerts resulted in better memory for alerted events. Both auditory display types resulted in less perceived effort devoted toward the study tasks but also greater perceived annoyance with the alerts. CONCLUSION: Speech auditory displays promoted Level 1 situation awareness during a simulation of a ride in a self-driving vehicle under routine conditions, but annoyance remains a concern with auditory displays. APPLICATION: Speech auditory displays showed promise as a means of increasing Level 1 situation awareness of routine scenarios during an autonomous vehicle ride with an unrelated secondary task. PMID- 26884438 TI - Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans. AB - Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 +/- 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. PMID- 26884439 TI - Combined Insulin Deficiency and Endotoxin Exposure Stimulate Lipid Mobilization and Alter Adipose Tissue Signaling in an Experimental Model of Ketoacidosis in Subjects With Type 1 Diabetes: A Randomized Controlled Crossover Trial. AB - Most often, diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. DKA is assumed to release proinflammatory cytokines and stress hormones that stimulate lipolysis and ketogenesis. We tested whether this perception of DKA can be reproduced in an experimental human model by using combined insulin deficiency and acute inflammation and tested which intracellular mediators of lipolysis are affected in adipose tissue. Nine subjects with type 1 diabetes were studied twice: 1) insulin-controlled euglycemia and 2) insulin deprivation and endotoxin administration (KET). During KET, serum tumor necrosis factor-alpha, cortisol, glucagon, and growth hormone levels increased, and free fatty acids and 3 hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone-sensitive lipase were altered. The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin-induced acute inflammation. The precipitating steps involve the release of proinflammatory cytokines and stress hormones, increased lipolysis, and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation. PMID- 26884440 TI - Epidemiological and Clinical Characteristics of Kawasaki Disease and Factors Associated with Coronary Artery Abnormalities in East China: Nine Years Experience. AB - BACKGROUND: Because of the different genetic backgrounds, living environments and economic conditions, the epidemiologic, clinical characteristics and risk factors for coronary artery abnormalities (CAAs) in the Chinese population may differ among different parts of China. METHODS: We did a retrospective study to explore the clinical characteristics and risk factors for CAAs in east China between 2006 and 2014. RESULTS: There were 1016 patients during the study period. Of the 1004 patients who completed echocardiographic studies, 23.9% had CAAs. Sex, serum albumin, erythrocyte sedimentation rate (ESR),Mycoplasma pneumoniae(MP) infection, intravenous immunoglobulin (IVIG) started after the 10th day of illness and IVIG non-responders were independent risk factors associated with CAA. CONCLUSIONS: East China has a lower incidence of CAAs compared with southwest and northeast China, while similar to north China. Male gender, serum albumin, ESR, MP infection, IVIG started after the 10th day of illness and IVIG non-responders were predictive of CAA. PMID- 26884441 TI - The Burden of Child Maltreatment Leading to Hospitalization in a Provincial Setting in Papua New Guinea. AB - INTRODUCTION: Child maltreatment is prevalent globally. In Papua New Guinea (PNG), child maltreatment remains an under-reported problem. METHODS: As part of a 10 month prospective observational study conducted at Modilon Hospital in PNG, we investigated the burden of child maltreatment in the form of sexual abuse, physical abuse and neglect, leading to hospitalization in children <=14 years. RESULTS: Of 1061 screened admissions, 107 (10%) fulfilled the definition of child maltreatment. The in-hospital admission prevalence of sexual abuse was 5.7% [60 of 1061; 95% confidence interval (CI): 4.4-7.3]. Neglect accounted for 3.4% (36 of 1061; 95% CI: 2.4-4.7) of admissions, while physical abuse accounted for 1.0% (11 of 1061; 95% CI: 0.6-1.9). Mortality was highest in the neglected group, with severe acute malnutrition accounting for 89% of deaths. CONCLUSION: Improved awareness, establishment of appropriate channels for addressing child maltreatment and enforcement of child protection laws in PNG and other epidemiologically similar settings are urgently needed. PMID- 26884442 TI - Clinical Severity and Rotavirus Vaccination among Children Hospitalized for Acute Gastroenteritis in Belem, Northern Brazil. AB - In March 2006, Brazil introduced the monovalent rotavirus (RV) vaccine (RotarixTM) into the public sector. This study assessed the severity of rotavirus gastroenteritis (RVGE) according to the vaccination status among hospitalized children. We identified 1023 RVGE episodes among not vaccinated (n = 252), partially vaccinated (n = 156) and fully vaccinated (n = 615) children. Very severe gastroenteritis (scored >= 15) was reported in 16.7, 17.9 and 13.5% of not vaccinated, partially vaccinated and fully vaccinated children, respectively. There was a trend for a shorter duration of RV diarrhoea among vaccinated children than in not vaccinated children (p = 0.07). A protective effect of vaccination was noted when mean duration of symptoms and hospital stay are analysed, comparing unvaccinated, partially vaccinated and fully vaccinated children (p < 0.05). We showed a vaccination dose effect trend, with fully vaccinated children having less-severe RVGE than not vaccinated and partially vaccinated children. PMID- 26884443 TI - Seroprevalence of CMV, HSV-2 and HBV among HIV-Infected Malawian Children: A Cross-sectional Survey. AB - BACKGROUND: Little is known about viral co-infections in African human immunodeficiency virus (HIV)-infected children. We examined the prevalence of seromarkers for cytomegalovirus (CMV), herpes simplex virus type 2 (HSV-2) and hepatitis B virus (HBV) infections among HIV-infected, antiretroviral treatment (ART)-naive children in Lilongwe, Malawi. METHODS: Ninety-one serum samples were tested for IgG and IgM antibodies to CMV, and IgG antibodies to HSV-2 and hepatitis B surface antigen (HBsAg). Baseline demographic, clinical and laboratory data were abstracted from electronic records. RESULTS: CMV IgG was the most common positive result in all age groups (in 73% of children <1 year, and 100% in all other groups). Three patients were CMV IgM positive (3.3%), suggesting acute infection. HSV-2 IgG was positive in four patients (4.4%), and HBsAg in two (2.2%). CONCLUSIONS: CMV infection occurred early in life, and few children had specific signs of CMV infection at the time of ART initiation. Unrecognized HBV infection represents opportunities for testing and treatment of HIV/HBV co-infected children. PMID- 26884444 TI - Risk factors for respiratory infections among children attending day care centres. AB - BACKGROUND: Upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI) and acute otitis media (AOM) are common in children attending day care centres. OBJECTIVES: This study aimed to characterize the risk factors of URTI, LRTI and AOM in children attending day care. METHODS: A cross-sectional study was conducted in children aged up to 3 years (n = 152) of six day care centres in Porto. Logistic regression was used on independent variables: mother related, household-related, child-related and day care-related risk factors as predictors of the dependent variables: URTI, LRTI and AOM. RESULTS: The risk of URTI increased as the number of children decreased [odds ratio (OR) = 0.620, 95% CI = 0.411-0.935], as the area per child decreased (OR = 0.434, 95% CI = 0.206 0.914) and as the disinfection of WC/diapers-change increased (OR = 2.56, 95% CI = 1.089-6.017). There was a higher risk of URTI if nasal aspirators (OR = 6.763, 95% CI = 1.022-44.753), rather than physiologic serum (OR = 5.296, 95% CI = 1.097 25.559), were used at day care centres. The risk of LRTI increased as the household size decreased (OR = 0.213, 95% CI = 0.048-0.937) and it was higher if the child had no siblings (OR = 7.831, 95% CI = 1.065-57.578). The risk of LRTI was higher if the child was not exclusively breastfed (OR = 24.612, 95% CI = 1.108-546.530) and the risk increased as the duration of exclusive breastfeeding decreased (OR = 0.396, 95% CI = 0.170-0.920). The risk of AOM increased as the birth body mass index (OR = 2.247, 95% CI = 1.011-4.992) and weight (OR = 1.607, 95% CI = 1.014-2.545) increased and if nasal aspirators were used (OR = 6.763, 95% CI = 1.022-44.753). CONCLUSION: URTI were related with day care centres' risk factors, LRTI were associated with mother-related and household-related risk factors and AOM was connected with child-related risk factors. PMID- 26884445 TI - Relationship between depressive symptoms, alcohol use, and antiretroviral therapy adherence among HIV-infected, clinic-attending patients in South Africa. AB - Despite the prevalence of depression and alcohol use among HIV-infected individuals, few studies have examined their association together in relation to nonadherence to antiretroviral therapy in sub-Saharan Africa. This study examined depressive symptoms, alcohol use, and other psychosocial factors (stigma, demographic characteristics) in relation to nonadherence to antiretroviral therapy among clinic-attending, HIV-infected individuals in South Africa ( n = 101). Nonadherence was assessed using event-level measurement (missed doses over the past weekend). Multivariable logistic regression analyses revealed that only alcohol use, over and above depressive symptoms and education level, was associated with antiretroviral therapy nonadherence(AOR = 1.15; 95%CI = 1.02 1.29; p < .05). Findings point to the independent association of alcohol use and nonadherence to antiretroviral therapy above and beyond depressive symptoms. PMID- 26884446 TI - The Ratio of Inspiratory Pressure Over Electrical Activity of the Diaphragm Remains Stable During ICU Stay and is not Related to Clinical Outcome. AB - BACKGROUND: We previously described an index, defined as the ratio between the inspiratory muscle pressure (Pmus) and the electrical activity of the diaphragm (EA(di)) (Pmus/EA(di) index). In the present work, we describe the trend of Pmus/EA(di) index over time, investigating whether it could be an indicator of muscular efficiency associated with risk factors for diaphragmatic injury and/or clinical outcomes. METHODS: This work is a retrospective analysis of subjects with measurements of Pmus/EA(di) index obtained, on different days, during assisted ventilation. Effects of Pmus/EA(di) index absolute value on clinical outcomes were investigated dividing subjects into those with Pmus/EA(di) index higher or lower than the median. Effects of Pmus/EA(di) index trend over time were analyzed, distinguishing between subjects with Pmus/EA(di) index increasing or decreasing. RESULTS: Mean Pmus/EA(di) index was 1.04 +/- 0.67, and the median (interquartile range) was 1.00 (0.59-1.34), without a systematic trend over the days. Demographic, ventilator, or outcome data did not significantly differ between subjects with Pmus/EA(di) index higher or lower than the median. Similarly, we did not find relevant differences in subjects with Pmus/EA(di) index increasing or decreasing over time. CONCLUSIONS: The Pmus/EA(di) index value remained constant in each subject over time, although the inter-individual variability was high. Neither the Pmus/EA(di) index nor its trends appeared to be associated with ventilatory variables or clinical outcome. PMID- 26884447 TI - Clinical Utility of Additional Measurement of Total Lung Capacity in Diagnosing Obstructive Lung Disease in Subjects With Restrictive Pattern of Spirometry. AB - BACKGROUND: Total lung capacity (TLC), forced expiratory flow between 25 and 75% (FEF25-75%), peak expiratory flow (PEF), or post-bronchodilator volume response is recommended to detect obstructive abnormalities in the lung. The present study was performed to evaluate the usefulness of these pulmonary function test (PFT) parameters to diagnose obstructive lung disease in subjects with a restrictive pattern of spirometry. METHODS: A retrospective study was conducted in 64 subjects with a restrictive pattern of spirometry (normal FEV1/FVC and low FVC) out of 3,030 patients who underwent all pre- and post-bronchodilator spirometry and lung volume measurement between April 2008 and December 2010. After subjects were clinically classified into those with obstructive lung disease, restrictive lung disease, and mixed lung disease, the agreements between the clinical diagnosis and PFT classification according to TLC, FEF(25-75%), PEF, and post bronchodilator response criteria were compared. RESULTS: Of 64 subjects, 18 (28.1%) were classified with obstructive lung disease, 39 (60.9%) had restrictive lung disease, 1 (1.6%) had mixed lung disease, and 6 (9.4%) had no clinical lung disease. Among the 58 subjects with clinical lung disease, 22 (37.9%), 37 (63.8%), 33 (56.9%), and 3 (5.2%) were classified as having obstructive pattern based on TLC, FEF25-75%, PEF, and post-bronchodilator response criteria, respectively. The kappa coefficients for the agreement between the clinical classification and PFT classification using TLC, FEF25-75%, PEF, and post bronchodilator response criteria in 58 subjects were 0.59, 0.18, 0.17, and < 0.01, respectively. CONCLUSIONS: The additional measurement of TLC is more useful than FEF25-75%, PEF, and post-bronchodilator response for diagnosis of obstructive lung disease in subjects with a restrictive pattern of spirometry, when obstructive lung disease is clinically suspected. PMID- 26884448 TI - Migration of a Needle From the Chest Wall Into the Right Ventricle in a 10-Year Old Child. AB - Cardiac foreign bodies are rare in children and the nature or timing of the injury may be hard to ascertain. We report a case of a 10-year-old boy who presented with a 28-mm solid core needle in the left chest wall that advanced into his right ventricle, possibly from soft tissue manipulation. Computed tomography, intraoperative fluoroscopy, and echocardiography were necessary to locate the needle and successfully remove it surgically. PMID- 26884449 TI - Isolated Left Subclavian Artery From the Pulmonary Artery Masked by Pulmonary Hypertension. AB - Isolated subclavian artery arising from the pulmonary artery is exceedingly rare. Most cases are associated with other forms of congenital heart disease and typically present with subclavian or pulmonary steal syndromes. We report the case of a patient with pulmonary hypertension which masked the isolated subclavian artery, allowing it to masquerade as another common congenital heart lesion. PMID- 26884450 TI - A Case of Giant Right Atrial Aneurysm in a Child. AB - Giant right atrial aneurysm is a rare entity in infants and children. It needs to be distinguished from an atrial diverticulum, which can have similar presentation. Generally, an incidental finding in children, it can present with varied symptoms. We report a case of a giant right atrial aneurysm in an asymptomatic child with a large clot in the dilated right atrium, who underwent successful resection of the atrial aneurysm. PMID- 26884451 TI - Desmoid Tumor After a Minimally Invasive Atrial Septal Defect Closure in an Adolescent. AB - The surgical closure of secundum atrial septal defect (ASD) is frequently performed. The minimally invasive approach, currently adopted by many centers as a way to preserve aesthetic appearance, particularly in female patients, seems to be safe. We describe the case of an adolescent who developed a desmoid tumor soon after a minimally invasive operation for surgical closure of a secundum ASD. PMID- 26884452 TI - Large Right Ventricular Clot in Pulmonary Atresia With Intact Ventricular Septum: In Defense of Biventricular Approach. AB - Thrombus formation within the right ventricle (RV) in the setting of pulmonary atresia with intact ventricular septum (PAIVS) is not a very common occurrence and can be catastrophic. We present the case of a seven-month-old child with PAIVS and RV clot who successfully underwent biventricular repair. We discuss the interesting case and the rationale for management by means of biventricular repair over single ventricle repair when feasible in such a setting. PMID- 26884453 TI - Left Isomerism of the Atrial Appendages With Sinus Venosus Defect and Anomalous Systemic Venous Drainage. AB - We present a case with left isomerism, interruption of the inferior caval vein, anomalous systemic venous drainage with partially anomalous pulmonary venous drainage, and a sinus venosus type of atrial septal defect in the absence of a right superior caval vein. This report is of interest because of a rare combination of these anomalies, which was accurately diagnosed and successfully repaired. PMID- 26884455 TI - Zika Virus Infection Presenting with Postauricular Lymphadenopathy. PMID- 26884454 TI - The matricellular protein CCN1 enhances TGF-beta1/SMAD3-dependent profibrotic signaling in fibroblasts and contributes to fibrogenic responses to lung injury. AB - Matricellular proteins mediate pleiotropic effects during tissue injury and repair. CCN1 is a matricellular protein that has been implicated in angiogenesis, inflammation, and wound repair. In this study, we identified CCN1 as a gene that is differentially up-regulated in alveolar mesenchymal cells of human subjects with rapidly progressive idiopathic pulmonary fibrosis (IPF). Elevated levels of CCN1 mRNA were confirmed in lung tissues of IPF subjects undergoing lung transplantation, and CCN1 protein was predominantly localized to fibroblastic foci. CCN1 expression in ex vivo IPF lung fibroblasts correlated with gene expression of the extracellular matrix proteins, collagen (Col)1a1, Col1a2, and fibronectin as well as the myofibroblast marker, alpha-smooth muscle actin. RNA interference (RNAi)-mediated knockdown of CCN1 down-regulated the constitutive expression of these profibrotic genes in IPF fibroblasts. TGF-beta1, a known mediator of tissue fibrogenesis, induces gene and protein expression of CCN1 via a mothers against decapentaplegic homolog 3 (SMAD3)-dependent mechanism. Importantly, endogenous CCN1 potentiates TGF-beta1-induced SMAD3 activation and induction of profibrotic genes, supporting a positive feedback loop leading to myofibroblast activation. In vivo RNAi-mediated silencing of CCN1 attenuates fibrogenic responses to bleomycin-induced lung injury. These studies support previously unrecognized, cooperative interaction between the CCN1 matricellular protein and canonical TGF-beta1/SMAD3 signaling that promotes lung fibrosis. Kurundkar, A. R., Kurundkar, D., Rangarajan, S., Locy, M. L., Zhou, Y., Liu, R. M., Zmijewski, J., Thannickal, V. J. The matricellular protein CCN1 enhances TGF beta1/SMAD3-dependent profibrotic signaling in fibroblasts and contributes to fibrogenic responses to lung injury. PMID- 26884456 TI - Ex vivo effects of naphthoquinones on allergen-sensitized mononuclear cells in mice. AB - Naphthoquinone (NQ), one of the extractable chemical compounds of diesel exhaust particles, enhances allergic asthma traits in mice. However, it remains unknown whether: (1) several types of NQs have the same potential to facilitate allergies; and (2) NQs synergistically disrupt the functional phenotypes of immune cells. The aim of the present study was to investigate the effects of two types (1,2- and 1,4-) of NQs on sensitized mononuclear cells using an ex vivo assay. Male BALB/c mice were repeatedly and intraperitoneally administered ovalbumin (OVA: 20 ug) plus alum with or without two different doses of each NQ. After the final administration, splenocytes (mononuclear cells) were isolated from these mice and cultured in the presence of OVA. Helper T-related cytokines in the culture supernatants and downstream molecules were then evaluated. Protein levels of interferon-gamma were higher in the supernatants from 1,2-NQ and 1,4-NQ at low dose + OVA-exposed mononuclear cells following the OVA stimulation than in those from OVA-exposed mononuclear cells. Interleukin (IL)-13 levels were higher in the supernatants from low dose NQs + OVA-exposed mononuclear cells. IL-17 levels were significantly higher in the supernatants from low dose 1,2-NQ + OVA exposed mononuclear cells. The quantity of phosphorylated STAT6 in the nuclei of these cells was significantly greater in the low dose NQ + OVA groups than in the OVA group. These findings suggest NQs differently enhance allergen sensitization in the context of the Th response against mononuclear cells such as lymphocytes. PMID- 26884458 TI - Challenges and management issues in adults with cyanotic congenital heart disease. PMID- 26884457 TI - Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma. AB - BACKGROUND: Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. STUDY DESIGN: An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. MATERIALS AND METHODS: Female nude mice were implanted with rat leiomyoma cells subcutaneously. Then mice were randomized into three groups. Group 1 received Ad-LacZ (marker gene), Group 2 received untargeted Ad TK, and Group 3 received the targeted Ad-SSTR-RGD-TK. Tumors were measured weekly for 4 weeks. Then mice were sacrificed and tissue samples were collected. Evaluation of markers of apoptosis, proliferation, extracellular matrix, and angiogenesis was performed using Western Blot & Immunohistochemistry. Statistical analysis was done using ANOVA. Dissemination of adenovirus was assessed by PCR. RESULTS: In comparison with the untargeted vector, the targeted adenoviral vector significantly shrank leiomyoma size (P < 0.05), reduced expression of proliferation marker (PCNA) (P < 0.05), induced expression of apoptotic protein, c-PARP-1, (P < 0.05) and inhibited expression of extracellular matrix-related genes (TGF beta 3) and angiogenesis-related genes (VEGF & IGF-1) (P < 0.01). There were no detectable adenovirus in tested tissues other than leiomyoma lesions with both targeted and untargeted adenovirus. CONCLUSION: Targeted adenovirus, effectively reduces tumor size in leiomyoma without dissemination to other organs. Further evaluation of this localized targeted strategy for gene therapy is needed in appropriate preclinical humanoid animal models in preparation for a future pilot human trial. PMID- 26884459 TI - Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes. AB - The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1beta, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells. PMID- 26884460 TI - Dynamic macrophage polarization-specific miRNA patterns reveal increased soluble VEGF receptor 1 by miR-125a-5p inhibition. AB - Dynamic, epigenetic mechanisms can regulate macrophage phenotypes following exposure to different stimulating conditions and environments. However, temporal patterns of microRNAs (miRNAs or miRs) across multiple macrophage polarization phenotypes have not been defined. We determined miRNA expression in bone marrow derived murine macrophages over multiple time points (0.5, 1, 3, 24 h) following exposure to cytokines and/or LPS. We hypothesized that dynamic changes in miRNAs regulate macrophage phenotypes. Changes in macrophage polarization markers were detected as early as 0.5 and as late as 24 h; however, robust responses for most markers occurred within 3 h. In parallel, many polarization-specific miRNAs were also changed by 3 h and expressed divergent patterns between M1 and M2a conditions, with increased expression in M1 (miR-155, 199a-3p, 214-3p, 455-3p, and 125a) or M2a (miR-511 and 449a). Specifically, miR-125a-5p exhibited divergent patterns: increased at 12-24 h in M1 macrophages and decreasing trend in M2a. VEGF in the culture media of macrophages was dependent upon the polarization state, with greatly diminished VEGF in M2a compared with M1 macrophage culture media despite similar VEGF in cell lysates. Inhibition of miR 125a-5p in media-only controls (MO) and M1 macrophages greatly increased expression and secretion of soluble VEGF receptor-1 (sVEGFR1) leading to diminished VEGF in the culture media, partially converting MO and M1 into an M2a phenotype. Thus, the divergent expression patterns of polarization-specific miRNAs led to the identification and demonstrated the regulation of a specific macrophage polarization phenotype, sVEGFR1 by inhibition of miR-125a-5p. PMID- 26884461 TI - Age-dependent differences in microglial responses to systemic inflammation are evident as early as middle age. AB - Whereas age increases microglial inflammatory activities and impairs their ability to effectively regulate their immune response, it is unclear at what age these exaggerated responses begin. We tested the hypotheses that augmented microglial responses to inflammatory challenge are present as early as middle age and that repeated stimulation of primed microglia in vivo would reveal microglial senescence. Microglial gene expression was investigated in a mouse model of repeated systemic inflammation induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). Following LPS, microglia from middle-aged mice (9-10 mo) displayed larger increases in Tnfalpha, Il-6, and Il-1beta gene expression compared with young adults (2 mo). Similar results were observed in the spleens of middle-aged mice, indicating that exaggeration of both central and peripheral immune responses are already evident at early middle age. Interestingly, despite greater proinflammatory responses to the first LPS challenge in the aged mice, there were no age-dependent differences in either microglia or spleen following a subsequent LPS dose, suggesting that animals at this age retain the ability to effectively control their immune response following repeated challenge. The exacerbated microglial immune response to systemic inflammation at early middle age suggests that the CNS may be vulnerable to age-dependent alterations earlier than previously appreciated. PMID- 26884463 TI - A Remodeled Hsp90 Molecular Chaperone Ensemble with the Novel Cochaperone Aarsd1 Is Required for Muscle Differentiation. AB - Hsp90 is the ATP-consuming core component of a very abundant molecular chaperone machine that handles a substantial portion of the cytosolic proteome. Rather than one machine, it is in fact an ensemble of molecular machines, since most mammalian cells express two cytosolic isoforms of Hsp90 and a subset of up to 40 to 50 cochaperones and regulate their interactions and functions by a variety of posttranslational modifications. We demonstrate that the Hsp90 ensemble is fundamentally remodeled during muscle differentiation and that this remodeling is not just a consequence of muscle differentiation but possibly one of the drivers to accompany and to match the vast proteomic changes associated with this process. As myoblasts differentiate into myotubes, Hsp90alpha disappears and only Hsp90beta remains, which is the only isoform capable of interacting with the novel muscle-specific Hsp90 cochaperone Aarsd1L. Artificially maintaining Hsp90alpha or knocking down Aarsd1L expression interferes with the differentiation of C2C12 myotubes. During muscle differentiation, Aarsd1L replaces the more ubiquitous cochaperone p23 and in doing so dampens the activity of the glucocorticoid receptor, one of the Hsp90 clients relevant to muscle functions. This cochaperone switch protects muscle cells against the inhibitory effects of glucocorticoids and may contribute to preventing muscle wasting induced by excess glucocorticoids. PMID- 26884462 TI - Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus. AB - Histone chaperones, like nucleosome assembly protein 1 (Nap1), play a critical role in the maintenance of chromatin architecture. Here, we use the GAL locus in Saccharomyces cerevisiae to investigate the influence of Nap1 on chromatin structure and histone dynamics during distinct transcriptional states. When the GAL locus is not expressed, cells lacking Nap1 show an accumulation of histone H2A-H2B but not histone H3-H4 at this locus. Excess H2A-H2B interacts with the linker DNA between nucleosomes, and the interaction is independent of the inherent DNA-binding affinity of H2A-H2B for these particular sequences as measured in vitro When the GAL locus is transcribed, excess H2A-H2B is reversed, and levels of all chromatin-bound histones are depleted in cells lacking Nap1. We developed an in vivo system to measure histone exchange at the GAL locus and observed considerable variability in the rate of exchange across the locus in wild-type cells. We recapitulate this variability with in vitro nucleosome reconstitutions, which suggests a contribution of DNA sequence to histone dynamics. We also find that Nap1 is required for transcription-dependent H2A-H2B exchange. Altogether, these results indicate that Nap1 is essential for maintaining proper chromatin composition and modulating the exchange of H2A-H2B in vivo. PMID- 26884464 TI - Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon. AB - Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx(-/-) mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration. PMID- 26884466 TI - The genome of the Antarctic polyextremophile Nesterenkonia sp. AN1 reveals adaptive strategies for survival under multiple stress conditions. AB - Nesterenkonia sp. AN1 is a polyextremophile isolated from Antarctic desert soil. Genomic analyses and genome comparisons with three mesophilic Nesterenkonia strains indicated that the unique genome fraction of Nesterenkonia sp. AN1 contains adaptive features implicated in the response to cold stress including modulation of membrane fluidity as well as response to cold-associated osmotic and oxidative stress. The core genome also encodes a number of putative cold stress response proteins. RNA-Seq-based transcriptome analyses of Nesterenkonia sp. AN1 grown at 5oC and 21 degrees C showed that there was significant induction of transcripts that code for antioxidants at 5oC, demonstrated by the upregulation of sodA, bcp and bpoA2. There was also overexpression of universal stress protein genes related to uspA, along with genes encoding other characterized cold stress features. Genes encoding the two key enzymes of the glyoxylate cycle, isocitrate lyase (ICL) and malate synthase (AceB) were induced at 5oC, suggesting possible adaptation strategies for energy metabolism in cold habitats. These genomic features may contribute to the survival of Nesterenkonia sp. AN1 in arid Antarctic soils. PMID- 26884465 TI - H19 Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR. AB - The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. The H19 long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report that H19 plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675). H19 overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressing H19 prevented the stimulation of miR-675 processing from H19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate that H19 interacts with HuR and regulates the intestinal epithelial barrier function via the H19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally. PMID- 26884468 TI - The Use of Crime Scene and Demographic Information in the Identification of Non Serial Sexual Homicide. AB - As with other sexual offenders, sexual homicide perpetrators can be reluctant to talk about their criminal behavior. Therefore, in homicide cases, forensic practitioners frequently rely on crime scene information to identify any sexual behavior associated with the offense. This study aims to identify objective and readily available crime scene information, alongside information about victims and perpetrators, based on 65 cases from England and Wales in the United Kingdom of men convicted of homicide who had committed a non-serial sexual homicide and 64 cases of men convicted of homicide where the available evidence indicated that it was a non-serial non-sexual homicide. Chi-square tests and logistic regression were used to analyze the data. There were few differences in terms of demographic information and criminal histories between the two perpetrator groups. There were crime scene indicators supporting the use of Ressler et al.'s definition of sexual homicide. The victims of sexual homicide were generally found in their home with the lower half of the body exposed and with evidence of vaginal sex. Furthermore, extreme injuries and strangulation were more frequent in sexual homicides. Use of weapon was associated with a non-sexual homicide. Victims of sexual homicide were as likely to know the perpetrator as not. Potential benefits of the characteristics reported to investigators and forensic practitioners tasked with identifying sexual homicides are discussed and areas for further research suggested. PMID- 26884467 TI - Ecophysiology, secondary pigments and ultrastructure of Chlainomonas sp. (Chlorophyta) from the European Alps compared with Chlamydomonas nivalis forming red snow. AB - Red snow is a well-known phenomenon caused by microalgae thriving in alpine and polar regions during the melting season. The ecology and biodiversity of these organisms, which are adapted to low temperatures, high irradiance and freeze-thaw events, are still poorly understood. We compared two different snow habitats containing two different green algal genera in the European Alps, namely algae blooming in seasonal rock-based snowfields (Chlamydomonas nivalis) and algae dominating waterlogged snow bedded over ice (Chlainomonassp.). Despite the morphological similarity of the red spores found at the snow surface, we found differences in intracellular organization investigated by light and transmission electron microscopy and in secondary pigments investigated by chromatographic analysis in combination with mass spectrometry. Spores ofChlainomonassp. show clear differences fromChlamydomonas nivalisin cell wall arrangement and plastid organization. Active photosynthesis at ambient temperatures indicates a high physiological activity, despite no cell division being present. Lipid bodies containing the carotenoid astaxanthin, which produces the red color, dominate cells of both species, but are modified differently. While inChlainomonassp. astaxanthin is mainly esterified with two fatty acids and is more apolar, inChamydomonas nivalis, in contrast, less apolar monoesters prevail. PMID- 26884469 TI - Public views on the role of government in funding and delivering health services. AB - AIMS: Public surveys in socialized health systems indicate strong support for the role of government in health care, although different views can be detected. The study considers the public's views on public versus private funding and delivery of health services. METHODS: The study is based on a representative national sample of 1532 Icelandic adults, aged 18 and older, who participated in a national public issues survey. Respondents were asked about government spending on health care and whether the government or private parties should deliver health services. RESULTS: The great majority of respondents thought that the government should spend more on health care, and should be the primary provider of care. Lower age, female gender, countryside residence, and expected high use of health care were related to greater support for governmental funding. Furthermore, countryside residence, less education, lower income, not being a governmental health worker, expected high health care use, and left-wing political ideology were all related to greater support for governmental delivery of health care. CONCLUSIONS DESPITE SOCIODEMOGRAPHIC VARIATIONS, THE STUDY FINDS STRONG OVERALL SUPPORT FOR THE ROLE OF GOVERNMENT IN FUNDING AND DELIVERING HEALTH CARE PREVIOUS PERSPECTIVES AND HYPOTHESES OF WELFARE STATE ENDORSEMENT RECEIVED MIXED SUPPORT, SUGGESTING THAT FURTHER THEORETICAL AND EMPIRICAL WORK IS NEEDED TO BETTER ACCOUNT FOR PUBLIC VIEWS ON THE ROLE OF GOVERNMENT IN HEALTH CARE. PMID- 26884470 TI - Activins in reproductive biology and beyond. AB - BACKGROUND: Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-beta) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology. It also discusses interesting advances in the field of modulating the bioactivity of activins as a therapeutic target, which would undoubtedly be beneficial for patients with reproductive pathology. METHODS: A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies in the English language which have contributed to the advancement of the field of activin biology, since its initial isolation in 1987 until July 2015. 'Activin', 'testis', 'ovary', 'embryonic development' and 'therapeutic targets' were used as the keywords in combination with other search phrases relevant to the topic of activin biology. RESULTS: Activins, which are dimers of inhibin beta subunits, act via a classical TGF-beta signalling pathway. The bioactivity of activin is regulated by two endogenous inhibitors, inhibin and follistatin. Activin is a major regulator of testicular and ovarian development. In the ovary, activin A promotes oocyte maturation and regulates granulosa cell steroidogenesis. It is also essential in endometrial repair following menstruation, decidualization and maintaining pregnancy. Dysregulation of the activin-follistatin-inhibin system leads to disorders of female reproduction and pregnancy, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, fetal growth restriction, gestational diabetes, pre-eclampsia and pre-term birth. Moreover, a rise in serum activin A, accompanied by elevated FSH, is characteristic of female reproductive aging. In the male, activin A is an autocrine and paracrine modulator of germ cell development and Sertoli cell proliferation. Disruption of normal activin signalling is characteristic of many tumours affecting reproductive organs, including endometrial carcinoma, cervical cancer, testicular and ovarian cancer as well as prostate cancer. While activin A and B aid the progression of many tumours of the reproductive organs, activin C acts as a tumour suppressor. Activins are important in embryonic induction, morphogenesis of branched glandular organs, development of limbs and nervous system, craniofacial and dental development and morphogenesis of the Wolffian duct. CONCLUSIONS: The field of activin biology has advanced considerably since its initial discovery as an FSH stimulating agent. Now, activin is well known as a growth factor and cytokine that regulates many aspects of reproductive biology, developmental biology and also inflammation and immunological mechanisms. Current research provides evidence for novel roles of activins in maintaining the structure and function of reproductive and other organ systems. The fact that activin A is elevated both locally as well as systemically in major disorders of the reproductive system makes it an important biomarker. Given the established role of activin A as a pro inflammatory and pro-fibrotic agent, studies of its involvement in disorders of reproduction resulting from these processes should be examined. Follistatin, as a key regulator of the biological actions of activin, should be evaluated as a therapeutic agent in conditions where activin A overexpression is established as a contributing factor. PMID- 26884471 TI - Magnetic resonance imaging for assessment of cerebrovascular reactivity in cerebral small vessel disease: A systematic review. AB - Cerebral small vessel disease (SVD) pathophysiology is poorly understood. Cerebrovascular reactivity (CVR) impairment may play a role, but evidence to date is mainly indirect. Magnetic resonance imaging (MRI) allows investigation of CVR directly in the tissues affected by SVD. We systematically reviewed the use of MRI to measure CVR in subjects with SVD. Five studies (total n = 155 SVD subjects, 84 controls) provided relevant data. The studies included different types of patients. Each study used blood oxygen level dependent (BOLD) MRI to assess CVR but a different vasoactive stimulus and method of calculating CVR. CVR decreased with increasing white matter hyperintensities in two studies (n = 17, 11%) and in the presence of microbleeds in another. Three studies (n = 138, 89%) found no association of CVR with white matter hyperintensities. No studies provided tissue-specific CVR values. CVR decreased with age in three studies, and with female gender and increasing diastolic blood pressure in one study. Safety and tolerability data were limited. Larger studies using CVR appear to be feasible and are needed, preferably with more standardized methods, to determine if specific clinical or radiological features of SVD are more or less associated with impaired CVR. PMID- 26884473 TI - Long-Acting C-Peptide and Neuropathy in Type 1 Diabetes: A 12-Month Clinical Trial. AB - OBJECTIVE: Lack of C-peptide in type 1 diabetes may be an important contributing factor in the development of microvascular complications. Replacement of native C peptide has been shown to exert a beneficial influence on peripheral nerve function in type 1 diabetes. The aim of this study was to evaluate the efficacy and safety of a long-acting C-peptide in subjects with type 1 diabetes and mild to moderate peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 250 patients with type 1 diabetes and peripheral neuropathy received long-acting (pegylated) C-peptide in weekly dosages of 0.8 mg (n = 71) or 2.4 mg (n = 73) or placebo (n = 106) for 52 weeks. Bilateral sural nerve conduction velocity (SNCV) and vibration perception threshold (VPT) on the great toe were measured on two occasions at baseline, at 26 weeks, and at 52 weeks. The modified Toronto Clinical Neuropathy Score (mTCNS) was used to grade the peripheral neuropathy. RESULTS: Plasma C-peptide rose during the study to 1.8-2.2 nmol/L (low dose) and to 5.6-6.8 nmol/L (high dose). After 52 weeks, SNCV had increased by 1.0 +/- 0.24 m/s (P < 0.001 within group) in patients receiving C-peptide (combined groups), but the corresponding value for the placebo group was 1.2 +/- 0.29 m/s. Compared with basal, VPT had improved by 25% after 52 weeks of C-peptide therapy (Delta for combined C-peptide groups: -4.5 +/- 1.0 MUm, placebo group: -0.1 +/- 0.9 MUm; P < 0.001). mTCNS was unchanged during the study. CONCLUSIONS: Once-weekly subcutaneous administration of long-acting C-peptide for 52 weeks did not improve SNCV, other electrophysiological variables, or mTCNS but resulted in marked improvement of VPT compared with placebo. PMID- 26884472 TI - Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes. AB - OBJECTIVE: Treatment of severe hypoglycemia outside of the hospital setting is limited to intramuscular glucagon requiring reconstitution prior to injection. The current study examined the safety and dose-response relationships of a needle free intranasal glucagon preparation in youth aged 4 to <17 years. RESEARCH DESIGN AND METHODS: A total of 48 youth with type 1 diabetes completed the study at seven clinical centers. Participants in the two youngest cohorts (4 to <8 and 8 to <12 years old) were randomly assigned to receive either 2 or 3 mg intranasal glucagon in two separate sessions or to receive a single, weight-based dose of intramuscular glucagon. Participants aged 12 to <17 years received 1 mg intramuscular glucagon in one session and 3 mg intranasal glucagon in the other session. Glucagon was given after glucose was lowered to <80 mg/dL (mean nadir ranged between 67 and 75 mg/dL). RESULTS: All 24 intramuscular and 58 of the 59 intranasal doses produced a >=25 mg/dL rise in glucose from nadir within 20 min of dosing. Times to peak plasma glucose and glucagon levels were similar under both intramuscular and intranasal conditions. Transient nausea occurred in 67% of intramuscular sessions versus 42% of intranasal sessions (P = 0.05); the efficacy and safety of the 2- and 3-mg intranasal doses were similar in the youngest cohorts. CONCLUSIONS: Results of this phase 1, pharmacokinetic, and pharmacodynamic study support the potential efficacy of a needle-free glucagon nasal powder delivery system for treatment of hypoglycemia in youth with type 1 diabetes. Given the similar frequency and transient nature of adverse effects of the 2- and 3-mg intranasal doses in the two youngest cohorts, a single 3-mg intranasal dose appears to be appropriate for use across the entire 4- to <17 year age range. PMID- 26884474 TI - Type 2 Diabetes Genetic Predisposition, Obesity, and All-Cause Mortality Risk in the U.S.: A Multiethnic Analysis. AB - OBJECTIVE: Type 2 diabetes (T2D) is associated with increased mortality in ethnically diverse populations, although the extent to which this association is genetically determined is unknown. We sought to determine whether T2D-related genetic variants predicted all-cause mortality, even after accounting for BMI, in the Third National Health and Nutrition Examination Survey. RESEARCH DESIGN AND METHODS: We modeled mortality risk using a genetic risk score (GRS) from a weighted sum of risk alleles at 38 T2D-related single nucleotide polymorphisms. In age-, sex-, and BMI-adjusted logistic regression models, accounting for the complex survey design, we tested the association with mortality in 6,501 participants. We repeated the analysis within ethnicities (2,528 non-Hispanic white [NHW], 1,979 non-Hispanic black [NHB], and 1,994 Mexican American [MA]) and within BMI categories (<25, 25-30, and >=30 kg/m(2)). Significance was set at P < 0.05. RESULTS: Over 17 years, 1,556 participants died. GRS was associated with mortality risk (OR 1.04 [95% CI 1.00-1.07] per T2D-associated risk allele, P = 0.05). Within ethnicities, GRS was positively associated with mortality risk in NHW and NHB, but not in MA (0.95 [0.90-1.01], P = 0.07). The negative trend in MA was largely driven by those with BMI <25 kg/m(2) (0.91 [0.82-1.00]). In NHW, the positive association was strongest among those with BMI >=30 kg/m(2) (1.07 [1.02 1.12]). CONCLUSIONS: In the U.S., a higher T2D genetic risk was associated with increased mortality risk, especially among obese NHW. The underlying genetic basis for mortality likely involves complex interactions with factors related to ethnicity, T2D, and body weight. PMID- 26884475 TI - The D-amino acid transport by the invertebrate SLC6 transporters KAAT1 and CAATCH1 from Manduca sexta. AB - The ability of the SLC6 family members, the insect neutral amino acid cotransporter KAAT1(K(+)-coupled amino acid transporter 1) and its homologous CAATCH1(cation anion activated amino acid transporter/channel), to transport D amino acids has been investigated through heterologous expression in Xenopus laevis oocytes and electrophysiological techniques. In the presence of D-isomers of leucine, serine, and proline, the msKAAT1 generates inward, transport associated, currents with variable relative potencies, depending on the driving ion Na(+) or K(+). Higher concentrations of D-leucine (>=1 mmol/L) give rise to an anomalous response that suggests the existence of a second binding site with inhibitory action on the transport process. msCAATCH1 is also able to transport the D-amino acids tested, including D-leucine, whereas L-leucine acts as a blocker. A similar behavior is exhibited by the KAAT1 mutant S308T, confirming the relevance of the residue in this position in L-leucine binding and the different interaction of D-leucine with residues involved in transport mechanism. D-leucine and D-serine on various vertebrate orthologs B(0)AT1 (SLC6A19) elicited only a very small current and singular behavior was not observed, indicating that it is specific of the insect neutral amino acid transporters. These findings highlight the relevance of D-amino acid absorption in the insect nutrition and metabolism and may provide new evidences in the molecular transport mechanism of SLC6 family. PMID- 26884476 TI - Angiotensin II stimulates superoxide production by nitric oxide synthase in thick ascending limbs. AB - Angiotensin II (Ang II) causes nitric oxide synthase (NOS) to become a source of superoxide (O2 (-)) via a protein kinase C (PKC)-dependent process in endothelial cells. Ang II stimulates both NO and O2 (-) production in thick ascending limbs. We hypothesized that Ang II causes O2 (-) production by NOS in thick ascending limbs via a PKC-dependent mechanism. NO production was measured in isolated rat thick ascending limbs using DAF-FM, whereas O2 (-) was measured in thick ascending limb suspensions using the lucigenin assay. Consistent stimulation of NO was observed with 1 nmol/L Ang II (P < 0.001; n = 9). This concentration of Ang II-stimulated O2 (-) production by 50% (1.77 +/- 0.26 vs. 2.62 +/- 0.36 relative lights units (RLU)/s/MUg protein; P < 0.04; n = 5). In the presence of the NOS inhibitor L-NAME, Ang II-stimulated O2 (-) decreased from 2.02 +/- 0.29 to 1.10 +/- 0.11 RLU/s/MUg protein (P < 0.01; n = 8). L-arginine alone did not change Ang II-stimulated O2 (-) (2.34 +/- 0.22 vs. 2.29 +/- 0.29 RLU/s/MUg protein; n = 5). In the presence of Ang II plus the PKC alpha/beta1 inhibitor Go 6976, L-NAME had no effect on O2 (-) production (0.78 +/- 0.23 vs. 0.62 +/- 0.11 RLU/s/MUg protein; n = 7). In the presence of Ang II plus apocynin, a NADPH oxidase inhibitor, L-NAME did not change O2 (-) (0.59 +/- 0.04 vs. 0.61 +/- *0.08 RLU/s/MUg protein; n = 5). We conclude that: (1) Ang II causes NOS to produce O2 (-) in thick ascending limbs via a PKC- and NADPH oxidase-dependent process; and (2) the effect of Ang II is not due to limited substrate. PMID- 26884477 TI - Variability in integration of mechanisms associated with high tolerance to progressive reductions in central blood volume: the compensatory reserve. AB - High tolerance to progressive reductions in central blood volume has been associated with higher heart rate (HR), peripheral vascular resistance (PVR), sympathetic nerve activity (SNA), and vagally mediated cardiac baroreflex sensitivity (BRS). Using a database of 116 subjects classified as high tolerance to presyncopal-limited lower body negative pressure (LBNP), we tested the hypothesis that subjects with greater cardiac baroreflex withdrawal (i.e., BRS > 1.0) would demonstrate greater LBNP tolerance associated with higher HR, PVR, and SNA. Subjects underwent LBNP to presyncope. Mean and diastolic arterial pressure (MAP; DAP) was measured by finger photoplethysmography and BRS (down sequence) was autocalculated (WinCPRS) as ?R-R Interval/?DAP. DownBRS : ms/mmHg) was used to dichotomize subjects into two groups (Group 1 = DownBRS > 1.0, N = 49, and Group 2 = DownBRS < 1.0, N = 67) at the time of presyncope. Muscle SNA was measured directly from the peroneal nerve via microneurography (N = 19) in subjects from Groups 1 (n = 9) and 2 (n = 10). Group 1 (DownBRS > 1.0) had lower HR (107 +/- 19 vs. 131 +/- 20 bpm), higher stroke volume (45 +/- 15 vs. 36 +/- 15 mL), less SNA (45 +/- 13 vs. 53 +/- 7 bursts/min), and less increase in PVR (4.1 +/- 1.3 vs. 4.5 +/- 2.6) compared to Group 2 (DownBRS < 1.0). Both groups had similar tolerance times (1849 +/- 260 vs. 1839 +/- 253 sec), MAP (78 +/- 11 vs. 79 +/- 12 mmHg), compensatory reserve index (CRI) (0.10 +/- 0.03 vs. 0.09 +/- 0.01), and cardiac output (4.5 +/- 1.2 vs. 4.7 +/- 1.1 L/min) at presyncope. Contrary to our hypothesis, higher HR, PVR, SNA, and BRS were not associated with greater tolerance to reduced central blood volume. These data are the first to demonstrate the variability and uniqueness of individual human physiological strategies designed to compensate for progressive reductions in central blood volume. The sum total of these integrated strategies is accurately reflected by the measurement of the compensatory reserve. PMID- 26884478 TI - Contrasting effects of afferent and efferent vagal nerve stimulation on insulin secretion and blood glucose regulation. AB - Parasympathetic activation reduces hepatic glucose release and increases pancreatic insulin secretion in hyperglycemic conditions. Thus, vagal nerve stimulation (VNS) may potentially be effective in treating type II diabetes. To investigate this possibility, we hypothesized that VNS reduces blood glucose concentration [Glu] via insulin secretion. [Glu] together with insulin and glucagon serum concentrations were determined in anesthetized rats during baseline conditions and 120 min of cervical VNS with the nerve left intact for combined afferent and efferent VNS (n = 9) or the nerve sectioned proximal or distal from the stimulation electrode for selective efferent (n = 8) or afferent (n = 7) VNS, respectively. Afferent VNS caused a strong and sustained increase in [Glu] (+108.9 +/- 20.9% or +77.6 +/- 15.4%, after 120 min of combined afferent and efferent VNS or selective afferent VNS) that was not accompanied by an increase in serum insulin concentration. However, serum insulin levels increased significantly with selective efferent VNS (+71.2 +/- 27.0% after 120 min of VNS) that increased [Glu] only temporarily (+28.8 +/- 11.7% at 30 min of VNS). Efferent VNS initially increased serum glucagon concentration which remained elevated for 120 min when efferent VNS was combined with afferent VNS, but returned to baseline with selective efferent VNS. These findings demonstrate that afferent VNS causes a marked and sustained increase in [Glu] that is partly mediated by suppression of pancreatic insulin secretion. In contrast, efferent VNS stimulates pancreatic glucagon secretion that appears to be antagonized by insulin secretion in the case of selective efferent VNS. Selective efferent VNS may potentially be effective in treating type II diabetes. PMID- 26884480 TI - Photorhabdus luminescens LN2 requires rpoS for nematicidal activity and nematode development. AB - Photorhabdus (Enterobacteriaceae) bacteria are pathogenic to insects and mutualistic with entomopathogenic Heterorhabditis nematodes. Photorhabdus luminescens subsp. akhurstii LN2, associated with Heterorhabditis indica LN2, shows nematicidal activity against H. bacteriophora H06 infective juveniles (IJs). In the present study, an rpoS mutant of P. luminescens LN2 was generated through allelic exchange to examine the effects of rpoS deletion on the nematicidal activity and nematode development. The results showed that P. luminescens LN2 required rpoS for nematicidal activity against H06 nematodes, normal IJ recovery and development of H. indica LN2, however, not for the bacterial colonization in LN2 and H06 IJs. This provides cues for further understanding the role of rpoS in the mutualistic association between entomopathogenic nematodes and their symbionts. PMID- 26884481 TI - Exposure of Metarhizium acridum mycelium to light induces tolerance to UV-B radiation. AB - Metarhizium acridum is an entomopathogenic fungus commonly used as a bioinsecticide. The conidium is the fungal stage normally employed as field inoculum in biological control programs and must survive under field conditions such as high ultraviolet-B (UV-B) exposure. Light, which is an important stimulus for many fungi, has been shown to induce the production of M. robertsii conidia with increased stress tolerance. Here we show that a two-hour exposure to white or blue/UV-A light of fast-growing mycelium induces tolerance to subsequent UV-B irradiation. Red light, however, does not have the same effect. In addition, we established that this induction can take place with as little as 1 min of white light exposure. This brief illumination scheme could be relevant in future studies of M. acridum photobiology and for the production of UV-B resistant mycelium used in mycelium-based formulations for biological control. PMID- 26884479 TI - Altered cardiorespiratory response to exercise in overweight and obese women with polycystic ovary syndrome. AB - In polycystic ovary syndrome (PCOS), cardiovascular risk is increased. Peak O2 uptake (VO2peak) predicts the cardiovascular risk. We were the first to examine the contribution of systemic O2 delivery and arteriovenous O2 difference to VO2peak in overweight and obese women with PCOS. Fifteen overweight or obese PCOS women and 15 age-, anthropometry-, and physical activity-matched control women performed a maximal incremental cycling exercise test. Alveolar gas exchange (volume turbine and mass spectrometry), arterial O2 saturation (pulse oximetry), and cardiac output (CO) (impedance cardiography) were monitored. Hb concentration was determined. Arterial O2 content and arteriovenous O2 difference (C(a-v)O2) (Fick equation) were calculated. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). PCOS women had lower VO2peak than controls (40 +/- 6 vs. 46 +/- 5 mL/min/kg fat-free mass [FFM], P = 0.011). Arterial O2 content was similarly maintained in the groups throughout the exercise test (P > 0.05). Linear regression analysis revealed a pronounced response of CO to increasing VO2 in PCOS women during the exercise test: A ?CO/?VO2 slope was steeper in PCOS women than in controls (beta = 5.84 vs. beta = 5.21, P = 0.004). Eventually, the groups attained similar peak CO and peak CO scaled to FFM (P > 0.05). Instead, C(a-v)O2 at peak exercise was lower in PCOS women than in controls (13.2 +/- 1.6 vs. 14.8 +/- 2.4 mL O2/100 mL blood, P = 0.044). HOMA-IR was similar in the groups (P > 0.05). The altered cardiorespiratory responses to exercise in overweight and obese PCOS women indicate that PCOS per se is associated with alterations in peripheral adjustments to exercise rather than with limitations of systemic O2 delivery. PMID- 26884482 TI - Melatonin Supports CYP2D-Mediated Serotonin Synthesis in the Brain. AB - Melatonin is used in the therapy of sleep and mood disorders and as a neuroprotective agent. The aim of our study was to demonstrate that melatonin supported (via its deacetylation to 5-methoxytryptamine) CYP2D-mediated synthesis of serotonin from 5-methoxytryptamine. We measured serotonin tissue content in some brain regions (the cortex, hippocampus, nucleus accumbens, striatum, thalamus, hypothalamus, brain stem, medulla oblongata, and cerebellum) (model A), as well as its extracellular concentration in the striatum using an in vivo microdialysis (model B) after melatonin injection (100 mg/kg i.p.) to male Wistar rats. Melatonin increased the tissue concentration of serotonin in the brain structures studied of naive, sham-operated, or serotonergic neurotoxin (5,7 dihydroxytryptamine)-lesioned rats (model A). Intracerebroventricular quinine (a CYP2D inhibitor) prevented the melatonin-induced increase in serotonin concentration. In the presence of pargyline (a monoaminoxidase inhibitor), the effect of melatonin was not visible in the majority of the brain structures studied but could be seen in all of them in 5,7-dihydroxytryptamine-lesioned animals when serotonin storage and synthesis via a classic tryptophan pathway was diminished. Melatonin alone did not significantly increase extracellular serotonin concentration in the striatum of naive rats but raised its content in pargyline-pretreated animals (model B). The CYP2D inhibitor propafenone given intrastructurally prevented the melatonin-induced increase in striatal serotonin in those animals. The obtained results indicate that melatonin supports CYP2D catalyzed serotonin synthesis from 5-methoxytryptamine in the brain in vivo, which closes the serotonin-melatonin-serotonin biochemical cycle. The metabolism of exogenous melatonin to the neurotransmitter serotonin may be regarded as a newly recognized additional component of its pharmacological action. PMID- 26884483 TI - AtPDCD5 Plays a Role in Programmed Cell Death after UV-B Exposure in Arabidopsis. AB - DNA damage responses have evolved to sense and react to DNA damage; the induction of DNA repair mechanisms can lead to genomic restoration or, if the damaged DNA cannot be adequately repaired, to the execution of a cell death program. In this work, we investigated the role of an Arabidopsis (Arabidopsis thaliana) protein, AtPDCD5, which is highly similar to the human PDCD5 protein; it is induced by ultraviolet (UV)-B radiation and participates in programmed cell death in the UV B DNA damage response. Transgenic plants expressing AtPDCD5 fused to GREEN FLUORESCENT PROTEIN indicate that AtPDCD5 is localized both in the nucleus and the cytosol. By use of pdcd5 mutants, we here demonstrate that these plants have an altered antioxidant metabolism and accumulate higher levels of DNA damage after UV-B exposure, similar to levels in ham1ham2 RNA interference transgenic lines with decreased expression of acetyltransferases from the MYST family. By coimmunoprecipitation and pull-down assays, we provide evidence that AtPDCD5 interacts with HAM proteins, suggesting that both proteins participate in the same pathway of DNA damage responses. Plants overexpressing AtPDCD5 show less DNA damage but more cell death in root tips upon UV-B exposure. Finally, we here show that AtPDCD5 also participates in age-induced programmed cell death. Together, the data presented here demonstrate that AtPDCD5 plays an important role during DNA damage responses induced by UV-B radiation in Arabidopsis and also participates in programmed cell death programs. PMID- 26884485 TI - Posttranslational Control of ALA Synthesis Includes GluTR Degradation by Clp Protease and Stabilization by GluTR-Binding Protein. AB - 5-Aminolevulinic acid (ALA) is the first committed substrate of tetrapyrrole biosynthesis and is formed from glutamyl-tRNA by two enzymatic steps. Glutamyl tRNA reductase (GluTR) as the first enzyme of ALA synthesis is encoded by HEMA genes and tightly regulated at the transcriptional and posttranslational levels. Here, we show that the caseinolytic protease (Clp) substrate adaptor ClpS1 and the ClpC1 chaperone as well as the GluTR-binding protein (GBP) interact with the N terminus of GluTR Loss-of function mutants of ClpR2 and ClpC1 proteins show increased GluTR stability, whereas absence of GBP results in decreased GluTR stability. Thus, the Clp protease system and GBP contribute to GluTR accumulation levels, and thereby the rate-limiting ALA synthesis. These findings are supported with Arabidopsis (Arabidopsis thaliana) hema1 mutants expressing a truncated GluTR lacking the 29 N-terminal amino acid residues of the mature protein. Accumulation of this truncated GluTR is higher in dark periods, resulting in increased protochlorophyllide content. It is proposed that the proteolytic activity of Clp protease counteracts GBP binding to assure the appropriate content of GluTR and the adequate ALA synthesis for chlorophyll and heme in higher plants. PMID- 26884484 TI - Suppression of Chloroplastic Alkenal/One Oxidoreductase Represses the Carbon Catabolic Pathway in Arabidopsis Leaves during Night. AB - Lipid-derived reactive carbonyl species (RCS) possess electrophilic moieties and cause oxidative stress by reacting with cellular components. Arabidopsis (Arabidopsis thaliana) has a chloroplast-localized alkenal/one oxidoreductase (AtAOR) for the detoxification of lipid-derived RCS, especially alpha,beta unsaturated carbonyls. In this study, we aimed to evaluate the physiological importance of AtAOR and analyzed AtAOR (aor) mutants, including a transfer DNA knockout, aor (T-DNA), and RNA interference knockdown, aor (RNAi), lines. We found that both aor mutants showed smaller plant sizes than wild-type plants when they were grown under day/night cycle conditions. To elucidate the cause of the aor mutant phenotype, we analyzed the photosynthetic rate and the respiration rate by gas-exchange analysis. Subsequently, we found that both wild-type and aor (RNAi) plants showed similar CO2 assimilation rates; however, the respiration rate was lower in aor (RNAi) than in wild-type plants. Furthermore, we revealed that phosphoenolpyruvate carboxylase activity decreased and starch degradation during the night was suppressed in aor (RNAi). In contrast, the phenotype of aor (RNAi) was rescued when aor (RNAi) plants were grown under constant light conditions. These results indicate that the smaller plant sizes observed in aor mutants grown under day/night cycle conditions were attributable to the decrease in carbon utilization during the night. Here, we propose that the detoxification of lipid-derived RCS by AtAOR in chloroplasts contributes to the protection of dark respiration and supports plant growth during the night. PMID- 26884486 TI - A Medicago truncatula Cystathionine-beta-Synthase-like Domain-Containing Protein Is Required for Rhizobial Infection and Symbiotic Nitrogen Fixation. AB - The symbiosis between leguminous plants and soil rhizobia culminates in the formation of nitrogen-fixing organs called nodules that support plant growth. Two Medicago truncatula Tnt1-insertion mutants were identified that produced small nodules, which were unable to fix nitrogen effectively due to ineffective rhizobial colonization. The gene underlying this phenotype was found to encode a protein containing a putative membrane-localized domain of unknown function (DUF21) and a cystathionine-beta-synthase domain. The cbs1 mutants had defective infection threads that were sometimes devoid of rhizobia and formed small nodules with greatly reduced numbers of symbiosomes. We studied the expression of the gene, designated M truncatula Cystathionine-beta-Synthase-like1 (MtCBS1), using a promoter-beta-glucuronidase gene fusion, which revealed expression in infected root hair cells, developing nodules, and in the invasion zone of mature nodules. An MtCBS1-GFP fusion protein localized itself to the infection thread and symbiosomes. Nodulation factor-induced Ca(2+) responses were observed in the cbs1 mutant, indicating that MtCBS1 acts downstream of nodulation factor signaling. MtCBS1 expression occurred exclusively during Medicago-rhizobium symbiosis. Induction of MtCBS1 expression during symbiosis was found to be dependent on Nodule Inception (NIN), a key transcription factor that controls both rhizobial infection and nodule organogenesis. Interestingly, the closest homolog of MtCBS1, MtCBS2, was specifically induced in mycorrhizal roots, suggesting common infection mechanisms in nodulation and mycorrhization. Related proteins in Arabidopsis have been implicated in cell wall maturation, suggesting a potential role for CBS1 in the formation of the infection thread wall. PMID- 26884487 TI - Singlet Oxygen-Induced Membrane Disruption and Serpin-Protease Balance in Vacuolar-Driven Cell Death. AB - Singlet oxygen plays a role in cellular stress either by providing direct toxicity or through signaling to initiate death programs. It was therefore of interest to examine cell death, as occurs in Arabidopsis, due to differentially localized singlet oxygen photosensitizers. The photosensitizers rose bengal (RB) and acridine orange (AO) were localized to the plasmalemma and vacuole, respectively. Their photoactivation led to cell death as measured by ion leakage. Cell death could be inhibited by the singlet oxygen scavenger histidine in treatments with AO but not with RB In the case of AO treatment, the vacuolar membrane was observed to disintegrate. Concomitantly, a complex was formed between a vacuolar cell-death protease, RESPONSIVE TO DESSICATION-21 and its cognate cytoplasmic protease inhibitor ATSERPIN1. In the case of RB treatment, the tonoplast remained intact and no complex was formed. Over-expression of AtSerpin1 repressed cell death, only under AO photodynamic treatment. Interestingly, acute water stress showed accumulation of singlet oxygen as determined by fluorescence of Singlet Oxygen Sensor Green, by electron paramagnetic resonance spectroscopy and the induction of singlet oxygen marker genes. Cell death by acute water stress was inhibited by the singlet oxygen scavenger histidine and was accompanied by vacuolar collapse and the appearance of serpin-protease complex. Over-expression of AtSerpin1 also attenuated cell death under this mode of cell stress. Thus, acute water stress damage shows parallels to vacuole-mediated cell death where the generation of singlet oxygen may play a role. PMID- 26884489 TI - Implementing the End TB Strategy and the intersection with the Sustainable Development Goals, 2016-2030. PMID- 26884490 TI - The WHO's new End TB Strategy in the post-2015 era of the Sustainable Development Goals. AB - The WHO's new End TB Strategy 2016-2035 has evolved from previous global strategies to respond to old and new challenges and take advantage of new opportunities. It frames the global fight against TB as a development, social justice and human rights issue, while re-emphasizing the public health and clinical fundaments of TB care and prevention. In this commentary, we outline how TB prevention, care and control will both benefit from and contribute to the achievement of the new Sustainable Development Goals that were recently adopted at the United Nations. PMID- 26884488 TI - Arabidopsis MYC Transcription Factors Are the Target of Hormonal Salicylic Acid/Jasmonic Acid Cross Talk in Response to Pieris brassicae Egg Extract. AB - Arabidopsis (Arabidopsis thaliana) plants recognize insect eggs and activate the salicylic acid (SA) pathway. As a consequence, expression of defense genes regulated by the jasmonic acid (JA) pathway is suppressed and larval performance is enhanced. Cross talk between defense signaling pathways is common in plant pathogen interactions, but the molecular mechanism mediating this phenomenon is poorly understood. Here, we demonstrate that egg-induced SA/JA antagonism works independently of the APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor ORA59, which controls the ERF branch of the JA pathway. In addition, treatment with egg extract did not enhance expression or stability of JASMONATE ZIM-domain transcriptional repressors, and SA/JA cross talk did not involve JASMONATE ASSOCIATED MYC2-LIKEs, which are negative regulators of the JA pathway. Investigating the stability of MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that additively control jasmonate-related defense responses, we found that egg extract treatment strongly diminished MYC protein levels in an SA-dependent manner. Furthermore, we identified WRKY75 as a novel and essential factor controlling SA/JA cross talk. These data indicate that insect eggs target the MYC branch of the JA pathway and uncover an unexpected modulation of SA/JA antagonism depending on the biological context in which the SA pathway is activated. PMID- 26884491 TI - A world of cities and the end of TB. AB - The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID- 26884492 TI - Investing to end epidemics: the role of the Global Fund to control TB by 2030. AB - The Global Fund to fight AIDS, Tuberculosis and Malaria provides over three quarters of all international financing towards TB programs with US$4.7 billion disbursed, supporting provision of treatment for 13.2 million patients with smear positive TB and 210 000 patients with multidrug-resistant TB in over 100 countries since 2002. In 2013, the Global Fund launched a new funding model that, among others, is advancing strategic investments to maximize impact, addressing 'missing' TB cases, enhancing a synergistic response to TB/HIV dual epidemics, and building resilient and sustainable systems for health. A new Global Fund Strategy is under development through consultation with various stakeholders, with which the Global Fund will work to play a more catalytic role and foster innovations to end the TB epidemic. PMID- 26884493 TI - Childhood TB: can the End TB Strategy deliver? AB - The accelerated reductions in global TB incidence required to achieve the End TB Strategy goal will result in reductions in the burden of childhood TB. Contact screening and preventive therapy have emerged as important components of TB burden reduction, and family-centered approaches could be an effective route in delivering these activities. Lack of accurate diagnostics for children remains a critical barrier and a need remains for better collaborative and supportive links between the child health and TB control sectors. Irrespective of whether the ambitious targets can be achieved, the unprecedented opportunities provided by the End TB Strategy must be embraced. PMID- 26884494 TI - TB control: challenges and opportunities for India. AB - India's TB control programme has treated over 19 million patients, but the incidence of TB continues to be high. TB is a major killer and drug-resistant TB is a growing threat. There are several likely reasons, including social conditions and co-morbidities that fuel the TB epidemic: under-investment by the government, weak programme implementation and management, suboptimal quality of care in the private sector, and insufficient advocacy around TB. Fortunately, India possesses the technical know-how, competence and resources to address these challenges. The End TB Strategy by WHO offers India an excellent blueprint to advance the agenda of TB control. PMID- 26884495 TI - Can China achieve the WHO global targets for TB control by 2035? AB - To reach the ambitious WHO TB global targets by 2035, it is likely that China will need a comprehensive strategy that builds on its existing high-quality directly observed treatment, short-course program. This will require optimizing the use of existing tools within a changing health system landscape. In addition, new tools are needed to identify and treat TB in high-risk groups and in older people, who are a growing driver of disease incidence. Lastly, strategies are needed to address the proximate risk factors and social determinants that underlie trends in TB burden. PMID- 26884496 TI - Management of multidrug-resistant TB: novel treatments and their expansion to low resource settings. AB - Despite overall progress in global TB control, the rising burden of multidrug resistant TB (MDR-TB) threatens to undermine efforts to end the worldwide epidemic. Of the 27 countries classified as high burden for MDR-TB, 17 are in 'low' or 'low-middle' income countries. Shorter, all oral and less toxic multidrug combinations are required to improve treatment outcomes in these settings. Suitability for safe co-administration with HIV drugs is also desirable. A range of strategies and several new drugs (including bedaquiline, delamanid and linezolid) are currently undergoing advanced clinical evaluations to define their roles in achieving these aims. However, several clinical questions and logistical challenges need to be overcome before these new MDR-TB treatments fulfil their potential. PMID- 26884497 TI - Addressing diabetes mellitus as part of the strategy for ending TB. AB - As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID- 26884498 TI - Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications. AB - TB is the leading cause of HIV/AIDS-related deaths globally. New diagnostic tools are urgently needed to avert deaths from undiagnosed HIV-associated TB. Although simple assays that detect lipoarabinomannan (LAM) in urine have been commercially available for years, their specific role and utility were initially misunderstood, such that they have been slower to emerge from the diagnostics pipeline than otherwise might have been expected. In this article, we review and explain how urine-LAM assays should be understood as diagnostics for disseminated TB in HIV-positive patients with advanced immunodeficiency, in whom haematogenous TB dissemination to the kidneys serves as the primary mechanism by which LAM enters the urine. These insights are critical for the appropriate design of studies to evaluate these assays and to understand how they might be most usefully implemented. This understanding also supports the 2015 WHO recommendations on the restricted use of these assays in sick HIV-positive patients with advanced immunodeficiency. PMID- 26884499 TI - Drug-resistant TB: deadly, costly and in need of a vaccine. AB - TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9-25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be 'resistant' to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035. PMID- 26884500 TI - Alternative medicine: an ethnographic study of how practitioners of Indian medical systems manage TB in Mumbai. AB - BACKGROUND: Mumbai is a hot spot for drug-resistant TB, and private practitioners trained in AYUSH systems (Ayurveda, yoga, Unani, Siddha and homeopathy) are major healthcare providers. It is important to understand how AYUSH practitioners manage patients with TB or presumptive TB. METHODS: We conducted semi-structured interviews of 175 Mumbai slum-based practitioners holding degrees in Ayurveda, homeopathy and Unani. Most providers gave multiple interviews. We observed 10 providers in clinical interactions, documenting: clinical examinations, symptoms, history taking, prescriptions and diagnostic tests. RESULTS: No practitioners exclusively used his or her system of training. The practice of biomedicine is frequent, with practitioners often using biomedical disease categories and diagnostics. The use of homeopathy was rare (only 4% of consultations with homeopaths resulted in homeopathic remedies) and Ayurveda rarer (3% of consultations). For TB, all mentioned chest x-ray while 31 (17.7%) mentioned sputum smear as a TB test. One hundred and sixty-four practitioners (93.7%) reported referring TB patients to a public hospital or chest physician. Eleven practitioners (6.3%) reported treating patients with TB. Nine (5.1%) reported treating patients with drug-susceptible TB with at least one second-line drug. CONCLUSIONS: Important sources of health care in Mumbai's slums, AYUSH physicians frequently use biomedical therapies and most refer patients with TB to chest physicians or the public sector. They are integral to TB care and control. PMID- 26884501 TI - Effectiveness of a conditional cash transfer programme on TB cure rate: a retrospective cohort study in Brazil. AB - BACKGROUND: Despite the efforts of the National Tuberculosis Programme, TB cure rates in Brazil are sub-optimal. The End TB Strategy for post-2015 identifies conditional cash transfer interventions as powerful tools to improve TB control indicators, including TB cure rate. This study aims to inform the new policy by evaluating the role of the Bolsa Familia Programme (BFP), one of the largest conditional cash transfer programmes in the world, on TB cure rates in Brazil. METHODS: We undertook a retrospective cohort study, based on an unprecedented record linkage of socioeconomic and health data, to compare cases of patients newly diagnosed with TB in 2010 receiving BFP cash benefits (n=5788) with those who did not (n=1467) during TB treatment. We used Poisson regression with robust variance to estimate the relative risks for TB cure adjusted for known confounders. RESULTS: The cure rate among patients exposed to BFP during TB treatment was 82.1% (4752/5788), 5.2% higher than among those not exposed. This was confirmed after controlling for TB type, diabetes mellitus, HIV status and other relevant clinical and socioeconomic covariates (RR=1.07, 95% CI 1.04 to 1.11 for cure rates among BFP beneficiaries). This association seemed higher for patients not under directly observed treatment (RR=1.11; 95% CI 1.05 to 1.16). CONCLUSIONS: Although further research is needed, this study suggests that conditional cash transfer programmes can contribute to improve TB cure rate in Brazil. PMID- 26884505 TI - THE ABSORPTION PROPERTIES OF LEAD-FREE GARMENTS FOR USE IN RADIATION PROTECTION. AB - In this study, the absorption capability and the weight of various radiation shielding materials were evaluated, for applications as alternatives to lead garments. Toxicity, atomic number, density, K-edge absorption energy and availability of elements that can serve as an alternative to lead, including tin, antimony, bismuth and tungsten, were considered. The attenuation coefficients of these elements were determined using the XCOM software package, and these metals were mixed with polymers at 50, 70, 80 and 85 % mass ratios. It can be concluded that all of the new shielding materials used in the study can be used for a diagnostic range of X-rays. However, they were compared with the commercial lead garments in terms of weight and attenuation coefficient; the 85 % samples were lighter than a 0.5-mm lead garment and provided superior radiation protection, which demonstrates its potential for commercial applications. PMID- 26884503 TI - Child Physical Activity Associations With Cardiovascular Risk Factors Differ by Race. AB - PURPOSE: The objective of this study was to characterize the relationship between objectively-measured physical activity (PA) and cardiovascular risk factors in 7 year-old children and test the hypothesis that it differs by race. METHODS: Cross sectional study of 308 7-year-old children drawn from a major US metropolitan community. PA (moderate-to-vigorous, MVPA; light, LPA; and inactivity, IA) was measured by accelerometry (RT3). Cardiovascular risk factors included BMI, blood pressure, and serum lipids, glucose and insulin concentrations. General linear modeling was used to evaluate the independent associations between PA measures and cardiovascular risk factors and interactions by race. RESULTS: In black children, greater time spent in PA was independently associated with lower levels of triglycerides (MVPA and LPA, both p < .01), glucose (MVPA, p < .05), and insulin (MVPA, p < .01); these associations were not evident in white children. Across races, greater inactivity was independently associated with greater low density lipoprotein cholesterol in overweight participants (p < .01) but not in normal weight participants. No PA measure was associated with BMI, systolic blood pressure, or high-density lipoprotein cholesterol. CONCLUSIONS: In this cohort of 7-year-old children, the relationship between PA and some cardiovascular risk factors differed by race. These findings may have implications for targeting of PA promotion efforts in children. PMID- 26884506 TI - Influence of Exercise and Training on Critical Stages of Bone Growth and Development. AB - Although osteoporosis is considered a geriatric disease, factors affecting bone strength are most influential during child growth and development. This article reviews what is known and still unclear in terms of bone growth, development and adaptation relative to physical activity before and during puberty. Bone is responsive to certain exercise protocols early in puberty and less so in postpubertal years, where bone strength, rather than bone mass, being the outcome of interest. Mechanical loading and high impact exercise promote bone strength. Intense training before and during puberty, however, may negatively affect bone development. Future research should focus on increasing our mechanistic understanding of the manner by which diverse physical stressors alter the integrity of bone. Longitudinal studies that examine the extent to which muscle and bone are comodulated by growth in children are also recommended. PMID- 26884502 TI - Macrophage polarization in response to oral commensals and pathogens. AB - Macrophages have been identified in the periodontium. Data have phenotypically described these cells, demonstrated changes with progressing periodontal disease, and identified their ability to function in antigen-presentation critical for adaptive immune responses to individual oral bacterium. Recent evidence has emphasized an important role for the plasticity of macrophage phenotypes, not only in the resulting function of these cells in various tissues, but also clear differences in the stimulatory signals that result in M1 (classical activation, inflammatory) and M2 (alternative activation/deactivated, immunomodulatory) cells. This investigation hypothesized that the oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans induce M1-type cells, while oral commensal bacteria primarily elicit macrophage functions consistent with an M2 phenotype. However, we observed that the M1 output from P. gingivalis challenge, showed exaggerated levels of pro-inflammatory cytokines, with a much lower production of chemokines related to T-cell recruitment. This contrasted with A. actinomycetemcomitans infection that increased both the pro-inflammatory cytokines and T-cell chemokines. Thus, it appears that P. gingivalis, as an oral pathogen, may have a unique capacity to alter the programming of the M1 macrophage resulting in a hyperinflammatory environment and minimizing the ability for T-cell immunomodulatory influx into the lesions. PMID- 26884507 TI - Deubiquitylation of Protein Cargo Is Not an Essential Step in Exosome Formation. AB - Exosomes, derived from multivesicular bodies (MVBs), contain proteins and genetic materials from their cell of origin and are secreted from various cells types, including kidney epithelial cells. In general, it is thought that protein cargo is ubiquitylated but that ubiquitin is cleaved by specific deubiquitylases during the process of cargo incorporation into MVBs. Here, we provide direct evidence that, in vivo, deubiquitylation is not essential. Ubiquitin was detected within human MVBs and urinary exosomes by electron microscopy. Of the >6000 proteins identified in human urinary exosomes was mass spectrometry, 15% were ubiquitylated with various topologies (Lys63>Lys48> Lys11>Lys6>Lys29>Lys33>Lys27). A significant preference for basic amino acids upstream of ubiquitylation sites suggests specific ubiquitylation motifs. The current studies demonstrate that, in vivo, deubiquitylation of proteins is not necessary for their incorporation into MVBs and highlight that urinary exosomes are an enriched source for studying ubiquitin modifications in physiological or disease states. PMID- 26884509 TI - Alcohol Consumption in Vietnam, and the Use of 'Standard Drinks' to Measure Alcohol Intake. AB - AIMS: To provide nationally representative data on alcohol consumption in Vietnam and to assess whether reported numbers of 'standard drinks' consumed have evidence of validity (particularly in rural areas where home-made alcohol is consumed from cups of varying size). METHODS: A nationally representative population-based survey of 14,706 participants (46.5% males, response proportion 64.1%) aged 25-64 years in Vietnam. Measurements were made in accordance with WHO STEPS protocols. Data were analysed using complex survey methods. RESULTS: Among men, 80% reported drinking alcohol during the last year, and 40% were hazardous/harmful drinkers. Approximately 60% of men and <5% of women had consumed alcohol during the last week, with one-in-four of the men reporting having consumed at least five standard drinks on at least one occasion. Numbers of standard drinks reported by men were associated with blood pressure/hypertension, particularly in rural areas (P < 0.001 for trend). Most of the calibration and discrimination possible from self-reported information on alcohol consumption was provided by binary responses to questions on whether or not alcohol had been consumed during the reference period. CONCLUSION: Alcohol use and harmful consumption were common among Vietnamese men but less pronounced than in Western nations. Self-reports of quantity of alcohol consumed in terms of standard drinks had predictive validity for blood pressure and hypertension even in rural areas. However, using detailed measures of consumption resulted in only minor improvements in prediction compared to simple measures. PMID- 26884508 TI - Harms to Adults from Others' Heavy Drinking in Five Indian States. AB - AIMS: The aims of this study were to assess a wide range of alcohol-related harms from known heavy drinkers in Indian respondents' lives, and to assess respondents' characteristics and drinking patterns associated with reporting these harms. METHODS: Household interviews were administered in five Indian states from October 2011 to May 2012. For the secondary data analyses in this study, participants were Indians, ages 15-70, who self-reported having a heavy drinker in their lives (n = 5,375). We assessed the proportion of respondents reporting seventeen types of alcohol-related harms from a heavy drinker. RESULTS: Approximately 83% of respondents reported at least one alcohol-related harm from a heavy drinker in their lives. Twenty-five percent of respondents reported physical harm, 6% reported sexual harm and 50% reported emotional harm or neglect. Controlling for other factors, being in the upper income quartiles was associated with reporting >=5 harm types. Among females, being age 25-39 and married/cohabitating predicted reporting >=5 harm types, while among males, being age 25-39 or age 40-70 and living in a rural area increased the odds. Among females, binge drinkers had 46% lower odds of reporting >=5 harm types than abstainers; among males, binge drinkers had 54% greater odds. CONCLUSION: Regardless of respondents' own drinking pattern, a substantial proportion of respondents reported experiencing a range of harms from a known heavy drinker; interventions are needed to reduce these harms. PMID- 26884510 TI - The expert patient. PMID- 26884513 TI - If you had to choose 1 article to read this month .... PMID- 26884511 TI - Global Protein Oxidation Profiling Suggests Efficient Mitochondrial Proteome Homeostasis During Aging. AB - The free radical theory of aging is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Because themajority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the aging model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidized and nonoxidized protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidized. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during aging as long as protein de novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged and undamaged protein species. These findings contradict a massive increase in protein oxidation during aging and rather suggest a protein damage homeostasis mechanism even at late age. PMID- 26884515 TI - Do informal social connections among patients in a practice contribute to effective care? PMID- 26884512 TI - The role of pollinators in the evolution of corolla shape variation, disparity and integration in a highly diversified plant family with a conserved floral bauplan. AB - BACKGROUND AND AIMS: Brassicaceae is one of the most diversified families in the angiosperms. However, most species from this family exhibit a very similar floral bauplan. In this study, we explore the Brassicaceae floral morphospace, examining how corolla shape variation (an estimation of developmental robustness), integration and disparity vary among phylogenetically related species. Our aim is to check whether these floral attributes have evolved in this family despite its apparent morphological conservation, and to test the role of pollinators in driving this evolution. METHODS: Using geometric morphometric tools, we calculated the phenotypic variation, disparity and integration of the corolla shape of 111 Brassicaceae taxa. We subsequently inferred the phylogenetic relationships of these taxa and explored the evolutionary lability of corolla shape. Finally, we sampled the pollinator assemblages of every taxon included in this study, and determined their pollination niches using a modularity algorithm. We explore the relationship between pollination niche and the attributes of corolla shape. KEY RESULTS: Phylogenetic signal was weak for all corolla shape attributes. All taxa had generalized pollination systems. Nevertheless, they belong to different pollination niches. There were significant differences in corolla shape among pollination niches even after controlling for the phylogenetic relationship of the plant taxa. Corolla shape variation and disparity was significantly higher in those taxa visited mostly by nocturnal moths, indicating that this pollination niche is associated with a lack of developmental robustness. Corolla integration was higher in those taxa visited mostly by hovering long-tongued flies and long-tongued large bees. CONCLUSIONS: Corolla variation, integration and disparity were evolutionarily labile and evolved very recently in the evolutionary history of the Brassicaceae. These floral attributes were strongly related to the pollination niche. Even in a plant clade having a very generalized pollination system and exhibiting a conserved floral bauplan, pollinators can drive the evolution of important developmental attributes of corolla shape. PMID- 26884517 TI - Physician-assisted suicide from a patient's perspective. PMID- 26884516 TI - Rationale and model for integrating the pharmacist into the outpatient referral consultation process. PMID- 26884518 TI - Improving primary care: Continuity is about relationships. PMID- 26884519 TI - Dangerous ideas: Top 4 proposals presented at Family Medicine Forum. PMID- 26884521 TI - Where is family medicine heading? PMID- 26884522 TI - Be responsive to needs of patients and communities. PMID- 26884523 TI - Is family medicine ready to look where it is heading? PMID- 26884524 TI - Responsibility and professionalism in family medicine. PMID- 26884526 TI - Update on age-appropriate preventive measures and screening for Canadian primary care providers. AB - OBJECTIVE: To summarize the best available age-appropriate, evidence-based guidelines for prevention and screening in Canadian adults. QUALITY OF EVIDENCE: The Canadian Task Force on Preventive Health Care recommendations are the primary source of information, supplemented by relevant US Preventive Services Task Force recommendations when a Canadian task force guideline was unavailable or outdated. Leading national disease-specific or specialty-specific organizations' guidelines were also reviewed to ensure the most up-to-date evidence was included. MAIN MESSAGE: Recommended screening maneuvers by age and sex are presented in a summary table highlighting the quality of evidence supporting these recommendations. An example of a template for use with electronic medical records or paper-based charts is presented. CONCLUSION: Whether primary care providers use a dedicated preventive health visit or opportunistic preventive counseling and screening in their patient encounters, this summary of evidence-based recommendations can help maximize efficiency and prevent important omissions and unnecessary screening. PMID- 26884527 TI - Two cases of methemoglobinemia: In a military community hospital. PMID- 26884529 TI - Unfortunate synergy between HIV and genital herpes. PMID- 26884528 TI - Ginger for nausea and vomiting of pregnancy. AB - Clinical questionCan ginger treat nausea and vomiting of pregnancy?Bottom lineIn the first trimester ginger might improve nausea and vomiting by about 4 points on a 40-point scale or stop vomiting for 1 in 3 women at 6 days. The largest study suggests no increase in fetal malformations or stillbirths, but smaller studies suggest otherwise. PMID- 26884530 TI - Real-life research: 6for6 and rural family practice. PMID- 26884531 TI - The Bellelli Family: Degas and family medicine. PMID- 26884532 TI - Assessment of professionalism in family medicine residents: Turning the mirror around. PMID- 26884535 TI - Rural taskforce update. PMID- 26884543 TI - Neural basis of processing threatening voices in a crowded auditory world. AB - In real world situations, we typically listen to voice prosody against a background crowded with auditory stimuli. Voices and background can both contain behaviorally relevant features and both can be selectively in the focus of attention. Adequate responses to threat-related voices under such conditions require that the brain unmixes reciprocally masked features depending on variable cognitive resources. It is unknown which brain systems instantiate the extraction of behaviorally relevant prosodic features under varying combinations of prosody valence, auditory background complexity and attentional focus. Here, we used event-related functional magnetic resonance imaging to investigate the effects of high background sound complexity and attentional focus on brain activation to angry and neutral prosody in humans. Results show that prosody effects in mid superior temporal cortex were gated by background complexity but not attention, while prosody effects in the amygdala and anterior superior temporal cortex were gated by attention but not background complexity, suggesting distinct emotional prosody processing limitations in different regions. Crucially, if attention was focused on the highly complex background, the differential processing of emotional prosody was prevented in all brain regions, suggesting that in a distracting, complex auditory world even threatening voices may go unnoticed. PMID- 26884544 TI - Are batterers different from other criminals? An fMRI study. AB - Intimate partner violence (IPV) is a complex and global phenomenon that requires a multi-perspective analysis. Nevertheless, the number of neuroscientific studies conducted on this issue is scarce as compared with studies of other types of violence, and no neuroimaging studies comparing batterers to other criminals have been conducted. Thus, the main aim of this study was to compare the brain functioning of batterers to that of other criminals when they are exposed to IPV or general violence pictures. An fMRI study was conducted in 21 batterers and 20 other criminals while they observed IPV images (IPVI), general violence images (GVI) and neutral images (NI). Results demonstrated that batterers, compared with other criminals, exhibited a higher activation in the anterior and posterior cingulate cortex and in the middle prefrontal cortex and a decreased activation in the superior prefrontal cortex to IPVI compared to NI. The paired t-test comparison between IPVI and GVI for each group showed engagement of the medial prefrontal cortex, the posterior cingulate and the left angular cortices to IPVI in the batterer group only. These results could have important implications for a better understanding of the IPV phenomenon. PMID- 26884545 TI - Habenula responses to potential and actual loss in major depression: preliminary evidence for lateralized dysfunction. AB - The habenula has been implicated in predicting negative events and in responding to unexpected negative outcomes. Animal models of depression have supported the hypothesis that perturbations in habenula activity contribute to the pathophysiology of Major Depressive Disorder (MDD), a psychiatric illness characterized by abnormalities in responding to negative feedback and by pessimism in evaluating the likelihood of future events. No research to date, however, has examined human habenula responses to potential and experienced negative outcomes in MDD. In this study, depressed and healthy control participants performed a probabilistic guessing task for monetary rewards and penalties during high-resolution functional magnetic resonance imaging of the habenula. In healthy adults, we observed a pattern of habenula activation consistent with its hypothesized role in predicting future losses and responding to suboptimal outcomes. In contrast, in depressed participants the left habenula was not activated significantly during the prediction or experience of monetary penalty. Complementing this group difference, attenuated habenula activation to negative feedback in control participants was associated with levels of shame and rumination. The results of this study suggest that depressed individuals are characterized by dysfunction in a neural system involved in generating expectations and comparing expectations with objective outcomes. PMID- 26884546 TI - Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms. AB - Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms. PMID- 26884547 TI - Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. AB - Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs. PMID- 26884549 TI - The Similarity and Appropriate Usage of Three Honey Bee (Hymenoptera: Apidae) Datasets for Longitudinal Studies. AB - Honey bee (Apis mellifera L., Hymenoptera: Apidae) colonies have experienced profound fluctuations, especially declines, in the past few decades. Long-term datasets on honey bees are needed to identify the most important environmental and cultural factors associated with these changes. While a few such datasets exist, scientists have been hesitant to use some of these due to perceived shortcomings in the data. We compared data and trends for three datasets. Two come from the US Department of Agriculture's National Agricultural Statistics Service (NASS), Agricultural Statistics Board: one is the annual survey of honey producing colonies from the Annual Bee and Honey program (ABH), and the other is colony counts from the Census of Agriculture conducted every five years. The third dataset we developed from the number of colonies registered annually by some states. We compared the long-term patterns of change in colony numbers among the datasets on a state-by-state basis. The three datasets often showed similar hive numbers and trends varied by state, with differences between datasets being greatest for those states receiving a large number of migratory colonies. Dataset comparisons provide a method to estimate the number of colonies in a state used for pollination versus honey production. Some states also had separate data for local and migratory colonies, allowing one to determine whether the migratory colonies were typically used for pollination or honey production. The Census of Agriculture should provide the most accurate long-term data on colony numbers, but only every five years. PMID- 26884548 TI - Paranoid Ideation and Violence: Meta-analysis of Individual Subject Data of 7 Population Surveys. AB - There is controversy whether associations between psychosis and violence are due to coexisting substance misuse and factors increasing risk in nonpsychotic persons. Recent studies in clinical samples have implicated independent effects of paranoid delusions. Research findings suggest that individual psychotic-like experiences on the psychosis continuum in the general population are associated with violence; it remains unclear whether this association is due to psychiatric comorbidity. We pooled data from 7 UK general population surveys (n = 23 444) and conducted a meta-analysis of individual subject data. Further meta-analyses were performed to identify heterogeneity. Main exposure variables: 5 psychotic-like experiences and a categorical measure of psychosis. Comorbidity was established through standardized self-report instruments. Information was collected on violence, severity, victims. Paranoid ideation was associated with violence (AOR 2.26, 95% CI 1.75-2.91), severity and frequency, even when controlling for effects of other psychotic-like-experiences. Associations were not explained by comorbid conditions, including substance dependence. Psychotic disorder was associated with violence and injury to the perpetrator but associations were explained by paranoid ideation. Individual associations between hypomania, thought insertion, hallucinations, and violence were nonsignificant after adjustments, and significantly associated only when comorbid with antisocial personality disorder. Strange experiences were only associated with intimate partner violence. Paranoid ideation on a psychosis-continuum in the general population was associated with violence. All other associations were explained by comorbidity. Further investigation should determine whether paranoid ideation among persons in the community require preventive interventions, similar to those presenting to mental health services. Nevertheless, risks are considerably increased for psychotic-like-experiences with co-occurring antisocial personality disorder. PMID- 26884550 TI - Adolescent sexual health: time to invest in a healthy future generation. PMID- 26884551 TI - Potential value of EUS in pancreatic surveillance of VHL patients. AB - BACKGROUND: Patients with von Hippel-Lindau (VHL) disease are prone to develop pancreatic neuroendocrine tumors (pNETs). However, the best imaging technique for early detection of pNETs in VHL is currently unknown. In a head-to-head comparison, we evaluated endoscopic ultrasound (EUS) and (11)C-5 hydroxytryptophan positron emission tomography ((11)C-5-HTP PET) compared with conventional screening techniques for early detection of pancreatic solid lesions in VHL patients. METHODS: We conducted a cross-sectional, prospective study in 22 patients at a tertiary care university medical center. Patients with VHL mutation or with one VHL manifestation and a mutation carrier as first-degree family member, with recent screening by abdominal computed tomography (CT) or magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS), were eligible. Patients underwent EUS by linear Pentax echoendoscope and Hitachi EUB 525, and (11)C-5-HTP PET. Patient-based and lesion-based positivity for pancreatic solid lesions were calculated for all imaging techniques with a composite reference standard. RESULTS: In 10 of the 22 patients, 20 pancreatic solid lesions were detected: 17 with EUS (P < 0.05 vs CT/MRI+ SRS), 3 with (11)C 5-HTP PET, 3 with SRS, 9 with CT/MRI, and 9 with CT/MRI + SRS. EUS evaluations showed solid lesions with a median size of 9.7 mm (range 2.9-55 mm) and most of them were homogeneous, hypoechoic, isoelastic, and hypervascular. Moreover, EUS detected multiple pancreatic cysts in 18 patients with a median of 4 cysts (range 1-30). CONCLUSIONS: EUS is superior to CT/MRI + SRS for detecting pancreatic solid lesions in VHL disease.(11)C-5-HTP PET has no value as a screening method in this setting. EUS performs well in early detection of pNETs, but its role in VHL surveillance is unclear. PMID- 26884553 TI - Proposed Staging System for Patients With HPV-Related Oropharyngeal Cancer Based on Nasopharyngeal Cancer N Categories. AB - PURPOSE: Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC. PATIENTS AND METHODS: Patients with newly diagnosed HPV-positive OPC (by p16 immunohistochemistry or in situ hybridization) treated at our institution from January 2003 through December 2012 were included. By using recursive partitioning analysis (RPA), we developed new stage groupings with both traditional OPC regional lymph node (N) categories and nasopharyngeal carcinoma (NPC) N categories. Survival was estimated by the Kaplan Meier method, and the relationship between stage and survival was examined by using Cox proportional hazards regression analysis. RESULTS: A total of 661 patients with HPV-positive OPC met the inclusion criteria. With the traditional TNM staging system, there was no difference in survival between stages (P = .141). RPA with NPC N categories resulted in more balanced stage groups and better separation between groups for 5-year survival than RPA with traditional OPC N categories. With the stage groupings that were based in part on NPC N categories, the risk of death increased with increasing stage (P for trend < .001), and patients with stage III disease had five times the risk of death versus patients with stage IA disease. CONCLUSION: New stage groupings that are based on primary tumor (T) categories and NPC N categories better separate patients with HPV-positive OPC with respect to survival than does the current AJCC/UICC TNM staging system. Although confirmation of our findings in other patient populations is needed, we propose consideration of NPC N categories as an alternative to the traditional OPC N categories in the new AJCC/UICC TNM staging system that is currently being developed. PMID- 26884552 TI - Mechanisms of oestrogen receptor (ER) gene regulation in breast cancer. AB - Most breast cancers are driven by a transcription factor called oestrogen receptor (ER). Understanding the mechanisms of ER activity in breast cancer has been a major research interest and recent genomic advances have revealed extraordinary insights into how ER mediates gene transcription and what occurs during endocrine resistance. This review discusses our current understanding on ER activity, with an emphasis on several evolving, but important areas of ER biology. PMID- 26884554 TI - Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole. AB - PURPOSE: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. PATIENTS AND METHODS: Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for >= 1 year were treated with letrozole (2.5 mg) daily for >= 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. RESULTS: The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naive patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. CONCLUSION: These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients. PMID- 26884555 TI - Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial. AB - PURPOSE: Alisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population. PATIENTS AND METHODS: Patients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m(2) per day on days 1 to 7 along with irinotecan 50 mg/m(2) intravenously and temozolomide 100 mg/m(2) orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained. RESULTS: Twenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m(2), with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib. CONCLUSION: Alisertib 60 mg/m(2) per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing. PMID- 26884556 TI - "It Is What It Is". PMID- 26884557 TI - Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. AB - PURPOSE: Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA. PATIENTS AND METHODS: In a multicenter, open-label, phase III trial, elderly patients >= 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS <= 1 and age <= 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life. RESULTS: Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007). CONCLUSION: In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity. PMID- 26884558 TI - Accuracy of Adverse Event Ascertainment in Clinical Trials for Pediatric Acute Myeloid Leukemia. AB - PURPOSE: Reporting of adverse events (AEs) in clinical trials is critical to understanding treatment safety, but data on AE accuracy are limited. This study sought to determine the accuracy of AE reporting for pediatric acute myeloid leukemia clinical trials and to test whether an external electronic data source can improve reporting. METHODS: Reported AEs were evaluated on two trials, Children's Oncology Group AAML03P1 and AAML0531 arm B, with identical chemotherapy regimens but with different toxicity reporting requirements. Chart review for 12 AEs for patients enrolled in AAML0531 at 14 hospitals was the gold standard. The sensitivity and positive predictive values (PPV) of the AAML0531 AE report and AEs detected by review of Pediatric Health Information System (PHIS) billing and microbiology data were compared with chart data. RESULTS: Select AE rates from AAML03P1 and AAML0531 arm B differed significantly and correlated with the targeted toxicities of each trial. Chart abstraction was performed on 204 patients (758 courses) on AAML0531. AE report sensitivity was < 50% for eight AEs, but PPV was > 75% for six AEs. AE reports for viridans group streptococcal bacteremia, a targeted toxicity on AAML0531, had a sensitivity of 78.3% and PPV of 98.1%. PHIS billing data had higher sensitivity (> 50% for nine AEs), but lower PPV (< 75% for 10 AEs). Viridans group streptococcal detection using PHIS microbiology data had high sensitivity (92.3%) and PPV (97.3%). CONCLUSION: The current system of AE reporting for cooperative oncology group clinical trials in pediatric acute myeloid leukemia underestimates AE rates. The high sensitivity and PPV of PHIS microbiology data suggest that using external data sources may improve the accuracy of AE reporting. PMID- 26884559 TI - Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study. AB - PURPOSE: The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. PATIENTS AND METHODS: The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2 year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. RESULTS: In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2 negative patients. CONCLUSION: Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. PMID- 26884561 TI - White Knuckling. PMID- 26884560 TI - Trends in Health-Related Quality of Life After a Diagnosis of Ductal Carcinoma In Situ. AB - PURPOSE: Studies of quality of life (QoL) are scarce among survivors of ductal carcinoma in situ (DCIS). The objective of this study was to assess long-term QoL in DCIS survivors in relation to age at diagnosis, time since diagnosis, and treatments received. METHODS: We assessed physical and mental measures of health related QoL in 1,604 patients with DCIS diagnosed in 1997 to 2006 with up to four follow-up interviews. We further compared baseline QoL to 1,055 control patients without DCIS. QoL was measured using the validated Medical Outcomes Study Short Form 36 Health Status Survey questionnaire. Among patients with DCIS, we examined trends in QoL over time since diagnosis using generalized linear regression models, adjusting for confounders. We tested for effect modification by surgical treatment choice, post-treatment endocrine therapy use, and age at diagnosis. RESULTS: Both physical and mental measures of QoL among DCIS survivors at fewer than 2 years after diagnosis were comparable to controls. Mental measures of QoL among patients with DCIS declined at >= 10 years after diagnosis and were significantly lower than at less than 2 years after diagnosis (47.4 v 52.0; P < .01). In the first 5 years after a DCIS diagnosis, mental QoL was significantly higher among women diagnosed at ages 50 to 74 years compared with those diagnosed at ages 28 to 49 years, although this difference was not sustained in later time periods. CONCLUSION: QoL after a DCIS diagnosis was generally comparable to that of women of similar age without a personal history of DCIS. Our findings suggest that DCIS survivors, and particularly those diagnosed at a younger age, may benefit from support for mental QoL. PMID- 26884563 TI - Toward Minimizing Overtreatment and Undertreatment of Ductal Carcinoma In Situ in the United States. PMID- 26884562 TI - Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study. AB - PURPOSE: CHEK2 is a cell cycle checkpoint regulator, and the CHEK2*1100delC germline mutation leads to loss of function and increased breast cancer risk. It seems plausible that this mutation could also predispose to other cancers. Therefore, we tested the hypothesis that CHEK2*1100delC heterozygosity is associated with increased risk for other cancers in addition to breast cancer in the general population. PATIENTS AND METHODS: We examined 86,975 individuals from the Copenhagen General Population Study, recruited from 2003 through 2010. The participants completed a questionnaire on health and lifestyle, were examined physically, had blood drawn for DNA extraction, were tested for presence of CHEK2*1100delC using Taqman assays and sequencing, and were linked over 1943 through 2011 to the Danish Cancer Registry. Incidences and risks of individual cancer types, including breast cancer, were calculated using Kaplan-Meier estimates, Fine and Gray competing-risks regressions, and stratified analyses with interaction tests. RESULTS: Among 86,975 individuals, 670 (0.8%) were CHEK2*1100delC heterozygous, 2,442 developed breast cancer, and 6,635 developed other cancers. The age- and sex-adjusted hazard ratio for CHEK2*1100delC heterozygotes compared with noncarriers was 2.08 (95% CI, 1.51 to 2.85) for breast cancer and 1.45 (95% CI, 1.15 to 1.82) for other cancers. When stratifying for sex, the age-adjusted hazard ratios for other cancers were 1.54 (95% CI, 1.08 to 2.18) for women and 1.37 (95% CI, 1.01 to 1.85) for men (sex difference: P = .63). For CHEK2*1100delC heterozygotes compared with noncarriers, the age- and sex-adjusted hazard ratios were 5.76 (95% CI, 2.12 to 15.6) for stomach cancer, 3.61 (95% CI, 1.33 to 9.79) for kidney cancer, 3.45 (95% CI, 1.09 to 10.9) for sarcoma, and 1.60 (95% CI, 1.00 to 2.56) for prostate cancer. CONCLUSION: CHEK2*1100delC heterozygosity is associated with 15% to 82% increased risk for at least some cancers in addition to breast cancer. This information may be useful in clinical counseling of patients with this loss-of-function mutation. PMID- 26884564 TI - Brachytherapy: Where Has It Gone...Again? PMID- 26884566 TI - Reply to A.J. Olszewski et al. PMID- 26884565 TI - Identification of Patients Who Benefit From Bevacizumab in High-Grade Glioma-An Easy Question Turned Difficult: Treat the Scan or the Patient? PMID- 26884567 TI - Multiple Dimensions of Value: Evaluative Frameworks for New Cancer Therapies. PMID- 26884568 TI - Reply to M.C. Scholz et al. PMID- 26884569 TI - Cetuximab in Human Papillomavirus-Positive Oropharynx Carcinoma. PMID- 26884570 TI - Reply to M.C. Scholz et al. PMID- 26884571 TI - Targeting the Vascular Endothelial Growth Factor Pathway in Gastric Cancer: A Hit or a Miss? PMID- 26884572 TI - Using a Population-Based Analysis to Determine the Management and Treatment of Early-Stage Small-Cell Lung Cancer. PMID- 26884573 TI - Big Data, Small Effects. PMID- 26884574 TI - Survival Claims From Observational Data on Cancer Therapy. PMID- 26884575 TI - Reply to T.J. Kruser et al. PMID- 26884576 TI - Query About the Frequency of Biopsy Complications. PMID- 26884577 TI - Pointed Progress in Second-Line Advanced Non-Small-Cell Lung Cancer: The Rapidly Evolving Field of Checkpoint Inhibition. AB - PURPOSE: Non-small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second line advanced NSCLC. METHODS: Our systematic search revealed 20 clinical trials evaluating checkpoint inhibitors in the second-line setting, three of which were randomized trials comparing programmed cell death protein 1 and programmed death ligand 1 (PD-L1) inhibitors to docetaxel, the current standard of care in this setting. RESULTS: A randomized phase II trial comparing the PD-L1 inhibitor atezolizumab to docetaxel did not demonstrate improved survival for atezolizumab in patients overall, although a trend toward improved survival with increased PD L1 expression was apparent. Twin phase III trials showed significantly improved survival for the programmed cell death protein 1 inhibitor nivolumab compared with docetaxel in patients with both squamous and nonsquamous disease. PD-L1 expression correlated with improved survival in patients with nonsquamous disease, and patients with low levels of PD-L1 expression (< 10%) and those with EGFR mutations are unlikely to benefit. Checkpoint inhibitor therapy is generally well tolerated and associated with low rates of grade 3 or 4 adverse events compared with standard care. CONCLUSION: Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology. PMID- 26884578 TI - Burden of Geriatric Events Among Older Adults Undergoing Major Cancer Surgery. AB - PURPOSE: Most malignancies are diagnosed in older adults who are potentially susceptible to aging-related health conditions; however, the manifestation of geriatric syndromes during surgical cancer treatment is not well quantified. Accordingly, we sought to assess the prevalence and ramifications of geriatric events during major surgery for cancer. PATIENTS AND METHODS: Using Nationwide Inpatient Sample data from 2009 to 2011, we examined hospital admissions for major cancer surgery among elderly patients (ie, age >= 65 years) and a referent group age 55 to 64 years. From these observations, we identified geriatric events that included delirium, dehydration, falls and fractures, failure to thrive, and pressure ulcers. We then estimated the collective prevalence of these events according to age, comorbidity, and cancer site and further explored their relationship with other hospital-based outcomes. RESULTS: Within a weighted sample of 939,150 patients, we identified at least one event in 9.2% of patients. Geriatric events were most common among patients age >= 75 years, with a Charlson comorbidity score >= 2, and who were undergoing surgery for cancer of the bladder, ovary, colon and/or rectum, pancreas, or stomach (P < .001). Adjusting for patient and hospital characteristics, those patients who experienced a geriatric event had a greater likelihood of concurrent complications (odds ratio [OR], 3.73; 95% CI, 3.55 to 3.92), prolonged hospitalization (OR, 5.47; 95% CI, 5.16 to 5.80), incurring high cost (OR, 4.97; 95% CI, 4.58 to 5.39), inpatient mortality (OR, 3.22; 95% CI, 2.94 to 3.53), and a discharge disposition other than home (OR, 3.64; 95% CI, 3.46 to 3.84). CONCLUSION: Many older patients who receive cancer-directed surgery experience a geriatric event, particularly those who undergo major abdominal surgery. These events are linked to operative morbidity, prolonged hospitalization, and more expensive health care. As our population ages, efforts focused on addressing conditions and complications that are more common in older adults will be essential to delivering high-quality cancer care. PMID- 26884580 TI - Active Surveillance for the Management of Localized Prostate Cancer (Cancer Care Ontario Guideline): American Society of Clinical Oncology Clinical Practice Guideline Endorsement. AB - PURPOSE: To endorse Cancer Care Ontario's guideline on Active Surveillance for the Management of Localized Prostate Cancer. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines developed by other professional organizations. METHODS: The Active Surveillance for the Management of Localized Prostate Cancer guideline was reviewed for developmental rigor by methodologists. The ASCO Endorsement Panel then reviewed the content and the recommendations. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the Active Surveillance for the Management of Localized Prostate Cancer guideline, published in May 2015, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorsed the Active Surveillance for the Management of Localized Prostate Cancer guideline with added qualifying statements. The Cancer Care Ontario recommendation regarding 5-alpha reductase inhibitors was not endorsed by the ASCO panel. RECOMMENDATIONS: For most patients with low-risk (Gleason score <= 6) localized prostate cancer, active surveillance is the recommended disease management strategy. Factors including younger age, prostate cancer volume, patient preference, and ethnicity should be taken into account when making management decisions. Select patients with low-volume, intermediate-risk (Gleason 3 + 4 = 7) prostate cancer may be offered active surveillance. Active surveillance protocols should include prostate-specific antigen testing, digital rectal examinations, and serial prostate biopsies. Ancillary radiologic and genomic tests are investigational but may have a role in patients with discordant clinical and/or pathologic findings. Patients who are reclassified to a higher risk category (Gleason score >= 7) or who have significant increases in tumor volume on subsequent biopsies should be offered active therapy. PMID- 26884579 TI - Improved Method to Stratify Elderly Patients With Cancer at Risk for Competing Events. AB - PURPOSE: To compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events. METHODS: We identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (omega) using the Akaike Information Criterion. RESULTS: In each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8. CONCLUSION: Compared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality. PMID- 26884581 TI - Default Options: Opportunities to Improve Quality and Value in Oncology. PMID- 26884583 TI - Bispecific T-Cell Engagers (BiTEs) as Treatment of B-Cell Lymphoma. PMID- 26884582 TI - Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma: Final Results From a Phase I Study. AB - PURPOSE: Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome-negative acute B lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: This 3 + 3 design, phase I dose escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 MUg/m(2)/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate. RESULTS: Between 2004 and 2011, 76 heavily pretreated patients with relapsed/refractory NHL, who included 14 with diffuse large B-cell lymphoma, were enrolled; 42 received treatment in the formal dose-escalation phase. Neurologic events were dose limiting, and 60 MUg/m(2)/day was established as the MTD. Thirty four additional patients were recruited to evaluate antilymphoma activity and strategies for mitigating neurologic events at a prespecified MTD. Stepwise dosing (5 to 60 MUg/m(2)/day) plus pentosan polysulfate SP54 (n = 3) resulted in no treatment discontinuations; single-step (n = 5) and double-step (n = 24) dosing entailed two and seven treatment discontinuations due to neurologic events, respectively. Grade 3 neurologic events occurred in 22% of patients (no grade 4/5). Among patients treated at 60 MUg/m(2)/day (target dose; n = 35), the overall response rate was 69% across NHL subtypes and 55% for diffuse large B cell lymphoma (n = 11); median response duration was 404 days (95% CI, 207 to 1,129 days). CONCLUSION: In this phase I study of relapsed/refractory NHL, continuous infusion with CD19-targeted immunotherapy blinatumomab at various doses and schedules was feasible, with an MTD of 60 MUg/m(2)/day. Single-agent blinatumomab showed antilymphoma activity. PMID- 26884584 TI - Comparison of Treatment Effects Measured by the Hazard Ratio and by the Ratio of Restricted Mean Survival Times in Oncology Randomized Controlled Trials. AB - PURPOSE: We aimed to compare empirically the treatment effects measured by the hazard ratio (HR) and by the difference (and ratio) of restricted mean survival times (RMST) in oncology randomized trials. METHODS: We selected oncology randomized controlled trials from five leading journals during the last 6 months of 2014. We reconstructed individual patient data for one time-to-event outcome from each trial, preferably the primary outcome. We reanalyzed each trial and compared the treatment effect estimated by the HR with that by the difference (and ratio) of RMST. We estimated an average ratio of the HR to the ratio of RMST; an average ratio less than one indicates more optimistic assessments with HRs. RESULTS: We analyzed 54 randomized controlled trials totaling 33,212 patients. The selected outcome was overall survival in 21 (39%) trials. There was evidence of nonproportionality of hazards in 13 (24%) trials. The HR and RMST based measures were in agreement regarding the statistical significance of the effect, except in one case. The median HR was 0.84 (Q1 to Q3 range, 0.67 to 0.97) and the median difference in RMST was 1.12 months (range, 0.22 to 2.75 months). The average ratio of the HR to the ratio of RMST was 1.11 (95% CI, 1.07 to 1.15), with substantial between-trial variability (I(2) = 86%). Results were consistent by outcome type (overall survival v other outcomes) and whether the proportional hazard assumption held or not. CONCLUSION: On average, the HR provided significantly larger treatment effect estimates than the ratio of RMST. The HR may seem large when the absolute effect is small. RMST-based measures should be routinely reported in randomized trials with time-to-event outcomes. PMID- 26884586 TI - Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. AB - PURPOSE: To update the ASCO adjuvant endocrine therapy guideline based on emerging data concerning the benefits and risks of ovarian suppression in addition to standard adjuvant therapy in premenopausal women with estrogen receptor-positive breast cancer. METHODS: ASCO convened an Update Panel and conducted a systematic review of randomized clinical trials investigating ovarian suppression. RESULTS: Two trials investigating the addition of ovarian suppression to tamoxifen did not show an overall clinical benefit for ovarian suppression. Nonetheless, the addition of ovarian suppression to standard adjuvant therapy with tamoxifen or with an aromatase inhibitor improved disease free survival and improved freedom from breast cancer and distant recurrence compared with tamoxifen alone among the subset of patients who were at sufficient risk for recurrence such that adjuvant chemotherapy was warranted. Compared with tamoxifen alone, ovarian suppression was associated with a substantial increase in menopausal symptoms, sexual dysfunction, and diminished quality of life. RECOMMENDATIONS: The Panel recommends that higher-risk patients should receive ovarian suppression in addition to adjuvant endocrine therapy, whereas lower-risk patients should not. Women with stage II or III breast cancers who would ordinarily be advised to receive adjuvant chemotherapy should receive ovarian suppression with endocrine therapy. The panel recommends that some women with stage I or II breast cancers at higher risk of recurrence who might consider chemotherapy may also be offered ovarian suppression with endocrine therapy. Women with stage I breast cancers not warranting chemotherapy should not receive ovarian suppression, nor should women with node-negative cancers 1 cm or less. Ovarian suppression may be administered with either tamoxifen or an aromatase inhibitor. Additional information is available at www.asco.org/guidelines/endocrinebreast and www.asco.org/guidelineswiki. PMID- 26884585 TI - Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. AB - PURPOSE: There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). RESULTS: Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. CONCLUSION: These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. PMID- 26884587 TI - Neutralization of pro-inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis. AB - Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll-like receptor 2(TLR2) dimerization by a TLR2 transmembrane peptide (TLR2-p) ameliorated DSS-induced colitis by interfering specifically with the activation of Ly6C(+) monocytes without affecting their recruitment to the colon. We report that TLR2-p directly interacts with TLR2 within the membrane, leading to inhibition of TLR2-TLR6/1 assembly induced by natural ligands. This was associated with decreased levels of extracellular signal-regulated kinases (ERK) signaling and reduced secretion of pro inflammatory cytokines, such as interleukin (IL)-6, IL-23, IL-12, and IL-1beta. Altogether, our study provides insights into the essential role of TLR2 dimerization in the activation of pathogenic pro-inflammatory Ly6C(hi) monocytes and suggests that inhibition of this aggregation by TLR2-p might have therapeutic potential in the treatment of acute gut inflammation. PMID- 26884588 TI - Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer. AB - BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab +/- everolimus). Patients with >=50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678. PMID- 26884589 TI - Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan. AB - BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP. PMID- 26884590 TI - Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29). AB - BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh <=7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54 83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199. PMID- 26884593 TI - Another surprising role for exosomes? Improving next-generation sequencing-based cancer diagnostics in liquid biopsies. PMID- 26884591 TI - What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC). AB - BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a recently described pathologic entity. We report the case of a patient with an initial diagnosis of salivary acinic cell carcinoma later reclassified as MASC after next-generation sequencing revealed an ETV6-NTRK3 fusion. PATIENTS AND METHODS: This alteration was targeted with the pan-Trk inhibitor entrectinib (Ignyta), which possesses potent in vitro activity against cell lines containing various NTRK1/2/3 fusions. RESULTS: A dramatic and durable response was achieved with entrectinib in this patient, followed by acquired resistance that correlated with the appearance of a novel NTRK3 G623R mutation. Structural modeling predicts that this alteration sterically interferes with drug binding, correlating to decreased sensitivity to drug inhibition observed in cell-based assays. CONCLUSIONS: This first report of clinical activity with TrkC inhibition and the development of acquired resistance in an NTRK3-rearranged cancer emphasize the utility of comprehensive molecular profiling and targeted therapy for rare malignancies (NCT02097810). PMID- 26884594 TI - Cancer mortality in cohorts of workers in the European rubber manufacturing industry first employed since 1975. AB - BACKGROUND: Increased cancer risk has been reported among workers in the rubber manufacturing industry employed before the 1960s. It is unclear whether risk remains increased among workers hired subsequently. The present study focused on risk of cancer mortality for rubber workers first employed since 1975 in 64 factories. PATIENTS AND METHODS: Anonymized data from cohorts of rubber workers employed for at least 1 year from Germany, Italy, Poland, Sweden, and the UK were pooled. Standardized mortality ratios (SMRs), based on country-specific death rates, were reported for bladder and lung cancer (primary outcomes of interest), for other selected cancer sites, and for cancer sites with a minimum of 10 deaths in men or women. Analyses stratified by type of industry, period, and duration of employment were carried out. RESULTS: A total of 38 457 individuals (29 768 men; 8689 women) contributed to 949 370 person-years. No increased risk of bladder cancer was observed [SMR = 0.80, 95% confidence interval (CI) 0.46; 1.38]. The risk of lung cancer death was reduced (SMR = 0.81, 95% CI 0.70; 0.94). No statistically significant increased risk was observed for any other cause of death. A reduced risk was evident for total cancer mortality (SMR = 0.81, 95% CI 0.76; 0.87). Risks were lower for workers in the tyre industry compared with workers in the general rubber goods sector. Analysis by employment duration showed a negative trend with SMRs decreasing with increasing duration of employment. In an analysis of secondary end points, when stratified by type of industry and period of first employment, excess risks of myeloma and gastric cancer were observed each due, essentially, to results from one centre. CONCLUSION: No consistent increased risk of cancer death was observed among rubber workers first employed since 1975, no overall analysis of the pooled cohort produced significantly increased risk. Continued surveillance of the present cohorts is required to confirm the absence of long-term risk. PMID- 26884595 TI - Population-level trends in the distribution of body mass index in England, 1992 2013. AB - BACKGROUND: Changes over time of mean body weight or prevalence of overweight and obesity have been well documented. Less consideration has been given to describing the distribution to these changes particularly by socioeconomic status and sex. METHODS: We use data from the Health Survey for England for the years 1992-2013 to calculate the median, 5th and 95th centiles, and SD of body mass index (BMI). We tested differences using analysis of variance and quantile regression. Analyses were stratified by sex and level of education. RESULTS: There have been increases in the SD of BMI values over the period. While median BMI has increased, there has been a larger increase of the 95th centile. These trends were consistent by sex and level of education, although significant differences were observed in values. CONCLUSIONS: Our results demonstrate that changes in median BMI over time do not reflect changes in the distribution of BMI. Failing to understand the distribution of body weight in the population will hamper our projections of future patterns, as well as our ability to design effective public health strategies. PMID- 26884596 TI - Transmission Rates of 'Ca. Liberibacter asiaticus' by Asian Citrus Psyllid Are Enhanced by the Presence and Developmental Stage of Citrus Flush. AB - Asian citrus psyllid (Diaphorina citri Kuwayama) transmits a bacterium 'Candidatus Liberibacter asiaticus' (CLas) putatively responsible for a devastating citrus disease known as Asiatic huanglongbing (HLB) (citrus greening disease). The psyllid and disease have invaded many citrus-growing regions including the United States, where the disease is seriously jeopardizing the Florida citrus industry. We recently concluded research that showed CLas transmission rates are increased when citrus flush is present. Flush is any new leaf growth ranging in development from first emergence up until the leaves are fully expanded yet still tender. In an experiment with seedlings of a rootstock cultivar 'US-942', a 1-wk infestation of 20 Asian citrus psyllids from an infected colony resulted in 53-60% of seedlings becoming infected when flush was present compared with only 7% when no flush was present. In a second experiment with 'US-942', 77-97% of seedlings became infected when flush was present compared with 40% when no flush was present. A similar experiment with 'Valencia' sweet orange resulted in 23, 80, and 3% seedlings becoming infected when young, older, or no flush was present, respectively. Young plants are therefore more likely to contract HLB if flush is present, with older flush promoting higher infection rates under the conditions of this study. Based on this finding, healthy citrus should be protected from Asian citrus psyllid infestations throughout a flush. To evaluate germplasm for CLas resistance, inoculations using infected Asian citrus psyllid would best be achieved if flush is present. PMID- 26884597 TI - Focus Issue: Cell biology meets cancer therapy. AB - Cells are the targets of anticancer therapy, whether the therapy is directed at the tumor cells themselves or the cells of the immune system. Articles in this issue and in the 2015 Science Signaling archives provide insights into what makes a cell responsive to therapy and how understanding the cellular processes affected by the drugs (including endosomal trafficking and response to proteotoxic stress) can lead to personalized cancer therapies, thereby minimizing side effects and ineffective treatment strategies. PMID- 26884592 TI - Long-course oxaliplatin-based preoperative chemoradiation versus 5 * 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. AB - BACKGROUND: Improvements in local control are required when using preoperative chemoradiation for cT4 or advanced cT3 rectal cancer. There is therefore a need to explore more effective schedules. PATIENTS AND METHODS: Patients with fixed cT3 or cT4 cancer were randomized either to 5 * 5 Gy and three cycles of FOLFOX4 (group A) or to 50.4 Gy in 28 fractions combined with two 5-day cycles of bolus 5 Fu 325 mg/m(2)/day and leucovorin 20 mg/m(2)/day during the first and fifth week of irradiation along with five infusions of oxaliplatin 50 mg/m(2) once weekly (group B). The protocol was amended in 2012 to allow oxaliplatin to be then foregone in both groups. RESULTS: Of 541 entered patients, 515 were eligible for analysis; 261 in group A and 254 in group B. Preoperative treatment acute toxicity was lower in group A than group B, P = 0.006; any toxicity being, respectively, 75% versus 83%, grade III-IV 23% versus 21% and toxic deaths 1% versus 3%. R0 resection rates (primary end point) and pathological complete response rates in groups A and B were, respectively, 77% versus 71%, P = 0.07, and 16% versus 12%, P = 0.17. The median follow-up was 35 months. At 3 years, the rates of overall survival and disease-free survival in groups A and B were, respectively, 73% versus 65%, P = 0.046, and 53% versus 52%, P = 0.85, together with the cumulative incidence of local failure and distant metastases being, respectively, 22% versus 21%, P = 0.82, and 30% versus 27%, P = 0.26. Postoperative and late complications rates in group A and group B were, respectively, 29% versus 25%, P = 0.18, and 20% versus 22%, P = 0.54. CONCLUSIONS: No differences were observed in local efficacy between 5 * 5 Gy with consolidation chemotherapy and long-course chemoradiation. Nevertheless, an improved overall survival and lower acute toxicity favours the 5 * 5 Gy schedule with consolidation chemotherapy. CLINICAL TRIAL NUMBER: The trial is registered as ClinicalTrials.gov number NCT00833131. PMID- 26884598 TI - ONC201: Stressing tumors to death. AB - The small molecule ONC201 was identified in a screen for compounds that would induce expression of the gene encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in tumors and thus cause an autocrine- or paracrine induced death in tumor cells. Two Research Articles in this issue of Science Signaling by Ishizawa et al. and Kline et al. describe how ONC201 can also trigger cytotoxicity by inducing a stress response. The mechanisms of the stress response induced differ between hematological malignancies and solid tumors, highlighting the complexity of ONC201-induced toxicity and raising intriguing issues of tissue-specific pathways activated by the drug. PMID- 26884599 TI - ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies. AB - The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2alpha. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2alpha. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. PMID- 26884600 TI - ONC201 kills solid tumor cells by triggering an integrated stress response dependent on ATF4 activation by specific eIF2alpha kinases. AB - ONC201 (also called TIC10) is a small molecule that inactivates the cell proliferation- and cell survival-promoting kinases Akt and ERK and induces cell death through the proapoptotic protein TRAIL. ONC201 is currently in early-phase clinical testing for various malignancies. We found through gene expression and protein analyses that ONC201 triggered an increase in TRAIL abundance and cell death through an integrated stress response (ISR) involving the transcription factor ATF4, the transactivator CHOP, and the TRAIL receptor DR5. ATF4 was not activated in ONC201-resistant cancer cells, and in ONC201-sensitive cells, knockdown of ATF4 or CHOP partially abrogated ONC201-induced cytotoxicity and diminished the ONC201-stimulated increase in DR5 abundance. The activation of ATF4 in response to ONC201 required the kinases HRI and PKR, which phosphorylate and activate the translation initiation factor eIF2alpha. ONC201 rapidly triggered cell cycle arrest, which was associated with decreased abundance of cyclin D1, decreased activity of the kinase complex mTORC1, and dephosphorylation of the retinoblastoma (Rb) protein. The abundance of X-linked inhibitor of apoptosis protein (XIAP) negatively correlated with the extent of apoptosis in response to ONC201. These effects of ONC201 were independent of whether cancer cells had normal or mutant p53. Thus, ONC201 induces cell death through the coordinated induction of TRAIL by an ISR pathway. PMID- 26884601 TI - TGF-beta inhibits the activation and functions of NK cells by repressing the mTOR pathway. AB - Transforming growth factor-beta (TGF-beta) is a major immunosuppressive cytokine that maintains immune homeostasis and prevents autoimmunity through its antiproliferative and anti-inflammatory properties in various immune cell types. We provide genetic, pharmacologic, and biochemical evidence that a critical target of TGF-beta signaling in mouse and human natural killer (NK) cells is the serine and threonine kinase mTOR (mammalian target of rapamycin). Treatment of mouse or human NK cells with TGF-beta in vitro blocked interleukin-15 (IL-15) induced activation of mTOR. TGF-beta and the mTOR inhibitor rapamycin both reduced the metabolic activity and proliferation of NK cells and reduced the abundances of various NK cell receptors and the cytotoxic activity of NK cells. In vivo, constitutive TGF-beta signaling or depletion of mTOR arrested NK cell development, whereas deletion of the TGF-beta receptor subunit TGF-betaRII enhanced mTOR activity and the cytotoxic activity of the NK cells in response to IL-15. Suppression of TGF-beta signaling in NK cells did not affect either NK cell development or homeostasis; however, it enhanced the ability of NK cells to limit metastases in two different tumor models in mice. Together, these results suggest that the kinase mTOR is a crucial signaling integrator of pro- and anti inflammatory cytokines in NK cells. Moreover, we propose that boosting the metabolic activity of antitumor lymphocytes could be an effective strategy to promote immune-mediated tumor suppression. PMID- 26884602 TI - Functional diversification of the potato R2R3 MYB anthocyanin activators AN1, MYBA1, and MYB113 and their interaction with basic helix-loop-helix cofactors. AB - In potato (Solanum tuberosum L.), R2R3 MYBs are involved in the regulation of anthocyanin biosynthesis. We examined sequences of these MYBs in cultivated potatoes, which are more complex than diploid potato due to ploidy and heterozygosity. We found amino acid variants in the C-terminus of the MYB StAN1, termed R0, R1, and R3, due to the presence of a repeated 10-amino acid motif. These variant MYBs showed some expression in both white and pigmented tubers. We found several new alleles or gene family members of R2R3 MYBs,StMYBA1 and StMYB113, which were also expressed in white potato tubers. From functional analysis in tobacco, we showed that the presence of a C-terminal 10-amino acid motif is optimal for activating anthocyanin accumulation. Engineering a motif back into a MYB lacking this sequence enhanced its activating ability. Versions of StMYBA1 and StMYB113 can also activate anthocyanin accumulation in tobacco leaves, with the exception of StMYB113-3, which has a partial R2R3 domain. We isolated five family members of potato StbHLH1, and one StJAF13, to test their ability to interact with MYB variants. The results showed that two alleles of StbHLH1 from white skin and red skin are non-functional, while three other StbHLH1s have different co-regulating abilities, and need to be activated by StJAF13. Combined with expression analysis in potato tuber, results suggest that StbHLH1 and StJAF13a re key co-regulators of anthocyanin biosynthesis, while the transcripts of MYB variants StAN1,StMYBA1, and StMYB113 are well expressed, even in the absence of pigmentation. PMID- 26884603 TI - Cell wall-associated ROOT HAIR SPECIFIC 10, a proline-rich receptor-like kinase, is a negative modulator of Arabidopsis root hair growth. AB - Plant cell growth is restricted by the cell wall, and cell wall dynamics act as signals for the cytoplasmic and nuclear events of cell growth. Among various receptor kinases, ROOT HAIR SPECIFIC 10 (RHS10) belongs to a poorly known receptor kinase subfamily with a proline-rich extracellular domain. Here, we report that RHS10 defines the root hair length of Arabidopsis thaliana by negatively regulating hair growth. RHS10 modulates the duration of root hair growth rather than the growth rate. As poplar and rice RHS10 orthologs also showed a root hair-inhibitory function, this receptor kinase-mediated function appears to be conserved in angiosperms. RHS10 showed a strong association with the cell wall, most probably through its extracellular proline-rich domain (ECD). Deletion analysis of the ECD demonstrated that a minimal extracellular part, which includes a few proline residues, is required for RHS10-mediated root hair inhibition. RHS10 suppressed the accumulation of reactive oxygen species (ROS) in the root, which are necessary for root hair growth. A yeast two-hybrid screening identified an RNase (RNS2) as a putative downstream target of RHS10. Accordingly, RHS10 overexpression decreased and RHS10 loss increased RNA levels in the hair growing root region. Our results suggest that RHS10 mediates cell wall-associated signals to maintain proper root hair length, at least in part by regulating RNA catabolism and ROS accumulation. PMID- 26884607 TI - Do Genes Determine Our Health? Implications for Designing Lifestyle Interventions and Drug Trials. PMID- 26884605 TI - The MC1R and ASIP Coat Color Loci May Impact Behavior in the Horse. AB - Shared signaling pathways utilized by melanocytes and neurons result in pleiotropic traits of coat color and behavior in many mammalian species. For example, in humans polymorphisms at MC1R cause red hair, increased heat sensitivity, and lower pain tolerance. In deer mice, rats, and foxes, ASIP polymorphisms causing black coat color lead to more docile demeanors and reduced activity. Horse (Equus caballus) base coat color is primarily determined by polymorphisms at the Melanocortin-1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) loci, creating a black, bay, or chestnut coat. Our goal was to investigate correlations between genetic loci for coat color and temperament traits in the horse. We genotyped a total of 215 North American Tennessee Walking Horses for the 2 most common alleles at the MC1R (E/e) and ASIP (A/a) loci using previously published PCR and RFLP methods. The horses had a mean age of 10.5 years and comprised 83 geldings, 25 stallions, and 107 mares. To assess behavior, we adapted a previously published survey for handlers to score horses from 1 to 9 on 20 questions related to specific aspects of temperament. We utilized principle component analysis to combine the individual survey scores into 4 factors of variation in temperament phenotype. A factor component detailing self-reliance correlated with genotypes at the ASIP locus; black mares (aa) were more independent than bay mares (A_) (P = 0.0063). These findings illuminate a promising and novel animal model for future study of neuroendocrine mechanisms in complex behavioral phenotypes. PMID- 26884604 TI - Formation of beta-glucogallin, the precursor of ellagic acid in strawberry and raspberry. AB - Ellagic acid/ellagitannins are plant polyphenolic antioxidants that are synthesized from gallic acid and have been associated with a reduced risk of cancer and cardiovascular diseases. Here, we report the identification and characterization of five glycosyltransferases (GTs) from two genera of the Rosaceae family (Fragaria and Rubus; F. * ananassa FaGT2*, FaGT2, FaGT5, F. vesca FvGT2, and R. idaeus RiGT2) that catalyze the formation of 1-O-galloyl-beta-D glucopyranose (beta-glucogallin) the precursor of ellagitannin biosynthesis. The enzymes showed substrate promiscuity as they formed glucose esters of a variety of (hydroxyl)benzoic and (hydroxyl)cinnamic acids. Determination of kinetic values and site-directed mutagenesis revealed amino acids that affected substrate preference and catalytic activity. Green immature strawberry fruits were identified as the main source of gallic acid, beta-glucogallin, and ellagic acid in accordance with the highest GT2 gene expression levels. Injection of isotopically labeled gallic acid into green fruits of stable transgenic antisense FaGT2 strawberry plants clearly confirmed the in planta function. Our results indicate that GT2 enzymes might contribute to the production of ellagic acid/ellagitannins in strawberry and raspberry, and are useful to develop strawberry fruit with additional health benefits and for the biotechnological production of bioactive polyphenols. PMID- 26884608 TI - Unraveling De Novo Copy Number Variants in Congenital Heart Defects: The Bottom of the Iceberg Is Under Attack. PMID- 26884609 TI - Complexities of Genetic Testing in Familial Dilated Cardiomyopathy. PMID- 26884610 TI - Methods for measuring myeloperoxidase activity toward assessing inhibitor efficacy in living systems. AB - Myeloperoxidase aids in clearance of microbes by generation of peroxidase mediated oxidants that kill leukocyte-engulfed pathogens. In this review, we will examine 1) strategies for in vitro evaluation of myeloperoxidase function and its inhibition, 2) ways to monitor generation of certain oxidant species during inflammation, and 3) how these methods can be used to approximate the total polymorphonuclear neutrophil chemotaxis following insult. Several optical imaging probes are designed to target reactive oxygen and nitrogen species during polymorphonuclear neutrophil inflammatory burst following injury. Here, we review the following 1) the broad effect of myeloperoxidase on normal physiology, 2) the difference between myeloperoxidase and other peroxidases, 3) the current optical probes available for use as surrogates for direct measures of myeloperoxidase derived oxidants, and 4) the range of preclinical options for imaging myeloperoxidase accumulation at sites of inflammation in mice. We also stress the advantages and drawbacks of each of these methods, the pharmacokinetic considerations that may limit probe use to strictly cell cultures for some reactive oxygen and nitrogen species, rather than in vivo utility as indicators of myeloperoxidase function. Taken together, our review should shed light on the fundamental rational behind these techniques for measuring myeloperoxidase activity and polymorphonuclear neutrophil response after injury toward developing safe myeloperoxidase inhibitors as potential therapy for chronic obstructive pulmonary disease and rheumatoid arthritis. PMID- 26884611 TI - CCR2 signaling contributes to the differentiation of protective inflammatory dendritic cells in Leishmania braziliensis infection. AB - In vertebrate hosts, Leishmania braziliensis parasites infect mainly mononuclear phagocytic system cells, which when activated by T helper cell type 1 cytokines produce nitric oxide and kill the pathogens. Chemokine (C-C motif) receptor 2 is a chemokine receptor that binds primarily chemokine (C-C motif) ligand 2 and has an important role in the recruitment of monocytic phagocytes. Although it has been reported that Leishmania braziliensis infection induces CCR2 expression in the lesions, the role of CCR2 during Leishmania braziliensis infection remains unknown. Here, we showed that CCR2 has a role in mediating protection against Leishmania braziliensis infection in mice. The absence of CCR2 resulted in increased susceptibility to infection and was associated with low amounts of Ly6C(+) inflammatory dendritic cells in the lesions, which we found to be the major sources of tumor necrosis factor production and induced nitric oxide synthase expression in C57BL/6 mice lesions. Consequently, CCR2(-/-) mice showed decreased tumor necrosis factor production and induced nitric oxide synthase expression, resulting in impaired parasite elimination. We also demonstrated that CCR2 has a role in directly mediating the differentiation of monocytes into inflammatory dendritic cells at the infection sites, contributing to the accumulation of inflammatory dendritic cells in Leishmania braziliensis lesions and subsequent control of parasite replication. Therefore, these data provide new information on the role of chemokines during the immune response to infections and identify a potential target for therapeutic interventions in cutaneous leishmaniasis. PMID- 26884613 TI - Through Thick and Thin: What Are the Septal Thickness Limits for Alcohol Septal Ablation? PMID- 26884612 TI - Predictors of Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: An Echocardiography and Cardiovascular Magnetic Resonance Imaging Study. AB - BACKGROUND: Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required. METHODS AND RESULTS: One hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient >=50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased >=50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment (r=0.371; P<0.001), basal anteroseptal segment (r=0.527; P<0.001), and total thickness of the above 2 segments (r=0.672; P<0.001). The area under the receiver operating curves were 0.68, 0.79 and 0.89 for predictive analysis (all P<0.001). The cutoff thickness of the segment 1+2 was 50.9 mm, which yielded a sensitivity of 86% and specificity of 77%. CONCLUSIONS: Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA. PMID- 26884614 TI - Tetracyclines increase lipid phosphate phosphatase expression on plasma membranes and turnover of plasma lysophosphatidate. AB - Extracellular lysophosphatidate and sphingosine 1-phosphate (S1P) are important bioactive lipids, which signal through G-protein-coupled receptors to stimulate cell growth and survival. The lysophosphatidate and S1P signals are terminated partly by degradation through three broad-specificity lipid phosphate phosphatases (LPPs) on the cell surface. Significantly, the expression of LPP1 and LPP3 is decreased in many cancers, and this increases the impact of lysophosphatidate and S1P signaling. However, relatively little is known about the physiological or pharmacological regulation of the expression of the different LPPs. We now show that treating several malignant and nonmalignant cell lines with 1 MUg/ml tetracycline, doxycycline, or minocycline significantly increased the extracellular degradation of lysophosphatidate. S1P degradation was also increased in cells that expressed high LPP3 activity. These results depended on an increase in the stabilities of the three LPPs and increased expression on the plasma membrane. We tested the physiological significance of these results and showed that treating rats with doxycycline accelerated the clearance of lysophosphatidate, but not S1P, from the circulation. However, administering 100 mg/kg/day doxycycline to mice decreased plasma concentrations of lysophosphatidate and S1P. This study demonstrates a completely new property of tetracyclines in increasing the plasma membrane expression of the LPPs. PMID- 26884615 TI - Decade-Long Trends (2001-2011) in the Incidence and Hospital Death Rates Associated with the In-Hospital Development of Cardiogenic Shock after Acute Myocardial Infarction. AB - BACKGROUND: Limited information is available about relatively contemporary trends in the incidence and hospital case-fatality rates of cardiogenic shock in patients hospitalized with acute myocardial infarction. The purpose of this population-based study was to describe decade long trends (2001-2011) in the incidence and hospital case-fatality rates for patients who developed cardiogenic shock during hospitalization for an acute myocardial infarction. METHODS AND RESULTS: The study population consisted of 5686 residents of central Massachusetts hospitalized with acute myocardial infarction at all 11 medical centers in the Worcester, MA, metropolitan area during 6 biennial periods between 2001 and 2011, who did not have cardiogenic shock at the time of hospital presentation. On average, 3.7% of these patients developed cardiogenic shock during their acute hospitalization with nonsignificant and inconsistent trends noted over time in both crude (3.7% in 2001/2003; 4.5% in 2005/2007; 2.7% in 2009/2011; P=0.19) and multivariable adjusted analyses. The overall in-hospital case-fatality rate for patients who developed cardiogenic shock was 41.4%. The crude and multivariable adjusted odds of dying after cardiogenic shock declined during the most recent study years (47.1% dying in 2001/2003, 42.0% dying in 2005/2007, and 28.6% dying in 2009/2011). Increases in the use of evidence-based cardiac medications, and interventional procedures paralleled the increasing hospital survival trends. CONCLUSIONS: We found suggestions of a decline in the death, but not incidence, rates of cardiogenic shock over time. These encouraging trends in hospital survival are likely because of advances in the early recognition and aggressive management of patients who develop cardiogenic shock. PMID- 26884617 TI - Morphological and chemical analysis of bainite in Cu-17Al-11Mn (at.%) alloys by using orthogonal FIB-SEM and double-EDS STEM. AB - In this study, new microscopy techniques were developed for understanding the mechanism for the bainitic transformation in a Cu-17Al-11Mn (at%) alloy. An orthogonally arranged focused ion beam and a scanning electron microscope were employed to observe three-dimensional (3D) morphology of the bainite phase, in addition to compositional analysis by using a scanning transmission electron microscope equipped with a double-detector energy-dispersive X-ray spectrometer system. The 3D morphology of these samples was observed at different aging times and aging temperatures; the results obtained indicated that with increasing aging time and/or aging temperature, the bainite phase at the initial stage of formation exhibits a plate-like shape, which changes to a lenticular form. A habit plane was uniquely determined as ~{9 3 2} by the combination of 3D image reconstruction and an electron back-scattered diffraction technique. The compositional analysis revealed the spatial distribution of the compositional variation between the bainite and matrix phases in the initial stages of the transformation. In the bainite phase, the Cu concentration was higher, while the concentrations of Al and Mn were lower than those in the surrounding matrix, indicative of the diffusion of the constituent elements with the growth of the bainite phase. PMID- 26884618 TI - Higher-order assemblies of BAR domain proteins for shaping membranes. AB - Most cellular organelles contain lipid bilayer membranes. The earliest characterization of cellular organelles was performed by electron microscopy observation of such membranes. However, the precise mechanisms for shaping the membrane in particular subcellular organelles is poorly understood. Classically, the overall cellular shape, i.e. the shape of the plasma membrane, was thought to be governed by the reorganization of cytoskeletal components such as actin and microtubules. The plasma membrane contains various submicron structures such as clathrin-coated pits, caveolae, filopodia and lamellipodia. These subcellular structures are either invaginations or protrusions and are associated with the cytoskeleton. Therefore, it could be hypothesized that there are membrane-binding proteins that cooperates with cytoskeleton in shaping of plasma membrane organelles. Proteins with the Bin-Amphiphysin-Rvs (BAR) domain connect a variety of membrane shapes to actin filaments. The BAR domains themselves bend the membranes by their rigidity and then mold the membranes into tubules through their assembly as spiral polymers, which are thought to be involved in the various submicron structures. Membrane tubulation by polymeric assembly of the BAR domains is supposed to be regulated by binding proteins, binding lipids and the mechanical properties of the membrane. This review gives an overview of BAR protein assembly, describes the significance of the assembly and discusses how to study the assembly in the context of membrane and cellular morphology. The technical problems encountered in microscopic observation of BAR domain assembly are also discussed. PMID- 26884616 TI - Prognostic Value of Lymphocyte G Protein-Coupled Receptor Kinase-2 Protein Levels in Patients With Heart Failure. AB - RATIONALE: Sympathetic nervous system hyperactivity is associated with poor prognosis in patients with heart failure (HF), yet routine assessment of sympathetic nervous system activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase-2 (GRK2) is upregulated in HF patients, causing dysfunctional beta-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. OBJECTIVE: The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated; thus, the purpose of this study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. METHODS AND RESULTS: We prospectively studied 257 HF patients with mean left ventricular ejection fraction of 31.4+/-8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP, and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental, and laboratory data. Over a mean follow-up period of 37.5+/-20.2 months (range, 3-60 months), there were 102 CV deaths. Age, left ventricular ejection fraction, New York Heart Association class, chronic obstructive pulmonary disease, chronic kidney disease, N-terminal-pro brain natriuretic peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all cause mortality. CONCLUSIONS: Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. PMID- 26884619 TI - Resuscitation outcomes of reproductive-age females who experienced out-of hospital cardiac arrest. AB - BACKGROUND: Although some studies have shown that women in their reproductive years have better resuscitation outcomes of out-of-hospital cardiac arrest (OHCA), conflicting results and methodological problems have also been noted. Thus, we evaluated the resuscitation outcomes of OHCA of females by age. METHODS: This was a prospective observational study using registry data from all OHCA cases between 2005 and 2012 in Japan. The subjects were females aged 18-110 years who suffered an out-of-hospital cardiac arrest. Logistic regression analyses were performed using total and propensity-matched patients. RESULTS: There were 381,123 OHCA cases that met the inclusion criteria. Among propensity-matched patients, females aged 18-49 and 50-60 years of age had similar rates of return of spontaneous circulation before hospital arrival and 1-month survival (all p>0.60). In contrast, females aged 18-49 years of age had significantly lower rates of 1-month survival with minimal neurological impairment than did females aged 50-60 years of age (after adjusting for selected variables: Cerebral Performance Category scale 1 or 2 (CPC (1, 2)), OR=0.45, p=0.020; Overall Performance Category scale 1 or 2 (OPC (1, 2)): OR=0.42, p= 0.014; after adjustment for all variables: CPC (1, 2), OR=0.27, p= 0.008; OPC (1, 2), OR=0.29, p=0.009). CONCLUSION: Women of reproductive age did not show improved resuscitation outcomes in OHCA. Additionally, women in their reproductive years showed worse neurological outcomes one month after the event, which may be explained by the negative effects of estrogen. These findings need to be verified in further studies. PMID- 26884620 TI - Intravenous nicorandil for treatment of the urgent phase acute heart failure syndromes: A randomized, controlled trial. AB - BACKGROUND: Vasodilators, such as nitroglycerin, have long been first-line treatments for acute heart failure syndromes (AHFS). Nicorandil is a vasodilator with dual potassium channel opening and nitrate properties. However, there are no randomized controlled studies of intravenous nicorandil safety and efficacy in the urgent phase AHFS. We examined the symptomatic, hemodynamic, and echocardiographic effects and safety, and 60-day clinical outcomes of intravenous nicorandil, in addition to standard therapy, in patients with AHFS in the urgent phase. METHODS: In this prospective, randomized controlled trial, 106 AHFS patients were randomized within one hour of arrival to receive either standard therapy (control group, n=56) or standard therapy plus simultaneous intravenous nicorandil (0.2 mg/kg bolus followed by 0.2 mg/kg/h for 24 h; nicorandil group, n=50). Outcomes were assessed at 60 days. RESULTS: Patients in the nicorandil group exhibited greater improvement of dyspnea as measured by change in a five point Likert scale compared to those in the control group (after 1 h infusion: p=0.006, 6 h; p<0.001). The nicorandil group also showed significantly improved E/e', an estimate of left ventricular filling pressure, at 1 and 24 h ( p=0.001 and p=0.004, respectively). In addition, intravenous nicorandil therapy was safe and did not cause side effects such as excessive hypotension or reflex tachycardia. However, it did not reduce all-cause mortality and readmission rates at 60 days. CONCLUSIONS: Addition of intravenous nicorandil to standard therapy for urgent phase AHFS improved dyspnea and left ventricular diastolic function but not 60-day outcome. PMID- 26884621 TI - Legal and Policy Interventions to Improve Patient Safety. PMID- 26884622 TI - Management of a Patient With Electrical Storm: Role of Epicardial Catheter Ablation. PMID- 26884624 TI - Rapid Reversal of Focal Left Ventricular Hypertrophy and Systolic Dysfunction Resulting From Myocardial Infiltration by Acute Lymphoblastic Leukemia. PMID- 26884625 TI - Aortic Dissection With Severe Aortic Regurgitation. PMID- 26884626 TI - Letter by Durmaz et al Regarding Article, "Trauma Exposure and Posttraumatic Stress Disorder Symptoms Predict Onset of Cardiovascular Events in Women". PMID- 26884628 TI - Letter by Murakami et al Regarding Article, "Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders: Relationships With Age, Aortic Size, Rate of Dilation, and Surgical Root Replacement". PMID- 26884627 TI - Response to Letter Regarding Article, "Trauma Exposure and Posttraumatic Stress Disorder Symptoms Predict Onset of Cardiovascular Events in Women". PMID- 26884629 TI - Letter by Weismann and Hager Regarding Article, "Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders: Relationships With Age, Aortic Size, Rate of Dilation, and Surgical Root Replacement". PMID- 26884630 TI - Response to Letters Regarding Article "Segmental Aortic Stiffness in Children and Young Adults With Connective Tissue Disorders: Relationships With Age, Aortic Size, Rate of Dilation, and Surgical Root Replacement". PMID- 26884631 TI - Letter by Garg et al Regarding Article, "Percutaneous Coronary Intervention at Centers With and Without On-Site Surgical Backup: An Updated Meta-Analysis of 23 Studies". PMID- 26884633 TI - 'Classic papers' in this issue of Acta Radiologica. PMID- 26884632 TI - Response to Letter Regarding Article, "Percutaneous Coronary Intervention at Centers With and Without On-Site Surgical Backup: An Updated Meta-Analysis of 23 Studies". PMID- 26884634 TI - A Case of Fracture of the Cranium with Accumulation of Air in the Cranial Cavity 1921. PMID- 26884635 TI - A Plateholder for Precise Roentgenography in Connection with Fluoroscopy 1921. PMID- 26884636 TI - Diffusion-weighted imaging in hemorrhagic ovarian cysts. PMID- 26884637 TI - Skimming the surface of underwater landslides. PMID- 26884640 TI - Lead and Arsenic Uptake by Leafy Vegetables Grown on Contaminated Soils: Effects of Mineral and Organic Amendments. AB - To assess strategies for mitigating Pb and As transfer into leafy vegetables from contaminated garden soils, we conducted greenhouse experiments using two field contaminated soils amended with materials expected to reduce metal phytoavailability. Lettuce and mustard greens grown on these soils were analysed by ICP-MS, showing that some Pb and As transfer into the vegetables occurred from both soils tested, but plant Pb concentrations were highly variable among treatment replicates. Soil-to-plant transfer was more efficient for As than for Pb. Contamination of the leaves by soil particles probably accounted for most of the vegetable Pb, since plant Pb concentrations were correlated to plant tissue concentrations of the immobile soil elements Al and Fe. This correlation was not observed for vegetable As concentrations, evidence that most of the soil-to-plant transfer for this toxic metal occurred by root uptake and translocation into the above-ground tissues. A follow-up greenhouse experiment with lettuce on one of the two contaminated soils revealed a lower and less variable foliar Pb concentration than observed in the first experiment, with evidence of less soil particle contamination of the crop. This reduced transfer of Pb to the crop appeared to be a physical effect attributable to the greater biomass causing reduced overall exposure of the above-ground tissues to the soil surface. Attempts to reduce soil Pb and As solubility and plant uptake by amendment at practical rates with stabilizing materials including composts, peat, Ca phosphate, gypsum and Fe oxide, were generally unsuccessful. Only Fe oxide reduced soluble As in the soil, but this effect did not persist. Phosphate amendment rapidly increased soil As solubility but had no measurable effect on either soil Pb solubility or concentrations of Pb or As in the leafy vegetables. The ineffectiveness of these amendments in reducing Pb transfer into leafy vegetables is attributed in this study to the low initial Pb solubility of the studied soils and the fact that the primary mechanism of Pb transfer is physical contamination. PMID- 26884641 TI - In Vitro Evaluation of a Device for Intra-Pulmonary Aerosol Generation and Delivery. AB - For infants born with respiratory distress syndrome (RDS), liquid bolus delivery of surfactant administered through an endotracheal tube is common practice. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. Aerosolized surfactant therapy has been explored as an alternative. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation. A novel aerosol generator (MicrojetTM) is evaluated herein for intrapulmonary aerosol generation within an endotracheal tube and tested with Curosurf and Infasurf surfactants. Compared with other aerosol delivery devices, this process utilizes low air flow (range 0.01-0.2 L/min) that is ideal for limiting potential barotrauma to the premature newborn lung. The mass mean diameter (MMD) of the particles for both tested surfactants was less than 4 MUm, which is ideal for both uniform and distal lung delivery. As an indicator of phospholipid function, surfactant surface tension was measured before and after aerosol formation; with no significant difference. Moreover, this device has an outside diameter of <1mm, which permits insertion into an endotracheal tube (of even 2.0 mm). In the premature infant where intravenous access is either technically challenging or difficult, aerosol drug delivery may provide an alternative route in patient resuscitation, stabilization and care. Other potential applications of this type of device include the delivery of nutrients, antibiotics, and analgesics via the pulmonary route. PMID- 26884642 TI - The Role of Eugenol in the Prevention of Acute Pancreatitis-Induced Acute Kidney Injury: Experimental Study. AB - Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15-20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220-350 g were divided into 3 groups: (1) Sham, with sham surgery; (2) Control, with induction of acute pancreatitis, through ligation of the biliopancreatic duct; and (3) Eugenol, with induction of acute pancreatitis and eugenol administration at a dose of 15 mg/kg. Serum urea and creatinine, histopathological changes, TNF-alpha, IL-6, and MPO activity in the kidneys were evaluated at predetermined time intervals. Results. The group that was administered eugenol showed milder histopathological changes than the Control group, TNF-alpha activity was milder in the Eugenol group, and there was no difference in activity for MPO and IL-6. Serum urea and creatinine levels were lower in the Eugenol group than in the Control group. Conclusions. Eugenol administration was protective for the kidneys in an experimental model of acute pancreatitis in rats. PMID- 26884639 TI - Emerging trends in nutraceutical applications of whey protein and its derivatives. AB - The looming food insecurity demands the utilization of nutrient-rich residues from food industries as value-added products. Whey, a dairy industry waste has been characterized to be excellent nourishment with an array of bioactive components. Whey protein comprises 20 % of total milk protein and it is rich in branched and essential amino acids, functional peptides, antioxidants and immunoglobulins. It confers benefits against a wide range of metabolic diseases such as cardiovascular complications, hypertension, obesity, diabetes, cancer and phenylketonuria. The protein has been validated to boost recovery from resistance exercise-injuries, stimulate gut physiology and protect skin against detrimental radiations. Apart from health invigoration, whey protein has proved its suitability as fat replacer and emulsifier. Further, its edible and antimicrobial packaging potential renders its highly desirable in food as well as pharmaceutical sectors. Considering the enormous nutraceutical worth of whey protein, this review emphasizes on its established and emerging biological roles. Present and future scopes in food processing and dietary supplement formulation are discussed. Associated hurdles are identified and how technical advancement might augment its applications are explored. This review is expected to provide valuable insight on whey protein-fortified functional foods, associated technical hurdles and scopes of improvement. PMID- 26884643 TI - Sphingosine-1-Phosphate/Sphingosine-1-Phosphate Receptor 2 Axis Can Promote Mouse and Human Primary Mast Cell Angiogenic Potential through Upregulation of Vascular Endothelial Growth Factor-A and Matrix Metalloproteinase-2. AB - Mast cells (MC) are present in most vascularized tissues around the vasculature likely exerting immunomodulatory functions. Endowed with diverse mediators, resident MC represent first-line fine-tuners of local microenvironment. Sphingosine-1-phosphate (S1P) functions as a pluripotent signaling sphingolipid metabolite in health and disease. S1P formation occurs at low levels in resting MC and is upregulated upon activation. Its export can result in type 2 S1P receptor- (S1PR2-) mediated stimulation of MC, further fueling inflammation. However, the role of S1PR2 ligation in proangiogenic vascular endothelial growth factor- (VEGF-) A and matrix metalloproteinase- (MMP-) 2 release from MC is unknown. Using a preclinical MC-dependent model of acute allergic responses and in vitro stimulated primary mouse bone marrow-derived MC (BMMC) or human primary skin MC, we report that S1P signaling resulted in substantial amount of VEGF-A release. Similar experiments using S1pr2-deficient mice or BMMC or selective S1P receptor agonists or antagonists demonstrated that S1P/S1PR2 ligation on MC is important for VEGF-A secretion. Further, we show that S1P stimulation triggered transcriptional upregulation of VEGF-A and MMP-2 mRNA in human but not in mouse MC. S1P exposure also triggered MMP-2 secretion from human MC. These studies identify a novel proangiogenic axis encompassing MC/S1P/S1PR2 likely relevant to inflammation. PMID- 26884644 TI - Blood Genome-Wide Transcriptional Profiles of HER2 Negative Breast Cancers Patients. AB - Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2- breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of "chemokine signaling," "IL 8 signaling," and "communication between innate and adaptive immune cells" pathways in the blood of TNBC patients correlated with an increased inflammation and necrosis in their primary tumors. Overall, our data indicate that the presence of triple-negative breast cancer is associated with an enrichment of altered systemic immune-related pathways, suggesting that immunotherapy could possibly be synergistic to the chemotherapy, to improve the clinical outcome of these patients. PMID- 26884645 TI - Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential Counter-Regulatory Effect in Primary Sjogren's Syndrome. AB - Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjogren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease. PMID- 26884647 TI - Cannabinoid CB2 Receptor Mediates Nicotine-Induced Anti-Inflammation in N9 Microglial Cells Exposed to beta Amyloid via Protein Kinase C. AB - BACKGROUND: Reducing beta amyloid- (Abeta-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Abeta-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Abeta-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process. METHODS: We used Abeta1-42 to activate N9 microglial cells and observed nicotine-induced effects on microglial M1 and M2 biomarkers by using western blot, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that nicotine reduced the levels of M1 state markers, including inducible nitric oxide synthase (iNOS) expression and tumor necrosis factor alpha (TNF alpha) and interleukin- (IL-) 6 releases; meanwhile, it increased the levels of M2 state markers, including arginase-1 (Arg-1) expression and brain-derived neurotrophic factor (BDNF) release, in the Abeta-stimulated microglia. Coadministration of cannabinoid CB2 receptor antagonist or protein kinase C (PKC) inhibitor partially abolished the nicotine-induced effects. CONCLUSION: These findings indicated that cannabinoid CB2 receptor mediates nicotine-induced anti inflammation in microglia exposed to Abeta via PKC. PMID- 26884646 TI - Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer. AB - Macrophages are critical mediators of inflammation and important regulators of developmental processes. As a key phagocytic cell type, macrophages evolved as part of the innate immune system to engulf and process cell debris and pathogens. Macrophages produce factors that act directly on their microenvironment and also bridge innate immune responses to the adaptive immune system. Resident macrophages are important for acting as sensors for tissue damage and maintaining tissue homeostasis. It is now well-established that macrophages are an integral component of the breast tumor microenvironment, where they contribute to tumor growth and progression, likely through many of the mechanisms that are utilized during normal wound healing responses. Because macrophages contribute to normal mammary gland development and breast cancer growth and progression, this review will discuss both resident mammary gland macrophages and tumor-associated macrophages with an emphasis on describing how macrophages interact with their surrounding environment during normal development and in the context of cancer. PMID- 26884649 TI - Manipulation of P2X Receptor Activities by Light Stimulation. AB - P2X receptors are involved in amplification of inflammatory responses in peripheral nociceptive fibers and in mediating pain-related signals to the CNS. Control of P2X activation has significant importance in managing unwanted hypersensitive neuron responses. To overcome the limitations of chemical ligand treatment, optical stimulation methods of optogenetics and photoswitching achieve efficient control of P2X activation while allowing specificity at the target site and convenient stimulation by light illumination. There are many potential applications for photosensitive elements, such as improved uncaging methods, photoisomerizable ligands, photoswitches, and gold nanoparticles. Each technique has both advantages and downsides, and techniques are selected according to the purpose of the application. Technical advances not only provide novel approaches to manage inflammation or pain mediated by P2X receptors but also suggest a similar approach for controlling other ion channels. PMID- 26884651 TI - Clinical Signs in Surgery: Are They Still Relevant? PMID- 26884648 TI - Therapeutic Strategies for Neuropathic Pain: Potential Application of Pharmacosynthetics and Optogenetics. AB - Chronic pain originating from neuronal damage remains an incurable symptom debilitating patients. Proposed molecular modalities in neuropathic pain include ion channel expressions, immune reactions, and inflammatory substrate diffusions. Recent advances in RNA sequence analysis have discovered specific ion channel expressions in nociceptors such as transient receptor potential (TRP) channels, voltage-gated potassium, and sodium channels. G protein-coupled receptors (GPCRs) also play an important role in triggering surrounding immune cells. The multiple protein expressions complicate therapeutic development for neuropathic pain. Recent progress in optogenetics and pharmacogenetics may herald the development of novel therapeutics for the incurable pain. Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) facilitate the artificial manipulation of intracellular signaling through excitatory or inhibitory G protein subunits activated by biologically inert synthetic ligands. Expression of excitatory channelrhodopsins and inhibitory halorhodopsins on injured neurons or surrounding cells can attenuate neuropathic pain precisely controlled by light stimulation. To achieve the discrete treatment of injured neurons, we can exploit the transcriptome database obtained by RNA sequence analysis in specific neuropathies. This can recommend the suitable promoter information to target the injury sites circumventing intact neurons. Therefore, novel strategies benefiting from pharmacogenetics, optogenetics, and RNA sequencing might be promising for neuropathic pain treatment in future. PMID- 26884652 TI - Minimally Invasive Anal Fistula Treatment-a True Minimal Invasive Surgical Procedure. PMID- 26884650 TI - ET-1 Promotes Differentiation of Periodontal Ligament Stem Cells into Osteoblasts through ETR, MAPK, and Wnt/beta-Catenin Signaling Pathways under Inflammatory Microenvironment. AB - Periodontitis is a kind of chronic inflammatory disease that affects the tooth supporting tissues. ET-1 is related to periodontitis and involved in the regulation of cytokines, but the mechanisms remain unclear. The aim of this study is to investigate how ET-1 affects proinflammatory cytokine expression and differentiation in human periodontal ligament stem cells (PDLSCs). PDLSCs were isolated from the periodontal ligament tissues of periodontitis patients and then treated with ET-1 (1, 10, or 100 nM) for 12 h, 24 h, or 72 h. The osteogenic potential of PDLSCs was tested using ALP staining. TNF-alpha, IL-1beta, and IL-6 levels were evaluated by ELISA and western blot. Runx2, OCN, and COL1 mRNA and western levels were detected by RT-PCR and western blot, respectively. To examine the signaling pathways and molecular mechanisms involved in ET-1-mediated cytokine expression and osteogenic differentiation, ETR pathway, MAPKs pathway, Wnt/beta-catenin pathway, and Wnt/Ca(2+) pathway were detected by RT-PCR and western blot, respectively. ET-1 promoted differentiation of PDLSCs into osteoblasts by increasing secretion of TNF-alpha, IL-1beta, and IL-6 in a dose- and time-dependent manner. ET-1 also increased expression of Runx2, OCN, and COL1. ET-1 promotes differentiation of PDLSCs into osteoblasts through ETR, MAPK, and Wnt/beta-catenin signaling pathways under inflammatory microenvironment. PMID- 26884653 TI - Influence of Heparanase and VEGF-C mRNA Expressions in Lung Cancer. AB - The objective of this study is to investigate relationship between the expressions of heparanase and vascular endothelial growth factor-C (VEGF-C) mRNA and tumorigenesis, progression in human lung cancer. The expressions of heparanase and VEGF-C mRNA in 65 cases of lung cancer (31 cases of squamous cell carcinoma, 25 adenocarcinoma, 3 large cell carcinoma, and 6 small cell carcinoma), adjacent tissues of cancer, and normal tissues were tested by reverse transcription-polymerase chain reaction (RT-PCR) and analyzed by clinico pathological characteristics and prognosis of lung cancer. The rate of expressions of heparanase and VEGF-C mRNA in tumor tissues (55.4, 61.5 %) was significantly higher than that in adjacent tissues of cancer (12.3, 15.4 %) and normal tissues (3.1, 4.6 %) (P < 0.05). It was shown that heparanase and VEGF-C mRNA expressions did not correlate with the pathological type and grade of the tumor (P > 0.05), but they correlated with the clinical stage and survival time of the patients (P < 0.05). Overexpression of heparanase and VEGF-C mRNA in lung cancer tissues perhaps participates in regulation of tumorigenesis and progression. The expressions of heparanase and VEGF-C mRNA should be used as a useful marker of the biological behavior of lung cancer and as an independent prognosis factor for the patient's survival. PMID- 26884654 TI - The Post-Surgical Long-Term Behaviour of Lung Carcinoid Tumours. AB - Here, we report a retrospective evaluation of long-term behaviour of lung carcinoids after surgery. A total of 23 patients (17 with typical pulmonary carcinoids and 6 with atypical pulmonary carcinoids) were enrolled in our hospital from April 1994 to July 2009. All patients underwent intervention at the Unit of Surgery and then were followed at the Unit of Oncology. The standard protocol for patient monitoring consisted of follow-up at 3 months after surgery, 6 months after first control and annually for 5 years. The follow-up evaluations consisted in blood tests, imaging of chest and abdomen, bone scintigraphy, and brain computed tomography. In case of disease recurrence, patients underwent chemotherapy (etoposide, carboplatin) and radiotherapy. All patients were followed for a mean of follow-up period of 100 months, ranging between 20 and 203 months. In the group of typical carcinoid, the observed recurrence rate at 5 years was zero, at 10 years was 5.8 %, whereas the observed mortality rate at 5 and 10 years was zero. In the group of atypical carcinoid, both the recurrence rate and the mortality rate at 5 and 10 years were 16.6 %. A statistical significant difference (p = 0.002) in the recurrence rate between stage I and stage II was observed. The overall prognosis of pulmonary carcinoids was favourable, and the typical carcinoids presented a better prognosis than the atypical ones. The stage at time of diagnosis could be considered as a predictive prognostic factor. PMID- 26884655 TI - An Analysis of the Origins, Subjects, and Awards Received for Presentations at the Annual IASG Conferences (2009-2013). AB - s presented at scientific meetings are important for making ongoing research more widely known and may also reflect the quality of the parent institution's standard of patient care. We analyzed the abstracts presented at the annual meetings of IASG for the past 5 years for (i) medium of presentation (oral/poster/videos), (ii) subjects discussed, (iii) institution of origin, (iv) whether a prospective/ retrospective study or a case report, (v) changing trends, and (vi) awards received. Of the 1340 abstracts analyzed, there were 18.5 % oral, 74.9 % posters, and 6.5 % videos presented from 205 in 2009 to 388 in 2012. The main organs discussed were the liver (19.3 %) pancreas (18.8 %), and biliary system (14.4 %). Sixty percent was from the private sector with Sir Ganga Ram, SGRH (95) and the Apollo Hospital, New Delhi (60), being the most prolific. From public institutes, the abstracts were predominantly from PGIMER, Chandigarh (39) and GB Pant Hospital (37). Thirty-three percent was from DNB and 25 % from M.Ch GI Surgery centres and 42 % was from others (most of these were as posters). There were 1016 (75.8 %) prospective/retrospective studies and 324 (24.2 %) case reports. Presentations, especially those related to liver transplantation, showed an increase. The main awards were won by SGRH (8); AIIMS, New Delhi (7); and JIPMER, Puducherry (6). Over the last 5 years, abstracts presented at the IASG have increased in number especially those dealing with the hepato-pancreatico biliary system and liver transplantation. Most presentations were from "academic" departments, and similar analyses may inform us where we are heading and stimulate healthy competition. PMID- 26884656 TI - The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection. AB - Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student's t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 +/- 7.9 months and overall survival was 31.5 +/- 7.4 months in H. pylori-positive patients compared with 28.3 +/- 3.7 and 33.2 +/- 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes. PMID- 26884657 TI - Role of Combined Sentinel Lymph Node Biopsy and Axillary Node Sampling in Clinically Node-Negative Breast Cancer. AB - Axillary lymph node status is a prognostic marker in breast cancer management, and axillary surgery plays an important role in staging and local control. This study aims to assess whether a combination of sentinel lymph node biopsy (SLNB) using patent blue dye and axillary node sampling (ANS) offers equivalent identification rate to dual tracer technique. Furthermore, we aim to investigate whether there are any potential benefits to this combined technique. Retrospective study of 230 clinically node-negative patients undergoing breast conserving surgery for single T1-T3 tumours between 2006 and 2011. Axillae were staged using a combined blue dye SLNB/ANS technique. SLNs were localized in 226/230 (identification rate 98.3 %). Three of one hundred ninety-two patients with a negative SLN were found to have positive ANS nodes and 1/4 failed SLNB patients had positive ANS nodes. Thirty-four of two hundred twenty-six patients had SLN metastases and 11/34 (32.4 %) also had a positive non-sentinel lymph node on ANS. Twenty-one of twenty-four (87.5 %) node-positive T1 tumours had single node involvement. Nine of thirty-eight node-positive patients progressed to completion axillary clearance (cALND), and the rest were treated with axillary radiotherapy. Axillary recurrence was nil at median 5 year follow-up. Complementing SLNB with axillary node sampling (ANS) decreases the unavoidable false-negative rate associated with SLNB. Appropriate operator experience and technique can result in an SLN localization rate of 98 %, rivalling a dual tracer technique. The additional insight offered by ANS into the status of non-sentinel nodes has potential applications in an era of less frequent cALND. PMID- 26884658 TI - Effect of Curcumin in Experimental Peritonitis. AB - Despite medical advancements, the inflammatory cascade and oxidative stress worsen the prognosis in most cases of peritonitis. Curcumin has emerged as a potential antioxidant and anti-inflammatory agent in few of the acute inflammatory and infective conditions. We examined the effect of intraperitoneal injection of curcumin in endotoxin-induced peritonitis in rats. The blood and peritoneal fluid samples were collected at 3 and 24 h following the induction of peritonitis. Animals were sacrificed at 24 h and the organs preserved. The histopathological report of lung, liver, and intestines in the curcumin-treated rats showed maintenance of tissue architecture to a large extent compared to the control group which showed massive congestion, hemorrhage, and necrosis. The blood and peritoneal fluid total count and differential neutrophil counts were significantly higher at 24 h of induction of peritonitis. Serum amyloid assay and lipid peroxidation were significantly lower, and myeloperoxidase assay was higher in the curcumin-treated group at the end of 24 h; thus, curcumin probably demonstrated a neutrophil-mediated immunopotentiation and anti-inflammatory action thereby protecting the animal from endotoxemia-induced multi-organ damage. PMID- 26884659 TI - High-Pressure Water Swelling Sealant Injection Injury to the Hand: a Case Report and Review of the Literature. AB - High-pressure injection injuries (HPII) caused by water swelling sealant are rare at present. The patient generally has small-sized skin lesions, and the misleadingly benign presentation may cause delayed treatment at the early stage of management. In addition, radiographic examination may be underestimated. Subsequently, the inadequate surgical intervention may cause tissue necrosis and poor prognosis. Furthermore, the early recognition of water swelling sealant injected into tissue and emergent surgical intervention are the key to successful management for the patient with HPII caused by injecting water swelling sealant to tissue. PMID- 26884660 TI - Application of Ultrasound-Guided Ilioinguinal/Iliohypogastric Nerve Block in Pediatric Same-Day Surgery. AB - The aim of this study was to evaluate the safety and efficacy of ultrasound guided ilioinguinal/iliohypogastric nerve block (IINB) in pediatric patients undergoing same-day inguinal region surgery. Ninety patients aged 4-6 years, ASA levels I-II, were randomly divided into three groups: U, T, or C (n = 30 each). After basic anesthesia, patients in group U underwent ultrasound-guided IINB, those in group T underwent traditional Schulte-Steinberg IINB, and those in group C (controls) received intravenous anesthesia (ketamine-propofol) only. Patients who remained sensitive to intraoperative stimuli received additional intravenous doses of 1 mg/kg ketamine. Heart rate (HR), mean arterial pressure (MAP), and oxygen saturation (SPO2) were recorded upon entering the operating room (T0), at skin incision (T1), while pulling the hernia sac (T2), during skin closing (T3), and upon awakening (T4) at recovery. HR and MAP at T1, T2, and T4 were higher in group C than those in the other two groups, and recovery time in group C was significantly prolonged (P < 0.05). Group U required significantly lower quantities and frequency of ketamine injection, and pain scores in group U during awakening were lower than those in the other two groups (P < 0.05). Ultrasound guided IINB provided an improved nerve block effect and postoperative analgesia, reduced the amount of local anesthetic required, facilitated more rapid postoperative recovery, and was a safe and effective method of anesthesia. PMID- 26884662 TI - Malrotation of the Intestine in Adult and Colorectal Cancer. AB - Malrotation of the gut is a congenital anomaly and usually presents in childhood. Rarely, it may present in adults. Patients may be asymptomatic, and malrotation is detected during investigations, operation or autopsy. It can cause longstanding abdominal symptoms like pain, dyspepsia or acute abdomen due to volvulus. In adults, malrotation is found with different gastrointestinal malignancies like gastric, hepatobiliary, pancreatic and, in particular, colorectal neoplasms. We are reporting a case of 60-year-old female presented with carcinoma caecum along with malrotation of the gut. It is the first case report from India. We also reviewed documented cases of malrotation associated with colorectal malignancies. A large number of cases have been reported in Japan as compared to rest of the world. Malrotation in adults is probably associated with gastrointestinal malignancies. Possible causes of this association can be genetic factors or gut changes like chronic inflammation. These associations need further study to consider intestinal malrotation as premalignant lesion which may be very important in follow-up of children with malrotation. PMID- 26884663 TI - Spontaneous Disappearance of a Large Chronic Subdural Hematoma: A Pleasant Surprise. AB - We report an extremely rare case of spontaneous complete disappearance of a large chronic subdural hematoma in a 78-year aged man with a significant mass effect and a large midline shift which was diagnosed around 6 weeks before admission. Repeat NCCT of the head in our department to everyone's surprise revealed almost complete spontaneous resolution. Spontaneous resolution of a large chronic subdural hematoma is extremely rare, and the scarce literature whatsoever is available is especially in cases of immune thrombocytopenic purpura where steroids may play a role in the stabilization of neomembranes. Our interest is in this case because of the benign clinical course despite a large size causing severe mass effect and large midline shift. Chronic subdural hematoma is a common entity in the elderly generally seen weeks following minor trauma. Surgical evacuation of a chronic subdural hematoma remains the gold standard treatment, but controversy exists regarding the best surgical option. Spontaneous resolution of a chronic subdural hematoma has also been reported rarely, but mainly in patients with immune thrombocytopenic purpura. PMID- 26884664 TI - Stab Wound in the Skull Treated with a Medial Supraorbital Craniotomy Through an Incision in the Eyebrow-a Minimally Invasive Approach. AB - The eyebrow incision associated with medial supraorbital craniotomy is a minimally invasive alternative approach to the lesions located in the medial anterior cranial fossa. The main advantages of the medial supraorbital craniotomy regarding frontolateral supraorbital craniotomy are the absence of manipulation of the temporal muscle, less risk of injury to the frontotemporal branch of the facial nerve and a more medial view of the anterior structures such as frontal sinus, olfatory groove and frontal lobe. We report a unique case of cranial stab wound in which a piece of the knife stayed in the frontal sinus and removal was performed using the medial supraorbital approach. There were no complications during surgery, the patient reported mild hypoesthesia in the left frontal region and was discharged on the 7th postoperative day. During follow-up after 2 months, good cosmetic result of the surgical wound and preserved sensitivity of the left frontal region were noted. PMID- 26884661 TI - Pancreatic Tuberculosis. AB - Tuberculosis of the pancreas is extremely rare and in most of the cases mimics pancreatic carcinoma. There are a number of case reports on pancreatic tuberculosis with various different presentations, but only a few case series have been published, and most of our knowledge about this disease comes from individual case reports. Patients of pancreatic tuberculosis may remain asymptomatic initially and manifest as an abscess or a mass involving local lymph nodes and usually present with non-specific features. Pancreatic tuberculosis may present with a wide range of imaging findings. It is difficult to diagnose tuberculosis of pancreas on imaging studies as they may present with masses, cystic lesions or abscesses and mass lesions in most of the cases mimic pancreatic carcinoma. As it is a rare entity, it cannot be recommended but suggested that pancreatic tuberculosis should be considered in cases with a large space occupying lesions associated with necrotic peripancreatic lymph nodes and constitutional symptoms. Ultrasonography/computed tomography/endosonography guided biopsy is the recommended diagnostic technique. Most patients achieve complete cure with standard antituberculous therapy. The aims of this study are to review clinical presentation, diagnostic studies, and management of pancreatic tuberculosis and to present our experience of 5 cases of pancreatic tuberculosis. PMID- 26884665 TI - Inflammatory Myofibroblastic Tumor Arising in the Pancreatic Head: a Rare Case Report. AB - Inflammatory myofibroblastic tumor (IMT) is a rare neoplastic lesion with tendency toward local aggressive behavior and recurrence. It is primarily a visceral and soft tissue tumor; however, involvement of pancreas is extremely unusual. A localization in the pancreas needs differentiation from other tumors and chronic pancreatitis. We report a case of inflammatory myofibroblastic tumor arising in pancreatic head in a 32-year-old female who underwent Whipple's procedure. PMID- 26884667 TI - Esophageal Cancer with a Synchronous Multiple Carcinoid of the Duodenal Bulb. AB - Carcinoid tumors of the duodenum are relatively rare. Although they were considered benign lesions, they are now classified malignant, occasionally with poor prognosis. We report a case of esophageal cancer with a synchronous multiple carcinoid of the duodenal bulb. An upper endoscopy visualized with esophageal scan disclosed a stenotic lesion in the lower esophagus and revealed multiple 4- 5-mm-diameter masses which were on the fore wall of the duodenal bulb. The postoperative pathology report confirmed the diagnosis of esophageal squamous cancer and duodenal bulb carcinoid. PMID- 26884666 TI - Thymectomy Cures Diabetes Mellitus and Ameliorates Myasthenia Gravis in a Patient with Thymus Hyperplasia and Hyperthyroidism: Report of a Case. AB - Myasthenia gravis (MG) is a devastating autoimmune disease that involves the acetylcholine receptor (AchR) in the postsynaptic membrane of the neuromuscular junction. It is not uncommon for MG to accompany with other autoimmune diseases and complicate with multiple organ dysfunction. Here, we report on an 18-year-old female patient with a rare case of MG concomitant with thymus hyperplasia, diabetes mellitus, and hyperthyroidism. After full excision of the hyperplastic thymus gland, the patient's muscle weakness was greatly improved and her blood glucose level was restored to normal at the 6-month follow-up. PMID- 26884668 TI - Gastric Cancer and Paraneoplastic Pemphigus. AB - Paraneoplastic pemphigus is a relatively rare but significant acquired autoimmune mucocutaneous disorder that is characterised by diffuse erythema, painful blistering and sores of the skin and mucus membranes. The underlying pathogenesis is believed to be triggered by altered immune system in response to underlying neoplasm. The manifestations can predate, occur at the same time or after the diagnosis of cancer. Associations with gastric cancer have only been reported twice. A 78-year-old lady presented with a month's history of extensive skin lesions that started off as bullous lesions and biopsy revealed bullous pemphigus. Endoscopy for anemia revealed gastric cancer. This case reinforced the need to consider underlying malignancy in elderly patient with new onset dermatological presentation. PMID- 26884669 TI - Clinicoradiological Images of a Rare Type of Lumbar Hernia. AB - A surgeon will rarely see a case of lumbar hernia in his lifetime. They are usually divided into superior and inferior types, but in cases of huge hernias where anatomical delineation is not possible, they are called as diffuse. Further classification into primary and secondary types (on the basis of etiology) and congenital and acquired types is done. Evisceration in a lumbar hernia can be present due to secondary causes but never spontaneously. This is therefore probably the first reported case of a primary eviscerated diffuse lumbar hernia. PMID- 26884670 TI - An Accessory Renal Artery Originating from the Testicular Artery, a Rare Variant. AB - Renal artery variations including their source, number, and course are very common. Accessory renal arteries were discovered frequently on the left side; these arteries entered the upper or lower poles of the kidney. The present cadaver showed a testicular artery origin of the accessory renal artery, which was seldomly described previously. PMID- 26884671 TI - Random Cheek Skin Flap: a Simple Alternative for Intraoral Defects. AB - Oral cavity squamous cell carcinoma is one of the common cancers in India. The lesion usually presents as an ulcer and sometimes as a nodule. A variety of premalignant lesions and submucous fibrosis are common. The mucosal defect after resection needs to be covered. We present a new and simpler way of reconstruction of the oral cavity lining by using extra cheek skin. PMID- 26884672 TI - Innovative Approach to a Frozen Calot's Triangle During Laparoscopic Cholecystectomy. AB - The laparoscopic cholecystectomy is now the "gold standard." In around 2 % of cases, there is a need to convert because of the difficult dissection encountered in the Calot's Triangle, a "frozen Calot's triangle." There is no consensus among surgeons about how to tackle this situation. To lower the conversion rate, there is a continuous attempt made to innovate. The authors present their rationale and experience in 100 difficult cases by creating a retro-gallbladder tunnel and encircling the gallbladder by a gauze for maneuvering. PMID- 26884673 TI - Using Pork Skin as a Practice Medium for Learning Hair Transplantation Techniques. AB - A simple technique using pork skin and excess hair and epidermis harvested from anti-wrinkle surgeries was used to practice hair transplantation techniques. This allows inexperienced physicians to practice and perform the traditional steps of hair transplantation without involving an actual patient in the early stages of perfecting technique. The technique uses pork skin during the procedure, while performing real-time hair transplantation simulation. The surgical result of the procedure can then be visualized, and the training process can be repeated at will; peer evaluation is performed after completion. Results showed that residents that practiced this technique scored consistently better than those without the same training background. Every score increased with practice, and the length of time needed to complete the hair transplantation process decreased. A simple technique using pork skin for practicing hair transplantation technique is a valuable training tool, and gives residents a way to practice sound techniques along with more precise anatomical familiarity for hair transplantation surgery, without the risks associated with training on live patients. PMID- 26884674 TI - Crystallized or Liquid Phenol Application in Pilonidal Sinus Treatment. PMID- 26884675 TI - Gangrenous Jejunogastric Intussusception: Is Reduction advisable? PMID- 26884676 TI - Laparoscopic Hiatal Hernia Repair in 221 Patients: Outcomes and Experience. AB - BACKGROUND AND OBJECTIVES: Hiatal hernia is a common condition often associated with symptomatic gastroesophageal reflux disease (GERD). The objectives of this study were to examine the efficacy and safety of laparoscopic hiatal hernia repair (LHHR) with biologic mesh to reduce and/or alleviate GERD symptoms and associated hiatal hernia recurrence. METHODS: We retrospectively reviewed consecutive LHHR procedures with biologic mesh performed by a single surgeon from July 2009 to October 2014. The primary efficacy outcome measures were relief from GERD symptoms, as measured according to the GERD-health-related quality-of-life (GERD-HRQL) scale and hiatal hernia recurrence. A secondary outcome measure was overall safety of the procedure. RESULTS: A total of 221 patients underwent LHHR with biologic mesh during the study period, and pre- and postoperative GERD-HRQL studies were available for 172 of them. At baseline (preoperative), the mean GERD HRQL score for all procedures was 18.5 +/- 14.4. At follow-up (mean, 14.5 +/- 11.0 months [range, 2.0-56.0]), the score showed a statistically significant decline to a mean of 4.4 +/- 7.5 (P < .0001). To date, 8 patients (3.6%, 8/221) have had a documented anatomic hiatal hernia recurrence. However, a secondary hiatal hernia repair reoperation was necessary in only 1 patient. Most complications were minor (dysphagia, nausea and vomiting). However, there was 1 death caused by a hemorrhage that occurred 1 week after surgery. CONCLUSIONS: Laparoscopic hiatal hernia repair using biologic mesh, both with and without a simultaneous bariatric or antireflux procedure, is an efficacious and safe therapeutic option for management of hiatal hernia, prevention of recurrence, and relief of symptomatic GERD. PMID- 26884677 TI - Phi Class of Glutathione S-transferase Gene Superfamily Widely Exists in Nonplant Taxonomic Groups. AB - Glutathione S-transferases (GSTs) constitute a superfamily of enzymes involved in detoxification of noxious compounds and protection against oxidative damage. GST class Phi (GSTF), one of the important classes of plant GSTs, has long been considered as plant specific but was recently found in basidiomycete fungi. However, the range of nonplant taxonomic groups containing GSTFs remains unknown. In this study, the distribution and phylogenetic relationships of nonplant GSTFs were investigated. We identified GSTFs in ascomycete fungi, myxobacteria, and protists Naegleria gruberi and Aureococcus anophagefferens. GSTF occurrence in these bacteria and protists correlated with their genome sizes and habitats. While this link was missing across ascomycetes, the distribution and abundance of GSTFs among ascomycete genomes could be associated with their lifestyles to some extent. Sequence comparison, gene structure, and phylogenetic analyses indicated divergence among nonplant GSTFs, suggesting polyphyletic origins during evolution. Furthermore, in silico prediction of functional partners suggested functional diversification among nonplant GSTFs. PMID- 26884679 TI - Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination. AB - The goal of this study was to discover a minimally invasive pathway-specific biomarker that is immune to normal cell mRNA contamination for diagnosing head and neck squamous cell carcinoma (HNSCC). Using Elsevier's MedScan natural language processing component of the Pathway Studio software and the TRANSFAC database, we produced a curated set of genes regulated by the signaling networks driving the development of HNSCC. The network and its gene targets provided prior probabilities for gene expression, which guided our CoGAPS matrix factorization algorithm to isolate patterns related to HNSCC signaling activity from a microarray-based study. Using patterns that distinguished normal from tumor samples, we identified a reduced set of genes to analyze with Top Scoring Pair in order to produce a potential biomarker for HNSCC. Our proposed biomarker comprises targets of the transcription factor (TF) HIF1A and the FOXO family of TFs coupled with genes that show remarkable stability across all normal tissues. Based on validation with novel data from The Cancer Genome Atlas (TCGA), measured by RNAseq, and bootstrap sampling, the biomarker for normal vs. tumor has an accuracy of 0.77, a Matthews correlation coefficient of 0.54, and an area under the curve (AUC) of 0.82. PMID- 26884678 TI - HTSFinder: Powerful Pipeline of DNA Signature Discovery by Parallel and Distributed Computing. AB - Comprehensive effort for low-cost sequencing in the past few years has led to the growth of complete genome databases. In parallel with this effort, a strong need, fast and cost-effective methods and applications have been developed to accelerate sequence analysis. Identification is the very first step of this task. Due to the difficulties, high costs, and computational challenges of alignment based approaches, an alternative universal identification method is highly required. Like an alignment-free approach, DNA signatures have provided new opportunities for the rapid identification of species. In this paper, we present an effective pipeline HTSFinder (high-throughput signature finder) with a corresponding k-mer generator GkmerG (genome k-mers generator). Using this pipeline, we determine the frequency of k-mers from the available complete genome databases for the detection of extensive DNA signatures in a reasonably short time. Our application can detect both unique and common signatures in the arbitrarily selected target and nontarget databases. Hadoop and MapReduce as parallel and distributed computing tools with commodity hardware are used in this pipeline. This approach brings the power of high-performance computing into the ordinary desktop personal computers for discovering DNA signatures in large databases such as bacterial genome. A considerable number of detected unique and common DNA signatures of the target database bring the opportunities to improve the identification process not only for polymerase chain reaction and microarray assays but also for more complex scenarios such as metagenomics and next generation sequencing analysis. PMID- 26884681 TI - Harm Experienced from the Heavy Drinking of Family and Friends in the General Population: A Comparative Study of Six Northern European Countries. AB - BACKGROUND: Epidemiological research on alcohol-related harm has long given priority to studies on harm to the drinker. A limitation with this perspective is that it neglects the harm drinking causes to people around the drinker, and thus, it fails to give a full picture of alcohol-related harm in society. AIM: The aim was to compare the prevalence and correlates of experiencing harm from the heavy drinking by family and friends across the Nordic countries and Scotland and to discuss whether potential differences match levels of drinking, prevalence of binge drinking, and alcohol-related mortality. DATA AND METHOD: Data from recent national general population surveys with similar questions on experiences of harms from the drinking of family and friends were collected from Sweden, Finland, Denmark, Norway, Iceland, and Scotland. RESULTS: National estimates of the overall population prevalence of harm from the drinking of family and friends ranged from 14% to 28% across these countries, with the highest prevalence in Finland, Iceland, and Norway and lower estimates for Denmark, Sweden, and Scotland. Across all countries, the prevalence of harm from heavy drinking by family and friends was significantly higher among women and young respondents. CONCLUSION: This study revealed large differences in the prevalence of harm across the study countries, as well as by gender and age, but the differences do not match the variation in population drinking and other indicators of harm. The implications of the findings for future research are discussed. PMID- 26884680 TI - Visualization of Genome Diversity in German Shepherd Dogs. AB - A loss of genetic diversity may lead to increased disease risks in subpopulations of dogs. The canine breed structure has contributed to relatively small effective population size in many breeds and can limit the options for selective breeding strategies to maintain diversity. With the completion of the canine genome sequencing project, and the subsequent reduction in the cost of genotyping on a genomic scale, evaluating diversity in dogs has become much more accurate and accessible. This provides a potential tool for advising dog breeders and developing breeding programs within a breed. A challenge in doing this is to present complex relationship data in a form that can be readily utilized. Here, we demonstrate the use of a pipeline, known as NetView, to visualize the network of relationships in a subpopulation of German Shepherd Dogs. PMID- 26884682 TI - Potential Role of Omega-3 Fatty Acids on the Myogenic Program of Satellite Cells. AB - Skeletal muscle loss is associated with aging as well as pathological conditions. Satellite cells (SCs) play an important role in muscle regeneration. Omega-3 fatty acids are widely studied in a variety of muscle wasting diseases; however, little is known about their impact on skeletal muscle regeneration. The aim of this review is to evaluate studies examining the effect of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid on the regulation of SC proliferation and differentiation. This review highlights mechanisms by which omega-3 fatty acids may modulate the myogenic program of the stem cell population within skeletal muscles and identifies considerations for future studies. It is proposed that minimally three myogenic transcriptional regulatory factors, paired box 7 (Pax7), myogenic differentiation 1 protein, and myogenin, should be measured to confirm the stage of SCs within the myogenic program affected by omega-3 fatty acids. PMID- 26884684 TI - Ochronotic Arthropathy: Two Case Reports from a Developing Country. AB - Alkaptonuria is a rare inborn error of metabolism, which is classified as an orphan disease. It is due to the lack of an enzyme homogentisate 1,2-dioxygenase, which results in an accumulation of homogentisic acid in different areas of the body, including sclera, skin, cardiac valves, articular cartilage of the large joints and intervertebral disks. We present two cases of alkaptonuria resulting in ochronotic arthropathy with advanced secondary generalized osteoarthritis, intervertebral disk calcifications, skin and scleral pigmentation. In these case reports, both patients had symptoms for >10 years before being diagnosed. Conservative management in the form of high-dose ascorbic acid, exercises, and gait aids was offered to both of them, which resulted in some symptomatic improvement in the first case, while the second case was lost to follow-up. Alkaptonuria is a rare disease, and although it does not clearly impact mortality, early diagnosis may improve the quality of life. PMID- 26884683 TI - Glial Tau Pathology in Tauopathies: Functional Consequences. AB - Tauopathies are a class of neurodegenerative diseases characterized by the presence of hyperphosphorylated and aggregated tau pathology in neuronal and glial cells. Though the ratio of neuronal and glial tau aggregates varies across diseases, glial tau aggregates can populate the same degenerating brain regions as neuronal tau aggregates. While much is known about the deleterious consequences of tau pathology in neurons, the relative contribution of glial tau pathology to these diseases is less clear. Recent studies using a number of model systems implicate glial tau pathology in contributing to tauopathy pathogenesis. This review aims to highlight the functional consequences of tau overexpression in glial cells and explore the potential contribution of glial tau pathology in the pathogenesis of neurodegenerative tauopathies. PMID- 26884686 TI - Maternal and Fetal Outcomes in Pregnant Women with a Prosthetic Mechanical Heart Valve. AB - BACKGROUND: Pregnancy is associated with several cardiocirculatory changes that can significantly impact underlying cardiac disease. These changes include an increase in cardiac output, sodium, and water retention leading to blood volume expansion, and reductions in systemic vascular resistance and systemic blood pressure. In addition, pregnancy results in a hypercoagulable state that increases the risk of thromboembolic complications. OBJECTIVES: The aim of this study is to assess the maternal and fetal outcomes of pregnant women with mechanical prosthetic heart valves (PHVs). METHODS: This is a prospective observational study that included 100 pregnant patients with cardiac mechanical valve prostheses on anticoagulant therapy. The main maternal outcomes included thromboembolic or hemorrhagic complications, prosthetic valve thrombosis, and acute decompensated heart failure. Fetal outcomes included miscarriage, fetal death, live birth, small-for-gestational age, and warfarin embryopathy. The relationship between the following were observed: - Maternal and fetal complications and the site of the replaced valve (mitral, aortic, or double)- Maternal and fetal complications and warfarin dosage (<=5 mg, >5 mg)- Maternal and fetal complications and the type of anticoagulation administered during the first trimester. RESULTS: This study included 60 patients (60%) with mitral valve replacement (MVR), 22 patients (22%) with aortic valve replacement (AVR), and 18 patients (18%) with double valve replacement (DVR). A total of 65 patients (65%) received >5 mg of oral anticoagulant (warfarin), 33 patients (33%) received <=5 mg of warfarin, and 2 patients (2%) received low-molecular-weight heparin (LMWH; enoxaparin sodium) throughout the pregnancy. A total of 17 patients (17%) received oral anticoagulant (warfarin) during the first trimester: 9 patients received a daily warfarin dose of >5 mg while the remaining 8 patients received a daily dose of <=5 mg. Twenty-eight patients (28%) received subcutaneous (SC) heparin calcium and 53 patients (53%) received SC LMWH (enoxaparin sodium). Prosthetic valve thrombosis occurred more frequently in patients with MVR (P = 0.008). Postpartum hemorrhage was more common in patients with aortic valve prostheses than in patients with mitral valve prostheses (P = 0.005). The incidence of perinatal death was higher in patients with AVR (P = 0.014). The incidence of live birth was higher in patients with DVR (P = 0.012). The incidence of postpartum hemorrhage was higher in patients who received a daily dose of >5 mg of warfarin than in patients who received <=5 mg of warfarin (P = 0.05). The incidence of spontaneous abortion was also higher in patients receiving >5 mg of warfarin (P <= 0.001), while the incidence of live births was higher in patients receiving <=5 mg of warfarin (P = 0.008). There was a statistically significant difference between the anticoagulant received during the first trimester and cardiac outcomes. Specifically, patients on heparin developed more heart failure (P = 0.008), arrhythmias (P = 0.008), and endocarditis (P = 0.016). There was a statistically significant relationship between heparin shifts during the first trimester and spontaneous abortion (P = 0.003). CONCLUSION: Warfarin use during the first trimester is safer for the mother but is associated with more fetal loss, especially in doses that exceed 5 mg. The incidence of maternal complications is greater in women who receive LMWH or unfractionated heparin during the first trimester, especially prosthetic valve thrombosis, although the fetal outcome is better because heparin does not cross the placenta. PMID- 26884685 TI - Acute Coronary Syndromes in Women: Recent Treatment Trends and Outcomes. AB - In the USA and internationally, women experience farranging differences with respect to acute coronary syndrome (ACS) and myocardial infarction (MI). Women suffer from more comorbidities than men, such as smoking, obesity, hypertension, diabetes, and poor mental health. They some-times exhibit atypical MI presentation symptoms and are overall less likely to present with chest pain. Women are more likely than men to encounter delays between the onset of symptoms and arrival at the hospital or to guideline treatment. The use of various surgical and pharmacological treatments, including revascularization approaches, also differs. Women, on average, have worse outcomes than men following MI, with more complications, higher mortality rates, and poorer recovery. Internationally, outcomes are similar despite various differences in health care and culture in non-US countries. In this review, we detail differences regarding ACS and MI in women, describing their complex correlations and discussing their possible causes. Educational approaches that are tailored to women might help to reduce the incidence of ACS and MI, as well as outcomes following hospitalization. Although outcomes following acute MI have been improving over the years, women may require special consideration in order to see continued improvement. PMID- 26884687 TI - Neutrophil/Lymphocyte Ratio as a Predictor of In-Hospital Major Adverse Cardiac Events, New-Onset Atrial Fibrillation, and No-Reflow Phenomenon in Patients with ST Elevation Myocardial Infarction. AB - BACKGROUND: Neutrophil/lymphocyte (N/L) ratio represents the balance between neutrophil and lymphocyte counts in the body and can be utilized as an index for systemic inflammatory status. The no-reflow phenomenon is defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction. Systemic inflammatory status has been associated with new-onset atrial fibrillation (NOAF) as well as no-reflow. AIM: To evaluate the predictive value of N/L ratio for in-hospital major adverse events, NOAF, and no-reflow in patients with ST elevation myocardial infarction (STEMI). PATIENTS: Two hundred consecutive patients with STEMI presenting to Alexandria Main University Hospital and International Cardiac Center Hospital, Alexandria, Egypt, from April 2013 to October 2013 were included in this study. METHODS: Laboratory investigation upon admission included complete blood count with mean platelet volume (MPV) and N/L ratio, and random plasma glucose (RPG) level. The results of coronary angiography indicating the infarct related artery (IRA), initial thrombolysis in myocardial infarction (TIMI) flow in the IRA, and the TIMI flow after stenting were recorded. The patients were studied according to the presence of various clinical and laboratory variables, such as age, gender, pain-to-balloon time, location of the infarction, RPG level and complete blood count including N/L ratio and MPV on admission, and initial TIMI flow in the IRA. They were also evaluated for the final TIMI flow after the primary percutaneous coronary intervention, incidence of NOAF, and the incidence of in-hospital major adverse cardiac events (MACE). RESULTS: The incidence rate of no-reflow, NOAF, and in-hospital MACE was 13.2%, 8%, and 5%, respectively, with cardiac death as the predominant form of in-hospital MACE. The group of no reflow, NOAF, and/or MACE showed significantly older age (62.29 +/- 7.90 vs 56.30 +/- 10.34, P = 0.014), longer pain-to-balloon time (15.90 +/- 7.87 vs 6.08 +/- 3.82 hours, P < 0.001), higher levels of RPG, N/L ratio (8.19 +/- 3.05 vs 5.44 +/ 3.53, P, 0.001), and MPV (11.90 +/- 2.09 vs 8.58 +/- 1.84 fL, P < 0.001) on admission. After adjustment of confounding factors, the independent predictors of NOAF, no-reflow, and in-hospital MACE were higher N/L ratio (odds ratio [OR] = 3.5, P = 0.02) and older age (OR = 3.1, P = 0.04). CONCLUSIONS: Older patient age, longer pain-to-balloon time, hyperglycemia, higher N/L ratio, and MPV on admission are useful predictive factors for the occurrence of no-reflow postprimary percutaneous coronary intervention, NOAF, and/or in-hospital MACE. N/L ratio is a new strong independent predictor of no-reflow, NOAF, and/or in hospital MACE in patients with STEMI. The use of this simple routine biomarker may have a potential therapeutic implication in preventing NOAF and improving prognosis in STEMI revascularized patients. PMID- 26884689 TI - Evaluation of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis: single center experience over a one-year period. AB - AIM: This study aimed to evaluate the demographic, clinical, laboratory properties of patients with macrophage activation syndrome and treatment outcomes. MATERIAL AND METHODS: The data of the patients who were diagnosed with macrophage activation syndrome secondary to systemic juvenile idiopathic arthritis between June 2013-May 2014 were evaluated by screening patient records. RESULTS: Ten patients with macrophage activation syndrome were followed up in one year. The mean age at the time of diagnosis was found to be 7.6+/-4.5 years. The most common clinical finding at presentation (80%) was increased body temperature. Hepatosplenomegaly was found in half of the patients. The most common hematological finding (90%) was anemia. The mean erythrocyte sedimentation rate was found to be 71.8+/-36.2 mm/h, whereas it was measured to be lower (31.2+/-25.2 mm/h) at the time of the diagnosis of macrophage activation syndrome. Increased ferritin level was found in all of our patients (the mean ferritin level was found to be 23 957+/-15 525 ng/mL). Hypertriglyceridemia was found in nine patients (90%). The mean triglyceride level was found to be 397+/ 332 mg/dL. Systemic steroid treatment was administered to all patients. Cyclosporine A was given to eight patients (80%), canakinumab was given to four patients (40%) and anakinra was given to five patients (50%). Plasmapheresis was performed in two patients. Improvement was found in all patients except for one patient. The patient in whom no improvement was observed showed a chronic course. CONCLUSIONS: The diagnosis of macrophage activation syndrome should be considered in presence of sudden disturbance in general condition, resistant high fever and systemic inflammation findings in children with active rheumatic disease. Complete recovery can be provided with early and efficient treatment in macrophage activation syndrome which develops secondary to systemic juvenil idiopathic arthritis. PMID- 26884688 TI - Diagnostic approach and current treatment options in childhood vasculitis. AB - All inflammatory changes in the vessel wall are defined as vasculitis. Pediatric vasculitis may present with different clinical findings. Although Henoch Schonlein purpura which is the most common pediatric vasculitis generally recovers spontaneously, it should be monitorized closely because of the risk of renal failure. Although Kawasaki disease is easy to diagnose with its classical findings, the diagnosis may be delayed in case of incomplete Kawasaki disease. Kawasaki disease should be considered especially in infants in case of prolonged fever even if the criteria are not fully met and intravenous immunoglobulin treatment should be administered without delay in order to prevent development of coronary artery aneurism. Reaction at the site of administration of Bacillus Calmette-Guerin (BCG) vaccine may be observed as commonly as cervical lymphadenopathy in Kawasaki disease and may be used as a valuable finding in suspicious cases. Although anti-neutrophil cytoplasmic antibody-associated vasculitides are rare in children, renal involvement is more common and progression is more severe compared to adults. Hence, efficient and aggressive treatment is required. Takayasu's arteritis is observed commonly in young adult women and rarely in adolescent girls. Therefore, a careful physical examination and blood pressure measurement should be performed in addition to a detailed history in daily practice. In children with unexplained neurological findings, cerebral vasculitis should be considered in the absence of other systemic vasculitides and necessary radiological investigations should be performed in this regard. This review will provide an insight into the understanding of pediatric vasculitis, current diagnostic approaches and prognosis by the aid of new studies. PMID- 26884690 TI - Percutaneous endoscopic gastrostomy in children: a single center experience. AB - AIM: The aim of this study was to evaluate the demographic data and complication rates in children who had undergone percutaneous endoscopic gastrostomy in a three-year period in our Division of Pediatric Gastroenterology and to interrogate parental satisfaction. MATERIAL AND METHODS: The demographic data, complications and follow-up findings of the patients who had undergone percutaneous endoscopic gastrostomy between March 2011 and March 2014 were examined retrospectively using medical files. RESULTS: Forty seven percutaneous endoscopic gastrostomy and percutaneous endoscopic gastrostomy related procedures were performed in 34 children during a three-year period. The median age of the patients was 2.25 years (3 months-16 years, first and third quartiles=1.0-6.0) and the mean body weight was 13.07+/-8.6 kg (3 kg-47 kg). Before percutaneous endoscopic gastrostomy procedure, the mean weight z score was -2.26+/-1.2 (-5-0) and the mean height z score was -2.25+/-0.96 (-3.85-0.98). The follow-up mean height and weight Z scores at the 12(th) month after the percutaneous endoscopic gastrostomy procedure could be reached in 24 patients. A significant increase in the mean weight Z score from -2.41 to -1,07 (p=0.000) and in the mean height Z score from -2.29 to -1.99 (p=0.000) was found one year after percutaneous endoscopic gastrostomy catheter was placed in these 24 patients. Patients with neurological and metabolic diseases constituted the majority (64.7% and 26.5% respectively). Peritoneal leakage of food was detected in one patient and local stoma infections were detected in three patients after the procedure. During the follow up period, "Buried bumper syndrome" was observed in one patient. Following percutaneous endoscopic gastrostomy, the number of patients using anti-reflux medication increased from 16 (47.1%) to 18 (52.9%) (p=0.62). One patient with cerebral palsy who had aspiration pneumonia after percutaneous endoscopic gastrostomy insertion had undergone Nissen fundoplication. Percutaneous endoscopic gastrostomy tube was removed in a patient. The parents had positive views related with percutaneous endoscopic gastrostomy after the procedure. CONCLUSIONS: Percutaneous endoscopic gastrostomy is a substantially successful and reliable method in infants as well as in children and adolescents. The parents had positive views related with percutaneous endoscopic gastrostomy after the procedure. PMID- 26884691 TI - Evaluation of epidemiological and clinical features of influenza and other respiratory viruses. AB - AIM: In our study, we aimed to clinically and epidemiologically evaluate respiratory tract infections the viral agents of which were detected by molecular methods and to compare influenza and other respiratory tract viruses in this context. MATERIAL AND METHODS: The records of 178 patients aged above 2 years who presented to pediatric emergency outpatient clinic with fever and respiratory tract infection findings between December 2013 and April 2014 were examined retrospectively. RESULTS: At least one respiratory tract pathogen was detected by polymerase chain reaction in 78.6% (n=140) of the patients: influenza A 33.5%, influenza B 16.4%, respiratory syncytial virus 9.2%, adenovirus 7.8%, rhinovirus 7.1%, coronavirus 7.1%, human metapneumovirus 5.7%, human bocavirus 5.7%, parainfluenza virus 3.5%, coinfection 2.8%. The mean age of the patients was 6.3+/-3.6 years. Sixty-nine patients (49.2%) were aged between 2 and 5 years. Seventy-one patients (50.7%) were aged 5 years and above. Upper respiratory tract infection was found with a rate of 65.7% and lower respiratory tract infection was found with a rate of 34.2%. It was observed that the distribution of respiratory tract viruses showed variance by age groups. Influenza A infection was observed with the highest rate in both age groups. Influenza B was the second leading agent (p=0.008) above the age of 5 years and respiratory syncytial virus was the second leading agent in the 2-5 year age group (p=0.003). Influenza viruses were detected in 55.9% of 118 patients who were found to be compatible with the definition of "influenza-like illness" specified in the Center for Disease Control and Prevention guidelines and other viral agenst were detected in 44%. No difference could be found between the clinical pictures and radiological findings caused by influenza and other respiratory tract viruses. CONCLUSIONS: In this study, it was concluded that influenza and other respiratory viruses can not be differentiated definitely by clinical and radiological findings, though there are some differences. PMID- 26884692 TI - Comparison of the efficiencies of esophageal manometry, vector volume analysis and esophagus pH monitoring in the diagnosis of gastroesophageal reflux. AB - AIM: In this study, we aimed to compare the superiorities of esophageal manometry, vector volume analysis and 24-hour pH meter studies in showing gastroesophageal reflux disease. MATERIAL AND METHODS: The files of the patients who presented to pediatric surgery and pediatric gastroenterology outpatient clinics of our hospital with suspicious gastroesophageal reflux disease between 2011 and 2012 and who were investigated were examined and 21 patients whose investigations had been completed were included in the study. The patients were evaluated by treatment method and were divided into three groups as Group 1 who were followed up with medical treatment, Group 2 in whom surgical intervention was performed and Group 3 who were not treated. Chi-square test was used in evaluation of the categorical variables, Kruskal Wallis test was used in comparison of the mean values between the groups and Dunn test was used in subgroup analyses when Kruskal Wallis test was found to be significant. A p value of <0.05 was considered statistically significant. RESULTS: Thirteen of 21 patients included in the study were female and eight were male. The mean age of the patients was 5.71 years (one-16 years). In the 24-hour pH monitoring study, the mean reflux index was found to be 48.7% in Group 1, 42.4% in Group 2 and 28.3% in Group 3. In esophageal manometry studies, the pressure difference at lower esophageal sphincter (LES) was found to be 13,4 cm H2O in Group 1, 31.8 cm H2O in Group 2 and 4.3 cmH2O in Group 3. In vector volume analyses, the mean vector volume was calculated to be 96.01 cm(3) in Group 1, 2 398.9 cm(3) in Group 2 and 196.3 cm(3) in Group 3. In the 24-hour pH monitoring study, a statistically significant difference (p<0.05) was found in terms of showing reflux, whereas statistical significance could not be shown in terms of need for surgical treatment or need for medical treatment in any other method (p>0.05). CONCLUSIONS: Twenty-four-hour pH monitoring was found to be efficient in making a diagnosis of gastroesophageal reflux disease, whereas esophageal manometry and vector volume analyses were not found to be efficient. PMID- 26884694 TI - Our patients followed up with a diagnosis of neurogenic pulmonary edema. AB - Neurogenic pulmonary edema is a clinical situation which developes as a result of central nervous system injury. It is rare in the childhood. Neurogenic pulmonary edema is a clinical diagnosis. Although the pathogenesis is not elucidated well, there is increase in pulmonary interstitial and alveolar fluid. The main principle in treatment of neurogenic pulmonary edema is supportive treatment and decreasing intracranial pressure as in acute respiratory distress syndrome. In this article, clinical properties of our two patients diagnosed with neurogenic pulmonary edema developed as a result of central nervous system injury are presented. PMID- 26884693 TI - Foreign body ingestion in children. AB - AIM: Foreign bodies ingested by the oral route enter into the gastrointestinal tract and are considered a significant health problem in the childhood. In this study, we evaluated the pediatric patients who presented to our hospital with the complaint of ingestion of foreign body. MATERIAL AND METHODS: The hospital records of all children who presented to our clinic because of ingestion of foreign body between January 2008 and January 2015 were examined retrospectively. The complaints at admission, the types of foreign bodies ingested, the localization of the foreign body in the gastrointestinal tract and the approaches and treatment methods used were examined. RESULTS: Thirty-six (56%) of 64 patients included in the study were male and 28 (44%) were female and the mean age was 5.7+/-4.6 years (10 months-17 years). Thirty eight (59%) of 64 children who were included in the assessment were below the age of five years. The most common complaint at presentation was parental recognition of the ingested object and dysphagia. The most commonly ingested foreign bodies included coins, sewing pins, safety pins and hairclips. Nail clipper detected in the stomach, sewing pin which penetrated through the duodenal wall and stuck to hepatic parenchyma were the first pediatric cases in the literature. Upper esophagus was the most common location for foreign bodies. Endoscopic examinations were performed in 55 of 64 children. CONCLUSIONS: Early detection and treatment of ingested foreign bodies in the upper gastrointestinal system is important in terms of preventing possible complications. In our study, the most frequent foreign bodies detected in the upper digestive tract were coins and they were most frequently detected in the upper esophagus. Most of our patients were below the age of five years. Flexible endoscopic method was used commonly for treatment. PMID- 26884695 TI - Hair-thread tourniquet syndrome in a preterm baby. AB - Hair-thread tourniquet syndrome is a rare disorder characterized by the encircling of an appendage by a hair or thread. It usually occurs in children under the age of one year. The tourniquet syndrome may occur in different parts of the body, particularly in toes, fingers, penis, clitoris, labia, neck and uvula. It is an emergency condition that induces progressive edema, ischaemia and tissue necrosis and can lead to autoamputation of digits or other strangulated structures. Emergency treatment is careful removal of the constricting fiber. We report a preterm newborn with hair-thread tourniquet syndrome affecting multiple toes born at the 28th gestational week with the aim of preventing potential complications by increasesing awareness of the condition. PMID- 26884696 TI - Seizures due to high dose camphor ingestion. AB - Camphor is a cyclic ketone of the hydro aromatic terpene group. Today it is frequently used as a prescription or non-prescription topical antitussive, analgesic, anesthetic and antipruritic agent. Camphor which is considered an innocent drug by parents and physicians is a common household item which can lead to severe poisoning in children even when taken in small amounts. Neurotoxicity in the form of seizures can ocur soon after ingestion. A two-year old female patient who presented with a complaint of generalized tonic-clonic seizures after oral ingestion of camphor is presented. PMID- 26884697 TI - West syndrome due to vitamin B12 deficiency. AB - Vitamin B12 is one of the essential vitamins affecting various systems of the body. Vitamin B12 deficiency in infants often produces haematological and neurological deficits including macrocyticanaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor andseizures. In this article, we report the case of a six-month-old male patient diagnosed with West syndrome associated with vitamin B12 deficiency. Although the patient had no evidence of macrocytic anemia in complete blood count, we measured the level of vitamin B12 because the patient had hypotonicity and found it to be low. No other problem was found in the other investigations directed to the etiology of West syndrome. He was being exclusively breast-fed and vitamin B12 deficiency was related with nutritional inadequacy of his mother. Vitamin B12 deficiency should be considered in the differential diagnosis of patients presenting with different neurological findings. In addition, vitamin B12 deficiency should be considered as a rare cause in West syndrome which has a heterogeneous etiology. PMID- 26884698 TI - Renal involvement in tuberous sclerosis complex. PMID- 26884699 TI - Manual for proposing a Part of the List of Available Names (LAN) in Zoology. PMID- 26884700 TI - Horst Aspock, encyclopedist and entomologist extraordinaire - a personal appreciation. AB - The paper provides an overview of the life and work of Prof. Dr. Horst Aspock, the doyen of neuropterology, on the occasion of his 75(th) birthday. It particularly emphasizes his outstanding contributions to the development of neuropterology since the 1960s. PMID- 26884701 TI - One new species and two new records of the genus Aeolothrips from Iran (Insecta, Thysanoptera, Aeolothripidae). AB - Aeolothrips gundeliae sp. n. is described, and two bicolored species of the same genus, Aeolothrips ericae Bagnall and Aeolothrips albithorax Pelikan are newly reported from northeast of Iran. Diagnostic characters are provided for each species as well as illustrations to distinguish these species. PMID- 26884702 TI - The Taxonomic Significance of ducts in the corolla lobes of Vernonia (Vernonieae: Asteraceae). AB - The multiple longitudinal ducts in the corolla lobes found in the closely related genera Vernonia, Vernonanthura and Trepadonia are microscopically studied and illustrated. The lack of such ducts in the two South American species that have until now been retained in Vernonia indicates that they should probably be excluded from the genus. PMID- 26884703 TI - Marrubium eriocephalum (Lamiaceae); a species new to the flora of Turkey, with contributions to its taxonomy. AB - Marrubium eriocephalum (Lamiaceae) is described as a new record for the Flora of Turkey (B9 Van). A detailed morphological description, photographs, distribution map, and pollen and nutlet morphology of this new record are given. PMID- 26884704 TI - Floristic survey of herbaceous and subshrubby aquatic and palustrine angiosperms of Virua National Park, Roraima, Brazil. AB - We provide and discuss a floristic survey of herbaceous and subshrubby aquatic and palustrine angiosperms of Virua National Park (VNP). The VNP is located in the northern Amazon basin and displays phytophysiognomies distributed in a mosaic where these plants occur, as flooded forests, hydromorphic white-sand savannas, "buritizais" and waterbodies. After expeditions between February/2010 and January/2015 and the analysis of specimens from regional herbaria, we list 207 species of herbaceous and subshrubby aquatic and palustrine angiosperms for the VNP, distributed in 85 genera in 37 families. We recorded six new occurrences for Brazil, two for the northern Brazilian region and 21 for Roraima state. These new occurrences, added to the other species listed here, highlight the floristic similarity between the study site and the Guiana Shield, an adjacent phytogeographical unit and geologically related to the origin of white-sand savannas. PMID- 26884705 TI - A revision of the genus Osmoxylon (Araliaceae) in Palau, including two new species. AB - Osmoxylon Miq. (Araliaceae) is revised for Palau, Micronesia including descriptions of two new taxa Osmoxylon leidichii Costion, sp. nov. and Osmoxylon ngardokense Costion, sp. nov. Full descriptions are provided for all four Palau species, along with diagnostic field keys. PMID- 26884706 TI - A comprehensive checklist of vascular epiphytes of the Atlantic Forest reveals outstanding endemic rates. AB - Knowledge of the geographic distribution of plants is essential to underpin the understanding of global biodiversity patterns. Vascular epiphytes are important components of diversity and functionality of Neotropical forests but, unlike their terrestrial counterparts, they are under-represented in large-scale diversity and biogeographic analyses. This is the case for the Atlantic Forest - one of the most diverse and threatened biomes worldwide. We provide the first comprehensive species list of Atlantic Forest vascular epiphytes; their endemism patterns and threatened species occurrence have also been analyzed. A list with 2,256 species of (hemi-)epiphytes - distributed in 240 genera and 33 families - is presented based on the updated Brazilian Flora Checklist. This represents more than 15% of the total vascular plant richness in the Atlantic Forest. Moreover, 256 species are included on the Brazilian Red List. More than 93% of the overall richness is concentrated in ten families, with 73% represented by Orchidaceae and Bromeliaceae species alone. A total of 78% of epiphytic species are endemic to the Atlantic Forest, in contrast to overall vascular plant endemism in this biome estimated at 57%. Among the non-endemics, 13% of epiphytic species also occur either in the Amazon or in the Cerrado - the other two largest biomes of Brazil - and only 8% are found in two or more Brazilian biomes. This pattern of endemism, in addition to available dated phylogenies of some genera, indicate the dominance of recent radiations of epiphytic groups in the Atlantic Forest, showing that the majority of divergences dating from the Pliocene onwards are similar to those that were recently reported for other Neotropical plants. PMID- 26884707 TI - On the identity of Blanco's Cissus frutescens and its correct name in Melicope (Rutaceae) with neotypification of Cissus arborea Blanco. AB - The names Cissus frutescens and Cissus arborea have a long history of confusion. Cissus frutescens Blanco belongs to the genus Melicope (Rutaceae) and we herein correct a nomenclatural mistake made by T.G. Hartley in the revision of Melicope. The name Melicope confusa (Merr.) P.S. Liu was accepted for this taxon by Hartley. However, Cissus frutescens Blanco represents the earliest name for this entity and a new combination, Melicope frutescens (Blanco) Appelhans & J.Wen is herein proposed. Neotypification of Cissus arborea Blanco is also provided. PMID- 26884708 TI - Encyclia inopinata (Orchidaceae, Laeliinae) a new species from Mexico. AB - A new species of Encyclia from Mexico, Encyclia inopinata, is described and illustrated. This species is similar to Encyclia diota but it can be distinguished by its usually more robust plants with 2-3 leaves per pseudobulb and its flowers with longer and narrower sepals (1.8+/-0.1 * 0.63+/-0.03 cm in Encyclia inopinata versus 1.48 +/-0.14 * 0.65+/-0.06 cm in Encyclia diota) and petals (1.7+/-0.05 * 0.59+/-0.05 cm in Encyclia inopinata vs. 1.36 +/-0.19 * 0.81+/-0.13 cm in Encyclia diota), and the labellum with narrower lateral lobes (0.18+/-0.02 cm in Encyclia inopinata vs. 0.41+/-0.10 cm in Encyclia diota). Other characters that differentiate these two species are the coriaceous sepals, pink callus, and white anther of Encyclia inopinata (versus fleshy-leathery sepals, white callus, and yellow anther of Encyclia diota). The new species can be found in deciduous forests along the Pacific slope of Oaxaca state, near of the border with Guerrero state, at about 1200 m. It blooms between March and July. PMID- 26884709 TI - Homalium glandulosum (Salicaceae), a new species from Vu Quang National Park, North Central Vietnam. AB - Homalium glandulosum Tagane & V. H. Nguyen, from Vu Quang National Park in northern Vietnam, is newly described. This species is characterized by distinct glands, often stalked, at the base of the lamina and along the margin of the stipules and bracteoles. Illustrations, DNA barcodes of the two regions of rbcL and matK, and a key to the species of Homalium in Vietnam are also provided. PMID- 26884710 TI - Two new species of Siphocampylus (Campanulaceae, Lobelioideae) from the Central Andes. AB - Two species of Siphocampylus (Campanulaceae: Lobelioideae) from the Central Andes of Peru and Bolivia are described, illustrated, and discussed with reference to related species. One species, Siphocampylus antonellii, is endemic to high elevation grasslands of Calca, Peru, while the second, Siphocampylus siberiensis, is endemic to cloud forests of Cochabamba, Bolivia. Both species are robust shrubs that produce tubular pink flowers that are likely pollinated by hummingbirds. PMID- 26884711 TI - Typification of Zapalowicz's names in Aconitum section Aconitum. AB - Hugo Zapalowicz described and named 27 taxa in Aconitum sect. Aconitum. Their names are typified here. Two of them (Aconitum berdaui, Aconitum bucovinense) are deemed correct for currently accepted species of the Carpathians, 24 are reduced to synonymy under five taxa, and for one no original material has been located. The correct place and exact date of their publication, which differs from those usually assumed, have been ascertained by bibliographic verification and the study of archival documents. PMID- 26884712 TI - "DNA Binding Region" of BRCA1 Affects Genetic Stability through modulating the Intra-S-Phase Checkpoint. AB - The breast cancer associated gene 1 (BRCA1) contains 3 domains: an N-terminal RING domain with ubiquitin E3 ligase activity, C-terminal BRCT protein interaction domain and a central region. RING and BRCT domains are well characterized, yet the function of the central region remains unclear. In this study, we identified an essential DNA binding region (DBR: 421-701 amino acids) within the central region of human BRCA1, and found that BRCA1 brings DNA together and preferably binds to splayed-arm DNA in a sequence-independent manner. To investigate the biological role of the DBR, we generated mouse ES cells, which lack the DBR (DeltaDBR) by using the TALEN method. The DeltaDBR cells exhibited decreased survival as compared to the wild type (WT) cells treated with a PARP inhibitor, however they have an intact ability to conduct DNA repair mediated by homologous recombination (HR). The DeltaDBR cells continued to incorporate more EdU in the presence of hydroxyurea (HU), which causes replication stress and exhibited reduced viability than the WT cells. Moreover, phosphorylation of CHK1, which regulates the intra-S phase checkpoint, was moderately decreased in DeltaDBR cells. These data suggest that DNA binding by BRCA1 affects the stability of DNA replication folks, resulting in weakened intra S-phase checkpoint control in the DeltaDBR cells. The DeltaDBR cells also exhibited an increased number of abnormal chromosome structures as compared with WT cells, indicating that the DeltaDBR cells have increased genetic instability. Thus, we demonstrated that the DBR of BRCA1 modulates genetic stability through the intra-S-phase checkpoint activated by replication stress. PMID- 26884713 TI - Nucleophosmin Mutants Promote Adhesion, Migration and Invasion of Human Leukemia THP-1 Cells through MMPs Up-regulation via Ras/ERK MAPK Signaling. AB - Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been defined as a unique subgroup in the new classification of myeloid neoplasm, and the AML patients with mutated NPM1 frequently present extramedullary infiltration, but how NPM1 mutants regulate this process remains elusive. In this study, we found that overexpression of type A NPM1 gene mutation (NPM1-mA) enhanced the adhesive, migratory and invasive potential in THP-1 AML cells lacking mutated NPM1. NPM1-mA had up-regulated expression and gelatinolytic matrix metalloprotease-2 (MMP 2)/MMP-9 activity, as assessed by real-time PCR, western blotting and gelatin zymography. Following immunoprecipitation analysis to identify the interaction of NPM1-mA with K-Ras, we focused on the effect of NPM1-mA overexpression on the Ras/Mitogen-activated protein kinase (MAPK) signaling axis and showed that NPM1 mA increased the MEK and ERK phosphorylation levels, as evaluated by western blotting. Notably, a specific inhibitor of the ERK/MAPK pathway (PD98059), but not p38/MAPK, JNK/MAPK or PI3-K/AKT inhibitors, markedly decreased the cell invasion numbers in a transwell assay. Further experiments demonstrated that blocking the ERK/MAPK pathway by PD98059 resulted in reduced MMP-2/9 protein levels and MMP-9 activity. Additionally, NPM1-mA overexpression had down regulated gene expression and protein production of tissue inhibitor of MMP-2 (TIMP-2) in THP-1 cells. Furthermore, evaluation of gene expression data from The Cancer Genome Atlas (TCGA) dataset revealed that MMP-2 was overexpressed in AML patient samples with NPM1 mutated and high MMP-2 expression associated with leukemic skin infiltration. Taken together, our results reveal that NPM1 mutations contribute to the invasive potential of AML cells through MMPs up regulation via Ras/ERK MAPK signaling pathway activation and offer novel insights into the potential role of NPM1 mutations in leukemogenesis. PMID- 26884714 TI - Recent Developments in Using Advanced Sequencing Technologies for the Genomic Studies of Lignin and Cellulose Degrading Microorganisms. AB - Lignin is a complex polyphenyl aromatic compound which exists in tight associations with cellulose and hemicellulose to form plant primary and secondary cell wall. Lignocellulose is an abundant renewable biomaterial present on the earth. It has gained much attention in the scientific community in recent years because of its potential applications in bio-based industries. Microbial degradation of lignocellulose polymers was well studied in wood decaying fungi. Based on the plant materials they degrade these fungi were classified as white rot, brown rot and soft rot. However, some groups of bacteria belonging to the actinomycetes, alpha-proteobacteria and beta-proteobacteria were also found to be efficient in degrading lignocellulosic biomass but not well understood unlike the fungi. In this review we focus on recent advancements deployed for finding and understanding the lignocellulose degradation by microorganisms. Conventional molecular methods like sequencing 16s rRNA and Inter Transcribed Spacer (ITS) regions were used for identification and classification of microbes. Recent progression in genomics mainly next generation sequencing technologies made the whole genome sequencing of microbes possible in a great ease. The whole genome sequence studies reveals high quality information about genes and canonical pathways involved in the lignin and other cell wall components degradation. PMID- 26884715 TI - Caspase-3/7-mediated Cleavage of beta2-spectrin is Required for Acetaminophen induced Liver Damage. AB - The ubiquitously expressed beta2-spectrin (beta2SP, SPTBN1) is the most common non-erythrocytic member of the beta-spectrin gene family. Loss of beta2-spectrin leads to defects in liver development, and its haploinsufficiency spontaneously leads to chronic liver disease and the eventual development of hepatocellular cancer. However, the specific role of beta2-spectrin in liver homeostasis remains to be elucidated. Here, we reported that beta2-spectrin was cleaved by caspase 3/7 upon treatment with acetaminophen which is the main cause of acute liver injury. Blockage of beta2-spectrin cleavage robustly attenuated beta2-spectrin specific functions, including regulation of the cell cycle, apoptosis, and transcription. Cleaved fragments of beta2-spectrin were physiologically active, and the N- and C-terminal fragments retained discrete interaction partners and activity in transcriptional regulation and apoptosis, respectively. Cleavage of beta2-spectrin facilitated the redistribution of the resulting fragments under conditions of liver damage induced by acetaminophen. In contrast, downregulation of beta2-spectrin led to resistance to acetaminophen-induced cytotoxicity, and its insufficiency in the liver promoted suppression of acetaminophen-induced liver damage and enhancement of liver regeneration. CONCLUSIONS: beta2-Spectrin, a TGF-beta mediator and signaling molecule, is cleaved and activated by caspase 3/7, consequently enhancing apoptosis and transcriptional control to determine cell fate upon liver damage. These findings have extended our knowledge on the spectrum of beta2-spectrin functions from a scaffolding protein to a target and transmitter of TGF-beta in liver damage. PMID- 26884716 TI - Lysozyme Mutants Accumulate in Cells while Associated at their N-terminal Alpha domain with the Endoplasmic Reticulum Chaperone GRP78/BiP. AB - Amyloidogenic human lysozyme variants deposit in cells and cause systemic amyloidosis. We recently observed that such lysozymes accumulate in the endoplasmic reticulum (ER) with the ER chaperone GRP78/BiP, accompanying the ER stress response. Here we investigated the region of lysozyme that is critical to its association with GRP78/BiP. In addition to the above-mentioned variants of lysozyme, we constructed lysozyme truncation or substitution mutants. These were co-expressed with GRP78/BiP (tagged with FLAG) in cultured human embryonic kidney cells, which were analyzed by western blotting and immunocytochemistry using anti lysozyme and anti-FLAG antibodies. The amyloidogenic variants were confirmed to be strongly associated with GRP78/BiP as revealed by the co-immunoprecipitation assay, whereas N-terminal mutants pruned of 1-41 or 1-51 residues were found not to be associated with the chaperone. Single amino acid substitutions for the leucine array along the alpha-helices in the N-terminal region resulted in wild type lysozyme remaining attached to GRP78/BiP. These mutations also tended to show lowered secretion ability. We conclude that the N-terminal alpha-helices region of the lysozyme is pivotal for its strong adhesion to GRP78/BiP. We suspect that wild-type lysozyme interacts with the GRP at this region as a step in the proper folding monitored by the ER chaperone. PMID- 26884717 TI - Cyclosporine A Suppressed Glucose Oxidase Induced P53 Mitochondrial Translocation and Hepatic Cell Apoptosis through Blocking Mitochondrial Permeability Transition. AB - P53 is known as a transcription factor to control apoptotic cell death through regulating a series of target genes in nucleus. There is accumulating evidences show that p53 can directly induce cell apoptosis through transcription independent way at mitochondria. However, the mechanism by which p53 translocation into mitochondria in response to oxidative stress remains unclear. Here, glucose oxidase (GOX) was used to induce ROS generation in HepG2 cells and liver tissues of mice. The results showed that p53 was stabilized and translocated to mitochondria in a time and dose dependent manner after GOX exposure. Interestingly, as an inhibitor of mitochondrial permeability transition, cyclosporine A (CsA) was able to effectively reduce GOX mediated mitochondrial p53 distribution without influencing on the expression of p53 target genes including Bcl-2 and Bax. These indicated that CsA could just block p53 entering into mitochondria, but not affect p53-dependent transcription. Meanwhile, CsA failed to inhibit the ROS generation induced by GOX, which indicated that CsA had no antioxidant function. Moreover, GOX induced typical apoptosis characteristics including, mitochondrial dysfunction, accumulation of Bax and release of cytochrome C in mitochondria, accompanied with activation of caspase-9 and caspase-3. These processions were suppressed after pretreatment with CsA and pifithrin-MU (PFT-MU, a specific inhibitor of p53 mitochondrial translocation). In vivo, CsA was able to attenuate p53 mitochondrial distribution and protect mice liver against from GOX mediated apoptotic cell death. Taken together, these suggested that CsA could suppress ROS-mediated p53 mitochondrial distribution and cell apoptosis depended on its inhibition effect to mitochondrial permeability transition. It might be used to rescue the hepatic cell apoptosis in the patients with acute liver injury. PMID- 26884718 TI - Diabetes Induced Changes in Podocyte Morphology and Gene Expression Evaluated Using GFP Transgenic Podocytes. AB - The effect of diabetes in vivo has not been examined on isolated podocytes. To achieve this, GFP was expressed constitutively in podocytes of PGFP transgenic mice which were bred to OVE mice to produce diabetic OVE-GFP mice. Viewing GFP fluorescence, foot processes of OVE-GFP podocytes were visually and measurably effaced, which did not occur with less severe STZ diabetes. Over 300,000 podocytes were purified from each PGFP mouse but only 49,000 podocytes per diabetic OVE-GFP mouse. The low yield from OVE-GFP mice appeared to be due to more fragile state of most OVE-GFP diabetic podocytes which did not survive the isolation process. Diabetic podocytes that were isolated had high levels of the lipid peroxidation product 4-HNE and they were more sensitive to death due to oxidative stress. Gene array analysis of OVE-GFP podocytes showed strong diabetes induction of genes involved in inflammation. Four CXC chemokines were induced at least 3-fold and the chemokine CXCL1 was shown for the first time to be specifically induced in podocytes by OVE, dbdb and STZ diabetes. PMID- 26884719 TI - Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver. AB - Hepatic triglycerides production and adipose lipolysis are pivotal for long-term stress (LTS) or hyperglucocorticoidemia-induced insulin resistance. 5 hydroxytryptamine (5-HT) has been demonstrated to induce hepatic lipid metabolic abnormality by activating mammalian target of rapamycin (mTOR). In present study, we explored whether 5-HT is involved in LTS effects in liver using restraint stress-exposed rats and cultured primary rat hepatocytes and HepG2 cells. LTS with hyperglucocorticoidemia induced hepatic 5-HT synthetic increase with tryptophan hydroxylase 1 (Tph1) up-regulation, and 5-HT2 receptor (5-HT2R, including 5-HT2A, 2B receptor) up-regulation in liver and visceral adipose, as well as hepatic mTOR activation with triglycerides and VLDL overproduction with steatosis, and visceral adipose lipolytic increase with high blood free fatty acids (FFAs) level. 5-HT exposure exhibited LTS-like effects in both tissues, and both LTS and 5-HT effects could be abolished significantly by blocking 5-HT2R. In HepG2 cells dexamethasone or palmitate-induced mTOR activation with triglycerides and VLDL overproduction were accompanied by up-regulations of 5-HT synthesis and 5-HT2R, which were significantly abolished by gene silencing Tph1 or 5-HT2R and were almost fully abolished by co-silencing of both, especially on VLDL overproduction. Chemical inhibition of Tph1 or/and 5-HT2R in both hepatocytes exhibited similar abolishment with genetic inhibition on dexamethason-induced effects. 5-HT-stimulated effects in both hepatocytes were fully abolished by blocking 5-HT2R, while 5-HT itself also up-regulated 5-HT2R. In conclusion, up regulated hepatic 5-HT synthesis and 5-HT2R induced by both glucocorticoid and FFAs are crucial for LTS-induced hepatic steatosis with VLDL overproduction, while 5-HT by acting on 5-HT2R mediates mTOR activation in liver. PMID- 26884720 TI - Selective Regulation of MAPK Signaling Mediates RANKL-dependent Osteoclast Differentiation. AB - Different stimuli often activate the same intracellular signaling molecules but trigger distinct cell responses. We explored whether or not MAPK signaling induced by macrophage colony-stimulating factor (M-CSF), which is responsible for osteoclast proliferation, differs from that induced by receptor activator of NF kappaB ligand (RANKL), which is essential for inducing osteoclast differentiation. The activation of MAPKs by M-CSF or RANKL differed in terms of the extent and duration of ERK, p38, and JNK phosphorylation as well as the isoform specificity of JNK phosphorylation. In particular, RANKL induced a second wave of MAPK activation coincident with the onset of osteoclast differentiation, whereas M-CSF triggered only a monophasic response. M-CSF was also able to trigger a full MAPK response on restimulation of cells earlier than was RANKL, representing that MAPK resensitization by M-CSF differs from that by RANKL. Furthermore, the adapter protein TRAF6 recruitment to the cytoplasmic tail of RANK in a submembrane compartment is specifically required for RANKL-induced activation of p38 MAPK, expression of osteoclastogenic transcription factors, and osteoclast differentiation, indicating that the switch from proliferation to differentiation in osteoclast precursors is dependent on p38 activation via the RANKL-RANK-TRAF6 axis. Our results suggest that selective control of MAPK signaling induced by M-CSF and by RANKL mediates the proliferation versus differentiation decision in osteoclast precursors. PMID- 26884721 TI - A Group of Novel Serum Diagnostic Biomarkers for Multidrug-Resistant Tuberculosis by iTRAQ-2D LC-MS/MS and Solexa Sequencing. AB - The epidemic of pulmonary tuberculosis (TB), especially multidrug-resistance tuberculosis (MDR-TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) and Solexa sequencing among MDR-TB patients, drug-sensitive tuberculosis (DS-TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P<0.05) were identified in the MDR-TB patients compared to both DS-TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen-1 (KNG1), miR-4433b-5p, miR-424-5p, and miR-199b-5p were found among MDR-TB patients, DS-TB patients and healthy controls (P<0.05) by enzyme-linked immunosorbent assay (ELISA) and SYBR green qRT-PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between miR-199b-5p and KNG1 (r=-0.232, P=0.017). Moreover, we established the MDR-TB diagnostic model based on five biomarkers (CD44, KNG1, miR-4433b-5p, miR-424-5p, and miR-199b-5p). Our study proposes potential biomarkers for MDR-TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR-TB. PMID- 26884722 TI - Wheat Transcription Factor TaAREB3 Participates in Drought and Freezing Tolerances in Arabidopsis. AB - AREB (ABA response element binding) proteins in plants play direct regulatory roles in response to multiple stresses, but their functions in wheat (Triticum aestivum L.) are not clear. In the present study, TaAREB3, a new member of the AREB transcription factor family, was isolated from wheat. Sequence analysis showed that the TaAREB3 protein is composed of three parts, a conserved N terminal, a variable M region, and a conserved C-terminal with a bZIP domain. It belongs to the group A subfamily of bZIP transcription factors. TaAREB3 was constitutively expressed in stems, leaves, florets, anthers, pistils, seeds, and most highly, in roots. TaAREB3 gene expression was induced with abscisic acid (ABA) and low temperature stress, and its protein was localized in the nucleus when transiently expressed in tobacco epidermal cells and stably expressed in transgenic Arabidopsis. TaAREB3 protein has transcriptional activation activity, and can bind to the ABRE cis-element in vitro. Overexpression of TaAREB3 in Arabidopsis not only enhanced ABA sensitivity, but also strengthened drought and freezing tolerances. TaAREB3 also activated RD29A, RD29B, COR15A, and COR47 by binding to their promoter regions in transgenic Arabidopsis. These results demonstrated that TaAREB3 plays an important role in drought and freezing tolerances in Arabidopsis. PMID- 26884723 TI - The Vertical Distribution of Sediment Archaeal Community in the "Black Bloom" Disturbing Zhushan Bay of Lake Taihu. AB - Using the Illumina sequencing technology, we investigated the vertical distribution of archaeal community in the sediment of Zhushan Bay of Lake Taihu, where the black bloom frequently occurred in summer. Overall, the Miscellaneous Crenarchaeotal Group (MCG), Deep Sea Hydrothermal Vent Group 6 (DHVEG-6), and Methanobacterium dominated the archaeal community. However, we observed significant difference in composition of archaeal community among different depths of the sediment. DHVEG-6 dominated in the surface layer (0-3 cm) sediment. Methanobacterium was the dominating archaeal taxa in the L2 (3-6 cm) and L3 (6 10) sediment. MCG was most abundant in the L4 (10-15 cm) and L5 (15-20 cm) sediment. Besides, DHVEG-6 was significantly affected by the concentration of total phosphorus (TP). And loss on ignition (LOI) was an important environmental factor for Methanobacterium. As the typical archaeal taxa in the surface layer sediment, DHVEG-6 and Methanobacterium might be more adapted to abundant substrate supply from cyanobacterial blooms and take active part in the biomass transformation. We propose that DHVEG-6 and Methanobacterium could be the key archaeal taxa correlated with the "black bloom" formation in Zhushan Bay. PMID- 26884724 TI - ELF5 and DOK7 regulation in anti-estrogen treated cells and tumors. AB - BACKGROUND: Most women with primary breast cancers that express estrogen receptor alpha (ER or ESR1) are treated with endocrine therapies including the anti estrogen tamoxifen, but resistance to these anti-endocrine therapies often develops. This study characterizes the expression of hormone receptors, and the mRNA and DNA methylation levels of docking protein 7 (DOK7), and E74-like factor 5 (ELF5), in 21 novel tamoxifen-resistant cell lines and extends the findings to primary and recurrent human breast tumors. METHODS: Twenty-one tamoxifen-selected cell lines were developed through cloning by limiting dilution of an MCF-7 cell culture treated with 1 MUM tamoxifen for 6 months. The parent (MCF-7) and tamoxifen-selected cell lines were characterized for protein expression of ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) using immunohistochemistry (IHC). The mRNA levels of ER, DOK7, and ELF5 were assessed using quantitative RT-PCR. Promoter methylation levels of DOK7 and ELF5 were determined by pyrosequencing of bisulfite-modified DNA. The relationship between hormone receptor status and promoter methylation of DOK7 and ELF5 was further examined using available methylation array data (Illumina HM450) from a set of paired primary and second breast tumors from 24 women. RESULTS: All 21 of the novel tamoxifen-selected cell lines are ER-positive, and HER2-negative, and 18 of the cell lines are PR-negative while the MCF-7 cells were scored as ER positive, modestly PR-positive and HER2 negative. Expression of DOK7 and ELF5 is significantly up-regulated in half of the tamoxifen-selected cell lines as compared to the parental MCF-7. In contrast, the previously established ER negative TMX2-28 cell line has decreased expression of both DOK7 and ELF5 and increased DNA methylation in the transcriptional start site region of these genes. ELF5 methylation was lower in second versus primary tumors in women who received anti-estrogen treatment, in PR-negative versus PR-positive tumors, and in the subset of PR-positive first tumors from the group of women who had second PR-negative tumors as compared to those who had second PR-positive tumors. CONCLUSIONS: The distinct ELF5 methylation of PR-positive primary tumors from women who had a PR-negative recurrence indicates the possibility of stratification of women for tailored treatment in the early stages of disease. PMID- 26884725 TI - Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth. AB - BACKGROUND: The most common genetic changes identified in human NSCLC are Kras mutations (10-30 %) and p53 mutation or loss (50-70 %). Moreover, NSCLC with mutations in Kras and p53 poorly respond to current therapies, so we are trying to find a new target for the treatment strategies. METHODS: Flow cytometry, crystal violet staining and immunoblotting were used to assess cell cycle arrest, proliferation and apoptosis in lung cancer cell lines after 2-DG treatment and lentivirus infection by shRNA knock down. IHC and western blotting were carried for NSG xenograft model with 2-DG treatment and lentivirus infection by shRNA knock down. RESULTS: Knocking down Kras down-regulated the glycolytic enzyme hexokinase II (HK2) in KP2 (mouse lung cancer cell line with Kras mutation and p53 deletion) and H23 (human lung cancer cell line with Kras mutation and p53 mutation) cell lines. Genetic studies revealed that HK2 was required for the human and mouse lung cancer cell growth in vitro and in vivo. Our pharmacological studies confirmed that 2-DG, an inhibitor of HK2, inhibited human and mouse lung cancer cell growth through inducing cell apoptosis and autophagy. CONCLUSIONS: HK2 is a promising treatment target for NSCLC with Kras activating and p53 function loss. PMID- 26884727 TI - A new start for 'Intestinal Research' as an official journal of AOCC. PMID- 26884726 TI - Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells. AB - BACKGROUND: The use of the dietary polyphenols as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention of scientists and clinicians as a plausible approach for overcoming the limitations of chemotherapy (e.g. drug resistance and cytotoxicity). The aim of this study was to investigate whether a naturally occurring diet-based flavonoid, fisetin, at physiologically attainable concentrations, could act synergistically with clinically achievable doses of paclitaxel to produce growth inhibitory and/or pro-death effects on A549 non-small cell lung cancer cells, and if it does, what mechanisms might be involved. METHODS: The drug-drug interactions were analyzed based on the combination index method of Chou and Talalay and the data from MTT assays. To provide some insights into the mechanism underlying the synergistic action of fisetin and paclitaxel, selected morphological, biochemical and molecular parameters were examined, including the morphology of cell nuclei and mitotic spindles, the pattern of LC3-II immunostaining, the formation of autophagic vacuoles at the electron and fluorescence microscopic level, the disruption of cell membrane asymmetry/integrity, cell cycle progression and the expression level of LC3-II, Bax, Bcl-2 and caspase-3 mRNA. RESULTS: Here, we reported the first experimental evidence for the existence of synergism between fisetin and paclitaxel in the in vitro model of non-small cell lung cancer. This synergism was, at least partially, ascribed to the induction of mitotic catastrophe. The switch from the cytoprotective autophagy to the autophagic cell death was also implicated in the mechanism of the synergistic action of fisetin and paclitaxel in the A549 cells. In addition, we revealed that the synergism between fisetin and paclitaxel was cell line-specific as well as that fisetin synergizes with arsenic trioxide, but not with mitoxantrone and methotrexate in the A549 cells. CONCLUSIONS: Our results provide rationale for further testing of fisetin in the combination with paclitaxel or arsenic trioxide to obtain detailed insights into the mechanism of their synergistic action as well as to evaluate their toxicity towards normal cells in an animal model in vivo. We conclude that this study is potentially interesting for the development of novel chemotherapeutic approach to non-small cell lung cancer. PMID- 26884728 TI - Are there interregional differences in the epidemiology and clinical characteristics of Crohn's disease in the Asia-Pacific region? PMID- 26884729 TI - Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin? AB - Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted. PMID- 26884730 TI - Current status of biosimilars in the treatment of inflammatory bowel diseases. AB - Introduction of biological therapies have led to dramatic changes in the management of debilitating immune-mediated inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease. However, the long term use of these agents may be very expensive, placing a significant burden on National Healthcare Systems. The development of first biosimilar to infliximab, CT-P13 (Remsima; Celltrion Inc., Incheon, Korea and Inflextra; Hospiral, Lake Forest, Illinois, USA) has become another way to decrease the medical care cost and increase patient treatment option, but, actual equivalence of efficacy and safety of CT-P13 was investigated in rheumatic diseases only. The extrapolation of outcome from rheumatic trials to IBD and the interchangeability of CT-P13 with infliximab have come to be a matter of concern. Two recent retrospective studies reported the similarity of CT-P13 in terms of efficacy and safety. Infliximab biosimilars may be promising new treatment options for IBD patients, however, well-designed, prospective randomized non-inferiority trials should be needed to confidently integrate infliximab biosimilars into IBD treatment. PMID- 26884731 TI - Current status and future perspectives of capsule endoscopy. AB - Small bowel capsule endoscopy (CE) was first introduced 15 years ago, and a large amount of literature has since been produced, focused on its indication, diagnostic yields, and safety. Guidelines that have made CE the primary diagnostic tool for small bowel disease have been created. Since its initial use in the small bowel, CE has been used for the esophagus, stomach, and colon. The primary indications for small bowel CE are obscure gastrointestinal bleeding, unexplained iron deficiency anemia, suspected Crohn's disease, small bowel tumors, nonsteroidal anti-inflammatory drug enteropathy, portal hypertensive enteropathy, celiac disease, etc. Colon CE provides an alternative to conventional colonoscopy, with possible use in colorectal cancer screening. Guidelines for optimal bowel preparation of CE have been suggested. The main challenges in CE are the development of new devices with the ability to provide therapy, air inflation for better visualization of the small bowel, biopsy sampling systems attached to the capsule, and the possibility of guiding and moving the capsule by an external motion controller. We review the current status and future directions of CE, and address all aspects of clinical practice, including the role of CE and long-term clinical outcomes. PMID- 26884732 TI - Clinical features of Crohn's disease in Korean patients residing in Busan and Gyeongnam. AB - BACKGROUND/AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disease that presents with variable features and repeated disease aggravation. The incidence of CD is increasing in Korea. We evaluated the clinical features of CD in a study population in Busan and Gyeongnam, Korea. METHODS: A hospital-based analysis included 619 patients diagnosed with CD between March 1986 and February 2013 from seven tertiary care hospitals in Busan and Gyeongnam. Individual case records were reviewed with regard to age at diagnosis, sex, disease location, disease behavior, and medical and surgical treatments received during the follow up period. RESULTS: The cumulative frequency of patients diagnosed with CD revealed a continued increase in the number of cases reported yearly. The male-to female ratio was 2.5:1 and the median age at diagnosis was 24 years. At diagnosis, 114 (18.4%) had isolated small bowel disease, 144 (23.3%) had isolated colonic disease, and 358 patients (57.8%) presented with disease in the small bowel and colon. The number of patients presenting with stricturing or penetrating disease behavior was 291 (47%) at the final evaluation. In total, 111 (17.9%) patients underwent intestinal resections. CONCLUSIONS: A continued increase in the number of patients diagnosed with CD was found in Busan and Gyeongnam as observed in other regions. We report results similar to that of other Korean studies in terms of sex distribution, age, and location of disease. PMID- 26884733 TI - The predictive variable regarding relapse in patients with ulcerative colitis after achieving endoscopic mucosal healing. AB - BACKGROUND/AIMS: Mucosal healing (MH) is a proposed therapeutic goal for patients with ulcerative colitis (UC). Whether MH is the final goal for UC, however, remains under debate. Therefore, to elucidate clinical variables predicting relapse after MH in UC could be useful for establishing further therapeutic strategy. The aim of this study is to evaluate the predictive variables for relapse in UC-patients after achieving MH. METHODS: From April 2010 to February 2015, 298 UC-patients treated at Kitano Hospital were retrospectively analyzed. MH was defined as Mayo endoscopic subscore of 0 or 1. The cumulative relapse free rate after achieving MH was evaluated. Predictive variables for relapse in UC patients were assessed by Cox regression analysis. RESULTS: Of 298 UC-patients, 88 (29.5%) achieved MH. Of the 88 UC patients who achieved MH, 21 (23.9%) experienced UC-relapse. Based on Kaplan-Meier analysis, the cumulative relapse free rate at 1, 3, and 5 years after achieving MH was 87.9%, 70.2%, and 63.8%, respectively. The cumulative relapse free rate tended to be higher in the Mayo-0 group (76.9%) than in the Mayo-1 group (54.1%) at 5 years, although the difference was not statistically significant (P=0.313). Cox regression analysis indicated that the use of an immunomodulator was a predictive variable for relapse in UC-patients after achieving MH (P=0.035). CONCLUSIONS: Our data demonstrated that the prognosis of UC patients after achieving endoscopic MH could be based on UC refractoriness requiring an immunomodulator. PMID- 26884734 TI - The prevalence and clinical characteristics of anemia in Korean patients with inflammatory bowel disease. AB - BACKGROUND/AIMS: Quality of life is closely related to anemia in patients with inflammatory bowel disease (IBD). Several studies have reported on anemia in patients with IBD in Western countries. This study investigated the prevalence and clinical characteristics of anemia in Korean patients with IBD. METHODS: We reviewed the medical records of 92 patients with ulcerative colitis (UC) and 76 patients with Crohn's disease (CD) who were followed regularly at a single tertiary medical center in Korea between January 2003 and December 2012. Hemoglobin (Hb) thresholds used to define anemia were <13.0 g/dL in men and <12.0 g/dL in women according to the World Health Organization criteria. We chose the lowest Hb level in each year as a representative value because Hb levels changed at each examination and anemia was associated with disease deterioration. The relationship between clinical variables and lowest Hb level was assessed. RESULTS: The prevalence of anemia was 36.3% in patients with UC and 41.6% in patients with CD. Anemia in patients with CD was associated with hospital admission, 5-aminosalicylate (5-ASA) and infliximab treatment in men. Anemia in patients with UC was associated with hospital admission, oral steroid use, thiopurine and infliximab treatment in men. CONCLUSIONS: The prevalence of anemia in Korean patients with IBD was comparable to that of patients in Western countries. Anemia was associated with male patients with CD who were admitted to the hospital and received medications including 5-ASA and infliximab, and men with UC who were admitted to the hospital and received medications including oral steroids, thiopurine and infliximab. PMID- 26884735 TI - Efficacy and safety of two pH-dependent-release mesalamine doses in moderately active ulcerative colitis: a multicenter, randomized, double-blind, parallel group study. AB - BACKGROUND/AIMS: The therapeutic effect of mesalamine is considered to be dose dependent; however, no consensus has been reached regarding the optimal doses for individual patients. This study aimed to provide new insight for dose optimization using two doses of pH-dependent release mesalamine for induction of remission of moderately active ulcerative colitis (UC). METHODS: In a multicenter, double-blind, randomized study, 110 patients with moderately active UC were assigned to two groups after treatment with a constant dose of mesalamine. Fifty-five patients were treated with a pH-dependent release formulation of 3.6 or 4.8 g/day for 8 weeks. The primary endpoint was a decrease in the UC disease activity index (UCDAI) adjusted by covariates. RESULTS: In the full analysis set (n=110), the mean decrease in UCDAI was 3.1 in the 3.6 g/day group and 3.4 in the 4.8 g/day group (P>0.05). In a subgroup analysis, the effectiveness of the 4.8 g/day dose was greater in particular populations, such as those who had been previously treated with a lower dose of mesalamine and those with more severe disease. The safety was comparable between the two groups. CONCLUSIONS: The results suggest that treatment with pH-dependent release mesalamine at either 3.6 or 4.8 g/day was effective and safe for the induction of remission in patients with moderately active UC. However, the patients receiving mesalamine at 2.4 g/day but in whom the therapeutic effect is not sufficient and having more severe symptoms (UCDAI 9-10), benefit from higher doses of mesalamine compared to others. PMID- 26884737 TI - The role of capsule endoscopy in etiological diagnosis and management of obscure gastrointestinal bleeding. AB - BACKGROUND/AIMS: To investigate the various etiologies, yields, and effects of capsule endoscopy (CE) on management and complications, along with follow up of patients with obscure gastrointestinal (GI) bleeding. METHODS: The study group of patients included those having obscure, overt, or occult GI bleeding. The findings were categorized as (A) obvious/definitive, (B) equivocal, or (C) negative. Any significant alteration in patient management post CE in the form of drug or surgical intervention was noted. RESULTS: Total patients included in the study were 68 (48 males and 20 females). The ratio of male:female was 2.4:1. The age ranged between 16 years to 77 years. Mean age for males was 62+/-14 years, for females 58+/-16 years. The total yield of CE with definitive lesions was in 44/68 (65.0%) of patients. In descending order (A) angiodysplasia 16/68 (23.53%), (B) Crohn's disease 10/68 (14.70%), (C) non-steroidal anti-inflammatory drug enteropathy 8/68 (11.76%), (D) small bowel ulcers 4/68 (5.88%), (E) jejunal and ileal polyps 2/68 (2.94%), (F) intestinal lymphangiectasis 2/68 (2.94%), and (G) ileal hemangiomas 2/68 (2.94%) were followed. Equivocal findings 12/68 (17.65%) and negative study 12/68 (17.65%) was found. Complications in the form of capsule retention in the distal ileum were noted in 2/68 (2.94%) subjects. Statistically, there was a higher probability of finding the etiology if the CE was done during an episode of bleeding. CONCLUSIONS: CE plays an important role in diagnosing etiologies of obscure GI bleeding. Its role in influencing the management outcome is vital. PMID- 26884738 TI - Spectrum of chronic small bowel diarrhea with malabsorption in Indian subcontinent: is the trend really changing? AB - BACKGROUND/AIMS: This study aimed to document the recent etiological spectrum of chronic diarrhea with malabsorption and also to compare features that differentiate tropical sprue from parasitic infections, the two most common etiologies of malabsorption in the tropics. METHODS: We analyzed 203 consecutive patients with malabsorption. The etiological spectrum and factors that differentiated tropical sprue from parasitic infections were analyzed. RESULTS: The most common etiology was tropical sprue (n=98, 48.3%) followed by parasitic infections (n=25, 12.3%) and tuberculosis (n=22, 10.8%). Other causes were immunodeficiency (n=15, 7.3%; 12 with human immunodeficiency virus and 3 with hypogammaglobulinemia), celiac disease (n=11, 5.4%), Crohn's disease (n=11, 5.4%), small intestinal bacterial overgrowth (n=11, 5.4%), hyperthyroidism (n=4, 1.9%), diabetic diarrhea (n=4, 1.9%), systemic lupus erythematosus (n=3, 1.4%), metastatic carcinoid (n=1, 0.5%) and Burkitt's lymphoma (n=1, 0.5%). On multivariate analysis, features that best differentiated tropical sprue from parasitic infections were larger stool volume (P=0.009), severe weight loss (P=0.02), knuckle hyperpigmentation (P=0.008), low serum B12 levels (P=0.05), high mean corpuscular volume (P=0.003), reduced height or scalloping of the duodenal folds on endoscopy (P=0.003) and villous atrophy on histology (P=0.04). Presence of upper gastrointestinal (GI) symptoms like bloating, nausea and vomiting predicted parasitic infections (P=0.01). CONCLUSIONS: Tropical sprue and parasitic infections still dominate the spectrum of malabsorption in India. Severe symptoms and florid malabsorption indicate tropical sprue while the presence of upper GI symptoms indicates parasitic infections. PMID- 26884736 TI - Gastric lesions in patients with Crohn's disease in Korea: a multicenter study. AB - BACKGROUND/AIMS: Gastric pathology and Helicobacter pylori (H. pylori) infection among Asian patients with Crohn's disease (CD) are still unclear. We evaluated gastric histologic features and frequency of H. pylori infection in Korean patients with CD. METHODS: Among 492 patients with CD receiving upper gastrointestinal (GI) endoscopic evaluation in 19 Korean hospitals, we evaluated the endoscopic findings and gastric histopathologic features of 47 patients for our study. Histopathologic classification was performed using gastric biopsy tissues, and H. pylori infection was determined using the rapid urease test and histology. RESULTS: There were 36 men (76.6%), and the median age of patients at the time of upper GI endoscopy was 23.8 years (range, 14.2-60.5). For CD phenotype, ileocolonic disease was observed in 38 patients (80.9%), and non stricturing, non-penetrating disease in 31 patients (66.0%). Twenty-eight patients (59.6%) complained of upper GI symptoms. Erosive gastritis was the most common gross gastric feature (66.0%). Histopathologically, H. pylori-negative chronic active gastritis (38.3%) was the most frequent finding. H. pylori testing was positive in 11 patients (23.4%), and gastric noncaseating granulomata were detected in 4 patients (8.5%). Gastric noncaseating granuloma showed a statistically significant association with perianal abscess/fistula (P=0.0496). CONCLUSIONS: H. pylori-negative chronic active gastritis appears to be frequent among Korean patients with CD. The frequency of H. pylori infection was comparable with previous studies. An association with perianal complications suggests a prognostic value for gastric noncaseating granuloma in patients with CD. PMID- 26884739 TI - Refractory pseudomembranous colitis that was treated successfully with colonoscopic fecal microbial transplantation. AB - Pseudomembranous colitis (PMC) is a nosocomial and opportunistic infection caused by Clostridium difficile. PMC is related to the use of antibiotics leading to intestinal dysbiosis and an overgrowth of C. difficile. Metronidazole or vancomycin is considered to be the standard therapy for the management of PMC. However, PMC has a 15%-30% recurrence rate and can be refractory to standard treatments, resulting in morbidity and mortality. Here we describe a patient who experienced refractory PMC who was treated with fecal microbiota transplantation. A 69-year-old woman was admitted to the hospital with consistent abdominal pain and diarrhea, which had been present for 5 months. She was diagnosed with PMC by colonoscopy and tested positive for C. difficile toxin. Even though she took metronidazole for 10 days, followed by vancomycin for 4 weeks, her symptoms did not improve. Because of her recurrent and refractory symptoms, we decided to perform fecal microbiota transplantation. Fifty grams of fresh feces from a donor were obtained on the day of the procedure, mixed with 500 mL of normal saline, and then filtered. The filtered solution was administered to the patient's colon using a colonoscope. After the procedure, her symptoms rapidly improved and a follow-up colonoscopy showed that the PMC had resolved without recurrence. PMID- 26884740 TI - Ischemic enteritis with intestinal stenosis. AB - A 75-year-old man was admitted to our hospital with sudden onset of vomiting and abdominal distension. The patient was taking medication for arrhythmia. Computed tomography showed stenosis of the ileum and a small bowel dilatation on the oral side from the region of stenosis. A transnasal ileus tube was placed. Enteroclysis using contrast medium revealed an approximately 6-cm afferent tubular stenosis 10 cm from the terminal ileum and thumbprinting in the proximal bowel. Transanal double-balloon enteroscopy showed a circumferential shallow ulcer with a smooth margin and edema of the surrounding mucosa. The stenosis was so extensive that we could not perform endoscopic balloon dilation therapy. During hospitalization, the patient's nutritional status deteriorated. In response, we surgically resected the region of stenosis. Histologic examination revealed disappearance of the mucosal layer and transmural ulceration with marked fibrosis, especially in the submucosal layer. Hemosiderin staining revealed sideroferous cells in the submucosal layers. Based on the pathologic findings, the patient was diagnosed with ischemic enteritis. The patient's postoperative course was uneventful. PMID- 26884741 TI - Cerebral venous thrombosis in a patient with Crohn's disease. AB - Patients with inflammatory bowel disease (IBD) have an elevated risk of venous thromboembolism compared with the general population. The most common sites of venous thromboembolism in IBD patients are the deep veins of the legs, the pulmonary system, and portal and mesenteric veins. However, cerebral venous thrombosis is rarely associated with IBD. This report describes a case of cerebral venous thrombosis in a patient with Crohn's disease. A 17-year-old girl, diagnosed 4 years earlier with Crohn's disease, presented with headache and vomiting. Magnetic resonance imaging of the brain with venography showed venous thrombosis in the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. The patient immediately started anticoagulation therapy with intravenous heparin infusion followed by daily oral rivaroxaban 10 mg. Follow-up imaging after 2 weeks showed resolution of the thrombosis, with recanalization of the cortical veins, superior sagittal sinus, right transverse sinus, and right internal jugular vein. She continued rivaroxaban therapy for 6 months, and remained well, without neurologic sequelae. A high level of concern for cerebral venous thrombosis may be important when treating active IBD patients, because anticoagulation treatment can prevent fatal complications. PMID- 26884742 TI - Cutaneous lesions in colorectal carcinoma: a rare presentation. PMID- 26884743 TI - A large symptomatic jejunal subepithelial tumor treated with endoloop-assisted polypectomy using spiral enteroscopy. PMID- 26884744 TI - Anticancer properties of phospholipase A2 from Daboia siamensis venom on human skin melanoma cells. AB - BACKGROUND: Phospholipase A2 (PLA2) is a major component of the Daboia siamensis venom, which is able to hydrolyse the membrane of various cells. For this reason, the activity of PLA2 was investigated regarding its pharmaceutical properties. This study was conducted to explore the pharmacological properties of a PLA2 from Daboia siamensis (dssPLA2) venom on human skin melanoma cell line (SK-MEL-28). METHODS: dssPLA2 was isolated by ion exchange and gel filtration columns. Various concentrations of dssPLA2 were investigated for cytotoxic activity and inhibition of migration on SK-MEL-28 cells. Cell death analysis, mRNA expression levels of Notch I-III and BRAF V600E genes were also determined. RESULTS: dssPLA2 exhibited cytotoxicity on SK-MEL-28 for 24 and 72 h as compared with untreated cells. However, it had no toxic effects on CCD-1064sk cells under the same conditions. dssPLA2 (0.25 and 0.5 MUg/mL) induced 17.16 and 30.60 % of apoptosis, while activated 6.53 and 7.05 % of necrotic cells. dssPLA2 at 0.25, 0.5, 1 and 2 MUg/mL could inhibit migration on SK-MEL-28 cells for 24 h by 31.06, 41.66, 50 and 68.75 %, respectively. The action of dssPLA2 significantly reduced the levels of Notch I and BRAF V600E genes expression on SK-MEL-28 cells compared with untreated cells at 72 h. CONCLUSIONS: This study indicates that dssPLA2 had potential effects of apoptosis, necrosis, cytotoxicity and inhibition of migration on SK MEL-28 cells. dssPLA2 could possibly be a selective agent that targets cancer cells without affecting normal cells. PMID- 26884745 TI - Layout Design of Human-Machine Interaction Interface of Cabin Based on Cognitive Ergonomics and GA-ACA. AB - In order to consider the psychological cognitive characteristics affecting operating comfort and realize the automatic layout design, cognitive ergonomics and GA-ACA (genetic algorithm and ant colony algorithm) were introduced into the layout design of human-machine interaction interface. First, from the perspective of cognitive psychology, according to the information processing process, the cognitive model of human-machine interaction interface was established. Then, the human cognitive characteristics were analyzed, and the layout principles of human machine interaction interface were summarized as the constraints in layout design. Again, the expression form of fitness function, pheromone, and heuristic information for the layout optimization of cabin was studied. The layout design model of human-machine interaction interface was established based on GA-ACA. At last, a layout design system was developed based on this model. For validation, the human-machine interaction interface layout design of drilling rig control room was taken as an example, and the optimization result showed the feasibility and effectiveness of the proposed method. PMID- 26884746 TI - How Many Is Enough? Effect of Sample Size in Inter-Subject Correlation Analysis of fMRI. AB - Inter-subject correlation (ISC) is a widely used method for analyzing functional magnetic resonance imaging (fMRI) data acquired during naturalistic stimuli. A challenge in ISC analysis is to define the required sample size in the way that the results are reliable. We studied the effect of the sample size on the reliability of ISC analysis and additionally addressed the following question: How many subjects are needed for the ISC statistics to converge to the ISC statistics obtained using a large sample? The study was realized using a large block design data set of 130 subjects. We performed a split-half resampling based analysis repeatedly sampling two nonoverlapping subsets of 10-65 subjects and comparing the ISC maps between the independent subject sets. Our findings suggested that with 20 subjects, on average, the ISC statistics had converged close to a large sample ISC statistic with 130 subjects. However, the split-half reliability of unthresholded and thresholded ISC maps improved notably when the number of subjects was increased from 20 to 30 or more. PMID- 26884747 TI - Motivation Classification and Grade Prediction for MOOCs Learners. AB - While MOOCs offer educational data on a new scale, many educators find great potential of the big data including detailed activity records of every learner. A learner's behavior such as if a learner will drop out from the course can be predicted. How to provide an effective, economical, and scalable method to detect cheating on tests such as surrogate exam-taker is a challenging problem. In this paper, we present a grade predicting method that uses student activity features to predict whether a learner may get a certification if he/she takes a test. The method consists of two-step classifications: motivation classification (MC) and grade classification (GC). The MC divides all learners into three groups including certification earning, video watching, and course sampling. The GC then predicts a certification earning learner may or may not obtain a certification. Our experiment shows that the proposed method can fit the classification model at a fine scale and it is possible to find a surrogate exam-taker. PMID- 26884748 TI - An Effective Color Quantization Method Using Octree-Based Self-Organizing Maps. AB - Color quantization is an essential technique in color image processing, which has been continuously researched. It is often used, in particular, as preprocessing for many applications. Self-Organizing Map (SOM) color quantization is one of the most effective methods. However, it is inefficient for obtaining accurate results when it performs quantization with too few colors. In this paper, we present a more effective color quantization algorithm that reduces the number of colors to a small number by using octree quantization. This generates more natural results with less difference from the original image. The proposed method is evaluated by comparing it with well-known quantization methods. The experimental results show that the proposed method is more effective than other methods when using a small number of colors to quantize the colors. Also, it takes only 71.73% of the processing time of the conventional SOM method. PMID- 26884749 TI - Retreatment Predictions in Odontology by means of CBR Systems. AB - The field of odontology requires an appropriate adjustment of treatments according to the circumstances of each patient. A follow-up treatment for a patient experiencing problems from a previous procedure such as endodontic therapy, for example, may not necessarily preclude the possibility of extraction. It is therefore necessary to investigate new solutions aimed at analyzing data and, with regard to the given values, determine whether dental retreatment is required. In this work, we present a decision support system which applies the case-based reasoning (CBR) paradigm, specifically designed to predict the practicality of performing or not performing a retreatment. Thus, the system uses previous experiences to provide new predictions, which is completely innovative in the field of odontology. The proposed prediction technique includes an innovative combination of methods that minimizes false negatives to the greatest possible extent. False negatives refer to a prediction favoring a retreatment when in fact it would be ineffective. The combination of methods is performed by applying an optimization problem to reduce incorrect classifications and takes into account different parameters, such as precision, recall, and statistical probabilities. The proposed system was tested in a real environment and the results obtained are promising. PMID- 26884750 TI - Learning-Based Visual Saliency Model for Detecting Diabetic Macular Edema in Retinal Image. AB - This paper brings forth a learning-based visual saliency model method for detecting diagnostic diabetic macular edema (DME) regions of interest (RoIs) in retinal image. The method introduces the cognitive process of visual selection of relevant regions that arises during an ophthalmologist's image examination. To record the process, we collected eye-tracking data of 10 ophthalmologists on 100 images and used this database as training and testing examples. Based on analysis, two properties (Feature Property and Position Property) can be derived and combined by a simple intersection operation to obtain a saliency map. The Feature Property is implemented by support vector machine (SVM) technique using the diagnosis as supervisor; Position Property is implemented by statistical analysis of training samples. This technique is able to learn the preferences of ophthalmologist visual behavior while simultaneously considering feature uniqueness. The method was evaluated using three popular saliency model evaluation scores (AUC, EMD, and SS) and three quality measurements (classical sensitivity, specificity, and Youden's J statistic). The proposed method outperforms 8 state-of-the-art saliency models and 3 salient region detection approaches devised for natural images. Furthermore, our model successfully detects the DME RoIs in retinal image without sophisticated image processing such as region segmentation. PMID- 26884751 TI - Constipation and Laxative Use among Nursing Home Patients: Prevalence and Associations Derived from the Residents Assessment Instrument for Long-Term Care Facilities (interRAI LTCF). AB - Introduction. Constipation is a common, bothersome, and potentially dangerous condition among nursing home (NH) patients. Between 50 and 74% of NH patients use laxatives. Objective. To study prevalence and associations of laxative use and constipation using the comprehensive Norwegian version of the Resident Assessment Instrument for Long-Term Care Facilities. Methods. Cross-sectional study. Patients from 20 NH units were included. Logistic regression was used to analyze the results. Data collected in NHs might be clustered. Consequently, the multivariable models were tested against a mixed effects regression model to investigate variance both on the level of patients and on the level of NH units. Results. In all, 261 patients were included. The prevalence of constipation was 23.4%, and 67.1% used laxatives regularly. Balance problems, urinary incontinence, hypothyroidism, and Parkinson's disease were associated with constipation. Reduced ability to communicate and number of drugs were associated with laxative use. Antidementia-drugs and being involved in activities 1/3 to 2/3 of daytime were protective factors for laxative use. Mixed effects analyses identified variance on the level of NH units as nonsignificant. Conclusion. Constipation and laxative use are common. Variance is mainly explained by different patient characteristics/health deficiencies. Hence, patients might benefit from individualized care to compensate for deficiencies. PMID- 26884752 TI - Single Nucleotide Polymorphisms as Prognostic and Predictive Factors of Adjuvant Chemotherapy in Colorectal Cancer of Stages I and II. AB - Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant. PMID- 26884753 TI - Early Gastric Cancer: Current Advances of Endoscopic Diagnosis and Treatment. AB - Endoscopy is a major method for early gastric cancer screening because of its high detection rate, but its diagnostic accuracy depends heavily on the availability of endoscopic instruments. Many novel endoscopic techniques have been shown to increase the diagnostic yield of early gastric cancer. With the improved detection rate of EGC, the endoscopic treatment has become widespread due to advances in the instruments available and endoscopist's experience. The aim of this review is to summarize frequently-used endoscopic diagnosis and treatment in early gastric cancer (EGC). PMID- 26884755 TI - Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves. AB - In the present study, we evaluated anti-Parkinson's activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6 OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson's disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly (p < 0.001) found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress. PMID- 26884757 TI - Tablet PC Enabled Body Sensor System for Rural Telehealth Applications. AB - Telehealth systems benefit from the rapid growth of mobile communication technology for measuring physiological signals. Development and validation of a tablet PC enabled noninvasive body sensor system for rural telehealth application are discussed in this paper. This system includes real time continuous collection of physiological parameters (blood pressure, pulse rate, and temperature) and fall detection of a patient with the help of a body sensor unit and wireless transmission of the acquired information to a tablet PC handled by the medical staff in a Primary Health Center (PHC). Abnormal conditions are automatically identified and alert messages are given to the medical officer in real time. Clinical validation is performed in a real environment and found to be successful. Bland-Altman analysis is carried out to validate the wrist blood pressure sensor used. The system works well for all measurements. PMID- 26884756 TI - Pathological Characteristics of Primary Bladder Carcinoma Treated at a Tertiary Care Hospital and Changing Demographics of Bladder Cancer in Sri Lanka. AB - Objectives. The aim was to compare demographics and pathological features of bladder carcinoma treated in a urology unit with findings of previous studies done in Sri Lanka. Materials and Methods. Data of newly diagnosed patients with bladder cancer in a tertiary referral centre from 2011 to 2014 were analysed. Data on bladder cancers diagnosed from 1993 to 2014 were obtained from previous publications and Sri Lanka Cancer Registry. Results. There were 148 patients and mean age was 65 years. Male to female ratio was 4.1 : 1. Urothelial carcinoma (UC) was found in 89.2% of patients. Muscle invasion was noted in 35% of patients compared to 48.4% two decades ago. In patients with UC, 16.5% were found to have pT1 high grade tumour. It was 5.3% from 1993 to 2000. Pure squamous cell carcinoma was found in 8.1% of patients while primary or de novo carcinoma in situ (not associated with high grade pT1 tumours) was seen in one patient only. Conclusions. The percentage of squamous carcinoma is higher among Sri Lankan patients while primary carcinoma in situ is a rarity. The percentage of muscle invasive disease has decreased while the percentage of pT1 high grade tumours has increased during the last two decades in Sri Lanka. PMID- 26884754 TI - Integrating TRPV1 Receptor Function with Capsaicin Psychophysics. AB - Capsaicin is a naturally occurring vanilloid that causes a hot, pungent sensation in the human oral cavity. This trigeminal stimulus activates TRPV1 receptors and stimulates an influx of cations into sensory cells. TRPV1 receptors function as homotetramers that also respond to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Kinase mediated phosphorylation of TRPV1 leads to increased sensitivity to both chemical and thermal stimuli. In contrast, desensitization occurs via a calcium-dependent mechanism that results in receptor dephosphorylation. Human psychophysical studies have shown that capsaicin is detected at nanomole amounts and causes desensitization in the oral cavity. Psychophysical studies further indicate that desensitization can be temporarily reversed in the oral cavity if stimulation with capsaicin is resumed at short interstimulus intervals. Pretreatment of lingual epithelium with capsaicin modulates the perception of several primary taste qualities. Also, sweet taste stimuli may decrease the intensity of capsaicin perception in the oral cavity. In addition, capsaicin perception and hedonic responses may be modified by diet. Psychophysical studies with capsaicin are consistent with recent findings that have identified TRPV1 channel modulation by phosphorylation and interactions with membrane inositol phospholipids. Future studies will further clarify the importance of capsaicin and its receptor in human health and nutrition. PMID- 26884758 TI - Investigating Therapeutic Potential of Trigonella foenum-graecum L. as Our Defense Mechanism against Several Human Diseases. AB - Current lifestyle, stress, and pollution have dramatically enhanced the progression of several diseases in human. Globally, scientists are looking for therapeutic agents that can either cure or delay the onset of diseases. Medicinal plants from time immemorial have been used frequently in therapeutics. Of many such plants, fenugreek is one of the oldest herbs which have been identified as an important medicinal plant by the researchers around the world. It is potentially beneficial in a number of diseases such as diabetes, hypercholesterolemia, and inflammation and probably in several kinds of cancers. It has industrial applications such as synthesis of steroidal hormones. Its medicinal properties and their role in clinical domain can be attributed to its chemical constituents. The 3 major chemical constituents which have been identified as responsible for principle health effects are galactomannan, 4-OH isoleucine, and steroidal saponin. Numerous experiments have been carried out in vivo and in vitro for beneficial effects of both the crude chemical and of its active constituent. Due to its role in health care, the functional food industry has referred to it as a potential nutraceutical. This paper is about various medicinal benefits of fenugreek and its potential application as therapeutic agent against several diseases. PMID- 26884759 TI - Effects of Thyroid Peroxidase Antibody on Maternal and Neonatal Outcomes in Pregnant Women in an Iodine-Sufficient Area in China. AB - Purposes. To evaluate the effects of thyroid peroxidase antibodies (TPOAb) on maternal and neonatal adverse outcomes in pregnant women. Methods. 208 pregnant women at 24-28 weeks were divided into two groups, TPOAb-positive and TPOAb negative groups. Thyroid function and TPOAb were determined in all subjects until 12 months postpartum. Levothyroxine was supplemented to maintain euthyroid with periodical checking of thyroid functions. The prevalence of postpartum thyroiditis (PPT), placenta previa, placental abruption, premature rupture of membrane, postpartum haemorrhage, polyhydramnios, oligohydramnios, preterm birth, low birth weight, congenital hypothyroidism, and neonatal diseases were observed in two groups. Results. Of all women, 11.54% had a PPT. The prevalence of PPT was significantly higher in TPOAb-positive than TPOAb-negative group (42.31% versus 7.14%, P < 0.001), with 45.46% and 53.85% of PPT happening at 6 weeks postpartum in TPOAb-positive and TPOAb-negative groups. The incidence of polyhydramnios was significantly higher in TPOAb-positive than TPOAb-negative group (15.38% versus 2.74%, P = 0.02). Conclusion. Pregnant women with TPOAb-positive had increased risk of PPT, predominantly happening at 6 weeks postpartum. TPOAb was associated with increased incidence of polyhydramnios and the underlying mechanisms required further investigation. Earlier screening of thyroid function during pregnancy and postpartum was warranted in our region. PMID- 26884760 TI - Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects. AB - Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity ([Formula: see text]) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI: 36.6 +/- 4.1 kg.m(-1)) and sixteen SO subjects (BMI: 37.0 +/- 7.3 kg.m(-1)) were compared with sixteen T2DM subjects (BMI: 37.7 +/- 5.6 kg.m(-1)). All groups performed an incremental exercise test on a treadmill according to their physical ability. [Formula: see text], %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover, [Formula: see text], %[Formula: see text], %HRmax, %HRR, DeltaHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort ([Formula: see text], %HRmax, and METmax) in all groups. On the contrary, [Formula: see text], %[Formula: see text], %HRmax, %HRR, DeltaHR, and METivt were significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p < 0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions. PMID- 26884761 TI - Circulating Visfatin in Hypothyroidism Is Associated with Free Thyroid Hormones and Antithyroperoxidase Antibodies. AB - We hypothesized that regulation of visfatin in hypothyroidism might be altered by coexisting chronic autoimmune thyroiditis. This is a prospective case-control study of 118 subjects. The autoimmune study group (AIT) consisted of 39 patients newly diagnosed with hypothyroidism in a course of chronic autoimmune thyroiditis. The nonautoimmune study group (TT) consisted of 40 patients thyroidectomized due to the differentiated thyroid cancer staged pT1. The control group comprised 39 healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Exclusion criteria consisted of other autoimmune diseases, active neoplastic disease, diabetes mellitus, and infection, which were reported to alter visfatin level. Fasting blood samples were taken for visfatin, TSH, free thyroxine (FT4), free triiodothyronine (FT3), antithyroperoxidase antibodies (TPOAb), antithyroglobulin antibodies (TgAb), glucose, and insulin levels. The highest visfatin serum concentration was in AIT group, and healthy controls had visfatin level higher than TT (p = 0.0001). Simple linear regression analysis revealed that visfatin serum concentration was significantly associated with autoimmunity (beta = 0.1014; p = 0.003), FT4 (beta = 0.05412; p = 0.048), FT3 (beta = 0.05242; p = 0.038), and TPOAb (beta = 0.0002; p = 0.0025), and the relationships were further confirmed in the multivariate regression analysis. PMID- 26884762 TI - The Association of Peroxisome Proliferator-Activated Receptor delta and Additional Gene-Gene Interaction with C-Reactive Protein in Chinese Population. AB - Aims. To examine the association between 4 single nucleotide polymorphisms (SNPs) of peroxisome proliferator-activated receptors delta (PPARdelta) polymorphisms and C-reactive protein (CRP) level and additional gene-gene interaction. Methods. Line regression analysis was performed to verify polymorphism association between SNP and CRP levels. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the interaction. Results. A total of 1028 subjects (538 men, 490 women) were selected. The carriers of the C allele (TC or CC) of rs2016520 were associated with a significant decreased level of CRP, regression coefficients was -0.338, and standard error was 0.104 (p = 0.001). The carriers of the G allele (CG or GG) of rs9794 were also significantly associated with decreased level of CRP, regression coefficients was -0.219, and standard error was 0.114 (p = 0.012). We also found a potential gene-gene interaction between rs2016520 and rs9794. Subjects with rs2016520-TC or CC, rs9794-CG or GG genotypes have lowest CRP level, difference (95% CI) = -0.50 (-0.69 to -0.21) (p < 0.001), compared to subjects with rs2016520-TT and rs9794-CC genotypes. Conclusions. rs2016520 and rs9794 minor allele of PPARdelta and combined effect between the two SNP were associated with decreased CRP level. PMID- 26884763 TI - Antibacterial Effect of Hydroalcoholic Extract of Punica granatum Linn. Petal on Common Oral Microorganisms. AB - Objectives. This study aimed to assess the effect of hydroalcoholic extract of Punica granatum Linn. (P. granatum) petal on Streptococcus sanguinis, Streptococcus mutans, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis. Materials and Methods. In this in vitro study, P. granatum extract was prepared using powdered petals and water-ethanol solvent. Antibacterial effect of the extract, chlorhexidine (CHX), and ampicillin was evaluated on brain heart infusion agar (BHIA) using the cup-plate method. By assessing the diameter of the growth inhibition zone, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined for the above-mentioned bacteria. Results. Hydroalcoholic extract of P. granatum petal had inhibitory effects on the proliferation of all five bacterial strains with maximum effect on S. mutans with MIC and MBC of 3.9 mg/mL. The largest growth inhibition zone diameter belonged to S. sanguinis and the smallest to E. faecalis. Ampicillin and CHX had the greatest inhibitory effect on S. sanguinis. Conclusions. Hydroalcoholic extract of P. granatum had a significant antibacterial effect on common oral bacterial pathogens with maximum effect on S. mutans, which is the main microorganism responsible for dental plaque and caries. PMID- 26884764 TI - Preparation and Evaluation of Gelatin-Chitosan-Nanobioglass 3D Porous Scaffold for Bone Tissue Engineering. AB - The aim of the present study was to prepare and characterize bioglass-natural biopolymer based composite scaffold and evaluate its bone regeneration ability. Bioactive glass nanoparticles (58S) in the size range of 20-30 nm were synthesized using sol-gel method. Porous scaffolds with varying bioglass composition from 10 to 30 wt% in chitosan, gelatin matrix were fabricated using the method of freeze drying of its slurry at 40 wt% solids loading. Samples were cross-linked with glutaraldehyde to obtain interconnected porous 3D microstructure with improved mechanical strength. The prepared scaffolds exhibited >80% porosity with a mean pore size range between 100 and 300 microns. Scaffold containing 30 wt% bioglass (GCB 30) showed a maximum compressive strength of 2.2 +/- 0.1 MPa. Swelling and degradation studies showed that the scaffold had excellent properties of hydrophilicity and biodegradability. GCB 30 scaffold was shown to be noncytotoxic and supported mesenchymal stem cell attachment, proliferation, and differentiation as indicated by MTT assay and RUNX 2 expression. Higher cellular activity was observed in GCB 30 scaffold as compared to GCB 0 scaffold suggesting the fact that 58S bioglass nanoparticles addition into the scaffold promoted better cell adhesion, proliferation, and differentiation. Thus, the study showed that the developed composite scaffolds are potential candidates for regenerating damaged bone tissue. PMID- 26884765 TI - Eucalyptus Tree: A Potential Source of Cryptococcus neoformans in Egyptian Environment. AB - In Egypt, the River Red Gum (Eucalyptus camaldulensis) is a well-known tree and is highly appreciated by the rural and urban dwellers. The role of Eucalyptus trees in the ecology of Cryptococcus neoformans is documented worldwide. The aim of this survey was to show the prevalence of C. neoformans during the flowering season of E. camaldulensis at the Delta region in Egypt. Three hundred and eleven samples out of two hundred Eucalyptus trees, including leaves, flowers, and woody trunks, were collected from four governorates in the Delta region. Thirteen isolates of C. neoformans were recovered from Eucalyptus tree samples (4.2%). Molecular identification of C. neoformans was done by capsular gene specific primer CAP64 and serotype identification was done depending on LAC1 gene. This study represents an update on the ecology of C. neoformans associated with Eucalyptus tree in Egyptian environment. PMID- 26884766 TI - Nonthrombotic Pulmonary Embolism: A Potential Complication of Polyacrylamide Hydrogel Cosmetic Injection. AB - Context. Polyacrylamide hydrogel (PAAG) has gained importance as a synthetic soft tissue filling agent. It has been commonly employed by physicians in Europe for facial contouring and soft tissue augmentation. Previously, PAAG is considered nontoxic and well tolerated with a few mild procedural complications. Case Presentation. A 26-year-old female was hospitalized for dry cough, worsening dyspnea, and chest discomfort after 3 hours of multiple PAAG injections in buttocks. The patient's condition deteriorated and rapidly advanced to acute respiratory failure. Therein, the diagnosis of nonthrombotic pulmonary embolism (NTPE) was established on standard set of investigations. She was intubated; corticosteroid and empiric antibiotic therapy was initiated resulting in improvement of her condition. Subsequently, extubation was done, and she was discharged from the hospital after an uneventful recovery. On 1-month follow-up, the patient had no previous symptoms. Conclusion. This report implicates clinicians to maintain a high index of suspicion for NTPE in patients presenting with respiratory symptoms following PAAG usage. PMID- 26884767 TI - Probable Levofloxacin-Induced Thrombocytopenia in a Patient Previously on Ciprofloxacin: A Case Report and Literature Review. AB - Drug-induced thrombocytopenia is a poorly understood, yet common phenomenon widely encountered in clinical practice. We present a case of suspected levofloxacin-induced thrombocytopenia, a rare side effect of a ubiquitous antibiotic, in a patient without similar effect to ciprofloxacin. This report builds upon other isolated case reports of fluoroquinolone-induced thrombocytopenia and demonstrates our algorithmic approach to the issue as well as a literature review pertaining to fluoroquinolone-induced thrombocytopenia. PMID- 26884768 TI - Interventricular Septal Hematoma after Retrograde Intervention for a Chronic Total Occlusion of a Right Coronary Artery: Echocardiographic and Magnetic Resonance Imaging-Diagnosis and Follow-Up. AB - The reverse CART technique provides the potential to modify the retrograde procedure by improving the controlled movement of the retrograde wire and improve the success rates of percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). Development of interventricular hematoma is a rare complication of CTO PCI. A 63-year-old man with effort angina with a right coronary artery CTO lesion underwent PCI by retrograde approach from the LAD to a septal branch. A contrast "stain" was demonstrated surrounding the septal collateral channel used for the retrograde approach at the end of the procedure without symptom. Echocardiography indicated an increased interventricular septum thickness with low echo signals region and decreased contractility. Cardiac magnetic resonance (CMR) imaging using gadolinium showed a diffusely thickened septum with a low signal fusiform neocavitation delimited by an enhanced-signal ring suggesting intraventricular septal dissecting hematoma. After conservative treatment, follow up echocardiogram and CMR showed the resolution of the hematoma without clinical events. This case highlights the potentially lethal complication of septal perforator dissection and hematoma that may cause severe myocardial injury caused by retrograde approach for CTO PCI. PMID- 26884769 TI - Tissue-Derived Stem Cell Research. PMID- 26884771 TI - Is It Time to Review Guidelines for ETT Positioning in the NICU? SCEPTIC-Survey of Challenges Encountered in Placement of Endotracheal Tubes in Canadian NICUs. AB - Objectives. To examine current opinions and practices regarding endotracheal tube placement across several Canadian Neonatal Intensive Care Units. Design. Clinical directors from Canadian Neonatal Network affiliated NICUs and Neonatal-Perinatal Programs across Canada were invited via email to participate in and disseminate the online survey to staff neonatologists, neonatal fellows, respiratory therapists, and nurse practitioners. Result. There is wide variability in the beliefs and practices related to ETT placement. The majority use "weight +6" formula and "aim to black line" on ETT at vocal cords to estimate the depth of an oral ETT and reported estimation as challenging in ELBW infants. The majority agreed that mid-trachea is an ideal ETT tip position; however their preferred position on chest X-ray varied. Many believe that ETT positioning could be improved with more precise ETT markings. Conclusion. Further research should focus on developing more effective guidelines for ETT tip placement in the ELBW infants. PMID- 26884772 TI - Three Dimensional Finite Element Analysis of Distal Abutment Stresses of Removable Partial Dentures with Different Retainer Designs. AB - OBJECTIVES: This finite element method study aimed to compare the amount of stress on an isolated mandibular second premolar in two conventional reciprocal parallel interface designs of removable partial dentures (RPDs) and the same RPD abutment tooth (not isolated). MATERIALS AND METHODS: A Kennedy Class 1, modification 1 RPD framework was simulated on a 3D model of mandible with three different designs: an isolated tooth with a mesial rest, an isolated tooth with mesial and distal rests and an abutment with a mesial rest (which was not isolated); 26 N occlusal forces were exerted bilaterally on the first molar sites. Stress on the abutment teeth was analyzed using Cosmos Works 2009 Software. RESULTS: In all designs, the abutment tooth stress concentration was located in the buccal alveolar crest. In the first model, the von Mises stress distribution in the contact area of I-bar clasp and cervical portion of the tooth was 19 MPa and the maximum stress was 30 MPa. In the second model, the maximum von Mises stress distribution was 15 MPa in the cervical of the tooth. In the third model, the maximum von Mises stress was located in the cervical of the tooth and the distal proximal plate. CONCLUSION: We recommend using both mesial and distal rests on the distal abutment teeth of distal extension RPDs. The abutment of an extension base RPD, which is not isolated in presence of its neighboring more anterior tooth, may have a better biomechanical prognosis. PMID- 26884770 TI - Community-Acquired Rotavirus Gastroenteritis Compared with Adenovirus and Norovirus Gastroenteritis in Italian Children: A Pedianet Study. AB - Background. Rotavirus (RV) is the commonest pathogen in the hospital and primary care settings, followed by Adenovirus (AV) and Norovirus (NV). Only few studies that assess the burden of RV gastroenteritis at the community level have been carried out. Objectives. To estimate incidence, disease characteristics, seasonal distribution, and working days lost by parents of RV, AV, and NV gastroenteritis leading to a family pediatrician (FP) visit among children < 5 years. Methods. 12 month, observational, prospective, FP-based study has been carried out using Pedianet database. Results. RVGE incidence was 1.04 per 100 person-years with the highest incidence in the first 2 years of life. Incidences of AVGEs (1.74) and NVGEs (1.51) were slightly higher with similar characteristics regarding age distribution and symptoms. Risk of hospitalisation, access to emergency room (ER), and workdays lost from parents were not significantly different in RVGEs compared to the other viral infections. Conclusions. Features of RVGE in terms of hospitalisation length and indirect cost are lower than those reported in previous studies. Results of the present study reflect the large variability of data present in the literature. This observation underlines the utility of primary care networks for AGE surveillance and further studies on community acquired gastroenteritis in children. PMID- 26884773 TI - Effect of Topical Fluoride on Surface of Cast Titanium and Nickel-Chromium: An In Vitro Study. AB - OBJECTIVES: The aim of this in-vitro study was to evaluate the effect of topical fluoride on surface of cast titanium and nickel-chromium. MATERIALS AND METHODS: Thirty-nine rectangular specimens of titanium (grade 2) and 39 rectangular specimens of nickel-chromium were cast in equal dimensions and divided into three groups of 13 samples each. Group one specimens of titanium and nickel-chromium were placed in 2% neutral sodium fluoride (NaF) solution for 16 minutes. Group two specimens of titanium and nickel-chromium were immersed in 1.23% acidulated phosphate fluoride (APF) gel for eight minutes. Group three specimens of titanium and nickel-chromium were immersed in distilled water for 16 minutes. The surface roughness of the specimens was evaluated and the data were analyzed using two-way ANOVA and post-hoc comparison test with the level of significance set at 5% (P< 0.05). The surface of the specimens was further analyzed using a scanning electron microscope (SEM) and energy dispersive spectrometer (EDS). RESULTS: Group two titanium specimens showed a statistically significant increase in surface roughness (P<0.05); but no statistically significant increase was noted in the surface roughness of nickel-chromium specimens in groups one, two and three (P>0.05). Qualitative SEM and EDS analyses further revealed the surface corrosion of titanium (group two) and localized mild corrosive pitting of nickel chromium specimens (group two). CONCLUSION: Topical fluoride with acidic pH affects the surface roughness of titanium and to a certain extent, nickel chromium. Neutral NaF solutions cause no significant change in corrosion resistance of titanium or nickel-chromium. PMID- 26884774 TI - Effect of Dietary Vitamin C on Orthodontic Tooth Movement in Rats. AB - OBJECTIVES: Bone remodeling occurs during orthodontic treatment; this process enables tooth movement. Many factors can affect bone remodeling at the cellular level, such as nutritional supplements that can affect tooth movement. The present study was designed to evaluate the effect of dietary vitamin C on orthodontic tooth movement in rats. MATERIALS AND METHODS: This study was carried out on 36 six-week male Wistar rats with a mean weight of 225+/-32 g, which were randomly allocated to two equal groups. Rats in the case group received 1wt% vitamin C in their daily water. Opening springs were placed on the incisor teeth of both case and control groups. After 17 days, rats were sacrificed; the distance between the mesio-incisal angles of these teeth was measured with a digital caliper. Histological sections were made containing incisor teeth and alveolar bone and stained by hematoxylin-eosin. The number of resorption lacunae was evaluated using light microscopy. RESULTS: Our findings showed that the amount of tooth movement in the vitamin C group was significantly higher than that in the control group (P<0.001). The osteoclast counts were significantly higher in vitamin C group (P=0.036). CONCLUSION: Oral vitamin C can increase orthodontic tooth movement in rats with more osteoclast lacunae around root in the pressure area. PMID- 26884775 TI - Effect of Coloring-by-Dipping on Microtensile Bond Strength of Zirconia to Resin Cement. AB - OBJECTIVES: Studies on the effect of coloring procedures on the bond strength of zirconia to resin cement are lacking in the literature. This study evaluated the effect of dipping of zirconia ceramic in different liquid color shades on the microtensile bond strength (MTBS) of zirconia ceramic to resin cement. MATERIALS AND METHODS: This in vitro study was conducted on 100 microbar specimens divided into five groups of B2, C1, D4, A3 and control (not colored). To prepare the microbars, 20 white zirconia ceramic blocks, measuring 5*11*11 mm, were dipped in A3, B2, C1 or D4 liquid color shades for 10 seconds (five blocks for each color shade) and five blocks were not colored as controls. All the zirconia blocks were sintered in a sintering furnace. Composite blocks of similar dimensions were fabricated and bonded to zirconia ceramic blocks using Panavia F 2.0 resin cement. Zirconia-cement-composite blocks were sectioned into microbars measuring 1*1*10 mm. The MTBS of microbars was measured by a testing machine. Data were analyzed using one-way ANOVA and Tukey's test. All tests were carried out at 0.05 level of significance. RESULTS: Statistically significant differences were found among the groups in MTBS (P<0.001). The D4 group had the highest MTBS value (39.16 +/- 6.52 MPa). CONCLUSION: Dipping affected the MTBS of zirconia ceramic to Panavia F 2.0 resin cement; however, a similar pattern of change was not seen due to the different liquid color shades. PMID- 26884776 TI - Morphology and Differentiation of MG63 Osteoblast Cells on Saliva Contaminated Implant Surfaces. AB - OBJECTIVES: Osteoblasts are the most important cells in the osseointegration process. Despite years of study on dental Implants, limited studies have discussed the effect of saliva on the adhesion process of osteoblasts to implant surfaces. The aim of this in vitro study was to evaluate the effect of saliva on morphology and differentiation of osteoblasts attached to implant surfaces. MATERIALS AND METHODS: Twelve Axiom dental implants were divided into two groups. Implants of the case group were placed in containers, containing saliva, for 40 minutes. Then, all the implants were separately stored in a medium containing MG63 human osteoblasts for a week. Cell morphology and differentiation were assessed using a scanning electron microscope and their alkaline phosphatase (ALP) activity was determined. The t-test was used to compare the two groups. RESULTS: Scanning electron microscopic observation of osteoblasts revealed round or square cells with fewer and shorter cellular processes in saliva contaminated samples, whereas elongated, fusiform and well-defined cell processes were seen in the control group. ALP level was significantly lower in case compared to control group (P<0.05). CONCLUSION: Saliva contamination alters osteoblast morphology and differentiation and may subsequently interfere with successful osseointegration. Thus, saliva contamination of bone and implant must be prevented or minimized. PMID- 26884777 TI - Marginal Microleakage of Conventional Fissure Sealants and Self-Adhering Flowable Composite as Fissure Sealant in Permanent Teeth. AB - OBJECTIVES: Application of sealants is a safe and effective way to prevent occlusal caries in the posterior teeth. A successful sealant therapy depends on good isolation. Decreased steps of adhesive application may enable proper isolation and use of self-adhering flowable composites for sealant therapy. This study sought to compare the marginal microleakage of fissure sealants and self adhering flowable composites in permanent teeth. MATERIALS AND METHODS: This in vitro, experimental study was conducted on 60 extracted human premolar teeth. The teeth were divided randomly into two groups of 30. In the first group, fissure sealant (Clinpro, 3M ESPE, USA) was placed on the teeth. In the second group, self-adhering flowable composite (Vertise Flow, Kerr, USA) was applied as the sealant. Then, both groups were immersed in 0.5% fuchsin dye solution for 24 hours. Sectioned samples were observed with a stereomicroscope for the extent of dye penetration. Data were analyzed using SPSS 21 and the Mann-Whitney test (P<0.05). RESULTS: Microleakage in the fissure sealant group was significantly higher than that in the self-adhering flowable composite group (P<0.001). CONCLUSION: Microleakage was less using self-adhering flowable composite compared to conventional fissure sealant; therefore, self-adhering flowable composite can be used as a suitable fissure sealant in permanent teeth. PMID- 26884778 TI - Effect of Enamel Preparation and Light Curing Methods on Microleakage under Orthodontic Brackets. AB - OBJECTIVES: This study aimed to compare the microleakage beneath metallic brackets following two different methods of enamel preparation and light curing. MATERIALS AND METHODS: A total of 120 bovine deciduous lower incisors were randomly divided into four groups of 30 teeth. The preparations were as follows: Group I: Acid etching + Transbond XT primer + direct illumination, group II: acid etching + Transbond XT primer + transillumination, group III: Transbond XT self etching primer + direct illumination and Group IV: Transbond XT self-etching primer + transillumination. Dye penetration was used as the method of microleakage evaluation. Sections made at the enamel-adhesive and adhesive bracket interfaces were evaluated under a stereomicroscope. The Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. The level of significance was set at P<0.05. RESULTS: All groups showed greater microleakage at the gingival in comparison to the incisal margin and the differences were significant among groups with transillumination (P<0.001). No significant differences were observed in the microleakage scores at the gingival and incisal margins in any of the interfaces (P>0.05). Mesiodistal margins of the self etching group with direct illumination showed significantly lower scores in comparison with acid etched group (P<0.05). CONCLUSION: Use of self-etching primers for bonding of orthodontic brackets yields acceptable results if all bracket margins are cured directly. PMID- 26884779 TI - Designing and Implementation of a Course on Successful Dental Practice for Dentists. AB - OBJECTIVES: We aimed to design, implement and evaluate the efficacy of a comprehensive course on non-clinical competencies that dentists must possess for a successful dental practice. MATERIALS AND METHODS: In this interventional before-after study an expert panel of five academic staff members and five general practitioners derived the topics for a course on successful dental practice, and aggregated them in the form of a two-day course. It was held for 46 randomly selected dentists in January 2010, at the School of Dentistry, Tehran University of Medical Sciences. The participants completed an anonymous questionnaire asking about their self-perceived need to receive training in each of the proposed topics and their self-assessed knowledge about each topic before and after attending the course. RESULTS: Participants gave a higher priority to the necessity of training on "ergonomics and professional health" and communication skills in post-test compared to pre-test (P<0.05). The self assessed knowledge of dentists improved significantly after attending the course in seven domains: ergonomics and occupational health, workplace design, documentation principles and IT applications in dentistry, national rules and regulations of dental practice, medical emergencies, dental ethics and communication skills (P<0.05). More than 70% of the participants were completely satisfied or satisfied with practical implication of the course, conformity of the contents with the title and course settings. CONCLUSION: The designed course seemed to be successful in revealing the need of participants for further education. Considering the high satisfaction rate of the attendants, this course can serve as a model for continuing education purposes. PMID- 26884780 TI - Oral Myiasis: A Rare Case Report and Literature Review. AB - Myiasis is a rare disease caused by infestation of tissue by larvae of flies. Oral myiasis is still "rare" and "unique" owing to the fact that oral cavity rarely provides the necessary habitat for a larval lifecycle. Herein, we present a case of extensive gingival myiasis in a 12-year-old mentally retarded, epileptic child as well as a literature review. PMID- 26884781 TI - Regenerative Endodontic Treatment: Report of Two Cases with Different Clinical Management and Outcomes. AB - Endodontic intervention in necrotic immature permanent teeth is usually a clinical challenge. With appropriate case selection, regenerative treatment can be effective, providing a desirable outcome. However, there is still no consensus on the optimal disinfection protocol or the method to achieve predictable clinical outcome. This article presents two cases of regenerative treatment in necrotic immature teeth, using mineral trioxide aggregate (MTA) and Biodentine(TM) as coronal barriers and different irrigants, which led to different clinical outcomes. PMID- 26884782 TI - A Comparative Study of Group Behavioral Activation and Cognitive Therapy in Reducing Subsyndromal Anxiety and Depressive Symptoms. AB - OBJECTIVE: This study compared the effectiveness of two group treatments, behavioral activation (BA) and cognitive therapy (CT), in reducing subsyndromal anxiety and depressive symptoms in a sample of Iranian university students. METHOD: Twenty-seven Iranian university students who scored 18 or higher on the depression subscale and 16 or higher on the anxiety subscale of the Depression, Anxiety, and Stress Scale (DASS-42) were randomly assigned into treatment groups. One group received 8 sessions of BA (n = 14), and the other received 8 sessions of group CT (n = 13). RESULT: Analysis of covariance revealed that the BA group had a significantly greater reduction in depressive symptoms than the CT group. However, there were no significant differences between the two groups in the levels of anxiety, stress symptoms or functional impairment after treatment. CONCLUSION: This study found evidence for the effectiveness of BA in reducing anxiety, depressive and stress symptoms and functional impairment compared to CT. BA was more effective than CT in improving depressive symptoms and was as effective as CT in decreasing anxiety, stress and functional impairment. BA is also a cost-effective intervention, particularly in group formats. PMID- 26884783 TI - The Role of Defense Mechanisms, Personality and Demographical Factors on Complicated Grief following Death of a loved one by Cancer. AB - OBJECTIVE: Identification of the risk factors and psychological correlates of prolonged grief disorder is vital for health promotions in relatives of persons who died of cancer. The aim of this research was to investigate the role of defense mechanisms, character dimension of personality and demographic factors on complicated grief following a loss of a family member to cancer. METHOD: A number of 226 persons who had lost a family member to cancer in a cancer institute at Tehran University of Medical Science were selected through compliance sampling and completed the Inventory of complicated Grief-Revised (ICG-R), the Defense Styles Questionnaire (DSQ), the Character dimension of Temperament and Character Inventory (TCI), and the Demographical questionnaire. Data were analyzed by stepwise multiple regression analysis, using the PASW version 18. RESULTS: Findings revealed that neurotic defense style had a significant positive predictive role in the complicated grief; and cooperativeness, age of the deceased person, self-transcendence and mature defense style had a significant negative predictive role in complicated grief (p<0.001). R2 was 0.73 for the final model (p<.001). CONCLUSION: The results revealed that two character dimensions (low cooperativeness and self-transcendence), high neurotic defense style and young age of the deceased person were involved in the psychopathological course of the complicated and prolonged grief. It was concluded that personality characteristics of the grieving persons and demographics of the deceased person should be addressed in designing tailored interventions for complicated grief. PMID- 26884784 TI - Efficacy of Mindfulness-Based Cognitive Therapy on Quality of Life of Mothers of Children with Cerebral Palsy. AB - OBJECTIVE: The findings demonstrated that parents of children with cerebral palsy experience elevated levels of distress, depression, anxiety, posttraumatic stress symptom and subjective symptom of stress and low quality of life. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of this condition. Many studies have shown that Mindfulness Based Cognitive Therapy (MBCT) is an intervention that has shown efficacy in improving quality of life. In this study, the effect of Mindfulness -Based Cognitive Therapy (MBCT) on increasing quality of life in mothers of children with cerebral palsy has been examined. METHOD: Three mothers of CP children with low scores on quality of life in WHOQOL-BREF inventory participated in this single- case study. RESULTS: Findings revealed that the MBCT program elevated quality of life of the participants. The improvement quotient for quality of life of each participant was good . CONCLUSION: The results have implication for efficacy of mindfulness for improvement of psychosocial life of families of children with cerebral palsy. PMID- 26884785 TI - Evaluation of Cerebral Cortex Function in Clients with Bipolar Mood Disorder I (BMD I) Compared With BMD II Using QEEG Analysis. AB - OBJECTIVE: Early diagnosis of type I and type II bipolar mood disorder is very challenging particularly in adolescence. Hence, we aimed to investigate the cerebral cortex function in these patients, using quantitative electroencephalography analysis to obtain significant differences between them. METHODS: Thirty- eight adolescents (18 patients with bipolar disorder I and 20 with BMD II) participated in this study. We recorded the electroencephalogram signals based on 10-20 international system by 21 electrodes in eyes open and eyes closed condition resting conditions. Forty seconds segments were selected from each recorded signals with minimal noise and artifacts. Periodogram Welch was used to estimate power spectrum density from each segment. Analysis was performed in five frequency bands (delta, theta, alpha, beta and gamma), and we assessed power, mean, entropy, variance and skewness of the spectrums, as well as mean of the thresholded spectrum and thresholded spectrogram. We only used focal montage for comparison. Eventually, data were analyzed by independent Mann Whitney test and independent t test. RESULTS: We observed significant differences in some brain regions and in all frequency bands. There were significant differences in prefrontal lobe, central lobe, left parietal lobe, occipital lobe and temporal lobe between BMD I and BMD II (P < 0.05). In patients with BMD I, spectral entropy was compared to patients with BMD II. The most significant difference was observed in the gamma frequency band. Also, the power and entropy of delta frequency band was larger in the left parietal lobe in the BMD I patients compared to BMD II patients (P < 0.05). In the temporal lobe, significant differences were observed in the spectrum distribution of beta and gamma frequency bands (P < 0.05). CONCLUSION: The QEEG and entropy measure are simple and available tools to help detect cerebral cortex deficits and distinguish BMD I from BMD II. PMID- 26884786 TI - Long Term Effects of Mindfulness on Quality of life in Irritable Bowel Syndrome. AB - OBJECTIVES: This study aimed to investigate the long-term effects of mindfulness based therapy on improving life quality of patients with irritable bowel syndrome. METHOD: This was an experimental study including 24 patients (12 from each group) with IBS syndrome were selected based on the ROMEIII criteria and were randomly placed in the test and control groups. In both groups, the scales of the IBS-QOL34 Questionnaire were applied as assessment tool. Experiment group was subjected to the MFT (mindfulness-based therapy), while the control group received no intervention. After the two-month follow up, both groups were once again evaluated through the IBS-QOL34 scales. RESULTS: There is not significant difference between trial and control group in starting of the study in demographic and quality of life status. The findings of covariance analysis revealed that the difference between the experiment and the control groups at follow-up was significant (p = 0.01). The results showed that the MFT has long term effects on the life quality of patients suffering from IBS. CONCLUSION: The MFT could be considered as a new, effective and stable method in psychotherapy, particularly in psychosomatic disorders such as Irritable Bowel Syndrome. PMID- 26884787 TI - Memantine versus Methylphenidate in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial. AB - OBJECTIVES: The aim of this randomized clinical trial was to assess the efficacy of memantine versus methylphenidate in the treatment of children with attention deficit hyperactivity disorder. METHOD: Forty participants (34 boys and 6 girls) aged 6-11 who were diagnosed with attention deficit hyperactivity disorder based on (DSM-IV-TR) criteria were selected for this study. The participants were randomly assigned to two groups: group one (n = 22) received memantine and the other group (n = 18) received methylphenidate for six weeks. Treatment outcomes were assessed using the Attention Deficit Hyperactivity Rating Scale and Clinical Global Impression- Severity Scale administered at baseline and at weeks 3 and 6 following the treatment. Also, a two-way repeated measures analysis of variance (time- treatment interaction) was used. RESULTS: At 6 weeks, methylphenidate produced a significantly better outcome on the Parent Rating Scale scores and Clinical Global Impression- Severity than memantine. Side effects were observed more often in the memantine group. However, with respect to the frequency of side effects, the difference between the memantine and methylphenidate groups was not significant. The most common side effects associated with memantine are appetite suppression, headache, vomiting, nausea and fatigue. CONCLUSION: The results of this study revealed that although memantine was less effective than methylphenidate in the treatment of attention deficit hyperactivity disorder, it may be considered as an alternative treatment. PMID- 26884788 TI - Psychometric Properties of the Persian Version of the Difficulties in Emotion Regulation Scale) DERS-6 & DERS-5- Revised (in an Iranian Clinical Sample. AB - OBJECTIVE: The purpose of this study was to determine the construct validity and reliability of the two forms of the Persian version of the Difficulties in Emotion Regulation Scale (DERS-6 & DERS-5-revised) in a clinical sample. METHODS: The clinical sample consisted of 181 patients diagnosed with Functional GI Disorders (FGID) who referred to the digestive psychosomatic clinic in Isfahan in 2012. They were selected by census method (In a given period of time). The Persian version of the DERS, the short form of the DASS, and the TAS-20 were used to collect data. RESULTS: The results of the factor structure or construct validity using principal components analysis with varimax rotation recognized 7 factors for the DERS-6 (Goals, Awarness, Impalse, Non Acceptance, Strategy, Clarity, Recognition), and 6 factors for the DERS-5- revised (Non Acceptance, Goals, Impalse, Strategy, Clarity, Recognition) in the clinical sample. They showed the common variance of 59.51% and 59.15%, respectively. Also, the results showed that the concurrent validity of both forms of the DERS and most of their factors, and their reliability in terms of Cronbach-Alpha were favorable. DISCUSSION: Considering the factor structure and favorable psychometric properties of the two scales of DERS-6 & DERS-5-revised, the scales can be used in clinical samples. PMID- 26884789 TI - Identifying Some Risk Factors of Time to Relapses in Schizophrenic Patients using Bayesian Approach with Event-Dependent Frailty Model. AB - OBJECTIVES: Schizophrenia patients often experience relapses once and even more with no limit on number of relapses. The time among relapses are rarely considered in studies. The aim of this study was to identify some risk factors of time to elapses in schizophrenic patients with recurrent events model in survival analysis. METHODS: In a retrospective longitudinal study, the medical records of 159 schizophrenic patients who referred to Razi hospital in Tehran from 2003 to 2005 were conveniently sampled, investigated and followed until the end of 2009. The time to recurrent relapses were considered in weeks. The patients with at least one relapse in this duration were included in the study. Event-dependent frailty model, using Bayesian approach, was applied to fit the data and identify the risk factors of time to relapses. RESULTS: In this recurrent failure time model, the effects of age of onset (95% CI = (0.058, 0.086)), gender (95% CI = (0.146, 0.686)), marital status (95% CI = (0.475, 0.965)) and family history (95% CI = (0.115, 0.543)) were significant on the hazard time to relapses. According to the credible interval of frailty variance, elapsed time to relapse is dependent on patients' characteristics (95% CI = (0.084, 0.369)). Subsequent relapses are likely to be influenced by the occurrence of the first relapse, too (95% CI = (2.504, 3.079)), with decreasing hazard of time to relapse. CONCLUSIONS: Subsequent relapses are likely dependent on the first and previous relapses. Age of onset, gender, marital status and family history are important risk factors influencing hazard of time to relapses. More studies are required to clear out the effect of other covariates with this model. PMID- 26884790 TI - Severity of Anxiety Disorders in Patients with Chronic Obstructive Pulmonary Disease. AB - OBJECTIVE: Patients with chronic physical diseases sometimes show increased loss of function; such patients need more care. Anxiety is a well-known symptom that is prevalent among chronic obstructive pulmonary disease patients that can prolong and increase the risk of hospitalization. The purpose of this study was to evaluate the severity of anxiety in the mentioned patients and to examine the presence of symptoms and appropriate treatment strategies to understand the role of psychological functions in physical patients. Methods : This was a cross sectional study conducted in Masih Daneshvari Hospital. One hundred forty- three patients entered into the project by accessible method and signed the informed consent; they filled demographic information and Hamilton anxiety and depression questionnaires. Data were analyzed by SPSS-16. Results : Of the participants, 68% were above 60 years of age; 78% were male; 89% were married; and 38% were self employed. Also, among the participants, 51% were illiterate; 72% had history of smoking; 46% had history of substance abuse; and 49% had moderate to severe anxiety disorder. Moreover, of the patients with severe anxiety, 41.3% had severe muscle spasms; and severe sleeplessness was found in 38.5% of those with severe anxiety disorder. Severe anxiety related symptoms were found in 20.3% of the patients with severe anxiety disorder. Depressed mood was found in 27.3% of the patients with severe anxiety disorder. Severe physical and muscular signs were found in 35.7% of those with severe anxiety disorder. Conclusion : According to our findings, many chronic diseases such as chronic obstructive pulmonary disease may contain anxiety and depression which result in vulnerability. Therefore, evaluation of anxiety in such patients is of importance for alleviating the disease. PMID- 26884791 TI - Priapism Followed by Discontinuation of Methadone: A rare Case Report. AB - OBJECTIVE: Priapism is defined by persistent, painful penile erection which occurs without sexual stimulation. Methadone is used as an analgesic and is also used in detoxification and maintenance protocol for opioid dependence treatment. Here we will report a case of a male with priapism after rapid discontinuation doses of methadone. CASE PRESENTATION: The case was a young married male who referred to a psychiatry clinic due to long-time spontaneous erections. The patient had no history of mental disorders, trauma or sickle cell anemia. He used to smoke opium for five years and used methadone for four years at a dose of 17 cc daily, which he abruptly discontinued. Then he often experienced spontaneous and painful erections without physical or mental stimulation that caused him shame and embarrassment. CONCLUSION: In this case, chronology indicates that rapid discontinuation of methadone was possibly responsible for the occurrence of priapism. This may have happened due to a compensatory reaction to methadone side effect of erectile dysfunction, followed by its rapid withdrawal. PMID- 26884792 TI - Herbal Formulation C168 Attenuates Proliferation and Induces Apoptosis in HCT 116 Human Colorectal Carcinoma Cells: Role of Oxidative Stress and DNA Damage. AB - The use of herbal formulations has gained scientific interest, particularly in cancer treatment. In this study, the herbal formulation of interest, denoted as C168, is a mixture of eight genera of plants. This study aims to investigate the antiproliferative effect of C168 methanol extract (CME) on various cancer cells and its underlying mechanism of action on the most responsive cell line, namely, HCT 116 cells. CME exerted antiproliferative activities on HCT 116 colorectal carcinoma cells and HepG2 hepatocellular carcinoma cells but not on CCD-841-CoN normal colon epithelial cells, Jurkat E6.1 lymphoblastic leukemic cells, and V79 4 Chinese hamster lung fibroblasts. Further investigation on HCT 116 cells showed that CME induced G2/M cell-cycle arrest and apoptosis. Treatment of CME induced oxidative stress in HCT 116 cells by increasing the superoxide anion level and decreasing the intracellular glutathione. CME also increased tail moment value and H2AX phosphorylation in HCT 116 cells, suggesting DNA damage as an early signal of CME induced apoptosis. Loss of mitochondrial membrane potential in CME treated cells also indicated the involvement of mitochondria in CME induced apoptosis. This study indicated the selectivity of CME toward colon cancer cells with the involvement of oxidative damage as its possible mechanism of action. PMID- 26884793 TI - The Protective Effects of Buzui on Acute Alcoholism in Mice. AB - This study was designed to investigate the role of a traditional buzui recipe in anti-inebriation treatment. Buzui consists of Fructus Schisandrae Chinensis, Fructus Chebulae, Fructus Mume, Fructus Crataegi, Endothelium Corneum Gigeriae Galli, and Excrementum Bombycis. The buzui mixture was delivered by gavage, and ethanol was delivered subsequent to the final treatment. The effects of buzui on the righting reflex, inebriation rates, and the survival curve are depicted. Blood alcohol concentrations, alanine aminotransferase (ALT) levels, aspartate aminotransferase (AST) levels, and alkaline phosphatase (ALP) levels were recorded. The activities of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and superoxide dismutase (SOD), as well as malonaldehyde (MDA) levels, were also measured. Our results demonstrated that a traditional buzui recipe showed significant effects on promoting wakefulness and the prevention of acute alcohol intoxication, accelerating the metabolism of alcohol in the liver and reducing the oxidative damage caused by acute alcoholism. PMID- 26884794 TI - A New Rehabilitation Tool in Fibromyalgia: The Effects of Perceptive Rehabilitation on Pain and Function in a Clinical Randomized Controlled Trial. AB - Introduction/Objective. Fibromyalgia might benefit from a specific tactile and proprioceptive rehabilitation approach. The aim of this study was to perform a randomized controlled trial to determine the efficacy of perceptual surfaces (PS) and physical exercises with regard to chronic pain and physical function in fibromyalgia compared with a control group. Methods. Data from 54 females (18-60 years old) with a diagnosis of fibromyalgia and scoring >5 on the visual analog scale were divided into 3 groups and analyzed: group treated with perceptual surfaces (PS-group), physical exercises group (PE-group), and control group (CG). The Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ), and Fibromyalgia Assessment Scale (FAS) were administered at baseline (T0), at the end of the treatment (T1) (after 10 rehabilitation sessions over a 5 week period), and at the 12-week follow-up (T2). Results. The PS-group experienced a statistically significant improvement versus the CG in FAS and HAQ scores. Good efficacy with respect to pain and function in the PE-group compared with the CG in terms of FAS, HAQ, and FIQ scores was observed. The adherence ratio was 86% for the PE-group and CG and 90% for the PS-group. Conclusions. According to the results, the PS are as promising as the physical exercises, since results were similar. PMID- 26884795 TI - A 70% Ethanol Extract of Mistletoe Rich in Betulin, Betulinic Acid, and Oleanolic Acid Potentiated beta-Cell Function and Mass and Enhanced Hepatic Insulin Sensitivity. AB - We investigated that the long-term consumption of the water (KME-W) and 70% ethanol (KME-E) mistletoe extracts had antidiabetic activities in partial pancreatectomized (Px) rats. Px rats were provided with a high-fat diet containing 0.6% KME-E, 0.6% KME-W, and 0.6% dextrin (control) for 8 weeks. As normal-control, Sham-operated rats were provided with 0.6% dextrin. In cell-based studies, the effects of its main terpenoids (betulin, betulinic acid, and oleanolic acid) on glucose metabolism were measured. Both KME-W and KME-E decreased epididymal fat mass by increasing fat oxidation in diabetic rats. KME-E but not KME-W exhibited greater potentiation of first-phase insulin secretion than the Px-control in a hyperglycemic clamp. KME-E also made beta-cell mass greater than the control by increasing beta-cell proliferation and decreasing its apoptosis. In a euglycemic-hyperinsulinemic clamp, whole-body glucose infusion rate and hepatic glucose output increased with potentiating hepatic insulin signaling in the following order: Px-control, KME-W, KME-E, and normal-control. Betulin potentiated insulin-stimulated glucose uptake via increased PPAR-gamma activity and insulin signaling in 3T3-L1 adipocytes, whereas oleanolic acid enhanced glucose-stimulated insulin secretion and cell proliferation in insulinoma cells. In conclusion, KME-E prevented the deterioration of glucose metabolism in diabetic rats more effectively than KME-W and KME-E can be a better therapeutic agent for type 2 diabetes than KME-W. PMID- 26884796 TI - Effect of Huai Qi Huang on Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells through miR-200a. AB - Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is a vital mechanism of renal fibrosis. Mounting evidence suggests that miR-200a expression decreases in tubular epithelial cells in unilateral ureteral obstruction (UUO) rats. Moreover, it has been demonstrated that Huai Qi Huang (HQH) can ameliorate tubulointerstitial damage in adriamycin nephrosis and delay kidney dysfunction in primary glomerular disease. However, the effect of HQH on EMT of tubular epithelial cells in UUO rats and its molecular mechanism is unclear. In order to explore the effect of HQH on EMT and its molecular mechanism in renal fibrosis, in vitro and in vivo experiments were performed in our study. Our results showed that HQH increased miR-200a expression in UUO rats and in TGF beta1 stimulated NRK-52E cells. Meanwhile, HQH decreased ZEB1 and ZEB2 (the transcriptional repressors of E-cadherin), alpha-SMA expression in renal tubular epithelial cells in vitro and in vivo. Furthermore, we found that HQH protected kidney from fibrosis in UUO rats. The results demonstrated that HQH regulated miR 200a/ZEBs pathway and inhibited EMT process, which may be a mechanism of protecting effect on tubular cells in renal fibrosis. PMID- 26884797 TI - Perceived Benefits of Yoga among Urban School Students: A Qualitative Analysis. AB - This study reports on the findings of a qualitative evaluation of a yoga intervention program for urban middle and high school youth in New York City public and charter schools. Six focus groups were conducted with students who participated in a year-long yoga program to determine their perceptions of mental and physical benefits as well as barriers and challenges. Results show that students perceived the benefits of yoga as increased self-regulation, mindfulness, self-esteem, physical conditioning, academic performance, and stress reduction. Barriers and challenges for a yoga practice include lack of time and space. The extent to which the benefits experienced are interrelated to one another is discussed. Suggestions for future research and school-based programming are also offered. PMID- 26884798 TI - The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts. AB - Osteoporosis has become one of the most prevalent and costly diseases in the world. It is a metabolic disease characterized by reduction in bone mass due to an imbalance between bone formation and resorption. Osteoporosis causes fractures, prolongs bone healing, and impedes osseointegration of dental implants. Its pathological features include osteopenia, degradation of bone tissue microstructure, and increase of bone fragility. In traditional Chinese medicine, the herb Rhizoma Drynariae has been commonly used to treat osteoporosis and bone nonunion. However, the precise underlying mechanism is as yet unclear. Osteoprotegerin is a cytokine receptor shown to play an important role in osteoblast differentiation and bone formation. Hence, activators and ligands of osteoprotegerin are promising drug targets and have been the focus of studies on the development of therapeutics against osteoporosis. In the current study, we found that naringin could synergistically enhance the action of 1alpha,25 dihydroxyvitamin D3 in promoting the secretion of osteoprotegerin by osteoblasts in vitro. In addition, naringin can also influence the generation of osteoclasts and subsequently bone loss during organ culture. In conclusion, this study provides evidence that natural compounds such as naringin have the potential to be used as alternative medicines for the prevention and treatment of osteolysis. PMID- 26884799 TI - The Clinical Effects of Aromatherapy Massage on Reducing Pain for the Cancer Patients: Meta-Analysis of Randomized Controlled Trials. AB - Purpose. Aromatherapy massage is an alternative treatment in reducing the pain of the cancer patients. This study was to investigate whether aromatherapy massage could improve the pain of the cancer patients. Methods. We searched PubMed and Cochrane Library for relevant randomized controlled trials without language limitations between 1 January 1990 and 31 July 2015 with a priori defined inclusion and exclusion criteria. The search terms included aromatherapy, essential oil, pain, ache, cancer, tumor, and carcinoma. There were 7 studies which met the selection criteria and 3 studies were eventually included among 63 eligible publications. Results. This meta-analysis included three randomized controlled trials with a total of 278 participants (135 participants in the massage with essential oil group and 143 participants in the control (usual care) group). Compared with the control group, the massage with essential oil group had nonsignificant effect on reducing the pain (standardized mean difference = 0.01; 95% CI [-0.23,0.24]). Conclusion. Aromatherapy massage does not appear to reduce pain of the cancer patients. Further rigorous studies should be conducted with more objective measures. PMID- 26884800 TI - Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration: Complement activation in AMD. AB - BACKGROUND: The aim of this study was to investigate the plasma levels of complement C3a, C4a, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients' responsiveness to anti-VEGF therapy. RESULTS: Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case-control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4a and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4a and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4a and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy. CONCLUSIONS: Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients. PMID- 26884801 TI - Mucinous tubular and spindle cell carcinoma of the kidney: Diagnosis by fine needle aspiration and review of the literature. AB - Renal mucinous tubular and spindle cell carcinoma (MTSCC) was recently described as a distinct subtype of renal cell carcinoma (RCC) in the 2004 World Health Organization classification of kidney tumors. MTSCC is a rare low grade malignancy with < 100 cases reported in the literature. To the best of our knowledge, there are 5 case reports with a total of 6 patients describing its diagnosis by fine needle aspiration (FNA). All of these cases were diagnosed as conventional RCC on FNA. Subsequent excisions proved them to be MTSCC. We herein report a case in a 67-year-old male. He presented with abdominal pain and was found to have a new colon adenocarcinoma with metastasis to the liver and lungs. The extent of disease made the patient ineligible for surgical excision, and he received chemotherapy. Work-up also revealed a kidney mass which was later biopsied by FNA and core biopsy. The tumor was composed of epithelial and spindled cell components embedded in a myxoid background. It was positive for CK7, AMCAR, vimentin, and epithelial membrane antigen. The tumor was diagnosed as MTSCC. One year later the kidney mass remained stable. However, the patient developed new metastasis to the liver from colonic primary. The kidney mass was not resected. Although rarely encountered in FNA cytology of the kidney, we believe the cytologic features of this tumor are distinctive and are different from conventional and other subtypes of RCC. Therefore, its accurate diagnosis on FNA is possible once pathologists are aware that MTSCC should be considered in the differential diagnosis of kidney tumors. PMID- 26884802 TI - Accuracy of diagnosis of solid pseudopapillary tumor of the pancreas on fine needle aspiration: A multi-institution experience of ten cases. AB - INTRODUCTION: Solid pseudopapillary tumor of the pancreas (SPTP) is a neoplasm of uncertain origin and indolent biologic behavior with distinctive morphological features occurring predominantly in young women. This tumor has an excellent prognosis compared to neuroendocrine and acinar cell carcinoma, which are close differential diagnoses based on morphology, hence making it crucial to diagnose SPTP correctly. OBJECTIVES: To discuss the cytomorphological features of 10 cases of SPTP reported in two institutions and to evaluate the diagnostic accuracy of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) cytology in establishing the diagnosis of SPTP. METHODS: Ten diagnosed cases of SPTP were retrieved from the computerized endoscopy and pathology databases of our two tertiary care institutions. Nine patients had subsequent histological follow-up available. Eight patients underwent EUS-FNA while one patient each had ultrasound and computed tomography-guided FNA. The rapid on-site evaluation was carried out in all 10 cases, and additional material was retained for cell block preparation. Immunohistochemical (IHC) stains ranging from synaptophysin, progesterone receptor, chromogranin, beta-catenin, CD10, and NSE were applied on cell blocks. Histological sections of all resected specimens were reviewed, and findings were correlated with those obtained by FNA. RESULTS: Adequate material was obtained in all ten cases. IHC stains helped to confirm the cytological impression of SPTP. Histological examination of resection specimens, available in 9/10 cases, confirmed the cytological diagnosis. CONCLUSIONS: FNA particularly that obtained with EUS guidance is an effective tool in the accurate diagnosis of SPTP. PMID- 26884803 TI - Metabolism and bioavailability of newly developed dietary fiber materials, resistant glucan and hydrogenated resistant glucan, in rats and humans. AB - BACKGROUND: Resistant glucan (RG) and hydrogenated resistant glucan (HRG) are new dietary fiber materials developed to decrease the risk of metabolic syndrome and lifestyle-related diseases. We investigated the metabolism and bioavailability of RG and HRG using rats and humans. METHODS: Purified RG and HRG were used as test substances. After 25 Wistar male rats (270 g) were fed with an experimental diet (AIN93M diet with the cellulose replaced by beta-corn starch) ad libitum for 1 week, they were used for the experiment involving blood collection and circulating air collection. Ten participants (5 males, 22.5 y, BMI 20.4 kg/m(2); 5 females, 25.8 y, BMI 20.9 kg/m(2)) voluntarily participated in this study. The study was carried out using a within-subject, repeated measures design. Effects of RG and HRG on the response for blood glucose and insulin and hydrogen excretion were compared with those of glucose and a typical nondigestible and fermentable fructooligosaccharide (FOS) in rats and humans. Available energy was evaluated using the fermentability based on breath hydrogen excretion. RESULTS: When purified RG or HRG (400 mg) was administered orally to rats, blood glucose and insulin increased slightly, but less than when glucose was administration (P < 0.05). Hydrogen started to be excreted 120 min after administration of RG with negligibly small peak at 180 min, thereafter excreted scarcely until 1440 min. Hydrogen excretion after HRG administration showed a larger peak than RG at 180 min, but was markedly less than FOS. RG and HRG were excreted in feces, but not urine. When purified RG or HRG (30 g) were ingested by healthy humans, blood glucose and insulin levels increased scarcely. Breath hydrogen excretion increased slightly, but remarkably less than FOS. Ingestion of purified RG or HRG (5 g) to evaluate available energy, increased scarcely glucose and insulin levels and breath hydrogen excretion. Available energy was evaluated as 0 kcal/g for purified RG and 1 kcal/g for HRG. CONCLUSION: The bioavailability was very low in both humans and rats, because oligosaccharide of minor component in purified RG and HRG was metabolized via intestinal microbes but major components with higher molecular weight were metabolized scarcely. Moreover, the ingestion of 30 g of RG or HRG did not induce apparent acute side effects in healthy adults. RG and HRG might potentially be used as new dietary fiber materials with low energy. PMID- 26884804 TI - Erratum to: Vaccination against hepatitis b virus: are Italian medical students sufficiently protected after the public vaccination programme? AB - [This corrects the article DOI: 10.1186/s12995-015-0083-4.]. PMID- 26884805 TI - Consequences of tuberculosis among asylum seekers for health care workers in Germany. AB - BACKGROUND: Immigrants have been contributing to the incidence of tuberculosis (TB) in Germany for many years. The current wave of migration of asylum seekers to Germany may increase that figure. Healthcare workers (HCW) who look after refugees not only in hospitals and medical practices but also in aid projects may be exposed to cases of TB. METHODS: The incremental TB cases arising from imported TB as well as from TB cases that developed later in refugees were calculated in a Markov model over a period of 5 years. Infectious and non infectious susceptible TB and multidrug-resistant TB (MDR-TB) cases were determined separately. In addition, the total amount of latent TB in contact persons and the risk of infection by HCW were estimated. Due to uncertainty of future refugee flows to Europe, different scenarios were considered in univariate and multivariate sensitivity analysis. RESULTS: Assuming a decrease in immigration by half each year to the bottom line of 2014, and in light of the current number of 800,000 asylum seekers, we calculated an additional 10,090 TB cases by the end of the fifth year (5976 cases of infectious pulmonary TB and 143 cases of pulmonary MDR-TB). In case of an unchanging influx of asylum seekers over the 5-year period, 19,031 TB cases would arise, 377 of which infectious MDR TB. Eighty -seven ensuing TB cases would develop in HCW in the same period, 3 of which MDR-TB cases. CONCLUSIONS: Although the total number of TB cases in HCW expected to ensue from the current influx of asylum seekers is rather small, the 3 MDR-TB cases we calculated have to be taken seriously. We consider it essential to increase awareness of protective measures such as respiratory masks and, in the event of documented exposure, of supply-oriented occupational health screening. PMID- 26884806 TI - Phenomics for photosynthesis, growth and reflectance in Arabidopsis thaliana reveals circadian and long-term fluctuations in heritability. AB - BACKGROUND: Recent advances in genome sequencing technologies have shifted the research bottleneck in plant sciences from genotyping to phenotyping. This shift has driven the development of phenomics, high-throughput non-invasive phenotyping technologies. RESULTS: We describe an automated high-throughput phenotyping platform, the Phenovator, capable of screening 1440 Arabidopsis plants multiple times per day for photosynthesis, growth and spectral reflectance at eight wavelengths. Using this unprecedented phenotyping capacity, we have been able to detect significant genetic differences between Arabidopsis accessions for all traits measured, across both temporal and environmental scales. The high frequency of measurement allowed us to observe that heritability was not only trait specific, but for some traits was also time specific. CONCLUSIONS: Such continuous real-time non-destructive phenotyping will allow detailed genetic and physiological investigations of the kinetics of plant homeostasis and development. The success and ultimate outcome of a breeding program will depend greatly on the genetic variance which is sampled. Our observation of temporal fluctuations in trait heritability shows that the moment of measurement can have lasting consequences. Ultimately such phenomic level technologies will provide more dynamic insights into plant physiology, and the necessary data for the omics revolution to reach its full potential. PMID- 26884807 TI - LEAFDATA: a literature-curated database for Arabidopsis leaf development. AB - BACKGROUND: In the post-genomic era, biological databases provide an easy access to a wide variety of scientific data. The vast quantity of literature calls for curated databases where existing knowledge is carefully organized in order to aid novel discoveries. Leaves, the main photosynthetic organs are not only vital for plant growth but also essential for maintaining the global ecosystem by producing oxygen and food. Therefore, studying and understanding leaf formation and growth are key objectives in biology. Arabidopsis thaliana to this date remains the prime experimental model organism in plant science. DESCRIPTION: LEAFDATA was created as an easily accessible and searchable web tool to assemble a relevant collection of Arabidopsis leaf literature. LEAFDATA currently contains 13,553 categorized statements from 380 processed publications. LEAFDATA can be searched for genes of interest using Arabidopsis Genome Initiative identifiers, for selected papers by means of PubMed IDs, authors and specific keywords. The results page contains details of the original publications, text fragments from the curated literature grouped according to information types and direct links to PubMed pages of the original papers. CONCLUSIONS: The LEAFDATA database offers access to searchable entries curated from a large number of scientific publications. Due to the unprecedented details of annotations and the fact that LEAFDATA already provides records about approximately 1600 individual loci, this database is useful for the entire plant research community. PMID- 26884808 TI - Rescaled Local Interaction Simulation Approach for Shear Wave Propagation Modelling in Magnetic Resonance Elastography. AB - Properties of soft biological tissues are increasingly used in medical diagnosis to detect various abnormalities, for example, in liver fibrosis or breast tumors. It is well known that mechanical stiffness of human organs can be obtained from organ responses to shear stress waves through Magnetic Resonance Elastography. The Local Interaction Simulation Approach is proposed for effective modelling of shear wave propagation in soft tissues. The results are validated using experimental data from Magnetic Resonance Elastography. These results show the potential of the method for shear wave propagation modelling in soft tissues. The major advantage of the proposed approach is a significant reduction of computational effort. PMID- 26884809 TI - Implementation of the Rank-Weighted Co-localization (RWC) algorithm in multiple image analysis platforms for quantitative analysis of microscopy images. AB - BACKGROUND: Quantitative co-localization studies strengthen the analysis of fluorescence microscopy-based assays and are essential for illustrating and understanding many cellular processes and interactions. In our earlier study, we presented a rank-based intensity weighting scheme for the quantification of co localization between structures in fluorescence microscopy images. This method, which uses a combined pixel co-occurrence and intensity correlation approach, is superior to conventional algorithms and provides a more accurate quantification of co-localization. FINDINGS: In this brief report we provide the source code and implementation of the rank-weighted co-localization (RWC) algorithm in three (two open source and one proprietary) image analysis platforms. The RWC algorithm has been implemented as a plugin for ImageJ, a module for CellProfiler and an Acapella script for Columbus image analysis software tools. CONCLUSIONS: We have provided with a web resource from which users can download plugins and modules implementing the RWC algorithm in various commonly used image analysis platforms. The implementations have been designed for easy incorporation into existing tools in a 'ready-for-use' format. The resources can be accessed through the following web link: http://simpsonlab.pbworks.com/w/page/48541482/Bioinformatic_Tools. PMID- 26884810 TI - Effectiveness of a cognitive behavioural therapy-based anxiety prevention programme for children: a preliminary quasi-experimental study in Japan. AB - BACKGROUND: As children's mental health problems become more complex, more effective prevention is needed. Though various anxiety and depression prevention programmes based on cognitive behavioural therapy (CBT) were developed and evaluated in Europe, North America, and Australia recently, there are no programmes in Japan. This study developed a CBT programme for Japanese children and tried to verify its effectiveness in reducing anxiety. METHODS: A CBT-based anxiety prevention programme, 'Journey of the Brave', was developed to prevent anxiety disorders for Japanese children. Children from 4th through 6th grades (9 12 years old) in Japanese elementary schools and their parents (13 sample pairs) were the intervention group. For comparison purposes, 16 pairs were the control group. Ten weekly programme sessions and two follow-ups were conducted. Children's anxiety levels in both groups were evaluated by child and parent self reports using the spence children anxiety scale (SCAS) three times: pre-programme (baseline), post-programme, and 3 months following the end of the programme. RESULTS: At 3-month follow-up, no significant difference was shown between the intervention and control groups on children's SCAS scores in changes from baseline by using mixed-effects model for repeated measures analysis (SCAS-C: 8.92 (95 % CI = -14.12 to -3.72) and -3.17 (95 % CI = -8.02 to 1.66) respectively; the between group difference was 5.747 (95 % CI = -1.355 to -12.85, p = 0.062). On the other hand, significant reduction was shown in the intervention group on parents' SCAS (SCAS-P) scores in change from baseline 9.554 (95 % CI = -12.91 to -6.19) and 0.154 (95 % CI = -2.88 to 3.19) respectively; the between group difference was 9.709 (95 % CI = 5.179 to 14.23, p = 0.0001). CONCLUSION: These preliminary results suggest this anxiety prevention programme for Japanese children was partially effective from parents' evaluations. However, it is important to note that this study was conducted on a small sample with unbalanced groups at pre-intervention with no randomization. The positive results may require discounting due to the research limitations. A larger-scale study of the programme in elementary school classes to verify its effectiveness with a more rigorous research design is necessary. TRIAL REGISTRATION: UMIN-CTR UMIN000009021. PMID- 26884811 TI - Erratum to: SorGSD: a sorghum genome SNP database. AB - [This corrects the article DOI: 10.1186/s13068-015-0415-8.]. PMID- 26884812 TI - Effects of the surface physico-chemical properties and the surface textures on the initial colonization and the attached growth in algal biofilm. AB - BACKGROUND: Algal biofilm reactors represent a promising cultivation system that can economically produce biomass without the need for expensive harvesting operations. A critical component of algal biofilm systems is the material used for attachment. This research reports a comprehensive study of the effects of material surface physico-chemical properties, the surface texture, and their interactions on the initial colonization and the long-term attached growth in algal biofilm systems. A total of 28 materials with a smooth surface were tested for initial cell colonization and it was found that the tetradecane contact angle of the materials had a good correlation with cell attachment. The effects of surface texture were evaluated using mesh materials (nylon, polypropylene, high density polyethylene, polyester, aluminum, and stainless steel) with openings ranging from 0.05 to 6.40 mm. RESULTS: The mesh materials with an opening of 0.5 mm resulted in the highest attachment. The interaction of surface physico chemical properties and surface texture, and their co-effects on the cell attachment, was quantitatively described using a second-order polynomial regression. The long-term algal attached growth for the different materials showed a trend similar to that found in initial colonization. CONCLUSIONS: Collectively, nylon and polypropylene mesh with 0.50-1.25 mm openings resulted in the best initial colonization and long-term attached growth, with a 28-30 g m(-2) biomass yield and 4.0-4.3 g m(-2) day biomass productivity being achieved on a pilot-scale revolving algal biofilm system. PMID- 26884813 TI - Echinomycin did not affect the safety of fracture healing: an experimental pilot study on a murine femur fracture model. AB - BACKGROUND: There is a need for effective drugs in the prevention and treatment of heterotopic ossifications (HO) after fractures. Echinomycin has been shown to prevent formation of HO in an animal model. However, before it may be considered as an option against HO, it needs to be studied whether it prevents fracture healing similar to non-steroidal anti-inflammatory drugs (NSAIDS). Therefore, the hypothesis was that echinomycin prevents fracture healing and callus formation. METHODS: In an experimental murine pilot study, standard blunt femur fractures were induced and retrograde intramedullary compression fixation of the femur was performed. The treatment group (n = 8) received echinomycin (0.3 mg/kg body weight) and the control group (n = 8) did not receive echinomycin. The fractures and implant positions were verified by conventional X-rays immediately postoperatively. As the primary outcome variable, fracture healing (osseous consolidation) was evaluated by conventional X-rays and micro-computed tomography (CT) scans after ten weeks and graded as healed, partial or complete pseudarthrosis. The secondary outcome, callus formation, was graded semi quantitatively from 0 (mostly absent) to 3 (maximum). RESULTS: Fracture healing was present in all living cases after ten weeks concerning the treatment group. Partial pseudarthrosis was seen in two cases, one in the treatment and another one in the control group. Complete pseudarthrosis was seen in one case of the control group after an open fracture. Callus formation was similar in both groups with a mean grade of 1.5 within each group. Two cases of the treatment group died. CONCLUSION: As a novel finding, echinomycin did not inhibit fracture healing or callus formation in this in vivo murine standard femur fracture model pilot study. Further studies involving a larger number of cases, quantitative assessment with CT scans and histopathological analysis are needed before generalizing the results of this pilot study. PMID- 26884814 TI - Copy number variations in 119 Chinese children with idiopathic short stature identified by the custom genome-wide microarray. AB - BACKGROUND: Idiopathic short stature (ISS) refers to short stature with no evident etiologies. The custom genome-wide microarray specifically designed to cover height-related genes may be helpful to detect copy number variations (CNVs) in ISS patients, which may be missed by the general microarray. The aim of the study was to validate the applicability of the custom microarray and to analyze CNVs in Chinese ISS children. RESULTS: Sixty non-polymorphic CNVs were identified in 119 ISS patients. There were 13 small CNVs with a size below 50 kb, accounting for 21.7 % of all the CNVs (13/60). Five pathogenic or possibly pathogenic CNVs were detected in five patients, including deletions at 22q11.21, duplications at 4q11-q13.1, 4q12 and Yp11.32-p11.2. Taking only the pathogenic variants into account, the diagnostic yield was 2.5 % (3/119). The TMEM165, POLR2B and PDGFRA genes were analyzed as candidate genes. A 15 kb deletion in the RASA2 gene was of interest for further investigation. CONCLUSIONS: This study showed that the custom microarray is applicable to detect CNVs in patients with short stature. Candidate genes and CNVs detected in ISS patients may be helpful for CNV analysis of short stature, especially in East Asian population. PMID- 26884815 TI - Neck circumference as a risk factor of screen-detected diabetes mellitus: community-based study. AB - BACKGROUND: Whereas an increase of neck circumference (NC) had been recently identified as a new independent cardiovascular disease (CVD) and metabolic syndrome risk factor, similar assessments concerning screen-detected diabetes mellitus (SDDM) have not been made. Thyroid gland volume (ThV) can potentially affect NC however the significance of this influence concerning the risk of NC related disease is unknown. METHODS: We performed a ThV-adjusted evaluation of NC within a population-based investigation of SDDM and impaired glucose regulation (IGR) prevalence. This study contains fasting plasma glucose (FPG) and 75 g 2-h glucose tolerance test results (2-hPG) of 196 residents of Kyiv region, Ukraine, randomly selected from the rural population older than 44 y.o. who were not registered as diabetes mellitus patients. Standard anthropometric (height; weight; blood pressure; waist, hip circumferences), NC and ultrasonography ThV measurements were performed, hypotensive medication, CVD events and early life nutrition history considered. HbA1c was measured, if FPG/2-hPG reached 7.0/11.1 mmol/l respectively; HbA1c level 6.5 % was considered to be SDDM diagnostic; IGR if FPG/2-hPG reached 6.1/7.8 but less than 7.0/11.1 mmol/l respectively. RESULTS: Neck circumference among women with normal FPG/2-hPG was 35 (33-36) cm, IGR 36 (34.5-38) cm, SDDM HbA1c < 6.5 % 42 (40-43) cm, HbA1c > 6.5 % 42.5 (40-44) cm, p < 0.001, and for men from the same groups 38.5 (36.5-41.5) cm; 39 (37-42) cm; 42 (40-43) cm; 42.5 (40-44) cm, p = 0.063; medians (QI-QIII). Gender-adjusted logistic regression OR for SDDM HbA1c > 6.5 % vs. normal FPG/2-hPG category depending of NC as a continued variable, equaled to 1.60 (95 % CI 1.27-2.02) per cm. Additional adjusting by ThV, body mass or waist/hip index, high blood pressure, acute CVD events, or starvation history did not significantly influence this risk. CONCLUSION: Neck circumference is a new risk factor of SDDM that is independent from other indicators of adipose tissue distribution as well as from the ThV. PMID- 26884816 TI - Magnetic Nanoparticles with High Specific Absorption Rate at Low Alternating Magnetic Field. AB - This paper describes the synthesis and properties of a new type of magnetic nanoparticle (MNP) for use in the hyperthermia treatment of tumors. These particles consist of 2-4 nm crystals of gamma-Fe2O3 gathered in 20-40 nm aggregates with a coating of carboxymethyl-dextran, producing a zetasize of 110 120 nm. Despite their very low saturation magnetization (1.5-6.5 emu/g), the specific absorption rate (SAR) of the nanoparticles is 22-200 W/g at applied alternating magnetic field (AMF) with strengths of 100-500 Oe at a frequency of 160 kHz. PMID- 26884819 TI - When is a mutation not a mutation: the case of the c.594-2A>C splice variant in a woman harbouring another BRCA1 mutation in trans. AB - Since the identification of BRCA1 there has only ever been described two bi allelic mutation carriers, one of whom was subsequently shown to be a mono allelic carrier. The second patient diagnosed with two BRCA1 mutations appears to be accurate but there remain some questions about the missense variant identified in that patient. In this report we have identified a woman who is a bi-allelic mutation carrier of BRCA1 and provide an explanation as to why this patient has a phenotype very similar to that of any mono-allelic mutation carrier. The splice variant identified in this patient appears to be associated with the up regulation of a BRCA1 splice variant that rescues the lethality of being a double mutant. The consequences of the findings of this report may have implications for mutation interpretation and that could serve as a model for not only BRCA1 but also for other autosomal dominant disorders that are considered as being embryonically lethal. PMID- 26884818 TI - DNA methylation and hormone receptor status in breast cancer. AB - BACKGROUND: We examined whether differences in tumor DNA methylation were associated with more aggressive hormone receptor-negative breast cancer in an ethnically diverse group of patients in the Breast Cancer Care in Chicago (BCCC) study and using data from The Cancer Genome Atlas (TCGA). RESULTS: DNA was extracted from formalin-fixed, paraffin-embedded samples on 75 patients (21 White, 31 African-American, and 23 Hispanic) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N = 22/75). DNA methylation was analyzed at 1505 CpG sites within 807 gene promoters using the Illumina GoldenGate assay. Differential DNA methylation as a predictor of hormone receptor status was tested while controlling for false discovery rate and assigned to the gene closest to the respective CpG site. Next, those genes that predicted ER/PR status were validated using TCGA data with respect to DNA methylation (validation dataset), and correlations between CpG methylation and gene expression were examined. In the training dataset, 5.7 % of promoter mean methylation values (46/807) were associated with receptor status at P < 0.05; for 88 % of these (38/46), hypermethylation was associated with receptor-positive disease. Hypermethylation for FZD9, MME, BCAP31, HDAC9, PAX6, SCGB3A1, PDGFRA, IGFBP3, and PTGS2 genes most strongly predicted receptor-positive disease. Twenty-one of 24 predictor genes from the training dataset were confirmed in the validation dataset. The level of DNA methylation at 19 out 22 genes, for which gene expression data were available, was associated with gene activity. CONCLUSIONS: Higher levels of promoter methylation strongly correlate with hormone receptor positive status of breast tumors. For most of the genes identified in our training dataset as ER/PR receptor status predictors, DNA methylation correlated with stable gene expression level. The predictors performed well when evaluated on independent set of samples, with different racioethnic distribution, thus providing evidence that this set of DNA methylation biomarkers will likely generalize to prospective patient samples. PMID- 26884817 TI - FluoroNanogold: an important probe for correlative microscopy. AB - Correlative microscopy is a powerful imaging approach that refers to observing the same exact structures within a specimen by two or more imaging modalities. In biological samples, this typically means examining the same sub-cellular feature with different imaging methods. Correlative microscopy is not restricted to the domains of fluorescence microscopy and electron microscopy; however, currently, most correlative microscopy studies combine these two methods, and in this review, we will focus on the use of fluorescence and electron microscopy. Successful correlative fluorescence and electron microscopy requires probes, or reporter systems, from which useful information can be obtained with each of the imaging modalities employed. The bi-functional immunolabeling reagent, FluoroNanogold, is one such probe that provides robust signals in both fluorescence and electron microscopy. It consists of a gold cluster compound that is visualized by electron microscopy and a covalently attached fluorophore that is visualized by fluorescence microscopy. FluoroNanogold has been an extremely useful labeling reagent in correlative microscopy studies. In this report, we present an overview of research using this unique probe. PMID- 26884820 TI - Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study. AB - Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID- 26884821 TI - Biological effects of RNAi targeted inhibiting Tiam1 gene expression on cholangiocarcinoma cells. AB - OBJECTIVE: To investigate the characteristics of Tiam1 gene expression in human cholangiocarcinoma tissues and benign bile duct tissues, and to analyze the correlations between Tiam1 gene expression and the degree of tumor differentiation, invasive and metastatic abilities. To explore the effect of targeted inhibiting Tiam1 gene expression on proliferation and migration activity of human cholangiocarcinoma cells. METHODS: Expression of Tiam1 in 83 cases of cholangiocarcinoma tissues and 25 cases of benign bile tissues was detected using immunohistochemistry. The clinical data of patients with cholangiocarcinoma were collected. The correlations between Tiam1 gene expression and the clinicopathologic features in patients with cholangiocarcinoma were analyzed. The human cholangiocarcinoma RBE cells were divided into 3 groups. Cells in experimental group and control group were respectively transfected with Tiam1 shRNA lentiviral vectors and negative shRNA lentiviral control vectors. Cells in blank group received no treatment. Real-time PCR endogenesis was used to verify Tiam1 gene expression. Cell cycle experiments and MTT assay were used to measure cell proliferation activity. Transwell test was used to detect cell migration activity. RESULTS: The negative rate Tiam1 protein expression in cholangiocarcinoma tissues was significantly higher than that in benign bile tissues (P<0.001). Tiam1 protein expression in cholangiocarcinoma tissues had correlations with cholangiocarcinoma differentiation degree, TNM stage and lymph node metastasis (P<0.05), and had no significant correlations with gender, age and distant metastasis (P>0.05). Real-time PCR detection indicated that Tiam1 expression of experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that Tiam1 shRNA was effective on Tiam1 gene silencing in RBE cells. Cell cycle experiment showed that the percentage of S phase in cell cycle in experimental group was lower than that in control group and blank group (P<0.05), demonstrating that after the down regulation of Tiam1 gene expression, the speed of cell proliferation was inhibited. MTT assay results showed that the total growth speed in experimental group was significantly lower than that in control group and blank group (P<0.05), indicating that the proliferation activity of cholangiocarcinoma cells was inhibited after targeted inhibition of Tiam1 gene expression. Transwell detection results showed that the metastasis rate in experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that targeted inhibition of Tiam1 gene expression could significantly inhibit migration ability of RBE cells. CONCLUSION: Tiam1 expression significantly increased in cholangiocarcinoma tissues, and increased along with the degree of malignancy of cholangiocarcinoma. Targeted silencing Tiam1 expression could inhibit proliferation and migration activity of cholangiocarcinoma cells. PMID- 26884822 TI - MiR-30a regulates the atrial fibrillation-induced myocardial fibrosis by targeting snail 1. AB - OBJECTIVE: Our study aims at assessing the association between miR-30a along with its target gene snail 1 and atrial fibrillation (AF)-induced myocardial fibrosis. METHODS: Ang II was used to up-regulate cardiac fibroblasts fibrosis in vitro, and then the cardiac fibroblasts were divided into the mimics group (mimics miR 30a), inhibitors group (inhibitors miR-30a), NC group (transfected miR-30a, negative control) and blank control group (non-transfected cells). Two-group (sham operated group and rapid pacing group) AF rabbit models were constructed according to whether rapid pacing was presented in the subject. Then the establishment of rabbit models was examined using histopathology after Masson staining. The mRNA and protein expression levels of snail 1 and periostin in cardiac fibroblasts and myocardial tissues were detected using the method of RT PCR and Western blot, respectively. RESULTS: In vitro, our experiment showed that overexpression of miR-30a in cardiac fibroblasts contribute to a significant decrease in the average expression level of snail 1 and periostin (P < 0.05) whereas inhibition of miR-30a significantly increased the average expression level of snail 1 and periostin (P < 0.05). In vivo, the average expression level of miR-30a significantly decreased in myocardial tissues with an increased degree of myocardial fibrosis, while the snail 1 and periostin expression level significantly increased during a certain period of time (P < 0.05). CONCLUSION: Our results suggest that miR-30a target snail 1 protein may be related to AF induced myocardial fibrosis. The average expression levels of snail 1 increased significantly in both myocardial cells and tissues, while miR-30a could inhibit the expression of snail 1. Thus, we speculate that miR-30a and snail 1 may be potential therapeutic targets for curing AF-induced myocardial fibrosis. PMID- 26884823 TI - Exogenous spermine ameliorates high glucose-induced cardiomyocytic apoptosis via decreasing reactive oxygen species accumulation through inhibiting p38/JNK and JAK2 pathways. AB - Reactive oxygen species (ROS) generation has been suggested to play a vital role in the initiation and progression of diabetic cardiomyopathy, a major complication of diabetes mellitus. Recent studies reveal that spermine possesses proliferative, antiaging and antioxidative properties. Thus, we hypothesized that spermine could decrease apoptosis via suppressing ROS accumulation induced by high glucose (HG) in cardiomyocytes. Cultured neonatal rat ventricle cardiomyocytes were treated with normal glucose (NG) (5 mM) or HG (25 mM) in the presence or absence of spermine for 48 h. The cell activity, apoptosis, ROS production, T-SOD and GSH activities, MDA content and GSSG level were assessed. The results showed that HG induced lipid peroxidation and the increase of intracellular ROS formation and apoptosis in primary cardiomyocytes. Spermine could obviously improve the above-mentioned changes. Western blot analysis revealed that spermine markedly inhibited HG-induced the phosphorylation of p38/JNK MAPKs and JAK2. Moreover, spermine had better antioxidative and anti apoptotic effects than N-acetyl-L-cysteine (NAC). Taken together, the present data suggested that spermine could suppress ROS accumulation to decrease cardiomyocytes apoptosis in HG condition, which may be attributed to the inhibition of p38/JNK and JAK2 activation and its natural antioxidative property. Our findings may highlight a new therapeutic intervention for the prevention of diabetic cardiomyopathy. PMID- 26884824 TI - Relationship between the gene polymorphisms of kallikrein-kinin system and Alzheimer's disease in a Hunan Han Chinese population. AB - This study aimed to determine the connection between polymorphisms of kallikrein kinin system including KLK1 (rs5516), KNG1 (rs710446, rs2304456) and ACE (rs4291, rs4309, rs4343) and late-onset Alzheimer's disease (LOAD). The research was conducted as a case-control study, comprising 201 AD patients in the AD group, and 257 healthy subjects as the control group. PCR amplification and matrix assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) were used to detect the six polymorphisms (rs5516 in KLK1; rs710446, rs2304456 in KNG1; rs4291, rs4309, rs4343 in ACE) from both groups. No statistically significant difference was found between the genotype and allelotype distributions of rs5516, rs710446, rs2304456, rs4291 and rs4343 (P>0.05). The differences between the genotype and allelotype distributions of the rs4309 were statistically significant (P<0.05). Haplotype analysis confirmed the existence of three haplotypes (AG, AT, GT) composed of rs710446/rs2304456, and six haplotypes (ATA, ACA, TCA, TCG, TTA, TTG) composed of rs4291/rs4309/rs4343, among which the distribution of ATA, ACA, TCA between the two groups was statistically significant difference (P<0.05). Our study showed that the polymorphisms of rs5516, rs710446, rs2304456, rs4291 and rs4343 is not related to the incidence of LOAD. The polymorphisms of rs4309 may be related to LOAD, as well as ATA, ACA, and TCA haplotype composed of rs4291/rs4309/rs4343. PMID- 26884825 TI - Hydrogen peroxide-induced apoptosis in human gingival fibroblasts. AB - In the process of bleaching vital, discolored teeth, low concentrations of hydrogen peroxide (H2O2) are effective alternatives to heat-activated 30% H2O2. However, interest has been expressed in the assessment of pathological effects of long-term exposure to bleaching agents such as irritation and ulceration of the gingival or other soft tissues. The aim of the present study was to determine the effect of hydrogen peroxide on apoptosis in human gingival fibroblasts (HGF). Cytochrome c, Bcl-2, Bax, Bid and caspase-3 protein expression were detected by Western blotting. HGF cell apoptosis induced by H2O2 was both dose and time dependent. The addition of H2O2 resulted in the release of cytochrome c to the cytosol, and an increase of Caspase-3 cleavage. Data suggest that oxidative stress-induced apoptosis in HGF is intrinsic pathway involved the release of apoptotic signal from mitochondria. PMID- 26884826 TI - Changes in focal adhesion kinase expression in rats with collagen-induced arthritis and efficacy of intervention with disease modifying anti-rheumatic drugs alone or in combination. AB - Focal adhesion kinase (FAK) is known to promote the proliferation, migration and survival of synovial cells and plays an important role in the occurrence, development and pathological process of rheumatoid arthritis (RA). The aim of the present study was to observe FAK changes in synovial cells of rats with collagen induced arthritis (CIA) and after intervention with disease modifying anti rheumatic drugs (DMARDs) alone or in combination in a CIA female SD rat model induced by collagen type II. The rats were randomized to 8 groups: normal control group, CIA model control group, methotrexate (MTX, 0.9 mg/kg/w) group, cyclophosphamide (CTX, 24 mg/kg/3 w) group, leflunomide (LEF, 1.2 mg/kg/d) group, MTX + CTX group, LEF + CTX group, and MTX + LEF group. They were intervened with DMARDs alone or in combination for six weeks. The experiment lasted a total of 9 weeks in vivo. Articular inflammation was measured during the process of drug intervention in terms of the degree of swelling degree in the right hind foot using a venire caliper. All animals were sacrificed by breaking the neck after 9 weeks. Then, the ankle was fixed, decalcified, embedded, and HE stained, and prepared into slices to observe pathological changes in the synovial tissue. FAK expression in synovial cells was assayed by immunohistochemistry and the mean optical density (OD) value was measured using the HPIAS-2000 image analysis system. It was found that FAK expression was negative in normal control group, positive in CIA model control group, and decreased in the three DMARD combination treatment groups significantly as compared with that in the three single-drug groups (P < 0.05). FAK expression in LEF + CTX group or MTX + CTX group decreased more significantly than that in MTX + LEF group (P < 0.05), and there was no statistically significant difference between LEF + CTX and MTX + CTX groups. The arthritis index and pathological change in the synovial tissue in LEF + CTX group or MTX + CTX group were improved more significantly than those in MTX + LEF group or single-drug groups. Our results showed that FAK expression was positive in CIA rats, indicating that it played an important role in the pathogenesis of RA, and that intervention with DMARDs could reduce the FAK expression in synovial cells of CIA rats. We hope these findings would contribute to the treatment of RA and other rheumatic diseases by reducing adhesion, proliferation and migration of synovial cells and inhibiting the over-expression of FAK. PMID- 26884828 TI - Molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos. AB - OBJECTIVE: To investigate the molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos. METHODS: SD female rats were mated with male rats in a 1:1 mating scheme. Thirty pregnant female rats were randomly divided into three groups: the control group receiving a normal diet, the model group receiving a vitamin A-deficient diet, and the treatment group receiving a vitamin A-deficient diet supplemented with pcDNA-Hoxd13. The expression of Hoxd13 mRNA and protein in normal embryonic tissue and congenital malformations was determined by RT-PCR and Western blot analysis. At day 20, rats were dissected, and the fetal weight, body and tail length, and the number of live births, absorbed fetus, and stillbirth in each group were recorded. Wnt and Slim1 expression was detected by RT-PCR and Western blot analysis. beta-catenin and c myc expression was also quantified by Western blot analysis. RESULTS: The expression of Hoxd13 mRNA and protein in congenital malformations was significantly lower compared with normal embryonic tissue (P<0.01). The administration of exogenous Hoxd13 in the treatment group markedly increased the fetal weight, body and tail length (P<0.05), improved the embryonic survival rate, and reduced the embryonic resorption rate and stillbirth rate (P<0.05). Exogenous Hoxd13 markedly promoted the expression of Wnt2, Wnt5a, Wnt7b and Slim1 protein and mRNA (P<0.01), and the expression of beta-catenin and c-myc protein in congenital malformations (P<0.01). CONCLUSION: Hoxd13 expression was decreased in rat embryos with congenital malformations. The administration of exogenous Hoxd13 alleviated fetal malformation probably through stimulation of Slim1 expression and Wnt/beta-catenin signaling pathway. PMID- 26884827 TI - Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement. AB - Deguelin, the main components from Mundulea sericea, was reported to suppress the growth of various cancer cells. However, the effect of Deguelin on tumor cell invasion and metastasis and its mechanism still unclear so far. In this study, we investigated the effects of Deguelin on the cell invasion in human lung cancer A549 and H460 cells. Our results demonstrate that Deguelin can significantly inhibited cell proliferation, cell migration and cell invasion. Moreover, Deguelin could also affected reorganization of the actin cytoskeleton and decreased filopodia and lamellipodia formation. Furthermore, deguelin-treated tumors showed decreased the tumor metastasis related genes such as CD44, MMP2 and MMP9 at protein and mRNA levels and the content of CEA, SCC, NSE, CYFAR21-1. In addition, Deguelin down-regulated protein expression of Rac1 and Rock1, which are impotent in actin cytoskeleton rearrangements and cell motility. Together, our results suggest that Deguelin inhibit tumor growth and metastasis of lung cancer cells and might be a candidate compound for curing lung cancer. PMID- 26884829 TI - IGFBP-3 may trigger osteoarthritis by inducing apoptosis of chondrocytes through Nur77 translocation. AB - Osteoarthritis is not an uncommon disease worldwide and it is characterized by chondrocytes apoptosis in articular cartilages. Previous researches had discovered that insulin-like growth factor binding protein-3 (IGFBP-3) was abundant inside the osteoarthritic cartilages and the more IGFBP-3, the worse of osteoarthritis. However, there is still little knowledge of the association between the onset of osteoarthritis and the yield of IGFBP-3 in cartilages. In consideration of the apoptotic effect of IGFBP-3 on other types of cells, we had hypothesized that IGFBP-3 may induce the chondrocytes apoptosis, which was highly considered as the origin of the osteoarthritis. Exposing the cultured chondrocytes to exogenous recombinant IGFBP-3, we were able to observed the apoptotic chondrocytes under microscope and figured out an increased proportion (P<0.05) of them by both CCK-8 assay and flow cytometry. Under laser confocal microscope, we also found that the apoptosis of chondrocytes induced by IGFBP-3 were committed to the nucleus-mitochondria translocation of Nur77, which is nuclear protein, and this phenomena was similar as the one described in malignant cells only. In conclusion, our work suggested that IGFBP-3 may trigger osteoarthritis by inducing the chondrocytes apoptotic through nucleus mitochondria translocation of Nur77. PMID- 26884830 TI - microRNA-451 inhibited cell proliferation, migration and invasion through regulation of MIF in renal cell carcinoma. AB - The expression and functions of microRNA-451 have been studied in many human cancers. However, up to date, there is no study of microRNA-451 in renal cell carcinoma. In the present study, we aimed to investigate the expression, biological functions and molecular mechanisms of microRNA-451 in renal cell carcinoma. microRNA-451 expression level in renal cell carcinoma tissues and cell lines was measured using quantitative Real-time PCR. By using CCK8 assay, cell migration and invasion assay, we explored the functions of microRNA-451 in renal cell carcinoma. Dual-Luciferase report assay, quantitative Real-time PCR and western blot were performed to explore the molecular mechanisms of microRNA-451 functions in renal cell carcinoma. Functional assays were also performed to explore the effects of endogenous MIF in renal cell carcinoma. In this study, we showed for the first time that microRNA-451 was significantly down-regulated in renal cell carcinomas tissues and cell lines. microRNA-451 expression level was correlated with histological grade and lymph node metastasis. In addition, microRNA-451 inhibited proliferation, migration and invasion of renal cell carcinomas cells. Moreover, MIF was identified as a target of microRNA-451, and down-regulation of MIF could mimic the suppressive functions of microRNA-451 in renal cell carcinomas, suggesting that microRNA-451 might be a novel therapeutic strategy for the treatment of renal cell carcinomas. PMID- 26884831 TI - Lysosomal integral membrane protein Sidt2 plays a vital role in insulin secretion. AB - Abnormal insulin secretion results in impaired glucose tolerance and is one of the causal factors in the etiology of type 2 diabetes mellitus. Sidt2, a lysosomal integral membrane protein, plays a critical role in insulin secretion. Here, we further investigate its regulation in insulin secretion. We show that Sidt2(-/-) mice exhibit weight loss, decreased postnatal survival rate with aging, increased fasting glucose and impaired glucose tolerance. After loading high levels of glucose in their diet, Sidt2(-/-) mice produce notably lower insulin levels at the first-phase secretion compared with Sidt2(+/+) mice. Consistent with the in vivo study, INS-1 cells treated with Sidt2 siRNA produced less insulin when loaded with 16.7 mM of glucose. Only 2 of the 13 genes, synap1 and synap3 which encode soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins, showed significantly decreased expression in Sidt2(-/ ) mice. In conclusion, Sdit2 may play a vital role in the regulation of insulin secretion via two SNARE proteins synap1 and syanp3. PMID- 26884833 TI - Expression of CD11a in lymphocyte subpopulation in immune thrombocytopenia. AB - Recent research demonstrates that the underlying mechanism in immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important roles in autoimmune diseases. The purpose of this study was to investigate the expression of CD11a on lymphocytes and explore its possible role in ITP. The expression of CD11a on lymphocyte subpopulations (CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD4(-) T cells, CD4(+)Foxp3(+) T regulatory cells and CD19(+) B cells) were analyzed by flow cytometry. Specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). The mean fluorescence intensity of CD11a on CD3(+) T, CD3(+)CD4(-) T and CD19(+) B lymphocytes were increased in ITP patients compared to healthy controls. No significant difference of CD11a expression on CD3(+)CD4(+) T cells or CD4(+)Foxp3(+) T regulatory cells was found between ITP patients and controls. Our data indicates the possible role of CD11a in the pathogenesis of ITP. PMID- 26884834 TI - Withaferin A activates stress signalling proteins in high risk acute lymphoblastic leukemia. AB - Withaferin A, the principal bio-active component isolated from the Withaniasomnifera, has shown promising anti-leukemic activity in addition to anti invasive and anti-metastatic activity. The present study demonstrates the effect of withaferin A on the cell cycle status and the phosphorylation/activation of proteins involved in signal transduction in t(4;11) and non-t(4;11) acute lymphoblastic leukemia (ALL) cell lines after treatment with withaferin A. The cells after treatment with the vehicle or 25 MUM withaferin A for 1, 2, 4 and 8 h were examined using flow cytometric analysis. The results revealed that withaferin A treatment induced cell growth arrest at the S to G2/M phase transition of the cell cycle. Withaferin A treatment also induced the phosphorylation of stress signalling proteins, including the p38 mitogen activated protein kinase, the c-Jun N-terminal kinase, c-Jun, the heat shock protein 27 and protein kinase B within 0 to 16 h. These results were observed using multiplex technology and Western blotting analysis. Thus withaferin A induces stress response leading to cell death. Therefore, withaferin A can be a potent therapeutic agent for the treatment of high risk ALL with chromosomal translocation t(4;11). PMID- 26884832 TI - MiR-30a-5p suppresses cell growth and enhances apoptosis of hepatocellular carcinoma cells via targeting AEG-1. AB - BACKGROUND: MiR-30a-5p has been reported to play vital roles in the carcinogenesis and progression of various malignancies via different molecular mechanisms. However, the role and target genes of miR-30a-5p in hepatocellular carcinoma (HCC) remain still unclear. In silico analysis finds that there are complementary sequences between the 3'-untrasnlated region of astrocyte elevated gene 1 (AEG-1) and miR-30a-5p. Herein, we investigated the biological function of miR-30a-5p, as well as the potential molecular mechanism via targeting AEG-1 in HCC cells. MATERIALS AND METHODS: MiR-30a-5p inhibitor, miR-30a-5p mimic, AEG-1 siRNAs, as well as their negative controls were transfected into HCC cell lines HepG2, SMMC-7221, HepB3 and SNU449. Then, the in vitro influence and mechanism of miR-30a-5p on cell viability, proliferation, caspase-3/7 activity and apoptosis were studied, as assessed by different methods, including spectrophotometry, fluorimetry, fluorescence microscopy of Hoechst 33342/propidium iodide double chromatin staining, western blot and dual luciferase reporter assay, respectively. RESULTS: MiR-30a-5p mimic markedly inhibited cell growth, also induced caspase-3/7 activity and apoptosis in all four HCC cell lines tested. The strongest effect was observed in HepG2 and SMMC-7721 cells. However, this effect was slightly weaker than that of AEG-1 siRNAs. Transfection of miR-30a-5p mimic led to a markedly reduced AEG-1 protein level and further dual luciferase reporter assay confirmed that AEG-1 was one of the target genes of miR-30a-5p in HCC cells. CONCLUSIONS: MiR-30a-5p may play an essential role in the cell growth and apoptosis of HCC cells, partially via targeting AEG-1. PMID- 26884835 TI - siRNA-TMEM98 inhibits the invasion and migration of lung cancer cells. AB - Non-small cell lung cancer (NSCLC) is one of the most common human malignancies, which threatens people's life heavily. Recently, TMEM98 is supposed to be of great value for the discoveries of anti-tumor drugs. We attempt to explore the biological role of TMEM98 in the human lung carcinoma. Clinical lung cancer tissue and normal tissue were collected, and the mRNA expression of TMEM98 in cancer tissue was significantly higher than that in normal tissue. By real-time PCR and Western blot analysis of TMEM98 expression, human A549 and H460 cells were determined to carry out further investigations. By CCK8, it is found that siRNA-TMEM98 treatment effectively suppressed the proliferation of A549 and H460 cells. In addition, the invasion and migration of A549 and H460 cells were also inhibited by siRNA-TMEM98. We then studied the invasion and migration related proteins level by Western blot. From our result, the protein expression of MMP-2, MMP-9, RhoC and MTA1 were all regulated dramatically in siRNA-TMEM98 groups compared with the control and mock group. To conclude, our results indicated that siRNA-TMEM98 inhibited the invasion and migration of lung cancer cells, which can be considered as a novel target for NSCLC treatment. PMID- 26884836 TI - Losartan attenuated lipopolysaccharide-induced lung injury by suppression of lectin-like oxidized low-density lipoprotein receptor-1. AB - INTRODUCTION: Recent study has shown that renin-angiotensin system plays an important role in the development of acute lung injury (ALI) with high level of angiotensin II (AngII) generated form AngI catalyzed by angiotensin-converting enzyme. AngII plays a major effect mainly through AT1 receptor. Therefore, we speculate inhibition of AT1 receptor may possibly attenuate the lung injury. Losartan, an antagonist of AT1 receptor for angiotensin II, attenuated lung injury by alleviation of the inflammation response in ALI, but the mechanism of losartan in ALI still remains unclear. METHODS: Thirty male Sprague-Dawley rats were randomly divided into Control group, ALI group (LPS), and Losartan group (LPS + Losartan). Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis. The expressions of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), intercellular adhesion molecule-1 (ICAM-1) and caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT PCR) and western blotting. RESULTS: In ALI group, TNF-alpha and protein level in BALF, MPO activity in lung tissue, pulmonary edema and lung injury were significantly increased. Losartan significantly reduced LPS-induced increase in TNF-alpha and protein level in BALF, MPO activity, pulmonary edema and lung injury in LPS-induced lung injury. The mRNA and protein expression levels of LOX 1 were significantly decreased with the administration of losartan in LPS-induced lung injury. Also, losartan blocked the protein levels of caspase-3 and ICAM-1 mediated by LOX-1 in LPS-induced lung injury. CONCLUSIONS: Losartan attenuated lung injury by alleviation of the inflammation and cell apoptosis by inhibition of LOX-1 in LPS-induced lung injury. PMID- 26884837 TI - MiR-15b mediates liver cancer cells proliferation through targeting BCL-2. AB - The incidence and mortality of liver cancer increased year by year. Our country presents high incidence of liver cancer. MicroRNAs have tissue sensitivity as tumor biomarkers that play a role by promoting tumor growth as oncogenes or inhibit malignant cell growth as tumor suppressor genes. Studies showed that miR 15b abnormal expression in the tumor and can be treated as one of the tumor molecular markers. However, miR-15b expression and role in the liver cancer cells have not been elucidated. This study intended to explore the mechanism of miR-15b effect on liver cancer occurrence and development. Liver cancer cell line HepG2 was transfected with miR-15b mimic or inhibitor. Real-time PCR was applied to detect miR-15b expression. MTT was used to test cell proliferation. Transwell assay was performed to determine cell invasive ability. Real-time PCR and Western blot were used to detect BCL2 expression. MiR-15b mimic transfection promoted miR 15b overexpression and inhibited HepG2 cell proliferation significantly (P < 0.05). MiR-15b overexpression downregulated BCL2 mRNA and protein expression obviously (P < 0.05). On the contrary, miR-15b inhibitor transfection markedly reduced miR-15b expression in liver cancer cells (P < 0.05), promoted tumor cell proliferation, and increased BCL2 mRNA and protein expression. MiR-15b expression changes did not affect cell invasion (P > 0.05). MiR-15b can inhibit HepG2 cell proliferation and down-regulate BCL2 mRNA and protein expression. PMID- 26884838 TI - Curcumin improves bone microarchitecture in glucocorticoid-induced secondary osteoporosis mice through the activation of microRNA-365 via regulating MMP-9. AB - The present study aimed to investigate bone microarchitecture of the proximal tibia in glucocorticoid-induced osteoporosis (GIOP) mice, and the underlying molecular mechanisms of curcumin in DXM-induced osteoporosis were performed. DXM treated facilitated to induce hypercalciuria in mice, and curcumin-treated showed a decrease in urine calcium. Curcumin reversed DXM-induced bone resorption, including an increase in serum OCN and a decrease in bone resorption markers CTX and TRAP-5b. H&E staining showed the increased disconnections and separation in trabecular bone network as well as the reduction of trabecular thickness throughout the proximal metaphysis of tibia in GIOP group. Importantly, curcumin reversed DXM-induced trabecular deleterious effects and stimulated bone remodeling. The further evidence showed that curcumin supplement significantly decreased the TRAP-positive stained area and inhibited the activity of OPG/RANKL/RANK signaling in the GIOP mice. Moreover, bioinformatics analysis suggested that miR-365 was a regulator of MMP9. The levels of miR-365 were markedly suppressed; however, curcumin treatment could reverse the downregulation of miR-365 in the tibia of GIOP mice. Simultaneously, the results demonstrated that the mRNA and protein expression of MMP-9 were significantly increased in GIOP mice compared with that of the control group. Curcumin treatment could suppress the expression of MMP-9 in the tibia of GIOP mice. The present study demonstrated the protective effects of curcumin against bone deteriorations in the experimentally DIOP mice, and the underlying mechanism was mediated, at least partially, through the activation of microRNA-365 via suppressing MMP9. PMID- 26884839 TI - Simvastatin ameliorates renal lipidosis through the suppression of renal CXCL16 expression in mice with adriamycin-induced nephropathy. AB - AIMS: To investigate the roles of CXCL16 and ox-LDL in adriamycin (ADR)-induced nephropathy mice and to explore the mechanism of simvastatin on the renal protective effects of ADR nephropathy. METHODS: Fifteen male Balb/c mice were randomly divided into normal control (NC), ADR nephropathy and simvastatin treated ADR nephropathy (ADR-SIM) groups. ADR nephropathy was induced by a single intravenous injection of ADR into the tail vein. All mice were sacrificed at the end of the 7th week, with the blood, 24-h urine and kidneys collected. The levels of ox-LDL and total cholesterol in the serum, the serum CXCL16, ox-LDL and NF kappaB expression were detected. RESULTS: Compared with the NC group, the levels of serum total cholesterol and ox-LDL in the ADR and ADR-SIM groups were significantly higher, the level of serum albumin was significantly lower and the expression of CXCL16, ox-LDL and NF-kappaB in the renal tissue of ADR and ADR-SIM groups was significantly increased. Compared with the ADR group, the expressions of renal CXCL16, ox-LDL and NF-kappaB in the ADR-SIM group were significantly decreased. Levels of serum total cholesterol and ox-LDL were not significantly different between the two groups. CONCLUSIONS: Simvastatin exerts a protective effect on renal function and structure in mice with ADR nephropathy. The beneficial effects of simvastatin might be related to the decreasing expression of CXCL16 in glomerular podocytes followed by the decreasing endocytosis of ox LDL in podocytes and inhibition of NF-kappaB pathway activation. PMID- 26884840 TI - Kissing molars: report of three cases and new prospective on aetiopathogenetic theories. AB - Kissing molars (KMs) is an extremely rare condition of impacted third molars, pointed in the opposite direction in a single follicular space; it consists exactly in a full impacted of permanent molars which occurs only in the lower jaw. Actually, about less than thirty cases have been reported in scientific literatures. The aetiology and pathogenesis of this pathological double dental inclusion remain unknown; above all events that lead two molars to appear, as KMs remain mysterious. The association to metabolic connective diseases such as mucopolysaccharidosis was emphasized. KMs considered as an isolated event, may be associated to an abnormal position of the tooth-bud from lower permanent molars, or fourth supernumerary tooth (distomolar). Recently, hyperplastic dental follicle (HDF), with a down regulation of matrix metal-proteinases and up regulation of several genes of collagens, has been mentioned in association with KMs. In this paper, after having analyzed three new cases of KMs that have been treated, we report a new hypothesis. This last is based on the failure in the dental follicle's ability to initiate or continue properly resorption of the overlying alveolar bone, by many exogenous factors which may act on eruptive phase that would lead to its rotation with its contents coming out a pathological situation of KMs. The therapy of choice is related to the surgical removal of KMs through a double odontectomy with transalveolar method. Other treatments can be, eventually, orthodontic therapy of the impacted teeth and a radiological follow up without surgery. PMID- 26884842 TI - CCL21/CCR7 up-regulate vascular endothelial growth factor-D expression via ERK pathway in human non-small cell lung cancer cells. AB - Lymphangiogenesis has received considerable attention and become a new research hotspot of tumor metastasis. Recently, C-C chemokine receptor 7 (CCR7) is known to promote metastasis of non-small cell lung cancer (NSCLC) cells into lymph nodes. In this study, we investigated the relationship between CCL21/CCR7 and the lymphangiogenic factor vascular endothelial growth factor (VEGF)-D in human lung cancer cells and its impact on patients' prognosis. We found that CCL21/CCR7 increase the expression of VEGF-D in NSCLC Cell Lines through induced ERK1/2 and Akt phosphorylation. In addition, our study found that the expression levels of CCR7 and CCL21 were correlated with VEGF-D, lymphatic vessels density (LVD), clinical stages, lymph node metastasis, and patient Survival in 90 human non small cell lung cancer (NSCLC) specimens. Taken together, our results provide evidence that CCL21/CCR7 induce VEGF-D up-regulation and promote lymphangiogenesis via ERK/Akt pathway in lung cancer. PMID- 26884841 TI - Exosomes mediated pentose phosphate pathway in ovarian cancer metastasis: a proteomics analysis. AB - Epithelial ovarian cancer is the most lethal gynecological malignancies for readily metastasis. Exosomes have played an influential role in carcinogenicity and cancer progression. Our aim is to discover exosome-related mechanisms in ovarian cancer progress and explore potential diagnostic biomarkers and therapeutic targets of ovarian cancer. We initially presented the proteomic profiles of exosomes derived from two late-stage ovarian cell lines, OVCA429 and HO8910PM. A total of 2940 exosomal proteins were recorded by MS. FunRich appropriately processed these exosomal proteins, manifesting some superiority in contrast to Blast2go. Moreover, we demonstrated the pentose phosphate pathway was a dominant mechanism in exosome mediated intracellular communication. Glucose-6 phosphate dehydrogenase, transketolase and transaldolase 1, three key enzymes regulated pentose phosphate pathway, were all marked in the same exosomal parts of proteins between two ovarian cell lines. Moreover, these key proteins might become diagnostic, prognostic biomarkers and therapeutic targets of ovarian cancer. PMID- 26884843 TI - Protective effects of adipose-derived stem cells secretome on human dermal fibroblasts from ageing damages. AB - BACKGROUND: Combined effects of intrinsic and extrinsic ageing factors on skin tissue and the therapies have been rarely studied before. ADSCs have gained popularity in anti-ageing field, which may provide promising methods to fight against skin ageing. OBJECTIVE: To find out the fate of HDFs exposed to intrinsic or extrinsic ageing factors or both of them and further examine the impacts of ADSC-CM on the damaged HDFs. METHODS: We irradiated HDFs with UVB at different senescent levels, and then treated them with ADSC-CM. After 48 h, we detected cellular proliferative activity, morphology, SA-beta-Gal expression, apoptosis, mRNA expression of collagen I, collagen III and elastin. RESULTS: Intrinsic ageing factors inhibited cellular proliferation, increased senescent ratio and reduced mRNA expression of collagen I, collagen III and elastin, so did UVB, except for its induction of elastin mRNA expression. Furthermore, ADSC-CM treatment can slightly or significantly improve cellular proliferative activity and restore functions both in irradiated and non-irradiated HDFs. Besides, ADSC CM treatment decreased cellular apoptosis and senescence induced by UVB but had no obvious effect on cellular senescence induced by intrinsic ageing factors. The results were similar in three generations of HDFs, yet in different degrees. CONCLUSIONS: The results suggest that ADSCs secretome protect HDFs from ageing damages but with some limitations. PMID- 26884845 TI - Role of Bcl-2 and its associated miRNAs in vasculogenic mimicry of hepatocellular carcinoma. AB - OBJECTIVE: An investigation of the role of the anti-apoptotic protein Bcl-2 and its associated miRNAs in vasculogenic mimicry (VM) in hepatocellular carcinoma. METHODS: The Bcl-2 expression plasmid was constructed for transfection into the hepatocellular carcinoma cell line HepG2. Changes in the expression profiles of the miRNAs induced by Bcl-2 overexpression and their relationships with vasculogenic mimicry were analysed. Real-time PCR was performed in frozen tissue specimens from 42 cases of hepatocellular carcinoma to analyse the relationship between Bcl-2 and miR-27a; Immunohistochemical staining was performed in paraffin embedded tissue samples from 97 cases of hepatocellular carcinoma to analyse the relationship between Bcl-2 expression and the expression of vasculogenic mimicry (VM) related molecules VEGF and HIF1A, which were target genes of the Bcl-2 related miRNAs. RESULTS: Overexpression of Bcl-2 results in a significant change in the expression of a wide range of miRNAs, and the target genes of these miRNAs are composed of various vasculogenic mimicry related genes; Bcl-2 expression was positively correlated with the expression of the miRNA target genes VEGF and HIF1A. The expression of VEGF and HIF1A was significantly and positively correlated with VM and poor prognosis of patients. CONCLUSION: Bcl-2 may play a role in vasculogenic mimicry through miRNAs by targeting angiogenesis associated genes. PMID- 26884844 TI - Elevation of AQP4 and selective cytokines in experimental autoimmune encephalitis mice provides some potential biomarkers in optic neuritis and demyelinating diseases. AB - Idiopathic optic neuritis (ION) is an inflammation of the optic nerve that may result in a complete or partial loss of vision. ION is usually due to the immune attack of the myelin sheath covering the optic nerve. ION acts frequently as the first symptoms of multiple sclerosis (MS) and neuromyelitis optica (NMO), or other inflammatory demyelinating disorders. The pathogenic progression of ION remains unclear. Experimental autoimmune encephalitis (EAE) is a commonly used model of idiopathic inflammatory demyelinating disorders (IIDDs); the optic nerve is affected in EAE as well. The specific mediators of demyelination in optic neuritis are unknown. Recent studies have indicated what T-cell activation in peripheral blood is associated with optic neuritis pathogenesis. The object of the present study was to determine whether certain cytokines (IL-6, IL-17A, and IL-23) and AQP4 contribute to the demyelinating process using EAE model. We have found that IL-6R, AQP4 and IL-23R are significantly increased in mRNA and protein levels in optic nerves in EAE mice compared to control mice; serum AQP4, IL-6, IL 17A, IL-23 are increased whereas transforming growth factor beta (TGF-beta) is decreased in EAE mice. These results suggest that AQP4 and selective cytokines in serum are associated with ION pathogenesis in the animal model, and these results shine light for future clinical diagnosis as potential biomarkers in ION patients. PMID- 26884846 TI - Neuroprotective effect of functionalized multi-walled carbon nanotubes on spinal cord injury in rats. AB - Traumatic injuries to the brain and spinal cord affect a large percentage of the world's population. However, there are currently no effective treatments for these central nervous system (CNS) injuries. In our study, we evaluated the neuroprotective role of functionalized multi-walled carbon nanotubes (MWCNTs) carrying brain derived neurotrophic factor (BNDF), nogo-66 receptor (NgR) and Ras homolog gene family member A (RhoA) in spinal cord injury (SCI). Our results showed that transfection into rat cortical neurons with BDNF-DNA significantly elevated the expression of BDNF both in vitro and in vivo. Meanwhile, transfection with NgR-siRNA and RhoA-siRNA resulted in an obvious down-regulation of NgR and RhoA in neuron cells and in injured spinal cords. In addition, the functionalized MWCNTs carrying BDNF-DNA, NgR-siRNA and RhoA-siRNA exhibited remarkable therapeutic effects on injured spinal cord. Taken together, our study demonstrates that functionalized MWCNTs have a potential therapeutic application on repair and regeneration of the CNS. PMID- 26884847 TI - Mechanism of bile acid-regulated glucose and lipid metabolism in duodenal-jejunal bypass. AB - Bile acid plays an important role in regulating blood glucose, lipid and energy metabolism. The present study was implemented to determine the effect of duodenal jejunal bypass (DJB) on FXR, TGR-5expression in terminal ileum and its bile acid related mechanism on glucose and lipid metabolism. Immunohistochemistry was used to detect relative gene or protein expression in liver and intestine. Firstly, we found that expression of FXR in liver and terminal ileum of DJB group was significantly higher than that in S-DJB group (P<0.05). In addition, DJB dramatically increased the activation of TGR-5 in the liver of rats. Furthermore, PEPCK, G6Pase, FBPase 1 and GLP-1 were up-regulated by DJB. In conclusion, these results showed that bile acid ameliorated glucose and lipid metabolism through bile acid-FXR and bile acid- TGR-5 signaling pathway. PMID- 26884849 TI - Effects of CASP5 gene overexpression on angiogenesis of HMEC-1 cells. AB - OBJECTIVES: The efficacy of gene overexpression of CASP5, a caspase family member, in angiogenesis in vitro and its mechanisms were clarified. METHODS: Human full-length CASP5 gene was delivered into human microvascular endothelial HMEC-1 cells by recombinant lentivirus. The infection was estimated by green fluorescent protein. MTT method was used to analyze the efficacy of gene overexpression in cell proliferation ability, and Matrigel was used to estimate its effects in angiogenesis ability of cells. Meanwhile, Western blot was used to analyze the effects of CASP5 gene overexpression on the expression levels of angpt-1, angpt-2, Tie2 and VEGF-1 in the cells, which were signaling pathway factors related to angiogenesis. RESULTS: Recombinant lentivirus containing human full-length CASP5 gene was packed and purified successfully, with virus titer of 1*10(8) TU/ml. The recombinant lentivirus was used to infect HMEC-1 cells with MOI of 1, leading to a cell infection rate of 100%. There were no significant effects of CASP5 gene overexpression on both cell proliferation ability and the expression level of angpt-1. Meanwhile, expressions of angpt-2 and VEGF-1 were both enhanced, while Tie2 expression was inhibited. Results indicated that CASP5 gene overexpression promoted angiogenesis of HMEC-1 cells. CONCLUSION: CASP5 gene overexpression significantly promoted angiogenesis ability of HMEC-1 cells, which was probably achieved by inhibiting angpt-1/Tie2 and promoting VEGF-1 signal pathway. PMID- 26884848 TI - Full-length spleen tyrosine kinase inhibits the invasion and metastasis of human laryngeal squamous cell carcinoma. AB - OBJECTIVE: This study aimed to investigate correlation between full-length spleen tyrosine kinase [SYK (L)] expression and clinical characteristics of laryngeal squamous cell carcinoma (LSCC), and explore effects of SYK (L) on invasion and metastasis of LSCC. METHODS: The human laryngeal cancer Hep-2 cells with low SYK (L) expression were transfected with pIRES2-EGFP-SYK (L) vector and empty vector pIRES2-EGFP to generate Hep-2-SYK (L) cells and Hep-2-neo cells. The cell invasion and migration abilities were determined. RESULTS: The SYK (L) positive expression rate in LSCC tissues was significantly lower than in vocal cord dysplasia tissues and normal laryngeal tissues (P < 0.05). There was a significant correlation between SYK (L) expression and LSCC T stage, histopathological grade and lymph node metastasis (P < 0.05). mRNA expression of SYK (L) in Hep-2-SYK (L) cells was significantly higher than in Hep-2-neo cells and Hep-2 cells (P < 0.01). The protein expression of SYK (L) in Hep-2-SYK (L) cells was markedly higher than in Hep-2-neo cells and Hep-2 cells (P < 0.01). The number of invasive cells was significantly lower in Hep-2-SYK (L) group than in Hep-2-neo group and Hep-2 group (P < 0.01). The average number of migrating cells in Hep-2-SYK (L) group also markedly reduced as compared to Hep-2-neo group and Hep-2 group (P < 0.01). CONCLUSION: The SYK (L) expression was down-regulated in LSCC, which was closely correlated with cancer growth and lymph node metastasis. SYK (L) up-regulation was able to inhibit the invasion and metastasis of LSCC, therefore suppressing tumor development. Thus, SYK (L) may be a potential target for the LSCC treatment. PMID- 26884850 TI - Expression of TAK1/TAB1 expression in non-small cell lung carcinoma and adjacent normal tissues and their clinical significance. AB - The purpose of this study was to investigate the expression of transforming growth factor beta-activated kinase 1 (TAK1) and its activation ligand, TAK1 binding protein 1 (TAB1), in non-small cell lung carcinoma (NSCLC) and adjacent normal tissues and to analyze the relevance between TAK1 and TAB1 protein expression and the pathological features of NSCLC patients. Surgical resection NSCLC specimens were collected from 74 patients undergoing surgery in our hospital from September 2003 to July 2008; tumor-adjacent normal tissue specimens were collected as controls. All cases were pathologically confirmed after surgery, and pathological data were complete for all patients. The expression of TAK1/TAB1 proteins in NSCLC and adjacent cancer tissues was detected by immunohistochemical analysis. The correlation between TAK1/TAB1 protein expression and the clinicopathological features and outcome of NSCLC was assessed. The positive expression ratio of TAK1 in NSCLC tissue was 63.5%, which was significantly higher than that in tumor-adjacent normal tissue (31.1%). The positive expression ratio of TAB1 in NSCLC tissue was 51.4%, which was significantly higher than that in tumor-adjacent normal tissue (24.3%). Further analysis showed that positive protein expression of TAK1 and TAB1 was unrelated to patient gender, age, tumor size, degree of differentiation, and history of smoking (P>0.05) but was significantly related to clinical stage and lymph node metastasis (P<0.05). Additionally, the expression of TAK1 as well as TAB1 was negatively related to NSCLC patient prognosis, and patients with positive protein expression had a significantly lower 5-year survival rate than those with negative protein expression (P<0.05). TAK1/TAB1 expression in NSCLC tissue is significantly increased and closely associated with patient clinical prognosis. These two proteins are likely to become new therapeutic targets for the treatment of NSCLC. PMID- 26884851 TI - Regulator role of HPV E7 protein on miR-21 expression in cervical carcinoma cells and its functional implication. AB - Cervical cancer is the second leading malignant tumor in women. Human papillomavirus 16 (HPV16) is one risk factor for cervical cancer, with its expressed E7 protein can facilitate the transformation of cervical epithelial cells. MicroRNA-21 (miR-21) is one important tumor growth regulatory factor involving in angiogenesis, tumor invasion and metastasis. This study thus aimed to investigate the role of high-risk HPV16 E7 protein in regulating miR-21 expression in cervical carcinoma and its related functions. Hela cells were transfected with pcDNA-HPV16 E7 expressing vectors. The expression level of E7 was determined by Western blotting, while miR-21 level was quantified by real time PCR. The alternation of tumor cell proliferation is determined by transfecting miR-21 inhibitor into E7-overexpressing Hela cells. Cell apoptosis was studied by caspase-3 assay, while cell invasion was illustrated in Transwell chamber. The overexpression of HPV E7 protein facilitated the expression of miR 21, which potentiated Hela cell proliferation and invasion. The inhibition of miR 21 in E7-overexpressin Hela cells can inhibit both proliferation and invasion, but without significant effects on caspase-3 activity. HPV16 E7 protein can up regulate host miR-21 expression, thus elevating cervical carcinoma cell growth, proliferation and invasion. Therefore, E7 protein is one critical factor in occurrence and progression of cervical carcinoma. PMID- 26884852 TI - Low cytoplasmic and nuclear KPNA2 expression in radiotherapy-treated head and neck squamous cell cancer is associated with an adverse outcome. AB - BACKGROUND: KPNA2 has effects on carcinogenesis, cell differentiation and transcriptional regulation. KPNA2 has been linked to DNA damage repair by its role to import the DNA double strand break repair complex MRN into the nucleus. The aim of our study was to evaluate the prognostic value of KPNA2 expression in both cytoplasmic and nuclear location in patients with HNSCC treated with radio(chemo)therapy. MATERIAL AND METHODS: 225 patients with HNSCC treated with neoadjuvant, definitive or adjuvant radio(chemo)therapy were included. Immunohistochemical staining was performed on tissue micro arrays to evaluate nuclear and cytoplasmic KPNA2 expression. RESULTS: The median fraction of tumor cells with nuclear KPNA2 expression was 15%. 47% of tumor samples showed positive cytoplasmic staining. Patients with low nuclear as well as negative cytoplasmic expression tended to have an unfavorable prognosis. There was no correlation between nuclear and cytoplasmic KPNA2 expression. Low nuclear combined with negative cytoplasmic KPNA2 had a clearly unfavorable prognostic effect in local failure-free survival (P=0.014), metastasis-free survival (P=0.001) and no evidence of disease (P=0.008). A combination of low nuclear/negative cytoplasmic with high nuclear/high cytoplasmic KPNA2 expression was prognostically unfavorable with regard to tumor specific survival (P=0.021) and to a lower extent to overall survival (P=0.18). In multivariate analysis low nuclear/negative cytoplasmic versus any high KPNA2 (P=0.008) and T-category (P=0.002) proved as independent prognostic variables. CONCLUSION: The combination of nuclear and cytoplasmic KPNA2 expression is a potential excellent prognostic parameter in HNSCC treated with radio(chemo)therapy. PMID- 26884854 TI - Quantitative proteomic analysis identifies new effectors of FOXM1 involved in breast cancer cell migration. AB - The Forkhead Box M1 (FOXM1) transcription factor plays important roles in tumorigenesis and tumor metastasis in multiple human carcinomas. However, the underlying mechanisms for FOXM1 function remain to be classified. In the present study, we employed quantitative proteomic approach to search new downstream targets of FOXM1 in breast cancer MDA-MB-231 cells. A total of 4125 proteins were identified and quantified by label-free quantitation, of which 318 proteins were significantly changed (with P-value <0.05) between FOXM1 knockdown cells and control cells. Among them, three proteins ACSL4, CGGBP1 and PGRMC2 were significantly downregulated with FOXM1 reduction by western blot analysis. Further functional assays revealed that knockdown of the three proteins in MDA-MB 231 cells attenuated the ability of cell migration, consistent with the phenotype of FOXM1 knockdown. These results suggest that new potential downstream effectors of FOXM1 were identified by proteomic approach, and may provide new potential therapeutic targets in breast cancer. PMID- 26884853 TI - Prevalence and clinicopathologic features of CD30-positive de novo diffuse large B-cell lymphoma in Chinese patients: a retrospective study of 232 cases. AB - Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that great efforts had been made in to build up molecular and immunophenotypic subgroups that could relatively accurate indicate prognosis and give clue to therapy. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, especially in Asian patients. Here, we studied 232 cases of de novo DLBCL in East China to investigate the prevalence and clinicopathological features of CD30-positive DLBCL using a panel of immunohistochemical markers. Applying a >0% threshold, CD30 was expressed in approximately 12% patients with Epstein-Barr virus (EBV) negative DLBCL, affecting younger people and showing a lower frequency of BCL2 expression and MYC/BCL2 co-expression. Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on BCL2+ DLBCL or DLBCL with MYC/BCL2 co-expression. Moreover, CD30 could express in CD5+ DLBCL. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes in a Chinese population. Further studies with larger samples should be performed to investigate the function of CD30 expression in BCL2+ DLBCLs, DLBCLs with MYC/BCL2 co-expression, and CD5+ DLBCLs, and to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy. PMID- 26884855 TI - 14-3-3zeta up-regulates hypoxia-inducible factor-1alpha in hepatocellular carcinoma via activation of PI3K/Akt/NF-kB signal transduction pathway. AB - 14-3-3zeta protein, a member of 14-3-3 family, plays important roles in multiple cellular processes. Our previous study showed that 14-3-3zeta could bind to regulate the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), which is induced by hypoxia and a crucial factor for induction of tumor metastasis. Moreover, we also have confirmed the response of 14-3-3zeta to hypoxia in our unpublished data as well. Thus, in the present study, we attempted to reveal that whether the regulation effect of 14-3-3zeta on HIF-1alpha functioned in a similar pattern as hypoxia. Stable regulation of 14-3-3zeta in human HCC cell line SMMC 772 and HCC-LM3 was achieved. The regulation of 14-3-3zeta on HIF-1alpha mRNA transcription was evaluated by luciferase activity assay and quantitative real time PCR (qPCR). The effect of 14-3-3zeta on the production of HIF-1alpha and pathways determining HIF-1alpha's response to hypoxia was assessed using western blotting assay. Our results showed that regulation of 14-3-3zeta expression influenced the activity of HIF-1alpha, phosphatidyl inositol 3-kinase (PI3K), Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), and nuclear factor kappa B (NF-kB). Blocking of these pathways using indicated inhibitors revealed that 14 3-3zeta enhanced the production of HIF-1alpha via the activation of PI3K/Akt/NF kB pathway, which was identical to hypoxia induced HIF-1alpha expression. For the first time, our study described the key role of 14-3-3zeta in the HIF-1alpha production in HCC cells. And the molecule exerted its function on HIF-1alpha both by directly binding to it and via PI3K/Akt/NF-kB signal transduction pathway. PMID- 26884856 TI - Transplantation of umbilical cord mesenchymal stem cells via different routes in rats with acute liver failure. AB - OBJECTIVE: This study aimed to compare the therapeutic efficacy of transplantation of human umbilical cord mesenchymal stem cells (hUCMSC) in different routes in acute hepatic failure (ALF) in rats. METHODS: hUCMSCs were isolated and identified by detection of surface antigens via flow cytometry. In T group and H group, ALF rats received hUCMSC transplantation through the tail vein and intrahepatic injection, respectively. In hUCMSC group, healthy rats received hUCMSCs transplantation via the tail vein. In ALF group, rats received injection of normal saline through the tail vein. RESULTS: The TBil and ALT in ALF rats with and without transplantation were significantly higher than in healthy rats (P<0.05). HE staining of the liver showed obvious hepatocyte regeneration and reduced infiltration of inflammatory cells, and liver pathology was improved in T group and H group as compared to ALF group. At 3 d after transplantation, CK18 expression was detectable in both H group and T group. At 1 w and 2 w, the mRNA expressions of CK8, CK18 and AFP in H group and T group were significantly different from those in ALF group (P<0.05). The liver function and differentiation of stem cells were comparable between H group and T group (P>0.05). CONCLUSION: hUCMSCs transplantation can improve the liver function and promote the liver repair following ALF. hUCMSCs transplantation via tail vein has similar therapeutic efficacy to that through intrahepatic injection. PMID- 26884857 TI - Effect of halofuginone on the inhibition of proliferation and invasion of hepatocellular carcinoma HepG2 cell line. AB - Primary liver cancer is a common cancer and the mortality of liver cancer ranks the second of all malignancy-related deaths in China. The most common primary liver cancer is hepatocellular carcinoma, accounting for approximately 90% of the total. Because liver is the largest parenchymatous organ in the body undertaking all kinds of important metabolic functions, liver cancer inevitably causes greater harms and its treatment is extremely difficult. Currently, there are still no effective drugs for the treatment of patients with advanced inoperable liver cancer. We observed the strong inhibitory activity of halofuginone on HepG2 cell growth and the cell cycle and apoptosis assays showed that halofuginone arrested the cell cycle and inhibited the induction. And we found that halofuginone inhibits tumor cell cycle possibly by up-regulating p15 and p21 of expression. Then, we found that the proportion of cleaved PARP, caspase-3, 8 and 9 in HepG2 cells increased after halofuginone treatment. And the results showed that halofuginone down-regulated Mcl-1 and c-IAP1 expression. Finally, our results showed halofuginone regulated the activities of JNK and MEK/ERK signaling pathways in hepatocellular carcinoma cells. In summary, this study shows that halofuginone can inhibit the in vitro growth, arrest the cell cycle and induce the apoptosis of HepG2 cells. Its mechanisms of action may be related to the regulation of associated protein expression, up-regulation of JNK, and inhibition of MEK/ERK signaling pathway. PMID- 26884858 TI - Neuroprotective effects and impact on caspase-12 expression of tauroursodeoxycholic acid after acute spinal cord injury in rats. AB - OBJECTIVE: To observe the effects of tauroursodeoxycholic acid (TUDCA) on nerve function after acute spinal cord injury (SCI) in rats, observe its effect on neuronal apoptosis and caspase-12 expression levels, and investigate the underlying mechanism. METHODS: We used a modified Allen's weight-drop trauma method to establish a rat acute SCI model. The rats were randomly divided into three groups: group A (sham surgery group), group B (DMSO control group) and group C (TUDCA treatment group), with 36 rats in each group. At one minute and at 24 hours after successfully establishing the model, rats in group C received an intraperitoneal injection of TUDCA (200 mg/kg), while rats in group B received an equal amount of DMSO at the same time points. At 24 hours, three days, and five days after injury, a modified Tarlov scoring method and Rivlin's oblique plate test were used to evaluate rat spinal cord nerve function recovery. Animals were sacrificed at 24 hours, three days, and five days after injury. Specimens were obtained from the center of the injury sites; the pathological changes in spinal cord tissue were observed after hematoxylin-eosin (HE) staining; apoptosis was detected using the TUNEL method, and the expression of caspase-12 was measured at the protein level using immunohistochemistry and Western blots. RESULTS: Group C differed significantly from group B in Tarlov scores and the oblique table test as early as 24 hours after the injury (P < 0.05). The TUNEL assay test results showed that neurons underwent apoptosis after SCI, which peaked at 24 hours. The ratios of apoptotic cells in group C were significantly lower than those in group B at 24 hours, three days, and five days after injury (P < 0.01). The immunohistochemistry and Western blot results showed that the caspase-12 expression levels of group C were lower than those of group B at 24 hours, three days, and five days after injury (P < 0.05). CONCLUSION: TUDCA can inhibit the expression of caspase-12 in rat neurons after SCI, reduce cell apoptosis, and exert neuroprotective effects on rat secondary nerve injuries after SCI. PMID- 26884859 TI - IVIG inhibits TNF-alpha-induced MMP9 expression and activity in monocytes by suppressing NF-kappaB and P38 MAPK activation. AB - Matrix metalloproteinase-9 (MMP9) has been involved in inflammatory and pathologic processes of coronary artery lesions (CAL) in Kawasaki disease (KD). Intravenous immunoglobulin (IVIG), a traditional treatment for Kawasaki disease, could decrease the expressions of MMP9. The purpose of this study was to investigate the protective effect of IVIG in chemotactic migration of monocyte and the regulation of MMP9 induced by tumor necrosis factor-alpha (TNF-alpha) in U937s. Studies were carried out with real time polymerase chain reaction (RT PCR), zymographic, Western blotting and immunofluorescence. U937s' migration was enhanced by TNF-alpha stimulation, while was inhibited by IVIG pretreatment. MMP9 expression and activity in U937s were also significantly enhanced by TNF-alpha and inhibited by IVIVG pretreatment. During inflammatory stimulus, nuclear factor kappa B (NF-kappaB) and P38 Mitogenactivated protein kinase (P38 MAPK) pathways play a significant role in regulating MMP9 gene expression. TNF-alpha induced nuclear translocation of NF-kappaB and P38 MAPK activation in U937s were inhibited significantly by IVIG. Furthermore, we clarified that nuclear NF-kappaB and P38 MAPK pathways play pivotal roles in regulating U937s' migration and MMP9 expressions using PDTC and SB203580, which were specific inhibitors of NF-kappaB and p38 MAPK pathways. IVIG displays striking biological effects, notably promoting monocyte migration. These effects involve the NF-kappaB and p38 pathways, and increased MMP9 activity. It might be a crucial mechanism of IVIG reducing the occurrence of CAL that IVIG inhibited monocytes expressing MMP9 and decreased chemotactic migration of monocyte. PMID- 26884860 TI - Elevated nuclear CCND1 expression confers an unfavorable prognosis for early stage lung adenocarcinoma patients. AB - PURPOSES: To examine the expression pattern of CCND1 and analyze the correlation of its nuclear expression with clinicopathologic features and prognosis in lung adenocarcinoma. METHODS: CCND1 mRNA and protein levels in lung adenocarcinoma tissues were examined. The relationship between nuclear CCND1 protein expression and clinical features including survival prognosis was analyzed. RESULTS: CCND1 mRNA levels were markedly increased in lung adenocarcinoma (P=0.0019). Western blot analysis confirmed increased nuclear CCND1 protein expression in lung adenocarcinoma specimens. Immunohistochemistry analysis confirmed that CCND1 protein was predominantly nuclear localized in lung adenocarcinoma cells and significantly elevated relative to normal lung tissues (P<0.001). Furthermore, high levels of nuclear CCND1 were positively correlated with clinical stage (P=0.026). Patients with nuclear CCND1 expression had a significantly shorter overall survival time than did patients with low expression. Interestingly, nuclear CCND1 expression in clinical stage I+II, but not clinical stage III, was shown associated with poor prognosis and shorter overall survival time for lung adenocarcinoma patients by strata analysis. Finally, nuclear CCND1 expression tended to be an independent prognostic indicator (P=0.087) for lung adenocarcinoma patient survival. CONCLUSION: Increased nuclear CCND1 is a potential unfavorable prognostic factor for lung adenocarcinoma patients, especially those with clinical early stage (stage I+II). PMID- 26884861 TI - Overexpression of PAK-1 is an independent predictor of disease recurrence in colorectal carcinoma. AB - BACKGROUND: Colorectal carcinoma (CRC) is a significant cause of major morbidity and mortality. PAK-1 is a protein that regulates cytoskeletal dynamics and cell motility. The purpose of the present study is to investigate the relationship between PAK-1 immunoexpression and CRC progression and its validity as an independent prognostic factor. PATIENTS AND METHODS: Paraffin blocks of 103 primary CRCs and 37 nodal metastases were retrieved and tissue microarrays were constructed. Immunohistochemistry was performed using anti-PAK-1 antibody. Immunostaining was scored and results were analysed in relation to clinicopathological parameters. RESULTS: PAK-1 was overexpressed in primary CRC (P<0.001). No difference between low and high expression in nodal metastasis (P=0.139). There was no difference between PAK-1 immunoexpression in primary and nodal metastasis (P=0.275). High PAK-1 immunoexpression was associated with disease recurrence (P=0.03). However, there was no association with most clinicopathological parameters. PAK-1 overexpression was detected as an independent predictor of disease recurrence (P=0.05). No association was found between PAK-1 immunoexpression and disease free survival (log-rank =1.287, P=0.257). CONCLUSION: PAK-1 overexpression may be involved in CRC progression and could be considered an independent predictor of disease recurrence. Further in vivo and in vitro molecular studies are needed to investigate the role of PAK-1 in colorectal carcinogenesis. PMID- 26884863 TI - 17beta-estradiol activates mTOR in chondrocytes by AKT-dependent and AKT independent signaling pathways. AB - To confirm whether 17beta-estradiol (E2) activates mammalian target of rapamycin (mTOR) signaling pathway in chondrocytes and in what way activates mTOR. Human immortalized chondrocytes cell lines TC28a2 and C28/I2 were subjected to incubate with or without E2, LY294002 (the inhibitor of PI3K), rapamycin (the inhibitor of mTOR), or E2 in combination with LY294002 or rapamycin. Thereafter, protein levels of S6K1, p-S6K1, protein kinase B (AKT), and p-AKT were determined by Western blot analysis. Matrix metallopeptidase (MMP) 3 or MMP13 mRNA levels were evaluated by quantitative real-time PCR (qRT-PCR). Co-immunoprecipitation and Western blot analysis were performed to verify the interaction between ERalpha and mTOR. Both p-S6K1 and p-AKT protein levels in TC28a2 and C28/I2E2 cells were significantly increased by incubation with E2 (0.5 h and 1 h) (P < 0.05). Rapamycin did not affect the levels of p-AKT, but were significantly reduced by LY294002 or E2 in combination with LY294002. The levels of p-S6K1 were significantly decreased by incubation with LY294002, but the effect could be reversed by E2 in combination with LY294002. Rabbit anti-mTOR antibody was able to immunoprecipitate ERalpha after incubation with E2. Moreover, E2 inhibited the mRNA levels of MMP3 and MMP13 by mTOR pathway. E2 actives mTOR in chondrocytes through AKT-dependent and independent ways. PMID- 26884862 TI - MALAT1 is an oncogenic long non-coding RNA associated with tumor invasion in non small cell lung cancer regulated by DNA methylation. AB - MALAT1 is an important long noncoding RNA in tumor progression. Here we showed that the expression of MALAT1 was upregulated in non-small cell lung cancer cells (NSCLCs) or tissues as compared with the normal lung cell or tissues. Thus, the knockdown of MALAT1 led to decreased cell migration and invasion. Next we also found that CXCL5 as a downstream gene of MALAT1 regulated cell migration and invasion. However the regulation of MALAT1 expression was rarely known. Here we found that the treatment with SAM suppressed of MALAT1 expression. Finally, we showed that the methylated forms of MALAT1 promoter in lung cancer cells or tissues decreased compared with normal lung cells or tissues. These demonstrated that the expression of MALAT1 was dependent on the methylation. Overall, our findings illuminate the oncogenic function of MALAT1 which is regulated by DNA methylation that might provide potential clinical application in NSCLC. PMID- 26884864 TI - PAI-1 and TNF-alpha profiles of adipose tissue in obese cardiovascular disease patients. AB - Obesity as a leading preventable cause of death worldwide is closely linked to cardiovascular disease (CVD). Plasma plasminogen activator inhibitor (PAI)-1, a potent inhibitor of plasminogen activation and fibrinolysis, is increased in many clinical situations associated with high incidence of CVD. In the obesity-linked elevation of PAI-1, evidence points to TNF-alpha as an important regulator of PAI 1 expression in adipose tissue. BACKGROUND: This study aims to evaluate mediastinal PAI-1 and TNF-alpha mRNA levels in adipose tissues (AT) and compare serum levels in obesity with and without coronary artery disease (CAD). PATIENTS AND METHODS: Obese patients with (n=37) and without CAD (n=20) were included in the study. RESULTS: The serum levels of PAI-1 and TNF-alpha were significantly higher in obese patients with CAD compared to obese patients without CAD. PAI-1 mRNA expression was significantly increased in mediastinal adipose tissue (MAT) of obese patients with CAD compared to those without CAD, TNF-alpha mRNA expressions were found to be higher in EAT (epicardial AT), MAT and SAT (subcutaneous AT) of obese patients with CAD. CONCLUSIONS: The study demonstrated a close direct relationship between TNF-alpha and PAI-1. PAI-1 mRNA expression strongly correlated positively with serum TNF-alpha in MAT, and TNF-alpha expressions with PAI-1 serum levels. PMID- 26884865 TI - Anacardic acid sensitizes prostate cancer cells to radiation therapy by regulating H2AX expression. AB - Anacardic acid (6-pentadecylsalicylic acid, AA), a natural compound isolated from the traditional medicine Amphipterygiumadstringens, has been reported as potential antitumor agents in various cancers including prostate cancer (PC). However, the effects and mechanism of AA on the radiosensitivity of prostate cancer remains unknown. The results indicated that AA exhibited strong antitumor activity in PC cell lines, either as a single agentor in combination with radiation. AA significantly induced the downregulation of H2AX and p-H2AX expression, increase of cell apoptosis and decreasing of cell invasion, which were reversed by overexpressed H2AX. These results suggest that AA sensitize prostate cancer cells to radiation therapy by repressing H2AX expression. PMID- 26884867 TI - HMGB1 silence could promote MCF-7 cell apoptosis and inhibit invasion and metastasis. AB - High mobility group box 1 (HMGB1), a non-histone nuclear protein, was associated with a variety of biological important processes, such as transcription, differentiation, extracellular signaling. As a cytokine or inflammatory mediator, more and more data showed that HMGB1 was involved in inflammatory diseases, cancers or autoimmune disease. However, few data focused on nucleic or cytoplasmic function of HMGB1. Therefore, the present study focused on cancer cells biological characteristics following HMGB1 silence. HMGB1 siRNAs were designed and chemically synthesized, and then transfected into the breast cancer cell line MCF-7 with lipofectamine 2000. The transcription and translation level of HMGB1 expression, proliferation, apoptosis, migration of MCF-7 were determined. The results demonstrated that HMGB1 silence inhibit invasion and migration and promote apoptosis of human breast cells; which indicated that HMGB1 silence might be a potential therapy targets. PMID- 26884868 TI - MAPK1 up-regulates the expression of MALAT1 to promote the proliferation of cardiomyocytes through PI3K/AKT signaling pathway. AB - The previous studies identify mammalian heart is terminal differentiation organs without regenerative capacity. Recently, there is some evidence point that cardiomyocytes are not terminally differentiated cells and cell proliferation may be stimulated in the pathologic heart. The aim of this study is to discover the possible mechanism which involved in cardiomyocytes proliferation process. In this study, the proliferation assay and cell cycle assay showed the proliferation of cardiomyocytes was inhibited when the cells treated with MAPK1 inhibitor. Moreover, the bioinformatics analysis revealed MAPK1 was positively correlated with MALAT1. Meanwhile, the expression of MALAT1 in H9C2 cells with the treatment of MAPK1 siRNA was obvious lower than scramble siRNA treated group. Finally further study suggested H9C2 cells treated with Wortmannin in combination with LY294002 (PI3K/AKT signaling pathway inhibitor), the expression of MALAT1 was dramatically decreased. These results indicated that MAPK1 was able to increase the proliferation of cardiomyocytes via up-regulating the expression of MALAT1 through PI3K/AKT signaling pathway. PMID- 26884866 TI - Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma. AB - The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma. PMID- 26884869 TI - Inhibition of acute lung injury by rubriflordilactone in LPS-induced rat model through suppression of inflammatory factor expression. AB - The present study demonstrates the effect of rubriflordilactone on lipopolysaccharide (LPS)-induced acute kidney injury in rats and MLE-15 cells. LPS administration in rats resulted in formation of edema which was inhibited by pretreatment with rubriflordilactone. The pulmonary tissues of LPS administered rats and MLE-15 cells showed a significant increase in the expression of matrix metalloproteinase-9, interleukin-6 and inducible nitric oxide synthase. However, rubriflordilactone treatment prior to LPS administration caused a significant reduction in the expression of these factors at a concentration of 10 nm/kg. Analysis of the Sirtuin 1 (Sirt1) expression revealed significant (P=0.002) reduction on exposure to LPS in MLE-15 cells. However, rubriflordilactone treatment at 10 nm/ml concentration before LPS exposure caused inhibition of LPS induced reduction in Sirt1 expression. Silencing of Sirt1 by siRNA in MLE-15 cells led to inhibition of increased Sirt1 expression by rubriflordilactone in LPS administered rats. These findings suggest that rubriflordilactone inhibits LPS induced acute lung injury in rats and MLE-15 cells through promotion of Sirt1 expression. PMID- 26884870 TI - Differences in extension patterns between adenoid cystic carcinoma of the nasopharynx and nasopharyngeal carcinoma on MRI. AB - OBJECTIVE: This study aimed to map differences in extension patterns between adenoid cystic carcinoma (ACC) of the nasopharynxandnasopharyngeal carcinomaon magnetic resonance imaging (MRI) and provide more information for treatments. METHODS: MRI examinations and clinical records were reviewed in 18 patients with ACC of the nasopharynx and 182 patients with nasopharyngeal carcinoma (NPC). All patients had biopsy to confirm diagnosis. Differences between NPC and ACC in terms of extension patterns were identified by the retrospective analysis of images from patients undergoing MRI. RESULTS: Patients with ACC of the nasopharynx obtained a higher rate of staging T4 (14.3% vs. 38.9%, P = 0.007) and paralyzed cranial nerves (6.0% vs. 38.9%, P < 0.001). Epstein-Barr (EB) virus infection was not correlated with ACC incidence. No significant difference was observed in invasion to skull base between ACC of the nasopharynx and NPC (53.3% vs. 66.7%, P = 0.277). Involvement of cranial nerve canal (32.4% vs. 55.6%, P = 0.049) and cavernous sinus (13.7% vs. 33.3%, P = 0.028) was more frequently detected by MRI on patients with ACC of the nasopharynx. Lymph node metastasis was infrequently diagnosed in patients with ACC of the nasopharynx. CONCLUSION: As seen on MRI images, ACC of the nasopharynx is characterized by a high incidence of perineural invasion, frequent and aggressive local infiltration, and infrequently, lymph node metastasis. PMID- 26884871 TI - Clinico-pathological characteristics and prognostic factors of gastrointestinal stromal tumors among a Chinese population. AB - Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumors of the digestive tract. GISTs include a group of heterogeneous tumors with different morphology, biologic behavior, and genetic characteristics, so their epidemiology, clinico-pathological features and prognosis is distinct in different countries. The objective of this study is to analyze clinico pathological characteristics and prognostic factors of GISTs among Chinese population. We investigated 112 GIST patients were diagnosed between July 2008 and January 2013 at the First Affiliated Hospital of Guangxi Medical University. Histologic evaluation and immunohistochemistry analysis was performed on paraffin embedded tissue from the 112 GISTs. Overall survival analysis was carried out using the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed according to Cox's proportional hazards model. Three and 5-year OS rates were 71.4 and 58.6% respectively. Univariate analysis showed that the following factors were significant in predicting OS: tumor site, tumor size, metastasis, resection margin status, cell type, invasion of adjacent organ, invasion of smooth muscle, mitotic rate, P53 and adjuvant therapy with imatinib (P<0.05). Multivariate analysis showed that tumor size, metastasis, resection margin status, mitotic rate, P53 and adjuvant therapy with imatinib were independent prognostic factors associated with OS. This may aid in the prediction of clinical evolution and guide treatments in patients with GIST in China. PMID- 26884872 TI - Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal. AB - OBJECTIVE: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. MATERIALS AND METHODS: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, alphaSMA, desmin, caldesmon and mast cell antigen. RESULTS: All leiomyomas showed diffuse positivity for alphaSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CONCLUSION: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors. PMID- 26884873 TI - Effect of bone marrow mesenchymal stem cells transplantation on the serum and liver HMGB1 expression in rats with acute liver failure. AB - OBJECTIVE: This study aimed to investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of high mobility group box 1 protein (HMGB1) in the serum and liver of rats with acute liver failure (ALF). METHODS: Healthy male SD rats were randomly divided into control group, ALF group and BMSCs group. ALF was induced by intraperitoneal injection of 900 mg/kg D-GalN and 10 MUg/kg LPS. In BMSCs group, rats received BMSCs (1.0*10(7)) transplantation via the tail vein at 2 h after ALF induction. RESULTS: Intraperitoneal injection of 900 mg/kg D-GalN and 10 MUg/kg LPS was able to induce ALF in rats. In ALF group, serum ALT and AST increased gradually over time. At 72 h, the serum ALT and AST in BMSCs group were significantly different from those in ALF group. HMGB1 expression in the serum and liver remained at a low level at any time point in control group, but increased significantly in ALF group and BMSCs group. The serum and liver HMGB1 expression increased progressively in ALF group, but reduced gradually in BMSCs group. Significant difference in serum and liver HMGB1 expression was observed between ALF group and BMSCs group at 24 h and 72 h. In addition, there was marked difference in the survival rate among three groups at 24 h (chi (2) =21.098, P<0.01). CONCLUSION: BMSCs transplantation is able to improve the liver function and liver pathology in ALF rats and decrease the serum and liver HMGB1. PMID- 26884874 TI - Effect of immobilization stress on the appetite and stomach ghrelin expression in maternal mice. AB - Maternal stress exerts long-lasting postnatal growth on offspring, which persist into adulthood. However, the effect of maternal stress on appetizing system has not been widely reported. In this study, we found that maternal immobilization stress (IS) during lactation resulted in low body weight and food intake. Immunohistochemistry showed an increase in stomach ghrelin protein expression. The central regulation of body weight and food intake occurs in the hypothalamus, which contains multiple neuronal systems that play important roles in the regulation of energy homeostasis. These systems including multiple neuropeptides involve in the ghrelin pathway of appetite regulation. Therefore, real time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the change of mRNA expression of ghrelin pathway related hormones in order to explore the mechanisms involved in the appetite regulation. Expression levels of the hypothalamic 5-hydroxytryptamine 2c receptor (5-HT2cR) and 5-HT2bR, which are essential for the development and function of ghrelin and leptin, were decreased, as well as those of corticotrophin releasing factor (CRF) and pro opiomelanocortin (POMC). While the expression of growth hormone secretagogue receptor (GHSR), neuropeptide-Y (NPY) and agouti-related protein (AgRP) showed an increase with significant difference. These results suggest that stress in a postpartum mother has persistent effects on the body weight of their offspring. Increased ghrelin and decreased leptin expression in the stomach may play a role in these effects. PMID- 26884875 TI - Serum Interleukin-33 level in Saudi children with inflammatory bowel disease. AB - Interleukin-33 (IL-33) is a cytokine that belongs to the interleukin-1 family and has been shown to be associated with mucosal inflammation. The aim of this study was to determine the serum level of IL-33 in children with ulcerative colitis (UC) and Crohn's disease (CD) and to correlate the level with the disease progression. In this cross sectional prospective study, we enrolled 50 children with IBD from KAUH, Jeddah, Saudi Arabia and 34 healthy control subjects between June 2012 and December 2012. Serum IL-33 was assessed by ELISA and CRP by immunonephelometric assay. Results from our study showed 32 CD and 18 UC patients included. The median age was 13.5 years for CD patients, 11.9 years for UC patients and 11.2 years for controls. Females constituted 53%, 66.7% and 59% of CD, UC and control subjects respectively. The median serum IL-33 in UC patients of 55.5 pg/mL was significantly higher than the median IL-33 level of 41 pg/mL in the healthy control (P=0.04) but no significant difference was found between the median IL-33 level in the sera of CD and the control group (P=0.7). A higher median IL-33 level was also found in active disease (P=0.03). In our cohort, the serum level of IL-33 was positively correlated with hs-CRP (r=0.48, P < 0.001). To conclude, our results support that serum IL-33 level is increased in children with UC as compared with control. Serum level is correlated with the disease activity; therefore it could be used as a potential biomarker for monitoring the severity of the disease in children with UC. PMID- 26884876 TI - Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer. AB - Interferon-induced transmembrane protein 1 (IFITM1) has recently been implicated in tumorigenesis. However, the prognostic value of IFITM1 in colorectal cancer remains unknown. The present study aimed to examine the expression and prognostic significance of IFITM1 in human colorectal cancer. IFITM1 expression was analyzed in 144 archived, paraffin-embedded colorectal cancer tissues and corresponding normal colorectal mucosa by immunohistochemistry. The correlation of IFITM1 with clinic-pathological features and overall survival of colorectal cancer patients was evaluated. IFITM1 was overexpressed in colonic cancer tissues but not in rectal cancer tissues, compared to control normal tissues. The expression of IFITM1 was significantly higher in patients with poor differentiation (P=0.031). The patients with higher IFITM1 expression had worse overall survival outcomes than those with lower IFITM1 expression in rectal cancer (P=0.037). Univariate Cox regression suggested that older age and poorly differentiation status predict shorter overall survival in colorectal cancer (P<0.05). However, IFITM1 expression was not a significant prognostic factor for survival by univariate or multivariate analyses. In conclusion, high expression of IFITM1 is associated with poor prognosis of rectal cancer. IFITM1 may serve as an independent prognostic biomarker for colorectal cancer. PMID- 26884877 TI - Circulating miR-122-5p as a potential novel biomarker for diagnosis of acute myocardial infarction. AB - BACKGROUND: MicroRNAs (miRNAs) play key roles in cardiac development, and the expression of miRNAs is altered in the diseased heart. The aim of this study was to explore the value of circulating microRNA-122-5p (miR-122-5p) as a potential biomarker for acute myocardial infarction (AMI). METHODS: Plasma samples from 50 patients with AMI and 39 healthy adults (non-AMI controls) were collected. The abundance of circulating miR-122-5p was measured using quantitative real-time PCR (qRT-PCR). The cTnI concentrations of these samples were analyzed by ELISA. RESULTS: Our findings revealed that circulating miR-122-5p expression were increased in AMI patients at 4 h, 8 h, 12 h, and 24 h by contrast to those non AMI controls and displayed similar trends to that of cTnI concentrations in AMI patients. Further study showed that there is a high correlation between circulating miR-122-5p and cTnI concentrations. At last, the receiver operating characteristic (ROC) curve was performed and showed that circulating miR-122-5p had considerable diagnostic accuracy for AMI with an area under curve (AUC) of 0.855. CONCLUSIONS: Our results implied that circulating miR-122-5p could be a potential biomarker for AMI. PMID- 26884878 TI - Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances. AB - Circular RNA (circRNA) is a type of RNAs which, unlike the better known linear RNA, forms a covalently closed continuous loop. They have emerged recently as a new player in governing fundamental biological processes. However it remains elusive about the correlation of hsa_circ_001988 abundance with colorectal cancer. To investigate the circular RNA expression in colorectal cancer, the targeted hsa_circ_001988 was selected from next generation sequence data base generated in house and then designed divergent primers to amplify hsa_circ_001988 and sequenced it for validation. The expression of hsa_circ_001988 in 31 matched colorectal cancer tissue and normal colon mucosa was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). We used DeltaCt method and investigated the differences between tumor tissues and normal colon mucosa by paired t-test. One-way analysis of variance was conducted to analyze the relationship between hsa_circ_001988 expression level and clinic pathological factors of patients. Receiver operating characteristic (ROC) curve was built by SPSS to evaluate the diagnostic values. The expression of hsa_circ_001988 was significantly correlated with differentiation (P<0.05) and perineural invasion (P<0.05). The area under ROC curve of hsa_circ_001988 was 0.788 (P<0.05). Those results indicate that hsa_circ_001988 may become a novel potential biomarker in the diagnosis of colorectal cancer and a potential novel target for the treatment of colorectal cancer. PMID- 26884879 TI - Expression of PI3Kp110alpha and PI3Kp110beta in the colorectal conventional adenoma, serrated lesions and adenoma with canceration and their significance. AB - AIMS: To evaluate the expression and clinical significance of PI3Kp110alpha and PI3Kp110beta in colorectal conventional adenoma, serrated lesions and adenoma with canceration. METHODS AND RESULTS: Immunohistochemistry and Western blot analysis were conducted to detect the expression of p110alpha and p110beta in normal colorectal tissues, conventional adenoma, serrated lesions and adenoma canceration. Results revealed that the expression of P110alpha and P110beta in the adenoma canceration was significantly higher than that in normal tissues, tubular adenoma (low grade) and tubular-villous adenoma (low grade) of conventional adenoma, hyperplastic polyps of serrated lesions (P<0.05). But there was no significant difference between the adenoma canceration and the high grade adenoma of conventional adenoma, all grade of villous adenoma and serrated adenoma (P>0.05). The expression of p110alpha and p110beta was correlated with different clinicopathologic factors in conventional adenoma, serrated adenoma and adenoma canceration (P<0.05). CONCLUSIONS: p110alpha and p110beta were highly expressed in villous adenoma, serrated adenoma and adenoma with canceration. Its high expression may be the risk factor of the progress of adenoma to adenocarcinoma, and may be an important cause of what canceration rate of villous adenoma and serrated adenoma was higher than that of other adenomas. Combined detection of p110alpha and p110beta is helpful to determine the canceration potential of colorectal villous adenoma and serrated adenoma. PMID- 26884880 TI - Senile cataract and genetic polymorphisms of APE1, XRCC1 and OGG1. AB - Polymorphisms of DNA repair enzymes which may influence their repair efficiency lead to diseases, for example, senile cataract. In this study, we aimed to analyze the association of single nucleotide polymorphisms in AP endonuclease-1 (APE1), 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross-complementing-1 (XRCC1) genes with the risk of age-related cataract in a Chinese population. Genotyping was carried out by the polymerase chain reaction and DNA sequencing on 402 cataract patients and 813 controls in this study. Differences in the frequencies were estimated by the chi-square test, and risk was estimated using unconditional logistic regression after adjusting for age and gender. Our results demonstrated there was a significant difference between the case and control groups in the APE1-141 G/G genotype (P=0.002). This difference still existed after adjusting for age and gender (P*=0.003). The APE1-141 T/T genotype and T allele frequencies were significantly higher in cataract patients, while the G/G genotype and G allele frequencies in patients were significantly lower than in controls (P < 0.05). The APE1-141 G/G genotype (OR, 0.49; 95% CI, 0.31-0.77) seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. In OGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls. PMID- 26884882 TI - Genetic polymorphisms of C-reactive protein increase susceptibility to HBV related hepatocellular carcinoma in a Guangxi male population. AB - C-reactive protein (CRP) is a biomarker of inflammation and the production has been shown to be influenced by genetic variation in CRP gene. HBV-related hepatocellular carcinoma (HCC) is a typical inflammation-related disease occurs mainly in men. The present study was designed to investigate the association between CRP polymorphisms and HBV-related HCC risk in a Chinese male population. The CRP rs2794521 and rs3093059 SNPs were genotyped by polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP) in 158 HBV patients with HCC, 207 HBV patients without HCC, and 150 unrelated healthy controls. A significant increased HCC risk in HBV patients were observed for the rs3093059 SNP comparing with those without HCC (C allele vs. T allele: adjusted OR=1.56, 95% CI, 1.07-2.29, P=0.021; TC vs. TT: adjusted OR=1.77, 95% CI, 1.13-2.76, P=0.012; TC/CC vs. TT: adjusted OR=1.76, 95% CI, 1.14-2.71, P=0.011). However, we did not observe any significant association of rs3093059 polymorphism with HCC when compared with healthy controls. With respect to rs2794521 polymorphism, no significant associations of this polymorphism with HCC risk were found in this population. In haplotype analysis between HBV patients with HCC and HBV patients without HCC, the TC haplotype was found correlated with a significant increased HCC risk (OR=1.803, 95% CI, 1.237-2.335, P<0.001). We concluded that the CRP rs3093059 polymorphism may play a significant role in the development of HBV related HCC in the Guangxi male population. PMID- 26884881 TI - Latent transforming growth factor-beta binding protein-1 in circulating plasma as a novel biomarker for early detection of hepatocellular carcinoma. AB - This study aimed to assess the diagnostic value of the latent transforming growth factor-beta binding protein-1 (LTBP-1) in distinguishing hepatocellular carcinoma (HCC) from patients with hepatitis or liver cirrhosis. The protein levels of LTBP 1 or AFP in circulating plasma were measured by enzyme-linked immunosorbent assay (ELISA) or chemiluminescence in four cohorts: HCC (n = 167), liver cirrhosis (n = 50), chronic hepatitis B (CHB, n = 50), and healthy individuals (n = 104). Receiver operating characteristics (ROC) curves and area under the curves (AUC) of the proteins were calculated. Results showed that plasma levels of LTBP-1 were significantly higher in HCC patients than those in other three groups. LTBP-1 showed a better diagnostic performance (AUC = 0.74, 95% CI: 0.67-0.80) in distinguishing HCC from the CHB or cirrhosis patients, compared to AFP (AUC = 0.59, 95% CI: 0.52-0.65). In the early-stage HCCs investigated, diagnostic performance of LTBP-1 (AUC = 0.77, 95% CI: 0.70-0.84) remained better than that of AFP (AUC = 0.61, 95% CI: 0.52-0.69). Combination of LTBP-1 and AFP showed increased diagnostic efficiency than any of the two proteins performed alone, for both all HCC (AUC = 0.78, 95% CI: 0.72-0.83) and early-stage HCC (AUC = 0.80, 95% CI: 0.74-0.87). These findings proposed that LTBP-1 may be a promising biomarker for distinguishing HCC from the CHB or liver cirrhosis patients, especially for the early-stage HCC. PMID- 26884883 TI - (99m)Tc-3P-RGD2 SPECT to monitor early response to bevacizumab therapy in patients with advanced non-small cell lung cancer. AB - The present study assessed the predictive value of (99m)Tc-3(poly-(ethylene glycol), PEG) 4-arginine-glycine-aspartic ((99m)Tc-3P-RGD2) single photon emission computed tomography (SPECT) for the early identification of response to antiangiogenic treatment with bevacizumab in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC treated with bevacizumab were prospectively studied with (99m)Tc-3P-RGD2 SPECT before and after 2 weeks from start of treatment. The tumor response was evaluated with RECIST criteria and related to observed change in the tumor to non-tumor (T/N) ratio for the largest known lesion. Receiver operating characteristic (ROC) curve analysis was used to determine T/N ratio changes with regard to predicting response to bevacizumab therapy. Change in T/N ratio was also related to progression-free survival (PFS) and overall survival (OS). Twenty-six patients were included, and 23 were finally assessable for metabolic response evaluation with (99m)Tc-3P-RGD2 SPECT. The cut-off value of T/N ratio change defined by ROC analysis was 24.4%. The sensitivity, specificity, and negative predictive value of (99m)Tc-3P-RGD2 SPECT for predicting tumor response were 81.8%, 91.7%, and 84.6%, respectively. Using the cut-off value defined by ROC analysis on (99m)Tc-3P-RGD2 SPECT, metabolic non-progressive disease patients (mNP) showed prolonged PFS (5.6 months versus 3.4 months; P < 0.001) and OS (17.1 months versus 8.6 months; P < 0.001) than metabolic progressive disease patients (mP). (99m)Tc-3P-RGD2 SPECT scan is a promising test to predict tumor response in patients with advanced non-small cell lung cancer early in the course of bevacizumab therapy. PMID- 26884884 TI - High expression of dual-specificity phosphatase 5 pseudogene 1 (DUSP5P1) is associated with poor prognosis in acute myeloid leukemia. AB - The purpose of this study was to investigate the expression status of Dual Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time quantitative PCR (RQ-PCR) was performed to detect the status of DUSP5P1 expression in 89 patients with de novo AML and 24 normal controls. The level of DUSP5P1 expression was significantly up-regulated in AML compared to controls (P=0.031). The patients with high expression of DUSP5P1 had higher percentage of blasts in bone marrow (BM) than those without high expression (P=0.027). The occurrence rate of DUSP5P1 high expression was significantly higher in M1 (2/8, 25%) and M2 subtypes (9/33, 27%) than in M3 subtype (0/17, 0%) (P=0.034). At the same time, the frequency of DUSP5P1 high expression in patients with intermediate (13/53, 24%) and poor karyotypes (5/11, 45%) was significantly higher than that in patients with favorable karyotype (0/21, 0%) (P=0.003). Meanwhile, DUSP5P1 high-expressed patients had significantly shorter overall survival (OS) than those with low expression (median 4.5 vs. 10.5 months, respectively, P=0.038). Our findings indicated that high expression of DUSP5P1 may identify high-risk AML patients and is associated with poor prognosis in AML. PMID- 26884885 TI - A three gene-based risk score predicts prognosis of resected non-small-cell lung cancer. AB - BACKGROUND: To study the prognosis-predicting value of a risk score based on phosphorylated At (p-Akt), vascular endothelial growth factor (VEGF), and Nin one binding (NOB1) expression in patients with resected non-small-cell lung cancer (NSCLC). METHODS: A prospective cohort among 98 consecutive patients with resected NSCLC was conducted in 2009 to 2010. Immunohistochemistry was used in the detection of p-Akt, VEGF, and NOB1 expression. Any of three genes with positive expression was allocated a score of 1, otherwise scored 0. The risk score ranged from 0-3. Prognosis outcomes included overall survival (OS) and progression-free survival (PFS). Log-rank test and Cox hazard model were used to investigate the prognosis predicting value for the risk score. RESULTS: In the 98 NSCLC tissue specimens, p-Akt, VEGF and NOB1 positive Expression rates were 42.9%, 66.3%, and 60.2%, respectively. The median for OS was 44 month, with 95% CI 35-51 months, and the median for PFS was 36 months, with 95% CI 25-49 months. Log-rank test showed OS and PFS related with TMN stage, lymph node metastasis, p Akt expression, VEGF expression, NOB1 expression, and gene-based risk score (P<0.05). Multivariate COX analysis showed pTMN stage, lymph node metastasis, p Akt expression, VEGF expression, and gene-based risk score were independent prognosis factors for OS and PFS. The adjusted HR for gene-based risk score with every one score increase was 1.21 [1.04-1.56] for OS and 1.19 [1.02-1.79] for PFS. CONCLUSIONS: Our results suggest the risk scores based on p-Akt, VEGF, NOB1 expression can predict postoperative survival in patients with resected NSCLC. PMID- 26884886 TI - Evaluation of the management of Hr-HPV+/PapTest- women: results at 1-year recall. AB - With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.10/00, and it was 0.20/00 at the 1 year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved. PMID- 26884887 TI - RASSF7 expression and its regulatory roles on apoptosis in human intervertebral disc degeneration. AB - Apoptosis plays an important role in intervertebral disc degeneration (IDD). Overwhelming evidence indicates that RASSF7 is essential for cell growth and apoptosis. Recently, it has been noted that the JNK signaling can be negatively regulated by suppressing phosphorylated-MKK7 activation during pro-apoptosis. We aimed to investigate the RASSF7 expression level in human degenerative nucleus pulposus (NP) cells and non-degenerative NP cells and the link between RASSF7-JNK with NP cells apoptosis. We harvested NP tissues from 20 IDD patients as disease group and 8 cadaveric donors as normal controls. We detected RASSF7 expression by Real-time-PCR and western blotting. Consequently, we found that the expression of RASSF7 was higher in non-degenerative group than in degenerative group (P<0.05). Overexpression of RASSF7 in degenerative NP cells led to decreased apoptosis rate than that in scramble group (P<0.05). Collectively, our findings suggest that RASSF7 plays an important role in human IDD and RASSF7 might be potentially developed as a curative agent. PMID- 26884888 TI - Expression of EBV antibody EA-IgA, Rta-IgG and VCA-IgA and SA in serum and the implication of combined assay in nasopharyngeal carcinoma diagnosis. AB - Epstein-Barr virus (EBV) is an important non-invasive index for nasopharyngeal carcinoma. Serum sialic acid (SA) level was known to be related with tumor progression. Rta protein antibody IgG (Rta-IgG), early antigen antibody (EA-IgA) and viral capsid antibody (VCA-IgA) levels in serum can also be used to effectively monitor the progression of cancer. This study investigated serum level of SA, Rta-IgG, EA-IgA and VCA-IgA in nasopharyngeal cancer patients and the diagnostic value of combined assay. A total of 64 nasopharyngeal cancer patients were recruited, in parallel with 60 benign rhinitis and 60 healthy individuals. Serum SA, EA-IgA, Rta-IgG and VCA-IgA levels were measured by enzyme linked immunosorbent assay (ELISA). The diagnostic value of these indexes was further evaluated by ROC curve analysis. Logistic regression model was used to analyze the diagnostic implication of combined assay. The expression levels of SA, EA-IgA, Rta-IgG, and VCA-IgA were highest in nasopharyngeal cancer patients. Those indexes were also increased with advanced TNM stage of cancer. The overall diagnostic efficacy was ranked as: VCA-IgA, Rta-IgA, EA-IgA and SA. The combined diagnosis increased the sensitivity to 98.44% and the negative predictive value to 99.03%, without compromising specificity. SA, EA-IgA, Rta-IgG and VCA-IgA expression levels were elevated in nasopharyngeal patients. The combined diagnosis of those serum indexes may improve the diagnostic efficacy of nasopharyngeal carcinoma. PMID- 26884889 TI - CT features and pathologic characteristics of IgG4-related systemic disease of submandibular gland. AB - The submandibular gland is one of the most frequently affected salivary gland in IgG4-related systemic disease, usually demonstrate homogeneous attenuation on CT imaging as reported, but without much pathological comparison of many cases. This article is to investigate and analyze the typical CT findings and pathologic characteristics of IgG4-related systemic disease (IgG4-RSD) of submandibular gland. A retrospective analysis of the preoperative CT findings in patients with IgG4-RSD of submandibular glands who underwent surgical resection between January 2010 and February 2014 was performed. Twenty patients (16 women) were identified, with a mean age of 58.1+/-10.2 years. All patients presented with painless submandibular gland swelling. Diffuse gland enlargement, with clear margins and homogeneous density, was found on non-enhanced CT scans in all cases. There were no calcifications or stones within the involved glands. Based on contrast enhanced CT appearance the patients could be divided into two groups: 11 cases showed homogeneous gland enhancement; and multiple hyperenhancing foci, with a crazy-paving pattern, were detected in 9 cases, which were in consistent with the pathologic findings. The maximum submandibular gland diameter on transverse images was significantly larger (P=0.008) in patients with crazy-paving appearance (32+/-4 mm) compared to patients with homogeneous enhancement (28+/-3 mm). It is concluded that the submandibular glands with IgG4-RSD can be characterized by either homogenous appearance or crazy-paving pattern on contrast enhanced CT imaging. PMID- 26884890 TI - Systematic review and meta-analysis of patient-controlled sedation versus intravenous sedation for colonoscopy. AB - BACKGROUND: Patient-controlled sedation (PCS) has been suggested as an alternative method for sedative colonoscopy. However, as any new techniques, PCS introduction as a potential alternative to traditional intravenous sedation (IVS) has brought about challenges. To evaluate the advantages and disadvantages between PCS and IVS more comprehensively, we conducted a systematic review and meta-analysis of the published literature. METHODS: Several databases were searched from inception to 1 April, 2015, for trials comparing PCS with IVS for colonoscopy. The outcomes of interest included time for cecal intubation, rate of complete colonoscopy, dose of sedative drugs used, pain scores, recovery time, complications. Inconsistency was quantified using I (2) statistics. RESULTS: In all, 12 trials were finally selected (1091 patients, with 545 in the PCS group, and 546 in the IVS group). The total propofol used, time for cecal intubation, rate of complete colonoscopy and pain score had no statistical difference between the two groups. However, PCS showed a reduction in the recovery time, incidence of oxygen desaturation and hypotension. The rates of other complications and patients' willingness to repeat the same sedation had no statistical difference between the two groups. CONCLUSION: PCS is as feasible and effective as traditional IVS for colonoscopy, and there is a tendency that PCS shows its superiority in recovery time, incidence for oxygen saturation and hypotension. PMID- 26884891 TI - The origin and onset of acute venous thrombus. AB - Under the condition of immune cell balancing function collapse, acute venous thrombosis originates from intravenous immune adhesive inflammations triggered by cells which are infected by foreign pathogenic microorganism and malignant cells. With the condition of immune cell balancing function collapse, the human body lost the function of clearing intravenous foreign pathogenic microorganism and malignant cells timely and effectively. Thus, integrins beta2 and beta3 on the membrane of white blood cells and platelets are activated to combine with the ligand fibrinogen into a reversible mesh-like structure, which is like the intravenous biological filter and acts as physical defense of the human body to prevent the cells which are infected by foreign pathogenic microorganism and malignant cells in the distal veins from flowing back to the whole body. Meanwhile, blood cells mainly red blood cells stagnate and fulfill the filter, which blocks the blood flow in the local veins and thus results in venous thrombotic diseases. People with collapsed immune cell balancing functions are the certain groups of people who will develop venous thromboembolism. Anyone who had venous thromboembolism indicates alloantigen cells in the veins, which are mainly pathogenic microorganism infected cells and malignant cells and trigger the onset of venous thromboembolism. Only under the condition of immune cell balancing function collapse, the risk factors, such as advanced age, infection, trauma, surgery, autoimmune disease, pregnancy as well as long trip syndrome, could cause venous thromboembolism. PMID- 26884893 TI - Effectiveness of different surgical modalities in the management of temporomandibular joint ankylosis: a meta-analysis. AB - BACKGROUND: A meta-analysis was conducted to evaluate the effectiveness of three surgical modalities-gap arthroplasty (GA), interpositional gap arthroplasty (IPG) and joint reconstruction (AR)-in treating temporomandibular joint (TMJ) ankylosis. METHODS: A systematic review was performed using the PUBMED, EMBASE and OVID search engines in February 2015 to identify cohort studies with no restrictions, with the aim of evaluating the three surgical modalities. The outcome was the change between the pre- and postoperative maximal incisal opening (MIO). Analyses of category, heterogeneity, sensitivity and publication bias were performed. A fixed-effects model was used to compute the pooled weighted mean difference in the MIO among the different groups. RESULT: Seventeen studies with 740 participants were included in the final analysis. The IPG therapy showed a significantly greater MIO when compared to GA (WMD=1.16 mm; 95% CI, 0.15-2.16) and AR (WMD=0.99 mm; 95% CI, 0.05-1.92) therapies. The weighted mean difference between the AR and GA modalities was 2.94 mm (95% CI, 0.12-5.75). The pooled odds ratios (ORs) of the recurrence rate for IPG, GA and AR were 0.01 (95% CI, 0.00 0.03), 0.03 (95% CI, 0.00-0.07) and 0.06 (95% CI, 0.04-0.09), respectively. CONCLUSION: The analysis showed that IPG was more effective and displayed a lower recurrence rate, followed by AR and GA, in treating TMJ ankylosis. Thus, this analysis provides strong evidence supporting IPG as a first-line therapy for TMJ ankylosis. PMID- 26884892 TI - The influence of inpatient comprehensive geriatric care on elderly patients with hip fractures: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: To evaluate the efficacy of in-patient comprehensive geriatric care for elderly patients with hip fracture. METHODS: Relevant literatures were searched using the following databases including PubMed, OVID, Web of science, Scopus, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trails until August 1, 2015. Eligible studies were restricted to randomized controlled trials (RCTs). The available data was extracted by two independent authors and pooled through using Review manager version 5.2. For data deemed not appropriate for synthesis, a narrative overview was conducted. RESULTS: 15 trials evaluating 3458 participants were identified in our meta-analysis. Our findings indicated patients who underwent comprehensive geriatric cares showed no significant greater improvement than control in in-patient mortality (Odds risk (OR) 0.73, 95% confidence interval (CI) 0.51 to 1.05, P=0.09), 3-(OR 0.96, 95% CI 0.51 to 1.81, P=0.90), 6-(OR 1.03, 95% CI 0.73 to 1.45, P=0.86) and 12-months mortality (OR 0.93, 95% CI 0.77 to 1.12, P=0.30). The proportion of patients who were discharged from hospital to the same place of residence as before the fracture was higher in intervention group than control (OR 1.67, 95% CI 0.80 to 3.37, P=0.0003). In addition, the pooled results showed that the number of patients in intervention group who had regained the same level of activities of daily living (ADL) (43.9% vs 30.2%, 46.0% vs 29.1%) and walking ability (71.3% vs 53.2%, 68.9% vs 56.3%) as before the fracture was higher than control at 3 and 12 months after discharge, respectively. CONCLUSION: Comprehensive geriatric care promoted the functional improvement for elderly patients with hip fracture. Meanwhile, the proportion of patients who were discharged from hospital to the same place as before fracture in intervention group was higher as compared to control. However, our finding showed no significant difference on in-patients mortality, follow-up mortality and length of stay between both groups. PMID- 26884894 TI - Leptin and its receptor in hematologic malignancies. AB - Leptin is an adipocyte-derived cytokine coded by the obese gene, not only regulates metabolism, but also participates in hematopoiesis. Aberrant leptin levels in patients with hematologic malignancies were observed and associates with clinical characters, such as body mass index (BMI), gender, blast cell percentage. Leptin concentrations alter while diseases progress or remission. Leptin receptor is expressed in hematopoietic CD34+ stem cells, erythrocytes, lymphocytes, blast cells and samples in leukemia and lymphoma patients. The adipokine stimulates cell proliferation, cytokine secretion and protects malignant cells from apoptosis through Janus kinase-signal transducer and activator of transcription (JAK-STAT), mitogen-activated protein kinase and extracellular signal activated kinase 1/2 (MAPK/ERK1/2), or 3 kinase (PI3K) signaling pathways. These findings indicate leptin signaling possibility take part in occurrence, progression and prognosis of hematologic malignancies. This article reviews leptin/leptin receptor expression and the correlations with clinical characters, treatment and prognosis in myeloid and lymphoid neoplasms. PMID- 26884895 TI - Clinical modalities for management of gastric cancer hepatic metastasis. AB - The best treatment for gastric cancer hepatic metastasis is still widely debated. Gastric cancer hepatic metastases has long been justified the indication of palliative chemotherapy. Inspired by the good results of the management of colorectal cancer hepatic metastases, surgeons have focused on the curative or palliative treatment of gastric cancer hepatic metastases. The current clinical modalities used for treatment of gastric cancer hepatic metastasis include liver resection, systemic chemotherapy, radiofrequency ablation (RFA), hepatic arterial infusion (HAI), and palliative gastrectomy. This article presents a review of the literature on hepatic resection, RFA, HAI, palliative gastrectomy, and systemic chemotherapy for the treatment of liver metastases in gastric carcinoma, and discusses the indications and long-term results. PMID- 26884897 TI - Cytoprotective role of heme oxygenase-1 in liver ischemia reperfusion injury. AB - Ischemia/reperfusion (I/R) injury is the main cause of graft dysfunction and failure in vascular occlusion both during liver surgery and during liver transplantation. The pathophysiology of hepatic ischemia-reperfusion includes a number of mechanisms including oxidant stress that contribute to various degrees to the overall organ damage. Heme oxygenases (HO) are essential enzymes which degrade heme into biliverdin-IXalpha, free divalent iron, and carbon monoxide (CO). Due to its anti-inflammatory, anti-apoptotic and, as recently described, anti-viral properties. The inducible HO isoform HO-1 is an important molecule which could find its way into therapy of acute and chronic liver injuries including acute liver failure, alcoholic or viral hepatitis, chronic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma are life threatening diseases and as a consequence might result in the necessity of liver transplantation. Liver transplantation is limited by ischemia/reperfusion (I/R) injury, which is characterized by hypoxia and nutrient deficiency resulting in oxidative stress, apoptosis and immune activation. Induction of HO-1 and application predominantly of CO have been shown to interfere with liver I/R injury and to improve recipient and graft survival. HO-1 and its reaction products of heme degradation has been linked to cytoprotection, and as an inducible form of HO, serves a vital metabolic function as the rate-limiting step in the heme degradation pathway, and affords protection in models of liver I/R injury. HO-1 system is an important player in liver I/R injury condition, and may offer new targets for the management of this condition. This review aims to summarize cytoprotective role of heme oxygenase-1 (HO-1) and its products within the liver. PMID- 26884896 TI - Physical exercise-induced protection on ischemic cardiovascular and cerebrovascular diseases. AB - Physical exercise is any bodily activity to enhance or maintain physical fitness and overall health and wellness. A series of associated studies have demonstrated that physical exercise could alleviate the infarct volume, increase the collateral circulation, promote endothelial progenitor cells, improve cerebral blood flow after cardiovascular and cerebrovascular diseases. In this review, we summed up the protective effects of physical exercise on cerebral blood flow (CBF), vascular endothelium, vascular vasodilation, endothelial progenitor cells and collateral circulation. An awareness of the exercise intervention benefits for cardiovascular and cerebrovascular diseases may encourage more patients with cerebral infarction and myocardial infarction and people with high risk factors to accept exercise interventions for the prevention and treatment of cardiovascular and cerebrovascular diseases. PMID- 26884898 TI - Tibetan medicine "RNSP" in treatment of Alzheimer disease. AB - Alzheimer disease (Alzheimer Disease, AD) is one of the most common type in senile dementia. Its main pathological features were that a large number of senile plaques gathered in brain extracellular and tangles fibrosis appeared in nerve cells. Currently, the pathogenesis of AD is still uncertain, and scale investigation and combined brain CT, MRI data were analyzed mainly for clinical diagnosis. Mitigation and improvement of the nervous system activity to interfere with the subsequent behavior of the patients are the main methods for treatment. In clinical no drug can really prevent and cure AD. From the view point of Tibetan medicine studies, Tibetan medicine RNSP has effect on improving memory and repairing the neurons in the brain. In this study, we combined the characteristics of AD pathology, pathogenesis, diagnosis and treatment methods to explore the feasibility of Tibetan medicine RNSP for the treatment of AD to provide new ideas for the diagnosis and treatment of AD. PMID- 26884899 TI - Development of prognostic models for patients with traumatic brain injury: a systematic review. AB - Outcome prediction following traumatic brain injury (TBI) is a widely investigated field of research. Several outcome prediction models have been developed for prognosis after TBI. There are two main prognostic models: International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) prognosis calculator and the Corticosteroid Randomization after Significant Head Injury (CRASH) prognosis calculator. The prognosis model has three or four levels: (1) model A included age, motor GCS, and pupil reactivity; (2) model B included predictors from model A with CT characteristics; and (3) model C included predictors from model B with laboratory parameters. In consideration of the fact that interventions after admission, such as ICP management also have prognostic value for outcome predictions and may improve the models' performance, Yuan F et al developed another prediction model (model D) which includes ICP. With the development of molecular biology, a handful of brain injury biomarkers were reported that may improve the predictive power of prognostic models, including neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), S-100beta protein, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), myelin basic protein (MBP), cleaved tau protein (C-tau), spectrin breakdown products (SBDPs), and ubiquitin C-terminal hydrolase-L1 (UCH L1), and sex hormones. A total of 40 manuscripts reporting 11 biomarkers were identified in the literature. Many substances have been implicated as potential biomarkers for TBI; however, no single biomarker has shown the necessary sensitivity and specificity for predicting outcome. The limited number of publications in this field underscores the need for further investigation. Through fluid biomarker analysis, the advent of multi-analyte profiling technology has enabled substantial advances in the diagnosis and treatment of a variety of conditions. Application of this technology to create a bio-signature for TBI using multiple biomarkers in combination will hopefully facilitate much needed advances. We believe that further investigations about brain injury biomarkers may improve the predictive power of the contemporary outcome calculators and prognostic models, and eventually improve the care of patients with TBI. PMID- 26884901 TI - Sorafenib in combination with low-dose-homoharringtonine as a salvage therapy in primary refractory FLT3-ITD-positive AML: a case report and review of literature. AB - The presence of internal tandem duplications (ITD) in the Fms-related tyrosine kinase 3 receptor (FLT3) has been associated with a poor prognosis in acute myeloid leukemia (AML). Over the past decade, FLT3 is a promising target in FLT3 ITD-positive AML. Sorafenib which is one of the commonly focused FLT3 inhibitors may improve outcome, but only few patients display long-term responses in previously reported cases, prompting the search for underlying resistance mechanisms and therapeutic strategies to overcome them. To the best of our knowledge, this is the first case report about sorafenib in combination with low dose-homoharringtonine as a salvage therapy successfully administrated and got complete remission (CR) in primary refractory FLT3-ITD-positive AML. Our result demonstrates the combination of this two drugs may be a good choice for the primary refractory FLT3-ITD-positive AML patient, although cooperative studies of large numbers of these patients are needed to evaluate and optimize this combination. PMID- 26884900 TI - Propranolol treatment of subglottic hemangiomas: a review of the literature. AB - Subglottic hemangiomas (SGH), which are rare benign tumors of the airway, are potentially life-threatening conditions that may require intervention. Propranolol appears to be an effective treatment for these tumors and should therefore be a first-line treatment for SGH that require intervention. This review presents the clinical presentation and diagnosis of SGH and discusses current knowledge regarding the use of propranolol for the treatment of SGH. PMID- 26884902 TI - Temporal and spatial expression of caudal-type homeobox proteins in the midgut of human embryos. AB - BACKGROUND: This study aimed to determine the spatiotemporal expression of caudal type homeobox genes (CDX1, CDX2 and CDX4) during development of the midgut in human embryos and to explore the possible roles of CDX genes during the morphogenesis of human midgut. Human embryos (n=28) were sectioned serially and sagittally and CDX1, CDX2 and CDX4 proteins were detected on the midline from the 5th to 9th weeks of gestation by immunohistochemical staining. RESULTS: CDX1, CDX2 and CDX4 proteins were weakly expressed in epithelium and mesenchyme of the midgut in the 6th and 7th weeks of gestation and reached estimated optimal level on the 8th and 9th weeks of gestation. In the 9th week of gestation, immunoreactivities specific to CDX1, CDX2 and CDX4 were restricted in epithelium of the midgut. CONCLUSIONS: CDX1, CDX2 and CDX4 proteins began to express in human midgut in the 6th week of gestation. From the 6th to 9th week of gastation, the expression of CDX1, CDX2 and CDX4 proteins gradually increase and exhibited overlapping expression patterns, suggesting that CDX genes may be involved in early development of the epithelium of human midgut. Cross-regulatory interactions may exist among CDX genes with respect to human midgut development. PMID- 26884903 TI - Determination of mandibular border and functional movement protocols using an electromagnetic articulograph (EMA). AB - The electromagnetic articulograph (EMA) is a device that can collect movement data by positioning sensors at multiple points, measuring displacements of the structure in real time, as well as the acoustics and mechanics of speech using a microphone connected to the measurement system. The aim of this study is to describe protocols for the generation, measurement and visualization of mandibular border and functional movements in the three spatial planes (frontal, sagittal and horizontal) using the EMA. The EMA has transmitter coils that determine magnetic fields to collect information about movements from sensors located on different structures (tongue, palate, mouth, incisors, skin, etc.) and in every direction in an area of 300 mm. After measurement with the EMA, the information is transferred to a computer and read with the Visartico software to visualize the recording of the mandibular movements registered by the EMA. The sensors placed in the space between the three axes XYZ are observed, and then the plots created from the mandibular movements included in the corresponding protocol can be visualized, enabling interpretation of these data. Four protocols for the obtaining of images of the opening and closing mandibular movements were defined and developed, as well as border movements in the frontal, sagittal and horizontal planes, managing to accurately reproduce Posselt's diagram and Gothic arch on the latter two axes. Measurements with the EMA will allow more exact data to be collected in relation to the mandibular clinical physiology and morphology, which will permit more accurate diagnoses and application of more precise and adjusted treatments in the future. PMID- 26884904 TI - The risk of bradykinin B2 receptor-58T/C gene polymorphism on hypertension: a meta-analysis. AB - BACKGROUND: The risk of bradykinin B2 receptor (BDKRB2) -58T/C gene polymorphism on hypertension remains controversial. MATERIALS AND METHODS: The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. RESULTS: The significant association between BDKRB2-58T/C gene polymorphism and risk of hypertension were found under C-allele comparison [odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05-1.42, recessive model (OR: 1.32, 95% CI: 1.07-1.64), dominant model (OR: 0.74, 95% CI: 0.58-0.94), homozygote model (OR: 1.66, 95% CI: 1.11-2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06-1.43). The magnitude of the association between the BDKRB2-58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C-allele comparison (OR: 1.24, 95% CI: 1.04-1.49), recessive model (OR: 1.39, 95% CI: 1.04-1.86), dominant model (OR: 0.72, 95% CI: 0.56-0.93), homozygote model (OR: 1.78, 95% CI: 1.09-2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07-1.49). No publication bias was found in the meta-analysis. CONCLUSIONS: The meta-analysis suggested -58C allele and 58CC genotype increase the risk of hypertension. Inversely, -58TT genotype decreases the risk of hypertension. PMID- 26884905 TI - Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors. AB - OBJECTIVE: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW MRI) in differentiating malignancies from benign ovarian tumors and a meta analysis to further confirm our results on DW-MRI. METHODS: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. RESULTS: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 +/- 0.269*10(-3) mm(2)/s vs. 0.878 +/- 0.246*10(-3) mm(2)/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. CONCLUSIONS: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID- 26884906 TI - Protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells. AB - Ginsenoside Rg2 is one of the major active components of ginseng and has many biological activities. This study aimed to investigate the protective effects of ginsenoside Rg2 against H2O2-induced injury and apoptosis in H9c2 cells. The results showed that pretreatment with ginsenoside Rg2 not only increased cell viability, but also decreased lactate dehydrogenase (LDH) release. Ginsenoside Rg2 inhibited the decrease of SOD, GSH-PX activities and the increase of MDA content induced by H2O2. Meanwhile, the levels of ROS generation and cardiomyocyte apoptosis in ginsenoside Rg2 group significantly reduced when compared with the model group. Western blot analyses demonstrated that ginsenoside Rg2 up-regulate level of Bcl-2 expression and down-regulate levels of Bax, Caspase-3, -9 expression. These findings indicated that ginsenoside Rg2 could protect H9c2 cells against H2O2-induced injury through its actions of anti oxidant and anti-apoptosis. PMID- 26884907 TI - Laparoscopic treatment for retroperitoneal hyaline-vascular type localized Castleman's disease (LCD) in the iliac vessel region. AB - To improve the understanding, diagnostic levels, and therapeutic levels of retroperitoneal hyaline vascular type LCD in the iliac vessel region. Diagnostic and therapeutic processes of 4 patients with retroperitoneal LCD in the iliac vessel region were retrospectively analyzed. The median ages of the research patients was 31.3 years old, Pelvic vascular dual-source computed tomography (CT) indicated an abnormal pelvic irregular cloddy intensity shadow with heterogeneous densities and punctate calcified lesions. The enhanced scanning showed significantly enhanced lesions and multiple tortuous vascular images inside and around the lesions. Patients' preoperative diagnoses were all "pelvic mass with unknown characteristics", and retroperitoneal masses were successfully stripped off after the laparoscopic surgery. Intra operative findings indicated 1 mass located at the left obturator nerve, 1 at the left internal iliac artery, and 2 at the right external iliac artery. The postoperative pathological reports suggest a diagnosis of Castleman's disease. Retroperitoneal LCD in the iliac vessel region is generally asymptomatic. Preoperative imaging data may help with the diagnosis, but a confirmed diagnosis depends on the results of the pathological examination. Iliac artery embolization is performed prior to laparoscopic mass stripping if the masses have abundant blood supply, while lymphadenectomy is also applied to those with enlarged lymph nodes. PMID- 26884908 TI - Hypoxia/lncRNA-AK123072/EGFR pathway induced metastasis and invasion in gastric cancer. AB - OBJECTIVE: To investigate the role of long noncoding RNAs (lncRNAs) in hypoxia induced gastric cancer (GC) metastasis and invasion. METHODS: We investigated the differentially expressed lncRNAs resulting from hypoxia-induced GC and normoxia conditions using microarrays and validated our results through real-time quantitative polymerase chain reaction. The role of the targeting lncRNA was further detected by in vivo and in vitro assays. RESULTS: We found an lncRNA, AK123072, which was up-regulated by hypoxia. AK123072 was frequently up-regulated in GC samples and promoted GC migration and invasion in vivo and in vitro. Furthermore, AK123072 could mediate the metastasis of hypoxia-induced GC cells. Next, we identified EGFR, which was a metastasis-related gene regulated by AK123072. In addition, we found that the expression of EGFR was positively correlated with that of AK123072 in the clinical GC samples used in our study. Furthermore, we found that the EGFR gene CpG island methylation was significantly increased in GC cells depleted of AK123072. Intriguingly, EGFR expression was also increased by hypoxia, and EGFR up-regulation by AK123072 mediated hypoxia induced GC cell metastasis. CONCLUSION: Our results identified hypoxia/lncRNA AK123072/EGFR pathway in gastric cancer pathogenesis and this might help in the development of new therapeutics in clinics. PMID- 26884909 TI - Experimental study on apoptosis of TNFR1 receptor pro-endothelial progenitor cells activated by high glucose induced oxidative stress. AB - OBJECTIVE: To investigate whether high glucose in vitro activating TNFR1 and further promote rat marrow endothelial progenitor cells (EPCs) apoptosis. METHODS: Rat morrow endothelial progenitor cells were cultured and identified by Confocal Microscopy; then were treated with high glucose (5.5, 15, 30, 60 mmol/L), mannitol (15, 30, 60, 90 mmol/L), high glucose + Tempol and high glucose+ MAB430. Apoptosis rate of the above cells were detected by flow cytometry. ROS and MDA level and anti-O2- were detected by colorimetric technique; the expression level of TNFR1 induced signal pathway related proteins were detected by Western blotting. RESULTS: High glucose can induce endothelial progenitor cells apoptosis, which is mostly in the later stage (72 h-96 h) instead of the earlier stage (24 h-48 h); high glucose can also induce oxidative stress reaction and the produces ROS and MDA increase significantly in the later stage (after 72 h), but anti-O2- decrease significantly. TNF apoptosis signal pathway related protein expression level not increase in the earlier stage (before 24 h) but increase significantly in the later stage (after 72 h). Tempol and MAB430 down-regulate TNF apoptosis signal pathway related protein expression and reduce EPCs apoptosis. CONCLUSION: High glucose activates the TNFR1 of TPCs through oxidative stress reaction and further induces cell apoptosis. PMID- 26884910 TI - Gene gun transferring-bone morphogenetic protein 2 (BMP-2) gene enhanced bone fracture healing in rabbits. AB - PURPOSE: Transferring the bone morphogenetic protein 2 (BMP-2) genes into the tissues or cells can improve the bone healing of the fracture has been widely accepted. We evaluated the efficiency of using gene gun to transfer the BMP-2 gene thereby affected the healing of a fractured bone. METHODS: The vector coding for BMP-2 was constructed by a non-replicating encephalo-myocarditis virus (ECMV) based vector. The segmental bone defect (1.5 cm) model was created by a wire-saw at the middle part of the radius bone of the New Zealand white rabbits. Then either BMP-2 gene or control vector without BMP-2 gene was injected into the tissues around the fracture site. Healing of the defects was monitored radiographically for 9 weeks, bone consolidation was determined by the Lane Sandhu score pre- and post-operatively, which can evaluated bone formation, bone connect and bone plasticity. RESULTS: The radiographic score and bone consolidation rates were significantly higher in animals injected with BMP-2 gene group as compared with control vector-injected animals (P<0.05). The control group still showed no radiological signs of stable healing. Western-blot and RT PCR showed BMP-2 expression was significant increase in the tissues around the site of osseous lesions in comparison with the control vector-injected animals (P<0.05). CONCLUSIONS: Our results suggested that BMP-2 gene transferred by gene gun could increase the expression of BMP-2 protein and improved the bone callus formation therefore shortened the time of bone defect healing. PMID- 26884911 TI - Effects of microRNA-139 on myocardial cell injury induced by oxidative stress. AB - OBJECTIVE: This study aims to explore the effects of miR-139 on myocardial cell injury induced by oxidative stress and its mechanisms. METHODS: H9c2 cells were used in this study. They were divided into control group, H2O2 group, H2O2+miR 139-5-p NC group and H2O2+miR-139-5-p mimics group. Cell activity was detected by MTT method. ROS level was detected by DCFH-DA probe method. MDA and SOD levels and Caspase 3 activity were detected by spectrophotometry. The cell apoptosis was detected by Hoechst 33342 and Annexin V-FITC/PI staining methods. The expression levels of AKT, GSK-3beta, Bax and Bcl-2 were determined by Western blotting methods. RESULTS: It showed that the activity of H9c2 cells decreased with the increase of the dose of H2O2. The activity of miR-139-5-p in H9c2 cells decreased after treatment of H2O2 for 6 h (P<0.01). Compared with control group, cell activity in H2O2 group and H2O2+miR-139-5-p NC group decreased (P<0.01), ROS fluorescence intensity increased (P<0.01), MDA content increased (P<0.01), SOD content decreased (P<0.01), apoptosis degree, Caspase 3 activity and Bax levels increased (P<0.01), Bcl-2, AKT and GSK-3beta decreased (P<0.01). However, they were opposite in H2O2+miR-139-5-p mimics compared with H2O2 group and H2O2+miR 139-5-p NC group. CONCLUSIONS: miR-139-5-p expressed low in oxidative stress of H9c2 cells induced by H2O2 and the oxidative stress injury could be inhibited after increasing the expression of miR-139-5-p, which could be related with the elimination of intracellular oxidative stress products and the resistance to apoptosis through AKT/GSK-3beta signaling pathway. PMID- 26884912 TI - Effects of alpha-zearalanol on spermatogenesis and sex hormone levels of male mice. AB - AIMS: To investigate the mechanisms of alpha-zearalanol (Zeranol)-induced male reproductive toxicity, the effects of Zeranol on spermatogenesis and sex hormone levels of male mice were studied. METHODS: Forty healthy sexually mature male Kunming mice were randomly divided into four groups. The mice were mock-treated or treated with Zeranol 25, 50 or 100 mg/kg via oral gavage for 35 days. The epididymal sperms were counted and their morphology and motility were analyzed. The testicles were examined by light and electron microscopy. The levels of serum/testicular testosterone (T), serum follicle stimulating hormone (FSH) and serum luteinizing hormone (LH) were determined by radioimmunoassay. RESULTS: Zeranol decreased the epididymal sperm count and sperm motility in a dose depend manner. While there were not significant differences in the sperm malformation rates between the Zeranol treated groups and the control group. Furthermore, Zeranol could decrease the weight and the organ coefficient of the seminal vesicles and the testicles and lead to significant pathological changes of the testicles. Zeranol could also decrease the levels of serum T, FSH, LH as well as the levels of testicular T of male mice. CONCLUSIONS: Zeranol induced reproductive toxicity in adult male mice. It could damage spermatogenesis via its direct effects on the testicles and interfere with sex hormone levels of male mice through its effects on the hypothalamic-pituitary-testicular axis. PMID- 26884913 TI - Overexpression of STAT3/pSTAT3 was associated with poor prognosis in gastric cancer: a meta-analysis. AB - Signal transducer and activator of transcription 3 (STAT3) and phospho-STAT3 (pSTAT3) play important roles in the development of gastric cancer. STAT3 is often associated with cell survival, proliferation, and transformation. The prognostic value of STAT3/pSTAT3 in patients with gastric cancer remains controversial in numerous published studies. The aim of this study was to summarize recent findings relevant to the prognostic role of STAT3 and pSTAT3 in patients with gastric cancer. A meta-analysis was performed by searching Web of Knowledge, EMBASE, and PubMed to identify studies on the prognostic impact of STAT3/pSTAT3 in gastric cancers in August 2014. In all, 10 studies were included in the analysis. Data were collected for comparing survival rates in patients with high STAT3 levels compared to those with low levels. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Sensitivity analysis was conducted, and publication bias was evaluated. Eventually, 1667 cases of gastric cancer were subjected to the final analysis. Among patients with gastric cancer, poor survival was predicted by higher expressions of STAT3 (HR=2.30; 95% CI=1.13-4.68; P=0.02) and pSTAT3 (HR=1.75; 95% CI=1.17-2.61; P=0.006). Moreover, overexpression of STAT3 was associated with poor tumor stage. Additionally, our analysis did not show any statistically significant effect of publication bias regarding STAT3 or pSTAT3. The results of this meta-analysis demonstrated that overexpression of STAT3 and pSTAT3 was associated with poor prognosis in gastric cancer. PMID- 26884915 TI - Bisphenol a influences blastocyst implantation via regulating integrin beta3 and trophinin expression levels. AB - OBJECTIVE: This study is to investigate effects of bisphenol A (BPA) on the blastocyst implantation in endometrium. METHODS: Pregnant mice were orally administered with BPA. Implantation sites were examined, and serum estrogen level was assayed with ELISA. Protein expression levels were detected with immunohistochemistry and immunofluorescence staining. RESULTS: High doses (400 and 600 mg/kg/day) of BPA remarkably reduced the implantation sites in the pregnant mice. No significant differences were observed in the serum estrogen level across the groups. Moreover, high doses (400 and 600 mg/kg/day) of BPA significantly declined the expression level of endometrial estrogen receptor alpha (ERalpha) in the pregnant mice. In addition, high doses (400 and 600 mg/kg/day) of BPA significantly declined the expression levels of integrin beta3 and trophinin in the endometrium and blastocysts. CONCLUSION: BPA declines ERalpha expression in endometrium, and inhibits adhesion protein expression in endometrium and blastocysts, causing the adhesion failure of blastocyst implantation. PMID- 26884916 TI - T1 finite element model of Kummell's disease shows changes in the vertebral stress distribution. AB - The aims of this study were to develop a finite element model of delayed post traumatic vertebral osteonecrosis, analyze its effect on the vertebral stress distribution, and provide experimental evidence for osteonecrosis as a risk factor for loss of the vertebral corrective angle. Three-dimensional reconstruction was performed on CT data of the lumbar vertebrae from a 29-year old male without spinal lesions to develop a normal L1-L3 vertebral model and a model with post-traumatic vertebral osteonecrosis at level L2. Vertebral flexion, extension, and lateral bending were simulated using computer software to determine the stress distribution in the cortical and cancellous bone in the two models and the changes in the vertebral stress distribution with the size and location of the cavity. Simulation of a vertebral cavity tended to increase the Von Mises equivalent stress in the vertebral cancellous bone and reduce the equivalent stress in the cortical bone, while the vertebral equivalent stress displayed a reverse distribution. The equivalent stress was increased in both the cancellous and cortical bones with increasing cavity volume, and the equivalent stress in the cortical bone was always smaller than that in the normal vertebrae. Placing the cavity close to the endplate of the vertebrae tended to cause stress concentrations in the cancellous bone around the endplate. The cancellous bone with post-traumatic osteonecrosis tended to experience greater Von Mises equivalent stress than the normal vertebrae. Differences in the cavity volume and location may result in a more severe abnormal stress distribution. PMID- 26884914 TI - Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta Analysis. AB - BACKGROUND: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. METHODS: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. RESULTS: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = 0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-alpha [SMD = -0.61; 95% CI: 0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. CONCLUSION: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion. PMID- 26884917 TI - Application of contrast-enhanced ultrasonography and ultrasonography scores in rheumatoid arthritis. AB - OBJECTIVE: To investigate diagnostic value of ultrasonography scores (US) and contrast-enhanced ultrasonography (CEUS) in evaluating rheumatoid arthritis (RA) activity. METHODS: 39 patients with RA were included and the metacarpophalangeal, proximal interphalangeal, wrist, elbow and knee joints of them were examined by high frequency ultrasound. The severe joints and the related indexes (synovial thickness, synovial blood flow, joint effusion and bone erosion) were exposed. Then scores (0~3) were obtained and the sum was calculated. For 12 patients of the 39, 2.4 ml SonoVue was intravenously injected with observation of synovial enhancing. ROIs time-intensity curve (TIC) was obtained and the parameters including area under curve (AUC), peak intensity (PI) and time to peak (TTP) were analyzed. For 39 patients, the relationships among each parameters, ultrasonography scores, DAS28 scores and biochemical examinations (ESR, CRP, RF, anti-CCP) were analyzed. RESULTS: The US were significantly correlated with DAS28 Scores (r=0.823, P<0.01=. The correlation between US and CRP was better than that between DAS28 scores and CRP (rUS =0.692, rDAS28=0.526, P<0.01). The synovial thickness in US were correlated with DAS28 Scores and biochemical examinations (ESR, CRP) (rDAS28=0.852, rESR=0.779, rCRP=0.587, P<0.01. The AUC and PI in CEUS were significantly correlated with US (rAUC=0.832, rPI=0.809, P<0.01=. The correlations among AUC, PI and ESR were better than that between US and ESR (rAUC=0.907, rPI=0.851, rUS=0.836, P<0.01=. The correlations among AUC, PI and CRP were better than that between US and CRP (rAUC=0.855, rPI=0.854, rUS=0.692, P<0.01. CONCLUSIONS: US was almost identical with DAS28 Scores and biochemical examinations (ESR, CRP) in diagnosis of RA activity, while CEUS was almost identical with DAS28 Scores and biochemical examinations (ESR, CRP). In diagnosis of RA, US may be better than DAS28 Scores, while CEUS better than US. Both of them were useful for evaluation of RA activity. PMID- 26884918 TI - Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC. AB - TNFalpha played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFalpha agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFalpha, the potencies of different anti-TNFalpha agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFalpha for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFalpha was first established by conventional transfection method, the expression of transmembrane TNFalpha was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFalpha reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFalpha, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFalpha neutralizing assay. PMID- 26884919 TI - Live and heat-killed probiotic: effects on chronic experimental colitis induced by dextran sulfate sodium (DSS) in rats. AB - Although a series of studies have shown that VSL#3 (L plantarum, L Bulgaricus, L casei and L. acidophilus, B breve, B longum and B infantis and S salivarius subspecies thermophilus) can exert therapeutic effects on colitis, whether heat killed VSL#3 also can exert similar effects has never been tested. The aim of the study was to investigate whether heat-killed VSL#3 exert therapeutic effects in chronic experimental colitis by inhibiting STAT3 pathway. Chronic experimental colitis was induced by dextran sulfate sodium (DSS) in rats. Rats underwent gavage once daily for seven days with heat-killed VSL#3 (0.6 g/kg/day). The disease activity index (DAI), histological score, colon length and myeloperoxidase (MPO) activity was observed. Expression of inflammatory related mediators (STAT3, P-STAT3) and cytokines (IL-6, IL-23) in colonic tissue were detected. The results showed that live and heat-killed VSL#3 have identical anti inflammatory effects by the assessed DAI, colon length, histological score and MPO activity. Live and heat-killed VSL#3 results in reduced IL-6, IL-23, STAT3 and P-STAT3 expression in colonic tissue. Heat-killed VSL#3 have showed significant anti-inflammatory effects by suppressing STAT3 pathway. PMID- 26884920 TI - Nicotinamide improves sevoflurane-induced cognitive impairment through suppression of inflammation and anti-apoptosis in rat. AB - Nicotinamide is amide form of vitamin B3, participate in oxidation-reduction reaction, and it plays an important role in the maintenance of normal life activities in cells; it has broad application prospects in the treatment of heart blood-vessel disease, respiratory disease, type 1 diabetes and inflammatory autoimmune diseases. Thus the present study aimed to identify whether the nicotinamide improves sevoflurane-induced cognitive impairment and its potential mechanisms in rat. Firstly, Male Sprague-Dawley rats were induced by 2.1% sevoflurane for 6 h. Protective function of nicotinamide on cognitive impairment was evaluated using Morris water maze test in the rats. Next, NF-kappaB and caspase-3 activities, and p53, Bax and Bcl-2 protein expression was executed using commercial kits and Western blot analysis, respectively. Preconditioning with nicotinamide could improve cognitive impairment in the rats. Administrate of nicotinamide suppressed the activation of NF-kappaB and caspase-3, reduced the protein expression of Bax, and promoted Bcl-2 protein expression in rats. The present results suggested nicotinamide improves sevoflurane-induced cognitive impairment and has an anti-inflammatory and anti-apoptotic effect against sevoflrane-induced damages. PMID- 26884921 TI - Phase-contrast imaging with synchrotron hard X-ray of micro lesions of the cartilage of the femoral head in rabbits. AB - BACKGROUND: To observe micro lesions on the cartilage of the rabbit femoral head using phase-contrast imaging with synchrotron hard X-ray and to prove that this method can be useful in the study of the degeneration of cartilage. METHODS: New Zealand white rabbits were used in a micro lesion model of rabbit femoral head cartilage. Bilateral femoral heads were excised from rabbits, and micro lesions were made on one side with a specially made knife with a blade 20 MUm in width. The other femur was left intact to serve as the control. Phase-contrast imaging with synchrotron hard X-ray and conventional X-ray imaging were used to observe the cartilage. Histological changes were investigated using modified Golden tri color staining. RESULTS: Phase-contrast imaging with synchrotron hard X-ray clearly showed the 20 MUm lesions on the cartilage on the heads of rabbit femurs. These lesions were not visible with conventional X-ray imaging. Histological observation confirmed the presence of the microscopic lesions. CONCLUSION: Phase contrast imaging with synchrotron hard X-ray can detect microscopic lesions on cartilage that cannot be detected by conventional absorption-contrast X-ray. This provides an unequivocal, non-invasive alternative to histological examination in the diagnosis of joint disease. It should be considered a new tool in osteoarthritis and cartilage research. PMID- 26884922 TI - Clinical research of percutaneous bilateral splanchnic nerve lesion for pain relief in patients with pancreatic cancer under X-ray guidance. AB - OBJECTIVE: to observe the therapeutic effects of percutaneous bilateral splanchnic nerves block in patients with intractable pain due to pancreatic cancer. METHODS: twenty-fourpatients (advanced pancreatic cancer) with intractable pain were enrolled in the research. Through approach of the edge of T11 vertebral body with double-needle technique, the researchers carried out the bilateral lesion of the greater and the lesser splanchnic nerve with absolute ethyl alcohol under X-ray guidance. Follow-up was six months. Numerical rating scale (NRS) and quality of life (QOL) were all assessed pre- and post-procedure (1 d, 1 w, 2 w, 1 m, 2 m, 3 m, 4 m, 5 m, 6 m). The daily morphine consumption was recorded. RESULTS: NRS and daily morphine consumption decreased when compared to pre-procedure while QOL increased. These differences were found to be statistically significant (P<0.05). 9 patients suffered from diarrhea temporally and recoveredin one week. CONCLUSION: Percutaneous bilateral splanchnic nerves lesion under X-ray guidancecan treat intractable pain caused by pancreatic cancer and improve patients'life quality with minor complication. PMID- 26884923 TI - A rat model of concurrent combined injuries (polytrauma). AB - Polytrauma, a combination of injuries to more than one body part or organ system, is common in modern warfare and in automobile and industrial accidents. The combination of injuries can include burn injury, fracture, hemorrhage, trauma to the extremities, and trauma to specific organ systems. To investigate the effects of combined injuries, we have developed a new and highly reproducible model of polytrauma. This model combines burn injury with soft tissue and gastrointestinal (GI) tract trauma. Male Sprague Dawley rats were subjected to a 15-20% total body surface area scald burn, or a single puncture of the cecum with a G30 needle, or the combination of both injuries (polytrauma). Unlike many 'double hit' models, the injuries in our model were performed simultaneously. We asked whether multiple minor injuries, when combined, would result in a distinct phenotype, different from single minor injuries or a more severe single injury. There were differences between the single injuries and polytrauma in the maintenance of blood glucose, body temperature, body weight, hepatic mRNA and circulating levels of TNF-alpha, IL-1beta and IL-6, and hepatic ER-stress. It has been suggested that models utilizing combinatorial injuries may be needed to more accurately model the human condition. We believe our model is ideal for studying the complex sequelae of polytrauma, which differs from single injuries. Insights gained from this model may suggest better treatment options to improve patient outcomes. PMID- 26884924 TI - Comparison of the efficacy of tenofovir monotherapy versus tenofovir-based combination therapy in adefovir-experienced chronic hepatitis B patients: a systematic review and meta-analysis. AB - BACKGROUND: Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Tenofovir monotherapy or tenofovir-based combination therapy have achieved promising results in the treatment of chronic hepatitis B patients who failed adefovir therapy. OBJECTIVE: The goal of this study was to assess the efficacy of tenofovir monotherapy compared with tenofovir-based combination therapy for treatment of adefovir-experienced chronic hepatitis B (CHB) patients. METHODS: randomized and non-randomized control trials directly comparing tenofovir monotherapy and tenofovir-based combination therapy were searched in PUBMED, MEDLINE, EMBASE database up to April 30, 2015. The data were analyzed with Review Manager (v.5.3). RESULTS: Seven articles (total of 478 patients) met entry criteria. The results found that the rates of undetectable hepatitis B virus DNA levels (64.7% vs. 68.5%, P = 0.58 for 24 weeks; 71.4% vs. 71.7%, P = 0.76 for 48 weeks; 71.6% vs. 73.0%, P = 0.92 for 96 weeks), alanine aminotransferase (ALT) normalization (72.6% vs. 69.2%, P = 0.46 for 48 weeks; 72.8% vs. 75.0%, P = 0.74 for 96 weeks) and hepatitis Be antigen loss (5.0% vs. 0, P = 0.43 for 48 weeks; 16.5% vs. 12.5%, P = 0.43 for 96 weeks) were not significantly different between the TDF alone and the TDF-based group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups (P = 0.06 for 96 weeks). CONCLUSIONS: TDF monotherapy and TDF-based combination therapy are similarly effective and safe in adefovir-experienced CHB patients after 48 weeks and 96 weeks of antiviral therapy. Nevertheless, large scale randomized control trials should be carried out to elucidate the long-term outcome of TDF treatment. PMID- 26884926 TI - MiR-98 inhibits cell proliferation and invasion of non-small cell carcinoma lung cancer by targeting PAK1. AB - A family of small non-coding RNAs, ~22 nt in length, known as microRNAs (miRNAs), regulating ~30% of all human gene expression, have been reported to be involved in the pathogenesis of a number of types of cancers, including non-small cell carcinoma lung cancer (NSCLC). P21-activated protein kinase 1 (PAK1) is a clinical biomarker of Non-small carcinoma lung cancer. Here, we found that miR-98 is down-regulated, whereas PAK1 is highly expressed in NSCLC tissues and cells. We demonstrated that miR-98 directly targets the 3'UTR of PAK1 and down-regulates its expression at the mRNA and protein level. Also, miR-98 inhibited and PAK1 stimulated proliferation, migration, invasion and apoptosis of NSCLC cells. In agreement, PAK1 over-expression counteracted the inhibitory effect of miR-98. This current study suggests that exogenous miR-98 may serve as novel potential maker for NSCLC therapy. PMID- 26884925 TI - Macroscopic serosal classification of colorectal cancer and its clinical significance. AB - BACKGROUND: Macroscopic serosal classification of gastric cancer has been reported in previous studies, but rarely reported about it of colorectal cancer. The purpose of this study was to propose a macroscopic serosal classification of colorectal cancer and to investigate clinical significance of this classification. MATERIALS AND METHODS: Morphologic features of colorectal cancer were analyzed according to the macroscopic serosal appearance and clinicopathologic characteristics of these patients were retrospectively reviewed. Microscopic serosal structure was compared between different types under light microscope and transmission electron microscope. RESULTS: Macroscopic serosal classification was divided into normal type, reactive type, nodular type and colloid type according to the macroscopic serosal appearance and microscopic structure. There were significant differences in tumor size, tumor gross type, histological type, histological grade, tumor necrosis, pT stage, number of nodes metastasis, lymph node metastasis ratio, pN stage, M stage and peritoneal metastasis between patients with different serosal types. Univariate analysis of prognosis revealed macroscopic serosal classification as one of factors significantly correlated with patient survival. However, multivariate analysis only revealed TNM stage significantly correlated with patient survival, while macroscopic serosal classification did not, maybe due to insufficient samples. CONCLUSIONS: Macroscopic serosal classification of colorectal cancer is preliminarily defined and divided into four types. Different macroscopic serosal types indicate different clinicopathologic features and correlate with prognosis of patients with colorectal cancer, but still cannot be proven as an independent factor. PMID- 26884927 TI - MTHFR gene A1298C polymorphisms are associated with breast cancer risk among Chinese population: evidence based on an updated cumulative meta-analysis. AB - OBJECTIVES: Published studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphisms and breast cancer risk among Chinese population have yielded conflicting results. The purpose of this study was to clarify the association between MTHFR gene A1298C polymorphisms and breast cancer risk among Chinese population. METHODS: Systematic searches were performed through the database of Medline/PubMed, Science Direct, Elsevier, CNKI and Wanfang Medical Online. RESULTS: Overall, a significantly increased risk of breast cancer was observed among the subjects carrying MTHFR gene A1298C AC+CC genotype (odds ratio [OR]=1.05 with 95% confidence interval [CI]: 1.01-1.10) as compared to those carrying AA genotype among total Chinese population. We did not observe any significant association between MTHFR gene A1298C polymorphisms and the risk of breast cancer under the additional genetic models of AC vs. AA, CC vs. AA and C-allele vs. A-allele (OR=1.00 with 95% CI: 0.97-1.02, OR=1.01 with 95% CI: 1.00-1.02 and OR=1.00 with 95% CI: 0.99-1.02, respectively). The cumulative meta-analysis showed similar results. In subgroup analysis, we observed subjects carrying AC+CC genotype had an increased breast cancer risk compared with those carrying AA genotype among the studies of sample size less than 1000. We did not observe any significant association between MTHFR gene A1298C polymorphisms and breast cancer risk in additional subgroup analyses. CONCLUSIONS: Our results suggest that MTHFR gene A1298C AC+CC genotype may be a risk factor for the development of breast cancer among Chinese population. Well-designed studies with a large sample size are needed to further confirm our findings. PMID- 26884928 TI - microRNA-363 plays a tumor suppressive role in osteosarcoma by directly targeting MAP2K4. AB - Abnormal expression of microRNAs plays important functions in osteosarcoma. The aim of this study was to investigate expression, functions and molecular mechanisms of microRNA-363 in osteosarcoma. Quantitative Real-time PCR was used to detect the expression level of microRNA-363 in osteosarcoma tissue samples and cell lines. After transfection, CCK8 assay, cell migration and invasion assay, western blot and Dual-Luciferase report assay were performed in human osteosarcoma cells. According to the results, we found that microRNA-363 was down regulated in osteosarcoma tissues and cell lines. In addition, low expression level of microRNA-363 was associated with tumor size, clinical stage and distant metastasis. Moreover, microRNA-363 targeted MAP2K4 to inhibit osteosarcoma cell growth, migration and invasion. In conclusion, microRNA-363 played a tumor suppressive role in osteosarcoma by directly targeting MAP2K4. These findings indicated that microRNA-363 may have therapeutic value in treating osteosarcoma. PMID- 26884929 TI - Pharmacokinetics in rats and tissue distribution in mouse of magnoflorine by ultra performance liquid chromatography-tandem mass spectrometry. AB - Magnoflorine is one of the most widespread aporphine alkaloids. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of magnoflorine in rat plasma and mouse tissue have been developed and validated. After addition of nuciferine as an internal standard (IS), protein precipitation by acetonitrile methanol (9:1, v/v) was used for samples treatment. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm*100 mm, 1.7 MUm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 342.8->298.2 for magnoflorine and m/z 296.0->265.1 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for magnoflorine in rat plasma and tissue. Mean recoveries of magnoflorine in rat plasma were better than 83.0%. RSD of intra-day and inter-day precision were both less than 9%. The accuracy of the method was between 95.5% and 107.5%. The method was successfully applied to pharmacokinetics and tissue distribution study of magnoflorine. The absolute bioavailability of magnoflorine was reported as 22.6%. The magnoflorine underwent a rapid and wide distribution to tissues; the level of magnoflorine in liver is highest, then followed by heart, spleen and lung. Based on tissue distribution data, a back-propagation artificial neural network (BP-ANN) method was developed and it could be used to predict the concentrations of magnoflorine in tissues. PMID- 26884930 TI - Mas-related G-protein-coupled receptor c agonist bovine adrenal medulla 8-22 attenuates bone cancer pain in mice. AB - OBJECTIVES: The aim of this study is to investigate the effects of Mas-related G protein-coupled receptor C (MrgC) agonist bovine adrenal medulla 8-22 (BAM8-22) on bone cancer pain and mirror-image pain. METHODS: Bone cancer pain was induced by intramedullary injection of NC2472 fibrosarcoma cells in the mice. BAM8-22 and/or anti-MrgC antibody were injected intrathecally at day 14 after bone cancer induction and their effects on pain behaviors were detected. The pain behaviours were assessed by the number of spontaneous foot lifts and paw withdrawal mechanical threshold (PWMT) tests. MrgC expression was detected using western blot analysis and immunofluorescence assay. RESULTS: There were increased bone cancer pain and mirror-image pain in the tumor-bearing mice while not in the sham treated mice. BAM8-22 attenuated bone cancer pain in mice dose dependently with the highest effects at 2 hr after BAM8-22 administration, and anti-MrgC antibody reversed the effects of BAM8-22. However, intrathecal administration of BAM8-22 did not affect the mirror-image pain. Furthermore, BAM8-22 stimulated the expression of MrgC in the spinal dorsal horn. CONCLUSIONS: MrgC agonist BAM8-22 could attenuate bone cancer pain in mice. This study may provide a novel strategy for the treatment of bone cancer pain. PMID- 26884931 TI - Icariin has synergistic effects with methylprednisolone to ameliorate EAE via modulating HPA function, promoting anti-inflammatory and anti-apoptotic effects. AB - BACKGROUND: High-dose methylprednisolone (MP) is a clinically recommended therapeutic regimen for Multiple Sclerosis (MS), whereas some dreadful complications induced by it remain inevitable. Studies implied that estrogens might play neuroprotective and anti-inflammatory roles in EAE and MS and promote glucocorticoid efficacy. Icariin (ICA), a primary active component of Epimedium extracts, also possesses neuroprotective and estrogen-like effects with less adverse complication than estrogen. However, rare study focuses ICA's effects on MS or EAE. OBJECTIVE: Our purpose is to determine whether ICA has synergistic effects with MP in treating EAE and explore the possible mechanisms. METHODS: C57BL/6 EAE mice were received different dose of ICA combined with MP and single MP treatment. Then, the clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT), Adrenocorticotropic Hormone (ACTH) concentrations were analyzed. Western blot and Flow Cytometry were used to investigate the expression of glucocorticoid receptor (GR) and cell apoptosis. RESULTS: ICA has cooperative effects with MP in decreasing serum IL-17 and CORT concentrations, up-regulating the expression of GR in cerebral white matter and attenuating the cell apoptosis in spinal cord, especially high-dose ICA combined with MP. CONCLUSION: ICA has synergistic effects with MP to ameliorate EAE via modulating hypothalamic pituitary-adrenal (HPA) function, promoting anti-inflammatory and anti-apoptotic effects. ICA could be considered as a promising therapeutic option for MS. PMID- 26884932 TI - Levofloxacin increases apoptosis of rat annulus fibrosus cells via the mechanism of upregulating MMP-2 and MMP-13. AB - Levofloxacin was previously reported to induce apoptosis of rat annulus fibrosus (AF) cells by upregulating active caspase-3 and matrix metalloproteinase (MMP)-3 expression in vitro. However, the effects of levofloxacin on rat AF cells, as well as the related mechanism, have not been revealed completely. The purpose of this study was to further explore the changes in extracellular matrix and MMPs of rat AF cells based on levofloxacin-induced apoptosis. AF cells isolated from rat AF regions were cultured in monolayers and treated with levofloxacin in a dose- and time-dependent manner. To determine the cytotoxic effects of levofloxacin, inverted phase-contrast microscopy was used to perform morphological observation of apoptotic cells. The mRNA expression levels of MMP-2, -9 and -13 were quantified by reverse transcription and real-time quantitative polymerase chain reaction (RT-qPCR). Protein level of MMP-2 and MMP-13 were determined by western blot. The results showed that levofloxacin induced marked AF cell apoptosis, which was observed by inverted phase-contrast microscopy, and indicated by the increased expression of active caspase-3. Both RT-qPCR and western blot revealed that MMP-2 and MMP-13 expression were upregulated by levofloxacin treatment in a time- and dose-dependent manner. Moreover, cellular binding to type I collagen was found to be decreased by levofloxacin. In conclusion, the results above suggest that the possible cytotoxic effects of levofloxacin on AF cells in vitro may be attributed to the decreased cell binding to type I collagen and up regulated expression of MMP-2 and MMP-13. PMID- 26884933 TI - Lentiviral vector PLV-PI3KCG gene transfer inhibits hypoxic cardiomyocytes apoptosis. AB - The PI3K/Akt signal pathway was suggested to be associated with apoptosis. However, it was still unclear whether activated PI3K/Akt signaling pathway could inhibit hypoxic cardiomyocytes apoptosis. In this research, the recombinant PI3KCG lentiviral vector plasmid (PLV-PI3KCG) was constructed and transfected into neonatal rat hypoxia/reoxygenation (H/R) injury cardiomyocytes models which were randomly divided into five groups as the normal control group, H/R group, HR empty plasmid group (HRE group), HR PLV-PI3KCG transfection preconditioning group (HRP group), and HR PLV-PI3KCG transfection + LY294002 group (HRPL group). Compared with the H/R, HRE and HRPL groups, the cardiomyocytes beat frequency and survival rate in the HRP group were significantly increased (P<0.05) and the released LDH were significantly decreased (P<0.05). The Bcl-2/Bax ratio was significantly lower in H/R, HRE and HRPL groups than that in HRP group (P<0.05). Activated PI3K/Akt signaling pathway could play a protection role in the cardiomyocytes H/R injury process which could be inhibited by LY294002. PMID- 26884934 TI - Biomechanical properties of the sciatic nerve following repair: effects of topical application of hyaluronic acid or tacrolimus. AB - Recovery following nerve repair can be evaluated based on electrophysiological and morphological assessments of biomechanical properties. This study compared the effects of topical hyaluronic acid (HA), tacrolimus (FK-506) or saline administration on the biomechanical properties of the sciatic nerve at 12 weeks after nerve repair. MATERIALS AND METHODS: Eighteen male European rabbits (Oryctolagus cuniculus) (weight from 2.5 to 3 kg) were randomly assigned to one of the following experimental groups (six animals per group): Saline, HA, or FK 506. The non-transected left leg was used as a control group (eighteen sciatic nerves). Biomechanical assays were performed and statistically analyzed. RESULTS: The average maximal load, elastic limit load, maximal stress, and elastic limit strain of the control group were significantly different (P<0.001) from those of all three experimental groups. Moreover, the other examined parameters (i.e., maximal displacement, elastic limit stress, and maximal strain) were significantly different between the control group and all three experimental groups (P<0.0001). However, no significant differences in any of the biomechanical parameters were observed between the experimental groups (P>0.05). At 12 weeks after nerve repair, Saline, HA, and FK-506 groups displayed average maximal stress values that were 72.6%, 77.38%, and 73.8% of those in the control group (100%), respectively. CONCLUSION: The biomechanical properties of the HA and FK-506 groups were similar to those of the saline group at 12 weeks after nerve repair. PMID- 26884935 TI - Expression and significance of Nodal in human cancers: a meta-analysis. AB - Cancer is a global and growing problem. Nodal, which has been showed to be involved in occurrence and development of cancers, is an important embryonic morphogen. The aim of this study was to evaluate the significance of Nodal expression in human cancers based on the published related articles. Online databases were searched to retrieve relevant articles published between 2000 and 2015. The odds ratio (OR) with its 95% confident intervals (CI) were employed to calculate the strength of significance. Finally, a total of 11 articles were screened out, including 801 cancer patients and 372 healthy controls. Nine kinds of cancers were contained, and Nodal was detected in 56.7% of all participants (665/1173). Overall, our result found that Nodal was highly expressed in cancer patients than that in healthy controls, indicating that Nodal expression was significantly associated with cancers progression (OR=21.72, 95% CI=9.94-47.46, P<0.00001). Subgroup analysis showed that Nodal expression was significantly corrected with high WHO grade of human cancers (III+IV versus I+II: OR=2.46, 95% CI=1.63-3.71, P<0.00001). This significant relationship was also found in tumor size, differentiation degree, not observed in gender, age and lymphatic metastasis status of patients with all studied cancers in this meta-analysis. In conclusion, our results demonstrated that Nodal might be implicated in cancer progression, suggesting that it was a potential biomarker and therapeutic target for cancers. PMID- 26884936 TI - The association between rs9642880 gene polymorphism and bladder cancer risk: a meta-analysis. AB - Previous studies had researched the relationship between rs9642880 gene polymorphism and bladder cancer risk, but the results remained unclear. The comprehensive meta-analysis was performed to clarify this possible association. Relevant articles were searched from Pubmed, Embase and web of science. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to assess the strength of the association. The assessment of publication bias was conducted by Begg's funnel plots and Egger's regression test. A total of 7 casecontrol studies involving 4072 cases and 4898 controls were included in our study. Overall, an obvious relationship between rs9642880 polymorphism and increased risk of bladder cancer were detected in all models. Besides, the positive results were observed among both Caucasians and Asians when stratified by ethnicity. Moreover, when stratified by genotyping method, the significant results were detected in all genotyping methods except Sequenom. In addition, in the subgroup analysis by source of control, significant results were detected in both population and hospital based controls. This present meta-analysis with accurate and reliable results indicated that the T allele of SNP rs9642880 confers susceptibility to bladder cancer in both Asian and Caucasian populations. PMID- 26884937 TI - Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice. AB - Ascorbic acid (AA) has been shown to exert beneficial effects, including mitigating oxidative stress and inhibiting inflammation. However, the preventative effect of vitamin C in chronic inflammatory diseases such as inflammatory bowel disease (IBD) remains unclear. In our study, we investigated the anti-inflammatory effects of AA and possible mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Male C57BL/6 mice were randomly divided to three groups: control group, DSS group, and DSS plus ascorbic acid treated group. Several clinical and inflammatory parameters as well as oxidative stress were evaluated. The results demonstrated that ascorbic acid significantly reduced clinical signs, inflammatory cytokines, myeloperoxidase (MPO) and malonaldehyde (MDA) activities, whereas the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased in DSS-induced mice. In addition, ascorbic acid was capable of inhibiting NF-kappaB, COX-2 and iNOS expression in the colonic. Taken together, these findings suggest that ascorbic acid contributes to the reduction of oxidative stress and inflammatory response in DSS-induced colitis and exerts the potential to prevent and clinical treatment of inflammatory bowel disease. PMID- 26884939 TI - miRNA-101 inhibits ovarian cancer cells proliferation and invasion by down regulating expression of SOCS-2. AB - OBJECTIVE: To investigate the expression of miRNA-101 in normal and malignant ovarian tissues and cells as well as its impact on the proliferation and invasion of human ovarian cancer H08910 and SKOV3 cell lines. METHODS: Real time polymerase chain reaction (RT-PCR) was employed to detect the miR-101 and SOCS-2 expression in 20 separate ovarian cancer tissues and para-carcinoma tissues, human ovarian cancer cells (H08910 and SKOV3) and normal human ovarian epithelial cells (HUM-CELL-0088). After H08910 and SKOV3 ovarian cancer cells were respectively transfected with miR-NC (H08910/NC and SKOV3/NC) and miR-101 (H08910/miR-101 and SKOV3/miR-101), Western Blot was employed to detect the SOCS 2 expression in transfected cells. CCK-8 and clone formation and Transwell assays were employed to determine the proliferation and invasion ability of wild type and transfected ovarian cancer cells. RESULTS: The expression of miR-101 in ovarian cancer tissues and cells was significantly lower than that in para carcinoma tissues (t=19.12, P=0.002) and normal human ovarian epithelial cells (HUM-CELL-0088) (F=14.37, P=0.000), respectively. In contrast, the SOCS-2 expression in ovarian cancer tissues and cells was significantly higher than that in para-carcinoma tissues (t=25.03, P=0.000) and HUM-CELL-0088 cells (F=14.9, P=0.000) by Western Blotting analysis, respectively. Compared with wild type and empty vector transfected cells, the expression of SOCS-2 was significantly decreased in miR-101 transfected H08910 (t=10.9, P=0.001) and SKOV3 cells (t=21.03, P=0.000). The results of CCK-8, clone formation and Transwell assays revealed that the proliferation and invasion ability of ovarian cancer cells was markedly inhibited by the transfection of miR-101. CONCLUSION: MiR-101 was validated to be reduced and SOCS-2 expression increased in ovarian cancer tissues and cells. The over expression of miR-101 can remarkably reduce the in vitro proliferation and invasion ability of ovarian cancer cells through the down regulation of SOCS-2. PMID- 26884938 TI - Safflower extract inhibiting apoptosis by inducing autophagy in myocardium derived H9C2 cell. AB - The Heart failure (HF) is considered as the end-stage of various heart disease and associated with high mortality globally. Progressive loss of cardiac myocytes via apoptosis is considered as the most important factor for HF pathology. In this study, we demonstrated that Safflower extract was able to inhibitthe apoptosis inducted by Angiotensin II (AngII) in a ratmyocardium derived cell line H9C2. Further examination of LC-3II conversion and autophagosome formation suggested Safflower extract induced autophagy in treated cell. Inhibition of Safflower extract induced autophagy by 3-methyladenine (3MA) abolished anti apoptotic function of Safflower extract, while application of autophagy stimulator Rapamycin in H9C2 inhibited apoptosis as well. Moreover, treatment of H9C2 cell with Safflower extract also inhibited expression of pro-apoptotic genes BAD and Bax. In conclusion, our data indicated that Safflower extract inhibit apoptosis via inducing autophagy in myocardium cell and demonstrated the potential as novel therapeutic drug for Heart failure. PMID- 26884940 TI - Subconjunctival injection of in vitro transforming growth factor-beta-induced regulatory T cells prolongs allogeneic corneal graft survival in mice. AB - This study is to investigate the effect of subconjunctival injection of in vitro induced regulatory T cells (iTregs) on the survival of corneal allografts. iTregs were expanded by culturing CD4(+)T cells with TGF-beta in vitro. Foxp3, LAP and GARP were analyzed and the suppression ability of iTregs was assayed by co culturing with effective T cells. Allogeneic transplantations in mice were modeled and randomly classified into PBS control, iTregs and TA groups. The allografts were observed for 60 days. CD25, Foxp3, LAP and GARP in CD4(+)T cells were analyzed on day 21 after the surgery. Inflammatory cells infiltrated in allografts were detected by flow cytometry and histopathological examination. Expressions of Foxp3, GARP and LAP in iTregs were high. iTregs suppressed the proliferation of effective T cells in vitro. The corneal allograft survival time for PBS, iTregs and TA groups was (18 +/- 1.73) days, (38.6 +/- 1.14) days and (60 +/- 0) days, respectively. The corneal allograft survival time in iTregs group was significantly prolonged compared with PBS group (P < 0.05), but shorter than that in TA group (P < 0.05). No significant difference was observed in expressions of CD25, Foxp3, LAP or GARP in CD4(+)T cells (P > 0.05). Finally, CD3(+)CD4(+)T cell infiltration and fewer inflammatory cells were reduced in allografts in iTregs and TA groups compared with PBS group. The survival time of allografts were prolonged in mice after subconjunctival injection of iTregs. Local immune modulation might be involved in the mechanism. PMID- 26884941 TI - The protective effects of total phenols in magnolia officinalix rehd. et wils on gastrointestinal tract dysmotility is mainly based on its influence on interstitial cells of cajal. AB - Magnolia officinalix Rehd. et Wils is a kind of herb which is widely used for gastrointestinal tract mobility disorder in Asian countries. In this study, we investigated whether the total phenols of Magnolia officinalix Rehd. et Wils (TPM) treatment improves gastrointestinal tract dysmobility induced by intraperitoneal injection of atropine (5 mg/kg) in rats. Rats were randomly grouped into three units: TPM-pretreated/atropine-treated group, atropinetreated group and control group. TPM were administrated for 7 days. Gastric residual rate and intestinal transit were measured 20 min after atropine injected, and gastrointestinal hormones (including: gastrin (GAS), motilin (MTL), somatostatin (SS) and p substance (PS) levels in serum were also measured by ELISA kits. The number and distribution of interstitial cells of Cajal (ICCs) in stomach were detected by immunohistochemistry analysis, while c-kit and stem cell factor (SCF) expressions in stomach were also measured by western blotting. We found that TPM pretreatment significantly improved atropine-induced gastric residual rate increase, while had no significantly effects on intestinal transit; it also significantly normalized GAS, MTL and PS serum levels. Atropine-induced ICCs numbers decreased in both sinuses ventriculi and body of stomach, which is improved by TPM pretreatment. Western blotting results showed the expressions of c-kit and SCF were down-regulated after atropine injection, which can be reversed with TPM pretreatment. These results above indicates that TPM treatment can significantly protected atropine-induced gastric dysmoblility, which may owed to its regulation on c-kit/SCF signing pathway. PMID- 26884942 TI - Lower MGMT expression predicts better prognosis in proneural-like glioblastoma. AB - OBJECTIVE: To investigate the expression and significance of MGMT in different molecular subtypes of glioblastoma (GBM), and to evaluate the important role of MGMT and P53 in predicting the prognosis of GBM patients. METHODS: MGMT expression was detected by immunohistochemical staining in 72 cases of GBM which had been classified as three molecular subtypes. The relationship between MGMT and P53, an important molecule for identification of proneural-like GBM, were further analyzed. The association between MGMT and patients' prognosis was analyzed with Kaplan-Meier method, which was further validated by the data from 513 cases of GBM in the TCGA database. RESULTS: MGMT expression was lower in proneural-like subtype in 72 GBM cases (p < 0.001), and was negatively correlated with P53 (r=-0. 6203, p < 0.001). This results was also verified by a validation group of 87 GBM cases (r=-0. 2950, p < 0.001). Interestingly, low expression of MGMT predicted a better outcome in proneurallike subtype or P53 high-expression group (p < 0.05) but not in non-proneural-like subtype and P53 low-expression group. All of these results were verified by the data from TCGA database. CONCLUSION: MGMT can be used as an independent prognostic factor and plays an important role in molecular typing and diagnosis of GBM by combination with proneural-like subtype marker P53. PMID- 26884943 TI - A comparison of general versus regional anesthesia for hip fracture surgery: a meta-analysis. AB - In this study, we aimed to compare the effect of general versus regional anesthesia on postoperative outcomes in patients undergoing surgical repair of hip fracture. Randomized controlled trials, prospective studies and retrospective observational studies were searched in PubMed, Medline and Embase database published between January 2005 and March 2014. The overall outcome was measured by odds ratios (ORs) and risk ratios (RRs) with their corresponding 95% confidence intervals (CIs). A total of 7 trials, involving 36448 patients received general anesthesia and 33952 patients received regional anesthesia, were included in present meta-analysis. We found that the 30-day mortality rate was lower in general anesthesia cases than that in regional cases (5.3% vs. 6.3%). Overall, our results demonstrated that there was no significant difference in 30 day mortality between two types of anesthesia in patients with hip fracture surgery (RR=0.98, 95% CI=0.92-1.04, P=0.48), indicating that types of anesthesia might not be a risk factor for hip fracture surgery. No statistically significant difference was observed in other outcome measures (P>0.05). In conclusion, our results suggested that the choice of anesthesia (general or regional) should be made by the anesthesiologist on an individual basis and based on the patient's medical conditions. Further research is still needed to evaluate the effect of these two anesthesia methods. PMID- 26884944 TI - Interventional effects of da-cheng-qi decoction on enteric nerve system in a rat model of multiple organ dysfunction syndrome. AB - In this study, we investigate the morphologic changes of enteric nerve system (ENS) and the expression of neurotransmitters, acetylcholine (ACh), substance P (SP), vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), in small bowel of rats undergoing multiple organ dysfunction syndrome (MODS). Undergoing MODS, fluorescence integral optical density (IOD) value of enteric nerve fibers were significantly decreased (P<0.05), and the network structure of ENS was destroyed. The expression of ACh, SP, VIP and NOS was inhibited, IOD value of the four neurotransmitters was significantly decreased (P<0.05). After intervention of DCQD, the fluorescence IOD value of enteric nerves were significantly increased (P<0.05), and the network structure of ENS was repaired. The expression of ACh, SP, VIP and NOS was recovered, fluorescence IOD value of the four neurotransmitters was significantly increased (P<0.05). In conclusion, the gastrointestinal motility disorders undergoing MODS may be closely related to the morphology destroy of ENS and down regulation of neurotransmitters (ACh, SP, VIP and NOS) expression. DCQD could promote gastrointestinal motility through protecting the morphology of ENS and up regulation of neurotransmitters (ACh, SP, VIP and NOS) expression. PMID- 26884945 TI - Experimental study of super paramagnetic iron oxide labeled synovial mesenchymal stem cells. AB - To investigate the feasibility and changes of biological characteristics before and after synovial mesenchymal stem cells (SMSCs) labelled by super paramagnetic iron oxide (SPIO). The rabbit SMSCs were isolated, cultured, purified and identified in vitro. After adding the different concentrations of SPIO-labelled liquid, the cells were incubated 24 h in 37 degrees C carbon dioxide incubator. The labeled-cell samples were observed by Prussian blue staining, transmission electron microscope (TEM) and the cell biology before and after the labeling was compared. The blue stained particles could be seen in the cytoplasm; the SPIO label was positive in 95% SMSC cells. With the concentration of the label liquid increasing, the blue-stained cytoplasm became darker. A large number of high electron density particles could be seen in the cytoplasm and in the pinocytosis vesicles by TEM, which suggested SPIO label positive. When the SPIO concentration was (12.5~50) MUg/mL, the differences in cell proliferation and cell viability between the SMSCs after labelling and the SMSCs before labelling were not significant; when the concentration was over 100 MUg/mL, the cell proliferation and cell viability were inhibited. A certain concentration range of SPIO can safely label the rabbit SMSC according to this study, which is important for solving the problem of tracing SMSCs in the joints. PMID- 26884946 TI - Antitumor effects of crocin on human breast cancer cells. AB - Crocin is a chemical extracted from saffron and it is the most important kind of pigment of saffron. It has been proposed as a promising candidate for cancer prevention. In this study, we investigate the growth inhibition and the apoptosis of MCF-7 cells induced by Crocin, and explore the underlying molecular mechanism. We found that Crocin can significantly inhibit the proliferation of MCF-7 cells, and induce their apoptosis through mitochondrial signaling pathways including the activation of Caspase-8, upregulation of Bax, the disruption of mitochondrial membrane potential (MMP), and the release of cytochrome c. The studies showed that Crocin induced apoptosis of MCF-7 cells partially through caspase-8 mediated mitochondrial pathway. Therefore, we postulate that Crocin might have cancer preventive and cancer-therapeutic benefit for human breast cancer. PMID- 26884947 TI - Diosgenin attenuates hepatic stellate cell activation through transforming growth factor-beta/Smad signaling pathway. AB - Activation of hepatic stellate cells (HSC) plays a pivotal role in the development of hepatic fibrosis. Transforming growth factor-beta1 (TGF-beta1) is considered to be the main stimuli factor responsible for the activation of HSC. Diosgenin is a steroidal saponin found in several plants including Solanum and Dioscorea species, and it inhibited high glucose-induced renal tubular fibrosis. However, the effects of diosgenin against hepatic fibrosis remain elusive. Therefore, in this study, we investigated the effects of diosgenin on TGF-beta1 induced HSCs and elucidate the possible mechanism of its anti-fibrotic effect. Our results demonstrated that diosgenin inhibited TGF-beta1-induced HSC proliferation, reduced the expression of collagen I and alpha-smooth muscle actin (alpha-SMA), as well as the expression of TGF-beta receptor I (TGF-beta RI) and II. Moreover, diosgenin suppressed TGF-beta1-induced phosphorylation of Smad3 in HSCs. In conclusion, our data demonstrate that diosgenin inhibited HSC-T6 cell proliferation and activation, at least in part, via the TGF-beta1/Smad signaling pathway. These results provide that diosgenin may have potential to treat liver fibrosis. PMID- 26884949 TI - Relation between osteonecrosis of the femoral head and PAI-1 4G/5G gene polymorphism: a meta-analysis. AB - OBJECTIVE: The aim of this study was to investigate the association of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene polymorphism and osteonecrosis of the femoral head (ONFH). METHODS: The pooled relative risk ratio (RR) and 95% confidence intervals (95% CI) were calculated using the the RevMan 5.0 software. RESULTS: The present study included 969 patients with ONFH and 419 healthy controls. The Meta analysis results showed: There is association between PAI-1 gene 4G/5G polymorphism and the increasing risk of ONFH (allele model: RR = 1.24, 95% CI = 1.16 ~ 1.33; dominant genetic model: RR = 1.12, 95% CI = 1.05 ~ 1.18). It was found that the association between PAI-1 gene 4 G/5 G polymorphism and the susceptibility of ONFH (P < 0.05) through the comparison of Caucasian population and Asian people according to the analysis of different races. CONCLUSIONS: There is association between PAI-1 gene 4 G/5 G polymorphism and the increasing of the susceptibility of ONFH. PMID- 26884948 TI - KLF15 suppresses cell proliferation and extracellular matrix expression in mesangial cells under high glucose. AB - Excess mesangial extracellular matrix (ECM) and mesangial cell (MC) proliferation is the major pathologic feature of diabetic nephropathy. Kruppel-like factor 15 (KLF15) is a member of the KLF transcription factor family that plays a critical role in regulating renal fibrosis. However, the role of KLF15 in diabetic nephropathy remains poorly understood. This study was conducted to explore the role of KLF15 in the development and progress of diabetic nephropathy in high glucose (HG)-stimulated human MCs. Here, we found down-regulated expression of KLF15 in MCs induced by HG. Overexpression of KLF15 significantly inhibited MCs proliferation and ECM production induced by HG. Moreover, overexpression of KLF15 inhibited HG-induced ERK1/2 phosphorylation in MCs. In summary, our data demonstrate that KLF15 can suppress HG-induced cell proliferation and ECM protein fibronectin expression in human MCs via ERK1/2 MAPK signaling. The results provide evidence that KLF15 might be a potential molecular target for the treatment of diabetic nephropathy. PMID- 26884950 TI - Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta analysis. AB - OBJECTIVE: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. METHODS: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. RESULTS: The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71 1.42). CONCLUSION: For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer. PMID- 26884951 TI - Role of sphingosine 1-phosphate in human pancreatic cancer cells proliferation and migration. AB - Deregulation of production or degradation of sphingosine 1-phosphate (S1P), a bioactive lipid, involves in tumor progression, metastasis and chemoresistance. Since the tumor progression effects of S1P and its mechanism in human pancreatic cancer is not fully understood, we investigated the role of S1P in Capan-1 and Panc-1 cells proliferation and migration. The effects of S1P on proliferation, invasion and migration were studied using MTT and transwell assay, respectively. The concentrations of MMP2 and MMP9 were detected by ELISA assay. Role of S1P on the expressions of tyrosine kinase and cell proliferation related proteins were assessed by western blot. Our results showed that cell proliferation and migration were mediated by low concentration of S1P treatment in both cell lines. In addition, we also investigated another survival mechanism of S1P in cell survival and tumor progression, Src signaling pathway. These results indicated that roles of S1P in tumor progression were S1P receptor-dependent through interaction with Src signaling pathway. In conclude, our data demonstrated the importance of this molecule as a target to design novel anticancer drugs in future through S1P receptors and Src signaling pathway. PMID- 26884952 TI - The association of TGFB1 genetic polymorphisms with high myopia: a systematic review and meta-analysis. AB - OBJECTIVE: The TGFB1 gene is among the most studied genes in high myopia due to its role in scleral remodeling. But reported findings of association on TGFB1 and high myopia are inconsistent. This present study is to evaluate the association of TGFB1 polymorphisms and high myopia. METHODS: A comprehensive literature search was conducted on studies published up to April 5, 2015. Summary odds ratios (ORs) and 95% confidence intervals were analyzed. Heterogeneity across studies was evaluated by Cochran Q statistic test and the I(2) index. Sensitivity analyses were conducted by the approach of one-study remove to assess the influence of single study on the combined effect. RESULTS: Eight studies were included in this study for meta-analysis. Rs1982073 was associated with high myopia in dominant model (OR=1.64; 95% CI=1.04~2.58; P<0.05), heterozygous model (OR=1.54; 95% CI=1.02~2.33; P<0.05), homozygous model (OR=1.90; 95% CI=1.01~3.55; P=0.05) and allelic model (OR=1.36; 95% CI=1.01~1.84; P=0.05). However, there was no statistical significance when Bonferroni correction was considered. Rs4803455 was associated with high myopia in recessive model (OR=0.40; 95% CI=0.25~0.64; P<0.01) and homozygous model (OR=0.42; 95% CI=0.26~0.68; P<0.01). Rs1800469 was associated with high myopia in allelic model (OR=0.78; 95% CI=0.64~0.96; P<0.05). And the associations can withstand Bonferroni correction in models mentioned above when referring to rs4803455 (P<0.01) and rs1800469 (P<0.05). CONCLUSIONS: Meta-analysis of existing data revealed a suggestive association of TGFB1 rs1982073 and rs4803455 with high myopia. PMID- 26884953 TI - Chlamydial plasmid-encoded protein pORF5 induces production of IL-1beta and IL-18 via NALP3 inflammasome activation and p38 MAPK pathway. AB - The pathogenesis of Chlamydia-induced inflammation is poorly understood. pORF5 is the only secreted protein encoded by Chlamydial plasmid. This study aims to investigate the effects of pORF5 on the production of interleukin-1beta (IL 1beta) and interleukin-18 (IL-18) and the underlying mechanisms of these effects. THP-1 (a human acute monocytic leukemia cell line) cells were stimulated by pORF5 with or without pretreatment with Natch domain, Leucine-rich repeat and PYD containing protein 3 (NALP3) siRNA, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) siRNA, cysteine aspartate-specific protease-1 (caspase-1) specific inhibitor and p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. IL-1beta, IL-18 and caspase-1 expression was detected through both ELISA and qRT-PCR. NALP3 and ASC expression was detected by qRT-PCR. The expression of caspase-1 and phosphorylated-p38 MAPK was detected by western blot analysis. pORF5 induced IL-1beta, IL-18, caspase-1 and NALP3 inflammasome expression in THP-1 cells. Caspase-1 inhibitor significantly reduced pORF5-induced IL-1beta and IL-18 expression. The siRNAs for NALP3 inflammasome significantly reduced pORF5-induced IL-1beta, IL-18 and caspase-1 expression. Furthermore, p38 MAPK inhibitor significantly reduced pORF5-induced IL-1beta, IL 18, caspase-1 and NALP3 inflammasome expression. pORF5 could induce production of IL-1beta and IL-18 via NALP3 inflammasome activation and p38MAPK pathway. pORF5 protein might play an important role in Chlamydia pathogenesis. This study provides a new insight into the molecular pathogenesis of Chlamydial diseases. PMID- 26884954 TI - Sulfated modification promotes the immunomodulatory bioactivities of Lyciumbarbarum polysaccharides in vitro. AB - Three kinds of purified Lyciumbarbarum polysaccharides (LBPSs), LBPS30, LBPS70 and total LBPS (LBPSt), were modified using chlorosulfonic acid-pyridine method based on the previous experiment, forming three sulfated LBPS (sLBPS), sLBPSt, sLBPS30 and sLBPS70 respectively. They were characterized by ultrasonic-acidic barium chromate spectrophotometry, infrared (FT-IR) and high performance gel permeation chromatography (HPGPC). The immunomodulatory activity of each kind of LBPSs and sLBPSs was further examined to determine the relationship between the structure and bioactivity, and the sLBPS with the highest activity was selected. The results showed that sulfate contents were 390.67, 542.75 and 291.71 mg/g respectively, with different molecular masses. The appearance of two new characteristic absorption bands at near 1230 and 855, 853 or 808 cm(-1) in FT-IR spectra revealed the success of sulfation. sLBPSt with high molecular weight and moderate sulfate content exhibited the best immunomodulatory activity by promoting lymphopoiesis and T lymphocyte differentiation as well as increasing IL 2, IL-6, IFN-gamma and TFN-alpha production in vitro compared with the inartificial polysaccharides. These results indicated that sulfated modification could be considered as an effective way to enhance immune activity of LBPSs. Furthermore, sLBPSt showed the best performances and would be expected as a new source of immunopotentiator. PMID- 26884955 TI - Correlations of MMP-2 and TIMP-2 gene polymorphisms with the risk and prognosis of gastric cancer. AB - AIM: To investigate the correlations of MMP-2 and TIMP-2 polymorphisms with the risk and prognosis of gastric cancer (GC). METHODS: With an incorporation of 254 GC patients in the case group and 250 healthy subjects enrolled as the control group, this experiment was conducted. Denaturing high performance liquid chromatography method was adopted to detect all genotypes under partial denaturation, haloptype analysis was completed with the Shesis software. Serum MMP-2 and TIMP-2 levels were determined by the immunohistochemical semi quantitative analysis. The follow-up examination was conducted after the patients had completed systemic therapy and discharged. RESULTS: The distribution frequencies of MMP-2-735C/T locus genotypes between groups were compared (P > 0.05). However, the distributions of alleles and genotype frequencies of MMP-2 1306C/T, TIMP-2-303G/A and -418G/C all exhibited statistical difference (all P < 0.05). The gene polymorphism of MMP-2-1306C/T was statistically correlated with the expression of MMP-2 protein (P < 0.05); the same result was also found regarding TIMP-2-303G/A (P < 0.05). The haplotype analysis revealed that the CGC frequency of the case group was apparently higher than that of the control group (P < 0.05), the positive survival rate of CGC was apparently lower than the negative one. CONCLUSION: MMP-2-1306C/T, TIMP-2-303G/A and -418G/C variants might be correlated with GC susceptibility. Serum MMP-2 and TIMP-2 protein levels might be associated with GC susceptibility; Additionally, CGC haplotype might be the risk factor of GC. PMID- 26884956 TI - Evaluation on the immunotherapy efficacies of synthetic peptide vaccines in asthmatic mice with group I and II allergens from Dermatophagoides pteronyssinus. AB - To assess the immunotherapy efficacies of recombinant vaccines containing T-cell epitopes derived from group I and allergens from Dermatophagoides pteronyssinus (Der p1, Der p2). Forty female BALB/c mice were randomized into groups of negative control (PBS group), positive controls (Asthma group), immunotherapy with rDer p1 and rDer p2 protein suspension (rDer p1/rDer p2 group) and specific immunotherapy with fusion peptide T1-8 (T1-8 group). Asthmatic mouse models were initially established with the crude extract from house dust mites (HDM), and PBS models were solely treated with PBS buffer. The two treatment groups were managed with corresponding protein via subcutaneous injection at the back 30 minutes before inhalation sensitization from day 25 to 27. Twenty-four hour following the final inhalation challenge, sera, bronchoalveolar lavage fluid (BALF) and the supernatant of splenocyte cultures (SSCC) were collected in each group of mice. ELISA was used to assay the levels of IFN-gamma, IL-4, IL-10 and IL-17 in the BALF and SSCC, as well as serum levels of specific IgE, IgG1 and IgG2a. The lung tissue sections were stained with haematoxylin and eosin (H&E) for pathological examination. ELISA detection revealed reduced levels of IL-4 and IL-17 in the BALF and SSCC, yet increased levels of IFN-gamma and IL-10, and decreased specific serum IgE and IgG1, yet increased serum IgG2a in T1-8 group and rDer p1/rDer p2 group than asthma group (P<0.05). T1-8 group had lower IL-4 and IL-17 level and higher IFN-gamma and IL-10 level in the BALF and SSCC as well as reduced specific serum IgE and IgG1, yet elevated IgG2a level compared to rDer p1/rDer p2 group (P<0.05). Examination on the lung sections indicated significantly abated pulmonary inflammation, less inflammatory cell infiltration and better remodeled airway epithelia in T1-8 group and rDer p1/rDer p2 group than asthma group. However, the airway epithelium structure T1-8 group and rDer p1/rDer p2 group remained similar to that of PBS group. In Conclusion, The recombinant protein T1-8, has effectively alleviated the allergic inflammation of airways and lungs in the experimental mice, suggesting that this synthetic peptide may be used as candidate vaccines for asthma on allergen-specific immunotherapy basis. PMID- 26884957 TI - The clinical performance evaluation of novel protein chips for eleven biomarkers detection and the diagnostic model study. AB - We aimed to develop and validate two novel protein chips, which are based on microarray chemiluminescence immunoassay and can simultaneously detected 11 biomarkers, and then to evaluate their clinical diagnostic value by comparing with the traditional methods. Protein chips were evaluated for limit of detection, specificity, common interferences, linearity, precision and accuracy. 11 biomarkers were simultaneously detected by traditional methods and protein chips in 3683 samples, which included 1723 cancer patients, 1798 benign diseases patients and 162 healthy controls. After assay validation, protein chips demonstrated high sensitivity, high specificity, good linearity, low imprecision and were free of common interferences. Compared with the traditional methods, protein chips have good correlation in the detection of all the 13 kinds of biomarkers (r>=0.935, P<0.001). For specific cancer detection, there were no statistically significant differences between the traditional method and novel protein chips, except that male protein chip showed significantly better diagnostic value on NSE detection (P=0.004) but significantly worse value on pro GRP detection (P=0.012), female chip showed significantly better diagnostic value on pro-GRP detection (P=0.005). Furthermore, both male and female multivariate diagnostic models had significantly better diagnostic value than single detection of PGI, PG II, pro-GRP, NSE and CA125 (P<0.05). In addition, male models had significantly better diagnostic value than single CA199 and free-PSA (P<0.05), while female models observed significantly better diagnostic value than single CA724 and beta-HCG (P<0.05). For total disease or cancer detection, the AUC of multivariate logistic regression for the male and female disease detection was 0.981 (95% CI: 0.975-0.987) and 0.836 (95% CI: 0.798-0.874), respectively. While, that for total cancer detection was 0.691 (95% CI: 0.666-0.717) and 0.753 (95% CI: 0.731-0.775), respectively. The new designed protein chips are simple, multiplex and reliable clinical assays and the multi-parameter diagnostic models based on them could significantly improve their clinical performance. PMID- 26884959 TI - IRAK4 deficiency promotes cardiac remodeling induced by pressure overload. AB - BACKGROUND: Interluekin1 receptor-associated kinase-4 (IRAK4) plays an essential role in the innate immune system. The aim of this study was to investigate the role of IRAK4 in cardiac remodeling induced by pressure overload and elucidate the underlying mechanisms. METHODS: In vivo studies were performed using IRAK4 heterozygous knockout (HET) mice and wild type (WT) mice. Models of cardiac remodeling were induced by aortic banding (AB). Cardiac remodeling was evaluated by Echocardiography and histological analysis. RESULTS: IRAK4 was upregulated in hearts of dilated cardiomyopathy (DCM) patients and also pressure overload induced mice hearts. IRAK4 HET mice exhibited exacerbated cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared with that in WT mice. Furthermore, enhanced activation of the MEK-ERK1/2, p38 and NFkappaB pathways was found in IRAK4 HET mice compared to WT mice. CONCLUSION: Our results suggest that IRAK4 may play a crucial role in the development of cardiac remodeling via negative regulation of multiple signaling pathways. PMID- 26884958 TI - Cytokine profiles in peritoneal dialysis effluent predicts the peritoneal solute transport rate in continuous ambulatory peritoneal dialysis patients. AB - Cytokine profiles in peritoneal dialysis effluent (PDE) vary among patients of continuous ambulatory peritoneal dialysis (CAPD), which may indicate the therapeutic efficiency of CAPD. We examined the cytokine profiles of PDE with stable CAPD and analyzed their relation with the peritoneal solute transport rate (PSTR). The peritoneal equilibration test (PET) was performed to evaluate peritoneal solute transport rate (PSTR) by calculating dialysate/plasma creatinine (D/P Cr). Patients were then divided into either low and low-average transport (L/A), or high and high average transport (H/A) groups according PET results. Overnight PDE were collected from 30 CAPD patients and various cytokines and growth factors were detected using the Luminex Flex Map 3D system. The concentrations of interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha in dialysate were 66.4+/-59.8, 221+/-96.1 and 1.79+/-0.34 pg/mL respectively while IL-17A, IL-17F, IL-21, IL-22 or IL-23 could not be detected. Higher IL-6 levels were found in the H/A group as compared with the L/A group (P<0.05); however MCP-1, TNF-alpha, transforming growth factor (TGF)-beta1 and VEGF levels were not significantly different between these two groups (P>0.05). We found that IL-6, MCP-1, vascular endothelial growth factor (VEGF) and TGF-beta1 levels were closely correlated with each other and all significantly associated with D/P Cr. Multivariate analysis showed that D/P Cr was independently correlated with IL-6 and negatively correlated with serum albumin (r=-0.369, P=0.045). In conclusion, our study indicates that systemic analysis of cytokine profiles in PDE reveals the transport characteristics of CAPD patients. Long-term follow-up study should be necessary to further confirm the value of cytokine detection in evaluation of PD therapeutic efficiency. PMID- 26884960 TI - VKORC1 and CD-14 genetic polymorphisms associate with susceptibility to cardiovascular and cerebrovascular diseases. AB - OBJECTIVE: To investigate the associations of VKORC1 rs2359612 and rs9923231 and CD-14 rs2569190 with susceptibility to cardiovascular and cerebrovascular diseases (CCVD). METHODS: A case-control study was conducted with 614 cases of CCVD patients selected at our hospital between January 2011 and June 2012 as case group and 590 healthy individuals participating physical examination during the same period as control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to detect genotypes of VKORC1 and CD-14 genetic polymorphisms. SHEsis software was used to conduct haplotype analysis and logistic regression analysis was used to identify risk factors for CCVD. RESULTS: The genotype and allele frequencies of VKORC1 rs2359612 and rs9923231 and CD-14 rs2569190 between the case and control groups were statistically different (all P<0.05). Haplotype analysis showed that the frequencies of CAT and TAT haplotypes were significantly higher while the frequencies of TAC and TGC haplotypes were significantly lower in the case group than those in the control group (P = 0.013, 0.029, 0.019 and 0.042, respectively). Logistic regression analysis showed that age, systolic pressure, smoking history and VKORC1 rs2359612 maybe risk factors for CCVD; and body mass index (BMI), diastolic pressure and VKORC1 rs9923231 may be protective factors for CCVD (all P<0.05). CONCLUSION: VKORC1 rs2359612 and rs9923231, and CD-14 rs2569190 might associate with susceptibility to CCVD. CAT and TAT haplotypes may be risk factors while TAC and TGC haplotype may be protective factors for CCVD. PMID- 26884961 TI - Prostaglandin-endoperoxide synthase 2 (PTGS2) rs20417 polymorphism and prostate cancer risk: a meta analysis. AB - BACKGROUND: Genetic variation of SNPs in the PTGS2 gene is reported to be capable of creating tissue milieu favoring tumorigenesis. Some studies have implicated the common SNP rs20417 has association with PCa risk, while others showed reverse results. The study was performed with an aim to reconcile the existing controversy by performing a meta-analysis. METHODS: We searched databases of Embase and PubMed and identified 8 publications fulfilling the specified inclusion criteria. X(2)-based Q-test and I(2) statistic were quantified to measure the heterogeneity across studies. The pooled ORs and 95% CIs were calculated to estimate the association between SNP rs20417 and PCa risk. RESULTS: Based on an enlarged sample size by combining the data from published meta analyses and those missed in them, the results of the present meta-analysis revealed the association of SNP rs20417 and overall PCa risk was not significant. Subgroup analyses according to ethnicity and source of controls did not show any significant results, either. CONCLUSIONS: The meta-analysis suggests that the presence of SNP rs20417 is unlikely to be associated with PCa risk. Our understanding of the genetic risk for PCa should be further expanded and refined through future research in a much larger number of participants. PMID- 26884962 TI - Zinc mediated hepatic stellate cell collagen synthesis reduction through TGF-beta signaling pathway inhibition. AB - This study is to investigate the effect and underlying mechanism of Zinc (Zn) on hepatic stellate cell collagen synthesis. The proliferation and collagen synthesis ability of LX-2 cells were detected after adding Zn. The collagen synthesis related proteins of MMP-13 and TIMP1 along with TGF-beta signaling pathway related proteins were detected by Western blot. The role of TGF-beta signaling pathway in collagen synthesis inhibition was identified by TGF-beta RI siRNA silencing. Compared with control group, LX-2 cell proliferation ability was significantly inhibited at all Zn concentrations (50 MUM, 100 MUM and 200 MUM). Zn at 50 MUM did not affect the protein content of alphaSMA and type I collagen while 100 MUM and 200 MUM Zn could significantly inhibit alphaSMA expression. Compared with control group, gene expression and protein content of MMP-13 in 200 MUM Zn group was significantly increased while no difference in gene expression and protein content of TIMP1 was found. TGF-beta RI content in 200 MUM Zn group was significantly decreased and the protein content of TGF-beta RII was not affected. MMP-13 expression was significantly increased after TGF-beta RI siRNA silencing. Further results showed that in LX-2 cells those TGF-beta RI expression was inhibited, LX-2 cell proliferation ability and the expression of synthesis collagen related proteins of alphaSMA and type I collagen were greatly decreased. Zn could significantly inhibit the expression of alphaSMA and type I collagen by inhibiting TGF-beta RI expression and promoting MMP-13 expression. PMID- 26884963 TI - Increased activation of toll-like receptors-7 and -8 of peripheral blood mononuclear cells and upregulated serum cytokines in patients with pediatric systemic lupus erythematosus. AB - Autoimmune disease systemic lupus erythematosus (SLE) is associated with increased expression of pro-inflammatory cytokines such as interferons (IFNs) and specific interleukins (ILs), which are induced by toll-like receptors (TLRs). The present study aimed to examine the serum levels of cytokines, the activation of TLR-7 and TLR-8 of peripheral blood mononuclear cells (PBMCs) from pediatric SLE patients, and to investigate the response of those PBMCs to viral RNA via the TLR 7 and TLR-8 signaling. Results demonstrated that pediatric SLE patients had increased serum concentrations of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and IFN-alpha, and promoted activation of TLR-7 and TLR-8, compared to control subjects. Moreover, the peripheral blood mononuclear cells (PBMCs) from pediatric SLE patients were more sensitive to the stimulation by the transfection with viral RNA from influenza virus, with a promoted activation of TLR-7 and TLR-8 signaling. In conclusion, pro-inflammatory cytokines, such as IL-1beta, IL-6, IL 8, IL-10, and IFN-alpha were promoted in pediatric SLE patients, with an increased activation of TLR-7 and TLR-8 to the stimuli, such as virus infection. It implies the TLR-7 and TLR-8 activation by virus infection might play an important role in the pathogenesis of pediatric SLE. PMID- 26884964 TI - Lower expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) association with poor prognosis of gastric cancer. AB - BACKGROUND: The aim of this study was to investigate the expression of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) in gastric cancer (GC), and its potential influence on the prognosis of GC patients. METHODS: At present study, we examined the immunohistochemical expression of PHLPP1 on tissue microarrays (TMAs) containing 135 gastric adenocarcinoma tissues and 135 matched adjacent non-tumor tissues. In addition, both semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis (WB) were adopted to detect of the expression of PHLPP1 in the GC cell lines (AGS, SUN-1, KATO-III, BGC-823, MGC-803, SGC-7901, and HGC-27) and the normal gastric cell line GES-1. Survival analysis was used to investigate the efficiency of the prognostic evaluation of PHLPP1 expression in GC patients. RESULTS: Positive expression rate of PHLPP1 in the primary GC tissues was significantly lower than that in adjacent non-tumor tissues (55.6% vs. 87.4%, P<0.001). Both gene transcription (mRNA) and Protein expression of PHLPP1 in the GC cell lines were significantly lower than those in the GES-1 cell line, respectively. The Kaplan-Meier analysis showed that patients presented PHLPP1 negative expression in the GC tissues had significantly lower overall survival rate than those presented PHLPP1 positive expression in the GC tissues (P=0.008). With the multivariate survival analysis (Cox regression), PHLPP1 expression in the GC tissue was identified as an independent predictor of the survival of patients. CONCLUSIONS: This study indicated that aberrant PHLPP1 expression was observed in GC tissues, which was significantly associated with the poor prognostic outcomes of GC patients. PMID- 26884965 TI - Association of susceptibility to septic shock with platelet endothelial cell adhesion molecule-1 gene Leu125Val polymorphism and serum sPECAM-1 levels in sepsis patients. AB - Sepsis is a systemic inflammatory response to infection and includes severe sepsis, septic shock and death. Platelet endothelial cell adhesion molecule-1 (PECAM-1) is one cell adhesion molecule expressed on platelets and leukocytes. It regulates platelet activation and mediates transendothelial migration of leukocytes, thus maintaining the integrity of the vasculature. There are some animal experiments associated with the protective role of PECAM-1 against septic shock. However few host genetic risk factors have been identified for sepsis severity and susceptibility to septic shock. A case-control study was conducted, which included 217 patients with sepsis and 90 control subjects recruited from our hospital. One single nucleotide polymorphisms (SNP) of PECAM-1 gene Leu125Val (C373G) was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum soluble PECAM-1 (sPECAM-1) levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the CG and GG genotypes of SNP in Leu125Val of PECAM-1 (rs668: C>G) was significantly associated with increased susceptibility to septic shock compared with CC genotype in sepsis patients (CG genotype, OR: 2.493, 95% CI: 1.175~5.287, P = 0.016; GG genotype: OR: 3.328, 95% CI: 1.445~7.666, P = 0.004). The serum levels of sPECAM-1 in the sepsis patients (47.1 +/- 17.5 ng/ml) were significantly higher than those in the healthy controls (61.3 +/- 20.9 ng/ml, P<0.01). Among sepsis patients, the serum levels of sPECAM-1 were significantly higher in CG and GG genotype than in CC genotype. In septic shock patients, nonsurvivors (83.7 +/- 12.6 ng/ml, n = 69) had a significantly higher serum sPECAM-1 level than the survivors (76.9 +/- 12.7 ng/ml, n = 53) (P<0.01). In conclusion, PECAM-1 Leu125Val polymorphism and its sPECAM-1 levels are associated with sepsis severity and susceptibility to septic shock. PMID- 26884966 TI - Examining the association of circulating 25-hydroxyvitamin D with kidney cancer risk: a meta-analysis. AB - OBJECTIVE: To examine the relationship between circulating 25-hydroxy-vitamin D (25 (OH) D) and risk of kidney cancer. METHODS: We searched PubMed, EMBASE, and Web of Science databases through August 31, 2015 for eligible studies. Pooled ORs with 95% confidence interval were calculated using fixed effect models. All data analyses were performed with STATA version 12.0. RESULTS: The final analysis included 2 prospective cohort studies and 7 nested case-control studies, with a total of 130, 609 participants and 1, 815 cases of kidney cancer. No obvious heterogeneity was observed between individual studies. The results of this study revealed that higher circulating 25-hydroxyvitamin D levels were associated with lower risk of kidney cancer (OR=0.79, 95% CI 0.69-0.91; P value for heterogeneity: 0.61, I(2)=0%). After stratified by geographical region, the similar association was detected in European studies (OR=0.81, 95% CI 0.69-0.94; P value for heterogeneity: 0.38, I(2)=0%), though no significant association was observed in the USA studies (OR=0.73, 95% CI 0.51-1.04; P value for heterogeneity: 0.44, I(2)=0%). CONCLUSION: Our present findings suggest that higher levels of circulating 25-hydroxyvitamin D could reduce the risk of kidney cancer by 21%. Further well-designed large-scaled prospective studies and randomized controlled trials are warranted to provide more conclusive evidence. PMID- 26884967 TI - Low doses of single or combined agrichemicals induces alpha-synuclein aggregation in nigrostriatal system of mice through inhibition of proteasomal and autophagic pathways. AB - Alpha synuclein (SNCA) genes and environmental factors are important risk factors of Parkinson's disease (PD). The agrichemicals paraquat, maneb and chlorpyrifos selectively target dopaminergic neurons, leading to parkinsonism, through ill defined mechanisms. We analyzed the ability of low dose paraquat, maneb and chlorpyrifos, separately or combined together, to induce synucleinopathy in wild type mice. Paraquat and maneb applied together did not increase alpha-Synuclein (alpha-Syn) levels. By contrast, paraquat and chlorpyrifos together resulted in robust accumulation of alpha-Syn in striata in mice. Therefore, co-treatment with chlorpyrifos enhanced the effects of paraquat. Paraquat, and its co-treatment with maneb or chlorpyrifos, inhibited all soluble proteasomal expression of 26S proteasome subunits. Both paraquat and chlorpyrifos treatments increased levels of the autophagy inhibitor, mammalian target of rapamycin, mTOR, suggesting impaired axonal autophagy, despite increases in certain autophagic proteins, such as beclin 1 and Atg 12. Autophagic flux was also impaired, as ratios of LC3 II to LC3 I were reduced in all the treated animals. These results suggest that a combination of paraquat and chlorpyrifos is much more toxic than paraquat alone or combined with maneb. These effects are likely via inhibitory effects of these toxins on proteasomes and autophagy, which lead to accumulation of alpha-Syn. Our study provides a novel insight into the mechanisms of action of these agrichemicals. PMID- 26884968 TI - In vitro effects of mitomycin C on the proliferation of the non-small-cell lung cancer line A549. AB - Non-small-cell lung cancer (NSCLC) is the leading cause of death from cancer in the United States. Chemotherapy prolongs survival among patients with advanced disease, but at the cost of clinically significant adverse effects. As a novel promising oncotherapy method, induced differentiation by mitomycin C has been applied for NSCLC therapy at recent year. In this study, the molecular mechanism of differentiation interruption by mitomycin C in the NSCLC line A549 was investigated. High dosage of mitomycin C (300 uM) could significantly inhibit cell proliferation (P < 0.05) by 48.39 +/- 3.32% (P < 0.05), under which cell shrinkage and disruption were observed. Flow cytometry assay showed that the proportion of G1/G0 cells significantly increased, while that of S and G2/M cells significantly decreased after treatment of mitomycin C (10 or 300 uM) for 24 h. These results indicated that cell arrest by mitomycin C appeared. Additionally, up-regulation of retinoblastoma (Rb) gene by low concentration of mitomycin C (10 uM) was detected using immunohistochemistry (IHC) and Western blot assay, indicating a role in the regulation of cell cycle inhibition of this cell line. PMID- 26884969 TI - Intracranial aspergillus fumigatus infection complicated with cavernous hemangioma: case report and literature review. AB - The aim of this study was to report a rare case of Aspergillus fumigatus infection complicated with cavernous hemangioma in the central nervous system of a patient with normal immune function and to investigate its causes. A 60-year old male patient was admitted three years ago due to meningioma-induced convulsions. In addition to meningioma, magnetic resonance imaging (MRI) results also suggested the presence of cystic and solid lesions in the left temporal lobe, which was considered to be a brain abscess due to the infection. After antibiotic treatment, the patient underwent meningioma resection, after which no more convulsions occurred. It was recommended that the patient receive treatment on the abscess in the left temporal lobe, but the patient did not consent. He was discharged with follow-up. Recently, the patient returned for treatment due to intermittent headaches with weakness in the right lower extremity for 10 days. MRI results revealed that the lesion in the left temporal lobe had expanded and was associated with abnormality in the midline. Surgical lumpectomy was performed, and the postoperative pathological examination confirmed the brain abscess to be an Aspergillus fumigatus infection complicated with cavernous hemangioma, which indirectly confirmed that the lesion in the temporal lobe three years ago was from the Aspergillus fumigatus infection. On the 7th postoperative day, the patient died due to severe pneumonia. Because the intracranial Aspergillus fumigatus infection in the patient had lasted for three years, with no cavernous hemangioma present at the first assessment but with a lesion evident three years later, the hemangioma is considered to be related to the Aspergillus fumigatus infection. PMID- 26884970 TI - Baicalin inhibits PDGF-induced proliferation and migration of airway smooth muscle cells. AB - Airway smooth muscle (ASM) cell proliferation and migration play important roles in airway remodeling in asthma. In vitro platelet-derived growth factor (PDGF) induced ASM cell proliferation and migration. Baicalin is one of flavonoid extracts from Scutellaria baicalensis, which has an anti-asthma effect. However, little is known about its role in PDGF-induced proliferation and migration in rat ASM (RASM) cells. In this study, we aimed to investigate the effects of baicalin on PDGF-induced RASM cell proliferation and migration. We also identified the signaling pathway by which baicalin influences RASM cell proliferation and migration. In the current study, we demonstrated that baicalin suppressed PDGF induced RASM cell proliferation, arrested PDGF-induced cell-cycle progression. It also suppressed PDGF-induced RASM cell migration. Furthermore, baicalin suppressed PDGF-induced expression of phosphorylated p38, ERK1/2 and JNK in RASM cells. In summary, our study is the first to show that baicalin pretreatment can significantly inhibit PDGF-induced RASM cell proliferation and migration by suppressing the MAPK signaling pathway, and baicalin may be a useful chemotherapeutic agent for asthma. PMID- 26884971 TI - The association between elevated cystatin C levels with myocardial infarction: a meta-analysis. AB - OBJECTIVE: Cystatin C is a well established marker of kidney function. There is evidence that cystatin C concentrations are also associated with myocardial infarction. The purpose of the present study is to clarify the link between cystatin C with myocardial infarction using a meta-analysis approach. METHODS: We searched articles indexed in the Pubmed and Sciencedirect published as of August 2015 that met our predefined criteria. A meta-analysis was used to pool estimates of the multivariate adjusted relative risk (RR) with 95% confidence interval (CI), of the association between cystatin C and subsequent risk of myocardial infarction. RESULTS: Four eligible articles with 10491 subjects from 5 cohort studies were considered in the analysis. Overall, the random-effects meta analysis results indicated that the highest cystatin C category versus lowest was associated with greater risk of myocardial infarction (RR, 1.78; 95% CI, 1.27 to 2.49; P=0.001). No evidence of publication bias was observed. CONCLUSIONS: This meta-analysis showed that cystatin C is strongly and independently associated with subsequent risk of myocardial infarction. Further investigation is warranted to clarify whether measurement of cystatin C can usefully reduce the myocardial infarction beyond established predictors already in clinical use. PMID- 26884972 TI - DYNA CT arteriographic evaluation of hepatocellular carcinoma for treatment by trans-catheter arterial chemoembolization. AB - PURPOSE: The aim of our study was to determine whether using C-arm CT (DYNA CT) during hepatic arteriography imaging assists in TACE treatment. MATERIALS AND METHODS: 138 patients with HCC, 69 patients (Group A) underwent DYNA CT and routine digital subtraction angiography (DSA), while another 69 patients (Group B) underwent only DSA, were prospectively studied at a single facility between May 2011 and September 2012. Liver vessels and tumors were displayed by DYNA CT. The superior mesenteric artery (SMA) and the celiac artery shape and branch anatomy were visualized. The number of tumors and arteries which feed these was compared. RESULTS: In Group A, DYNA CT showed that the hepatic artery originated from the celiac artery in 60 patients, while the right hepatic artery originated from the SMA and the left hepatic artery originated from the common hepatic artery in 9 patients. In 10 patients, the phrenic artery provided blood to the tumor. DYNA CT detected 258 lesions, while routine DSA found 178 lesions (P<0.05). CONCLUSION: DYNA CT has substantial advantages over routine DSA in demonstrating the shape and branches of the target hepatic vessels and the number of tumors. DYNA CT provides important guidance for TACE which simplifies selective catheterization and improves the treatment and quality of TACE. PMID- 26884973 TI - Association between human cytomegalovirus and onset of epilepsy. AB - OBJECTIVE: To explore the association between human cytomegalovirus (HCMV) and epilepsy. METHODS: Epilepsy patients (n = 112) in neurology clinic of our hospital during January 2012 and December 2014 were allocated to the case groups, including intractable epilepsy group (n = 96) and non-intractable epilepsy group (n = 16). Healthy individual (n = 120) who received physical examination during the same period were allocated to the control group. The expression of serum HCMV late gene pp67-RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of serum HCMV immunoglobulin G (IgG), immunoglobulin M (IgM) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA). Serum hypersensitive c-reactive protein (hs-CRP) was detected by latex-enhanced immunoturbidimetry. The electroencephalogram (EEG) of refractory epilepsy group, non-refractory epilepsy group and control group were recorded. RESULTS: The expression of pp67-mRNA was significantly higher in intractable epilepsy group than non-intractable epilepsy group (P < 0.05) and control group (P < 0.001). The HCMV-IgG positive rate and HCMV-IgM positive rate were significantly higher in intractable epilepsy group than control group (both P < 0.001). The HCMV-IgM positive rate was significantly higher in intractable epilepsy group than non-intractable epilepsy group (P < 0.001). The HCMV-IgM positive rate was significantly higher in non-intractable epilepsy group than control group (P < 0.001). The hs-CRP and IL-6 levels presented descending trends respectively in intractable epilepsy group, non-intractable epilepsy group and control group (all P < 0.001). CONCLUSION: HCMV was prominently expressed in epilepsy and might contribute to the development of epilepsy. PMID- 26884974 TI - Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways. AB - Ovarian cancer is the most lethal gynecologic malignancy. Cisplatin is a very effective cancer chemotherapy drug, but cisplatin resistance is a crucial problem of therapy failure. Overexpression of PVT1 has been demonstrated in ovarian cancer. The mRNA level of PVT1 in ovarian cancer tissues of cisplatin-resistant patients and cisplatin-sensitive patients, cisplatin-resistant cells SKOV-3/DDP and A2780/DDP, cisplatin-sensitive cells SKOV-3 and A2780 were determined by qRT PCR. The influence of the knockdown or overexpression of PVT1 on cisplatin resistance was measured by measuring the cytotoxicity of cisplatin and the apoptotic rate of ovarian cancer cells was detected by CCK-8 assay and flow cytometry, respectively. The mRNA levels and protein expression of TGF-beta1, Smad4, p-Smad4 and Caspase-3 in apoptotic pathways were determined. The mRNA level of PVT1 was significantly higher in ovarian cancer tissues of cisplatin resistant patients and cisplatin-resistant cells. SKOV-3/DDP and A2780/DDP cell viability and the percentage of apoptotic cells after transfection with PVT-1 siRNA and treated with cisplatin was markedly lower and higher than the control, respectively. Moreover, the overexpression of PVT1 exhibited the anti-apoptotic property in SKOV-3 and A2780 cells after transfection with LV-PVT1-GFP and treated with cisplatin. The mRNA levels and protein expression of TGF-beta1, p Smad4 and Caspase-3 were much higher in cisplatin-resistant cells transfected with siPVT1. Overexpression of LncRNA PVT1 in ovarian cancer promotes cisplatin resistance by regulating apoptotic pathways. PMID- 26884975 TI - Allicin inhibits human renal clear cell carcinoma progression via suppressing HIF pathway. AB - Hypoxia-inducible factor 1-alpha (HIF-1alpha) protects hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions. Allicin is characterized by the anti-cancer characteristics. This study aims to explore whether allicin is involved in renal clear cell carcinoma progression through HIF 1alpha. A total of 40 RCC tissues and 39 normal renal tissues were collected H&E and immunohistochemistry were applied to study morphology changes. MTT assay and flow cytometry (FCM) were used to analyze cell viability and apoptosis. In vitro colony formation assay and wound healing assay were conducted to explore cell migration. The protein levels of Bcl-2, VEGF and HIF-1alpha were increased in RCC tissues. More importantly, treatment with allicin significantly decreased HIF 1alpha protein level, thereby reducing Bcl-2 and VEGF expression. In addition, allicin also obviously enhanced apoptotic cells. And colony formation capacity and cell migration rate were reduced in RCC-9863 cells treated with allicin. Further study revealed that overexpression of HIF-1alpha could partially repress allicin-induced downstream effects. To conclude, allicin inhibits human renal clear cell carcinoma progression partially by suppressing HIF pathway. PMID- 26884976 TI - Efficacy of hepatic resection for huge (>= 10 cm) hepatocellular carcinoma: good prognosis associated with the uninodular subtype. AB - BACKGROUND: The value of hepatic resection (HR) for huge hepatocellular carcinomas (HCC) (>= 10 cm in diameter) remains controversial. The aim of this study is to evaluate the efficacy of hepatic resection (HR) for patients with huge HCC. METHODS: A total of 739 patients with huge HCC (>= 10 cm in diameter) (huge HCC group, n = 244) or small HCC (< 10 cm in diameter) (small HCC group, n = 495) who received initial HR were retrospectively analyzed. Overall survival (OS) and disease-free survival (DFS) were obtained using the Kaplan-Meier method and compared by Log-Rank test. Prognostic factors of huge HCC were identified based on Cox regression analyses. RESULTS: The hospital mortality of these two groups were similar (P = 0.252). The 5-year OS of huge HCC group and small HCC group were 30.3% and 51.9%, respectively (P < 0.001). Uninodular huge HCC had a significant higher 5-year OS (50.6%) than mutinodular huge HCC (26.9%) (P = 0.016). Multivariate analysis revealed that uninodular huge HCC and absence of PVTT independently predicted better OS for huge HCC patients. CONCLUSION: HR is a safe and effective approach for the treatment of huge HCC, especially for the uninodular subtype. PMID- 26884977 TI - Meta-analysis of the effect of postoperative radiotherapy on prognosis of prostatic cancer following radical prostatectomy. AB - OBJECTIVE: A systematic evaluation was carried out over the effectiveness and safety of postoperative radiotherapy following radical prostatectomy. METHOD: The randomized controlled trials that were concerned with postoperative radiotherapy for prostatic cancer and published before June 2014 were searched in PubMed, EMBASE, Cochrane Library, CBM, CNKI and VIP databases. Two researchers conducted quality evaluation and data extraction independently for all included literature. Rev Man 5.2 software was used for statistical analysis. RESULTS: Finally 5 randomized control trials involving 2290 cases were included. Meta-analysis showed that the approaches of radical prostatectomy with or without postoperative radiotherapy did not differ significantly in terms of overall survival (HR=1.09, 95% C1: 0.75-1.60, P=0.65). However, significant difference was found in biochemical progression-free survival (HR=0.54, 95% CI: 0.42-0.69, P < 0.001). CONCLUSION: Evidences show that postoperative radiotherapy following radical prostatectomy can increase biochemical progression-free survival but not overall survival. PMID- 26884978 TI - IGF-I CA19 repeat polymorphisms and cancer risk: a meta-analysis. AB - IGF-I CA repeat polymorphisms, especially the allele containing CA19 repeats, have been reported to be associated with the risk for various types of cancers. However, the results still remain controversial and ambiguous. This meta-analysis was performed to evaluate the association between IGF-I CA19 repeat polymorphisms and the risk of cancer. Total 18 studies with IGF-I CA19 repeat genotyping on 9,873 patients and 15,607 controls were analyzed. We used random-effects model with a pooled OR of 0.69 (95% CI = 0.60-0.79) for the recessive genetic model, 0.97 (95% CI = 0.86-1.10) for the dominant genetic model, 0.99 (95% CI = 0.86 1.14) for the homozygote comparison and 1.06 (95% CI = 0.91-1.23) for the heterozygote comparison. In the subgroup analysis of recessive model, OR (95% CI) was 0.65 (0.52-0.80) in breast cancer, 0.68 (0.53-0.86) in prostate cancer, and 0.71 (0.52-0.96) in Caucasian. In conclusion, IGF-1 CA19 repeat polymorphisms are unlikely to be a major determinant of susceptibility to cancer. However, the subgroup analysis of recessive model indicates that IGF-I CA19 repeat polymorphisms may reduce the risk of certain types of cancer or in a specific population. PMID- 26884979 TI - Reduced metallothionein expression induced by Zinc deficiency results in apoptosis in hepatic stellate cell line LX-2. AB - The present study is to investigate the molecular mechanism by which Zinc (Zn) deficiency induces apoptosis in hepatic stellate cells. LX-2 cells were incubated with N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN; 5 MUM, 10 MUM and 25 MUM) for 24 h. MTT assay was used to test the proliferation ability of LX 2 cells. Flow cytometry was performed to detect cell apoptosis. Western blotting assay was employed to determine the expression of metallothionein (MT). Atomic absorption spectroscopy was performed to measure intracellular reactive oxygen species content. To test the activity of mitochondria, respiratory control rate was tested. To investigate the activation of apoptotic signaling pathway, cytochrome C oxidase activity was determined. TPEN effectively decreased the content of Zn in LX-2 cells. Zn deficiency led to the inhibition of proliferation and enhancement of apoptosis of LX-2 cells. Zn deficiency induced the inhibition of MT expression in LX-2 cells. Inhibition of MT expression induced by Zn deficiency resulted in enhanced reactive oxygen species content, impaired mitochondrial function and inhibition of cytochrome C oxidase activity. Intracellular MT content in LX-2 cells is reduced by Zn deficiency. Reduction in MT expression further increases intracellular ROS content, enhances oxidative stress, inhibits cytochrome C oxidase activity, impairs mitochondrial function, and finally leads to cell apoptosis. PMID- 26884980 TI - MicroRNA profiling identifies miR-129-5p as a regulator of EMT in tubular epithelial cells. AB - The importance of microRNAs in various diseases has been demonstrated, but their potential role in the pathogenesis of renal fibrosis needs to further research. We have profiled changes in microRNA levels in human kidney proximal tubular cell line HK-2 with TGF-beta treatment and identified significantly altered miRNAs. miR-129-5p, was one of the significant down-regulated miRNAs in experimental models. PDPK1 was a potential target gene of miR-129-5p and luciferase assay analysis identified PDPK1 as a new direct target gene of miR-129-5p. Further research indicated that miR-129-5p suppressed PDPK1 mRNA and protein levels in HK 2 cells. miR-129-5p inhibited EMT via PDPK1 in HK-2 cells. In a conclusion, our findings suggested that miR-129-5p may function as a suppressor in renal fibrosis by targeting PDPK1. PMID- 26884981 TI - Role of microRNA-134 in the neuroprotective effects of propofol against oxygen glucose deprivation and related mechanisms. AB - This study is to investigate the effects of propofol on primary hippocampal neurons under oxygen-glucose deprivation (OGD) condition and related mechanisms. The apoptotic process was detected with flow cytometry, and the cell viability was assessed with CCK-8 assay. The expression levels of microRNA (miRNA)-134 were detected with quantitative real-time PCR. Protein expression levels were detected by Western blot analysis. Dual-luciferase reporter assay was also performed to confirm the prediction of the target genes of miRNA-134. Our results from flow cytometry showed that the apoptosis rate was significantly increased in the primary hippocampal neurons under OGD condition. However, the treatments of propofol (25, 50, 100, and 150 umol/L) suppressed the apoptotic process. Moreover, propofol restored the declined cell viability in the primary hippocampal neurons under OGD condition. In addition, compared with the OGD model group, the Bcl-2/Bax ratios were significantly elevated in the propofol-treated groups, indicating the protective effects of propofol against cellular apoptosis. Quantitative real-time PCR showed that propofol reduced the expression levels of miRNA-134 in the primary hippocampal neurons under OGD condition. Bioinformatics analysis revealed that BDNF might be a target of miRNA-134. The treatment of antago-miRNA-134 significantly down-regulated the expression level of BDNF. In line with this, dual-luciferase reporter assay suggested that miRNA-134 targeted BDNF in the 3'-TUR. Under OGD condition, propofol could down-regulate miRNA-134, and subsequently modulate the expression of BDNF, to exert neuroprotective effects. PMID- 26884982 TI - Role of ornithine decarboxylase/polyamine pathway in focal cerebral ischemia reperfusion injury and its mechanism in rats. AB - OBJECTIVE: To observe the role of ornithine decarboxylase (ODC)/polyamine pathway in focal cerebral ischemia-reperfusion injury and to explore its mechanism in rats. METHODS: This study was randomly divided into 3 groups including sham operation (sham) group, ischemia-reperfusion (I/R) group and alpha difluoromethylornithine (DFMO) group (each group with 80 rats). In DFMO group, 300 mg/kg of DFMO was injected by tail vein 24 h before reperfusion. According to different time points (3 h, 12 h, 24 h, 48 h and 72 h) after reperfusion, each group was divided into 5 subgroups (each subgroup with 16 rats). RESULTS: In I/R group, apoptosis began increasing 3 h after reperfusion, reached a peak 24 h after perfusion and began decreasing 48 h after perfusion. Compared with sham group, apoptosis significantly increased in I/R and DFMO groups (P<0.05). However, apoptosis was significantly lower in DFMO group than in I/R group at each time point (P<0.05). In I/R group, CHOP expression began increasing 3 h after reperfusion, reached a peak 24 h after perfusion and began decreasing 48 h after perfusion. CHOP expression was significantly lower in DFMO group than in I/R group at each time point (P<0.05). The level of polyamines was significantly higher in I/R and DFMO groups than in sham group, and in I/R group than in DFMO group 12 h, 24 h and 48 h, respectively (P<0.05). CONCLUSION: Down-regulation of ODC/polyamine pathway may inhibit CHOP-mediated apoptosis caused by endoplasmic reticulum stress and plays a protective role in cerebral I/R injury. PMID- 26884983 TI - Immuno-enhancement effects of Lycium ruthenicum Murr. polysaccharide on cyclophosphamide-induced immunosuppression in mice. AB - Lycium ruthenicum Murr. is commonly used in traditional Tibetan medicine, and the fruits of Lycium ruthenicum Murr. contain an immunologically active pectin which improves immune function against chronic diseases. The present study was performed to evaluate the immunomodulatory effects of Lycium ruthenicum Murr. polysaccharide 3 (LRGP3) in cyclophosphamide (Cy)-induced immunosuppressed mice. Mice were injected intraperitoneally once daily with low-dose (25 mg/kg), intermediate-dose (50 mg/kg), high-dose (100 mg/kg) of LRGP3 for 10 consecutive days, respectively. Compared with Cy group, LRGP3 accelerated recovery of spleen and thymus indices, enhanced T cell and B cell proliferation responses, as well as peritoneal macrophage phagocytosis. In addition, LRGP3 treatment restored the levels of interleukin-2 (IL-2), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in the serum of Cy-treated mice. These results indicate that LRGP3 plays an important role in the protection against immunosuppression in Cy-treated mice and could be a potential immunomodulatory agent. PMID- 26884984 TI - Effects of glucose administered with lidocaine solution on spinal neurotoxicity in rats. AB - To investigate whether intrathecal administration of 10% glucose increases functional impairment and histologic damage in rats when mixed with 5% lidocaine. After implanted intrathecal catheter, 32 male Sprague-Dawley rats were randomly assigned to one of four groups: lidocaine group (Group L, n=8) received 5% lidocaine 20 uL, lidocaine with glucose group (Group LG, n=8) received 5% lidocaine with 10% glucose 20 uL, glucose group (Group G, n=8) received 10% glucose 20 uL and normal saline group received normal saline 20 uL (Group NS, n=8). Four days after intrathecal injection, sensory impairments of rats in the four groups were evaluated by using the tail-flick test. The histologic changes of spinal cord and nerve roots were observed by electron microscopy and light microscopy. There was no significant difference in baseline tail-flick latencies between the four groups (P=0.284). On the 4th day after intrathecal injection, the assessment result of sensory function was similar to baseline (P=0.217) in saline-treated animals. Sensory impairment occurred after intrathecal administration of 5% lidocaine, and 10% glucose with 5% lidocaine worsen this satiation (P=0.0001); histologic changes in 10% glucose with 5% lidocaine-treated group has differ significantly from lidocaine-treated group (P=0.001). Sensory function after intrathecal administration of 10% glucose was similar to baseline and did not differ from the saline group (P=0.995); histologic changes in 10% glucose-treated rats did not differ significantly from saline controls (P=0.535). These results suggest that 5% lidocaine can induce spinal neurotoxicity and 10% glucose with 5% lidocaine could worsen spinal neurotoxicity. PMID- 26884985 TI - Inhibition of phosphoinositide 3-kinase delta attenuates experimental autoimmune encephalomyelitis in mice. AB - The phosphoinositide 3-kinase delta (PI3Kdelta) has been implicated in multiple signaling pathways involved in autoimmune diseases. We here aimed to test the hypothesis that selective inhibition of PI3Kdelta may promote anti-inflammatory effects by inhibiting Th1 and Th17 cells. We investigated the therapeutic efficacy of a selective PI3Kdelta inhibitor IC87114 in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The efficacy was evaluated based on clinical scores, histopathology, serum cytokines and inflammatory infiltrations in the central nervous system (CNS). Treatment of EAE mice with IC87114 reduced the clinical symptoms, histopathology and cellular infiltration into the CNS. And treatment of EAE with IC87114 suppressed the Th1 and Th17 cell ratios. Consistently, the serum levels of IL-1beta, IL-6, IL-17 and INF-gamma were markedly reduced by IC87114. Taken together, our studies demonstrate that inhibition of PI3Kdelta may serve as novel therapy to suppress neuroinflammation seen during EAE. PMID- 26884986 TI - Analysis on the sequence of the whole genome of an isolated enterovirus 71 strain. AB - An enterovirus 71 (EV71) strain Query was isolated from a patient specimen in 2015. In order to known about its genetic evolution, this study amplified gene fragment of the isolated stain by RT-PCT and carried out sequencing of the total genome. The homology and genetic evolution of the gene sequence of the virus strain in the study were analyzed. The results showed that the isolated EV71 strain in this study had higher homology of nucleotide sequence and amino acid sequence with other virus strains, which was 80%-97% and 88% to 92%, respectively, but it had lower homology with Cox.A16 (homology of nucleotide sequence and amino acid sequence of Cox.A16 was 81% and 79%, respectively). Compare of homologous sequence at the encoding region VP1 demonstrated that the experimental isolated strain EV71 had higher homology of amino acid sequence at VP1 region with other virus strains. Genetic evolution of nucleotide sequence at VP1 region of the identified strain and other EV71 strains was analyzed, and the results demonstrated gene sequence at VP1 region and 5'UTR region of the isolated strain and SDLY017 strain was at the same branch, both of which belonged to C4a, a subtype of type C4. PMID- 26884987 TI - beta-asarone prevents Abeta25-35-induced inflammatory responses and autophagy in SH-SY5Y cells: down expression Beclin-1, LC3B and up expression Bcl-2. AB - Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Inflammatory responses and autophagy have been implicated in the amyloid-beta (Abeta) aggregation in Alzheimer's disease. Although major evidence indicates that macro autophagy is involved in the pathogenesis of AD, its exact role is still unclear. beta-asarone, a major component of Acorus tatarinowii Schott, has various neuroprotective effects. However, little is known about the protection of beta-asarone against inflammation response and autophagy. In the present study, we investigated the neuroprotective effects of beta-asarone on Abeta25-35 induced inflammatory responses and autophagy, and the possible mechanism. Our results showed that beta-asarone attenuated inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 production. Meanwhile, beta-asarone could significantly reduce Beclin-1, LC3B and increase anti-apoptotic protein Bcl-2 level. These results showed that beta asarone protected cells from Abeta25-35 induced inflammation and attenuated autophagy via Bcl-2/Beclin-1 pathway. Our findings suggested that beta-asarone might be a potential preventive drug for AD. PMID- 26884988 TI - Polyphyllin I (PPI) increased the sensitivity of hepatocellular carcinoma HepG2 cells to chemotherapy. AB - In this study the antitumor effects of polyphyllin I (PPI) were investigated in hepatocellular carcinoma HepG2 cells. Our data showed that PPI treatment exerted dose-dependent cytotoxicity on HepG2 cells as previously reported. Furthermore, PPI could sensitize HepG2 cells to cisplastin treatment in concentration dependent manner. The molecular mechanisms of PPI actions involved nuclear factor kappaB (NF-kappaB) and its downstream gene products. PPI treatment dose dependently could decrease the constitutive phosphorylation of NF-kappaB subunit p65 protein and its downstream target genes expression, such as Bcl-2, c-Myc and VEGF. PPI could also inhibit cisplatin-evoked increase of p65 protein phosphorylation and its downstream genes expression, which could be further decreased by combination with NF-kappaB specific inhibitor, PDTC. The cytotoxicity and chemosensitization effects of PPI on HepG2 cells were greatly potentiated by concomitant treatment with PDTC. Taken together, our data confirmed the cytotoxicity of PPI on hepatocellular carcinoma HepG2 cells and provided new findings about PPI sensitizing HepG2 cells to chemotherapy. Moreover, our data also indicated the involvement of NF-kappaB signaling pathway in PPIactions for the first time. PMID- 26884989 TI - Outcome of radiofrequency ablation over partial nephrectomy for small renal mass (<4 cm): a systematic review and meta-analysis. AB - OBJECTIVE: A meta-analysis was undertaken to provide evidence-based clinical trials comparing radiofrequency ablation with partial nephrectomy for small renal mass. METHODS: We searched through the major medical databases such as Pub Med, EMBASE, Medline, Science Citation Index, Web of Science and CNKI (Chinese National Knowledge Infrastructure Database) and Wangfang (Database of Chinese Ministry of Science & Technology) for all published studies without any limit on language from May 2007 until May 2015. The following search terms wereused: partial nephrectomy, radiofrequency ablation, renal cell carcinoma, small renal tumor or mass. Furthermore, additional related studies were manually searched in the reference lists of all published reviews and retrieved articles. RESULTS: We found there were no statistical differences between groups in 5y-DFS, recurrence rates, complications, but a less percentage decease rate of GFR than PN, and RFA may be a better application for SRM (<4 cm). PMID- 26884990 TI - Acute promyelocytic leukemia transformation in a patient with aplastic anemia: a case report with literature review. AB - Aplastic anemia (AA) is a hematological disorder presenting with pancytopenia in peripheral blood and hypocellularity in bone marrow. AA patients with immunosuppressive therapy and granulocyte colony-stimulating factor treatment have a risk of development of acute leukemia including acute myeloid leukemia (M0, M1, M2, M4, M5, M6) and acute lymphoblastic leukemia. However, AA with transformation to acute promyelocytic leukemia (APL) has never been reported. Here, we reported a patient initially diagnosed with AA. while 19 years later, PML/RAR alphafusion gene were detected and the patient was eventually diagnosed as APL. The diagnosis and management of this interesting case are discussed. PMID- 26884992 TI - Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis. AB - This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-alpha) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-alpha gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: 308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-alpha -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-alpha -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-alpha -238G>A, while TNF-alpha -308G>A is in African population. PMID- 26884991 TI - The safety and efficacy of laparoscopic and open hepatectomy in hepatocellular carcinoma patients with liver cirrhosis: a systematic review. AB - BACKGROUND: Compared with open hepatectomy (OH), laparoscopic hepatectomy (LH) had better short-term outcomes in normal hepatocellular carcinoma (HCC) patients. Since liver cirrhosis is the major risk of HCC, serve postoperative complications can be observed after LH in HCC patients with cirrhosis. We conducted this systematic review to analysis the safety and the efficiency of LH in HCC patients with liver cirrhosis. METHODS: MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database, and clinical trial registries were searched through March 2015. Risk ratios (RRs), weigh mean difference (WMD) and 95% confidence intervals (CIs) were calculated. RESULTS: The analysis included 7 retrospective trials, altogether involving 828 patients. Patients in LH group had wider tumor margin (WMD = 0.12, 95% CI 0.04 to 0.21, P = 0.003), less blood loss (WMD = -157.25, 95% CI -295.05 to -19.45, P = 0.03), less blood transfusion (RR = 0.41, 95% CI 0.22 to 0.74, P = 0.004), less postoperative mobility (RR = 0.48, 95% CI 0.35 to 0.66, P<0.001) and less hospital stay (WMD = -4.11, 95% CI -6.23 to -1.98, P<0.001). Overall survival (OS) and disease free survival (DFS) were similar between 2 groups, except LH had a better 5-year survival rate (RR = 1.28, 95% CI 1.01 to 1.62, P = 0.04). CONCLUSION: In HCC patients with liver cirrhosis, LH have short-term outcomes advantages of tumor margin, blood loss, blood transfusion, postoperative mobility, and hospital stay. OS and DFS were similar between LH and OH. LH is safe in HCC patients with liver cirrhosis. PMID- 26884993 TI - The relationship between promoter methylation of p16 gene and bladder cancer risk: a meta-analysis. AB - PURPOSE: Many scientific evidences suggested that the methylation of p16INK4a (p16) was associated with bladder cancer, but some existing studies have yielded inconclusive results about the relationship between p16 promoter methylation and pathological features or the tumor grade of bladder cancer. This meta-analysis of studies aims to evaluate the clinical and prognostic significance of p16 methylation in bladder carcinogenesis. METHODS: Studies were systemically searched via PubMed and Google Scholar in English up to Sept 2015 and a total of ten appropriate studies (693 cases and 290 controls) with an average NOS score of 6.8 were included. The quality of the appropriate studies was measured by the Newcastle-Ottawa Scale (NOS) assessment. RESULTS: The meta-analysis results revealed that the methylation state of p16 was statistically significantly associated with an increased risk of bladder cancer (OR=6.71, 95% CI=3.79-11.87) compared to control, and there is no statistically significantly association between the p16 methylation and the tumor pTNM staging (OR=0.59, 95% CI=0.22 1.60) or the tumor grade (OR=1.01, 95% CI=0.52-1.94) in p16 methylated patients compared to unmethylated patients. CONCLUSIONS: our meta-analysis indicates that p16 promoter methylation may be a promising biomarker for the diagnosis of bladder cancer and the inactivation of p16 may be an early event in bladder carcinogenesis. More studies with larger numbers of participants worldwide are needed to further identify the obvious association above. PMID- 26884994 TI - Liver dysfunction as an important predicting risk factor in patients undergoing cardiac surgery: a systematic review and meta-analysis. AB - Liver function is not considered as a risk factor by current risk scores, such as EUROSCORE II or STS-Score for cardiac surgery. The aim of this study was to review the role of liver dysfunction, classified by the Child-Turcotte-Pugh classification or model for end-stage liver disease scores, as a risk factor for mortality and morbidity of patients following cardiac surgery. The Pubmed referencing library was searched. The rates of mortality and morbidity were calculated using SPSS software. The mortality rates in patients of Child class A, Child class B, and Child class C were pairwise compared respectively. A total of 22 reports including 939 patients from eight countries were reviewed. The mortality rate of patients increased in accordance with increased CTP classification. The lowest mortality rate was recorded in Child class A patients, followed by Child class B patients and the highest mortality rate was observed in Child class C patients. The mean complication rate ranged from 3.82% to 22.15%. Child class C patients should be considered unacceptable for cardiovascular surgery. As two studies revealed, patients with a higher MELD score had significantly higher mortality rates. Liver function should be viewed as an important risk factor for cardiovascular surgery, based on its strong association with mortality and morbidity. PMID- 26884995 TI - Glutamine synthetase predicts adjuvant TACE response in hepatocellular carcinoma. AB - BACKGROUND: Adjuvant transcatheter arterial chemoembolization (TACE) is associated with better outcome and reduced tumor recurrence in hepatocellular carcinoma (HCC) patients. This study aimed to investigate the relationship between glutamine synthetase (GS) expression and survival of HCC patients after postoperative adjuvant TACE. METHODS: We retrospectively analyzed 554 HCC patients in two independent cohorts who underwent curative resection. Immunohistochemistry assay was used to investigate the expression of GS protein and evaluate the association with survival and the response to adjuvant TACE. RESULTS: In training cohort, patients with low GS expression who received postoperative adjuvant TACE showed a better overall survival (OS) (P<0.001) and less early phase recurrence (P=0.016). Adjuvant TACE was an independent prognostic factor for 5-year OS (HR=0.408, 95% CI 0.261-0.639, P<0.001) and early phase recurrence (HR=0.592, 95% CI 0.376-0.931, P=0.023). The same result was confirmed in validation cohort. Patients with high GS expression in both cohorts did not have a significant response to adjuvant TACE in OS and early phase recurrence. CONCLUSIONS: GS status in tumor might be a useful tool in the selection of HCC patients who would be likely to benefit from postoperative adjuvant TACE. PMID- 26884996 TI - Effects of Wenyangzhenshuai Granule on ERK1/2 and ERK5 activity in the myocardial tissue in a rabbit model of adriamycin-induced chronic heart failure. AB - OBJECTIVE: To elucidate the effects of Wenyangzhenshuai granule on expression of extracellular signal-regulated kinase 1/2 (ERK1/2) and 5 (ERK5) in the myocardial tissue using a rabbit model of adriamycin-induced chronic heart failure. MATERIALS AND METHODS: Rabbits were divided into heart failure positive control, adriamycin injection, and adriamycin injection with Wenyangzhenshuai treatment (low, medium and high dose) groups. Cardiac function and cardiac hypotrophy were measured in all groups. Besides, myocardial expression of ERK1/2 and ERK5 phosphorylation were evaluated by Western blotting and ERK1/2 and ERK5 mRNA levels by RT-PCR. The cardiac structure and cardiac function were also compared using histology staining and electron microscope. RESULTS: Adriamycin injection led to cardiac failure reflected by decreased left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), E/A ratio, and increased cardiac hypertrophy, both of which have been improved by Wenyangzhenshuai granule treatment (all P<0.05). Mechanistically, increased P-ERK1/2 and decreased P-ERK5 levels were observed in myocardial tissues of mice treated with Adriamycin for 8 weeks. However, such signaling change could be partially corrected by Wenyangzhenshuai treatment. In addition, no significant difference was detected in the expression of ERK1/2 and ERK5 mRNA levels between adriamycin injection groups and Wenyangzhenshuai treatment groups (P>0.05), indicating an alteration in the activity/phosphorylation levels of these proteins instead of the transcription levels. CONCLUSION: we found a beneficial effect of Wenyangzhenshuai treatment in partially decelerating the progression of CHF. Such effect was probably through the role of Wenyangzhenchuan in diminishing p-ERK1/2 and raising p-ERK5 level in myocardial tissue. PMID- 26884997 TI - FAD-linked Presenilin-1 V97L mutation impede tranport regulation and intracellular Ca(2+) homeostasis under ER stress. AB - We report a PS1 gene mutation (Val 97Leu) in a Chinese familial Alzheimer's disease (FAD) pedigree and a cell model of FAD built by transfecting PS1 v97L mutants into human neuroblastoma SH-SY5Y cells. To test our hypothesis that the PS1 v97L mutation is pathogenic, we investigated possible alterations in transport regulation and intracellular Ca(2+) homeostasis in endoplasmic reticulum (ER). Grp78 is an ER-resident chaperone mediating the unfolded protein response (UPR) and is a key regulator of ER stress transducers. KDEL is a 4-amino acid retention sequence made of Lys-Asp-Glu-Leu-COO. KDEL is a "resident" sequence as protein residence in ER is consistently associated with KDEL at the C extremity. Our group used KDEL recognizing anti-Grp78 monoclonal antibody to detect the level of Grp78. We found increased KDEL level in all the transfected cells including cells transfected with PS1 V97L genes, wild-type and the mock. However cells with PS1 V97L mutation expressed a relatively lower KDEL compared with the wild-type and the mock, and a significantly lower Grp78 level compared with the wild-type, the mock and control. These results suggest that PS1 V97L mutation impedes intracellular transport regulation in ER. PS1 V97L mutation mediates increased ER Ca(2+) content in human neuroblastoma SH-SY5Y cells. The increased intracellular Ca(2+) release is due to depleted Ca(2+) storing content of ER but not due to extracellular environment as capacitative Ca(2+) entry (CCE) is invariant. PS1 V97L mutation interferes with intracellular Ca(2+) homeostasis. Abnormal transport regulation and Ca(2+) homeostasis attributed to PS1 V97L mutation may be associated with the pathology of Chinese familial FAD. PMID- 26884998 TI - Automated stroke volume and pulse pressure variations predict fluid responsiveness in mechanically ventilated patients with obstructive jaundice. AB - BACKGROUND AND OBJECTIVES: Stroke volume variation (SVV) and the pulse pressure variation (PPV) have been found to be effective in prediction fluid responsiveness especially in high risk operations. The objective of this study is to validate the ability of SVV obtained by FloTrac/Vigileo system and PPV obtained by IntelliVue MP System to predict fluid responsiveness in patients with obstructive jaundice during mechanical ventilation. METHODS: Twentyfive patients with obstructive jaundice (mean serum total bilirubin 175.0 +/- 120.8 MUmol/L), who accepted volume expansion and were hemodynamically stable after induction of anesthesia, were included in the study. SVV and PPV were recorded simultaneously before and after an intravascular volume expansion. Patients with a stroke volume index (SVI) increase of more than 10% after volume expansion were considered as responders. RESULTS: The agreement (mean bias +/- SD) between SVV and PPV was 0.2% +/- 1.56%. Before volume expansion, SVV and PPV were significantly higher in responders compared to non-responders (P<0.001, P<0.001). Significant correlation was observed between the baseline value of SVV and PPV and the percent change in SVI after fluid expansion (r=0.654, P<0.001; r=0.592, P=0.002). Area under the receiver operating characteristic curves of SVV (0.955) and PPV (0.875) were comparable (P=0.09). The optimal threshold values in predicting fluid responsiveness were 10% for SVV and 8% for PPV. CONCLUSION: In conclusion, SVV obtained by FloTrac/Vigileo system and PPV obtained by IntelliVue MP System was able to predict fluid responsiveness in patients with obstructive jaundice. PMID- 26884999 TI - Prognostic value of caveolin-1 in genitourinary cancer: a meta-analysis. AB - We aimed to obtain the most comprehensive picture to date of the prognostic value of caveolin-1 (Cav-1) in genitourinary carcinoma by meta-analyzing all eligible studies in PubMed and EMBASE. Data on patient clinical characteristics, cancer specific survival (CSS) and recurrence-free survival (RFS) were extracted. The meta-analysis included 6 articles on prostate cancer, 5 on renal cancer, 1 on bladder cancer and 1 on transition cell carcinoma of the upper urinary tract. Two studies examining the association of ELISA-measured Cav-1 levels in serum with RFS in 621 patients with prostate cancer gave a combined hazard ratio (HR) of 1.25 (95% CI 0.36 to 4.36). The other 4 studies on prostate cancer examined the association of immunohistochemically determined Cav-1 levels in cancerous tissue with RFS and gave a combined HR of 1.83 (95% CI 1.36 to 2.47). Three studies on renal cancer examining the association of Cav-1 levels with CSS gave a multivariate HR of 1.98 (95% CI 1.35 to 2.90). The single studies on bladder carcinoma and upper urinary tract carcinoma gave, respectively, a multivariate HR of 2.28 (95% CI 1.09 to 4.74) for the relationship of Cav-1 levels to DFS, and a multivariate HR of 5.08 (95% CI 1.799 to 14.342) for the relationship of Cav-1 levels to CSS. This meta-analysis of available evidence suggests that elevated Cav-1 levels in serum can predict poor survival in patients with genitourinary cancer, which may help identify high-risk patients earlier and guide clinical decision-making. PMID- 26885000 TI - Gastric emptying scan after distal subtotal gastrectomy: Differences between Billroth I and II and predicting the presence of food residue at endoscopy. AB - PURPOSE: We investigated whether gastric emptying scans (GESs) showed different emptying patterns between patients after different types of laparoscopic distal subtotal gastrectomies. We also investigated whether the presence of food residue via endoscopy can be predicted by GESs. MATERIALS AND METHODS: We retrospectively enrolled patients who had GESs within postoperative week 1 after a Billroth I or Billroth II operation. Diabetic patients were excluded. GESs were done with a solid test meal. Percent emptying at each scan time was analyzed. The presence of food residue in the stomach and gastrointestinal symptoms at the outpatient clinic were also analyzed. RESULTS: In total, 46 patients were enrolled (Billroth I: Billroth II = 21:25). Sixteen patients underwent a second GES (postoperative 3 6 months). Both groups showed delayed gastric emptying at the postoperative 1 week scan, but group I showed much slower emptying. However, this difference disappeared by the second scan. Based on endoscopies conducted 6 months after the operation, 73.2% of patients had significant amounts of food residue, which hindered an accurate evaluation. The proportion of patients with food residues did not differ between the groups. Receiver Operating Characteristic (ROC) curve analysis revealed that a cut-off value of <= 30% emptying at 100 min and 120 min in postoperative 3-6 month scans was both highly sensitive and specific for predicting the presence of food residue (90.91% and 75% for 100 min and 91.67% and 75% for 120 min, respectively). CONCLUSIONS: GESs within a week after distal subtotal gastrectomy show slower emptying of Billroth I than II. At a <= 30% emptying threshold, a GES can predict subtotal gastrectomy patients who might have a significant amount of food residue in their stomach even after following typical fasting instructions to prepare endoscopy. PMID- 26885001 TI - Recepteur d'Origine nantais (RON) tyrosine kinase splicing variants lacking exons 18 and 19 occur ubiquitously in lung cancer. AB - BACKGROUND: Aberrant expression of RON, a MET family receptor tyrosine kinase, has been correlated to tumor growth and metastasis. Intense research efforts are on to target RON using small molecule tyrosine kinase inhibitors or specific antibodies. However, progress towards specific targeting of RON is hampered by a lack of understanding of the nature and number of isoforms of RON expressed by tumors. We hypothesize that formation of different isoforms via alternative splicing may be fundamental to the tumor promoting functions associated with aberrantly expressed RON in cancers. METHODS: In this study, we analyzed the transcript sequence variations caused by alternative splicing in the C-terminal region of RON cDNA by PCR amplification and sequencing of five small cell lung carcinoma (SCLC) and seven non-small cell lung carcinoma (NSCLC) cell lines. RESULTS: Results revealed the presence of two alternatively spliced variants, each caused by unique exon(s) deletion: a previously known transcript variant lacking exon 19 and a novel one lacking exons 18+19. The two alternatively spliced variants together with the wild-type transcript were detected in each of the 12 lung cancer cell lines analyzed. Combined loss of exons 18+19 results in an in-frame deletion of 303 nucleotides corresponding to 101 amino acids of the tyrosine kinase domain. Translation products of transcript variants lacking exons 18 and 19 are expected to dominant negatively inhibit ligand stimulated RON signaling. CONCLUSIONS: The ubiquitous presence of alternatively spliced transcripts and their translation products may affect quantitative expression analysis, either by immunological or PCR methods, by interfering with estimation of normal RON, leading to exaggerated values. Besides, RON isoforms with dominant negative activities may interfere with siRNA based functional analysis of wild type RON. PMID- 26885002 TI - Ventriculoscopic surgery for arachnoid cysts in the lateral ventricle: a comparative study of 21 consecutive cases. AB - OBJECTIVE: To evaluate neuronavigation-guided ventriculoscopic technique in the treatment of arachnoid cysts in the lateral ventricle. METHODS: Between January 2008 to November 2011, twenty-one neuronavigationguided ventriculoscopic surgery were performed for the treatment of symptomatic arachnoid cysts in 21 patients (14 male and 7 female patients, mean age 24.1 years [ranged 1.5-61 years]) Clinical presentations varied from headache, vomiting, hemiparesis and seizure. The trajectory of ventriculoscopy was dynamically monitored and guided in real time by neuronavigation system. Cysts fenestrations were performed in fourteen cases, and cysts resection in seven cases, respectively. All patients were prospectively had a regular follow-up. RESULTS: After operation, all patients achieved symptom resolution without surgical mortality and morbidity. Aseptic meningitis was noted in four cases with cyst resection, and all recovered quickly without advanced treatments. However, a later ependymal adhesion, occurred in one case during follow-up period. CONCLUSION: The combination of ventriculoscopy and neuronavigation is an accurate, effective and safe approach for the treatment of the patients with arachnoid cysts in the lateral ventricle, especially, for overcoming the topographic variation caused by intraventricular pathologies. Cystoventriculostomy is the best choice. PMID- 26885003 TI - Association between alpha-1 antichymotrypsin gene A/T polymorphism and primary intracerebral hemorrhage: a meta-analysis. AB - The present study is to use meta-analysis to explain the association between alpha-1 antichymotrypsin (ACT) gene A/T polymorphism and the risk of primary intracerebral hemorrhage (PICH). Relevant studies before 1 June 2015 were identified by searching PubMed, Cochrane database and Science Citation Index Expanded (SCIE), and the references of retrieved articles. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to assess the strength of the association. Five independent publications, with 774 PICH cases and 940 controls, were included. There was no statistical evidence of association between ACT polymorphism and PICH risk under all genetic models in overall estimates (allele model: OR = 1.01, 95% CI = 0.80-1.28; heterozygote model: OR = 0.93, 95% CI = 0.60-1.45; homozygote model: OR = 1.03, 95% CI = 0.59 1.80; dominant model: OR = 0.97, 95% CI = 0.65-1.46; recessive model: OR = 1.06, 95% CI = 0.72-1.57). No association was found in subgroup analysis based on ethnicity, Hardy-Weinberg equilibrium, location of hematoma and blood pressure. Sensitivity analysis suggested that the combined results were stable and reliable. No significant publication bias was found by Begg's test and Egger's regression test. The results of our meta-analysis indicate that ACT polymorphism is unlikely to contribute to PICH susceptibility. PMID- 26885004 TI - Fast pinless external fixation for open tibial fractures: preliminary report of a prospective study. AB - A major drawback of conventional fixator system is the penetration of fixator pins into the medullary canal. The pins create a direct link between the medullary cavity and outer environment, leading to higher infection rates on conversion to intramedullary nailing. This study was designed to prospectively evaluate the role of new rapid pinless external fixators in primary stabilization of open tibial shaft fractures. In our study, a prospective study of 96 consecutive patients of open tibial shaft fractures treated with new rapid pinless external fixator and reamed intramedullary nail was carried out. The bone healing status, ability to maintain alignment were examined for radiologic outcome, whereas initial management, length of hospital stay, associated morbidity, range of knee and ankle motion, time to partial and full weight bearing, employment status and perioperative and postoperative complications were used for clinical evaluation. We followed up for over two years for the patients underwent clinical and radiologic after the surgery. The mean hospital stay was 15 days (ranges, 8-68). Bone healing was achieved for all cases except 3 patients who were lost to follow-up study. No patient suffered compartment syndromes. There was no statistically significance in range of motion among the knees of injury and uninjured limbs at final follow-up (P > 0.05). To the last follow-up, there were no cases of deep infection or implant-related fractures. Seventy-one patients who were employed before the injury returned to work after the operation, 16 had changed to less strenuous work. We concluded that better results can be achieved on clinical and radiologic evaluation of primary stabilization with rapid pinless external fixator and early exchange reamed intramedullary nail for suitable patients with open tibial shaft fractures. The incident rate of relative complications is low. The rapid pinless external fixator can be combined favorably with the reamed intramedullary nail and is a valuable addition to the conventional external fixator systems. PMID- 26885005 TI - Comparison on the efficacy of everolimus-eluting stent and zotarolimus-eluting stents in coronary heart disease between diabetic and non-diabetic patients. AB - OBJECTIVE: The aim of this study is to examine and compare the efficacy of everolimus-eluting stents (EES) and zotarolimus-eluting stents (ZES) in coronary heart disease in diabetic or non-diabetic patients. METHODS: A total of 666 patients needed for percutaneous coronary intervention were randomly selected from June 2008 to June 2013 in our hospital and were divided into two groups: (i) coronary heart disease with diabetes group and (ii) non-diabetes group. Patients in each group were further assigned to receive treatment of either EES or ZES. Then we observed the major adverse cardiac events, including mortality, nonfatal myocardial infarction and non-fatal cerebrovascular events over the period of 15 months after initial stent implantation. RESULTS: Compared to the non-diabetic group, more patients in diabetic group had received anti-hypotensive treatment (72% vs. 49%, P < 0.0001) and hypolipemic treatment (80% vs. 67%, P < 0.0001) before the percutaneous coronary intervention. In both diabetic group and non diabetic group, patients received ZES treatment had a much greater incidence rate of major adverse cardiac events compared to the patients received EES treatment (P < 0.05). Meanwhile, target lesion revascularization rate in the ZES group was also significantly higher than that in the EES group. The data showed big differences between ZES and EES groups with important statistical significance (P < 0.05). CONCLUSION: Patients with coronary heart disease and diabetes have a higher risk of major adverse cardiac events after stent implantation. EES treatment is safer with higher efficacy in our study, being a more effective stent for the patients merged with diabetes. PMID- 26885006 TI - Puerarin accelerate scardiac angiogenesis and improves cardiac function of myocardial infarction by upregulating VEGFA, Ang-1 and Ang-2 in rats. AB - OBJECTIVE: The traditional Chinese medicinal puerarin, has long been used to treat cardiovascular diseases, however, the mechanism underlying its effects remain unclear. Here, this study would to investigate the role of puerarin on cardiac angiogenesis and myocardial function induced by myocardial infarction. METHODS: Puerarin was treated in rats after left anterior descending coronary artery (LAD) ligation and maintained for 4 weeks (diets containing about 50 mg/kg/day or 100 mg/kg/day). After treatment, cardiac function was evaluated by echocardiography and markers of heart failure. Paraffin sections of the heart tissues were used for isolect in GS-IB4 staining. The Mrna and protein expression levels of VEGFA, Ang-1 and Ang-2 were detected by real-time polymerase chain reaction and western blot. RESULTS: Significantly damaged angiogenesis and slightly increase of VEGFA, Ang-1 and Ang-2 were showed after LAD ligation. Impaired angiogenesis and cardiac function were remarkably improved in puerarin treatment rats with great increase of VEGFA, Ang-1 and Ang-2. CONCLUSION: The above results demonstrated that puerarin could accelerate cardiac angiogenesis and improve cardiac function of myocardial infarction rats by upregulating VEGFA, Ang-1 and Ang-2. PMID- 26885007 TI - Pathological observation of acute myocardial infarction in Chinese miniswine. AB - The acute myocardial infarction (AMI) model in Chinese miniswine was built by percutaneous coronary artery occlusion. Pathological observation of AMI was performed, and the expression of tumor necrosis factor alpha (TNF-alpha) in the infarct sites was detected at different days after modeling in Chinese miniswine. The experimental findings may be used as the basis for blood flow reconstruction and intervention after AMI. Seven experimental Chinese miniswine were subjected to general anesthesia and Seldinger right femoral artery puncture. After coronary angiography, the gelfoam was injected via the microtube to occlude the obtuse marginal branch (OM branch). At 1 d, 3 d, 5 d, 7 d, 10 d, 14 d and 17 d after modeling, hetatoxylin-eosin (HE) staining was performed to observe the pathological changes and to detect the expression of TNF-alpha in the myocardial tissues. Cytoplasmic acidophilia of the necrotic myocardial tissues at 1 d after modeling was enhanced, and cytoplasmic granules were formed; at 3 d, the margins of the necrotic myocardial tissues were infiltrated by a large number of inflammatory cells; at 5 d, the nuclei of the necrotic myocardial cells were fragmented; at 7 d, extensive granulation tissues were formed at the margin of the necrotic myocardial tissues; at 10 d, part of the granulation tissues were replaced by fibrous scar tissues; at 14-17 d, all granulation tissues were replaced by fibrous scar tissues. Immunohistochemical detection indicated that no TNF-alpha expression in normal myocardial tissues. The TNF-alpha expression was first detected at 3 d in the necrotic myocardial tissues and then increased at 5 d and 7 d. After reaching the peak at 10 d, the expression began to decrease at 14 d and the decrease continued at 17 d. Coronary angiography showed the disappearance of blood flow at the distal end of OM branch occluded by gelfoam, indicating that AMI model was constructed successfully. The repair of the infarcted myocardium began at 10-17 d after modeling with safe blood flow reconstruction. TNF-alpha expression in the infarcted myocardium was the highest at 10 d, which can be explained by inflammation and repair of the infarcted myocardium. PMID- 26885008 TI - Levels of CEA, CA153, CA199, CA724 and AFP in nipple discharge of breast cancer patients. AB - The distinction between breast cancer and benign breast diseases with nipple discharge remains an important diagnostic challenge. The purpose of this study was to predict the potential usefulness of tumor markers in nipple discharge and to investigate the relationship of tumor markers and clinical characteristics with breast cancer.One hundred and eleven patients with nipple discharge received breast surgery from November 2013 to December 2014 were included in the study. We evaluated levels of five tumor markers (CEA, CA153, CA199, CA724 and AFP) prior to treatment. Patients were divided into two groups according to postoperative pathological results: 30 cases in breast cancer group and 81 cases in benign group. The relationships of clinical characteristics with breast cancer were investigated by multivariate analysis with a logistic regression model.It showed significant differences in levels of nipple discharge CEA (P < 0.001) and CA153 (P = 0.014), but not CA199 (P = 0.856), CA724 (P = 0.171), AFP (P = 0.834) among two groups. Logistic regression analysis demonstrated complaint, age, menopause, abnormal palpable mass, CEA and CA153 were associated with breast cancer. In summary, measurements of CA199, CA724 and AFP in nipple discharge are not of great clinical value. Detecting CEA and CA153 in nipple dischargecould potentially be used for the early detection of breast cancer with in high-risk populations. PMID- 26885009 TI - Antioxidant and antitumor effects of ferula sinkiangensis K. M. Shen. AB - OBJECTIVE: This study is to investigate the antioxidant and antitumor effects of the extract fractions of the Ferula sinkiangensis K. M. Shen. METHODS: Four different fractions of the Ferula sinkiangensis K. M. Shen were obtained by the extraction with petroleum ether, ethyl acetate, n-butanol, and methanol, respectively, which were used to treat the HCT116, Caco-2, HepG2, and MFC cells. Free radical scavenging effects of the ferula fractions were deteced with the DPPH assay. Effects of the ferula fractions on the peroliferatoin of the tumor cells were assessed with the SRB assay. Apoptosis was detected with flow cytometry. RESULTS: The DPPH assay showed that the petroleum ether fraction hardly showed any antioxidant activity, while the ethyl acetate, n-butanol, and methanol fractions exhibited free radical-scavenging capacities, in a dose dependent manner. The SRB assay showed that, the proliferation of the tumor cells could be inhibited by the ferula fractions, in a dose dependent manner. However, differential effects were observed for the different fractions in different model cells. Particularly, the ethyl acetate fraction exerted the most efficient inhibiting effects on the tumor cell proliferation. In addition, the flow cytometry showed that, all the ferula fractions significantly enhanced the apoptotic process in the tumor cells, with differential enhancing capacities in different model cells. CONCLUSION: Extract fractions of the Ferula sinkiangensis K. M. Shen could exert antioxidant, proliferation-inhibiting, and apoptosis enhancing effects in tumor cells. Particularly, the ethyl acetate fraction exhibits the most potent antioxidant and antitumor effects. PMID- 26885010 TI - The effect of sevoflurane on the cognitive function of rats and its association with the inhibition of synaptic transmission. AB - To observe the effects of different concentrations of sevoflurane on synaptotagmin 1 (Syt1) expression, synaptic long term depression (LTD), and paired pulse depression (PPD) in the rat hippocampus as well as to investigate the association between these effects and the cognitive function of rats. A total of 24 male Sprague-Dawley (SD) rats were selected and randomly divided into 3 groups: the control group (group A), which inhaled air; group B, which inhaled 0.65 minimum alveolar concentration (MAC) sevoflurane for 2 h; and group C, which inhaled 1.30 MAC sevoflurane for 2 h. The subsequent experiments were performed after one day. (1) Y maze tests were performed, and the expression of Syt1 in hippocampal tissues was detected using western blot. (2) The changes in LTD and PPD in rat hippocampal slices were examined using electrophysiological techniques. Compared to the control group, the cognitive function was decreased and Syt1 expression in the hippocampus was significantly decreased in rats in the 1.30 MAC sevoflurane inhalation group. After 60 min of low frequency stimulation, the amplitudes of population spike (PS) potentials in rat hippocampal slices were significantly decreased. After induction of PPD, the P2/P1 ratio was significantly increased. No indicators in the 0.65 MAC sevoflurane inhalation group showed any significant changes. Inhalation of high concentrations of sevoflurane significantly reduced Syt1 protein levels in the rat hippocampus, significantly inhibited the release of presynaptic neurotransmitters, and reduced the efficiency of synaptic transmission, thus causing memory impairment. PMID- 26885011 TI - The clinical application and efficacy of percutaneous kyphoplasty via unilateral pedicular approach guided by CT image measurement. AB - This study aimed to investigate the clinical application and efficacy of percutaneous kyphoplasty via unilateral pedicular approach with the reference of preoperative CT image data. 73 cases (a total of 112 vertebrae) with thoracic and lumbar osteoporotic vertebral compression fractures (OVCF) received in our department were collected in this study and underwent percutaneous kyphoplasty via unilateral pedicular approach directed by CT image measurement with the operative time and fluoroscopic times recorded. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess the pain status and functional activity before and after operation and at the last follow-up, while X ray and CT image were used to measure the height of the injured spinal middle column and kyphotic Cobb angle before and after operation. 73 cases (112 vertebrae) underwent percutaneous kyphoplasty successfully. Cement leakage occurred in 7 cases without obvious neurological symptoms, and they were followed up for 10 to 60 months with the average of 23 months; adjacent vertebral refractures occurred in 3 cases during the follow-up, and their symptoms were relieved after the second surgery. There was significant difference in the height of the injured spinal middle column and kyphotic Cobb angle before and after operation (P<0.05); there was significant difference in preoperative and postoperative VAS score and ODI values (P<0.05). Postoperative CT image data showed that puncture paths of the 110 vertebrae were consistent with preoperative ones sketched using the CT image, and the consistent rate of preoperative and postoperative measurement data was 98%. All patients could ambulate with brace within 2 days after operation without serious complications. In conclusion, percutaneous kyphoplasty via unilateral pedicular approach guided by preoperative CT image data is effective in treatment of osteoporotic vertebral compression fractures, and it is convenient and safe with high puncture accuracy, shorter operative time and less radiation exposure for patients and operators. PMID- 26885012 TI - Comparison of the treatment of hydrocolloid and saline gauze for pressure ulcer: a meta-analysis of randomized controlled trials. AB - PURPOSE: To determine the hydrocolloid dressing versus saline gauze for the treatment of pressure ulcer. METHODS: Pubmed and Web of Knowledge were searched for randomized controlled trials for the treatment of hydrocolloid and saline gauze for pressure ulcer. The random effect model was used. Sensitivity analysis and publication bias were conducted. RESULTS: Seven randomized controlled trials involving a total of 329 participants were included in this meta-analysis. The combined results suggested that significant association in complete healing were detected among hydrocolloid dressings and saline gauze [Summary RR=2.20, 95% CI=1.21-4.02, I(2)=48.5%]. The associations were also significant when we only combine the results for ulcers healed and the treatment duration of 8-12 weeks. No publication bias was found. CONCLUSIONS: Our meta-analysis suggested that the use of hydrocolloid dressing increased the likelihood of complete healing by more than two-fold compared with saline gauze dressing. PMID- 26885014 TI - Erbium: YAG laser (2,940 nm) treatment stimulates hair growth through upregulating Wnt 10b and beta-catenin expression in C57BL/6 mice. AB - AIM: To evaluate the role of 2,940 nm erbium: YAG laser in hair growth in C57BL/6 mice. METHODS: Anagen was experimentally induced by depilation. Healthy C57BL/6 mice (n=22) were randomly divided into four groups, with treatment of laser or minoxidil, or with combined laser and minoxidil treatments. The skin color of each mouse was observed each day. The time from telogen (pink skin color) to anagen (black coloration) phase and from anagen (black coloration) to catagen (all hairs grew out of the depilated skin) have been recorded. Hematoxylin and eosin (H&E) assay was done at fifteen days after the first treatment for each group to observe hair follicles and hair cycle score. Western blot analysis was utilized to detect the expression levels of Wnt 10-b and beta-catenin. RESULTS: Black pigmentation started significantly earlier both in the laser and combination group than in the control group. Moreover, the time from anagen to catagen in the laser, minoxidil and combination groups were all significantly shorter from the control group. Histopathology with H&E staining showed an obvious increase in the number of hair follicles in the anagen phase caused by the treatment of 2,940 nm erbium: YAG laser and minoxidil. Similarly, the percentage of hair follicles in anagen VI accounted for 19.5%, 37.5%, 41.5% and 44% in control, laser, minoxidil, and combination group, respectively. Western blot analysis showed that both the levels of Wnt 10b and beta-catenin were significantly increased by the treatment of 2,940 nm erbium: YAG laser. CONCLUSION: Our findings showed that 2,940-nm Er: YAG laser could promote hair growth by inducing hair cycle transition from telogen to anagen phases in C57BL/6 mice through up regulating Wnt 10b and beta-catenin. These results suggest that 2,940-nm Er: YAG laser may be a potential therapy for hair loss. PMID- 26885013 TI - FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4), and their combinations in the assessment of liver fibrosis in patients with hepatitis B. AB - OBJECTIVES: The aim of this study was to assess the effects of FibroScan, aspartate aminotransferase and alanine aminotransferase ratio (AAR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the 4 factor (FIB-4) and their combinations on liver fibrosis in patients with hepatitis B. METHODS: 406 hospitalized patients with chronic hepatitis B (CHB) and cirrhosis in our hospital were analyzed retrospectively and collected patients clinical indicators, including liver stiffness (LS), AAR, APRI and FIB 4, and then compared the differences of these indicators between CHB group and hepatitis B with cirrhosis group. Receiver operating curve (ROC) was used to evaluate the differentiating capacity of these indicators on CHB and liver cirrhosis. RESULTS: Four indicators related to liver cirrhosis had a statistical significance between two groups (P < 0.01); the under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of CHB and liver cirrhosis were 0.866, 0.772, 0.632 and 0.885, respectively. The under ROC curve areas of LS, AAR, APRI and FIB-4 for differential diagnosis of liver cirrhosis at compensatory stage and de-compensatory stage were 0.627, 0.666, 0.795 and 0.820, respectively. CONCLUSION: LS, AAR, APRI and FIB-4 were good indicators as clinical diagnosis and differential diagnosis on hepatitis B related cirrhosis. PMID- 26885015 TI - Stage I posterior osteotomy and instrumentation and stage II anterior debridement and bone grafting for lumbar spinal tuberculosis with severe kyphosis. AB - The purpose of this study was to determine the efficacy of stage I posterior osteotomy and instrumentation followed by stage II anterior debridement and bone grafting in patients with lumbar spinal tuberculosis (TB) with severe kyphosis. The records of patients with lumbar spinal TB and severe kyphosis treated with 2 stage surgery at our hospital from 2005 to 2010 were retrospectively reviewed. Outcome measures were kyphosis correction rate, visual analogue scale (VAS) pain scores, and American Spinal Injury Association (ASIA) spinal cord injury and sensation function scores. A total of 53 patients (34 male, 19 female; mean age 32 years) were included. The number of involved kyphosis segments ranged from 7 to 14, and the average preoperative kyphosis angle was 107.3 +/- 18.1 degrees . All procedures were performed without serious complications. The average follow up time was 42 months. Bone fusion occurred at a range of 6 to 9 months after surgery, and none of the patients had internal fixation failure, position change, or pseudoarthrosis. The mean postoperative kyphosis angle was 29.4 +/- 12.4 degrees , with a mean improvement of 77.9 degrees , and the correction rate was 72.6% (P < 0.001). At final follow-up, average correction loss was 1.35 degrees . The mean postoperative VAS pain score was 2.4 +/- 0.8, and the change from the preoperative value was significant (P < 0.001). ASIA spinal injury scores were increased postoperatively. Stage I posterior osteotomy and instrumentation followed by stage II anterior debridement and bone grafting can achieve good results in patients with lumbar TB and severe kyphosis. PMID- 26885016 TI - Association between HTR2A T102C polymorphism and major depressive disorder: a meta-analysis in the Chinese population. AB - Although a number of studies have been conducted on the association between HTR2A T102C polymorphism and major depressive disorder (MDD) in Chinese, this association remains elusive and controversial. To clarify the effects of HTR2A T102C polymorphism on the risk of MDD, a meta-analysis was performed in the Chinese population. Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) till 5 May 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. Statistical analyses were conducted with Version 10.0 STATA statistical software. A total of 12 case-control studies including 1444 MDD cases and 1445 controls were involved in this meta-analysis. Overall, no significant association with MDD risk was provided in the Chinese population (C vs. T: OR=0.97, 95% CI: 0.81-1.17, 95%; CC vs. TT: OR=0.95, 95% CI: 0.65-1.37; CC+TC vs. TT: OR=0.96, 95% CI: 0.75-1.12; CC vs. TT+TC: OR=0.94, 95% CI: 0.78-1.12). In subgroup analyses stratified by geographic area and source of controls, no significant association was found in any of the subgroups. In conclusion, this meta-analysis indicate that the HTR2A T102C polymorphism is not associated with susceptibility to MDD in Chinese population. PMID- 26885017 TI - Expression of HAX1 and Ki-67 in breast cancer and its correlations with patient's clinicopathological characteristics and prognosis. AB - OBJECTIVE: This study aimed to investigate the HS-1-associated protein X-1 (HAX1) and Ki-67 expression in the breast cancer and its clinical significance. METHODS: Breast cancer tissues and tumor-adjacent tissues were collected from 81 patients, and immunohistochemistry was conducted to detect the HAX1 and Ki-67 expression. The correlations of HAX1 expression with demographics, clinicopathological characteristics and prognosis were evaluated. RESULTS: HAX1 was highly expressed in the breast cancer, and its expression was related to the degree of breast cancer differentiation (P=0.002), lymph nodes metastasis (P=0.008) and progesterone receptor (PR) (P=0.021), but not with the age, tumor size, histological type, estrogen receptor (ER), HER2 and p53. HAX1 expression was positively related to Ki-67 expression in the breast cancer (r(2)=0.394, P=0.019). In addition, a higher HAX-1 expression was related to a lower 10-year survival rate. CONCLUSION: HAX1 is a new protein related to the breast cancer and probably plays an important role in the invasion and metastasis of breast cancer. Thus, HAX1 may be used as a potential target for the therapy of breast cancer. PMID- 26885018 TI - Association of osteopontin polymorphism with cancer risk: a meta-analysis. AB - To investigate the association of osteopontin gene -443 C>T, -156 G>GG, and -1748 A>G polymorphisms with cancer risk. The Medline, PubMed, PUBMED, EMBASE and Web of Science databases were searched. Meta-analyses were conducted using RevMan 5.2 software. After searching and evaluating the included papers, total 10 documents involved in -443 C>T, 8 papers involved in four articles involved in -156 G>GG and -1748 A>G were included into this meta analysis. There were no significant differences in genotype osteopontin -443 C>T distribution between cancer cases and control (OR=0.98, 95% CI=0.68-1.40, P=0.90; OR=0.90, 95% CI=0.60-1.35, P=0.62; OR=0.98, 95% CI=0.59-1.64, P=0.94; OR=0.87, 95% CI=0.60-1.25, P=0.44, respectively). Meanwhile, no association between osteopontin -1748 A>G polymorphism and tumors under all genetic models. (OR=0.73, 95% CI=0.54-1.00, P=0.05; OR=0.95, 95% CI=0.82-1.10, P=0.48; OR=1.31, 95% CI=0.95-1.81, P=0.10; OR=0.90, 95% CI=0.77-1.06, P=0.20, respectively). However, osteopontin -156 G>GG polymorphism is only partly related to the tumor risk. (GGGG+GGG vs GG model, OR=1.21, 95% CI=1.01-1.46, P=0.04; GGG vs GG model: OR=1.19, 95% CI=1.05-1.35, P=0.008, respectively) osteopontin gene polymorphisms, -443 C>T and -1748 A>G was not associated with cancer risk, but partly associated to tumor risk for -156 G>GG gene polymorphism. PMID- 26885019 TI - Predictive potential role of GSTs gene polymorphisms in the treatment outcome of advanced non-small cell lung cancer patients. AB - This study aimed to investigate the possible association between GSTP1, GSTM1, and GSTT1 polymorphisms and treatment outcome of advanced NSCLC. Between October 2009 and October 2011, a total of 308 patients of NSCLC on stage IIIA, IIIB or IV, treated with cisplatin-based chemotherapy were included. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the GSTP1 and GSTM1, and GSTT1 polymorphisms. We found that the IIe/Val and Val/Val genotypes of GSTP1 showed more CR+PR to chemotherapy in advanced NSCLC when compared with IIe/IIe genotype, and the Ors (95% CI) were 0.37 (0.18-0.71) and 0.15 (0.07-0.38). The IIe/Val and Val/Val genotypes of GSTP1 were associated with longer overall survival of advanced NSCLC when compared with the IIe/IIe genotype (For IIe/Val vs IIe/IIe, 37.63 +/- 2.01 months vs 30.25 +/- 2.06 months; for Val/Val vs IIe/IIe, 39.84 +/- 3.36 months vs 30.25 +/- 2.06 months). In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with advanced NSCLC, and the HRs (95% CIs) were 0.51 (0.28-0.94) and 0.35 (0.16-0.78), respectively. We found that the GSTP1 polymorphisms might affect the clinical outcome of patients with advanced NSCLC, and our results could help us to facilitate therapeutic decision for individualized therapy. PMID- 26885020 TI - Effects of down-regulation of clusterin by small interference RNA on human acute myeloid leukemia cells. AB - AIMS AND BACKGROUND: Up-regulation of clusterin is associated with the survival and progression of various malignancies, and down-regulation of clusterin promotes apoptosis and inhibits invasion. The aim of this study was to explore the effect of clusterin small interference RNA (siRNA) on the proliferation, apoptosis and invasion of HL-60 acute myeloid leukemia (AML) cells. METHODS: siRNA transfection was performed using LipofectamineTM2000 reagent. Relative protein expressions were quantified by Western blot. Trypan blue assay was performed to assess tumor cell proliferation after siRNA transfection. The cytotoxic effect of clusterin siRNA on leukemic cells was measured using MTT assay. Apoptosis was detected using fluorescence microscopy assay. Migration and invasion was detected after clusterin was silenced. RESULTS: Clusterin siRNA clearly lowered clusterin protein levels in a time- dependent manner, leading to marked inhibition of cell survival, proliferation and invasion. Furthermore, clusterin down-regulation significantly enhanced the extent of HL-60 apoptotic cells. CONCLUSIONS: Our results suggest that the down-regulation of clusterin by siRNA can effectively trigger apoptosis and inhibit the proliferation and invasion of leukemic cells. Therefore, clusterin siRNA may be a potent adjuvant in AML therapy. PMID- 26885021 TI - Experimental studies on islets isolation, purification and function in rats. AB - To develop a simple and effective method of islet isolation and purification in rats. Collagenase P was injected into pancreatic duct followed by incubation in water bath to digest the pancreas and isolate islet, then discontinuous gravity gradient purification was used to purify the islet. The purified islets were identified by dithizone staining. The viability of islets was assessed by fluorescence staining of acridine orange (AO) and propidium iodide (PI). The function of purified islets was determined by glucose-stimulated insulin release test and transplantation of rat with streptozocin-induced diabetes. 738+/-193 islets were recovered after purification. The average purity was 77+/-13%, the viability of islets was more than 95%. When inspected by glucose stimulation, the secreted insulin concentration was 24.31+/-5.47 mIU/L when stimulated by low concentration glucose and 37.62+/-4.29 mIU/L by high concentration glucose. There was significant difference between the two phases (P<0.05). The blood sugar concentration recovered to normal level after two days in the animals with islet transplantation. In conclusion, islets can be procured with good function and shape by using the method of injecting collagenase into pancreatic duct followed by incubation in water bath and purification using discontinuous gravity gradient. PMID- 26885022 TI - Association between sodium intakes with the risk of chronic kidney disease: evidence from a meta-analysis. AB - OBJECTIVE: Inconsistent results regarding the association between sodium intake and the risk of chronic kidney disease (CKD) have been reported. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of sodium with the risk of CKD. METHODS: Pertinent studies were identified by searching of PubMed and Web of Science. The random effect model was used to combine the results. Meta-regression and subgroups analyses were used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Egger's regression asymmetry test. RESULTS: Finally, 9 articles involving 5638 CKD cases were included in this meta-analysis. Pooled results suggested that highest sodium intake level versus lowest level was significantly associated with the risk of CKD [summary relative risk (RR) = 1.088, 95% CI = 1.009-1.193, I(2) = 78.1%], especially among Europe [summary RR = 1.097, 95% CI = 1.009-1.205], but not in the America. The association was also found in the prospective studies [summary RR = 1.096, 95% CI = 1.007-1.192], but not in the cross-sectional studies. No evidence of significant publication bias was found. CONCLUSIONS: Higher sodium intake might increase the risk of CKD. PMID- 26885023 TI - Remote ischemic precondition prevents radial artery endothelial dysfunction induced by ischemia and reperfusion based on a cyclooxygenase-2-dependent mechanism. AB - Ischemic preconditioning (IPC) and remote ischemic precondition (RIPC) are resistance to ischemia-reperfusion (IR) injury. They have common protective mechanism. Cyclooxygenase (COX)-2 participate in the mechanism of IPC. So, the purpose of this study was to determine whether RIPC protects endothelial function of radial artery in human against IR and whether COX-2 involves in this effect. Endothelial IR injury was induced by arm ischemia (20 min) and reperfusion. Flow mediated dilation (FMD) of the radial artery was measured before and after IR. RIPC (three 5-min cycles of ischemia of the contralateral arm) was applied immediately and 24 h before IR. All volunteers received the COX-2 inhibitor celecoxib (200 mg orally twice daily) for 5 days. On day 6, all subjects experienced the same studies as described. FMD was reduced by IR without administration of RIPC (P<0.0001). RIPC prevent this impairment of FMD immediately (P=NS) and at 24 h (P=NS). Nevertheless, the COX-2 inhibiter abolished protective effect of RIPC at 24 h (P=NS), but not immediately (P=0.001). After administration of the COX-2 inhibiter, post-IR FMD after RIPC performed immediately had significant increase than after RIPC performed at 24 h (P=0.001) and without administration of RIPC (P=0.003). The COX-2 inhibiter made post-IR FMD evidently decrease after RIPC performed at 24 h (P=0.002). RIPC prevents radial artery endothelial dysfunction induced by IR. This protective effect of RIPC in the late phase is mediated by a COX-2-dependent mechanism. PMID- 26885024 TI - The extended spectrum beta-lactamases (ESBL) and virulence genes of intestinal enteroaggregative Escherichia coli (EAEC) in healthy elderly individuals. AB - AIM: to analyze the detection rate of intestinal enteroaggregative Escherichia coli (EAEC) in healthy elderly (>=60 years) individuals in the Hangzhou area of China, and to investigate the extended spectrum beta-lactamases and virulence genes of EAEC. METHODS: Stool specimens provided by healthy elderly individuals were cultured on blood agar, SS, and MAC plates. The bacterial strains were identified using Vitek-2 Compact automatic microorganism identification system and mass spectrometry. The resistance phenotypes of the bacteria were determined using the double-disk synergy method. The resistance genes and the EAEC virulence gene, astA and aggR, were amplified by PCR and compared to the sequences available in Gen Bank. RESULTS: Among the 1050 healthy volunteers, the majority of bacteria were E. coli, accounting for 960 strains, with an ESBL-positive rate of 36.3% (348/960). The EAEC detection rate was 10% (96/960); among them, 84 strains were astA, the detection rate of which was 8.75%; 12 strains were aggR, the detection rate of which was 1.25%. The ESBL-positive rate of EAEC strains were 56.25% (54/96), all of which carried the CTX-M type, with the CTX-M-14 predominating at 66.7% (36/54). CONCLUSIONS: The ESBL-positive rate of intestinal E. coli in healthy elderly individuals in the Hangzhou area of China was higher than the rate detected in other regions of china; and there was a high rate of antibiotic resistance among the intestinal EAEC in healthy elderly individuals. The results of this study suggest that EAEC is not only a pathogenic bacteria detected in diarrhea patients, but can also be present in healthy individuals, and high-resistance clinical strains have spread to the healthy population in the Hangzhou area. So vigilance is critical. PMID- 26885025 TI - Direct measurement of reactive oxygen species in leukocytes during hemodialysis therapy. AB - OBJECTIVES: Both chronic kidney disease (CKD) and hemodialysis (HD) are reported to elevate oxidative stress. Available evidence for oxidative stress is indirect measurement of oxidative stress as accumulation of byproducts by reactive oxygen species (ROS). We aimed to examine the effect of CKD and HD on ROS levels in circulating leukocytes and to compare those with conventional oxidative stress marker, F2-isoprostane, in HD patients. METHODS: Using flowcytometry techniques, ROS levels in circulating leukocytes can be directly measured in 16 HD patients and 12 healthy volunteers. We also measured circulating F2-isoprostanes levels in both groups. RESULTS: HD patients demonstrated a significant increase in serum levels of F2-isoprostanes. The direct measurement of ROS levels in leukocytes showed increase in HD patients compared to the control; 1.91-fold in polymorphonuclear leukocytes (PMN), 1.06-fold in lymphocytes, and 1.35-fold in monocytes. Significant difference between the two groups could be observed only in PMN. The ROS levels in all three fractions of leukocytes showed negative correlations with serum F2-isoprostane levels but the ROS levels only in PMN showed significant correlation (r(2) = 0.774, P = 0.001). CONCLUSIONS: Our results indicate that direct measurement of the ROS levels in circulating leukocytes by flowcytometry is a useful method to examine oxidative stress during HD procedure. The ROS levels in circulating leukocytes showed negative correlation with serum F2-isoprostane levels. PMID- 26885026 TI - Deregulation of decorin and FHL1 are associated with esophageal squamous cell carcinoma progression and poor prognosis. AB - To investigate the expression of FHL1 and Decorin in esophageal squamous cell carcinoma (ESCC) and its clinical significance. 82 ESCC tissues were evaluated by immunohistochemistry for the expression of FHL1 and Decorin. The role of the expression of FHL1 and Decorin in ESCC were statistically analyzed. The expression level of FHL1 and Decorin were reduced in malignant tissue samples in comparison to normal matched tissue (P < 0.05). It was also proved that the positive expressions of FHL1 and Decorin were associated with ESCC histological grade, lymph node metastasis, tumor stage and clinical stage (P < 0.05). In addition, the Kaplan-Meier survival curves revealed that the positive expressions of FHL1 and Decorin were associated with favorable prognosis in ESCC patients. Multivariate analysis showed that the positive expressions of FHL1 and Decorin were independent prognostic markers of overall survival of ESCC patients, respectively. The positive expressions of FHL1 and Decorin were associated with ESCC progression and good prognosis. Our results indicate that the positive expressions of FHL1 and Decorin were independent prognostic factors for patients with esophageal cancer, which might be potential valuable biomarkers for ESCC. PMID- 26885027 TI - Prognostic significance of tissue miR-345 downregulation in non-small cell lung cancer. AB - BACKGROUND: MiRNAs might function as oncogenes or tumor suppressor genes in the tumorigenesis process. Dysregulation of miR-345 is a frequent event in many types of human cancers. However, the tissue miR-345 expression level in non-small cell lung cancer (NSCLC) and its potential clinical significance remains unknown. MATERIALS AND METHODS: Real-time PCR was conducted to evaluate the expression level of miR-345 in NSCLC tissues as well as cell lines. Then the association between tissue miR-345 expression level and clinical outcome was investigated. RESULTS: The expression level of miR-345 was significantly decreased in NSCLC tissues and cell lines compared with the controls (P<0.05; P<0.01). Tissue miR 345 expression level was associated with various clinicopathological parameters including LN metastasis (P=0.012), distant metastasis (P=0.007), TNM stage (P=0.008) and grade (P=0.030). In addition, the NSCLC patients in thelow tissue miR-345 expression group had significantly shorter 5-year overall survival time than those in the high tissue miR-345expression group (P=0.016). Multivariate analysis showed that tissue miR-345 was an independent risk factor for NSCLC (HR=3.921, 95% CI: 2.285-10.540; P=0.008). CONCLUSIONS: The expression level of miR-345 was reduced in NSCLC tissues and cell lines. Low tissue miR-345 expression was associated with progression and poor prognosis of NSCLC, indicating that tissue miR-345 may serve as a novel prognostic marker in NSCLC. PMID- 26885028 TI - Ginkgo biloba extract induce cell apoptosis and G0/G1 cycle arrest in gastric cancer cells. AB - OBJECTIVE: Previous studies have shown that the Ginkgo biloba extract (EGb761) can be used to anti-cancer. However, the mechanism by which EGb761 mediate this effect is still unclear. In the present study, EGb761 inhibited cell proliferation and induced cell apoptosis in gastric cancer cell was explored. METHODS: The cell viability was detected by the CCK8 assay. The cell cycle and apoptosis was assessed by flow cytometry. The protein expression of caspase-3, p53 and Bcl-2 were analyzed by western blot. RESULTS: Treatment of human gastric cancer cells with EGb761 induced cell death in a dose-dependent manner by using CCK8 assay. Consistent with the CCK8 assay, the flow cytometry results showed that gastric cancer cells were accumulated in G0/G1 phase when exposed to EGb761. Furthermore, the proportion of apoptosis cells was increased after EGb761 treatment as compared to untreated group. In addition, our results showed that the treatment of AGS cells with EGb761 significantly increased the expression of caspase3 and p53, and decreased the anti-apoptotic Bcl-2 level. CONCLUSIONS: Our results demonstrated that EGb761 could inhibit gastric cancer proliferation through adjusting cell cycle and inducing cell apoptosis. PMID- 26885029 TI - Hirudin inhibits cell growth via ERK/MAPK signaling in human glioma. AB - Glioma is one of the most common intracranial tumors, and the prognosis is poor though more and more treatments are employed. ERK/MAPK signaling has been reported to be associated with glioma. In the present study, we aimed to investigate hirudin as an antineoplastic drug inhibits ERK/MAPK signaling in glioma growth in vitro. The cell proliferation and apoptosis rate were detected using MTS and Annexin V staining assay, cell cycle distribution was detected using flowcytometry assay. Furthermore, the relevant molecules of ERK/MAPK signaling were examined using Western blot analysis and immunofluorescence staining assay. We provide the first evidence that hirudin increase inactivation state of ERK1/2, down-regulate the expression of canonical ERK/MAPK signaling pathway and establish an important role for hirudin in the treatment of glioma cells. PMID- 26885030 TI - Immunohistochemistry and microsatellite instability analysis in molecular subtyping of colorectal carcinoma based on mismatch repair competency. AB - Mismatch repair defective (MMRd) colorectal carcinoma (CRC) is a distinct molecular phenotype of colorectal cancer, including 12% of sporadic CRC and 3% of Lynch Syndrome. In order to investigate the clinicopathological characteristics of MMRd colorectal carcinoma, and to find the most effective method for preliminary screening, 296 CRC fulfilled revised Bethesda Guideline (RB) were selected from 1450 CRCs to perform both IHC staining for MLH1, MSH2, MSH6, PMS2 and MSI analysis. Sixty-eight tumors were classified as MSI-H by MSI test. Colorectal carcinomas with MSI-H were prone to be proximal located, poorly differentiated, and relatively early staged, with infrequent metastasis to lymph node as well as to distant organs, compared with MSS ones. All of the 68 MMRd CRCs presented abnormal expression of at least one mismatch repair protein (MMRP), with 48 concurrent negative of MLH1 and PMS2, 14 concurrent negative of MSH2 and MSH6, 4 isolated negative of MSH6, 1 isolated negative of PMS2, and 1 concurrent negative of 4 MMRPs. All of the MLH1 negative tumors also showed abnormal expression of PMS2. All of the MSH2 negative cases also presented negative expression of MSH6. The sensitivity and specificity of the 2-antibody IHC test contained only PMS2 and MSH6 for screening for MMRd CRC were 100% and 98.2% respectively, exactly the same as that of the 4-antibody IHC test with all of the 4 MMRPs. The diagnostic accordance rate of the 2-antibody approach and MSI analysis was 98.6%. In conclusion, MMRd CRC has characteristic clinicopathological features different from MSS CRCs. The 2-antibody IHC approach containing MSH6 and PMS2 is the most easy and effective way to detecting MMR deficiency in CRC. PMID- 26885031 TI - Association of 8q23-24 region (8q23.3 loci and 8q24.21 loci) with susceptibility to colorectal cancer: a systematic and updated meta-analysis. AB - BACKGROUND: Several single nucleotide polymorphisms (SNPs), rs16892766 in the 8q23.3 region and rs6983267, rs10505477, rs7014346 and rs7837328 in the 8q24.21 region, have been identified by genome-wide association studies (GWAS) and a number of case-control studies to be closely associated with risk of colorectal cancer (CRC). In the present study, a meta-analysis was performed to confirm if these loci are risk factors for susceptibility to CRC, taking heterogeneity of population into consideration. METHODS: The whole literature search was conducted via database of MEDLINE and Embase, through which 33 articles with 49 studies (141,899 cases and 157,536 controls) were finally included in this meta-analysis to evaluate the association between the 5 polymorphisms and risk of CRC under allelic model. RESULTS: A meta-analysis of the pooled data showed that the G allele of rs6983267, the A allele of rs7014346, the T allele of rs10505477, the C allele of rs16892766 and the A allele of rs7837328 were associated with significantly increased risk of CRC under allelic model. Additionally, subgroup analyses of four SNPs (rs7837328 excluded) by ethnicity witnessed a notable association between the G allele of rs6983267 and increased risk of CRC among Caucasians, Asians and Africans. Furthermore, the C allele of rs16892766 was strongly linked with elevated risk of CRC among Caucasians and Africans. However, the A allele of rs7014346 and T allele of rs10505477 only heightened risk for CRC among Caucasians and showed no effects among Asians. CONCLUSION: In summary, rs6983267 is a risk factor for CRC among Caucasians, Asians and Africans; rs7014346 and rs10505477 are risky genetic polymorphisms only among Caucasians; rs16892766 is a hazardous element among populations with Caucasian and African ancestry; and rs7837328 could elevate the susceptibility to CRC in a multinational group. However, more potential factors related with CRC risk should be investigated in further studies. PMID- 26885032 TI - A cross-sectional study to estimate associations between education level and osteoporosis in a Chinese postmenopausal women sample. AB - BACKGROUND: Our research aims to investigate the associations between education level and osteoporosis (OP) in Chinese postmenopausal women. METHODS: A large scale, community-based, cross-sectional study was conducted to examine the associations between education level and OP. A self-reported questionnaire was used to access the demographical information and medical history of the participants. A total of 1905 postmenopausal women were available for data analysis in this study. Multiple regression models controlling for confounding factors to include education level were performed to investigate the relationship with OP. RESULTS: The prevalence of OP was 28.29% in our study sample. Multivariate linear regression analyses adjusted for relevant potential confounding factors detected significant associations between education level and T-score (beta = 0.025, P-value = 0.095, 95% CI: -0.004-0.055 for model 1; and beta = 0.092, P-value = 0.032, 95% CI: 0.008-0.175 for model 2). Multivariate logistic regression analyses detected significant associations between education level and OP in model 1 (P-value = 0.070 for model 1, Table 5), while no significant associations was reported in model 2 (P value = 0.131). In participants with high education levels, the OR for OP was 0.914 (95% CI: 0.830 1.007). CONCLUSION: The findings indicated that education level was independently and significantly associated with OP. The prevalence of OP was more frequent in Chinese postmenopausal women with low educational status. PMID- 26885033 TI - Cytochrome P450 2C9 (CYP2C9) polymorphisms in Chinese Li population. AB - BACKGROUND: The frequencies of Cytochrome P450 2C9 (CYP2C9) genotypes were various between populations. The aim of this study was to investigate the frequencies of the major variants of the CYP2C9 in Chinese Li minority populations. METHODS: The promoter, exons and surrounding introns, and 3' untranslated region of the CYP2C9 gene was detected by DNA sequencing to investigate in 100 unrelated healthy Chinese Li subjects. The protein function prediction was used the online tools: Sorting Intolerant From Tolerant (SIFT) and Phenotyping Version 2 (PolyPhen-2). The comparison of CYP2C9 allele frequencies in different populations were analyzed by Chi-square (chi(2)) test. Linkage disequilibrium (LD) analysis was performed using Haploview software. RESULTS: We identified 17 different CYP2C9 single nucleotide polymorphisms (SNPs) in the Li population, including two missense mutations (3549 G > A and 42614 A > C) and two silent mutations (3514 T > Cand 50298A > T). The protein function prediction revealed the two missense mutations result in protein damaging. In addition, we detected the allele frequencies of CYP2C9*1, CYP2C9*3 and CYP2C9*42 were 98%, 1%, and 1%, respectively. Finally, we compared three major allelic frequency (CYP2C9*1, CYP2C9*2, and CYP2C9*3) between Li and other populations. We found that our results were similar to East Asians and Africans. PMID- 26885034 TI - (18)F-Fluorodeoxyglucose positron emission tomography/computed tomography in patients with Kikuchi-Fujimoto disease: a nine-case series in China. AB - This study observed the image characteristics and clinico-imaging relationships of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in the patients with Kikuchi-Fujimoto disease (KFD). Nine consecutive patients with histologically proven KFD who underwent (18)F-FDG PET/CT were recruited. The (18)F-FDG uptakes of bone marrow (BM), spleen and lymph nodes (LNs) were systematically evaluated and maximum standardized uptake values (SUVmax) were measured. The number, locations and size factors of LNs were also assessed. The correlations were calculated between (18)F-FDG uptake and laboratory data and size factors of LNs, and the findings of LNs were compared between subgroups with different clinical features. (18)F-FDG uptakes were positive in the BM (SUVmax, 3.2 +/- 1.2), spleen (SUVmax, 2.8 +/- 0.7) and 122 affected LNs (SUVmax, 4.2 +/- 2.2) for all patients. The affected LNs presented a systemically (region, 4 +/- 1), multiple (number, 14 +/- 5) and small-sized (long axis diameter, 11.4 +/- 2.7 mm; short axis diameter, 8.0 +/- 2.1 mm; area, 81.1 +/- 44.6 mm(2)) pattern. The SUVmax of BM correlated to neutrophil count, and the SUVmax of affected LNs correlated to size factors and was lower in patients with long imaging interval and positive anti-nuclear antibody (ANA) (P < 0.05). We conclude that (18)F-FDG PET/CT can be characterized by the generalized distribution of relatively small-sized LNs and involvement of BM and spleen with high (18)F-FDG avidity in patients with KFD. The imaging interval, neutrophil count and ANA level should be synthetically considered during imaging evaluation. PMID- 26885035 TI - Combined portal vein resection for hilar cholangiocarcinoma. AB - BACKGROUND: Surgery is the only curative therapy for patients with hilar cholangiocarcinoma (HCCA). Combined portal vein resection (PVR) could achieve negative resection margins in HCCA patients with portal vein invasion. This systematic review aimed to analysis the efficiency of combined PVR for HCCA. METHODS: MEDLINE, EMBASE, the Cochrane Library, the Chinese National Knowledge Infrastructure database, and clinical trial registries were searched through April 2015. Risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. RESULTS: The analysis included 21 retrospective studies, altogether involving 2403 patients (patients with PVR, n=637; patients without PVR, n=1766). Patients with PVR were likely to have more advanced HCCA (lymphatic invasion: RR=1.14, 95% CI 1.02 to 1.28; perineural invasion: RR=1.31, 95% CI 1.05 to 1.63) and suffered less curative resections (RR=0.89, 95% CI 0.75 to 0.99). Postoperative morbidity was similar between patients with or without PVR (RR=1.06, 95% CI 0.94 to 1.02). Patients with PVR suffered higher mortality rate (RR=1.52, 95% CI 1.06 to 2.18), and worse 5-year survival rate (RR=0.67, 95% CI 0.49 to 0.91). CONCLUSION: Combined PVR for HCCA patients would not increase postoperative morbidity rate. However, ascribed to PVR group concluded more advanced HCCA patients; patients with PVR had increased postoperative mortality rate and worse survival rate. The results still need further high quality trails for validation. PMID- 26885036 TI - Percutaneous nephrolithotomy in prone position in patients with spinal deformities. AB - INTRODUCTION: The feasibility, safety and efficacy of percutaneous nephrolithotomy (PCNL) in patients with spinal deformities were evaluated and the results of a single centre experience were reported. PATIENTS AND METHODS: Between July 1999 and December 2014, 16 patients with spinal deformities underwent PCNL. The anomalies included 5 cases with kyphoscoliosis, 4 with post polio syndrome, 3 with osteogenesis imperfecta, 3 with myotonic dystrophy, and 1 with ankylosing spondylitis. All patients were preoperatively evaluated by an intravenous urogram and computerized tomography to assess the anatomy and appropriate access. The operative details, stone clearance rates, and complications were retrospectivelyanalyzed. RESULTS: A total of 16 standard PCNL procedures were performed on 16 renal-units. The mean age of the patients was 30.7 +/- 17.2 (5-62) years, and the mean stone burden was 609.6 +/- 526.9 (100 1800) mm(2). The mean operative and fluoroscopy times were 76.6 +/- 35.1 (35-150) minutes and 12.5 +/- 8.5 (3-34) minutes, respectively. At the end of the surgery, 13 (81.2%) of the patients were stone free. The overall success rate was 93.7% with the inclusion of 2 patients with clinically insignificant residual fragments (<3 mm). Complications (31.2%) included haemorrhage requiring a transfusion in 2 patients, prolonged urine leakage requiring double J catheter insertion in 1, infection in 1, and nephrectomy due to bleeding in 1. Mean hospitalization time was 4.6 +/- 2.4 (3-13) days. CONCLUSION: PCNL is an effective, safe and minimally invasive procedure for the treatment of kidney stones in patients with spinal deformities, and it can be performed with low morbidity and high success rates. To achieve better results and minimizing the risk factors, systematic and anatomic evaluations for anaesthesia and operative planning are crucial before surgery. PMID- 26885037 TI - Optimized combination therapies with adefovir dipivoxil (ADV) and lamivudine, telbivudine, or entecavir may be effective for chronic hepatitis B patients with a suboptimal response to ADV monotherapy. AB - OBJECTIVE: To identify high risk factors in chronic hepatitis B (CHB) patients for suboptimal response to adefovir dipivoxil (ADV) monotherapy, and to assess the efficacy of optimized therapy combining ADV with lamivudine (LAM), telbivudine (LdT), or entecavir (ETV) in patients with a suboptimal response to ADV alone. METHODS: Suboptimal response to ADV monotherapy was defined as having a decline in serum hepatitis B virus (HBV) DNA level of more than 1 log compared to baseline, but with viremia still detectable (HBV DNA >= 100 IU/mL), after 48 weeks of therapy. All patients who received ADV monotherapy in our clinic were analyzed retrospectively. Both univariate and multivariate logistic regression models were applied for risk factor analysis. Patients who showed suboptimal response completed at least 12 months of optimized combination therapy consisting of ADV plus LAM, ADV plus LdT, ADV plus ETV, or continuous ADV monotherapy. The primary outcome measurement was complete viral suppression, indicated by a reduction of HBV DNA to undetectable levels (CVS, with HBV DNA < 100 IU/mL). Secondary outcome measures were HBeAg seroconversion for HBeAg-positive patients, HBsAg loss, alanine aminotransferase (ALT) normalization and virological breakthrough rates. RESULTS: Of 521 patients who received ADV monotherapy, 170 showed a suboptimal response. These were grouped for continued therapy as follows: 34 in group A (continuous ADV monotherapy), 55 in group B (ADV plus LAM), 38 in group C (ADV plus LdT), and 43 in group D (ADV plus ETV). Using a logistic model, five conditions were identified as high risk factors for suboptimal response: presence of the tyrosine-methionine-aspartate-aspartate (YMDD) HBV DNA polymerase mutation; being HBeAg positive; having a high baseline level of HBV DNA; having a primary virological non-response to ADV; and [initial virological response] to ADV. After 48 weeks of ADV monotherapy, there were no withdrawn patients who had experienced side effects. The median HBV DNA levels were (4.4+/-1.3) log, (4.6+/-1.3) log, (4.7+/-1.4) log, and (4.5+/-1.5) log in groups A, B, C, D, respectively (F = 0.228, P = 0.876). After 48-weeks of continued ADV monotherapy or optimized combination therapy, the CVS rates were 23.5% (8/34), 60% (33/55), 52.6% (20/38), and 58.1% (25/43), respectively (chi(2) = 12.952, P = 0.005). The median HBV DNA declines were (0.5+/-1.7) log, (2.0+/ 1.3) log, (1.8+/-1.6) log, and (1.8+/-1.5) log, respectively (F = 6.775, P < 0.001). Virologic breakthrough rates were 26.5% (9/34), 7.3% (4/55), 10.5% (4/38), and 9.3% (4/43), respectively (chi(2) = 8.057, P = 0.045). CONCLUSION: Optimized combination therapies consisting of ADV plus LAM, LdT, or ETV may be reasonable choices for hepatitis B patients with a suboptimal response to ADV monotherapy. PMID- 26885038 TI - Elevated expressions of serum miR-15a, miR-16, and miR-17-5p are associated with acute ischemic stroke. AB - Acute ischemic stroke (AIS) is one of the leading causes of death and disability worldwide. Circulating microRNAs (miRNAs) have been identified as potential biomarkers in the diagnosis and prognosis of multiple human diseases including AIS. In this study, serum expression levels of miR-15a, miR-16, and miR-17-5p were detected in AIS patients (n = 106) and healthy controls (n = 120) using quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analyses were performed to investigate the associations between miRNA levels and AIS risk. The serum expression levels of miR-15a, miR-16, and miR-17-5p increased by 8.3 fold (P = 0.0104), 42 fold (P < 0.0001), and 9.9 fold (P = 0.0002) in AIS patients compared to controls, respectively. Multivariate logistic regression demonstrated that serum miR-17-5p level was a significant and independent predictor for determining the presence of AIS. Receiver operating characteristic (ROC) analysis revealed areas under the curves (AUCs) of 0.698 (95% confidence interval [CI]: 0.559-0.837, P = 0.01), 0.82 (95% CI: 0.71-0.931, P < 0.001), and 0.784 (95% CI: 0.666-0.903, P < 0.001) for miR-15a, miR-16, and miR-17-5p, respectively, while the AUC increased to 0.845 (95% CI: 0.74-0.949, P < 0.001) for the combination of these three micoRNAs. Our findings indicate that elevated serum expression of miR-15a, miR-16, and miR-17-5p is strongly associated with AIS and that the combination of these three microRNAs may be a promising serum biomarker for AIS. PMID- 26885039 TI - Characteristics of bacterial vaginosis infection in cervical lesions with high risk human papillomavirus infection. AB - High risk human papillomavirus (HPV) infection is the major cause of cervical cancer. Bacterial vaginosis (BV) is considered as the most prevalent vaginal imbalance affecting women of reproductive age. However, the relationship between HPV and BV infection is unclear. This study aimed to assess the prevalence of human papillomavirus (HPV) infection combined with bacterial vaginosis (BV) infection in Shanghai suburbs and evaluate associations between bacterial vaginosis with HPV infection, cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: From October 1, 2009 to October 31, 2013, a total number of 3502 women who visited Fengxian Hospital, Southern Medical University were enrolled in this study. All participants gave informed consent and agreed to HPV, BV, chlamydia, mycoplasma and thinprepcytologic test (TCT). In addition, all women took histopathologic examination under colposcopy. Statistical analyses were done using SPSS 17.0 for windows (IBM). In present study the overall BV positive rate was 9.25%. The top three high risk HPV types were listed as follows (in descending order): HPV16, 52, 58. Moreover, our data showed BV infection tended to occur in the HPV positive women, HPV infection also tended to occur in the BV positive women. Most of the women who present HPV with BV infection were younger than 30 years old. We also found that CIN and cervical cancer occurred mainly in HPV/BV positive and HPV with BV positive group. BV infection and HPV infection may haveconsistency or synergies. HPV with BV infection may increase the incidence of CIN and cervical cancer. PMID- 26885040 TI - Higher plasma level of STIM1, OPG are correlated with stent restenosis after PCI. AB - OBJECT: Percutaneous Coronary Intervention (PCI) is one of the most effective treatments for Coronary Heart Disease (CHD), but the high rate of In Stent Restenosis (ISR) has plagued clinicians after PCI. We aim to investigate the correlation of plasma Stromal Interaction Molecular 1 (STIM1) and Osteoprotegerin (OPG) level with stent restenosis after PCI. METHODS: A total of 100 consecutive patients with Coronary Heart Disease (CHD) received PCI procedure were recruited. Coronary angiography was performed 8 months after their PCI. Then patients were divided into 2 groups: observation group was composed by patients who existing postoperative stenosis after intervention; Control group was composed by patients with no postoperative stenosis. The plasma levels of STIM, OPG in all patients were tested before and after intervention. Pearson correlation and multiple linear regression analysis were performed to analysis the correlation between STIM, OPG level and postoperative stenosis. RESULTS: 35 cases were divided into observation group and other 65 were divided into control group. The plasma levels of STIM, OPG have no statistical difference before their PCI procedure, but we observed higher level of High-sensitivity C-reactive protein (Hs-CRP) existed in observation group. We observed higher level of plasma STIM, OPG in observation group when compared with control group after PCI procedure (P < 0.05). Regression analysis demonstrated that Hs-CRP, STIM1, OPG are independent risk factors for ISR. CONCLUSION: Elevated levels of plasma STIM1, OPG are independent risk factors for ISR in patients received PCI, which could provide useful information for the restenosis control after PCI. PMID- 26885041 TI - Expression of Beclin1 in the colonic mucosa tissues of patients with ulcerative colitis. AB - To investigate the expression of Beclin1 in the colonic mucosa tissue of patients with ulcerative colitis (UC), which acts as a regulator of autophagy and might play a part in the disease progression potentially. A total of 112 patients were selected from September 2013 to November 2014, and their colonic mucosal tissues were collected as the subject of study. Among them, 75 cases were diagnosed with ulcerative colitis (UC), 37 cases were diagnosed with irritable bowel syndrome (IRS) during the same time, which was set as the control group. The mucosal tissues were processed with ELISA and IHCA to measure the expression level of Beclin1, and correlation analysis was performed to demonstrate its role in the disease progression. The expression level pf Beclin1 was significantly higher in the UC patients compared with the control group (P<0.05). Meanwhile, it's positively correlated with the severity of disease, the endoscopic classification and the pathologic staging results, which has statistical significance (P<0.05). Beclin1 was expressed at a higher level in UC patients, and correlated with the severity of the disease, indicating the abnormal regulation of autophagy in the disease progression. PMID- 26885043 TI - On clipping of anterior communicating artery aneurysm via eyebrow-lateral keyhole approach. AB - OBJECTIVE: To evaluate the application of eyebrow-lateral keyhole approach in clipping of anterior communicating artery aneurysm (ACAA) through observing the therapeutic effect of eyebrow-lateral keyhole approach on ACAA. METHODS: In 37 patients with ACAA, cisterns were exposed via the eyebrow-lateral keyhole approach to reveal ACAA complex followed by clipping of ACAA. Of the 37 patients, external ventricular drainage was performed on 5 patients before microsurgery. All patients underwent head CT angiography on the second day after operation. RESULTS: Clipping of ACAA was successful in all patients at the first time. In 3 patients, ruptured aneurysm occurred during operation. Three patients underwent ventriculoperitoneal shunt because of postoperative hydrocephalus. Two patients had one-sided anterior cerebral artery infarction after operation. No patient died during operation. Follow-up after the operation indicated that 26 patients returned to normal life and work, 6 patients were able to look after themselves, 4 patients required care in their daily life and one patient died. CONCLUSION: The eyebrow-lateral keyhole approach is a preferred choice for surgical treatment of ACAA because it can cope with brain swelling and intraoperative ruptured aneurysm. However, it has a certain range of application, so we must strictly follow its indications. PMID- 26885042 TI - Dynamic changes of circulating T-helper cell subsets following severe thoracic trauma. AB - Major trauma induces profound immune dysfunction, which subsequently results in sepsis and multiple organ dysfunction syndromes (MODS). The functionally conducive immune cells are of paramount important in the early recovery and development of the post-traumatic organ failure. In this study, we investigated the immune deregulation after severe trauma by means of detecting the differentiation of CD4(+) T cells. Seven male patients with thoracic trauma (aged 29.8 +/- 7.6 years) hospitalized in the Intensive Care Units (ICU) in our hospital were enrolled in the study. Peripheral blood was collected from all the patients on the 1st, 7th, 14th and 21st day of admission, respectively. Flow cytometry was carried out to determine the percentage of CD4(+) T cells differentiated into Th1, Th2, Th17 and Treg subsets, based on which the ratios of Th1/Th2 and Th17/Treg were also calculated. Twenty-five healthy male individuals (aged 34 +/- 7 years) in the hospital in the same period of time served as controls. The frequencies of all the four subsets in the traumatic patients showed significant dynamic changes compared with those of the controls at the defined time points. The ratios of Th1/Th2 and Th17/Treg showed significant decrease at the study interval. Notably, the value of Th1/Th2 was significantly higher (P=0.004) in the trauma group than that of control group on the 1st day after admission, which was reversed on the 14th day (P=0.014). The imbalance of Th1/Th2 and Th17/Treg at the present study all reflected the immune dysfunction of CD4 T cells followed by the severe thoracic trauma. PMID- 26885044 TI - The association between serum uric acid and metabolic syndrome among adolescents in northeast China. AB - PURPOSE: Data about the association between serum uric acid and metabolic syndrome in healthy adolescents are sparse. This study examined this association and determined the optimal cutoffs for serum uric acid to predict metabolic syndrome among healthy adolescents. METHODS: During 2010-2011, we conducted a cross-sectional study of 927 adolescents (53.0% boys) aged 11-16 years from junior and senior high schools in northeast China. All participants received a physical examination and gave venous blood samples. RESULTS: Serum uric acid was positively associated with abdominal obesity, dyslipidemia and hypertension in boys and with abdominal obesity and dyslipidemia in girls. For those with hyperurecemia, the odds ratios (95% CI) for metabolic syndrome were 7.67 (95% CI, 2.58~22.78) for boys and 4.77 (95% CI, 1.01~22.60) for girls. SUA was a better predictor of metabolic syndrome than fasting glucose, though not as good as waist circumference. CONCLUSIONS: Among adolescents in China, serum uric acid level may be a useful predictor of metabolic syndrome. PMID- 26885045 TI - The relationship of frequency of meat consumption and osteoporosis in Chinese postmenopausal women. AB - BACKGROUND: This study was aimed at evaluating the associations between frequency of meat food intake and osteoporosis (OP) in general Chinese postmenopausal women. METHODS: We conducted a large-scale, community-based, cross-sectional study to investigate the associations by using self-report questionnaire to access frequency of meat food intake. The total of 1905 participants was available to data analysis in this study. Multiple regression models controlling for confounding factors to include frequency of meat food intake variable were performed to investigate the relationships for OP. RESULTS: Positive correlations between frequency of meat food intake and T-score were reported (beta = 0.12, P value < 0.001). Multiple regression analysis indicated that the frequency of meat food intake was significantly associated with OP (P < 0.1 for model 1 and model 2). The postmenopausal women with high frequency of meat food intake had a lower prevalence of OP. CONCLUSION: The findings indicated that frequency of meat food intake was independently and significantly associated with OP. The prevalence of OP was less frequent in Chinese postmenopausal women preferring meat food habits. PMID- 26885046 TI - Microsatellite instability of gastric cancer and precancerous lesions. AB - OBJECTIVE: To investigate whether microsatellite instability (MSI) of gastric cancer and precancerous lesions were existed and its effect. METHODS: Laser microdissection was used. Gastric, intestinal metaplasia, dysplasia and normal mucosa were collected respectively. Five microsatellite loci were selected and MSI was detected by denaturing high-performance liquid chromatography. RESULTS: In the five microsatellite loci REF-positive phenotype, intestinal metaplasia MSI was 20.7%. Dysplasia MSI was 22.4%. Gastric MSI was 47.9%, and there was no MSI in normal gastric mucosa. CONCLUSION: MSI gradually increased from precancerous lesions to gastric cancer. The early detection of MSI may be a potential early warning indicator for early diagnosis of gastric cancer. PMID- 26885047 TI - Genetic association between hOGG1 C8069G polymorphism and colorectal cancer risk. AB - BACKGROUND: hOGG1 C8069G polymorphism has been extensively investigated in single studies as well as meta-analyses in terms of the association with colorectal cancer (CRC). But the results remain contradictory. This study was undertaken to comprehensively evaluate the association of the commonly studied hOGG1 C8069G polymorphism and the susceptibility to CRC. METHODS: By searching the electronic databases of PubMed, Embase, and Web of science, 16 available publications consisting of 4,866 cases and 7,363 controls were finally included in our meta analysis. Stratified analyses by ethnicity and source of control were also carried out to further assess the association between hOGG1 C8069G polymorphism and CRC risk. RESULTS: hOGG1 C8069G polymorphism was not observed to have statistical significance with the susceptibility to CRC (ORCC vs. GG = 0.97, 95% CI = 0.91-1.05; P = 0.995; ORCC + CG vs. GG = 0.98, 95% CI = 0.93-1.04; P = 0.993; ORCC vs. CG + GG = 0.96, 95% CI = 0.90-1.02; P = 0.339; ORallele C vs. allele G = 0.98, 95% CI = 0.94-1.02; P = 0.912; ORCG vs. GG = 0.95, 95% CI = 0.88 1.03; P = 0.526). Similarly, no association was found in the subgroup analysis by ethnicity or the source of control. CONCLUSIONS: The results of our meta-analysis did not demonstrate any evidence for significant association between hOGG1 C8069G polymorphism and CRC risk. Future large-scale studies are expected to be conducted to further confirm our findings. PMID- 26885048 TI - Hand-assisted laparoscopic versus open radical resection of gastric remnant cancer: a clinical comparison. AB - OBJECTIVE: To compare the perioperative clinical data between hand-assisted laparoscopic and open radical resection of gastric remnant cancer, and analyze the feasibility and advantages of hand-assisted laparoscopic resection of gastric remnant cancer. METHODS: The clinical data of 18 patients with gastric remnant cancer who underwent hand-assisted laparoscopic (n=9) or open surgery (n=9) were retrospectively analyzed to compare the perioperative outcomes and recovery between December 2007 and October 2014. RESULTS: All 18 patients underwent surgery without post-operative complications. In the hand-assisted laparoscopy group, none required conversion to open surgery, and no intraoperative auxiliary injury occurred. The incision length was (8.78+/-0.62) cm in the hand-assisted laparoscopy group, and (14.06+/-0.81) cm in the open surgery group (t=15.565, P=0.000). The duration of the operation averaged (221.11+/-19.48) min in the hand assisted laparoscopy group, and (212.89+/-14.30) min in the open surgery group (t=-1.021, P=0.323). The intraoperative blood loss was (105.56+/-35.04) ml in the hand-assisted laparoscopy group, and (147.78+/-41.92) ml in the open surgery group (t=2.319, P=0.034). The number of lymph nodes scavenged was (16.22+/-2.99) and 16.67+/-3.28 in the hand-assisted laparoscopy group and in the open surgery group, respectively (t=-.300, P=0.768). The postoperative time to passage of gas by anus was (68.67+/-10.00) hr in the hand-assisted laparoscopy group, and (79.78+/-9.16) hr in the open surgery group (t=2.458, P=0.026). Mild postoperative hemorrhage occurred at the anastomotic site in one patient in each surgery group. These complications resolved after treatment. And no serious perioperative complications, such as anastomotic site fistula, massive hemorrhage in the peritoneal cavity or digestive tract or death occurred in either group. CONCLUSIONS: Hand-assisted laparoscopic radical resection of gastric remnant cancer is feasible, is of comparable efficacy to open surgery, and offers several advantages including small incisions, mild intraoperative hemorrhage, rapid postoperative recovery, and few postoperative complications. PMID- 26885049 TI - Gemcitabine plus S-1 versus cetuximab as a third-line therapy in metastatic colorectal cancer: an observational trial. AB - BACKGROUND AND AIM: After failure of oxaliplatin, irinotecan, and 5-fluorouracil (5-FU), there is no effective and low-cost therapy for metastatic colorectal cancer (mCRC). The purpose of this study was to assess the efficacy and safety of gemcitabine plus S-1 (GS) versus cetuximab as a third-line chemotherapy for mCRC patients. METHODS: Patients with previous failure of oxaliplatin, 5-FU, and irinotecan chemotherapy were included. The patients received GS or cetuximab until disease progression or intolerable toxicity occurred. The regimen that was selected by the patient depended on their economic ability. RESULTS: In all, 38 patients were enrolled between October 2009 and October 2012, and the patients were divided into 2 groups of 19 patients each. The median overall survival (OS) was 10 months for the GS group and 6.9 months for the cetuximab group (P = 0.047). The median progression-free survival (PFS) was 79 days and 78 days (P = 0.344), respectively. The disease control rate (DCR) was 42.11% and 47.37%, respectively (P = 0.985). The overall response rate was 0% and 10.52%, respectively (P = 0.169). Adverse events related to chemotherapy were mild to moderate. Only grade 3-4 neutropenia was found in the GS group at a rate of 21.1%. In the cetuximab group, the rash incidence rate was 89.6%, with 1 patient reaching grade 3. CONCLUSIONS: GS has benefits in OS compared with cetuximab, and is a promising and safe regimen as a third-line chemotherapy for oxaliplatin- and irinotecan-refractory mCRC with good performance status for mCRC patients. PMID- 26885051 TI - Functional exercise in combination with auricular plaster therapy is more conducive to rehabilitation of menopausal women patients with anxiety disorder. AB - OBJECTIVE: Observe the effect of functional exercise in combination with auricular plaster therapy on menopausal women patients with anxiety disorder. METHOD: Select 45 menopausal women patients with anxiety disorder and then adopt random digital table to divide them into a functional exercise group, an auricular plaster therapy group and a combination group. Each group consists of 15 patients. The patients in the functional exercise group do yoga exercise twice a day; those in the auricular plaster therapy group are provided with the auricular plaster therapy twice a day; those in the combination group do yoga exercise and then they are provided with the auricular plaster therapy twice a day. Before the treatment and after 12 weeks' treatment, respectively detect and compare the selected patients in the three groups in respect HAMA score, physical function score and mental function score; And the cured patients are followed up for 3 months to compare recurrence rate of each group. RESULTS: After 12 weeks' treatment, HAMA score, physical function score and mental function score of the combination group are obviously better than those of another two groups (P<0.05); Of the cure rate and the recurrence rate within 3 months, the cure rate of the combination group is higher and the recurrence rate is low. CONCLUSION: Through the functional rehabilitation exercise in combination with the auricular plaster, the combined curative effect is obviously better than that of single treatment and the clinical recurrence rate is significantly lower than that of single treatment. It shows that the combined treatment method presents obvious synergistic effect and the synergistic treatment is more beneficial to improve the curative effect. PMID- 26885050 TI - Effect of dexmedetomidine on myocardial ischemia-reperfusion injury. AB - Cardiopulmonary bypass (CPB) is associated with a marked systemic inflammatory response. Although dexmedetomidine (Dex) is routinely used in cardiac surgery, the effect in reducing the inflammatory response in coronary artery bypass graft surgery (CABG) with CPB remains unclear. In this study, Dex was administered at a loading dose of 0.5 MUg/kg for 10 min, followed by a continuous infusion of 0.5 MUg/kg per hour until the completion of CABG with CPB. The levels of inflammatory cytokines in the serum, including tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, IL-8 and IL-10, were measured to explore the inflammatory regulating function of Dex. In addition, troponin-I (cTnI) and creatine kinase (CK-MB) levels were studied to explore the myocardial protection provided by Dex. In this study, we showed Dex inhibited the increase in cTnI and CK-MB, attenuated the production of pro-inflammatory cytokines TNF-alpha, IL-6 and IL-8, and promoted anti-inflammatory cytokine IL-10 production. These findings demonstrate that Dex regulates anti-inflammatory as well as myocardial protection potential in CABG with CPB. PMID- 26885052 TI - Metabolomics analysis in rats after administration of Datura stramonium. AB - This study aimed to evaluate the effect of Datura stramonium on rats by examining the differences in urine and serum metabolites between Datura stramonium groups and control group. SIMCA-P+12.0.1.0 software was used for partial least-squares discriminant analysis (PLS-DA) to screen for the differential metabolites. Fifteen metabolites in urine including malonic acid, pentanedioic acid, D-xylose, D-ribose, xylulose, azelaic acid, threitol, glycine, butanoic acid, D-mannose, D gluconic acid, galactonic acid, myo-inositol, octadecanoic acid, pseudouridine and ten metabolites in serum including alanine, butanedioic acid, L-methionine, propanedioic acid, hexadecanoic acid, D-fructose, tetradecanoic acid, D-glucose, D-galactose, oleic acid were selected as the characteristic metabolites. The PLS DA scores plot indicated that serum and urine metabolites have a variety of changes among low dose group, high dose group and control group. These metabolites were related with amino metabolism, lipid metabolism and energy metabolism. The result reflected the relationship between metabolites in rat fluid and Datura stramonium spectra. Potential differences in metabolites and metabolic pathway analysis showed that the establishment of urine and serum metabolomics methods for further evaluating drug has great significance. PMID- 26885053 TI - Efficacy of transvaginal debridement and repair surgery for cesarean scar pregnancy: a cohort study compared with uterine artery embolism. AB - OBJECTIVE: Compared with uterine artery embolism (UAE), we aimed to investigate the efficacy and safety of transvaginal debridement and repair surgery (TDRS) and analyze the association between postoperative recovery and individual related factors. METHODS: A total of 128 patients diagnosed with cesarean scar pregnancy (CSP) from January 2006 to June 2014 were divided into 2 groups. Group A: 38 cases were treated with UAE. Group B: 90 cases were treated with TDRS, of whom 41 received preoperative chemotherapy. RESULTS: The failure rate in Group A was 5.3% (2/38) and the 2 cases of secondary vaginal hemorrhage after UAE were cured by hysterectomy and TDRS respectively. All patients were successfully treated in Group B and the postoperative outcomes of the patients who received preoperative chemotherapy showed no statistically differences compared with those who didn't. The hospital stays, serumbeta-hCG and menstruation recovery in Group B were significantly shorter than those in Group A (P<0.001). In Group B, there was no significant correlation between serumbeta-hCG recovery, menstruation recovery and individual related factors including serumbeta-hCG, gestational age and maximum diameter of gestational sac at diagnosis. CONCLUSION: Compared with UAE, TDRS is safer, more effective and with a rapider recovery. As an alternative therapeutic option, its prognosis isn't associated with some individual related factors. Furthermore, preoperative chemotherapy is unnecessary. PMID- 26885054 TI - A cross-sectional study to evaluate the associations between hypertension and osteoporosis in Chinese postmenopausal women. AB - BACKGROUND: This relationship between hypertension (HTN) and osteoporosis (OP) is not well documented among the population in China. The study sought to study the relationship between HTN and OP in Chinese postmenopausal women. METHODS: This cross-sectional study involved 1878 Chinese postmenopausal women with an average age of 62.38 years. OP was diagnosed by standardized quantitative ultrasound at the calcaneus and HTN was defined by blood pressure data and/or the use of antihypertensive medication. The relationship for OP and HTN were calculated using univariate and multivariate regression analyses. RESULTS: The prevalence of OP was 28.17% in the postmenopausal women, and there was a significant difference in the prevalence of OP between the two groups according to HTN (P value = 0.003). Univariate analysis demonstrates a positive correlation between HTN and OP. After adjustment for relevant potential confounding factors, multivariate logistic regression analyses detected significant associations between HTN and OP (P value = 0.096). In participants with HTN, the OR for OP was 1.209 (95% CI: 0.967-1.513). CONCLUSION: The prevalence of OP was more frequent in Chinese postmenopausal women with HTN, and HTN was independently and significantly associated with OP. PMID- 26885055 TI - Growth differentiation factor-15 (GDF-15), novel biomarker for assessing atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease. AB - OBJECTIVE: Growth differentiation factor-15 (GDF-15) has been identified as a strong biomarker of cardiovascular diseases; however, no evidence are available concerning the relationship of GDF-15 and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD). METHODS: Twenty patients with rheumatic heart disease were divided into two groups, 10 cases with AF and 10 cases with sinus rhythm (SR). Clinical data and blood samples were collected; left atrial appendage was taken by the surgeon in the process of valve replacement. Masson stained sections and mRNA levels of cardiac fibrosis biomarkers were used to determine the level of cardiac fibrosis, the expression level of GDF-15 was evaluated via immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). RESULTS: Compared with SR group, more collagen deposited in the atrial tissue of AF group. The distribution of GDF-15 in the AF group was significantly higher than SR group (P<0.05). In addition, plasma GDF-15 level and mRNA level of GDF-15 in atrial tissue of AF showed the same trend as the result of immunohistochemistry. After linear correlation analysis, the expression level of GDF-15 was found to be positively related to the degree of cardiac fibrosis. CONCLUSION: GDF-15 might involve in the development and maintenance of atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease, and GDF-15 could be used as a novel biomarker to evaluate myocardial fibrosis in the future. PMID- 26885056 TI - Variable lung protective mechanical ventilation decreases incidence of postoperative delirium and cognitive dysfunction during open abdominal surgery. AB - BACKGROUND: Postoperative cognitive dysfunction (POCD) is a subtle impairment of cognitive abilities and can manifest on different neuropsychological features in the early postoperative period. It has been proved that the use of mechanical ventilation (MV) increased the development of delirium and POCD. However, the impact of variable and conventional lung protective mechanical ventilation on the incidence of POCD still remains unknown, which was the aim of this study. METHODS: 162 patients scheduled to undergo elective gastrointestinal tumor resection via laparotomy in Ningbo No. 2 hospital with expected duration >2 h from June, 2013 to June, 2015 were enrolled in this study. Patients included were divided into two groups according to the scheme of lung protective MV, variable ventilation group (VV group, n=79) and conventional ventilation group (CV group, n=83) by randomization performed by random block randomization. The plasma levels of inflammatory cytokines, characteristics of the surgical procedure, incidence of delirium and POCD were collected and compared. RESULTS: Postoperative delirium was detected in 36 of 162 patients (22.2%) and 12 patients of these (16.5%) belonged to the VV group while 24 patients (28.9%) were in the CV group (P=0.036). POCD on the seventh postoperative day in CV group (26/83, 31.3%) was increased in comparison with the VV group (14/79, 17.7%) with significant statistical difference (P=0.045). The levels of inflammatory cytokines were all significantly higher in CV group than those in VV group on the 1st postoperative day (P<0.05). On 7th postoperative day, the levels of IL-6 and TNF-alpha in CV group remained much higher compared with VV group (P<0.05). CONCLUSIONS: Variable vs conventional lung protective MV decreased the incidence of postoperative delirium and POCD by reducing the systemic proinflammatory response. PMID- 26885057 TI - The independent association of platelet parameters with overall survival in pancreatic adenocarcinoma receiving intensity-modulated radiation therapy. AB - BACKGROUND: Platelets are involved in multiple links of the process of thrombus formation and development. The aim of this study is to investigate the impact of pretreatment platelet parameters, such as plateletcrit (PCT), platelet mean distribution width (MDW), and mean platelet volume (MPV) in a cohort of patients with locally advanced pancreatic adenocarcinoma treated with a combination of chemotherapy and radiation therapy. METHODS: A retrospective analysis was conducted of 163 locally advanced unresectable consecutive pancreatic adenocarcinoma patients who received chemoradiotherapy in Zhejiang cancer hospital from January 2009 to December 2011. The effects of platelet parameters on overall survival (OS) were assessed using Kaplan-Meier analysis. Independent prognostic factors were identified in the multivariate Cox analysis. RESULTS: The median of the PC, PCT, MDW, MPV and CRP were 175*10(9), 20.0%, 14.0%, 10.8 fl and 7.0 mg/L, respectively. MDW was positively correlated with PC (r=0.156, P=0.047) and CRP (r=0.591, P<0.001). The median survival time of high MDW group was significantly worse than that of low MDW group (14.0 m Vs 11.0 m, P=0.008). Patients with high PCT were found to have shorter overall survival time (15.0 m Vs 11.0 m, P=0.018). Multivariate analysis indicated that MDW and N stage were two independent prognostic factors for overall survival (P<0.05). Patients with higher MDW had a 1.48-fold increased risk of death compared to those with low MDW. CONCLUSIONS: MDW is an independent negative prognostic factor for overall survival in pancreatic adenocarcinoma patients. PMID- 26885059 TI - Expression and clinical significance of Tiam1 gene in esophageal carcinoma. AB - OBJECTIVE: To investigate the relationship between Tiam1 gene expression and the invasion and metastasis of esophageal cancer. METHODS: By RT-PCR technique, Tiam1 mRNA expression levels in 49 cases of esophageal cancer tissues and normal esophageal tissues were detected. RESULTS: Average Tiam1 mRNA expression level in 49 cases of esophageal cancer tissues (1.83 +/- 0.73) was significantly higher than that in normal esophageal tissues (0.87 +/- 0.45) (P < 0.01); High Tiam1 mRNA expression rate in esophageal cancer tissues was positively correlated with clinical stage and T stage; Tiam1 mRNA expression rate was 59.38% (19/32) in patients with lymph node metastasis, and in patients without lymph node metastasis it was 23.53% (4/17), with statistically significant differences (P < 0.05). CONCLUSION: Tiam1 gene expression in esophageal cancer tissues was significantly higher than that in normal esophageal tissues, and its overexpression was positively correlated with invasion and metastasis of esophageal cancer. PMID- 26885058 TI - The expression of AEG-1 and Cyclin D1 in human bladder urothelial carcinoma and their clinicopathological significance. AB - OBJECTIVE: Astrocyte elevated gene-1 (AEG-1) and Cyclin D1 is associated with tumorigenesis and progression. The aim of this study is to investigate the expression of AEG-1 and Cyclin D1 in human bladder urothelial carcinoma (BUC) and explore their clinical and pathological significance. METHODS: The expression of AEG-1 and Cyclin D1 protein were detected in 85 cases of human BUC and 16 cases of tumor-adjacent tissues by the immunohistochemical method. RESULTS: The positive expression level of AEG-1 was 61.2% in human BUC which was higher than that in tumor-adjacent tissues (18.8%), P=0.002. The high expression of AEG-1 protein was correlated with the recurrence group (P=0.004). The positive rate of AEG-1 protein in superficial carcinoma group was lower than that of invasive cancer group (P=0.014). The positive expression level of Cyclin D1 was 56.5% in BUC, which was higher than that in tumor-adjacent tissues (12.5%). P=0.001. The high expression of Cyclin D1 protein was correlated with the recurrence group (P=0.024). The positive rate of Cyclin D1 protein in low grade group was lower than that of high grade group (P=0.001). The positive rate of Cyclin D1 protein in superficial carcinoma group was lower than that of invasive carcinoma group, (P=0.012). AEG-1 protein was positively correlated with Cyclin D1 protein (r=0.567, P<0.001). The log-rank test statistical analysis suggested that patients with higher AEG-1 or Cyclin D1 expression had shorter overall survival time, while patients with lower AEG-1 or Cyclin D1 expression had better survival. CONCLUSION: Overexpression of AEG-1 and Cyclin D1 are markedly correlated with TNM stage and recurrence of BUC. Cyclin D1 are markedly correlated with grade of BUC. Detection of AEG-1 and Cyclin D1 may be helpful to evaluate prognosis and infiltrative capability of BUC. PMID- 26885060 TI - The optimum dose of intranasal remifentanil for laryngeal mask airway insertion during sevoflurane induction in children: a randomized controlled trial. AB - OBJECTIVE: The purpose of this study was to determine the optimum dose of intranasal remifentanil required to produce satisfactory laryngeal mask airway (LMA) insertion conditions during inhalation induction of anesthesia using 5% sevoflurane in children. METHODS: Seven-five American Society of Anesthesiologists physical status (ASA) I subjects, aged 2-5 years, scheduled for minor elective surgery were randomly allocated to receive one of five doses of intranasal remifentanil (nil, 0.25, 0.5, 0.75 and 1.0 MUg.kg(-1)) during 5% sevoflurane induction. Laryngeal mask insertion was attempted 120 s after intranasal remifentanil administration and the response of subjects was classified as either 'Failure' or 'Success'. "Success" was defined as a relaxed mandible without coughing, gapping, swallowing, laryngospasm or gross purposeful movement. Secondary outcomes included the duration of apnea, hemodynamic changes and complications. RESULTS: For each groups (nil, 0.25, 0.5, 0.75 or 1.0 MUg.kg( 1) remifentanil), the incidence of satisfactory LMA insertion conditions was 0, 33.3%, 60%, 86.7% and 100% respectively. None of subjects suffered from any serious complications such as laryngospasm,or hypotension and bradycardia. CONCLUSION: The ED50 and ED95 of intranasal remifentanil for successful LMA insertion in children were estimated to be 0.36 and 0.998 MUg.kg(-1) during 5% sevoflurane inhalation induction for 3 min. PMID- 26885062 TI - Imaging study on the optic canal using sixty four-slice spiral computed tomography. AB - BACKGROUND: Rapid advances in multislice computed tomography (MSCT) technology facilitate accurate clinical imaging. The newly developed 64-slice CT increases temporal and spatial resolution efficiently. PURPOSE: The purpose of this study is to evaluate the application of 64 slice spiral computed tomography (CT) on the imaging of the normal optics canal. METHODS AND MATERIALS: 100 healthy adults were investigated using 64 slice spiral CT. The optics canal was scanned, reconstructed and examined. RESULTS: Among the four walls of the optic canal, the medial wall is the longest one. The upper wall and outer wall are inferior to the medial wall while the inferior wall is the shortest one. All the data accomplished by the 64 slice CT was consistent with the results of previous reports using other methods. CONCLUSION: The results suggested that the 64 slice spiral CT could be a valuable and accurate method for measuring the length of optics canal walls. PMID- 26885061 TI - MicroRNA-155 expression as a prognostic factor in patients with gallbladder carcinoma after surgical resection. AB - BACKGROUND: MicroRNA-155 (miR-155) is over-expressed in both hematopoietic malignancies and solid tumors. In the present study, we investigated the clinical significance of miR-155 in gallbladder carcinoma among Chinese population. METHODS: Tissue specimens were collected from 133 patients who had undergone surgical resection at Shandong Provincial Hospital, Shandong University between May 2008 and April 2014. We profiled miR- 155 expression in the gallbladder carcinoma tissues and normal gallbladder tissues by qRT-PCR. The Kaplan-Meier method was used to analyze the 5-year survival rate. RESULTS: The expression levels of miR-155 were significantly higher in gallbladder carcinoma tissues than that in normal gallbladder tissues (P<0.001). High miR-155 expression was significantly associated with TNM stage (P=0.003), lymph node status (P=0.042), liver metastasis (P=0.010), and differentiated degree (P<0.001). We found that gallbladder carcinoma patients with high miR-155 expression level had distinctly shorter overall survival than patients with low miR-155 expression level (P=0.03). Multivariate analysis revealed that miR-155 expression level was independent prognostic factors for overall survival (HR=2.394, 95% CI: 1.568 10.034; P=0.009). CONCLUSION: High miR-155 expression is a prognostic indicator for poor prognosis of patients with gallbladder carcinoma among Chinese population. PMID- 26885063 TI - From angiomyolipoma to malignant epithelioid angiomyolipoma of the kidney, a case report with a history of eight years. AB - Epithelioid angiomyolipoma (EAML) is a rare subtype of angiomyolipoma (AML) with potential has malign tendency. UP to now, the biological association between EMAL and typical AML is not well known. In the present study, we reported a case of EMAL arose in AML seven years post AML operation. A 34-year-old man with bilateral kidney AML was operated with an open cytoreductive surgery of both sides. After seven years, the left nephrectomy was performed due to a new neoplasm was found in the left kidney. The pathology diagnosis and inmmunohistochemical staining suggested the new neoplasm was EAML. Finally the patient developed metastases to liver and retroperitoneum and died 19 months post the last operation. After reviewing the history of the patient, we thought that the EAML might be developed from a little amount of EMAL accompany with AML in the small lesson that was missed by the CT scan. The results revealed that a carefully screening for the epithelioid cells in the typical AML specimen should be made to avoid missing the important EAML. PMID- 26885064 TI - CXCR7 expression in nasopharyngeal carcinoma tissues correlates with disease severity. AB - The chemokine CXCL12 and its receptors, CXCR4 and CXCR7, are important contributors to the pathogenesis of multiple types of tumors. CXCL12/CXCR4 was previously demonstrated to be upregulated in nasopharyngeal carcinoma (NPC) tissues, but the status of CXCR7 in NPC remains unknown. Here, 62 nasopharyngeal carcinoma specimens were obtained from patients who received rhinitis biopsy in our hospital in 2012 and 2013. Another 30 samples were collected from patients with nasopharyngitis who did not have NPC, to serve as a control group. Expression of CXCR7 protein and mRNA in NPC and normal tissues was detected by immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. CXCR7 protein was detected in just 7.1% (2/30) of normal nasopharyngeal samples, but 61.3% (38/62) of tumor tissues (P<0.05). The staining patterns (proportion of stained cells/sample as well as staining intensity) were correlated with lymph node metastasis, TNM staging, and disease severity (P<0.01). Thus, CXCR7 may promote disease progression in nasopharyngeal carcinoma, and may be useful as a predictor of metastasis and prognosis. PMID- 26885065 TI - Penis keratoacanthoma transforming into squamous cell carcinoma: a rare case. AB - Keratoacanthoma is variously regarded as a benign epithelial tumor, characterized by a rapid-growing and solitary flesh-colored nodule with a central keratin plug on the sun-exposed skin. Under certain circumstances, it can transform into squamous cell carcinoma. In this paper, we present a case of a 50-year-old man with a 2.5 * 3 * 2.2 cm mass on his penis stub-end. The patient was treat with a partial penectomy after further expert discussions and histopathology the lesion demonstrated penis keratoacanthoma. He received a partial penectomy again and the pathological result revealed squamous cell carcinoma this time. This case indicates that undergoing a partial penectomy on initial diagnosis of a penile tumor secondary to penile keratoacanthoma should be considered because of its high malignant potency. To our best knowledge, this is the first study to describe the malignant conversion of penis keratoacanthoma. PMID- 26885066 TI - Cost of general anesthesia during radical gastrectomy using different specifications of propofol: cost-minimization analyses. AB - BACKGROUND: Recently, the economic cost of anesthesiahas attracted attention. To compare the costs of three methods of general anesthesia (GA), a retrospective 1 year study was designed for patients undergoing radical resection for gastric carcinoma. METHODS: A total of 398 patients were originally included in the study. Subjects were divided into three groups according to the mode of anesthesia: balanced anesthesia (BAL; n=258), total intravenous anesthesia (TIVA; n=36), and inhalational anesthesia (INH; n=104). RESULTS: When patients were undergoing elective radical resection for gastric carcinoma, the duration of anesthesia, age, duration of surgery, and postoperative analgesia were positively correlated with the total cost of anesthesia (including wastage of propofol 200 mg:20 mL). Duration of anesthesia and postoperative analgesia were positively correlated with the total cost of anesthesia (including wastage of propofol 500 mg:50 mL). However, the anesthesia group was negatively correlated with the total cost of anesthesia (including drug wastage). When propofol 500 mg:50 mL was used, the total cost of anesthesia and total cost of anesthesia per hour in the BAL group was higher than in the INH group. However, when excluding drug wastage (propofol 200 mg:20 mL), the BAL group was more expensive than the other two groups. CONCLUSION: Use of propofol 200 mg:20 mL as a GA would save money. PMID- 26885067 TI - Risk factors, management, and prognosis for liver abscess after radical resection of hilar cholangiocarcinoma. AB - OBJECTIVES: Pyogenic liver abscess (PLA) is a rare but potentially lethal infectious complication after radical surgical resection of hilar cholangiocarcinoma (HC), this study is aimed to identify the risk factors, management and prognosis of PLA after curative surgical resection of HC. METHODS: Between January 2003 and October 2013, 95 patients who underwent surgical resection of HC at a tertiary center were included in this study. The risk factors pertaining to PLA formation were identified by exact logistic regression. RESULTS: PLA developed in 8 of 95 patients. The median duration of PLA formation following surgical procedure was 145 days (range, 16-295 days) and the most commonly isolated microorganism was Escherichia coli (4/8). Though most patients who developed PLA after surgery were successfully managed with antibiotics and invasive therapy, the overall survival was statistically poorer than those without PLA formation (median, 16.9 vs. 34.2 months, P=0.048). Univariate analysis revealed that coexisting biliary disorders (37.5% vs. 8.0%, P=0.036), vascular reconstruction (37.5% vs. 9.2%, P=0.041) and margin status (62.5% vs. 21.8%, P=0.023) were associated with PLA formation, whereas only vascular reconstruction (odds ratio (OR), 10.31; 95% confidence interval (CI), 1.03 142.73; P=0.047) and margin status (OR, 8.45; 95% CI, 1.13-109.38; P=0.035) were identified as independent risk factors by multivariate analysis. CONCLUSIONS: Intraoperative vascular reconstruction and positive margin status pose greater risks for PLA formation after radical resection of HC. For patients with high risk factors, careful follow-up is needed for early detection and management of this infrequent complication. PMID- 26885068 TI - Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats. AB - This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-alpha, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-alpha levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-alpha levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-alpha effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID- 26885069 TI - The relation between erectile dysfunction and extent of coronary artery disease in the patients with stable coronary artery disease. AB - INTRODUCTION: Erectile dysfunction (ED) and coronary artery disease (CAD) are closely related as a result of endothelial dysfunction leading to the restriction of blood flow. ED is a potential independent risk factor of CAD. We investigated the prevalence and severity of ED, the extent of CAD and the time interval between the symptoms of ED and CAD in the stable coronary artery patients. MATERIALS AND METHODS: 161 patients applied coronary angiography were divided into two groups according to SYNTAX score as group 1 (n=81) SYNTAX score <=22, and group 2 (n=80) SYNTAX score >22. The prevalence and severity of ED was determined by using The International Index of Erectile Function (IIEF). RESULTS: The prevalence of ED was 43.2% in group 1 and 61.3% in group 2 (P=0.022). The score of IIEF was 23.1 (15-29) in group 1, 19.3 (6-29) in group 2; there was a significant difference (P=0.000). In the multivariate logistic regression analysis carried out in order to determine the independent predictors on Syntax score, it was found that LDL (odds ratio: 1.032, 95% confidence interval: 1.009 1.055, P=0.007) and IIEF score (odds ratio: 0.825, 95% confidence interval: 0.733 0.928, P=0.001) were the independent predictors. The time between the symptoms of ED and CAD 30.1 +/- 4.8 months in group 1, and 40.5 +/- 4.3 months in group 2 (P=0.000). CONCLUSION: The severity of ED is an independent factor predicting the extent of CAD. The early detection of ED enables to make a cardiovascular evaluation. Therefore, taking the cardiovascular risk factors under an aggressive treatment may contribute to prevent the cardiovascular cases which may develop in the future. PMID- 26885070 TI - Discrepant clinicopathologic characteristics and HE4 performance in type I and type II epithelial ovarian cancer. AB - Recent studies have demonstrated that epithelial ovarian cancer (EOC) are factual several different diseases. A two-tier system divides EOC into type I and type II EOC. HE4 has been used as a complementary biomarker for diagnosing EOC. This study aimed to evaluate the different clinicopathologic characteristics and HE4 expression levels in types I and II EOCs. This retrospective study included 127 EOC patients. Data related to patient demographics, cancer stages, grades, histology, operation procedures, residual disease, adjuvant chemotherapy, recurrence, and survival were collected. A total of 134 ovarian carcinoma tissue specimens and 40 matching borderline ovarian tumor specimens were chosen from the pathology department archives. Immunohistochemistry was used to assess HE4 expression in EOC and borderline ovarian tumor tissue specimens. Of the 127 patients, there were 42 type I EOC patients (7 low grade serous carcinomas, 8 mucinous carcinomas, 12 low grade endometrioid carcinomas and 15 clear cell carcinomas) and 85 type II EOC patients (83 high grade serous carcinomas and 2 high grade endometrioid carcinomas). The median followed--up time was 18.3 months. There were significant differences between the two types of EOC in terms of the menopausal state, FIGO stage and pathological differentiation, but there were no differences in the residual tumor and chemotherapy treatment. In type I EOC, the median follow--up time was 31 months and the median progression--free survival was 72 months (95% CI: 40.34-103.66). There were 15 (35.7%) relapsed or progressive patients. In type II EOC, the median follow-up time was 17 months (0 60 m), and the median progression--free survival was 27 months (95% CI: 17.83 36.17). There were 47 (55.3%) relapsed or progressive patients. There was a significant difference between the two types of EOCs in terms of progression- free survival (P<0.001). Among the 44 type I specimens, 25 demonstrated positive expression of HE4 (56.8%). In contrast, 78 (86.7%) type II EOC demonstrated positive expression levels. There was a significant difference between type I and type II EOCs in terms of HE4 expression. Additionally, there was a significant difference between high grade serous carcinoma and borderline serous tumor, but no difference was observed between low grade serous carcinoma and borderline serous tumor or other types of EOC and corresponding borderline tumors. The different clinicopathologic characteristics between type I and type II EOC indicate that the two--tier EOC system reasonable and reliable. HE4 would be a powerful biomarker to distinguish type II EOC from borderline tumors but it is less useful in type I EOC. Type I EOC is generated from the corresponding borderline tumor. PMID- 26885071 TI - The association and interaction analysis of hypertension and diabetes mellitus on diastolic heart failure in a high-risk population. AB - OBJECTIVE: The purpose of this study was to evaluate the extent to which hypertension (HT) interacts with diabetes mellitus (DM) to affect diastolic heart failure (DHF) in a high-risk population. METHODS: We conducted a hospital-based case-control study to investigate the relationship between HT or DM and DHF in 251 patients (case: 133 patients with DHF; control: 118 patients without DHF). Echocardiography was used to assess left ventricular (LV) diastolic function. The association between HT or DM and DHF was assessed by multivariate logistic regression (MLR) analysis controlling for confounders. The effect of the interaction between HT and DM on DHF was assessed in MLR models. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). RESULTS: The MLR analyses showed that HT and DM were independent predictors of DHF after adjustment for potential confounders (OR = 2.35-3.14, P<0.05 for all models). DHF was affected by the interaction between HT and DM (ORInt = 3.11-4.31, P Int<0.1, RETI = 2.13-2.69, AP = 0.38-0.49 and S = 4.11-6.80). CONCLUSION: The findings provide evidence that HT and DM are independent predictors of DHF and that both risk factors act synergistically to influence DHF in a Chinese high-risk population. PMID- 26885072 TI - Microendoscopy-assisted minimally invasive transforaminal lumbar interbody fusion for lumbar degenerative disease: short-term and medium-term outcomes. AB - OBJECTIVE: To evaluate short-term and medium-term outcomes of microendoscopy assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open TLIF for lumbar degenerative disease. METHODS: In this prospective, randomized control study, 50 cases received microendoscopy-assisted MIS-TLIF (MIS group), while another well-matched 50 cases accepted open TLIF (open group). Parameters between both groups, including surgical duration, intraoperative blood loss and radiologic exposure, postoperative analgesic usage and ambulatory time, visual analogue scale (VAS) for back and leg, functional scores, self-evaluation of surgical outcome (modified MacNab criteria), interbody fusion rate, adjacent segment degeneration (ASD) rate, as well as complication incidence were compared at 1 month and 24 months postoperatively. RESULTS: Intraoperative blood loss and postoperative analgesic usage were significantly reduced in MIS group (P<0.05). Patients undergoing microendoscopy-assisted MIS-TLIF were able to ambulate earlier postoperatively than those receiving open TLIF (P<0.05). However, it showed prolonged surgical duration and enhanced radiologic exposure in MIS group (P<0.05). At 1 month postoperatively, MIS group was associated with more improvement of VAS and functional scores compared with open group (P<0.05). While at 24 months postoperatively, both groups revealed similar VAS and functional scores (P>0.05). Excellent and perfect scale rating by modified MacNab criteria, interbody fusion rate, ASD rate and complication incidence between both groups were nearly the same (P>0.05). CONCLUSIONS: Microendoscopy-assisted MIS-TLIF owns advantages of less iatrogenic injury, decreased blood loss, reduced analgesic usage and earlier rehabilitation, while it has drawbacks of more surgical duration and radiologic exposure. It is superior than open TLIF in terms of short term clinical outcomes and has similar medium-term clinical outcomes. PMID- 26885074 TI - Cabbage compression early breast care on breast engorgement in primiparous women after cesarean birth: a controlled clinical trial. AB - This study aimed to compare the effects of cabbage compression early breast care (CCEBC) and early breast care (EBC) on breast pain, breast hardness with general nursing breast care (GNBC) in primiparous women after cesarean birth. Sixty participants were divided to three groups including CCEBC, EBC and GNBC. Each group was treated with its intervention respectively more than 10 minutes before breast feeding from day two to day four after delivery. The primary outcomes were breast pain and breast hardness. Both CCEBC and EBC showed significantly lower pain level than GNBC at day 4 after delivery. There are significant differences of breast hardness among three groups. CCEBC group showed significantly lower breast hardness compared with EBC and GNBC. Neither core body temperature nor breast skin temperature was significantly different among the three groups. In conclusion, CCEBC may effective in relieving breast pain and breast hardness compared with EBC alone and GNBC in primiparous women after a cesarean birth. PMID- 26885073 TI - Clinical significance of preoperative detection of serum p53 antibodies and BRAF(V600E) mutation in patients with papillary thyroid carcinoma. AB - The goal of the present study was to evaluate the clinical and diagnostic value of both serum p53-antibodies (Abs) and preoperative fine needle aspiration cytology (FNAC) for BRAF mutation in patients with papillary thyroid carcinoma (PTC). A total of 312 patients, including thyroid adenoma (85) and PTC (227) were enrolled in this study. Two types of enzyme-linked immunosorbent assays (ELISA), phage-ELISA and p53-ELISA, were used to measure serum p53-Ab levels. Sanger sequencing was used to determine BRAF gene mutation in FNA samples. Phage-ELISA was more efficient than conventional p53-ELISA in measuring serum p53-Abs in PTC patients. BRAF mutation analysis with FNAC significantly improved PTC diagnostic sensitivity from 80.18% to 93.83% (P=0.001) and accuracy from 82.31% to 92.37% (P=0.005). Bothp53-Abs and BRAF mutation were positively associated with lymphatic metastasis and advanced TNM stages. Particularly, serum p53-Abs positively associated with multifocality (P=0.02), while BRAF mutation associated with extrathyoidal extension (P=0.01). Furthermore, PTC patients with both elevated serum p53-Abs and BRAF mutation had a higher prevalence of extrathyoidal extension (P=0.003), lymphnode metastasis (P=0.00), multifocality (P=0.04), and advanced TNM stages (P=0.004). Our results indicate that serum p53-Abs alone might not be a reliable biomarker for PTC diagnosis, but the combined analysis of serum p53-Abs and BRAF mutation in FNAC may be useful for optimizing surgical treatment and prognostic prediction of unfavorable clinicopathologic outcomes. PMID- 26885075 TI - A tagging ALOX5AP polymorphism and risk of ischemic stroke in a northeastern Chinese Han population. AB - OBJECTIVE: 5-lipoxygenase-activating protein gene (ALOX5AP) has been recognized as a susceptibility gene for stroke. In this work, we explored the association of 6 ALOX5AP SNPs with cerebral infarction (CI) in a northeastern Chinese Han population, using a case-control design. METHODS: A group of patients with cerebral infarction were randomly chosen as case group in northeastern Chinese Han population. Another comparative group of individuals without stroke were chosen as the control group. By utilizing TaqMan probe based real-time fluorescent PCR and DNA sequencing method, this study focused on 6 SNPs of ALOX5AP gene and analyzed the association with the hereditary susceptibility of cerebral infarction. RESULTS: We found that, the rs9579646 G allele frequency was significantly associated with higher ischemic cerebral infarction. There was no significant difference of rs9551963, rs9315050, rs4769874, rs10507391 and rs4147064 genotype frequencies between the case and control group. Haplotype based association analysis of the block involving rs9579646 and rs10507391 revealed that the increased risk of stroke was significantly associated with haplotype GT and GA. CONCLUSION: These results suggested that the genetic variants in ALOX5AP might be related to the risk of stroke in northeastern Chinese Han population. The SNP rs9579646 may be a diagnostic index of cerebral infarction. PMID- 26885076 TI - Ischemic and hemorrhagic moyamoya disease in adults: CT findings. AB - OBJECTIVE: To investigate the findings of adult moyamoya disease (MD) of different types on plain CT, brain perfusion CT (CTP) and brain CT angiography (CTA). MATERIALS AND METHODS: A total of 48 patients with ischemic MD and hemorrhagic MD were recruited into present study, and findings were collected from plain CT, CTP and CTA. RESULTS: The incidence of watershed or cortex stroke in ischemic MD (55.6% and 38.9%) was higher than in hemorrhagic MD (0%). The incidence of ventricle or basal ganglia stroke in hemorrhagic MD (40.0%, 43.3%) was higher than in ischemic MD (0%, 5.6%). CTP showed hypoperfusion in 11 patients, hyperperfusion in 12 and normal perfusion in 25. Ischemic MD patients were more likely to present hypoperfusion (61.1%; normal perfusion: 22.2%; hyperperfusion: 16.7%). Hemorrhagic MD patients were more likely to present normal perfusion (70%; hyperperfusion: 30%; hypoperfusion: 0%). The incidence of grade II MD in ischemic MD (27.8%) was higher than in hemorrhagic MD (6.7%). The incidences of grade IV and V MD in hemorrhagic MD (33.3% and 16.7%) were higher than in ischemic MD (16.7% and 11.0%). CONCLUSION: Hemorrhagic MD is dominant in adults with MD and stroke of these patients mainly occurs at the intraventricular space and basal ganglia. Ischemic MD in adults is characterized by hypoperfusion and hemorrhagic MD by normal perfusion on CTP. MD in adults is usually classified as grade II, III or IV on CTA. PMID- 26885077 TI - Risk factors associated with splenic hilar lymph node metastasis in patients with advanced gastric cancer in northwest China. AB - There are plenty of risk factors associated with splenic hilar lymph node metastasis (SHLNM) in patients with advanced gastric cancer (AGC). Whereas, their main influencing factors have not reached a consensus yet. The aim of the study is to investigate the related clinicopathological factors influencing SHLNM in AGC. A retrospective study was performed to investigate 150 patients who underwent D2 curative partial or total gastrectomy for gastric carcinoma from January 2007 to November 2012. Clinicopathological factors were analyzed by univariate and multivariate analysis. A total of 10.7% (16/150) of the patients had SHLNM. The overall ratio of metastatic lymph node (positive lymph nodes/lymph nodes harvested) in the splenic hilum was 17.5% (38/217). Univariate analysis results showed SHLNM was related with depth of invasion, tumor grade, tumor size, tumor location and Bormann type, with significant difference (P<0.05); Multivariate analysis demonstrated that SHLNM was related with depth of invasion and tumor size, with significant difference (P<0.05). Consequently, depth of invasion, tumor grade, tumor size, tumor location and Bormann type were associated with SHLNM in AGC, meanwhile depth of invasion and tumor size are independent risk factors. Preoperative predicting risk factors of SHLNM greatly benefits making more rational surgical scheme of treating AGC. PMID- 26885078 TI - Effect of Radix Sophorae Flavescentis on activity of CYP450 isoforms in rats. AB - Kushen (Radix Sophorae Flavescentis) is the dried roots of Sophora Flavescens Ait, alkaloids and flavonoids are the main active constituents of Radix Sophorae Flavescentis. The influence of Radix Sophorae Flavescentis on the activities of CYP450 isoforms CYP2B6, CYP2C19, CYP1A2, CYP2C9, CYP3A4 and CYP2D6 were evaluated by cocktail method. The rats were randomly divided into Radix Sophorae Flavescentis group and control group. The Radix Sophorae Flavescentis group rats were given 5 g/kg Radix Sophorae Flavescentis decoction by intragastric administration. The six probe drugs (bupropion, omeprazole, phenacetin, tolbutamide, midazolam and metroprolol) were given to rats through intragastric administration, and the plasma concentration were determined by UPLC-MS/MS. The result of Radix Sophorae Flavescentis group compared to control group, there were statistical pharmacokinetics difference for omeprazole, phenacetin, tolbutamide and metroprolol. It indicated that the Radix Sophorae Flavescentis may induce the activities of CYP2D6, and inhibit of CYP2C19, CYP1A2 and CYP2C9 of rats. As other drugs are always used after Radix Sophorae Flavescentis, interactions between other drugs and Radix Sophorae Flavescentis undertake the risk of either diminished efficacy or adverse effects. This may give advising for reasonable drug use after Radix Sophorae Flavescentis. PMID- 26885079 TI - Concurrent gastrointestinal stromal tumor and digestive tract carcinoma: a single institution experience in China. AB - The aim of this study was to review the clinicopathological characteristics and survival outcomes of patients with concurrent gastrointestinal stromal tumor (GIST) and digestive tract carcinoma. Among 585 patients diagnosed with GIST from January 2005 to July 2014, 32 (5.5%) had synchronous digestive tract carcinoma, including 19 (59.4%) men and 13 (40.6%) women. The median age was 64 years (range, 43-84). GIST was located in the stomach (n=24), small intestine (n=6), duodenum (n=1) and retroperitoneum (n=1). GISTs were intra- or postoperatively discovered (n=28) or preoperatively identified (n=4). The tumor size was less than 10 mm (microGIST) in 23 (71.9%) GIST patients. The preoperatively identified GIST subgroup showed a significantly larger tumor size, more mitotic figures and a higher risk grade than the intra- or postoperatively identified GIST subgroup. Concurrent digestive tract carcinomas were most frequently located in the stomach (24 cases, 75%). The other involved sites were the esophagus (n=5), duodenum (n=2) and colon (n=1). With a median follow-up of 32 months (range, 9-80), 24 patients were alive without evidence of disease, 6 patients had died of carcinoma progression, 1 patient had died from an accident, and 1 patient experienced GIST metastasis to the liver. In summary, we discovered that 5.5% of GIST patients also developed a concurrent digestive tract carcinoma in a series of 585 GIST cases. The majority of GISTs are incidentally identified microGISTs. The concurrent carcinoma seems to have a greater unfavorable effect on prognosis than the GIST. However, for a GIST that is identified preoperatively with a high risk of progression, adjuvant therapy is warranted. PMID- 26885081 TI - Curative effect of Tai Chi exercise in combination with auricular plaster therapy on improving obesity patient with secondary hyperlipidemia. AB - OBJECTIVE: Observe the effect of Tai Chi in combination with auricular plaster therapy on treating obesity patient with secondary hyperlipidemia. METHOD: Select 45 patients who suffer from simple obesity and secondary hyperlipidemia and then adopt random digital table to divide them into a Tai Chi group, an auricular plaster therapy group and a combination group. Each group consists of 15 patients. The patients in Tai Chi group are trained with Tai Chi twice a day, while those in auricular plaster therapy are treated with auricular plaster therapy 3-5 times a day and those in the combination group are trained with Tai Chi and auricular plaster therapy twice a day. BMI, body fat percentage and blood lipid indexes are respectively detected for the selected patients in the three groups before treatment and after 180 days' treatment. RESULTS: After 180 days' treatment, BMI index and body fat percentage of Tai Chi group are significantly improved in comparison with those before treatment (P<0.05) and the blood lipid index also presents the improvement trend, but the overall effect is not obvious; body fat percentage and BMI index of the auricular plaster therapy group are not improved obviously in comparison with those before the treatment (P>0.05) but the blood lipid index is improved significantly (P<0.05); each index of the combination group is improved significantly compared with those before treatment (P<0.05). By comparing the improvement effect after treatment with that of the other two groups, P<0.05, the difference shows the statistical significance and the treatment effect is more obvious. CONCLUSION: As for the patient suffering from simple obesity and secondary hyperlipidemia, Tai Chi exercise in combination with auricular plaster therapy can show the obvious synergistic therapeutic effect and thus the combined curative effect is obviously superior to that of the single therapy method. PMID- 26885082 TI - Biological mechanisms of premature ovarian failure caused by psychological stress based on support vector regression. AB - Psychological stress has become a common and important cause of premature ovarian failure (POF). Therefore, it is very important to explore the mechanisms of POF resulting from psychological stress. Sixty SD rats were randomly divided into control and model groups. Biomolecules associated with POF (beta-EP, IL-1, NOS, NO, GnRH, CRH, FSH, LH, E2, P, ACTH, and CORT) were measured in the control and psychologically stressed rats. The regulation relationships of the biomolecules were explored in the psychologically stressed state using support vector regression (SVR). The values of beta-EP, IL-1, NOS, and GnRH in the hypothalamus decreased significantly, and the value of NO changed slightly, when the values of 3 biomolecules in the hypothalamic-pituitary-adrenal axis decreased. The values of E2 and P in the hypothalamic-pituitary-ovarian axis decreased significantly, while the values of FSH and LH changed slightly, when the values of the biomolecules in the hypothalamus decreased. The values of FSH and LH in the pituitary layer of the hypothalamic-pituitary-ovarian axis changed slightly when the values of E2 and P in the target gland layer of the hypothalamic-pituitary ovarian axis decreased. An Imbalance in the neuroendocrine-immune bimolecular network, particularly the failure of the feedback action of the target gland layer to pituitary layer in the pituitary-ovarian axis, is possibly one of the pathogenic mechanisms of POF. PMID- 26885083 TI - Change in pulmonary function in chronic obstructive pulmonary disease stage 0 patients. AB - This study aims to elucidate the change in pulmonary function in stage 0 COPD patients. A total of 48 stage 0 COPD patients and 46 healthy adults were included in the study. The status of their pulmonary function was determined by an impulse oscillometry (IOS) system, and the spirometric indexes such as forced vital capacity, maximum expiratory flow-volume (MEFV) curve, total respiratory impedance (Zrs) and respiratory resistance (Rrs) between the two groups were compared. Significant decreases in the values of forced expiratory flow (FEF) at both 75% and 50% of the vital capacity of the predicted value (EF75/pre and FEF50/pre) were detected in stage 0 COPD patients compared with those in the control (P < 0.05). Significant increases were found in the resonant frequency (Fres) (14.37+/-3.63 VS 11.26+/-2.61), total respiratory impedance (Z5) compared with the prediction (Z5/pre) (135.65+/-19.37 VS 104.69+/-20.64), total airway resistance at 5 Hz (R5) compared with prediction (R5/pre) (128.46+/-20.14 VS 100.60+/-20.98) and peripheral airway resistance (R5-R20) compared with prediction (R5-R20/pre) (282.34+/-192.83 VS 109.31+/-80.05) in the study group compared with those in the control(all P < 0.05). The reactance at 5 Hz (X5) ( 0.14+/-0.05 VS -0.08+/-0.05) in the stage 0 COPD group was markedly lower than that in the healthy group (P < 0.05). Disturbance in the small airway may be detected by the MEFV curve and IOS, and these indexes would be valuable in diagnosing stage 0 COPD. PMID- 26885080 TI - Dysregulation of hedgehog signaling pathway related components in the evolution of colonic carcinogenesis. AB - Previous studies report controversial role of Hedgehog (HH) signaling in the progression of colon cancer. This study aimed to investigate the expressions of smoothened (SMO) and downstream glioma-associated oncogene homology-1 (GLI1) in colon cancer, colonic adenoma and normal tissues. Colon cancer and normal tissue samples were collected from 49 patients with colon cancer while colonic adenoma tissue samples were obtained from 34 patients with colonic adenoma. Then the expressions of SMO and GLI1 were investigated using immunohistochemistry (IHC). For the detection of SMO and GLI1 expression, IHC staining results indicated that SMO was mainly expressed on the membrane while GLI1 was mainly expressed in the cytoplasm. The positive rates of SMO and GLI1 protein expressions were significantly increased in colon cancer tissue and colonic adenoma tissue when compared with normal colon tissue. In contrast, the significant difference was not found in the positive rates of SMO and GLI1 protein expressions between colon cancer tissue and colonic adenoma tissue. More importantly, it was found that SMO and GLI1 expressions possibly increased gradually from the normal colon to colonic adenoma to the colon cancer. Furthermore, no distinct correlations were detected between the expression levels of SMO and GLI1 and clinicopathological parameters, including age, gender, differentiation and Dukes stage. The present results provided some new information to the possible role of HH signaling in colon cancer progression. SMO and GLI1 maybe suggested asbiomarkers to identify colon cancerous, precancerous and normal tissues as well astherapeutic targets for colon cancer treatment. PMID- 26885084 TI - Genetic association of G-607C Located at wnt10b promoter with bi-sup type among Korean cerebral infarction patients. AB - Obesity is a disease threatening health and is known one of risk factors causing chronic disease. In Traditional Korean Medicine, bi-sup is casus of obesity. Wnt10b has been indicated as a potential regulator of adipogenesis in vivo and in vitro models of obesity. To analyze the distribution of wnt10b polymorphism between bi-sup group and non-bi-sup group in Korean elder subjects with cerebral infarction (CI). The study group was composed of patients with CIwho were admitted to one of the thirteen Korean oriental medical hospitals participating in this study from 2009 to 2010. A total of 670 CI patients, including 416 with bi-sup group and 254 with non-bi-sup group, participated in this study. Genotype of G-607C was conducted by primer extension using TaqManprobe and five percent of subjects were re-genotyped by direct sequencing to confirm the accuracy of the genotyping. The association of the SNP with the bi-sup group versus non-bi-sup group was performed by multiple logistic regression. Frequency of C allele in bi sup was 45.75% which was significantly lower than 56.69% in non-bi-sup (P=0.0043, OR=0.628 [0.453-0.864]). Subjects with GC or CC type in bi-sup was also 72.36%, that was also small compared with 78.35% in non-bi-sup (P=0.0467, OR=0.675 [0.458 0.994]). These results suggest that G-607C might be used as a diagnostic genetic marker for bi-sup in stroke patients and in the development of personalized medical care. PMID- 26885085 TI - Kimura's disease: risk factors of recurrence and prognosis. AB - OBJECTIVES: The aim of this study was to evaluate risk factors for recurrence and prognosis of Kimura's disease. METHODS: In this study, 32 patients received surgery alone, surgery followed by steroids orally and surgery followed by radiotherapy respectively from 2003 to 2015 (male/female: 27/5, ages: 6-64 years). Retrieval of clinical data and follow-ups have been done. The clinical features used as variables include age, gender, location, multiplicity, laterality, size, duration, primary outbreak, smoking, eosinophils, systemic disease and remedies. Statistical analysis including Kaplan-Meier method, Fisher's exact test, Kruskal-Wallis H test, Mann-Whitney U-test and Cox proportional hazard regression model were performed with the SPSS 17.0. The threshold of statistical significance was set at P=0.05. RESULTS: Median recurrence time was 29 months (2.42 years) after discharged and 56.3% patients relapsed. High recurrence rate was significantly associated with smoking habit (P=0.036). Patients who were diagnosed systemic disease (P=0.027) and were treated with surgery alone (P=0.025) or surgery followed by steroids orally (P=0.025) had short disease-free time. Furthermore, smoking habit (HR=3.383, 95% CI: 1.213-9.433, P=0.02), systemic disease (HR=4.462, 95% CI: 1.443-13.794, P=0.009), surgery alone (HR=4.668, 95% CI: 1.506-14.470, P=0.008) and surgery followed by steroids orally (HR=6.053, 95% CI: 1.330-27.556, P=0.02) were identified as risk factors for the prognosis of Kimura's disease. CONCLUSIONS: Smoking habit, systemic diseases, surgery alone and surgery followed by steroids orally were associated with poor prognosis of Kimura's disease, and they might be prognostic markers of Kimura's disease. PMID- 26885086 TI - Surgical options for posterior tibial plateau fracture. AB - OBJECTIVE: To investigate surgical methods and clinical effectiveness of posteromedial and posterolateral approaches for the posterior tibial plateau fracture. METHOD: 21 cases who received surgery through posterior approaches for the treatment of posterior tibial plateau fractures (PTPFs) were included. RESULTS: 21 cases were subject to follow-up for 12-24 months (an average of 16.2 months). No cases developed incision inflammation, neurovascular injury, internal fixation loosening and breakage. All fractures were healed. No cases developed knee varus and valgus deformity and fracture dislocation. After surgery, Rasmussen score for knee joint functions was 13-30 points (a mean of 24.2). The results were excellent in 12 cases, good in 7 cases and fair in 2 cases. The percentage of excellent and good results was 90.5%. Rasmussen radiology score was 10-18 points (a mean of 15.6 points). The results were excellent in 13 cases, good in 7 cases and fair in 1 cases. The percentage of excellent and good results was 95.2%. 1 case had significant limited range of knee flexion and extension, which was improved after phase II release under arthroscopy combined with function exercise. 2 cases developed traumatic arthritis, which was relieved after intra-articular injection with sodium hyaluronate and oral nonsteroidal anti-inflammatory drug. CONCLUSION: The posteromedial and posterolateral approaches for PTPF is good for reduction and fixation of PTPF. The approaches have benefits such as clear exposure, convenient placement of internal fixation, less trauma and good clinical outcome. PMID- 26885087 TI - Prostate cancer: a comparison of the diagnostic performance of transrectal ultrasound versus contrast enhanced transrectal ultrasound in different clinical characteristics. AB - To determine whether contrast-enhanced transrectal ultrasound (CE-TRUS) is superior to transrectal ultrasound (TRUS) on diagnosis of prostate cancer, 317 patients were processed TRUS examination with or without SonoVue, then biopsy was performed. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of two techniques were compared in multiple subgroups of PSA level, Digital rectal examination (DRE) and prostate volume on biopsy results. In PSA 4-10 ng/ml and DRE negative groups, CE-TRUS had greater sensitivity and accuracy compared with TRUS by patient (P = .004 and .003; .013 and .005 respectively) and greater sensitivity, accuracy, PPV and NPV by core. When prostate volume was 45-65 ml, CE-TRUS had greater specificity and accuracy by patient and all diagnostic performances were statistically significant by core. CE-TRUS is superior to TRUS on diagnosis of prostate cancer in a designed patient population with lower PSA level, DRE negative findings and modest prostate volume. PMID- 26885088 TI - Serum osteocalcin levels are inversely associated with the presence of nonalcoholic fatty liver disease in patients with coronary artery disease. AB - Osteocalcin plays roles in energy, glucose, and lipid metabolism. Consequently, the relationship between osteocalcin level and nonalcoholic fatty liver disease (NAFLD) is of interest. The present study explored the possible correlation between serum osteocalcin levels and NAFLD in patients with CAD. The study enrolled 174 inpatients diagnosed with CAD by coronary angiography (CAG). The presence of fatty liver disease was confirmed by abdominal ultrasonography. NAFLD was diagnosed using the working definition of the revised guidelines for the management of NAFLD published by the Chinese Liver Disease Association. Serum osteocalcin levels were determined using electrochemiluminescent immunoassays. Patients with NAFLD had lower serum osteocalcin levels than those without NAFLD [16.2 (14.2-23.8) vs. 20.7 (15.6-26.2) ng/mL, P<0.05]. After adjustment for gender and age, serum osteocalcin levels correlated with the presence of NAFLD (r=-0.260, P=0.010), fasting plasma glucose level (r=-0.230, P=0.023) and glycated hemoglobin A1c level (r=-0.229, P=0.023). Osteocalcin was an independent factor for the presence of NAFLD (beta=-0.097, P=0.025). These data suggested that serum osteocalcin levels were negatively associated with the presence of NAFLD in patients with CAD. PMID- 26885089 TI - Detection of microsatellite instability in gastric cancer and dysplasia tissues. AB - OBJECTIVE: We aimed to investigate the association between gastric cancer and microsatellite instability (MSI) in the present study. METHOD: Phenol-chloroform method was employed for DNA extraction from the cancer tissues of 65gastric cancer patients and the dysplasia tissues and normal control tissues of 32 non gastric cancer patients. The microsatellite loci Bat25, Bat26, D2S123, D5S346 and D17S250 were detected by using PCR-SSCP silver staining technique, and the MSI of the gastric cancer tissues and the precancerous tissues was analyzed. RESULTS: Of 65 gastric cancer cases, MSI was detected in 43 cases, with the detection rate of 66.2%. There were 13 cases showing MSI-H and 30 cases showing MSI-L, accounting for 30.2% and 69.8%, respectively. Among 32 cases of dysplasia tissues, MSI was detected in 10 cases, with the detection rate of 31.3%. Two cases of dysplasia tissues showed MSI-H and 8 cases showed MSI-L, accounting for 20.0% and 80.0%, respectively. CONCLUSION: Gastric cancer patients had a high detection rate of MSI. It is speculated that MSI is another molecular mechanism of carcinogenesis and may serve as a sensitive diagnostic indicator of gastric cancer. PMID- 26885090 TI - Composite tissue flap at perforating branches of saphenous artery: a new design for repairing composite tissue defects in anterior knee. AB - So far it has been difficult to repair and reconstruct the composite tissue defects in knee. Saphenous artery flap has been widely used to repair complex wounds, but the design and clinical application of composite tissue flap at perforating branches of saphenous artery were not reported. In this research, we design a new composite tissue flap by carrying fascial flap in the medial gastrocnemius muscle with perforators flap in saphenous artery to repair and reconstruct the composite tissue defects in knee. By anatomic observation and analysis, we find that there exists blood-supply in netty form among saphenous arteries, medial artery below the knee, intermuscular branch in high-order position of posterior tibial artery and perforating branch in medial artery of calf. We chose saphenous artery as blood-supplying artery; utilized the netty blood-supplying mode in middle-up and medial part of shank; cut the composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle; reconstructed the ligamentum patellae using medial head of gastrocnemius muscle and Achilles's tendon; and covered the wounds at front side of knee with flap. Composite tissues were survived completely, free from infection at wounds and exosmosis of joint fluid. Motion function of knee joint proved satisfactory, and ambulatory function was recovered. There was no complication in donor site. Composite tissue flap at perforating branches of saphenous artery with fascial flap carried in the medial gastrocnemius muscle is one of the most ideal solutions for repairing the composite tissue defects at front side of knee joint. PMID- 26885091 TI - Does estrogen receptor determination affect prognosis in early stage breast cancers? AB - ER+ and ER- tumors exhibit different histopathological and clinical properties. Receptor determination exists as a marker with predictive value rather than prognostic importance. Patients with invasive breast cancer (n=2849) were investigated retrospectively between 1981 and 2013. Patients were separated to four subgroups, as follows: ER+; non-luminal HER2+; ER-/PR-/HER2-; ER-PR+. We investigated the effects of ER positivity on long-term survival in breast cancers, by considering their pathological properties, surgical method applications, chemotherapy preferences, and combined hormonal treatments with regard to ER, PR and HER2 status. ER+ cases were premenopausal, and they existed with low-grade, small-sized and early stage tumors (P<0.05). One thousand three hundred and eighty five cases (68.6%) were administered chemotherapy, which was followed by hormone therapy. Non-luminal HER2+ tumors were found to exhibit longer survival, when compared to triple negative and ER- tumors (P=0.010). Triple negative cases had the shortest survival rates; survival values determined in the HER2+ and ER-/PR+ cases were found to be between the survivals of ER+ and TN tumors. ER, PR and HER2 positivity was not concomitant with a risk of recurrence (P>0.05). Furthermore, recurrence risk rose significantly when age, tumor stage and tumor grade increased (P<0.05). ER+ tumors are observed in women of advanced age, but have a good clinical response. Currently, receptor determination is still generally preferred as a practical application. ER analysis in the early stage breast cancers for women of advanced ages must be considered as an indicator of anti-estrogenic therapy administration, rather than prognostic importance. PMID- 26885092 TI - Prophylaxis on gout flares after the initiation of urate-lowering therapy: a retrospective research. AB - The objective of this study was to evaluate the efficacy and safety associated with treatment available to prevent an acute attack of gout when initiating a urate-lowering therapy (ULT). We retrospectively reviewed patients who were diagnosed with gout and treated with ULT during the period from January 2000 to January 2014. They were divided into three groups, 75 patients without prophylaxis treatment, 103 patients treated with etoricoxib, and 129 patients with colchicine treatment. Both demographic and clinical characteristics associated with gout were analyzed. At baseline, demographic and clinical characteristics were generally similar in three groups. SU target level was achieved in 49.3% of the patients without prophylaxis treatment, 66.4% in the etoricoxib group and 65.1% in colchicine group, respectively. During the first 16 weeks, patients without prophylaxis treatment exhibited higher flare rates than patients in other two groups. However, no statistically significant difference was observed between patients in etoricoxib group and colchicine group. In the 16 24 weeks, the proportion of patients who reported flares were all decreased similarly in three groups. The mean number of acute gout flares per patient and gout flare days per patient was significantly higher in patients without prophylaxis treatment than patients in other groups. The mean number of acute gout flares was lower (4.2+/-2.3 vs 3.2+/-1.8) in patients with etoricoxib treatment than that in patients with colchicine treatment. Gout flare days per patient were significantly higher in patients without prophylaxis treatment. Compared to colchicine group, gout flare days per patient in etoricoxib were lower (1.2+/-0.5 vs 2.6+/-0.6). In term of AEs, patients receiving colchicine had higher rates of gastrointestinal AEs than those who received etoricoxib. In summary, our survey revealed that etoricoxib was more effective and safe than colchicine in preventing acute attack during ULT. PMID- 26885094 TI - Correlation between body mass index of Chinese males and assisted reproductive technology outcome. AB - OBJECTIVE: To investigate the relationship between male's body mass index (BMI) and the outcome of assisted reproductive technology (ART). In this retrospective study, we analyzed the data from 729 cycles of female patients aged 38 years or less, with normal BMI and who received IVF treatments between January, 2013 and June, 2014. The patients were divided into normal weight (n = 358), overweight (n = 267), and obese (n = 104) groups according to the BMI of their male partners. Embryonic development and pregnancy outcomes in these three groups were compared. RESULTS: With increasing BMI, fertilization rates decreased proportionately (P < 0.05); but embryonic cleavage rates and effective embryo rates were not significantly affected (P > 0.05). There was no significant difference in implantation rates, pregnancy rates, or early miscarriage rates (P > 0.05) among the three groups. CONCLUSIONS: High male BMI affects fertilization rate with ART; and we recommend that men of reproductive age adjust their lifestyles accordingly and make efforts to control their weight. PMID- 26885093 TI - Consistency analysis of contrast-enhanced ultrasound and contrast-enhanced CT in diagnosis of small hepatocellular carcinoma. AB - To compare the consistency of contrast-enhanced ultrasound (CEUS) and contrast enhance CT (CECT) in diagnosis of 1~2 cm and 2.1~3 cm small hepatocellular carcinoma (HCC) and evaluate the value of CEUS in diagnosis of HCC. METHODS: A total of 74 patients (89 lesions) with small HCC and cirrhosis background were retrospectively analyzed. All of the eighty-nine lesions were confirmed by histopathological examination of surgical samples or needle biopsy. All the cases were divided into 1~2 cm group and 2.1~3 cm group. The CEUS and CECT enhanced pattern and diagnosis results of the two groups were compared and the consistency between the two imaging methods were statistically analyzed. RESULTS: In the diagnosis of 1.0-2.0 cm HCC, CEUS and CECT had a moderate consistency in arterial phase, CEUS showed a tolerable consistency with CECT in portal venous and delayphase. The two imaging methods have a better consistency for the diagnosis in 2.1-3.0 cm HCC. CONCLUSION: CEUS can be used as a supplement to provide important diagnostic information in clinical practice when positive results or definite diagnoses cannot obtain. PMID- 26885095 TI - One center experience in China. AB - OBJECTIVE: To investigate the outcomes and prognostic factors for patients with coronary artery disease and low left ventricular ejection fraction (LVEF<=40%) undergoing off-pump coronary artery bypass grafting OPCAB). METHODS: From 2001 to 2004, 71 patients with low EF undergoing OPCABG in our hospital, the mean age is 65.0+/-9.0 years (from 37 to 81), 49 males and 16 females, the mean EF was 33.8+/ 5.0%. Regular follow-up evaluation was completed. Draw the Kaplan-Meier survival curves, Use the log-rank test and Cox regression model to find out the factors that affect the long-term result. RESULTS: 71 low LVEF patients, 6 patients died perioperative, 63 patients discharged successfully, the follow-up time was 64.9+/ 30.4 months. 6 patients lost of follow up, 19 patients died during follow-up including 10 patients (15.9%) who had cardiac-related death. The survival rate at 1, 3, 5 and 8 years was 95.1%, 93.3%, 86.3%, 77.7%, respectively. Univariate analysis shows EF<=30% and acute myocardial infarction within 30 days are risk factors for the long-term survival (P<0.05). Cox regression analysis showed that EF<=30% (RR=6.446, P<0.05) and acute myocardial infarction within 30 days (RR=5.993, P<0.05) are two independent risk factors for the cardiac-related death after discharge. CONCLUSIONS: The patients with low eject fraction ventricular have satisfactory outcomes after OPCAB. LVEF<=30% and acute myocardial infarction within 30 days are two independent risk factors that affect the long-term outcome. PMID- 26885096 TI - Low expression of GNAI3 predicts poor prognosis in patients with HCC. AB - PURPOSES: This study was performed with an aim to explain the underlying role of GNAI3 on the prognosis of patients with HCC. METHODS: The expression of GNAI3 at protein level was detected with the utilization of Immunohistochemistry (IHC). Chi-square test was conducted to assay the relationship between GNAI3 expression and clinical parameters of HCC patients. The correlation between expression level of GNAI3 and survival time after surgeries of HCC patients was evaluated by Kaplan-Meier method. Finally, the Cox regression was established to evaluate the relationship between GNAI3 expression and the prognosis of patients with HCC. RESULTS: In this study, the negative rate of GNAI3 expression in HCC samples was about 76.6%, which was significantly higher than that in paired normal specimens (12.5%). Result showed that there was no correlation between GNAI3 expression and age, gender, liver cirrhosis and vein invasion (P>0.05), but tight relationship between GNAI3 expression and TNM stage and tumor size was found (P<0.05). The following Kaplan-Meier analysis result illustrated that negative expression of GNAI3 induced high mortality of HCC patients. Cox regression result revealed that GNAI3 might be a biomarker for prognosis of patients with HCC (HR: 0.218, P=0.016, 95% CI 0.063-0.750). CONCLUSION: Generally, results of this study demonstrated that expression of GNAI3 shared a tight relationship with the prognosis of patients with HCC. Therefore, GNAI3 could be considered as a novel index for prognosis of patients with HCC. PMID- 26885097 TI - Association between genetic polymorphism in NFKB1 and NFKBIA and coronary artery disease in a Chinese Han population. AB - OBJECTIVES: Prior studies have demonstrated NF-kappaB plays an important role in the development and progression of inflammatory diseases. The aim of this study was to investigate whether promoter polymorphisms in NFKB1 and NFKBIA gene are associated with coronary artery disease (CAD) in a Chinese Han population. METHODS: A total of 1140 Han CAD patients and 1156 Han control subjects were genotyped for 4 single-nucleotide polymorphisms (SNPs) in the promoter region of NFKBIA gene (rs3138053, rs2233406, rs2233409) and NFKB1 gene (-94 ins/del ATTG, rs28362491) by using the TaqMan SNP genotyping assays, and then NFKBIA haplotype blocks were reconstructed according to our genotyping data. RESULTS: For total, men, and women, the distribution of genotypes, alleles of rs3138053, rs2233406, rs2233409 and haplotype polymorphisms showed no significant difference between CAD cases and controls. None of the studied NFKBIA SNPs were associated with CAD. For total, men, and women, there was significant difference in the distribution of the genotypes (P=0.001, P=0.024, P= 0.022) and alleles (P=0.001, P=0.012, P=0.031) of rs28362491 in CAD cases and controls. For total, men, and women, the rs28362491 was associated with increased risk of CAD in a recessive model after adjustment for covariates (OR=1.505, 95% CI 1.190 to 1.903, P=0.001; OR=1.469, 95% CI 1.082-1.993, P=0.014; OR=1.622, 95% CI 1.118 to 2.352, P=0.011, respectively). CONCLUSIONS: In our study, the -94 ins/del ATTG polymorphism in NFKB1 promoter is associated with CAD susceptibility in Chinese Han population, providing a new insight into the genetics of CAD in Chinese Han population. PMID- 26885098 TI - Comparison of complete and incomplete excision of deep infiltrating endometriosis. AB - OBJECTIVE: To compare the efficacy and safety of complete and incomplete excision of deep infiltrating endometriosis (DIE). METHODS: Ninety-three women who underwent complete excision (n=55) or incomplete surgery of DIE (n=38) between January 2011 and December 2013 were included in this retrospective cohort study. Surgical data, and follow-up information of the patients were analyzed. RESULTS: Eighty-five women (91.4%) returned for their follow-up after the operation. The mean follow-up time was 18.3+/-8.7 months. The complete excision group had a significantly higher complication rate than the incomplete excision group (9.1% VS 0%, P<0.001). The decrease of visual analog scale (VAS) scores were more significant (5.6+/-3.9 VS 2.9+/-3.3, P=0.001), and the postoperative recurrence rate is significantly lower (3.9% VS 35.3%, P=0.000) in the complete excision group than that in the in-complete surgery group. The palliative incomplete excision had a comparable pregnancy rate and comparable quality of life in most aspects, except psychological score. And in the in-complete excision patients, administration of post-operative GnRH agonist had a post-treatment improvement of VAS score similar with the complete excision patient (4.5+/-3.2 versus 5.6+/-3.9, P=0.272). However, the recurrence rate were still significantly higher (29.4% VS 3.9%, P=0.000). CONCLUSIONS: Comparing with incomplete excision, the complete excision of DIE significantly decreased the post-operative pain and the recurrence rate. Although incomplete excision with post-operative GnRHa is efficient with respect to pain, the side effects of the drugs and the recurrence rate after cessation of the drugs must be considered. So complete excision of DIE is the first surgical treatment of choice. PMID- 26885099 TI - Risk factors associated with diabetic retinopathy onset and progression in diabetes patients: a Taiwanese cohort study. AB - Diabetic retinopathy (DR) is a common complication of type 2 diabetes mellitus (T2DM) and the leading cause of adult blindness. This study aimed to clarify the risk factors associated with DR onset and progression in patients with T2DM in Taiwan. This retrospective analysis enrolled 743 T2DM patients, including 170 with DR and 573 without DR at baseline who were enrolled in the Diabetes Shared Care Program. The average follow-up period was 2.9 years. Variables, including demographic characteristics, DM duration, anthropometric data and clinical laboratory results, were compared between patients with DR at baseline, those with new-onset DR, and patients without DR using a chi-squared test and one-way ANOVA. A multivariate Cox proportional hazards model was performed to identify risk factors associated with progression of preexisting DR or new-onset DR. During the follow-up period, 38 (22.4%) patients with preexisting DR experienced disease progression, and 91 (15.9%) patients had new-onset DR. Multivariate analysis revealed that the presence of neuropathy (HR: 3.96, 95% CI: 1.84, 8.53) and diastolic blood pressure (HR: 1.05, 95% CI: 1.02, 1.08) were associated with increased risk of DR progression (both P < 0.001). Factors associated with new onset DR included neuropathy, systolic BP, cholesterol, and updated mean of HbA1c (all P <= 0.001). The risk factors associated with DR onset and progression in Taiwanese patients with T2DM are different. Neuropathy and blood pressure increased the risk of both DR onset and progression; however, the risk of DR onset was also increased with updated mean of HbA1c and cholesterol. PMID- 26885100 TI - Comparative evaluation of CT-based and PET/4DCT-based planning target volumes in the radiation of primary esophageal cancer. AB - PURPOSE: To compare planning target volume (PTV) defined by PET combined with 4DCT to 3DCT and 4DCT. METHODS: Eighteen (18/30) esophageal cancer patients who underwent 3DCT, 4DCT and (18)F-FDG PET-CT thoracic simulation with SUVmax>=2.0 of the primary volume were enrolled. CTV3D was formed on 3DCT by adding a margin of 30 mm in cranial-caudal direction and 5 mm in transversal direction. PTV3D was defined using a 10 mm margin to CTV3D and CTV4D was obtained by fusion of CTV from ten phases of 4DCT. A 5 mm margin for setup errors to CTV4D was to form PTV4D. BTVPET was generated with the assumption that motion was captured in PET images using a thresholding methods: 20% SUVmax. CTV(PET) 4DCT was calculated by the union of BTVPET and CTV4D, and a 5 mm margin to CTV(PET) 4DCT was used to form PTV(PET) 4DCT. The geometrical differences of the targets were evaluated. RESULTS: Statistically significant differences were observed among CTV3D, CTV4D and CTV(PET) 4DCT (CTV(PET) 4DCT>CTV4D>CTV3D, P=0.000-0.038). PTV3D, PTV4D, and PTV(PET) 4DCT also differed significantly from each other (PTV(PET) 4DCT>PTV4D>PTV3D, P=0.000-0.048). The DI of PTV3D in PTV(PET) 4DCT was significantly larger than that of PTV3D in PTV 4D (P=0.042). There were no significant differences between the DI of PTV4D in PTV3D and PTV(PET) 4DCT in PTV3D (P=0.118). CONCLUSIONS: As demonstrated by the assessment of the geometrical differences in PET/4DCT-based and 3DCT-based PTV, PET/4DCT could affect not only the volume of PTV but also its shape. PMID- 26885101 TI - All about ketamine premedication for children undergoing ophtalmic surgery. AB - Ketamine is a non-barbiturate cyclohexamine derivative which produces a state of sedation, immobility, analgesia, amnesia, and dissociation from the environment. One of the most important advantages of ketamine premedication is production of balanced sedation with less respiratory depression and less changes in blood pressure or heart rate. As its effects on intracranial pressure, the possible effect of ketamine on intraocular pressure has been controversial overtime. In this study, we aimed to demostrate all the advantages and possible side effects of ketamine premedication in 100 children with retinablastoma undergoing ophthalmic surgery. All the children were premedicated with ketamine 5 mg kg(-1) 15 minutes before the examination orally and peroperative complications, reaction to intravenous catheter insertion, need for additive dose and intraocular pressures of children were recorded. We showed that ketamine administration orally is a safe and effective way of premedication for oncologic patients undergoing examination under general anaesthesia. The incidence of agitation, anxiety at parental separation and reaction to insertion of intravenous catheter was very low while adverse side effects were seen rarely. Intraocular pressure which is very important for most of the ophthalmic surgery patients remained in normal ranges. PMID- 26885102 TI - Relationship between manganese superoxide dismutase (MnSODAla-9Val) and glutathione peroxidase (GPx1 Pro 197 Leu) gene polymorphisms and alopecia areata. AB - OBJECTIVE: The role of the oxidative stress in alopecia areata (AA) has been studied by several researchers in a few studies with conflicting results. These results suggested that lipid peroxidation and alterations in the oxidant antioxidant enzymatic system may play a role in the pathogenesis of AA. Therefore, we aimed to examine the possible associations between the MnSOD Ala 9Val and GPx1 Pro 198 Leu polymorphisms and AA susceptibility and disease progression in Turkish population. METHODS: The study group consisted of 119 unrelated patients with AA and 104 unrelated healthy controls with no scalp lesions in their personal history or on clinical examination. Genotyping was performed to identify MnSOD Ala-9Val and GPx1 Pro 198 Leu polymorphisms by a method based on PCR amplification and detection of polymorphisms with hybridization probes labeled with fluorescent dyes. Genotype and allele frequencies were compared between patients with AA and healthy control subjects. RESULTS: There was no significant difference between the MnSOD Ala-9Val SNP genotype distributions and allele frequencies of the AA patients and the control group (P=0.168 and P=0.820, respectively). There was not any association between clinical and demographical features of the study patients with AA and MnSOD Ala 9Val and GPx1 Pro 198 Leu polymorphism genotypes except gender. CONCLUSIONS: This study is unique since an investigation to reveal the possible associations between the MnSOD Ala-9Val and GPx1 Pro 198 Leu polymorphisms and AA susceptibility and in Turkish population. PMID- 26885103 TI - Changes in sleep architecture and quality in minimal hepatic encephalopathy patients and relationship to psychological dysfunction. AB - OBJECTIVES: We examined changes in sleep quality and architecture in patients with minimal hepatic encephalopathy (MHE) and the impacts of sleep disruption on patient physical and psychological health. METHODS: Ninety-eight MHE patients were examined by polysomnography (PSG) and the Pittsburg sleep quality inventory (PSQI). In addition, patients completed the SAS, SDS, and SCL-90 to examine the relationship between sleep quality and psychological health. RESULTS: Mean relative durations of Stage 1 and Stage 2, sleep latency, microarousal frequency, and total sleep time (TST) were all lower in MHE patients compared to healthy controls (P<0.05 for all). Similarly, SWS and REM stage durations, REM latency, sleep maintenance rate, and sleep efficiency were lower than controls (P<0.01 for all). Mean PSQI scores were lower in MHE patients. Total SAS, SDS, and SCL-90 scores, as well as all SCL-90 subscores, were significantly higher in the MHE group (P<0.05), indicating significant psychological dysfunction. Longer SWS, longer REM, and lower microarousal frequency were associated with improved sleep quality (P<0.05), while shorter SWS and REM led to dyssomnia and daytime functional disturbance (P<0.05, P<0.01). Longer REM latency and higher microarousal frequency were associated with higher PSQI scores (P<0.05, P<0.01), while longer SWS, longer REM, and higher sleep maintenance rate were associated with lower PSQI scores (P<0.05, P<0.01). Finally, total PSQI score and sleep efficiency subscore were positively correlated with total SCL-90 and most SCL-90 subscores (P<0.05). CONCLUSIONS: MHE patients suffer from multiple subjective dyssomnias and changes in sleep architecture that are strongly correlated with psychological dysfunction. PMID- 26885104 TI - A comparison of the outcome of CPR according to AHA 2005 ACLS and AHA 2010 ACLS guidelines in cardiac arrest: multicenter study. AB - The aim of this study was to evaluate whether there is a difference in the return of spontaneous circulation (ROSC) and survival with sequel-free recovery rates between the patients who underwent cardiopulmonary resuscitation (CPR) according to 2005 and 2010 guidelines. This study was conducted in the Bakirkoy Dr. Sadi Konuk and Kartal Lutfi Kirdar Training and Research Hospital between dates of October 2010 and 28 February 2011 after approval of Ethics Committee. In the first months of the study, CPR was performed according to AHA 2005 ACLS guidelines (Group-1), while CPR was performed according to AHA 2010 ACLS guidelines after November 2010 (Group-2). Patients were assessed for neurological deficit with Cerebral Performance Categories Scale. Mean age was found as 69.01+/ 13.05 (minimum: 21, maximum: 92) in 86 patients included. Of the 33 patients underwent CPR in the Group 1, ROSC was achieved in 51.5%; and 6.1% of these patients were discharged. Of the 53 patients underwent CPR in the Group 2, ROSC was achieved in 37.7%; and 9.4% of these patients were discharged. Although the number of living patients in Group 2 was higher than Group 1, the difference was not found statistically significant (5 versus 2), (P>0.05). But, neurological outcomes were found better with 2010 compared to 2005 guidelines (3/7 versus 0/2 good cerebral performance). It was found that the 2005 CPR guidelines practices in ED were more successful than the 2010 CPR guidelines practices in ROSC, but less successful in the rate of discharge from hospital and neurological sequel free discharge rate. PMID- 26885105 TI - Effect of transsphenoidal surgery and standard care on fertility related indicators of patients with prolactinomas during child-bearing period. AB - OBJECTIVE: To explore the surgical therapeutic effects in the endocrine and reproductive system of women with prolactinoma at child-bearing age, and to investigate the potential influencing factors for therapeutic outcome. METHODS: This retrospective study was performed using the medical records of 99 cases of female patients with pituitary PRL adenomas at child-bearing age, who underwent transsphenoidal surgery and took standard perioperative care from January, 2013 to June, 2013 in Huashan hospital, in which micro adenoma (<=1 cm) of 68 cases, large adenomas (> 1 cm) of 31 cases, 88 cases were total resection, 9 cases were subtotal resection, and 2 cases were massive resection. Retrospective study on the preoperative serum level of PRL, menstruation, galactorrhea and reproductive function, etc. Patients were followed up in 1, 3, 6 and 12 months after operation for endocrine indicators, the situation of menstruation and pregnancy. RESULTS: Overall, 88.9%, 9.1%, and 2% patients underwent total, subtotal, and massive resection of prolactinoma in 99 cases of patients. Before accepting transsphenoidal surgery and standard care, all 99 cases with serum PRL level higher than normal 25 ng/ml, 71.7% (71 cases, all total resection) patients had their serum PRL < 25 ng/ml on the first day after surgery, and micro adenomas remission rate of 80.9% (55 cases) was significantly higher than 51.6% of large adenomas (16 cases) (P < 0.05); the postoperative PRL of 11 cases of total or massive resection in patients were not back to normal, Chi-square test results showed that the PRL remission rate after total resection were significantly higher than that of subtotal or massive resection (P < 0.01). 67.3% (66/98) irregular menstruation patients had menstruation recovery after surgery, in addition, total resection of the tumor, micro- adenoma, preoperative PRL < 200 ng/ml and first day of postoperative PRL <=25 ng/ml were favorable factors for menstrual improvement (P < 0.05). 83.6% (51/61) of patients with galactorrhea symptoms got alliviated after surgery, but had no association to the types of tumor (P > 0.05). 14 patients out of 17 infertility patients got pregnant after surgery. CONCLUSION: Transsphenoidal operation combining standardized nursing measures is an effective way to treat pituitary PRL adenoma, and it has high cure rate on abnormal menstruation caused by pituitary PRL adenoma which can recover the fertility of female patients. The preoperative serum level of prolactin could be used as an indicator for postoperative improvement in the endocrine system. The serum level of prolactin on the first day after operation could accurately reflect prognosis, so be regarded as one of the assessment factors for surgical therapeutic effect. PMID- 26885107 TI - Efficacy and safety of cyclophosphamide combined with mycophenolate mofetil for induction treatment of class IV lupus nephritis. AB - The present study aimed to evaluate the efficacy and safety of combination of cyclophosphamide (CTX) and mycophenolate mofetil (MMF) as induction treatment in Chinese patients with class IV lupus nephritis (LN). 82 patients were randomly divided into control (CTX, n=40) and test (CTX+MMF, n=42) groups, and they received monthly dose of 0.75 g/m(2) of body surface area of CTX and monthly dose of 0.4 g/m(2) CTX plus 1.0 g/d MMF, respectively. Patients were followed up for six months after treatment; and their efficacy rates, complete remission rates, adverse events, and certain indices in blood were compared between the two groups. Compared with the baseline levels, significant differences in the levels of hemoglobin, urinary proteins, albumin, serum creatinine, erythrocyte sedimentation rate, complement C3 and anti-dsDNA were observed after treatment in both groups (P<0.05). While the two groups did not differ significantly after treatment (P>0.05). There was a trend toward higher complete remission (54.8%) and efficacy rates (88.1%) after treatment in the test group without statistical significance. However, the incidence rate of gastrointestinal reactions (7.1%) and infections (11.9%) in the test group were significantly lower than the control group (P<0.05). The efficacy of lower dose of CTX combined with MMF as induction therapy for LN was not lower than the traditional treatment with CTX. Moreover, the low dose of CTX in combination with MMF could result in lesser adverse events and improved safety. PMID- 26885106 TI - Effect of rosuvastatin dose-loading on serum sLox-1, hs-CRP, and postoperative prognosis in diabetic patients with acute coronary syndromes undergoing selected percutaneous coronary intervention (PCI). AB - OBJECTIVE: To investigate the effect of rosuvastatin dose-loading on serum levels of lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1) and high sensitivity c-reactive protein (hs-CRP) and postoperative prognosis in patients with diabetes and non-ST segment elevation acute coronary syndromes (NSTEACS) undergoing selected percutaneous coronary intervention (PCI). METHODS: A total of 72 patients with diabetes and NSTEACS were randomized to either the group treated with 20 mg rosuvastatin 12 hours prior to PCI with a second dose administered just before PCI (n = 33), or a control group treated with standard method according guideline (n = 39). Serum levels of sLox-1, hs-CRP, CK-MB, and cTnI were measured prior to PCI, and at 24 hours and 30 days after PCI. The 30-day incidence of major adverse cardiac events (MACE) was recorded in both groups. RESULTS: Compared to pre-PCI, serum levels of sLox-1 and hs-CRP of the two groups were increased at 24 hours after PCI (P < 0.05); the levels of CK-MB and cTnI were also improved (P < 0.01); however, the ascended values of sLox-1, hs-CRP, CK MB, and cTnI were significantly lower in the loading-dose rosuvastatin-treated group than in the control-treated group. Serum levels of sLox-1 and hs-CRP were higher in the loading-dose rosuvastatin-treated group than in the control-treated group at 30 days after PCI (P < 0.05); compared to pre-PCI, the levels of TC and LDL-C were not changed at 24 hours after PCI (P > 0.05) until 30 days after PCI (P < 0.05), but there were no difference between the two groups. The levels of ALT and Scr had no significant difference between the two groups before and after PCI; the 30-day incidence of MACE occurred in 6.06% of patients in the loading dose rosuvastatin-treated group and in 23.08% of patients in the control-treated group (P < 0.05). CONCLUSION: The therapy of dose-loading rosuvastatin for patients with diabetes and non-ST segment elevation acute coronary syndromes undergoing selected percutaneous coronary intervention can attenuate the increase of serum levels of sLox-1, reduce myocardial injury and inflammatory reaction caused by PCI, and also reduce the occurrence of MACE 30 days after PCI. PMID- 26885108 TI - Dosimetric impact of tumor bed delineation variability based on 4DCT scan for external-beam partial breast irradiation. AB - This study sought to evaluate the dosimetric impact of tumor bed delineation variability (based on clips, seroma or both clips and seroma) during external beam partial breast irradiation (EB-PBI) planned utilizing four-dimensional computed tomography (4DCT) scans. 4DCT scans of 20 patients with a seroma clarity score (SCS) 3~5 and >=5 surgical clips were included in this study. The combined volume of the tumor bed formed using clips, seroma, or both clips and seroma on the 10 phases of 4DCT was defined as the internal gross target volume (termed IGTVC, IGTVS and IGTVC+S, respectively). A 1.5-cm margin was added by defining the planning target volume (termed PTVC, PTVS and PTVC+S, respectively). Three treatment plans were established using the 4DCT images (termed EB-PBIC, EB-PBIS, EB-PBIC+S, respectively). The results showed that the volume of IGTVC+S was significantly larger than that of IGTVCand IGTVS. Similarly, the volume of PTVC+S was markedly larger than that of PTVC and PTVS. However, the PTV coverage for EB PBIC+S was similar to that of EB-PBIC and EB-PBIS, and there were no significant differences in the homogeneity index or conformity index between the three treatment plans (P=0.878, 0.086). The EB-PBIS plan resulted in the lowest ipsilateral normal breast and ipsilateral lung doses compared with the EB-PBIC and EB-PBIC+S plans. To conclude, the volume variability delineated based on clips, seroma or both clips and seroma resulted in dosimetric variability for organs at risk, but did not show a marked influence on the dosimetric distribution. PMID- 26885109 TI - Comparison of serum procalcitonin in respiratory infections and bloodstream infections. AB - PURPOSE: This study observed the relationship between procalcitonin (PCT) and results of sputum culture, the relationship between PCT and results of blood culture to evaluate and compare the value of PCT in respiratory and bloodstream infections. METHODS: We analyzed 1616 patients in which PCT and sputum culture were concurrently ordered and analyzed, and 1096 patients in which PCT and blood culture were concurrently ordered and analyzed from January 2014 to May 2015. PCT concentrations were measured by on a Roche Cobas E601 ECL analyzer. RESULTS: The average values of PCT from patients with sputum culture positive and negative were 0.42 (0.17-2.16) and 0.12 (0.06-0.57) ng/ml respectively, and the average values of PCT from patients with blood culture positive and negative were 9.54 (2.10-48.47) and 0.28 (0.10-1.23) ng/ml respectively. In sputum culture, positive rate of PCT in cases with growth of pathogens was 47.1%. In blood culture, positive rate of PCT in cases with growth of pathogens was 89.2%. CONCLUSIONS: PCT is useful in early diagnosis of respiratory infections and bloodstream infections, but the specificity of PCT in diagnosing respiratory infections is not as high as it is in bloodstream infections. PMID- 26885110 TI - Conventional in vitro fertilization maybe yields more available embryos than intracytoplasmic sperm injection for patients with no indications for ICSI. AB - Many physicians suggest that performing ICSI instead of IVF for all cases just because they thought that ICSI yields more available embryos than IVF. However, we found that IVF results in better fertilization per retrieved oocyte (72.12 +/- 19.60% versus 59.54 +/- 21.38%, P < 0.01) and day 3 available embryo per retrieved oocyte rates (54.89 +/- 23.53% versus 50.54 +/- 22.68%, P < 0.05) than ICSI after analysis of 218 cycles using sibling oocytes in combined IVF/ICSI for patients with no indications for ICSI. We also found a positive correlation between the degeneration rate after ICSI, oocyte immaturity rate, and rate of 2 pn per retrieved oocyte obtained from IVF compared to ICSI, as well as the day 3 available embryo rate between IVF and ICSI. It is possible that outcome may be due to more in vitro-matured oocytes achieved in IVF fertilization compared with ICSI fertilization, and a considerable portion of the mature oocytes were degenerated after ICSI. Therefore, it is suggested that ICSI should not be performed in all cases of in vitro conception. IVF is preferable to ICSI for cases in which a relatively low possible fertilization failure occurs in conventional IVF. PMID- 26885111 TI - Paraoxonase-1 and arylesterase activities in patients with colorectal cancer. AB - BACKGROUND: The aim of this study was to evaluate paraoxonase-1 (PON1) and arylesterase (ARE) activities and oxidative stress status in patients with colorectal carcinomas (CRC). MATERIALS AND METHODS: Thirty-three patients (20 male, 13 female) with CRC and 30 healthy controls were enrolled in the study. Blood samples were obtained from the CRC patients before adjuvant therapy. Serum samples from CRC patients and healthy controls were analyzed for PON1 and ARE activities. RESULTS: The PON1 and ARE activities of the patients with CRC were significantly higher compared to those of the control group (PON1 activity is 125.35+/-20.07 U/L for CRC patients and 1.22+/-0.48 U/L for control group, P<0.001; ARE activity is 160.76+/-10.79 U/L for CRC patients). ARE levels showed a positive correlation with smoking status (P=0.04). PON1 activity was higher in colon carcinoma patients (135.95+/-19.3 U/L) rather than rectal carcinoma patients (97.08+/-5.24 U/L) but it was not statistically significant (P=0.72). CONCLUSION: Serum PON1 activity is increased in patients with CRC, and serum ARE levels showed a positive correlation with smoking status. PON1 activity was higher in colon carcinoma patients. There is no other study in literature investigating these activities for CRC patients. It should be reevaluated by larger clinical trials. PMID- 26885112 TI - Vitrified/warmed single blastocyst transfer in preimplantation genetic diagnosis/preimplantation genetic screening cycles. AB - OBJECTIVE: To investigate the single blastocyst transfer in preimplantation genetic diagnosis (PGD)/preimplantation genetic screening (PGS) cycles. METHODS: 80 PGD/PGS cycles undergoing blastocyst biopsy were studied. There were 88 warming cycles during the study period. Only one warmed blastocyst was transferred per cycle. The outcomes were followed up to the infants were born. RESULTS: The embryo implantation rate was 54.55% (48/88). The clinical pregnancy rate was 54.55% (48/88) per transfer cycle and 60% (48/80) per initial PGD/PGS cycle. There was no multi-pregnant in this study. The live birth rate was 42.05% (37/88) per transfer cycle and 46.25% (37/80) per initial PGD/PGS cycle. CONCLUSION: In PGD/PGS cycles, single blastocyst transfer reduces the multiple pregnancy rate without affecting the clinical outcomes. PMID- 26885113 TI - Prospective randomized trial of mesh fixation with absorbable versus nonabsorbable tacker in laparoscopic ventral incisional hernia repair. AB - The aim of this prospective randomized trial was to compare 2 main fixation devices in regard to pain and recurrence in laparoscopic ventral incisional hernia repair (LVIHR). A total of 51 patients were evaluated in this study (n = 25, nonabsorbable tack (NAT) and n = 26, absorbable tack (AT) groups). A visual analogue scale (VAS) was performed on both groups preoperatively and on the postoperative (PO) first day, second week, and sixth month. All patients were followed for recurrence by clinical examination, ultrasonography, and/or abdominal computed tomography. The median follow-up time was 31 months (15-45). The mean age and the mean body mass index (BMI) of the patients were 53.1 +/- 11 years and 34 +/- 5 kg/m(2), respectively. The median defect size was 60 cm(2) (35 150) and median operation time was 110 minutes (40-360). In 2 patients from AT group and 2 from NAT group (7.8%), recurrence occurred. The 2 groups had similar features regarding demographics, operation time, postoperative hospital stay, morbidity, and VAS scores. The 2 fixation methods were found similar for PO pain and recurrence. In our opinion, the choice of either of these fixation methods during surgery should not be based on the concerns of pain or recurrence. AT may be the preferable option in LVIHR due to the lower cost. PMID- 26885114 TI - Delta-aminolevulinate synthase 2 polymorphism is associated with maximal oxygen uptake after Living-high exercise-high training-low in a male Chinese population. AB - OBJECTIVE: Each individual shows great variations to hypoxic training, which may be due to individual differences in genotype or gene polymorphism. delta aminolevulinic acid synthase 2 (ALAS2 ) polymorphism is used as a marker for X linked sideroblastic anemia. This study assessed the ALAS2 polymorphism for an association with response to Living-high exercise-high training-low (HiHiLo) training in Han Chinese males. METHODS: A total of 244 healthy young male subjects of Han nationality were recruited from Northern China for detection of the ALAS2 polymorphism, 72 of whom were then selected for undergoing a four-week HiHiLo training program (i.e., subject to 10 h of hypoxia training daily at 14.5 14.8% O2 exposure, three occurrences of hypoxic training every week at 15.4% O2 level, and normal training at sea level). GeneScan and DNA sequencing were used to analyze ALAS2 polymorphism. Before and after training, the maximal oxygen uptake (VO2 max) in each individual was recorded. RESULTS: A successive cut-point analysis showed that the initial hemoglobin value in individuals with dinucleotide repeats <= 166 bp was significantly higher than in individuals with dinucleotide repeats > 166-bp (P = 0.05). The ?VO2 max and ?rVO2 max after HiHiLo training were significantly higher in individuals with dinucleotide repeats <= 166 bp than in individuals with dinucleotide repeats > 166 bp (P < 0.01). CONCLUSIONS: The compound dinucleotide repeat polymorphism in ALAS2 intron 7 correlated with response to HiHiLo training. Further study will evaluate this ALAS2 SNP as a genetic marker to predict responses to HiHiLo training. PMID- 26885115 TI - Serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies. AB - OBJECTIVE: This study was designed to investigate serum cholesterol levels in middle-aged euthyroid subjects with positive thyroid peroxidase antibodies (TPOAbs). METHODS: We screened 1607 euthyroid subjects aged 35-65 years old. All the subjects were divided into 2 groups (i.e., TPOAb-positive group, n=205; TPOAb negative group, n=1402) according to the level of TPOAb. The subjects were then subgrouped according to serum thyroid stimulating hormone (TSH) levels; those with a TSH level of 0.3-0.99 mIU/L, 1.0-1.89 mIU/L, and 1.9-4.80 mIU/L were classified into the low-normal, mid-range, and high-normal TSH subgroups, respectively). Each TSH group further subdivided into TPOAb-positive and TPOAb negative subgroup. Data regarding the subjects' height, body weight, blood pressure, and levels of serum TSH, TPOAb, fasting plasma glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were collected. RESULTS: Compared with TPOAb-negative subjects, TPOAb-positive patients had higher levels of TSH, TC, and HDL-C (P=0.001, P=0.012, and P=0.049 respectively) with a tendency for increased LDL-C levels (P=0.053). In the low-normal TSH subgroup, subjects with and without TPOAb had similar levels of TSH, TC, HDL-C, and LDL-C (P>0.05). In mid-range TSH subgroup, TPOAb-positive patients had higher HDL-C levels compared to TPOAb-negative subjects (P=0.008) and a tendency for increased TC levels (P=0.121). In the high-normal TSH subgroup, TPOAb-positive patients had higher TSH and TC levels compared to TPOAb-negative subjects (P<0.001 and P=0.046 respectively). CONCLUSIONS: High TPOAb levels above the normal range appears in euthyroid population, dyslipidemia have begun. PMID- 26885116 TI - Association of genetic polymorphisms in PTEN and additional interaction with alcohol consumption and smoking on colorectal cancer in Chinese population. AB - AIMS: To investigate the association of phosphatase and tensin homologue deleted on chromosome ten (PTEN) gene rs3830675, and additional interaction with drinking and smoking on colorectal cancer (CRC), based on a hospital based Chinese case control study. METHODS: A total of 850 subjects (413 males and 437 females) were studied, including 422 colorectal cancer cases and 428 controls. Rs3830675 was selected for genotyping in the case-control study. Logistic regression model was used to examine the association between rs3830675 and colorectal cancer, and additional interaction with alcohol consumption and smoking. RESULTS: The frequencies for rs3830675 (-) alleles was higher in cases than that in controls, (-) allele of rs3830675 was 24.4% in controls and 29.4% in CRC subjects (p=0.005). Logistic analysis showed that the carriers of (-) allele of rs3830675 revealed increased CRC risk than those with (+/+) genotype, adjusted OR (95% CI) was 1.35(1.12-1.98). We found a significant interaction between alcohol consumption and rs3830675, drinkers with (-/-) or (-/+) of rs3830675 genotype have highest colorectal cancer risk, compared to never drinking subjects with (+/+) genotype, OR (95% CI) was 2.57 (1.66-3.33), after covariates adjustment. In addition, we also found that smokers with (-/-) or (-/+) of rs3830675 genotype have highest colorectal cancer risk, compared to never smokers with (+/+) genotype, OR (95% CI) was 3.01 (1.58-6.05). CONCLUSIONS: The (-) allele of rs3830675 was positively with colorectal cancer risk. There was a significant role of interaction of rs3830675 with alcohol consumption and smoking on colorectal cancer. PMID- 26885117 TI - Atorvastatin up-regulates TRIB3 independent of ATF4-CHOP pathway in atherosclerotic patients. AB - BACKGROUND: Macrophage apoptosis triggered by endoplasmic reticulum (ER) stress contributes much to atherosclerosis, especially plaque vulnerability. Activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)-Tribbles 3 (TRIB3) pathway is closely related to the ER stress. This study aimed to investigate the effect of atorvastatin on the ATF4-CHOP-TRIB3 pathway. METHODS: Forty-seven patients were randomized into 80-mg and 20-mg atorvastatin group. Follow-up was performed at weeks 6 and 12, and complete blood chemistry, lipid assay and detection of 5 target genes (tumor protein 53, ATF4, C/EBP, CHOP and TRIB3) in monocytes/macrophages were conducted. Furthermore, the interaction between dosage and duration of therapy was evaluated. RESULTS: After 12-week therapy, patients in both groups experienced significant reductions in ATF4 (P=0.038) and C/EBP (P=0.003) expressions. Tumor protein 53 (P=0.015) and TRIB3 (P=0.045) expressions increased markedly in 80-mg atorvastatin group. However, there was no significant difference in CHOP expression at three time points and between atorvastatin groups. Moreover, there was no interaction between dosage and duration of therapy. CONCLUSIONS: Atorvastatin has an effect on ER stress through ATF4-CHOP pathway. Atorvastatin at a high dose is more likely to increase TRIB3 expression, but this warrants further investigation. PMID- 26885119 TI - Interaction between peroxisome proliferator- activated receptor gamma polymorphism and overweight on diabetic retinopathy in a Chinese case-control study. AB - BACKGROUND: Peroxisome proliferator-activated receptors gamma (PPAR gamma) and overweight were both associated with diabetic retinopathy (DR), so the aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) of PPAR gamma with DR and additional role of gene-BMI interaction. METHODS: A total of 500 patients with T2DM (236 men, 264 women), with a mean age of 54.3 +/- 15.8 years old, were selected, including 247 diabetic retinopathy patients and 253 controls. Four SNPs were selected for genotyping in the case-control study: rs1805192, rs709158, rs3856806, rs4684847. Logistic regression model was used to examine the interaction between SNP and overweight on DR, odds ratio (OR) and 95% confident interval (95% CI) were calculated. RESULTS: The carriers of C allele of the rs1805192 polymorphism revealed decreased DR risk than those with Pro/Pro variants (Pro/Ala+Ala/Ala versus Pro/Pro, adjusted OR (95% CI)=0.86 (0.65-0.96), P=0.012), after adjusting for covariates. We also found that obese subjects with Pro/Ala or Ala/Ala variants genotype have lowest DR risk, compared to obese subjects with Pro/Pro genotype or non- obese subjects with Pro/Ala or Ala/Ala (OR=0.40, 95% CI=0.32-0.63), after covariates adjustment. CONCLUSIONS: Our results support an important association between rs1805192 minor allele (Ala allele) of PPAR gamma and DR, the interaction analysis shown a combined effect of Ala- BMI interaction on DR. PMID- 26885118 TI - Correlation between mimecan expression and coronary artery stenosis in patients with coronary heart disease. AB - OBJECTIVE: This study aimed to investigate the correlation between coronary artery stenosis and Mimecan expression in patients with coronary heart disease (CHD). METHODS: Seventy eight patients with CHD and 80 controls without vascular lesions were recruited into present study. CHD patients were divided into one vessel CHD subgroup, 2-vessel CHD subgroup and multivessel CHD subgroup. ELISA was performed to detect the expressions of serum Mimecan and nuclear factor kappaB (NF-kappaB). RESULTS: When compared with control group, the expressions of serum mimecan gene and NF-kappaB significantly increased in CHD groups (P < 0.05); When compared with one-vessel and two-vessel CHD subgroups, the expressions of serum mimecan and NF-kappaB significantly increased in multivessel CHD subgroup (P < 0.05), significant difference was observed among three subgroups (P < 0.05). The expressions of serum mimecan and NF-kappaB were positively related to the severity of coronary lesions (rmimecan=0.79, rNF kappaB=0.83, P < 0.05). CONCLUSION: Increased expressions of serum mimecan and NF kappaB in CHD patients are related to cardiac insufficiency, which may be ascribed to the binding of NF-kappaB to mimecan gene. PMID- 26885120 TI - Safety of uneventful cesarean section in terms of hemorrhage. AB - OBJECTIVE: Hemorrhage still continues to be reported as one of the leading causes of maternal mortality and morbidity. Intraoperative estimation of the blood loss seems to be complex and misleading as it is impaired by the amount of amniotic fluid and blood from the placenta. The present study was aimed to investigate the safety of intraoperative deciding on an uneventful cesarean section in a low risk patient population. MATERIAL AND METHODS: One hundred patients free from hemorrhage risks and experienced an uneventful elective cesarean section, were included to the study. The decline in hemoglobin and hematocrit values, calculated blood loss, transfusion rate and presence of hemorrhage related symptoms and signs were accepted as the main outcomes of the study. RESULTS: The average preoperative and postoperative hemoglobin values were detected as 12.09+/ 0.18 g/dl and 10.72+/-1.39 g/dl, respectively. The average decrease in hemoglobin was 1.36+/-1.06 g/dl. The observed decrease in hemoglobin values were less than 10% in 34.4% of the patients. The average blood loss was calculated to be 517.06+/-417.55 ml. There were no patients with signs and symptoms of hemorrhage. Cross match transfusion ratio, transfusion probability and transfusion index was calculated as zero. CONCLUSION: The decision of uneventful cesarean section provides obstetricians a safe postoperative and postpartum period after following standardized surgical procedures in terms of hemorrhage and related complications. PMID- 26885121 TI - Cardiac urticaria caused by eucleid allergen. AB - Urticaria is a common allergic diseases, which involve respiratory and digestive system being suffered in some population. Yet, relatively little research has been done on the adverse effect on the heart. We did this research to examine the correlation between the abnormality of ECG in the patients with acute allergic urticaria and the antigen of eucleid. The antigen (allergen of eucleid and other allergens) was used to test the patients with acute allergic urticaria by skin prick test and electrocardiogram was employed to examine the patients with strong positive (moth & caterpillar) eucleid antigen. Strong positive eucleid antigen was identified in 84 cases with abnormal electrocardiographic pattern of diversity. So, the acute allergic skin urticaria caused by eucleid allergen may impose strong effect on the heart and thus lead to allergic cardiac urticaria. PMID- 26885122 TI - Medium-term follow-up of clinically insignificant residual fragments after minimal invasive percutaneous nephrolithotomy: prognostic features and risk factors. AB - Minimal invasive percutaneous nephrolithotomy (MPCNL) has been commonly used in removing urinary stones. However, the detrimental effects of clinically insignificant residual fragments (CIRF) after MPCNL have not been entirely clarified. This study is aimed at investigating the clinical outcomes of CIRF after MPCNL. From July 2004 to June 2010, 1862 cases of urolithiasis underwent MPCNL. 185 cases of CIRF were subsequently diagnosed using CT scanning and followed up. During follow-ups, medical history, physical examination, routine blood and urine tests, subjective symptoms were recorded. A multiple-variable Cox regression was performed to evaluate the prognostic significance of different factors for CIRF after MPCNL. Of 185 cases of CIRF followed up for 31.4 months on average, 58 cases (31.4%) suffered symptomatic episodes, including 30 cases of hematuresis, 21 cases of low urinary tract symptoms and 7 cases of hematuresis complicated with renal colic. The results of Cox regression showed that past history of extracorporeal shock wave lithotripsy (ESWL), CIRF size, hypercalcuria and CIRF located in ureteropelvic junction (UPJ) are independent risk factors for medium-term symptomatic episodes of CIRF after MPCNL. We suggest that regular follow-ups should be considered for patients with CIRFs after MPCNL for timely treatments, especially for those who are hypercalcuria-complicated, have history of ESWL, or suffer relatively large CIRFs located in the UPJ. PMID- 26885123 TI - Relation between the testicular sperm assay and sex hormone level in patients with azoospermia induced by mumps. AB - This study aimed to investigate the relation between the testicular sperm assay (TESA) and sex hormone level or testicular volume in patients with azoospermia induced by mumps. Samples from 52 patients with mumps-induced azoospermia were subjected to TESA, and then the sperm activity was observed microscopically. The sex hormone level was detected with an electrochemical assay, and ultrasound was used to calculate the testicular volume. Of the 52 azoospermia patients, 38 were found to have active sperms through testicular sperm extraction from the opened testis; furthermore, the serum follicle-stimulating hormone (FSH) and luteinizing hormone levels were obviously higher in the non-sperm group than in the sperm group (P < 0.05). Moreover, the testicular volume was smaller in the non-sperm group than in the sperm group; however, there was no significant difference between the two groups (P > 0.05). With the FSH value as a standard, the quantity of sperms was found to be within two times of, or more than two-fold of the normal range. With the testicular volume as a standard, sperms were found in testes with a volume of > 6 mL or < 6 mL. The FSH value and the testicular volume were indicators of the ability of the TESA to obtain sperms. To allow the performance of intracytoplasmic sperm injection, all patients need to undergo TESA. PMID- 26885125 TI - Correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia in Alzheimer's disease and vascular dementia. AB - OBJECTIVE: To discuss the correlation of polymorphism of APOE and LRP genes to cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) and vascular dementia (VD). METHOD: AD cases, VD cases and healthy control cases totaling 237, 255 and 234 were recruited, respectively. The mini-mental state examination (MMSE) was performed to evaluate cognitive impairment. Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were adopted to evaluate BPSD. Apolipoprotein E (APOE) and Low-density lipoprotein receptor-related protein gene (LRP) genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: (1) Frequencies of APOEepsilon4 allele in AD group and VD group were significantly higher than that of the control (P<0.05); (2) MMSE scores of APOEepsilon4 carriers in AD group and VD group were lower than that of non-APOEepsilon4 carriers in the same group (P<0.05); (3) The proportion of APOEepsilon4 carriers presenting with BPSD in AD group was considerably higher that of non-APOEepsilon4 carriers (P<0.05). CONCLUSION: APOEepsilon4 may be the common risk factor for cognitive impairment in AD and VD and the risk factor for BPSD in AD. PMID- 26885124 TI - Prevalence of p.V37I variant of GJB2 among Chinese infants with mild or moderate hearing loss. AB - GJB2 accounts for more than 80% of recessive forms of hereditary hearing loss (HL); however, the correlation between the p.V37I variant of GJB2 and hearing phenotype is controversial. This study aimed to investigate the clinical and epidemiological characteristics of the p.V37I variant in sensorineural hearing loss in Chinese infants (0-3 months). Hearing and gene tests were conducted in 300 infants (aged 0-3 months) with sensorineural hearing impairment and 484 normal infants (aged 0-3 months). Among the 300 hearing-impaired infants, 16 (5.33%) exhibited homozygous p.V37I variation and 7 (2.34%) showed a compound heterozygous p.V37I variation, whereas no homozygous p.V37I (0%) or compound heterozygous p.V37I (0%) condition was found among the 484 normal infants. The hearing impairment ranged from mild to profound in all patients exhibiting the homozygous p.V37I or the compound-heterozygous p.V37I condition, although most patients (61.54%) exhibit mild or moderate HL. Our results indicated that the p.V37I variation of GJB2 mutation is mainly associated with mild or moderate hearing impairment. Therefore, otolaryngologists should also screen the p.V37I variant of GJB2 in patients with mild or moderate HL. PMID- 26885126 TI - Intracytoplasmic sperm injection (ICSI) outcomes of azoospermia with different causes: 107 cases report. AB - This retrospective analysis compared the outcomes of fertilization and pregnancy rates of 107 azoospermia patients treating with intracytoplasmic sperm injection (ICSI). Sperms were obtained by testicular biopsy surgery, with which we used in ICSI subsequently. The outcomes were compared by different kinds of causes leading to azoospermia in the 107 cases. 69 cases of obstructive azoospermia and 38 cases non-obstructive, the fertilization rates were 61.94% and 53.47% respectively, and pregnancy rates were 67.65% and 52.63%. 78 cases with normal volume testes and 29 cases with small testes, the fertilization rates were 70.93% and 48.80% respectively, and pregnancy rates were 66.25% and 50.00%. There was significant difference in fertilization rates between obstructive, non obstructive and normal volume testes, small testes (P < 0.05), but no significant difference in pregnancy rates (P > 0.05). The pregnancy rate was significant difference between female age < 32 and >= 32 whatever the cause of azoospermia was (P < 0.05). Our study reveals that obstructive azoospermia and normal volume testes have higher fertilization rates in ICSI, but the pregnancy rates are only related to female age. PMID- 26885127 TI - Proton pump inhibitors use in hemodialysis patients and serum magnesium levels. AB - Hypomagnesemia is reported in patients who use proton pump inhibitors (PPIs). We investigated the effect of PPIs use on serum magnesium levels in hemodialysis patients. Our study was conducted in a hemodialysis center including 75 end stage renal disease patients. PPI use and duration were investigated. All patients were dialyzed using a dialysate magnesium level of 0.5-0.75 mmol/L. After at least one month of hemodialysis with the mentioned dialysate, laboratory tests were performed. Fifty-four patients (72%) used PPIs while 21 (28%) did not. The mean duration of PPI use was 42.5 +/- 35 months. There was no significant difference between serum magnesium levels of patients who used and did not use PPIs (2.73 +/ 0.3 vs. 2.88 +/- 0.3 mg/dL, P = ns). There were 15 patients (20%) with a dialysate magnesium level of 0.5 mmol/l and 60 patients (80%) with a dialysate magnesium level of 0.75 mmol/L. The mean serum magnesium levels of patients with a dialysate magnesium level of 0.5 mmol/L was 2.45 +/- 0.3 mg/dL while that of patients with a dialysate magnesium level of 0.75 mmol/L was 2.85 +/- 0.3 mg/dL (P<0.0001). In hemodialysis patients, PPI use did not affect serum magnesium levels. The most important factor affecting the serum magnesium levels in hemodialysis patients is the dialysate magnesium concentration. PMID- 26885128 TI - Cardiovascular risk factors in Chinese women with a history of gestational diabetes mellitus. AB - BACKGROUND: Women with a history of gestational diabetes (GDM) are at increased risk of developing cardiovascular diseases compared with normal women. This study aimed to evaluate the cardiovascular risk factors in Chinese women with GDM. METHODS: 453 women with GDM (cases) and 1,180 healthy women (controls) were included in this study. The post-partum examinations included 2 h 75 g oral glucose tolerance tests, lipid profiles, anthropometric measurements (blood pressure, height, weight) and documentation of medical history, diet, and lifestyle. RESULTS: Compared with controls, the risks of abnormal glucose metabolism, obesity, hypertension, metabolic syndrome in women with a history of GDM were 4.61, 1.30, 1.57 and 3.52, respectively. Fasting blood glucose, progestational body mass index (pBMI) and antenatal insulin resistance at antenatal visit were predictors for abnormal glucose metabolism. pBMI and antenatal diastolic blood pressure were predictors for hypertension. pBMI and weight gain during pregnancy were predictors for obesity/overweight. pBMI, antenatal systolic blood pressure and antenatal triglyceride were predictors for metabolic syndrome. CONCLUSIONS: Women with a history of GDM have increased rates of cardiovascular disease risk factors including abnormal glucose metabolism, obesity, hypertension, metabolic syndrome. pBMI is the common independent predictors of cardiometabolic disease in the post-partum. PMID- 26885129 TI - Prognostic value of three pro-nuclei (3PN) incidence in elective single blastocyst-stage embryo transfer. AB - OBJECTIVES: To investigate whether 3PN incidence could lead to a worse pregnancy outcome of elective single blastocyst stage embryo transfer (eSBET). METHODS: This study included 706 eSBET cycles from January 2013 to March 2015. The patients were divided into two groups as follows: group 1 included 286 patients with no 3PN zygotes and group 2 included 420 patients with 3PN zygotes. MAIN OUTCOME MEASURE: female age, endometrial thickness, infertility duration, type of infertility, main etiology of infertility, clinical pregnancy and abortion rate. RESULTS: We observed that there was no significant difference in female age, endometrial thickness, infertility duration and abortion rate between two groups. It's worth noting that the clinical pregnancy rate in 3PN > 0% group was significantly lower than 3PN = 0 group (P = 0.021). CONCLUSIONS: 3PN incidence might make anegative effect on pregnancy outcomes in elective single blastocyst stage embryo transfer. PMID- 26885130 TI - Clinical analyses of endometriosis after conservative surgery. AB - OBJECTIVE: To assess the remission rate and outcome of pregnancy of patients who had moderate and severe ovarian endometriosis after conservative surgery. We also wished to analyze the associated factors of recurrence. METHODS: Weconducted retrospective analyses of 199 cases with stage II-IV ovarian endometriosis who had preserved fertility under laparoscopic surgical treatment. Postoperatively, the 199 patients were divided into three groups: 43 cases underwent surgical treatment alone (group A); 47 were given a gonadotropin-releasing hormone agonist (GnRH-alpha) (group B), and 109 were given mifepristone (group C). Ten cases in group A were infertile, 26 cases in group B, and 38 cases in group C. All patients were followed up for 3 years. This study was approved by the Ethics Committee of Yangpu District Central Hospital. RESULTS: In groups A, B and C, the remission rate was 58.13%, 70.21% and 60.55% and the difference not significant (P=0.384); Recurrence rates were 27.90%, 12.76% and 24.77%, and the difference between them significant (P<0.05). The recurrence rate in group B was the lowest. The natural pregnancy rate after surgery in the three study groups (untreated, GnRH-alpha and mifepristone) was 30%, 34.61% and 28.94% but this difference was not significant. CONCLUSION: Surgery can improve the symptom remission rate and fertility of patients. Postoperative drug therapy does not improve the chance of pregnancy. PMID- 26885131 TI - Twin pregnancy after intracytoplasmic sperm injection in woman aged 49 using autologous oocytes by mild ovarian stimulation: a case report. AB - There were few reports about infertile women aged 45 and above undergoing IVF/ICSI. We are reporting the case of an aged 49 woman who delivered the twins after ICSI using autologous oocytes by mild ovarian stimulation. The patient who presented with 26-year primary infertility was caused by double fallopian tubes obstruction and man oligoasthenozoospermia. We gave her the treatment with mild ovarian stimulation cycle of clomiphene citrate (CC) and follicle stimulating hormone (FSH) undergoing ICSI, and transferred two fertilization-blastocysts. The outcome measured was the live birth. The twins were delivered by cesarean section operation at 37 pregnancy weeks for the moderate pregnancy-induced hypertension. Our study showed that the successof advanced agewomen undergoing ART was feasible to some extent, while, the accompanied risk of pregnancy complications and other issues need to be further evaluated. PMID- 26885132 TI - Duodenal duplication manifested by abdominal pain and bowl obstruction in an adolescent: a case report. AB - Duodenal duplication (DD) is a rare congenital anomaly reported mainly in infancy and childhood, but seldom in adolescent and adults. Symptoms, such as abdominal pain, nausea, vomiting or dyspepsia may present depending on the location and type of the lesion. DD can result in several complications, including pancreatitis, bowl obstruction, gastrointestinal bleeding, perforation and jaundice. Surgery is still the optimal method for treatment, although endoscopic fenestration has been described recently. Here, we report a case of a DD on the second portion of the duodenum in a 17-year-old adolescent complaining of transient epigastric pain and vomiting after meal. We suspected the diagnosis of DD by abdominal computerized tomography and endoscopic ultrasonography. We treated her by subtotal excision and internal derivation. Eventually, we confirmed our diagnosis with histopathological result. PMID- 26885133 TI - Myricitrin inhibits PDGF-BB-stimulated vascular smooth muscle cell proliferation and migration through suppressing PDGFRbeta/Akt/Erk signaling. AB - Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play major pathological processes involved in the development of cardiovascular diseases. As a result, the use of anti-proliferative and anti-migratory agents for VSMCs offers promise for the treatment of vascular disorders. Myricitrin is a naturally occurring phenolic compound which possesses antioxidant and anti-inflammatory activity. In this study, we investigate the inhibitory effect of myricitrin on PDGF-BB-induced VSMCs proliferation and migration. In accordance with these findings, myricitrin induced the arrest of cell cycle progression at G0/G1 phase. Myricitrin also decreased the expressions of G0/G1 specific regulatory proteins including cyclin D1, cyclin-dependent kinases (CDK) 4, cyclin E and CDK2, as well as increased the expression of p21 in PDGF-BB-induced VSMCs. Moreover, myricitrin inhibited PDGF-BB-induced phosphorylation of PDGFRbeta, Akt and Erk1/2. These results suggest that myricitrin plays an important role in prevention of VSMCs proliferation and migration through the G0/G1 cell cycle arrest by PDGF signaling pathway. Thus, myricitrin is effective in reducing atherosclerotic process by blocking proliferation of VSMCs. PMID- 26885134 TI - Extensive epidural extension growth of a glioblastoma: a case report and literature review. AB - It is extremely rare for a glioblastoma to mainly have epidural growth after its invasion of the dura. The present paper reports such a rare case. The patient was a 37-year-old male. After the onset of headache, computed tomography (CT) examination revealed an extradural convex-shaped lesion on the frontal region that was mainly epidural. During the first surgery, the extradural lesion mainly consisted of bloody viscous liquid; therefore, it was misdiagnosed as simple epidural bleeding, and the best diagnosis and treatment opportunity were missed. One month later, a relapse of the disease occurred, with a symptom of exophthalmos. Imaging examination revealed extensive extradural growth of the lesion along the forehead and invasion downwards into the frontal sinus, sphenoidal sinus, ethmoidal sinus and orbit. The second surgery could not completely remove the lesion, and pathological diagnosis of the lesion was a glioblastoma. One month later, the glioblastoma continued to grow, the third operation was performed, this time most of tumor was removed, the treatment was assisted with radiotherapy and chemotherapy, the tumor was controlled effectively, and the patient did well after six months. While reporting this rare case, we also review the cases of glioblastoma invasion of the dura and their growth and the classification of dura invasions, aiming at improving our understanding in cases of glioblastoma invasion of the dura so that we can make timely, accurate diagnoses. PMID- 26885135 TI - Malignant infiltrating intraductal papillary mucinous neoplasm with internal fistula: one case report and clinical practice. AB - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a rare tumor that originates in the pancreatic duct. The diagnosis of benign, borderline or malignant to IPMN is significant in terms of making an appropriate treatment plan and prognosis. This article summarizes our clinical experience of a case report and discussion by literature review. Methods and case report: A 73 year old male patient was admitted for an occupying lesion of the pancreas. The magnetic resonance cholangiopancreatography (MRCP) scan considered IPMN, endoscopic retrograde cholangiopancreatography (ERCP) also confirmed diagnosis of IPMN. Both the biliary and pancreatic duct stents were replaced, but we did not obtain any evidence by cytological evaluation. One month later, ERCP and intraductal ultrasonography (IDUS) showed infiltrating growth of the tumor. Endoscopic ultrasonography guided fine-needle aspiration was performed at the same time, and pathological diagnosis was suggested as borderline IPMN. RESULTS: In the absence of pathological support, the patient presented with the clinical diagnosis of infiltrating intraductal papillary mucinous adenocarcinoma (IPMC) and was recommended for surgery. However, the patient and his family refused surgery, and were discharged. Subsequently, the patient died 6.5 months (197 days) following first diagnosis. CONCLUSIONS: Currently, the definition and classification of IPMN is done by specification, although there remain some difficulties in diagnosing its subtypes. For diagnostic purposes, CT, MRCP, ERCP, IDUS, EUS and EUS-FNA can all be applied. Cytological negative pathology might not completely rule out malignancy, and would still require further examination and follow-up. PMID- 26885136 TI - Treating patients with abdominal aortic aneurysm with endovascular repair and the crossover chimney technique in the internal iliac artery to protect the unilateral internal iliac artery. AB - This study aims to explore the treatment methods for patients with abdominal aortic aneurysms (AAAs) that required occlusion of the openings of the bilateral internal iliac arteries (IIAs) in endovascular aneurysm repair (EVAR) and to evaluate the efficacy of these treatments. Four patients with AAA were treated with endovascular aneurysm repair (EVAR) and the crossover chimney technique in the bilateral internal iliac arteries (IIAs). We inserted and released the abdominal aortic stent as usual and implanted the bypass stent graft simultaneously. The intraoperative immediate angiography showed complete isolation of the AAA and patency of the bypass. One month after surgery, it showed contrast engorgement in the bypass stent in three patients. The IIA on the bypass side and its branches had good developing. Another case in which we utilized a COOK stent, occlusion started at the opening of the bypass stent, with no occurrence of other complications. For patients in whom AAAs involve bilateral iliac arteries and the openings of the bilateral IIAs need to be occluded, EVAR and a crossover chimney technique can protect the unilateral IIA. PMID- 26885137 TI - Genetic characteristics of the couple with non-syndromic sensorineural hearing loss and fertility guidance. AB - PURPOSE: We aim to report a genetic testing and fertility guidance for the deaf through analyzing pedigree and molecular genetic characteristics of the couple who have non-syndromic sensorineural hearing loss (NSHL). METHODS: One of hospitalized congenial deaf couple and family members were included in this study. The wife was twin pregnant woman and her gestational age was 31(+5) pregnant weeks. The DNA was extracted from peripheral blood and umbilical vein blood, respectively. Mutation screening of common deafness genes was performed in pregnant women and other family members. Nine common mutations in four major deafness genes, GJB2 (35delG, 176del16, 235delC, 299delAT), GjB3 (C538T), SLC26A4 (IVS7-2A>G, A2168G) and Mitochondrial 12S rRNA (A1555G, C1494T), were detected simultaneously with a microarray based method. SLC26A4 whole genome sequencing was carried out for the results of the DNA microarray. According to the test results, the couple chose abortion termination of pregnancy twins, and after one year obtained singleton pregnancy by artificial insemination by donor (AID). In week 16 of pregnancy, amniocentesis had been done to collect fetal somatic cell and extract DNA, and then the above tests had been repeated. RESULTS: The couple had SLC26A4 combined heterozygous mutation. Both parents had SLC26A4 single heterozygous mutation. Twin fetuses had SLC26A4 combined heterozygous mutation. The probability of naturally being pregnant and bearing deaf children for the pregnant women was 100%. Fetus obtained by AID had SLC26A4 single heterozygous mutation. After the birth of the baby, her hearing has been normal. CONCLUSIONS: To reduce children with congenital deafness, screening high mutation sites by microarray, combined with pedigree analysis and gene sequencing is effective, and should be used as a routine inspection item for the deaf before marriage and pregnancy. On the basis of genetic testing for the couple with hearing loss, human assisted reproductive technology is a viable option to avoid the birth of infant with hereditary deafness. PMID- 26885138 TI - Central venous catheter malposition in the azygos vein and difficult endotracheal intubation in severe ankylosing spondylitis: a case report. AB - Ankylosing spondylitis (AS) can be challenging for anesthesiologists because central venous access can be difficult, and the airway can be blocked due to the fixed flexion deformity of the spine. In this case, we attempted central access via the right subclavian vein, but the catheter was repeatedly inserted into the azygos vein, which was confirmed by radiology. After several attempts, the catheter position was corrected at the superior vena cava-atrial junction. Although several useful devices have been developed to address difficult intubation, in this case, fiberoptic bronchoscopy was the only applicable safe alternative because of the patient's extremely severe chin on chest deformity and temporomandibular joint disease. We report a successful awake fiberoptic bronchoscopic intubation in a patient with extremely severe AS and recommend that the catheter placement should be confirmed with radiology to ensure proper positioning for severe AS patients. PMID- 26885140 TI - Breast metastasis of salivary duct carcinoma in a patient: a case report. AB - Salivary duct carcinoma (SDC) is a rare and highly aggressive cancer with a worse prognosis that has been demonstrated to exhibit invasive growth with early regional and distant metastasis. Breast metastasis of salivary duct carcinoma rarely occurs. Here, we reported a case of submandibular gland SDC metastasis to breast in a 64-year-old female patient who underwent a complete removal of a right submandibular gland and radical neck dissection in 2010 and undergo adjuvant radiotherapy and chemotherapy. Two years later, MRI identified mass in multiple regions, including bilateral cervical, bilateral breast, supraclavicular fossa, thyroid gland and the fourth thoracic vertebra. A fine-needle aspiration biopsy of the right breast was performed. SDC was confirmed by IHC analysis of the breast aspiration specimen. PMID- 26885139 TI - Nonsurgical treatment of 8 cases with esophageal perforations caused by ESD. AB - BACKGROUND: Esophageal perforation is a serious, but rare complication of high mortality following the endoscopic submucosal dissection (ESD) procedure. The aim of this study is to evaluate the efficacy and safety of nonsurgical treatment of esophageal perforations caused by ESD based on our clinical experience. METHODS: From January 2009 to November 2013, 8 patients were diagnosed with endoscopic perforation of the esophagus caused by ESD in our center. All cases were treated with nonsurgical measures, such as metallic clips, conservative treatment alone and therapeutic drainage. RESULTS: The places of perforation were closured by metallic clips immediately in 4 patients. Two patients were cured with conservative treatment alone. Therapeutic drainage with large-bore tube thoracostomy was applied in another 2 patients who had empyema following esophageal perforation. All of the patients were treated nonsurgically, and recovered well. CONCLUSION: Esophageal perforation caused by ESD can be detected and treated timely, and nonsurgical treatment seems to be a feasible and effective option for clinicians. PMID- 26885141 TI - Highly differentiated squamous cell carcinoma arising from a suprapubic cystostomy tract in a patient with transplanted kidney. AB - Squamous cell carcinoma arising from a suprapubic cystostomy tract (SCC-SCT) is a relatively rare bladder malignancy. We present a case of highly differentiated SCC-SCT involving the bladder in a 61-year-old patient with transplanted kidney. Abdominal magnetic resonance imaging revealed an anomalous mass (8 cm * 6 cm * 5 cm) surrounding the suprapubic cystostomy and a space-occupying lesion in the bladder. The pathology report revealed highly differentiated SCC. The patient received radiation therapy after he refused aggressive surgical management in 2012. There was no evidence of metastasis at his latest follow-up in early 2015. PMID- 26885142 TI - Pre-operative TNM staging of primary colorectal cancer by (18)F-FDG PET-CT or PET: a meta-analysis including 2283 patients. AB - The aim of the present study was to perform a meta-analysis to assess the diagnostic value of fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET-CT/PET in the pre-operative evaluation of TNM staging in patients with primary colorectal cancer (CRC). The Medline, Embase and Web of Knowledge were searched for studies assessing the diagnostic value of (18)F-FDG PET-CT/PET in the pre-operative evaluation of TNM staging in CRC patients. We pooled the sensitivity, specificity, positive and negative Likelihood ratio (LR+ and LR-) and Diagnostic Odds Ratio (DOR) and constructed summary receiver operating characteristic curves. A total of 28 studies including 2283 CRC patients were analyzed. The pre operative tumor detecting rate of PET-CT was 95.35%, which was superior to CT (P < 0.05). The pooled sensitivity and specificity of pre-operative T staging by PET CT/PET was 0.73 (95% CI: 0.65-0.81) and 0.99 (95% CI: 0.98-0.99), which the AUC and Q* were 0.96 and 0.91, respectively. Concerning pre-operative N staging, the pooled sensitivity and specificity of PET-CT/PET were 0.62 and 0.70, which the AUC and Q* were 0.76 and 0.70, respectively. As for M staging, the pooled sensitivity and specificity of PET-CT/PET were 0.91 (95% CI: 0.80-0.96) and 0.95 (95% CI: 0.91-0.98), which the AUC and Q* were 0.96 and 0.91, respectively. (18)F FDG PET-CT/PET had good performance in the pre-operative tumor detecting rate, T staging and M staging in patients with primary CRC, which might alter the therapeutic strategy. However, the diagnostic value of (18)F-FDG PET-CT/PET in pre-operative N staging in CRC patients was not ideal. PMID- 26885144 TI - Repair of acute injuries of the lateral ligament complex of the ankle by suture anchors. AB - OBJECTIVE: The objective of this study was to investigate the clinical curative effect of stage I repair of acute injuries of the lateral ligament complex of the ankle by the application of suture anchors. METHODS: We retrospectively analyzed 18 cases of III degree acute injuries of the lateral ligament complex of the ankle. RESULTS: There were statistically significant differences in preoperative and last follow-up VAS pain scores and AOFAS ankle hind-foot function scores. The X-ray talus displacement values in the anterior drawer test and pressure anteroposterior X-ray talar tilt in the ankle talar tilt test also showed statistically significant differences. Complications occurred in 2 patients, incision surface infection in one, and postoperative lateral dorsal skin numbness in one. All these cases were cured after symptomatic treatment. At the last follow-up all patients' ankle joint activity recovered to their preinjury function levels. CONCLUSION: The application of suture anchors for small incision stage I repair of the lateral collateral ligament of ankle joint degree III injury, can effectively restored the stability of ankle joint, and prevent the occurrence of chronic ankle instability complications. It is effective and feasible for the treatment of ankle joint lateral collateral ligament injuries. PMID- 26885143 TI - Direct clipping of a blister-like aneurysm in the supraclinoid segment of the internal carotid artery: a clinical analysis of nine cases. AB - To investigate the method and outcome from direct clipping of a blister-like aneurysm (BBA) of the internal carotid artery supraclinoid segment. This study featured nine BBA patients, including eight females and one male. The patients presented subarachnoid hemorrhage (SAH) as the initial symptom and were diagnosed with BBA in the supraclinoid segment through a vascular exam and imaging. During the exam, the internal carotid artery was pressed to block the blood flow, and a transcranial Doppler (TCD) was performed to examine the blood flow in the (BBA) ipsilateral middle cerebral artery. The results showed that the blood flow was reduced by less than 40% in all nine patients. During surgery, a pterional craniotomy was used to fully expose the aneurysm for clipping. While clipping the aneurysm, the arterial wall at the root of the aneurysm was also clipped to improve stability. Intraoperative ultrasonography was performed before and after clipping to examine the blood flow in the parent artery, middle cerebral artery and anterior cerebral artery. Moreover, a TCD was performed within one week after surgery to monitor intracranial blood flow. During BBA clipping, four patients exhibited stenosis of the parent artery, but intraoperative ultrasonography showed adequate blood flow in the anterior cerebral artery and middle cerebral artery. TCD was performed within one week after surgery to examine the blood flow in the middle cerebral artery on the operative side; the TCD showed adequate blood flow. The patients recovered well after surgery and were discharged. Digital subtraction angiography (DSA) or computed tomography angiography (CTA) was performed six to 12 months after the surgery and showed no aneurysm relapse. Moreover, six patients exhibited no stenosis of the parent artery, 20% stenosis was observed in one patient, 30% stenosis was observed in one patient, and 50% stenosis was observed in one patient; none of the patients showed clinical symptoms, and all patients exhibited good collateral circulation. Therefore, if a pre-operative TCD shows adequate compensatory contralateral blood flow in the (BBA) ipsilateral middle cerebral artery after the internal carotid artery is pressed to block the blood flow, then direct clipping of the BBA is a simple and feasible treatment strategy. However, when the aneurysm is clipped, the artery wall at the root of the aneurysm must also be clipped to improve stability. With adequate compensation, partial stenosis of the parent artery is acceptable. PMID- 26885145 TI - Intrahepatic biliary papillomatosis associated with malignant transformation: report of two cases and review of the literature. AB - Biliary papillomatosis (BP) is a rare disease characterized by multiple numerous papillary adenomas in both the intrahepatic and extrahepatic biliary tree. Due to its high recurrence rate and frequent transformation to malignancy, BP should not be considered a benign disease, and a radical resection with an adequate resection margin is advocated in cases of localized intrahepatic biliary papillomatosis. Since BP is a rare disease and its clinical features and outcomes are not well known, it's really difficult to diagnose the disease before operation. We encountered two cases diagnosed as intrahepatic biliary papillomatosis postoperatively, and herein present the diagnostic difficulties and therapeutic options for this rare disease. PMID- 26885146 TI - Severe hydrocephalus complicated with benign paroxysmal positional vertigo: one case report. AB - In this study, we reported one female patient diagnosed with severe hydrocephalus who presented with benign paroxysmal positional vertigo (BPPV). She presented with progressive headache and dizziness prior to hospitalization as chief complaints. She received Diagnostic Dix-Hallpike and Roll tests to make a definite diagnosis. The patient was cured after Gufoni maneuver and did not recur after 6-month follow-up. The diagnostic procedures of this female case prompted that prior to formal treatment, patients developing severe hydrocephalus complicated with BPPV should receive provocative test for positional dizziness, performed by experienced physicians from the Department of neurology and otolaryngology. PMID- 26885147 TI - Tumors and pseudotumors at the temporomandibular joint region in pediatric patients. AB - OBJECTIVE: To describe the clinical manifestations and types of, and our surgical experience with, neoplasms in the region of the temporomandibular joint (TMJ) in pediatric patients. MATERIALS AND METHODS: From September 1997 to December 2013, a total of 18 patients with neoplasms in the region of the TMJ were treated at our department. They all underwent open surgeries. The clinical manifestations and radiological aspects of all the patients were reviewed. The average follow-up period was 61.8 months with a range of 12-221 months. We reviewed the history, physical examination, images, and related radiological examinations. RESULTS: Of the 18 patients, 14 had benign tumors or pseudotumors, and four had malignant tumors. The ratio of pseudotumor to benign tumor to malignant tumor was 2.5:1:1. Limitations of mouth opening were more likely to occur with malignant tumors, and facial deformity had a higher incidence in benign tumors. Local resection was the first choice for patients with benign tumors or pseudotumors. All patients with malignant tumors underwent whole-tumor resection along the boundary, including the joint capsule, disc, and part of the temporal bone and mandible. During the follow-up period, no tumor reformation or new deformity was detected. CONCLUSIONS: In the diagnosis of masses in the TMJ region, CT and MRI play an important role. Surgical removal of the mass with/without joint attachment was sufficient to treat benign and malignant tumors. PMID- 26885148 TI - Stent-assisted mechanical recanalization for symptomatic subacute or chronic middle cerebral artery occlusion. AB - To assess the feasibility and short-term effects of treating patients with subacute or chronic middle cerebral artery (M1) occlusion by stent-assisted mechanical recanalization. Six patients with cerebral arteries occlusion underwent surgery. Six cerebral arteries occlusion in 5 patients were successfully recanalized. On postoperative day 1, four patients' symptoms were relieved and two patients' symptoms were exacerbated, of which one was significantly improved after 3 days, the other one's symptoms were recovered to preoperative levels in 2 weeks. No patients died after surgery. No stroke or transient ischemic attack occurred. The average follow-up of was 4.2 months, no worsening of condition, recurrence or death occurred. The results indicate that for patients with subacute or chronic middle cerebral artery (M1) occlusion, mechanical recanalization was technically feasible under the premise of strict case screening. Mechanical recanalization is able to improve ischemic symptoms and promote dysfunction restoration. But its long-term effect remains to be evaluated by further large samples, long-term follow-up studies. PMID- 26885149 TI - Pulmonary sequestration: a case report and literature review. AB - PURPOSE: Pulmonary sequestration (PS) is a rare congenital lung malformation. It is characterized by an abnormal mass of dysplastic lung tissue supplied by an anomalous systemic artery and separated from normal bronchopulmonary tree. Misdiagnosis and inadequate treatment can lead to recurrent pneumonia and fatal hemoptysis. METHODS: We report a 45 years female was diagnosed PS, and performed a brief review about the clinical features, diagnostic strategies, and management options of the PS. RESULTS: Her remarkable symptoms were cough and hemoptysis, the contrast- enhanced computed tomography of the chest revealed a multiloculated cystic solid mass filled with low density lesions and a feeding artery from the descending abdominal aorta to the cystic solid mass was visualized, then the patient suffered a right lower- lobe resection, and the surgery and pathological examination all supported the diagnosis of intralobar sequestration. CONCLUSIONS: Symptomatic patients of the pulmonary sequestration should be treated by surgery to avoid the risk of death due to massive hemoptysis. PMID- 26885150 TI - Parathyroid adenoma causing a spontaneous cervical and mediastinal massive hematoma. AB - Cervical and mediastinal hemorrhaging caused by a spontaneous rupture of a parathyroid adenoma has been rarely reported. Herein, we report a case of a 52 year-old woman who experienced a sudden onset of cervical and mediastinal bleeding related to a parathyroid adenoma. The patient had a history of trauma to the left thorax with a fracture of two ribs. Ultrasonography and computer tomography revealed a nodule in the retrotracheal space and hematoma of the bilateral trachea and thorax. Laboratory examinations revealed significant hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone. Surgery was performed and a dark-red, soft tumor was found behind the trachea, which adhered to the surrounding tissues. The pathological diagnosis was a parathyroid adenoma with hemosiderin deposition and fibrosis. PMID- 26885151 TI - Prostatic melioidosis rarely reported in China: two cases report and literatures review. AB - Melioidosis is a fatal, endemic disease caused by Burkholderiapseudomallei which is a gram-negative bacillus. Melioidosis present diversely that ranging from chronic disease to fulminant sepsis, and may affect almost any organ in the body. And in China, melioidosis presenting primarily as prostatic abscesses has rarely been reported. Rapid and accurate diagnostics are needed for melioidosis as the clinical presentation is nonspecific and treatment requires specific antibiotics. Here, we report the clinic features of two cases of prostatic melioidosis that we had cured during 1995 to 2015 and discuss its diagnosis and specific treatment. PMID- 26885152 TI - Post-neurosurgical meningitis caused by acinetobacter baumannii: case series and review of the literature. AB - BACKGROUND: Acinetobacter baumannii (A. baumannii), a gram-negative bacterium, has now become an important hospital pathogen, which causes various serious nosocomial infections worldwide. Bacterial meningitis is a common complication after neurosurgical operation, and the percentage of A. baumannii meningitis is growing, especially the one resisting multiple drugs. METHOD: We retrospectively reviewed the cases with postoperative A. baumannii meningitis (PABM) in the First Affiliated Hospital of Wenzhou Medical University from January 2013 to October 2014. And we retrieved the PubMed for cases with PABM and reviewed them. RESULT: Five cases were included in our retrospective study. Two cases with sensitive A. baumannii and one with multidrug-resistant acinetobacter baumannii (MRAB) were cured, and other two with MRAB died. CONCLUSION: Intraventricular or intrathecal colistin could be a treatment to the MRAB. PMID- 26885153 TI - Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling. AB - Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 MUM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V PI staining, while caspase3 activity was determined using an assay kit. Two dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway. PMID- 26885154 TI - Effects of two kinds of radio frequency ablations on morphology and function of left atrium in patients with atrial fibrillation. AB - OBJECTIVE: This study aims to observe the effects of circumferential pulmonary vein ablation (CPVA) and CPVA combined with complex fractionated atrial electro gram (CPVA+CFAE) on morphology and function of left atrium in patients with atrial fibrillation (AF). METHODS: To evaluate the effects of CPVA and CPVA+CFAE on morphology and function of left atrium, the left atrial volume and late diastolic velocity peak (Va) were determined by tissue Doppler imaging before and after CPVA and CPVA+CFAE, respectively. RESULTS: There was no statistical difference in the left atrial volume before and after CPVA. However, Va was significantly higher after CPVA (P=0.001). There was no statistical difference in both the left atrial volume and Va before and after CPVA+CFAE. Va after ablation was significantly higher in CPVA group than in CPVA+CFAE group (P=0.031). CONCLUSION: The left atrial function was significantly improved after CPVA, but CPVA+CFAE failed to markedly improve the left atrial function. This suggests that excessive atrial substrate ablation may damage the left atrial function. PMID- 26885155 TI - Clinical significance of urothelial carcinoma associated 1 in colon cancer. AB - This study aimed to investigate the expression levels of urothelial carcinoma associated 1 (UCA1) in cancer tissues and plasma of colon cancer patients, and evaluate its clinical significance. Quantitative real-time PCR was used to determine the expression levels of UCA1 in 80 pairs of colon cancer and adjacent normal tissues, plasma samples from 20 healthy controls, 20 colon cancer patients before and after tumor removal. The relationships between UCA1 expression and clinical features and overall survival were analyzed. Compared with adjacent normal tissues, UCA1 was significantly upregulated in colon cancer tissues, especially in cases with LNM and advanced TNM stages (P < 0.05). High UCA1 expression was associated with LMN, higher pT category, and advanced TNM stages (P < 0.05). Patients with high UCA1 expression had worse survival time than those with low UCA1 expression (adjusted HR = 2.002, 95% CI 1.007-3.981, P = 0.048). Furthermore, plasma levels of UCA1 in colon cancer patients were significantly higher than those of controls (P = 0.016). There was significant difference in plasma level of UCA1 between samples taken before and after surgery (P = 0.048). In conclusion, tissue expression of UCA1 is related to prognosis in colon cancer. Plasma UCA1 may serve as a potential biomarker for early diagnosis and disease monitoring of colon cancer patients. PMID- 26885156 TI - The anti-ulcerative colitis effects of Annona squamosa Linn. leaf aqueous extract in experimental animal model. AB - This study aimed to evaluate the anti-inflammatory effects of Annona squamosa (A. squamosa) leaf aqueous extract against acetic acid induced colitis in rats with a trial to explore its use for the treatment of colon inflammation. Sprague Dawley rats weighing 180-200 g were used in this study. Treatment with A. squamosa extract at dose 300 mg/kg for 4 weeks counteracted acetic acid induced ulcerative colitis by a significant decrease (P<0.05) of colonic tissue of malondialdehyde (MDA) and significant increases of catalase (CAT), glutathione (GSH) and glutathione peroxidase (Gpx) compared to ulcerative colitis control group. Furthermore, induction of oxidative stress was observed in the colonic tissue through the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) which significant increase in colonic tissue DNA by acetic acid. Moreover AA induced significant increase in serum interleukin-10 (IL10), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor (TGF 1beta), and C reactive protein (CRP) as compared to the control group. On the contrary, our results showed AA induced significant decrease of vascular endothelial growth factor (VEGF) and thyroid hormones triiodothyronin and thyroxin (T3 & T4) in installed group with AA as compared to control which significantly improved after treatment with A. squamosa leaf extract. Histopathological observation in our study confirmed the biochemical study. Thus, therapeutic method offer a sign to analyze further the effectiveness of A. squamosa as a unique agent for alleviating colitis. PMID- 26885157 TI - Is there any difference in survivorship of total hip arthroplasty with different bearing surfaces? A systematic review and network meta-analysis. AB - PURPOSE: Although many total hip bearing implants are widely used all over the world, simultaneous comparisons across the numerous available bearing surfaces are rare. The purpose of this study was to compare the survivorship of total hip arthroplasty (THA) with six available bearing implants. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) reporting survivorship or revision of ceramic-on-ceramic (CoC), ceramic-on-conventional polyethylene (CoPc), ceramic-on-highly-crosslinked polyethylene (CoPxl), metal-on-conventional polyethylene (MoPc), metal-on-highly-crosslinked polyethylene (MoPxl), or metal on-metal (MoM) bearing implants. The synthesis of present evidence was performed by both the traditional direct-comparison meta-analysis and network meta analysis. RESULTS: In total, 40 RCTs involving a total of 5321 THAs were identified. The pooled data of network meta-analysis showed no difference in relative risk (RR) of revision across CoC, CoPc, CoPxl and MoPxl bearings. However, the MoM bearing was demonstrated with a significant higher risk of revision compared with CoC (RR 5.10; 95% CI=1.62 to 16.81), CoPc (RR 4.80; 95% CI=1.29 to 17.09), or MoPxl (RR 3.85; 95% CI=1.16 to 14.29), and the MoPc bearing was indicated with a higher risk of revision compared with CoC (RR 2.83; 95% CI=1.20 to 6.63). The ranking probabilities of the effective interventions also revealed the inferiority of the MoM and MoPc implants in survivorship (both 0%, 95% CI=0% to 0%) compared with CoC (39%, 95% CI=0% to 100%), CoPc (33%, 95% CI=0% to 100%), CoPxl (7%, 95% CI=0% to 100%) or MoPxl (21%, 95% CI=0% to 100%). CONCLUSIONS: The present evidence indicated the similar performance in survivorship among CoC, CoPc, CoPxl and MoPxl bearing implants, and that all likely have superiority compared with the MoM and MoPc bearing implants in THA procedures. Long-term RCT data are required to confirm these conclusions and better inform clinical decisions. PMID- 26885158 TI - Association of transforming growth factor-beta1 polymorphisms with the risk of diabetes mellitus. AB - The association between transforming growth factor-beta1 (TGF-beta1) polymorphisms with the risk of diabetes mellitus (DM) remains elusive. We aimed to evaluate the relationship between TGF-beta1 polymorphisms and DM risk. We searched the association studies according to a predefined criteria using electronic databases. The strength of association between TGF-beta1 codon 10/25 polymorphisms and the risk of DM was evaluated by odds ratio (OR) with the corresponding 95% confidence interval (CI). Six case-control studies were identified for the analysis of the association between TGF-beta1 codon 10/25 polymorphism and the risk of DM. CC genotype at the codon 10 polymorphism was associated with the risk of type 2 DM (T2DM) (P = 0.026, OR = 1.397, 95% CI = 1.041-1.874). No marked association was observed between codon 25 polymorphism and the risk of DM. No evidence of marked publication bias was observed. CC genotype at the TGF-beta1 codon 10 site may be an indicator for the risk of T2DM. However, further larger studies should be performed in the future. PMID- 26885159 TI - Tooth loss and risk of oral squamous cell carcinoma in Chinese Han population. AB - OBJECTIVE: Association between tooth loss and oral cancer risk was investigated primary studies and meta-analyses, however, the results remain inconsistent. This study is to test the association between tooth loss and oral squamous cell carcinoma (OSCC) in Chinese Han population. METHODS: Case-control study including histologically confirmed OSCC cases and healthy controls individually matched to the cases for age, sex, and district of residence between May 1, 2010, and Match 31, 2014. Univariate and multiple logistic regression models were used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using the STATA 12.0 software. RESULTS: Finally included 150 OSCC patients and 167 healthy controls. Cases had a significantly higher mean (SD) number of lost teeth than controls (10.03+/-6.62 vs. 8.69+/-5.20; P = 0.045). The results of univariate analysis and adjustment for smoking and alcohol showed a non significant association between tooth loss and OSCC. After adjustment for age at diagnosis, gender, smoking, alcohol use, body mass index, and history of diabetes mellitus, those in the upper tertiles of lost tooth were significantly more likely to have OSCC (OR = 3.64, 95% CI = 1.15-11.53, P = 0.03; P for trend = 0.11) than in the lower tertiles. The unadjusted and adjusted results of per teeth also revealed non-significant association. CONCLUSIONS: Tooth loss may be not associated with risk of oral cancer in this case-control study. The relevant large-scale studies in Chinese are suggested to perform. PMID- 26885160 TI - Application of flash dual-source CT at low radiation dose and low contrast medium dose in triple-rule-out (tro) examination. AB - OBJECTIVE: To evaluate the clinical imaging capacity of FLASH dual-source CT at low radiation dose and low contrast medium dose in thoracic aorta, pulmonary artery & vein and coronary artery. METHOD: One hundred and eight patients of thoracalgia were randomly divided into two groups; 60 cases (group A) received dual-source CT scan in flash model at 100 KV and contrast medium dose of 74 ml combined with digital subtraction angiography (DSA) examination; 48 cases (group B) received retrospectively. ECG-triggered high-pitch spiral acquisition at 120 KV and contrast medium dose of 101 ml. Several image reconstruction techniques were adopted for coronary artery, pulmonary artery and aorta. The imaging quality and the diagnostic value of this technique were evaluated. Coronary artery stenosis of group A was compared against the results of DSA examination. RESULTS: The scan time in group A was obviously shorter than that of group B, i.e., t=0.7+/-0.1 s in group A and t=7.7+/-1.7 s in group A. The image reconstruction phase of coronary artery was 70.4+/-15.6% in group A, and the systolic phase accounted for 13.3% of the optimal reconstruction phase. Compared with group B, the radiation dose of group A decreased obviously, i.e. ED=2.7+/-0.7 mSv for group A and ED=21.6+/-6.0 mSv for group B. Moreover, less contrast agent was consumed in group A than in group B, which was 74 ml in group A and 101 ml in group B. The image quality of aorta and pulmonary artery & vein was grade 1 for all cases in group A, which was the same as with group B. The coronary artery images of group A had better quality, with score of 2.9+/-0.1. Of 780 segments, only 2 segments could be effectively diagnosed, showing no statistically significant differences from group B (P>0.05). The coronary artery stenosis revealed by dual-source CT for group A was not significantly different from that by DSA (P>0.05). CONCLUSION: FLASH dual-source CT scan at reduced radiation dose and reduced contrast medium dose used for triple-rule-out (TRO) examination achieved good image quality and clear visualization of blood vessels. Moreover, this CT scan technique is fast and rapid in diagnosis and suitable for extensive clinical settings. PMID- 26885161 TI - Clinical features and pathophysiology of belching disorders. AB - The symptomatic characteristics and psychosocial factors of belching were analyzed through questionnaire, and the pathophysiology of belch was studied with the combined methods of high-resolution manometry and impedance (HRM-IMP). 21 consecutively-enrolled patients with repeated belching, were conducted a questionnaire survey, and the data were analyzed with Pearson correlation analysis and exact propability method. 10 patients were performed HRM-IMP. 20 patients met the diagnostic criteria of belch, among who 17 cases had overlapped symptoms, and the functional dyspepsia was the most common, followed by gastroesophageal reflux disease; 16 patients experienced mental stimulation or negative events; 12 cases existed anxiety and (or) depression; 8 cases had neurotic personality. The number of the overlapped symptoms was associated with the anxiety status, while the belch severity had nothing to do with the anxiety/depression status. Among the 10 patients who accepted HRM-IMP, 9 existed the esophageal motility dysfunction, and 9 had supra-gastric belching. Belch had a variety of clinical manifestations, related to the mood changes and the environmental stress, and normally was combined with the abnormalities of psychology and personality traits. The belch patients normally experienced the esophageal motility disorders, among which the typical pattern was supra-gastric belching. PMID- 26885162 TI - Analysis of the risk factors for the short-term prognosis of acute ischemic stroke. AB - This study investigated the risk factors for the short-term prognosis of acute ischemic stroke to provide a scientific evidence for improving prevention and treatment. A total of 2557 cases of acute ischemic stroke were included in the study. We collected the data on demographic characteristics, life style-related risk factors, clinical feature, and other clinical characteristics for all the participants. The outcomes were assessed using the modified Rankin scale (mRs) on day 14 or at discharge. According to the mRs score, the subjects were divided into three groups, namely, the control group (0<= mRs <=2), the disability group (3<= mRs <=5), and the death group (mRs = 6). The general conditions of these three groups were compared. An mRs score of 3<= mRs <=6 belonged to the composite outcome group. Logistic regression was also applied to analyze the risk factors of short-term prognosis. Monovariant logistic regression showed that age, on-set admission, hospital stays, temperature, heart rate, stroke subtype, hypertension, hyperglycemia, history of heart disease, history of atrial fibrillation, history of cerebral stroke, drinking, count of WBC, count of mononuclear leucocyte, and rate of neutrophile granulocyte were statically significant. To further control the confounding factors, multivariant logistic regression analysis was carried out. The result showed that age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were related to the short-term prognosis. Age, on-set admission, hospital stays, temperature, heart rate, hyperglycemia, history of atrial fibrillation, and cerebral stroke history were the risk factors of the short-term prognosis of acute ischemic stroke. PMID- 26885163 TI - Therapeutic effects of cytoprotective agent on breast reconstruction after breast cancer surgery. AB - Most patients will choose breast reconstruction after breast cancer surgery, while radiotherapy will damage skin and soft tissue so that will have adverse effect on reconstruction. In this study, we assume that the usage of Amifostine can reduce the incidence of complications after breast reconstruction so that provides more choices of reconstruction operation. Dividing SD rats into surgical placement expansion material group (include 15 ml normal saline) and simple operation group. Then further divide the former into non intervention group , radiation group and Radiation therapy combined with Amie amifostine treatment group. The decubation is 45 days after operation. Macroscopic evaluate the complications of skin and soft tissue by ImageJ. There is no obvious complications of skin and soft tissue for control group, radiotherapy alone group and radiotherapy with application of Amifostine group by macroscopic evaluation. The animals that are in expanded object group, damage probability of skin and soft tissue when use Amifostine is lower than that of radiotherapy alone group (30% vs. 69%, P=0.041). ImageJ shows the necrosis probability of skin and soft tissue when use Amifostine is obvious lower than radiotherapy alone group (6.96% vs. 12.94%, P=0.019). In conclusion, prevention and treatment of Amifostine can significantly reduce the complications of skin and soft tissue which is helpful to breast reconstruction after breast cancer surgery. PMID- 26885164 TI - Carotid atherosclerosis is associated with hypertension in a hospital-based retrospective cohort. AB - OBJECTIVE: We aim to investigate the association between carotid artery plaque and blood pressure variation, as well as other cardiovascular risk factors. MATERIALS AND METHODS: We retrospectively analyzed clinical data of inpatients with high blood pressure treated in the Department of Hypertension from April 2009 to June 2010. Results from carotid ultrasonography, demographic characteristics, and other clinical data were obtained from 408 patients. RESULTS: (1) The rate of positive plaque in carotid artery was 55.1%, and there was no difference between men and women. However, this rate was positively correlated with the age of the patients. (2) The rate of positive plaque in carotid artery was associated with the duration of the disease, fasting blood glucose levels, total cholesterol, and low-density lipoprotein-cholesterol (LDL C). (3) The prevalence of carotid artery plaque increased in accordance with the coefficient of systolic pressure variation (X(2) = 15.83, P = 0.001), whereas no correlation existed between prevalence of carotid artery plaque and coefficient of diastolic pressure variation and the plaque prevalence (X(2) = 0.24, P = 0.97). Mean systolic blood pressure (MSBP) was positively correlated with prevalence of carotid artery plaque (X(2) = 10.47, P = 0.005). (4) Multivariate regression analysis indicated that carotid plaque was associated with the age, duration of hypertension, high-density lipoprotein-cholesterol (HDL-C), LDL-C, 24 h MSBP, and coefficient of systolic pressure variation, whereas no associations were found with the coefficient of diastolic pressure variation, 24 h average diastolic blood pressure (AvDP), and 24 h mean arterial pressure (MAP) (P > 0.05). CONCLUSION: Carotid atherosclerosis was independently associated with variation of blood pressure, especially with coefficient of systolic blood pressure variation. PMID- 26885165 TI - Selectively predictive calcium supplementation using NCCN risk stratification system after thyroidectomy with differentiated thyroid cancer. AB - BACKGROUND: Hypocalcemia is a common complication following thyroidectomy. To explore reasonable and simple methods for predicting postoperative hypocalcemia and identify the optimal strategies for selective calcium supplement are meaningful for surgeon. METHODS: Based on the NCCN risk stratification system, patients were divided into 4 groups (A-D): low-risk group A, who only underwent limited thyroidectomy (LT) and high-risk groups B, C and D, who had received total thyroidectomy (TT) and selective central and/or lateral neck dissection (SND). After surgery, group C patients were orally given calcium gluconate and group D patients were intravenously given calcium 2 g/day for 7 days, while group B patients did not receive any calcium supplement. Serum calcium and parathyroid hormone (PTH) levels were collected before and after surgery. The incidence of asymptomatic and symptomatic hypocalcemia in each group was recorded. RESULTS: A total of 132 patients with differentiated thyroid carcinoma (DTC) were included who received surgical treatment. No a significant change was observed in serum calcium and PTH levels in group A, while significant decreases in serum calcium and PTH levels were seen in group B (P < 0.05). Intravenous calcium supplement in group D resulted in a more rapid recovery in serum calcium levels (P < 0.05). The incidences of symptomatic hypocalcemia and asymptomatic hypocalcemia were significantly lower in group A and group D respectively compared to the other groups (All P values < 0.05). In group B, a highest asymptomatic and symptomatic hypocalcemia incidence was detected. CONCLUSION: Selective calcium supplementation for DTC based on NCCN risk stratification system could be recommended for the high-risk patients. PMID- 26885166 TI - Effects of brain-derived neurotrophic factor-pretreated neuron stem cell transplantation on Alzheimer's disease model mice. AB - Alzheimer's disease (AD) is a common case of dementia and its possible therapies, such as neuron stem cell (NSC) transplantation therapy, have been studied for years. In order to improve NSC transplantation effects, we were inspired to pretreat NSC using brain-derived neurotrophic factor (BDNF) before transplantation. The AD mouse model was constructed and effects of BDNF+NSC transplant group and traditional NSC transplant group were compared using the four indicators: conditions of learning and memory ability recovery tested by Morris Water Maze (MWM), number of basal forebrain cholinergic neurons, expression of synaptophysin, and number of acetylcholinesterase (ACHE)-positive fibers detected by chemical staining. Results showed all the four indicators were significantly lower in the AD model group than the control group (P < 0.05). Traditional NSC transplantation could improve these indicators to some extent but still possessed significant differences from the control group (P < 0.05). Especially, the BDNF+NSC transplant group showed significant improvements in the four indicators when compared with the AD model group (P < 0.05). Taken these data together, BDNF pretreatment improved the NSC transplantation effects, showing advantages over the traditional NSC transplantation. Our study could facilitate the application of stem cell transplantation therapy to AD treatment. PMID- 26885167 TI - Up-regulation of ICAM-1mRNA and IL-1betamRNA in lung tissues of a rat model of COPD. AB - Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by airflow obstruction that is usually progressive and not fully reversible. It is accompanied by the abnormal inflammatory response of lung to toxic particles or gas. Studies indicate that chronic inflammatory injuries of airway, pulmonary parenchyma and pulmonary vessels are the characteristic changes of COPD. Adhesion of inflammatory cells is the important link of pulmonary infection. Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein involved in binding with mediated cells or with the extracellular matrix in the process called cell adhesion. IL-1beta is an important inflammatory mediator as well as the promoter and critical inducer of cytokine cascade reaction. In this study, the rat model of COPD was established by smoking + intratracheal instillation of LPS (the experimental group). PaO2 and PaCO2 were measured. ICAM-1mRNA and IL 1betamRNA level in lung homogenate were detected by immunohistochemistry and RT PCR and were compared with those of the rats treated by smoke exposure (the control group) and the healthy rats (the blank group) in order to investigate the effect of ICAM-1 and IL-1beta in lung injury of COPD. This study showed that the respiratory function of rats with COPD was decreased. PaO2 of rats in the experimental group, the control group and the blank group decreased successively, and the comparison between any two groups had significant difference. PaCO2 increased successively, and the comparison between any two groups had significant difference. Immunohistochemistry results showed that protein expression of ICAM-1 and IL-1beta in lung tissues of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. RT-PCR results showed that ICAM-1mRNA and IL 1betamRNA level of rats in the experimental group was higher than that in the control group and the blank group, and the comparison between any two groups had significant difference. This study indicated that the decreased respiratory function of rats with COPD was associated with the imbalance of inflammatory cascade and the up-regulation of ICAM-1mRNA and IL-1betamRNA in lung tissues and cells caused inflammatory injury and decreased respiratory function. PMID- 26885168 TI - Roles of mycobacterium tuberculosis ESAT-6 in the development of renal injury. AB - OBJECTIVE: The present study was designed to evaluate the role of mycobacterium tuberculosis early secretory antigen target-6 (MtbESAT-6) in the development of renal injury. METHODS: PET42a (+) ESAT6 prokaryotic expression plasmid was constructed and the purified ESAT6 protein without endotoxin was obtained. Sixty healthy, clean, male Kunming mice were randomly divided into two groups: the experimental group (n = 30) and the control group (n = 30). Each mouse in the experimental group were injected with 0.5 ml ESAT-6 protein, and each mouse in the control group were injected with 0.5 ml sterile saline on the tail vein. Blood, urine and kidney tissues were collected. Serum creatinine (Scr), blood urea nitrogen (BUN), and urinary creatinine (Cr) were determined by HITACHI 7150 automatic biochemical analyzer and creatinine clearance rate (Ccr) was calculated. Renal tissues were conducted for hematoxylin-eosin (HE) staining and pathological scores of renal injury were recorded under the light microscope. RESULTS: Using MTB H37Ra strains genome DNA as template, the ESAT6 gene amplified by Hieff Pfu DNA Polymerase using polymerase chain reaction (PCR) technique was consistent with the expected size. PET42a (+) ESAT6 vector plasmid was successfully obtained and ESAT6 recombinant protein was successfully expressed with the protein concentration of 1.69 mg/ml. BUN and Scr in the experimental group were gradually increased, Ccr was gradually decreased, and the pathological score of renal injury increased gradually, and all of which were significantly higher than that in the control group after the experiment of 12 h, 24 h and 48 h (all P < 0.05). CONCLUSION: MtbESAT-6 might contribute to the development of renal injury. PMID- 26885169 TI - Snare sheath versus evolution sheath in transvenous lead extraction. AB - Lead extraction remains a challenging procedure with significant success. Owing to the increasing use of cardiac implantable electronic devices, there is a growing need for effective techniques management, to avoid the occurrence of device-related complications and lead dysfunction. We made a comparison of Evolution sheath and Needles Eye Snare sheath (abbreviated to Snare sheath) by analyzed the results using two kind of the methods in the Cardiology Center of Peking University People's Hospital. In the retrospective study we evaluated patients who underwent lead extraction from July 2013 to July 2014. Those who underwent lead removal without using evolution or snare were excluded. Primary endpoints included total exposure time, operation time, and complications. Data on clinical characteristics, indications, and outcomes were prospectively collected and analyzed. A total of 76 patients were included in the study (65.8% male; aged 68.1+/-14.34 years old). Snare and Evolution were used in 59 and 17 patients, respectively. A total of 134 leads were removed with 103 leads (76.87%) extracted using the Snare sheath. Lead age was 10.8+/-7.0 years. Complete extraction was observed in 67 patients of 124 leads. Evolution sheath was associated with significantly lower complication even after adjustment of the number of leads, type of leads, and lead age, compared to the Snare group (P<0.05). In the Snare sheath group, mortality rate was 1.69% and minor complication rate was 3.39%. When compared to the Snare sheath, lead extraction with the Evolution sheath has less X-ray exposure time and less operation time (P<0.05), while with a higher success rate (P<0.05). Besides, the Evolution group has fewer major and minor complications. PMID- 26885170 TI - Immunohistochemical characterisation of molecular subtypes in endometrial cancer. AB - Four molecular subtypes have lately been established in endometrial cancer basing on estrogen receptor (ER), progesterone receptor (PR) and HER2 status: ER+/PR+/HER2+, ER+/PR+/HER2-, ER-/PR-/HER2+ and ER-/PR-/HER2-. The subtypes have shown diversity in terms of prognosis, clinicopathological and molecular characteristics, with ER+/PR+/HER2- and ER-/PR-/HER2+ group exhibiting exceptionally benign and aggressive behavior, respectively. We have further characterized the subtypes in the context of pathways known to drive endometrial carcinogenesis: phosphatidylinositol 3-kinase (PI3K)-AKT pathway (ERBB/PI3K pathway), TP53 system, and the mismatch repair (MMR) mechanism. Analysis of tumor heterogeneity was also included. ER+/PR+/HER2+ was characterized by active ERBB/PI3K pathway occurring in 58% of cases. Subtype ER-/PR-/HER2+ was characterized by the most frequent TP53 mutations (83% of cases). Triple negative phenotype utterly lacked active ERBB/PI3K pathway. Analyzed major pathways rarely correlated with clinicopathologial data but mutated TP53 and retained MMR did correlate with shorter overall survival (both P<0.01). The presence of tumor heterogeneity was most frequent in ER-/PR-/HER2+ subtype (53% of all cases). The presented results further emphasize that the molecular subtype distinction, along with MMR and TP53 status, could be a useful diagnostic tool in guiding individualized therapy. PMID- 26885171 TI - Cognitive impairments associated with corpus callosum infarction: a ten cases study. AB - The aim of this study was to determine whether the cognitive impairment is associated with corpus callosum infarctions. Ten corpus callosum infarction patients were enrolled in this study. Their emotions, cognitive and language abilities, memory, comprehensive perception were assessed using the Chinese version of following measures: Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT), Wechsler Adult Intelligence Scale (WAIS) Digit Span subtest and so on. The same measurements were performed on healthy control participants as contrast for analysis. Infarction most frequently occurred in the body and/or splenium of the corpus callosum. The scores of the most cognitive tests in the corpus callosum infarction patients were significantly worse than those of the control participants (P<0.05). Except for the naming ability, the patients showed significantly poorer performance at the overall level of MMSE than the controls did (P<0.05). Consistently, the results of MoCA suggested a significant reduction in visuospatial abilities of execution, orientation, attention, calculation, delayed memory, language, and repetition capabilities in the patients with respect to the control (P<0.05). In addition, the scores in the case group were significantly worse than those in the control group in the auditory word learning test, digital span and Rey complex figure test (P<0.05). Corpus callosum infarction can cause cognitive dysfunction, which poses obstacles to memory in the acute phase, accompanied by different degrees of decline in visuospatial abilities, attention and calculating abilities. PMID- 26885173 TI - TLR2 expression doesn't change in ox-LDL mediated inflammation in Human umbilical vein endothelial cells under high glucose culture. AB - BACKGROUND: Inflammatory responses induced by ox-LDL play important roles in atherogenesis, and could be promoted in diabetic patients. Toll-like receptor (TLR)2 is an innate inflammatory receptor, and is enhanced in human umbilical vein endothelial cells (HUVECs) under high glucose conditions. Ox-LDL-TLR2 pathway activation and further inflammation in monocytes are involved in the atherosclerosis formation. OBJECTIVE: What role of TLR2 plays on ox-LDL-induced inflammation in HUVECs remains unclear, especially in high glucose conditions. The purpose of this study is to explore the effect and role of ox-LDL-TLR2 pathway on the inflammatory responses in HUVECs. METHODS: 1 hour prior to the treatment, HUVECs were treated with or without neutralizing anti-TLR2 antibody. After that, HUVECs were treated with ox-LDL (20, or 40 MUg/ml) or LPS (200 ng/ml) under normal and high glucose conditions. The expressions of ICAM-1 and TLR2 protein were analyzed by immunoblotting, and IL-6 and IL-8 were measured by ELISA. RESULTS: Compared with those in normal glucose condition, IL-6 and IL-8 expression were increased in high glucose condition. The stimulation of ox-LDL and LPS both increased the expression of ICAM-1, IL-6 and IL-8, but did not change TLR2 protein expression in both normal and high glucose conditions. Additionally, the expression of ICAM-1, IL-6 and IL-8 was not changed when TLR2 was knocked out under these two conditions. CONCLUSION: The inflammatory responses induced by Ox-LDL were not changed with or without TLR2 under both normal and high glucose conditions in HUVECs. Our study indicates TLR2 is not involved in the ox-LDL mediated endothelial injury under high glucose conditions, which is an important step of atherosclerosis formation in diabetes. PMID- 26885172 TI - A case of kidney transplantation using donation after circulatory death with renal calculi. AB - Donation after circulatory death (DCD) supplies a big percentage of the organ source pool. Compared to living-related donations, donor kidneys from DCD are commonly with lower quality since they inevitably suffer from hypoxia, hypotension, and inadequate organ perfusion during the progression to circulatory arrest. The current case presents a 44-year-old male donor with wide range subarachnoid hemorrhage and multiple skull fracture from a car accident. Multiple stones were detected in his right kidney. We performed a modified ex vivo pyelolithotomy and ureteroscopy on the bench to render a stone-free allograft. We also improved the donor kidney with hypothermic/perfusion preservation machine before renal transplantation. The recipient showed no complications during the first two-month post-operational follow-up. Such a donor kidney with stones may probably be discarded by conventional perspective. Yet, the combination of the ex vivo bench-surgery technique and hypothermic oxygenation/perfusion makes it a qualified donor kidney. Thus we have demonstrated a promising way of saving borderline qualified DCD donor kidneys. PMID- 26885174 TI - Intrapleural administration of DNase alone for pleural empyema. AB - INTRODUCTION: Pleural empyema is a severe complication of various diseases. The essential is the inserting a drain into the pleural cavity and evacuation of the pus. Sometimes the pus is very thick and its evacuation and re-expansion of the lung is very difficult. METHODS: We report a group of 10 patients with intrapleural administration of Pulmozyme (dornase alpha) in dosages of either 2.5 mg once or on two separate occasions. All of the patients had a chest tube inserted into the pleural cavity. Measurement of viscosity was done before and after the instillation of the dornase alpha. RESULTS: In six patients dornase alfa was introduced into the pleural cavity once. Three of them received this on the 4th whilst the rest were treated with the agent on the 6th day. Four patients received the dornase alpha twice because of the small amount of drainage fluid after the previous instillation. Five patients were discharged from hospital with complete re-expansion of their lungs. Two patients were qualified for a surgical operation since the lung was trapped and did not re-expand. Three patients had to be discharged with a drain as a result of incomplete re-expansion of the lung. In all the patients the density of the pus after administering the dornase alpha decreased and the amount of the pus drainage increased. CONCLUSIONS: Dornase alpha may be used in some patients with pleural empyema with good results. PMID- 26885175 TI - The causes of lower-extremity deep venous thrombosis in the children with cranial diseases. AB - In order to investigate the prevalence of lower-extremity deep venous thrombosis (DVT) and to explore its possible reasons in children patients who received neurosurgery operation. Clinical data of 4958 cases children patients with lower extremity DVT and without the thrombosis after the neurosurgery operation from 2010 January to 2014 December in department of neurosurgery of Tian Tan hospital were collected and analyzed. 18 cases children were diagnosed with lower extremity DVT. All of them had invasive operation of lower-extremity deep venous catheterization. The mainly primary diseases of thrombosis children were craniopharyngioma. They have longer operation time compared with those without thrombosis (P<0.05). Therefore, the causes of DVT in neurosurgical children involve not only deep venous catheter-related but also neurological primary disease and operation time. PMID- 26885177 TI - Better plans and more powerful evidence are needed in the research and treatment of chronic hepatitis B in China. AB - China has the first largest global pool of chronic hepatitis B (CHB) infection. With the implementation of comprehensive intervention of neonatal vaccination based on national strategy, some achievements have been made in control of hepatitis B in China. However, some problems remain unresolved in the research field as well as management of CHB. Currently, empirical therapy, poor study design, inefficient management, low compliance rate of patients, lack of public awareness and economic factor hampers the research and treatment of CHB in China. We propose that China should take more effective measures to improve the study quality, social management, the relief of economic burden for the needed patients, public awareness, evidence-based policies and medicine, supervision for clinical practice, diagnostics ability and laboratory quality, the compliance of patients, and the quality of Traditional Chinese Medicine (TCM) in the management of CHB infection in the future. PMID- 26885178 TI - Endometrial stem cells: clinical application and pathological roles. AB - Adult stem cells occur in human endometrium. Menstrual-blood derived stem cells (MenSCs) are mesenchymal stem cells that can be obtained in a non-invasive manner. Due to their rapid proliferation rate, low immunogenicity, and low tumorigenicity, MenSCs are used extensively in tissue engineering. They can be induced into multiple cell lineages under certain conditions. MenSCs contribute to tissue repair via several different mechanisms, highlighting their great promise in clinical applications. Endometrial stem cells may also be used to shed light on the pathogenesis of endometriosis and endometrial carcinoma. This review will cover recent progress in this field. PMID- 26885179 TI - On the preparation of transferrin modified artesunate nanoliposomes and their glioma-targeting treatment in-vitro and in-vivo. AB - OBJECTIVE: To prepare transferrin modified artesunate nanoliposomes (Tf-ART-LPs) and study their glioma U87 cells-targeting treatment in-vitro and in-vivo. METHODS: Ammonium sulfate transmembrane gradient method was used to prepare Tf ART-LPs, whose size and stability was detected by a Nanosizer. Besides, the encapsulation efficiency and release rate of artesunate (ART) were tested by a ultraviolet spectrophotometer. Further, isothiocyanate (FITC) was used to label nanoliposomes and the cell-targeting property of Tf-ART-LP in-vitro was observed under a fluorescence microscope. In addition, CCK-8 method was used to detect the effect of single nanoliposomes and Tf-ART-LPs on the viability of glioma U87 cells. At last, a subcutaneously implanted tumor model in nude mouse was established for studying the in-vivo anti-tumor effect of Tf-ART-LPs by caudal vein injection. The tumor volume and mice weight were monitored and pathological sections of their major organs were analyzed. RESULTS: Tf-ART-LPs were spherical with an average diameter of 94.2 nm. They showed no aggregation after being stored in a refrigerator for 14 days at 4 degrees C. The encapsulation efficiency and highest releasing rate (48 hours after being placed in normal saline under 37 degrees C) of ART was 85.9% and 58.7+/-2.9%, respectively. The uptake rate of U87 cells was 59.8+/-3.8% for Tf-ART-LPs and only 18.7+/-4.5% for ART-LPs. While single liposomes almost showed no toxicity, Tf-ART-LP had a concentration dependent killing effect on U87 cells. Within 32 days of treatment, the growth of U87 cells was well inhibited by Tf-ART-LPs without significant toxicity. CONCLUSION: In this study, transferrin modified artesunate liposomes we prepared have a good targeting property to glioma U87 cells and good effect on glioma both in-vitro and in-vivo. PMID- 26885176 TI - Role of autophagy in chronic kidney diseases. AB - Chronic kidney diseases (CKD), a common pathway of various glomerular diseases, which carries great morbidity and mortality to people. CKD is characterized by progressive kidney fibrosis and remodeling. CKD is also associated with the depletion of glomerular and tubular cells. Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. It plays an important role in both normal and disease states, including immunity, inflammation, and adaptation to stress. Evidence has indicated that impaired autophagic activity is involved in the development of CKD. Here, we review the progress in our understanding of the role of autophagy in the development and progression of CKD. Targeting the autophagic signaling pathways may be a therapeutic strategy for CKD. PMID- 26885180 TI - Construction and identification of multiple genes Co silence of plasmid shRNA. AB - Objective To construct and identify the eukaryotic vector expressing shRNA (Plasmid-1), which expressed the VEGF, C-myc, Survivin and hTERT gene at the same time. To detect its interference effects on the nasopharyngeal carcinoma cell line (CNE-2Z) compared with single gene plasmid VEFG (Plasmid-2). Methods According to the sequence of VEGF, C-myc, Survivin and hTERT gene, we designed 2 oligonucleotide sequences and synthesized a complementary DNA chain, then inserted it into the eukaryotic vector expressing pGenesil 1. The cell proliferation activity was detected by MTT method. The interference efficacy on human nasopharyngeal carcinoma cell line (CNE-2Z) in the level of mRNA and protein were detected by RT-PCR and Western-bolt. The inhibitory effect of plasmid on tumor in nude mice was also observed in vivo. Results The restriction enzyme digestion and sequencing technologies confirmed the construction of recombinant eukaryotic vector expressing was correct. The plasmid was transfected into CNE-2Z cells, green fluorescence can be seen clearly in the single gene and multi gene transfected cells under fluorescent microscope. MTT showed that the proliferation of cell was inhibited, the invasive ability was decreased in vitro, and the inhibition effects of single gene plasmid on the growth and proliferation of cells were lower than multi gene. Real-time-PCR and Western-bolt confirmed that the expression of target gene was decreased in the level of mRNA and protein, and the interference effect of multi gene was better than the single gene. The nude mice experiment showed that the interference effect of shRNA plasmid on the growth of tumor cell was better than single gene plasmid Conclusion We constructed a shRNA plasmid encoded four different genes successfully. After transfected with nasopharyngeal carcinoma cells, it can interfere the expression of VEGF, C-myc, Survivin and hTERT gene at the same time. And the interference effect was better than silence VEGF alone. Out results may provide experimental basis for multi gene therapy in the treatment of nasopharyngeal carcinoma. PMID- 26885181 TI - Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat. AB - Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-alpha, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol. PMID- 26885182 TI - Clinical and prognostic significance of HIF-1alpha in glioma patients: a meta analysis. AB - Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1alpha) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1alpha expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I(2)<50%, P>0.01). Overall, our results showed that HIF-1alpha expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1alpha expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1alpha expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1alpha expression was associated with high grade of glioma and OS, indicating that HIF-1alpha could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research. PMID- 26885184 TI - Anti-arrhythmic effects of atrial ganglionated plexi stimulation is accompanied by preservation of connexin43 protein in ischemia-reperfusion canine model. AB - BACKGROUND: Vagal nerve stimulation (VNS) has been shown to provide a protective effect against ischemia/reperfusion (I/R)-related arrhythmias by preventing the loss of Connexin43 (Cx43). Our previous studies showed that atrial epicardial ganglionated plexus stimulation (GPS) might exert a VNS-like effect on ventricular electrophysiology. OBJECTIVES: To investigate whether GPS could preserve Cx43 and reduce I/R induced ventricular arrhythmia. METHODS: Sixteen dogs were randomly divided into GPS group (N = 8, receiving GPS) and Sham group (N = 8, receiving sham GPS). Ventricular effective refractory period (ERP) and heart rate variability (HRV) were measured at baseline and 1 h after GPS. Myocardial I/R was then performed. Ventricular arrhythmia occurred during the first hour after reperfusion was measured and myocardial tissue from the peri infarct zone was excised for immunohistological analysis. In another 4 dogs (Control group, receiving sham GPS and sham I/R), myocardial tissue from the corresponding area was also excised. RESULTS: Compared with the Sham group, GPS caused a significant increase in ventricular ERP and HRV, and a significant decrease in I/R-induced ventricular arrhythmias. Western blotting revealed a marked reduction in the amount of phosphorylated Cx43 and total Cx43 in the Sham group, whereas no significant change was observed in the GPS group compared with the Control group. Immunohistochemistry results confirmed that the myocardial I/R induced loss of phosphorylated Cx43 from the intercellular junctions was prevented by GPS. CONCLUSION: GPS protects against I/R induced ventricular arrhythmias, accompanied by preserving Cx43. PMID- 26885183 TI - The Chronic Kidney Disease Epidemiology Collaboration equation improves the detection of hyperfiltration in Chinese diabetic patients. AB - OBJECTIVE: Hyperfiltration confers an increased risk of diabetic nephropathy. Early detection can ensure timely intervention and improved treatment outcomes. Because GFR is known to be affected by hyperglycemia, the aim of this study was to compare the influence of hyperglycemia on GFR estimations calculated by the CKD-EPI equation, the CG equation, and the MDRD equations in estimating hyperfiltration in Chinese diabetic patients. MATERIALS AND METHODS: The performance of the equations, compared with the measured (99)mTc-DTPA glomerular filtration rate was analyzed in 3492 diabetic patients. Bias, precision, and accuracies were compared with respect to HbA1c status. The Bland-Altman method was used to evaluate the agreement among the equations with respect to the mGFR, and the receiver-operating characteristic curve method was used to evaluate diagnostic value of the three equations with respect to the detection of moderate renal failure and hyperfiltration. RESULTS: The mean absolute bias was the smallest for the CKD-EPI equation in the HbA1c < 7.2% cohort, and the highest accuracy within +/- 15% and +/- 30% was also reached with the CKD-EPI equation in both cohorts. For the detection of hyperfiltration, the CKD-EPI equation exhibited the best performance with the greatest combination of sensitivity and specificity. The biases of the three equations were significantly higher in the HbA1c >= 10.5% subgroup compared with the HbA1c < 7.2% cohort. CONCLUSION: The CKD-EPI equation can be used as a screening tool for hyperfiltration and appears to be a more generalizable and accurate equation for estimating GFR in Chinese diabetic patients. PMID- 26885185 TI - Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects. AB - This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age < 40, sample size > 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease. PMID- 26885186 TI - Arginine vasopressin antagonist tolvaptan in the treatment of heart failure: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Tolvaptan can promote water clearance without a deterioration of serum electrolytes in HF patients, but its efficacy and safety were unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the efficacy and safety of tolvaptan in the treatment of patients hospitalized for heart failure (HF). METHODS: In Oct 2014, a literature search was started and found all studies conducted from 2000 to 2014. We systematically searched the literature through the MEDLINE database and EMBASE database. Quality assessments were evaluated with Jadad quality scale. Data were extracted considering the characteristics of efficacy and safety designs. RESULT: Eight RCTs enrolling 13453 participants satisfying the inclusion criteria were finally analyzed. There were significant decreases of body weight (MD=-0.87, 95% CI=-0.94 to -0.80, P<0.001) among all subgroups. Significant increase of serum sodium was found between tolvaptan and placebo groups at day 1 (MD=2.93, 95% CI=2.70 to 3.16, P<0.001) and at day 7 or discharge (MD=3.10, 95% CI=2.78 to 3.42, P<0.001). There were significant differences between the day 1 subgroup and day 7 or discharge subgroup (MD=2.99, 95% CI=2.80 to 3.18, P<0.001). A statistical significant improve in dyspnea (RR=1.10, 95% CI=1.07 to 1.13, P<0.001) and edema (RR=1.05, 95% CI=1.02 to 1.08, P<0.001) occurred, whereas there was no difference in rales (RR=2.38, 95% CI=0.89 to 6.38, P=0.08) and pulmonary congestion (RR=1.02, 95% CI=0.71 to 1.45, P=0.93). Pooled effect measure in the outcome of common adverse event (RR=1.08, 95% CI=0.99 to 1.18, P=0.08) and serious adverse (RR=0.96, 95% CI=0.88 to 1.04, P=0.29) event both show no significant occurrence. CONCLUSION: Tolvaptan decreases body weight, increases serum sodium, and improves congestion without significant increasing adverse events in HF patients. PMID- 26885187 TI - Baicaleininhibits VSMCs proliferation via regulating LncRNAAK021954 gene expression. AB - Atherosclerosis is responsible for the global medical burden of cardiovascular diseases, of which the proliferation of vascular smooth muscle cells (VSMCs) plays a key role in the development. Recent evidences demonstrated that baicalein could attenuate the proliferation of VSMCs and had no influence on VSMCs migration. However, the precise molecular mechanisms of baicalein inhibiting the proliferation of VSMCs were not clear. In this study, we investigated the viability and apoptosis behaviour of VSMCs and its downstream molecular changes with exposed to different dose of baicalein. Firstly, we observed significant reducing in the VSMCs proliferation and decreasing of FGF18 expression in a dose dependent manner after addition of baicalein for 24 h and 72 h. Moreover, the mRNA expression profile of VSMCs after treatments was evaluated by microarray analysis. Microarray analysis showed that long non-coding RNA (lncRNA) AK021954 gene expression was significantly increased in the baicalein treated group compared with the control group. Inversely, the VSMCs proliferation showed a notable increase after small silent RNA of lncRNAAK021954 treatment. These results indicated that lncRNAAK021954 gene and FGF18 involved in baicalein inhibiting the proliferation of VSMCs. It may provide a promising method in treatment of atherosclerosis. PMID- 26885189 TI - Roles of miR-186 and PTTG1 in colorectal neuroendocrine tumors. AB - OBJECTIVES: This work aims to investigate the expression of miRNA-186 in patients with colorectal cancer tissues, blood and feces and its roles in regulating the infiltration and invasion in colorectal cancer. METHODS: Totally 39 patients with surgical resection were included from August 2012 to February 2015 in Jilin Province People's Hospital as the Colorectal Neuroendocrine tumor (CNET). Peripheral blood, stool, and resected tumor tissues with adjacent normal of each patient was collected. In the same period, the blood and stool from 25 patients with hemorrhoids or other non-neoplastic diseases were collected and these samples used as clinical control group. MiR-186 expression and PTTG1 (pituitary tumor-transforming 1) expression were detected by quantitative Real-Time PCR (qRT PCR). The PTTG1 protein expression in tumor samples were detected by Western Blot, while its expression in blood and stool were detected by Elisa. RESULTS: Compared with the control group, the expression of PTTG1 mRNA and protein was significantly up-regulated in tumor samples, blood, and stool of patients with CNET, while the expression of miR-186 was down-regulated (P < 0.05). CONCLUSION: PTTG1 expression was significantly up-regulated in patients with CNET, which was induced by the down-regulated miR-186. MiR-186 may participate in the regulation of infiltration and invasion in CNET patients through targeting PTTG1 expression. PMID- 26885188 TI - Targeting SLUG sensitizes leukemia cells to ADR-induced apoptosis. AB - BACKGROUND AND AIMS: Slug is an E-cadherin repressor and a suppressor of PUMA (p53 upregulated modulator of apoptosis) and it has recently been demonstrated that Slug plays an important role in controlling apoptosis. In this study, we examined whether Slug's ability to silence expression suppresses the growth of leukemia HL-60 cells and/or sensitizes leukemia HL-60 cells to adriamycin (ADR) through induction of apoptosis. METHODS: SLUG siRNA was transfected into the HL 60 and HL-60(ADR) cell lines (an adriamycin resistant cell line). The stably SLUG siRNA transfected HL-60 and HL-60(ADR) cells was transiently transfected with PUMA siRNA. The mRNA and protein expression of SLUG and PUMA were determined by Quantitative real-time RT-PCR and Western blot assay. The effects of SLUG siRNA alone or combined with ADR or PUMA siRNA on growth and apoptosis in HL-60 and HL 60(ADR) cells was detected by MTT, ELISA and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. RESULTS: The results showed that SLUG was less expressed in the HL-60 cells, and high expressed in the HL 60(ADR) cells. Obvious down-regulation of SLUG mRNA and protein levels and up regulation of PUMA mRNA and protein levels after SLUG siRNA transfection was showed in the HL-60(ADR) cells. Treatment with ADR induced SLUG mRNA and protein in the HL-60 cells. Significant positive correlation was observed between basal SLUG mRNA and protein and ADR sensitivity. SLUG gene silencing by SLUG siRNA transfection inhibited growth and induced apoptosis, and increased ADR killing of the HL-60 and HL-60(ADR) cell lines. After the SLUG siRNA transfected HL-60 and HL-60(ADR) cells was transiently transfected with PUMA siRNA, did not increase ADR killing of the HL-60 and HL-60(ADR) cell lines. CONCLUSION: SLUG level positively correlated with sensitivity to ADR. SLUG siRNA could effectively reduce SLUG expression and induce PUMA expression and restore the drug sensitivity of resistant leukemic cells to conventional chemotherapeutic agents. PMID- 26885190 TI - Effects of Ukrain on intestinal apoptosis caused by ischemia-reperfusion injury in rats. AB - BACKGROUND: To investigate the antiapoptotic effect of Ukrain on intestinal lesion induced by mesenteric ischemia-reperfusion (I/R) injury. METHODS: Male Sprague-Dawley rats were divided into three groups: laparotomy (L), I/R, and Ukrain and I/R (U + I/R). In the U + I/R group, Ukrain (7 mg/kg) was given by intraperitoneal at the beginning of the study. 1 h after ukrain application, ischemia was induced for 30 minutes, and reperfusion was subsequently allowed for 120 minutes in the I/R and U + I/R groups. Rats were sacrificed at the end of reperfusion and intestinal tissues were collected for biochemical and molecular examination. Intestinal tissues caspase 3 protein were assayed. Serum Bcl-xL and iNOS were measured. The expression level of caspase-3, Bcl-xL and iNOS in intestinal tissue of rats were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Levels of serum iNOS and mRNA expression were increased in the I/R and decreased in the U + I/R group. In addition, levels of the proapoptotic gene caspase-3 protein and mRNA expression were increased in the I/R and decreased in the U + I/R group. Levels of the antiapoptotic gene Bcl-xL serum and mRNA expression were increased in the U + I/R group. CONCLUSIONS: Ukrain can reduce the ischemia-reperfusion injury in the intestinal tissue by inhibiting the cell apoptosis. The mechanism may be correlated with increased Bcl xL mRNA expressions and decreased mRNA expressions of Caspase-3 and iNOS. PMID- 26885191 TI - Association of risk of non-Hodgkin's lymphoma with hepatitis B virus infection: a meta-analysis. AB - OBJECTIVE: A meta-analysis was carried out to systematically evaluate the correlation between hepatitis B virus (hepatitis B virus, HBV) infection and risk of non-Hodgkin's lymphoma (non-Hodgkin lymphoma, NHL). METHODS: We searched Medline, EMBASE, PubMed, Cochrane Library, Chinese Biomedical Literature Database, Chinese Journal Full-text Database, Chinese scientific journals full text databases and collected information about HBV infection and risk of NHL associated case-control studies. Two reviewers extracted useful information which were included in the study independently, and Revman 5.2 was used for meta analysis. RESULTS: A total of 24 studies were included in this research. Meta analysis showed that among all of the included studies the heterogeneity were existed (I(2) = 76%, P<0.05). With random effects model the OR was 2.39 (95% CI, 1.93-3.96), indicating infection rate in NHL patients with HBV was higher than that in the control group. Subgroup analysis according to ethnicity suggested that HBV infection were associated with NHL risk both in Asian (OR = 2.46, 95% CI: 2.01, 3.00, P<0.001) and Caucasian (OR = 2.15, 95% CI: 1.37, 3.37, P<0.001) population. CONCLUSION: HBV infection may increase the risk of NHL, but it still need a large number of experiments and epidemiological studies to verify. PMID- 26885192 TI - Therapeutic effects of OP-1 on metal wear particle induced osteoblasts injury in vitro. AB - Aseptic lossening is a main reason for the revision of total joint arthroplasty. Metal-wear particles induced deregulation of bone resorption or formation has been considered as the major process of aseptic lossening. Osteogenic protein-1 (OP-1) can be used to improve bone formation. However, such effect is not clearly understood after the metal-wear particles injury. Here, we investigated the molecular mechanisms by which OP-1 regulates the activity of bone formation and anti-inflammatory after injury. Results showed that OP-1 increased cell viability and bone formation ability of impaired osteoblast cells at 72 hours after being injured by cobalt particles. Pathway analyses revealed that both mRNA and protein levels of Smad1 and Smad5 were significantly increased upon the treatment of OP-1 in the cell injury model. Similarly, runt-related transcription factor 2 (Runx2) was also significantly upregulated in the OP-1 treated cells. Moreover, treatment with OP-1 inhibited the secretion of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-18 in cobalt impaired cells. Collectively, these results suggest that OP-1 could inhibit cobalt particles induced cell injury by activating Smad1, Smad5, and Runx2, and such procedure is accompanied by anti inflammatory reaction. PMID- 26885193 TI - RKIP suppresses the proliferation and invasion ofchoriocarcinoma cells through inhibiting the MAPK signaling pathway. AB - Raf kinase inhibitor protein (RKIP), an inhibitor of Raf-mediated activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), has been identified as a metastasis suppressor gene. However, the role of RKIP in human choriocarcinoma remains undetermined. Therefore, in the present study, we investigated the expression of RKIP in human choriocarcinoma cells and evaluated the effects of RKIP on choriocarcinoma cell proliferation and invasion. Our results indicated that RKIP was lowly expressed in human choriocarcinoma cells. Overexpression of RKIP inhibits choriocarcinoma cell proliferation, migration and invasion, promotes the apoptosis of choriocarcinoma cells. Furthermore, overexpression of RKIP significantly inhibited the expression of MEK and ERK phosphorylation in choriocarcinoma cells. Taken together, these data suggest that RKIP suppresses cell proliferation and invasion in choriocarcinoma cells through inhibiting the MAPK signaling pathway, implying that RKIP may serve as a potential molecular target for the treatment of human choriocarcinoma. PMID- 26885194 TI - Eupatilin protects against tumor necrosis factor-alpha-mediated inflammation inhuman umbilical vein endothelial cells. AB - Inflammatory responses in the blood vessel play a pivotal role in the pathogenesis of atherosclerosis. Eupatilin, a flavone derived from Artemisia princepsPampanini, has various pharmacological activities, including antioxidant, anti-tumor, and anti-inflammatory capacities. However, there has been no research examining the function of eupatilin on vascular inflammation. Therefore, the aim of this study was to investigate the effects of eupatilin on tumor necrosis factor (TNF)-alpha-induced human umbilical vein endothelial cells (HUVECs) activation and the underlying molecular mechanisms. Our findings showed that eupatilin reduced U937 cells adhesion to TNF-alpha-stimulated HUVECs and attenuated TNF-alpha-induced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs, as well as the production of intracellular reactive oxygen species (ROS). Moreover, eupatilininhibits TNF-alpha-induced phosphorylation of NF-kB p65 and MAPKs in HUVECs. Taken together, the results of the present study suggest that eupatilin inhibited inflammatory reaction through suppressing the ROS/MAPK-NF-KB pathway in HUVECs. Thus, eupatilin is proposed as an effective new anti-inflammatory agent to suppress vascular inflammation, and further prevent atherosclerosis. PMID- 26885195 TI - Clinicopathological significance of NGX6 expression in breast cancer and its relationship to angiogenesis. AB - OBJECTIVE: The aim was to explore clinicopathological significance of Nasopharyngeal carcinoma-associated gene 6 (NGX6) expression in breast cancer and its relationship to angiogenesis. METHODS: Clinicopathological feature of 168 patients with breast cancer were analyzed. NGX6 expression and microvessel density (MVD) in tumor tissue were measured using immunohistochemistry methods. The association of NGX6 expression with MVD and clinicopathological features was assessed. RESULTS: Among 168 cases of breast cancer, NGX6 positive expression were found in 92 (54.8%) cases and NGX6 negative expression were found in 76 (45.2%) cases. Incidence rate of large size tumor, high tumor node metastasis (TNM) stage and lymph node metastasis in NGX6 negative expression group were higher than NGX6 positive expression group in breast cancer (P=0.003, 0.007, and 0.003, respectively). MVD in NGX6 negative expression group is 22.5+/-4.8, MVD in NGX6 positive expression group is 15.2+/-4.2. MVD in the NGX6 negative expression group was significantly higher than the NGX6 positive expression group (P<0.05). CONCLUSION: The expression of NGX6 was closely associated with tumor size, TNM stage, lymph node metastasis and MVD. NGX6 is involved in metastasis and angiogenesis activity of breast cancer. The study may provide a theoretical basis for anti-angiogenic therapy of breast cancer. PMID- 26885196 TI - Cytoplasmic EpCAM over-expression is associated with favorable clinical outcomes in pancreatic cancer patients with Hepatitis B virus negative infection. AB - The identification of reliable prognostic markers that distinguish patients' status and predict therapeutic response can improve the clinical outcomes of pancreatic cancer patients. The epithelial cell adhesion molecule (EpCAM) is known to be highly expressed in cancers and serves as a prognosis factor. Generally, membranous EpCAM expression in cancer cells and its clinical significance are evaluated. However, there is also an evidence of cytoplasmic EpCAM distribution in cancer cells. Hence, we investigated which kind of the immunostaining pattern in pancreatic cancer patients was, and whether membranous or cytoplasmic immunostaining had clinical significance. We determined the cytoplasmic or membranous EpCAM expression by a well-established immunohistochemical staining protocol in 157 pairs of carcinoma and paired adjacent non-tumor pancreatic tissue samples using the EpCAM-specific antibody. Furthermore, we evaluated the relationship between tumoral EpCAM expression of resected specimens and patient's overall survival as well as other biological variables like clinical prognosis by Kaplan-Meier method and chi(2) test. We found that pancreatic cancer patients had expressed higher level of cytoplasmic EpCAM but lower level of membranous EpCAM, and their expressions were significantly correlated. Cytoplasmic EpCAM acted as a favorable prognosis factor on survival time in patients with HBV negative infection. Pancreatic cancer patients with cytoplasmic EpCAM over-expression and negative Hepatitis B virus infection might benefit further from post-surgery chemotherapy. These data suggested a potential role of cytoplasmic EpCAM in predicting patient's prognosis and determining therapeutic strategy. PMID- 26885197 TI - Erythromycin enhances the anti-inflammatory activity of budesonide in COPD rat model. AB - Glucocorticoids (GCs) have been widely applied to treat patients with chronic obstructive pulmonary disease (COPD). But the effect of GCs was not ideal. This study was to observe whether erythromycin could enhance the anti-inflammatory activity of budesonide in COPD model rats and to explore the mechanism involved. In this study, male Sprague-Dawley rats were divided into five groups: healthy control group (H group), COPD model group (C group), erythromycin group (E group), budesonide group (B group) and erythromycin + budesonide group (E+B group). The rats in groups of C, E, B and E+B were developed into COPD models. Different groups were given different drug interventions. The levels of 8-iso PGF2alpha, IL-8, and TNF-alpha in BALF and serum were measured with ELISA. The protein expression levels of HDAC2, PI3K, and p-AKT in lung tissue were measured with Western-blot and immunohistochemistry. The levels of 8-iso-PGF2alpha, IL-8, and TNF-alpha in BALF and serum were lower in E+B group than those in B group and C group (all P<0.001).The protein expression level of HDAC2 was higher and PI3K and p-AKT were lower in E+B group than those in B group and C group (all P<0.001). Moreover, the expression levels of HDAC2 were negatively correlated with the levels of 8-iso-PGF2alpha, IL-8 and TNF-alpha both in serum and BALF and the expression levels of PI3K and p-AKT among the five groups, with all P<0.001. We conclude that erythromycin can enhance the anti-inflammatory activity of budesonide in COPD model rats, possibly through inhibiting the PI3K/AKT pathway and enhancing the activity of HDAC2. PMID- 26885198 TI - Evaluation of miR-29c, miR-124, miR-135a and miR-148a in predicting lymph node metastasis and tumor stage of gastric cancer. AB - MicroRNAs (miRNAs) are small noncoding RNA that have diverse functions in different biological process. The aim of this study was to evaluate the predictive ability of miR-29c, miR-124, miR-135a and miR-148a for lymph node metastasis (LNM) and tumor stage in gastric cancer. The expression of these miRNAs was detected and quantitated in gastric cancer tissues and in adjacent normal tissues from 60 patients by quantitative real-time reverse transcription polymerase chain reaction. CT imaging and clinicopathologic characteristics of these patients were performed. The result of this study was that these miRNAs were down-regulated in gastric cancer tissues; The low expression of miR-124 and miR-135a in LNM group and tumor III-IV stages (P < 0.01) presented the potential correlation with LNM and tumor stage; The two miRNAs were highly correlated with r = 0.730. Receiver operating characteristic curve analysis showed that miR-124 had better predictive ability to identify LNM and tumor stage. It could discriminate non-LNM from LNM with 80.0% sensitivity and 80.0% specificity and discriminate tumor Iota-II stages from tumor III-IV stages with 71.9% sensitivity and 75.0% specificity at the best cut-off value of 0.0125. Compared with CT imaging, miR-124 had similar specificity (0.800 versus 0.900, P = 0.508) but higher sensitivity (0.800 versus 0.500, P = 0.022) for lymph node assessment; Combined of miR-124 and CT imaging, The sensitivity and specificity of assessing LNM were raised to 83.3% and 90.0% respectively. Taken together, miR-124 may be a predictor for LNM and tumor stage in gastric cancer. PMID- 26885199 TI - Comparison of pullout strength of the thoracic pedicle screw between intrapedicular and extrapedicular technique: a meta-analysis and literature review. AB - BACKGROUND: Intrapedicular fixation in thoracic spine is often limited, because of high risk of complication, especially in scoliosis patients. Extrapedicular screws fixation techniques provide an alternate solution for extremely small or abnormal thoracic pedicles deformity. However, the pullout resistance of extrapedicular screws has not been clearly defined. The aim of our study was to systematically review the existing evidence regarding the pullout resistance of thoracic extrapedicular screws compared with intrapedicular screws. METHODS: A systematic search of all studies published through Nov 2014 was performed using Medline, EMBASE, OVID and other databases. All studies that compared the pullout resistance of thoracic extrapedicular screws with intrapedicular screws were selected. The data from the included studies were extracted and analyzed regarding pullout resistance force. Forest plots were constructed to summarize the data and compare the biomechanical stability achieved. RESULTS: Five studies were included, with a total of 27 cadaveric specimens and 313 screws. The vertebral levels of the cadavers potted were T1-T8, T2-T12, T7-T9, T6-T11 and T4 T12 respectively. Overall, the results demonstrated that there was no significant difference in ultimate pullout strength between intrapedicular screws and extrapedicular screws (95% CI=-63.73 to 27.74; P=0.44); extrapedicular screws significantly increased the length of placements by a mean of 6.24 mm (95% CI=5.38 to 7.10; P<0.001); while the stiffness in intrapedicular screws was significantly stronger by a mean of 45.82 N/mm compared with extrapedicular screws (95% CI=-70.09 to -21.56; P<0.001). CONCLUSIONS: Meta-analysis of the existing literature showed that thoracic extrapedicular screws provided comparable but slightly lower pullout strength compared with intrapedicular screws, extrapedicular screws placement is much safer than intrapedicular screws. So thoracic extrapedicular screws offer a good alternative when it is hard to insert by intrapedicular approach, especially in scoliosis patients with severe vertebral deformities. PMID- 26885200 TI - The BRAF V600E mutation predicts poor survival outcome in patients with papillary thyroid carcinoma: a meta analysis. AB - INTRODUCTION: There have been contradictory data on whether or not BRAF V600E mutation should be regard as a poor prognosis predictor of papillary thyroid carcinoma (PTC). To settle down the conflict, this metaanalysis is prepared to clarify the present prognostic role of BRAF V600E mutation in patients with PTC. METHODS AND MATERIALS: The relevant published researches were incorporated according to the defined inclusion/exclusion criteria from PubMed. The effect sizes of outcome parameters were estimated by hazard ratios (HRs). RESULTS: The current meta-analysis included 19 researches with a total of 6087 patients. We have found that patients with BRAF V600E mutation have a poor overall survival (the pooled HR=2.91, 95% confidence interval (CI): 1.35-6.29). Furthermore, subgroup analysis of the recurrence-free survival (RFS) of PTC patients by races indicated that BRAF V600E mutation predicts poor RFS of patients (the pooled HR=1.63, 95% CI: 1.37-1.93), both Caucasian (the pooled HR=1.57, 95% CI: 1.30 1.90) and Asian (the pooled HR=1.91, 95% CI: 1.28-2.87). CONCLUSIONS: The poor prognosis predicted role of BRAF V600E mutation in PTC was certified from the current meta-analysis. The BRAF V600E mutation may be used as a prognostic predictor of patients with PTC. PMID- 26885201 TI - Application of carbon nanoparticles for parathyroid protection in reoperation of thyroid diseases. AB - OBJECTIVE: To explore a new identification and protection method of the parathyroid gland in reoperation for thyroid diseases. METHOD: 54 patients receiving reoperation for thyroid diseases were selected. The experiment group intraoperatively adopted carbon nanoparticles suspension for negative development of the parathyroid gland, whereas the control group did not use carbon nanoparticles suspension. RESULTS: At 48 h after surgery, the parathyroid hormone level was lower than the normal state in 9 patients (33.30%) of the control group and 1 patient (3.70%) of the experiment group; meanwhile, 6 months after surgery, 8 patients of the control group (29.63%) and 1 patient of the experiment group (3.70%) showed a lower level than the normal state with statistical differences. The serum calcium level in 10 patients of the control group (37.04%) and 2 patients of the experiment group (7.41%) was lower than the normal state at 48 h after surgery, while a lower level than the normal state was also shown in 8 patients of the control group (29.63%) and 1 patient of the experiment group (3.70%) 6 months after surgery with statistically significant between the two groups. A total of 10 (37.04%) and 1 parathyroid gland (3.70%) were detected with a statistical difference in both groups. CONCLUSION: By adopting carbon nanoparticles in reoperation for the thyroid diseases and negative development of the parathyroid gland for identification and protection of the parathyroid gland, the incidence of hypoparathyroidism is reduced effectively, thus improving the postoperative quality of life of the patients. PMID- 26885202 TI - The development and application of electronic information system for safety administration of newborns in the rooming-in care. AB - OBJECTIVE: To independently research and develop an electronic information system for safety administration of newborns in the rooming-in care, and to investigate the effects of its clinical application. METHODS: By VS 2010 SQL SERVER 2005 database and adopting Microsoft visual programming tool, an interactive mobile information system was established, with integrating data, information and knowledge with using information structures, information processes and information technology. From July 2011 to July 2012, totally 210 newborns from the rooming-in care of the Obstetrics Department of the Second Affiliated Hospital of Nantong University were chosen and randomly divided into two groups: the information system monitoring group (110 cases) and the regular monitoring group (100 cases). Incidence of abnormal events and degree of satisfaction were recorded and calculated. RESULTS: 1 The wireless electronic information system has four main functions including risk scaling display, identity recognition display, nursing round notes board and health education board; 2 statistically significant differences were found between the two groups both on the active or passive discovery rate of abnormal events occurred in the newborns (P<0.05) and the satisfaction degree of the mothers and their families (P<0.05); 3 the system was sensitive and reliable, and the wireless transmission of information was correct and safety. CONCLUSIONS: The system is with high practicability in the clinic and can ensure the safety for the newborns with improved satisfactions. PMID- 26885203 TI - Interleukin-17F 7488T/C polymorphism is associated with protection against asthma: a meta-analysis. AB - The association between interleukin-17F (IL-17F) 7488T/C polymorphism and asthma risk is conflicting. This study conducted a meta-analysis by pooling all available data to make a more precise estimation of the association. Electronic databases PubMed, EMBASE, and China National Knowledge Infrastructure were searched to identify all eligible studies assessing the association between IL 17F 7488T/C polymorphism and asthma risk. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated. A total of five case-control studies with 1445 cases and 1608 controls were included. Overall, the pooled ORs showed that the IL-17F 7488T/C polymorphism was inversely associated with risk of asthma (OR=0.29, 95% CI=[0.12, 0.70]) using recessive genetic model. Furthermore, this association was found to be exclusive to Asians (OR=0.31, 95% CI= [0.12, 0.84]). Sensitivity analysis by omission of single study in turn showed similar results. In conclusion, the present meta-analysis suggested that homozygote of IL-17F 7488T/C variant could protect against asthma in Asians. However, more studies conducted in different ethnic groups with large sample size are warranted to validate the precise association. PMID- 26885204 TI - Programmed death-1 (PD-1) rs2227981 C > T polymorphism is associated with cancer susceptibility: a meta-analysis. AB - Several studies have focused on the correlation between the programmed death-1 (PD-1) rs2227981 C > T polymorphism and the risk of cancer; however, the results of such studies remain conflicting. To address this gap, we performed this meta analysis to identify the potential association. Search strategies were performed in PubMed and EMBASE using appropriate terms. In total, 2,977 cancer cases and 2,642 controls from seven publications were recruited in our study. According to the seven eligible publications, the odds ratios (ORs) and 95% confidence intervals (CIs) on the risk of cancer for the TT vs. CC and TT vs. CT+CC genotypes were 0.67 and 0.50-0.91 and 0.65 and 0.47-0.90, respectively. In a subgroup analysis by cancer type, PD-1 rs2227981 C > T polymorphism was associated with a significantly decreased risk of breast cancer (OR, 0.82; 95% CI, 0.71-0.95; P = 0.009 for T vs. C and OR, 0.76; 95% CI, 0.63-0.92; P = 0.005 for TT+CT vs. CC) and of other cancer (OR, 0.58; 95% CI, 0.36-0.92; P = 0.004 for TT vs. CT+CC). In a subgroup analysis by ethnicity, a significant decreased cancer risk was identified among Asians (OR, 0.74; 95% CI, 0.63-0.86; P < 0.001 for T vs. C and OR, 0.71; 95% CI, 0.59-0.87; P = 0.001 for TT+CT vs. CC) and among Caucasians (OR, 0.66; 95% CI, 0.44-0.99; P = 0.047 for TT vs. CT+CC). These findings highlight the fact that the T allele of PD-1 rs2227981 C > T polymorphism modestly decreases the susceptibility of cancer. Nevertheless, further large and well-designed studies are needed to enrich the evidence of this association. PMID- 26885206 TI - The association between serum ferritin with colorectal cancer. AB - There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum level of ferritin than the healthy controls (SMD=-1.569, 95% CI=[-2.718, -0.420], P= 0.007). Further subgroup analysis found lower serum level of ferritin among patients with colorectal cancer in eastern country (SMD= 1.956, 95% CI=[-3.750, -0.162], P=0.033), but not in western country (SMD=-1.285, 95% CI=[-2.778, 0.207], P=0.091). In conclusion, this meta-analysis supports a significant association between serum ferritin with colorectal cancer. However, the subgroup analysis found that there was significant effect modification of ferritin level by ethnic. Thus this finding needs further confirmation by trans regional multicenter, long-term observation in a cohort design to obtain better understanding of causal relationships between serum ferrintin levels and colorectal cancer, through measuring ferritin at baseline to investigate whether the highest ferritin category versus lowest is associated with colorectal cancer risk. PMID- 26885205 TI - Clinical anatomy and mechanical tensile properties of the rectus femoris tendon. AB - PURPOSE: We aimed to provide anatomical data and mechanical tensile properties for the rectus femoris tendon to determine if it is a feasible substitute for the anterior cruciate ligament during knee joint reconstruction. METHODS: The length and width of the quadriceps femoris tendon were measured from ten adult cadavers (20 knees; age =48+/-2 years). The anatomic features of the patellar insertion on the quadriceps femoris tendon were also documented. The rectus femoris tendon and anterior cruciate ligament were harvested from an additional five fresh specimens (10 knees; age =41+/-3 years). To minimize dehydration, each specimen was wrapped in saline-moistened paper towels and stored at -10 degrees C. We imposed tensile stresses on a total of twenty samples in a sample-driven machine at 10 mm/min until the specimens failed. RESULTS: The inserted and discrete widths of the rectus femoris tendon were 3.20+/-0.33 and 1.28+/-0.25 cm, respectively. The length of the tendon tissue was 6.96+/-0.80 cm and the length of mixing zone was 3.81+/-0.53 cm. The average thickness of the upper pole of the patella was 2.22+/ 0.14 cm. In mechanical tensile properties, the unit modulus and unit maximum load of the rectus femoris tendon were both 63% of the anterior cruciate ligament. CONCLUSIONS: Based on its anatomical and mechanical tensile properties, the rectus femoris tendon is a feasible donor site to reconstitute the anterior cruciate ligament. PMID- 26885207 TI - Assessment and prognostic analysis of EGFR mutations or/and HER2 overexpression in Uygur's Non-small Cell Lung Cancer. AB - AIM: The epidermal growth factor receptor (EGFR) mutations and human epidermal growth factor receptor HER-2/neu (HER2) have been established roles in the signal transduction pathways leading to cell growth and differentiation. The present study focus on the significance of EGFR mutations combined with HER2 overexpression on survival outcomes in Non-small Cell Lung Cancer patients in Uygur population. METHODS: A total of 111 consecutive Uygurods: A total of 111 consecutive Cell Lung Cancer under went lung Cell Lung biopsy or surgery at the Affiliated Tumor Hospital of Xin Jiang Medical University between March 2009 and January 2013 were included in this retrospective study. All the patients included had received gefitinib 250 mg once daily. The HER2 expression were evaluated by immunohistochemical staining with score of membranous staining being 0 = none, 1 = weak, 2 = 10-30% cells, 3>=30% cells stained, and Real-time PCR techniques were conducted to detect mutations of EGFR through 21 kinds of human EGFR gene mutation detection kits. A retrospective review of the medical records was analyzed to determine the correlation between the presence of EGFR mutations combined with HER2 overexpression and clinicopathological factors. RESULTS: The overall rate of EGFR mutation was 10.81% (n = 12), which mainly involved exons 19 (83.33%, n = 10), 21 (16.67%, n = 2). The overall rate of HER2 overexpression was 21.62% (n = 24). EGFR mutation combined with HER2 overexpression analysis was performed in 111 patients, with an overall rate of 5.41% (n = 6). Median progression-free survival and overall survival were significantly longer in the EGFR mutations group than in the wild type group (PFS: 10.0+/-1.5 versus 3.8+/ 1.4 months, P = 0.000; OS: 27.3+/-2.9 versus 19.1+/-4.7 months, P = 0.000). The ORR in patients with HER2 overexpression was 29.17%, and 13.80% in those patients with HER2 negative, but no significant difference (P = 0.121). The median PFS and OS in HER2 positive group showed no significant difference compared with HER2 negative group (PFS: 4.7+/-1.2 months versus 3.9+/-1.6 months, P = 0.085; OS: 20.5+/-2.4 versus 19.2+/-2.6 months, P = 0.094). As regarding to ORR, PFS and OS, EGFR mutations combined with HER2 overexpression patients showed no superior efficacy to gefitinib treatment compared with EGFR mutations combined with HER2 negative. CONCLUSION: In Uygur population, progression-free survivals were improved in Non-small Cell Lung Cancer with EGFR mutations. HER2 overexpression provided a poor prognostic factor in Non-small Cell Lung Cancer. PMID- 26885208 TI - Evaluation of the impact of Flos Daturae on rat hepatic cytochrome P450 enzymes by cocktail probe drugs. AB - Flos Daturae, known as "baimantuoluo" or "yangjinhua" in China, has been used for centuries in Traditional Chinese Medicine for the treatment of asthma, convulsions, pain, and rheumatism. To investigate the influences of Flos Daturae on the activities of rat CYP450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (10 mg/kg), tolbutamide (1 mg/kg), omeprazole (10 mg/kg), bupropion (10 mg/kg), metoprolol (10 mg/kg) and testosterone (10 mg/kg), was intragastric administered to rats treated with a single low or high dose of Flos Daturae decotion for 7days. Blood samples collected at a series of time-points in plasma were determined by UPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 3.0. The results from the present in vivo study showed that Flos Daturae induce the activity of CYP2D6 enzyme with the decreased Cmax, AUC(0-infinity) (P < 0.05) and the increased CL (P < 0.05). However, there were no significant differences of other probe drugs in plasma concentration and pharmacokinetic parameters. There were no significant effects on rat CYP1A2, CYP3A4, CYP2B6, CYP2C9 and CYP2C19 by Flos Daturae. Therefore, the resulting data suggested that caution was needed when Flos Daturae was co-administered with CYP2D6 substrates, which may result in treatment failure and herb-drug interactions. PMID- 26885210 TI - Extraction and antioxidant activity of flavonoids of Morus nigra. AB - Morus nigra has a long history of medicinal use in Chinese medicine, but the study on it is limited, the flavonoids are one of the main biological active substances. In this study, the Morus nigra flavonoids were extracted by ultrasonic and antioxidant activities both in vitro and in vivo were measured. The results showed that hydroxyl radicals clearance rate and superoxide radical anion clearance rate in vitro increased with the concentration of the total flavonoids in the range of 0-1.05 mg/mL and the maximum clearance rate was 80.33% and 87.69%, respectively. After mice were treated with flavonoids, the content of malonaldehyde (MDA) in serum and liver decreased; the activities of superoxide dismutase (SOD) in serum and liver, catalase (CAT) in liver and glutathione peroxidase (GSH-PX) in blood and liver increased; Langhans cells increased in spleen. These results revealed that the Morus nigra flavonoids possessed strong antioxidant activity. PMID- 26885209 TI - Do tumor volume, percent tumor volume predict biochemical recurrence after radical prostatectomy? A meta-analysis. AB - The aim of this meta-analysis was to explore the effects of tumor volume (TV) and percent tumor volume (PTV) on biochemical recurrence (BCR) after radical prostatectomy (RP). An electronic search of Medline, Embase and CENTRAL was performed for relevant studies. Studies evaluated the effects of TV and/or PTV on BCR after RP and provided detailed results of multivariate analyses were included. Combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models. A total of 15 studies with 16 datasets were included in the meta-analysis. Our study showed that both TV (HR 1.04, 95% CI: 1.00-1.07; P=0.03) and PTV (HR 1.01, 95% CI: 1.00-1.02; P=0.02) were predictors of BCR after RP. The subgroup analyses revealed that TV predicted BCR in studies from Asia, PTV was significantly correlative with BCR in studies in which PTV was measured by computer planimetry, and both TV and PTV predicted BCR in studies with small sample sizes (<1000). In conclusion, our meta-analysis demonstrated that both TV and PTV were significantly associated with BCR after RP. Therefore, TV and PTV should be considered when assessing the risk of BCR in RP specimens. PMID- 26885211 TI - CRMPs colocalize and interact with cytoskeleton in hippocampal neurons. AB - CRMP family proteins (CRMPs) are widely expressed in the developing neurons, mediating a variety of fundamental functions such as growth cone guidance, neuronal polarity and axon elongation. However, whether all the CRMP proteins interact with cytoskeleton remains unknown. In this study, we found that in cultured hippocampal neurons, CRMPs mainly colocalized with tubulin and actin network in neurites. In growth cones, CRMPs colocalized with tubulinmainly in the central (C-) domain and transition zone (T-zone), less in the peripheral (P-) domain and colocalized with actin in all the C-domain, T-zone and P-domain. The correlation efficiency of CRMPs between actin was significantly higher than that between tubulin, especially in growth cones. We successfully constructed GST CRMPs plasmids, expressed and purified the GST-CRMP proteins. By GST-pulldown assay, all the CRMP family proteins were found to beinteracted with cytoskeleton proteins. Taken together, we revealed that CRMPs were colocalized with cytoskeleton in hippocampal neurons, especially in growth cones. CRMPs can interact with both tubulin and actin, thus mediating neuronal development. PMID- 26885212 TI - Radiological analysis of degenerative lumbar scoliosis in relation to pelvic incidence. AB - PURPOSE: The purpose of this study was to identify the influence of pelvic incidence (PI) on spinopelvic parameters in patients with degenerative lumbar scoliosis (DLS) and compare them with those of a normal population. METHODS: There were two groups in this study. One group was composed by 136 patients with DLS and another was composed by 120 participants free of spinal disease. In each group there were three subgroups according to PI, which were low (PI less than 45 degrees ), middle (PI between 45 degrees and 60 degrees ) and high PI group (PI more than 60 degrees ). Sagittal spinopelvic parameters were compared between the DLS patients and asymptomatic participants in each PI group. RESULTS: The number of DLS patients with low, middle, and high PI were 38 (27.9%), 50 (36.8%), and 48 (35.3%), respectively. In the control group, the number of low, middle, and high PI participants were 52 (43.3%), 41 (34.2%), and 27 (22.5%), respectively. There were significant difference in PT, SS, LL, SVA and TLJ between the three subgroups in the DLS patients. Patients with high PI showed large TLJ, LL, PT, SS and small SVA. In the Control group and DLS group, PI determined pelvic orientation (PT, SS) and sagittal spinal parameters (LL, TLJ). In terms of correlation between SS and LL, between SS and TLJ, both DLS and Control groups showed significant correlations. In terms of correlation between PT and SVA, between PT and TLJ, only the DLS group showed a significant correlation. Compared with the asymptomatic participants, DLS patients showed a high PT and low SS as well as kyphotic TLJ, lumbar hypolordosis and thoracic hypokyphosis in all PI groups. CONCLUSIONS: The changes in spinopelvic parameters and pelvic compensatory mechanisms differ according to PI in patients with DLS, restoration of LL based on individual PI could help in accomplishing a balanced spinopelvic alignment. PMID- 26885213 TI - Application of back-propagation artificial neural network and curve estimation in pharmacokinetics of losartan in rabbit. AB - In order to develop pharmacokinetic model, a well-known multilayer feed-forward algorithm back-propagation artificial neural networks (BP-ANN) was applied to the pharmacokinetics of losartan in rabbit. The plasma concentrations of losartan in twelve rabbits, which were divided into two groups and given losartan 2 mg/kg by intravenous (Iv) and intragastrical (Ig) administration, were determined by LC MS. The BP-ANN model included one input layer, hidden layers, and one output layer was constructed and compared with curve estimation based on the time concentration data of losartan. The results showed the BP-ANN model had high goodness of fit index and good coherence (R > 0.99) between forecasted concentration and measured concentration both in Iv and Ig administration. The residuals of each concentrations generated by BP-ANN model were all smaller than Curve estimation. The pharmacokinetic result showed there was no significant difference between measured and simulated pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), MRT(0-t), MRT(0-infinity), T1/2 V and Cmax (P > 0.05). In conclusion, the BP-ANN model has remarkably accurate predictions ability, which better than Curve estimation, and can be used as a utility tool in pharmacokinetic experiment. PMID- 26885214 TI - Application experience of intraoperative neuromonitoring in thyroidectomy. AB - OBJECTIVE: The aim of this study is to summarize the experience of intraoperative neuromonitoring system for monitoring and protection of recurrent laryngeal nerve during thyroid surgery. METHODS: There were 220 cases in this study, male 53, female 167, mean age 38.2 years old. 85 cases in the study had thyroid cancer, 19 cases had thyroid benign tumor, 90 cases had thyroid goiter, 3 cases had Hashimoto's diseases, and 23 cases had hyperthyroidism. The tumor diameters were over than 5 cm in 113 cases. In the procedure, two recording needle electrodes were put into cricothyroid muscle; one stimulator electrodes was explored in tracheo-asophageal groove, if recurrent laryngeal nerves were right there or near, doctors could see the electromyogram and hear the toot honk. With careful dissection, recurrent laryngeal nerve could be found out till explored into the larynx site. RESULTS: 207 cases (278 sizes) of 220 were finished, electromyogram was not drawn out in 13 cases; 9 cases were false-negative because of system and anesthesia questions; needle electrodes cannot be put in properly in 4 cases because of cricothyroid muscle cancer invasion. No permanent recurrent laryngeal nerve paralysis occurred, 2 cases with transient nerve paralysis recovered in one month. CONCLUSION: The intraoperative neuromonitoring system can avoid damage of the recurrent laryngeal nerves when exposing the recurrent laryngeal nerve in the whole operation, therefore, with less medical complications. PMID- 26885215 TI - RAD51 Gene 135G/C polymorphism and ovarian cancer risk: a meta-analysis. AB - Previous studies suggest that the RAD51 gene 135G/C polymorphism could be potentially associated with the risk of ovarian cancer. However, results from observational studies are conflicting rather than conclusive. We performed a meta analysis of the literature aiming to clarify the relationship between the polymorphism of RAD51 gene 135G/C polymorphism and the risk of ovarian cancer. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We identified five eligible articles, 2336 ovarian cancer cases and 3548 controls. Meta-analysis results showed no significant association between 135G/C polymorphism in the RAD51 gene and ovarian cancer risk (GG vs CC: OR=0.42, 95% CI 0.16-1.06; GC vs CC: OR=0.37, 95% CI 0.12-1.16; Dominant model: OR=0.38, 95% CI 0.13-1.06; Recessive model: OR=1.20, 95% CI 0.91-1.58). No publication bias was found in the present study. This meta-analysis suggests that the RAD51 gene 135G/C polymorphism was not associated with risk of ovarian cancer. Further large and well-designed studies are needed to confirm this conclusion. PMID- 26885216 TI - Comparison between myocardial infarction and diabetes mellitus damage caused angiogenesis or energy metabolism. AB - This study aims to compare and analyze lactate dehydrogenase (LDH), succinic dehydrogenase (SDH) and differences in capillary density level in the model of myocardial damage which caused by rats diabetes. The Wistar rats were divided into 4 groups, including control, diabetic, myocardial infarction and two diseases combined group. Ligate descending branch of left coronary artery on 1/3 position or inject streptozotocin into abdominal cavity to establish two kinds of disease models. After 6 w, obtain the myocardial tissues to do the vascular density analysis of tissue sections which are stained and cell tissue enzyme. Explore change of relevant index and differences among groups. Results indicated that degree of LDH and SDH decrease in two kinds of disease model. Compared with control group, level of myocardial vascular of myocardial injury group is higher, and diabetic group is higher than non diabetic group. Quantitative result of FFA in mitochondrial suspension of single disease group is higher than that of control group and two diseases combined group. Level of FFA and LDH of two diseases combined group is consistent with control group. In conclusion, after myocardial damage, which is caused by diabetes mellitus or myocardial infarction, degree of local vascularization increases, diabetes mellitus is more obvious. After myocardial damage, process of myocardial mitochondrial glycolysis and oxidative phosphorylation has some obstacles. But these two kinds of diseases all have cardiac muscle cell which can keep generated procedure of aerobic and anaerobic energy to instead the normal function of cardiac muscle. PMID- 26885217 TI - Remove orthopedic fracture implant with minimal invasive surgery is good for the patient's early rehabilitation. AB - To explore the fact that minimal invasive osteosynthesis surgery could promote patient rehabilitate quickly. Patients needed to remove fracture fixation plates and screws in clavicle/femur/tibia and fibular bones were totally divided into two groups (conventional surgery group and minimal invasive surgery group). The operation time, intra-operative blood loose, post-operation 48 hours analgesic need, VAS score of 24-hours and 72-hours post-operation, post operation incision healing conditions, incision infection, patients' satisfaction about incision scar, and resting days were measured. Patients in the minimal invasive surgery group were satisfied with their scar condition than the conventional surgery group. There were no much difference between conventional surgery group and minimal invasive surgery group in operation time (46.3+/-10.2 minutes Vs 48.0+/ 11.8 minutes) (P>0.05) and the blood lose in these two groups were 4 ml Vs 47.4+/ 20.1 ml (P>0.05), respectively. There were no screws broken in both groups and all the implants were removed out successfully. Remove four limb fracture fixation implant with minimal invasive surgery is good for patients' early rehabilitation. PMID- 26885218 TI - Clinicopathological significance of Sox2 expression in patients with breast cancer: a meta-analysis. AB - Sex-determining region Y-box protein 2 (Sox2), an embryonic transcription factor located at chromosome 3q26.33, has been frequently demonstrated to be an important prognostic marker for various tumors, including breast cancer. However, its clinicopathological role in breast cancer has not been fully elucidated. To derive a more precise evaluation, we here performed a meta-analysis focusing on the association between Sox2 expression and various clinicopathological characteristics of breast cancer. Relevant publications were identified and retrieved using PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases. Ten studies with a total of 1713 patients with breast cancer were included in our meta analysis. Reported odds ratios (OR) and the corresponding 95% confidence intervals (95% CI) were pooled to assess the strengths of the analyzed associations. Our results revealed significant positive associations between Sox2 expression and increased tumor size (pooled OR=2.61, 95% CI=1.91-3.58), histological grade (pooled OR=2.28, 95% CI=1.72-3.03), lymph node metastasis (pooled OR=4.17, 95% CI=1.20-14.45), and the highly aggressive triple-negative phenotype (pooled OR=2.64, 95% CI=1.11-6.29). However, no associations were observed for TNM stage and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 statuses. Overall, the results of this meta analysis indicate that Sox2 may be considered as a prognostic marker for breast cancer. More well-designed studies with larger sample sizes are warranted to clarify the prognostic significance of Sox2 in breast cancer. PMID- 26885219 TI - Association between Interleukin-8-251A/T polymorphism and gastric cancer susceptibility: a meta-analysis based on 5286 cases and 8000 controls. AB - OBJECTIVES: Published data on the association between Interleukin-8-251A/T polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between cyclin D1 G870A polymorphism and GC risk. METHODS: We searched PubMed, EMBASE, Web of science and the Cochrane Library up to July 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. RESULTS: Twenty-six studies published from 2004 to 2015, with a total of 5286 cases and 8000 controls, were included in this meta-analysis. The pooled results showed that there was significant association between Interleukin-8-251A/T polymorphism and GC risk in any genetic model. In the subgroup analysis by ethnicity, the effects remained in Asians. However, no genetic models reached statistical association in Europeans. The subgroup analysis stratified by Source of controls showed an increased breast cancer risk in hospital-based (HB) studies in any genetic model except recessive model. However, there was no association in any genetic model in population based (PB) studies. When stratifying by Genotyping method, we found statistical association in Non-RFLP (restriction fragment length polymorphism) in any genetic model except heterozygote comparison, the effect was remain in PCR-RFLP in dominant model and heterozygote comparison. CONCLUSIONS: This meta-analysis suggests that Interleukin-8-251A/T polymorphism is a risk factor for susceptibility to GC in overall population, especially in Asians, in hospital populations and in Non-RFLP. While, there was no association in Europeans and in general population. Further large scale multicenter epidemiological studies are warranted to confirm this finding. PMID- 26885220 TI - Differences of prevalence of dyslipidemia and risk factors related to LDL-c in the patients with abnormal fasting glucose between Uygur and Han in Xinjiang. AB - AIMS: To evaluate the incidence of dyslipidemia among Uygur and Han patients with impaired fasting glucose (IFG). To investigate the influence factors on LDL-c in this population. METHODS: This cross-sectional study included a total of 4709 participants, consisting of Uygurs patients (n=2053) and Han patients (n=2656) from Xinjiang province, who were screened for diabetes mellitus. A stratified multistage sampling design was used to collect the participants. The influence factors on LDL-c were analyzed by Logistic regression analysis. RESULTS: Among the IFG patients (n=1757), Uighur IFG group had a higher prevalence of dyslipidemia than that of Han IFG group, 99.8% vs. 63.7%, P<0.05. Similar trends were existed in the prevalence of hypercholesteremia, hypertriglyceridemia, high LDL-c and low HDL-c (all P<0.05). Among the Uighur groups, IFG group had higher dyslipidemia rate than that of euglycemia group (74%). However, there was no such difference in the Han groups. Logistic regression analysis revealed that risk factors associated with LDL-c were age, total cholesterol and 2 h postprandial blood glucose for the Uighur IFG patients. However, gender and total cholesterol were risk factors for Han IFG patients. CONCLUSIONS: Uighur IFG patients had higher incidence of dyslipidemia than that of Han IFG patients. For Uyghur IFG patients, closing follow-up of total cholesterol and 2 h postprandial blood glucose were necessary. As to the Han IFG patients, we should pay more attention to male and total cholesterol in order to lower LDL-c levels. So, appropriately preventive and therapeutic measures should be chosen based on the characteristics of abnormal lipid profiles in different nationality. PMID- 26885222 TI - Value of high-frequency ultrasound in diagnosing carpal tunnel syndrome. AB - This study aimed to evaluate the diagnostic value of high-frequency ultrasound examination for carpal tunnel syndrome (CTS). A total of 63 wrists from 45 patients diagnosed with CTS were selected as the study group, and 43 asymptomatic wrists of 40 cases were included as the normal control group. Parameters such as the transverse diameter, vertical diameter, cross-sectional area (CSA), and flattening rate (FR) of the carpal tunnel radioulnar joint, postular bone, and median nerve in the hamate bone hook plane were measured, and the differences between the two groups were compared. The median nerve CSA in the postular bone plate was significantly greater in the study group than in the normal control group (0.17+/-0.05 vs. 0.09+/-0.02, P<0.01), and the FR at the hook of the hamate was significantly higher in the study group (3.52+/-0.86 vs. 3.21+/-0.26, P<0.01). Our results suggest that ultrasonography can effectively provide dynamic real-time images of the wrist in addition to being painless, non-invasive, and associated with relatively low costs. Based on our findings, we believe that ultrasonography is an effective examination method for CTS. When the threshold of the median nerve CSA in the postular bone plate was set as 10 mm(2), the diagnostic sensitivity and specificity were 92% and 86%, respectively. Therefore, the median nerve CSA may represent a good clinical indicator of CTS. PMID- 26885221 TI - Experimental and clinical analysis of a posterolateral lumbar appendicular bone graft fusion. AB - OBJECTIVE: This study aimed to investigate the animal experimental and clinical results of the bone graft fusion of a posterolateral lumbar appendicular bone. METHODS: 1. Sixty rabbits were randomly divided into experimental and control groups. Posterolateral lumbar bone graft with the appendicular bone and iliac bones, respectively, was then performed on these two groups. A lumbar spine X-ray was performed on the postoperative 4(th), 8(th) and 16(th) weeks, and the gray value changes of the bone graft fusion area were measured to calculate fusion rates. Histology analysis was also performed to observe and count osteoblasts. 2. The appendicular bones of 106 patients who suffered from lumbar disorders were cut during lumbar surgery, and a posterolateral lumbar bone graft was performed. The postoperative follow-up used the Steffee criteria to evaluate clinical efficacy and the White criteria to evaluate fusion conditions. RESULTS: No significant difference was observed in the relative gray values of X-ray bone density, bone graft fusion rates, and osteoblast counts in the bone graft regions between the two groups (P > 0.05). The follow-up duration of the 106 patients were 4-8 years (6.12 years), the clinical efficacy rate was 85.85%, and the fusion rate was 83.02%. CONCLUSIONS: The animal experimental and clinical results of posterolateral lumbar bone graft fusion with autologous iliac and appendicular bones were similar. PMID- 26885223 TI - Two different surgery approaches for treatment of thoracolumbar fracture. AB - BACKGROUND: To evaluate the safety and effectiveness of pedicle screw fixation for treatment of thoracolumbar fracture via Wiltse paraspinal approach. METHODS: From June 2009 to June 2012, we enrolled into our study 53 cases of thoracolumbar fractures (single segment compressive or burst fractures) without neurologic injury, among whom 28 were treated by mini-open operation via Wiltse approach (group A) and 25 by conventional posterior open surgery (group B). We recorded and compared the intraoperative and postoperative performance between the two groups. RESULTS: There was no serious complications occurring during our study, such as infection, blood vessel injury, spinal cord or nerve root injury. We did not find any statistically difference between the two groups in corrected rate of Cobb's angle or vertebral body height (P>0.05). However, the mini-open method had apparent advantages over the conventional open method in operative time, intraoperative blood loss, postoperative drainage, and postoperative improvement on visual analog scale (VAS) scores at 3 days, 1 month, and 6 months after operation (P<0.05). After 9-24-month follow-up, the number of patients with low back pain in group A was less than that in group B. CONCLUSION: In the premise of strict controlling surgery indications, pedicle screw fixation via Wiltse paraspinal approach has the advantages of simple operation and less trauma in treatment of single-segment thoracolumbar fracture without neurologic injury. PMID- 26885224 TI - Extramedullary relapse in lumbar spine of patient with acute promyelocytic leukemia after remission for 16 years: a case report and literature review. AB - Acute promyelocytic leukemia (APL) is a common myeloid leukemia. At the newly diagnosed stage, it can be fatal because of the serious complication-disseminated intravascular coagulation. With the advent and early application of all-trans retinoic acid, most APL patients can achieve a long-term survival, and only a minority of patients will develop extramedullary relapse after remission. The most common site of extramedullary relapse is central nervous system, while other sites are relatively rare. Here, we report a particularly rare APL patient who experienced extramedullary relapse with lumbar spine as the isolated site after a rather long time of remission for 16 years. At the time of relapse, the main clinical manifestations of the patient are obvious low back pain, weakness in lower limbs and limitation of activity. After treatment of local radiotherapy combined with ATRA and arsenic trioxide, the patient achieved and maintained a second complete remission by now. PMID- 26885225 TI - Human pituitary homeobox-3 gene in congenital cataract in a Chinese family. AB - OBJECTIVES: Congenital cataract is the common cause of world blindness. It is generally inherited as an autosomal recessive trait and has various phenotypes. This study aimed to explore the gene responsible for autosomal recessive congenital cataract in a Chinese family, and to investigate the functional and cellular consequences of the mutation. METHODS: A four-generation Chinese family with autosomal recessive congenital cataract was included in the study. A genome wide scan and linkage analysis were performed in the chromosomal region of Pituitary homeobox 3 (PITX3) to identify the linked region of the genome. And sequence analysis of PITX3 gene was also investigated using BigDye Terminator mix 3.0 and SeqScape Software 2.5. RESULTS: The genome wide scan and linkage analysis identified a disease-haplotype interva. The maximum logarithm of odds LOD score was (Zmax) 3.11 at marker D10S1693 (thetamax=0.00), flanked by D10S1680 and D10S467, which included the PITX3 gene. Sequencing revealed a splice site mutation, G->A, at D10S1680 and D10S467, which co-segregated with all the affected members of this family. CONCLUSIONS: The 543delG is a novel mutation in PITX3 causing an autosomal recessive congenital cataract. PMID- 26885226 TI - A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention. AB - The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID- 26885227 TI - Influencing factors on use of standard precautions against occupational exposures to blood and body fluids among nurses in China. AB - AIMS: To investigate how specific factors, including knowledge, attitude, use of protective devices, safety climate, workload, and nurses' behaviors can influence standard precautions in China through structural equation modeling techniques. BACKGROUND: Although a number of empirical studies have been conducted, an investigation of how multiple variables influence behaviors of standard precautions among the nurses is still needed. METHODS: The study was conducted by selecting registered nurses from 25 public hospitals that operate approximately 500 beds located in different areas of Guizhou Province in China. An anonymous, self-administered questionnaire was distributed to 1000 nurses, and 964 (96.4%) completed questionnaires were returned. exploratory factor analysis was employed to examine associations of attitudes, protective devices, safety climate, workload, and nurses' behaviors with standard precautions. The identified factors were integrated in the proposed structural equation model. FINDINGS: Protective devices had a positive and major influence on nurses' use of standard precautions. Knowledge had a positive impact on the use of standard precautions through attitude mediation, and the safety climate had a positive impact on the use of standard precautions. In contrast, increasing workload had a negative effect on the use of standard precautions. The factors affecting the use of standard precautions among nurses in order of decreasing effect size were: protective devices, knowledge, attitude, safety climate, and workload. CONCLUSIONS: This study offer valuable information for healthcare management regarding the use of standard precautions to reduce occupational exposure among nurses. PMID- 26885228 TI - Combined usage with intraperitoneal and incisional ropivacaine reduces pain severity after laparoscopic cholecystectomy. AB - Postoperative pain is the main obstacle for safely rapid recovery of patients undergoing laparoscopic cholecystectomy (LC). In this study, we systemically evaluated the analgesic efficacy of intraperitoneal and incisional ropivacaine injected at the end of the LC. A total of 160 patients, scheduled for elective LC, were allocated into four groups. Group Sham received intraperitoneal and incisional normal saline (NS). Group IC received incisional ropivacaine and intraperitoneal NS. Group IP received incisional NS and intraperitoneal ropivacaine. Group ICP received intraperitoneal and incisional ropivacaine. At the end of the surgery, ropivacaine was injected into the surgical bed through the right subcostal port and infiltrated at the four ports. Dynamic pain by a visual analogue scale (VAS) and cumulative morphine consumption at 2 h, 6 h, 24 h, and 48 h postoperatively, as well as incidence of side-effects over 48 h after LC was recorded. Compared with those in group Sham, the time of post-anesthesia care unit (PACU) stay, dynamic VAS score (VAS-D) 2 h and 6 h postoperatively, cumulative morphine consumption 6 h and 24 h postoperatively, and incidence of nausea and vomiting 48 h after LC in group IC and ICP were less (P<0.05). Furthermore, intraperitoneal and incisional ropivacaine exerts more powerful analgesic effect than single usage with intraperitoneal or incisional ropivacaine (P<0.05). No patients exhibited signs of local anesthetic toxicity. In conclusion, intraperitoneal and incisional ropivacaine might facilitate PACU transfer and effectively and safely reduce pain intensity after LC. PMID- 26885229 TI - Inhibition of adriamycin-induced nephropathy in rats by herbs based kangshenoral solution. AB - The Chronic kidney disease (CKD) is characterized by the progressive loss in renal function over a period. The progression of CKD will finally result the End Stage Renal Disease (ESRD) Symptoms which needs permanent renal replacement therapies. Therefore, control the progression of CKD is necessary. In this study, based on the theory of Traditional Chinese Medicine and the Traditional Chinese Herbology, we developed the Kangshen Oral Solution based ona combination of different herbs for extraction. By utilizing adriamycin (ARD)-induced chronic renal failure in rats as the CKD model, our results demonstrated thatadministration of the Kangshen Oral Solution reduced the kidney disease induced weight loss in rats. The Kangshen Oral Solution could also relieve the proteinuria and kidney index induced by ARD which indicated the partially restoration of the kidney function. The improved kidney function was further supported by biochemical tests for blood total protein level, albumin level as well as cholesterol, triglycerides and Creatinine. Moreover, the histology examination also confirmed the ARD induced pathological changes in kidney was relieved by Kangshen Oral Solution. Taken together, these findings suggested Kangshen Oral solution could reduce ARD-induced nephropathy in rats model and may be employed as an alternative treatment for CKD patients. PMID- 26885230 TI - Preclinical analysis of nonsteroidal anti-inflammatory drug usefulness for the simultaneous prevention of steatohepatitis, atherosclerosis and hyperlipidemia. AB - Nonalcoholic steatohepatitis (NASH) is currently one of the primary liver diseases. Recent studies have shown a clinical relation between NASH and atherosclerosis. There is much interest in these two diseases because they are both associated with great morbidity and mortality. Inflammation and the overexpression of COX-2 participate in the pathophysiology of the two diseases, and therefore simultaneous treatment is feasible. The role of the four NSAIDs, meclofenamate, mefenamate, flufenamate, and aspirin, was analyzed in a mouse model of NASH, as well as preclinical atherosclerosis induced by a high-fat diet (HFD). Six mouse groups were formed. Five of the groups were fed a high-fat diet for 6 months and one group was fed a standard diet, acting as the normality reference. Of the five groups fed a high-fat diet, four received a NSAID, each of them identified by the specific drug administered. One group received no treatment. Serum markers (cholesterol, triglycerides, ALT, and AST) and histologic changes in the aorta and liver were analyzed for the study. Aspirin significantly reduced the hepaticsteatosis. All the drugs significantly reduced the hepatic inflammatory infiltrate. In relation to atherosclerosis, there were significant reductions in all the study variables with the use of aspirin and flufenamate. The four medications were able to stop steatosis from progressing into steatohepatitis by reducing inflammation. However, aspirin was the most beneficial, simultaneously reducing steatosis, atherosclerosis, and serum cholesterol levels. PMID- 26885231 TI - Association study between growth differentiation factor 5 polymorphism and non contact anterior cruciate ligament rupture in Chinese Han population. AB - BACKGROUND: Anterior cruciate ligament (ACL) rupture is the most common ligamentous injury for active adolescents and young adults each year. However, the precise etiologies of ACL injury are not fully understood. The present study was to investigate +104T/C polymorphism of growth differentiation factor 5 (GDF5) gene in patients with ACL rupture, and evaluate the effects of polymorphism on GDF5 mRNA levels in ligament of patients with ACL rupture in central China. METHODS: A total of 286 Chinese patients with ACL rupture and 500healthy controls were enrolled in this study. The +104T/C polymorphism in GDF5 gene were genotyped by DNA sequencing. GDF5 mRNA expressions levels in ligament were determined by quantitative PCR. RESULTS: The frequency of the TT genotype tended to be higher in ACL rupture group than in control group (62.6% vs. 48.0%, P< 0.001, OR = 1.81, 95% CI: 1.35-2.44). T allele of the GDF5 +104T/C polymorphism was more common in ACL rupture group than in control group (P< 0.001). Patients carrying TT genotype expressed lower levels of GDF5 mRNA than C carriers (P = 0.005) among ACL rupture. CONCLUSION: Our study indicated that GDF5 +104T/C polymorphism was associated with ACL rupture patients in central China. This is likely from decreased expressions of GDF5 mRNA. Further studies are necessary to explore the functional implication of the GDF5 +104T/C polymorphism in Chinese ACL rupture patients. PMID- 26885232 TI - Sexual dysfunction in dialysis patients: does vitamin D deficiency have a role? AB - INTRODUCTION: Sexual dysfunction and vitamin D deficiency are highly prevalent in dialysis patients. Low levels of vitamin D have been linked to many diseases. To the best of our knowledge, the relationship between vitamin D and sexual dysfunction in dialysis patients has not been previously reported in the literature. MATERIALS AND METHODS: Cholecalciferol, 50,000 IU/week, was orally administered to 37 dialysis patients with vitamin D insufficiency for 3 months followed by dosage of 10,000 IU every other week for 3 months. The Arizona Sexual Experiences Scale (ASEX), Hospital Anxiety and Depression Scale and Pittsburgh Sleep Quality Index questionnaires were filled out by all patients at baseline and at the sixth month of the study. RESULTS: Sexual dysfunction, poor sleep quality, anxiety and depression rates were 83.7%, 45.9%, 18.9% and 48.6%, respectively in all patients. ASEX total score was found to be positively correlated with age and was negatively correlated with serum 25(OH)D level and serum albumin level. After cholecalciferol treatment, 25(OH)D levels increased significantly, however no significant change was observed in any of the parameters. In multivariate linear regression analysis, age and 25(OH)D level were found to be independent predictors of ASEX total score. CONCLUSIONS: Vitamin D deficiency seems to contribute to sexual dysfunction in dialysis patients. However, it was observed in this study that; cholecalciferol replacement given to dialysis patients with vitamin D insufficiency did not result in any significant changes in sexual functions. PMID- 26885233 TI - Replacement of conventional doxorubicin by pegylated liposomal doxorubicin in standard RCHOP chemotherapy for elderly diffuse large B-Cell lymphoma: a retrospective study in China. AB - Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of non-Hodgkin's lymphoma (NHL) in adults, and approximately 50% of cases of DLBCL occur in patients above the age of 60. Although RCHOP regimen was established as the standard therapy for DLBCL patients, there are still a large number of DLBCL patients who can't bear the toxicity of doxorubicin, especially in elderly patients. Pegylated liposomal doxorubicin (PLD) offers a new strategy for elderly DLBCL patients. In our study, we reviewed 103 newly diagnosed patients with DLBCL aged between 60 years to 75 years old who were treated with RCHOP (62 cases) or DRCOP (41 cases) regimen. All the patients completed a mean follow-up period of 28 months (range, 2 to 48 months). There was no statistical difference of OS between the DRCOP (78.0%) and RCHOP (72.6%) groups (P = 0.787). And there were less grade 3-4 cardiotoxicity in patients treated with DRCOP (9.8%) than RCHOP regimen (27.4%, P = 0.029). Our findings in this study indicate that the DRCOP regimen offers similar oncologic efficacy when weighed against the standard RCHOP regimen in elderly DLBCL patients, and it might be a more secure treatment for elderly DLBCL patients who have additional risk factors for cardiac diseases. PMID- 26885234 TI - Association study of BUD13-ZNF259 gene rs964184 polymorphism and hemorrhagic stroke risk. AB - We aimed to evaluate the association of rs964184 of BUD13-ZNF259 gene with the risk of hemorrhagic stroke (HS). A total of 138 HS cases and 587 controls were recruited for the association of rs964184 of BUD13-ZNF259 gene with the risk of HS. Tm shift PCR was used for genotyping. We were unable to find the association of rs964184 of BUD13-ZNF259 gene with the risk of HS (P>0.05). Significant difference was found in the TG level among the three genotypes (CC: 1.51+/-1.02; CG: 1.68+/-1.10; GG: 1.90+/-1.11, P=0.036). The TG level showed strong correlation with rs964184 genotypes (P=0.010, correlation=0.101). Significantly higher TC, HDL-C, and LDL-C levels were observed in the case group. And no difference was found in the TG, ApoA-I, ApoB. Our case-control study supported the significant association between rs964184 genotype and the blood TG concentration, although we were unable to find association between BUD13-ZNF259 rs964184 and the risk of HS in Han Chinese. PMID- 26885235 TI - Expressions and clinical significance of factors related to giant cell tumor of bone. AB - BACKGROUND: Giant cell tumor of bone (GCTB) is a relatively rare tumor of bone, characterized by numerous multinucleated cells, severe osteolysis, and local recurrence. PURPOSE: To explore the role of S-phase kinase-interacting protein 2 (Skp2), cyclin-dependent kinase inhibitor p27, and the transcription factor E2F-1 expression in the development of GCTB, and the relationship of expression of these proteins with tumor recurrence. METHODS: Forty-four patients with GCTB were selected and demographic and clinical data were collected. The levels of Skp2, p27, and E2F-1 protein expression were immunohistochemically assessed in surgical specimens. RESULTS: Skp2, p27, and E2F-1 proteins were detected in the nuclei of mononuclear stromal cells. Positive Skp2 expression was observed in 66% (29/44) of GCTB patient samples, and positive p27 expression was found in 39% (17/44) of samples. Within almost all GCTB patients, there was an inverse correlation between Skp2- and p27-positive tumor cells. Positive expression of E2F-1 was present in 28 of 44 (64%) patients. In addition, expression of skp2 and p27, infiltration of soft tissues, and surgical operation were significantly associated with recurrence in patients with GCTB. CONCLUSION: The immunohistochemical assessment of Skp2, p27 and E2F-1 may be useful in the diagnosis of GCTB and prediction of its prognosis. PMID- 26885236 TI - Clinicopathological associations of acquired erythroblastopenia. AB - INTRODUCTION: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. BACKGROUND: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. MATERIAL AND METHOD: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. RESULTS: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). DISCUSSION: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. CONCLUSION: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated. PMID- 26885237 TI - Levels of interleukin-16 in peripheral blood of 52 patients with multiple myeloma and its clinical significance. AB - PURPOSE: To explore the role of serum interleukin-16 (IL-16) in the occurrence of multiple myeloma (MM) and after the success chemotherapy and its clinical significance. METHODS: 52 cases of MM patients, 30 cases of AML patients and 30 healthy volunteers from Jan. 2011 to Jan. 2015 were collected in this study. There was 39 MM patients received chemotherapy. Among those, 24 patients received VAD regimen chemotherapy and 15 patients received BD regimen chemotherapy. Serum IL-16, cystatin C (Cys-C), lactate dehydrogenase (LDH) and levels of beta2 microglobulin (beta2-MG) were detected before and after the therapy of MM patients. And those results were compared to that of patients with acute myelogenous leukemia (AML) and normal people respectively. RESULTS: The levels of serum IL-16, Cys-C, LDH and beta2-MG in MM group were remarkably higher than that of normal control. It was of statistical significance of this difference (P<0.05). Levels of serum IL-16, Cys-C and LDH of MM patients who received therapy were all lower than that of patients before therapy. The serum IL-16 and beta2-MG of 52 patients by preliminary diagnosis were analyzed through Pearson correlation analysis before they received therapy. The results showed that there was positive correlation between levels of IL-16 and beta2-MG (r=0.782, P<0.01). CONCLUSIONS: A high serum IL-16 level detected in newly diagnosed MM patients and its correlation with known factors of disease activity as well as the decrease of IL-16 after chemotherapy suggest that IL-16 may be implicated and a potential therapeutic target for MM. PMID- 26885238 TI - Correlation between the BRAF(v600E) gene mutation and factors influencing the prognosis of papillary thyroid microcarcinoma. AB - OBJECTIVE: To evaluate the relationship between BRAF mutation and factors influencing the prognosis of papillary thyroid microcarcinoma (PTMC). METHODS: Clinical data from patients with PTMC were subjected to retrospective analysis. A total of 86 patients were included, and the BRAF(V600E) mutation was identified in surgically dissected tissues. RESULTS: The incidence of BRAF mutation in patients with PTMC was 65.1% (56/86). Both univariate and multivariate analyses indicated a correlation between BRAF mutation and lymph node metastasis (P = 0.057). For patients with tumors <= 10 mm in diameter, BRAF mutation had no effect on lymph node metastasis (P > 0.05). No lymph node metastasis was found in patients with tumors <= 5 mm in diameter. CONCLUSION: BRAF gene mutation is an independent predictive risk factor for central lymph node metastasis in patients with PTMC. For patients with preoperative BRAF mutation positivity, it is important to perform central lymph node dissection (CLND) and lymphatic and adipose tissues should be routinely removed. However, in patients without BRAF mutation and tumors <= 5 mm in diameter, the necessity of prophylactic CLND should be reevaluated. PMID- 26885240 TI - Role of serum high density lipoprotein levels and functions in calcific aortic valve stenosis progression. AB - BACKGROUND: Clinical and epidemiological data well defines the role of atherosclerotic risk factors in pathogenesis of aortic stenosis. Especially dyslipidemia with elevated total and LDL cholesterol levels exerts certain histopathological changes on calcified valve tissue. Exact role of HDL in this process is not known. OBJECTIVE: To evaluate the lipid profiles of patients with mild aortic valve stenosis with special focus on HDL; HDL subspecies, serum apoA1 levels, HDL related PON1 and PAF-AH enzyme activities and to correlate this with disease progression rates. METHOD: 42 patients (26 female; 16 male), with calcific aortic valve stenosis were enrolled in the study. Serum fasting lipid parameters, HDL subspecies (HDL2, HDL3), serum apoA1 levels and HDL related PON1 and PAF-AH enzyme activities were determined. All participants underwent detailed follow-up transthoracic echocardiography examination. RESULTS: Among 42 study participants mean serum total cholesterol level was 195 +/- 27.3 mg/dl, LDL-c level was 123 +/- 19.1 mg/dl, HDL-c level was 44 +/- 10.3 mg/dl and total cholesterol/HDL-c ratio was 4.64 +/- 1.13. Basal peak aortic jet velocity (Vmax2) was 2.67 +/- 0.39 m/sec, mean pressure gradient (Pmean2) was 15.6 +/- 5.5 mmhg. Annual progression rate in peak aortic jet velocity (Vmax) was 0.23 +/- 0.17 m/sec, in mean pressure gradient (Pmean) was 3 +/- 2.1 mmhg. Annual progression rate in Pmean was most strongly correlated with serum HDL-c level and total/HDL-c ratio (r=-0.528 and 0.505; <0.001 and 0.001 respectively). Progression in Vmax values was positively correlated with serum LDL-c level and total/HDL-c ratio while negatively correlated with serum HDL-c levels (r=0.328, 0.499 and -0.464; P=0.034, 0.001 and 0.002 respectively). Among HDL subspecies HDL2 was the predominant type. HDL2 levels were found to be positively correlated with progression rates. There was no significant correlation between apolipoprotein A1 level and annual progression rate. Serum PON1 activity level was determined to be negatively correlated to doppler echocardiographic progression parameters while HDL related PAF-AH activity was independent of disease progression. CONCLUSION: Present study demonstrated a positive correlation between disease progression and serum total cholesterol/HDL-c ratio. Serum HDL-c level was inversely correlated with hemodynamic progression. The majority of HDL was HDL2 subtype. Among HDL related enzymes PON1 enzyme activity exhibited an inverse correlation with disease progression. PMID- 26885241 TI - Effects of dexmedetomidine versus propofol on SPO2 in children with tetralogy of fallot during anesthesia. AB - OBJECTIVE: To determine effects of DEX versus propofol on saturation of pulse oximetry (SPO2) in children with Tetralogy of Fallot (TOF) during anesthesia. METHODS: 54 children with TOF who planned to receive corrected operation were randomly assigned to two groups: group DEX and group Propofol. Indicators were compared at T0 (immediate induction of anesthesia), T1 (tracheal catheterization), T2 (skin incision), T3 (sternal exposure) and T4 (aortic catheterization). RESULTS: In group DEX, the hear rate (HR) and partial pressure difference between alveolar air and arteries [P(A-a)O2] at T1 were lower than those at T0, while systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and SPO2 at T1 were higher than those at T0, with statistically significant differences (P<0.05, respectively). In the group Propofol, SBP, DBP, MBP and SPO2 at T1 were lower than those at T0, while P(A a)O2 at T1 was higher than that at T0, with statistically significant differences (P<0.05, respectively). There were statistically significant differences in all indicators at T1 between two groups (P<0.05, respectively). The group DEX had lower HR and P(A-a)O2, and higher SBP, DBP, MBP and SPO2 than group Propofol. There were no statistically significant differences in all indicators (except for lower HR) at other points between two groups. CONCLUSION: During induction of anesthesia, DEX was better than propofol to improve alveolar oxygenation, reduce myocardial oxygen consumption, increase arterial oxygen content and induce stable induction in patients with TOF, though they were comparable during maintenance of anesthesia. PMID- 26885242 TI - The evaluation of carotid intima-media thickness and mean platelet volume values and correlation with cardiac functions in obese children. AB - BACKGROUND: Obesity is associated with many risk factors, such as hyperlipidemia, hyperinsulinemia, hypertension and leads to early atherosclerosis. The aim of this study was to investigate the relation of the mean platelet volume (MPV) and the carotid intima media thickness (CIMT) on cardiac functions among obese children. MATERIALS AND METHODS: Sixty obese children, with body mass index percentile were >95% and forty eight healthy controls were enrolled in the study. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), thyroid function tests, hemoglobin, white blood cell, MPV and insulin resistance were evaluated. CIMT was measured by using high-resolution ultrasound and echocardiography was performed to all individuals. RESULTS: MPV and CIMT values were found significantly higher in obese children than controls. There was positive correlation between CIMT and age, body surface area (BSA), systolic and diastolic blood pressure, left ventricular meridional end-systolic wall stress (ESWSm), myocardial fiber stress (MFS), stroke volume (SV) and insulin and negative correlation with left ventricle end-systolic elastance by single beat technique (Ees(sb)) and arterial elastance (Ea). There was no correlation between LVM, cardiac risk profiles and CIMT. Multiple stepwise regression analyses revealed that ESWSm (beta=0.337, P=0.049) was only independent factor on CIMT. MPV values showed negative correlation with ALT, AST, Free T4, thyroid stimulating hormone and positive correlation with age and BSA. CONCLUSION: Current study showed that obesity has an independent impact on CIMT and MPV values in children. Increased CIMT in obese children leads significant increase in ESWSm and decrease in Ea and Ees(sb). PMID- 26885243 TI - The factors affecting early death after the initial therapy of acute myeloid leukemia. AB - There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML. PMID- 26885239 TI - The epidemiology and risk factors of inflammatory bowel disease. AB - This review aimed to summarize the epidemiology (incidence, prevalence and morality) and risk factors of inflammatory bowel disease (IBD). IBD is a chronic, relapsing, inflammatory disorder of the gastrointestinal tract and includes Crohn's Disease (CD) and ulcerative colitis (UC). IBD has increasing incidence and prevalence in most of countries and becomes a global emerging disease. A westernized lifestyle or habits and some environmental factors have been found to contribute to the pathogenesis of IBD. The relevant risk factors include Smoking, hygiene hypothesis, microorganisms, appendectomy, medication, nutrition, and stress have all been found to be associated with the modality of IBD, but results are inconsistent on this issue in available studies. Therefore, more studies are required to identify and understand the environmental determinants of IBD. PMID- 26885245 TI - Association of apneic oxygenation with decreased desaturation rates during rapid sequence intubation by a Chinese emergency medicine service [Retraction]. AB - [This retracts the article on p. 11428 in vol. 8, PMID: 26379959.]. PMID- 26885244 TI - Pilot feasibility research of Chinese version of kidney transplant questionnaire in recipients of living donor kidney transplantation. AB - OBJECTIVE: To explore the feasibility of the Chinese version of Kidney Transplant Questionnaire (KTQ) by evaluating the health-related quality of life (HRQoL) in Chinese recipients of living donor kidney transplantation. METHODS: The English version of KTQ was translated into Chinese and underwent cultural adaptation to obtain the Chinese version of KTQ. HRQoL of 136 Chinese recipients of living donor kidney transplantation that met the inclusion criteria were evaluated to assess the validity and reliability of the questionnaire. RESULTS: One hundred and thirty-six recipients (98 males and 38 females) of living donor kidney transplantation were included. The mean age of the recipients was 43.91 years. For each dimension of the questionnaire, the Cronbach's alpha coefficient was 0.7 0.9, test-retest reliability coefficient >=0.7, goodness of fit index (GFI) >0.9, and comparative fitness index (CFI) >0.9. CONCLUSION: The validity and reliability of the Chinese version of KTQ is similar to the English version, suggesting that the Chinese version of KTQ could be applied as a disease-specific questionnaire to evaluate the HRQoL of the recipients of living donor kidney transplantation in China. PMID- 26885246 TI - Validation of a Reversed-Phase High Performance Liquid Chromatography Method for the Simultaneous Analysis of Cysteine and Reduced Glutathione in Mouse Organs. AB - A depletion of reduced glutathione (GSH) has been observed in pathological conditions and in aging. Measuring GSH in tissues using mouse models is an excellent way to assess GSH depletion and the potential therapeutic efficacy of drugs used to maintain and/or restore cellular redox potential. A high performance liquid chromatography (HPLC) method for the simultaneous determination of GSH and cysteine (Cys) in mouse organs was validated according to USA and European standards. The method was based on separation coupled with ultraviolet detection and precolumn derivatization with 5,5'-dithiobis-(2 nitrobenzoic acid) (DTNB). The required validation parameters, that are, selectivity, linearity, lower limit of quantification, precision, accuracy, recovery, and stability, were studied for spleen, lymph nodes, pancreas, and brain. The results showed that the lower limits of quantification were 0.313 MUM and 1.25 MUM for Cys and GSH, respectively. Intraday and interday precisions were less than 11% and 14%, respectively, for both compounds. The mean extraction recoveries of Cys and GSH from all organs were more than 93% and 86%, respectively. Moreover, the stability of both analytes during sample preparation and storage was demonstrated. The method was accurate, reliable, consistent, and reproducible and it was useful to determine Cys and GSH in the organs of different mouse strains. PMID- 26885247 TI - The Impact of Chronic Tobacco Smoking on Retinal and Choroidal Thickness in Greek Population. AB - Aim. To investigate the effect of more than 25-year cigarette smoking on choroidal and retinal thickness, using spectral domain optical coherence tomography (SD-OCT). Methods. Thirty-one smokers and 25 age- and sex-matched nonsmokers, serving as control group, were submitted to slit-lamp biomicroscopy and dilated fundoscopy, SD-OCT, measurements of intraocular pressure (IOP), central corneal thickness (CCT), and axial length (AL). Heidelberg Spectralis was used to calculate choroidal thickness (CT), ganglion cell complex (GCC), outer retina layers (ORL), and macular thicknesses (MT). Results. The smokers' group consisted of 17 males and 14 females with mean age of 57.8 +/- 4.5 years, while the controls' group consisted of 14 males and 11 females with mean age of 68.0 +/ 4.1 years. CT and GCC thicknesses were significantly reduced in smokers compared to control group. The differences in thicknesses of ORL were marginally significant between two groups. The measurements of MT, IOP, CCT, and AL had the same distributions between smokers and nonsmokers. Conclusions. Tobacco smoking seems to result in thinner choroid and retina compared to nonsmokers. This is the first study in literature that investigates the anatomical effect of smoking for more than 25 years on the choroid and retina. PMID- 26885248 TI - Oxidative Stress Markers in Sputum. AB - Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases. PMID- 26885249 TI - Changes in Oxidative Stress and Antioxidant Enzyme Activities in Streptozotocin Induced Diabetes Mellitus in Rats: Role of Alhagi maurorum Extracts. AB - Alhagi maurorum (camel thorn plant) is a promising medicinal plant due to the presence of flavonoids and phenolic compounds as major contents of its constituents. No previous study has been conducted before on A. maurorum extracts as an antioxidative stress and/or antidiabetic herb in STZ-induced DM in rats. Therefore, four groups of rats were allocated as control (C), STZ-induced DM (D), and STZ-induced DM supplemented with 300 mg/kg BW of either aqueous extract (WE) or ethanolic extract (EE) of A. maurorum. The plasma levels of glucose, TG, TC, LDL-C and VLDL-C, MDA, and bilirubin and the activities of transaminases and GR were significantly increased in the diabetic group. Also, diabetic rats showed severe glucose intolerance and histopathological changes in their livers. In addition, levels of insulin, total proteins, GSH, and HDL-C and the activities of SOD, GPx, and GST were significantly decreased in the diabetic rats compared to those of the control group. The ingestion of A. maurorum extracts lowered the blood glucose levels during the OGTT compared to the diabetic rats and restored all tested parameters to their normal levels with the exception of insulin level that could not be restored. It is concluded that A. maurorum extracts decreased elevated blood glucose levels and hyperlipidemia and suppressed oxidative stress caused by diabetes mellitus in rats. PMID- 26885251 TI - Oxidative Stress Biomarkers and Left Ventricular Hypertrophy in Children with Chronic Kidney Disease. AB - Cardiovascular diseases remain the most frequent cause of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between oxidative stress biomarkers and cardiovascular risk factors and left ventricular hypertrophy in children with CKD. Material and Methods. The studied group consisted of 65 patients aged 1.4-18.6 (mean 11.2) years with stages 1 to 5 CKD. Serum oxidized low-density lipoprotein (oxLDL), protein carbonyl group, creatinine, cystatin C, albumin, lipids, high-sensitivity C-reactive protein, intercellular adhesion molecule-1, insulin, plasma renin activity, and aldosterone levels were measured. Patients were divided into groups depending on CKD stage. Anthropometric measurements, ambulatory blood pressure (BP) measurements, and echocardiography with left ventricular mass (LVM) calculation were performed. Results. Serum oxLDL strongly correlated with creatinine (R = 0.246; p = 0.048), cystatin C (R = 0.346; p = 0.006), total cholesterol (R = 0.500; p < 0.001), triglycerides (R = 0.524; p < 0.001), low density lipoprotein concentrations (R = 0.456; p < 0.001), and 24 hour BP values of systolic (R = 0.492; p = 0.002), diastolic (R = 0.515; p < 0.001), and mean arterial pressure (R = 0.537; p < 0.001). A significant correlation between oxLDL levels and LVM z-scores (R = 0.299; p = 0.016) was found. Conclusions. Hypertension and dyslipidemia correlated with lipid oxidation in children with CKD. oxLDLs seem to be valuable markers of oxidative stress in CKD patients, correlating with left ventricular hypertrophy. PMID- 26885252 TI - Effect of Carnosine in Experimental Arthritis and on Primary Culture Chondrocytes. AB - Carnosine's (CARN) anti-inflammatory potential in autoimmune diseases has been but scarcely investigated as yet. The aim of this study was to evaluate the therapeutic potential of CARN in rat adjuvant arthritis, in the model of carrageenan induced hind paw edema (CARA), and also in primary culture of chondrocytes under H2O2 injury. The experiments were done on healthy animals, arthritic animals, and arthritic animals with oral administration of CARN in a daily dose of 150 mg/kg b.w. during 28 days as well as animals with CARA treated by a single administration of CARN in the same dose. CARN beneficially affected hind paw volume and changes in body weight on day 14 and reduced hind paw swelling in CARA. Markers of oxidative stress in plasma and brain (malondialdehyde, 4-hydroxynonenal, protein carbonyls, and lag time of lipid peroxidation) and also activity of gamma-glutamyltransferase were significantly corrected by CARN. CARN also reduced IL-1alpha in plasma. Suppression of intracellular oxidant levels was also observed in chondrocytes pretreated with CARN. Our results obtained on two animal models showed that CARN has systemic anti-inflammatory activity and protected rat brain and chondrocytes from oxidative stress. This finding suggests that CARN might be beneficial for treatment of arthritic diseases. PMID- 26885250 TI - Relationship between Oxidative Stress, Circadian Rhythms, and AMD. AB - This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed. PMID- 26885253 TI - Morphological and Biochemical Effects on the Skeletal Muscle of Ovariectomized Old Female Rats Submitted to the Intake of Diets with Vegetable or Animal Protein and Resistance Training. AB - Introduction. Sarcopenia is a process characterized by reduction in protein mass and muscle strength with increasing age, especially in the postmenopausal period, resulting in functional limitations and with great impact on the physical autonomy of the elderly. Objective. To evaluate the effects of diets with vegetable proteins (VP) or animal proteins (AP) associated with resistance training (RT) on the structural and biochemical parameters of the medial gastrocnemius muscle in Wistar rats with sarcopenia. Methods. An experimental model with ovariectomized rats was used to induce sarcopenia and resistance training. The histochemical technique was used for the typing of muscle fibers, the cross-sectional area of myocytes, and volume densities of myocytes and interstitium; the technique of Picrosirius stain was used to highlight the collagen fibers. Results. The VP diet was not able to minimize the effects of sarcopenia in the medial gastrocnemius of sedentary animals and when associated with RT, it promoted maintenance of the CSA, attenuating the atrophy of type IIB fibers in the medial gastrocnemius. The AP diet in sedentary animals protected the type I fibers. When combined with RT, the AP promoted muscle remodeling, with reduction in volume density of type I and IIA fibers, and increase of IIB fibers, together with an increase in collagen volume density. Conclusion. The data suggest a tendency to better results of hypertrophy in animal groups that consumed the AP diet, even the sedentary animals, although more evident in those trained. PMID- 26885255 TI - New insights into MicroRNAs involves in drug resistance in diffuse large B cell lymphoma. AB - Diffuse large B cell lymphoma (DLBCL) accounts for nearly 40% of non-Hodgkin's lymphoma cases. The combined chemotherapy of rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone (R-CHOP) is considered as the standard therapy for DLBCL; however, nearly half of the patients become refractory to the R-CHOP regimen. Early identification of drug resistance and therapeutic failures are crucial for the identification of high-risk patients. MicroRNAs (miRNAs) are a group of small and non-coding RNAs negatively regulating gene expression through binding to their target mRNAs. Recent studies demonstrated that miRNAs are involved in chemotherapeutic drug resistance in tumor. In our review, we summarize the current evidence on the role of miRNAs in the prediction and modulation of cellular response to rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone in DLBCL. PMID- 26885254 TI - Potential mechanisms underlying the Runx2 induced osteogenesis of bone marrow mesenchymal stem cells. AB - Bone marrow derived mesenchymal stem cells (BM-MSCs) belong a type of pluripotent stem cells and can be induced to differentiate into osteoblasts (OB). Runt related transcription factor 2 (Runx2) is an osteogenesis specific transcription factor and plays an important role in osteogenesis of BM-MSCs. It can promote the expression of osteogenesis related genes, regulate cell cycle progression, improve bone microenvironment and affect functions of chondrocytes and osteoclasts, which have involvement of a large amount of signal molecules including TGF-beta, BMP, Notch, Wnt, Hedgehog, FGF and microRNA. In this paper, we summarize the mechanisms underlying the Runx2 induced osteogenesis of BM-MSCs. PMID- 26885256 TI - Extracorporeal shock wave therapy effectively prevented diabetic neuropathy. AB - BACKGROUND: We tested the hypothesis that extracorporeal shock wave (ECSW) therapy can effectively protect sciatic nerve (SN) from diabetes mellitus (DM) induced neuropathy in leptin-deficient (ob/ob) mice. METHODS AND RESULTS: Eighteen-week C57BL/6 mice (n=8) served as age-matched controls (group 1) and ob/ob mice (n=16) were categorized into DM (group 2) and DM + ECSW (0.12 mJ/mm(2) for 4 times of 200 impulses at 3-week intervals) (group 3). The animals were sacrificed two weeks post-ECSW. In vitro results showed that the protein expressions of oxidative stress (NOX-1, NOX-2, oxidized protein), inflammation (MMP-9, TNF-alpha, iNOS), apoptosis (Bax, cleaved caspase-3, & PARP), and DNA damage marker (gamma-H2AX) were significantly higher in RT4-D6P2T (schwannoma cell line) treated by menadione (25 uM) compared with control group and were significantly reversed after ECSW (0.12 mJ/mm(2), 200 impulses) (all p<0.001). mRNA expressions of inflammation (MMP-9, TNF-alpha, iNOS), oxidative stress (NOX 1, NOX-2) and apoptosis (Bax, caspase-3) in SN were significantly higher in group 2 than in group 1 and were significantly reversed in group 3, whereas the mRNA expressions of anti-oxidants (HO-1, NQO1) progressively increased from group 1 to group 3 (all p<0.001). Cellular expressions of F4/80+, CD14+, gamma-H2AX+ cells, and number of vacuolar formation in SN showed a pattern identical to that of inflammation markers among all groups (all p<0.001). Microscopic findings of Schwann cells and myelin-sheath scores, and number of eNOS+ cells in SN showed a reversed pattern compared to that of inflammation among all groups (all p<0.001). CONCLUSIONS: ECSW therapy protected SN against DM-induced neuropathy. PMID- 26885257 TI - Sustained release poly (lactic-co-glycolic acid) microspheres of bone morphogenetic protein 2 plasmid/calcium phosphate to promote in vitro bone formation and in vivo ectopic osteogenesis. AB - Bone regeneration often requires continuous stimulation to promote local bone formation. In the present study, calcium phosphate (CaPi) was used to promote transfection of human bone morphogenetic protein 2 (BMP-2) cDNA plasmid, and poly (lactic-co-glycolic acid) (PLGA) was used to prepare microspheres of pBMP-2/CaPi (i.e., PLGA@pBMP-2/CaPi) using W/O/W double emulsion solvent evaporation method. We showed that PLGA@pBMP-2/CaPi microspheres were spherical with smooth surface, and the particle size ranged from 0.5 to 35 MUm. Encapsulation efficiency was up to 30~50%. The release of BMP-2 cDNA from microspheres continued more than 30 days and constituted, less than 7.5% of total plasmid amount within the first 24 h. Real-time PCR results showed that co-culturing of PLGA@pBMP-2/CaPi with bone marrow-derived mesenchymal stem cells (BMSCs) increased calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7, and collagen type I (COLL I) in a time-dependent manner. Finally, X-ray analysis demonstrated that in vivo delivery of PLGA@pBMP-2/CaPi microspheres into the tibialis anterior muscles of rats promoted the generation of osteoblasts, bone tissue, and bone structure. The findings suggested that PLGA@pBMP-2/CaPi microspheres can promote ectopic osteogenesis in non-bone tissues, with strong prospects in promoting bone regeneration. PMID- 26885258 TI - Dioclea violacea lectin ameliorates oxidative stress and renal dysfunction in an experimental model of acute kidney injury. AB - Acute kidney injury (AKI) is characterized by rapid and potentially reversible decline in renal function; however, the current management for AKI is nonspecific and associated with limited supportive care. Considering the need for more novel therapeutic approaches, we believe that lectins from Dioclea violacea (Dvl), based on their anti-inflammatory properties, could be beneficial for the treatment of AKI induced by renal ischemia/reperfusion (IR). Dvl (1 mg/kg, i.v.) or vehicle (100 uL) was administered to Wistar rats prior to the induction of bilateral renal ischemia (45 min). Following 24 hours of reperfusion, inulin and para-aminohippurate (PAH) clearances were performed to determine glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF) and renal vascular resistance (RVR). Renal inflammation was assessed using myeloperoxidase (MPO) activity. Kidney sections were stained with hematoxylin-eosin to evaluate morphological changes. Intracellular superoxide anions, hydrogen peroxide, peroxynitrite, nitric oxide and apoptosis were analyzed using flow cytometry. IR resulted in diminished GFR, RPF, RBF, and increased RVR; however, these changes were ameliorated in rats receiving Dvl. AKI-induced histomorphological changes, such as tubular dilation, tubular necrosis and proteinaceous casts, were attenuated by Dvl administration. Treatment with Dvl resulted in diminished renal MPO activity, oxidative stress and apoptosis in rats submitted to IR. Our data reveal that Dvl has a protective effect in the kidney, improving renal function after IR injury, probably by reducing neutrophil recruitment and oxidative stress. These results indicate that Dvl can be considered a new therapeutic approach for AKI-induced kidney injury. PMID- 26885259 TI - The non-Geldanamycin Hsp90 inhibitors enhanced the antifungal activity of fluconazole. AB - The molecular chaperone heat shock protein 90 (Hsp90) is highly conserved in eukaryotes and facilitates the correct folding, productive assembly and maturation of a diverse cellular proteins. In fungi, especially the most prevalent human fungal pathogen Candida albicans, Hsp90 influences development and modulates drug resistance. Here, we mainly explore the effect of non Geldanamycin Hsp90 inhibitor HSP990 on the activity of fluconazole (FLC) against Candida albicans and investigate the underlying mechanism. We demonstrate that HSP990 has potent synergistic antifungal activity with FLC against FLC-resistant C. albicans through the checkerboard microdilution assay,agar diffusion tests and time-kill curves, and shows low cytotoxicity to human umbilical vein endothelial cells. Further study shows that the activity of FLC against C. albicans biofilm formation in vitro is significantly enhanced when used in combination with HSP990. In a murine model of disseminated candidiasis, the therapeutic efficacy of FLC is also enhanced by the pharmacological inhibition of C. albicans Hsp90 function with HSP990. Thus, the combined use of small molecule compound and existing antifungal drugs may provide a potential therapeutic strategy for fungal infectious disease. PMID- 26885260 TI - Later phase cardioprotection of ischemic post-conditioning against ischemia/reperfusion injury depends on iNOS and PI3K-Akt pathway. AB - BACKGROUND: The cardioprotection of ischemic post-conditioning (IPO) has been well demonstrated after a short period of reperfusion. However, little is known about the long-term effects of IPO. This study aimed to investigate the long term cardioprotection of IPO in a rat myocardial ischemia/reperfusion model and to explore the potential mechanism. METHODS AND RESULTS: Rats were either sham operated (Sham group) or underwent 30-min left anterior descending coronary artery ischemia followed by immediate reperfusion (I/R group) or post conditioning with 5 cycles of 10-s ischemia and 10-s reperfusion (IPO group). At 24 h after reperfusion, infarct size reduced from 34.7+/-1.1% in I/R group to 24.9+/-1.3% in IPO group (P<0.05) and the iNOS expression in IPO group was 4.7 fold higher than in I/R group. iNOS inhibitor 1400 W (1 mg/kg, 5 min before postconditioning or reperfusion) prevented the increase in iNOS expression and abolished IPO-induced protection (34.4+/-1.0%, P>0.05 vs. I/R group). When rats were treated with PI3K inhibitor LY294002 5 min before reperfusion (0.3 mg/kg), p Akt expression at R 3 h and iNOS expression at R 24 h were significantly inhibited. Moreover, the delayed infarct-sparing effect of IPO was absent in the presence of LY294002. CONCLUSION: IPO has prolonged cardioprotective effects and iNOS as an important downstream effector of PI3K-Akt pathway contributes to the delayed phase cardioprotection of IPO. PMID- 26885261 TI - A novel method in preparation of acellularporcine corneal stroma tissue for lamellar keratoplasty. AB - Our objective was to develop a novel lamellar cornealbiomaterial for corneal reconstruction.Theporcine acellular corneal stroma discs (ACSDs) were prepared from de-epithelized fresh porcine corneas (DFPCs) by incubation with 100% fresh human serum and additional electrophoresis at 4 degrees C. Such manipulation removed theanterior corneal stromal cells without residual of DNA content and alpha-Galantigen. Human serum decellularizing activity on porcineanterior corneal stroma cells is through apoptosis, and associated with the presence of alpha-Gal epitopes in anterior stroma. ACSDs displayed similar optical, biomechanical properties and ultrastructure to DFPCs, and showed good histocompatibility in rabbit corneal stromal pockets and anterior chamber. Rabbit corneallamellar keratoplasty (LKP) using ACSDs showed no rejection and high transparency of cornea at 2 months after surgery. In vivo confocal laser scanning microscopy and immunostaining analysis showed complete re-epithelization and stromal cell in growth of ACSDs without inflammatory cell infiltration, new blood vessel ingrowth and excessive wound healing. In conclusion, this novel decellularization method may be valuable for preparation of xenogenic corneal tissue for clinical application, ACSDs resulted from this method may be served as a matrix equivalent for LKP in corneal xenotransplantation. PMID- 26885262 TI - The role of 1,25-dyhydroxyvitamin D3 in mouse liver ischemia reperfusion injury: regulation of autophagy through activation of MEK/ERK signaling and PTEN/PI3K/Akt/mTORC1 signaling. AB - Autophagy is an important mechanism for cellular homeostasis and survival during pathologic stress conditions in the liver, such as ischemia-reperfusion injury. In this study, we hypothesized a protective role of vitamin Din hepatic IR model. The administration of vitamin D displayed significantly preserved liver function as characterized by less histological damage and reduced serum enzymes level. We found that the protective effect was associated with ameliorated oxidative stress as manifested by the increase of antioxidant capacity and decrease of lipid peroxidation. Further, increased autophagic flux after vitamin D administration was demonstrated by the increase of protein light chain 3 (LC3) conversion both in vivo and in vitro. MEK/ERK and PTEN/PI3K/Akt/mTOR were both found critically involved in vitamin D-induced autophagy. By employing intracellular ROS and cell viability assay, we further confirmed this hypothesis with the observation that inhibition either of the MEK/ERK or PTEN/PI3K/Akt/mTOR pathway partly abolished the protective effect of vitamin D-induced autophagy, while inhibiting initiation of autophagy signaling pathway by knockdown of Beclin-1 completely reversed the protection provided by vitamin D. Collectively, the present results indicate that the protective role of vitamin D in murine hepatic IR injury is autophagy dependent, which is regulated by both MEK/ERK and PTEN/PI3K/Akt/mTOR pathway. PMID- 26885263 TI - B7-H3 expression associates with tumor invasion and patient's poor survival in human esophageal cancer. AB - B7-H3, a member from B7-family co-stimulatory ligands, plays an important role in adaptive immune responses. In addition, recent studies also demonstrated that B7 H3 could be highly expressed in various types of human cancers, and its expression level was significantly associated with cancer patients' clinicopathological parameters and postoperative prognoses. As of now, the exact role of B7-H3 expression in human esophageal cancer still remains elusive. In the present study, we characterized the B7-H3 expression in the human esophageal cancer cell line Eca-109 and TE-1, and in 174 cases of human esophageal cancer tissues, and to analyze its clinical implications and its correlation to T cell infiltration. By using the RNA interference method to down-regulate the B7-H3 expression in human esophageal cancer cell line Eca-109, we further studied the contribution of high B7-H3 expression to the biological features of this malignancy. Our results showed that B7-H3 was highly expressed in the cell line Eca-109 and TE-1, the high expression level of B7-H3 in esophageal cancer tissues was significantly associated with tumor invasion and patient's poor survival. Moreover, the higher B7-H3 expression was significantly and inversely correlated to the CD3(+)T cells infiltration in tumor nest of esophageal cancer tissues. We successfully constructed the recombinant lentivirus of siRNA targeting B7-H3, and the cellular studies showed that the down regulation of B7-H3 expression could suppress the proliferation, colony formation, migration and invasion in Eca-109 cells, which was consistent with the finding from the clinical sample cohort study. Collectively, the high B7-H3 expression was involved in the cancer progression of human esophageal cancer, and might contributed to the negative regulation of T-cell mediated antitumor response in tumor microenvironment, and the proliferation and mobility of esophageal cancer cells. The detailed mechanism and the potential value of clinical use targeting B7-H3 against human esophageal cancer merit further investigation. PMID- 26885264 TI - Up-regulation of microRNA-135a protects against myocardial ischemia/reperfusion injury by decreasing TXNIP expression in diabetic mice. AB - BACKGROUND AND AIMS: The heart in diabetic state is sensitive to myocardial ischemia reperfusion (mI/R) injury. In the present study, we investigated the potential mechanisms of modulating mI/R injury in diabetic state. METHODS: Diabetic db/db mice and control non-diabetic mice were administrated with mI/R injury or sham operation. Mouse atrial-derived cardiac cell line HL-1 subjected to hypoxia-reoxygenation (H/R) was used as in vitro model of I/R injury to the heart. RESULTS: Compared with normal mice, mI/R elevated the levels of myocardial infarct size, apoptosis and TXNIP expression (in mRNA and protein) in diabetic mice. Myocardial miR-135a expression level was reduced in diabetic mice regardless of mI/R treatment or not. MiR-135a overexpression protected myocardial cells from mI/R injury in diabetic mice. In vitro, high glucose incubation contributed to a significant down-regulation of miR-135a and up-regulation of TXNIP in cells with or without H/R treatment. Luciferase reporter assay showed that TXNIP was a target gene of miR-135a. MiR-135a overexpression protected HL-1 cells from H/R injury in high glucose condition, while this effect was reversed by up-regulated TXNIP. CONCLUSION: miR-135a protects against mI/R injury by decreasing TXNIP expression in diabetic state. PMID- 26885265 TI - Anti-inflammatory and anti-apoptotic effects of oxysophoridine on lipopolysaccharide-induced acute lung injury in mice. AB - Oxysophoridine (OSR) is an alkaloid with multiple pharmacological activities. This study aimed to investigate the protective effects and underlying mechanisms of OSR on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Here, we found that OSR treatment markedly mitigated LPS-induced body weight loss and significant lung injury characterized by the deterioration of histopathology, histologic scores, wet-to-dry ratio, exduate volume, and protein leakage. OSR dramatically attenuated LPS-induced lung inflammation, as evidenced by the reduced levels of total cells, neutrophils, lymphocytes, and macrophages and pro inflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin (IL) 1beta, IL-6, and monocyte chemoattractant protein-1) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. OSR also inhibited LPS induced expression and activation of nuclear factor-kappaB p65 in pulmonary tissue. Additionally, OSR administration markedly prevented LPS-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase 8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that OSR is a potential therapeutic drug for treating LPS-induced ALI. PMID- 26885266 TI - Acceleration of diabetic wound healing by a cryopreserved living dermal substitute created by micronized amnion seeded with fibroblasts. AB - Bioengineered dermal substitutes have been used for the treatment of diabetic ulcers in clinics and achieved satisfactory results. However, constructing traditional tissue engineered dermal substitutes with two-step method is high cost, time-consuming and greatly decreases fibroblast proliferative activity because of repeated trypsinization. Inthisstudy, we created a 3D micronized amniotic membrane (mAM) and used it as a natural microcarrier for ex vivo culture and amplification of human dermal fibroblasts (HDF) combined with the rotary cell culture system (RCCS). This one-step mAM-RCCS method couldamplify HDF quickly and construct a dermal substitute HDF-mAM simultaneously. To facilitate the clinical application of mAM-RCCS, anoptimized storage method was used.Post-thawing HDF-mAM retained high cell viability, intact cell morphology and active peptide secretion. When transplanted to the wounds of db/db mice, cryopreserved HDF-mAM promoted vascularization and diabetic wound healing significantly. These results demonstrate the potential application of cryopreserved HDF-mAM as a living dermal substitutefor treating diabetic ulcers and other chronic wounds in clinics. PMID- 26885267 TI - Adipocytes exert lipotoxic effects on osteoblast through activating hypoxia signaling pathway in vitro. AB - This study aimed to investigate the effect of adipocytes on osteoblastic bone formation in vitro. The differentiated and undifferentiated 3T3-L1 cells were co cultured with primary calvarial osteoblasts. At 48 h, proliferated osteoblasts decreased significantly after co-culture with differentiated preadipocytes as compared to those co-cultured with undifferentiated preadipocytes; at 7 days, the expressions of bone formation-related genes decreased in osteoblasts co-cultured with differentiated preadipocytes; at 14 days, osteoblasts mineralization also decreased significantly after co-culture with differentiated preadipocytes. To further determine whether the decreased proliferation and mineralization were related to the hypoxia signaling pathway, the expressions of hypoxia related genes were detected. Results showed the expressions of these genes significantly increased after co-culture with differentiated preadipocytes. NF-kappaB and IL-6 expressions were also up-regulated in osteoblasts co-cultured with differentiated preadipocytes. Osteoblasts from Hif1alpha(f/f) mice showed increased proliferation and mineralization after co-culture with adipocytes transfected with adenoviral-cre, accompanied by up-regulated expressions of bone formation related genes and down-regulated expressions of NF-kappaB and IL-6. These results demonstrated that adipocytes exert a negative effect on the proliferation and mineralization of osteoblasts via up-regulating the expressions of hypoxia related genes, and NF-kappaB and IL-6 may impair the osteoblastic bone formation. PMID- 26885268 TI - Protective effect of carnosine after chronic cerebral hypoperfusion possibly through suppressing astrocyte activation. AB - AIM: Subcortical ischemic vascular dementia (SIVD) induced by chronic hypoperfusion is a common cause of vascular dementia. The aim of this study was to determine whether the protective effect of carnosine on white matter lesion after chronic cerebral hypoperfusion through suppressing astrocyte activation. METHODS: Adult male mice (C57BL/6 strain) were subjected to permanent occlusion of the right unilateral common carotid arteries (rUCCAO) and treated with carnosine or histidine. Open field test, freezing test, Kluver-Barrera staining, immunohistochemical analyses and western blot were performed after rUCCAO. RESULTS: We found that carnosine ameliorated white matter lesion and cognitive impairment after rUCCAO. Carnosine suppressed the activation of astrocyte in both wide type mice and histidine decarboxylase knockout mice. However, administration of histidine did not show the same effect. We found that there were no differences between rUCCAO group and sham group for the expression of glutamate transporter-1 (GLT-1) and glutamate/aspartate transporter (GLAST). Furthermore, carnosine significantly attenuated the increase of inflammatory cytokine interferon gama. CONCLUSION: These data suggest carnosine induced neuroprotection during SIVD in mice is not dependent on the histaminergic pathway or the regulation of the expression of GLT-1 and GLAST, but may be due to a suppression of astrocyte activation and inflammatory cytokine release. PMID- 26885269 TI - Overexpression of miR-506 inhibits growth of osteosarcoma through Snail2. AB - Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis accounts for the majority of OS-related death. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Thus, elucidation of the involvement of specific miRNAs in the metastasis of OS may provide novel therapeutic targets for OS treatment. Here, we showed that in the OS specimens from patients, the levels of miR-506 were significantly decreased and the levels of Snail2 were significantly increased, compared to the paired normal bone tissue. MiR-506 and Snail2 inversely correlated in patients' specimen. Bioinformatics analyses predicted that miR-506 may target the 3'-UTR of Snail2 mRNA to inhibit its translation, which was confirmed by luciferase-reporter assay. Moreover, miR-506 overexpression inhibited Snail2-mediated cell invasiveness, while miR-506 depletion increased Snail2-mediated cell invasiveness in OS cells. Together, our data suggest that miR-506 suppression in OS cells may promote Snail2-mediated cancer metastasis. PMID- 26885271 TI - Cardiosphere-derived cell sheet primed with hypoxia improves left ventricular function of chronically infarcted heart. AB - Cardiosphere-derived cells (CDCs) isolated from postnatal heart tissue are a convenient and efficientresource for the treatment of myocardial infarction. However, poor retention of CDCs in infarcted hearts often causes less than ideal therapeutic outcomes. Cell sheet technology has been developed as a means of permitting longer retention of graft cells, and this therapeutic strategy has opened new avenues of cell-based therapy for severe ischemic diseases. However, there is still scope for improvement before this treatment can be routinely applied in clinical settings. In this study, we investigated whether hypoxic preconditioning enhances the therapeutic efficacy of CDC monolayer sheets. To induce hypoxia priming, CDC monolayer sheets were placed in an incubator adjusted to 2% oxygen for 24 hours, and then preconditioned mouse CDC sheets were implanted into the infarcted heart of old myocardial infarction mouse models. Hypoxic preconditioning of CDC sheets remarkably increased the expression of vascular endothelial growth factor through the PI3-kinase/Akt signaling pathway. Implantation of preconditioned CDC sheets improved left ventricular function inchronically infarcted hearts and reduced fibrosis. The therapeutic efficacy of preconditioned CDC sheets was higher than the CDC sheets that were cultured under normaxia condition. These results suggest that hypoxic preconditioning augments the therapeutic angiogenic and anti-fibrotic activity of CDC sheets. A combination of cell sheets and hypoxic preconditioning offers an attractive therapeutic protocol for CDC transplantation into chronically infarcted hearts. PMID- 26885270 TI - Over-expression of HSPA12B protects mice against myocardium ischemic/reperfusion injury through a PPARgamma-dependent PI3K/Akt/eNOS pathway. AB - Acute myocardial ischemia/reperfusion (MIR) injury leads to severe arrhythmias and a high lethality. We aim to determine the effect of heat shock protein A12B (HSPA12B), a newly discovered member of the Hsp70 family, on heart injury parameters following MIR surgery. We used HSPA12B transgenic mice to determine its effects on heart function parameters, infarct size and cellular apoptosis following MIR surgery. Proinflammatory cytokines, oxidative products and anti oxidative enzymes in the myocardium were measured to evaluate the anti inflammatory and anti-oxidative effects of HSPA12B over-expression. The role of PPARs/eNOS/PI3k/Akt pathway was investigated using their inhibitors. The alteration of hemodynamic parameters, histopathological, apoptotic and infarct size caused by MIR was greatly attenuated in HSPA12B over-expressed mice. HSPA12B also greatly mitigated the inflammatory response, demonstrated by the decrease in the levels of IL-1beta, IL-6, TNF-a and MPO. Anti-oxidative enzymes (SOD, Catalase and GPx) were restored by HSPA12B; oxidative products (8-OHdG, MDA and protein carbonyl) were decreased. HSPA12B activated the PPARgamma-dependent eNOS/PI3k/Akt pathway, and the influence of HSPA12B on cardiac function was reversed by the inhibitors of eNOS, PPARgamma, Akt and PI3K. Our results present a novel signaling mechanism that HSPA12B protects MIR injury through a PPARgamma dependent PI3K/Akt/eNOS pathway. PMID- 26885272 TI - c9, t11- conjugated linoleic acid induces HCC cell apoptosis and correlation with PPAR-gamma signaling pathway. AB - OBJECTIVE: Cis9, trans11 conjugated linoleic acid (c9, t11-CLA.) is one of the most important isomers of conjugated linoleic acid, which have a strong anti tumor effects. Based on previous studies, we further explored the molecular mechanism of inducing cells apoptosis in human hepatocellular carcinoma cell line HepG2 and Hep3B. METHODS: Cell Counting Kit 8 (CCK-8) assay was used to investigate the effects of c9, t11-CLA on cell viability and cell proliferation ability; The effects of c9, t11-CLA on cell apoptosis was analyzed by DNA ladder assay, immuno-fluorescence and flow cytometry, respectively. Apoptotic related gene (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bax, Bak, Bad, Bid and Bim), PPAR family member (PPAR-alpha, PPAR-beta and PPAR-gamma), and Cox2 mRNA and protein expression were analyzed by RT-PCR and western blotting. ELISA assay was used to detect the content of Caspase-3. RESULTS: Our data were confirmed that c9, t11 CLA could inhibit the HCC cells proliferation ability and decrease the cells viability. RT-PCR and western blotting assay verified that c9, t11-CLA obviously increased the transcription and protein expression levels of PPAR-gamma. The synchronism and correlation between PPAR-gamma and apoptotic proteins Bcl-2, Bax and Caspase-3 were found with a dose- and time-dependent manner. PPAR-gamma inhibitor GW9662 and activator Rosilitazone were further verified that there was cooperative relation between them. CONCLUSION: In our study, we first report that c9, t11-CLA induces apoptosis in HCC cells by activation of PPARgamma-Bcl-2 Caspase-3 signal pathway. These results indicated that c9, t11-CLA will be useful for clinic therapy of anti-tumor and as a new regulator of PPAR-gamma in the future. PMID- 26885273 TI - TGF-beta1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling. AB - The vascular smooth muscle cell (VSMC) phenotypic switch is considered to be the key pathophysiological change in various cardiovascular diseases, such as aortic dissection, atherosclerosis, and hypertension. The results in this study showed that TGF-beta1 promotes the proliferation, migration and morphological changes of VSMC.TGF-beta1 promoted the expressions of PI3K, P-PI3K, AKT, P-AKT, ID2, and OPN protein and suppressed the expressions of alpha-SMA and SM22alpha protein; the opposite results were observed for TGF-beta1 inhibitor group, AKT inhibitor group and Combined inhibitors group. After the stimulation of TGF-beta1 signaling, the mRNA levels of PI3K, AKT, ID2, and OPN were the highest, while the mRNA levels of alpha-SMA and SM22alpha were the lowest; the opposite results were found in the same groups above. These results suggested the PI3K/AKT/ID2 signaling pathway is involved in TGF-beta1-mediated human aortic VSMC phenotypic switching, that is from a contractile to synthetic phenotype, and Combined inhibitors was more effective in inhibiting the phenotypic switch than a single inhibitor. The Combined inhibitors experiments may provide new avenues for the prevention and treatment of thoracic aortic dissection (TAD) that are based on the pathological effects of phenotypic switching. PMID- 26885274 TI - miR-451 regulates FoxO3 nuclear accumulation through Ywhaz in human colorectal cancer. AB - BACKGROUND AND OBJECTIVE: Our previous studies reported that miR-451 could protect against erythroid oxidant stress target gene-Ywhaz (14-3-3zeta) via inhibiting FoxO3 in the erythropoiesis. This study aimed to investigate the potential mechanism underlying the regulatory effect of miR-451 on human colorectal cancer (CRC) cells. METHODS: In this study, expressions of miR-451 and Ywhaz in CRC tissues and adjacent normal tissues were detected by quantitative real-time PCR (qRT-PCR) and immunohistochemistry respectively. Human colon cancer cell lines were transfected with miR-451-MSCV-PIG retroviral vector to restore miR-451 expression. Ywhaz-3'UTR luciferase reporter assay confirmed Ywhaz as a direct target gene of miR-451. HCT116 cells and H29 cells were transfected with shRNA-Ywhaz (pSGU6-Ywahz-shRNA-GFP) and the protein level of FoxO3 in the nucleus and cytoplasm was detected via Western blot assay. The anti-tumor effects of miR 451 were further verified in nude mice. RESULTS: miR-451 was significantly down regulated in human colon cancer tissues and cell lines (HCT116 and HT29), and inversely correlated with Dukes stage of colon cancer. Ywhaz was a candidate target gene of miR-451 and able to stimulate tumor growth via binding to FoxO3, inhibiting the FoxO3 nuclear accumulation. CONCLUSION: miR-451 may inhibit the colon cancer growth in vitro and in vivo, likely through directly targeting Ywhaz and indirectly regulating the nuclear accumulation of FoxO3. PMID- 26885275 TI - Decrement of miR-199a-5p contributes to the tumorigenesis of bladder urothelial carcinoma by regulating MLK3/NF-kappaB pathway. AB - Aberrant miRNA expression is implicated in tumorigenesis. However, the role of miRNAs in bladder urothelial carcinoma still remains largely unknown. In this study, miR-199a-5p was validated to be significantly down-regulated in bladder urothelial carcinoma. In addition, restoring expression of miR-199a-5p inhibited the tumorigenesis of bladder urothelial carcinoma in vitro and in vivo by inducing the apoptosis and suppressing the proliferation of bladder cancerous cells. Further investigation reported that MLK3 was a direct target of miR-199a 5p. Moreover, the expression level of miR-199a-5p was conversely correlated with MLK3 in bladder cancerous cells. In addition, reintroduction of MLK3 was identified to promote the proliferation and inhibit the apoptotic rate of cells, which have been altered by miR-199a-5p through activating the NF-kappaB pathway. All together, decrement of miR-199a-5p contributes to the tumorigenesis of bladder cancer by directly regulating MLK3/NF-kappaB pathway and miR-199a-5p might be developed as a therapeutic target for treatment of the bladder urothelial carcinoma. PMID- 26885276 TI - Neurochemical abnormalities in anterior cingulate cortex on betel quid dependence: a 2D (1)H MRS investigation. AB - The effects of betel quid dependence (BQD) on biochemical changes remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered neurochemicals in Magnetic Resonance Spectroscopy Imaging (MRSI) and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an 2D (1)H-MRS study to observe brain biochemical alterations in the anterior cingulated cortex (ACC) associated with the severity of BQD and duration of BQD. In the bilateral ACC, our study found NAA/Cr were lower in BQD individuals compared to the healthy controls, Cho/Cr and Glx/Cr were higher in individuals with BQD compared to the healthy group, but increase was noted for mI/Cr in BQD individuals only in the left ACC. NAA/Cr ratios of the right ACC negatively correlated with BQDS and duration, NAA/Cr ratios of the left ACC negatively correlated with duration, Glx/Cr ratios of the right ACC positively correlated with BQDS. The findings of the study support previous analyses of a role for ACC area in the mediation of BQ addiction and mechanistically explain past observations of reduced ACC grey matter in BQD patients. These data jointly point to state related abnormalities of BQ effect and provide a novel strategy of therapeutic intervention designed to normalize Glu transmission and function during treating BQ addiction. PMID- 26885277 TI - BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF beta1. AB - Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-beta1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-beta1. Forced overexpression of BAG3 selectively increased collagens. TGF-beta1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins. PMID- 26885278 TI - Characterization of arginine kinase, anovel allergen of dermatophagoides farinae (Der f 20). AB - OBJECTIVE: To characterize a novel allergen, the Dermatophagoides farinae-derived arginine kinase (Der f 20). METHODS: The protein of Der f 20 was synthesized by genetic engineering approaches. The allergenicity of Der f 20 was tested by enzyme-linked immunosorbent assay and an airway allergy mouse model. RESULTS: The Der f 20 gene was cloned andpresented in the Gene Bank with an accession number of AAP57094. The Der f 20 is an arginine kinase (AK), whichshowed a close relationship with D. pteronyssinus AK and Aleuroglyphusovatus AK. Western-blot and ELISA studies showed the IgE binding capacity of Der f 20 was 66.7% in the sera from 6 dust mite allergic patients. Immune inhibition assayresults showed the IgE cross-reactivity between Der f 20 and DME (Dust mite extract). Positive responses to Der f 20 were 41.2% as shown by skin prick tests in 17 DME-allergic patients. In vitro experimental results showed that Der f 20 induced Th2 cell differentiation and the expression of T cell Ig mucin domain molecule-4 (TIM4) in DCs. Conclusions; The Der f 20 protein is a novel subtype of thedust mite allergen. PMID- 26885279 TI - Chronic Subdural Hematoma in the Aged, Trauma or Degeneration? AB - Chronic subdural hematomas (CSHs) are generally regarded to be a traumatic lesion. It was regarded as a stroke in 17th century, an inflammatory disease in 19th century. From 20th century, it became a traumatic lesion. CSH frequently occur after a trauma, however, it cannot occur when there is no enough subdural space even after a severe head injury. CSH may occur without trauma, when there is sufficient subdural space. The author tried to investigate trends in the causation of CSH. By a review of literature, the author suggested a different view on the causation of CSH. CSH usually originated from either a subdural hygroma or an acute subdural hematoma. Development of CSH starts from the separation of the dural border cell (DBC) layer, which induces proliferation of DBCs with production of neomembrane. Capillaries will follow along the neomembrane. Hemorrhage would occur into the subdural fluid either by tearing of bridge veins or repeated microhemorrhage from the neomembrane. That is the mechanism of hematoma enlargement. Trauma or bleeding tendency may precipitate development of CSH, however, it cannot lead CSH, if there is no sufficient subdural space. The key determinant for development of CSH is a sufficient subdural space, in other words, brain atrophy. The most common and universal cause of brain atrophy is the aging. Modifying Virchow's description, CSH is sometimes traumatic, but most often caused by degeneration of the brain. Now, it is reasonable that degeneration of brain might play pivotal role in development of CSH in the aged persons. PMID- 26885280 TI - Predictor and Prognosis of Procedural Rupture during Coil Embolization for Unruptured Intracranial Aneurysm. AB - OBJECTIVE: The objectives of this study was to determine the incidence and outcomes of procedural rupture (PR) during coil embolization of unruptured intracranial aneurysm (UIA) and to explore potential risk factors. METHODS: This retrospective study evaluated 1038 patients treated with coil embolization between January 2001 and May 2013 in a single tertiary medical institute. PR was defined as evidence of rupture during coil embolization or post procedural imaging. The patient's medical records were reviewed including procedure description, image findings and clinical outcomes. RESULTS: Twelve of 1038 (1.1%) patients showed PR. Points and time of rupture were parent artery rupture during stent delivery (n=2), aneurysm rupture during filling stage (n=9) and unknown (n=1). Two parent artery rupture and one aneurysm neck rupture showed poor clinical outcomes [modified Rankin Scale (mRs) >2] Nine aneurysm dome rupture cases showed favorable outcomes (mRS <=2). Location (anterior cerebral artery) of aneurysm was associated with high procedural rupture rate (p<0.05). CONCLUSION: The clinical course of a patientwith procedural aneurysm rupture during filling stage seemed benign. Parent artery and aneurysm neck rupture seemed relatively urgent, serious and life threatening. Although the permanent morbidity rate was low, clinicians should pay attention to prevent PR, especially when confronting the anterior cerebral artery aneurysm. PMID- 26885282 TI - Endovascular Treatment of Dural Arteriovenous Fistulas: Single Center Experience. AB - OBJECTIVE: Treatment of intracranial dural arteriovenous fistulas (dAVFs) remains a challenge. However, after introduction of Onyx, transarterial approach is the preferred treatment option in many centers. We report our experience of dAVFs embolization with special emphasis on transarterial approach. METHODS: Seventeen embolization procedures were performed in 13 patients with dAVFs between Jan 2009 and Oct 2014. Clinical symptoms, location and type of fistulas, embolization methods, complications, radiological and clinical outcomes were evaluated using charts and PACS images. RESULTS: All 13 patients had symptomatic lesions. The locations of fistulas were transverse-sigmoid sinus in 6, middle fossa dura in 4, cavernous sinus in 2, and superior sagittal sinus in 1 patient. Cognard types were as follows : I in 4, IIa in 2, IIa+IIb in 5, and IV in 2. Embolization procedures were performed >=2 times in 3 patients. Nine patients were treated with transarterial Onyx embolization alone. One of these required direct surgical puncture of middle meningeal artery. Complete obliteration of fistulas was achieved in 11/13 (85%) patients. There were no complications except for 1 case of Onyx migration in cavernous dAVF. Modified Rankin scale score at post operative 3 months were 0 in 11, and 3 in 2 patients. CONCLUSION: Transarterial Onyx embolization can be a first line therapeutic option in patients with dAVFs. However, transvenous approach should be tried first in cavernous sinus dAVF because of the risk of intracranial migration of liquid embolic materials. Furthermore, combined surgical endovascular approach can be considered as a useful option in inaccessible route. PMID- 26885281 TI - Natural History of Unruptured Intracranial Aneurysms : A Retrospective Single Center Analysis. AB - OBJECTIVE: We conducted a retrospective cohort study to elucidate the natural course of unruptured intracranial aneurysms (UIAs) at a single institution. METHODS: Data from patients diagnosed with UIA from March 2000 to May 2008 at our hospital were subjected to a retrospective analysis. The cumulative and annual aneurysm rupture rates were calculated. Additionally, risk factors associated with aneurysmal rupture were identified. RESULTS: A total of 1339 aneurysms in 1006 patients met the inclusion criteria. During the follow-up period, 685 aneurysms were treated before rupture via either an open surgical or endovascular procedure. Six hundred fifty-four UIAs were identified and not repaired during the follow-up period. The mean UIA size was 4.5+/-3.2 mm, and 86.5% of the total UIAs had a largest dimension <7 mm. Among these UIAs, 18 ruptured at a median of 1.6 years (range : 27 days to 9.8 years) after day 0. The annual rupture risk during a 9-year follow-up was 1.00%. A multivariate Cox proportional hazards analysis revealed that the aneurysm size and a history of subarachnoid hemorrhage (SAH) were statistically significant risk factors for rupture. For an aneurysms smaller than 7 mm in the absence of a history of SAH, the annual rupture risk was 0.79%. CONCLUSION: In our study, the annual rupture risk for UIAs smaller than 7 mm in the absence of a history of SAH was higher than that of Western populations but similar to that of the Japanese population. PMID- 26885283 TI - Prognostic Role of Methylation Status of the MGMT Promoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients. AB - OBJECTIVE: This study investigated whether pyrosequencing can be used to determine the methylation status of the MGMT promoter as a clinical biomarker using relatively old archival tissue samples of glioblastoma. We also examined other prognostic factors for survival of glioblastoma patients. METHODS: The available study set included formalin-fixed paraffin-embedded (FFPE) tissue from 104 patients at two institutes from 1997 to 2012, all of which were diagnosed histopathologically as glioblastoma. Clinicopathologic data were collected by review of medical records. For pyrosequencing analysis, the PyroMark Q96 CpG MGMT kit (Qiagen, Hilden, Germany) was used to detect the level of methylation at exon 1 positions 17-39 of the MGMT gene, which contains 5 CpGs. RESULTS: Methylation of the MGMT promoter was detected in 43 (41.3%) of 104 samples. The average percentage methylation was 14.0+/-16.8% overall and 39.0+/-14.7% for methylated cases. There was no significant pattern of linear increase or decrease according to the age of the FFPE block (p=0.687). In multivariate analysis, age, performance status, extent of surgery, method of adjuvant therapy, and methylation status estimated by pyrosequencing were independently associated with overall survival. Additionally, patients with a high level of methylation survived longer than those with low methylation (p=0.016). CONCLUSION: In this study, the status and extent of methylation of the MGMT promoter analyzed by pyrosequencing were associated with overall survival in glioblastoma patients. Pyrosequencing is a quantitative method that overcomes the problems of MSP and a simple technique for accurate analysis of DNA sequences. PMID- 26885284 TI - Radiosurgery Compared with External Radiation Therapy as a Primary Treatment in Spine Metastasis from Hepatocellular Carcinoma : A Multicenter, Matched-Pair Study. AB - OBJECTIVE: The aim of this multicenter, matched-pair study was to compare the outcomes of stereotactic radiosurgery (SRS) and conventional external radiation therapy (RT) when used as a primary treatment in spine metastasis from hepatocellular carcinoma (HCC). METHODS: From 2005 to 2012, 28 patients underwent SRS as the primary treatment in spine metastasis from HCC. Based on sex, age, number of spine metastasis, Child-Pugh classification, interval from original tumor to spine metastasis, and year of treatment, 28 patients who underwent RT were paired. Outcomes of interest were pain relief, progression free survival, toxicities, and further treatment. RESULTS: The perioperative visual analog scale (VAS) decrease was larger in SRS group than in RT group, but the difference was not significant (3.7 vs. 2.8, p=0.13). When pain medication was adjusted, the number of patients with complete (n=6 vs.3) or partial (n=12 vs.13) relief was larger in SRS group than in RT group; however, the difference was not significant (p=0.83). There was no significant difference in progression free survival (p=0.48). In SRS group, 32.1% of patients had 1 or more toxicities whereas the percentage in RT group was 63.0%, a significant difference (p=0.04). Six SRS patients and 7 RT patients received further intervention at the treated segment. CONCLUSION: Clinical and radiological outcome were not significantly different between the two treatments. Toxicities, however, were more prevalent in the RT group. PMID- 26885285 TI - Malignant Glioma with Neuronal Marker Expression : A Clinicopathological Study of 18 Cases. AB - OBJECTIVE: Malignant gliomas with neuronal marker expression (MGwNM) are rare and poorly characterized. Increasingly diverse types of MGwNM have been described and these reported cases underscore the dilemmas in the classification and diagnosis of those tumors. The aim of this study is to provide additional insights into MGwNM and present the clinicopathological features of 18 patients. METHODS: We reviewed the medical records of 18 patients diagnosed as MGwNM at our institute between January 2006 and December 2012. Macroscopic total resection was performed in 11 patients (61%). We evaluated the methylation status of O(6)-methylguanine DNA methyltransferase (MGMT) and expression of isocitrate dehydrogenase 1 (IDH-1) in all cases, and deletions of 1p and 19q in available cases. RESULTS: The estimated median overall survival was 21.2 months. The median progression-free survival was 6.3 months. Six patients (33%) had MGMT methylation but IDH1 mutation was found in only one patient (6%). Gene analysis for 1p19q performed in nine patients revealed no deletion in six, 19q deletion only in two, and 1p deletion only in one. The extent of resection was significantly correlated with progression free survival on both univariate analysis and multivariate analysis (p=0.002 and p=0.013, respectively). CONCLUSION: In this study, the overall survival of MGwNM was not superior to glioblastoma. The extent of resection has a significant prognostic impact on progression-free survival. Further studies of the prognostic factors related to chemo-radio therapy, similar to studies with glioblastoma, are mandatory to improve survival. PMID- 26885286 TI - Evaluation of Non-Watertight Dural Reconstruction with Collagen Matrix Onlay Graft in Posterior Fossa Surgery. AB - OBJECTIVE: Many surgeons advocate for watertight dural reconstruction after posterior fossa surgery given the significant risk of cerebrospinal fluid (CSF) leak. Little evidence exists for posterior fossa dural reconstruction utilizing monolayer collagen matrix onlay graft in a non-watertight fashion. Our objective was to report the results of using collagen matrix in a non-watertight fashion for posterior fossa dural reconstruction. METHODS: We conducted a retrospective review of operations performed by the senior author from 2004-2011 identified collagen matrix (DuraGen) use in 84 posterior fossa operations. Wound complications such as CSF leak, infection, pseudomeningocele, and aseptic meningitis were noted. Fisher's exact test was performed to assess risk factor association with specific complications. RESULTS: Incisional CSF leak rate was 8.3% and non-incisional CSF leak rate was 3.6%. Incidence of aseptic meningitis was 7.1% and all cases resolved with steroids alone. Incidence of palpable and symptomatic pseudomeningocele in follow-up was 10.7% and 3.6% respectively. Postoperative infection rate was 4.8%. Previous surgery was associated with pseudomeningocele development (p<0.05). CONCLUSION: When primary dural closure after posterior fossa surgery is undesirable or not feasible, non-watertight dural reconstruction with collagen matrix resulted in incisional CSF leak in 8.3%. Incidence of pseudomeningocele, aseptic meningitis, and wound infection were within acceptable range. Data from this study may be used to compare alternative methods of dural reconstruction in posterior fossa surgery. PMID- 26885288 TI - Subarachnoid Hemorrhage Presenting with Seizure due to Cerebrospinal Fluid Leakage after Spinal Surgery. AB - Cerebrospinal fluid leakage may commonly occur during spinal surgeries and it may cause dural tears. These tears may result in hemorrhage in the entire compartments of the brain. Most common site of such hemorrhages are the veins in the cerebellar region. We report a case of hemorrhage, mimicking aneurysmal subarachnoid hemorrhage due to a cerebrospinal fluid leakage following lumbar spinal surgery and discuss the possible mechanisms of action. PMID- 26885287 TI - Sellar-Suprasellar Extraventricular Choroid Plexus Papilloma : A Case Report and Review of the Literature. AB - Choroid plexus papillomas (CPPs) are relatively rare neuroectodermal tumors that develop from choroid plexus epithelial cells and are usually restricted to the ventricles. Extraventricular CPPs are very unusual and can be difficult to diagnose and treat. A 50-year-old male patient was admitted to our clinic complaining of headache and visual deterioration. Neurological examination found no abnormalities except decreased light perception and secondary optic atrophy in the left eye. Endocrine testing revealed normal levels of hormones produced by the pituitary and target glands. Magnetic resonance imaging of the brain revealed a huge regular-shaped lesion in the sellar-suprasellar region occupying the sella turcica and extending into the suprasellar cistern and planum sphenoidale. The lesion was completely excised by microsurgery via an ordinary left-sided pterional approach. Histopathology identified the lesion as a choroid plexus papilloma. Following the case report, literature on the origin, differential diagnosis, and treatment of this rare tumor is reviewed. PMID- 26885289 TI - Cervical Spondylotic Myelopathy due to the Ochronotic Arthropathy of the Cervical Spine. AB - Ochronosis is a musculoskeletal manifestation of alkaptonuria, a rare hereditary metabolic disorder occurs due to the absence of homogentisic acid oxidase and leading to various systemic abnormalities related to deposition of homogentisic acid pigmentation (ochronotic pigmentation). The present case reports the clinical features, radiographic findings, treatments and results of a cervical spondylotic myelopathy woman patient due to the ochronotic arthropathy of the cervical spine. The patient aged 62 years was presented with gait disturbance and hand clumsiness. Physical examination, X-rays, computed tomography and lab results of the urine sample confirmed the presence of ochronosis with the involvement of the cervical spine. The patient underwent a modified cervical laminoplasty due to multi-segment spinal cord compression. The postoperative follow-up showed a good functional outcome with patient satisfaction. The present study concludes the conditions and important diagnostic and surgical aspects of a patient. It is necessary to identify the condition clinically and if cord compression is observed, appropriate surgical interventions needs to be instituted. PMID- 26885290 TI - Extended Pneumocephalus after Drainage of Chronic Subdural Hematoma Associated with Intracranial Hypotension : Case Report with Pathophysiologic Consideration. AB - Chronic subdural hematoma (SDH) is a well-known disease entity and is traditionally managed with surgery. However, when associated with spontaneous intracranial hypotension (SIH), the treatment strategy ought to be modified, as classical treatment could lead to unwanted consequences. A 59-year-old man presented with a case of SIH that manifested as a bilateral chronic SDH. He developed fatal extensive pneumocephalus and SDH re-accumulation as a complication of burr-hole drainage. Despite application of an epidural blood patch, the spinal cerebrospinal fluid leak continued, which required open spinal surgery. Chronic SDH management should not be overlooked, especially if the exact cause has not been determined. When chronic SDH assumed to be associated with SIH, the neurosurgeon should determine the exact cause of SIH in order to effectively correct the cause. PMID- 26885291 TI - Ultrasound Diagnosis of Double Crush Syndrome of the Ulnar Nerve by the Anconeus Epitrochlearis and a Ganglion. AB - Double compression of the ulnar nerve, including Guyon's canal syndrome associated with cubital tunnel syndrome caused by the anconeus epitrochlearis muscle, is a very rare condition. We present a case of double crush syndrome of the ulnar nerve at the wrist and elbow in a 55-year-old man, as well as a brief review of the literature. Although electrodiagnostic findings were consistent with an ulnar nerve lesion only at the elbow, ultrasonography revealed a ganglion compressing the ulnar nerve at the hypothenar area and the anconeus epitrochlearis muscle lying in the cubital tunnel. Careful physical examination and ultrasound assessment of the elbow and wrist confirmed the clinical diagnosis prior to surgery. PMID- 26885292 TI - A Case Report of the Angiosarcoma Involving Epicranial Muscle and Fascia : Is the Occipitofrontalis Muscle Composed of Two Different Muscles? AB - The occipitofrontalis muscle is generally regarded as one muscle composed of two muscle bellies joined through the galea aponeurotica. However, two muscle bellies have different embryological origin, anatomical function and innervations. We report a case of angiosarcoma of the scalp in a 63-year-old man whose MR showed that the superficial fascia overlying the occipital belly becomes the temporoparietal fascia and ends at the superior end of the frontal belly. Beneath the superficial fascia, the occipital belly of the occipitofrontalis muscle becomes the galea aponeurotica and inserts into the underside of the frontal belly. The presented case report supported the concept of which the occipitofrontalis muscle appears to be composed of two anatomically different muscles. PMID- 26885293 TI - Is postoperative nausea and vomiting still the big "little" problem? PMID- 26885294 TI - Perioperative lung-protective ventilation strategy reduces postoperative pulmonary complications in patients undergoing thoracic and major abdominal surgery. AB - The occurrence of postoperative pulmonary complications is strongly associated with increased hospital mortality and prolonged postoperative hospital stays. Although protective lung ventilation is commonly used in the intensive care unit, low tidal volume ventilation in the operating room is not a routine strategy. Low tidal volume ventilation, moderate positive end-expiratory pressure, and repeated recruitment maneuvers, particularly for high-risk patients undergoing major abdominal surgery, can reduce postoperative pulmonary complications. Facilitating perioperative bundle care by combining prophylactic and postoperative positive pressure ventilation with intraoperative lung-protective ventilation may be helpful to reduce postoperative pulmonary complications. PMID- 26885295 TI - Nonparametric statistical tests for the continuous data: the basic concept and the practical use. AB - Conventional statistical tests are usually called parametric tests. Parametric tests are used more frequently than nonparametric tests in many medical articles, because most of the medical researchers are familiar with and the statistical software packages strongly support parametric tests. Parametric tests require important assumption; assumption of normality which means that distribution of sample means is normally distributed. However, parametric test can be misleading when this assumption is not satisfied. In this circumstance, nonparametric tests are the alternative methods available, because they do not required the normality assumption. Nonparametric tests are the statistical methods based on signs and ranks. In this article, we will discuss about the basic concepts and practical use of nonparametric tests for the guide to the proper use. PMID- 26885296 TI - The effect of electromagnetic guidance system on early learning curve of ultrasound for novices. AB - BACKGROUND: Electromagnetic guidance reveals needle alignment and position relative to the image plane on an ultrasound view. This study compared the early learning curves of novices performing ultrasound-guided needle placement with (n = 10) or without electromagnetic guidance (n = 10). METHODS: Participants performed 30 ultrasound-guided needle placements using an echogenic stick (0.3-cm diameter) as a target inside a phantom model; this early learning period was divided into sequential periods (P1: 1-5, P2: 6-10, P3: 11-15, P4: 16-20, P5: 21 25, P6: 26-30 attempts). RESULTS: Using an in-plane approach, the time required for needle placement in the EMG group was significantly shorter than that of the non-EMG group in P1, P2, P4, and P6 and the number of needle advances of the EMG group was significantly smaller than that of the non-EMG group in P1 and P2. Using an out-of-plane approaches, the time required for needle placement in the EMG group was significantly shorter than that of the non-EMG group in all periods, but the number of needle advances was similar between both groups in P1 P5. CONCLUSIONS: The electromagnetic guidance system may be beneficial when performing ultrasound guided peripheral nerve blocks or vascular cannulation in the early learning period, especially by inexperienced operators with reducing patient risk. PMID- 26885297 TI - Comparison of clinical validation of acceleromyography and electromyography in children who were administered rocuronium during general anesthesia: a prospective double-blinded randomized study. AB - BACKGROUND: Electromyography and acceleromyography are common neuromuscular monitoring devices. However, questions still remain regarding the use of acceleromyography in children. This study compared the calibration success rates and intubation conditions in children after obtaining the maximal blockade depending on each of the devices. METHODS: Children, 3 to 6 years old, were randomly allocated to the TOF-Watch SX acceleromyography group or the NMT electromyography group. The induction was performed with propofol, fentanyl, and rocuronium. The bispectral index and 1 Hz single twitch were monitored during observation. The calibration of the each device was begun when the BIS dropped to 60. After successful calibration, rocuronium 0.6 mg/kg was injected. A tracheal intubation was performed when the twitch height suppressed to 0. The rocuronium onset time (time from administration to the maximal depression of twitch height) and intubating conditions were rated in a blinded manner. RESULTS: There was no difference in the calibration success rates between the two groups; and the calibration time in the electromyography group (16.7 +/- 11.0 seconds) was shorter than the acceleromyography group (28.1 +/- 13.4 seconds, P = 0.012). The rocuronium onset time of the electromyography group (73.6 +/- 18.9 seconds) was longer than the acceleromyography group (63.9 +/- 18.8 seconds, P = 0.042) and the intubation condition of the electromyography group (2.27 +/- 0.65) was better than the acceleromyography group (1.86 +/- 0.50, P = 0.007). CONCLUSIONS: Electromyography offers a better compromise than acceleromyography with respect to the duration of calibration process and surrogate for the optimal time of tracheal intubation in children. PMID- 26885298 TI - The effect of Valsalva maneuver in attenuating skin puncture pain during spinal anesthesia: a randomized controlled trial. AB - BACKGROUND: Valsalva maneuver reduces pain by activating sinoaortic baroreceptor reflex arc. We planned this study to evaluate the role of valsalva in attenuating spinal needle-puncture pain. METHODS: Ninety American Society of Anesthesiologists (ASA) grade I and II enrolled patients undergoing elective surgery were randomized into 3 groups of 30 each. Group I (Control): didn't blow; group II (Distraction): patients blew into rubber tube; Group III (Valsalva): blew into sphygmomanometer tube and raise mercury column up to 30 mmHg for at least 20 seconds. During above procedures, spinal puncture was performed with 25 gauge spinal needle. RESULTS: Eighty-two patient data were analyzed. Incidence of spinal puncture pain was reduced to 10% (3 of 27) in Valsalva group as compared to 100% (28 of 28 in control group and 27 of 27 in Distraction group) observed in other two groups (P < 0.05). Severity of lumbar puncture pain as assessed by visual analog scale (0-10; where 0 is no pain and 10 is the worst imaginable pain) presented as Median (Interquartile range) were significantly reduced in the Valsalva group (0.0 [0.0] as compared to other 2 groups 2.0 [0.0] in the Distraction group and 3.0 [0.8] in Control group) (P < 0.05). Regarding time taken by CSF to fill spinal needle hub, there was no difference among the three groups (P > 0.05). None patient of all groups had post dural puncture headache (P > 0.05). CONCLUSIONS: Valsalva can be performed routinely in ASA I and II patients undergoing spinal anesthesia as it is safe, painless and non pharmacological method of pain attenuation. PMID- 26885299 TI - Can bedside patient-reported numbness predict postoperative ambulation ability for total knee arthroplasty patients with nerve block catheters? AB - BACKGROUND: Adductor canal catheters offer advantages over femoral nerve catheters for knee replacement patients because they produce less quadriceps muscle weakness; however, applying adductor canal catheters in bedside clinical practice remains challenging. There is currently no patient-reported outcome that accurately predicts patients' physical function after knee replacement. The present study evaluates the validity of a relatively new patient-reported outcome, i.e., a numbness score obtained using a numeric rating scale, and assesses its predictive value on postoperative ambulation. METHODS: We conducted a retrospective cohort study pooling data from two previously-published clinical trials using identical research methodologies. Both studies recruited patients undergoing knee replacement; one studied adductor canal catheters while the other studied femoral nerve catheters. Our primary outcome was patient-reported numbness scores on postoperative day 1. We also examined postoperative day 1 ambulation distance and its association with postoperative numbness using linear regression, adjusting for age, body mass index, and physical status. RESULTS: Data from 94 subjects were included (femoral subjects, n = 46; adductor canal subjects, n = 48). Adductor canal patients reported decreased numbness (median [10(th)-90(th) percentiles]) compared to femoral patients (0 [0-5] vs. 4 [0-10], P = 0.001). Adductor canal patients also ambulated seven times further on postoperative day 1 relative to femoral patients. There was a significant association between postoperative day 1 total ambulation distance and numbness (Beta = -2.6; 95% CI: -4.5, -0.8, P = 0.01) with R(2) = 0.1. CONCLUSIONS: Adductor canal catheters facilitate improved early ambulation and produce less patient-reported numbness after knee replacement, but the correlation between these two variables is weak. PMID- 26885300 TI - Arrhythmogenic potential develops rapidly at graft reperfusion before the start of hypotension during living-donor liver transplantation. AB - BACKGROUND: Detailed profiles of acute hypothermia and electrocardiographic (ECG) manifestations of arrhythmogenicity were examined to analyze acute hypothermia and ventricular arrhythmogenic potential immediately after portal vein unclamping (PVU) in living-donor liver transplantation (LT). METHODS: We retrospectively analyzed electronically archived medical records (n = 148) of beat-to-beat ECG, arterial pressure waveforms, and blood temperature (BT) from Swan-Ganz catheters in patients undergoing living-donor LT. The ECG data analyzed were selected from the start of BT drop to the initiation of systolic hypotension after PVU. RESULTS: On reperfusion, acute hypothermia of < 34C, < 33C and < 32C developed in 75.0%, 37.2% and 11.5% of patients, respectively. BT decreased from 35.0C +/- 0.8C to 33.3C +/- 1.0C (range 35.8C-30.5C). The median time to nadir of BT was 10 s after PVU. Difference in BT (DeltaBT) was weakly correlated with graft recipient weight ratio (GRWR; r = 0.22, P = 0.008). Compared to baseline, arrhythmogenicity indices such as corrected QT (QTc), Tp-e (T wave peak to end) interval, and Tp-e/QTc ratio were prolonged (P < 0.001 each). ST height decreased and T amplitude increased (P < 0.001 each). However, no correlation was found between DeltaBT and arrhythmogenic indices. CONCLUSIONS: In living-donor LT, regardless of extent of BT drop, ventricular arrhythmogenic potential developed immediately after PVU prior to occurrence of systolic hypotension. PMID- 26885301 TI - Changes in cerebral oxygen saturation and early postoperative cognitive function after laparoscopic gastrectomy: a comparison with conventional open surgery. AB - BACKGROUND: Laparoscopic gastrectomy requires a reverse-Trendelenburg position and prolonged pneumoperitoneum and it could cause significant changes in cerebral homeostasis and lead to cognitive dysfunction. We compared changes in regional cerebral oxygen saturation (rSO2), early postoperative cognitive function and hemodynamic variables in patients undergoing laparoscopic gastrectomy with those patients that underwent conventional open gastrectomy. METHODS: Sixty patients were enrolled in this study and the patients were distributed to receive either laparoscopic gastrectomy (laparoscopy group, n = 30) or open conventional gastrectomy (open group, n = 30). rSO2, end-tidal carbon dioxide tension, hemodynamic variables and arterial blood gas analysis were monitored during the operation. The enrolled patients underwent the mini-mental state examination 1 day before and 5 days after surgery for evaluation of early postoperative cognitive function. RESULTS: Compared to baseline value, rSO2 and end-tidal carbon dioxide tension increased significantly in the laparoscopy group after pneumoperitoneum, whereas no change was observed in the open group. No patient experienced cerebral oxygen desaturation or postoperative cognitive dysfunction. Changes in mean arterial pressure over time were significantly different between the groups (P < 0.001). CONCLUSIONS: Both laparoscopic and open gastrectomy did not induce cerebral desaturation or early postoperative cognitive dysfunction in patients under desflurane anesthesia. However, rSO2 values during surgery favoured laparoscopic surgery, which was possibly related to increased cerebral blood flow due to increased carbon dioxide tension and the effect of a reverse Trendelenburg position. PMID- 26885302 TI - Effects of intraoperative single bolus fentanyl administration and remifentanil infusion on postoperative nausea and vomiting. AB - BACKGROUND: Although the use of postoperative opioids is a well-known risk factor for postoperative nausea and vomiting (PONV), few studies have been performed on the effects of intraoperative opioids on PONV. We examined the effects of a single bolus administration of fentanyl during anesthesia induction and the intraoperative infusion of remifentanil on PONV. METHODS: Two hundred and fifty women, aged 20 to 65 years and scheduled for thyroidectomy, were allocated to a control group (Group C), a single bolus administration of fentanyl 2 ug/kg during anesthesia induction (Group F), or 2 ng/ ml of effect-site concentration controlled intraoperative infusion of remifentanil (Group R) groups. Anesthesia was maintained with sevoflurane and 50% N2O. The incidence and severity of PONV and use of rescue antiemetics were recorded at 2, 6, and 24 h postoperatively. RESULTS: Group F showed higher incidences of nausea (60/82, 73% vs. 38/77, 49%; P = 0.008), vomiting (40/82, 49% vs. 23/77 30%; P = 0.041) and the use of rescue antiemetics (47/82, 57% vs. 29/77, 38%; P = 0.044) compared with Group C at postoperative 24 h. However, there were no significant differences in the incidence of PONV between Groups C and R. The overall incidences of PONV for postoperative 24 h were 49%, 73%, and 59% in Groups C, F, and R, respectively (P = 0.008). CONCLUSIONS: A single bolus administration of fentanyl 2 ug/kg during anesthesia induction increases the incidence of PONV, but intraoperative remifentanil infusion with 2 ng/ml effect-site concentration did not affect the incidence of PONV. PMID- 26885304 TI - Vagally mediated atrioventricular block with ventricular asystole immediately after assuming prone position under spinal anestheisa: a case report. AB - Vagally mediated atrioventricular (AV) block is a condition which a paroxysmal AV block occurs with the slowing of the sinus rate. Owing to its unpredictability and benign nature, it often goes unrecognized in clinical practice. We present the case of a 49-year-old man who suddenly lost consciousness when he assumed a prone position for hemorrohoidectomy under spinal anesthesia; continuous electrocardiographic recording revealed AV block with ventricular asystole. He was completely recovered after returning to a supine position. This case calls our attention to fatal manifestation of vagally mediated AV block leading to syncope. PMID- 26885305 TI - Paraplegia following cervical epidural catheterization using loss of resistance technique with air: a case report. AB - We report a case of paraplegia without neurologic deficit of upper extremities following cervical epidural catheterization using air during the loss of resistance technique. A 41-year-old woman diagnosed with complex regional pain syndrome had upper and lower extremity pain. A thoracic epidural lead was inserted for a trial spinal cord stimulation for treating lower extremity pain and cervical epidural catheterization was performed for treating upper extremity pain. Rapidly progressive paraplegia developed six hours after cervical epidural catheterization. Spine CT revealed air entrapment in multiple thoracic intervertebral foraminal spaces and surrounding epidural space without obvious spinal cord compression before the decompressive operation, which disappeared one day after the decompressive operation. Her paraplegia symptoms were normalized immediately after the operation. The presumed cause of paraplegia was transient interruption of blood supply to the spinal cord through the segmental radiculomedullary arteries feeding the spinal cord at the thoracic level of the intervertebral foramen caused by the air. PMID- 26885303 TI - Lipofundin(r) MCT/LCT 20% increase left ventricular systolic pressure in an ex vivo rat heart model via increase of intracellular calcium level. AB - BACKGROUND: Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. METHODS: We measured hemodynamic effects using a digital analysis system after Intralipid(r) and Lipofundin(r) MCT/LCT were infused into hearts hanging in a Langendorff perfusion system. We measured the effects of the lipid emulsions on intracellular calcium levels in H9c2 cells by confocal microscopy. RESULTS: Infusion of Lipofundin(r) MCT/LCT 20% (1 ml/kg) resulted in a significant increase in left ventricular systolic pressure compared to that after infusing modified Krebs-Henseleit solution (1 ml/kg) (P = 0.003, 95% confidence interval [CI], 2.4-12.5). Lipofundin(r) MCT/LCT 20% had a more positive inotropic effect than that of Intralipid(r) 20% (P = 0.009, 95% CI, 1.4 11.6). Both lipid emulsion treatments increased intracellular calcium levels. Lipofundin(r) MCT/LCT (0.01%) increased intracellular calcium level more than that of 0.01% Intralipid(r) (P < 0.05, 95% CI, 0.0-1.9). CONCLUSIONS: These two lipid emulsions had different inotropic effects depending on their triglyceride component. The inotropic effect of lipid emulsions could be related with intracellular calcium level. PMID- 26885306 TI - Usefulness of intraoperative bronchoscopy during surgical repair of a congenital cardiac anomaly with possible airway obstruction: three cases report. AB - Compression of the airway is relatively common in pediatric patients, although it is often an unrecognized complication of congenital cardiac and aortic arch anomalies. Aortopexy has been established as a surgical treatment for tracheobronchial obstruction associated with vascular anomaly, aortic arch anomaly, esophageal atresia, and tracheoesophageal fistula. The tissue-to-tissue arch repair technique could result in severe airway complication such as compression of the left main bronchus which was not a problem before the correction. We report three cases of corrective open heart surgery monitored by intraoperative bronchoscopy performed during prebypass, and performed immediately before weaning from bypass, to evaluate tracheobronchial obstruction caused by congenital, complex cardiac anomalies in the operating room. PMID- 26885307 TI - Stanford type A aortic dissection in a patient with Marfan syndrome during pregnancy: a case report. AB - Aortic dissection during pregnancy is a devastating event for both the pregnant woman and the baby. We report a case of acute aortic dissection (Stanford type A) in a pregnant woman with Marfan syndrome at the 29(th) week of gestation. She underwent a cesarean section followed by an ascending aorta and total arch replacement with cardiopulmonary bypass, without a prior sternotomy. The hemodynamic parameters were kept stable during the cesarean section by using inotropes and vasopressors under transesophageal echocardiography monitoring. The newborn survived after endotracheal intubation and management in a neonatal intensive care unit. PMID- 26885308 TI - Cerebral air embolism and subsequent transient neurologic abnormalities in a liver transplant recipient following the removal of the pulmonary artery catheter from the central venous access device: a case report. AB - Cerebral air embolism is a rare but potentially life-threatening complication. We experienced a living-donor liver transplant recipient who presented with unexpected cerebral air embolism and transient neurologic abnormalities that subsequently developed just after the removal of the pulmonary artery catheter from the central venous access device. One day after the initial event, the patient's neurologic status gradually improved. The patient was discharged 30 days after liver transplantation without neurologic sequelae. PMID- 26885309 TI - Effectiveness of applying continuous positive airway pressure in a patient with paradoxical vocal fold movement after endotracheal extubation: a case report. AB - Paradoxical vocal fold movement (PVFM) is an uncommon upper airway disorder defined as paradoxical adduction of the vocal folds during inspiration. The etiology and treatment of PVFM are unclear. The physician should manage this condition because of the possibility of near complete airway obstruction in severe case of PVFM. We report a case of successful airway management in a patient with PVFM by applying continuous positive airway pressure (CPAP). In this case, PVFM was detected after removing an endotracheal tube from a 67-year-old male who underwent excision of a laryngeal mass. The patient recovered without complications in 1 day with support by CPAP. PMID- 26885310 TI - Carbon dioxide pneumothorax occurring during laparoscopy-assisted gastrectomy due to a congenital diaphragmatic defect: a case report. AB - During laparoscopic surgery, carbon dioxide (CO2) pneumothorax can develop due to a congenital defect in the diaphragm. We present a case of a spontaneous massive left-sided pneumothorax that occurred during laparoscopy-assisted gastrectomy, because of an escape of intraperitoneal CO2 gas, under pressure, into the pleural cavity through a congenital defect in the esophageal hiatus of the left diaphragm. This was confirmed on intraoperative chest radiography and laparoscopic inspection. This CO2 pneumothorax caused tolerable hemodynamic and respiratory consequences, and was rapidly reversible after release of the pneumoperitoneum. Thus, a conservative approach was adopted, and the remainder of the surgery was completed, laparoscopically. Due to the high solubility of CO2 gas and the extra-pulmonary mechanism, CO2 pneumothorax with otherwise hemodynamically stable conditions can be managed by conservative modalities, avoiding unnecessary chest tube insertion or conversion to an open procedure. PMID- 26885311 TI - Arytenoid dislocation after uneventful endotracheal intubation: a case report. AB - Arytenoid dislocation is an unusual complication of endotracheal intubation. We reported a case of a 48-year-old female with arytenoid dislocation after uneventful endotracheal intubation, which was successfully treated with arytenoid reduction. The patient complained of persistent hoarseness until the fourth day after an uneventful gynecologic surgery under general anesthesia. On laryngoscopic examination, paralyzed left vocal cord with minimal arytenoid movement was observed. An anteromedial dislocation of the left arytenoid cartilage was suspected and surgical reduction was performed by the laryngologist. The hoarseness was immediately resolved after surgical intervention. Anesthesiologists should be careful not to cause laryngeal trauma in anesthetized patients. In addition, early diagnosis and prompt surgical reduction are essential for a better prognosis for arytenoid dislocation. PMID- 26885313 TI - Erratum: A comparison of postoperative emergence agitation between sevoflurane and thiopental anesthesia induction in pediatric patients (Korean J Anesthesiol 2015 Aug; 68(4): 373-378). AB - [This corrects the article on p. 373 in vol. 68, PMID: 26257850.]. PMID- 26885312 TI - Statistical review of 95 studies employing repeated-measures analysis of variance published in the Korean Journal of Anesthesiology. PMID- 26885314 TI - Authorship. PMID- 26885315 TI - Drinking Amount Associated with Abnormal Gamma-Glutamyl Transpeptidase Expression in Women. AB - BACKGROUND: This study investigated whether there is any difference in drinking amount associated with abnormal expression of gamma-glutamyl transpeptidase (GGT), one of the biological markers of excessive drinking, between flushing and non-flushing women after drinking. METHODS: The subjects were 797 women aged 20 59 years old who visited health promotion center of Chungnam National University Hospital between January, 2013 and July, 2014. Facial flushing status after drinking, amount of alcohol consumed per drinking episode, and the number of drinking days per week were assessed using a questionnaire. Age, abnormal GGT expression, smoking status, menopauase status, and body mass index (BMI) were obtained from the health screening data. The weekly drinking amount were categorized into <4 drinks; >=4, <8 drinks; and >=8 drinks. The association of abnormal GGT expression with weekly drinking amount was analyzed using multivariate logistic regression after controlling for confounding variables including age, smoking status, menopauase status, and BMI. RESULTS: Compared to nondrinkers, the abnormal GGT expression in the non-flushing group was significantly increased when the weekly drinking amount was >=4 drinks (>=4, <8 drinks: adjusted odds ratio [aOR], 37.568; 95% confidence interval [CI], 9.793 144.116; >=8 drinks: aOR, 20.350; 95% CI, 20.350-305.138). On the other hand, the abnormal GGT expression in the flushing group was significantly increased in every weekly drinking amount range (<4 drinks: aOR, 4.120; 95% CI, 1.603-10.585; >=4, <8 drinks: aOR, 79.206; 95% CI, 24.034-261.031; >=8 drinks: aOR, 111.342; 95% CI, 30.987-400.079). For each weekly drinking amount range, the flushing group showed significantly higher abnormal GGT expression than the non-flushing group (<4 drinks: aOR, 3.867; 95% CI, 1.786-8.374; >=4, <8 drinks: aOR, 57.277; 95% CI, 24.430-134.285; >=8 drinks: aOR, 104.871; 95% CI, 42.945-256.091). CONCLUSION: This study showed that abnormal GGT expression in the flushing female drinkers was induced by smaller amounts of alcohol than in the non-flushing female drinkers. PMID- 26885316 TI - Effect of Coffee Consumption on the Progression of Type 2 Diabetes Mellitus among Prediabetic Individuals. AB - BACKGROUND: A previous large-scale cohort study investigated the relationship between coffee intake and the progression of diabetes mellitus in the United States. However, studies on the effects of coffee on diabetes are rare in South Korea. Therefore, this study assessed the amount and method of coffee intake in Koreans in order to determine if coffee intake has a prophylactic effect on diabetes progression. METHODS: This study included 3,497 prediabetic patients from a single medical institution, with glycated hemoglobin levels ranging from 5.7% to 6.4%. Cross-tabulation and Kaplan-Meier survival analyses were performed to compare patients with and without diabetes progression based on the frequency and method of coffee intake. Cox proportional hazard analysis was performed to correct for confounding variables. RESULTS: The observation period (mean+/ standard deviation) was 3.7+/-2.3 years. Kaplan-Meier survival analysis revealed that the risk of diabetes progression was lowest in patients who drank black coffee three or more times per day (P=0.036). However, correction for confounding variables in Cox proportional hazard analysis revealed that, while the risk was lower for the patients who typically consumed black coffee than for those who mixed creamer and sugar into their coffees, the difference was not significant. CONCLUSION: The results of this study suggest that drinking coffee without sugar and creamer at least three times daily has the greatest preventive effect on diabetes onset. PMID- 26885317 TI - Development of a Modified Korean East Asian Student Stress Inventory by Comparing Stress Levels in Medical Students with Those in Non-Medical Students. AB - BACKGROUND: Medical students are usually under more stress than that experienced by non-medical students. Stress testing tools for Korean medical students have not been sufficiently studied. Thus, we adapted and modified the East Asian Student Stress Inventory (EASSI), a stress testing tool for Korean students studying abroad, and verified its usefulness as a stress test in Korean university students. We also compared and analyzed stress levels between medical and non-medical students. METHODS: A questionnaire survey was conducted on medical and non-medical students of a national university, and the responses of 224 students were analyzed for this study. Factor analysis and reliability testing were performed based on data collected for 25 adapted EASSI questions and those on the Korean version of the Global Assessment of Recent Stress Scale (GARSS). A correlation analysis was performed between the 13 modified EASSI questions and the GARSS, and validity of the modified EASSI was verified by directly comparing stress levels between the two student groups. RESULTS: The 13 questions adapted for the EASSI were called the modified EASSI and classified into four factors through a factor analysis and reliability testing. The Pearson's correlation analysis revealed a significant correlation between the modified EASSI and the Korean version of the GARSS, suggesting a complementary strategy of using both tests. CONCLUSION: The validity and reliability of the EASSI were verified. The modified Korean EASSI could be a useful stress test for Korean medical students. Our results show that medical students were under more stress than that of non-medical students. Thus, these results could be helpful for managing stress in medical students. PMID- 26885318 TI - Development of a Simple Tool for Identifying Alcohol Use Disorder in Female Korean Drinkers from Previous Questionnaires. AB - BACKGROUND: This study aimed to develop a simple tool for identifying alcohol use disorders in female Korean drinkers from previous questionnaires. METHODS: This research was conducted on 400 women who consumed at least one alcoholic drink during the past month and visited the health promotion center at Chungnam National University Hospital between June 2013 to May 2014. Drinking habits and alcohol use disorders were assessed by structured interviews using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnostic criteria. The subjects were also asked to answer the Alcohol Use Disorders Identification Test (AUDIT), AUDIT-Consumption, CAGE (Cut down, Annoyed, Guilty, Eye-opener), TWEAK (Tolerance, Worried, Eye-opener, Amnesia, Kut down), TACE (Tolerance, Annoyed, Cut down, Eye-opener), and NET (Normal drinker, Eye-opener, Tolerance) questionnaires. The area under receiver operating characteristic (AUROC) of each question of the questionnaires on alcohol use disorders was assessed. After combining two questions with the largest AUROC, it was compared to other previous questionnaires. RESULTS: Among the 400 subjects, 58 (14.5%) were identified as having an alcohol use disorder. Two questions with the largest AUROC were question no. 7 in AUDIT, "How often during the last year have you had a feeling of guilt or remorse after drinking?" and question no. 5 in AUDIT, "How often during the past year have you failed to do what was normally expected from you because of drinking?" with an AUROC (95% confidence interval [CI]) of 0.886 (0.850-0.915) and 0.862 (0.824-0.894), respectively. The AUROC (95% CI) of the combination of the two questions was 0.958 (0.934-0.976) with no significant difference as compared to the existing AUDIT with the largest AUROC. CONCLUSION: The above results suggest that the simple tool consisting of questions no. 5 and no. 7 in AUDIT is useful in identifying alcohol use disorders in Korean female drinkers. PMID- 26885319 TI - Correlation between Overactive Bladder Syndrome and Obsessive Compulsive Disorder in Women. AB - BACKGROUND: Overactive bladder syndrome is characterized by urinary urgency, usually accompanied by Frequent urination and nocturia, with or without urgent urinary incontinence. There must be the absence of causative infection or pathological conditions. Overactive bladder syndrome is related to mental disorders, particularly depression and anxiety. However, obsessive-compulsive symptoms are investigated much less frequently. The purpose of the present study was thus to assess obsessive-compulsive symptoms in overactive bladder syndrome patients. METHODS: Fifty-seven women patients with overactive bladder syndrome and fifty-seven women without it (age matched control group) were prospectively enrolled. They completed the overactive bladder syndrome-validated 8-question screener and the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire at the same time they visited the clinic. Patients were compared with controls on the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire and its checking, tidiness, doubting, and fear of contamination components. RESULTS: Patients showed more obsessive traits than controls on the Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire total score (P=0.006) and on the checking subscale (P=0.001). Odds ratio for the overactive bladder syndrome group's obsessive-compulsive symptoms traits (score>=14) was 5.47 (P=0.001). The Korean version of the Maudsley Obsessional-Compulsive Inventory Questionnaire total score was associated with the overactive bladder syndrome-validated 8-question screener score in patients (P=0.03). CONCLUSION: Obsessive-compulsive symptoms may constitute an important aspect of the psychiatric profile of overactive bladder syndrome patients. The severity of obsessive-compulsive symptoms seems to be related to the degree of the overactive bladder syndrome severity. Clinicians may consider screening women with overactive bladder syndrome for obsessive-compulsive symptoms. PMID- 26885321 TI - Sarcopenia Is Not Associated with Depression in Korean Adults: Results from the 2010-2011 Korean National Health and Nutrition Examination Survey. AB - BACKGROUND: Sarcopenia is associated with metabolic disorders, cardiovascular disease, and mortality; however, its association with depression in the general population remains unknown. Therefore, we investigated this association in Korea. METHODS: This study included 8,958 and 8,518 subjects from the 2010-2011 Korean National Health and Nutrition Examination Survey V-1, 2. The study was restricted to participants >=20 years of age who had completed the survey, including whole body dual-energy X-ray absorptiometry scans. After exclusion, 7,364 subjects were included in our final analysis. Age was categorized into three groups (20-39, 40 59, and >=60 years), and subjects were categorized according to their sarcopenic and obesity status. Depression was categorized into three groups (not depressed, depressed, and depression). RESULTS: The sarcopenia group did not have a higher prevalence of depression or depressive symptoms compared to the nonsarcopenia group; the same was true even when obesity was considered. All age groups showed non-significant associations between sarcopenia and depression. In multivariate logistic regression models, no significant associations were observed between sarcopenia and prevalence of depression or depressed symptoms in men and women. CONCLUSION: We found no associations between sarcopenia and the prevalence of depression or depressed symptoms in Korean adults. Future large prospective studies and randomized controlled trials are needed to further assess this relationship. PMID- 26885320 TI - Association between Metabolic Syndrome and Menstrual Irregularity in Middle-Aged Korean Women. AB - BACKGROUND: Menstrual irregularity is a common major complaint in women of reproductive age. It is also a known marker for underlying insulin resistance. We investigated the association between menstrual irregularity and metabolic syndrome in the general population of middle-aged women in Korea. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey 2010-2012. A total of 2,742 subjects were included in the analysis. Participants were divided into two categories based on their menstrual cycle regularity and the relationship between metabolic syndrome and its variables was investigated by multiple logistic regression analysis. RESULTS: Adjusted analyses revealed significantly higher odds ratios for metabolic syndrome, high waist circumference, high triglyceride levels, and low high density lipoprotein cholesterol levels with the presence of menstrual irregularity. CONCLUSION: Metabolic syndrome and its components (high waist circumference, high triglyceride levels, and low high density lipoprotein cholesterol levels) were significantly associated with menstrual irregularity in women of reproductive age. PMID- 26885322 TI - Relationship between Metabolic Syndrome and Rheumatoid Arthritis. AB - BACKGROUND: Rheumatoid arthritis (RA) and metabolic syndrome (Mets) are considered to be diseases with common traits that can increase the risk of cardiovascular disease incidence; studies in other countries examined the relationship between these diseases. However, existing studies did not show consistent results. In the present study, the relationship between RA and Mets in Koreans was examined using the data of the 4th and 5th Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: The present study used the data of the 4th and 5th KNHANES, conducted between 2007 and 2012. Among 25,812 adults aged over 40, 19,893 were selected as study subjects, excluding 5,919 who did not have variable information needed for the analysis. T-test and chi-square test were used for the analysis of related variables. To determine the relationship between diagnostic status of RA and Mets, multivariate logistic regression analysis was performed by controlling confounding variables, which were selected through literature review and statistical analysis. RESULTS: Multivariate logistic regression analysis was conducted to examine the relationship between diagnostic status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, the prevalence of Mets was lower in RA patients (adjusted odds ratio [aOR], 0.79; 95% confidence interval [CI], 0.65 to 0.96). Multivariate logistic regression analysis was performed to examine the relationship between treatment status of RA and Mets. When age, education level, average monthly household income, smoking, alcohol consumption, and level of physical activity were adjusted, there was a significant negative correlation in women (aOR, 0.65; 95% CI, 0.44 to 0.96). CONCLUSION: The relationship between RA and Mets showed a significantly negative correlation in Korean women. The group that received RA treatment showed significantly lower prevalence of the Mets as compared to the untreated group in Korean RA women. PMID- 26885323 TI - Association between Sleep Duration and Impaired Fasting Glucose in Korean Adults: Results from the Korean National Health and Nutrition Examination Survey 2011 2012. AB - BACKGROUND: Impaired fasting glucose (IFG) is an established risk factor for type 2 diabetes and cardiovascular disease. This study evaluated the relationship between sleep duration and IFG. METHODS: This cross-sectional study included 14,925 Korean adults (5,868 men and 9,057 women) >=19 years of age who participated in the Korean National Health and Nutrition Examination Survey between 2011 and 2012. Blood glucose levels were measured after at least eight hours of fasting. Study subjects were categorized into three groups based on self reported sleep duration (<7, 7-8, or >8 h/d). IFG was diagnosed according to recommendations American Diabetes Association guidelines. Multiple logistic regression analysis was performed with adjustment for covariates. RESULTS: In men, short sleep duration (<7 hours) was associated with increased risk of IFG (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08 to 1.96) compared to adequate sleep duration (7-8 hours), whereas long sleep duration (>8 hours) was not associated with risk of IFG (OR, 0.90; 95% CI, 0.37 to 2.18). In women, sleep duration was not associated with risk of IFG. CONCLUSION: The association between sleep duration and IFG differed by sex; sleep deprivation, was associated with increased risk of IFG, especially in men. PMID- 26885324 TI - Association between Body Mass Index, Waist Circumference and Prevalence of Microalbuminuria in Korean Adults of Age 30 Years and Older without Diabetes, Hypertension, Renal Failure, or Overt Proteinuria: The 2013 Korean National Health and Nutrition Examination Survey. AB - BACKGROUND: Microalbuminuria and obesity markers are known risk factors for cardiovascular or renal disease. This study aimed to evaluate the prevalence of microalbuminuria according to body mass index (BMI) and abdominal obesity criteria. METHODS: The study subjects included 3,979 individuals aged 30 years or older who did not have diabetes, hypertension, renal failure, or overt proteinuria, from among those who participated in The Korean National Health and Nutrition Examination Survey in 2013, a cross-sectional, nationally representative, stratified survey. Microalbuminuria was defined as a urinary albumin to creatinine ratio of 30 to 300 mg/g. BMI and waist circumference were classified according to the Asia-Pacific criteria. RESULTS: The prevalence of microalbuminuria was found to be 5.1%. In the normoalbuminuria group, 3.4%, 41.7%, 24%, 27.6%, and 3.2% of participants were included in the underweight, normal, overweight, obesity 1, and obesity 2 groups, respectively. These percentages in the microalbuminuria group were 7.1%, 34.5%, 19.2%, 28.6%, and 10.6%, respectively (P<0.001). The waist circumference in men was 21.4% in the normoalbuminuria group and 36.5% in the microalbuminuria group (P=0.004). Logistic regression analyses were performed to evaluate the relationship between the presence of microalbuminuria and BMI or waist circumference groups. The risk of microalbuminuria was significant only in the underweight group (odds ratio, 13.22; 95% confidence interval, 2.55-68.63; P=0.002) after adjusting for confounding factors, abdominal obesity was not significantly associated with microalbuminuria. CONCLUSION: The prevalence of microalbuminuria in a general population in Korea was associated with underweight in men and was not associated with waist circumference in either men or women. PMID- 26885326 TI - Transfusion Related Acute Lung Injury after Cesarean Section in a Patient with HELLP Syndrome. AB - Transfusion-related acute lung injury (TRALI) is a serious adverse reaction of transfusion, and presents as hypoxemia and non-cardiogenic pulmonary edema within 6 hours of transfusion. A 14-year-old primigravida woman at 34 weeks of gestation presented with upper abdominal pain without dyspnea. Because she showed the syndrome of HELLP (hemolysis, elevated liver enzymes, and low platelet count), an emergency cesarean section delivery was performed, and blood was transfused. In the case of such patients, clinicians should closely observe the patient's condition at least during the 6 hours while the patient receives blood transfusion, and should suspect TRALI if the patient complains of respiratory symptoms such as dyspnea. Furthermore, echocardiography should be performed to distinguish between the different types of transfusion-related adverse reactions. PMID- 26885327 TI - Comments on Statistical Issues in January 2016. PMID- 26885325 TI - Association between Obesity and Neighborhood Socioeconomic Status in Korean Adolescents Based on the 2013 Korea Youth Risk Behavior Web-Based Survey. AB - BACKGROUND: An increase in the obese adolescent population is being recognized as a serious medical and social problem. The present study aimed to examine the association between neighborhood socioeconomic status (SES) and obesity in Korean adolescents based on total available resources and local social inequality models. METHODS: The present study used data from the 2013 Korea Youth Risk Behavior Web-based Survey in analyzing 72,438 Korean adolescents aged 12-18. The analysis investigated obesity odds ratio (OR) according to neighborhood SES adjusted for age and individual SES indices, which included family affluence scale (FAS), education level of parents, cohabitation with parents, and weekly allowance. Obesity OR was investigated according to neighborhood SES by FAS, and according to FAS by neighborhood SES. RESULTS: After adjusting for age and individual SES variables, there was no significant association between neighborhood SES and adolescent obesity for either boys or girls. However, girls in the high FAS group showed a pattern of lower neighborhood SES being associated with a significant increase in risk of obesity; in the high neighborhood SES group, boys showed a pattern of higher FAS being associated with a significant increase in risk of obesity, whereas girls show a pattern of decrease. CONCLUSION: Although limited, the present study demonstrated that some girl groups exhibited a pattern of lower neighborhood SES being associated with an increase in risk of obesity, as well as a gender-based difference in risk of obesity by individual SES. Therefore, measures to prevent adolescent obesity should be established with consideration for differences in risk according to individual and neighborhood SES. PMID- 26885328 TI - Prevalence and antimicrobial susceptibility pattern of coagulase-negative staphylococci (CoNS) isolated from clinical specimens in Northern of Jordan. AB - BACKGROUND: Coagulase negative Staphylococci (CoNS) are one of the most common bacteria found on human skin and on mucous membranes as a component of normal flora. The presence of CoNS in clinical specimens is frequently associated with an infectious aetiology or contamination. OBJECTIVES: We aimed to evaluate CoNS species distribution and susceptibility patterns in specimens obtained from clinics and hospitals in the Northern area of Jordan. METHODS: Standard identification methods showed the presence of CoNS in 223 specimens at different local hospitals. Susceptibility testing was performed using 18 antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) recommendations. RESULTS: Staphylococcus epidermidis and S. haemolyticus were found to be the most common species isolated from all specimens representing 122 (54.7%) and 52 (23.4%) of all CoNS species, respectively. Antibiotic susceptibility testing of CoNS species revealed their sensitivity to vancomycin, linozolid, rifampin and nitrofurantin, while showing a highly resistant pattern to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid and erythromycin. Some variation of the susceptibility pattern of CoNS species were identified in specimens isolated from the ICU and paediatric hospital wards as well as from clinical specimens of urine, blood and catheter tips. CONCLUSION: The most common CoNS isolates were found to be S. epidermidis and S. haemolyticus with variable percentages according to the specimen source. Moreover, a high susceptibility CoNS to vancomycin, rifampin, and linezolid showed resistance to amoxicillin and penicillin. PMID- 26885329 TI - Dissemination of Pseudomonas aeruginosa producing bla IMP-1 and bla VIM-1 in Qazvin and Alborz educational hospitals, Iran. AB - BACKGROUND AND OBJECTIVES: Pseudomonas aeruginosa is a frequent opportunistic pathogen in health care associated infections that is highly resistant to the majority of beta-lactams. The aims of this study were to access the antimicrobial susceptibility pattern of P. aeruginosa isolated from educational hospitals of Qazvin and Alborz provinces, to determine the prevalence of metallo-beta lactamase (MBL) among carbapenem non-susceptible isolates by combined disk (CD) method, and to detect the bla IMP, bla VIM, bla SIM, bla GIM, bla SPM and bla NDM 1-MBL genes. MATERIALS AND METHODS: In this cross-sectional study, 300 P. aeruginosa isolates were collected from different clinical specimens in two provinces of Qazvin and Alborz hospitals, Iran. After identification of isolates by standard laboratory methods, antimicrobial susceptibility was done against 17 antibiotics according to clinical and laboratory standards institute (CLSI) guideline. CD method was carried out for detection of MBLs and the presence of bla IMP, bla VIM, bla SIM, bla GIM, bla NDM-1 and bla SPM-genes was further assessed by PCR and sequencing methods. RESULTS: In this study, 107 (35.66%) isolates were non-susceptible to imipenem and/or meropenem among those 56 (52.3%) isolates were metallo-beta-lactamase producer. Twenty-four of 56 (42.85%) MBL positive isolates were confirmed to be positive for MBL-encoding genes in which 14 (25%) and 10 (17.85%) isolates carried bla IMP-1 and bla VIM-1 genes either alone or in combination. Three (5.35%) isolates carried bla IMP and bla VIM genes, simultaneously. CONCLUSION: Considering the moderate prevalence and clinical importance of MBL-producing isolates, rapid identification and use of appropriate infection control (IC) measures are necessary to prevent further spread of infections by these resistant organisms. PMID- 26885330 TI - Hospital acquired diarrhea in a burn center of Tehran. AB - BACKGROUND AND OBJECTIVES: Incidence of hospital-acquired diarrhea has increased rapidly and burn patients are at high risk of getting it. Infection with C. difficile is the most common cause of antibiotic associated diarrhea. The aim of this study was to determine the baseline characteristics and clinical presentation of hospital-acquired diarrhea and compare C. difficile and non-C. difficile diarrhea in burn patients treated at a burn center. MATERIALS AND METHODS: During a 1-year study all patients with hospital-acquired diarrhea at Motahari Burn Hospital, Tehran, Iran enrolled in this study. We compared patients with a stool sample positive for C. difficile toxin or tracing the antigen in patients who were negative for detection of toxin in their stool sample specimens. RESULTS: Diarrhea developed in 37 patients out of 3200 admitted patients with a mean burn size of 34.8 +/-20.1%. Among them, 8 patients had a positive result for C. difficile. The mean time between antibiotic therapy and occurrence of diarrhea was 9.5 +/- 6.2 days. Nine (23.7%) patients died in the 7.8+/- 4.2 days, mostly due to co-morbidities. The mean duration of diarrhea was 3.6 +/- 2 days. Twenty two (57.9%) patients were treated with oral metronidazol and eleven (28.9%) patients were treated with combination of metronidazole and vancomycin, higher rate of combination therapy was seen in Clostridium difficile CDI. CONCLUSION: Overall, the prevalence of hospital-acquired diarrhea was 120/10,000 and 21% of them caused by infection with C. difficile. Presence of peripheral leukocytosis and colitis were the alarm sign for diagnosis of C. difficile infection. PMID- 26885331 TI - Blood pressure alterations in burn patients with septic shock under hydro cortisone treatment. AB - BACKGROUND AND OBJECTIVES: Hydrocortisone is widely used in septic shock cases resistant to fluid and vasopressor therapy. It may result in increased blood pressure and survival. However the efficacy is no established among patients with severe burn and septic shock. Accordingly it was assessed in this study. MATERIALS AND METHODS: The patients older than 14 years of age with resistant septic shock were enrolled during one-year period. The hydrocortisone was prescribed 100 mg three times per day and the alterations in systolic and diastolic blood pressures were recorded. RESULTS: Twenty-nine patients were enrolled including 19 men and 10 women. The mean age was 37 +/- 19 years and the mean burn surface area was 60 +/- 20. Fourteen patients had positive blood culture. The most common isolated microorganism were Pseudomonas aeuroginosa in 34.6%(10 cases), and then Acinetobacter in 13.8%(4 cases). The infection was from wound in 79% and the remaining 21% had pneumonia. Twenty-one patients had good response to hydrocortisone and the increase in systolic and diastolic blood pressures was significant; but the mortality rate was similar. CONCLUSION: Treatment with hydrocortisone would result in increase in systolic and diastolic blood pressure in burn patients with resistant septic shock. PMID- 26885332 TI - Rapid fluorometric quantification of bacterial cells using Redsafe nucleic acid stain. AB - BACKGROUND AND OBJECTIVES: Numerous procedures in biology and medicine require the counting of cells. Direct enumeration of Colony Forming Units (CFUs) is time consuming and dreary accurate cell counting on plates with high numbers of CFUs is error prone. In this study we report a new indirect cell counting method that was developed based on the use of Redsafe fluorometric assay. The usefulness of Redsafe, a nucleic acid stain, in liquid medium is based on the binding of the fluorescent dye to DNA. MATERIALS AND METHODS: Redsafe fluorometric assay was evaluated in comparison with MTT colorimetric assay as a colourimetric assay for enumeration of bacterial cells. RESULTS: Obtained results showed that fluorometric assay threshold for LB grown E. coli is 6*10(4) CFU/ml. Redsafe fluorescent assay can be used as a rapid and inexpensive method for bacterial enumeration and quantification with increased sensitivity. CONCLUSION: The sensitivity of the Redsafe fluorometric assay for detection and enumeration of bacterial cells was 2-log-unit more than that was observed for the MTT assay. PMID- 26885333 TI - Nanosilver-marine fungal chitosan as antibiotic synergizers against sepsis fish bacteria. AB - BACKGROUND AND OBJECTIVES: Mortality is highly variable within population of cultured fish due to virulent bacteria causing fish septicemia. The use of nano silver marine fungal chitosan as antibiotic synergisers could be an alternative in the treatment of sepsis fish pathogens. MATERIALS AND METHODS: Different bulk chitosan solutions were prepared from the mycelia of four marine fungi (Aspergillus terreus, Aspergillus flavipes, Tricoderma hamatum and Fennellia flavipes) and used as capping agents for silver nanoparticles. In vitro, the antibacterial activity of these preparations was determined against nine fish sepsis causing bacteria, alone and in combination with nine antibiotics of choice used in aquaculture. Prepared fungal chitosans (CsF) were characterized by yield of chistosan obtained, degree of deacetylation and viscosity. RESULTS AND CONCLUSION: The maximum yield of chitosan (28%) was obtained from Aspergillus terreus. A. terreus chitosan (CsF), silver nanoparticles (AgNPs) and chitosan silver nanoparticles (CsF-AgNPs) showed maximum activity at the minimum inhibitory concentrations average (MICAVG) 27.2, 18.2 and 7.9 MUg/ml, respectively. Combination of CsF -AgNPs with amikacin (Ak) and rifampicin (RD) reduced the MIC values by 96 and 94%, respectively, with fractional inhibitory concentration index (FICI) = 0.42 and 0.50 as synergistic effect. It is promising to use CsF-AgNPs as enhancing agent in combination with antibiotics for fish sepsis therapy. PMID- 26885334 TI - The prevalence of Pneumocystis jirovecii among patients with different chronic pulmonary disorders in Ahvaz, Iran. AB - BACKGROUND AND OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is a chronic fungal infection that caused by P. jirovecii. Disease is more prevalent among the HIV-infected patients. The colonization of pneumocystis in human respiratory system is associated with the airway inflammation and obstruction. The current study was conducted to identify the prevalence of P. jirovecii among the patients with chronic pulmonary disorders in Ahvaz, Iran. MATERIALS AND METHODS: In the present study, 115 bronchoalveolar lavage (BAL) specimens were collected from patients. Samples were subjected to Nested-PCR with specific primers. The second PCR products were used for sequencing analysis. RESULTS: Our findings demonstrated that 31(27.0%) of samples were positive for P. jirovecii. Nine patients (29%) have tuberculosis (TB) followed by, 1(3.2%) HIV positive and 21(67.7%) miscellaneous pulmonary disorders. Our results show that there was no significant differences between sex (male:female ratio, 17:14), TB, HIV and P. jirovecii in BAL samples (P>0.05). CONCLUSION: The current study is the first report from Ahvaz and it showed a relatively high frequency (27%) of P. jirovecii among patients with different pulmonary disorders. In addition Nested-PCR might be reliable technique for diagnosis of P. jirovecii, while the Grocott's methenamine silver (GMS) have a low sensitivity, which only two positive patients were identified. PMID- 26885335 TI - Microencapsulation of Saccharomyces cerevisiae and its evaluation to protect in simulated gastric conditions. AB - BACKGROUND AND OBJECTIVES: Probiotic yeasts are used in production of functional foods and pharmaceutical products. They play an important role in promoting and maintaining human health. Until now, little work has been published on improving the survival of Saccharomyces in stimulated gastrointestinal condition. MATERIAL AND METHODS: In this study the exposure of the yeast in the capsulate and free forms to artificial gastrointestinal conditions was assessed and the number of viable Saccharomyces cerevisiae cells during 0 to 120 mines in these conditions was evaluated by a pour plate method using sabouraud dextrose agar. RESULTS: Results showed the shape of the beads was generally spherical, sometimes elliptical with a mean diameter of about 50-90 MUm. Also count of viable probiotic cells obtained for all the microcapsules were above the recommended levels for a probiotic food. Also decrease of approximately 4 logs was noted in the number of free cells after 2 h of incubation at pH 2 and 8, when compared to decreases of about 2 logs in the all microencapsulated S. cerevisiae under similar conditions. CONCLUSION: It is concluded that microencapsulation process was significantly able to increase the survival rate of Saccharomyces in a simulated gastrointestinal condition (p<0.05).. PMID- 26885336 TI - Assessment of clinicopathologic features in patients with pituitary adenomas in Northeast of Iran: A 13-year retrospective study. AB - BACKGROUND: Intracranial lesions of the pituitary gland are common pituitary adenomas, accounting for 6-10% of all symptomatic intracranial tumors. In this retrospective study, the clinicopathologic features and survival rate of pituitary adenomas were evaluated. METHODS: The present retrospective study was conducted on 83 patients with pituitary adenomas, referring to radiation oncology departments of Ghaem and Omid Hospitals, Mashhad, Iran, over a period of 13 years (1999-2012). Data obtained from clinical records including clinical features, type of surgery (if performed), treatment modality, overall survival rate, and progression-free survival rate were analyzed. RESULTS: Eighty-three patients including 44 males (53%) and 39 females (47%) participated in this study. The median age was 40 years (age range: 10-69 years). Chiasm compression was reported in 62 patients (74.4%), and 45.78% of the subjects suffered from headaches. Functional and non-functional adenomas were reported in 44 (53.01%) and 39 (46.99%) patients, respectively. In cases with functional and non-functional adenomas, the disease was controlled in 95 and 84.5% of the subjects for 3 years, respectively. Furthermore, 1- and 3-year survival rates for functional adenoma were 84.6 and 23%, respectively; the corresponding values were 90.9 and 22.7% in non-functional adenomas, respectively. CONCLUSION: In this study, a significant correlation between headache severity and type of adenoma was observed. So, application of surgery and radiotherapy together could be a highly effective approach for treating functional adenomas, although it is less efficient for the non-functional type. PMID- 26885337 TI - Mutation analysis in exons 22 and 24 of SCN4A gene in Iranian patients with non dystrophic myotonia. AB - BACKGROUND: Non-dystrophic myotonias are a heterogeneous set of skeletal, muscular channelopathies, which have been associated with point mutations within sodium channel alpha-subunit (SCN4A) gene. Because exons 22 and 24 of SCN4A gene are recognized as hot spots for this disease, the purpose of the study is to identify mutation in exons 22 and 24 of SCN4A gene in Iranian non-dystrophic myotonias patients. METHODS: In this study, 28 Iranian patients with non dystrophic myotonia analyzed for the mutation scanning in exons 22 and 24 of SCN4A gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing. RESULTS: We found 29073G>C substitution in SCN4A gene in one case and 31506A>G substitution in seven cases. The 29073G>C substitution causes a missense mutation G1306A, located in the conserved cytoplasmic loop connecting repeat III and IV of the SCN4A channel but, 31506A>G substitution do not alter amino acid in SCN4A protein. CONCLUSION: G1306A residue is located in functionally important protein region. In "hinged-lid model" for Na(+) channel inactivation in which glycines(1306) act as the hinge of the lid occluding the channel pore. Mutation in this region slowed fast inactivation. Therefore, it might be a pathogenic mutation. The causal relationship of this mutation with the disease is an object for further discussion. PMID- 26885338 TI - Effects of L-arginine pre-treatment in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's diseases in Balb/c mice. AB - BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage. This study aimed to evaluate the effects of L-arginine on the numerical density of dark neurons (DNs) in the SNc of Balb/c mice subjected to MPTP administration. METHODS: In the present study, we demonstrated that repeated treatment with L-arginine (300 mg/kg, i.p.) during 7 consecutive days attenuated the production of DNs in SNc of adult male Balb/c mice infused with a single intranasal administration of MPTP (1 mg/nostril). RESULTS: Pre treatment with L-arginine significantly decreased the numerical density of DNs in SNc of mice 21 days after intranasal MPTP administration. CONCLUSION: This investigation provides new insights in experimental models of PD, indicating that L-arginine represents a potential neuroprotective agent for the prevention of DA neuron degeneration in SNc observed in PD patients. PMID- 26885339 TI - A descriptive study of prevalence, clinical features and other findings of neuromyelitis optica and neuromyelitis optica spectrum disorder in Khuzestan Province, Iran. AB - BACKGROUND: Neuromyelitis optica (NMO) is an uncommon neuro-inflammatory syndrome that has shown to be distinct from multiple sclerosis (MS) and associated with the autoantibody marker NMO-immunoglobulin G (IgG). There are still only a few studies regarding the epidemiology of NMO in Iran. In the present study, we tried to describe the epidemiology of NMO in Khuzestan as one of the densely populated regions in Iran. METHODS: A cross-sectional study was performed during the period 2013-2014. Multiple regional sources of data were used including hospital records, details from neurologists and MS society database. The diagnosis of NMO was based on clinical presentation, abnormal findings on neuroimaging and serological tests. RESULTS: A 51 Caucasian patients (36 patients with NMO and 15 with NMO-spectrum disorder) were identified with a female/male ratio of 7.5:1.0. The crude prevalence of NMO was 1.1/100,000 population. The mean age at onset was 29.2 +/- 6.1 years and the mean duration of symptoms was 5.0 +/- 0.4 years. The majority of patients (60.8%) were classified as having mild disability (Expanded Disability Status Scale = 0-3.5). Among of 35 patients whose titer of NMO-IgG was measured, 19 (54.2%) were seropositive. CONCLUSION: Our study suggests that NMO prevalence rate in South West Iran (Khuzestan Province) is much lower than that reported for MS prevalence rate (16.2/100,000) and our patients had a lower age at onset presentation and milder course of the disease than western countries. PMID- 26885340 TI - Policy interventions to improve rural retention among neurosurgeons in Iran: A discrete choice experiment. AB - BACKGROUND: Health workforce shortages in rural and remote areas are a global challenge that almost every health system has to deal with. This study aimed to discover neurosurgeons' job preferences and propose policy interventions that could possibly increase their retention in rural, remote, or underserved areas. METHODS: A discrete choice experiment (DCE) was conducted in November 2014 with a sample of Iranian neurosurgeons selected from five contrary's provinces representing the geographical diversity. Job attributes included income, dual practice opportunities, workload, proximity to family, clinical infrastructure, housing, educational facilities, and work location. Probit regression model was used to estimate the importance of different job attributes and examine the extent to which neurosurgeons were willing to tradeoff between monetary and nonmonetary attributes. RESULTS: Findings indicated that increased salary, permission to undertake dual practice and access to adequate clinical infrastructure were the most important retention policies. Provision of subsidized housing and educational facilities also increased neurosurgeons' attraction and retention in rural areas. CONCLUSION: A range of policy interventions focusing on both monetary and nonmonetary incentives are required to increase neurosurgeons' retention in rural, remote, or underserved areas. PMID- 26885341 TI - Cortical tumor presenting with Parkinsonism. PMID- 26885342 TI - Cerebellar infarction and aneurysmal subarachnoid hemorrhage: An unusual presentation and rare complications of rhinocerebral mucormycosis. PMID- 26885343 TI - Complicated orolingual angioedema after recombinant tissue plasminogen activator treatment in stroke patients under angiotensin converting enzyme inhibitor: Report of two cases. PMID- 26885344 TI - Nasopharyngeal carcinoma presenting as Garcin's syndrome: A rare case report. PMID- 26885345 TI - The prevalence of Martin-Gruber anastomosis in Iranian subjects by electrodiagnostic criteria. PMID- 26885346 TI - A Scientometric Study of Iranian Scientific Productions in the Field of Substance Use and Addiction Research in the Years 2008 to 2012. AB - BACKGROUND: We aimed to evaluate the current status of scientific production in the field of substance use and addiction in Iran, to determine its trend and pattern during a 5 years period (2008-2012). METHODS: Using relevant keywords, we searched three international databases (Web of Science, Medline, and Scopus) and two local databases (SID and Iranmedex) to locate the papers published in the field of addiction by Iranian researchers during 2008-2012. FINDINGS: The results indicated a significant increase in the number of studies published in the field during the 5 years study period, with more than half of the papers published in the last 2 years. Results also indicated that over half (53.5%) of the papers were published in Persian-language Iranian Journals, but the rate of increase in the number of papers published in English was slightly higher than that of Persian ones. Opioid substances were found to be the topic of approximately 75% of the papers. Studies on key topics, including national surveys, evaluation of current programs, addiction in women and children, and so forth, were found to be highly lacking. CONCLUSION: Results suggested a significant growth in the scientific production of Iran in the field of substance use and addiction. However, considering the significance of substance use and dependence in the country, and compared to the scientific production of developed countries, the amount of research conducted in the field of addiction in Iran is still limited. PMID- 26885347 TI - Assessment of Cognitive Functions in Methadone Maintenance Patients. AB - BACKGROUND: Methadone maintenance has received little scientific attention regarding neurocognitive effects. This study is aimed to assess the neuropsychological performance of methadone maintenance patients (MMP) compared to those healthy controls. METHODS: Thirty-five MMP and 35 healthy controls, matched for age, gender, education and employment status, examined on a battery of tests aimed at assessing verbal fluency, executive functions, verbal memory, and working memory, using controlled oral word association test (COWAT), trial making test (TMT) Part A and B, Rey auditory verbal learning test (RAVLT), and backward digit span. FINDINGS: MMP performed significantly poorly than controls in cognitive domains of verbal fluency, executive function, and verbal memory. MMP did not exhibit impairment in working memory, and TMT Part A compared to controls. CONCLUSION: These results suggest that methadone consumption induces significant cognitive impairment that could compromise drug-treatment outcomes in MMP. PMID- 26885348 TI - Development and Psychometric Properties of Risk and Protective Factors of Substance Use Scale in Iran: An Application of Social Development Model. AB - BACKGROUND: Substance use is a growing public health problem among adolescents. In the lack of a valid and reliable instrument based on social development model (SDM), this study aimed to develop risk and protective factors of substance use scale based on SDM to determine risk and protective factors influencing substance use among adolescents. METHODS: A total of 235 male students from 9th and 10th grade (14-18 years old) of public high schools in Kerman, Iran, selected through multistage cluster sampling. Items pool extracted from the literature and focus groups with male adolescents. Face validity of the questionnaire assessed for readability and clarity of items. Then, an expert panel evaluated the items for content validity. Consequently, construct validity of questionnaire confirmed through exploratory factor analysis (EFA). Known group validity is determined by the degree to which the instrument shows different scores between two groups of those who had an experience in drug use and those who did not have such an experience. In addition, reliability assessed via internal consistency and test retest. FINDINGS: About 10 factor solution (containing 38 items) emerged as a result of EFA entitled adolescent's "beliefs on hookah and alcohol," "bonding to parents," "family rules on substance use," "drug resistance skills," "adolescent's beliefs on hard drugs," "situational perception on hookah and alcohol," "rules of school," "situational perception on hard drugs," "attachment to school," and "perceived opportunity at school." The first four emerged factors explained 46% of the total variance observed. Among these factors, adolescent's beliefs on hookah and alcohol explained a more than 25.3% of the total variance. Results indicated satisfactory internal consistency (Cronbachcs alpha ranging from 0.71 to 0.85) and intra-class correlation coefficients (ICC) (ranging from 0.48 to 0.81). CONCLUSION: The risk and protective factors of substance use questionnaire are the first instrument based on the SDM. The findings showed that this questionnaire is a valid and reliable instrument for assessing determinants of substance use which can be used by researchers and policymakers in preventive initiatives. PMID- 26885349 TI - The Effect of Acute and Chronic Morphine on Some Blood Biochemical Parameters in an Inflammatory Condition in Gonadectomized Male Rats. AB - BACKGROUND: Opiates affect blood factors as well as pain and inflammation in a gender-dependent manner. The aim of the present study was to evaluate the effects of morphine on serum glucose, cholesterol, triglycerides, and urea in gonadectomized and inflammation conditions. METHODS: Animals were divided as follows: control group, carrageenan and chronic morphine recipients, acute morphine recipients, chronic morphine recipients, carrageenan recipients, acute morphine and carrageenan recipients, gonadectomized group, gonadectomized recipients of carrageenan, gonadectomized recipients of morphine, gonadectomized recipients of chronic morphine, gonadectomized recipients of carrageenan and chronic morphine, gonadectomized recipients of acute morphine and carrageenan. FINDINGS: Our results have shown that acute and chronic morphine elevates blood glucose level in the acute and chronic morphine group. Cholesterol level has shown to be increasing in the morphine and carrageenan recipient group compared with a group which merely received morphine. Triglyceride has shown to be decreasing in acute and chronic morphine recipient group compared with control group. A significant increase in serum urea was observed in acute and chronic morphine recipients compared with the carrageenan recipient group. CONCLUSION: Morphine alters the serum glucose, cholesterol, triglyceride, and urea in the normal and inflammatory conditions differently, hence, this finding should be considered in the patients who use morphine as a relief of pain, especially in an inflammatory condition. PMID- 26885350 TI - Frequency of Psychiatric Disorders in Children of Opioid or Methamphetamine Dependent Patients. AB - BACKGROUND: Addiction is one of the main problems of human societies, which is more common in developing countries. In addition, it causes to personal and social problems and family problem. The aim of this study was to examine the prevalence of psychiatric disorders in children 5-15 years old of opioid or methamphetamine dependence patients. METHODS: For this study, three groups including: (1) children of parents addicted to opium, (2) children of parents addicted to methamphetamine, and (3) control group were examined. Child symptom inventory-4 (CSI-4) questionnaires completed by non-hospitalized guardian and control group; then make interviews with the children by the Kiddie-schedule for affective disorders and schizophrenia (K-SADS). Data were analyzed by chi-square test and ANOVA. FINDINGS: Survey showed that the frequency of attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), generalized anxiety disorder, obsessive-compulsive disorder, specific phobia (SP), and separation anxiety disorder in children of addicted parents were more than a non addicted parent. However, there was no significant difference between the two groups in the frequency of conduct disorder, social phobia, and oppositional defiant disorders (ODDs). CONCLUSION: Parental addiction can lead to an increase in some psychiatric disorders in the children. Therefore follow-up, early diagnosis, treatment, and prevention of these disorders in children of the drug dependent parent are necessary to reduce health costs and improve the health system. PMID- 26885351 TI - Elevated Plasma Homocysteine Concentration in Opium-Addicted Individuals. AB - BACKGROUND: Although the triggering role of both opium use and elevated plasma homocysteine level for progressing atherosclerosis and, therefore, appearing coronary heart disease has been clearly determined, no study are available with respect to the relation between these to risk profiles. In the present study and for the first time, we hypothesized that the opium addiction can be potentially correlated with elevated homocysteine concentration. METHODS: 217 persons (103 opium-addicted and 114 non-addicted) were randomly selected from the Kerman Coronary Artery Disease Risk Study (KERCADRS), Iran, as a population-based, epidemiological prospective study. In all participants, an enzyme immunoassay kit was used to measure homocysteine in serum samples. FINDINGS: The serum level of homocysteine was significantly higher in the opium-addicted ones compared to non addicted individuals (11.49 +/- 7.45 vs. 8.02 +/- 3.87 MUmol/l) (P < 0.001). In this regard, 21.3% of the opium users and only 3.2% of the non-users had homocysteine concentration > 15 MUmol/l (P < 0.001). On the other hand, individuals addicted to opiates exhibited significantly elevated odds of having homocysteine level higher than 15 [odds ratio (OR) = 8.244, 95% confidence interval (CI) = 3.117-21.806]. Multivariable linear regression model showed that the opium addiction could strongly predict elevated homocysteine level in the study individuals [beta = 3.524, standard error (SE) = 0.852] (P < 0.001). CONCLUSION: Opium consumption can be strongly accompanied with the elevation of plasma homocysteine concentration, and thus opium addiction can exhibit elevated odds of having hyperhomocysteinemia. PMID- 26885352 TI - The Value of Perfectionism in Predicting Coping Strategies in Drug-User Women. AB - BACKGROUND: Positive perfectionism helps the individual to experience fewer worries and less anxiety. The aim of the present study was to assess the value of coping strategies to predict perfectionism in drug-user women. METHODS: This cross-sectional study was performed on 361 consecutive drug-user women who were randomly selected from a total of 6237 women referring to the Drug Abuse Centers of Kerman, Iran, in 2013. Data were gathered using the positive and negative perfectionism scale, and coping responses questionnaire. FINDINGS: There were significant correlations between positive and negative perfectionism with coping strategies problem-focused and emotional-focused (P < 0.001). Using multivariate regression modeling, 12% of total mental health variances could be estimated from metacognition beliefs. CONCLUSION: The positive and negative perfectionism can be rolled both as the predictors of coping strategies in drug-user women. PMID- 26885354 TI - Comparing Sensory Information Processing and Alexithymia between People with Substance Dependency and Normal. AB - BACKGROUND: Sensory information processing and alexithymia are two important factors in determining behavioral reactions. Some studies explain the effect of the sensitivity of sensory processing and alexithymia in the tendency to substance abuse. Giving that, the aim of the current study was to compare the styles of sensory information processing and alexithymia between substance dependent people and normal ones. METHODS: The research method was cross sectional and the statistical population of the current study comprised of all substance-dependent men who are present in substance quitting camps of Masal, Iran, in October 2013 (n = 78). 36 persons were selected randomly by simple randomly sampling method from this population as the study group, and 36 persons were also selected among the normal population in the same way as the comparison group. Both groups was evaluated by using Toronto alexithymia scale (TAS) and adult sensory profile, and the multivariate analysis of variance (MANOVA) test was applied to analyze data. FINDINGS: The results showed that there are significance differences between two groups in low registration (P < 0.020, F = 5.66), sensation seeking (P < 0.050, F = 1.92), and sensory avoidance (P < 0.008, F = 7.52) as a components of sensory processing and difficulty in describing emotions (P < 0.001, F = 15.01) and difficulty in identifying emotions (P < 0.002, F = 10.54) as a components of alexithymia. However, no significant difference were found between two groups in components of sensory sensitivity (P < 0.170, F = 1.92) and external oriented thinking style (P < 0.060, F = 3.60). CONCLUSION: These results showed that substance-dependent people process sensory information in a different way than normal people and show more alexithymia features than them. PMID- 26885355 TI - Comparison of Cotinine Salivary Levels in Hookah Smokers, Passive Smokers, and Non-Smokers. AB - BACKGROUND: At present smoking is considered a great health-related problem. Smoking cigarettes and use of tobacco are on the rise in the Middle East countries; therefore, the number of people exposed to passive cigarette smoke is increasing, too. The aim of the present study was to determine and compare salivary cotinine levels in hookah smokers, individuals exposed to passive cigarette smoke and non-smoker (passive smokers). METHODS: In the present cross sectional study, unstimulated salivary samples were collected from 150 subjects, including 50 hookah smokers, 50 passive smokers, and 50 non-smokers. Bioassay Technology Laboratory cotinine kit was used to determine salivary levels of cotinine using the enzyme-linked immunosorbent assay (ELISA) technique at a sensitivity rate of 0.019 pg/ml. Data were analyzed with SPSS software using t test and Pearson's correlation coefficient. FINDINGS: The highest salivary cotinine levels were recorded in hookah users (20.24 +/- 5.62 ng/ml), followed by passive smokers (16.09 +/- 3.51 ng/ml), in descending order. No detectable cotinine levels were observed in non-smokers. Pearson's correlation coefficient showed a strong and positive correlation between use of hookah and salivary cotinine levels (r = 0.932, P = 0.001). CONCLUSION: Based on the results of the present study, salivary cotinine levels were higher in hookah smokers compared with passive smokers and non-smokers, in descending order. PMID- 26885356 TI - The Role of Depression and Attachment Styles in Predicting Students' Addiction to Cell Phones. AB - BACKGROUND: The present study aimed at investigating the role of depression and attachment styles in predicting cell phone addiction. METHODS: In this descriptive correlational study, a sample including 100 students of Payame Noor University (PNU), Reyneh Center, Iran, in the academic year of 2013-2014 was selected using volunteer sampling. Participants were asked to complete the adult attachment inventory (AAI), Beck depression inventory-13 (BDI-13) and the cell phone overuse scale (COS). FINDINGS: Results of the stepwise multiple regression analysis showed that depression and avoidant attachment style were the best predictors of students' cell phone addiction (R(2) = 0.23). CONCLUSION: The results of this study highlighted the predictive value of depression and avoidant attachment style concerning students' cell phone addiction. PMID- 26885353 TI - Client-Level Coverage of Needle and Syringe Program and High-Risk Injection Behaviors: A Case Study of People Who Inject Drugs in Kermanshah, Iran. AB - BACKGROUND: Needle-syringe programs (NSP) have been running in Iran since 2002. However, the coverage of such program among the NSP clients at the individual level was not studies yet. This study aimed to determine the client coverage of NSP and its correlation with high injection-related risk behaviors. METHODS: A cross-sectional survey was conducted in Kermanshah province, Iran, in 2014. 230 people who inject drugs (PWID) recruited from two drop-in centers (DICs) from April to September 2014, participated in a face-to-face interview to provide information related individual coverage of NSP, demographic characteristics, and injecting behaviors 30 days prior to the interview. FINDINGS: Overall, the average of syringe coverage was 158% [95% confidence interval (CI) = 65.7-205.5], while 56% (95% CI = 40-97) have individual converge less than 100%. Needle/syringe sharing was significantly higher among individual with low NSP coverage [adjusted odds ratio (AOR) = 2.6, 95% CI = 1.3-6.2]. About 85% participants with coverage of less than 100% reported reuse of syringe within the last 30 days (AOR = 3.2, 95% CI = 1.4-7.7). CONCLUSION: PWID are different regarding their NSP individual-level converges. There are certain clusters of PWID, who do not receive sufficient number of syringes. Given that insufficient individual syringe coverage level is highly associated with injection risk behaviors, reasons for such low converge need to be assessed and addressed carefully. PMID- 26885357 TI - What Is the Main Reason for Reduction in Duration of Action of Local Anesthetics Used for Spinal Anesthesia in Opium Addicted Patients? PMID- 26885358 TI - An investigation of the associations among sleep duration and quality, body mass index and insulin resistance in newly diagnosed type 2 diabetes mellitus patients. AB - OBJECTIVES: To examine direct and indirect associations of sleep duration and quality with insulin resistance, considering body mass index (BMI) as a potential mediator in newly diagnosed type 2 diabetes mellitus patients. METHODS: Cross sectional data from patients enrolled in the Early Activity in Diabetes study. We studied 522 newly diagnosed type 2 diabetes mellitus patients, 65.9% male, mean age 63.5 +/- 10.1 years. Of the total sample 53% had a BMI of ?30 kg/m(2). Participants completed a 7-day sleep diary and sleep questionnaire. Average sleep duration (minutes), average nap duration (minutes) and average number of night awakenings were derived. Objective measures of height and body weight were obtained for the BMI calculation (kg/m(2)). Insulin resistance was obtained using the homeostatic model assessment - insulin resistance (HOMA2-IR) standardized technique. RESULTS: Average number of night awakenings was positively correlated with BMI (r= 0.22, p < 0.001) and negatively associated with logged HOMA2-IR (r= 0.16, p = 0.04). Path analysis demonstrated night awakenings were directly associated with BMI and indirectly associated with insulin resistance, whilst considering BMI as a potential mediator (p < 0.05). Sleep duration was not associated with BMI or insulin resistance (p > 0.05). CONCLUSIONS: Sleep quality, not sleep duration, plays an important role in insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMI may mediate the relationship between indicators of sleep quality and insulin resistance. There is a need to examine the impact of improving sleep quality on obesity and insulin resistance in patients with type 2 diabetes mellitus. PMID- 26885359 TI - Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits. AB - Subclinical hypothyroidism (SCH) is defined as elevated thyroid stimulating hormone (TSH) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). SCH is further classified into a milder condition with TSH levels between 4.0 and 10.0 milli-international units (mIU)/l (mild-SCH) and a severe form with TSH >10.0 mIU/l (severe-SCH). SCH is a common problem (prevalence is greater in women than men), which increases further with increasing age and TSH levels. Even though the risk of progression to overt hypothyroidism is higher in patients with severe-SCH, the risk is also significant in patients having mild-SCH; it has been suggested that every twofold rise in serum TSH would increase the risk from 1 to 4%, which further increases to 38% if thyroid antibodies are positive. Current data have shown increased cardiovascular risk in patients with mild-SCH and have demonstrated some benefits of levothyroxine treatment in reducing these events. However, evidence on the association of mild-SCH and musculoskeletal system, cognitive dysfunction, mood disorders, dyslipidaemia, diabetes and goitre is conflicting. Similarly, the discussion regarding the exact upper limit of normal for serum TSH remains controversial. The data have also shown increased risk of adverse pregnancy outcomes in patient with mild-SCH, with some benefits of thyroxine treatment. The recent available guidelines related to management of patients with serum TSH <10 mIU/l have suggested decisions should be made taking into account the age of the patient, associated risk factors and comorbid conditions. This chronicle review assesses current evidence regarding the risks associated and the recommendations related to benefits of levothyroxine treatment in patients having mild-SCH. PMID- 26885361 TI - Consecutive lynestrenol and cross-sex hormone treatment in biological female adolescents with gender dysphoria: a retrospective analysis. AB - BACKGROUND: Prior to the start of cross-sex hormone therapy (CSH), androgenic progestins are often used to induce amenorrhea in female to male (FtM) pubertal adolescents with gender dysphoria (GD). The aim of this single-center study is to report changes in anthropometry, side effects, safety parameters, and hormone levels in a relatively large cohort of FtM adolescents with a diagnosis of GD at Tanner stage B4 or further, who were treated with lynestrenol (Orgametril(r)) monotherapy and in combination with testosterone esters (Sustanon(r)). METHODS: A retrospective analysis of clinical and biochemical data obtained during at least 6 months of hormonal treatment in FtM adolescents followed at our adolescent gender clinic since 2010 (n = 45) was conducted. McNemar's test to analyze reported side effects over time was performed. A paired Student's t test or a Wilcoxon signed-ranks test was performed, as appropriate, on anthropometric and biochemical data. For biochemical analyses, all statistical tests were done in comparison with baseline parameters. Patients who were using oral contraceptives (OC) at intake were excluded if a Mann-Whitney U test indicated influence of OC. RESULTS: Metrorrhagia and acne were most pronounced during the first months of monotherapy and combination therapy respectively and decreased thereafter. Headaches, hot flushes, and fatigue were the most reported side effects. Over the course of treatment, an increase in musculature, hemoglobin, hematocrit, creatinine, and liver enzymes was seen, progressively sliding into male reference ranges. Lipid metabolism shifted to an unfavorable high-density lipoprotein (HDL)/low-density lipoprotein (LDL) ratio; glucose metabolism was not affected. Sex hormone-binding globulin (SHBG), total testosterone, and estradiol levels decreased, and free testosterone slightly increased during monotherapy; total and free testosterone increased significantly during combination therapy. Gonadotropins were only fully suppressed during combination therapy. Anti Mullerian hormone (AMH) remained stable throughout the treatment. Changes occurred in the first 6 months of treatment and remained mostly stable thereafter. CONCLUSIONS: Treatment of FtM gender dysphoric adolescents with lynestrenol monotherapy and in combination with testosterone esters is effective, safe, and inexpensive; however, suppression of gonadotropins is incomplete. Regular blood controls allow screening for unphysiological changes in safety parameters or hormonal levels and for medication abuse. PMID- 26885362 TI - Allergen immunotherapy for insect venom allergy: protocol for a systematic review. AB - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT. PMID- 26885363 TI - Sick leave and healthcare utilisation in women reporting pregnancy related low back pain and/or pelvic girdle pain at 14 months postpartum. AB - BACKGROUND: Pregnancy related low back pain (PLBP) and pelvic girdle pain (PGP) are considered common complications of pregnancy. The long-term consequences for women with persistent PLBP/PGP postpartum are under-investigated. The main objective was to investigate the prevalence, pattern and degree of sick leave as well as healthcare utilisation and its perceived effect in women with persistent PLBP/PGP at 12 months postpartum. METHOD: This is a follow-up study of a cohort involving of a sample of women, who delivered from January 1(st) 2002 to April 30(th) in 2002 at Umea University Hospital and Sunderby Hospital, and who reported PLBP/PGP during pregnancy. A total of 639 women were followed-up by a second questionnaire (Q2) at approximately 6 months postpartum. Women with persistent PLBP/PGP at the second questionnaire (N = 200) were sent a third questionnaire (Q3) at approximately 12 months postpartum. RESULTS: The final study sample consisted of 176 women reporting PLBP/PGP postpartum where N = 34 (19.3 %) reported 'no' pain, N = 115 (65.3 %) 'recurrent' pain, and N = 27 (15.3 %) 'continuous' pain. The vast majority (92.4 %) of women reported that they had neither been on sick leave nor sought any healthcare services (64.1 %) during the past 6 months at Q3. Women with 'continuous' pain at Q3 reported a higher extent of sick leave and healthcare seeking behaviour compared to women with 'recurrent' pain at Q3. Most women with persistent PLBP/PGP had been on sick leave on a full time basis. The most commonly sought healthcare was physiotherapy, followed by consultation with a medical doctor, acupuncture and chiropractic. CONCLUSION: Most women did not report any sick leave or sought any healthcare due to PLBP/PGP the past 6 months at Q3. However, women with 'continuous' PLBP/PGP 14 months postpartum did report a higher prevalence and degree of sick leave and sought healthcare to a higher extent compared to women with 'recurrent' PLBP/PGP at Q3. Women with more pronounced symptoms might constitute a specific subgroup of patients with a less favourable long-term outcome, thus PLBP/PGP needs to be addressed early in pregnancy to reduce both individual suffering and the risk of transition into chronicity. PMID- 26885364 TI - Correlation between biofilm formation and resistance toward different commonly used antibiotics along with extended spectrum beta lactamase production in uropathogenic Escherichia coli isolated from the patients suspected of urinary tract infections visiting Shree Birendra Hospital, Chhauni, Kathmandu, Nepal. AB - BACKGROUND: Escherichia coli is the most predominant causative agent of urinary tract infection (UTI). Recently, increase in drug resistance among the uropathogenic bacteria has caused great problem in treatment of UTI. The main objective of this research is to determine the correlation between biofilm formation and resistance toward different commonly used antibiotics along with extended spectrum beta lactamase production in uropathogenic Escherichia coli. METHODS: The urine samples collected from the patients suspected of urinary tract infections (visiting Shree Birendra Hospital, Chhauni, Kathmandu, Nepal between July to December 2013) were cultured in cystine lactose electrolyte deficient (CLED) agar by using semi quantitative culture technique. Extended spectrum beta lactamase (ESBL) production was detected by combined disc diffusion technique and biofilm formation was detected by Congo red agar method. Chi-square test was applied and p-value < 0.05 was considered statistically significant. RESULTS: Out of 1480 urine samples, E. Coli was isolated from 208 (14.1 %) samples. Of total 69 (33.2 %) ESBL producing uropathogenic strains of E. coli, 20 (29 %) were strong biofilm producers, 22 (31.9 %) were moderate biofilm producers, 11 (15.9 %) were weak biofilm producers and 16 (23.2 %) were biofilm non producers. Whereas among 139 ESBL non producing E. coli, 22 (15.8 %) were strong biofilm producers, 20 (14.4 %) were moderate biofilm producers, 13 (9.4 %) were weak biofilm producers and 84 (60.4 %) were biofilm non producers. Among total 108 biofilm producing E. coli, maximum resistance was observed toward cephalexin followed by amoxicillin and highest susceptibility was seen toward amikacin. CONCLUSION: The ability of biofilm formation was found to be significantly higher in ESBL producing strains of E. coli than that in ESBL non producing strains (p < 0.05). There was higher resistance rate to antimicrobial agents among biofilm producing strains of E. coli than that in biofilm non producing strains. According to our antimicrobial susceptibility pattern for E. coli, to start preliminary treatment for UTI in Nepal, we recommend to use amikacin or nitrofurantoin. Further, for the treatment of the UTI, the antibiotics should be selected on the basis of the urine culture and sensitivity report. PMID- 26885365 TI - Erratum to: Particulate matters from diesel heavy duty trucks exhaust versus cigarettes emissions: a new educational antismoking instrument. AB - [This corrects the article DOI: 10.1186/s40248-016-0042-7.]. PMID- 26885360 TI - Stimulation of incretin secreting cells. AB - The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon like peptide-1 (GLP-1) are secreted from enteroendocrine cells in the gut and regulate physiological and homeostatic functions related to glucose control, metabolism and food intake. This review provides a systematic summary of the molecular mechanisms underlying secretion from incretin cells, and an understanding of how they sense and interact with lumen and vascular factors and the enteric nervous system through transporters and G-protein coupled receptors (GPCRs) present on their surface to ultimately culminate in hormone release. Some of the molecules described below such as sodium coupled glucose transporter 1 (SGLT1), G-protein coupled receptor (GPR) 119 and GPR40 are targets of novel therapeutics designed to enhance endogenous gut hormone release. Synthetic ligands at these receptors aimed at treating obesity and type 2 diabetes are currently under investigation. PMID- 26885367 TI - Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds. AB - The long-standing promise for the application of engineered T lymphocytes to target and eradicate malignancy has begun to be realized recently, with remarkable clinical success reported by a number of groups using Chimeric Antigen Receptor -engineered T cells to target CD19-positive hematologic malignancies. In the September 2 issue of Science Translational Medicine, Porter et al. present the clinical data and correlative analyses for 14 CLL patients treated at the University of Pennsylvania under the pilot clinical trial recently completed at that institution. The initial reports from this trial, published in 2011 documented robust clinical activity in a small cohort of treated patients accompanied by logarithmic expansion, contraction, and long-term functional persistence of engineered T cells, along with cytokine release syndrome as a side effect of the treatment. In this latest report, updated data are presented from the initial cohort of patients, as well as clinical and correlative data from the remainder of the treated cohort. The robust clinical activity observed in the initial cohort continued to be observed in a subset of the subsequently-treated patients, with molecular remissions documented in that subset; however, in the expanded cohort a subset of partial and non-responding patients was also identified. Collectively, the results from this exciting trial provide evidence to suggest that cellular immunotherapy using engineered T cells is a viable option for treating CLL, reveal a likely requirement for robust in-vivo activation and persistence of engineered cells to effect complete responses, and also highlight the need for a more complete mechanistic understanding of the immune- and tumor- specific processes that define and dictate the success of this powerful treatment modality. PMID- 26885366 TI - Metabolic communication in tumors: a new layer of immunoregulation for immune evasion. AB - The success of cancer immunotherapy reveals the power of host immunity on killing cancer cells and the feasibility to unleash restraints of anti-tumor immunity. However, the immunosuppressive tumor microenvironment and low immunogenicity of cancer cells restrict the therapeutic efficacy of cancer immunotherapies in a small fraction of patients. Therefore deciphering the underlying mechanisms promoting the generation of an immunosuppressive tumor microenvironment is direly needed to better harness host anti-tumor immunity. Early works revealed that deregulated metabolic activities in cancer cells support unrestricted proliferation and survival by producing macromolecules. Intriguingly, recent studies uncovered that metabolic switch in immune and endothelial cells modulate cellular activities and contribute to the progression of several diseases, including cancers. Herein, we review the progress on immunometabolic regulations on fine-tuning activities of immune cells and discuss how metabolic communication between cancer and infiltrating immune cells contributes to cancer immune evasion. Moreover, we would like to discuss how we might exploit this knowledge to improve current immunotherapies and the unresolved issues in this field. PMID- 26885368 TI - Toll-like receptor agonist therapy can profoundly augment the antitumor activity of adoptively transferred CD8(+) T cells without host preconditioning. AB - BACKGROUND: Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation injured gut. Microbial components, such as LPS, are key mediators of total body irradiation (TBI) enhancement, but our ability to strategically use these toll like receptor (TLR) agonists to bolster the potency of T cell-based therapies for cancer remains elusive. Herein, we used TLR4 agonist LPS as a tool to address how and when to use TLR agonists to effectively improve cancer immunotherapy. METHODS: To determine the mechanisms of how innate immune activation via lymphodepletion potentiated antitumor T cell immunity, we utilized the pmel-1 melanoma mouse model. B16F10-bearing mice were preconditioned with 5Gy TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD8(+) T cells, vaccination with fowlpox encoding gp100, and IL-2) along with TLR4 agonist LPS. The timing of LPS administration and the requirement of individual components of the tripartite therapy were evaluated based on tumor growth and the phenotype of recovered splenocytes by flow cytometry. We also evaluated the role of non-toxic and clinically used TLR4 and TLR9 agonists-monophosphoryl lipid A (MPL) and CpG Oligodeoxynucleotide (CpG ODN), respectively- for ACT therapy. RESULTS: Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8(+) T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. Moreover, we found that sequentially administering LPS during or one day prior to ACT therapy compromised tumor regression. In contrast, administering LPS after ACT potentiated the antitumor effectiveness of the regimen, thereby supporting the expansion of transferred tumor-specific CD8(+) T cells over host CD4(+) T cells. We also found that non-toxic TLR agonists MPL and CpG potentiated the antitumor activity of infused CD8(+) T cells. Finally, TBI was no longer needed to regress tumors in mice who were depleted of host CD4(+) T cells, given a tripartite ACT regimen and then treated with low dose LPS. CONCLUSIONS: Collectively, our results identify how and when to administer TLR agonists to augment T cell-based immunotherapy in the absence or presence of host preconditioning for treatment of advanced malignancies. Our findings have clinical implications for the design of next generation immune-based therapies for patients with cancer. PMID- 26885370 TI - Autoimmune inner ear disease in a melanoma patient treated with pembrolizumab. AB - BACKGROUND: Immune related adverse events affecting various organ systems are a recognized potential consequence of immune checkpoint inhibition. However, autoimmune inner ear disease is one complication not previously associated with the use of checkpoint inhibitors, though it has been reported after adoptive cell immunotherapy. CASE PRESENTATION: Here we present what we believe is the first case of autoimmune inner ear disease resulting from treatment with an immune checkpoint inhibitor in a patient with metastatic melanoma. An 82 year old male presented with widespread metastatic mucosal melanoma and was initially treated with the CTLA-4 inhibitor ipilimumab but had progression of disease after four doses. He was subsequently treated with the PD-1 inhibitor pembrolizumab and after two doses the patient noted bilateral hearing loss. Otology evaluation was significant for the development of bilateral sensorineural hearing loss and the patient was started on treatment with bilateral intratympanic dexamethasone injections. He experienced significant recovery of his hearing deficit with the intratympanic injections and restaging imaging after 12 weeks of pembrolizumab demonstrated a dramatic reduction in tumor burden. CONCLUSION: Autoimmune inner ear disease has been previously associated with the therapeutic transfer of genetically engineered lymphocytes as an on-target effect of donor T-cells recognizing antigens on cells in the inner ear. It is important for physicians to have a high clinical index of suspicion for the appropriate recognition and management of any potential autoimmune toxicity with checkpoint inhibitors given the variability of presentation and unique aspects of toxicity. PMID- 26885371 TI - Multiplexed tissue biomarker imaging. PMID- 26885372 TI - Mismatch in epitope specificities between IFNgamma inflamed and uninflamed conditions leads to escape from T lymphocyte killing in melanoma. AB - BACKGROUND: A current focus in cancer treatment is to broaden responses to immunotherapy. One reason these therapies may prove inadequate is that T lymphocytes fail to recognize the tumor due to differences in immunogenic epitopes presented by the cancer cells under inflammatory or non-inflammatory conditions. The antigen processing machinery of the cell, the proteasome, cleaves proteins into peptide epitopes for presentation on MHC complexes. Immunoproteasomes in inflammatory melanomas, and in antigen presenting cells of the immune system, are enzymatically different to standard proteasomes expressed by tumors with no inflammation. This corresponds to alterations in protein cleavage between proteasome subtypes, and a disparate repertoire of MHC-presented epitopes. METHODS: We assessed steady state and IFNgamma-induced immunoproteasome expression in melanoma cells. Using epitope specific T-lymphocyte clones, we studied processing and presentation of three NY-ESO-1 HLA-Cw3 restricted epitopes by melanoma cell lines. Our experimental model allowed comparison of the processing of three distinct epitopes from a single antigen presented on the same HLA complex. We further investigated processing of these epitopes by direct inhibition, or siRNA mediated knockdown, of the immunoproteasome catalytic subunit LMP7. RESULTS: Our data demonstrated a profound difference in the way in which immunogenic T-lymphocyte epitopes are presented by melanoma cells under IFNgamma inflammatory versus non-inflammatory conditions. These alterations led to significant changes in the ability of T-lymphocytes to recognize and target melanoma cells. CONCLUSIONS: Our results illustrate a little-studied mechanism of immune escape by tumor cells which, with appropriate understanding and treatment, may be reversible. These data have implications for the design of cancer vaccines and adoptive T cell therapies. PMID- 26885373 TI - Monomeric annexin A2 is an oxygen-regulated toll-like receptor 2 ligand and adjuvant. AB - BACKGROUND: Annexin A2 (ANXA2) is a pleiotropic, calcium-dependent, phospholipid binding protein with a broad tissue distribution. It can be intracellular, membrane-bound, or secreted, and it exists as a monomer or heterotetramer. The secreted ANXA2 heterotetramer signals human and murine macrophages to produce IL 1, IL-6, and TNF-alpha through TLR4/MyD88- and TRIF-dependent pathways. METHODS: GL261 glioma cells were cultured in 5 % or 20 % O2. Monomeric ANXA2 (ANXA2m) was identified as a TLR2-binding protein enriched in 5 % O2 by mass spectrometry. Purified ANXA2m and ANXA2-derived peptides were added to TLR2-expressing reporter cells and immature dendritic cells (DCs) cells in vitro. ANXA2m was then mixed with chicken ovalbumin (OVA) for vaccination of TLR2 (+/+) and TLR2 (-/-) mice for subsequent quantification of antigen-specific CD8(+) T cell responses. The TLR2-binding region of ANXA2m was determined using various peptides derived from the ANXA2 amino terminus on TLR2 reporter cells and in vaccinated mice. RESULTS: ANXA2m is overexpressed by murine glioblastoma GL261 cells grown under 5 % O2, but not atmospheric 20 % O2, and acts as an adjuvant by inducing murine and human DC maturation through TLR2. ANXA2m upregulates CD80 and CD86 expression, enhances antigen cross-presentation, and induces the secretion of IL-12p70, TNF-alpha, and IFN-gamma. The amino-terminal 15 amino acids of ANXA2m are necessary and sufficient for TLR2 binding and DC activation. CONCLUSION: This novel finding adds to the known functions of ANXA2 and suggests ways to exploit it as a vaccine adjuvant. ANXA2-antigen fusion peptides could be developed for patients as "off the-shelf" agents containing common tumor antigens. Alternatively, they could be "personalized" and synthesized after tumor sequencing to identify immunogenic tumor-specific neo-antigens. As the amino terminal 15 amino acids of ANXA2 are required to stimulate TLR2 activity, a fusion peptide could be as short as 30 amino acids if one or two CD8 T cell epitopes are fused to the ANXA2 amino terminal portion. Future work will address the efficacy of ANXA2 peptide fusions alone and in combination with established TLR agonists to induce synergy in preclinical models of glioma as observed in other vaccines. PMID- 26885377 TI - Recent advances in canola meal utilization in swine nutrition. AB - Canola meal is derived from the crushing of canola seed for oil extraction. Although it has been used in swine diets for a long time, its inclusion levels have been limited due to concerns regarding its nutritive value primarily arising from results of early studies showing negative effects of dietary canola meal inclusion in swine diets. Such effects were attributable to the presence of anti nutritional factors (ANF; notably glucosinolates) in canola meal. However, due to advances in genetic improvements of canola that have led to production of cultivars with significantly lower ANF content and improved processing procedures, canola meal with a superior nutritive value for non-ruminant animals is now available. Therefore, the aim of this paper is to review the recent studies in the use of canola meal as feedstuff for swine, the factors influencing its use and the strategies to overcome them. First a historical overview of the development of canola is provided. PMID- 26885374 TI - A comparison of behavioral and psychological characteristics of patients opting for surgical and conservative treatment for morbid obesity. AB - BACKGROUND: Little is known about the psychological prerequisites for weight loss maintenance after bariatric surgery. A first step in investigating whether existing knowledge of conservative weight loss treatment is applicable for lifestyle interventions postoperatively is to compare specific psychological characteristics at baseline. The aim of this study was to compare patients scheduled for bariatric surgery with patients receiving conservative treatment for morbid obesity on measures of behavioral and psychosocial characteristics considered predictors of their adoption of and adherence to long-term lifestyle recommendations. METHODS: Baseline clinical and questionnaire data from the prospective "Oslo Bariatric Surgery Study" were used to examine potential differences between bariatric surgery patients (n = 301) and patients receiving conservative weight loss treatment (n = 261). RESULTS: The surgical group was characterized by their younger age (43.8 vs. 46.2 years, p <0.01), higher percentage of women (79.1 vs. 70.1 %, p <0.05), and higher Body Mass Index (BMI; 45.0 vs. 41.9 kg/m(2), p <0.001). A multiple logistic regression analysis, adjusting for group differences in BMI, gender, and age, showed that the surgical group had higher self-efficacy (Odds ratio; OR = 3.44, 95 % Confidence interval; CI 1.65, 7.14), more positive outcome expectations (OR = 1.53, 95 % CI 1.23, 1.89), and plans that were more explicit for changing their eating behaviors (OR = 1.80, 95 % CI 1.06, 1.93). The surgical patients were also less ready to change physical activity levels (OR = 0.59, 95 % CI 0.48, 0.73), had tried more types of unhealthy weight loss methods in the past (OR = 1.16, 95 % CI 1.01, 1.33), drank soda more frequently (OR = 1.24, 95 % CI 1.02, 1.50), had fewer binge eating episodes (OR = 0.38, 95 % CI 0.20, 0.71), and had more depressive symptoms (OR = 1.19, 95 % CI 1.09, 1.29). CONCLUSIONS: Patients opting for bariatric surgery had more positive expectations of the treatment outcomes and stronger beliefs in their ability to achieve these outcomes. Those starting conservative treatment had stronger beliefs in readiness to change physical activity levels. Future studies should explore the effect of interventions for bariatric surgery patients, promoting postoperative physical activity and stress realistic outcome expectations. The potential effects of incorporating this knowledge in intervention strategies remain to be explored. PMID- 26885378 TI - Intraoperative Corneal Thickness Changes during Pulsed Accelerated Corneal Cross Linking Using Isotonic Riboflavin with HPMC. AB - Purpose. To evaluate corneal thickness changes during pulsed accelerated corneal cross-linking (CXL) for keratoconus using a new isotonic riboflavin formula. Methods. In this prospective, interventional, clinical study patients with grades 1-2 keratoconus (Amsler-Krumeich classification) underwent pulsed accelerated (30 mW/cm(2)) CXL after application of an isotonic riboflavin solution (0.1%) with HPMC for 10 minutes. Central corneal thickness (CCT) measurements were taken using ultrasound pachymetry before and after epithelial removal, after riboflavin soaking, and immediately after completion of UVA treatment. Results. Twenty eyes of 11 patients (4 males, 7 females) were enrolled. Mean patient age was 26 +/- 3 (range from 18 to 30 years). No intraoperative or postoperative complications were observed in any of the patients. Mean CCT was 507 +/- 35 MUm (range: 559-459 MUm) before and 475 +/- 40 MUm (range: 535-420 MUm) after epithelial removal (P < 0.001). After 10 minutes of riboflavin instillation, there was a statistically significant decrease of CCT by 6.2% from 475 +/- 40 MUm (range: 535-420 MUm) to 446 +/- 31 MUm (range: 508-400) (P < 0.005). There was no other statistically significant change of CCT during UVA irradiation. Conclusions. A significant decrease of corneal thickness was demonstrated during the isotonic riboflavin with HPMC application while there was no significant change during the pulsed accelerated UVA irradiation. PMID- 26885379 TI - Outcomes of 23-Gauge Vitrectomy Combined with Phacoemulsification, Panretinal Photocoagulation, and Trabeculectomy without Use of Anti-VEGF Agents for Neovascular Glaucoma with Vitreous Hemorrhage. AB - Purpose. To evaluate the outcomes of 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti-VEGF-agents for NVG. Methods. Eighteen eyes of 18 patients with NVG underwent 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti VEGF agents. The preoperative BCVA ranged from light perception to 0.2. The preoperative IOP ranged from 38 mmHg to 64 mmHg with a mean of 54 +/- 8 mmHg. The average follow-up time was 14.5 +/- 3 months with a range from 11 to 24 months. Results. The postoperative VA increased in 14 eyes and was stable in 4 eyes at the final follow-up. The mean IOP was 12 +/- 3 mmHg at postoperative day 1. The mean IOP was 15 +/- 2 mmHg, 16 +/- 3 mmHg, 23 +/- 5 mmHg, 28 +/- 4 mmHg, 22 +/- 5 mmHg, 17 +/- 3 mmHg, and 19 +/- 4 mmHg at postoperative days 2 and 3, 1, 2, 3, and 12 weeks, and 1 year postoperatively, respectively, with a range from 10 to 30 mmHg at the final follow-up time point of one year. The IOP was significantly lower than the preoperative one 12 weeks postoperatively (p < 0.05). Conclusion. 23-gauge vitrectomy combined with phacoemulsification, PRP, and trabeculectomy without use of anti-VEGF-agents is a safe and effective method in treating NVG. PMID- 26885375 TI - Effectiveness of regular weighing, weight target setting and feedback by community midwives within routine antenatal care in preventing excessive gestational weight gain: randomised controlled trial. AB - BACKGROUND: Many pregnant women gain excess weight during pregnancy which increases the health risks to the mother and her baby. Interventions to prevent excess weight gain need to be given to the whole population to prevent excess weight gain. The aim of this study was to assess the effectiveness of a simple and brief intervention embedded withinroutine antenatal care to prevent excessive gestation weight gain. METHODS: Six hundred and ten pregnant women (between 10-14 weeks gestation), aged >=18 years with a body mass index (BMI) >=18.5 kg/m2, planned to receive community midwife led care or shared care at the time of recruitment are eligible to take part in the study. Women will be recruited from four maternity centres in England. Community midwives complete a short training module before delivering the intervention. In the intervention, midwives weigh women, set maximum weight limits for weight gain at each antenatal appointment and ask women to monitor their weight at home. Themaximum weight limit is adjusted by the midwife at each antenatal appointment if women have exceeded their maximum weight gain limit set at their previous appointment. The intervention will be compared with usual antenatal care. The primary outcome is the proportion of women per group who exceed the Institute of Medicine guidelines for gestational weight gain at 38 weeks of pregnancy according to their early pregnancy BMI category. DISCUSSION: The proposed trial will test a brief intervention comprising regular weighing, target setting and monitoring ofweight during pregnancy that can be delivered at scale as part of routine antenatal care. Using the professional expertise of community midwives, but without specialist training in weight management, the intervention will incur minimal additionalhealthcare costs, and if effective at reducing excess weight gain, is likely to be very cost effective. TRIAL REGISTRATION: Current controlled trials ISRCTN67427351. Date assigned 29/10/2014. PMID- 26885380 TI - Zeaxanthin: Review of Toxicological Data and Acceptable Daily Intake. AB - Zeaxanthin is a nutritional carotenoid with a considerable amount of safety data based on regulatory studies, which form the basis of its safety evaluation. Subchronic OECD guideline studies with mice and rats receiving beadlet formulations of high purity synthetic zeaxanthin in the diet at dosages up to 1000 mg/kg body weight (bw)/day, and in dogs at over 400 mg/kg bw/day, produced no adverse effects or histopathological changes. In developmental toxicity studies, there was no evidence of fetal toxicity or teratogenicity in rats or rabbits at dosages up to 1000 or 400 mg/kg bw/day, respectively. Formulated zeaxanthin was not mutagenic or clastogenic in a series of in vitro and in vivo tests for genotoxicity. A 52-week chronic oral study in Cynomolgus monkeys at doses of 0.2 and 20 mg/kg bw/day, mainly designed to assess accumulation and effects in primate eyes, showed no adverse effects. In a rat two-generation study, the NOAEL was 150 mg/kg bw/day. In 2012, this dosage was used by EFSA (NDA Panel), in association with a 200-fold safety factor, to propose an Acceptable Daily Intake equivalent to 53 mg/day for a 70 kg adult. The requested use level of 2 mg/day was ratified by the EU Commission. PMID- 26885382 TI - Visual and Refractive Outcomes of a Toric Presbyopia-Correcting Intraocular Lens. AB - Purpose. To evaluate outcomes in astigmatic patients implanted with the Trulign (Bausch + Lomb) toric presbyopia-correcting intraocular lens (IOL) during cataract surgery in a clinical practice setting. Methods. Retrospective study in 40 eyes (31 patients) that underwent cataract extraction and IOL implantation in a procedure using intraoperative wavefront aberrometry guidance (ORA system). Endpoints included uncorrected visual acuity (VA), reduction in refractive cylinder, accuracy to target, axis orientation, and safety. Results. At postoperative month 1, refractive cylinder was <=0.50 D in 97.5% of eyes (<=1.00 D in 100%), uncorrected distance VA was 20/25 or better in 95%, uncorrected intermediate VA was 20/25 or better in 95%, and uncorrected near VA was 20/40 (J3 equivalent) or better in 92.5%. Manifest refraction spherical equivalent was within 1.00 D of target in 95% of eyes and within 0.50 D in 82.5%. Lens rotation was <5 degrees and best-corrected VA was 20/25 or better in all eyes. Conclusion. The IOL effectively reduced refractive cylinder and provided excellent uncorrected distance and intermediate vision and functional near vision. Refractive predictability and rotational stability were exceptional. Implantation of this toric presbyopia-correcting IOL using ORA intraoperative aberrometry provides excellent refractive and visual outcomes in a standard of care setting. PMID- 26885381 TI - Comparison of Two Botulinum Neurotoxin A Injection Patterns with or without the Medial Lower Eyelid in the Treatment of Blepharospasm. AB - The aim of this study was to evaluate the efficacy of two botulinum toxin A (BoNT A) injection patterns with or without the medial lower eyelid (MLE) in treating benign essential blepharospasm (BEB) and influencing lacrimal drainage. Two different injection patterns of BoNT-A were randomly applied to 98 eyes of 49 BEB patients: MLE Group received a full injection pattern of 5 sites and non-MLE Group received a MLE waived injection pattern of 4 sites. Tear breakup time (BUT), Schirmer I test, lagophthalmos height, and lower lid tear meniscus height (TMH) were measured and Jankovic Rating Scale (JRS) was surveyed before injection and at 1 week, 1 month, and 3 months after injection. The symptom of BEB was relieved in both groups as suggested by JRS scores at all time points after injection, and MLE Group came up with a better JRS score at 3 months. The increases of Schirmer I test value and TMH in MLE Group were higher than those in non-MLE Group at 1 week after injection. This study shows that the MLE-involved full injection pattern is a better choice for patients with BEB. It has longer lasting effects in relieving BEB symptoms and better efficacy in reducing lacrimal drainage. Clinical Trials registration number is NCT02327728. PMID- 26885383 TI - Risk Factors and Adverse Events Poorly Predict Infections and Hypogammaglobulinemia in Granulomatosis with Polyangiitis Patients Receiving Rituximab. AB - Background. 29 GPA patients from the Northern Norway vasculitis disease registry received rituximab (RTX) induction and maintenance. 24% and 31% had, respectively, severe and chronic infections while 45% had hypogammaglobulinemia and 28% discontinued RTX due to hypogammaglobulinemia. The aim of the study was to examine how known predictors and adverse events interacted with adverse events using structural statistical methods. Methods. Five predictors (age, cyclophosphamide, total Ig and CD4/CD8 ratio prior RTX, and type of RTX maintenance regimen) and 4 adverse events (severe and chronic infections, hypogammaglobulinemia, and RTX discontinuation) were modeled in principal component and redundancy analyses. Results. The 5 predictors explained 51% of the variance of the GPA cohort. Models including cyclophosphamide exposure and total Ig level predicted best adverse events. However total Ig level has low R squared. The 2 best combinations of adverse events explained 13% of the variance of the predictors and adverse events. Only chronic infections were associated with combination of all adverse events (P = 0.014). Hypogammaglobulinemia did not seem associated with the other adverse events. Conclusions. Traditional risk factors for infections and hypogammaglobulinemia seemed to poorly predict adverse events in our GPA cohort. PMID- 26885384 TI - Clinical Manifestations Associated with Overweight/Obesity in Puerto Ricans with Fibromyalgia Syndrome. AB - Objective. To determine the clinical manifestations associated with overweight/obesity in Hispanics from Puerto Rico with fibromyalgia syndrome (FMS). Methods. A cross-sectional study was performed in 144 patients with FMS (per American College of Rheumatology (ACR) classification criteria). Sociodemographic features, FMS-related symptoms, tender points (per ACR criteria), comorbidities, and FMS treatment were examined. BMI was calculated and patients were grouped into two categories: BMI <= 24.9 kg/m(2) (nonoverweight/obese) and BMI >= 25 kg/m(2) (overweight/obese). Bivariate and multivariate analyses were used to evaluate differences between the study groups. Results. The mean (standard deviation (SD)) age of patients was 50.2 (9.9) years; 95.1% were females and 75.7% were overweight/obese. In the bivariate analysis, overweight/obese patients were more likely to have self-reported memory impairment, anxiety, shortness of breath, and urinary frequency than nonoverweight/obese patients. In addition, the tender point count was higher in the overweight/obese group. In the logistic regression analyses, self-reported memory impairment and urinary frequency differences remained significant after adjusting for confounding variables. Conclusion. In this population of Puerto Ricans with FMS, overweight/obese patients experienced more FMS-related manifestations than nonoverweight/obese individuals. However, prospective studies are needed to confirm these associations and to elucidate if weight reduction interventions could favorably impact the severity of FMS. PMID- 26885386 TI - Breakfast Protein Source Does Not Influence Postprandial Appetite Response and Food Intake in Normal Weight and Overweight Young Women. AB - Breakfasts higher in protein lead to a greater reduction in hunger compared to breakfasts higher in carbohydrate. However, few studies have examined the impact of higher protein breakfasts with differing protein sources. Our objective was to determine if protein source (animal protein (AP) versus plant protein (PP)) influences postprandial metabolic response in participants consuming a high protein breakfast (~30% energy from protein). Normal weight (NW; n = 12) and overweight women (OW; n = 8) aging 18-36 were recruited to participate. Participants completed two visits in a randomized, cross-over design with one week between visits. Subjects had 15 minutes to consume each breakfast. Blood glucose and appetite were assessed at baseline, 15, 30, 45, 60, and 120 minutes postprandial. Participants kept a 24-hour dietary record for the duration of each test day. No difference was found between NW and OW participants or breakfasts for postprandial appetite responses. AP had a significantly lower glucose response at 30 minutes compared with PP (-11.6%; 127 +/- 4 versus 112 +/- 4 mg/dL; P < 0.05) and a slower return to baseline. There was no difference in daily energy intake between breakfasts. These data suggest that protein source may influence postprandial glucose response without significantly impacting appetite response in breakfast consumers. PMID- 26885385 TI - Obesity Severity, Dietary Behaviors, and Lifestyle Risks Vary by Race/Ethnicity and Age in a Northern California Cohort of Children with Obesity. AB - Identification of modifiable behaviors is important for pediatric weight management and obesity prevention programs. This study examined obesogenic behaviors in children with obesity in a Northern California obesity intervention program using data from a parent/teen-completed intake questionnaire covering dietary and lifestyle behaviors (frequency of breakfast, family meals, unhealthy snacking and beverages, fruit/vegetable intake, sleep, screen time, and exercise). Among 7956 children with BMI >= 95th percentile, 45.5% were females and 14.2% were 3-5, 44.2% were 6-11, and 41.6% were 12-17 years old. One-quarter (24.9%) were non-Hispanic white, 11.3% were black, 43.5% were Hispanic, and 12.0% were Asian/Pacific Islander. Severe obesity was prevalent (37.4%), especially among blacks, Hispanics, and older children, and was associated with less frequent breakfast and exercise and excess screen time, and in young children it was associated with consumption of sweetened beverages or juice. Unhealthy dietary behaviors, screen time, limited exercise, and sleep were more prevalent in older children and in selected black, Hispanic, and Asian subgroups, where consumption of sweetened beverages or juice was especially high. Overall, obesity severity and obesogenic behaviors increased with age and varied by gender and race/ethnicity. We identified several key prevalent modifiable behaviors that can be targeted by healthcare professionals to reduce obesity when counseling children with obesity and their parents. PMID- 26885387 TI - Review and Outcome of Prolonged Cardiopulmonary Resuscitation. AB - The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors. Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 +/- 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 +/- 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients. Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts. PMID- 26885388 TI - Atherosclerosis as Extrahepatic Manifestation of Chronic Infection with Hepatitis C Virus. AB - Chronic hepatitis C virus infection is associated with significant morbidity and mortality, as a result of progression towards advanced natural course stages including cirrhosis and hepatocellular carcinoma. On the other hand, the SVR following successful therapy is generally associated with resolution of liver disease in patients without cirrhosis. Patients with cirrhosis remain at risk of life-threatening complications despite the fact that hepatic fibrosis may regress and the risk of complications such as hepatic failure and portal hypertension is reduced. Furthermore, recent data suggest that the risk of HCC and all-cause mortality is significantly reduced, but not eliminated, in cirrhotic patients who clear HCV compared to untreated patients and nonsustained virological responders. Data derived from studies have demonstrated a strong link between HCV infection and the atherogenic process. Subsequently HCV seems to represent a strong, independent risk factor for coronary heart disease, carotid atherosclerosis, stroke, and, ultimately, CVD related mortality. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus which may influence the life expectancy and the quality of patients' life. PMID- 26885389 TI - Association between Fellowship Training, Surgical Volume, and Laparoscopic Suturing Techniques among Members of the American Association of Gynecologic Laparoscopists. AB - Study Objective. To compare surgical volume and techniques including laparoscopic suturing among members of the American Association of Gynecologic Laparoscopists (AAGL) according to fellowship training status. Design. A web-based survey was designed using Qualtrics and sent to AAGL members. Results. Minimally invasive gynecologic surgery (FMIGS) trained surgeons were more likely to perform more than 8 major conventional laparoscopic cases per month (63% versus 38%, P < 0.001, OR [95% CI] = 2.78 [1.54-5.06]) and were more likely to perform laparoscopic suturing during these cases (32% versus 16%, P < 0.004, OR [95% CI] = 2.44 [1.25-4.71]). The non-fellowship trained (NFT) surgeons in private practice were less likely to perform over 8 conventional laparoscopic cases (34% versus 51%, P = 0.03, OR [95% CI] = 0.50 [0.25-0.99]) and laparoscopic suturing during these cases (13% versus 27%, P = 0.01, OR [95% CI] = 0.39 [0.17-0.92]) compared to NFT surgeons in academic practice. Conclusion. The surgical volume and utilization of laparoscopic suturing of FMIGS trained surgeons are significantly increased compared to NFT surgeons. Academic practice setting had a positive impact on surgical volume of NFT surgeons but not on FMIGS trained surgeons. PMID- 26885390 TI - Factors Related to Postoperative Pain Trajectories following Total Knee Arthroplasty: A Longitudinal Study of Patients Admitted to a Russian Orthopaedic Clinic. AB - This study explores sociodemographic, clinical, and surgical factors in relation to pain trajectories during the first 3 days following total knee arthroplasty (TKA). 100 patients (mean age 63.5 +/- 7.8 years and 93% female) consecutively admitted for uncomplicated primary TKA were prospectively included. Postoperative pain was assessed using pain diaries. Measures of preoperative pain, symptoms, daily functioning, quality of life, comorbidities, knee function, perioperative characteristics, and physical/biochemical parameters were also evaluated. All pain ratings decreased in the three days following surgery (p < .001) as well as the reported number of daily hours in moderate/severe pain (p < .001). Women reported more pain than men (p = .009). Pain trajectories did not differ by education, employment, cohabitation, or any patient clinical and biochemical characteristics but were significantly related to preoperative anxiety (p = .029). Patients reporting moderate/severe pain prior to surgery also reported more hours in moderate/severe pain on days 0-3 postoperatively (p = .029). Patients with surgeries longer than 90 min reported more hours of moderate/severe pain compared with patients who had shorter surgeries (p = .008), and similar results were observed for ratings of pain with activity (p = .012). In this sample, only female gender, higher levels of preoperative pain and anxiety, and longer surgical duration were associated with increased pain after TKA. PMID- 26885392 TI - Differences between Groups of Family Physicians with Different Attitudes towards At-Risk Drinkers: A Post Hoc Study of the ODHIN Survey in Portugal. AB - Introduction. We have recently shown that family physicians can be classified into two groups based on their attitudes towards at-risk drinkers: one with better and the other with worse attitudes. Objective. To compare the two groups regarding demographics, alcohol-related clinical practice, knowledge of sensible drinking limits, and barriers and facilitators to working with at-risk drinkers. Methods. A random sample of 234 Portuguese family physicians who answered the Optimizing Delivery of Health Care Interventions survey was included. The questionnaire asked questions on demographics, alcohol-related clinical practice, knowledge of sensible drinking limits, and barriers and facilitators to working with at-risk drinkers. Results. Family physicians with better attitudes were younger (p = 0.005) and less experienced (p = 0.04) and with higher male proportion (p = 0.01). This group had more hours of postgraduate training (p < 0.001), felt more prepared to counsel risky drinkers (p < 0.001), and considered themselves to have better counselling efficacy (p < 0.001). More family physicians in the group with worse attitudes considered that doctors cannot identify risky drinkers without symptoms (p = 0.01) and believed counselling is difficult (p = 0.005). Conclusions. Family physicians with better attitudes had more education on alcohol and fewer barriers to work with at-risk drinkers. These differences should be taken into account when designing implementation programs seeking to increase alcohol screening and brief advice. PMID- 26885391 TI - Imaging of Hip Pain: From Radiography to Cross-Sectional Imaging Techniques. AB - Hip pain can have multiple causes, including intra-articular, juxta-articular, and referred pain, mainly from spine or sacroiliac joints. In this review, we discuss the causes of intra-articular hip pain from childhood to adulthood and the role of the appropriate imaging techniques according to clinical suspicion and age of the patient. Stress is put on the findings of radiographs, currently considered the first imaging technique, not only in older people with degenerative disease but also in young people without osteoarthritis. In this case plain radiography allows categorization of the hip as normal or dysplastic or with impingement signs, pincer, cam, or a combination of both. PMID- 26885393 TI - Fabrication and Optimization of ChE/ChO/HRP-AuNPs/c-MWCNTs Based Silver Electrode for Determining Total Cholesterol in Serum. AB - The developed method used three enzymes comprised of cholesterol esterase, cholesterol oxidase, and peroxidase for fabrication of amperometric biosensor in order to determine total cholesterol in serum samples. Gold nanoparticles (AuNPs) and carboxylated multiwall carbon nanotubes (cMWCNTs) were used to design core of working electrode, having covalently immobilized ChO, ChE, and HRP. Polyacrylamide layer was finally coated on working electrode in order to prevent enzyme leaching. Chemically synthesised Au nanoparticles were subjected to transmission electron microscopy (TEM) for analysing the shape and size of the particles. Working electrode was subjected to FTIR and XRD. The combined action of AuNP and c-MWCNT showed enhancement in electrocatalytic activity at a very low potential of 0.27 V. The pH 7, temperature 40 degrees C, and response time of 20 seconds, respectively, were observed. The biosensor shows a broad linear range from 0.5 mg/dL to 250 mg/dL (0.01 mM-5.83 mM) with minimum detection limit being 0.5 mg/dL (0.01 mM). The biosensor showed reusability of more than 45 times and was stable for 60 days. The biosensor was successfully tested for determining total cholesterol in serum samples amperometrically with no significant interference by serum components. PMID- 26885394 TI - Halophilic Bacteria of Lunsu Produce an Array of Industrially Important Enzymes with Salt Tolerant Activity. AB - The halophilic bacterial isolates SS1, SS2, SS3, SS5, and SS8 were characterized for production of industrially important enzymes like amylase, protease, lipase, and glutaminase. Halophilic bacterial isolates SS1 and SS3 exhibited salt dependent extracellular amylase and protease activities. Both the halophilic isolates SS1 and SS3 exhibited maximum amylase and protease activities in the presence of 1.5 and 1.0 M NaCl, respectively, with the optimum pH 8 and temperature 40 degrees C. SS2 showed maximum extracellular protease and lipase activities in the presence of 0.75 M NaCl, at optimum pH of 7, and temperature 37 degrees C. The glutaminase activity of SS3 increased with increase in concentration of NaCl up to 2.5 M. The optimum pH and temperature for L glutaminase activity of SS3 was 8 and 40 degrees C, respectively. The combined hydrolytic activities of these halophilic bacterial isolates can be used for bioconversion of organic materials to useful products. PMID- 26885395 TI - Baird-Pattinson Aetiological Classification and Phases of Delay Contributing to Stillbirths in a Nigerian Tertiary Hospital. AB - PURPOSE: This study aims to identify triggers of stillbirth in the study setting and to make suggestions to reduce the prevalence. METHOD: A three-year retrospective case-control study of stillbirths at Ekiti State University Teaching Hospital. RESULTS: The stillbirth rate was 33 per 1000 births. Based on Baird-Pattinson classification of the primary obstetric causes of stillbirth, adverse intrapartum events, hypertensive diseases, and unexplained intrapartum fetal deaths were topmost causes of stillbirths. In comparison with the controls, other identified predictors of SB were grand multiparity (p = 0.016), delays in seeking medical care and/or in receiving treatment (p = 0.001), wrong initial diagnosis (p = 0.001), inadequate intrapartum monitoring (p = 0.001), and inappropriate clinical management (p = 0.001). CONCLUSION: Stillbirth rate remains high in our setting. Elimination of obstacles to accessing care, effective management of hypertensive disorders in pregnancy, updated health facilities, improved dedication to duty, and retraining of health workers will reduce the prevalence. PMID- 26885397 TI - Restriction Profiling of 23S Microheterogenic Ribosomal Repeats for Detection and Characterizing of E. coli and Their Clonal, Pathogenic, and Phylogroups. AB - Correlating ribosomal microheterogenicity with unique restriction profiles can prove to be an efficacious and cost-effective approach compared with sequencing for microbial identification. An attempt to peruse restriction profiling of 23S ribosomal assemblage was ventured; digestion patterns with Bfa I discriminated E. coli from its colony morphovars, while Hae III profiles assisted in establishing distinct clonal groups. Among the gene pool of 399 ribosomal sequences extrapolated from 57 E. coli genomes, varying degree of predominance (I > III > IV > II) of Hae III pattern was observed. This was also corroborated in samples collected from clinical, commensal, and environmental origin. K-12 and its descendants showed type I pattern whereas E. coli-B and its descendants exhibited type IV, both of these patterns being exclusively present in E. coli. A near possible association between phylogroups and Hae III profiles with presumable correlation between the clonal groups and different pathovars was established. The generic nature, conservation, and barcode gap of 23S rRNA gene make it an ideal choice and substitute to 16S rRNA gene, the most preferred region for molecular diagnostics in bacteria. PMID- 26885398 TI - Association of RBP4 Genotype with Phenotypic Reproductive Traits of Sows. AB - PCR-RFLP was applied to a commercial crossbred pig population in order to investigate the association between polymorphism (SNP) of Retinol-binding protein 4 (RBP4) gene and reproductive performance. 400 sows were genotyped and 2000 records of reproductive traits were used in order to retrieve information about the allele frequencies and the association of the RBP4 gene with main reproductive characteristics of the population. A deviation from the Hardy Weinberg equilibrium was observed as a result of the AB genotype excess. In addition, the AA genotype saw statistically significant higher values of (i) the total number of born piglets (p < 0.05), (ii) the number of piglets born alive (p < 0.01), and (iii) the number of weaned piglets (p < 0.01). The number of the mummified piglets and the number of the piglets born dead did not differ between the various RBP4 genotypes. Interestingly, the AA genotype had a negative impact (p < 0.05) on the number of piglets born dead, resulting indirectly in a larger litter size. In conclusion, the AA genotype and in extension the A allele of RBP4 gene are in favor of producing larger litter size, suggesting that the RBP4 gene may be used in Marker-Assisted Selection (MAS) programs for a rapid improvement of the reproductive characteristics in pigs. PMID- 26885399 TI - Poor Sleep in Multiple Sclerosis Correlates with Beck Depression Inventory Values, but Not with Polysomnographic Data. AB - Objectives. Pittsburgh Sleep Quality Index (PSQI) values correlate with depression, but studies investigating the relationship between PSQI values and polysomnographic (PSG) data showed inconsistent findings. Methods. Sixty-five consecutive patients with multiple sclerosis (MS) were retrospectively classified as "good sleepers" (GS) (PSQI <= 5) and "poor sleepers" (PS) (PSQI > 5). The PSG data and the values of the Visual Analog Scale (VAS) of fatigue, Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), and the Beck Depression Inventory (BDI) were compared. Results. No significant differences were found either for PSG data or for ESS, MFIS, and FSS values; but PS showed significantly increased BDI and VAS values. Conclusions. Poor sleep is associated with increased depression and fatigue scale values. PMID- 26885396 TI - Beliefs, Barriers, and Preferences of European Overweight Women to Adopt a Healthier Lifestyle in Pregnancy to Minimize Risk of Developing Gestational Diabetes Mellitus: An Explorative Study. AB - INTRODUCTION: We explored beliefs, perceived barriers, and preferences regarding lifestyle changes among overweight European pregnant women to help inform the development of future lifestyle interventions in the prevention of gestational diabetes mellitus. METHODS: An explorative mixed methods, two-staged study was conducted to gather information from pregnant European women (BMI >= 25 kg/m2). In three European countries 21 interviews were conducted, followed by 71 questionnaires in six other European countries. Content analysis and descriptive and chi-square statistics were applied (p < 0.05). RESULTS: Women preferred to obtain detailed information about their personal risk. The health of their baby was a major motivating factor. Perceived barriers for physical activity included pregnancy-specific issues such as tiredness and experiencing physical complaints. Insufficient time was a barrier more frequently reported by women with children. Abstaining from snacking was identified as a challenge for the majority of women, especially for those without children. Women preferred to obtain support from their partner, as well as health professionals and valued flexible lifestyle programs. CONCLUSIONS: Healthcare professionals need to inform overweight pregnant women about their personal risk, discuss lifestyle modification, and assist in weight management. Lifestyle programs should be tailored to the individual, taking into account barriers experienced by overweight first-time mothers and multipara women. PMID- 26885401 TI - Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease. AB - Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1-/- mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1-/- mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1-/- mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia. PMID- 26885400 TI - Eyes Open on Sleep and Wake: In Vivo to In Silico Neural Networks. AB - Functional and effective connectivity of cortical areas are essential for normal brain function under different behavioral states. Appropriate cortical activity during sleep and wakefulness is ensured by the balanced activity of excitatory and inhibitory circuits. Ultimately, fast, millisecond cortical rhythmic oscillations shape cortical function in time and space. On a much longer time scale, brain function also depends on prior sleep-wake history and circadian processes. However, much remains to be established on how the brain operates at the neuronal level in humans during sleep and wakefulness. A key limitation of human neuroscience is the difficulty in isolating neuronal excitation/inhibition drive in vivo. Therefore, computational models are noninvasive approaches of choice to indirectly access hidden neuronal states. In this review, we present a physiologically driven in silico approach, Dynamic Causal Modelling (DCM), as a means to comprehend brain function under different experimental paradigms. Importantly, DCM has allowed for the understanding of how brain dynamics underscore brain plasticity, cognition, and different states of consciousness. In a broader perspective, noninvasive computational approaches, such as DCM, may help to puzzle out the spatial and temporal dynamics of human brain function at different behavioural states. PMID- 26885402 TI - Linking Mitochondria to Synapses: New Insights for Stress-Related Neuropsychiatric Disorders. AB - The brain evolved cellular mechanisms for adapting synaptic function to energy supply. This is particularly evident when homeostasis is challenged by stress. Signaling loops between the mitochondria and synapses scale neuronal connectivity with bioenergetics capacity. A biphasic "inverted U shape" response to the stress hormone glucocorticoids is demonstrated in mitochondria and at synapses, modulating neural plasticity and physiological responses. Low dose enhances neurotransmission, synaptic growth, mitochondrial functions, learning, and memory whereas chronic, higher doses produce inhibition of these functions. The range of physiological effects by stress and glucocorticoid depends on the dose, duration, and context at exposure. These criteria are met by neuronal activity and the circadian, stress-sensitive and ultradian, stress-insensitive modes of glucocorticoid secretion. A major hallmark of stress-related neuropsychiatric disorders is the disrupted glucocorticoid rhythms and tissue resistance to signaling with the glucocorticoid receptor (GR). GR resistance could result from the loss of context-dependent glucocorticoid signaling mediated by the downregulation of the activity-dependent neurotrophin BDNF. The coincidence of BDNF and GR signaling changes glucocorticoid signaling output with consequences on mitochondrial respiration efficiency, synaptic plasticity, and adaptive trajectories. PMID- 26885403 TI - Gender Differences in the Neurobiology of Anxiety: Focus on Adult Hippocampal Neurogenesis. AB - Although the literature reports a higher incidence of anxiety disorders in women, the majority of basic research has focused on male rodents, thus resulting in a lack of knowledge on the neurobiology of anxiety in females. Bridging this gap is crucial for the design of effective translational interventions in women. One of the key brain mechanisms likely to regulate anxious behavior is adult hippocampal neurogenesis (AHN). This review paper aims to discuss the evidence on the differences between male and female rodents with regard to anxiety-related behavior and physiology, with a special focus on AHN. The differences between male and female physiologies are greatly influenced by hormonal differences. Gonadal hormones and their fluctuations during the estrous cycle have often been identified as agents responsible for sexual dimorphism in behavior and AHN. During sexual maturity, hormone levels fluctuate cyclically in females more than in males, increasing the stress response and the susceptibility to anxiety. It is therefore of great importance that future research investigates anxiety and other neurophysiological aspects in the female model, so that results can be more accurately applicable to the female population. PMID- 26885406 TI - Background Noise Contributes to Organic Solvent Induced Brain Dysfunction. AB - Occupational exposure to complex blends of organic solvents is believed to alter brain functions among workers. However, work environments that contain organic solvents are also polluted with background noise which raises the issue of whether or not the noise contributed to brain alterations. The purpose of the current study was to determine whether or not repeated exposure to low intensity noise with and without exposure to a complex blend of organic solvents would alter brain activity. Female Fischer344 rats served as subjects in these experiments. Asynchronous volume conductance between the midbrain and cortex was evaluated with a slow vertex recording technique. Subtoxic solvent exposure, by itself, had no statistically significant effects. However, background noise significantly suppressed brain activity and this suppression was exacerbated with solvent exposure. Furthermore, combined exposure produced significantly slow neurotransmission. These abnormal neurophysiologic findings occurred in the absence of hearing loss and detectable damage to sensory cells. The observations from the current experiment raise concern for all occupations where workers are repeatedly exposed to background noise or noise combined with organic solvents. Noise levels and solvent concentrations that are currently considered safe may not actually be safe and existing safety regulations have failed to recognize the neurotoxic potential of combined exposures. PMID- 26885405 TI - The Right Hemisphere Planum Temporale Supports Enhanced Visual Motion Detection Ability in Deaf People: Evidence from Cortical Thickness. AB - After sensory loss, the deprived cortex can reorganize to process information from the remaining modalities, a phenomenon known as cross-modal reorganization. In blind people this cross-modal processing supports compensatory behavioural enhancements in the nondeprived modalities. Deaf people also show some compensatory visual enhancements, but a direct relationship between these abilities and cross-modally reorganized auditory cortex has only been established in an animal model, the congenitally deaf cat, and not in humans. Using T1 weighted magnetic resonance imaging, we measured cortical thickness in the planum temporale, Heschl's gyrus and sulcus, the middle temporal area MT+, and the calcarine sulcus, in early-deaf persons. We tested for a correlation between this measure and visual motion detection thresholds, a visual function where deaf people show enhancements as compared to hearing. We found that the cortical thickness of a region in the right hemisphere planum temporale, typically an auditory region, was greater in deaf individuals with better visual motion detection thresholds. This same region has previously been implicated in functional imaging studies as important for functional reorganization. The structure-behaviour correlation observed here demonstrates this area's involvement in compensatory vision and indicates an anatomical correlate, increased cortical thickness, of cross-modal plasticity. PMID- 26885404 TI - Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation. AB - TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. PMID- 26885409 TI - Anaesthetic Management of a Patient with Thyrotoxicosis for Nonthyroid Surgery with Peripheral Nerve Blockade. AB - Thyrotoxicosis is a hypermetabolic condition caused by an elevation in thyroid hormone levels. The disorder has a variety of causes, manifestations, and therapies. Several clinical features of thyrotoxicosis are due to sympathetic stimulation with increased beta-adrenoreceptor upregulation and sensitization to catecholamine. Anaesthetic management of thyrotoxicosis patients using neuraxial block has been described in literature; however, to our knowledge, there are no reports of peripheral nerve block utilization. Here, we report on the anaesthetic management of a patient with thyroiditis-associated thyrotoxicosis undergoing emergency surgery via a femoral and sciatic nerve block. PMID- 26885410 TI - Anomalous Origination of Right Coronary Artery from Left Sinus in Asymptomatic Young Male Presenting with Positive Ischemic Response on Treadmill Test. AB - Anomalous origination of coronary artery from the opposite sinus (ACAOS) is a rare coronary artery anomaly. Right ACAOS with interarterial course is a type of ACAOS, which conveys a high risk for myocardial ischemia or sudden death. We reported a case of right ACAOS with interarterial course in otherwise healthy young male. He was asymptomatic, until an obligatory medical check-up with treadmill test showed a sign of positive ischemic response. Further work-up revealed that he had right ACAOS with interarterial course. Watchful observation was applied to him, while strenuous physical activity and competitive sport were absolutely prohibited. PMID- 26885407 TI - Inhibition Plasticity in Older Adults: Practice and Transfer Effects Using a Multiple Task Approach. AB - OBJECTIVE. To examine plasticity of inhibition, as indexed by practice effects of inhibition tasks and the associated transfer effects, using a multiple task approach in healthy older adults. METHOD. Forty-eight healthy older adults were evenly assigned to either a practice group or a no-contact control group. All participants completed pretest (2.5 hours) and posttest (2 hours) sessions, with a 2-week interval in between. During the 2-week interval, only the practice group completed six 30-minute practice sessions (three sessions per week for two consecutive weeks) of three lab-based inhibition tasks. RESULTS. All three inhibition tasks demonstrated significant improvement across practice sessions, suggesting practice-induced plasticity. The benefit, however, only transferred to near-near tasks. The results are inconclusive with regard to the near-far and far far transfer effects. DISCUSSION. This study further extends literature on practice effects of inhibition in older adults by using a multiple task approach. Together with previous work, the current study suggests that older adults are able to improve inhibition performance through practice and transfer the practice gains to tasks that overlap in both target cognitive ability and task structure (i.e., near-near tasks). PMID- 26885408 TI - Functional Integration between Salience and Central Executive Networks: A Role for Action Video Game Experience. AB - Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts' and amateurs' resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity. PMID- 26885411 TI - Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure. AB - A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed. PMID- 26885412 TI - Misdiagnosis of Extensive Maxillofacial Infection and Its Relationship with Periodontal Problems and Hyperglycemia. AB - Background. Complex dental infections can reach distant areas of the alveolar process, invading the secondary fascial spaces. Objectives. This case report aims to show a misdiagnosis of odontogenic infection and a great need for dentist in the hospital environment. Case Report. A male patient presented facial asymmetry and trismus, while the facial CT examination showed a hyperdense mass involving the left masseteric, pterygomandibular, and superficial temporal regions. The patient was then referred to oral oncology center by emergency physician with cancer suspicion. After 15 days, the patient returned to the same emergency room and was attended by the surgical and maxillofacial trauma team, presenting tachycardia, tachypnea, dysphagia, and trismus. During anamnesis, the patient reported being an uncontrolled diabetic. In intraoral exam, a poor oral condition and generalized periodontitis were observed. Results. Correct diagnosis of odontogenic infection was established and adequately treated. Conclusions. Symptomatology bland may mask the severity of an infection; every increase in volume associated with trismus, poor oral hygiene with or without hyperglycemia should be heavily investigated for the presence of an infectious process. It emphasizes the importance of a dentist working with the physician in emergency room. PMID- 26885413 TI - Gingival Overgrowth Leading to the Diagnosis of Familial Tuberous Sclerosis Complex. AB - Tuberous sclerosis complex (TSC), a neurocutaneous syndrome, is characterized by the development of benign tumours affecting different body systems. We herein present a report of a 40-year-old female patient presenting with dental enamel pits and localized gingival overgrowth that eventually lead to the diagnosis of a case of familial TSC. Diagnosis of familial TSC by comprehensive oral examination and detection of oral manifestations proved to be inevitable as it resulted in institution of appropriate treatment strategies and genetic counselling of the affected family. PMID- 26885414 TI - A Novel Nonsense Mutation of the AGL Gene in a Romanian Patient with Glycogen Storage Disease Type IIIa. AB - Background. Glycogen storage disease type III (GSDIII) is a rare metabolic disorder with autosomal recessive inheritance, caused by deficiency of the glycogen debranching enzyme. There is a high phenotypic variability due to different mutations in the AGL gene. Methods and Results. We describe a 2.3-year old boy from a nonconsanguineous Romanian family, who presented with severe hepatomegaly with fibrosis, mild muscle weakness, cardiomyopathy, ketotic fasting hypoglycemia, increased transaminases, creatine phosphokinase, and combined hyperlipoproteinemia. GSD type IIIa was suspected. Accordingly, genomic DNA of the index patient was analyzed by next generation sequencing of the AGL gene. For confirmation of the two mutations found, genetic analysis of the parents and grandparents was also performed. The patient was compound heterozygous for the novel mutation c.3235C>T, p.Gln1079(*) (exon 24) and the known mutation c.1589C>G, p.Ser530(*) (exon 12). c.3235 >T, p.Gln1079(*) was inherited from the father, who inherited it from his mother. c.1589C>G, p.Ser530(*) was inherited from the mother, who inherited it from her father. Conclusion. We report the first genetically confirmed case of a Romanian patient with GSDIIIa. We detected a compound heterozygous genotype with a novel mutation, in the context of a severe hepatopathy and an early onset of cardiomyopathy. PMID- 26885415 TI - Massive Retroperitoneal Hemorrhage as an Initial Presentation of a Rare and Aggressive Form of Multiple Myeloma. AB - Multiple myeloma, a plasma cell neoplasm, presents most commonly with anemia, hypercalcemia, renal failure, and bone pain. Only few cases of clinical aggressive presentation associated with bleeding were reported in the medical literature. The reported cases included gastrointestinal bleeding and cardiac tamponade. Spontaneous retroperitoneal haemorrhage as initial presentation has not been so far reported. We hereby report a case of a 64-year-old female who was found to have catastrophic hemorrhage in the retroperitoneal region that extended into intrathecal space causing cord compression. The case posed a significant diagnostic and management dilemma. This case emphasizes the need to think broadly and include multiple myeloma in the diagnosis of unexplained massive retroperitoneal bleeding. PMID- 26885416 TI - Primary Myelofibrosis Presenting as Extramedullary Hematopoiesis in a Transplanted Liver Graft: Case Report and Review of the Literature. AB - Primary myelofibrosis (PMF) commonly results in extramedullary hematopoiesis (EMH) in the spleen and liver as well as a variety of other organs. We present a first report of a unique presentation of PMF in a liver transplant recipient patient as EMH in the transplanted liver graft. A 76-year-old man with history of cryptogenic cirrhosis received cadaveric liver transplantation in 1996. He maintained a normal graft function and stable hematologic parameters until 2013 when he presented with anemia and progressive fatigue. Extensive work-up did not identify the etiology of the recent decline in his hemoglobin; thus a liver biopsy was done which showed findings of EMH within the sinusoids with increased megakaryocytes, some with atypical morphology. A BM biopsy revealed a hypercellular marrow, moderately increased reticulin fibrosis, and features consistent with primary myelofibrosis. Abdominal imaging showed a normal-size spleen and did not identify any sites of EMH outside of the liver. The diagnosis of myelofibrosis was thus made, and this case demonstrated predominant tropism to a transplanted liver graft with absence of EMH elsewhere. We would thus like to emphasize that findings of EMH in subjects with no preexisting hematologic neoplasm should warrant close follow-up and assessment. PMID- 26885417 TI - Another Report of Acalculous Cholecystitis in a Greek Patient with Infectious Mononucleosis: A Matter of Luck or Genetic Predisposition? AB - We here report a case of a young, male patient who presented with jaundice and was diagnosed with acalculous cholecystitis during the course of a primary Epstein-Barr Virus (EBV) infection. The coexistence of cholestatic hepatitis and acalculous cholecystitis in patients with infectious mononucleosis is extremely uncommon and only few cases can be found in the literature. Moreover, almost one fourth of the total reports of this rare entity are coming from Greece. Whether this is a result of physicians' high index of suspicion due to previous reports or a consequence of genetic predisposition is an issue that deserves further investigation in the future. More studies are required in order to clarify the pathophysiological and genetic backgrounds that connect acalculous cholecystitis and EBV infection. PMID- 26885418 TI - Edwardsiella tarda Endocarditis Confirmed by Indium-111 White Blood Cell Scan: An Unusual Pathogen and Diagnostic Modality. AB - Edwardsiella tarda is a freshwater marine member of the family Enterobacteriaceae which often colonizes fish, lizards, snakes, and turtles but is an infrequent human pathogen. Indium-111- ((111)In-) labeled white blood cell (WBC) scintigraphy is an imaging modality which has a wide range of reported sensitivity and specificity (from 60 to 100% and from 68 to 92%, resp.) for diagnosing acute and chronic infection. We describe a case of suspected E. tarda prosthetic aortic valve and mitral valve endocarditis with probable vegetations and new mitral regurgitation on transthoracic and transesophageal echocardiograms which was supported with the use of (111)In-labeled WBC scintigraphy. PMID- 26885419 TI - First Pediatric Case of Tularemia after a Coyote Bite. AB - Bite-transmitted tularemia is a rare event in humans and most of the cases have been associated with cat bites. We report the first pediatric case of tularemia caused by a coyote (Canis latrans) bite. Coyotes can be healthy carriers of Francisella tularensis and transmit this infectious agent through a bite. Pediatricians should be aware of this risk after a carnivore bite and implement appropriate antibiotic therapy, as amoxicillin/clavulanate potassium (Augmentin) may have prolonged the typical two to three days' incubation period commonly observed for tularemia after an animal bite and was not effective in preventing clinical signs in this child. Finally, it emphasizes again the importance of early and late serum samples for appropriate serodiagnostic. PMID- 26885420 TI - Clival Ectopic Pituitary Adenoma Mimicking a Chordoma: Case Report and Review of the Literature. AB - Background. Purely ectopic pituitary adenomas are exceedingly rare. Here we report on a patient that presented with an incidental clival mass thought to be a chordoma. Endonasal resection, tumor pathology, and endocrinology workup revealed a prolactinoma. Case Presentation. A 41-year-old male presented with an incidental clival lesion presumed to be a chordoma. On MRI it involved the entire clivus, extended laterally to the petroclival junction, and invaded the cavernous sinuses bilaterally, encasing both internal carotid arteries, without direct extension into the sella. Intraoperatively, it was clear that the tumor originated from the clivus and that the sellar dura was completely intact. Frozen section pathology was consistent with a pituitary adenoma. Immunostaining was positive for synaptophysin and prolactin with a low Ki-67 index, suggestive of a prolactinoma. Additional immunohistochemical stains seen in chordomas (EMA, S100, and Brachyury) and other metastatic tumors were negative. A postoperative endocrine workup revealed an elevated serum prolactin of 881.3 ng/mL (normal < 20). Conclusions. In conclusion, it is crucial to maintain an extensive differential diagnosis when evaluating a patient with a clival lesion. Ectopic clival pituitary adenomas, although rare, may warrant an endocrinological workup preoperatively as the majority may respond to medical treatment. PMID- 26885421 TI - Bilaterally Symmetrical Lower Extremity Compartment Syndrome following Massive Transfusion. AB - Compartment syndrome is a serious condition characterized by raised intracompartmental pressure, which develops following trauma. Well leg compartment syndrome (WLCS) is a term reserved for compartment syndrome in a nontraumatic setting, usually resulting from prolonged lithotomy position during surgery. In literature, 8 cases have been reported regarding well leg compartment syndrome in a supine position and bilateral symmetrical involvement was observed in only 2 cases. In WLCS etiology, lengthy surgery, lengthy hypotension, and extremity malpositioning have been held responsible but one of the factors with a role in the etiology may have been the tissue oedema and impaired microcirculation formed from the effect of vasoactive mediators expressed into the circulation associated with the massive blood transfusion. The case is presented here regarding symmetrical lower extremity compartment syndrome after surgery in which massive transfusion was made for gross haemorrhage from an abdominal injury. In conclusion, blood transfusion applied at the required time is life-saving but potential risks must always be considered. PMID- 26885422 TI - An Unusual Prepatellar Bursa Swelling: Patellar Button Dissociation and Migration. AB - Implant loosening is not a new phenomenon, nor is implant migration; however they are rarely seen after knee arthroplasty surgery. Complications with patellar buttons have been reported before with peg failure, loosening, and patella fracture; however extra-articular migration is extremely rare. We report an unusual case of patellar button migration 11 years after total knee arthroplasty to the prepatellar bursa. PMID- 26885424 TI - Two Cases of Heerfordt's Syndrome: A Rare Manifestation of Sarcoidosis. AB - Heerfordt's syndrome is a rare manifestation of sarcoidosis characterized by the presence of facial nerve palsy, parotid gland enlargement, anterior uveitis, and low grade fever. Two cases of Heerfordt's syndrome and a literature review are presented. Case 1. A 53-year-old man presented with swelling of his right eyelid, right facial nerve palsy, and swelling of his right parotid gland. A biopsy specimen from the swollen eyelid indicated sarcoidosis and he was diagnosed with incomplete Heerfordt's syndrome based on the absence of uveitis. His symptoms were improved by corticosteroid therapy. Case 2. A 55-year-old woman presented with left facial nerve palsy, bilateral hearing loss, and swelling of her bilateral parotid glands. She had been previously diagnosed with uveitis and bilateral hilar lymphadenopathy. Although no histological confirmation was performed, she was diagnosed with complete Heerfordt's syndrome on the basis of her clinical symptoms. Swelling of the bilateral parotid glands and left facial nerve palsy were improved immediately by corticosteroid therapy. Sarcoidosis is a relatively uncommon disease for the otolaryngologist. However, the otolaryngologist may encounter Heerfordt's syndrome as this syndrome presents with facial nerve palsy and swelling of the parotid gland. Therefore, we otolaryngologists should diagnose and treat Heerfordt's syndrome appropriately in cooperation with pneumologists and ophthalmologists. PMID- 26885423 TI - Management of Femoral Shaft Fracture in Klippel-Trenaunay Syndrome with External Fixator. AB - Klippel-Trenaunay syndrome (KTS) is a rare complex malformation characterized by the clinical triad of capillary malformations, soft tissue and bone hypertrophy, and venous/lymphatic malformation. Fractures of long bones in such cases are challenging to treat. A 12-year-old female with this syndrome presented with femoral shaft fracture of right thigh. She was initially kept on skeletal traction for two weeks and then she underwent closed reduction and immobilization with external fixator with uneventful intraoperative and postoperative period. Fracture united at four and half months. PMID- 26885425 TI - Fibrolipoma of the Buccal Mucosa: A Case Report and Review of the Literature. AB - Lipomas are common benign soft tissue neoplasms derived from mature adipose tissue. However, they rarely arise in the oral cavity. Fibrolipoma is a histological variant of lipoma that mainly affects the buccal mucosa and causes functional and cosmetic issues. This article describes the case of a 71-year-old male with a fibrolipoma of the left buccal mucosa and a review of previous articles about fibrolipoma. PMID- 26885426 TI - Biliary Adenofibroma with Invasive Carcinoma: Case Report and Review of the Literature. AB - We report a case of biliary adenofibroma with an invasive carcinoma in a 71-year old female who presented with bilateral upper abdominal pain. Imaging revealed a 6.3 cm heterogeneously enhancing mass in the left lateral segment of the liver. Histologically, the adenofibroma showed the characteristic components as previously described of biliary adenofibromata, namely, cystic and tubular structures lined by cuboidal to low columnar biliary type epithelium and a dense fibrous stroma composed of spindled cells. Intimately admixed with the adenofibroma was a distinct tumor composed of malignant clear cells which demonstrated stromal and vascular invasion. Although mitotic figures were inconspicuous, Ki67 was brisk and p53 demonstrated 25-50% positivity. Sections also showed a von Meyenberg complex located adjacent to the tumor. This case expands the understanding of this rare tumor and proves two important assertions from previous case reports. First, the presence of an associated von Meyenberg complex with similar morphology and immunohistochemical staining pattern suggests that biliary adenofibromata and von Meyenberg complexes may share related histogenesis. Second, biliary adenofibromata harbor malignant potential and may show malignant transformation. Furthermore, this case highlights the need for these rare tumors to be followed aggressively, as their biological behavior is poorly understood. PMID- 26885427 TI - Tuberculous Dactylitis: An Uncommon Presentation of a Common Infection. AB - Tuberculous dactylitis is an unusual form of osteoarticular tuberculosis involving the short tubular bones of hands and feet, which is uncommon beyond six years of age. We report the case of a fifteen-year-old adolescent boy who was diagnosed with tuberculous dactylitis, involving contralateral hand and foot. His diagnosis was delayed due to lack of suspicion of this rare entity. The report also examines the diagnostic difficulties faced by clinicians in arriving at an appropriate diagnosis. PMID- 26885428 TI - Detection of Myofascial Herniation on Dynamic Sonography and Magnetic Resonance Imaging. AB - Muscle hernia is an uncommon cause of leg swelling. It can be detected in the early stages only if there is a high index of suspicion. It is common in lower extremity compared to the upper extremity. Tibialis anterior muscle in the leg is commonly involved. Dynamic sonography and magnetic resonance imaging (MRI) are the mainstay in their diagnosis, which demonstrate a facial defect with herniation of muscle fibers. We report a case of 23-year-old male patient who presented with a painless swelling in the anterolateral aspect of the left upper leg. Dynamic sonography done with high-resolution probe demonstrated a defect in fascia overlying tibialis anterior with herniation of outer muscle fibers which increased during dorsiflexion and reduced in the supine position at rest. MRI of the left leg confirmed the findings. PMID- 26885430 TI - Infected Abdominal Aortic Aneurysm with Helicobacter cinaedi. AB - Helicobacter cinaedi is a rare human pathogen which has various clinical manifestations such as cellulitis, bacteremia, arthritis, meningitis, and infectious endocarditis. We report an abdominal aortic aneurysm infected with Helicobacter cinaedi, treated successfully with surgical repair and long-term antimicrobial therapy. PMID- 26885429 TI - Pulmonary Disease Secondary to Reflux Mimicking Interstitial Pneumonia in Systemic Sclerosis: Case Report and Literature Review. AB - Systemic sclerosis is a complex disease due to the variety of clinical presentations, often superimposed on other conditions, related or not to the connective tissue. We report a 43-year-old Brazilian woman with limited systemic sclerosis and pulmonary symptoms secondary to gastroesophageal reflux disease, with a clinical presentation similar to a diffuse interstitial lung disease. Because of the frequency of interstitial lung injury due to systemic sclerosis, this was an important differential diagnosis, which could be excluded after optimized treatment of reflux disease, with clinical and radiological improvement. Clinical management of patients with collagen diseases requires clinician skills to identify the natural history and understand its nuances. This is a common situation in clinical practice, but with a few discussions in international literature. PMID- 26885432 TI - Treatment of Cytomegalovirus Infection with Cidofovir and CMV Immune Globulin in a Lung Transplant Recipient. AB - Cytomegalovirus (CMV) infection after lung transplantation is associated with increased risk for pneumonitis and bronchiolitis obliterans as well as allograft rejection and opportunistic infections. Ganciclovir is the mainstay of prophylaxis and treatment but CMV infections can be unresponsive. Apart from direct antiviral drugs, CMV immunoglobulin (CMVIG) preparations may be considered but are only licensed for prophylaxis. A CMV-seronegative 42-year-old man with cystic fibrosis received a lung from a CMV-seropositive donor. Intravenous ganciclovir prophylaxis was delayed until day 12 due to acute postoperative renal failure and was accompanied by five doses of CMVIG (10 g). By day 16, CMV-DNA was detectable and rising; CMV-specific T-cells were undetectable. Switch from ganciclovir to foscarnet prompted a transient decrease in CMV viral load, but after increasing again to reach 3600 copies/mL foscarnet was changed to intravenous cidofovir and CMVIG was restarted. CMV load continued to fluctuate and declined slowly, whereas CMV-specific T-cells were detected five months later and increased thereafter. At last follow-up, the patient was in very good clinical condition with no evidence of bronchiolitis obliterans. No side effects of this treatment were observed. In this hard-to-treat case, the combination of cidofovir with off-label use of CMVIG contributed to a successful outcome. PMID- 26885431 TI - Iatrogenic Spinal Cord Injury during Removal of the Inferior Articular Process in the Presence of Ossification of the Ligamentum Flavum. AB - Ossified ligamentum flavum (OLF) is a condition of heterotopic lamellar bone formation within the yellow ligament. Some patients with OLF can be asymptomatic. However, asymptomatic OLF may not be obvious on preoperative MRI and could increase the risk of iatrogenic injury during treatments for unrelated spinal conditions. This report describes a case of spinal cord injury caused by the indirect transmission of force from an osteotome to an asymptomatic OLF during the resection of a thoracic inferior articular process (IAP). To prevent this outcome, we urge careful review of CT imaging in the preoperative setting and advocate the use of a high-speed drill instead of an osteotome during bone removal in the setting of an adjacent area of OLF. PMID- 26885433 TI - Spontaneous Retroperitoneal Haematoma due to Polyarteritis Nodosa: Report of a Case and Literature Review. AB - Retroperitoneal haematoma is a rare clinical entity with variable etiology. It can happen spontaneously, without any obvious precipitating factors, the so called spontaneous retroperitoneal haematoma. There is no general consensus as to the best management plan for patients with retroperitoneal haematoma. Polyarteritis nodosa (PAN) is a rare cause of retroperitoneal haematoma. Here we report relationship between PAN and retroperitoneal haematoma and treatment approaches. However, an accepted and clearly defined treatment has not been established due to its rarity. PMID- 26885434 TI - High Output Cardiac Failure Resolving after Repair of AV Fistula in a Six-Month Old. AB - Background. Acquired AVF in pediatrics are commonly caused by iatrogenic means, including arterial or venous punctures. These fistulae can cause great hemodynamic stress on the heart as soon as they are created. Case. A six-month old 25-week gestation infant was referred for respiratory distress. Initial exam revealed tachypnea, tachycardia, and hypertension. There was a bruit noted on her left arm. An ultrasound showed an arteriovenous fistula. Its location, however, precluded intervention because of the high risk for limb-loss. An echocardiogram showed evidence of pulmonary hypertension that was treated with sildenafil and furosemide. However, no improvement was seen. On temporary manual occlusion of the fistula, the patient was noted to have increased her blood pressure and decreased her heart rate, suggesting significant hemodynamic effect of the fistula. The fistula was subsequently ligated and the patient clinically and echocardiographically improved. Conclusion. A patient in high output cardiac failure or pulmonary artery hypertension, especially premature patients with preexisting lung disease, should be probed for history of multiple punctures, trauma, or surgery and should have prompt evaluation for AVF. If it can be diagnosed and repaired, most of the cases have been shown to decrease the stress on the heart and reverse the pathologic hemodynamics. PMID- 26885435 TI - Traumatic Arteriovenous Fistula of the Scalp in the Left Temporoparietal Region with Intra- and Extracranial Blood Supply. AB - Traumatic AVF of the scalp is a rare abnormal vascular disease. It is defined as a communication between the high flow arterial system and the low flow venous network, which directly connects the arterial feeding vessels of the scalp and the draining veins without an intervening capillary bed. The superficial temporal artery (STA) was involved in 90% of the cases, and 71% of the patients only had one dominant feeding STA. Here, we report the case of a rare large traumatic arteriovenous fistula (AVF) of the scalp that is fed by intra- and extracranial blood supply. The clinical and radiological features are presented, and the possible pathogenesis and surgical technique are discussed. PMID- 26885436 TI - Renal Insufficiency and Early Bystander CPR Predict In-Hospital Outcomes in Cardiac Arrest Patients Undergoing Mild Therapeutic Hypothermia and Cardiac Catheterization: Return of Spontaneous Circulation, Cooling, and Catheterization Registry (ROSCCC Registry). AB - Objective. Out of hospital cardiac arrest (OHCA) patients are a critically ill patient population with high mortality. Combining mild therapeutic hypothermia (MTH) with early coronary intervention may improve outcomes in this population. The aim of this study was to evaluate predictors of mortality in OHCA patients undergoing MTH with and without cardiac catheterization. Design. A retrospective cohort of OHCA patients who underwent MTH with catheterization (MTH + C) and without catheterization (MTH + NC) between 2006 and 2011 was analyzed at a single tertiary care centre. Predictors of in-hospital mortality and neurologic outcome were determined. Results. The study population included 176 patients who underwent MTH for OHCA. A total of 66 patients underwent cardiac catheterization (MTH + C) and 110 patients did not undergo cardiac catheterization (MTH + NC). Immediate bystander CPR occurred in approximately half of the total population. In the MTH + C and MTH + NC groups, the in-hospital mortality was 48% and 78%, respectively. The only independent predictor of in-hospital mortality for patients with MTH + C, after multivariate analysis, was baseline renal insufficiency (OR = 8.2, 95% CI 1.8-47.1, and p = 0.009). Conclusion. Despite early cardiac catheterization, renal insufficiency and the absence of immediate CPR are potent predictors of death and poor neurologic outcome in patients with OHCA. PMID- 26885437 TI - Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses. AB - Intravenous immunoglobulins (IVIGs), a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies), as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses. PMID- 26885438 TI - Predictive Response Value of Pre- and Postchemoradiotherapy Variables in Rectal Cancer: An Analysis of Histological Data. AB - Background. Neoadjuvant chemoradiotherapy (nCRT) followed by curative surgery in locally advanced rectal cancer (LARC) improves pelvic disease control. Survival improvement is achieved only if pathological response occurs. Mandard tumor regression grade (TRG) proved to be a valid system to measure nCRT response. Potential predictive factors for Mandard response are analyzed. Materials and Methods. 167 patients with LARC were treated with nCRT and curative surgery. Tumor biopsies and surgical specimens were reviewed and analyzed regarding mitotic count, necrosis, desmoplastic reaction, and inflammatory infiltration grade. Surgical specimens were classified according to Mandard TRG. The patients were divided as "good responders" (Mandard TRG1-2) and "bad responders" (Mandard TRG3-5). According to results from our previous data, good responders have better prognosis than bad responders. We examined predictive factors for Mandard response and performed statistical analysis. Results. In univariate analysis, distance from anal verge and ten other postoperative variables related with nCRT tumor response had predictive value for Mandard response. In multivariable analysis only mitotic count, necrosis, and differentiation grade in surgical specimen had predictive value. Conclusions. There is a lack of clinical and pathological preoperative variables able to predict Mandard response. Only postoperative pathological parameters related with nCRT response have predictive value. PMID- 26885439 TI - Comparison of the Effect of Two Purification Methods on the Immunogenicity of Recombinant Outer Membrane Protein H of Pasteurella multocida Serovar A:1. AB - Recombinant outer membrane protein H (rOmpH) of Pasteurella multocida strain X-73 can be purified using affinity chromatography but this adversely affects its immunogenicity. The current study presents the results from an intervention study comparing the immunogenicity of rOmpH purified using electroelution with rOmpH purified using affinity chromatography and native OmpH purified using electroelution and a nonimmunized control group. Chickens immunized with rOmpH purified using electroelution produced the highest ELISA antibody levels against P. multocida strains. Chickens in each of the 5 treatment groups were split into two subgroups for challenge with two different P. multocida strains. The average number of adhesions to CEF cells was statistically significantly lower in sera from chickens immunized with rOmpH or native OmpH purified using electroelution than in those of the three other treatment groups. The survival amongst chickens immunized with rOmpH or native OmpH purified using electroelution indicated high levels of protection. In contrast, survival probability was zero or low in the groups immunized with rOmpH purified using affinity chromatography and in the nonimmunized group. These findings show that the rOmpH purified using electroelution retains its immunogenicity and stimulates high levels of protection in chickens against P. multocida infection. PMID- 26885440 TI - Comparative Study of Novel Ratio Spectra and Isoabsorptive Point Based Spectrophotometric Methods: Application on a Binary Mixture of Ascorbic Acid and Rutin. AB - This paper presents novel methods for spectrophotometric determination of ascorbic acid (AA) in presence of rutin (RU) (coformulated drug) in their combined pharmaceutical formulation. The seven methods are ratio difference (RD), isoabsorptive_RD (Iso_RD), amplitude summation (A_Sum), isoabsorptive point, first derivative of the ratio spectra ((1)DD), mean centering (MCN), and ratio subtraction (RS). On the other hand, RU was determined directly by measuring the absorbance at 358 nm in addition to the two novel Iso_RD and A_Sum methods. The work introduced in this paper aims to compare these different methods, showing the advantages for each and making a comparison of analysis results. The calibration curve is linear over the concentration range of 4-50 MUg/mL for AA and RU. The results show the high performance of proposed methods for the analysis of the binary mixture. The optimum assay conditions were established and the proposed methods were successfully applied for the assay of the two drugs in laboratory prepared mixtures and combined pharmaceutical tablets with excellent recoveries. No interference was observed from common pharmaceutical additives. PMID- 26885441 TI - C4.4A as a biomarker of head and neck squamous cell carcinoma and correlated with epithelial mesenchymal transition. AB - C4.4A, a member of the Ly6/uPAR family of membrane proteins, has been identified as a metastasis-associated molecule, but little is known about its actual expression and possible function in head and neck squamous cell carcinoma (HNSCC). To explore diagnostic and prognostic roles of C4.4A in HNSCC, we investigated the expression of C4.4A in human HNSCC tissue array which contains 43 HNSCC, 6 epithelial dysplasia and 16 normal oral mucosa. Expression of C4.4A was significantly increased in epithelial dysplasia and HNSCC when compared with normal oral mucosa. Moreover, high C4.4A expression indicated a rather poor prognosis of HNSCC patients. To better understand the function of C4.4A in HNSCC progression, we investigated epithelial to mesenchymal transition (EMT) associated proteins including transforming growth factor (TGF-beta1), Slug and CD147 in HNSCC. The expression of TGF-beta1, Slug, and CD147 was significantly increased in HNSCC when compared with normal oral mucosa. Meanwhile, the expression of C4.4A was significantly correlated with TGF-beta1, Slug, and CD147 in HNSCC tissue array. Furthermore, knockdown of C4.4A decreased the cell invasion and migration in CAL27 cell line and suppressed the EMT with increased E cadherin and decreased N-cadherin and Slug. Our study demonstrated that C4.4A was a potential marker for prognosis of HNSCC, and C4.4A participated in EMT program in HNSCC progression. PMID- 26885442 TI - TOX gene: a novel target for human cancer gene therapy. AB - Thymocyte selection-associated high mobility group box factor (TOX) is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. TOX encodes a nuclear protein of the high mobility group box superfamily. It contains a DNA-binding domain, which allows it to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. Previous studies have shown that TOX play important roles in immune system. More recently, several studies have described TOX expression is frequently upregulated in diverse types of human tumors and the overregulation often associates with tumor progression. Moreover, TOXis involved in the control of cell apoptosis, growth, metastasis, DNA repair and so on. In this review, we provide an overview of current knowledge concerning the role of TOX in tumor development and progression biology function. To our knowledge, this is the first review about the role of thisnew oncogene in tumor development and progression. PMID- 26885444 TI - Safety and efficacy of quadrapeutics versus chemoradiation in head and neck carcinoma xenograft model. AB - Chemoradiation is the strongest anti-tumor therapy but in resistant unresectable cancers it often lacks safety and efficacy. We compared our recently developed cell-level combination approach, quadrapeutics, to chemoradiation therapy to establish pre-clinical data for its biodistribution, safety and efficacy in head and neck squamous cell carcinoma (HNSCC), as a clinically challenging aggressive and resistant cancer. In vitro and in vivo models of four carcinomas were treated with standard chemoradiation and quadrapeutics using identical drug and radiation doses. We applied liposomal cisplatin or doxorubicin, colloidal gold, near infrared laser pulses and radiation, all at low safe doses. The final evaluation used a xenograft model of HNSCC. Quadrapeutics enhanced standard chemoradiation in vitro by reducing head and neck cancer cell proliferation by 1000-fold, inhibiting tumor growth in vivo by 34-fold and improving animal survival by 5 fold, and reducing the side effects to a negligible level. In quadrapeutics, we observed an "inversion" of the drug efficacy of two standard drugs: doxorubicin, a low efficacy drug for the cancers studied, was two times more efficient than cisplatin, the first choice drug in clinic for HNSCC. The radical therapeutic gain of quadrapeutics resulted from the intracellular synergy of the four components employed which we administered in a specific sequence, while the reduction in the toxicity was due to the low doses of all four components. The biodistribution, safety and efficacy data for quadrapeutics in HNSCC ensure its high translational potential and justify the possibility of clinical trials. PMID- 26885443 TI - The association of mammalian DREAM complex and HPV16 E7 proteins. AB - The mammalian DREAM (Drosophila, RB, E2F, and Myb) complex was discovered in 2004 by several research groups. It was initially identified in Drosophila followed by Caenorhaditis elegans and later in mammalian cells. The composition of DREAM is temporally regulated during cell cycle; being associated with E2F-4 and either p107 or p130 in G0/G1 (repressive DREAM complexes) and with B-myb transcription factor in S/G2 (activator DREAM complex). High risk human papillomavirus (HPV) E6 and E7 oncoproteins expression are important for malignant transformation of cervical cancer cells. In particular, the E7 of high risk HPV binds to pRB family members (pRB, p107 and p130) for degradation. It has recently been discovered that the p107 and p130 'pocket proteins' are members of mammalian DREAM complexes. With this understanding, we would like to hypothesise the mammalian DREAM complex could plays a critical role for malignant transformation in cervical cancer cells. PMID- 26885445 TI - Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer. AB - Volasertib (BI 6727), a highly selective and potent inhibitor of PLK1, has shown broad antitumor activities in the preclinical and clinical studies for the treatment of several types of cancers. However, the anticancer effect of volasertib on cervical cancer cells is still unknown. In the present study, we show that volasertib can markedly induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the decreased protein expressions of PLK1 substrates survivin and wee1 in human cervical cancer cells. Furthermore, volasertib also enhances the intracellular reactive oxidative species (ROS) levels, and pretreated with ROS scavenger N-acety-L-cysteine totally blocks ROS generation but partly reverses volasertib-induced apoptosis. In addition, volasertib significantly potentiates the activity of cisplatin to inhibit the growth of cervical cancer in vitro and in vivo. In brief, volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer, suggesting the combination of volasertib and cisplatin may be a promising strategy for the treatment of patients with cervical cancer. PMID- 26885446 TI - Carglumic acid promotes apoptosis and suppresses cancer cell proliferation in vitro and in vivo. AB - Drug repurposing is a therapeutic strategy that applies drugs to treat different diseases based on new therapeutic function. Carglumic acid (Carbaglu; Orphan Europe) is an orphan drug approved by the FDA for hyperammonemia. Administration of carglumic acid for treatment of hyperammonemia has few side effects and has been used for 10 years to effectively treat hyperammonemia symptoms of both adult and pediatric patients. Here, we tested the potential of carglumic acid to be repurposed as an anticancer agent and showed that carglumic acid promotes apoptosis and inhibits cancer cell growth ina wide variety of human cancers, including pancreatic ductal adenocarcinoma, triple-negative breast cancer (TNBC), hepatoma, and lung cancer. Our data from in vivo models indicates that orally taking 10% of the carglumic acid dose currently used for the treatment of hyperammonemia ise ffective to suppress the growth of pancreatic ductal adenocarcinomaand TNBC. If given intravenously, only 5% of the carglumic acid doseis needed to be effective against TNBC. These findings suggest that carglumic acid may serve as a safe and effective therapeutic to treat both TNBC and pancreatic cancer. PMID- 26885448 TI - Preclinical evaluation of afatinib (BIBW2992) in esophageal squamous cell carcinoma (ESCC). AB - Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer worldwide. Epidermal growth factor receptors (EGFR) are often overexpressed in esophageal cancers, thus anti-EGFR inhibitors have been evaluated in ESCC. Afatinib was an irreversible inhibitor of these ErbB family receptors. This study characterized the preclinical activity of afatinib in five ESCC cell lines: HKESC 1, HKESC-2, KYSE510, SLMT-1 and EC-1. ESCC cell lines were sensitive to afatinib with IC50 concentrations at lower micro-molar range (at 72 hour incubation: HKESC 1 = 0.002 MUM, HKESC-2 = 0.002 MUM, KYSE510 = 1.090 MUM, SLMT-1 = 1.161 MUM and EC-1 = 0.109 MUM) with a maximum growth inhibition over 95%. Afatinib can strongly induce G0/G1 cell cycle arrest in HKESC-2 and EC-1 in a dose- and time dependent manner. The phosphorylation of ErbB family downstream effectors such as pAKT, pS6 and pMAPK were significantly inhibited in HKESC-2 and EC-1. Apoptosis was observed in both cell lines at 24 hours after exposure to afatinib, as determined by the presence of cleaved PARP. Afatinib could effectively inhibit HKESC-2 tumor growth in mice without obvious toxicity. Afatinib alone has shown excellent growth inhibitory effect on ESCC in both in vitro and in vivo models, however, no synergistic effect was observed when it was combined with chemotherapeutic agents such as 5-fluorouracil (5-FU) and cisplatin. In summary, afatinib can inhibit cell proliferation effectively by arresting the cells in G0/G1 phase, as well as inducing apoptosis in ESCC. These findings warrant further studies of afatinib as therapeutic agent in treating ESCC. PMID- 26885447 TI - Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells. AB - Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers' great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications. PMID- 26885449 TI - Metformin inhibits salivary adenocarcinoma growth through cell cycle arrest and apoptosis. AB - The inhibitory effects of metformin have been observed in many types of cancer. However, its effect on human salivary gland carcinoma is unknown. The effect of metformin alone or in combination with pp242 (an mTOR inhibitor) on salivary adenocarcinoma cells growth were determined in vitro and in vivo. We found that metformin suppressed HSY cell growth in vitro in a time and dose dependent manner associated with a reduced expression of MYC onco-protein, and the same inhibitory effect of metformin was also confirmed in HSG cells. In association with the reduction of MYC onco-protein, metformin significantly restored p53 tumor suppressor gene expression. The distinctive effects of metformin and PP242 on MYC reduction and P53 restoration suggested that metformin inhibited cell growth through a different pathway from PP242 in salivary carcinoma cells. Furthermore, the anti-tumor efficacy of metformin was confirmed in vivo as indicated by the increases of tumor necrosis and reduced proliferation in xenograft tumors from metformin treated group. For the first time, the inhibitory effect of metformin on human salivary gland tumor cells was documented. Moreover, metformin inhibitory effects were enhanced by mTOR inhibitor suggesting that metformin and mTOR inhibitor utilize distinctive signaling pathways to suppress salivary tumor growth. PMID- 26885451 TI - Selective expression of constitutively active pro-apoptotic protein BikDD gene in primary mammary tumors inhibits tumor growth and reduces tumor initiating cells. AB - Our previous study showed that specifically delivering BikDD, a constitutive active mutant of pro-apoptotic protein Bik, to breast cancer cell xenografts in immunocompromised mice has a potent activity against tumor initiating cells (TICs), and that the combination between tyrosine kinase inhibitors (TKI) and BikDD gene therapy yielded synergistic effect on EGFR and HER2 positive breast cancer cells in immunodeficient nude mice. Those encouraging results have allowed us to propose a clinical trial using the liposome-complexing plasmid DNA expressing BikDD gene which has been approved by the NIH RAC Advisory committee. However, it is imperative to test whether systemic delivery of BikDD-expressing plasmid DNAs with liposomes into immunocompetent mice has therapeutic efficacy and tolerable side effects as what we observed in the nude mice model. In this study, we investigated the effects of BikDD gene-therapy on the primary mammary tumors, especially on tumor initiating cells (TICs), of a genetically engineered immunocompetent mouse harboring normal microenvironment and immune response. The effects on TIC population in tumors were determined by FACS analysis with different sets of murine specific TIC markers, CD49f(high)CD61(high) and CD24(+)Jagged1(-). First we showed in vitro that ectopic expression of BikDD in murine N202 cells derived from MMTV-HER2/Neu transgenic mouse tumors induced apoptosis and decreased the number of TICs. Consistently, systemic delivery of VISA-Claudin4-BikDD by liposome complexes significantly inhibited mammary tumor growth and slowed down residual tumor growth post cessation of therapy in MMTV HER2/Neu transgenic mice compared to the controls. In addition, the anti-tumor effects of BikDD in vivo were consistent with decreased TIC population assessed by FACS analysis and in vitro tumorsphere formation assay of freshly isolated tumor cells. Importantly, systemic administration of BikDD did not cause significant cytotoxic response in standard toxicity assays or body weight changes. Taken together, our findings validated that selective expression of BikDD in the primary mammary tumors in immunocompetent hosts significantly reduced tumor burden and inhibited the residual tumor growth at off-therapy stage by eliminating TICs. Hence, the VISA-Claudin4-BikDD-mediated gene therapy is worthy of further investigation in breast cancer clinical trials. PMID- 26885450 TI - Oncolytic newcastle disease virus triggers cell death of lung cancer spheroids and is enhanced by pharmacological inhibition of autophagy. AB - Lung cancer stem cells (CSCs) have recently been isolated from lung cancer patient samples and have been reported to be responsible for tumor initiation, treatment resistance and tumor recurrence. We have previously shown that oncolytic Newcastle disease virus (NDV), strain FMW (NDV/FMW) induces apoptosis in drug-resistant lung cancer cells. However, how NDV exerts its oncolytic effect on lung CSCs remains to be investigated. Here we show that NDV/FMW replicates in, and lyses CSC-enriched lung cancer spheroids and inhibits the 3D growth potential of lung cancer spheroid and agar colonies. We demonstrate that NDV/FMW triggers caspase-dependent apoptosis in lung cancer spheroids as shown by increased caspase-3 processing and Poly (ADP-ribose) polymerase (PARP) cleavage. Notably, NDV/FMW infection results in the degradation of microtubule-associated protein 1 light chain 3 (LC3) II and P62, two hallmarks of autophagy maturation, indicating that NDV/FMW promotes autophagy flux in lung cancer cell spheroids. This was further confirmed by the appearance of an increased number of double-membrane vesicles as detected by transmission electron microscopy. We also show that NDV/FMW promotes autophagy degradation in lung cancer spheroids via inhibition of the AKT/mTOR pathway. In addition, treatment of spheroids with the autophagy inhibitor, chloroquine increases NDV/FMW-induced cytotoxicity. Collectively, our data show that oncolytic NDV/FMW may be a potential strategy in targeting lung CSCs. PMID- 26885452 TI - MiR-610 inhibits cell proliferation and invasion in colorectal cancer by repressing hepatoma-derived growth factor. AB - MicroRNAs (miRNAs) act as key regulators of gene expression and their dysregulation is linked to carcinogenesis and tumor progression. MiR-610 has been implicated as an anti-tumor miRNA in multiple types of cancers. However, its biological role and the underlying mechanism in colorectal cancer (CRC) have not been well explored. In this study, we report that miR-610 expression is decreased in CRC samples while ectopic expression of miR-610 suppresses cell proliferation, migration and invasion, and influences the expression of epithelial-mesenchymal transition (EMT)-associated proteins by up-regulating E-cadherin expression and down-regulating vimentin expression. Using a luciferase reporter assay, we reveal that miR-610 directly targets hepatoma-derived growth factor (HDGF) by binding to its 3'UTR. A negative correlation was also observed between miR-610 and HDGF expression in CRC tissues. Further studies show that inhibition of HDGF recapitulates the anti-tumor function of miR-610, whereas re-expression of HDGF partially abrogates the inhibitory effects of miR-610. Collectively, our findings indicate that miR-610 exerts its function by directly targeting HDGF. The miR 610/HDGF axis is a novel therapeutic target for CRC. PMID- 26885454 TI - Increased NUCKS expression is a risk factor for poor prognosis and recurrence in endometrial cancer. AB - Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) was reported to function as a potential biomarker in various tumors. Thus, we aimed to explore the expression of NUCKS in endometrial cancer (EC) and its clinical significance using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). qRT-PCR results showed that NUCKS mRNA expression gradually elevated from normal endometrium to atypical endometrial hyperplasia, and to EC (P < 0.05 between each group). NUCKS overexpression was strongly associated with FIGO stage (P = 0.002), histologic grade (P = 0.029), lympho-vascular space involvement (P = 0.014), lymph node metastasis (P = 0.019), and recurrence (P < 0.001). Cox multivariate analysis revealed that NUCKS overexpression was an independent factor for overall survival and recurrence-free survival (P < 0.001 for both). Multivariate logistic regression suggested that recurrence was independently correlated with NUCKS overexpresion (P = 0.039), FIGO stage (P = 0.002), and lymph node metastasis (P = 0.002). In summary, NUCKS overexpression may function as a potential biomarker for prognosis especially for recurrence in ECs. PMID- 26885456 TI - Nanoinformatics for environmental health and biomedicine. PMID- 26885457 TI - Effects of spin-orbit coupling and many-body correlations in STM transport through copper phthalocyanine. AB - The interplay of exchange correlations and spin-orbit interaction (SOI) on the many-body spectrum of a copper phtalocyanine (CuPc) molecule and their signatures in transport are investigated. We first derive a minimal model Hamiltonian in a basis of frontier orbitals that is able to reproduce experimentally observed singlet-triplet splittings. In a second step SOI effects are included perturbatively. Major consequences of the SOI are the splitting of former degenerate levels and a magnetic anisotropy, which can be captured by an effective low-energy spin Hamiltonian. We show that scanning tunneling microscopy based magnetoconductance measurements can yield clear signatures of both these SOI-induced effects. PMID- 26885453 TI - Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model. AB - The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9 cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9 cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology. PMID- 26885458 TI - Blue and white light emission from zinc oxide nanoforests. AB - Blue and white light emission is observed when high voltage stress is applied using micrometer-separated tungsten probes across a nanoforest formed of ZnO nanorods. The optical spectrum of the emitted light consistently shows three fine peaks with very high amplitude in the 465-485 nm (blue) range, corresponding to atomic transitions of zinc. Additional peaks with smaller amplitudes in the 330 650 nm range and broad spectrum white light is observed depending on the excitation conditions. The spatial and spectral distribution of the emitted light, with pink-orange regions identifying percolation paths in some cases and high intensity blue and white light with center to edge variations in others, indicate that multiple mechanisms lead to light emission. Under certain conditions, the tungsten probe tips used to make electrical contact with the ZnO structures melt during the excitation, indicating that the local temperature can exceed 3422 degrees C, which is the melting temperature of tungsten. The distinct and narrow peaks in the optical spectra and the abrupt increase in current at high electric fields suggest that a plasma is formed by application of the electrical bias, giving rise to light emission via atomic transitions in gaseous zinc and oxygen. The broad spectrum, white light emission is possibly due to the free electron transitions in the plasma and blackbody radiation from molten silicon. The white light may also arise from the recombination through multiple defect levels in ZnO or due to the optical excitation from solid ZnO. The electrical measurements performed at different ambient pressures result in light emission with distinguishable differences in the emission properties and I V curves, which also indicate that the dielectric breakdown of ZnO, sublimation, and plasma formation processes are the underlying mechanisms. PMID- 26885455 TI - Application of biclustering of gene expression data and gene set enrichment analysis methods to identify potentially disease causing nanomaterials. AB - BACKGROUND: The presence of diverse types of nanomaterials (NMs) in commerce is growing at an exponential pace. As a result, human exposure to these materials in the environment is inevitable, necessitating the need for rapid and reliable toxicity testing methods to accurately assess the potential hazards associated with NMs. In this study, we applied biclustering and gene set enrichment analysis methods to derive essential features of altered lung transcriptome following exposure to NMs that are associated with lung-specific diseases. Several datasets from public microarray repositories describing pulmonary diseases in mouse models following exposure to a variety of substances were examined and functionally related biclusters of genes showing similar expression profiles were identified. The identified biclusters were then used to conduct a gene set enrichment analysis on pulmonary gene expression profiles derived from mice exposed to nano titanium dioxide (nano-TiO2), carbon black (CB) or carbon nanotubes (CNTs) to determine the disease significance of these data-driven gene sets. RESULTS: Biclusters representing inflammation (chemokine activity), DNA binding, cell cycle, apoptosis, reactive oxygen species (ROS) and fibrosis processes were identified. All of the NM studies were significant with respect to the bicluster related to chemokine activity (DAVID; FDR p-value = 0.032). The bicluster related to pulmonary fibrosis was enriched in studies where toxicity induced by CNT and CB studies was investigated, suggesting the potential for these materials to induce lung fibrosis. The pro-fibrogenic potential of CNTs is well established. Although CB has not been shown to induce fibrosis, it induces stronger inflammatory, oxidative stress and DNA damage responses than nano-TiO2 particles. CONCLUSION: The results of the analysis correctly identified all NMs to be inflammogenic and only CB and CNTs as potentially fibrogenic. In addition to identifying several previously defined, functionally relevant gene sets, the present study also identified two novel genes sets: a gene set associated with pulmonary fibrosis and a gene set associated with ROS, underlining the advantage of using a data-driven approach to identify novel, functionally related gene sets. The results can be used in future gene set enrichment analysis studies involving NMs or as features for clustering and classifying NMs of diverse properties. PMID- 26885460 TI - Probing the local environment of a single OPE3 molecule using inelastic tunneling electron spectroscopy. AB - We study single-molecule oligo(phenylene ethynylene)dithiol junctions by means of inelastic electron tunneling spectroscopy (IETS). The molecule is contacted with gold nano-electrodes formed with the mechanically controllable break junction technique. We record the IETS spectrum of the molecule from direct current measurements, both as a function of time and electrode separation. We find that for fixed electrode separation the molecule switches between various configurations, which are characterized by different IETS spectra. Similar variations in the IETS signal are observed during atomic rearrangements upon stretching of the molecular junction. Using quantum chemistry calculations, we identity some of the vibrational modes which constitute a chemical fingerprint of the molecule. In addition, changes can be attributed to rearrangements of the local molecular environment, in particular at the molecule-electrode interface. This study shows the importance of taking into account the interaction with the electrodes when describing inelastic contributions to transport through single molecule junctions. PMID- 26885459 TI - Calculations of helium separation via uniform pores of stanene-based membranes. AB - The development of low energy cost membranes to separate He from noble gas mixtures is highly desired. In this work, we studied He purification using recently experimentally realized, two-dimensional stanene (2D Sn) and decorated 2D Sn (SnH and SnF) honeycomb lattices by density functional theory calculations. To increase the permeability of noble gases through pristine 2D Sn at room temperature (298 K), two practical strategies (i.e., the application of strain and functionalization) are proposed. With their high concentration of large pores, 2D Sn-based membrane materials demonstrate excellent helium purification and can serve as a superior membrane over traditionally used, porous materials. In addition, the separation performance of these 2D Sn-based membrane materials can be significantly tuned by application of strain to optimize the He purification properties by taking both diffusion and selectivity into account. Our results are the first calculations of He separation in a defect-free honeycomb lattice, highlighting new interesting materials for helium separation for future experimental validation. PMID- 26885461 TI - Large area scanning probe microscope in ultra-high vacuum demonstrated for electrostatic force measurements on high-voltage devices. AB - BACKGROUND: The resolution in electrostatic force microscopy (EFM), a descendant of atomic force microscopy (AFM), has reached nanometre dimensions, necessary to investigate integrated circuits in modern electronic devices. However, the characterization of conducting or semiconducting power devices with EFM methods requires an accurate and reliable technique from the nanometre up to the micrometre scale. For high force sensitivity it is indispensable to operate the microscope under high to ultra-high vacuum (UHV) conditions to suppress viscous damping of the sensor. Furthermore, UHV environment allows for the analysis of clean surfaces under controlled environmental conditions. Because of these requirements we built a large area scanning probe microscope operating under UHV conditions at room temperature allowing to perform various electrical measurements, such as Kelvin probe force microscopy, scanning capacitance force microscopy, scanning spreading resistance microscopy, and also electrostatic force microscopy at higher harmonics. The instrument incorporates beside a standard beam deflection detection system a closed loop scanner with a scan range of 100 MUm in lateral and 25 MUm in vertical direction as well as an additional fibre optics. This enables the illumination of the tip-sample interface for optically excited measurements such as local surface photo voltage detection. RESULTS: We present Kelvin probe force microscopy (KPFM) measurements before and after sputtering of a copper alloy with chromium grains used as electrical contact surface in ultra-high power switches. In addition, we discuss KPFM measurements on cross sections of cleaved silicon carbide structures: a calibration layer sample and a power rectifier. To demonstrate the benefit of surface photo voltage measurements, we analysed the contact potential difference of a silicon carbide p/n-junction under illumination. PMID- 26885463 TI - pH-Triggered release from surface-modified poly(lactic-co-glycolic acid) nanoparticles. AB - Nanoparticles (NP) of poly(lactic-co-glycolic acid) (PLGA) represent a promising biodegradable drug delivery system. We suggest here a two-step release system of PLGA nanoparticles with a pH-tunable polymeric shell, providing an initial pH triggered step, releasing a membrane-toxic cationic compound. PLGA nanoparticles are coated by polyelectrolytes using the layer-by-layer self-assembly technique, employing poly(acrylic acid) (PAA) as a pH-sensitive component and poly(diallyldimethylammonium chloride) (PDADMAC) as the releasable polycation. The pH during multilayer deposition plays a major role and influences the titration curve of the layer system. The pH-tunability of PAA is intensively investigated with regard to the pH region, in which the particle system becomes uncharged. The isoelectric point can be shifted by employing suitable deposition pH values. The release is investigated by quantitative (1)H NMR, yielding a pH dependent release curve. A release of PDADMAC is initiated by a decrease of the pH value. The released amount of polymer, as quantified by (1)H NMR analysis, clearly depends on the pH value and thus on the state of deprotonation of the pH sensitive PAA layer. Subsequent incubation of the nanoparticles with high concentrations of sodium chloride shows no further release and thus demonstrates the pH-driven release to be quantitative. PMID- 26885464 TI - Solution of fractional bioheat equation in terms of Fox's H-function. AB - Present paper deals with the solution of time and space fractional Pennes bioheat equation. We consider time fractional derivative and space fractional derivative in the form of Caputo fractional derivative of order [Formula: see text] and Riesz-Feller fractional derivative of order [Formula: see text] respectively. We obtain solution in terms of Fox's H-function with some special cases, by using Fourier-Laplace transforms. PMID- 26885462 TI - Chemiresistive/SERS dual sensor based on densely packed gold nanoparticles. AB - Chemiresistors are a class of sensitive electrical devices capable of detecting (bio)chemicals by simply monitoring electrical resistance. Sensing based on surface enhanced Raman scattering (SERS) represents a radically different approach, in which molecules are optically detected according to their vibrational spectroscopic fingerprint. Despite different concepts are involved, one can find in the literature examples from both categories reporting sensors made of gold nanoparticles. The same building blocks appear because both sensor classes share a common principle: nanometric interparticle gaps are needed, for electron tunneling in chemiresistors, and for enhancing electromagnetic fields by plasmon coupling in SERS-based sensors. By exploiting such nano-gaps in self assembled films of gold nanoparticles, we demonstrate the proof of concept of a dual electrical/optical sensor, with both chemiresistive and SERS capabilities. The proposed device is realized by self-assembling 15 nm gold nanoparticles into few micrometers-wide strips across commercially available interdigitated electrodes. The dual-mode operation of the device is demonstrated by the detection of a biologically relevant model analyte, 4-mercaptophenyl boronic acid. PMID- 26885465 TI - Antibacterial activity of an acidic phospholipase A2 (NN-XIb-PLA2) from the venom of Naja naja (Indian cobra). AB - The resistance of bacteria against the use of conventional antibiotics has become a serious threat to public health and considering the associated side effect with antibiotics; new strategies to find and develop new molecules with novel modes of action has received grate attention in recent years. In this study, when the antibacterial potential of an acidic protein-NN-XIb-PLA2 (Naja naja venom phospholipase A2 fraction-XIb) of Naja naja venom was evaluated, it showed significant bactericidal action against the human pathogenic strains tested. It inhibited more effectively the gram positive bacteria like Staphylococcus aureus and Bacillus subtilis, when compared to gram negative bacteria like Escherichia coli, Vibrio cholerae, Klebsiell pneumoniae and Salmonella paratyphi. It inhibited the bacterial growth, with a MIC values ranging from 17 to 20 ug/ml. It was interesting to observe that NN-XIb-PLA2 showed comparable antibacterial activity to the used standards antibiotics. It was found that their was a strong correlation between PLA2 activities, hemolytic and antibacterial activity. Furthermore, it is found that in the presence of p-bromophenacyl bromide (p-BPB), there is a significant decrease in enzymatic activity and associated antibacterial activities, suggesting that a strong association exists between catalytic activity and antimicrobial effects, which thereby destabilize the membrane bilayer. These studies encourage further in dept study on molecular mechanisms of bactericidal properties of NN-XIb-PLA2 and thereby help in development of this protein into a possible therapeutic lead molecule for treating bacterial infections. PMID- 26885466 TI - Did Ugo Foscolo suffer from chronic renal insufficiency? AB - Ugo Foscolo, was an Italian poet whose works rank among the masterpieces of Italian literature. Talented and well educated in philosophy, classics, and Italian literature, Foscolo gave literary expression to his ideological aspirations and to the numerous amorous experiences in odes, sonnets, plays, poems and an epistolary novel. Concurrent with his rich literary output, Foscolo's correspondence represents a unique perspective from which to monitor his literary and political views and investigate aspects of his everyday life. Among other interesting information, one can find elements of Foscolo's medical history which is generally unknown. Based on his testimonies we suggest that he suffered of longstanding bladder outlet obstruction presumably due to urethral stricture. In the present article we investigate the possibility that chronic bladder outlet obstruction and the consequent renal insufficiency was attributed to the death of Ugo Foscolo. PMID- 26885468 TI - Isolated third ventricle glioblastoma. AB - INTRODUCTION: Glioblastoma is the most common and the most malignant type of gliomas. Cerebral hemispheres are usual locations for gliomas. Isolated third ventricular presentation is very rare for glioblastomas. A new case of isolated third ventricular glioblastoma has been presented in this report. CASE DESCRIPTION: A 36-year-old woman was admitted to outpatient clinic with headache, blurred vision and confusion. A head CT scan and MRI had showed third ventricular mass lesion with obstructive hydrocephalus. Previous to her admission to our clinic, a ventriculo-peritoneal shunt had been inserted and her hydrocephalus had been relieved to some extent in acute settings. In our clinic, stereotactic biopsy was performed and a second ventriculoperitoneal shunt was inserted from the opposite site. Histopathological diagnosis was glioblastoma. Radiotherapy and chemotherapy were started immediately after the surgery. Patient's hydrocephalus has resolved and she was well at post-operative 6th month. DISCUSSION AND EVALUATION: In differential diagnosis list of the tumors presenting in the third ventricle, there are plenty of tumors such as colloid cyst, meningioma, germinoma, craniopharyngioma, lymphoma, choroid plexus papilloma, subependymal giant cell astrocytoma, chiasmatic and hypothalamic benign astrocytoma. Ring enhancement of this region pathology is a peculiar sign for glioblastoma, yet not pathognomonic. Tumor histology is crucial to yield the final diagnosis. CONCLUSION: Management of obstructive hydrocephalus, making histopathological diagnosis, starting adjuvant radiotherapy and chemotherapy in isolated third ventricular glioblastomas is a safe and effective approach when we consider malignant nature and intractable progress of glioblastomas. PMID- 26885467 TI - Role of patient and tumor characteristics in sentinel lymph node metastasis in patients with luminal early breast cancer: an observational study. AB - Predicting the risk of sentinel lymph node (SLN) metastasis is important for clinical decision-making in the setting of early breast cancer (EBC). This study is aimed to identify tumor and patient characteristics that influenced the SLN metastatic involvement, with a focus on luminal subtypes. An observational study including women treated for EBC from 2005 to 2013 was conducted. Regression analyses were used to assess the association between SLN metastasis and age, menopausal status, tumor size, histological grading, presence of extensive "in situ" carcinoma components, lymphovascular invasion (LVI), and expression of Ki 67, hormone receptors, and HER2. Of 345 women, 84 (24.3 %) had at least one SLN metastasis; 63.1 % were macrometastases. Among all patients, 31.6 % exhibited LVI. In univariate analyses, tumor size, histological grade, and LVI were associated with SLN metastasis. The multivariate model confirmed only the association between LVI and SLN status (OR 3.27, 95 % CI 1.85-5.68; p < 0.0001). Luminal subtypes were detected in 86.1 % of women. In this subgroup, the multivariate model confirmed a significant relationship between LVI and SLN status (OR 3.47, 95 % CI 1.90-6.33; p < 0.0001). Since a proper histopathological assessment of LVI is not possible prior to surgery, this factor cannot be used to guide decisions on performing SLN biopsies. Nevertheless, when a SLN biopsy is refused or contraindicated, an LVI assessment on an excisional biopsy of the tumor could facilitate prognosis determination and treatment management. PMID- 26885469 TI - Antibacterial activity of aquatic gliding bacteria. AB - The study aimed to screen and isolate strains of freshwater aquatic gliding bacteria, and to investigate their antibacterial activity against seven common pathogenic bacteria. Submerged specimens were collected and isolated for aquatic gliding bacteria using four different isolation media (DW, MA, SAP2, and Vy/2). Gliding bacteria identification was performed by 16S rRNA gene sequencing and phylogenetic analysis. Crude extracts were obtained by methanol extraction. Antibacterial activity against seven pathogenic bacteria was examined by agar well diffusion assay. Five strains of aquatic gliding bacteria including RPD001, RPD008, RPD018, RPD027 and RPD049 were isolated. Each submerged biofilm and plastic specimen provided two isolates of gliding bacteria, whereas plant debris gave only one isolate. Two strains of gliding bacteria were obtained from each DW and Vy/2 isolation medium, while one strain was obtained from the SAP2 medium. Gliding bacteria strains RPD001, RPD008 and RPD018 were identified as Flavobacterium anhuiense with 96, 82 and 96 % similarity, respectively. Strains RPD049 and RPD027 were identified as F. johnsoniae and Lysobacter brunescens, respectively, with similarity equal to 96 %. Only crude extract obtained from RPD001 inhibited growth of Listeria monocytogenes (MIC 150 ug/ml), Staphylococcus aureus (MIC 75 ug/ml) and Vibrio cholerae (MIC 300 ug/ml), but showed weak inhibitory effect on Salmonella typhimurium (MIC > 300 ug/ml). Gliding bacterium strain RPD008 should be considered to a novel genus separate from Flavobacterium due to its low similarity value. Crude extract produced by RPD001 showed potential for development as a broad antibiotic agent. PMID- 26885470 TI - Clinical and Research Implications of Gambling Disorder in DSM-5. AB - The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders contains significant changes related to the diagnosis of gambling problems. These changes include the renaming of the disorder from pathological gambling to gambling disorder, reclassification of gambling disorder from an impulse control disorder to an addictive disorder, removal of the illegal acts criterion, lowering diagnostic threshold to endorsement of four criteria, and recognizing that the course of the disorder is no longer chronic for all diagnosed. This paper reviews the rationale and research support for these changes. Implications of the new revisions for both research and clinical practice are reviewed, including a discussion about future directions for research efforts. PMID- 26885471 TI - Significance of residual renal function for phosphate control in chronic hemodialysis patients. AB - BACKGROUND: The aim of this study was to compare mineral metabolism between anuric and nonanuric chronic hemodialysis patients, and determine the differences in phosphate control between the two groups. METHODS: A total of 77 chronic hemodialysis patients were enrolled in this cross-sectional study from January 2012 to February 2012. Patient demographics, laboratory findings, medication histories, and vascular calcification scores were collected. We divided the patients into anuric and nonanuric groups according to the residual renal function and then compared their clinical features. Multivariate binary regression analysis was used in each group to determine the independent factors related to phosphate control. RESULTS: The mean patient age was 59.27+/-13.95 years, and 57.1% of patients were anuric. In anuric patients, dialysis vintage was significantly longer, but the mean Kt/V was not different between groups. Serum phosphate, fibroblast growth factor (FGF)-23, and Ca/P products were significantly higher, and 1,25(OH)2D3 levels were significantly lower in the anuric patients, although the intact parathyroid hormone and 25(OH)D levels were not different. In anuric patients, LnFGF-23 [hazard ratio (HR) 2.894, 95% confidence interval (CI) 1.294-6.474, P=0.010] was an independent factor predictive of phosphate control. However, in the nonanuric patients, glomerular filtration rate (HR 0.409, 95% CI 0.169-0.989, P=0.047) and blood urea nitrogen (HR 1.090, 95% CI 1.014-1.172, P=0.019) were independent factors predictive of phosphate control. CONCLUSION: In chronic hemodialysis patients, preservation of residual renal function is a significant determinant of phosphate control, and the factors associated with phosphate control is different depending on the residual renal function status. In the anuric patients, FGF-23 is most significantly associated with phosphate control; however, glomerular filtration rate and blood urea nitrogen are more important than FGF-23 in the nonanuric HD patients. PMID- 26885472 TI - New classification of membranoproliferative glomerulonephritis: a good start but a long way to go. PMID- 26885473 TI - Anticoagulants and acute kidney injury: clinical and pathology considerations. AB - We have recently identified a new clinical syndrome in patients receiving warfarin for anticoagulation therapy. This syndrome has been named warfarin related nephropathy (WRN), and patients with chronic kidney disease (CKD) appear to be particularly susceptible. WRN is defined as an acute increase in international normalized ratio (INR) to >3.0, followed by evidence of acute kidney injury (AKI) within 1 week of the INR increase. AKI was defined as a sustained increase in serum creatinine of greater than or equal to 0.3 mg/dL. The AKI cannot be explained by any other factors, and the kidney biopsy demonstrates extensive glomerular hemorrhage with tubular obstruction by red blood cells (RBCs). Beyond AKI, WRN is a significant risk factor for mortality within the first 2 months of diagnosis and it accelerates the progression of CKD. We demonstrated that 5/6 nephrectomy in rats is a suitable experimental model to study WRN. Animals treated with warfarin showed an increase in serum creatinine and morphologic findings in the kidney similar to those in humans with WRN. Our recent evidence suggests that novel oral anticoagulants may induce AKI. Diagnosis of WRN may be challenging for a renal pathologist. A few cases with suspected WRN and pathologic considerations are described. PMID- 26885474 TI - Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats. AB - BACKGROUND: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats. METHODS: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension. RESULTS: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. N (omega)-Nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K(+) channels, or tetraethylammonium, an inhibitor of Ca(2+)-activated K(+) channels, significantly reduced biochanin A induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K(+) channels, inhibited the relaxation induced by biochanin A in 2K1C rats, whereas no significant differences were observed in sham rats. CONCLUSION: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K(+) channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K(+) channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension. PMID- 26885476 TI - Insulin resistance is associated with new-onset cardiovascular events in nondiabetic patients undergoing peritoneal dialysis. AB - BACKGROUND: Chronic exposure to high glucose-containing peritoneal dialysis solution and consequent abdominal obesity are potential sources of insulin resistance in patients requiring prevalent peritoneal dialysis. The aim of this study was to elucidate the prognostic values of insulin resistance on new-onset cardiovascular events in nondiabetic patients undergoing prevalent peritoneal dialysis. METHODS: A total of 201 nondiabetic patients undergoing prevalent peritoneal dialysis were recruited. Insulin resistance was assessed by homeostatic model assessment of insulin resistance (HOMA-IR). The primary outcome was new-onset cardiovascular events during the follow-up period. Cox proportional hazard analysis was performed to ascertain the independent prognostic value of HOMA-IR for the primary outcome. RESULTS: The mean age was 53.1 years and male was 49.3% (n=99). The mean HOMA-IR was 2.6+/-2.1. In multivariate linear regression, body mass index (beta=0.169, P=0.011), triglyceride level (beta=0.331, P<0.001), and previous cardiovascular diseases (beta=0.137, P=0.029) were still significantly associated with HOMA-IR. During a mean follow-up duration of 36.8+/-16.2 months, the primary outcome was observed in 36 patients (17.9%). When patients were divided into tertiles according to HOMA-IR, the highest tertile group showed a significantly higher incidence rate for new-onset cardiovascular events compared to the lower two tertile groups (P=0.029). Furthermore, multivariate Cox analysis revealed that HOMA-IR was an independent predictor of the primary outcome (hazard ratio=1.18, 95% confidence interval=1.03 1.35, P=0.014). CONCLUSION: Insulin resistance measured by HOMA-IR was an independent risk factor for new-onset cardiovascular events in nondiabetic patients undergoing prevalent peritoneal dialysis. PMID- 26885475 TI - Reanalysis of membranoproliferative glomerulonephritis patients according to the new classification: a multicenter study. AB - BACKGROUND: All types of membranoproliferative glomerulonephritis (MPGN) are progressive diseases with poor prognoses. Recently, a newly proposed classification of these diseases separated them into immune complex- and complement-mediated diseases. We investigated the frequency of C3 glomerulonephritis among previously diagnosed MPGN patients. METHODS: We conducted a retrospective study of patients diagnosed with MPGN at three tertiary care institutions between 2001 and 2010. We investigated the incidence of complement-mediated disease among patients diagnosed with MPGN. Progressive renal dysfunction was defined as a 50% reduction in the glomerular filtration rate or the need for renal replacement therapy. RESULTS: Among the 3,294 renal biopsy patients, 77 (2.3%) were diagnosed with MPGN; 31 cases were excluded, of which seven were diagnosed with systemic lupus nephritis, and the others were not followed for a minimum of 12 months after biopsy. Based on the new classification, complement-mediated MPGN was diagnosed in two patients (4.3%); only one patient developed progressive renal dysfunction. Among the immune complex-mediated MPGN patients, 17 patients developed progressive renal dysfunction. Serum albumin and creatinine levels at the time of MPGN diagnosis were risk factors of renal deterioration, after adjusting for low C3 levels and nephrotic syndrome. CONCLUSION: Complement-mediated glomerulonephritis was present in 4.3% of patients previously diagnosed with MPGN. PMID- 26885477 TI - Diagnostic accuracy of urine dipstick for proteinuria in older outpatients. AB - BACKGROUND: The urine dipstick is widely used as an initial screening tool for the evaluation of proteinuria; however, its diagnostic accuracy has not yet been sufficiently evaluated. Therefore, we evaluated its diagnostic accuracy using spot urine albumin/creatinine ratio (ACR) and total protein/creatinine ratio (PCR) in proteinuria. METHODS: Using PCR >=0.2 g/g or >=0.5 g/g and ACR >=300 mg/g or >=30 mg/g as the reference standard, we calculated the diagnostic accuracy profile: sensitivity, specificity, positive and negative predictive value, and the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: PCR and ACR were available for 10,348 and 3,873 instances of dipstick testing. The proportions with PCR >=0.2 g/g, >=0.5 g/g and ACR >=300 mg/g, >=30 mg/g were 38.2%, 24.6% and 8.9%, 31.7%, respectively. The AUCs for PCR >=0.2 g/g, >=0.5 g/g, and ACR >=300 mg/g were 0.935 (trace: closest to ideal point), 0.968 (1+), and 0.983 (1+), respectively. Both sensitivity and specificity were >80% except for PCR >=0.5 g/g with trace cutoff. For the reference standard of ACR >=30 mg/g, the AUC was 0.797 (trace) and the sensitivity was 63.5%. CONCLUSION: Urine dipstick test can be used for screening in older outpatients with ACR >=300 mg/g or PCR as the reference standard for proteinuria. However, we cannot recommend the test as a screening tool with ACR >=30 mg/g as the reference owing to its low sensitivity. PMID- 26885478 TI - Clinical outcome of percutaneous thrombectomy of dialysis access thrombosis by an interventional nephrologist. AB - BACKGROUND: Traditionally, the treatment of a thrombosed dialysis access in hemodialysis patients in Korea has been primarily performed by vascular surgeons and interventional radiologists. The objective of this study was to evaluate the outcome of percutaneous thrombectomy procedures performed by an interventional nephrologist. METHODS: From October 2010 to May 2014, 75 consecutive percutaneous thrombectomies were performed on 42 patients treated with maintenance hemodialysis. All percutaneous thrombectomy procedures were performed by an interventional nephrologist in a single hospital in Jeju, Korea. The thrombosed arteriovenous graft and arteriovenous fistula were declotted by thromboaspiration mechanical thrombectomy or pharmacomechanical thrombolysis. Kaplan-Meier survival analysis was performed to analyze the primary and secondary patency after the initial successful thrombectomy. Success and complication rates were identified and compared with the recommendations of the Kidney Disease Dialysis Outcomes Quality Initiative (KDOQI) guideline. RESULTS: The overall clinical success rate was 89.3% (67/75). In the successful cases, the postintervention primary (unassisted) patency rates at 30 days, 90 days, and 180 days were 79.9%, 56.6%, and 25.6%, respectively. The secondary patency rates at 30 days, 90 days, and 180 days were 92.2%, 85.7%, and 83.7%, respectively. There were no major complications, and all complications were treated successfully during the procedure. CONCLUSION: The clinical success rate and primary patency rate at 3 months exceeded the recommendations of the KDOQI guideline, and were comparable to that of other reports. Percutaneous thrombectomy by an interventional nephrologist was safe and effective. PMID- 26885479 TI - A randomized crossover study of single biweekly administration of epoetin-alpha compared with darbepoetin-alpha in chronic kidney disease patients not receiving dialysis. AB - BACKGROUND: Recent evidence demonstrates that high doses of epoetin-alpha (EPO alpha) can be administrated at extended intervals, despite its relatively short serum half-life. However, no prospective randomized trials on the effects of extended dosing intervals of EPO-alpha compared with darbepoetin-alpha (DA-alpha) have been performed. This study was designed to investigate whether a single biweekly (Q2W) administration of a high dose of EPO-alpha is as effective as DA alpha for anemia in chronic kidney disease (CKD) patients not receiving dialysis. METHODS: Sixty non-dialysis CKD patients were equally randomized to either Q2W subcutaneous EPO-alpha (10,000 unit) or DA-alpha (50 MUg) therapy groups for the first 6 weeks. After a 6-week washout period, the participants of the EPO-alpha and DA-alpha treatment groups switched to the alternate regimen for 6 weeks. The mean hemoglobin (Hb) levels after erythropoiesis stimulating agent (ESA) therapy and percentage change in Hb levels from baseline to the end of the study were analyzed. RESULTS: The mean Hb levels of postESA therapy increased significantly compared with those of preESA therapy in both ESA regimens. The percentage increase in Hb levels and erythropoietin resistance index did not show a significant difference between the different ESA regimens. No difference was observed between the regimens regarding mean Hb levels after ESA therapy. Additionally, there were no serious adverse effects leading to withdrawal from treatment. CONCLUSION: Biweekly high doses of EPO-alpha therapy may be equally as effective as Q2W DA-alpha therapy in maintaining target Hb levels in non-dialysis CKD patients. PMID- 26885481 TI - Toxic epidermal necrolysis associated with deflazacort therapy with nephrotic syndrome. AB - Toxic epidermal necrolysis (TEN) is a drug-related fatal disease. Extensive necrosis of the epidermis can lead to serious complications. This report describes two cases of TEN, associated with deflazacort (DFZ), in two boys, aged 4 years and 14 years, with nephrotic syndrome (NS). The 14-year-old male teenager received DFZ following NS relapse. After 17 days, pruritic papules appeared on the lower extremities. Another case involved a 4-year-old boy receiving DFZ and enalapril. After a 41-day DFZ treatment period, erythematous papules appeared on the palms and soles. Within 3 days, both boys developed widespread skin lesions (>50%) and were admitted to the intensive care unit for resuscitative and supportive treatment. The patients showed improvement after intravenous immunoglobulin-G therapy. Owing to the rapid, fatal course of TEN, clinicians need to be aware of the adverse effects of this drug when treating cases of NS. PMID- 26885480 TI - Ipsilateral leg swelling after renal transplantation as an alarming sign of Iliac vein stenosis. AB - Iliac vein stenosis is a rare vascular complication of renal transplantation that may compromise allograft function if not recognized and corrected in a timely fashion. Because chronic venous stenosis may remain undiagnosed for several years, a high index of suspicion should be maintained until diagnosing this rare disease. A 56-year-old renal transplant recipient presented with unilateral leg swelling and renal dysfunction 16 years after transplantation. Computed tomography excluded deep vein thrombosis and revealed tight iliac vein stenosis on the side of the renal transplant. Following angiographic confirmation of the stenosis, endovascular treatment was successfully performed with a purposefully designed, self-expanding, venous stent. Ipsilateral leg swelling is an alarming sign for the diagnosis of iliac vein stenosis after renal transplantation. Percutaneous intervention with venous stent placement seems to be a safe and effective treatment of this rare condition. PMID- 26885482 TI - Resolution of uremic tumoral calcinosis in a patient on peritoneal dialysis with long-term low-calcium dialysate treatment. AB - Tumoral calcinosis is a rare complication in uremic patients. An in-depth review of published literature suggests that most patients with uremic tumoral calcinosis do not respond to medical treatment. Here, we report the case of a patient on peritoneal dialysis who presented with infected multifocal masses on both hip joints and was successfully treated by medical intervention. The patient was diagnosed with uremic tumoral calcinosis by physical examination and radiologic imaging, and treated with low-calcium dialysis and a non-calcium phosphate binder, sevelamer, without increasing the dose of dialysis. At the 36 month follow-up, the majority of masses had disappeared and the patient was asymptomatic. PMID- 26885484 TI - Association between mortality and abdominal aortic calcification and their progression in hemodialysis patients. PMID- 26885483 TI - A case of primary aldosteronism combined with acquired nephrogenic diabetes insipidus. AB - Aldosterone-producing adrenal adenoma can induce various clinical manifestations as a result of chronic exposure to aldosterone. We report a rare case of a 37 year-old man who complained of general weakness and polyuria. He was diagnosed with aldosterone-producing adrenal adenoma and nephrogenic diabetes insipidus. Aldosterone enhances the secretion of potassium in the collecting duct, which can lead to hypokalemia. By contrast, nephrogenic diabetes insipidus, which manifests as polyuria and polydipsia, can occur in several clinical conditions such as acquired tubular disease and those attributed to toxins and congenital causes. Among them, hypokalemia can also damage tubular structures in response to vasopressin. The patient's urine output was >3 L/d and was diluted. Owing to the ineffectiveness of vasopressin, we eventually made a diagnosis of nephrogenic diabetes insipidus. Laparoscopic adrenalectomy and intraoperative kidney biopsy were subsequently performed. The pathologic finding of kidney biopsy revealed a decrease in aquaporin-2 on immunohistochemical stain. PMID- 26885485 TI - Youyou Tu: significance of winning the 2015 Nobel Prize in Physiology or Medicine. AB - Youyou Tu, a female scientist at the China Academy of Traditional Chinese Medicine in Beijing, is the first Chinese winner of the Nobel Prize in Physiology or Medicine. Based on the study of recipes which had been used for thousands of years to treat fever, Tu's group discovered that the plant artemesia annua, sweet wormwood, showed substantial inhibition of rodent malaria parasites. Her achievement and experience have inspired other researchers and emphasized the development of traditional Chinese medicine. Her award has led to a heated discussion about scientific research investment, fair treatment of research staff, and intellectual property right (IPR) protection in China. PMID- 26885486 TI - Safety of anticoagulation with uninterrupted warfarin vs. interrupted dabigatran in patients requiring an implantable cardiac device. AB - BACKGROUND: The optimal strategy of peri-procedural anticoagulation in patients undergoing permanent cardiac device implantation is controversial. Our objective was to compare the major bleeding and thromboembolic complications in patients managed with uninterrupted warfarin (UW) vs. interrupted dabigatran (ID) during permanent pacemaker (PPM) or implantable cardioverter defibrillators (ICD) implantation. METHODS: A retrospective cohort study of all eligible patients from July 2011 through January 2012 was performed. UW was defined as patients who had maintained a therapeutic international normalized ratio (INR) on the day of the procedure. ID was defined as stopping dabigatran >=12 hours prior to the procedure and then resuming after implantation. Major bleeding events included hemothorax, hemopericardium, intracranial hemorrhage, gastrointestinal bleed, epistaxis, or pocket hematoma requiring surgical intervention. Thromboembolic complications included stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or arterial embolism. RESULTS: Of the 133 patients (73.4+/ 11.0 years; 91 males) in the study, 86 received UW and 47 received ID. One (1.2%) patient in the UW group sustained hemopericardium perioperatively and died. In comparison, the ID patients had no complications. As compared to the ID group, the UW group had a higher median CHADS2 score (2 vs. 3, P=0.04) and incidence of Grade 1 pocket hematoma (0% vs. 7%, P=0.09). Neither group developed any thromboembolic complications. CONCLUSIONS: Major bleeding rates were similar among UW and ID groups. Perioperative ID appears to be a safe anticoagulation strategy for patients undergoing PPM or ICD implantation. PMID- 26885487 TI - Spectrum of heart diseases in children: an echocardiographic study of 1,666 subjects in a pediatric hospital, Yaounde, Cameroon. AB - BACKGROUND: Children's health programs in Sub-Saharan Africa have always been oriented primarily to infectious diseases and malnutrition. We are witnessing in the early 21(st) century an epidemiological transition marked by the decline of old diseases and the identification of new diseases including heart disease. Therefore, it is necessary to describe the spectrum of these diseases in order to better prepare health workers to these new challenges. METHODS: We conducted a cross-sectional study focused on heart disease diagnosed by echocardiography in children seen from January 2006 to December 2014 in a pediatric hospital of Yaounde. We collected socio-demographic data and the types of heart disease from registers, patients files as well as the electronic database of echocardiographic records. RESULTS: A total of 2,235 patients underwent echocardiographic examination during the study period including 1,666 subjects with heart disease. Congenital cardiopathies were found in 1,230 (73.8%) patients and acquired abnormalities in 429 (25.8%). Seven children (0.4%) had a combination of both types. Congenital heart defects (CHD) were dominated by ventricular septal defect (VSD). Acquired heart disease was mostly rheumatic valvulopathies. Dyspnea on exertion was the most frequent presenting complaint (87.6%). Discovery of a heart murmur was the principal clinical finding on physical examination (81.4%). The median age was 9 months for congenital heart disease and 132 months for acquired heart disease. CONCLUSIONS: As infectious diseases recede and the diagnostic facilities are improving, pediatric heart diseases occupy a more important position in the spectrum of pediatric diseases in our context. However, the ability to evoke the diagnosis remains unsatisfactory by the majority of health personnel and therefore needs to be improved. Apart from congenital heart diseases, the impact of acquired heart diseases, rheumatic valvulopathy being the highest ranking, is remarkable in pediatrics. Awareness of health personnel for better management of child tonsillitis is more than ever a necessity. This preventive attitude of rheumatic heart disease is the main attitude available in our disadvantaged economic environment. PMID- 26885488 TI - Percutaneous transvenous mitral commissurotomy in juvenile mitral stenosis. AB - BACKGROUND: Percutaneous transvenous mitral commissurotomy (PTMC) is a valid alternative to surgical therapy in selected patients with mitral stenosis. Juvenile mitral stenosis (JMS) varies uniquely from adult rheumatic heart disease (RHD). We aimed to evaluate the efficacy of PTMC in JMS patients. METHODS: It was a single centre, retrospective study conducted between July 2013 to June 2015 in Shahid Gangalal National Heart Centre, Kathmandu, Nepal. Medical records of all consecutive patients aged less than 21 years who underwent PTMC were included. Mitral valve area (MVA), left atrial pressure and mitral regurgitation (MR) were compared pre and post procedure. RESULTS: During the study period 131 JMS patients underwent PTMC. Seventy (53.4%) were female and 61 (46.6%) were male. Among the 131 patients, 40 (30.5%) patients were below the age of 15 years. Patient age ranged between 9 to 20 years with the mean of 16.3+/-2.9 years. Electrocardiography (ECG) findings were normal sinus rhythm in 115 (87.7%) patients and atrial fibrillation in 16 (12.3%) patients. Left atrial size ranged from 2.9 to 6.1 cm with the mean of 4.5+/-0.6 cm. The mean MVA increased from 0.8+/-0.1 cm(2) to 1.6+/-0.2 following PTMC. Mean left atrial pressure decreased from their pre-PTMC state of 27.5+/-8.6 to 14.1+/-5.8 mmHg. Successful results were observed in 115 (87.7%) patients. Suboptimal MVA <1.5 cm(2) in 11 (8.4%) patients and post-procedure MR of more than moderate MR in 5 (3.8%) patients was the reason for unsuccessful PTMC. CONCLUSIONS: PTMC in JMS is safe and effective. PMID- 26885489 TI - Anatomic distribution of culprit lesions in patients with non-ST-segment elevation myocardial infarction and normal ECG. AB - BACKGROUND: In patients presenting with non-ST-elevation myocardial infarction (NSTEMI), left anterior descending (LAD) coronary artery and three-vessel disease are the most commonly encountered culprit lesions in the presence of ST depression, while one third of patients with left circumflex (LCX) artery related infarction have normal ECG. We sought to determine the predictors of presence of culprit lesion in NSTEMI patients based on ECG, echocardiographic, and clinical characteristics. METHODS: Patients admitted to the coronary care unit with the diagnosis of NSTEMI between June 2012 and December 2013 were retrospectively identified. Admission ECG was interpreted by an electrophysiologist that was blinded to the result of the coronary angiogram. Patients were dichotomized into either normal or abnormal ECG group. The primary endpoint was presence of culprit lesion. Secondary endpoints included length of stay, re-hospitalization within 60 days, and in-hospital mortality. RESULTS: A total of 118 patients that were identified; 47 with normal and 71 with abnormal ECG. At least one culprit lesion was identified in 101 patients (86%), and significantly more among those with abnormal ECG (91.5% vs. 76.6%, P=0.041).The LAD was the most frequently detected culprit lesion in both groups. There was a higher incidence of two and three vessel disease in the abnormal ECG group (P=0.041).On the other hand, there was a trend of higher LCX involvement (25% vs. 13.8%, P=0.18) and more normal coronary arteries in the normal ECG group (23.4% vs. 8.5%, P=0.041). On multivariate analysis, prior history of coronary artery disease (CAD) [odds ratio (OR) 6.4 (0.8-52)], male gender [OR 5.0 (1.5-17)], and abnormal admission ECG [OR 3.6 (1.12-12)], were independent predictors of a culprit lesion. There was no difference in secondary endpoints between those with normal and abnormal ECG. CONCLUSIONS: Among patients presenting with NSTEMI, prior history of CAD, male gender and abnormal admission ECG were independent predictors of a culprit lesion. An abnormal ECG was significantly associated with two and three-vessel disease, while normal ECG was more associated with LCX involvement or normal angiogram. Admission ECG did not impact secondary outcomes. PMID- 26885490 TI - HDL function and subclinical atherosclerosis in juvenile idiopathic arthritis. AB - BACKGROUND: Increasing evidence suggests that inflammation adversely impacts the protective properties of high-density lipoproteins (HDL) and progression of atherosclerosis. The impact of early chronic inflammatory conditions on HDL function and vascular risk has not been well investigated. METHODS: We compared measures of HDL particle distribution and functionality, in addition to measures of carotid intima-medial thickness (cIMT) in patients with juvenile idiopathic arthritis (JIA) and age matched controls. RESULTS: JIA patients demonstrated lower levels of HDL cholesterol [47.0 (40.0, 56.0) vs. 56.0 (53.0, 61.0) mg/dL, P=0.04], total HDL [29.5 (27.9, 32.3) vs. 32.9 (31.6, 36.3) mg/dL, P=0.05] and large HDL [5.1 (3.7, 7.3) vs. 8.0 (6.7, 9.7) mg/dL, P=0.04] particles. In association JIA patients demonstrated greater cholesterol efflux mediated via ATP binding cassette A1 (ABCA1) [17.3% (12.8, 19.7) vs. 10.0% (5.8, 16.0), P=0.05] and less efflux mediated via ATP binding cassette G-1 (ABCG1) [3.2% (2.0, 3.9) vs. 4.8% (3.5, 5.8), P=0.01] and SR-B1 [6.9% (6.0, 8.4) vs. 9.1% (8.6, 10.2), P=0.002] compared with controls. Exposure of macrophages to serum from JIA patients resulted in a smaller increase in mRNA expression of ABCA1 (2.0+/-0.95 vs. 7.1+/-5.7 fold increase, P=0.01) and greater increases in expression of ABCG1 [1.4 (0.9, 1.5) vs. 0.8 (0.7, 1.1) fold increase, P=0.04] and SR-B1 (1.3+/-0.47 vs. 0.7+/-0.3 fold increase, P=0.001) compared with controls. Arylesterase (128.9+/-27.6 vs. 152.0+/-45.2 umoles/min/mL, P=0.04) activity and endothelial cell migration (491.2+/-68.9 vs. 634.2+/-227.4 cells/field, P=0.01) were less in JIA patients. No differences in cIMT were observed between JIA patients and controls. CONCLUSIONS: The presence of JIA was associated with alterations in HDL particle distribution, cholesterol efflux and non-lipid transporting activities. The ultimate implication of these findings for cardiovascular risk requires further investigation. PMID- 26885491 TI - Evaluation of fetal echocardiography as a routine antenatal screening tool for detection of congenital heart disease. AB - BACKGROUND: Fetal echocardiography plays a pivotal role in identifying the congenital heart defects (CHDs) in utero. Though foetal echocardiography is mostly reserved for high risk pregnant women, its role as a routine prenatal screening tool still needs to be defined. Performing foetal echocardiography based on only these indications can lead to a significant numbers of CHD cases going undetected who will be deprived of further management leading to increased early neonatal mortalities. The aim of this study is to assess the incidence of CHDs by fetal echocardiography in an unselected population of pregnant women in comparison with pregnant women with conventional high risk factors for CHD. METHODS: This study enrolled consecutive pregnant women who attended antenatal clinic between 2008 and 2012 in a tertiary care hospital. These pregnant women were categorized into two groups: high risk group included pregnant women with traditional risk factors for CHD as laid down by Pediatric Council of the American Society of Echocardiography and low risk group. Detailed fetal 2 D echocardiography was done. RESULTS: A total of 1,280 pregnant women were included in study. The 118 women were categorized as the high risk group while remaining 1,162 were included in the low risk group. Twenty six cases of CHDs were detected based on abnormal foetal echocardiography (20.3 per 1,000). Two of the 26 cases of CHD occurred in high risk group whereas the remaining 24 occurred in low risk pregnancy. The difference in the incidence of CHDs between the two groups was not significant statistically (P=0.76). CONCLUSIONS: Our study shows no difference in incidence of CHDs between pregnancies associated with high risk factors compared to low risk pregnancies. So we advocate foetal echocardiography should be included as a part of routine antenatal screening and all pregnant women irrespective of risk factors for CHDs. PMID- 26885493 TI - Coronary heart disease in sub-Saharan Africa: still rare, misdiagnosed or underdiagnosed? AB - Coronary heart disease (CHD) is the leading cause of death in developed countries, but it has generally been considered to be rare in sub-Saharan Africa (SSA). SSA is undergoing rapid epidemiological transition with an increasing prevalence of major cardiovascular risk factors and consequential cardiovascular diseases such as stroke. However, CHD including myocardial infarction has generally been considered to be rare despite this deterioration in the risk factors profile. There is an urgent need to raise awareness about CHD both in the general population and healthcare professionals while making available simple, inexpensive screening and diagnostic tools in sub-Saharan African countries. PMID- 26885494 TI - Cardiovascular diseases in Ghana within the context of globalization. AB - This paper discusses how globalization and its elements are influencing health dynamics and in particular Cardiovascular diseases (CVDs) in Ghana. It assesses the growing burden of CVDs and its relationship with globalization. It further describes the conceptual framework on which to view the impact of globalization on CVDs in Ghana. It also set out the dimensions of the relationship between CVD risk factors and globalization. The paper concludes with a discussion on strategies for tackling the growing burden of CVDs in Ghana. PMID- 26885492 TI - Cardiac sarcoidosis-state of the art review. AB - Sarcoidosis is a multi-system inflammatory disorder of unknown etiology resulting in formation of non-caseating granulomas. Cardiac involvement-which is associated with worse prognosis-has been detected in approximately 25% of individuals based on autopsy or cardiac imaging studies. Nevertheless, the diagnosis of cardiac sarcoidosis is challenging due to the low yield of endomyocardial biopsy, and the limited accuracy of various clinical criteria. Thus, no gold standard diagnostic criterion exists. This review will summarize the pathophysiology, diagnosis, and treatment of cardiac sarcoidosis with a focus on advanced cardiovascular imaging, We review the evidence to support a role for cardiac magnetic resonance (CMR) imaging in the initial evaluation of selected patients with suspected cardiac sarcoidosis, with cardiac positron emission tomography (PET) as an alternative or complementary initial diagnostic test in a subgroup of patients in whom CMR may be contra-indicated or when CMR is negative with continued clinical concern for myocardial inflammation. In addition to the diagnostic value of these tests, CMR and PET are also useful in identifying patients who have higher risk of adverse events such as ventricular tachycardia or death, in whom preventive therapies such as defibrillators should be more strongly considered. Although no randomized controlled trials for treatment of cardiac sarcoidosis exist, immunosuppressive therapy is often used. We review emerging evidence regarding the use of cardiac PET to identify and quantity the amount of myocardial inflammation as well as to guide the use of immunotherapy. Future studies are needed to determine the benefit of imaging guided therapies aimed at improving patient outcomes. PMID- 26885495 TI - Cardiac magnetic resonance imaging for myocardial perfusion and diastolic function-reference control values for women. AB - Angina, heart failure with preserved ejection fraction (HFpEF) and coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD) are more common in women and are associated with adverse cardiovascular prognosis. Cardiac magnetic resonance imaging (CMRI) is established for assessment of left ventricular (LV) morphology and systolic function and is increasingly used to assess myocardial perfusion and diastolic function. Indeed, stress CMRI allows measurement of myocardial perfusion reserve index (MPRI) using semi-quantitative techniques, and quantification of LV volumetric filling patterns provides valuable insight into LV diastolic function. The utility of these two techniques remains limited, because reference control values for MPRI and LV diastolic function in asymptomatic middle-aged, women have not previously been established. To address this limitation, we recruited twenty women, without clinical cardiovascular disease or cardiovascular risk factors, with normal maximal Bruce protocol exercise treadmill testing. Subjects underwent CMRI (1.5 tesla) using a standardized protocol of adenosine stress and rest perfusion and LV cinematic imaging. Commercially available with automated CMRI segmentation was used for calculation of MPRI, LV filling profiles, and ejection fraction. Mean age was 54+/-9 years and mean body mass index was 25+/-4 kg/m(3). The exercise treadmill testing results demonstrated a normotensive group with normal functional capacity and hemodynamic response. We report reference control values for semi-quantitative MPRI as well as measures of LV systolic and diastolic function including ejection fraction, stroke volume, peak filling rate (PFR), PFR adjusted for end-diastolic volume (EDV) and stroke volume, time to PFR, and EDV index. The data herein provide reference values for MPRI and diastolic function in a cohort of healthy, middle-aged of women. These reference values may be used for comparison with a variety of patient populations, including women with CMD and HFpEF. PMID- 26885496 TI - Direct communication between the left circumflex and the right coronary arteries: a very rare coronary anomaly circulation. AB - Coronary artery anomalies (CAA) are congenital changes in their origin, course, and/or structure. Intercoronary communication (ICC) is a very rare subset with uni- or bidirectional blood flow between two or more coronary arteries. We present the case of a 58-year-old man with an acute coronary syndrome whose coronary angiography incidentally showed a surprising and very rare communication between the right coronary and left circumflex arteries. PMID- 26885498 TI - Chrysanthemums in full bloom. PMID- 26885497 TI - Prof. Brian Griffin: radiation heart disease. PMID- 26885499 TI - Bridging the Gap, Facing the Challenge-the 26(th) Great Wall International Congress of Cardiology (GW-ICC). AB - The joint venue of the 26(th) Great Wall International Congress of Cardiology (GW ICC) & Asia Pacific Heart Congress 2015 (APHC 2015) & International Congress Cardiovascular Prevention and Rehabilitation 2015 (ICCPR 2015) were held from October 29 to November 01, 2015 at the China National Convention Center (CNCC), Beijing, China. This year's conference focused on cardiovascular disease prevention, health promotion, education and training, as well as disease management and rehabilitation. PMID- 26885501 TI - Acupuncture for Erectile Dysfunction: A Systematic Review. AB - BACKGROUND: Acupuncture is increasingly used to treat patients with erectile dysfunction (ED), and our systematic review aimed to evaluate the current evidence for the efficacy and safety of acupuncture in treating ED. METHODS: An electronic search was conducted in eight databases to identify randomized controlled trials (RCTs) of acupuncture for treating erectile dysfunction that were published in English and Chinese. The Cochrane Risk of Bias tool was used to assess the risk of bias. RESULTS: Three RCTs with a total of 183 participants met the inclusion criteria. One trial showed the beneficial effects of acupuncture compared with sham acupuncture while the others did not. One trial suggested that acupuncture combined with psychological therapy was superior to psychological therapy alone. However, the overall methodological and reporting quality of the studies was low. The safety of acupuncture for ED was unclear because there were too few reports on this topic. CONCLUSION: The available evidence supporting that acupuncture alone improves ED was insufficient and the available studies failed to show the specific therapeutic effect of acupuncture. Future well-designed and rigorous RCTs with a large sample size are required. This trial is registered with CRD42014013575. PMID- 26885502 TI - Experimental Heart Failure Models and Their Pathophysiological Characterization. PMID- 26885500 TI - Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment. AB - Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFbeta1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI. PMID- 26885503 TI - Organogenesis and Ultrastructural Features of In Vitro Grown Canna indica L. AB - An efficient protocol for micropropagation of Canna indica L., an economically and pharmaceutically important plant, was standardized using rhizome explants, excised from two-month-old aseptic seedlings. Complete plant regeneration was induced on MS medium supplemented with 3.0 mg/L BAP plus 1.5 mg/L NAA, which produced the highest number of shoots (73.3 +/- 0.5%) and roots (86.7 +/- 0.4%) after 2 weeks. Furthermore, the optimum media for multiple shoots regeneration were recorded on MS enriched with 7.0 mg/L BAP (33.0 +/- 0.5%). Plantlets obtained were transplanted to pots after two months and acclimatized in the greenhouse, with 75% survival. In addition, ultrastructural studies showed that rhizomes of in vitro grown specimens were underdeveloped compared to the in vivo specimens, possibly due to the presence of wide spaces. Meanwhile, the leaves of in vivo specimens had more open stomata compared to in vitro specimens, yet their paracytic stomata structures were similar. Hence, there were no abnormalities or major differences between in vitro regenerants and mother plants. PMID- 26885504 TI - Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis. AB - Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms. PMID- 26885505 TI - The Subcellular Localization and Functional Analysis of Fibrillarin2, a Nucleolar Protein in Nicotiana benthamiana. AB - Nucleolar proteins play important roles in plant cytology, growth, and development. Fibrillarin2 is a nucleolar protein of Nicotiana benthamiana (N. benthamiana). Its cDNA was amplified by RT-PCR and inserted into expression vector pEarley101 labeled with yellow fluorescent protein (YFP). The fusion protein was localized in the nucleolus and Cajal body of leaf epidermal cells of N. benthamiana. The N. benthamiana fibrillarin2 (NbFib2) protein has three functional domains (i.e., glycine and arginine rich domain, RNA-binding domain, and alpha-helical domain) and a nuclear localization signal (NLS) in C-terminal. The protein 3D structure analysis predicted that NbFib2 is an alpha/beta protein. In addition, the virus induced gene silencing (VIGS) approach was used to determine the function of NbFib2. Our results showed that symptoms including growth retardation, organ deformation, chlorosis, and necrosis appeared in NbFib2 silenced N. benthamiana. PMID- 26885507 TI - Preparation of Microencapsulated Bacillus subtilis SL-13 Seed Coating Agents and Their Effects on the Growth of Cotton Seedlings. AB - Inoculation of the bacterial cells of microbial seed coating agents (SCAs) into the environment may result in limited survival and colonization. Therefore, the application efficacy of an encapsulated microbial seed coating agent (ESCA) was investigated on potted cotton plants; the agent was prepared with polyvinyl alcohol, sodium dodecyl sulfate, bentonite, and microencapsulated Bacillus subtilis SL-13. Scanning electron micrography revealed that the microcapsules were attached to ESCA membranes. The ESCA film was uniform, bubble-free, and easy to peel. The bacterial contents of seeds coated with each ESCA treatment reached 10(6) cfu/seed. Results indicated that the germination rate of cotton seeds treated with ESCA4 (1.0% (w/v) sodium alginate, 4.0% polyvinyl alcohol, 1.0% sodium dodecyl sulfate, 0.6% acacia, 0.5% bentonite, and 10% (v/v) microcapsules) increased by 28.74%. Other growth factors of the cotton seedlings, such as plant height, root length, whole plant fresh weight, and whole plant dry weight, increased by 52.70%, 25.13%, 46.47%, and 33.21%, respectively. Further analysis demonstrated that the peroxidase and superoxide dismutase activities of cotton seedlings improved, whereas their malondialdehyde contents decreased. Therefore, the ESCA can efficiently improve seed germination, root length, and growth. The proposed ESCA exhibits great potential as an alternative to traditional SCA in future agricultural applications. PMID- 26885509 TI - The Development and Validation of a Rapid Assessment Tool of Primary Care in China. AB - Introduction. With Chinese health care reform increasingly emphasizing the importance of primary care, the need for a tool to evaluate primary care performance and service delivery is clear. This study presents a methodology for a rapid assessment of primary care organizations and service delivery in China. Methods. The study translated and adapted the Primary Care Assessment Tool-Adult Edition (PCAT-AE) into a Chinese version to measure core dimensions of primary care, namely, first contact, continuity, comprehensiveness, and coordination. A cross-sectional survey was conducted to assess the validity and reliability of the Chinese Rapid Primary Care Assessment Tool (CR-PCAT). Eight community health centers in Guangdong province have been selected to participate in the survey. Results. A total of 1465 effective samples were included for data analysis. Eight items were eliminated following principal component analysis and reliability testing. The principal component analysis extracted five multiple-item scales (first contact utilization, first contact accessibility, ongoing care, comprehensiveness, and coordination). The tests of scaling assumptions were basically met. Conclusion. The standard psychometric evaluation indicates that the scales have achieved relatively good reliability and validity. The CR-PCAT provides a rapid and reliable measure of four core dimensions of primary care, which could be applied in various scenarios. PMID- 26885508 TI - Immunohistochemical Studies on Galectin Expression in Colectomised Patients with Ulcerative Colitis. AB - INTRODUCTION: The aetiology and pathogenesis of ulcerative colitis (UC) are essentially unknown. Galectins are carbohydrate-binding lectins involved in a large number of physiological and pathophysiological processes. Little is known about the role of galectins in human UC. In this immunohistochemical exploratory study, both epithelial and inflammatory cell galectin expression were studied in patients with a thoroughly documented clinical history and were correlated with inflammatory activity. MATERIAL AND METHODS: Surgical whole intestinal wall colon specimens from UC patients (n = 22) and controls (n = 10) were studied. Clinical history, pharmacological treatment, and modified Mayo-score were recorded. Tissue inflammation was graded, and sections were stained with antibodies recognizing galectin-1, galectin-2, galectin-3, and galectin-4. RESULTS: Galectin-1 was undetectable in normal and UC colonic epithelium, while galectin-2, galectin-3, and galectin-4 were strongly expressed. A tendency towards diminished epithelial expression with increased inflammatory grade for galectin-2, galectin-3, and galectin-4 was also found. In the inflammatory cells, a strong expression of galectin-2 and a weak expression of galectin-3 were seen. No clear-cut correlation between epithelial galectin expression and severity of the disease was found. CONCLUSION: Galectin expression in patients with UC seems to be more dependent on disease focality and individual variation than on degree of tissue inflammation. PMID- 26885510 TI - The Role of a Primary Arthroplasty in the Treatment of Proximal Tibia Fractures in Orthogeriatric Patients. AB - The total knee arthroplasty (TKA) is the gold standard for patients with an advanced symptomatic gonarthrosis. However, there are very few publications dealing with the primary TKA for patients with a proximal tibia fracture. In our retrospective study we evaluated 30 patients treated with a TKA for a proximal tibia fracture in our institution between 01/2008 and 12/2014. We collected the following statistical data from each patient: age, classification of the fracture (AO-classification), type of prosthesis used, length of the operation and hospitalization, and complications during the follow-up. We used the Knee Society Score (KSS) and the WOMAC score to evaluate the function. The Knee Society Score showed an average "general knee score" (KSS1) of 81.1 points and an average "functional knee score" (KSS2) of 74.5 points. The average WOMAC score was 78.6 points. Immediate postoperative mobilization with the possibility of a full weight bearing is of crucial importance for the geriatric patients to maintain the mobility they had prior to the operation and reduce medical complications. Because of these advantages, the primary TKA seems to be a promising alternative to the ORIF of a proximal tibia fracture in the orthogeriatric patient. PMID- 26885506 TI - New Ti-Alloys and Surface Modifications to Improve the Mechanical Properties and the Biological Response to Orthopedic and Dental Implants: A Review. AB - Titanium implants are widely used in the orthopedic and dentistry fields for many decades, for joint arthroplasties, spinal and maxillofacial reconstructions, and dental prostheses. However, despite the quite satisfactory survival rates failures still exist. New Ti-alloys and surface treatments have been developed, in an attempt to overcome those failures. This review provides information about new Ti-alloys that provide better mechanical properties to the implants, such as superelasticity, mechanical strength, and corrosion resistance. Furthermore, in vitro and in vivo studies, which investigate the biocompatibility and cytotoxicity of these new biomaterials, are introduced. In addition, data regarding the bioactivity of new surface treatments and surface topographies on Ti-implants is provided. The aim of this paper is to discuss the current trends, advantages, and disadvantages of new titanium-based biomaterials, fabricated to enhance the quality of life of many patients around the world. PMID- 26885512 TI - Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats. AB - Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 MUg/kg/day MeHg, (3) 500 MUg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined. PMID- 26885511 TI - Effectiveness of the Virtual Reality System Toyra on Upper Limb Function in People with Tetraplegia: A Pilot Randomized Clinical Trial. AB - The aim of this study was to investigate the effects of a virtual reality program combined with conventional therapy in upper limb function in people with tetraplegia and to provide data about patients' satisfaction with the virtual reality system. Thirty-one people with subacute complete cervical tetraplegia participated in the study. Experimental group received 15 sessions with Toyra((r)) virtual reality system for 5 weeks, 30 minutes/day, 3 days/week in addition to conventional therapy, while control group only received conventional therapy. All patients were assessed at baseline, after intervention, and at three month follow-up with a battery of clinical, functional, and satisfaction scales. Control group showed significant improvements in the manual muscle test (p = 0,043, partial eta (2) = 0,22) in the follow-up evaluation. Both groups demonstrated clinical, but nonsignificant, changes to their arm function in 4 of the 5 scales used. All patients showed a high level of satisfaction with the virtual reality system. This study showed that virtual reality added to conventional therapy produces similar results in upper limb function compared to only conventional therapy. Moreover, the gaming aspects incorporated in conventional rehabilitation appear to produce high motivation during execution of the assigned tasks. This trial is registered with EudraCT number 2015-002157-35. PMID- 26885513 TI - Volumetric Modulated Arc Therapy for Spine Radiosurgery: Superior Treatment Planning and Delivery Compared to Static Beam Intensity Modulated Radiotherapy. AB - PURPOSE: Spine stereotactic radiosurgery (SRS) delivers an accurate and efficient high radiation dose to vertebral metastases in 1-5 fractions. We aimed to compare volumetric modulated arc therapy (VMAT) to static beam intensity modulated radiotherapy (IMRT) for spine SRS. METHODS AND MATERIALS: Ten spine lesions of previously treated SRS patients were planned retrospectively using both IMRT and VMAT with a prescribed dose of 16 Gy to 100% of the planning target volume (PTV). The plans were compared for conformity, homogeneity, treatment delivery time, and safety (spinal cord dose). RESULTS: All evaluated parameters favored the VMAT plan over the IMRT plans. D min in the IMRT was significantly lower than in the VMAT plan (7.65 Gy/10.88 Gy, p < 0.001), the Dice Similarity Coefficient (DSC) was found to be significantly better for the VMAT plans compared to the IMRT plans (0.77/0.58, resp., p value < 0.01), and an almost 50% reduction in the net treatment time was calculated for the VMAT compared to the IMRT plans (6.73 min/12.96 min, p < 0.001). CONCLUSIONS: In our report, VMAT provides better conformity, homogeneity, and safety profile. The shorter treatment time is a major advantage and not only provides convenience to the painful patient but also contributes to the precision of this high dose radiation therapy. PMID- 26885514 TI - An In Vitro Comparison of PMMA and Calcium Sulfate as Carriers for the Local Delivery of Gallium(III) Nitrate to Staphylococcal Infected Surgical Sites. AB - Antibiotic-loaded bone cements, including poly(methyl methacrylate) (PMMA) and calcium sulfate (CaSO4), are often used for treatment of orthopaedic infections involving Staphylococcus spp., although the effectiveness of this treatment modality may be limited due to the emergence of antimicrobial resistance and/or the development of biofilms within surgical sites. Gallium(III) is an iron analog capable of inhibiting essential iron-dependent pathways, exerting broad antimicrobial activity against multiple microorganisms, including Staphylococcus spp. Herein, we evaluated PMMA and CaSO4 as carriers for delivery of gallium(III) nitrate (Ga(NO3)3) to infected surgical sites by assessing the release kinetics subsequent to incorporation and antimicrobial activity against S. aureus and S. epidermidis. PMMA and to a lesser extent CaSO4 were observed to be compatible as carriers for Ga(NO3)3, eluting concentrations with antimicrobial activity against planktonic bacteria, inhibiting bacterial growth, and preventing bacterial colonization of beads, and effective against established bacterial biofilms of S. aureus and S. epidermidis. Collectively, our in vitro results indicate that PMMA is a more suitable carrier compared to CaSO4 for delivery of Ga(NO3)3; moreover they provide evidence for the potential use of Ga(NO3)3 with PMMA as a strategy for the prevention and/or treatment for orthopaedic infections. PMID- 26885515 TI - The Superficial Stromal Scar Formation Mechanism in Keratoconus: A Study Using Laser Scanning In Vivo Confocal Microscopy. AB - To investigate the mechanism of superficial stromal scarring in advanced keratoconus using confocal microscopy, the keratocyte density, distribution, micromorphology of corneal stroma, and SNP in three groups were observed. Eight corneal buttons of advanced keratoconus were examined by immunohistochemistry. The keratocyte densities in the sub-Bowman's stroma, anterior stroma, and posterior stroma and the mean SNP density were significantly different among the three groups. In the mild-to-moderate keratoconus group, activated keratocyte nuclei and comparatively highly reflective ECM were seen in the sub-Bowman's stroma, while fibrotic structures with comparatively high reflection were visible in the anterior stroma in advanced keratoconus. The alternating dark and light bands in the anterior stroma of the mild-to-moderate keratoconus group showed great variability in width and direction. The wide bands were localized mostly in the posterior stroma that corresponded to the Vogt striae in keratoconus and involved the anterior stroma only in advanced keratoconus. Histopathologically, high immunogenicity of alpha-SMA, vimentin, and FAP was expressed in the region of superficial stromal scarring. In vivo confocal microscopy revealed microstructural changes in the keratoconic cone. The activation of superficial keratocytes and abnormal remodeling of ECM may both play a key role in the superficial stromal scar formation in advanced keratoconus. PMID- 26885517 TI - Electrocardiography as the First Step for the Further Examination of Cardiac Involvement in Myasthenia Gravis. AB - INTRODUCTION: Cardiac involvement of myasthenia gravis (MG) accompanies a poor prognosis. In the present study, we aimed to investigate the relationship between ECG abnormality and cardiac involvement. METHODS: Of 178 patients diagnosed with MG between 2001 and 2013 at our hospital, we retrospectively analyzed consecutive 58 patients who underwent both ECG and echocardiography and without underlying cardiovascular disease. ECG abnormalities were defined by computer-assigned Minnesota-codes. Cardiac damage was defined as either (1) ejection fraction (EF) <55% on echocardiography or (2) elevated E/e', the ratio of mitral velocity to early diastolic velocity of the mitral annulus >8 on echocardiography. RESULTS: Thirty-three patients (56.8%) had ECG abnormality. An elevated E/e' was observed in patients with ECG abnormality compared to those without ECG abnormality (11.2 +/- 3.2, 8.7 +/- 2.2, resp., p = 0.03). Among patients with ECG abnormality, 14 of 15 patients showed cardiac damage. Among patients without ECG abnormality, 6 of 33 patients showed cardiac damage (p = 0.003). Reduced EF was observed in five patients (8.6%) with ECG abnormality and none in patients without ECG abnormality. CONCLUSIONS: ECG may aid as the first step for the further examination of cardiac damage in patients with MG. PMID- 26885516 TI - Identification of Novel RD1 Antigens and Their Combinations for Diagnosis of Sputum Smear-/Culture+ TB Patients. AB - Rapid and accurate diagnosis of pulmonary tuberculosis (PTB) is an unresolved problem worldwide, especially for sputum smear- (S-) cases. In this study, five antigen genes including Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 were cloned from Mycobacterium tuberculosis (Mtb) RD1 and overexpressed to generate antigen fragments. These antigens and their combinations were investigated for PTB serodiagnosis. 298 serum samples were collected from active PTB patients, including 117 sputum smear+ (S+) and sputum culture+ (C+) cases, 101 S-/C+ cases, and 80 S-/C- cases. The serum IgG levels of the five antigens were measured by ELISA. Based on IgG levels, the sensitivity/specificity of Rv3871, Rv3874, Rv3875, Rv3876, and Rv3879 for PTB detection was 81.21%/74.74%, 63.09%/94.78%, 32.21%/87.37%, 62.42%/85.26%, and 83.56%/83.16%, respectively. Furthermore, the optimal result for PTB diagnosis was achieved by combining antigens Rv3871, Rv3876, and Rv3879. In addition, the IgG levels of Rv3871, Rv3876, and Rv3879 were found to be higher in S-/C+ PTB patients than in other PTB populations. More importantly, combination of the three antigens demonstrated superior diagnostic performance for both S-/C+ and S-/C- PTB. In conclusion, the combination of Rv3871, Rv3876, and Rv3879 induced higher IgG response in sputum S-/C+ PTB patients and represents a promising biomarker combination for diagnosing of PTB. PMID- 26885518 TI - The Causes of HIV-Associated Cardiomyopathy: A Tale of Two Worlds. AB - Antiretroviral therapy (ART) has transformed the clinical profile of human immunodeficiency virus (HIV) from an acute infection with a high mortality into a treatable, chronic disease. As a result, the clinical sequelae of HIV infection are changing as patients live longer. HIV-associated cardiomyopathy (HIVAC) is a stage IV, HIV-defining illness and remains a significant cause of morbidity and mortality among HIV-infected individuals despite ART. Causes and clinical manifestations of HIVAC depend on the degree of host immunosuppression. Myocarditis from direct HIV toxicity, opportunistic infections, and nutritional deficiencies are implicated in causing HIVAC when HIV viral replication is unchecked, whereas cardiac autoimmunity, chronic inflammation, and ART cardiotoxicity contribute to HIVAC in individuals with suppressed viral loads. The initiation of ART has dramatically changed the clinical manifestation of HIVAC in high income countries from one of severe, left ventricular systolic dysfunction to a pattern of subclinical cardiac dysfunction characterized by abnormal diastolic function and strain. In low and middle income countries, however, HIVAC is the most common HIV-associated cardiovascular disease. Clear diagnostic and treatment guidelines for HIVAC are currently lacking but should be prioritized given the global burden of HIVAC. PMID- 26885521 TI - Neurovascular Disorders: Novel Perspectives on Pathogenesis, Diagnosis, and Treatment. PMID- 26885519 TI - Deconstructing Complex Multimorbidity in the Very Old: Findings from the Newcastle 85+ Study. AB - OBJECTIVES: To examine the extent and complexity of the morbidity burden in 85 year-olds; identify patterns within multimorbidity; and explore associations with medication and healthcare use. Participants. 710 men and women; mean (SD) age 85.5 (0.4) years. METHODS: Data on 20 chronic conditions (diseases and geriatric conditions) ascertained from general practice records and participant assessment. Cluster analysis within the multimorbid sample identified subgroups sharing morbidity profiles. Clusters were compared on medication and healthcare use. RESULTS: 92.7% (658/710) of participants had multimorbidity; median number of conditions: 4 (IQR 3-6). Cluster analysis (multimorbid sample) identified five subgroups sharing similar morbidity profiles; 60.0% (395/658) of participants belonged to one of two high morbidity clusters, with only 4.9% (32/658) in the healthiest cluster. Healthcare use was high, with polypharmacy (>=5 medications) in 69.8% (459/658). Between-cluster differences were found in medication count (p = 0.0001); hospital admissions (p = 0.022); and general practitioner (p = 0.034) and practice nurse consultations (p = 0.011). Morbidity load was related to medication burden and use of some, but not all, healthcare services. CONCLUSIONS: The majority of 85-year-olds had extensive and complex morbidity. Elaborating participant clusters sharing similar morbidity profiles will help inform future healthcare provision and the identification of common underlying biological mechanisms. PMID- 26885520 TI - Automatic Classification of Specific Melanocytic Lesions Using Artificial Intelligence. AB - BACKGROUND: Given its propensity to metastasize, and lack of effective therapies for most patients with advanced disease, early detection of melanoma is a clinical imperative. Different computer-aided diagnosis (CAD) systems have been proposed to increase the specificity and sensitivity of melanoma detection. Although such computer programs are developed for different diagnostic algorithms, to the best of our knowledge, a system to classify different melanocytic lesions has not been proposed yet. METHOD: In this research we present a new approach to the classification of melanocytic lesions. This work is focused not only on categorization of skin lesions as benign or malignant but also on specifying the exact type of a skin lesion including melanoma, Clark nevus, Spitz/Reed nevus, and blue nevus. The proposed automatic algorithm contains the following steps: image enhancement, lesion segmentation, feature extraction, and selection as well as classification. RESULTS: The algorithm has been tested on 300 dermoscopic images and achieved accuracy of 92% indicating that the proposed approach classified most of the melanocytic lesions correctly. CONCLUSIONS: A proposed system can not only help to precisely diagnose the type of the skin mole but also decrease the amount of biopsies and reduce the morbidity related to skin lesion excision. PMID- 26885522 TI - Prevalence and Clinical Characteristics of Mycobacterial Diseases in the Barletta Andria-Trani Province, Italy (2005-2013). AB - Tuberculosis remains one of the major worldwide problems regarding public health. This study evaluates the burden of this disease in the BAT Province of the Apulia region (Italy); 12,295 patients were studied, including 310 immigrants. Tubercular disease and mycobacteriosis were found in 129 patients. The number of new TB cases/year ranged from three in 2005 to 12 in 2009. TB was more frequently localized in the lung (70.5%). 14.4% of cases were institutionalized patients for severe neurological and/or psychiatric disease. The database evidenced certain aspects of our study population: the large number of TB patients institutionalized between natives, but no larger presence of TB among HIV positive patients in immigrants compared to Italians. Our findings should help to redefine the alarm regarding the spread of an epidemical form of TB but also to present certain criticisms regarding patient management (especially immigrants) regarding costs, hospitalization, and difficulty of reinstating the patient in the community. Further our data underscore the importance of prevalence of TB in bedridden, institutionalized patients. PMID- 26885523 TI - Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction. AB - This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group), or burn injury combined with seawater immersion (BI group), or only immersion in seawater (I group), or control animals with no injury or immersion (C group). The circulating endothelial cell (CEC) count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P < 0.05). The von Willebrand factor (vWF) activity, plasminogen activator inhibitor (PAI-1), and the ratio of thromboxane B2 (TXB2) to 6-keto-prostaglandin F1alpha (6-K-PGF1alpha ) in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA) in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis. PMID- 26885524 TI - Characterization of Enhancing MS Lesions by Dynamic Texture Parameter Analysis of Dynamic Susceptibility Perfusion Imaging. AB - PURPOSE: The purpose of this study was to investigate statistical differences with MR perfusion imaging features that reflect the dynamics of Gadolinium-uptake in MS lesions using dynamic texture parameter analysis (DTPA). METHODS: We investigated 51 MS lesions (25 enhancing, 26 nonenhancing lesions) of 12 patients. Enhancing lesions (n = 25) were prestratified into enhancing lesions with increased permeability (EL+; n = 11) and enhancing lesions with subtle permeability (EL-; n = 14). Histogram-based feature maps were computed from the raw DSC-image time series and the corresponding texture parameters were analyzed during the inflow, outflow, and reperfusion time intervals. RESULTS: Significant differences (p < 0.05) were found between EL+ and EL- and between EL+ and nonenhancing inactive lesions (NEL). Main effects between EL+ versus EL- and EL+ versus NEL were observed during reperfusion (mainly in mean and standard deviation (SD): EL+ versus EL- and EL+ versus NEL), while EL- and NEL differed only in their SD during outflow. CONCLUSION: DTPA allows grading enhancing MS lesions according to their perfusion characteristics. Texture parameters of EL- were similar to NEL, while EL+ differed significantly from EL- and NEL. Dynamic texture analysis may thus be further investigated as noninvasive endogenous marker of lesion formation and restoration. PMID- 26885525 TI - Biomechanical Comparison of Pedicle Screw Augmented with Different Volumes of Polymethylmethacrylate in Osteoporotic and Severely Osteoporotic Synthetic Bone Blocks in Primary Implantation: An Experimental Study. AB - This study was designed to compare screw stabilities augmented with different volumes of PMMA and analyze relationship between screw stability and volume of PMMA and optimum volume of PMMA in different bone condition. Osteoporotic and severely osteoporotic synthetic bone blocks were divided into groups A0-A5 and B0 B5, respectively. Different volumes of PMMA were injected in groups A0 to A5 and B0 to B5. Axial pullout tests were performed and F max was measured. F max in groups A1-A5 were all significantly higher than group A0. Except between groups A1 and A2, A3 and A4, and A4 and A5, there were significant differences on F max between any other two groups. F max in groups B1-B5 were all significantly higher than group B0. Except between groups B1 and B2, B2 and B3, and B4 and B5, there were significant differences on F max between any other two groups. There was significantly positive correlation between F max and volume of PMMA in osteoporotic and severely osteoporotic blocks. PMMA can significantly enhance pedicle screw stability in osteoporosis and severe osteoporosis. There were positive correlations between screw stability and volume of PMMA. In this study, injection of 3 mL and 4 mL PMMA was preferred in osteoporotic and severely osteoporotic blocks, respectively. PMID- 26885526 TI - High Intensity Resistance Training Methods with and without Protein Supplementation to Fight Cardiometabolic Risk in Middle-Aged Males: A Randomized Controlled Trial. AB - Time-effective protocols may potentially increase people's compliance with exercise. The purpose of this paper was to compare the relative effects of 16 weeks of high intensity (resistance) training (HIT) with and without protein supplementation (HIT&P) and HVHIT (high volume/high intensity training) versus a nontraining control group on cardiometabolic risk factors. One hundred and twenty untrained males 30-50 years old were randomly assigned to 3 subgroups: (a) a HIT group; (b) a HIT&P group, and (c) a waiting-control group (phase I) that crossed over to (d) high volume/high intensity training (HVHIT) during the second study phase. HIT was defined as "single set to failure protocol" while HVHIT consistently applied two sets. Protein supplementation provided an overall intake of 1.5 g/kg/body mass. Primary study endpoint was the metabolic syndrome Z-Score (MetS-Z-Score). MetS-Z-Score significantly improved in all exercise groups (p <= 0.001) with no significant difference between HIT, HIT&P, and HVHIT (p >= 0.829). However, all the exercise groups differed significantly from the CG (p < 0.001) which deteriorated significantly (p = 0.039). In conclusion, all exercise protocols were similarly effective in improving cardiometabolic risk factors. Thus, HIT may be the best choice for people with low time budgets looking to improve their cardiometabolic health. PMID- 26885527 TI - Lifestyle Interventions to Prevent Type 2 Diabetes: A Systematic Review of Economic Evaluation Studies. AB - Objective. To summarize key findings of economic evaluations of lifestyle interventions for the primary prevention of type 2 diabetes (T2D) in high-risk subjects. Methods. We conducted a systematic review of peer-reviewed original studies published since January 2009 in English, French, and Spanish. Eligible studies were identified through relevant databases including PubMed, Medline, National Health Services Economic Evaluation, CINHAL, EconLit, Web of sciences, EMBASE, and the Latin American and Caribbean Health Sciences Literature. Studies targeting obesity were also included. Data were extracted using a standardized method. The BMJ checklist was used to assess study quality. The heterogeneity of lifestyle interventions precluded a meta-analysis. Results. Overall, 20 studies were retained, including six focusing on obesity control. Seven were conducted within trials and 13 using modeling techniques. T2D prevention by physical activity or diet or both proved cost-effective according to accepted thresholds, except for five inconclusive studies, three on diabetes prevention and two on obesity control. Most studies exhibited limitations in reporting results, primarily with regard to generalizability and justification of selected sensitivity parameters. Conclusion. This confirms that lifestyle interventions for the primary prevention of diabetes are cost-effective. Such interventions should be further promoted as sound investment in the fight against diabetes. PMID- 26885528 TI - Clinical Trial Assessing the Efficacy of Gabapentin Plus B Complex (B1/B12) versus Pregabalin for Treating Painful Diabetic Neuropathy. AB - INTRODUCTION: Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN. METHOD: Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment. RESULTS: Both drugs showed reduction of pain intensity, without significant statistical difference (P = 0.900). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P = 0.014. CONCLUSIONS: Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298. PMID- 26885532 TI - New Horizons in Diabetology. PMID- 26885529 TI - Treatment with Tacrolimus and Sirolimus Reveals No Additional Adverse Effects on Human Islets In Vitro Compared to Each Drug Alone but They Are Reduced by Adding Glucocorticoids. AB - Tacrolimus and sirolimus are important immunosuppressive drugs used in human islet transplantation; however, they are linked to detrimental effects on islets and reduction of long-term graft function. Few studies investigate the direct effects of these drugs combined in parallel with single drug exposure. Human islets were treated with or without tacrolimus (30 MUg/L), sirolimus (30 MUg/L), or a combination thereof for 24 hrs. Islet function as well as apoptosis was assessed by glucose-stimulated insulin secretion (GSIS) and Cell Death ELISA. Proinflammatory cytokines were analysed by qRT-PCR and Bio-Plex. Islets exposed to the combination of sirolimus and tacrolimus were treated with or without methylprednisolone (1000 MUg/L) and the expression of the proinflammatory cytokines was investigated. We found the following: (i) No additive reduction in function and viability in islets existed when tacrolimus and sirolimus were combined compared to the single drug. (ii) Increased expression of proinflammatory cytokines mRNA and protein levels in islets took place. (iii) Methylprednisolone significantly decreased the proinflammatory response in islets induced by the drug combination. Although human islets are prone to direct toxic effect of tacrolimus and sirolimus, we found no additive effects of the drug combination. Short-term exposure of glucocorticoids could effectively reduce the proinflammatory response in human islets induced by the combination of tacrolimus and sirolimus. PMID- 26885530 TI - Vitamin D Deficiency Is Not Associated with Diabetic Retinopathy or Maculopathy. AB - BACKGROUND: Experimental and clinical studies suggest a possible association between vitamin D deficiency and both diabetic retinopathy and maculopathy. METHODS: We have performed a cross-sectional study in adults with types 1 and 2 diabetes mellitus. The relationship between the presence and severity of diabetic retinopathy and maculopathy with serum 25-hydroxyvitamin D concentration was evaluated using logistic regression analyses in the presence of demographic and clinical covariates. RESULTS: 657 adults with diabetes were stratified based on retinopathy grading: No Diabetic Retinopathy (39%), Background Diabetic Retinopathy (37%), Preproliferative Diabetic Retinopathy (21%), and Proliferative Diabetic Retinopathy (3%), respectively. There were no differences in serum 25 hydroxyvitamin D concentrations (25(OH)D) between the groups (15.3 +/- 9.0 versus 16.4 +/- 10.5 versus 15.9 +/- 10.4 versus 15.7 +/- 8.5 ng/mL, P = NS). Logistic regression analysis demonstrated no statistically significant relationship between the severity of retinopathy and serum 25(OH)D. Furthermore, there was no difference in serum 25(OH)D between those with (n = 94, 14%) and those without (n = 563, 86%) Diabetic Maculopathy (16.2 +/- 10.0 versus 15.8 +/- 9.8, P = NS) and no relationship was demonstrated by logistic regression analyses between the two variables. CONCLUSIONS: This study has found no association between serum 25(OH)D and the presence and severity of diabetic retinopathy or maculopathy. PMID- 26885531 TI - High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia. AB - Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9-17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. PMID- 26885533 TI - Gq-Coupled Receptors in Autoimmunity. AB - Heterotrimeric G proteins can be divided into Gi, Gs, Gq/11, and G12/13 subfamilies according to their alpha subunits. The main function of G proteins is transducing signals from G protein coupled receptors (GPCRs), a family of seven transmembrane receptors. In recent years, studies have demonstrated that GPCRs interact with Gq, a member of the Gq/11 subfamily of G proteins. This interaction facilitates the vital role of this family of proteins in immune regulation and autoimmunity, particularly for Galphaq, which is considered the functional alpha subunit of Gq protein. Therefore, understanding the mechanisms through which Gq coupled receptors control autoreactive lymphocytes is critical and may provide insights into the treatment of autoimmune disorders. In this review, we summarize recent advances in studies of the role of Gq-coupled receptors in autoimmunity, with a focus on their pathologic role and downstream signaling. PMID- 26885536 TI - Livedoid Dermatitis Treated With Nifedipine. AB - Intravenous injection of buprenorphine as a cause of livedoid dermatitis is a recently described phenomenon. This report reviews the brief literature of this finding, and presents a case of livedoid dermatitis of both heels following injection more than one day prior, and thesuccessful treatment with nifedipine monotherapy. PMID- 26885534 TI - Monocyte Activation in Immunopathology: Cellular Test for Development of Diagnostics and Therapy. AB - Several highly prevalent human diseases are associated with immunopathology. Alterations in the immune system are found in such life-threatening disorders as cancer and atherosclerosis. Monocyte activation followed by macrophage polarization is an important step in normal immune response to pathogens and other relevant stimuli. Depending on the nature of the activation signal, macrophages can acquire pro- or anti-inflammatory phenotypes that are characterized by the expression of distinct patterns of secreted cytokines and surface antigens. This process is disturbed in immunopathologies resulting in abnormal monocyte activation and/or bias of macrophage polarization towards one or the other phenotype. Such alterations could be used as important diagnostic markers and also as possible targets for the development of immunomodulating therapy. Recently developed cellular tests are designed to analyze the phenotype and activity of living cells circulating in patient's bloodstream. Monocyte/macrophage activation test is a successful example of cellular test relevant for atherosclerosis and oncopathology. This test demonstrated changes in macrophage activation in subclinical atherosclerosis and breast cancer and could also be used for screening a panel of natural agents with immunomodulatory activity. Further development of cellular tests will allow broadening the scope of their clinical implication. Such tests may become useful tools for drug research and therapy optimization. PMID- 26885537 TI - Reasons to Investigate the Soluble Receptor for Advanced Glycation End-Product (sRAGE) Pathway in Aortic Disease. AB - Aortic disease has a high rate of morbidity and mortality, and there are no documented screening methods to date. Yet biochemical research does show a significant link between soluble receptor for advanced glycation end-products (sRAGE) protein and cardiovascular disease. Therefore, it can be hypothesized that sRAGE plasma levels may help differentiate patients with aortic disease from the general population, which this paper will review and present. PMID- 26885535 TI - Annexin A1 and the Resolution of Inflammation: Modulation of Neutrophil Recruitment, Apoptosis, and Clearance. AB - Neutrophils (also named polymorphonuclear leukocytes or PMN) are essential components of the immune system, rapidly recruited to sites of inflammation, providing the first line of defense against invading pathogens. Since neutrophils can also cause tissue damage, their fine-tuned regulation at the inflammatory site is required for proper resolution of inflammation. Annexin A1 (AnxA1), also known as lipocortin-1, is an endogenous glucocorticoid-regulated protein, which is able to counterregulate the inflammatory events restoring homeostasis. AnxA1 and its mimetic peptides inhibit neutrophil tissue accumulation by reducing leukocyte infiltration and activating neutrophil apoptosis. AnxA1 also promotes monocyte recruitment and clearance of apoptotic leukocytes by macrophages. More recently, some evidence has suggested the ability of AnxA1 to induce macrophage reprogramming toward a resolving phenotype, resulting in reduced production of proinflammatory cytokines and increased release of immunosuppressive and proresolving molecules. The combination of these mechanisms results in an effective resolution of inflammation, pointing to AnxA1 as a promising tool for the development of new therapeutic strategies to treat inflammatory diseases. PMID- 26885538 TI - Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark: Nationwide Retrospective Cohort Study. AB - Background. Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children with inactivated diphtheria tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods. A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses of DTaP-IPV-Hib, were observed from 24 months (first OPV dose) to 36 months of age. Results. Oral polio vaccine was associated with a lower rate of admissions with any type of non-polio infection compared with DTaP-IPV-Hib as most recent vaccine (adjusted incidence rate ratio [IRR], 0.85; 95% confidence interval [CI], .77-.95). The association was separately significant for admissions with lower respiratory infections (adjusted IRR, 0.73; 95% CI, .61-.87). The admission rates did not differ for OPV versus MMR. Conclusions. Like MMR, OPV was associated with fewer admissions for lower respiratory infections than having DTaP-IPV-Hib as the most recent vaccination. Because OPV is now being phased-out globally, further studies of the potential beneficial nonspecific effects of OPV are warranted. PMID- 26885539 TI - A Cumulative Spore Killing Approach: Synergistic Sporicidal Activity of Dilute Peracetic Acid and Ethanol at Low pH Against Clostridium difficile and Bacillus subtilis Spores. AB - Background. Alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with pH 1.5-2 that were as effective as soap and water washing in reducing levels of C difficile spores on hands. We hypothesized that the addition of dilute peracetic acid (PAA) to acidified ethanol would enhance sporicidal activity while allowing elevation of the pH to a level likely to be well tolerated on skin (ie, >3). Methods. We tested the efficacy of acidified ethanol solutions alone or in combination with PAA against C difficile and Bacillus subtilis spores in vitro and against nontoxigenic C difficile spores on hands of volunteers. Results. Acidification of ethanol induced rapid sporicidal activity against C difficile and to a lesser extent B subtilis. The addition of dilute PAA to acidified ethanol resulted in synergistic enhancement of sporicidal activity in a dose-dependent fashion in vitro. On hands, the addition of 1200-2000 ppm PAA enhanced the effectiveness of acidified ethanol formulations, resulting in formulations with pH >3 that were as effective as soap and water washing. Conclusions. Acidification and the addition of dilute PAA induced rapid sporicidal activity in ethanol. Our findings suggest that it may be feasible to develop effective sporicidal ethanol formulations that are safe and tolerable on skin. PMID- 26885540 TI - Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1. AB - In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms. PMID- 26885541 TI - Management of Multiple Myeloma Complicated by Hepatitis C Virus Reactivation: The Role of New Antiviral Therapy. AB - Reactivation of chronic hepatitis C virus (HCV) infection has been reported in cancer patients receiving chemotherapy. In this study, we report the first case, to our knowledge, of thalidomide-induced acute exacerbation and reactivation of chronic HCV infection complicating management of multiple myeloma. Sofosbuvir based antiviral therapy helped achieve viral clearance and normalization of liver enzymes, thus allowing access to future potentially life-saving chemotherapy agents. PMID- 26885542 TI - Molecular and Culture-Based Bronchoalveolar Lavage Fluid Testing for the Diagnosis of Cytomegalovirus Pneumonitis. AB - Background. Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients, with CMV pneumonitis among the most severe manifestations of infection. Although bronchoalveolar lavage (BAL) samples are frequently tested for CMV, the clinical utility of such testing remains uncertain. Methods. Retrospective analysis of adult patients undergoing BAL testing via CMV polymerase chain reaction (PCR), shell vial culture, and conventional viral culture between August 2008 and May 2011 was performed. Cytomegalovirus diagnostic methods were compared with a comprehensive definition of CMV pneumonitis that takes into account signs and symptoms, underlying host immunodeficiency, radiographic findings, and laboratory results. Results. Seven hundred five patients underwent 1077 bronchoscopy episodes with 1090 BAL specimens sent for CMV testing. Cytomegalovirus-positive patients were more likely to be hematopoietic cell transplant recipients (26% vs 8%, P < .0001) and less likely to have an underlying condition not typically associated with lung disease (3% vs 20%, P < .0001). Histopathology was performed in only 17.3% of CMV positive bronchoscopy episodes. When CMV diagnostic methods were evaluated against the comprehensive definition, the sensitivity and specificity of PCR, shell vial culture, and conventional culture were 91.3% and 94.6%, 54.4% and 97.4%, and 28.3% and 96.5%, respectively. Compared with culture, PCR provided significantly higher sensitivity and negative predictive value (P <= .001), without significantly lower positive predictive value. Cytomegalovirus quantitation did not improve test performance, resulting in a receiver operating characteristic curve with an area under the curve of 0.53. Conclusions. Cytomegalovirus PCR combined with a comprehensive clinical definition provides a pragmatic approach for the diagnosis of CMV pneumonitis. PMID- 26885543 TI - Risk Factors and Outcomes for Carbapenem-Resistant Klebsiella pneumoniae Isolation, Stratified by Its Multilocus Sequence Typing: ST258 Versus Non-ST258. AB - A "high risk" clone of carbapenem-resistant Klebsiella pneumoniae (CRKP) identified by multilocus sequence typing (MLST) as sequence type (ST) 258 has disseminated worldwide. As the molecular epidemiology of the CRE pandemic continues to evolve, the clinical impact of non-ST258 strains is less well defined. We conducted an epidemiological investigation of CRKP based on strains MLST. Among 68 CRKP patients, 61 were ST258 and 7 belonged to non-ST258. Klebsiella pneumoniae ST258 strains were significantly associated with bla KPC production and with resistance to an increased number of antimicrobials. Clinical outcomes were not different. Based on this analysis, one cannot rely solely on the presence of bla KPC in order to diagnose CRKP. PMID- 26885545 TI - Respiratory Viral Testing and Influenza Antiviral Prescriptions During Hospitalization for Acute Respiratory Illnesses. AB - We examined respiratory viral testing and influenza antiviral prescriptions at a US tertiary care hospital. During the 2010-11 to 2012-13 influenza seasons, antiviral prescriptions among acute respiratory illness (ARI) hospitalizations were associated with viral testing (rate ratio = 15.0), and empiric prescriptions were rare (<1% of ARI hospitalizations). PMID- 26885544 TI - Hepatitis C Screening in People With Human Immunodeficiency Virus: Lessons Learned From Syphilis Screening. AB - Background. The incidence of hepatitis C virus (HCV) infection is increasing in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). New guidelines recommend annual screening for HCV, similar to recommendations for syphilis screening with rapid plasma reagin (RPR). Methods. This study compares the frequency of repeat HCV antibody (Ab) testing to repeat RPR testing in a retrospective chart review of 359 HCVAb-negative people living with HIV (PLWH) observed in an Infectious Diseases clinic. Patients were classified into risk groups based on sexual risk factors. Results. Although 85% of PLWH had repeat syphilis screening, less than two thirds had repeat HCVAb screening. The MSM status was associated with increased HCVAb and RPR testing (adjusted odds ratio, 2.6 and 5.9, respectively). Seven persons had incident HCV infection: 3 were MSM, and 4 had symptoms or abnormal laboratory results to prompt testing. Conclusions. Failure to find incident HCV infection in PLWH represents missed opportunities to cure HCV infection and prevent progressive liver disease. Further quality improvement studies are necessary to develop physician-focused interventions to increase HCV screening rates in PLWH. PMID- 26885546 TI - Senior Center-Based Hepatitis C Screening in Baltimore. AB - Despite significant advancements in hepatitis C virus (HCV) treatments, the majority of individuals infected with HCV remain undiagnosed. We report on senior citizen center-based HCV testing in Baltimore, which revealed a 9.4% prevalence of infection. Our data suggest that community-based HCV testing and linkage to care in appropriate settings is feasible and high yield. PMID- 26885547 TI - Completion Rate and Side-Effect Profile of Three-Month Isoniazid and Rifapentine Treatment for Latent Tuberculosis Infection in an Urban County Jail. AB - In an urban jail population, 3 months of isoniazid and rifapentine (3HP) was associated with an 85% latent tuberculosis infection treatment completion rate compared with 18% in a standard 9-month isoniazid treatment group. Among the 91 patients who started 3HP therapy, there were 2 treatment discontinuations from adverse drug reactions. PMID- 26885548 TI - On the Exploration of Adaptive Mechanisms Providing Reliability in Clustered WSNs for Power Plant Monitoring. AB - Wireless Sensor Networks (WSNs) are used in almost every sensing and detection environment instead of wired devices in the current world, all the more in power plant monitoring applications. In such a kind of environment, providing reliability is a challenging task, since WSN makes use of low powered sensors. There are many existing works that provide reliable transmission in WSN (predominantly via multipath routing). However, most of the existing works take additional delay, excessive packet loss, and energy consumption, and hence they provide less packet delivery and throughput. Adaptive Priority Routing (APR) is first proposed during the initial design to provide efficiency in next hop selection. APR computes the priority value for selecting the intermediate nodes during the data transmission in order to improve the packet delivery, throughput, and energy efficiency. In addition to this, APR is developed into QAPR protocol to provide reliability which can operate in two modes, D representing distance mode and Q representing quality of service (QoS) mode. The proposed work is simulated in both flat topology and hierarchical topologies and the simulation analysis shows that the reliability is increased significantly in comparison with existing works. PMID- 26885550 TI - Object lessons: The matula. PMID- 26885551 TI - The art of medicine: Social medicine: lessons from Cuba. PMID- 26885552 TI - Enter Mepolizumab, Better Late Than Never. PMID- 26885553 TI - Minutes count. Designs that improve ED performance. PMID- 26885554 TI - Expressing kindness and compassion. PMID- 26885555 TI - Palliative care--a key objective in health. PMID- 26885556 TI - Caring for drug-affected patients in EDs. PMID- 26885557 TI - Aged care: Equal pay meetings underway. PMID- 26885558 TI - Ultrastrong, Chemically Resistant Reduced Graphene Oxide-based Multilayer Thin Films with Damage Detection Capability. AB - Multilayer thin films of graphene oxide (GO) and poly(vinylamine) (PVAm) were deposited via layer-by-layer assembly. Poly(vinylamine) pH was used to tailor film thickness and GO layer spacing. Graphene oxide concentration in the films was controlled through simple pH adjustment. Thermal reduction of the PVAm/GO multilayer thin films rendered them electrically conductive, which could be further tailored with PVAm pH. These reduced films also exhibited exceptionally high elastic modulus of 30 GPa and hardness of 1.8 GPa, which are among the highest of any graphene-filled polymer composite values ever reported. Cross linking of these films with glutaraldehyde improved their chemical resistance, allowing them to survive strongly acidic or salty solutions. Additionally, scratches in the films can be instantaneously detected by a simple electrical resistance measurement. These films are promising for a variety of packaging and electronic applications. PMID- 26885559 TI - Glabellar dermoid cyst: A case presentation. AB - Dermoid cysts are one of the most common non-inflammatory space-occupying orbital lesions in the pediatric population. They are ectodermal cysts which may contain squamous epithelium with dermal contents such as skin, hair follicles, sebaceous glands, or sweat glands. Dermoid cyts are often innocent, however complications such as inflammation of the fistula or preseptal cellulitis are occasionally seen. We present a case of a 6-year-old girl with a glabellar dermoid cyst and describe the appropriate investigations and definitive treatment. PMID- 26885561 TI - Potential Interference of Protein-Protein Interactions by Graphyne. AB - Graphyne has attracted tremendous attention recently due to its many potentially superior properties relative to those of graphene. Although extensive efforts have been devoted to explore the applicability of graphyne as an alternative nanomaterial for state-of-the-art nanotechnology (including biomedical applications), knowledge regarding its possible adverse effects to biological cells is still lacking. Here, using large-scale all-atom molecular dynamics simulations, we investigate the potential toxicity of graphyne by interfering a protein-protein interaction (ppI). We found that graphyne could indeed disrupt the ppIs by cutting through the protein-protein interface and separating the protein complex into noncontacting ones, due to graphyne's dispersive and hydrophobic interaction with the hydrophobic residues residing at the dimer interface. Our results help to elucidate the mechanism of interaction between graphyne and ppI networks within a biological cell and provide insights for its hazard reduction. PMID- 26885560 TI - Vestibular Dysfunction after Subconcussive Head Impact. AB - Current thinking views mild head impact (i.e., subconcussion) as an underrecognized phenomenon that has the ability to cause significant current and future detrimental neurological effects. Repeated mild impacts to the head, however, often display no observable behavioral deficits based on standard clinical tests, which may lack sensitivity. The current study investigates the effects of subconcussive impacts from soccer heading with innovative measures of vestibular function and walking stability in a pre- 0-2 h, post- 24 h post heading repeated measures design. The heading group (n = 10) executed 10 headers with soccer balls projected at a velocity of 25 mph (11.2 m/sec) over 10 min. Subjects were evaluated 24 h before, immediately after, and 24 h after soccer heading with: the modified Balance Error Scoring System (mBESS); a walking stability task with visual feedback of trunk movement; and galvanic vestibular stimulation (GVS) while standing with eyes closed on foam. A control group (n = 10) followed the same protocol with no heading. The results showed significant decrease in trunk angle, leg angle gain, and center of mass gain relative to GVS for the heading group compared with controls. Medial-lateral trunk orientation displacement and velocity during treadmill walking increased immediately after mild head impact for the heading group compared with controls. Controls showed an improvement in mBESS scores over time, indicating a learning effect, which was not observed with the heading group. These results suggest that mild head impact leads to a transient dysfunction in vestibular processing, which deters walking stability during task performance. PMID- 26885562 TI - Slow-Injection Growth of Seeded CdSe/CdS Nanorods with Unity Fluorescence Quantum Yield and Complete Shell to Core Energy Transfer. AB - A two-step process has been developed for growing the shell of CdSe/CdS core/shell nanorods. The method combines an established fast-injection-based step to create the initial elongated shell with a second slow-injection growth that allows for a systematic variation of the shell thickness while maintaining a high degree of monodispersity at the batch level and enhancing the uniformity at the single-nanorod level. The second growth step resulted in nanorods exhibiting a fluorescence quantum yield up to 100% as well as effectively complete energy transfer from the shell to the core. This improvement suggests that the second step is associated with a strong suppression of the nonradiative channels operating both before and after the thermalization of the exciton. This hypothesis is supported by the suppression of a defect band, ubiquitous to CdSe based nanocrystals after the second growth. PMID- 26885563 TI - Surface-Enhanced Raman Spectroscopy for Identification of Heavy Metal Arsenic(V) Mediated Enhancing Effect on Antibiotic Resistance. AB - Bacterial antibiotic resistance poses a threat to global public health. Restricted usage of antibiotics does not necessarily prevent its continued emergence. Rapid and sensitive screening of triggers, in addition to antibiotic, and exploring the underlying mechanism are still major challenges. Herein, by developing a homogeneous vacuum filtration-based bacterial sample fabrication enabling high surface-enhanced Raman scattering (SERS) reproducibility across multiple bacterial samples and negating interfering spectral variations from inhomogeneous sample geometry and SERS enhancement, SERS was employed to study heavy metal arsenic [As(V)]-mediated antibiotic resistance in a robust, sensitive, and rapid fashion. Independent and robust spectral changes representing phenotypic bacterial responses, combined with multivariate analysis, clearly identified that As(V) enhanced antibiotic resistance to tetracycline (Tet). Similar spectral alteration profile to As(V) and Tet indicated that cross resistance, whereby As(V)-induced bacterial resistance simultaneously blocked Tet action, could account for the enhanced resistance. The sensitive, robust, and rich phenotypic profile provided by SERS, combined with additional advantages in imposing no need to cultivate bacteria and single-cell sensitivity, can be further exploited to evaluate resistance-intervening factors in real microbiota. PMID- 26885564 TI - Butyrate production from high-fiber diet protects against lymphoma tumor. AB - Gut microbiota and dietary fiber are critical for protecting body from obesity, diabetes and cancer. Butyrate, produced in the gut by bacterial fermentation of dietary fibers, is demonstrated to be protective against the development of colorectal cancer as a histone deacetylase (HDAC) inhibitor. We report that high fiber diet and butyrate significantly inhibited the growth lymphoma tumors. Butyrate induced apoptosis of lymphoma tumor cells and significantly up-regulated histone 3 acetylation (H3ac) level and target genes such as Fas, P21, P27. Our results unravel an instrumental role of fiber diet and their metabolites on lymphoma tumor and demonstrate an intervention potential on the prevention and therapy of lymphoma. PMID- 26885565 TI - Resistance of Strains Producing Extended-Spectrum beta-Lactamases Among Salmonella from Duck Carcasses at Slaughterhouses in Three Major Provinces of South Korea. AB - The current study was carried out to estimate Salmonella spp. contamination of duck carcasses and to determine the antibiotic susceptibility profiles and serotype distribution of the isolates. Salmonella spp. was detected in 21.7% (26/120) of fresh raw duck carcasses sampled at different slaughterhouses in South Korea. Eight Salmonella serovars were identified; the most prevalent serovar was S. Typhimurium (34.6%), followed by S. Virchow (30.8%). All isolates were resistant to at least one antibiotic, and five remarkable isolates were resistant to more than 10 antibiotics, including third- and fourth-generation cephalosporins. Additional phenotypic and genetic characterization demonstrated that these isolates harbored resistance genes to broad-spectrum beta-lactams, blaCTX-M-15 and blaCMY-2 genes, among the most prevalent beta-lactamase enzymes worldwide. Based on molecular subtyping performed using the DiversiLabTM automated repetitive-sequence-based PCR system, isolates were classified into cluster A and cluster B. Among beta-lactamase-producing Salmonellas, the isolate showing >98% similarity in their repetitive-sequence-based PCR banding pattern seemed to have acquired the resistance gene (blaCMY-2) and thus a distinct multiresistance profile. Given that antibiotic-resistant genes might be transferred by plasmid-mediated conjugation, periodic microbiological assessment within slaughterhouses is recommended for pathogens not to be transmitted through cross-contamination during slaughtering and dressing. PMID- 26885566 TI - Estimating Broad Sense Heritability and Investigating the Mechanism of Genetic Transmission of Cold Tolerance Using Mannitol as a Measure of Post-freeze Juice Degradation in Sugarcane and Energycane (Saccharum spp.). AB - In approximately 25% of the sugarcane-producing countries worldwide, conventional sugarcane (Saccharum spp. hybrids) is exposed to damaging freezes. A study was conducted during the 2009 and 2010 harvest seasons to compare late-season freeze tolerance among three groups: commercial Louisiana sugarcane genotypes, early generation genotypes selected for cold tolerance in the U.S. Department of Agriculture sugarcane breeding programs at Houma, LA, and Canal Point, FL, and potential energycane genotypes selected for high total biomass per acre. Mannitol concentrations in cane juice following freezing temperatures were determined to evaluate levels of cold tolerance. Genotypes selected for cold tolerance in Houma, LA, had significantly more late-season freeze tolerance than commercial sugarcane genotypes and genotypes selected in Canal Point, FL. Genotypes showing the most cold tolerance were Ho02-146 and Ho02-152, and those that were most highly susceptible were US87-1006 and US87-1003 (early-generation breeding genotypes) and L99-233 (commercial genotype). Broad-sense heritability for late season cold tolerance in the two-year study was estimated at g(2) = 0.78. The enzymatic mannitol analysis successfully differentiated high-fiber energycane genotypes from those from other sources. PMID- 26885567 TI - Identification and Structure-Activity Relationships of Diarylhydrazides as Novel Potent and Selective Human Enterovirus Inhibitors. AB - Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 MUM against EV71. It is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including EV71 and Coxsackieviruses B1 (CVB1), CVB2, CVB3, CVB4, CVB5, and CVB6 (EC50 as low as 0.5 nM). Compared with the reference antienterovirus drug 1 (enviroxime) and known inhibitor 5 (WIN 51711), the four highly selective compounds 15, 27, 41 and 47 inhibited EV71 replication with EC50 values of 0.17-0.02 MUM and SI values in a range of 978.4-12338. A preliminary mechanistic study indicated that VP1 might be the target site for this type of compound. PMID- 26885568 TI - Reconstruction of Ancestral Genomes in Presence of Gene Gain and Loss. AB - Since most dramatic genomic changes are caused by genome rearrangements as well as gene duplications and gain/loss events, it becomes crucial to understand their mechanisms and reconstruct ancestral genomes of the given genomes. This problem was shown to be NP-complete even in the "simplest" case of three genomes, thus calling for heuristic rather than exact algorithmic solutions. At the same time, a larger number of input genomes may actually simplify the problem in practice as it was earlier illustrated with MGRA, a state-of-the-art software tool for reconstruction of ancestral genomes of multiple genomes. One of the key obstacles for MGRA and other similar tools is presence of breakpoint reuses when the same breakpoint region is broken by several different genome rearrangements in the course of evolution. Furthermore, such tools are often limited to genomes composed of the same genes with each gene present in a single copy in every genome. This limitation makes these tools inapplicable for many biological datasets and degrades the resolution of ancestral reconstructions in diverse datasets. We address these deficiencies by extending the MGRA algorithm to genomes with unequal gene contents. The developed next-generation tool MGRA2 can handle gene gain/loss events and shares the ability of MGRA to reconstruct ancestral genomes uniquely in the case of limited breakpoint reuse. Furthermore, MGRA2 employs a number of novel heuristics to cope with higher breakpoint reuse and process datasets inaccessible for MGRA. In practical experiments, MGRA2 shows superior performance for simulated and real genomes as compared to other ancestral genome reconstruction tools. PMID- 26885569 TI - The evolution of prostacyclins in pulmonary arterial hypertension: from classical treatment to modern management. AB - Prostacyclins for the treatment of pulmonary arterial hypertension (PAH) have historically been covered under the insurance medical benefit because they require durable medical equipment and are administered by an intravenous, subcutaneous, or inhalation route. However, more treatment options that target the prostacyclin pathway have become available. As the number and type of options expand, an improved understanding of these drugs will aid managed care decision makers in evaluating new treatment options and making clinically sound and cost effective treatment decisions. PAH is a progressive disease of pulmonary vascular remodeling that increases pulmonary vascular resistance and often results in right-side heart failure and death if left untreated. Adverse event profiles, the complexity of administration modalities, and potential complications must be considered when administering prostacyclin therapy. Traditional modes of administration, with their potential challenges and complications, may have contributed to the unmet need for an oral agent. Another consideration for managed care decision makers is that oral agents are generally covered under the insurance pharmacy benefit. Access to oral medications with long-term outcomes data, as well as the improved convenience of oral therapy, may help patients with PAH maximize function by maintaining a more convenient and consistent therapeutic regimen. PMID- 26885570 TI - Effect of a High Density of Stacking Faults on the Young's Modulus of GaAs Nanowires. AB - Stacking faults (SFs) are commonly observed crystalline defects in III-V semiconductor nanowires (NWs) that affect a variety of physical properties. Understanding the effect of SFs on NW mechanical properties is critical to NW applications in nanodevices. In this study, the Young's moduli of GaAs NWs with two distinct structures, defect-free single crystalline wurtzite (WZ) and highly defective wurtzite containing a high density of SFs (WZ-SF), are investigated using combined in situ compression transmission electron microscopy and finite element analysis. The Young's moduli of both WZ and WZ-SF GaAs NWs were found to increase with decreasing diameter due to the increasing volume fraction of the native oxide shell. The presence of a high density of SFs was further found to increase the Young's modulus by 13%. This stiffening effect of SFs is attributed to the change in the interatomic bonding configuration at the SFs. PMID- 26885571 TI - Am I Drinking Enough? Yes, No, and Maybe. AB - Adequate fluid intake can be dually defined as a volume of fluid (from water, beverages, and food) sufficient to replace water losses and provide for solute excretion. A wide range of fluid intakes are compatible with euhydration, whereby total body water varies narrowly from day to day by 600 to 900 mL (<1% body mass). One measure of fluid intake adequacy involves enough fluid to prevent meaningful body water deficits outside this euhydration range (i.e., dehydration). Another measure of fluid intake adequacy involves enough fluid to balance the renal solute load, which can vary widely inside the euhydration range. The subtle but important distinction between the 2 types of adequacy may explain some of the ambiguity surrounding the efficacy of hydration status markers. Both perspectives of fluid intake adequacy are discussed in detail and a simple tool is reviewed that may help healthy, active, low-risk populations answer the question, "Am I drinking enough?" Key Teaching Points * Adequate fluid intake can be dually defined as a volume of fluid (from water, beverages, and food) sufficient to replace water losses and provide for solute excretion. * Fluid needs can differ greatly among individuals due to variation in the factors that influence both water loss and solute balance; thus, adequacy is consistent with a wide range of fluid intakes and is better gauged using hydration assessment methods. * Adequacy of fluid intake for replacing meaningful water losses (dehydration) can be assessed simply, inexpensively, and with reasonable fidelity among healthy, active, low-risk individuals. * Adequacy of fluid intake for solute excretion per se can also be assessed among individuals but is more difficult to define and less practical to measure. PMID- 26885572 TI - Antimicrobial Bowel Preparation for Elective Colon Surgery. AB - BACKGROUND: Mechanical bowel preparation continues to be a controversial subject for the pre-operative management of patients undergoing elective colon resection. METHODS: The English literature on bowel preparation was searched to identify pertinent publications. RESULTS: The published literature over the past 80 y confirms that mechanical bowel preparation alone does not reduce surgical site infections. However, the use of appropriate oral antibiotics following mechanical bowel preparation with pre-operative systemic antibiotics reduces rates of surgical site infections and anastomotic leaks when compared with systemic antibiotics alone. CONCLUSIONS: Mechanical bowel preparation with pre-operative oral antibiotics and pre-operative systemic antibiotics are the standard of care for elective colon surgery. Refinement in methods of bowel preparation needs additional clinical investigations to further enhance outcomes. PMID- 26885573 TI - PM2.5 Population Exposure in New Delhi Using a Probabilistic Simulation Framework. AB - This paper presents a Geographical Information System (GIS) based probabilistic simulation framework to estimate PM2.5 population exposure in New Delhi, India. The framework integrates PM2.5 output from spatiotemporal LUR models and trip distribution data using a Gravity model based on zonal data for population, employment and enrollment in educational institutions. Time-activity patterns were derived from a survey of randomly sampled individuals (n = 1012) and in vehicle exposure was estimated using microenvironmental monitoring data based on field measurements. We simulated population exposure for three different scenarios to capture stay-at-home populations (Scenario 1), working population exposed to near-road concentrations during commutes (Scenario 2), and the working population exposed to on-road concentrations during commutes (Scenario 3). Simulated annual average levels of PM2.5 exposure across the entire city were very high, and particularly severe in the winter months: ~200 MUg m(-3) in November, roughly four times higher compared to the lower levels in the monsoon season. Mean annual exposures ranged from 109 MUg m(-3) (IQR: 97-120 MUg m(-3)) for Scenario 1, to 121 MUg m(-3) (IQR: 110-131 MUg m(-3)), and 125 MUg m(-3) (IQR: 114-136 MU gm(-3)) for Scenarios 2 and 3 respectively. Ignoring the effects of mobility causes the average annual PM2.5 population exposure to be underestimated by only 11%. PMID- 26885574 TI - Risk of the Metabolic Syndrome in Sexual Minority Women: Results from the ESTHER Study. AB - OBJECTIVE: Compared to heterosexuals, sexual minority women (SMW) have higher rates of the metabolic syndrome risk factors (e.g., obesity, smoking, heavy drinking, and depression). Yet, no published research has examined whether SMW have higher rates of the metabolic syndrome. The aim of this study is to describe the prevalence of the metabolic syndrome and its individual factors in a sample of heterosexuals and SMW, and identify whether SMW are at greater risk of having the metabolic syndrome. MATERIALS AND METHODS: Data are from the Epidemiologic STudy of HEalth Risk in Women (ESTHER), a cross-sectional convenience sample of 479 SMW and 400 heterosexual women from Pittsburgh, Pennsylvania. Participants provided self-report questionnaire data, clinical data, and blood work. RESULTS: Compared to heterosexuals, SMW had higher mean waist circumference, fasting glucose, and systolic and diastolic blood pressure. Nearly one-quarter (24.3%) of SMW had the metabolic syndrome compared to 15.6% of heterosexual women (p = 0.002). After controlling for demographic and risk factors, SMW had a 44% higher risk of having the metabolic syndrome than heterosexuals (p = 0.031). CONCLUSIONS: To our knowledge, this is the first study to identify this health disparity in SMW. Future studies should explore differential risk of mortality and metabolic health between SMW and heterosexuals. PMID- 26885575 TI - Intravitreal Filariasis: The Accidental Traveler. PMID- 26885576 TI - Intern Boot Camp: Feasibility and impact of a 1-hour session to ensure graduating medical student competency in falls risk assessment. AB - The authors evaluated the feasibility of a 1-hour session to ensure competency in gait and falls risk assessment for medical students at their institution. The session included a history and exam with faculty and staff as standardized patients, gait recognition videos, and case evaluation for falls risk assessment and prevention. Student perceptions were evaluated using a retrospective pre-post survey, scored on a 5-point Likert-type scale. Wilcoxon signed-rank tests were used to assess change and Kruskal-Wallis tests were used to analyze differences by residency choice. A range of five to 11 faculty and staff certified 238 medical students during eight 1-hour sessions. Overall self-perception of competence in falls risk assessment and prevention improved (p <= .001), and did not differ by residency choice, both before and after the training program (p = .73 and p = .25). Feedback was positive. This session is a feasible way to teach and assess the competency for falls risk assessment with modest time commitment. PMID- 26885577 TI - Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients. AB - OBJECTIVE: To report clinical and dosimetric outcomes of a consecutive series of patients with anal cancer treated with volumetric-modulated arc therapy (VMAT) concomitant to chemotherapy (CT). METHODS: A cohort of 39 patients underwent VMAT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumour volume (GTV) and 42 Gy/28 fractions to the elective nodal volumes for patients with cT2N0 disease. Patients with cT3-T4/N0-N3 tumours were prescribed 54 Gy/30 fractions to the GTV and 50.4 Gy/30 fractions to the gross nodal volumes if sized <=3 cm or 54 Gy/30 fractions if > 3 cm. Elective nodal regions were given 45 Gy/30 fractions. CT was administered concurrently following Nigro's regimen. The primary end point was acute toxicity. Secondary end points were colostomy-free survival (CFS), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Dosimetric data are also provided. RESULTS: Median follow up was 21 months. Maximum acute toxicities were: dermatologic-G3: 18%; gastrointestinal-G3: 5%; genitourinary-G3: 2%; anaemia-G2: 7%; leukopenia-G3: 28%; G4: 8%; neutropenia-G3: 13%; G4: 18%; thrombocytopenia-G3: 11%; and G4: 2%. The actuarial 2-year CFS was 77.9% [95% confidence interval (CI): 54-90.4%]. Actuarial 2-year OS and CSS were 85.2% (95% CI: 60.1-95.1%), while DFS was 75.1% (95% CI: 52.4.7-88.1%). CONCLUSION: Our clinical results support the use of VMAT as a safe and effective intensity-modulated radiotherapy (IMRT) option in the combined modality treatment of anal cancer, with consistent dosimetry, mild toxicity and promising sphincter preservation and survival rates. Advances in knowledge: IMRT is a standard of care for patients with anal cancer, and VMAT is a robust technical solution in this setting. PMID- 26885578 TI - Structure and Noncanonical Activities of Coat Proteins of Helical Plant Viruses. AB - The main function of virus coat protein is formation of the capsid that protects the virus genome against degradation. However, besides the structural function, coat proteins have many additional important activities in the infection cycle of the virus and in the defense response of host plants to viral infection. This review focuses on noncanonical functions of coat proteins of helical RNA containing plant viruses with positive genome polarity. Analysis of data on the structural organization of coat proteins of helical viruses has demonstrated that the presence of intrinsically disordered regions within the protein structure plays an important role in implementation of nonstructural functions and largely determines the multifunctionality of coat proteins. PMID- 26885579 TI - Role of Protein L25 and Its Contact with Protein L16 in Maintaining the Active State of Escherichia coli Ribosomes in vivo. AB - A ribosomal protein of the L25 family specifically binding to 5S rRNA is an evolutionary feature of bacteria. Structural studies showed that within the ribosome this protein contacts not only 5S rRNA, but also the C-terminal region of protein L16. Earlier we demonstrated that ribosomes from the DeltaL25 strain of Escherichia coli have reduced functional activity. In the present work, it is established that the reason for this is a fraction of functionally inactive 50S ribosomal subunits. These subunits have a deficit of protein L16 and associate very weakly with 30S subunits. To study the role of the contact of these two proteins in the formation of the active ribosome, we created a number of E. coli strains containing protein L16 with changes in its C-terminal region. We found that some mutations (K133L or K127L/K133L) in this protein lead to a noticeable slowing of cell growth and decrease in the activity of their translational apparatus. As in the case of the ribosomes from the DeltaL25 strain, the fraction of 50S subunits, which are deficient in protein L16, is present in the ribosomes of the mutant strains. All these data indicate that the contact with protein L25 is important for the retention of protein L16 within the E. coli ribosome in vivo. In the light of these findings, the role of the protein of the L25 family in maintaining the active state of the bacterial ribosome is discussed. PMID- 26885580 TI - Calponin-Like Protein from Mussel Smooth Muscle Is a Competitive Inhibitor of Actomyosin ATPase. AB - The goal of this work was to elucidate the mechanism of inhibition of the actin activated ATPase of myosin subfragment-1 (S1) by the calponin-like protein from mussel bivalve muscle. The calponin-like protein (Cap) is a 40-kDa actin-binding protein from the bivalve muscle of the mussel Crenomytilus grayanus. Kinetic parameters Vmax and KATPase of actomyosin ATPase in the absence and the presence of Cap were determined to investigate the mechanism of inhibition. It was found that Cap mainly causes increase in KATPase value and to a lesser extent the decrease in Vmax, which indicates that it is most likely a competitive inhibitor of actomyosin ATPase. Analysis of Vmax and KATPase parameters in the presence of tropomyosin revealed that the latter is a noncompetitive inhibitor of the actomyosin ATPase. PMID- 26885581 TI - Proteomic Analysis of Escherichia coli Protein Fractions Resistant to Solubilization by Ionic Detergents. AB - Amyloids are protein fibrils adopting structure of cross-beta spine exhibiting either pathogenic or functionally significant properties. In prokaryotes, there are several groups of functional amyloids; however, all of them were identified by specialized approaches that do not reveal all cellular amyloids. Here, using our previously developed PSIA (Proteomic Screening and Identification of Amyloids) approach, we have conducted a proteomic screening for candidates for novel amyloid-forming proteins in Escherichia coli as one of the most important model organisms and biotechnological objects. As a result, we identified 61 proteins in fractions resistant to treatment with ionic detergents. We found that a fraction of proteins bearing potentially amyloidogenic regions predicted by bioinformatics algorithms was 3-5-fold more abundant among the identified proteins compared to those observed in the entire E. coli proteome. Almost all identified proteins contained potentially amyloidogenic regions, and four of them (BcsC, MukB, YfbK, and YghJ) have asparagine- and glutamine-rich regions underlying a crucial feature of many known amyloids. In this study, we demonstrate for the first time that at the proteome level there is a correlation between experimentally demonstrated detergent-resistance of proteins and potentially amyloidogenic regions predicted by bioinformatics approaches. The data obtained enable further comprehensive characterization of entirety of amyloids (or amyloidome) in bacterial cells. PMID- 26885582 TI - Recombinant Phospholipase A1 of the Outer Membrane of Psychrotrophic Yersinia pseudotuberculosis: Expression, Purification, and Characterization. AB - The pldA gene encoding membrane-bound phospholipase A1 of Yersinia pseudotuberculosis was cloned and expressed in Escherichia coli cells. Recombinant phospholipase A1 (rPldA) was isolated from inclusion bodies dissolved in 8 M urea by two-stage chromatography (ion-exchange and gel-filtration chromatography) as an inactive monomer. The molecular mass of the rPldA determined by MALDI-TOF MS was 31.7 +/- 0.4 kDa. The highly purified rPldA was refolded by 10-fold dilution with buffer containing 10 mM Triton X-100 and subsequent incubation at room temperature for 16 h. The refolded rPldA hydrolyzed 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine in the presence of calcium ions. The enzyme exhibited maximal activity at 37 degrees C and nearly 40% of maximal activity at 15 degrees C. The phospholipase A1 was active over a wide range of pH from 4 to 11, exhibiting maximal activity at pH 10. Spatial structure models of the monomer and the dimer of Y. pseudotuberculosis phospholipase A1 were constructed, and functionally important amino acid residues of the enzyme were determined. Structural differences between phospholipases A1 from Y. pseudotuberculosis and E. coli, which can affect the functional activity of the enzyme, were revealed. PMID- 26885583 TI - Investigation of Stability of Photosynthetic Reaction Center and Quantum Dot Hybrid Films. AB - The efficiency of interaction (efficiency of energy transfer) between various quantum dots (QDs) and photosynthetic reaction centers (RCs) from the purple bacterium Rhodobacter sphaeroides and conditions of long-term stability of functioning of such hybrid complexes in film preparations were investigated. It was found that dry films containing RCs and QDs and maintained at atmospheric humidity are capable to keep their functional activity for at least some months as judging by results of measurement of their spectral characteristics, efficiency of energy transfer from QDs to RCs, and RC electron-transport activity. Addition of trehalose to the films giving them still greater stability is especially expressed for films maintained at low humidity. These stable hybrid film structures are promising for further biotechnological studies for developing new phototransformation devices. PMID- 26885584 TI - Reoperation for Margins After Breast Conservation Surgery: What's Old Is New Again. PMID- 26885586 TI - Taking action to solve the wellness issue. PMID- 26885588 TI - A call for data on gorillas. PMID- 26885589 TI - What Is Your Diagnosis?: Mediastinal shift. PMID- 26885590 TI - What Is Your Diagnosis?: Primary pulmonary neoplasia. PMID- 26885591 TI - ECG of the Month. PMID- 26885592 TI - Pathology in Practice. PMID- 26885594 TI - Outcomes of ureteral surgery and ureteral stenting in cats: 117 cases (2006 2014). AB - OBJECTIVE: To evaluate and compare outcomes in cats following ureteral surgery or ureteral stent placement. DESIGN: Retrospective case series. ANIMALS: 117 cats. PROCEDURES: Data regarding signalment, history, concurrent disease, clinical signs, clinicopathologic tests, surgical procedures, and perioperative complications (including death) were recorded. Follow-up data, including presence of signs of chronic lower urinary tract disease, chronic urinary tract infection, reobstruction, and death, if applicable, were obtained by records review or telephone contact with owners. Variables of interest were compared statistically between cats treated with and without stent placement. Kaplan-Meier analysis and Cox regression were performed to assess differences in survival time between cats with and without ureteral stents. RESULTS: Perioperative complications referable to the urinary tract were identified in 6 of 43 (14%) cats that had >= 1 ureteral stent placed and 2 of 74 (3%) cats that underwent ureteral surgery without stenting. Perioperative mortality rates were similar between cats with (4/43 [9%]) and without (6/74 [8%]) stents. After surgery, signs of chronic lower urinary tract disease and chronic urinary tract infection were significantly more common among cats with than cats without stents. Nineteen of 87 (22%) cats with follow-up information available had recurrent obstruction; incidence of reobstruction did not differ between cats with and without stents. Median survival time did not differ between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: The potential for signs of chronic lower urinary tract disease and chronic infection, particularly among cats that receive ureteral stents, warrants appropriate client counseling. Judicious long-term follow-up for detection of reobstruction is recommended. PMID- 26885593 TI - Compendium of Animal Rabies Prevention and Control, 2016. PMID- 26885595 TI - Use of endoscopic-assisted argon plasma coagulation for the treatment of colonic vascular ectasia (angiodysplasia) in an adult dog. AB - CASE DESCRIPTION: A 10-year-old neutered male mixed-breed dog was evaluated for a 5-year history of intermittent hematochezia and chronic anemia that were unresponsive to medical treatment. CLINICAL FINDINGS: Colonoscopy revealed multifocal areas of coalescing tortuous mucosal blood vessels throughout the colon and rectum. Colonic vascular ectasia (angiodysplasia) was diagnosed on the basis of the endoscopic appearance of the lesions. TREATMENT AND OUTCOME: The dog failed to respond to traditional medical treatments for colonic vascular ectasia and required multiple plasma and blood transfusions. The dog received 4 endoscopic-assisted argon plasma coagulation treatments, which resulted in long term resolution of gastrointestinal hemorrhage. Colonic perforation occurred during the third argon plasma coagulation treatment. The perforation was surgically repaired. The dog remained free from clinical signs of colonic vascular ectasia for > 1 year after the third argon plasma coagulation treatment and was euthanized because of clinical deterioration associated with progressive heart disease. CLINICAL RELEVANCE: Endoscopic-assisted argon plasma coagulation treatment is a novel treatment for dogs with colonic vascular ectasia and provided long-term resolution of clinical signs for the dog of this report. In human patients, complications associated with endoscopic-assisted argon plasma coagulation treatment include colonic perforation, which also occurred in the dog of this report. PMID- 26885596 TI - Use of botulinum toxin type A for the treatment of radiation therapy-induced myokymia and neuromyotonia in a dog. AB - CASE DESCRIPTION A 5-year-old castrated male Maltese was evaluated for intermittent clinical signs of muscle cramping and abnormal movements of the skin of the right pelvic limb at the site where an infiltrative lipoma had twice been resected. After the second surgery, the surgical field was treated with radiation therapy (RT). The clinical signs developed approximately 14 months after completion of RT. CLINICAL FINDINGS When clinical signs were present, the right biceps femoris and semitendinosus muscles in the area that received RT were firm and had frequently visible contractions, and the skin overlying those muscles had episodic vermiform movements. Electromyography of those muscles revealed abnormal spontaneous activity with characteristics consistent with myokymic discharges and neuromyotonia. Magnetic resonance imaging of the affected leg revealed no evidence of tumor regrowth. The myokymia and neuromyotonia were considered secondary to RT. TREATMENT AND OUTCOME 4 U of Clostridium botulinum toxin type A (BoNT-A) neurotoxin complex was injected into the affected muscles at each of 6 sites twice during a 24-hour period (ie, 48 U of BoNT-A were administered). The clinical signs were completely resolved 10 days after BoNT-A treatment and were controlled by repeated BoNT-A treatment every 3 to 4 months for > 1 year. CLINICAL RELEVANCE To our knowledge, this is the first report of myokymia and neuromyotonia secondary to RT in a dog. For the dog of this report, injection of BoNT-A into the affected muscles was safe, effective, and easy to perform. PMID- 26885597 TI - Urinary bladder retroversion and neourethrocystostomy for treatment of inadvertent prostatectomy and urethrectomy in a dog. AB - CASE DESCRIPTION A 15-month-old male Newfoundland was examined because of an inability to urinate, lethargy, inappetence, and intermittent vomiting that first became evident after bilateral cryptorchidectomy 2 days previously. The patient was referred for further evaluation and treatment. CLINICAL FINDINGS Results of physical examination, serum biochemical analysis, and abdominocentesis led to a diagnosis of uroperitoneum. Retrograde cystography indicated urinary tract obstruction. In view of the history of recent elective cryptorchidectomy, a diagnosis of uroperitoneum with urethral obstruction secondary to iatrogenic prostatectomy and urethrectomy was made. TREATMENT AND OUTCOME During a ventral midline celiotomy, the inadvertent prostatectomy and urethrectomy were found to have resulted in insufficient urethral length for primary repair. Surgical repair of the urethral defect was achieved by means of a novel technique of bladder retroversion and neourethrocystostomy at the apex of the bladder. A urethral stricture evident 1.5 months after surgery was initially treated with balloon dilatation, followed by temporary and then permanent placement of a self expanding metallic stent. At the last follow-up 6.6 years after stent placement, the dog remained continent while receiving phenylpropanolamine and the owner was highly satisfied with the outcome. CLINICAL RELEVANCE Caudal intraabdominal bladder retroversion with apex neourethrocystostomy may be a viable alternative to more complex urethral lengthening procedures in dogs and can potentially preserve lower urinary tract function. This treatment might be considered for patients with urethral trauma or malignant neoplasia necessitating extensive urethral resection. Urethral strictures may be effectively managed with stenting. PMID- 26885598 TI - Use of a percutaneously controlled hydraulic occluder for treatment of refractory urinary incontinence in three female cats. AB - CASE DESCRIPTION 3 cats were referred for evaluation of chronic urinary incontinence. CLINICAL FINDINGS A presumptive diagnosis of urethral sphincter mechanism incompetence (USMI) was made in all 3 cats. Preoperatively, incontinence was mild in 1 cat (incontinence during sleep) and moderate to severe (incontinence while awake and at rest) in 2. Structural abnormalities noted during cystoscopy included urethrovestibular junction stenosis (n = 1), vaginal stenosis (1), short urethra (1), and intrapelvic bladder (1). TREATMENT AND OUTCOME All 3 cats were treated by means of implantation of an inflatable silicone hydraulic occluder (HO) via a ventral midline celiotomy. Immediately prior to HO implantation, patients underwent cystoscopy to detect any anatomic abnormalities and confirm the absence of ureteral ectopia. Following surgery, all 3 patients attained complete continence, needing 0 or 1 inflation of the device. Complications included cystoscopy-associated urethral tear (n = 1), constipation (1), stranguria (1), hematuria (2), and urinary tract infection (2). Device explantation was performed 14 weeks after surgery in 1 cat because of postoperative constipation. Constipation persisted and urinary incontinence recurred but was markedly improved following device removal in this cat (leakage of urine only when sleeping at follow-up 29 months after surgery [26 months after device explantation]). At the time of last follow-up, 2 of the 3 cats remained fully continent approximately 3 and 6 years after device implantation. CLINICAL RELEVANCE Findings suggested that implantation of an HO may be a safe and effective long-term treatment for some cats with USMI. Further studies are necessary to evaluate the potential for treatment-related complications and the long-term outcome. PMID- 26885599 TI - Hydrops associated with chondrodysplasia of the fetus in a miniature Scottish Highland cow. AB - CASE DESCRIPTION A 2-year-old primiparous miniature Scottish Highland cow with an unknown breeding date was evaluated for suspected hydrops. CLINICAL FINDINGS Transabdominal and transrectal ultrasonographic examination identified a large amount of hypoechoic fluid within an enlarged uterus; the fetus could not be identified. Presence of a severely distended uterus and concerns regarding associated health risks to the cow led to the decision to induce labor. Although fluids were expelled, parturition did not progress further over the following 48 hours. Vaginal examination revealed a partially dilated cervix and an abnormally shaped fetus that was too large to pass vaginally. TREATMENT AND OUTCOME Supportive care was provided to the cow, and a stillborn bull calf was delivered by cesarean section. Grossly evident chondrodystrophic dwarfism with hydrocephalus, compatible with so-called bulldog calf malformations, was confirmed by diagnostic imaging and histopathologic evaluation. The cow recovered from surgery uneventfully and was discharged from the hospital the following day. Genetic analysis of DNA from hair roots collected from the sire and dam confirmed both were carriers of an aggrecan-1 gene mutation (bulldog dwarfism1) previously associated with dwarfism and bulldog calf malformations in Dexter cattle. CLINICAL RELEVANCE To our knowledge, this is the first reported case of bulldog calf malformations associated with an aggrecan-1 gene mutation in miniature Scottish Highland cattle, confirming that at least 1 genetic mutation associated with this condition is found in cattle breeds other than Dexter. The findings highlighted the clinical importance of testing for known genetic diseases in breeding cattle, particularly among miniature breeds. PMID- 26885601 TI - Erythematous Plaque in the Cheek of an HIV Patient. PMID- 26885600 TI - Changes in anti-cyclic citrullinated peptide antibodies and rheumatoid factor isotypes serum levels in patients with rheumatoid arthritis following treatment with different biological drugs. AB - OBJECTIVES: Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a serological marker of rheumatoid arthritis (RA), and also have a prognostic value for more aggressive disease. Whether anti-CCP levels may change during treatment according to clinical response is matter of debate. Likewise, it is unknown whether different biological drugs have peculiar effects on anti-CCP levels. This study aimed to investigate changes in anti-CCP serum levels in RA patients on biological drugs with different mechanism of action. METHODS: We studied 71 patients with active RA tested positive for anti-CCP who started a first biological drug (54 anti-TNF-alpha drug, 9 rituximab, 8 tocilizumab). In 14 patients stopping anti-TNF-alpha treatment for ineffectiveness, rituximab was started. Anti-CCP and rheumatoid factor (RF) isotypes (IgM, IgA, IgG) levels were measured at entry, 12 months and again at 12 months after swapping to rituximab. RESULTS: After 1 year of therapy of the first biological drug, patients taking anti-TNF-alpha drugs showed a significant reduction of the anti-CCP levels (p=0.002), and all RF isotypes (p=0.003). Also patients treated with rituximab or tolicizumab had a significant decrease in anti-CCP (p=0.01) and RF isotype levels (p=0.01). Anti-CCP levels did not correlated with DAS28 over time. In patients switching to rituximab after failure of TNF-alpha blockers, anti-CCP levels did not change at 12 months (p=0.06), despite of the reduction of DAS28 (p=0.02) and RFs levels (p=0.02). CONCLUSIONS: Our study showed that anti-CCP levels may change during RA course, regardless of the biological drug used and the clinical response. PMID- 26885602 TI - Melanocytic Hyperplasia in the Epidermis Overlying Trichoblastomas in 100 Randomly Selected Cases. AB - One hundred cases of trichoblastomas (large nodular, small nodular, cribriform, lymphadenoma, and columnar) were randomly selected and studied for the presence of melanocytic hyperplasia in the epidermis overlying the tumors, which was defined as foci of increased melanocytes in the basal layer of the epidermis (more than 1 per 4 basal keratinocytes). Focal melanocytic hyperplasia was detected in a total of 22 cases of trichoblastoma (22%), and this phenomenon was most frequently seen in columnar trichoblastoma (7 cases), followed by large nodular trichoblastoma (5 cases). The mechanism of epidermal melanocytic hyperplasia overlying trichoblastoma is unclear. Ultraviolet may be a contributing factor, as focal melanocytic hyperplasia was also detected in one third of cases in the epidermis overlying uninvolved skin, usually associated with solar elastosis. This is further corroborated by the occurrence of the lesions predominantly on the face. Melanocytic hyperplasia overlying trichoblastoma appears to have no impact on the clinical appearance of the lesion and is recognized only microscopically. In an adequate biopsy specimen containing at least part of trichoblastoma, it should not cause any diagnostic problems. PMID- 26885603 TI - Systemic Hyalinosis With Heterozygous CMG2 Mutations: A Case Report and Review of Literature. AB - Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive disorder characterized by hyalinizing fibrosis of the skin and internal organs. Clinical features include multiple papular skin lesions, gingival hyperplasia, joint contractures, and osteolytic bone lesions. The systemic variant of JHF, known as infantile systemic hyalinosis (ISH), has an early onset and poor prognosis. Histological examination of cutaneous lesions shows bland-appearing fibroblasts within amorphous eosinophilic hyaline depositions. JHF and infantile systemic hyalinosis form a clinical spectrum with higher mortality that is typically observed in systemic cases. Here, the authors present a case of systemic hyalinosis with a heterozygous mutation in CMG2 that resulted in improved survival. PMID- 26885604 TI - Cold-Associated Perniosis of the Thighs ("Equestrian-Type" Chilblain): A Reappraisal Based on a Clinicopathologic and Immunohistochemical Study of 6 Cases. AB - Cold-associated perniosis of the thighs ("equestrian cold panniculitis") is an unusual and still enigmatic entity. The authors retrieved 6 cases for a re evaluation of their clinicopathologic features and for an immunohistochemical assessment with antibodies anti-CD3, anti-CD20, and anti-CD123. All patients were women, aged 17-45 years. One of them had elevated antinuclear antibody titers. Available anamnestic data confirmed the triggering role of prolonged/intermittent exposure to cold (not necessarily for equestrian activities). The lesions affected the thighs, with a preferential, although not exclusive involvement of the upper lateral surface. The histopathological pattern was perivascular, superficial, and deep, extending toward the superficial fat lobules, with lymphocytic vasculitis and mucin deposition; clumps of CD123 cells were found in 4 of 6 cases. Cold-associated perniosis of the thighs cannot be considered as a panniculitis. The histopathological features considerably overlap with perniosis at other sites of the body and with chilblain lupus erythematosus. PMID- 26885605 TI - Phenotypic Variation in Different Lesions of Mycosis Fungoides Biopsied Within a Short Period of Time From the Same Patient. AB - Phenotypic variants of mycosis fungoides (MF) include mainly the expression of cytotoxic markers by neoplastic cells (either alpha/beta or gamma/delta cytotoxic). To manage the patient properly, distinction from other cutaneous cytotoxic natural killer/T-cell lymphomas is paramount. Particularly for cutaneous gamma/delta T-cell lymphoma, distinction is often based on clinicopathologic correlation (presence of tumors at first diagnosis as opposed to patches only in MF). The authors report a case of cytotoxic MF characterized by expression of TCRgamma in two of three biopsies performed within a time frame of 1 week. The patient presented with patches, plaques, and 1 tumor at the time of first diagnosis; thus, distinction from cutaneous gamma/delta T-cell lymphoma was not possible on clinical grounds alone. The diagnosis of MF was established, thanks to the phenotypic variations revealed by the three biopsies, with 1 lacking expression of cytotoxic proteins (TIA-1 and granzyme B) and of TCRgamma. This case shows the importance to perform several biopsies in cases of cutaneous lymphoma, as morphologic and phenotypic features are variable and information gathered from a single biopsy may result in a wrong diagnosis. PMID- 26885606 TI - Malignant Clear Cell Acanthoma: Report of a Rare Case of Clear Cell Acanthoma Like Tumor With Malignant Features. AB - An erythematous and moist tumor nodule on the left temple of a 92-year-old woman was biopsied and identified as a clear cell acanthoma (CCA)-like tumor with malignant cytology and high proliferation activity. This case is similar to 2 cases reported previously as atypical CCA. The authors believe that these tumors are malignant counterparts of CCA and propose to call them malignant CCA. The clinicopathologic features of the present case are described along with dermoscopic findings. PMID- 26885607 TI - Clinical Features of Thoracic Spinal Stenosis-associated Myelopathy: A Retrospective Analysis of 427 Cases. AB - STUDY DESIGN: This was a retrospective review. OBJECTIVE: The aim of this study was to examine the epidemiological characteristics and causes of spinal cord compression in thoracic spinal stenosis (TSS). SUMMARY OF BACKGROUND DATA: As the thoracic spinal canal is relatively narrow and the thoracic cord has a poor blood supply, severe neurological symptoms may develop if TSS is not treated promptly. However, as it is rare, TSS is less often studied and its clinical features are often not recognized. METHODS: Between 2005 and 2012, 427 patients diagnosed with TSS underwent surgery in our department. The male to female ratio was 1.4:1. The mean age was 53 years. The most reported symptom was motor deficit in the lower extremities (347 cases, 81%), followed by sensory deficit in the lower limbs (271 cases, 64%). Falls were the most common trigger of acute symptoms (29 cases, 7%). Preoperative imaging results of each case were reviewed to summarize the causes and site of cord compression and coexisting spinal diseases. RESULTS: The most reported compressive factor was ossification of the ligamentum flavum (OLF), which implicated in 309 cases, followed by thoracic disk herniation (TDH) and ossification of the posterior longitudinal ligament (OPLL). The most common site of OLF and TDH was T9-L1 (56% and 89%, respectively), whereas OPLL was mainly found at T1-8 (90%). Forty-seven patients (11%) had coexisting lumbar spinal disease and 64 (15%) had cervical disease. CONCLUSIONS: Onset of TSS was generally insidious but may be triggered acutely by apparently trivial events. Myelopathy mainly affected the lower limbs. The most common cause was OLF in the lower thoracic spine. Cervical or lumbar spinal disease was often also evident; therefore, comprehensive clinical assessment is required to avoid delays in diagnosis and treatment. PMID- 26885608 TI - Hedgehog inhibitors selectively target cell migration and adhesion of mantle cell lymphoma in bone marrow microenvironment. AB - The clinical benefits of a Hedgehog (Hh) inhibitor, LDE225 (NPV-LDE-225, Erismodegib), have been unclear in hematological cancers. Here, we report that LDE225 selectively inhibited migration and adhesion of mantle cell lymphoma (MCL) to bone marrows via very late antigen-4 (VLA-4) mediated inactivation of focal adhesion kinase (FAK) signaling. LDE225 treatment not only affected MCL cells, but also modulated stromal cells within the bone marrow microenvironment by decreasing their production of SDF-1, IL-6 and VCAM-1, the ligand for VLA-4. Surprisingly, LDE225 treatment alone did not suppress cell proliferation due to increased CXCR4 expression mediated by reactive oxygen species (ROS). The increased ROS/CXCR4 further stimulated autophagy formation. The combination of LDE225 with the autophagy inhibitors further enhanced MCL cell death. Our data, for the first time, revealed LDE225 selectively targets MCL cells migration and adhesion to bone marrows. The ineffectiveness of LDE225 in MCL is due to autophagy formation, which in turn increases cell viability. Inhibiting autophagy will be an effective adjuvant therapy for LDE225 in MCL, especially for advanced MCL patients with bone marrow involvement. PMID- 26885610 TI - Comparison of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents: a pooled analysis and review. AB - Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the 'related articles' feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 (P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents. PMID- 26885609 TI - SIRT1 at the crossroads of AKT1 and ERbeta in malignant pleural mesothelioma cells. AB - In this report, we show that malignant pleural mesothelioma (MPM) patients whose tumors express high levels of AKT1 exhibit a significantly worse prognosis, whereas no significant correlation with AKT3 expression is observed. We provide data that establish a phosphorylation independent role of AKT1 in affecting MPM cell shape and anchorage independent cell growth in vitro and highlight the AKT1 isoform-specific nature of these effects.We describe that AKT1 activity is inhibited by the loss of SIRT1-mediated deacetylation and identify, by mass spectrometry, 11 unique proteins that interact with acetylated AKT1.Our data demonstrate a role of the AKT1/SIRT1/FOXM1 axis in the expression of the tumor suppressor ERbeta. We further demonstrate an inhibitory feedback loop by ERbeta, activated by the selective agonist KB9520, on this axis both in vitro and in vivo.Our data broaden the current knowledge of ERbeta and AKT isoform-specific functions that could be valuable in the design of novel and effective therapeutic strategies for MPM. PMID- 26885611 TI - Exosomes released by granulocytic myeloid-derived suppressor cells attenuate DSS induced colitis in mice. AB - Myeloid-derived suppressor cells (MDSC) have been described in inflammatory bowel disease (IBD), but their role in the disease remains controversial. We sought to define the effect of granulocytic MDSC-derived exosomes (G-MDSC exo) in dextran sulphate sodium (DSS)-induced murine colitis. G-MDSC exo-treated mice showed greater resistance to colitis, as reflected by lower disease activity index, decreased inflammatory cell infiltration damage. There was a decrease in the proportion of Th1 cells and an increase in the proportion of regulatory T cells (Tregs) in mesenteric lymph nodes (MLNs) from G-MDSC exo-treated colitis mice. Moreover, lower serum levels of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were detected in G-MDSC exo-treated colitis mice. Interestingly, inhibition of arginase (Arg)-1 activity in G-MDSC exo partially abrogated the spontaneous improvement of colitis. In addition, G-MDSC exo could suppress CD4+ T cell proliferation and IFN-gamma secretion in vitro and inhibit the delayed-type hypersensitivity (DTH) response, and these abilities were associated with Arg-1 activity. Moreover, G-MDSC exo promoted the expansion of Tregs in vitro. Taken together, these results suggest that G-MDSC exo attenuate DSS-induced colitis through inhibiting Th1 cells proliferation and promoting Tregs expansion. PMID- 26885613 TI - Long noncoding RNA Saf and splicing factor 45 increase soluble Fas and resistance to apoptosis. AB - In multicellular organisms, cell growth and differentiation is controlled in part by programmed cell death or apoptosis. One major apoptotic pathway is triggered by Fas receptor (Fas)-Fas ligand (FasL) interaction. Neoplastic cells are frequently resistant to Fas-mediated apoptosis, evade Fas signals through down regulation of Fas and produce soluble Fas proteins that bind FasL thereby blocking apoptosis. Soluble Fas (sFas) is an alternative splice product of Fas pre-mRNA, commonly created by exclusion of transmembrane spanning sequences encoded within exon 6 (FasDeltaEx6). Long non-coding RNAs (lncRNAs) interact with other RNAs, DNA, and proteins to regulate gene expression. One lncRNA, Fas antisense or Saf, was shown to participate in alternative splicing of Fas pre mRNA through unknown mechanisms. We show that Saf is localized in the nucleus where it interacts with Fas receptor pre-mRNA and human splicing factor 45 (SPF45) to facilitate alternative splicing and exclusion of exon 6. The product is a soluble Fas protein that protects cells against FasL-induced apoptosis. Collectively, these studies reveal a novel mechanism to modulate this critical cell death program by an lncRNA and its protein partner. PMID- 26885612 TI - BAP1 suppresses lung cancer progression and is inhibited by miR-31. AB - BRCA1-associated protein-1 (BAP1) is an important nuclear-localized deubiquitinating enzyme that serves as a tumor suppressor in lung cancer; however, its function and its regulation are largely unknown. In this study, we found that BAP1 protein levels were dramatically diminished in lung cancer tissues while its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism was involved in BAP1 regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that could potentially bind BAP1. We predicted and experimentally validated miR-31 as a direct regulator of BAP1. Moreover, we showed that miR-31 promoted proliferation and suppressed apoptosis in lung cancer cells and accelerated the development of tumor growth in xenograft mice by inhibiting BAP1. Taken together, this study highlights an important role for miR-31 in the suppression of BAP1 in lung cancer cells and may provide insights into the molecular mechanisms of lung carcinogenesis. PMID- 26885614 TI - MRTF/SRF dependent transcriptional regulation of TAZ in breast cancer cells. AB - Dysregulation of Hippo pathway results in activation of transcriptional co activators YAP/TAZ in breast cancer. Previously, we showed that overexpression of TAZ in breast cancer promotes cell migration, invasion and tumorigenesis. Here, we show that upregulation of TAZ in breast cancers could also be due to dysregulation of TAZ transcription. Heregulin beta1 (HRG1) increases TAZ mRNA level in breast cancer cells. TAZ is a direct target of MRTF/SRF transcriptional factors which are activated by HRG1. Both MRTF/SRF and TAZ are the important downstream effectors enhancing cell migration induced by HRG1. TAZ mRNA level is correlated with nuclear localization of MRTF in breast cancer cells and the mRNA level of MRTF/SRF direct target genes in breast cancers, indicating the correlation between MRTF/SRF activity and TAZ expression. Our results provide new insights into the transcriptional regulation of TAZ and dysregulation mechanism of TAZ in breast cancer, which could be a new therapeutic strategy for breast cancer. PMID- 26885616 TI - Predictive value of GGN and CAG repeat polymorphisms of androgen receptors in testicular cancer: a meta-analysis. AB - The risk of testicular cancer (TC) is markedly increased in subjects with androgen insensitivity, and previous studies have proposed that GGN and CAG repeats in androgen receptors (AR) could be related to the risk of TC. To evaluate the association between the length of GGN and CAG repeats in AR and TC, a meta-analysis involving 3255 TC cases and 2804 controls was performed. The results suggested that long GGN repeats are associated with an increased risk of TC compared with those < 23 [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.05-1.41]; similarly, a subgroup analysis revealed that this association occurred in studies with case sizes > 200, and in the mid-latitude, and seminoma subgroups. The subgroup analysis based on populations, high-latitude, and seminomas/non-seminomas suggested that AR CAG repeat polymorphisms with > 25 and < 21 + > 25 repeats might confer a protective effect to the patients with TC (in the high-latitude subgroup analysis, for > 25 vs. 21-25: OR = 0.54, 95% CI = 0.41 0.70). In contrast, an increased risk of TC was observed for AR CAG repeat polymorphisms with > 25 and < 21 + > 25 repeats in the mid-latitude subgroup (for > 25 vs. 21-25: OR = 1.65, 95% CI = 1.09-2.50). In addition, no associations between the remaining subgroups and male infertility were observed. In short, this meta-analysis suggested that AR GGN and CAG repeat polymorphisms may be involved in the etiology of TC. PMID- 26885615 TI - Combining FoxP3 and Helios with GARP/LAP markers can identify expanded Treg subsets in cancer patients. AB - Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3-Helios+ and activated FoxP3+/-Helios+ CD4+ T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3-LAP+ Tregs in non-activated and activated settings, and FoxP3+Helios+GARP+LAP+ activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP-/+LAP+ CD4+ T cells made IL-10, and not IFN-gamma, and levels of IL-10-secreting CD4+ T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker. PMID- 26885617 TI - Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer. AB - TEF3-1 (transcriptional enhancer factor 3 isoform 1), also known as TEAD4 (TEA domain family member 4), was recently revealed as an oncogenic character in cancer development. However, the underlying molecular pathogenic mechanisms remain undefined. In this paper, we investigated nuclear TEF3-1 could promote G1/S transition in HUVECs, and the expression levels of cyclins and CDKs were upregulated. Additionally, if TEF3-1 was knocked down, the expression of cyclins and CDKs was downregulated while the expression of P21, a negative regulator of the cell cycle, was upregulated. A microarray analysis also confirmed that TEF3-1 overexpression upregulates genes that are related to cell cycle progression and the promotion of angiogenesis. Moreover, we observed that nuclear TEF3-1 was highly expressed during the formation of vascular structures in gastric cancer (GC). Finally, tumor xenograft experiments indicated that, when TEF3-1 was knocked down, tumor growth and angiogenesis were also suppressed. Taken together, these results demonstrate for the first time that TEF3-1 localization to the nucleus stimulates the cell cycle progression in HUVECs and specifically contributes to tumor angiogenesis. Nuclear TEF3-1 in HUVECs may serve as an oncogenic biomarker, and the suppression of TEF3-1 may be a potential target in anti-tumor therapy. PMID- 26885618 TI - GADD45alpha and gamma interaction with CDK11p58 regulates SPDEF protein stability and SPDEF-mediated effects on cancer cell migration. AB - The epithelium-specific Ets transcription factor, SPDEF, plays a critical role in metastasis of prostate and breast cancer cells. While enhanced SPDEF expression blocks migration and invasion, knockdown of SPDEF expression enhances migration, invasion, and metastasis of cancer cells. SPDEF expression and activation is tightly regulated in cancer cells; however, the precise mechanism of SPDEF regulation has not been explored in detail. In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway. As a consequence of CDK11p58 mediated degradation of SPDEF, this loss of SPDEF protein results in increased prostate cancer cell migration and invasion. In contrast, knockdown of CDK11p58 protein expression by interfering RNA or SPDEF overexpression inhibit migration and invasion of cancer cells. We demonstrate that CDK11p58 mediated degradation of SPDEF is attenuated by Growth Arrest and DNA damage-inducible 45 (GADD45) alpha and , two proteins inducing G2/M cell cycle arrest. We show that GADD45 alpha and gamma, directly interact with CDK11p58 and thereby inhibit CDK11p58 activity, and consequentially SPDEF phosphorylation and degradation, ultimately reducing prostate cancer cell migration and invasion. Our findings provide new mechanistic insights into the complex regulation of SPDEF activity linked to cancer metastasis and characterize a previously unidentified SPDEF/CDK11p58/GADD45alpha/gamma pathway that controls SPDEF protein stability and SPDEF-mediated effects on cancer cell migration and invasion. PMID- 26885619 TI - MR imaging biomarkers for evaluating therapeutic effects shortly after near infrared photoimmunotherapy. AB - Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photon absorbers after irradiation with NIR light. The purpose of this study was to determine if MR imaging can detect changes in the MR properties of tumor within several hours of NIR-PIT. A431 cells were injected subcutaneously in the right and left dorsi of 12 mice. Six days later, the mice were injected with a photon absorber, IR700, conjugated to panitumumab, an antibody targeting epidermal growth factor receptor. One day later, only right sided tumor was exposed to NIR light (treated tumor). MRI was performed 1 day before and 1-2 hours after NIR-PIT using gadofosveset for six mice and gadopentetate dimeglumine for another six mice. T2 relaxation times, the apparent diffusion coefficient (ADC) for the following combinations of b-values: 0-1000, 200-1000 and 500-1000 s/mm2 and enhancement indices were compared before and after NIR-PIT using a two sided paired t-test. For treated tumors, T2 relaxation time increased after NIR PIT (p < 0.01) and all three ADC values decreased after NIR-PIT (p < 0.01). Moreover, the enhancement area under the curve (AUC) using gadofosveset increased after NIR-PIT (p = 0.02). In conclusion, prolongation of T2, reductions in ADC and increased enhancement using gadofosveset are seen within 2 hours of NIR-PIT treatment of tumors. Thus, MRI can be a useful imaging biomarker for detecting early therapeutic changes after NIR-PIT. PMID- 26885622 TI - Multiple Paternity in Urban Norway Rats: Extended Ranging for Mates. AB - Norway rats are an abundant synanthropic species in urban settings and serve as reservoirs for many pathogens. Attempts to control their populations have met with little success. Recent genetic studies suggest that local populations are structured and few individuals move significant distances, but there is substantial gene flow. To understand these observations and their implications on control strategies, we genotyped 722 rats from 20 alleys in Baltimore to establish paternity for 180 embryos. Up to 88 males may have contributed to the litters. All litters were sired by >=2 males, with an average of 4.9 (range 2-7) males. For dams and sires with known locations, most matings (71.7%; n = 46) occurred among animals from different alleys. The average distance between sires and dams was 114 meters (range 8-352 meters). In 10/17 (58.8%) litters, the majority of the identified sires were captured in different alleys than the females. Sires were significantly less related to females than were the males captured in the females' alleys. Although rats may generally restrict their movements, either receptive females and/or breeding males engage in mate-seeking behaviors that extend beyond movement patterns at other times. This geographically extends the sizes of local populations and buffers them from the impacts of control strategies that focus on local infestations. PMID- 26885623 TI - The Cure PSP Care Guide: A Telephonic Nursing Intervention for Individuals and Families Living With Progressive Supranuclear Palsy. AB - Progressive supranuclear palsy (PSP) is a rare, progressive, and terminal neurodegenerative disease characterized by problems with ambulation, balance, mobility, vision, speech, swallowing, and behavior during the 7- to 10-year course of the illness. Substantial evidence in the nursing literature supports the benefits of patient education, self-management, chronic disease management, telehealth, and nurse navigation programs, which enhance patient and caregiver knowledge, improve day-to-day management by developing an awareness of resources, decrease dependence on services, and address caregiver needs. The Cure PSP Care Guide is a targeted telehealth nursing intervention aimed at providing knowledge, guidance, and resources to the vulnerable individuals and families living with PSP; identifying local resources; and building community. During the course of two telephone calls, individuals and their caregivers are assessed to develop a Cure PSP Care Guide designed to provide guidance along the trajectory. A knowledge assessment, self-efficacy scale, and Caregiver Strain Index are administered before and after the intervention to determine the program intervention effect. Caregiver knowledge assessments improved after the intervention, whereas strain scores were static. Qualitative data show the ability of the intervention to address caregiver needs for knowledge and support, daily management tips, and resource identification. The preliminary quantitative and qualitative data collected on this pilot project justify further exploration of the use of telehealth to remotely deliver nurse case management to the vulnerable individuals and families living with PSP. PMID- 26885620 TI - Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence. AB - Our recent retrospective study revealed a significantly reduced risk of bladder cancer (BC) recurrence in men who received androgen deprivation therapy (ADT) for their prostate cancer. However, whether androgen receptor (AR) signals contributed to the preventive effect of ADT remained unclear because ADT could reduce serum estrogens as well. The purpose of this study is to investigate the associations between the expression of AR/estrogen receptors (ERs) and BC recurrence in patients treated with ADT. We immunohistochemically stained 72 BCs and 42 corresponding normal urothelial tissues. AR/ERalpha/ERbeta were positive in 44(61%)/22(31%)/39(54%) tumors and 35(83%)/24(57%)/34(81%) corresponding normal urothelial tissues, respectively. There were no statistically significant correlations between AR/ERalpha/ERbeta expression and clinicopathological features of BC. With a median follow-up of 31.3 months, 12 (43%) of 28 patients with AR-negative tumor versus 11 (23%) of 44 patients with AR-positive tumor experienced BC recurrence. Thus, patients with AR-positive tumor had a significantly lower risk of BC recurrence (P=0.031), compared with those with AR negative tumor. Meanwhile, the expression of ERalpha/ERbeta in tumors and that of AR/ERalpha/ERbeta in normal urothelial tissues were not significantly correlated with BC recurrence. A multivariate analysis revealed AR positivity in tumors as an independent prognosticator (hazard ratio: 0.27; 95% confidence interval: 0.11 0.67) for BC recurrence. These results indicate that ADT prevents BC recurrence via the AR pathway, but not via the ERalpha/ERbeta pathways. PMID- 26885621 TI - Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort. AB - There is a growing need for high throughput diagnostic tools for early diagnosis and treatment monitoring of prostate cancer (PCa) in Africa. The role of cancer testis antigens (CTAs) in PCa in men of African descent is poorly researched. Hence, we aimed to elucidate the role of 123 Tumour Associated Antigens (TAAs) using antigen microarray platform in blood samples (N = 67) from a South African PCa, Benign prostatic hyperplasia (BPH) and disease control (DC) cohort. Linear (fold-over-cutoff) and differential expression quantitation of autoantibody signal intensities were performed. Molecular signatures of candidate PCa antigen biomarkers were identified and analyzed for ethnic group variation. Potential cancer diagnostic and immunotherapeutic inferences were drawn. We identified a total of 41 potential diagnostic/therapeutic antigen biomarkers for PCa. By linear quantitation, four antigens, GAGE1, ROPN1, SPANXA1 and PRKCZ were found to have higher autoantibody titres in PCa serum as compared with BPH where MAGEB1 and PRKCZ were highly expressed. Also, p53 S15A and p53 S46A were found highly expressed in the disease control group. Statistical analysis by differential expression revealed twenty-four antigens as upregulated in PCa samples, while 11 were downregulated in comparison to BPH and DC (FDR = 0.01). FGFR2, COL6A1and CALM1 were verifiable biomarkers of PCa analysis using urinary shotgun proteomics. Functional pathway annotation of identified biomarkers revealed similar enrichment both at genomic and proteomic level and ethnic variations were observed. Cancer antigen arrays are emerging useful in potential diagnostic and immunotherapeutic antigen biomarker discovery. PMID- 26885624 TI - Identification of Novel Zoonotic Activity of Bartonella spp., France. AB - Certain Bartonella species are known to cause afebrile bacteremia in humans and other mammals, including B. quintana, the agent of trench fever, and B. henselae, the agent of cat scratch disease. Reports have indicated that animal-associated Bartonella species may cause paucisymptomatic bacteremia and endocarditis in humans. We identified potentially zoonotic strains from 6 Bartonella species in samples from patients who had chronic, subjective symptoms and who reported tick bites. Three strains were B. henselae and 3 were from other animal-associated Bartonella spp. (B. doshiae, B. schoenbuchensis, and B. tribocorum). Genomic analysis of the isolated strains revealed differences from previously sequenced Bartonella strains. Our investigation identifed 3 novel Bartonella spp. strains with human pathogenic potential and showed that Bartonella spp. may be the cause of undifferentiated chronic illness in humans who have been bitten by ticks. PMID- 26885625 TI - Different contributions of angiostatin and endostatin in angiogenesis impairment in systemic sclerosis: a cohort study. AB - OBJECTIVES: To determine the concentrations of circulating endostatin and angiostatin in patients with systemic sclerosis (SSc) and to assess its relationship to disease subsets, evolution phase, organ involvement and nailfold capillaroscopic changes. METHODS: Endostatin and angiostatin serum levels were measured by ELISA in a cohort of 57 patients with SSc, and correlated with disease subsets, evolution phase, organ involvement and nailfold capillaroscopic changes. RESULTS: Endostatin and angiostatin serum levels were significantly higher in patients with SSc than in healthy controls. Also, angiostatin was elevated in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc), but not in pre-SSc, while endostatin was increased in all SSc subsets. Moreover, endostatin was augmented in lcSSc, with or without CREST syndrome, whereas angiostatin was increased exclusively in patients with CREST. Analysis according to disease evolution phase found that endostatin was elevated in all phases while angiostatin was only significantly higher in intermediate and late phases of disease. Analysis regarding organ involvement revealed that angiostatin was significantly higher in patients with osteoarticular involvement and with more serious lung affection; no significant differences were found for endostatin. Finally, endostatin was significantly increased in all nailfold capillaroscopy stages, while angiostatin was only elevated in active and late phases. CONCLUSIONS: In accordance with previous studies, we found that endostatin and angiostatin concentrations are elevated in SSc patients. Additionally, we recognised the important role that endostatin might play as an early disease marker and realized that angiostatin is a marker of late disease and relates to lung disease severity. PMID- 26885626 TI - Probing dopants in wide semiconductor quantum point contacts. AB - Effects of randomly distributed impurities on conductance, spin polarization and electron localization in realistic gated semiconductor quantum point contacts (QPCs) have been simulated numerically. To this end density functional theory in the local spin-density approximation has been used. In the case when the donor layer is embedded far from the two-dimensional electron gas (2DEG) the electrostatic confinement potential exhibits the conventional parabolic form, and thus the usual ballistic transport phenomena take place both in the devices with split gates alone and with an additional metallic gate on the top. In the opposite case, i.e. when the randomly distributed donors are placed not far away from the 2DEG layer, there are drastic changes like the localization of electrons in the vicinity of confinement potential minima which give rise to fluctuations in conductance and resonances. The conductance as a function of the voltage applied to the top gate for asymmetrically charged split gates has been calculated. In this case resonances in conductance caused by randomly distributed donors are shifted and decrease in amplitude while the anomalies caused by interaction effects remain unmodified. It has been also shown that for a wide QPC the polarization can appear in the form of stripes. The importance of partial ionization of the random donors and the possibility of short range order among the ionized donors are emphasized. The motivation for this work is to critically evaluate the nature of impurities and how to guide the design of high-mobility devices. PMID- 26885627 TI - Modulating foveal representation can influence visual discrimination in the periphery. AB - A previous study by Williams et al. (2008) provided evidence for a novel form of feedback in the visual system, whereby peripheral information is contained in foveal retinotopic cortex. Beyond its possible implication for peripheral object recognition, few studies have examined the effect of a direct behavioral manipulation of the foveal feedback representation. To address this question, we measured participants' peripheral visual discrimination performance while modulating their foveal representation in a series of psychophysical experiments. On each trial, participants discriminated the identities of briefly presented novel, three-dimensional objects or the orientations of gratings in a peripheral location while fixating at the center. Besides the peripheral target, another stimulus (foil) was also presented and masked at the fovea. Our results showed that for objects, when the foveal foil that was identical to the peripheral target was presented 150 ms after the onset of the peripheral target, visual discrimination of the peripheral target was improved. This congruency effect occurred even though participants did not consciously perceive the foveal stimulus. No such effect was observed when the foveal foil was presented simultaneously with the peripheral target, or when the foil was presented in a parafoveal location. The foil effect in gratings was different from that in objects in terms of its effective timing and foveal specificity, suggesting that foveal feedback may be specific to high-level objects. These results indicate that modulating foveal information can affect individuals' ability to discriminate peripheral objects, suggesting a functional role of foveal representations in peripheral visual perception. PMID- 26885629 TI - Priming in a shape task but not in a category task under continuous flash suppression. AB - Continuous flash suppression (CFS) is an interocular suppression technique that uses high-contrast masks flashed to one eye to prevent conscious perception of images shown to the other eye. It has become widely used due to its strength and prolonged duration of suppression and its nearly deterministic control of suppression onset and offset. Recently, it has been proposed that action-relevant visual processing ascribed to the dorsal stream remains functional, while processing in the ventral stream is completely suppressed, when stimuli are invisible under CFS. Here we tested the hypothesis that the potentially dorsal stream-based analysis of prime-stimulus elongation during CFS affects the categorization of manipulable target objects. In two behavioral experiments, we found evidence for priming in a shape task, but none for priming in a category task, when prime stimuli were rendered invisible using CFS. Our results thus support the notion that the representation of CF-suppressed stimuli is more limited than previously thought. PMID- 26885630 TI - Functionalized C@TiO2 hollow spherical architecture for multifunctional applications. AB - Hierarchical anatase titania (TiO2) with a hollow spherical architecture decorated with functionalized carbon dots (C(F)@THS) was synthesized by a solvothermal decomposition of titanium(IV) isopropoxide (TTIP) in the presence of a solution mixture containing thiourea and citric acid. Interestingly, the concomitant presence of thiourea and citric acid has been found to be essential to obtain such hierarchical hollow architecture because individual constituents produced non-hollow spheres when hydrothermally treated with TTIP. The co existence of these two constituents also accelerates the growth of hollow spheres. BET surface area study of C(F)@THS revealed the existence of a slit like mesoporosity with a surface area value of 81 m(2) g(-1). Time dependent FESEM and TEM studies confirmed the formation of nanoflake like structures in the intermediate stages followed by the growth of a hollow spherical architecture. We proposed that these nanoflakes get accumulated on the bubble surface to form such hollow spherical morphology. The PL spectral study and Raman shift of the as prepared C(F)@THS confirmed the presence of functionalized graphitic C dots on the surface. A thorough XPS analysis was conducted to explore the nature and relative atomic concentration of the functional groups (-COOH, -CONH2, -NH2). This C(F)@THS sample showed very fast and selective dye (methylene blue and methyl violet) adsorption ability (even from a mixture of two different dye solutions) due to these delta-site containing functional groups on the surface. As C(F)@THS showed only two times reusability for adsorption, the dye adsorbed C(F)@THS was calcined at 450 degrees C in air to yield organic free anatase TiO2 hollow spheres (THS) with a retention of the original structure. THS was recycled as an efficient and a reusable photocatalyst (k = 9.36 * 10(-2) min(-1)) as well as a photoanode in dye sensitized solar cells (DSSCs) having Jsc value of 19.58 mA cm(-2) with overall efficiency of 6.48%. PMID- 26885628 TI - Degraded attentional modulation of cortical neural populations in strabismic amblyopia. AB - Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI-informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye. PMID- 26885631 TI - Incidence of Nephrogenic Systemic Fibrosis Using Gadobenate Dimeglumine in 1423 Patients With Renal Insufficiency Compared With Gadodiamide. AB - OBJECTIVE: The purpose of this study was to assess the incidence of nephrogenic systemic fibrosis (NSF) before and after educational interventions, implementation of a clinical screening process, and change to gadobenate dimeglumine in patients who had an estimated glomerular filtration rate (eGFR) of 30 mL/min per 1.72 m or less. METHODS: This is a Health Insurance Portability and Accountability Act compliant, institutional review board exempt study. Two periods were studied-July 2005 to June 2006, during which gadodiamide was utilized as our magnetic resonance (MR) contrast agent, and November 2006 to August 2014, during which gadobenate dimeglumine was used as our MR contrast agent in patients who had an eGFR 30 mL/min per 1.72 m or less. In addition to a change in the MR contrast agent, education of our staff physician to the risks of NSF with MR contrast agents and the implementation of a clinical screening process occurred. The rate of NSF before and after the interventions was compared using the chi test. RESULTS: There was a statistically significant difference in the incidence of NSF in patients with an eGFR 30 mL/min per 1.72 m or less between the 2 periods: July 2005 to June 2006, 6 of 246 patients were diagnosed with NSF (P < 0.001), versus November 2006 to August 2014, 0 of 1423 patients were diagnosed with NSF. CONCLUSIONS: Our data demonstrates a marked decrease in the incidence of NSF after education of our referring physicians, implementation of clinical screening process, and change to gadobenate dimeglumine from gadodiamide in patients with renal insufficiency. This approach potentially provides an acceptable risk-benefit profile for patients with renal insufficiency that required MR imaging for clinical care. PMID- 26885632 TI - Liver Imaging Reporting and Data System v2014 With Gadoxetate Disodium-Enhanced Magnetic Resonance Imaging: Validation of LI-RADS Category 4 and 5 Criteria. AB - OBJECTIVES: The aim of this study was to validate the Liver Imaging Reporting and Data System (LI-RADS) v2014 category 4 (LR-4) and 5 (LR-5) criteria on gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in patients with chronic liver disease. MATERIALS AND METHODS: Between January and December 2012, 300 patients with chronic liver disease who had hepatic nodules 3.0 cm or smaller at surveillance ultrasonography and gadoxetate disodium-enhanced MRI were included. LI-RADS category was retrospectively assigned to each nodule on MRI. Final diagnosis was assessed using pathologic diagnosis only (operation or core-needle biopsy) or pathologic and clinical diagnosis (marginal recurrence after treatment or a change in lesion size on follow-up imaging). To validate the LR-4 and LR-5 criteria, the sensitivity, positive predictive value (PPV), and false referral rate for diagnosing hepatocellular carcinoma were examined. RESULTS: Based on major imaging features only, 137 nodules were initially assigned as LR-3, but 133 (97.1%) were upgraded into LR-4 by the presence of ancillary features. Excluding the remaining 4 LR-3 and 3 LR-M nodules, we analyzed 379 nodules in 294 patients, consisting of 211 LR-4 and 168 LR-5 nodules. Using pathologic diagnosis only, the sensitivity and PPV with 95% confidence intervals (CIs) for LR-5 were higher than those for LR-4 (57.3% [50.6-63.7] vs 42.7% [36.3-49.4]; 94.6% [89.0-97.5] vs 82.0% [73.7-88.1]), with a lower false referral rate (5.4% [2.5-11.0] vs 18.0% [11.9-26.3]). Using pathologic and clinical diagnosis, PPV and 95% CI for LR-5 were higher than that for LR-4 (95.2% [90.7-97.7] vs 79.1% [73.1-84.1]), whereas sensitivity and 95% CI for LR-5 was similar to that for LR-4 (48.9% [43.6-54.3] vs 51.1% [45.7-56.4]). CONCLUSIONS: In patients with chronic liver disease, LR-5 criteria on gadoxetate disodium-enhanced MRI had excellent PPV for diagnosing hepatocellular carcinoma, whereas LR-4 criteria showed good PPV, but are only of limited use. PMID- 26885633 TI - Highly efficient CuxO/TiO2 catalysts: controllable dispersion and isolation of metal active species. AB - Porous Cu(x)O/TiO2 architectures with enhanced dispersion of the active phase are synthesized by a facile MOF-templated method. Such a unique composite would furnish excellent catalytic activity for CO oxidation under relatively mild conditions. PMID- 26885634 TI - Rumpel-Leede Phenomenon Associated With Tourniquet-like Forces of Baby Carriers in Otherwise Healthy Infants: Baby Carrier Purpura. PMID- 26885635 TI - Evidences of Changes in Surface Electrostatic Charge Distribution during Stabilization of HPV16 Virus-Like Particles. AB - The stabilization of human papillomavirus type 16 virus-like particles has been examined by means of different techniques including dynamic and static light scattering, transmission electron microscopy and electrophoretic mobility. All these techniques provide different and often complementary perspectives about the aggregation process and generation of stabilized virus-like particles after a period of time of 48 hours at a temperature of 298 K. Interestingly, static light scattering results point towards a clear colloidal instability in the initial systems, as suggested by a negative value of the second virial coefficient. This is likely related to small repulsive electrostatic interactions among the particles, and in agreement with relatively small absolute values of the electrophoretic mobility and, hence, of the net surface charges. At this initial stage the small repulsive interactions are not able to compensate binding interactions, which tend to aggregate the particles. As time proceeds, an increase of the size of the particles is accompanied by strong increases, in absolute values, of the electrophoretic mobility and net surface charge, suggesting enhanced repulsive electrostatic interactions and, consequently, a stabilized colloidal system. These results show that electrophoretic mobility is a useful methodology that can be applied to screen the stabilization factors for virus-like particles during vaccine development. PMID- 26885636 TI - Adaptations to Speed Endurance Training in Highly Trained Soccer Players. AB - PURPOSE: The present study examined whether a period of additional speed endurance training would improve intense intermittent exercise performance in highly trained soccer players during the season and whether the training changed aerobic metabolism and the level of oxidative enzymes in type I and type II muscle fibers. METHODS: During the last 9 wk of the season, 13 semiprofessional soccer players performed additional speed endurance training sessions consisting of two to three sets of 8-10 repetitions of 30-m sprints with 10 s of passive recovery (SET). Before and after SET, subjects completed a double-step exercise protocol that included transitions from standing to moderate-intensity running (~75% HRmax), followed by transitions from moderate- to high-intensity running (~90% HRmax) in which pulmonary oxygen uptake (VO2) was determined. In addition, the yo-yo intermittent recovery test level 1 was performed, and a muscle biopsy was obtained at rest. RESULTS: The yo-yo intermittent recovery test level 1 performance was 11.6% +/- 6.4% (mean +/- SD) better (2803 +/- 330 vs 3127 +/- 383 m, P < 0.05) after SET compared with before SET. In the transition from standing to moderate-intensity running, phase II pulmonary VO2 kinetics was 11.4% +/- 16.5% faster (P < 0.05), and the running economy at this intensity was 2.3% +/- 3.0% better (P < 0.05). These improvements were apparent despite the content of muscle proteins regulating oxidative metabolism (3-hydroxyacyl CoA dehydrogenase, COX IV, and OXPHOS), and capillarization was reduced (P < 0.05). The content of 3 hydroxyacyl CoA dehydrogenase and citrate synthase in type I and type II fibers did not change. CONCLUSION: In highly trained soccer players, additional speed endurance training is associated with an improved ability to perform repeated high-intensity work. To what extent the training-induced changes in VO2 kinetics and mechanical efficiency in type I fibers caused the improvement in performance warrants further investigation. PMID- 26885637 TI - Skeletal Muscle Erythropoietin Expression Is Responsive to Hypoxia and Exercise. AB - PURPOSE: Erythropoietin is responsible for regulating the growth and development of red blood cells. Reports conflict on whether skeletal muscle is able to produce erythropoietin and release it into circulation and if exercise affects this. We set out to determine how erythropoietin is regulated in skeletal muscle and to determine whether skeletal muscle-derived erythropoietin can stimulate erythropoiesis. METHODS: Using an in vitro approach, we exposed proliferating and differentiated skeletal muscle cells to various forms of exercise-induced physiological stimuli and measured erythropoietin gene expression. To understand if skeletal muscle cells were able to stimulate erythropoiesis, independent of other cell types found in skeletal muscle, we used myoblast-conditioned media to treat bone marrow and to measure erythropoiesis through flow cytometry. We also measured erythropoietin expression and hypoxia in mice subjected to an exercise protocol designed to induce skeletal muscle oxygen stress. RESULTS: Hypoxia increased erythropoietin expression in C2C12 myoblasts, myotubes, and primary myoblasts in vitro by 50% to 130%. Bone marrow treated with media conditioned with hypoxic myoblasts for 24 h increased the number of Ter-119-positive cells by 32%. An erythropoietin-neutralizing antibody prevented this increase. Compared with unexercised controls, exhaustive exercise increased skeletal muscle HIF1alpha levels by 50% and HIF2alpha levels by 20%. Moreover, exercised skeletal muscle erythropoietin expression was 70% higher. CONCLUSION: These results demonstrate that skeletal muscle produces erythropoietin in a hypoxia and HIF dependent manner and that hypoxia-treated muscle is capable of stimulating erythropoiesis in vitro. PMID- 26885639 TI - Correction: Quantification of the Blood Platelet Reactivity in the ADP-Induced Model of Non-Lethal Pulmonary Thromboembolism in Mice with the Use of Laser Doppler Flowmetry. PMID- 26885638 TI - Ovariectomized Highly Fit Rats Are Protected against Diet-Induced Insulin Resistance. AB - INTRODUCTION: In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR)). PURPOSE: This study determined whether OVX HCR rats remain protected with exposure to high fat diet (HFD) compared with OVX LCR rats. METHODS: Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice. RESULTS: Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1alpha), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05). CONCLUSION: After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This "physical activity compensation" likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats. PMID- 26885641 TI - Eight New Species of Charinus Simon, 1892 (Arachnida: Amblypygi: Charinidae) Endemic for the Brazilian Amazon, with Notes on Their Conservational Status. AB - Eight new species of Charinus Simon, 1892 are described for the Brazilian Amazon, from the states of Para (C. bichuetteae sp. n., C. bonaldoi sp. n., C. carajas sp. n., C. ferreus sp. n., C. guto sp. n. and C. orientalis sp. n.) and Amazonas (Charinus brescoviti sp. n. and C. ricardoi sp. n.). All new species can be differentiated from the other species of the genus by the number of pseudo articles in basitibia IV, the presence/absence of median eyes, and the shape of the female gonopod. Brazil now becomes the country with the largest diversity of Amblypygi in the world, with 25 known species. Half of the new species described here have a high degree of endangerment: C. bichuetteae sp. n. is threatened by the flood caused by the hydroelectric dam of Belo Monte, and C. carajas sp. n., C. ferreus sp. n. and C. orientalis sp. n. are endangered by the iron mining in Carajas municipality and surroundings. The Charinus species here described are endemic to the Amazon Region, so in order to assure their preservation, it is strongly recommended a special care with their habitats (type localities) which are facing increasing rates of destruction and deforestation. PMID- 26885642 TI - Erratum to: Dietary intake in Japanese patients with kidney transplantation. PMID- 26885640 TI - Multiscale Modeling in the Clinic: Drug Design and Development. AB - A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models. PMID- 26885644 TI - Characterization of MazF-Mediated Sequence-Specific RNA Cleavage in Pseudomonas putida Using Massive Parallel Sequencing. AB - Under environmental stress, microbes are known to alter their translation patterns using sequence-specific endoribonucleases that we call RNA interferases. However, there has been limited insight regarding which RNAs are specifically cleaved by these RNA interferases, hence their physiological functions remain unknown. In the current study, we developed a novel method to effectively identify cleavage specificities with massive parallel sequencing. This approach uses artificially designed RNAs composed of diverse sequences, which do not form extensive secondary structures, and it correctly identified the cleavage sequence of a well-characterized Escherichia coli RNA interferase, MazF, as ACA. In addition, we also determined that an uncharacterized MazF homologue isolated from Pseudomonas putida specifically recognizes the unique triplet, UAC. Using a real time fluorescence resonance energy transfer assay, the UAC triplet was further proved to be essential for cleavage in P. putida MazF. These results highlight an effective method to determine cleavage specificity of RNA interferases. PMID- 26885647 TI - Prediction of Phenotypic Effects of Variants Observed in LOC_Os04g36720 of FRO1 Gene in Rice (Oryza sativa L.). AB - In rice, ferric-chelate reductase-1 (FRO1) (LOC_Os04g36720) gene was present on chromosome number 4 and its beginning and ending coordinates where coding sequence lies are 22182599 and 22186943, respectively. It plays a vital role in metal homeostasis and iron transportation in plants. Based on the alignment results, location of single-nucleotide variants is located in open reading frame and their effects of variants were predicted using SIFT sequence tool. The non synonymous variants at position 342 and 436 lies in helical and coil parts of the protein, respectively, as predicted by Psi-pred server. PSI-Blast which resulted in significant hits and the most similar protein sequence (Accession ID: NP_001052896) with available sequence features displayed 100 % identity with query cover of 99 %. Results suggest the non-synonymous variant at position 436 (Accession ID: TBGI204002) lies in FAD-binding domain and nsSNV at position 342 (Accession ID: TBGI203998) lies in periphery of NADP. The SNPs were also analyzed for the deleterious effect by PANTHER subPSEC scores and I-mutant score, and it was postulated that SNPs would be hampering on biological as well as molecular function of FRO 1 gene of rice. A cutoff of -3 corresponds to a 50 % probability that a score is deleterious. From this, the probability that a given variant will cause a deleterious effect on protein function is estimated by P deleterious, such that a subPSEC score of -4 corresponds to a P deleterious of 0.79. Hence, to study the phenotypic consequences of variant TBGI204002, we performed comparative molecular docking studies of native modeled protein and protein with induced mutation as receptors and FAD as ligand to be utilized for binding. The docking process was performed by AutoDock 4.2 software with Lamarckian Genetic algorithm as computational algorithm. Results suggest binding energies are higher in case of mutation-induced protein which suggests presence of variant TBGI204002 enhances binding of FAD ligand at FAD-binding domain site. In case of TBGI203998, similar comparative docking procedure was performed with FAD as binding ligand, which suggests presence of variant does not impact FAD binding at the domain site. We revealed impact of SNPs on the protein structure and its function using sequence-based tools. PMID- 26885649 TI - Erratum to: 1-Year outcome of concomitant intracarpal lesions in patients with dislocated distal radial fractures: a systematic assessment of 78 distal radial fractures. PMID- 26885643 TI - Neuroendocrine Tumors of the Prostate: Emerging Insights from Molecular Data and Updates to the 2016 World Health Organization Classification. AB - Neuroendocrine neoplasms of the prostate represent a multifarious group of tumors that exist both in pure forms and associated with prostatic adenocarcinoma. Morphologically, neuroendocrine cells in prostate neoplasms can range from being indistinguishable from surrounding prostate adenocarcinoma cells to having high grade neuroendocrine appearances similar to neuroendocrine malignancies of other organs. On the molecular level, neuroendocrine malignancies arising in the setting of prostate adenocarcinoma have been the subject of a large amount of recent research, most of which has supported the conclusion that neuroendocrine malignancy within the prostate develops as a transdifferentiation from prostate adenocarcinoma. There has not, however, been substantial investigation into rare, pure neuroendocrine malignancies and the possibility that these tumors may have a different cell of origin and molecular genesis. Here, we discuss the morphologic spectrum of malignant neuroendocrine prostate neoplasms and review the most recent molecular data on the subject of malignant neuroendocrine differentiation in prostatic adenocarcinoma. In reflection of the most recent data, we also discuss diagnostic classification of prostate neuroendocrine tumors with reference to the 2016 World Health Organization (WHO) classification. We discuss the reporting of these tumors, placing emphasis on the differentiation between pure and mixed neuroendocrine malignancies so that, in the least, they can be easily identified for the purposes of future clinical and laboratory-based investigation. Finally, we suggest a designation for an unclassifiable (or not otherwise specified) high-grade neuroendocrine prostate malignancy whose features do not easily place it into one of the WHO diagnostic entities. PMID- 26885650 TI - Recent advances in the clinical management of giant cell arteritis and Takayasu arteritis. AB - PURPOSE OF REVIEW: This article critically reviews the advances in medical management of giant cell arteritis (GCA) and Takayasu arteritis (TAK) with a focus on recent developments in targeted biologic therapy. RECENT FINDINGS: The role of biologics in the treatment of large vessel vasculitis (LVV) is expanding. TNFalpha inhibitors appear to be effective in the treatment of TAK but have little benefit in GCA. Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA. Increasing observational evidence supports the use of interleukin-6 inhibitors in TAK. Based on a small open-label study, ustekinumab appears safe and potentially effective for refractory GCA. A possible role of B cell dysregulation may contribute to pathogenic mechanisms in LVV, but support for the use of B cell depleting therapy is limited. SUMMARY: Interleukin-6 inhibitors appear efficacious in the treatment of refractory cases of LVV; however, utility in newly diagnosed immunosuppressive-naive patients is less well established. Abatacept and ustekinumab are promising targets for therapy in LVV but further investigation is needed before routine use is considered. PMID- 26885645 TI - Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study. AB - BACKGROUND: During the last decade, the use of 5-aminolevulinic acid (5-ALA) has been steadily increasing in neurosurgery. The study's main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas' patients. METHODS: National, multicenter and prospective observational study. INCLUSION CRITERIA: authorized conditions of use of 5-ALA. EXCLUSION CRITERIA: contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities. RESULTS: Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%). Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance. CONCLUSION: In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as incomplete resection was not identified as a prognostic factor risk for death. Because optimal fluorescence was correlated to higher complete resection rate, further research is needed to identify patients (or tumors) with more surgery benefits when using the 5-ALA. PMID- 26885651 TI - Introduction to Endocrine Disrupting Chemicals--is it time to act? PMID- 26885654 TI - Predicting Essential Metabolic Genome Content of Niche-Specific Enterobacterial Human Pathogens during Simulation of Host Environments. AB - Microorganisms have evolved to occupy certain environmental niches, and the metabolic genes essential for growth in these locations are retained in the genomes. Many microorganisms inhabit niches located in the human body, sometimes causing disease, and may retain genes essential for growth in locations such as the bloodstream and urinary tract, or growth during intracellular invasion of the hosts' macrophage cells. Strains of Escherichia coli (E. coli) and Salmonella spp. are thought to have evolved over 100 million years from a common ancestor, and now cause disease in specific niches within humans. Here we have used a genome scale metabolic model representing the pangenome of E. coli which contains all metabolic reactions encoded by genes from 16 E. coli genomes, and have simulated environmental conditions found in the human bloodstream, urinary tract, and macrophage to determine essential metabolic genes needed for growth in each location. We compared the predicted essential genes for three E. coli strains and one Salmonella strain that cause disease in each host environment, and determined that essential gene retention could be accurately predicted using this approach. This project demonstrated that simulating human body environments such as the bloodstream can successfully lead to accurate computational predictions of essential/important genes. PMID- 26885652 TI - [Subintimal recanalization. Indications, technique and results]. AB - CLINICAL/METHODICAL ISSUE: This article gives an overview of the current importance of so-called subintimal recanalization in the lower extremities. STANDARD RADIOLOGICAL METHODS: The primary technical goal of endovascular interventions in the lower extremities is the endoluminal restoration of blood circulation from the iliac arteries into the feet. METHODICAL INNOVATIONS: If endoluminal recanalization of e.g. high-grade flow-relevant stenoses or chronic total occlusion (CTO) is technically not possible, subintimal recanalization is a promising option and the only remaining minimally invasive alternative. During subintimal recanalization a channel is intentionally generated in the vessel wall (dissection) in order to bypass e. g. a chronic vascular occlusion over as short a distance as possible. PERFORMANCE: The technical success rate for subintimal recanalization of CTO of the lower extremities is 65-100 %. Technical failure occurs in approximately 25 % using the catheter and wire technique and is caused in most cases by difficulties in reaching the true lumen after the subintimal passage (the so-called re-entry). ACHIEVEMENTS: Compared to conventional subintimal recanalization, in recent years so-called re-entry devices have expanded the technical possibilities and depending on the medical experience and training level of the physician, provide an improvement in the technical success rate, a lower complication rate, a reduction of fluoroscopy time and the amount of necessary contrast medium but also result in higher costs. PRACTICAL RECOMMENDATIONS: Subintimal recanalization, whether carried out conventionally with a catheter and wire or using re-entry devices, of high-grade stenoses or CTO in the lower extremities provides a high technical success rate but requires an experienced and trained physician who is capable of operating the elaborate materials and mastering any possible complications. PMID- 26885655 TI - Ultrasound Assisted Extraction of Phenolic Compounds from Peaches and Pumpkins. AB - The ultrasound-assisted extraction (UAE) method was used to optimize the extraction of phenolic compounds from pumpkins and peaches. The response surface methodology (RSM) was used to study the effects of three independent variables each with three treatments. They included extraction temperatures (30, 40 and 50 degrees C), ultrasonic power levels (30, 50 and 70%) and extraction times (10, 20 and 30 min). The optimal conditions for extractions of total phenolics from pumpkins were inferred to be a temperature of 41.45 degrees C, a power of 44.60% and a time of 25.67 min. However, an extraction temperature of 40.99 degrees C, power of 56.01% and time of 25.71 min was optimal for recovery of free radical scavenging activity (measured by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) reduction). The optimal conditions for peach extracts were an extraction temperature of 41.53 degrees C, power of 43.99% and time of 27.86 min for total phenolics. However, an extraction temperature of 41.60 degrees C, power of 44.88% and time of 27.49 min was optimal for free radical scavenging activity (judged by from DPPH reduction). Further, the UAE processes were significantly better than solvent extractions without ultrasound. By electron microscopy it was concluded that ultrasonic processing caused damage in cells for all treated samples (pumpkin, peach). However, the FTIR spectra did not show any significant changes in chemical structures caused by either ultrasonic processing or solvent extraction. PMID- 26885653 TI - [Drug-coated balloons in the treatment of peripheral artery disease (PAD). History and current level of evidence]. AB - BACKGROUND: Despite initially encouraging technical success after femoropopliteal PTA, restenosis remains the major challenge in patients with peripheral artery disease (PAD). The main cause of restenosis is neointimal hyperplasia which can be suppressed by antiproliferative drugs. Drug-coated balloons (DCB) or drug eluting stents (DES) are used for the inhibition of restenosis. OBJECTIVES: The present article gives an overview of DCB development, actual DCB systems for femoro- and infrapopliteal use, displays the outcomes of randomized clinical trials and the discusses the evidence for the DCB treatment in PAD. METHODS: A systematic literature search was performed in i) medical journals (i. e. MEDLINE), ii) in international registers for clinical studies (i. e. www.clinicaltrials.gov ) and in iii) scientific session abstracts. RESULTS: The clinical evidence of the PTX-DCB of the first and following generation has been shown in several controlled randomized trials. CONCLUSIONS: Major advantages of the DCBs lie in leaving no stent scaffold behind, the immediate release of high drug concentrations with a single dosage, their efficacy in areas, where stents have been contra-indicated until now and its use for secondary interventions. As their effect seems to be limited in severely calcified lesions, prior plaque preconditioning or removal could be advantageous. First positive results data supporting this hypothesis do exist. PMID- 26885656 TI - Hemodynamic monitoring in the era of digital health. AB - Digital innovations are changing medicine, and hemodynamic monitoring will not be an exception. Five to ten years from now, we can envision a world where clinicians will learn hemodynamics with simulators and serious games, will monitor patients with wearable or implantable sensors in the hospital and after discharge, will use medical devices able to communicate and integrate the historical, clinical, physiologic and biological information necessary to predict adverse events, propose the most rationale therapy and ensure it is delivered properly. Considerable intellectual and financial investments are currently made to ensure some of these new ideas and products soon become a reality. PMID- 26885658 TI - Reservoir Sedimentation and Upstream Sediment Sources: Perspectives and Future Research Needs on Streambank and Gully Erosion. AB - The future reliance on water supply and flood control reservoirs across the globe will continue to expand, especially under a variable climate. As the inventory of new potential dam sites is shrinking, construction of additional reservoirs is less likely compared to simultaneous flow and sediment management in existing reservoirs. One aspect of this sediment management is related to the control of upstream sediment sources. However, key research questions remain regarding upstream sediment loading rates. Highlighted in this article are research needs relative to measuring and predicting sediment transport rates and loading due to streambank and gully erosion within a watershed. For example, additional instream sediment transport and reservoir sedimentation rate measurements are needed across a range of watershed conditions, reservoir sizes, and geographical locations. More research is needed to understand the intricate linkage between upland practices and instream response. A need still exists to clarify the benefit of restoration or stabilization of a small reach within a channel system or maturing gully on total watershed sediment load. We need to better understand the intricate interactions between hydrological and erosion processes to improve prediction, location, and timing of streambank erosion and failure and gully formation. Also, improved process-based measurement and prediction techniques are needed that balance data requirements regarding cohesive soil erodibility and stability as compared to simpler topographic indices for gullies or stream classification systems. Such techniques will allow the research community to address the benefit of various conservation and/or stabilization practices at targeted locations within watersheds. PMID- 26885657 TI - The novel pyrrolo-1,5-benzoxazepine, PBOX-15, synergistically enhances the apoptotic efficacy of imatinib in gastrointestinal stromal tumours; suggested mechanism of action of PBOX-15. AB - The C-KIT receptor tyrosine kinase is constitutively activated in the majority of gastrointestinal stromal tumours (GIST). Imatinib (IM) a selective inhibitor of C KIT, is indicated for the treatment of KIT-positive unresectable and/or metastatic GIST, and has tripled the survival time of patients with metastatic GIST. However, the majority of patients develop IM-resistance and progress. Although IM elicits strong antiproliferative effects, it fails to induce sufficient levels of apoptosis; acquired IM-resistance and disease recurrence remain an issue, a more effective drug treatment is greatly needed. We examined the effect of a novel microtubule-targeting agent (MTA), pyrrolo-1,5 benzoxazepine (PBOX)-15 in combination with IM on GIST cells. PBOX-15 decreased viability and in combination with IM synergistically enhanced apoptosis in both IM-sensitive and IM-resistant GIST cells, decreased the anti-apoptotic protein Mcl-1, and enhanced activation of pro-caspase-3 and PARP cleavage. The combination treatment also led to an enhanced inhibition of C-KIT-phosphorylation and inactivation of C-KIT-dependent signalling in comparison to either drug alone; CDC37, a key regulator of C-KIT in GIST was also dramatically decreased. Furthermore, PBOX-15 reduced CKII expression, an enzyme which regulates the expression of CDC37. In conclusion, our findings indicate the potential of PBOX 15 to improve the apoptotic response of IM in GIST cells and provide a more effective treatment option for GIST patients. PMID- 26885659 TI - Nonadherence to immunosuppressive therapy in kidney transplant recipients: can technology help? AB - End-stage kidney disease is a life-threatening condition that compels patients to accept either dialysis or transplant. Kidney transplantation is the best choice for patients with end-stage kidney disease because it ensures higher quality of life and longer survival rates than other choices, with less cost for the healthcare system. However, in order for renal recipients to maintain the functioning graft they must take lifelong immunosuppressive medications, with possible side effects and low medication adherence. It is known that low medication adherence in kidney transplant recipients may cause poor outcomes, chronic graft rejection, and graft failure. In this review, the authors give an overview of nonadherence in the transplant setting. In addition, they analyze the role of different technologies as an aid to improve adherence, with a focus on mobile-phone based solutions to monitor and enhance kidney transplant recipient compliance. PMID- 26885661 TI - Macroscopic morphology for estimation of malignant potential in pancreatic neuroendocrine neoplasm. AB - PURPOSE: Pancreatic neuroendocrine neoplasm (Pan-NEN) representing approximately 1.3 % of pancreatic malignancy cases in incidence has been a so rare disease that it remains major problem to analyze the malignant potential. The aim of this study was to verify whether the macroscopic morphology of Pan-NEN, a novel pathological classification, contributes to malignant potential. METHODS: From a total of 86 patients with Pan-NEN, 41 surgical sections obtained from the primary site were classified by their morphology into a simple nodular (SN) group and a non-SN group. The non-SN group was further divided into three subtypes: simple nodular with extranodular growth (SNEG), confluent multinodular (CM), and infiltrative (IF). The clinicopathological features of the SN and the non-SN groups were retrospectively compared. RESULTS: Overall 5-year survival rates with and without surgical resection were 94 and 48 %, respectively. SN and non-SN types were identified in 21 and 20 patients, respectively. The non-SN group comprised 14 SNEG type, 2 CM type, and 4 IF type. Synchronous lymph node metastases (p = 0.009), synchronous liver metastases (p = 0.048), microinvasion to an adjacent organ (p < 0.001), vascular invasion (p = 0.023), and neural invasion (p = 0.019) were more significant in the non-SN group than in the SN group. As judged by WHO 2004 classification and TNM stages (AJCC and ENETS), non SN type showed malignant trend (p < 0.05). Moreover, overall 5-year survival rates of SN and non-SN groups were 100 and 84.4 %, respectively (p = 0.048). CONCLUSIONS: Non-SN tumors may have higher malignant potential than SN tumors. PMID- 26885662 TI - Prospective assessment of time-dependent changes in quality of life of Japanese patients with prostate cancer following robot-assisted radical prostatectomy. AB - The objective of this study was to characterize changes in the quality of life (QOL) of Japanese patients following robot-assisted radical prostatectomy (RARP). This study included 298 consecutive localized prostate cancer (PC) patients undergoing RARP. The health-related QOL and disease-specific QOL were assessed using The Medical Outcomes Study 8-Item Short Form (SF-8) and The Extended Prostate Cancer Index Composite (EPIC), respectively, before and 1, 3, 6, 12 and 24 months after RARP. At 1 month after RARP, four (physical function, role limitations because of physical health problems, social function and role limitations because of emotional problems) of the eight scores in SF-8 were significantly impaired compared with those of baseline scores. However, all eight scores on all postoperative assessments, except for at 1 month after RARP, showed no significant differences from baseline scores. Although there were no significant differences in the bowel function, bowel bother, sexual bother, hormonal function or hormonal bother between baseline and postoperative assessments of EPIC at all time points, the urinary function, urinary incontinence and sexual function scores at 1, 3 and 6 months after RARP were significantly inferior to those of baseline scores, and urinary bother and urinary irritation/obstruction scores at 1 month after RARP were significantly impaired compared with those of baseline scores. These findings suggest that the health-related QOL of Japanese PC patients undergoing RARP may not be markedly deteriorated following RARP; however, as for the disease-specific QOL, urinary and sexual functions, particularly those early after RARP, appeared to be significantly impaired. PMID- 26885663 TI - Functional Characterization of the Tau Class Glutathione-S-Transferases Gene (SbGSTU) Promoter of Salicornia brachiata under Salinity and Osmotic Stress. AB - Reactive oxygen or nitrogen species are generated in the plant cell during the extreme stress condition, which produces toxic compounds after reacting with the organic molecules. The glutathione-S-transferase (GST) enzymes play a significant role to detoxify these toxins and help in excretion or sequestration of them. In the present study, we have cloned 1023 bp long promoter region of tau class GST from an extreme halophyte Salicornia brachiata and functionally characterized using the transgenic approach in tobacco. Computational analysis revealed the presence of abiotic stress responsive cis-elements like ABRE, MYB, MYC, GATA, GT1 etc., phytohormones, pathogen and wound responsive motifs. Three 5'-deletion constructs of 730 (GP2), 509 (GP3) and 348 bp (GP4) were made from 1023 (GP1) promoter fragment and used for tobacco transformation. The single event transgenic plants showed notable GUS reporter protein expression in the leaf tissues of control as well as treated plants. The expression level of the GUS gradually decreases from GP1 to GP4 in leaf tissues, whereas the highest level of expression was detected with the GP2 construct in root and stem under control condition. The GUS expression was found higher in leaves and stems of salinity or osmotic stress treated transgenic plants than that of the control plants, but, lower in roots. An efficient expression level of GUS in transgenic plants suggests that this promoter can be used for both constitutive as well as stress inducible expression of gene(s). And this property, make it as a potential candidate to be used as an alternative promoter for crop genetic engineering. PMID- 26885665 TI - Proteinaceous Pheromone Homologs Identified from the Cloacal Gland Transcriptome of a Male Axolotl, Ambystoma mexicanum. AB - Pheromones play an important role in modifying vertebrate behavior, especially during courtship and mating. Courtship behavior in urodele amphibians often includes female exposure to secretions from the cloacal gland, as well as other scent glands. The first vertebrate proteinaceous pheromone discovered, the decapeptide sodefrin, is a female attracting pheromone secreted by the cloacal gland of male Cynops pyrrhogaster. Other proteinaceous pheromones in salamanders have been shown to elicit responses from females towards conspecific males. The presence and levels of expression of proteinaceous pheromones have not been identified in the family Ambystomatidae, which includes several important research models. The objective of this research was therefore to identify putative proteinaceous pheromones from male axolotls, Ambystoma mexicanum, as well as their relative expression levels. The results indicate that axolotls possess two different forms of sodefrin precursor-like factor (alpha and beta), as well as a putative ortholog of plethodontid modulating factor. The beta form of sodefrin precursor-like factor was amongst the most highly expressed transcripts within the cloacal gland. The ortholog of plethodontid modulating factor was expressed at a level equivalent to the beta sodefrin precursor-like factor. The results are from a single male axolotl; therefore, we are unable to assess how representative our results may be. Nevertheless, the presence of these highly expressed proteinaceous pheromones suggests that male axolotls use multiple chemical cues to attract female conspecifics. Behavioral assays would indicate whether the putative protein pheromones elicit courtship activity from female axolotls. PMID- 26885666 TI - Registered report: Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. AB - The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from "Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF" by Heidorn and colleagues, published in Cell in 2010 (Heidorn et al., 2010). The experiments to be replicated are those reported in Figures 1A, 1B, 3A, 3B, and 4D. Heidorn and colleagues report that paradoxical activation of the RAF RAS-MEK-ERK pathway by BRAF inhibitors when applied to BRAF(WT) cells is a result of BRAF/CRAF heterodimer formation upon inactivation of BRAF kinase activity, and occurs only in the context of active RAS. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange, and the results of the replications will be published by eLife. PMID- 26885668 TI - Role of Fanconi anemia/BRCA pathway genes in hepatocellular carcinoma chemoresistance. AB - AIM: To investigate the expression of DNA repair genes and the impact of the breast cancer 1, early onset (BRCA1) protein on chemoresistance of hepatocellular carcinoma (HCC). METHODS: Microarray gene expression datasets were analyzed using the gene set enrichment analysis method. BRCA1 protein was tested by Western blotting. Response of HCC cells to interstrand cross-links was investigated by cell viability assay following exposure to mitomycin C, cisplatin, and melphalan. Effects of BRCA1 ectopic expression were studied in HepG2 cells with BRCA1 expression plasmids. Effects of BRCA1 downregulation were studied in SNU449 cells with BRCA1-specific siRNAs. Response of transfected SNU449 cells to mitomycin C was analyzed by cell viability tests and cell cycle analysis using flow cytometry. RESULTS: Expression of Fanconi anemia and double-stranded DNA break repair genes was significantly upregulated in HCC tumors. This upregulation displayed a gradual amplification during tumor progression. BRCA1 and BRCA2 genes were among consistently upregulated genes. Epithelial-like HCC cells had low BRCA1 expression and low chemoresistance, whereas mesenchymal-like HCC cells had high BRCA1 expression and increased chemoresistance. Ectopic expression of BRCA1 increased the chemoresistance of epithelial-like HepG2 cells. Conversely, BRCA1 knockdown chemosensitized mesenchymal-like SNU449 cells. Chemosensitization of SNU449 cells was due to cell cycle arrest at 4N stage. CONCLUSION: Increased expression of Fanconi anemia and double-stranded DNA repair genes such as BRCA1 is a novel mechanism of HCC chemoresistance. However, functional inactivation of BRCA1 expression is sufficient to reverse such chemoresistance. PMID- 26885664 TI - Omega-3 fatty acids as an adjunct for periodontal therapy-a review. AB - OBJECTIVES: The aim of this article is to present an overview of omega-3 fatty acids, their anti-inflammatory properties and potential use as an adjunct for periodontal therapy. MATERIALS AND METHODS: A general literature search was conducted to provide an overview of omega-3 fatty acids, their metabolism and anti-inflammatory properties. A more specific literature search of PubMed and EMBASE was conducted to identify articles dealing studies investigating the effects of omega-3 fatty acids in the treatment of periodontitis in animals and humans and included cross-sectional, longitudinal and intervention designs. RESULTS: To date, there is good emerging evidence that dietary supplementation with fish oil may be of some benefit and this is enhanced if combined with aspirin. All clinical intervention studies to date have been on small sample sizes, and this indicates there is need for larger and more robust clinical trials to verify these initial findings. CONCLUSIONS: Dietary supplementation with fish oil could be a cost-effective adjunctive therapy to the management of periodontal disease. CLINICAL RELEVANCE: The host modulatory properties of omega 3 fatty acids warrant further assessment of their use as an adjunct in the management of periodontitis. PMID- 26885669 TI - The promise and perils of big data in healthcare. PMID- 26885670 TI - Longitudinal adherence to colorectal cancer screening guidelines. AB - OBJECTIVES: To describe adherence with United States Preventive Services Task Force (USPSTF) colorectal cancer (CRC) screening recommendations over a 10-year period in a large, continuously insured screening population at average risk for CRC. STUDY DESIGN: Retrospective claims database analysis. METHODS: Insured members (N = 151,638) who turned 50 years old between January 1, 2000, and December 31, 2004, and were at average risk for CRC were included in the analysis. Subjects were categorized as adherent, inadequately screened, or screening-naive based on their level of adherence with USPSTF CRC screening guidelines. Outcomes considered were age at initial CRC screening and CRC screening tests received over the 10-year period. RESULTS: Of the 151,638 subjects in the cohort, only 97,518 (64%) were adherent with current CRC screening recommendations. An additional 18,050 (12%) were considered inadequately screened and 36,070 (24%) were screening-naive. In those subjects who received some form of CRC screening, the average age at screening initiation was 53 years--3 years past the age recommended by current guidelines. Of those subjects who were inadequately screened, nearly half (46%) received only 1 fecal occult blood or fecal immunochemical test over the 10-year period. CONCLUSIONS: In a sample of continuously insured average-risk individuals aged 50 to 54 years, CRC screening was initiated later and performed less frequently than recommended in USPSTF guidelines. PMID- 26885671 TI - The value of value-based insurance design: savings from eliminating drug co payments. AB - OBJECTIVES: To estimate the cost impact of a $0 co-pay prescription drug program implemented by a large healthcare employer as a part of its employee wellness program. STUDY DESIGN: A $0 co-pay program that included approximately 200 antihypertensive, antidiabetic, and antilipid medications was offered to Geisinger Health System (GHS) employees covered by Geisinger Health Plan (GHP) in 2007. Claims data from GHP for the years 2005 to 2011 were obtained. The sample was restricted to continuously enrolled members with Geisinger primary care providers throughout the study period. METHODS: The intervention group, defined as 2251 GHS employees receiving any of the drugs eligible for $0 co-pay, was propensity score matched based on 2 years of pre-intervention claims data to a comparison group, which was defined as 3857 non-GHS employees receiving the same eligible drugs at the same time. Generalized linear models were used to estimate differences in terms of per-member-per-month (PMPM) claims amounts related to prescription drugs and medical care. RESULTS: Total healthcare spending (medical plus prescription drug spending) among the GHS employees was lower by $144 PMPM (13%; 95% CI, $38-$250) during the months when they were taking any of the eligible drugs. Considering the drug acquisition cost and the forgone co-pay, the estimated return on investment over a 5-year period was 1.8. CONCLUSIONS: This finding suggests that VBID implementation within the context of a wider employee wellness program targeting the appropriate population can potentially lead to positive cost savings. PMID- 26885672 TI - Characterizing health plan price estimator tools: findings from a national survey. AB - OBJECTIVES: Policy makers have growing interest in price transparency and in the kinds of tools available to consumers. Health plans have implemented price estimator tools that make provider pricing information available to members; however, systematic data on prevalence and characteristics of such tools are limited. The purpose of this study was to describe the characteristics of price estimator tools offered by health plans to their members and to identify potential trends, challenges, and opportunities for advancing the utility of these tools. STUDY DESIGN: National Web-based survey. METHODS: Between 2014 and 2015, we conducted a national Web-based survey of health plans with commercial enrollment (100 plans, 43% response rate). Descriptive analyses were conducted using survey data. RESULTS: Health plan members have access to a variety of price estimator tool capabilities for commonly used procedures. These tools take into account member characteristics, including member zip code and benefit design. Despite outreach to members, however, challenges remain with respect to member uptake of such tools. CONCLUSIONS: Our study found that health plans share price and provider performance data with their members. PMID- 26885673 TI - Continuity of care and changes in medication adherence among patients with newly diagnosed diabetes. AB - OBJECTIVES: Recent studies have revealed significant variation in medication adherence among patients with chronic conditions. Little is known about the effect of continuity of care (COC) on changes in medication adherence. This study aims to identify medication adherence trajectories among patients with newly diagnosed diabetes, as well as to examine the association of COC and medication adherence among various adherence trajectories. METHODS: This study utilized a longitudinal design with a 6-year follow-up, from 2002 to 2008, under a universal health insurance program in Taiwan. Subjects 18 years or older with type 2 diabetes that was newly diagnosed in 2002 were included in the study. The main outcome was medication adherence measured by medication possession ratio each year. Group-based trajectory models were used for analysis. RESULTS: Four medication adherence trajectories were identified: persistent adherence (39.9%), increasing adherence (27.5%), decreasing adherence (12.0%), and nonadherence (20.6%). Patients with high or medium COC index scores were more likely to be adherent to medications than those with low COC index scores in all of the trajectory adherence groups. CONCLUSIONS: This study demonstrated the heterogeneity in patients' medication adherence and identified 4 distinct trajectories of medication adherences among those with newly diagnosed type 2 diabetes. Improving COC may lead to better medication adherence in all of the adherence trajectory groups. PMID- 26885667 TI - Activation of the Nrf2 Cell Defense Pathway by Ancient Foods: Disease Prevention by Important Molecules and Microbes Lost from the Modern Western Diet. AB - The Nrf2 (NFE2L2) cell defense pathway protects against oxidative stress and disorders including cancer and neurodegeneration. Although activated modestly by oxidative stress alone, robust activation of the Nrf2 defense mechanism requires the additional presence of co-factors that facilitate electron exchange. Various molecules exhibit this co-factor function, including sulforaphane from cruciferous vegetables. However, natural co-factors that are potent and widely available from dietary sources have not been identified previously. The objectives of this study were to investigate support of the Nrf2 cell defense pathway by the alkyl catechols: 4-methylcatechol, 4-vinylcatechol, and 4 ethylcatechol. These small electrochemicals are naturally available from numerous sources but have not received attention. Findings reported here illustrate that these compounds are indeed potent co-factors for activation of the Nrf2 pathway both in vitro and in vivo. Each strongly supports expression of Nrf2 target genes in a variety of human cell types; and, in addition, 4-ethylcatechol is orally active in mice. Furthermore, findings reported here identify important and previously unrecognized sources of these compounds, arising from biotransformation of common plant compounds by lactobacilli that express phenolic acid decarboxylase. Thus, for example, Lactobacillus plantarum, Lactobacillus brevis, and Lactobacillus collinoides, which are consumed from a diet rich in traditionally fermented foods and beverages, convert common phenolic acids found in fruits and vegetables to 4-vinylcatechol and/or 4-ethylcatechol. In addition, all of the alkyl catechols are found in wood smoke that was used widely for food preservation. Thus, the potentially numerous sources of alkyl catechols in traditional foods suggest that these co-factors were common in ancient diets. However, with radical changes in food preservation, alkyl catechols have been lost from modern foods. The absence of alkyl catechols from the modern Western diet suggests serious negative consequences for Nrf2 cell defense, resulting in reduced protection against multiple chronic diseases associated with oxidative stress. PMID- 26885674 TI - Global Progress and Challenges in Implementing New Medications for Treating Multidrug-Resistant Tuberculosis. AB - Two new drugs-bedaquiline and delamanid-have recently been approved by stringent regulatory authorities to treat multidrug-resistant tuberculosis (TB) and recommended by the World Health Organization for use under defined programmatic conditions. Introducing the medications in TB programs worldwide has not kept pace with the need for these drugs. In response, the DR-TB STAT (Drug-Resistant TB Scale-up Treatment Action Team) task force was formed in April 2015 to monitor progress and help overcome challenges. Information was collected from multiple sources and assessed monthly. Some progress has been made in introducing bedaquiline: as of October 2015, a total of 1,258 persons were on the medication under programmatic conditions. For delamanid, >100 patients, but few under programmatic conditions, have received the medication. Coordinated global action might help assist making these medications accessible for persons who need them most. PMID- 26885676 TI - The interplay of Escherichia coli O157:H7 and commensal E. coli: the importance of strain-level identification. PMID- 26885677 TI - Surgical Site Infection Rates in Seven Cities in Vietnam: Findings of the International Nosocomial Infection Control Consortium. AB - BACKGROUND: Surgical site infections (SSIs) are the most common healthcare associated infections (HAI) in lower-income countries. This is the first study to report the results of surveillance on SSI stratified by surgical procedure in seven Vietnamese cities. METHODS: This was a prospective, active SSI surveillance study conducted from November 2008-December 2010 in seven hospitals using the U.S. Centers for Disease Control and Prevention's National Healthcare Safety Network (CDC-NHSN) definitions and methods. Surgical procedures (SPs) were classified into 26 types according to the International Classification of Diseases Edition 9 criteria. RESULTS: We recorded 241 SSIs, associated with 4,413 SPs (relative risk [RR] 5.5%; 95% confidence interval [95% CI] 4.8-6.2). The highest SSI rates were found for limb amputation (25%), colon surgery (33%), and small bowel surgery (21%). Compared with CDC-NHSN SSI report, our SSI rates were higher for the following SPs: Limb amputation (25% vs. 1.3%; RR 20.0; p = 0.001); appendix surgery (8.8% vs. 3.5%; RR 2.54; 95% CI 1.3-5.1; p = 0.001); gallbladder surgery (13.7% vs. 1.7%; RR 7.76; 95% CI 1.9-32.1; p = 0.001); colon surgery (18.2% vs. 4.0%; RR 4.56; 95% CI 2.0-10.2; p = 0.001); open reduction of fracture (15.8% vs. 3.4%; RR 4.70, 95% CI 1.5-15.2; p = 0.004); gastric surgery (7.3% vs. 1.7%; RR 4.26; 95% CI 2.2-8.4, p = 0.001); kidney surgery (8.9% vs. 0.9%; RR 10.2; 95% CI 3.8-27.4; p = 0.001); prostate surgery (5.1% vs. 0.9%; RR 5.71; 95% CI 1.9-17.4; p = 0.001); small bowel surgery (20.8% vs. 6.7%; RR 3.07; 95% CI 1.7 5.6; p = 0.001); thyroid or parathyroid surgery (2.4% vs. 0.3%; RR 9.27; 95% CI 1.0-89.1; p = 0.019); and vaginal hysterectomy (14.3% vs. 1.2%; RR 12.3; 95% CI 1.7-88.4; p = 0.001). CONCLUSIONS: Our SSIs rates were significantly higher for 11 of the 26 types of SPs than for the CDC-NHSN. This study advances our knowledge of SSI epidemiology in Vietnam and will allow us to introduce targeted interventions. PMID- 26885675 TI - Evaluating the Role of Cellular Immune Responses in the Emergence of HCV NS3 Resistance Mutations During Protease Inhibitor Therapy. AB - The efficacy of protease inhibitor drugs in hepatitis C virus (HCV) treatment is limited by the selection and expansion of drug-resistant mutations. HCV replication is error-prone and genetic variability within the dominant epitopes ensures its persistence. The aims of this study are to evaluate the role of cellular immune response in the emergence of HCV protease resistance mutations and its effects on treatment outcome. Ten chronically HCV-infected subjects were treated with boceprevir (BOC)-based triple therapy. HCV-RNA was tested for BOC resistance-associated viral variants. HCV protease resistance mutations were investigated pretreatment and 24 weeks post-treatment. Synthetic peptides representing the wild-type and the potential nonstructural (NS)3 variants were used to evaluate T cell responses and human leukocyte antigen binding. Sustained viral response was achieved in 70% of patients, two patients were treatment nonresponders (NRs) and one was classified as a relapse. Pretreatment, the proportion of drug-resistant variants within individuals was higher in sustained viral responders (SVRs) than in NR patients. However, resistance-associated variants increased in NRs after BOC combined triple therapy. In contrast to NR patients, significant stronger cell-mediated immune responses were observed at the baseline among those who achieved sustained viral response for all T cell epitopes tested. Despite the increase in cell-mediated immune responses at week 24 in NRs, they failed to control the virus replication, leading to development of overt drug-resistant variants. Our data suggest that strong NS3-specific T cell immune responses at the baseline may predict a positive outcome of directly acting antiviral-based therapy, and the presence of pre-existent resistance mutations does not play a significant role in the outcome of anti-HCV combined therapy. PMID- 26885678 TI - One-Pot and Facile Fabrication of Hierarchical Branched Pt-Cu Nanoparticles as Excellent Electrocatalysts for Direct Methanol Fuel Cells. AB - Hierarchical branched nanoparticles are one promising nanostructure with three dimensional open porous structure composed of integrated branches for superior catalysis. We have successfully synthesized Pt-Cu hierarchical branched nanoparticles (HBNDs) with small size of about 30 nm and composed of integrated ultrathin branches by using a modified polyol process with introduction of poly(vinylpyrrolidone) and HCl. This strategy is expected to be a general strategy to prepare various metallic nanostructures for catalysis. Because of the special open porous structure, the as-prepared Pt-Cu HBNDs exhibit greatly enhanced specific activity toward the methanol oxidation reaction as much as 2.5 and 1.7 times compared with that of the commercial Pt-Ru and Pt-Ru/C catalysts, respectively. Therefore, they are potentially applicable as electrocatalysts for direct methanol fuel cells. PMID- 26885679 TI - In vitro maturation alters gene expression in bovine oocytes. AB - Gene expression profiling of in vivo- and in vitro-matured bovine oocytes can identify transcripts related to the developmental potential of oocytes. Nonetheless, the effects of in vitro culturing oocytes are yet to be fully understood. We tested the effects of in vitro maturation on the transcript profile of oocytes collected from Bos taurus indicus cows. We quantified the expression of 1488 genes in in vivo- and in vitro-matured oocytes. Of these, 51 genes were up-regulated, whereas 56 were down-regulated (>=2-fold) in in vivo matured oocytes in comparison with in vitro-matured oocytes. Quantitative real time polymerase chain reaction (PCR) of nine genes confirmed the microarray results of differential expression between in vivo- and in vitro-matured oocytes (EZR, EPN1, PSEN2, FST, IGFBP3, RBBP4, STAT3, FDPS and IRS1). We interrogated the results for enrichment of Gene Ontology categories and overlap with protein protein interactions. The results revealed that the genes altered by in vitro maturation are mostly related to the regulation of oocyte metabolism. Additionally, analysis of protein-protein interactions uncovered two regulatory networks affected by the in vitro culture system. We propose that the differentially expressed genes are candidates for biomarkers of oocyte competence. In vitro oocyte maturation can affect the abundance of specific transcripts and are likely to deplete the developmental competence. PMID- 26885680 TI - Association of spinal degenerative disc disease with thyroid autoimmunity. AB - OBJECTIVES: Autoimmune thyroiditis (ATD) has been linked to various forms of arthritis. The relationship with spinal degenerative disc disease (DDD) is not known. We studied the association between ATD and spinal DDD. METHODS: We performed a cross-sectional analysis of patients who had data on both anti thyroid peroxidase antibodies (TPOAb) and anti-thyroglobulin antibodies (TgAb) from January 1997 to January 2014 in Clinical Looking Glass (CLG), a data analysis software platform. Spinal DDD was confirmed by radiological diagnosis. RESULTS: Of the 7698 patients for whom the TPOAb and TgAb values were available, 4383 patients with complete data for the following covariates; age, gender, race, ethnicity, smoking, diabetes, body mass index and thyroid stimulating hormone (TSH) levels, were included. Thirty-three percent had ATD, while 67% did not. The unadjusted odds ratio (OR) of having spinal DDD with ATD was 1.5 (95% confidence interval (CI)1.3, 1.7), p<0.001. After adjustment for covariates, ATD remained associated with a higher frequency of spinal DDD, OR 1.8 (95% CI 1.6, 2.2), p<0.001. Stratifying by BMI and TSH levels showed similar results. Additional analyses excluding patients with known connective tissue diseases and spondyloarthritis (SpA) also showed consistent results. CONCLUSIONS: ATD is associated with increased frequency of spinal DDD independent of BMI and TSH levels, and among those without connective tissue diseases or SpA. This finding suggests that there may be an important link between thyroid autoimmunity and spinal DDD. PMID- 26885681 TI - Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma. AB - Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age +/- standard deviation, 52.4 years +/- 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years +/- 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may prolong overall survival when compared with TACE alone. ((c)) RSNA, 2016. PMID- 26885682 TI - Stiffness Value and Serum Biomarkers in Liver Fibrosis Staging: Study in Large Surgical Specimens in Patients with Chronic Hepatitis B. AB - Purpose To investigate the capabilities of stiffness value and serum biomarkers in the staging of liver fibrosis in patients with chronic hepatitis B (CHB), with pathologic findings in large surgical specimens serving as the reference standard. Materials and Methods This study was approved by the institutional review board, and informed consent was obtained from all patients. Liver stiffness (determined by means of ultrasonography-based elastography point quantification), aspartate aminotransferase-platelet ratio index (APRI), and fibrosis index (based on the four-factor Fibrosis-4 [FIB-4] calculation) were obtained in 386 patients with CHB. With pathologic fibrosis stages in large surgical specimens as the reference standard, capabilities and cutoffs of stiffness and serum biomarkers were first investigated in a cohort of 284 patients and then validated in an independent cohort of 102 patients by means of area under the receiver operating characteristic curve (AUC) analysis. Results Liver stiffness demonstrated significantly stronger correlation with fibrosis stages than did APRI and FIB-4 (r = 0.738 vs r = 0.477 vs r = 0.427, respectively; P < .05 for all). In the development cohort, liver stiffness had significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.97, 0.96, 0.91, and 0.87, respectively) than APRI (0.89, 0.84, 0.73, and 0.74, respectively) and FIB-4 (0.82, 0.79, 0.70, and 0.72, respectively). In the validation cohort, liver stiffness was validated as showing significantly higher AUCs in identifying fibrosis of stage 1 or higher, stage 2 or higher, stage 3 or higher, and stage 4 or higher (0.99, 0.95, 0.89, and 0.88, respectively) than APRI (0.83, 0.76, 0.78, and 0.68, respectively) and FIB-4 (0.76, 0.69, 0.75, and 0.67, respectively). Conclusion Liver stiffness demonstrated considerable capability in identifying each stage of liver fibrosis in patients with CHB, whereas serum biomarkers showed limited capabilities. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26885683 TI - Is the Adolescent and Young Adult Cancer Survivor at Risk for Late Effects? It Depends on Where You Look. AB - PURPOSE: The adolescent and young adult (AYA) population is a growing group of survivors, exceeding more than 600,000, at high risk for late effects of cancer directed therapy. While many guidelines exist for cancer survivorship care, choosing which to use for an AYA cancer survivor is challenging, yet vital, to ensure comprehensive follow-up care. METHODS: Survivorship care plans (SCPs), including treatment summaries (TS) and follow-up care plans, were created for three clinical vignettes (acute lymphoblastic leukemia, osteosarcoma, and Hodgkin lymphoma). Four sets of guidelines were used, including the Children's Oncology Group Long-Term Follow-Up Guidelines (COG LTFU), National Comprehensive Cancer Network (NCCN) Guidelines for Age- Related Recommendations: AYA Oncology (NCCN AYA), NCCN Guidelines for Treatment of Cancer by Site (NCCN-Site), and NCCN Guidelines for Supportive Care: Survivorship (NCCN-Survivorship) and NCCN supplemental cancer screening guidelines. The follow-up care plans were compared across guidelines to determine the extent and nature of the similarities and differences concerning AYA cancer survivorship care. RESULTS: The guidelines disagree on the link between treatment exposures and late effects, the population to be screened, the screening test to be used, and the time interval of testing. Specific examples of this include screening for cardiac toxicity, breast cancer, and neurocognitive deficits. CONCLUSIONS: While many guidelines exist for AYA survivorship care, there is discordance among the recommendations. This has significant implications for the long-term follow-up care of an AYA survivor. This study offers solutions to harmonize guidelines in order to ensure comprehensive quality survivorship care for this population. PMID- 26885684 TI - Gallium as a Therapeutic Agent: A Thermodynamic Evaluation of the Competition between Ga(3+) and Fe(3+) Ions in Metalloproteins. AB - Gallium has been employed (in the form of soluble salts) to fight various forms of cancer, infectious, and inflammatory diseases. The rationale behind this lies in the ability of Ga(3+) cation to mimic closely in appearance the native ferric ion, Fe(3+), thus interfering with the biological processes requiring ferric cofactors. However, Ga(3+) ion cannot participate in redox reactions and, when substituting for the "native" Fe(3+) ion in the enzyme active site, renders it inactive. Although a significant body of information on the Ga(3+)-Fe(3+) competition in biological systems has been accumulated, the intimate mechanism of the process is still not well understood and several questions remain: What are the basic physical principles governing the competition between the two trivalent cations in proteins? What type of metal centers are the most likely targets for gallium therapy? To what extent are the Fe(3+)-binding sites in the key enzyme ribonucleotide reductase vulnerable to Ga(3+) substitution? Here, we address these questions by studying the competition between Ga(3+) and Fe(3+) ions in model metal binding sites of various compositions and charge states. The results obtained are in line with available experimental data and shed light on the intimate mechanism of the Ga(3+)/Fe(3+) selectivity in various model metal binding sites and biological systems such as serum transferrin and ribonucleotide reductase. PMID- 26885685 TI - Medical record keeping and system performance in orthopaedic trauma patients. AB - Objective The medical record is critical for documentation and communication between healthcare professionals. The aim of the present study was to evaluate important aspects of the orthopaedic medical record and system performance to determine whether any deficiencies exist in these areas. Methods Review of 200 medical records of surgically treated traumatic lower limb injury patients was undertaken. The operative report, discharge summary and first and second outpatient reviews were evaluated. Results In all cases, an operative report was completed by a senior surgeon. Weight-bearing status was adequately documented in 91% of reports. Discharge summaries were completed for 82.5% of admissions, with 87.3% of these having instructions reflective of those in the operative report. Of first and second outpatient reviews, 69% and 73%, respectively, occurred within 1 week of the requested time. Previously documented management plans were changed in 30% of reviews. At 6-months post-operatively, 42% of patients had been reviewed by a member of their operating team. Discussion Orthopaedic medical record documentation remains an area for improvement. In addition, hospital out patient systems perform suboptimally and may affect patient outcomes. What is known about the topic? Medical records are an essential tool in modern medical practice. Despite the importance of comprehensive documentation in the medical record, numerous examples of poor documentation have been demonstrated, including substandard documentation during consultant ward rounds by junior doctors leading to a breakdown in healthcare professional communication and potential patient mismanagement. Further inadequacies of medical record documentation have been demonstrated in surgical discharge notes, with complete and correct documentation reported to be as low as 65%. What does this paper add? Standards of patient care should be constantly monitored and deficiencies identified in order to implement a remedy and close the quality loop. The present study has highlighted that the standard of orthopaedic trauma medical record keeping at an Australian Level 1 trauma centre is below what is expected and several key areas of documentation require improvement. This paper further evaluates the system performance of the out-patient system, an area where, to the authors knowledge, there is no previous work published. The findings show that the performance was below what is expected for surgical review, with many patients failing to be reviewed by their operating surgeon. What are the implications for practitioners? The present study shows that there is a poor level of documentation and a standard of out-patient review below what is expected. The implications of these findings will be to highlight current deficiencies to practitioners and promote change in current practice to improve the quality of medical record documentation among medical staff. Further, the findings of poor system performance will promote change in the current system of delivering out-patient care to patients. PMID- 26885687 TI - Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder. AB - The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave induced mTBI and PTSD and comorbid mTBI-PTSD. PMID- 26885686 TI - The efficacy and safety of a new reduced-toxicity conditioning with 4 days of once-daily 100 mg/m(2) intravenous busulfan associated with fludarabine and antithymocyte globulins prior to allogeneic stem cell transplantation in patients with high-risk myelodysplastic syndrome or acute leukemia. AB - The optimal intensity of myeloablation associated with a reduced-toxicity conditioning (RTC) regimen in order to decrease the relapse rate without increasing non-relapse mortality (NRM), is not well established yet. This retrospective analysis was done on 30 patients with hematological malignancies. The aim was to assess the safety of a RTC regimen based on the busulfan at a dose of 100 mg/m(2)/d intravenously for 4 d, fludarabine at a dose of 30 mg/m(2)/d for 5 d, and anti-thymoglobulins at a dose of 2.5 mg/kg/d for 2 d. The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and all grades chronic GVHD were 37% and 42%, respectively. Median 1-year overall survival and disease-free survival were 66% and 50%, respectively. At 1 year, the cumulative incidence of relapse/disease progression was 33%. NRM was 3% and 17% at day 100 and 1 year, respectively. This RTC conditioning regimen can lead to a long-term disease control. Moreover, it appears to be safe with a low NRM rate among high risk patients. PMID- 26885688 TI - Comparative effectiveness of light emitting diodes (LEDs) and Lasers in near infrared photoimmunotherapy. AB - Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein we compare two NIR-light sources; light emitting diodes (LEDs) and Lasers, for their effectiveness in NIR-PIT. A photosensitizer, IRDye-700DX, conjugated to panitumumab (pan-IR700), was incubated with EGFR-expressing A431 and MDA-MB-468 luc cells. NIR-light was provided by LEDs or Lasers at the same light dose. Laser light produced more cytotoxicity and greater reductions in IR700-fluorescence intensity than LED-light. Laser-light also produced more cytotoxicity in vivo in both cell lines. Assessment of super-enhanced permeability and retention (SUPR) effects were stronger with Laser than LED. These results suggest that Laser-light produced significantly more cytotoxic effects compared to LEDs. Although LED is less expensive, Laser-light produces superior results in NIR-PIT. PMID- 26885689 TI - mir-329 restricts tumor growth by targeting grb2 in pancreatic cancer. AB - Pancreatic cancer is one of the most lethal malignancies worldwide. To illustrate the pathogenic mechanism(s), we looked into the expression and function of miR 329 associated with pancreatic cancer development. It was found that miR-329 expression was downregulated in the pancreatic cancer patients who demonstrated significantly shorter overall survival than the patients having upregulated expression. Also, more advanced pT stage cases were observed in the low miR-329 expression group of patients. Interestingly, our studies uncovered that miR-329 overexpression inhibited proliferation and induced apoptosis of pancreatic cancer cells, in contrast the miR-329 inhibitor reversed this phenomenon dramatically. Additionally, overexpression of miR-329 significantly limited tumor growth in the xenograft model. In the mechanistic study, we identified GRB2 as a direct target of miR-329 in pancreatic cancer cells, and expression of GRB2 was inversely correlated with miR-329 expression in pancreatic cancer patients. Furthermore, GRB2 overexpression in cell line and xenograft model dramatically diminished miR 329 mediated anti-proliferation and apoptosis induction, indicating that GRB2/pERK pathway was mainly downregulated by miR-329 expression. In general, our study has shed light on miR-329 regulated mechanism and, miR-329/GRB2/pERK is potential to be targeted for pancreatic cancer management. PMID- 26885690 TI - Targeting the CCL2-CCR2 signaling axis in cancer metastasis. AB - The CCL2-CCR2 signaling axis has generated increasing interest in recent years due to its association with the progression of cancer. Although first described as a chemotactic molecule with physiological roles in regulating inflammation, recent studies have revealed a pro-tumorigenic function for CCL2 in favoring cancer development and subsequent metastasis. CCL2 binds the cognate receptor CCR2, and together this signaling pair has been shown to have multiple pro tumorigenic roles, from mediating tumor growth and angiogenesis to recruiting and usurping host stromal cells to support tumor progression. The importance of CCL2 CCR2 signaling has been further championed by the establishment of clinical trials targeting this signaling pair in solid and metastatic cancers. Here we review the roles of CCL2-CCR2 signaling in the development and progression of cancer metastasis. We further evaluate the outcome of several clinical trials targeting either CCL2 or CCR2, and discuss the prospects and challenges of manipulating CCL2-CCR2 interaction as a potential approach for combating metastatic disease. PMID- 26885692 TI - Cervical cancer systemic inflammation score: a novel predictor of prognosis. AB - Inflammation contributes to development and progression in a variety of cancers, including cervical cancer. We developed a novel cervical cancer systemic inflammation score (CCSIS) based on the preoperative platelet-to-lymphocyte ratio (PLR) and serum albumin levels. A retrospective analysis of clinical data from 795 patients with operable cervical cancer was then conducted to investigate the prognostic value of CCSIS and its association with the patients' clinicopathological features, overall survival (OS), and disease-free survival (DFS). CCSIS was predictive of OS and DFS. High CCSIS was correlated with more advanced FIGO stages, poor tumor differentiation, and the presence of PLN and LVSI. Both albumin levels and the PLR were independent prognostic indicators for operable cervical cancer. The use of the CCSIS could improve risk stratification and traditional clinicopathological analysis in cervical cancer. PMID- 26885693 TI - Teaching dementia care to physical therapy doctoral students: A multimodal experiential learning approach. AB - As the population aged 65 and older grows, it becomes imperative for health care providers to expand their knowledge regarding geriatric conditions and concerns. Dementia is a devastating degenerative disease process that is affecting millions of individuals in the United States, with significant economic and emotional burden on family and caregivers. The need for further dementia education in physical therapy school is essential to improve attitudes and treatment that affect patient outcomes and quality of care. This physical therapy program implemented a 12-hour multimodal experiential learning module designed to educate their students on the challenges associated with dementia to increase knowledge and confidence when treating these patients. The results of this study showed statistically significant improvements in overall confidence and knowledge of treating patients with dementia. The study finds the addition of experiential learning to traditional didactic coursework improves students' reported confidence in working with patients with dementia and understanding the challenges associated with treating patients with dementia. PMID- 26885691 TI - The RNA helicase A in malignant transformation. AB - The RNA helicase A (RHA) is involved in several steps of RNA metabolism, such as RNA processing, cellular transit of viral molecules, ribosome assembly, regulation of transcription and translation of specific mRNAs. RHA is a multifunctional protein whose roles depend on the specific interaction with different molecular partners, which have been extensively characterized in physiological situations. More recently, the functional implication of RHA in human cancer has emerged. Interestingly, RHA was shown to cooperate with both tumor suppressors and oncoproteins in different tumours, indicating that its specific role in cancer is strongly influenced by the cellular context. For instance, silencing of RHA and/or disruption of its interaction with the oncoprotein EWS-FLI1 rendered Ewing sarcoma cells more sensitive to genotoxic stresses and affected tumor growth and maintenance, suggesting possible therapeutic implications. Herein, we review the recent advances in the cellular functions of RHA and discuss its implication in oncogenesis, providing a perspective for future studies and potential translational opportunities in human cancer. PMID- 26885696 TI - The buffering effect of family functioning on the psychological consequences of headache. AB - The current study aimed to examine whether high family functioning mitigates the association between headache intensity and distress. The sample consisted of 124 patients with chronic or recurrent headache. Patients completed validated questionnaires about headache intensity, family functioning, and distress. Hierarchical regression analyses were performed to examine the interaction between headache intensity and family functioning on distress. Headache intensity was positively associated with distress (r = .28, p = .002). As hypothesized, family functioning moderated this association (B = -.01, p = .023). More specifically, the positive association between headache intensity and distress was significant only among patients with lower family functioning (B = .01, p < .001) and not among patients with higher levels of family functioning (B = .006, p = .075). Functional families appear to buffer the distress level in patients; they showed relatively low levels of distress regardless of the severity of their headache. In contrast, patients with dysfunctional families who experienced more pain reported more distress, presumably because they did not receive adequate help and support from these families. This study underlines the importance of a broader perspective on family dynamics in coping with pain. PMID- 26885695 TI - Phenotypic observations in "hypotrichosis with juvenile macular dystrophy" (recessive CDH3 mutations). AB - PURPOSE: Recessive mutations in CDH3 cause "hypotrichosis with juvenile macular dystrophy," typically recognized by the presence of prominent dermatological features. We report novel phenotypic observations and associated mutations in four patients from three families, including one who did not have frank hypotrichosis. METHODS: Retrospective case series (2010-2014). RESULTS: Four affected individuals from three consanguineous Arabian families were identified. All four subjects (two sisters and two unrelated males; 5, 13, 17, and 26 years old) had homozygous recessive CDH3 mutations not previously associated with the condition (c.307C>T; p.R103 in two sisters, c.1859_1862delCTCT in both unrelated males). Symptomatic visual loss was since birth or early childhood. One male subject did not have frank hypotrichosis, but review of symptoms revealed relatively slow hair growth and an inability to conceive children. None had dental or digital findings, although one female noted slow nail growth. All had a circumscribed central maculopathy with borders that did not respect posterior pole horizontal arterioles (typically extending beyond the major arcades) and associated with polygonal pigment clumping. Recognition of this pattern led us to suspect the diagnosis in the male without frank hypotrichosis. Retinal dysfunction was cone-rod (rather than macular only) by ERG in one patient, who developed severe central macular atrophy and a macular hole. CONCLUSIONS: Ophthalmologists should consider the diagnosis of CDH3-related retinopathy in individuals with such clinical features whether or not there is frank hypotrichosis. PMID- 26885697 TI - A 7-Year Longitudinal Trial of the Safety and Efficacy of a Vitamin/Mineral Enhanced Plant-Sourced Calcium Supplement. AB - OBJECTIVES: The objective of this study was to examine the safety and efficacy of a vitamin-mineral enhanced plant-sourced calcium AlgaeCal calcium (AC) in female consumers who had taken the supplement from 1 to 7 years. METHODS: Consumers who had completed at least one dual-energy x-ray absorptiometry (DEXA) bone mineral density (BMD) scan (N = 172) and/or blood chemistry test (N = 30) and purchased AC from 1 to 7 years were contacted and offered complimentary repeat tests. Safety and efficacy were examined by annualized changes in a 45-measurement blood chemistry panel and changes in BMD. RESULTS: No adverse effects or safety concerns were found in any of the annualized within-group annualized changes in the 45 blood chemistries or in between-group changes in a similar control group (n = 5070) who completed the same measurements. With regard to BMD, consistent and statistically significant within-group increases were found for the 7-year study period and when compared to expected BMD changes in 3 large databases or the combination (N = 25,885) of the 3 databases. Data from this study suggest that AC supplement was associated with a significant annualized and linear increase in BMD of 1.04% per year, 7.3% over the 7-year study period. These results stand in marked contrast to normative or expected changes of -0.4%/y from 3 different databases or in a combination of all 3 databases (N = 16,289). CONCLUSIONS: No evidence was found in cardiovascular risk as measured by adverse changes in blood lipids, nor was any evidence found of a diminished efficacy over the 7-year study period because gains in BMD were consistent and linear over the 7-year study period, averaging 1.04% per year over the 7-year study. The results are also consistent with earlier short-term studies suggesting that this supplement can facilitate significant increases in total body BMD in contrast to studies suggesting that calcium supplements can only slow down age-related declines in BMD. PMID- 26885694 TI - Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIbeta. AB - Type III phosphatidylinositol 4-kinase (PI4KIIIbeta) is an essential enzyme in mediating membrane trafficking and is implicated in a variety of pathogenic processes. It is a key host factor mediating replication of RNA viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. We previously reported the PI4K inhibitor PIK93, and this compound has defined key functions of PI4KIIIbeta. However, this compound showed high cross reactivity with class I and III PI3Ks. Using structure-based drug design, we have designed novel potent and selective (>1000-fold over class I and class III PI3Ks) PI4KIIIbeta inhibitors. These compounds showed antiviral activity against hepatitis C virus. The co-crystal structure of PI4KIIIbeta bound to one of the most potent compounds reveals the molecular basis of specificity. This work will be vital in the design of novel PI4KIIIbeta inhibitors, which may play significant roles as antiviral therapeutics. PMID- 26885698 TI - In Situ Electrochemical Generation of Electrochemiluminescent Silver Naonoclusters on Target-Cycling Synchronized Rolling Circle Amplification Platform for MicroRNA Detection. AB - On the basis of a novel target-cycling synchronized rolling circle amplification (RCA) as a signal amplification strategy and in situ electrochemical generation of silver nanoclusters (Ag NCs) as signal probes, an ultrasensitive and simple electrochemiluminescence (ECL) biosensor was proposed for microRNA (miRNA) detection. It was worth mentioning that the circular template was subtly designed to consist of a guanine-rich (G-rich) region and a binding region for realizing target-cycling synchronized RCA. In the presence of target miR-21, the binding region hybridized with the primer and the target miR-21 to form a ternary "P" junction structure, and then the RCA was triggered from the 3'-end of the primer. Along with the proceeding of RCA, the target miR-21 was released and participated into another trigger of the RCA. On account of the G-rich region in the circular template, the product DNA of the target-cycling synchronized RCA possessed tandem periodic cytosine-rich (C-rich) sequences, which acted as ligands to further in situ electrochemically generate silver nanoclusters (Ag NCs) as ECL signal probes. As expected, the obtained ECL intensity dependent on the amount of the Ag NCs, which was positively related to the concentration of the target miR-21. The ECL assay for miR-21 detection demonstrated excellent linear response to a concentration variation from 100 aM to 100 pM and limit of detection down to 22 aM. PMID- 26885699 TI - Life-Span Development of Brain Network Integration Assessed with Phase Lag Index Connectivity and Minimum Spanning Tree Graphs. AB - Graph analysis of electroencephalography (EEG) has previously revealed developmental increases in connectivity between distant brain areas and a decrease in randomness and increased integration in the brain network with concurrent increased modularity. Comparisons of graph parameters across age groups, however, may be confounded with network degree distributions. In this study, we analyzed graph parameters from minimum spanning tree (MST) graphs and compared their developmental trajectories to those of graph parameters based on full graphs published previously. MST graphs are constructed by selecting only the strongest available connections avoiding loops, resulting in a backbone graph that is thought to reflect the major qualitative properties of the network, while allowing a better comparison across age groups by avoiding the degree of distribution confound. EEG was recorded in a large (n = 1500) population-based sample aged 5-71 years. Connectivity was assessed using phase lag index to reduce effects of volume conduction. Connectivity in the MST graph increased significantly from childhood to adolescence, continuing to grow nonsignificantly into adulthood, and decreasing significantly about 57 years of age. Leaf number, degree, degree correlation, and maximum centrality from the MST graph indicated a pattern of increased integration and decreased randomness from childhood into early adulthood. The observed development in network topology suggested that maturation at the neuronal level is aimed to increase connectivity as well as increase integration of the brain network. We confirm that brain network connectivity shows quantitative changes across the life span and additionally demonstrate parallel qualitative changes in the connectivity pattern. PMID- 26885700 TI - Ligand-Induced Formation of Copper(I) Iodide Clusters: Exocyclic Coordination Polymers with Bis-dithiamacrocycle Isomers. AB - A comparative study on the formation of guest clusters induced by different shapes (or sizes) of exocyclic binding sites embedded in the bis-macrocyclic host isomers is reported. CuI reacts with two regioisomers of a bis-dithiamacrocycle, o-bis-L (W-shaped binding site) and m-bis-L (U-shaped binding site), to yield one dimensional coordination polymers {[(MU4-Cu4I4)(o-bis-L)].2CH3CN}n (1a) and [(MU4 Cu2I2)(m-bis-L)]n (2). In 1a, the o-bis-L ligand isomer is linked by a spacious cubane [Cu4I4] cluster, while the m-bis-L ligand in 2 is linked by a smaller rhomboid [Cu2I2] cluster because of the different exocyclic binding sites. The results observed illustrate the possibility for the metal clusters including [CunIn] (n = 2 or 4) to adopt a controlled formation through the binding site alternation or design. Because of the adaptive cluster formations, the products show different photophysical properties. Additionally, sliding of the one dimensional chains in 1a was observed upon loss of the lattice solvent molecules in ambient condition. PMID- 26885701 TI - Imaging Nanostructures by Single-Molecule Localization Microscopy in Organic Solvents. AB - The introduction of super-resolution fluorescence microscopy (SRM) opened an unprecedented vista into nanoscopic length scales, unveiling a new degree of complexity in biological systems in aqueous environments. Regrettably, supramolecular chemistry and material science benefited far less from these recent developments. Here we expand the scope of SRM to photoactivated localization microscopy (PALM) imaging of synthetic nanostructures that are highly dynamic in organic solvents. Furthermore, we characterize the photophysical properties of commonly used photoactivatable dyes in a wide range of solvents, which is made possible by the addition of a tiny amount of an alcohol. As proof-of-principle, we use PALM to image silica beads with radii close to Abbe's diffraction limit. Individual nanoparticles are readily identified and reliably sized in multicolor mixtures of large and small beads. We further use SRM to visualize nm-thin yet MUm-long dynamic, supramolecular polymers, which are among the most challenging molecular systems to image. PMID- 26885703 TI - Localized NMR Mediated by Electrical-Field-Induced Domain Wall Oscillation in Quantum-Hall-Ferromagnet Nanowire. AB - We present fractional quantum Hall domain walls confined in a gate-defined wire structure. Our experiments utilize spatial oscillation of domain walls driven by radio frequency electric fields to cause nuclear magnetic resonance. The resulting spectra are discussed in terms of both large quadrupole fields created around the wire and hyperfine fields associated with the oscillating domain walls. This provides the experimental fact that the domain walls survive near the confined geometry despite of potential deformation, by which a localized magnetic resonance is allowed in electrical means. PMID- 26885702 TI - High Baseline Postconcussion Symptom Scores and Concussion Outcomes in Athletes. AB - CONTEXT: Some healthy athletes report high levels of baseline concussion symptoms, which may be attributable to several factors (eg, illness, personality, somaticizing). However, the role of baseline symptoms in outcomes after sport related concussion (SRC) has not been empirically examined. OBJECTIVE: To determine if athletes with high symptom scores at baseline performed worse than athletes without baseline symptoms on neurocognitive testing after SRC. DESIGN: Cohort study. SETTING: High school and collegiate athletic programs. PATIENTS OR OTHER PARTICIPANTS: A total of 670 high school and collegiate athletes participated in the study. Participants were divided into groups with either no baseline symptoms (Postconcussion Symptom Scale [PCSS] score = 0, n = 247) or a high level of baseline symptoms (PCSS score > 18 [top 10% of sample], n = 68). MAIN OUTCOME MEASURE(S): Participants were evaluated at baseline and 2 to 7 days after SRC with the Immediate Post-concussion Assessment and Cognitive Test and PCSS. Outcome measures were Immediate Post-concussion Assessment and Cognitive Test composite scores (verbal memory, visual memory, visual motor processing speed, and reaction time) and total symptom score on the PCSS. The groups were compared using repeated-measures analyses of variance with Bonferroni correction to assess interactions between group and time for symptoms and neurocognitive impairment. RESULTS: The no-symptoms group represented 38% of the original sample, whereas the high-symptoms group represented 11% of the sample. The high symptoms group experienced a larger decline from preinjury to postinjury than the no-symptoms group in verbal (P = .03) and visual memory (P = .05). However, total concussion-symptom scores increased from preinjury to postinjury for the no symptoms group (P = .001) but remained stable for the high-symptoms group. CONCLUSIONS: Reported baseline symptoms may help identify athletes at risk for worse outcomes after SRC. Clinicians should examine baseline symptom levels to better identify patients for earlier referral and treatment for their injury. Additional investigation of baseline symptoms is warranted to help delineate the type and severity of premorbid symptoms. PMID- 26885704 TI - Polarization of ferroelectric films through electrolyte. AB - A simplified model is developed to understand the field and potential distribution through devices based on a ferroelectric film in direct contact with an electrolyte. Devices based on the ferroelectric polymer polyvinylidenefluoride trifluoroethylene (PVDF-TrFE) were produced--in metal-ferroelectric-metal, metal ferroelectric-dielectric-metal, and metal-ferroelectric-electrolyte-metal architectures--and used to test the model, and simulations based on the model and these fabricated devices were performed. From these simulations we find indication of progressive polarization of the films. Furthermore, the model implies that there is a relation between the separation of charge within the devices and the observed open circuit voltage. This relation is confirmed experimentally. The ability to polarize ferroelectric polymer films through aqueous electrolytes, combined with the strong correlation between the properties of the electrolyte double layer and the device potential, opens the door to a variety of new applications for ferroelectric technologies, e.g. regulation of cell culture growth and release, steering molecular self-assembly, or other large area applications requiring aqueous environments. PMID- 26885705 TI - The main progress over the past decade and future outlook on high-nuclear transition-metal substituted polyoxotungstates: from synthetic strategies, structural features to functional properties. AB - Currently, transition-metal substituted polyoxotungstates (TMSPTs) have developed as a fast growing and challengeable subfamily of polyoxoxmetalates (POMs). Before 2005, the number of TM cores in TMSPTs was mostly lower than five. Since 2005, numerous inorganic or organic-inorganic TMSPTs with more than five TM cores (denoted as high-nuclear TMSPTs) have continuously been excavated and investigated. In this perspective, we endeavor to discuss the synthetic methodologies, structural diversities and relevant properties of the high-nuclear TMSPTs reported in the past decade. Future perspectives and opportunities on TMSPTs are included in the last section. This review is meant to provide fodder and guidance for further exploration and discovery of more high-nuclear TMSPTs with innovative architectures and remarkable functionality. PMID- 26885706 TI - Laboratory animal allergy: a new world. AB - PURPOSE OF REVIEW: In recent years there has been a dramatic shift in the world of animal research whereby genetically modified mice have largely supplanted rats, and individually ventilated cages have been introduced to house delicate experimental animals in place of traditional open cages. Although laboratory animal allergy remains an important cause of occupational asthma, the risks associated with contemporary practice and consequently the opportunities for primary and secondary prevention are largely unknown. RECENT FINDINGS: Although there is clear confirmation of a widespread increase in animal experiments using mice, the evidence-base on the associated risks has lagged. Individually ventilated cages reduce ambient levels of mouse urinary protein in air but task based exposures are unquantified. Immunological techniques to identify sensitization to mouse proteins are poorly standardized. The available evidence suggests that modern practices are, in most cases, associated with a reduced incidence of animal sensitization. SUMMARY: There is a paucity of data to inform evidence-based practice in methods to control the incidence of laboratory animal allergy under the prevailing research environment; a better understanding of the relationship between exposures and outcome is urgently needed. As exposures decline, the relative importance of individual susceptibility will become prominent. PMID- 26885708 TI - Left Ventricular Dysfunction After Treatment With Ipilimumab for Metastatic Melanoma. AB - Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) that is approved by the US Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Ipilimumab is known to cause immune-mediated adverse reactions because of the resultant increase in T cell activity. To date, there are no published reports of ipilimumab-related heart failure, although a recently published report describes a case of transient cardiomyopathy associated with its use. We report the case of a 60-year-old man who developed left ventricular dysfunction with an asymptomatic reduction in ejection fraction from 55%-60% at baseline to 40%-45% 4 months after completing a second course of treatment with ipilimumab for metastatic melanoma. Ipilimumab was not restarted, and the patient was initiated on lisinopril and carvedilol. Repeat echocardiograms 3 and 5 months later revealed ejection fractions of 40% 45% and 55%-60%, respectively. PMID- 26885710 TI - Manganism and Parkinson's disease: Mn(II) and Zn(II) interaction with a 30-amino acid fragment. AB - A protected 30-amino acid fragment, Acetyl-SPDEKHELMIQLQKLDYTVGFCGDGANDCG-Amide, Acetyl-Ser-Pro-Asp-Glu-Lys-His-Glu-Leu-Met-Ile-Gln-Leu-Gln-Lys-Leu-Asp-Tyr-Thr Val-Gly-Phe-Cys-Gly-Asp-Gly-Ala-Asn-Asp-Cys-Gly-Amide, encompassing the sequence from residues 1164 to 1193 in the encoded protein from Parkinson's disease gene Park9 (YPk9), was studied for manganese and zinc binding. Manganese exposure is considered to be an environmental risk factor connected to PD and PD-like syndrome. Research into the genetic and environmental risk factors involved in disease susceptibility has recently uncovered a link existing between Park9 and manganese. It seems that manganese binding to Park9 (YPk9) protein is involved in the detoxification mechanism exerted by this protein against manganese toxicity. In this study, we used potentiometric, mono- and bi-dimensional (TOCSY, HSQC) NMR, EPR and ESI-MS measurements to analyze complex formation and metal binding sites in the peptide fragment. Presumably octahedral species, in which the Mn(II) ion was bound to oxygens of the carboxyl groups of Glu and Asp, and species where the involvement of sulfur from Cys and nitrogen from His residues, depending on the metal to ligand molar ratio, were detected for manganese coordination. Structural changes in the 30-amino acid fragment were triggered by Zn(II) interaction. A general decrease in the intensity of NMR signals was detected, suggesting the occurrence of chemical exchange among some coordinated species in an intermediate NMR timescale. The coordination may involve both S and N donor atoms from cysteine as well as histidine residues, together with O donor atoms from glutamic and aspartic residues. PMID- 26885711 TI - Asymmetric Papilledema in Idiopathic Intracranial Hypertension: Comment. PMID- 26885712 TI - Orthopaedic Surgeon Burnout: Diagnosis, Treatment, and Prevention. AB - Burnout is a syndrome marked by emotional exhaustion, depersonalization, and low job satisfaction. Rates of burnout in orthopaedic surgeons are higher than those in the general population and many other medical subspecialties. Half of all orthopaedic surgeons show symptoms of burnout, with the highest rates reported in residents and orthopaedic department chairpersons. This syndrome is associated with poor outcomes for surgeons, institutions, and patients. Validated instruments exist to objectively diagnose burnout, although family members and colleagues should be aware of early warning signs and risk factors, such as irritability, withdrawal, and failing relationships at work and home. Emerging evidence indicates that mindfulness-based interventions or educational programs combined with meditation may be effective treatment options. Orthopaedic residency programs, departments, and practices should focus on identifying the signs of burnout and implementing prevention and treatment programs that have been shown to mitigate symptoms. PMID- 26885707 TI - The microbiome and development of allergic disease. AB - PURPOSE OF REVIEW: First, to review how the global rise in prevalence of asthma prompted studies of the relationships between microbial exposure in early infancy, the rate and pattern of development of immune function, and the development of allergic sensitization and of wheezing in childhood. And, second, to review how those studies laid the groundwork for a possible strategy for primary prevention of asthma through manipulation of the microbiome of the gastrointestinal and/or respiratory tracts. RECENT FINDINGS: Atopy and asthma are complex diseases thought to result from a 'gene-by-environment' interaction; the rapidity of their rise in prevalence points to a change in environment as most likely causal. Epidemiologic studies noting associations between events in infancy and later development of atopic diseases have suggested that their rise in prevalence is related to a deficiency in microbial exposure in early life. The findings from birth cohort studies of humans and from interventional studies of mice converge in suggesting that a deficiency in microbial colonization of the respiratory or gastrointestinal tract by certain commensal microbes results in skewed development of systemic and/or local immune function that increases susceptibility to allergic sensitization and to viral lower respiratory infection. Recent studies are now honing in on identifying the microbes, or collection of microbes, whose collective functions are necessary for induction of immune tolerance, and thus of reduced susceptibility. SUMMARY: Atopy and asthma appear to have their roots in an insufficiency of early-life exposure to the diverse environmental microbiota necessary to ensure colonization of the gastrointestinal and/or respiratory tracts with the commensal microbes necessary for induction of balanced, toleragenic immune function. Identification of the commensal bacteria necessary, now ever closer at hand, will lay the groundwork for the development of strategies for primary prevention of atopic disease, especially of childhood asthma. PMID- 26885713 TI - Norepinephrine, the Intensivist's Swiss Army Knife for Circulatory Shock? PMID- 26885715 TI - Near-Full-Length Genome Sequences of a Novel HIV-1 Circulating Recombinant Form, CRF01_AE/B'/C (CRF78_cpx), in Yunnan, China. AB - We report a novel HIV circulating recombinant form (CRF78_cpx) composed mainly of CRF01_AE with inserts from subtypes B and C identified from three epidemiologically unlinked individuals in Yunnan province, China. Two of the subjects are heterosexual men and one is a male intravenous drug user. Sequencing and analyzing the near-full-length genome of these three isolates (YNTC88, YNTC19, and YNTC35) revealed identical recombination breakpoints in all three viruses, but considerable genetic diversity between them, across the genomes, indicating that this is not a newly created CRF, only newly detected. CRF78_cpx differs from previously documented CRF01-AE/B'/C forms in its distinct backbone, inserted fragment size, and breakpoints, and is not related to other described recombinants in the region such as CRF07_BC or CRF65_cpx (also composed of CRF01_AE, B', and C). Our present findings further enrich the diversity of the prevalent HIV-1 CRFs in Yunnan, which is considered as an epicenter of HIV-1 infections in China. PMID- 26885714 TI - Comparison of black, green and rooibos tea on osteoblast activity. AB - Globally, tea is the second most consumed beverage after water. Habitual tea intake has been associated with higher bone mineral density, particularly in postmenopausal women. This association may be due to its polyphenols and resulting protective antioxidant effects. While in vivo studies have shown improved bone outcomes with a consumption of individual purified tea polyphenols, it is unclear if a particular tea - due to its different profiles of polyphenols is more beneficial than others. Therefore, we compared three different types of commercially available teas on osteoblasts: green, black and rooibos tea. Tea was normalized to 1 or 10 MUg per mL gallic acid equivalents to assess differences in outcomes based on tea profiles rather than the quantity of polyphenol naturally present. The lower level of polyphenols (1 MUg per mL gallic acid equivalents) - regardless of tea type and thus polyphenol profile - resulted in greater mineral content as well as cellular and alkaline phosphatase activity in Saos2 cells. Moreover, this was associated with higher markers of differentiation (osteopontin, sclerostin) and reduced cellular toxicity and pro-inflammatory markers (IL6, TNFalpha). Green, black and rooibos tea improved osteoblast activity at the low level and support epidemiological evidence suggesting tea consumption may benefit bone heath. PMID- 26885716 TI - Clonality of localized and metastatic prostate cancer. AB - PURPOSE OF REVIEW: The influence of the long life-history of prostate cancer on the temporal and spatial variability of the tumour genome is now being elucidated. Multiregion sequencing to identify spatio-genomic differences in prostate tumour mutation profiles combined with computational approaches can map the evolution and transit of tumour cells throughout an individual patient. RECENT FINDINGS: A series of recent studies have demonstrated that a prostate tumour is often composed of different subclones, with varying genetic similarity. As such, a single biopsy specimen may be insufficient to make accurate clinical predictions from molecular biomarkers, greatly complicating the application of biopsy-based tools for precision medicine. In addition, subclones that arise outside of the primary tumour can seed new metastases and circulate between sites within a patient. SUMMARY: The mutational complexity of multiple tumour clones within the same individual, which respond differently to specific treatments, suggests the need for multimodal interventions. PMID- 26885718 TI - Using SBAR as a Preconference Reporting Tool for Nursing Students. PMID- 26885719 TI - Teaching Psychomotor Skills in Nursing. PMID- 26885717 TI - Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. AB - The kinase Bub1 functions in the spindle assembly checkpoint (SAC) and in chromosome congression, but the role of its catalytic activity remains controversial. Here, we use two novel Bub1 inhibitors, BAY-320 and BAY-524, to demonstrate potent Bub1 kinase inhibition both in vitro and in intact cells. Then, we compared the cellular phenotypes of Bub1 kinase inhibition in HeLa and RPE1 cells with those of protein depletion, indicative of catalytic or scaffolding functions, respectively. Bub1 inhibition affected chromosome association of Shugoshin and the chromosomal passenger complex (CPC), without abolishing global Aurora B function. Consequently, inhibition of Bub1 kinase impaired chromosome arm resolution but exerted only minor effects on mitotic progression or SAC function. Importantly, BAY-320 and BAY-524 treatment sensitized cells to low doses of Paclitaxel, impairing both chromosome segregation and cell proliferation. These findings are relevant to our understanding of Bub1 kinase function and the prospects of targeting Bub1 for therapeutic applications. PMID- 26885720 TI - Plasma pentraxin-3 levels in patients with Takayasu's arteritis during routine follow-up. AB - OBJECTIVES: To date, no biomarker is universally accepted to be a surrogate for active disease being one of major difficulties in follow-up of Takayasu's arteritis (TAK). In this study, we aimed to investigate plasma pentraxin-3 (PTX 3) levels and its correlation with activity in patients with TAK. METHODS: This cross-sectional study included 94 patients (age: 43.3+/-13.6 years, F/M: 80/14) with TAK, 40 age-sex matched control donors (age: 41.5+/-9.3 years, F/M: 28/12). TAK patients were evaluated by physician's global assessment (PGA; active/inactive), as well as with the activity definition by Kerr et al. and with a new composite index of ITAS2010 (Indian Takayasu Clinical Activity Score). Plasma PTX-3 levels are measured with an enzyme linked immunosorbent assay kit. RESULTS: Thirty-three (35.5%) patients were clinically active with PGA, while 25 (31.6%) patients and 28 (31.8%) patients were accepted to have active disease according to Kerr activity criteria and ITAS2010, respectively. Plasma PTX-3 levels were significantly higher in TAK patients compared to healthy controls (3.5+/-2.5 ng/ml vs. 2.5+/-1.6 ng/ ml, p=0.029). However, PTX-3 levels were similar among active and inactive patients according to all three assessment tools. PTX-3 levels significantly correlated only with serum CRP levels. CONCLUSIONS: Although plasma PTX- 3 levels were higher in patients with TAK compared to healthy controls, we observed no association with disease activity, limiting the role of PTX-3 level as a biomarker for active disease in TAK. PMID- 26885721 TI - The current pharmacological landscape of tuberculous meningitis: where to next? PMID- 26885722 TI - Nosocomial Infections Caused by Acinetobacter baumannii: Are We Losing the Battle? AB - BACKGROUND: The incidence of nosocomial infections caused by multi-drug- and extended-drug resistant strains of Acinetobacter is constantly increasing all over the world, with a high mortality rate. We analyzed the in-hospital data on the sensitivity of Acinetobacter baumannii isolates and correlated them with antibiotic treatment and clinical outcomes of nosocomial infections over a 17-mo period. METHODS: Retrospective analysis was performed at the Clinical Center "Bezanijska kosa," Belgrade, Serbia. Microbiologic data (number and sensitivity of A. baumannii isolates) and clinical data (medical records of 41 randomly selected patients who developed nosocomial infection caused by A. baumannii) were matched. RESULTS: Acinetobacter baumannii, detected in 279 isolates and obtained from 19 patients (12% of all samples), was resistant to almost all antibiotics tested, including carbapenems, with the exception of colistin and tigecycline. It was obtained most often from the respiratory tract samples. Empiric treatment of the nosocomial infections (pneumonia in 75% of cases) involved cephalosporins, metronidazole, and carbapenems (80%, 66%, and 61% of patients, respectively), whereas tigecyclin and colistin were used primarily in targeted therapy (20% and 12% of patients, respectively). The mortality rate of patients treated empirically was significantly higher (p < 0.01), reaching 100% in the elderly. CONCLUSIONS: Nosocomial A. baumannii infections represent a significant clinical problem because of their high incidence, lack of susceptibility to the most commonly used antibiotics, and the often inappropriate treatment, which favors the development of multi-drug-resistant strains. PMID- 26885723 TI - Efficient Fabrication of Hierarchically Porous Graphene-Derived Aerogel and Its Application in Lithium Sulfur Battery. AB - Hierarchically porous carbon/graphene aerogel (CGA) with relatively high surface area and pore volume is synthesized through an efficient fabrication strategy, which involves forming hydrothermal carbon layer on the pore wall as upholder and directly carbonizing the wet hydrogel from hydrothermal reaction, without using any special drying techniques. Cassava powder is used as carbon precursor which enables sustainable synthesis. Carbonizing the wet hydrothermal product is found to be a self-activation process, through which abundant pores are generated. The aerogel is used as host to encapsulate sulfur for lithium sulfur battery. Graphene, served as highly conductive scaffold, accelerates the transport of the electrons. The hierarchically porous structure is in favor of improving the electrochemical performance of lithium sulfur battery. Therefore, the cathode with high sulfur loading and high sulfur content can deliver very good performance. PMID- 26885724 TI - A successful case of second autologous haematopoietic stem cell transplantation for post-transplant systemic sclerosis relapse. PMID- 26885727 TI - Analysis of Confined Random Walkers with Applications to Processes Occurring in Molecular Aggregates and Immunological Systems. AB - Explicit solutions are presented in the Laplace and time domains for a one variable Fokker-Planck equation governing the probability density of a random walker moving in a confining potential. Illustrative applications are discussed in two unrelated physical contexts: quantum yields in a doped molecular crystal or photosynthetic system, and the motion of signal receptor clusters on the surface of a cell encountered in a problem in immunology. An interesting counterintuitive effect concerning the consequences of confinement is found in the former, and some insights into the driving force for microcluster centralization are gathered in the latter application. PMID- 26885726 TI - Enhancing Mn(II)-Binding and Manganese Peroxidase Activity in a Designed Cytochrome c Peroxidase through Fine-Tuning Secondary-Sphere Interactions. AB - Noncovalent second-shell interactions are important in controlling metal-binding affinity and activity in metalloenzymes, but fine-tuning these interactions in designed metalloenzymes has not been fully explored. As a result, most designed metalloenzymes have low metal-binding affinity and activity. Here we identified three mutations in the second coordination shell of an engineered Mn(II)-binding site in cytochrome c peroxidase (called MnCcP.1, containing Glu45, Glu37, and Glu181 ligands) that mimics the native manganese peroxidase (MnP), and explored their effects on both Mn(II)-binding affinity and MnP activity. First, removing a hydrogen bond to Glu45 through Tyr36Phe mutation enhanced Mn(II)-binding affinity, as evidenced by a 2.8-fold decrease in the KM of Mn(II) oxidation. Second, introducing a salt bridge through Lys179Arg mutation improved Glu35 and Glu181 coordination to Mn(II), decreasing KM 2.6-fold. Third, eliminating a steric clash that prevented Glu37 from orienting toward Mn(II) resulted in an 8.6 fold increase in kcat/KM, arising primarily from a 3.6-fold decrease in KM, with a KM value comparable to that of the native enzyme (0.28 mM vs 0.19 mM for Pleurotus eryngii MnP PS3). We further demonstrated that while the effects of Tyr36Phe and Lys179Arg mutations are additive, because involved in secondary shell interactions to different ligands, other combinations of mutations were antagonistic because they act on different aspects of the Mn(II) coordination at the same residues. Finally, we showed that these MnCcP variants are functional models of MnP that mimic its activity in both Mn(II) oxidation and degradation of a phenolic lignin model compound and kraft lignin. In addition to achieving KM in a designed protein that is similar to the that of native enzyme, our results offer molecular insight into the role of noncovalent interactions around metal binding sites for improving metal binding and overall activity; such insight can be applied to rationally enhance these properties in other metalloenzymes and their models. PMID- 26885728 TI - Risk of Major Adverse Cardiovascular Events and All-Cause Mortality in Patients With Hidradenitis Suppurativa. AB - IMPORTANCE: Hidradenitis suppurativa (HS) is a common inflammatory skin disease. The disease has been associated with cardiovascular (CV) risk factors, but the risk of CV disease in patients with HS is unknown. OBJECTIVE: To investigate CV risk in patients with HS. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study was conducted from January 1, 1997, to December 31, 2011, using individual-level linkage of nationwide administrative registers. In a study population of 35 368 Danish individuals, 5964 patients aged 18 years or older with a hospital-based diagnosis of HS (cases) were matched 1:5 on age, sex, and calendar time with 29 404 individuals serving as controls. MAIN OUTCOMES AND MEASURES: Outcomes were myocardial infarction (MI), stroke, CV-associated death, major adverse CV events (MACEs), and all-cause mortality. Incidence rate ratios (IRRs) were estimated by Poisson regression. RESULTS: The 5964 patients with HS had a mean (SD) age of 37.7 (11.7) years; 4346 (72.9%) were women. In this sample, a total of 62 (42 749.0 person-years) MIs, 74 (42 647.8 person-years) ischemic strokes, 63 (42 941.7 person-years) CV-associated deaths, 169 (42 463.5 person-years) MACEs, and 231 (42 941.7 person-years) all-cause deaths occurred during follow-up. Adjusted (age, sex, socioeconomic status, smoking, comorbidity, and medication) IRRs (95% CIs) were 1.57 (1.14-2.17) for MI, 1.33 (1.01-1.76) for ischemic stroke, 1.95 (1.42-2.67) for CV-associated death, 1.53 (1.27-1.86) for MACEs, and 1.35 (1.15-1.59) for all-cause mortality. When patients with severe psoriasis were used as controls, the adjusted IRRs in patients with HS were 1.00 (0.74-1.35) for MI, 0.93 (0.71-1.22) for ischemic stroke, 1.58 (1.17-2.12) for CV associated death, 1.08 (0.90-1.29) for MACEs, and 1.09 (0.94-1.28) for all-cause mortality. CONCLUSIONS AND RELEVANCE: Hidradenitis suppurativa was associated with a significantly increased risk of adverse CV outcomes and all-cause mortality independent of measured confounders. The risk of CV-associated death was higher in patients with HS compared with the risk in those with severe psoriasis. The results call for increased awareness of this association and for studies of its clinical consequences. PMID- 26885729 TI - Barriers to Participation in Preoperative Risk-Reduction Programs Prior to Ventral Hernia Repair: An Assessment of Underserved Patients at a Safety-Net Hospital. PMID- 26885730 TI - Science to Practice: Hyperpolarized Metabolic MR Imaging--The Light at the End of the Tunnel for Clinical (13)C MR Spectroscopy? AB - Hyperpolarized metabolic magnetic resonance (MR) imaging offers greatly enhanced sensitivity to multinuclear MR spectroscopy, opening up a new tool with which to noninvasively assess metabolic changes in the diseased heart. In this issue of Radiology, O h-Ici et al ( 1 ) have demonstrated this ability by exploring the metabolic changes that occur in the setting of ischemia-reperfusion. They have shown the acute metabolic alterations that occur immediately after reperfusion (increased anaerobic and decreased oxidative metabolism) that then normalize over the following 60 minutes. This demonstration paves the way for the use of hyperpolarized metabolic MR imaging in the assessment of coronary artery disease in humans and shows the potential for this new tool to aid in the assessment of the diseased heart. PMID- 26885731 TI - Recent Endovascular Trials: Implications for Radiology Departments, Radiology Residency, and Neuroradiology Fellowship Training at Comprehensive Stroke Centers. PMID- 26885732 TI - Pelvic Evaluation in Thoracolumbar Corrective Spine Surgery: How I Do It. AB - Surgeons and radiologists have traditionally focused on frontal radiographs and the measurement of scoliosis curves as important tools in the management of spinal deformity. It has become evident, however, that the management of spinal deformity should use a multidimensional approach with an increased emphasis on standing lateral radiographs and the sagittal position of the spine. Furthermore, they have come to realize the critical role that the pelvis plays in the maintenance of posture. Failure to recognize pelvic compensation can lead to under-treatment and poor postoperative outcomes. PMID- 26885725 TI - Systems Biology Approaches for Host-Fungal Interactions: An Expanding Multi-Omics Frontier. AB - Opportunistic fungal infections are an increasing threat for global health, and for immunocompromised patients in particular. These infections are characterized by interaction between fungal pathogen and host cells. The exact mechanisms and the attendant variability in host and fungal pathogen interaction remain to be fully elucidated. The field of systems biology aims to characterize a biological system, and utilize this knowledge to predict the system's response to stimuli such as fungal exposures. A multi-omics approach, for example, combining data from genomics, proteomics, metabolomics, would allow a more comprehensive and pan optic "two systems" biology of both the host and the fungal pathogen. In this review and literature analysis, we present highly specialized and nascent methods for analysis of multiple -omes of biological systems, in addition to emerging single-molecule visualization techniques that may assist in determining biological relevance of multi-omics data. We provide an overview of computational methods for modeling of gene regulatory networks, including some that have been applied towards the study of an interacting host and pathogen. In sum, comprehensive characterizations of host-fungal pathogen systems are now possible, and utilization of these cutting-edge multi-omics strategies may yield advances in better understanding of both host biology and fungal pathogens at a systems scale. PMID- 26885733 TI - State of the Art: Clinical Applications of Cardiac T1 Mapping. AB - While cardiovascular magnetic resonance (MR) has become the noninvasive tool of choice for the assessment of myocardial viability and for the detection of acute myocardial edema, cardiac T1 mapping is believed to further extend the ability of cardiovascular MR to characterize the myocardium. Fundamentally, cardiovascular MR can improve diagnosis of disease that historically has been challenging to establish with other imaging modalities. For example, decreased native T1 values appear highly specific to detect and quantify disease severity related to myocardial iron overload states or glycosphingolipid accumulation in Anderson Fabry disease, whereas high native T1 values are observed with edema, amyloid, and other conditions. Cardiovascular MR can also improve the assessment of prognosis with parameters that relate to myocardial structure and composition that complement the familiar functional parameters around which contemporary cardiology decision making revolves. In large cohorts, extracellular volume fraction (ECV) has been shown to quantify the full extent of myocardial fibrosis in noninfarcted myocardium. ECV may predict outcomes at least as effectively as left ventricular ejection fraction. This uncommon statistical observation (of potentially being more strongly associated with outcomes than ejection fraction) suggests prime biologic importance for the cardiac interstitium that may rank highly in the hierarchy of vast myocardial changes occurring in cardiac pathophysiology. This article presents current and developing clinical applications of cardiac T1 mapping and reviews the existing evidence on their diagnostic and prognostic value in various clinical conditions. This article also contextualizes these advances and explores how T1 mapping and ECV may affect major "global" issues such as diagnosis of disease, risk stratification, and paradigms of disease, and ultimately how we conceptualize patient vulnerability. PMID- 26885736 TI - Case 227: Endobronchial Carcinoid Tumor with Incidental Metastatic Breast Cancer Detected with Somatostatin Receptor Scintigraphy ((111)In Pentreotide). AB - HISTORY: A 30-year-old woman with polycystic ovarian syndrome who was undergoing hormone replacement therapy presented with a 6-month history of a nonproductive cough and a 1-day history of hemoptysis (approximately 20 mL). Intravenous contrast material-enhanced (100 mL of Omnipaque 350; GE Healthcare, Princeton, NJ) computed tomographic (CT) pulmonary angiography was performed to evaluate for pulmonary embolism. On the basis of the CT pulmonary angiographic findings, chromogranin A and 5-hydroxyindoleacetic acid levels were measured and were 7 nmol/L (343 ug/L) (high) and 2.9 mg per 24 hours (15.167 umol/d) (normal), respectively. This patient underwent bronchoscopy and biopsy. After these tests, she was referred for whole-body scintigraphy, which revealed an unexpected finding that was further investigated with fluorine 18 ((18)F) flurodeoxyglucose (FDG) positron emission tomography (PET) and CT. PMID- 26885737 TI - James Lean Body Weight Formula Is Not Appropriate for Determining CT Contrast Media Dose in Patients with High Body Mass Index. PMID- 26885738 TI - Severe Bleeding after Percutaneous Transhepatic Drainage of the Biliary System. PMID- 26885739 TI - Role of Coronary CT Angiography in Patients with Stroke. PMID- 26885740 TI - Potential Solution for the Age-Old Problem of CT Overuse in Emergency Departments? PMID- 26885741 TI - Radiology Transitions in the Lion City. PMID- 26885742 TI - Effect of Change in Portal Venous Blood Flow Rates on the Performance of a 2.45 GHz Microwave Ablation Device. PMID- 26885743 TI - Image Noise Reduction Algorithm for Digital Subtraction Angiography: Clinical Results. PMID- 26885745 TI - Roaming Under the Microscope: Trajectory Study of Formaldehyde Dissociation. AB - The photodissociation of formaldehyde was studied using quasi-classical trajectories to investigate "roaming," or events involving trajectories that proceed far from the minimum energy pathway. Statistical analysis of trajectories performed over a range of nine excitation energies from 34 500 to 41 010 cm(-1) (including zero-point energy) provides characterization of the roaming phenomenon and insight into the mechanism. The trajectories are described as projections onto three coordinates: the distance from the CO center of mass to the furthest H atom and the azimuthal and polar coordinates of that H atom with respect to the CO axis. The trajectories are used to construct a "minimum energy" potential energy surface showing the potential for any binary combination of these three coordinates that is at a minimum energy with respect to values of the other coordinates encountered during the trajectories. We also construct flux diagrams for roaming, transition-state, and radical pathways, as well as "reaction configuration" plots that show the distribution of reaction geometries for roaming and transition-state pathways. These constructs allow characterization of roaming in formaldehyde as, principally, internal rotation of the roaming H atom around the CO axis at a slowly varying and elongated distance from the CO center of mass. The rotation is nearly uniform, and is sometimes accompanied by rotation in the polar coordinate. The roaming state of formaldehyde can be treated as a separate kinetic entity, much as one might treat an isomer. Rate constants for the formation of and reaction from this roaming state are derived from the trajectory data as a function of excitation energy. PMID- 26885746 TI - Sexual and Romantic Relationships: Experiences of Adolescent and Young Adult Cancer Survivors. AB - This study examined the quality and satisfaction of sexual/romantic relationships of adolescents/young adults (AYAs) who recently completed cancer treatment. AYAs between 16 and 26 years old (62.5% female) and less than 24 months post-treatment were interviewed using the Psychosocial Adjustment to Illness Scale (PAIS) interview. Of 43 participants, 16 (37.2%) were in a relationship at time of the interview; eight (50%) reported minor relationship/sexual difficulties. AYAs identified emotional support with their partner as positive aspects of their relationships, and described relational conflict associated with communication difficulties and loss of sexual interest. Better understanding the factors that enable healthy relationships warrants further exploration. PMID- 26885747 TI - Tensile Strength of Liquids: Equivalence of Temporal and Spatial Scales in Cavitation. AB - It is well known that strain rate and size effects are both important in material failure, but the relationships between them are poorly understood. To establish this connection, we carry out molecular dynamics (MD) simulations of cavitation in Lennard-Jones and Cu liquids over a very broad range of size and strain rate. These studies confirm that temporal and spatial scales play equivalent roles in the tensile strengths of these two liquids. Predictions based on smallest-scale MD simulations of Cu for larger temporal and spatial scales are consistent with independent simulations, and comparable to experiments on liquid metals. We analyze these results in terms of classical nucleation theory and show that the equivalence arises from the role of both size and strain rate in the nucleation of a daughter phase. Such equivalence is expected to hold for a wide range of materials and processes and to be useful as a predictive bridging tool in multiscale studies. PMID- 26885748 TI - Improving the management and care of refugees in Australian hospitals: a descriptive study. AB - Objectives The aim of the present study was to investigate healthcare provider perceptions of the impact of refugee patients at two public hospitals, one rural and one urban, in designated refugee resettlement areas. Healthcare professionals' views regarding improvements that could be made in this area were also sought. Methods Two-page anonymous questionnaires containing demographic, quantitative and open-ended questions were distributed to 150 healthcare providers at each research site. Results Response rates at the rural and urban sites were 50% and 49%, respectively. Refugees were seen at least monthly by 40% of respondents. Additional support was requested by 70% of respondents. Confidence was associated with being born overseas (P=0.029) and increased time working with refugees (rs=0.418, P<0.001). Only 47% of respondents felt confident managing social and psychological needs of refugees. Midwives saw refugees more than nursing and allied healthcare staff combined, and this was significant at the rural hospital (P<0.001). Rural respondents reported that working with refugees enhanced their practice (P=0.025), although felt significantly less confident (P<0.001) than urban respondents. Themes that arose regarding barriers to care included language and cultural barriers, paucity of knowledge and issues accessing available services, including appropriate interpreters, Medicare eligibility and patient factors, including lack of patient trust in government systems. Desire for support was more pronounced in the rural setting (P=0.001). Conclusions Refugees were seen frequently in both settings and most respondents requested additional support, highlighting that caring for refugees in Australian hospitals is a significant challenge. Additional support and education should be targeted to those caring for refugees most frequently, particularly midwifery services, to reduce barriers to care. What is known about the topic? Refugees are a vulnerable group, often with complex health needs. These needs are often unmet because of issues including language and cultural barriers. What does this paper add? Refugees were seen frequently in the two public hospital settings involved in the present study and most often by midwifery services. Healthcare professionals require more support, more information about available services and better access to interpreter services. These issues were more pronounced in the rural setting where very limited research exists. What are the implications for practitioners? Implementing additional support and education regarding refugee health needs could increase knowledge and confidence when managing refugees, reducing barriers to care and improving quality of care. PMID- 26885749 TI - Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient. AB - Docetaxel comprises one of the most effective anti-cancer drugs despite of serious side effects. Liposomes encapsulation is practically feasible to deliver the drug. However, due to the significant hydrophobicity, docetaxel will be integrated into the lipid bilayer resulting in poor encapsulation capacity. Here, we evaluated a remote loading strategy using a solubility gradient made between the two solvents for 7-glucosyloxyacetyldocetaxel, which has enhanced water solubility of docetaxel with a coupled glucose moiety. Therefore, 7 glucosyloxyacetyldocetaxel was more effectively encapsulated into liposomes with 71.0% of encapsulation efficiency than docetaxel. While 7 glucosyloxyacetyldocetaxel exhibited 90.9% of tubulin stabilisation activity of docetaxel, 7-glucosyloxyacetyldocetaxel encapsulated in liposomes significantly inhibited the growth of tumour in vivo with side effects less than unencapsulated drug. Collectively, the encapsulation of 7-glucosyloxyacetyldocetaxel into liposomes by remote loading under the solubility gradient is considered to be a promising application to prepare practical drug delivery system. PMID- 26885750 TI - A new anti-proliferative acylated flavonol glycoside from Fuzhuan brick-tea. AB - Fuzhuan brick-tea (FBT) is unique for a fungal fermentation stage in its manufacture process and is classified in dark tea. A new acylated flavonol glycoside, kaempferol 3-O-[E-p-coumaroyl-(->2)][alpha-l-arabinopyranosyl-(1 >3)][alpha-l-rhamnopyranosyl(1->6)]-beta-d-glucopyranoside, which was trivially named as camellikaempferoside A (1), was isolated from FBT along with camelliquercetiside C (2). Their structures were unambiguously elucidated by combination of spectroscopic and chemical methods. Compound 1 showed anti proliferative activity against MCF-7 and MDA-MB-231 cells with IC50 values of 7.83 and 19.16 MUM, respectively. PMID- 26885751 TI - Multi-objective analysis for assessing simultaneous changes in regional spinal curvatures under backpack carriage in young adults. AB - Change in sagittal spinal curvature from the neutral upright stance is an important measure of the heaviness and correctness of backpack use. As current recommendations, with respect to spinal profile, of backpack load thresholds were based on the significant curvature change in individual spinal region only, this study investigated the most critical backpack load by assessing simultaneously the spinal curvature changes along the whole spine. A motion analysis system was used to measure the curvature changes in cervical, upper thoracic, lower thoracic and lumbar regions with backpack load at 0, 5, 10, 15 and 20% of body weight. A multi-objective goal programming model was adopted to determine the global critical load of maximum curvature change of the whole spine in accordance with the maximum curvature changes of the four spinal regions. Results suggested that the most critical backpack load was 13% of body weight for healthy male college students. Practitioner Summary: As current recommendations of backpack load thresholds were based on the significant curvature change in individual spinal region only, this study investigated the backpack load by considering simultaneously the spinal curvature changes along the whole spine. The recommendation, in terms of the global critical load, was 13% of body weight for healthy male college students. PMID- 26885752 TI - SOX9 indirectly regulates CEACAM1 expression and immune resistance in melanoma cells. AB - As melanoma cells are immunogenic, they instigate an adaptive immune response and production of anti-tumor T-cells. A central factor in this interaction is CEACAM1 (carcinoembryonic antigen cell adhesion molecule 1), a transmembrane glycoprotein previously shown in our lab to protect melanoma cells from T cell-mediated killing. In this study, we examine the role of transcription factor SOX9 in the regulation of CEACAM1 expression and immune resistance in melanoma cells. Knockdown of endogenous SOX9 results in CEACAM1 up-regulation, while its overexpression leads to the opposite effect. We show that SOX9 controls CEACAM1 expression at a transcriptional level, but in an indirect manner, as regulation of the CEACAM1 promoter remains intact even when all eight potential SOX9-binding sites are abolished. A series of promoter truncations localizes the SOX9 controlled area to the proximal 200bp of the promoter. Point mutations in putative Sp1 and ETS1 binding sites identify these transcription factors as the primary SOX9-controlled mediators. Co-immunoprecipitation studies show that SOX9 and Sp1 physically interact in melanoma cells, while silencing of SOX9 down regulates ETS1, but not Sp1, in the same cells. Finally, knockdown of SOX9 indeed renders melanoma cells resistant to T cell-mediated killing, in line with the increased CEACAM1 expression. In conclusion, we show that SOX9 regulates CEACAM1 expression in melanoma cells, and thereby their immune resistance. As CEACAM1 is a pivotal protein in melanoma biology and immune crosstalk, further understanding of its regulation can provide new insights and contribute to the development of novel approaches to therapy. PMID- 26885753 TI - Potential role of PCTAIRE-2, PCTAIRE-3 and P-Histone H4 in amyloid precursor protein-dependent Alzheimer pathology. AB - Amyloid Precursor Protein (APP) is regulated in a mitosis-specific manner and plays a role in proliferative signaling in cells. Though APP-derived Abeta generation has a well-established role in neurodegeneration, the mechanistic role of APP in this process is not fully understood. Here, we performed an unbiased, comprehensive analysis of the phosphoproteome signature in APP-null neuroblastoma cells (B103) compared to those expressing APP-695 isoform (B103-695) to determine if APP expression affects protein phosphorylation. Stable isotope labeling by amino acids in cell culture (SILAC) followed by mass spectrometry-based phosphoproteomic analysis with PolyMAC identified a total of 2,478 phosphopeptides in the B103 and B103-695 cell culture model system. We observed that phosphorylation of PCTAIRE-2 (CDK17), PCTAIRE-3 (CDK18), and Histone H4 are significantly elevated in B103-695 cells; western blot analysis confirmed overexpression of PCTAIREs and increased phosphorylation of Histone H4. More importantly, analysis of primary neurons treated with Abeta, as well as brain samples from MCI (mild cognitive impaired) and AD patients recapitulated these results, showing increased levels of PCTAIREs and P-Histone H4. These novel findings identify a hitherto uncharacterized mechanism by which APP and/or Abeta may promote AD neurodegeneration, and raises the possibility that their inhibition may protect against pathology development in AD. PMID- 26885755 TI - Molecular signatures of age-associated chronic degeneration of shoulder muscles. AB - Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder's rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration. PMID- 26885754 TI - Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats. AB - The effect of exercise on wound healing in aging tendon was tested using a rat moderate treadmill running (MTR) model. The rats were divided into an MTR group that ran on a treadmill for 4 weeks and a control group that remained in cages. After MTR, a window defect was created in the patellar tendons of all rats and wound healing was analyzed. We found that MTR accelerated wound healing by promoting quicker closure of wounds, improving the organization of collagen fibers, and decreasing senescent cells in the wounded tendons when compared to the cage control. MTR also lowered vascularization, increased the numbers of tendon stem/progenitor cells (TSCs) and TSC proliferation than the control. Besides, MTR significantly increased the expression of stem cell markers, OCT-4 and Nanog, and tenocyte genes, Collagen I, Collagen III and tenomodulin, and down regulated PPAR-gamma, Collagen II and Runx-2 (non-tenocyte genes). These findings indicated that moderate exercise enhances healing of injuries in aging tendons through TSC based mechanisms, through which exercise regulates beneficial effects in tendons. This study reveals that appropriate exercise may be used in clinics to enhance tendon healing in aging patients. PMID- 26885756 TI - Epigenetic clock analyses of cellular senescence and ageing. AB - A confounding aspect of biological ageing is the nature and role of senescent cells. It is unclear whether the three major types of cellular senescence, namely replicative senescence, oncogene-induced senescence and DNA damage-induced senescence are descriptions of the same phenomenon instigated by different sources, or if each of these is distinct, and how they are associated with ageing. Recently, we devised an epigenetic clock with unprecedented accuracy and precision based on very specific DNA methylation changes that occur in function of age. Using primary cells, telomerase-expressing cells and oncogene-expressing cells of the same genetic background, we show that induction of replicative senescence (RS) and oncogene-induced senescence (OIS) are accompanied by ageing of the cell. However, senescence induced by DNA damage is not, even though RS and OIS activate the cellular DNA damage response pathway, highlighting the independence of senescence from cellular ageing. Consistent with this, we observed that telomerase-immortalised cells aged in culture without having been treated with any senescence inducers or DNA-damaging agents, re-affirming the independence of the process of ageing from telomeres and senescence. Collectively, our results reveal that cellular ageing is distinct from cellular senescence and independent of DNA damage response and telomere length. PMID- 26885760 TI - Correction to Caylobolide B, a Macrolactone from Symplostatin 1-Producing Marine Cyanobacteria Phormidium spp. from Florida. PMID- 26885757 TI - Prognosis communication with older patients with multimorbidity: Assessment after an educational intervention. AB - This study aimed to assess how internal medicine residents incorporated prognosis to inform clinical decisions and communicated prognosis in primary care visits with older patients with multimorbidity after an educational intervention, and resident and patient perspectives regarding these visits. Assessment used mixed methods. The authors assessed the frequency and content of prognosis discussions through residents' self-report and qualitative content analysis of audio-recorded clinic visits. The authors assessed the residents' perceived effect of incorporating prognosis on patient care and patient relationship through a resident survey. The authors assessed the patients' perceived quality of communication and trust in physicians through a patient survey. The study included 21 clinic visits that involved 12 first-year residents and 21 patients. Residents reported incorporating patients' prognoses to inform clinical decisions in 13/21 visits and perceived positive effects on patient care (in 11/13 visits) and patient relationship (in 7/13 visits). Prognosis communication occurred in 9/21 visits by self-report, but only in six of these nine visits by content analysis of audio-recordings. Patient ratings were high regardless of whether or not prognosis was communicated. In summary, after training, residents often incorporated patients' prognoses to inform clinical decisions, but sometimes did so without communicating prognosis to the patients. Residents and patients reported positive perceptions regarding the visits. PMID- 26885758 TI - Selenium status during pregnancy and child psychomotor development-Polish Mother and Child Cohort study. AB - BACKGROUND: The studies on the impact of selenium (Se) levels in different pregnancy periods on child psychomotor functions are limited. The aim of this study was to evaluate the impact of prenatal Se on child neurodevelopment. METHODS: The study population consisted of 410 mother-child pairs from Polish Mother and Child Cohort. Se levels were measured in each trimester of pregnancy, at delivery, and in cord blood by graphite furnace atomic absorption spectrometry. Psychomotor development was assessed in children at the age of 1 and 2 y using the Bayley Scales of Infant and Toddler Development. RESULTS: Plasma Se levels decreased through pregnancy (from 48.3 +/- 10.6 ug/l in the first trimester to 38.4 +/- 11.8 ug/l at delivery; P < 0.05). A statistically significant positive association between Se levels in the first trimester of pregnancy and motor development (beta = 0.2, P = 0.002) at 1 y of age, and language development (beta = 0.2, P = 0.03) at 2 y of age was observed. The positive effect of Se levels on cognitive score at 2 y of age was of borderline significance (beta = 0.2, P = 0.05). CONCLUSION: Prenatal selenium status was associated with child psychomotor abilities within the first years of life. Further epidemiological and preclinical studies are needed to confirm the association and elucidate the underlying mechanisms of these effects. PMID- 26885761 TI - Pattern dystrophy in a female carrier of RP2 mutation. PMID- 26885762 TI - The Effects of Nitrate-Rich Supplementation on Neuromuscular Efficiency during Heavy Resistance Exercise. AB - OBJECTIVE: Nitrate-rich (NR) supplements can enhance exercise performance by improving neuromuscular function and the aerobic cost of exercise. However, little is known about the effects of nitrate on dynamic, multijoint resistance exercise. METHODS: Fourteen resistance-trained men (age, 21.1 +/- 0.9 years; height, 173.2 +/- 2.9 cm: body mass, 77.6 +/- 4.3 kg; squat one-repetition maximum [1RM], 127.5 +/- 18.8 kg) participated in a randomized, double-blind, crossover experiment. Subjects consumed an NR or nitrate-poor (NP) supplement for 3 days, performed a bout of heavy resistance exercise, completed a washout, and then repeated the procedures with the remaining supplement. Before, during, and after exercise, individual and gross motor unit efficiency was assessed during isometric and dynamic muscle contractions. In addition, we compared physical performance, heart rate, lactate, and oxygen consumption (VO2). RESULTS: Nitrate rich supplementation resulted in lower initial muscle firing rates at rest and lower mean and maximum firing rates over the course of fatiguing exercise. Nitrate-poor supplementation was accompanied by increased mean and maximum firing rates by the end of exercise and lower initial firing rates. In addition, NR supplementation resulted in higher mean peak electromyography (EMG) amplitudes. Heart rate, lactate, and physical performance did not differ by treatment, but oxygen consumption increased more frequently when the NP supplement was consumed. CONCLUSION: Supplementation with an NR beetroot extract-based supplement provided neuromuscular advantages during metabolically taxing resistance exercise. PMID- 26885764 TI - Insulin Infusion Sets: A Critical Reappraisal. AB - An insulin infusion set (IIS) is a key component of insulin pumps. In daily practice issues with the IIS appear to be as relevant for a successful insulin therapy as the pumps themselves. The insulin is applied to the subcutaneous tissue via a Teflon((r)) (Dupont, Wilmington, DE) or steel cannula. There are intensive discussions about the impact the choice of material for insulin application has on insulin pharmacokinetics. In this review, this factor and others that are known to have an impact on the successful usage of IIS are discussed. PMID- 26885759 TI - Evaluation of novel urinary tract infection biomarkers in children. AB - BACKGROUND: Pediatricians frequently use urinalysis to diagnose urinary tract infection (UTI) while awaiting urine culture results, but sensitivity and specificity of urinalysis are limited. This study evaluated the diagnostic accuracy of the antimicrobial peptides (AMPs) human alpha-defensin 5 (HD5) and human neutrophil peptides (HNP) 1-3 as novel UTI biomarkers in children. METHODS: We prospectively enrolled 199 pediatric Emergency Department or Urgent Care patients evaluated for a UTI. Urine concentrations of HD5 and HNP1-3 were measured by enzyme-linked immunosorbent assay. Urine culture was the reference standard. Sensitivities and specificities of leukocyte esterase (LE), HD5, HNP1 3, and test combinations were compared. RESULTS: For predicting positive urine culture, the areas under the receiver-operating characteristic curves for HD5 and HNP1-3 were 0.86 (95% confidence interval (CI): 0.81-0.92) and 0.88 (95% CI: 0.82 0.93), respectively. Compared to LE >= trace, the combination test "LE and HD5" increased specificity by 6% (95% CI: 3-10%) without decreasing sensitivity. In the subgroup whose urine was collected by a clean-catch method, combination tests "LE and HD5" and "HD5 and HNP1-3" increased specificity by > 10% compared to LE alone. CONCLUSION: Urine AMP profiles are a promising novel strategy as an adjunct to urinalysis to aid UTI diagnosis in children. PMID- 26885766 TI - X-ray Structure and Properties of the Ferrous Octaethylporphyrin Nitroxyl Complex. AB - The preparation and characterization of the iron octaethylporphyrin nitroxyl ion, [Fe(OEP)(NO)(-)], is reported. The complex was synthesized by the one-electron reduction of Fe(OEP)(NO) using anthracenide as the reducing agent. The compound was isolated as the potassium (2.2.2)cryptand salt. The anion was characterized using X-ray analysis with visible and infrared spectroscopy. The spectral features of the iron nitroxyl complex were consistent with previous literature reports. The important structural changes upon reduction were a significant decrease in the Fe-N-O bond angle from 142 degrees to 127 degrees and an increase in the N-O bond length from that in the starting nitrosyl moiety. The porphyrin ring became significantly less planar upon reduction, but the displacement of the iron atom from the 24-atom plane was essentially unchanged. In spite of the attempt to encapsulate the potassium ion with the (2.2.2)cryptand, significant interaction between K(+) and the oxygen of the nitroxyl were observed, indicating a contact ion pair in the crystal structure. Comparison between the experimental structure and the DFT-calculated parameters were reported. The results are consistent with the Fe-N-O moiety being the site of the reduction, with little evidence for the reduction of the iron itself or the porphyrin ring. The proton NMR spectrum was also obtained, and the chemical shifts were significantly different from other S = 0 metalloporphyrin complexes. These shifts, though, were consistent with the DFT calculations. PMID- 26885765 TI - Toward a comprehensive care of HIV patients: finding a strategy to detect depression in a Spanish HIV cohort. AB - Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D >= 8 or the HADS-T >= 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings. PMID- 26885767 TI - Maximum Spreading of Liquid Drops Impacting on Groove-Textured Surfaces: Effect of Surface Texture. AB - Maximum spreading of liquid drops impacting on solid surfaces textured with unidirectional parallel grooves is studied for drop Weber number in the range 1 100 focusing on the role of texture geometry and wettability. The maximum spread factor of impacting drops measured perpendicular to grooves, betam,? is seen to be less than that measured parallel to grooves, betam,?. The difference between betam,? and betam,? increases with drop impact velocity. This deviation of betam,? from betam,? is analyzed by considering the possible mechanisms, corresponding to experimental observations-(1) impregnation of drop into the grooves, (2) convex shape of liquid-vapor interface near contact line at maximum spreading, and (3) contact line pinning of spreading drop at the pillar edges-by incorporating them into an energy conservation-based model. The analysis reveals that contact line pinning offers a physically meaningful justification of the observed deviation of betam,? from betam,? compared to other possible candidates. A unified model, incorporating all the above-mentioned mechanisms, is formulated, which predicts betam,? on several groove-textured surfaces made of intrinsically hydrophilic and hydrophobic materials with an average error of 8.3%. The effect of groove-texture geometrical parameters on maximum drop spreading is explained using this unified model. A special case of the unified model, with contact line pinning absent, predicts betam,? with an average error of 6.3%. PMID- 26885768 TI - Robust and Porous beta-Diketiminate-Functionalized Metal-Organic Frameworks for Earth-Abundant-Metal-Catalyzed C-H Amination and Hydrogenation. AB - We have designed a strategy for postsynthesis installation of the beta diketiminate (NacNac) functionality in a metal-organic framework (MOF) of UiO topology. Metalation of the NacNac-MOF (I) with earth-abundant metal salts afforded the desired MOF-supported NacNac-M complexes (M = Fe, Cu, and Co) with coordination environments established by detailed EXAFS studies. The NacNac-Fe MOF catalyst, I*Fe(Me), efficiently catalyzed the challenging intramolecular sp(3) C-H amination of a series of alkyl azides to afford alpha-substituted pyrrolidines. The NacNac-Cu-MOF catalyst, I*Cu(THF), was effective in promoting the intermolecular sp(3) C-H amination of cyclohexene using unprotected anilines to provide access to secondary amines in excellent selectivity. Finally, the NacNac-Co-MOF catalyst, I*Co(H), was used to catalyze alkene hydrogenation with turnover numbers (TONs) as high as 700,000. All of the NacNac-M-MOF catalysts were more effective than their analogous homogeneous catalysts and could be recycled and reused without a noticeable decrease in yield. The NacNac-MOFs thus provide a novel platform for engineering recyclable earth-abundant-element-based single-site solid catalysts for many important organic transformations. PMID- 26885770 TI - Selective Area Sublimation: A Simple Top-down Route for GaN-Based Nanowire Fabrication. AB - Post-growth in situ partial SiNx masking of GaN-based epitaxial layers grown in a molecular beam epitaxy reactor is used to get GaN selective area sublimation (SAS) by high temperature annealing. Using this top-down approach, nanowires (NWs) with nanometer scale diameter are obtained from GaN and InxGa1-xN/GaN quantum well epitaxial structures. After GaN regrowth on InxGa1-xN/GaN NWs resulting from SAS, InxGa1-xN quantum disks (QDisks) with nanometer sizes in the three dimensions are formed. Low temperature microphotoluminescence experiments demonstrate QDisk multilines photon emission around 3 eV with individual line widths of 1-2 meV. PMID- 26885769 TI - High Rates of Exclusive Breastfeeding in Both Arms of a Peer Counseling Study Promoting EBF Among HIV-Infected Kenyan Women. AB - BACKGROUND: Exclusive breastfeeding (EBF) is recommended for 6 months after delivery as the optimal infant feeding method and is especially important for prevention of mother-to-child HIV transmission (PMTCT). However, EBF promotion efforts among HIV-infected mothers in sub-Saharan Africa have achieved mixed success and require context-specific interventions. METHODS: HIV-positive, pregnant women from six clinics in Nairobi were enrolled into a clinic-level, before-after counseling intervention study. All women received standard perinatal and HIV care. Women in the intervention arm were offered three counseling sessions that promoted EBF, described its benefits, and explained breastfeeding techniques. Mother-infant pairs were followed until 14 weeks postpartum, with infant HIV testing at 6 weeks. EBF prevalence at 14 weeks postpartum was compared between study arms using log-binomial regression. Proportions of 6-week HIV-free survival and 14-week infant survival were assessed using Cox regression. Risk estimates were adjusted for clinic, relationship status, and antiretroviral therapy. RESULTS: Between 2009 and 2013, 833 women were enrolled of whom 94% planned to practice EBF for 6 months and 95% were taking therapeutic or prophylactic antiretrovirals. Median age was 27 years; median CD4 count was 403 cells/MUL. EBF prevalence at 14 weeks postpartum was 86% in the control and 81% in the intervention group (p = 0.19). No differences were observed between groups for 6-week HIV-free survival and 14-week infant survival. CONCLUSION: Women who received breastfeeding counseling were not more likely to breastfeed exclusively, in part due to high overall EBF prevalence in this study population. The high EBF prevalence is an important finding, given recent efforts to promote EBF in Kenya. PMID- 26885771 TI - MicroRNAs in cardiovascular disease. AB - PURPOSE OF REVIEW: Noncoding RNAs regulate many aspects of cardiovascular biology and are potential therapy targets. In this review, we summarize and highlight current discoveries in the field of microRNAs, a class of noncoding RNAs. RECENT FINDINGS: miRNAs regulate posttranscriptional gene expression and have been shown to control cardiac development, hypertrophy, fibrosis, and regeneration. Of note are the miRNAs that regulate cardiac contractility (for example, miR-25 and miR 22), cardiac regeneration (like miR-302-367 and miR99/100 families), and fibrosis (as miR-125b). Consistently with these roles of miRNAs, pharmacological intervention using anti-miRNA oligonucleotides (antagomirs or LNA-anti-miRs) has been shown to improve cardiac contractility and mitigate fibrosis, alleviating cardiac dysfunction in the setting of heart failure. SUMMARY: miRNAs are crucial regulators of cardiac phenotype and have enthused both basic scientists and clinicians alike. With advancement of technology and better understanding of mechanisms governing miRNA deregulation, we are at the crossroads for deciphering miRNA function and modulating it for therapeutics. PMID- 26885772 TI - Interleukin 18 (IL-18) as a target for immune intervention. AB - Interleukin 18 (IL-18) is a pleiotropic cytokine involved in the regulation of innate and acquired immune response. In the milieu of IL-12 or IL-15, IL-18 is a potent inducer of IFN-gamma in natural killer (NK) cells and CD4 T helper (Th) 1 lymphocytes. However, IL-18 also modulates Th2 and Th17 cell responses, as well as the activity of CD8 cytotoxic cells and neutrophils, in a host microenvironment-dependent manner. It is produced by various hematopoietic and nonhematopoietic cells, including dendritic cells and macrophages. In an organism, bioactivity of the cytokine depends on the intensity of IL-18 production, the level of its natural inhibitory protein - IL-18BP (IL-18 binding protein) and the surface expression of IL-18 receptors (IL-18R) on the responding cells. This review summarizes the biology of the IL-18/IL-18BP/IL-18R system and its role in the host defense against infections. The prospects for IL-18 application in immunotherapeutic or prophylactic interventions in infectious and non-infectious diseases are discussed. PMID- 26885773 TI - Multiplex real-time PCR to identify a possible reinfection with different strains of human cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients. AB - Human cytomegalovirus (HCMV) infection remains the leading cause of serious contagious complications after allogeneic hematopoietic stem cell transplantation. These infections in HCMV-seropositive recipients can be due to reactivation or reinfection. Different HCMV strains were identified by determining the genotypes isolated from repeatedly tested patients. The UL55 sequences encoding viral glycoprotein B (gB) have been chosen as the target gene. The region, in which the gB precursor protein is cleaved into two fragments by a cellular endoprotease, is characterized by genetic variability, and based on that HCMV is classified into four major genotypes: gB1, gB2, gB3 and gB4. Multiplex real-time PCR assay enabled both, HCMV gB genotyping, as well as simultaneous quantitative assessment of the detected genotypes. This study was carried out in 30 transplant recipients, from whom 105 isolates of HCMV DNA were genotyped. In 40% of recipients, a mixed infection with two or three genotypes was detected. Genotype gB1 dominated in general, and characteristically for mixed infections, the genotype gB3 or gB4 was always present. Although there were no significant differences in the load for each genotype, in case of multiple infections, the number of copies of gB1 genotype was significantly higher when compared to a single gB1 infection. In patients with mixed genotypes, chronic HCMV infections and graft versus host disease were observed more often, as well as antiviral treatment was less effective. It was assumed that these adverse effects can be related to the presence of gB3 and gB4 genotypes. PMID- 26885774 TI - Principles and applications of Ligation Mediated PCR methods for DNA-based typing of microbial organisms. AB - A significant number of DNA-based techniques has been introduced into the field of microorganisms' characterization and taxonomy. These genomic fingerprinting methods were developed to detect DNA sequence polymorphisms by using general principles, such as restriction endonuclease analysis, molecular hybridization, and PCR amplification. In recent years, some alternative techniques based on ligation of oligonucleotide adapters before DNA amplification by PCR, known as Ligation-Mediated PCR methods (LM PCR), have been successfully applied for the typing of microorganisms below the species level. These molecular methods include: Amplified Fragment Length Polymorphism (AFLP), Amplification of DNA fragments Surrounding Rare Restriction Sites (ADSRRS), PCR Melting Profiles (PCR MP), Ligation Mediated PCR/Shifter (LM PCR/Shifter), Infrequent-Restriction-Site Amplification (IRS PCR), double digestion Ligation Mediated Suppression PCR (ddLMS PCR). These techniques are now applied more and more often because they involve less time, are comparably inexpensive, and require only standard lab equipment. Here, we present a general review of this group of methods showing their possibilities and limitations. We also identify questions and propose solutions which may be helpful in choosing a particular LM PCR method for the achievement of the required goal. PMID- 26885775 TI - Effect of different wavelengths of light on laccase, cellobiose dehydrogenase, and proteases produced by Cerrena unicolor, Pycnoporus sanguineus and Phlebia lindtneri. AB - Three species of white rot fungi: Cerrena unicolor, Phlebia lindtneri and Pycnoporus sanguineus were cultured in two different media under five different lighting conditions: dark, white, red, blue, and green light. Laccase, cellobiose dehydrogenase, and protease activities were examined in the samples. Blue light efficiently boosted laccase synthesis in C. unicolor and P. sanguineus, whereas the highest activities (20 654 nkat/l) of P. lindtneri laccase were observed when this fungus was maintained in green light. On the contrary, the green light allowed obtaining the highest activities of cellobiose dehydrogenase of C. unicolor and P. lindtneri, while CDH of P. sanguineus seems to be dependent on white light. It is clearly visible that differences in protease activities are noticeable not only between the lights variants but also among the media used. However, high proteases activities are correlated with light variants inducing laccase in Lindeberg and Holm medium. Contrary to the cellulose-based medium, where they are weak in light variants that lead to high CDH activities. PMID- 26885776 TI - Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol. AB - A library of hyperbranched polyglycerols (HPGs) functionalized with different mole fractions of zwitterionic sulfabetaine and cationic quaternary ammonium ligands was synthesized and characterized. A post-polymerization method was employed that utilized double bond moieties on the dendritic HPG for the coupling of thiol-terminated ligands via UV initiated thiol-ene "click" chemistry. The proportions of different ligands were precisely controlled by varying the ligand concentration during the irradiation process. The effect of the polymer library on hemostasis was investigated using whole human blood. It was found that polymer with >=40% of alkenes converted to positive charges and the remainder to sulfabetaines caused hemagglutination at >=1 mg/mL, without causing red blood cell lysis. The quaternary ammonium groups can interact with the negative charged sites on the membranes of erythrocytes, which provides the bioadhesion. The zwitterionic sulfabetaine evidently provides a hydration layer to partially mask the adverse effects that are likely to be caused by cationic moieties. The polymer was also found able to enhance platelet aggregation and activation in a concentration and positive charge density-dependent manner, which would contribute to initiating hemostasis. In a variety of other assays the material was found to be largely biocompatible. The polymer-induced hemostasis is obtained by a process independent of the normal blood clotting cascade but dependent on red blood cell agglutination, where the polymers promote hemostasis by linking erythrocytes together to form a lattice to entrap the cells. PMID- 26885777 TI - Genomic Characterization of a Novel HIV-1 Second-Generation Recombinant Form Originated from CRF01_AE and CRF08_BC in Dali Prefecture of Yunnan Province, China. AB - Yunnan seems to be a "hot spot" region of HIV-1 recombination. CRF01_AE and subtype CRF08_BC are two main HIV-1 clades circulating in Yunnan. We report here a novel HIV-1 second-generation recombinant form originated from CRF01_AE and CRF08_BC. The strain (12YN10551) was isolated from a HIV-positive male infected through heterosexual contact in Dali prefecture of Yunnan province, China. This is the first report of HIV-1 near full-length genomic sequence in Dali. Recombinant analysis shows that 12YN10551 was composed of two well-established circulating recombinant forms (CRF01_AE and CRF08_BC). Two CRF01_AE recombinant fragments were inserted into the CRF08_BC backbone genome in the pol/vif/vpr/tat/rev and nef gene regions, respectively. The discovery and characterization of this new recombinant indicate that intersubtype recombination is continuously generating new forms of HIV-1. More work is needed to better monitor the genetic diversity of HIV-1 in this region. PMID- 26885778 TI - Use of a 4,5-dicyanoimidazolate anion based ionic liquid for the synthesis of iron and silver nanoparticles. AB - Sixteen new ionic liquids (ILs) with tetraethylammonium, 1-butyl-3 methylimidazolium, 3-methyl-1-octylimidazolium and tetrabutylphosphonium cations paired with 2-substituted 4,5-dicyanoimidazolate anions (substituent at C2 = methyl, trifluoromethyl, pentafluoroethyl, N,N'-dimethyl amino and nitro) have been synthesized and characterized by using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA). The effects of cation and anion type and structure of the resulting ILs, including several room temperature ionic liquids (RTILs), are reflected in the crystallization, melting points and thermal decomposition of the ILs. ILs exhibited large liquid and crystallization ranges and formed glasses on cooling with glass transition temperatures in the range of 22 to -71 degrees C. We selected one of the newly designed ILs due to its bigger size, compared to the common conventional IL anion and high electron-withdrawing nitrile group leads to an overall stabilization anion that may stabilize the metal nanoparticles. Stable and better separated iron and silver nanoparticles are obtained by the decomposition of corresponding Fe2(CO)9 and AgPF6, respectively, under N2-atmosphere in newly designed nitrile functionalized 4,5 dicyanoimidazolate anion based IL. Very small and uniform size for Fe nanoparticles of about 1.8 +/- 0.6 nm were achieved without any additional stabilizers or capping molecules. Comparatively bigger size of Ag-nanoparticles was obtained through the reduction of AgPF6 by hydrogen gas. Additionally, the AgPF6 precursor was decomposed under microwave irradiation (MWI), fabricating nut in-shell-like, that is, core-separated-from-shell Ag-nano-structures. PMID- 26885779 TI - Serum Protein Profile Changes in Psoriatic Patients Undergoing Treatment With Infliximab. AB - The therapeutic paradigm in psoriasis includes antitumor necrosis alpha agents that have been proved effective and safe as long-term therapy. Recently, it has been described a correlation between the use of biologic agents and the occurrence of monoclonal gammopathies, which are haematological conditions characterized by clonal plasma cells proliferation producing a monoclonal immunoglobulin that accumulates in the blood. OBJECTIVE: The aim of this study is to detect electrophoretic abnormalities in psoriatic patients undergoing treatment with infliximab. RESEARCH DESIGN AND METHODS: A retrospective study evaluating all charts from the clinic database of all patients treated with infliximab. The evaluation of serum protein profile is routinely performed in the clinical setting during biologic therapies. We reported the occurrence MGUS in infliximab-treated patients. RESULTS: The study analysis included 141 charts. Overall, 23 patients showed a MGUS in their electrophoretic profile, though in 6 cases MGUS was detected at the baseline. Thereby, 17 cases (12.06% of the study population) developed MGUS during infliximab therapy. CONCLUSIONS: Serum protein electrophoresis test represents a useful tool to detect and monitor any potentially harmful condition that could occur during treatment with a biologic agent. Particularly, it could be crucial for the detection of MGUS, which does not affect clinical response, and it does not represent a criteria to withdraw the treatment. PMID- 26885781 TI - Lower Socioeconomic Status is Associated With Decreased Therapeutic Response to the Biologic Agents in Psoriasis Patients. AB - BACKGROUND: Lower socioeconomic status is associated with poorer overall health outcomes. However, few studies have examined the impact of socioeconomic status on psoriasis. OBJECTIVE: To examine the impact of individual socioeconomic status on systemic therapeutic outcomes amongst psoriasis patients. METHODS: The study analyzed 156 psoriasis patients treated at the Tufts Medical Center Department of Dermatology from 2008-2014. Individual socioeconomic status was inferred from neighborhood income, defined as the percentage of households with income below the federal poverty line (% below FPL) in the patient's census tract. The following outcomes were compared between socioeconomic groups: improvement in simple measure for assessing psoriasis activity (S-MAPA) score at 12 weeks, primary and secondary drug failure rates, and incidence of documented medication non-adherence. RESULTS: Those patients living in relatively poorer neighborhoods (% below FPL <= 10%) experienced a significantly decreased improvement in S-MAPA score at 12 weeks of biologic treatment when compared to those in relatively richer neighborhoods (% below FPL >10%), 23.2% vs. 45.5%, P=0.021. Patients living in poorer neighborhoods also had a significantly higher rate of primary drug failure when treated with biologics (34.7% vs. 18.4%, P=0.039) and were significantly more likely to have >= 1 documented instance of medication non adherence when treated with biologics (45.5% vs. 8.8%, P < 0.001). LIMITATIONS: Retrospective design, small sample size CONCLUSIONS: Our study offers preliminary data that suggests lower socioeconomic status may be associated with decreased clinical response to the biologic agents, presumably through decreased medication adherence. PMID- 26885780 TI - Zinc Pyrithione: A Topical Antimicrobial With Complex Pharmaceutics. AB - Zinc pyrithione (ZPT) is an active material that has been used for over 50 years to effectively treat dandruff and seborrheic dermatitis (D/SD). It has become the most common material for that purpose, its use has expanded to include other skin benefits such as skin hygiene. However, there is much about ZPT that is unappreciated. It is a rationally developed molecule that was modeled after the naturally occurring antimicrobial aspergillic acid. The molecular basis for its antifungal activity has been elucidated. The efficacy of ZPT originates from two attributes. First, it has a very broad antimicrobial spectrum of activity, including fungi, gram-positive and -negative bacteria. Second, the material has very low solubility, resulting in formulation and delivery as a particulate material, which has distinct performance advantages. The particles are deposited and retained on the target skin surfaces even when delivered from rinse-off products. These particles slowly release molecularly active material to interact with the surface fungal and bacteria cells to control their population, functioning as slow-release reservoirs to provide extended and persistent benefits. This particulate nature, though, results in complex pharmaceutics to realize the full efficacy benefits; it is common to see products with the same ZPT level having widely varying levels of clinical performance. Several product matrix-determined factors directly impact resultant benefits: ZPT must be retained on the skin surface achieving uniform spatial distribution laterally as well as within hair follicles (especially on scalp); ZPT must be maintained as a physically stable dispersion in product; ZPT must be maintained in a chemically active form as there are many chemical reactions that can occur that can harm ZPT bioactivity. The benefits achievable by employing ZPT require significant pharmaceutics expertise to realize the full benefits of this active material. PMID- 26885782 TI - DFD-01, a Novel Medium Potency Betamethasone Dipropionate 0.05% Emollient Spray, Demonstrates Similar Efficacy to Augmented Betamethasone Dipropionate 0.05% Lotion for the Treatment of Moderate Plaque Psoriasis. AB - BACKGROUND: A novel 0.05% betamethasone dipropionate emollient spray (DFD-01) was formulated to optimize penetration of steroid to the epidermal layers affected by psoriasis. OBJECTIVE: To compare the efficacy and safety of medium potency DFD-01 with super potent augmented betamethasone dipropionate 0.05% lotion (Diprolene) for the topical treatment of moderate plaque psoriasis. METHODS: Adults with moderate plaque psoriasis (Investigator Global Assessment [IGA]=3; 10-20% BSA) were randomized 2:1:1 to DFD-01, Diprolene, or Vehicle. Products were applied twice daily to affected areas for 14 days. Treatment success was defined as IGA=0 or 1 and >= 2-grade improvement from baseline. IGA and target lesion Total Sign Score (TSS; sum of erythema, scaling, and plaque elevation scores) were assessed at baseline and at days 4, 8, and 15. Adverse events (AEs) were recorded. RESULTS: 351 subjects with moderate psoriasis were randomized to DFD-01 (n=174), Diprolene (n=90), or Vehicle (n=87). Mean BSA was 13-14%. Treatment success was achieved in 19.0% DFD-01, 18.9% Diprolene, and 2.3% Vehicle (P<0.001 DFD-01 vs Vehicle) at day 15. Treatment success at day 8 was 10% DFD-01, 6.7% Diprolene, and 1.2% Vehicle (P=0.003 DFD-01 vs Vehicle). TSS was significantly reduced with DFD-01 compared with Vehicle at days 4, 8, and 15 (P <= 0.006) and compared with Diprolene at day 4 (P=0.010). DFD-01 relieved signs of erythema and scaling earlier than Diprolene or Vehicle, showing significant improvements on day 4 (P <= 0.048). All products were well tolerated. Significantly more burning/stinging was reported with Diprolene than DFD-01 (13.6% vs 4.1%, P=0.006). CONCLUSION: Medium potency DFD-01 was efficacious for the treatment of moderate psoriasis. DFD-01 demonstrated similar efficacy to super potent Diprolene lotion. Results at 4 and 8 days indicate that DFD-01 shows early improvement in some subjects. DFD 01 was well tolerated and had an excellent safety profile. PMID- 26885783 TI - Asthma and Atopic Dermatitis: A Review of Targeted Inhibition of Interleukin-4 and Interleukin-13 As Therapy for Atopic Disease. AB - Type 2 helper T cell (Th2)-mediated inflammation plays a critical role in the pathogenesis of allergic asthma and atopic dermatitis (AD). Recent research focusing on the suppression of the Th2 axis with targeted inhibitors in atopic disease is showing promising early results. In particular, the simultaneous blockage of interleukin (IL)-4 and IL-13 has successfully mitigated symptoms of allergic asthma and AD in preliminary clinical trials. Given the current therapeutic challenges of treating these chronic and severe diseases, this review brings to light new data demonstrating that agents targeting IL-4 and IL-13 are relatively safe and effective medications in blocking the inflammatory cascade responsible for allergic asthma and atopic dermatitis. PMID- 26885784 TI - Post Hoc Analyses of the Effect of Crisaborole Topical Ointment, 2% on Atopic Dermatitis: Associated Pruritus from Phase 1 and 2 Clinical Studies. AB - BACKGROUND: Two post hoc analyses assessed the antipruritic activity of crisaborole topical ointment, 2% (crisaborole; Anacor Pharmaceuticals, Inc., Palo Alto, CA), a first-in-class boron-based phosphodiesterase-4 inhibitor in development for treatment of mild to moderate atopic dermatitis (AD). METHODS: Two pooled analyses included data from 4 studies evaluating crisaborole in AD (study 1, phase 1b, systemic exposure, safety, and pharmacokinetics [PK] under maximal-use conditions in children and adolescents; study 2, phase 2a, safety and PK in adolescents; study 3, phase 2a, efficacy and safety in adults; study 4, phase 2, efficacy and safety in adolescents). Pooled data from studies 1 and 2 included whole body assessments; studies 3 and 4 included target lesion assessments. Pruritus severity was evaluated using a 4-point rating scale (0=none to 3=severe). Efficacy assessments included percent change from baseline in pruritus severity scores at days 8 (first pooled assessment), 15, 22, and 29 (whole body assessments) or days 15 (first pooled assessment), 22, and 29 (target lesions). Paired t-tests comparing change from baseline against zero were used to calculate P values. Categorical shifts in pruritus severity were also assessed (no to mild pruritus, 0-1.5; moderate to severe pruritus, 2-3). RESULTS: In the pooled analysis of studies 1 and 2 (N=57), the percent change from baseline in pruritus severity scores were 63.0% and 64.9% at days 8 and 29, respectively (P<0.001 for each). Similar results were observed in the pooled analysis of studies 3 and 4 (N=67). In both analyses, most patients had mild to no pruritus from the first time point assessed through the remainder of treatment. CONCLUSIONS: Treatment with crisaborole topical ointment, 2% resulted in statistically significant reductions in pruritus severity at the first time point evaluated in both analyses. These findings provide preliminary evidence of the antipruritic activity of crisaborole topical ointment, 2%. PMID- 26885785 TI - Randomized, Double-Blind, Split-Face Study to Compare the Irritation Potential of Two Topical Acne Formulations Over a 21-Day Treatment Period. AB - The use of fixed combinations in acne vulgaris (acne) is very common, however comparative clinical trial data are limited. Cutaneous tolerability can influence patient compliance, and concerns about skin irritation with topical acne treatments have lead to a number of comparative split-face studies. Recently, a new fixed combination product was introduced (clin 1.0%-BP 3.75% gel) that was shown to be effective in reducing both inflammatory and noninflammatory lesions in moderate to severe acne. Here, we assess the tolerability of clin 1.0%-BP 3.75% gel compared with adap 0.1%-BP 2.5% gel in healthy volunteers with no apparent facial redness or dryness over 21-days, using a split-face methodology. Especially over the first two weeks of treatment, clin 1.0%-BP 3.75% gel was more tolerable than adap 0.1%-BP 2.5% gel, with statistically significant differences in cumulative change from baseline starting as early as day 8 (dryness) and day 9 (erythema), and composite index on days 8-12 and 16. Transepidermal water loss was less with clin 1.0%-BP 3.75% gel, although the difference was not statistically significant. PMID- 26885786 TI - Understanding the Relationship Between Pruritus Severity and Work Productivity in Patients With Moderate-to-Severe Psoriasis: Sleep Problems Are a Mediating Factor. AB - BACKGROUND: Psoriasis is a debilitating skin disease associated with substantial pruritus, work impairment, and sleep disturbance. OBJECTIVE: This study evaluated associations between pruritus and work productivity, and the role of sleep problems as a possible mediator of the relationship between the two. METHODS AND MATERIALS: Data from a pruritus visual analog scale (Itch VAS), the Medical Outcomes Study Sleep Scale (MOS-SS), and the Work Productivity and Activity Impairment Questionnaire (WPAI) were collected in a phase 2 clinical trial in patients with psoriasis treated with ixekizumab or placebo. Mediating effects of sleep were tested in multiple regressions with pruritus severity (independent variable) and work productivity (dependent variable). Sobel tests evaluated the significance of sleep's effect. RESULTS: Several MOS-SS domains were significantly associated with the WPAI presenteeism, work productivity, and activity impairment scores, and decreased the effect of pruritus. Sobel tests indicated that the Sleep Problems Index I had a significant effect (P<.05) in mediating the relationship between pruritus and presenteeism, work productivity, and activity impairment. CONCLUSION: Sleep may mediate the role of pruritus on work productivity, but both factors appear to have independent negative effects on work. PMID- 26885787 TI - Use of Dapsone 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and Dapsone 5% Gel Combination Treatment. AB - BACKGROUND: Acne vulgaris is a common, chronic skin disease that requires long term therapy. Oral antibiotics are a mainstay of treatment, but extended use is associated with the development of bacterial resistance. Topical therapies are often combined with oral antibiotics to achieve an initial improvement, after which the oral agents may be discontinued and the topical therapy used as maintenance. OBJECTIVE: To assess the safety and efficacy of combination therapy with dapsone 5% gel with oral doxycycline hyclate 100mg, followed by monotherapy with dapsone 5% gel in improving and maintaining response in patients with moderate to severe acne. METHODS: In this open-label study, all patients applied dapsone 5% gel twice daily along with doxycycline hyclate 100mg once daily for 12 weeks. Subjects who achieved a qualifying improvement at week 12 continued to the second phase of the study in which they applied only dapsone 5% gel twice daily for maintenance therapy of 12 more weeks. Subjects were evaluated for safety and efficacy at weeks 4, 8, 12, 16, 20, and 24. RESULTS: All subjects (n=30) in the initial phase qualified to enter the maintenance phase. 82% of participants maintained their treatment response (Investigator's Global Assessment score) at week 24. The regimen was safe and well tolerated. CONCLUSIONS: The combination oral doxycycline hyclate 100 mg with topical dapsone 5% gel twice daily is an effective and well-tolerated regimen to treat moderate to severe acne vulgaris. After discontinuation of doxycycline, topical dapsone 5% gel is effective at maintaining a therapeutic response. These data suggest that topical dapsone 5% gel can be used effectively for long-term acne maintenance treatment without the risk of developing antibiotic resistance. PMID- 26885788 TI - The Efficacy and Safety of Topical Dapsone Gel, 5% for the Treatment of Acne Vulgaris in Adult Females With Skin of Color. AB - BACKGROUND: Topical dapsone gel, 5% is approved for treatment of acne vulgaris but has not been studied specifically in women with skin of color (SOC; Fitzpatrick skin types IV, V, or VI). OBJECTIVE: Evaluate safety and efficacy of dapsone gel, 5% applied topically twice daily for 12 weeks in women with SOC. METHODS: Females with SOC aged 18 years and older with facial acne participated in a multicenter, open-label, single-group, 12-week pilot study of twice-daily monotherapy with dapsone gel, 5%. The investigator-rated 5-point Global Acne Assessment Score (GAAS) was used to assess efficacy. The impact of acne on subjects was assessed using the validated Acne Symptom and Impact Scale (ASIS). RESULTS: The study enrolled and treated 68 women with SOC and facial acne. GAAS decreased significantly from baseline to week 12 (mean, -1.2 [95% CI, -1.4, 1.0]; P<.001), a 39.0% improvement. Overall, 42.9% of subjects were responders based on a GAAS of 0 or 1 at week 12. Subjects also experienced significant reductions in mean total lesions (52% decrease), inflammatory lesions (65%), and comedo counts (41%; all P<.001). Dapsone gel, 5% monotherapy was associated with significant improvement in subject-assessed acne signs (P<.001) and impact on quality of life (QOL; P<.001), based on ASIS. Dapsone gel, 5% used twice daily was well tolerated, with no treatment-related adverse events. The local dermal tolerability scores tended to remain stable or decrease from baseline to week 12. CONCLUSIONS: Monotherapy with dapsone gel, 5% administered twice daily was safe and effective for treatment of facial acne in women with SOC. Significant improvement in overall acne severity and both inflammatory lesions and comedones was observed. Further, study subjects reported considerable improvement in both acne signs and impact on QOL. PMID- 26885789 TI - Jasmonates and Tetrahydrojasmonic Acid: A Novel Class of Anti-Aging Molecules. AB - Jasmonates are plant-derived hormones from linoleic acid that were originally isolated from jasmine, and which are involved in plant stress regulation, wound repair and defense. They have been demonstrated through in vitro and in vivo studies to possess anti-neoplastic properties. Most recently, a novel jasmonate analog was developed, tetrahydrojasmonic acid (LR2412), which possesses favorable characteristics for cutaneous application and which induces improvements in epidermal hyaluronic acid and thickness. Clinical application of LR2412 to facial skin has been demonstrated to reduce the appearance of wrinkles and photoaging. In this issue, a clinical trial is published demonstrating the results of topical application of this agent for th cosmetic treatment of wrinkle appearance, poor texture and large pores. PMID- 26885790 TI - Clinical Assessment of a Novel Jasmonate Cosmeceutical, LR2412-Cx, for the Treatment of Skin Aging. AB - BACKGROUND: The jasmonates are a novel class of plant-derived anti-aging compounds. Among these, LR2412-Cx (tetrahydrojasmonic acid, Visionnaire) has been demonstrated to reduce photoaging and the appearance of wrinkles, as well as to upregulate collagens, hyaluronic acid and fibrillin. OBJECTIVE: To clinically study the cosmetic effects of a novel jasmonate complex LR2412-Cx in the treatment of visible skin aging. METHODS: LR2412-Cx was evaluated in a 15-subject open-label prospective clinical trial for the treatment of fine wrinkle appearance, texture, and pores. Subjects were evaluated by an investigator at baseline, day 1, day 3, and week 6 with the Alexiades comprehensive grading scale of skin aging, and introducing a novel pore-grading scale and subject quality of life assessments. RESULTS: The mean (SEM) at baseline and at week 6 following twice-daily application were: for the appearance of wrinkles 2.91 (0.12) and 2.70 (0.10); for texture 2.91 (0.10) and 2.55 (0.10); and for pores 3.29 (0.08) and 2.46 (0.09), respectively. The differences in all 3 categories at all follow-up intervals were statistically significant (P<.005). The percentage improvement in investigator-assessed grades relative to baseline at day 1, day 3, and week 6 were: 2.3%, 4.9%, and 7.4% for the appearance of wrinkles, 5.7%, 9.4%, and 12.4% for texture, and 14.2%, 21.6% and 25.2% for pores, respectively. No significant untoward effects were reported. CONCLUSION: Visionnaire LR2412-Cx is a novel jasmonate-containing compound that is safe and effective for the cosmetic treatment of fine wrinkle appearance, texture, and pores of the facial skin. PMID- 26885791 TI - Superior Efficacy of an Herbal-based Cosmeceutical Compared With Common Prescription and Cosmetic Antiaging Therapies. AB - INTRODUCTION: Research has shown that a disrupted stratum corneum permeability barrier coupled with chronic inflammation induce signs of extrinsic aging (photoaging). An novel herbal-based three product cosmeceutical regimen used to reverse these two anomalies that does not contain retinol, soy, niacinamide, tea, L-ascorbic acid or esters, hydroxy acids, tocopherol, or growth factors was tested in six human clinical trials to determine effectiveness and safety in reversing photoaging. MATERIALS AND METHODS: Six randomized split face, double blind, prospective, controlled clinical trials involving a total of 110 subjects compared a cosmeceutical blend of novel herbs in regimens consisting of one to three products to several common antiaging topical treatments. These comparative products include prescription tretinoin, physician strength idebenone, kinetin, polyhydroxy, lactic and glycolic acids in reversing signs of photoaging. RESULTS: The novel cosmeceutical blend regimen showed superior efficacy and safety in all six trials. DISCUSSION: These trials substantiate that herbs not used in common antiaging products effectively and safely mitigate and reverse photoaging signs and symptoms. The novel concept of treating photoaging and preventing its progression by repairing and optimizing the stratum corneum barrier, while reversing and inhibiting chronic cutaneous inflammation, has now been proven. PMID- 26885793 TI - Accelerated Onset of Action and Increased Tolerability in Treating Acne With a Fixed-Dose Combination Gel. AB - Nonadherence to topical acne therapies is a major contributing factor to poor treatment outcomes. Multiple contributing factors have been identified, including a lack of perceived efficacy and fear of side effects. A fixed-dose combination gel of adapalene/benzoyl peroxide gel, 0.1%/2.5% (A-BPO) is an efficacious and safe treatment for a range of acne severities in patients as young as 9 years old. A meta-analysis of 14 clinical studies involving A-BPO was conducted to assess the 4 week efficacy and overall tolerability of this treatment. Over 2,300 subjects were included in the analysis. Mean total, inflammatory, and non inflammatory lesion counts decreased at 4 weeks by 40.8%, 46.2%, and 37.5%, respectively. Worst post-baseline tolerability scores for stinging/burning, dryness, scaling, and erythema were none or mild for a majority of subjects. The result of this meta-analysis add to the body of literature supporting the use of A-BPO in a variety of acne patients and shows that A-BPO provides meaningful clinical results within 4 weeks and will be well-tolerated for a majority of patients. With a demonstrable quick onset of action and high tolerability, A-BPO may improve adherence, and ultimately treatment outcomes, by addressing factors that contribute to nonadherence. PMID- 26885794 TI - Oral Acyclovir in the Treatment of Verruca. AB - OBJECTIVE: To describe a case in which persistent plantar warts resolved after a ten-day treatment course of oral acyclovir prescribed for herpes zoster. CASE SUMMARY: A 49 year-old Caucasian female with non-significant past medical history presented to the podiatry clinic for treatment of verrucae. Debridement was performed and monochloroacetic acid was applied to affected areas seven times over seven months. The patient was diagnosed and treated for herpes zoster with acyclovir for ten days. Following acyclovir completion, only one verruca remained with complete resolution at the next follow-up podiatry visit. DISCUSSION AND CONCLUSION: Few previous trials have supported the use of acyclovir cream in treatment-resistant plantar warts. However, no case reports to date describe the efficacy of oral acyclovir in the treatment of verruca. While a causal relationship has not been solidified between verrucous lesion resolution and treatment with acyclovir, it can be inferred and warrants additional attention. PMID- 26885792 TI - Polypodium Leucotomos--An Overview of Basic Investigative Findings. AB - The use of Polypodium leucotomos, a species of fern, has been reported to be beneficial in the treatment of atopic dermatitis, vitiligo, and psoriasis, and for prevention of polymorphic light eruption, sunburn, and squamous cell carcinoma. We review the in vivo animal, in vitro human, and human clinical studies performed to help elucidate the actions of and biologic pathways affected by P. leucotomos. These results serve as the scientific rationale and basis for the protection and effectiveness afforded by P. leucotomos in cutaneous diseases. PMID- 26885795 TI - A Unique Case of Herpes Zoster Within One Week of Varicella Zoster Vaccination. AB - We report a unique case of herpes zoster that developed shortly after Varicella Zoster vaccination. PMID- 26885797 TI - Introduction to Advances in Tinea Pedis Management. PMID- 26885796 TI - Resident Rounds: Part III--Case Report: Crohn's Disease Presenting as Granulomatous Cheilitis. AB - Cutaneous Crohn's is a rare extra-intestinal manifestation of inflammatory bowel disease seen in a select group of patients, in which cutaneous lesions similar to those of the intestinal illness appear distant from the gastrointestinal tract. Oral findings may be found in up to 60% of patients with extra-intestinal Crohn's and may appear as the initial symptom underlying disease. We present a case of a 17-year-old male presenting with granulomatous chelitis of the lower lip who was unaware of the underlying diagnosis of Crohn's disease (CD). PMID- 26885798 TI - Advancements in Topical Antifungal Vehicles. AB - The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles. PMID- 26885799 TI - Mycological Considerations in the Topical Treatment of Superficial Fungal Infections. AB - Trichophyton rubrum remains the most common pathogenic dermatophyte in the United States, Europe, and industrialized Asia, although other species are predminant elsewhere. Candida albicans is the most common pathogenic yeast, with other species occasionally encountered. Just a few of the 14 described species of Malassezia cause pityriasis versicolor worldwide. FDA approval does not always accurately reflect the potential utility of any given topical antifungal agent. Azole, hydroxypyridone, and allylamine agents are beneficial in the management of dermatophytosis; however, the allylamines may lead to faster symptom resolution and a higher degree of sustained response. Although in actual clinical use the allylamines have all shown some activity against superficial cutaneous candidiasis and pityriasis versicolor, the azole agents remain drugs of choice. Ciclopirox is an excellent broad-spectrum antifungal agent. Optimal topical therapy for superficial fungal infections cannot yet be reliably based upon in vitro laboratory determination of sensitivity. Inherent antibacterial and anti inflammatory properties possessed by some antifungal agents may be exploited for clinical purposes. Candida species may be azole-insensitive due to efflux pumps or an altered target enzyme. So-called "antifungal resistance" of dermatophyets is actually due to poor patient adherence (either in dosing or treatment duration), or to reinfection. PMID- 26885800 TI - The Role of Naftifine HCl 2% Gel and Cream in Treating Moccasin Tinea Pedis. AB - In recent years, new topical antifungals have emerged for the treatment and management of tinea pedis, but all have been investigated and approved for the treatment of interdigital tinea pedis. Moccasin tinea pedis has not been recognized by governing bodies as a definable and treatable disease entity separate from interdigital tinea pedis at this time. Thus, creating randomized, controlled clinical trials to investigate moccasin tinea pedis is a challenge without an agreed upon definition of the disease state, treatment regimen, and treatment course. Considering systemic therapy issues and the lack of data from large trials demonstrating safety and efficacy in the topical management of this clinical presentation, an unmet need has been created for a topical antifungal agent that can treat moccasin tinea pedis. Naftifine 2% gel, an allylamine, was studied in a clinical trial that enrolled patients who had interdigital or both interdigital and moccasin-type tinea pedis. In the moccasin group, the primary efficacy endpoint of complete cure at week 2 (end of treatment) was 1.7% (gel) vs 0.9% (vehicle) and week 6 (four weeks post-treatment) was 19.2% (gel) vs 0.9% (vehicle). Naftifine 2% cream in combination with urea 39% also showed improvement in hyperkeratotic moccasin tinea pedis. PMID- 26885801 TI - Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C. AB - OBJECTIVE: Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. BACKGROUND: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. DESIGN/METHODS: A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). RESULTS: We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI <=0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and <=1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. CONCLUSIONS: Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy. PMID- 26885802 TI - Pharmacokinetics of Co-Formulated Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate After Switch From Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Healthy Subjects. AB - BACKGROUND: Elvitegravir (EVG), a HIV integrase inhibitor, is metabolized primarily by CYP3A, and secondarily by UGT1A1/3; Efavirenz (EFV), a HIV non nucleoside reverse transcriptase inhibitor, is metabolized by Cytochrome P450 (CYP) 2B6 and induces CYP3A and uridine diphosphate glucuronosyltransferase (UGT) with residual effects post discontinuation because of long T1/2 (40-55 hours). This study evaluated the pharmacokinetics after switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF). METHODS: Healthy subjects (n = 32 including n = 8 CYP2B6 poor metabolizers) received EVG/COBI/FTC/TDF (150/150/200/300 mg) on days 1-7, and after a washout, received EFV/FTC/TDF (600/200/300 mg) on days 15-28 and switched to EVG/COBI/FTC/TDF (150/150/200/300 mg) for 5 weeks (days 29-62). Pharmacokinetic assessments occurred on days 7, 28, 35, and 42; trough samples (Ctrough) were collected periodically until day 63. Safety was assessed throughout the study. RESULTS: Twenty-nine subjects completed with 3 adverse events leading to discontinuation; no grade >=3 adverse events were reported. Post-EFV/FTC/TDF, mean EVG area under concentration (AUCtau) was 37% and 29% lower and mean Ctrough ~3- and ~5-fold above IC95, respectively, on days 35 and 42, and 7-8-fold above IC95 by 5 weeks. COBI AUCtau returned to normal by day 42. EVG glucuronide, GS-9200, AUCtau was higher (46% and 32% on days 35 and 42, respectively) postswitch. CYP2B6 poor metabolizers displayed higher EFV AUCtau and Cmax (125% and 91%, respectively) versus non-poor metabolizers, and lower EVG and COBI exposures. EFV Ctrough was >IC90 (10 ng/mL) in all subjects postswitch. FTC and tenofovir (TFV) exposures were unaffected. CONCLUSIONS: After EFV/FTC/TDF to EVG/COBI/FTC/TDF switch, EVG and/or EFV exposures were in an active range. These findings support further evaluation of switching regimens in HIV-1 patients. PMID- 26885804 TI - HIV Testing, Care Referral, and Linkage to Care Intervals Affect Time to Engagement in Care for Newly Diagnosed HIV-Infected Adolescents in 15 Adolescent Medicine Clinics in the United States. AB - OBJECTIVE: To examine how the time from HIV testing to care referral and from referral to care linkage influenced time to care engagement for newly diagnosed HIV-infected adolescents. METHODS: We evaluated the Care Initiative, a care linkage and engagement program for HIV-infected adolescents in 15 US clinics. We analyzed client-level factors, provider type, and intervals from HIV testing to care referral and from referral to care linkage as predictors of care engagement. Engagement was defined as a second HIV-related medical visit within 16 weeks of initial HIV-related medical visit (linkage). RESULTS: At 32 months, 2143 youth had been referred. Of these, 866 were linked to care through the Care Initiative within 42 days and thus eligible for study inclusion. Of the linked youth, 90.8% were ultimately engaged in care. Time from HIV testing to referral (eg, <=7 days versus >365 days) was associated with engagement [adjusted odds ratio = 2.91; 95% confidence interval (CI): 1.43 to 5.94] and shorter time to engagement (adjusted hazard ratio = 1.41; 95% CI: 1.11 to 1.79). Individuals with shorter care referral to linkage intervals (eg, <=7 days versus 22-42 days) engaged in care faster (adjusted hazard ratio = 2.90; 95% CI: 2.34 to 3.60) and more successfully (adjusted odds ratio = 2.01; 95% CI: 1.04 to 3.89). CONCLUSIONS: These data address a critical piece of the care continuum and can offer suggestions of where and with whom to intervene to best achieve the care engagement goals outlined in the US National HIV/AIDS Strategy. These results may also inform programs and policies that set concrete milestones and strategies for optimal care linkage timing for newly diagnosed adolescents. PMID- 26885803 TI - Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression. AB - BACKGROUND: Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence. METHODS: The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced. RESULTS: The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence. CONCLUSIONS: Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women. PMID- 26885806 TI - Trends in Serosorting and the Association With HIV/STI Risk Over Time Among Men Who Have Sex With Men. AB - BACKGROUND: Serosorting among men who have sex with men (MSM) is common, but recent data to describe trends in serosorting are limited. How serosorting affects population-level trends in HIV and other sexually transmitted infection (STI) risk is largely unknown. METHODS: We collected data as part of routine care from MSM attending a sexually transmitted disease clinic (2002-2013) and a community-based HIV/sexually transmitted disease testing center (2004-2013) in Seattle, WA. MSM were asked about condom use with HIV-positive, HIV-negative, and unknown-status partners in the prior 12 months. We classified behaviors into 4 mutually exclusive categories: no anal intercourse (AI); consistent condom use (always used condoms for AI); serosorting [condom-less anal intercourse (CAI) only with HIV-concordant partners]; and nonconcordant CAI (CAI with HIV discordant/unknown-status partners; NCCAI). RESULTS: Behavioral data were complete for 49,912 clinic visits. Serosorting increased significantly among both HIV-positive and HIV-negative men over the study period. This increase in serosorting was concurrent with a decrease in NCCAI among HIV-negative MSM, but a decrease in consistent condom use among HIV-positive MSM. Adjusting for time since last negative HIV test, the risk of testing HIV positive during the study period decreased among MSM who reported NCCAI (7.1%-2.8%; P= 0.02), serosorting (2.4%-1.3%; P = 0.17), and no CAI (1.5%-0.7%; P = 0.01). Serosorting was associated with a 47% lower risk of testing HIV positive compared with NCCAI (adjusted prevalence ratio = 0.53; 95% confidence interval: 0.45 to 0.62). CONCLUSIONS: Between 2002 and 2013, serosorting increased and NCCAI decreased among Seattle MSM. These changes paralleled a decline in HIV test positivity among MSM. PMID- 26885805 TI - CD4/CD8 Ratio Predicts Peripheral Fat in HIV-Infected Population. PMID- 26885808 TI - Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021. AB - Accumulating evidence suggests that rates of low bone mass are greater in HIV infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss. PMID- 26885810 TI - High-Frequency Illegitimate Strand Transfers of Nascent DNA Fragments During Reverse Transcription Result in Defective Retrovirus Genomes. AB - BACKGROUND: Two strand transfers of nascent DNA fragments during reverse transcription are required for retrovirus replication. However, whether strand transfers occur at illegitimate sites and how this may affect retrovirus replication are not well understood. METHODS: The reverse transcription was carried out with reverse transcriptases (RTs) from HIV-1, HIV-2, and murine leukemia virus. The nascent complementary DNA fragments were directly cloned without polymerase chain reaction amplification. The sequences were compared with the template sequence to determine if new sequences contained mismatched sequences caused by illegitimate strand transfers. RESULTS: Among 1067 nascent reverse transcript sequences, most of them (72%) matched to the template sequences, although they randomly stopped across the RNA templates. The other 28% of them contained mismatched 3'-end sequences because of illegitimate strand transfers. Most of the illegitimate strand transfers (81%) were disassociated from RNA templates and realigned onto opposite complementary DNA strands. Up to 3 strand transfers were detected in a single sequence, whereas most of them (93%) contained 1 strand transfer. Because most of the illegitimate strand-transfer fragments were generated from templates at 2 opposite orientations, they resulted in defective viral genomes and could not be detected by previous methods. Further analysis showed that mutations at pause/disassociation sites resulted in significantly higher strand-transfer rates. Moreover, illegitimate strand transfer rates were significantly higher for HIV-2 RT (38.2%) and murine leukemia virus RT (44.6%) than for HIV-1 RT (5.1%). CONCLUSIONS: Illegitimate strand transfers frequently occur during reverse transcription and can result in a large portion of defective retrovirus genomes. PMID- 26885809 TI - Protective Role of BST2 Polymorphisms in Mother-to-Child Transmission of HIV-1 and Adult AIDS Progression. AB - Bone marrow stromal cell antigen-2 (BST-2)/Tetherin is a restriction factor that prevents Human immunodeficiency virus type 1 (HIV-1) release from infected cells and mediates pro-inflammatory cytokine production. This study investigated the risk conferred by single nucleotide polymorphisms (rs919266, rs9192677, and rs9576) at BST-2 coding gene (BST2) in HIV-1 mother-to-child transmission and in disease progression. Initially, 101 HIV-1+ pregnant women and 331 neonates exposed to HIV-1 from Zambia were enrolled. Additional BST2 single nucleotide polymorphism analyses were performed in 2 cohorts with acquired immunodeficiency syndrome (AIDS) progression: an adult Brazilian cohort (37 rapid, 30 chronic and 21 long-term non-progressors) and an Italian pediatric cohort (21 rapid and 67 slow progressors). The rs9576A allele was nominally associated with protection during breastfeeding (P = 0.019) and individuals carrying rs919266 GA showed slower progression to AIDS (P = 0.033). Despite the influence of rs919266 and rs9576 on BST2 expression being still undetermined, a preventive role by BST2 polymorphisms was found during HIV-1 infection. PMID- 26885811 TI - Comparison of Individual and Area Level Factors Between HIV-Infected Cisgender and Transgender Individuals in Florida (2006-2014). AB - This descriptive study compares individual- and area-level factors among HIV infected transgender and cisgender individuals in Florida using data from the Florida Department of Health HIV/AIDS surveillance system (2006-2014). Of those individuals diagnosed with HIV, 7 (0.01 %) identified as transgender males, 142 (0.3 %) as transgender females, 12,497 (25.7 %) as cisgender females, and 35,936 (74.0 %) as cisgender males. Transgender females resided in rural and urban areas, were disproportionately non-Hispanic black, and were more likely than cisgender women to be diagnosed with AIDS within 3 months of their HIV diagnosis. Results suggest HIV screening and outreach efforts should be enhanced for transgender women. PMID- 26885812 TI - Correlates of Combination Antiretroviral Adherence Among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years. AB - Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. The prevalence of optimal adherence was low (32 %) in this study. Males were more adherent than females (APR = 1.11, 95 % CI 1.02-1.21, P = 0.0127); persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60-0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75-0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73-0.92, P = 0.0008) were less adherent than those without any co morbidity; and residents of rural areas (APR = 0.90, 95 % CI 0.63-0.98, P = 0.0385) and small metropolitan areas (APR = 0.82, 95 % CI 0.72-0.94, P = 0.0032) were less adherent than residents of large metropolitan areas. There were no racial differences in optimal adherence. Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population. PMID- 26885813 TI - Information, Motivation, and Behavioral Skills of High-Risk Young Adults to Use the HIV Self-Test. AB - HIV self tests (HIVST) have the potential to increase testing among young adults. However, little is known about high-risk young adults' perception of the HIVST as a risk reduction tool and how they would use the HIVST in their everyday lives. Our study sought to examine these factors. Twenty-one ethnically diverse participants (ages 18-24) used the HIVST at our study site, completed surveys, and underwent an in-depth interview. Descriptive statistics were used to analyze the survey responses, and interview data were coded using constructs from the information-motivation-behavioral skills model. Information deficits included: how to use the HIVST and the "window period" for sero-conversion. Motivations supporting HIVST use included: not needing to visit the clinic, fast results, easy access, and use in non-monogamous relationships. Behavioral skills discussed included: coping with a positive test, handling partner violence after a positive test, and accessing HIV services. These findings can inform the use of the HIVST for improving HIV testing rates and reducing HIV risk behavior. PMID- 26885814 TI - Development and Validation of a Chromatographic Ultraviolet Method for the Simultaneous Quantification of Dolutegravir and Rilpivirine in Human Plasma. AB - BACKGROUND: We have developed and validated a high-performance liquid chromatographic method for the simultaneous quantification, in human plasma, of dolutegravir, a new human immunodeficiency virus (HIV) integrase inhibitor, and rilpivirine, a novel HIV nonnucleoside reverse transcriptase inhibitor. METHODS: An internal standard (quinoxaline) was added to plasma aliquots (500 MUL), and a simple solid-phase extraction procedure was applied. Chromatographic separation of the drugs and internal standard was achieved with a gradient of acetonitrile and acetate buffer, and with an analytical run time of 25 minutes using an XBridge C18 column. The column eluate was monitored at 260 nm for dolutegravir and the internal standard and at 305 nm for rilpivirine. RESULTS: The method was linear in the range of 20-8000 and 20-2000 ng/mL for dolutegravir and rilpivirine, respectively (mean r >= 0.993 on 10 replicates for both analytes). Mean intraday and interday precision and inaccuracy were <15% for both compounds. The mean recovery was 73% and 80% for dolutegravir and rilpivirine, respectively. CONCLUSIONS: The high-performance liquid chromatography-ultraviolet method we developed showed a good analytical performance required for therapeutic drug monitoring of antiretrovirals, leading to potential improvements in HIV-infected patient care and laboratory management. PMID- 26885819 TI - Amyloid PET Screening for Enrichment of Early-Stage Alzheimer Disease Clinical Trials: Experience in a Phase 1b Clinical Trial. AB - Amyloid positron emission tomography (PET) imaging is being investigated as a screening tool to identify amyloid-positive patients as an enrichment strategy for Alzheimer disease (AD) clinical trial enrollment. In a multicenter, phase 1b trial, patients meeting clinical criteria for prodromal or mild AD underwent florbetapir PET scanning at screening. PET, magnetic resonance imaging, and coregistered PET/magnetic resonance imaging scans were reviewed by 2 independent readers and binary visual readings tabulated. Semiquantitative values of cortical to whole cerebellar standard uptake value ratios were computed (threshold 1.10). Of 278 patients with an evaluable PET scan, 170 (61%) and 185 (67%) were amyloid positive by visual reading and quantitative analysis, respectively; 39% were excluded from the study due to an amyloid-negative scan based on visual readings. More ApoE epsilon4 carriers than noncarriers were amyloid-positive (80% vs. 43%). Comparison of visual readings with quantitative results identified 21 discordant cases (92% agreement). Interreader and intrareader agreements from visual readings were 98% and 100%, respectively. Amyloid PET imaging is an effective and feasible screening tool for enrollment of amyloid-positive patients with early stages of AD into clinical trials. PMID- 26885815 TI - Biodeterioration Risk Threatens the 3100 Year Old Staircase of Hallstatt (Austria): Possible Involvement of Halophilic Microorganisms. AB - BACKGROUND: The prosperity of Hallstatt (Salzkammergut region, Austria) is based on the richness of salt in the surrounding mountains and salt mining, which is documented as far back as 1500 years B.C. Substantial archaeological evidence of Bronze and Iron Age salt mining has been discovered, with a wooden staircase (1108 B.C.) being one of the most impressive and well preserved finds. However, after its discovery, fungal mycelia have been observed on the surface of the staircase, most probably due to airborne contamination after its find. OBJECTIVE: As a basis for the further preservation of this valuable object, the active micro flora was examined to investigate the presence of potentially biodegradative microorganisms. RESULTS: Most of the strains isolated from the staircase showed to be halotolerant and halophilic microorganisms, due to the saline environment of the mine. Results derived from culture-dependent assays revealed a high fungal diversity, including both halotolerant and halophilic fungi, the most dominant strains being members of the genus Phialosimplex (synonym: Aspergillus). Additionally, some typical cellulose degraders, namely Stachybotrys sp. and Cladosporium sp. were detected. Numerous bacterial strains were isolated and identified as members of 12 different genera, most of them being moderately halophilic species. The most dominant isolates affiliated with species of the genera Halovibrio and Marinococcus. Halophilic archaea were also isolated and identified as species of the genera Halococcus and Halorubrum. Molecular analyses complemented the cultivation assays, enabling the identification of some uncultivable archaea of the genera Halolamina, Haloplanus and Halobacterium. Results derived from fungi and bacteria supported those obtained by cultivation methods, exhibiting the same dominant members in the communities. CONCLUSION: The results clearly showed the presence of some cellulose degraders that may become active if the requirements for growth and the environmental conditions turn suitable; therefore, these microorganisms must be regarded as a threat to the wood. PMID- 26885820 TI - The Ratio of ADP- to TRAP-Induced Platelet Aggregation Quantifies P2Y12-Dependent Platelet Inhibition Independently of the Platelet Count. AB - OBJECTIVE: This study aimed to assess the association of clinical factors with P2Y12-dependent platelet inhibition as monitored by the ratio of ADP- to TRAP induced platelet aggregation and conventional ADP-induced aggregation, respectively. BACKGROUND: Controversial findings to identify and overcome high platelet reactivity (HPR) after coronary stent-implantation and to improve clinical outcome by tailored anti-platelet therapy exist. Monitoring anti platelet therapy ex vivo underlies several confounding parameters causing that ex vivo platelet aggregation might not reflect in vivo platelet inhibition. METHODS: In a single centre observational study, multiple electrode aggregometry was performed in whole blood of patients after recent coronary stent-implantation. Relative ADP-induced aggregation (r-ADP-agg) was defined as the ratio of ADP- to TRAP- induced aggregation reflecting the individual degree of P2Y12-mediated platelet reactivity. RESULTS: Platelet aggregation was assessed in 359 patients. Means (+/- SD) of TRAP-, ADP-induced aggregation and r-ADP-agg were 794 +/- 239 AU*min, 297 +/- 153 AU*min and 37 +/- 14%, respectively. While ADP- and TRAP induced platelet aggregation correlated significantly with platelet count (ADP: r = 0.302; p<0.001; TRAP: r = 0.509 p<0.001), r-ADP-agg values did not (r = -0.003; p = 0.960). These findings were unaltered in multivariate analyses adjusting for a range of factors potentially influencing platelet aggregation. The presence of an acute coronary syndrome and body weight were found to correlate with both ADP induced platelet aggregation and r-ADP-agg. CONCLUSION: The ratio of ADP- to TRAP induced platelet aggregation quantifies P2Y12-dependent platelet inhibition independently of the platelet count in contrast to conventional ADP-induced aggregation. Furthermore, r-ADP-agg was associated with the presence of an acute coronary syndrome and body weight as well as ADP-induced aggregation. Thus, the r ADP-agg is a more valid reflecting platelet aggregation and potentially prognosis after coronary stent-implantation in P2Y12-mediated HPR than conventional ADP induced platelet aggregation. PMID- 26885816 TI - Association between the Severity of Influenza A(H7N9) Virus Infections and Length of the Incubation Period. AB - BACKGROUND: In early 2013, a novel avian-origin influenza A(H7N9) virus emerged in China, and has caused sporadic human infections. The incubation period is the delay from infection until onset of symptoms, and varies from person to person. Few previous studies have examined whether the duration of the incubation period correlates with subsequent disease severity. METHODS AND FINDINGS: We analyzed data of period of exposure on 395 human cases of laboratory-confirmed influenza A(H7N9) virus infection in China in a Bayesian framework using a Weibull distribution. We found a longer incubation period for the 173 fatal cases with a mean of 3.7 days (95% credibility interval, CrI: 3.4-4.1), compared to a mean of 3.3 days (95% CrI: 2.9-3.6) for the 222 non-fatal cases, and the difference in means was marginally significant at 0.47 days (95% CrI: -0.04, 0.99). There was a statistically significant correlation between a longer incubation period and an increased risk of death after adjustment for age, sex, geographical location and underlying medical conditions (adjusted odds ratio 1.70 per day increase in incubation period; 95% credibility interval 1.47-1.97). CONCLUSIONS: We found a significant association between a longer incubation period and a greater risk of death among human H7N9 cases. The underlying biological mechanisms leading to this association deserve further exploration. PMID- 26885822 TI - Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion. AB - OBJECTIVE: To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO). SUBJECTS AND METHODS: We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean +/- standard deviation age was 69.1 +/- 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10 degrees was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined. RESULTS: One month after IVB, the BCVA improved significantly from 0.56 +/- 0.27 logMAR units to 0.32 +/- 0.28 logMAR units, and the CMT from 611.4 +/- 209.3 MUm to 258.7 +/- 64.0 MUm (P <0.05). The AT improved significantly from 17.9 +/- 5.3 dB to 21.2 +/- 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month. CONCLUSION: These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case. PMID- 26885823 TI - Narrowing the blockade field: development of an optimal postoperative analgesia regimen for total knee arthroplasty. PMID- 26885824 TI - Altered Cortico-Striatal Connectivity in Offspring of Schizophrenia Patients Relative to Offspring of Bipolar Patients and Controls. AB - Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence. PMID- 26885826 TI - Secondary SUNCT syndrome caused by dorsolateral medullary infarction. AB - Short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT) is a rare headache syndrome which belongs to trigeminal autonomic cephalalgias. Though the majority of SUNCT syndrome is idiopathic, more and more cases of secondary SUNCT syndrome have been reported recently. In this study, we present a case of symptomatic SUNCT syndrome caused by acute dorsolateral medullary infarction which was verified by brain MRI(magnetic resonance imaging). Up to now, there is not absolutely effective treatment for SUNCT syndrome. However, in our case, SUNCT was completely resolved after conventional treatment for cerebral infarction without specific drug intervention. PMID- 26885825 TI - Nigrostriatal dopaminergic depletion increases static orofacial allodynia. AB - BACKGROUND: This study investigated mesencephalic dopamine depletion effects on static mechanical allodynia (SMA) elicited by chronic constriction of the infraorbitary nerve (CCI-IoN). METHODS: Dopamine depletion (6-OHDA administration into the medial forebrain bundle) effects on CCI-IoN-induced SMA were explored using behavioral (nocifensive behavior score upon non-noxious stimuli using von Frey filament), pharmacological (bromocriptine injections) and immunohistochemical (PKCgamma and pERK1/2) techniques. RESULTS: The central dopamine depletion increased significantly the SMA score. Intraperitoneal and intracisternal injections of bromocriptine alleviated the allodynic behavior observed in both CCI-IoN and CCI-IoN + 6-OHDA animal groups. At the cellular level, dopamine depletion induced a significant increase in PKCgamma expression in the medullary dorsal horn (MDH) in rat with CCI-IoN + 6-OHDA when compared to sham animals (CCI-IoN only). Similarly, after static non-noxious stimuli, the expression of pain marker proteins pERK1/2 within the MDH revealed significantly a higher number of positive cells in CCI-IoN + 6-OHDA rats when compared to the CCI-IoN group. CONCLUSION: This study demonstrates that nigrostriatal dopamine depletion exacerbates the neuropathic pain resulting from CCI-IoN. This effect is probably due to an action through descending pain inhibitory systems which increased pain sensitization at the MDH level. It demonstrates also an analgesic effect elicited by D2R activation at the segmental level. PMID- 26885827 TI - Parental Acculturative Stressors and Adolescent Adjustment Through Interparental and Parent-Child Relationships in Chinese American Families. AB - Perpetual foreigner stereotype and bicultural management difficulty are two understudied acculturative stressors frequently experienced by Asian Americans. This study expanded the family stress model to examine how parental experiences of these two acculturative stressors relate to measures of adolescent adjustment (depressive symptoms, delinquent behaviors, and academic performance) during high school and emerging adulthood through interparental and parent-child relationship processes. Participants were 350 Chinese American adolescents (M age = 17.04, 58 % female) and their parents in Northern California. Path models showed that parental acculturative stressors positively related to parent-child conflict, either directly (for both mother-adolescent and father-adolescent dyads) or indirectly through interparental conflict (for mother-adolescent dyads only). Subsequently, both interparental and parent-child conflict positively related to a sense of alienation between parents and adolescents, which then related to more depressive symptoms, more delinquent behaviors, and lower academic performance in adolescents, for mother-adolescent and father-adolescent dyads. These effects persisted from high school to emerging adulthood. The results highlight the indirect effects of maternal and paternal acculturative stressors on adolescent adjustment through family processes involving interparental and parent-child relationships. PMID- 26885828 TI - Promotive and Corrosive Factors in African American Students' Math Beliefs and Achievement. AB - Framed by expectancy-value theory (which posits that beliefs about and the subjective valuation of a domain predict achievement and decision-making in that domain), this study examined the relationships among teacher differential treatment and relevant math instruction on African American students' self concept of math ability, math task value, and math achievement. These questions were examined by applying structural equation modeling to 618 African American youth (45.6 % female) followed from 7th to 11th grade in the Maryland Adolescent Development in Context Study. While controlling for gender and prior math achievement, relevant math instruction promoted and teacher differential treatment corroded students' math beliefs and achievement over time. Further, teacher discrimination undermined students' perceptions of their teachers, a mediating process under-examined in previous inquiry. These findings suggest policy and practice levers to narrow opportunity gaps, as well as foster math achievement and science, technology, engineering and math success. PMID- 26885829 TI - The Promotive and Protective Effects of Family Factors in the Context of Peer and Community Risks for Aggression. AB - A clearer understanding of the promotive factors that reduce adolescents' involvement in aggression and the protective factors that mitigate the influence of risk factors that emerge during adolescence is needed to inform prevention efforts. This study examined the promotive and protective influences of family factors on physical aggression using data collected from aggressive and socially influential adolescents (N = 537; 35 % female) at the beginning of sixth grade and at three subsequent waves across the following 3 years. Family characteristics (i.e., better family functioning, higher perceived parental support for nonviolence, and lower parental support for fighting) at the start of the sixth grade exerted promotive effects that reduced levels of aggression at subsequent waves. Some support was also found for protective influences. A foundation of good family functioning at the start of sixth grade buffered adolescents from the risks from delinquent peers, from the spring of sixth grade to the spring of seventh grade. Low parental support for fighting reduced risks associated with witnessing community violence, from the fall to the spring of sixth grade, but at low levels of risk only. These findings suggest that interventions targeting high-risk adolescents might benefit by enhancing both promotive and protective family factors. PMID- 26885830 TI - Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT). AB - Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis. PMID- 26885831 TI - Unrecognized Myocardial Infarction Assessed by Cardiac Magnetic Resonance Imaging -Prognostic Implications. AB - BACKGROUND: Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD. METHODS AND FINDINGS: In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade >=70%. In an age- and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery. CONCLUSIONS: The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR. TRIAL REGISTRATION: ClinicalTrials.gov NTC01257282. PMID- 26885832 TI - Mixtures of Two Bile Alcohol Sulfates Function as a Proximity Pheromone in Sea Lamprey. AB - Unique mixtures of pheromone components are commonly identified in insects, and have been shown to increase attractiveness towards conspecifics when reconstructed at the natural ratio released by the signaler. In previous field studies of pheromones that attract female sea lamprey (Petromyzon marinus, L.), putative components of the male-released mating pheromone included the newly described bile alcohol 3,12-diketo-4,6-petromyzonene-24-sulfate (DkPES) and the well characterized 3-keto petromyzonol sulfate (3kPZS). Here, we show chemical evidence that unequivocally confirms the elucidated structure of DkPES, electrophysiological evidence that each component is independently detected by the olfactory epithelium, and behavioral evidence that mature female sea lamprey prefer artificial nests activated with a mixture that reconstructs the male released component ratio of 30:1 (3kPZS:DkPES, molar:molar). In addition, we characterize search behavior (sinuosity of swim paths) of females approaching ratio treatment sources. These results suggest unique pheromone ratios may underlie reproductive isolating mechanisms in vertebrates, as well as provide utility in pheromone-integrated control of invasive sea lamprey in the Great Lakes. PMID- 26885834 TI - Treatment of Cutaneous Angioimmunoblastic T-Cell Lymphoma With Fractionated Carbon Dioxide Laser. PMID- 26885833 TI - Rapid Discovery and Functional Characterization of Terpene Synthases from Four Endophytic Xylariaceae. AB - Endophytic fungi are ubiquitous plant endosymbionts that establish complex and poorly understood relationships with their host organisms. Many endophytic fungi are known to produce a wide spectrum of volatile organic compounds (VOCs) with potential energy applications, which have been described as "mycodiesel". Many of these mycodiesel hydrocarbons are terpenes, a chemically diverse class of compounds produced by many plants, fungi, and bacteria. Due to their high energy densities, terpenes, such as pinene and bisabolene, are actively being investigated as potential "drop-in" biofuels for replacing diesel and aviation fuel. In this study, we rapidly discovered and characterized 26 terpene synthases (TPSs) derived from four endophytic fungi known to produce mycodiesel hydrocarbons. The TPS genes were expressed in an E. coli strain harboring a heterologous mevalonate pathway designed to enhance terpene production, and their product profiles were determined using Solid Phase Micro-Extraction (SPME) and GC MS. Out of the 26 TPS's profiled, 12 TPS's were functional, with the majority of them exhibiting both monoterpene and sesquiterpene synthase activity. PMID- 26885836 TI - Blunt Blade Subcision: An Evolution in the Treatment of Atrophic Acne Scars. AB - BACKGROUND: Subcision is the mainstay of atrophic acne scar treatment but the efficacy and safety of the procedure is controversial. OBJECTIVE: To improve the efficacy of the subcision procedure, a blunt subcision blade was designed and evaluated. METHODS: Eighteen patients with bilateral atrophic acne scars considered eligible for subcision were enrolled. Before subcision, a tumescent solution was injected subdermally to anesthetize the treatment area and aid the dissection of the dermal-subcutaneous tissue. Patients underwent treatment using the blunt subcision blade, a long metal blade with gradually narrowing edges, and a rounded blunt tip. Early postoperative complications, overall aesthetic improvement and persistent discoloration, or lumpiness were assessed 7 days after subcision and at a 6-month follow-up visit. RESULTS: Moderate to marked improvement of atrophic scars was observed in 15 cases (83.3%). Mild to moderate tenderness, periorbital ecchymoses, and swelling were reported by some patients, but resolved completely within 1 week after the procedure. No cases of persistent discoloration or lumpiness were observed at the final visit. CONCLUSION: The blunt blade subcision procedure is suggested as an effective method for the treatment of atrophic acne scars. PMID- 26885835 TI - Reply: "Repigmentation of Vitiligo Using Follicular Unit Extraction Technique" Dermatol Surg 2014;1425-1427. PMID- 26885837 TI - Reconstruction After Full-Thickness Loss of the Antihelix, Scapha, and Triangular Fossa. PMID- 26885839 TI - Exposure to industrial air pollutant emissions and lung function in children: Canadian Health Measures Survey, 2007 to 2011. AB - BACKGROUND: Long-term exposure to ambient air pollution has been associated with adverse effects on children's lung function. Few studies have examined lung function in relation to industrial emissions of air pollutants. DATA AND METHODS: This cross-sectional study was based on 2,833 respondents aged 6 to 18 for whom spirometry data were collected by the Canadian Health Measures Survey, 2007 to 2011. The weighted sum of industrial air emissions of nitrogen oxides (NOx) and fine particulate matter (PM2.5) within 25 km of the respondent's residence was derived using National Pollutant Release Inventory data. Multivariate linear regression was used to examine the relationship between NOx and PM2.5 emissions and forced vital capacity (FVC), the forced expiratory volume in 1 sec (FEV1), and the ratio of the two (FEV1/FVC). RESULTS: Industrial air emissions of NOx were not significantly associated with lung function among males or females. Emissions of PM2.5 were negatively associated with FEV1 and FEV1/FVC, but not FVC, among males. PM2.5 was not significantly related to lung function among females. INTERPRETATION: The associations that emerged between lung function and industrial emissions of PM2.5 among males were consistent with airway obstruction. Further research is warranted to investigate the gender differences observed in this study. PMID- 26885838 TI - Retroperitoneal Laparoscopic Management of Paraganglioma: A Single Institute Experience. AB - OBJECTIVES: To explore the feasibility and safety of retroperitoneal laparoscopic resection of paraganglioma (RLPG) in a large study population. METHODS: In a six year period, 49 patients with primary retroperitoneal paragangliomas (PG) underwent retroperitoneal laparoscopic surgery in a single center. Medical records were reviewed, and collected the following data, which were clinical characteristics, perioperative data (operative time, estimated blood loss, intraoperative hemodynamic changes, intraoperative and postoperative complications, and open conversions), and follow-up data (recurrence or distant metastases). RESULTS: All PGs were removed with negative tumor margin confirmed by postoperative histopathology. The operative time of RLPG was 101.59+/-31.12 minutes, and the estimated blood loss was 169.78+/-176.70ml. Intraoperative hypertensive and hypotensive episodes occurred in 25 cases and 27 cases, respectively. Two open conversions occurred. Two intraoperative complications occurred but were successfully managed endoscopically. Postoperative complications were minor and unremarkable. No local recurrence or distant metastasis were observed during the follow-up period. CONCLUSIONS: Our experience indicates the feasibility and safety of resection of PGs in a relatively large study population. PMID- 26885840 TI - Cadmium levels and sources of exposure among Canadian adults. AB - BACKGROUND: Cadmium is a heavy metal found naturally in the environment that has been associated with negative health outcomes. The present study examines levels of blood cadmium (BCd), urinary cadmium (UCd), and the main sources of cadmium exposure among Canadians aged 20 to 79. DATA AND METHODS: The data are from cycles 1 (2007 to 2009) and 2 (2009 to 2011) of the Canadian Health Measures Survey (CHMS), including measures of BCd and UCd, markers of smoking status (self reported and second-hand smoke exposure), and self-reported consumption of foods known to be high in cadmium. The relationship between sources of exposure and cadmium levels was examined descriptively. The magnitude of the contribution of different exposure sources was examined in regression models. RESULTS: Age and smoking status were the greatest contributors to BCd and UCd: older people and current smokers had the highest cadmium levels. Dietary exposure, while significant, was a modest contributor overall, but a more important source of cadmium among never-smokers. INTERPRETATION: Smoking was the greatest contributor to cadmium levels among Canadians aged 20 to 79. Dietary differences explained a small percentage of variation in cadmium levels. PMID- 26885841 TI - Effect of colchicine on serum lipid levels. PMID- 26885842 TI - Manner of death associated with autoerotic practice. PMID- 26885844 TI - Determination of the protonation state of the Asp dyad: conventional molecular dynamics versus thermodynamic integration. AB - The protonation state of the Asp dyad is important as it can reveal enzymatic mechanisms, and the information this provides can be used in the development of drugs for proteins such as memapsin 2 (BACE-1), HIV-1 protease, and rennin. Conventional molecular dynamics (MD) simulations have been successfully used to determine the preferred protonation state of the Asp dyad. In the present work, we demonstrate that the results obtained from conventional MD simulations can be greatly influenced by the particular force field applied or the values used for control parameters. In principle, free-energy changes between possible protonation states can be used to determine the protonation state. We show that protonation state prediction by the thermodynamic integration (TI) method is insensitive to force field version or to the cutoff for calculating nonbonded interactions (a control parameter). In the present study, the protonation state of the Asp dyad predicted by TI calculations was the same regardless of the force field and cutoff value applied. Contrary to the intuition that conventional MD is more efficient, our results clearly show that the TI method is actually more efficient and more reliable for determining the protonation state of the Asp dyad. PMID- 26885845 TI - Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers. AB - Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed. PMID- 26885846 TI - Bedside lung ultrasound in the evaluation of acute decompensated heart failure. AB - Dyspnea is a common presenting complaint in the emergency department (ED) and a leading cause of hospitalization in intensive care unit (ICU) and medical wards. Ultrasound (US) has traditionally been considered inadequate to explore the aerated lung. However, in the past 15 years LUS gained broader application, at least in part thanks to the interpretation of the artefacts generated by the interaction of US and lung structures/content. The total reflection of US beam occurring at the pleural level determines the artefactual image of the aerated lung: an homogenous 'foggy-like' picture under the pleural line. As the air content of the lungs decreases due to interstitial imbibition, deposition of collagen or presence of blood, vertical artefacts -arising from the pleural line and moving synchronously with the respiration- called B-lines appear. Multiple and bilateral B-lines identify the alveolar-interstitial syndrome (AIS). The most common cause of AIS is the wet lung: the more the congestion burden, the more the extent of the B-lines, which become confluent until the so-called white lung in case of pulmonary edema. Many studies showed a higher accuracy of LUS in diagnosing acute decompensated heart failure (ADHF) as compared to chest X-ray As recently shown, the integration of LUS to clinical assessment allow to differentiate cardiogenic dyspnea with sensitivity and specificity greater than 95 %. Moreover, LUS can easily detect pleural effusion -frequently present in ADHF-appearing as an anechoic area in the recumbent area of the thorax, delimited inferiorly by the diaphragmatic dome and superiorly by the aerated lung. PMID- 26885847 TI - Postoperative dyspnea mimicking pulmonary embolism as a result of regional nerve block. PMID- 26885843 TI - Characters, functions and clinical perspectives of long non-coding RNAs. AB - It is well established that most of the human genome and those of other mammals and plants are transcribed into RNA without protein-coding capacity, which we define as non-coding RNA. From siRNA to microRNA, whose functions and features have been well characterized, non-coding RNAs have been a popular topic in life science research over the last decade. Long non-coding RNAs (lncRNAs), however, as a novel class of transcripts, are distinguished from these other small RNAs. Recent studies have revealed a diverse population of lncRNAs with different sizes and functions across different species. These populations are expressed dynamically and act as important regulators in a variety of biological processes, especially in gene expression. Nevertheless, the functions and mechanisms of most lncRNAs remain unclear. In this review, we present recent progress in the identification of lncRNAs, their functions and molecular mechanisms, their roles in human diseases, their potential diagnostic and therapeutic applications as well as newer technologies for identifying deregulated lncRNAs in disease tissues. PMID- 26885848 TI - Residents values in a rational decision-making model: an interest in academics in emergency medicine. AB - Academic physicians train the next generation of doctors. It is important to understand the factors that lead residents to choose an academic career to continue to effectively recruit residents who will join the national medical faculty. A decision-making theory-driven, large scale assessment of this process has not been previously undertaken. To examine the factors that predict an Emergency resident's interest in pursuing an academic career at the conclusion of training. This study employs the ABEM Longitudinal Survey (n = 365). A logistic regression model was estimated using an interest in an academic career in residency as the dependent variable. Independent variables include gender, under represented minority status, survey cohort, number of dependent children, possession of an advanced degree, ongoing research, publications, and the appeal of science, independence, and clinical work in choosing EM. Logistic regression resulted in a statistically significant model (p < 0.001). Residents who chose EM due to the appeal of science, had peer-reviewed publications and ongoing research were more likely to be interested in an academic career at the end of residency (p < 0.05). An increased number of children (p < 0.05) was negatively associated with an interest in academics. Individual resident career interests, research productivity, and lifestyle can help predict an interest in pursuing an academic career. Recruitment and enrichment of residents who have similar values and behaviors should be considered in programs interested in generating more graduates who enter an academic career. PMID- 26885849 TI - Strength in Numbers: Visualizing CTL-Mediated Killing In Vivo. AB - Cytotoxic CD8+ T lymphocytes (CTLs) have long been believed to be extremely efficient killers. Forster and colleagues (Halle et al., 2016) used in vivo imaging to tell a different story, in which each CTL killed only 2-16 targets a day, and several CTLs per target were needed to get the job done. PMID- 26885850 TI - Bon EPOtit! S1P-Mediated EPO Signaling Whets a Macrophage's Appetite for Apoptotic Cells. AB - Phagocytes clear dying cells within an organism to prevent damaging inflammation and autoimmunity. In this issue of Immunity, Luo et al. (2016) describe how "find me" signals from apoptotic cells induce erythropoietin signaling within macrophages to prime them for efferocytosis. PMID- 26885852 TI - Costimulation Engages the Gear in Driving CARs. AB - In this issue of Immunity,Kawalekar et al. (2016) find that costimulation by a chimeric antigen receptor (CAR) can control T cell metabolism and balance the response toward long-lived memory or short-lived effector cells. The results provide a rationale of how to tune cancer immunotherapy more effectively in a hostile tumor environment. PMID- 26885851 TI - Fungi Take Control of Lymphocyte Recirculation. AB - Factors regulating leukocyte migration to neonatal lymph nodes are not sufficiently identified. In this issue of Immunity, Zhang et al. (2016) reveal that fungi drive emigration of gut DCs to lymph nodes, where these DCs instruct endothelial cell receptivity to leukocytes. PMID- 26885853 TI - ILC You Later: Early and Irreparable Loss of Innate Lymphocytes in HIV Infection. AB - Loss of IL-17-producing cells in the gut during HIV infection is linked to GI barrier damage. Kloverpris et al. (2016) find that circulating ILCs are lost early and irreversibly during HIV infection. Early ART administration protects against the ILC loss, and this might be clinically beneficial to HIV-infected individuals. PMID- 26885854 TI - TLRs of Our Fathers. AB - Two new studies published in The American Journal of Human Genetics (Dannemann et al., 2016; Deschamps et al., 2016) show that introgression of innate immune genes from Neandertals and Denisovans contributed to the modern genome of European and Asian, but not African, populations, and this might partly explain differences in susceptibility to immune-mediated diseases. PMID- 26885855 TI - Caspases Connect Cell-Death Signaling to Organismal Homeostasis. AB - Some forms of regulated cell death, such as apoptosis, are precipitated by the activation of cysteine proteases of the caspase family, including caspase 8, 9, and 3. Other caspases, such as caspase 1 and 4, are well known for their pro inflammatory functions but regulate cell death in a limited number of pathophysiological settings. Accumulating evidence suggests that the most conserved function of mammalian caspases is not to control cell death sensu stricto, but to regulate inflammatory and immune reactions to dying cells and infectious challenges. Here, we review the molecular and cellular mechanisms though which mammalian caspases connect cell-death signaling to the maintenance of organismal homeostasis. PMID- 26885856 TI - Glycogen Synthase Kinase 3 Inactivation Drives T-bet-Mediated Downregulation of Co-receptor PD-1 to Enhance CD8(+) Cytolytic T Cell Responses. AB - Despite the importance of the co-receptor PD-1 in T cell immunity, the upstream signaling pathway that regulates PD-1 expression has not been defined. Glycogen synthase kinase 3 (GSK-3, isoforms alpha and beta) is a serine-threonine kinase implicated in cellular processes. Here, we identified GSK-3 as a key upstream kinase that regulated PD-1 expression in CD8(+) T cells. GSK-3 siRNA downregulation, or inhibition by small molecules, blocked PD-1 expression, resulting in increased CD8(+) cytotoxic T lymphocyte (CTL) function. Mechanistically, GSK-3 inactivation increased Tbx21 transcription, promoting enhanced T-bet expression and subsequent suppression of Pdcd1 (encodes PD-1) transcription in CD8(+) CTLs. Injection of GSK-3 inhibitors in mice increased in vivo CD8(+) OT-I CTL function and the clearance of murine gamma-herpesvirus 68 and lymphocytic choriomeningitis clone 13 and reversed T cell exhaustion. Our findings identify GSK-3 as a regulator of PD-1 expression and demonstrate the applicability of GSK-3 inhibitors in the modulation of PD-1 in immunotherapy. PMID- 26885857 TI - CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation. AB - Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy. PMID- 26885858 TI - Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells. AB - Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs. PMID- 26885860 TI - Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. AB - Chimeric antigen receptors (CARs) redirect T cell cytotoxicity against cancer cells, providing a promising approach to cancer immunotherapy. Despite extensive clinical use, the attributes of CAR co-stimulatory domains that impact persistence and resistance to exhaustion of CAR-T cells remain largely undefined. Here, we report the influence of signaling domains of coreceptors CD28 and 4-1BB on the metabolic characteristics of human CAR T cells. Inclusion of 4-1BB in the CAR architecture promoted the outgrowth of CD8(+) central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies. PMID- 26885859 TI - A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling. AB - Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-gamma) receptor signaling. Mal-dependent IFN-gamma receptor (IFNGR) signaling led to mitogen-activated protein kinase (MAPK) p38 phosphorylation and autophagy. IFN-gamma signaling via Mal was required for phagosome maturation and killing of intracellular Mycobacterium tuberculosis (Mtb). The S180L polymorphism, and its murine equivalent S200L, reduced the affinity of Mal for the IFNGR, thereby compromising IFNGR signaling in macrophages and impairing responses to TB. Our findings highlight a role for Mal outside the TLR system and imply that genetic variation in TIRAP may be linked to other IFN-gamma-related diseases including autoimmunity and cancer. PMID- 26885863 TI - Case Series Investigating the Efficacy and Safety of Bilateral Fluocinolone Acetonide (ILUVIEN((r))) in Patients with Diabetic Macular Edema. AB - INTRODUCTION: Patients with diabetic macular edema (DME), a chronic, vision limiting condition, may be insufficiently responsive to standard-of-care anti vascular endothelial growth factor (VEGF) and/or laser therapies. One approved treatment for such patients is 0.2 MUg/day fluocinolone acetonide (FAc) sustained release implant; however, data are limited for treatment strategies in patients with bilateral chronic DME insufficiently responsive to standard-of-care therapies. METHODS: Six pseudophakic patients with bilateral, chronic DME previously treated with laser and anti-VEGF therapy (and intravitreal triamcinolone acetonide in 10 eyes) were retrospectively investigated for visual and anatomical outcomes, 6 months post-0.2 MUg/day FAc implant in both eyes. RESULTS: At baseline, the mean best corrected visual acuity (BCVA) was approximately 6/38 or 43 [standard deviation (SD) +/-17.4] Early Treatment Diabetic Retinopathy Study (ETDRS) letters; mean central retinal thickness (CRT) was 648 MUm (SD +/-160). Mean change in BCVA was +10 letters (SD +/-12.2 letters), with 4/12 eyes maintaining or achieving driving vision (>=70 letters) and 3/12 eyes having unchanged BCVA. CRT was reduced 6 months after 0.2 MUg/day FAc implant in 11/12 eyes. The mean intraocular pressure (IOP) was 16.1 mmHg [mean change of 1.1 mmHg (SD +/-3.6)]. CONCLUSION: In a real-world setting, 0.2 MUg/day FAc implant in both eyes was a feasible, effective choice for patients with severe bilateral DME, without notable increases in IOP. FUNDING: Publication charges were funded by Alimera Sciences Ltd. Medical writing assistance for this study was provided by QXV Communications and funded by Alimera Sciences Ltd. PMID- 26885861 TI - The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements. AB - Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells. PMID- 26885864 TI - Empathy and universal values explicated by the empathy-altruism hypothesis. AB - Research reports that empathy is on the decline in present-day society, together with an increasing trend in self-enhancing values. Based on the empathy-altruism hypothesis, we investigated whether these constructs are interlinked by analyzing the relationships between emotional and cognitive empathy and 10 universal values. In the first study, using a middle-aged U.S. sample, the results showed that empathy was strongly and positively related to altruistic values and negatively to self-enhancing values in a pattern that aligned with the empathy altruism hypothesis. In a second confirmation study, these findings were replicated and extended, while also controlling for the Big Five personality traits, to discount that empathy is only captured by basic personality. Only emotional empathy, not cognitive empathy, accounted for up to 18% additional variance in altruistic values, which further confirmed the emphasis on feelings, as postulated by the empathy-altruism hypothesis. PMID- 26885865 TI - True fenestration of the anterior communicating artery diagnosed by magnetic resonance angiography. AB - Variations of the anterior cerebral artery-anterior communicating artery (ACoA) complex are common. Most are duplicated or partially duplicated ACoAs that are confused with fenestration of the ACoA. We report here an extremely rare case of true fenestration of the ACoA diagnosed by magnetic resonance angiography. Tiny true fenestrations of the ACoA may be overlooked easily by MR angiography. Partial maximum-intensity-projection image and volume-rendering image are useful in identifying true fenestration of the ACoA. PMID- 26885862 TI - Analysis of the Rab GTPase Interactome in Dendritic Cells Reveals Anti-microbial Functions of the Rab32 Complex in Bacterial Containment. AB - Dendritic cells (DCs) orchestrate complex membrane trafficking through an interconnected transportation network linked together by Rab GTPases. Through a tandem affinity purification strategy and mass spectrometry, we depicted an interactomic landscape of major members of the mammalian Rab GTPase family. When complemented with imaging tools, this proteomic analysis provided a global view of intracellular membrane organization. Driven by this analysis, we investigated dynamic changes to the Rab32 subnetwork in DCs induced by L. monocytogenes infection and uncovered an essential role of this subnetwork in controlling the intracellular proliferation of L. monocytogenes. Mechanistically, Rab32 formed a persistent complex with two interacting proteins, PHB and PHB2, to encompass bacteria both during early phagosome formation and after L. monocytogenes escaped the original containment vacuole. Collectively, we have provided a functional compartmentalization overview and an organizational framework of intracellular Rab-mediated vesicle trafficking that can serve as a resource for future investigations. PMID- 26885867 TI - TLR3 deficiency increases voluntary alcohol consumption. AB - Toll-like receptors (TLRs) are innate immunity-related receptors. Many studies have indicated the involvement of TLRs in neurophysiology and neuropathology. One study showed that TLR3 regulates hippocampal memory and is highly expressed in the mesolimbic dopamine system, suggesting that TLR3 signaling may regulate alcohol consumption. The present study assessed the potential role of TLR3 in alcohol intake pattern. We used adult BalbC wild-type mice and TLR3 knockout mice and tested two-bottle alcohol preference over 15 days and one-bottle 2 or 4 h drinking in the dark over 4 consecutive days. The 10% alcohol consumption rate of TLR3 knockout mice increased on the 24 h free-choice test. Our findings support a potential regulatory role of TLR3 in alcohol consumption. PMID- 26885868 TI - The involvement of sirtuins during optic nerve injury of rats. AB - Sirtuins, comprised of seven members, protect cells from injury, possibly through different roles. In this study, we used two young rat optic nerve injury models to analyze the changes in Sirts 1-7 at different time points to better understand the role of sirtuins during optic nerve injury. Twelve-week-old adult male F344 rats (total n=42) were divided randomly into two groups. One group was subjected to optic nerve cut (ON-cut) and the other group was subjected to a peripheral nerve-optic nerve graft (PN-ON graft) on the left eye. At 1 and 3 days and 1, 2, and 4 weeks, rats were euthanized and retinas of both eyes were removed. Total RNA was extracted and first-strand cDNA was synthesized. Sirts 1-7 and housekeeping beta-actin quantitative real-time PCR were performed. The quantitative real-time PCR profile showed that sirtuin mRNAs in both groups increased following optic nerve injury with and without peripheral nerve grafting. Sirt1 mRNA increased rapidly, reaching its peak at 3 days after surgery. Sirts 2-7 showed an increasing trend and remained high through 4 weeks after surgery. Sirts 4 and 6 were the only Sirts that increased in number in the PN-graft group at 4 weeks after surgery, where neuronal survival should be higher. Our data indicate that Sirt1 and Sirts 2-7 may play different or complementary roles in optic nerve injury and that Sirts 4 and 6 may play a greater role than the remaining Sirts in axon regeneration. PMID- 26885866 TI - The role of leptin in central nervous system diseases. AB - Leptin is a peptide hormone produced by adipose tissue and acts in brain centers to control critical physiological functions. Leptin receptors are especially abundant in the hypothalamus and trigger specific neuronal subpopulations, and activate several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway. Although most studies focus on its role in energy intake and expenditure, leptin also plays a critical role in many central nervous system diseases. PMID- 26885869 TI - Special considerations for the treatment of chronic kidney disease in the elderly. AB - Chronic kidney disease (CKD) is common in older adults, and its burden is expected to increase in older populations. Even if the knowledge on the approach to older patient with CKD is still evolving, current guidelines for pharmacological management of CKD does not include specific recommendations for older patients. Additionally, decision-making on renal replacement therapy (RRT) for older patients is far from being evidence-based, and despite the improvement in dialysis outcomes, RRT may cause more harm than benefit compared with conservative care when prognostic stratification is not carefully assessed. The use of comprehensive geriatric assessment tools could help clinicians in applying a more informed decision-making. Finally, physical exercise and rehabilitation interventions also represents a promising therapeutic strategy. PMID- 26885870 TI - New Sunscreens and the Precautionary Principle. PMID- 26885871 TI - Teamwork and Collaboration for Prevention of Surgical Site Infections. AB - BACKGROUND: The surgeon has been regarded as the "captain of the ship" in the operating room (OR) for many years, but cannot accomplish successful operative intervention without the rest of the team. METHODS: Review of the pertinent English-language literature. RESULTS: Many reports demonstrate very different impressions of teamwork and communication in the OR held by different members of the surgical team. Objective measures of teamwork and communication demonstrate a reduction in complications including surgical site infections with improved teamwork and communication, with fewer distractions such as noise, and with effective use of checklists. CONCLUSION: Efforts to improve teamwork and communication and promote the effective use of checklists promote patient safety and improved outcomes for patients with reduction in surgical site infections. PMID- 26885872 TI - Ultrasound-Guided Transversus Abdominis Plane Block for Analgesia in Laparoscopic Cholecystectomy: A Systematic Review and Meta-Analysis. AB - OBJECTIVES: To evaluate the analgesic efficacy of ultrasound-guided transversus abdominis plane (TAP) block for patients undergoing laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: A systematic literature search was conducted to identify randomized controlled trials that compared ultrasound-guided TAP block with control for analgesia in adult patients undergoing LC. The original data were pooled for the meta-analysis using Review Manager 5. The main outcomes included postoperative pain intensity, opioid consumption, and adverse events. Out of a total of 77 trials, 7 were included. RESULTS: Compared with control, ultrasound-guided TAP block reduced the following: (1) postoperative pain intensity (visual analog scale: 0-10) both at rest and on movement at 0, 2, 4, 8, and 24 h (at rest: mean difference, MD(0 h) = -2.19, 95% confidence interval, CI: -3.46 to -0.91, p = 0.0008; on movement: MD(0 h) = -2.67, 95% CI: -3.86 to -1.48, p < 0.0001); (2) intraoperative fentanyl consumption (MD = -27.85 ug, 95% CI: 44.91 to -10.79, p = 0.001), and (3) morphine consumption in the recovery room (MD = -1.57 mg, 95% CI: -3.0 to -0.14, p = 0.03) and 0-24 h postoperatively. Fewer patients required analgesics in the recovery room when receiving TAP blocks (risk ratio, RR = 0.35, 95% CI: 0.20 to 0.62, p = 0.0003). TAP blocks also reduced postoperative nausea and vomiting (RR = 0.48, 95% CI: 0.28 to 0.81, p = 0.006). None of the studies reported symptoms of local anesthetic toxicity. CONCLUSIONS: In this study, the ultrasound-guided TAP block was an effective strategy for analgesia in patients undergoing LC. PMID- 26885874 TI - Interlayer Interactions in van der Waals Heterostructures: Electron and Phonon Properties. AB - Artificial van der Waals heterostructures constitute an emerging field that promises to design systems with properties on demand. Stacking patterns and the utilization of different types of chemically inert layers can deliver novel materials and devices. Despite the relatively weak van der Waals interaction, which does not affect the electronic properties around the Fermi level, our first principles calculations show significant changes in the higher conduction and deeper valence regions in the considered graphene/silicene, graphene/MoS2, and silicene/MoS2 systems. Such changes are linked to strong out-of-plane hybridization effects and van der Waals interactions. We also find that the interface coupling significantly affects the vibrational properties of the heterostructures when compared to the individual constituents. Specifically, the van der Waals coupling is found to be a major factor for the stability of the system. The emergence of shear and breathing modes, as well as the transformation of flexural modes, are also found. PMID- 26885875 TI - Annual Survey of Horsehair Worm Cysts in Northern Taiwan, with Notes on a Single Seasonal Infection Peak in Chironomid Larvae (Diptera: Chironomidae). AB - The life cycle of the freshwater horsehair worm typically includes a free-living phase (adult, egg, larva) and a multiple-host parasitic phase (aquatic paratenic host, terrestrial definitive host). Such a life cycle involving water and land can improve energy flow in riparian ecosystems; however, its temporal dynamics in nature have rarely been investigated. This study examined seasonal infection with cysts in larval Chironominae (Diptera: Chironomidae) in northern Taiwan. In the larval chironomids, cysts of 3 horsehair worm species were identified. The cysts of the dominant species were morphologically similar to those of Chordodes formosanus. Infection with these cysts increased suddenly and peaked 2 mo after the reproductive season of the adult horsehair worms. Although adult C. formosanus emerged several times in a year, only 1 distinct infection peak was detected in September in the chironomid larvae. Compared with the subfamily Chironominae, samples from the subfamilies Tanypodinae and Orthocladiinae were less parasitized. This indicates that the feeding behavior of the chironomid host likely affects horsehair worm cyst infections; however, bioconcentration in predatory chironomids was not detected. PMID- 26885873 TI - Canakinumab in recessive dystrophic epidermolysis bullosa: a novel unexpected weapon for non-healing wounds? PMID- 26885876 TI - Picosecond Pulse Radiolysis of Highly Concentrated Carbonate Solutions. AB - Highly concentrated potassium carbonate aqueous solutions are studied by picosecond pulse radiolysis with the purpose of exploring the formation processes of carbonate radical CO3(*-). The transient absorption band of solvated electron produced by ionizing is markedly shifted from 715 to 600 nm when the solute concentration of K2CO3 is 5 mol L(-1). This spectral shift is even more important than that observed for the solvated electron in 10 mol L(-1) KOH solutions. The broad absorption band of solvated electron in K2CO3 solutions overlaps with that of carbonate radical CO3(*-) formed at ultrashort time. Nitrate ion is used to scavenge the solvated electron and to observe the contribution of carbonate radical CO3(*-). The analysis of the amplitude and the kinetics of carbonate radical formation in highly concentrated solutions shows that CO3(*-) is formed within the electron pulse (7 ps) by two parallel mechanisms: a direct effect on the solute and the oxidation of the solute by water radical hole H2O(*+). These two mechanisms are followed by an additional one, by reaction between the solute and OH(*) radical especially in lower concentration. The radiolytic yield of each process is discussed. PMID- 26885877 TI - Behavioral Screening and Intervention for Improving Lower-Extremity Arthroplasty Outcomes and Controlling Costs. PMID- 26885878 TI - Role of Calcium in Secondary Structure Stabilization during Maturation of Nitrous Oxide Reductase. AB - The copper enzyme nitrous oxide reductase catalyzes the two-electron reduction of nitrous oxide N2O to dinitrogen N2. Its maturation largely occurs in the periplasm and includes the insertion of at least one Ca2+ ion per monomer. Here we have investigated the role of this structural cation in recombinantly produced apo-N2OR from Shewanella denitrificans and have determined the three-dimensional structure of the protein by X-ray crystallography. In the absence of Ca2+, substantial parts of the enzyme surrounding the binding sites for the copper ions show structural disorder. Reconstitution of the binuclear CuA site was possible in vitro but required the presence of Ca2+ ions for a stable insertion of the center. In contrast, an excess of Ca2+ prevented copper insertion, and the structural analysis of the Ca2+apo form revealed that the cation is sufficient to structure the disordered regions of the protein even in the absence of Cu ions, indicating that the geometry of the two noncanonical copper centers is largely predetermined by the protein structure. PMID- 26885879 TI - Improving the Description of the Optical Properties of Carotenoids by Tuning the Long-Range Corrected Functionals. AB - In this work we use gap-fitting procedure to tune the long-range corrected functionals and accurately investigate the electronic and optical properties of the five main molecules composing Buriti oil (extracted from Mauritia flexuosa L.) in the framework of density functional theory (DFT) and time-dependent (TD) DFT. The characteristic length (1/omega) was observed to be entirely system dependent, though we concluded that its determination is of fundamental importance to rescue geometrical, electronic, and optical properties with accuracy. We demonstrate that our approach of tuning characteristic length for each system resulted in an absorbance spectra in better experimental agreement when compared to the traditional methodology. Therefore, this study indicates that the tuning of the range-separation parameter is crucial to improve the description of the optical properties of conjugated molecules when TDDFT is used. For example, the wavelength of maximum absorption, lambdamax, for the phytofluene, obtained using B3LYP, is 381 nm, while using the gap-fitting procedure for the tuned-LC-BLYP the estimated lambdamax changed to 358 nm. The latter estimate is in better agreement with the experimental value of 350 nm. PMID- 26885880 TI - Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children. AB - CONTEXT: Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. OBJECTIVE: The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9-13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. DESIGN: Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. RESULTS: Baseline serum 25(OH)D was inversely associated with insulin (r = -0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = -0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P < .003) over the 12 weeks, despite vitamin D dose-dependent increases in serum 25(OH)D. CONCLUSIONS: Despite significant baseline inverse relationships between serum 25(OH)D and measures of insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children. PMID- 26885882 TI - Low Endogenous Secretory Receptor for Advanced Glycation End-Products Levels Are Associated With Inflammation and Carotid Atherosclerosis in Prediabetes. AB - CONTEXT: Prediabetes is associated with atherosclerotic vascular damage. OBJECTIVE: We investigated the correlation of endogenous secretory receptor for advanced glycation end-products (esRAGE), total soluble RAGE (sRAGE) and markers of inflammation, with early cardiovascular disease in subjects with prediabetes. We particularly focused on individuals with prediabetes identified only by glycated hemoglobin A1c (HbA1c) (5.7-6.4%) who had normal fasting glucose and were normotolerant after oral glucose tolerance test. DESIGN: This was a cross sectional study. SETTING: The study was conducted in the Department of Clinical and Molecular Medicine, University of Catania, Italy. MAIN OUTCOME MEASURE: sRAGE, esRAGE, carboxymethyl-lysine, S100A12, HbA1c, fasting glycemia, oral glucose tolerance test, pulse wave velocity, and intima-media thickness were evaluated in subjects with prediabetes. PATIENTS: Three hundred eighty subjects without previous history of diabetes were stratified into three groups: controls (n = 99), prediabetes (n = 220), and new-onset type 2 diabetes (n = 61). RESULTS: Subjects with prediabetes exhibited the following: lower esRAGE (0.29 +/- 0.18 vs 0.45 +/- 0.26 ng/mL; P < .05) and higher S100A12 levels than controls. RT-PCR analysis in mononuclear cells revealed that the mRNA expression level of the esRAGE splice variant progressively decreased in patients with prediabetes and type 2 diabetes with respect to controls. No difference was observed in sRAGE and carboxymethyl-lysine plasma levels between the groups. After multiple regression analyses, only age, HbA1c, and hs-CRP were independently associated with esRAGE levels. Age, HbA1c, and esRAGE were the major determinants of intima-media thickness, whereas S100A12 and systolic blood pressure were the major determinants of pulse wave velocity. When we analyzed the subjects with HbA1c prediabetes (normal fasting glucose/normotolerant and HbA1c 5.7-6.4%), esRAGE and inflammatory markers plasma levels still remained significantly different in respect to controls. CONCLUSIONS: Subjects with HbA1c prediabetes exhibited significantly reduced esRAGE levels and increased levels of markers of inflammation. These alterations are associated with early markers of cardiovascular disease. PMID- 26885883 TI - Pyruvate Improved Insulin Secretion Status in a Mitochondrial Diabetes Mellitus Patient. AB - CONTEXT: Mitochondrial diabetes is a rare form of diabetes mellitus accounting for up to 1% of all diabetes. Pyruvate therapy has been reported to be a potential therapeutic choice for patients with mitochondrial diseases. CASE DESCRIPTION: Water-based sodium pyruvate solutions (0.5 g/kg, thrice daily) were administrated orally to a 32-year-old Japanese male with mitochondrial diabetes and myopathy caused by m.14709T>C mutation. At the age of 20 years, he was diagnosed with diabetes mellitus and started insulin therapy. He tested negative for islet cell and glutamic decarboxylase antibodies. To evaluate favorable therapeutic improvements, we measured the lactate and pyruvate levels in plasma and cerebrospinal fluid; urinary C-peptide, glycated hemoglobin, and glycoalbumin levels; and total daily insulin dose (TDD). The patient experienced no side effects such as diarrhea because of pyruvate therapy. His urinary C-peptide level improved from 4.3 to 17.2 MUg/d after 1 day and to 30.2 MUg/d after 6 months of pyruvate therapy. TDD decreased from 33 to 20 U/d after 6 months of pyruvate therapy, but the lactate levels of plasma and cerebrospinal fluid and the lactate/pyruvate ratio did not change. CONCLUSIONS: Sodium pyruvate improved insulin secretion and resulted in decreased TDD in a patient with mitochondrial diabetes. Pyruvate therapy may be a potential therapeutic choice for patients with mitochondrial diabetes. Clinical trials involving a larger number of patients and long-term evaluation of the therapy are necessary to clarify the efficacy of pyruvate therapy. PMID- 26885881 TI - Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis. AB - CONTEXT: Dehydroepiandrosterone (DHEA) and T hormones are advertised as antiaging, antiobesity products. However, the evidence that these hormones have beneficial effects on adipose tissue metabolism is limited. OBJECTIVE: The objective of the study was to determine the effect of DHEA and T supplementation on systemic lipolysis during a mixed-meal tolerance test (MMTT) and an iv glucose tolerance test (IVGTT). DESIGN: This was a 2-year randomized, double-blind, placebo-controlled trial. SETTING: The study was conducted at a general clinical research center. PARTICIPANTS: Sixty elderly women with low DHEA concentrations and 92 elderly men with low DHEA and bioavailable T concentrations participated in the study. INTERVENTIONS: Elderly women received 50 mg DHEA (n = 30) or placebo (n = 30). Elderly men received 75 mg DHEA (n = 30), 5 mg T (n = 30), or placebo (n = 32). MAIN OUTCOME MEASURES: In vivo measures of systemic lipolysis (palmitate rate of appearance) during a MMTT or IVGTT. RESULTS: At baseline there was no difference in insulin suppression of lipolysis measured during MMTT and IVGTT between the treatment groups and placebo. For both sexes, a univariate analysis showed no difference in changes in systemic lipolysis during the MMTT or IVGTT in the DHEA group and T group when compared with placebo. There was no change in the results after adjusting for the resting energy expenditure, except for a small, but significant (P = .03) lowering of MMTT nadir palmitate rate of appearance in women who received DHEA. CONCLUSION: In elderly individuals with concentrations of DHEA (men and women) or T (men) below the normal range for young adults, supplementation of these hormones has no effect on insulin suppression of systemic lipolysis. PMID- 26885884 TI - Organohalide Lead Perovskites for Photovoltaic Applications. AB - Perovskite solar cells have recently exhibited a significant leap in efficiency due to their broad absorption, high optical absorption coefficient, very low exciton binding energy, long carrier diffusion lengths, efficient charge collection, and very high open-circuit potential, similar to that of III-IV semiconductors. Unlike silicon solar cells, perovskite solar cells can be developed from a variety of low-temperature solutions processed from inexpensive raw materials. When the perovskite absorber film formation is optimized using solvent engineering, a power conversion efficiency of over 21% has been demonstrated, highlighting the unique photovoltaic properties of perovskite materials. Here, we review the current progress in perovskite solar cells and charge transport materials. We highlight crucial challenges and provide a summary and prospects. PMID- 26885885 TI - Perceptions and correlates of pubic hair removal and grooming among college-aged women: a mixed methods approach. AB - Background Although much is known about behavioural indicators of pubic hair removal, current research lacks deeper cognitive reasoning and understanding through utilising quantitative and qualitative methodologies. The purpose of this study was to: (1) describe and understand pubic hair removal behaviours using a quantitative survey; and (2) examine the relationship between pubic hair removal, sexual behaviours and genital self-image using in-depth interviews. METHODS: Data were collected from women aged 18-24 years living in the United States. Overall, 663 participants completed an online survey and 53 completed in-depth interviews. Questions asked related to pubic hair removal and sexual history. RESULTS: Participants removed hair for hygiene, comfort and sensation purposes, which was a personal decision influenced by family, friends and the media. Race, pubic hair removal initiation age, genital image and sexual behaviours were significantly related to pubic hair removal. CONCLUSIONS: Data from this study prove that further education regarding safe pubic hair removal methods is needed, especially for those who initiate pubic hair removal and sexual behaviours concurrently. PMID- 26885886 TI - New Alkaloids from Green Vegetable Soybeans and Their Inhibitory Activities on the Proliferation of Concanavalin A-Activated Lymphocytes. AB - A comprehensive phytochemical study of the chemical constituents of green vegetable soybeans resulted in the isolation of two new alkaloids, soyalkaloid A, 1, and isoginsenine, 2, together with four known ones, ginsenine, 3, (1S,3S)-1 methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 4, (1R,3S)-1-methyl 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, 5, and indole-3-carboxylic acid, 6. The structures of compounds 1-6 were elucidated on the basis of spectroscopic and chemical analyses. All of the alkaloids were isolated from soybeans for the first time, and compound 1 was a new indole-type alkaloid with a novel carbocyclic skeleton. Their inhibitory activities on the proliferation of concanalin A-activated lymphocytes were assessed by CCK8 assay. PMID- 26885889 TI - Highly water-soluble mast cell stabiliser-encapsulated solid lipid nanoparticles with enhanced oral bioavailability. AB - Cromolyn sodium (CS), a mast cell stabiliser, is widely employed for the prevention and treatment of allergic conditions. However, high hydrophilicity and poor oral permeability hinder its oral clinical translation. Here, solid lipid nanoparticles (SLNs) have been developed for the purpose of oral bioavailability enhancement. The CS-SLNs were engineered by double emulsification method (W1/O/W2) and optimised by using Box-Behnken experimental design. The surface and solid-state characterisations revealed the presence of CS in an amorphous form without any interactions inside the spherical-shaped SLNs. The in-vitro release study showed an extended release up to 24 hr by diffusion controlled process. Ex vivo and in-vivo intestinal permeation study showed ~2.96-fold increase in permeability of CS by presentation as SLNs (p < 0.05). Further, in-vivo pharmacokinetic study exhibited ~2.86-fold enhancements in oral bioavailability of CS by encapsulating inside SLNs, which clearly indicate that SLNs can serve as the potential therapeutic carrier system for oral delivery of CS. PMID- 26885890 TI - Influenza infection in human host: challenges in making a better influenza vaccine. AB - Influenza is a ubiquitous infection with a spectrum ranging from mild to severe. The mystery regarding such variability in the clinical spectrum has not been fully unravelled, although a role for the complex interplay among virus characteristics, host immune response and environmental factors has been suggested. Antivirals and current vaccines have a limited role in prophylaxis and treatment because they primarily target surface glycoproteins which undergo antigenic/genetic changes under host immune pressure. Targeting conserved internal proteins could lead the way to a universal vaccine which can be used against various types/subtypes. However, this is on the distant horizon, so in the meantime, developing improved vaccines should be given high priority. In this review, we discuss where the current influenza research stands in terms of vaccines, adjuvants, and how we can better predict the vaccine strains for upcoming influenza seasons by understanding complex phenomena which drive the continuous antigenic evolution. PMID- 26885891 TI - Non-dioxin-like PCBs: a survey on fishery and aquaculture from the Mediterranean area. AB - A sampling campaign from 21 sites in Italy was conducted: 15 species from fishery and three species from aquaculture, for a total of 40 determinations, were considered. A careful sample preparation preceded the instrumental analysis that was carried out by means of GC-ECD and GC-MS. Good laboratory practice was achieved by the participation in proficiency tests, by the use of certified reference materials and by applying other directives recommended by international organisations. Concentrations measured in this work were compared with a TDI proposed by some international bodies: for a person weighing 70 kg one-third of the samples from fishery, when consumed, lead to exceed this TDI if the average fish daily consumption per capita is considered. Based on the data obtained here some hypotheses on environmental spreading and influence of PCBs on human health are made. Some suggestions about the preparation of fish for consumption are also given. PMID- 26885892 TI - Schizocalyx cuspidatus (A. St.-Hil.) Kainul. & B. Bremer extract improves antioxidant defenses and accelerates the regression of hepatic fibrosis after exposure to carbon tetrachloride in rats. AB - The aim of this study was to investigate the effect of leaves extract of Schizocalyx cuspidatus (A. St.-Hil.) Kainul. & B. Bremer on hepatic morphofunctional dysfunction induced by carbon tetrachloride (CCl4). Liver lesions were induced via intraperitoneal administration of CCl4 every 48 h for 12 days. Forty-nine rats were randomised into seven groups: G1: CCl4; G2: CCl4 (animals euthanised 24 h after last CCl4 application); G3: CCl4 + DMSO; G4: SCE 400 mg/kg; G5: DMSO (700 MUl); G6: CCl4 + SCE 200 mg/kg and G7: CCl4 + SCE 400 mg/kg. SCE administration resulted in reduction in hydroperoxide levels, lipidic droplets and necrosis compared to G1, G2 and G3. There was an increase in the amount of collagen fibres in G1, G2 and G3 compared to the groups. These results show that the extract of SCE leaves has great potential for the recovery of liver damage after the application of CCl4. PMID- 26885893 TI - A training program to enhance recognition of depression in nursing homes, assisted living, and other long-term care settings: Description and evaluation. AB - Low levels of symptom recognition by staff have been "gateway" barriers to the management of depression in long-term care. The study aims were to refine a depression training program for front-line staff in long-term care and provide evaluative knowledge outcome data. Three primary training modules provide an overview of depression symptoms; a review of causes and situational and environmental contributing factors; and communication strategies, medications, and clinical treatment strategies. McNemar's chi-square tests and paired t-tests were used to examine change in knowledge. Data were analyzed for up to 143 staff members, the majority from nursing. Significant changes (p < .001) in knowledge were observed for all modules, with an average change of between 2 and 3 points. Evidence was provided that participants acquired desired information in the recognition, detection, and differential diagnosis and treatment strategies for those persons at significant risk for a depressive disorder. PMID- 26885894 TI - Sex differences in genomics in lupus: girls with systemic lupus have high interferon gene expression while boys have high levels of tumour necrosis factor related gene expression. AB - OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic disease occurring up to 15 times more frequently in females than males. This bias extends to possible differences in disease flares and response to therapy. This study was initiated to investigate the differences between girls and boys with childhood-onset SLE (cSLE) at the molecular level. METHOD: We analysed the Gene Expression Omnibus National Center for Biotechnology Information (GEO NCBI) microarray data available for 88 girls and 16 boys with treatment-naive cSLE and compared the results to those from healthy controls. Transcriptional profiles were generated using the platforms of Affymetrix U133A and U133B gene chips and Bioconductor/R programming packages were used to process and compare the data. RESULTS: Girls with cSLE overexpressed an interferon (IFN)-alpha signature that was absent in boys. Boys with cSLE were observed to overexpress tumour necrosis factor-related genes that were absent in girls. Both boys and girls were observed to overexpress several genes related to granulopoeisis. CONCLUSIONS: Our results suggest a potential application of genomics to differentially predict response to therapy between females and males with SLE. PMID- 26885895 TI - Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration. AB - The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-beta-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features. PMID- 26885896 TI - Highlighting the impact of aging on type I collagen: label-free investigation using confocal reflectance microscopy and diffuse reflectance spectroscopy in 3D matrix model. AB - During aging, alterations of extracellular matrix proteins contribute to various pathological phenotypes. Among these alterations, type I collagen cross-linking and associated glycation products accumulation over time detrimentally affects its physico-chemical properties, leading to alterations of tissue biomechanical stability. Here, different-age collagen 3D matrices using non-destructive and label-free biophotonic techniques were analysed to highlight the impact of collagen I aging on 3D constructs, at macroscopic and microscopic levels. Matrices were prepared with collagens extracted from tail tendons of rats (newborns, young and old adults) to be within the physiological aging process. The data of diffuse reflectance spectroscopy reveal that aging leads to an inhibition of fibril assembly and a resulting decrease of gel density. Investigations by confocal reflectance microscopy highlight poor-fibrillar structures in oldest collagen networks most likely related to the glycation products accumulation. Complementarily, an infrared analysis brings out marked spectral variations in the Amide I profile, specific of the peptidic bond conformation and for carbohydrates vibrations as function of collagen-age. Interestingly, we also highlight an unexpected behavior for newborn collagen, exhibiting poorly-organized networks and microscopic features close to the oldest collagen. These results demonstrate that changes in collagen optical properties are relevant for investigating the incidence of aging in 3D matrix models. PMID- 26885897 TI - Nasal NK/T cell lymphoma presents with long-term nasal blockage and fever: a rare case report and literature review. AB - NK/T cell lymphoma (NKTCL) is a common disease which is a threat to human health. Nasal NKTCL is a rare but serious type of systemic lymphoma because of its high mortality rate and serious complications. In this case report, we describe a male who presented with nasal blockage in the right side, a fever of one month duration and a soy-like, painless and gradually increasing mass in the right submandibular region due to nasal NKTCL. The patient had no significant medical history and the initial clinical symptoms were nasal blockage. Contrast computed tomography showed that the nasopharyngeal mucosa was thickened and that the celiac and retroperitoneal lymphaden was intumescent. Finally a biopsy, guided by nasal endoscopy and examined using flow cytometry confirmed a diagnosis of NKTCL. Nasal NKTCL is rare and has no unique characteristics at first presentation, such as epidemiology and obvious clinical manifestation. As no effective therapy is currently available for this disease, early diagnosis and therapy of nasal NKTCL remains challenging. PMID- 26885899 TI - Integrative analysis of genome-wide association studies and gene expression analysis identifies pathways associated with rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a complex and systematic autoimmune disease, which is usually influenced by both genetic and environmental factors. Pathway analyses based on a single data type such as microarray data or SNP data have successfully revealed some biology pathways associated with RA. However, we found that the pathway analysis based on a single data type only provide limited understanding about the pathogenesis of RA. Gene-disease association is usually caused by many ways, such as genotype, gene expression and so on. Therefore, the integrative analysis method combining multiple levels of evidence can more precisely and comprehensively identify the pathway associations. In this study, we performed a pathway analysis by integrating GWAS and gene expression analysis to detect the RA-related pathways. The integrative analysis identified 28 pathways associated with RA. Among these pathways, 18 pathways were also found by both GWAS and gene expression analysis, 7 pathways are novel RA-related pathways, such as B cell receptor signaling pathway, Toll-like receptor signaling pathway, Fc gamma R mediated phagocytosis and so on. Compared with pathway analyses using only one type genomic data, we found integrative analysis can increase the power to identify the real associations and provided more stable and accurate results. We believe these results will contribute to perform future genetic studies in RA pathogenesis and may promote the development of new therapeutic strategies by targeting these pathways. PMID- 26885898 TI - Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling. AB - It is suggested that oxLDL is decisive in the initiation and development of atherosclerotic injuries. The up-regulation of oxidative stress and the generation of ROS act as key modulators in developing pro-atherosclerotic and anti-atherosclerotic processes in the human endothelial wall. In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs). Metformin also inhibited oxLDL increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels. However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries. These results provide a new insight regarding the possible molecular mechanisms of metformin. PMID- 26885900 TI - [Development of human embryonic stem cell platforms for human health-safety evaluation]. AB - The human embryonic stem cells (hESCs) serve as a self-renewable, genetically healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts. The evaluations were compared with those on the currently most adopted cellular platforms. Particularly, the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endothelial cells (HUVECs) were evaluated. The RESULTS showed that the standardized hESCs cellular platforms provided more sensitivity and accuracy for human cellular health-safety evaluation. PMID- 26885901 TI - [Relationships between microRNA expressions and prognosis in patients with tongue squamous cell carcinoma and the mechanisms microRNA regulating tongue squamous cell carcinoma biological behavior]. AB - Tongue squamous cell carcinoma (TSCC) is the most common type of oral cancer and is well known for its high rate of proliferation and lymph nodal metastasis. Exploring the underlying pathways regulating TSCC could provide novel ideas for diagnosis and prognosis of TSCC patients, as well as molecular targets for treatment of TSCC. MicroRNAs (miRNAs) are small noncoding RNAs that inhibit gene expression through the 3' untranslated regions (3'UTRs) of their target messenger RNAs. They play crucial roles in numerous biological processes, including cancer progression. Although great efforts have been made, what role miRNAs may play in the early detection and diagnosis of TSCC is not fully understood. Recently, our team has performed a series of basic and clinical researches in an attempt to investigate the relationships between miRNA expressions and prognosis of patients with TSCC and the mechanisms under regulation of TSCC. The results showed that miR-195, miR-34a, miR-29b, miR-375 and miR-26a could inhibit TSCC cells progression and development via a sophisticated network of genes. Specifically, the anti-tumor effects of miR-195 in TSCC may be partially mediated by its inhibition of CyclinD1 and Bcl-2 expression. The expression of miR-34a could inhibit migration and invasion of TSCC cell lines via targeting MMP9 and MMP14. The function of miR-29b may be through the miR-29b/Sp1/PTEN/AKT axis. Overexpression of miR-375 inhibited Sp1 expression by targeting the 3' untranslated region of the Sp1 transcript. MEG3 and miR-26a inhibited TSCC cell proliferation, cycle progression and promoted cell apoptosis and miR-26a could increase the MEG3 expression through reduction of the expression of DNMT3B in TSCC. In light of the role of those miRNAs in diagnosis and prognosis of TSCC, we reported that decreased miR-195 and miR-375 expression was associated with poor overall survival rate of the TSCC patients, while miR-34a expression was negatively correlated with cervical lymph node metastases. Furthermore, combined low expression levels of miR-26a and MEG3 emerged as an independent prognostic factor for poor clinical outcomes in TSCC patients, suggesting that combined miR 26a and MEG3 expression might prove useful as an independent biomarker of clinical prognosis among TSCC patients. PMID- 26885902 TI - [Association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis]. AB - OBJECTIVE: To investigate the potential association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis, which may provide benefits for diagnosis and treatment of aggressive periodontitis. METHODS: A total of 353 patients with aggressive periodontitis (group AgP) and 125 matched controls (group HP) were recruited in the study. Genotyping of FADS1 rs174537 and serum biochemical indexes were tested at the study's start. The relationships between the levels of TP, GLB, ALB, A/G and genotyping were analyzed. RESULTS: (1) The detection rate of allele G in group AgP was higher than that in group HP(68.1% vs. 61.2%, P=0.046,OR=1.35,95% CI 1.00-1.83); the detection rate of genotype GG in group AgP was higher than in group HP(45.5% vs. 34.4%,P=0.029, OR=1.60, 95% CI 1.05-2.44). (2) In group AgP, the patients with GG genotype exhibited significantly lower TP, GLB than the patients with GT+TT genotype [(77.08 +/- 7.88) g/L vs. (79.00 +/- 4.66) g/L, P=0.007; (28.17 +/- 7.63) g/L vs.(29.88 +/- 3.49) g/L,P=0.007) and the higher A/G(1.72 +/- 0.22 vs.1.67 +/- 0.22, P=0.040), but there was no significant difference in ALB between the patients with GG genotype and the patients with GT+TT genotype. In group HP, there were no significant differences in TP, GLB, A/G and ALB between individuals with genotype GT+TT and with genotype GG. (3)Compared with individuals with genotype GT+TT in group HP, the AgP patients with genotype GT+TT exhibited significantly higher TP, GLB [(79.00 +/- 4.66) g/L vs. (75.20 +/- 4.53) g/L, P<0.01; (29.88 +/- 3.49) g/L vs.(26.55 +/- 2.94) g/L, P<0.01) and the lower A/G(1.67 +/- 0.22 vs. 1.88 +/- 0.30, P<0.01), but there was no significant difference in ALB. There were no significant differences in TP, GLB, A/G and ALB the between the AgP patients with genotype GG and the healthy subjects with the same genotype either. CONCLUSION: FADS1 rs174537 polymorphism is associated with aggressive periodontitis. The patients with genotype GG in group AgP had relatively lower TP,GLB and higher A/G. Genotype GG might be a risk indicator for aggressive periodontitis by reducing host defense capability and contributing to inflammatory response in the occurrence and development of aggressive periodontitis. PMID- 26885903 TI - [Expression, roles and therapy target values of CD24 in oral squamous cell carcinoma]. AB - OBJECTIVE: To determine the expression profile and potential roles of CD24 in oral squamous cell carcinoma and explore the values of CD24 function as a potential target of clinical therapy. METHODS: Semi-quantitative immunohistochemistry was used to construct the expression profile of CD24 in 78 human oral tissues and 59 Hamster buccal pouch tissues. Real-time RT-PCR and Western blot were used to analyze the CD24 expression levels in oral DOK4 cells, oral cancer CAL-27 and WSU-HN6 cells. Then these two cancer cell lines were selected to evaluate the effect of all-trans retinoic acid (ATRA) and CD24 antibody on CD24 expression, and the proliferation and tumorsphere formation capacity of these two cell lines. RESULTS: CD24 expression was found significantly elevated in both human and animal tissues compared with normal and benign tissues (P<0.05), as well as in oral cancer CAL-27 and WSU-HN6 cells compared with DOK cells (P<0.05). CAL-27 and WSU-HN6 cells possess increased proliferative and specific tumorsphere formation capability compared with DOK cells (P<0.05). Both ATRA and CD24 antibody were able to effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells (P<0.05). Among them ATRA at least involved partially in the proliferation by down regulating the CD24 expression (P<0.05), while CD24 antibody blocking had no effect on the CD24 expression. CONCLUSION: CD24 was upregulated in oral cancer and functioned as a potential factor that promoted the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells. Both ATRA and CD24 antibody might effectively inhibit the proliferation and tumorsphere formation of CAL-27 and WSU-HN6 cells and function as a potential therapy target. PMID- 26885904 TI - [Effects of stromal cell-derived factor-1 on proliferation, migration, and odontoblastic differentiation of human dental pulp stem cells]. AB - OBJECTIVE: To compare the effects of stromal cell-derived factor-1 (SDF-1) and granulocyte colony-stimulating factor (G-CSF) on proliferation, migration, and odontoblastic differentiation of human dental pulp stem cell (DPSC) in vitro. METHODS: DPSCs were cultured in vitro and treated with either 100 MUg/L SDF-1 or 100 MUg/L G-CSF. Cell counting kit-8 (CCK-8) and colony-forming unit (CFU) were used to detect the effect of SDF-1 and G -CSF on the proliferation ability of DPSC. Cell migration of DPSC was determined by wound healing assay and Transwell migration assay. The effects of SDF-1 and G-CSF on odontoblastic differentiation of DPSC were evaluated by alkaline phosphatase (ALP) staining, ALP activity and alizarin red S staining. The expression of odontoblastic-related genes such as dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) were quantified by real-time RT-PCR. RESULTS: SDF-1 and G-CSF promoted the proliferation of DPSC slightly, but the difference was not statistically significant. Wound healing assay showed that SDF-1 and G-CSF promoted cell migration of DPSC significantly (P<0.01), but there was no significant difference between the two factors. In Transwell migration assay, the number of migrated cells of the control group was 5.0 +/- 1.4 per sight, while the SDF-1 group was 24.3 +/- 6.8 per sight and the G-CSF group was 11.8 +/- 3.3 per sight, suggesting that cell migration of DPSC was improved significantly after being treated with SDF-1 or G-CSF, and SDF-1 was more effective than G-CSF (P<0.05). Significantly greater odontoblastic differentiation potential was found in SDF-1 group and G CSF group based on the ALP staining. Higher ALP activity, more mineralization nodule formation and higher expressions of DMP-1 and DSPP were also found after SDF-1 or G-CSF treatment. CONCLUSION: SDF-1 had no significant effect on the proliferation of DPSC, but could significantly promote cell migration and odontoblastic differentiation of DPSC. Its effect on DPSC was better than G-CSF. PMID- 26885905 TI - [Histological changes in the circum-maxillary sutures during alternate maxillary expansions and constrictions in a rat model]. AB - OBJECTIVE: To investigate changes in the circum-maxillary sutures during alternate maxillary expansions and constrictions in a rat model. METHODS: Twenty two male Sprague-Dawley rats (6 weeks old) were used and divided into three groups. In maxillary expansion (ME) group (n=9), an expander was activated for 5 d, and then sacrificed. In alternate maxillary expansions and constrictions (Alt MEC) group (9 animals), an alternate expansion and constriction protocol (5 d expansion and 5 d constriction for one cycle) was conducted for 2.5 cycles (25 d total), and then sacrificed. The control group comprised 4 animals with no appliances used, each of two sacrificed on day 5 and day 25, respectively. Circum maxillary sutures (mid-palatal, maxillopalatine, premaxillary, zygomaticotemporal, and frontonasal suture) in each group were characterized histologically. RESULTS: Histological findings of circum-maxillary sutures: in control group, the normal sutures were divided into 5 zones, the center was polygon mesenchyme zone, the lateral was mature chondrocyte zone, the next lateral was bone tissue. In ME group, the mid-palatal suture was expanded after ME, the fibre and connective tissue were extracted and invaded into cartilage zone. Osteoblast hyperplasia and new bone formation occurred. The orientation of the new bone trabecula was consistent with force. The osteoclast appeared in some area. Findings of other sutures were similar with those of control group, osteogenesis was active in some area without obvious reconstruction in Alt-MEC group, mid-palatal suture and other sutures in some area were widened after Alt MEC with much more osteoblast hyperplasia and new bone formation. Fibre and connective tissue were extracted, distorted or even broken. Sutures in some areas were narrowed with osteoblast cytopenia and osteoclast hyperplasia. Fibre and connective tissue compressed because of the different force and orientation. Osteoclast count results showed that compared with the control group, the number of the osteoclast was increased only in the palatal suture in ME group (P<0.05). Other sutures did not show obvious changes (P>0.05). In Alt-MEC group, the numbers of the osteoclast in circum-maxillary sutures were the most, and had statistical significances (P<0.05). CONCLUSION: These RESULTS suggested that circum -maxillary sutures were actively reconstructed after Alt-MEC. while only midpalatal suture had active reaction after ME. PMID- 26885906 TI - [Promoted role of bone morphogenetic protein 2/7 heterodimer in the osteogenic differentiation of human adipose-derived stem cells]. AB - OBJECTIVE: To investigate the role of bone morphogenetic protein 2/7 heterodimer (BMP-2/7) in the osteogenesis of human adipose-derived stem cells (hASCs). METHODS: hASCs were exposed to three different treatments in vitro: osteogenic medium with 150 MUg/L BMP-2/7 (experimental group), osteogenic medium alone (OM group) and proliferation medium (PM group). After 1, 4 and 7 days of osteogenic induction, the amount of cellular DNA was measured to investigate the cytotoxicity. After 7 and 14 days, alkaline phosphatase (ALP) staining and quantification were performed to test the activity of ALP. After 21 and 28 days, the calcification deposition was determined by Alizarin Red S (ARS) staining and quantification. The expressions of the osteoblast-related genes were tested on days 1, 4, 7 and 14. In the in vivo study, 6 nude mice were used and 4 groups were set and implanted subcutaneously into the back of nude mice: (1) beta-TCP scaffold only (scaffold control group); (2) beta-TCP scaffold with hASCs cultured by PM in vitro for 1 week (PM control group); (3) beta-TCP scaffold with hASCs cultured by OM in vitro for 1 week (OM control group); (4) beta-TCP scaffold with hASCs cultured by OM with 150 MUg/L BMP-2/7 in vitro for 1 week (test group). After 4 weeks of implantation, histological staining was performed to evaluate the in vivo osteogenesis of hASCs. RESULTS: After induction for 1 day, there was no significant difference between the experimental group and the PM group on the cellular DNA content (P>0.05). After 4 days, the cellular DNA content increased under the stimulation of BMP-2/7 (P<0.05). On day 7, there was no significant difference among the three groups (P>0.05). ALP activity was higher by the induction of BMP-2/7 than in OM alone and PM (P<0.05). More mineralization deposition and more expressions of osteoblast-related genes such as Runx2, ALP, COL-1A1 and OC were determined in the experimental group at different time points (P<0.05). HE staining showed that, in the test group and OM control group, the extracellular matrix (ECM) with eosinophilic staining were observed around hASCs, and newly-formed bone-like tissues could be found in ECM around the scaffold materials. Moreover, compared with the OM control group, more bone-like tissues could be observed in ECM with typical structure of bone tissue in the test group. Masson's trichrome staining showed that more expression of collagen could be observed in ECM in the test group compared with the other groups. There was small amount of expression of collagen in the OM and PM control groups. No obvious positive results were found in the scaffold group. CONCLUSION: BMP-2/7 heterodimer plays a significant role in the osteogenesis of hASCs and is able to enhance the osteogenic differentiation of hASCs in vitro and in vivo. PMID- 26885907 TI - [Osteogenesis of human adipose-derived mesenchymal stem cells-biomaterial mixture in vivo after 3D bio-printing]. AB - OBJECTIVE: To construct human adipose-derived mesenchymal stem cells (hASCs) biomaterial mixture 3D bio-printing body and detect its osteogenesis in vivo, and to establish a guideline of osteogenesis in vivo by use of 3D bio-printing technology preliminarily. METHODS: P4 hASCs were used as seed cells, whose osteogenic potential in vitro was tested by alkaline phosphatase (ALP) staining and alizarin red staining after 14 d of osteogenic induction. The cells were added into 20 g/L sodium alginate and 80 g/L gelatin mixture (cell density was 1 * 10(6)/mL), and the cell-sodium alginate-gelatin mixture was printed by Bioplotter 3D bio-printer (Envision company, Germany), in which the cells'survival rate was detected by live- dead cell double fluorescence staining. Next, the printing body was osteogenically induced for 1 week to gain the experimental group; and the sodium alginate-gelatin mixture without cells was also printed to gain the control group. Both the experimental group and the control group were implanted into the back of the nude mice. After 6 weeks of implantation, the samples were collected, HE staining, Masson staining, immunohistochemical staining and Inveon Micro CT test were preformed to analyze their osteogenic capability. RESULTS: The cells'survival rate was 89%+/- 2% after printing. Six weeks after implantation, the samples of the control group were mostly degraded, whose shape was irregular and gel-like; the samples of the experimental group kept their original size and their texture was tough. HE staining and Masson staining showed that the bone-like tissue and vessel in growth could be observed in the experimental group 6 weeks after implantation, immunohistochemical staining showed that the result of osteocalcin was positive, and Micro CT results showed that samples of the experimental group had a higher density and the new bone volume was 18% +/- 1%. CONCLUSION: hASCs -biomaterial mixture 3D bio-printing body has capability of ectopic bone formation in nude mice, and it is feasible to apply cells-biomaterial mixture 3D bio-printing technology in the area of bone formation in vivo. PMID- 26885908 TI - [Influence of the occlusal interference time on masticatory muscle mechanical hyperalgesia in rats]. AB - OBJECTIVE: To investigate the relationship between the removal time of 0.2 mm occlusal interference and the recovery of masticatory muscle mechanical hyperalgesia in rats. METHODS: Forty male Sprague-Dawley rats (200-220 g) were randomly assigned to eight groups, with five rats in each group: (1) naive group: these rats were anesthetized and their mouths were forced open for about 5 min (the same duration as the other groups), but restorations were not applied; (2) sham-occlusal interference control group: bands were bonded to the right maxillary first molars which did not interfere with occlusion; (3)occlusal interference group: 0.2 mm thick crowns were bonded to the right maxillary first molars; (4) 2, 3, 4, 5, and 6 d removal of occlusal interference groups: 0.2 mm thick crowns were bonded to the right maxillary first molars and removed on days 2, 3, 4, 5, and 6. The naive group and sham-occlusal interference control group were control groups. The other groups were experimental groups. Bilateral masticatory muscle mechanical withdrawal thresholds were tested on pre application days 1, 2, and 3, and on post-application days 1, 3, 5, 7, 10, 14, 21 and 28. The rats were weighed on pre-application day 1 and on post-application days 1, 2, 3, 4, 5, 6, and 7. RESULTS: Between the naive group and the sham occlusal interference control group, there was no significant difference in the masticatory muscle mechanical withdrawal threshold of bilateral temporalis and masseters at each time point. No significant difference was detected between the contralateral side and ipsilateral side in experimental groups (P>0.05). In the 2, 3, 4, and 5 d removal of occlusal interference groups, the masticatory muscle mechanical withdrawal thresholds decreased after occlusal interference and increased after removal of the crowns and recovered to the baseline on days 7, 10, 14, and 14, respectively [the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (137.46 +/- 2.08) g, (139.02 +/- 2.11) g, (140.40 +/- 0.98) g, (138.95 +/- 0.98) g, respectively]. In the 6 d removal of occlusal interference group, the masticatory muscle mechanical withdrawal threshold increased after removal of the crowns and became stable since day 14. There was a significant difference between the 6 d removal of occlusal interference group and the sham-occlusal interference group on day 28 (P<0.05), the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (131.24 +/- 0.76) g and (141.34 +/- 1.43) g, respectively. CONCLUSION: After removal of the 0.2 mm thick crown within 5 days, the mechanical hyperalgesia of the rats could reverse completely. The mechanical hyperalgesia of the rats could only be relieved, but not reverse completely after removal of the 0.2 mm thick crown on day 6. As the time went on, even minor occlusal interference could cause irreversible mechanical hyperalgesia of masticatory muscles. This study suggested that occlusal interference caused by dental treatment should be eliminated as soon as possible, to avoid irreversible orofacial pain. PMID- 26885910 TI - [Effects of different fibre diameter of polypyrrole after direct current stimulation on adhesion and proliferation of cells and bacteria]. AB - OBJECTIVE: To study the effects of cells'and bacteria's adhesion and proliferation on different fiber diameters of polypyrrole coating with electricity. METHODS: Titanium coated with polypyrrole was divided into no electrical stimulation and stimulation groups, each group had 30-60 nm, 70- 100 nm, 130-170 nm diameters of the fiber. MC3T3 cells and Staphylococcus aureus (S. aureus) were inoculated on different fiber diameters of polypyrrole coating with and without electric stimulation. We gave the electrical stimulation group 100 mV for 1 h and every 24 hours gave it 1 h stimulation, and no electrical stimulation group was not managed. We used scanning electron microscope (SEM) to observe the cells'and bacteria's morphology. The cells were given 20 mL CCK-8 solutions after 1,3,7 days' cultivation, then incubated for 2 h, the solution was transferred to 96-well plate, we measured the cells' CCK-8 of the 30-60 nm, 70-100 nm, and 130 170 nm groups by Elisa. The cells on different fiber diameters were also stained by live-dead cell staining kit, TritonX-100 and DAPI. We used PBS to wash and glycerin to seal them. The live-dead situation and morphology were tested by co focal microscope. The bacterial were stained by Live/dead baclight bacterial viability kits, we detect the suspension's D of the 30-60 nm, 70-100 nm, and 130 170 nm groups, and also observed the bacteria's survival situation by co focal microscope. RESULTS: The CCK-8 of the cells with direct current stimulation was higher than that of the unpowered group (F=12.248, P=0.006). The smaller the fiber diameter, the better was the cell's adhesion and proliferation (F=9.261, P=0.005). The bacterial suspension's D of the electric group was lower than that of the unpowered group, and the fiber diameter had no significant effect on the bacteria's growth(F=9.641, P=0.036). CONCLUSION: Polypyrrole coating with electricity can promote the cell's proliferation and inhibit the bacteria's proliferation, and the cell growth on small fiber diameter coating is better. There is no difference in the bacterial growth of different fiber diameter coatings. PMID- 26885909 TI - [Antibacterial effect of self-etching adhesive systems on Streptococcus mutans]. AB - OBJECTIVE: To investigate the antibacterial effect of different self-etching adhesive systems against Streptococcus mutans (S. mutans). METHODS: Six reagents Clearfil(TM) SE Bond primer (SP), Clearfil(TM) SE Bond adhesive (SA),Clearfil(TM) Protect Bond primer (PP), which contained antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB), ClearfilTM Protect Bond adhesive (PA), positive control chlorhexidine acetate [CHX, 1% (mass fraction)], and negative control phosphate buffer solution (PBS) were selected. They were mixed with S. mutans for 30 s respectively, then colony-forming units (CFU) were counted after incubated for 48 h on brain heart infusion (BHI) agar medium. The 6 reagents were applied to the sterile paper discs, and distributed onto the BHI agar medium with S. mutans and incubated for 24 h, then the inhibition zones were observed. CHX, PBS, PP, and SP were added on the dentin with artificial caries induced by S. mutans and kept for 30 s, then confocal laser scanning microscope (CLSM) was used to observe the live and dead bacteria after staining. The ratio of live to dead bacteria was calculated. PP+PA and SP+SA were applied on the dentin according to the manual and light cured. S. mutans were incubated on the samples for 2 h, ultrasonically treated and incubated on BHI agar medium for 48 h, then CFU was counted. The data were analyzed by non-parametric analysis and one-way ANOVA. RESULTS: Compared with PBS, the PP, SP, PA, SA and CHX showed the antibacterial effect on free S. mutans (P<0.05); SP and PP showed stronger antibacterial effect than PA, SA and CHX (P<0.05). CHX, SP and PP presented inhibition zones, while PBS, SA and PA did not. Compared with PBS, the CHX, SP and PP could lower the ratio of the live to dead bacteria significantly (P<0.05). Cured self-etching adhesive systems did not show any antibacterial effect on the free S. mutans. CONCLUSION: The primer of self-etching adhesives Clearfil(TM) SE Bond and Clearfil(TM) Protect Bond showed significant antibacterial effect on free and attached S. mutans. The adhesive only showed antibacterial effect on free S. mutans before light-cured polymerization. After being cured, the self etching adhesive systems did not show antibacterial effect anymore. PMID- 26885911 TI - [Effects of Er, Cr: YSGG laser on the root surface of periodontitis and healthy teeth]. AB - OBJECTIVE: To evaluate the effects of Er, Cr: YSGG laser on the root surface of periodontally involved teeth and healthy teeth, concerning the microstructure and the roughness. METHODS: Eight freshly extracted teeth due to severe periodontitis and eight freshly extracted teeth due to orthodontic reasons or being third molar were chosen in this study. The root surface of each tooth was divided into four areas, and received four treatment METHODS: no treatment (control group); root planing with Gracey scaler for 30 seconds; irradiation by the lower power Er, Cr: YSGG laser; irradiation by the higher power Er, Cr: YSGG laser. Four periodontally involved teeth and four healthy teeth were used for the evaluation of microstructure using scanning electron microscope (SEM). The other four periodontitis teeth and four healthy teeth were used for the evaluation of roughness (Ra value) using 3D profiler. RESULTS: Smear layer was found on the teeth scaled by Gracey scaler, while the teeth irradiated by Er, Cr: YSGG laser demonstrated a melting surface with less smear layer. In the periodontitis teeth irradiated by the higher power, opening dentinal tubules could be observed. For the periodontally involved teeth, the Ra values of groups 1 to 4 were (237.4 +/- 20.0) nm, (135.7 +/- 11.9) nm (P=0.01), (463.6 +/- 49.3) nm (P<0.001) and (486.0 +/- 59.0) nm (P<0.001) respectively. For the healthy teeth, the Ra values of groups 1 to 4 were (191.4 +/- 44.5) nm, (131.6 +/- 21.5) nm (P=0.482), (463.7 +/- 34.6) nm (P<0.001) and (470.3 +/- 121.3) nm (P<0.001) respectively. CONCLUSION: Er, Cr: YSGG laser can affect the microstructure of the cementum of the periodontitis teeth and healthy teeth. Irradiation by the Er, Cr: YSGG laser resulted in a melting surface with less smear layer and increased the roughness in the surface of root. PMID- 26885912 TI - [Application of anaerobic bacteria detection in oral and maxillofacial infection]. AB - OBJECTIVE: To investigate the distribution and drug resistance of anaerobic bacteria in the patients with oral and maxillofacial infection. METHODS: Aerobic and anaerobic bacteria cultures from 61 specimens of pus from the patients with oral and maxillofacial infection in the Department of Oral and Maxillofacial Surgery, Peking University School of Stomatology were identified. The culture type was evaluated by API 20A kit and drug resistance test was performed by Etest method. The clinical data and antibacterial agents for the treatment of the 61 cases were collected, and the final outcomes were recorded. RESULTS: The bacteria cultures were isolated from all the specimens, with aerobic bacteria only in 6 cases (9.8%), anaerobic bacteria only in 7 cases (11.5%), and both aerobic and anaerobic bacteria in 48 cases (78.7%). There were 55 infected cases (90.2%) with anaerobic bacteria, and 81 anaerobic bacteria stains were isolated. The highest bacteria isolation rate of Gram positive anaerobic bacteria could be found in Peptostreptococcus, Bifidobacterium and Pemphigus propionibacterium. No cefoxitin, amoxicillin/carat acid resistant strain was detected in the above three Gram positive anaerobic bacteria. The highest bacteria isolation rate of Gram negative anaerobic bacteria could be detected in Porphyromonas and Prevotella. No metronidazole, cefoxitin, amoxicillin/carat acid resistant strain was found in the two Gram negative anaerobic bacteria. In the study, 48 patients with oral and maxillofacial infection were treated according to the results of drug resistance testing, and the clinical cure rate was 81.3%. CONCLUSION: Mixed aerobic and anaerobic bacteria cultures are very common in most oral and maxillofacial infection patients. Anaerobic bacteria culture and drug resistance testing play an important role in clinical treatment. PMID- 26885914 TI - [Determination of human papillomavirus in oral leukoplakia,oral lichen planus and oral squamous cell carcinoma]. AB - OBJECTIVE: To investigate the possibility for human papillomavirus (HPV) infection to be a predictable signal for the carcinogenesis of oral mucosa by comparing the prevalences of HPV in each stage of oral mucosal carcinogenesis and to compare the sensitivity differences of the two methods in detecting HPV infection in oral cavity. METHODS: The hybrid capture (HC-II) was used to detect infection of HPV in 255 samples taken from 12 cases of healthy oral mucosa, 211 cases of patients with pathological diagnosis and 32 cases of patients with clinical diagnosis. The diagnosed cases included 8 cases of benign lesions of the oral mucosa, precancerous lesions [74 cases of oral leukoplakia (OLK) with hyperplasia and 42 cases of OLK with oral epithelial dysplasia (OED)], 91 cases of precancerous condition [oral lichen planus (OLP)] and 28 cases of oral squamous cell carcinoma (OSCC). And in situ hybridization (ISH) was used to detect infection of HPV in 33 cases of OSCC and 76 cases of OLK, including 30 cases of hyperplasia, 15 cases of mild OED, 15 cases of moderate OED and 16 cases of severe OED. RESULTS: The prevalence of HPV in OLP samples was higher (12.12%, 8/66) than that of OLK (2.59%, 3/116) (chi(2)=4.666, P=0.031) and OSCC(7.14%, 2/28, chi(2)=0.513, P=0.474). The prevalence of HPV in OSCC (7.14%, 2/28) was higher than that of OLK (2.59%, 3/116), and no significant difference was found. There was only one case of smoke spot and statistical analysis was not carried out. ISH was used to detect type 16/18 and type 31/33 HPV DNA in 109 cases of oral mucosal lesions in paraffin sections and only one case of OSCC was HPV positive. Thirty-seven cases were detected by HC-II and ISH methods at the same time. The same negative results by the two methods were found in 94.6% samples (35/37). In the other two samples, one was OSCC with early infiltration and the other was OLK with hyperplasia, The HC-II results were positive while the ISH results were negative. The patients with OLP and HPV testing results were followed up and the average follow-up period was (36.2 +/- 10.5) months. It was found that three of them had a malignant transformation, and the malignant transformation rate of HPV positive patients was 12.50% (1/8), which was higher than that of HPV negative patients (3.45%, 2/58), and the difference was not statistically significant, P=0.249. CONCLUSION: HC-II assay was more sensitive in detecting HPV infection of oral mucosal lesions than ISH. The results of this study showed that there was insufficient evidence for taking HPV infection as a predictor of OLK carcinogenesis. Patients suffering from OLP were in a precancerous condition. The prevalence of HPV in OLP patients of this study was higher than that in OLK and OSCC patients, suggesting that for some reason, OLP patients were susceptible to HPV. HPV testing can be considered as routine in patients with OLP, and HC-II assay was recommended. And patients with OLP and HPV positive should be followed up regularly. PMID- 26885913 TI - [Clinical features of osteonecrosis of jaws after bisphosphonates therapy for bone metastasis of breast cancer]. AB - OBJECTIVE: To understand the clinical features of osteonecrosis of the jaw after bisphosphonates use for therapy of breast cancer patients with bone metastasis. METHODS: The cases diagnosed as bisphosphonates-related osteonecrosis of the jaws (BRONJ) were retrospectively analyzed from January 2011 to August 2015 in the Peking University School and Hospital of Stomatology, and those breast cancer patients with bone metastasis were selected. The clinical symptoms, imaging characteristics and treatment results were summarized. RESULTS: A total of 14 cases of breast cancer patients with bone metastasis were selected, with an average age of 60.21 years. The average time of suffering from breast cancer was 9.77 years, and the average time of bone metastasis and bisphosphonates drugs use was 5.67 and 3.29 years individually. There was no patient with systemic application history of hormone therapy, and no history of diabetes. There were 9 patients with tooth extractions history, and the mean time of bone necrosis symptoms was 8.58 months. There were 10 cases with bone necrosis occurring on mandible, 3 cases on maxilla, and one case with both upper and lower jaws involved. Among the 10 patients with surgical treatment, there were 3 cases cured, and 6 cases improved. However, the clinical symptoms of 2 cases with conservative treatment were significantly aggravated. CONCLUSION: The medication time between the bisphosphonates use beginning and the occurrence of BRONJ is relatively long. The history of diabetes and long-time hormone use did not exist in this group. Tooth extraction itself does not determine the severity of BRONJ. Mandible is the most common site involved by BRONJ. Surgical treatment can alleviate the clinical symptoms of BRONJ with breast cancer to some extent. PMID- 26885915 TI - [Risk assessment of different grades of hypertension during the treatment of patients with acute pulpitis]. AB - OBJECTIVE: To evaluate the vital signs changes, influence factors in different grades of hypertension patients during the treatment of acute pulpitis, in order to obtain the risk prevention measures. METHODS: In this study, 90 different grades of hypertension patients with acute pulpitis were recruited from February 2014 to February 2015 in the Department of Oral Emergency, Peking University School and Hospital of Stomatology. The information about the patients'general health, oral treatment, life signs of change information was collected. Patients were divided into high risk group, middle risk group, and low risk group (30 patients for each group). RESULTS: (1) Compared with the preoperative, systolic blood pressure (90%), diastolic blood pressure (80%), heart rate increase (100%) were increased in the high risk group. The increase rates of the middle risk group and the low risk group were significantly lower than those of the high risk group (P<0.01). At the same time, the systolic blood pressure of 1/4 (26.7%) patients in high risk group increased more than 20 mmHg (1 mmHg=0.133 kPa), and the diastolic blood pressure of 2/5 patients in high risk group increased more than 10 mmHg, the difference was statistically significant compared with the other two groups (P<0.05). (2) Compared with the preoperative, the average increase of the maximum peak were increased [systolic blood pressure (18.0 +/- 1.5) mmHg, diastolic blood pressure (8.0 +/- 1.7) mmHg], the mean of heart rate changes [(7.0 +/- 0.3) beats per minute] was also increased in the high risk group, while these two indicators were decreased in the low risk group and the middle risk group. The electrocardiogram (ECG) was changed in 6 cases during the treatment in the high risk group. No significantly changed were observed in the low risk group and the middle risk group. (3) Compared the risk assessment in preoperative with that in postoperative, in the middle risk group, 23 cases were evaluated as medium risk in final evaluation, 6 as low risk, and 1 as high risk (risk assessment increased); in the high risk group, 20 cases were evaluated as high risk, 7 as very high risk, and 3 as medium risk (risk assessment decreased). CONCLUSION: Oral treatment is very safe for patients with hypertension, but the risk factor, target organ damage, and complications will also increase the risk of cardiovascular events in elderly patients during the acute pulpitis treatment. Dentist should take some measures to avoid the risks. PMID- 26885916 TI - [Three-dimensional finite element analysis of influence of occlusal surface height on stress distribution around posterior implant-supported single crown]. AB - OBJECTIVE: To evaluate the effect of the occlusal surface height of a mandibular posterior implant-supported single crown on stress in bone tissues. METHODS: Three-dimensional finite element models of the implant-supported single crown replacing the missing right lower second premolar, mesial and distal natural teeth, periodontal membrane, alveolar bone, loaded rigid body and analog food of almond were established. Using the Federation Dentaire International (FDI) system, the first premolar, the second premolar and the first molar were represented with 44, 45, 46. Three occlusal surface heights of the crown were studied: (1) normal height; (2) 15 MUm reduction in height; (3) 30 MUm reduction in height. The models were loaded by independent loading with maximal occlusal force(44 by 280 N, 45 by 360 N, and 46 by 480 N) and average occlusal force(44 by 140 N, 45 by 180 N, and 46 by 240 N)on the single crown; combined loading (maximal occlusal force transformed into uniform load of 3.7 MPa on top of rigid body, in contact with points on the occlusal surface), and analog almond-like food loading (average occlusal force transformed into uniform load of 1.67 MPa in simulated food chewing, in contact with points on the occlusal surface). RESULTS: For maximal biting force under independent loading, Von Mises stress peak values in bone tissues around 44, 45, and 46 were 82.57 MPa, 45.26 MPa and 27.79 MPa; For average biting force, peak values were 41.28 MPa, 22.63 MPa and 13.89 MPa. Under combined loading, compared with the normal occlusal surface height group, Von Mises stress peak values decreased 4.6 MPa, by 0.84%; increased 7.52 MPa, by 20.04%, and decreased 1.8 MPa, by 5.84%, for 45, 46, and 44 in the 30 MUm infra occlusion group, respectively. Under food loading, Von Mises stress peak values decreased 0.34 MPa, by 1.62%; increased 1.11 MPa, by 2.66%; and increased 0.06 MPa, by 0.54%, and for 45, 46, and 44 in the 30 MUm infra-occlusion group, respectively. CONCLUSION: Within the limitation of this study, within 30 MUm reduction of the occlusal surface height of implant-supported single crown, no significant difference of the peak values was observed. PMID- 26885917 TI - [Comparison of effectiveness and safety between Twisted File technique and ProTaper Universal rotary full sequence based on micro-computed tomography]. AB - OBJECTIVE: To evaluate the efficacy and security of two type of rotary nickel titanium system (Twisted File and ProTaper Universal) for root canal preparation based on micro-computed tomography(micro-CT). METHODS: Twenty extracted molars (including 62 canals) were divided into two experimental groups and were respectively instrumented using Twisted File rotary nickel titanium system (TF) and ProTaper Universal rotary nickel titanium system (PU) to #25/0.08 following recommended protocol. Time for root canal instrumentation (accumulation of time for every single file) was recorded. The 0-3 mm root surface from apex was observed under an optical stereomicroscope at 25 * magnification. The presence of crack line was noted. The root canals were scanned with micro-CT before and after root canal preparation. Three-dimensional shape images of canals were reconstructed, calculated and evaluated. The amount of canal central transportation of the two groups was calculated and compared. RESULTS: The shorter preparation time [(0.53 +/- 0.14) min] was observed in TF group, while the preparation time of PU group was (2.06 +/- 0.39) min (P<0.05). In mid-root level, TF group shaping resulted in less canal center transportation than PU group [(0.070 +/- 0.056) mm vs. (0.097 +/- 0.084) mm, P<0.05]. No instrument separation was observed in both the groups. Cracks were not found in both the groups either based in micro-CT images or observation under an optical stereomicroscope at 25 * magnification. CONCLUSION: Compared with ProTaper Universal, Twisted File took less time in root canal preparation and exhibited better shaping ability, and less canal transportation. PMID- 26885918 TI - [A cone-beam computed tomography study on crown-root morphology of maxillary anterior teeth in Class II, division 2 malocclusion]. AB - OBJECTIVE: To study crown-root morphology of maxillary anterior teeth in Class II, division 2 malocclusion using cone-beam CT (CBCT) combined with computer aided measurement technology to provide guidance for clinical treatment. METHODS: The samples which consisted of 36 cases radiographed with CBCT techniques were selected and divided into two groups (18 each ) based on the type of malocclusion presented: Class II, division 2 group (group II 2) and Class I group (group I). The measurements of crown-root morphology including crown-root angle and surface shaft angle were got by Multiple Planer Reconstruction of CBCT data uploaded into InvivoDental software 5.0. The data were processed with SPSS 20.0 software package and t test was employed for comparison of angular measurements. RESULTS: In group I, crown-root angles of maxillary central incisor, maxillary lateral incisor and maxillary canines were 179.08 degrees +/- 3.31 degrees , 176.55 degrees +/- 2.77 degrees and 184.20 degrees +/- 2.51 degrees respectively, surface-shaft angles were 21.00 degrees +/- 2.63 degrees , 19.63 degrees +/-2 .35 degrees and 19.36 degrees +/- 2.30 degrees respectively. While in group II 2, crown-root angles of maxillary central incisor, maxillary lateral incisor and maxillary canines were 176.80 degrees +/- 2.62 degrees , 174.13 degrees +/- 3.28 degrees and 181.79 degrees +/- 2.88 degrees respectively, surface-shaft angles were 23.20 degrees +/- 2.95 degrees , 22.29 degrees +/- 2.19 degrees and 20.61 degrees +/- 2.34 degrees respectively. Compared with group I, significant statistical differences were observed with the exception of surface shaft angle of maxillary incisor. There was significant difference in crown-root angle between group II 2 and 180 degrees . CONCLUSION: The maxillary anterior teeth in Class II, division 2 malocclusion exhibited significant crown-root morphology which would influence the torque after orthodontic treatment. Special attention should be paid to the position of maxillary anterior teeth roots during orthodontic treatment for Class II, division 2 malocclusion. The ideal position of tooth movement should be decided by the root rather than the location of the crowns. PMID- 26885919 TI - [Study of anterior alveolar bone thickness in skeletal class III malocclusion patients with orthognathic surgery]. AB - OBJECTIVE: To investigate the compensation of the anterior alveolar bone thickness in skeletal class III patients treated with orthodontic-surgical treatment. METHODS: The samples consisted of 54 skeletal class III patients treated with orthodontic-surgical treatment. Lateral cephalograms were taken before treatment. Descriptive statistics were calculated for corresponding variables, and the differences between the samples and the norms from Peking University normal occlusion sample library were assessed by independent-sample t test. Correlation analyses were performed to find associations between skeletal characteristics and anterior alveolar bone thickness. According to skeletal anteroposterior discrepancy/vertical type (ANB, criteria=-4 degrees ; SN-MP, criteria=37.7 degrees ), the samples were allocated into group A (severe anteroposterior discrepancy/hypodivergent vertical type, n=11), group B (moderate anteroposterior discrepancy/hypodivergent vertical type, n=16), group C (severe anteroposterior discrepancy/hyperdivergent vertical type, n=14), and group D (moderate anteroposterior discrepancy/hyperdivergent vertical type, n=13),and one way ANOVA with SNK multiple comparison test were performed. RESULTS: The anterior alveolar bone thickness of the skeletal class III patients were thinner compared with norm values (P<0.05). Correlational analyses showed that,both the upper and lower anterior alveolar bone thickness was correlated with the skeletal vertical discrepancy (P<0.05), but the anteroposterior type was only correlated with the lower anterior alveolar bone thickness (P<0.05). For the 4 groups according to skeletal anteroposterior discrepancy/vertical type, hypodivergent vertical type had thinner lower ligual and total bone thickness (LP, LW, P<0.05). while for upper alveolar bone thickness (UW), group C and group B exhibited the thinnest and thickest (the values of UW were 7.86 mm and 9.05 mm). CONCLUSION: The upper and lower anterior alveolar bone thickness of skeletal class III patients are thinner compared with normal occlusion. Different skeletal anteroposterior discrepancy/vertical type results in differences in the anterior alveolar bone thickness, so decompensation should be treated differently and carefully. PMID- 26885920 TI - [Bonding strength of resin and tooth enamel after teeth bleaching with cold plasma]. AB - OBJECTIVE: To investigate the immediate bond strength and surface structure of resin and the tooth enamel which treated by cold plasma. METHODS: In the study, 40 bovine incisors were divided into two equal parts. In this sense, all enamel adhesive samples were prepared and then randomly divided into 4 groups (n =20). group 1: acid + single bond 2+resin composite (control group); group 2:beyond bleaching+ acid+single bond 2+resin composite; group 3: treated by cold plasma for 5 minutes+ acid+single bond 2+resin composite; group 4: treated by cold plasma for 5 minutes+single bond 2+resin composite. Single bond 2 bonding system and Filtek Z250 resin were used in this experiment. The shear bond strength was tested by universal testing machine. The surface of the enamel in different processes was observed by scanning electron microscope (SEM). Statistical analyses by the single factor analysis of variance and multiple pairwise comparisons were performed with SPSS 17.0 . RESULTS: The shear bond strength of group 4 (8.60 MPa) was significantly lower than that of the other three groups (P<0.05). The shear bond strength of group 2 (17.89 MPa) was higher than that of group 4, but lower than group 1 and group 3 (P<0.05).There was no significant difference between group 1 (34.82 MPa) and group 3 (34.69 MPa). Scanning electron microscope indicated that the enamel treated by cold plasma had slight molten form, which was different from etched enamel surface.The fractured surface of group 3 was mix fracture, which was similar to the control group (group 1). CONCLUSION: Compared with the conventional clinic bleaching, immediate bond strength of resin-enamel that treated by cold plasma has not been affected. PMID- 26885921 TI - [Evaluation of alveolar ridge reconstruction and esthetic result following immediate implant]. AB - OBJECTIVE: To evaluate the bone alteration subject to remodeling and analyze the esthetic result following immediate implant placement of incisors. METHODS: In this study, 20 patients (13 women, 7 men) were involved, who needed implants for incisors of maxilla. The patients received 23 immediate implants totally. On the day of surgery and 6 months after the implants were placed, Cone beam CT (CBCT) was taken. The thickness of the alveolar ridge and the vertical change of marginal bone levels onthe mesial and distal aspects of theimplants were measured using the computer software (PlanmecaRomexis Viewer 3.6.0.R). The evaluation of esthetic result by labial convexity score (LCS) and papilla index score (PIS) were analyzed pre-operation and one year after the final crown was delivered. The statistics with paired-t test for the measurement data and Willcoxon test for rating data were done by SPSS 20.0. RESULTS: The survival rate in the two-year follow-up was 100%. The measuring point 1 (MP1), MP2, MP3 and MP4 (0, 2, 4, 6 mm apical to the implant platform, respectively) got significant alterations after 6 months of the follow-up. These differences were statistically significant (P<0.05).The major alteration happened at MP1 and MP4, which got (-0.89 +/- 2.06) mm and (-0.75 +/- 1.28) mm reduction of the alveolar, respectively. The marginal alveolar ridge resorption was (-0.42 +/- 1.24) mm and(-0.91 +/- 1.96) mm for Ankylos System and Replace System, respectively, and the difference was not statistical significant . The esthetic results were quite acceptable. Before treatment, 18 incisors rated 3 for LCS, and 2 incisors rated 4 for LCS;after final restoration, only 5 incisors rated 3 for LCS, and 14 incisors rated 2 for LCS. Before treatment, 15 incisors rated 3 for PIS; after final restoration, 13 incisors rated 3 for PIS. There was no statistically significant difference for the PIS pre-operation and 1 year after final restoration, while there was statistically significant negative change for LCS. CONCLUSION: Even following the proper surgical technique, the alveolar ridge wall still can't be maintained after immediate implant placed in fresh socket of incisors. The inter-dental papilla could be well maintained, while due to the remodeling of labial bone, labial convexity will inevitably collapse. Therefore immediate implant still has esthetic risk. PMID- 26885922 TI - [Evaluation with different measuring methods for the alveolar bone change of ridge preservation in molar sites]. AB - OBJECTIVE: To investigate the changes of the vertical height and width of the alveolar bone six months after the alveolar ridge preservation in periodontal compromised molar sites of severe alveolar bone defects with clinical direct measurement, parallel periapical radiographs, and cone-beam computed tomography (CBCT), and to analyze the effect of the three different methods of measurement. METHODS: In this study, 20 subjects requiring tooth extraction on account of periodontal disease with a total of 23 extracted molars were enrolled. Extractions were performed atraumatically and patients were received alveolar ridge preservation procedure with Bio-Oss and Bio-Gide. Clinical direct measurements were taken after tooth extraction and during the implant surgery 6 months later, CBCT scans and parallel periapical radiographs were taken immediately after ridge preservation and 6 months later. The changes of alveolar ridge width and vertical height after six months were measured and analyzed through the above-mentioned three methods and the similarities and differences of the measured effect were compared. RESULTS: There were no significant difference of alveolar vertical height in the center of the extraction sites, the center of distal aspect, and distobuccal aspect between the clinical direct measurements and the CBCT measurements (P>0.05), alveolar vertical height in other points and alveolar width measurements were statically significant (P<0.05). After 6 months, 10 sites of 10 subjects were received a flap and re-entered to perform dental implants surgery. The vertical height in the center of alveolar increased significantly and the changes of alveolar vertical height of clinical direct and CBCT measurement were (6.15 +/- 1.73) mm and (6.59 +/- 2.53) mm, respectively. The measurements of the width of the alveolar bone were (8.45 +/- 1.18) mm and (8.52 +/- 1.27) mm, respectively. The measurements of the two methods were not statistically significant (P>0.05). The change of the alveolar height in the center of the extraction socket after six months measured by parallel periapical was (5.84 +/- 4.28) mm, which was closed to the clinical direct measurement and the CBCT measurement. CONCLUSION: Clinical direct measurement and CBCT measurement were largely consistent in the evaluation of the alveolar bone height and width after the alveolar ridge preservation using deproteinized boving bone mineral (DBBM, Bio-Oss) and bioabsorbable collagen membrane (Bio-Gide) in periodontal compromised molar sites of severe bone defects. PMID- 26885923 TI - [Clinical evaluation of "All-on-Four" provisional prostheses reinforced with carbon fibers]. AB - OBJECTIVE: To assess the clinical effects of carbon fiber reinforcement on the "All-on-Four" provisional prostheses. METHODS: Provisional prostheses were divided into control group and carbon fiber reinforcing group according to whether carbon fiber reinforcement was used in the provisional prostheses base resin. In our study, a total of 60 patients (32 males and 28 females) with 71 provisional prostheses(28 maxilla and 43 mandible)were enrolled between April 2008 and December 2012 for control group; a total of 23 patients (13 males and 10 females) with 28 provisional prostheses (9 maxillas and 19 mandibles) were enrolled between January 2013 and March 2014 for carbon fiber reinforcing group. The information of provisional prostheses in the patients was recorded according to preoperative examination. We used the date of definitive prosthesis restoration as the cut-off point, observing whether fracture occurred on the provisional prostheses in the two groups. Additionally we observed whether fiber exposure occurred on the tissue surface of the provisional prostheses and caused mucosal irritation. The interface between the denture base resin and the fibers was examined using scanning electron microscopy (SEM). RESULTS: The age [(57.3 +/ 10.1) years vs.(55.1 +/- 11.4) years], gender (32 males and 28 females vs. 13 males and 10 females), maxilla and mandible distributions (28 maxillas and 43 mandibles vs. 9 maxillas and 19 mandibles), the number of extraction jaws (46 vs. 23), the average using time [(7.8 +/- 1.3) months vs. (7.5 +/- 1.1) months], and the opposing dentition distributions of provisional prostheses of the patients showed no significant differences between the control and reinforcing groups. There were 21(29.6%) fractures that occurred on the 71 provisional prostheses in the control group; there was no fracture that occurred on the 28 provisional prosthesesin the carbon fiber reinforcing group. The fracture rate of the carbon fiber reinforcing group was significantly lower than that of the control group (P=0.001). No carbon fiber exposure and mucosal irritation were observed from clinical examination.SEM revealed relatively continuous contact between the fiber and acrylic resin, and the resin particles adhered on the surface of the carbon fibers. CONCLUSION: The addition of carbon fibers between abutments placed on "All-on-Four" provisional fixed denture base resin may be clinically effective in preventing "All-on-Four" denture fracture and can provide several advantages for clinical use. PMID- 26885924 TI - [Constructing 3-dimensional colorized digital dental model assisted by digital photography]. AB - OBJECTIVE: To explore a method of constructing universal 3-dimensional (3D) colorized digital dental model which can be displayed and edited in common 3D software (such as Geomagic series), in order to improve the visual effect of digital dental model in 3D software. METHODS: The morphological data of teeth and gingivae were obtained by intra-oral scanning system (3Shape TRIOS), constructing 3D digital dental models. The 3D digital dental models were exported as STL files. Meanwhile, referring to the accredited photography guide of American Academy of Cosmetic Dentistry (AACD), five selected digital photographs of patients'teeth and gingivae were taken by digital single lens reflex camera (DSLR) with the same exposure parameters (except occlusal views) to capture the color data. In Geomagic Studio 2013, after STL file of 3D digital dental model being imported, digital photographs were projected on 3D digital dental model with corresponding position and angle. The junctions of different photos were carefully trimmed to get continuous and natural color transitions. Then the 3D colorized digital dental model was constructed, which was exported as OBJ file or WRP file which was a special file for software of Geomagic series. For the purpose of evaluating the visual effect of the 3D colorized digital model, a rating scale on color simulation effect in views of patients'evaluation was used. Sixteen patients were recruited and their scores on colored and non-colored digital dental models were recorded. The data were analyzed using McNemar-Bowker test in SPSS 20. RESULTS: Universal 3D colorized digital dental model with better color simulation was constructed based on intra-oral scanning and digital photography. For clinical application, the 3D colorized digital dental models, combined with 3D face images, were introduced into 3D smile design of aesthetic rehabilitation, which could improve the patients' cognition for the esthetic digital design and virtual prosthetic effect. CONCLUSION: Universal 3D colorized digital dental model with better color simulation can be constructed assisted by 3D dental scanning system and digital photography. In clinical practice, the communication between dentist and patients could be improved assisted by the better visual perception since the colorized 3D digital dental models with better color simulation effect. PMID- 26885925 TI - [Prospective and controlled study on effect of fortified human milk feeding on infants with extremely and very low birth weight during hospital stay]. AB - OBJECTIVE: To explore the effect of fortified human milk feeding on growth and complications of infants with extremely and very low birth weight (ELBW/VLBW) during hospital stay by a prospective, random and controlled study. METHODS: In the study, 122 ELBW/VLBW infants were enrolled and divided into two groups. The infants fed with human breast milk, combined with human milk fortification (HMF) during hospital stay were named HMF group (n=62), and those fed exclusively with premature formula were named premature formula feeding group (PF group, n=60). The data of the infants'growth (the velocity of increase on the weight, length, head circumference and upper arm circumference), the time of rebounding to birth weight, the time of needing intravenous nutrition, the time of hospitalizing, the proportion of extrauterine growth retardation (EUGR) during hospital stay, the level of hemoglobin, bone metabolism and incidence of complications were compared between the two groups. RESULTS: Among the 122 infants included, (1) the length increment in HMF group was higher than PF group [(0.89 +/- 0.23) cm/week vs. (0.79 +/- 0.34) cm/week, P=0.04]; there were no significant differences in the weight gain, head circumference increment and upper arm circumference increment (P>0.05); (2) the age of rebounding to birth weight [(10.13 +/- 4.03) d vs. (8.03 +/- 3.28) d, P=0.002] and the duration of intravenous nutrition [(16.77 +/- 6.63) d vs. (14.23 +/- 4.15) d, P=0.01] in HMF group were longer than that in PF group, there were no significant differences between the two groups in the hospital stay and age achieved feeding; (3) there were no significant differences between the two groups in the incidence rate of EUGR during hospital stay (P>0.05); (4) the level of calcium at birth in HMF group was lower than that in PF group [(2.19 +/- 0.22) mmol/L vs.( 2.32 +/- 0.27) mmol/L, P=0.005], and the level of alkaline phosphatase (AKP) in HMF group at discharge was higher than in PF group [(363.98 +/- 122.49) mmol/L vs. (299.73 +/- 117.39) mmol/L, P=0.004]; (5) the incidence of the feeding intolerance (6.5% vs. 18.3%, P=0.04) and sepsis (4.8% vs. 16.7%, P=0.03) in HMF group were less than in PF group, there were no significant differences between the two groups on the morbidity of necrotizing enterocditis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD) (P>0.05). CONCLUSION: HMF for premature infants may ensure the same growth pattern as those fed by premature formula, promote the calcium absorption, decrease the incidence of sepsis and feeding intolerance, and does not increase the incidence of necrotizing enterocolitis. PMID- 26885926 TI - [Endovascular treatment in cerebral artery tandem lesions]. AB - OBJECTIVE: To evaluate the effectiveness and safety of endovascular treatment in solving symptomatic cerebral artery tandem lesions. METHODS: From June 2012 to February 2014, 12 cases (24 lesions) with symptomatic cerebral artery tandem lesions were accepted for the endovascular treatment. The distributions of the tandem lesions were as follows: the common carotid artery and internal carotid artery (1 case), the internal carotid artery and the proximal of the carotid cavernous sinus segment (3 cases), the internal carotid artery and the distal of the carotid cavernous sinus segment (4 cases), the intracranial segment of internal carotid artery and middle cerebral artery M1 segment (2 cases), the first segment of vertebral artery and intracranial segment of vertebral artery (2 cases). All of these cases were treated from distal lesions to proximal lesions except for tandem lesions in the internal carotid artery and the distal of the carotid cavernous sinus segment in order to obtain better support. Tandem lesions were treated in the same operation with local anesthesia or general anesthesia. The procedures of the 12 cases retrospectively were analyzed and the peri operation complications and responsibility region recurrent ischemic stroke incidents observed. RESULTS: All tandem lesions were solved successfully all at once. There were no peri-operation complications or recurrent ischemic stroke incidents. There were no recurrent ischemic stroke incidents or stent restenosis cases in the follow-up. CONCLUSION: It is safe and effective for selective endovascular treatment in solving symptomatic cerebral artery tandem lesions at the same time, but we should take careful preoperative evaluation and improve the operation plan. PMID- 26885927 TI - [Keap1-tat peptide attenuates oxidative stress damage in hippocampal CA1 region and learning and memory deficits following global cerebral ischemia]. AB - OBJECTIVE: To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron, as well as the effect on spacial learning and memory function following global cerebral ischemia. METHODS: Adult male Sprague Dawley (SD) rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 15 min and randomly divided into five groups: sham, sham+Keap1-tat, ischemia/reperfusion (I/R), Keap1-tat peptide- and vehicle-administrated groups. For Keap1-tat or vehicle groups, the rats were treated with Keap1-tat (30, 50, 100 MUg in 5 MUL 0.9% saline) or the same volume vehicle by intracerebroventricular injection (icv) 30 min prior to ischemia. Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region. The spatial learning and memory function of the rats was evaluated using Morris water maze. RESULTS: Compared with sham group, the number of surviving neurons in ischemia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P<0.05), while administration of Keap1-tat significantly decreased the damage following GCI (P<0.05), and the dose of 50 MUg existed the most effective neuroprotective role. Furthermore, immunostaining intensity of 4 HNE and 8-OHdG, markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region. Of significant interest, the time of finding underwater platform in Keap1-tat group animals was significantly short, and after removing the platform, the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehicle and I/R group animals (P<0.05). CONCLUSION: Keap1-tat peptide can effectively attenuate neuronal damage in hippocampal CA1 region and improve learning and memory function, which might bedue to the attenuation of oxidative stress caused by GCI. PMID- 26885929 TI - [Sonographic fingdings of pectoralis major and its tears]. AB - OBJECTIVE: To investigate the normal sonographic anatomic characteristics of the pectoralis major and the clinical value of ultrasound in diagnosing the extent and location of the pectoralis major tears. METHODS: High frequency transducer was used in scanning the pectoralis major. The ultrasonographic images of 40 normal pectoralis major were obtained from 20 healthy volunteers with both sides. Longitudinal and transversal views were performed and stored. The distal tendon was identified in the transverse plane coursing superficially to the long head of the biceps brachii tendon inferior to the level of the subscapularis tendon. Eighteen cases of pectoralis major tears were analyzed retrospectively,with MRI, surgical and ultrasound follow -up RESULTS correlation respectively. RESULTS: High-frequency ultrasound could clearly show the anatomic orientation of the normal pectoralis major. The fibers converge was like a fan into three laminae that twisted upon each other at 90 degrees before coalescing into a single tendon of insertion. In the study, 18 patients of pectoralis major muscle tears [average age: (37.2 +/- 15.6) years] sustained injuries during weightlifting, basketball and impact. Three of the eighteen patients had MRI results; nine had surgical correlation; six were followed by ultrasound. Eleven were injured on the left side, and 7 on the right side. Seven were involved in the distal tendon (1 in sternal head, 2 in clavicular head, 4 in both sternal and clavicular head), five were involved the musculotendinous junction, 6 were involved muscle belly. Twelve cases were partial-thickness petoralis major tears (4 in the distal tendon, four in the muscle tendon junction,4 in the muscle belly),with the partial fiber intact, echogenicity decreased and the internal structure disordered; 6 cases (3 in the distal tendon, 1 in the muscle tendon junction, 2 in pectoralis major muscle belly) were completely disrupted, with fiber fracture and retraction, accompanied with or without hematoma formation. CONCLUSION: High frequency ultrasound can clearly show the anatomic structure of the pectoralis major. Ultrasonography can diagnose the pectoralis major tears with the extent and location of injuries,and can be used to help the clinical treatment. PMID- 26885928 TI - [Percutaneous transluminal angioplasty versus stent implantation for treatment of femoral and popliteal artery lesion resulted from arteriosclerosis obliterans]. AB - OBJECTIVE: To study the clinical effects of percutaneous transluminal angioplasty (PTA) versus stent implantation (ST) after PTA for the treatment of femoral and popliteal artery lesion resulted from arteriosclerosis obliterans. METHODS: One hundred and three patients (119 limbs) treated for femoral and popliteal artery lesion resulted from arteriosclerosis obliterans for ten years were reviewed, of whom 60 limbs were treated by PTA and the other 47 by PTA combined with stent implantation. RESULTS: Among the 60 limbs of the PTA group, there were 22 limbs involved only in femoral and popliteal artery; 13 limbs combined with iliac artery lesion; 17 limbs combined with infrapopliteal artery lesion; 8 limbs combined with iliac and infrapopliteal artery lesion. Among the 47 limbs of the ST group, there were 18 limbs involved only in femoral and popliteal artery; 8 limbs combined with iliac artery lesion; 15 limbs combined with infrapopliteal artery lesion; 6 limbs combined with iliac and infrapopliteal artery lesion. There was no significant difference between the two groups on age, sex, concomitant disease, ankle brachial index(ABI) before treatment and Rutherford classification (P>0.05). The patients' Trans-atlantic inter-society consensus (TASC) C/D was lower in the PTA group than that in the ST group (58.3% vs.76.6%, P=0.047).The follow-up periods were 48.0 (5.0,108.0) and 40.0 (3.0,96.0) months respectively (P=0.064). Compared with the PTA group, the ST group had a better short-term total effective rate (93.6% vs.80.0%, P=0.044) and a higher cost [(33 882.7 +/- 8 695.6) yuan vs. (17 754.8 +/- 3 654.2) yuan, P<0.001]. The short-term marked effective rate of the ST group was higher than that of the PTA group, but the difference was not significant (31.9% vs.21.7%, P=0.231). There was no significant difference between the two groups on short-term efficiency, and complication rates (58.3% vs. 58.3%, P=0.724; 1.7% vs.2.1%, P=1.000). There was no death during perioperative period and no short-term deterioration in both the groups. The long-term marked effective rate was lower and the deterioration rate was higher in the ST group than that in the PTA group, but the difference was not significant (8.5% vs. 15.0%, P=0.381; 14.9% vs. 5.0%, P=0.081).There was no significant difference between the two group on long term total effective rate,accumulative limb salvage rate and reoperation rate (66.0% vs. 66.7%, P=0.939; 94.7% vs. 94.1%, P=0.884; 31.9% vs. 31.7%, P=1.000), and the 1 to 10 years primary and secondary patency rates were similar (P=0.837, P=0.622).When compared based on TASC classification, TASC A/B patients in the ST group had a higher short-term marked effective rate, a higher short-term total effective rate and a higher long-term deterioration rate than those in the PTA group, but the difference was not significant (36.4% vs. 24.0%, P=0.353; 100.0% vs. 88.0%, P=0.322; 18.2% vs. 4.0%, P=0.216). TASC C/D patients had a similar result (30.6% vs. 20.0%, P=0.307; 91.7% vs. 74.3%, P=0.050; 13.9% vs. 5.7%, P=0.226). Both TASC A/B and TASC C/D patients in the ST group had a similar accumulative limb salvage rate with that in the PTA group (90.9% vs. 90.6%, P=0.920; 97.1% vs. 94.1%, P=0.796). CONCLUSION: Stent implantation can increase the cost and short term effective rate at the same time and is not superior to PTA on the long term effective rate and limb salvage rate for femoral and popliteal artery lesion resulted from arteriosclerosis obliterans. PMID- 26885930 TI - [Establishing a luciferase reporter system to evaluate osteogenic differentiation potential of human adipose-derived stem cells]. AB - OBJECTIVE: Human adipose-derived stem cells (hASCs) are a highly attractive source in bone tissue engineering. To generate a luciferase reporter system that could be used to quantitatively and rapidly examine osteogenic differentiation potential of human adipose-derived stem cells (hASCs) in vitro, and eventually make it possible to monitor the osteogenic differentiation of transplanted cells in vivo. METHODS: The genomic DNA harboring promotor regions of osteocalcin and DNA sequences encoding luciferase genes were amplified by PCR and cloned into the pLVX-pTRE-puro vector to generate the OC(pro)-Luc-Puro construct. Then, the OC(pro)-Luc-Puro construct together with three assistant vectors: pMDLg/pRRE, pRSV-REV, and pVSVG, were transiently transfected into HEK293T cells followed by viral supernatants collection, filtration and concentration. Next, the hASCs stably expressing luciferase reporter gene driven by osteocalcin promotor were created with the lentivirus carrying OC(pro)-Luc-Puro cassette under puromycin selection. The OC(pro)-Luc-hASCs were then cultured in the absence or presence of osteogenic differentiation medium. On the 7th and 14th days, after osteogenic induction, cellular extracts were collected and analyzed by luciferase reporter assay. Meanwhile, alizarin red staining and quantification as well as quantitative reverse transcription PCR (qRT-PCR) analysis of osteogenic associated genes osteocalcin (OC), runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP) were used to assess the osteogenic differentiation ability of OC(pro)-Luc-hASCs. RESULTS: OC(pro)-Luc-Puro plasmid and OCpro-Luc hASCs were successfully generated. On the 7th and 14th days after osteogenic induction, the luciferase activity of the cellular extracts from OC(pro)-Luc hASCs was dramatically increased. Consistently, the extracellular matrix mineralization, as shown by Alizarin red S (ARS) staining and quantification was also markedly intensified and a marked increase of the mRNA expression levels of OC, Runx2 and ALP, although to variable extent, was observed upon osteogenic differentiation. These results indicated that the observations from traditional experiments examining hASCs osteogenic differentiation were largely in agreement with that of our luciferase reporter assay in OC(pro)-Luc-hASCs. CONCLUSION: We established a luciferase reporter system that could be used to rapidly, quantitatively and specifically determine osteogenic differentiation ability of hASCs. Comparing with the traditional time-consuming methods, the system we generated here was highly effective. This system not only can be used to examine ostogenic differentiation of hASCs in a high throughput manner, but also provides a way to monitor ostogenic differentiation of cells in vivo. PMID- 26885931 TI - [A novel technique to preserve the alveolar ridge width following tooth extraction in the maxillary frontal area]. AB - OBJECTIVE: To introduce a novel ridge preservation technique with micro-titanium plate avoiding the use of bone grafting materials, and evaluate the potential horizontal bone preservation effect of this new technique, applied on single maxillary central incisors after tooth extraction for future implant restoration. METHODS: Nine patients (six women and three men), mean age (26.0 +/- 5.7) years(from 18 to 34 years) referred to the Department of Oral Implantology, Peking University School and Hospital of Stomotology, were selected and diagnosed with unsalvageable single middle incisor with fine general conditions, no signs of acute local inflammation, no ongoing or previous periodontitis, healthy neighboring teeth and intact buccal bone walls. Tooth extraction, delayed implant placement and implant-supported single crown restoration were selected as treatment plan. The teeth were extracted atraumatically with local anesthesia, followed by a reflection of a minor flap to exposed 2-3 mm of the buccal bone plate. After that, a micro-titanium plate was trimmed and bended to fit the convexity of the labial bone and fixed by two mini pins with intent to support the labial soft tissue. The flap was then repositioned over the micro titanium plate and secured with two single sutures. No bone grafting materials or releasing incisions were needed. The sockets were left to heal without any intention of primary wound closure. Cone-beam computed tomographic (CBCT) scans were obtained before and four months after tooth extraction. Horizontal ridge widths were measured with CBCT software, and the preservation effects were calculated and recorded by the percentage of horizontal ridge alteration. RESULTS: The nine extraction sockets were healed uneventfully. The average socket width before extraction was (7.51 +/- 0.48) mm (6.92-7.82 mm). The average alveolar ridge labial-palatal width at the control point of the edentulous area was (6.81+/-0.44) mm (6.04-7.38 mm) 4 months after tooth extraction, the mean percentage of ridge width preserved was 90.87% +/- 2.91% (87.28%-95.60%). CONCLUSION: This novel ridge preservation method by the usage of a micro-titanium plate did not interfere with the natural socket healing process, and at the same time, largely preserved the width of alveolar ridge without any bone grafting procedures. Long term results remain to be seen. PMID- 26885933 TI - [Pharmaceutical care for a patient with warfarin-induced autoimmune hepatitis]. AB - Here we reported a patient with warfarin-induced autoimmune hepatitis (AIH), and explored new concerns for the pharmaceutical care of warfarin. A 57- year-old woman was admitted to hospital for repeated anorexia, abdominal pain and abnormal liver function. She received prosthetic heart valve replacement because of rheumatic heart disease, and had started warfarin medication since 2 years before. Her liver function was elevated with highest alanine aminotransferase 861 U/L, aspertate aminotransferase 604 U/L, and total bilirubin 106.7 MUmol/L. Her anticoagulant therapy was switched to low molecular weight heparin and the liver function returned to normal. The liver function was elevated when she started to take warfarin again. The patient was then on liver protection therapy, and warfarin was stopped again for the liver biopsy for diagnosis reason. Through medication consultation and evaluation, pharmacists were invited to work together with the physicians and helped to differentiate the reason for abnormal liver function, and provided therapeutic suggestions. Also the pharmacists gained experiences in the treatment of AIH, and discovered a new and severe adverse drug reaction for warfarin. In treating this case, the pharmacists'active involvement into the treatment and evaluation of the effect on the patient reflected the advantage and importance of the multidisciplinary cooperation for pharmacists and physicians when complex diseases are faced. PMID- 26885932 TI - [Anorexia with sinus bradycardia: a case report]. AB - As anorexia patients always go to the psychiatric clinic, little is concerned about the occurrence of sinus bradycardia in these patients for cardiologists and psychiatrists. The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia, and the feature analysis, differential diagnosis and therapeutic principles of this type of sinus bradycardia. We report a case of sinus bradycardia in an anorexia patient with the clinical manifestations, laboratory exams, auxiliary exams, therapeutic methods, and her prognosis, who was admitted to Peking University Third Hospital recently. The patient was a 19 year-old female, who had the manifestation of anorexia. She lost obvious weight in a short time (about 15 kg in 6 months), and her body mass index was 14.8 kg/m(2). The patient felt apparent palpitation, chest depression and short breath, without dizziness, amaurosis or unconsciousness. Vitals on presentation were notable for hypotension, and bradycardia. The initial exam was significant for emaciation, but without lethargy or lower extremity edema. The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute. The laboratory work -up revealed her normal blood routine, electrolytes and liver function. But in her thyroid function test, the free thyroid (FT) hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L (8.9-18.0 ng/L), which were all lower; yet the thyroid stimulating hormone (TSH) was normal 1.48 IU/mL (0.55-4.78 IU/mL). Ultrasound revealed her normal thyroid. Anorexia is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia patients who lose weight apparently in short time enhance the excitability of the parasympathetic nerve, and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia, and functional abnormalities of multiple systems such as hypothyroidism. But this kind of sinus bradycardia and hypothyroidism have good prognosis. And asymptomatic sinus bradycardia with reversible causes, because of the great prognosis, they do not need special treatment. Multiple medical and psychiatric disciplines were consulted, and then, family care, nutritional support and psychiatric therapy were given, and she did not need thyroid hormone replacement therapy. The patient's overall clinical status improved gradually during her hospital stay and her heart rate was recovered to 55 beats per minute. PMID- 26885934 TI - Self-Monitoring Using Continuous Glucose Monitors with Real-Time Feedback Improves Exercise Adherence in Individuals with Impaired Blood Glucose: A Pilot Study. AB - BACKGROUND: Exercise helps individuals with prediabetes or type 2 diabetes (T2D) manage their blood glucose (BG); however, exercise adherence in this population is dismal. In this pilot study we tested the efficacy of a self-monitoring group based intervention using continuous glucose monitors (CGMs) at increasing exercise adherence in individuals with impaired BG. MATERIALS AND METHODS: Thirteen participants with prediabetes or T2D were randomized to an 8-week standard care exercise program (CON condition) (n = 7) or self-monitoring exercise intervention (SM condition) (n = 6). Participants in the SM condition were taught how to self-monitor their exercise and BG, to goal set, and to use CGM to observe how exercise influences BG. We hypothesized that compared with the CON condition, using a real-time CGM would facilitate self-monitoring behavior, resulting in increased exercise adherence. RESULTS: Repeated-measures analysis of variance revealed significant Condition * Time interactions for self-monitoring (P < 0.01), goal setting (P = 0.01), and self-efficacy to self-monitor (P = 0.01), such that the SM condition showed greater increases in these outcomes immediately after the program and at the 1-month follow-up compared with the CON condition. The SM condition had higher program attendance rates (P = 0.03), and a greater proportion of participants reregistered for additional exercise programs (P = 0.048) compared with the CON condition. Participants in both conditions experienced improvements in health-related quality of life, waist circumference, and fitness (P values <0.05). CONCLUSIONS: These findings provide promising initial support for the use of a real-time CGM to foster self-monitoring and exercise behavior in individuals living with prediabetes or T2D. PMID- 26885935 TI - Exometabolomics Assisted Design and Validation of Synthetic Obligate Mutualism. AB - Synthetic microbial ecology has the potential to enhance the productivity and resiliency of biotechnology processes compared to approaches using single isolates. Engineering microbial consortia is challenging; however, one approach that has attracted significant attention is the creation of synthetic obligate mutualism using auxotrophic mutants that depend on each other for exchange or cross-feeding of metabolites. Here, we describe the integration of mutant library fitness profiling with mass spectrometry based exometabolomics as a method for constructing synthetic mutualism based on cross-feeding. Two industrially important species lacking known ecological interactions, Zymomonas mobilis and Escherichia coli, were selected as the test species. Amino acid exometabolites identified in the spent medium of Z. mobilis were used to select three corresponding E. coli auxotrophs (proA, pheA and IlvA), as potential E. coli counterparts for the coculture. A pooled mutant fitness assay with a Z. mobilis transposon mutant library was used to identify mutants with improved growth in the presence of E. coli. An auxotroph mutant in a gene (ZMO0748) with sequence similarity to cysteine synthase A (cysK), was selected as the Z. mobilis counterpart for the coculture. Exometabolomic analysis of spent E. coli medium identified glutathione related metabolites as potentially available for rescue of the Z. mobilis cysteine synthase mutant. Three sets of cocultures between the Z. mobilis auxotroph and each of the three E. coli auxotrophs were monitored by optical density for growth and analyzed by flow cytometry to confirm high cell counts for each species. Taken together, our methods provide a technological framework for creating synthetic mutualisms combining existing screening based methods and exometabolomics for both the selection of obligate mutualism partners and elucidation of metabolites involved in auxotroph rescue. PMID- 26885936 TI - Response to Dr. Parkinson. PMID- 26885937 TI - Sliding Fibers: Slidable, Injectable, and Gel-like Electrospun Nanofibers as Versatile Cell Carriers. AB - Designing biomaterial systems that can mimic fibrous, natural extracellular matrix is crucial for enhancing the efficacy of various therapeutic tools. Herein, a smart technology of three-dimensional electrospun fibers that can be injected in a minimally invasive manner was developed. Open surgery is currently the only route of administration of conventional electrospun fibers into the body. Coordinating electrospun fibers with a lubricating hydrogel produced fibrous constructs referred to as slidable, injectable, and gel-like (SLIDING) fibers. These SLIDING fibers could pass smoothly through a catheter and fill any cavity while maintaining their fibrous morphology. Their injectable features were derived from their distinctive rheological characteristics, which were presumably caused by the combinatorial effects of mobile electrospun fibers and lubricating hydrogels. The resulting injectable fibers fostered a highly favorable environment for human neural stem cell (hNSC) proliferation and neurosphere formation within the fibrous structures without compromising hNSC viability. SLIDING fibers demonstrated superior performance as cell carriers in animal stroke models subjected to the middle cerebral artery occlusion (MCAO) stroke model. In this model, SLIDING fiber application extended the survival rate of administered hNSCs by blocking microglial infiltration at the early, acute inflammatory stage. The development of SLIDING fibers will increase the clinical significance of fiber-based scaffolds in many biomedical fields and will broaden their applicability. PMID- 26885938 TI - Involving lay community researchers in epidemiological research: experiences from a seroprevalence study among sub-Saharan African migrants. AB - Community-based participatory research (CBPR) has received considerable attention during past decades as a method to increase community ownership in research and prevention. We discuss its application to epidemiological research using the case of second-generation surveillance conducted among sub-Saharan African (SSA) migrants in Antwerp city. To inform evidence-based prevention planning for this target group, this HIV-prevalence study used two-stage time-location sampling preceded by formative research. Extensive collaborative partnerships were built with community organizations, a Community Advisory Board provided input throughout the project, and community researchers were trained to participate in all phases of the seroprevalence study. Valid oral fluid samples for HIV testing were collected among 717 SSA migrants and linked to behavioural data assessed through an anonymous survey between December 2013 and August 2014. A qualitative content analysis of various data sources (extensive field notes, minutes of intervision, and training protocols) collected at 77 data collection visits in 51 settings was carried out to describe experiences with challenges and opportunities inherent to the CBPR approach at three crucial stages of the research process: building collaborative partnerships; implementing the study; dissemination of findings including prevention planning. The results show that CBPR is feasible in conducting scientifically sound epidemiological research, but certain requirements need to be in place. These include among others sufficient resources to train, coordinate, and supervise community researchers; continuity in the implementation; transparency about decision-taking and administrative procedures, and willingness to share power and control over the full research process. CBPR contributed to empowering community researchers on a personal level, and to create greater HIV prevention demand in the SSA communities. PMID- 26885939 TI - Three-Dimensional Network of Cation-Cation-Bound Neptunyl(V) Squares: Synthesis and in Situ Raman Spectroscopy Studies. AB - Cation-cation interactions (CCIs) are an essential feature of actinyl chemistry, particularly neptunyl(V). To better understand the formation mechanisms of CCIs, the crystallization process of Np(V) CCI compounds has been explored during the evaporation of acidic Np(V) stock solutions using X-ray diffraction and both ex situ and in situ Raman spectroscopy. At least four Np solid products have been isolated from evaporation of the same Np(V) acidic solution. In situ evaporation using a continuous wave laser (532 nm) as a local heat source produced similar solid products to ex situ experiments with matching Raman signatures. The formation of these products is highly dependent on the evaporation conditions. Slower evaporation appears to favor the formation of a new neptunyl(V) compound, (NpO2)Cl(H2O)2 (1), over other solid products. The structure of 1 features a three-dimensional network of NpO2(+) cations, where neighboring Np(V) ions are only connected to each other through CCIs in a square arrangement. The O?Np?O stretching region shows similar Raman bands in both the solids and solution suggesting that CCIs between Np(V) cations exist prior to crystallization. These results provide new insight into the formation mechanism of Np(V) CCI compounds from solutions. PMID- 26885940 TI - Melt-Quenched Glasses of Metal-Organic Frameworks. AB - Crystalline solids dominate the field of metal-organic frameworks (MOFs), with access to the liquid and glass states of matter usually prohibited by relatively low temperatures of thermal decomposition. In this work, we give due consideration to framework chemistry and topology to expand the phenomenon of the melting of 3D MOFs, linking crystal chemistry to framework melting temperature and kinetic fragility of the glass-forming liquids. Here we show that melting temperatures can be lowered by altering the chemistry of the crystalline MOF state, which provides a route to facilitate the melting of other MOFs. The glasses formed upon vitrification are chemically and structurally distinct from the three other existing categories of melt-quenched glasses (inorganic nonmetallic, organic, and metallic), and retain the basic metal-ligand connectivity of crystalline MOFs, which connects their mechanical properties to their starting chemical composition. The transfer of functionality from crystal to glass points toward new routes to tunable, functional hybrid glasses. PMID- 26885941 TI - Influence of Surface Morphology on the Shear-Induced Wear of Alkylsilane Monolayers: Molecular Dynamics Study. AB - Chemisorbed alkylsilane monolayer coatings have been shown to possess favorable lubrication properties; however, film degradation prevents the widespread use of these materials as lubricants in micro- and nanoelectromechanical systems (MEMS/NEMS). In this work, molecular dynamics (MD) simulations are used to provide insight into the conditions that promote the degradation and wear of these materials. This is achieved through removal of interfacial chain-substrate bonds during shear and the examination of the mobility of the resulting free, unbound chains. Specific focus is given to the effects of surface morphology, which has been shown previously to strongly influence frictional forces in monolayer systems. In-plane order of chain attachments is shown to lead to pressure-induced orientational ordering of monolayers, promoting film stability. This behavior is lost as nonideality is introduced into the substrate and chain patterning on the surface becomes disordered. The presence of surface roughness is found to reduce film stability, with localization of wear observed for chain attachment sites nearest the interface of contact. The influence of substrate nonideality on monolayer degradation is shown to diminish as chain length is increased. PMID- 26885942 TI - Development of an Integrated Theory of Surgical Recovery in Older Adults. AB - Experts argue the health care system is not prepared to meet the unique needs of older surgical patients, including how to provide the best care during the recovery phase. Nutrition plays a critical role in the recovery of surgical patients. Since older adults are at risk for malnutrition, examining the role of nutrition as a mediator for surgical recovery across the care continuum in older adults is critical. Presently there is a paucity of frameworks, models, and guidelines that integrate the role of nutrition on the trajectory of postoperative recovery in older surgical patients. The purpose of this article is to introduce the Integrated Theory of Surgical Recovery in Older Adults, an interdisciplinary middle-range theory, so that scholars, researchers, and clinicians can use this framework to promote recovery from surgery in older adults by considering the contribution of mediators of recovery (nutritional status, functional status, and frailty) unique to the older adults. PMID- 26885943 TI - Comparison of Intake of Animal and Plant Foods and Related Nutrients in Postmenopausal Breast Cancer Survivors and Controls. AB - This study's objective is to assess differences in dietary intakes in breast cancer survivors (n = 13) and women without a history of breast cancer (controls, n = 71). In a cross-sectional design, intake of foods, food groups, nutrients, and non-nutritive sweeteners was assessed using participant-completed three-day food records. All women were postmenopausal (mean age (SD) 58.5 (+/-3.8) y, 95% White, 2.4% Asian Pacific, and 2.4% Black). The two groups did not differ in age, energy intake, or body mass index (p > 0.05). Compared to controls, survivors consumed less dairy products, animal protein, total protein, and calcium, but more legumes, noncitrus fruit, and carbohydrates (p <= 0.05). Calcium intakes were of particular concern in survivors who consumed an average of 686 mg calcium/d, which is <60% of the recommended 1200 mg/d. Given the important role of calcium in bone health and protein in muscle function among aging women, breast cancer survivors may benefit from consultation with a Registered Dietitian or other health professional knowledgeable in nutritional recommendations for postmenopausal breast cancer survivors. PMID- 26885944 TI - Food Insecurity and Eating Behavior Relationships Among Congregate Meal Participants in Georgia. AB - This study explored relationships of food insecurity with cognitive restraint, uncontrolled eating, and emotional eating behaviors among congregate meal participants in northeast Georgia [n = 118 years, age 60 years and older, mean (SD) age = 75 ( 8 ) years, 75% female, 43% Black, 53% obese (Body Mass Index >= 30)]. Food insecurity was assessed with a 6-item questionnaire. Scores ranged from 0 to 6 and were defined as high or marginal food security, FS, 0-1 (70%); low food security, LFS, 2-4 (20%); very low food security, VLFS, 5-6 (10%); and low and very low food security, LVLFS, 2-6 (30%). Eating behavior was assessed with an 18-item Three-Factor Eating Questionnaire R-18. In bivariate analyses food insecurity was consistently associated with cognitive restraint scores above the median split and to a lesser extent with uncontrolled eating scores (p <= 0.05). No association was found between emotional eating and food insecurity. In multivariate linear and logistic regression analyses, food insecurity was consistently associated with cognitive restraint (p <= 0.05) even when controlled for potential confounders (demographics, Body Mass Index, and chronic diseases). Food insecurity was also associated with uncontrolled eating (p <= 0.05), but the relationship was attenuated when controlled for potential confounding variables. Although cognitive restraint is defined as the conscious restriction of food intake to control body weight or promote weight loss, these findings suggest there may be other dimensions of cognitive restraint to consider in nutritional assessment and interventions among food-insecure older adults. PMID- 26885945 TI - Nutritional Risk is Associated with Chronic Musculoskeletal Pain in Community dwelling Older Persons: The PAINEL Study. AB - Malnutrition is a risk factor for noncommunicable diseases related to ageing, and it can also contribute to musculoskeletal health. This study investigated whether nutritional risk is associated with chronic musculoskeletal pain in community dwelling older persons. Nutritional risk was assessed by the DETERMINE Checklist. Chronic musculoskeletal pain was defined as the presence of pain in the past six months that did not disappear for at least 30 consecutive days. Multivariate logistic regression including confounding variables was used for the analysis. The sample was comprised of 383 participants (age 75.6 +/- SD 6.1); the majority were at moderate-to-high nutritional risk (69%) and approximately one third presented chronic musculoskeletal pain (30%). The nutritional risk score was independently associated with chronic musculoskeletal pain: adding one unit in the risk score produces an 11% increment in the odds of presenting pain (OR 1.109, 95% CI 1.022-1.204). Individuals classified into moderate- or high-risk categories also had substantially higher odds (~90%) of presenting chronic musculoskeletal pain when compared to those in the low-risk category, although our findings were only marginally significant. This is the first study to demonstrate the association between nutritional risk and chronic musculoskeletal pain above and beyond the contributed effects from relevant confounders. PMID- 26885947 TI - Quality Analysis of DNA from Cord Blood Buffy Coat: The Best Neonatal DNA Source for Epidemiological Studies? AB - BACKGROUND: Umbilical cord blood is an economical and easy to obtain source of high-quality neonatal genomic DNA. However, although large numbers of cord blood samples have been collected, information on the yield and quality of the DNA extracted from cord blood is scarce. Moreover, considerable doubt still exists on the utility of the buffy coat instead of whole blood as a DNA source. METHODS: We compared the sample storage and DNA extraction costs for whole blood, buffy coat, and all-cell pellet. We evaluated three different DNA purification kits and selected the most suitable one to purify 1011 buffy coat samples. We determined the DNA yield and optical density (OD) ratios and analyzed 48 single-nucleotide polymorphisms using time-of-flight mass spectrometry (TOF MS). We also analyzed eight possible preanalytical variables that may correlate with DNA yield or quality. RESULTS: Buffy coat was the most economical and least labor-intensive source for sample storage and DNA extraction. The average yield of genomic DNA from 200 MUL of buffy coat sample was 16.01 +/- 8.00 MUg, which is sufficient for analytic experiments. The mean A260/A280 ratio and the mean A260/A230 ratio were 1.89 +/- 0.09 and 1.95 +/- 0.66, respectively. More than 99.5% of DNA samples passed the TOF MS test. Only hemolysis showed a strong correlation with OD ratios of DNA, but not with yield. CONCLUSION: Our findings show that cord blood buffy coat yields high-quality DNA in sufficient quantities to meet the requirements of experiments. Buffy coat was also found to be the most economic, efficient, and stable source of genomic DNA. PMID- 26885946 TI - Managing Malnutrition in Older Persons Residing in Care Homes: Nutritional and Clinical Outcomes Following a Screening and Intervention Program. AB - This study aimed to establish prevalence of malnutrition in older adult care home residents and investigate whether a nutritional screening and intervention program could improve nutritional and clinical outcomes. A community-based cohort study was conducted in five Newcastle care homes. 205 participants entered; 175 were followed up. Residents already taking oral nutritional supplements (ONS) were excluded from interventions. Those with Malnutrition Universal Screening Tool (MUST) score of 1 received dietetic advice and >=2 received dietetic advice and were prescribed ONS (220 ml, 1.5 kcal/ml) twice daily for 12 weeks. Body mass index (BMI), MUST, mini nutritional assessment score (MNA)(r), mid upper arm muscle circumference (MAMC), and Geriatric Depression Scale (GDS) were recorded at baseline and 12 weeks. Malnutrition prevalence was 36.6% +/- 6.6 (95% CI). A higher MUST was associated with greater mortality (p = 0.004). Type of intervention received was significantly associated with change in MUST score (p < 0.001); dietetic advice resulting in the greatest improvement. There were no significant changes in BMI (p = 0.445), MAMC (p = 0.256), or GDS (p = 0.385) following the interventions. Dietitian advice may slow the progression of nutritional decline. In this study oral nutritional supplements over a 3-month period did not significantly improve nutritional status in malnourished care home residents. PMID- 26885948 TI - A Vertically Integrated Junctionless Nanowire Transistor. AB - A vertically integrated junctionless field-effect transistor (VJ-FET), which is composed of vertically stacked multiple silicon nanowires (SiNWs) with a gate-all around (GAA) structure, is demonstrated on a bulk silicon wafer for the first time. The proposed VJ-FET mitigates the issues of variability and fabrication complexity that are encountered in the vertically integrated multi-NW FET (VM FET) based on an identical structure in which the VM-FET, as recently reported, harnesses a source and drain (S/D) junction for its operation and is thus based on the inversion mode. Variability is alleviated by bulk conduction in a junctionless FET (JL-FET), where current flows through the core of the SiNW, whereas it is not mitigated by surface conduction in an inversion mode FET (IM FET), where current flows via the surface of the SiNW. The fabrication complexity is reduced by the inherent JL structure of the JL-FET because S/D formation is not required. In contrast, it is very difficult to dope the S/D when it is positioned at each floor of a tall SiNW with greater uniformity and with less damage to the crystalline structure of the SiNW in a VM-FET. Moreover, when the proposed VJ-FET is used as nonvolatile flash memory, the endurance and retention characteristics are improved due to the above-mentioned bulk conduction. PMID- 26885949 TI - Annual Iron Loss Associated with Hemodialysis. AB - BACKGROUND: In order to keep up the optimal iron status in chronic hemodialysis patients, it is important to know how much iron is lost due to hemodialysis. Residual blood associated with the hemodialysis procedure together with blood sampling inevitably causes the loss of iron in chronic hemodialysis patients. Recent advances in hemodialysis techniques might have reduced this complication. In this cross-sectional study, we directly measured total iron loss by hemodialysis. METHODS: Two hundred thirty-nine patients who received chronic hemodialysis at Otowa Memorial Hospital were enrolled; 65.7% of patients were men, and mean age was 67 +/- 6.4 years (mean +/- SD) and 43.2% were diabetic. Residual blood in blood tubing set and dialyzer after rinse back with saline was collected and homogenized. The iron content including free, protein-bound and heme iron was measured using an atomic absorption spectrometry. RESULTS: The mean iron content in residual blood was 1,247.3 +/- 796.2 ug (mean +/- SD) and the median was 1,002 ug (95% CI 377.6-3,461.6 ug), indicating 160.8 mg (95% CI 58.9 540.0 mg) iron loss annually when hemodialysis was performed 156 times a year. Fifty milliliter whole blood for monthly blood test and another 2 ml of whole blood lost by paracentesis at every dialysis session contains 228.6 and 118.9 mg iron at 11 g/dl hemoglobin, respectively. Therefore, an annual total iron loss due to hemodialysis comes to 508.3 mg (95% CI 406.4-887.5 mg). CONCLUSIONS: Five hundred milligram of annual iron supplementation might be sufficient to maintain iron status in hemodialysis patients, which is less than the dose recommended as 1,000-2,000 mg a year. Further study will be required to verify this iron supplementation dosage with recent hemodialysis procedure. PMID- 26885950 TI - Management of choledochal cysts. AB - PURPOSE OF REVIEW: Historically, surgical treatment of choledochal cyst consisted of cyst enterostomy. However, incomplete cyst excision can result in recurrent symptoms and malignant transformation within the cyst remnant. Accordingly, management of choledochal cyst now includes complete cyst excision whenever possible. We provide a review detailing the up to date management of choledochal cysts. We describe choledochal cyst-type specific surgical approaches, the impact of minimally invasive surgery in choledochal cyst therapy, and long-term sequelae of choledochal cyst management. RECENT FINDINGS: Treatment of choledochal cyst aims to avoid the numerous hepatic, pancreatic, or biliary complications that may occur. More recently, minimally invasive approaches are being used for the treatment of choledochal cyst with acceptable morbidity and mortality. Moreover, long-term follow up of choledochal cyst patients after resection has demonstrated that although the risk of biliary malignancy is significantly decreased after choledochal cyst resection, these patients may remain at a slightly increased risk of biliary malignancy even after excision. SUMMARY: Management of choledochal cyst and the operative conduct will depend upon the patient comorbidities and choledochal cyst subtype. However, given the complex nature of choledochal cyst and limited experience of most centers, these patients should be evaluated and treated at high-volume hepatopancreaticobiliary centers familiar with management of choledochal cyst. PMID- 26885951 TI - Primary biliary cholangitis in China. AB - PURPOSE OF REVIEW: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by immunomediated destruction of small and medium sized intrahepatic bile ducts. In 1987, a cDNA for a 74 kDa mitochondrial autoantigen was cloned and identified as the E2 component of the mitochondrial pyruvate dehydrogenase complex, which improved the diagnosis and changed research directions in this field. In 1958, the first Chinese case of PBC was reported. But until 1990, a comprehensive description of the characteristics of Chinese PBC patients was published. In China we now know that PBC is not rare and usually does not progress to cirrhosis. RECENT FINDINGS: The number of Chinese patients with PBC has increased each and every year. This increase may be associated with the changes of liver disease spectrum, the application of convenient autoantibody detection kits, and the comprehensive understanding of the disease. It may also reflect, however, a westernization change in environmental features with China. There is now significant and important basic and clinical research on PBC in China, with major contributions in diagnostic criteria, treatment, and on basic biology. This has led to exciting proposals based on Chinese PBC cohorts. SUMMARY: Chinese hepatologists and scientists are now focusing their efforts on PBC. These efforts have led to new diagnostic biomarkers, novel therapeutic methods (stem cells and Chinese traditional medicine), and unique immunological mechanisms, including roles for T-follicular helper cells and monocyte subpopulations, both of which are involved in the breach of immune tolerance for PBC. PMID- 26885955 TI - A Public Health of Consequence--March 2016. PMID- 26885956 TI - Shorter Lives and Poorer Health on the Campaign Trail. PMID- 26885957 TI - Butler Responds. PMID- 26885958 TI - 2015-2020 National HIV/AIDS Strategy Goals for HIV Linkage and Retention in Care: Recommendations From Program Implementers. PMID- 26885959 TI - Federal Funding for Kidney Disease Research: A Missed Opportunity. PMID- 26885960 TI - Neighborhoods and Health: What Do We Know? What Should We Do? PMID- 26885961 TI - Evaluating Public Health Interventions: 2. Stepping Up to Routine Public Health Evaluation With the Stepped Wedge Design. AB - In a stepped wedge design (SWD), an intervention is rolled out in a staggered manner over time, in groups of experimental units, so that by the end, all units experience the intervention. For example, in the MaxART study, the date at which to offer universal antiretroviral therapy to otherwise ineligible clients is being randomly assigned in nine "steps" of four months duration so that after three years, all 14 facilities in northern and central Swaziland will be offering early treatment. In the common alternative, the cluster randomized trial (CRT), experimental units are randomly allocated on a single common start date to the interventions to be compared. Often, the SWD is more feasible than the CRT, both for practical and ethical reasons, but takes longer to complete. The SWD permits both within- and between- unit comparisons, while the CRT only allows between unit comparisons. Thus, confounding bias with respect to time-invariant factors tends to be lower in an SWD than a CRT, but the SWD cannot as readily control for confounding by time-varying factors. SWDs have generally more statistical power than CRTs, especially as the intraunit correlation and the number of participants within unit increases. Software for both designs are available, although for a more limited set of SWD scenarios. PMID- 26885962 TI - Coefficient alpha as a Measure of Test Score Reliability: Review of 3 Popular Misconceptions. AB - We discuss 3 popular misconceptions about Cronbach alpha or coefficient alpha, traditionally used in public health and the behavioral sciences as an index of test score reliability. We also review several other indices of test score reliability. We encourage researchers to thoughtfully consider the nature of their data and the options when choosing an index of reliability, and to clearly communicate this choice and its implications to their audiences. PMID- 26885963 TI - Voigt Responds. PMID- 26885964 TI - Renormalization and Regulation of E-Cigarettes. PMID- 26885965 TI - Attitudes of Health Care Providers Toward LGBT Patients: The Need for Cultural Sensitivity Training. PMID- 26885966 TI - Sabin and Riskind Respond. PMID- 26885967 TI - Lin et al. Respond. PMID- 26885971 TI - Active Transportation Surveillance-United States, 1999-2012. PMID- 26885968 TI - Categorization of Frequent Emergency Department Use in an Insured Homeless Population. PMID- 26885972 TI - Molecular separations with breathing metal-organic frameworks: modelling packed bed adsorbers. AB - Various metal-organic framework (MOFs) adsorbents show peculiar adsorption behaviour as they can adopt different crystal phases, each phase with its own adsorption characteristics. Besides external stimuli such as temperature or light, different species of guest adsorbate can trigger a transition (breathing) of the host structure at a different pressure. Such phase transitions also occur during dynamic separations on a packed bed of adsorbent, where the concentrations of the adsorbates vary throughout axial column distance and time. This work presents a general strategy to model the adsorption behavior of such phase changing adsorbents during column separations and focuses on remarkable model predictions for pure components and binary mixtures in diluted and non-diluted conditions. During binary breakthrough experiments, the behaviour of flexible adsorbents is quite complex. A succession of complete or even partial phase transformations (resulting in phase coexistence) can occur during the adsorption process. A variety of unusual breakthrough profiles is observed for diluted binary mixtures. Simulations reveal at least five types of breakthrough profiles to emerge. The occurrence of these cases can be rationalized by the hodograph technique, combined with the phase diagram of the adsorbent. The remarkable experimental breakthrough profiles observed for ortho-xylene/ethylbenzene (diluted) and CO2/CH4 (non-diluted) separation on the flexible MIL-53 framework can be rationalized by application of the proposed model strategy. PMID- 26885974 TI - The Relationship between GRACE Score and Epicardial Fat Thickness in non-STEMI Patients. AB - BACKGROUND: GRACE risk score (GS) is a scoring system which has a prognostic significance in patients with non-ST segment elevation myocardial infarction (non STEMI). OBJECTIVE: The present study aimed to determine whether end-systolic or end-diastolic epicardial fat thickness (EFT) is more closely associated with high risk non-STEMI patients according to the GS. METHODS: We evaluated 207 patients who had non-STEMI beginning from October 2012 to February 2013, and 162 of them were included in the study (115 males, mean age: 66.6 +/- 12.8 years). End systolic and end-diastolic EFTs were measured with echocardiographic methods. Patients with high in-hospital GS were categorized as the H-GS group (in hospital GS > 140), while other patients were categorized as the low-to-moderate risk group (LM-GS). RESULTS: Systolic and diastolic blood pressures of H-GS patients were lower than those of LM-GS patients, and the average heart rate was higher in this group. End-systolic EFT and end-diastolic EFT were significantly higher in the H-GS group. The echocardiographic assessment of right and left ventricles showed significantly decreased ejection fraction in both ventricles in the H-GS group. The highest correlation was found between GS and end-diastolic EFT (r = 0.438). CONCLUSION: End-systolic and end-diastolic EFTs were found to be increased in the H-GS group. However, end-diastolic EFT and GS had better correlation than end-systolic EFT and GS. PMID- 26885975 TI - Unraveling Trichoderma species in the attine ant environment: description of three new taxa. AB - Fungus-growing "attine" ants forage diverse substrates to grow fungi for food. In addition to the mutualistic fungal partner, the colonies of these insects harbor a rich microbiome composed of bacteria, filamentous fungi and yeasts. Previous work reported some Trichoderma species in the fungus gardens of leafcutter ants. However, no studies systematically addressed the putative association of Trichoderma with attine ants, especially in non-leafcutter ants. Here, a total of 62 strains of Trichoderma were analyzed using three molecular markers (ITS, tef1 and rpb2). In addition, 30 out of 62 strains were also morphologically examined. The strains studied correspond to the largest sampling carried out so far for Trichoderma in the attine ant environment. Our results revealed the richness of Trichoderma in this environment, since we found 20 Trichoderma species, including three new taxa described in the present work (Trichoderma attinorum, Trichoderma texanum and Trichoderma longifialidicum spp. nov.) as well as a new phylogenetic taxon (LESF 545). Moreover, we show that all 62 strains grouped within different clades across the Trichoderma phylogeny, which are identical or closely related to strains derived from several other environments. This evidence supports the transient nature of the genus Trichoderma in the attine ant colonies. The discovery of three new species suggests that the dynamic foraging behavior of these insects might be responsible for accumulation of transient fungi into their colonies, which might hold additional fungal taxa still unknown to science. PMID- 26885973 TI - Dyslipidemia is Associated with Unfit and Overweight-Obese Children and Adolescents. AB - BACKGROUND: Both poor aerobic fitness and obesity, separately, are associated with abnormal lipid profiles. OBJECTIVE: To identify possible relationships of dyslipidemia with cardiorespiratory fitness and obesity, evaluated together, in children and adolescents. METHODS: This cross-sectional study included 1,243 children and adolescents (563 males and 680 females) between 7 and 17 years of age from 19 schools. Obesity was assessed using body mass index (BMI) measurements, and cardiorespiratory fitness was determined via a 9-minute run/walk test. To analyze the lipid profile of each subject, the following markers were used: total cholesterol, cholesterol fractions (high-density lipoprotein and low-density lipoprotein) and triglycerides. Data were analyzed using SPSS v. 20.0, via prevalence ratio (PR), using the Poisson regression. RESULTS: Dyslipidemia is more prevalent among unfit/overweight-obese children and adolescents compared with fit/underweight-normal weight boys (PR: 1.25; p = 0.007) and girls (PR: 1.30, p = 0.001). CONCLUSIONS: The prevalence of dyslipidemia is directly related to both obesity and lower levels of cardiorespiratory fitness. PMID- 26885976 TI - Blinded by Beauty: Attractiveness Bias and Accurate Perceptions of Academic Performance. AB - Despite the old adage not to 'judge a book by its cover', facial cues often guide first impressions and these first impressions guide our decisions. Literature suggests there are valid facial cues that assist us in assessing someone's health or intelligence, but such cues are overshadowed by an 'attractiveness halo' whereby desirable attributions are preferentially ascribed to attractive people. The impact of the attractiveness halo effect on perceptions of academic performance in the classroom is concerning as this has shown to influence students' future performance. We investigated the limiting effects of the attractiveness halo on perceptions of actual academic performance in faces of 100 university students. Given the ambiguity and various perspectives on the definition of intelligence and the growing consensus on the importance of conscientiousness over intelligence in predicting actual academic performance, we also investigated whether perceived conscientiousness was a more accurate predictor of academic performance than perceived intelligence. Perceived conscientiousness was found to be a better predictor of actual academic performance when compared to perceived intelligence and perceived academic performance, and accuracy was improved when controlling for the influence of attractiveness on judgments. These findings emphasize the misleading effect of attractiveness on the accuracy of first impressions of competence, which can have serious consequences in areas such as education and hiring. The findings also have implications for future research investigating impression accuracy based on facial stimuli. PMID- 26885977 TI - The High Cost of HIV-Positive Inpatient Care at an Urban Hospital in Johannesburg, South Africa. AB - BACKGROUND: While most HIV care is provided on an outpatient basis, hospitals continue to treat serious HIV-related admissions, which is relatively resource intensive and expensive. This study reports the primary reasons for HIV-related admission at a regional, urban hospital in Johannesburg, South Africa and estimates the associated lengths of stay and costs. METHODS AND FINDINGS: A retrospective cohort study of adult, medical admissions was conducted. Each admission was assigned a reason for admission and an outcome. The length of stay was calculated for all patients (N = 1,041) and for HIV-positive patients (n = 469), actual utilization and associated costs were also estimated. Just under half were known to be HIV-positive admissions. Deaths and transfers were proportionately higher amongst HIV-positive admissions compared to HIV-negative and unknown. The three most common reasons for admission were tuberculosis and other mycobacterial infections (18%, n = 187), cardiovascular disorders (12%, n = 127) and bacterial infections (12%, n = 121). The study sample utilized a total of 7,733 bed days of those, 55% (4,259/7,733) were for HIV-positive patients. The average cost per admission amongst confirmed HIV-positive patients, which was an average of 9.3 days in length, was $1,783 (United States Dollars). CONCLUSIONS: Even in the era of large-scale antiretroviral treatment, inpatient facilities in South Africa shoulder a significant HIV burden. The majority of this burden is related to patients not on ART (298/469, 64%), and accounts for more than half of all inpatient resources. Reducing the costs of inpatient care is thus another important benefit of expanding access to ART, promoting earlier ART initiation, and achieving rates of ART retention and adherence. PMID- 26885978 TI - Endurance Exercise Enhances the Effect of Strength Training on Muscle Fiber Size and Protein Expression of Akt and mTOR. AB - Reports concerning the effect of endurance exercise on the anabolic response to strength training have been contradictory. This study re-investigated this issue, focusing on training effects on indicators of protein synthesis and degradation. Two groups of male subjects performed 7 weeks of resistance exercise alone (R; n = 7) or in combination with preceding endurance exercise, including both continuous and interval cycling (ER; n = 9). Muscle biopsies were taken before and after the training period. Similar increases in leg-press 1 repetition maximum (30%; P<0.05) were observed in both groups, whereas maximal oxygen uptake was elevated (8%; P<0.05) only in the ER group. The ER training enlarged the areas of both type I and type II fibers, whereas the R protocol increased only the type II fibers. The mean fiber area increased by 28% (P<0.05) in the ER group, whereas no significant increase was observed in the R group. Moreover, expression of Akt and mTOR protein was enhanced in the ER group, whereas only the level of mTOR was elevated following R training. Training-induced alterations in the levels of both Akt and mTOR protein were correlated to changes in type I fiber area (r = 0.55-0.61, P<0.05), as well as mean fiber area (r = 0.55-0.61, P<0.05), reflecting the important role played by these proteins in connection with muscle hypertrophy. Both training regimes reduced the level of MAFbx protein (P<0.05) and tended to elevate that of MuRF-1. The present findings indicate that the larger hypertrophy observed in the ER group is due more to pronounced stimulation of anabolic rather than inhibition of catabolic processes. PMID- 26885981 TI - Implantable cardioverter defibrillators for primary prevention of sudden death in hypertrophic cardiomyopathy. AB - AIMS: Sudden cardiac death (SCD) may complicate hypertrophic cardiomyopathy (HCM) natural course. Patient selection for implantable cardioverter defibrillator (ICD) therapy in the primary prevention setting is still a challenge. METHODS: Thirty-seven HCM patients with a primary prevention ICD were included. All patients underwent preimplantation SCD risk assessment and semi-annual device interrogation during follow-up. Primary end point was the time to first appropriate ICD intervention including antitachycardia pacing or shock. Inappropriately delivered ICD therapies served as secondary end point. RESULTS: During a median follow-up of 3.1 years, 10 (27%) patients received one or more appropriate ICD therapies. First appropriate ICD intervention rate was 7.2%/year (95% CI: 3.4-13.2) with a 5-year cumulative probability of 29.2 +/- 7.4%. No SCD risk marker was significantly associated with the primary end point, whereas event rates were comparable among patients with one, two or three or more SCD risk markers (log-rank P = 0.58). Patients with a history of SCD in first-degree relatives with HCM were at 3.8 times higher risk of experiencing an ICD intervention compared with those with no family history of SCD (HR: 3.8; 95% CI: 1.0-14.1, P = 0.05). Seven (18.9%) patients experienced one or more inappropriate ICD therapies; beta-blocker therapy was associated with 75% fewer inappropriate ICD interventions (HR: 0.15; 95% CI: 0.03-0.89). CONCLUSION: Current criteria identify a subgroup of patients with HCM at increased risk of major arrhythmic events as indicated by high ICD intervention rates. However, no individual risk marker demonstrated superior predictive ability over the others, whereas simple arithmetic summing of risk markers was not associated with increased ICD intervention rates. PMID- 26885979 TI - Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer. AB - BACKGROUND: miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS). MATERIAL AND METHODS: The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS. RESULTS: A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)). CONCLUSION: The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer. PMID- 26885980 TI - The Tocotrienol-Rich Fraction Is Superior to Tocopherol in Promoting Myogenic Differentiation in the Prevention of Replicative Senescence of Myoblasts. AB - Aging results in a loss of muscle mass and strength. Myoblasts play an important role in maintaining muscle mass through regenerative processes, which are impaired during aging. Vitamin E potentially ameliorates age-related phenotypes. Hence, this study aimed to determine the effects of the tocotrienol-rich fraction (TRF) and alpha-tocopherol (ATF) in protecting myoblasts from replicative senescence and promoting myogenic differentiation. Primary human myoblasts were cultured into young and senescent stages and were then treated with TRF or ATF for 24 h, followed by an analysis of cell proliferation, senescence biomarkers, cellular morphology and differentiation. Our data showed that replicative senescence impaired the normal regenerative processes of myoblasts, resulting in changes in cellular morphology, cell proliferation, senescence-associated beta galactosidase (SA-beta-gal) expression, myogenic differentiation and myogenic regulatory factors (MRFs) expression. Treatment with both TRF and ATF was beneficial to senescent myoblasts in reclaiming the morphology of young cells, improved cell viability and decreased SA-beta-gal expression. However, only TRF treatment increased BrdU incorporation in senescent myoblasts, as well as promoted myogenic differentiation through the modulation of MRFs at the mRNA and protein levels. MYOD1 and MYOG gene expression and myogenin protein expression were modulated in the early phases of myogenic differentiation. In conclusion, the tocotrienol-rich fraction is superior to alpha-tocopherol in ameliorating replicative senescence-related aberration and promoting differentiation via modulation of MRFs expression, indicating vitamin E potential in modulating replicative senescence of myoblasts. PMID- 26885982 TI - Balloon aortic valvuloplasty before noncardiac surgery in severe aortic stenosis: a single-center experience. AB - OBJECTIVES: The aim of this study is to investigate the role and short-term results of balloon aortic valvuloplasty (BAV) before noncardiac surgery in a high selected cohort of patients. BACKGROUND: Aortic stenosis is one of the most common valvular heart diseases and a well recognized risk factor for perioperative mortality. METHODS: Between May 2012 and July 2013 we enrolled 15 consecutive patients with severe aortic stenosis to allow urgent major noncardiac surgery. They had been excluded from surgical aortic valve replacement and transcatheter aortic valve implantation. RESULTS: Fifteen patients underwent BAV as a bridge to noncardiac surgery. They were elderly (mean age 81 +/- 5 years) and predominantly men (66%) with high surgery risk (mean logistic EuroSCORE: 31.1 +/- 18.2%). Three patients underwent vascular surgery, five underwent thoracic surgery, five were subjected to major abdominal surgery and in the last two patients orthopedic surgery and mastectomy were performed. No adverse events were observed in the perioperative period. Six patients (40%) were in New York Heart Association class III or IV. Mean aortic valve area was 0.52 +/- 0.1 cm/m; mean aortic pressure gradient was 55.6 +/- 10.8 mmHg. BAV was performed successfully in all patients. The mean peak-to-peak gradient assessed by catheterization significantly reduced after BAV (from 69.0 +/- 22.1 to 29.7 +/- 9.3 mmHg; P < 0.0001). The echocardiographic mean gradient was also significantly improved (from 55.6 +/- 10.8 to 33.8 +/- 7.9 mmHg; P < 0.0001). Survival at 30 days and at 6 months' follow-up respectively was 100%. At 6 months' follow-up clinical status according to New York Heart Association class was significantly improved (P < 0.0001). CONCLUSION: BAV is well tolerated and effective in high-risk patients with severe aortic stenosis undergoing noncardiac surgery with good short-term survival. It could represent a valid choice of treatment prior to noncardiac surgery in these high-risk patients. PMID- 26885983 TI - The C-terminal cytoplasmic tail of hedgehog receptor Patched1 is a platform for E3 ubiquitin ligase complexes. AB - The Sonic hedgehog (Shh) signaling pathway plays a crucial role in cell proliferation and differentiation via Patched1 (Ptc1), a 12-pass transmembrane receptor protein. The C-terminal cytoplasmic tail of Ptc1 can be cleaved to release the 7th intracellular domain (ICD7), whose function is still unclear. In this study, we found that the ICD7 fragment of Ptc1 associates with polyubiquitinated species. Using mass spectrometry, we identified a cluster of E3 ubiquitin ligase complex as novel Ptc1 ICD7-binding proteins. In particular, Ptc1 ICD7 interacted with most components of the Cullin-2 (CUL2)-based E3 ligase complex, including TCEB1 (EloC), TCEB2 (EloB), ZYG11B, and CUL2 itself. To address the significance of CUL2-based E3 ligase in Ptc1 function, we examined the effects of CUL2 knockdown on Shh-induced osteoblast differentiation in the mesenchymal stem cell line C3H10T1/2. Indeed, knockdown of CUL2 abolished the Shh induced stem cell differentiation. These results suggest that CUL2-based E3 ligase complex may play a role in Shh- and Ptc1-dependent signaling pathways. PMID- 26885985 TI - Community-based tsetse fly control significantly reduces fly density and trypanosomosis prevalence in Metekel Zone, Northwest, Ethiopia. AB - African animal trypanosomosis is a great obstacle to livestock production where tsetse flies play a major role. Metekel zone is among the tsetse-infested areas. Community-based tsetse fly and trypanosomosis control using targets was conducted from June 2011 to May 2012 in Metekel zone, Ethiopia, to decrease trypanosomosis and tsetse fly. Cloth screen targets were developed, impregnated with 0.1 % deltamethrin, and deployed alongside rivers by the research team together with the community animal health workers. Monthly parasitological and entomological data were collected, processed, and compared with similar data collected before control. Overall average tsetse fly (Glossina tachinoides) density decreased from 1.13 to 0.18 fly/trap/day after control. The density was decreased in all sites with no significant difference among the sites. However, higher decrements were observed in the dry and late dry seasons by more than 12 and 6 times, respectively. The reduction in overall apparent prevalence of trypanosomosis caused by Trypanosoma congolense, Trypanosoma brucei, and Trypanosoma vivax from 12.14 % before to 3.61 % after control coincides with the tsetse fly reduction. In all the study sites, significant reduction was observed before and after control. The highest decrement was observed in the late dry season when the apparent prevalence was reduced from 7.89 to 1.17 % before and after control, respectively. As this approach is simple, cost-effective, and appropriate for riverine tsetse species, we recommend to be scaled up to other similar places. PMID- 26885986 TI - Molasses supplementation for dual-purpose cows during the dry season in subtropical Mexico. AB - The effect of including 9 % of molasses in supplements offered to dual purpose cows, during dry season in subtropical Mexico was determined. Forage availability in pastures during the dry season is reduced and of low quality. Molasses is a readily available source of energy that may improve forage utilization and could have a positive effect on cow's milk production and calves daily weight gain (CDWG). Twelve multiparous Brown Swiss cows (409 +/- 33 kg of body weight and 136 +/- 73 days in milk), and their calves were randomly assigned to two supplements (six cows per treatment). Control supplement (COS) consisted of cracked maize ears (CME), soybean meal and urea (14 % CP), and experimental supplement in which 9 % of CME was replaced by molasses (MOS). Cows received 4.5 kg/cow/day dry matter (DM) of supplement. Experiment lasted 10 weeks divided in five experimental periods (EP). Animal responses (milk yield, milk composition, body weight, body condition score and CDWG) were recorded at the end of every EP. A linear mixed model was used to analyse the data as a complete random design. Net profits from milk and beef due to supplements were estimated using partial budget approach. Average milk yield was 7 (kg/cow/day) with 30.6, 30.4 and 42.5 (g/kg milk) of fat, protein and lactose, respectively. Average cow weight was 422 kg and CDWG was 0.8 kg/day. No significant responses on animal production variables were found when 9 % of MOS was included in the supplement; however, total net income increased on 4 %, due to higher CDWG. PMID- 26885987 TI - Rice gluten meal as an alternative by-product feed for growing dairy calves. AB - This experiment aimed at studying the nutritional characteristics and feeding value of rice gluten meal (RGM, a wet-milling by-product of rice) in growing dairy calves. RGM contained 464 g/kg of crude protein with 821 and 196 g/kg nitrogen (N) of borate-phosphate insoluble N and acid detergent insoluble N, respectively, which were higher (P < 0.05) than groundnut cake (GNC). In vitro gas production, organic matter digestibility and energy values were comparable between RGM and GNC. For in vivo trial, 18 Karan-Fries calves (6-12 months) were randomly assigned into three groups based on comparable body weight and age. The first group (GP-I) was fed concentrate mixture containing mainly GNC as protein source, whilst it was replaced by RGM up to 50 and 75 % on N basis, in second (GP II) and third (GP-III) groups, respectively. Thus, RGM constituted 140 and 210 g/kg of concentrate mixture of GP-II and GP-III, respectively. In addition, all animals were offered chopped green maize and wheat straw for the whole experimental period of 90 days. Results revealed that there was no difference in intake and digestibility of nutrients, N balance, average daily gain (ADG) and feed efficiency among three groups. Nevertheless, RGM-based diets produced cost effective ADG than GP-I. Furthermore, experimental calves did not differ in haematological variables like glucose, blood urea N, plasma proteins and non esterified fatty acids. This study demonstrated that RGM could be incorporated successfully in the concentrate mixture, replacing 75 % of GNC without any discernable compromise in the performance of growing calves. PMID- 26885984 TI - Response of the JAK-STAT pathway to mammalian hibernation in 13-lined ground squirrel striated muscle. AB - Over the course of the torpor-arousal cycle, hibernators must make behavioral, physiological, and molecular rearrangements in order to keep a very low metabolic rate and retain organ viability. 13-lined ground squirrels (Ictidomys tridecemlineatus) remain immobile during hibernation, and although the mechanisms of skeletal muscle survival are largely unknown, studies have shown minimal muscle loss in hibernating organisms. Additionally, the ground squirrel heart undergoes cold-stress, reversible cardiac hypertrophy, and ischemia-reperfusion without experiencing fatal impairment. This study examines the role of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway in the regulation of cell stress in cardiac and skeletal muscles, comparing euthermic and hibernating ground squirrels. Immunoblots showed a fivefold decrease in JAK3 expression during torpor in skeletal muscle, along with increases in STAT3 and 5 phosphorylation and suppressors of cytokine signaling-1 (SOCS1) protein levels. Immunoblots also showed coordinated increases in STAT1, 3 and 5 phosphorylation and STAT1 inhibitor protein expression in cardiac muscle during torpor. PCR analysis revealed that the activation of these pro-survival signaling cascades did not result in coordinate changes in downstream genes such as anti-apoptotic B-cell lymphoma-2 (Bcl-2) family gene expression. Overall, these results indicate activation of the JAK-STAT pathway in both cardiac and skeletal muscles, suggesting a response to cellular stress during hibernation. PMID- 26885988 TI - Rumen microorganisms, methane production, and microbial protein synthesis affected by mangosteen peel powder supplement in lactating dairy cows. AB - Four crossbred dairy cows (50 % Holstein-Friesian * 50 % Thai native), 404 +/- 50.0 kg of body weight (4 years old) and 90 +/- 5 day in milk with daily milk production of 9 +/- 2.0 kg/day, were randomly assigned according to a 4 * 4 Latin square design to study the effect of mangosteen (Garcinia mangostana) peel powder (MSP) supplementation on rumen microorganisms, methane production, and microbial protein synthesis fed concentrate containing yeast fermented cassava chip protein (YEFECAP). The treatments were different levels of MSP supplementation at 0, 100, 200, and 300 g/head/day. Rice straw was used as a roughage source fed ad libitum, and concentrate containing YEFECAP at 200 g/kg concentrate was offered corresponding to concentrate-to-milk-yield ratio at 1:2. A quantitative real-time PCR approach was used to determine the population densities of ruminal microorganisms. The results revealed that supplementation of MSP did not affect on Fibrobactor succinogenes, Ruminococcus flavefaciens, and Ruminococcus albus (P > 0.05). However, total bacteria was linearly increased (P < 0.01) while methanogens and protozoal population were linearly decreased (P < 0.01) with increasing level of MSP supplementation. Increasing level of MSP supplement could decrease rumen methane production from 27.5 to 23.7 mmol/100 ml(3). Furthermore, cows that received MSP at 300 g/head/day had the highest microbial crude protein and efficiency of rumen microbial N synthesis (416.8 g/day and 16.2 g/kg organic matter truly digested in the rumen (OMDR), respectively). In conclusion, supplementation of MSP at 300 g/head/day with YEFECAP as a protein source in the concentrate mixture revealed an enhancement of rumen fermentation and methane reduction in lactating dairy cows. PMID- 26885989 TI - An analysis of neurosurgical practice patterns and outcomes for serious to critical traumatic brain injuries in a mature trauma state. AB - BACKGROUND: We sought to characterize trends in neurosurgical practice patterns and outcomes for serious to critical traumatic brain injuries from 2003 to 2013 in the mature trauma state of Pennsylvania. METHODS: All 2003 to 2013 admissions to Pennsylvania's 30 accredited Level I to II trauma centers with serious to critical traumatic brain injuries (head Abbreviated Injury Scale [AIS] score >= 3, Glasgow Coma Scale [GCS] score < 13) were extracted from the state registry. Adjusted temporal trend tests controlling for demographic and injury severity covariates assessed the impact of admission year on intervention rates (craniotomy, craniectomy, and intracranial pressure monitor/ventriculostomy [ICP]) and outcome measures for the total population as well as serious (head AIS score >= 3; GCS score, 9-12) and critical (head AIS score >= 3, GCS score <= 8) subgroups. RESULTS: A total of 22,229 patients met inclusion criteria. Admission year was significantly associated with an adjusted increase in craniectomy (adjusted odds ratio [AOR], 1.12 [1.09-1.14]; p < 0.001) and ICP rates (AOR, 1.03 [1.02-1.04]; p < 0.001) and a decrease in craniotomy rate (AOR, 0.96 [0.95-0.97]; p < 0.001). No significant trends in adjusted mortality were found for the total study population (AOR, 1.01 [1.00-1.02]; p = 0.150); however, a significant reduction was found for the serious subgroup (AOR, 0.95 [0.92-0.98]; p = 0.002), and a significant increase was found for the critical subgroup (AOR, 1.02 [1.01 1.03]; p = 0.004). CONCLUSION: Total study population trends showed a reduction in rates of craniotomy and increase in craniectomy and ICP rates without any change in outcome. Despite significant adaptations in neurosurgical practice patterns from 2003 to 2013, only patients with serious head injuries are experiencing improved survival. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III; therapeutic study, level IV. PMID- 26885990 TI - Re: Contact isolation is a risk factor for venous thromboembolism in trauma patients. PMID- 26885991 TI - Issues regarding patient assessment scores that focus on acid base changes in fracture patients. PMID- 26885992 TI - Hyperoxic resuscitation following hemorrhage: Good, harmless, or harmful? PMID- 26885993 TI - The state of the union: Nationwide absence of uniform guidelines for the prehospital use of tourniquets to control extremity exsanguination. AB - BACKGROUND: After the Sandy Hook shootings and the resulting Hartford Consensus, as well as the recent Boston Marathon bombing, the need for a uniform, detailed, and aggressive prehospital extremity exsanguination control protocol became clear. We hypothesized that most states within the United States lack a detailed uniform protocol. METHODS: We performed a systematic nationwide assessment of emergency medical services (EMS) prehospital extremity exsanguination control protocols. An online search (updated February 7, 2015) identified state-, region , or county-specific EMS protocols in all 50 states. If unavailable online, protocols were retrieved directly by contacting each state's Department of Public Health (or other appropriate agency). Two investigators independently screened each extremity exsanguination control protocol. Protocols were first grouped into three categories: I, tourniquet not mentioned; II, tourniquet mentioned, without specific guidance; III, tourniquet mentioned, with specific guidance related to type, indications, application technique, and safety concerns. Each protocol was then scored on a five-point scale for comparison. RESULTS: Forty-two states (84%) had statewide and 14 (28%) had at least one county-specific protocol. Seven states (16%) had no statewide protocol but at least one county-specific protocol (range, 1-10). Mississippi had neither statewide nor county-specific protocols. Of statewide protocols, 4 (9.5%) were in Category I, 23 (54.8%) in Category II, and 15 (35.7%) in Category III. The mean score for statewide tourniquets was 2.4/5 (SD, 1.25; range, 0-5). Thirteen (31%) statewide protocols referred to "commercial" or "approved" tourniquets; only three (7%) recommended a particular commercial device. The mean score for the county-specific protocols of states with no statewide protocol was 3.10 (SD, 1.56; range, 0-5) CONCLUSIONS: Throughout the United States, there is considerable variability in EMS protocols addressing the management of extremity exsanguination and an alarming absence of specific guidance for tourniquet use. Most states do not have a uniform, detailed, and aggressive prehospital extremity exsanguination control protocol. LEVEL OF EVIDENCE: Epidemiologic and prognostic study, level III. PMID- 26885994 TI - Re: Hyperoxic resuscitation following hemorrhage: Good, harmless, or harmful? PMID- 26885995 TI - Contemporary outcomes of lower extremity vascular repairs extending below the knee: A multicenter retrospective study. AB - OBJECTIVES: To determine the outcomes of vascular injury interventions extending below the knee. METHODS: Vascular injury repairs extending below the knee from January 2008 to December 2014 were collected from six American College of Surgeons Level I trauma centers. Demographics, management, and outcomes were collected and analyzed. RESULTS: A total of 194 vascular injuries were identified. The mean age was 33.7 years, with 88.1% male, and 71.1% had blunt injury. Admission systolic blood pressure was less than 90 mm Hg in 10.8%; prehospital tourniquets were used in 5.6%. Median mangled extremity severity score (MESS) was 6.0 [interquartile range, 6]. Imaging used included computed tomography angiography (58.2%) and angiography (7.2%); with 66 (34.0%) proceeding directly to OR based on examination alone. Vascular interventions were conducted primarily by vascular (66.0%) and trauma (25.3%) surgeons at a median time from injury of 8 hours (interquartile range, 7 hours). Initial interventions included graft interposition (57.7%) with saphenous vein (111) or synthetic graft (1), primary repair (14.9%), endovascular stent-graft (1.5%), and patch angioplasty (2.1%). Fasciotomy was performed at initial operation in 41.8%, and for delayed compartment syndrome in 2.1%. Vascular reintervention was required in 20 patients (6.7%) for bleeding (seven patients) or thrombosis (13 patients). There was a higher reintervention rates for thrombosis among interposition grafts with distal anastomotic sites at the below-knee popliteal compared to those extending to the tibioperoneal trunk or distal trifurcation vessels, but this was not significant. (4/60, 6.7% vs. 6/49, 12.2%; p = 0.34). Postintervention amputation rates were significantly higher among interposition grafts extending distal to the popliteal (4/60 [6.7%] vs. 15/49 [30.6%]; p = 0.006). CONCLUSIONS: The management of vascular injuries extending below the knee remains a complex issue of extremity trauma care. The need for delayed amputation is significantly more common when revascularization below the distal popliteal artery is required. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic/care management study, level IV. PMID- 26885996 TI - Creation of a decision aid for goal setting after geriatric burns: a study from the prognostic assessment of life and limitations after trauma in the elderly [PALLIATE] consortium. AB - OBJECTIVES: We hypothesized that a decision-support aid to predict index admission mortality and discharge disposition for geriatric burns could be constructed using the well-accepted Baux score (age +total body surface area burned) in a geriatric-specific cohort. METHODS: National Burn Repository version 8.0 (2002-2011) was queried for all subjects aged 65 years or older. Baux scores were calculated and patients grouped into deciles. Three discharge outcomes (death,home, discharge to nonhome setting) were measured per decile. A receiver operating characteristic analysis was used to determine optimal Baux score cutpoints based on the Youden Index. The odds of mortality at various Baux score cutoffs were estimated using logistic regression. RESULTS: The sample was composed of 8,001 subjects. Withdrawal of care was documented in 264 deaths; median time to withdrawal was three days. As Baux score increased, three peaks in disposition were seen. Less than 50% of patients with a Baux score of 80 or greater were discharged home. Patients with a moderate Baux score (80-130) had an increased likelihood of discharge to a nonhome setting. Baux scores of 130 or greater were nearly uniformly fatal (mortality, 94-100%). Baux score of 86.15 or less was predictive of discharge home (area under the curve, 0.698; sensitivity, 75.28%; specificity, 54.64%), and a score greater than 93.3 was predictive of mortality (area under the curve, 0.779; sensitivity, 57.46%; specificity, 87.08%). CONCLUSION: For geriatric patients whose Baux scores exceed 86, return to-home rates drop drastically; mortality increases at a score greater than 93, and mortality is nearly universal at a score >=130 or greater. We are piloting a display of these findings as a decision-making aid when setting goals of care with stakeholders after geriatric burns. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III; therapeutic/care management, level IV. PMID- 26885997 TI - Computed tomography abbreviated assessment of sarcopenia following trauma: The CAAST measurement predicts 6-month mortality in older adult trauma patients. AB - BACKGROUND: Older adult trauma patients are at increased risk of poor outcome, both immediately after injury and beyond hospital discharge. Identifying patients early in the hospital stay who are at increased risk of death after discharge can be challenging. METHODS: Retrospective analysis was performed using our trauma registry linked with the social security death index from 2010 to 2014. Age was categorized as 18 to 64 and 65 years or older. We calculated mortality rates by age category then selected elderly patients with mechanism of injury being a fall for further analysis. Computed Tomography Abbreviated Assessment of Sarcopenia for Trauma (CAAST) was obtained by measuring psoas muscle cross-sectional area adjusted for height and weight. Kaplan-Meier survival analysis was performed, and proportional hazards regression modeling was used to determine independent risk factors for in-hospital and out-of-hospital mortality. RESULTS: A total of 23,622 patients were analyzed (16,748, aged 18-64 years; and 6,874, aged 65 or older). In-hospital mortality was 1.96% for ages 18 to 64 and 7.19% for age 65 or older (p < 0.001); postdischarge 6-month mortality was 1.1% for ages 18 to 64 and 12.86% for age 65 or older (p < 0.001). Predictors of in-hospital and postdischarge mortality for ages 18 to 64 and in-hospital mortality for ages 65 or older group included injury characteristics such as ISS, admission vitals, and head injury. Predictors of postdischarge mortality for age 65or older included skilled nursing before admission, disposition, and mechanism of injury being a fall. A total of 57.5% (n = 256) of older patients who sustained a fall met criteria for sarcopenia. Sarcopenia was the strongest predictor of out-of hospital mortality in this cohort with a hazard ratio of 4.77 (95% confidence interval, 2.71-8.40; p < 0.001). CONCLUSION: Out of hospital does not assure out of danger for the elderly. Sarcopenia is a strong predictor of 6-month postdischarge mortality for older adults. The CAAST measurement is an efficient and inexpensive measure that can allow clinicians to target older trauma patients at risk of poor outcome for early intervention and/or palliative care services. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26885998 TI - Contact isolation is a risk factor for venous thromboembolism in trauma patients. PMID- 26885999 TI - Re: Issues regarding patient assessment scores that focus on acid base changes in fracture patients. PMID- 26886002 TI - Acute traumatic coagulopathy in a critically injured pediatric population: Definition, trend over time, and outcomes. AB - BACKGROUND: While our understanding of acute traumatic coagulopathy (ATC) in adults is advancing, the pediatric literature on ATC is limited. Children have a unique injury profile and physiologic response to trauma; however, the impact of this phenomenon on ATC has not been fully elucidated. METHODS: We performed a retrospective review of our trauma registry from 2005 to 2014. Level 1 trauma patients age 0 year to 17 years requiring admission to the intensive care unit were included. Variables included admission vital signs and laboratory studies, product transfusion, injuries, and mortality. Youden index was used to determine optimum cutoff point for admission international normalized ratio (INR) as a predictor of mortality. Logistic regression modeling was used to determine independent predictors of mortality adjusting for hypotension, hypothermia, acidosis, injury severity, hemorrhage, and head injury. chi tests were performed evaluating for association between mortality and 24-hour INR as well as between transfusion and INR correction. RESULTS: A total of 776 patients were analyzed: 29.2% (n = 227) had an admission INR of 1.3 or greater, and 13.3% (n = 103) had an admission INR of 1.5 or greater. Youden index demonstrated optimum cutoff at INR of 1.3 or greater to distinguish survivors and nonsurvivors. Overall mortality rate was 11.1% (n = 86). Elevated INR was independently associated with mortality (odds ratio, 3.77; p < 0.001) after controlling for other predictors in regression modeling. Death was also associated with elevated INR at 24 hours and worsening INR trend over time. Patients who received plasma were equally likely to normalize their INR compared with those who were not transfused (p = nonsignificant). Findings were consistent across age groups. CONCLUSION: INR likely serves as a marker of systemic dysregulation rather than a treatment target in ATC. Elevated admission INR, elevated INR at 24 hours, and overall trend in INR strongly predict mortality in a diverse pediatric trauma population; however, product transfusion did not influence the INR trend or clinical outcome. Further research is warranted to evaluate potential upstream mediators of ATC and targets for intervention in pediatric trauma patients. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26886001 TI - Pattern of law enforcement-related injuries in the United States. AB - BACKGROUND: The pattern of law enforcement-related injuries of police and civilians in the United States is unknown. METHODS: Data were aggregated from the Federal Bureau of Investigations, the Bureau of Justice Statistics, the Centers for Disease Control (CDC) Web-based Injury Statistics Query and Reporting System, and the Nationwide Inpatient Sample (NIS) from 2003 to 2011. Law enforcement related injuries in the CDC Web-based Injury Statistics Query and Reporting System and the NIS were identified using E-codes 970-976, which are meant to identify "injuries inflicted by the police or other law-enforcing agents, including military on duty, in the course of arresting or attempting to arrest lawbreakers, suppressing disturbances, maintaining order, and other legal action." RESULTS: The CDC reported a total of 715,118 nonfatal injuries and 3,156 fatal injuries from 2003 to 2011. In contrast, for the same period, the NIS identified a total of 3,958 patients, ranging from 348 to 572 per year. Among the injured, 1,548 (48.0%) were white, 866 were black (26.8%), and 605 were Hispanic (18.8%); 1,011 patients (25.5%) were injured by firearms, while 2,304 (58.2%) experienced blows or manhandling. Firearm-injured hospitalized patients are more likely to be male, black or Hispanics, and in the age group of 18 years to 39 years. CONCLUSION: The majority of law enforcement-related injuries are among white or black young men. Hispanic patients are more likely to be injured by a firearm than struck. When injured by firearm, white and black patients are more likely to die compared with Hispanic patients. Unfortunately, data about these injuries are scattered across multiple data systems. A uniform national system to aggregate these data sources is needed to better understand the scope of the problem, for both law enforcement personnel and civilians. LEVEL OF EVIDENCE: Epidemiologic study, level III. PMID- 26886000 TI - Not all prehospital time is equal: Influence of scene time on mortality. AB - BACKGROUND: Trauma is time sensitive, and minimizing prehospital (PH) time is appealing. However, most studies have not linked increasing PH time with worse outcomes because raw PH times are highly variable. It is unclear whether specific PH time patterns affect outcomes. Our objective was to evaluate the association of PH time interval distribution with mortality. METHODS: Patients transported by emergency medical services in the Pennsylvania trauma registry from 2000 to 2013 with a total PH time (TPT) of 20 minutes or longer were included. TPT was divided into three PH time intervals: response, scene, and transport time. The number of minutes in each PH time interval was divided by TPT to determine the relative proportion each interval contributed to TPT. A prolonged interval was defined as any one PH interval contributing equal to or greater than 50% of TPT. Patients were classified by prolonged PH interval or no prolonged PH interval (all intervals < 50% of TPT). Patients were matched for TPT, and conditional logistic regression determined the association of mortality with PH time pattern, controlling for confounders. PH interventions were explored as potential mediators, and PH triage criteria used identify patients with time-sensitive injuries. RESULTS: There were 164,471 patients included. Patients with prolonged scene time had increased odds of mortality (odds ratio, 1.21; 95% confidence interval, 1.02-1.44; p = 0.03). Prolonged response, transport, and no prolonged interval were not associated with mortality. When adjusting for mediators including extrication and PH intubation, prolonged scene time was no longer associated with mortality (odds ratio, 1.06; 95% confidence interval, 0.90-1.25; p = 0.50). Together, these factors mediated 61% of the effect between prolonged scene time and mortality. Mortality remained associated with prolonged scene time in patients with hypotension, penetrating injury, and flail chest. CONCLUSION: Prolonged scene time is associated with increased mortality. PH interventions partially mediate this association. Further study should evaluate whether these interventions drive increased mortality because they prolong scene time or by another mechanism, as reducing scene time may be a target for intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III. PMID- 26886003 TI - The painful truth: The documentation burden of a trauma surgeon. AB - BACKGROUND: Implementation of the electronic medical record (EMR) has introduced several unintended consequences, including increased documentation demands. The purpose of this study was to define the EMR documentation burden and its economic impact at a busy regional Level I trauma center, comparing attending trauma surgeons (TSs) with orthopedic surgeons (OSs), and neurosurgeons (NSs). METHODS: The EMR was queried to determine the number of attending documentation entries during 2014 for TS, OS, and NS. The eight TSs were then surveyed to estimate the time it took to write each note type, and this was used to calculate the total time needed for documentation. The hospital financial database was queried for 2014 hospital charges and work relative value units (WRVUs) for TSs, OSs, and NSs to generate a comparison. The charges and WRVUs were broken down into those generated from nonprocedural documentation and procedures. RESULTS: During 2014, there were 5,864 trauma activations with 3,111 patient admissions. The attending TSs wrote a total of 26,455 documentation entries. Of these notes, 92% were from inpatients, and 74% were progress notes. Documentation time estimates for TSs demonstrated that it took 1,760.5 hours or 73.3 twenty-four-hour days to complete these 26,455 notes. Financial data revealed that 44% of the TS charges were directly related to nonprocedural documentation, compared with 14% for OSs and 7% for NSs. Evaluation of WRVUs demonstrated that 55% of the TS WRVUs were directly related to nonprocedural documentation, compared with 28% for OSs and 19% for NSs. CONCLUSION: The EMR has introduced a significant documentation burden to the busy TSs. This documentation burden is critical for defining hospital charges and WRVUs, and it differs from that of OSs and NSs. Workflow changes, such as the introduction of scribes, may lessen the documentation burden and improve hospital charges and WRVUs of the TSs. PMID- 26886004 TI - Valproic acid-mediated myocardial protection of acute hemorrhagic rat via the BCL 2 pathway. AB - BACKGROUND: Hemorrhage is a major cause of morbidity and mortality among trauma patients. The pathophysiologic changes following acute severe hemorrhage and tissue hypoxia lead to an imbalance of protein acetylation. Histone deacetylase inhibitors (HDACIs) were reported to restore the acetylation imbalance and serve as potential drugs for treating severe hemorrhage. However, the molecular mechanism of HDACI-mediated cytoprotection remains unclear. In this study, we examined the myocardial protective effects and respective mechanism of the HDACI valproic acid (VPA) administered during hemorrhagic and hypoxic stress in vivo and in vitro. METHODS: In vivo, the therapeutic effect of VPA was evaluated in acute severe hemorrhagic rats, and the expressions of BCL-2 signal pathway molecules were observed in rat heart tissues. To explore the molecular mechanism of VPA-mediated myocardial protection, a cobalt chloride (CoCl2)-induced hypoxia model of rat H9c2 cardiomyoblasts was applied to mimic hypoxic injury raised by acute hemorrhage. RESULTS: VPA administration significantly improved the 4-hour survival rate of hemorrhagic animals from 55% to 100% and protected H9c2 cells against CoCl2-induced hypoxic injury at a dose of between 12.5 MUM and 100 MUM. Increased expression of BCL-2 messenger RNA was observed following VPA treatment in the heart tissues of hemorrhagic rats (approximately 4.9-fold) and in H9c2 cells that survived CoCl2-induced hypoxia (approximately 4.9-fold). Western blot analysis showed a concomitant increase in BCL-2 protein expression and Akt phosphorylation following VPA treatment. The cytoprotective activity of VPA was diminished by triciribine-mediated inhibition of Akt activation and by silencing of BCL-2 gene expression. CONCLUSION: These findings suggest that VPA protects myocardial cells from hemorrhagic and hypoxic stress through the Akt/BCL-2 survival pathway, indicating a potential use of HDACIs for acute severe hemorrhage treatment. PMID- 26886005 TI - When children become adults and adults become most hypercoagulable after trauma: An assessment of admission hypercoagulability by rapid thrombelastography and venous thromboembolic risk. AB - BACKGROUND: Thrombelastography (TEG) maximal amplitude (mA) has also been shown to reflect hypercoagulability and increased venous thromboembolism (VTE) risk in adult trauma patients. Based on these previous works, we sought to identify when children become adults with respect to TEG mA values and whether this correlated with VTE risk. METHODS: We evaluated all trauma patients admitted from January 2010 to December 2013 who were highest-level activations. Age was evaluated as a continuous variable, followed by a categorical evaluation. TEG mA values were evaluated as continuous and dichotomous (hypercoagulable, mA >= 65 mm). Logistic regression was then constructed controlling for age categories, sex, and injury severity to assess the association with TEG mA values and VTE risk. RESULTS: A total of 7,194 Level 1 trauma patients were admitted during this time frame (819 were <18 years of age). The likelihood of mA equal to or greater than 65 mm remained at 35% to 37% through age 30 years with significant increases observed at ages 31 years to 35 years (45%) and 46 years to 50 years (49%), both p < 0.01. When controlling for injury severity, race, and sex, logistic regression demonstrated that every 5-year increase in age (after age 30 years) was associated with a 16% increased likelihood of hypercoagulability at admission. Beginning with age 1 year, VTE risk remained at 1.5% or less until age 13 years where it increased to 2.3%, increasing again at age 15 years to 5.1%. Two additional significant increases were identified between ages 31 years and 35 years (5.5%) as well as 46 years and 50 years (7.6%), both p < 0.001. Logistic regression demonstrated a 3.4-fold increased risk for VTE among those aged 31 years to 50 years compared with those who are younger than 30 years. The same model noted a 2.3-fold increased risk compared with those who are older than 50 years. CONCLUSION: Beginning at age 13 years, children transition toward adult hypercoagulability, as evidenced by elevated TEG mA values and VTE risk. However, the greatest VTE risk (and highest likelihood of hypercoagulable mA) is among those adults 31 years to 50 years of age. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III. PMID- 26886006 TI - Object Recognition in Flight: How Do Bees Distinguish between 3D Shapes? AB - Honeybees (Apis mellifera) discriminate multiple object features such as colour, pattern and 2D shape, but it remains unknown whether and how bees recover three dimensional shape. Here we show that bees can recognize objects by their three dimensional form, whereby they employ an active strategy to uncover the depth profiles. We trained individual, free flying honeybees to collect sugar water from small three-dimensional objects made of styrofoam (sphere, cylinder, cuboids) or folded paper (convex, concave, planar) and found that bees can easily discriminate between these stimuli. We also tested possible strategies employed by the bees to uncover the depth profiles. For the card stimuli, we excluded overall shape and pictorial features (shading, texture gradients) as cues for discrimination. Lacking sufficient stereo vision, bees are known to use speed gradients in optic flow to detect edges; could the bees apply this strategy also to recover the fine details of a surface depth profile? Analysing the bees' flight tracks in front of the stimuli revealed specific combinations of flight maneuvers (lateral translations in combination with yaw rotations), which are particularly suitable to extract depth cues from motion parallax. We modelled the generated optic flow and found characteristic patterns of angular displacement corresponding to the depth profiles of our stimuli: optic flow patterns from pure translations successfully recovered depth relations from the magnitude of angular displacements, additional rotation provided robust depth information based on the direction of the displacements; thus, the bees flight maneuvers may reflect an optimized visuo-motor strategy to extract depth structure from motion signals. The robustness and simplicity of this strategy offers an efficient solution for 3D-object-recognition without stereo vision, and could be employed by other flying insects, or mobile robots. PMID- 26886007 TI - Isolating Influenza RNA from Clinical Samples Using Microfluidic Oil-Water Interfaces. AB - The effective and robust separation of biomolecules of interest from patient samples is an essential step in diagnostic applications. We present a platform for the fast extraction of nucleic acids from clinical specimens utilizing paramagnetic PMPs, an oil-water interface, a small permanent magnet and a microfluidic channel to separate and purify captured nucleic acids from lysate in less than one minute, circumventing the need for multiple washing steps and greatly simplifying and expediting the purification procedure. Our device was able to isolate influenza RNA from clinical nasopharyngeal swab samples with high efficiency when compared to the Ambion(r) MagMAXTM Viral RNA Isolation Kit, sufficiently separating nucleic acid analytes from PCR-inhibiting contaminants within the lysate while also critically maintaining high integrity of the viral genome. We find that this design has great potential for rapid, efficient and sensitive nucleic acid separation from patient sample. PMID- 26886008 TI - Estrogen Deficiency Leads to Further Bone Loss in the Mandible of CKD Mice. AB - BACKGROUND: Chronic kidney disease (CKD) has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants. The aim of this study was to investigate the effects of estrogen deficiency on the mandibular bone in CKD mice. METHODS: Forty eleven week-old female C57BL mice were used in this study. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and ovariectomy (OVX), respectively. After 8 weeks, the mice were sacrificed, and their mandibles were collected for micro-CT analysis and histological examination. RESULTS: All the mice survived the experimental period. Serum measurements confirmed a significant increase in BUN in the CKD group that was further increased by OVX. OVX led to significant decreases in both the BV/TV and cortical thickness of the mandibular bone in CKD mice. CONCLUSION: In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice. PMID- 26886009 TI - Predictors of Extubation Success in Patients with Posterior Fossa Strokes. AB - OBJECTIVE: Posterior fossa stroke is unique in its presentation and outcomes, and mechanical ventilation is commonly used in the management of these patients. We aimed to identify predictors of extubation success in patients with posterior fossa stroke, who require mechanical ventilation. DESIGN: We included consecutive adult patients admitted to the neurosciences ICU from January 2003 to December 2012. Extubation failure was defined as re-intubation within 7 days of extubation. A modified Rankin Scale score of 0-3 was considered a good outcome. MEASUREMENTS AND MAIN RESULTS: We identified 150 patients with mean age of 65 +/- 15.7 years with posterior fossa strokes; 77 (51 %) were hemorrhagic, and 73 (49 %) were ischemic. The most common reason for intubation was depressed consciousness (54 %). Fifty-two (35 %) were successfully extubated, 18 (12 %) failed extubation, 17 (11 %) patients had tracheostomy without attempted extubation, and 63 (42 %) were transitioned to palliative care prior to extubation. In the logistic regression analysis, controlling for transition to palliative care, Glasgow Coma Score (GCS) score >6 at the time of intubation (p = 0.020), mechanical ventilation for less than 7 days (p = 0.004), and surgical evacuation of a hematoma (p = 0.058) were independently associated with successful extubation. The presence of cough, gag reflex, and absence of pneumonia/atelectasis were not associated with successful extubation. Success of extubation predicted a good outcome at hospital discharge. CONCLUSIONS: In posterior fossa stroke patients with a GCS <= 6 at the time of intubation and who remain intubated for more than 1 week, extubation is less likely to be successful, and tracheostomy should be considered. PMID- 26886010 TI - Controlled Hypercapnia Enhances Cerebral Blood Flow and Brain Tissue Oxygenation After Aneurysmal Subarachnoid Hemorrhage: Results of a Phase 1 Study. AB - BACKGROUND: This study investigated if cerebral blood flow (CBF) regulation by changes of the arterial partial pressure of carbon dioxide (PaCO2) can be used therapeutically to increase CBF and improve neurological outcome after subarachnoid hemorrhage (SAH). METHODS: In 12 mechanically ventilated poor-grade SAH-patients, a daily trial intervention was performed between day 4 and 14. During this intervention, PaCO2 was decreased to 30 mmHg and then gradually increased to 40, 50, and 60 mmHg in 15-min intervals by modifications of the respiratory minute volume. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary endpoints. Intracranial pressure was controlled by an external ventricular drainage. RESULTS: CBF reproducibly decreased during hyperventilation and increased to a maximum of 141 +/- 53 % of baseline during hypercapnia (PaCO2 60 mmHg) on all days between day 4 and 14 after SAH. Similarly, StiO2 increased during hypercapnia. CBF remained elevated within the first hour after resetting ventilation to baseline parameters and no rebound effect was observed within this time-span. PaCO2-reactivities of CBF and StiO2 were highest between 30 and 50 mmHg and slightly decreased at higher levels. CONCLUSION: CBF and StiO2 reproducibly increased by controlled hypercapnia of up to 60 mmHg even during the period of the maximum expected vasospasm. The absence of a rebound effect within the first hour after hypercapnia indicates that an improvement of the protocol is possible. The intervention may yield a therapeutic potential to prevent ischemic deficits after aneurysmal SAH. PMID- 26886011 TI - First-line therapy for treatment-naive patients with advanced/metastatic renal cell carcinoma: a systematic review of published randomized controlled trials. AB - In the recent years, a number of targeted therapies have been approved for first line treatment of patients with metastatic renal cell carcinoma. A systematic review was conducted to assess the clinical efficacy, safety and effect of all first-line treatments evaluated to date on health-related quality of life (HRQoL). A systematic search of Embase, Cochrane and MEDLINE databases was performed to identify randomized controlled trials (1980-2015) evaluating any targeted therapy/immunotherapy against placebo or any other targeted intervention/immunotherapy in treatment-naive patients with metastatic renal cell carcinoma. Conference proceedings from major cancer congresses (2007-2015) were handsearched. Sixteen randomized controlled trials were identified, mostly phase III. Overall, targeted therapies were associated with either improved [sunitinib, bevacizumab+interferon alpha (IFNalpha) and temsirolimus] or comparable (sorafenib) progression-free survival (PFS) versus IFNalpha monotherapy. Sunitinib demonstrated comparable PFS and overall survival to pazopanib, comparable PFS to sorafenib and shorter PFS compared with bevacizumab+IFNalpha (although no conclusions were made with regard to superiority/inferiority). Compared with sorafenib, tivozanib demonstrated a significantly longer PFS, and both tivozanib and axitinib demonstrated higher response rates. Nintedanib demonstrated comparable PFS and overall survival to sunitinib in a phase II trial. Temsirolimus, sunitinib and sorafenib treatment led to better HRQoL versus IFNalpha; pazopanib was associated with better HRQoL versus sunitinib. No direct meta-analyses or indirect treatment comparison analysis were undertaken because of noncomparability of the trials. In general, targeted therapies demonstrated favourable clinical efficacy and improved HRQoL compared with IFNalpha monotherapy. The newer therapies, tivozanib and axitinib (but not nintedanib), appeared to exhibit greater clinical benefit (response rate) than older tyrosine kinase inhibitors. PMID- 26886012 TI - Proposed technique for open repair of a small umbilical hernia and rectus divarication with self-gripping mesh. AB - INTRODUCTION: There are a group of patients in which umbilical or epigastric hernias co-exist with rectus divarication. These patients have weak abdominal musculature and are likely to pose a higher risk of recurrence following umbilical hernia repair. We would like to describe a technique for open repair of small (<4 cm) midline hernias in patients with co-existing rectus divarication using self-adhesive synthetic mesh. The use of a self-adhesive mesh avoids the need for suture fixation of the mesh in the superior portion of the abdomen, allowing for a smaller skin incision. RESULTS: In 173 patients, preperitoneal self-fixating mesh has been used for the repair of midline hernias <4 cm in diameter. In 58 of these patients, the mesh was extended superiorly to reinforce a concurrent divarication. DISCUSSION: The described technique offers a simple option for open repair of small midline hernias in patients with co-existing rectus divarication, to decrease the risk of upper midline recurrence in an at risk patient group. This initial case series is able to demonstrate a suitably low rate of recurrence and complications. PMID- 26886013 TI - The use of Vicryl mesh in a porcine model to assess its safety as an adjunct to posterior fascial closure during retromuscular mesh placement. AB - BACKGROUND: Posterior component separation has become a common approach to complex abdominal wall reconstructions. This technique includes creation of an extraperitoneal retromuscular space for subsequent large synthetic mesh reinforcement. In certain cases, when complete restoration of "posterior" layer is precluded by significant tissue loss/damage, one proposed strategy is to replace the posterior fascia with an absorbable synthetic polyglactin (Vicryl) mesh. However, the safety of this strategy to prevent mesh-related visceral complication is unknown. Herein, we aimed to characterize mesh-viscera adhesion profiles and host tissue response of synthetic mesh either exposed directly to the viscera, or protected with Vicryl mesh. METHODS: Using adult Yorkshire pigs, 5 * 5 cm pieces of mesh were secured to the intact peritoneum in each of the four quadrants (n = 6 pigs, 24 mesh samples). The study groups were Vicryl (V), Marlex (M), Softmesh (S), Marlex + Vicryl construct (MV), Softmesh + Vicryl construct (SV). The self-made composite meshes were then implanted with the Vicryl side facing the exposed viscera. The pigs were survived for 60 days. At necropsy, grossly, the extent and tenacity of visceral adhesions were evaluated using established scales. Histologically, all specimens for fibrous encapsulation on the visceral surface of the mesh were reviewed by an experienced pathologist blind to meshes used. RESULTS: At necropsy, all Vicryl meshes were completely resorbed. The mean adhesion and tenacity scores for M and MV were 1.8 and 1.1 (P > 0.05), 2.0 and 1.5 (P > 0.05), respectively; while the mean adhesion extent scores and tenacity scores for S and SV were 2.0 and 1.2 (P > 0.05), 2.0 and 1.7 (P > 0.05). No significant difference in adhesion extent and tenacity was observed between Synthetic and Vicryl composite mesh groups. Histologically, Marlex + Vicryl mesh and Softmesh + Vicryl mesh constructs had thicker fibrous capsules than the corresponding unprotected Marlex and Soft mesh implants. Furthermore, visceral adhesions in the composite groups were noted to be to the fibrous capsule and not synthetic mesh itself. CONCLUSION: Utilization of the absorbable polyglactin (Vicryl) mesh as a separating layer between a synthetic mesh and intestines, did not reduce adhesions across various mesh types and composites. Histologically, however, a thick fibrous capsule replaced the Vicryl mesh and may be an important layer to prevent intestinal erosion into retromuscular synthetic meshes. PMID- 26886014 TI - Robust Classification of Small-Molecule Mechanism of Action Using a Minimalist High-Content Microscopy Screen and Multidimensional Phenotypic Trajectory Analysis. AB - Phenotypic screening through high-content automated microscopy is a powerful tool for evaluating the mechanism of action of candidate therapeutics. Despite more than a decade of development, however, high content assays have yielded mixed results, identifying robust phenotypes in only a small subset of compound classes. This has led to a combinatorial explosion of assay techniques, analyzing cellular phenotypes across dozens of assays with hundreds of measurements. Here, using a minimalist three-stain assay and only 23 basic cellular measurements, we developed an analytical approach that leverages informative dimensions extracted by linear discriminant analysis to evaluate similarity between the phenotypic trajectories of different compounds in response to a range of doses. This method enabled us to visualize biologically-interpretable phenotypic tracks populated by compounds of similar mechanism of action, cluster compounds according to phenotypic similarity, and classify novel compounds by comparing them to phenotypically active exemplars. Hierarchical clustering applied to 154 compounds from over a dozen different mechanistic classes demonstrated tight agreement with published compound mechanism classification. Using 11 phenotypically active mechanism classes, classification was performed on all 154 compounds: 78% were correctly identified as belonging to one of the 11 exemplar classes or to a different unspecified class, with accuracy increasing to 89% when less phenotypically active compounds were excluded. Importantly, several apparent clustering and classification failures, including rigosertib and 5-fluoro-2' deoxycytidine, instead revealed more complex mechanisms or off-target effects verified by more recent publications. These results show that a simple, easily replicated, minimalist high-content assay can reveal subtle variations in the cellular phenotype induced by compounds and can correctly predict mechanism of action, as long as the appropriate analytical tools are used. PMID- 26886015 TI - Finding the needle in a haystack: identification of cases of Lynch syndrome with MLH1 epimutation. AB - Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome. MLH1 epimutations are characterized by the soma wide distribution of methylation of a single allele of the MLH1 promoter accompanied by constitutive allelic loss of transcription. 'Primary' MLH1 epimutations, considered pure epigenetic defects, tend to arise de novo in patients without a family history or any apparent genetic mutation. These demonstrate non-Mendelian inheritance. 'Secondary' MLH1 epimutations have a genetic basis and have been linked to non-coding genetic alterations in the vicinity of MLH1. These demonstrate autosomal dominant inheritance. Despite convincing evidence of their role in causing Lynch-type cancers, routine screening for MLH1 epimutations has not been widely adopted. Complicating factors may include: the need to perform additional methylation-based testing beyond the standard genetic screening for a germline mutation; the lack of a consensus algorithm for the selection of patients warranting MLH1 epimutation testing; overlapping molecular pathology features of MLH1 methylation and loss of MLH1 expression with more prevalent sporadic MSI cancers; the rarity of MLH1 epimutation; the variable inter-generational inheritance patterns; and the cost effectiveness of screening. Nevertheless, a positive molecular diagnosis of MLH1 epimutation is clinically important because carriers have a high personal risk of developing metachronous Lynch-type cancers, and their relatives may also be at risk of carriage. Extending existing universal and clinic-based screening algorithms for Lynch syndrome to include an additional arm of selection criteria for cases warranting MLH1 epimutation testing could provide a cost-effective means of diagnosing these cases. PMID- 26886016 TI - A phase 1b study of erlotinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated advanced pancreatic cancer: an Academic Oncology GI Cancer Consortium study. AB - PURPOSE: Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit. This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy. METHODS: In this open-label, phase 1b study, patients with previously untreated, advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1, 8, and 15, and once daily oral erlotinib. A standard "3 + 3" design was used. Dose level 1 (DL1) for gemcitabine (mg/m(2))/nab-paclitaxel (mg/m(2))/erlotinib (mg) was 1000/125/100, respectively, with de-escalation to DL-1 (1000/100/100), DL-2b (1000/75/100), and DL-3 (1000/75/75). The maximum tolerated dose (MTD) was defined by occurrence of dose-limiting toxicity (DLT) in <=1 of six patients within the first cycle. Efficacy was assessed with CT scans performed at two cycle intervals. RESULTS: Nineteen patients were enrolled. DLTs occurred in two patients at DL1, three patients at DL-1, two patients at DL-2b, and one patient at DL-3. The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL-3 (1000/75/75). In analyses of efficacy among 14 evaluable patients, partial responses were observed in four of six patients at DL1, one of two patients at DL 2b, and two of six patients at DL-3. CONCLUSION: The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at standard single-agent dosing of all drugs. However, significant clinical activity was noted, even at DL-3. Further study of the combination will need to incorporate reduced dosing. PMID- 26886017 TI - Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy. AB - PURPOSE: Risk of infection increases with severity and duration of chemotherapy induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day. METHODS: We combined individual patient data from four Amgen-sponsored clinical trials in which patients with cancer were randomized to receive pegfilgrastim either the same day as chemotherapy or the next day. Severity and duration of ANC suppression were calculated using area over the curve (AOC, the area over the ANC-time response curve and below a given clinical threshold). AOC of ANC and incidences of CIN and FN were compared by day of pegfilgrastim use. RESULTS: The analysis included 95 same-day patients and 97 next-day patients. Despite similar ANC at baseline, ANC at nadir was higher among next-day patients than same-day patients. Mean AOC of ANC (cutoff 0.5 * 10(9)/L) among next-day patients was lower by 0.30 (95 % confidence interval: 0.16, 0.43) 10(9)/L * day than same-day patients in cycle 1. Next-day patients had lower incidences of CIN than same-day patients, but there were no significant differences in incidences of FN. CONCLUSIONS: Patients who received pegfilgrastim the day after chemotherapy had less severe and shorter suppression of ANC than patients who received pegfilgrastim the same day as chemotherapy. PMID- 26886018 TI - Platinum-based drugs: past, present and future. AB - Platinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of human neoplasms. Their clinical success is, however, limited due to severe side effects and intrinsic or acquired resistance to the treatment. Much effort has been put into the development of new platinum anticancer complexes, but none of them has reached worldwide clinical application so far. Nedaplatin, lobaplatin and heptaplatin received only regional approval. Some new platinum complexes and platinum drug formulations are undergoing clinical trials. Here, we review the main classes of new platinum drug candidates, such as sterically hindered complexes, monofunctional platinum drugs, complexes with biologically active ligands, trans-configured and polynuclear platinum complexes, platinum(IV) prodrugs and platinum-based drug delivery systems. For each class of compounds, a detailed overview of the mechanism of action is given, the cytotoxicity is compared to that of the clinically used platinum drugs, and the clinical perspectives are discussed. A critical analysis of lessons to be learned is presented. Finally, a general outlook regarding future directions in the field of new platinum drugs is given. PMID- 26886019 TI - A retrospective review of the type of anaesthesia used for LLETZ: proposal for a categorisation audit tool. AB - BACKGROUND: Large loop excision of the transformation zone (LLETZ) is the most common form of treatment for cervical pre-cancer. The majority of procedures should be performed under local anaesthesia (LA) in an outpatient setting. AIM: To review the reasons behind choice of general anaesthesia (GA) for LLETZ and to devise a categorisation tool for audit purposes. METHODS: Review of the type of anaesthesia and histopathological findings for all cases of LLETZ performed at Wexford General Hospital between January 2010 and June 2013 inclusive. RESULTS: Of the 970 cases reviewed, 829 (85.5 %) were performed under LA and 141 (14.5 %) under GA. In five of the 141 GA cases the indication could not be established. The remaining 136 cases could be classified into three categories based on their indications for choosing GA: Category I: 46 cases (33.8 %) where there was associated pathology requiring treatment under GA. Category II: 56 cases (41.2 %) where the colposcopist anticipated difficulty with the procedure and decided on GA. Category III: 34 remaining cases (25 %), where GA was requested by the patient. During the study period the GA rate decreased significantly from 19.4 to 10 % due to a decrease in category II numbers. Higher rates of complete excision of pre-cancer were not found in the GA group. CONCLUSIONS: The use of GA for LLETZ rarely confers benefits in terms of diagnostic or therapeutic quality indicators. The categorisation we propose is a simple audit tool that could be adopted by all colposcopy units to reduce the rate of GA. PMID- 26886021 TI - Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs). AB - In recent years, remarkable advances in the ability to diagnose genetic disorders have been made. The identification of disease-causing genes allows the development of gene-specific therapies with the ultimate goal to develop personalized medicines for each patient according to their own specific genetic defect. In-depth genotyping of many different genes has revealed that ~12% of inherited genetic disorders are caused by in-frame nonsense mutations. Nonsense (non-coding) mutations are caused by point mutations, which generate premature termination codons (PTCs) that cause premature translational termination of the mRNA, and subsequently inhibit normal full-length protein expression. Recently, a gene-based therapeutic approach for genetic diseases caused by nonsense mutations has emerged, namely the so-called translational read-through (TR) therapy. Read through therapy is based on the discovery that small molecules, known as TR inducing drugs (TRIDs), allow the translation machinery to suppress a nonsense codon, elongate the nascent peptide chain, and consequently result in the synthesis of full-length protein. Several TRIDs are currently under investigation and research has been performed on several genetic disorders caused by nonsense mutations over the years. These findings have raised hope for the usage of TR therapy as a gene-based pharmacogenetic therapy for nonsense mutations in various genes responsible for a variety of genetic diseases. PMID- 26886020 TI - Advances in the management of severe aortic stenosis. AB - BACKGROUND: Recent developments in the management of severe aortic stenosis have resulted in a paradigm shift in the way we view the condition. Patients previously denied intervention in the form of surgical aortic valve replacement (SAVR) are now candidates for transcatheter aortic valve implantation and the risk and age profiles of those undergoing SAVR are rising with the ageing population. This review article is designed to provide an overview of developments in the surgical management of severe aortic stenosis. We also discuss the expanding role of minimally invasive surgical approaches to outline the current techniques available to treat patients with severe aortic stenosis. METHODS: PubMed was searched using the terms 'severe aortic stenosis', 'surgical aortic valve replacement', 'transcatheter aortic valve replacement', 'mechanical aortic valve replacement' and 'sutureless aortic valve replacement'. Selection of articles was based on peer review, journal and relevance. Where possible articles from high-impact factor peer review journals were included. RESULTS: Minimally invasive operative approaches include mini-sternotomy and mini-thoracotomy. Sutureless aortic prostheses reduce aortic cross-clamp time and cardiopulmonary bypass time; however, long-term follow-up data are unavailable at this time. Mechanical prostheses are advised for those under 60. CONCLUSION: Multiple advances in the surgical management of aortic stenosis have occured in the past decade. An evolving spectrum of surgical and transcatheter interventions is now available depending on patient age and operative risk. PMID- 26886023 TI - Pharmacological or Genetic Activation of Hsp70 Protects against Loss of Parkin Function. AB - Mutations of parkin are a prevalent genetic contributor to familial Parkinson's disease (PD). As a key regulator of protein and mitochondrial homeostasis, parkin plays a pivotal role in maintaining dopaminergic neuronal survival. However, whereas Drosophila parkin null mutants exhibit prominent parkinsonian features, parkin-deficient mice generally lack an overt phenotype. Here, we found that the expression of Hsp70 along with several other members of the chaperone family is elevated in parkin null mice, suggesting a possible compensatory mechanism for the loss of parkin function in these mice that could have masked their phenotype. Supporting this, we demonstrate that the enhancement of chaperone function induced either pharmacologically via 17-AAG treatment or genetically via Hsp70 overexpression can protect cells against proteolytic and mitochondrial stress in a manner that is similar to that brought about by parkin overexpression. Importantly, we further showed that enhanced chaperone activity can ameliorate the pathological phenotypes in Drosophila parkin null mutants, which suggests the ability of chaperones to phenocopy parkin function. Taken together, our results suggest that Hsp members may act as compensatory factors for parkin loss of function and that the exploitation of these factors may be of potential therapeutic value. PMID- 26886025 TI - Importance of immunisation of elderly subjects before immunosuppressive treatment. PMID- 26886026 TI - Parents' reactions to testing for herpes simplex virus type 2 as a biomarker of sexual activity in Botswana junior secondary school students. AB - Background Use of sexual activity biomarkers in HIV prevention trials has been widely supported to validate self-reported data. When such trials involve minors, researchers may face challenges in obtaining parental buy-in, especially if return of results procedures uphold the confidentiality and privacy rights of minors and preclude parental access to test results. In preparation for a randomised controlled trial (RCT) with junior secondary school (JSS) students in Botswana, a formative assessment was conducted to assess parents' opinions and concerns about testing for herpes simplex virus type 2 (HSV-2) (biomarker of sexual activity) as part of the RCT. METHODS: Six focus groups were held with parents (n=32) of JSS students from urban, peri-urban and rural communities. Parents were asked their opinions of students being tested for HSV-2 and procedures for blood sample collection and return of results. RESULTS: Overall, parents were supportive of HSV-2 testing, which they thought was a beneficial sexual health resource for adolescents and parents, and a motivation for parent child communication about HSV-2, sexual activity and sexual abuse. Some parents supported the proposed plan to disclose HSV-2 test results to adolescents only, citing the importance of adolescent privacy and the possibility of HSV-2 positive adolescents being stigmatised by family members. Conversely, opposing parents requested parental access to results. These parents were concerned that adolescents may experience distress following a positive result and withhold this information thereby reducing parents' abilities to provide support. Parents were also concerned about support for victims of sexual abuse. CONCLUSION: Although the present study demonstrates that parents can be accepting of sexual activity biomarker testing of adolescents, more research is needed to identify best approaches for returning test results. PMID- 26886028 TI - [Finde needle aspiration of peripheral lymph nodes--A method with more potential]. PMID- 26886029 TI - [Erythema nodosum: Many possible causes]. PMID- 26886030 TI - [Erythema nodosum: Many possible causes--in reply]. PMID- 26886027 TI - Having Two Ears Facilitates the Perceptual Separation of Concurrent Talkers for Bilateral and Single-Sided Deaf Cochlear Implantees. AB - OBJECTIVES: Listening to speech with multiple competing talkers requires the perceptual separation of the target voice from the interfering background. Normal hearing listeners are able to take advantage of perceived differences in the spatial locations of competing sound sources to facilitate this process. Previous research suggests that bilateral (BI) cochlear-implant (CI) listeners cannot do so, and it is unknown whether single-sided deaf (SSD) CI users (one acoustic and one CI ear) have this ability. This study investigated whether providing a second ear via cochlear implantation can facilitate the perceptual separation of targets and interferers in a listening situation involving multiple competing talkers. DESIGN: BI-CI and SSD-CI listeners were required to identify speech from a target talker mixed with one or two interfering talkers. In the baseline monaural condition, the target speech and the interferers were presented to one of the CIs (for the BI-CI listeners) or to the acoustic ear (for the SSD-CI listeners). In the bilateral condition, the target was still presented to the first ear but the interferers were presented to both the target ear and the listener's second ear (always a CI), thereby testing whether CI listeners could use information about the interferer obtained from a second ear to facilitate perceptual separation of the target and interferer. RESULTS: Presenting a copy of the interfering signals to the second ear improved performance, up to 4 to 5 dB (12 to 18 percentage points), but the amount of improvement depended on the type of interferer. For BI CI listeners, the improvement occurred mainly in conditions involving one interfering talker, regardless of gender. For SSD-CI listeners, the improvement occurred in conditions involving one or two interfering talkers of the same gender as the target. This interaction is consistent with the idea that the SSD CI listeners had access to pitch cues in their normal-hearing ear to separate the opposite-gender target and interferers, while the BI-CI listeners did not. CONCLUSIONS: These results suggest that a second auditory input via a CI can facilitate the perceptual separation of competing talkers in situations where monaural cues are insufficient to do so, thus partially restoring a key advantage of having two ears that was previously thought to be inaccessible to CI users. PMID- 26886033 TI - [58-year old woman with primary biliary cirrhosis and crepitations]. PMID- 26886035 TI - [57-year-old patient with unclear cutaneous finding]. PMID- 26886036 TI - [Question about weight loss is a must]. PMID- 26886024 TI - Balancing self-renewal against genome preservation in stem cells: How do they manage to have the cake and eat it too? AB - Stem cells are endowed with the awesome power of self-renewal and multi-lineage differentiation that allows them to be major contributors to tissue homeostasis. Owing to their longevity and self-renewal capacity, they are also faced with a higher risk of genomic damage compared to differentiated cells. Damage on the genome, if not prevented or repaired properly, will threaten the survival of stem cells and culminate in organ failure, premature aging, or cancer formation. It is therefore of paramount importance that stem cells remain genomically stable throughout life. Given their unique biological and functional requirement, stem cells are thought to manage genotoxic stress somewhat differently from non-stem cells. The focus of this article is to review the current knowledge on how stem cells escape the barrage of oxidative and replicative DNA damage to stay in self renewal. A clear statement on this subject should help us better understand tissue regeneration, aging, and cancer. PMID- 26886037 TI - [Weight loss in cancer patients]. AB - Cancer patients are regularly affected by malnutrition which often leads to a worsened quality of life and activity in daily living, more side effects and complications during anticancer treatment and shorter survival times. The early diagnosis and treatment of malnutrition are therefore relevant components of oncological treatment. The assessment of the nutritional status and determination of the body-mass-index should be done in every patient with cancer. The clinical examination delivers important findings and indications for malnutrition. Bioimpedance analysis can deliver additional objective information. The treatment of malnutrition should start early and follows a step-wise escalation reaching from nutritional counseling to enteral nutritional support to parenteral nutrition. PMID- 26886038 TI - [Gastrointestinal causes of weight loss: clinical presentation, diagnostic workup and therapy]. AB - This review describes the gasterointestinal entities, their pathophysiology, clinical presentation, diagnostic workup and therapy that typically involve weight loss as the major presenting symptom. The differentiation of malassimilation into maldigestion and malabsorption is clinically mostly not helpful. Instead primary malasssimilation can be distinguished from secondary due to another disease. Celiac disease, lambliasis, small bowel CD, CVIDS and Whipple's disease result in loss of absorptive surface. Chronic intestinal pseudobstruction leads to weight loss through dysmotility and postprandial pain. Microscopic colitis involves some weight loss and needs to be considered because of its high prevalence. Exocrine pancreatic insufficiency and the various protein loosing enteropathies may be primary or secondary syndromes. Dumping, bile acid malabsorption and short bowel syndrome occur after typical operative procedures. Chronic radiation enteritis, chronic intestinal ischemia and intestinal diabetic polyneuropathy are due to chronic intestinal injury. PMID- 26886040 TI - [Hydrogen Breath Tests]. AB - In the field of gastroenterology hydrogen breath test are used for the diagnosis of carbohydrate malabsorption and small intestine bacterial overgrowth. This paper provides information on performing a hydrogen breath test and shows potential sources of error. PMID- 26886039 TI - [Anorexia nervosa as differential diagnosis in underweight patients]. AB - Anorexia nervosa is a differential diagnosis in underweight patients, especially in young underweight women. Diagnostic criteria for anorexia nervosa are self induced weight loss due to restrictive eating or purging behaviour, intense fear of gaining weight and disturbance in the way in which one's shape is experienced, undue influence of body weight on self-evaluation and persistent lack of recognition of the seriousness of the current low body weight. Anorexia nervosa is associated with numerous medical complications. PMID- 26886041 TI - [66-year old female patient with vitreous and mucosal bleeding]. AB - HISTORY AND CLINICAL FINDINGS: We report on a 66-year-old female patient, who presented with a new occurrence of mucosal bleeding and also developed a vitreous hemorrhage. INVESTIGATIONS AND DIAGNOSIS: The bleeding symptoms were caused by an acquired von Willebrand disease (VWD) associated with Waldenstrom macroglobulinemia. In this context, acquired VWD disease results from a dysfunction of the von Willebrand factor (VWF) caused by monoclonal immunoglobulin of type IgM. TREATMENT AND COURSE: Chemotherapy led to normalization of VWF levels and activity, and a complete remission of the bleeding symptoms. CONCLUSIONS: Acquired VWD should be considered in patients with acquired bleeding tendency. Vitreous hemorrhage as observed in our patient is an unusual bleeding symptom induced by hemorrhagic disorders and has to our knowledge not yet been reported in association with this entity. PMID- 26886042 TI - [Cardiopulmonary Comorbidities]. AB - Cardiac and pulmonary diseases are primary causes of global morbidity and mortality. Since the prevalence of both cardiac and pulmonary diseases increases with age, cardiopulmonary comorbidities inflict especially the elderly. Due to the tight physiological connection of the heart and the lung, diseases of both organs affect each other beyond a mere coincidence. At the same time, due to the similarity of their respective symptoms, their differentiation is challenging in clinical practice and therefore, comorbidities can be easily overlooked. This article provides an overview on the characteristics of cardiopulmonary comorbidities and their specific-, but also mutual pathophysiology. PMID- 26886043 TI - [Type 2 diabetes--criteria for the selection of the antidiabetic drug]. AB - Modern treatment of type 2 diabetes follows a patient-centered approach. Blood glucose targets depend on patients' individual situation e. g. age, disease duration and comorbidities. Today physicians can choose from several antidiabetics with different modes of action. Based on national guidelines on the step-wise treatment of type 2 diabetes these substances come into consideration after lifestyle intervention and initial pharmacotherapy with metformin proved to be insufficient. Results from clinical trials have in part shown significant differences between distinct drug classes regarding efficacy, risk of hypoglycemia and effect on body weight. Cardiovascular safety is another important aspect to consider. This balance between efficacy and safety is reflected more and more by analyzing a combined endpoint "reaching individual HbA1c-target without hypoglycemia and weight gain". A guideline- and evidence based classification of present therapeutic options aims to support orientation in diabetes practice. PMID- 26886044 TI - [When to terminate resuscitation in adults?]. AB - Resuscitation in cardiac arrest rarely results in survival with a good neurologic outcome. It is therefore a common problem to decide when resuscitation should not be initiated or an ongoing attempt has to be terminated. Resuscitation attempts should be withheld or terminated if there is a do not resuscitate order (DNR), if resuscitation is not in accordance with the presumptive will of the patient or does not have a chance to allow the patient to continue an independent living. As long as ventricular fibrillation or pulseless ventricular tachycardia are present, however, resuscitation should be continued. Also in pulmonary embolism prolonged resuscitation measures may be necessary. In out-of-hospital cardiac arrest resuscitation may be stopped when the three criteria are met: not witnessed arrest, no ventricular fibrillation or pulseless tachycardia, and no return of spontaneous circulation before arrival at the hospital. According to current guidelines in-hospital resuscitation can be terminated if the patient is in asystole for at least 20 minutes. In any case termination of a resuscitation attempt is an individual decision where all possible information on circumstances and on the patient should be taken into account. PMID- 26886045 TI - [Assisted suicide in Germany: medical diagnoses and personal reasons of 117 decedents]. AB - BACKGROUND: In Germany both scientific and public debates on physician assisted suicide often focus on patients with unbearable suffering in terminal condition. Proponents of physician assisted suicide bring forward the argument that there are end-of-life situations where only assisted suicide can bring relief from intolerable pain, dyspnea or other symptoms. But does focusing on unbearable symptoms in terminal condition reflect the reality of assisted suicide? Our data from 117 assisted suicides in Germany indicates that the reasons for assisted suicide are more complex than the current debate in Germany suggests. METHODS: We analyzed diagnoses and reasons that prompted patients to suicide with the help of the German right-to-die organization "Sterbehilfe Deutschland" (StHD) between 2010 and 2013. 118 case reports of assisted suicide published by StHD were evaluated retrospectively. RESULTS: Between 2010 and 2013 StHD provided assistance in 118 suicides. 71 % of the deceased were women. 67 % were aged 70 years or older. 25,6 % suffered from metastasized cancer, 20,5 % had a severe neurological disease. 23 % suffered from age-associated diseases or disability. 14,5 % of the decedents had a predominant psychiatric diagnose, 7,7 % were physically and mentally healthy. The main reasons for suicide were loss of life perspective in the face of a severe disease (29 %), fear of care dependency (23,9 %), weariness of life without any severe disease (20,5 %). Only 12,8 % named non treatable symptoms as a reason. CONCLUSION: Loss of life perspective in the face of a severe disease, fear of long-term care and weariness of life without any severe disease rather than unbearable suffering of non-treatable symptoms seem to be the most common reasons for members of StHD to commit suicide. These empirical findings should be mentioned in future debates on assisted suicide in Germany. PMID- 26886046 TI - Cannabis Use and Risk of Psychiatric Disorders: Prospective Evidence From a US National Longitudinal Study. AB - IMPORTANCE: With rising rates of marijuana use in the general population and an increasing number of states legalizing recreational marijuana use and authorizing medical marijuana programs, there are renewed clinical and policy concerns regarding the mental health effects of cannabis use. OBJECTIVE: To examine prospective associations between cannabis use and risk of mental health and substance use disorders in the general adult population. DESIGN, SETTING, AND PARTICIPANTS: A nationally representative sample of US adults aged 18 years or older was interviewed 3 years apart in the National Epidemiologic Survey on Alcohol and Related Conditions (wave 1, 2001-2002; wave 2, 2004-2005). The primary analyses were limited to 34 653 respondents who were interviewed in both waves. Data analysis was conducted from March 15 to November 30, 2015. MAIN OUTCOMES AND MEASURES: We used multiple regression and propensity score matching to estimate the strength of independent associations between cannabis use at wave 1 and incident and prevalent psychiatric disorders at wave 2. Psychiatric disorders were measured with a structured interview (Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV). In both analyses, the same set of wave 1 confounders was used, including sociodemographic characteristics, family history of substance use disorder, disturbed family environment, childhood parental loss, low self-esteem, social deviance, education, recent trauma, past and present psychiatric disorders, and respondent's history of divorce. RESULTS: In the multiple regression analysis of 34 653 respondents (14 564 male [47.9% weighted]; mean [SD] age, 45.1 [17.3] years), cannabis use in wave 1 (2001-2002), which was reported by 1279 respondents, was significantly associated with substance use disorders in wave 2 (2004-2005) (any substance use disorder: odds ratio [OR], 6.2; 95% CI, 4.1-9.4; any alcohol use disorder: OR, 2.7; 95% CI, 1.9 3.8; any cannabis use disorder: OR, 9.5; 95% CI, 6.4-14.1; any other drug use disorder: OR, 2.6; 95% CI, 1.6-4.4; and nicotine dependence: OR, 1.7; 95% CI, 1.2 2.4), but not any mood disorder (OR, 1.1; 95% CI, 0.8-1.4) or anxiety disorder (OR, 0.9; 95% CI, 0.7-1.1). The same general pattern of results was observed in the multiple regression analyses of wave 2 prevalent psychiatric disorders and in the propensity score-matched analysis of incident and prevalent psychiatric disorders. CONCLUSIONS AND RELEVANCE: Within the general population, cannabis use is associated with an increased risk for several substance use disorders. Physicians and policy makers should take these associations of cannabis use under careful consideration. PMID- 26886048 TI - Investigation of in vitro cytotoxic, mutagenic and anti-mutagenic effects of shirazolide extracted from Jurinea leptoloba. AB - Shirazolide is an elemanolide isolated from Jurinea leptoloba DC. The aim of this study was to determine the cytotoxic, mutagenic and anti-mutagenic properties of shirazolide from J. leptoloba DC in vitro. Cytotoxicity was measured using a modified MTT (3-(4,5-di methyl thiazol-2-yl)-2,5-di phenyltetrazolium bromide) assay on normal human lymphocytes and tumor HeLa cells, showing that the cytotoxicity of shirazolide is much higher for HeLa cells than for normal lymphocytes. Mutagenic and anti-mutagenic activities of shirazolide were evaluated using the Salmonella typhimurium tester strains TA98 and TA100 showing anti-mutagenic properties against the former strain under metabolic activation. PMID- 26886047 TI - The effect of new dynamic splint in pinch strength in De Quervain syndrome: a comparative study. AB - Objective For patients with De Quervain syndrome using thumb spica orthosis is restricting, so many patient are dissatisfied with using static model. The aim of this study is to compare the effect of modified dynamic and conventional static orthoses on pinch power and functional abilities of hand in De Quervain syndrome. Method In this quasi-experimental study, palmar and lateral pinch strength of the thumb, pain and functional abilities of hand, patient's satisfaction of orthoses, were evaluated after using modified dynamic and conventional static orthosis in two groups. Results Both orthoses improved palmar and lateral pinch strength of the thumb, pain level and functional abilities. In comparison of mentioned variables, there was no significant difference between two groups regarding to pain recovery and abilities improvement (p > 0.05). However, the satisfaction level of the patients who had used dynamic orthosis was higher (p < 0.05). Conclusion It seems, adding a joint to the static thumb spica leads to patient's relief and consequently to their satisfaction. Implications for Rehabilitation The dynamic thumb spica, is easier to use and patients satisfaction is higher than static thumb spica. Therefore, it can be used for conservative treatment of De Quervain syndrome. PMID- 26886049 TI - Late sodium current dysregulation as a causal factor in arrhythmia. PMID- 26886050 TI - Effects of Solvent Dielectric Constant and Viscosity on Two Rotational Relaxation Paths of Excited 9-(Dicyanovinyl) Julolidine. AB - The understanding of the interplay between microenvironment and molecular rotors is helpful for designing and developing of molecular sensors of local physical properties. We present a study on the two rotational relaxation paths of excited 9-(dicyanovinyl) julolidine in several solvents. One rotational path (C-C single bond rotation, taub) quickly leads to the formation of a twisted state. The other path (C?C double-bond rotation, tauc) shows that the populations go back to the ground state directly via a conical intersection between the S1 and ground state. The increase in the solvent dielectric constant shows little effect on the taub lifetime for its small energy barrier (<0.01 eV), but tauc lifetime is increased in larger dielectric constant solvents due to the larger energy gap at conical intersection. Both taub and tauc are increased greatly with the increased solvent viscosity. taub is more sensitive to viscosity than tauc may be due to its larger rotational moiety. PMID- 26886051 TI - Is gerontology ready for anti-racist pedagogy? A survey of educators' practices and perspectives. AB - The older population in the United States is becoming more diverse, bringing increasing attention to the ways in which diversity and multiculturalism are addressed in gerontological education. Although diversity and multiculturalism have long been recognized as important components of the aging experience, our approach to understanding their significance and impact continues to grow and change. Anti-racist pedagogy represents one catalyst to stimulate such change. To evaluate the potential for anti-racist pedagogy in gerontology, this study explored gerontological educators' (N = 121) current practices and perspectives regarding the inclusion of diversity content in their courses, as well as the extent to which they are familiar with and/or use anti-racist pedagogy in their classes. The findings suggest that greater attention to issues of race, ethnicity, and multicultural diversity throughout the gerontological curriculum is needed and wanted. Although respondents were generally unfamiliar with the name anti-racist pedagogy, many indicated that their current teaching practices employed select components of it. Overall, the findings point toward the need for continued exploration of how anti-racist pedagogy may be brought into the gerontological classroom, as well as its implications for future research, policy, and practice. PMID- 26886052 TI - Origin of J-V Hysteresis in Perovskite Solar Cells. AB - High-performance perovskite solar cells (PSCs) based on organometal halide perovskite have emerged in the past five years as excellent devices for harvesting solar energy. Some remaining challenges should be resolved to continue the momentum in their development. The photocurrent density-voltage (J-V) responses of the PSCs demonstrate anomalous dependence on the voltage scan direction/rate/range, voltage conditioning history, and device configuration. The hysteretic J-V behavior presents a challenge for determining the accurate power conversion efficiency of the PSCs. Here, we review the recent progress on the investigation of the origin(s) of J-V hysteresis behavior in PSCs. We discuss the impact of slow transient capacitive current, trapping and detrapping process, ion migrations, and ferroelectric polarization on the hysteresis behavior. The remaining issues and future research required toward the understanding of J-V hysteresis in PSCs will also be discussed. PMID- 26886053 TI - Our Nobel Laureate, Dr. William C. Campbell. PMID- 26886054 TI - ERRATUM . . . PMID- 26886055 TI - Comparison of Replica Exchange Simulations of a Kinetically Trapped Protein Conformational State and its Native Form. AB - Recently an X-ray crystallographic structure of a single-domain antibody was reported with the protein chain trapped in a rare homodimeric form. One of the conformers appears to exhibit a misfolded region, and thus presumably the configurational stability is less favorable. To investigate whether simulation methods can detect any difference between the conformers and buttress the notion that one conformation is trapped on a pathway that incurs lower activation energy to unfold, adaptive temperature-based replica exchange simulations were applied to each chain to model conformational transitions. Simulation results found that the observed crystallographic difference between the two chains in the complementarity determining region CDR2 induces a stark distinction in conformational populations on the energy landscape. An appraisal of the energetic difference between the CDR2 conformations at 300 K revealed a localized order disorder free-energy transition of roughly equivalent to two peptide hydrogen bonds in solution. It was also found that interconversion between the conformers is slower than the rate to unfold and that near an unfolding transition temperature one conformer retained a greater fraction of native-like contacts and energy over a longer time span before fully populating the denatured state, thus verifying the coexistence of a metastable conformation in the crystallographic assembly. PMID- 26886056 TI - Increased visfatin levels are associated with higher disease activity in anti-Jo 1-positive myositis patients. AB - OBJECTIVES: The aim of this study was to evaluate serum levels of visfatin in anti-Jo-1-positive myositis patients, its expression in muscle tissue and to investigate potential relationships between visfatin, B-cell activating factor of the TNF family (BAFF), disease activity and anti-Jo-1 autoantibody levels. METHODS: Serum levels of visfatin and BAFF were measured in 38 anti-Jo-1 positive myositis patients and 35 healthy subjects. Disease activity was evaluated by myositis disease activity assessment tool (MYOACT) using visual analogue scales (VAS) and by serum muscle enzymes. Visfatin expression was evaluated by immunohistochemistry in muscle tissue of myositis patients (n=10) and compared with non-inflammatory control muscle tissue samples from patients with myasthenia gravis (n=5). RESULTS: Serum visfatin and BAFF levels were significantly higher in myositis patients compared to healthy subjects and were associated with clinical muscle activity assessed by VAS. Only serum BAFF levels, but not visfatin levels, positively correlated with muscle enzyme concentrations and anti Jo1 antibody levels. There was a positive correlation between visfatin and BAFF serum levels in myositis patients but a negative correlation was observed in healthy subjects. Visfatin expression was up-regulated in endomysial and perimysial inflammatory infiltrates of muscle tissue from myositis patients. CONCLUSIONS: Up-regulation of visfatin in myositis muscle tissue and an association between increased visfatin levels and muscle disease activity evaluated by MYOACT in anti-Jo-1 positive myositis patients could support possible role of visfatin in the pathogenesis of myositis. PMID- 26886057 TI - Increased oxidative stress in children with attention deficit hyperactivity disorder. AB - OBJECTIVES: The purpose of this study was to investigate oxidative stress in children with attention deficit hyperactivity disorder (ADHD). METHODS: Total oxidant status (TOS), total antioxidant status (TAS), paraxonase-1 (PON-1) and arylesterase (ARE) activity were measured in 76 children (44 boys, 32 girls) diagnosed with ADHD according to the DSM-IV and 78 healthy children (46 boys, 32 girls). RESULTS: Age and sex were similar between the groups (P > 0.05). TOS and the oxidative stress index (OSI) were higher in the patient group than the control group (P < 0.001). PON-1 (P = 0.002), ARE (P = 0.010) activity and TAS (P < 0.001) were lower in the patient group than the control group. DISCUSSION: We found decreased PON-1, ARE activity and TAS, and increased TOS and OSI in children with ADHD. Our study showed that there is significantly increased oxidative stress in children with ADHD. PMID- 26886058 TI - Behavioral Screening and Intervention for Improving Lower-Extremity Arthroplasty Outcomes and Controlling Costs-Reply. PMID- 26886059 TI - Anti-HMGCR antibody-associated necrotizing myopathy: diagnosis and treatment illustrated using a case report. PMID- 26886060 TI - Self-presentation as a function of perceived closeness and trust with romantic partners, friends, and acquaintances. AB - Self-presentation represents behaviors used in establishing an identity with others; such behaviors may differ across various interpersonal relationships. The current article presents two studies examining differences in self-presentation to acquaintances, friends, and romantic partners among college students in relationships. Study 1 was an experiment, and Study 2 utilized a within-subject design. Results showed that individuals engaged in more self-presentation in more established types of relationships. Additionally, both closeness and trust served as moderators, such that those lower in closeness/trust reported more self presentation in more established types of relationships than in less established types of relationships. At higher levels of closeness/trust, the results were somewhat inconsistent, with Study 1 finding no differences between relationship types and Study 2 finding more self-presentation to romantic partners than to friends and acquaintances. These results are among the first to suggest that individuals engage in differing levels of self-presentation, depending on the type of relationship and the extent to which they feel close to and trust the person. PMID- 26886061 TI - Co-occurrence and distribution of deoxynivalenol, nivalenol and zearalenone in wheat from Brazil. AB - Fusarium mycotoxins deoxynivalenol (DON), nivalenol (NIV) and zearalenone (ZEN) were investigated in wheat from the 2009 and 2010 crop years. Samples (n = 745) from commercial fields were collected in four wheat producing regions (WPR) which differed in weather conditions. Analyses were performed using HPLC-DAD. Contamination with ZEN, DON and NIV occurred in 56, 86 and 50%, respectively. Also, mean concentrations were different: DON = 1046 ug kg(-1), NIV < 100 ug kg( 1) and ZEN = 82 ug kg(-1). Co-occurrence of ZEN, DON and NIV was observed in 74% of the samples from 2009 and in 12% from 2010. Wet/cold region WPR I had the highest mycotoxin concentration. Wet/moderately hot region WPR II had the lowest mycotoxin levels. Furthermore, the mean concentration of each mycotoxin was higher in samples from 2009 as compared with those from 2010. Precipitation during flowering or harvest periods may explain these results. PMID- 26886062 TI - Contribution of hot-melt extrusion technology to advance drug delivery in the 21st century. AB - INTRODUCTION: Hot-melt extrusion (HME) technology is applied successfully in the plastic, rubber and food industry. HME has also emerged as an important technology for drug delivery applications in pharmaceutical research and manufacturing because of its process automation and low-cost scale-up properties, which reduce labor costs and capital investment. There are a number of commercial FDA-approved HME-derived products, signifying the commercial feasibility of this novel technique in drug delivery applications. HME is a highly efficient, solvent free continuous processing technique for the development of solid dispersions; thus, research efforts to develop sustained, modified and targeted drug delivery systems to improve the solubility and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) are of interest. AREAS COVERED: This review focuses on both the innovations and applications of HME in the production of pharmaceutical formulations, and on the significant findings of the general principles regarding formulation and process development via HME as described in published articles. EXPERT OPINION: Challenges faced by pharmaceutical companies to produce efficient drug formulations may be partly overcome by HME's advantages - high drug-loading capacity, good content uniformity, cost-effectiveness, and ease of processing scale-up. Nevertheless, HME's high processing temperatures may be an obstacle if adequate knowledge about the product's formulation is lacking. PMID- 26886063 TI - Engineering the Autotroph Methanococcus maripaludis for Geraniol Production. AB - The rapid autotrophic growth of the methanogenic archaeon Methanococcus maripaludis on H2 and CO2 makes it an attractive microbial chassis to inexpensively produce biochemicals. To explore this potential, a synthetic gene encoding geraniol synthase (GES) derived from Ocimum basilicum was cloned into a M. maripaludis expression vector under selection for puromycin resistance. Recombinant expression of GES in M. maripaludis during autotrophic growth on H2/CO2 or formate yielded geraniol at 2.8 and 4.0 mg g(-1) of dry weight, respectively. The yield of geraniol decreased 2-3-fold when organic carbon sources were added to stimulate heterotrophic growth. In the absence of puromycin, geraniol production during autotrophic growth on formate increased to 4.6 mg g(-1) of dry weight. A conceptual model centered on the autotrophic acetyl coenzyme A biosynthetic pathway identified strategies to divert more autotrophic carbon flux to geraniol production. PMID- 26886064 TI - A Guide to Scientific Crowdfunding. AB - Crowdfunding represents an attractive new option for funding research projects, especially for students and early-career scientists or in the absence of governmental aid in some countries. The number of successful science-related crowdfunding campaigns is growing, which demonstrates the public's willingness to support and participate in scientific projects. Putting together a crowdfunding campaign is not trivial, however, so here is a guide to help you make yours a success. PMID- 26886065 TI - Effect of Different Insulin Response Patterns During Oral Glucose Tolerance Test on Glycemia in Individuals with Normal Glucose Tolerance. AB - BACKGROUND: Research is still going on for detecting the earliest glucose homeostasis derangements in individuals, which is crucial for the prevention of glucose intolerance. This cross-sectional study analyzes different insulin response patterns during the oral glucose tolerance test (OGTT) and their implications on glycemia in normoglycemic individuals. SUBJECTS AND METHODS: The sample frame was the "Offspring of Individuals with Diabetes Study" database. All participants underwent OGTT. Blood samples were collected at 0, 30, 60, and 120 min for measurement of insulin, C-peptide, and proinsulin levels. Normal glucose tolerant individuals were selected for analysis. RESULTS: Four hundred fifty subjects (mean age, 25 years) were included and divided into two groups according to timing of plasma insulin peaking during OGTT: Group 1, peaking at 30 min; and Group 2, peaking at 60 or 120 min. Body mass index (BMI) and insulin resistance were comparable between the groups; however, Group 2 showed a significantly higher 60- and 120-min glucose level and lower disposition index. Based on the magnitude of the insulin levels, Group 1 was subdivided into Group N (normal pattern) and Group E (exaggerated pattern) with a 30-min insulin cutoff of 74 MUU/mL (Group E, >=74 MUU/mL). Group 2 was subdivided into Group DL (delayed and limited pattern; 60-min insulin <73.0 MUU/mL and 120-min insulin <80.0 MUU/mL) and Group DE (delayed and exaggerated pattern; 60-min insulin >=73.0 MUU/mL or 120-min insulin >=80.0 MUU/mL). Group DE showed a significantly higher area under the curve (AUC) of glucose compared with the other groups and had a lower disposition index and high-density lipoprotein levels. Group DL had significantly lower insulin resistance and BMI compared with Group E but showed a similar AUC of glucose. CONCLUSIONS: A delayed insulin pattern was associated with higher postprandial glucose levels. Individuals with delayed and exaggerated insulin secretion may have a higher risk for glucose intolerance. PMID- 26886066 TI - Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults. AB - Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naive CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation. PMID- 26886067 TI - Purification and Characterization of Protamine, the Allergen from the Milt of Large Yellow Croaker (Pseudosciaena crocea), and Its Components. AB - The protamine in fish milt can cause anaphylaxis in humans. To determine the allergen in the milt of large yellow croaker (Pseudosciaena crocea), crude extracts were incubated with sera from allergic patients. The results showed that a 12 kDa multicomponent protein was the major allergen in the milt of large yellow croaker. The multicomponent protein was purified, and physicochemical characterization showed that it was a glycoprotein, highly stable in acid-alkali conditions, and weakly retained immunoglobulin E (IgE)-binding activity at high temperatures. Separation and immunoreactivity analysis of the components of the multicomponent protein showed that it had six components, and component 5 had the strongest IgE-binding activity with patient sera. N-terminal sequencing confirmed the multicomponent protein was protamine. Following analysis of protamine from different fish by reversed-phase liquid chromatography and circular dichroism spectra, the protamines from different fish were found to have a similar secondary structure, although their components were different. PMID- 26886068 TI - Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease. AB - The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses. PMID- 26886070 TI - Operative Neurosurgery: The Surgeon's Armamentarium. PMID- 26886069 TI - Quaternary Structure of Fur Proteins, a New Subfamily of Tetrameric Proteins. AB - The ferric uptake regulator (Fur) belongs to the family of the DNA-binding metal responsive transcriptional regulators. Fur is a global regulator found in all proteobacteria. It controls the transcription of a wide variety of genes involved in iron metabolism but also in oxidative stress or virulence factor synthesis. When bound to ferrous iron, Fur can bind to specific DNA sequences, called Fur boxes. This binding triggers the repression or the activation of gene expression, depending on the regulated genes. As a general view, Fur proteins are considered to be dimeric proteins both in solution and when bound to DNA. In this study, we have purified Fur from four pathogenic strains (Pseudomonas aeruginosa, Francisella tularensis, Yersinia pestis, and Legionella pneumophila) and compared them to Fur from Escherichia coli (EcFur), the best characterized of this family. By using a series of "in solution" techniques, including multiangle laser light scattering and small-angle X-ray scattering, as well as cross-linking experiments, we have shown that the Fur proteins can be classified into two groups, according to their quaternary structure. The group of dimers is represented by EcFur and YpFur and the group of very stable tetramers by PaFur, FtFur, and LpFur. Using PaFur as a case study, we also showed that the dissociation of the tetramers into dimers is necessary for binding of Fur to DNA, and that this dissociation requires the combined effect of metal ion binding and DNA proximity. PMID- 26886073 TI - Optimisation of microstructured biodegradable finasteride formulation for depot parenteral application. AB - This study aimed to use the biocompatibility features of the biodegradable polymers to prepare depot injectable finasteride (FIN) microspheres for the treatment of benign prostatic hyperplasia. FIN microspheres were prepared utilising an emulsion-solvent evaporation/extraction technique. The Box-Behnken experimental design was adopted to optimise the preparation process. FIN plasma levels in albino rabbits were determined after injection with optimised FIN microspheres formula and compared with oral FIN suspension. Results revealed that the optimum microspheres displayed an amended sustained release pattern with lower initial burst. The cumulative FIN % released after 25 days was in the range 27.83-73.18% for F4 and F1, respectively. The optimised formula, with 50.0% (X1), and 22.316% (X2) and 1.38% (X3) showed 6.503 MUm, 93.213%, 14.574%, and 64.838% for Y1, Y2, Y3, and Y4, respectively. In vivo studies displayed a sustained release pattern with minimal initial burst release when injected into rabbits. PMID- 26886074 TI - Experiences of Antihomosexual Attitudes and Young Black Men Who Have Sex with Men in the South: A Need for Community-Based Interventions. AB - PURPOSE: In 2012, Jackson, Mississippi, had the third highest incidence rate of human immunodeficiency virus (HIV) among young Black men who have sex with men (MSM). The goal of this qualitative study (the initial phase of an HIV prevention clinical trial) was to explore how cultural norms regarding antihomosexual attitudes interfere with the safe sex practices and relationship norms of young Black MSM in Mississippi. METHODS: Nine focus groups (N = 54) were conducted with young Black MSM aged 18-29. Participants were recruited through medical providers at local sexually transmitted infection clinics and through community organizers at local LGBT outreach programs. The data were analyzed through the use of grounded theory, multiple coders for consistency and intercoder reliability, and a qualitative data analysis software. RESULTS: Three major themes were identified during the analysis: (1) resiliency and condom use, (2) inconsistent condom use among closeted young Black MSM, and (3) intimate partner violence (IPV) among closeted young Black MSM. Black MSM in Mississippi continue to be highly stigmatized within their social networks (i.e., families, sexual partners, and community). CONCLUSIONS: The findings suggest that cultural and community norms regarding antihomosexual attitudes may be a barrier to the practices of safe sex and a contributing factor to IPV among young Black MSM. There is a need for tailored interventions that address these cultural norms and establish social and community support for young Black MSM in Mississippi. PMID- 26886075 TI - The association between combination antiretroviral adherence and AIDS-defining conditions at HIV diagnosis. AB - Combination antiretroviral therapy (cART) has changed the clinical course of HIV. AIDS-defining conditions (ADC) are suggestive of severe or advanced disease and are a leading cause of HIV-related hospitalizations and death among people living with HIV/AIDS (PLWHA) in the USA. Optimal adherence to cART can mitigate the impact of ADC and disease severity on the health and survivability of PLWHA. The objective of this study was to evaluate the association between ADC at HIV diagnosis and optimal adherence among PLWHA. Using data from the 2008 and 2009 Medicaid data from 29 states, we identified individuals, between 18 and 49 years, recently infected with HIV and with a cART prescription. Frequencies and descriptive statistics were conducted to characterize sample. Univariate and multivariable Poisson regression analyses were employed to evaluate the association optimal cART adherence (defined as >= 95% study days covered by cART) and ADC at HIV diagnosis (>=1 ADC) were assessed. Approximately 17% of respondents with ADC at HIV diagnosis reported optimal cART adherence. After adjusting for covariates, respondents with an ADC at HIV diagnosis were less likely to report optimal cART adherence (adjusted prevalence ratio (APR) = 0.64, 95% confidence intervals (CI), 0.54-0.75). Among the covariates, males (APR=1.10, 95% CI, 1.02-1.19) compared to females were significantly more likely to report optimal adherence while younger respondents, 18-29 years (APR=0.67, 95% CI, 0.57 0.77), 30-39 years (APR=0.86, 95% CI, 0.79-0.95) compared to older respondents were significantly less likely to report optimal adherence. PLWHA with ADC at HIV diagnosis are at risk of suboptimal cART adherence. Multiple adherence strategies that include healthcare providers, case managers, and peer navigators should be utilized to improve cART adherence and optimize health outcomes among PLWHA with ADC at HIV diagnosis. Targeted adherence programs and services are required to address suboptimal adherence in this population. PMID- 26886076 TI - Differentiating Between Cancer and Inflammation: A Metabolic-Based Method for Functional Computed Tomography Imaging. AB - One of the main limitations of the highly used cancer imaging technique, PET-CT, is its inability to distinguish between cancerous lesions and post treatment inflammatory conditions. The reason for this lack of specificity is that [(18)F]FDG-PET is based on increased glucose metabolic activity, which characterizes both cancerous tissues and inflammatory cells. To overcome this limitation, we developed a nanoparticle-based approach, utilizing glucose functionalized gold nanoparticles (GF-GNPs) as a metabolically targeted CT contrast agent. Our approach demonstrates specific tumor targeting and has successfully distinguished between cancer and inflammatory processes in a combined tumor-inflammation mouse model, due to dissimilarities in angiogenesis occurring under different pathologic conditions. This study provides a set of capabilities in cancer detection, staging and follow-up, and can be applicable to a wide range of cancers that exhibit high metabolic activity. PMID- 26886078 TI - Consequences of Electron-Density Manipulations on the X-ray Photoelectron Spectroscopic Properties of Ferrocenyl-beta-diketonato Complexes of Manganese(III). Structure of [Mn(FcCOCHCOCH3)3]. AB - Reaction of [Mn3(OAc)6O.3H2O](+) (1) with ferrocenyl beta-diketones of the type FcCOCH2COR with R = CF3 (2a) and CH3 (2b), Ph = C6H5 (2c), and Fc = Fe(II)(eta(5) C5H4)(eta(5)-C5H5) (2d) yielded a series of ferrocene-functionalized beta diketonato manganese(III) complexes 3a-3d, respectively, of general formula [Mn(FcCOCHCOR)3]. The mixed-ligand beta-diketonato complex [Mn(FcCOCHCOFc)2(FcCOCHCOCH3)] (4) was obtained by reacting mixtures of diketones 2b and 2d with 1. A single-crystal X-ray structure determination of 3b (Z = 2, triclinic, space group P1) highlighted a weak axial elongating Jahn-Teller effect and a high degree of bond conjugation. An X-ray photoelectron spectroscopic study, by virtue of linear relationships between group electronegativities of ligand R groups, chiR, or ?chiR, and binding energies of both the Fe 2p3/2 and Mn 2p3/2 photoelectron lines, confirmed communication between molecular fragments of 2a-2d as well as 3a-3d. This unprecedented observation allows prediction of binding energies from known beta-diketonato side group chiR values. PMID- 26886079 TI - Designing CuOx Nanoparticle-Decorated CeO2 Nanocubes for Catalytic Soot Oxidation: Role of the Nanointerface in the Catalytic Performance of Heterostructured Nanomaterials. AB - This work investigates the structure-activity properties of CuOx-decorated CeO2 nanocubes with a meticulous scrutiny on the role of the CuOx/CeO2 nanointerface in the catalytic oxidation of diesel soot, a critical environmental problem all over the world. For this, a systematic characterization of the materials has been undertaken using transmission electron microscopy (TEM), transmission electron microscopy-energy-dispersive X-ray spectroscopy (TEM-EDS), high-angle annular dark-field-scanning transmission electron microscopy (HAADF-STEM), scanning transmission electron microscopy-electron energy loss spectroscopy (STEM-EELS), X ray diffraction (XRD), Raman, N2 adsorption-desorption, and X-ray photoelectron spectroscopy (XPS) techniques. The TEM images show the formation of nanosized CeO2 cubes (~25 nm) and CuOx nanoparticles (~8.5 nm). The TEM-EDS elemental mapping images reveal the uniform decoration of CuOx nanoparticles on CeO2 nanocubes. The XPS and Raman studies show that the decoration of CuOx on CeO2 nanocubes leads to improved structural defects, such as higher concentrations of Ce(3+) ions and abundant oxygen vacancies. It was found that CuOx-decorated CeO2 nanocubes efficiently catalyze soot oxidation at a much lower temperature (T50 = 646 K, temperature at which 50% soot conversion is achieved) compared to that of pristine CeO2 nanocubes (T50 = 725 K) under tight contact conditions. Similarly, a huge 91 K difference in the T50 values of CuOx/CeO2 (T50 = 744 K) and pristine CeO2 (T50 = 835 K) was found in the loose-contact soot oxidation studies. The superior catalytic performance of CuOx-decorated CeO2 nanocubes is mainly attributed to the improved redox efficiency of CeO2 at the nanointerface sites of CuOx-CeO2, as evidenced by Ce M5,4 EELS analysis, supported by XRD, Raman, and XPS studies, a clear proof for the role of nanointerfaces in the performance of heterostructured nanocatalysts. PMID- 26886077 TI - Spectroscopic Studies of the EutT Adenosyltransferase from Salmonella enterica: Mechanism of Four-Coordinate Co(II)Cbl Formation. AB - EutT from Salmonella enterica is a member of a class of enzymes termed ATP:Co(I)rrinoid adenosyltransferases (ACATs), implicated in the biosynthesis of adenosylcobalamin (AdoCbl). In the presence of cosubstrate ATP, ACATs raise the Co(II)/Co(I) reduction potential of their cob(II)alamin [Co(II)Cbl] substrate by >250 mV via the formation of a unique four-coordinate (4c) Co(II)Cbl species, thereby facilitating the formation of a "supernucleophilic" cob(I)alamin intermediate required for the formation of the AdoCbl product. Previous kinetic studies of EutT revealed the importance of a HX11CCX2C(83) motif for catalytic activity and have led to the proposal that residues in this motif serve as the binding site for a divalent transition metal cofactor [e.g., Fe(II) or Zn(II)]. This motif is absent in other ACAT families, suggesting that EutT employs a distinct mechanism for AdoCbl formation. To assess how metal ion binding to the HX11CCX2C(83) motif affects the relative yield of 4c Co(II)Cbl generated in the EutT active site, we have characterized several enzyme variants by using electronic absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopies. Our results indicate that Fe(II) or Zn(II) binding to the HX11CCX2C(83) motif of EutT is required for promoting the formation of 4c Co(II)Cbl. Intriguingly, our spectroscopic data also reveal the presence of an equilibrium between five-coordinate "base-on" and "base-off" Co(II)Cbl species bound to the EutT active site at low ATP concentrations, which shifts in favor of "base-off" Co(II)Cbl in the presence of excess ATP, suggesting that the base-off species serves as a precursor to 4c Co(II)Cbl. PMID- 26886080 TI - Improving Ribosomal RNA Integrity in Surgically Resected Human Brain Tumor Biopsies. AB - BACKGROUND: Biopsies extracted from brain cancer patients often display degraded ribosomal RNA, which makes them unusable in transcriptomic experiments. This has not been properly documented in previous works aimed at refining the molecular classification of brain cancer. OBJECTIVE: To determine RNA integrity in a large cohort of human brain cancer biopsies and to evaluate different factors that may influence RNA integrity in both a murine model of glioblastoma and in additional subsets of patient biopsies. METHODS: Total RNA was isolated from 255 biopsies of various human brain tumors (HBTs) and processed on a Bioanalyzer. Correct RNA integrity was considered for samples showing either the ribosomal 28S/18S peak ratio >= 1.2 or RNA integrity number >= 6. The time-dependent effect of ex vivo ischemia was evaluated in a murine model, whose results were tested in a new collection of 27 human biopsies. Multiple biopsy sampling was considered in a further set comprising 32 biopsies. RESULTS: The 255 human biopsies revealed a substantial percentage of samples displaying degraded RNA (27.5%). The murine model confirmed the known relevance of ex vivo ischemia time in increased RNA degradation. Human biopsies extracted immediately after cauterization showed a trend toward less RNA degradation. Combining snap freezing and multiple sampling of biopsies, the percentage of patients with degraded RNA was reduced by twofold (15.6%). CONCLUSIONS: We provide a first concise study of factors influencing RNA degradation in HBT biopsies. Immediate biopsy removal after cauterization of the tumor area, snap freezing, and multiple sampling improve RNA quality. PMID- 26886081 TI - Direct Preparation of 3-Iodochromenes from 3-Aryl- and 3-Alkyl-2-propyn-1-ols with Diaryliodonium Salts and NIS. AB - On the basis of a study of the O-phenylation of 3-phenyl-2-propyn-1-ol with diphenyliodonium triflate and t-BuONa, a variety of 4-aryl-3-iodo-2H-benzopyrans were prepared in good to moderate yields in one pot from the reaction of 3-aryl-2 propyn-1-ols with diaryliodonium triflates and t-BuONa, followed by the treatment with N-iodosuccinimide and BF3.OEt2, under transition-metal-free and mild conditions. The formed 4-phenyl-3-iodo-2H-benzopyran was converted into 4-phenyl 2H-benzopyran derivatives through C-C bond formations at the 3-position by Pd catalyzed coupling reactions and into coumarin with oxidants. PMID- 26886084 TI - Coinage metal complexes with bridging hybrid phosphine-NHC ligands: synthesis of di- and tetra-nuclear complexes. AB - A series of P-NHC-type hybrid ligands containing both PR2 and N-heterocyclic carbene (NHC) donors on meta-bis-substituted phenylene backbones, L(Cy), L(tBu) and L(Ph) (R = Cy, tBu, Ph, respectively), was accessed through a modular synthesis from a common precursor, and their coordination chemistry with coinage metals was explored and compared. Metallation of L(Ph).n(HBr) (n = 1, 2) with Ag2O gave the pseudo-cubane [Ag4Br4(L(Ph))2], isostructural to [Ag4Br4(L(R))2] (R = Cy, tBu) (T. Simler, P. Braunstein and A. A. Danopoulos, Angew. Chem., Int. Ed., 2015, 54, 13691), whereas metallation of .HBF4 (R = Ph, tBu) led to the dinuclear complexes [Ag2(L(R))2](BF4)2 which, in the solid state, feature heteroleptic Ag centres and a 'head-to-tail' (HT) arrangement of the bridging ligands. In solution, interconversion with the homoleptic 'head-to-head' (HH) isomers is facilitated by ligand fluxionality. 'Head-to-tail' [Cu2Br2(L(R))2] (R = Cy, tBu) dinuclear complexes were obtained from L(R).HBr and [Cu5(Mes)5], Mes = 2,4,6-trimethylphenyl, which also feature bridging ligands and heteroleptic Cu centres. Although the various ligands L(R)l ed to structurally analogous complexes for R = Cy, tBu and Ph, the rates of dynamic processes occurring in solution are dependent on R, with faster rates for R = Ph. Transmetallation of both NHC and P donor groups from [Ag4Br4(L(tBu))2] to AuI by reaction with [AuCl(THT)] (THT = tetrahydrothiophene) led to L(tBu) transfer and to the dinuclear complex [Au2Cl2L(tBu)] with one L(tBu) ligand bridging the two Au centres. Except for the silver pseudo-cubanes, all other complexes do not exhibit metallophilic interactions. PMID- 26886083 TI - Brain Microvasculature Involvement in ANCA Positive Vasculitis. AB - OBJECTIVE: Endothelial dysfunction is associated with arterial stiffness, a factor that is increasingly recognised as an important determinant of cardiovascular risk. High-flow organs such as the brain and kidneys are particularly sensitive to excessive pressure and flow pulsatility. High, local blood flow is associated with low microvascular impedance, which facilitates the penetration of excessive pulsatile energy into the microvascular bed leading to tissue damage. Systemic endothelial dysfunction and arterial stiffness have been demonstrated in peripheral vessels in associated vasculitis (AAV). Although, the brain involvement is not infrequent in AAV, it has not been evaluated previously. Our aim is to evaluate the involvement of the brain microvasculature in AAV. METHODS: Twenty-three patients with inactive AAV were studied. Brain blood flow was assessed by transcranial Doppler (TCD) and single-photon positron emission tomography (SPECT), structural brain involvement by brain MRI and cognitive scores by Montreal Cognitive Assessment (MoCA) test. RESULTS: Lower mean flow velocity (MFV) was associated to altered SPECT perfusion, higher white matter changes (WMC), lower MoCA scores and younger age (p < 0.05). Middle cerebral artery pulsatility index (MCA-PI) was related to hypertension, diabetes, lower scores on MoCA, increased vasculitis damage index (VDI) and perfusion impairment in SPECT (p < 0.05). These data were reproduced for all intracranial arteries. Up to 88.9% of patients had WMC on MRI. A higher lesion load was associated with age, decreased MoCA and fewer MFV with higher PI. The multivariable linear regression analysis showed that the greater the lesion loads, greater the bifrontal atrophy, MCA-PI and lower MoCA scores. Up to 60.9% of patients presented a decreased MoCA score (p = 0.012). It appeared to be related to VDI (p = 0.04), WMC (p = 0.004) and altered SPECT (p = 0.05). CONCLUSIONS: The alterations in brain perfusion SPECT, the presence of white matter lesions on MRI, as well as increased PI and RI with lower MFV of the cerebral vessels in TCD suggest the presence of microangiopathy in asymptomatic AAV that could lead to cognitive impairment. PMID- 26886082 TI - Hepcidin regulation in the anemia of inflammation. AB - PURPOSE OF REVIEW: Anemia is prevalent in patients with infections and other inflammatory conditions. Induction of the iron regulatory hormone hepcidin has been implicated in the pathogenesis of anemia of inflammation. This review outlines recent discoveries in understanding how hepcidin and its receptor ferroportin are regulated, how they contribute to anemia of inflammation, and how this knowledge may help guide new diagnostic and therapeutic strategies for this disease. RECENT FINDINGS: IL-6 is a primary driver for hepcidin induction in many models of anemia of inflammation, but the SMAD1/5/8 pathway also contributes, likely via Activin B and SMAD-STAT3 interactions at the hepcidin promoter. Hepcidin has an important functional role in many, but not all forms of anemia of inflammation, although hepcidin-independent mechanisms also contribute. In certain populations, hepcidin assays may help target therapy with iron or erythropoiesis-stimulating agents to patients who may benefit most. New therapies targeting the hepcidin-ferroportin axis have shown efficacy in preclinical and early clinical studies. SUMMARY: Recent studies confirm an important role for the hepcidin-ferroportin axis in the development of anemia of inflammation, but also highlight the diverse and complex pathogenesis of this disorder depending on the underlying disease. Hepcidin-based diagnostic and therapeutic strategies offer promise to improve anemia treatment, but more work is needed in this area. PMID- 26886086 TI - Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients. AB - OBJECTIVE: To evaluate melatonin secretion in adult hypopituitary patients with Growth Hormone deficiency (AGHD) on and off replacement therapy. SUBJECTS AND METHODS: We studied 48 subjects: 12 (6 males) untreated AGHD (AGHDnt), 20 (10 males) treated AGHD (AGHDt) and 16 healthy subjects (8 males) as control group (CG). We measured urinary 6-sulfatoxymelatonin (6-SM) in total (24 h samples), nocturnal (6-SMn): 1800-0800 and diurnal samples (6-SMd): 0800-1800. RESULTS: Significant differences were observed among the 3 groups of male subjects, in total 6-SM (p < 0.05), nocturnal 6-SM (p < 0.02) and nighttime-daytime delta values (p < 0.003). CG had significantly higher values than the AGHDnt in total 6 SM (p < 0.01), nocturnal 6-SM (p < 0.05) and nighttime-daytime delta values (p < 0.01). AGHDt patients showed significantly higher levels in nighttime-daytime delta values than AGHDnt patients (p < 0.05). In females, no significant differences were found among the 3 groups studied in total, nocturnal, diurnal or nighttime-daytime delta values. In males, significant correlations were found among total 6-SM (r = 0.58; p = 0.029), nocturnal 6-SM (r = 0.70; p = 0.006) and nighttime-daytime delta values (r = 0.71; p = 0.004) vs. serum IGF-1 levels in subjects evaluated. In females, significant correlations were found among total 6 SM (r = 0.57; p = 0.02) vs. serum IGF-1 levels in subjects evaluated. A tendency towards a significant correlation was found in diurnal 6-SM (r = 0.48; p = 0.07). CONCLUSIONS: Our findings show a sexual dimorphism in 6-SM excretion in AGHD patients and provide an interesting approach to a further understanding of some chronobiological disorders involved in GH deficiency. PMID- 26886087 TI - Radio-contrast agent-induced hyperthyroidism: case report and review of the literature. AB - A 66 year-old woman with a history of a euthyroid multinodular goiter underwent a head and neck computed tomography (CT) scan (total iodine load of 35 g) in order to evaluate the extent of retrosternal expansion. Less than 24 h after the iodine based contrast media (ICM) administration, she presented with symptoms and laboratory findings typical of thyrotoxicosis. She was treated successfully with antithyroid medications. This is the shortest time reported in the literature and it is of clinical importance, as it may have an impact to the recommendations given by the attending physician. Given the fact that a large number of ICM examinations are performed in everyday practice, physicians should be aware of this possible thyroid-specific effect. Prophylactic drugs could be considered in high-risk populations, such as administration of perchlorate and a thionamide class drug to elderly patients with suppressed TSH and/or palpable goiter, started the day before and continued for two weeks after ICM administration. PMID- 26886088 TI - Clinical, hormonal and radiological features of partial Sheehan's syndrome: an Indian experience. AB - Objective The objective of this study was to describe clinical presentation, hormonal profile and imaging characteristics of 21 patients with partial Sheehan's syndrome. Subjects and methods This prospective study was carried out over a period of six years (2008-2013). The evaluation of patients included clinical assessment, hormone estimations and contrast enhanced magnetic resonance imaging of pituitary. Results We documented preservation of gonadotroph, corticotroph and lactotroph function in 71.4, 61.9, and 9.5% of patients respectively. Conclusion To conclude some of the pituitary functions can be preserved in Sheehan's syndrome and this has important implications from the treatment and long term morbidity point of view. PMID- 26886089 TI - Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism. AB - OBJECTIVE: Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH. SUBJECTS AND METHODS: Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear. RESULTS: Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one. CONCLUSIONS: The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH. PMID- 26886091 TI - TSH reference values in the first trimester of gestation and correlation between maternal TSH and obstetric and neonatal outcomes: a prospective Brazilian study. AB - OBJECTIVE: To define the normal range of TSH in the first trimester of gestation and to evaluate the correlation between maternal TSH and obstetric and neonatal outcomes. SUBJECTS AND METHODS: Prospective study. Women without known or clinically suspected thyroid disease and without risk factors for thyroid dysfunction, who became pregnant spontaneously and were initially evaluated up to week 12 of gestation, were included. Women with positive anti-thyroperoxidase antibodies, twin pregnancy, hyperemesis gravidarum, and trophoblastic disease were excluded. RESULTS: In the 660 pregnant women, the mean, median, and 2.5th and 97.5th percentiles of TSH were 0.9, 0.96, 0.04 and 2.68 mIU/L, respectively. TSH was undetectable in 2%, < 0.5 mIU/L in 17.4%, > 2 mIU/L in 9.7%, > 2.5 mIU/L in 4.7%, and > 3 mIU/L in 1%. None of the women received levothyroxine or antithyroid drugs during pregnancy. In addition, there was no difference in obstetric or neonatal outcomes when women with TSH <= 0.1, between 0.1 and 2.5, and between 2.5 and 4 mIU/L were compared. CONCLUSION: In the population studied, the TSH value corresponding to the 97.5th percentile was 2.68 mIU/L in the first trimester of gestation. PMID- 26886090 TI - Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus. AB - Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression. PMID- 26886092 TI - Assessment of the left ventricular function in normotensive prediabetics: a tissue Doppler echocardiography study. AB - OBJECTIVE: Several studies have shown that left ventricular (LV) dysfunction is increased in individuals with diabetes. However, there are scarce data about LV function in prediabetics. This study assessed the early changes in LV diastolic and systolic myocardial function in normotensive prediabetics using tissue Doppler echocardiography (TDE). SUBJECTS AND METHODS: We evaluated 94 patients with prediabetes (mean age of 50.8 +/- 6.9 years, 78 female) without known cardiovascular diseases and 70 healthy volunteers with similar demographic characteristics. Systolic and diastolic function of the left ventricle was evaluated with transthoracic echocardiography according to the latest consensus recommendations including TDE. RESULTS: The mean results of septal and lateral parts of the mitral annulus Pulsed wave TDE showed that myocardial systolic wave (Sm), myocardial early diastolic wave (Em) and Em to atrial peak velocity (Am) ratio were significantly lower whereas early diastolic peak flow velocity (E) to Em ratio, myocardial isovolumetric relaxation time (IVRTm), myocardial isovolumetric contraction time (IVCTm) and myocardial performance index (MPI) values were significantly higher in patients with prediabetes (preDM). In addition, mean left atrium (LA) diameter measured with M-mode echocardiography was significantly higher in prediabetics than controls. CONCLUSION: PreDM is associated with subclinical LV systolic and diastolic dysfunction as evaluated by TDE. PMID- 26886093 TI - Mean platelet volume in patients with prolactinoma. AB - OBJECTIVE: Prolactin is a multifunctional pituitary hormone. The effect of prolactin on platelet activation is not well understood. Prolactinomas are the most common type of pituitary adenomas, and they are medically responsive to dopamine agonists. Mean platelet volume (MPV) is a marker of platelet function and activation. The aim of this study was to evaluate MPV values before and 6 months of cabergoline treatment when normoprolactinemia was achieved. SUBJECTS AND METHODS: A total of 101 newly diagnosed prolactinoma patients and 102 healthy control subjects were included in the study. Patients with hematological disorders that affect MPV and those on medications were excluded. Prolactin, platelet count and MPV levels were recorded before and 6 months after the initiation of cabergoline treatment (0.5 to 1 mg, two times a week). RESULTS: There was no significant difference in platelet count and MPV before and after 6 months of treatment with cabergoline in patients with prolactinoma compared with the control group (p > 0.05). CONCLUSION: Our results showed that MPV, a marker of platelet function, was unchanged in patients with prolactinoma. PMID- 26886094 TI - Clustering of risk factors for cardiometabolic diseases in low-income, female adolescents. AB - OBJECTIVE: To assess the prevalence and clustering patterns of cardiometabolic risk factors among low-income, female adolescents. MATERIALS AND METHODS: Cross sectional study involving 196 students of public schools (11-19 years old). The following risk factors were considered in the analysis: excess weight, central obesity, dyslipidemia, high blood pressure, and high fasting glucose. The ratio between observed and expected prevalence and its confidence interval were used to identify clustering of risk factors that exceeded expected prevalence in the population. RESULTS: The most prevalent risk factors were dyslipidemia (70.9%), and central obesity (39.8%), followed by excess weight (29.6%), and high blood pressure (12.8%). A total of 42.9% of adolescents had two or more risk factors, and 24% had three or more. Excess weight, central obesity, and dyslipidemia were common risk factors in the clustering patterns that showed higher-than-expected prevalence. CONCLUSIONS: Clustering of risk factors (>= two factors) among the adolescents showed considerable prevalence, and there was a non-casual coexistence of excess weight, central obesity, and dyslipidemia (mainly low HDL cholesterol). PMID- 26886095 TI - Cerebellar ataxia as presenting feature of hypothyroidism. AB - Symptoms and signs of the hypothyroidism vary in relation to the magnitude and acuteness of the thyroid hormone deficiency. The usual clinical features are constipation, fatigue, cold intolerance and weight gain. Rarely it can present with neurologic problems like reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Hypothyroidism should be suspected in all cases of ataxia, as it is easily treatable. A 40 year-old male presented with the history facial puffiness, hoarseness of voice and gait-ataxia. Investigations revealed frank primary hypothyroidism. Anti-TPO antibody was positive. Thyroxine was started and patient improved completely within eight weeks. Hypothyroidism can present with ataxia as presenting feature. Hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia. PMID- 26886096 TI - The Evaluation of Serum Copeptin Levels and Some Commonly Seen Thrombophilic Mutation Prevalence in Acute Pulmonary Embolism. AB - Acute pulmonary embolism (PE) is a common, emergent condition and may affect a large number of patients. Copeptin has been indicated to be a sensitive biomarker of arginine vasopressin release, and has diagnostic and prognostic value in various clinical conditions. Genetic mutations are considerable components of thrombophilic diseases, and factor II gene G20210A, (FII20210A), factor V Leiden (FVL, G1691A) and methylenetetrahydrofolate reductase gene C677T (MTHFR677T) single nucleotide polymorphisms are the most common mutations of thrombophilic diseases. In this study, serum copeptin levels were determined in patients with PE and healthy controls, and the results were discussed. The prevalence of some commonly seen thrombophilic mutations was also evaluated in patients with PE. The study included 32 patients (18 male, 14 female) with PE and 24 (13 male, 11 female) age- and gender-matched healthy controls. A significant difference in serum copeptin levels was determined between the patient and control groups (8.58 +/- 4.42 and 4.07 +/- 1.02 pmol/L, respectively). Heterozygous mutant genotype for FII20210A and heterozygous mutant genotype for FVL were observed in 3.1 and 9.4% of patients, respectively. Mutant genotype of 49% was determined for MTHFR677T mutations. It was concluded that copeptin may have diagnostic value for PE. PMID- 26886097 TI - Chromoendoscopy with a Standard-Resolution Colonoscope for Evaluation of Rectal Aberrant Crypt Foci. AB - Colorectal cancer (CRC) is the second most common cause of death worldwide. According to the theory by Vogelstein, colorectal carcinogenesis involves a series of successive changes in the normal colonic mucosa, starting with excessive proliferation and focal disorders of intestinal crypts, followed by adenoma and its subsequent malignant transformation. The first identifiable changes in CRC carcinogenesis are aberrant crypt foci (ACF). ACF are invisible during routine colonoscopy yet are well identifiable in chromoendoscopy using methylene blue or indigo carmine. High-resolution colonoscopes are used for assessment of ACF. The aim of the present study was to evaluate the usefulness of standard-resolution colonoscopy for identification of rectal ACF. The following parameters were evaluated: duration of chromoendoscopy of a given rectal segment, type of ACF, sensitivity and specificity of endoscopy combined with histopathological evaluation. The mean duration of colonoscopy and chromoendoscopy was 26.8 min. In the study population, typical ACF were found in 73 patients (p = 0.489), hyperplastic ACF in 49 (p = 0.328), and dysplastic ACF in 16 patients (p = 0.107). Mixed ACF were observed in 11 individuals (p = 0.073). The sensitivity of the method was found to be 0.96 whereas its specificity 0.99. Identification of rectal ACF using standard-resolution colonoscopy combined with rectal mucosa staining with 0.25% methylene blue is characterised by high sensitivity and specificity. PMID- 26886098 TI - p-Curve and p-Hacking in Observational Research. AB - The p-curve, the distribution of statistically significant p-values of published studies, has been used to make inferences on the proportion of true effects and on the presence of p-hacking in the published literature. We analyze the p-curve for observational research in the presence of p-hacking. We show by means of simulations that even with minimal omitted-variable bias (e.g., unaccounted confounding) p-curves based on true effects and p-curves based on null-effects with p-hacking cannot be reliably distinguished. We also demonstrate this problem using as practical example the evaluation of the effect of malaria prevalence on economic growth between 1960 and 1996. These findings call recent studies into question that use the p-curve to infer that most published research findings are based on true effects in the medical literature and in a wide range of disciplines. p-values in observational research may need to be empirically calibrated to be interpretable with respect to the commonly used significance threshold of 0.05. Violations of randomization in experimental studies may also result in situations where the use of p-curves is similarly unreliable. PMID- 26886099 TI - Staying Connected on the Road: A Comparison of Different Types of Smart Phone Use in a Driving Simulator. AB - Previous research on smart phone use while driving has primarily focused on phone calls and texting. Drivers are now increasingly using their phone for other activities during driving, in particular social media, which have different cognitive demands. The present study compared the effects of four different smart phone tasks on car-following performance in a driving simulator. Phone tasks were chosen that vary across two factors: interaction medium (text vs image) and task pacing (self-paced vs experimenter-paced) and were as follows: Text messaging with the experimenter (text/other-paced), reading Facebook posts (text/self paced), exchanging photos with the experimenter via Snapchat (image, experimenter paced), and viewing updates on Instagram (image, experimenter-paced). Drivers also performed a driving only baseline. Brake reaction times (BRTs) were significantly greater in the text-based conditions (Mean = 1.16 s) as compared to both the image-based conditions (Mean = 0.92 s) and the baseline (0.88 s). There was no significant difference between BRTs in the image-based and baseline conditions and there was no significant effect of task-pacing. Similar results were obtained for Time Headway variability. These results are consistent with the picture superiority effect found in memory research and suggest that image-based interfaces could provide safer ways to "stay connected" while driving than text based interfaces. PMID- 26886101 TI - First steps to understand heat tolerance of temperate maize at adult stage: identification of QTL across multiple environments with connected segregating populations. AB - KEY MESSAGE: Dents were more heat tolerant than Flints. QTL for heat tolerance with respect to grain yield at field conditions were identified considering multiple populations and environments. High temperatures have the potential to cause severe damages to maize production. This study aims to elucidate the genetic mechanisms of heat tolerance under field conditions in maize and the genome regions contributing to natural variation. In our study, heat tolerance was assessed on a multi-environment level under non-controlled field conditions for a set of connected intra- and interpool Dent and Flint populations. Our findings indicate that Dent are more heat tolerant during adult stage than Flint genotypes. We identified 11 quantitative trait loci (QTL) including 2 loci for heat tolerance with respect to grain yield. Furthermore, we identified six heat tolerance and 112 heat-responsive candidate genes colocating with the previously mentioned QTL. To investigate their contribution to the response to heat stress and heat tolerance, differential expression and sequence variation of the identified candidate genes should be subjected to further research. PMID- 26886102 TI - Uncrossed Asymmetry in Pattern Visual Evoked Potentials: A Reappraisal. AB - PURPOSE: To demonstrate the utility of an uncrossed asymmetry in full-field pattern reversal visual evoked potentials (FF-PVEPs) will accurately predict a retrochiasmal lesion confirmed by MRI. METHODS: During an 8-year period, 754 patients had FF-PVEPs performed and analyzed without knowledge of their clinical histories and imaging studies. Interhemispheric amplitude ratios were calculated between N75-P100 and P100-N145 and deemed significant if both demonstrated greater than 50% amplitude asymmetry no matter which eye was stimulated (uncrossed symmetry). RESULTS: We identified 11 patients of 754 patients evaluated for 8 years (1.5%) whose FF-PVEP fulfilled our amplitude criteria. Ten of 11 had retrochiasmal lesions confirmed with MRI for a calculated positive predictive value of 91%. CONCLUSIONS: These data provide initial support for the hypothesis that specified amplitude criteria in FF-PVEPs can provide evidence for a retrochiasmal lesion. An abnormal interhemispheric amplitude ratio in FF-PVEPs is underrecognized as a diagnostic criterion for retrochiasmal lesion prediction. PMID- 26886103 TI - Conductive Plastic Electrodes Reduce EEG Artifact During Pediatric ECMO Therapy. AB - PURPOSE: Extracorporeal membrane oxygenation (ECMO) is a life-saving heart and lung bypass procedure that can cause substantial EEG artifact. Continuous EEG monitoring is nonetheless a helpful neuromonitoring tool for patients receiving ECMO therapy because neurologic complications are frequent, but factors such as sedation, neuromuscular blockade, and hemodynamic instability limit clinical and radiographic evaluation. We examined whether using conductive plastic electrodes in place of conventional gold electrodes reduces artifact in clinical EEG studies of pediatric ECMO patients. METHODS: Four masked electroencephalographers assessed artifact and its impact on overall EEG interpretation in samples from 21 consecutive EEGs recorded during ECMO therapy (14 gold and 7 plastic). A spectral power analysis then quantified 50- to 70-Hz artifact in a larger group of 14 gold and 34 plastic electrode studies during ECMO and 4 non-ECMO gold electrode studies. RESULTS: The masked electroencephalographers identified less artifact (P < 0.001) and indicated greater confidence in the accuracy of EEG interpretation (P < 0.001) among studies recorded with plastic electrodes. In quantitative analyses, ECMO was associated with greater 50- to 70-Hz power among studies using gold electrodes (P < 0.001) and gold electrodes exhibited greater 50- to 70-Hz power than plastic electrodes (P < 0.001). Contrasting studies in which most of the electroencephalographers believed that interpretation was (n = 12; 7 gold and 5 plastic) or was not (n = 7; all gold) compromised by artifact, 50- to 70-Hz power was similarly higher among the compromised studies (P < 0.001). CONCLUSION: Plastic electrodes substantially reduce the burden of electrical artifact in EEG studies performed on pediatric ECMO patients and improve confidence in EEG interpretation. PMID- 26886100 TI - Individual Differences in Scotopic Visual Acuity and Contrast Sensitivity: Genetic and Non-Genetic Influences. AB - Despite the large amount of variation found in the night (scotopic) vision capabilities of healthy volunteers, little effort has been made to characterize this variation and factors, genetic and non-genetic, that influence it. In the largest population of healthy observers measured for scotopic visual acuity (VA) and contrast sensitivity (CS) to date, we quantified the effect of a range of variables on visual performance. We found that young volunteers with excellent photopic vision exhibit great variation in their scotopic VA and CS, and this variation is reliable from one testing session to the next. We additionally identified that factors such as Circadian preference, iris color, astigmatism, depression, sex and education have no significant impact on scotopic visual function. We confirmed previous work showing that the amount of time spent on the vision test influences performance and that laser eye surgery results in worse scotopic vision. We also showed a significant effect of intelligence and photopic visual performance on scotopic VA and CS, but all of these variables collectively explain <30% of the variation in scotopic vision. The wide variation seen in young healthy volunteers with excellent photopic vision, the high test-retest agreement, and the vast majority of the variation in scotopic vision remaining unexplained by obvious non-genetic factors suggests a strong genetic component. Our preliminary genome-wide association study (GWAS) of 106 participants ruled out any common genetic variants of very large effect and paves the way for future, larger genetic studies of scotopic vision. PMID- 26886104 TI - Urinary Dysfunction in Progressive Supranuclear Palsy Compared with Other Parkinsonian Disorders. AB - BACKGROUND: Autonomic urinary dysfunction affects patients with progressive supranuclear palsy (PSP); however, the severity and prevalence of urinary dysfunctions in these patients compared with those observed in patients with Parkinson's disease (PD) and multiple system atrophy (MSA) are unknown. OBJECTIVE: We compared urinary dysfunction characteristics in patients with PSP, PD, and MSA. PATIENTS AND METHODS: Forty-seven patients who satisfied the probable or possible criteria of the National Institute for Neurological Diseases and Stroke and Society for PSP were assessed using the urinary symptoms questionnaire and the urodynamic study at Chiba and Toho Universities (n = 26 and 21, respectively). The results were compared with those of patients with PD and MSA (n = 218 and 193, respectively). RESULTS: The mean disease duration of PSP and the mean age were 2.97 +/- 0.26 and 71.4 +/- 0.88 years, respectively. The mini-mental state examination and frontal assessment battery scores were 22.6 +/- 0.70 and 10.7 +/- 0.49, respectively. Urinary storage and voiding symptoms were observed in 57% and 56% of patients with PSP, respectively. Detrusor overactivity in the urodynamic study was detected in 81% of patients with PSP, which was slightly more than that found in patients with PD (69%) and MSA (67%); however, this was not statistically significant. Postvoid residual volume in patients with PSP was significantly more than that in patients with PD (P < 0.01), but was equivalent to that in patients with MSA. CONCLUSIONS: The present study demonstrated that patients with PSP experienced various urinary dysfunctions. Urinary storage dysfunction in patients with PSP was not different from that in patients with PD or MSA, whereas urinary voiding dysfunction in patients with PSP was milder than that in patients with MSA and more severe than that in patients with PD. These features should be taken into account for the differentiation of PSP from PD and MSA. PMID- 26886105 TI - Peering into the Deep: Characterizing the Internet Search Patterns of Patients with Gynecologic Cancers. AB - Cancer patients are increasingly using the Internet to learn about their disease, connect with others undergoing similar treatments and obtain support outside of the clinical encounter. The goal of this project was to explore how patients with gynecological cancers (ovarian, cervical, and endometrial) used the Internet as an information resource and how this influenced their treatment decisions and interactions with their health care specialists. From 2013 to 2014, ovarian, endometrial, and cervical cancer patients attending a comprehensive cancer centre were invited to complete a 24-item paper questionnaire detailing their experiences in searching the Internet. Twenty-eight patients completed survey. The largest portion of participants had an ovarian cancer diagnosis (61 %), followed by endometrial (29 %) and cervical cancer (11 %). Results indicate that the majority (85 %) of patients used the Internet as a resource to learn about their gynecological cancers. Most respondents (89 %) used Google as their search engine, and some used multiple search engines. The most frequently searched topics included treatment information (85 %), management of symptoms/treatment toxicity (59 %), and alternative treatments (37 %). Many patients (74 %) felt that the Internet was a useful tool for understanding their diagnosis; however, 33 % reported that the Internet was somewhat hard to understand. Most (78 %) patients reported that Internet information increased their understanding of their diagnosis, and 56 % felt it did not affect their decision-making. This study highlights how gynecological patients are accessing cancer information online and how physicians may support this within the clinical setting. PMID- 26886106 TI - Sudden death following accidental ingestion of a button battery by a 17-month-old child: a case study. AB - Cases of ingesting button batteries by children are not common clinical situations in forensic medicine. Although it can be a cause of death when associated with digestive perforations, no cases of sudden death have been reported in the literature. We report the case of a 17-month-old girl who presented at home with haematemesis, followed by failed cardiopulmonary resuscitation. The child had been treated on two occasions for nasopharyngitis, 14 and 18 days prior to her death. The post-mortem scan revealed a radio-opaque foreign body in the oesophagus. The autopsy revealed the presence of a round button battery, 20 mm in diameter, blocking the lumen of the oesophagus in its upper third, associated with two parietal oesophageal ruptures opposite each other. There was limited digestive haemorrhage, but above all significant bronchial inhalation of blood. Toxicology analyses showed slightly increased blood levels of the heavy metals of which the battery was composed (lithium, chromium, manganese and molybdenum). The anatomopathological analyses confirmed the recent nature of these ruptures. Ingestions of button batteries localised at the level of the oesophagus are the cases linking to the highest risk of complications, particularly for batteries with a diameter of more than 20 mm and in children under the age of 4. The main difficulty in such clinical situations is identifying when the ingestion occurred, as more often than not, no witnesses are present. We discuss the advantages of anatomopathology and toxicology examinations targeted towards heavy metals in these forensic situations. PMID- 26886107 TI - The cardiothoracic ratio on post-mortem computer tomography. AB - In clinical practice, the cardiothoracic ratio (CTR) was first utilized on plain chest radiography, and subsequently with computed tomography (CT) to diagnose cardiomegaly with a threshold of 0.5. Using CTR in forensic practice could help to detect cardiomegaly on post-mortem CT (PMCT) prior to the autopsy. However, an adaption of the threshold could be necessary because of post-mortem changes. Our retrospective study aimed to measure the CTR on PMCT and test the possible influence of variables. We selected 109 autopsy cases in which the heart weight was within normal limits. A forensic pathologist and a radiologist measured separately the CTR on axial and scout views on PMCT. We tested the statistical concordance between the two readers and between the axial and scout view and identified factors that could be associated with a modification of the CTR. The CTR measurements revealed an overestimation of the measurements made on scout compared to axial view. The inter-reader correlation was very high for both views. Among the different variables statistically tested, heart dilatation and body mass index (BMI) were the only two factors statistically associated with an augmentation of the CTR. The CTR can be useful in the diagnosis of cardiomegaly on PMCT. However, dilatation of the cardiac chambers caused by acute heart failure may be misinterpreted radiographically as cardiomegaly. Inter-observer reliability in our study was very high. CTR may be overestimated when measured on the scout view. Further investigations with larger cohorts, including cases with cardiac hypertrophy, are necessary to better understand the relationship between radiological CTR and the morphology of the heart. PMID- 26886108 TI - Ultrasound and Electromyography Guidance for Injection of the Longus Colli With Botulinum Toxin for the Treatment of Cervical Dystonia. AB - Cervical dystonia, also called spasmodic torticollis, is a painful condition in which neck muscles contract involuntarily, and may cause abnormal head position or movements. The primary (or first line of) treatment of cervical dystonia is chemodenervation with injection of botulinum toxin into the affected muscles. We report a case of a young man with idiopathic cervical dystonia who developed anterocollis (forward flexion of the neck) not responsive to prior scalene and sternocleidomastoid muscle injections. To safely access the deeper cervical musculature, ultrasound (US) was used in conjunction with electromyography, to inject the longus colli muscles bilaterally. The patient responded well and had no complications. The longus colli has been reported to be injected using electromyography, fluoroscopy, computed tomography, and, less frequently, US. We propose that US guidance is an excellent technique for botulinum toxin injection, especially for deep cervical muscles such as the longus colli. PMID- 26886109 TI - Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity. AB - It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients. PMID- 26886111 TI - Erratum to: Treatment costs of attention deficit hyperactivity disorder in Germany. PMID- 26886110 TI - Back to the future: restricted protein intake for conservative management of CKD, triple goals of renoprotection, uremia mitigation, and nutritional health. AB - Lowering dietary protein intake (DPI) to approximately 0.6-0.8 g/kgBW/day may be renoprotective through various mechanisms, and it has been recommended in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) as a means to also control various metabolic consequences of advanced CKD, such as uremic symptoms, hyperparathyroidism, hypertension, hyperkalemia, and hyperphosphatemia. A meta-analysis in this issue of the Journal suggests that low-protein diet is effective and safe when used to retard progression of CKD and alleviate uremic complications. A potential deleterious consequence of lowering DPI in this population is the development or worsening of protein-energy wasting (PEW), which can contribute to poor clinical outcomes such as higher mortality and morbidity. There is currently insufficient high-level evidence to determine the ideal level of DPI in patients with NDD-CKD with high risk of PEW. For the time being we recommend a DPI of 0.6-0.8 g/kgBW/day, and increasing this as needed on an individual basis in patients with PEW. Further examination of this dilemma in randomized controlled clinical trials will be necessary. PMID- 26886112 TI - The "Majority Illusion" in Social Networks. AB - Individual's decisions, from what product to buy to whether to engage in risky behavior, often depend on the choices, behaviors, or states of other people. People, however, rarely have global knowledge of the states of others, but must estimate them from the local observations of their social contacts. Network structure can significantly distort individual's local observations. Under some conditions, a state that is globally rare in a network may be dramatically over represented in the local neighborhoods of many individuals. This effect, which we call the "majority illusion," leads individuals to systematically overestimate the prevalence of that state, which may accelerate the spread of social contagions. We develop a statistical model that quantifies this effect and validate it with measurements in synthetic and real-world networks. We show that the illusion is exacerbated in networks with a heterogeneous degree distribution and disassortative structure. PMID- 26886113 TI - Glaucoma: Today and Tomorrow. PMID- 26886114 TI - Optical Coherence Tomography Imaging for Glaucoma - Today and Tomorrow. AB - Digital imaging technologies for glaucoma diagnostics have evolved rapidly over the recent years. From time-domain optical coherence tomography (OCT) to spectral domain and swept-source OCTs, the application of OCT for analysis of the anterior chamber angle and the optic nerve head (ONH) is expanding. The second-generation anterior segment swept-source OCT is able to image the configuration of the anterior chamber angle in 3 dimensions in less than 1 second and perform 360 degree analysis of the anterior chamber angle width for detection of angle closure. The morphology, density, and dimensions of the crystalline lens in relation to the anterior chamber can now be examined from the anterior corneal surface to the posterior lens surface, facilitating the investigation of the involvement of the crystalline lens in primary angle closure. Spectral-domain and swept-source OCTs have improved the measurement reliability of the lamina cribrosa and the neuroretinal rim configurations. Studying the deformation of the lamina cribrosa and ONH surfaces is relevant to decipher the mechanisms of ONH damage in the development and progression of glaucoma. Software and algorithms for automatic analysis of the anterior chamber angle dimensions and deformation of the ONH and lamina cribrosa surfaces are required to process large volumetric data sets, and they are under active development. It is expected that new imaging technologies will improve the detection and risk assessment of angle-closure and open-angle glaucomas. PMID- 26886115 TI - Personalizing Intraocular Pressure: Target Intraocular Pressure in the Setting of 24-Hour Intraocular Pressure Monitoring. AB - Determining target intraocular pressure (IOP) in glaucoma patients is multifaceted, requiring attention to many different factors such as glaucoma type, severity of disease, age, race, family history, corneal thickness and hysteresis, and initial IOP. Even with all these variables accounted for, there are still patients who have progression of the disease despite achieving target IOP. Intraocular pressure variability has been identified as a potential independent risk factor for glaucoma progression but is currently difficult to quantify in individual patients. New technologies enabling measurement of both diurnal and nocturnal IOP may necessitate modifying our concept of target pressure. PMID- 26886116 TI - Update on the Prevalence, Etiology, Diagnosis, and Monitoring of Normal-Tension Glaucoma. AB - Glaucoma is a leading cause of blindness worldwide. Normal-tension glaucoma (NTG) is a type of open-angle glaucoma with intraocular pressure measurements always 21 mm Hg or less. A controversy surrounding NTG is the question of whether it should be regarded as a disease within the spectrum of primary open-angle glaucoma or as a distinctive disease entity. Nonetheless, NTG does have distinctive features compared with primary open-angle glaucoma: intraocular pressure-independent risk factors for development of NTG, characteristic patterns of structural and functional damage, and a unique disease course. This review provides an overview and update on the current issues surrounding the prevalence, etiology, diagnosis, and monitoring of NTG. PMID- 26886117 TI - Glaucoma Suspect: Diagnosis and Management. AB - Glaucoma suspect is a diagnosis reserved for individuals who do not definitively have glaucoma at the present time but have characteristics suggesting that they are at high risk of developing the disease in the future based on a variety of factors. This review provides a practical approach to individuals classified as glaucoma suspects caused by one or more of the following risk factors or indicators of disease: ocular hypertension, optic nerve features suggestive of glaucoma, visual field abnormalities, and other characteristics placing them at greater risk than the average population. In addition to diagnostic considerations, this overview provides information on therapeutic approaches to the glaucoma suspect. PMID- 26886118 TI - Ocular Blood Flow and Influencing Factors for Glaucoma. AB - Open-angle glaucoma (OAG) is characterized by optic nerve fiber atrophy and deterioration of the visual field, corresponding to damage to the optic nerve head. Intraocular pressure (IOP) is currently the only evidence-based, treatable risk factor for OAG. However, normal-tension glaucoma, the most common type of OAG in Asia, is a type of glaucoma with an unclear pathogenesis. Glaucoma is suspected to be a multifactorial disease with IOP-dependent and IOP-independent risk factors, including decreased ocular blood flow (OBF), oxidative stress, decreased axoplasmic flow, and genetic background. A number of epidemiological studies have generated strong evidence that OBF may be an especially important risk factor for the progression of glaucoma. Recent innovations in laser speckle flowgraphy and optical coherence tomography-based angiography have allowed us to noninvasively monitor changes in the microcirculation of the optic nerve head with high reproducibility. Laser speckle flowgraphy-derived measurement parameters include mean blur rate and pulse wave form parameters, whereas the main optical coherence tomography angiography-derived parameter is the vessel index. Decreases in these parameters are associated with the severity of glaucomatous damage, and changes are detectible even in the earliest, preperimetric stage of glaucoma. In the future, OBF analysis may improve significantly because of continuing progress in the development of the relevant instruments. This review will summarize possible connections between systemic and OBF abnormalities and OAG, describe the scientific rationale for these connections, and discuss their potential implications. Thus, this review will summarize the role of OBF in glaucoma pathogenesis and discuss the wide range of IOP-independent risk factors. PMID- 26886119 TI - Systemic Associations of Exfoliation Syndrome. AB - Exfoliation syndrome (XFS) is an age-related disease characterized by the production, deposition, and progressive accumulation of a white, fibrillar, extracellular material in many ocular tissues, most prominent on the anterior lens surface and pupillary border. Its prevalence increases steadily with age in all populations. It is the most common identifiable cause of open-angle glaucoma worldwide and is a potentially reversible or even curable disease. First described in Finland in 1917 by Lindberg, it has long been associated with open angle glaucoma. However, in recent years, it is being increasingly reported in conjunction with a multiplicity of both ocular and systemic disorders, and the number of these is expected to grow, particularly with investigations based on attempts to associate other diseases with those genes known to be associated with XFS. Despite the focus on XFS as a cause of open-angle glaucoma for nearly a century, in reality it is still only an ocular manifestation of a protean systemic disease. It is a unique disorder with extensive and often serious ocular and systemic manifestations and not, as it has long been termed, a "form" or "type" of glaucoma. This misconception has delayed research into the molecular and cellular processes involved in its development, and the underestimation of its overall importance and its underlying causative mechanisms have largely been long ignored. The purpose of this article is to review the systemic disorders which are becoming increasingly associated with XFS. Reviews of epidemiology, genetics, biomarkers, molecular mechanisms of development, and ocular findings may be found elsewhere. PMID- 26886120 TI - Update on the Medical Treatment of Primary Open-Angle Glaucoma. AB - Glaucoma comprises a group of progressive, neurodegenerative disorders characterized by retinal ganglion cell death and nerve fiber layer atrophy. Several randomized controlled trials have consistently demonstrated the efficacy of intraocular pressure lowering to slow or halt the measurable progression of the disease. Medical therapy, in places where it is easily accessible, is often the primary method to lower intraocular pressure. We review the medical options currently available and possible future options currently in development. The 5 contemporary classes of topical agents in use include prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and cholinergics. In addition, several fixed combination agents are commercially available. Agents from each of these classes have unique mechanisms of action, adverse effects, and other characteristics that impact how they are used in clinical practice. Despite the plethora of medical options available, there are limitations to topical ophthalmic therapy such as the high rate of noncompliance and local and systemic adverse effects. Alternate and sustained drug delivery models, such as injectable agents and punctal plug delivery systems, may in the future alleviate some such concerns and lead to increased efficacy of treatment while minimizing adverse effects. PMID- 26886121 TI - Management of Primary Angle-Closure Glaucoma. AB - Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic enlargement of optic disc cupping and visual field loss that is secondary to ocular hypertension caused by closure of the drainage angle. Angle closure is caused by appositional approximation or adhesion between the iris and the trabecular meshwork. The main treatment strategy for PACG lies in the reduction of intraocular pressure, reopening of the closed angle, and possible prevention of further angle closure. There is no universally agreed best surgical treatment for PACG. Trabeculectomy, goniosynechialysis (GSL), glaucoma implant, and cyclodestructive procedures are effective surgical options. Each of them plays an important role in the management of PACG with its own pros and cons. Accumulating evidence is available to show the effectiveness of visually significant and visually nonsignificant cataract extraction in the treatment of PACG. Trabeculectomy and GSL are often combined with cataract extraction, which may offer additional pressure control benefits to patients with PACG. This review article will discuss laser peripheral iridotomy, argon laser peripheral iridoplasty, and surgeries such as GSL, phacoemulsification, and phaco plus glaucoma surgeries that lower intraocular pressure and also alter the anterior segment and/or drainage angle anatomy. Currently, glaucoma implants and cyclodestruction are mainly reserved for PACG patients who have failed previous filtering operations. Their role as initial surgical treatment for PACG will not be discussed. PMID- 26886122 TI - Selective Laser Trabeculoplasty: An Update. AB - Selective laser trabeculoplasty (SLT) is an effective treatment option for the reduction of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. The mechanism by which SLT lowers IOP is not completely understood and is likely multifactorial. Published studies indicate that SLT is at least as effective as argon laser trabeculoplasty or medications at lowering IOP in many forms of glaucoma. In addition to IOP reduction, SLT may decrease IOP fluctuation and can be successfully used as primary or adjunctive therapy for the management of both early and advanced glaucoma. However, SLT may not be effective in certain forms of glaucoma, and the IOP-lowering effect seems to wane with time. High pretreatment IOP is the strongest predictor of treatment success, even in patients with normal-tension glaucoma. Repeatability of SLT has been controversial, but recent evidence suggests that it can be successfully repeated to achieve additional or recurrent IOP reduction, even in eyes that only had a modest response to initial treatment. Adverse events are uncommon after SLT, and the most common complications such as discomfort and inflammation are typically mild and transient. Further investigation is required to determine the optimal treatment parameters for SLT treatment. Limited evidence suggests that SLT is cost-effective as primary therapy for patients with glaucoma. PMID- 26886124 TI - Updates on the Surgical Management of Pediatric Glaucoma. AB - Childhood glaucoma is known to be one of the most challenging conditions to manage. Surgical management is more complicated than in adults because of differences in anatomy from adults along with variations in anatomy caused by congenital and developmental anomalies, wide-ranging pathogenetic mechanisms, a more aggressive healing response, and a less predictable postoperative course. Challenges in postoperative examination and management in less cooperative children and the longer life expectancies preempting the need for future surgeries and reinterventions are also contributing factors. Angle surgery is usually the first-line treatment in the surgical management of primary congenital glaucoma because it has a relatively good success rate with a low complication rate. After failed angle surgery or in cases of secondary pediatric glaucoma, options such as trabeculectomy, glaucoma drainage devices, or cyclodestructive procedures can be considered, depending on several factors such as the type of glaucoma, age of the patient, and the severity and prognosis of the disease. Various combinations of these techniques have also been studied, in particular combined trabeculotomy-trabeculectomy, which has been shown to be successful in patients with moderate-to-advanced disease. Newer nonpenetrating techniques, such as viscocanalostomy and deep sclerectomy, have been reported in some studies with variable results. Further studies are needed to evaluate these newer surgical techniques, including the use of modern minimally invasive glaucoma surgeries, in this special and diverse group of young patients. PMID- 26886123 TI - Lowering of Intraocular Pressure After Phacoemulsification in Primary Open-Angle and Angle-Closure Glaucoma: A Bayesian Analysis. AB - Phacoemulsification as treatment for primary open-angle glaucoma (POAG) remains more controversial than for primary angle-closure glaucoma (PACG). If the objective of glaucoma surgery is an additional greater than or equal to 5 to 6 mm Hg reduction of intraocular pressure (IOP), the role of phacoemulsification should be based on the probability of achieving this. A Bayesian analysis of available data was performed to calculate the change in IOP after phacoemulsification in POAG and PACG. Standard meta-analysis formulation with prephacoemulsification and postphacoemulsification IOP-assumed to have normal distributions, with study-specific means and SDs-was used. Absolute and relative change in IOP was calculated using different priors, and sensitivity analyses were performed. The prior that just included a decrease of greater than or equal to 6 mm Hg in the 95% credible interval was identified. The probability of achieving greater than or equal to 5 to 6 mm Hg decrease in IOP (and other levels) was calculated. Depending on the prior, the probability of achieving a greater than or equal to 5 mm Hg reduction in IOP in POAG varied from 0.1% to 3%. Confidence in a greater than or equal to 6 mm Hg decrease required a prior belief that phacoemulsification produces a mean decrease of 7 mm Hg. The probability of a decrease in IOP was greater in PACG: approximately 50% probability of a greater than or equal to 5 mm Hg decrease in PACG uncontrolled on medications. Phacoemulsification in POAG has a high probability of producing a small decrease in IOP that may be useful in early, well-controlled disease. The probability of a clinically significant decrease of greater than or equal to 5 to 6 mm Hg-required for advanced/uncontrolled disease-is low. Results support the role of phacoemulsification in PACG. PMID- 26886125 TI - A Balance between Nuclear and Cytoplasmic Volumes Controls Spindle Length. AB - Proper assembly of the spindle apparatus is crucially important for faithful chromosome segregation during anaphase. Thanks to the effort over the last decades, we have very detailed information about many events leading to spindle assembly and chromosome segregation, however we still do not understand certain aspects, including, for example, spindle length control. When tight regulation of spindle size is lost, chromosome segregation errors emerge. Currently, there are several hypotheses trying to explain the molecular mechanism of spindle length control. The number of kinetochores, activity of molecular rulers, intracellular gradients, cell size, limiting spindle components, and the balance of the spindle forces seem to contribute to spindle size regulation, however some of these mechanisms are likely specific to a particular cell type. In search for a general regulatory mechanism, in our study we focused on the role of cell size and nuclear to cytoplasmic ratio in this process. To this end, we used relatively large cells isolated from 2-cell mouse embryos. Our results showed that the spindle size upper limit is not reached in these cells and suggest that accurate control of spindle length requires balanced ratio between nuclear and cytoplasmic volumes. PMID- 26886126 TI - Temperature Insensitivity and Behavioural Reduction of the Physiological Stress Response to Longline Capture by the Gummy Shark, Mustelus antarcticus. AB - Many factors influence the physiological stress response to fisheries capture in elasmobranchs. However, the influence of sea surface temperatures (SST) and behaviour are unknown and crucial considering global fishing pressures. We investigated the effect of SST and behaviour on the physiological stress response to capture of the gummy shark, Mustelus antarcticus, and compared our results to a laboratory study using similar conditions to test whether stress responses of in situ capture are consistent with those from laboratory simulations. Capture time for 23 M. antarcticus ranged 32-241 min as measured by hook timers or time depth recorders (TDR) in SSTs ranging 12-20 degrees C. TDR data from 13 M. antarcticus were analysed to quantify capture behaviour as the percentage of time spent moving during capture. Several physiological variables measured from blood samples obtained immediately upon the animals' landing indicated that although warmer SSTs increased metabolic rate, the stress response to capture was not exacerbated by capture duration. During capture movement occurred for an average of 10% of the time and since M. antarcticus can respire whilst stationary, restricted movement probably mitigated potential influences of increased SSTs and capture duration on the stress response. Previous laboratory findings were also shown to be indicative of in situ conditions and we thus advise that studies control for water temperature given the influence it has on variables (e.g. lactate) used to measure capture stress in elasmobranchs. We highlight the importance of seasonal water temperatures and capture behaviour when assessing the resilience to fisheries capture and the implementation of appropriate fisheries management strategies. PMID- 26886127 TI - Ritonavir-boosted danoprevir-based regimens in treatment-naive and prior null responders with HCV genotype 1 or 4 and compensated cirrhosis. AB - BACKGROUND AND AIM: Effective and safe antiviral treatment regimens are needed for patients with chronic hepatitis C (CHC) and cirrhosis. METHODS: An international open-label trial was conducted in CHC patients with genotype (G)1/4 infection, compensated cirrhosis, HCV RNA >= 50,000 IU/mL and body mass index 18 35 kg/m(2). Treatment-naive patients (Cohort 1) received a triple therapy regimen [danoprevir/r 100/100 mg twice daily (bid), ribavirin 1000/1200 mg/day and peginterferon alfa-2a 180 ug/week] for 24 weeks. Prior null responders (Cohort 2) received a quadruple therapy regimen (danoprevir/r 100/100 mg bid, mericitabine 1000 mg bid and peginterferon alfa-2a/ribavirin). The primary efficacy outcome was sustained virological response (HCV RNA < limit of quantification, target not detected) at end of the 24-week follow-up period (SVR24). RESULTS: In Cohort 1 (n = 23), 73.9 and 65.2 % of patients had a virological response at Weeks 4 and 24, respectively; 39.1 % achieved SVR24 (G1a = 1/13; G1b = 8/9; G4 = 0/1). In Cohort 2 (n = 20), 100 % achieved virological response at Weeks 4 and 24; 65 % achieved SVR24 (G1a = 4/8; G1b = 7/10; G4 = 2/2). Treatment failure was more common in G1a than G1b-infected patients and less common in patients receiving quadruple therapy. Treatment failure was associated with emergence of resistance to danoprevir, but not mericitabine. The safety profile was typical of that associated with peginterferon alfa-2a/ribavirin. No deaths/episodes of hepatic decompensation occurred. CONCLUSIONS: Treatment with danoprevir/r-based regimens for 24 weeks is safe and well tolerated in CHC patients with compensated cirrhosis. A quadruple therapy regimen (danoprevir/r, mericitabine, peginterferon alfa/ribavirin) produced high SVR24 rates in prior null responders, particularly among G1b patients. PMID- 26886128 TI - The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis. AB - The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-kappaB (NF-kappaB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population. PMID- 26886129 TI - Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes. AB - PURPOSE: To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain). METHODS: This was a population based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73 m2 and/or urine albumin to creatinine ratio (UACR) >=30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy. RESULTS: CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4-1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values >=10 mg/g, and increased considerably with UACR values >=300 mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6-2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73 m2 [OR], 95% confidence interval [CI], 1.3 (1.1-1.6). CONCLUSIONS: These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population. PMID- 26886130 TI - Heterozygosity, gender, and the growth-defense trade-off in quaking aspen. AB - Although plant growth is generally recognized to be influenced by allocation to defense, genetic background (e.g., inbreeding), and gender, rarely have those factors been addressed collectively. In quaking aspen (Populus tremuloides Michx.), phenolic glycosides (PGs) and condensed tannins (CTs) constitute up to 30 % of leaf dry weight. To quantify the allocation cost of this chemical defense, we measured growth, defense chemistry, and individual heterozygosity (H obs at 16 microsatellite loci) for male and female trees in both controlled and natural environments. The controlled environment consisted of 12 juvenile genets grown for 3 years in a common garden, with replication. The natural environment consisted of 51 mature genets in wild populations, from which we sampled multiple ramets (trees) per genet. Concentrations of PGs and CTs were negatively correlated. PGs were uncorrelated with growth, but CT production represented a major cost. Across the range of CT levels found in wild-grown trees, growth rates varied by 2.6-fold, such that a 10 % increase in CT concentration occurred with a 38.5 % decrease in growth. H obs had a marked effect on aspen growth: for wild trees, a 10 % increase in H obs corresponded to a 12.5 % increase in growth. In wild trees, this CT effect was significant only in females, in which reproduction seems to exacerbate the cost of defense, while the H obs effect was significant only in males. Despite the lower growth rate of low-H obs trees, their higher CT levels may improve survival, which could account for the deficit of heterozygotes repeatedly found in natural aspen populations. PMID- 26886131 TI - The effect of timing of growing season drought on flowering of a dominant C4 grass. AB - Timing of precipitation is equally important as amount for determining ecosystem function, especially aboveground net primary productivity (ANPP), in a number of ecosystems. In tallgrass prairie of the Central Plains of North America, grass flowering stalks of dominant C4 grasses, such as Andropogon gerardii, can account for more than 70 % of ANPP, or almost none of it, as the number of flowering stalks produced is highly variable. Although growing season precipitation amount is important for driving variation in flowering stalk production, it remains unknown whether there are critical periods within the growing season in which sufficient rainfall must occur to allow for flowering. The effect of timing of rainfall deficit (drought) on flowering of A. gerardii, was tested by excluding rainfall during three periods within the growing season (starting in mid-April, mid-May and mid-June). Mid-summer drought (starting in mid-June) strongly reduced the flowering rate (e.g., density and biomass) of A. gerardii (e.g., as high as 94 % compared to the control), suggesting flowering is highly sensitive to precipitation at this time. This effect appeared to be related to plant water status at the time of flowering stalk initiation, rather than an indirect consequence of reduced C assimilation. Our results suggest that increased frequency of growing season drought forecast with climate change could reduce sexual reproduction in this dominant grass species, particularly if it coincides with timing of flowering stalk initiation, with important implications for ecosystem functioning. PMID- 26886133 TI - [Kidney tumours]. PMID- 26886132 TI - The effect of dietary cricket meal (Gryllus bimaculatus) on growth performance, antioxidant enzyme activities, and haematological response of African catfish (Clarias gariepinus). AB - This study was conducted to investigate the growth performance, biomarkers of oxidative stress, catalase (CAT), superoxide dismutase (SOD), and glutathione S transferase (GST) as well as the haematological response of African catfish after being fed with fish feed containing different levels of cricket meal. The juvenile fish were assigned to three different treatments with isonitrogenous (35 %) and isoenergetic (19 kJ g(-1)) diets containing 100 % cricket meal (100 % CM), 75 % cricket meal (75 % CM), and 100 % fishmeal (100 % FM) as control groups for 7 weeks. The results indicated that a diet containing 100 % CM and 75 % CM improved growth performance in terms of body weight gain and specific growth rate, when compared to 100 % FM. The feed conversion ratio (FCR) and protein efficiency ratio (PER) did not differ significantly between all diets, but reduced FCR and increased PER were observed with a higher inclusion of cricket meal. A haematological examination of fish demonstrated no significant difference of red blood cells in all diets and white blood cells showed a significantly higher value in fishmeal-fed fish. On the other hand, haemoglobin and haematocrit significantly increased with increasing amounts of cricket meal in the diet. Antioxidant activity of CAT was higher in the 100 % CM group compared to fish fed other diets, whereas GST and SOD showed increasing trends with a higher incorporation of cricket, although insignificant differences were observed between all diets. These results suggest that cricket meal could be an alternative to fishmeal as a protein source in the African catfish diet. PMID- 26886135 TI - Two-Drug Treatment Approaches in HIV: Finally Getting Somewhere? AB - The advent of combination antiretroviral therapy (ART) has significantly decreased AIDS-related morbidity and mortality. Nevertheless, the benefits of ART are only realized through adherence to lifelong treatment. Though contemporary antiretroviral (ARV) drugs have fewer adverse effects in comparison to older ARV drugs, many agents are associated with negative or unknown long-term effects. There is increasing evidence that two-drug (dual-therapy) regimens may be an effective alternative to the currently recommended three-drug (triple-therapy) regimens. In this review, we provide a comprehensive and critical review of recently completed and ongoing trials of dual-therapy regimens in treatment-naive and treatment-experienced HIV-1-infected patients. We also review current HIV/AIDS society recommendations regarding dual therapy as well as future therapeutic possibilities. PMID- 26886134 TI - Thyroid Hormone Mimetics: the Past, Current Status and Future Challenges. AB - The association between thyroid hormone status and plasma levels of low-density lipoprotein cholesterol has raised the awareness for the development of thyroid hormone mimetics as lipid-lowering agents. The discovery of the two main types of thyroid hormone receptors (alpha and beta) as well as the development of novel combinatorial chemistry providing organ specificity has drastically improved the selectivity of these compounds. In the past decades, several thyroid hormone mimetics have been investigated with the purpose of lowering low-density lipoprotein cholesterol levels. However, until now, none of the thyromimetics reached the stage of completing a phase III clinical trial without deleterious side effects. Here, we review the currently available literature on thyromimetics investigated for the treatment of dyslipidemia, their rise, their downfall and the challenges for the development of novel agents. PMID- 26886137 TI - Right Ventricular Function in Infants with Bronchopulmonary Dysplasia: Association with Respiratory Sequelae. AB - BACKGROUND: While cor pulmonale has been noted in infants with bronchopulmonary dysplasia (BPD), information on right ventricular (RV) function is limited. OBJECTIVE: To assess RV function in infants with severe BPD and ascertain correlation with respiratory outcomes. METHODS: We prospectively assessed RV function using tissue Doppler imaging (TDI), 2D fractional area change (FAC), M mode tricuspid annular plane systolic excursion (TAPSE) and myocardial performance index (MPI) using echocardiography. Additionally, we compared RV function with preterm infants with no BPD. RESULTS: Eighteen preterm infants with severe BPD were enrolled at 36 weeks' gestation. Higher E/E' (r = 0.78, p < 0.0001) and lower FAC (r = 0.8, p < 0.0001) showed strong correlations with the subsequent duration of respiratory support. Correlations with TDI isovolumic velocity and Tei index were significant (-0.69, p = 0.002 and 0.58, p = 0.011, respectively). On comparison with infants with no BPD, TDI peak systolic velocities (0.06 +/- 0.01 vs. 0.09 +/- 0.01 m/s, p < 0.0001), peak isovolumic systolic velocities (0.05 +/- 0.009 vs. 0.07 +/- 0.008 m/s, p < 0.0001) and RV FAC (31 +/- 4.7 vs. 36 +/- 3.6%, p = 0.019) were significantly lower. Cardiac relaxation was impaired [higher TDI E/E' ratio (9.6 +/- 1.8 vs. 5.2 +/- 0.5, p < 0.0001) and higher RV MPI (0.33 +/- 0.03 vs. 0.25 +/- 0.03, p < 0.0001)]. CONCLUSIONS: Impaired RV performance in the infants with severe BPD at 36 weeks' corrected gestation correlated with a longer duration of subsequent respiratory support. PMID- 26886136 TI - Duration of gonorrhoea and chlamydia infection at the pharynx and rectum among men who have sex with men: a systematic review. AB - Background Chlamydia and gonorrhoea are the two most common sexually transmissible infections (STI) among men who have sex with men (MSM) worldwide. Infections at the pharynx and rectum are usually asymptomatic; however, the natural history of these infections remains unknown. The aim of this study is to estimate the duration of both infections at the extragenital sites from published epidemiological cohort studies. METHODS: English peer-reviewed articles were searched from 1 January 2000 to 12 March 2015 in three electronic databases (MEDLINE, EMBASE and Cochrane Central). The prevalence-to-incidence ratio from each study was calculated to reflect the duration of each infection. This review followed the PRISMA guidelines and was registered in PROSPERO (CRD42014007087). RESULTS: There were 2585 records identified, with 1721 abstracts and 52 full-text articles screened, resulting in four studies fulfilling the inclusion criteria. Pharyngeal gonorrhoea (114-138 days) had a shorter duration of infection than rectal gonorrhoea (346 days). In addition, chlamydia had a longer duration of infection at the pharynx (667 days) and rectum (579 days) compared with gonorrhoea infection. CONCLUSIONS: Gonorrhoea has a shorter duration of infection than chlamydia, suggesting that annual STI screening will be more effective at diagnosing chlamydia than gonorrhoea. The current STI guidelines recommend screening gonorrhoea and chlamydia at least once a year in MSM; it would only detect ~30% of incident pharyngeal gonorrhoea cases, with a mean duration of 4 months. PMID- 26886138 TI - Identifying optimal heparin management during cardiopulmonary bypass in obese patients: A prospective observational comparative study. AB - BACKGROUND: The heparin regimen providing anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW), but may be inaccurate in obese patients in whom TBW exceeds their ideal body weight. OBJECTIVES: The objective is to compare the effects of heparin injection based on TBW on haemostatic parameters between obese and nonobese patients during cardiac surgery and to calculate the optimal heparin regimen. DESIGN: Prospective comparative study. SETTING: University hospital. PATIENTS: Two groups of 50 patients (BMI>= or <30 kg m) were included in the study over a 9-month period in 2013. The study started on 27 February 2013. INTERVENTIONS: An unfractionated heparin (UFH) bolus of 300 IU kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU kg) to maintain a target activated coagulation time (ACT) of at least 400 s. MAIN OUTCOME MEASURES: ACT and plasma heparin concentration were measured at different time points after initiation of, and weaning from CPB. RESULTS: Obese patients received higher initial and total doses of heparin (P < 0.0001). Plasma heparin concentrations were significantly higher in obese patients at each time point (P < 0.001) and reached very high values after the initial bolus (5.90 vs. 4.48 IU ml, P < 0.0001). The relationship between plasma heparin concentration and ACT after the initial bolus was not linear and followed an asymptotic regression curve. Haemoglobin concentration decreased intraoperatively to a greater extent in the obese group (P < 0.001). No significant differences in postoperative bleeding or global transfusion requirements were observed. CONCLUSION: The standard heparin regimen based on TBW in obese patients during CPB results in excessive plasma heparin concentrations and a significant intraoperative decrease in haemoglobin concentration. ACT monitoring was not accurate in identifying this excess dosage. An initial bolus of 340 IU kg ideal body weight would achieve a heparin concentration of 4.5 IU ml, similar to that observed in nonobese patients. Further investigations are warranted to confirm this heparin regimen. PMID- 26886139 TI - Acromio-axillo-suprasternal notch index: a new screening test to predict difficult laryngoscopy in obstetric patients scheduled for caesarean delivery. PMID- 26886140 TI - Use of rocuronium and sugammadex in renal transplantation: Problems that must be considered. PMID- 26886141 TI - [Intensive care treatment of a patient with Ebola virus disease in Germany]. AB - In this case report, we describe the clinical course of a patient with Ebola virus disease who was transferred to the Highly Contagious Pathogens Treatment Unit at the Hamburg University Medical Center. High volume turnover, electrolyte imbalances, paralytic ileus, sepsis with multiresistant gram-negative pathogen, and respiratory failure due to blood aspiration were major clinical challenges. PMID- 26886142 TI - Bisphosphonate use and lower risk of incident diabetes mellitus: suggestions for other possible explanations. PMID- 26886143 TI - Mediation of Developmental Risk Factors for Psychosis by White Matter Microstructure in Young Adults With Psychotic Experiences. AB - IMPORTANCE: White matter (WM) abnormalities have been identified in schizophrenia at the earliest stages of the disorder. Individuals in the general population with psychotic experiences (PEs) may show similar changes, suggesting dysfunction due to aberrant neurodevelopment. Studying such people is a powerful means of understanding the nature of neurodevelopmental problems without the confound of clinical management and allows other potential risk factors associated with the schizophrenia spectrum to be taken into account. OBJECTIVES: To compare WM microstructure and myelination in young adults with and without PEs identified from a population-based cohort using diffusion and relaxometry magnetic resonance imaging and to quantify potential mediating effects of WM on several known risk factors for psychosis. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, participants were drawn from the UK Avon Longitudinal Study of Parents and Children. Psychotic experiences were assessed using a semistructured interview. Magnetic resonance imaging was carried out at age 20 years in 123 participants who had PEs and 124 individuals serving as controls. Participants with PEs were subdivided into those with operationally defined suspected PEs, definite PEs, and psychotic disorder. MAIN OUTCOMES AND MEASURES: Diffusion tensor magnetic resonance imaging and relaxometry-derived myelin water fractions were used to measure WM microstructure and myelination, respectively. Differences in quantitative WM indices were assessed using tract-based spatial statistics. A binary model and a continuum-like ordinal model of PEs were tested. RESULTS: Among the 123 participants who had PEs (mean [SE] age, 20.01 [0.004] years), 37 were male and 86 were female. Among the 124 controls (mean [SE] age, 20.11 [0.004] years), 49 were male and 76 were female. Fractional anisotropy in left frontomedial WM was significantly reduced in individuals with PEs (Montreal Neurological Institute [MNI] coordinates, -18, 37, -2; P = .0046). The ordinal model identified a similar but more widespread effect, with a corresponding increase in radial diffusivity (MNI coordinates, -15, 29, 21; P = .0042). Low birth weight (rho = -0.155; P = .015) and childhood IQ (rho = -0.188; P = .003) were associated with the presence of PEs. Results of mediation analysis were consistent with the association between birth weight (21.1% mediation effect; P = 6.20 * 10-3) and childhood IQ (7.9% mediation effect; P = .041) and by PEs being mediated by fractional anisotropy changes in these regions. CONCLUSIONS AND RELEVANCE: The results of the study imply the presence of abnormal WM microstructure in young adults with PEs. The results are consistent with the hypothesis that neurodevelopmental factors cause alterations in the cellular composition of WM circuits critical to higher cognitive function. Such alterations may first manifest in childhood as reduced IQ and later contribute to PEs in early adulthood. PMID- 26886144 TI - Muscle strengthening activities and mortality with considerations by hearing sensitivity. AB - OBJECTIVE: Research demonstrates that hearing impairment is associated with premature all-cause mortality. Emerging work indicates that physical activity is associated with hearing sensitivity and muscle strengthening activities (MSA) are favorably associated mortality in the general population. Whether MSA can promote survival among those with hearing impairment is, at this point, unknown, which was this study's objective. DESIGN: Prospective cohort study using data from the 2003-2006 National Health and Nutrition Examination Survey, with follow-up through 2011. STUDY SAMPLE: 1482 adult (20-85 years) participants comprised the analytic sample. RESULTS: Among the study participants, 152 died over the follow up period (10.26%; unweighted); the unweighted median follow-up period was 89 months (IQR = 74-98 months). Among adults with moderate or greater hearing loss who achieved the United States Department of Health and Human Services guidelines for MSA (2 + sessions/week), they were at a 71% reduced risk of all-cause mortality (HRadjusted = 0.29; 95% CI: 0.10-0.83; P = 0.02). CONCLUSIONS: MSA may help to prolong survival among those with worse hearing impairment. PMID- 26886145 TI - Maternal and Neonatal Outcomes of Preterm Premature Rupture of Membranes before Viability. AB - BACKGROUND: To investigate maternal and neonatal outcomes of previable preterm premature rupture of membranes (PPROM) and compare outcome between previable PPROM before and after 20 weeks of pregnancy, with data from one single center. PATIENTS: All women with singleton or twin pregnancies, from 2002 through 2011, who presented with PPROM before 24 weeks of gestation. METHOD: A retrospective cohort study in a university teaching hospital in the Netherlands. Data were analyzed and compared between pregnancies with previable PPROM before and after 20 weeks of pregnancy. Main outcome measures were maternal and neonatal morbidity and mortality. RESULTS: A total of 160 women (164 fetuses) were included. 90 women (56.2%) developed complications (intra-uterine infection, retained placenta, placental abruption or sepsis). There was no maternal mortality. 68 neonates were admitted after birth. PPHN (64.7%, p=0.001) and contractures (58.8%, p<0.001) occurred significantly more in neonates born after PPROM<20 weeks of pregnancy. Eventually 38.4% of the neonates survived. Neonates born after previable PPROM > 20 weeks had a greater likelihood of being alive at discharge (22.7 vs. 46.9%, p=0.008). DISCUSSION: This study of previable PPROM shows that more than 50% of the mothers develop one or more complications. Neonates have a high mortality rate, especially neonates born after PPROM<20 weeks of pregnancy. In particular neonates born after PPROM<20 weeks of pregnancy should be watched closely for PPHN and contractures. CONCLUSION: This large single center study can provide good foundation for counseling parents on previable PPROM, especially the prognosis of PPROM<20 weeks of pregnancy is of additional value. PMID- 26886146 TI - [Utilization of Occupational Therapy in Children - Results from the KiGGS Basis Survey]. AB - BACKGROUND: A population-based analysis on use of occupational therapy by child's parentally reported health restrictions and socio-demographic determinants is missing. PATIENTS AND METHODS: The basis KiGGS survey (2003 to 2006) reports on health in 17 641 children aged 0 to 17 years. The use of occupational therapy in the last 12 months could be ticked as other therapies with a free text field to name occupational therapy or others. Health restrictions potentially relevant for the use of occupational therapy and sociodemographic factors were assessed. The proportion of use of occupational therapy explained by the health restrictions was estimated by the population attributable risk fraction. RESULTS: The average use of occupational therapy for 3 to 13-year-olds was 2.4%. There was no association with the socioeconomic status; Children with immigration background used occupational therapy less often (e. g. age group 3 to 6 years: ORadjusted 0.2 [95-% KI: 0.1-1.0]). The proportion of occupational therapy explainable by the health restrictions considered ranged from 45% (3 to 6 years) to 65% (11 to 13 years). DISCUSSION: The lower use of occupational therapy in the KiGGS survey compared to health insurance reports may be explained by the ascertainment method. A lower use of occupational therapy related to immigration background matches lower use for physician visits. CONCLUSION: The causes for the low proportion of explained occupational therapy in young children and the lower use in children with immigration background warrant further research. PMID- 26886147 TI - Sequence Variants of SIRT6 Gene Promoter in Myocardial Infarction. AB - AIMS: Coronary artery disease (CAD), including myocardial infarction (MI), is a common complex disease caused by atherosclerosis. Although more than 50 genetic variants have been associated with CAD, these loci collectively account for only 10% of CAD cases. Genetic variants of low and rare frequencies have been proposed as the main causes of CAD. SIRT6, one of the highly conserved NAD-dependent class III deacetylases, has been implicated in cardiovascular diseases. Considering the important roles that SIRT6 plays in the cardiovascular system, inflammation, and lipid and cholesterol metabolism, genetic variants were hypothesized to contribute to MI development. METHODS: The promoter regions of the SIRT6 gene were genetically analyzed in large cohorts of MI patients (n = 371) and ethnically-matched controls (n = 383). RESULTS: A total of 15 DNA sequence variants (DSVs) were identified, including seven single-nucleotide polymorphisms (SNPs). Two novel heterozygous DSVs, g.4183823G>C and g.4183742G>A, were identified in two MI patients but in none of the controls. Two SNPs, g.4183685T>C (rs4359565) and g.4182942C>A (rs3760905), were found in MI patients with significantly higher frequencies compared with controls. CONCLUSIONS: These DSVs identified in MI patients may alter the transcriptional activity of the SIRT6 gene promoter and alter SIRT6 levels which might contribute to the risk of MI. PMID- 26886148 TI - Serotonergic drugs for the treatment of neuropsychiatric symptoms in dementia. AB - Behavioral and psychological symptoms of dementia (known also as neuropsychiatric symptoms) are essential features of Alzheimer's disease and related dementias. The near universal presence of neuropsychiatric symptoms in dementia (up to 90% of cases) has brought significant attention of clinicians and experts to the field. Non-pharmacological and pharmacological interventions are recommended for various types of neuropsychiatric symptoms. However, most pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia are used off-label in many countries. Cognitive decline and neuropsychiatric symptoms can be linked to alterations in multiple neurotransmitter systems, so modification of abnormalities in specific systems may improve clinical status of patients with neuropsychiatric symptoms. Use of serotonergic compounds (novel particles acting on specific receptors and widely acting drugs) in the treatment of neuropsychiatric symptoms is reviewed. PMID- 26886149 TI - Zero-Dimensional Hybrid Organic-Inorganic Halide Perovskite Modeling: Insights from First Principles. AB - We discuss the properties of zero dimensional (cluster) hybrid organic-inorganic halide perovskite in view of their possible applicability in photovoltaics, light emitting, and lasing devices. To support the need of theoretical investigations of such systems and pave the way for future investigations of clusters with different orientations, terminations, and compositions, we have assembled and characterized some zero dimensional models of methylammonium lead iodide, MAPbI3, by "cutting" its bulk. Interesting properties of such clusters that have been here theoretically investigated include their charge distribution, bandgap, wave function localization, and reduced effective mass. The surface orientation/termination and the organic/inorganic cation ratios have been discussed together with the roles they play in determining the electronic properties of such clusters. Also in agreement with experiments, it emerges that surface termination is crucial in determining the structural and optoelectronic properties of this largely overlooked, dimensionally reduced class of materials. Analogies and differences between clusters and bulk are discussed. PMID- 26886150 TI - Lattice Defects in the Kitaev Honeycomb Model. AB - The Kitaev honeycomb lattice system is an important model of topological materials whose phase diagram exhibits both abelian and non-abelian topological phases. The latter, a so-called Ising phase, is related to topological superconductors. Its quasiparticle excitations, which are formed by Majorana fermions attached to vortices, show non-abelian fractional statistics and are known as Ising anyons. We investigate dislocation defects in the Ising phase of the Kitaev honeycomb model. After introducing them to the system, we accordingly generalize our solution of this model to the situation with the defects. The important part of this effort is developing an appropriate Jordan-Wigner fermionization procedure. It is expected that the presence of defects manifests itself by the formation of fermionic zero-energy modes around the defect end points. We numerically confirm this expectation and further investigate properties of these modes. The computational potential of our technique is demonstrated for both diagonalization and dynamical simulations. The latter focuses on the process of fusion of the vortex zero-energy modes with the Majorana fermions attached to the defect. This process simulates fusion of non abelian Ising anyons. PMID- 26886151 TI - When I'm 64: Effects of an interdisciplinary gerontology course on first-year undergraduates' perceptions of aging. AB - One challenge for gerontology is getting more students interested in aging at an earlier point in their academic career. This study evaluated the impact of an interdisciplinary course on aging designed for first-year undergraduate students. The course aimed to expand students' appreciation of the personal and professional relevance of aging issues, with the goal of expanding their aging related curricular and career interests. Main outcome variables of the study included knowledge of older adults and aging, attitudes toward older adults, and anxiety about personal aging. Participants included an intervention group enrolled in the course and a control group not enrolled in the course. Compared to baseline, at the end of the semester students in the class had more knowledge about aging and more positive explicit attitudes toward older adults, but their implicit attitudes toward older adults and anxiety about aging did not change. Control students showed no changes. These findings suggest that objective knowledge of aging and explicit attitudes improve with curricular intervention, but implicit attitudes and anxiety might be more difficult to change. Gerontology education is a complex undertaking whose diverse goals must be clearly articulated in order to guide curricular interventions and incite curiosity among young undergraduate students. PMID- 26886152 TI - Need for cognition moderates paranormal beliefs and magical ideation in inconsistent-handers. AB - A growing literature suggests that degree of handedness predicts gullibility and magical ideation. Inconsistent-handers (people who use their non-dominant hand for at least one common manual activity) report more magical ideation and are more gullible. The current study tested whether this effect is moderated by need for cognition. One hundred eighteen university students completed questionnaires assessing handedness, self-reported paranormal beliefs, and self-reported need for cognition. Handedness (Inconsistent vs. Consistent Right) and Need for Cognition (High vs. Low) were treated as categorical predictors. Both paranormal beliefs and magical ideation served as dependent variable's in separate analyses. Neither set of tests yielded main effects for handedness or need for cognition. However, there were a significant handedness by need for cognition interactions. Post-hoc comparisons revealed that low, but not high, need for cognition inconsistent-handers reported relatively elevated levels of paranormal belief and magical ideation. A secondary set of tests treating the predictor variables as continuous instead of categorical obtained the same overall pattern. PMID- 26886153 TI - Electron Solvation in Liquid Ammonia: Lithium, Sodium, Magnesium, and Calcium as Electron Sources. AB - A free electron in solution, known as a solvated electron, is the smallest possible anion. Alkali and alkaline earth atoms serve as electron donors in solvents that mediate outer-sphere electron transfer. We report herein ab initio molecular dynamics simulations of lithium, sodium, magnesium, and calcium in liquid ammonia at 250 K. By analyzing the electronic properties and the ionic and solvation structures and dynamics, we systematically characterize these metals as electron donors and ammonia molecules as electron acceptors. We show that the solvated metal strongly modifies the properties of its solvation shells and that the observed effect is metal-specific. Specifically, the radius and charge exhibit major impacts. The single solvated electron present in the alkali metal systems is distributed more uniformly among the solvent molecules of each metal's two solvation shells. In contrast, alkaline earth metals favor a less uniform distribution of the electron density. Alkali and alkaline earth atoms are coordinated by four and six NH3 molecules, respectively. The smaller atoms, Li and Mg, are stronger electron donors than Na and Ca. This result is surprising, as smaller atoms in a column of the periodic table have higher ionization potentials. However, it can be explained by stronger electron donor-acceptor interactions between the smaller atoms and the solvent molecules. The structure of the first solvation shell is sharpest for Mg, which has a large charge and a small radius. Solvation is weakest for Na, which has a small charge and a large radius. Weak solvation leads to rapid dynamics, as reflected in the diffusion coefficients of NH3 molecules of the first two solvation shells and the Na atom. The properties of the solvated electrons established in the present study are important for radiation chemistry, synthetic chemistry, condensed-matter charge transfer, and energy sources. PMID- 26886154 TI - Efficacy of belimumab and targeting of rheumatoid factor-positive B-cell expansion in Sjogren's syndrome: follow-up after the end of the phase II open label BELISS study. AB - OBJECTIVES: Belimumab, a monoclonal anti-B lymphocyte Stimulator (BLyS) antibody, appeared effective in Sjogren's syndrome (SS) in the phase II open-label 52-week BELISS study. Herein, the follow-up after the end of the BELISS study and suspension of the drug was reported in order to further verify the efficacy of belimumab in SS. METHODS: 13 SS patients were followed after the end of the belimumab treatment. The patients were all female, aged 54+/-15 years; all the patients presented anti-SSA and/or anti-SSB positivity. Composite scores for SS disease activity were collected at month 6 and month 12 after the end of the trial. The changes of IgG, IgA, IgM immunoglobulin serum levels, and rheumatoid factor (RF) level were reported. BLyS serum levels were also analysed. Statistics for paired comparisons were used. RESULTS: ESSDAI score increased from 3.5+/-3.7 at week 52 (end of the trial) to 7.0+/-5.7 at month 12 after the end of the trial (p=0.003). RF level increased from 31.0 (8.0-224.6) IU/ml at week 52 to 69 (11 666) IU/ml at month 12 after the end of the trial (p=0.008). IgM level increased from 131.9+/-73.6 mg/dl at week 52 to 165+/-84.6 mg/dl at month 12 after the end of the trial (p=0.04). A significant increase of serum BLyS levels also increased from 1304 (667-3835) pg/ml at week 52 to 2882 (1353-6178) pg/ml twelve months after belimumab suspension (p=0,04). CONCLUSIONS: Targeting BLyS by belimumab appears effective in SS, with the inhibition of RF-positive B cell proliferation. PMID- 26886155 TI - Domestic violence against women in India: A systematic review of a decade of quantitative studies. AB - Domestic violence (DV) is prevalent among women in India and has been associated with poor mental and physical health. We performed a systematic review of 137 quantitative studies published in the prior decade that directly evaluated the DV experiences of Indian women to summarise the breadth of recent work and identify gaps in the literature. Among studies surveying at least two forms of abuse, a median 41% of women reported experiencing DV during their lifetime and 30% in the past year. We noted substantial inter-study variance in DV prevalence estimates, attributable in part to different study populations and settings, but also to a lack of standardisation, validation, and cultural adaptation of DV survey instruments. There was paucity of studies evaluating the DV experiences of women over age 50, residing in live-in relationships, same-sex relationships, tribal villages, and of women from the northern regions of India. Additionally, our review highlighted a gap in research evaluating the impact of DV on physical health. We conclude with a research agenda calling for additional qualitative and longitudinal quantitative studies to explore the DV correlates proposed by this quantitative literature to inform the development of a culturally tailored DV scale and prevention strategies. PMID- 26886157 TI - Drug-Resistance Strategies of Early Adolescents in Mexico: Gender Differences in the Influence of Drug Offers and Relationship to the Offeror. AB - To address increases in substance use among Mexican adolescents, particularly females, US prevention programs are being adapted to the Mexican cultural context. Understanding how responses to substance offers by Mexican adolescents are shaped by gender and relationships to those making offers is an important step in the adaptation process. Using data from Guadalajara, Mexico middle schools (N = 431), this pilot study tested for gender differences in the use of several drug resistance strategies commonly taught in US substance abuse prevention interventions. Results indicated that the drug-resistance strategies of Mexican early adolescents differ by gender, type of substance offered, and the youth's relationship to the offeror. Contrary to previous research on older Mexican adolescents, in this sample, females received more substance offers from age peers than males did, and employed a wider repertoire of drug-resistance strategies, including active strategies such as direct refusals. Gender differences in use of the strategies persisted after controlling for number of offers received. There were gender differences in the conditional effects of greater exposure to offers. A larger volume of alcohol and cigarette offers predicted females' use of direct strategies more strongly than for males, but less strongly than males for marijuana offers. Females' use of drug resistance strategies was more strongly associated with offers from family adults, siblings, and cousins, while males' use of strategies was predicted more strongly by offers from nonfamily adults. Interpretations and prevention implications are discussed in light of changing gender norms in Mexico and gendered patterns of substance use. PMID- 26886158 TI - Peering into the "black box" of education interventions and attitude change: Audience characteristics moderate the effectiveness...and then only toward specific targets. AB - To probe the inconsistent link between education and attitude change toward minority social groups, we conducted a field study that focused on audience characteristics and education about lesbian, gay, and transgender (LGT) targets. Participants enrolled in a sexuality course were compared to those in a neurology course, both taught by the same professor. Multiple regression analyses predicted attitude change toward LGT targets from social dominance orientation (SDO), right wing authoritarianism (RWA), ratings of professor's characteristics, SDO by course interaction, and RWA by course interaction. Only the SDO by course interaction significantly predicted attitude change. Simple slopes analyses indicated that high-SDO participants in the sexuality course showed the most positive attitude change. These findings suggest that education may reduce prejudice for certain audience characteristics. PMID- 26886156 TI - Effect of Regional Hospital Competition and Hospital Financial Status on the Use of Robotic-Assisted Surgery. AB - IMPORTANCE: Despite the lack of efficacy data, robotic-assisted surgery has diffused rapidly into practice. Marketing to physicians, hospitals, and patients has been widespread, but how this marketing has contributed to the diffusion of the technology remains unknown. OBJECTIVE: To examine the effect of regional hospital competition and hospital financial status on the use of robotic-assisted surgery for 5 commonly performed procedures. DESIGN, SETTING, AND PARTICIPANTS: A cohort study of 221 637 patients who underwent radical prostatectomy, total nephrectomy, partial nephrectomy, hysterectomy, or oophorectomy at 1370 hospitals in the United States from January 1, 2010, to December 31, 2011, was conducted. The association between hospital competition, hospital financial status, and performance of robotic-assisted surgery was examined. MAIN OUTCOMES AND MEASURES: The association between hospital competition was measured with the Herfindahl Hirschman Index (HHI), hospital financial status was estimated as operating margin, and performance of robotic-assisted surgery was examined using multivariate mixed-effects regression models. RESULTS: We identified 221 637 patients who underwent one of the procedures of interest. The cohort included 30 345 patients who underwent radical prostatectomy; 20 802, total nephrectomy; 8060, partial nephrectomy; 134 985, hysterectomy; and 27 445, oophorectomy. Robotic-assisted operations were performed for 20 500 (67.6%) radical prostatectomies, 1405 (6.8%) total nephrectomies, 2759 (34.2%) partial nephrectomies, 14 047 (10.4%) hysterectomies, and 1782 (6.5%) oophorectomies. Use of robotic-assisted surgery increased for each procedure from January 2010 through December 2011. For all 5 operations, increased market competition (as measured by the HHI) was associated with increased use of robotic-assisted surgery. For prostatectomy, the risk ratios (95% CIs) for undergoing a robotic assisted procedure were 2.20 (1.50-3.24) at hospitals in moderately competitive markets and 2.64 (1.84-3.78) for highly competitive markets compared with noncompetitive markets. For hysterectomy, patients at hospitals in moderately (3.75 [2.26-6.25]) and highly (5.30; [3.27-8.57]) competitive markets were more likely to undergo a robotic-assisted surgery. Increased hospital profitability was associated with use of robotic-assisted surgery only for partial nephrectomy in facilities with medium-high (1.67 [1.13-2.48]) and high (1.50 [0.98-2.29]) operating margins. With analysis limited to patients treated at a hospital that had performed robotic-assisted surgery, there was no longer an association between competition and use of robotic-assisted surgery. CONCLUSIONS AND RELEVANCE: Patients undergoing surgery in a hospital in a competitive regional market were more likely to undergo a robotic-assisted procedure. These data imply that regional competition may influence a hospital's decision to acquire a surgical robot. PMID- 26886159 TI - Polycyclic aromatic hydrocarbons in Italian preserved food products in oil. AB - A method based on gas chromatography/ tandem mass spectrometry was used to assess levels of 16 EU priority polycyclic aromatic hydrocarbons (PAHs) in 48 preserved food products in oil including foods such as vegetables in oil, fish in oil and oil-based sauces obtained from the Italian market. The benzo[a]pyrene concentrations ranged from <0.04 to 0.40 ug kg(-1), and 72.9% of the samples showed detectable levels of this compound. The highest contamination level was observed for chrysene with three additional PAHs (benzo[a]anthracene, benzo[b]fluoranthene and benzo[c]fluorene) giving mean values higher than the mean value for benzo[a]pyrene. Chrysene was detected in all the samples at concentrations ranging from 0.07 to 1.80 ug kg(-1) (median 0.31 ug kg(-1)). The contamination expressed as PAH4 (sum of benzo(a)pyrene, chrysene, benzo(a)anthracene and benzo(b)fluoranthene), for which the maximum tolerable limit has been set by Commission Regulation (EU) No. 835/2011, varied between 0.10 and 2.94 ug kg(-1). PMID- 26886160 TI - The O-Carbamoyl-Transferase Alb15 Is Responsible for the Modification of Albicidin. AB - Albicidin is a potent antibiotic and phytotoxin produced by Xanthomonas albilineans which targets the plant and bacterial DNA gyrase. We now report on a new albicidin derivative which is carbamoylated at the N-terminal coumaric acid by the action of the ATP-dependent O-carbamoyltransferase Alb15, present in the albicidin (alb) gene cluster. Carbamoyl-albicidin was characterized by tandem mass spectrometry from cultures of a Xanthomonas overproducer strain and the gene function confirmed by gene inactivation of alb15 in X. albilineans. Expression of alb15 in Escherichia coli and in vitro reconstitution of the carbamoyltransferase activity confirmed albicidin as the substrate. The chemical synthesis of carbamoyl-albicidin finally enabled us to assess its bioactivity by means of in vitro gyrase inhibition and antibacterial assays. Compared to albicidin, carbamoyl-albicidin showed a significantly higher inhibitory efficiency against bacterial gyrase (~8 vs 49 nM), which identifies the carbamoyl group as an important structural feature of albicidin maturation. PMID- 26886161 TI - Genotype Specification Language. AB - We describe here the Genotype Specification Language (GSL), a language that facilitates the rapid design of large and complex DNA constructs used to engineer genomes. The GSL compiler implements a high-level language based on traditional genetic notation, as well as a set of low-level DNA manipulation primitives. The language allows facile incorporation of parts from a library of cloned DNA constructs and from the "natural" library of parts in fully sequenced and annotated genomes. GSL was designed to engage genetic engineers in their native language while providing a framework for higher level abstract tooling. To this end we define four language levels, Level 0 (literal DNA sequence) through Level 3, with increasing abstraction of part selection and construction paths. GSL targets an intermediate language based on DNA slices that translates efficiently into a wide range of final output formats, such as FASTA and GenBank, and includes formats that specify instructions and materials such as oligonucleotide primers to allow the physical construction of the GSL designs by individual strain engineers or an automated DNA assembly core facility. PMID- 26886162 TI - Switching long acting antipsychotic medications to aripiprazole long acting once a-month: expert consensus by a panel of Italian and Spanish psychiatrists. AB - INTRODUCTION: Aripiprazole long acting once-monthly (AOM) is a long acting atypical antipsychotic with proven efficacy in schizophrenia and with a pharmacological and a side effect profile that is different from other antipsychotics. These and other characteristics make AOM a possible alternative in patients requiring a change in long acting antipsychotic treatment due to issues such as lack of efficacy or persistent side effects. Both clinical and pharmacological factors should be considered when switching antipsychotics, and specific guidelines for long acting antipsychotic switching that address all these factors are needed. AREAS COVERED: A panel of Italian and Spanish experts in psychiatry met to discuss the strategies for the switch to AOM in patients with schizophrenia. Real life clinical experiences were shared and the clinical strategies to improve the likelihood of success were discussed. EXPERT OPINION: Due to its specific pharmacological and tolerability profile, AOM represents a suitable alternative for patients with schizophrenia requiring a switch to a new LAI treatment because of lack of efficacy or persistent side effects from another LAI. Possible strategies for the switch to AOM are presented in this expert consensus paper in an attempt to provide guidance throughout the entire switching process. PMID- 26886163 TI - Expert Study: Utility of an Automated Bolus Advisor System in Patients with Type 1 Diabetes Treated with Multiple Daily Injections of Insulin-A Crossover Study. AB - OBJECTIVE: This study was designed to assess the impact of the use of an automated bolus advisor (ABA) on glycemic control, quality of life, and satisfaction in adult patients with type 1 diabetes mellitus treated with multiple daily injections of insulin. MATERIALS AND METHODS: A crossover, prospective, randomized, controlled, multicenter study of 36 weeks duration was conducted. Patients were randomized to start in either control phase (CP) using a traditional blood glucose meter to calculate insulin doses (Accu-Chek((r)) Aviva Nano; Roche Diagnostics, Indianapolis, IN) or intervention phase (IP) using an ABA meter (Accu-Chek Aviva Expert; Roche Diagnostics) and switched to the other phase after a washout period. Each phase was 12 weeks in duration. RESULTS: Significant glycated hemoglobin (HbA1c) reduction was observed in both phases (CP, initial HbA1c of 8.05 +/- 0.7%, final HbA1c of 7.59 +/- 0.7% [P < 0.001]; IP, initial HbA1c of 8.13 +/- 1%, final HbA1c of 7.61 +/- 0.8% [P < 0.001]). Although the trend was to a higher HbA1c reduction in IP, no statistically significant differences were observed between phases (CP, HbA1c -0.39%; IP, HbA1c -0.52% [P = 0.8]). During IP, the number of daily glucose measurements was greater (4.28 +/- 1.2 vs. 4.01 +/- 1.1 [P < 0.006]), the rate of postprandial hypoglycemia was lower, and an improvement in quality of life and higher satisfaction were observed. CONCLUSIONS: In this first crossover study comparing the use of an ABA with the standard usual care, the use of an ABA was effective and well accepted. Furthermore, reduction in hypoglycemic events, improvement in adherence and quality of life, and higher treatment satisfaction were observed. PMID- 26886164 TI - Avian Influenza A(H5N1) Virus in Egypt. AB - In Egypt, avian influenza A subtype H5N1 and H9N2 viruses are enzootic in poultry. The control plan devised by veterinary authorities in Egypt to prevent infections in poultry focused mainly on vaccination and ultimately failed. Recently, widespread H5N1 infections in poultry and a substantial increase in the number of human cases of H5N1 infection were observed. We summarize surveillance data from 2009 through 2014 and show that avian influenza viruses are established in poultry in Egypt and are continuously evolving genetically and antigenically. We also discuss the epidemiology of human infection with avian influenza in Egypt and describe how the true burden of disease is underestimated. We discuss the failures of relying on vaccinating poultry as the sole intervention tool. We conclude by highlighting the key components that need to be included in a new strategy to control avian influenza infections in poultry and humans in Egypt. PMID- 26886165 TI - Altered lipid metabolism in the aging kidney identified by three layered omic analysis. AB - Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease. PMID- 26886168 TI - Correction: Membrane Partitioning of Anionic, Ligand-Coated Nanoparticles Is Accompanied by Ligand Snorkeling, Local Disordering, and Cholesterol Depletion. PMID- 26886167 TI - Surface Tension Guided Hanging-Drop: Producing Controllable 3D Spheroid of High Passaged Human Dermal Papilla Cells and Forming Inductive Microtissues for Hair Follicle Regeneration. AB - Human dermal papilla (DP) cells have been studied extensively when grown in the conventional monolayer. However, because of great deviation from the real in vivo three-dimensional (3D) environment, these two-dimensional (2D) grown cells tend to lose the hair-inducible capability during passaging. Hence, these 2D caused concerns have motivated the development of novel 3D culture techniques to produce cellular microtissues with suitable mimics. The hanging-drop approach is based on surface tension-based technique and the interaction between surface tension and gravity field that makes a convergence of liquid drops. This study used this technique in a converged drop to form cellular spheroids of dermal papilla cells. It leads to a controllable 3Dspheroid model for scalable fabrication of inductive DP microtissues. The optimal conditions for culturing high-passaged (P8) DP spheroids were determined first. Then, the morphological, histological and functional studies were performed. In addition, expressions of hair-inductive markers including alkaline phosphatase, alpha-smooth muscle actin and neural cell adhesion molecule were also analyzed by quantitative RT-PCR, immunostaining and immunoblotting. Finally, P8-DP microtissues were coimplanted with newborn mouse epidermal cells (EPCs) into nude mice. Our results indicated that the formation of 3D microtissues not only endowed P8-DP microtissues many similarities to primary DP, but also confer these microtissues an enhanced ability to induce hair follicle (HF) neogenesis in vivo. This model provides a potential to elucidate the native biology of human DP, and also shows the promising for the controllable and scalable production of inductive DP cells applied in future follicle regeneration. PMID- 26886166 TI - Germline and Somatic DICER1 Mutations in a Well-Differentiated Fetal Adenocarcinoma of the Lung. AB - Germ-line DICER1 mutations predispose to a distinctive tumour predisposition syndrome, the DICER1 syndrome, which is associated with a spectrum of rare mainly childhood-onset tumours. In 2014, a case of well-differentiated fetal adenocarcinoma of the lung (WDFA) was reported in a 16-year-old germ-line DICER1 mutation carrier. Here we report our finding of a characteristic somatic DICER1 RNase IIIb c.5127T>A (p.Asp1709Glu) missense mutation within the WDFA, confirmed using laser capture microscopy. The child has a personal history consistent with the DICER1 syndrome: she developed a multinodular goitre at age 14 years and an ovarian Sertoli-Leydig cell tumour at age 16 years, each of which were found to harbour a somatic DICER1 RNase IIIb missense mutation. The identification of two DICER1 "hits" in the WDFA strongly suggests that WDFA is a rare, previously unrecognised manifestation of DICER1 syndrome. PMID- 26886170 TI - Enhanced Uterine Contractility and Stillbirth in Mice Lacking G Protein-Coupled Receptor Kinase 6 (GRK6): Implications for Oxytocin Receptor Desensitization. AB - Oxytocin is a potent uterotonic agent and is used clinically for induction and augmentation of labor, as well as for prevention and treatment of postpartum hemorrhage. Oxytocin increases uterine contractility by activating the oxytocin receptor (OXTR), a member of the G protein-coupled receptor family, which is prone to molecular desensitization. After oxytocin binding, the OXTR is phosphorylated by a member of the G protein-coupled receptor kinase (GRK) family, which allows for recruitment of beta-arrestin, receptor internalization, and desensitization. According to previous in vitro analyses, desensitization of calcium signaling by the OXTR is mediated by GRK6. The objective of this study was to determine the role of GRK6 in mediating uterine contractility. Here, we demonstrate that uterine GRK6 levels increase in pregnancy and using a telemetry device to measure changes in uterine contractility in live mice during labor, show that mice lacking GRK6 produce a phenotype of enhanced uterine contractility during both spontaneous and oxytocin-induced labor compared with wild-type or GRK5 knockout mice. In addition, the observed enhanced contractility was associated with high rates of term stillbirth. Lastly, using a heterologous in vitro model, we show that beta-arrestin recruitment to the OXTR, which is necessary for homologous OXTR desensitization, is dependent on GRK6. Our findings suggest that GRK6-mediated OXTR desensitization in labor is necessary for normal uterine contractile patterns and optimal fetal outcome. PMID- 26886171 TI - Flavin-Containing Monooxygenase 3 Reduces Endoplasmic Reticulum Stress in Lipid Treated Hepatocytes. AB - Isoforms of flavin-containing monooxygenase (FMO) are involved in xenobiotic metabolism but have also been implicated in the regulation of glucose and lipid homeostasis and in the development of atherosclerosis. However, we have recently shown that improved insulin action is associated with increased FMO expression in livers of protein kinase C-deficient mice. Here, we investigated whether FMO3 expression affected insulin signaling, glucose metabolism, and endoplasmic reticulum (ER) stress in hepatocytes. HepG2 and IHH hepatocytes were transfected with FMO3 cDNA for overexpression, or small interfering RNA for knockdown. Cells were treated with palmitate to induce insulin resistance and insulin signaling, phosphoenolpyruvate carboxykinase (PEPCK) gene expression and ER stress markers were examined by immunoblotting and RT-PCR. Glycogen synthesis was measured using [(14)C]glucose. Palmitate treatment reduced insulin signaling at the level of Akt phosphorylation and glycogen synthesis, which were little affected by FMO3 overexpression. However, the fatty acid also increased the levels of several ER stress markers and activation of caspase 3, which were counteracted by FMO3 overexpression and exacerbated by FMO3 knockdown. Although FMO3 expression did not reverse lipid effects on protein thiol redox in hepatocytes, it did prevent up-regulation of the gluconeogenic enzyme PEPCK by pharmacological ER stress inducers or by palmitate. ER stress and PEPCK levels were also reduced in livers of fat-fed protein kinase Cdelta-deficient mice. Our data indicate that FMO3 can contribute to the regulation of glucose metabolism in the liver by reducing lipid induced ER stress and the expression of PEPCK, independently of insulin signal transduction. PMID- 26886173 TI - Ligand-Mediated Synthesis of Shape-Controlled Cesium Lead Halide Perovskite Nanocrystals via Reprecipitation Process at Room Temperature. AB - Colloidal nanocrystals of fully inorganic cesium lead halide (CsPbX3, X = Cl, Br, I, or combinations thereof) perovskites have attracted much attention for photonic and optoelectronic applications. Herein, we demonstrate a facile room temperature (e.g., 25 degrees C), ligand-mediated reprecipitation strategy for systematically manipulating the shape of CsPbX3 colloidal nanocrystals, such as spherical quantum dots, nanocubes, nanorods, and nanoplatelets. The colloidal spherical quantum dots of CsPbX3 were synthesized with photoluminescence (PL) quantum yield values up to >80%, and the corresponding PL emission peaks covering the visible range from 380 to 693 nm. Besides spherical quantum dots, the shape of CsPbX3 nanocrystals could be engineered into nanocubes, one-dimensional nanorods, and two-dimensional few-unit-cell-thick nanoplatelets with well-defined morphology by choosing different organic acid and amine ligands via the reprecipitation process. The shape-dependent PL decay lifetimes have been determined to be several to tens to hundreds of nanoseconds. Our method provides a facile and versatile route to rationally control the shape of the CsPbX3 perovskites nanocrystals, which will create opportunities for applications such as displays, lasing, light-emitting diodes, solar concentrators, and photon detection. PMID- 26886172 TI - Correlates of HIV and STI testing among Latino men who have sex with men in New York City. AB - We assessed the extent to which sociodemographic, personal, and behavioral factors are associated with human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing among a diverse group of Latino men who have sex with men (MSM) in New York City. The triangulation approach was used to synthesize data from 176 MSM who completed an in-person or phone questionnaire about substance use, alcohol consumption, sexual behaviors, and HIV/STI testing history and 40 participants who participated in focus groups. Correlates of testing significant in univariable analyses (p < .05) were entered into multivariable logistic regression models. Over half (57.9%) of study subjects tested for HIV in the previous 12 months and 60.2% tested for STIs in the previous 12 months. Age and education were positively correlated with HIV testing in multivariable analysis. No significant correlates of STI testing were identified. Spanish speaking only subjects were less likely to get tested for HIV and STI; however, this association was not significant. Our study demonstrates the need for further study of predictors of STI testing as well as the potential role of language barriers and education in routine testing for HIV. Social and behavioral factors may intensify these obstacles. Future research and interventions should address the role of language barriers and perceived issues of immigration status in the decision to get tested. PMID- 26886174 TI - Noncovalent Immobilization of a Molecular Iron-Based Electrocatalyst on Carbon Electrodes for Selective, Efficient CO2-to-CO Conversion in Water. AB - Catalysis of fuel-producing reactions can be transferred from homogeneous solution to surface via attachment of the molecular catalyst. A pyrene-appended iron triphenyl porphyrin bearing six pendant OH groups on the phenyl rings in all ortho and ortho' positions was immobilized on carbon nanotubes via noncovalent interactions and further deposited on glassy carbon. X-ray photoelectron spectroscopy and electrochemistry confirm catalyst immobilization. Using the carbon material, highly selective and rapid catalysis of the reduction of CO2 into CO occurs in water (pH 7.3) with 480 mV overpotential. Catalysis could be sustained for hours without loss of activity and selectivity, and high turnover number was obtained. PMID- 26886175 TI - Long-Range Antiferromagnetic Ordering in B-Site Ordered Double Perovskite Ca2ScOsO6. AB - A new Os-based B-site ordered double perovskite with the chemical composition of Ca2ScOsO6 was successfully synthesized. The crystal structure of the title compound was determined by employing the powder X-ray diffraction method and was found to crystallize in the monoclinic P21/n space group with the cell constants of a = 5.4716(1) A, b = 5.6165(1) A, c = 7.8168 (1) A, and beta = 89.889 (2) degrees . The temperature-dependent magnetic susceptibility data suggest that this novel S = (3)/2 compound undergoes an antiferromagnetic transition at ~ 69 K. Fitting the high-temperature susceptibility data (100-300 K) to Currie-Weisse behavior showed C = 1.734 emu.K/mol (MUeff = 3.72 bohr magnetons) and theta = 341 K, which is indicative of dominant antiferromagnetic interactions. Temperature-dependent specific heat measurements exhibit a lambda shape anomaly at 69 K, which is consistent with a long-range ordering of the spins. Because of a triangular arrangement of antiferromagnetically ordered magnetic ions, the system exhibits some degree of geometric magnetic frustration (GMF), but not strongly. Spin-dimer analysis, employing extended Huckel theory, reveals that a dominant exchange interaction exists (along the a crystallographic axis in perovskite layer), which violates the perfect condition for GMF. PMID- 26886176 TI - Interfacial Interaction in Anodic Aluminum Oxide Templates Modifies Morphology, Surface Area, and Crystallization of Polyamide-6 Nanofibers. AB - Here, we demonstrated that, when the precipitation process of polyamide-6 (PA6) solution happens in cylindrical channels of an anodized aluminum oxide membrane (AAO), interface interactions between a solid surface, solvent, non-solvent, and PA6 will influence the obtained polymer nanostructures, resulting in complex morphologies, increased surface area, and crystallization changes. With the enhancing interaction of PA6 and the AAO surface, the morphology of PA6 nanostructures changes from solid nanofibers, mesoporous, to bamboo-like, while at the same time, metastable gamma-phase domains increase in these PA6 nanostructures. Brunauer-Emmett-Teller (BET) surface areas of solid, bamboo-like, and mesoporous PA6 nanofibers rise from 16, 20.9, to 25 m(2)/g. This study shows that interfacial interaction in AAO template fabrication can be used in manipulating the morphology and crystallization of one-dimensional polymer nanostructures. It also provides us a simple and novel method to create porous PA6 nanofibers with a large surface area. PMID- 26886177 TI - Preanalytical Investigation of Polyunsaturated Fatty Acids and Eicosanoids in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry. AB - BACKGROUND: Preanalytical variables have a great impact on sample matrices and are a source of laboratory errors. The effect of cryobanking, which is gaining great importance recently, requires systematic investigation. The arachidonic acid metabolism is useful as a quality marker since eicosanoids are easily subjected to in vitro oxidation processes. MATERIALS AND METHODS: Polyunsaturated fatty acids (PUFAs) and related metabolites were analyzed by online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry. The influence of different plasma anticoagulants, as well as serum, freeze-thaw cycles (n = 5), short-term storage at 4 degrees C, room temperature up to 120 minutes, and long-term storage at -20 degrees C, -80 degrees C, and -150 degrees C up to 180 days, were investigated. We further investigated the influence of protein depletion, antioxidants, and shock-freezing on plasma. RESULTS: PUFA metabolites were stable at 4 degrees C in ethylenediaminetetraacetic acid (EDTA) stabilized whole blood for 120 minutes and in EDTA-plasma for 30 minutes. Plasma stability at 4 degrees C could be further increased up to 7 days after protein depletion, while addition of antioxidants such as butylated hydroxytoluene or coverage with nitrogen had no protective effects. Repeated freeze-thaw cycles (n > 1) resulted in eicosanoid formation up to 63%. Long-term storage at -20 degrees C led to substantial eicosanoid increases after 30 days, which could be prevented by depleting proteins before storage. Cryobanking at -80 degrees C and -150 degrees C revealed decreased concentrations of eight eicosanoids after 180 days. An advantage of shock-freezing with liquid nitrogen could not be confirmed compared to conventional freezing. CONCLUSION: Defined preanalytical conditions for eicosanoid analysis in human matrices are required to minimize in vitro data variability. PMID- 26886178 TI - N-Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes. AB - A flow process for N-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate N-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71-99%), productivities (up to 2.6 g h(-1)), and current efficiencies (65-91%) were realized for 19 amides. PMID- 26886179 TI - Empiric antibiotic selection and risk prediction of drug-resistant pathogens in community-onset pneumonia. AB - PURPOSE OF REVEIW: Empiric antibiotic selection in community-onset pneumonia is complicated by uncertainty regarding risk of drug-resistant pathogens (DRPs). The healthcare-associated pneumonia (HCAP) criteria have limited predictive value and lead to unnecessary antibiotic use. Better methods of predicting risk of DRP and selecting empiric antibiotics are needed. Here we give an update on risk factors for DRP, available risk prediction models, and treatment strategy in patients with pneumonia. RECENT FINDINGS: Evidence supporting factors that contribute to risk of DRP has improved since the advent of HCAP. Many of these risk factors have been reproducibly identified in heterogeneous populations. Newer methods of predicting DRP based on these factors demonstrate better performance than HCAP. Recent innovations include the potential to discriminate between risk for methicillin-resistant Staphylococcus aureus and other DRP, and use of severity as a modifier of treatment threshold. However, there is wide variation in included predictor variables, and at proposed thresholds most scores still favor overtreatment. SUMMARY: Until reliable molecular diagnostics are available, additional development and validation of decision support models integrating local resistance rates, estimated DRP risk, severity, and threshold for anti-DRP antibiotics are needed. Once optimized models are identified, implementation studies will be needed to confirm safety and efficacy. PMID- 26886181 TI - Developing a core set of patient-reported outcomes in pancreatic cancer: A Delphi survey. AB - BACKGROUND: Patient-reported outcomes (PROs) are amongst the most relevant outcome measures in pancreatic cancer care and research. However, it is unknown which out of the numerous PROs are most important to patients and health care professionals (HCPs) in this setting. The aim of this study was to identify a core set of PROs to be incorporated in a nationwide prospective multidisciplinary pancreatic cancer registry. PATIENTS AND METHODS: We performed a two-round Delphi survey among 150 patients diagnosed with pancreatic or periampullary cancer (treated either with curative intent or in palliative setting) and 78 HCPs (surgeons, medical oncologists, gastroenterologists, radiotherapists, nurses, and dietitians) in The Netherlands. In round 1, participants were invited to rate the importance of 53 PROs, which were extracted from 17 different PRO measures and grouped into global domains, on a 1-9 Likert scale. PROs rated as very important (score 7-9) by the majority (>= 80%) of curative and/or palliative patients as well as HCPs were considered sufficiently important to be incorporated in the core set. PROs not fulfilling these criteria in round 1 were presented again to the participants in round 2 along with individual and group feedback. RESULTS: A total of 97 patients (94%) in curative-intent setting, 38 patients (81%) in palliative setting and 73 HCPs (94%) completed both rounds 1 and 2. After the first round, 7 PROs were included in the core set: general quality of life, general health, physical ability, satisfaction with caregivers, satisfaction with services and care organisation, coping and defecation. After the second round, 10 additional PROs were added: appetite, ability to work/do usual activities, medication use, weight changes, fatigue, negative feelings, positive feelings, fear of recurrence, relationship with partner/family, and pancreatic enzyme replacement therapy use. CONCLUSION: This study provides a core set of PROs selected by patients and HCPs, which may be incorporated in pancreatic cancer care and research. Validation outside the Dutch context is recommended for generalisation and use in international studies. PMID- 26886182 TI - An ultrafast turn-on thiol probe for protein labeling and bioimaging. AB - A novel turn-on type of ultrafast biothiol fluorescent probe, Naph-EA-mal, was designed, synthesized and evaluated. The probe contains a naphthalimide moiety as a fluorophore, a maleimide unit as a thiol acceptor, and 1,2-ethylenediamine as a linker. Naph-EA-mal displays high selectivity and a fast response toward thiols in aqueous solution. The reaction mechanism of the probe with thiols was confirmed by 1H NMR and HRMS. Test strips were fabricated and a sharp color change was observed by the naked-eye. Furthermore, Naph-EA-mal was successfully applied to label protein thiols, image thiols in living cells, quantify thiol content in cells lysate, and determine the reversible protein thiols oxidation in fixed cells. PMID- 26886180 TI - Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation. AB - RATIONALE: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown. OBJECTIVES: To investigate whether changes in gut microbiota are associated with PCs after HCT. METHODS: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis. MEASUREMENTS AND MAIN RESULTS: One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32 3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and gamma-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas gamma proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49 8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009). CONCLUSIONS: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and gamma-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted. PMID- 26886183 TI - The three branches of Government and financing of the Brazilian Unified National Health System: 2015 in review. PMID- 26886184 TI - [Use and sources of medicines: a population-based study in Campinas, Sao Paulo State, Brazil]. AB - The use of medicines is influenced by different factors. This study aimed to analyze the use of medicines and identify the sources for obtaining them and associated factors, using a population-based cross-sectional design with two stage cluster sampling in Campinas, Sao Paulo State, Brazil, in 2008. Prevalence of use of at least one drug in the 3 previous days was 57.2% and prevalence of obtaining the drug from the Brazilian Unified National Health System (SUS) was 30%. 47.8% of individuals with no health insurance had to pay out-of-pocket for their medication, and 10.9% of individuals with insurance nevertheless obtained their medication from the SUS. Use of medicines obtained from the SUS was associated with older age, widowhood, black or brown skin color, lower schooling and income, and lack of insurance. Only 2.1% reported not being able to obtain the prescribed medication, and the main reasons were lack of availability in the public system and lack of money for out-of-pocket purchases. The study identified the subgroups that obtained most of their medicines in the SUS and showed that these were the subgroups with the lowest use of medicines in the system. PMID- 26886185 TI - Prospective birth cohort in a hyperendemic dengue area in Northeast Brazil: methods and preliminary results. AB - Dengue cases have increased in younger age groups in Brazil. Maternal anti-dengue antibodies can have a protective effect in the first months of life, but their decline can increase the risk of severe dengue. A prospective birth cohort was established in 2011-2012 in the city of Recife, Pernambuco State, Brazil, to determine the incidence of serotype-specific dengue infection and the kinetics of transferred maternal anti-dengue antibodies in the first years of life. This article describes the design, methods and preliminary results of this cohort study. 354 children underwent clinical and laboratory monitoring for two years, with 15% losses to follow-up. The overall rate of new infections was approximately 10% in the first year of follow-up. Information on the force of serotype-specific dengue infection and the evaluation of transferred maternal antibodies can contribute to understanding dengue etiopathogenesis. PMID- 26886186 TI - Does the knowledge of emergency contraception affect its use among high school adolescents? AB - This study aimed to test how knowledge on emergency contraception (according to age at sexual initiation, type of school, and knowing someone that has already used emergency contraception) influences the method's use. This was a cross sectional study in a probabilistic sample of students 15-19 years of age enrolled in public and private middle schools in a medium-sized city in Southeast Brazil (n = 307). Data were collected in 2011 using a self-administered questionnaire. A structural equations model was used for the data analysis. Considering age at sexual initiation and type of school, knowledge of emergency contraception was not associated with its use, but knowing someone that had used the method showed a significant mean effect on use of emergency contraception. Peer group conversations on emergency contraception appear to have greater influence on use of the method than knowledge itself, economic status, or sexual experience. PMID- 26886187 TI - [Frequency of self-reported vocal problems and associated occupational factors in primary schoolteachers in Londrina, Parana State, Brazil]. AB - This study aimed to estimate the prevalence of self-reported vocal problems among primary schoolteachers and to identify associated occupational factors, using a cross-sectional design and face-to-face interviews with 967 teachers in 20 public schools in Londrina, Parana State, Brazil. Prevalence of self-reported vocal problems was 25.7%. Adjusted analyses showed associations with characteristics of the employment relationship (workweek >= 40 hours and poor perception of salaries and health benefits), characteristics of the work environment (number of students per class and exposure to chalk dust and microorganisms), psychological factors (low job satisfaction, limited opportunities to express opinions, worse relationship with superiors, and poor balance between professional and personal life), and violence (insults and bullying). Vocal disorders affected one in four primary schoolteachers and were associated with various characteristics of the teaching profession (both structural and work-related). PMID- 26886188 TI - Protonic Ammonium Nitrate Ionic Liquids and Their Mixtures: Insights into Their Thermophysical Behavior. AB - This study is centered on the thermophysical characterization of different families of alkylammonium nitrate ionic liquids and their binary mixtures, namely the determination at atmospheric pressure of densities, electric conductivities and viscosities in the 288.15 < T/K < 353.15 range. First, measurements focusing on ethylammonium, propylammonium and butylammonium nitrate systems, and their binary mixtures, were determined. These were followed by studies involving binary mixtures composed of ethylammonium nitrate (with three hydrogen bond donor groups) and different homologous ionic liquids with differing numbers of hydrogen bond donor groups: diethylammonium nitrate (two hydrogen bond donors), triethylammonium nitrate (one hydrogen bond donor) and tetraethylammonium nitrate (no hydrogen bond donors). Finally, the behavior of mixtures with different numbers of equivalent carbon atoms in the alkylammonium cations was analyzed. The results show a quasi-ideal behavior for all monoalkylammonium nitrate mixtures. In contrast, the other mixtures show deviations from ideality, namely when the difference in the number of carbon atoms present in the cations increases or the number of hydrogen bond donors present in the cation decreases. Overall, the results clearly show that, besides the length and distribution of alkyl chains present in a cation such as alkylammonium, there are other structural and interaction parameters that influence the thermophysical properties of both pure compounds and their mixtures. PMID- 26886189 TI - Cognitive Impairment in Transient Ischemic Attack Patients: A Systematic Review. AB - BACKGROUND: Although by definition a transient ischemic attack (TIA) lasts less than 24 h, many patients experience cognitive complaints beyond focal symptom resolution. However, their prevalence, causes and profile are unclear. We therefore performed a systematic review on cognitive impairment after TIA. SUMMARY: Medline and Embase were searched for relevant studies. Risk of bias was assessed, and data synthesis was performed according to the severity of cognitive impairment. Thirteen studies were included, with considerable heterogeneity concerning methods and timing of cognitive testing. Confounding, detection bias and attrition were the main causes of a high risk of bias in several studies. The prevalence of post-TIA mild cognitive impairment ranged from 29 to 68%. Severe cognitive impairment was found in 8-22% of patients. Studies using a cognitive screening instrument and those performed shortly after TIA or several years later, reported the highest frequencies of impairment. Patients evaluated with a screening tool were substantially older than those who underwent a full neuropsychological assessment (weighted mean age difference 10.9 years). Based on limited data, the post-TIA cognitive profile showed prominent executive function deficits. Insufficient data refrained us from drawing conclusions on causality. The few studies that reported neuroimaging results found a minor correlation with cognitive impairment. KEY MESSAGES: Mild cognitive impairment is present in more than a third of the TIA patients and has a profile comparable with vascular cognitive impairment. Reported rates of post-TIA cognitive impairment are highly variable and higher frequencies are found with cognitive screening tools. Considerable heterogeneity and insufficient data limit further conclusions about potential causative factors. PMID- 26886190 TI - Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression. AB - Enhanced renin-angiotensin activity causes hypertension and cardiac hypertrophy. The angiotensin (Ang)-converting enzyme (ACE)2/Ang(1-7)/Mas axis pathway functions against Ang II type 1 receptor (AT1R) signaling. We investigated whether olmesartan (Olm), an AT1R blocker, inhibits cardiac hypertrophy independently of blood pressure, and evaluated the potential mechanisms. The 3- to 4-month-old male mice overexpressing renin in the liver (Ren-Tg) were given Olm (5 mg/kg/d) and hydralazine (Hyd) (3.5 mg/kg/d) orally for 2 months. Systolic blood pressure was higher in the Ren-Tg mice than in wild-type littermates. Olm and Hyd treatments lowered systolic blood pressure to the same degree. However, cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression, was inhibited by only Olm treatment, but not by Hyd. Olm treatment reversed decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibited enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species, whereas Hyd treatment had no influence on them. These findings indicate that Olm treatment inhibits cardiac hypertrophy independently of blood pressure, not only through its original AT1R blockade but partly through enhancement of ACE2/Ang(1-7)/Mas axis and suppression of Nox4 expression. PMID- 26886191 TI - Pushing the Envelope on the Indications and Doses of Pulmonary Arterial Hypertension Medications: What Is Reasonable? PMID- 26886192 TI - Metabolic engineering of Klebsiella pneumoniae and in silico investigation for enhanced 2,3-butanediol production. AB - OBJECTIVES: To improve the production of 2,3-butanediol (2,3-BD) in Klebsiella pneumoniae, the genes related to the formation of lactic acid, ethanol, and acetic acid were eliminated. RESULTS: Although the cell growth and 2,3-BD production rates of the K. pneumoniae DeltaldhA DeltaadhE Deltapta-ackA strain were lower than those of the wild-type strain, the mutant produced a higher titer of 2,3-BD and a higher yield in batch fermentation: 91 g 2,3-BD/l with a yield of 0.45 g per g glucose and a productivity of 1.62 g/l.h in fed-batch fermentation. The metabolic characteristics of the mutants were consistent with the results of in silico simulation. CONCLUSIONS: K. pneumoniae knockout mutants developed with an aid of in silico investigation could produce higher amounts of 2,3-BD with increased titer, yield, and productivity. PMID- 26886193 TI - RETRACTED ARTICLE: Extract from the brown seaweed Ascophyllum nodosum as an elicitor of resistance to Fusarium oxysporum f. sp. radicis-lycopersici in tomato. PMID- 26886194 TI - A New Fishfly Species (Megaloptera: Corydalidae: Neohermes Banks) Discovered from North America by a Systematic Revision, with Phylogenetic and Biogeographic Implications. AB - The taxonomy of Megaloptera from the Nearctic region is fairly well known and their faunal diversity has been largely surveyed, even in relatively remote regions. However, the evolutionary history of Nearctic Megaloptera is still poorly known with phylogenetic and biogeographic studies lacking. In this paper, we report a new fishfly species of the endemic North American genus Neohermes Banks, 1908, increasing the total number known of species to six. This new species (Neohermes inexpectatus sp. nov.) is currently known to occur only in California (USA) and is apparently confined to the Northern Coastal Range. The new species resembles the three Neohermes species from eastern North America based on the relatively small body size and the presence of female gonostyli 9. However, our phylogenetic analysis using adult morphological data recovered the new species as the sister species to the remaining Neohermes, which includes two species from western North America and three from eastern North America. According to the present interspecific phylogeny of Neohermes, with reconstructed ancestral areas, the initial divergence within the genus was found to take place in western North America, with a subsequent eastward dispersal. This likely lead to the modern distribution of Neohermes in eastern North America with the closure of the Mid-Continental Seaway, which separated western and eastern North America in the Mid-Late Cretaceous (100-80 MYA) and finally disappeared at the end of the Cretaceous (70 MYA). The uplift of the Cordilleran System probably accounted for the divergence between the eastern and two western Neohermes species. PMID- 26886196 TI - Inducible Defenses with a "Twist": Daphnia barbata Abandons Bilateral Symmetry in Response to an Ancient Predator. AB - Predation is one of the most important drivers of natural selection. In consequence a huge variety of anti-predator defenses have evolved in prey species. Under unpredictable and temporally variable predation pressure, the evolution of phenotypically plastic defensive traits is favored. These "inducible defenses", range from changes in behavior, life history, physiology to morphology and can be found in almost all taxa from bacteria to vertebrates. An important group of model organisms in ecological, evolutionary and environmental research, water fleas of the genus Daphnia (Crustacea: Cladocera), are well known for their ability to respond to predators with an enormous variety of inducible morphological defenses. Here we report on the "twist", a body torsion, as a so far unrecognized inducible morphological defense in Daphnia, expressed by Daphnia barbata exposed to the predatory tadpole shrimp Triops cancriformis. This defense is realized by a twisted carapace with the helmet and the tail spine deviating from the body axis into opposing directions, resulting in a complete abolishment of bilateral symmetry. The twisted morphotype should considerably interfere with the feeding apparatus of the predator, contributing to the effectiveness of the array of defensive traits in D. barbata. As such this study does not only describe a completely novel inducible defense in the genus Daphnia but also presents the first report of a free living Bilateria to flexibly respond to predation risk by abandoning bilateral symmetry. PMID- 26886195 TI - Involvement of a Novel Class C Beta-Lactamase in the Transglutaminase Mediated Cross-Linking Cascade of Streptomyces mobaraensis DSM 40847. AB - Streptomyces mobaraensis DSM 40847 secretes transglutaminase that cross-links proteins via gamma-glutamyl-epsilon-lysine isopeptide bonds. Characterized substrates are inhibitory proteins acting against various serine, cysteine and metalloproteases. In the present study, the bacterial secretome was examined to uncover additional transglutaminase substrates. Fractional ethanol precipitation of the exported proteins at various times of culture growth, electrophoresis of the precipitated proteins, and sequencing of a 39 kDa protein by mass spectrometry revealed the novel beta-lactamase Sml-1. As indicated by biotinylated probes, Sml-1, produced in E. coli, exhibits glutamine and lysine residues accessible for transglutaminase. The chromogenic cephalosporin analogue, nitrocefin, was hydrolyzed by Sml-1 with low velocity. The obtained Km and kcat values of the recombinant enzyme were 94.3+/-1.8 MUM and 0.39+/-0.03 s(-1), respectively. Penicillin G and ampicillin proved to be weak inhibitors of nitrocefin hydrolysis (Ki of 0.1 mM and 0.18 mM). Negligible influence of metals on beta-lactamase activity ruled out that Sml-1 is a Zn2+-dependent class B beta lactamase. Rather, sequence motifs such as SITK, YSN, and HDG forming the active core in a hypothetical structure may be typical for class C beta-lactamases. Based on the results, we assume that the novel transglutaminase substrate ensures undisturbed growth of aerial hyphae in Streptomyces mobaraensis by trapping and inactivating hostile beta-lactam antibiotics. PMID- 26886197 TI - Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India. AB - Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species. PMID- 26886200 TI - Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy. AB - Limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous and the diagnostic work-up including conventional genetic testing using Sanger sequencing remains complex and often unsatisfactory. We performed targeted sequencing of 23 LGMD-related genes and 15 genes in which alterations result in a similar phenotype in 58 patients with genetically unclassified LGMDs. A genetic diagnosis was possible in 19 of 58 patients (33 %). LGMD2A was the most common form, followed by LGMD2L and LGMD2I. In two patients, pathogenic mutations were identified in genes that are not classified as LGMD genes (glycogen branching enzyme and valosin-containing protein). Thus, a focused next-generation sequencing-based gene panel is a rather satisfactory tool for the diagnosis in unclassified LGMDs. PMID- 26886198 TI - ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity. AB - AIMS/HYPOTHESIS: Dissipating energy via mitochondrial uncoupling has been suggested to contribute to enhanced insulin sensitivity. We hypothesised that skeletal muscle mitochondria of endurance-trained athletes have increased sensitivity for fatty acid (FA)-induced uncoupling, which is driven by the mitochondrial protein adenine nucleotide translocase 1 (ANT1). METHODS: Capacity for FA-induced uncoupling was measured in endurance-trained male athletes (T) and sedentary young men (UT) in an observational study and also in isolated skeletal muscle mitochondria from Zucker diabetic fatty (ZDF) rats and C2C12 myotubes following small interfering RNA (siRNA)-mediated gene silencing of ANT1. Thus, fuelled by glutamate/succinate (fibres) or pyruvate (mitochondria and myotubes) and in the presence of oligomycin to block ATP synthesis, increasing levels of oleate (fibres) or palmitate (mitochondria and myotubes) were automatically titrated while respiration was monitored. Insulin sensitivity was measured by hyperinsulinaemic-euglycaemic clamp in humans and via insulin-stimulated glucose uptake in myotubes. RESULTS: Skeletal muscle from the T group displayed increased sensitivity to FA-induced uncoupling (p = 0.011) compared with muscle from the UT group, and this was associated with elevated insulin sensitivity (p = 0.034). ANT1 expression was increased in T (p = 0.013). Mitochondria from ZDF rats displayed decreased sensitivity for FA-induced uncoupling (p = 0.008). This difference disappeared in the presence of the adenine nucleotide translocator inhibitor carboxyatractyloside. Partial knockdown of ANT1 in C2C12 myotubes decreased sensitivity to the FA-induced uncoupling (p = 0.008) and insulin stimulated glucose uptake (p = 0.025) compared with controls. CONCLUSIONS/INTERPRETATION: Increased sensitivity to FA-induced uncoupling is associated with enhanced insulin sensitivity and is affected by ANT1 activity in skeletal muscle. FA-induced mitochondrial uncoupling may help to preserve insulin sensitivity in the face of a high supply of FAs. TRIAL REGISTRATION: www.trialregister.nl NTR2002. PMID- 26886201 TI - Prevalence of multiple sclerosis in the Lazio region, Italy: use of an algorithm based on health information systems. AB - Compared with other areas of the country, very limited data are available on multiple sclerosis (MS) prevalence in Central Italy. We aimed to estimate MS prevalence in the Lazio region and its geographical distribution using regional health information systems (HIS). To identify MS cases we used data from drug prescription, hospital discharge and ticket exemption registries. Crude, age- and gender-specific prevalence estimates on December 31, 2011 were calculated. To compare MS prevalence between different areas within the region, we calculated age- and gender-adjusted prevalence and prevalence ratios using a multivariate Poisson regression model. Crude prevalence rate was 130.5/100,000 (95 % CI 127.5 133.5): 89.7/100,000 for males and 167.9/100,000 for females. The overall prevalence rate standardized to the European Standard Population was 119.6/100,000 (95 % CI 116.8-122.4). We observed significant differences in MS prevalence within the region, with estimates ranging from 96.3 (95 % CI 86.4 107.3) for Latina to 169.6 (95 % CI 147.6-194.9) for Rieti. Most districts close to the coast showed lower prevalence estimates compared to those situated in the eastern mountainous area of the region. In conclusion, this study produced a MS prevalence estimate at regional level using population-based health administrative databases. Our results showed the Lazio region is a high-risk area for MS, although with an uneven geographical distribution. While some limitations must be considered including possible prevalence underestimation, HIS represent a valuable source of information to measure the burden of SM, useful for epidemiological surveillance and healthcare planning. PMID- 26886202 TI - Impaired renal function is related to deep and mixed, but not strictly lobar cerebral microbleeds in patients with ischaemic stroke and TIA. AB - The vasculature of the brain and kidneys are similarly vulnerable to hypertension, so their microvascular damage may be correlated. We investigated the relationship of renal function to the anatomical distribution of cerebral microbleeds (CMBs), a marker of underlying cerebral small vessel disease (hypertensive arteriopathy or cerebral amyloid angiopathy), in a Western patient cohort. This was a retrospective study of referrals to a hospital stroke service. All patients with clinical data and a T2*-weighted gradient-recalled echo (T2* GRE) MRI were included. MRI scans were rated for CMBs using the Microbleed Anatomical Rating Scale. Renal function was assessed by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. We included 202 patients, 39 with CMBs (19.3 %); 15 had "strictly lobar", 12 had "strictly deep" and 12 had "mixed" CMBs. Patients without CMBs had a higher eGFR than those with CMBs (mean difference 6.50 ml/min/1.73 m(2), 95 % CI -14.73 to 1.72 ml/min/1.73 m(2), p = 0.121). Multivariable analysis found that those with deep and mixed CMBs had a lower eGFR than those without CMBs (mean difference 10.70 ml/min/1.73 m(2), 95 % CI -20.35 to -1.06 ml/min/1.73 m(2), p = 0.030). There was no difference in eGFR found between those with strictly lobar CMBs and those without CMBs (mean difference -1.59 ml/min/1.73 m(2), 95 % CI -13.08 to 9.89 ml/min/1.73 m(2), p = 0.79). In a Western patient cohort, there appears to be an association between eGFR and the presence of deep and mixed CMBs, but not strictly lobar CMBs. This suggests a shared vulnerability of renal afferent and cerebral deep and superficial perforating arterioles to systemic hypertension. The arteriopathy underlying strictly lobar CMBs (i.e. cerebral amyloid angiopathy), appears to be less related to renal impairment. PMID- 26886203 TI - Two cases of multiple sclerosis manifesting after in vitro fertilization procedures. PMID- 26886205 TI - Cognitive and neuropsychological evolution in children with anti-NMDAR encephalitis. AB - We describe neurological and cognitive/neuropsychological changes from symptom onset in 13 consecutive children (8 females and 5 males; median age 11 years, range 3-17) with anti-NMDAR-encephalitis. We assessed neurological status using the modified Rankin Scale for children and cognitive/neuropsychological status using a standardized battery that was administered serially in 10 prospective patients, and at latest follow-up in three retrospective patients diagnosed before study initiation. Symptom onset was marked by neurological or psychiatric/behavioural manifestations, which became severe but regressed at variable rates after starting immunotherapy. The 10 prospective patients were able to undergo first standardized cognitive/neuropsychological assessment a median of 3 months (range 1-12) after symptom onset: they had extensive deficits, although severity varied. Subsequent assessment showed marked improvements although the timescale varied. At latest evaluation (median 31 months, range 3 112, after symptom onset), seven patients had no neurological disability, five had improved substantially, and one had persistent behavioural problems. Latest cognitive/neuropsychological assessment in 11 patients with at least a year of follow-up showed normal general intellectual abilities, but over half had residual deficits indicating frontal lobe dysfunction. All patients had resumed normal activities. Our findings suggest that early installation of immunotherapy results in good long-term recovery in most paediatric patients with anti-NMDAR encephalitis, however, recovery is incomplete and the disease leaves subtle lasting defects that impact quality of life, social relationships, and academic achievement. PMID- 26886204 TI - Spring cleaning: time to rethink imaging research lines in MS? AB - Together with recently advanced MRI technological capability, new needs and updated questions are emerging in imaging research in multiple sclerosis (MS), especially with respect to the identification of novel in vivo biomarkers of MS relevant pathological processes. Expected benefits will involve approaches to diagnosis and clinical classification. In detail, three main points of discussion are addressed in this review: (1) new imaging biomarkers (centrifugal/centripetal lesion enhancement, central vein, paramagnetic rims at the lesion edge, subpial cortical demyelination); (2) thinking about high-resolution MR from a pathological perspective (from postmortem to in vivo staging); and (3) the clinical utility of quantitative MRI. In this context, research efforts should increasingly be focused on the direct in vivo visualization of "hidden" inflammation, beyond what can be detected with conventional gadolinium-based methods, as well as remyelination and repair, since these are likely to represent critical pathological processes and potential therapeutic targets. Concluding remarks concern the limitations, challenges, and ultimately clinical role of non conventional MRI techniques. PMID- 26886207 TI - Does the Establishment of Sustainable Use Reserves Affect Fire Management in the Humid Tropics? AB - Tropical forests are experiencing a growing fire problem driven by climatic change, agricultural expansion and forest degradation. Protected areas are an important feature of forest protection strategies, and sustainable use reserves (SURs) may be reducing fire prevalence since they promote sustainable livelihoods and resource management. However, the use of fire in swidden agriculture, and other forms of land management, may be undermining the effectiveness of SURs in meeting their conservation and sustainable development goals. We analyse MODIS derived hot pixels, TRMM rainfall data, Terra-Class land cover data, socio ecological data from the Brazilian agro-census and the spatial extent of rivers and roads to evaluate whether the designation of SURs reduces fire occurrence in the Brazilian Amazon. Specifically, we ask (1) a. Is SUR location (i.e., de facto) or (1) b. designation (i.e. de jure) the driving factor affecting performance in terms of the spatial density of fires?, and (2), Does SUR creation affect fire management (i.e., the timing of fires in relation to previous rainfall)? We demonstrate that pre-protection baselines are crucial for understanding reserve performance. We show that reserve creation had no discernible impact on fire density, and that fires were less prevalent in SURs due to their characteristics of sparser human settlement and remoteness, rather than their status de jure. In addition, the timing of fires in relation to rainfall, indicative of local fire management and adherence to environmental law, did not improve following SUR creation. These results challenge the notion that SURs promote environmentally sensitive fire-management, and suggest that SURs in Amazonia will require special attention if they are to curtail future accidental wildfires, particularly as plans to expand the road infrastructure throughout the region are realised. Greater investment to support improved fire management by farmers living in reserves, in addition to other fire users, will be necessary to help ameliorate these threats. PMID- 26886208 TI - Of rodents and men: understanding the emergence of motor and cognitive symptoms in Huntington disease. AB - Arguably, one of the most important milestones in Huntington disease research since the discovery of the gene responsible has been the generation of different genetic animal models. Although clinical reports have shown evidence of progressive cognitive impairments in gene carriers before motor symptoms are diagnosed, such symptoms have been much less obvious in animal models. In this review, we summarize the three main classes of animal models for Huntington disease and describe some relevant translational assays for behavioural deficits evaluation. Finally, we argue that a good knowledge of the emergence of motor and cognitive symptoms in mice and rat models is indispensable for the selection of endpoint measures in early preclinical drug screening studies. PMID- 26886210 TI - Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers. AB - The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e cigarettes among e-cigarette naive smokers. PMID- 26886206 TI - Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society. AB - Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder of neuromuscular synaptic transmission. The clinical hallmark of MG consists of fluctuating fatigability and weakness affecting ocular, bulbar and (proximal) limb skeletal muscle groups. MG may either occur as an autoimmune disease with distinct immunogenetic characteristics or as a paraneoplastic syndrome associated with tumors of the thymus. Impairment of central thymic and peripheral self tolerance mechanisms in both cases is thought to favor an autoimmune CD4(+) T cell-mediated B cell activation and synthesis of pathogenic high-affinity autoantibodies of either the IgG1 and 3 or IgG4 subclass. These autoantibodies bind to the nicotinic acetylcholine receptor (AchR) itself, or muscle-specific tyrosine-kinase (MuSK), lipoprotein receptor-related protein 4 (LRP4) and agrin involved in clustering of AchRs within the postsynaptic membrane and structural maintenance of the neuromuscular synapse. This results in disturbance of neuromuscular transmission and thus clinical manifestation of the disease. Emphasizing evidence from clinical trials, we provide an updated overview on immunopathogenesis, and derived current and future treatment strategies for MG divided into: (a) symptomatic treatments facilitating neuromuscular transmission, (b) antibody-depleting treatments, and PMID- 26886209 TI - Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys. AB - The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID- 26886211 TI - Trastuzumab-associated autoimmune thyroid disease in a patient with metastatic breast cancer. PMID- 26886212 TI - Comparative study on the epidemiological aspects of enterohemorrhagic Escherichia coli infections between Korea and Japan, 2006 to 2010. AB - BACKGROUND/AIMS: To compare the epidemiological aspects of enterohemorrhagic Escherichia coli (EHEC) between Korea and Japan by analyzing the current state of EHEC infection outbreaks and related risk factors. METHODS: We investigated the epidemiological aspects of EHEC infection cases between Korea and Japan from 2006 to 2010. The following factors were analyzed: national prevalence rate (PR), regional prevalence rate, epidemic aspects (i.e., Cases related to gender), male to female morbidity ratio, age, and seasonal distribution. RESULTS: In total, there were 254 cases of EHEC with an average PR of 0.11 per 100,000 populations in Korea from 2006 to 2010. During the same period in Japan, there were 20,883 cases of EHEC with an average PR of 3.26 per 100,000 populations. The PR in Japan was significantly higher than that in Korea (p < 0.01). In both countries, more females than males had EHEC infections, with the highest incidence of infections (> 50%) observed for individuals younger than 9 years. EHEC is an emerging zoonosis and may be caused by consumption of raw or undercooked meat products from ruminants. CONCLUSIONS: This study provides a quantitative analysis of the epidemiological aspects and risk factors of EHEC infections in Korea and Japan and will provide insight on effective future strategies to reduce these infections. PMID- 26886213 TI - Hepatocellular carcinoma hidden by multiple infarcted regenerative nodules. PMID- 26886214 TI - Engineering TaqII bifunctional endonuclease DNA recognition fidelity: the effect of a single amino acid substitution within the methyltransferase catalytic site. AB - The aim of this study was to improve a useful molecular tool-TaqII restriction endonuclease-methyltransferase-by rational protein engineering, as well as to show an application of our novel method of restriction endonuclease activity modulation through a single amino acid change in the NPPY motif of methyltransferase. An amino acid change was introduced using site-directed mutagenesis into the taqIIRM gene. The mutated gene was expressed in Escherichia coli. The protein variant was purified and characterized. Previously, we described a TspGWI variant with an amino acid change in the methyltransferase motif IV. Here, we investigate a complex, pleiotropic effect of an analogous amino acid change on its homologue-TaqII. The methyltransferase activity is reduced, but not abolished, while TaqII restriction endonuclease can be reactivated by sinefungin, with an increased DNA recognition fidelity. The general method for engineering of the IIS/IIC/IIG restriction endonuclease activity/fidelity is developed along with the generation of an improved TaqII enzyme for biotechnological applications. A successful application of our novel strategy for restriction endonuclease activity/fidelity alteration, based on bioinformatics analyses, mutagenesis and the use of cofactor-analogue activity modulation, is presented. PMID- 26886215 TI - Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics. AB - Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to minimize undesired side effects due to systemic distribution in the organism. Using magnetic drug particles under the influence of an external magnetic field, the drug particles are navigated toward the target region. Herein, computational fluid dynamics was used to simulate the air flow and magnetic particle deposition in a realistic human airway geometry obtained by CT scan images. Using discrete phase modeling and one-way coupling of particle-fluid phases, a Lagrangian approach for particle tracking in the presence of an external non-uniform magnetic field was applied. Polystyrene (PMS40) particles were utilized as the magnetic drug carrier. A parametric study was conducted, and the influence of particle diameter, magnetic source position, magnetic field strength and inhalation condition on the particle transport pattern and deposition efficiency (DE) was reported. Overall, the results show considerable promise of MDT in deposition enhancement at the target region (i.e., left lung). However, the positive effect of increasing particle size on DE enhancement was evident at smaller magnetic field strengths (Mn [Formula: see text] 1.5 T), whereas, at higher applied magnetic field strengths, increasing particle size has a inverse effect on DE. This implies that for efficient MTD in the human respiratory system, an optimal combination of magnetic drug career characteristics and magnetic field strength has to be achieved. PMID- 26886216 TI - Fat King Penguins Are Less Steady on Their Feet. AB - Returning to the shore after a feeding sojourn at sea, king penguins often undertake a relatively long terrestrial journey to the breeding colony carrying a heavy, mostly frontal, accumulation of fat along with food in the stomach for chick-provisioning. There they must survive a fasting period of up to a month in duration, during which their complete reliance on endogenous energy stores results in a dramatic loss in body mass. Our aim was to determine if the king penguin's walking gait changes with variations in body mass. We investigated this by walking king penguins on a treadmill while instrumented with an acceleration data logger. The stride frequency, dynamic body acceleration (DBA) and posture of fat (pre-fasting; 13.2 kg) and slim (post fasting; 11 kg) king penguins were assessed while they walked at the same speed (1.4 km/h) on a treadmill. Paired statistical tests indicated no evidence for a difference in dynamic body acceleration or stride frequency between the two body masses however there was substantially less variability in both leaning angle and the leaning amplitude of the body when the birds were slimmer. Furthermore, there was some evidence that the slimmer birds exhibited a decrease in waddling amplitude. We suggest the increase in variability of both leaning angle and amplitude, as well as a possibly greater variability in the waddling amplitude, is likely to result from the frontal fat accumulation when the birds are heavier, which may move the centre of mass anteriorly, resulting in a less stable upright posture. This study is the first to use accelerometry to better understand the gait of a species within a specific ecological context: the considerable body mass change exhibited by king penguins. PMID- 26886217 TI - The degradation of two fluoroquinolone based antimicrobials by SilA, an alkaline laccase from Streptomyces ipomoeae. AB - The presence of fluoroquinolone based antimicrobials in natural waters represents a significant emerging environmental problem. In this study the suitability of a novel alkaline bacterial laccase, SilA, from Streptomyces ipomoeae to degrade two key antimicrobials, Ciprofloxacin and Norfloxacin under alkaline conditions in the presence of natural mediators was assessed. Results showed that only the selected SilA-acetosyringone system was able to degrade more than 90% of both fluoroquinolones. HPLC analysis of the degradation products obtained after enzyme treatment confirmed the disappearance of the antimicrobials and the mediator after 24 h. The time course of the degradation showed that during the first 4 h a 75% of degradation of fluoroquinolones was detected while the mediator remained stable. A concomitant appearance of new chromatographic peaks derived from the fluoroquinolones and/or the mediator was detected. Moreover, toxicity assays demonstrated that the SilA-acetosyringone system was able to reduce the toxicity of Ciprofloxacin and Norfloxacin by 90 and 70%, respectively. In conclusion, these findings support the suitability of a low cost and environmentally friendly strategy based on the SilA-acetosyringone system for a primary treatment of contaminated alkaline wastewaters with this type of emerging pollutants. PMID- 26886218 TI - The Effects of Classroom Interventions on Off-Task and Disruptive Classroom Behavior in Children with Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analytic Review. AB - Children with attention-deficit/hyperactivity disorder (ADHD) often exhibit problem behavior in class, which teachers often struggle to manage due to a lack of knowledge and skills to use classroom management strategies. The aim of this meta-analytic review was to determine the effectiveness of several types of classroom interventions (antecedent-based, consequence-based, self-regulation, combined) that can be applied by teachers in order to decrease off-task and disruptive classroom behavior in children with symptoms of ADHD. A second aim was to identify potential moderators (classroom setting, type of measure, students' age, gender, intelligence, and medication use). Finally, it was qualitatively explored whether the identified classroom interventions also directly or indirectly affected behavioral and academic outcomes of classmates. Separate meta analyses were performed on standardized mean differences (SMDs) for 24 within subjects design (WSD) and 76 single-subject design (SSD) studies. Results showed that classroom interventions reduce off-task and disruptive classroom behavior in children with symptoms of ADHD (WSDs: MSMD = 0.92; SSDs: MSMD = 3.08), with largest effects for consequence-based (WSDs: MSMD = 1.82) and self-regulation interventions (SSDs: MSMD = 3.61). Larger effects were obtained in general education classrooms than in other classroom settings. No reliable conclusions could be formulated about moderating effects of type of measure and students' age, gender, intelligence, and medication use, mainly because of power problems. Finally, classroom interventions appeared to also benefit classmates' behavioral and academic outcomes. PMID- 26886219 TI - Rural to Urban Population Density Scaling of Crime and Property Transactions in English and Welsh Parliamentary Constituencies. AB - Urban population scaling of resource use, creativity metrics, and human behaviors has been widely studied. These studies have not looked in detail at the full range of human environments which represent a continuum from the most rural to heavily urban. We examined monthly police crime reports and property transaction values across all 573 Parliamentary Constituencies in England and Wales, finding that scaling models based on population density provided a far superior framework to traditional population scaling. We found four types of scaling: i) non-urban scaling in which a single power law explained the relationship between the metrics and population density from the most rural to heavily urban environments, ii) accelerated scaling in which high population density was associated with an increase in the power-law exponent, iii) inhibited scaling where the urban environment resulted in a reduction in the power-law exponent but remained positive, and iv) collapsed scaling where transition to the high density environment resulted in a negative scaling exponent. Urban scaling transitions, when observed, took place universally between 10 and 70 people per hectare. This study significantly refines our understanding of urban scaling, making clear that some of what has been previously ascribed to urban environments may simply be the high density portion of non-urban scaling. It also makes clear that some metrics undergo specific transitions in urban environments and these transitions can include negative scaling exponents indicative of collapse. This study gives promise of far more sophisticated scale adjusted metrics and indicates that studies of urban scaling represent a high density subsection of overall scaling relationships which continue into rural environments. PMID- 26886221 TI - Pigeons perform poorly on a midsession reversal task without rigid temporal regularity. AB - Animals make surprising anticipatory and perseverative errors when faced with a midsession reversal of reinforcer contingencies on a choice task with highly predictable stimulus-time relationships. In the current study, we asked whether pigeons would anticipate changes in reinforcement when the reinforcer contingencies for each stimulus were not fixed in time. We compared the responses of pigeons on a simultaneous choice task when the initially correct stimulus was randomized or alternated across sessions. Pigeons showed more errors overall compared with the typical results of a standard midsession reversal procedure, and they did not show the typical anticipatory errors prior to the contingency reversal. Probe tests that manipulated the spacing between trials also suggested that timing of the session exerted little control of pigeons' behavior. The temporal structure of the experimental session thus appears to be an important determinant for animals' use of time in midsession reversal procedures. PMID- 26886220 TI - Pro-gastrin-releasing peptide and neuron-specific enolase: useful predictors of response to chemotherapy and survival in patients with small cell lung cancer. AB - PURPOSE: The aim of this study was (1) to evaluate and predict the value of ProGRP and NSE in therapy and survival; (2) as well as to investigate the correlation between the ProGRP mRNA expression in peripheral blood and serum ProGRP protein. METHODS: The study included 122 patients with SCLC without prior therapy. The serum levels of ProGRP and NSE were detected by enzyme-linked immunosorbent assay and eletro-chemiluminescence immunoassay, respectively. The expression of ProGRP mRNA was detected by real-time reverse transcriptase polymerase chain reaction. RESULTS: Distribution of serum levels of ProGRP, NSE and ProGRP mRNA differed significantly according to tumor size, disease stage and distant metastasis (all P < 0.05), and no association was found between them and gender or age (both P > 0.05). After two courses of chemotherapy, patients of remission and stable groups showed a marked decrease in ProGRP and NSE concentrations (P < 0.05). The ProGRP concentration of patients in progression group was significantly higher than pretreatment level (P < 0.05), while NSE concentration was not. A linear nonparametric (Spearman) correlation test revealed that there was a significant correlation between ProGRP mRNA expression in peripheral blood and serum ProGRP protein level (P < 0.05). Univariate analysis found a statistically significant association of survival with disease stage, distant metastasis, ProGRP and NSE (P < 0.05). Gender, age and tumor size were not prognostic factors (P > 0.05). Multiple Cox regression model analysis found that only disease stage and NSE were significant predictors (P < 0.05). CONCLUSIONS: This study has found that there is a potential role for ProGRP and NSE in both therapy monitoring and predicting survival in SCLC patients. PMID- 26886222 TI - A Case Series Characterizing Pilomyxoid Astrocytomas in Childhood. AB - BACKGROUND: The term pilomyxoid astrocytoma (PMA) was added to the World Health Organization Classification of Tumours of the central nervous system in 2007. Pilomyxoid tumors are grade II tumors, considered to be variants of pilocytic astrocytomas. We attempted to determine if positron emission tomography (PET), proliferative index (PI), and BRAF V600E mutation help better define PMAs. OBSERVATIONS: We report 5 patients' clinical and neuroimaging findings, pathology (PI), and outcome. Four of the 5 patients had PET scans. Three patients showed [18F]fluoro-deoxyglucose hypermetabolism. The PI was elevated in all 5 cases and the BRAF V600E mutation was found in 3 of the 3 patients tested. CONCLUSION: Our data suggest that PMAs are hypermetabolic on PET, have elevated PIs and BRAF V600E mutations, and behave aggressively. PMID- 26886223 TI - Enhancement in xylose utilization using Kluyveromyces marxianus NIRE-K1 through evolutionary adaptation approach. AB - The evolutionary adaptation was carried out on the thermotolerant yeast Kluyveromyces marxianus NIRE-K1 at 45 degrees C up to 60 batches to enhance its xylose utilization capability. The adapted strain showed higher specific growth rate and 3-fold xylose uptake rate and short lag phase as compared to the native strain. During aerobic growth adapted yeast showed 2.81-fold higher xylose utilization than that of native. In anaerobic batch fermentation, adapted yeast utilized about 91% of xylose in 72 h and produced 2.88 and 18.75 g l-1 of ethanol and xylitol, respectively, which were 5.11 and 5.71-fold higher than that of native. Ethanol yield, xylitol yield and specific sugar consumption rate obtained by the adapted cells were found to be 1.57, 1.65 and 4.84-fold higher than that of native yeast, respectively. Aforesaid results suggested that the evolutionary adaptation will be a very effective strategy in the near future for economic lignocellulosic ethanol production. PMID- 26886225 TI - Mitochondrial involvement in myocyte death and heart failure. AB - As the heart is an energy-demanding organ, impaired cardiac energy metabolism and mitochondrial function have been inexorably linked to cardiac dysfunction. There is a growing recognition that mitochondrial dysfunction contributes to impaired myocardial energetics and increased oxidative stress in cardiomyopathies, cardiac ischemic damage and heart failure (HF), and mitochondrial permeability transition pore opening has been reported a critical trigger of myocyte death and myocardial remodeling. It is well established that mitochondria play pivotal roles in intracellular signaling in both cell death as well as in cardioprotective pathways. Moreover, recent studies have shown that defects in mitochondrial dynamics affecting biogenesis and turnover are linked to cardiac senescence and HF. Accordingly, there has been an increasing interest in targeting mitochondria for HF therapy. This article reviews the background and recent evidence of mitochondrial involvement in several types of cell death (apoptosis, necrosis and autophagy) occurring in HF. In addition, potential strategies for targeting mitochondria are examined, and their utility in HF therapy considered. PMID- 26886226 TI - Cell death in the pathogenesis and progression of heart failure. PMID- 26886224 TI - A Panel of Stably Expressed Reference Genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos). AB - Determining which reference genes have the highest stability, and are therefore appropriate for normalising data, is a crucial step in the design of real-time quantitative PCR (qPCR) gene expression studies. This is particularly warranted in non-model and ecologically important species for which appropriate reference genes are lacking, such as the mallard--a key reservoir of many diseases with relevance for human and livestock health. Previous studies assessing gene expression changes as a consequence of infection in mallards have nearly universally used beta-actin and/or GAPDH as reference genes without confirming their suitability as normalisers. The use of reference genes at random, without regard for stability of expression across treatment groups, can result in erroneous interpretation of data. Here, eleven putative reference genes for use in gene expression studies of the mallard were evaluated, across six different tissues, using a low pathogenic avian influenza A virus infection model. Tissue type influenced the selection of reference genes, whereby different genes were stable in blood, spleen, lung, gastrointestinal tract and colon. beta-actin and GAPDH generally displayed low stability and are therefore inappropriate reference genes in many cases. The use of different algorithms (GeNorm and NormFinder) affected stability rankings, but for both algorithms it was possible to find a combination of two stable reference genes with which to normalise qPCR data in mallards. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies in ducks. The fact that nearly all previous studies of the influence of pathogen infection on mallard gene expression have used a single, non-validated reference gene is problematic. The toolkit of putative reference genes provided here offers a solid foundation for future studies of gene expression in mallards and other waterfowl. PMID- 26886227 TI - Prevalence of human herpesvirus-8 among HIV-infected patients, intravenous drug users and the general population in Iran. AB - Studies looking at the frequency of human herpesvirus-8 (HHV-8) among Iranian blood donors have produced conflicting results. The aim of this study was to investigate the prevalence of HHV-8 DNA by using polymerase chain reaction methods among 168 healthy individuals, 60 intravenous drug users and 100 HIV infected patients from Iran. The prevalence of HHV-8 was significantly higher among intravenous drug users (13.3%) compared with the general population (3.6%; P=0.017). The HHV-8 genome was mostly detected among intravenous drug users who displayed high-risk sexual behaviours. Moreover, the HHV-8 genome was also detected in 8% of HIV-infected patients. The present study findings support the likelihood that the transmission of HHV-8 is via a sexual route in the Iranian population. PMID- 26886229 TI - The Meaning of Evidence-Based Treatments for Veterans With Posttraumatic Stress Disorder. PMID- 26886228 TI - Glycemic Control and Excess Cardiovascular Mortality in Type 1 Diabetes. AB - Diabetes mellitus is a chronic systemic disease with multiple complications ranging from microvascular to macrovascular diseases. Type 1 diabetes comprises 5 % of adults with diabetes in the US. This population is shown to be at increased risk of cardiovascular events and mortality. Intensive glycemic control has been consistently associated with decreased microvascular complications but trials on macrovascular benefit yielded mixed results over the years. Recent data from long term observational follow-up studies of major diabetes cardiovascular events and mortality are showing benefits that were not seen with the initial interventional trials. This article will review evidence on the effect of glycemic control on complications in diabetes mellitus with a focus on cardiovascular mortality in type 1 diabetes. PMID- 26886230 TI - Gait abnormalities in early rheumatoid arthritis with temporomandibular joint involvement. PMID- 26886231 TI - Severe Neonatal Anaemia, MRI Findings and Neurodevelopmental Outcome. AB - BACKGROUND AND OBJECTIVE: Severe neonatal anaemia can impair cerebral oxygen supply. Data on long-term outcomes following severe neonatal anaemia are scarce. METHODS: Clinical data and neurodevelopmental outcome of 49 (near) term infants with haemoglobin concentration after birth <6.0 mmol/l were retrospectively collected and analysed. In a subgroup of 28 patients, amplitude-integrated EEG was available and in 25 infants cerebral MRI was obtained. Infants were followed up at 14-35 months of age and assessed with the Griffiths Scale of Mental Development or Bayley Scale of Infant Development. RESULTS: Eighteen patients (37%) died during the neonatal period. In 25 patients MRI was performed. A predominant pattern of injury on MRI was seen in the basal ganglia and thalami in 7 patients (28%), whereas some form of white matter injury was present in 16 (64%) and a combination in 3 (12%). Follow-up data were available for 26 patients (84% of survivors). Formal assessment of neurodevelopmental outcome was performed in 20 of 31 (65%) infants who survived (median age: 19 months, range: 14-35). Sixteen infants (80%) had a developmental quotient appropriate for age in the first 2 years after birth. On motor outcome, 1 patient (5%) scored below average (Z-score -1.10). One patient developed cerebral palsy. CONCLUSION: Early neurodevelopmental outcome in surviving patients with severe neonatal anaemia was within the normal range in the majority of the survivors. MRI showed mild-to moderate white matter injury in two thirds of the infants. Prospectively collected data with a longer follow-up period are needed. PMID- 26886232 TI - Nitric oxide in fungi: is there NO light at the end of the tunnel? AB - Nitric oxide (NO) is a remarkable gaseous molecule with multiple and important roles in different organisms, including fungi. However, the study of the biology of NO in fungi has been hindered by the lack of a complete knowledge on the different metabolic routes that allow a proper NO balance, and the regulation of these routes. Fungi have developed NO detoxification mechanisms to combat nitrosative stress, which have been mainly characterized by their connection to pathogenesis or nitrogen metabolism. However, the progress on the studies of NO anabolic routes in fungi has been hampered by efforts to disrupt candidate genes that gave no conclusive data until recently. This review summarizes the different roles of NO in fungal biology and pathogenesis, with an emphasis on the alternatives to explain fungal NO production and the recent findings on the involvement of nitrate reductase in the synthesis of NO and its regulation during fungal development. PMID- 26886233 TI - PCNA-binding proteins in the archaea: novel functionality beyond the conserved core. AB - Sliding clamps play an essential role in coordinating protein activity in DNA metabolism in all three domains of life. In eukaryotes and archaea, the sliding clamp is PCNA (proliferating cell nuclear antigen). Across the diversity of the archaea PCNA interacts with a highly conserved set of proteins with key roles in DNA replication and repair, including DNA polymerases B and D, replication factor C, the Fen1 nuclease and RNAseH2, but this core set of factors is likely to represent a fraction of the PCNA interactome only. Here, I review three recently characterised non-core archaeal PCNA-binding proteins NusS, NreA/NreB and TIP, highlighting what is known of their interactions with PCNA and their functions in vivo and in vitro. Gaining a detailed understanding of the non-core PCNA interactome will provide significant insights into key aspects of chromosome biology in divergent archaeal lineages. PMID- 26886234 TI - Intra-ChIP: studying gene regulation in an intracellular pathogen. AB - Intracellular bacteria that reside within a host cell use a variety of strategies to exploit this unique niche. While these organisms are technically challenging to study in the context of an infected host cell, recent advances have led to an improved understanding of how the intracellular environment impacts bacterial gene expression. We recently demonstrated that chromatin immunoprecipitation (ChIP) can be used to quantify transcription factor binding in the obligate intracellular pathogen Chlamydia trachomatis within infected cells. Furthermore, we showed it was possible to experimentally modulate transcription factor binding while simultaneously measuring changes in transcription. Here we discuss these findings as well as other recent work that has used ChIP to study intracellular pathogens within infected cells. We also discuss technical considerations associated with this approach and its possible future applications. PMID- 26886235 TI - Nuclear medicine imaging of posttraumatic osteomyelitis. AB - INTRODUCTION: Early recognition of a possible infection and therefore a prompt and accurate diagnostic strategy is essential for a successful treatment of posttraumatic osteomyelitis (PTO). However, at this moment there is no single routine test available that can detect osteomyelitis beyond doubt and the performed diagnostic tests mostly depend on personal experience, available techniques and financial aspects. Nuclear medicine techniques focus on imaging pathophysiological changes which usually precede anatomical changes. Together with recent development in hybrid camera systems, leading to better spatial resolution and quantification possibilities, this provides new opportunities and possibilities for nuclear medicine modalities to play an important role in diagnosing PTO. AIM: In this overview paper the techniques and available literature results for PTO are discussed for the three most commonly used nuclear medicine techniques: the three phase bone scan (with SPECT-CT), white blood cell scintigraphy (also called leukocyte scan) with SPECT-CT and (18)F fluorodeoxyglucose (FDG)-PET/CT. Emphasis is on how these techniques are able to answer the diagnostic questions from the clinicians (trauma and orthopaedic surgeons) and which technique should be used to answer a specific question. Furthermore, three illustrative cases from clinical practice are described. PMID- 26886236 TI - Reproductive factors are associated with oesophageal cancer risk: results from a meta-analysis of observational studies. AB - To further evaluate the association between reproductive events and the development of oesophageal cancer, we searched relevant studies using electronic databases (PubMed, ISI Web of Science). Study-specific relative risks with corresponding 95% confidence intervals (CI) in all analyses were used and multiple summary relative risk (SRR) estimates were calculated. We carried out subgroup analyses and used meta-regression techniques to explore potential sources of heterogeneity. Sensitivity analysis was carried out to identify whether pooled results were influenced by individual studies and publication bias was assessed by Begg's funnel plots and the Egger regression asymmetry test. Fourteen studies were eligible for inclusion in the meta-analysis, summarizing a total of 3816 oesophageal cancer cases. We found that age at menopause (SRR=0.70; 95% CI: 0.51-0.95) and hormone replacement therapy (SRR=0.67; 95% CI: 0.56-0.81) had an association with a decreased risk of oesophageal cancer. A similar result was obtained for parity (SRR=0.79; 95% CI: 0.71-0.89) and ever breastfeeding (SRR=0.65; 95% CI: 0.43-0.97). In contrast, postmenopausal status was associated with increased risk (SRR=1.65; 95% CI: 1.28-2.14). No statistically significant link was found with other exposures. Our meta-analysis supports the substantial influence of reproductive factors, which could be causally linked to oesophageal cancer. PMID- 26886237 TI - Interactive effects of 9-cis-retinoic acid and androgen on proliferation, differentiation, and apoptosis of LNCaP prostate cancer cells. AB - 9-cis-Retinoic acid (9cRA), which binds to both retinoic acid receptors and retinoic X receptors, inhibits prostate cancer induction in rats and reduces growth of prostate cancer cells. However, the nature of this growth inhibition and the interactive influence of androgens are not well defined and are the subject of this report. LNCaP and PC-3 cells were cultured and treated with a range of 9cRA concentrations for 3-6 days in the absence or presence of 5alpha dehydrotestosterone. 9cRA inhibited cell proliferation in a dose-dependent manner, plateauing at 10 mol/l. Treatment of cells with 10 mol/l 9cRA inhibited 5alpha-dihydroxytestosterone (DHT)-stimulated proliferation, the effect of which was maximal at 10 mol/l DHT. Treatment of DHT (10 mol/l)-exposed cells with 9cRA caused a dose-dependent increase in prostate-specific antigen in the medium after 6 days, but not 3 days. 9cRA caused a dose-dependent increase in apoptotic cells stained with H33258 after 3 days, but not 6 days; however, on using flow cytometry, apoptosis was apparent at both 3 and 6 days. Flow cytometry also revealed interference of G0/G1 to S phase transition by 9cRA. Inhibition by 9cRA of anchorage-independent growth of PC-3 cells was also found; LNCaP cells did not grow colonies in soft agar. 9cRA inhibited growth and induced differentiation of human LNCaP prostate cancer cells in vitro and inhibited anchorage-independent growth of PC-3 cells. Because 9cRA and 13-cis-retinoic acid, which is retinoic acid receptor-selective, prevent prostate carcinogenesis in rats, and 13-cis retinoic acid also inhibits growth of human prostate cancer cells, the RAR is a potential molecular target for prostate cancer prevention and therapy. PMID- 26886238 TI - Associations of alcohol use disorders with esophageal and gastric cancers: a population-based study in Sweden. AB - Alcohol consumption is associated with squamous cell carcinoma of the esophagus, but little is known about whether alcohol consumption is associated with adenocarcinoma of the esophagus and gastric cancer, which we attempt to clarify in this study. Individuals with alcohol use disorders were identified from the nation-wide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios of esophageal and gastric cancers using those without alcohol use disorders (AUDs) as a reference. A total of 14 518 and 73 504 patients were diagnosed with esophageal and gastric cancers, separately, during the study period. The risk of esophageal cancer was significantly increased, with a standardized incidence ratio of 2.24 (95% confidence interval 2.08-2.41) among individuals with AUDs. Both squamous cell carcinoma and adenocarcinoma of the esophagus were increased (2.89 for squamous cell carcinoma and 1.20 for adenocarcinoma). The incidence of gastric cancer was significantly decreased and the decrease was even more prominant for corpus cancer compared with cardia cancer (0.57 vs. 0.82). In this retrospective cohort study, we found that AUDs were associated with an increased risk of both squamous cell carcinoma and adenocarcinoma of the esophagus, whereas individuals with AUDs had a lower risk of gastric cancer, especially for corpus cancer, which may be related to the eradication of Helicobacter pylori infection. However, the underlying mechanisms need to be explored in future studies. PMID- 26886239 TI - Design in mind: eliciting service user and frontline staff perspectives on psychiatric ward design through participatory methods. AB - BACKGROUND: Psychiatric ward design may make an important contribution to patient outcomes and well-being. However, research is hampered by an inability to assess its effects robustly. This paper reports on a study which deployed innovative methods to capture service user and staff perceptions of ward design. METHOD: User generated measures of the impact of ward design were developed and tested on four acute adult wards using participatory methodology. Additionally, inpatients took photographs to illustrate their experience of the space in two wards. Data were compared across wards. RESULTS: Satisfactory reliability indices emerged based on both service user and staff responses. Black and minority ethnic (BME) service users and those with a psychosis spectrum diagnosis have more positive views of the ward layout and fixtures. Staff members have more positive views than service users, while priorities of staff and service users differ. Inpatient photographs prioritise hygiene, privacy and control and address symbolic aspects of the ward environment. CONCLUSIONS: Participatory and visual methodologies can provide robust tools for an evaluation of the impact of psychiatric ward design on users. PMID- 26886240 TI - Association Between Gasdermin A and Gasdermin B Polymorphisms and Susceptibility to Adult and Childhood Asthma Among Jordanians. AB - INTRODUCTION: Gasdermin A (GSDMA) and gasdermin B (GSDMB) have been associated with childhood, and to a lesser extent with adult, asthma in many populations. AIMS: In this study, we investigated the association between GSDMA and GSDMB variants and the incidence of adult and childhood asthma among Jordanians. METHODS: Subjects were divided into two groups: adults and children. Within the adult group there were 129 asthma patients and 111 healthy controls. In the pediatric group there were 98 asthma patients and 112 healthy children. Gasdermin A (GSDMA) (rs7212938, T/G) and Gasdermin B (rs7216389, T/C) polymorphisms were genotyped using the PCR-RFLP method. Three analysis models were applied to the genotype data: co-dominant, dominant and recessive. RESULTS: An association between the GSDMB T/C single nucleotide polymorphism (SNP) genotype and the incidence of childhood asthma was found (< 0.05). GSDMB T/C SNP in children also showed a very high tendency toward significance with p = 0.0532 in the single locus analysis. In adults, no significant differences in the allelic frequencies of any of the SNPs analyzed were found between the case and control populations. At the haplotype level, GC haplotype was found to be associated with the risk of asthma in children while none of the tested haplotypes were found to be associated with asthma risk in adults. CONCLUSIONS: The findings of this study confirm the previously reported association between the GSDMB gene and the risk of childhood asthma. PMID- 26886241 TI - The Assessment of Diet Quality and Its Effects on Health Outcomes Pre-pregnancy and during Pregnancy. AB - Overweight and obesity pre pregnancy or during pregnancy is associated with an increased risk for maternal obstetric and fetal complications. Diet is one modifiable risk factor that women may be motivated to improve. General healthy eating guidelines, micronutrient sufficiency and macronutrient quantity and quality are important nutrition considerations pre and during pregnancy. With regards to specific nutrients, health authorities have recommendations for folate and/or iodine supplementation; but not consistently for iron and omega-3 despite evidence for their association with health outcomes. There are modest additional requirements for energy and protein, but not fat or carbohydrate, in mid-late pregnancy. Diet indices and dietary pattern analysis are additional tools or methodologies used to assess diet quality. These tools have been used to determine dietary intakes and patterns and their association with pregnancy complications and birth outcomes pre or during pregnancy. Women who may unnecessarily resist foods due to fear of food contamination from listeriosis and methylmercury may limit their diet quality and a balanced approached is required. Dietary intake may also vary according to certain population characteristics. Additional support for women who are younger, less educated, overweight and obese, from socially disadvantaged areas, smokers and those who unnecessarily avoid healthy foods, is required to achieve a higher quality diet and optimal lifestyle peri conception. PMID- 26886242 TI - Lifestyle in Reproductive Medicine. PMID- 26886243 TI - Low-Temperature Seebeck Coefficients for Polaron-Driven Thermoelectric Effect in Organic Polymers. AB - We report the results of electronic structure coupled to molecular dynamics simulations on organic polymers subject to a temperature gradient at low temperature regimes. The temperature gradient is introduced using a Langevin-type dynamics corrected for quantum effects, which are very important in these systems. Under this condition we were able to determine that in these no-impurity systems the Seebeck coefficient is in the range of 1-3 MUV/K. These results are in good agreement with reported experimental results under the same low temperature conditions. PMID- 26886244 TI - Excited-State Dynamics of DNA Duplexes with Different H-Bonding Motifs. AB - The excited-state dynamics of three distinct forms of the d(GC)9.d(GC)9 DNA duplex were studied by combined time-resolved infrared experiments and quantum mechanical calculations. In the B- and Z-forms, bases on opposite strands form Watson-Crick (WC) base pairs but stack differently because of salt-induced changes in backbone conformation. At low pH, the two strands associate by Hoogsteen (HG) base pairing. Ultraviolet-induced intrastrand electron transfer (ET) triggers interstrand proton transfer (PT) in the B- and Z-forms, but the PT pathway is blocked in the HG duplex. Despite the different decay mechanisms, a common excited-state lifetime of ~ 30 ps is observed in all three duplex forms. The ET-PT pathway in the WC duplexes and the solely intrastrand ET pathway in the HG duplex yield the same pair of pi-stacked radicals on one strand. Back ET between these radicals is proposed to be the rate-limiting step behind excited state deactivation in all three duplexes. PMID- 26886245 TI - Falls prevention education: Interprofessional training to enhance collaborative practice. AB - The gap between the complex health care needs of older adults and the availability of geriatrics-trained health care professionals is widening. Interprofessional education offers an opportunity to engage multiple professions in interactive learning and clinically relevant problem solving to achieve high quality patient-centered care. This article describes a project that engaged an interprofessional teaching team to support interprofessional practice teams to reduce falls in older adults via implementation of evidence-based practice guidelines. Ninety-five participants from 25 teams were trained on multiple strategies to decrease the risk of falls in older adults. The intervention facilitated increases in knowledge, confidence in skill performance, and team commitment to change practice patterns to support the health and safety of older adults. Findings suggest that community-based practices can successfully support the training of interprofessional teams and that training may lead to improved care processes and outcomes for older adults. PMID- 26886247 TI - Diagnostic accuracy of ultrasound, conventional radiography and synovial fluid analysis in the diagnosis of calcium pyrophosphate dihydrate crystal deposition disease. AB - OBJECTIVES: To assess the diagnostic performance of ultrasound (US), x-rays, and microscopic analysis of synovial fluid (SF) for calcium pyrophosphate dihydrate crystal deposition disease (CPPD) using histology as a reference standard. METHODS: We enrolled consecutive patients with osteoarthritis waiting to undergo knee replacement surgery. Each patient underwent US of the knee, focusing on menisci and the hyaline cartilage, the day before surgery. During surgery, SF, menisci and condyles were retrieved and examined microscopically. For the meniscus and cartilage microscopic analysis, 8 samples were collected from each specimen and knee radiographs, performed up to 3 months before surgery, were also assessed. A dichotomous score was given for the presence/absence of CPP for each method. Microscopic findings of the specimens were considered the reference standard. All the procedures followed were in accordance with the ethical standards of the local responsible committee. RESULTS: 42 patients (14 males) were enrolled. All patients underwent US, 34 had eligible radiographs and 32 had SF analysis. 25 patients (59.5%) were positive for CPP at US, 15 (44.1%) at X-ray and 14 (43.7%) at SF. Sensitivity and specificity values were 96% and 87% for US, 75% and 93% for radiography and 77% and 100% for SF respectively. There were no statistically significant differences between the diagnostic performance across single tests. CONCLUSIONS: US proved to be at least as accurate as SF analysis for the diagnosis of CPPD. US, which is feasible and harmless, could be considered the first exam of choice for CPPD diagnosis. PMID- 26886248 TI - The Brunnsviken Brief Quality of Life Scale (BBQ): Development and Psychometric Evaluation. AB - Measurements of subjective quality of life (QoL) are an important complement to symptom ratings in clinical research and practice. Despite there being several established QoL self-rating scales, we identified a need for a freely accessible, easy-to-use inventory, validated for use with both clinical and non-clinical samples, based on the overall life satisfaction conceptualization of QoL. The Brunnsviken Brief Quality of life scale (BBQ) was designed to meet these requirements. Items were selected by performing a factor analysis on a large data set of QoL ratings collected previously. Six life areas (Leisure time, View on life, Creativity, Learning, Friends and Friendship, and View of self) were identified as important for overall QoL and were included in the BBQ. A psychometric evaluation was performed using two independent samples: healthy undergraduate students (n = 163), and a sample seeking treatment for social anxiety disorder (n = 568). Results suggested a unifactorial structure, with good concurrent and convergent validity, high internal and test-retest reliability, and accurate classification ability. We conclude that the BBQ is a valid and reliable measure of subjective QoL for use in clinical and research settings. The BBQ is presently available in 31 languages and can be freely downloaded from www.bbqscale.com . PMID- 26886246 TI - Face perception and learning in autism spectrum disorders. AB - Autism Spectrum Disorder (ASD) is characterized by impairment in social communication and restricted and repetitive interests. While not included in the diagnostic characterization, aspects of face processing and learning have shown disruptions at all stages of development in ASD, although the exact nature and extent of the impairment vary by age and level of functioning of the ASD sample as well as by task demands. In this review, we examine the nature of face attention, perception, and learning in individuals with ASD focusing on three broad age ranges (early development, middle childhood, and adolescence/adulthood). We propose that early delays in basic face processing contribute to the atypical trajectory of social communicative skills in individuals with ASD and contribute to poor social learning throughout development. Face learning is a life-long necessity, as the social world of individual only broadens with age, and thus addressing both the source of the impairment in ASD as well as the trajectory of ability throughout the lifespan, through targeted treatments, may serve to positively impact the lives of individuals who struggle with social information and understanding. PMID- 26886250 TI - Fluorescent Peptoids as Selective Live Cell Imaging Probes. AB - This paper describes the synthesis of fluorescent peptoids using the Ugi multicomponent reaction (4CR). The four synthesized structures had their photophysical properties evaluated and their potential as biomarkers established. The peptidomimetics were used at very low concentrations (10 nM) to follow their internalization in breast cancer cells and had their localization precisely determined. One of the new peptoids displayed mitochondrial affinity and stained this important organelle selectively. Co-staining experiments using MitoTracker Red confirmed the localization inside live cells. PMID- 26886249 TI - Association of Breast Conservation Surgery for Cancer With 90-Day Reoperation Rates in New York State. AB - IMPORTANCE: For early-stage breast cancer, breast conservation surgery (BCS) is a conservative option for women and involves removing the tumor with a margin of surrounding breast tissue. If margins are not tumor free, patients undergo additional surgery to avoid local recurrence. OBJECTIVES: To investigate the use of BCS in New York State and to determine rates of reoperation, procedure choice, and the effect of surgeon experience on the odds of a reoperation 90 days after BCS. DESIGN, SETTING, AND PARTICIPANTS: A population-based sample of 89 448 women undergoing primary BCS for cancer were selected and examined from January 1, 2003, to December 31, 2013, in New York State mandatory reporting databases. All hospitals and ambulatory surgery centers in New York State were included. Data were analyzed from December 15, 2014, to November 1, 2015. MAIN OUTCOMES AND MEASURES: Rate of reoperations within 90 days of the initial BCS procedure. RESULTS: During the study period, 89 448 women 20 years or older (mean [SD] age, 61.7 [13.7] years) underwent primary BCS. In 2013, 1416 women in New York aged 20 to 49 years underwent BCS compared with 3068 women aged 50 to 64 years and 3644 women 65 years or older. These numbers represent a significant decrease from 1960 women younger than 50 years in 2003 who underwent BCS (P < .001 for trend) but little change from the 2899 women aged 50 to 64 years and 3270 women 65 years or older who underwent BCS in 2003. Mean overall rate of 90-day reoperation was 30.9% (27 010 of 87 499 patients) and decreased over time from 39.5% (6630 of 16 805 patients) in 2003 to 2004 to 23.1% (5148 of 22 286 patients) in 2011 to 2013. Rates of reoperation were highest in women aged 20 to 49 years (37.7% [6990 of 18 524]) and lowest in women 65 years or older (26.3% [9656 of 36 691]) (P < .001 for trend). Over time, more patients underwent BCS as a subsequent procedure, from 4237 of 6630 patients (63.9%) in 2003 to 2004 to 4258 of 5148 (82.7%) in 2011 to 2013 (P < .001 for trend). Among the 19 466 women who underwent BCS as a second procedure, 2429 (12.5%) required a third intervention (2.7% of all women included). Significant surgeon-level variation was found in the data; 90-day rates of reoperations by surgeon ranged from 0% to 100%. Low-volume surgeons (<14 cases per year) had an unadjusted rate of 35.2% compared with 29.6% in middle volume (14-33 cases per year) and 27.5% in high-volume (>=34 cases per year) surgeons. The difference persisted in adjusted analyses (odds ratio for low volume surgeons, 1.49 [95% CI, 1.19-1.87]; for middle-volume surgeons, 1.20 [95% CI, 0.93-1.56]) compared with high-volume surgeons (used as the reference category). CONCLUSIONS AND RELEVANCE: Use of BCS has decreased overall, most steeply in younger women. Nearly 1 in 4 women underwent a reoperation within 90 days of BCS across New York State from 2011 to 2013, compared with 2 in 5 from 2003 to 2004. Rates vary significantly by surgeon, and initial BCS performed by high-volume surgeons was associated with a 33% lower risk for a reoperation. PMID- 26886251 TI - Prescription Psychostimulant Use Among Young Adults: A Narrative Review of Qualitative Studies. AB - BACKGROUND: Within the last decade, the nonmedical use of prescription drugs has raised concern, particularly among young adults. Psychostimulants, that is to say amphetamine and its derivatives, are pharmaceuticals, which contribute to what has come to be known in Canada and the United States as the "prescription drug crisis." Research in the fields of public health, addiction studies, and neuroethics has attempted to further understand this mounting issue; however, there is a paucity of data concerning the underlying social logics related to the use of these substances. OBJECTIVES: The objective of this article is to provide an overview of the current literature related to the social context of prescription psychostimulant use among young adults, and to discuss theoretical considerations as well as implications for future research. METHODS: A narrative review of the literature was performed. RESULTS: We found that research efforts have chiefly targeted college students, yet there is a lack of knowledge concerning other social groups likely to use these pharmaceuticals nonmedically, such as persons with high strain employment. Three main emerging patterns related to prescription psychostimulant use were identified: (1) control of external stressors, (2) strategic use toward the making of the self, and (3) increasing one's performance. CONCLUSIONS: Prescription psychostimulant use among young adults is anchored in contemporary normativity and cannot be separated from the developing performance ethic within North-American and other Western societies. We suggest that pharmaceuticalization and Actor-Network Theory are useful conceptual tools to frame future research efforts. PMID- 26886252 TI - Workplace mobbing: How the victim's coping behavior influences bystander responses. AB - Victims of workplace mobbing show diverse coping behavior. We investigated the impact of this behavior on bystander cognitions, emotions, and helping toward the victim, integrating coping literature with attribution theory. Adult part-time university students (N = 161) working at various organizations participated in a study with a 3(Coping: approach/avoidance/neutral) * 2(Gender Victim: male/female) * 2(Gender Bystander: male/female) design. Victims showing approach (vs. avoidance) coping were considered to be more self-reliant and less responsible for the continuation of the mobbing, and they elicited less anger. Continuation responsibility and self-reliance mediated the relationship between the victim's coping behavior and bystanders' helping intentions. Female (vs. male) participants reported more sympathy for the victim and greater willingness to help, and female (vs. male) victims elicited less anger. Theoretical and practical implications of the findings are discussed. PMID- 26886253 TI - Elemental composition of game meat from Austria. AB - Concentrations of 26 elements (B, Na, Mg, P, S, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sb, Ba, Hg, Pb, U) in wild game meat from Austria were analysed using an inductively coupled plasma mass spectrometer. All investigated animals were culled during the hunting season 2012/2013, including 10 chamois (Rupicapra rupicapra), 9 hare (Lepus europaeus), 10 pheasant (Phasianus colchicus), 10 red deer (Cervus elaphus), 12 roe deer (Capreolus capreolus) and 10 wild boar (Sus scrofa). In 19 out of 61 meat samples lead concentrations were higher than 0.1 mg/kg, the maximum limit in meat as set by the European Commission (Regulation EC No 1881/2006), which is most likely caused by ammunition residues. Especially, pellet shot animals and chamois show a high risk for lead contamination. Despite ammunition residues all investigated muscle samples show no further health risk with respect to metal contamination. PMID- 26886254 TI - NOx Emissions from Diesel Passenger Cars Worsen with Age. AB - Commonly, the NOx emissions rates of diesel vehicles have been assumed to remain stable over the vehicle's lifetime. However, there have been hardly any representative long-term emission measurements. Here we present real-driving emissions of diesel cars and light commercial vehicles sampled on-road over 15 years in Zurich/Switzerland. Results suggest deterioration of NOx unit emissions for Euro 2 and Euro 3 diesel technologies, while Euro 1 and Euro 4 technologies seem to be stable. We can exclude a significant influence of high-emitting vehicles. NOx emissions from all cars and light commercial vehicles in European emission inventories increase by 5-10% accounting for the observed deterioration, depending on the country and its share of diesel cars. We suggest monitoring the stability of emission controls particularly for high-mileage light commercial as well as heavy-duty vehicles. PMID- 26886255 TI - Transition State Structure of RNA Depurination by Saporin L3. AB - Saporin L3 from the leaves of the common soapwort is a catalyst for hydrolytic depurination of adenine from RNA. Saporin L3 is a type 1 ribosome inactivating protein (RIP) composed only of a catalytic domain. Other RIPs have been used in immunotoxin cancer therapy, but off-target effects have limited their development. In the current study, we use transition state theory to understand the chemical mechanism and transition state structure of saporin L3. In favorable cases, transition state structures guide the design of transition state analogues as inhibitors. Kinetic isotope effects (KIEs) were determined for an A14C mutant of saporin L3. To permit KIE measurements, small stem-loop RNAs that contain an AGGG tetraloop structure were enzymatically synthesized with the single adenylate bearing specific isotopic substitutions. KIEs were measured and corrected for forward commitment to obtain intrinsic values. A model of the transition state structure for depurination of stem-loop RNA (5'-GGGAGGGCCC-3') by saporin L3 was determined by matching KIE values predicted via quantum chemical calculations to a family of intrinsic KIEs. This model indicates saporin L3 displays a late transition state with the N-ribosidic bond to the adenine nearly cleaved, and the attacking water nucleophile weakly bonded to the ribosyl anomeric carbon. The transition state retains partial ribocation character, a feature common to most N ribosyl transferases. However, the transition state geometry for saporin L3 is distinct from ricin A-chain, the only other RIP whose transition state is known. PMID- 26886258 TI - Tuberculosis Caused by Mycobacterium africanum, United States, 2004-2013. AB - Mycobacterium africanum is endemic to West Africa and causes tuberculosis (TB). We reviewed reported cases of TB in the United States during 2004-2013 that had lineage assigned by genotype (spoligotype and mycobacterial interspersed repetitive unit variable number tandem repeats). M. africanum caused 315 (0.4%) of 73,290 TB cases with lineage assigned by genotype. TB caused by M. africanum was associated more with persons from West Africa (adjusted odds ratio [aOR] 253.8, 95% CI 59.9-1,076.1) and US-born black persons (aOR 5.7, 95% CI 1.2-25.9) than with US-born white persons. TB caused by M. africanum did not show differences in clinical characteristics when compared with TB caused by M. tuberculosis. Clustered cases defined as >2 cases in a county with identical 24 locus mycobacterial interspersed repetitive unit genotypes, were less likely for M. africanum (aOR 0.1, 95% CI 0.1-0.4), which suggests that M. africanum is not commonly transmitted in the United States. PMID- 26886256 TI - Embryonic Stem Cell (ES)-Specific Enhancers Specify the Expression Potential of ES Genes in Cancer. AB - Cancers often display gene expression profiles resembling those of undifferentiated cells. The mechanisms controlling these expression programs have yet to be identified. Exploring transcriptional enhancers throughout hematopoietic cell development and derived cancers, we uncovered a novel class of regulatory epigenetic mutations. These epimutations are particularly enriched in a group of enhancers, designated ES-specific enhancers (ESSEs) of the hematopoietic cell lineage. We found that hematopoietic ESSEs are prone to DNA methylation changes, indicative of their chromatin activity states. Strikingly, ESSE methylation is associated with gene transcriptional activity in cancer. Methylated ESSEs are hypermethylated in cancer relative to normal somatic cells and co-localized with silenced genes, whereas unmethylated ESSEs tend to be hypomethylated in cancer and associated with reactivated genes. Constitutive or hematopoietic stem cell-specific enhancers do not show these trends, suggesting selective reactivation of ESSEs in cancer. Further analyses of a hypomethylated ESSE downstream to the VEGFA gene revealed a novel regulatory circuit affecting VEGFA transcript levels across cancers and patients. We suggest that the discovered enhancer sites provide a framework for reactivation of ES genes in cancer. PMID- 26886259 TI - The Mutational Landscape of Acute Promyelocytic Leukemia Reveals an Interacting Network of Co-Occurrences and Recurrent Mutations. AB - Preliminary Acute Promyelocytic Leukemia (APL) whole exome sequencing (WES) studies have identified a huge number of somatic mutations affecting more than a hundred different genes mainly in a non-recurrent manner, suggesting that APL is a heterogeneous disease with secondary relevant changes not yet defined. To extend our knowledge of subtle genetic alterations involved in APL that might cooperate with PML/RARA in the leukemogenic process, we performed a comprehensive analysis of somatic mutations in APL combining WES with sequencing of a custom panel of targeted genes by next-generation sequencing. To select a reduced subset of high confidence candidate driver genes, further in silico analysis were carried out. After prioritization and network analysis we found recurrent deleterious mutations in 8 individual genes (STAG2, U2AF1, SMC1A, USP9X, IKZF1, LYN, MYCBP2 and PTPN11) with a strong potential of being involved in APL pathogenesis. Our network analysis of multiple mutations provides a reliable approach to prioritize genes for additional analysis, improving our knowledge of the leukemogenesis interactome. Additionally, we have defined a functional module in the interactome of APL. The hypothesis is that the number, or the specific combinations, of mutations harbored in each patient might not be as important as the disturbance caused in biological key functions, triggered by several not necessarily recurrent mutations. PMID- 26886257 TI - A Mechanism to Enhance Cellular Responsivity to Hormone Action: Kruppel-Like Factor 9 Promotes Thyroid Hormone Receptor-beta Autoinduction During Postembryonic Brain Development. AB - Thyroid hormone (TH) receptor (TR)-beta (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Kruppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRbeta in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs. PMID- 26886260 TI - Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis. AB - PURPOSE: To discover novel prognostic biomarkers in ovarian serous carcinomas. METHODS: A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer's method and selected for statistical significance with a false discovery rate (FDR) <.05 using the Benjamini-Hochberg method. RESULTS: Twelve genes with high mRNA expression were prognostic of poor outcome with an FDR <.05 (AXL, APC, RAB11FIP5, C19orf2, CYBRD1, PINK1, LRRN3, AQP1, DES, XRCC4, BCHE, and ASAP3). Twenty genes with low mRNA expression were prognostic of poor outcome with an FDR <.05 (LRIG1, SLC33A1, NUCB2, POLD3, ESR2, GOLPH3, XBP1, PAXIP1, CYB561, POLA2, CDH1, GMNN, SLC37A4, FAM174B, AGR2, SDR39U1, MAGT1, GJB1, SDF2L1, and C9orf82). CONCLUSION: A meta-analysis of all single genes identified thirty two candidate biomarkers for their possible role in ovarian serous carcinoma. These genes can provide insight into the drivers or regulators of ovarian cancer and should be evaluated in future studies. Genes with high expression indicating poor outcome are possible therapeutic targets with known antagonists or inhibitors. Additionally, the genes could be combined into a prognostic multi gene signature and tested in future ovarian cohorts. PMID- 26886261 TI - Psychological and behavioral interventions to reduce HIV risk: evidence from a randomized control trial among orphaned and vulnerable adolescents in South Africa. AB - Evidence-based approaches are needed to address the high levels of sexual risk behavior and associated HIV infection among orphaned and vulnerable adolescents. This study recruited adolescents from a support program for HIV-affected families and randomly assigned them by cluster to receive one of the following: (1) a structured group-based behavioral health intervention; (2) interpersonal psychotherapy group sessions; (3) both interventions; or (4) no new interventions. With 95% retention, 1014 adolescents were interviewed three times over a 22-month period. Intent-to-treat analyses, applying multivariate difference-in-difference probit regressions, were performed separately for boys and girls to assess intervention impacts on sexual risk behaviors. Exposure to a single intervention did not impact behaviors. Exposure to both interventions was associated with risk-reduction behaviors, but the outcomes varied by gender: boys reported fewer risky sexual partnerships (beta = -.48, p = .05) and girls reported more consistent condom (beta = 1.37, p = .02). There was no difference in the likelihood of sexual debut for either gender. Providing both psychological and behavioral interventions resulted in long-term changes in sexual behavior that were not present when either intervention was provided in isolation. Multifaceted approaches for reducing sexual risk behaviors among vulnerable adolescents hold significant promise for mitigating the HIV epidemic among this priority population. PMID- 26886263 TI - Chemotherapy Modulates Intestinal Immune Gene Expression Including Surfactant Protein-D and Deleted in Malignant Brain Tumors 1 in Piglets. AB - BACKGROUND: Information about chemotherapy-induced intestinal gene expression may provide insight into the mechanisms underlying gut toxicity and help identify biomarkers and targets for intervention. METHODS: We analyzed jejunal tissue from piglets subjected to two different, clinically relevant chemotherapy regimens: (1) busulfan plus cyclophosphamide (BUCY) and (2) doxorubicin (DOX). RESULTS: Gene expression analysis identified 1,328 differentially expressed genes in the BUCY piglets and 594 in the DOX piglets, compared to controls. Similar changes in expression were found for 137 genes across the BUCY and DOX piglets. Selected genes of potential biological significance with a similar change in expression across the treatments were controlled by real-time polymerase chain reaction. Key innate defense molecules, including surfactant protein-D and deleted in malignant brain tumors 1, were among the upregulated genes for both treatments. CONCLUSION: In the developing intestine, chemotherapy increases the expression of genes related to innate immune functions involved in surveillance, protection, and homeostasis of mucosal surfaces. PMID- 26886262 TI - The Effects of 52 Weeks of Soccer or Resistance Training on Body Composition and Muscle Function in +65-Year-Old Healthy Males--A Randomized Controlled Trial. AB - The effects of 52 weeks of soccer or resistance training were investigated in untrained elderly men. The subjects aged 68.1+/-2.1 yrs were randomised into a soccer (SG; n = 9), a resistance (RG; n = 9) and a control group (CG; n = 8). The subjects in SG and RG, respectively, trained 1.7+/-0.3 and 1.8+/-0.3 times weekly on average during the intervention period. Muscle function and body composition were determined before and after 16 and 52 weeks of the intervention period. In SG, BMI was reduced by 1.5% and 3.0% (p<0.05) after 16 and 52 weeks, respectively, unchanged in RG and 2% higher (p<0.05) in CG after 52 weeks of the intervention period. In SG, the response to a glucose tolerance test was 16% lower (p<0.05) after 16 wks, but not after 52 wks, compared to before the intervention period, and unchanged in RG and CG. In SG, superoxide dismutase-2 expression was 59% higher (p<0.05) after 52 wks compared to before the intervention period, and unchanged in RG and CG. In RG, upper body lean mass was 3 and 2% higher (p<0.05) after 16 and 52 wks, respectively, compared to before the intervention period, and unchanged in SG and CG. In RG, Akt-2 expression increased by 28% (p<0.01) and follistatin expression decreased by 38% (p<0.05) during the 52-wk intervention period, and was unchanged in SG and CG. Thus, long term soccer training reduces BMI and improves anti-oxidative capacity, while long term resistance training impacts muscle protein enzyme expression and increases lean body mass in elderly men. Trial Registration: ClinicalTrials.gov: NCT01530035. PMID- 26886264 TI - Ethnicity and detention: are Black and minority ethnic (BME) groups disproportionately detained under the Mental Health Act 2007? AB - PURPOSE: There is substantial evidence to suggest that Black and minority ethnic (BME) patients are disproportionately detained under the Mental Health Act (MHA). We examined ethnic differences in patients assessed for detention and explored the effect of ethnicity after controlling for confounders. METHODS: A prospective study of all MHA assessments conducted in 1 year (April 2009-March 2010) within Birmingham and Solihull Mental Health Foundation Trust, UK. Proportion of assessments and detentions within denominator population of service users and regional populations were calculated. Multiple regression analysis was conducted to determine which variables were associated with the outcome of MHA assessment and the role of ethnicity. RESULTS: Of the 1115 assessments, 709 led to detentions (63.58 %). BME ethnic groups were statistically more likely to be assessed and detained under the MHA as compared to Whites, both in the service user and the ethnic population estimates in Birmingham, UK. MHA detention was predicted by having a serious mental illness, the presence of risk, older age and living alone. Ethnicity was not associated with detention under the MHA with age, diagnosis, risk and level of social support accounted for. CONCLUSION: The BME 'disproportionality' in detention rates seems to be due to higher rates of mental illness, greater risk and poorer levels of social support rather than ethnicity per se. PMID- 26886266 TI - Voting Intention and Choices: Are Voters Always Rational and Deliberative? AB - Human rationality--the ability to behave in order to maximize the achievement of their presumed goals (i.e., their optimal choices)--is the foundation for democracy. Research evidence has suggested that voters may not make decisions after exhaustively processing relevant information; instead, our decision-making capacity may be restricted by our own biases and the environment. In this paper, we investigate the extent to which humans in a democratic society can be rational when making decisions in a serious, complex situation-voting in a local political election. We believe examining human rationality in a political election is important, because a well-functioning democracy rests largely upon the rational choices of individual voters. Previous research has shown that explicit political attitudes predict voting intention and choices (i.e., actual votes) in democratic societies, indicating that people are able to reason comprehensively when making voting decisions. Other work, though, has demonstrated that the attitudes of which we may not be aware, such as our implicit (e.g., subconscious) preferences, can predict voting choices, which may question the well-functioning democracy. In this study, we systematically examined predictors on voting intention and choices in the 2014 mayoral election in Taipei, Taiwan. Results indicate that explicit political party preferences had the largest impact on voting intention and choices. Moreover, implicit political party preferences interacted with explicit political party preferences in accounting for voting intention, and in turn predicted voting choices. Ethnic identity and perceived voting intention of significant others were found to predict voting choices, but not voting intention. In sum, to the comfort of democracy, voters appeared to engage mainly explicit, controlled processes in making their decisions; but findings on ethnic identity and perceived voting intention of significant others may suggest otherwise. PMID- 26886267 TI - Making "cents" of the business side of nurse practitioner practice. AB - Nurse practitioners produce excellent patient outcomes and should be allowed to practice to the full extent of their education and training. In addition to clinical skills, nurse practitioners need to understand the business side of practice in order to ensure fair and equitable compensation. PMID- 26886265 TI - Transition from Bioinert to Bioactive Material by Tailoring the Biological Cell Response to Carboxylated Nanocellulose. AB - This work presents an insight into the relationship between cell response and physicochemical properties of Cladophora cellulose (CC) by investigating the effect of CC functional group density on the response of model cell lines. CC was carboxylated by electrochemical TEMPO-mediated oxidation. By varying the amount of charge passed through the electrolysis setup, CC materials with different degrees of oxidation were obtained. The effect of carboxyl group density on the material's physicochemical properties was investigated together with the response of human dermal fibroblasts (hDF) and human osteoblastic cells (Saos-2) to the carboxylated CC films. The introduction of carboxyl groups resulted in CC films with decreased specific surface area and smaller total pore volume compared with the unmodified CC (u-CC). While u-CC films presented a porous network of randomly oriented fibers, a compact and aligned fiber pattern was depicted for the carboxylated-CC films. The decrease in surface area and total pore volume, and the orientation and aggregation of the fibers tended to augment parallel to the increase in the carboxyl group density. hDF and Saos-2 cells presented poor cell adhesion and spreading on u-CC, which gradually increased for the carboxylated CC as the degree of oxidation increased. It was found that a threshold value in carboxyl group density needs be reached to obtain a carboxylated-CC film with cytocompatibility comparable to commercial tissue culture material. Hence, this study demonstrates that a normally bioinert nanomaterial can be rendered bioactive by carefully tuning the density of charged groups on the material surface, a finding that not only may contribute to the fundamental understanding of biointerface phenomena, but also to the development of bioinert/bioactive materials. PMID- 26886268 TI - The lead crisis in Flint, Michigan. PMID- 26886269 TI - Managing chronic pain in primary care. AB - At least 100 million adults in the United States are afflicted with chronic pain. Nurse practitioners and other providers are often challenged by the complexity of chronic pain management. This article discusses systematic strategies to facilitate safe, efficient, satisfactory, and quality care of patients with chronic pain in primary care. PMID- 26886270 TI - Acute kidney injury after cardiovascular surgery. AB - Acute kidney injury (AKI) is a complication experienced by many patients undergoing cardiovascular surgery. Postoperative deterioration in renal function is associated with an increased risk of in-hospital mortality and affects long term survival. Developing strategies to identify and treat AKI is important to reduce incidence and optimize outcomes. PMID- 26886272 TI - Integrating palliative care into primary care for patients with chronic, life limiting conditions. AB - As longevity increases, individuals with chronic, life-limiting conditions will live longer with disease burden and functional decline. Nurse practitioners can integrate symptom management, early decision-making, and supportive care into the primary care setting to improve quality of life and decrease economic and emotional impact at the end of life. PMID- 26886275 TI - Contrasting Inducible Knockdown of the Auxiliary PTEX Component PTEX88 in P. falciparum and P. berghei Unmasks a Role in Parasite Virulence. AB - Pathogenesis of malaria infections is linked to remodeling of erythrocytes, a process dependent on the trafficking of hundreds of parasite-derived proteins into the host erythrocyte. Recent studies have demonstrated that the Plasmodium translocon of exported proteins (PTEX) serves as the central gateway for trafficking of these proteins, as inducible knockdown of the core PTEX constituents blocked the trafficking of all classes of cargo into the erythrocyte. However, the role of the auxiliary component PTEX88 in protein export remains less clear. Here we have used inducible knockdown technologies in P. falciparum and P. berghei to assess the role of PTEX88 in parasite development and protein export, which reveal that the in vivo growth of PTEX88-deficient parasites is hindered. Interestingly, we were unable to link this observation to a general defect in export of a variety of known parasite proteins, suggesting that PTEX88 functions in a different fashion to the core PTEX components. Strikingly, PTEX88-deficient P. berghei were incapable of causing cerebral malaria despite a robust pro-inflammatory response from the host. These parasites also exhibited a reduced ability to sequester in peripheral tissues and were removed more readily from the circulation by the spleen. In keeping with these findings, PTEX88-deficient P. falciparum-infected erythrocytes displayed reduced binding to the endothelial cell receptor, CD36. This suggests that PTEX88 likely plays a specific direct or indirect role in mediating parasite sequestration rather than making a universal contribution to the trafficking of all exported proteins. PMID- 26886276 TI - Polysaccharide-based silver nanoparticles synthesized by Klebsiella oxytoca DSM 29614 cause DNA fragmentation in E. coli cells. AB - Silver nanoparticles (AgNPs), embedded into a specific exopolysaccharide (EPS), were produced by Klebsiella oxytoca DSM 29614 by adding AgNO3 to the cultures during exponential growth phase. In particular, under aerobic or anaerobic conditions, two types of silver nanoparticles, named AgNPs-EPS(aer) and the AgNPs EPS(anaer), were produced respectively. The effects on bacterial cells was demonstrated by using Escherichia coli K12 and Kocuria rhizophila ATCC 9341 (ex Micrococcus luteus) as Gram-negative and Gram-positive tester strains, respectively. The best antimicrobial activity was observed for AgNPs-EPS(aer), in terms of minimum inhibitory concentrations and minimum bactericidal concentrations. Observations by transmission electron microscopy showed that the cell morphology of both tester strains changed during the exposition to AgNPs EPS(aer). In particular, an electron-dense wrapped filament was observed in E. coli cytoplasm after 3 h of AgNPs-EPS(aer) exposition, apparently due to silver accumulation in DNA, and both E. coli and K. rhizophila cells were lysed after 18 h of exposure to AgNPs-EPS(aer). The DNA breakage in E. coli cells was confirmed by the comparison of 3-D fluorescence spectra fingerprints of DNA. Finally the accumulation of silver on DNA of E. coli was confirmed directly by a significant Ag(+) release from DNA, using the scanning electrochemical microscopy and the voltammetric determinations. PMID- 26886277 TI - Mechanisms of Asthma in Obesity. Pleiotropic Aspects of Obesity Produce Distinct Asthma Phenotypes. AB - The majority of patients with severe or difficult-to-control asthma in the United States are obese. Epidemiological studies have clearly established that obese patients tend to have worse asthma control and increased hospitalizations and do not respond to standard controller therapy as well as lean patients with asthma. Less clear are the mechanistic underpinnings for the striking clinical differences between lean and obese patients with asthma. Because obesity is principally a disorder of metabolism and energy regulation, processes fundamental to the function of every cell and system within the body, it is not surprising that it affects the respiratory system; it is perhaps surprising that it has taken so long to appreciate how dysfunctional metabolism and energy regulation lead to severe airway disease. Although early investigations focused on identifying a common factor in obesity that could promote airway disease, an appreciation has emerged that the asthma of obesity is a manifestation of multiple anomalies related to obesity affecting all the different pathways that cause asthma, and likely also to de novo airway dysfunction. Consequently, all the phenotypes of asthma currently recognized in lean patients (which are profoundly modified by obesity), as well as those unique to one's obesity endotype, likely contribute to obese asthma in a particular individual. This perspective reviews what we have learned from clinical studies and animal models about the phenotypes of asthma in obesity, which show how specific aspects of obesity and altered metabolism might lead to de novo airway disease and profoundly modify existing airway disease. PMID- 26886278 TI - Alcohol dehydrogenase and aldehyde dehydrogenase in malignant neoplasms. AB - According to International Agency for Research on Cancer, ethanol and acetaldehyde belong to group 1 of human carcinogens. The accurate mechanism by which alcohol consumption enhances carcinogenesis is still unexplained. Alcohol is oxidized primarily by alcohol dehydrogenase (ADH) to acetaldehyde, a substance capable of initiating carcinogenesis by forming adducts with proteins and DNA and causing mutations. Next, acetaldehyde is metabolized by aldehyde dehydrogenase (ALDH) to acetate. In tissues of many cancers, we can observe significantly higher activity of total alcohol dehydrogenase with any change in aldehyde dehydrogenase activity in comparison with healthy cells. Moreover, in malignant diseases of digestive system, significantly increased activity of ADH isoenzymes class I, III and IV was found. The gynecological, brain and renal cancers exhibit increased activity of class I ADH. ADH and ALDH can play also a crucial regulatory role in initiation and progression of malignant diseases by participation in retinoic acid synthesis and elimination of toxic acetaldehyde. Besides, changes of enzymes activities in tumor cells are reflected in serum of cancer patients, which create the possibilities of application ADH isoenzymes as cancer markers. PMID- 26886279 TI - Non-random spatial relationships between mast cells and microvessels in human endometrial carcinoma. AB - Mast cells (MCs) accumulate in the stroma surrounding tumors, where they secrete angiogenic cytokines and proteases, and an increased number of MCs have been demonstrated in angiogenesis associated with solid and hematological tumors. The aim of this study is to contribute to the knowledge of distribution of MCs in tumors, investigating the pattern of distribution of tryptase-positive MCs around the blood vessels in human endometrial carcinoma samples by introducing a quantitative approach to characterize their spatial distribution. The results have shown that in human endometrial cancer bioptic specimens the spatial distribution of MCs shows significant deviation from randomness as compared with control group in which, instead, the spatial distribution of MCs is consistent with a random distribution. These findings confirm that MCs enhance tumor angiogenesis and their preferential localization along blood vessels and sites of new vessel formation sustaining the suggestion for an association between MCs and angiogenesis. However, this spatial association between vessels and MCs might simply reflect migrating MCs from the blood stream at vessel growing sites. PMID- 26886280 TI - Necessary circumferential resection margins to prevent rectal cancer relapse after abdomino-peranal (intersphincteric) resection. AB - PURPOSE: The purpose of this study was to determine the adequate circumferential resection margin (CRM) for abdomino-peranal (intersphincteric) resection (ISR) that would prevent the relapse of rectal cancers. METHODS: The records of 41 cases that underwent curative ISR for rectal cancer were retrospectively reviewed. The relapse-free survival rates and overall survival rates were evaluated and correlated with the maximum depth of the inner muscularis layer reached during ISR (i.e., the radial margin [RM] and distal margin [DM]). Cases were divided into three groups based on the sizes of the RM and DM: (1) group A (RM >2 mm and DM >1.5 cm), (2) group B (RM >2 mm or DM >1.5 cm but not both), and (3) group C (RM <2 mm and DM <1.5 cm). RESULTS: The relapse-free survival rates of the cases in group C were lower than those in the cases of group A or group B (p = 0.002 and 0.037, respectively). The resection margins required to prevent rectal cancer relapse were >2 mm for the RM and >1.5 cm for the DM. For these margins, the intersphincteric space had to be entered (i.e., between the internal and external anal sphincters). CONCLUSION: It is critical to enter the intersphincteric space to ensure an adequate CRM (RM >2 mm and DM >1.5 cm) for preventing rectal cancer recurrence after ISR. PMID- 26886281 TI - Recurrent laryngeal nerve injury with incomplete loss of electromyography signal during monitored thyroidectomy-evaluation and outcome. AB - PURPOSE: During monitored thyroidectomy, a partially or completely disrupted point of nerve conduction on the exposed recurrent laryngeal nerve (RLN) indicates true electrophysiologic nerve injury. Complete loss of signal (LOS; absolute threshold value <100 MUV) at the end of operation often indicates a postoperative vocal cord (VC) palsy. However, the evaluation for the injured RLN with incomplete LOS and its functional outcome has not been well described. METHODS: Three hundred twenty-three patients with 522 RLNs at risk who underwent standardized monitored thyroidectomy were enrolled. The RLN was routinely stimulated at the most proximal (R2p signal) and distal (R2d signal) ends of exposure after thyroid resection to determine if there was an injured point on the RLN. Pre- and postoperative VC function was routinely examined. RESULTS: Twenty-nine RLNs (5.6 %) were detected with an injury point. Five nerves had complete LOS and other 24 nerves had incomplete LOS where the R2p/R2d reduction (% of amplitude reduction compared with proximal to distal RLN stimulation) ranged from 22 to 79 %. Postoperative temporary VC palsy was noted in those five RLNs with complete LOS (final vagal signal, V2 < 100 MUV) and four RLNs with incomplete LOS (R2p/R2d reduction 62-79 %; V2 181-490 MUV). In the remaining 20 nerves with R2p/R2d reduction <=53 % (V2 373-1623 MUV), all showed normal VC mobility. Overall, false negative results were found in two RLNs (0.4 %) featuring unchanged V2 and R2p/R2d but developed VC palsy. CONCLUSIONS: Testing and comparing the R2p/R2d signal is a simple and useful procedure to evaluate RLN injury after its dissection and predict functional outcome. When the relative threshold value R2p/R2d reduction reaches over 60 %, surgeon should consider the possibility of postoperative VC palsy. PMID- 26886282 TI - Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation. AB - Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that can promote antitumor immunity when pulsed with tumor antigens and then matured by stimulatory agents. Despite apparent progress in DC-based cancer immunotherapy, some discrepancies were reported in generating potent DCs. Listeria monocytogenes as an intracellular microorganism is able to effectively activate DCs through engaging pattern-recognition receptors (PRRs). This study aimed to find the most potent components derived from L. monocytogenes inducing DC maturation. The preliminary results demonstrated that the ability of protein components is higher than DNA components to promote DC maturation and activation. Protein lysate fractionation demonstrated that fraction 2 HIC (obtained by hydrophobic interaction chromatography) was able to efficiently mature DCs. F2HIC-matured DCs are able to induce allogeneic CD8(+) T cells proliferation better than LPS matured DCs and induce IFN-gamma producing CD8(+) T cells. Mass spectrometry results showed that F2HIC contains 109 proteins. Based on the bioinformatics analysis for these 109 proteins, elongation factor Tu (EF-Tu) could be considered as a PRR ligand for stimulating DC maturation. PMID- 26886283 TI - Fascin 1 promoted the growth and migration of non-small cell lung cancer cells by activating YAP/TEAD signaling. AB - Fascin 1 (Fascin actin-bundling protein 1) is an actin-binding protein. Although several studies have reported the dysregulation of Fascin 1 in non-small cell lung cancer (NSCLC), its functions in the progression of NSCLC and the related molecular mechanism were not fully understood. In this study, the expression of Fascin 1 in NSCLC tissues was determined using quantitative PCR (qPCR), and the roles of Fascin 1 in the progression of NSCLC were investigated. It was found that both the messenger RNA (mRNA) level and the protein level of Fascin 1 were upregulated in NSCLC tissues. Forced expression of Fascin 1 promoted the growth and migration of NSCLC cells, while knocking down the expression of Fascin 1 inhibited the growth, migration, and tumorigenesis of NSCLC cells. Mechanism studies showed that Fascin 1 increased the transcriptional activity of the YAP/TEAD (Yes-associated protein/TEA domain transcriptional factor) complex, and knocking down the expression of Fascin 1 attenuated the expression of target genes downstream the YAP/TEAD complex. In addition, MST1 interacted with Fascin 1. Taken together, Fascin 1 plays an oncogenic role in NSCLC by activating the transcriptional activity of the YAP/TEAD complex. PMID- 26886284 TI - Significance and evaluation of anaplastic lymphoma kinase by immunohistochemistry in non-small cell lung cancer. AB - We used immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) to evaluate anaplastic lymphoma kinase (ALK) protein expression and gene rearrangements, respectively, in 283 cases of wild-type epidermal growth factor receptor (EGFR) non-small cell lung cancer biopsy specimens. Immunohistochemistry was positive for ALK in 52 cases (18.4 %), and there was no significant difference in staining between various monoclonal antibodies (Roche ALK test kit, D5F3, p-ALK, and EML4-ALK). On RT-PCR, 36 cases (12.7 %) were positive for ALK. Immunohistochemistry and RT-PCR were both positive in 35 cases and both negative in 230 cases, and both have a high consistency (265/283, 93.6 %). Including 17 cases, immunohistochemistry was positive but RT-PCR was negative, and in one case, immunohistochemistry was negative but RT-PCR was positive. On fluorescence in situ hybridization (FISH) testing of these 18 cases, only three cases were positive (one RT-PCR was positive; two immunohistochemistry were positive). There is a high prevalence of ALK positivity in wild-type EGFR non-small cell lung cancer. Immunohistochemistry for the detection of ALK gene rearrangements was highly consistent with RT-PCR, and thus, it is a good screening tool but produces false positive results that necessitate further screening by RT-PCR or FISH. PMID- 26886285 TI - TNFAIP8 overexpression: a potential predictor of lymphatic metastatic recurrence in pN0 esophageal squamous cell carcinoma after Ivor Lewis esophagectomy. AB - Esophageal squamous cell carcinoma (ESCC) has a poor prognosis due to high lymphatic metastatic recurrence rates after Ivor Lewis esophagectomy. We sought to investigate the correlation between tumor necrosis factor alpha-induced protein 8 (TNFAIP8) expression and postoperative lymphatic recurrence in patients with pN0 ESCC. One hundred twenty-two patients with pN0 ESCC undergoing Ivor Lewis esophagectomy were enrolled in this study. TNFAIP8 overexpression was found in 73 (59.8 %) tumor specimens. The 3-year lymphatic metastatic recurrence rate among TNFAIP8-overexpressing patients was significantly higher than in TNFAIP8 negative patients (p = 0.003). Multivariate Cox regression identified TNFAIP8 overexpression as an independent risk factor for lymphatic recurrence (p = 0.048). TNFAIP8 messenger RNA (mRNA) levels were significantly higher in patients with lymphatic recurrence than in patients without tumor recurrence (p = 0.019). Stable silencing of TNFAIP8 expression in ESCC-derived cells (Eca109) reduced proliferation, motility, and invasion and induced apoptosis. In addition, transient silencing of TNFAIP8 expression decreased cell motility and invasion and increased apoptosis in a second ESCC-derived cell line (KYSE150). Taken together, these findings suggest that TNFAIP8 overexpression is a potential biomarker to identify pN0 ESCC patients at higher risk of lymphatic recurrence who may benefit from adjuvant therapy. PMID- 26886286 TI - Association between p21 Ser31Arg polymorphism and the development of cervical lesion in women infected with high risk HPV. AB - Infection by high-risk human papillomavirus (HR-HPV) and single nucleotide polymorphism (SNP) in genes involved in cell cycle control, as p21 and p27, are important factors in the development of different types of human cancers. This study aims at investigating whether both the p21 Ser31Arg and p27 V109G polymorphisms are associated with susceptibility to the development of cervical lesions in women HR-HPV positive. We analyzed 132 women HPV positive and with cervical lesions or CC and 154 healthy control (HPV negative and without cervical lesions). p21 Ser31Arg and p27 V109G polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and sequencing. The p21 31Arg allele was associated with susceptibility for the development of cervical lesions (P* = 0.0009), while p27 V109G polymorphism showed no significant differences for this association (P* = 0.89). However, the combined effect of the polymorphisms showed that the presence of the CC genotype (SNP p21 Ser31Arg) conferred protection for the development of cervical lesions (OR = 0.39). p21 Ser31Arg and p27 V109G polymorphisms were not associated with the grade of cervical lesions (CINI, CINII, and CINIII) or CC (P* > 0.05). The HR-HPV more frequent in this study were of 16 (57.6 %) and 18 (37.1 %) types; however, no association was observed when both polymorphisms and risk factors analyzed were compared (P* > 0.05). Our findings suggest a possible association between p21 Ser31tabArg polymorphism and susceptibility to the development of cervical lesions in women from Pernambuco. Brazil. PMID- 26886288 TI - Aqueous Phase Synthesis of ZIF-8 Membrane with Controllable Location on an Asymmetrically Porous Polymer Substrate. AB - In this study, we have demonstrated a simple, scalable, and environmentally friendly route for controllable fabrication of continuous, well-intergrown ZIF-8 on a flexible polymer substrate via contra-diffusion method in conjunction with chemical vapor modification of the polymer surface. The combined chemical vapor modification and contra-diffusion method resulted in controlled formation of a thin, defect-free, and robust ZIF-8 layer on one side of the support in aqueous solution at room temperature. The ZIF-8 membrane exhibited propylene permeance of 1.50 * 10(-8) mol m(-2) s(-1) Pa(-1) and excellent selective permeation properties; after post heat-treatment, the membrane showed ideal selectivities of C3H6/C3H8 and H2/C3H8 as high as 27.8 and 2259, respectively. The new synthesis approach holds promise for further development of the fabrication of high-quality polymer-supported ZIF membranes for practical separation applications. PMID- 26886287 TI - Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity. AB - This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs). PMID- 26886289 TI - Explaining the gender difference in self-rated health among university students in Egypt. AB - In this study the authors assessed gender differences in the relationships between self-rated health (SRH) and demographic factors, physical health, health service use, infections, a variety of symptoms and health conditions, and wider well-being features. A self-administered questionnaire was administered to 3,271 students at Assiut University, Egypt during 2009-2010. Multiple logistic regression was used (with excellent/very good SRH as dependent variable) to assess the variables that might explain the gender difference in SRH. Females had more symptoms, infectious diseases/illness periods, substantially lower quality of life, and more burdens, although their health awareness and satisfaction with social support were higher than males. The unadjusted odds ratio (OR) suggested that females were less likely than males to rate their SRH as excellent/very good [OR 0.56, 95% confidence interval (CI) 0.47-0.68]. Adjusting only for relevant physical health and health service use variables, the OR for excellent/very good SRH for females increased, but nevertheless still remained significantly lower than that of males. With further adjustment for physical health, health service use, and also for wider well-being variables, the gender difference in SRH became no longer statistically significant. Poorer physical health indicators and a lower level of wider well-being features explained the lower SRH among female Egyptian university students. Health promotion and prevention programs should consider these factors in attempting to address gender health disparities. PMID- 26886292 TI - Probing the Noninnocent pi-Bonding Influence of N-Carboxyamidoquinolate Ligands on the Light Harvesting and Redox Properties of Ruthenium Polypyridyl Complexes. AB - Electronic and photophysical characterization is presented for a series of bis heteroleptic [Ru(bpy)2(R-CAQN)](+) complexes where CAQN is a bidentate N (carboxyaryl)amidoquinolate ligand and the aryl substituent R = p-tolyl, p fluorobenzene, p-trifluoromethylbenzene, 3,5-bis(trifluoromethyl)benzene, or 4 methoxy-2,3,5,6-tetrafluorobenzene. Characterized by a strong noninnocent Ru(dpi) CAQN(pi) bonding interaction, density functional theory (DFT) analysis is used to estimate the contribution of both atomic Ru(dpi) and ligand CAQN(pi) manifolds to the frontier molecular orbitals of these complexes. UV-vis absorption and emission studies are presented where the noninnocent Ru(dpi)-CAQN(pi) bonding scheme plays a major role in defining complex electronic and photophysical properties. Oxidation potentials are tuned over a range of 0.92 V with respect to the [Ru(bpy)3](2+) reference system, hereafter referred to as 1(2+), by varying the degree of R-CAQN fluorination while maintaining consistently strong and panchromatic visible absorption properties. Electron paramagnetic resonance (EPR) spectroscopy is employed to experimentally map delocalization of the unpaired electron/electron-hole within the delocalized Ru(dpi)-CAQN(pi) singly occupied valence molecular orbital of the one-electron oxidized complexes. EPR data is complemented experimentally by UV-vis-NIR spectroelectrochemistry, and computationally by molecular orbital Mulliken contributions and spin-density analysis. It is ultimately demonstrated that the CAQN ligand framework provides a simple yet broad synthetic platform in the design of redox-active transition metal chromophores with a range of electronic and spectroscopic characteristics hinting at the diversity and potential of these complexes toward photochemical and catalytic applications. PMID- 26886290 TI - Synthesis of 9-Substituted Triptycene Building Blocks for Solid-Phase Diversification and Nucleic Acid Junction Targeting. AB - Triptycenes have been shown to bind nucleic acid three-way junctions, but rapid and efficient methods to diversify the triptycene core are lacking. An efficient synthesis of a 9-substituted triptycene scaffold is reported that can be used as a building block for solid-phase peptide synthesis and rapid diversification. The triptycene building block was diversified to produce a new class of tripeptide triptycenes, and their binding abilities toward d(CAG).(CTG) repeat junctions were investigated. PMID- 26886293 TI - Endoscopic Strip Craniectomy for Craniosynostosis: Do We Really Understand the Indications, Outcomes, and Risks? AB - Endoscopic strip craniectomy with postoperative helmet therapy has been introduced as a means to correct various forms of craniosynostosis. Although some authors have deemed the procedure safe and effective, many questions remain regarding this promising yet developing approach. The authors discuss 4 cases where patients were inadequately treated with endoscopic strip craniectomy resulting in a recommendation of complete secondary open cranial vault reconstruction. In addition, the authors present the findings from an informal survey of craniofacial colleagues to highlight an important discrepancy between published and anecdotal reports of complications. Finally, the authors highlight the need for further investigation into the proper indications and clinical outcomes of endoscopic strip craniectomy to better understand the role of this technique in the treatment of craniosynostosis. PMID- 26886294 TI - The Potential Significance of Concha Bullosa During Nasotracheal Intubation. AB - The authors experienced a case of severe epistaxis caused by accidental partial middle turbinectomy during nasotracheal intubation, which the patient had bilateral concha bullosa narrowing the nasal airway. Although anesthesiologist checked nasal airway through subjective symptoms and the size of both nostrils, they tend to overlook common anatomic variation, concha bullosa, and can injure turbinate structures. Therefore, preoperative computed tomography images should be carefully evaluated for the possibility of concha bullosa, which narrows nasal airway and induces the traumatic injury or epistaxis during nasotracheal intubation. PMID- 26886295 TI - Computed Tomography Imaging Measurement for Safer Cavernous Sinus Biopsy. AB - The aim of this study was to measure the relative location between foramen ovale and internal carotid artery. The results can guide surgeons to avoid damaging internal carotid artery in cavernous sinus biopsy. One hundred twenty people (73 men and 47 women) were involved in this study anonymously. Five parameters of both sides were measured on 2 planes. This study provides data for safer cavernous sinus biopsy. PMID- 26886296 TI - Unifying Evaluation of the Technical Performances of Iron-Tetra-amido Macrocyclic Ligand Oxidation Catalysts. AB - The main features of iron-tetra-amido macrocyclic ligand complex (a sub-branch of TAML) catalysis of peroxide oxidations are rationalized by a two-step mechanism: Fe(III) + H2O2 -> Active catalyst (Ac) (kI), and Ac + Substrate (S) -> Fe(III) + Product (kII). TAML activators also undergo inactivation under catalytic conditions: Ac -> Inactive catalyst (ki). The recently developed relationship, ln(S0/Sinfinity) = (kII/ki)[Fe(III)]tot, where S0 and Sinfinity are [S] at time t = 0 and infinity, respectively, gives access to ki under any conditions. Analysis of the rate constants kI, kII, and ki at the environmentally significant pH of 7 for a broad series of TAML activators has revealed a 6 orders of magnitude reactivity differential in both kII and ki and 3 orders differential in kI. Linear free energy relationships linking kII with ki and kI reveal that the reactivity toward substrates is related to the instability of the active TAML intermediates and suggest that the reactivity in all three processes derives from a common electronic origin. The reactivities of TAML activators and the horseradish peroxidase enzyme are critically compared. PMID- 26886297 TI - Photochemical Microcontact Printing by Tetrazole Chemistry. AB - We developed a simple method to pattern self-assembled monolayers of tetrazole triethoxylsilane with a variety of different molecules by photochemical microcontact printing. Under irradiation, tetrazoles form highly reactive nitrile imines, which react with alkenes, alkynes, and thiols. The covalent linkage to the surface could be unambiguously demonstrated by fluorescence microscopy, because the reaction product is fluorescent in contrast to tetrazole. The modified surfaces were further analyzed by X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), atomic force microscopy (AFM), and contact angle goniometry. Protein-repellent micropatterns, a biotin-streptavidin array, and structured polymer brushes could be fabricated with this straightforward method for surface functionalization. PMID- 26886298 TI - Strain Differences Determine the Suitability of Animal Models for Noninvasive In Vivo Beta Cell Mass Determination with Radiolabeled Exendin. AB - PURPOSE: Noninvasive beta cell mass (BCM) quantification is a crucial tool to understand diabetes development and progression. [(111)In]exendin is a promising agent for in vivo beta cell imaging, but tracer testing has been hampered by the lack of well-defined rodent models. PROCEDURES: Biodistribution and pancreatic uptake of [(111)In]exendin were compared in rats and mice. In selected models, the amount of [(111)In]exendin accumulation in the pancreas and other organs was determined using a model of alloxan-induced beta cell loss. GLP-1R expression levels were analyzed by RT-PCR and immunohistochemistry. RESULTS: Namely Brown Norway rats showed beta-cell-specific tracer accumulation and favorable pancreas to-background ratios for noninvasive BCM determination. Mice displayed receptor mediated [(111)In]exendin uptake in endocrine and exocrine pancreas, in spite of very low GLP-1R expression in exocrine tissue. CONCLUSIONS: Rats display better characteristics for in vivo BCM determination than mice and are suggested as a more adequate model for humans. PMID- 26886299 TI - Carcass Type Affects Local Scavenger Guilds More than Habitat Connectivity. AB - Scavengers and decomposers provide an important ecosystem service by removing carrion from the environment. Scavenging and decomposition are known to be temperature-dependent, but less is known about other factors that might affect carrion removal. We conducted an experiment in which we manipulated combinations of patch connectivity and carcass type, and measured responses by local scavenger guilds along with aspects of carcass depletion. We conducted twelve, 1-month trials in which five raccoon (Procyon lotor), Virginia opossum (Didelphis virginiana), and domestic rabbit (Oryctolagus spp.) carcasses (180 trials total) were monitored using remote cameras in 21 forest patches in north-central Indiana, USA. Of 143 trials with complete data, we identified fifteen species of vertebrate scavengers divided evenly among mammalian (N = 8) and avian species (N = 7). Fourteen carcasses (9.8%) were completely consumed by invertebrates, vertebrates exhibited scavenging behavior at 125 carcasses (87.4%), and four carcasses (2.8%) remained unexploited. Among vertebrates, mammals scavenged 106 carcasses, birds scavenged 88 carcasses, and mammals and birds scavenged 69 carcasses. Contrary to our expectations, carcass type affected the assemblage of local scavenger guilds more than patch connectivity. However, neither carcass type nor connectivity explained variation in temporal measures of carcass removal. Interestingly, increasing richness of local vertebrate scavenger guilds contributed moderately to rates of carrion removal (~6% per species increase in richness). We conclude that scavenger-specific differences in carrion utilization exist among carcass types and that reliable delivery of carrion removal as an ecosystem service may depend on robust vertebrate and invertebrate communities acting synergistically. PMID- 26886300 TI - Formulation of Granules for Site-Specific Delivery of an Antimicrobial Essential Oil to the Animal Intestinal Tract. AB - Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal feed has limited practicality due to their high volatility, odor, fast decomposition, and poor availability in the lower intestines. To solve these problems, we formulated trans-cinnamaldehyde (CIN) with an adsorbent powder and fatty acid via a melt-solidification technique. Core granules of an optimized composition contained up to 48% wt/wt CIN. The granules were then coated with an enteric polymer to impart site-specific release of CIN. CIN was mostly retained in simulated gastric fluid and released rapidly (>80% under 2 h) in simulated intestinal fluids. Rapid CIN autoxidation into cinnamic acid was inhibited by adding 1% vol/vol eugenol, which maintained CIN stability for at least 1 y. The granule formulation increased the antimicrobial activity of CIN against Escherichia coli K88 slightly with a minimum bactericidal concentration of 450 MUg/mL for CIN in lauric acid-based granules compared with 550-600 MUg/mL for palmitic acid-based granules and free CIN, respectively. These results encourage the potential use of encapsulated CIN for control of animal enteric pathogens by oral in-feed administration. PMID- 26886301 TI - Heat-Shock Protein 90-Targeted Nano Anticancer Therapy. AB - Suboptimal chemotherapy of anticancer drugs may be attributed to a variety of cellular mechanisms, which synergize to dodge the drug responses. Nearly 2 decades of heat-shock protein 90 (Hsp90)-targeted drug discovery has shown that the mono-therapy with Hsp90 inhibitors seems to be relatively ineffective compared with combination treatment due to several cellular dodging mechanisms. In this article, we have tried to analyze and review the Hsp90 and mammalian target of rapamycin (m-TOR)-mediated drug resistance mechanisms. By using this information we have discussed about the rationale behind use of drug combinations that includes both or any one of these inhibitors for cancer therapy. Currently, biodegradable nano vector (NV)-loaded novel drug delivery systems have shown to resolve the problems of poor bioavailability. NVs of drugs such as paclitaxel, doxorubicin, daunorubicin, and others have been successfully introduced for medicinal use. Hence, looking at the success of NVs, in this article we have also discussed the progress made in the delivery of biodegradable NV-loaded Hsp90 and m-TOR-targeted inhibitors in multiple drug combinations. We have also discussed the possible ways by which the market success of biodegradable NVs can positively impact the clinical trials of anti-Hsp90 and m-TOR combination strategy. PMID- 26886302 TI - Benzoic Acid and Chlorobenzoic Acids: Thermodynamic Study of the Pure Compounds and Binary Mixtures With Water. AB - Benzoic acid is a model compound for drug substances in pharmaceutical research. Process design requires information about thermodynamic phase behavior of benzoic acid and its mixtures with water and organic solvents. This work addresses phase equilibria that determine stability and solubility. In this work, Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to model the phase behavior of aqueous and organic solutions containing benzoic acid and chlorobenzoic acids. Absolute vapor pressures of benzoic acid and 2-, 3-, and 4 chlorobenzoic acid from literature and from our own measurements were used to determine pure-component PC-SAFT parameters. Two binary interaction parameters between water and/or benzoic acid were used to model vapor-liquid and liquid liquid equilibria of water and/or benzoic acid between 280 and 413 K. The PC-SAFT parameters and 1 binary interaction parameter were used to model aqueous solubility of the chlorobenzoic acids. Additionally, solubility of benzoic acid in organic solvents was predicted without using binary parameters. All results showed that pure-component parameters for benzoic acid and for the chlorobenzoic acids allowed for satisfying modeling phase equilibria. The modeling approach established in this work is a further step to screen solubility and to predict the whole phase region of mixtures containing pharmaceuticals. PMID- 26886304 TI - An Integrated Solution-Based Rapid Sample Preparation Procedure for the Analysis of N-Glycans From Therapeutic Monoclonal Antibodies. AB - Consistent glycosylation in therapeutic monoclonal antibodies is a major concern in the biopharmaceutical industry as it impacts the drug's safety and efficacy and manufacturing processes. Large numbers of samples are created for the analysis of glycans during various stages of recombinant proteins drug development. Profiling and quantifying protein N-glycosylation is important but extremely challenging due to its microheterogeneity and more importantly the limitations of existing time-consuming sample preparation methods. Thus, a quantitative method with fast sample preparation is crucial for understanding, controlling, and modifying the glycoform variance in therapeutic monoclonal antibody development. Presented here is a rapid and highly quantitative method for the analysis of N-glycans from monoclonal antibodies. The method comprises a simple and fast solution-based sample preparation method that uses nontoxic reducing reagents for direct labeling of N-glycans. The complete work flow for the preparation of fluorescently labeled N-glycans takes a total of 3 h with less than 30 min needed for the release of N-glycans from monoclonal antibody samples. PMID- 26886303 TI - Holographic Characterization of Protein Aggregates. AB - We demonstrate how holographic video microscopy can be used to detect, count, and characterize individual micrometer-scale protein aggregates as they flow down a microfluidic channel in their native buffer. Holographic characterization directly measures the radius and refractive index of subvisible protein aggregates and offers insights into their morphologies. The measurement proceeds fast enough to build up population averages for time-resolved studies and lends itself to tracking trends in protein aggregation arising from changing environmental factors. Information on individual particle's refractive indexes can be used to differentiate protein aggregates from such contaminants as silicone droplets. These capabilities are demonstrated through measurements on samples of bovine pancreas insulin aggregated through centrifugation and of bovine serum albumin aggregated by complexation with a polyelectrolyte. Differentiation is demonstrated with samples that have been spiked with separately characterized silicone spheres. Holographic characterization measurements are compared with results obtained with microflow imaging and dynamic light scattering. PMID- 26886305 TI - Pharmaceutical Applications of Relaxation Filter-Selective Signal Excitation Methods for 19F Solid-State Nuclear Magnetic Resonance: Case Study With Atorvastatin in Dosage Formulation. AB - We recently developed several new relaxation filter-selective signal excitation (RFS) methods for (13)C solid-state nuclear magnetic resonance (NMR) that allow (13)C signal extraction of the target components from pharmaceuticals. These methods were successful in not only qualification but also quantitation over the wide range of 5% to 100%. Here, we aimed to improve the sensitivity of these methods and initially applied them to (19)F solid-state NMR, on the basis that the fluorine atom is one of the most sensitive NMR-active nuclei. For testing, we selected atorvastatin calcium (ATC), an antilipid BCS class II drug that inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase and is marketed in crystalline and amorphous forms. Tablets were obtained from 2 generic drug suppliers, and the ATC content occurred mainly as an amorphous form. Using the RFS method with (19)F solid-state NMR, we succeeded in qualifying trace amounts (less than 0.5% w/w level) of crystalline phase (Form I) of ATC in the tablets. RFS methods with (19)F solid-state NMR are practical and time efficient and can contribute not only to the study of pharmaceutical drugs, including those with small amounts of a highly potent active ingredient within a formulated product, but also to the study of fluoropolymers in material sciences. PMID- 26886306 TI - Development of Suberin Fatty Acids and Chloramphenicol-Loaded Antimicrobial Electrospun Nanofibrous Mats Intended for Wound Therapy. AB - Suberin fatty acids (SFAs) isolated from outer birch bark were investigated as an antimicrobial agent and biomaterial in nanofibrous mats intended for wound treatment. Electrospinning (ES) was used in preparing the composite nonwoven nanomats containing chloramphenicol (CAM; as a primary antimicrobial drug), SFAs, and polyvinylpyrrolidone (as a carrier polymer for ES). The X-ray powder diffraction, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and texture analysis were used for the physicochemical and mechanical characterization of the nanomats. ES produced nanofibrous mats with uniform structure and with an average fiber diameter ranging from 370 to 425 nm. Microcrystalline SFAs and crystalline CAM were found to undergo a solid-state transformation during ES processing. The ES process caused also the loss of CAM in the final nanofibers. In the texture analysis, the SFAs containing nanofibers exhibited significantly higher maximum detachment force to an isolated pig skin (p < 0.05) than that obtained with the reference nanofibers. CAM exists in an amorphous form in the nanofibers which needs to be taken into account in controlling the physical storage stability. In conclusion, homogeneous composite nanofibrous mats for wound healing can be electrospun from the ternary mixture(s) of CAM, SFAs, and polyvinylpyrrolidone. PMID- 26886307 TI - Extraction Method Plays Critical Role in Antibacterial Activity of Propolis Loaded Hydrogels. AB - Extracted propolis has been used for a long time as a remedy. However, if the release rate of propolis is not controlled, the efficacy is reduced. To overcome this issue, extracted propolis was added to a cryogel system. Propolis collected from southern Brazil was extracted using different methods and loaded at different concentrations into polyvinyl alcohol (PVA) and polyacrylic acid hydrogels as carrier systems. The material properties were investigated with a focus on the propolis release profiles and the cryogel antibacterial properties against 4 different bacteria, namely: Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Pseudomonas putida. Swelling studies indicated that the swelling of the hydrogel was inversely related to propolis content. In addition, propolis release studies indicated a decreased release rate with increased propolis loading. PVA and PVA/polyacrylic acid-loaded propolis were effective against all 4 bacteria studied. These results indicate that the efficacy of propolis can be enhanced by incorporation into hydrogel carrier systems and that hydrogels with higher concentrations of propolis can be considered for use as bactericide dressing. PMID- 26886308 TI - Preparation and Physical Characterization of a Diclofenac-Ranitidine Co precipitate for Improving the Dissolution of Diclofenac. AB - Mixing aqueous solutions of sodium diclofenac (DIC-Na) and ranitidine hydrochloride (RAN.HCl) afforded an off-white solid (DIC-RAN) that was investigated from the microscopic, thermal, diffractometric, spectroscopic, and functional (chemometrics-assisted dissolution) points of view. The solid has a 2:1 (DIC:RAN) molar ratio according to (1)H nuclear magnetic resonance spectroscopy. It is thermally stable, displaying a broad endothermic signal centered at 105 degrees C in the thermogram, and its characteristic reflections in the powder X-ray diffractogram remained unchanged after a 3-month aging period. Scanning electron microscopy micrographs uncovered its morphology, whereas the spectral data suggested an interaction between the carboxylic acid of DIC and the alkyldimethylamino moiety of RAN. The dissolution of DIC-RAN was monitored at different pH values by an ultraviolet/chemometrics procedure, being complete within 5 min at pH 6.8. This compares favorably with the dissolution of a DIC-Na sample of the same particle size. PMID- 26886309 TI - Bad Science: Cause and Consequence. AB - Scientific progress is dependent on accumulation of quality data with appropriate data analysis. Unfortunately, there are a troubling number of accounts describing an inability to replicate published work. Some explanations are lack of access to proprietary reagents and equipment, or lack of expertise and know how. However, it is clear that there are many publications that are fatally flawed, and it is difficult to ascertain which ones they are, but there are clues. Many articles are improperly controlled, resulting in false-positive or -negative results. Reagents and procedures are used without verifying their specificity. There is also confirmation bias, a tendency to seek and find conclusions that we like, which is exacerbated by faithful acceptance by readers of the publication record without assessment of merit. These and other issues have slowed progress, resulted in waste of scarce funds, and even put patients at risk when clinical decisions are made according to flawed data. Solving these and related problems requires recognition of the problem and better training. We also need to take personal responsibility for not only our own work, but also for the accuracy of information in the scientific domain. PMID- 26886310 TI - The Effect of Genetic Polymorphism on the Inhibition of Azole Antifungal Agents Against CYP2C9-Mediated Metabolism. AB - We investigated the effect of cytochrome P450 (CYP) 2C9 polymorphism on the inhibition of methylhydroxylation activity of tolbutamide, a typical CYP2C9 substrate, by triazole antifungal agents, fluconazole and voriconazole. Although the Michaelis constants (Km), maximal velocities (Vmax), and Vmax/Km values for CYP2C9.1 (wild type) and CYP2C9.2 (Arg144Cys) were similar and CYP2C9.3 (Ile359Leu) had a higher Km and a lower Vmax than CYP2C9.1 and CYP2C9.2, the inhibition constants of fluconazole and voriconazole against CYP2C9.2 were lower than that against CYP2C9.1 and CYP2C9.3. These results suggest that more careful administration of azole antifungals to patients with the CYP2C9*2 allele might be required because of the strong inhibitory effects. PMID- 26886311 TI - Improved Comparative Signature Diagrams to Evaluate Similarity of Storage Stability Profiles of Different IgG1 mAbs. AB - For therapeutic protein analytical studies related to evaluating lot-to-lot variability, different processes and/or formulations, or biosimilars, there is growing interest in applying novel data visualization tools for fingerprint analysis to identify statistically significant differences between 2 samples. Comparative Signature Diagrams (CSDs) were previously developed to display such differences as colored contour plots using a variety of biophysical data sets. In this study, several improvements are proposed to enhance readability and quantitative determinations of CSDs using protein stability data from more commonly used analytical methods such as size exclusion chromatography and capillary isoelectric focusing. To demonstrate the effectiveness of improved CSDs for data visualization, an accelerated and real-time stability study was set up for an IgG1 mAb (mAb A) and its corresponding triple mutant (mAb E). The stability profiles of both mAbs were compared for differences in aggregation (size exclusion chromatography) and charge heterogeneity (capillary isoelectric focusing) profiles over time. Both traditional data analysis and the improved CSDs conclude that the triple mutant mAb E is more susceptible to physicochemical degradation than mAb A under accelerated conditions. The current abilities and limitations of CSDs to provide fingerprint analysis of protein stability profiles to facilitate the determination of similarity versus nonsimilarity between samples is discussed. PMID- 26886312 TI - Rediscovery and Revival of Analytical Refractometry for Protein Determination: Recombining Simplicity With Accuracy in the Digital Era. AB - Among "vintage" methods of protein determination, quantitative analytical refractometry has received far less attention than well-established pharmacopoeial techniques based on protein nitrogen content, such as Dumas combustion (1831) and Kjeldahl digestion (1883). Protein determination by quantitative refractometry dates back to 1903 and has been extensively investigated and characterized in the following 30 years, but has since vanished into a few niche applications that may not require the degree of accuracy and precision essential for pharmaceutical analysis. However, because high-resolution and precision digital refractometers have replaced manual instruments, reducing time and resource consumption, the method appears particularly attractive from an economic, ergonomic, and environmental viewpoint. The sample solution can be measured without dilution or other preparation procedures than the separation of the protein-free matrix by ultrafiltration, which might even be omitted for a constant matrix and excipient composition. PMID- 26886313 TI - Solution and Solid State Nuclear Magnetic Resonance Spectroscopic Characterization of Efavirenz. AB - Samples of efavirenz (EFZ) were evaluated to investigate the influence of the micronization process on EFZ stability. A combination of X-ray diffraction, thermal analysis, FTIR, observations of isotropic chemical shifts of (1)H in distinct solvents, their temperature dependence and spin-lattice relaxation time constants (T1), solution (1D and 2D) (13)C nuclear magnetic resonance (NMR), and solid-state (13)C NMR (CPMAS NMR) provides valuable structural information and structural elucidation of micronized EFZ and heptane-recrystallized polymorphs (EFZ/HEPT). This study revealed that the micronization process did not affect the EFZ crystalline structure. It was observed that the structure of EFZ/HEPT is in the same form as that obtained from ethyl acetate/hexane, as shown in the literature. A comparison of the solid-state NMR spectra revealed discrepancies regarding the assignments of some carbons published in the literature that have been resolved. PMID- 26886314 TI - Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs. AB - Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed. PMID- 26886315 TI - Does the Digestibility of Cyclodextrins Influence the In Vivo Absorption of Benzo[a]pyrene in Rats? AB - An important excipient used to overcome poor solubility is cyclodextrin. However, data in the literature suggest that excessive overdosing of cyclodextrins can decrease the absorption of compounds administered with cyclodextrins, due to their lack of release from the complex. gamma-Cyclodextrin is digestible in contrast to beta-cyclodextrins. This could potentially limit the sensitivity toward overdose, which was evaluated using benzo[a]pyrene in this study, in which rats were administered benzo[a]pyrene and different doses of the 2 cyclodextrins. Both cyclodextrins lowered the area under the curve and therefore the absorption of benzo[a]pyrene by up to a factor of 2 when dosed in high concentrations, thus indicating that overdosing of cyclodextrins may limit the oral absorption of a compound. This limitation may be artificial because the molar ratio of benzo[a]pyrene:cyclodextrin was >1:50,000 at the concentration where a significant decrease in the absorption was observed. No difference was observed between the 2 cyclodextrins, so digestibility seemed less important. More interesting was that the decrease in absorption was relatively small when compared with literature values, suggesting that the effect of overdosing a compound with cyclodextrins was lower than anticipated. PMID- 26886316 TI - Amorphous Solid Dispersions or Prodrugs: Complementary Strategies to Increase Drug Absorption. AB - Maximizing oral bioavailability of drug candidates represents a challenge in the pharmaceutical industry. In recent years, there has been an increase in the use of amorphous solid dispersions (ASDs) to address this issue, where a growing number of solid dispersion formulations have been introduced to the market. However, an increase in solubility or dissolution rate through ASD does not always result in sufficient improvement of oral absorption because solubility limitations may still exist at high doses. Chemical modification in the form of a prodrug may offer an alternative approach for these cases. Although prodrugs have been primarily used to improve membrane permeability, examples are available in which prodrugs have been used to increase drug solubility beyond what can be achieved via formulation approaches. In this mini review, the role of ASDs and prodrugs as 2 complementary approaches in improving oral bioavailability of drug candidates is discussed. We discuss the fundamental principles of absorption and bioavailability, and review available literature on both solid dispersions and prodrugs, providing a summary of their use and examples of successful applications, and cover some of the biopharmaceutics evaluation aspects for these approaches. PMID- 26886317 TI - Physiologically Based Absorption Modeling to Impact Biopharmaceutics and Formulation Strategies in Drug Development-Industry Case Studies. AB - In recent years, there has been a significant increase in use of physiologically based pharmacokinetic models in drug development and regulatory applications. Although most of the published examples have focused on aspects such as first-in human (FIH) dose predictions or drug-drug interactions, several publications have highlighted the application of these models in the biopharmaceutics field and their use to inform formulation development. In this report, we present 5 case studies of use of such models in this biopharmaceutics/formulation space across different pharmaceutical companies. The case studies cover different aspects of biopharmaceutics or formulation questions including (1) prediction of absorption prior to FIH studies; (2) optimization of formulation and dissolution method post FIH data; (3) early exploration of a modified-release formulation; (4) addressing bridging questions for late-stage formulation changes; and (5) prediction of pharmacokinetics in the fed state for a Biopharmaceutics Classification System class I drug with fasted state data. The discussion of the case studies focuses on how such models can facilitate decisions and biopharmaceutic understanding of drug candidates and the opportunities for increased use and acceptance of such models in drug development and regulatory interactions. PMID- 26886318 TI - Investigation of the Efficacy of Transdermal Penetration Enhancers Through the Use of Human Skin and a Skin Mimic Artificial Membrane. AB - The aim of this study was to investigate the behavior of promising penetration enhancers through the use of 2 different skin test systems. Hydrogel-based transdermal formulations were developed with ibuprofen as a nonsteroidal anti inflammatory drug. Transcutol and sucrose esters were used as biocompatible penetration enhancers. The permeability measurements were performed with ex vivo Franz diffusion cell methods and a newly developed Skin Parallel Artificial Membrane Permeability Assays (PAMPA) model. Franz diffusion measurement is commonly used as a research tool in studies of diffusion through synthetic membranes in vitro or penetration through ex vivo human skin, whereas Skin PAMPA involves recently published artificial membrane-based technology for the fast prediction of skin penetration. It is a 96-well plate-based model with optimized artificial membrane structure containing free fatty acid, cholesterol, and synthetic ceramide analog compounds to mimic the stratum corneum barrier function. Transdermal preparations containing 2.64% of different sucrose esters and/or Transcutol and a constant (5%) of ibuprofen were investigated to determine the effects of these penetration enhancers. The study demonstrated the good correlation of the permeability data obtained through use of human skin membrane and the in vitro Skin PAMPA system. The Skin PAMPA artificial membrane serves as quick and relatively deep tool in the early stages of transdermal delivery systems, through which the enhancing efficacy of excipients can be screened so as to facilitate the choice of effective penetration components. PMID- 26886319 TI - On the Variation of Water Diffusion Coefficient in Stratum Corneum With Water Content. AB - Water permeability and transient water sorption data in human and porcine stratum corneum (SC) are analyzed in conjunction with equilibrium water sorption data and a dynamic skin swelling model to develop a quantitative model for water diffusivity in the SC as a function of its water content. The recommended function (model 1) is phenomenological and treats the SC as a uniform, swellable slab. This approach yields satisfactory agreement with experimental data over a wide range of RH and associated equilibrium SC water content, Cw. It is supported by two alternative approaches. Model 2 considers the SC to be a multilaminate membrane consisting of alternating lipid and protein layers. Diffusivity in the protein phase is estimated from water diffusivity in other keratinized tissues, whereas diffusivity in the lipid phase is assumed to be linearly related to the swelling strain on intercellular lipids. Model 3 uses an analysis previously suggested by Stockdale to rationalize transepidermal water loss data in humans over a wide range of relative humidity. All models yield similar results for 0.20 <= Cw <= 0.78 g/cm(3), the usual range of SC water content in vivo. PMID- 26886320 TI - Systematic Evaluation of Wajima Superposition (Steady-State Concentration to Mean Residence Time) in the Estimation of Human Intravenous Pharmacokinetic Profile. AB - We present a systematic evaluation of the Wajima superpositioning method to estimate the human intravenous (i.v.) pharmacokinetic (PK) profile based on a set of 54 marketed drugs with diverse structure and range of physicochemical properties. We illustrate the use of average of "best methods" for the prediction of clearance (CL) and volume of distribution at steady state (VDss) as described in our earlier work (Lombardo F, Waters NJ, Argikar UA, et al. J Clin Pharmacol. 2013;53(2):178-191; Lombardo F, Waters NJ, Argikar UA, et al. J Clin Pharmacol. 2013;53(2):167-177). These methods provided much more accurate prediction of human PK parameters, yielding 88% and 70% of the prediction within 2-fold error for VDss and CL, respectively. The prediction of human i.v. profile using Wajima superpositioning of rat, dog, and monkey time-concentration profiles was tested against the observed human i.v. PK using fold error statistics. The results showed that 63% of the compounds yielded a geometric mean of fold error below 2 fold, and an additional 19% yielded a geometric mean of fold error between 2- and 3-fold, leaving only 18% of the compounds with a relatively poor prediction. Our results showed that good superposition was observed in any case, demonstrating the predictive value of the Wajima approach, and that the cause of poor prediction of human i.v. profile was mainly due to the poorly predicted CL value, while VDss prediction had a minor impact on the accuracy of human i.v. profile prediction. PMID- 26886321 TI - The Sustainable Release of Vancomycin and Its Degradation Products From Nanostructured Collagen/Hydroxyapatite Composite Layers. AB - Infections of the musculoskeletal system present a serious problem with regard to the field of orthopedic and trauma medicine. The aim of the experiment described in this study was to develop a resorbable nanostructured composite layer with the controlled elution of antibiotics. The layer is composed of collagen, hydroxyapatite nanoparticles, and vancomycin hydrochloride (10 wt%). The stability of the collagen was enhanced by means of cross-linking. Four cross linking agents were studied, namely an ethanol solution, a phosphate buffer solution of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride/N hydroxysuccinimide, genipin, and nordihydroguaiaretic acid. High performance liquid chromatography was used so as to characterize the in vitro release rates of the vancomycin and its crystalline degradation antibiotically inactive products over a 21-day period. The maximum concentration of the released active form of vancomycin (approximately 265 mg/L) exceeded the minimum inhibitory concentration up to an order of 17 times without triggering the burst releasing effect. At the end of the experiment, the minimum inhibitory concentration was exceeded by up to 6 times (approximately 100 mg/L). It was determined that the modification of collagen with hydroxyapatite nanoparticles does not negatively influence the sustainable release of vancomycin. The balance of vancomycin and its degradation products was observed after 14 days of incubation. PMID- 26886322 TI - Development of pH-Independent Drug Release Formulation Using Lipocalin-Type Prostaglandin D Synthase. AB - The purpose of this study was to develop a pH-independent drug release formulation using lipocalin-type prostaglandin D synthase, a member of the lipocalin superfamily, with the function of forming complexes together with various small lipophilic molecules. Dipyridamole, a poorly water-soluble drug, showing a pH-dependent solubility profile, was used as the model drug. The solubilization of dipyridamole was achieved by a simple complex formulation method with lipocalin-type prostaglandin D synthase. The complex formulation was produced successfully by spray drying, and the obtained powder formulation showed complete dissolution in fasted-state simulated gastric fluid (pH, 1.6) and phosphate-buffered solution (pH, 6.8). In addition, the potential stability of the complex formulation was assessed, and the dissolution profile of the produced powder at pH 6.8 was maintained after 4-week storage under several storage conditions. Furthermore, a pharmacokinetic study using hypochlorhydria model rats was performed to verify the improvement of the intestinal absorption behavior, and eventually the complex formulation overcame the problematic absorption profile of dipyridamole in the elevated gastric pH conditions. These results, taken together, demonstrate that the use of this well-designed drug-delivery carrier is feasible for the development of pH-independent drug release formulations. PMID- 26886323 TI - Application of Cassette Ultracentrifugation Using Non-labeled Compounds and Liquid Chromatography-Tandem Mass Spectrometry Analysis for High-Throughput Protein Binding Determination. AB - Membrane-based devices typically used for serum protein binding determination are not fully applicable to highly lipophilic compounds because of nonspecific binding to the device membrane. Ultracentrifugation, however, completely eliminates the issue by using a membrane-free approach, although its wide application has been limited. This lack of utilization is mainly attributed to 2 factors: the high cost in acquiring and handling of radiolabeled compounds and low assay throughput owing to the difficulties in process automation. To overcome these challenges, we report a high-throughput workflow by cassette ultracentrifugation of nonradiolabeled compounds followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Twenty compounds with diverse physicochemical and protein binding properties were selected for the evaluation of the workflow. To streamline the working process, approaches of matrix balancing for all the samples for LC-MS/MS analysis and determining free fraction without analytical calibration curves were adopted. Both the discrete ultracentrifugation of individual compounds and cassette ultracentrifugation of all the test compounds followed by simultaneous LC-MS/MS analysis exhibited a linear correlation with literature values, demonstrating respectively the validity of the ultracentrifugation process and the cassette approach. The cassette ultracentrifugation using nonradiolabeled compounds followed by LC-MS/MS analysis has greatly facilitated its application for high-throughput protein binding screening in drug discovery. PMID- 26886324 TI - Subvisible Particle Content, Formulation, and Dose of an Erythropoietin Peptide Mimetic Product Are Associated With Severe Adverse Postmarketing Events. AB - Peginesatide (Omontys((r)); Affymax, Inc., Cupertino, CA) was voluntarily withdrawn from the market less than a year after the product launch. Although clinical trials had demonstrated the drug to be safe and efficacious, 49 cases of anaphylaxis, including 7 fatalities, were reported not long after market introduction. Commercialization was initiated with a multiuse vial presentation, which differs in formulation from the single-use vial presentation used in phase 3 studies. Standard physical and chemical testing did not indicate any deviation from product specifications in either formulation. However, an analysis of subvisible particulates using nanoparticle tracking analysis and flow imaging revealed a significantly higher concentration of subvisible particles in the multiuse vial presentation linked to the hypersensitivity cases. Although it is unknown whether the elevated particulate content is causally related to these serious adverse events, this report illustrates the utility of characterizing subvisible particulates not captured by conventional light obscuration. PMID- 26886325 TI - Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective. AB - The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science. PMID- 26886326 TI - An Injectable Gel Platform for the Prolonged Therapeutic Effect of Pitavastatin in the Management of Hyperlipidemia. AB - In this study, an injectable in situ-forming gel has been designed and fabricated for the controlled and prolonged release of pitavastatin calcium (Pit) for treating hyperlipidemia. By mixing phospholipids and soybean oil with ethanol, the phospholipid-based platform material (PSE) displayed in a sol state with low viscosity in vitro. After subcutaneous injection, pregel solution underwent rapid phase separation and gelation in situ thus forming a drug release depot. Pit was loaded within PSE (PSE-P), which achieved prolonged release profiles for 15 consecutive days in vitro. Correspondingly, the pharmacokinetic study in rats demonstrated that PSE-P achieved sustained in vivo release for 15 days after 1 subcutaneous injection. The pharmacodynamic study in hyperlipidemia rats further revealed that the levels of total cholesterol, total triglyceride, and low density lipoprotein decreased remarkably, and the in vivo therapeutic effect was well maintained for over 20 days. Additionally, PSE-P showed mild tissue inflammatory responses and excellent degradability in vivo. Thus, in situ-forming PSE-P gel represents a viable and promising drug delivery platform to achieve long-term therapeutic effects in the management of hyperlipidemia. PMID- 26886327 TI - Do We Bury Antibacterials When Launching? Cefaclor Example. AB - This study aimed to compare existing dosing regimens of cefaclor with recommended pharmacokinetic/pharmacodynamic (PK/PD) parameters and to see if the proposed dosing regimen could have been the reason for development of bacterial resistance. PKs of cefaclor were determined after administrating the highest therapeutic dose of 750 mg in standard release (SF) and modified release form (MRF) in 12 volunteers. The study was performed on clinical isolates of the most frequent causative agents in urinary and respiratory infections. Minimum inhibitory concentration (MIC), postantibiotic effect, and PK/PD efficacy indices were determined. Peak plasma concentrations of 23.142 +/- 5.67 (SF) and 8.7 +/- 2.09 MUg/mL (MRF) were observed after 40-60 min and 3.04 +/- 0.75 h, respectively. MIC for investigated bacterial strains ranged from 1 to 4 mg/L. Postantibiotic effect lasted from 2.10-2.18 +/- 0.2 h for Gram-positive to 0.58 0.90 +/- 0.05 h for Gram-negative bacteria. PK/PD indices (t > MIC) ranged from 27.08 +/- 5.93% to 43.23 +/- 6.54% of 8-h dosing interval (SF) and 22.57 +/- 8.93% to 49.65 +/- 1.95% of 12-h dosing interval (MRF). Plasma levels were below MIC for more than 50% of the dosing interval even for the most sensitive pathogens (MIC = 1 mg/L). During both dosing intervals the total "antibacterial activity" was not longer than 6 h for Gram-positive and 5 h for Gram-negative bacteria for SF and 9 h for Gram-positive and 5 h for Gram-negative bacteria for MRF. PMID- 26886328 TI - Clarifications: Dermal Clearance Model for Epidermal Bioavailability Calculations. AB - Delivery through the skin, either through topical application for therapeutic or cosmetic benefits or intradermal delivery through emerging technologies such as microneedles, has been studied extensively in past decades. In a previous report in this journal one of the authors proposed an extensive model for predicting dermal clearance under pseudo steady-state conditions from the physiochemical properties of the compound (Ibrahim et al. 2012 J Pharm Sci, 101:2094-2108). This note provides some clarifications regarding this model, highlighting critical points that must be considered when using the model. The points are discussed in the order of relevance and complement the understanding of how molecules delivered intradermally clear from the dermis into the systemic circulation. In brief, solute binding to protein is reconsidered, limitations in using empirical models to determine physiochemical properties of a molecule are highlighted, and readers are informed about critical details regarding the calculations. PMID- 26886329 TI - Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs: Investigation Into Celecoxib Incorporation and Solubility-In Vitro Permeability Enhancement. AB - Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase in CXB solubility leads to a subsequent increase in permeability across intestinal barrier and (2) the presence of bile salts affects the solubility and permeability behavior of CXB formulations. By formulating CXB solid phospholipid (PL) dispersions with various PL-to-drug ratios using freeze drying, the present study illustrated that the enhancement of CXB solubility was not proportionally translated into enhanced permeability; both parameters were highly dependent on the PL-to-drug ratios as well as the dispersion media (i.e., the presence of 3-mM sodium taurocholate). This study highlights the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed. PMID- 26886331 TI - Proton-Coupled Organic Cation Antiporter Contributes to the Hepatic Uptake of Matrine. AB - Matrine is the major bioactive alkaloid found in certain Sophora plants and has been used for the treatment of liver diseases and protection of liver function. The aim of this study was to investigate the human liver uptake mechanism of matrine by using HepG2 cells as the in vitro model. Matrine was transported into HepG2 cells in a time- and temperature-dependent manner. The cellular uptake was saturable and was significantly reduced by the metabolic inhibitors, such as sodium azide and rotenone. Furthermore, the uptake of matrine was found to be regulated by a protonophore (carbonyl cyanide 4 (trifluoromethoxy)phenylhydrazone) and pH, indicating that this influx transporter may be a proton-coupled antiporter. The uptake of matrine was sensitive to inhibition by the cationic drugs including pyrilamine, quinidine, verapamil, amantadine, diphenhydramine, and cimetidine but insensitive to other typical substrates or inhibitors of well-known organic cation transport systems. The present study reveals that, for the first time, in HepG2 cells, the existence of a proton-coupled organic cation antiporter that contributes substantially to the hepatic uptake of matrine. PMID- 26886330 TI - Investigation of the Changes in Aerosolization Behavior Between the Jet-Milled and Spray-Dried Colistin Powders Through Surface Energy Characterization. AB - This study aimed to investigate the surface energy factors behind improved aerosolization performance of spray-dried colistin powder formulations compared with those produced by jet milling. Inhalable colistin powder formulations were produced by jet milling or spray drying (with or without l-leucine). Scanning electron micrographs showed the jet-milled particles had irregularly angular shapes, whereas the spray-dried particles were more spherical. Significantly higher fine particle fractions were measured for the spray-dried (43.8%-49.6%) versus the jet-milled formulation (28.4%) from a Rotahaler at 60 L/min; albeit the size distribution of the jet-milled powder was smaller. Surprisingly, addition of l-leucine in the spray drying feed solution gave no significant improvement in fine particle fraction. As measured by inverse gas chromatography, spray-dried formulations had significantly (p < 0.001) lower dispersive, specific, and total surface energy values and more uniform surface energy distributions than the jet-milled powder. Interestingly, no significant difference was measured in the specific and total surface energy values between the spray-dried formulation with or without l-leucine. Based on our previous findings in the self-assembling behavior of colistin in aqueous solution and the surface energy data obtained here, we propose the self-assembly of colistin molecules during spray drying contributed significantly to the reduction of surface free energy and the superior aerosolization performance. PMID- 26886332 TI - Electrospun Poly(N-isopropylacrylamide)/Ethyl Cellulose Nanofibers as Thermoresponsive Drug Delivery Systems. AB - Fibers of poly(N-isopropylacrylamide) (PNIPAAm), ethyl cellulose (EC), and a blend of both were successfully fabricated by electrospinning. Analogous drug loaded fibers were prepared loaded with ketoprofen (KET). Scanning and transmission electron microscopy showed that the fibers were largely smooth and cylindrical, with no phase separation observed. The addition of KET to the spinning solutions did not affect the morphology of resultant fibers, and no drug particles could be observed to separate from the polymer matrix. X-ray diffraction demonstrated that the drug was present in the amorphous physical form in the fiber matrix. There are significant intermolecular interactions between KET and polymers, as evidenced by IR spectroscopy and molecular modeling. Water contact angle measurements proved that the PNIPAAm and PNIPAAm/EC fibers switched from being hydrophilic to hydrophobic when the temperature was increased through the lower critical solution temperature of 32 degrees C. In vitro drug release studies found that the PNIPAAm/EC blend nanofibers were able to synergistically combine the properties of the 2 polymers, giving temperature-sensitive systems with sustained release properties. In addition, they were established to be nontoxic and suitable for cell growth. This study demonstrates that electrospun blend PNIPAAm/EC fibers comprise effective and biocompatible materials for drug delivery systems and tissue engineering. PMID- 26886333 TI - Controlled Release of Antibiotics From Vitamin E-Loaded Silicone-Hydrogel Contact Lenses. AB - Symptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE((r)) TrueEyeTM and ACUVUE OASYS((r)) contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE((r)) TrueEyeTM and ACUVUE OASYS((r)), respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5- and 10-fold, for the TrueEyeTM and OASYS((r)), respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E-loaded lenses retain all critical properties for in vivo use. PMID- 26886335 TI - Sponge-Like Dressings Based on the Association of Chitosan and Sericin for the Treatment of Chronic Skin Ulcers. II. Loading of the Hemoderivative Platelet Lysate. AB - Platelet lysate (PL) was loaded into dressings based on chitosan glutamate (CSG) low and high molecular weight, sericin (Ser), and glycine (Gly). A synergic effect of Ser and PL on fibroblast proliferation was proved in vitro. Two different PL loading approaches were considered: the first provided to prepare dressings by freeze-drying a mixture of PL and CSG/Gly/Ser solution, the second approach consisted in the extemporarily loading of PL in the CSG/Gly/Ser freeze dried dressings. As for the first approach, PL loading did not produce any variation in dressing mechanical properties. Such dressings absorbed a high amount (about 8-fold of dry weight) of phosphate-buffered saline (fluid mimicking wound exudate), forming a gel with pseudoplastic and elastic properties. Platelet derived growth factor AB assay indicated that neither freeze-drying nor the excipients alter PL growth factor content. As for the second approach, mechanical and rheological properties of the gel formed upon PL absorption enabled to choose a PL loading of about 90 MUL/cm(2). Upon contact with fibroblasts, all PL loaded formulations increased the number not only of viable cells but also of those in the proliferative phase. Histological studies effected on human skin strips pointed out the positive effect of PL loaded dressings on dermal matrix reconstruction. PMID- 26886334 TI - Development and Evaluation of Biodegradable Particles Coloaded With Antigen and the Toll-Like Receptor Agonist, Pentaerythritol Lipid A, as a Cancer Vaccine. AB - Immune adjuvants are important components of current and prospective cancer vaccines. In this study, we aimed at evaluating the use of a synthetic lipid A derivative, pentaerythritol lipid A (PET lipid A), loaded into poly(lactic-co glycolic acid) particles, as a potential cancer vaccine adjuvant. Poly(lactic-co glycolic acid) particles (size range: 250-600 nm) were successfully formulated to include PET lipid A and/or the model tumor antigen, chicken ovalbumin (OVA). It was shown that particulated PET lipid A had a distinct advantage at promoting secretion of the immune potentiating cytokine, IL-12p70, and upregulating key costimulatory surface proteins, CD86 and CD40, in murine dendritic cells in vitro. In a murine tumor model, involving prophylactic vaccination with various permutations of soluble versus particulated formulations of OVA with or without PET lipid A, modest benefit was observed in terms of OVA-specific cell-mediated immune responses when PET lipid A was delivered in particles. These findings translated into a corresponding trend toward increased survival of mice challenged with OVA-expressing tumor cells (E.G7). In terms of translation of safe adjuvants into the clinic, these results promote the concept of delivering toll-like receptor-4 agonists in particles because doing so improves their adjuvant properties, while decreasing the chances of adverse effects due to off target uptake by nonphagocytic cells. PMID- 26886337 TI - Cyclodextrin and Meglumine-Based Microemulsions as a Poorly Water-Soluble Drug Delivery System. AB - Cyclodextrins (CDs) and meglumine (MEG) are pharmaceutical excipients widely used to improve solubility of poorly water-soluble drugs. The purpose of this work was to study the effect of CDs or MEG on the internal microstructure of soya oil based O/W microemulsions (MEs) and on the modulation of the solubility and release rate of Class II model hydrophobic drugs, sulfamerazine and indomethacin. The pseudoternary phase diagrams revealed that higher proportions of oil phase, as well as the presence of beta-cyclodextrin (betaCD), methyl-betaCD, and MEG, favored the incorporation of the drugs. The conductivity studies, particle size, and zeta potential analysis showed that the O/W ME structure remained unaffected and that the ME presented reduced droplet sizes after the incorporation of the ligands. The drug-component interactions were assessed by proton nuclear magnetic resonance studies. The highest incorporations of sulfamerazine (35.6 mg/mL) and indomethacin (73.1 mg/mL) were obtained with the ME with W = 5%, MEG and W = 1.8% betaCD in a phosphate buffer solution of pH 8, respectively. In addition, the ligands in ME significantly enhanced the released amount of the drugs, probably due to a solubilizing effect that facilitates the drug to penetrate the unstirred water layer adjacent to membranes. PMID- 26886336 TI - Dynamic and Static Simulations of Fluvoxamine-Perpetrated Drug-Drug Interactions Using Multiple Cytochrome P450 Inhibition Modeling, and Determination of Perpetrator-Specific CYP Isoform Inhibition Constants and Fractional CYP Isoform Contributions to Victim Clearance. AB - Fluvoxamine-perpetrated drug-drug interactions (DDIs) of victims metabolized by multiple cytochrome P450 isoforms (CYP1A2, CYP2C19, and CYP3A4) were simulated using 2 compartment-based tube modeling, assuming a multiple inhibition-constant (Ki) model, as well as a previously reported single Ki model. Good fittings were obtained for all DDIs using consistent perpetrator-specific CYP isoform Kis and fractional CYP isoform contributions to victim clearance in concordance with literature information. Through these simulations, the following rules to predict DDI were derived. Overall enzymatic inhibitory activity calculated from static DDI data determines entirely dynamic DDIs. DDI-relevant time-dependent hepatic blood unbound perpetrator levels can be approximated to mean hepatic blood unbound perpetrator levels in any victim DDIs when a perpetrator is supplied consistently. Static and dynamic multiple CYP model-based simulations agree with one another. Fluvoxamine-perpetrated DDIs can be bridged to other perpetrator DDIs. The derived rules will allow simpler prediction of DDIs from in vivo DDI databases. Tens or hundreds of Ki gaps between in vitro and in vivo data could be reduced to within severalfold using the liver-microsome contamination model, thus suggesting that microsomes qualified with contamination would greatly improve prediction of DDIs from in vitro data. PMID- 26886338 TI - Sponge-Like Dressings Based on the Association of Chitosan and Sericin for the Treatment of Chronic Skin Ulcers. I. Design of Experiments-Assisted Development. AB - The aim of the present work was the development of sponge-like dressings based on chitosan glutamate (high molecular weight) and sericin for the treatment of chronic skin ulcers. Dressings were prepared by freeze-drying and glycine was added as cryoprotectant agent. Dressing development was assisted by design of experiments, using a simplex centroid design. Mechanical resistance, hydration propensity, viscous, and viscoelasticity properties of dressings were considered as response variables. The superimposition of the contour plots, calculated by the best fit model for each response variable, permitted to individuate a region of the factor space where the dressing of optimized quantitative composition was chosen. Such a dressing was able to absorb high amount of phosphate-buffered saline forming a gel characterized by rheological properties enabling both a lubricant and a protective effect. The optimized formulation was characterized by optimal mechanical properties and by cell proliferation and antioxidant activity on human fibroblast cell line. PMID- 26886339 TI - One-Step Self-Assembling Method to Prepare Dual-Functional Transferrin Nanoparticles for Antitumor Drug Delivery. AB - Protein-based nanoparticles hold great promise in both preclinical and clinical practices due to their high biocompatibility and biodegradability. However, the complicated preparations often denature proteins, which subsequently diminish their bioactivity. To overcome these drawbacks, we developed a one-step self assembling method for preparing protein-based nanoparticles. Transferrin (Tf), a targeting protein, was mixed with 2-mercaptoethanol to break disulfide bonds. Using this method, Tf-PTX-NPs (paclitaxel-loaded Tf nanoparticles) could be readily obtained. Tf-PTX-NPs were round and their diameter could be controlled in the range of 5-200 nm. The bioactivity of Tf to its receptor after forming nanoparticles was also confirmed in vitro. Tf-PTX-NPs also could inhibit the tumor growth to some extent in a mice tumor xenograft model. Therefore, using this self-assembling method, we fabricated this antitumor Tf-based nanoparticle, in which Tf acted as both the targeting moiety and drug carrier. PMID- 26886340 TI - Ketoconazole Stereoisomers Differentially Induce Cytochrome P450 1A1 Between Human Hepatoma HepG2 and Mouse Hepatoma Hepa1c1c7 Cells. AB - Ketoconazole (KTZ) has 2 chiral centers with the therapeutically active form being a racemic mixture of 2 cis-enantiomers, namely, (2R,4S)-(+)-KTZ and (2S,4R) (-)-KTZ. The aims of the present study were to examine the effects of (+)-KTZ, ( )-KTZ, and (+/-)-KTZ on aryl hydrocarbon receptor activation and subsequently CYP1A1 induction in both human HepG2 and murine Hepa1c1c7 hepatoma cells, and to further test their inhibitory effect using recombinant human and mouse CYP1A1 enzymes. Our results demonstrated that (+)-KTZ induced human CYP1A1 more than (-) KTZ, whereas on the other hand (-)-KTZ induced murine Cyp1a1 more than (+)-KTZ at the mRNA, and activity levels. Human CYP1A1 showed higher affinity to 7ER compared with murine Cyp1a1 (Km values 13.29 nM for human vs. 168.1 nM for murine). The intrinsic clearance values for human and murine CYP1A1 were 194.1 and 87.6 MUL/pmol P450/min, respectively, whereas, Vmax values were 2.58 and 14.73 pmol/pmol P450/min, respectively. (+)-KTZ and (-)-KTZ directly inhibited CYP1A1 activity by noncompetitive mechanism. The affinity of (-)-KTZ to interact with human CYP1A1 and murine Cyp1a1 was significantly different from (+)-KTZ, as the Ki values for human CYP1A1 and murine Cyp1a1 were 199.4 and 413.7 nM, respectively, for (+)-KTZ, and 269.3 and 230.8 nM, respectively, for (-)-KTZ. PMID- 26886341 TI - Alteration in Intrapulmonary Pharmacokinetics of Aerosolized Model Compounds Due to Disruption of the Alveolar Epithelial Barriers Following Bleomycin-Induced Pulmonary Fibrosis in Rats. AB - Idiopathic pulmonary fibrosis is a lethal lung disease that is characterized by the accumulation of extracellular matrix and a change in lung structure. In this study, intrapulmonary pharmacokinetics of aerosolized model compounds were evaluated using rats with bleomycin-induced pulmonary fibrosis. Aerosol formulations of indocyanine green, 6-carboxyfluorescein (6-CF), and fluorescein isothiocyanate dextrans (FD; 4.4, 10, 70, and 250 kDa) were administered to rat lungs using a MicroSprayer. Indocyanine green fluorescence signals were significantly weaker in fibrotic lungs than in control lungs and 6-CF and FD concentrations in the plasma of pulmonary fibrotic animals were markedly higher than in the plasma of control animals. Moreover, disrupted epithelial tight junctions, including claudins-1, -3, and -5, were observed in pulmonary fibrotic lesions using immunofluorescence microscopy. In addition, destruction of tight junctions on model alveolar epithelial cells (NCI-H441) by transforming growth factor-beta1 treatment enhanced the permeability of 6-CF and FDs through NCI-H441 cell monolayers. These results indicate that aerosolized drugs are easily distributed into the plasma after leakage through damaged tight junctions of alveolar epithelium. Therefore, the development of delivery systems for anti fibrotic agents to improve intrapulmonary pharmacokinetics may be necessary for effective idiopathic pulmonary fibrosis therapy. PMID- 26886343 TI - An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid. AB - To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers. PMID- 26886342 TI - Size and Charge Dependence of Ion Transport in Human Nail Plate. AB - The electrical properties of human nail plate are poorly characterized yet are a key determinate of the potential to treat nail diseases, such as onychomycosis, using iontophoresis. To address this deficiency, molar conductivities of 17 electrolytes comprising 12 ionic species were determined in hydrated human nail plate in vitro. Cation transport numbers across the nail for 11 of these electrolytes were determined by the electromotive force method. Effective ionic mobilities and diffusivities at infinite dilution for all ionic species were determined by regression analysis. The ratios of diffusivities in nail to those in solution were found to correlate inversely with the hydrodynamic radii of the ions according to a power law relationship having an exponent of -1.75 +/- 0.27, a substantially steeper size dependence than observed for similar experiments in skin. Effective diffusivities of cations in nail were 3-fold higher than those of comparably sized anions. These results reflect the strong size and charge selectivity of the nail plate for ionic conduction and diffusion. The analysis implies that efficient transungual iontophoretic delivery of ionized drugs having radii upward of 5 A (molecular weight, ca. >= 340 Da) will require chemical or mechanical alteration of the nail plate. PMID- 26886344 TI - Origin of Aggregate Formation in Antibody Crystal Suspensions Containing PEG. AB - The crystalline state of proteins is deemed as a promising formulation platform for biopharmaceuticals. However, a stabilizing effect of protein crystal suspensions is controversially discussed. In fact, antibodies can display an increased aggregation and particle formation profile after the crystallization process compared with liquid or solid amorphous formulations. Nevertheless, studies regarding aggregate formation and its origin remain meager in literature. It was the aim of this study to investigate these aspects for a model IgG antibody (mAb1), which shows an increased aggregate formation after crystallization with polyethylene glycol. The presence of a dynamic equilibrium, a steady exchange of protein between the crystals and the supernatant, was demonstrated by replacing the supernatant with an identical but fluorescence labeled protein solution and followed by confocal laser scanning microscopy. Aggregate formation was monitored by size exclusion high-pressure chromatography and flow cytometry. Constantly increasing aggregate levels were found for the crystal fraction and for the supernatant. For the later, markedly higher particle counts were detected. The labeled supernatant and the unlabeled protein crystals allowed a precise identification of the origin of the aggregates. The rising aggregate fractions of the crystals displayed high mean fluorescence intensities that elucidated their origin in the supernatant. PMID- 26886345 TI - Development and Evaluation of a Novel Intranasal Spray for the Delivery of Amantadine. AB - The aim of this study was to develop and characterize an intranasal delivery system for amantadine hydrochloride (AMT). Optimal formulations consisted of a thermosensitive polymer Pluronic(r) 127 and either carboxymethyl cellulose or chitosan which demonstrated gel transition at nasal cavity temperatures (34 +/- 1 degrees C). Rheologically, the loss tangent (Tan delta) confirmed a 3-stage gelation phenomena at 34 +/- 1 degrees C and non-Newtonian behavior. Storage of optimized formulation carboxymethyl cellulose and optimal formulation chitosan at 4 degrees C for 8 weeks resulted in repeatable release profiles at 34 degrees C when sampled, with a Fickian mechanism earlier on but moving toward anomalous transport by week 8. Polymers (Pluronic(r) 127, carboxymethyl cellulose, and chitosan) demonstrated no significant cellular toxicity to human nasal epithelial cells up to 4 mg/mL and up to 1 mM for AMT (IC50: 4.5 +/- 0.05 mM). Optimized formulation carboxymethyl cellulose and optimal formulation chitosan demonstrated slower release across an in vitro human nasal airway model (43%-44% vs 79 +/- 4.58% for AMT). Using a human nasal cast model, deposition into the olfactory regions (potential nose-to-brain) was demonstrated on nozzle insertion (5 mm), whereas tilting of the head forward (15 degrees ) resulted in greater deposition in the bulk of the nasal cavity. PMID- 26886346 TI - Acetate- and Citrate-Specific Ion Effects on Unfolding and Temperature-Dependent Aggregation Rates of Anti-Streptavidin IgG1. AB - Controlling and predicting unwanted degradation, such as non-native aggregation, is a long-standing challenge for mAbs and other protein-based products. mAb aggregation rates are typically sensitive to temperature, pH, and the addition of excipients. Quantitatively comparing temperature-dependent aggregation rates across multiple possible formulations is a challenge in product development. A parallel temperature initial rate method is used to efficiently and accurately determine initial rates for anti-streptavidin (AS) IgG1 aggregation as a function of pH, [NaCl], and in the presence of acetate versus citrate buffer. Parallel temperature initial rates are shown to agree with results from a traditional, isothermal method and permits direct comparison of the formulations across almost 3 orders of magnitude of aggregation rates. The apparent midpoint unfolding temperatures (through differential scanning calorimetry) and the effective activation energy values (Ea) are generally higher in acetate buffer compared with citrate buffer, which is consistent with preferential accumulation of citrate ions compared with acetate ions that was speculated in previous work (Barnett et al., J Phys Chem B, 2015). Static light scattering and Kirkwood-Buff analysis show that AS-IgG1 has stronger net repulsive protein-protein interactions in acetate compared with citrate buffer, also consistent with increased values of Ea. In an extreme case, aggregation of AS-IgG1 is effectively eliminated across all practical temperatures at pH 4 in 10 mM sodium acetate but proceeds readily in citrate buffer. PMID- 26886347 TI - Allometric Scaling of Therapeutic Monoclonal Antibodies Using Antigen Concentration as a Correction Factor: Application to the Human Clearance Prediction. AB - Allometric scaling has been widely used for predictions of human pharmacokinetic (PK) parameters in the development of monoclonal antibody (mAb) drugs, and some correction factors have been proposed to improve the estimations. However, classic correction factors fail to offer a complete explanation of the additional differences among species besides the body weight and, thus, lack enough power to further improve the predictions. In this study, the antigen concentration was initially set as a new correction factor to predict the human clearance (CL) of mAbs. Bevacizumab was intravenously injected into 2 animal species and humans to obtain PK data to predict human CL from the animal data. Additionally, a new approach was also validated with data from 3 other mAbs which were collected through a literature review of published work. Accordingly, allometric scaling with a correction factor of the antigen concentration generated accurate estimations of the human CL of 4 mAbs, which were superior to the results obtained by other classic scaling methods. More importantly, the proposed method also achieved good predictions of individual human CL of bevacizumab. In conclusion, the potential of this method as a powerful tool for human PK estimation of mAbs in species translation has been demonstrated. PMID- 26886348 TI - Preservation of Biospecimens at Ambient Temperature: Special Focus on Nucleic Acids and Opportunities for the Biobanking Community. AB - Several approaches to the preservation of biological materials at ambient temperature and the relative impact on sample stability and degradation are reviewed, with a focus on nucleic acids. This appraisal is undertaken within the framework of biobank risk, quality management systems, and accreditation, with a view to assessing how best to apply ambient temperature sample storage to ensure stability, reduce costs, improve handling logistics, and increase the efficiency of biobank procedures. PMID- 26886349 TI - Evolution of a Planktonic Foraminifer during Environmental Changes in the Tropical Oceans. AB - Ecological adaptation to environmental changes is a strong driver of evolution, enabling speciation of pelagic plankton in the open ocean without the presence of effective physical barriers to gene flow. The tropical ocean environment, which plays an important role in shaping marine biodiversity, has drastically and frequently changed since the Pliocene. Nevertheless, the evolutionary history of tropical pelagic plankton has been poorly understood, as phylogeographic investigations are still in the developing state and paleontological approaches are insufficient to obtain a sequential record from the deep-sea sediments. The planktonic foraminifer Pulleniatina obliquiloculata is widely distributed in the tropical area throughout the world's oceans, and its phylogeography is well established. It is thus one of the best candidates to examine how past environmental changes may have shifted the spatial distribution and affected the diversification of tropical pelagic plankton. Such an examination requires the divergence history of the planktonic foraminifers, yet the gene marker (partial small subunit (SSU) rDNA) previously used for phylogeographic studies was not powerful enough to achieve a high accuracy in estimating the divergence times. The present study focuses on improving the precision of divergence time estimates for the splits between sibling species (genetic types) of planktonic foraminifers by increasing the number of genes as well as the number of nucleotide bases used for molecular clock estimates. We have amplified the entire coding regions of two ribosomal RNA genes (SSU rDNA and large subunit (LSU) rDNA) of three genetic types of P. obliquiloculata and two closely related species for the first time and applied them to the Bayesian relaxed clock method. The comparison of the credible intervals of the four datasets consisting either of sequences of the partial SSU rDNA, the complete SSU rDNA, LSU rDNA, or a combination of both genes (SSU+LSU) clearly demonstrated that the two-gene dataset improved the accuracy of divergence time estimates. The P. obliquiloculata lineage diverged twice, first at the end of the Pliocene (3.1 Ma) and again in the middle Pleistocene (1.4 Ma). Both timings coincided with the environmental changes, which indirectly involved geographic separation of populations. The habitat of P. obliquiloculata was expanded toward the higher latitudinal zones during the stable warm periods and subsequently placed on the steep environmental gradients following the global cooling. Different environmental conditions in the stable warm tropics and unstable higher latitudes may have triggered ecological divergence among the populations, leading to adaptive differentiation and eventually speciation. A comprehensive analysis of divergence time estimates combined with phylogeography enabled us to reveal the evolutionary history of the pelagic plankton and to find the potential paleoenvironmental events, which could have changed their biogeography and ecology. PMID- 26886350 TI - Three Millennia of Southwestern North American Dustiness and Future Implications. AB - Two sediment records of dust deposition from Fish Lake, in southern Colorado, offer a new perspective on southwest United States (Southwest) aridity and dustiness over the last ~3000 years. Micro scanning X-ray fluorescence and grain size analysis provide separate measures of wind-deposited dust in the lake sediment. Together these new records confirm anomalous dustiness in the 19th and 20th centuries, associated with recent land disturbance, drought, and livestock grazing. Before significant anthropogenic influences, changes in drought frequency and aridity also generated atmospheric dust loading. Medieval times were associated with high levels of dustiness, coincident with widespread aridity. These records indicate the Southwest is naturally prone to dustiness. As global and regional temperatures rise and the Southwest shifts toward a more arid landscape, the Southwest will likely become dustier, driving negative impacts on snowpack and water availability, as well as human health. PMID- 26886352 TI - 1H, 13C, and 15N resonance assignments of an enzymatically active domain from the catalytic component (CDTa, residues 216-420) of a binary toxin from Clostridium difficile. AB - Clostridium difficile is a bacterial pathogen and is the most commonly reported source of nosocomial infection in industrialized nations. Symptoms of C. difficile infection (CDI) include antibiotic-associated diarrhea, pseudomembranous colitis, sepsis and death. Over the last decade, rates and severity of hospital infections in North America and Europe have increased dramatically and correlate with the emergence of a hypervirulent strain of C. difficile characterized by the presence of a binary toxin, CDT (C. difficile toxin). The binary toxin consists of an enzymatic component (CDTa) and a cellular binding component (CDTb) that together form the active binary toxin complex. CDTa harbors a pair of structurally similar but functionally distinct domains, an N terminal domain (residues 1-215; (1-215)CDTa) that interacts with CDTb and a C terminal domain (residues 216-420; (216-420)CDTa) that harbors the intact ADP ribosyltransferase (ART) active site. Reported here are the (1)H, (13)C, and (15)N backbone resonance assignments of the 23 kDa, 205 amino acid C-terminal enzymatic domain of CDTa, termed (216-420)CDTa. These NMR resonance assignments for (216-420)CDTa represent the first for a family of ART binary toxins and provide the framework for detailed characterization of the solution-state protein structure determination, dynamic studies of this domain, as well as NMR-based drug discovery efforts. PMID- 26886353 TI - The paraoxonase disruption hypothesis in sporadic ALS steamrolled. PMID- 26886355 TI - Understanding migraine and psychiatric comorbidity. AB - PURPOSE OF REVIEW: This article describes recent trends in our understanding of the role of psychiatric disorders in the experience and treatment of migraine, and the role of migraine in the experience and treatment of psychiatric disorders. RECENT FINDINGS: Although the majority of studies evaluating psychiatric comorbidity in migraine have focused on depression, anxiety, and bipolar disorders are highly associated with migraine and relevant for prognosis and treatment planning. Comorbid psychiatric disorders may be associated with poorer treatment response for some acute pharmacotherapies; however, people with comorbid migraine and mood or anxiety disorders can achieve large responses to preventive pharmacologic and behavioral therapies. Emerging research is developing and evaluating behavioral treatments designed to manage cooccurring migraine and mood or anxiety disorders. Stigma related to psychiatric disorders has been well characterized, and could exacerbate extant migraine-related stigma. SUMMARY: Anxiety and mood disorders are prevalent in people with migraine, although not ubiquitous. Psychiatric comorbidity is associated with greater migraine symptoms and disability; however, people with comorbid depression or anxiety are amenable to preventive migraine treatment. Research regarding migraine treatment strategies optimized for people with comorbid psychiatric disorders is critical to advancing care and reducing stigma for this important subpopulation of people with migraine. PMID- 26886354 TI - Thinking globally to meet local needs: autism spectrum disorders in Africa and other low-resource environments. AB - PURPOSE OF REVIEW: Most people with autism spectrum disorders (ASDs) live in low and middle-income countries, yet almost everything we know about ASD comes from high-income countries. Here we review recent research from Africa, with some references to research in other low-resource environments. We examine publications on screening and diagnosis, intervention, clinical presentation of ASD, cultural perspectives, and neuroscience and technology. RECENT FINDINGS: Open-access screening and diagnostic tools represent a positive, but nontrivial, future goal. Recent efforts at 'low intensity' community-based interventions are encouraging, but many significant scalability challenges remain. Proposals that ASD in Africa is more severe and overrepresented in high socioeconomic families are likely to be attributable to ascertainment biases and the absence of standardized phenotyping tools. Cultural perspectives and innovative use of technology and neuroscience have the potential to generate novel strategies of global relevance, but research priorities have to be determined by local needs. SUMMARY: To have a real impact on clinical services, training, and research in local communities, clinician-scientists should start by thinking globally. ASD research in Africa and other low-resource environments remains limited and of questionable quality and highlights the need to build high-quality research capacity in these low-resource environments. PMID- 26886356 TI - The migraine postdrome. AB - PURPOSE OF REVIEW: Migraine is a common, disabling neurological disorder that affects up to 12% of the world population. Its pathophysiology is incompletely described. Of the various phases of migraine, the migraine postdrome is the least studied and hence the least understood. RECENT FINDINGS: Electronic diary studies show patients are left disabled with non-headache symptoms in the migraine postdrome. Hence, the importance of understanding the phase better and ensuring that more effective treatments become available in the future to cut down the morbidity associated with this phase. SUMMARY: The disability related to migraine is not limited to the headache phase and pans out to include the postdrome phase. The migraine postdrome needs to be studied more as this may improve our overall understanding of migraine mechanisms and also treat the concurrent symptoms better. PMID- 26886358 TI - Progress from genome-wide association studies and copy number variant studies in epilepsy. AB - PURPOSE OF REVIEW: The pace of gene discovery in epilepsy remains frenetic. Although most recent discoveries have come from next-generation sequencing studies, there has also been important progress using more established methodologies, such as genome-wide association studies (GWASs) and copy number variants (CNVs) identified through array-based techniques. Progress in these areas over the last year is reviewed. RECENT FINDINGS: The first meta-analysis of GWASs was a landmark development for the epilepsy community, though more sizeable studies are sorely needed. Other GWASs point to potentially interesting discoveries, and are in need of replication and follow-up. Copy number variation is emerging as an important genetic contribution to causation across a wide range of epilepsies, with a number of discoveries in epilepsies from the common, such as genetic generalized epilepsies, to the individually comparatively rare, such as particular epileptic encephalopathies. The first studies of CNV analysis from next-generation sequencing data, and of the combination of sequencing and array based data, have also emerged, allowing more comprehensive genetic evaluation of specific phenotypes. SUMMARY: GWASs based on single nucleotide polymorphisms, and CNV analyses based on a variety of data sources, retain a place in the discovery of causation and susceptibility in the epilepsies, and will probably become more powerful in the near future through the use of large-scale next-generation sequencing studies. There are still discoveries to come through these routes. PMID- 26886359 TI - Predicting epilepsy surgery outcome. AB - PURPOSE OF REVIEW: This review summarizes recent evidence on the seizure, safety, cognitive and psychosocial outcomes of epilepsy surgery and their predictors. RECENT FINDINGS: Risks of serious surgical complications have dramatically decreased over years to drop below 1% for temporal lobe resections. Although chances of postoperative seizure freedom largely vary between recent series, some data suggest that long-term seizure control might be achieved in over 80% of patients with mesial temporal lobe epilepsy or neocortical epilepsy associated with type 2 focal cortical dysplasia, and in up to two-thirds of patients with extratemporal lobe epilepsy. In the same conditions, some recent series challenge the classic view that a normal MRI is associated with worse outcome, an important finding given the greater proportion of MRI-negative patients now considered for epilepsy surgery. SUMMARY: These provocative findings appear to partly reflect the advances in the optimal use or postprocessing of neuroimaging data, as well as the identification of temporal plus epilepsy. This latter condition, which is characterized by normal MRI in half of patients and very poor outcome following anterior temporal lobectomy, was found to represent the main predictor of temporal lobe epilepsy surgery failures. Postoperative cognitive and quality-of life outcomes, which partly depend on seizure control, are also influenced by antiepileptic drugs and psychiatric comorbidities. PMID- 26886357 TI - Progress in autoimmune epileptic encephalitis. AB - PURPOSE OF REVIEW: Autoimmune epileptic encephalopathy is a potentially treatable neurological syndrome characterized by the coexistence of a neuronal antibody in serum and, often, cerebrospinal fluid. Patients present with combinations of seizures, neuropsychiatric features, movement disorder, and cognitive decline, but some patients have isolated seizures either at first presentation or during their illness. This review summarizes our current understanding of the roles of specific neuronal antibodies in epilepsy-related syndromes and aims to aid the clinician in diagnosis and treatment. RECENT FINDINGS: Antigen discovery methods in three neuroimmunology centres independently identified antibodies to different subunits of the gamma amino butyric acid-A receptor; high levels of these antibodies were found mainly in patients with severe refractory seizures. These and other antibodies were also found in a proportion (<10%) of children and adults with epilepsy. A clinical study comparing immunotherapy in patients with autoantibodies or without an identified target antigen found neuroinflammatory features were predictive of a therapeutic response. New in-vitro and in-vivo studies, and spontaneous animal models, have confirmed the pathogenicity and epileptogenicity of neuronal antibodies and their relevance to other mammals. SUMMARY: Neuronal antibodies are an important cause of autoimmune epileptic encephalopathy, early recognition is important as there may be an underlying tumour, and early treatment is associated with a better outcome. In the absence of an antibody, the clinician should adopt a pragmatic approach and consider a trial of immunotherapy when other causes have been excluded. PMID- 26886360 TI - Recent advances in status epilepticus. AB - PURPOSE OF REVIEW: This review discusses advances in the understanding of the mechanisms of status epilepticus and its current treatment approaches. Many of these have been topics at the 5th London-Innsbruck Colloquium on status epilepticus 2015. RECENT FINDINGS: A new definition and classification of status epilepticus was proposed, which is expected to improve treatment and stimulate research. A better understanding of the failure of seizure suppressing mechanisms and the initiation of self-sustaining seizures begins to translate into the clinical arena. Drugs, such as allopregnanolone, cannabinoids, sec butylpropylacetamide and valnoctamide, may better target these seizure perpetuating mechanisms. The concept of combinatorial treatments has further developed, but yet trials in humans are lacking. A new prognostic outcome-score and electroencephalography-criteria for nonconvulsive status epilepticus are ready for clinical use. Alternative routes, such as intranasal or buccal, have been explored in a number of trials suggesting that intramuscular midazolam is at least as effective as intravenous lorazepam and buccal or intranasal midazolam is at least as effective as rectal diazepam. SUMMARY: Despite progress in basic science, translation into the clinical field remains difficult. There is hope, that the two large phase III studies in the established and refractory status that started recruitment in 2015 will better inform the clinicians in this emergency situation. PMID- 26886361 TI - Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain. AB - Extracts rich in cysteine proteases obtained from fruits of Pseudananas macrodontes (Pm), Bromelia balansae (Bb), and B. hieronymi (Bh) have previously shown an anti-inflammatory effect on animal models. Given the close relationship between hemostasis and inflammation, it is attractive to investigate therapeutic agents capable of modulating both systems. The aim of this work was to study the effect of Pm, Bb, and Bh on fibrin(ogen) and blood coagulation compared with stem bromelain (Bro). Action on fibrinogen was electrophoretically and spectrophotometrically evaluated, fibrinolytic activity was measured both electrophoretically and by the fibrin plate assay, and the effect on blood coagulation was studied by conventional coagulation tests (PT and APPT). All extracts showed the same proteolytic preference for fibrinogen subunits, that is Aalpha > Bbeta, whereas gamma was partially hydrolyzed by 100-fold concentration increase. Unlike Bro, cysteine proteases of Pm, Bb, and Bh increased absorbance at 540 nm of fibrinogen solution, suggesting thrombin-like activity, which was time-dependent and reached maximum values at lower concentration. All extracts showed the same proteolytic preference for fibrin subunits; however Pm, Bb, and Bh showed lower fibrinolytic activity than Bro at the assayed concentrations. Although Bb acted only as anticoagulant, Pm, Bh, and unexpectedly Bro showed dual action on blood coagulation: at low concentration showed procoagulant effect and at high concentration anticoagulant effect. Results reveal new plant species as potential sources of pharmacological agents for the treatment of a wide range of hemostatic disorders as well as to wound healing. PMID- 26886362 TI - Patterns of international normalized ratio values among new warfarin patients with nonvalvular atrial fibrillation. AB - Limited information exists regarding the relationship between international normalized ratio (INR) control/stability and the discontinuation of warfarin therapy among patients with nonvalvular atrial fibrillation (NVAF). This study evaluated the association between INR stabilization and warfarin discontinuation and assessed INR patterns before and after INR stabilization among patients (>=18 years) with NVAF who newly initiated warfarin (Veterans Health Administration datasets; October 1, 2007 through September 30, 2012). Achievement of INR stabilization (>=3 consecutive in-range therapeutic INR measurements >=7 days apart) was examined from warfarin initiation through the end of warfarin exposure. Proportion of time in therapeutic range during warfarin exposure was calculated (Rosendaal method) and categorized as at least 60% or less than 60%. Among 34 346 patients, 49.4% achieved INR stabilization (mean time to stabilization, 98 days). Approximately 40% of INR values were out-of-range, even after achieving stabilization. During 30 days following an INR 4.0 or higher, patients had more INR testing than the overall mean (2.51 vs. 1.67 tests). Warfarin discontinuation was 4.2 times more likely among patients without INR stabilization versus those with INR stabilization (P < 0.00001). Patients with poor INR control (time in therapeutic range <60%) were 1.76 times more likely to discontinue warfarin within 1 year (P < 0.0001). INR stabilization is a better predictor of warfarin discontinuation than poor INR control. Improved approaches are necessary to maintain appropriate anticoagulation levels among patients with NVAF. PMID- 26886363 TI - A case of congenital prothrombin deficiency and idiopathic thrombocytopenic purpura in a pregnant female. AB - Hereditary prothrombin deficiency is an autosomal recessive disorder with an estimated incidence of 1 in 2 million . Presentation of the disease is variable; however, it is usually associated with moderate to severe bleeding tendencies including muscle hematomas, hemarthrosis, intracranial, mucosal, and postoperative bleeding. Here we report a case of a 35-year-old pregnant woman with congenital hypoprothrombinemia and idiopathic thrombocytopenic purpura, review the literature, and discuss its epidemiology, presentation, diagnosis, and treatment. PMID- 26886364 TI - [Accuracy of probabilistic record linkage for identifying deaths in a cohort of patients with decompensated heart failure]. AB - Probabilistic record linkage has been used increasingly to identify outcomes in cohort studies. This study aimed to assess the method's accuracy for identifying deaths in a cohort of 450 patients admitted to a university hospital for decompensated heart failure over a six-year period. Vital status of cohort members was determined from electronic patient file data (gold standard). OpenRecLink software was used to link cohort records with those from the Mortality Information System, aimed at identifying deaths. Only 53.6% of patients had vital status known at the end of follow-up, and 59.3% of these had died. The method showed 97.9% sensitivity, 100% specificity, 100% positive predictive value, 97% negative predictive value, and 98.8% accuracy. The results suggest probabilistic record linkage as a valuable tool for identifying deaths in cohort studies. PMID- 26886365 TI - Innovation, quality and quantity: choose two. PMID- 26886366 TI - [Determinants of equity in financing medicines in Argentina: an empirical study]. AB - Medicines are an important part of household health spending. A progressive system for financing drugs is thus essential for an equitable health system. Some authors have proposed that the determinants of equity in drug financing are socioeconomic, demographic, and associated with public interventions, but little progress has been made in the empirical evaluation and quantification of their relative importance. The current study estimated quantile regressions at the provincial level in Argentina and found that old age (> 65 years), unemployment, the existence of a public pharmaceutical laboratory, treatment transfers, and a health system orientated to primary care were important predictors of progressive payment schemes. Low income, weak institutions, and insufficient infrastructure and services were associated with the most regressive social responses to health needs, thereby aggravating living conditions and limiting development opportunities. PMID- 26886367 TI - Walking, body mass index, and self-rated health in a representative sample of Spanish adults. AB - Obesity and physical inactivity (PI) are risk factors for chronic diseases and are associated with lifestyle and environmental factors. The study tested the association between PI, body mass index (BMI), and self-rated health in a representative sample of the Spanish adult population (N = 21,486). The sample included 41.5% men, with mean age 52.3 years (+/- 18.03), and age range 20-82 years. Prevalence of overweight/obesity was 34.2%/12.7% in women and 52.1%/12.7% in men (p < 0.001 for obesity in both sexes). 53% of women and 57.5% of men met recommended levels of physical activity by walking (>= 150 minutes/week). According to logistic regression analysis, individuals that walked less had higher risk of overweight or obesity. Data from the population-based surveillance study support suggestions that regular walking by adults is associated with positive self-rated health and better BMI profile. Obesity and low/very low self rated health have low prevalence rates to meet the recommendations. PMID- 26886368 TI - [Prevalence of illicit drug use and associated factors during pregnancy in the BRISA cohort]. AB - This study analyzes the prevalence of illicit drug use and associated factors during pregnancy. This was a cross-sectional study of participants in the BRISA prenatal care cohort. Frequencies and hierarchical logistic regression were used. Estimated prevalence rates were 1.45% for illicit drug use, 22.32% for alcohol consumption, and 4.22% for smoking. The study population was mostly young (81% in the 20-34-year bracket), with 9 to 11 years of schooling (75.55%), with more than half of the women outside the workforce (52.18%), and in economic class "C" (67.61%). Pregnant women showed a high level of stress (24.46%), moderate to intense anxiety (40.84%), and severe depressive symptoms (28.8%). Approximately half (49.72%) of the pregnant women reported some type of violence, and they had wide networks (72.77%) and low social support (65.21%). Use of legal drugs, high stress levels, and single parenthood were independently associated with illicit drug use in pregnancy. PMID- 26886369 TI - [Litigation and the right to health in Argentina]. AB - This article explores the characteristics of lawsuits for obtaining access to healthcare through the Argentine Supreme Court and reflects on the potential to influence health rights and equity in a context of growing litigation. An analysis of documents from 125 lawsuits with verdicts issued from 1994 to 2013 showed a majority of individual claims (88% of claimants were individual physical persons), and of claimants covered by social security or private insurance (64%) with typical private legal counsel (87% claiming coverage of a medical service). 75% of the verdicts simply ordered the provision of the claimed health services, without highlighting failures in the healthcare system or mandating measures to promote equity and guarantee the right to health for other persons subject to the same situation as the claimant. Thus far, litigation in health has failed to actively promote either health equity, the right to health, or inter institutional dialogue. PMID- 26886373 TI - Melanotic Neuroectodermal Tumor of Infancy in the Epididymis: A Brief Report and Review of the Role of Chemotherapy in Management. AB - Melanotic neuroectodermal tumor of infancy is a rare benign tumor of neural crest origin. The tumor generally presents in the jawbones; however, it occasionally occurs in extracranial sites. Although 95% of these tumors present within the first year of life and 15% in extracranial locations, we report an unusual case of a 15-month-old male with melanotic neuroectodermal tumor of infancy of the epididymis. The patient underwent orchiectomy without adjuvant chemotherapy or radiation. Twenty months later, there was no sign of recurrence. In addition, we discuss the role of chemotherapy and radiation and the potential importance of molecular genetics in establishing guidelines for management. PMID- 26886370 TI - Does a Water Protocol Improve the Hydration and Health Status of Individuals with Thin Liquid Aspiration Following Stroke? A Randomized Controlled Trial. AB - The benefit of water protocols for individuals with thin liquid aspiration remains controversial, with mixed findings from a small number of randomized controlled trials (RCTs). This study aimed to contribute to the evidence of the effectiveness of water protocols with a particular emphasis on health outcomes, especially hydration. An RCT was conducted with patients with known thin liquid aspiration post stroke randomized to receiving thickened liquids only or a water protocol. For the 14 participants in rehabilitation facilities whose data proceeded to analysis, there was no difference in the total amount of beverages consumed between the water protocol group (mean = 1103 ml per day, SD = 215 ml) and the thickened liquids only group (mean = 1103 ml, SD = 247 ml). Participants in the water protocol group drank on average 299 ml (SD 274) of water but offset this by drinking less of the thickened liquids. Their hydration improved over time compared with participants in the thickened liquids only group, but differences between groups were not significant. Twenty-one percent of the total sample was diagnosed with dehydration, and no participants in either group were diagnosed with pneumonia. There were significantly more diagnoses of urinary tract infection in the thickened liquids only group compared to the water protocol group (chi (2) = 5.091, p = 0.024), but no differences between groups with regard to diagnoses of dehydration (chi (2) = 0.884, p = 0.347) or constipation (chi (2) = 0.117, p = 0.733). The findings reinforce evidence about the relative safety of water protocols for patients in rehabilitation post stroke and provide impetus for future research into the potential benefits for hydration status and minimizing adverse health outcomes. PMID- 26886371 TI - Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence. AB - Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment. PMID- 26886372 TI - Helicobacter pylori-elicited induction in gastric mucosal matrix metalloproteinase-9 (MMP-9) release involves ERK-dependent cPLA2 activation and its recruitment to the membrane-localized Rac1/p38 complex. AB - Matrix metalloproteinases (MMPs) are a family of endopeptidases implicated in a wide rage of degenerative and inflammatory diseases, including Helicobacter pylori-associated gastritis, and gastric and duodenal ulcer. As gastric mucosal inflammatory responses to H. pylori are characterized by the rise in MMP-9 production, as well as the induction in mitogen-activated protein kinase (MAPK) and Rac1 activation, we investigated the role of Rac1/MAPK in the processes associated with the release of MMP-9. We show that H. pylori LPS-elicited induction in gastric mucosal MMP-9 release is associated with MAPK, ERK and p38 activation, and occurs with the involvement of Rac1 and cytosolic phospholipase A2 (cPLA2). Further, we demonstrate that the LPS-induced MMP-9 release requires ERK-mediated phosphorylation of cPLA2 on Ser(505) that is essential for its membrane localization with Rac1, and that this process necessitates p38 participation. Moreover, we reveal that the activation and membrane translocation of p38 to the Rac1-GTP complex plays a pivotal role in cPLA2-dependent enhancement in MMP-9 release. Hence, our findings provide a strong evidence for the role of ERK/cPLA2 and Rac1/p38/cPLA2 cascade in H. pylori LPS-induced up regulation in gastric mucosal MMP-9 release. PMID- 26886374 TI - Epstein-Barr Virus-related Posttransplant Lymphoproliferative Disorder in Children: A Single-institution Experience. AB - We report 4 pediatric cases of biopsy-proven posttransplant lymphoproliferative disorder (PTLD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). All cases showed diffuse staining with latent membrane protein-1 in immunohistochemistry. The median age at transplant of 4 patients with PTLD was 10.1 years (range, 2.2 to 13.2 y). The median interval between HSCT and the diagnosis of PTLD was 5.5 months (range, 4 to 8 mo). All patients were treated with rituximab at dosage of 375 mg/m at weekly intervals. Reduction of immunosuppression was warranted in all cases. All patients survived with median follow-up duration of 27 months. Although PTLD has been rare following allogeneic HSCT, reduction of immunosuppression combined with rituximab yielded significant response rates in patients with this infrequent but potentially lethal complication. The preliminary finding of this study demonstrated that severe aplastic anemia is closely associated with the development of PTLD in children. PMID- 26886375 TI - Gorham-Stout Disease Successfully Treated With Sirolimus and Zoledronic Acid Therapy. AB - Gorham-Stout disease is a life-threatening disorder often manifested by lymphatic malformation and osteolysis. Unfortunately, available therapies are not uniformly effective and often carry substantial morbidity. We report an 18-year-old male with Gorham-Stout disease manifested by lytic rib lesions and an intractable pleural effusion that responded dramatically to the combination of the mammalian target of rapamycin (mTOR) inhibitor sirolimus and the aminobisphosphonate zoledronic acid after failing interferon therapy. This tolerable therapeutic combination has demonstrated synergism in preclinical cancer models and merits further study in vascular anomalies. PMID- 26886376 TI - Assessing the Immunogenic Response of a Single Center's Pneumococcal Vaccination Protocol in Sickle Cell Disease. AB - Sickle cell disease (SCD) is the most common inherited hematologic disorder in the United States. Patients with SCD are at increased risk of invasive pneumococcal disease and are reliant on both early penicillin prophylaxis and antipneumococcal vaccination for prevention of infection. Although studies examining vaccine response have demonstrated a drop-off of titer response after 3 years, an optimal vaccination regimen has not been identified. Our study sought to assess the immunogenicity of our center's pneumococcal vaccination strategy, which included Prevnar (PCV-7) (before the introduction of PCV-13) followed by Pneumovax (PPV-23) given routinely at 2 and 5 years of age and then every 5 years thereafter. Our goal was to assess vaccine response in a population of patients with SCD who had received vaccines according to this regimen using multiplex bead analysis. Our study demonstrated a significant percentage of persons with SCD do not maintain a sufficient vaccination response to PPV-23 for 5 years. Our study revealed that only 36% of patients had protective levels of antipneumococcal antibody titers at an average of 37 months after vaccination. Most alarmingly, within the group of patients with subtherapeutic titers, 64% demonstrated vaccine response to <25% of the tested serotypes. These findings were significantly associated with duration of time since last vaccine administration, but the mean age of lack of response was below the 3-year window where vaccine response was previously reported to wane. Our results indicate antipneumococcal immunity may not be optimally maintained using this vaccination strategy in patients with SCD leaving them vulnerable to invasive pneumococcal disease. Many pediatric hematologists stop prophylactic penicillin at 5 years of age making these results alarming. We recommend further investigation into an optimal vaccine schedule and monitoring of antipneumococcal titers in at-risk patients. PMID- 26886377 TI - Myoepithelial Carcinoma: The Role of Radiation Therapy. A Case Report and Analysis of Data From the Surveillance, Epidemiology, and End Results (SEER) Registry. AB - PURPOSE/OBJECTIVE: The role of radiation therapy in the treatment of myoepithelial carcinoma (MC) is unknown. We present a case of a high-grade soft tissue MC in a pediatric patient and retrospectively examine the effect of postoperative radiation on survival in patients with MC. MATERIALS AND METHODS: Our patient was treated with 4 cycles of ifosfamide, cisplatin, and etoposide followed by 3 cycles of ifosfamide vincristine and etoposide. Radiation was delivered to a total dose of 5580 cGy in 180 cGy/fraction to the surgical bed with a 2 cm margin starting after the third cycle of chemotherapy. The Surveillance, Epidemiology, and End Results (SEER) registry database was queried for cases of surgically resected MC. Retrospective analysis was performed with the endpoint of overall survival (OS). RESULTS: Two hundred thirty-four cases of MC were identified; for 62 of these cases, the grade of the tumor wasidentified. Of these 62 patients, 27 received postoperative radiation. OS was improved with adjuvant radiation therapy in patients with grade III or IV MC (P<0.01) as determined by the log-rank test. CONCLUSIONS: This analysis of SEER data showed an OS benefit with adjuvant radiation therapy in the treatment of high-grade MC. Physicians should report all cases of MC to improve clinical decision making in the treatment of this rare disease. PMID- 26886378 TI - True Evidence-Based Care for Posttraumatic Stress Disorder in Military Personnel and Veterans. PMID- 26886379 TI - What would be missed if we didn't screen men who have sex with men for oral chlamydia trachomatis? A cross-sectional study. AB - Background This study aimed to describe oropharyngeal chlamydia (OCT) in gay and bisexually active men (GBM) attending a large urban sexual health clinic in Sydney and determine what proportion of cases would be missed if screening was not routine. METHODS: Retrospective data were extracted for all GBM with a positive OCT result between 1 October 2012 and 31 April 2014. The control group consisted of patients who had a negative OCT result on their first visit during the study period, and each patient was only counted once. RESULTS: A total of 74 of 2920 GBM (0.03, 95% CI: 0.02-0.03) were diagnosed with OCT. The 2920 GBM had a total of 11226 OCT tests performed, demonstrating OCT test positivity of 0.006 (95% CI: 0.005-0.008). A total of 62 sexually transmissible infections (STIs) were diagnosed at other sites: 34 rectal chlamydia (CT), 12 throat gonorrohea (GC), 7 urine CT, 7 rectal GC, 1 infectious syphilis and 1 non-gonoccal urethritis (NGU) case. Of the 74 OCT cases, 56 (0.76, 95% CI: 0.64-0.85) were treated with Azithromycin; 51 (69%) as part of standard treatment for their STI co-infection (34 rectal CT, 12 throat GC, 7 urine CT, 7 rectal GC, 1 NGU case) and a further five (7%) were treated as contacts. The remaining 18 people (0.24, 95% CI: 0.15-0.36) would not have been treated unless they were tested specifically for OCT. CONCLUSION: Overall, two-thirds of the OCT cases received appropriate treatment and only a small number of cases would have been missed had routine screening not been performed. With an extremely low overall test positivity of 0.6%, screening for OCT at our service adds little to population level health control. PMID- 26886380 TI - Exploring the Microbiome in Heart Failure. AB - Recent years have brought interesting insights into the human gut microbiota and have highlighted its increasingly recognized impact on cardiovascular (CV) diseases, including heart failure (HF). Changes in composition of gut microbiota, called dysbiosis, can trigger systemic inflammation, which is known to be involved in the pathophysiology of HF. Trimethylamine N-oxide (TMAO), which is derived from gut microbiota metabolites of specific dietary nutrients, has emerged as a key contributor to cardiovascular disease pathogenesis. Elevated TMAO levels have been reported to be associated with poor outcomes in patients with both HF and chronic kidney disease (CKD). Dysbiosis of gut microbiota can contribute to higher levels of TMAO and the generation of uremic toxins, progressing to both HF and CKD. Therefore, this bidirectional relationship between HF and CKD through gut microbiota may be a novel therapeutic target for the cardiorenal syndrome. However, the mechanisms by which gut microbiota could influence the development of heart failure are still unknown, and there are still some questions regarding the causative effects of TMAO and the underlying mechanistic link that explains how TMAO might directly or indirectly promote CV diseases including HF. Further studies are warranted to clarify the function of TMAO on the pathophysiology of cardiorenal syndrome and the handling of TMAO levels by the kidneys. PMID- 26886381 TI - Evolving Concepts of Pulmonary Hypertension Secondary to Left Heart Disease. AB - Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension. Although its pathophysiology remains incompletely understood, it is now well recognized that the presence of pulmonary hypertension is associated with a worse prognosis. Right ventricular failure has independent and additive prognostic value over pulmonary hypertension for adverse outcomes in left heart disease. Recently, several new terminologies have been introduced to better define and characterize the nature and severity of pulmonary hypertension. Several new treatment options including the use of pulmonary arterial hypertension specific therapies are being considered, but there is lack of evidence. Here, we review the recent advances in this field and summarize the diagnostic and therapeutic modalities of use in the management of pulmonary hypertension associated with left heart disease. PMID- 26886382 TI - Decreased Toll-Like Receptor 2 and Toll-Like Receptor 7/8-Induced Cytokines in Parkinson's Disease Patients. AB - OBJECTIVES: Toll-like receptors (TLRs) are expressed in several immune cells including blood monocytes and resident macrophages, such as microglia in the central nervous system. TLRs recognize pathogen- or damage-associated molecular patterns, leading to the release of inflammatory and toxic molecules, which can contribute to neuroinflammation associated with Parkinson's disease (PD). The aim of this study was to compare the potential of peripheral blood cells from PD patients or healthy subjects to produce cytokines after exposure to TLR agonists, and to investigate TLR2 and TLR4 expression on monocyte subsets. METHODS: Twenty one patients and 21 healthy controls were recruited. Patients were evaluated according to the Unified Parkinson's Disease Rating Scale, and Hoehn and Yahr stage. Cytokines were measured in supernatants of whole blood cultures after incubation with TLR2, TLR4, or TLR7/8 agonists, by cytometric bead array. Expression of CD14, CD16, TLR2, and TLR4 was analyzed by cytometry. RESULTS: Patient blood cells produced lower levels of cytokines in response to TLR2 and also after TLR7/8/R848 activation than controls. Percentages of CD14+CD16+ or CD14+CD16- monocytes and TLR2 and TLR4 expression were similar between patients and controls. CONCLUSIONS: Blood leukocyte TLR2 and TLR7/8 responses are impaired in PD. This was neither associated with imbalance in monocyte subsets nor with TLR2/TLR4 expression on these cells. The association between a decreased TLR response in periphery and damage of brain in PD must be further investigated. PMID- 26886383 TI - Effect of using a laryngeal tube on the no-flow time in a simulated, single rescuer, basic life support setting with inexperienced users. AB - BACKGROUND: The laryngeal tube (LT) is a recommended alternative to endotracheal intubation during advanced life support (ALS). Its insertion is relatively simple; therefore, it may also serve as an alternative to bag mask ventilation (BMV) for untrained personnel performing basic life support (BLS). Data support the influence of LT on the no-flow time (NFT) compared with BMV during ALS in manikin studies. METHODS: We performed a manikin study to investigate the effect of using the LT for ventilation instead of BMV on the NFT during BLS in a prospective, randomized, single-rescuer study. All 209 participants were trained in BMV, but were inexperienced in using LT; each participant performed BLS during a 4-min time period. RESULTS: No significant difference in total NFT (LT: mean 81.1 +/- 22.7 s; BMV: mean 83.2 +/- 13.1 s, p = 0.414) was found; however, significant differences in the later periods of the scenario were identified. While ventilating with the LT, the proportion of chest compressions increased significantly from 67.2 to 73.2%, whereas the proportion of chest compressions increased only marginally when performing BMV. The quality of the chest compressions and the associated ventilation rate did not differ significantly. The mean tidal volume and mean minute volume were significantly lower when performing BMV. CONCLUSIONS: The NFT was significantly shorter in the later periods in a single-rescuer, cardiac arrest scenario when using an LT without previous training compared with BMV with previous training. A possible explanation for this result may be the complexity and workload of alternating tasks (e.g., time loss when reclining the head and positioning the mask for each ventilation during BMV). PMID- 26886384 TI - [Implementation of regularly performed resuscitation training at a hyperbaric treatment center]. AB - BACKGROUND: Medical emergency situations and even cardiac arrest can occur during treatment of patients in therapeutic hyperbaric chambers just as in other clinical departments; therefore, high quality structured management should be implemented for dealing with emergencies in this special working area. To ensure this the emergency medical treatment should not only be performed according to the current state of medical knowledge but needs to take the special features of the hyperbaric environment including safety aspects into account. METHOD: This article presents a description of the implementation and effects of routine emergency and resuscitation training at a center for hyperbaric medicine. RESULTS: By simulation of emergencies in a hyperbaric chamber it rapidly became clear that the treatment of medical emergencies and cardiac arrest under hyperbaric conditions has some special features and due to safety aspects cannot always be performed according to current medical guidelines. At the time of this simulation in a real life working environment, previously unknown structural and logistic problems became obvious whereby the solutions contributed to a significant improvement of structural and process quality and could potentially also improve the outcome quality. Furthermore, a positive and lasting learning effect in the fields of quality of resuscitation measures, organization of the workplace, communication skills, logistics and safety aspects was detectable by analyzing participant performance over a period of 4 years. On the part of the participating staff a positive feedback and high acceptance of emergency simulator training was confirmed. CONCLUSION: Through annual compulsory emergency training of the complete staff of the hyperbaric unit at the actual workplace, a structural and confident approach to dealing with emergencies and resuscitation situations was observed. By the use of on-site simulator training even in specialized hospital units, deficits and tentativeness regarding logistics, course of action, organization and communication in emergency situations can be minimized to provide optimum patient care in a real life emergency situation by focusing on the medical measures. PMID- 26886385 TI - Radiographic vertebral fractures develop in patients with ankylosing spondylitis during 4 years of TNF-alpha blocking therapy. AB - OBJECTIVES: To determine the prevalence and incidence of radiographic vertebral fractures in ankylosing spondylitis (AS) patients treated with TNF-alpha blocking therapy for 4 years and to explore the relationship with patient characteristics, clinical assessments, radiographic damage, and bone mineral density (BMD). METHODS: This study included consecutive AS patients with active disease from the Groningen Leeuwarden AS (GLAS) cohort treated with TNF-alpha blocking therapy for 4 years and with available thoracic and lumbar radiographs at baseline and at 4 years. Vertebral fractures were assessed by two readers (mild: >=20-<25%, moderate: >=25-<40%, severe: >=40% reduction in vertebral height). RESULTS: In 27 of 105 (26%) AS patients, radiographic vertebral fractures were observed at baseline. These patients were significantly older, had larger occiput-to-wall distance, and more spinal radiographic damage. During 4 years of TNF-alpha blocking therapy, 21 (20%) patients developed at least one new fracture. Older age, smoking, higher BASFI, low lumbar spine BMD (Z-score <=-2), presence of moderate vertebral fractures, and use of anti-osteoporotic treatment at baseline were associated with the development of new fractures. Most fractures were mild and occurred in the thoracic spine. The improvement in lateral spinal mobility and lumbar spine BMD during treatment was significantly less in patients with new fractures (median change of 0.8 vs. 2.8 cm and 0.3 vs. 0.8 Z-score, respectively). CONCLUSIONS: The prevalence of radiographic vertebral fractures was high in AS patients with active disease. Although clinical assessments and BMD improved significantly, new vertebral fractures still developed during 4 years of TNF-alpha blocking therapy. PMID- 26886386 TI - Characteristics and outcomes of transjugular intrahepatic portosystemic shunt recipients in the VA Healthcare System. AB - BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement is an effective treatment for complications of portal hypertension. We aimed to describe post-TIPS mortality and its predictors in the modern era of covered stents. PATIENTS AND METHODS: We identified patients with cirrhosis who underwent TIPS insertion at Veterans Affairs Healthcare facilities nationally from 2004 to 2014 (n=703), most of which (95%) were performed as elective procedures. We followed patients until the date of death, transplantation, or the end of the observation period. RESULTS: TIPS recipients had a mean age of 59.3 years (SD 8) and 97% were men. The mean Model for End Stage Liver Disease (MELD) score was 13 (SD 4.8); 47% had hepatitis C virus (HCV) infection, 48% had variceal hemorrhage, and 40% had ascites. During a mean follow-up of 1.72 years (SD 1.9), 57.5% of TIPS recipients died (n=404) and only 5.3% underwent liver transplantation (n=37). The median survival after TIPS was 1.74 years (interquartile range 0.3-4.7). Thirty-day mortality after TIPS was 11.6% [95% confidence interval (CI) 9.4-14.2], 1-year mortality was 40.3% (95% CI 36.7 44.2), and 3-year mortality was 61.9% (95% CI 57.9-66.0). Independent predictors of post-TIPS mortality included medical comorbidity burden, low albumin, HCV infection, and high MELD score (or high international normalized ratio and bilirubin when the components of the MELD score were analyzed individually). TIPS revision was performed at least once in 27.3% of TIPS recipients. CONCLUSION: TIPS should not be considered simply as a bridge to transplantation. Burden of extra-hepatic comorbidities, HCV infection, and low serum albumin strongly predict post-TIPS mortality in addition to the MELD score. PMID- 26886387 TI - Uric acid in nonalcoholic fatty liver disease. PMID- 26886390 TI - Kallikrein-related peptidases (KLKs) and the hallmarks of cancer. AB - The kallikrein-related peptidases (KLKs) represent the largest family of serine proteases within the human genome and are expressed in various tissues. Although they regulate several important physiological functions, KLKs have also been implicated in numerous pathophysiological processes, including cancer. Growing evidence describing the deregulation of KLK expression and secretion, as well as activation in various malignancies, has uncovered their potential as mediators of cancer progression, biomarkers of disease and as candidate therapeutic targets. The diversity of signalling pathways and proteolytic cascades involving KLKs and their downstream targets appears to affect cancer biology through multiple mechanisms, including those related to the hallmarks of cancer. The aim of this review is to provide an update on the importance of KLK-driven molecular pathways in relation to cancer cell traits associated with the hallmarks of cancer and to highlight their potential in personalized therapeutics. PMID- 26886391 TI - Staff members' perceived training needs regarding sexuality in residential aged care facilities. AB - The purpose of the article is to ascertain if staff members of residential aged care facilities (RACF) perceive the need for training regarding residents' sexuality, and what, if any, benefits from the training were perceived, and to compare perceived benefits of training between care assistants and professional/managerial staff. Interviews were conducted with 53 staff members of five different RACF in Spain. Their responses to two semistructured questions were transcribed verbatim and submitted to content analysis. Results show that most interviewees said they lacked training about sexuality and aging. Two potential highlighted benefits of the training are knowledge/attitudinal (countering negative attitudes regarding sexuality) and procedural (developing common protocols and tools to manage situations related to sexuality). Care assistants and professional staff agreed on the need for training, though the former emphasized the procedural impact and the latter the knowledge/attitudinal benefits. The results suggest that RACF staff should have an opportunity to receive training on residents' sexuality, as sexual interest and behavior is a key dimension of residents' lives. PMID- 26886392 TI - Interactions between Carboxylic Acids and Heteroaromatics: A Rotational Study of Formic Acid-Pyridine. AB - The rotational spectra of four isotopologues of the 1:1 complex between formic acid and pyridine show that the two units are linked together through a "classical" (OH...N) and a weak (CH...O) hydrogen bond. The molecular system appears quite rigid and no effects of the internal motions have been observed in the spectrum. The dissociation energy obtained from the centrifugal distortion by applying an approximate model, 39.8 kJ/mol, is quite similar to the ab initio value, 41.7 kJ/mol. Its relatively high value suggests a small charge transfer to take place. PMID- 26886393 TI - Stereo-, Regio-, and Chemoselective [3 + 2]-Cycloaddition of (2E,4E)-Ethyl 5 (Phenylsulfonyl)penta-2,4-dienoate with Various Azomethine Ylides, Nitrones, and Nitrile Oxides: Synthesis of Pyrrolidine, Isoxazolidine, and Isoxazoline Derivatives and a Computational Study. AB - One-pot chemo-, regio-, and stereoselective synthesis of series of heterocyclic and spiroheterocyclic compounds was accomplished through mono- and bis[3 + 2] cycloaddition reactions of (2E,4E)-ethyl 5-(phenylsulfonyl)penta-2,4-dienoate as a dipolarophile with azomethine ylides, nitrones, and nitrile oxides in good yields. The structures of the products were established by spectroscopic techniques as well as by single-crystal XRD study, and DFT calculations were performed to further understand the mechanism of this [3 + 2]-cycloaddition reaction. PMID- 26886389 TI - Computed tomography of pulmonary changes in rheumatoid arthritis: carcinoembryonic antigen (CEA) as a marker of airway disease. AB - Rheumatoid arthritis (RA) classically affects the joints, but can present extra articular manifestations, including pulmonary disease. The present study aimed to identify possible risk factors or laboratory markers for lung involvement in RA, particularly the presence of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and tumor markers, by correlating them with changes observed on chest high-resolution computerized tomography (HRCT). This cross-sectional study involved RA patients who were examined and questioned by a specialist physician and later subjected to chest HRCT and blood collection for measurement of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), ACPA (anti-vimentin and/or anti-CCP3), and the tumor markers carcinoembryonic antigen (CEA), CA 125, CA 15-3, and CA 19-9. A total of 96 patients underwent chest HRCT. The most frequent findings were bronchial thickening (27/28.1 %) and bronchiectasis (25/26 %). RF was present in 63.2 % of patients (55/87), and ACPA (anti-vimentin or anti-CCP3) was present in 72.7 % of patients (64/88). CEA levels were high in 14 non-smokers (37.8 %) and 23 smokers (62.2 %). CA-19-9 levels were high in 6 of 86 patients (7.0 %), CA 15-3 levels were high in 3 of 85 patients (3.5 %), and CA 125 levels were high in 4 of 75 patients (5.3 %). Multivariate analysis indicated a statistically significant association between high CEA levels and the presence of airway changes in patients with RA (p = 0.048). CEA can serve as a predictor of lung disease in RA and can help identify individuals who require more detailed examination for the presence of respiratory disorders. PMID- 26886388 TI - Cardiac involvement in primary systemic vasculitis and potential drug therapies to reduce cardiovascular risk. AB - Cardiac involvement is common in primary systemic vasculitides and may be due to direct effect of the disease on the heart or due to therapy. We shall review involvement of the heart in the various forms of primary systemic vasculitis. Among anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), eosinophilic granulomatosis with polyangiitis most commonly involves the heart. Involvement of the heart confers poorer prognosis in AAV, which is also complicated by increased risk of cardiovascular events. Kawasaki's disease (KD) is the most common form of medium-vessel vasculitis to affect the heart, with coronary artery aneurysms being the most common manifestation. These predispose patients with KD to develop premature ischemic heart disease. Takayasu's arteritis is the most common large-vessel vasculitis to involve the heart and can result in aortic incompetence, myocarditis, or coronary heart disease. Involvement of the heart in Behcet's disease is usually in the form of intracardiac mass lesions, thrombosis, or endomyocardial fibrosis. Drugs used in the treatment of systemic vasculitis influence the risk of developing cardiovascular events. Corticosteroid therapy has been shown to increase the risk of myocardial infarction, whereas methotrexate, azathioprine, mycophenolate mofetil, rituximab, and anti-tumor necrosis alpha agents favorably modulate the risk of cardiovascular events, predominantly by dampening systemic inflammation. Awareness of cardiac involvement in vasculitis and accelerated cardiovascular risk in these patients should help clinicians to maximize the modulation of modifiable risk factors for heart disease in these individuals. PMID- 26886394 TI - Inflammatory Contribution of Platelets Revisited: New Players in the Arena of Inflammation. AB - Platelet-derived mediators, either in an autocrine or paracrine mode of action, regulate systemic and vascular inflammation as well as contribute to innate immune defense and also to regenerative mechanisms. This review reevaluates the impact of inflammatory mediators such as CXC-chemokine-Ligands, their receptors in modulating platelet functions and platelet survival, thereby influencing inflammatory or regenerative processes. We further explore the contribution of cyclophilin A and C-reactive protein in regulating thrombotic and hemostatic attributes of platelets. Moreover, we emphasize on the role of platelets as active components bridging the innate and adaptive immune responses, toll-like receptors on platelets, platelet interactions with the complement system, and platelet-derived thrombocidins exhibiting direct antimicrobial properties. As highlighted in this review, the multifaceted aspects of platelets and platelet derived factors encourage further investigations in this intriguing and expansive but largely uncharted area of research in platelet biology. PMID- 26886395 TI - Platelet Function Testing in Patients on Antiplatelet Medications. AB - Guidelines provide a Class IA recommendation for the use of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI). However, there is interindividual variability in the pharmacodynamic response to antiplatelet medications. Some patients present with a status of high on treatment platelet reactivity (HPR) during platelet function testing after standard doses of antiplatelet drugs, reflecting a failure to achieve adequate platelet inhibition. As an example, patients with HPR on clopidogrel are at increased risk for thrombotic events, particularly for stent thrombosis and myocardial infarction, but cardiovascular mortality is also elevated. On the contrary, low on-treatment platelet reactivity or an enhanced response to antiplatelet medications has been linked to a higher risk for bleeding. Although both thrombotic and bleeding events are multifactorial in origin, there is supportive evidence for the prognostic value of platelet function testing for risk prediction of both sides of the coin. However, although small studies have provided evidence that treatment adjustments based on platelet function testing results may improve clinical outcomes, the available randomized controlled trials showed no benefit of modifying antiplatelet treatment based on platelet function testing. This review presents the current evidence regarding platelet function testing in patients undergoing PCI. The prognostic value of platelet function testing regarding ischemic and bleeding events is highlighted. Furthermore, the value of platelet function testing for guiding treatment and possible explanations for the so-far negative trial results are presented. The possible future role of platelet function testing for individualized antiplatelet treatment regimens in high-risk patients will be also discussed. PMID- 26886396 TI - Platelet Function Tests in Bleeding Disorders. AB - Functional disorders of platelets can involve any aspect of platelet physiology, with many different effects or outcomes. These include platelet numbers (thrombocytosis or thrombocytopenia); changes in platelet production or destruction, or capture to the liver (Ashwell receptor); altered adhesion to vascular injury sites and/or influence on hemostasis and wound healing; and altered activation or receptor functions, shape change, spreading and release reactions, procoagulant and antifibrinolytic activity. Procoagulant membrane alterations, and generation of thrombin and fibrin, also affect platelet aggregation. The above parameters can all be studied, but standardization and quality control of assay methods have been limited despite several efforts. Only after a comprehensive clinical bleeding assessment, including family history, information on drug use affecting platelets, and exclusion of coagulation factor, and tissue deficits, should platelet function testing be undertaken to confirm an abnormality. Current diagnostic tools include blood cell counts, platelet characteristics according to the cell counter parameters, peripheral blood smear, exclusion of pseudothrombocytopenia, whole blood aggregometry (WBA) or light transmission aggregometry (LTA) in platelet-rich plasma, luminescence, platelet function analysis (PFA-100) for platelet adhesion and deposition to collagen cartridges under blood flow, and finally transmission electron microscopy to exclude rare structural defects leading to functional deficits. The most validated test panels are included in WBA, LTA, and PFA. Because platelets are isolated from their natural environment, many simplifications occur, as circulating blood and interaction with vascular wall are omitted in these assays. The target to reach a highly specific platelet disorder diagnosis in routine clinical management can be exhaustive, unless needed for genetic counseling. The elective overall assessment of platelet function disorder primarily aims at better management of hemostasis in case of emergency surgery or other interventions and acute bleeding events. PMID- 26886398 TI - Platelet Function Determined by Flow Cytometry: New Perspectives? AB - Flow cytometry enables studies of several different aspects of platelet function in response to a variety of platelet agonists. This can be done using only a small volume of whole blood, and also in blood with low platelet counts. These properties, together with the increasing number of flow cytometers available in hospitals worldwide, make flow cytometry an interesting option for laboratories interested in studies of platelet function in different clinical settings. This review focuses on practical issues regarding the use of flow cytometry for platelet function testing. It provides an overview of available activation markers, platelet agonists, and experimental setup issues. The review summarizes previous experience and factors important to consider to perform high-quality platelet function testing by flow cytometry. It also discusses its current use and possibilities and challenges for future use of flow cytometry in clinical settings. PMID- 26886397 TI - Platelets and Antiplatelet Therapy in Patients with Coronary Artery Disease and Diabetes. AB - Patients with diabetes mellitus are at increased risk of cardiovascular events. Despite advances in medical and interventional therapy, cardiovascular morbidity and mortality remains high in patients with diabetes. Although accelerated atherosclerosis has long been recognized as an underlying cause, recent studies suggest that changes in platelets and coagulation also play important roles. Patients with diabetes exhibit a prothrombotic milieu with hyperreactive platelets and coagulation abnormalities. Thus, prevention of cardiovascular events in patients with coronary artery disease (CAD) and diabetes involves a multifactorial approach including treatment of risk factors such as dyslipidemia, obesity, hypertension, hyperglycemia, and hypercoagulation. An impaired response to antiplatelet therapy has been consistently reported and optimization of this therapy seems appropriate to reduce the risk of cardiovascular events in these patients. In this review, platelet abnormalities are summarized together with an update of benefits and limitations of antiplatelet therapy in patients with CAD and diabetes. PMID- 26886399 TI - Decaheme Cytochrome MtrF Adsorption and Electron Transfer on Gold Surface. AB - Emergent electrical properties of multiheme cytochromes have promising applications. We performed hybrid simulations (molecular dynamics, free energy computation, and kinetic Monte Carlo) to study decaheme cytochrome, MtrF adsorption on an Au (111) surface in water and the electron transfer (ET) efficiency. Our results reveal that the gold surface's dehydration serves as a crucial driving force for protein adsorption due to large surface tension. The most possible adsorption orientation is with the ET terminal (heme5) approaching the gold surface, which yields a pathway for ET between the substrate and the aqueous environment. Upon adsorption, protein's secondary structures and central domains (II and IV) bonded with heme-residues remain relatively stable. MtrF surface mobility is dictated by thiol-gold interaction and strong binding between Au(111) and peptide aromatic groups. ET transfer rate across protein heme-network along the solvent-to-surface direction is slightly larger than that of the reverse direction, but lower than that of the solvation structure. PMID- 26886400 TI - How gender-expectancy affects the processing of "them". AB - How sensitive is pronoun processing to expectancies based on real-world knowledge and language usage? The current study links research on the integration of gender stereotypes and number-mismatch to explore this question. It focuses on the use of them to refer to antecedents of different levels of gender-expectancy (low cyclist, high-mechanic, known-spokeswoman). In a rating task, them is considered increasingly unnatural with greater gender-expectancy. However, participants might not be able to differentiate high-expectancy and gender-known antecedents online because they initially search for plural antecedents (e.g., Sanford & Filik), and they make all-or-nothing gender inferences. An eye-tracking study reveals early differences in the processing of them with antecedents of high gender-expectancy compared with gender-known antecedents. This suggests that participants have rapid access to the expected gender of the antecedent and the level of that expectancy. PMID- 26886401 TI - Unrealistic Hope and Unnecessary Fear: Exploring How Sensationalistic News Stories Influence Health Behavior Motivation. AB - In light of the inherent conflict between the nature of science (slow, subject to correction) and the nature of news (immediate, dramatic, novel), this study examines the effect of emotional health news coverage on intentions to engage in protective health behaviors. One hundred seventy-seven students read news stories designed to evoke either fear or hope about human papillomavirus (HPV) followed by different levels of response efficacy information regarding an impending HPV vaccine. Results indicated no main effects for emotion frame or response efficacy, but a significant interaction suggested that emotionally-consistent presentations (fear/low efficacy; hope/high efficacy) boosted intentions to engage in protective actions relative to emotionally-inconsistent, sensationalized presentations (fear/high efficacy, hope/low efficacy). Consistent with the emotion-as-frame perspective, this effect was moderated by perceived knowledge about HPV prevention. Effects of the sensationalized story constructions on trust in health news were also evidenced. Implications for the role of emotional health news coverage in priming prior knowledge about preventative health behaviors, along with future research directions, are discussed. PMID- 26886402 TI - Generational differences in American students' reasons for going to college, 1971 2014: The rise of extrinsic motives. AB - We examined generational differences in reasons for attending college among a nationally representative sample of college students (N = 8 million) entering college between 1971-2014. We validated the items on reasons for attending college against an established measure of extrinsic and intrinsic values among college students in 2014 (n = 189). Millennials (in college 2000s-2010s) and Generation X (1980s-1990s) valued extrinsic reasons for going to college ("to make more money") more, and anti-extrinsic reasons ("to gain a general education and appreciation of ideas") less than Boomers when they were the same age in the 1960s-1970s. Extrinsic reasons for going to college were higher in years with more income inequality, college enrollment, and extrinsic values. These results mirror previous research finding generational increases in extrinsic values begun by GenX and continued by Millennials, suggesting that more recent generations are more likely to favor extrinsic values in their decision-making. PMID- 26886405 TI - Types and Characteristics of Childhood Sexual Abuse: How Do They Matter in HIV Sexual Risk Behaviors Among Women in Methadone Treatment in New York City? AB - BACKGROUND: Childhood sexual abuse (CSA) is often considered an important distal factor in HIV sexual risk behaviors; however, there are limited and mixed findings regarding this relationship among women experiencing substance use problems. In addition, research with this population of women has yet to examine differences in observed CSA-HIV sexual risk behaviors relationships by CSA type and characteristics. OBJECTIVES: This study examines relationships between CSA coding, type, and characteristics and HIV sexual risk behaviors with main intimate partners among a random sample of 390 women in methadone treatment in New York City who completed individual interviews with trained female interviewers. RESULTS: Findings from logistic regression analyses indicate that CSA predicts substance use with sexual activity, with variations by CSA coding, type, and characteristics; however, the role of CSA is more limited than expected. Having a main partner with HIV risk mediates some relationships between CSA and drinking four or more drinks prior to sex. Intimate partner violence is the most consistent predictor of sexual risk behaviors. Other salient factors include polysubstance use, depression, social support, recent incarceration, relationship characteristics, and HIV status. CONCLUSIONS/IMPORTANCE: This study contributes to understanding of relationships between CSA and HIV sexual risk behaviors and key correlates associated with HIV sexual risk behaviors among women in methadone treatment. It also highlights the complexity of measuring CSA and its association with sexual risk behaviors and the importance of comprehensive approaches to HIV prevention that address psychological, relational, situational, and substance use experiences associated with sexual risk behaviors among this population. PMID- 26886404 TI - Cost of illness and illness perceptions in patients with fibromyalgia. AB - OBJECTIVES: The disease impact and economic burden of fibromyalgia (FM) are high for patients and society at large. Knowing potential determinants of economic costs may help in reducing this burden. Cognitive appraisals (perceptions) of the illness could affect costs. The present study estimated costs of illness in FM and examined the association between these costs and illness perceptions. METHODS: Questionnaire data of FM severity (FIQ), illness perceptions (IPQ-R-FM), productivity losses (SF-HLQ) and health care use were collected in a cohort of patients with FM. Costs were calculated and dichotomised (median split). Univariate and hierarchic logistic regression models examined the unique association of each illness perception with 1) health care costs and 2) costs of productivity losses. Covariates were FM severity, comorbidity and other illness perceptions. RESULTS: 280 patients participated: 95% female, mean age 42 (SD=12) years. Annualised costs of FM per patient were ?2944 for health care, and ?5731 for productivity losses. In multivariate analyses, a higher disease impact (FIQ) and two of seven illness perceptions (IPQ-R-FM) were associated with high health care costs: 1) high scores on 'cyclical timeline' reflecting a fluctuating, unpredictable course and 2) low scores on 'emotional representations', thus not perceiving a connection between fibromyalgia and emotions. None of the variables was associated with productivity losses. CONCLUSIONS: Our study indicates that perceiving a fluctuating course and low emotional representation, which perhaps reflects somatic fixation, are associated with health care costs in FM. Future studies should examine whether targeting these illness perceptions results in reduction of costs. PMID- 26886408 TI - Kinetic Diversity of Striatal Dopamine: Evidence from a Novel Protocol for Voltammetry. AB - In vivo voltammetry reveals substantial diversity of dopamine kinetics in the rat striatum. To substantiate this kinetic diversity, we evaluate the temporal distortion of dopamine measurements arising from the diffusion-limited adsorption of dopamine to voltammetric microelectrodes. We validate two mathematical procedures for correcting adsorptive distortion, both of which substantiate that dopamine's apparent kinetic diversity is not an adsorption artifact. PMID- 26886407 TI - Metal (Ag, Cd, Cu, Ni, Tl, and Zn) Binding to Cytosolic Biomolecules in Field Collected Larvae of the Insect Chaoborus. AB - We characterized the biomolecules involved in handling cytosolic metals in larvae of the phantom midge (Chaoborus) collected from five mining-impacted lakes by determining the distribution of Ag, Cd, Cu, Ni, Tl, and Zn among pools of various molecular weights (HMW: high molecular weight, >670-40 kDa; MMW: medium molecular weight, 40-<1.3 kDa; LMW: low molecular weight, <1.3 kDa). Appreciable concentrations of nonessential metals were found in the potentially metal sensitive HMW (Ag and Ni) and LMW (Tl) pools, whereas the MMW pool, which includes metallothioneins (MTs) and metallothionein-like proteins and peptides (MTLPs), appears to be involved in Ag and Cd detoxification. Higher-resolution fractionation of the heat-stable protein (HSP) fraction revealed further differences in the partitioning of nonessential metals (i.e., Ag = Cd ? Ni ? Tl). These results provide unprecedented details about the metal-handling strategies employed by a metal-tolerant, freshwater animal in a field situation. PMID- 26886409 TI - Neutrophil-Lymphocyte Ratio Predicts Survival in Terminal Cancer Patients. AB - BACKGROUND: Neutrophil-lymphocyte count ratio (NLR) is a prognostic factor in cancer, although its prognostic significance in terminally ill cancer patients is not clear. OBJECTIVE: We investigated the association of NLR with survival in patients with terminal cancer. METHODS: We retrospectively investigated 205 consecutive patients with terminal cancer admitted to a palliative care unit during 2014. RESULTS: The median value of NLR was 9.7. In univariable analysis, NLR of 10 or more was significantly associated with shorter survival and NLR further discriminated survival of each palliative prognostic index (PPI) group. In multivariable analysis, increased NLR (>=10) was associated with shorter survival (hazards ratio [HR] 1.54, p<0.005), along with poor performance status (HR 1.55, p < 0.011), high PPI score (HR 1.59, p<0.003), and hyperbilirubinemia (HR 1.84, p < 0.001). CONCLUSION: Our results suggest that elevated NLR was an independent prognostic factor for poor survival in patients with terminal cancer. PMID- 26886410 TI - Successful treatment of rapidly progressing severe fever with thrombocytopenia syndrome with neurological complications using intravenous immunoglobulin and corticosteroid. AB - Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in China, diagnostic methods have evolved. Despite definitive diagnoses, SFTS management has focused on prevention and supportive care. Although conservative treatment is effective for mild cases, there is an urgent need for an effective therapeutic modality to treat severe cases because of the high mortality associated with these. In this study, we report two cases of SFTS with neurological manifestations that fully recovered after a combination treatment consisting of intravenous immunoglobulin and corticosteroid. PMID- 26886406 TI - National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers. AB - BACKGROUND: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. CONCLUSIONS: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet. PMID- 26886412 TI - Methylotroph Infections and Chronic Granulomatous Disease. AB - Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis. PMID- 26886413 TI - Cyclic Peptide-Decorated Self-Assembled Nanohybrids for Selective Recognition and Detection of Multivalent RNAs. AB - Although there has been substantial advancement in the development of nanostructures, the development of self-assembled nanostructures that can selectively recognize multivalent targets has been very difficult. Here we show the proof of concept that topology-controlled peptide nanoassemblies can selectively recognize and detect a multivalent RNA target. We compared the differential behaviors of peptides in a linear or cyclic topology in terms of peptide-gold nanoparticle hybrid nanostructure formation, conformational stabilization, monovalent and multivalent RNA binding in vitro, and multivalent RNA recognition in live cells. When the topology-dependent selectivity amplification of the cyclic peptide hybrids is combined with the noninvasive nature of dark-field microscopy, the cellular localization of the viral Rev response element (RRE) RNA can be monitored in situ. Because intracellular interactions are often mediated by overlapping binding partners with weak affinity, the topology-controlled peptide assemblies can provide a versatile means to convert weak ligands into multivalent ligands with high affinity and selectivity. PMID- 26886411 TI - Genome-Wide Comparative Analysis of Chemosensory Gene Families in Five Tsetse Fly Species. AB - For decades, odour-baited traps have been used for control of tsetse flies (Diptera; Glossinidae), vectors of African trypanosomes. However, differential responses to known attractants have been reported in different Glossina species, hindering establishment of a universal vector control tool. Availability of full genome sequences of five Glossina species offers an opportunity to compare their chemosensory repertoire and enhance our understanding of their biology in relation to chemosensation. Here, we identified and annotated the major chemosensory gene families in Glossina. We identified a total of 118, 115, 124, and 123 chemosensory genes in Glossina austeni, G. brevipalpis, G. f. fuscipes, G. pallidipes, respectively, relative to 127 reported in G. m. morsitans. Our results show that tsetse fly genomes have fewer chemosensory genes when compared to other dipterans such as Musca domestica (n>393), Drosophila melanogaster (n = 246) and Anopheles gambiae (n>247). We also found that Glossina chemosensory genes are dispersed across distantly located scaffolds in their respective genomes, in contrast to other insects like D. melanogaster whose genes occur in clusters. Further, Glossina appears to be devoid of sugar receptors and to have expanded CO2 associated receptors, potentially reflecting Glossina's obligate hematophagy and the need to detect hosts that may be out of sight. We also identified, in all species, homologs of Ir84a; a Drosophila-specific ionotropic receptor that promotes male courtship suggesting that this is a conserved trait in tsetse flies. Notably, our selection analysis revealed that a total of four gene loci (Gr21a, GluRIIA, Gr28b, and Obp83a) were under positive selection, which confers fitness advantage to species. These findings provide a platform for studies to further define the language of communication of tsetse with their environment, and influence development of novel approaches for control. PMID- 26886414 TI - TAFRO syndrome successfully treated with tocilizumab: A case report and systematic review. AB - Thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome is considered as a unique clinicopathologic variant of multicentric Castleman's disease and is recently reported in Japan. This entity represents a severe inflammatory state leading to organ failures such as severe liver dysfunction seen in our case, and can be treated by immunosuppressive agents, steroids, and cyclosporine shown in several case reports. A systematic review and our case suggest the potential utility of tocilizumab as a treatment for TAFRO syndrome. PMID- 26886415 TI - Emotional, physical and financial burdens of stigma against people living with HIV/AIDS in China. AB - Numerous researches have shown pernicious effects of stigma against people living with HIV/AIDS (PLWHA). However, no available studies have reported these negative effects including emotional, physical to financial burdens to PLWHA. In the current study, we aim to explore different types of stigma (e.g., perceived, internalized and enacted) and the relevant consequences among PLWHA in China. A cross-sectional study was conducted from 2012 to 2013 in the Guangxi Autonomous Region in China. The validated Berger HIV Stigma Scale was used to measure various types of stigma. We employed a series of linear, logistic and polytomous regression models to assess the association between stigma and different consequences while accounting for potential confounders for each specific model. Of the total sample, 2987 PLWHA provided valid responses with 63% being male and having an average age of 42.9 years. Perceived, internalized and enacted HIV stigma were prevalent among participants, and resulted in various burdens with different magnitudes in their life contexts. Specially, PLWHA who reported higher perceived and internalized stigma were more likely to be imposed on emotional and physical burdens (p < .05). People who reported higher enacted stigma had heavier financial burden compared to their peers (p < .05). Our findings revealed that devastating consequences of HIV-related stigma in China. The prevalent stigmatizing attitudes have pushed PLWHA to the fringes of society and affected them at multiple aspects in their life context. We call for tailored efforts to overcome stigma and discrimination against PLWHA. PMID- 26886416 TI - Shape Ontogeny of the Distal Femur in the Hominidae with Implications for the Evolution of Bipedality. AB - Heterochrony has been invoked to explain differences in the morphology of modern humans as compared to other great apes. The distal femur is one area where heterochrony has been hypothesized to explain morphological differentiation among Plio-Pleistocene hominins. This hypothesis is evaluated here using geometric morphometric data to describe the ontogenetic shape trajectories of extant hominine distal femora and place Plio-Pleistocene hominins within that context. Results of multivariate statistical analyses showed that in both Homo and Gorilla, the shape of the distal femur changes significantly over the course of development, whereas that of Pan changes very little. Development of the distal femur of Homo is characterized by an elongation of the condyles, and a greater degree of enlargement of the medial condyle relative to the lateral condyle, whereas Gorilla are characterized by a greater degree of enlargement of the lateral condyle, relative to the medial. Early Homo and Australopithecus africanus fossils fell on the modern human ontogenetic shape trajectory and were most similar to either adult or adolescent modern humans while specimens of Australopithecus afarensis were more similar to Gorilla/Pan. These results indicate that shape differences among the distal femora of Plio-Pleistocene hominins and humans cannot be accounted for by heterochrony alone; heterochrony could explain a transition from the distal femoral shape of early Homo/A. africanus to modern Homo, but not a transition from A. afarensis to Homo. That change could be the result of genetic or epigenetic factors. PMID- 26886417 TI - Insulin Resistance and a Long, Strange Trip. PMID- 26886420 TI - Recent Advances in Electrocatalysts for Oxygen Reduction Reaction. AB - The recent advances in electrocatalysis for oxygen reduction reaction (ORR) for proton exchange membrane fuel cells (PEMFCs) are thoroughly reviewed. This comprehensive Review focuses on the low- and non-platinum electrocatalysts including advanced platinum alloys, core-shell structures, palladium-based catalysts, metal oxides and chalcogenides, carbon-based non-noble metal catalysts, and metal-free catalysts. The recent development of ORR electrocatalysts with novel structures and compositions is highlighted. The understandings of the correlation between the activity and the shape, size, composition, and synthesis method are summarized. For the carbon-based materials, their performance and stability in fuel cells and comparisons with those of platinum are documented. The research directions as well as perspectives on the further development of more active and less expensive electrocatalysts are provided. PMID- 26886421 TI - Sentinel lymph node biopsy in breast cancer: a technical and clinical appraisal. AB - Breast cancer is the most common type of cancer diagnosed in women worldwide. Regional lymph node status is one of the strongest predictors of long-term prognosis in primary breast cancer. Sentinel lymph node biopsy (SLNB) has replaced axillary lymph node dissection as the standard surgical procedure for staging clinically tumor-free regional nodes in patients with early-stage breast cancer. SLNB staging considerably reduces surgical morbidity in terms of shoulder dysfunction and lymphedema, without affecting diagnostic accuracy and prognostic information. Clinicians should not recommend axillary lymph node dissection for women with early-stage breast cancer who have tumor-free findings on SLNB because there is no advantage in terms of overall survival and disease-free survival. Starting from the early 1990s, SLNB has increasingly been used in breast cancer management, but its role is still debated under many clinical circumstances. Moreover, there is still a lack of standardization of the basic technical details of the procedure that is likely to be responsible for the variability found in the false-negative rate of the procedure (5.5-16.7%). In this article, we report the aspects of SLNB that are well established, those that are still debated, and the advancements that have taken place over the last 20 years. We have provided an update on the methodology from both a technical and a clinical point of view in the light of the most recent publications. PMID- 26886419 TI - Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. AB - BACKGROUND: Previous clinical trials have suggested that carotid-artery stenting with a device to capture and remove emboli ("embolic protection") is an effective alternative to carotid endarterectomy in patients at average or high risk for surgical complications. METHODS: In this trial, we compared carotid-artery stenting with embolic protection and carotid endarterectomy in patients 79 years of age or younger who had severe carotid stenosis and were asymptomatic (i.e., had not had a stroke, transient ischemic attack, or amaurosis fugax in the 180 days before enrollment) and were not considered to be at high risk for surgical complications. The trial was designed to enroll 1658 patients but was halted early, after 1453 patients underwent randomization, because of slow enrollment. Patients were followed for up to 5 years. The primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points. RESULTS: Stenting was noninferior to endarterectomy with regard to the primary composite end point (event rate, 3.8% and 3.4%, respectively; P=0.01 for noninferiority). The rate of stroke or death within 30 days was 2.9% in the stenting group and 1.7% in the endarterectomy group (P=0.33). From 30 days to 5 years after the procedure, the rate of freedom from ipsilateral stroke was 97.8% in the stenting group and 97.3% in the endarterectomy group (P=0.51), and the overall survival rates were 87.1% and 89.4%, respectively (P=0.21). The cumulative 5-year rate of stroke-free survival was 93.1% in the stenting group and 94.7% in the endarterectomy group (P=0.44). CONCLUSIONS: In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was noninferior to endarterectomy with regard to the rate of the primary composite end point at 1 year. In analyses that included up to 5 years of follow-up, there were no significant differences between the study groups in the rates of non procedure-related stroke, all stroke, and survival. (Funded by Abbott Vascular; ACT I ClinicalTrials.gov number, NCT00106938.). PMID- 26886424 TI - Unicameral Bone Cyst of the Medial Cuneiform: A Case Report. AB - A unicameral bone cyst is a relatively uncommon, benign bone tumor found in the metaphysis of long bones, such as the humerus and the femur, in skeletally immature persons. In the foot, these benign, fluid-filled cavities are most commonly found within the os calcis. We present a case report of a 10-year-old female with a unicameral bone cyst of the medial cuneiform. PMID- 26886423 TI - In Vivo versus Augmented Reality Exposure in the Treatment of Small Animal Phobia: A Randomized Controlled Trial. AB - Although in vivo exposure is the treatment of choice for specific phobias, some acceptability problems have been associated with it. Virtual Reality exposure has been shown to be as effective as in vivo exposure, and it is widely accepted for the treatment of specific phobias, but only preliminary data are available in the literature about the efficacy of Augmented Reality. The purpose of the present study was to examine the efficacy and acceptance of two treatment conditions for specific phobias in which the exposure component was applied in different ways: In vivo exposure (N = 31) versus an Augmented Reality system (N = 32) in a randomized controlled trial. "One-session treatment" guidelines were followed. Participants in the Augmented Reality condition significantly improved on all the outcome measures at post-treatment and follow-ups. When the two treatment conditions were compared, some differences were found at post-treatment, favoring the participants who received in vivo exposure. However, these differences disappeared at the 3- and 6-month follow-ups. Regarding participants' expectations and satisfaction with the treatment, very positive ratings were reported in both conditions. In addition, participants from in vivo exposure condition considered the treatment more useful for their problem whereas participants from Augmented Reality exposure considered the treatment less aversive. Results obtained in this study indicate that Augmented Reality exposure is an effective treatment for specific phobias and well accepted by the participants. PMID- 26886425 TI - Metals, Parasites, and Environmental Conditions Affecting Breeding Populations of Spotted Salamanders (Ambystoma maculatum) in Northern Arkansas, USA. AB - The spotted salamander (Ambystoma maculatum) is indigenous to northern Arkansas, and several breeding sites are known to exist in the region. Spotted salamanders (n = 17) were collected and examined for parasites and only three females harbored nematodes (Physaloptera spp.). Chronic aquatic bioassays were conducted using water collected from eight breeding ponds during different hydroperiod events. No lethal or sublethal effects were measured in Ceriodaphnia dubia; however, decreased growth and survival were seen in Pimephales promelas. Aqueous, sediment, and salamander hepatic samples were analyzed for As, Cd, Cu, Pb, and Ni. Metal analysis revealed possible increased metal exposure following precipitation, with greatest metal concentrations measured in sediment samples. Hepatic metal concentrations were similar in parasitized and non-parasitized individuals, and greatest Pb concentrations were measured following normal precipitation events. Determining environmental stressors of amphibians, especially during their breeding and subsequent larval life stage, is imperative to improve species conservation. PMID- 26886422 TI - CDK13, a Kinase Involved in Pre-mRNA Splicing, Is a Component of the Perinucleolar Compartment. AB - The perinucleolar compartment (PNC) is a subnuclear stucture forming predominantly in cancer cells; its prevalence positively correlates with metastatic capacity. Although several RNA-binding proteins have been characterized in PNC, the molecular function of this compartment remains unclear. Here we demonstrate that the cyclin-dependent kinase 13 (CDK13) is a newly identified constituent of PNC. CDK13 is a kinase involved in the regulation of gene expression and whose overexpression was found to alter pre-mRNA processing. In this study we show that CDK13 is enriched in PNC and co-localizes all along the cell cycle with the PNC component PTB. In contrast, neither the cyclins K and L, known to associate with CDK13, nor the potential kinase substrates accumulate in PNC. We further show that CDK13 overexpression increases PNC prevalence suggesting that CDK13 may be determinant for PNC formation. This result linked to the finding that CDK13 gene is amplified in different types of cancer indicate that this kinase can contribute to cancer development in human. PMID- 26886427 TI - Estimation of Heavy Metal Contamination in Groundwater and Development of a Heavy Metal Pollution Index by Using GIS Technique. AB - Heavy metal (Al, As, Ba, Cr, Cu, Fe, Mn, Ni, Se and Zn) concentration in sixty six groundwater samples of the West Bokaro coalfield were analyzed using inductively coupled plasma-mass spectroscopy for determination of seasonal fluctuation, source apportionment and heavy metal pollution index (HPI). Metal concentrations were found higher in the pre-monsoon season as compared to the post-monsoon season. Geographic information system (GIS) tool was attributed to study the metals risk in groundwater of the West Bokaro coalfield. The results show that 94 % of water samples were found as low class and 6 % of water samples were in medium class in the post-monsoon season. However, 79 % of water samples were found in low class, 18 % in medium class and 3 % in high class in the pre monsoon season. The HPI values were below the critical pollution index value of 100. The concentrations of Al, Fe, Mn, and Ni are exceeding the desirable limits in many groundwater samples in both seasons. PMID- 26886426 TI - Monitoring of Lead (Pb) Pollution in Soils and Plants Irrigated with Untreated Sewage Water in Some Industrialized Cities of Punjab, India. AB - Soil and plant samples were collected from sewage and tubewell irrigated sites from three industrially different cities of Punjab (India) viz. Ludhiana, Jalandhar and Malerkotla. The extent of lead (Pb) pollution was assessed with respect to background concentration of tubewell irrigation. In sewage irrigated surface soil layer (0-15 cm), the extent of Pb accumulation was 4.61, 4.20 and 2.26 times higher than those receiving tubewell irrigation sites in Ludhiana, Jalandhar and Malerkotla, respectively. Multiple regression analysis showed that soil pH, organic carbon, calcium carbonate and clay were significant soil parameters explaining the variation in available soil Pb. The mean Pb content in plants receiving sewage irrigation was 4.56, 5.48 and 2.72 times higher than tubewell irrigation in Ludhiana, Jalandhar and Malerkotla, respectively. The content of Pb in plants receiving sewage irrigation revealed that, assuming a weekly consumption of 500-1000 g of vegetables grown on sewage irrigated soils by an adult of 70 kg body weight, the Pb intake may far exceed the World Health Organization proposed tolerable weekly intake of Pb. PMID- 26886428 TI - Effects of Maternally-Transferred Methylmercury on Stress Physiology in Northern Water Snake (Nerodia sipedon) Neonates. AB - Biomagnification of methylmercury in aquatic systems can cause elevated tissue mercury (Hg) and physiological stress in top predators. Mercury is known to affect stress hormone levels in mammals, birds and fish. In this study, the effects of maternally-transferred methylmercury on the stress physiology of Northern Water Snake (Nerodia sipedon) neonates were tested. Gravid females were dosed via force-fed capsules during late gestation with 0, 0.01, or 10 ug methylmercury per gram of body mass. Plasma corticosterone levels and leukocyte differentials were analyzed in baseline and confinement-stressed neonates from all dose levels. Neither Hg nor confinement stress had a significant effect on leukocyte differentials nor was Hg related to corticosterone levels. However, stress group neonates showed lower heterophil/lymphocyte ratios and this study was the first to show that neonate N. sipedon can upregulate CORT in response to stress. These results indicate that N. sipedon may be somewhat tolerant to Hg contamination. PMID- 26886429 TI - Micronutrient Fractionation in Coal Mine-Affected Agricultural Soils, India. AB - Assessment of the anthropogenic impacts on bioavailability, mobility, immobility and toxicity of four micronutrients (Cu, Fe, Mn, and Zn) were carried out by Community Bureau of Reference (BCR) fractionation scheme in agricultural soils (n = 10) around Jharia coalfield, eastern India. The relative abundance of micronutrients was as follows: Fe > Mn > Zn > Cu. The enrichment factor was >1 for Zn (6.1) and Cu (1.8) near coal mining area indicated toward soil pollution due to coal mining activities and application of inorganic fertilizers. The I geo values of micronutrients were <0 suggest no pollution with respect to Cu, Fe, Mn and Zn. Correlation analysis showed geogenic origin of soil micronutrients and derived mainly from weathering of minerals present in the parent rock. The mean values of Cu, Mn and Zn were less than certified reference material indicating highly leached agricultural soils in the study region. BCR fractionation of micronutrients showed that a single element could not reveal all types of chemical reactions occurring in soil consortium. PMID- 26886432 TI - Comparative Study of MIL-96(Al) as Continuous Metal-Organic Frameworks Layer and Mixed-Matrix Membrane. AB - MIL-96(Al) layers were prepared as supported metal-organic frameworks membrane via reactive seeding using the alpha-alumina support as the Al source for the formation of the MIL-96(Al) seeds. Depending on the solvent mixture employed during seed formation, two different crystal morphologies, with different orientation of the transport-active channels, have been formed. This crystal orientation and habit is predefined by the seed crystals and is kept in the subsequent growth of the seeds to continuous layers. In the gas separation of an equimolar H2/CO2 mixture, the hydrogen permeability of the two supported MIL 96(Al) layers was found to be highly dependent on the crystal morphology and the accompanied channel orientation in the layer. In addition to the neat supported MIL-96(Al) membrane layers, mixed-matrix membranes (MMMs, 10 wt % filler loading) as a composite of MIL-96(Al) particles as filler in a continuous Matrimid polymer phase have been prepared. Five particle sizes of MIL-96(Al) between 3.2 MUm and 55 nm were synthesized. In the preparation of the MIL-96(Al)/Matrimid MMM (10 wt % filler loading), the following preparation problems have been identified: The bigger micrometer-sized MIL-96(Al) crystals show a trend toward sedimentation during casting of the MMM, whereas for nanoparticles aggregation and recrystallization to micrometer-sized MIL-96(Al) crystals has been observed. Because of these preparation problems for MMM, the neat supported MIL-96(Al) layers show a relatively high H2/CO2 selectivity (~9) and a hydrogen permeance approximately 2 magnitudes higher than that of the best MMM. PMID- 26886431 TI - Non-Oxygenated Sesquiterpenes in the Essential Oil of Copaifera langsdorffii Desf. Increase during the Day in the Dry Season. AB - The present study aimed to evaluate the effect of seasonal and diurnal events on the chemical profile of the essential oil obtained from the leaves of Copaifera langsdorffii Desf. This study was performed in a Brazilian savanna named Cerrado. We identified the best harvesting period for obtaining the highest amount of compounds used for commercial and industrial purposes. The chemical profile of the essential oils was evaluated by GC-FID and GC-MS, and the results were assessed through multivariate analyses. The data showed that the time of day and seasonal variations affect the quality of the essential oil obtained. Leaves harvested at the end of the day (5:00 pm) in the dry season resulted in richer essential oils with higher amounts of non-oxygenated sesquiterpenes. To the best of our knowledge, environmental conditions induce metabolic responses in the leaves of C. langsdorffii, which changes the patterns of sesquiterpene production. Therefore, these factors need to be considered to obtain better concentrations of bioactive compounds for pharmacological studies. PMID- 26886433 TI - Patient-provider communication with HIV-positive women about abnormal Pap test results. AB - In this article, the authors examine communication between women living with human immunodeficiency virus (WLH) and health care providers (HCPs) regarding abnormal Pap tests. During the period of March 2011 through April 2012, 145 WLH were recruited from Ryan White funded clinics and community-based AIDS service organizations located in the southeastern United States. WLH who had an abnormal Pap test (69%, n = 100/145) were asked if their HCP shared and explained information about abnormal Pap tests. The authors performed chi-square tests and multivariable logistic regression analyses using Stata I/C 13. HCPs shared information about abnormal Pap tests with 60% of participants, and explained the information they shared to 78% of those. Health literate participants were more than three times as likely to have read the information received about abnormal Pap tests (adjusted odds ratio [aOR] = 3.49, 95% confidence interval [CI] 1.19 10.23), and almost five times as likely to have understood the cancer information they read (aOR = 4.70, 95% CI 1.55-14.24). Knowing other women who had had an abnormal Pap test was not significantly associated with cancer information seeking or processing after controlling for confounding factors. The present findings underscore the need to increase WLH's health literacy as an intermediate step to improving patient-provider communication among WLH. Lay sources of cancer information for WLH warrant further study. PMID- 26886435 TI - Encapsulated or Not Encapsulated? Ammonium Salts Can Be Encapsulated in Hexameric Capsules of Pyrogallol[4]arene. AB - Tetraalkylammonium salts were found, contrary to literature reports, to be encapsulated into hexameric capsules of pyrogallol[4]arene in benzene solution. The guest affinity depended on the length of the alkyl chain, the counteranion, the solvent used, the ammonium concentration, and most importantly, the pyrogallol[4]arene to ammonium salt ratio. At high ammonium salt to pyrogallol[4]arene ratios no encapsulation was observed, presumably since the high salt destabilized the formed hexamers. PMID- 26886430 TI - Tetra-O-Methyl Nordihydroguaiaretic Acid Broadly Suppresses Cancer Metabolism and Synergistically Induces Strong Anticancer Activity in Combination with Etoposide, Rapamycin and UCN-01. AB - The ability of Tetra-O-methyl nordihydroguaiaretic acid (M4N) to induce rapid cell death in combination with Etoposide, Rapamycin, or UCN-01 was examined in LNCaP cells, both in cell culture and animal experiments. Mice treated with M4N drug combinations with either Etoposide or Rapamycin showed no evidence of tumor and had a 100% survival rate 100 days after tumor implantation. By comparison all other vehicles or single drug treated mice failed to survive longer than 30 days after implantation. This synergistic improvement of anticancer effect was also confirmed in more than 20 cancer cell lines. In LNCaP cells, M4N was found to reduce cellular ATP content, and suppress NDUFS1 expression while inducing hyperpolarization of mitochondrial membrane potential. M4N-treated cells lacked autophagy with reduced expression of BNIP3 and ATG5. To understand the mechanisms of this anticancer activity of M4N, the effect of this drug on three cancer cell lines (LNCaP, AsPC-1, and L428 cells) was further examined via transcriptome and metabolomics analyses. Metabolomic results showed that there were reductions of 26 metabolites essential for energy generation and/or production of cellular components in common with these three cell lines following 8 hours of M4N treatment. Deep RNA sequencing analysis demonstrated that there were sixteen genes whose expressions were found to be modulated following 6 hours of M4N treatment similarly in these three cell lines. Six out of these 16 genes were functionally related to the 26 metabolites described above. One of these up regulated genes encodes for CHAC1, a key enzyme affecting the stress pathways through its degradation of glutathione. In fact M4N was found to suppress glutathione content and induce reactive oxygen species production. The data overall indicate that M4N has profound specific negative impacts on a wide range of cancer metabolisms supporting the use of M4N combination for cancer treatments. PMID- 26886437 TI - An Anion Metal-Organic Framework with Lewis Basic Sites-Rich toward Charge Exclusive Cationic Dyes Separation and Size-Selective Catalytic Reaction. AB - Organic dye pollutants become a big headache due to their toxic nature to the environment, and it should be one of the best solutions if we can separate and reuse them. Here, we report the synthesis and characterization of a microporous anion metal-organic framework (MOF) with Lewis basic sites-rich based on TDPAT (2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine) ligand, FJI-C2, which shows high adsorption and separation of cationic dye based on the charge exclusive effect. Compared to other MOF materials, FJI-C2 shows the largest adsorption amount of methylene blue (1323 mg/g) at room temperature due to the nature of the anion frameworks and high surface area/pore volume. Furthermore, motivated by the adsorption properties of large guest molecules, we proceeded to investigate the catalytic behaviors of FJI-C2, not only because the large pore facilitates the mass transfer of guest molecules but also because the high density of Lewis basic sites can act as effective catalytic sites. As expected, FJI-C2 exhibits excellent catalytic performance for size-selective Knoevenagel condensation under mild conditions and can be reused several times without a significant decrease of the activity. PMID- 26886434 TI - Reproductive biology of an Alpic paleo-endemic in a changing climate. AB - Climate change is known to have a profound influence on plant reproduction, mainly because it affects plant/pollinator interactions, sometimes driving plants to extinction. Starting from the Neogene, the European climate was subjected to severe alterations. Nevertheless, several genera, including Berardia, survived these climatic changes. Despite the numerous studies performed about the relationship between climate change and plant reproductive biology, equivalent studies on ancient species are lacking, even though they may furnish crucial information on the strategies that allowed them to survive drastic climatic fluctuations. We investigated floral and reproductive features in Berardia subacaulis (Asteraceae), describing pollen vectors, capitulum and florets phenology, evaluating reproductive efficiency and defining the reproductive mode of the plant with bagging experiments and test of apomixis. B. subacaulis grows in habitats with low pollination services; it is self-compatible, but many typical features favouring cross-pollination are still present: florets are characterized by incomplete protandry, capitulum protogyny and high pollen-ovule ratio. The plant is not apomictic and self-fertilization is allowed within each capitulum. Similarly to other European Alpine endemics supposed to belong to the Mediterranean ancient tropical flora, the reproductive mode observed in the monospecific genus Berardia assured reproduction also under a pollinator decline. Differently from the other endemics, it took advantage of its spontaneous self pollination and compatibility and its generalist pollination service, common both among high altitude plants and in the Asteraceae. PMID- 26886439 TI - Rates of Cancers and Opportunistic Infections in Patients With Psoriatic Arthritis Compared With Patients Without Psoriatic Arthritis. AB - OBJECTIVES: This study aimed to estimate rates of cancer or opportunistic infection in patients with psoriatic arthritis (PsA) compared with patients without PsA. METHODS: Using the Clinical Practice Research Datalink, we conducted a cohort study of patients with a PsA diagnosis and patients without such diagnosis, matched on age, sex, general practice, and calendar time, to assess the incidence of cancers (solid, hematologic, and nonmelanoma skin cancer) and opportunistic infections. We estimated incidence rates (IRs) and IR ratios (IRRs) with 95% confidence intervals (CIs) for each outcome and stratified results in the PsA cohort by receipt of systemic PsA drugs. RESULTS: The rate of hematologic cancer was slightly higher in the PsA cohort compared with the non-PsA cohort (IRR, 1.52; 95% CI, 1.10-2.10), whereas the rates of solid cancer and of nonmelanoma skin cancer were similar between the PsA and non-PsA cohorts (IRR, 1.01; 95% CI, 0.90-1.13; and IRR, 0.97; 95% CI, 0.82-1.14, respectively). Incidence rates were higher for PsA patients who received prescriptions for PsA drugs compared with those who did not. The IRs for infection were higher in the PsA compared with the non-PsA cohort (IRR, 1.39; 95% CI, 1.31-1.47) and were significantly higher in patients who received prescriptions (IRR, 1.71; 95% CI, 1.52-1.91). CONCLUSIONS: The rates of solid and nonmelanoma skin cancers were similar in patients with PsA compared with patients without PsA, but the rates of hematologic cancer and opportunistic infections were higher in patients with PsA. In patients with PsA, rates of all outcomes were higher among those who received prescriptions for systemic PsA therapy. PMID- 26886438 TI - Direct Comparative Effectiveness Among 3 Anti-Tumor Necrosis Factor Biologics in a Real-Life Cohort of Patients With Rheumatoid Arthritis. AB - OBJECTIVE: This study aimed to compare the clinical response at 36 months and evaluate the adverse events in a cohort of patients with rheumatoid arthritis treated with etanercept, infliximab, or adalimumab. METHODS: An observational retrospective cohort study was performed. Patients older than 18 years with active rheumatoid arthritis, for which the physician had initiated a treatment scheme with etanercept, infliximab, or adalimumab, were included in the study. The follow-up was conducted through at least trimestral evaluations during the course of 36 months. Outcomes evaluated included Disease Activity Score 28, level of disease activity, Health Assessment Questionnaire, and degree of disability. RESULTS: Three hundred seven subjects were included in the cohort (108 adalimumab, 107 infliximab, and 92 etanercept). The median Disease Activity Score 28 at the onset was 4.1 and 2.39 at month 36. There were no differences among the 3 medications (P = 0.51). The remission rate was of 7.4 per 100 people per month (95% confidence interval [CI], 6.6-8.3) without differences between groups. The initial Health Assessment Questionnaire median was 1.75 and 0.25 at 36 months. No differences per medicine were found (P = 0.54). The most common adverse effect was dermatitis. Eighteen cases of serious adverse effects occurred, including 11 cases of serious infectious events. The adverse events rates were as follows: infliximab, 24 per 100 people per year (95% CI, 19-29); adalimumab, 22 per 100 people per year (95% CI, 18-27); and etanercept, 12 per 100 people per year (95% CI, 8-16). CONCLUSIONS: Etanercept, infliximab, and adalimumab are 3 effective therapeutic anti-tumor necrosis factor alternatives to reduce the level of severity and the degree of disability generated by rheumatoid arthritis. Etanercept presented a rate of adverse events lower than those for infliximab and adalimumab. PMID- 26886440 TI - A Network Meta-analysis Comparing Exenatide Once Weekly with Other GLP-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus. AB - INTRODUCTION: Exenatide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA), approved for treatment of type 2 diabetes mellitus (T2DM). There is limited direct evidence comparing the efficacy and tolerability of exenatide 2 mg once weekly (QW) to other GLP-1 RAs. A network meta-analysis (NMA) was conducted to estimate the relative efficacy and tolerability of exenatide QW versus other GLP 1 RAs for the treatment of adults with T2DM inadequately controlled on metformin monotherapy. METHODS: A systematic literature review was conducted to identify randomized controlled trials (RCTs) that investigated GLP-1 RAs (albiglutide, dulaglutide, exenatide, liraglutide, and lixisenatide) at approved doses in the United States/Europe, added on to metformin only and of 24 +/- 6 weeks treatment duration. A Bayesian NMA was conducted. RESULTS: Fourteen RCTs were included in the NMA. Exenatide QW obtained a statistically significant reduction in glycated hemoglobin (HbA1c) relative to lixisenatide 20 ug once daily. No other comparisons of exenatide QW to other GLP-1 RAs were statistically significant for change in HbA1c. No statistically significant differences in change in weight, systolic blood pressure, risk of nausea or discontinuation due to adverse events were observed for exenatide QW versus other GLP-1 RAs. CONCLUSION: Exenatide QW demonstrated similar effectiveness and tolerability compared to other GLP-1 RAs, for the treatment of T2DM in adults inadequately controlled on metformin alone. PMID- 26886442 TI - AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease. AB - Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, lorazepam, and buspirone in an elevated plus-maze model, elevated platform, and open field tests. The compound demonstrated low toxicity and no side effects in vivo, an appropriate pharmacokinetic profile, and stability. In conclusion, AVN-211 significantly delayed or partially halted the progressive decline in memory function associated with AD, which makes it an interesting drug candidate for the treatment of neurodegenerative and psychiatric disorders. Advanced clinical trials are currently under active discussion and in high priority. PMID- 26886441 TI - Hypoglycemia Event Rates: A Comparison Between Real-World Data and Randomized Controlled Trial Populations in Insulin-Treated Diabetes. AB - INTRODUCTION: Hypoglycemia is the most common adverse effect of diabetes therapy, particularly insulin treatment. Hypoglycemia is associated with considerable clinical and economic burden, and may be under-reported. The aim of this study was to com pare the frequency of hypoglycemic events reported in real-world settings with those reported in clinical trials. METHODS: We conducted a structured literature review in PubMed to identify hypoglycemic event rates in patients with type 1 diabetes mellitus (T1DM) and insulin-treated type 2 diabetes mellitus (T2DM) from real-world data (RWD) and randomized controlled trials (RCTs). The search was restricted to English language, full-text publications from 2010 onwards, reporting on treatment of T1DM or T2DM with basal only, basal bolus, or premix insulin. RESULTS: The final dataset included 30 studies (11 RWD studies and 19 RCTs). Six studies (RWD, n = 2; RCT, n = 4) reported hypoglycemia event rates in people with T1DM. For all reported categories of hypoglycemia (severe, non-severe, and nocturnal), rates were consistently higher in RWD studies compared with RCTs. Twenty-five studies (RWD, n = 10; RCT, n = 15) reported hypoglycemia event rates in people with insulin-treated T2DM. For T2DM basal-oral therapy; the highest rates were observed in RWD studies, although there was an overlap with RCT rates. For basal-bolus therapy, there was considerable between-study variability but higher rates of severe and non-severe hypoglycemia were generally observed in RWD studies. For T2DM premix insulin, reported rates of hypoglycemia in RWD studies and RCTs were similar. CONCLUSION: We found that higher rates of hypoglycemia are observed in real-world settings compared with clinical trial settings, although there is a large degree of overlap. Due to the inherent constraints of RCTs, they are likely to underestimate the burden of hypoglycemia in clinical practice. Further, high quality RWD are needed to determine a more accurate incidence of hypoglycemia in clinical practice. PMID- 26886443 TI - Epidemiological Aspects of Dermatophytosis in Khuzestan, southwestern Iran, an Update. AB - Dermatophytosis is among the most common superficial mycoses in Iran. The purpose of this report was to update the clinical and mycological features of human dermatophytosis in the Khuzestan, southwestern Iran. In the framework of a one year survey, a total of 4120 skin, hair and nail samples obtained from the outpatients with symptoms suggestive of tinea were analyzed by using direct microscopy, culture and molecular identification methods. Strains isolated from cultures were subjected to amplification of the nuclear rDNA ITS regions in a PCR assay followed by an early established RFLP analysis. For confirmation of species identification, 100 isolates as representatives of all presumable species were subjected to ITS sequencing. Infection was confirmed in 1123 individuals (27.25 %) in the age range of 1-89 years by direct microscopy and/or culture including 603 males versus 520 females. Frequencies of infections were the highest and the lowest in age groups of 21-30 and 11-20 years, respectively. Tinea corporis was the most prevalent clinical manifestation followed by tinea cruris, tinea capitis, tinea manuum, tinea pedis, tinea unguium, tinea faciei and tinea barbae. Trichophyton interdigitale (58.7 %) was the most dominant isolate followed by Epidermophyton floccosum (35.4 %), Microsporum canis (3 %), T. rubrum (1.5 %), T. species of Arthroderma benhamiae (0.5 %), T. tonsurans (0.3 %) and T. violaceum (0.3 %). Other species included M. gypseum, M. fulvum and T. verrucosum (each one 0.1 %). Such a high occurrence of infection with T. interdigitale, which has not been reported from Iran, is due to the use of accurate molecular methods based on new species concept in dermatophytes. The prevalence of dermatophytoses caused by zoophilic species remarkably increased and Trichophyton species of A. benhamiae has emerged as a new agent of dermatophytosis in southwestern Iran, while infections due to anthropophilic species, except E. floccosum, took a decreasing trend. PMID- 26886444 TI - The Correlation Between Candida Colonization of Distinct Body Sites and Invasive Candidiasis in Emergency Intensive Care Units: Statistical and Molecular Biological Analysis. AB - Both statistical and molecular biological methods were used to evaluate the association between Candida colonization of different body sites and invasive candidiasis (IC) and analyse the potential infection sources of IC. Candida surveillance cultures from the urine, sputum, rectum and skin were performed on patients admitted to an emergency intensive care units (EICU) of a tertiary care hospital in Shanghai, China, from February 2014 to January 2015. Specimens were collected once a week at admission and thereafter. The patients' clinical data were collected, and Candida isolates were genotyped using polymorphic microsatellite markers. A total of 111 patients were enrolled. Patients with positive urine (23.3 vs. 2.5 %, p = 0.001) and rectal swab (13.6 vs. 0 %, p = 0.010) cultures were more likely to develop IC. However, the risk for IC was not significantly different among patients with and without respiratory (10.0 vs. 5.8 %, p = 0.503) and skin (33.3 vs. 6.5 %, p = 0.056) colonization. Gene microevolution frequently occurred at rectal swab and urine sites, and IC with possible source of infection was caused by rectal isolates (2/7), urine isolates (4/7) and sputum isolate (1/7).The colonization of gut and urinary tract maybe more relevant indicators of IC, which should be taken into consideration when selecting practical body sites for Candida surveillance cultures. PMID- 26886445 TI - Autophagy response in the liver of pigeon exposed to avermectin. AB - Pesticide residues are an important aspect of environmental pollution. Environmental avermectin residues have produced adverse effects in organisms. Many pesticides exert their toxic effects via the mechanism of autophagy. The purpose of this study was to examine the changes in autophagy levels and in autophagy-related genes, including LC3, Beclin 1, Dynein, ATG5, TORC1, and TORC2, resulting from exposure to subchronic levels of AVM in liver tissue in the king pigeon model. We observed abundant autophagic vacuoles with extensively degraded organelles, autophagosomal vacuoles, secondary lysosomes, and double-membrane structures in the liver. The expression levels of the autophagy-related genes LC3 I, LC3-II, Beclin 1, ATG5, and Dynein were up-regulated; however, TORC1 and TORC2 expression levels were down-regulated. These changes occurred in a concentration dependent manner after AVM exposure for 30, 60, and 90 days in pigeons. Taken together, these results suggested that AVM increased the autophagic flux and that upregulation of autophagy might be closely related to the hepatotoxicity of AVM in birds. PMID- 26886418 TI - Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. AB - BACKGROUND: Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. METHODS: In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. RESULTS: By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P<0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P<0.001), edema (35.6% vs. 24.9%, P<0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003). CONCLUSIONS: In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.). PMID- 26886447 TI - Effects of Transport and Storage Conditions on Gene Expression in Blood Samples. AB - BACKGROUND: Inappropriate handling of blood samples might induce or repress gene expression and/or lead to RNA degradation affecting downstream analysis. In particular, sample transport is a critical step for biobanking or multicenter studies because of uncontrolled variables (i.e., unstable temperature). We report the results of a pilot study implemented within the EC funded SPIDIA project, aimed to investigate the role of transport and storage of blood samples containing and not containing an RNA stabilizer. METHODS: Blood was collected from a single donor both in EDTA and in PAXgene Blood RNA tubes. Half of the samples were sent to a second laboratory both at room temperature and at 4 degrees C, whereas the remaining samples were stored at room temperature and at 4 degrees C. Gene expression of selected genes (c-FOS, IL-1beta, IL-8, and GAPDH) known to be induced or repressed by ex vivo blood handling and of blood-mRNA quality biomarkers identified and validated within the SPIDIA project, which allow for monitoring changes in unstabilized blood samples after collection and during transport and storage, were analyzed by RT-qPCR. RESULTS: If the shipment of blood in tubes not containing RNA stabilizer is not performed under a stable condition, gene profile studies can be affected by the effects of transport. Moreover, also controlled temperature shipment (4 degrees C) can influence the expression of specific genes if blood is collected in tubes not containing a stabilizer. CONCLUSION: The use of dedicated biomarkers or time course experiments should be performed in order to verify potential bias on gene expression analysis due to sample shipment and storage conditions. Alternatively, the use of RNA stabilizer containing tubes can represent a reliable option to avoid ex vivo RNA changes. PMID- 26886446 TI - Association of Genotyping of Bacillus cereus with Clinical Features of Post Traumatic Endophthalmitis. AB - Bacillus cereus is the second most frequent cause of post-traumatic bacterial endophthalmitis. Although genotyping of B. cereus associated with gastrointestinal infections has been reported, little is known about the B. cereus clinical isolates associated with post-traumatic endophthalmitis. This is largely due to the limited number of clinical strains available isolated from infected tissues of patients with post-traumatic endophthalmitis. In this study, we report successful isolation of twenty-four B. cereus strains from individual patients with different disease severity of post-traumatic endophthalmitis. Phylogenetic analysis showed that all strains could be categorized into three genotypes (GTI, GTII and GTIII) and the clinical score showed significant differences among these groups. We then further performed genotyping using the vrrA gene, and evaluated possible correlation of genotype with the clinical features of B. cereus-caused post-traumatic endophthalmitis, and with the prognosis of infection by conducting follow-up with patients for up to 2 months. We found that the disease of onset and final vision acuity were significantly different among the three groups. These results suggested that the vrrA gene may play a significant role in the pathogenesis of endophthalmitis, and genotyping of B. cereus has the potential for predicting clinical manifestation and prognosis of endophthalmitis. To the best of our knowledge, this is the first report of isolation of large numbers of clinical isolates of B. cereus from patients with endophthalmitis. This work sets the foundation for future investigation of the pathogenesis endophthalmitis caused by B. cereus infection. PMID- 26886448 TI - Impact of a Probiotic-Based Cleaning Intervention on the Microbiota Ecosystem of the Hospital Surfaces: Focus on the Resistome Remodulation. AB - BACKGROUND: Contamination of hospital surfaces by clinically-relevant pathogens represents a major concern in healthcare facilities, due to its impact on transmission of healthcare-associated infections (HAIs) and to the growing drug resistance of HAI-associated pathogens. Routinely used chemical disinfectants show limitations in controlling pathogen contamination, due to their inefficacy in preventing recontamination and selection of resistant strains. Recently we observed that an innovative approach, based on a cleanser added with spores of non-pathogenic probiotic Bacilli, was effective in stably counteracting the growth of several pathogens contaminating hospital surfaces. METHODS: Here, we wanted to study the impact of the Bacillus-based cleanser on the drug-resistance features of the healthcare pathogens population. In parallel, the ability of cleanser-derived Bacilli to infect hospitalized patients was also investigated. RESULTS: Collected data showed that Bacilli spores can germinate on dry inanimate surfaces, generating the bacterial vegetative forms which counteract the growth of pathogens and effectively substitute for them on treated surfaces. Strikingly, this procedure did not select resistant species, but conversely induced an evident decrease of antibiotic resistance genes in the contaminating microbial population. Also importantly, all the six HAI-positive patients hosted in the treated areas resulted negative for probiotic Bacilli, thus adding evidences to their safety-to-use. CONCLUSIONS: These results indicate that this probiotic based procedure is active not only in controlling surface microbial contamination but also in lowering drug-resistant species, suggesting that it may have relevant clinical and therapeutical implications for the management of HAIs. PMID- 26886449 TI - The combination effects of bendamustine with antimetabolites against childhood acute lymphoblastic leukemia cells. AB - Bendamustine combined with other drugs is clinically efficacious for some adult lymphoid malignancies, but to date there are no reports of the use of such combinatorial approaches in pediatric patients. We investigated the in vitro activity of bendamustine combined with other antimetabolite drugs on B cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines established from pediatric patients with refractory or relapsed ALL. We also developed a mathematically drown improved isobologram method to assess the data objectively. Three BCP-ALL cell lines; YCUB-2, YCUB-5, and YCUB-6, were simultaneously exposed to various concentrations of bendamustine and cladribine, cytarabine, fludarabine, or clofarabine. Cell growth inhibition was determined using the WST 8 assay. Combinatorial effects were estimated using our improved isobologram method with IC80 (drug concentration corresponding to 80 % of maximum inhibition). Bendamustine alone inhibited ALL cell growth with mean IC80 values of 11.30-18.90 MUg/ml. Combinations of bendamustine with other drugs produced the following effects: (1) cladribine; synergistic-to-additive on all cell lines; (2) cytarabine; synergistic-to-additive on YCUB-5 and YCUB-6, and synergistic-to antagonistic on YCUB-2; (3) fludarabine; additive-to-antagonistic on YCUB-5, and synergistic-to-antagonistic on YCUB-2 and YCUB-6; (4) clofarabine; additive-to antagonistic on all cell lines. Flow cytometric analysis also showed the combination effects of bendamustine and cladribine. Bendamustine/cladribine or bendamustine/cytarabine may thus represent a promising combination for salvage treatment in childhood ALL. PMID- 26886450 TI - In vitro alteration of hematological parameters and blood viscosity by the perfluorocarbon: Oxycyte. AB - While perfluorocarbons (PFCs) may be useful in some clinical situations, previous studies have shown that interferences with chemistry analytes can occur with blood samples containing PFCs. This in vitro study focused on how the PFC Oxycyte may affect hematology measurements in blood samples. Swine blood diluted with Oxycyte or saline (Controls) were analyzed for Hemoglobin (Hb), Mean Corpuscular Volume (MCV),Hematocrit (Hct) and Fluorocrit (Fct) using a HemaVet, ABL-735 (ABL), or microhematocrit. Ancillary tests (blood viscosity, electrolytes, cell counts, and red blood cell morphology) were performed secondarily. Increasing Oxycyte resulted in increases in MCV, Hct, and visible cell shape change and morphology vs. CONTROLS: Effects correlated with lower sodium in Oxycyte samples vs. CONTROLS: With increasing Oxycyte, Hb became higher than Controls or became unpredictable depending on the instrument (HemaVet or ABL, respectively). Fct was smaller than predicted and likely represented the heaviest components of Oxycyte. At >=50 % Oxycyte, RBC hemolysis rendered further measurements impractical. Viscosity first increased then decreased with increasing Oxycyte, peaking at ~40 % Oxycyte. Hct, MCV, Hb, and RBC morphology may be affected by Oxycyte. These observations correlated with lower sodium and increasing Oxycyte, causing hemolysis at high Oxycyte concentrations. These changes were due to alterations in the blood samples in vitro and this should be considered when interpreting hematology parameters from in vivo studies. PMID- 26886452 TI - Setting up an outpatient parenteral antimicrobial therapy (OPAT) unit in Switzerland: review of the first 18 months of activity. AB - Outpatient parenteral antimicrobial therapy (OPAT) has been recognised as a useful, cost-effective and safe alternative to inpatient treatment, but no formal OPAT unit existed in Switzerland until recently. In December 2013 an OPAT unit was established at Lausanne University Hospital. We review here the experience of this new OPAT unit after 18 months of activity. Patient characteristics, clinical activities and outcomes were recorded prospectively. Need and acceptance was evaluated as number of OPAT courses administered and number of patients refusing OPAT. Safety and efficacy were evaluated as: (1) adverse events linked to antimicrobials and catheters, (2) re-admission to hospital, (3) rate of treatment failures and (4) mortality. Over 18 months, 179 courses of OPAT were administered. Acceptance was high with only four patients refusing OPAT. Urinary tract infections with resistant bacteria and musculoskeletal infections were the most common diagnoses. Self-administration of antibiotics using elastomeric pumps became rapidly the most frequently used approach. Sixteen patients presented with adverse events linked to antimicrobials and catheters. OPAT-related readmissions occurred in nine patients. The overall cure rate was 94 %. This study shows that OPAT is very well accepted by patients and medical staff, even in a setting which has not used this type of treatment approach until now. Self-administration using elastomeric pumps proved to be particularly useful, safe and efficient. OPAT offers a good alternative to hospitalisation for patients presenting with infections due to resistant bacteria that cannot be treated orally anymore and for difficult to treat infections. PMID- 26886451 TI - Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm. AB - OBJECTIVE: Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55-80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI. STUDY DESIGN: This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children-Fourth Edition, Beery Visual-motor Integration test-Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis. RESULTS: DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years. CONCLUSION: The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm. PMID- 26886453 TI - Structure, toxicity and antibiotic activity of gramicidin S and derivatives. AB - Development of new antibiotics is declining whereas antibiotic resistance is rising, heralding a post-antibiotic era. Antimicrobial peptides such as gramicidin S (GS), exclusively topically used due to its hemolytic side-effect, could still be interesting as therapeutic compounds. By modifying the amino-acid composition of GS, we synthesized GS analogues. We now show that derivative VK7 has a lower MIC (7.8-31.2 MUg/ml, median 15.6 MUg/ml) against strains of multi drug resistant (MDR) Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa than GS has (3.9-62.5 MUg/ml, median 31.3 MUg/ml). Low MICs for both VK7 and GS were observed for Staphylococcus aureus and Enterococcus faecium. VK7 showed reduced haemolysis and less lactate dehydrogenase release. All compounds were fully bactericidal at MIC values. Modification of GS enables production of novel derivatives potentially useful for systemic treatment of human infections. PMID- 26886454 TI - When is mesh fixation in TAPP-repair of primary inguinal hernia repair necessary? The register-based analysis of 11,230 cases. AB - Whereas for TEP the guidelines do not recommend mesh fixation on the basis of meta-analyses regardless of the defect size, for TAPP mesh fixation can be omitted only up to a defect size of 3 cm because of the paucity of studies on this topic. Hence, this study now seeks to explore this subject on the basis of prospective data from the Herniamed Hernia Registry. In the period September 01, 2009, to January 31, 2014, 11,228 male patients were operated on with the TAPP technique for a primary unilateral inguinal hernia and were followed up for 1 year. Mesh fixation was used for 7422 (66.1 %) of these patients and no mesh fixation for 3806 patients (33.9 %). Unadjusted analysis did not find any significant difference in the recurrence rate (0.88 % with fixation vs. 1.1 % without fixation; p = 0.259). Multivariable analysis of all potential influence factors (age, ASA, BMI, risk factors, defect size, mesh fixation, localization of defect, mesh size) did not identify any factor that impacted recurrence on 1-year follow-up. Only for medial and combined defect localization versus lateral localization was a highly significant effect identified (p < 0.001). With mesh fixation and larger mesh size, it was possible to significantly reduce the recurrence rate for larger medial hernias in this series (p = 0.046). For TAPP repair of an inguinal hernia, mesh fixation is not necessary in a significant number of patients. Patients with a medial and combined hernia are at higher risk of recurrence. In the patient series analyzed, it was possible to significantly reduce the recurrence rate with mesh fixation and larger mesh size for medial defects. PMID- 26886455 TI - siRNA Targeting the 2Apro Genomic Region Prevents Enterovirus 71 Replication In Vitro. AB - Enterovirus 71 (EV71) is the most important etiological agent of hand, foot, and mouth disease (HFMD) in young children, which is associated with severe neurological complications and has caused significant mortalities in recent HFMD outbreaks in Asia. However, there is no effective antiviral therapy against EV71. In this study, RNA interference (RNAi) was used as an antiviral strategy to inhibit EV71 replication. Three small interfering RNAs (siRNAs) targeting the 2Apro region of the EV71 genome were designed and synthesized. All the siRNAs were transfected individually into rhabdomyosarcoma (RD) cells, which were then infected with strain EV71-2006-52-9. The cytopathic effects (CPEs) in the infected RD cells, cell viability, viral titer, and viral RNA and protein expression were examined to evaluate the specific viral inhibition by the siRNAs. The results of cytopathogenicity and MTT tests indicated that the RD cells transfected with the three siRNAs showed slight CPEs and significantly high viability. The 50% tissue culture infective dose (TCID50) values demonstrated that the viral titer of the groups treated with three siRNAs were lower than those of the control groups. qRT-PCR and western blotting revealed that the levels of viral RNA and protein in the RD cells treated with the three siRNAs were lower than those in the controls. When RD cells transfected with siRNAs were also infected with strain EV71-2008-43-16, the expression of the VP1 protein was significantly inhibited. The levels of interferon alpha (IFN-alpha) and IFN-beta did not differ significantly in any group. These results suggest that siRNAs targeting the 2Apro region of the EV71 genome exerted antiviral effects in vitro. PMID- 26886456 TI - Averting the legacy of kidney disease: focus on childhood. PMID- 26886457 TI - Femoral Neck Stress Fractures in Children Younger Than 10 Years of Age. AB - BACKGROUND: Femoral neck stress fractures are rare in healthy children, with only 9 cases previously reported. The present article reviews our institutional experience with femoral neck stress fractures in children younger than 10 years of age, to highlight the unique features of this condition. METHODS: We undertook a retrospective review of clinical records of patients who had been treated at our institution for an idiopathic femoral neck stress fracture between 2000 and 2014. To focus on children rather than adolescents, the World Health Organization's definition of adolescent as a person between 10 and 19 years of age was used; we thereby limited our analysis to patients younger than 10 years of age. RESULTS: The study included 6 patients (3 males, 3 females) treated for an idiopathic femoral neck stress fracture, with a mean age at diagnosis of 7.7 years (range, 5.2 to 8.9 y). All patients presented with a limp, which worsened with activity and had persisted for a mean of 5 weeks (range, 2 to 9 wk). None of the patients had experienced an increase in activity level or sporting volume before symptom onset. On examination, 3 patients experienced pain with terminal hip flexion and 3 patients demonstrated pain-free hip range of motion. Plain radiography demonstrated inferior femoral neck cortical disruption, suggesting a compression-type stress fracture mechanism. The diagnosis was confirmed by cross sectional imaging in all cases. All patients were initially treated with 6 to 8 weeks of non-weight-bearing followed by 4 to 6 weeks of partial weight-bearing, leading to complete healing in 4 patients. Two patients demonstrated incomplete healing and were managed with spica casting for an additional 6 weeks. CONCLUSIONS: Our case series illustrates the unique features of this rare condition in children, with a history and examination profile distinct from those of adolescents and adults. Compliance with weight-bearing restrictions is difficult in this population and hip spica casting may be required to permit complete healing. LEVEL OF EVIDENCE: Level IV-case series. PMID- 26886458 TI - External Rotation Predicts Outcomes After Closed Glenohumeral Joint Reduction With Botulinum Toxin Type A in Brachial Plexus Birth Palsy. AB - BACKGROUND: Few studies have investigated outcomes after adjunct botulinum toxin type A (BTX-A) injections into the shoulder internal rotator muscles during shoulder closed reduction and spica cast immobilization in children with brachial plexus birth palsy. The purpose of this study was to report success rates after treatment and identify pretreatment predictors of success. METHODS: Children with brachial plexus birth palsy who underwent closed glenohumeral joint reduction with BTX-A and casting were included. Minimum follow-up was 1 year. Included patients did not receive concomitant shoulder surgery nor undergo microsurgery within 8 months. Records were reviewed for severity of palsy, age, physical examination scores, passive external rotation (PER), and subsequent orthopaedic procedures (repeat injections, repeat reduction, shoulder tendon transfers, and humeral osteotomy). Treatment success was defined in 3 separate ways: no subsequent surgical reduction, no subsequent closed or surgical reduction, and no subsequent procedure plus adequate external rotation. RESULTS: Forty-nine patients were included. Average age at time of treatment was 11.5 months. Average follow-up was 21.1 months (range, 1 to 9 y). Thirty-two patients (65%) required repeat reduction (closed or surgical). Only 16% of all patients obtained adequate active external rotation without any subsequent procedure. Increased PER (average 41+/-14 degrees, odds ratio=1.21, P=0.01) and Active Movement Scale external rotation (average 1.3, odds ratio=2.36, P=0.02) predicted optimal treatment success. Limited pretreatment PER (average -1+/-17 degrees) was associated with treatment failure. Using the optimal definition for success, all patients with pretreatment PER>30 degrees qualified as successes and all patients with PER<15 degrees were treatment failures. CONCLUSIONS: Pretreatment PER>30 degrees can help identify which patients are most likely to experience successful outcomes after shoulder closed reduction with BTX-A and cast immobilization. However, a large proportion of these patients will still have mild shoulder subluxation or external rotation deficits warranting subsequent intervention. LEVEL OF EVIDENCE: Level IV-therapeutic. PMID- 26886459 TI - Dynamic Splinting in Children and Adolescents With Stiffness After Knee Surgery. AB - PURPOSE: The purpose of this study was to investigate the indications and outcomes of dynamic splinting (DS) of the arthrofibrotic knee in the pediatric population. METHODS: Seventy-four patients (41 males, 33 females) with postoperative arthrofibrosis treated with DS after an index knee surgery were reviewed. Median age was 13 years (range, 4 to 18 y), and median follow-up was 17 months (interquartile range, 10 to 28 mo). Demographics, index surgery procedure, preoperative and postoperative knee range of motion (ROM) measurements, treatment length and subsequent need for manipulation under anesthesia (MUA), and surgical lysis of adhesions (LOA) were evaluated. A ROM deficit was defined as lack of extension >=10 degrees or lack of flexion <130 degrees. Successful improvement of ROM was defined as an increase of >=10 degrees in flexion, extension, or both. There were 23 patients with flexion deficit only, 17 with extension deficit only, and 34 with combined flexion and extension deficits. Wilcoxon signed-rank test was used to assess median improvement in ROM. Patients were classified into 4 surgical groups: anterior cruciate ligament (ACL) reconstruction without meniscal repair (n=19), ACL reconstruction with meniscal repair (n=12), tibial spine fracture repair (n=21), and other (n=22). Multivariable logistic regression was used to identify independent predictors of failure of DS requiring MUA and LOA. RESULTS: A total of 57 patients with flexion deficits showed median improvement of 30 degrees in flexion (95% confidence interval, 0-90 degrees; P<0.001), and 51 patients with extension deficits showed median improvement of 7 degrees in extension (95% confidence interval, 0-60 degrees; P<0.001). DS was associated with ROM improvement in 84% and avoided the need for surgery in 58% of all 74 patients included in the study. Multivariate analysis of the ACL with meniscus repair subgroup revealed that each 1-month delay in DS treatment was associated with a 5-fold increased risk of undergoing a LOA (P=0.007). Thirty-six (63%) patients with flexion deficit avoided need for surgery, whereas 26 (51%) patients with extension deficits avoided surgery. CONCLUSIONS: Our data suggest that DS is an effective method to increase knee ROM and reduce the need for subsequent MUA/LOA in the pediatric and adolescent patient with arthrofibrosis after an index knee surgery. LEVEL OF EVIDENCE: Level IV-retrospective case series. PMID- 26886460 TI - Body Image and Quality of Life and Brace Wear Adherence in Females With Adolescent Idiopathic Scoliosis. AB - BACKGROUND: Clinical evidence regarding the ability of braces to decrease the risk of curve progression to surgical threshold in patients with adolescent idiopathic scoliosis (AIS) continues to strengthen. Unfortunately, there is still a great deal of uncertainty regarding the impact of brace wear on psychosocial well-being or the impact of psychological well-being on brace wear adherence. The purpose of this study is to evaluate psychosocial well-being, in particular body image and quality of life (QOL), and brace wear adherence in female AIS patients undergoing brace treatment. METHODS: The Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST) was a multicenter, controlled trial using randomized and preference assignments into an observation or brace treatment group. BrAIST patients were skeletally immature adolescents diagnosed with AIS having moderate curve sizes (20 to 40 degrees). Patients in the bracing group were instructed to wear a thoracolumbosacral orthosis, at least 18 h/d. Scores on the Spinal Appearance Questionnaire and the PedsQL4.0 Generic Scales from 167 female BrAIST patients who were randomized to brace treatment (n=58) and patients who chose brace treatment (n=109) were analyzed. RESULTS: At baseline and at 12 months, no differences were found between the least-adherent brace wear group (<6 h/d) and most-adherent brace wear group (>=12 h/d) patients in terms of major curve, body image, and QOL. In the most-adherent group, poorer body image scores were significantly correlated with poorer QOL scores at baseline, at 6 months, and at 12 months but not at 18 months. In general, body image scores and QOL scores were not significantly correlated in the least-adherent group. When comparing patients that had a >=6 degree increase of their major curve between baseline and 12 months to patients that did not, there were no significant differences in body image or QOL scores. CONCLUSIONS: For females adolescents with AIS, body image and QOL do not have a significant impact on brace wear adherence and are subsequently not significantly impacted by brace wear. LEVEL OF EVIDENCE: Level II-therapeutic (prospective comparative study). PMID- 26886461 TI - Quantifying Anesthesia Exposure in Growing Rod Treatment for Early Onset Scoliosis. AB - BACKGROUND: Growing rod (GR) treatment for early-onset scoliosis requires repeated anesthesia exposure (AE). At a minimum, GR treatment requires AE for diagnostic imaging, index GR surgery, periodic lengthenings, and final fusion. Adjunct procedures and complication-related procedures also increase AE. To our knowledge, this is the first study to quantify AE in GR treatment and to establish preoperative expectations. METHODS: A single-center retrospective review of 16 patients who completed GR treatment and underwent final fusion. Duration of all AE related to GR treatment for "standard" care procedures (ie, advanced imaging, index surgery, lengthenings, final fusion) and "associated" care procedures (ie, revisions, adjunctive surgical procedures, wound-related complications) were reviewed. Etiologies were classified per the classification of early-onset scoliosis. Mean total anesthesia time (TAT) was tallied and analyzed for standard care and associated care procedures. RESULTS: There were 5 syndromic, 8 neuromuscular, and 3 idiopathic patients. The mean age at the first AE event related to GR treatment was 7.4 years (range, 3.8 to 11 y). Mean age at the index GR surgery and final fusion was 8.1 years (range, 3.9 to 14.4 y) and 12.8 years (range, 9.7 to 19 y), respectively. The percentage of TAT for each procedural category was 7% for advanced imaging, 14% for index GR, 14% for lengthenings, 21% for final fusion, 27% for revisions, 9% for adjunct surgery, and 9% for wound complications. Standard care procedures accounted for 55% of TAT, whereas associated care procedures accounted for 45%. CONCLUSIONS: This study quantified expected duration of AE in GR treatment. Revisions and final fusion contributed most to TAT. Given the recent controversy of repeated AE in young children, efficiency measures should be implemented to reduce AE and avoid duplication without compromising the goals of surgical treatment. Associated care procedures accounted for 45% of the total AE. LEVEL OF EVIDENCE: Level IV. PMID- 26886464 TI - Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris. AB - Alongside the remarkable advances in medical and invasive therapies for the treatment of ischemic heart disease, an increasing number of patients with advanced coronary artery disease unsuitable for revascularization continue to suffer from angina pectoris despite optimal medical therapy. Patients with chronic angina have poor quality of life and increased levels of anxiety and depression. A considerable number of innovative therapeutic modalities for the treatment of chronic angina have been investigated over the years; however, none of these therapeutic options has become a standard of care, and none are widely utilized. Current treatment options for refractory angina focus on medical therapy and secondary risk factor modification. Interventions to create increased pressure in the coronary sinus may alleviate myocardial ischemia by forcing redistribution of coronary blood flow from the less ischemic subepicardium to the more ischemic subendocardium, thus relieving symptoms of ischemia. Percutaneous, transvenous implantation of a balloon expandable, hourglass-shaped, stainless steel mesh in the coronary sinus to create a fixed focal narrowing and to increase backwards pressure, may serve as a new device-based therapy destined for the treatment of refractory angina pectoris. PMID- 26886463 TI - Hair cell stereociliary bundle regeneration by espin gene transduction after aminoglycoside damage and hair cell induction by Notch inhibition. AB - Once inner ear hair cells (HCs) are damaged by drugs, noise or aging, their apical structures including the stereociliary arrays are frequently the first cellular feature to be lost. Although this can be followed by progressive loss of HC somata, a significant number of HC bodies often remain even after stereociliary loss. However, in the absence of stereocilia they are nonfunctional. HCs can sometimes be regenerated by Atoh1 transduction or Notch inhibition, but they also may lack stereociliary bundles. It is therefore important to develop methods for the regeneration of stereocilia, in order to achieve HC functional recovery. Espin is an actin-bundling protein known to participate in sterociliary elongation during development. We evaluated stereociliary array regeneration in damaged vestibular sensory epithelia in tissue culture, using viral vector transduction of two espin isoforms. Utricular HCs were damaged with aminoglycosides. The utricles were then treated with a gamma-secretase inhibitor, followed by espin or control transduction and histochemistry. Although gamma-secretase inhibition increased the number of HCs, few had stereociliary arrays. In contrast, 46 h after espin1 transduction, a significant increase in hair-bundle-like structures was observed. These were confirmed to be immature stereociliary arrays by scanning electron microscopy. Increased uptake of FM1-43 uptake provided evidence of stereociliary function. Espin4 transduction had no effect. The results demonstrate that espin1 gene therapy can restore stereocilia on damaged or regenerated HCs. PMID- 26886465 TI - Marijuana Use and Cardiovascular Disease. AB - Marijuana is currently the most used illicit substance in the world. With the current trend of decriminalization and legalization of marijuana in the US, physicians in the US will encounter more patients using marijuana recreationally over a diverse range of ages and health states. Therefore, it is relevant to review marijuana's effects on human cardiovascular physiology and disease. Compared with placebo, marijuana cigarettes cause increases in heart rate, supine systolic and diastolic blood pressures, and forearm blood flow via increased sympathetic nervous system activity. These actions increase myocardial oxygen demand to a degree that they can decrease the time to exercise-induced angina in patients with a history of stable angina. In addition, marijuana has been associated with triggering myocardial infarctions (MIs) in young male patients. Smoking marijuana has been shown to increase the risk of MI onset by a factor of 4.8 for the 60 minutes after marijuana consumption, and to increase the annual risk of MI in the daily cannabis user from 1.5% to 3% per year. Human and animal models suggest that this effect may be due to coronary arterial vasospasm. However, longitudinal studies have indicated that marijuana use may not have a significant effect on long-term mortality. While further research is required to definitively determine the impact of marijuana on cardiovascular disease, it is reasonable to recommend against recreational marijuana use, especially in individuals with a history of coronary artery disorders. PMID- 26886466 TI - PCSK9 Inhibitors: An Innovative Approach to Treating Hyperlipidemia. AB - Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are novel agents indicated for the treatment of hyperlipidemia. Inhibition of PCSK9 produces an increase in surface low-density lipoprotein (LDL) receptors and increases removal of LDL from the circulation. Alirocumab (Praluent; Sanofi/Regeneron, Bridgewater, NJ) and evolocumab (Repatha; Amgen, Thousand Oaks, CA) are currently available and approved for use in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, and clinical atherosclerotic cardiovascular disease. Bococizumab (RN316; Pfizer, New York, NY) is currently being studied in similar indications, with an estimated approval date in late 2016. The pharmacodynamic effects of PCSK9 inhibitors have been extensively studied in various patient populations. They have been shown to produce significant reductions in LDL and are well tolerated in clinical studies, but they are very costly when compared with statins, the current mainstay of hyperlipidemia treatment. Clinical outcome studies are underway, but not yet available; however, meta-analyses have pointed to a reduction in cardiovascular death and cardiovascular events with the use of PCSK9 inhibitors. This review will discuss the novel mechanism of action of PCSK9 inhibitors, the results of clinical studies, and the clinical considerations of these agents in current therapy. PMID- 26886467 TI - The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes. AB - Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice. PMID- 26886468 TI - Theory of Mind and Executive Control Deficits in Typically Developing Adults and Adolescents with High Levels of Autism Traits. AB - Autism spectrum disorder (ASD) is characterised by profound difficulties in empathic processing and executive control. Whilst the links between these processes have been frequently investigated in populations with autism, few studies have examined them at the subclinical level. In addition, the contribution of alexithymia, a trait characterised by impaired interoceptive awareness and empathy, and elevated in those with ASD, is currently unclear. The present two-part study employed a comprehensive battery of tasks to examine these processes. Findings support the notion that executive function and theory of mind are related abilities. They also suggest that individuals with elevated levels of autism-like traits experience a partially similar pattern of social and executive function difficulties to those diagnosed with ASD, and that these impairments are not explained by co-occurring alexithymia. PMID- 26886470 TI - Brief Report: Assessment of Intervention Effects on In Vivo Peer Interactions in Adolescents with Autism Spectrum Disorder (ASD). AB - This study aimed to evaluate the effectiveness of a randomized controlled trial of a social skills intervention, the Program for the Education and Enrichment of Relational Skills (PEERS: Laugeson et al. in J Autism Dev Disord 39(4): 596-606, 2009), by coding digitally recorded social interactions between adolescent participants with ASD and a typically developing adolescent confederate. Adolescent participants engaged in a 10-min peer interaction at pre- and post treatment. Interactions were coded using the Contextual Assessment of Social Skills (Ratto et al. in J Autism Dev Disord 41(9): 1277-1286, 2010). Participants who completed PEERS demonstrated significantly improved vocal expressiveness, as well as a trend toward improved overall quality of rapport, whereas participants in the waitlist group exhibited worse performance on these domains. The degree of this change was related to knowledge gained in PEERS. PMID- 26886471 TI - Pediatrician Sees Long Road Ahead for Flint After Lead Poisoning Crisis. PMID- 26886472 TI - Association between histological features and clinical features of patients with biopsy positive giant cell arteritis. AB - OBJECTIVES: The aim of this study was to investigate the association between histological biopsy features and clinical features, such as blindness, in patients with biopsy positive giant cell arteritis (GCA). METHODS: Positive temporal artery biopsies registered on the South Australian Giant Cell Arteritis Registry were identified between 1991 and 2013 (n=186). Clinical and serological data was recorded using both patient questionnaire and case note review. Patients without clinical data were excluded from the analysis (n=42). Statistical analysis was performed using chi-squared and Wilcoxon's tests. RESULTS: 144 biopsy positive GCA cases were analysed. The mean age at biopsy was 77 years; 71% were female. In total 25% experienced blindness. Although not individually significant, transmural inflammation (p=0.11), luminal thrombus (p=0.17) and giant cells (p=0.20) were more frequent in patients who suffered blindness, whereas fragmentation of the internal elastic lamina (p=0.04), and intimal thickening (p=0.02) were more frequent in patients without blindness. The presence of giant cells was associated with transmural inflammation (p=0.06), jaw claudication (p=0.02), and higher inflammatory markers. In contrast, characteristics of patients with intimal thickening included a lower frequency of giant cells (0.01) and jaw claudication (p=0.01), and lower inflammatory markers. CONCLUSIONS: Giant cells are strongly associated with jaw claudication and systemic markers of inflammation, perhaps reflecting more acute and aggressive disease. We did not find any histological features that were individually significantly associated with an increased risk of blindness in GCA patients. PMID- 26886469 TI - Attention Bias to Emotional Faces Varies by IQ and Anxiety in Williams Syndrome. AB - Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N = 46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ. PMID- 26886473 TI - Antibiotic use for irreversible pulpitis. AB - BACKGROUND: Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for emergency dental care. Apart from removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling into the tooth, removing the inflamed pulp (nerve) and cleaning the root canal. However, a significant number of dentists continue to prescribe antibiotics to stop the pain of irreversible pulpitis.This review updates the previous version published in 2013. OBJECTIVES: To assess the effects of systemic antibiotics for irreversible pulpitis. SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 27 January 2016); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 12); MEDLINE via Ovid (1946 to 27 January 2016); EMBASE via Ovid (1980 to 27 January 2016), ClinicalTrials.gov (to 27 January 2016) and the WHO International Clinical Trials Registry Platform (to 27 January 2016). There were no language restrictions in the searches of the electronic databases. SELECTION CRITERIA: Randomised controlled trials which compared pain relief with systemic antibiotics and analgesics, against placebo and analgesics in the acute preoperative phase of irreversible pulpitis. DATA COLLECTION AND ANALYSIS: Two review authors screened studies and extracted data independently. We assessed the quality of the evidence of included studies using GRADEpro software. Pooling of data was not possible and a descriptive summary is presented. MAIN RESULTS: One trial assessed at low risk of bias, involving 40 participants was included in this update of the review. The quality of the body of evidence was rated low for the different outcomes. There was a close parallel distribution of the pain ratings in both the intervention and placebo groups over the seven-day study period. There was insufficient evidence to claim or refute a benefit for penicillin for pain intensity. There was no significant difference in the mean total number of ibuprofen tablets over the study period: 9.2 (standard deviation (SD) 6.02) in the penicillin group versus 9.6 (SD 6.34) in the placebo group; mean difference -0.40 (95% confidence interval (CI) -4.23 to 3.43; P value = 0.84). This applied equally for the mean total number of Tylenol tablets: 6.9 (SD 6.87) used in the penicillin group versus 4.45 (SD 4.82) in the placebo group; mean difference 2.45 (95% CI -1.23 to 6.13; P value = 0.19). Our secondary outcome on reporting of adverse events was not addressed in this study. AUTHORS' CONCLUSIONS: This systematic review which was based on one low powered small sample trial assessed as at low risk of bias, illustrates that there is insufficient evidence to determine whether antibiotics reduce pain or not compared to not having antibiotics. The results of this review confirm the necessity for further larger sample and methodologically sound trials that can provide additional evidence as to whether antibiotics, prescribed in the preoperative phase, can affect treatment outcomes for irreversible pulpitis. PMID- 26886474 TI - Effects of Virtual Reality Training (Exergaming) Compared to Alternative Exercise Training and Passive Control on Standing Balance and Functional Mobility in Healthy Community-Dwelling Seniors: A Meta-Analytical Review. AB - BACKGROUND: Balance training is considered an important means to decrease fall rates in seniors. Whether virtual reality training (VRT) might serve as an appropriate treatment strategy to improve neuromuscular fall risk parameters in comparison to alternative balance training programs (AT) is as yet unclear. OBJECTIVE: To examine and classify the effects of VRT on fall-risk relevant balance performance and functional mobility compared to AT and an inactive control condition (CON) in healthy seniors. DATA SOURCES: The literature search was conducted in five databases (CINAHL, EMBASE, ISI Web of Knowledge, PubMed, SPORTDiscus). The following search terms were used with Boolean conjunction: (exergam* OR exer-gam* OR videogam* OR video-gam* OR video-based OR computer based OR Wii OR Nintendo OR X-box OR Kinect OR play-station OR playstation OR virtua* realit* OR dance dance revolution) AND (sport* OR train* OR exercis* OR intervent* OR balanc* OR strength OR coordina* OR motor control OR postur* OR power OR physical* OR activit* OR health* OR fall* risk OR prevent*) AND (old* OR elder* OR senior*). STUDY SELECTION: Randomized and non-randomized controlled trials applying VRT as interventions focusing on improving standing balance performance (single and double leg stance with closed and open eyes, functional reach test) and functional mobility (Berg balance scale, Timed-up and go test, Tinetti test) in healthy community-dwelling seniors of at least 60 years of age were screened for eligibility. DATA EXTRACTION: Eligibility and study quality (PEDro scale) were independently assessed by two researchers. Standardized mean differences (SMDs) served as main outcomes for the comparisons of VRT versus CON and VRT versus AT on balance performance and functional mobility indices. Statistical analyses were conducted using a random effects inverse-variance model. RESULTS: Eighteen trials (mean PEDro score: 6 +/- 2) with 619 healthy community dwellers were included. The mean age of participants was 76 +/- 5 years. Meaningful effects in favor of VRT compared to CON were found for balance performance [p < 0.001, SMD: 0.77 (95 % CI 0.45-1.09)] and functional mobility [p = 0.004, SMD: 0.56 (95 % CI 0.25-0.78)]. Small overall effects in favor of AT compared to VRT were found for standing balance performance [p = 0.31, SMD: -0.35 (95 % CI -1.03 to 0.32)] and functional mobility [p = 0.05, SMD: -0.44 (95 % CI: 0.87 to 0.00)]. Sensitivity analyses between "weaker" (n = 9, PEDro <=5) and "stronger" (n = 9, PEDro >=6) studies indicated that weaker studies showed larger effects in favor of VRT compared to CON regarding balance performance (p < 0.001). CONCLUSIONS: Although slightly less effective than AT, VRT-based balance training is an acceptable method for improving balance performance as well as functional mobility outcomes in healthy community dwellers. VRT might serve as an attractive complementary training approach for the elderly. However, more high quality research is needed in order to derive valid VRT recommendations compared to both AT and CON. PMID- 26886477 TI - SOX2 Expression in Cervical Intraepithelial Neoplasia Grade 3 (CIN3) and Superficially Invasive (Stage IA1) Squamous Carcinoma of the Cervix. AB - The transcription factor SOX2 plays an important role in tissue development and differentiation. In the neoplastic context, SOX2 has been shown to potentiate tumor invasion, and increased SOX2 immunoreactivity has been demonstrated in a variety of epithelial and nonepithelial malignancies often correlating with adverse prognosis. There are limited data on SOX2 expression in cervical squamous neoplasia and in particular, no studies have compared staining in cervical intraepithelial neoplasia (CIN)3 and in superficially invasive (Stage IA1) squamous cell carcinomas (SCC). We examined SOX2 expression in 12 cervical biopsies showing CIN3 only and 30 specimens with an initial diagnosis of Stage IA1 SCC; 7 of the latter samples did not demonstrate residual invasive foci in the study slides but all showed CIN3. There was variable staining in CIN3 without stromal invasion but CIN3 adjacent to SCC was more often SOX2 positive with 70% cases showing diffuse staining. CIN within endocervical crypts often showed more extensive SOX2 expression and in some cases staining was restricted to areas of crypt involvement. In contrast to CIN, most SCCs were SOX2 negative and there was often an abrupt loss of expression at the tumor-stromal interface. In summary, CIN3 usually showed increased SOX2 expression compared with normal epithelium, particularly in areas of endocervical crypt involvement and adjacent to superficially invasive SCC. However, most invasive tumor cells were unstained suggesting downregulation of SOX2 during the initial stages of the invasive process. Progression of cervical squamous neoplasia may involve cyclical alterations in SOX2 activity. PMID- 26886475 TI - The Benefits of Natural Environments for Physical Activity. AB - Urbanisation has a profound effect on both people and the environment, as levels of physical activity decline and many natural ecosystems become lost or degraded. Here we draw on emerging research to examine the role of green spaces in providing a venue for outdoor physical activity, and in enhancing the benefit of a given amount of physical activity for urban residents. We identify critical knowledge gaps, including (1) whether (and for whom) levels of physical activity increase as new green spaces are introduced or old spaces reinvigorated; (2) which characteristics of nature promote physical activity; (3) the extent to which barriers to outdoor physical activity are environmental or social; and (4) whether the benefits of physical activity and experiences of nature accrue separately or synergistically. A clear understanding of these issues will help guide effective investment in green space provision, ecological enhancement and green exercise promotion. PMID- 26886478 TI - Photoelectron Spectroscopy of cis-Nitrous Acid Anion (cis-HONO(-)). AB - We report photoelectron spectra of cis-HONO(-) formed from an association reaction of OH(-) and NO in a pulsed, plasma-entrainment ion source. The experimental data are assigned to the cis-HONO(-) isomer, which is predicted to be the global minimum on the anion potential energy surface. We do not find evidence for a significant contribution from trans-HONO(-). Electron photodetachment of cis-HONO(-) with 1613, 1064, 532, 355, and 301 nm photons accesses the ground X (1)A' (S0) and excited a (3)A" (T1) states of neutral HONO. The photoelectron spectrum resulting from detachment forming cis-HONO (S0) exhibits a long vibrational progression, dominated by overtones and combination bands involving the central O-N stretching and ONO bending vibrations. This indicates that there is a significant change in the central O-N bond length between cis-HONO(-) and cis-HONO (S0). The electron affinity (EA) of cis-HONO is determined to be 0.356(8) eV. We also report the dissociation energy (D0) of cis HONO(-), forming OH(-) + NO, as 0.594(9) eV, which is a factor of 4 decrease in the central O-N bond strength compared to neutral cis-HONO. The T1 state of cis HONO is shown to be ~2.3 eV higher in energy than cis-HONO (S0). Electron photodetachment to form cis-HONO (T1) accesses a transition state along the HO-NO bond dissociation coordinate. The resulting photoelectron spectrum exhibits broad peaks spaced by the terminal N?O stretching frequency. Electronic structure calculations and photoelectron spectrum simulations reported here show very good agreement with the experimental data. PMID- 26886479 TI - Maintenance Treatment by Erlotinib and Toxic Cardiomyopathy: A Case Report. AB - Erlotinib maintenance treatment improves progression-free survival compared with observation after first-line chemotherapy in unselected advanced non-small cell lung cancer (NSCLC). Very few cardiac adverse effects have been observed in phase III studies on tyrosine kinase inhibitors (TKI). We report the case of a 71-year old woman with metastatic NSCLC treated with cisplatin/pemetrexed and then erlotinib maintenance therapy. After 26 months of TKI therapy, she developed dilated cardiomyopathy. Despite symptomatic treatment, left ventricular ejection fraction decreased to 25%. Ischemic heart disease was excluded by coronary angiography and cardiac magnetic resonance imaging, and no other cause was found. Erlotinib was stopped, and cardiac resynchronization therapy by pacemaker was initiated. This case report highlights the possible cardiotoxic effects of long term erlotinib and suggests the need for close clinical and echocardiographic follow-up of patients receiving long-term TKI therapy. PMID- 26886476 TI - A Review of the Anthropometric Characteristics, Grading and Dispensation of Junior and Youth Rugby Union Players in Australia. AB - The grading of Australian junior and youth rugby union players has received substantial media attention in recent years. Media reports have focussed on size mismatches observed between players, especially players with Polynesian heritage, and the concerned parents who fear for the safety of their child owing to perceived mismatches. Although such concerns are well meaning, few media reports recognise the need for substantial evidence to determine the best grading system for junior and youth rugby union players. The current study reviewed relevant literature pertinent to the grading and dispensation of junior and youth rugby union players. Using primary and secondary search strategies, a total of 33 articles reporting the anthropometric characteristics of junior and youth rugby players were identified. Anthropometric data from the literature were compared with normative population data and currently used dispensation criteria. Junior and youth rugby players were found to be taller and heavier than normative population data. Current dispensation criteria, in terms of body mass, were found to vary and it is suggested that criteria be revised and standardised across rugby unions throughout Australia. Although it is acknowledged that other factors are important for grading players, anthropometric characteristics should be considered as potential dispensation criteria to supplement current age-based grading for junior and youth rugby union players. Measuring the body mass and stature of each junior player upon pre-season registration is suggested, which would provide data to establish valid dispensation criteria for the following season. PMID- 26886480 TI - A new mechanism of post-transfer editing by aminoacyl-tRNA synthetases: catalysis of hydrolytic reaction by bacterial-type prolyl-tRNA synthetase. AB - Aminoacyl tRNA synthetases are enzymes that specifically attach amino acids to cognate tRNAs for use in the ribosomal stage of translation. For many aminoacyl tRNA synthetases, the required level of amino acid specificity is achieved either by specific hydrolysis of misactivated aminoacyl-adenylate intermediate (pre transfer editing) or by hydrolysis of the mischarged aminoacyl-tRNA (post transfer editing). To investigate the mechanism of post-transfer editing of alanine by prolyl-tRNA synthetase from the pathogenic bacteria Enterococcus faecalis, we used molecular modeling, molecular dynamic simulations, quantum mechanical (QM) calculations, site-directed mutagenesis of the enzyme, and tRNA modification. The results support a new tRNA-assisted mechanism of hydrolysis of misacylated Ala-tRNAPro. The most important functional element of this catalytic mechanism is the 2'-OH group of the terminal adenosine 76 of Ala-tRNAPro, which forms an intramolecular hydrogen bond with the carbonyl group of the alanine residue, strongly facilitating hydrolysis. Hydrolysis was shown by QM methods to proceed via a general acid-base catalysis mechanism involving two functionally distinct water molecules. The transition state of the reaction was identified. Amino acid residues of the editing active site participate in the coordination of substrate and both attacking and assisting water molecules, performing the proton transfer to the 3'-O atom of A76. PMID- 26886482 TI - The Ethics of Cloud Computing. AB - Cloud computing is rapidly gaining traction in business. It offers businesses online services on demand (such as Gmail, iCloud and Salesforce) and allows them to cut costs on hardware and IT support. This is the first paper in business ethics dealing with this new technology. It analyzes the informational duties of hosting companies that own and operate cloud computing datacentres (e.g., Amazon). It considers the cloud services providers leasing 'space in the cloud' from hosting companies (e.g., Dropbox, Salesforce). And it examines the business and private 'clouders' using these services. The first part of the paper argues that hosting companies, services providers and clouders have mutual informational (epistemic) obligations to provide and seek information about relevant issues such as consumer privacy, reliability of services, data mining and data ownership. The concept of interlucency is developed as an epistemic virtue governing ethically effective communication. The second part considers potential forms of government restrictions on or proscriptions against the development and use of cloud computing technology. Referring to the concept of technology neutrality, it argues that interference with hosting companies and cloud services providers is hardly ever necessary or justified. It is argued, too, however, that businesses using cloud services (e.g., banks, law firms, hospitals etc. storing client data in the cloud) will have to follow rather more stringent regulations. PMID- 26886481 TI - Lessons learned from narrative feedback of students on a geriatric training program. AB - Geriatrics continues to draw insufficient numbers of medical students today. Currently, little is known regarding how education can motivate students to choose geriatrics. The authors' aim was to examine geriatrics from the students' perspective to identify elements that can be useful in education and improving attitudes toward, interest in, and knowledge about geriatrics. The authors analyzed narrative reflection essays of 36 students and clarified the themes from the essays during focus group sessions. Four overarching themes that influenced students' perspective on geriatrics were identified: professional identity, perception of geriatrics, geriatric-specific problems, and learning environment. Students have an inaccurate image of clinical practice and the medical professional identity, which has a negative impact on their attitude toward, interest in, and knowledge of geriatrics. Furthermore, this study yielded the important role of the hidden curriculum on professional identity, the novelty of geriatric-specific problems to students, and the importance of educational approach and good role models. PMID- 26886483 TI - Are experiences of family and of organized violence predictors of aggression and violent behavior? A study with unaccompanied refugee minors. AB - BACKGROUND: There is strong support for familial abuse as a risk factor for later delinquency and violent offending, whereas empirical evidence about the contribution of experienced organized violence to the cycle of violence is less clear. Nevertheless not all abused children do become violent offenders. This raises the question of which factors influence these children's risk of future aggressive behavior. Recent evidence suggests that the trait of appetitive aggression plays an important role in the prediction of aggressive behavior. OBJECTIVE: The focus of the study is to investigate whether exposures to 1) organized; and 2) family violence equally contribute to aggressive behavior and how this is related to a trait of appetitive aggression. Furthermore it is of interest to uncover how the severity of posttraumatic stress disorder (PTSD) symptoms modulates associations between violent experiences and aggression. METHOD: To answer these questions, we investigated unaccompanied refugee minors who had been exposed to varying levels of both violence types. Using structured interviews, experiences of organized and familial violence, self-committed aggressive acts, the trait of appetitive aggression, and PTSD symptoms were assessed in 49 volunteers. RESULTS: A sequential regression analysis revealed that the trait of appetitive aggression and experienced family violence were independent and significant predictors of self-committed aggressive acts, altogether accounting for 70% of the variance. Exposure to organized violence, however, was not significantly associated with aggressive acts or appetitive aggression. PTSD symptom severity was not correlated with measures of aggression but with the exposure to familial and organized violence. CONCLUSIONS: Results suggest that in addition to the impact of family violence, an elevated trait of appetitive aggression plays a crucial role in aggressive behavior and should be considered in psychotherapeutic treatment. PMID- 26886484 TI - Challenging future, challenging past: the relationship of social integration and psychological impairment in traumatized refugees. AB - BACKGROUND: Refugees have been shown to present high prevalence rates of trauma related mental disorders. Despite their psychological impairment, they are expected to meet high functional requirements in terms of social integration into, and financial independence from, the host society. METHODS: This cross sectional study examined the relationship of mental health problems, post migration living difficulties (PMLD), and social integration in a sample of 104 refugees seeking treatment for severe posttraumatic stress and comorbid symptoms in two outpatient clinics in Switzerland. RESULTS: Despite an average time of residence in Switzerland of over 10 years, participants showed poor integration and a high number of PMLD. Integration difficulties were closely associated with psychological symptoms, but not with socio-demographic parameters such as education or visa status. CONCLUSIONS: Psychological impairment in treatment seeking traumatized refugees is associated with poor integration. To foster social integration, it is crucial to better understand and address the specific needs of this highly vulnerable population. PMID- 26886486 TI - Complex PTSD and phased treatment in refugees: a debate piece. AB - BACKGROUND: Asylum seekers and refugees have been claimed to be at increased risk of developing complex posttraumatic stress disorder (complex PTSD). Consequently, it has been recommended that refugees be treated with present-centred or phased treatment rather than stand-alone trauma-focused treatment. This recommendation has contributed to a clinical practice of delaying or waiving trauma-focused treatment in refugees with PTSD. OBJECTIVE: The aim of this debate piece is to defend two theses: (1) that complex trauma leads to complex PTSD in a minority of refugees only and (2) that trauma-focused treatment should be offered to all refugees who seek treatment for PTSD. METHODS: The first thesis is defended by comparing data on the prevalence of complex PTSD in refugees to those in other trauma-exposed populations, using studies derived from a systematic review. The second thesis is defended using conclusions of systematic reviews and a meta analysis of the efficacy of psychotherapeutic treatment in refugees. RESULTS: Research shows that refugees are more likely to meet a regular PTSD diagnosis or no diagnosis than a complex PTSD diagnosis and that prevalence of complex PTSD in refugees is relatively low compared to that in survivors of childhood trauma. Effect sizes for trauma-focused treatment in refugees, especially narrative exposure therapy (NET) and culturally adapted cognitive-behaviour therapy (CA CBT), have consistently been found to be high. CONCLUSIONS: Complex PTSD in refugees should not be assumed to be present on the basis of complex traumatic experiences but should be carefully diagnosed using a validated interview. In line with treatment guidelines for PTSD, a course of trauma-focused treatment should be offered to all refugees seeking treatment for PTSD, including asylum seekers. PMID- 26886485 TI - Prevalence and gender differences in symptomatology of posttraumatic stress disorder and depression among Iraqi Yazidis displaced into Turkey. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) and depression are common among populations displaced due to large-scale political conflicts and war. OBJECTIVE: The aim of this study is to investigate the prevalence and gender-based differences in symptoms of PTSD and depression among Iraqi Yazidis displaced into Turkey. METHOD: The study was conducted on 238 individuals who were evaluated using the Structured Clinical Interview for DSM-IV (SCID-I) and the Stressful Life Events Screening Questionnaire. RESULTS: Of the participants, 42.9% met the DSM-IV diagnostic criteria for PTSD, 39.5% for major depression, and 26.4% for both disorders. More women than men suffered from PTSD and major depression. More women than men with PTSD or depression reported having experienced or witnessed the death of a spouse or child. Women with PTSD reported flashbacks, hypervigilance, and intense psychological distress due to reminders of trauma more frequently than men. Men with PTSD reported feelings of detachment or estrangement from others more frequently than women. More depressive women than men reported feelings of guilt or worthlessness. CONCLUSIONS: PTSD and major depression affected women more frequently than men. While women tended to respond to traumatic stress by undermodulation of emotions and low self-esteem, men tended to respond by overmodulation of emotions. Rather than being a derivative of sex differences, this complementary diversity in response types between genders seems to be shaped by social factors in consideration of survival under extreme threat. PMID- 26886487 TI - Growing from experience: an exploratory study of posttraumatic growth in adolescent refugees. AB - OBJECTIVE: The aim of this study was to explore perceived posttraumatic growth (PTG) and its associations with potentially traumatic events (PTEs), dispositional optimism, perceived social support, posttraumatic stress disorder (PTSD) symptoms, and satisfaction with life (SWL) among adolescent refugees and asylum seekers. METHOD: A cross-sectional design was employed including 111 refugees, aged 12-17, that were recruited from asylum seeker centres throughout the Netherlands. Measurements included the revised Posttraumatic Growth Inventory for Children, Children's Impact of Event Scale, Multidimensional Scale of Perceived Social Support, The Life Orientation Test, and the Satisfaction with Life Scale. RESULTS: Participants reported mean PTG scores (20.2) indicating an average response of some perceived change, while reporting high levels of PTSD symptoms (30.6). PTG and PTSD symptoms were not related with each other (r=0.07, p=0.50). PTG was positively associated with dispositional optimism (r=0.41, p<0.01) and social support (r=0.43, p<0.01). A hierarchical regression analysis demonstrated that dispositional optimism (beta=0.33; p<0.05) and social support (beta=0.27; p<0.05) positively predicted PTG, explaining 22% of the PTG variance above demographic variables and PTEs. PTG was also positively related with SWL (r=0.37, p<0.01). CONCLUSIONS: Perceived PTG and PTSD symptoms appear to be independent constructs, which co-occur in adolescent refugees and asylum seekers. The relationship between PTG and mental health remains inconclusive; PTG was positively related to SWL and not associated with PTSD symptoms. Longitudinal research is required to determine causality between PTG and mental health in this refugee population confronted with many traumatic experiences and challenging migration tasks. PMID- 26886488 TI - Effects of acculturative stress on PTSD, depressive, and anxiety symptoms among refugees resettled in Australia and Austria. AB - BACKGROUND: Research indicates that exposure to war-related traumatic events impacts on the mental health of refugees and leads to higher rates of posttraumatic stress disorder (PTSD), depression, and anxiety symptoms. Furthermore, stress associated with the migration process has also been shown to impact negatively on refugees' mental health, but the extent of these experiences is highly debatable as the relationships between traumatic events, migration, and mental health outcomes are complex and poorly understood. OBJECTIVE: This study aimed to examine the influence of trauma-related and post-migratory factors on symptoms of PTSD, depression, and anxiety in two samples of Bosnian refugees that have resettled in two different host nations-Austria and Australia. METHOD: Using multiple recruitment methods, 138 participants were recruited to complete self report measures assessing acculturative stress, PTSD, depressive, and anxiety symptoms. RESULTS: Hierarchical regressions indicated that after controlling for age, sex, and exposure to traumatic events, acculturative stress associated with post-migratory experiences predicted severity of PTSD and anxiety symptoms, while depressive symptoms were only predicted by exposure to traumatic events. This model, however, was only significant for Bosnian refugees resettled in Austria, as PTSD, depressive, and anxiety symptoms were only predicted by traumatic exposure in the Bosnian refugees resettled in Australia. CONCLUSION: These findings point toward the importance of assessing both psychological and social stressors when assessing mental health of refugees. Furthermore, these results draw attention to the influence of the host society on post-migratory adaptation and mental health of refugees. Further research is needed to replicate these findings among other refugee samples in other host nations. PMID- 26886490 TI - Global mental health: trauma and adversity among populations in transition. PMID- 26886489 TI - Psychological trauma and posttraumatic stress disorder: risk factors and associations with birth outcomes in the Drakenstein Child Health Study. AB - BACKGROUND: Prenatal and peripartum trauma may be associated with poor maternal fetal outcomes. However, relatively few data on these associations exist from low middle income countries, and populations in transition. OBJECTIVE: We investigated the prevalence and risk factors for maternal trauma and posttraumatic stress disorder (PTSD), and their association with adverse birth outcomes in the Drakenstein Child Health Study, a South African birth cohort study. METHODS: Pregnant women were recruited from two clinics in a peri-urban community outside Cape Town. Trauma exposure and PTSD were assessed using diagnostic interviews; validated self-report questionnaires measured other psychosocial characteristics. Gestational age at delivery was calculated and birth outcomes were assessed by trained staff. Multiple logistic regression explored risk factors for trauma and PTSD; associations with birth outcomes were investigated using linear regression. Potential confounders included study site, socioeconomic status (SES), and depression. RESULTS: A total of 544 mother-infant dyads were included. Lifetime trauma was reported in approximately two-thirds of mothers, with about a third exposed to past-year intimate partner violence (IPV). The prevalence of current/lifetime PTSD was 19%. In multiple logistic regression, recent life stressors were significantly associated with lifetime trauma, when controlling for SES, study site, and recent IPV. Childhood trauma and recent stressors were significantly associated with PTSD, controlling for SES and study site. While no association was observed between maternal PTSD and birth outcomes, maternal trauma was significantly associated with a 0.3 unit reduction (95% CI: 0.1; 0.5) in infant head-circumference-for-age z-scores (HCAZ scores) at birth in crude analysis, which remained significant when adjusted for study site and recent stressors in a multivariate regression model. CONCLUSIONS: In this exploratory study, maternal trauma and PTSD were found to be highly prevalent, and preliminary evidence suggested that trauma may adversely affect fetal growth, as measured by birth head circumference. However, these findings are limited by a number of methodological weaknesses, and further studies are required to extend findings and delineate causal links and mechanisms of association. PMID- 26886491 TI - Oxidation of Aryl Diphenylmethyl Sulfides Promoted by a Nonheme Iron(IV)-Oxo Complex: Evidence for an Electron Transfer-Oxygen Transfer Mechanism. AB - The oxidation of a series of aryl diphenylmethyl sulfides (4-X-C6H4SCH(C6H5)2, where X = OCH3 (1), X = CH3 (2), X = H (3), and X = CF3 (4)) promoted by the nonheme iron(IV)-oxo complex [(N4Py)Fe(IV)?O](2+) occurs by an electron transfer oxygen transfer (ET-OT) mechanism as supported by the observation of products (diphenylmethanol, benzophenone, and diaryl disulfides) deriving from alpha-C-S and alpha-C-H fragmentation of radical cations 1(+*)-4(+*), formed besides the S oxidation products (aryl diphenylmethyl sulfoxides). The fragmentation/S oxidation product ratios regularly increase through a decrease in the electron donating power of the aryl substituents, that is, by increasing the fragmentation rate constants of the radical cations as indicated by a laser flash photolysis (LFP) study of the photochemical oxidation of 1-4 carried out in the presence of N-methoxyphenanthridinium hexafluorophosphate (MeOP(+)PF6(-)). PMID- 26886492 TI - [Deliberate release of the laryngeal adductor reflex via microdroplet impulses: Development of a device]. AB - BACKGROUND: The laryngeal adductor reflex (LAR), a reflexive vocal fold closing mechanism, includes an early, probably di- or oligosynaptic ipsilateral LAR1- and a late ipsilateral and contralateral LAR2 polysynaptic component. In a clinical evaluation of dysphagia the LAR can be triggered by air pulses or tactile stimuli and typically assessed only qualitatively. METHODOLOGY: The development and construction of a device that can selectively shoot very small water droplets (microdroplet impulse testing MIT). RESULTS: The MIT device has a water reservoir with an infinitely adjustable pressure. The opening period of the piezo electrically operated valve determines the droplet size. With a high-speed camera system, the change in the airspeed of the drop can be determined, depending on the set water reservoir pressure. With the knowledge of the droplet size, the shooting speed and the estimation of the distance between the valve and laryngeal mucosa or airspeed can be determined the muzzle energy. By mounting the MIT device to a high speed glottography system, the time between the impact of the droplet on the laryngeal mucosa and the start of the laryngeal adduction, the LAR latency can be determined using an image by image evaluation. DISCUSSION: In dysphagia with penetration or aspiration it is presumed that the protective function of the larynx is no longer adequately ensured. The MIT-LAR device provides a valid and reliable method to assess LAR quantitatively. Furthermore, it holds the promise of being a simple to handle method that can be used clinically for routine diagnostics. PMID- 26886493 TI - Prevalence and complications of MRI scans of cochlear implant patients : English version. AB - BACKGROUND: Cochlear implants (CI) are the preferred method of treatment for patients with severe to profound bilateral sensorineural hearing loss and unilateral deafness. For many years, because of the magnetic field applied during magnetic resonance imaging (MRI) examinations, MRI examinations were contraindicated for CI patients or feasible only under specific circumstances. MRI examinations of CI recipients entail complications and therefore preventive measures have to be considered. The aim of this study was to evaluate the prevalence of MRI scans in CI recipients and the occurrence of complications and furthermore to investigate the preventive measures taken in radiological daily routine. MATERIALS AND METHODS: A retrospective questionnaire was sent to 482 patients that received CIs from 1999-2013. Details of the MRI examination and subjective and objective incidents during and after the MRI scan were evaluated. RESULTS: A total of 204 CI recipients answered the retrospective questionnaire (42.3 %). Twenty patients (9.8 %) with 23 implants underwent a total of 33 MRI scans with their cochlear implant in place. In 16 cases the scanned region was the head (49 %). Preventive measures in the form of head bandages were taken in 20 cases (61 %). The most common complication was pain in 23 cases (70 %) and the most serious complication was the dislocation of the internal magnet in 3 cases (9 %). CONCLUSIONS: The number of CI recipients undergoing MRI scans is high. Possible complications and preventive measures attract too little attention in radiological daily routine. PMID- 26886494 TI - [Bony lacrimal duct stenosis and hand abnormalities as signs of systemic disease]. PMID- 26886496 TI - [Human polyomaviruses]. AB - Polyomaviruses belong to a group of viruses that has recently attracted the attention of many research groups. During 35 years, JC and BK viruses, known pathogens in immunocompromised patients, seemed to be the only human polyomaviruses. But in 2007, two other polyomaviruses, WU and KI, were isolated whose pathogenicity is still a matter of discussion. A year later, another human polyomavirus, associated with Merkel cell carcinoma, was identified, and seven more were described by the end of 2014. Some of them were found to be related to various diseases, others seem to be a part of the normal skin and mucosal microbiome. The article summarizes basic information about all so far described human polyomaviruses. PMID- 26886495 TI - The "parts and wholes" of face recognition: A review of the literature. AB - It has been claimed that faces are recognized as a "whole" rather than by the recognition of individual parts. In a paper published in the Quarterly Journal of Experimental Psychology in 1993, Martha Farah and I attempted to operationalize the holistic claim using the part/whole task. In this task, participants studied a face and then their memory presented in isolation and in the whole face. Consistent with the holistic view, recognition of the part was superior when tested in the whole-face condition compared to when it was tested in isolation. The "whole face" or holistic advantage was not found for faces that were inverted, or scrambled, nor for non-face objects, suggesting that holistic encoding was specific to normal, intact faces. In this paper, we reflect on the part/whole paradigm and how it has contributed to our understanding of what it means to recognize a face as a "whole" stimulus. We describe the value of part/whole task for developing theories of holistic and non-holistic recognition of faces and objects. We discuss the research that has probed the neural substrates of holistic processing in healthy adults and people with prosopagnosia and autism. Finally, we examine how experience shapes holistic face recognition in children and recognition of own- and other-race faces in adults. The goal of this article is to summarize the research on the part/whole task and speculate on how it has informed our understanding of holistic face processing. PMID- 26886497 TI - [Determination of the naturally occurring Q80K mutation in the HCV NS3 protease gene]. AB - OBJECTIVES: The aim was to introduce a diagnostic method for detecting variants of hepatitis C virus (HCV) with protease NS3 resistance primarily to simeprevir (Q80K mutation in HCV genotype 1a) and its subsequent use in routine practice. MATERIAL AND METHODS: The detection of HCV resistance-associated variants in the NS3 protease gene by sequence analysis was introduced in the molecular biology laboratory of University Hospital Hradec Kralove in 2015. The primers were designed by sequence analysis software Custom Primers - OligoPerfectTM Designer. The method was optimized for HCV genotype 1a. The search for variants was performed using two programs. RESULTS: A total of 16 patients with genotype 1a chronic hepatitis C have been examined since 2015. In five of them, the Q80K variant was detected. CONCLUSION: The development of resistance to antiviral therapy for chronic hepatitis C gained importance after the introduction of direct-acting antivirals. Given the relatively high prevalence of the Q80K mutation in HCV genotype 1a, it is crucial to confirm its presence or absence before the therapy is initiated. The reported method enables clear and early detection of the Q80K mutation. PMID- 26886498 TI - [Furuncular myiasis - 2 case reports]. AB - Furuncular myiasis caused by the larvae of the human botfly, Dermatobia hominis, is a common disease in tropical areas of Latin America and may therefore occur in travelers returning from that region. Outside the endemic areas, the diagnosis is often delayed because the disease is mistaken for a bacterial skin infection. Reported are two cases of furuncular myiasis in patients returning from Central and South America. PMID- 26886499 TI - A Methodological Review of Exploratory Factor Analysis in Sexuality Research: Used Practices, Best Practices, and Data Analysis Resources. AB - Sexuality researchers frequently use exploratory factor analysis (EFA) to illuminate the distinguishable theoretical constructs assessed by a set of variables. EFA entails a substantive number of analytic decisions to be made with respect to sample size determination, and how factors are extracted, rotated, and retained. The available analytic options, however, are not all equally empirically rigorous. We discuss the commonly available options for conducting EFA and which options constitute best practices for EFA. We also present the results of a methodological review of the analytic options for EFA used by sexuality researchers in more than 200 EFAs, published in more than 160 articles and chapters from 1974 to 2014, in a sample of sexuality research journals. Our review reveals that best practices for EFA are actually those least frequently used by sexuality researchers. We introduce freely available analytic resources to help make it easier for sexuality researchers to adhere to best practices when conducting EFAs in their own research. PMID- 26886500 TI - Fitting identity in the reasoned action framework: A meta-analysis and model comparison. AB - Several competing models have been put forth regarding the role of identity in the reasoned action framework. The standard model proposes that identity is a background variable. Under a typical augmented model, identity is treated as an additional direct predictor of intention and behavior. Alternatively, it has been proposed that identity measures are inadvertent indicators of an underlying intention factor (e.g., a manifest-intention model). In order to test these competing hypotheses, we used data from 73 independent studies (total N = 23,917) to conduct a series of meta-analytic structural equation models. We also tested for moderation effects based on whether there was a match between identity constructs and the target behaviors examined (e.g., if the study examined a "smoker identity" and "smoking behavior," there would be a match; if the study examined a "health conscious identity" and "smoking behavior," there would not be a match). Average effects among primary reasoned action variables were all substantial, rs = .37-.69. Results gave evidence for the manifest-intention model over the other explanations, and a moderation effect by identity-behavior matching. PMID- 26886501 TI - Transversus Abdominis Release as an Alternative Component Separation Technique for Ventral Hernia Repair. PMID- 26886502 TI - Anti-fibrotic characteristics of Vgamma9+ gammadelta T cells in systemic sclerosis. AB - OBJECTIVES: gammadelta T cells of the Vgamma9Vdelta2 subtype secrete anti fibrotic cytokines upon isopentenyl pyrophosphate (IPP) stimulation. In this study, we sought to compare IPP and Zoledronate, an up-regulator of IPP, effects on proliferation and cytokine secretion of Vgamma9+ T cells from systemic sclerosis (SSc) patients and healthy controls (HCs). We also examined the effect of IPP-triggered peripheral blood mononuclear cells (PBMC) on fibroblast procolla gen secretion. METHODS: PBMC from SSc patients and HCs were stimulated by increasing concentrations of Zoledronate, with or without IPP, and Vgamma9+ T cell percentages were calculated using FACScan analysis. Subsequently, PBMC were cultured with IPP or toxic shock syndrome toxin-1 (TSST-1), and contents of the anti-fibrotic cytokines tumour necrosis factor (TNF)-alpha and interferon (IFN) gamma were measured by ELISA kits. Finally, supernatants of IPP-triggered Vgamma9+ T cells from SSc patients were added to fibroblast cultures, and relative intensities of procollagen alpha1 chains were determined by densinometry. RESULTS: Higher concentrations of Zoledronate were required for maximal proliferation of Vgamma9+ T cells in 9 SSc patients compared to 9 HCs, irrespective of exogenous IPP. When compared to stimulation by TSST-1, a non Vgamma9+ selective reagent, secretion of the anti-fibrotic cytokines TNF-alpha and IFN-gamma in response to IPP was relatively diminished in SSc but not in HCs. Reduction of procollagen secretion by fibroblasts cultured with supernatants of IPP-stimulated PBMC was observed only in some SSc patients. CONCLUSIONS: Activated Vgamma9+ T cells could act as anti-fibrotic mediators in SSc, although decreased responsiveness to IPP may play a role in the pathological fibrosis of this disease. PMID- 26886503 TI - Smoking Prevention for Students: Findings From a Three-Year Program of Integrated Harm Minimization School Drug Education. AB - BACKGROUND: This study investigated the impact of the Drug Education in Victorian Schools (DEVS) program on tobacco smoking. The program taught about licit and illicit drugs in an integrated manner over 2 years, with follow up in the third year. It focused on minimizing harm, rather than achieving abstinence, and employed participatory, critical-thinking and skill-based teaching methods. METHODS: A cluster-randomized, controlled trial of the program was conducted with a student cohort during years 8 (13 years), 9 (14 years), and 10 (15 years). Twenty-one schools were randomly allocated to the DEVS program (14 schools, n = 1163), or their usual drug education program (7 schools, n = 589). One intervention school withdrew in year two. RESULTS: There was a greater increase in the intervention students' knowledge about drugs, including tobacco, in all 3 years. Intervention students talked more with their parents about smoking at the end of the 3-year program. They recalled receiving more education on smoking in all 3 years. Their consumption of cigarettes had not increased to the same extent as controls at the end of the program. Their change in smoking harms, relative to controls, was positive in all 3 years. There was no difference between groups in the proportionate increase of smokers, or in attitudes towards smoking, at any time. CONCLUSIONS: These findings indicate that a school program that teaches about all drugs in an integrated fashion, and focuses on minimizing harm, does not increase initiation into smoking, while providing strategies for reducing consumption and harm to those who choose to smoke. PMID- 26886505 TI - Effects of multitasking on operator performance using computational and auditory tasks. AB - This study investigated the effects of multiple cognitive tasks on human performance. Twenty-four students at North Carolina A&T State University participated in the study. The primary task was auditory signal change perception and the secondary task was a computational task. Results showed that participants' performance in a single task was statistically significantly different from their performance in combined tasks: (a) algebra problems (algebra problem primary and auditory perception secondary); (b) auditory perception tasks (auditory perception primary and algebra problems secondary); and (c) mean false alarm score in auditory perception (auditory detection primary and algebra problems secondary). Using signal detection theory (SDT), participants' performance measured in terms of sensitivity was calculated as -0.54 for combined tasks (algebra problems the primary task) and -0.53 auditory perceptions the primary task. During auditory perception tasks alone, SDT was found to be 2.51. Performance was 83% in a single task compared to 17% when combined tasks. PMID- 26886504 TI - The Universal 3D3 Antibody of Human PODXL Is Pluripotent Cytotoxic, and Identifies a Residual Population After Extended Differentiation of Pluripotent Stem Cells. AB - Podocalyxin-like protein (PODXL) is a member of CD34 family proteins. It is the protein that carries many post-translational epitopes responsible for various pluripotent surface markers including TRA-1-60, TRA-1-81, GCTM2, GP200, and mAb84. However, PODXL has not attracted the attention of stem cell biologists. Here, we report several features of PODXL mRNA and protein in pluripotent stem cells. Similar to the modification-dependent pluripotent epitopes, PODXL transcripts and carrier protein are also features of pluripotency. PODXL is highly expressed in early human embryos from oocytes up to four-cell stages. During reprogramming of human cells to pluripotency, in contrast to TRA-1-60 and TRA-1-81, PODXL is activated by KLF4 at a very early time of reprogramming. Although TRA-1-60 and TRA-1-81 are completely lost upon differentiation, a residual PODXL(+) population exists even after extended differentiation and they were identified by the universal human PODXL epitope 3D3. Unlike TRA-1-60 and TRA 1-81 epitopes that are unique to primate pluripotent stem cells (PSCs), PODXL carrier protein can be used as a murine surface marker. Most importantly, antibody to 3D3 epitope causes massive necrosis and apoptosis of human PSCs (hPSCs). We suggest that 3D3 antibody could be employed to eliminate the tumorigenic pluripotent cells in hPSC-derived cells for cell transplantation. PMID- 26886506 TI - Photochemical Transformation of Aminoglycoside Antibiotics in Simulated Natural Waters. AB - Aminoglycoside antibiotics are widely used in human therapy and veterinary medicine. We report herein a detailed study on the natural-organic-matter- (NOM-) photosensitized degradation of aminoglycosides in aqueous media under simulated solar irradiation. It appears that the direct reaction of the excited states of NOM ((3)NOM*) with aminoglycosides is minor. The contributions of reactive oxygen species (ROSs) in the bulk solutions are also unimportant, as determined by an assessment based on steady-state concentrations and bimolecular reaction rate constants in a homogeneous reaction model. The inhibition of the photodegradation by isopropamide is rationalized through competitive sorption with aminoglycosides on the NOM surface, whereas the addition of isopropanol negligibly affects degradation because it quenches HO(*) in the bulk solution but not HO(*) localized on the NOM surface where aminoglycosides reside. Therefore, a sorption enhanced phototransformation mechanism is proposed. The sorption of aminoglycosides on NOM follows a dual-mode model involving Langmuir and linear isotherms. The steady-state concentration of HO(*) on the surface of NOM was calculated as 10(-14) M, 2 orders of magnitude higher than that in the bulk solution. This fundamental information is important in the assessment of the fate and transport of aminoglycosides in aqueous environments. PMID- 26886507 TI - Radiosynthesis and in Vivo Evaluation of Neuropeptide Y5 Receptor (NPY5R) PET Tracers. AB - Neuropeptide Y receptor type 5 (NPY5R) is a G-protein coupled receptor (GPCR) that belongs to the subfamily of neuropeptide receptors (NPYR) that mediate the action of endogenous neuropeptide Y (NPY). Animal models and preclinical studies indicate a role for NPY5R in the pathophysiology of depression, anxiety, and obesity and as a target of potential therapeutic drugs. To better understand the pathophysiological involvement of NPY5R, and to measure target occupancy by potential therapeutic drugs, it would be advantageous to measure NPY5R binding in vivo by positron emission tomography (PET). Four potent and selective NPY5R antagonists were radiolabeled via nucleophilic aromatic substitution reactions with [(18)F]fluoride. Of the four radioligands investigated, PET studies in anesthetized baboons showed that [(18)F]LuAE00654 ([(18)F]N-[trans-4-({[4-(2 fluoropyridin-3-yl)thiazol-2-yl]amino}methyl)cyclohexyl]propane-2-sulfonamide) penetrates blood brain barrier (BBB) and a small amount is retained in the brain. Slow metabolism of [(18)F]LuAE00654 was observed in baboon plasma. Blocking studies with a specific NPY5R antagonist demonstrated up to 60% displacement of radioactivity in striatum, the brain region with highest NPY5R binding. Our studies suggest that [(18)F]LuAE00654 can be a potential PET radiotracer for the quantification and occupancy studies of NPY5R drug candidates. PMID- 26886508 TI - Phonon dynamics of graphene on metals. AB - The study of surface phonon dispersion curves is motivated by the quest for a detailed understanding of the forces between the atoms at the surface and in the bulk. In the case of graphene, additional motivation comes from the fact that thermal conductivity is dominated by contributions from acoustic phonons, while optical phonon properties are essential to understand Raman spectra. In this article, we review recent progress made in the experimental determination of phonon dispersion curves of graphene grown on several single-crystal metal surfaces. The two main experimental techniques usually employed are high resolution electron energy loss spectroscopy (HREELS) and inelastic helium atom scattering (HAS). The different dispersion branches provide a detailed insight into the graphene-substrate interaction. Softening of optical modes and signatures of the substrate's Rayleigh wave are observed for strong graphene substrate interactions, while acoustic phonon modes resemble those of free standing graphene for weakly interacting systems. The latter allows determining the bending rigidity and the graphene-substrate coupling strength. A comparison between theory and experiment is discussed for several illustrative examples. Perspectives for future experiments are discussed. PMID- 26886509 TI - Evaluation of Sexual Function and Quality of Life in Women Treated for Stress Urinary Incontinence: Tension-Free Transobturator Suburethral Tape Versus Single Incision Sling. AB - OBJECTIVE: The aim of this study is to investigate the change in quality of life (QoL) and sexual function in women treated for pure stress urinary incontinence (SUI) using tension-free transobturator suburethral tape (TVT-O) and single incision sling (SIS) procedures. MATERIALS AND METHODS: From December 2013 to January 2015, a total of 48 female patients with pure SUI and normotonic urethra were consecutively enrolled and randomized into two treatment groups: TVT-O versus SIS. Both groups were homogeneous in the preoperative evaluation of age, body mass index, comorbidities, and pregnancies. Exclusion criteria included urge urinary incontinence, neurogenic bladder, previous surgery for incontinence, and mental or neurological disorders. The female sexual function and QoL were assessed preoperatively and postoperatively (3-12 months follow-up), using the Female Sexual Function Index (FSFI) and the International Consultation on Incontinence Questionnaire. RESULTS: A total of 42 patients completed both the questionnaires (21 patients in the TVT-O group and 21 patients in the SIS group, whereas 6 patients were lost to follow-up). Of the 19/21 (90.4%) of patients who successfully underwent the SIS procedure, 17 (80.9%) reported a complete resolution of SUI, whereas 2 (9.5%) reported an improvement in urinary incontinence at follow-up. In the TVT-O group, 18/21 (85.7%) of patients reported complete recovery, whereas 4.1% patients reported an improvement in the incontinence. The FSFI score increased significantly in both the SIS groups (from 23:51 +/- 3.78 to 27.42 +/- 3.34; p < 0.001) and TVT-O group (from 23.96 +/- 5:56 to 28.09 +/- 3.62) with no statistically significant differences between the two treatment groups. CONCLUSION: In our study, both slings showed a high rate of continence without any major complications. The sexual function also improved sharply in all the six FSFI domains, with no statistically significant difference between the two treatment groups. PMID- 26886510 TI - An Ex Vivo Phantom Validation Study of an MRI-Transrectal Ultrasound Fusion Device for Targeted Prostate Biopsy. AB - OBJECTIVES: To evaluate the ex vivo accuracy of an MRI-TRUS fusion device for guiding targeted prostate biopsies, to identify the origin of errors, and to evaluate the likelihood that lesions can be accurately targeted. MATERIALS AND METHODS: Three prostate phantoms were used to perform 27 biopsies using transperineal MRI-TRUS fusion. All phantoms underwent 3-T MRI. The prostate contour and nine lesions were delineated onto the MRI. A 3D-US dataset was generated and fused with the MRI. Per lesion, one needle was virtually planned. The postbiopsy needle location was virtually registered. The needle trajectory was marked using an MRI-safe guidewire. Postinterventional MRI was performed. The coordinates of the lesion on preinterventional MRI, the virtually planned needle, the virtually registered needle, and the marked needle trajectory on postinterventional MRI were documented and used to calculate the planning error (PE), targeting error (TE), and overall error (OE). Using the OE in the transversal plane, an upper one-sided tolerance interval was calculated to assess the likelihood that a biopsy needle was on target. RESULTS: In the transversal plane, the mean PE, TE, and OE were 1.18, 0.39, and 2.33 mm, respectively. Using a single biopsy core, the likelihood that lesions with a diameter of 2 mm can be accurately targeted is 26%; lesions of 3 mm 61%; lesions of 4 mm 86%; lesions of 5 mm 96%; and lesions of 6 mm 99%. The likelihood of accurate sampling increases if more biopsy cores are used. CONCLUSION: MRI-TRUS fusion allows for accurate sampling of MRI-identified lesions with an OE of 2.33 mm. Lesions with a diameter of 3 mm or more can be accurately targeted. These results should be considered the lower limit of in vivo accuracy. PMID- 26886511 TI - Mortality Rates during Cholera Epidemic, Haiti, 2010-2011. AB - The 2010 cholera epidemic in Haiti was one of the largest cholera epidemics ever recorded. To estimate the magnitude of the death toll during the first wave of the epidemic, we retrospectively conducted surveys at 4 sites in the northern part of Haiti. Overall, 70,903 participants were included; at all sites, the crude mortality rates (19.1-35.4 deaths/1,000 person-years) were higher than the expected baseline mortality rate for Haiti (9 deaths/1,000 person-years). This finding represents an excess of 3,406 deaths (2.9-fold increase) for the 4.4% of the Haiti population covered by these surveys, suggesting a substantially higher cholera mortality rate than previously reported. PMID- 26886512 TI - AMD3100: A Versatile Platform for CXCR4 Targeting (68)Ga-Based Radiopharmaceuticals. AB - CXCR4 is a G protein-coupled receptor (GPCR), which is overexpressed in numerous diseases, particularly in multiple cancers. Therefore, this receptor represents a valuable target for imaging and therapeutic purposes. Among the different approaches, which were developed for CXCR4 imaging, a CXCR4 antagonist biscyclam system (AMD3100, also called Mozobil), currently used in the clinic for the mobilization of hematopoietic stem cells, was radiolabeled with different radiometals such as (62)Zn, (64)Cu, (67)Ga, or (99m)Tc. However, cyclam is not an ideal chelator for most of these radiometals, and could lead to the release of the radionuclide in vivo. In the current study, a new family of CXCR4 imaging agents is presented, in which AMD3100 is used as a carrier for specific delivery of an imaging reporter, i.e., a (68)Ga complex for PET imaging. AMD3100 was functionalized on the phenyl moiety with different linkers, either ethylenediamine or diamino-polyethylene glycol 3 (PEG3). The resulting AMD3100 analogues were further coupled with two different chelators, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane 1-glutaric acid-4,7-acetic acid (NODAGA). Five potential CXCR4 targeting agents were obtained. The derived AMD3100-based ligands were labeled with (68)Ga, highlighting the influence of the spacer nature on the (68)Ga-labeling yield. The lipophilic character of the different systems was also investigated, as well as their affinity for the CXCR4 receptor. The most promising compound was further evaluated in vivo in H69 tumor xenografts by biodistribution and PET imaging studies, validating the proof of principle of our concept. PMID- 26886513 TI - Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice. AB - The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested. PMID- 26886515 TI - sigma-Hole Bond vs pi-Hole Bond: A Comparison Based on Halogen Bond. AB - The sigma-hole and pi-hole are the regions with positive surface electrostatic potential on the molecule entity; the former specifically refers to the positive region of a molecular entity along extension of the Y-Ge/P/Se/X covalent sigma bond (Y = electron-rich group; Ge/P/Se/X = Groups IV-VII), while the latter refers to the positive region in the direction perpendicular to the sigma framework of the molecular entity. The directional noncovalent interactions between the sigma-hole or pi-hole and the negative or electron-rich sites are named sigma-hole bond or pi-hole bond, respectively. The contributions from electrostatic, charge transfer, and other terms or Coulombic interaction to the sigma-hole bond and pi-hole bond were reviewed first followed by a brief discussion on the interplay between the sigma-hole bond and the pi-hole bond as well as application of the two types of noncovalent interactions in the field of anion recognition. It is expected that this review could stimulate further development of the sigma-hole bond and pi-hole bond in theoretical exploration and practical application in the future. PMID- 26886514 TI - Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach. AB - Due to the success of antiretroviral (ART) medications, young people living with perinatally acquired HIV (PHIV+) are now surviving into adolescence and young adulthood. Understanding factors influencing ART non-adherence in this group is important in developing effective adherence interventions. Most studies of ART adherence in HIV-positive populations assess differences in adherence levels and adherence predictors between participants, over a period of time (global adherence). Many individuals living with HIV, however, including PHIV+ young people, take medication inconsistently. To investigate this pattern of adherence, a within-participants design, focussing on specific episodes of adherence and non adherence, is suitable (episodic adherence). A within-participants design was used with 29 PHIV+ young people (17 female, median age 17 years, range 14-22 years), enrolled in the UK Adolescents and Adults Living with Perinatal HIV cohort study. Participants were eligible if they could identify one dose of medication taken and one dose they had missed in the previous two months. For each of the two episodes (one adherent, one non-adherent), behavioural factors (whom they were with, location, routine, day, reminders) and psychological factors at the time of the episode (information about medication, adherence motivation, perceived behavioural skills to adhere to medication - derived from the Information-Motivation-Behavioural Skills (IMB) Model - and affect) were assessed in a questionnaire. Non-adherence was significantly associated with weekend days (Friday to Sunday versus Monday to Thursday, p = .001), lack of routine (p = .004), and being out of the home (p = .003), but not with whom the young person was with or whether they were reminded to take medication. Non adherence was associated with lower levels of behavioural skills (p < .001), and lower positive affect (p = .005). Non-adherence was not significantly associated with negative affect, information about ART, or ART motivation. The use of situationally specific strategies to enhance adherence in young people who take their medication inconsistently is proposed. PMID- 26886516 TI - Micro-RNA-208a, -208b, and -499 as Biomarkers for Myocardial Damage After Cardiac Surgery in Children. AB - OBJECTIVES: To test the hypothesis that cardiac-enriched micro-RNAs can serve as accurate biomarkers that reflect myocardial injury and to predict the postoperative course following pediatric cardiac surgery. Micro-RNAs have emerged as plasma biomarkers for many pathologic states. We aimed to quantify preoperative and postoperative plasma levels of cardiac-enriched micro-RNA-208a, 208b, and -499 in children undergoing cardiac surgery and to evaluate correlations between their levels, the extent of myocardial damage, and the postoperative clinical course. DESIGN: PICU. PATIENTS: Thirty pediatric patients that underwent open heart surgery for the correction of congenital heart defects between January 2012 to July 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At 12 hours post surgery, the plasma levels of the micro-RNAs increased by 300- to 4,000-fold. At 24 hours, their levels decreased but remained significantly higher than before surgery. Micro-RNA levels were associated with troponin levels, longer cardiopulmonary bypass and aortic crossclamp times, maximal postoperative aspartate aminotransferase levels, and delayed hospital discharge. CONCLUSIONS: Circulating micro-RNA-208a, -208b, and -499 are detectable in the plasma of children undergoing cardiac surgery and may serve as novel biomarkers for monitoring and forecasting postoperative myocardial injury and recovery. PMID- 26886517 TI - Neurotrophic growth factor responses to lower body resistance training in older adults. AB - Resistance exercise is an efficacious stimulus for improving cognitive function in older adults, which may be mediated by the upregulation of blood-borne neurotrophic growth factors (NTFs) like brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). However, the NTF response to resistance exercise and training in older adults is poorly understood. Therefore, the purpose of this study was to characterize the timing and magnitude of the NTF response following an acute bout of resistance exercise before and after 8 weeks of resistance training. Ten cognitively normal, older adults (ages 60-77 years, five men) were examined. The acute NTF response to resistance exercise was assessed via serum samples drawn at designated time points following exercise. This procedure was then repeated following 8 weeks of resistance training. BDNF increased immediately post-exercise (Delta9% pre-training, Delta11% post training) then returned to resting levels while IGF-1 remained stable following resistance exercise before and after 8 weeks of resistance training. Basal levels of both NTFs were unaffected by the 8 week training period. We report a transient increase in serum BDNF following a bout of resistance exercise in older adults, which could have implications for the design of interventions seeking to maximize cognitive function in older adults. PMID- 26886518 TI - How Employers Are Responding to the ACA. PMID- 26886519 TI - Asymmetric Thinking about Return on Investment. PMID- 26886520 TI - The Doctor's New Dilemma. PMID- 26886523 TI - Statin-Associated Autoimmune Myopathy. PMID- 26886524 TI - IMAGES IN CLINICAL MEDICINE. Geographic Tongue. PMID- 26886525 TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 5-2016. A 43-Year-Old Man with Altered Mental Status and a History of Alcohol Use. PMID- 26886526 TI - Establishing a Framework--Does Testosterone Supplementation Help Older Men? PMID- 26886522 TI - Clinical Management of Ebola Virus Disease in the United States and Europe. AB - BACKGROUND: Available data on the characteristics of patients with Ebola virus disease (EVD) and clinical management of EVD in settings outside West Africa, as well as the complications observed in those patients, are limited. METHODS: We reviewed available clinical, laboratory, and virologic data from all patients with laboratory-confirmed Ebola virus infection who received care in U.S. and European hospitals from August 2014 through December 2015. RESULTS: A total of 27 patients (median age, 36 years [range, 25 to 75]) with EVD received care; 19 patients (70%) were male, 9 of 26 patients (35%) had coexisting conditions, and 22 (81%) were health care personnel. Of the 27 patients, 24 (89%) were medically evacuated from West Africa or were exposed to and infected with Ebola virus in West Africa and had onset of illness and laboratory confirmation of Ebola virus infection in Europe or the United States, and 3 (11%) acquired EVD in the United States or Europe. At the onset of illness, the most common signs and symptoms were fatigue (20 patients [80%]) and fever or feverishness (17 patients [68%]). During the clinical course, the predominant findings included diarrhea, hypoalbuminemia, hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia; 14 patients (52%) had hypoxemia, and 9 (33%) had oliguria, of whom 5 had anuria. Aminotransferase levels peaked at a median of 9 days after the onset of illness. Nearly all the patients received intravenous fluids and electrolyte supplementation; 9 (33%) received noninvasive or invasive mechanical ventilation; 5 (19%) received continuous renal-replacement therapy; 22 (81%) received empirical antibiotics; and 23 (85%) received investigational therapies (19 [70%] received at least two experimental interventions). Ebola viral RNA levels in blood peaked at a median of 7 days after the onset of illness, and the median time from the onset of symptoms to clearance of viremia was 17.5 days. A total of 5 patients died, including 3 who had respiratory and renal failure, for a mortality of 18.5%. CONCLUSIONS: Among the patients with EVD who were cared for in the United States or Europe, close monitoring and aggressive supportive care that included intravenous fluid hydration, correction of electrolyte abnormalities, nutritional support, and critical care management for respiratory and renal failure were needed; 81.5% of these patients who received this care survived. PMID- 26886521 TI - Effects of Testosterone Treatment in Older Men. AB - BACKGROUND: Serum testosterone concentrations decrease as men age, but benefits of raising testosterone levels in older men have not been established. METHODS: We assigned 790 men 65 years of age or older with a serum testosterone concentration of less than 275 ng per deciliter and symptoms suggesting hypoandrogenism to receive either testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials--the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial. The primary outcome of each of the individual trials was also evaluated in all participants. RESULTS: Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age. The increase in testosterone levels was associated with significantly increased sexual activity, as assessed by the Psychosexual Daily Questionnaire (P<0.001), as well as significantly increased sexual desire and erectile function. The percentage of men who had an increase of at least 50 m in the 6-minute walking distance did not differ significantly between the two study groups in the Physical Function Trial but did differ significantly when men in all three trials were included (20.5% of men who received testosterone vs. 12.6% of men who received placebo, P=0.003). Testosterone had no significant benefit with respect to vitality, as assessed by the Functional Assessment of Chronic Illness Therapy-Fatigue scale, but men who received testosterone reported slightly better mood and lower severity of depressive symptoms than those who received placebo. The rates of adverse events were similar in the two groups. CONCLUSIONS: In symptomatic men 65 years of age or older, raising testosterone concentrations for 1 year from moderately low to the mid-normal range for men 19 to 40 years of age had a moderate benefit with respect to sexual function and some benefit with respect to mood and depressive symptoms but no benefit with respect to vitality or walking distance. The number of participants was too few to draw conclusions about the risks of testosterone treatment. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00799617.). PMID- 26886527 TI - Epigenetic Modulators and the New Immunotherapies. PMID- 26886528 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886529 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886530 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886531 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886532 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886533 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886534 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26886535 TI - A Randomized, Controlled Trial of Total Knee Replacement. PMID- 26886536 TI - A Randomized, Controlled Trial of Total Knee Replacement. PMID- 26886537 TI - Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. PMID- 26886538 TI - Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. PMID- 26886539 TI - Emergency Department Visits Related to Dietary Supplements. PMID- 26886540 TI - Emergency Department Visits Related to Dietary Supplements. PMID- 26886541 TI - Drug-Induced Megaloblastic Anemia. PMID- 26886542 TI - Drug-Induced Megaloblastic Anemia. PMID- 26886543 TI - Drug-Induced Megaloblastic Anemia. PMID- 26886544 TI - Cost of Smoking among Homeless Adults. PMID- 26886546 TI - Belatacept and Long-Term Outcomes in Kidney Transplantation. PMID- 26886545 TI - A Randomized, Controlled Trial of Total Knee Replacement. PMID- 26886547 TI - VIDEOS IN CLINICAL MEDICINE. Removal of Foreign Bodies from the Ear and Nose. PMID- 26886548 TI - IMAGES IN CLINICAL MEDICINE. Central Pontine Myelinolysis. PMID- 26886549 TI - Are Diet Preferences Associated to Skulls Shape Diversification in Xenodontine Snakes? AB - Snakes are a highly successful group of vertebrates, within great diversity in habitat, diet, and morphology. The unique adaptations for the snake skull for ingesting large prey in more primitive macrostomatan snakes have been well documented. However, subsequent diversification in snake cranial shape in relation to dietary specializations has rarely been studied (e.g. piscivory in natricine snakes). Here we examine a large clade of snakes with a broad spectrum of diet preferences to test if diet preferences are correlated to shape variation in snake skulls. Specifically, we studied the Xenodontinae snakes, a speciose clade of South American snakes, which show a broad range of diets including invertebrates, amphibians, snakes, lizards, and small mammals. We characterized the skull morphology of 19 species of xenodontine snakes using geometric morphometric techniques, and used phylogenetic comparative methods to test the association between diet and skull morphology. Using phylogenetic partial least squares analysis (PPLS) we show that skull morphology is highly associated with diet preferences in xenodontine snakes. PMID- 26886550 TI - Cytoskeletal Linker Protein Dystonin Is Not Critical to Terminal Oligodendrocyte Differentiation or CNS Myelination. AB - Oligodendrocyte differentiation and central nervous system myelination require massive reorganization of the oligodendrocyte cytoskeleton. Loss of specific actin- and tubulin-organizing factors can lead to impaired morphological and/or molecular differentiation of oligodendrocytes, resulting in a subsequent loss of myelination. Dystonin is a cytoskeletal linker protein with both actin- and tubulin-binding domains. Loss of function of this protein results in a sensory neuropathy called Hereditary Sensory Autonomic Neuropathy VI in humans and dystonia musculorum in mice. This disease presents with severe ataxia, dystonic muscle and is ultimately fatal early in life. While loss of the neuronal isoforms of dystonin primarily leads to sensory neuron degeneration, it has also been shown that peripheral myelination is compromised due to intrinsic Schwann cell differentiation abnormalities. The role of this cytoskeletal linker in oligodendrocytes, however, remains unclear. We sought to determine the effects of the loss of neuronal dystonin on oligodendrocyte differentiation and central myelination. To address this, primary oligodendrocytes were isolated from a severe model of dystonia musculorum, Dstdt-27J, and assessed for morphological and molecular differentiation capacity. No defects could be discerned in the differentiation of Dstdt-27J oligodendrocytes relative to oligodendrocytes from wild-type littermates. Survival was also compared between Dstdt-27J and wild-type oligodendrocytes, revealing no significant difference. Using a recently developed migration assay, we further analysed the ability of primary oligodendrocyte progenitor cell motility, and found that Dstdt-27J oligodendrocyte progenitor cells were able to migrate normally. Finally, in vivo analysis of oligodendrocyte myelination was done in phenotype-stage optic nerve, cerebral cortex and spinal cord. The density of myelinated axons and g-ratios of Dstdt-27J optic nerves was normal, as was myelin basic protein expression in both cerebral cortex and spinal cord. Together these data suggest that, unlike Schwann cells, oligodendrocytes do not have an intrinsic requirement for neuronal dystonin for differentiation and myelination. PMID- 26886552 TI - Mini-laparoscopic sacrocolpopexy for apical and posterior female pelvic organ prolapse. AB - AIM OF THE VIDEO: Mini-laparoscopic surgery is the future for most laparoscopic procedures. Although already applied in some gynaecological surgical interventions, this video is to our knowledge the first publication on the use of the mini-laparoscopic approach to sacrocolpopexy for apical and posterior pelvic organ prolapse following total hysterectomy. METHODS: The concept of mini laparoscopic sacrocolpopexy presented in this video article was performed on 12 women with post-hysterectomy apical and posterior pelvic organ prolapse using mini-laparoscopic instruments and ports of 3 mm in diameter combined with a 12-mm umbilical port. Surgery was performed with the same principles as for the conventional laparoscopic procedure. RESULTS: The mean operating time was 70 min (SD +/- 12). The tensile strength of the mini-laparoscopic instruments allowed appropriate manipulation of tissue consistent with that of conventional instruments. No difficulties or complications were experienced in comparison to a conventional technique. All patients were discharged from hospital on day 1 postoperatively. CONCLUSIONS: The effectiveness, safety and feasibility of the mini-laparoscopic surgical technique was applied to sacrocolpopexy. Because of the initial favourable experience, the mini-laparoscopic sacrocolpopexy could become more widely used in the future. PMID- 26886551 TI - Mathematical Model of the Firefly Luciferase Complementation Assay Reveals a Non Linear Relationship between the Detected Luminescence and the Affinity of the Protein Pair Being Analyzed. AB - The firefly luciferase complementation assay is widely used as a bioluminescent reporter technology to detect protein-protein interactions in vitro, in cellulo, and in vivo. Upon the interaction of a protein pair, complemented firefly luciferase emits light through the adenylation and oxidation of its substrate, luciferin. Although it has been suggested that kinetics of light production in the firefly luciferase complementation assay is different from that in full length luciferase, the mechanism behind this is still not understood. To quantitatively understand the different kinetics and how changes in affinity of a protein pair affect the light emission in the assay, a mathematical model of the in vitro firefly luciferase complementation assay was constructed. Analysis of the model finds that the change in kinetics is caused by rapid dissociation of the protein pair, low adenylation rate of luciferin, and increased affinity of adenylated luciferin to the enzyme. The model suggests that the affinity of the protein pair has an exponential relationship with the light detected in the assay. This relationship causes the change of affinity in a protein pair to be underestimated. This study underlines the importance of understanding the molecular mechanism of the firefly luciferase complementation assay in order to analyze protein pair affinities quantitatively. PMID- 26886553 TI - Voiding trial outcome following pelvic floor repair without incontinence procedures. AB - INTRODUCTION AND HYPOTHESIS: Our aim was to identify predictors of postoperative voiding trial failure among patients who had a pelvic floor repair without a concurrent incontinence procedure in order to identify low-risk patients in whom postoperative voiding trials may be modified. METHODS: We conducted a retrospective cohort study of women who underwent pelvic floor repair without concurrent incontinence procedures at two institutions from 1 November 2011 through 13 October 2013 after abstracting demographic and clinical data from medical records. The primary outcome was postoperative retrograde voiding trial failure. We used modified Poisson regression to calculate the risk ratio (RR) and 95 % confidence interval (CI). RESULTS: Of the 371 women who met eligibility criteria, 294 (79.2 %) had complete data on the variables of interest. Forty nine (16.7 %) failed the trial, and those women were less likely to be white (p = 0.04), more likely to have had an anterior colporrhaphy (p = 0.001), and more likely to have had a preoperative postvoid residual (PVR) >=150 ml (p = 0.001). After adjusting for race, women were more likely to fail their voiding trial if they had a preoperative PVR of >=150 ml (RR: 1.9; 95 % CI: 1.1-3.2); institution also was associated with voiding trial failure (RR: 3.0; 95 % CI: 1.6-5.4). CONCLUSIONS: Among our cohort, postoperative voiding trial failure was associated with a PVR of >=150 ml and institution at which the surgery was performed. PMID- 26886554 TI - Incidence and risk factors for mesh erosion after laparoscopic repair of pelvic organ prolapse by lateral suspension with mesh. AB - INTRODUCTION AND HYPOTHESIS: The objective of our study was to estimate the incidence and identify the risk factors for mesh erosion after laparoscopic repair of pelvic organ prolapse (POP) by lateral suspension with mesh. METHODS: We conducted a nested case-control study among 480 women who underwent POP repair by laparoscopic lateral suspension with mesh from January 2004 to October 2012. Cases (n = 18) were women who showed mesh erosion following the first intervention through December 2014. Controls (n = 133) were women randomly selected from the same cohort who did not have any erosion. RESULTS: The risk of mesh erosion was 3.8 % with a mean follow-up of 82.3 months (range 28.2 - 130.6 months). The main risk factor was the use of a type 3 mesh (macroporous with either multifilamentous or microporous components) rather than a type 1 mesh (macroporous and monofilamentous; adjusted OR 13.0, 95 % CI 1.5 - 110.6; P = 0.02). Risk factors included smoking (adjusted OR 10.4, 95 % CI 2.3 - 46.5; P < 0.01) and posterior mesh placement (adjusted OR 5.1, 95 % CI 1.2 - 21.8 P = 0.03). CONCLUSIONS: The risk of mesh erosion is low and may be further reduced by using the appropriate mesh material, and by identifying specific patient characteristics such as tobacco use. As conventional vaginal surgery is effective for the treatment of the posterior compartment, the use of posterior mesh during laparoscopic pelvic floor repair needs to be questioned. PMID- 26886556 TI - Metal Nickel Foam as an Efficient and Stable Electrode for Hydrogen Evolution Reaction in Acidic Electrolyte under Reasonable Overpotentials. AB - Acidic electrolytes are advantageous for water electrolysis in the production of hydrogen as there is a large supply of H(+) ions in the solution. In this study, with the applied overpotential larger than the equilibrium potential of Ni(0)/Ni(2+), Ni foam as HER electrode exhibits excellent and stable HER activity with an onset potential of -84 mV (vs RHE), a high current density of 10 mA cm( 2) at -210 mV (vs RHE), and prominent electrochemical durability (longer than 5 days) in acidic electrolyte. The results presented herein may has potential large scale application in hydrogen energy production. PMID- 26886557 TI - A Rotifer-Based Technique to Rear Zebrafish Larvae in Small Academic Settings. AB - Raising zebrafish from larvae to juveniles can be laborious, requiring frequent water exchanges and continuous culturing of live feed. This task becomes even more difficult for small institutions that do not have access to the necessary funding, equipment, or personnel to maintain large-scale systems usually employed in zebrafish husbandry. To open this opportunity to smaller institutions, a cost efficient protocol was developed to culture Nannochloropsis to feed the halophilic, planktonic rotifer Brachionus plicatilis; the rotifers were then used to raise larval zebrafish to juveniles. By using these methods, small institutions can easily raise zebrafish embryos in a cost-efficient manner without the need to establish an extensive fish-raising facility. In addition, culturing rotifers provides a micrometazoan that serves as a model organism for teaching and undergraduate research studies for a variety of topics, including aging, toxicology, and predator-prey dynamics. PMID- 26886555 TI - Pharmacological methods for the preclinical assessment of therapeutics for OAB: an up-to-date review. AB - INTRODUCTION: Licenced oral pharmacotherapies for overactive bladder (OAB) act on muscarinic receptors or beta3-adrenoceptors. The search for new drugs to treat OAB that have novel mechanisms of action is very active, with the aim of discovering more effective and/or better tolerated agents. METHODS: A literature review of the most frequently used pharmacological methods for the preclinical assessment of new agents aimed at treating OAB, such as isolated organ technique, electrophysiological techniques, radioligand binding assay, and animal models, was carried out. Novel potential developments based on recent knowledge of urothelial and neural mechanisms are also discussed. RESULTS: The isolated organ technique, electrophysiological techniques, and the radioligand binding assay are very effective methods for the demonstration that a novel pharmacological target with a specific and high affinity binding site for a new drug is present in the bladder and its modulation regulates functions critical for the pathophysiology of OAB. Afterward, the new drug should be shown to be effective in animal models of OAB, although the translational value of these models is limited by a poor pathophysiological relationship with human OAB. Exciting novel perspectives focusing in particular on the theory of the mucosal-bladder network have recently opened new paths in the discovery and assessment of new therapeutics in this field. CONCLUSIONS: Available experimental models still play a central role in the appraisal of OAB therapeutics; however, their shortcomings and the paucity of very effective drugs indicate the need for new models that better reproduce the pathophysiological features of OAB. Some emerging lines of research show promise. A change of perspective in the future evaluation of putative drugs is required, especially in the light of the latest knowledge on the key role of the mucosal bladder network and the brain-bladder neural pathways. PMID- 26886558 TI - Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model. AB - Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1 weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2 weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2 weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and characterization in single liver MRI sections. PMID- 26886560 TI - Erratum to: CXCL13-CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis. PMID- 26886559 TI - Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons. AB - The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease. PMID- 26886561 TI - Subsequent risk of gout for women with hypertensive disorders in pregnancy: a retrospective cohort study. AB - BACKGROUND: The association between the risk of subsequent gout and hypertensive disorders in pregnancy (HDP), including gestational hypertension and preeclampsia has not been well investigated. We investigated the risk of gout in later life for women with a history of HDP. METHODS: We identified 1133 newly diagnosed HDP women aged 14-40 years from Taiwan insurance claims data from the period of 2000 2010. From the same database, 9064 women without HDP were randomly selected as the control cohort, with frequency matched by age and diagnosis year. Those with a baseline history of hypertension or gout were excluded from this study. All study participants were followed until the development of gout, withdrawal from the insurance program, or the end of 2011. Cox proportional hazards regression was used to assess the risk for gout in the HDP cohort compared with the controls. RESULTS: The incidence of gout was 2.83 folds higher in the HDP cohort than in the control cohort (2.66 vs. 0.94 per 1000 person-years) with an adjusted hazard ratio of 2.34 (95% confidence interval = 1.36-4.02) and 1.84 (95% confidence interval = 1.03-3.32) after controlling for comorbidities prior to and after pregnancy, respectively. In addition, the risk for gout increased as the severity of HDP increased. CONCLUSION: Women with HDP are at higher risk of developing gout in their later life. Close surveillance for hyperuricemia and lifestyle intervention should be considered for these high risk women. Further prospective study is needed for investigating the relationship between HDP and subsequent gout. PMID- 26886562 TI - A functional variant in the coding region of CAMTA2 is associated with left ventricular hypertrophy by affecting the activation of Nkx2.5-dependent transcription. AB - OBJECTIVE: The calmodulin-binding transcription activator 2 (CAMTA2) promotes transcription of genes involved in cardiac hypertrophy through its interaction with Nkx2.5 and is an indispensable transcription coactivator for cardiac hypertrophy. We hypothesized that variants in the coding region of CAMTA2 would affect its function and confer a risk of cardiac hypertrophy. METHODS: The effects of the variant rs238234 on the activity of the atrial natriuretic factor promoter and on the cardiomyocytes hypertrophy were assessed in the H9C2 cell line and primary neonatal rat cardiomyocytes, respectively. Furthermore, the association of this variant with left ventricular hypertrophy (LVH) was tested in hypertensive patients with and without hypertrophy (N = 325 and 697), and this analysis was replicated in an independent population of 987 hypertensive patients without hypertrophy and 463 hypertensive patients with hypertrophy. RESULTS: We found that the G allele of rs238234 activated the atrial natriuretic factor promoter more strongly than the C allele. The cell size of cardiomyocytes was larger in the presence of the Ad-CAMTA2 G allele, and the G allele was associated with significantly increased susceptibility to LVH in hypertensive [odds ratio (OR), 1.29; P = 0.009]. In the discovery cohort, after adjusting for age and sex, the GG genotype was significantly associated with increased LVH risk (OR, 1.75; P = 0.015). There was little attenuation of the ORs (1.62; P < 0.05) when adjusting for BMI, heart rate, blood pressure, smoking, and drinking and further adjusting all covariates including lipid levels and other major risk factors. However, the GC genotype did not show any association with LVH using three regressive models. Replication in the second study yielded similar results. CONCLUSION: Our results provide evidence that the rs238234 GG genotype in the coding region of CAMTA2 may increase the risk of LVH by affecting the activation of Nkx2.5-dependent transcription. PMID- 26886563 TI - Tripartite motif-containing 55 identified as functional candidate for spontaneous cardiac hypertrophy in the rat locus cardiac mass 22. AB - BACKGROUND: Left ventricular (LV) hypertrophy is a risk factor for cardiovascular death, but the genetic factors determining LV size and predisposition to hypertrophy are not well understood. We have previously linked the quantitative trait locus cardiac mass 22 (Cm22) on chromosome 2 with cardiac hypertrophy independent of blood pressure in the spontaneously hypertensive rat. From an original cross of spontaneously hypertensive rat with F344 rats, we derived a normotensive polygenic model of spontaneous cardiac hypertrophy, the hypertrophic heart rat (HHR) and its control strain, the normal heart rat (NHR). METHODS AND RESULTS: To identify the genes and molecular mechanisms underlying spontaneous LV hypertrophy we sequenced the HHR genome with special focus on quantitative trait locus Cm22. For correlative analyses of function, we measured global RNA transcripts in LV of neonatal HHR and NHR and 198 neonatal rats of an HHR * NHR F2 crossbred population. Only one gene within locus Cm22 was differentially expressed in the parental generation: tripartite motif-containing 55 (Trim55), with mRNA downregulation in HHR (P < 0.05) and reduced protein expression. Trim55 mRNA levels were negatively correlated with LV mass in the F2 cross (r = -0.16, P = 0.025). In exon nine of Trim55 in HHR, we found one missense mutation that functionally alters protein structure. This mutation was strongly associated with Trim55 mRNA expression in F2 rats (F = 10.35, P < 0.0001). Similarly, in humans, we found reduced Trim55 expression in hearts of subjects with idiopathic dilated cardiomyopathy. CONCLUSION: Our study suggests that the Trim55 gene, located in Cm22, is a novel candidate gene for polygenic LV hypertrophy independent of blood pressure. PMID- 26886564 TI - Urinary sodium excretion predicts blood pressure response to spironolactone in patients with resistant hypertension independent of aldosterone status. AB - OBJECTIVE: Resistant hypertension (RHTN), blood pressure (BP) at least 140/90 mmHg despite using at least three different medications, including a diuretic, is associated with high dietary sodium and hyperaldosteronism. Mineralocorticoid receptor antagonists are recommended for treatment of RHTN, however, BP response to these agents varies widely. In the current analysis, we assessed predictors of BP response to spironolactone in patients with RHTN. METHODS: We retrospectively evaluated the BP response to adding spironolactone 12.5-25 mg to existing medications. A favorable BP response was defined as a reduction in SBP of at least 10 mmHg. Tested variables included baseline characteristics and biochemical parameters. RESULTS: A total of 79 patients with RHTN were included in the analysis. Evaluated patients were more likely women (53.2%) and African-American (55.8%); were generally obese (76%) and were prescribed an average of four antihypertensive medications. Baseline SBP was 153.6 +/- 22.3 mmHg; addition of spironolactone resulted in a mean reduction of 15.5 +/- 20.7 mmHg. Patients with high urinary sodium excretion (>=200 mEq/24 h) had a significantly greater BP reduction compared with patients with normal excretion (<200 mEq/24 h) (P = 0.008). Multivariable analysis identified 24 h urinary sodium excretion as a significant predictor of BP response (P = 0.021) after controlling for potential confounders, including primary aldosteronism. CONCLUSION: The antihypertensive effect of spironolactone is positively related to urinary sodium excretion regardless of aldosterone status. These findings suggest that mineralocorticoid receptor antagonists may be of preferential benefit in counteracting the BP effects of high dietary sodium. PMID- 26886565 TI - Diuretic antihypertensive drugs and incident dementia risk: a systematic review, meta-analysis and meta-regression of prospective studies. AB - OBJECTIVE: Diuretic drugs have been a mainstay of hypertension treatment in the elderly however their dementia sparing effects are under-reported. The objective was to quantify dementia risk in relation to diuretic antihypertensive drugs. METHODS: Electronic databases were searched until June 2015. ELIGIBILITY CRITERIA: population, adults without dementia from primary care, community cohort, residential/institutionalized, or randomized controlled trial; exposure, diuretic antihypertensive drug; comparison, no diuretic drug, other or no antihypertensive drug, placebo-control; outcome, incident dementia diagnosed by standardized criteria. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled in fixed-effects models with RevMan 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) and the findings rated according to The Grading of Recommendations Assessment, Development and Evaluation criteria. RESULTS: A total of 15 articles were included (52 599 persons, 3444 dementia cases, median age 76.1 years) and median follow-up was 6.1 years. Diuretics were associated with reduced dementia risk (HR 0.83; 95% CI 0.76-0.91, P < 0.0001, I = 0) and Alzheimer's disease risk (HR 0.82; 95% CI 0.71-0.94, P = 0.004, I = 0). Stratified analysis indicated a difference between potassium sparing, thiazide and loop diuretics (P = 0.01). Risk estimates were generally consistent comparing monotherapy vs. combination therapy, study design and follow-up. Meta-regression showed that demographics, stroke, heart failure, diabetes, liver disease, attrition, mortality rate, cognitive function, and apolipoprotein E allele did not moderate the results. CONCLUSION: Diuretic antihypertensive drugs were associated with a consistent reduction in dementia risk without heterogeneity, pointing to generalizability of these findings. REGISTRATION: PROSPERO [CRD42015023428]. PMID- 26886566 TI - Prevalence and prognosis of ECG abnormalities in normotensive and hypertensive individuals. AB - OBJECTIVE: To define the prevalence and prognosis of ECG abnormalities in hypertensive individuals. METHODS: ECG, blood pressure and other cardiovascular risk factors were recorded in a nationwide population sample of 5800 Finns. The presence of 15 ECG abnormalities was evaluated. Participants were divided into categories by blood pressure and followed for coronary heart (CHD) and cardiovascular disease (CVD) events. RESULTS: Mean follow-up was 10.4 +/- 2.2 years. The age- and sex-adjusted prevalence rates of ECG abnormalities were generally higher in the hypertensive participants than in normotensive individuals. In multivariable-adjusted Cox models, the following ECG abnormalities predicted CHD in hypertensive participants: left ventricular hypertrophy (LVH) by Sokolow-Lyon criteria [hazard ratio, 1.47; 95% confidence interval (CI), 1.07-2.01; P = 0.02], LVH with ST-depression and negative T wave (ST/T changes) (hazard ratio, 2.31; 95% CI, 1.20-4.43, P = 0.01), ST/T changes (hazard ratio, 2.12; 95% CI, 1.34-3.36; P = 0.001), positive T wave in lead aVR (AVRT+) (hazard ratio, 1.74; 95% CI, 1.15-2.64; P = 0.009) and poor R-wave progression (hazard ratio, 2.02; 95% CI, 1.27-3.22; P = 0.003). These ECG abnormalities were also significant predictors of CVD in hypertensive participants (P <= 0.03 for all). Nonspecific intraventricular conduction delay predicted CVD in the whole population (hazard ratio, 1.50; 95% CI, 1.06-2.13; P = 0.02). Prolonged QT interval, abnormal P-wave indices, left axis deviation and early repolarization pattern were not associated with CHD or CVD. CONCLUSION: ECG abnormalities are highly prevalent in hypertensive individuals. LVH is still the cornerstone of cardiovascular risk assessment in hypertensive patients. The additional assessment of ST/T changes, AVRT+ and poor R-wave progression in ECGs could improve risk prediction in hypertensive patients. PMID- 26886567 TI - Centrally acting drug moxonidine decreases reactive oxygen species via inactivation of the phosphoinositide-3 kinase signaling in the rostral ventrolateral medulla in hypertensive rats. AB - OBJECTIVE: Centrally acting antihypertensive action of moxonidine is a result of activation of Imidazoline-1 receptor (I1R) in the rostral ventrolateral medulla (RVLM). Hypertension shows an increase in reactive oxygen species (ROS) in the RVLM. The present objective was to determine the phosphoinositide-3 kinase (PI3K) signaling pathway involved in the effect of moxonidine on ROS generation in the RVLM of spontaneously hypertensive rat (SHR). METHODS: Wistar-Kyoto rats and SHR received intracisternal infusion (2 weeks) of tested agents which were subjected to subsequent experiments. In-situ ROS in the RVLM was evaluated by the oxidative fluorescence dye. Western blot and PCR analysis were performed to detect the expression levels of PI3K signaling pathway. Lentivirus was injected bilaterally into the RVLM for silencing PI3K signaling. RESULTS: ROS production in the RVLM was dose-dependently reduced in SHRs treated with infusion of moxonidine (20 nmol/day), which was prevented by the I1R antagonist efaroxan but not by the alpha2-adrenoceptor antagonist yohimbine. Moxonidine pretreatment significantly blunted cardiovascular sensitivity to injection of tempol (5 nmol) or angiotensin II (10 pmol) into the RVLM in SHR. Expression levels of PI3K/Akt, nuclear factor kappa-B (NFkappaB), NADPHase (NOX4), and angiotensin type I receptor (AT1R) in the RVLM were markedly decreased in SHR treated with moxonidine. Infection of lentivirus containing PI3K shRNA in the RVLM effectively prevented effects of moxonidine on cardiovascular activity and expression levels of Akt, NFkappaB, NOX4, and AT1R. CONCLUSION: The centrally antihypertensive drug moxonidine decreases ROS production in the RVLM through inactivation of the PI3K/Akt signaling pathway in hypertension. PMID- 26886569 TI - Gold vs Rhodium Catalysis: Tuning Reactivity through Catalyst Control in the C-H Alkynylation of Isoquinolones. AB - A site-selective C-4/C-8 alkynylation of isoquinolones catalyzed by gold and rhodium complexes is reported. A broad range of synthetically useful functional groups (-F, -Cl, -Br, -CF3, -OMe, alkyl, etc.) were tolerated, providing an efficient and robust protocol for the synthesis either C-4- or C-8-alkynylated isoquinolones. PMID- 26886570 TI - A systematic review on the long-term success of calcium phosphate plasma-spray coated dental implants. AB - The objectives of the current review were (1) to systematically appraise, and (2) to evaluate long-term success data of calcium phosphate (CaP) plasma-spray-coated dental implants in clinical trials with at least 5 years of follow-up. To describe the long-term efficacy of functional implants, the outcome variables were (a) percentage annual complication rate (ACR) and (b) cumulative success rate (CSR), as presented in the selected articles. The electronic search yielded 645 titles. On the basis of the inclusion criteria, 8 studies were finally included. The percentage of implants in function after the first year was estimated to be 98.4 % in the maxilla and 99.2 % in the mandible. The estimates of the weighted mean ACR-percentage increased over the years up to 2.6 (SE 0.7) during the fifth year of function for the maxilla and to 9.4 (SE 8.4) for the mandible in the tenth year of function. After 10 years, the mean percentage of successful implants was estimated to be 71.1 % in the maxilla and 72.2 % in the mandible. The estimates seem to confirm the proposed, long-term progressive bone loss pattern of CaP-ceramic-coated dental implants. Within the limits of this meta-analytic approach to the literature, we conclude that: (1) published long term success data for calcium phosphate plasma-spray-coated dental implants are limited, (2) comparison of the data is difficult due to differences in success criteria among the studies, and (3) long-term CSRs demonstrate very weak evidence for progressive complications around calcium phosphate plasma-spray-coated dental implants. PMID- 26886571 TI - An accurate bimaxillary repositioning technique using straight locking miniplates for the mandible-first approach in bimaxillary orthognathic surgery. AB - Bimaxillary orthognathic surgery has been widely performed to achieve optimal functional and esthetic outcomes in patients with dentofacial deformity. Although Le Fort I osteotomy is generally performed before bilateral sagittal split osteotomy (BSSO) in the surgery, in several situations BSSO should be performed first. However, it is very difficult during bimaxillary orthognathic surgery to maintain an accurate centric relation of the condyle and decide the ideal vertical dimension from the skull base to the mandible. We have previously applied a straight locking miniplate (SLM) technique that permits accurate superior maxillary repositioning without the need for intraoperative measurements in bimaxillary orthognathic surgery. Here we describe the application of this technique for accurate bimaxillary repositioning in a mandible-first approach where the SLMs also serve as a condylar positioning device in bimaxillary orthognathic surgery. PMID- 26886572 TI - Nanoscaled Zinc Pyrazolate Metal-Organic Frameworks as Drug-Delivery Systems. AB - This work describes synthesis at the nanoscale of the isoreticular metal-organic framework (MOF) series ZnBDP_X, based on the assembly of Zn(II) metal ions and the functionalized organic spacers 1,4-bis(1H-pyrazol-4-yl)-2-X-benzene (H2BDP_X; X = H, NO2, NH2, OH). The colloidal stability of these systems was evaluated under different relevant intravenous and oral-simulated physiological conditions, showing that ZnBDP_OH nanoparticles exhibit good structural and colloidal stability probably because of the formation of a protein corona on their surface that prevents their aggregation. Furthermore, two antitumor drugs (mitroxantrone and [Ru(p-cymene)Cl2(pta)] (RAPTA-C) where pta = 1,3,5-triaza-7-phospaadamantane) were encapsulated within the pores of the ZnBDP_X series in order to investigate the effect of the framework functionalization on the incorporation/delivery of bioactive molecules. Thus, the loading capacity of both drugs within the ZnBDP_X series seems to directly depend on the surface area of the solids. Moreover, ligand functionalization significantly affects both the delivery kinetics and the total amount of released drug. In particular, ZnBDP_OH and ZnBDP_NH2 matrixes show a slower rate of delivery and higher percentage of release than ZnBDP_NO2 and ZnBDP_H systems. Additionally, RAPTA-C delivery from ZnBDP_OH is accompanied by a concomitant and progressive matrix degradation due to the higher polarity of the BPD_OH ligand, highlighting the impact of functionalization of the MOF cavities over the kinetics of delivery. PMID- 26886573 TI - Molecular Cloning and Characterization of Hydroperoxide Lyase Gene in the Leaves of Tea Plant (Camellia sinensis). AB - Hydroperoxide lyase (HPL, E.C. 4.1.2.) is the major enzyme in the biosynthesis of natural volatile aldehydes and alcohols in plants, however, little was known about HPL in tea plants (Camellia sinensis). A unique cDNA fragment was isolated by suppressive subtractive hybridization (SSH) from a tea plant subjected to herbivory by tea geometrid Ectropis obliqua. This full length cDNA acquired by RACE was 1476 bp and encoded 491 amino acids. DNA and protein BLAST searches showed high homology to HPL sequences from other plants. The His-tag expression vector pET-32a(+)/CsHPL was constructed and transferred into Escherichia coli Rosetta (DE3). The expression product of recombinant CsHPL in E. coli was about 60 kDa. The enzyme activity of CsHPL was 0.20 MUmol.min(-1).mg(-1). Quantitative RT-PCR analysis indicated CsHPL was strongly up-regulated in tea plants after Ectropis obliqua attack, suggesting that it may be an important candidate for defense against insects in tea plants. PMID- 26886574 TI - Privacy and confidentiality measures in genetic testing and counselling: arguing on genetic exceptionalism again? AB - Medical confidentiality in clinical genetics poses an important question about its scope, which would be in line with professional ethics and simple honesty. It is already known that the maintenance of absolute anonymity, bearing in mind the current progress of genetic techniques, is virtually impossible. On the other hand, our insight into the information contained in the human genome is increasing. This mini-review presents the authors' standpoint regarding this complex and difficult issue. PMID- 26886575 TI - Intrusive thoughts: linking spontaneous mind wandering and OCD symptomatology. AB - One recent line of research in the literature on mind wandering has been concerned with examining rates of mind wandering in special populations, such as those characterized by attention-deficit/hyperactivity disorder, dysphoria, and schizophrenia. To best conceptualize mind wandering in studies examining special populations, it has recently been suggested that researchers distinguish between deliberate and spontaneous subtypes of this experience. Extending this line of research on mind wandering in special populations, in a large non-clinical sample (N = 2636), we examined how rates of deliberate and spontaneous mind wandering vary with symptoms of obsessive-compulsive disorder (OCD). Results indicate that, whereas deliberate mind wandering is not associated with OCD symptomatology, spontaneous mind wandering is, with higher reports of spontaneous mind wandering being associated with higher reports of OCD symptoms. We discuss the implications of these results for understanding both mind wandering and OCD. PMID- 26886576 TI - A Food Effect Study of an Oral Thrombin Inhibitor and Prodrug Approach To Mitigate It. AB - LB30870, a new direct thrombin inhibitor, showed 80% reduction in oral bioavailability in fed state. The present study aims to propose trypsin binding as a mechanism for such negative food effect and demonstrate a prodrug approach to mitigate food effect. Effect of food composition on fed state oral bioavailability of LB30870 was studied in dogs. Various prodrugs were synthesized, and their solubility, permeability, and trypsin binding affinity were measured. LB30870 and prodrugs were subject to cocrystallization with trypsin, and the X-ray structures of cocrystals were determined. Food effect was studied in dogs for selected prodrugs. Protein or lipid meal appeared to affect oral bioavailability of LB30870 in dogs more than carbohydrate meal. Blocking both carboxyl and amidine groups of LB30870 resulted in trypsin Ki values orders of magnitude higher than that of LB30870. Prodrugs belonged to either Biopharmaceutical Classification System I, II, or III. X-ray crystallography revealed that prodrugs did not bind to trypsin, but instead their hydrolysis product at the amidine blocking group formed cocrystal with trypsin. A prodrug with significantly less food effect than LB30870 was identified. Binding of prodrugs to food components such as dietary fiber appeared to counteract the positive effect brought with the prodrug approach. Further formulation research is warranted to enhance the oral bioavailability of prodrugs. In conclusion, this study is the first to demonstrate that the negative food effect of LB30870 can be attributed to trypsin binding. Trypsin binding study is proposed as a screening tool during lead optimization to minimize food effect. PMID- 26886577 TI - Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae. AB - Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress. PMID- 26886579 TI - Unprecedented W2(0) quadruply bonded complex supported by pi-donor ligands. AB - A quadruply bonded complex W2(DippF)2K2 with a W2(0) core was synthesized and structurally characterized. The observed W-W distance of 2.407(1) A and DFT calculations are consistent to the unprecedented electronic structure in D(2h) symmetry of sigma(2)pi(2)pi(2)delta(2)delta(2)delta*(2) where the HOMO is the delta* orbital. PMID- 26886578 TI - The modified lateral supraorbital approach for tumors of the petroclival junction extending into the anterior cerebellopontine area. AB - Various surgical approaches for the removal of meningioma and trigeminal schwannoma in the petroclival junction (PCJ) and anterior cerebellopontine area (CPA) have been described previously. In this study, we compared the surgical outcomes of the combined petrosal approach and a modified lateral supraorbital (MLSO) approach and evaluated the reliability and safety of the MLSO approach. Fifty patients underwent surgical treatment using the combined petrosal or MLSO approach between 1996 and 2011. We retrospectively analyzed the clinical data and compared the two approaches. Among 50 patients, 27 patients underwent operation through the combined petrosal approach and 23 underwent operation through the MLSO approach. The operation time of the MLSO approach was significantly shorter than that of the combined petrosal approach (p = 0.03). There was no significant difference in the gross total resection rate between the two approaches (p = 0.67). After the operation, the improvement in Karnofsky performance score and Mean Glasgow outcomes scales were better in the MLSO approach, but without statistical significance (p = 0.723, p = 0.20 respectively). Complications occurred more often with the combined petrosal approach than with MLSO. Facial nerve palsy was the most common complication, followed by hearing difficulty. The frequency of these two complications was higher in the combined petrosal approach. Various tumors occurring in the PCJ and anterior CPA remain a challenging problem for neurosurgeons. The new modified approach of MLSO yielded good surgical results for these tumors compared to the combined petrosal approach. Therefore, the MLSO approach might be a good option for removal of tumors in the PCJ including anterior CPA. PMID- 26886580 TI - Repository Planning, Design, and Engineering: Part I--Infrastructure. AB - This is a two-part review describing the planning, engineering, and design considerations for building a new repository for biological and environmental samples. Part I addresses the physical infrastructure requirements for a repository; Part II will cover equipment and costing. Planning for construction of a new repository is a complex process requiring comprehensive preplanning and adherence to many regulatory and safety requirements. Guidance and a planning timeline are provided for many of the physical aspects and large capital acquisition costs for the expansion of an existing repository, or the creation of a new repository facility, using an available unoccupied building such as a former warehouse. This article provides a comprehensive set of information about every aspect of repository construction and operation to be considered in the planning process, and also addresses all aspects of designing and constructing a new repository in an existing structure. The engineering and design parameters for the repository are discussed in detail. PMID- 26886581 TI - Water, Water, Everywhere: Defining and Assessing Data Sharing in Academia. AB - Sharing of research data has begun to gain traction in many areas of the sciences in the past few years because of changing expectations from the scientific community, funding agencies, and academic journals. National Science Foundation (NSF) requirements for a data management plan (DMP) went into effect in 2011, with the intent of facilitating the dissemination and sharing of research results. Many projects that were funded during 2011 and 2012 should now have implemented the elements of the data management plans required for their grant proposals. In this paper we define 'data sharing' and present a protocol for assessing whether data have been shared and how effective the sharing was. We then evaluate the data sharing practices of researchers funded by the NSF at Oregon State University in two ways: by attempting to discover project-level research data using the associated DMP as a starting point, and by examining data sharing associated with journal articles that acknowledge NSF support. Sharing at both the project level and the journal article level was not carried out in the majority of cases, and when sharing was accomplished, the shared data were often of questionable usability due to access, documentation, and formatting issues. We close the article by offering recommendations for how data producers, journal publishers, data repositories, and funding agencies can facilitate the process of sharing data in a meaningful way. PMID- 26886582 TI - Carotid atherosclerosis, cytomegalovirus infection, and cognitive decline in the very old: a community-based prospective cohort study. AB - To investigate various risk factors of cognitive decline in the very old, we studied 494 subjects over 85 years old without diagnosis of dementia at baseline from the Tokyo Oldest Old Survey on Total Health, an ongoing, community-based cohort in Japan. Cognitive function was assessed at baseline and at 3-year follow up using Mini-Mental State Examination (MMSE). Plasma samples were assayed for levels of cytomegalovirus (CMV) immunoglobulin G (IgG) antibodies, tumor necrosis factor-alpha, interleukin-6, and blood chemistry. Carotid artery plaques were measured using an ultrasonography. In the cross-sectional analyses using Tobit regression, individuals with high carotid artery plaque score (>=5.0) had MMSE scores that were 1.08 points lower compared to those with no plaque (95 % confidence interval (CI) -1.95 to -0.20; p = 0.016), adjusted for age, sex, and education. Individuals with CMV IgG titers in the highest quartile had MMSE scores that were 1.47 points lower compared to individuals in the lowest quartile (95 % CI -2.44 to -0.50; p = 0.003). CMV and carotid atherosclerosis showed evidence of an interaction, where the association between CMV and MMSE was present only in subjects with carotid artery plaque. In the longitudinal analyses using linear regression, carotid atherosclerosis, smoking, low grip strength, and poor activities of daily living (ADL) status were associated with faster cognitive decline, adjusted for age, sex, education, and baseline cognitive function. Our findings suggest that carotid atherosclerosis is consistently associated with low cognitive function in the very old and modifies the association between latent CMV infection and cognition. PMID- 26886584 TI - The benefit of deep inspiration breath hold: evaluating cardiac radiation exposure in patients after mastectomy and after breast-conserving surgery. AB - BACKGROUND: This study aims to evaluate the reduction of cardiac radiation dose and volume with deep inspiration breath hold (DIBH) technique compared to free breathing (FB) in patients with left-sided breast cancer. The study also aims to evaluate whether the benefits of DIBH vary in patients who had whole breast radiotherapy (RT) after breast-conserving surgery (BCS) and those who had chest wall RT post-mastectomy (M). METHODS: FB and DIBH plans were generated for 15 consecutive post-BCS patients and 17 post-M patients who underwent RT with DIBH using varian real-time position management (RPM) system. Cardiac shields were used in all post-BCS plans, provided that clinical treatment volume coverage was not compromised, while chest wall coverage took priority in post-M plans. The prescribed dose was 50 Gy in 25 fractions for the whole breast or the chest wall. Parameters of interest were cardiac V5, mean LAD dose, maximum LAD dose, and mean heart dose. The impact of DIBH was compared in post-BCS and post-M patients using paired t tests. To gauge clinically meaningful outcome, the proportion of patients with V5 < 5 % and mean cardiac dose <2 Gy were compared using McNemar's test. RESULTS: DIBH decreased V5 by an absolute 4.5 % (2.3 vs. 6.8 %; p < 0.0001) in post-M group, and by an absolute 2.4 % (1.3 vs. 3.7 %; p = 0.0028) in post-BCS group. DIBH decreased the mean heart dose by 107.0 cGy (127.4 vs. 234.4 cGy; p = 0.0002) in post-M group, and by 58.9 cGy (82.2 vs. 141.1 cGy; p = 0.0012) in post BCS group. DIBH decreased mean LAD by 1201.6 cGy (670 vs. 1872.5 cGy; p = 0.0006) in post-M group, and by 799.0 cGy (425.3 vs. 1224.3 cGy; p = 0.0003) in post-BCS group. DIBH also decreased max LAD dose by 1244.3 cGy (2776.0 vs. 4020.3 cGy; p = 0.0014) in post-M group, and by 1856.3 cGy (1898.7 vs. 3754.9 cGy; p = 0.0005) in post-BCS group. In post-BCS group, cardiac V5 < 5 % was achieved in 10/15 (67 %) FB patients, and in 15/15 (100 %) DIBH patients (p = 0.002), and mean heart dose <2 Gy was achieved in 12/15 (80 %) FB patients and in 15/15 (100 %) DIBH patients (p < 0.001). This compares with post-M group, in which V5 < 5 % was achieved in 6/17 (35 %) FB patients and in 16/17 (94 %) DIBH patients (p = 0.05), and mean heart dose <2 Gy was achieved in 7/17 FB (41 %) an 16/17 DIBH patients (94 %) (p = 0.03). CONCLUSION: The results of this study suggest that there is considerable reduction in cardiac exposure in most patients with DIBH compared to FB, although less reduction is observed in the post-BCS patients. The use of cardiac shields and collimators/gantry adjustments, more readily applicable for post-BCS cases, may limit the additional benefits of DIBH. In an environment where DIBH availability is limited, the result of this study supports the preferential use of DIBH in post-M patients over post-BCS patients. PMID- 26886583 TI - Functional and Structural Analysis of a beta-Glucosidase Involved in beta-1,2 Glucan Metabolism in Listeria innocua. AB - Despite the presence of beta-1,2-glucan in nature, few beta-1,2-glucan degrading enzymes have been reported to date. Recently, the Lin1839 protein from Listeria innocua was identified as a 1,2-beta-oligoglucan phosphorylase. Since the adjacent lin1840 gene in the gene cluster encodes a putative glycoside hydrolase family 3 beta-glucosidase, we hypothesized that Lin1840 is also involved in beta 1,2-glucan dissimilation. Here we report the functional and structural analysis of Lin1840. A recombinant Lin1840 protein (Lin1840r) showed the highest hydrolytic activity toward sophorose (Glc-beta-1,2-Glc) among beta-1,2 glucooligosaccharides, suggesting that Lin1840 is a beta-glucosidase involved in sophorose degradation. The enzyme also rapidly hydrolyzed laminaribiose (beta 1,3), but not cellobiose (beta-1,4) or gentiobiose (beta-1,6) among beta-linked gluco-disaccharides. We determined the crystal structures of Lin1840r in complexes with sophorose and laminaribiose as productive binding forms. In these structures, Arg572 forms many hydrogen bonds with sophorose and laminaribiose at subsite +1, which seems to be a key factor for substrate selectivity. The opposite side of subsite +1 from Arg572 is connected to a large empty space appearing to be subsite +2 for the binding of sophorotriose (Glc-beta-1,2-Glc beta-1,2-Glc) in spite of the higher Km value for sophorotriose than that for sophorose. The conformations of sophorose and laminaribiose are almost the same on the Arg572 side but differ on the subsite +2 side that provides no interaction with a substrate. Therefore, Lin1840r is unable to distinguish between sophorose and laminaribiose as substrates. These results provide the first mechanistic insights into beta-1,2-glucooligosaccharide recognition by beta-glucosidase. PMID- 26886585 TI - Red and infrared laser therapy inhibits in vitro growth of major bacterial species that commonly colonize skin ulcers. AB - Low-level laser therapy (LLLT) is used in chronic wounds due to its healing effects. However, bacterial species may colonize these wounds and the optimal parameters for effective bacterial inhibition are not clear. The aim of this study was to analyze the effect of LLLT on bacterial growth in vitro. Bacterial strains including Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were suspended in saline solution at a concentration of 10(3) cells/ml and exposed to laser irradiation at wavelengths of 660, 830, and 904 nm at fluences of 0 (control), 3, 6, 12, 18, and 24 J/cm(2). An aliquot of the irradiated suspension was spread on the surface of petri plates and incubated at 37 degrees C for quantification of colony-forming unit after 24, 48, and 72 h. Laser irradiation inhibited the growth of S. aureus at all wavelengths and fluences higher than 12 J/cm(2), showing a strong correlation between increase in fluence and bacterial inhibition. However, for P. aeruginosa, LLLT inhibited growth at all wavelengths only at a fluence of 24 J/cm(2). E. coli had similar growth inhibition at a wavelength of 830 nm at fluences of 3, 6, 12, and 24 J/cm(2). At wavelengths of 660 and 904 nm, growth inhibition was only observed at fluences of 12 and 18 J/cm(2), respectively. LLLT inhibited bacterial growth at all wavelengths, for a maximum of 72 h after irradiation, indicating a correlation between bacterial species, fluence, and wavelength. PMID- 26886586 TI - Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester. AB - The treatment of Klebsiella pneumoniae, particularly extended-spectrum beta lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5 ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae. PMID- 26886587 TI - Impact of CO2 laser and stannous fluoride on primary tooth erosion. AB - This study evaluated in vitro the effect of input power of CO2 laser, either associated or not to stannous fluoride (SnF2) gel, for the control of intrinsic erosion in primary teeth. One hundred four enamel slabs (3 * 3 * 2 mm) from human primary molars were flattened and polished. Adhesive tapes were placed on their surface leaving a window of 3 * 1 mm. Slabs were then cycled four times in 0.01 M hydrochloric acid (pH 2, 2 min) and in artificial saliva (2 h) for creation of erosive lesions. Specimens were randomly assigned into eight groups (n = 13) according to fluoride application [absent (control) or 0.4% stannous fluoride gel (SnF2)] and input power of CO2 laser [unlased (control), 0.5, 1.0 or 1.5 W]. The CO2 laser irradiation was performed in an ultra-pulse mode (100 MUs of pulse duration), 4-mm working distance, for 10 s. Specimens were then submitted to further erosive episodes for 5 days and evaluated for enamel relative permeability. Fluoride did not show any protective effect for any of the laser treated groups or control (p = 0.185). However, a significant effect was detected for input power of CO2 laser (p = 0.037). Tukey's test showed that there was a significant statistically difference between specimens irradiated with 0.5 and 1.5 W (p = 0.028). The input power of 0.5 W showed lower permeability. Variation of input power CO2 laser can influence enamel permeability, at the power of 1.5 W which promoted greater permeability. PMID- 26886588 TI - Analysis of heterogeneous gallstones using laser-induced breakdown spectroscopy (LIBS) and wavelength dispersive X-ray fluorescence (WD-XRF). AB - Laser-induced breakdown spectroscopy (LIBS) is an emerging analytical technique with numerous advantages such as rapidity, multi-elemental analysis, no specific sample preparation requirements, non-destructiveness, and versatility. It has been proven to be a robust elemental analysis tool attracting interest because of being applied to a wide range of materials including biomaterials. In this paper, we have performed spectroscopic studies on gallstones which are heterogeneous in nature using LIBS and wavelength dispersive X-ray fluorescence (WD-XRF) techniques. It has been observed that the presence and relative concentrations of trace elements in different kind of gallstones (cholesterol and pigment gallstones) can easily be determined using LIBS technique. From the experiments carried out on gallstones for trace elemental mapping and detection, it was found that LIBS is a robust tool for such biomedical applications. The stone samples studied in the present paper were classified using the Fourier transform infrared (FTIR) spectroscopy. WD-XRF spectroscopy has been applied for the qualitative and quantitative analysis of major and trace elements present in the gallstone which was compared with the LIBS data. The results obtained in the present paper show interesting prospects for LIBS and WD-XRF to study cholelithiasis better. PMID- 26886589 TI - Cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser. AB - Low-level infrared laser is considered safe and effective for treatment of muscle injuries. However, the mechanism involved on beneficial effects of laser therapy are not understood. The aim was to evaluate cell viability, reactive oxygen species, apoptosis, and necrosis in myoblast cultures exposed to low-level infrared laser at therapeutic fluences. C2C12 myoblast cultures at different (2 and 10 %) fetal bovine serum (FBS) concentrations were exposed to low-level infrared laser (808 nm, 100 mW) at different fluences (10, 35, and 70 J/cm(2)) and evaluated after 24, 48, and 72 h. Cell viability was evaluated by WST-1 assay; reactive oxygen species (ROS), apoptosis, and necrosis were evaluated by flow cytometry. Cell viability was decreased atthe lowest FBS concentration. Laser exposure increased the cell viability in myoblast cultures at 2 % FBS after 48 and 72 h, but no significant increase in ROS was observed. Apoptosis was decreased at the higher fluence and necrosis was increased at lower fluence in myoblast cultures after 24 h of laser exposure at 2 % FBS. No laser-induced alterations were obtained at 10 % FBS. Results show that level of reactive oxygen species is not altered, at least to those evaluated in this study, but low-level infrared laser exposure affects cell viability, apoptosis, and necrosis in myoblast cultures depending on laser fluence and physiologic conditions of cells. PMID- 26886591 TI - Ameloblastomas of the mandible and maxilla. AB - PURPOSE OF REVIEW: This review focuses on issues in managing ameloblastomas of the mandible and maxilla. We will refer to current practice in the treatment of ameloblastomas based on the available evidence. RECENT FINDINGS: Recent reviews have been trying to establish natural history, growth patterns and malignant potential. This provides the clinicians and the patients with useful prognostic information. Controversies in management of ameloblastomas in relation to the type, age and site exist. This paper aims to categorize these issues. More recently, the authors have adopted the staged treatment approach as an additional step to ensure margin clearance. SUMMARY: Current evidence favours radical resection to provide better control rates. This applies to maxillary lesions of all ages, and solid mandibular lesions in adults (>18 years) where growth has ceased and the patient has matured enough to withstand the impact of resection and reconstruction. Conservative management is advocated for unicystic lesions with good control rates. In children and adolescents, a conservative approach is recommended. This approach aids to minimize both psychological and the impact on growth. Furthermore, most of the lesions are unicystic and the recurrent lesions have been shown to be much smaller and can be managed promptly within a good healthcare system. PMID- 26886590 TI - Distribution and Genetic Profiles of Campylobacter in Commercial Broiler Production from Breeder to Slaughter in Thailand. AB - Poultry and poultry products are commonly considered as the major vehicle of Campylobacter infection in humans worldwide. To reduce the number of human cases, the epidemiology of Campylobacter in poultry must be better understood. Therefore, the objective of the present study was to determine the distribution and genetic relatedness of Campylobacter in the Thai chicken production industry. During June to October 2012, entire broiler production processes (i.e., breeder flock, hatchery, broiler farm and slaughterhouse) of five broiler production chains were investigated chronologically. Representative isolates of C. jejuni from each production stage were characterized by flaA SVR sequencing and multilocus sequence typing (MLST). Amongst 311 selected isolates, 29 flaA SVR alleles and 17 sequence types (STs) were identified. The common clonal complexes (CCs) found in this study were CC-45, CC-353, CC-354 and CC-574. C. jejuni isolated from breeders were distantly related to those isolated from broilers and chicken carcasses, while C. jejuni isolates from the slaughterhouse environment and meat products were similar to those isolated from broiler flocks. Genotypic identification of C. jejuni in slaughterhouses indicated that broilers were the main source of Campylobacter contamination of chicken meat during processing. To effectively reduce Campylobacter in poultry meat products, control and prevention strategies should be aimed at both farm and slaughterhouse levels. PMID- 26886593 TI - A Woman With Right Hand and Leg Discoordination. PMID- 26886592 TI - Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis. AB - The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs. PMID- 26886594 TI - Severe Bloodstream Infection due to KPC-Producer E coli in a Renal Transplant Recipient Treated With the Double-Carbapenem Regimen and Analysis of In Vitro Synergy Testing: A Case Report. AB - Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited therapeutic options, innovative antimicrobial combinations against carbapenem-resistant Enterobacteriaceae causing severe infections are necessary.A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was complicated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Klebisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of meropenem plus ertapenem) and a potent synergistic and bactericidal activity of this un conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock.The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients. PMID- 26886595 TI - Long-Term Exposure to Ozone and Life Expectancy in the United States, 2002 to 2008. AB - Long-term exposure to ground-level ozone is associated with increased risk of morbidity and mortality. The association remains uncertain between long-term exposure to ozone and life expectancy. We assessed the associations between seasonal mean daily 8-hour maximum (8-hr max) ozone concentrations measured during the ozone monitoring seasons and life expectancy at birth in 3109 counties of the conterminous U.S. during 2002 to 2008. We used latent class growth analysis to identify latent classes of counties that had distinct mean levels and rates of change in ozone concentrations over the 7-year period and used linear regression analysis to determine differences in life expectancy by ozone levels. We identified 3 classes of counties with distinct seasonal mean daily 8-hr max ozone concentrations and rates of change. When compared with the counties with the lowest ozone concentrations, the counties with the highest ozone concentrations had 1.7- and 1.4-year lower mean life expectancy in males and females (both P < 0.0001), respectively. The associations remained statistically significant after controlling for potential confounding effects of seasonal mean PM2.5 concentrations and other selected environmental, demographic, socio economic, and health-related factors (both P < 0.0001). A 5 ppb higher ozone concentration was associated with 0.25 year lower life expectancy in males (95% CI: -0.30 to -0.19) and 0.21 year in females (95% CI: -0.25 to -0.17). We identified 3 classes of counties with distinct mean levels and rates of change in ozone concentrations. Our findings suggest that long-term exposure to a higher ozone concentration may be associated with a lower life expectancy. PMID- 26886597 TI - Atorvastatin Use Associated With Acute Pancreatitis: A Case-Control Study in Taiwan. AB - Few data are present in the literature on the relationship between atorvastatin use and acute pancreatitis. The aim of this study was to explore this issue in Taiwan. Using representative claims data established from the Taiwan National Health Insurance Program, this case-control study consisted of 5810 cases aged 20 to 84 years with a first-time diagnosis of acute pancreatitis during the period 1998 to 2011and 5733 randomly selected controls without acute pancreatitis. Both cases and controls were matched by sex, age, comorbidities, and index year of diagnosing acute pancreatitis. Subjects who at least received 1 prescription for other statins or nonstatin lipid-lowering drugs were excluded from the study. If subjects never had 1 prescription for atorvastatin, they were defined as never use of atorvastatin. Current use of atorvastatin was defined as subjects whose last remaining 1 tablet of atorvastatin was noted <=7 days before the date of diagnosing acute pancreatitis. Late use of atorvastatin was defined as subjects whose last remaining 1 tablet of atorvastatin was noted >7 days before the date of diagnosing acute pancreatitis. The odds ratio with 95% confidence interval of acute pancreatitis associated with atorvastatin use was calculated by using the logistic regression analysis. The logistic regression analysis revealed that the odds ratio of acute pancreatitis was 1.67 for subjects with current use of atorvastatin (95% confidence interval 1.18, 2.38), when compared with subjects with never use of atorvastatin. The odds ratio decreased to 1.15 for those with late use of atorvastatin (95% confidence interval 0.87, 1.52), but without statistical significance. Current use of atorvastatin is associated with the diagnosis of acute pancreatitis. Clinically, clinicians should consider the possibility of atorvastatin-associated acute pancreatitis when patients present with a diagnosis of acute pancreatitis without a definite etiology but are taking atorvastatin. PMID- 26886596 TI - Fbxw7 Tumor Suppressor: A Vital Regulator Contributes to Human Tumorigenesis. AB - Rapidly accumulating data indicate that F-box/WD repeat-containing protein 7 (Fbxw7) is one of the most frequently mutated genes in human cancers and regulates a network of crucial oncoproteins. These studies have generated important new insights into tumorigenesis and may soon enable therapies targeting the Fbxw7 pathway. We searched PubMed, Embase, and ISI Web of Science databases (1973-2015, especially recent 5 years) for articles published in the English language using the key words "Fbxw7," "Fbw7," "hCDC4," and "Sel-10," and we reviewed recent developments in the search for Fbxw7. Fbxw7 coordinates the ubiquitin-dependent proteolysis of several critical cellular regulators, thereby controlling essential processes, such as cell cycle, differentiation, and apoptosis. Fbxw7 contains 3 isoforms (Fbxw7alpha, Fbxw7beta, and Fbxw7gamma), and they are differently regulated in subtract recognition. Besides those, Fbxw7 activity is controlled at different levels, resulting in specific and tunable regulation of the abundance and activity of its substrates in a variety of human solid tumor types, including glioma malignancy, nasopharyngeal carcinoma, osteosarcoma, melanoma as well as colorectal, lung, breast, gastric, liver, pancreatic, renal, prostate, endometrial, and esophageal cancers. Fbxw7 is strongly associated with tumorigenesis, and the mechanisms and consequences of Fbxw7 deregulation in cancers may soon enable the development of novel therapeutic approaches. PMID- 26886598 TI - Absence of Bladder Outlet Obstruction Is an Independent Risk Factor for Prostate Cancer in Men Undergoing Prostate Biopsy. AB - The purpose of this study was to investigate the relationship between bladder outlet obstruction (BOO) and the risk of being diagnosed with prostate cancer (PCa).Study population consisted of 2673 patients scheduled for the first prostate biopsy (PBx). All patients underwent uroflowmetry before PBx; those with a peak flow rate (PFR) <10 mL/s were considered to have BOO.The incidence of PCa was 41.3% (1104/2673) in the overall population and 34.1% (659/1905) in patients with serum prostate-specific antigen (PSA) <= 10 ng/mL. Univariate and multivariate logistic regression analyses showed that patients with BOO had a significantly (P < 0.0001) lower risk than those without BOO of being diagnosed with PCa (33.1% vs 66.9% in the overall population; 30% vs 70% in patients with PSA <= 10 ng/mL). As the presence of BOO was significantly correlated to a large prostate volume, another independent predictor of PBx outcome, we tested whether these parameters could be used to identify, in the subset of patients with PSA<=10 ng/mL, those who could potentially be spared from a PBx. If we would have not biopsied patients with BOO and prostate volume >=60 mL, 14.5% of biopsies could have been avoided while missing only 6% of tumors. Only 10% of the tumors that would have been missed were high-risk cancers.In conclusion, in men undergoing PBx, the absence of BOO, as determined by a PFR >=10 mL/s, is an independent risk factor for PCa. Our study provides ground for this simple, noninvasive, objective parameter being used, alone or in combination with prostate volume, in the decision-making process of men potentially facing a PBx. PMID- 26886600 TI - Bedside Lung Ultrasound During Acute Chest Syndrome in Sickle Cell Disease. AB - Lung ultrasound (LU) is increasingly used to assess pleural and lung disease in intensive care unit (ICU) and emergency unit at the bedside. We assessed the performance of bedside chest radiograph (CR) and LU during severe acute chest syndrome (ACS), using computed tomography (CT) as the reference standard. We prospectively explored 44 ACS episodes (in 41 patients) admitted to the medical ICU. Three imaging findings were evaluated (consolidation, ground-glass opacities, and pleural effusion). A score was used to quantify and compare loss of lung aeration with each technique and assess its association with outcome. A total number of 496, 507, and 519 lung regions could be assessed by CT scan, bedside CR, and bedside LU, respectively. Consolidations were the most common pattern and prevailed in lung bases (especially postero-inferior regions). The agreement with CT scan patterns was significantly higher for LU as compared to CR (kappa coefficients of 0.45 +/- 0.03 vs 0.30 +/- 0.03, P < 0.01 for the parenchyma, and 0.73 +/- 0.08 vs 0.06 +/- 0.09, P < 0.001 for pleural effusion). The Bland and Altman analysis showed a nonfixed bias of -1.0 (P = 0.12) between LU score and CT score whereas CR score underestimated CT score with a fixed bias of -5.8 (P < 0.001). The specificity for the detection of consolidated regions or pleural effusion (using CT scan as the reference standard) was high for LU and CR, whereas the sensitivity was high for LU but low for CR. As compared to others, ACS patients with an LU score above the median value of 11 had a larger volume of transfused and exsanguinated blood, greater oxygen requirements, more need for mechanical ventilation, and a longer ICU length of stay. LU outperformed CR for the diagnosis of consolidations and pleural effusion during ACS. Higher values of LU score identified patients at risk of worse outcome. PMID- 26886599 TI - Prevalence of Undiagnosed Diabetes in Rheumatoid Arthritis: an OGTT Study. AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by an excess of cardiovascular disease (CVD) risk, estimated to be at least 50% greater when compared to the general population. Although the widespread diffusion of type 2 diabetes mellitus (T2DM) awareness, there is still a significant proportion of patients with T2DM that remain undiagnosed. Aim of this cross sectional study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in RA patients. For the present study, 100 consecutive nondiabetic RA patients were recruited. Age- and sex-matched subjects with noninflammatory diseases (osteoarthritis or fibromyalgia) were used as controls. After overnight fasting, blood samples were obtained for laboratory evaluation including serum glucose, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP), rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (ACPA). A standard Oral Glucose Tolerance Test (OGTT) with 75 g of glucose was performed and blood samples were collected at time 0, 30, 60, 90, and 120 minutes, for measurement of plasma glucose concentrations. The prevalence of impaired fasting glucose (IFG) (9/100 vs 12/100, P = 0.49), impaired glucose tolerance (IGT) (19/100 vs 12/100, P = 0.17), and concomitant IFG/IGT (5/100 vs 9/100, P = 0.27) was similar between groups, whereas the prevalence of diabetes was significantly higher in RA patients (10/100 vs 2/100, P = 0.02). In a logistic regression analysis, increasing age (OR = 1.13, 95% CI 1.028-1.245, P = 0.01) and disease duration (OR = 1.90, 95% CI 1.210-2.995, P = 0.005) were both associated with an increased likelihood of being classified as prediabetes (i.e. IFG and/or IGT) or T2DM. A ROC curve was built to evaluate the predictivity of disease duration on the likelihood of being diagnosed with T2DM. The area under the ROC curve was 0.67 (95% CI: 0.56-0.78, P = 0.004). We identified the best cut-off of 33 months that yielded a sensitivity of 61% and a specificity of 70% for classification of T2DM patients. According to our data, RA seems to be characterized by an elevated prevalence of undiagnosed diabetes, especially in patients with longer disease duration. PMID- 26886601 TI - Dipeptidyl Peptidase-4 Inhibitor Use Is Not Associated With Acute Pancreatitis in High-Risk Type 2 Diabetic Patients: A Nationwide Cohort Study. AB - To analyze the association between use of DPP-4 inhibitors and acute pancreatitis in high-risk type 2 diabetic patients. A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance claim database. The risk associated with sitagliptin was compared to that with acarbose, a second-line antidiabetic drug prescribed for patients with similar diabetes severity and with a known neutral effect on pancreatitis. Between January 1, 2009 and December 31, 2010, a total of 8526 sitagliptin initiators and 8055 acarbose initiators who had hypertriglyceridemia or prior hospitalization history for acute pancreatitis were analyzed for the risk of hospitalization due to acute pancreatitis stratified for baseline propensity score. In the crude analysis, sitagliptin was associated with a decreased risk of acute pancreatitis (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.62-0.88) compared to acarbose in diabetic patients with prior history of hospitalization for pancreatitis or hypertriglyceridemia. The association was abolished after stratification for propensity score quintiles (adjusted HR 0.95; 95% CI: 0.79-1.16). Similar results were found separately in both patients' histories of prior hospitalization of acute pancreatitis (adjusted HR 0.97; 95% CI: 0.76-1.24) and those with hypertriglyceridemia (adjusted HR 0.86; 95% CI: 0.65-1.13). No significant association was found for different durations or accumulative doses of sitagliptin. In the stratified analysis, no significant effect modification was found in relation to patients' characteristics. Use of sitagliptin was not associated with an increased risk of acute pancreatitis in high-risk diabetic patients with hypertriglyceridemia or with history of acute pancreatitis. PMID- 26886602 TI - Comparison of Standard Automated Perimetry, Short-Wavelength Automated Perimetry, and Frequency-Doubling Technology Perimetry to Monitor Glaucoma Progression. AB - Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression.Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models.No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP.SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes. PMID- 26886603 TI - The Prevalence of Mental Disorders Among Children and Adolescents in the Child Welfare System: A Systematic Review and Meta-Analysis. AB - It remains unclear whether children and adolescents in the child welfare system (CWS) exhibit a higher prevalence of mental disorders compared with the general population. The objective of this study was to perform a systematic review and meta-analysis to assess the prevalence of mental disorders in the CWS.A ll of the epidemiological surveys assessing the prevalence of mental disorders in children and adolescents in the CWS were included. The pooled prevalence was estimated with random effect models. Potential sources of heterogeneity were explored using meta-regression analyses.E ight studies provided prevalence estimates that were obtained from 3104 children and adolescents. Nearly 1 child or adolescent of every 2 (49%; 95% confidence interval (CI) 43-54) was identified as meeting criteria for a current mental disorder. The most common mental disorder was disruptive disorder (27%; 95% CI 20-34), including conduct disorder (20%; 95% CI 13-27) and oppositional defiant disorder (12%; 95% CI 10-14). The prevalence of attention-deficit/hyperactivity disorder was estimated to be 11% (95% CI 6-15). The prevalence estimates of anxiety and depressive disorders were 18% (95% CI 12 24) and 11% (95% CI 7-15). Posttraumatic stress disorder had the lowest prevalence (4%; 95% CI 2-6). High prevalences of mental disorders in the CWS were reported, which highlights the need for the provision of qualified service. The substantial heterogeneity of our findings is indicative of the need for accurate epidemiological data to effectively guide public policy. PMID- 26886604 TI - Growing Teratoma Syndrome Secondary to Ovarian Giant Immature Teratoma in an Adolescent Girl: A Case Report and Literature Review. AB - Growing teratoma syndrome (GTS) is a rare clinical entity first described by Logothetis et al in 1982. Although it is unusual for GTS to be located in the ovary, this report is of a case of an adolescent girl who underwent a complete surgical resection of the mass. Histopathology confirmed only an immature teratoma had originated from the ovary and so she received adjuvant chemotherapy with blemycin, etopside, and cisplatin over 4 cycles. Results from an abdominal enhanced CT (computed tomography) 9 years later revealed a giant mass had compressed adjacent tissues and organs. Laparotomy was performed and a postoperative histopathology showed the presence of a mature teratoma, and so the diagnosis of ovarian GTS was made. One hundred one cases of ovarian GTS from English literature published between 1977 and 2015 were collected and respectively analyzed in large samples for the first time. The median age of diagnosis with primary immature teratoma was 22 years (range 4-48 years, n = 56). GTS originating from the right ovary accounted for 57% (27/47, n = 47) whereas the left contained 43% (20/47, n = 47). Median primary tumor size was 18.7 cm (range 6-45 cm, n = 28) and median subsequent tumor size was 8.6 cm (range 1-25 cm, n = 25). From the primary treatment to the diagnosis of ovarian GTS, median tumor growth speed was 0.94 cm/month (range 0.3-4.3 cm/month, n = 21). Median time interval was 26.6 months (range 1-264 months, n = 41). According to these findings, 5 patients did have a pregnancy during the time interval between primary disease and GTS, making our patient the first case of having a pregnancy following the diagnosis of ovarian GTS. Because of its high recurrence and insensitiveness to chemotherapy, complete surgical resection is the preferred treatment and fertility-sparing surgery should be considered for women of child bearing age. Anyhow GTS of the ovary has an excellent prognosis. Patients with GTS had no evidence of recurrence or were found to be disease free during a 40.3 month (range 1-216 months, n = 48) median follow-up. Moreover, regular follow-ups with imaging and serum tumor markers are important and must not be neglected. PMID- 26886605 TI - Lessons Learned From a Case of Gastric Cancer After Liver Transplantation for Hepatocellular Carcinoma: A Case Report and Literatures Review. AB - Nowadays, de novo malignancies have become an important cause of death after transplantation. According to the accumulation of cases with liver transplantation, the incidence of de novo gastric cancer is anticipated to increase among liver transplant recipients in the near future, especially in some East Asian countries where both liver diseases requiring liver transplantation and gastric cancer are major burdens. Unfortunately, there is limited information regarding the relationship between de novo gastric cancer and liver transplantation. Herein, we report a case of stage IIIc gastric cancer after liver transplantation for hepatocellular carcinoma, who was successfully treated by radical distal gastrectomy with D2 lymphadenectomy but died 15 months later due to tumor progression. Furthermore, we extract some lessons to learn from the case and review the literatures. The incidence of de novo gastric cancer following liver transplantations is increasing and higher than the general population. Doctors should be vigilant in early detection and control the risk factors causing de novo gastric cancer after liver transplantation. Curative gastrectomy with D2 lymphadenectomy is still the mainstay of treatment for such patients. Preoperative assessments, strict postoperative monitoring, and managements are mandatory. Limited chemotherapy could be given to the patients with high risk of recurrence. Close surveillance, early detection, and treatment of posttransplant cancers are extremely important and essential to improve the survival. PMID- 26886606 TI - The Power of Renal Function Estimation Equations for Predicting Long-Term Kidney Graft Survival: A Retrospective Comparison of the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease Study Equations. AB - Evaluation of renal function using an accurate estimation equation is important for predicting long-term graft survival. We designed this retrospective cohort study to evaluate the predictive power of renal function estimation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) study equations for graft survival. We reviewed data of 3290 adult kidney transplant recipients who underwent transplantation at a single center between April 1979 and September 2012. The reliability and agreement of chronic kidney disease (CKD) stages based on the estimated glomerular filtration rate (eGFR) as calculated by the CKD-EPI and MDRD equations were evaluated using Bland-Altman plots and Cohen weighted kappa analyses. The predictive power of CKD stages as classified by each equation for graft survival was investigated using Cox regression models. Additionally, Pearson and Spearman correlation coefficients were used to reveal the relationship between graft survival and eGFR equations. Of 3290 kidney transplant recipients, 3040 were included in the analysis. The mean follow-up duration was 128.08 +/- 83.54 months, and 29.8% of participants were reclassified to higher eGFR categories by the CKD-EPI equation compared to the category classification by the MDRD equation. eGFR calculated using the MDRD equation was underestimated compared to that calculated using the CKD-EPI equation, based on the Bland-Altman plot. In Cohen weighted kappa analysis, agreement across CKD stages classified using the 2 equations was reliable, but all CKD stages classified using the MDRD equation appeared to be in lower eGFR categories than those classified using the CKD-EPI equation. Pearson and Spearman correlation analyses indicated that the CKD stage as classified by the CKD-EPI equation, but not the MDRD equation, was significantly correlated with the risk of graft failure. In multivariable Cox regression analysis for graft failure after adjustment for CKD stage as determined using the MDRD equation, but not the CKD-EPI equation, stage reclassification was significantly associated with a lower graft failure risk. Our data from this long-term follow-up study indicate that the CKD-EPI equation has a stronger predictive power for kidney graft survival than does the MDRD equation in transplantation settings. PMID- 26886607 TI - Prognosis Predicting Score for Endovascular Treatment of Aneurysmal Subarachnoid Hemorrhage: A Risk Modeling Study for Individual Elderly Patients. AB - The elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) have a greater risk of poor clinical outcome after endovascular treatment (EVT) than younger patients do. Hence, it is necessary to explore which factors are associated with poor outcome and develop a predictive score specifically for elderly patients with aSAH receiving EVT. The aim of this study was to develop and validate a predictive score for 1-year outcomes in individual elderly patients with aSAH underwent EVT.In this 10-year prospective study, 520 consecutive aSAH elderly (age >= 60 years) patients underwent EVT in a single center were included. The risk factors, periprocedural, and 1-year follow-up data of all patients were entered in a specific prospective database. The modified Rankin scale was used for evaluating clinical outcome. To optimize the model's predictive capacity, the original matrix was randomly divided in 2 submatrices (learning and testing). The predictive score was developed using Arabic numerals for all variables based on the variable coefficients (beta) of multivariable logistic regression analysis in the learning set and the predictive performance evaluation was assessed in the testing set. The risk classes were constructed using classification criteria based on sensitivity and specificity. The poor outcome rate at 1 year was 26.15%. Six risk factors, including age, hypertension, Hunt-Hess scale, Fisher scale, aneurysm location, and periprocedural complications, were independently associated with poor outcome and assembled the Changhai score. The discriminative power analysis with the area under the receiver operating characteristic curve (AUC) of the Changhai score was statistically significant (0.864, 0.824-0.904, P < 0.001). The sensitivity and specificity of the Changhai score were 82.07% and 78.06%, respectively. Our study indicated that age, hypertension, Hunt-Hess scale, Fisher scale, aneurysm location, and periprocedural complications were independent risk factors of poor outcome for elderly aSAH patients underwent EVT. In combination with these risk factors, the Changhai score can be a useful tool in the prediction of clinical outcome but needs to be validated in various centers before it can be recommended for application. PMID- 26886609 TI - Change of Nutritional Status Assessed Using Subjective Global Assessment Is Associated With All-Cause Mortality in Incident Dialysis Patients. AB - Subjective global assessment (SGA) is associated with mortality in end-stage renal disease (ESRD) patients. However, little is known whether improvement or deterioration of nutritional status after dialysis initiation influences the clinical outcome. We aimed to elucidate the association between changes in nutritional status determined by SGA during the first year of dialysis and all cause mortality in incident ESRD patients. This was a multicenter, prospective cohort study. Incident dialysis patients with available SGA data at both baseline and 12 months after dialysis commencement (n = 914) were analyzed. Nutritional status was defined as well nourished (WN, SGA A) or malnourished (MN, SGA B or C). The patients were divided into 4 groups according to the change in nutritional status between baseline and 12 months after dialysis commencement: group 1, WN to WN; group 2, MN to WN; group 3, WN to MN; and group 4, MN to MN. Cox proportional hazard analysis was performed to clarify the association between changes in nutritional status and mortality. Being in the MN group at 12 months after dialysis initiation, but not at baseline, was a significant risk factor for mortality. There was a significant difference in the 3-year survival rates among the groups (group 1, 92.2%; group 2, 86.0%; group 3, 78.2%; and group 4, 63.5%; log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the mortality risk was significantly higher in group 3 than in group 1 (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.27-6.03, P = 0.01) whereas the mortality risk was significantly lower in group 2 compared with group 4 (HR 0.35, 95% CI 0.17-0.71, P < 0.01) even after adjustment for confounding factors. Moreover, mortality risk of group 3 was significantly higher than in group 2 (HR 2.89, 95% CI 1.22-6.81, P = 0.02); there was no significant difference between groups 1 and 2. The changes in nutritional status assessed by SGA during the first year of dialysis were associated with all-cause mortality in incident ESRD patients. PMID- 26886608 TI - Targeted Disruption of miR-17-92 Impairs Mouse Spermatogenesis by Activating mTOR Signaling Pathway. AB - The miR-17-92 cluster and its 6 different mature microRNAs, including miR-17, miR 18a, miR-19a, miR-20a, miR-19b-1, and miR-92a, play important roles in embryo development, immune system, kidney and heart development, adipose differentiation, aging, and tumorigenicity. Currently, increasing evidence indicates that some members of miR-17-92 cluster may be critical players in spermatogenesis, including miR-17, miR-18a, and miR-20a. However, the roles and underlying mechanisms of miR-17-92 in spermatogenesis remain largely unknown. Our results showed that the targeted disruption of miR-17-92 in the testes of adult mice resulted in severe testicular atrophy, empty seminiferous tubules, and depressed sperm production. This phenotype is partly because of the reduced number of spermatogonia and spermatogonial stem cells, and the significantly increased germ cell apoptosis in the testes of miR-17-92-deficient mice. In addition, overactivation of the mammalian target of rapamycin signaling pathway and upregulation of the pro-apoptotic protein Bim, Stat3, c-Kit, and Socs3 were also observed in miR-17-92-deficient mouse testes, which might be, at least partially if not all, responsible for the aforementioned phenotypic changes in mutant testes. Taken together, these findings suggest that miR-17-92 is essential for normal spermatogenesis in mice. PMID- 26886610 TI - How Strong Is the Evidence for Sodium Bicarbonate to Prevent Contrast-Induced Acute Kidney Injury After Coronary Angiography and Percutaneous Coronary Intervention? AB - Hydration with sodium bicarbonate is one of the strategies to prevent contrast induced acute kidney injury (CI-AKI). The purpose of this study was to determine how strong is the evidence for sodium bicarbonate to prevent CI-AKI after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI).We conducted PubMed, EMBASE, and CENTRAL databases to search for randomized controlled trials (RCTs) comparing the efficacy of sodium bicarbonate with sodium chloride to prevent CI-AKI after CAG and/or PCI. Relative risk (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated. Heterogeneity, publication bias, and study quality were evaluated, sensitivity analyses, cumulative analyses, and subgroup analyses were performed. The risk of random errors was assessed by trial sequential analysis (TSA).Sixteen RCTs (3537 patients) met the eligibility criteria. Hydration with sodium bicarbonate showed significant beneficial effects in preventing CI-AKI (RR 0.67; 95% CI: 0.47-0.96, P = 0.029), decreasing the change in serum creatinine (SCr) (SMD -0.31 95% CI: -0.55 to -0.07, P = 0.011) and estimated glomerular filtration rate (eGFR) (SMD -0.17 95% CI: -0.30 to 0.04, P = 0.013). But no significant differences were observed in the requirement for dialysis (RR 1.11; 95% CI: 0.60-2.07, P = 0.729), mortality (RR 0.71; 95% CI: 0.41-1.21, P = 0.204) and reducing the length of hospital stay (LHS) (WMD -1.47; 95% CI: -4.14 to 1.20, P = 0.279). The result of TSA on incidence of CI-AKI showed the required information size (RIS = 6614) was not reached and cumulative z curve did not cross TSA boundary. The result of TSA on the requirement for dialysis and mortality demonstrated the required information sizes (RIS = 170,510 and 19,516, respectively) were not reached, and the cumulative z-curve did not cross any boundaries.The evidence that sodium bicarbonate reduces the incidence of CI-AKI is encouraging but more well-designed randomized controlled trails are required to allow definitive firm conclusion to be drawn. PMID- 26886611 TI - Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients. AB - Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 +/- 0.50. During a follow-up period of 35.4 +/- 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients. PMID- 26886612 TI - Predicting Hepatic Steatosis in Living Liver Donors via Noninvasive Methods. AB - Hepatic steatosis assessment is of paramount importance for living liver donor selection because significant hepatic steatosis can affect the postoperative outcome of recipients and the safety of the donor. The validity of various noninvasive imaging methods to assess hepatic steatosis remains controversial. The purpose of our study is to investigate the association between noninvasive imaging methods and pathology to detect steatosis in living liver donors and to propose a prediction model for hepatic steatosis. Liver stiffness measurements (LSMs) and controlled attenuation parameter values in vibration controlled transient elastography, ultrasonography, computed tomography (CT), and magnetic resonance imaging were used as pretransplant screening methods to evaluate living liver donors between 2012 and 2014. Only 1 pathologist assessed tissue sample for hepatic steatosis. The median age of the 79 living donors (53 men and 26 women) was 32 years (16-68 years). The CT liver-spleen attenuation (L-S) difference and the controlled attenuation parameter values were well correlated with the level of hepatic steatosis on liver pathology. Multivariate analysis showed that liver stiffness measurement (LSM) (beta = 0.903; 95% CI, 0.105-1.702; P = 0.027) and the CT L to S attenuation difference (beta = -3.322; 95% CI, -0.502 to -0.142; P = 0.001) were closely associated with hepatic steatosis. We generated the following equation to predict total hepatic steatosis: Hepatic steatosis = 0.903 * LSM - 0.322 * CT L to S attenuation difference (AUC = 86.6% and P = 0.001). The values predicted by the equation correlated well with the presence of hepatic steatosis (r = 0.509 and P < 0.001). The combination of nonenhanced CT L to S attenuation difference and transient elastography using vibration controlled transient elastography provides sufficient information to predict hepatic steatosis in living liver donor candidates. PMID- 26886613 TI - The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer. AB - Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score. PMID- 26886614 TI - Multiple Ewing Sarcoma/Primitive Neuroectodermal Tumors in the Mediastinum: A Case Report and Literature Review. AB - Ewing sarcoma/primitive neuroectodermal tumors (ES/PNET) are high-grade malignant neoplasms. These malignancies present very rare tumors of thoracopulmonary area and even rarer in the mediastinum. In our knowledge, ES/PNET presented with multiple mediastinal masses has not been reported previously. We experienced a case of a 42-year-old man presented with gradual onset of left-side pleuritic chest pain. A contrast-enhanced chest computed tomography (CT) scan showed separate 2 large heterogeneously enhancing masses in each anterior and middle mediastinum of the left hemithorax. Positron emission tomography-computed tomography (PET-CT) scan revealed high fluorodeoxyglucose (FDG) uptake in the mediastinal masses. After surgical excision for the mediastinal masses, both of the masses were diagnosed as the ES/PNET group of tumors on the histopathologic examination. The patient refused postoperative adjuvant chemotherapy and came back with local tumor recurrence and distant metastasis on 4-month follow-up after surgical resection. We report this uncommon form of ES/PNET. We are to raise awareness that this rare malignancy should be considered as a differential diagnosis of the malignant mediastinal tumors and which can be manifested as multiple masses in a patient. Understanding this rare entity of extra-skeletal ES/PNET and characteristic imaging findings can help radiologists and clinicians to approach proper diagnosis and better management for this highly malignant tumor. PMID- 26886615 TI - Clinical and Radiological Characteristics of Lumbosacral Lateral Disc Herniation in Comparison With Those of Medial Disc Herniation. AB - Lateral disc herniation (foraminal and extra foraminal) has clinical characteristics that are different from those of medial disc herniation (central and subarticular), including older age, more frequent radicular pain, and neurologic deficits. This is supposedly because lateral disc herniation mechanically irritates or compresses the exiting nerve root or dorsal root ganglion inside of a narrow canal more directly than medial disc herniation. The purpose of this study was to investigate clinical and radiological characteristics of lateral disc herniation in comparison with medial disc herniation. The 352 subjects diagnosed with localized lumbosacral disc herniation and followed up for at least 12 months after completion of treatment were included and divided into medial and lateral disc herniation groups, according to the anatomical location of the herniated disc in axial plain of magnetic resonance image. Clinical and radiological data were obtained and compared between the two groups. The lateral group included 74 (21%) patients and the medial group included 278 (79%). Mean age of the lateral group was significantly higher than that in the medial group. The lateral group showed a significantly larger proportion of patients with radiating leg pain and multiple levels of disc herniations than the medial group. No significant differences were found in terms of gender, duration of pain, pretreatment numeric rating scale, severity of disc herniation (protrusion and extrusion), and presence of weakness in leg muscles. The proportion of patients who underwent surgery was not significantly different between the 2 groups. However, the proportion of patients who accomplished successful pain reduction after treatment was significantly smaller in the lateral than in the medial group. In conclusion, patients with lateral disc herniation were older and had larger proportion of radiating leg pain than those with medial disc herniation. Lateral disc herniation was more associated with multiple disc herniations and worse clinical outcomes after treatment than medial disc herniation. PMID- 26886617 TI - Tailored Therapy Versus Empiric Chosen Treatment for Helicobacter pylori Eradication: A Meta-Analysis. AB - Although various regimens are empirically accepted for Helicobacter pylori eradication, the efficacy might be declined by multiple individual factors. The necessity of a personalized eradication therapy still remains controversial. The aim of the study was to compare tailored therapy with empiric chosen regimens. Databases of PUBMED, EMBASE, and MEDLINE were searched for eligible studies, published up to October 2015. All relevant controlled clinical trials were included. A random-effect model was applied to compare pooled relative risk (RR) with related 95% confidence intervals (CIs).Thirteen controlled clinical trials integrating 3512 participants were assessed. Overall, the pooled eradication rates of tailored groups were higher than those of empiric ones (intention-to treat: RR = 1.16, 95% CI 1.10-1.22; preprotocol: RR = 1.14, 95% CI 1.08-1.21). In subgroup analysis, tailored therapy was superior to 7-day standard triple therapy (RR = 1.22, 95% CI 1.16-1.29) and bismuth-quadruple therapy (RR = 1.14, 95% CI 1.07-1.22) on eradication rates; first-line tailored therapy achieved higher eradication rates than first-line empirical regimens (pooled RR = 1.18, 95%CI 1.14-1.22), whereas tailored rescue regimen showed no difference with empirical ones (pooled RR = 1.16, 95% CI 0.96-1.39). Moreover, among different tailored designs, susceptibility-guided tailored therapy obtained higher eradication rates than empiric groups, independent of CYP2C19 genotype detection (with CYP: RR = 1.16, 95% CI 1.09-1.23; without CYP: RR = 1.14, 95% CI 1.01-1.28). Both molecular test-based and culture-based tailored groups were better on eradication rates than empiric groups (molecular: RR = 1.23, 95% CI 1.11-1.35; culture: RR = 1.13, 95% CI 1.06-1.20). Compared with empiric chosen treatments, tailored therapy is a better alternative for H pylori eradication. PMID- 26886616 TI - Metformin Is Associated With Slightly Reduced Risk of Colorectal Cancer and Moderate Survival Benefits in Diabetes Mellitus: A Meta-Analysis. AB - To systematically assess the effect of metformin on colorectal cancer (CRC) risk and mortality in type 2 diabetes mellitus (T2DM) patients. We conducted a systematic search of PubMed, Web of Science, and the Cochrane Library databases for relevant articles before August 2015. Two investigators identified and extracted data independently. We adopted adjusted estimates to calculate summary estimates with 95% confidence interval (CI) using either a fixed-effects or a random-effects model. Subgroup and sensitivity analyses were conducted to evaluate the robustness of the pooled results. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Begg test and Egger test. Fifteen studies on CRC incidence and 6 studies on CRC survival were finally included in our meta-analysis. The pooled odds ratio (OR) of observational studies illustrated that a slight 10% reduction of CRC incidence was associated with metformin use (OR = 0.90, 95% CI: 0.85-0.96). Furthermore, the pooled hazard ratio (HR) revealed an improved survival outcome for metformin users in CRC patients compared to nonusers (HR = 0.68, 95% CI: 0.58-081). There was no publication bias across studies. Our meta-analysis demonstrated that metformin therapy could slightly reduce CRC incidence and moderately improve the survival outcomes in patients with T2DM. More prospective studies are warranted to certify this protective association. PMID- 26886618 TI - Multimorbidity: Epidemiology and Risk Factors in the Golestan Cohort Study, Iran: A Cross-Sectional Analysis. AB - Advances in medicine and health policy have resulted in growing of older population, with a concurrent rise in multimorbidity, particularly in Iran, as a country transitioning to a western lifestyle, and in which the percent of the population over the age of 60 years is increasing. This study aims to assess multimorbidity and the associated risk factors in Iran. We used data from 50,045 participants (age 40-75 y) in the Golestan Cohort Study, including data on demographics, lifestyle habits, socioeconomic status, and anthropometric indices. Multimorbidity was defined as the presence of 2 or more out of 8 self-reported chronic conditions, including cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, liver disease, gastroesophageal reflux disease, tuberculosis, and cancer. Multivariate logistic regression models were used to examine the associations between multiple different factors and the risk factors. Multimorbidity prevalence was 19.4%, with the most common chronic diseases being gastroesophageal reflux disease (76.7%), cardiovascular diseases (72.7%), diabetes (25.3%), and chronic obstructive pulmonary disease (21.9%). The odds of multimorbidity was 2.56-fold higher at the age of >60 years compared with that at <50 years (P < 0.001), and 2.11-fold higher in women than in men (P < 0.001). Other factors associated with higher risk of multimorbidity included non-Turkmen ethnicity, low education, unemployment, low socioeconomic status, physical inactivity, overweight, obesity, former smoking, opium and alcohol use, and poor oral health. Apart from advanced age and female sex, the most important potentially modifiable lifestyle factors, including excess body weight and opium use, and opium user, are associated with multimorbidity. Policies aiming at controlling multimorbidity will require a multidimensional approach to reduce modifiable risk factors in the younger population in developing countries alongside adopting efficient strategies to improve life quality in the older population. PMID- 26886619 TI - Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure. AB - Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46-12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF. PMID- 26886620 TI - Differential Postoperative Effects of Volatile Anesthesia and Intraoperative Remifentanil Infusion in 7511 Thyroidectomy Patients: A Propensity Score Matching Analysis. AB - Although remifentanil is used widely by many clinicians during general anesthesia, there are recent evidences of opioid-induced hyperalgesia as an adverse effect. This study aimed to determine if intraoperative remifentanil infusion caused increased pain during the postoperative period in patients who underwent a thyroidectomy. A total of 7511 patients aged >= 20 years, who underwent thyroidectomy between January 2009 and December 2013 at the Asan Medical Center were retrospectively analyzed. Enrolled patients were divided into 2 groups: group N (no intraoperative remifentanil and only volatile maintenance anesthesia) and group R (intraoperative remifentanil infusion including total intravenous anesthesia and balanced anesthesia). Following propensity score matching analysis, 2582 patients were included in each group. Pain scores based on numeric rating scales (NRS) were compared between the 2 groups at the postoperative anesthetic care unit and at the ward until 3 days postoperation. Incidences of postoperative complications, such as nausea, itching, and shivering were also compared. The estimated NRS pain score on the day of surgery was 5.08 (95% confidence interval [CI] 4.97-5.19) in group N patients and 6.73 (95% CI 6.65-6.80) in group R patients (P < 0.001). There were no statistically significant differences in NRS scores on postoperative days 1, 2, and 3 between the 2 groups. Postoperative nausea was less frequent in group R (31.4%) than in group N (53.5%) (P < 0.001). However, the incidence of itching was higher in group R (4.3%) than in group N (0.7%) (P < 0.001). Continuous infusion of remifentanil during general anesthesia can cause higher intensity of postoperative pain and more frequent itching than general anesthesia without remifentanil infusion immediately after thyroidectomy. Considering the advantages and disadvantages of continuous remifentanil infusion, volatile anesthesia without opioid may be a good choice for minor surgeries, such as thyroidectomy. PMID- 26886621 TI - Creutzfeldt-Jakob Disease Presenting With Dizziness and Gaze-Evoked Nystagmus: A Case Report. AB - Sporadic Creutzfeldt-Jakob disease (CJD) is clinically characterized by rapidly progressive dementia combined with other cardinal symptoms, such as myoclonus, visual or cerebellar disturbances, extrapyramidal or pyramidal disturbance, and akinetic mutism. However, as an initial manifestation, focal neurologic deficits other than the aforementioned or nonspecific generalized symptoms may lead to a misdiagnosis or a delayed diagnosis. The authors report a case of 66-year-old male patient with sporadic CJD who had dizziness, gaze-evoked nystagmus (GEN), and other central eye signs (impaired smooth pursuit, saccadic dysmetria) as an initial manifestation without dementia. The central eye signs led us to perform brain magnetic resonance images, which showed abnormal cortical high-signal intensity in both the cerebral and cerebellar hemispheres including the vestibulocerebellum. We reached a presumptive diagnosis of CJD, but the findings did not meet diagnostic criteria for probable CJD at that time. Three weeks after the initial work-ups, the patient presented with typical neurological findings of CJD: rapidly progressive dementia, akinetic mutism, and myoclonus of the left arm. Cerebrospinal fluid was positive for 14-3-3 protein, and electroencephalography showed periodic sharp wave complexes. In this patient, GEN and other central eye signs provided diagnostic clues for CJD. These unusual neurological manifestations may help physicians have a thorough knowledge of early deficits of CJD. PMID- 26886622 TI - Comparison of Clinical Outcome Between Twice-Weekly and Thrice-Weekly Hemodialysis in Patients With Residual Kidney Function. AB - Residual kidney function (RKF) contributes to improved survival in hemodialysis (HD) patients. However, it is not clear whether RKF allows a comparable survival rate in patients undergoing twice-weekly HD compared with thrice-weekly HD.We enrolled 685 patients from a prospective multicenter observational cohort. RKF and HD adequacy was monitored regularly over 3-year follow-up. Patients with RKF were divided into groups undergoing twice-weekly HD (n = 113) or thrice-weekly HD (n = 137). Patients without RKF undergoing thrice-weekly HD (n = 435) were included as controls. Fluid balance and dialysis-associated characteristics were followed and clinical outcomes evaluated using all-cause mortality and cardiovascular events (CVE).In patients with RKF, baseline and follow-up RKF were significantly higher in patients undergoing twice-weekly HD than in those undergoing thrice-weekly HD. Total Kt/V urea (dialysis plus residual renal) in patients with RKF undergoing twice-weekly HD was greater than or equal to those in patients with or without RKF undergoing thrice-weekly HD. Compared with patients with RKF undergoing thrice-weekly HD, patients with RKF undergoing twice weekly HD had no fluid excess, but their normalized protein catabolic rate became lower since 24-month follow up. In multivariable analyses, patients with RKF undergoing twice-weekly HD had a noninferior risk of mortality (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.34-2.01, P = 0.68) and of CVE (HR, 0.60; 95% CI, 0.28-1.29, P = 0.19) compared with patients without RKF undergoing thrice-weekly HD. However, this group showed an independent association with a greater risk of mortality compared with patients with RKF undergoing thrice-weekly HD (HR, 4.20; 95% CI, 1.02-17.32, P = 0.04).In conclusion, patients with RKF undergoing twice-weekly HD had an increased risk of mortality compared with those undergoing thrice-weekly HD. Decisions about twice weekly HD should consider not only RKF, but also other risk factors such as normalized protein catabolic rate. PMID- 26886623 TI - Incidence, Surgical Treatment, and Prognosis of Anorectal Melanoma From 1973 to 2011: A Population-Based SEER Analysis. AB - Anorectal melanoma (AM) is a rare type of melanoma that accounts for 0.4% to 1.6% of total malignant melanomas. The incidence of AM increases over time, and it remains highly lethal, with a 5-year survival rate of 6% to 22%. Considering the rare nature of this disease, most studies on AM comprise isolated case reports and single-center trials, which could not provide comprehensive assessment of the disease. Therefore, we conducted a population-based study by using the Surveillance, Epidemiology, and End Results (SEER) program to provide the latest and best available evidence of AM.We extracted all cases of AM registered in the SEER database from 1973 to 2011 (April 2014 release) and calculated age-adjusted incidence. Only cases with active follow-up were included to predict factors associated with prognosis. Survival outcomes were also compared among different types of surgery.We identified 640 AM cases, which consisted of 265 rectal melanoma and 375 anal melanoma. The estimated annual incidence rates of AM per 1 million population were 0.259 in males and 0.407 in females, and it increased with advanced age and over time. Tumor stage and surgical treatment were independent predictors of survival. Results implied that surgery improved the prognosis of patients with local- and regional-stage AM but could not prolong the survival of patients with distant-stage AM. Moreover, the outcome of less extensive excision was not statistically different from that of more extensive excision.This study provides an up-to-date estimation of the incidence and prognosis of AM by using SEER data. The incidence of AM continuously increases over time, despite its rarity. This disease also exhibits poor prognosis. Thus, AM must be further investigated in future studies. We also recommend surgery as the optimal treatment for local- and regional-stage AM patients but not for those with distant metastasis. PMID- 26886624 TI - Genetic Polymorphisms in Long Noncoding RNA H19 Are Associated With Susceptibility to Breast Cancer in Chinese Population. AB - H19, a maternally expressed imprinted gene transcribing a long noncoding RNA, has previously been reported to be involved in tumorigenesis and cancer progression. However, the association between the H19 polymorphisms and breast cancer (BC) susceptibility has remained elusive. The aim of this study was to evaluate the associations between 2 H19 haplotype tagging SNPs (rs3741219 T>C, rs217727 C>T) and the risk of breast cancer. Our study comprised 464 BC patients and 467 cancer free controls in China. rs3741219 and rs217727 were genotyped with polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and created restriction site PCR (CRS-RFLP) assays, respectively. False-positive report probability (FPRP) was calculated to test the false-positive association. On performing univariate analysis, no significant association between H19 polymorphisms (rs3741219 and rs217727) and BC was observed. However, in further stratified analyses, CT+TT genotypes of rs217727 had a significantly lower risk of breast cancer among women with number of pregnancy >2 (OR = 0.79; 95% CI = 0.55-0.97). CT genotype of rs217727 was associated with ER positivity (OR = 2.19; 95 % CI = 1.07-4.45) and HER-2 positivity (OR = 1.34; 95 % CI = 1.05-2.12). It was proved that our results were less likely to be false positives according to false-positive report probability calculation. Our findings extend available data on the association of H19 polymorphisms and BC susceptibility. Further validation in large population or cohort studies is needed. PMID- 26886626 TI - Quick and Easy Screening for Vitamin D Insufficiency in Adults: A Scoring System to Be Implemented in Daily Clinical Practice. AB - Vitamin D is essential regarding several health outcomes. Prevention of insufficiency (25-hydroxyvitamin D concentration <=20 ng/mL) generally entails blood testing and/or supplementation, strategies that should target at-risk individuals because blood testing is costly, and unwarranted supplementation could result in vitamin D overload with unknown long-term consequences. Our objective was to develop a simple score (Vitamin D Insufficiency Prediction score, VDIP) for identifying adults at risk of vitamin D insufficiency. Subjects were 1557 non-vitamin D-supplemented middle-aged adults from the SU.VI.MAX cohort. Scoring points corresponded to the rounded odds ratio for each individual level characteristic associated with vitamin D insufficiency in a multivariable logistic regression model. Receiver operating characteristic curve (area under curve), sensitivity, specificity, and positive and negative predictive values were computed. External validation was performed in an independent cohort (NutriNet-Sante, N = 781). For female sex, overweight, low physical activity, winter season, moderate sun exposure, and very fair or dark skin 1.5 points were attributed; 2 points for latitude >=48 degrees N and spring season; 2.5 points for obesity and late winter; 3 points for low sun exposure. Points were then summed up for each participant. The VDIP score had an AUC = 0.70 +/- 0.01 (validation: 0.67 +/- 0.02). With a score of 7 or more, 70% of the participants were vitamin D-insufficient (80% in those with a score >=9), sensitivity/specificity were 0.67/0.63, and positive and negative predictive values were 0.70/0.59. The VDIP score performed well in identifying middle-aged adults at risk of vitamin D insufficiency (score >=7, moderate risk; score>=9, high risk), using only simple individual-level characteristics easily assessable in day-to-day clinical practice. Implementation of this simple and costless score could thus obviate unwarranted supplementation and/or blood testing. PMID- 26886625 TI - The Source and Credibility of Colorectal Cancer Information on Twitter. AB - Despite the rapid penetration of social media in modern life, there has been limited research conducted on whether social media serves as a credible source of health information. In this study, we propose to identify colorectal cancer information on Twitter and assess its informational credibility. We collected Twitter messages containing colorectal cancer-related keywords, over a 3-month period. A review of sample tweets yielded content and user categorization schemes. The results of the sample analysis were applied to classify all collected tweets and users, using a machine learning technique. The credibility of the information in the sampled tweets was evaluated. A total of 76,119 tweets were analyzed. Individual users authored the majority of tweets (n = 68,982, 90.6%). They mostly tweeted about news articles/research (n = 16,761, 22.0%) and risk/prevention (n = 14,767, 19.4%). Medical professional users generated only 2.0% of total tweets (n = 1509), and medical institutions rarely tweeted (n = 417, 0.6%). Organizations tended to tweet more about information than did individuals (85.2% vs 63.1%; P < 0.001). Credibility analysis of medically relevant sample tweets revealed that most were medically correct (n = 1763, 84.5%). Among those, more frequently retweeted tweets contained more medically correct information than randomly selected tweets (90.7% vs 83.2%; P < 0.01). Our results demonstrate an interest in and an engagement with colorectal cancer information from a large number and variety of users. Coupled with the Internet's potential to increase social support, Twitter may contribute to enhancing public health and empowering users, when used with proper caution. PMID- 26886627 TI - A Novel and Validated Inflammation-Based Score (IBS) Predicts Survival in Patients With Hepatocellular Carcinoma Following Curative Surgical Resection: A STROBE-Compliant Article. AB - As chronic inflammation is involved in the pathogenesis and progression of hepatocellular carcinoma (HCC), we investigated the prognostic accuracy of a cluster of inflammatory scores, including the Glasgow Prognostic Score, modified Glasgow Prognostic Score, platelet to lymphocyte ratio, Prognostic Nutritional Index, Prognostic Index, and a novel Inflammation-Based Score (IBS) integrated preoperative and postoperative neutrophil to lymphocyte ratio in 2 independent cohorts. Further, we aimed to formulate an effective prognostic nomogram for HCC after hepatectomy.Prognostic value of inflammatory scores and Barcelona Clinic Liver Cancer (BCLC) stage were studied in a training cohort of 772 patients with HCC underwent hepatectomy. Independent predictors of survival identified in multivariate analysis were validated in an independent set of 349 patients with an overall similar clinical feature.In both training and validation cohorts, IBS, microscopic vascular invasion, and BCLC stage emerged as independent factors of overall survival (OS) and recurrence-free survival (RFS). The predictive capacity of the IBS in both OS and RFS appeared superior to that of the other inflammatory scores in terms of C-index. Additionally, the formulated nomogram comprised IBS resulted in more accurate prognostic prediction compared with BCLC stage alone.IBS is a novel and validated prognostic indicator of HCC after curative resection, and a robust HCC nomogram including IBS was developed to predict survival for patients after hepatectomy. PMID- 26886628 TI - Chinese Herbal Medicine for Symptom Management in Cancer Palliative Care: Systematic Review And Meta-analysis. AB - Use of Chinese herbal medicines (CHM) in symptom management for cancer palliative care is very common in Chinese populations but clinical evidence on their effectiveness is yet to be synthesized. To conduct a systematic review with meta analysis to summarize results from CHM randomized controlled trials (RCTs) focusing on symptoms that are undertreated in conventional cancer palliative care.Five international and 3 Chinese databases were searched. RCTs evaluating CHM, either in combination with conventional treatments or used alone, in managing cancer-related symptoms were considered eligible. Effectiveness was quantified by using weighted mean difference (WMD) using random effect model meta analysis. Fourteen RCTs were included. Compared with conventional intervention alone, meta-analysis showed that combined CHM and conventional treatment significantly reduced pain (3 studies, pooled WMD: -0.90, 95% CI: -1.69 to 0.11). Six trials comparing CHM with conventional medications demonstrated similar effect in reducing constipation. One RCT showed significant positive effect of CHM plus chemotherapy for managing fatigue, but not in the remaining 3 RCTs. The additional use of CHM to chemotherapy does not improve anorexia when compared to chemotherapy alone, but the result was concluded from 2 small trials only. Adverse events were infrequent and mild. CHM may be considered as an add-on to conventional care in the management of pain in cancer patients. CHM could also be considered as an alternative to conventional care for reducing constipation. Evidence on the use of CHM for treating anorexia and fatigue in cancer patients is uncertain, warranting further research. PMID- 26886629 TI - Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature. AB - The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 * 1.5 cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1alpha, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5 , and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined. PMID- 26886630 TI - A Causal Role of Genetically Elevated Circulating Interleukin-10 in the Development of Digestive Cancers: Evidence from Mendelian Randomization Analysis Based on 29,307 Subjects. AB - Recent studies have observed a high level of circulating interleukin-10 (IL-10) in patients with digestive cancers, yet whether elevated IL-10 is causally associated with digestive cancers so far remained unresolved. We therefore meta analyzed available observational studies with Mendelian randomization method to explore this causal association by employing IL-10 gene 3 variants (-592C>A, 819C>T, and -1082A>G) as instruments. Data were available from 52 articles encompassing 29,307 subjects. Subgroup analysis by cancer type indicated that 1082A>G was associated with increased risk of gastric cancer (odds ratio [OR] = 1.19; 95% confidence interval [CI]: 1.05-1.35; P = 0.006), and the association was reinforced for intestinal type gastric cancer (OR = 1.26; 95%CI: 1.09-1.44; P = 0.001). By ethnicity, risk estimate for -1082G allele carriers was increased by 21% for digestive cancers in East Asians (95%CI: 1.05-1.40; P = 0.009). As for the genotype-phenotype association, carriers of -1082G allele had an overall 20.21 pg/mL higher IL-10 level than those with -1082AA genotype (P = 0.023). In further Mendelian randomization analysis, the predicted OR for 10 pg/mL increment in IL-10 was 1.14 (95%CI: 1.01-16.99) in gastric cancer. Our findings provided evidence for a causal role of genetically elevated IL-10 in the development of gastric cancer, especially in East Asians and for intestinal type gastric cancer. PMID- 26886632 TI - Factors Associated With Neck Hematoma After Thyroidectomy: A Retrospective Analysis Using a Japanese Inpatient Database. AB - To identify risk factors for post-thyroidectomy hematoma requiring airway intervention or surgery ("wound hematoma") and determine post-thyroidectomy time to intervention. Post-thyroidectomy hematoma is rare but potentially lethal. Information on wound hematoma in a nationwide clinical setting is scarce.Using the Japanese Diagnosis Procedure Combination database, we extracted data from records of patients undergoing thyroidectomy from July 2010 to March 2014. Patients with clinical stage IV cancer or those with bilateral neck dissection were excluded because they could have undergone planned tracheotomy on the day of thyroidectomy. We assessed the association between background characteristics and wound hematoma <=2 days post-thyroidectomy, using multivariable logistic regression analysis. Among 51,968 patients from 880 hospitals, wound hematoma occurred in 920 (1.8%) <=2 days post-thyroidectomy and in 203 (0.4%) >=3 days post-thyroidectomy (in-hospital mortality = 0.05%). Factors significantly associated with wound hematoma <=2 days post-thyroidectomy were male sex (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.30-1.77); higher age (OR 1.01, 95% CI 1.00-1.02); overweight or obese (OR 1.22, 95% CI 1.04-1.44); type of surgery (partial thyroidectomy for benign tumor compared with: total thyroidectomy, benign tumor [OR 1.95, 95% CI 1.45-2.63]; partial thyroidectomy, malignant tumor [OR 1.21, 95% CI 1.00-1.46]; total thyroidectomy, malignant tumor [OR 2.49, 95% CI 1.82-3.49]; and thyroidectomy for Graves disease [OR 3.88, 95% CI 2.59-5.82]); neck dissection (OR, 1.53, 95% CI 1.05-2.23); antithrombotic agents (OR 1.58, 95% CI 1.15-2.17); and blood transfusion (OR 5.33, 95% CI 2.39 11.91). Closer monitoring of airway and neck is recommended for patients with risk factors, and further cautious monitoring beyond 3 days post-thyroidectomy. PMID- 26886631 TI - Single Nucleotide Polymorphisms and Osteoarthritis: An Overview and a Meta Analysis. AB - Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide polymorphisms (SNPs) are common DNA variants that have shown promising and efficiency, compared with positional cloning, to map candidate genes of complex diseases, including OA. In this study, we aim to provide an overview of multiple SNPs from a number of genes that have recently been linked to OA susceptibility. We also performed a comprehensive meta-analysis to evaluate the association of SNP rs7639618 of double von Willebrand factor A domains (DVWA) gene with OA susceptibility. A systematic search of studies on the association of SNPs with susceptibility to OA was conducted in PubMed and Google scholar. Studies subjected to meta-analysis include human and case-control studies that met the Hardy-Weinberg equilibrium model and provide sufficient data to calculate an odds ratio (OR). A total of 9500 OA cases and 9365 controls in 7 case-control studies relating to SNP rs7639618 were included in this study and the ORs with 95% confidence intervals (CIs) were calculated. Over 50 SNPs from different genes have been shown to be associated with either hip (23), or knee (20), or both (13) OA. The ORs of these SNPs for OA and the subtypes are not consistent. As to SNP rs7639618 of DVWA, increased knee OA risk was observed in all genetic models analyzed. Specifically, people from Asian with G-allele showed significantly increased risk of knee OA (A versus G: OR = 1.28, 95% CI 1.13-1.46; AA versus GG: OR = 1.60, 95% CI 1.25-2.05; GA versus GG: OR = 1.31, 95% CI 1.18-1.44; AA versus GA+GG: OR = 1.34, 95% CI 1.12-1.61; AA+GA versus GG: OR = 1.40, 95% CI 1.19 1.64), but not in Caucasians or with hip OA. Our results suggest that multiple SNPs play different roles in the pathogenesis of OA and its subtypes; SNP rs7639618 of DVWA gene is associated with a significantly increased risk of knee OA in Asians. Given the limited sample size, further studies are needed to evaluate this observation. PMID- 26886634 TI - Tracheobronchial Involvement of Rosai-Dorfman Disease: Case Report and Review of the Literature. AB - Rosai-Dorfman Disease (RDD) is a rare non-neoplastic entity, also known as sinus histiocytosis with massive lymphadenopathy (SHML), characterized by a benign proliferation of histiocytes in lymph nodes. Localized forms of RDD involving the tracheobronchial tree are very rare. There is no consensus regarding the management of central airway forms and recurrence is frequent. We report the case of an 81-year-old Caucasian woman admitted in 2014 for chronic cough. Her main medical past history included a diagnosis of sinonasal RDD in 1996 with recurrent obstructive rhinosinusitis requiring repeated sinonasal surgery, and a diagnosis of tracheal RDD in 2010 with 2 asymptomatic smooth lesions (5 and 7 mm) on the anterior tracheal wall. Physical examination was normal in 2014. Pulmonary function tests showed an obstructive pattern. Computed tomographic scan revealed a mass arising from the anterior wall of the trachea that projects into the tracheal lumen. Fiberoptic bronchoscopy showed a hypervascular multilobular lesion (2 cm) arising from the anterior tracheal wall and causing 50% obstruction of the tracheal lumen. Mechanical resection with electrocoagulation of the tracheal mass was performed by rigid bronchoscopy with no complication. Histological examination demonstrated tracheal RDD. One year after endotracheal resection, the patient presented no recurrence of cough and the obstructive pattern had resolved. Reports on tracheobronchial involvement are scarce. Symptomatic tracheobronchial obstruction requires mechanical resection by rigid bronchoscopy or surgery. Recurrence is frequent, justifying long-term follow-up. PMID- 26886633 TI - Negative Effects of Total Gastrectomy on Bone Tissue Metabolism and Volumetric Bone Mineral Density (vBMD) of Lumbar Spine in 1-Year Study in Men. AB - Gastrectomy induces severe osteoporosis in humans but its quantitative scale within trabecular and cortical compartments was not estimated. The aim of the study was to determine changes of volumetric bone mineral density (vBMD) in lumbar vertebrae (L1-L4) and biochemical bone metabolism markers in serum of patients 1 year after total gastrectomy. The control group consisted of patients (N = 8) subjected to abdominal surgery due to cardiospasmus. Total gastrectomy was performed in the experimental group (N = 6). Volumetric bone mineral density of trabecular and cortical bone of lumbar spine was measured before (baseline) and 1 year after the gastric surgery using the quantitative computed tomography method. Serum concentrations of insulin, insulin-like growth factor-1, tyroxine, interleukin-6, C-terminal telopeptides of type II collagen and bone formation, and resorption markers were determined at baseline and 1 year later, using ELISA, EIA, and IEMA methods. Total gastrectomy induced significant decrease of vBMD values, up to 16.8% and 10.0%, within the trabecular and cortical bone compartments of lumbar spine (P < 0.05). These negative changes of vBMD were associated with significantly increased serum concentration of bone resorption markers such as deoxypyridinoline, pyridinoline, and C-terminal telopeptides of type I collagen, by 13.5%, 32.2%, and 121.5%, respectively (P < 0.05). Neither vBMD nor biochemical bone turnover markers and hormone concentrations were influenced in the control patients. Dramatic bone loss during the first year in gastrectomized patients has proven dynamic osteoporosis progress indicating an importance of treatment interventions in these patients with emphasis on inhibition of intensive bone resorption processes. PMID- 26886635 TI - The Association Between Hyperuricemia and Hematological Indicators in a Chinese Adult Population. AB - The aim of this study was to explore the relationship between hyperuricemia and hematological indicators. Five hundred twenty-two male and 255 female subjects (18-90 years old) were recruited in the study. The level of serum uric acid (SUA), total white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit, and platelet count was measured, computed, and analyzed. Pearson correlation coefficients, Student t-tests, multivariate linear regression models, and multivariate logistic regression models were performed to analyze the results.For men, WBC count (r = 0.13, P < 0.01), RBC count (r = 0.15, P < 0.001), and hemoglobin (r = 0.11, P < 0.05) were significantly correlated with SUA. For women, WBC count (r = 0.24, P < 0.001), RBC count (r = 0.31, P < 0.001), hemoglobin (r = 0.31, P < 0.001), and hematocrit (r = 0.29, P < 0.001) were significantly correlated with SUA. For men, WBC (P < 0.01) and RBC (P < 0.05) counts were significantly higher in patients with hyperuricemia than in normal subjects. For men, after adjustment for confounding factors, those in the fourth quartiles of WBC counts had 1.66-fold increased odds of hyperuricemia as compared with those in the reference group. For women, after adjustment, those in the second to fourth quartiles of WBC count, RBC count, hemoglobin, and hematocrit had increased the odds of hyperuricemia as compared with those in the reference groups. Our study showed significant relations between the level of SUA and WBC count, RBC count, hemoglobin, and hematocrit, which could be important biological markers of hyperuricemia. PMID- 26886636 TI - Spectral CT in the Demonstration of the Pancreatic Arteries and Their Branches: A Comparison With Conventional CT. AB - The aim of this study was to investigate the performance of monochromatic images of spectral computed tomographic (CT) in the visualization of the pancreatic arteries compared with polychromatic CT images. We conducted a case-control study in a group of 26 consecutive patients with monochromatic CT and contrasted the results against a control group of 26 consecutive patients with polychromatic CT. The CNR (contrast-to-noise ratio), SIR (signal intensity ratio), SNR (signal to noise ratio), and image noise were measured. A 5-score classification system was used to evaluate the branch order of pancreatic arteries. The course of pancreatic arteries was compared. Compared with polychromatic images, the CNR, SIR, and SNR obtained by monochromatic images were increased by 64.74%, 23.99%, and 39.50%. Branch visualization of PSPDA (posterior superior pancreaticoduodenal artery), ASPDA (anterior superior pancreaticoduodenal artery), and DPA (dorsal pancreatic artery) was better at monochromatic images than at polychromatic images. The display rate was significantly better in monochromatic images for the second and third segments of PSPDA, total course of ASPDA, and artery of uncinate process. Compared with polychromatic images, monochromatic images can improve the visualization of pancreatic arteries. PMID- 26886637 TI - Phase II Randomized Controlled Trial of Combined Oral laxatives Medication for BOwel PREParation (COMBO-PREP study). AB - The combination of different laxatives at reduced volumes may benefit patients by enhancing efficacy for bowel cleansing and increasing tolerability. However, evidence regarding combined preparations is scarce. This study evaluated whether the combined preparations are associated with enhanced efficacy and tolerability. This randomized phase II study had a single-blind, parallel-arm design. Between December 2013 and September 2014, consecutive patients aged between 20 and 65 years and who required diagnostic colonoscopies were considered for inclusion. Patients were randomly allocated into 4 arms: sodium picosulfate and magnesium citrate (PMC) and polyethylene glycol (PEG) with ascorbic acid in a day-prior (PMC-PEG-DP), PMC and oral sodium phosphate (NaP) in a day-prior (PMC-NaP-DP), PMC and PEG with ascorbic acid in a split-dose (PMC-PEG-SD), and PMC and oral NaP in a split-dose (PMC-NaP-SD). Primary endpoint was the Aronchick scale, and Ottawa scale results by colon segment, patients' adverse gastrointestinal symptoms, and willingness to reuse the same agents were also recorded. Successful bowel preparation was defined as an "excellent" or "good" score on the Aronchick scale. A total of 236 patients were randomized and 229 patients received the planned colonoscopy. The rates of successful bowel preparation in the PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD were 82.5%, 64.4%, 100%, and 100%, respectively. Excluding the failed PMC-NaP-DP group, all groups showed satisfactory rates of successful bowel preparation, and the mean Ottawa scores were significantly better in the PMC-PEG-SD and PMC-NaP-SD groups than in the PMC PEG-DP group (P < 0.0001). The PMC-PEG-DP, PMC-NaP-DP, PMC-PEG-SD, and PMC-NaP-SD groups were similar in terms of rates of adverse gastrointestinal symptoms reported on a 5-point scale (P = 0.40) and willingness to reuse the same combined preparations (P = 0.55). PMC-PEG in a day-prior or split-dose and PMC-NaP in a split-dose were efficient and tolerable bowel preparations for colonoscopy. PMID- 26886638 TI - The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR 608 With Breast Cancer Susceptibility: A STROBE-Compliant Observational Study. AB - MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52-0.86), recessive (OR = 0.65, 95% CI = 0.48-0.86), and allele models (OR = 0.73, 95% CI = 0.62-0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10 1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals. PMID- 26886639 TI - Impact of Intracranial Pressure Monitoring on Prognosis of Patients With Severe Traumatic Brain Injury: A PRISMA Systematic Review and Meta-Analysis. AB - To evaluate the influences of using intracranial pressure (ICP) monitoring on the prognosis of patients with severe traumatic brain injury. Systematic search were conducted in PubMed, Embase, Cochrane Library, Wanfang, and CNKI. The eligible studies were identified for pooling analysis under fixed- or random effects model. Hospital mortality, functional outcomes, length of hospital stay, and the related complications in patients were extracted. Six randomized controlled trials with 880 cases and 12 cohort studies with 12,606 cases were included. Combined analysis found that ICP monitoring was effective for reducing the risk rate of electrolyte disturbances (RR = 0.47, 95% confidence interval (CI): 0.63 0.90), rate of renal failure (RR = 0.50, 95% CI: 0.30-0.83), and for improving favorable prognosis (RR = 1.15, 95% CI: 1.00-1.35). However, ICP monitoring was not significant for hospital mortality (RR = 0.91, 95% CI: 0.77-0.1.06), decreasing rate of pulmonary infection (RR = 0.93, 95% CI: 0.76-1.14), rate of mechanical ventilation (RR = 1.02, 95% CI: 0.86-1.09), and duration of hospital stays (weighted mean difference (WMD) = 0.06, 95% CI: -0.03, 0.16). ICP monitoring may not reduce the risk of hospital mortality, but plays a role in decreasing the rate of electrolyte disturbances, rate of renal failure, and increasing favorable functional outcome. However, effect of other outcomes need to be further confirmed in the future randomized controlled trials (RCTs) with larger sample size. PMID- 26886640 TI - CD34 Over-Expression is Associated With Gliomas' Higher WHO Grade. AB - CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta analysis is the best choice for drawing a convincing conclusion. Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas' WHO grades, patients' ages and gender. We used the Galbraith figure, the I test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results' stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments. There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot. Our results suggested that CD34 overexpression is associated with higher WHO grades of gliomas. CD34 may serve as a potential diagnostic and prognostic marker, or it could be a useful therapy target. PMID- 26886641 TI - Unusual Presentation of Elastofibroma Dorsi on 18F-FDG-PET/CT: A Case Report. AB - A 70-year-old male patient underwent an Fluorodeoxyglucose-positron emission tomography-computed tomography for staging of a left parahilar lung neoplasm found during work-up for fatigue and asthenia. The scan demonstrated a hypermetabolic lung tumor, a hypermetabolic pleural effusion and 4 hypermetabolic bilateral soft tissue lesions of the chest wall corresponding to 4 elastofibroma dorsi. Initially, the oncologic disease was classified as stage IV because of the hypermetabolic pleural effusion. A transbronchial biopsy showed squamous cell carcinoma and the cytology of the pleural effusion revealed no malignant cells. As the other 4 hypermetabolic thoracic wall lesions were correctly diagnosed as benign despite their unusual presentation, the patient underwent surgery by left pneumonectomy and mediastinal lymphadenectomy. The lymph node involvement required adjuvant chemotherapy. Diagnostic confidence of the benignity of the hypermetabolic chest wall lesions allowed a more aggressive treatment with a better outcome after a malignant pleural effusion was excluded. PMID- 26886642 TI - Association Between Glaucoma and the Risk of Dementia. AB - We investigated the association of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) with the risk of dementia by evaluating their clinical and epidemiological similarities by using a nationally representative sample in Taiwan. Data were collected from the National Health Insurance Research Database of Taiwan. In total, 6509 patients with glaucoma (3304 with POAG and 3205 with PACG) were enrolled, and a comparison cohort of 26,036 individuals without glaucoma was established after matching for age and sex. The cumulative incidence curve of overall dementia for each cohort was evaluated. The risk of dementia was analyzed using univariate and multivariate Cox proportional hazard models after adjustment for demographic characteristics and comorbidities. The patients with glaucoma exhibited a significantly higher risk of dementia than the individuals without glaucoma did (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.01-1.27). The patients with POAG exhibited a 1.21-fold increased risk of dementia compared with the individuals without glaucoma (HR = 1.21, 95% CI = 1.02-1.43). However, the patients with PACG were not significantly associated with an increased risk of dementia compared with the individuals without glaucoma (HR = 1.09, 95% CI = 0.95-1.26). Patients with POAG aged >=65 years were significantly associated with an increased risk of dementia compared with the individuals without glaucoma (HR = 1.28, 95% CI = 1.07-1.54). Females with POAG exhibited a 1.34-fold increased risk of dementia compared with females without glaucoma (95% CI = 1.06-1.69). This study demonstrated that patients with POAG but not those with PACG were associated with an increased risk of dementia compared with the general population. PMID- 26886643 TI - Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports. AB - Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed. PMID- 26886644 TI - Differences and Similarities in the Clinicopathological Features of Pancreatic Neuroendocrine Tumors in China and the United States: A Multicenter Study. AB - The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with unfavorable survival in both countries. Several clinicopathological differences are found between Chinese and US PNETs but the PNETs of both countries follow a similar natural history. The WHO tumor grading and ENETS staging criteria are applicable to both Chinese and US patients. PMID- 26886645 TI - LV Dyssynchrony Is Helpful in Predicting Ventricular Arrhythmia in Ischemic Cardiomyopathy After Cardiac Resynchronization Therapy: A Preliminary Study. AB - For patients with coronary artery disease, larger scar burdens are associated with higher risk of ventricular arrhythmia. Left ventricular (LV) dyssynchrony is associated with increased risk of sudden cardiac death in patients with heart failure. The purpose of this study was to assess the values of LV dyssynchrony and myocardial scar assessed by myocardial perfusion SPECT (MPS) in predicting the development of ventricular arrhythmia in ischemic cardiomyopathy. Twenty-two patients (16 males, mean age: 66 +/- 13) with irreversible ischemic cardiomyopathy received cardiac resynchronization therapy (CRT) for at least 12 months were enrolled for MPS. Quantitative parameters, including LV dyssynchrony with phase standard deviation (phase SD) and bandwidth, left ventricular ejection fraction (LVEF), and scar (% of total areas), were generated by Emory Cardiac Toolbox. Ventricular tachycardia (VT) and ventricular fibrillation (VF) recorded in the CRT device during follow-up were used as the reference standard of diagnosing ventricular arrhythmia. Stepwise logistic regression analysis was performed for determining the independent predictors of VT/VF and receiver operating characteristic (ROC) curve analysis was used for generating the optimal cut-off values for predicting VT/VF. Nine (41%) of the 22 patients developed VT/VF during the follow-up periods. Patients with VT/VF had significantly lower LVEF, larger scar, larger phase SD, and larger bandwidth (all P < 0.05). Logistic regression analysis showed LVEF and bandwidth were independent predictors of VT/VF. ROC curve analysis showed the areas under the curves were 0.71 and 0.83 for LVEF and bandwidth, respectively. The optimal cut-off values were <36% and > 139 degrees for LVEF and bandwidth, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 39%, 53%, and 100%, respectively, for LVEF; and were 78%, 92%, 88%, and 86%, respectively, for bandwidth. LV dyssynchrony as assessed by phase analysis of MPS is helpful for predicting ventricular arrhythmia in ischemic cardiomyopathy after CRT. Further implantation of defibrillator may be considered for those patients with bandwidth >139 degrees . PMID- 26886646 TI - Prediction of Large Joint Destruction in Patients With Rheumatoid Arthritis Using 18F-FDG PET/CT and Disease Activity Score. AB - The assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee, and ankle. Few studies have been reported regarding the degree of large joint destruction in RA patients. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) visualizes the disease activity in large joints affected by RA. In this study, the associations between destruction of the large joints and the findings of FDG PET/CT as well as laboratory parameters were investigated, and factors associated with large joint destruction after the administration of biological therapy were identified in RA patients. A total of 264 large joints in 23 RA patients (6 men and 17 women; mean age of 66.9 +/- 7.9 years) were assessed in this study. FDG PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The extent of FDG uptake in large joints (shoulder, elbow, wrist, hip, knee, and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient obtained at baseline and after 2 years were assessed according to Larsen's method. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within 2 years. Radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and 6 months, and the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) at 6, 12, and 24 months were significantly higher in the group with progressive joint destruction. The SUVmax at baseline and DAS28-ESR at 6 months were found to be factors associated with joint destruction at 2 years (P < 0.05). The FDG uptake in the joints with destruction was higher than that observed in the joints without destruction. The SUVmax at baseline and the DAS28-ESR at 6 months after the biological treatment were identified to be significant factors predicting destruction of the large joints at 2 years. PMID- 26886647 TI - Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan. AB - The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age <20 years, missing sex data, docetaxel use during or after RT, induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose <7000 cGy, curative head and neck cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III-IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22-1.53) and 1.44 (1.36-1.52) in arms 2 and 3, respectively. In a disease specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1.14-1.46) and 1.47 (1.38-1.56) in arms 2 and 3, respectively. Compared with CCRT alone, docetaxal- or platinum-based induction CT did not improve survival but increased the risk of all-cause and head and neck cancer related death. PMID- 26886648 TI - Factors Associated With Mortality of Thyroid Storm: Analysis Using a National Inpatient Database in Japan. AB - Thyroid storm is a life-threatening and emergent manifestation of thyrotoxicosis. However, predictive features associated with fatal outcomes in this crisis have not been clearly defined because of its rarity. The objective of this study was to investigate the associations of patient characteristics, treatments, and comorbidities with in-hospital mortality. We conducted a retrospective observational study of patients diagnosed with thyroid storm using a national inpatient database in Japan from April 1, 2011 to March 31, 2014. Of approximately 21 million inpatients in the database, we identified 1324 patients diagnosed with thyroid storm. The mean (standard deviation) age was 47 (18) years, and 943 (71.3%) patients were female. The overall in-hospital mortality was 10.1%. The number of patients was highest in the summer season. The most common comorbidity at admission was cardiovascular diseases (46.6%). Multivariable logistic regression analyses showed that higher mortality was significantly associated with older age (>=60 years), central nervous system dysfunction at admission, nonuse of antithyroid drugs and beta-blockade, and requirement for mechanical ventilation and therapeutic plasma exchange combined with hemodialysis. The present study identified clinical features associated with mortality of thyroid storm using large-scale data. Physicians should pay special attention to older patients with thyrotoxicosis and coexisting central nervous system dysfunction. Future prospective studies are needed to clarify treatment options that could improve the survival outcomes of thyroid storm. PMID- 26886649 TI - Comparison of Effects of Botulinum Toxin Injection Between Subacute and Chronic Stroke Patients: A Pilot Study. AB - The aim of this study was to compare the effects of botulinum toxin injection between subacute and chronic stroke patients. Eighteen stroke patients (9 subacute and 9 chronic) with spasticity of 1+ or higher in the hemiplegic elbow or wrist joint, based on the modified Ashworth scale were recruited. Modified Ashworth scale, modified Tardieu scale, manual muscle testing, passive range of motion, Brunnstrom stage, modified Barthel index, and Fugl-Meyer scale evaluations of the hemiplegic upper extremity were performed just before the injection and 4 weeks later. A total dose of 200 U of botulinum toxin type A was injected into each patient. One or more of the elbow flexor muscles and one or more of the wrist flexor or finger flexor muscles were included. Modified Ashworth scale, manual muscle testing, passive range of motion, and modified Barthel index results were improved in subacute patients only. However, modified Tardieu scale for the elbow and Fugl-Meyer scale results were improved in both groups, and the improvement was comparable. In conclusion, botulinum toxin injection in subacute patients was more helpful for spasticity, contracture, and function than in chronic patients. However, beneficial effects of botulinum toxin injection on spasticity and function in chronic patients were found in the assessments of the modified Tardieu scale and Fugl-Meyer scale. PMID- 26886650 TI - DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins. AB - IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules. Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n = 5), chronic sialoadenitis (CS) (n = 3), and controls (n = 3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n = 18), CS (n = 4), Sjogren syndrome (n = 11), and controls (n = 10). Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P < 0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P < 0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163. MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO. PMID- 26886651 TI - Intraoperative Dexmedetomidine Improves the Quality of Recovery and Postoperative Pulmonary Function in Patients Undergoing Video-assisted Thoracoscopic Surgery: A CONSORT-Prospective, Randomized, Controlled Trial. AB - Video-assisted thoracoscopic surgery (VATS) has been known to be a stressful event for patients, and dexmedetomidine is known to attenuate surgery-induced sympathetic responses and potentiate analgesia in perioperative periods. The present was designed to evaluate the effects of intraoperative dexmedetomidine administration on the quality of recovery (QoR) and pulmonary function after VATS. Patients with lung cancer undergoing VATS were randomized to Dex group (loading of 1.0 MUg/kg for 20 minutes before the termination of surgery, n = 50) or Control group (comparable volume of normal saline, n = 50). The QoR-40 questionnaire assesses postoperative recovery and validates the overall surgical and general anesthesia outcomes. The QoR-40 scores, forced expiratory volume for 1 second (FEV1) on postoperative day (POD) 1 and 2, and emergence agitation were evaluated. The global QoR-40 score (162.3 +/- 17.8 vs 153.3 +/- 18.7, P = 0.016 on POD 1; 174.3 +/- 16.0 vs 166.8 +/- 16.7, P = 0.028 on POD 2) and FEV1 (2.1 +/- 0.4 vs 1.9 +/- 0.5 L, P = 0.034 on POD 1; 2.2 +/- 0.5 vs 2.0 +/- 0.4 L, P = 0.030 on POD 2) were significantly higher in the Dex group compared with the Control group on POD1 and POD 2. The score of emergence agitation was lower in the Dex group compared with the Control group (3 [2-5] vs 5 [3-7], P < 0.001). The number of patients indicating severe emergence agitation was shorter in the Dex group than Control group (0 [0%] vs 7 [14%], P = 0.048). The length of hospital stay was significantly shorter (6.7 [3-9] vs 8.4 [4-9] days, P = 0.045) in the Dex group compared with the Control group. Intraoperative dexmedetomidine administration improved QoR, postoperative pulmonary function, and emergence agitation in patients undergoing VATS. Consequently, intraoperative dexmedetomidine administration could improve postoperative outcomes and reduced the length of hospital stay in patients undergoing VATS. PMID- 26886652 TI - Rapid Early Triage by Leukocytosis and the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: An Observational Study. AB - The clinical utility of leukocytosis in risk assessment for ST-elevation myocardial infarction (STEMI) is still unclear. We aim to demonstrate the prognostic value of leukocyte counts independent from traditional risk factors and the TIMI risk score (TRS) for STEMI and to propose a practical model comprising leukocyte count for early triage in STEMI undergoing primary angioplasty. A prospective database (n = 796) of consecutive STEMI cases receiving primary angioplasty at a tertiary medical center was retrospectively analyzed in the period from February 1, 2007 through December 31, 2012. Primary endpoints were 30-day and 1-year mortality. Propensity score-adjusted Cox regression models and subdivision analysis were performed. Leukocytosis group (n = 306) had higher 30-day mortality (5.9% vs 3.1%, P = 0.048) and 1-year mortality (9.2% vs 5.1%, P = 0.022). After adjustment by propensity score and TRS, leukocyte count (per 10/MUL) was an independent predictor of 1-year mortality (HR: 1.086, 95% CI: 1.034-1.140, P = 0.001). Subdivision analysis demonstrated the correlation between leukocytosis and higher 1-year mortality within both high and low TRS strata (divided by 4, the median of TRS). Additionally, 24% (191 out of 796) of patients were characterized by nonleukocytosis and TRS < 4, having 0% of mortality rate at 1-year follow-up. In conclusion, leukocyte count is an independent prognostic factor adding incremental value to TRS for STEMI. Nonleukocytosis in conjunction with TRS < 4 identifies a large patient group at extremely low risk and thus provides rapid early triage for STEMI patients undergoing primary PCI. This finding is worth validation in the future. PMID- 26886653 TI - Comparison of Elixhauser and Charlson Methods for Predicting Oral Cancer Survival. AB - Cancer survival correlates not only with the features of primary malignancy but also with the degree of underlying comorbidities. Of the multiple methods used for evaluating the impact of comorbidities on survival, the Charlson and Elixhauser methods are most common. This study compared these 2 comorbidity measures for predicting survival in oral cancer patients. Using the Taiwan National Health Insurance claims data (2008-2011), we acquired data regarding patients' characteristics, comorbidities, and survival from 3583 oral cancer patients. Comorbidity was classified according to both the Charlson comorbidity and Elixhauser comorbidity based on the International Classification of Diseases, 9th Revision. The Elixhauser comorbidity score and Charlson comorbidity score were also calculated. The prediction of survival was determined using measures of discrimination, including the Akaike information criterion and Harrell C (C statistic). The mean age of the study cohort was 52 +/- 10 years, and 94.9% of the patients were male. The median follow-up time was 30.1 months, and the 3-year overall survival was 61.6%. Elixhauser comorbidity method added higher discrimination, compared with the Charlson comorbidity method (Harrell C, 0.677 vs 0.651). Furthermore, the Elixhauser comorbidity score outperformed the Charlson comorbidity score in continuous variable (Harrell C, 0.654 vs 0.646) and category (Harrell C, 0.658 vs 0.645). The Elixhauser method is a superior comorbidity risk-adjustment model for oral cancer survival prediction. Utilization of the Elixhauser comorbidity method may be encouraged for risk adjustment in oral cancer study. PMID- 26886654 TI - Clinicopathological Differences and Prognostic Value of Hypoxia-Inducible Factor 2alpha Expression for Gastric Cancer: Evidence From Meta-Analysis. AB - Published literatures have reported the relationship between hypoxic-inducible factor-2alpha (HIF-2alpha) expression and clinicopathological features in gastric cancer (GC), but the evaluated conclusions remain controversial. A meta-analysis was carried to examine the clinicopathological features and prognostic values of HIF-2alpha in patients with GC. Systematic detailed searches were performed to Pub Med, Cochrane Library, and EBSCO until to August 2015. Six studies (508 specimens) were included in this meta-analysis. HIF-2alpha-positive expression indicates an unfavorable prognosis value and advanced clinicopathological differences for the available patient dates with GC. Further multivariate meta analysis revealed that HIF-2alpha-positive expression in gastric cancer associated with deeper tumor infiltration (OR = 3.08; 95%CI: 1.18-8.04), higher rates of lymphatic metastasis (OR = 3.26; 95%CI: 1.10-9.63), higher TNM stage (III+IV) (OR = 2.61; 95%CI: 1.40-4.84), and much lower 5-year overall survival (OR = 2.08; 95%CI: 1.21-3.58). Nevertheless, there is no association between HIF 2alpha-positive expression and worse tumor differentiation (OR = 2.03; 95%CI: 0.73-5.64). In addition, by this subgroup analysis, HIF-2alpha-positive expression associated with deeper tumor infiltration (OR = 3.81; 95%CI: 1.03 14.08), higher lymphatic metastasis (OR = 4.71; 95%CI: 1.08-20.50), higher TNM stage (OR = 3.21; 95%CI: 1.57-6.57), worse tumor differentiation (OR = 3.08; 95%CI: 1.51-6.31), and lower 5-year overall survival (OR = 2.34; 95%CI: 1.15 4.79). Our results indicate that HIF-2alpha overexpression can potently predict the poor prognosis and may be a potential therapeutic target for gastric carcinoma, according to the limited evidence. Meanwhile, further studies are needed to elucidate the accuracy of these results. PMID- 26886655 TI - Meta-Analysis of the Effects of Xingnaojing Injection on Consciousness Disturbance. AB - Xingnaojing (XNJ) is commonly extracted from Angongniuhuang, a classic Chinese emergency prescription, and widely used in the treatment of nervous system disorders including consciousness disturbance in China. To evaluate the beneficial and adverse effects of XNJ injection, on consciousness disturbance. Seven major electronic databases were searched to retrieve randomized controlled trials designed to evaluate the clinical efficacy of XNJ alone or combined with Western medicine in treating consciousness disturbance caused by conditions such as high fever, poisoning, and stroke. The methodological quality of the included studies was assessed using criteria from the Cochrane Handbook for Systematic Review of Interventions, and analyzed using the RevMan 5.3.0 software. Seventeen randomized controlled trials on XNJ were included in this study and the trials generally showed low methodological quality. The results revealed that XNJ alone or in combination with other medicines and adjuvant methods had a positive effect on patients with fever-, poisoning-, and stroke-induced coma. XNJ effectively treated consciousness disturbances that were caused by high fever, poisoning, or stroke. PMID- 26886656 TI - Growth of rare minnows (Gobiocypris rarus) fed different amounts of dietary protein and lipids. AB - The rare minnow (Gobiocypris rarus) is a laboratory fish that is commonly used for toxicology research, but there is currently no standard lab diet for this model organism. Certain studies with rare minnows require specialized diets, so there is a need to better understand how manipulating nutrients affects the development and growth of this fish. We conducted two separate dose-response experiments to determine the effect of different levels of dietary protein or dietary lipids on the growth of juvenile rare minnows over 60 d. We measured growth rates and food intake over two periods of time: the first 20 or 30 d of diet consumption and the entire 60 d of each experiment. We found that different levels of dietary protein or dietary lipids produced significantly different growth rates during both the early phase and the entire duration of the study. Among experimental protein-variable diets, those with intermediate levels of dietary protein (around 35.2%) produced the highest growth rate. Among experimental lipid-variable diets, those with intermediate levels of dietary lipids (around 7.6%) produced the highest growth rate. Over all periods of both experiments, however, the control diet of bloodworms generally produced the highest growth rate that matched or exceeded that of any experimental diet. These results can guide investigators when using rare minnows in research, particularly when using custom and standardized diets. PMID- 26886657 TI - Collection of untainted urinary specimens from the bladder of an anesthetized rabbit. AB - It is difficult to collect untainted urine specimens over short intervals of time during renal studies with rabbits. This is because both the ureters and the bladder of this species are relatively friable and minor manipulation can easily cause intraluminal bleeding. We have developed and refined an effective technique and protocol for placing an indwelling urinary bladder catheter into an anesthetized rabbit. The procedure is easy to perform and completely effective and reliable, allowing high-quality urinary specimens to be collected at intervals of 15-20 min over a period of 3-4 hours during a study of acute metabolic acidosis. PMID- 26886660 TI - CRISPR/Cas9 corrects retinal dystrophy in rats. PMID- 26886661 TI - Amputated amphibians advance regenerative medicine. PMID- 26886663 TI - Breaking down barriers to treating rheumatoid arthritis. PMID- 26886664 TI - Vervets reveal a cause of neurodegeneration. PMID- 26886665 TI - CRISPR/Cas9 and the future of clinical research. PMID- 26886667 TI - Longevity in a fish bowl. PMID- 26886668 TI - Response to Protocol Review Scenario: Consider the circumstances. PMID- 26886669 TI - Setting sights on gunshot training. PMID- 26886670 TI - A word from USDA. PMID- 26886671 TI - Response to Protocol Review Scenario: The details are what matter. PMID- 26886672 TI - Response to Protocol Review Scenario: More comprehensive training is necessary. PMID- 26886673 TI - Methods for measuring pain in laboratory animals. AB - Pain is one of the most important variables that members of the lab animal science community try to control and minimize, and it is a critical topic of research in clinical and basic sciences. Objective measurements of pain severity, especially in non-verbal animals that are used as disease models, can be difficult to obtain, but several developments in behavioral neuroscience are making the measurement of pain more consistent, automated and accurate. PMID- 26886675 TI - Lessons learned from implementing new technology as a trainer. PMID- 26886676 TI - The last airline flying. PMID- 26886677 TI - Fulfilling a lifelong dream. PMID- 26886678 TI - Erratum: Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently. PMID- 26886679 TI - Multilayered film microreactors fabricated by a one-step thermal bonding technique with high reproducibility and their applications. AB - We report the versatile uses of multilayered polyimide (PI) film microreactors with various functions including pressure tolerance, three-dimensional mixing and multistep membrane emulsification. Such PI film microreactors were fabricated by a simple one-step thermal bonding technique with high reproducibility. Upon bonding at 300 degrees C for 1 hour, the thin and flexible film microdevices could withstand pressure up to 8.6 MPa and 16.3 MPa with PI adhesive film or fluoropolymer adhesive, respectively, due to differences in wettability. The hydrophilic and hydrophobic microchannel devices were used to generate monodisperse oil-in-water (O/W) and water-in-oil (W/O) droplets, and polymer micro/nanoparticles at a high generation frequency. A monolithic and chemical resistant film microreactor with a three-dimensional serpentine microchannel was used for the selective reduction of ester to aldehyde by efficient mixing and quenching in a flash chemistry manner, within a several 10(1) millisecond time scale. Furthermore, a novel multilayered film microreactor for organic-aqueous biphasic interfacial reactions was devised by embedding a membrane layer to induce chaotic mixing in both the interface and emulsified phase by flowing through multiple numbers of meshed structures along the hydrophobic channel. This simple and economic fabrication technique significantly facilitates mass production of multilayered film devices that could be useful as a platform for various microfluidic applications in chemistry and biology. PMID- 26886680 TI - Nurses' Experiences of an Initial and Reimplemented Electronic Health Record Use. AB - The electronic health record is a key component of healthcare information systems. Currently, numerous hospitals have adopted electronic health records to replace paper-based records to document care processes and improve care quality. Integrating healthcare information system into traditional nursing daily operations requires time and effort for nurses to become familiarized with this new technology. In the stages of electronic health record implementation, smooth adoption can streamline clinical nursing activities. In order to explore the adoption process, a descriptive qualitative study design and focus group interviews were conducted 3 months after and 2 years after electronic health record system implementation (system aborted 1 year in between) in one hospital located in southern Taiwan. Content analysis was performed to analyze the interview data, and six main themes were derived, in the first stage: (1) liability, work stress, and anticipation for electronic health record; (2) slow network speed, user-unfriendly design for learning process; (3) insufficient information technology/organization support; on the second stage: (4) getting used to electronic health record and further system requirements, (5) benefits of electronic health record in time saving and documentation, (6) unrealistic information technology competence expectation and future use. It concluded that user-friendly design and support by informatics technology and manpower backup would facilitate this adoption process as well. PMID- 26886682 TI - The extent of medication errors and adverse drug reactions throughout the patient journey in acute care in Australia. AB - AIM: To provide an estimate of the numbers of medication errors and adverse drug reactions that occur along a person's journey through their hospital stay in Australia. METHODS: A search of databases and online resources was undertaken to identify published literature on medication safety in the acute care setting in Australia from 2008 to 2013. Data on the rates of adverse drug reactions and medication errors associated with hospitalization was extracted from the published studies. This evidence was synthesized with evidence from previous reviews of medication safety in the acute care setting in Australia conducted in 2002 and 2008. RESULTS: Findings from the Australian literature across the two previous reviews of medication safety and the present review indicate the proportion of all hospital admissions that are medication-related is between 2 and 3%. Studies assessing medication errors on admission to hospital suggest there may be an overall rate of two errors for every three patients at the time of admission to hospital. Large studies examining the rates of prescribing errors in major Australian teaching hospitals give insight into the rates of prescription error and suggest that prescription error rates of up to one error per patient occur in the hospital system. The best available evidence from more recent research suggests that errors (excluding errors of timing) occur in around 9% of medication administrations in hospital. At hospital discharge, errors in medication documentation in discharge summaries may occur at a rate of up to two errors per patient. CONCLUSIONS: Medication safety in the various stages of the patient journey through acute care in Australia continues to be a significant problem. However, the extent of medication-related problems in acute care needs to be interpreted within the context of increasingly complex health care. There are an estimated 230 000 medication-related hospital admissions occurring per year. This suggests an annual cost of medication-related admissions of AU$1.2 billion. PMID- 26886681 TI - Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties. AB - Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison. PMID- 26886683 TI - Self-management for patients with chronic obstructive pulmonary disease. PMID- 26886684 TI - Erratum to: Islet Xeno/transplantation and the risk of contagion: local responses from Canada and Australia to an emerging global technoscience. PMID- 26886685 TI - The Prevalence of Vitreomacular Interface Pathology in a Spanish Tertiary Hospital. AB - PURPOSE: To determine the prevalence of vitreomacular interface (VMI) pathology, using spectral-domain optical coherence tomography (SD-OCT). METHODS: VMI status was classified into macular posterior vitreous detachment (PVD), focal vitreomacular adhesion (VMA; <=1,500 MUm), broad VMA (>1,500 MUm), focal vitreomacular traction (VMT; <=1,500 MUm), broad VMT (>1,500 MUm), full-thickness macular hole (FTMH) with the presence of VMT, and FTMH without the presence of VMT. RESULTS: A total of 1,976 eyes were included. A nonpathologic VMI was observed in 1,875 eyes (94.8%), including 1,050 (53.1%) with PVD, 120 (6.1%) with focal VMA and 705 (35.6%) with broad VMA. A pathologic state of the VMI was diagnosed in 101 eyes (5.1%). Thirty-three eyes (1.7%) were classified as focal VMT, 29 (1.4%) as broad VMT, 39 (1.9%) as FTMH, resulting in 6 small, 12 medium and 21 large FTMHs, six eyes had VMT associated to FTMH. CONCLUSIONS: Even in a tertiary care, retinal referral practice, VMI pathology is a relatively rare condition. There was a higher prevalence in a tertiary hospital study compared to population-based studies. PMID- 26886686 TI - How stereotypes and attitudes toward older adults are challenged through intergenerational contact: Young people explain the process. AB - There is a growing body of evidence on the effectiveness of intergenerational contact in challenging stereotypes and attitudes, particularly when applying the four conditions of Allport's contact hypothesis. Despite this, little is known of how change actually occurs, particularly among young people. Individual interviews with twelve young people (age 11-12 years) were conducted to determine the extent and process by which their stereotypes and attitudes toward older adults (aged 65+) changed through intergenerational contact based on the contact hypothesis. Data analysis revealed five themes and 12 subthemes that illustrate this process. The findings support the contact hypothesis, explain how change occurs, and point to the need for further research on the change process. PMID- 26886687 TI - Parvovirus infection in early arthritis. AB - OBJECTIVES: To analyse the subgroup of early arthritis patients with new onset parvovirus infections for details that may help narrow the population tested. METHODS: From their routine patient charts, patient histories and clinical and serological data were obtained for all 130 patients of the Rheumatology division with parvovirus serology performed. 11 patients had acute parvovirus infections, defined by specific IgM antibodies. 95 patients had a previous infection, 16 were never infected, together forming the n=111 control group, and 8 patients had to be excluded. RESULTS: Most patients with acute parvovirus infection had an acute onset, highly symmetrical polyarthritis of small joints, which was preceded by prodromal symptoms. Positive ANA were frequently found, whereas C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were only mildly elevated. No frank synovitis was found longer than two weeks after disease onset. Most patients were free of symptoms within three months, and no patient in the parvovirus group developed rheumatoid arthritis or a connective tissue disease. CONCLUSIONS: Parvovirus serology may be helpful in patients with acute polyarthritis of very recent onset, and if they give a history of prodromal symptoms, in particular. In most instances, parvovirus arthritis is an acute disease, which is rapidly self-limiting. PMID- 26886688 TI - Mapping intermolecular interactions and active site conformations: from human MMP 1 crystal structure to molecular dynamics free energy calculations. AB - The zinc-dependent Matrix Metalloproteinases (MMPs) found within the extracellular matrix (ECM) of vertebrates are linked to pathological processes such as arthritis, skin ulceration and cancer. Although a general backbone proteolytic mechanism is understood, crystallographic data continue to suggest an active site that is too narrow to encompass the respective substrate. We present a fully parameterised Molecular Dynamics (MD) study of the structural properties of an MMP-1-collagen crystallographic structure (Protein Data Bank - 4AUO), followed by an exploration of the free energy surface of a collagen polypeptide chain entering the active site, using a combined meta-dynamics and umbrella sampling (MDUS) approach. We conclude that the interactions between MMP-1 and the collagen substrate are in good agreement with a number of experimental studies. As such, our unrestrained MD simulations and our MDUS results, which indicate an energetic barrier for a local uncoiling and insertion event, can inform future investigations of the collagen-peptide non-bonded association steps with the active site prior to proteolytic mechanisms. The elucidation of such free energy barriers provides a better understanding of the role of the enzyme in the ECM and is important in the design of future MMP inhibitors. PMID- 26886689 TI - Analysis of chronic myelogenous leukemia in an underserved, inner-city cohort shows a significant five year overall survival that is not affected by choice of tyrosine kinase inhibitor. PMID- 26886690 TI - Not the Last Word: Morbidity and Mortality Conference: Theater of Education. PMID- 26886691 TI - [Migraine - best possible management of an irritating lifelong partner]. PMID- 26886692 TI - [Letter]. PMID- 26886693 TI - [Multimorbid patients - numerous illnesses, numerous therapies: a challenge due to interactions]. PMID- 26886695 TI - [Migraine - Principles and Treatment of a Widespread Disease]. AB - Headaches are amongst the most common reasons for visiting a general practitioner in Switzerland. The key features in differentiating migraine from other types of headache are the pulsating pain, interfering with daily activities, and the hypersensitivity to stimuli such as light or sound. Around 15 % of the patients report a preceeding aura, consisting of transient neurological symptoms. An effective migraine management is based on non-pharmacological treatment as well as acute and preventive medication. Non-pharmacological options include the management of the trigger factors stress, sleep deprivation, musculoskeletal tension. Acute treatment should be stratified and include non-opioid analgesics for milder attacks, triptans or combinations for more severe attacks. The spectrum of preventive medication is broad. Therefore it is essential to find a suitable and well tolerable drug for the individual patient. PMID- 26886696 TI - [Spirometry in the GP-Office]. AB - Spirometry is an important diagnostic tool, which, with correct implementation, detects possible obstructive or restrictive lung diseases. However, it is important to note that only part of the lung function is measured by spirometry. For instance, total lung volume and residual volume, both useful in detecting pulmonary emphysema, are not measured. Therefore, in case of pathological spirometry or suspected restrictive lung disease, further tests such as body plethysmography with diffusion measurement should be carried out. PMID- 26886697 TI - [Acute Chest Pain]. AB - Acute chest pain is a frequent consultation reason in general practice as well as in emergency departments. With the help of history, physical examination, ECG, laboratory and newly developed risk scores, potentially life-threatening diseases and high-risk patients may be detected and treated early, quickly and cost effectively. New biomarkers and their combination with risk scores can increase the negative predictive value to exclude certain diseases. PMID- 26886698 TI - [How Reliable is Neuronavigation?]. AB - Neuronavigation plays a central role in modern neurosurgery. It allows visualizing instruments and three-dimensional image data intraoperatively and supports spatial orientation. Thus it allows to reduce surgical risks and speed up complex surgical procedures. The growing availability and importance of neuronavigation makes clear how relevant it is to know about its reliability and accuracy. Different factors may influence the accuracy during the surgery unnoticed, misleading the surgeon. Besides the best possible optimization of the systems themselves, a good knowledge about its weaknesses is mandatory for every neurosurgeon. PMID- 26886699 TI - [Does long-term use of proton pump inhibitors promote premalignant lesions of the gastric mucosa?]. PMID- 26886700 TI - [Walking exercise for patients with peripheral arterial occlusive disease helps patients with and without revascularization]. PMID- 26886701 TI - [Intensive blood pressure treatment vs. less intensive treatment]. PMID- 26886703 TI - [Ultrasonography 68. Evaluation of fatigue]. PMID- 26886706 TI - Comparative Proteomics Provides Insights into Metabolic Responses in Rat Liver to Isolated Soy and Meat Proteins. AB - It has been reported that isolated dietary soy and meat proteins have distinct effects on physiology and liver gene expression, but the impact on protein expression responses are unknown. Because these may differ from gene expression responses, we investigated dietary protein-induced changes in liver proteome. Rats were fed for 1 week semisynthetic diets that differed only regarding protein source; casein (reference) was fully replaced by isolated soy, chicken, fish, or pork protein. Changes in liver proteome were measured by iTRAQ labeling and LC ESI-MS/MS. A robust set totaling 1437 unique proteins was identified and subjected to differential protein analysis and biological interpretation. Compared with casein, all other protein sources reduced the abundance of proteins involved in fatty acid metabolism and Pparalpha signaling pathway. All dietary proteins, except chicken, increased oxidoreductive transformation reactions but reduced energy and essential amino acid metabolic pathways. Only soy protein increased the metabolism of sulfur-containing and nonessential amino acids. Soy and fish proteins increased translation and mRNA processing, whereas only chicken protein increased TCA cycle but reduced immune responses. These findings were partially in line with previously reported transcriptome results. This study further shows the distinct effects of soy and meat proteins on liver metabolism in rats. PMID- 26886707 TI - Sex Ideologies in China: Examining Interprovince Differences. AB - In recent decades, premarital sex, extramarital sex, and homosexuality have become increasingly visible in China, leading scholars to claim that a national "sex revolution" is under way. However, China's internal sociocultural diversity calls this nation-level generalization into question. How do sex ideologies vary across China's distinct provinces? To what extent are interprovince variations in sex ideologies associated with distinct macrolevel social factors in China? In this research, data from the 2010 China General Social Survey and the 2011 Chinese Statistics Yearbook were analyzed using multilevel models to test four contending theories of interprovince differences in sex ideologies in China: modernization, Westernization, deindustrialization, and the "rice theory." The modernization theory was unsupported by the results, as socioeconomic development is not significantly associated with sex ideologies. Higher levels of deindustrialization and Westernization were associated with less traditional sex ideologies, but the strength of association varied across the domains of premarital sex, extramarital sex, and homosexuality. The rice theory was consistently supported, as the distinction between rice and wheat agriculture explained up to 30% of the province-level variance in sex ideologies. The findings underline the roles of both long-standing geographic differences and recent social changes in shaping China's ideational landscape of sex. PMID- 26886708 TI - [Paradoxical low-flow low-gradient aortic stenosis]. AB - In approximately one third of patients presenting with suspected severe aortic stenosis, there is a discrepancy between a severely reduced aortic valve opening area (< 1 cm(2)) and a non-severe increase of the mean transvalvular gradient (< 40 mmHg). In a substantial number of these cases there is evidence of a severe paradoxical low-flow low-gradient aortic stenosis, characterized by a reduced stroke volume index in the setting of a normal left ventricular ejection fraction. This finding should trigger an extensive diagnostic work-up, including echocardiography, stress echocardiography and computed tomography to rule out measurement errors and to identify the cause(s) of the hemodynamic discrepancy. If the diagnosis of a severe paradoxical low-flow low-gradient aortic stenosis is confirmed and, furthermore, the patient is normotensive and reports stenosis associated symptoms, the feasibility of an aortic valve replacement should be considered. PMID- 26886709 TI - [Pharmacotherapy of urinary incontinence in the elderly]. AB - The prevalence and the incidence of Urinary Incontinence is growing. Women suffer predominantly from stress and mixed urinary incontinence and men from urge incontinence. In elderly people, the pathophysiological and the physiological change in the lower urinary tract system must be considered as well as an underlying multimorbidity. Stress urinary incontinence is among others caused by an insufficient urethral closure mechanism and urge incontinence is followed by unhibited detrusor contractions. Medical treatment is beside other important conservative options only one part of the treatment strategy in incontinence. Duloxetine, a serotonine-norepinephrine reuptake inhibitore can increase activity of the external urethral sphincter and is able to reduce incontinence episodes in up to 64 %. Antagonists of muscarinic receptors can reduce urgency, frequency and urge incontinence as well as increase bladder capacity significantly. In Germany, darifenacin, fesoterodin, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride are available to treat urge incontinence. The efficacy of these agents are almost comparable in the elderly with the exception of oxybutynin IR. However, tolerability is different and not well studied in the elderly population with the exception of fesoterodin. Side effects, especially dry mouth, dizziness and constipation often limit their use. None of the agents show ideal efficacy or tolerability in all patients. Last summer therefore a beta3-agonist mirabegron was also introduced in Germany but was withdrawn. PMID- 26886712 TI - Friable Nodules on the Elbow of a Transplant Patient. PMID- 26886710 TI - [Current therapeutic strategies for mantle cell lymphoma]. AB - Mantle cell lymphoma is a subtype of B-cell lymphoma with a mostly aggressive behavior and poor long-term prognosis. The choice of therapy depends on the age, performance status and risk profile of the patient. Randomized trials have confirmed the superiority of a dose-intensified induction therapy containing cytarabine followed by autologous stem cell transplantation in the first-line treatment of younger patients with a good general condition. Elderly patients benefit from a rituximab maintenance therapy after immunochemotherapy. Novel targeted therapies of the B-cell receptor pathway with the Bruton's tyrosine kinase inhibitor ibrutinib and the mechanistic target of rapamycin (mTOR) antagonist temsirolimus as well as immunomodulatory drugs (lenalidomide) have shown promising results in relapsed disease. The proteasome inhibitor bortezomib has been approved for first-line treatment in combination with conventional chemotherapy. PMID- 26886711 TI - Chlamydomonas reinhardtii chloroplasts express an orally immunogenic protein targeting the p210 epitope implicated in atherosclerosis immunotherapies. AB - KEY MESSAGE: An algae-based vaccine model against atherosclerosis was developed with positive findings in terms of antigen yield and immunogenicity in mouse. Several immunotherapies against atherosclerosis have been evaluated at the preclinical level thus far, with some of them currently under evaluation in clinical trials. In particular, the p210 epitope from ApoB100 is known to elicit atheroprotective responses. Considering that Chlamydomonas reinhardtii is an attractive host for the production and delivery of subunit vaccines, in this study a chimeric protein consisting of the B subunit of the cholera toxin and the p210 epitope from ApoB100 (CTB:p210) has been expressed in C. reinhardtii chloroplast as an attempt to establish an oral vaccine candidate against atherosclerosis. The Chlamydomonas-made CTB:p210 protein was successfully expressed at levels of up to 60 ug per g of fresh weight biomass. The antigenic activity of the CTB and the p210 moiety was preserved in the CTB:p210 chimera. Moreover the algae-made CTB:p210 showed an immunogenic activity, when orally administered to BALB/c mice, as evidenced the presence of anti-p210 serum antibodies in mice treated with the algae-derived CTB:p210. The antibody response lasts for at least 80 days after the last boost. This experimental model is proposed as a convenient tool in the development of low cost atherosclerosis vaccines of easy compliance and friendly delivery. Further studies will determine the therapeutic potential of this algae-made vaccine in atherosclerosis animal models. PMID- 26886714 TI - Rituximab-refractory lupus nephritis successfully treated with belimumab. PMID- 26886713 TI - An Examination of Social Anxiety in Marijuana and Cigarette Use Motives Among Adolescents. AB - Marijuana and nicotine are two of the most widely used substances among adolescents in the United States. Symptoms of social anxiety (SA) typically emerge during early adolescence, and elevated levels are associated with increased substance-related problems despite inconsistent links to frequency of use. Substance use motives, and in particular coping motives, have been found to play an important role in understanding the heightened risk for use problems among those with elevated SA. Importantly, work to date has been conducted almost exclusively with adult samples; thus the current study examined whether similar patterns would emerge among adolescents. The current project included 56 community-recruited adolescents (ages 12-17 years; 41% girls) with a positive history of lifetime marijuana and cigarette use. Consistent with the adult literature, SA was not positively associated with frequency of use across either substance. Further, SA was positively associated with conformity use motives and unrelated to social or enhancement motives for both substances. Unexpectedly, SA was unrelated to coping use motives for either marijuana or cigarettes. These preliminary data highlight the need for future research designed to forward developmentally sensitive models of substance use behaviors and etiology. PMID- 26886715 TI - A Facile Method for in Situ Preparation of the MnO2/LaMnO3 Catalyst for the Removal of Toluene. AB - MOx/ABO3 is a promising catalyst for the high-efficiency removal of volatile organic compounds. However, this catalyst is limited on practical applications due to its complex synthesis procedure and high cost. In this work, the MnO2/LaMnO3 catalyst was prepared in situ using a facile one-step method for the first time, in which partial La cations were selectively removed from three dimensionally chain-like ordered macroporous (3DOM) LaMnO3 material. After selective removal, the obtained MnO2/LaMnO3 sample expressed an excellent catalytic performance on toluene oxidation. Toluene could be completely oxidized into CO2 and H2O at 290 degrees C over the MnO2/LaMnO3 catalyst with a toluene/oxygen molar ratio of 1/100 and a space velocity of 120 000 mL/(g h). In addition, the apparent activation energy value of MnO2/LaMnO3 was 57 kJ/mol, which was lower than those of other metal oxides catalysts. According to O2-TPD and XPS results, it is concluded that the high catalytic performance of MnO2/LaMnO3 was mainly associated with the large amount of oxygen species and the excellent lattice oxygen mobility. MnO2/LaMnO3 is a promising catalyst for the practical removal of volatile organic compounds due to its high efficiency, good stability, low cost, and convenient preparation. PMID- 26886717 TI - Ultrafast exciton-polariton scattering towards the Dirac points. AB - Using the Feynman-Dyson diagram technique, we study nonlinear polariton-polariton scattering in a two-dimensional micropillar-based optical superlattice with hexagonal symmetry. We demonstrate that both the emerging polariton chirality and the loop Feynman diagrams up to infinite order should be strictly accounted for in the evaluation of the self-energy of the system. Further, we explicitly show that in such a design the time of polariton scattering towards the Dirac points can be drastically decreased which can be used, for instance, in engineering novel classes of polariton lasers with substantially reduced thresholds. PMID- 26886716 TI - Vitamin E Improves Serum Paraoxonase-1 Activity and Some Metabolic Factors in Patients with Type 2 Diabetes: No Effects on Nitrite/Nitrate Levels. AB - OBJECTIVE: It is known that markers of oxidative stress and nitrite/nitrate anion (NOx) increase and activity of antioxidative enzyme paraoxonase-1 decline in type 2 diabetes mellitus (DM). The effects of vitamin E on paraoxonase-1 activity and NOx in patients with type 2 diabetes are not known. The purpose of this study was to examine the hypothesis that vitamin E supplementation would affect paraoxonase 1 activity, metabolic factors, and NOx in patients with DM. METHODS: This double blind, randomized, controlled clinical trial was conducted on 83 patients with DM aged 30-60 years. Forty-two of the subjects had taken 400 IU/day vitamin E and 41 were given placebo over 8 weeks. Fasting blood samples, anthropometric measurements, and dietary intake data were collected at the baseline and at the end of the trial. RESULTS: Vitamin E significantly increased serum vitamin E level, paraoxonase-1 activity, and total antioxidant status (TAS) and decreased fasting blood sugar (FBS) compared to the control group (p < 0.05). Hemoglobin A1c, serum insulin, and insulin resistance significantly decreased in the vitamin E group compared to baseline values (p < 0.05). Alterations in serum levels of malondialdehyde and NOx were not significant in any of groups (p > 0.05). CONCLUSIONS: Vitamin E improved serum vitamin E level, paraoxonase-1 activity, TAS, and FBS in patients with type 2 diabetes. Longitudinal studies are warranted to assess the outcome of these results in reducing complications of diabetes in patients with type 2 diabetes. PMID- 26886718 TI - Associations Between Parity, Obesity, and Cardiovascular Risk Factors Among Middle-Aged Women. AB - BACKGROUND: Several studies have demonstrated an association between parity and the risk of developing cardiovascular disease (CVD) in middle-aged women; however, some inconsistencies still remain in the literature after accounting for obesity. The purpose of this study was to examine the association between parity and the risk factors of CVD while accounting for current obesity status in middle aged women. METHOD: Data for this study came from the National Health and Nutrition Examination Survey 2007-2012. The final analytic sample included 2024 middle-aged women (40-60 years old). General linear models predicting CVD risk factors based on parity (nulliparous, 1, 2, 3, and >=4) were established after controlling for study covariates. Least square adjusted means of CVD risk factors and associated 95% confidence intervals were estimated across parity and body mass index (BMI) levels. RESULTS: Women with >=4 parity (8.34%; standard error [SE] = 0.84) showed significantly distinct demographic characteristics and health conditions, including obesity (49.08%; SE = 3.55). There were no significant associations between parity and CVD risk factors after controlling for covariates. Follow-up analyses showed consistent results across parity; however, CVD risk factors were significantly increased with higher BMI levels, regardless of parity status. CONCLUSIONS: Our results suggest that parity is not a significant predictor of CVD risk factors in middle-aged women, whereas current overweight or obesity status is more important when explaining the risk of the development of CVD. PMID- 26886719 TI - Thulium Laser Enucleation Versus Plasmakinetic Enucleation of the Prostate: A Randomized Trial of a Single Center. AB - PURPOSE: To compare the safety and efficacy of thulium laser enucleation of the prostate (ThuLEP) with plasmakinetic enucleation of the prostate (PKEP). METHODS: A total of 127 patients with benign prostatic hyperplasia (BPH) were randomized to either ThuLEP (n = 61) or PKEP (n = 66). All patients were assessed preoperatively and followed up at 3, 6, and 12 months postoperatively. Baseline characteristics of the patients, perioperative data, postoperative outcomes, and complications were recorded. RESULTS: The decrease in hemoglobin level and the catheter time were statistically significantly lower in the ThuLEP group compared with the PKEP group (0.80 +/- 0.49 vs 0.99 +/- 0.52, p = 0.037, and 1.85 +/- 0.94 vs 2.28 +/- 1.34, p = 0.042). There were no statistical differences in complications between the two groups (p > 0.05). There was a significant improvement in 3, 6, and 12 months' parameters compared with preoperative values (p < 0.001). Assessment at the 12-month follow-up showed no difference in urinary parameters between the two groups. CONCLUSIONS: ThuLEP and PKEP are both safe and efficient procedures for the treatment of patients with BPH. Compared with PKEP, ThuLEP provided less risk of hemorrhage and shorter catheter time, although the differences may be of little clinical relevance. Further well-designed trials with extended follow-up and larger sample size are needed to draw final conclusions about the efficacy of the two procedures. PMID- 26886720 TI - Use of Transnational Services to Prevent Treatment Interruption in Tuberculosis Infected Persons Who Leave the United States. AB - A major problem resulting from interrupted tuberculosis (TB) treatment is the development of drug-resistant TB, including multidrug-resistant TB (MDR TB), a more deadly and costly-to-treat form of the disease. Global health systems are not equipped to diagnose and treat the current burden of MDR TB. TB-infected foreign visitors and temporary US residents who leave the country during treatment can experience treatment interruption and, thus, are at greater risk for drug-resistant TB. Using epidemiologic and demographic data, we estimated TB incidence among this group, as well as the proportion of patients referred to transnational care-continuity and management services during relocation; each year, ~2,827 visitors and temporary residents are at risk for TB treatment interruption, 222 (8%) of whom are referred for transnational services. Scale up of transnational services for persons at high risk for treatment interruption is possible and encouraged because of potential health gains and reductions in healthcare costs for the United States and receiving countries. PMID- 26886721 TI - Tunable pH-Sensitive Linker for Controlled Release. AB - We have developed a novel pH-sensitive linker based on a phosphoramidate scaffold that can be tuned to release amine-containing drug molecules at various pH values. The pH-triggered phosphoramidate-based linkers are responsive to pH alone and do not require intracellular enzymatic action to initiate drug release. Key to the pH-triggered amine release from these linkers is a proximal acidic group (e.g., pyridinium or carboxylic acid) to promote the hydrolysis of the phosphoramidate P-N bond, presumably through an intramolecular general-acid type mechanism. Phosphoramidate hydrolysis is largely governed by the pKa of the leaving amine (e.g., primary, secondary, aniline). However, the proximity of the neighboring pyridine group attenuates the stability of the P-N bond to hydrolysis, thus allowing for control over the release of an amine from the phosphoramidate center. Based on the model scaffolds examined, phosphoramidate based linkers could be selected for particular properties for controlled-release applications such as amine type, stability under physiological conditions, or release rates at various pH values such as intracellular endosomal conditions. The tunability of the phosphoramidate scaffold is expected to find broad applicability in various controlled drug-release applications such as antibody or small-molecule drug conjugates, drug-eluting stents, prodrug activation, as well as intracellular trafficking studies in which pH changes can trigger the release of turn-on dyes. PMID- 26886722 TI - Treatment of Neuroleptic Malignant Syndrome with Electroconvulsive Therapy in an Adolescent with Psychosis. PMID- 26886724 TI - Role of Metabolic Activation in 8-Epidiosbulbin E Acetate-Induced Liver Injury: Mechanism of Action of the Hepatotoxic Furanoid. AB - 8-Epidiosbulbin E acetate (EEA), a furanoid, was unexpectedly found to be the most abundant diterpenoid lactone in certain varieties of Dioscorea bulbifera L. (DB), a traditional herbal medicine widely used in Asian nations. This herb has been reported to cause liver injury in humans and experimental animals. The occurrence of EEA in DB was dependent on its commercial source. The present study shows that EEA exhibits time- and dose-dependent liver injury in mice. Pretreatment with ketoconazole prevented the animals from developing EEA-induced liver injury, caused 7- and 13-fold increases in the plasma Cmax and AUC of EEA, and decreased urinary excretion of glutathione conjugates derived from EEA. Pretreatment with buthionine sulfoximine exacerbated EEA-induced hepatotoxicity. In order to define the role of EEA's furan moiety in EEA-induced hepatotoxicity, we synthesized tetrahydro-EEA by catalytic hydrogenation of the furan moiety. No liver injury was observed in the animals given the same doses of tetrahydro-EEA as those used with EAA. The results indicate that EEA itself does not appear to be hepatotoxic but that the electrophilic intermediate generated by the metabolic activation of the furan ring mediated by cytochromes P450 is responsible for EEA induced liver injury. PMID- 26886723 TI - 18alpha-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures. AB - AIMS: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. RESULTS: Feeding of wild-type Caenorhabditis elegans with 18alpha-glycyrrhetinic acid (18alpha-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Abeta deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18alpha-GA treatment. INNOVATION: This is the first report of the use of 18alpha-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. CONCLUSION: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855-869. PMID- 26886726 TI - White Polymer Light-Emitting Diodes Based on Exciplex Electroluminescence from Polymer Blends and a Single Polymer. AB - In this Article, we designed and synthesized a series of polyfluorene derivatives, which consist of the electron-rich 4,4'-(9-alkyl-carbazole-3,6 diyl)bis(N,N-diphenylaniline) (TPA-Cz) in the side chain and the electron deficient dibenzothiophene-5,5-dioxide (SO) unit in the main chain. The resulting copolymer PF-T25 that did not comprise the SO unit exhibited blue light-emission with the Commission Internationale de L'Eclairage coordinates of (0.16, 0.10). However, by physically blending PF-T25 with a blue light-emitting SO-based oligomer, a novel low-energy emission correlated to exciplex emerged due to the appropriate energy level alignment of TPA-Cz and the SO-based oligomers, which showed extended exciton lifetime as confirmed by time-resolved photoluminescent spectroscopy. The low-energy emission was also identified in copolymers consisting of SO unit in the main chain, which can effectively compensate for the high-energy emission to produce binary white light-emission. Polymer light emitting diodes based on the exciplex-type single greenish-white polymer exhibit the peak luminous efficiency of 2.34 cd A(-1) and the maximum brightness of 12 410 cd m(-2), with Commission Internationale de L'Eclairage color coordinates (0.27, 0.39). The device based on such polymer showed much better electroluminescent stability than those based on blending films. These observations indicated that developing a single polymer with the generated exciplex emission can be a novel and effective molecular design strategy toward highly stable and efficient white polymer light-emitting diodes. PMID- 26886725 TI - Effect of Imaging Parameter Thresholds on MRI Prediction of Neoadjuvant Chemotherapy Response in Breast Cancer Subtypes. AB - The purpose of this study is to evaluate the predictive performance of magnetic resonance imaging (MRI) markers in breast cancer patients by subtype. Sixty-four patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy were enrolled in this study. Each patient received a dynamic contrast-enhanced (DCE-MRI) at baseline, after 1 cycle of chemotherapy and before surgery. Functional tumor volume (FTV), the imaging marker measured by DCE-MRI, was computed at various thresholds of percent enhancement (PEt) and signal enhancement ratio (SERt). Final FTV before surgery and percent changes of FTVs at the early and final treatment time points were used to predict patients' recurrence-free survival. The full cohort and each subtype defined by the status of hormone receptor and human epidermal growth factor receptor 2 (HR+/HER2-, HER2+, triple negative) were analyzed. Predictions were evaluated using the Cox proportional hazard model when PEt changed from 30% to 200% in steps of 10% and SERt changed from 0 to 2 in steps of 0.2. Predictions with high hazard ratios and low p-values were considered as strong. Different profiles of FTV as predictors for recurrence-free survival were observed in each breast cancer subtype and strong associations with survival were observed at different PEt/SERt combinations that resulted in different FTVs. Findings from this retrospective study suggest that the predictive performance of imaging markers based on FTV may be improved with enhancement thresholds being optimized separately for clinically relevant subtypes defined by HR and HER2 receptor expression. PMID- 26886727 TI - New Transgenic Lines for Localization of GFP-Tagged Proteins by Electron Microscopy. PMID- 26886728 TI - Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis. AB - BACKGROUND: Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. METHODS: A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. RESULTS: Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. CONCLUSIONS: This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia. PMID- 26886730 TI - Open Access Meets Discoverability: Citations to Articles Posted to Academia.edu. AB - Using matching and regression analyses, we measure the difference in citations between articles posted to Academia.edu and other articles from similar journals, controlling for field, impact factor, and other variables. Based on a sample size of 31,216 papers, we find that a paper in a median impact factor journal uploaded to Academia.edu receives 16% more citations after one year than a similar article not available online, 51% more citations after three years, and 69% after five years. We also found that articles also posted to Academia.edu had 58% more citations than articles only posted to other online venues, such as personal and departmental home pages, after five years. PMID- 26886729 TI - Enhancing the Thermostability of Serratia plymuthica Sucrose Isomerase Using B Factor-Directed Mutagenesis. AB - The sucrose isomerase of Serratia plymuthica AS9 (AS9 PalI) was expressed in Escherichia coli BL21(DE3) and characterized. The half-life of AS9 PalI was 20 min at 45 degrees C, indicating that it was unstable. In order to improve its thermostability, six amino acid residues with higher B-factors were selected as targets for site-directed mutagenesis, and six mutants (E175N, K576D, K174D, G176D, S575D and N577K) were designed using the RosettaDesign server. The E175N and K576D mutants exhibited improved thermostability in preliminary experiments, so the double mutant E175N/K576D was constructed. These three mutants (E175N, K576D, E175N/K576D) were characterized in detail. The results indicate that the three mutants exhibit a slightly increased optimal temperature (35 degrees C), compared with that of the wild-type enzyme (30 degrees C). The mutants also share an identical pH optimum of 6.0, which is similar to that of the wild-type enzyme. The half-lives of the E175N, K576D and E175N/K576D mutants were 2.30, 1.78 and 7.65 times greater than that of the wild-type enzyme at 45 degrees C, respectively. Kinetic studies showed that the Km values for the E175N, K576D and E175N/K576D mutants decreased by 6.6%, 2.0% and 11.0%, respectively, and their kcat/Km values increased by 38.2%, 4.2% and 19.4%, respectively, compared with those of the wild-type enzyme. After optimizing the conditions for isomaltulose production at 45 degrees C, we found that the E175N, K576D and E175N/K576D mutants displayed slightly improved isomaltulose yields, compared with the wild type enzyme. Therefore, the mutants produced in this study would be more suitable for industrial biosynthesis of isomaltulose. PMID- 26886731 TI - GeneNetFinder2: Improved Inference of Dynamic Gene Regulatory Relations with Multiple Regulators. AB - A gene involved in complex regulatory interactions may have multiple regulators since gene expression in such interactions is often controlled by more than one gene. Another thing that makes gene regulatory interactions complicated is that regulatory interactions are not static, but change over time during the cell cycle. Most research so far has focused on identifying gene regulatory relations between individual genes in a particular stage of the cell cycle. In this study we developed a method for identifying dynamic gene regulations of several types from the time-series gene expression data. The method can find gene regulations with multiple regulators that work in combination or individually as well as those with single regulators. The method has been implemented as the second version of GeneNetFinder (hereafter called GeneNetFinder2) and tested on several gene expression datasets. Experimental results with gene expression data revealed the existence of genes that are not regulated by individual genes but rather by a combination of several genes. Such gene regulatory relations cannot be found by conventional methods. Our method finds such regulatory relations as well as those with multiple, independent regulators or single regulators, and represents gene regulatory relations as a dynamic network in which different gene regulatory relations are shown in different stages of the cell cycle. GeneNetFinder2 is available at http://bclab.inha.ac.kr/GeneNetFinder and will be useful for modeling dynamic gene regulations with multiple regulators. PMID- 26886732 TI - ChIP-PIT: Enhancing the Analysis of ChIP-Seq Data Using Convex-Relaxed Pair-Wise Interaction Tensor Decomposition. AB - In recent years, thanks to the efforts of individual scientists and research consortiums, a huge amount of chromatin immunoprecipitation followed by high throughput sequencing (ChIP-seq) experimental data have been accumulated. Instead of investigating them independently, several recent studies have convincingly demonstrated that a wealth of scientific insights can be gained by integrative analysis of these ChIP-seq data. However, when used for the purpose of integrative analysis, a serious drawback of current ChIP-seq technique is that it is still expensive and time-consuming to generate ChIP-seq datasets of high standard. Most researchers are therefore unable to obtain complete ChIP-seq data for several TFs in a wide variety of cell lines, which considerably limits the understanding of transcriptional regulation pattern. In this paper, we propose a novel method called ChIP-PIT to overcome the aforementioned limitation. In ChIP PIT, ChIP-seq data corresponding to a diverse collection of cell types, TFs and genes are fused together using the three-mode pair-wise interaction tensor (PIT) model, and the prediction of unperformed ChIP-seq experimental results is formulated as a tensor completion problem. Computationally, we propose efficient first-order method based on extensions of coordinate descent method to learn the optimal solution of ChIP-PIT, which makes it particularly suitable for the analysis of massive scale ChIP-seq data. Experimental evaluation the ENCODE data illustrate the usefulness of the proposed model. PMID- 26886733 TI - The Intrinsic Geometric Structure of Protein-Protein Interaction Networks for Protein Interaction Prediction. AB - Recent developments in high-throughput technologies for measuring protein-protein interaction (PPI) have profoundly advanced our ability to systematically infer protein function and regulation. However, inherently high false positive and false negative rates in measurement have posed great challenges in computational approaches for the prediction of PPI. A good PPI predictor should be 1) resistant to high rate of missing and spurious PPIs, and 2) robust against incompleteness of observed PPI networks. To predict PPI in a network, we developed an intrinsic geometry structure (IGS) for network, which exploits the intrinsic and hidden relationship among proteins in network through a heat diffusion process. In this process, all explicit PPIs participate simultaneously to glue local infinitesimal and noisy experimental interaction data to generate a global macroscopic descriptions about relationships among proteins. The revealed implicit relationship can be interpreted as the probability of two proteins interacting with each other. The revealed relationship is intrinsic and robust against individual, local and explicit protein interactions in the original network. We apply our approach to publicly available PPI network data for the evaluation of the performance of PPI prediction. Experimental results indicate that, under different levels of the missing and spurious PPIs, IGS is able to robustly exploit the intrinsic and hidden relationship for PPI prediction with a higher sensitivity and specificity compared to that of recently proposed methods. PMID- 26886734 TI - A Novel Teaching-Learning-Based Optimization for Improved Mutagenic Primer Design in Mismatch PCR-RFLP SNP Genotyping. AB - Many single nucleotide polymorphisms (SNPs) for complex genetic diseases are genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in small-scale basic research studies. It is an essential work to design feasible PCR-RFLP primer pair and find out available restriction enzymes to recognize the target SNP for PCR experiments. However, many SNPs are incapable of performing PCR-RFLP makes SNP genotyping become unpractical. A genetic algorithm (GA) had been proposed for designing mutagenic primer and get available restriction enzymes, but it gives an unrefined solution in mutagenic primers. In order to improve the mutagenic primer design, we propose TLBOMPD (TLBO-based Mutagenic Primer Design) a novel computational intelligence-based method that uses the notion of "teaching and learning" to search for more feasible mutagenic primers and provide the latest available restriction enzymes. The original Wallace's formula for the calculation of melting temperature is maintained, and more accurate calculation formulas of GC-based melting temperature and thermodynamic melting temperature are introduced into the proposed method. Mutagenic matrix is also reserved to increase the efficiency of judging a hypothetical mutagenic primer if involve available restriction enzymes for recognizing the target SNP. Furthermore, the core of SNP-RFLPing version 2 is used to enhance the mining work for restriction enzymes based on the latest REBASE. Twenty-five SNPs with mismatch PCR-RFLP screened from 288 SNPs in human SLC6A4 gene are used to appraise the TLBOMPD. Also, the computational results are compared with those of the GAMPD. In the future, the usage of the mutagenic primers in the wet lab needs to been validated carefully to increase the reliability of the method. The TLBOMPD is implemented in JAVA and it is freely available at http://tlbompd.googlecode.com/. PMID- 26886735 TI - Discovering Motifs in Biological Sequences Using the Micron Automata Processor. AB - Finding approximately conserved sequences, called motifs, across multiple DNA or protein sequences is an important problem in computational biology. In this paper, we consider the (l, d) motif search problem of identifying one or more motifs of length l present in at least q of the n given sequences, with each occurrence differing from the motif in at most d substitutions. The problem is known to be NP-complete, and the largest solved instance reported to date is (26,11). We propose a novel algorithm for the (l,d) motif search problem using streaming execution over a large set of non-deterministic finite automata (NFA). This solution is designed to take advantage of the micron automata processor, a new technology close to deployment that can simultaneously execute multiple NFA in parallel. We demonstrate the capability for solving much larger instances of the (l, d) motif search problem using the resources available within a single automata processor board, by estimating run-times for problem instances (39,18) and (40,17). The paper serves as a useful guide to solving problems using this new accelerator technology. PMID- 26886736 TI - Fractal Behavior of the Pancreatic beta-Cell Near the Percolation Threshold: Effect of the KATP Channel On the Electrical Response. AB - The molecular system built with true chemical bonds or strong molecular interaction can be described using conceptual mathematical tools. Modeling of the natural generated ionic currents on the human pancreatic beta-cell activity had been already studied using complicated analytical models. In our present contribution, we prove the same using our simple electrical model. The ionic currents are associated with different proteins membrane channels (K-Ca, K(v), K(ATP), Ca(v)-L) and Na/Ca Exchanger (NCX). The proteins are Ohmic conductors and are modeled by conductance randomly distributed. Switches are placed in series with conductances in order to highlight the channel activity. However, the KATP channel activity is stimulated by glucose, and the NCX's conductance change according to the intracellular calcium concentration. The percolation threshold of the system is calculated by the fractal nature of the infinite cluster using the Tarjan's depth-first-search algorithm. It is shown that the behavior of the internal concentration of Ca(2+) and the membrane potential are modulated by glucose. The results confirm that the inhibition of KATP channels depolarizes the membrane and increases the influx of [Ca(2+)]i through NCX and Ca(v)-L channel for high glucose concentrations. PMID- 26886737 TI - gEFM: An Algorithm for Computing Elementary Flux Modes Using Graph Traversal. AB - Computational methods to engineer cellular metabolism promise to play a critical role in producing pharmaceutical, repairing defective genes, destroying cancer cells, and generating biofuels. Elementary Flux Mode (EFM) analysis is one such powerful technique that has elucidated cell growth and regulation, predicted product yield, and analyzed network robustness. EFM analysis, however, is a computationally daunting task because it requires the enumeration of all independent and stoichiometrically balanced pathways within a cellular network. We present in this paper an EFM enumeration algorithm, termed graphical EFM or gEFM. The algorithm is based on graph traversal, an approach previously assumed unsuitable for enumerating EFMs. The approach is derived from a pathway synthesis method proposed by Mavrovouniotis et al. The algorithm is described and proved correct. We apply gEFM to several networks and report runtimes in comparison with other EFM computation tools. We show how gEFM benefits from network compression. Like other EFM computational techniques, gEFM is sensitive to constraint ordering; however, we are able to demonstrate that knowledge of the underlying network structure leads to better constraint ordering. gEFM is shown to be competitive with state-of-the-art EFM computational techniques for several networks, but less so for networks with a larger number of EFMs. PMID- 26886738 TI - Globally Asymptotic Stability Analysis for Genetic Regulatory Networks with Mixed Delays: An M-Matrix-Based Approach. AB - This paper deals with the problem of globally asymptotic stability for nonnegative equilibrium points of genetic regulatory networks (GRNs) with mixed delays (i.e., time-varying discrete delays and constant distributed delays). Up to now, all existing stability criteria for equilibrium points of the kind of considered GRNs are in the form of the linear matrix inequalities (LMIs). In this paper, the Brouwer's fixed point theorem is employed to obtain sufficient conditions such that the kind of GRNs under consideration here has at least one nonnegative equilibrium point. Then, by using the nonsingular M-matrix theory and the functional differential equation theory, M-matrix-based sufficient conditions are proposed to guarantee that the kind of GRNs under consideration here has a unique nonnegative equilibrium point which is globally asymptotically stable. The M-matrix-based sufficient conditions derived here are to check whether a constant matrix is a nonsingular M-matrix, which can be easily verified, as there are many equivalent statements on the nonsingular M-matrices. So, in terms of computational complexity, the M-matrix-based stability criteria established in this paper are superior to the LMI-based ones in literature. To illustrate the effectiveness of the approach proposed in this paper, several numerical examples and their simulations are given. PMID- 26886739 TI - Identification of Glucose-Binding Pockets in Human Serum Albumin Using Support Vector Machine and Molecular Dynamics Simulations. AB - Human Serum Albumin (HSA) has been suggested to be an alternate biomarker to the existing Hemoglobin-A1c (HbA1c) marker for glycemic monitoring. Development and usage of HSA as an alternate biomarker requires the identification of glycation sites, or equivalently, glucose-binding pockets. In this work, we combine molecular dynamics simulations of HSA and the state-of-art machine learning method Support Vector Machine (SVM) to predict glucose-binding pockets in HSA. SVM uses the three dimensional arrangement of atoms and their chemical properties to predict glucose-binding ability of a pocket. Feature selection reveals that the arrangement of atoms and their chemical properties within the first 4A from the centroid of the pocket play an important role in the binding of glucose. With a 10-fold cross validation accuracy of 84 percent, our SVM model reveals seven new potential glucose-binding sites in HSA of which two are exposed only during the dynamics of HSA. The predictions are further corroborated using docking studies. These findings can complement studies directed towards the development of HSA as an alternate biomarker for glycemic monitoring. PMID- 26886740 TI - Relational Agreement Measures for Similarity Searching of Cheminformatic Data Sets. AB - Research on similarity searching of cheminformatic data sets has been focused on similarity measures using fingerprints. However, nominal scales are the least informative of all metric scales, increasing the tied similarity scores, and decreasing the effectivity of the retrieval engines. Tanimoto's coefficient has been claimed to be the most prominent measure for this task. Nevertheless, this field is far from being exhausted since the computer science no free lunch theorem predicts that "no similarity measure has overall superiority over the population of data sets". We introduce 12 relational agreement (RA) coefficients for seven metric scales, which are integrated within a group fusion-based similarity searching algorithm. These similarity measures are compared to a reference panel of 21 proximity quantifiers over 17 benchmark data sets (MUV), by using informative descriptors, a feature selection stage, a suitable performance metric, and powerful comparison tests. In this stage, RA coefficients perform favourably with repect to the state-of-the-art proximity measures. Afterward, the RA-based method outperform another four nearest neighbor searching algorithms over the same data domains. In a third validation stage, RA measures are successfully applied to the virtual screening of the NCI data set. Finally, we discuss a possible molecular interpretation for these similarity variants. PMID- 26886741 TI - TIRF high-content assay development for the evaluation of drug efficacy of chemotherapeutic agents against EGFR-/HER2-positive breast cancer cell lines. AB - Elevated expression of epidermal growth factor receptor (EGFR) is reported to be associated with poor prognosis in breast cancer. EGFR subtype identification plays a crucial role in deciding the drug combination to treat the cancer patients. Conventional application of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) produces more discordance results in EGFR subtype identification of cancer specimens. The present study is designed to develop an analytical method for simultaneous identification of cell surface biomarkers and quantitative estimation of drug efficacy in cancer specimens. For this study, we have utilized a total internal reflection fluorescence microscope (TIRFM), Qdot molecular probes and chemotherapeutic agent camptothecin (CPT)-treated breast cancer cell lines namely MCF-7, SK-BR-3 and JIMT-1. Highly sensitive detection signals with low background noise generated from the evanescent field excitation of TIRFM make it a highly suitable tool to detect the cell surface biomarkers in living cells. Moreover, single wavelength excitation of Qdot probes offers multicolour imaging with strong emission brightness. In the present study, TIRF high-content imaging system simultaneously showed the expression pattern of EGFRs and EC50 value for CPT-induced apoptosis and necrosis in MCF-7, SK-BR-3 and JIMT 1 cancer cell lines. PMID- 26886742 TI - A comparative study of phosphopeptide-selective techniques for a sub-proteome of a complex biological sample. AB - Phosphorylation of proteins is important for controlling cellular signaling and cell cycle regulatory events. The process is reversible and phosphoproteins normally constitute a minor part of the global proteome in a cell. Thus, sample preparation techniques tailored for phosphoproteome studies are continuously invented and evaluated. This paper aims at evaluating the performances of the most popular techniques for phospho-enrichments in sub-proteome analysis, such as viral proteomes expressed in human cells during infection. A two-species sample of Adenovirus type 2 infected human cells was used, and in-solution digestion, strong cation exchange (SCX), and electrostatic repulsion hydrophilic interaction chromatography (ERLIC) fractionation, and subsequent enrichment by TiO2, were compared with SDS-PAGE fractionation and in-gel digestion. Evaluation was focused on phosphopeptide detection in the sub-proteome. The results showed that the SCX+TiO2 or ERLIC+TiO2 combinations had the highest enrichment efficiencies, but SDS-PAGE fractionation and in-gel digestion resulted in the highest number of identified proteins and phosphopeptides. Furthermore, the study demonstrates the usefulness of applying as many orthogonal techniques as possible in deep phosphoproteome analysis, since the overlap between approaches was low. PMID- 26886744 TI - Merits of online electrochemistry liquid sample desorption electrospray ionization mass spectrometry (EC/LS DESI MS). AB - A new online electrochemistry/liquid sample desorption electrospray ionization mass spectrometry (EC/LS DESI MS) system with a simple electrochemical thin-layer flow-through cell was developed and tested using N,N-dimethyl-p-phenylenediamine (DMPA) as a model probe. Although oxidation of DMPA is observed as a result of ionization of LS in positive ion mode LS DESI, application of voltage to the online electrochemical (EC) cell in EC/LS DESI MS increases yields of oxidation products. An advantage of LS DESI MS is its sensitivity in aqueous electrolyte solutions, which improves efficiency of electrochemical reactions in EC/LS DESI MS. In highly conductive low pH aqueous buffer solutions, oxidation efficiency is close to 100%. EC/ESI MS typically requires mixed aqueous/organic solvents and low electrolyte concentrations for efficient ionization in MS, limiting efficiency of electrochemistry online with MS. Independently, the results verify higher electrochemical oxidation efficiency during positive mode ESI than during LS DESI. PMID- 26886743 TI - Data independent acquisition-digital archiving mass spectrometry: application to single kernel mycotoxin analysis of Fusarium graminearum infected maize. AB - New and conjugated mycotoxins of concern to regulators are frequently being identified, necessitating the costly need for new method development and sample reanalysis. In response, we developed an LC-data independent acquisition (LC-DIA) method on a Q-Exactive Orbitrap mass spectrometer tailored for mycotoxins analysis. This method combines absolute quantification of targeted fungal metabolites with non-targeted digital archiving (DA) of data on all ionizable compounds for retrospective analysis. The quantitative power of this approach was assessed by spiking 23 mycotoxins at a range of concentrations into clean maize extracts. The linearity and limits of detection achieved were comparable to conventional LC-MS/MS and significantly better than 'all-ion-fragmentation' scanning mode. This method was applied to single kernel analysis of Fusarium infected maize, where we quantified nine Fusarium metabolites and three metabolites from unexpected contaminations by Alternaria and Penicillium species. Retrospective analysis of this data set allowed us to detect the recently reported 15-acetyldeoxynivalenol-3-O-beta-D-glucoside without requiring re analysis of the samples. To our knowledge, this is the first reported occurrence of this conjugated mycotoxin in naturally contaminated maize, and led us to further study maize artificially inoculated with the 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol chemotypes of Fusarium graminearum. Analysis of these samples showed that the maize genotype tested glycosylates 15 acetyldeoxynivalenol but not 3-acetyldeoxynivalenol likely because the glycosylation site was blocked. In addition to confirming that these two F. graminearum chemotypes behave differently when infecting the host plant, it demonstrates the utility of using a single screening method to quantify known mycotoxins and archive a completely non-targeted dataset for future analysis. PMID- 26886745 TI - State of the art in the determination of trace elements in seawater: a worldwide proficiency test. AB - This manuscript presents the results of the International Measurement Evaluation Programme 40 (IMEP-40) study, a proficiency test (PT) which was organised to assess the worldwide performance of laboratories for the determination of trace elements in seawater. This PT supports the implementation of the European Union Water Framework Directive 2000/60/EC, which aims at achieving a long-term high level protection of the aquatic environment, covering lakes, ground water and coastal waters. Forty-six participants reported results. The test item was seawater containing the trace elements As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se and Zn. The trace elements in the test item were present in very low concentrations to mimic natural levels. The results of the participants were rated with z and zeta (zeta) scores in accordance with ISO 13528 and ISO 17043. The standard deviation for proficiency assessment, sigma, was set at 25% of the respective assigned values for the 12 measured elements based on previous experience with similar PTs. The low levels of the trace elements combined with the high salt concentration of the seawater made the measurements challenging. Many laboratories were unable to detect or quantify the elements and reported "lower than X" values. The percentage of satisfactory performances (expressed as z scores) ranged from 41% (Cr, Fe) to 86% (Mo). The PT study showed that the use of proper standard methods, like ISO 17294-2, and sensitive techniques, like inductively coupled plasma mass spectrometry (ICP-MS), contributed to performing well in this PT round. PMID- 26886746 TI - Effects of Electroconvulsive Therapy on Some Inflammatory Factors in Patients With Treatment-Resistant Schizophrenia. AB - OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective option for several psychiatric conditions, including treatment-resistant schizophrenia. However, little is known about the molecular mechanism of action of ECT. The link between inflammatory system and schizophrenia is the focus of recent studies. However, the impact of ECT on inflammatory functioning in this disorder remains elusive. Whether ECT could modulate inflammatory factors in patients with schizophrenia was examined. METHODS: Plasma levels of interleukin-4 (IL-4), transforming growth factor-beta (TGF-beta), myeloperoxidase (MPO), and nuclear factor-kappaB (NF-kappaB) activation were analyzed in 20 schizophrenic patients, mainly with resistant to antipsychotic medication disorders, and in 20 sex- and age-matched healthy controls. Disease severity was evaluated using the Brief Psychiatric Rating Scale. All patients were followed with measurement of the inflammatory factors before and after ECT treatment and compared with the controls. RESULTS: Patients with schizophrenia had markedly raised NF-kappaB and but decreased TGF-beta levels compared with healthy controls. On the other hand, no significant differences were found for the levels of IL-4 and MPO levels. The clinical improvement during repeated ECT was accompanied by a gradual and significant increase in IL-4 and TGF-beta level, but MPO and NF-kappaB activation were left unaffected. Increases in TGF-beta were negatively correlated with the change in Brief Psychiatric Rating Scale scores after ECT. CONCLUSIONS: It is shown that ECT, while increasing the anti-inflammatory response such as the levels of IL-4 and TGF-beta, it did not affect the levels of MPO and NF-kappaB activation in this study. PMID- 26886747 TI - Fused Catechol Ethers from Gold(I)-Catalyzed Intramolecular Reaction of Propargyl Ethers with Acetals. AB - Selective gold(I)-catalyzed rearrangement of aromatic methoxypropynyl acetals leads to fused catechol ethers (1,2-dialkoxynapthalenes) in excellent yields. Furthermore, this process extends to the analogous heterocyclic and aliphatic substrates. Alkyne activation triggers nucleophilic addition of the acetal oxygen that leads to an equilibrating mixture of oxonium ions of similar stability. This mixture is "kinetically self-sorted" via a highly exothermic cyclization. Selective formation of 1,2-dialkoxy naphthalenes originates from chemoselective aromatization of the cyclic intermediate via 1,4-elimination of methanol. PMID- 26886748 TI - Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family. AB - Recently, the epidermal growth factor (EGF) receptor (EGFR), a member of the ErbB receptor family, and its down-stream signalling have been identified as co factors for HCV entry and replication. Since EGFR also functions as a heterodimer with other ErbB receptor family members, the subject of the present study was to investigate a possible viral interference with these cellular components. By using genotype 1b replicon cells as well as an infection-based system we found that while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, HCV induced a substantial reduction of ErbB3 and ErbB4 expression. Down-regulation of ErbB3 expression by HCV involves specificity protein (Sp)1-mediated induction of Neuregulin (NRG)1 expression as well as activation of Akt. Consistently, at transcript level disruption of ErbB3 expression by HCV can be prevented by knockdown of NRG1 or Sp1 expression, whereas reconstitution of ErbB3 protein levels requires inhibition of HCV-induced NRG1 expression and of Akt activity. Interestingly, the NRG1-mediated suppression of ErbB3 expression by HCV results in an enhanced expression of EGFR and ErbB2 on the cell surface, which can be mimicked by siRNA-mediated knockdown of ErbB3 expression. These data delineate a novel mechanism enabling HCV to sway the composition of the ErbB family members on the surface of its host cell by an NRG1 driven circuit and unravels a yet unknown cross-regulation between ErbB3 and the two other family members ErbB2 and EGFR. The shift of the receptor surface expression of the ErbB family towards enhanced expression of ErbB2 and EGFR triggered by HCV was found to promote viral RNA replication and infectivity. This suggests that HCV rearranges expression of ErbB family members to adapt the cellular environment to its requirements. PMID- 26886749 TI - The Emergence and Spread of Multiple Livestock-Associated Clonal Complex 398 Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Strains among Animals and Humans in the Republic of Ireland, 2010-2014. AB - Clonal complex (CC) 398 methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) are associated with carriage and infection among animals and humans but only a single case of CC398 MRSA has been reported in the Republic of Ireland (ROI). The present study investigated the molecular epidemiology of CC398 MRSA (n = 22) and MSSA (n = 10) from animals and humans in the ROI from 2010-2014. Isolates underwent antimicrobial susceptibility testing, spa typing, DNA microarray profiling and PCR for CC398-associated resistance genes. All MRSA underwent SCCmec IV or V subtyping. Four distinct CC398-MRSA incidents were identified from (i) a man in a nursing home (spa type t011-SCCmec IVa, immune evasion complex (IEC) negative), (ii) a horse and veterinarian who had recently travelled to Belgium (t011-IVa, IEC positive), (iii) pigs (n = 9) and farm workers (n = 9) on two farms, one which had been restocked with German gilts and the other which was a finisher farm (t034-VT, IEC negative, 3/9 pigs; t011-VT, IEC negative, 6/9 pigs & 9/9 farm workers), and (iv) a child who had worked on a pig farm in the UK (t034-VT, IEC negative). Isolates also carried different combinations of multiple resistance genes including erm(A), erm(B), tet(K), tet(M) & tet(L), fexA, spc, dfrG, dfrK aacA-aphD and aadD further highlighting the presence of multiple CC398-MRSA strains. CC398 MSSA were recovered from pigs (n = 8) and humans (n = 2). CC398 MSSA transmission was identified among pigs but zoonotic transmission was not detected with animal and human isolates exhibiting clade-specific traits. This study highlights the importation and zoonotic spread of CC398 MRSA in the ROI and the spread of CC398 MSSA among pigs. Increased surveillance is warranted to prevent further CC398 MRSA importation and spread in a country that was considered CC398 MRSA free. PMID- 26886750 TI - Shengmai Formula Ameliorates Pathological Characteristics in AD C. elegans. AB - Shengmai (SM) formula, a classical traditional Chinese medicine formula, is composed of Panax ginseng (Pg), Ophiopogon japonicus (Oj), and Schisandra Chinesis (Sc). SM has been clinically used to treat heart failure and ischemic heart disease. Although SM formula has been reported to be potential for fighting against Alzheimer's disease (AD) by previous works, there are many gaps in our knowledge on its usage in AD treatment on an organism level and will then need to be further clarified. In this study, transgenic Caenorhabditis elegans expressing human Abeta1-42 are used to evaluate SM formula efficacy to treat AD phenotype and to investigate its underlying mechanism. The results showed that SM formula ameliorated AD pathological characteristics of paralysis behavior and chemotaxis defect in transgenic C. elegans. With SM treatment, the number of Abeta deposits decreased, the levels of gene expressions of hsp16-2, hsp16-41, ace-1, ace-2, and TNFA1P1 homolog genes were down-regulated. Our results also showed that Oj exhibited more stronger effect on delaying paralysis in worms than Pg and Sc did, and synergistic action was observed between Pg and Oj, and Sc further enhanced the activity of Pg/Oj combination on delaying paralysis behavior. Further, SM with herbs of Pg, Oj, and Sc at a dose proportion of 9:9:6 exhibited superior therapeutic efficacy in comparison with herbs at other dose proportions. After SM formula extracted by ethanol, it delayed AD symptoms on a wider dose from 0.2 to 10.0 mg/mL with no toxic effect. These results provided more evidence for SM formula being potential to be used to treat AD. PMID- 26886751 TI - Stichopus japonicus Polysaccharide, Fucoidan, or Heparin Enhanced the SDF 1alpha/CXCR4 Axis and Promoted NSC Migration via Activation of the PI3K/Akt/FOXO3a Signaling Pathway. AB - Stichopus japonicus Polysaccharide (SJP) is a sulfated polysaccharide from the body wall of the sea cucumber, Stichopus japonicus. Fucoidan is a heparinoid compound that belongs to a family of sulfated polyfucose polysaccharides. Heparin is a glycosaminoglycan. SJP, fucoidan, and heparin profoundly promoted stromal cell-derived factor 1 alpha (SDF-1alpha)-induced neural stem cell (NSC) migration in a concentration-dependent manner. In addition, the basal migration capacity of cells was significantly promoted after incubation with SJP, fucoidan, or heparin. Interaction of SJP, fucoidan, or heparin with SDF-1alpha efficiently showed additive effects on the promotion of cell migration from the neurosphere. SJP, fucoidan, or heparin interaction with SDF-1alpha treatment could increase Nestin expression. SDF-1alpha modulated by SJP, fucoidan, or heparin activated the CXCR4 receptor and directed cellular migration via the activation of the PI3K/Akt/FOXO3a signaling pathway. Moreover, interaction of SJP, fucoidan, or heparin with SDF-1alpha effectively promoted NSC migration and induced SDF-1alpha and CXCR4 expressions. Results suggested that SJP, fucoidan, and heparin might be good candidates for alleviating injury-initiated signals to which NSCs respond. PMID- 26886752 TI - Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation. AB - Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade. PMID- 26886753 TI - Dynamic Gradient of Glutamate Across the Membrane: Glutamate/Aspartate-Induced Changes in the Ambient Level of L-[14C]glutamate and D-[3H]aspartate in Rat Brain Nerve Terminals. AB - Extracellular/intracellular L-[14C]glutamate exchange and conservativeness of the extracellular level of L-[14C]glutamate was analyzed in isolated rat brain nerve terminals. L-Glutamate-, DL-threo-beta-hydroxyaspartate (DL-THA)-, and D aspartate-induced increase in the ambient level of L-[14C]glutamate or D [3H]aspartate was evaluated comparatively. 100 MUM "cold" nonradiolabeled L glutamate, DL-THA, D-aspartate extruded a quarter of radioactivity from L [14C]glutamate-preloaded synaptosomes for 6 min. The similar results were obtained with L-glutamate-evoked extracellular/intracellular redistribution of D [3H]aspartate. Contribution of presynaptic glutamate receptors to an increase in the extracellular L-[14C]glutamate level was evaluated using receptor agonists NMDA, AMPA, and kainate (100 MUM), and it consisted of less than 5 % of total accumulated label. The existence of the efficient extracellular/intracellular glutamate exchange, and so dynamic glutamate gradient across the plasma membrane of nerve terminals was demonstrated. A two-substrate kinetic algorithm that included transporter reversal was considered. The extracellular level of L [14C]glutamate and D-[3H]aspartate in nerve terminals depended on the amount of exogenous substrates of glutamate transporter available. Taking into account that L-glutamate, DL-THA, and D-aspartate are the substrates of glutamate transporters, and also the similarity in their effectiveness in the establishment of new extracellular level of the neurotransmitters, the central role of glutamate transporters in permanent glutamate turnover in nerve terminals was demonstrated. PMID- 26886754 TI - Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque. AB - Carotid atherosclerosis (AS) is a chronic inflammatory disease of the carotid arterial wall, which is very important in terms of the occurrence of cerebral vascular accidents. Studies have demonstrated that microRNAs (miRNAs) and their target genes are involved in the formation of atherosclerosis and that atorvastatin might reduce atherosclerotic plaques by regulating the expression of miRNAs. However, the related mechanism is not yet known. In this study, we first investigated the effects of atorvastatin on miR-126 and its target gene, i.e., vascular cell adhesion molecule-1 (VCAM-1) in apolipoprotein E-knockout (ApoE-/-) mice with carotid atherosclerotic plaque in vivo. We compared the expressions of miR-126 and VCAM-1 between the control, atherosclerotic model and atorvastatin treatment groups of ApoE-/- mice using RT-PCR and Western blot. We found the miR 126 expression was significantly down-regulated, and the VCAM-1 expression was significantly up-regulated in the atherosclerotic model group, which accelerated the progression of atherosclerosis in the ApoE-/- mice. These results following atorvastatin treatment indicated that miR-126 expression was significantly up regulated, VCAM-1 expression was significantly down-regulated and atherosclerotic lesions were reduced. The present results might explain the mechanism by which miR-126 is involved in the formation of atherosclerosis in vivo. Our study first indicated that atorvastatin might exert its anti-inflammatory effects in atherosclerosis by regulating the expressions of miR-126 and VCAM-1 in vivo. PMID- 26886755 TI - Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury. AB - Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID- 26886756 TI - Metabolic engineering of Rhodopseudomonas palustris for squalene production. AB - Squalene is a strong antioxidant used extensively in the food, cosmetic and medicine industries. Rhodopseudomonas palustris TIE-1 was used as the host because of its ability to grow photosynthetically using solar energy and carbon dioxide from atmosphere. The deletion of the shc gene resulted in a squalene production of 3.8 mg/g DCW, which was 27-times higher than that in the wild type strain. For constructing a substrate channel to elevate the conversion efficiency, we tried to fuse crtE gene with hpnD gene. By fusing the two genes, squalene content was increased to 12.6 mg/g DCW, which was 27.4 % higher than that resulted from the co-expression method. At last, the titer of squalene reached 15.8 mg/g DCW by co-expressing the dxs gene, corresponding to 112-fold increase relative to that for wild-type strain. This study provided novel strategies for improving squalene yield and demonstrated the potential of producing squalene by Rhodopseudomonas palustris. PMID- 26886757 TI - A mutant form of 3-ketosteroid-Delta(1)-dehydrogenase gives altered androst-1,4 diene-3, 17-dione/androst-4-ene-3,17-dione molar ratios in steroid biotransformations by Mycobacterium neoaurum ST-095. AB - Mycobacterium neoaurum ST-095 and its mutant M. neoaurum JC-12, capable of transforming phytosterol to androst-1,4-diene-3,17-dione (ADD) and androst-4-ene 3,17-dione (AD), produce very different molar ratios of ADD/AD. The distinct differences were related to the enzyme activity of 3-ketosteroid-Delta(1) dehydrogenase (KSDD), which catalyzes the C1,2 dehydrogenation of AD to ADD specifically. In this study, by analyzing the primary structure of KSDDI (from M. neoaurum ST-095) and KSDDII (from M. neoaurum JC-12), we found the only difference between KSDDI and KSDDII was the mutation of Val(366) to Ser(366). This mutation directly affected KSDD enzyme activity, and this result was confirmed by heterologous expression of these two enzymes in Bacillus subtilis. Assay of the purified recombinant enzymes showed that KSDDII has a higher C1,2 dehydrogenation activity than KSDDI. The functional difference between KSDDI and KSDDII in phytosterol biotransformation was revealed by gene disruption and complementation. Phytosterol transformation results demonstrated that ksdd I and ksdd II gene disrupted strains showed similar ADD/AD molar ratios, while the ADD/AD molar ratios of the ksdd I and ksdd II complemented strains were restored to their original levels. These results proved that the different ADD/AD molar ratios of these two M. neoaurum strains were due to the differences in KSDD. Finally, KSDD structure analysis revealed that the Val(366)Ser mutation could possibly play an important role in stabilizing the active center and enhancing the interaction of AD and KSDD. This study provides a reliable theoretical basis for understanding the structure and catalytic mechanism of the Mycobacteria KSDD enzyme. PMID- 26886758 TI - Immobilization of nitrilase on bioinspired silica for efficient synthesis of 2 hydroxy-4-(methylthio) butanoic acid from 2-hydroxy-4-(methylthio) butanenitrile. AB - In this paper, a simple and effective method using sodium metasilicate as precursor and amine as additive was first reported to immobilize recombinant nitrilase, for efficient production of 2-hydroxy-4-(methylthio) butanoic acid from 2-hydroxy-4-(methylthio) butanenitrile. High immobilization recovery of enzyme activity (above 90 %) was achieved. The immobilized enzyme displayed better thermal stability, pH stability and shelf life compared to free nitrilase. Moreover, it showed excellent reusability and could be recycled up to 16 batches without significant loss in activity. 200 mM 2-hydroxy-4-(methylthio) butanenitrile was completely converted by the immobilized enzyme within 30 min, and the accumulation amount of 2-hydroxy-4-(methylthio) butanoic acid reached 130 mmol/g of immobilized beads after 16 batches. These encouraging results demonstrated the efficiency of the new technology for nitrilase immobilization, which has great potential in preparation of 2-hydroxy-4-(methylthio) butanoic acid. PMID- 26886759 TI - Slippery slope arguments imply opposition to change. AB - Slippery slope arguments (SSAs) of the form if A, then C describe an initial proposal (A) and a predicted, undesirable consequence of this proposal (C) (e.g., "If cannabis is ever legalized, then eventually cocaine will be legalized, too"). Despite SSAs being a common rhetorical device, there has been surprisingly little empirical research into their subjective evaluation and perception. Here, we present evidence that SSAs are interpreted as a form of consequentialist argument, inviting inferences about the speaker's (or writer's) attitudes. Study 1 confirmed the common intuition that a SSA is perceived to be an argument against the initial proposal (A), whereas Study 2 showed that the subjective strength of this inference relates to the subjective undesirability of the predicted consequences (C). Because arguments are rarely made out of context, in Studies 3 and 4 we examined how one important contextual factor, the speaker's known beliefs, influences the perceived coherence, strength, and persuasiveness of a SSA. Using an unobtrusive dependent variable (eye movements during reading), in Study 3 we showed that readers are sensitive to the internal coherence between a speaker's beliefs and the implied meaning of the argument. Finally, Study 4 revealed that this degree of internal coherence influences the perceived strength and persuasiveness of the argument. Together, these data indicate that SSAs are treated as a form of negative consequentialist argument. People infer that the speaker of a SSA opposes the initial proposal; therefore, SSAs are only perceived to be persuasive and conversationally relevant when the speaker's attitudes match this inference. PMID- 26886760 TI - In this issue: small B cell lymphomas, more than just a size. PMID- 26886761 TI - Broadband Photovoltaic Detectors Based on an Atomically Thin Heterostructure. AB - van der Waals junctions of two-dimensional materials with an atomically sharp interface open up unprecedented opportunities to design and study functional heterostructures. Semiconducting transition metal dichalcogenides have shown tremendous potential for future applications due to their unique electronic properties and strong light-matter interaction. However, many important optoelectronic applications, such as broadband photodetection, are severely hindered by their limited spectral range and reduced light absorption. Here, we present a p-g-n heterostructure formed by sandwiching graphene with a gapless band structure and wide absorption spectrum in an atomically thin p-n junction to overcome these major limitations. We have successfully demonstrated a MoS2 graphene-WSe2 heterostructure for broadband photodetection in the visible to short-wavelength infrared range at room temperature that exhibits competitive device performance, including a specific detectivity of up to 10(11) Jones in the near-infrared region. Our results pave the way toward the implementation of atomically thin heterostructures for broadband and sensitive optoelectronic applications. PMID- 26886762 TI - Salicylate-Induced Hearing Loss Trigger Structural Synaptic Modifications in the Ventral Cochlear Nucleus of Rats via Medial Olivocochlear (MOC) Feedback Circuit. AB - Lesion-induced cochlear damage can result in synaptic outgrowth in the ventral cochlear nucleus (VCN). Tinnitus may be associated with the synaptic outgrowth and hyperactivity in the VCN. However, it remains unclear how hearing loss triggers structural synaptic modifications in the VCN of rats subjected to salicylate-induced tinnitus. To address this issue, we evaluated tinnitus-like behavior in rats after salicylate treatment and compared the amplitude of the distortion product evoked otoacoustic emission (DPOAE) and auditory brainstem response (ABR) between control and treated rats. Moreover, we observed the changes in the synaptic ultrastructure and in the expression levels of growth associated protein (GAP-43), brain-derived neurotrophic factor (BDNF), the microglial marker Iba-1 and glial fibrillary acidic protein (GFAP) in the VCN. After salicylate treatment (300 mg/kg/day for 4 and 8 days), analysis of the gap prepulse inhibition of the acoustic startle showed that the rats were experiencing tinnitus. The changes in the DPOAE and ABR amplitude indicated an improvement in cochlear sensitivity and a reduction in auditory input following salicylate treatment. The treated rats displayed more synaptic vesicles and longer postsynaptic density in the VCN than the control rats. We observed that the GAP-43 expression, predominantly from medial olivocochlear (MOC) neurons, was significantly up-regulated, and that BDNF- and Iba-1-immunoreactive cells were persistently decreased after salicylate administration. Furthermore, GFAP immunoreactive astrocytes, which is associated with synaptic regrowth, was significantly increased in the treated groups. Our study revealed that reduced auditory nerve activity triggers synaptic outgrowth and hyperactivity in the VCN via a MOC neural feedback circuit. Structural synaptic modifications may be a reflexive process that compensates for the reduced auditory input after salicylate administration. However, massive increases in excitatory synapses in the VCN may represent a detrimental process that causes central hyperactivity, leading to tinnitus. PMID- 26886764 TI - Nanoscale characterization illustrates the cisplatin-mediated biomechanical changes of B16-F10 melanoma cells. AB - Cells reorganize their membrane biomechanical dynamics in response to environmental stimuli or inhibitors associated with their physiological/pathological processes, and disease therapeutics. To validate the biophysical dynamics during cell exposure to anti-cancer drugs, we investigate the nanoscale biological characterization in melanoma cells undergoing cisplatin treatment. Using atomic force microscopy, we demonstrate that the cellular morphology and membrane ultrastructure are altered after exposure to cisplatin. In contrast to their normal spindle-like shape, cisplatin causes cell deformation rendering cells flat and enlarged, which increases the cell area by 3-4 fold. Additionally, cisplatin decreases the topography height values for both the cytoplasmic and nuclear regions (by 40-80% and 60%, respectively). Furthermore, cisplatin increases the cytoplasmic root mean square roughness by 110-240% in correlation with the drug concentration and attenuates the nuclear RMS by 60%. Moreover, the cellular adhesion force was enhanced, while the Young's modulus elasticity was attenuated by ~2 and ~2.3 fold, respectively. F-actin phalloidin staining revealed that cisplatin enlarges the cell size through enhanced stress fiber formation and promotes cytoskeletal reorganization. Immunoblot analyses further revealed that the activities of focal adhesion proteins, such as FAK and c-Src, are upregulated by cisplatin through phosphorylation at tyrosine 397 and 530, respectively. Collectively, these results show that cisplatin-treated melanoma cells not only exhibit the upregulation of FAK-mediated signaling to enhance the cytoskeleton mechanical stretch, but also promote the cytoskeletal rearrangement resulting in 43% decrease in the cell modulus. These mechanisms thus promote the malignancy and invasiveness of the melanoma cells. PMID- 26886763 TI - Kinetics and Molecular Docking Study of an Anti-diabetic Drug Glimepiride as Acetylcholinesterase Inhibitor: Implication for Alzheimer's Disease-Diabetes Dual Therapy. AB - At the present time, treatment of two most common degenerative disorders of elderly population i.e., Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) is a major concern worldwide. As there are several evidences that proved strong linkages between these two disorders, the idea of using dual therapeutic agent for both the diseases might be considered as a good initiative. Earlier reports have revealed that oral anti-diabetic drugs such as peroxisome proliferator activated receptor gamma (PPARgamma) agonists (thiazolidinediones) when used in T2DM patients suffering from AD showed improved memory and cognition. However, the underlying mechanism still needs to be deciphered. Therefore, the present study was carried out to find whether glimepiride, an oral antidiabetic drug which is a PPARgamma agonist could inhibit the activity of acetylcholine esterase (AChE) enzyme. Actually, AChE inhibitors seize the breakdown of acetylcholine which forms the main therapeutic strategy for AD. Here, glimepiride showed dose dependent inhibitory activity against AChE enzyme with IC50 value of 235 MUM. Kinetic analysis showed competitive inhibition, which was verified by in silico docking studies. Glimepiride was found to interact with AChE enzyme at the same locus as that of substrate acetylcholine iodide (AChI). Interestingly, amino acid residues, Q71, Y72, V73, D74, W86, N87, Y124, S125, W286, F295, F297, Y337, F338 and Y341 of AChE were found to be common for 'glimepiride-AChE interaction' as well as 'AChI-AChE interaction'. Thus the present computational and kinetics study concludes that glimepiride and other thiazolidinediones derivatives could form the basis of future dual therapy against diabetes associated neurological disorders. PMID- 26886765 TI - Construction of CuS Nanoflakes Vertically Aligned on Magnetically Decorated Graphene and Their Enhanced Microwave Absorption Properties. AB - Hybrid nanocomposites with enhanced microwave absorption properties have been designed by growing CuS nanoflakes on magnetically decorated graphene, and the effect of special nanostructures on microwave absorption properties has been investigated. The structure of the nanocomposites was characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction (XRD), Raman spectroscopy, X ray photoelectron spectroscopy (XPS), field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), N2 adsorption-desorption, and vibrating sample magnetometer (VSM). The influence of cetyltrimethylammonium bromide (CTAB) on the morphology of CuS nanoflakes was also investigated. A possible formation process of the nanocomposites and the mechanism of microwave absorption were explained in detail. As an absorber, the nanocomposites with a filler loading of 20 wt % exhibited enhanced microwave absorption properties due to the special nanostructures, extra void space, and synergistic effect. The maximum reflection loss can reach -54.5 dB at 11.4 GHz, and the absorption bandwidths exceeding -10 dB are 4.5 GHz with a thickness of 2.5 mm, which can be adjusted by the thickness. The results indicate that the hybrid nanocomposites with enhanced microwave absorption properties and lightweight have a promising future in decreasing electromagnetic wave irradiation. PMID- 26886767 TI - A Molecular Dynamics Study of Tributyl Phosphate and Diamyl Amyl Phosphonate Self Aggregation in Dodecane and Octane. AB - A molecular dynamics model for tributyl phosphate (TBP) and diamyl amyl phosphonate (DAAP) is presented using the Generalized AMBER Force Field (GAFF) and the AM1-BCC method for calculated atomic charges with a modification to the phosphorus-containing dihedral parameters. The density and average molecular dipole in a neat liquid simulation, and dimerization in dodecane and octane diluents, compare favorably to experimental values. At low extractant concentration, investigation of the dimer structure reveals the offset "head-to head" orientation as the predominant structure over a range of TBP and DAAP concentrations with a phosphoryl oxygen separation distance between dimerized extractants of 3-5.5 A. At high extractant concentrations, a graph analysis of extractant aggregates was used to determine concentrations of each aggregate size and the average coordination number, which gives a measure of the linearity of the aggregates. For aggregates up to 7 extractant molecules, the mean free energy of association per molecule was found to be 0.55-0.59 and 0.72 kcal/mol for TBP and DAAP, respectively. In both diluents, TBP formed large aggregates more frequently than DAAP, and those aggregates were more nonlinear than their DAAP equivalents. This finding anticipates differences in aggregation chemistry between TBP and DAAP in PUREX extraction systems. PMID- 26886766 TI - Why Do Floral Perfumes Become Different? Region-Specific Selection on Floral Scent in a Terrestrial Orchid. AB - Geographically structured phenotypic selection can lead to adaptive divergence. However, in flowering plants, such divergent selection has rarely been shown, and selection on floral signals is generally little understood. In this study, we measured phenotypic selection on display size, floral color, and floral scent in four lowland and four mountain populations of the nectar-rewarding terrestrial orchid Gymnadenia odoratissima in two years. We also quantified population differences in these traits and pollinator community composition. Our results show positive selection on display size and positive, negative, or absence of selection on different scent compounds and floral color. Selection on the main scent compounds was consistently stronger in the lowlands than in the mountains, and lowland plants emitted higher amounts of most of these compounds. Pollinator community composition also differed between regions, suggesting different pollinators select for differences in floral volatiles. Overall, our study is the first to document consistent regional differences in selection on floral scent, suggesting this pattern of selection is one of the evolutionary forces contributing to regional divergence in floral chemical signaling. PMID- 26886768 TI - Repository Planning, Design, and Engineering: Part II-Equipment and Costing. AB - Part II of this article discusses and provides guidance on the equipment and systems necessary to operate a repository. The various types of storage equipment and monitoring and support systems are presented in detail. While the material focuses on the large repository, the requirements for a small-scale startup are also presented. Cost estimates and a cost model for establishing a repository are presented. The cost model presents an expected range of acquisition costs for the large capital items in developing a repository. A range of 5,000-7,000 ft(2) constructed has been assumed, with 50 frozen storage units, to reflect a successful operation with growth potential. No design or engineering costs, permit or regulatory costs, or smaller items such as the computers, software, furniture, phones, and barcode readers required for operations have been included. PMID- 26886769 TI - Secondary Guilt Syndrome May Have Led Nazi-persecuted Jewish Writers to Suicide. AB - Feelings of guilt have tormented Holocaust survivors, ranging from immediately after the liberation to later in life, for shorter or longer periods, and persisting for some throughout their entire post-war lives. Descriptions of the guilt experienced by survivors of the Nazi camps occupy an impressive amount of literature: "Why me?" was the question, when a younger and more able family member perished; "Why me?" when more productive members of the community perished; "Why me?" when a million and a half children were deprived of their lives. Many found the answer by retelling their stories, witnesses of what happened. This type of guilt is much different from the recently described phenomenon of survivor syndrome, namely the secondary guilt felt by Nazi persecuted Jewish writers. Despite successes in all aspects of their life, these writers developed a self-incriminating guilt due to their perceived inadequacy of communicating, particularly in light of the resurging anti-Semitism worldwide. This paper deals with the survival and suicides of Nazi-persecuted Jewish writers and offers a possible explanation for their late self-destructive acts. PMID- 26886770 TI - The Clinical Significance of Ependymal Enhancement at Presentation in Patients with Malignant Glioma. AB - INTRODUCTION: The current study evaluated the rate of ependymal enhancement and whether its presence influences survival of patients with malignant glioma (GBM). METHODS: A retrospective review of all patients who were treated in our institution from 2005 to 2011 was conducted. Data extracted from the medical records included age, date of diagnosis, co-morbidities, treatment regimen, and time of death. Magnetic resonance images (MRI) were evaluated for the presence of ependymal enhancement and its extent, and the correlation to survival was investigated. RESULTS: Between 2005 and 2011, 230 patients were treated for GBM. Eighty-nine patients were excluded from the study due to insufficient data, leaving 141 patients for analysis. Median age at diagnosis was 60 years. Sixty seven (40.6%) patients had evidence of ependymal enhancement on MRI (group A), and 70 (42.4%) patients did not have evidence of enhancement. The assessment of ependymal enhancement was inconclusive due to mass effect and ventricular compression that precluded accurate assessment for 28 (17%) patients (group C). Median survival was 14 months for group A (range, 12-16 months), 15.9 months for group B (range, 14.28-17.65 months), and 11.7 months for group C (range, 6.47 16.92 months) (P>0.05). A multivariate analysis to predict survival indicated that male gender (P=0.039), hypertension (P=0.012), and biopsy only compared to complete gross tumor resection (P=0.001) were significant for poor survival. CONCLUSIONS: Pretreatment ependymal enhancement on MRI was not found to be associated with poorer survival. These results might be due to better treatments options compared to prior reports. PMID- 26886771 TI - Diseases of Old Age in Two Paintings by Rembrandt. AB - Two paintings of older men by Rembrandt (1609-1669) are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person's response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt's own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject's foot and the second involving the subject's hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age. PMID- 26886773 TI - Public-Medicine Dissonance: Why in a World of Evidence-based Medicine? AB - The evolution of medicine is quite remarkable and astounding. Modern medicine is successfully treating or providing long-term control of conditions which in the not-so-distant past were lethal or resulted in permanent disability. The strong emphasis on evidence-based medicine in today's medical profession has led to a more organized approach toward evaluating the safety and efficacy of new medical treatments. Despite attempts to meet the complex needs of an ever-aging population, an almost cynical or inherent distrust of physicians in general and their medical claims is being increasingly noted. For many physicians this has led to an uncomfortable sense of professional frustration as doubt is cast on themselves or the medical profession in general when the expectations and goals of patients or their families are not achieved. The causes of this apparent malady of contemporary medicine are myriad and may be explored from various perspectives, depending on the particular issue. To understand better the issues and challenges involved, today's medical practitioner needs to be aware of the complex mix of organizational, professional, ethical, and at times anthropological perspectives contributing to this dissonance between medical professionals and the public. Improving our insight into the forces at work in this dissonance will help medical professionals improve medical services to the public and contribute to the preservation of medicine's admirable historical legacy. PMID- 26886772 TI - Prolactin-induced Subcellular Targeting of GLUT1 Glucose Transporter in Living Mammary Epithelial Cells. AB - BACKGROUND: Studying the biological pathways involved in mammalian milk production during lactation could have many clinical implications. The mammary gland is unique in its requirement for transport of free glucose into the cell for the synthesis of lactose, the primary carbohydrate in milk. OBJECTIVE: To study GLUT1 trafficking and subcellular targeting in living mammary epithelial cells (MEC) in culture. METHODS: Immunocytochemistry was used to study GLUT1 hormonally regulated subcellular targeting in human MEC (HMEC). To study GLUT1 targeting and recycling in living mouse MEC (MMEC) in culture, we constructed fusion proteins of GLUT1 and green fluorescent protein (GFP) and expressed them in CIT3 MMEC. Cells were maintained in growth medium (GM), or exposed to secretion medium (SM), containing prolactin. RESULTS: GLUT1 in HMEC localized primarily to the plasma membrane in GM. After exposure to prolactin for 4 days, GLUT1 was targeted intracellularly and demonstrated a perinuclear distribution, co-localizing with lactose synthetase. The dynamic trafficking of GFP-GLUT1 fusion proteins in CIT3 MMEC suggested a basal constitutive GLUT1 recycling pathway between an intracellular pool and the cell surface that targets most GLUT1 to the plasma membrane in GM. Upon exposure to prolactin in SM, GLUT1 was specifically targeted intracellularly within 90-110 minutes. CONCLUSIONS: Our studies suggest intracellular targeting of GLUT1 to the central vesicular transport system upon exposure to prolactin. The existence of a dynamic prolactin induced sorting machinery for GLUT1 could be important for transport of free glucose into the Golgi for lactose synthesis during lactation. PMID- 26886775 TI - Correction for the article "Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson's and Alzheimer's Disorders?" by Moussa B. H. Youdim. PMID- 26886774 TI - The Angelina Jolie Effect in Jewish Law: Prophylactic Mastectomy and Oophorectomy in BRCA Carriers. AB - BACKGROUND: Following the announcement of actress Angelina Jolie's prophylactic bilateral mastectomies and subsequent prophylactic oophorectomy, there has been a dramatic increase in interest in BRCA testing and prophylactic surgery. OBJECTIVE: To review current medical literature on the benefits of prophylactic mastectomy and oophorectomy among BRCA-positive women and its permissibility under Jewish law. RESULTS: Recent literature suggests that in BRCA-positive women who undergo prophylactic oophorectomy the risk of dying of breast cancer is reduced by 90%, the risk of dying of ovarian cancer is reduced by 95%, and the risk of dying of any cause is reduced by 77%. The risk of breast cancer is further reduced by prophylactic mastectomy. Prophylactic oophorectomy and prophylactic mastectomy pose several challenges within Jewish law that call into question the permissibility of surgery, including mutilation of a healthy organ, termination of fertility, self-wounding, and castration. A growing number of Jewish legal scholars have found grounds to permit prophylactic surgery among BRCA carriers, with some even obligating prophylactic mastectomy and oophorectomy. CONCLUSION: Current data suggest a significant reduction in mortality from prophylactic mastectomy and oophorectomy in BRCA carriers. While mutilation of healthy organs is intrinsically forbidden in Jewish law, the ability to preserve human life may contravene and even mandate prophylactic surgery. PMID- 26886777 TI - Obese Patients with Type 2 Diabetes on Conventional Versus Intensive Insulin Therapy: Efficacy of Low-Calorie Dietary Intervention. AB - INTRODUCTION: The aim of this prospective study was to assess the results of a standard low-calorie dietary intervention (7.5 MJ/day) on body weight (BW) and the metabolic profile of obese patients with type 2 diabetes mellitus (T2DM) on intensive insulin therapy (IIT: 4 insulin injections/day) versus conventional insulin therapy (CIT: 2/3 insulin injections/day). METHODS: A total of 60 patients (n = 60, 23 males and 37 postmenopausal females) were recruited and categorized into two groups according to the scheme of insulin treatment. Thirty were on IIT (13 males and 17 females) and an equal number on CIT (10 males and 20 females). BW, body mass index (BMI), HbA1c, and metabolic parameters were compared at 6 and 12 months after baseline. RESULTS: Significant reductions were observed in the BW, BMI, HbA1c (p <= 0.001 for all) and cholesterol (p <= 0.05) at 6 months post-intervention. At 1 year, median BW reduction was 4.5 kg (3.3, 5.8) for patients on IIT and 4.8 kg (3.6, 7.0) for those on CIT. The 12-month dietary intervention increased prevalence of normoglycemia in the IIT group and reduced the prevalence of obesity prevalence among the CIT participants (all p < 0.001). CIT patients with BW reduction >=5.0% demonstrated 11-fold greater chances of being normoglycemic (odds ratio 11.3, 95% CI 1.1-110.5). BW reduction >=7.0% was associated with CIT, being overweight, and having normal HDLc, LDLc, and cholesterol levels. A reduction in BW between 5.0% and 6.9% was associated with IIT, normoglycemia, and obesity. CONCLUSION: A 12-month 1800-kcal dietary intervention achieved significant BW and HbA1c reductions irrespectively of insulin regimen. CIT was associated with BW reduction greater than 8.0%, whereas IIT was associated with higher rates of normoglycemia. PMID- 26886776 TI - Two-Year Data from a Long-Term Phase IV Study of Recombinant Human Growth Hormone in Short Children Born Small for Gestational Age. AB - INTRODUCTION: This ongoing, prospective, open-label, non-comparative, multicenter phase IV study is evaluating the safety and efficacy of recombinant human growth hormone (rhGH; Omnitrope((r)), Sandoz GmbH) in short children born small for gestational age (SGA). Here we report data from patients who have completed 2 years' treatment. METHODS: Eligibility criteria included prepubertal children born SGA with growth disturbances defined as current height standard deviation score (HSDS) <-2.5 and parental adjusted SDS <-1; birth weight and/or length <-2 SDS; and failure of catch-up growth [height velocity (HV) SDS <0 during the last year] by 4 years of age or later. The primary study objective is to assess the long-term effect of Omnitrope treatment on the development of diabetes in short children born SGA. Secondary objectives include evaluation of efficacy, incidence and severity of adverse events (AEs), occurrence of malignancies during treatment, and detection of anti-rhGH antibodies during treatment. RESULTS: In total, 278 children have been enrolled and received study medication; 249 have completed 2 years of treatment. No child has developed diabetes mellitus during the first 2 years; no fasting glucose or 2-h oral glucose tolerance test value exceeded the pre-defined limits of >126 or >200 mg/dL, respectively. No adverse alterations in body mass were noted. Treatment-emergent AEs were experienced by 211 (76.2%) children; most of these were of mild-to-moderate intensity (99.3%) and considered unrelated to study medication (97.6%). Treatment with Omnitrope was effective; mean HSDS was -3.39 at baseline, -2.57 at 1 year and -2.15 at 2 years of treatment. Mean HVSDS (peak-centered) also improved, from -2.13 at baseline to +4.16 at 1 year and +2.23 at 2 years. CONCLUSION: In this second interim analysis, short children born SGA were safely and effectively treated with rhGH (Omnitrope), and 2 years' treatment had no major adverse impact on carbohydrate metabolism or body mass. FUNDING: Sandoz. PMID- 26886778 TI - Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice. AB - BACKGROUND: Thelper1 (Th1) lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1) macrophage activation or production of matrix degrading metalloproteinases (MMPs) and their tissue inhibitors, TIMPs. METHODS & RESULTS: We studied the effect of T-bet deletion in apolipoproteinE (ApoE) knockout mice fed a high fat diet (HFD) or normal chow diet (ND). Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS) and brachiocephalic artery (BCA) plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1), MMPs 2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3. CONCLUSIONS: Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased. PMID- 26886779 TI - A new multilayer reconstruction using nasal septal flap combined with fascia graft dural suturing for high-flow cerebrospinal fluid leak after endoscopic endonasal surgery. AB - This study aimed to evaluate the usefulness and reliability of a new endoscopic multilayer reconstruction using nasal septal flap (NSF) to prevent high-flow cerebrospinal fluid leak after endoscopic endonasal surgery. This study was a retrospective review on 97 patients who underwent multilayer reconstructions using NSF combined with fascia graft dural suturing after endoscopic endonasal surgery between July 2012 and March 2014. Patients were divided into two groups, third ventricle opening group and nonopening group, based on the presence of a direct connection between the third ventricle and the paranasal sinus after tumor removal. Furthermore, we compared this procedure with our previous reconstruction after resection of craniopharyngioma. Finally, we checked the patients who had postoperative prolonged discomfort of the nasal cavity for over a year. Postoperative cerebrospinal fluid (CSF) leak occurred in three patients (3.1 %): one from the third ventricle opening group and the remaining two from the nonopening group. External lumbar drain was performed after surgery in only seven patients (7.2 %). The incidence of postoperative CSF leak was similar in both groups, whereas the rate of craniopharyngioma in the third ventricle opening group was significantly higher. The incidence of postoperative CSF leak after resection of craniopharyngioma was not statistically significant but obviously higher in the previous group (12.2 %) compared with that in the present group (2.3 %). Twelve patients (12.4 %) had postoperative nasal discomfort of the nasal cavity for over a year. Multilayer reconstruction using NSF combined with fascia graft dural suturing is a more reliable method for preventing postoperative high flow CSF leakage after endoscopic endonasal surgery even if there is a direct connection between the third ventricle and the paranasal sinus. However, we should pay close attention especially to prolonged discomfort of the nasal cavity after harvesting NSF. PMID- 26886781 TI - Lung cancer stigma and patient-provider communication: a complex association. PMID- 26886780 TI - Frontal Bone Insufficiency in Gsk3beta Mutant Mice. AB - The development of the mammalian skull is a complex process that requires multiple tissue interactions and a balance of growth and differentiation. Disrupting this balance can lead to changes in the shape and size of skull bones, which can have serious clinical implications. For example, insufficient ossification of the bony elements leads to enlarged anterior fontanelles and reduced mechanical protection of the brain. In this report, we find that loss of Gsk3beta leads to a fully penetrant reduction of frontal bone size and subsequent enlarged frontal fontanelle. In the absence of Gsk3beta the frontal bone primordium undergoes increased cell death and reduced proliferation with a concomitant increase in Fgfr2-IIIc and Twist1 expression. This leads to a smaller condensation and premature differentiation. This phenotype appears to be Wnt independent and is not rescued by decreasing the genetic dose of beta catenin/Ctnnb1. Taken together, our work defines a novel role for Gsk3beta in skull development. PMID- 26886783 TI - Advances in family-based interventions in the neonatal ICU. AB - PURPOSE OF REVIEW: Despite advances in medical care, preterm infants remain at risk for many adverse outcomes. This article reviews findings from several recent neonatal ICU (NICU) interventions and a trial of a novel nurture-based approach, Family Nurture Intervention (FNI). RECENT FINDINGS: Recent trials reviewed here find positive effects of a variety of family-related interventions focused on parental guidance. These interventions target prescribed physical activities with infants, parents' stress, and the parents' ability to recognize their positive and negative behaviors with their infants. Beneficial effects include reductions in parenting stress, maternal anxiety, and depression. A different approach, FNI, is aimed at establishing mother-infant emotional connection. As in other trials, FNI also decreased maternal symptoms of anxiety and depression, and increased maternal sensitivity. Additionally, FNI led to positive short and long-term effects on infant neurobehavioral outcomes at term and 18 months. SUMMARY: A number of recent parent-based NICU interventions have been effective at reducing preterm parent stress. Another, FNI, has positive effects on both maternal and infant outcomes and promises to be cost-effective. Future decreases in long-term morbidity in preterm infants will increasingly rely on nonmedical interventions. Therefore, the rigorous development and testing of such interventions should be a high priority in perinatology research. PMID- 26886782 TI - Thiamin and Riboflavin in Human Milk: Effects of Lipid-Based Nutrient Supplementation and Stage of Lactation on Vitamer Secretion and Contributions to Total Vitamin Content. AB - While thiamin and riboflavin in breast milk have been analyzed for over 50 years, less attention has been given to the different forms of each vitamin. Thiamin monophosphate (TMP) and free thiamin contribute to total thiamin content; flavin adenine-dinucleotide (FAD) and free riboflavin are the main contributors to total riboflavin. We analyzed milk collected at 2 (n = 258) or 6 (n = 104), and 24 weeks (n = 362) from HIV-infected Malawian mothers within the Breastfeeding, Antiretrovirals and Nutrition (BAN) study, randomly assigned at delivery to lipid based nutrient supplements (LNS) or a control group, to investigate each vitamer's contribution to total milk vitamin content and the effects of supplementation on the different thiamin and riboflavin vitamers at early and later stages of lactation, and obtain insight into the transport and distribution of these vitamers in human milk. Thiamin vitamers were derivatized into thiochrome-esters and analyzed by high-performance liquid-chromatography fluorescence-detection (HPLC-FLD). Riboflavin and FAD were analyzed by ultra performance liquid-chromatography-tandem-mass-spectrometry (ULPC-MS/MS). Thiamin pyrophosphate (TPP), identified here for the first time in breast milk, contributed 1.9-4.5% to total thiamin. Free thiamin increased significantly from 2/6 to 24 weeks regardless of treatment indicating an active transport of this vitamer in milk. LNS significantly increased TMP and free thiamin only at 2 weeks compared to the control: median 170 versus 151 MUg/L (TMP), 13.3 versus 10.5 MUg/L (free thiamin, p<0.05 for both, suggesting an up-regulated active mechanism for TMP and free thiamin accumulation at early stages of lactation. Free riboflavin was consistently and significantly increased with LNS (range: 14.8 19.6 MUg/L (LNS) versus 5.0-7.4 MUg/L (control), p<0.001), shifting FAD:riboflavin relative amounts from 92-94:6-8% to 85:15%, indicating a preferred secretion of the free form into breast milk. The continuous presence of FAD in breast milk suggests an active transport and secretion system for this vitamer or possibly formation of this co-enymatic form in the mammary gland. PMID- 26886784 TI - Fetal interventions for congenital heart disease. AB - PURPOSE OF REVIEW: This article discusses the rationale, patient selection, technical aspects, and outcomes of percutaneous, ultrasound-guided fetal cardiac intervention (FCI) for structural congenital heart disease. RECENT FINDINGS: FCI is most commonly performed for three forms of congenital heart disease: severe aortic stenosis with evolving hypoplastic left heart syndrome (HLHS), pulmonary atresia with intact ventricular septum and evolving hypoplastic right heart syndrome, and HLHS with intact or highly restrictive atrial septum. For severe aortic stenosis and pulmonary atresia with intact ventricular septum, the goal of intervention is to alter the natural history such that a biventricular circulation may be achieved postnatally. A growing number of patients have achieved a biventricular circulation; however, patient selection and postnatal management strategy are essential for success. HLHS with intact or highly restrictive atrial septum is one of the most lethal forms of congenital heart disease, and the goal of FCI is to improve survival. Although the creation of an atrial communication in utero is technically feasible and may permit greater stability in the immediate postnatal period, significant improvements in survival have not yet been reported. SUMMARY: FCI is an evolving form of treatment for congenital heart disease that holds promise for select patients. Critical evaluation of both short and long-term outcomes is warranted. PMID- 26886786 TI - Identification of protein complexes of microsomes in rat adipocytes by native gel coupled with LC-ESI-QTOF. AB - The study of the composition of microsome proteins/complexes/interactions in adipocytes provides useful information for researchers related to energy metabolism disorders. The native gel coupled with LC-ESI-QTOF approach was employed here for separating protein complexes. We found a series of proteins functionally clustered in biological processes of protein metabolism, cellular carbohydrate catabolism, response to stimulus and wounding, macromolecular complex subunit organization, positive regulation of molecular function, regulation of programmed cell death and biomolecule transport. According to clustering of proteins' electrophoresis profiles across native gel fractions and bioinformatics data retrieval, protein complexes/interactions involved in protein metabolism, cellular carbohydrate catabolism, macromolecular complex subunit organization and biomolecule transport were identified. Besides, the results also revealed some functional linkages, which may provide useful information for discovering previously unknown interactions. The interaction between SSAO and ALDH2 was verified by co-immunoprecipitation. The native gel combining mass spectrometry approach appeared to be a useful tool for investigating microsome proteins and complexes to complement the traditional electrophoresis approaches. The native gel strategy together with our findings should facilitate future studies of the composition of rat adipocyte microsome protein complexes under different conditions. PMID- 26886787 TI - A Year in Review. PMID- 26886785 TI - Adverse consequences of neonatal antibiotic exposure. AB - PURPOSE OF REVIEW: Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. RECENT FINDINGS: Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. SUMMARY: The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely. PMID- 26886788 TI - Clinical significance of serum claudin-1 levels in melanoma patients. AB - Claudins are the most important structural and functional components of tight junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined. PMID- 26886789 TI - Palladium-catalysed transannular C-H functionalization of alicyclic amines. AB - Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline. PMID- 26886790 TI - Sensitivity of global terrestrial ecosystems to climate variability. AB - The identification of properties that contribute to the persistence and resilience of ecosystems despite climate change constitutes a research priority of global relevance. Here we present a novel, empirical approach to assess the relative sensitivity of ecosystems to climate variability, one property of resilience that builds on theoretical modelling work recognizing that systems closer to critical thresholds respond more sensitively to external perturbations. We develop a new metric, the vegetation sensitivity index, that identifies areas sensitive to climate variability over the past 14 years. The metric uses time series data derived from the moderate-resolution imaging spectroradiometer (MODIS) enhanced vegetation index, and three climatic variables that drive vegetation productivity (air temperature, water availability and cloud cover). Underlying the analysis is an autoregressive modelling approach used to identify climate drivers of vegetation productivity on monthly timescales, in addition to regions with memory effects and reduced response rates to external forcing. We find ecologically sensitive regions with amplified responses to climate variability in the Arctic tundra, parts of the boreal forest belt, the tropical rainforest, alpine regions worldwide, steppe and prairie regions of central Asia and North and South America, the Caatinga deciduous forest in eastern South America, and eastern areas of Australia. Our study provides a quantitative methodology for assessing the relative response rate of ecosystems--be they natural or with a strong anthropogenic signature--to environmental variability, which is the first step towards addressing why some regions appear to be more sensitive than others, and what impact this has on the resilience of ecosystem service provision and human well-being. PMID- 26886791 TI - Corrigendum: Bees prefer foods containing neonicotinoid pesticides. PMID- 26886792 TI - Ecology: Vegetation's responses to climate variability. PMID- 26886793 TI - The mid-developmental transition and the evolution of animal body plans. AB - Animals are grouped into ~35 'phyla' based upon the notion of distinct body plans. Morphological and molecular analyses have revealed that a stage in the middle of development--known as the phylotypic period--is conserved among species within some phyla. Although these analyses provide evidence for their existence, phyla have also been criticized as lacking an objective definition, and consequently based on arbitrary groupings of animals. Here we compare the developmental transcriptomes of ten species, each annotated to a different phylum, with a wide range of life histories and embryonic forms. We find that in all ten species, development comprises the coupling of early and late phases of conserved gene expression. These phases are linked by a divergent 'mid developmental transition' that uses species-specific suites of signalling pathways and transcription factors. This mid-developmental transition overlaps with the phylotypic period that has been defined previously for three of the ten phyla, suggesting that transcriptional circuits and signalling mechanisms active during this transition are crucial for defining the phyletic body plan and that the mid-developmental transition may be used to define phylotypic periods in other phyla. Placing these observations alongside the reported conservation of mid-development within phyla, we propose that a phylum may be defined as a collection of species whose gene expression at the mid-developmental transition is both highly conserved among them, yet divergent relative to other species. PMID- 26886794 TI - Structural basis for activity regulation of MLL family methyltransferases. AB - The mixed lineage leukaemia (MLL) family of proteins (including MLL1-MLL4, SET1A and SET1B) specifically methylate histone 3 Lys4, and have pivotal roles in the transcriptional regulation of genes involved in haematopoiesis and development. The methyltransferase activity of MLL1, by itself severely compromised, is stimulated by the three conserved factors WDR5, RBBP5 and ASH2L, which are shared by all MLL family complexes. However, the molecular mechanism of how these factors regulate the activity of MLL proteins still remains poorly understood. Here we show that a minimized human RBBP5-ASH2L heterodimer is the structural unit that interacts with and activates all MLL family histone methyltransferases. Our structural, biochemical and computational analyses reveal a two-step activation mechanism of MLL family proteins. These findings provide unprecedented insights into the common theme and functional plasticity in complex assembly and activity regulation of MLL family methyltransferases, and also suggest a universal regulation mechanism for most histone methyltransferases. PMID- 26886797 TI - Autoimmunity: Antigen-specific immunotherapy. PMID- 26886795 TI - Inhibiting fungal multidrug resistance by disrupting an activator-Mediator interaction. AB - Eukaryotic transcription activators stimulate the expression of specific sets of target genes through recruitment of co-activators such as the RNA polymerase II interacting Mediator complex. Aberrant function of transcription activators has been implicated in several diseases. However, therapeutic targeting efforts have been hampered by a lack of detailed molecular knowledge of the mechanisms of gene activation by disease-associated transcription activators. We previously identified an activator-targeted three-helix bundle KIX domain in the human MED15 Mediator subunit that is structurally conserved in Gal11/Med15 Mediator subunits in fungi. The Gal11/Med15 KIX domain engages pleiotropic drug resistance transcription factor (Pdr1) orthologues, which are key regulators of the multidrug resistance pathway in Saccharomyces cerevisiae and in the clinically important human pathogen Candida glabrata. The prevalence of C. glabrata is rising, partly owing to its low intrinsic susceptibility to azoles, the most widely used antifungal agent. Drug-resistant clinical isolates of C. glabrata most commonly contain point mutations in Pdr1 that render it constitutively active, suggesting that this transcriptional activation pathway represents a linchpin in C. glabrata multidrug resistance. Here we perform sequential biochemical and in vivo high-throughput screens to identify small-molecule inhibitors of the interaction of the C. glabrata Pdr1 activation domain with the C. glabrata Gal11A KIX domain. The lead compound (iKIX1) inhibits Pdr1-dependent gene activation and re-sensitizes drug-resistant C. glabrata to azole antifungals in vitro and in animal models for disseminated and urinary tract C. glabrata infection. Determining the NMR structure of the C. glabrata Gal11A KIX domain provides a detailed understanding of the molecular mechanism of Pdr1 gene activation and multidrug resistance inhibition by iKIX1. We have demonstrated the feasibility of small-molecule targeting of a transcription factor-binding site in Mediator as a novel therapeutic strategy in fungal infectious disease. PMID- 26886796 TI - Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis. AB - The orientation of cell division along the long axis of the interphase cell--the century-old Hertwig's rule--has profound roles in tissue proliferation, morphogenesis, architecture and mechanics. In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbour topology, and planar polarity pathways. At mitosis, epithelial cells usually adopt a rounded shape to ensure faithful chromosome segregation and to promote morphogenesis. The mechanisms underlying interphase cell shape sensing in tissues are therefore unknown. Here we show that in Drosophila epithelia, tricellular junctions (TCJs) localize force generators, pulling on astral microtubules and orienting cell division via the Dynein-associated protein Mud independently of the classical Pins/Galphai pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJs emerge from a general geometric property of TCJ distributions in epithelial tissues. Thus, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues. PMID- 26886798 TI - Adult restoration of Shank3 expression rescues selective autistic-like phenotypes. AB - Because autism spectrum disorders are neurodevelopmental disorders and patients typically display symptoms before the age of three, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigate the developmental requirement of Shank3 in mice, a prominent monogenic autism gene that is estimated to contribute to approximately 1% of all autism spectrum disorder cases. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density macromolecular signalling complex. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic like behaviours including anxiety, social interaction deficits, and repetitive behaviour. We generated a novel Shank3 conditional knock-in mouse model, and show that re-expression of the Shank3 gene in adult mice led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provide behavioural evidence that certain behavioural abnormalities including social interaction deficit and repetitive grooming behaviour could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results reveal the profound effect of post developmental activation of Shank3 expression on neural function, and demonstrate a certain degree of continued plasticity in the adult diseased brain. PMID- 26886799 TI - Expanding antigen-specific regulatory networks to treat autoimmunity. AB - Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4(+) T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena. Ten pMHCII based nanomedicines show similar biological effects, regardless of genetic background, prevalence of the cognate T-cell population or MHC restriction. These nanomedicines promote the differentiation of disease-primed autoreactive T cells into TR1-like cells, which in turn suppress autoantigen-loaded antigen-presenting cells and drive the differentiation of cognate B cells into disease-suppressing regulatory B cells, without compromising systemic immunity. pMHCII-based nanomedicines thus represent a new class of drugs, potentially useful for treating a broad spectrum of autoimmune conditions in a disease-specific manner. PMID- 26886801 TI - Performance on the Functional Movement Screen Is Related to Hop Performance But Not to Hip and Knee Strength in Collegiate Football Players. AB - OBJECTIVE: To define the relationship between Functional Movement Screen (FMS) scores and hop performance, hip strength, and knee strength in collegiate football players. DESIGN: Cross-sectional cohort. PARTICIPANTS: Freshmen of a Division I collegiate American football team (n = 59). MAIN OUTCOME MEASURES: The athletes performed the FMS, and also a variety of hop tests, isokinetic knee strength, and isometric hip strength tasks. We recorded total FMS score, peak strength, and hop performance, and we calculated asymmetries between legs on the different tasks. Spearman correlation coefficients quantified the relationships between these measures, and chi analyses compared the number of athletes with asymmetries on the different tasks. RESULTS: We observed significant correlations (r = 0.38-0.56, P <= 0.02) between FMS scores and hop distance but not between FMS scores and hip or knee strength (all P >= 0.21). The amount of asymmetry on the FMS test was significantly correlated to the amount of asymmetry on the timed 6-m hop (r = 0.44, P < 0.01) but not to hip or knee strength asymmetries between limbs (all P >= 0.34). CONCLUSIONS: Functional Movement Screen score was positively correlated to hop distance, and limb asymmetry in FMS tasks was correlated to limb asymmetry in 6-m hop time in football players. No significant correlations were observed between FMS score and hip and knee strength or between FMS asymmetry and asymmetries in hip and knee strength between limbs. These results indicate that a simple hop for distance test may be a time-efficient and cost-efficient alternative to FMS testing in athletes and that functional asymmetries between limbs do not coincide with strength asymmetries. PMID- 26886800 TI - Ancient gene flow from early modern humans into Eastern Neanderthals. AB - It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought. PMID- 26886802 TI - Five-Year Experience with Screening Electrocardiograms in National Collegiate Athletic Association Division I Athletes. AB - OBJECTIVE: (1) Compare rates of abnormal screening electrocardiograms (ECGs) using updated criteria compared with older criteria. (2) Compare rates of abnormal ECGs by ethnicity. (3) Evaluate ability of ECG criteria to detect the predicted number of athletes with previously undetected cardiovascular abnormalities. DESIGN: Prospective and retrospective review of ECGs. During the prospective portion of the study, the 2005 European Society of Cardiology criteria were used from 2008 to July 2011 and the 2011 Stanford criteria were used from August 2011 to 2013. Retrospectively, all ECGs were reevaluated using the 2011 Stanford criteria, 2013 Seattle criteria, and 2014 Sharma Refined criteria. SETTING: Division I National Collegiate Athletic Association University. PARTICIPANTS: 874 incoming athletes over a 5-year period. INTERVENTIONS: ECG screening program. MAIN OUTCOME MEASURES: Number of abnormal ECGs and number of athletes with newly discovered cardiac abnormalities. RESULTS: Abnormal ECG rates were the 2005 European criteria 10.7%, 2011 Stanford criteria 6.6%, 2013 Seattle criteria 2.8%, and 2014 Sharma Refined criteria 2.8%. In black athletes, the Stanford criteria resulted in more abnormal ECGs compared with Seattle or Sharma Refined. Three athletes were found to have a previously undetected cardiac abnormality (2 with hypertrophic cardiomyopathy and 1 with preexcitation). CONCLUSIONS: More recent ECG screening criteria substantially reduce the abnormal ECG rate and thus the number of athletes requiring additional testing. ECG screening criteria identified the predicted number (1/300) of young athletes with serious underlying cardiovascular disease. These criteria prompt not only additional cardiovascular testing but also a more thorough cardiovascular history. PMID- 26886804 TI - Wide field of view multifocal scanning microscopy with sparse sampling. AB - We propose to use sparsely sampled line scans with a sparsity-based reconstruction method to obtain images in a wide field of view (WFOV) multifocal scanning microscope. In the WFOV microscope, we used a holographically generated irregular focus grid to scan the sample in one dimension and then reconstructed the sample image from line scans by measuring the transmission of the foci through the sample during scanning. The line scans were randomly spaced with average spacing larger than the Nyquist sampling requirement, and the image was recovered with sparsity-based reconstruction techniques. With this scheme, the acquisition data can be significantly reduced and the restriction for equally spaced foci positions can be removed, indicating simpler experimental requirement. We built a prototype system and demonstrated the effectiveness of the reconstruction by recovering microscopic images of a U.S. Air Force target and an onion skin cell microscope slide with 40, 60, and 80% missing data with respect to the Nyquist sampling requirement. PMID- 26886803 TI - Reconstruction of explicit structural properties at the nanoscale via spectroscopic microscopy. AB - The spectrum registered by a reflected-light bright-field spectroscopic microscope (SM) can quantify the microscopically indiscernible, deeply subdiffractional length scales within samples such as biological cells and tissues. Nevertheless, quantification of biological specimens via any optical measures most often reveals ambiguous information about the specific structural properties within the studied samples. Thus, optical quantification remains nonintuitive to users from the diverse fields of technique application. In this work, we demonstrate that the SM signal can be analyzed to reconstruct explicit physical measures of internal structure within label-free, weakly scattering samples: characteristic length scale and the amplitude of spatial refractive index (RI) fluctuations. We present and validate the reconstruction algorithm via finite-difference time-domain solutions of Maxwell's equations on an example of exponential spatial correlation of RI. We apply the validated algorithm to experimentally measure structural properties within isolated cells from two genetic variants of HT29 colon cancer cell line as well as within a prostate tissue biopsy section. The presented methodology can lead to the development of novel biophotonics techniques that create two-dimensional maps of explicit structural properties within biomaterials: the characteristic size of macromolecular complexes and the variance of local mass density. PMID- 26886805 TI - Simultaneous blood flow and blood oxygenation measurements using a combination of diffuse speckle contrast analysis and near-infrared spectroscopy. AB - A combined diffuse speckle contrast analysis (DSCA)-near-infrared spectroscopy (NIRS) system is proposed to simultaneously measure qualitative blood flow and blood oxygenation changes in human tissue. The system employs an optical switch to alternate two laser sources at two different wavelengths and a CCD camera to capture the speckle image. Therefore, an optical density can be measured from two wavelengths for NIRS measurements and a speckle contrast can be calculated for DSCA measurements. In order to validate the system, a flow phantom test and an arm occlusion protocol for arterial and venous occlusion were performed. Shorter exposure times (<1 ms ) show a higher drop (between 50% and 66%) and recovery of 1/K2S values after occlusion (approximately 150%), but longer exposure time (3 ms) shows more consistent hemodynamic changes. For four subjects, the 1/K2S values dropped to an average of 82.1+/-4.0% during the occlusion period and the average recovery of 1/K2S values after occlusion was 109.1+/-0.8% . There was also an approximately equivalent amplitude change in oxyhemoglobin (OHb) and deoxyhemoglobin (RHb) during arterial occlusion (max RHb=0.0085+/-0.0024 mM/DPF, min OHb=-0.0057+/-0.0044 mM/DPF). The sensitivity of the system makes it a suitable modality to observe qualitative hemodynamic trends during induced physiological changes. PMID- 26886806 TI - Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model. AB - Online light dosimetry with real-time feedback was applied for temoporfin mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2. PMID- 26886807 TI - Efficacy of Vitamin D3 Supplementation on Osseointegration of Implants. AB - PURPOSE: The aim was to systematically review the efficacy of vitamin D3 (VD3) supplementation on the osseointegration of implants. METHODS: The addressed focused question was "does VD3 supplementation affect osseointegration around implants?" Indexed databases were searched from 1969 up to and including March 2015 using various key words including: "Bone to implant contact"; "implant"; "vitamin D"; and "osseointegration." Letters to the editor, case reports/case series, reviews, and articles published in languages other than English were excluded. The pattern of the present systematic review was customized to primarily summarize the pertinent data. RESULTS: Six experimental studies (4 in rodents and 2 in rabbits) were included. Number of titanium implants placed ranged between 28 and 100 implants. Results from 5 studies showed that VD3 supplementation enhanced new bone formation and/or bone to implant contact (BIC) around implants. One study showed no significant difference in BIC and new bone formation around VD3 coated and noncoated implants. One study reported that insulin therapy with adjunct VD3 supplementation enhances new bone formation around implants in diabetic rats than when insulin replacement therapy is used alone. CONCLUSION: Efficacy of VD3 supplementation on osseointegration of implants remains controversial and requires further investigations. PMID- 26886808 TI - Clinical Outcomes After Immediate and Late Implant Loading for a Single Missing Tooth in the Anterior Maxilla. AB - PURPOSE: This study compared the clinical outcomes of 1-year follow-up of immediate and late implant loading after implant restoration of a single tooth in the anterior maxilla. MATERIALS AND METHODS: Thirty-three patients with missing teeth in the anterior maxilla were included in this study (18 immediate loading and 15 late loading). Standard periapical radiographs were obtained to evaluate the vertical bone loss around the implant. For both implant groups, periimplant parameters (probing depth, gingival bleeding index, gingival index (GI), modified plaque index, width of keratinized gingiva) were evaluated. RESULTS: There were no significant differences in bone loss, the widths of keratinized gingiva, the GI, and modified plaque index between the immediate implant loading and late implant loading groups (P > 0.05). A significant difference in the probing depth was observed between these groups at the initial and 1-month evaluations (P < 0.05). Significant differences in bleeding indices between these groups were observed at months 3 and 6 (P < 0.05). CONCLUSIONS: When selecting appropriate patients (adequate primary stability, patient compliance with the surgeon's recommendations), immediate implant loading may be an alternative method to late loading protocol for replacement of a missing tooth in anterior maxilla. PMID- 26886809 TI - Silent Bias: Challenges, Obstacles, and Strategies for Leadership Development in Academic Medicine-Lessons From Oral Histories of Women Professors at the University of Kansas. AB - PURPOSE: Despite dramatic increases in female learners and junior faculty, a significant gap remains in female leadership in academic medicine. To assess challenges and obstacles encountered, strategies for academic success, and lessons learned for leadership development, the authors conducted an in-depth study of women full professors. METHOD: The authors used a qualitative oral history approach, interviewing 87% of the cohort of female full professors at one Midwestern medical school in 2013 using a pretested, open-ended, semistructured interview guide. Interviews were videotaped and the audio recordings transcribed. Content was sorted into categories and key themes identified within each category. RESULTS: Participants described significant challenges: being treated with "silent bias," "being ignored," and being seen as an "other." Coping strategies included downplaying, keeping a distance, employing humor, and using symbols (e.g., white coat) to carefully present themselves. Explanations for success included intelligence, meritocracy, being even-tempered, and carefully constructing femininity. The participants recommended individual skills and actions to prepare for leadership development. Virtually all women could describe an individual mentor (sponsor), usually male, who provided essential assistance for their career success. At the same time, they stressed the importance of institutional support for diversity, especially with child care. CONCLUSIONS: Attaining "full professor" status is the pinnacle of academic success. Women who successfully navigated this academic ladder describe significant external and internal challenges that require multiple strategies to overcome. Leadership development entails a combination of individual support through mentors and sponsors, self-education and reflection, and organizational structural support to promote diversity. PMID- 26886810 TI - Taking Risk: Early Results From Teaching Hospitals' Participation in the Center for Medicare and Medicaid Innovation Bundled Payments for Care Improvement Initiative. AB - The authors describe observations from the 27 teaching hospitals constituting the Association of American Medical Colleges (AAMC) cohort in the Center for Medicare and Medicaid Innovation (CMMI) Bundled Payments for Care Improvement (BPCI) initiative. CMMI introduced BPCI in August 2011 and selected the first set of participants in January 2013. BPCI participants enter into Medicare payment arrangements for episodes of care for which they take financial risk. The first round of participants entered risk agreements on October 1, 2013 and January 1, 2014. In April 2014, CMMI selected additional participants who started taking financial risk in 2015. Selected episodes include congestive heart failure (CHF), major joint replacement (MJR), and cardiac valve surgery. The AAMC cohort of participating hospitals selected clinical conditions on the basis of patient volume, opportunity to impact savings and quality, organizational and clinical team readiness, and prior process improvement experience. Early financial results suggest that focused attention to postacute care utilization and outcomes, rapid changes in care processes, program pricing rules, and team composition drove savings and losses. The first cohort of participants generated savings in MJR, CHF, and cardiac valve episodes; losses were experienced in stroke, percutaneous coronary intervention, and spine surgery. Although about one-quarter of U.S. teaching hospitals are participating in BPCI, the proliferation of existing and new payment models, as well as the 2015 announcement to increasingly pay providers according to value, mandates close scrutiny of program outcomes. The authors conclude by proposing additional opportunities for research related to alternative payment models. PMID- 26886811 TI - Proton-Coupled Electron Transfer and a Tyrosine-Histidine Pair in a Photosystem II-Inspired beta-Hairpin Maquette: Kinetics on the Picosecond Time Scale. AB - Photosystem II (PSII) and ribonucleotide reductase employ oxidation and reduction of the tyrosine aromatic ring in radical transport pathways. Tyrosine-based reactions involve either proton-coupled electron transfer (PCET) or electron transfer (ET) alone, depending on the pH and the pKa of tyrosine's phenolic oxygen. In PSII, a subset of the PCET reactions are mediated by a tyrosine histidine redox-driven proton relay, YD-His189. Peptide A is a PSII-inspired beta hairpin, which contains a single tyrosine (Y5) and histidine (H14). Previous electrochemical characterization indicated that Peptide A conducts a net PCET reaction between Y5 and H14, which have a cross-strand pi-pi interaction. The kinetic impact of H14 has not yet been explored. Here, we address this question through time-resolved absorption spectroscopy and 280-nm photolysis, which generates a neutral tyrosyl radical. The formation and decay of the neutral tyrosyl radical at 410 nm were monitored in Peptide A and its variant, Peptide C, in which H14 is replaced by cyclohexylalanine (Cha14). Significantly, both electron transfer (ET, pL 11, L = lyonium) and PCET (pL 9) were accelerated in Peptide A and C, compared to model tyrosinate or tyrosine at the same pL. Increased electronic coupling, mediated by the peptide backbone, can account for this rate acceleration. Deuterium exchange gave no significant solvent isotope effect in the peptides. At pL 9, but not at pL 11, the reaction rate decreased when H14 was mutated to Cha14. This decrease in rate is attributed to an increase in reorganization energy in the Cha14 mutant. The Y5-H14 mechanism in Peptide A is reminiscent of proton- and electron-transfer events involving YD-H189 in PSII. These results document a mechanism by which proton donors and acceptors can regulate the rate of PCET reactions. PMID- 26886812 TI - Transformative Theatre: A Promising Educational Tool for Improving Health Encounters With LGBT Older Adults. AB - Lesbian, gay, bisexual, or transgender (LGBT) older adults are often unaware or fearful of aging services that contribute to greater vulnerability, isolation, and risk when services are needed. In addition, they may perceive or experience bias in health care encounters. Providers may not recognize their own biases or their impact on such encounters. In response, a group of LGBT community activists, aging professionals, researchers, and a theatre ensemble developed an interactive theatre experience, described herein, that portrays challenges faced by LGBT older adults needing services. Goals included raising awareness among LGBT older adults and providers about issues such as the limited legal rights of partners, limited family support, and fear of being mistreated as a result of homophobia. Evaluations and feedback reflected the potential of interactive theatre to engage people in sensitive discussions that can lead to increased awareness, reduced bias, practice change, and ultimately improved care for LGBT older adults. PMID- 26886813 TI - Rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis. AB - Tropheryma Whipplei can induce rheumatism mimicking SpA or RA, but even more rampant bacterial/viral infections in epiphyseal bones could also contribute to the onset of RA and SpA. Indeed, as bone marrow stem cell niches are enriched in Tregs and myeloid derived suppressor cells, these areas are favourable for the persistence of quiescent viruses and/or dormant bacteria. This review focuses on the possibility that such silent infections of bone marrow stem cell niches might contribute to the pathogenesis of SpA and RA, at least during their onset. Some infections can affect the bone marrow mesenchymal stem cells, which can transmit these pathogens to their progeny. Transient but repeated revivals of viruses or dormant bacteria could promote the conversion of marrow regulatory T cells into effector phenotypes, leading to autoimmunity in the epiphyseal bone marrow, entheses and adjacent synovium. This scenario would also fit the flares of rheumatic disorders and explain why some joints or enthuses can be severely involved whereas their neighbours remain intact. The efficiency of anti-TNF drugs does not rule out a role of persistent infections in SpA and RA. These drugs do not affect chlamydial clearance, or the reactivation of latent Salmonella enterica serovar Typhimurium in mice or Epstein-Barr virus in humans. Anti-TNF might even prevent, rather than foster, the revival of dormant bacteria and viruses in marrow stem cell niches. Indeed, anti-TNF enhance the maturation of the immunosuppressive immature myeloid cells around stem cells into dendritic cells and macrophages, thus restoring immune responses in these areas. PMID- 26886814 TI - Effect of stents coated with a combination of sirolimus and alpha-lipoic acid in a porcine coronary restenosis model. AB - The aim of this study was to evaluate antiproliferative sirolimus- and antioxidative alpha-lipoic acid (ALA)-eluting stents using biodegradable polymer [poly-L-lactic acid (PLA)] in a porcine coronary overstretch restenosis model. Forty coronary arteries of 20 pigs were randomized into four groups in which the coronary arteries had a bare metal stent (BMS, n = 10), ALA-eluting stent with PLA (AES, n = 10), sirolimus-eluting stent with PLA (SES, n = 10), or sirolimus- and ALA-eluting stent with PLA (SAS, n = 10). A histopathological analysis was performed 28 days after the stenting. The ALA and sirolimus released slowly over 30 days. There were no significant differences between groups in the injury or inflammation score; however, there were significant differences in the percent area of stenosis (56.2 +/- 11.78% in BMS vs. 51.5 +/- 12.20% in AES vs. 34.7 +/- 7.23% in SES vs. 28.7 +/- 7.30% in SAS, P < 0.0001) and fibrin score [1.0 (range 1.0-1.0) in BMS vs. 1.0 (range 1.0-1.0) in AES vs. 2.0 (range 2.0-2.0) in SES vs. 2.0 (range 2.0-2.0) in SAS, P < 0.0001] between the four groups. The percent area of stenosis based on micro-computed tomography corresponded with the restenosis rates based on histopathological stenosis in different proportions in the four groups (54.8 +/- 7.88% in BMS vs. 50.4 +/- 14.87% in AES vs. 34.5 +/- 7.22% in SES vs. 28.9 +/- 7.22% in SAS, P < 0.05). SAS showed a better neointimal inhibitory effect than BMS, AES, and SES at 1 month after stenting in a porcine coronary restenosis model. Therefore, SAS with PLA can be a useful drug combination for coronary stent coating to suppress neointimal hyperplasia. PMID- 26886815 TI - Is dialdehyde starch a valuable cross-linking agent for collagen/elastin based materials? AB - Collagen and elastin are the main structural proteins in mammal bodies. They provide mechanical support, strength, and elasticity to various organs and tissues, e.g. skin, tendons, arteries, and bones. They are readily available, biodegradable, biocompatible and they stimulate cell growth. The physicochemical properties of collagen and elastin-based materials can be modified by cross linking. Glutaraldehyde is one of the most efficient cross-linking agents. However, the unreacted molecules can be released from the material and cause cytotoxic reactions. Thus, the aim of our work was to investigate the influence of a safer, macromolecular cross-linking agent--dialdehyde starch (DAS). The properties of hydrogels based on collagen/elastin mixtures (95/5, 90/10) containing 5 and 10% of DAS and neutralized via dialysis against deionized water were tested. The homogenous, transparent, stiff hydrogels were obtained. The DAS addition causes the formation of intermolecular cross-linking bonds but does not affect the secondary structure of the proteins. As a result, the thermal stability, mechanical strength, and, surprisingly, swelling ability increased. At the same time, the surface properties test and in vitro study show that the materials are attractive for 3T3 cells. Moreover, the materials containing 10% of DAS are more resistant to enzymatic degradation. PMID- 26886816 TI - The response of osteoblastic MC3T3-E1 cells to micro- and nano-textured, hydrophilic and bioactive titanium surfaces. AB - The aim of the present work was to investigate the morphology and activity of the murine osteoblastic cell line MC3T3 on control smooth (Machined), commercially available rough (ZT) titanium discs, and on titanium samples obtained by modifying the ZT treatment protocol, and herein labelled as ZTF, ZTM and ZTFM. Cells were evaluated at SEM and immunofluorescence for morphology and cell-to cell interactions and by MTT assay and real time PCR for cell growth and function. Microscopy showed that ZT modified protocols could differently affect cell shape and distribution. All the tested surfaces showed good biocompatibility by viability assay. However, cells on smoother surfaces appeared to express higher levels of transcript for Collagen 1a1, the main component of extracellular matrix, by real time PCR. Expression of the early differentiation marker Alkaline Phosphatase was higher on ZTF surfaces and ZTM enhanced the expression of later osteoblastic markers Osteoprotegerin and Osteocalcin. Noteworthy, the expression of Connexin 43, a component of cell-to-cell contacts and hemichannels, followed a similar pattern to differentiation marker genes and was higher in cells on ZTM surfaces, consistently with the microscopic observation of cell clusters. Taken together, this data showed that ZTF and ZTM treatment protocols appeared to improve the basal sand-blasting/acid-etching ZT procedure with ZTM surfaces promoting the most mature stage of differentiation. PMID- 26886817 TI - Production of new 3D scaffolds for bone tissue regeneration by rapid prototyping. AB - The incidence of bone disorders, whether due to trauma or pathology, has been trending upward with the aging of the worldwide population. The currently available treatments for bone injuries are rather limited, involving mainly bone grafts and implants. A particularly promising approach for bone regeneration uses rapid prototyping (RP) technologies to produce 3D scaffolds with highly controlled structure and orientation, based on computer-aided design models or medical data. Herein, tricalcium phosphate (TCP)/alginate scaffolds were produced using RP and subsequently their physicochemical, mechanical and biological properties were characterized. The results showed that 60/40 of TCP and alginate formulation was able to match the compression and present a similar Young modulus to that of trabecular bone while presenting an adequate biocompatibility. Moreover, the biomineralization ability, roughness and macro and microporosity of scaffolds allowed cell anchoring and proliferation at their surface, as well as cell migration to its interior, processes that are fundamental for osteointegration and bone regeneration. PMID- 26886818 TI - Impact of decellularization on porcine myocardium as scaffold for tissue engineered heart tissue. AB - Decellularized myocardium has been proposed to construct tissue engineered heart tissue, providing the advantage of natural extracellular architecture. Various decellularization protocols have been developed, but the impact of individual decellularization reagent in the protocol remains unclear. The aim of this study is to evaluate the structural impact of three commonly used decellularization reagents on the porcine myocardium. We decellularized porcine heart tissue with trypsin, Triton X-100 or SDS, and analyzed the morphological characteristics of the remaining tissue by SEM, AFM and two-photon LSM. We further recellularized the scaffold with rat myocardial fibroblasts and cardiomyocytes separately. According to the H&E staining and DNA quantification, SDS decellularized more efficiently in comparison to the other two reagents. Moreover, we found distinct surface microarchitecture differences among groups. The changed structure of tissue might result in varied proliferation myocardial fibroblasts and biophysical performance of the engineered heart tissue. This study demonstrated that the microstructure of decellularized porcine heart tissue vary with decellularization agents. Compared to trypsin and Triton X-100, SDS not only decellularized more efficiently but also preserved the biocompatible microstructure of ECM for recellularization. PMID- 26886819 TI - Graphene oxide and titanium: synergistic effects on the biomineralization ability of osteoblast cultures. AB - Graphene oxide (GO) has attracted remarkable attention in recent years due to properties such as extremely large surface area, biocompatibility, biostability, and easy chemical functionalization. Osteoblasts underlie the deposition of hydroxyapatite crystals in the bone protein matrix during biomineralization; hydroxyapatite deposition involves extracellular matrix vesicles that are rich in alkaline phosphatase (ALP). Here, we have investigated how GO affects osteoblast viability, ALP activity, and mineralized matrix formation in osteoblast cultures in three different phases of cell growth, in the presence and in the absence of titanium (Ti). Scanning electron microscopy (SEM), Raman spectra, and energy dispersive spectroscopy aided GO characterization. The presence of GO increased the viability of osteoblast cells grown on a plastic surface. However, osteoblast viability on Ti discs was lower in the presence than in the absence of GO. ALP activity emerged at 14 days for the cell culture incubated with GO. The total protein concentration also increased at 21 days on both the Ti discs and plastic surface. Osteoblasts grown on Ti discs had increased mineralized matrix formation in the presence of GO as compared to the cells grown in the absence of GO. SEM images of the cell cultures on plastic surfaces in the presence of GO suggested delayed mineralized matrix formation. In conclusion, applications requiring the presence of Ti, such as prostheses and implants, should benefit from the use of GO, which may increase mineralized nodule formation, stimulate biomineralization, and accelerate bone regeneration. PMID- 26886820 TI - Mechanical and thermal behaviour of an acrylic bone cement modified with a triblock copolymer. AB - The basic formulation of an acrylic bone cement has been modified by the addition of a block copolymer, Nanostrength((r)) (NS), in order to augment the mechanical properties and particularly the fracture toughness of the bone cement. Two grades of NS at different levels of loading, between 1 and 10 wt.%, have been used. Mechanical tests were conducted to study the behaviour of the modified cements; specific tests measured the bend, compression and fracture toughness properties. The failure mode of the fracture test specimens was analysed using scanning electron microscopy (SEM). The effect of NS addition on the thermal properties was also determined, and the polymerisation reaction using differential scanning calorimetry. It was observed that the addition of NS produced an improvement in the fracture toughness and ductility of the cement, which could have a positive contribution by reducing the premature fracture of the cement mantle. The residual monomer content was reduced when the NS was added. However this also produced an increase in the maximum temperature and the heat delivered during the polymerisation of the cement. PMID- 26886821 TI - Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs. AB - In this paper, an injectable micellar supramolecular hydrogel composed of alpha cyclodextrin (alpha-CD) and monomethoxy poly(ethylene glycol)-b-poly(epsilon caplactone) (MPEG5000-PCL5000) micelles was developed by a simple method for hydrophobic anticancer drug delivery. By mixing alpha-CD aqueous solution and MPEG5000-PCL5000 micelles, an injectable micellar supramolecular hydrogel could be formed under mild condition due to the inclusion complexation between alpha-CD and MPEG segment of MPEG5000-PCL5000 micelles. The resultant supramolecular hydrogel was thereafter characterized by X-ray diffraction (XRD) and Scanning electron microscopy (SEM). The effect of alpha-CD amount on the gelation time, mechanical strength and thixotropic property was studied by a rheometer. Payload of hydrophobic paclitaxel (PTX) to supramolecular hydrogel was achieved by encapsulation of PTX into MPEG5000-PCL5000 micelles prior mixing with alpha-CD aqueous solution. In vitro release study showed that the release behavior of PTX from hydrogel could be modulated by change the alpha-CD amount in hydrogel. Furthermore, such supramolecular hydrogel could enhance the biological activity of encapsulated PTX compared to free PTX, as indicated by in vitro cytotoxicity assay. All these results indicated that the developed micellar supramolecular hydrogel might be a promising injectable drug delivery system for anticancer therapy. PMID- 26886822 TI - Dynamic finite element simulation of the gunshot injury to the human forehead protected by polyvinyl alcohol sponge. AB - Although there are some traditional models of the gunshot wounds, there is still a need for more modeling analyses due to the difficulties related to the gunshot wounds to the forehead region of the human skull. In this study, the degree of damage as a consequence of penetrating head injuries due to gunshot wounds was determined using a preliminary finite element (FE) model of the human skull. In addition, the role of polyvinyl alcohol (PVA) sponge, which can be used as an alternative to reinforce the kinetic energy absorption capacity of bulletproof vest and helmet materials, to minimize the amount of skull injury due to penetrating processes was investigated through the FE model. Digital computed tomography along with magnetic resonance imaging data of the human head were employed to launch a three-dimensional (3D) FE model of the skull. Two geometrical shapes of projectiles (steel ball and bullet) were simulated for penetrating with an initial impact velocity of 734 m/s using nonlinear dynamic modeling code, namely LS-DYNA. The role of the damaged/distorted elements were removed during computation when the stress or strain reached their thresholds. The stress distributions in various parts of the forehead and sponge after injury were also computed. The results revealed the same amount of stress for both the steel ball and bullet after hitting the skull. The modeling results also indicated the time that steel ball takes to penetrate into the skull is lower than that of the bullet. In addition, more than 21% of the steel ball's kinetic energy was absorbed by the PVA sponge and, subsequently, injury sternness of the forehead was considerably minimized. The findings advise the application of the PVA sponge as a substitute strengthening material to be able to diminish the energy of impact as well as the load transmitted to the object. PMID- 26886823 TI - Phycocyanin-encapsulating hyalurosomes as carrier for skin delivery and protection from oxidative stress damage. AB - The phycobiliprotein phycocyanin, extracted from Klamath algae, possesses important biological properties but it is characterized by a low bioavailability due to its high molecular weight. To overcome the bioavailability problems, phycocyanin was successfully encapsulated, using an environmentally-friendly method, into hyalurosomes, a new kind of phospholipid vesicles immobilised with hyaluronan sodium salt by the simple addition of drug/sodium hyaluronate water dispersion to phospholipids. Liposomes were used as a comparison. Vesicles were small in size and homogeneously dispersed, being the mean size always smaller than 150 nm and PI never higher than 0.31. Liposomes were unilamellar and spherical, the addition of the polymer slightly modify the vesicular shape which remain spherical, while the addition of PEG improve the lamellarity of vesicles being multilamellar vesicles. In all cases phycocyanin was encapsulated in good amount especially using hyalurosomes and PEG hyalurosomes (65 and 61% respectively). In vitro penetration studies suggested that hyalurosomes favoured the phycocyanin deposition in the deeper skin layers probably thanks to their peculiar hyaluronan-phospholipid structure. Moreover, hyalurosomes were highly biocompatible and improved phycocyanin antioxidant activity on stressed human keratinocytes respect to the drug solution. PMID- 26886824 TI - Preparation and characterization of biomedical highly porous Ti-Nb alloy. AB - The compressive strength and the biocompatibility were assessed for the porous Ti 25 wt%Nb alloy fabricated by the combination of the sponge impregnation technique and sintering technique. The alloy provided pore sizes of 300-600 MUm, porosity levels of 71 +/- 1.5%, in which the volume fraction of open pores was 94 +/- 1.3%. The measurements also showed that the alloy had the compressive Young's modulus of 2.23 +/- 0.5 GPa and the strength of 98.4 +/- 4.5 MPa, indicating that the mechanical properties of the alloy are similar to those of human bone. The scanning electron microscopy (SEM) observations revealed that the pores were well connected to form three-dimension (3D) network open cell structure. Moreover, no obvious impurities were detected in the porous structure. The experiments also confirmed that rabbit bone mesenchymal stem cells (MSCs) could adhere and proliferate in the porous Ti-25 wt%Nb alloy. The interactions between the porous alloy and the cells are attributed to the porous structure with relatively higher surface. The suitable mechanical and biocompatible properties confirmed that this material has a promising potential in the application for tissue engineering. PMID- 26886825 TI - Aquated cisplatin and heparin-pluronic nanocomplexes exhibiting sustainable release of active platinum compound and NCI-H460 lung cancer cell antiproliferation. AB - In recent decades, platinum compounds have been many contributions in medicine. Development of new drugs from the active platinum compounds as well as nanocarriers for targeted delivery and reducing side effects of the drugs has paid much attention. In the study, nanocomplexes were prepared from aquated species of cisplatin and pluronic-conjugated heparin which distributed in the range of 80-100 nm by Transmission Electron Microscopy and 134 nm by Dynamic light scattering (DLS). Formation of the complex was confirmed by FTIR and DLS. The nanocomplexes exhibited high drug-loading capacity (approximately 42.5% wt/wt at 37 degrees C and 37.5% wt/wt at 25 degrees C). In vitro, drug-loaded nanogels showed much slower release profiles of cisplatin CDDP in pH 7.4 (physiological pH) compared with pH 5.5 condition at 37 degrees C. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, CDDP-loaded nanocomplex was able to reduce the cytotoxic ability of free CDDP (IC50 = 5.68 +/- 0.73 MUg/ml), which still maintain a significantly antiproliferative activity on NCI-H460 lung cancer cell. The in vitro preliminarily obtained results indicate that the nanocomplex is a candidate for CDDP delivery which can be studied further in cancer therapy. PMID- 26886826 TI - Over-the-counter medicine and dietary supplement consumption among academic youth in Poland. AB - Over-the-counter (OTC) medicines and dietary supplements are increasingly popular in Poland, potentially improving but also potentially posing a threat to public health. The study goal is to characterize and assess behaviors related to use of OTC medicines and dietary supplements among Polish university students. A questionnaire-based survey was performed with students divided into groups (gender, subjects studied, period of studies). The majority of students declared using the products, significantly more females and younger students in their early years. Females tended to be more attentive to product information. Students with a background in biological or medical sciences were also more attentive and less influenced by advertising. The authors present that the differences between the defined groups of students should be utilized in tailored educational activities, aiming to rationalize high consumption of OTC medicines and dietary supplements. Targeting other, especially low-socioeconomic and less-educated, groups should follow. PMID- 26886829 TI - Special Note from the Editor-in-Chief. PMID- 26886827 TI - Emotion-focused treatments for anorexia nervosa: a systematic review of the literature. AB - PURPOSE: The present review explores emotion-focused treatments for anorexia nervosa (AN). METHODS: We conducted a systematic literature search across key databases (PsychINFO, PubMed/Medline, and Web of Science) prior to September 2015. Twenty studies were selected for systematic review. RESULTS: The present review found initial evidence supporting the acceptability and feasibility of emotion-focused treatments for AN. Although preliminary results are promising, further controlled studies are necessary to establish the efficacy of emotion focused treatments for AN. CONCLUSIONS: Future controlled trials should compare emotion-focused treatments against each other and against other AN treatments. Future studies should also examine the mechanisms of action for the emotion focused treatments and treatment moderators. PMID- 26886828 TI - A convenient prognostic score consisting of the Glasgow prognostic score and serum lactate dehydrogenase predicts clinical outcome in patients with diffuse large B-cell lymphoma. PMID- 26886830 TI - Hopes, Promises, and Future Directions of Gene and Cell Therapies in France. PMID- 26886831 TI - Gene and Cell Therapies: Inserm at the Heart of Biomedical Revolutions. PMID- 26886833 TI - Transfer of the Cystic Fibrosis Transmembrane Conductance Regulator to Human Cystic Fibrosis Cells Mediated by Extracellular Vesicles. AB - Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in a deficiency in chloride channel activity. In this study, extracellular vesicles (EVs), microvesicles, and exosomes were used as vehicles to deliver exogenous CFTR glycoprotein and its encoding mRNA (mRNA(GFP-CFTR)) to CF cells to correct the CFTR chloride channel function. We isolated microvesicles and exosomes from the culture medium of CFTR-positive Calu-3 cells, or from A549 cells transduced with an adenoviral vector overexpressing a GFP-tagged CFTR (GFP-CFTR). Both microvesicles and exosomes had the capacity to package and deliver the GFP-CFTR glycoprotein and mRNA(GFP-CFTR) to target cells in a dose-dependent manner. Homologous versus heterologous EV-to-cell transfer was studied, and it appeared that the cellular uptake of EVs was significantly more efficient in homologous transfer. The incubation of CF15 cells, a nasal epithelial cell line homozygous for the DeltaF508 CFTR mutation, with microvesicles or exosomes loaded with GFP CFTR resulted in the correction of the CFTR function in CF cells in a dose dependent manner. A time-course analysis of EV-transduced CF cells suggested that CFTR transferred as mature glycoprotein was responsible for the CFTR-associated channel activity detected at early times posttransduction, whereas GFP-CFTR translated from exogenous mRNA(GFP-CFTR) was responsible for the CFTR function at later times. Collectively, this study showed the potential application of microvesicles and exosomes as vectors for CFTR transfer and functional correction of the genetic defect in human CF cells. PMID- 26886834 TI - "RCL-Pooling Assay": A Simplified Method for the Detection of Replication Competent Lentiviruses in Vector Batches Using Sequential Pooling. AB - Nonreplicative recombinant HIV-1-derived lentiviral vectors (LV) are increasingly used in gene therapy of various genetic diseases, infectious diseases, and cancer. Before they are used in humans, preparations of LV must undergo extensive quality control testing. In particular, testing of LV must demonstrate the absence of replication-competent lentiviruses (RCL) with suitable methods, on representative fractions of vector batches. Current methods based on cell culture are challenging because high titers of vector batches translate into high volumes of cell culture to be tested in RCL assays. As vector batch size and titers are continuously increasing because of the improvement of production and purification methods, it became necessary for us to modify the current RCL assay based on the detection of p24 in cultures of indicator cells. Here, we propose a practical optimization of this method using a pairwise pooling strategy enabling easier testing of higher vector inoculum volumes. These modifications significantly decrease material handling and operator time, leading to a cost-effective method, while maintaining optimal sensibility of the RCL testing. This optimized "RCL pooling assay" ameliorates the feasibility of the quality control of large-scale batches of clinical-grade LV while maintaining the same sensitivity. PMID- 26886835 TI - Gerontology across the professions and the Atlantic: Development and evaluation of an interprofessional and international course on aging and health. AB - The need for interprofessional teamwork and the global challenges for health care systems of dramatically increasing numbers of older adults have received increased recognition in gerontological and geriatrics education. The authors report on the pilot development of a hybrid course on aging and health for graduate-level health professions students from Norway, Canada, and the United States. International faculty from partnering universities developed, taught, and evaluated the course. Course assignments included online forum postings, reflections, and a problem-based learning group assignment and presentation. Directed readings and discussion included topics related to health care systems and services in the three participating countries, teamwork, and patient-centered care. To evaluate the course, quantitative and qualitative data were collected and analyzed. Results indicate a significant impact on student learning outcomes, including understanding of issues in international aging and health, attitudes and skills in teamwork, and application to clinical practice. This course clearly established the importance of developing innovative interprofessional educational experiences that respond to the increasingly universal impacts of aging populations on health and social care systems around the world. PMID- 26886832 TI - Gene Therapy of the beta-Hemoglobinopathies by Lentiviral Transfer of the beta(A(T87Q))-Globin Gene. AB - beta-globin gene disorders are the most prevalent inherited diseases worldwide and result from abnormal beta-globin synthesis or structure. Novel therapeutic approaches are being developed in an effort to move beyond palliative management. Gene therapy, by ex vivo lentiviral transfer of a therapeutic beta-globin gene derivative (beta(AT87Q)-globin) to hematopoietic stem cells, driven by cis regulatory elements that confer high, erythroid-specific expression, has been evaluated in human clinical trials over the past 8 years. beta(AT87Q)-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker. While long-term studies are underway in multiple centers in Europe and in the United States, proof-of-principle of efficacy and safety has already been obtained in multiple patients with beta-thalassemia and sickle cell disease. PMID- 26886836 TI - Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo. AB - Arsenic trioxide (As2O3) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (omega) 3 fatty acid on As2O3-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with As2O3 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. As2O3 significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S transferase, superoxide dismutase and catalase in heart tissue of arsenic administered rats. The cardioprotective role of omega-3 fatty acid was assessed by combination treatment with As2O3. omega-3 fatty acid co-administration with As2O3 significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, As2O3 treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (?Psim). omega-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ?Psim. These findings suggested that the omega-3 fatty acid has the potential to protect against As2O3-induced cardiotoxicity. PMID- 26886840 TI - FLT3 Inhibitor-Associated Neutrophilic Dermatoses. PMID- 26886841 TI - Juvenile dermatomyositis: A report of three cases. AB - Juvenile dermatomyositis (JDM), an autoimmune idiopathic myositis, is characterized by rash and proximal muscle weakness. Immunohistopathology typically shows perivascular inflammatory infiltrate with predominance of CD4+ T lymphocytes, perifascicular atrophy, and upregulation of major histocompatibility complex class I. JDM has been attributed to a humoral-driven muscle microangiopathy probably implicating the type I interferon pathway. Tubulo reticular inclusions present in endothelial cell of muscle are biomarkers of interferon exposure, and so may be an indirect data of this myopathy especially in the absence of rash and inflammatory infiltrate. We report on three patients in which electron microscopy solves the differential diagnosis among infantile myositis showing peculiar inclusions. PMID- 26886842 TI - Assessment of Total Choline Intakes in the United States. AB - OBJECTIVE: Choline is an essential nutrient and plays a critical role in brain development, cell signaling, nerve impulse transmission, and lipid transport and metabolism. This analysis aimed to assess usual intakes of choline and compare them with the dietary reference intakes for U.S. residents aged >= 2 years. METHODS: The National Cancer Institute method was used to assess usual intakes of choline from foods according to data for participants in the 2009-2012 National Health and Nutrition Examination Survey (NHANES; n = 16,809). RESULTS: Suboptimal intakes of choline are prevalent across many life-stage subpopulations in the United States. Only 10.8 +/- 0.6% of 2009-2012 NHANES participants aged >= 2 years (15.6 +/- 0.8% of males and 6.1 +/- 0.6% of females) achieved the adequate intake (AI) for choline. Children aged 2-3 years were the most likely to exceed the AI (62.9 +/- 3.1%), followed by children aged 4-8 years (45.4 +/- 1.6%) and children aged 9-13 years (9.0 +/- 1.0%), compared to adolescents aged 14-18 years (1.8 +/- 0.4%) and adults aged >= 19 years (6.6 +/- 0.5%). When comparing by age and gender, males consumed significantly more choline than females for all age groups. CONCLUSIONS: These data indicate that there is a need to increase awareness among health professionals and consumers regarding potential suboptimal intakes of choline in the United States, as well as the critical role that choline plays in health maintenance throughout the lifespan. Food scientists and the food and dietary supplement industries should consider working collectively with government agencies to discuss strategies to help offset the percentage of the population that does not meet the AI. Revision of the dietary reference intakes for choline should include replacement of the AI with an estimated average requirement and a recommended dietary allowance, so that more accurate population estimates of inadequate intakes may be calculated. PMID- 26886843 TI - Prevalence and Characterization of Cronobacter sakazakii in Retail Milk-Based Infant and Baby Foods in Shaanxi, China. AB - Cronobacter sakazakii (formerly Enterobacter sakazakii) is an opportunistic pathogen that causes meningitis, sepsis, and necrotizing enterocolitis in neonates and infants through consumption of contaminated milk-based foods. In this study, the prevalence of C. sakazakii in 705 retail milk-based infant and baby food samples was investigated in 12 cities in Shaanxi, China, in 2010 and 2012. One hundred and nineteen samples (16.9%) were C. sakazakii positive. The isolates were further characterized for antimicrobial susceptibility to 14 antibiotics, pulsed-field gel electrophoresis profiles, and presence of the virulence genes. Samples of brand W, Y, A, and G in 2010 and 2012 were C. sakazakii positive. All isolates recovered in 2010 and 2012 were susceptible to levofloxacin and cefoperazone. In 2012, no isolate was resistant to gentamicin, cefoxitin, chloramphenicol, gatifloxacin, ciprofloxacin, and ceftriaxone. Antibiotic resistance of the isolates was most commonly found to rifampicin, amoxicillin-clavulanic acid, streptomycin, tetracycline, and ampicillin in both 2010 and 2012, except to trimethoprim/sulfamethoxazole in 2012. Pulsed-field gel electrophoresis profiles indicated that C. sakazakii isolates were genotypically diverse, although these isolates were prevalent in infant and baby foods with the same brand. A total of 34 virulence gene profiles of the C. sakazakii isolates in 2010 and 2012 were detected. Isolates that co-carried hly-ompX-eitCBAD iucABCD/iutA genes in 2012 were significantly (p < 0.05) more prevalent than those in 2010. The results added new epidemiological evidence for the widespread occurrence of C. sakazakii in retail milk-based infant and baby foods and this should be an indicator of potential health risk for consumers. PMID- 26886844 TI - Genetic variants in MiR-29a associated with high myopia. PMID- 26886845 TI - Label-Free Real-Time Microarray Imaging of Cancer Protein-Protein Interactions and Their Inhibition by Small Molecules. AB - A rapid optical microarray imaging approach for anticancer drug screening at specific cancer protein-protein interface targets with binding kinetics and validation by a mass sensor is reported for the first time. Surface plasmon resonance imager (SPRi) demonstrated a 3.5-fold greater specificity for interactions between murine double minute 2 protein (MDM2) and wild-type p53 over a nonspecific p53 mutant in a real-time microfluidic analysis. Significant percentage reflectivity changes (Delta%R) in the SPRi signals and molecular-level mass changes were detected for both the MDM2-p53 interaction and its inhibition by a small-molecule Nutlin-3 drug analogue known for its anticancer property. We additionally demonstrate that synthetic, inexpensive binding domains of interacting cancer proteins are sufficient to screen anticancer drugs by an array based SPRi technique with excellent specificity and sensitivity. This imaging array, combined with a mass sensor, can be used to study quantitatively any protein-protein interaction and screen for small molecules with binding and potency evaluations. PMID- 26886848 TI - Differences between the insulating limit quasiparticles of one-band and three band cuprate models. AB - We study the charge dynamics of the quasiparticle that forms when a single hole is doped in a two-dimensional antiferromagnet as described by the one-band t-t' t"-J model, using a variational approximation that includes spin fluctuations in the vicinity of the hole. We explain why the spin fluctuations and the longer range hopping have complementary contributions to the quasiparticle dynamics, and thus why both are essential to obtain a dispersion in agreement with that measured experimentally. This is very different from the three-band Emery model in the strongly-correlated limit, where the same variational approximation shows that spin fluctuations have a minor effect on the quasiparticle dynamics. This difference proves that these one-band and three-band models describe qualitatively different quasiparticles in the insulating limit, and therefore that they cannot both be suitable to describe the physics of very underdoped cuprates. PMID- 26886847 TI - Rheumatoid arthritis patients undergoing total hip and knee arthroplasty have better in-hospital outcomes compared with non-rheumatoid arthritis patients. AB - OBJECTIVES: Rheumatoid arthritis (RA) is known to be associated with multiple comorbidities and, therefore, overall management is critical for those patients undergoing elective major orthopaedic surgeries, such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to compare in-hospital outcomes of elective THA and TKA between patients with and without RA in the US during the last decade. We hypothesised that patients with RA would have similar perioperative outcomes after elective THA and TKA. METHODS: Clinical data were derived from the US Nationwide Inpatient Sample (NIS) between 2000 and 2009. Patients who underwent elective THA and TKA were identified. Data regarding patient- and healthcare system-related characteristics, comorbidities, in hospital complications, and mortality were retrieved. In-hospital outcomes of the procedures were compared between patients with and without RA. RESULTS: Comparison between patients with and without RA showed that patients with RA had significantly lower overall in-hospital complication rates following THA and TKA, and lower in-hospital mortality rate following THA. Patients with RA undergoing THA and TKA had decreased risk of overall in-hospital complications compared to those without RA. CONCLUSIONS: Contrary to our hypothesis, perioperative outcomes of elective THA and TKA in patients with RA were better than those in patients without RA. These results may indicate that patient selection and pre- and perioperative management of patients with RA undergoing elective THA and TKA were well conducted in the US during the last decade. PMID- 26886846 TI - Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa. AB - Response to the 2014-2015 Ebola outbreak in West Africa overwhelmed the healthcare systems of Guinea, Liberia, and Sierra Leone, reducing access to health services for diagnosis and treatment for the major diseases that are endemic to the region: malaria, HIV/AIDS, and tuberculosis. To estimate the repercussions of the Ebola outbreak on the populations at risk for these diseases, we developed computational models for disease transmission and infection progression. We estimated that a 50% reduction in access to healthcare services during the Ebola outbreak exacerbated malaria, HIV/AIDS, and tuberculosis mortality rates by additional death counts of 6,269 (2,564-12,407) in Guinea; 1,535 (522-2,8780) in Liberia; and 2,819 (844-4,844) in Sierra Leone. The 2014-2015 Ebola outbreak was catastrophic in these countries, and its indirect impact of increasing the mortality rates of other diseases was also substantial. PMID- 26886849 TI - Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode. AB - Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (KC = 14.3 nM) and also of hBChE (KC = 19.7 nM). The inhibitors transfer the carbamate moiety onto the active site under release of the phenolic tetrahydroquinazoline scaffolds that themselves act as neuroprotectants. By combination of kinetic data with molecular docking studies, a plausible binding model was probed describing how the tetrahydroquinazoline scaffold guides the carbamate into a close position to the active site. The model explains the influence of the carrier scaffold onto the affinity of an inhibitor just before carbamate transfer. This strategy can be used to utilize the binding mode of other carbamate-based inhibitors. PMID- 26886850 TI - Molecular Characterization of the Gas-Particle Interface of Soot Sampled from a Diesel Engine Using a Titration Method. AB - Surface functional groups of two different types of combustion aerosols, a conventional diesel (EN 590) and a hydrotreated vegetable oil (HVO) soot, have been investigated using heterogeneous chemistry (i.e., gas-particle surface reactions). A commercial sample of amorphous carbon (Printex XE2-B) was analyzed as a reference substrate. A Knudsen flow reactor was used to carry out the experiments under molecular flow conditions. The selected gases for the titration experiments were: N(CH3)3 for the identification of acidic sites, NH2OH for the presence of carbonyl groups, CF3COOH and HCl for basic sites of different strength, and O3 and NO2 for reducing groups. Reactivity with N(CH3)3 indicates a lower density of acidic functionalities for Printex XE2-B in relation to diesel and HVO soot. Results for NH2OH experiments indicates that commercial amorphous carbon exhibits a lower abundance of available carbonyl groups at the interface compared to the results from diesel and HVO soot, the latter being the one with the largest abundance of carbonyl functions. Reactions with acids indicate the presence of weak basic oxides on the particle surface that preferentially interact with the strong acid CF3COOH. Finally, reactions with O3 and NO2 reveal that diesel and especially HVO have a significantly higher reactivity with both oxidizers compared to that of Printex XE2-B because they have more reducing sites by roughly a factor of 10 and 30, respectively. The kinetics of titration reactions have also been investigated. PMID- 26886851 TI - Parental Perception of Weight Status: Influence on Children's Diet in the Gateshead Millennium Study. AB - OBJECTIVE: Recognising overweight and obesity is critical to prompting action, and consequently preventing and treating obesity. The present study examined the association between parental perceptions of child weight status and child's diet. METHODS: Participants were members of the Gateshead Millennium Study. Parental perception of their child's weight status was assessed using a questionnaire and compared against International Obesity Task Force cut-offs for childhood overweight and obesity when the children were aged 6-8 years old. Diet was assessed at age 6-8years old using the FAST (Food Assessment in Schools Tool) food diary method. The association between parental perception and dietary patterns as defined by Principal Components Analysis, was assessed using multivariate regression after adjustment for child's gender, child's weight status, maternal body mass index (BMI), maternal education and deprivation status. RESULTS: Of the 361 parents who provided complete data on confounders and on their perception of their child's weight status, 63 (17%) parents perceived their child as being of 'normal' weight or 'overweight' when they were actually 'overweight' or 'obese', respectively. After adjustment for confounders, parents who misperceived their child's weight had children with a lower 'healthy' dietary pattern score compared to children whose parents correctly perceived their weight (beta = -0.88; 95% CI: -1.7, -0.1; P-value = 0.028). This association was found despite higher consumption of reduced sugar carbonated drinks amongst children whose parents incorrectly perceived their weight status compared to children whose parents perceived their weight correctly (52.4% vs. 33.6%; P-value = 0.005). CONCLUSIONS: In conclusion, children whose parents did not correctly perceive their weight status scored lower on the 'healthy' dietary pattern. Further research is required to define parents' diets based on their perception status and to examine if a child's or parent's diet mediates the association between parental perception and child weight. PMID- 26886852 TI - Comprehensive Expression Profiling and Functional Network Analysis of p53 Regulated MicroRNAs in HepG2 Cells Treated with Doxorubicin. AB - Acting as a sequence-specific transcription factor, p53 tumor suppressor involves in a variety of biological processes after being activated by cellular stresses such as DNA damage. In recent years, microRNAs (miRNAs) have been confirmed to be regulated by p53 in several cancer types. However, it is still unclear how miRNAs orchestrate their regulation and function in p53 network after p53 activation in hepatocellular carcinoma (HCC). In this study, we used small RNA sequencing and systematic bioinformatic analysis to characterize the regulatory networks of differentially expressed miRNAs after the p53 activation in HepG2. Here, 33 miRNAs significantly regulated by p53 (12 up-regulated and 21 down-regulated) were detected between the doxorubicin-treated and untreated HepG2 cells in two biological replicates for small RNA sequencing and 8 miRNAs have been reported previously to be associated with HCC. Gene ontology (GO) and KEGG pathway enrichment analysis showed that 87.9% (29 out of 33) and 90.9% (30 out of 33) p53 regulated miRNAs were involved in p53-related biological processes and pathways with significantly low p-value, respectively. Remarkably, 18 out of 33 p53 regulated miRNAs were identified to contain p53 binding sites around their transcription start sites (TSSs). Finally, comprehensive p53-miRNA regulatory networks were constructed and analyzed. These observations provide a new insight into p53-miRNA co-regulatory network in the context of HCC. PMID- 26886853 TI - Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort. AB - BACKGROUND: Toxoplasma gondii (T. gondii) is a protozoan parasite present in around a third of the human population. Infected individuals are commonly asymptomatic, though recent reports have suggested that infection might influence aspects of the host's behavior. In particular, Toxoplasma infection has been linked to schizophrenia, suicide attempt, differences in aspects of personality and poorer neurocognitive performance. However, these studies are often conducted in clinical samples or convenience samples. METHODS/RESULTS: In a population representative birth-cohort of individuals tested for presence of antibodies to T. gondii (N = 837) we investigated the association between infection and four facets of human behavior: neuropsychiatric disorder (schizophrenia and major depression), poor impulse control (suicidal behavior and criminality), personality, and neurocognitive performance. Suicide attempt was marginally more frequent among individuals with T. gondii seropositivity (p = .06). Seropositive individuals also performed worse on one out of 14 measures of neuropsychological function. CONCLUSION: On the whole, there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment. PMID- 26886856 TI - Why Dyes Should Not Be Used to Test the Photocatalytic Activity of Semiconductor Oxides. PMID- 26886854 TI - The Formation of Microthrombi in Parenchymal Microvessels after Traumatic Brain Injury Is Independent of Coagulation Factor XI. AB - Microthrombus formation and bleeding worsen the outcome after traumatic brain injury (TBI). The aim of the current study was to characterize these processes in the brain parenchyma after experimental TBI and to determine the involvement of coagulation factor XI (FXI). C57BL/6 mice (n = 101) and FXI-deficient mice (n = 15) were subjected to controlled cortical impact (CCI). Wild-type mice received an inhibitory antibody against FXI (14E11) or control immunoglobulin G 24 h before or 30 or 120 min after CCI. Cerebral microcirculation was visualized in vivo by 2-photon microscopy 2-3 h post-trauma and histopathological outcome was assessed after 24 h. TBI induced hemorrhage and microthrombus formation in the brain parenchyma (p < 0.001). Inhibition of FXI activation or FXI deficiency did not reduce cerebral thrombogenesis, lesion volume, or hemispheric swelling. However, it also did not increase intracranial hemorrhage. Formation of microthrombosis in the brain parenchyma after TBI is independent of the intrinsic coagulation cascade since it was not reduced by inhibition of FXI. However, since targeting FXI has well-established antithrombotic effects in humans and experimental animals, inhibition of FXI could represent a reasonable strategy for the prevention of deep venous thrombosis in immobilized patients with TBI. PMID- 26886855 TI - The Association Between Body Mass Index and Presenting Symptoms in African American Women with Ovarian Cancer. AB - BACKGROUND: Ovarian cancer, the most lethal gynecologic malignancy, typically comes to clinical attention due to nonspecific gastrointestinal or pelvic symptoms. African Americans with ovarian cancer have a greater mortality burden than whites and are also much more likely to be obese. The objective of this study is to explore whether the presentation and duration of symptoms differ by body mass index (BMI) in African Americans with ovarian cancer. METHODS: We conducted a case-only analysis using data from a multicenter population-based study of invasive epithelial ovarian cancer in African American women. Information on risk factors and symptoms leading to diagnosis was obtained in a telephone interview. Frequency and duration of symptoms by BMI categories were compared using logistic regression and linear regression analyses. RESULTS: Of the 326 women, ~60% was obese (BMI >=30), with 30.8% having a BMI >=35 kg/m(2). Ninety-four percent of women reported >=1 symptom during the year before diagnosis. We observed differences in frequency of symptoms by BMI categories, with most being reported more frequently by the heaviest women. The reported duration of symptoms was longer in women with higher BMI, with statistically significant trend tests for 6 of the 10 symptoms evaluated. CONCLUSION: BMI appears to impact ovarian cancer symptomatology. Women with higher BMI report having symptoms for a longer period of time before diagnosis of ovarian cancer. Healthcare providers should be vigilant and consider ovarian cancer in the differential diagnosis for obese women presenting with abdominal and pelvic symptoms. PMID- 26886857 TI - Parameter Estimation in Stratified Cluster Sampling under Randomized Response Models for Sensitive Question Survey. AB - Randomized response is a research method to get accurate answers to sensitive questions in structured sample survey. Simple random sampling is widely used in surveys of sensitive questions but hard to apply on large targeted populations. On the other side, more sophisticated sampling regimes and corresponding formulas are seldom employed to sensitive question surveys. In this work, we developed a series of formulas for parameter estimation in cluster sampling and stratified cluster sampling under two kinds of randomized response models by using classic sampling theories and total probability formulas. The performances of the sampling methods and formulas in the survey of premarital sex and cheating on exams at Soochow University were also provided. The reliability of the survey methods and formulas for sensitive question survey was found to be high. PMID- 26886858 TI - Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats. AB - The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg.kg( 1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves).kg(-1).day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis. PMID- 26886859 TI - Pseudo-De Novo Assembly and Analysis of Unmapped Genome Sequence Reads in Wild Zebrafish Reveal Novel Gene Content. AB - Zebrafish represents the third vertebrate with an officially completed genome, yet it remains incomplete with additions and corrections continuing with the current release, GRCz10, having 13% of zebrafish cDNA sequences unmapped. This disparity may result from population differences, given that the genome reference was generated from clonal individuals with limited genetic diversity. This is supported by the recent analysis of a single wild zebrafish, which identified over 5.2 million SNPs and 1.6 million in/dels in the previous genome build, zv9. Re-examination of this sequence data set indicated that 13.8% of quality sequence reads failed to align to GRCz10. Using a novel bioinformatics de novo assembly pipeline on these unmappable reads, we identified 1,514,491 novel contigs covering ~224 Mb of genomic sequence. Among these, 1083 contigs were found to contain a potential gene coding sequence. RNA-seq data comparison confirmed that 362 contigs contained a transcribed DNA sequence, suggesting that a large amount of functional genomic sequence remains unannotated in the zebrafish reference genome. By utilizing the bioinformatics pipeline developed in this study, the zebrafish genome will be bolstered as a model for human disease research. Adaptation of the pipeline described here also offers a cost-efficient and effective method to identify and map novel genetic content across any genome and will ultimately aid in the completion of additional genomes for a broad range of species. PMID- 26886861 TI - Brain herniations into arachnoid granulations: about 68 cases in 38 patients and review of the literature. AB - INTRODUCTION: Brain herniations (BH) into arachnoid granulations (AG) in dural venous sinuses and calvarium have rarely been reported in the literature. METHODS: MRIs of 38 patients with BH into AG (BHAG) were retrospectively analyzed. Locations of BHAG, gyrus/lobe of the herniated brain, parenchymal abnormalities of the BH, and clinical and radiological conditions with raised intracranial pressure were recorded. RESULTS: Sixty-eight BHAG were found, by order of frequency, in the occipital squama (OS), transverse sinus (TS), lateral lacuna of the superior sagittal sinus (LLSSS), and straight sinus (SS), with cerebellar tissue being the most frequently involved in BHAG (94.5 % of OS, 55 % of TS, 100 % SS BHAG). Multiple BHAG were found in 58 % of the patients (up to five per patient). Parenchymal signal and structural changes (SSCG) were observed in 46 % of BHAG (100 % were cerebellar). Three patients had pseudotumor cerebri (PTCS); one patient had only MRI signs of PTCS. Twenty-one percent of patients had intracranial conditions susceptible of increasing cerebrospinal fluid (CSF) pressure other than PTCS. CONCLUSIONS: BHAG occurred in the OS, TS, LLSSS, and the SS. SSCG of the herniated cerebellum were frequent and possibly result from tethering/strangulation in the AG. No symptoms could be clearly attributed to BHAG, though in three cases of PTCS, TS BHAG could have contributed to sustaining the raised CSF pressure. Various factors are probably involved in the development of BHAG including normal pia-arachnoid bridges between the brain surface and the AG, hydrodynamic constrains on the brain and AG, and, in some cases, increased intracranial pressure. PMID- 26886862 TI - Neuroanesthesiology Update. AB - We provide a synopsis of innovative research, recurring themes, and novel experimental findings pertinent to the care of neurosurgical patients and critically ill patients with neurological diseases. The following broad topics are covered: general neurosurgery, spine surgery, stroke, traumatic brain injury, anesthetic neurotoxicity, perioperative cognitive dysfunction, and monitoring. PMID- 26886863 TI - Large-volume Epidural Blood Patch: An Alternative Technique. PMID- 26886864 TI - Preservation of Supported Lipid Membrane Integrity from Thermal Disruption: Osmotic Effect. AB - Preservation of structural integrity under various environmental conditions is one major concern in the development of the supported lipid membrane (SLM)-based devices. It is common for SLMs to experience temperature shifts from manufacture, processing, storage, and transport to operation. In this work, we studied the thermal adaption of the supported membranes on silica substrates. Homogenous SLMs with little defects were formed through the vesicle fusion method. The mass and fluidity of the bilayers were found to deteriorate from a heating process but not a cooling process. Fluorescence characterizations showed that the membranes initially budded as a result of heating-induced lipid lateral area expansion, followed by the possible fates including maintenance, retraction, and fission, among which the last contributes to the irreversible compromise of the SLM integrity and spontaneous release of the interlipid stress accumulated. Based on the mechanism, we developed a strategy to protect SLMs from thermal disruption by increasing the solute concentration in medium. An improved preservation of the membrane mass and fluidity against the heating process was observed, accompanied by a decrease in the retraction and fission of the buds. Theoretical analysis revealed a high osmotic energy penalty for the fission, which accounts for the depressed disruption. This osmotic-based protection strategy is facile, solute nonspecific, and long-term efficient and has little impact on the original SLM properties. The results may help broaden SLM applications and sustain the robustness of SLM-based devices under multiple thermal conditions. PMID- 26886865 TI - Stereoselective Total Synthesis of Atractylodemayne A, a Conjugated 2(E),8(Z),10(E)-Triene-4,6-diyne. AB - The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence. PMID- 26886866 TI - New Analytical Tool for the Detection of Ractopamine Abuse in Goat Skeletal Muscle by Potential Gene Expression Biomarkers. AB - In this study, quantification of mRNA gene expression was examined as biomarkers to detect ractopamaine abuse and ractopamaine residues in cashmere goats. It was focused on the identification of potential gene expression biomarkers and describing the coreletionship between gene expression and residue level by 58 animals for 49 days. The results showed that administration periods and residue levels significantly influenced mRNA expressions of the beta2-adrenergic receptor (beta2AR), the enzymes PRKACB, ADCY3, ATP1A3, ATP2A3, PTH, and MYLK, and the immune factors IL-1beta and TNF-alpha. Statistical analysis like principal components analysis (PCA), hierarchical cluster analysis (HCA), and discriminant analysis (DA) showed that these genes can serve as potential biomarkers for ractopamine in skeletal muscle and that they are also suitable for describing different residue levels separately. PMID- 26886869 TI - Zr-based metal-organic frameworks: design, synthesis, structure, and applications. AB - Among the large family of metal-organic frameworks (MOFs), Zr-based MOFs, which exhibit rich structure types, outstanding stability, intriguing properties and functions, are foreseen as one of the most promising MOF materials for practical applications. Although this specific type of MOF is still in its early stage of development, significant progress has been made in recent years. Herein, advances in Zr-MOFs since 2008 are summarized and reviewed from three aspects: design and synthesis, structure, and applications. Four synthesis strategies implemented in building and/or modifying Zr-MOFs as well as their scale-up preparation under green and industrially feasible conditions are illustrated first. Zr-MOFs with various structural types are then classified and discussed in terms of different Zr-based secondary building units and organic ligands. Finally, applications of Zr-MOFs in catalysis, molecule adsorption and separation, drug delivery, and fluorescence sensing, and as porous carriers are highlighted. Such a review based on a specific type of MOF is expected to provide guidance for the in-depth investigation of MOFs towards practical applications. PMID- 26886868 TI - An Analysis of Sponsors/Collaborators of 69,160 Drug Trials Registered with ClinicalTrials.gov. AB - BACKGROUND: Clinical trials have been criticized on various counts. Any attempt to improve how trials are conducted or reported requires--amongst other things- an understanding of the number, the nature and the location of those that sponsor them or collaborate on them. Here we sought to identify the nature and location of each sponsor/collaborator. METHODS AND FINDINGS: We examined the 'sponsor/collaborator' field for the 69,160 drug trials that were registered with ClinicalTrials.gov over a 9-year period (2005-2014). Of the 12,823 unique sponsors, 56% had sponsored only one and 27% had sponsored 2-5 trials each. Just 18% were involved with six or more trials each, and we have (arbitrarily) labeled these organizations as 'more experienced' in sponsoring/collaborating on trials. These 18% (2,266 sponsors/collaborators) were analyzed further: (a) 951 were corporate organizations and (b) 1,145 were non-corporates (including 31 individuals) with (c) 170 unclassified. Further, we identified the location of each organization in (a) and (b). CONCLUSIONS: Clinical trials are an important part of a nation's research endeavors, and ultimately contribute to the health of its people. Thus, understanding the clinical trial landscape--including the number and nature of sponsors, and how active they are--is important for every country. We believe that policy makers in particular should be interested in this study to understand the current situation, and to use the numbers as a baseline for the evolving landscape, to assess the impact of their strategies in future. PMID- 26886867 TI - Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry-Associated Membrane Antigen. AB - Rhoptry-associated membrane antigen (RAMA) is an abundant glycophosphatidylinositol (GPI)-anchored protein that is embedded within the lipid bilayer and is implicated in parasite invasion. Antibody responses against rhoptry proteins are produced by individuals living in a malaria-endemic area, suggesting the immunogenicity of Plasmodium vivax RAMA (PvRAMA) for induction of immune responses during P. vivax infection. To determine whether PvRAMA contributes to the acquisition of immunity to malaria and could be a rational candidate for a vaccine, the presence of memory T cells and the stability of the antibody response against PvRAMA were evaluated in P. vivax-exposed individuals. The immunogenicity of PvRAMA for the induction of T cell responses was evaluated by in vitro stimulation of peripheral blood mononuclear cells (PBMCs). High levels of interferon (IFN)-gamma and interleukin (IL)-10 cytokines were detected in the culture supernatant of PBMCs, and the CD4+ T cells predominantly produced IL-10 cytokine. The levels of total anti-PvRAMA immunoglobulin G (IgG) antibody were significantly elevated, and these antibodies persisted over the 12 months of the study. Interestingly, IgG1, IgG2 and IgG3 were the major antibody subtypes in the response to PvRAMA. The frequency of IgG3 in specific to PvRAMA antigen maintained over 12 months. These data could explain the immunogenicity of PvRAMA antigen in induction of both cell-mediated and antibody-mediated immunity in natural P. vivax infection, in which IFN-gamma helps antibody class switching toward the IgG1, IgG2 and IgG3 isotypes and IL-10 supports PvRAMA-specific antibody production. PMID- 26886870 TI - Metal-Insulator-Semiconductor Diode Consisting of Two-Dimensional Nanomaterials. AB - We present a novel metal-insulator-semiconductor (MIS) diode consisting of graphene, hexagonal BN, and monolayer MoS2 for application in ultrathin nanoelectronics. The MIS heterojunction structure was fabricated by vertically stacking layered materials using a simple wet chemical transfer method. The stacking of each layer was confirmed by confocal scanning Raman spectroscopy and device performance was evaluated using current versus voltage (I-V) and photocurrent measurements. We clearly observed better current rectification and much higher current flow in the MIS diode than in the p-n junction and the metal semiconductor diodes made of layered materials. The I-V characteristic curve of the MIS diode indicates that current flows mainly across interfaces as a result of carrier tunneling. Moreover, we observed considerably high photocurrent from the MIS diode under visible light illumination. PMID- 26886871 TI - Motivational Interviewing and the Transtheoretical Model of Change: Under Explored Resources for Suicide Intervention. AB - Motivational interviewing (MI) is a robust evidence-based intervention that has been used to evoke intrinsic motivation to change behaviors. MI as an intervention focuses on facilitating movement through the stages of the transtheoretical model of change. A study by Coombs et al. (Substance abuse treatment and the stages of change: Selecting and planning interventions, Guilford Press, New York, 2001) demonstrated that suicidal individuals move through such stages toward suicidal behavior, yet research and applications of MI for suicide have been minimal. In hopes of generating increased exploration of MI for suicidality, this article reviews the theoretical rationale and existing empirical research on applications of MI with suicidal individuals. Potential uses of MI in suicide risk assessment/crisis intervention, as well as an adjunct to longer-term treatment, are discussed. PMID- 26886872 TI - Topographical variations in zonal properties of canine tibial articular cartilage due to early osteoarthritis: a study using 7-T magnetic resonance imaging at microscopic resolution. AB - OBJECTIVE: Our aim was to determine topographical variations in zonal properties of articular cartilage over the medial tibia in an experimental osteoarthritis (OA) model using 7-T magnetic resonance imaging (MRI). MATERIALS AND METHODS: An anterior cruciate ligament (ACL)-transection canine model was subjected to study at 8 (six) and 12 (seven) weeks after the surgery. Each medial tibia was divided into five topographical locations. For each specimen, T2 relaxation (at 0 degrees and 55 degrees ) was quantified at microscopic resolution. The imaging data grouped the five locations into two topographical areas (meniscus-covered and uncovered). RESULTS: The T2 (55 degrees ) bulk values from the meniscus-covered area were significantly lower than those from the uncovered area. The total cartilage thicknesses on the meniscus-covered area were significantly thinner than those on the meniscus-uncovered area. Significant differences in the T2 (0 degrees ) values were observed in most thicknesses of the four subtissue zones and whole-tissue from the uncovered area, while the same significant changes were detected in the superficial zone from the meniscus-covered area. CONCLUSION: By quantifying high-resolution imaging data both topographically and depth dependently (zonal-wise), this study demonstrates that the rate of disease progression varies topographically over the medial tibia. Future correlation with OA pathology could lead to better detection of early OA. PMID- 26886873 TI - New Patient-Oriented Tools for Assessing Atrophic Acne Scarring. AB - INTRODUCTION: Scarring on visible areas such as the face is associated with negative psychological impact. Many patients with acne have clinically relevant scarring for which they seek treatment, implying that there is an impact on their lives. Currently there are no validated tools to assess the burden of atrophic acne scarring from the patient's perspective or to assess treatment benefit. METHODS: Two patient-reported outcome measures, the self-assessment of clinical acne-related scars (SCARS) and the facial acne scar quality of life (FASQoL) tools, both specific to facial atrophic acne scarring, were developed according to Food and Drug Administration guidance methodology. Patient interviews were conducted first to elicit patient-important concepts about scarring, then to validate patients' understanding of wording in the tools. These tools focus on symptoms (SCARS) and psychological and social well-being (FASQoL) and were designed to be suitable for self-completion and to be rapidly completed (2-5 min) within a clinical research setting. RESULTS: Concept elicitation interviews were conducted with 30 subjects and cognitive interviews with 20 subjects. With acne scarring, important concepts for patients included size, surface area affected, counts, and depth. The SCARS and FASQoL tools were shown to address relevant concepts that were easily understood by patients. CONCLUSION: Two patient reported measures, SCARS and FASQoL, have been developed to help clinicians assess the severity and impact of acne scars. Responsivity of these instruments to treatment will require further evaluation. FUNDING: Galderma R&D, Sophia Antipolis, France. PMID- 26886875 TI - Psychiatric Symptoms Associated with Oocyte-Donation. AB - Oocyte-donation is generally safe but may exacerbate psychiatric symptoms in some women. In this prospective study 63 oocyte-donating women and, as a control group, 63 women providing their own oocytes for in vitro fertilization (in couples with male infertility) were evaluated pre- and post-ovulation-induction in regard to hypochondriasis, anxiety, social impairment, and depression. The mean hypochondriasis score for oocyte-donators was significantly lower than for women providing their own oocytes, prior to ovulation-induction (5.03 vs. 6.59). However, after ovulation-induction and oocyte retrieval this score rose to 6.66 among oocyte-donators, whereas it remained essentially unchanged among women providing their own oocytes (6.66). The mean anxiety score for oocyte-donating women also rose following this procedure, from 5.87 to 7.65. Depression scores for both groups remained similar, before and after the procedure. Results showed that at the beginning of the ARP donating women have the same conditions as own oocyte women regarding depression and anxiety but after the egg harvesting they would suffer more damages regarding hypochondriasis and anxiety aspects. PMID- 26886874 TI - A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine. AB - OBJECTIVE: To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-alpha and nuclear factor kappa B (NF-kappaB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. METHODS: The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media--iohexol 10 ml kg( 1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. RESULTS: Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-alpha, NF-kappaB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. CONCLUSION: Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-kappaB, TNF-alpha and IL-6). ADVANCES IN KNOWLEDGE: CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats. PMID- 26886876 TI - Net Effects of Ecotourism on Threatened Species Survival. AB - Many threatened species rely on ecotourism for conservation funding, but simultaneously suffer direct ecological impacts from ecotourism. For a range of IUCN-Redlisted terrestrial and marine bird and mammal species worldwide, we use population viability analyses to calculate the net effects of ecotourism on expected time to extinction, in the presence of other anthropogenic threats such as poaching, primary industries and habitat loss. Species for which these calculations are currently possible, for one or more subpopulations, include: orangutan, hoolock gibbon, golden lion tamarin, cheetah, African wild dog, New Zealand sealion, great green macaw, Egyptian vulture, and African penguin. For some but not all of these species, tourism can extend expected survival time, i.e., benefits outweigh impacts. Precise outcomes depend strongly on population parameters and starting sizes, predation, and ecotourism scale and mechanisms. Tourism does not currently overcome other major conservation threats associated with natural resource extractive industries. Similar calculations for other threatened species are currently limited by lack of basic population data. PMID- 26886877 TI - [Nighttime restlessness in people with dementia in residential care: an explorative field study]. AB - Nighttime restlessness in dementia is an underestimated problem. Although little is known about the prevalence and not every person with dementia struggles with it, nighttime restlessness puts a heavy burden on the persons themselves and their caregivers.This field study explores nighttime restlessness in nursing homes based on two research questions: (1) What is nighttime restlessness according to professional caregivers? and (2) How is nighttime restlessness managed?Data were collected through diaries, interviews with caregivers and one night of observation in eight nursing homes.Wandering and screaming seem to be the most prevalent nighttime agitated behaviours. Caregivers identify many possible causes, but spatial and sensory factors, such as light or noise, were rarely mentioned spontaneously. The observations highlighted that a lot of light and noise is prominent and this might be causing nighttime restlessness.Caregivers try several strategies: for example talking with the resident, put on a light and apply medication or physical restraints.The management of nighttime restlessness requires a holistic approach. Caregivers' attention for and efforts to ameliorate the spatial and sensory environment in the management of nighttime restlessness are limited. PMID- 26886878 TI - Cardiovascular disease as a complication of community-acquired pneumonia. AB - PURPOSE OF REVIEW: Here, we review the incidence, prognosis, potential mechanisms and therapeutic implications of cardiovascular disease in community-acquired pneumonia (CAP). RECENT FINDINGS: Recent evidence suggests that a large proportion of deaths from CAP are attributable to cardiovascular disease, including sudden cardiac death, acute myocardial infarction (MI), arrhythmias and cardiac failure. Up to one-third of patients with CAP may experience cardiovascular complications within 30 days of hospital admission, while data also suggest that CAP managed in the community is associated with increased risk of acute MI. The risk is maximal within a few days of hospitalization with CAP and reduces over time. Most studies suggest that risk is still increased at 1 year, and some suggest risk continues to be increased at 10 years post-CAP. This clearly contributes to the well-recognized increased long-term mortality associated with CAP. The mechanism is not entirely clear, but recent published data have better defined the impact of the host response, including systemic inflammation and platelet activation. The contribution of Streptococcus pneumoniae has also been recently investigated, with animal studies suggesting a direct effect of S. pneumoniae on the myocardium, forming microlesions that heal with resulting myocardial fibrosis. Several studies suggest a key role for the pore-forming toxin pneumolysin in S. pneumoniae-induced cardiac toxicity. SUMMARY: Several therapies have been shown to improve the outcomes in cardiovascular disease, but whether these would be effective in improving outcomes in CAP is unknown. In this review, we argue that cardioprotective treatments may hold the greatest promise in terms of reducing long-term mortality in patients with CAP. PMID- 26886879 TI - Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids. AB - In both eukaryotes and prokaryotes, fatty acid synthases are responsible for the biosynthesis of fatty acids in an iterative process, extending the fatty acid by two carbon units every cycle. Thus, odd numbered fatty acids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fatty acids as substrates for their fatty acid synthases and their downstream enzymes. We fed various odd and short chain fatty acids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fatty acids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fatty acid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fatty acids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fatty acids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fatty acids was only observed in Synechocystis and C. reinhardtii. We further probed fatty acid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fatty acid desaturases. In particular, supplementation with thia fatty acids can alter fatty acid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fatty acids can reveal major differences between fatty acid metabolism in various organisms. Often unnatural fatty acids have antibacterial or even therapeutic properties. Feeding of short precursors now gives us easy access to these extended molecules. PMID- 26886881 TI - Implications of Market Competition, Technology Adoption, and Cost for Surgical Patients. PMID- 26886880 TI - Genome-Wide De Novo Prediction of Cis-Regulatory Binding Sites in Mycobacterium tuberculosis H37Rv. AB - The transcription regulatory system of Mycobacterium tuberculosis (M. tb) remains incompletely understood. In this study, we have applied the eGLECLUBS algorithm to a group of related prokaryotic genomes for de novo genome-wide prediction of cis-regulatory binding sites (CRBSs) in M. tb H37Rv. The top 250 clusters from our prediction recovered 83.3% (50/60) of all known CRBSs in extracted inter operonic sequences of this strain. We further demonstrated that the integration of our prediction results with the ChIP-Seq datasets is very effective in identifying true binding sites of TFs. Using electrophoretic mobility shift assays and real-time RT-PCR, we experimentally verified our prediction of CRBSs for Rv0081, an important transcription factor thought to be involved in regulation of M. tb under hypoxia. PMID- 26886882 TI - Hormonal-stress interactions in precipitating perimenopausal depressive symptoms. PMID- 26886883 TI - Vitamin D and conjugated equine estrogen: the association with coronary artery atherosclerosis in cynomolgus monkeys. AB - OBJECTIVE: To analyze vitamin D3 plasma concentrations among monkeys randomized to oral conjugated equine estrogen (CEE) versus control and the association with coronary artery atherosclerosis (CAA). METHODS: Surgically postmenopausal monkeys (N = 50) were fed an atherogenic diet containing a woman's equivalent of 1000 IU/day of vitamin D3. The monkeys were randomized at baseline to receive CEE (equivalent of 0.45 mg/d, n = 25) or placebo (n = 25). 25-hydroxyvitamin D3 (25OHD3) was measured at baseline and 20 months later. At 20 months, CAA evidence of coronary artery remodeling, and American Heart Association (AHA) severity scores were assessed. RESULTS: The percent change in 25OHD3 concentrations from baseline to 20 months postrandomization was inversely correlated with plaque area of the right coronary artery (P = 0.048), left circumflex artery (P = 0.039), left anterior descending artery (P = 0.017), and AHA severity score (AHA LADmax) (P = 0.016). Those with increased 25OHD3 concentrations who were taking CEE also had significantly lower AHA scores compared with those who were not taking CEE and did not have an increase in 25OHD3 (P = 0.01). CONCLUSIONS: Monkeys with increases in 25OHD3 concentrations had significantly less severe CAA. Those with increases in 25OHD3 with CEE were associated with significantly decreased AHA lesion scores, decreased plaque, and greater coronary artery remodeling. If these findings are present in women, achieving higher 25OHD3 concentrations (or being a vitamin D supplementation "responder") may be associated with cardioprotection, and further studies to evaluate a synergistic effect with CEE and vitamin D on cardiovascular health are needed. PMID- 26886884 TI - Physical therapy for urinary incontinence in postmenopausal women with osteoporosis or low bone density: a randomized controlled trial. AB - OBJECTIVE: To assess the effectiveness of 12 weekly physical therapy sessions for urinary incontinence (UI) compared with a control intervention, for reducing the number of UI episodes measured with the 7-day bladder diary, at 3 months and 1 year postrandomization. METHODS: A single parallel-group randomized controlled trial was conducted at one outpatient public health center, in postmenopausal women aged 55 years and over with osteoporosis or low bone density and UI. Women were randomized to physical therapy (PT) for UI or osteoporosis education. The primary outcome measure was number of leakage episodes on the 7-day bladder diary, assessed at baseline, after treatment and at 1 year. The secondary outcome measures included the pad test and disease-specific quality of life and self efficacy questionnaires assessed at the same timepoints. RESULTS: Forty-eight women participated (24 per group). Two participants dropped out of each group and one participant was deceased before 3-month follow-up. Intention-to-treat analysis was undertaken. At 3 months and 1 year, there was a statistically significant difference in the number of leakage episodes on the 7-day bladder diary (3 mo: P = 0.04; 1 y: P = 0.01) in favor of the PT group. The effect size was 0.34 at 1 year. There were no harms reported. CONCLUSIONS: After a 12-week course of PT once per week for UI, PT group participants had a 75% reduction in weekly median number of leakage episodes, whereas the control group's condition had no improvement. At 1 year, the PT group participants maintained this improvement, whereas the control group's incontinence worsened. PMID- 26886886 TI - Refinement and expansion of a tool for measuring genitourinary syndrome of menopause. PMID- 26886885 TI - The longitudinal relation of stress during the menopausal transition to fibrinogen concentrations: results from the Study of Women's Health Across the Nation. AB - OBJECTIVE: Life course theory suggests that exposures during critical or sensitive periods have particularly profound effects on health. Most research on this subject has focused on the occurrence of such windows early in life. We investigated whether perimenopause, a period of dramatic neuroendocrine changes at midlife, represents a sensitive period for response to stress by evaluating the relation of perceived stress to fibrinogen, a biomarker for inflammation. METHODS: The study sample was composed of participants in the Study of Women's Health Across the Nation, a longitudinal study on women's health during the menopausal transition (n = 3,287). We fitted linear mixed effects models to estimate the longitudinal relationship between stress and menopausal stage and the association between stress and fibrinogen over the menopausal transition. RESULTS: Women in early and late perimenopause reported perceiving higher levels of stress than premenopausal women (P < 0.05), adjusted for confounding variables. This increased perception of stress during perimenopause, however, was unrelated to changes in fibrinogen. CONCLUSIONS: Although neuroendocrine changes during the menopausal transition may exacerbate the negative health effects of stress, the findings of this study do not suggest such interaction, as measured by changes in fibrinogen. The significant association observed between perceived stress and menopause status, however, may still have important implications, given prior literature linking perceived stress with numerous health outcomes. PMID- 26886887 TI - Detection of Talaromyces marneffei from Fresh Tissue of an Inhalational Murine Pulmonary Model Using Nested PCR. AB - Penicilliosis marneffei, often consecutive to the aspiration of Talaromyces marneffei (Penicillium marneffei), continues to be one of the significant causes of morbidity and mortality in immunocompromised patients in endemic regions such as Southeast Asia. Improving the accuracy of diagnosing this disease would aid in reducing the mortality of associated infections. In this study, we developed a stable and reproducible murine pulmonary model that mimics human penicilliosis marneffei using a nebulizer to deliver Talaromyces marneffei (SUMS0152) conidia to the lungs of BALB/c nude mice housed in exposure chamber. Using this model, we further revealed that nested PCR was sensitive and specific for detecting Talaromyces marneffei in bronchoalveolar lavage fluid and fresh tissues. This inhalation model may provide a more representative analysis tool for studying the development of penicilliosis marneffei, in addition to revealing that nested PCR has a predictive value in reflecting pulmonary infection. PMID- 26886888 TI - Modular Synthetic Inverters from Zinc Finger Proteins and Small RNAs. AB - Synthetic zinc finger proteins (ZFPs) can be created to target promoter DNA sequences, repressing transcription. The binding of small RNA (sRNA) to ZFP mRNA creates an ultrasensitive response to generate higher effective Hill coefficients. Here we combined three "off the shelf" ZFPs and three sRNAs to create new modular inverters in E. coli and quantify their behavior using induction fold. We found a general ordering of the effects of the ZFPs and sRNAs on induction fold that mostly held true when combining these parts. We then attempted to construct a ring oscillator using our new inverters. Our chosen parts performed insufficiently to create oscillations, but we include future directions for improvement upon our work presented here. PMID- 26886889 TI - Bimatoprost Increases Mechanosensitivity of Trigeminal Ganglion Neurons Innervating the Inner Walls of Rat Anterior Chambers via Activation of TRPA1. AB - PURPOSE: Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of bimatoprost on the mechanosensitive TG nerve endings in the inner walls of rat anterior chambers, we investigated its effect on their cell bodies in vitro. METHODS: Rat TG neurons innervating the inner walls of the anterior chambers were labeled by anterior chamber injection of 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4 chlorobenzenesulfonate (FAST DiI). Calcium imaging and whole cell patch clamp were used on neuronal cell bodies to detect the activation effect of TRPA1 channels. Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. RESULTS: Bimatoprost mimicked the effect of TRPA1 agonists, allyl isothiocyanate (AITC), and (R)-(+)-WIN55, 212-2 mesylate salt (WIN) in the TG neurons. Bimatoprost induced Ca(2+) influx in HEK293 cells stably transfected with human TRPA1, but not in untransfected cells as AITC and WIN. Moreover, bimatoprost evoked inward currents via TRPA1 activation in FAST DiI labeled TG neurons as WIN. Bimatoprost also enhanced mechanosensitivity of FAST DiI-labeled TG neurons via TRPA1 activation. CONCLUSIONS: Our results indicate that bimatoprost is a novel agonist of TRPA1, and it can enhance mechanosensitivity of TG nerve endings in the inner walls of anterior eye chambers via TRPA1 activation in rats. PMID- 26886892 TI - Choroidal Folds in Astronauts. PMID- 26886891 TI - Species Cross-Reactivity of Antibodies Used to Treat Ophthalmic Conditions. AB - PURPOSE: The species cross-reactivity of the monoclonal antibodies infliximab, bevacizumab, and an anti-VEGF-B antibody, 2H10, in humans and rodents was determined. METHODS: The binding of infliximab to human, mouse, and rat TNF alpha, of bevacizumab to human, mouse, and rat VEGF-A, and of the 2H10 antibody to human, mouse, and rat VEGF-B was evaluated by ELISA. The sequence of human, mouse, and rat TNF-alpha and VEGF-A at the binding sites for infliximab and bevacizumab were compared. RESULTS: Infliximab bound to human TNF-alpha, but no binding to mouse or rat TNF-alpha was detected between 10 pg/mL and 10 MUg/ml. Sequence comparison of the binding site revealed four changes in mouse and five in rat TNF-alpha compared with human. Bevacizumab bound strongly to human VEGF-A, but showed 5-log weaker binding to both mouse and rat VEGF-A. There was a single amino acid substitution in mouse and rat VEGF-A at the bevacizumab binding site. The 2H10 antibody displayed a similar binding profile to human, mouse, and rat VEGF-B. CONCLUSIONS: The species cross-reactivity of monoclonal antibodies should be determined prior to their use in preclinical animal models. The 2H10 antibody binds to human, mouse, and rat VEGF-B making it suitable for testing in rodent models of human disease. PMID- 26886893 TI - Author Response: Choroidal Folds in Astronauts. PMID- 26886890 TI - MRI of Retinal Free Radical Production With Laminar Resolution In Vivo. AB - PURPOSE: Recent studies have suggested the hypothesis that quench-assisted 1/T1 magnetic resonance imaging (MRI) measures free radical production with laminar resolution in vivo without the need of a contrast agent. Here, we test this hypothesis further by examining the spatial and detection sensitivity of quench assisted 1/T1 MRI to strain, age, or retinal cell layer-specific genetic manipulations. METHODS: We studied: adult wild-type mice; mice at postnatal day 7 (P7); cre dependent retinal pigment epithelium (RPE)-specific MnSOD knockout mice; doxycycline-treated Sod2f(lox/flox) mice lacking the cre transgene; and alpha-transducin knockout (Gnat1(-/-)) mice on a C57Bl/6 background. Transretinal 1/T1 profiles were mapped in vivo in the dark without or with antioxidant treatment, or followed by light exposure. We calibrated profiles spatially using optical coherence tomography. RESULTS: Dark-adapted RPE-specific MnSOD knockout mice had greater than normal 1/T1 in the RPE and outer nuclear layers that was corrected to wild-type levels by antioxidant treatment. Dark and light Gnat1(-/-) mice also had greater than normal outer retinal 1/T1 values. In adult wild-type mice, dark values of 1/T1 in the ellipsoid region and in the outer segment were suppressed by 13 minutes of light. By 29 minutes of light, 1/T1 reduction extended to the outer nuclear layer. Gnat1(-/-) mice demonstrated a faster light evoked suppression of 1/T1 values in the outer retina. In P7 mice, transretinal 1/T1 profiles were the same in dark and light. CONCLUSIONS: Quench-assisted MRI has the laminar resolution and detection sensitivity to evaluate normal and pathologic production of free radicals in vivo. PMID- 26886894 TI - Topical Application of Interleukin-28A Attenuates Allergic Conjunctivitis in an Ovalbumin-Induced Mouse Model. AB - PURPOSE: Allergic conjunctivitis (AC) is an immunoglobulin E (IgE)-mediated and helper T cell 2 (Th2)--cell-mediated disease characterized by conjunctival eosinophilic infiltration. Previous study shows that IL-28A had anti-allergic activity in airway disease. In this study, we examined the effect of IL-28A on a mouse model of ovalbumin (OVA)-induced experimental allergic conjunctivitis (EAC). METHODS: Mouse EAC was induced by topical application of OVA after intraperitoneal (IP) sensitization with OVA in aluminum hydroxide (ALUM). Interleukin-28A was administered 1 hour before OVA challenge. Allergic conjunctivitis symptoms, eosinophil infiltration in the conjunctiva, antigen specific IgE in the serum, and Th2 cytokine production by lymph node cells and splenocytes were subsequently analyzed. RESULTS: Topical application of IL-28A to OVA-induced EAC reduced clinical symptoms, serum OVA-specific IgE, and the infiltration of eosinophils in the conjunctiva. In addition, topical administration of IL-28A suppressed the expression of IL-4, IL-5, and IL-13 (Th2 type cytokine) but promoted the expression of IFN-gamma (Th1-type cytokine) by splenocytes and cervical lymph node cells in EAC mice. Immunofluorescence staining showed decrease expression of IL-4 and IL-5 in IL-28A-treated EAC conjunctiva. CONCLUSIONS: Interleukin-28A shows therapeutic potential for allergic conjunctival inflammation. PMID- 26886895 TI - Contamination of Primary Human Corneal Epithelial Cells With an SV40-Transformed Human Corneal Epithelial Cell Line: A Lesson for Cell Biologists in Good Laboratory Practice. PMID- 26886897 TI - Germline mosaicism in osteopathia striata with cranial sclerosis--recurrence in siblings. AB - We report recurrence of osteopathia striata with cranial sclerosis (OSCS) in two full siblings conceived by unaffected parents. Molecular confirmation of OSCS in both siblings was achieved by identification of a novel heterozygous mutation in the WTX gene. Neither parent had clinical features of OSCS nor was the pathogenic mutation demonstrable in DNA extracted from both peripheral blood leucocytes and buccal cells. This case demonstrates germline mosaicism in OSCS and represents the third report of mosaicism affecting the germline in families with OSCS. Previous reports were of parental gonadosomal mosaicism, with one showing recurrence in multiple children. Our observation adds to a body of evidence that suggests that germline mosaicism in OSCS may occur more frequently than believed previously and may have implications for counselling families with OSCS. PMID- 26886898 TI - Transapical Mitral Valve-in-Valve Implantation Using an Edwards SAPIEN 3 Prosthesis. AB - We report a case of transapical mitral valve-in-valve implantation for a deteriorated bioprosthesis using the SAPIEN 3. Our patient, a 79-year-old man, with a history of mitral valve replacement 10 years before, presented with acute dyspnea due to mitral valve dysfunction. He was successfully treated with transapical implantation and had an uneventful recovery. Our case demonstrates the feasibility of using SAPIEN 3 in treating degenerated bioprosthetic mitral valves. PMID- 26886896 TI - Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms. AB - PURPOSE: To examine associations between corneal mechanical thresholds and metrics of dry eye. METHODS: This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. RESULTS: A total of 129 subjects participated in the study (mean age 64 +/- 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's rho = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = -0.13 to -0.27, P < 0.05 for values between -0.18 and 0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (beta = 0.21, SE = 0.03) and corneal pain threshold (beta = -0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). CONCLUSIONS: Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints. PMID- 26886899 TI - Comparison of stroke volumes assessed by three-dimensional echocardiography and transpulmonary thermodilution in a pediatric animal model. AB - To compare stroke volumes (SV) in small hearts assessed by real-time three dimensional echocardiography (3DE) with SV measured by transpulmonary thermodilution (TPTD) and continuous pulse contour analysis (PC) under various hemodynamic conditions. In thirteen anesthetized piglets (range 3.6-7.1 kg) SV were measured by 3DE, TPTD and PC at baseline and during phenylephrine and esmolol administration. 3DE and TPTD measurements were done successively while SV calculated by PC was documented at the time of 3DE. 3DE and TPTD showed a good correlation (r2 = 0.74) and a bias of -1.3 ml (limits of agreement -4.1 to 1.5 ml). While TPTD measured higher SV than 3DE, both methods tracked SV changes with a concordance rate of 91 %. PC and 3DE showed a lower correlation coefficient of r2 = 0.57 and a bias of -2.1 ml (limits of agreement -5.9 to 1.8 ml). Inter- and intra-observer variability of SV measured by 3DE was good with a mean bias <5 %. SV3DE showed a small variance and tracked acute small changes in SV in acceptable concordance with TPTD. PC measured SV with a higher variance and mean difference compared to 3DE. In an experimental setting 3DE has the possibility to offer non invasive assessments of ventricular volumes volume changes. To determine whether 3DE could be used for SV assessment in a clinical routine our results need confirmation in a clinical setting. PMID- 26886900 TI - Radiation Recall Dermatitis With Concomitant Dabrafenib and Pazopanib Therapy. PMID- 26886901 TI - Endoscopic thyroidectomy along with bilateral central neck dissection (ETBC) increases the risk of transient hypoparathyroidism for patients with thyroid carcinoma. AB - Increasing number of patients with thyroid carcinoma, especially young female patients, prefer to choose endoscopic thyroidectomy with bilateral central neck dissection (ETBC) for perfect cosmetic effects. However, the incidence of hypoparathyroidism after ETBC has not been well studied. Ninety six patients with papillary thyroid carcinoma were enrolled. All patients, including 49 ETBC and 47 open surgery patients, underwent total thyroidectomy with bilateral central neck dissection (CND). Some patients also underwent lateral neck dissection simultaneously. The incidence of hypoparathyroidism and parathyroid hormone (PTH) level were examined. Patients in the open surgery group had more advanced lesions, with larger tumor (p = 0.000), older age (p = 0.000), and more serious local involvement. The dissection extent of the open group was significantly larger than that of the ETBC group (p = 0.006). In contrast, the ETBC group with less dissection extent showed a significantly higher incidence of transient hypoparathyroidism than the open group (59.2 vs. 29.6 %, p = 0.004). The average PTH decline of the ETBC group was significantly higher than that of the open group on postoperative day 1 (POD1) (32.1 vs. 21.6 pg/ml, p = 0.010). Furthermore, the ETBC group had a significantly higher portion of patients with a PTH <10 pg/ml on POD1 (p = 0.001). One patient in the ETBC group developed permanent hypoparathyroidism. Autotransplantation and inadvertent removal rates of parathyroid did not differ between the two groups. Although generally considered a safe method for patients with thyroid carcinoma, ETBC may increase the risk of transient hypoparathyroidism compared with conventional open surgery. PMID- 26886902 TI - Cancerous leptomeningitis and familial congenital hypopituitarism. AB - People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies. PMID- 26886903 TI - [Periprosthetic fractures following total hip and knee arthroplasty: Risk factors, epidemiological aspects, diagnostics and classification systems]. AB - Periprosthetic fractures following hip and knee arthroplasty are potentially severe complications. As a fundament in diagnostic and therapeutic procedures, specific classification systems are necessary to ensure an optimal individualized treatment of these sometimes complicated fractures. This review article summarizes the epidemiological aspects, risk factors and diagnostics of periprosthetic hip and knee fractures. The most frequently used location related fracture classifications systems are explained. In addition, the recently introduced unified classification system (UCS), which is applicable to any location of periprosthetic fractures, is described in detail. Initial studies have shown a reliable applicability of the UCS to periprosthetic hip and knee fractures. PMID- 26886905 TI - Changes in Predominance of Pulsed-Field Gel Electrophoresis Profiles of Bordetella pertussis Isolates, United States, 2000-2012. AB - To clarify the characteristics of circulating Bordetella pertussis isolates, we used pulsed-field gel electrophoresis (PFGE) to analyze 5,262 isolates collected in the United States during 2000-2012. We found 199 PFGE profiles; 5 profiles accounted for 72% of isolates. The most common profile, CDC013, accounted for 35% 46% of isolates tested from 2000-2009; however, the proportion of isolates of this profile rapidly decreased in 2010. Profile CDC237, first seen in 2009, increased rapidly and accounted for 29% of 2012 isolates. No location bias was observed among profiles during 2000-2010, but differences were observed among isolates from different states during 2012. Predominant profiles match those observed in recent European PFGE studies. PFGE profile changes are concurrent with other recent molecular changes in B. pertussis and may be contributing to the reemergence of pertussis in the United States. Continued PFGE monitoring is critical for understanding the changing epidemiology of pertussis. PMID- 26886904 TI - High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity. AB - OBJECTIVES: Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). METHODS: Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. RESULTS: HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. CONCLUSIONS: HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. KEY POINTS: * US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. * HIFU can considerably reduce tumour volume and cancer-related pain. * Patients treated with HIFU experienced significant and lasting reduction of pain intensity. * HIFU has a crucial clinical benefit for patients with pancreatic cancer. PMID- 26886906 TI - Comprehensive Map of Molecules Implicated in Obesity. AB - Obesity is a global epidemic affecting over 1.5 billion people and is one of the risk factors for several diseases such as type 2 diabetes mellitus and hypertension. We have constructed a comprehensive map of the molecules reported to be implicated in obesity. A deep curation strategy was complemented by a novel semi-automated text mining system in order to screen 1,000 full-length research articles and over 90,000 abstracts that are relevant to obesity. We obtain a scale free network of 804 nodes and 971 edges, composed of 510 proteins, 115 genes, 62 complexes, 23 RNA molecules, 83 simple molecules, 3 phenotype and 3 drugs in "bow-tie" architecture. We classify this network into 5 modules and identify new links between the recently discovered fat mass and obesity associated FTO gene with well studied examples such as insulin and leptin. We further built an automated docking pipeline to dock orlistat as well as other drugs against the 24,000 proteins in the human structural proteome to explain the therapeutics and side effects at a network level. Based upon our experiments, we propose that therapeutic effect comes through the binding of one drug with several molecules in target network, and the binding propensity is both statistically significant and different in comparison with any other part of human structural proteome. PMID- 26886907 TI - Addition of Phenylboronic Acid to Malus domestica Pollen Tubes Alters Calcium Dynamics, Disrupts Actin Filaments and Affects Cell Wall Architecture. AB - A key role of boron in plants is to cross-link the cell wall pectic polysaccharide rhamnogalacturonan-II (RG-II) through borate diester linkages. Phenylboronic acid (PBA) can form the same reversible ester bonds but cannot cross-link two molecules, so can be used as an antagonist to study the function of boron. This study aimed to evaluate the effect of PBA on apple (Malus domestica) pollen tube growth and the underlying regulatory mechanism. We observed that PBA caused an inhibition of pollen germination, tube growth and led to pollen tube morphological abnormalities. Fluorescent labeling, coupled with a scanning ion-selective electrode technique, revealed that PBA induced an increase in extracellular Ca2+ influx, thereby elevating the cytosolic Ca2+ concentration [Ca2+]c and disrupting the [Ca2+]c gradient, which is critical for pollen tube growth. Moreover the organization of actin filaments was severely perturbed by the PBA treatment. Immunolocalization studies and fluorescent labeling, together with Fourier-transform infrared analysis (FTIR) suggested that PBA caused an increase in the abundance of callose, de-esterified pectins and arabinogalactan proteins (AGPs) at the tip. However, it had no effect on the deposition of the wall polymers cellulose. These effects are similar to those of boron deficiency in roots and other organs, indicating that PBA can induce boron deficiency symptoms. The results provide new insights into the roles of boron in pollen tube development, which likely include regulating [Ca2+]c and the formation of the actin cytoskeleton, in addition to the synthesis and assembly of cell wall components. PMID- 26886908 TI - A Finite Element Model Approach to Determine the Influence of Electrode Design and Muscle Architecture on Myoelectric Signal Properties. AB - INTRODUCTION: Surface electromyography (sEMG) is the measurement of the electrical activity of the skeletal muscle tissue detected at the skin's surface. Typically, a bipolar electrode configuration is used. Most muscles have pennate and/or curved fibres, meaning it is not always feasible to align the bipolar electrodes along the fibres direction. Hence, there is a need to explore how different electrode designs can affect sEMG measurements. METHOD: A three layer finite element (skin, fat, muscle) muscle model was used to explore different electrode designs. The implemented model used as source signal an experimentally recorded intramuscular EMG taken from the biceps brachii muscle of one healthy male. A wavelet based intensity analysis of the simulated sEMG signal was performed to analyze the power of the signal in the time and frequency domain. RESULTS: The model showed muscle tissue causing a bandwidth reduction (to 20-92- Hz). The inter-electrode distance (IED) and the electrode orientation relative to the fibres affected the total power but not the frequency filtering response. The effect of significant misalignment between the electrodes and the fibres (60 degrees -90 degrees ) could be reduced by increasing the IED (25-30 mm), which attenuates signal cancellation. When modelling pennated fibres, the muscle tissue started to act as a low pass filter. The effect of different IED seems to be enhanced in the pennated model, while the filtering response is changed considerably only when the electrodes are close to the signal termination within the model. For pennation angle greater than 20 degrees , more than 50% of the source signal was attenuated, which can be compensated by increasing the IED to 25 mm. CONCLUSION: Differences in tissue filtering properties, shown in our model, indicates that different electrode designs should be considered for muscle with different geometric properties (i.e. pennated muscles). PMID- 26886909 TI - MRI of the normal appendix in children: data toward a new reference standard. AB - BACKGROUND: Magnetic resonance imaging (MRI) might prove useful in the diagnostic evaluation of pediatric appendicitis in the effort to avoid exposing children to the ionizing radiation of CT, yet there is a paucity of literature describing the normal range of appearances of the pediatric appendix on MRI. OBJECTIVE: To investigate MRI characteristics of the normal appendix to aid in establishing a reference standard in the pediatric population. MATERIALS AND METHODS: We conducted a retrospective study of children and young adults (<=18 years of age) who underwent lumbar spine or pelvis MRI between Jan. 1, 2013, and Dec. 31, 2013, for indications unrelated to appendicitis. Two board-certified radiologists independently reviewed all patients' MRI examinations for appendix visualization, diameter, intraluminal content signal, and presence of periappendiceal inflammation or free fluid. We used the Cohen kappa statistic and Spearman correlation coefficient to assess reader agreement on qualitative and quantitative data, respectively. RESULTS: Three hundred forty-six patients met inclusion criteria. Both readers visualized the appendix in 192/346 (55.5%) patients (kappa = 0.88, P < 0.0001). Estimated median appendix diameter was 5 mm for reader 1 and 6 mm for reader 2 ([25th, 75th] quartiles = [5, 6] mm; range, 2 11 mm; r = 0.81, P < 0.0001). Appendix intraluminal signal characteristics were variable. Periappendiceal inflammation was present in 0/192 (0%) and free fluid in 6/192 (3.1%) MRI examinations (kappa = 1.0). CONCLUSION: The normal appendix was seen on MRI in approximately half of pediatric patients, with a mean diameter of ~5-6 mm, variable intraluminal signal characteristics, no adjacent inflammatory changes, and rare surrounding free fluid. PMID- 26886910 TI - Child abuse: we have problems. PMID- 26886911 TI - The etiology and significance of fractures in infants and young children: a critical multidisciplinary review. AB - This paper addresses significant misconceptions regarding the etiology of fractures in infants and young children in cases of suspected child abuse. This consensus statement, supported by the Child Abuse Committee and endorsed by the Board of Directors of the Society for Pediatric Radiology, synthesizes the relevant scientific data distinguishing clinical, radiologic and laboratory findings of metabolic disease from findings in abusive injury. This paper discusses medically established epidemiology and etiologies of childhood fractures in infants and young children. The authors also review the body of evidence on the role of vitamin D in bone health and the relationship between vitamin D and fractures. Finally, the authors discuss how courts should properly assess, use, and limit medical evidence and medical opinion testimony in criminal and civil child abuse cases to accomplish optimal care and protection of the children in these cases. PMID- 26886912 TI - Free-breathing motion-corrected late-gadolinium-enhancement imaging improves image quality in children. AB - BACKGROUND: The value of late-gadolinium-enhancement (LGE) imaging in the diagnosis and management of pediatric and congenital heart disease is clear; however current acquisition techniques are susceptible to error and artifacts when performed in children because of children's higher heart rates, higher prevalence of sinus arrhythmia, and inability to breath-hold. Commonly used techniques in pediatric LGE imaging include breath-held segmented FLASH (segFLASH) and steady-state free precession-based (segSSFP) imaging. More recently, single-shot SSFP techniques with respiratory motion-corrected averaging have emerged. OBJECTIVE: This study tested and compared single-shot free breathing LGE techniques with standard segmented breath-held techniques in children undergoing LGE imaging. MATERIALS AND METHODS: Thirty-two consecutive children underwent clinically indicated late-enhancement imaging using intravenous gadobutrol 0.15 mmol/kg. Breath-held segSSFP, breath-held segFLASH, and free-breathing single-shot SSFP LGE sequences were performed in consecutive series in each child. Two blinded reviewers evaluated the quality of the images and rated them on a scale of 1-5 (1 = poor, 5 = superior) based on blood pool myocardial definition, presence of cardiac motion, presence of respiratory motion artifacts, and image acquisition artifact. We used analysis of variance (ANOVA) to compare groups. RESULTS: Patients ranged in age from 9 months to 18 years, with a mean +/- standard deviation (SD) of 13.3 +/- 4.8 years. R-R interval at the time of acquisition ranged 366-1,265 milliseconds (ms) (47-164 beats per minute [bpm]), mean +/- SD of 843+/-231 ms (72+/-21 bpm). Mean +/- SD quality ratings for long-axis imaging for segFLASH, segSSFP and single-shot SSFP were 3.1+/-0.9, 3.4+/-0.9 and 4.0+/-0.9, respectively (P < 0.01 by ANOVA). Mean +/- SD quality ratings for short-axis imaging for segFLASH, segSSFP and single-shot SSFP were 3.4+/-1, 3.8+/-0.9 and 4.3+/-0.7, respectively (P < 0.01 by ANOVA). CONCLUSION: Single-shot late-enhancement imaging with motion-corrected averaging is feasible in children, robust at high heart rates and with variable R-R intervals, and can be performed without breath-holding with higher image quality ratings than standard breath-held techniques. Use of free-breathing single-shot motion-corrected technique does not compromise LGE image quality in children who can hold their breath, and it can significantly improve image quality in children who cannot hold their breath or who have significant arrhythmia. PMID- 26886914 TI - Langerhans cell histiocytosis of the digestive tract identified on an upper gastrointestinal examination. AB - Langerhans cell histiocytosis (LCH) with involvement of the gastrointestinal tract is rare and typically identified in patients with systemic disease. We describe a 16-month-old girl who initially presented with bilious vomiting, failure to thrive and a rash. An upper gastrointestinal (GI) examination revealed loss of normal mucosal fold pattern and luminal narrowing within the duodenum, prompting endoscopic biopsy. Langerhans cell histiocytosis of the digestive tract was confirmed by histopathology. A skeletal survey and skin biopsy identified other systemic lesions. Although uncommon, it is important to consider LCH in the differential diagnosis for gastrointestinal symptoms of unclear origin, especially when seen with concurrent rash. Findings of gastrointestinal involvement on upper GI examination include loss of normal mucosal fold pattern and luminal narrowing in the few published case reports. PMID- 26886913 TI - Early imaging findings in germ cell tumors arising from the basal ganglia. AB - BACKGROUND: It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. OBJECTIVE: To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. MATERIALS AND METHODS: We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (>=3 cm) with cyst. We also assessed temporal changes of the MR images. RESULTS: On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. CONCLUSION: Early stage basal ganglia germ cell tumors appear as ill defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. PMID- 26886915 TI - A review of the literature for intra-arterial chemotherapy used to treat retinoblastoma. AB - Retinoblastoma is a malignancy of the retina that usually presents before the age of 5 years. Sporadic retinoblastoma is most often unilateral and with no hereditary influence, whereas familial retinoblastoma presents unilaterally or bilaterally in conjunction with genetic inheritance. Several treatments have been attempted with the goals of saving the child's life, salvaging the eye, and preserving vision. Alternative methods including external beam radiation, systemic chemotherapy and focal therapies have been shown to be effective but carry a risk of enucleation and other complications proportional to the severity of the tumor. Selective intra-arterial chemotherapy for retinoblastoma began in 1988 in Japan and has emerged in the last 7 years in the United States as a feasible, effective and minimally invasive treatment option. We review the retinoblastoma treatment literature focusing on intra-arterial chemotherapy. PMID- 26886916 TI - Safety and effectiveness of percutaneous cholecystostomy in critically ill children who are immune compromised. AB - BACKGROUND: Acalculous cholecystitis is known to develop in critically ill patients without cystic duct obstruction. In the past, treatment for acalculous cholecystitis has been cholecystectomy; however, many children who are critically ill are Percutaneous cholecystostomy is likely the procedure of choice in this subgroup of patients. OBJECTIVE: To assess the safety and effectiveness of percutaneous cholecystostomy in critically ill and immune-compromised children with acalculous cholecystitis. MATERIALS AND METHODS: Retrospective review of immune-compromised and critically ill children who underwent percutaneous cholecystostomy between 2006 and 2013. Diagnostic imaging performed included ultrasound, CT and hepatobiliary scintigraphy. Every percutaneous cholecystostomy was performed using imaging guidance. RESULTS: Ten critically ill and immune compromised children with acalculous cholecystitis underwent percutaneous cholecystostomy. Seven boys and 3 girls, ranging in age from 10 months to 15 years 8 months, were treated. Six of the immune-compromised children had received a bone marrow transplant for leukemia (5 children) or severe combined immunodeficiency (SCID) (1 child), and ranged from 18 to 307 days post bone marrow transplant at the time of their percutaneous cholecystostomy. Of the remaining four immune-compromised children with acalculous cholecystitis who underwent percutaneous cholecystostomy, two had leukemia, one had SCID and lymphoma, and the fourth was undergoing treatment for undifferentiated germ cell tumor. The 10 percutaneous gallbladder drains were placed using a transhepatic approach, except one unintentional transperitoneal approach. There were no complications. Three gallbladder drains were removed in Interventional Radiology. Those three patients had a return to normal gallbladder function and didn't require cholecystectomy. Two drains were removed during cholecystectomy and another as an outpatient. Four patients died in the hospital due to multiorgan system failure, with indwelling gallbladder drains. CONCLUSION: Percutaneous cholecystostomy is a safe procedure in immune-compromised and critically ill children with acalculous cholecystitis. Percutaneous cholecystostomy may obviate the need for future cholecystectomy. PMID- 26886918 TI - Multivessel versus Single Vessel Angioplasty in Non-ST Elevation Acute Coronary Syndromes: A Systematic Review and Metaanalysis. AB - BACKGROUND: Multivessel disease is common in acute coronary syndrome patients. However, if multivessel percutaneous coronary intervention is superior to culprit vessel angioplasty has not been systematically addressed. METHODS: A metaanalysis was conducted including studies that compared multivessel angioplasty with culprit-vessel angioplasty among non-ST elevation ACS patients. Since all studies were observational adjusted estimates of effects were used. Pooled estimates of effects were computed using the generic inverse of variance with a random effects model. RESULTS: Twelve studies were included (n = 117,685). Median age was 64.1 years, most patients were male, 29.3% were diabetic and 36,9% had previous myocardial infarction. Median follow-up was 12 months. There were no significant differences in mortality risk (HR 0.79; 95% CI 0.58 to 1.09; I2 67.9%), with moderate inconsistency. Also, there were no significant differences in the risk of death or MI (HR 0.90; 95% CI 0.69 to 1.17; I2 62.3%), revascularization (HR 0.76; 95% CI 0.55 to 1.05; I2 49.9%) or in the combined incidence of death, myocardial infarction or revascularization (HR 0.83; 95% CI 0.66 to 1.03; I2 70.8%). All analyses exhibited a moderate degree of inconsistency. Subgroup analyses by design reduced the inconsistency of the analyses on death or myocardial infarction, revascularization and death, myocardial infarction or revascularization. There was evidence of publication bias (Egger's test p = 0.097). CONCLUSION: Routine multivessel angioplasty in non-ST elevation acute coronary syndrome patients with multivessel disease was not superior to culprit vessel angioplasty. Randomized controlled trials comparing safety and effectiveness of both strategies in this setting are needed. PMID- 26886919 TI - Radiative Peristaltic Flow of Jeffrey Nanofluid with Slip Conditions and Joule Heating. AB - Mixed convection peristaltic flow of Jeffrey nanofluid in a channel with compliant walls is addressed here. The present investigation includes the viscous dissipation, thermal radiation and Joule heating. Whole analysis is performed for velocity, thermal and concentration slip conditions. Related problems through long wavelength and low Reynolds number are examined for stream function, temperature and concentration. Impacts of thermal radiation, Hartman number, Brownian motion parameter, thermophoresis, Joule heating and slip parameters are explored in detail. Clearly temperature is a decreasing function of Hartman number and radiation parameter. PMID- 26886917 TI - Whole-Body Vibration Partially Reverses Aging-Induced Increases in Visceral Adiposity and Hepatic Lipid Storage in Mice. AB - At old age, humans generally have declining muscle mass and increased fat deposition, which can increase the risk of developing cardiometabolic diseases. While regular physical activity postpones these age-related derangements, this is not always possible in the elderly because of disabilities or risk of injury. Whole-body vibration (WBV) training may be considered as an alternative to physical activity particularly in the frail population. To explore this possibility, we characterized whole-body and organ-specific metabolic processes in 6-month and 25-month old mice, over a period of 14 weeks of WBV versus sham training. WBV training tended to increase blood glucose turnover rates and stimulated hepatic glycogen utilization during fasting irrespective of age. WBV was effective in reducing white fat mass and hepatic triglyceride content only in old but not in young mice and these reductions were related to upregulation of hepatic mitochondrial uncoupling of metabolism (assessed by high-resolution respirometry) and increased expression of uncoupling protein 2. Because these changes occurred independent of changes in food intake and whole-body metabolic rate (assessed by indirect calorimetry), the liver-specific effects of WBV may be a primary mechanism to improve metabolic health during aging, rather than that it is a consequence of alterations in energy balance. PMID- 26886920 TI - The role of titin and extracellular matrix remodelling in heart failure with preserved ejection fraction. AB - Heart failure with preserved ejection fraction (HFpEF) is characterised by a high incidence of metabolic comorbidities that share the potential to induce both systemic and coronary microvascular inflammation and oxidative stress. These pathophysiological alterations contribute to increased passive stiffness of the myocardium and to diastolic dysfunction, both hallmarks of HFpEF. Passive myocardial stiffness depends mainly on two components: the extracellular matrix (ECM) and the cardiomyocytes. Quantitative and qualitative changes in collagen metabolism leading to myocardial fibrosis determine the ECM-based stiffness of the myocardium. Different noninvasive diagnostic tools to assess myocardial fibrosis are being developed, some of which have demonstrated to correlate with clinical status and prognosis. Cardiomyocytes mainly alter the passive stiffness through alterations in the giant myofilament titin, which serves as a spring. By modifying its phosphorylation state or by direct oxidative effects, titin determines cardiomyocyte-based passive stiffness. Probably the relative importance of cardiomyocyte-based changes is more important in the beginning of the disease, whereas ECM-based changes become more prominent in the more advanced stages. The present review focuses on these changes in ECM and cardiomyocytes in HFpEF and their potential prognostic and therapeutic implications. PMID- 26886921 TI - Erratum to: Echocardiography and cardiac resynchronization therapy, friends or foes? PMID- 26886922 TI - Atelectasis After Endoscopic Resection: Relations and Prediction. PMID- 26886924 TI - A fluorescence anisotropy-based assay for determining the activity of tissue transglutaminase. AB - Tissue transglutaminase (TGase 2) is the most abundantly expressed enzyme of the transglutaminase family and involved in a large variety of pathological processes, such as neurodegenerative diseases, disorders related to autoimmunity and inflammation as well as tumor growth, progression and metastasis. As a result, TGase 2 represents an attractive target for drug discovery and development, which requires assays that allow for the characterization of modulating agents and are appropriate for high-throughput screening. Herein, we report a fluorescence anisotropy-based approach for the determination of TGase 2's transamidase activity, following the time-dependent increase in fluorescence anisotropy due to the enzyme-catalyzed incorporation of fluorescein- and rhodamine B-conjugated cadaverines 1-3 (acyl acceptor substrates) into N,N dimethylated casein (acyl donor substrate). These cadaverine derivatives 1-3 were obtained by solid-phase synthesis. To allow efficient conjugation of the rhodamine B moiety, different linkers providing secondary amine functions, such as sarcosyl and isonipecotyl, were introduced between the cadaverine and xanthenyl entities in compounds 2 and 3, respectively, with acyl acceptor 3 showing the most optimal substrate properties of the compounds investigated. The assay was validated for the search of both irreversible and reversible TGase 2 inhibitors using the inactivators iodoacetamide and a recently published L-lysine derived acrylamide and the allosteric binder GTP, respectively. In addition, the fluorescence anisotropy-based method was proven to be suitable for high throughput screening (Z' factor of 0.86) and represents a non-radioactive and highly sensitive assay for determining the active TGase 2 concentration. PMID- 26886925 TI - The debate continues: is urine culture indicated in neonates with prolonged jaundice? PMID- 26886923 TI - Comparative Analysis of Protocols to Induce Human CD4+Foxp3+ Regulatory T Cells by Combinations of IL-2, TGF-beta, Retinoic Acid, Rapamycin and Butyrate. AB - Regulatory T cells (Tregs) suppress other immune cells and are critical mediators of peripheral tolerance. Therapeutic manipulation of Tregs is subject to numerous clinical investigations including trials for adoptive Treg transfer. Since the number of naturally occurring Tregs (nTregs) is minute, it is highly desirable to develop a complementary approach of inducing Tregs (iTregs) from naive T cells. Mouse studies exemplify the importance of peripherally induced Tregs as well as the applicability of iTreg transfer in different disease models. Yet, procedures to generate iTregs are currently controversial, particularly for human cells. Here we therefore comprehensively compare different established and define novel protocols of human iTreg generation using TGF-beta in combination with other compounds. We found that human iTregs expressed several Treg signature molecules, such as Foxp3, CTLA-4 and EOS, while exhibiting low expression of the cytokines Interferon-gamma, IL-10 and IL-17. Importantly, we identified a novel combination of TGF-beta, retinoic acid and rapamycin as a robust protocol to induce human iTregs with superior suppressive activity in vitro compared to currently established induction protocols. However, iTregs generated by these protocols did not stably retain Foxp3 expression and did not suppress in vivo in a humanized graft-versus-host-disease mouse model, highlighting the need for further research to attain stable, suppressive iTregs. These results advance our understanding of the conditions enabling human iTreg generation and may have important implications for the development of adoptive transfer strategies targeting autoimmune and inflammatory diseases. PMID- 26886927 TI - Changes in quality of life after a diagnosis of cancer: a 2-year study comparing breast cancer and melanoma patients. AB - PURPOSE: Longitudinal studies addressing change in health-related quality of life (HRQoL) following a diagnosis of cancer have mainly focused on a single cancer type, and little is known about the differences in HRQoL over time according to the type of tumor. The current study aims to compare the change in HRQoL over 2 years following breast cancer or melanoma diagnosis and socio-demographic variables associated with HRQoL over time. METHODS: Patients recently diagnosed with breast cancer (n = 215) or melanoma (n = 78) completed surveys within 1 month of diagnosis and 6, 12, and 24 months later. Multilevel modeling analyses were used to compare the evolution over time of HRQoL dimensions, as measured by the EORTC QLQ-C30, in both cancers. Longitudinal effect of socio-demographic variables on HRQoL was also assessed. RESULTS: Consistent with the literature, both cancer patients experienced decreased HRQoL scores following the diagnosis before improving over time. However, our analyses revealed that this rebound effect may occur at diverse times over the course of the illness according to the type of cancer. In addition, HRQoL over time was positively associated with age and negatively related to living with a partner regardless of the type of cancer. CONCLUSIONS: The results of the present study suggest that support in hospital units should be specific and depend on the cancer type. PMID- 26886926 TI - Health-related quality of life among veterans in addictions treatment: identifying behavioral targets for future intervention. AB - BACKGROUND: US veterans report lower health-related quality of life (HRQoL) relative to the general population. Identifying behavioral factors related to HRQoL that are malleable to change may inform interventions to improve well-being in this vulnerable group. PURPOSE: The current study sought to characterize HRQoL in a largely male sample of veterans in addictions treatment, both in relation to US norms and in association with five recommended health behavior practices: regularly exercising, managing stress, having good sleep hygiene, consuming fruits and vegetables, and being tobacco free. METHODS: We assessed HRQoL with 250 veterans in addictions treatment (96 % male, mean age 53, range 24-77) using scales from four validated measures. Data reduction methods identified two principal components reflecting physical and mental HRQoL. Model testing of HRQoL associations with health behaviors adjusted for relevant demographic and treatment-related covariates. RESULTS: Compared to US norms, the sample had lower HRQoL scores. Better psychological HRQoL was associated with higher subjective social standing, absence of pain or trauma, lower alcohol severity, and monotonically with the sum of health behaviors (all p < 0.05). Specifically, psychological HRQoL was associated with regular exercise, stress management, and sleep hygiene. Regular exercise also related to better physical HRQoL. The models explained >40 % of the variance in HRQoL. CONCLUSIONS: Exercise, sleep hygiene, and stress management are strongly associated with HRQoL among veterans in addictions treatment. Future research is needed to test the effect of interventions for improving well-being in this high-risk group. PMID- 26886928 TI - Erratum to: Uptake of a fluorescent L-glucose derivative 2-NBDLG into three dimensionally accumulating insulinoma cells in a phloretin-sensitive manner. PMID- 26886931 TI - Erratum to: Biography of Aniceto Baltasar, MD. PMID- 26886929 TI - Bariatric Surgery in Obese Patients with Type 1 Diabetes: Effects on Weight Loss and Metabolic Control. AB - BACKGROUND: Type 1 diabetes patients, although typically lean, experience an increased prevalence of obesity, and bariatric surgery is considered in severe cases. Bariatric surgery in such patients leads to significant weight loss and decreased insulin requirements; however, effects on glycemic control remain discussed. We assessed, in obese patients with type 1 diabetes, the effects of bariatric surgery upon body weight, body composition, and glycemic control, including the occurrence of hypoglycemic events. METHODS: Thirteen obese patients with type 1 diabetes who underwent bariatric surgery (Roux-en-Y gastric bypass n = 6, sleeve gastrectomy n = 7) were matched with obese patients without diabetes and with type 2 diabetes patients during 12 months of follow-up. Outcomes included body weight, DXA-assessed body composition, HbA1c, and incidence of hypoglycemia. RESULTS: At 12 months, median surgery-induced weight loss was 27.9 % (21.1-33.3), 26.1 % (24.8-29.7), and 27.5 % (21.8-32.1) in patients with type 1 diabetes, type 2 diabetes, and without diabetes, respectively, with no significant differences across the groups. Similar findings were observed for body fat changes. At 12 months, median HbA1c decreased from 8.3 to 7.6 % in type 1 diabetes patients versus 8.0 to 5.9 % in type 2 diabetes patients (P = 0.04 between the groups). In type 1 diabetes patients, the number of reported minor hypoglycemia increased transiently only at 6 months. Two patients reported severe hypoglycemia (one episode each). CONCLUSIONS: Type 1 diabetes patients benefit from bariatric surgery in terms of weight loss and glycemic control. Close monitoring of insulin therapy appears warranted to prevent minor hypoglycemia in the first months post-surgery. PMID- 26886930 TI - Stigma and Knowledge as Determinants of Recommendation and Referral Behavior of General Practitioners and Internists. AB - BACKGROUND: Despite reported effectiveness, weight loss surgery (WLS) still remains one of the least preferred options for outpatient providers, especially in Germany. The aim of this study was to examine the effect of stigma and knowledge on recommendation of WLS and referral to a surgeon by general practitioners (GPs) and internists. METHOD: The sample consists of 201 GPs and internists from Germany. The questionnaire included questions on the perceived effectiveness of WLS, the frequency of recommendations of WLS, and the frequency of referral to WLS. Stigma, as well as knowledge was also assessed in this context. Linear and logistic regression models were conducted. A mediation analysis was carried out within post hoc analysis. RESULTS: Knowledge (b = 0.258, p < 0.001) and stigma towards surgery (b = -0.129, p = 0.013) were related to the frequency of recommendation of WLS. Additionally, respondents, who were more likely to express negative attitudes towards WLS, were less likely to recommend WLS and thus refer patients to WLS (b = -0.107, p < 0.05). Furthermore, respondents with more expertise on WLS were more likely to recommend and thus refer patients to WLS (b = 0.026, p < 0.05). CONCLUSION: This study showed that stigma plays a role when it comes to defining treatment pathways for patients with obesity. The question remains how this might influence the patients and their decision regarding their treatment selection. Interventions are required to make treatment decisions by physicians or patients independent of social pressure due to stigma. PMID- 26886932 TI - Can Novel Management Practice Improve Soil and Environmental Quality and Sustain Crop Yield Simultaneously? AB - Little is known about management practices that can simultaneously improve soil and environmental quality and sustain crop yields. The effects of novel and traditional management practices that included a combination of tillage, crop rotation, and N fertilization on soil C and N, global warming potential (GWP), greenhouse gas intensity (GHGI), and malt barley (Hordeum vulgarie L.) yield and quality were examined under non-irrigated and irrigated cropping systems from 2008 to 2011 in eastern Montana and western North Dakota, USA. In loamy soil under non-irrigated condition in eastern Montana, novel and traditional management practices were no-till malt barley-pea (Pisum sativum L.) with 80 kg N ha(-1) and conventional till malt barley-fallow with 80 kg N ha(-1), respectively. In sandy loam soil under irrigated and non-irrigated conditions in western North Dakota, novel and traditional management practices included no-till malt barley-pea with 67 (non-irrigated) to 134 kg N ha(-1) (irrigated) and conventional till malt barley with 67 (non-irrigated) to 134 kg N ha(-1) (irrigated), respectively. Compared with the traditional management practice, soil organic C (SOC) and total N (STN) at 0-120 cm were 5% greater with the novel management practice under non-irrigated condition in eastern Montana and under irrigated condition in western North Dakota, but were not different under non irrigated condition in western North Dakota. In both places under irrigated and non-irrigated conditions, total applied N rate, residual soil NO3-N content at 0 120 cm, global warming potential (GWP), and greenhouse gas intensity (GHGI) were 15 to 70% lower with the novel than the traditional management practice. Malt barley yield and quality were not different between the two practices in both places. Novel management practices, such as no-till malt barley-pea with reduced N rate, can simultaneously enhance soil and environmental quality, reduce N input, and sustain crop yield compared with traditional practices in the northern Great Plains, USA. PMID- 26886934 TI - Super-slim endoscopy, in a patient with a Crohn's ileocecal valve stricture, for assessment of mucosal healing. PMID- 26886933 TI - Bread Wheat (Triticum aestivum L.) Grain Protein Concentration Is Related to Early Post-Flowering Nitrate Uptake under Putative Control of Plant Satiety Level. AB - The strong negative correlation between grain protein concentration (GPC) and grain yield (GY) in bread wheat complicates the simultaneous improvement of these traits. However, earlier studies have concluded that the deviation from this relationship (grain protein deviation or GPD) has strong genetic basis. Genotypes with positive GPD have an increased ability to uptake nitrogen (N) during the post-flowering period independently of the amount of N taken up before flowering, suggesting that genetic variability for N satiety could enable the breakage of the negative relationship. This study is based on two genotypes markedly contrasted for GPD grown under semi-hydroponic conditions differentiated for nitrate availability both before and after flowering. This allows exploration of the genetic determinants of post-flowering N uptake (PANU) by combining whole plant sampling and targeted gene expression approaches. The results highlights the correlation (r2 = 0.81) with GPC of PANU occurring early during grain development (flowering-flowering + 250 degree-days) independently of GY. Early PANU was in turn correlated (r2 = 0.80) to the stem-biomass increment after flowering through its effect on N sink activity. Differences in early PANU between genotypes, despite comparable N statuses at flowering, suggest that genetic differences in N satiety could be involved in the establishment of the GPC. Through its strong negative correlation with genes implied in N assimilation, root nitrate concentration appears to be a good marker for evaluating instantaneous plant N demand, and may provide valuable information on the genotypic N satiety level. This trait may help breeders to identify genotypes having high GPC independently of their GY. PMID- 26886935 TI - The use of a T drain tube to treat anastomotic leaks. PMID- 26886937 TI - Introduction to the Second Section of the Special Issue: Invited Papers from the 2015 APAHC Conference. PMID- 26886936 TI - Clinical recurrence and re-resection rates after extensive vs. segmental colectomy in Crohn's colitis: a retrospective cohort study. AB - BACKGROUND: The aim of the present study was to document long-term clinical recurrence and re-resection rates of segmental and extended colectomy in patients with Crohn's colitis and to identify risk factors causing recurrence. METHODS: Records of patients with isolated colonic Crohn's disease who underwent colectomy between 1995 and 2013 and were followed at our medical center were identified. Data on age at diagnosis, gender, smoking, disease location at diagnosis, perianal and rectal disease, indication for surgery, preoperative disease duration, type of operation, primary anastomosis at first operation, length of resected specimen, recurrence of symptoms, postoperative medication, reoperation, and total follow-up time were retrieved. RESULTS: Thirty-five suitable patients (18 segmental colectomy, 17 extensive colectomy; 17 males; mean age at operation 36.6 years) were identified. Mean age at primary operation was 36 years. The mean preoperative disease duration was 121 months. Postoperative medical treatment was needed in 10 (56 %) patients undergoing segmental colectomy and in 16 (94 %) of those undergoing extensive colectomy (p = 0.01). There was longer reoperation free survival in the segmental colectomy patient group (p = 0.02) and also a trend toward longer symptom-free survival compared to the extensive colectomy patient group (p = 0.105). There was no correlation between the length of resected bowel and recurrence. Patients operated on at a younger age did not have a higher rate of recurrence of symptoms. Shorter disease duration, smoking, and male gender were risk factors for clinical recurrence. CONCLUSIONS: Segmental resection with primary anastomosis can be safely performed in patients with limited Crohn's colitis with reasonable clinical recurrence rates. PMID- 26886938 TI - Rectal HSV-2 Infection May Increase Rectal SIV Acquisition Even in the Context of SIVDeltanef Vaccination. AB - Prevalent HSV-2 infection increases the risk of HIV acquisition both in men and women even in asymptomatic subjects. Understanding the impact of HSV-2 on the mucosal microenvironment may help to identify determinants of susceptibility to HIV. Vaginal HSV-2 infection increases the frequency of cells highly susceptible to HIV in the vaginal tissue of women and macaques and this correlates with increased susceptibility to vaginal SHIV infection in macaques. However, the effect of rectal HSV-2 infection on HIV acquisition remains understudied. We developed a model of rectal HSV-2 infection in macaques in combination with rectal SIVmac239Deltanef (SIVDeltanef) vaccination and our results suggest that rectal HSV-2 infection may increase the susceptibility of macaques to rectal SIVmac239 wild-type (wt) infection even in SIVDeltanef-infected animals. Rectal SIVDeltanef infection/vaccination protected 7 out of 7 SIVDeltanef-infected macaques from SIVmac239wt rectal infection (vs 12 out of 16 SIVDeltanef-negative macaques), while 1 out of 3 animals co-infected with SIVDeltanef and HSV-2 acquired SIVmac239wt infection. HSV-2/SIVmac239wt co-infected animals had increased concentrations of inflammatory factors in their plasma and rectal fluids and a tendency toward higher acute SIVmac239wt plasma viral load. However, they had higher blood CD4 counts and reduced depletion of CCR5+ CD4+ T cells compared to SIVmac239wt-only infected animals. Thus, rectal HSV-2 infection generates a pro-inflammatory environment that may increase susceptibility to rectal SIV infection and may impact immunological and virological parameters during acute SIV infection. Studies with larger number of animals are needed to confirm these findings. PMID- 26886939 TI - Aberrant expression and hormonal regulation of Galectin-3 in endometriosis women with infertility. AB - OBJECTIVE: To investigate the role and potential molecular mechanism of Galectin 3 (Gal-3) in the etiology of endometriosis-associated infertility. METHODS: We detected Gal-3 expression in eutopic endometrium from women with endometriosis associated infertility and healthy women without endometriosis or infertility. We then evaluated Gal-3 expression in endometrial glandular epithelial cells (EECs) and endometrial stromal cells (ESCs) and investigated its response to hormone stimulation in EECs and ESCs from both groups of women. RESULTS: Results of real time PCR and western blot analysis showed Gal-3 expression in both proliferative and secretory stages of the menstrual cycle decreased significantly in women with endometriosis-associated infertility compared to healthy women. The changes in expression of Gal-3 were more dramatic in EECs than ESCs. Moreover, estrogen (E2) and progesterone (P4) induced Gal-3 expression in EECs of healthy groups, and P4 was more significant than E2 and combined E2 and P4 (E2P4). However, in the endometriosis group, P4 failed to induce a similar increase in Gal-3 expression. CONCLUSIONS: Our results suggest that aberrant expression of Gal-3 might contribute to infertility in patients with endometriosis due to progesterone resistance. PMID- 26886940 TI - Prospective, systematically recorded mycophenolate safety data in Graves' orbitopathy. AB - CONTEXT: The antiproliferative mechanism of mycophenolate acid (MPA) suggests a beneficial effect in patients with Graves' orbitopathy (GO). OBJECTIVE: To systematically analyze for the first time adverse events (AEs) during MPA treatment in GO. DESIGN: Prospective longitudinal study. SETTING: Academic tertiary referral center with a joint thyroid-eye clinic. PATIENTS: Fifty-three consecutive, unselected patients with clinically active and moderate-to-severe GO. METHODS: MPA 0.720 g was given once daily for 24-weeks in GO patients. AEs were documented and coded according to the standardized medical dictionary for regulatory activities (MedDRA). AE were followed up and seriousness as defined by ICH-guideline E6 was documented. All AEs were analyzed regarding a possible underlying cause and if not, graded as side effect (SE). RESULTS: Fifty GO patients (93 %) had Graves' disease, 37 (70 %) and 29 (54.7 %) were female and smoker, respectively. Thirty-six patients (68 %) reported at least one AE. A total of 88 AEs were documented, most frequent AEs were insomnia (N = 6), fatigue (N = 5) and optic neuropathy (N = 5), while other AEs occurred in up to three patients (5.6 %), only. In 12 (23 %) patients, at least one SE occurred. All 17 reported SE, i.e. mild infections and gastrointestinal intolerance were within the known safety profile of MPA. No patient dropped MPA medication because of drug-induced SE. Most AEs showed a recovered (76 %) or recovering (16 %) outcome. Seven (13 %) patients were hospitalized, five (62 %) due to optic neuropathy, none of these events was graded as SE. CONCLUSIONS: MedDRA-coded data documented the good tolerance of a moderate MPA dose in GO patients. PMID- 26886943 TI - Meta-analysis of the association between a serotonin transporter 5-HTTLPR polymorphism and smoking cessation. AB - 5-HTTLPR is one of the candidate genes influencing addiction. Recent studies have reported that the 5-HTTLPR genotype is associated with smoking behaviour, but its influence is still controversial. Thus, we reviewed the smoking-cessation outcomes among previously reported studies by comparing the 5-HTTLPR polymorphism. In total, eight studies including 3206 participants for the present meta-analysis were assessed and the S/S, S/L and L/L genotypes were compared with respect to smoking-cessation outcomes. The results of comparing 5-HTTLPR genotypes were as follows: odds ratio (OR)=1.044 and 95% confidence interval (CI)=0.751-1.078 for S/S versus S/L; OR=0.862 and 95% CI=0.690-1.077 for S/L versus L/L; and OR=0.924 and 95% CI=0.689-1.433 for S/S versus L/L. We found no significant association between 5-HTTLPR and smoking cessation, but 5-HTTLPR remains an important smoking-related candidate gene. PMID- 26886944 TI - Tumor Growth Kinetics Before and After First-line Chemotherapy in Metastatic Castration-resistant Prostate Cancer: A Prostate-specific Antigen-based Retrospective Analysis. AB - OBJECTIVES: The role of the tumor growth fraction has been investigated poorly in metastatic castration-resistant prostate cancer (mCRPC). The aim of this study was to assess whether some prostate-specific antigen (PSA)-related variables of tumor cell kinetics predict the overall survival in early and late mCRPC, and to explore changes in the tumor growth fraction after chemotherapy. METHODS: A retrospective analysis of 3 tumor cell kinetic variables in patients with mCRPC receiving first-line chemotherapy has been performed. The PSA-related tumor growth rate, the log ratio, and the tumor response have been measured at 3 different times. A further analysis has been performed after stratification by the Gleason score and chemotherapy. Finally, tumor growth after progression to chemotherapy has been explored. RESULTS: G at castration resistance is significantly associated with survival after chemotherapy among patients with a low Gleason score (r=-0.650, P-value=0.022). At the time of first-line chemotherapy, both G and PSA response rates report a significant relationship with survival. At the time of postchemotherapy progression, only the G after 12 weeks of chemotherapy maintains a relationship with survival in patients with a low Gleason score (r=-0.483, P-value=0.023); in particular, a tumor growth rate < 0.5%/day appears to be associated with a poor postprogression survival. Despite the lack of correlation between postprogression G and postprogression survival, the response to chemotherapy defines 2 groups with different growth characteristics. CONCLUSIONS: Among patients with mCRPC, tumor cell kinetics appears to be able to predict the outcome, especially in tumors with a low Gleason score. PMID- 26886941 TI - A large insertion in intron 2 of the TYRP1 gene associated with American Palomino phenotype in American mink. AB - A number of American mink phenotypes display a range of brownish colours. One of these phenotypes, namely American Palomino (b (P) b (P) ) (AP) has been found to be associated with the tyrosinase-related protein 1 (TYRP1) gene by genotyping microsatellite markers in one sire family. Trials for amplifying the genomic DNA and cDNA at the beginning of intron 2 of AP TYRP1 revealed the presence of a large insertion of approximately eight kb. The insertion most likely disrupts different elements necessary for the splicing of intron 2 of the TYRP1 gene. In AP RNAseq data indicate, however, the presence of the wild-type (wt) transcript at very low levels and Western blot reveals three products when using an antibody raised against middle part of the TYRP1 protein. One individual from another brown mink phenotype-commercially named Dawn-was also investigated at the molecular level by long-range PCR and the same size insertion appears to be present. By this we suggest that certain modifiers of TYRP1 would induce different brown colour degradation, which results in at least two different phases of brown. PMID- 26886945 TI - Stage I and II Endometrial Adenocarcinoma: Analysis of 2009 FIGO Staging Revision and Impact on Survival by Adjuvant Therapy. AB - BACKGROUND: In 2009, the International Federation of Gynecology and Obstetrics revised the staging classification for endometrial cancer. Mucosal cervical involvement was eliminated from the criteria and only those with stromal cervical involvement were considered stage II. We examined the implications of the staging changes and the survival impact of adjuvant therapy in stage I to II endometrial adenocarcinoma. MATERIALS AND METHODS: Data were obtained from the National Oncology Data Alliance. Stage I to II endometrial adenocarcinoma patients diagnosed between 1988 and 2008 were identified and grouped according to the 1988 International Federation of Gynecology and Obstetrics staging. Multivariate analysis (MVA) was performed using proportional hazards model; comparison of Kaplan-Meier survival curves was based on the log-rank statistic. RESULTS: A total of 14,158 patients with stage I to II endometrial adenocarcinoma were identified with a median follow-up of 41 months. Adjuvant external-beam radiation therapy (EBRT) and adjuvant vaginal brachytherapy (VB) were positive predictors for overall survival (OS) only in IC, IIA, and IIB. On MVA, stages IA and IB OS did not differ (P=0.17), IIA had worse OS compared with IC (P<0.05), and IIA OS did not differ from IIB (P=0.57). Neither IA nor IB benefited from adjuvant radiotherapy on MVA. However, both IC and IIA had OS improvements with VB+/-EBRT (P<0.05) with the greatest impact from the VB. CONCLUSIONS: Mucosal cervical involvement represents a risk factor and should be considered when determining adjuvant therapy. Adjuvant therapy provided no survival benefit in 1988 stage IA or IB; however, adjuvant radiotherapy is recommended in the management of IC, IIA, and IIB. PMID- 26886946 TI - Phase I Trial of Dose-escalated Whole Liver Irradiation With Hepatic Arterial Fluorodeoxyuridine/Leucovorin and Streptozotocin Followed by Fluorodeoxyuridine/Leucovorin and Chemoembolization for Patients With Neuroendocrine Hepatic Metastases. AB - OBJECTIVES: We have previously shown that refractory neuroendocrine tumors can respond to moderate doses of chemoradiotherapy. We completed a dose-escalation phase I/II trial combining hepatic arterial (HA) chemotherapy, chemoembolization, and dose-escalated whole liver radiotherapy to determine the maximum safe dose of radiation that could be delivered and to make a preliminary assessment of response. MATERIALS AND METHODS: From 2002 to 2009, 19 patients with symptomatic neuroendocrine liver metastases who failed somatostatin analog therapy were enrolled. HA fluorodeoxyuridine, leucovorin, and streptozotocin were delivered, as concurrent whole liver radiotherapy was dose escalated from 24 to 32 Gy in 2 Gy fractions, with a target rate of dose-limiting grade >=3 radiation-induced liver disease of 10%. Eight weeks later, for patients without grade >=3 liver or grade >=4 any toxicity, a 72-hour infusion of HA fluorodeoxyuridine and leucovorin was given, followed by transarterial chemoembolization. RESULTS: Eleven patients completed the entire protocol and received 24 to 32 Gy. No patients developed radiation-induced liver disease; 7 had grade 3 to 4 transiently increased liver function tests, and 4 had other grade 4 toxicities. Three patients (14%) had partial response, 16 (84%) stable disease. Median freedom from local progression and overall survival were 35.3 and 54.6 months, respectively. CONCLUSIONS: Thirty-two in 2 Gy daily fractions can be delivered safely when combined with HA chemotherapy and subsequent transarterial chemoembolization. However, although objective responses were observed, this combination was not significantly better than our prior approaches. Further treatment intensification strategies, including individualized dose escalation for radiation-tolerant livers, and improved radiosensitization should be investigated, along with improved systemic therapy. PMID- 26886947 TI - Medicare Cancer Screening in the Context of Clinical Guidelines: 2000 to 2012. AB - OBJECTIVES: Cancer screening is a ubiquitous and controversial public health issue, particularly in the elderly population. Despite extensive evidence-based guidelines for screening, it is unclear how cancer screening has changed in the Medicare population over time. We characterize trends in cancer screening for the most common cancer types in the Medicare fee-for-service (FFS) program in the context of conflicting guidelines from 2000 to 2012. MATERIALS AND METHODS: We performed a descriptive analysis of retrospective claims data from the Medicare FFS program based on billing codes. Our data include all claims for Medicare part B beneficiaries who received breast, colorectal (CRC), or prostate cancer screening from 2000 to 2012 based on billing codes. We utilize a Monte Carlo permutation method to detect changes in screening trends. RESULTS: In total, 231,416,732 screening tests were analyzed from 2000 to 2012, representing an average of 436.8 tests per 1000 beneficiaries per year. Mammography rates declined 7.4%, with digital mammography extensively replacing film. CRC cancer screening rates declined overall. As a percentage of all CRC screening tests, colonoscopy grew from 32% to 71%. Prostate screening rates increased 16% from 2000 to 2007, and then declined to 7% less than its 2000 rate by 2012. DISCUSSION: Both the aggressiveness of screening guidelines and screening rates for the Medicare FFS population peaked and then declined from 2000 to 2012. However, guideline publications did not consistently precede utilization trend shifts. Technology adoption, practical and financial concerns, and patient preferences may have also contributed to the observed trends. Further research should be performed on the impact of multiple, conflicting guidelines in cancer screening. PMID- 26886948 TI - A Meta-Analysis of the Association Between Radiation Therapy and Survival for Surgically Resected Soft-Tissue Sarcoma. AB - OBJECTIVES: Radiotherapy for soft-tissue sarcoma (STS) has been shown to reduce local recurrence, but without clear improvement in survival. We conducted a meta analysis to study the association between radiotherapy and survival in patients undergoing surgery for STS. METHODS: A systematic review was conducted from PubMed, EMBASE, Web of Science, and Cochrane databases. Our population of interest consisted of adults with primary extremity, chest wall, trunk, or back STS. Our metameters were either an odds or hazard ratio for mortality. A bias score was generated for each study based on margin status and grade. RESULTS: Of 1044 studies, 30 met inclusion criteria for final analysis. The pooled odds ratio in patients receiving radiation was 0.94 (95% confidence interval [CI], 0.78 1.14). The pooled estimate of the hazards ratio in patients receiving radiation was 0.87 (95% CI, 0.73-1.03) overall and 0.65 (95% CI, 0.52-0.82) for studies judged to be at low risk of bias. Significant publication bias was not seen. CONCLUSIONS: High-quality studies reporting adjusted hazard ratios are associated with improved survival in patients receiving radiotherapy for STS. Studies in which odds ratios are calculated from event data and those that do not report adjusted outcomes do not show the same association, likely due to confounding by indication. PMID- 26886949 TI - Pre-ESRD Care and Mortality in Incident ESRD Patients With Multiple Myeloma. AB - OBJECTIVES: The relationship between mortality and pre-ESRD (end-stage renal disease) nephrology care in incident ESRD patients with multiple myeloma (MM) as the primary cause of renal failure has not been examined. MATERIALS AND METHODS: Among 439,206 incident US hemodialysis patients with MM as the primary cause of ESRD (June 1, 2005 to May 31, 2009) identified using the US Renal Data System, adjusted odds ratios (OR) for reported pre-ESRD nephrology care for ESRD due to MM (n=4561) versus other causes (n=434,645) were calculated. The association of pre-ESRD nephrology care with subsequent mortality in MM-ESRD patients was examined. RESULTS: MM-ESRD patients were less likely to have any predialysis nephrology care in the year before initiation of dialysis (34.8% vs. 58.5%; OR=0.38; 95% confidence interval [CI], 0.34-0.43) compared with patients with ESRD due to other causes. MM-ESRD patients compared with others were more likely to have catheters on first dialysis (91.8% vs. 75.6%; OR=4.15; 95% CI, 3.54 4.86). Incident MM-ESRD patients receiving predialysis care for >=6 months had significantly lower 1-year mortality (hazard ratio 0.89; 95% CI, 0.82-0.97 and 0.88; 95% CI, 0.80-0.96, respectively), relative to those without this care. A catheter for dialysis access was associated with a 1.6-fold increase in 1-year mortality in incident MM-ESRD (hazard ratio 1.55; 95% CI, 1.32-1.83). CONCLUSIONS: MM-ESRD patients were less likely to have predialysis nephrology care and more likely to use catheters on first dialysis. However, predialysis care is independently associated with lower mortality in MM-ESRD patients. Predialysis care should be prioritized in MM patients approaching ESRD. PMID- 26886950 TI - Stabilization of Cu7 clusters in azide networks: syntheses, structures and magnetic behaviour. AB - Two new azide bridged copper(II) coordination polymer compounds, [Cu7(N3)14(C3H10N2)(C4H13N3)]n (I) and [Cu7(N3)14(C3H10N2)(C5H15N3)2]n (II) [where C3H10N2 = 1,2-diaminopropane (1,2-DAP); C4H13N3 = diethylenetriamine (DETA); C5H15N3 = N-2-aminoethyl-1,3-propanediamine (AEDAP)] were prepared by employing a room temperature diffusion technique involving three layers. Single crystal studies reveal that both compounds I and II, have similar connectivity forming Cu7 clusters through end-on (EO) bonding of the azide. The Cu7 clusters are connected through end-to-end (EE) connectivity of the azides forming three dimensional structures. Magnetic studies confirmed the ferromagnetic interactions within the Cu7 units and revealed the occurrence of concomitant ferro- and antiferro-magnetic interactions between these clusters. As a result I behaves as a weak-ferromagnet with TC = 10 K. PMID- 26886951 TI - Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer. AB - Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body's response to TH, and individualized therapy may be necessary in such patients. PMID- 26886952 TI - The Role of Prophylactic Central Neck Dissection in the Treatment of Differentiated Thyroid Cancer. AB - The utility and efficacy of prophylactic central neck dissection with total thyroidectomy for the treatment of differentiated thyroid cancer has been debated in the literature over the past few decades. Proponents of prophylactic central neck dissection support its routine use with the notion that it reduces local recurrence, increases accuracy in TNM staging, and reduces surgical morbidity associated with reoperation. Conversely, those against the use of routine prophylactic central neck dissection argue there is no clear evidence which shows a reduction in recurrence or added benefit to survival, while the procedure increases the risk for complications and morbidity. This article discusses the role of prophylactic central neck dissection in the setting of thyroid cancer and reviews recently published literature to evaluate efficacy and safety of this procedure. PMID- 26886953 TI - The Mystery of Michelangelo Buonarroti's Goiter. AB - Whilst painting the vault of the Sistine Chapel, Michelangelo Buonarroti left an autographical sketch that revealed a prominence at the front of his hyper extended neck. This image was recently diagnosed as goiter. The poet Michelangelo in a sonnet dated 1509 described himself as being afflicted by goiter similarly to the cats in the northern Italian Lombardy, a region with endemic goiter. Several narratives extended this sonnet into a pathological theory. The analyses of Michelangelo's works, however, his portraits and self-portraits, of poems and major biographies, have not indicated the likelihood of goiter. This investigation makes an attempt to assess the diagnosis on clinical as well as iconographical grounds. PMID- 26886955 TI - A Risk-adapted Approach to Follow-up in Differentiated Thyroid Cancer. AB - The last 10 years have seen a renewed interest in a risk-adapted approach to the management of differentiated thyroid cancer. This review outlines a state-of-the art approach to individualized management in which the original follow-up plan that was developed based on initial risk stratification is modified over time as new data become available. This risk-adapted follow-up approach allows clinicians to determine the intensity of follow-up and management recommendations in response to real-time dynamic risk assessments which may change over time. PMID- 26886954 TI - Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma. AB - Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC. PMID- 26886956 TI - External Beam Radiation in Differentiated Thyroid Carcinoma. AB - The treatment of differentiated thyroid carcinoma (DTC) is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI). External beam radiotherapy (EBRT) is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient's age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT. PMID- 26886957 TI - Genetic Testing in Differentiated Thyroid Carcinoma: Indications and Clinical Implications. AB - Differentiated thyroid cancer (DTC) is a common and diverse endocrine malignancy. In most patients DTC results in an indolent and curable disease. Nevertheless, disease recurrence rates are relatively high (10%-30%), while 5% of the patients are resistant to conventional treatment and some of these patients are incurable. Over the past 20 years much progress has been made in identifying genetic changes that occur in DTC. In addition, studies aimed to understand the role of these genetic changes in tumorigenesis and their effects on the clinical characteristics of the disease have been conducted. The accrued knowledge has set the stage for development of genetic tests aimed to identify these changes in samples obtained from DTC patients and use this information in the clinical decision process. This paper reviews genetic changes that were identified in DTC, and how the emerging data obtained by genetic testing are currently used to gain key information on the diagnosis, risk stratification, and personalized care of DTC patients. PMID- 26886958 TI - Trends of Thyroid Cancer in Israel: 1980-2012. AB - OBJECTIVES: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980-2012, in light of the global trends. METHODS: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. RESULTS: In 1980-2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98-6.93, driven almost entirely by papillary carcinoma (APCs 5.75 8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980-2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC -1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to >=90% in both population groups and both genders. CONCLUSIONS: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID- 26886959 TI - Risk Stratification in Differentiated Thyroid Cancer: An Ongoing Process. AB - Thyroid cancer is an increasingly common malignancy, with a rapidly rising prevalence worldwide. The social and economic ramifications of the increase in thyroid cancer are multiple. Though mortality from thyroid cancer is low, and most patients will do well, the risk of recurrence is not insignificant, up to 30%. Therefore, it is important to accurately identify those patients who are more or less likely to be burdened by their disease over years and tailor their treatment plan accordingly. The goal of risk stratification is to do just that. The risk stratification process generally starts postoperatively with histopathologic staging, based on the AJCC/UICC staging system as well as others designed to predict mortality. These do not, however, accurately assess the risk of recurrence/persistence. Patients initially considered to be at high risk may ultimately do very well yet be burdened by frequent unnecessary monitoring. Conversely, patients initially thought to be low risk, may not respond to their initial treatment as expected and, if left unmonitored, may have higher morbidity. The concept of risk-adaptive management has been adopted, with an understanding that risk stratification for differentiated thyroid cancer is dynamic and ongoing. A multitude of variables not included in AJCC/UICC staging are used initially to classify patients as low, intermediate, or high risk for recurrence. Over the course of time, a response-to-therapy variable is incorporated, and patients essentially undergo continuous risk stratification. Additional tools such as biochemical markers, genetic mutations, and molecular markers have been added to this complex risk stratification process such that this is essentially a continuum of risk. In recent years, additional considerations have been discussed with a suggestion of pre-operative risk stratification based on certain clinical and/or biologic characteristics. With the increasing prevalence of thyroid cancer but stable mortality, this risk stratification may identify those in whom the risk of conventional surgical treatment may outweigh the benefit. This review aims to outline the process of risk stratification and highlight the important concepts that are involved and those that are continuously evolving. PMID- 26886961 TI - A Two-Dimensional Lock-In Algorithm for Signal Analysis in Patterned Images. AB - GOAL: We extend a classic signal processing algorithm, the lock-in amplifier, to two dimensions to extract the signal in patterned images. METHODS: The algorithm was evaluated using simulated image data and experimental microscopy images to determine the fluorescence signal of fluorescently labeled proteins adsorbed on surfaces patterned with chemical vapor deposition. RESULTS: The algorithm was capable of retrieving the signal with a signal-to-noise ratio as low as -20 dB. Optimal parameters were determined for the pattern design. CONCLUSION: The lock in algorithm is a powerful technique for 1/f noise removal. SIGNIFICANCE: The methodology holds promise not only for the measurement of adsorption events on patterned surfaces but in all situations where a signal has to be extracted from a noisy background in two or more dimensions. PMID- 26886960 TI - What is the Minimal Surgery for Papillary Thyroid Carcinoma? AB - Although thyroid surgery for treatment of papillary thyroid carcinoma (PTC) has been practiced for more than 100 years, there is still controversy regarding the minimal surgery needed for cure. The main reason for this controversy is lack of prospective randomized trials. The data accumulated in the last four decades indicate that hemithyroidectomy can be sufficient and safely practiced in low risk patients with PTC. Patients <45 years of age with a single tumor less than 2 cm, with no lymphatic spread, and in the absence of other risk factors, can be equally managed by hemithyroidectomy or total thyroidectomy. A slight increase in the risk of vocal cord paralysis and hypocalcemia after total thyroidectomy suggests that hemithyroidectomy is appropriate for the management of patients with stage T1 disease. Any choice regarding the extent of surgery should be made with the patient and his family and in a multidisciplinary setup, which has been shown to improve decision-making procedures before the operation and during follow-up. PMID- 26886962 TI - In-Vivo Automatic Nuclear Cataract Detection and Classification in an Animal Model by Ultrasounds. AB - OBJECTIVE: To early detect nuclear cataract in vivo and automatically classify its severity degree, based on the ultrasound technique, using machine learning. METHODS: A 20-MHz ophthalmic ultrasound probe with a focal length of 8.9 mm and an active diameter of 3 mm was used. Twenty-seven features in time and frequency domain were extracted for cataract detection and classification with support vector machine (SVM), Bayes, multilayer perceptron, and random forest classifiers. Fifty rats were used: 14 as control and 36 as study group. An animal model for nuclear cataract was developed. Twelve rats with incipient, 13 with moderate, and 11 with severe cataract were obtained. The hardness of the nucleus and the cortex regions was objectively measured in 12 rats using the NanoTest. RESULTS: Velocity, attenuation, and frequency downshift significantly increased with cataract formation ( ). The SVM classifier showed the higher performance for the automatic classification of cataract severity, with a precision, sensitivity, and specificity of 99.7% (relative absolute error of 0.4%). A statistically significant difference was found for the hardness of the different cataract degrees ( P = 0.016). The nucleus showed a higher hardness increase with cataract formation ( P = 0.049 ). A moderate-to-good correlation between the features and the nucleus hardness was found in 23 out of the 27 features. CONCLUSION: The developed methodology made possible detecting the nuclear cataract in-vivo in early stages, classifying automatically its severity degree and estimating its hardness. SIGNIFICANCE: Based on this work, a medical prototype will be developed for early cataract detection, classification, and hardness estimation. PMID- 26886963 TI - Scattering and Diffraction of Elastodynamic Waves in a Concentric Cylindrical Phantom for MR Elastography. AB - AIM: The focus of this paper is to report on the design and construction of a multiply connected phantom for use in magnetic resonance elastography (MRE)-an imaging technique that allows for the noninvasive visualization of the displacement field throughout an object from externally driven harmonic motion-as well as its inverse modeling with a closed-form analytic solution which is derived herein from first principles. METHODS: Mathematically, the phantom is described as two infinite concentric circular cylinders with unequal complex shear moduli, harmonically vibrated at the exterior surface in a direction along their common axis. Each concentric cylinder is made of a hydrocolloid with its own specific solute concentration. They are assembled in a multistep process for which custom scaffolding was designed and built. A customized spin-echo-based MR elastography sequence with a sinusoidal motion-sensitizing gradient was used for data acquisition on a 9.4 T Agilent small-animal MR scanner. Complex moduli obtained from the inverse model are used to solve the forward problem with a finite-element method. RESULTS: Both complex shear moduli show a significant frequency dependence (p 0.001) in keeping with previous work. CONCLUSION: The novel multiply connected phantom and mathematical model are validated as a viable tool for MRE studies. SIGNIFICANCE: On a small enough scale much of physiology can be mathematically modeled with basic geometric shapes, e.g., a cylinder representing a blood vessel. This study demonstrates the possibility of elegant mathematical analysis of phantoms specifically designed and carefully constructed for biomedical MRE studies. PMID- 26886964 TI - Dosimetric Characteristics of an EMF Delivery System Based on a Real-Time Impedance Measurement Device. AB - In this paper, the dosimetric characterization of an EMF exposure setup compatible with real-time impedance measurements of adherent biological cells is proposed. The EMF are directly delivered to the 16-well format plate used by the commercial xCELLigence apparatus. Experiments and numerical simulations were carried out for the dosimetric analysis. The reflection coefficient was less than -10 dB up to 180 MHz and this exposure system can be matched at higher frequencies up to 900 and 1800 MHz. The specific absorption rate (SAR) distribution within the wells containing the biological medium was calculated by numerical finite-difference time domain simulations and results were verified by temperature measurements at 13.56 MHz. Numerical SAR values were obtained at the microelectrode level where the biological cells were exposed to EMF including 13.56, 900, and 1800 MHz. At 13.56 MHz, the SAR values, within the cell layer and the 270-MUL volume of medium, are 1.9e3 and 3.5 W/kg/incident mW, respectively. PMID- 26886965 TI - Discriminative Bayesian Dictionary Learning for Classification. AB - We propose a Bayesian approach to learn discriminative dictionaries for sparse representation of data. The proposed approach infers probability distributions over the atoms of a discriminative dictionary using a finite approximation of Beta Process. It also computes sets of Bernoulli distributions that associate class labels to the learned dictionary atoms. This association signifies the selection probabilities of the dictionary atoms in the expansion of class specific data. Furthermore, the non-parametric character of the proposed approach allows it to infer the correct size of the dictionary. We exploit the aforementioned Bernoulli distributions in separately learning a linear classifier. The classifier uses the same hierarchical Bayesian model as the dictionary, which we present along the analytical inference solution for Gibbs sampling. For classification, a test instance is first sparsely encoded over the learned dictionary and the codes are fed to the classifier. We performed experiments for face and action recognition; and object and scene-category classification using five public datasets and compared the results with state-of the-art discriminative sparse representation approaches. Experiments show that the proposed Bayesian approach consistently outperforms the existing approaches. PMID- 26886966 TI - Higher-Order Graph Principles towards Non-Rigid Surface Registration. AB - This paper casts surface registration as the problem of finding a set of discrete correspondences through the minimization of an energy function, which is composed of geometric and appearance matching costs, as well as higher-order deformation priors. Two higher-order graph-based formulations are proposed under different deformation assumptions. The first formulation encodes isometric deformations using conformal geometry in a higher-order graph matching problem, which is solved through dual-decomposition and is able to handle partial matching. Despite the isometry assumption, this approach is able to robustly match sparse feature point sets on surfaces undergoing highly anisometric deformations. Nevertheless, its performance degrades significantly when addressing anisometric registration for a set of densely sampled points. This issue is rigorously addressed subsequently through a novel deformation model that is able to handle arbitrary diffeomorphisms between two surfaces. Such a deformation model is introduced into a higher-order Markov Random Field for dense surface registration, and is inferred using a new parallel and memory efficient algorithm. To deal with the prohibitive search space, we also design an efficient way to select a number of matching candidates for each point of the source surface based on the matching results of a sparse set of points. A series of experiments demonstrate the accuracy and the efficiency of the proposed framework, notably in challenging cases of large and/or anisometric deformations, or surfaces that are partially occluded. PMID- 26886967 TI - Spatially Variant Resolution Modelling for Iterative List-Mode PET Reconstruction. AB - A spatially variant resolution modelling technique is presented which estimates the system matrix on-the-fly during iterative list-mode reconstruction. This is achieved by redistributing the endpoints of each list-mode event according to derived probability density functions describing the detector response function and photon acollinearity, at each iteration during the reconstruction. Positron range is modelled using an image-based convolution. When applying this technique it is shown that the maximum-likelihood expectation maximisation (MLEM) algorithm is not compatible with an obvious acceleration strategy. The image space reconstruction algorithm (ISRA), however, after being adapted to a list-mode based implementation, is well-suited to the implementation of the model. A comparison of ISRA and MLEM is made to confirm that ISRA is a suitable alternative to MLEM. We demonstrate that this model agrees with measured point spread functions and we present results showing an improvement in resolution recovery, particularly for off-centre objects, as compared to commercially available software, as well as the standard technique of using a stationary Gaussian convolution to model the resolution, for equal iterations and only slightly higher computation time. PMID- 26886968 TI - Combining Generative and Discriminative Representation Learning for Lung CT Analysis With Convolutional Restricted Boltzmann Machines. AB - The choice of features greatly influences the performance of a tissue classification system. Despite this, many systems are built with standard, predefined filter banks that are not optimized for that particular application. Representation learning methods such as restricted Boltzmann machines may outperform these standard filter banks because they learn a feature description directly from the training data. Like many other representation learning methods, restricted Boltzmann machines are unsupervised and are trained with a generative learning objective; this allows them to learn representations from unlabeled data, but does not necessarily produce features that are optimal for classification. In this paper we propose the convolutional classification restricted Boltzmann machine, which combines a generative and a discriminative learning objective. This allows it to learn filters that are good both for describing the training data and for classification. We present experiments with feature learning for lung texture classification and airway detection in CT images. In both applications, a combination of learning objectives outperformed purely discriminative or generative learning, increasing, for instance, the lung tissue classification accuracy by 1 to 8 percentage points. This shows that discriminative learning can help an otherwise unsupervised feature learner to learn filters that are optimized for classification. PMID- 26886969 TI - Fast Convolutional Neural Network Training Using Selective Data Sampling: Application to Hemorrhage Detection in Color Fundus Images. AB - Convolutional neural networks (CNNs) are deep learning network architectures that have pushed forward the state-of-the-art in a range of computer vision applications and are increasingly popular in medical image analysis. However, training of CNNs is time-consuming and challenging. In medical image analysis tasks, the majority of training examples are easy to classify and therefore contribute little to the CNN learning process. In this paper, we propose a method to improve and speed-up the CNN training for medical image analysis tasks by dynamically selecting misclassified negative samples during training. Training samples are heuristically sampled based on classification by the current status of the CNN. Weights are assigned to the training samples and informative samples are more likely to be included in the next CNN training iteration. We evaluated and compared our proposed method by training a CNN with (SeS) and without (NSeS) the selective sampling method. We focus on the detection of hemorrhages in color fundus images. A decreased training time from 170 epochs to 60 epochs with an increased performance-on par with two human experts-was achieved with areas under the receiver operating characteristics curve of 0.894 and 0.972 on two data sets. The SeS CNN statistically outperformed the NSeS CNN on an independent test set. PMID- 26886970 TI - Association Between Changes in Mammographic Image Features and Risk for Near-Term Breast Cancer Development. AB - The purpose of this study is to develop and test a new computerized model for predicting near-term breast cancer risk based on quantitative assessment of bilateral mammographic image feature variations in a series of negative full field digital mammography (FFDM) images. The retrospective dataset included series of four sequential FFDM examinations of 335 women. The last examination in each series ("current") and the three most recent "prior" examinations were obtained. All "prior" examinations were interpreted as negative during the original clinical image reading, while in the "current" examinations 159 cancers were detected and pathologically verified and 176 cases remained cancer-free. From each image, we initially computed 158 mammographic density, structural similarity, and texture based image features. The absolute subtraction value between the left and right breasts was selected to represent each feature. We then built three support vector machine (SVM) based risk models, which were trained and tested using a leave-one-case-out based cross-validation method. The actual features used in each SVM model were selected using a nested stepwise regression analysis method. The computed areas under receiver operating characteristic curves monotonically increased from 0.666+/-0.029 to 0.730+/-0.027 as the time-lag between the "prior" (3 to 1) and "current" examinations decreases. The maximum adjusted odds ratios were 5.63, 7.43, and 11.1 for the three "prior" (3 to 1) sets of examinations, respectively. This study demonstrated a positive association between the risk scores generated by a bilateral mammographic feature difference based risk model and an increasing trend of the near-term risk for having mammography-detected breast cancer. PMID- 26886971 TI - Automatic Hookworm Detection in Wireless Capsule Endoscopy Images. AB - Wireless capsule endoscopy (WCE) has become a widely used diagnostic technique to examine inflammatory bowel diseases and disorders. As one of the most common human helminths, hookworm is a kind of small tubular structure with grayish white or pinkish semi-transparent body, which is with a number of 600 million people infection around the world. Automatic hookworm detection is a challenging task due to poor quality of images, presence of extraneous matters, complex structure of gastrointestinal, and diverse appearances in terms of color and texture. This is the first few works to comprehensively explore the automatic hookworm detection for WCE images. To capture the properties of hookworms, the multi scale dual matched filter is first applied to detect the location of tubular structure. Piecewise parallel region detection method is then proposed to identify the potential regions having hookworm bodies. To discriminate the unique visual features for different components of gastrointestinal, the histogram of average intensity is proposed to represent their properties. In order to deal with the problem of imbalance data, Rusboost is deployed to classify WCE images. Experiments on a diverse and large scale dataset with 440 K WCE images demonstrate that the proposed approach achieves a promising performance and outperforms the state-of-the-art methods. Moreover, the high sensitivity in detecting hookworms indicates the potential of our approach for future clinical application. PMID- 26886972 TI - Size-Invariant Detection of Cell Nuclei in Microscopy Images. AB - Accurate detection of individual cell nuclei in microscopy images is an essential and fundamental task for many biological studies. In particular, multivariate fluorescence microscopy is used to observe different aspects of cells in cultures. Manual detection of individual cell nuclei by visual inspection is time consuming, and prone to induce subjective bias. This makes automatic detection of cell nuclei essential for large-scale, objective studies of cell cultures. Blur, clutter, bleed-through, imaging noise and touching and partially overlapping nuclei with varying sizes and shapes make automated detection of individual cell nuclei a challenging task using image analysis. In this paper we propose a new automated method for fast and robust detection of individual cell nuclei based on their radial symmetric nature in fluorescence in-situ hybridization (FISH) images obtained via confocal microscopy. The main contributions are two-fold. 1) This work presents a more accurate cell nucleus detection system using the fast radial symmetry transform (FRST). 2) The proposed cell nucleus detection system is robust against most occlusions and variations in size and moderate shape deformations. We evaluate the performance of the proposed algorithm using precision/recall rates, Fbeta-score and root-mean-squared distance (RMSD) and show that our algorithm provides improved detection accuracy compared to existing algorithms. PMID- 26886974 TI - Transurethral Photoacoustic Endoscopy for Prostate Cancer: A Simulation Study. AB - The purpose of this study was to optimize the configuration of a photoacoustic endoscope (PAE) for prostate cancer detection and therapy monitoring. The placement of optical fiber bundles and ultrasound detectors was chosen to maximize the photoacoustic imaging penetration depth. We performed both theoretical calculations and simulations of this optimized PAE configuration on a prostate-sized phantom containing tumor and various photosensitizer concentrations. The optimized configuration of PAE with transurethral light delivery simultaneously increases the imaging penetration depth and improves image quality. Thermal safety, investigated via COMSOL Multiphysics, shows that there is only a 4 mK temperature rise in the urethra during photoacoustic imaging, which will cause no thermal damage. One application of this PAE has been demonstrated for quasi-quantifying photosensitizer concentrations during photodynamic therapy. The sensitivity of the photoacoustic detection for TOOKAD was 0.18 ng/mg at a 763 nm laser wavelength. Results of this study will greatly enhance the potential of prostate PAE for in vivo monitoring of drug delivery and guidance of the laser-induced therapy for future clinical use. PMID- 26886973 TI - Probabilistic Modeling of Imaging, Genetics and Diagnosis. AB - We propose a unified Bayesian framework for detecting genetic variants associated with disease by exploiting image-based features as an intermediate phenotype. The use of imaging data for examining genetic associations promises new directions of analysis, but currently the most widely used methods make sub-optimal use of the richness that these data types can offer. Currently, image features are most commonly selected based on their relevance to the disease phenotype. Then, in a separate step, a set of genetic variants is identified to explain the selected features. In contrast, our method performs these tasks simultaneously in order to jointly exploit information in both data types. The analysis yields probabilistic measures of clinical relevance for both imaging and genetic markers. We derive an efficient approximate inference algorithm that handles the high dimensionality of image and genetic data. We evaluate the algorithm on synthetic data and demonstrate that it outperforms traditional models. We also illustrate our method on Alzheimer's Disease Neuroimaging Initiative data. PMID- 26886975 TI - Automatic Detection of Cerebral Microbleeds From MR Images via 3D Convolutional Neural Networks. AB - Cerebral microbleeds (CMBs) are small haemorrhages nearby blood vessels. They have been recognized as important diagnostic biomarkers for many cerebrovascular diseases and cognitive dysfunctions. In current clinical routine, CMBs are manually labelled by radiologists but this procedure is laborious, time consuming, and error prone. In this paper, we propose a novel automatic method to detect CMBs from magnetic resonance (MR) images by exploiting the 3D convolutional neural network (CNN). Compared with previous methods that employed either low-level hand-crafted descriptors or 2D CNNs, our method can take full advantage of spatial contextual information in MR volumes to extract more representative high-level features for CMBs, and hence achieve a much better detection accuracy. To further improve the detection performance while reducing the computational cost, we propose a cascaded framework under 3D CNNs for the task of CMB detection. We first exploit a 3D fully convolutional network (FCN) strategy to retrieve the candidates with high probabilities of being CMBs, and then apply a well-trained 3D CNN discrimination model to distinguish CMBs from hard mimics. Compared with traditional sliding window strategy, the proposed 3D FCN strategy can remove massive redundant computations and dramatically speed up the detection process. We constructed a large dataset with 320 volumetric MR scans and performed extensive experiments to validate the proposed method, which achieved a high sensitivity of 93.16% with an average number of 2.74 false positives per subject, outperforming previous methods using low-level descriptors or 2D CNNs by a significant margin. The proposed method, in principle, can be adapted to other biomarker detection tasks from volumetric medical data. PMID- 26886977 TI - Skull Optical Clearing Solution for Enhancing Ultrasonic and Photoacoustic Imaging. AB - The performance of photoacoustic microscopy (PAM) degrades due to the turbidity of the skull that introduces attenuation and distortion of both laser and stimulated ultrasound. In this manuscript, we demonstrated that a newly developed skull optical clearing solution (SOCS) could enhance not only the transmittance of light, but also that of ultrasound in the skull in vitro. Thus the photoacoustic signal was effectively elevated, and the relative strength of the artifacts induced by the skull could be suppressed. Furthermore in vivo studies demonstrated that SOCS could drastically enhance the performance of photoacoustic microscopy for cerebral microvasculature imaging. PMID- 26886976 TI - Deep Convolutional Neural Networks for Computer-Aided Detection: CNN Architectures, Dataset Characteristics and Transfer Learning. AB - Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs). CNNs enable learning data-driven, highly representative, hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks. PMID- 26886978 TI - Deep 3D Convolutional Encoder Networks With Shortcuts for Multiscale Feature Integration Applied to Multiple Sclerosis Lesion Segmentation. AB - We propose a novel segmentation approach based on deep 3D convolutional encoder networks with shortcut connections and apply it to the segmentation of multiple sclerosis (MS) lesions in magnetic resonance images. Our model is a neural network that consists of two interconnected pathways, a convolutional pathway, which learns increasingly more abstract and higher-level image features, and a deconvolutional pathway, which predicts the final segmentation at the voxel level. The joint training of the feature extraction and prediction pathways allows for the automatic learning of features at different scales that are optimized for accuracy for any given combination of image types and segmentation task. In addition, shortcut connections between the two pathways allow high- and low-level features to be integrated, which enables the segmentation of lesions across a wide range of sizes. We have evaluated our method on two publicly available data sets (MICCAI 2008 and ISBI 2015 challenges) with the results showing that our method performs comparably to the top-ranked state-of-the-art methods, even when only relatively small data sets are available for training. In addition, we have compared our method with five freely available and widely used MS lesion segmentation methods (EMS, LST-LPA, LST-LGA, Lesion-TOADS, and SLS) on a large data set from an MS clinical trial. The results show that our method consistently outperforms these other methods across a wide range of lesion sizes. PMID- 26886981 TI - Postprocessing Approaches for the Improvement of Cardiac Ultrasound B-Mode Images: A Review. AB - The improvement in the quality and diagnostic value of ultrasound images has been an ongoing research theme for the last three decades. Cardiac ultrasound suffers from a wide range of artifacts such as acoustic noise, shadowing, and enhancement. Most artifacts are a consequence of the interaction of the transmitted ultrasound signals with anatomic structures of the examined body. Structures such as bone, lungs (air), and fat have a direct limiting effect on the quality of the acquired images. Furthermore, physical phenomena such as speckle introduce a granular pattern on the imaged tissue structures that can sometimes obscure fine anatomic detail. Over the years, numerous studies have attempted to address a range of artifacts in medical ultrasound, including cardiac ultrasound B-mode images. This review provides extensive coverage of such attempts identifying their limitations as well as future research opportunities. PMID- 26886979 TI - Estimation of Shear Wave Speed in the Rhesus Macaques' Uterine Cervix. AB - Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and postdates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness, and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least one baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7; multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with five repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical microstructure in both humans and macaques. PMID- 26886982 TI - High-Temperature Piezoelectric Crystals for Acoustic Wave Sensor Applications. AB - In this review paper, nine different types of high-temperature piezoelectric crystals and their sensor applications are overviewed. The important materials' properties of these piezoelectric crystals including dielectric constant, elastic coefficients, piezoelectric coefficients, electromechanical coupling coefficients, and mechanical quality factor are discussed in detail. The determination methods of these physical properties are also presented. Moreover, the growth methods, structures, and properties of these piezoelectric crystals are summarized and compared. Of particular interest are langasite and oxyborate crystals, which exhibit no phase transitions prior to their melting points ~ 1500 degrees C and possess high electrical resistivity, piezoelectric coefficients, and mechanical quality factor at ultrahigh temperature ( ~ 1000 degrees C). Finally, some research results on surface acoustic wave (SAW) and bulk acoustic wave (BAW) sensors developed using this high-temperature piezoelectric crystals are discussed. PMID- 26886980 TI - On System-Dependent Sources of Uncertainty and Bias in Ultrasonic Quantitative Shear-Wave Imaging. AB - Ultrasonic quantitative shear-wave imaging methods have been developed over the last decade to estimate tissue elasticity by measuring the speed of propagating shear waves following acoustic radiation force excitation. This work discusses eight sources of uncertainty and bias arising from ultrasound system-dependent parameters in ultrasound shear-wave speed (SWS) measurements. Each of the eight sources of error is discussed in the context of a linear, isotropic, elastic, homogeneous medium, combining previously reported analyses with Field II simulations, full-wave 2-D acoustic propagation simulations, and experimental studies. Errors arising from both spatial and temporal sources lead to errors in SWS measurements. Arrival time estimation noise, speckle bias, hardware fluctuations, and phase aberration cause uncertainties (variance) in SWS measurements, while pulse repetition frequency (PRF) and beamforming errors, as well as coupling medium sound speed mismatch, cause biases in SWS measurements (accuracy errors). Calibration of the sources of bias is an important step in the development of shear-wave imaging systems. In a well-calibrated system, where the sources of bias are minimized, and averaging over a region of interest (ROI) is employed to reduce the sources of uncertainty, an SWS error can be expected. PMID- 26886983 TI - On the Detectability of Acoustic Waves Induced Following Irradiation by a Radiotherapy Linear Accelerator. AB - Irradiating an object with a megavoltage photon beam generated by a clinical radiotherapy linear accelerator (linac) induces acoustic waves through the photoacoustic effect. The detection and characterization of such acoustic waves has potential applications in radiation therapy dosimetry. The purpose of this work was to gain insight into the properties of such acoustic waves by simulating and experimentally detecting them in a well-defined system consisting of a metal block suspended in a water tank. A novel simulation workflow was developed by combining radiotherapy Monte Carlo and acoustic wave transport simulation techniques. Different set-up parameters such as photon beam energy, metal block depth, metal block width, and metal block material were varied, and the simulated and experimental acoustic waveforms showed the same relative amplitude trends and frequency variations for such setup changes. The simulation platform developed in this work can easily be extended to other irradiation situations, and will be an invaluable tool for developing a radiotherapy dosimetry system based on the detection of the acoustic waves induced following linear accelerator irradiation. PMID- 26886984 TI - Lidar Waveform-Based Analysis of Depth Images Constructed Using Sparse Single Photon Data. AB - This paper presents a new Bayesian model and algorithm used for depth and reflectivity profiling using full waveforms from the time-correlated single photon counting measurement in the limit of very low photon counts. The proposed model represents each Lidar waveform as a combination of a known impulse response, weighted by the target reflectivity, and an unknown constant background, corrupted by Poisson noise. Prior knowledge about the problem is embedded through prior distributions that account for the different parameter constraints and their spatial correlation among the image pixels. In particular, a gamma Markov random field (MRF) is used to model the joint distribution of the target reflectivity, and a second MRF is used to model the distribution of the target depth, which are both expected to exhibit significant spatial correlations. An adaptive Markov chain Monte Carlo algorithm is then proposed to perform Bayesian inference. This algorithm is equipped with a stochastic optimization adaptation mechanism that automatically adjusts the parameters of the MRFs by maximum marginal likelihood estimation. Finally, the benefits of the proposed methodology are demonstrated through a series of experiments using real data. PMID- 26886985 TI - Effective Five Directional Partial Derivatives-Based Image Smoothing and a Parallel Structure Design. AB - Image smoothing has been used for image segmentation, image reconstruction, object classification, and 3D content generation. Several smoothing approaches have been used at the pre-processing step to retain the critical edge, while removing noise and small details. However, they have limited performance, especially in removing small details and smoothing discrete regions. Therefore, to provide fast and accurate smoothing, we propose an effective scheme that uses a weighted combination of the gradient, Laplacian, and diagonal derivatives of a smoothed image. In addition, to reduce computational complexity, we designed and implemented a parallel processing structure for the proposed scheme on a graphics processing unit (GPU). For an objective evaluation of the smoothing performance, the images were linearly quantized into several layers to generate experimental images, and the quantized images were smoothed using several methods for reconstructing the smoothly changed shape and intensity of the original image. Experimental results showed that the proposed scheme has higher objective scores and better successful smoothing performance than similar schemes, while preserving and removing critical and trivial details, respectively. For computational complexity, the proposed smoothing scheme running on a GPU provided 18 and 16 times lower complexity than the proposed smoothing scheme running on a CPU and the L0-based smoothing scheme, respectively. In addition, a simple noise reduction test was conducted to show the characteristics of the proposed approach; it reported that the presented algorithm outperforms the state-of-the art algorithms by more than 5.4 dB. Therefore, we believe that the proposed scheme can be a useful tool for efficient image smoothing. PMID- 26886986 TI - Texture Classification Using Dense Micro-Block Difference. AB - This paper is devoted to the problem of texture classification. Motivated by recent advancements in the field of compressive sensing and keypoints descriptors, a set of novel features called dense micro-block difference (DMD) is proposed. These features provide highly descriptive representation of image patches by densely capturing the granularities at multiple scales and orientations. Unlike most of the earlier work on local features, the DMD does not involve any quantization, thus retaining the complete information. We demonstrate that the DMD have dimensionality much lower than Scale Invariant Feature Transform (SIFT) and can be computed using integral image much faster than SIFT. The proposed features are encoded using the Fisher vector method to obtain an image descriptor, which considers high-order statistics. The proposed image representation is combined with the linear support vector machine classifier. Extensive experiments are conducted on five texture data sets (KTH-TIPS, UMD, KTH TIPS-2a, Brodatz, and Curet) using standard protocols. The results demonstrate that our approach outperforms the state-of-the-art in texture classification. PMID- 26886987 TI - Unsupervised Co-Segmentation for Indefinite Number of Common Foreground Objects. AB - Co-segmentation addresses the problem of simultaneously extracting the common targets appeared in multiple images. Multiple common targets involved object co segmentation problem, which is very common in reality, has been a new research hotspot recently. In this paper, an unsupervised object co-segmentation method for indefinite number of common targets is proposed. This method overcomes the inherent limitation of traditional proposal selection-based methods for multiple common targets involved images while retaining their original advantages for objects extracting. For each image, the proposed multi-search strategy extracts each target individually and an adaptive decision criterion is raised to give each candidate a reliable judgment automatically, i.e., target or non-target. The comparison experiments conducted on public data sets iCoseg, MSRC, and a more challenging data set Coseg-INCT demonstrate the superior performance of the proposed method. PMID- 26886988 TI - Statistical Performance Analysis of a Fast Super-Resolution Technique Using Noisy Translations. AB - The registration process is a key step for super-resolution (SR) reconstruction. More and more devices permit to overcome this bottleneck using a controlled positioning system, e.g., sensor shifting using a piezoelectric stage. This makes possible to acquire multiple images of the same scene at different controlled positions. Then, a fast SR algorithm can be used for efficient SR reconstruction. In this case, the optimal use of r(2) images for a resolution enhancement factor r is generally not enough to obtain satisfying results due to the random inaccuracy of the positioning system. Thus, we propose to take several images around each reference position. We study the error produced by the SR algorithm due to spatial uncertainty as a function of the number of images per position. We obtain a lower bound on the number of images that is necessary to ensure a given error upper bound with probability higher than some desired confidence level. Such results give precious hints to the design of SR systems. PMID- 26886989 TI - The Semi-Variogram and Spectral Distortion Measures for Image Texture Retrieval. AB - Semi-variogram estimators and distortion measures of signal spectra are utilized in this paper for image texture retrieval. On the use of the complete Brodatz database, most high retrieval rates are reportedly based on multiple features and the combinations of multiple algorithms, while the classification using single features is still a challenge to the retrieval of diverse texture images. The semi-variogram, which is theoretically sound and the cornerstone of spatial statistics, has the characteristics shared between true randomness and complete determinism and, therefore, can be used as a useful tool for both the structural and statistical analysis of texture images. Meanwhile, spectral distortion measures derived from the theory of linear predictive coding provide a rigorously mathematical model for signal-based similarity matching and have been proven useful for many practical pattern classification systems. Experimental results obtained from testing the proposed approach using the complete Brodatz database, and the the University of Illinois at Urbana-Champaign texture database suggests the effectiveness of the proposed approach as a single-feature-based dissimilarity measure for real-time texture retrieval. PMID- 26886990 TI - Regularization Strategies for Discontinuity-Preserving Optical Flow Methods. AB - The aim of this paper is to study several strategies for the preservation of flow discontinuities in variational optical flow methods. We analyze the combination of robust functionals and diffusion tensors in the smoothness assumption. Our study includes the use of tensors based on decreasing functions, which has shown to provide good results. However, it presents several limitations and usually does not perform better than other basic approaches. It typically introduces instabilities in the computed motion fields in the form of independent blobs of vectors with large magnitude. We propose two alternatives to overcome these drawbacks: first, a simple approach that combines the decreasing function with a minimum isotropic smoothing, and second, a method that looks for the best parameter configuration that preserves the important motion contours and avoid instabilities. It relies on the input images and the regularization parameter. It is fully automatic, providing a near-optimal value for many sequences, as shown in the experiments. Both proposals allow to detect the contours of the motion field and produce more stable solutions for a large range of parameters. In the experimental results, we present a detailed study and comparison of the different strategies. PMID- 26886991 TI - Joint Cross-Range Scaling and 3D Geometry Reconstruction of ISAR Targets Based on Factorization Method. AB - Traditionally, the factorization method is applied to reconstruct the 3D geometry of a target from its sequential inverse synthetic aperture radar images. However, this method requires performing cross-range scaling to all the sub-images and thus has a large computational burden. To tackle this problem, this paper proposes a novel method for joint cross-range scaling and 3D geometry reconstruction of steadily moving targets. In this method, we model the equivalent rotational angular velocity (RAV) by a linear polynomial with time, and set its coefficients randomly to perform sub-image cross-range scaling. Then, we generate the initial trajectory matrix of the scattering centers, and solve the 3D geometry and projection vectors by the factorization method with relaxed constraints. After that, the coefficients of the polynomial are estimated from the projection vectors to obtain the RAV. Finally, the trajectory matrix is re scaled using the estimated rotational angle, and accurate 3D geometry is reconstructed. The two major steps, i.e., the cross-range scaling and the factorization, are performed repeatedly to achieve precise 3D geometry reconstruction. Simulation results have proved the effectiveness and robustness of the proposed method. PMID- 26886992 TI - Non-Parametric Blur Map Regression for Depth of Field Extension. AB - Real camera systems have a limited depth of field (DOF) which may cause an image to be degraded due to visible misfocus or too shallow DOF. In this paper, we present a blind deblurring pipeline able to restore such images by slightly extending their DOF and recovering sharpness in regions slightly out of focus. To address this severely ill-posed problem, our algorithm relies first on the estimation of the spatially varying defocus blur. Drawing on local frequency image features, a machine learning approach based on the recently introduced regression tree fields is used to train a model able to regress a coherent defocus blur map of the image, labeling each pixel by the scale of a defocus point spread function. A non-blind spatially varying deblurring algorithm is then used to properly extend the DOF of the image. The good performance of our algorithm is assessed both quantitatively, using realistic ground truth data obtained with a novel approach based on a plenoptic camera, and qualitatively with real images. PMID- 26886993 TI - Data-Driven Soft Decoding of Compressed Images in Dual Transform-Pixel Domain. AB - In the large body of research literature on image restoration, very few papers were concerned with compression-induced degradations, although in practice, the most common cause of image degradation is compression. This paper presents a novel approach to restoring JPEG-compressed images. The main innovation is in the approach of exploiting residual redundancies of JPEG code streams and sparsity properties of latent images. The restoration is a sparse coding process carried out jointly in the DCT and pixel domains. The prowess of the proposed approach is directly restoring DCT coefficients of the latent image to prevent the spreading of quantization errors into the pixel domain, and at the same time, using online machine-learned local spatial features to regulate the solution of the underlying inverse problem. Experimental results are encouraging and show the promise of the new approach in significantly improving the quality of DCT-coded images. PMID- 26886994 TI - CASAIR: Content and Shape-Aware Image Retargeting and Its Applications. AB - This paper proposes a novel image-retargeting algorithm that can retarget images to a large family of non-rectangular shapes. Specifically, we study image retargeting from a broader perspective that includes the content as well as the shape of an image, and the proposed content and shape-aware image-retargeting (CASAIR) algorithm is driven by the dual objectives of image content preservation and image domain transformation, with the latter defined by an application specific target shape. The algorithm is based on the idea of seam segment carving that successively removes low-cost seam segments from the image to simultaneously achieve the two objectives, with the selection of seam segments determined by a cost function incorporating inputs from image content and target shape. To provide a complete characterization of shapes that can be obtained using CASAIR, we introduce the notion of bhv-convex shapes, and we show that bhv-convex shapes are precisely the family of shapes that can be retargeted to by CASAIR. The proposed algorithm is simple in both its design and implementation, and in practice, it offers an efficient and effective retargeting platform that provides its users with considerable flexibility in choosing target shapes. To demonstrate the potential of CASAIR for broadening the application scope of image retargeting, this paper also proposes a smart camera-projector system that incorporates CASAIR. In the context of ubiquitous display, CASAIR equips the camera-projector system with the capability of retargeting images online in order to maximize the quality and fidelity of the displayed images whenever the situation demands. PMID- 26886995 TI - LBP-Based Segmentation of Defocus Blur. AB - Defocus blur is extremely common in images captured using optical imaging systems. It may be undesirable, but may also be an intentional artistic effect, thus it can either enhance or inhibit our visual perception of the image scene. For tasks, such as image restoration and object recognition, one might want to segment a partially blurred image into blurred and non-blurred regions. In this paper, we propose a sharpness metric based on local binary patterns and a robust segmentation algorithm to separate in- and out-of-focus image regions. The proposed sharpness metric exploits the observation that most local image patches in blurry regions have significantly fewer of certain local binary patterns compared with those in sharp regions. Using this metric together with image matting and multi-scale inference, we obtained high-quality sharpness maps. Tests on hundreds of partially blurred images were used to evaluate our blur segmentation algorithm and six comparator methods. The results show that our algorithm achieves comparative segmentation results with the state of the art and have big speed advantage over the others. PMID- 26886997 TI - Evaluation of the Achilles Ankle Exoskeleton. AB - This paper evaluates the Achilles exoskeleton. The exoskeleton is intended to provide push-off assistance for healthy subjects during walking. The assistance is provided by a series elastic actuator that has been optimized to provide maximal push-off power. The paper presents the control method of the exoskeleton and the evaluation of the exoskeleton. PMID- 26886998 TI - Genome-Wide Search for Translated Upstream Open Reading Frames in Arabidopsis Thaliana. AB - Upstream open reading frames (uORFs) are open reading frames that occur within the 5' UTR of an mRNA. uORFs have been found in many organisms. They play an important role in gene regulation, cell development, and in various metabolic processes. It is believed that translated uORFs reduce the translational efficiency of the main coding region. However, only few uORFs are experimentally characterized. In this paper, we use ribosome footprinting together with a semi supervised approach based on stacking classification models to identify translated uORFs in Arabidopsis thaliana. Our approach identified 5360 potentially translated uORFs in 2051 genes. GO terms enriched in genes with translated uORFs include catalytic activity, binding, transferase activity, phosphotransferase activity, kinase activity, and transcription regulator activity. The reported uORFs occur with a higher frequency in multi-isoform genes, and some uORFs are affected by alternative transcript start sites or alternative splicing events. Association rule mining revealed sequence features associated with the translation status of the uORFs. We hypothesize that uORF translation is a complex process that might be regulated by multiple factors. The identified uORFs are available online at:https://www.dropbox.com/sh/zdutupedxafhly8/AABFsdNR5zDfiozB7B4igFcja?dl=0. This paper is the extended version of our research presented at ISBRA 2015. PMID- 26886999 TI - Kinesin-1 Expressed in Insect Cells Improves Microtubule in Vitro Gliding Performance, Long-Term Stability and Guiding Efficiency in Nanostructures. AB - The cytoskeletal motor protein kinesin-1 has been successfully used for many nanotechnological applications. Most commonly, these applications use a gliding assay geometry where substrate-attached motor proteins propel microtubules along the surface. So far, this assay has only been shown to run undisturbed for up to 8 h. Longer run times cause problems like microtubule shrinkage, microtubules getting stuck and slowing down. This is particularly problematic in nanofabricated structures where the total number of microtubules is limited and detachment at the structure walls causes additional microtubule loss. We found that many of the observed problems are caused by the bacterial expression system, which has so far been used for nanotechnological applications of kinesin-1. We strive to enable the use of this motor system for more challenging nanotechnological applications where long-term stability and/or reliable guiding in nanostructures is required. Therefore, we established the expression and purification of kinesin-1 in insect cells which results in improved purity and- more importantly--long-term stability > 24 h and guiding efficiencies of > 90% in lithographically defined nanostructures. PMID- 26887000 TI - Robustness Analysis of a Geant4-GATE Simulator for Nanoradiosensitizers Characterization. AB - The increase of computational environments dedicated to the simulation of nanoparticles (NP)-X-Rays interactions has opened new perspectives in computer aided-design of nanostructured materials for biomedical applications. Several published studies have shown a crucial need of standardization of these numerical simulations. That is why, a robustness multivariate analysis was performed in this paper. A gold nanoparticle (GNP) of 100 nm diameter was selected as a standard nanosystem activated by a X-ray source placed just below the NP. Two response variables were examined: the dose enhancement in seven different spatial regions of interest around the NP and the duration of the experiments. Nine factors were pre-identified as potentially critical. A Plackett-Burman design of numerical experiments was applied to estimate and test the effects of each simulation factors on the examined responses. Four factors-the working volume, the spatial resolution, the spatial cutoff, and the computational mode (parallelization)-do not significantly affect the dose deposition results and none except the last one may reduce the computational duration. The energy cutoff may cause significant variations of the dose enhancement in some specific regions of interest: the higher the cutoff, the closer the secondary particles will stop from the GNP. By contrast, the Auger effect as well as the choice of the physical medium and the fluence level clearly appear as critical simulation parameters. Consequently, these four factors may be compulsory examined before comparing and interpreting any simulation results coming from different simulation sessions. PMID- 26887001 TI - Unconstrained Diameters for Deep Coalescence. AB - The minimizing-deep-coalescence (MDC) approach infers a median (species) tree for a given set of gene trees under the deep coalescence cost. This cost accounts for the minimum number of deep coalescences needed to reconcile a gene tree with a species tree where the leaf-genes are mapped to the leaf-species through a function called leaf labeling. In order to better understand the MDC approach we investigate here the diameter of a gene tree, which is an important property of the deep coalescence cost. This diameter is the maximal deep coalescence costs for a given gene tree under all leaf labelings for each possible species tree topology. While we prove that this diameter is generally infinite, this result relies on the diameter's unrealistic assumption that species trees can be of infinite size. Providing a more practical definition, we introduce a natural extension of the gene tree diameter that constrains the species tree size by a given constant. For this new diameter, we describe an exact formula, present a complete classification of the trees yielding this diameter, derive formulas for its mean and variance, and demonstrate its ability using comparative studies. PMID- 26887002 TI - A New Scheme to Characterize and Identify Protein Ubiquitination Sites. AB - Protein ubiquitination, involving the conjugation of ubiquitin on lysine residue, serves as an important modulator of many cellular functions in eukaryotes. Recent advancements in proteomic technology have stimulated increasing interest in identifying ubiquitination sites. However, most computational tools for predicting ubiquitination sites are focused on small-scale data. With an increasing number of experimentally verified ubiquitination sites, we were motivated to design a predictive model for identifying lysine ubiquitination sites for large-scale proteome dataset. This work assessed not only single features, such as amino acid composition (AAC), amino acid pair composition (AAPC) and evolutionary information, but also the effectiveness of incorporating two or more features into a hybrid approach to model construction. The support vector machine (SVM) was applied to generate the prediction models for ubiquitination site identification. Evaluation by five-fold cross-validation showed that the SVM models learned from the combination of hybrid features delivered a better prediction performance. Additionally, a motif discovery tool, MDDLogo, was adopted to characterize the potential substrate motifs of ubiquitination sites. The SVM models integrating the MDDLogo-identified substrate motifs could yield an average accuracy of 68.70 percent. Furthermore, the independent testing result showed that the MDDLogo-clustered SVM models could provide a promising accuracy (78.50 percent) and perform better than other prediction tools. Two cases have demonstrated the effective prediction of ubiquitination sites with corresponding substrate motifs. PMID- 26887003 TI - A Flexible Computational Framework Using R and Map-Reduce for Permutation Tests of Massive Genetic Analysis of Complex Traits. AB - In quantitative trait locus (QTL) mapping significance of putative QTL is often determined using permutation testing. The computational needs to calculate the significance level are immense, 104 up to 108 or even more permutations can be needed. We have previously introduced the PruneDIRECT algorithm for multiple QTL scan with epistatic interactions. This algorithm has specific strengths for permutation testing. Here, we present a flexible, parallel computing framework for identifying multiple interacting QTL using the PruneDIRECT algorithm which uses the map-reduce model as implemented in Hadoop. The framework is implemented in R, a widely used software tool among geneticists. This enables users to rearrange algorithmic steps to adapt genetic models, search algorithms, and parallelization steps to their needs in a flexible way. Our work underlines the maturity of accessing distributed parallel computing for computationally demanding bioinformatics applications through building workflows within existing scientific environments. We investigate the PruneDIRECT algorithm, comparing its performance to exhaustive search and DIRECT algorithm using our framework on a public cloud resource. We find that PruneDIRECT is vastly superior for permutation testing, and perform 2 *105 permutations for a 2D QTL problem in 15 hours, using 100 cloud processes. We show that our framework scales out almost linearly for a 3D QTL search. PMID- 26887004 TI - A Resolution of the Static Formulation Question for the Problem of Computing the History Bound. AB - Evolutionary data has been traditionally modeled via phylogenetic trees; however, branching alone cannot model conflicting phylogenetic signals, so networks are used instead. Ancestral recombination graphs (ARGs) are used to model the evolution of incompatible sets of SNP data, allowing each site to mutate only once. The model often aims to minimize the number of recombinations. Similarly, incompatible cluster data can be represented by a reticulation network that minimizes reticulation events. The ARG literature has traditionally been disjoint from the reticulation network literature. By building on results from the reticulation network literature, we resolve an open question of interest to the ARG community. We explicitly prove that the History Bound, a lower bound on the number of recombinations in an ARG for a binary matrix, which was previously only defined procedurally, is equal to the minimum number of reticulation nodes in a network for the corresponding cluster data. To facilitate the proof, we give an algorithm that constructs this network using intermediate values from the procedural History Bound definition. We then develop a top-down algorithm for computing the History Bound, which has the same worst-case runtime as the known dynamic program, and show that it is likely to run faster in typical cases. PMID- 26887005 TI - Genome-Wide Semi-Automated Annotation of Transporter Systems. AB - Usually, transport reactions are added to genome-scale metabolic models (GSMMs) based on experimental data and literature. This approach does not allow associating specific genes with transport reactions, which impairs the ability of the model to predict effects of gene deletions. Novel methods for systematic genome-wide transporter functional annotation and their integration into GSMMs are therefore necessary. In this work, an automatic system to detect and classify all potential membrane transport proteins for a given genome and integrate the related reactions into GSMMs is proposed, based on the identification and classification of genes that encode transmembrane proteins. The Transport Reactions Annotation and Generation (TRIAGE) tool identifies the metabolites transported by each transmembrane protein and its transporter family. The localization of the carriers is also predicted and, consequently, their action is confined to a given membrane. The integration of the data provided by TRIAGE with highly curated models allowed the identification of new transport reactions. TRIAGE is included in the new release of merlin, a software tool previously developed by the authors, which expedites the GSMM reconstruction processes. PMID- 26887006 TI - Searching Genome-Wide Multi-Locus Associations for Multiple Diseases Based on Bayesian Inference. AB - Taking the advantage of high-throughput single nucleotide polymorphism (SNP) genotyping technology, large genome-wide association studies (GWASs) have been considered to hold promise for unraveling complex relationships between genotypes and phenotypes. Current multi-locus-based methods are insufficient to detect interactions with diverse genetic effects on multifarious diseases. Also, statistic tests for high-order epistasis ( >= 2 SNPs) raise huge computational and analytical challenges because the computation increases exponentially as the growth of the cardinality of SNPs combinations. In this paper, we provide a simple, fast and powerful method, named DAM, using Bayesian inference to detect genome-wide multi-locus epistatic interactions in multiple diseases. Experimental results on simulated data demonstrate that our method is powerful and efficient. We also apply DAM on two GWAS datasets from WTCCC, i.e., Rheumatoid Arthritis and Type 1 Diabetes, and identify some novel findings. Therefore, we believe that our method is suitable and efficient for the full-scale analysis of multi-disease related interactions in GWASs. PMID- 26887007 TI - Extending and Applying Spartan to Perform Temporal Sensitivity Analyses for Predicting Changes in Influential Biological Pathways in Computational Models. AB - Through integrating real time imaging, computational modelling, and statistical analysis approaches, previous work has suggested that the induction of and response to cell adhesion factors is the key initiating pathway in early lymphoid tissue development, in contrast to the previously accepted view that the process is triggered by chemokine mediated cell recruitment. These model derived hypotheses were developed using spartan, an open-source sensitivity analysis toolkit designed to establish and understand the relationship between a computational model and the biological system that model captures. Here, we extend the functionality available in spartan to permit the production of statistical analyses that contrast the behavior exhibited by a computational model at various simulated time-points, enabling a temporal analysis that could suggest whether the influence of biological mechanisms changes over time. We exemplify this extended functionality by using the computational model of lymphoid tissue development as a time-lapse tool. By generating results at twelve hour intervals, we show how the extensions to spartan have been used to suggest that lymphoid tissue development could be biphasic, and predict the time-point when a switch in the influence of biological mechanisms might occur. PMID- 26887008 TI - Optimal Landmark Selection for Registration of 4D Confocal Image Stacks in Arabidopsis. AB - Technologically advanced imaging techniques have allowed us to generate and study the internal part of a tissue over time by capturing serial optical images that contain spatio-temporal slices of hundreds of tightly packed cells. Image registration of such live-imaging datasets of developing multicelluar tissues is one of the essential components of all image analysis pipelines. In this paper, we present a fully automated 4D(X-Y-Z-T) registration method of live imaging stacks that takes care of both temporal and spatial misalignments. We present a novel landmark selection methodology where the shape features of individual cells are not of high quality and highly distinguishable. The proposed registration method finds the best image slice correspondence from consecutive image stacks to account for vertical growth in the tissue and the discrepancy in the choice of the starting focal point. Then, it uses local graph-based approach to automatically find corresponding landmark pairs, and finally the registration parameters are used to register the entire image stack. The proposed registration algorithm combined with an existing tracking method is tested on multiple image stacks of tightly packed cells of Arabidopsis shoot apical meristem and the results show that it significantly improves the accuracy of cell lineages and division statistics. PMID- 26887009 TI - Transductive Learning for Multi-Label Protein Subchloroplast Localization Prediction. AB - Predicting the localization of chloroplast proteins at the sub-subcellular level is an essential yet challenging step to elucidate their functions. Most of the existing subchloroplast localization predictors are limited to predicting single location proteins and ignore the multi-location chloroplast proteins. While recent studies have led to some multi-location chloroplast predictors, they usually perform poorly. This paper proposes an ensemble transductive learning method to tackle this multi-label classification problem. Specifically, given a protein in a dataset, its composition-based sequence information and profile based evolutionary information are respectively extracted. These two kinds of features are respectively compared with those of other proteins in the dataset. The comparisons lead to two similarity vectors which are weighted-combined to constitute an ensemble feature vector. A transductive learning model based on the least squares and nearest neighbor algorithms is proposed to process the ensemble features. We refer to the resulting predictor to as EnTrans-Chlo. Experimental results on a stringent benchmark dataset and a novel dataset demonstrate that EnTrans-Chlo significantly outperforms state-of-the-art predictors and particularly gains more than 4% (absolute) improvement on the overall actual accuracy. For readers' convenience, EnTrans-Chlo is freely available online at http://bioinfo.eie.polyu.edu.hk/EnTransChloServer/. PMID- 26887010 TI - Enhancing the Prediction of Transmembrane beta-Barrel Segments with Chain Learning and Feature Sparse Representation. AB - Transmembrane beta-barrels (TMBs) are one important class of membrane proteins that play crucial functions in the cell. Membrane proteins are difficult wet-lab targets of structural biology, which call for accurate computational prediction approaches. Here, we developed a novel method named MemBrain-TMB to predict the spanning segments of transmembrane beta-barrel from amino acid sequence. MemBrain TMB is a statistical machine learning-based model, which is constructed using a new chain learning algorithm with input features encoded by the image sparse representation approach. We considered the relative status information between neighboring residues for enhancing the performance, and the matrix of features was translated into feature image by sparse coding algorithm for noise and dimension reduction. To deal with the diverse loop length problem, we applied a dynamic threshold method, which is particularly useful for enhancing the recognition of short loops and tight turns. Our experiments demonstrate that the new protocol designed in MemBrain-TMB effectively helps improve prediction performance. PMID- 26887011 TI - Algorithms and Complexity Results for Genome Mapping Problems. AB - Genome mapping algorithms aim at computing an ordering of a set of genomic markers based on local ordering information such as adjacencies and intervals of markers. In most genome mapping models, markers are assumed to occur uniquely in the resulting map. We introduce algorithmic questions that consider repeats, i.e., markers that can have several occurrences in the resulting map. We show that, provided with an upper bound on the copy number of repeated markers and with intervals that span full repeat copies, called repeat spanning intervals, the problem of deciding if a set of adjacencies and repeat spanning intervals admits a genome representation is tractable if the target genome can contain linear and/or circular chromosomal fragments. We also show that extracting a maximum cardinality or weight subset of repeat spanning intervals given a set of adjacencies that admits a genome realization is NP-hard but fixed-parameter tractable in the maximum copy number and the number of adjacent repeats, and tractable if intervals contain a single repeated marker. PMID- 26887012 TI - Quantitative Laughter Detection, Measurement, and Classification-A Critical Survey. AB - The study of human nonverbal social behaviors has taken a more quantitative and computational approach in recent years due to the development of smart interfaces and virtual agents or robots able to interact socially. One of the most interesting nonverbal social behaviors, producing a characteristic vocal signal, is laughing. Laughter is produced in several different situations: in response to external physical, cognitive, or emotional stimuli; to negotiate social interactions; and also, pathologically, as a consequence of neural damage. For this reason, laughter has attracted researchers from many disciplines. A consequence of this multidisciplinarity is the absence of a holistic vision of this complex behavior: the methods of analysis and classification of laughter, as well as the terminology used, are heterogeneous; the findings sometimes contradictory and poorly documented. This survey aims at collecting and presenting objective measurement methods and results from a variety of different studies in different fields, to contribute to build a unified model and taxonomy of laughter. This could be successfully used for advances in several fields, from artificial intelligence and human-robot interaction to medicine and psychiatry. PMID- 26887013 TI - Anticipatory Vibrotactile Cueing Facilitates Grip Force Adjustment during Perturbative Loading. AB - Grip force applied to an object held between the thumb and index finger is automatically and unconsciously adjusted upon perception of an external disturbance to the object. Typically, this adjustment occurs within approximately 100 ms. Here, we investigated the effect of anticipatory vibrotactile cues prior to a perturbative force, which the central nervous system may use for rapid grip re-stabilization. We asked participants to grip and hold an instrumented, actuated handle between the thumb and index finger. Under computer control, the handle could suddenly be pulled away from a static grip and could independently provide vibration to the gripping fingers. The mean latency of corrective motor action was 139 ms. When vibrotactile stimulation was applied 50 ms before application of tractive force, the latency was reduced to 117 ms, whereas the mean latency of the conscious response to vibrotactile stimuli alone was 229 ms. This suggests that vibrotactile stimulation can influence reflex-like actions. We also examined the effects of anticipatory cues using a set of perturbative loads with different rising rates. As expected, facilitation of grip force adjustment was observed for moderate loads. In contrast, anticipatory cues had an insignificant effect on rapid loads that evoked an adjustment within 60-80 ms, which approaches the minimum latency of human grip adjustment. Understanding the facilitative effects of anticipatory cues on human reactive grip can aid the development of human-machine interfaces to enhance human behavior. PMID- 26887014 TI - Pinning Impulsive Synchronization of Reaction-Diffusion Neural Networks With Time Varying Delays. AB - This paper investigates the exponential synchronization of reaction-diffusion neural networks with time-varying delays subject to Dirichlet boundary conditions. A novel type of pinning impulsive controllers is proposed to synchronize the reaction-diffusion neural networks with time-varying delays. By applying the Lyapunov functional method, sufficient verifiable conditions are constructed for the exponential synchronization of delayed reaction-diffusion neural networks with large and small delay sizes. It is shown that synchronization can be realized by pinning impulsive control of a small portion of neurons of the network; the technique used in this paper is also applicable to reaction-diffusion networks with Neumann boundary conditions. Numerical examples are presented to demonstrate the effectiveness of the theoretical results. PMID- 26887015 TI - High-Performance Consensus Control in Networked Systems With Limited Bandwidth Communication and Time-Varying Directed Topologies. AB - Communication data rates and energy constraints are two important factors that have to be considered in the coordination control of multiagent networks. Although some encoder-decoder-based consensus protocols are available, there still exists a fundamental theoretical problem: how can we further reduce the update rate of control input for each agent without the changing consensus performance? In this paper, we consider the problem of average consensus over directed and time-varying digital networks of discrete-time first-order multiagent systems with limited communication data transmission rates. Each agent has a real-valued state but can only exchange binary symbolic sequence with its neighbors due to bandwidth constraints. A class of novel event-triggered dynamic encoding and decoding algorithms is proposed, based on which a kind of consensus protocol is presented. Moreover, we develop a scheme to select the numbers of time-varying quantization levels for each connected communication channel in the time-varying directed topologies at each time step. The analytical relation among system and network parameters is characterized explicitly. It is shown that the asymptotic convergence rate is related to the scale of the network, the number of quantization levels, the system parameter, and the network structure. It is also found that under the designed event-triggered protocol, for a directed and time varying digital network, which uniformly contains a spanning tree over a time interval, the average consensus can be achieved with an exponential convergence rate based on merely 1-b information exchange between each pair of adjacent agents at each time step. PMID- 26887016 TI - HEp-2 Cell Image Classification With Deep Convolutional Neural Networks. AB - Efficient Human Epithelial-2 cell image classification can facilitate the diagnosis of many autoimmune diseases. This paper proposes an automatic framework for this classification task, by utilizing the deep convolutional neural networks (CNNs) which have recently attracted intensive attention in visual recognition. In addition to describing the proposed classification framework, this paper elaborates several interesting observations and findings obtained by our investigation. They include the important factors that impact network design and training, the role of rotation-based data augmentation for cell images, the effectiveness of cell image masks for classification, and the adaptability of the CNN-based classification system across different datasets. Extensive experimental study is conducted to verify the above findings and compares the proposed framework with the well-established image classification models in the literature. The results on benchmark datasets demonstrate that 1) the proposed framework can effectively outperform existing models by properly applying data augmentation, 2) our CNN-based framework has excellent adaptability across different datasets, which is highly desirable for cell image classification under varying laboratory settings. Our system is ranked high in the cell image classification competition hosted by ICPR 2014. PMID- 26887017 TI - A Hierarchical Classification and Segmentation Scheme for Processing Sensor Data. AB - Detecting short-duration events from continuous sensor signals is a significant challenge in the domain of wearable devices and health monitoring systems. Time series segmentation refers to the challenge of subdividing a continuous stream of data into discrete windows, which can be individually processed using statistical classifiers or other algorithms. In this paper, we propose an algorithm for segmenting time-series signals and detecting short-duration data in the domain of lightweight embedded systems with real-time constraints. First, we demonstrate an approach for signal segmentation using a simple binary classifier. Next, we show how a novel two-stage classification algorithm can reduce computational overhead compared to a single-stage approach. Our proposed scheme is benchmarked using an audio-based nutrition-monitoring case study. PMID- 26887018 TI - Real-Time Hypoxia Prediction Using Decision Fusion. AB - Humans who operate in high altitudes for prolonged durations often suffer from hypoxia. The commencement of physiological and cognitive changes due to the onset of hypoxia may not be immediately apparent to the exposed individual. These changes can go unrecognized for minutes and even hours and may lead to serious performance degradation or complete incapacitation. A dynamic system capable of monitoring and detecting decreased physiologic states due to the onset of hypoxia has the potential to prevent adverse outcomes. In this study, we develop a real time hypoxia monitoring system based on a parallel M -ary decision fusion architecture. Blood oxygen saturation levels and altitude readings are the inputs and estimates of the level of hypoxia are the outputs. We develop new temporal evolution models for blood oxygen saturation and functional impairment with respect to varying altitude. The proposed models enable accurate tracking of various hypoxia levels based on the duration of stay of the subject at an altitude. Using a Bayesian decision-making formulation, the system generates global estimates of the degree of hypoxia. The detection system is tested against synthetic and real datasets to demonstrate applicability and accuracy. PMID- 26887019 TI - Adjustable Parameter-Based Distributed Fault Estimation Observer Design for Multiagent Systems With Directed Graphs. AB - In this paper, a novel adjustable parameter (AP)-based distributed fault estimation observer (DFEO) is proposed for multiagent systems (MASs) with the directed communication topology. First, a relative output estimation error is defined based on the communication topology of MASs. Then a DFEO with AP is constructed with the purpose of improving the accuracy of fault estimation. Based on H infinity and H 2 with pole placement, multiconstrained design is given to calculate the gain of DFEO. Finally, simulation results are presented to illustrate the feasibility and effectiveness of the proposed DFEO design with AP. PMID- 26887020 TI - $H_?infty $ Control for 2-D Fuzzy Systems With Interval Time-Varying Delays and Missing Measurements. AB - In this paper, we consider the Hinfinity control problem for a class of 2-D Takagi-Sugeno fuzzy described by the second Fornasini-Machesini local state-space model with time-delays and missing measurements. The state delays are allowed to be time-varying within a known interval. The measurement output is subject to randomly intermittent packet dropouts governed by a random sequence satisfying the Bernoulli distribution. The purpose of the addressed problem is to design an output-feedback controller such that the closed-loop system is globally asymptotically stable in the mean square and the prescribed Hinfinity performance index is satisfied. By employing a combination of the intensive stochastic analysis and the free weighting matrix method, several delay-range-dependent sufficient conditions are presented that guarantee the existence of the desired controllers for all possible time-delays and missing measurements. The explicit expressions of such controllers are derived by means of the solution to a class of convex optimization problems that can be solved via standard software packages. Finally, a numerical simulation example is given to demonstrate the applicability of the proposed control scheme. PMID- 26887021 TI - Evolving Transcription Factor Binding Site Models From Protein Binding Microarray Data. AB - Protein binding microarray (PBM) is a high-throughput platform that can measure the DNA binding preference of a protein in a comprehensive and unbiased manner. In this paper, we describe the PBM motif model building problem. We apply several evolutionary computation methods and compare their performance with the interior point method, demonstrating their performance advantages. In addition, given the PBM domain knowledge, we propose and describe a novel method called kmerGA which makes domain-specific assumptions to exploit PBM data properties to build more accurate models than the other models built. The effectiveness and robustness of kmerGA is supported by comprehensive performance benchmarking on more than 200 datasets, time complexity analysis, convergence analysis, parameter analysis, and case studies. To demonstrate its utility further, kmerGA is applied to two real world applications: 1) PBM rotation testing and 2) ChIP-Seq peak sequence prediction. The results support the biological relevance of the models learned by kmerGA, and thus its real world applicability. PMID- 26887022 TI - A Hierarchical Auction-Based Mechanism for Real-Time Resource Allocation in Cloud Robotic Systems. AB - Cloud computing enables users to share computing resources on-demand. The cloud computing framework cannot be directly mapped to cloud robotic systems with ad hoc networks since cloud robotic systems have additional constraints such as limited bandwidth and dynamic structure. However, most multirobotic applications with cooperative control adopt this decentralized approach to avoid a single point of failure. Robots need to continuously update intensive data to execute tasks in a coordinated manner, which implies real-time requirements. Thus, a resource allocation strategy is required, especially in such resource-constrained environments. This paper proposes a hierarchical auction-based mechanism, namely link quality matrix (LQM) auction, which is suitable for ad hoc networks by introducing a link quality indicator. The proposed algorithm produces a fast and robust method that is accurate and scalable. It reduces both global communication and unnecessary repeated computation. The proposed method is designed for firm real-time resource retrieval for physical multirobot systems. A joint surveillance scenario empirically validates the proposed mechanism by assessing several practical metrics. The results show that the proposed LQM auction outperforms state-of-the-art algorithms for resource allocation. PMID- 26887023 TI - Learning Instance Correlation Functions for Multilabel Classification. AB - Multilabel learning has a wide range of potential applications in reality. It attracts a great deal of attention during the past years and has been extensively studied in many fields including image annotation and text categorization. Although many efforts have been made for multilabel learning, there are two challenging issues remaining, i.e., how to exploit the correlations and how to tackle the high-dimensional problems of multilabel data. In this paper, an effective algorithm is developed for multilabel classification with utilizing those data that are relevant to the targets. The key is the construction of a coefficient-based mapping between training and test instances, where the mapping relationship exploits the correlations among the instances, rather than the explicit relationship between the variables and the class labels of data. Further, a constraint, l1-norm penalty, is performed on the mapping relationship to make the model sparse, weakening the impacts of noisy data. Our empirical study on eight public datasets shows that the proposed method is more effective in comparing with the state-of-the-art multilabel classifiers. PMID- 26887024 TI - Learning Nonparametric Relational Models by Conjugately Incorporating Node Information in a Network. AB - Relational model learning is useful for numerous practical applications. Many algorithms have been proposed in recent years to tackle this important yet challenging problem. Existing algorithms utilize only binary directional link data to recover hidden network structures. However, there exists far richer and more meaningful information in other parts of a network which one can (and should) exploit. The attributes associated with each node, for instance, contain crucial information to help practitioners understand the underlying relationships in a network. For this reason, in this paper, we propose two models and their solutions, namely the node-information involved mixed-membership model and the node-information involved latent-feature model, in an effort to systematically incorporate additional node information. To effectively achieve this aim, node information is used to generate individual sticks of a stickbreaking process. In this way, not only can we avoid the need to prespecify the number of communities beforehand, the algorithm also encourages that nodes exhibiting similar information have a higher chance of assigning the same community membership. Substantial efforts have been made toward achieving the appropriateness and efficiency of these models, including the use of conjugate priors. We evaluate our framework and its inference algorithms using real-world data sets, which show the generality and effectiveness of our models in capturing implicit network structures. PMID- 26887025 TI - Blind Domain Adaptation With Augmented Extreme Learning Machine Features. AB - In practical applications, the test data often have different distribution from the training data leading to suboptimal visual classification performance. Domain adaptation (DA) addresses this problem by designing classifiers that are robust to mismatched distributions. Existing DA algorithms use the unlabeled test data from target domain during training time in addition to the source domain data. However, target domain data may not always be available for training. We propose a blind DA algorithm that does not require target domain samples for training. For this purpose, we learn a global nonlinear extreme learning machine (ELM) model from the source domain data in an unsupervised fashion. The global ELM model is then used to initialize and learn class specific ELM models from the source domain data. During testing, the target domain features are augmented with the reconstructed features from the global ELM model. The resulting enriched features are then classified using the class specific ELM models based on minimum reconstruction error. Extensive experiments on 16 standard datasets show that despite blind learning, our method outperforms six existing state-of-the-art methods in cross domain visual recognition. PMID- 26887026 TI - An Inertial Projection Neural Network for Solving Variational Inequalities. AB - Recently, projection neural network (PNN) was proposed for solving monotone variational inequalities (VIs) and related convex optimization problems. In this paper, considering the inertial term into first order PNNs, an inertial PNN (IPNN) is also proposed for solving VIs. Under certain conditions, the IPNN is proved to be stable, and can be applied to solve a broader class of constrained optimization problems related to VIs. Compared with existing neural networks (NNs), the presence of the inertial term allows us to overcome some drawbacks of many NNs, which are constructed based on the steepest descent method, and this model is more convenient for exploring different Karush-Kuhn-Tucker optimal solution for nonconvex optimization problems. Finally, simulation results on three numerical examples show the effectiveness and performance of the proposed NN. PMID- 26887027 TI - Sequential Organ Failure Assessment Score at Presentation Predicts Survival in Patients Treated With Percutaneous Veno-Arterial Extracorporeal Membrane Oxygenation. AB - BACKGROUND AND PURPOSE: This study sought to investigate demographic, clinical, and procedural determinants of outcomes in patients treated with percutaneous veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) initiated in the cardiac catheterization laboratory with a portable system. METHODS: We performed a retrospective review of patients treated with percutaneous VA-ECMO during the study period at our institution. A logistic regression model was applied to investigate the association between sequential organ failure assessment (SOFA) score and survivor status. Fisher's exact test was used to examine the association between survivor status and cannula size (15 Fr vs >15 Fr). RESULTS: Percutaneous VA-ECMO was initiated in 25 patients. At 30 days, 10 patients were alive (40%). Fifteen patients had cardiac arrest (CA) prior to ECMO initiation, of which 5 were alive at 30 days (33%). Survivors had a lower baseline median SOFA score (9 vs 16; P=.02; odds ratio, 0.577). Use of a smaller cannula was associated with survival (P=.01). There was an association between the size of the arterial cannula and increased blood transfusions (P<.01). CONCLUSIONS: Lower presenting SOFA score and smaller cannula size were associated with increased survival in patients with cardiogenic shock (CS) or CA who underwent percutaneous VA-ECMO placed in the cardiac catheterization laboratory using a portable system. Calculation of the SOFA score at presentation may help physicians determine which patients may derive benefit from ECMO. Smaller cannula size, while decreasing the amount of flow, may result in decreased bleeding and increased survival. PMID- 26887028 TI - Left Radial Versus Femoral Access for Coronary Angiography in Post-Coronary Artery Bypass Graft Surgery Patients. AB - It has been recently demonstrated that coronary angiography of native coronary arteries via the radial artery results in reduced morbidity and mortality, when compared with a femoral approach. However, the efficacy and safety of the transradial approach in patients with coronary grafts is relatively unknown. We performed a retrospective audit of all patients with a history of previous coronary artery bypass graft (CABG) surgery who underwent diagnostic angiography at our institution from 2008-2012. The primary efficacy endpoint was procedure time (minutes), while the secondary efficacy measure was patient radiation exposure (MUGy/m2). There were 326 post-CABG patients studied during the defined period, with 254 via femoral approach and 72 via left radial artery. There was no significant difference between the two approaches in procedure time (37 minutes in radial group vs 35 minutes in femoral group; t-test, P=.43). There was also no difference in radiation exposure (7855 MUGy/m2 in femoral group vs 6825 MUGy/m2 in radial group; Satterthwaite t-test, P=.08). This study shows the validity of a left radial approach in patients who have undergone angiography post CABG. It suggests that transradial angiography can be safely performed in these patients, without significant increase in procedural time or radiation exposure. PMID- 26887029 TI - Impact of Surgical Consultation on Outcomes in Hemodynamically Supported High Risk Percutaneous Coronary Intervention: Insights From PROTECT II Randomized Study. AB - BACKGROUND: In observational studies of patients undergoing percutaneous coronary intervention (PCI), surgical ineligibility is associated with increased mortality. Whether the use of hemodynamic support during PCI can mitigate the adverse prognostic importance of surgical ineligibility is unknown. METHODS AND RESULTS: We sought to evaluate the association between request for surgical consultation (presumed surgical ineligibility) prior to PCI and clinical outcomes in 427 patients with multivessel coronary artery disease or unprotected left main disease and severely reduced left ventricular systolic function undergoing PCI assisted by hemodynamic support (intraaortic balloon pump or Impella) from the PROTECT II randomized trial. Patients in whom surgical consultation was requested prior to PCI (n = 201) were compared with those in whom surgical consultation was not requested (n = 226). The primary endpoint of this analysis was the composite of 90-day major adverse cardiac and cerebrovascular events (MACCE). Demographic and procedural variables were similar between patients receiving surgical consultation and patients not receiving surgical consultation, with the exception that the prevalence of prior coronary artery bypass graft surgery was significantly higher in patients not receiving surgical consultation (42.0% vs 25.4%; P<.001); these patients also had a higher proportion of lesions within a saphenous vein graft, and a greater prevalence of moderate/severe vessel calcification. MACCE rate at 90 days was similar in patients receiving surgical consultation compared with patients not receiving surgical consultation (23.4% vs 29.0%, respectively; P=.19). CONCLUSIONS: In this high-risk cohort of patients undergoing hemodynamically supported PCI, clinical outcome was not associated with an antecedent request for surgical consultation (presumed surgical ineligibility). Whether the use of hemodynamically supported PCI can lessen the risk conferred by surgical ineligibility requires further study. PMID- 26887030 TI - Changing exposures in a changing world: models for reducing the burden of disease. AB - Environmental exposures are changing dramatically in location, intensity, and frequency. Many developing countries are undergoing a transition in which they face the double burden of infectious diseases as well as chronic diseases. Noncommunicable diseases have emerged as the leading cause of death and disability in developing countries. Globally, pollution is insufficiently appreciated and inadequately quantified as a cause of disease. The health burden from both noninfectious diseases and infectious disease, especially parasites, is high among exposed people. Mothers and children are particularly vulnerable to pollution-related diseases in developing countries. Exposures to pollution can cause protracted noncommunicable diseases across their life span. A global initiative to promote human health sciences and technologies would enhance collaborations and communications amongst investigators and public environmental health officials. Existing models that facilitate the transfer of information and research results exist and can provide insight into building such an international network, allowing better prediction of disease risk and provide ways to reduce exposure to environmental contaminants. A global network would bring together scientists from multiple disciplines and countries to work toward a better understanding of the double burden of disease, especially in low and middle income countries, and promote ways to improve public health. PMID- 26887031 TI - Determination of antepartum and intrapartum risk factors associated with neonatal intensive care unit admission. AB - OBJECTIVE: To determine antepartum and intrapartum factors that are associated with admission to neonatal intensive care unit (NICU) among infants delivered between 36.0 and 42.0 weeks at our institution. METHODS: The retrospective cohort study included 73 consecutive NICU admissions and 375 consecutive non-NICU admissions. Data on demographic, antepartum, intrapartum and neonatal factors were collected. The primary endpoint defined was admission to NICU. Univariate analyses using the Student's t-test, Mann-Whitney U-test, chi2 Fisher's exact test was performed along with multivariate analysis of significant non-redundant variables. RESULTS: Those with a significantly higher risk of NICU admission underwent induction of labor with prostaglandin analogs (12.5% vs. 24.7%, P=0.007). Length of first stage >=720 min (33.5% vs. 51.9%, P=0.011), length of second stage of labor >=240 min (10.6% vs. 31.6%, P<0.001) and prolonged rupture of membranes >=120 min (54.0% vs. 80.0%, P=0.001) were all associated with an increased chance of NICU admission. Intrapartum factors predictive of NICU admission included administration of meperidine (11.7% vs. 27.4%, P<0.001), presence of preeclampsia (5.5% vs. 0.8%, P=0.015), use of intrapartum IV antihypertensives (1.1% vs. 13.7%, P<0.001), maternal fever (5.3% vs. 31.5%, P<0.001), fetal tachycardia (1.9% vs. 12.3%, P<0.001), and presence of meconium (30% vs. 8%, P<0.001). CONCLUSION: Identification of modifiable risk factors may reduce neonatal morbidity and mortality. Results from this study can be used to develop and validate a risk model based on combined antepartum and intrapartum risk factors. PMID- 26887032 TI - Waist-to-height ratio as a marker of low-grade inflammation in obese children and adolescents. AB - BACKGROUND: The epidemic of childhood obesity is associated with early atherosclerosis. Several reports have related this event to low-grade inflammation described in obesity. CRP and IL6 are markers that correlate with adiposity. The waist-to-height ratio (WtHR) is an anthropometric marker associated with insulin resistance and inflammation. The objective of this study was to assess the correlation between WtHR, metabolic complications and pro inflammatory factors in obese children and adolescents. METHODS: Weight, height, waist circumference, glycemia, insulin, CRP, TNF-alpha and IL-6 were measured in the baseline sample in 280 patients 6-19 years of age with overweight or obesity (OW/OB) and 112 normal-weight controls. Logistic regression was performed using WtHR as an independent variable. p>0.05 STATA11. RESULTS: Mean WtHR was 0.6+/ 0.06 in OW/OB and 0.43+/-0.02 in controls (p<0.01). WtHR was increased in 93% of the OW/OB vs. 2% of the controls. In the OW/OB inflammatory markers were significantly increased (p<0.01) compared to the controls (CRP 2.2 vs. 0.8; Il-6 2.9 vs. 2.1; and TNF-alpha 6.2 vs. 5.5). In the WtHR>0.5, insulin resistence and inflammatory markers were significantly increased (p<0.01) compared to the WtHR<0.5 (HOMA 3.4 vs. 1.4; CRP 2.3 vs. 0.6; Il-6 2.9 vs. 2.1; and TNF-alpha 6.4 vs. 5.55). In logistic regression, a significant independent association was found between WtHR with CRP (OR1.47), IL6 (OR1.60) and TNF-alpha (OR1.79). CONCLUSIONS: Obese children and adolescents have high inflammatory markers that may increase cardiovascular risk. WtHR is associated with low-grade inflammation and may be considered a relevant anthropometric marker in the clinical practice. PMID- 26887033 TI - Pituitary gigantism: a retrospective case series. AB - BACKGROUND: Pituitary gigantism (PG) is a rare pediatric disease with poorly defined long-term outcomes. Our aim is to describe the longitudinal clinical course in PG patients using a single-center, retrospective cohort study. METHODS: Patients younger than 19 years diagnosed with PG were identified. Thirteen cases were confirmed based on histopathology of a GH secreting adenoma or hyperplasia and a height >2 SD for age and gender. Laboratory studies, initial pathology, and imaging were abstracted. RESULTS: Average age at diagnosis was 13 years with an average initial tumor size of 7.4*3.8 mm. Initial transsphenoidal surgery was curative in 3/12 patients. Four of the nine patients who failed the initial surgery required a repeat procedure. Octreotide successfully normalized GH levels in 1/6 patients with disease refractory to surgery (1/6). Two out of five patients received pegvisomant after failing octreotide but only one patient responded to treatment. Five patients were ultimately treated with radiosurgery or radiation patients were followed for an average of 10 years. CONCLUSIONS: PG is difficult to treat. In most patients, the initial transsphenoidal surgery failed to normalize GH levels. If the initial surgery was unsuccessful, repeat surgery was unlikely to control GH secretion. Treatment with octreotide or pegvisomant was successful in less than half the patients failing surgery. Radiosurgery was curative, but is not an optimal treatment for pediatric patients. Despite the small sample, our study suggests that the treatment outcome of pediatric PG may be different than adults. PMID- 26887034 TI - Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty. AB - BACKGROUND: Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6 month formulation is approved for prostate cancer therapy. This is the first study in patients with CPP. METHODS: The efficacy and safety of the triptorelin 6 month formulation in CPP were investigated. The primary objective was to evaluate the efficacy in achieving luteinizing hormone (LH) suppression to pre-pubertal levels at month 6. This was an international, non-comparative phase III study over 48 weeks. Eighteen medical centers in the US, Chile and Mexico participated. Forty-four treatment naive patients (39 girls and five boys) aged at treatment start 2-8 years for girls and 2-9 years for boys with an advancement of bone age over chronological age >=1 year were to be included. Triptorelin was administered im twice at an interval of 24 weeks. LH, follicle stimulating hormone (FSH) (basal and stimulated), estradiol (girls), testosterone (boys), auxological parameters, clinical signs of puberty and safety were assessed. RESULTS: Forty one patients (93.2%) showed pre-pubertal LH levels (stimulated LH <=5 IU/L) at month 6 and maintained LH suppression through month 12. The percentage of patients with LH suppression exceeded 93% at each time point and reached 97.7% at month 12. No unexpected drug-related adverse events were reported. CONCLUSIONS: The triptorelin 6-month formulation was safe and effective in suppressing the pituitary-gonadal axis in children with CPP. The extended injection interval may improve compliance and increase comfort in the management of CPP. PMID- 26887035 TI - Assessment of paediatric pain: a critical review. AB - Pain is a complex experience, and its quantification involves many aspects including physiological, behavioural, and psychological factors. References related to the topic were selected and analysed, along with a PubMed search of the recent and earlier reports. Assessment of pain in infants and children has always been a dilemma for the clinicians. Unlike in adults, it is difficult to assess and effectively treat pain in paediatric age groups, and it often remains untreated or undertreated. Misperceptions are attributed not only to the difficulties in isolating the specific signs of pain but also in recognising and inferring the meaning of the cues available in the complex of individual differences in the reaction pattern of children to pain. In children, several parameters such as age, cognitive level, type of pain, etc. are required to be considered for the selection of appropriate pain assessment tools. Although considerable progress has been made, there is a critical need for a more accurate measurement tool for both research and clinical purposes. This review has critically analysed the various techniques available to assess pain in children with emphasis on current research and present-day status of paediatric pain assessment. PMID- 26887036 TI - A collaboration investigating endocannabinoid signalling in brain and bone. AB - Investigations into the cellular and molecular mechanisms underlying the psychoactive effects of cannabis preparations have led to the discovery of the endocannabinoid system. Interest in the central nervous system effects was initially the main focus of the research, but it soon became evident that the endocannabinoid system affects virtually every organ. The research field has therefore experienced a tremendous growth over the last decade and is now truly interdisciplinary. This short review provides a personal account of an interdisciplinary collaboration between Itai Bab from the Hebrew University of Jerusalem and the author. It describes the discovery of the endocannabinoid system in bone and the analysis of its functions. I am summarising the role of CB1 signalling as a modulator of sympathetic inhibition of bone formation. Thus, activation of CB1 receptors on sympathetic nerve terminals in bone, presumably from endocannabinoids released from apposing osteoblasts, reduces the inhibition of bone formation of sympathetic norepinephrine. CB2 receptors on osteoblasts and osteoclasts also modulate the proliferation and functions of these cells. Thus, activation of CB2 stimulates bone formation and represses bone resorption, whereas the genetic disruption of CB2 results in an osteoporosis-like phenotype. This signalling mechanism is clinically relevant, as shown by the association of polymorphisms in the CB2 receptor gene, CNR2, with bone density and osteoporosis. Finally, the review provides a summary of the recently discovered role of endocannabinoid signalling in one elongation. This review will also discuss the benefits of interdisciplinary and international collaborations. PMID- 26887037 TI - Human dipeptidyl peptidase III regulates G-protein coupled receptor-dependent Ca2+ concentration in human embryonic kidney 293T cells. AB - The precise biological function of human dipeptidyl peptidase III (hDPP III) is poorly understood. Using luciferase reporter constructs responsive to change in Ca2+ and/or cAMP and Fura 2-AM fluorometric assay, we show a significant decrease in intracellular Ca2+ following hDPP III overexpression and angiotensin II stimulation in angiotensin II type 1 receptor (G-protein coupled receptor, GPCR) expressing HEK293T cells. Silencing the expression of hDPP III by siRNA reversed the effect of hDPP III overexpression with a concomitant increase in Ca2+. These results, for the first time, show involvement of hDPP III in GPCR dependent Ca2+ regulation in HEK293T cells. PMID- 26887038 TI - Derivation of level-specific reference change values (RCV) from a health screening database and optimization of their thresholds based on clinical utility. AB - BACKGROUND: Reference change values (RCV) are used for judging the significance of changes between any two measurements. Based on the within-individual CV (CVI), RCV is conventionally computed as the 95% confidence limit (CL) of the changes: RCV=1.96*2CVI. $RCV = 1.96 ?times ?sqrt 2 C{V_I}.$ However, the appropriateness of assuming a constant CVI and using the 95% CL for RCV remains controversial. METHODS: The level-specific CVI and RCV were estimated for 20 screening tests using a database composed of results from 13,545 health-screening attendees over a 17-year period, after preliminary exclusion of individuals taking medications or having unusual changes in body mass index (BMI). A rational CL for RCV was explored in reference to a clinical score for the metabolic syndrome, sMS, which was derived based on a logistic regression model consisting of tests related to metabolic syndrome. The effect of adjusting CL for the RCV on diagnostic efficacies of detecting between-year change in sMS was evaluated. RESULTS: Test level dependency of CVI was apparent for some screening tests which have distributions with prominent skewing. The use of level-specific RCV was thus essential for them. The sensitivity for detecting a critical change in sMS based on the RCV set at 95%CL was extremely low in the majority of tests. However, by lowering CL stepwise from 95 to 75%, the sensitivity improved greatly without much change in specificity and positive predictive value. Loss-and-gain analysis showed that CL for RCV set around 80% gave the lowest loss, assuming a policy of reducing false negative judgment. CONCLUSIONS: Level specific CVI and RCV were necessary in tests with skewed distributions. RCV using 80%-90% CL is suitable in health screening for diseases that require early intervention for changes. PMID- 26887039 TI - A technical and clinical evaluation of a new assay for inhibin A and its use in second trimester Down syndrome screening. AB - BACKGROUND: The objective of the study was to compare a new AutoDELFIA(r) Inhibin A kit (B064-102) with the Access Inhibin A kit (A36097) using clinical specimens and to evaluate the AutoDELFIA(r) Inhibin A assay performance in screening for Down syndrome in the second trimester of pregnancy. METHODS: Using clinical samples, we performed a method comparison between new and existing inhibin A kits and assessed AutoDELFIA(r) Inhibin A kit precision performance. Normal median values for the second trimester of pregnancy were also determined. Finally, we evaluated the screening performance of the AutoDELFIA(r) Inhibin A kit together with other second trimester biomarkers for the detection of Down syndrome. RESULTS: The two methods showed a high degree of correlation (r=0.99, Pearson and Spearman correlation), and the average relative level difference between the methods at a concentration range of 41.7-1925 pg/mL was 19.6% [95% confidence interval (CI) from 17.6% to 21.5%]. The acceptable precision of the AutoDELFIA(r) Inhibin A kit was demonstrated: the within-lot CV% varied from 1.9% to 3.9%. The screening performance results show that AutoDELFIA(r) Inhibin A when added to a combination of other second trimester serum markers [human alpha foetoprotein (hAFP), free beta subunit of human chorionic gonadotropin (free hCGbeta) and unconjugated estriol (uE3) or hAFP and free hCGbeta] improves the detection rate of screening in both combinations. CONCLUSIONS: The performance of the AutoDELFIA(r) Inhibin A assay is highly acceptable for routine laboratory use for screening Down syndrome in the second trimester of pregnancy. PMID- 26887040 TI - Fibroblast growth factor 21 (FGF-21) in obese children: no relationship to growth, IGF-1, and IGFBP-3. AB - BACKGROUND: Fibroblast growth factor 21 (FGF-21) is a hepatic protein that plays a critical role in liver, adipose tissue, and bone metabolism. Animal models reported an increase of FGF-21 and associated growth disturbances in undernutrition. Therefore, we studied the impact of weight loss in obese children on growth, FGF-21, and insulin-like factor 1 (IGF-1) concentrations. METHODS: We analyzed height, serum concentrations of FGF-21, IGF-1, IGFBP-3, leptin, and insulin at baseline and 1 year later in 30 obese children with substantial weight loss (reduction >0.5 BMI-SDS) and in 30 obese children of similar age, gender, and pubertal stage with stable BMI-SDS. All children participated in a 1-year lifestyle intervention. Height and IGF-1 was transformed to standard deviation score (SDS). Multiple linear regression analyses adjusted for age, gender, and pubertal stage were performed. RESULTS: At baseline, height-SDS was significantly related to IGF-1-SDS (beta-coefficient 0.68 95% confidence interval (95% CI)+/ 0.49; p=0.008) and leptin (beta-coefficient 0.042 95% CI+/-0.030; p=0.008), but not to FGF-21 or insulin. FGF-21 was not significantly associated with IGF-1 or IGFBP-3. In longitudinal analysis, changes of FGF-21 were not significantly related to changes of height, IGF-1-SDS or IGFBP-3. However, in the subgroup of 30 children with substantial BMI-SDS reduction, FGF-21, leptin, insulin, and HOMA decreased significantly. CONCLUSION: As there was no significant association between FGF-21 and growth or IGF-1 both in cross-sectional and longitudinal analyses, these findings do not support the hypothesis that FGF-21 is involved in growth of obese children. Further studies are necessary to understand the multiple alterations in the growth hormone (GH) axis in obese children. PMID- 26887041 TI - HMM-DM: identifying differentially methylated regions using a hidden Markov model. AB - DNA methylation is an epigenetic modification involved in organism development and cellular differentiation. Identifying differential methylations can help to study genomic regions associated with diseases. Differential methylation studies on single-CG resolution have become possible with the bisulfite sequencing (BS) technology. However, there is still a lack of efficient statistical methods for identifying differentially methylated (DM) regions in BS data. We have developed a new approach named HMM-DM to detect DM regions between two biological conditions using BS data. This new approach first uses a hidden Markov model (HMM) to identify DM CG sites accounting for spatial correlation across CG sites and variation across samples, and then summarizes identified sites into regions. We demonstrate through a simulation study that our approach has a superior performance compared to BSmooth. We also illustrate the application of HMM-DM using a real breast cancer dataset. PMID- 26887042 TI - MLN-8237: A dual inhibitor of aurora A and B in soft tissue sarcomas. AB - Aurora kinases have become an attractive target in cancer therapy due to their deregulated expression in human tumors. Liposarcoma, a type of soft tissue sarcoma in adults, account for approximately 20% of all adult soft tissue sarcomas. There are no effective chemotherapies for majority of these tumors. Efforts made to define the molecular basis of liposarcomas lead to the finding that besides the amplifications of CDK4 and MDM2, Aurora Kinase A, also was shown to be overexpressed. Based on these as well as mathematic modeling, we have carried out a successful preclinical study using CDK4 and IGF1R inhibitors in liposarcoma. MLN8237 has been shown to be a potent and selective inhibitor of Aurora A. MLN-8237, as per our results, induces a differential inhibition of Aurora A and B in a dose dependent manner. At a low nanomolar dose, cellular effects such as induction of phospho-Histone H3 (Ser10) mimicked as that of the inhibition of Aurora kinase A followed by apoptosis. However, micromolar dose of MLN-8237 induced polyploidy, a hallmark effect of Aurora B inhibition. The dose dependent selectivity of inhibition was further confirmed by using siRNA specific inhibition of Aurora A and B. This was further tested by time lapse microscopy of GFP-H2B labelled cells treated with MLN-8237. LS141 xenograft model at a dose of 30 mg/kg also showed efficient growth suppression by selective inhibition of Aurora Kinase A. Based on our data, a dose that can target only Aurora A will be more beneficial in tumor suppression. PMID- 26887043 TI - Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling. AB - Chemo/radio-therapy resistance to the deadly pancreatic cancer is mainly due to the failure to kill pancreatic cancer stem cells (CSCs). Signal transducer and activator of transcription 3 (STAT3) is activated in pancreatic CSCs and, therefore, may be a valid target for overcoming therapeutic resistance. Here we investigated the potential of STAT3 inhibition in sensitizing pancreatic cancer to chemo/radio-therapy. We found that the levels of nuclear pSTAT3 in pancreatic cancer correlated with advanced tumor grade and poor patient outcome. Liposomal delivery of a STAT3 inhibitor FLLL32 (Lip-FLLL32) inhibited STAT3 phosphorylation and STAT3 target genes in pancreatic cancer cells and tumors. Consequently, Lip FLLL32 suppressed pancreatic cancer cell growth, and exhibited synergetic effects with gemcitabine and radiation treatment in vitro and in vivo. Furthermore, Lip FLLL32 reduced ALDH1-positive CSC population and modulated several potential stem cell markers. These results demonstrate that Lip-FLLL32 suppresses pancreatic tumor growth and sensitizes pancreatic cancer cells to radiotherapy through inhibition of CSCs in a STAT3-dependent manner. By targeting pancreatic CSCs, Lip FLLL32 provides a novel strategy for pancreatic cancer therapy via overcoming radioresistance. PMID- 26887044 TI - Targeting the p53-MDM2 interaction by the small-molecule MDM2 antagonist Nutlin 3a: a new challenged target therapy in adult Philadelphia positive acute lymphoblastic leukemia patients. AB - MDM2 is an important negative regulator of p53 tumor suppressor. In this study, we sought to investigate the preclinical activity of the MDM2 antagonist, Nutlin 3a, in Philadelphia positive (Ph+) and negative (Ph-) leukemic cell line models, and primary B-acute lymphoblastic leukemia (ALL) patient samples. We demonstrated that Nutlin-3a treatment reduced viability and induced p53-mediated apoptosis in ALL cells with wild-type p53 protein, in a time and dose-dependent manner, resulting in the increased expression of pro-apoptotic proteins and key regulators of cell cycle arrest. The dose-dependent reduction in cell viability was confirmed in primary blast cells from B-ALL patients, including Ph+ ALL resistant patients carrying the T315I BCR-ABL1 mutation. Our findings provide a strong rational for further clinical investigation of Nutlin-3a in Ph+ and Ph- ALL. PMID- 26887045 TI - Targeting DNA repair by coDbait enhances melanoma targeted radionuclide therapy. AB - Radiolabelled melanin ligands offer an interesting strategy for the treatment of disseminated pigmented melanoma. One of these molecules, ICF01012 labelled with iodine 131, induced a significant slowing of melanoma growth. Here, we have explored the combination of [131I]ICF01012 with coDbait, a DNA repair inhibitor, to overcome melanoma radioresistance and increase targeted radionuclide therapy (TRT) efficacy. In human SK-Mel 3 melanoma xenograft, the addition of coDbait had a synergistic effect on tumor growth and median survival. The anti-tumor effect was additive in murine syngeneic B16Bl6 model whereas coDbait combination with [131I]ICF01012 did not increase TRT side effects in secondary pigmented tissues (e.g. hair follicles, eyes). Our results confirm that DNA lesions induced by TRT were not enhanced with coDbait association but, the presence of micronuclei and cell cycle blockade in tumor shows that coDbait acts by interrupting or delaying DNA repair. In this study, we demonstrate for the first time, the usefulness of DNA repair traps in the context of targeted radionuclide therapy. PMID- 26887046 TI - Rapid generation of novel models of RAG1 deficiency by CRISPR/Cas9-induced mutagenesis in murine zygotes. AB - Mutations in the Recombination Activating Gene 1 (RAG1) can cause a wide variety of clinical and immunological phenotypes in humans, ranging from absence of T and B lymphocytes to occurrence of autoimmune manifestations associated with expansion of oligoclonal T cells and production of autoantibodies. Although the mechanisms underlying this phenotypic heterogeneity remain poorly understood, some genotype-phenotype correlations can be made. Currently, mouse models of Rag deficiency are restricted to RAG1-/- mice and to knock-in models carrying severe missense mutations. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 system is a novel and powerful gene-editing strategy that permits targeted introduction of DNA double strand breaks with high efficiency through simultaneous delivery of the Cas9 endonuclease and a guide RNA (gRNA). Here, we report on CRISPR-based, single-step generation and characterization of mutant mouse models in which gene editing was attempted around residue 838 of RAG1, a region whose functional role had not been studied previously. PMID- 26887047 TI - Retrospective study testing next generation sequencing of selected cancer associated genes in resected prostate cancer. AB - PURPOSE: Prostate cancer (PCa) has a highly heterogeneous outcome. Beyond Gleason Score, Prostate Serum Antigen and tumor stage, nowadays there are no biological prognostic factors to discriminate between indolent and aggressive tumors.The most common known genomic alterations are the TMPRSS-ETS translocation and mutations in the PI3K, MAPK pathways and in p53, RB and c-MYC genes.The aim of this retrospective study was to identify by next generation sequencing the most frequent genetic variations (GVs) in localized and locally advanced PCa underwent prostatectomy and to investigate their correlation with clinical-pathological variables and disease progression. RESULTS: Identified non-synonymous GVs included TP53 p.P72R (78% of tumors), two CSFR1 SNPs, rs2066934 and rs2066933 (70%), KDR p.Q472H (67%), KIT p.M541L (28%), PIK3CA p.I391M (19%), MET p.V378I (10%) and FGFR3 p.F384L/p.F386L (8%). TP53 p.P72R, MET p.V378I and CSFR1 SNPs were significantly associated with the HI risk group, TP53 and MET variations with T>=T2c. FGFR3 p.F384L/p.F386L was correlated with T<=T2b. MET p.V378I mutation, detected in 20% of HI risk patients, was associated with early biochemical recurrence. EXPERIMENTAL DESIGN: Nucleic acids were obtained from tissue samples of 30 high (HI) and 30 low-intermediate (LM) risk patients, according to D'Amico criteria. Genomic DNA was explored with the Ion_AmpliSeq_Cancer_Hotspot_Panel_v.2 including 50 cancer-associated genes. GVs with allelic frequency (AF) >=10%, affecting protein function or previously associated with cancer, were correlated with clinical-pathological variables. CONCLUSION: Our results confirm a complex mutational profile in PCa, supporting the involvement of TP53, MET, FGFR3, CSF1R GVs in tumor progression and aggressiveness. PMID- 26887048 TI - Prognostic relevance of HER2/neu in acute lymphoblastic leukemia and induction of NK cell reactivity against primary ALL blasts by trastuzumab. AB - The epidermal growth factor receptor HER2/neu is expressed on various cancers and represents a negative prognostic marker, but is also a target for the therapeutic monoclonal antibody Trastuzumab. In about 30% of cases, HER2/neu is expressed on acute lymphoblastic leukemia (ALL) cells and was proposed to be associated with a deleterious prognosis. Here we evaluated clinical data from 65 ALL patients (HER2/neu+, n = 17; HER2/neu-, n = 48) with a median follow-up of 19.4 months (range 0.6-176.5 months) and observed no association of HER2/neu expression with response to chemotherapy, disease free or overall survival. In vitro, treatment of primary ALL cells (CD20+HER2/neu+, CD20+HER2/neu- and CD20-HER2/neu-) with Rituximab and Trastuzumab led to activation of NK cells in strict dependence of the expression of the respective antigen. NK reactivity was more pronounced with Rituximab as compared to Trastuzumab, and combined application could lead to additive effects in cases where both antigens were expressed. Besides providing evidence that HER2/neu expression is no risk factor in ALL patients, our data demonstrates that HER2/neu can be a promising target for Trastuzumab therapy in the subset of ALL patients with the potential to improve disease outcome. PMID- 26887049 TI - Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport. AB - Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARalpha, PPARgamma, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARalpha, and PPARgamma represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARalpha, or PPARgamma. Most strikingly, pirinixic acid derivatives interfered with drug transport by the ATP-binding cassette (ABC) transporter ABCB1 in a drug specific fashion. LP117, the compound that exerted the strongest effect on ABCB1, interfered in the investigated concentrations of up to 2MUM with the ABCB1 mediated transport of vincristine, vinorelbine, actinomycin D, paclitaxel, and calcein-AM but not of doxorubicin, rhodamine 123, or JC-1. In silico docking studies identified differences in the interaction profiles of the investigated ABCB1 substrates with the known ABCB1 binding sites that may explain the substrate-specific effects of LP117. Thus, pirinixic acid derivatives may offer potential as drug-specific modulators of ABCB1-mediated drug transport. PMID- 26887050 TI - MicroRNA-138 promotes acquired alkylator resistance in glioblastoma by targeting the Bcl-2-interacting mediator BIM. AB - Glioblastoma is the most aggressive brain tumor in adults with a median survival below 12 months in population-based studies. The main reason for tumor recurrence and progression is constitutive or acquired resistance to the standard of care of surgical resection followed by radiotherapy with concomitant and adjuvant temozolomide (TMZ/RT->TMZ). Here, we investigated the role of microRNA (miRNA) alterations as mediators of alkylator resistance in glioblastoma cells. Using microarray-based miRNA expression profiling of parental and TMZ-resistant cultures of three human glioma cell lines, we identified a set of differentially expressed miRNA candidates. From these, we selected miR-138 for further functional analyses as this miRNA was not only upregulated in TMZ-resistant versus parental cells, but also showed increased expression in vivo in recurrent glioblastoma tissue samples after TMZ/RT->TMZ treatment. Transient transfection of miR-138 mimics in glioma cells with low basal miR-138 expression increased glioma cell proliferation. Moreover, miR-138 overexpression increased TMZ resistance in long-term glioblastoma cell lines and glioma initiating cell cultures. The apoptosis regulator BIM was identified as a direct target of miR 138, and its silencing mediated the induced TMZ resistance phenotype. Altered sensitivity to apoptosis played only a minor role in this resistance mechanism. Instead, we identified the induction of autophagy to be regulated downstream of the miR-138/BIM axis and to promote cell survival following TMZ exposure. Our data thus define miR-138 as a glioblastoma cell survival-promoting miRNA associated with resistance to TMZ therapy in vitro and with tumor progression in vivo. PMID- 26887051 TI - Multi-kinase inhibitors can associate with heat shock proteins through their NH2 termini by which they suppress chaperone function. AB - We performed proteomic studies using the GRP78 chaperone-inhibitor drug AR-12 (OSU-03012) as bait. Multiple additional chaperone and chaperone-associated proteins were shown to interact with AR-12, including: GRP75, HSP75, BAG2; HSP27; ULK-1; and thioredoxin. AR-12 down-regulated in situ immuno-fluorescence detection of ATP binding chaperones using antibodies directed against the NH2 termini of the proteins but only weakly reduced detection using antibodies directed against the central and COOH portions of the proteins. Traditional SDS PAGE and western blotting assessment methods did not exhibit any alterations in chaperone detection. AR-12 altered the sub-cellular distribution of chaperone proteins, abolishing their punctate speckled patterning concomitant with changes in protein co-localization. AR-12 inhibited chaperone ATPase activity, which was enhanced by sildenafil; inhibited chaperone - chaperone and chaperone - client interactions; and docked in silico with the ATPase domains of HSP90 and of HSP70. AR-12 combined with sildenafil in a GRP78 plus HSP27 -dependent fashion to profoundly activate an eIF2alpha/ATF4/CHOP/Beclin1 pathway in parallel with inactivating mTOR and increasing ATG13 phosphorylation, collectively resulting in formation of punctate toxic autophagosomes. Over-expression of [GRP78 and HSP27] prevented: AR-12 -induced activation of ER stress signaling and maintained mTOR activity; AR-12 -mediated down-regulation of thioredoxin, MCL-1 and c-FLIP-s; and preserved tumor cell viability. Thus the inhibition of chaperone protein functions by AR-12 and by multi-kinase inhibitors very likely explains why these agents have anti-tumor effects in multiple genetically diverse tumor cell types. PMID- 26887052 TI - XPG rs2296147 T>C polymorphism predicted clinical outcome in colorectal cancer. AB - Xeroderma pigmentosum group G (XPG), one of key components of nucleotide excision repair pathway (NER), is involved in excision repair of UV-induced DNA damage. Single nucleotide polymorphisms (SNPs) in the XPG gene have been reported to associate with the clinical outcome of various cancer patients. We aimed to assess the impact of four potentially functional SNPs (rs2094258 C>T, rs2296147 T>C, rs751402 G>A, and rs873601 G>A) in the XPG gene on prognosis in colorectal cancer (CRC) patients. A total of 1901 patients diagnosed with pathologically confirmed CRC were genotyped for four XPG polymorphisms. Cox proportional hazards model analysis controlled for several confounding factors was conducted to compute hazard ratios (HRs) and 95% confidence intervals (CIs). Of the four included SNPs, only rs2296147 was shown to significantly affect progression-free survival (PFS) in CRC. Patients carrying rs2296147 CT/TT genotype had a significantly shorter median 10 years PFS than those carrying CC genotype (88.5 months vs. 118.1 months), and an increased progression risk were observed with rs2296147 (HR = 1.324, 95% CI = 1.046-1.667). Moreover, none of the four SNPs were associated with overall survival. In conclusion, our study showed that XPG rs2296147 CT/TT variants conferred significant survival disadvantage in CRC patients in term of PFS. XPG rs2296147 polymorphism could be predictive of unfavorable prognosis of CRC patients. PMID- 26887053 TI - NFE2L2 variations reduce antioxidant response in patients with Parkinson disease. AB - Oxidative stress has been recognized as a risk factor of Parkinson's disease (PD) development. We hypothesized that decreased function of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-antioxidant response element (ARE) pathway might predispose to Parkinsonism. A case-control study was performed between NFE2L2 Single Nucleotide Polymorphism (SNP) and PD in a cohort of 765 unrelated patients with diagnosis of PD and 489 matched normal individuals. We found that c.351T>A, D117E (P = 0.003, OR = 2.8) and c.351T>A, D117E (P = 0.012, OR = 1.9) were significantly associated with PD. The risk allele of both polymorphisms showed a high frequency in our PD sample (c.351A: 19.7% and c.423T: 7.8%). The association between both c.351T>A and c.423G>T and PD was further confirmed in an independent case-control cohort consisting of 210 individuals with PD and 148 normal controls. We further found that over expression of D117E and Q141H variants of NFE2L2 reduced target genes expression of Glutathione S-transferase Pi 1 (GSTP1), Glutathione S-transferase Mu 1 (GSTM1), and Heme oxygenase 1 (HO-1) genes. NFE2L2 D117E and Q141H impaired activation of ARE-driven transcriptional activity. Our findings indicate that NFE2L2 may play an important role in the pathogenesis of PD in Chinese populations. PMID- 26887054 TI - Identification of novel long non-coding RNAs deregulated in hepatocellular carcinoma using RNA-sequencing. AB - Functional characterization of long non-coding RNAs (lncRNAs) and their pathological relevance is still a challenging task. Abnormal expression of a few long non-coding RNAs have been found associated with hepatocellular carcinoma, with potential implications to both improve our understanding of molecular mechanism of liver carcinogenesis and to discover biomarkers for early diagnosis or therapy. However, the understanding of the global role of lncRNAs during HCC development is still in its infancy. In this study, we produced RNA-Seq data from 23 liver tissues (controls, cirrhotic and HCCs) and applied statistical and gene network analysis approaches to identify and characterize expressed lncRNAs. We detected 5,525 lncRNAs across different tissue types and identified 57 differentially expressed lncRNAs in HCC compared with adjacent non-tumour tissues using stringent criteria (FDR<0.05, Fold Change>2). Using weighted gene co expression network analysis (WGCNA), we found that differentially expressed lncRNAs are co-expressed with genes involved in cell cycle regulation, TGF-beta signalling and liver metabolism. Furthermore, we found that more than 20% of differentially expressed lncRNAs are associated to actively transcribed enhancers and that the co-expression patterns with their closest genes change dramatically during HCC development. Our study provides the most comprehensive compendium of lncRNAs expressed in HCC, as well as in control or cirrhotic livers. Our results identified both known oncogenic lncRNAs (such as H19 and CRNDE) and novel lncRNAs involved in cell cycle deregulation and liver metabolism deficits occurring during HCC development. PMID- 26887057 TI - Professor Doctor Crisan Mircioiu. PMID- 26887055 TI - Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme. AB - A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient's survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient's survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation. PMID- 26887056 TI - Long non-coding RNA MALAT1 increases AKAP-9 expression by promoting SRPK1 catalyzed SRSF1 phosphorylation in colorectal cancer cells. AB - Our earlier findings indicate that the long non-coding RNA MALAT1 promotes colorectal cancer (CRC) cell proliferation, invasion and metastasis in vitro and in vivo by increasing expression of AKAP-9. In the present study, we investigated the molecular mechanism by which MALAT1 enhances AKAP9 expression in CRC SW480 cells. We found that MALAT1 interacts with both SRPK1 and SRSF1. MALAT1 increases AKAP-9 expression by promoting SRPK1-catalyzed SRSF1 phosphorylation. Following MALAT1 knockdown, overexpression of SRPK1 was sufficient to restore SRSF1 phosphorylation and AKAP-9 expression to a level that promoted cell proliferation, invasion and migration in vitro. Conversely, SRPK1 knockdown after overexpression of MALAT1 in SW480 cells diminished SRSF1 phosphorylation and AKAP 9 expression and suppressed cell proliferation, invasion and migration in vitro. These findings suggest MALAT1 increases AKAP-9 expression by promoting SRPK1 catalyzed SRSF1 phosphorylation in CRC cells. These results reveal a novel molecular mechanism by which MALAT1 regulates AKAP-9 expression in CRC cells. PMID- 26887059 TI - A UNITED CLASSIFICATION IN CARCINOMA OF THE ESOPHAGUS AND THE CARDIA BASED ON THE LYMPH METASTASIS. AB - The problem of the surgical treatment of cancer of the esophagus-gastric transition is up to date until today and has caused disagreements between the surgeons. This is one of the most aggressive visceral tumors. Metastasis is very specific due to the specificity of lymph edema. We operated 213 patients for four years period, 162 of them male and 51 - female. Cancer cardia and lower third of the esophagus are seen in 163 of them. All carcinomas of the gastroesophageal transition are diagnosed as adenocarcinomas, which means there is an increase of this localization of the tumor. This distribution of cardiac carcinoma Sieber is almost equal in our series of patients. We operated 137 patients for three years period. Sieber 1 - 47 patients, Sieber 2 - 37 patients, Sieber 3 - 53 patients. The persentage raio is as follows: Sieber 1 - 34%, Sieber 2 - 27%, Sieber 3-39%. PMID- 26887058 TI - MULTIVISCERAL RESECTIONS FOR GASTRIC CANCER. AB - BACKGROUND: Multivisceral resection for locally advanced gastric cancer is necessary to achieve R0-margins. This surgical option is accompanied by short- and long-term outcomes that still remain questionable. AIM: Our aim was to evaluate the efficacy of "en bloc"-resections as an "aggressive" surgical approach with regard to postoperative morbidity, mortality and survival. MATERIAL AND METHODS: Postoperative morbidity, mortality and survival rates of 60 patients with locally advanced gastric carcinoma, who underwent total or subtotal gastrectomy with multivisceral resection between 2004-2014, were retrospectively analysed. RESULTS: The most common adjacent organs resected were spleen (n = 46) 76.7%, pancreas (n = 24) - 40%, colon (n = 11) - 18.3%, liver (n = 9) - 15% and duodenum (n = 4) - 6.7%. Resection of more than one organ was performed in 70% of cases, R0-resection was achieved in 75%, histopathologic examination confirmed involvement of adjacent organs (pT4) in 42 patients (70%). Surgical mortality and morbidity rates were 6.7% and 28.3% respectively. The overall 5-year survival rate was 24.1% (R0 vs R1 resections - 32.6 vs 0%, p < 0.05). There is a 10-year survival rate of 5.2% registered. CONCLUSION: R0-multivisceral resection is the key therapeutic option for advanced gastric cancer. It appears to be feasible in selected patients on providing adequate selection and surgical expertise and can be achieved with relatively low mortality and morbidity, offering good overall and 5-year survival rates. PMID- 26887060 TI - SINGLE-ACCESS TRANSUMBILICAL LAPAROSCOPIC APPENDECTOMY USING CURVED REUSABLE INSTRUMENTS: AN INITIAL REPORT OF THREE CASES. AB - INTRODUCTION: The continuous evolution of laparoscopic surgery and the ambition of better cosmetic results raise the need for less invasive procedures. The umbilicus represents a natural scar and constitutes a well-healing site of access to the peritoneal cavity. Single-access Transumbilical Laparoscopy (SATL) is gaining popularity and can be an alternative surgical treatment for acute appendicitis. We report three cases of SATL appendectomy using curved reusable instruments. PATIENTS AND METHODS: Three female patients, wanting minimal scarring (mean age - 30 years) were admitted to our hospital in April 2015 with acute abdominal pain in the right iliac area. A SATL appendectomy was performed using a standard 11-mm reusable trocar for a 10-mm, 30 degrees- angled, rigid scope and curved reusable instruments according to DAPRI (Karl Storz-Endoskope, Tuttlingen, Germany) placed transumbilically. RESULTS: Neither a conversion to open surgery nor an insertion of extraumbilical trocars was necessary. The mean operative time was 101.6 +/- 24.66 minutes and the mean blood loss 6.66 +/- 11.54 mL. The mean scar length was 16.66 +/- 0.57 mm. No intraoperative complications were registered and the use of minimal pain killers allowed the discharge after 2 or maximum 4 days. After three months of follow-up no late complications occurred and the umbilical scar was not visible. CONCLUSION: In young and scarless demanding females with acute appendicitis SATL appendectomy can be performed safely and offers the possibility of surgical treatment without a visible scar. PMID- 26887062 TI - TRENDS AND ALTERNATIVES IN TREATMENT OF MALIGNANT TUMORS OF EXTRAHEPATIC BILE DUCTS. AB - Neoplasms of extrahepatic bile ducts are rare and represent about 2% of all malignant diseases. Their clinical manifestation is delayed, when they are in advanced stage and the opportunities for radical treatment are limited. The resectability rate of the tumors of the middle and distal part of the bile ducts is higher than the percentage of the neoplasms with perihilar localization. Improved methods for preoperative diagnostic and staging as well as the individualized therapeutic approach, including biliary drainage, use of contemporary surgical techniques and methods, selective embolization of portal vein, partial hepatectomy, resection of caudal lobe, lead to increased rate of radical operations and improved long-term results. PMID- 26887061 TI - GIANT MORGAGNI HERNIA IN A FEMALE WITH MALROTATION SYNDROME AND THORACIC TRANSPOSITION OF SMALL BOWEL, COECUM, ASCENDING AND TRANSVERSE COLON. AB - The sterno-costal hernia of Morgagni is a congenital vice in which is represented unfinished fusion of the transverse septum and the muscular diaphragmal wall. The malrotation syndrome is an embryonic vice as well, with various degree of incomplete and even reverse rotation of the gut, because of disturbed or unfinished development of the midgut. The described case presents a 37 years old female without anamnesis of any previous complains, who was pointed to the clinic after a X-ray photograph because of breathless and asteno-adynamic syndrome. After a precise CT investigation performance was found the presence of the above described anomalities, as well as ectopy of the right kidney and the right liver part. An operative treatment was performed with correction of the hernia and the bowel malrotation. The patient was followed up to the 12th month post operatively. After a review of the literature in the discussion we inspect the diagnostics and the definition of the right surgical tactics and operative approach in this case with combined malformative pathology. PMID- 26887063 TI - It Isn't Just Happening to Medicine: Thoughts on My Year as MedChi President. PMID- 26887064 TI - Beating to Windward. Making Progress in Difficult Times. PMID- 26887065 TI - MedChi Sets Priorities for 2016. PMID- 26887067 TI - Introduction. PMID- 26887066 TI - I See Your Facebook and Raise You One Google! PMID- 26887068 TI - How to Manage Your Online Reputation. PMID- 26887069 TI - Who Are Healthcare Dropouts? A ZocDoc Study. PMID- 26887070 TI - Professional Social Networks Helping Solve Physician Communication Challenges. PMID- 26887071 TI - Text Messaging and Physician Communication: Tweeting Others as We Would Want to Be Tweeted. PMID- 26887072 TI - Diminishing the Risk of Physician-to-Physician Mobile Communication. PMID- 26887073 TI - Helping Future Patients Find Your Practice on the Internet: It's All About SEO. PMID- 26887075 TI - "A Servant to His Brethren". Osler's Impact on the University of Maryland School of Medicine and on MedChi. PMID- 26887074 TI - Legal and Ethical Concerns of Digital Media and Technology in Healthcare. PMID- 26887076 TI - Late Night Thoughts. PMID- 26887077 TI - Elemental Etymology. PMID- 26887078 TI - '360 Strategy' Tackles Heroin, Rx Drug Abuse. PMID- 26887079 TI - Informed Workers Are Safer Workers: Science Is the Key to FR Technology. PMID- 26887080 TI - If the Shoe Fits.... PMID- 26887081 TI - Footwear That Goes the Extra Mile. PMID- 26887083 TI - Key Ingredients: What Makes a Safety Strategy Effective. PMID- 26887082 TI - Four Steps to GHS Compliance. PMID- 26887084 TI - Taking the Work Out of Reward and Recognition: Using Wellness, Safety, and Performance Incentives. PMID- 26887085 TI - Taking Stock of 2015. PMID- 26887086 TI - Solving Employee Transportation Issues. PMID- 26887087 TI - Comfort is the Key to FR Clothing Compliance. PMID- 26887088 TI - Gearing Up for the Race Against Time. PMID- 26887089 TI - Prepare for the Worst and Then Be Ready When It Happens. PMID- 26887090 TI - Training By the Book. PMID- 26887091 TI - No Strain Safety. PMID- 26887092 TI - Unmet clinical needs in cervical cancer screening. AB - Cancer rates worldwide are expected to increase disproportionally in coming decades relative to the projected increase in population, especially in the developing world. The general unavailability of the Pap test and the cost of the HPV test in the developing world have precluded the deployment of effective cervical cancer screening programs in many developing countries. Recent improvements in testing technology arise from a need to overcome the significant limitations of the Pap test and HPV test, but results require first-world technology and validation. Developing countries, where cervical cancer remains one of the most important causes of cancer death, have the greatest need for an affordable, easy-to-use, and highly reliable cancer screening method that can return a diagnosis through efficient laboratory analysis or, more easily, at a woman's point of care. While research, testing, and vaccine improvements in recent years continue to lower the incidence of cervical cancer in some developed countries such as the U.S., HPV testing research needs to do more than test for the presence of virus. The tests must determine the presence and progression of cervical disease. Tests should be more sensitive and specific than Pap tests and Pap-related tests, and should be accurate in more than 90 percent of cases. Tests also need to be low-cost, objective, and easy to perform so screening programs can be widely implemented in developing countries where the need for a better cervical cancer screening test is highest. Such tests may be available through the recent advances in specific biomarkers of cervical cancer and multiplex detection technologies. Development of the next generation of cervical cancer tests that are more specific, sensitive, and informative than the traditional Pap or HPV test will make a significant impact on the reduction of cervical cancer worldwide. PMID- 26887093 TI - The evolution of prenatal testing: how NIPT is changing the landscape in fetal aneuploidy screening. PMID- 26887094 TI - Beyond conventional cell analysis: the latest science and technology in flow cytometry. AB - Combining powerful performance and innovative design and technology, it is possible to deliver a compact, easy-to-use flow cytometry system. Pushing the 'norms' of conventional flow cytometry, today's--and tomorrow's--systems enable complex research into high-content applications in cell biology, as well as a deeper understanding of the advantages gained from the emerging nanoparticle frontier. Flow cytometry is a powerful tool for interrogating complex biological questions at the forefront of biomedical and life science research and increasingly for clinical laboratory applications. Today's investigators want to harness that power and are demanding smaller and more powerful instruments that are more affordable and easier to use. Using innovation, engineers are able to deliver solutions to meet the challenge. PMID- 26887095 TI - Liquid biopsy: the time is even more right! PMID- 26887096 TI - In the news: antibiotic resistance. PMID- 26887097 TI - Co-creating critical limits for enhanced acute care: proven need and web knowledge base. Part 2: Standard of care, what it means and how it is applied. PMID- 26887098 TI - What's the buzz in drug testing? PMID- 26887100 TI - Change Is the Name of the Game. PMID- 26887101 TI - Adherence to Oral Agents for Cancer. The Nurse's Role in an Evolving Phenomenon. PMID- 26887102 TI - How Can Nurses Help Patients Adhere to Their Oral Chemotherapy?. PMID- 26887103 TI - Oncology Nurses Can Use Evidence to Promote Oral Adherence. PMID- 26887104 TI - Growing Number of States Enact Right-to-Try Laws in Challenge to FDA. PMID- 26887105 TI - How to Manage the Side Effects of New Targets Agents for Metastatic Colorectal Cancer. PMID- 26887106 TI - FDA Claims Jurisdiction Over Premarket Tobacco Product Applications. PMID- 26887107 TI - The Case of the Looming Medical Bankruptcy. PMID- 26887108 TI - Aspirin Post-Diagnosis for Gastrointestinal Cancer Linked to Improved Survival. PMID- 26887109 TI - GASTROESOPHAGEAL REFLUX DISEASE IN ASSOCIATION WITH LIPID-METABOLIC INDICATORS AT THE YAKUTSK. AB - AIM: To estimate interrelations of gastroesophageal reflux disease with lipid metabolic indicators at the Yakutsk. MATERIALS AND METHODS: A one-stage investigation of 100 patients of the Yakut nationality with gastroesophageal reflux disease (GERD) is carried out. For estimating the association of GERD clinical symptoms with lipid-metabolic indicators a method of binary logistical regress with compulsory inclusion of predictors has been used. RESULTS: According to results of the comparison most statistically significant distinctions of metabolic indicators are revealed at GERD esophageal (eructation) and extra esophageal symptoms (night cough), dyspepsia (distention, epigastric heaviness), as well as snoring. Logistical regression analysis has confirmed interrelation of clinical symptoms with lipid-metabolic indicators, as waist circumference, a level of arterial pressure and blood lipid (triglycerides, lipoprotein cholesterol of low and high density). CONCLUSIONS: Thus, the estimation of interrelation of GERD clinical symptoms with MS criteria at the Yakutsk has revealed the influence of MS components, especially abdominal adiposity, arterial hypertension and triglycerides on the development of dyspepsic symptoms (distention, epigastric heaviness), GERD esophageal (eructation) and extra esophageal manifestations (night cough). PMID- 26887111 TI - ADAPTIVE REACTIONS OF INDIGENOUS POPULATION OF YAKUTIA. AB - INTRODUCTION: The researches of organism's adaptive possibilities of indigenous population of the Arctic region are extremely important in modern conditions of the development of northern territories. The functional reserve of basic physiological systems and their interaction define "the health's resources", its potential level. AIM: This research has substantiated the adaptive reactions of organism of the North inhabitants on the basis of medical-physiological results. MATERIALS AND METHODS: Physical development was estimated by the standard anthopometrical method: the height and body mass were measured, index of body mass (BM), Quetelet's index, Rohrer's index were defined, area of body surface was calculated. Carbon dioxide in the air was defined by portable infra-red gas analyzer of firm "Fudji" for measurements indoors and outdoors. The parametres of blood acid-base state (ABS) were analyzed by standard procedures with microevaluator application ABL-330 (Denmark). Computer spirometry was done on the hardware-software diagnostic complex (HSDC) for analyses of external respiration function (NSRIMT - Russia) and "Pneumoscrin-2" of Erih Eger company (Germany). Arterial pressure was measured by Korotkov's method. RESULTS: The inhabitants of the North irrespective of ethnicity have conditions for more effective lung ventilation to satisfaction of the high metabolic requirements of the organism. CONCLUSIONS: Stability of arterial pressure among indigenous population, microcirculation optimisation and transcapillary tissues exchange, conserves steady level of metabolism that testifies a high level of adaptation of the person to severe climate- geographic North conditions. PMID- 26887110 TI - FEATURES OF CLINICAL-FUNCTIONAL MANIFESTATIONS OF CHRONIC OBSTRUCTIVE LUNG DISEASE IN COMBINATION WITH METABOLIC SYNDROME IN ETHNIC GROUPS OF THE YAKUTS AND THE RUSSIANS. AB - AIM: Studying features of clinical-functional manifestations of chronic obstructive lung disease in the combination with metabolic syndrome in the Yakut ethnic group. MATERIALS AND METHODS: The basic group consisted of 39 patients of Yakut nationality with chronic obstructive lung disease (COLD) in the combination with metabolic syndrome (MS), middle age of them being 53.4 +/- 1.17 years. The comparison group comprised 40 patients of Russian nationality with COLD and MS with middle age 53.1 +/- 1.21 years. Features of clinical manifestations and respiratory functions are studied. RESULTS: Cough and sputum were noted in dynamics for 3 years by 64.1% of Yakut patients and 85% of the Russians, p = 0.033; the intensity of cough was marked at 30% of patients of Russian nationality and 15.4% of patients of the Yakut nationality, p = 0.01 6. The morning sputum and daily sputum within 3 months a year at the Russians in comparison with the Yakuts was marked in 95 % vs 74,4 %, p = 0.011; 80.0% vs 56.4% p = 0.024, accordingly. According to Medical Research Council (mMRC) Dyspnea Scale (Mahler et al., 1985) dyspnea has been 2.2 +/- 0.09 points atthe Yakuts vs 2.7 +/- 0.09 points at Russian, p = 0.002. At patients of the Yakut nationality more often exacerbations were registered 2 times a year (53.8%), at patients of Russian nationality noted 3 times a year (55%). Respiratory function manifestations have been at patients of the Yakut nationality with COLD and MS, in comparison with similar Russian patients: forced expiratory volume for a first second (FEV,) - 64,0+2,30 % vs 56,8?2,69 %, p = 0,026; forced vital capacity of lungs (FVC) - 65,0?2,45 vs 65,0?3,70, p = 0.733; FEV1/FVCL ratio being 102.5 +/- 2.81 vs 87.3 +/- 3.30, p = 0.000, accordingly. CONCLUSIONS: Regardless of ethnicity the phenotype "D" has higher prevalence rate of clinical phenotype COLD in the combination with metabolic syndrome, thus at the Russians the clinical COLD is characterized by severe clinical manifestations in comparison with theYakuts, and also in both ethnic groups expiratory dysfunctions in the form of decreasing FEV1, decreasing FVC and increases of ratio FEV1/FVC > 70% are marked. PMID- 26887112 TI - THE ROLE OF VIRAL HEPATITIS IN THE MECHANISM OF LIVER CANCER FORMATION AMONG THE FAR NORTH INDIGENOUS INHABITANTS. AB - INTRODUCTION: Yakutia is a region of high prevalence of viral hepatitis B, C and D. The rating and ranking of risk factors for the formation of cirrhosis and primary liver cancer in patients with chronic viral hepatitis (CVH) B, C and D in the Republic of Sakha (Yakutia) (R S(Y)), it is a serious medical problem. AIM: Studying of the main reasons for the progression of chronic viral hepatitis B, C and D to cirrhosis and liver cancer in the Far North. MATERIALS AND METHODS: Materials of official statistics of theTerritorial Rospotrebnadzor and official registration of the Ministry of Health of RS (Y); serological and molecular biological research methods to the studying of HCV genotype B, C, D. RESULTS: On the basis of long-term morbidity of chronic viral hepatitis B, C and D and their outcomes in Yakutia defined a role in the progression to cirrhosis and primary liver cancer, ethnicity and genotype of HBV and HDV. Established fact of viral replication in cirrhosis and primary liver cancer under adverse social and environmental factors, genetically determined increased concentration of acetaldehyde due to impaired activity of alcohol dehydrogenases (ADH) and aldegiddegirogenases (AIDG) at the indigenous inhabitants of the republic proves the need for targeted therapy of complex events. CONCLUSIONS: The regions of Yakutia are the most affected by the virus of hepatitis B, C and D with progressive course of the disease to cirrhosis and cirrhosis liver cancer, defined by genotype hepatitis B & D, in which significantly usually occurs primary liver cancer, also noted that the combined mixed-replicating virus hepatitis is a risk factor for primary liver cancer. PMID- 26887113 TI - PSYCHOLOGICAL AND VEGETATIVE CHARACTERISTICS OF STUDENTS--YAKUTS WITH DIFFERENT EDUCATIONAL SUCCESS. AB - Consideration of ethnic features of adaptation of students to educational activity in high school is needed as to optimize the learning process and to preserve the functional reserves of the organism. We investigated the characteristics of the psychological status and correlated them with the heart rhythm variability in students Yakuts with varying different effectiveness of educational success. Regression analysis of the relationship of personality psychological characteristics of students with indicators of the spectral power of heart rate showed that more adaptive resource autonomic regulation of the heart have people with an average level of introversion and of personal anxiety indicators corresponding to the transition from moderate to high degree and also in individuals with an average levels of neuroticism. Revealed higher effectiveness of examinations students introverted compared to extroverts and students with high personal anxiety relatively to persons with moderate personal anxiety. High efficiency of intellectual activity of students is achieved through high tension mechanisms vegetative regulation of the heart. PMID- 26887114 TI - BREADTH SPREADING OF VIRAL HEPATITIS MARKERS IN THE RISK GROUPS IN THE REPUBLIC OF SAKHA (YAKUTIA). AB - INTRODUCTION: Republic of Sakha (Yakutia) is a hyperendemic region of Russian Federation for spreading of parenteral viral hepatitis B, C and D. In risk groups of these diseases are firstly medical personnel, who contacting with infection carriers including latent infections family and members of families of chronic viral hepatitis carriers. AIM: To reveal the breadth of spreading of viral hepatitis markers in the risk groups. MATERIALS AND METHODS: The level of HBV- and HC- infection were determined in medical staff of large multi specialty hospital and family members of people with viral hepatitis B and C. Epidemiological, clinical, serological and molecular biology methods of viral hepatitis diagnostics were applied in this study. RESULTS: Results of this study showed that the staff at surgery and hematology departments and all nursing staff belong to the high-risk of HBV-infection groups. Therefore, they are a priority for active immunization. Attention is paid on the fact that infectivity of medical staff is not equally distributed in dependence on type of department and position of medical staff. Rate HBV-marker detecting in "family hearths" was dependent on degree of interrelationship with infection source. According received information, in families of patientwith chronic hepatitis B spreading of infection was higher (77.6%) then in families of patients with acute hepatitis B (39.7%). At primary examination of families an anti-HCV was detected in 9.3 +/- 1.8% cases, i.e. the spreading of HCV was at low-activity. CONCLUSIONS: Results of our study on spreading of hepatitis B and C in Yakutia showed the high rate of appearance of HCV and HBV markers in the risk groups. PMID- 26887115 TI - LICHENS' B-OLIGOSACCHARIDES IN THE CORRECTION OF METABOLIC DISORDERS IN TYPE 2 DIABETES MELLITUS. AB - INTRODUCTION: Lichens of the genus Cladonia are used as medicinal plants in folk medicine. Biologically active food supplement (BAFS) on the basis of lichens p. Cladonia was derived by mechanical-chemical biotechnology in the Educational Research-Engineering Laboratory "Mechanical-Chemical Biotechnology" of the North Eastern Federal University (NEFU). As a result of biotech impact, the solid beta glycoside bonds are destructed on beta-oligosaccharide molecules, and other groups of lichen BAS is mobilized. The content of hydrolysable carbohydrates in samples of lichen increased 8 times after mechanical activation. AIM: The aim of investigation was to study the effects of BAFS "Yagel-Detox" in patients with type 2 diabetes mellitus (DM 2). MATERIALS AND METHODS: The 150 patients (group 1 -100 patients receiving "Yagel-Detox", group 2--50 patients receiving placebo) with a diagnosis DM 2 were examined. The research included: general clinical and instrumental examination, biochemical and clinical blood tests. "Yagel-Detox" was used 1 capsule 3 times a day, the rate of admission was 3 months. RESULTS: Clinical trials have shown that 3-month intake of BAFS "Yagel-Detox" reduces the concentration of blood glucose 1.3 1.6 times (in the control group--1.2 / 1.4 times), glycosylated hemoglobin--from 9.8 / 11.4% to 7.6% (in the control group- 1.0%). The concentration of low-density lipoprotein (LDL) reduced on 1.3% through 6 months. Patients of both groups were on the similar tablet glucose-lowering therapy (randomized treatment), which have not been adjusted. CONCLUSIONS: The obtained results allow us to recommend BAFS "Yagel-Detox" as an additional remedy to normalize blood glucose concentration in patients with DM 2. PMID- 26887117 TI - NEW APPLICATIONS OF ADAPTOGENS TO REDUCE RADIATION SIDE EFFECTS. AB - One of the live medical issues today is to find medication to prevent adverse effects of ionizing radiation on the immune and hematopoietic systems. In Yakutia where in most of its regions the overall environmental situation is getting worse due to the development of natural deposits including radioactive deposits, this problem remains vital. The purpose of this work is to study radioprotective properties of adaptogens in the case of the hematopoietic system under irradiation. The studies were conducted on certain groups of hybrid mice. We used the methods of radiation exposure by a radiological apparatus RUM-25 on hybrid mice followed by studying the cellularity of bone marrow, spleen and thymus. The functional activity of all compartments of early hematopoiesis (bone marrow hematopoiesis) was identified by the exogenous colony forming method. The study found that the extracts of reindeer and moose antlers have a stimulating effect on the functional activity of the hematopoietic precursors in response to radiation. The study medication stimulates regeneration processes in the thymus and bone marrow after irradiation. Further, the adaptogens stimulatory effect on CFU functional activity was identified. The most pronounced effect has the extracts of reindeer antlers "Epsorin". PMID- 26887116 TI - CLINICAL AND MORPHOLOGICAL CHARACTERISTICS OF THE CHRONIC GASTRITIS WITH FUNCTIONAL DYSPEPSIA IN THE REPUBLIC OF SAKHA (YAKUTIA). AB - INTRODUCTION: Chronic gastritis with syndrome, functional dyspepsia (SFD) is one of the most pressing problems in medicine. Certain scientific and practical interest is the elucidation of the frequency and clinical manifestations of functional dyspepsia in patients hospitalized in the gastroenterology department YAGKB and frequency combinations of chronic gastritis (including H. pylori) with functional dyspepsia. AIM: The aim of the study was to investigate the clinical and morphological features of the chronic gastritis with syndrome pattern of functional dyspepsia in native-born and people of the Republic of Sakha (Yakutia), and to assess the effectiveness of treatment, depending on the gastric acid and H. pylori. MATERIALS AND METHODS: This study examined 105 patients with functional dyspepsia, including 41 patients with epigastric pain syndrome and 64 patients with postprandial distress syndrome. Considered groups of patients were homogeneous for age, gender, by ethnicity. Of the 105 patients included in the study, I group were 57 indigenous people (80% of them--Yakutia), 11 group--48 people visiting (Caucasians). RESULTS: Clinical presentation and course of chronic gastritis with functional dyspepsia in the Republic of Sakha (Yakutia) have a number of distinctive features: epigastric pain syndrome occurs in 26.8% of patients and 73.2% of the indigenous population of the visitor, the intensity of pain in the root is much lower than that of visitors--12 and 85% respectively. Postprandial distress syndrome was diagnosed in 71.9% of patients and 28.1% of the indigenous newcomers. At endoscopy in all patients with functional dyspepsia diagnosed chronic gastritis. The native inhabitants of the most common mixed gastritis (54.5%), the newcomers--superficial gastritis (66.7%). CONCLUSIONS: The found features of a current of functional dyspepsia can be further the basis for the individualized and differentiated approaches to treatment of this disease. PMID- 26887118 TI - THE SITUATION WITH STAFFING IN PEDIATRIC SERVICES OF THE REPUBLIC OF SAKHA (YAKUTIA). AB - INTRODUCTION: At present, the public health in the Republic of Sakha (Yakutia) (RS(Y)) is a powerful state structure with an extensive network of prevention and treatment facilities. Since medical service density is the most generalized criterion of the medical service level, its analysis represents special interest to any regional system of public health. AIM: To analyze the dynamics of availability of doctors of all fields, of pediatricians, including pediatric surgeons, pediatric endocrinologists, and pediatric oncologists in 1995-2013. MATERIALS AND METHODS: The analysis is done to reveal the dynamics of availability of doctors: of all fields, pediatricians, including pediatric surgeons, pediatric endocrinologists, and pediatric oncologists to the population of Yakutia in 1995-2013. A statistical and comparative analysis of the data has done. RESULTS: As a whole, in the studied period, RS(Y) witnessed an increase in the availability of doctors of the pediatric profile to the child population. Both in the Russian Federation and in the RS(Y) in particular, the increased availability of pediatricians was mainly due to the reduction of the child population and, to a lesser degree, to an increase in the number of doctors. CONCLUSIONS: The survey revealed the increased availability of pediatricians in RS(Y) only in densely populated areas and the continuing lack of pediatric services in the areas with low population density. PMID- 26887119 TI - MICROBIOCENOSIS IN INFLAMMATORY PROCESSES OF MARGINAL GUM AMONG CHILDREN. AB - INTRODUCTION: The development of gingivitis among children remains actual problem in modern dentistry due to high prevalence, disorders of dental-alveolar functions and development of parodontium diseases at the older age. The microorganisms occupying dental chamfer play the leading role in parodontium tissues damage. AIM: Research of microbial spectrum of dental chamfer and assessment of etiology significances of the revealed microorganisms in gingivitis among children of school age. MATERIALS AND METHODS: Bacteriological research of dental chamfer in 30 children of secondary school age with gingivitis of slight and severe level. Inoculations have been done on the chocolate agar incubated in air-locked containers with gas generators for anaerobic atmosphere "GENbag Anaer" and inoculations on bloody gemagar--with gas generators for microaerophiles "GENbag Microaer" (bioMerieux) within 24-48 hours. Infections were precipitated out on the Saburo medium. Identification of discharged cultures was carried out on the microbialogic evaluator "Vitek II Compact" (bioMerieux). RESULTS: Microflora of dental chamfer in the examined children has been presented by three groups of microorganisms: gram-positive cocci (63.3%), gram-negative nonfermentative bacteriums (63.3%) and yeast Candida fungus (30%). Among gram postitive cocci representatives of normal microflora of oral cavity Streptococcus oralis (26.6%) were dominated. Neisseria (N. sicca, cinerea et animaloris) were dominated most often in the group of gram-negative nonfermentative bacteriums (23.3% of children), yeast Candida fungus have been presented by two kinds--C. dubliensis (at 20% of children) and C. albicans (at 10%). The mean content of all discharged microorganisms has compounded 5,7 Ig KOE that supposes their etiology role in development of marginal gum inflammation. CONCLUSIONS: Received results showed us some mechanisms of development of inflammatory diseases of parodontium tissues which will allow us to develop new approaches of treatment and gingivitis prevention among children of school age. PMID- 26887120 TI - THE ANALYSIS OF MAJOR RISK FACTORS OF CARDIOVASCULAR DISEASES AMONG INHABITANTS OF THE NORTH REGION. AB - Last years the problem of organism's adaptation to severe climate-environmental conditions of the Far North has been intensively developed. The Republic of Sakha (Yakutia) is the most northern republic of the Russian Federation. People have created a unique way of life, language, original culture on this cold part of the earth and have carried centuries later. This unique experience has been saved up throughout many centuries and generated in natural environment of habitation and passed from generation to generation. Last years the changes of living conditions of indigenous population, urbanization and globalisation, deterioration of ecological conditions exhausted reserve possibilities of organism. Among the indigenous population health change has menacing character, especially among the children's population. The analysis of major risk factors of the development of cardiovascular diseases among the indigenous population of the north has been carried out in this research. PMID- 26887121 TI - EPIDEMIOLOGICAL FEATURES OF CHRONIC VIRUS HEPATITIS B AND C IN THE REPUBLIC SAKHA (YAKUTIA). AB - High disease burden of chronic virus hepatitis B and C of population in the Republic Sakha (Yakutia) is subject to referring it to endemic territories due to these infections. For a 15-year-old period the disease has been registered at higher rates in the Russian Federation. PMID- 26887122 TI - CHARACTERISTIC OF ACTUAL FOOD AT ELDERLY AND SENILE AGED POPULATION OF YAKUTIA. AB - AIM: To conduct estimation of actual food among in digenous and arrived population of Yakutia of elderly and senile ages. MATERIALS AND METHODS: In the work results of epidemiological research with analysis of actual food of the population of Yakutia at the age of 60 years and over are presented. On the basis of a list of candidates with use of random selection a representative sample of men and women of Yakutsk at the age of 60 years and more has been generated. In total 775 foreheads were surveyed, the middle age has made 75.7 +/- 9.4 years. For the analysis of actual food 575 people (244 men and 331 women) have been included. Among the surveyed there were 244 respondents of the in digenous population (the Yakuts) and 331 arrived respondents (the Russians, the Ukrainians, the Byelorussians, the Poles, the Germans, the Jews). The estimation of actual food is conducted by means of a frequency questionnaire. RESULTS: High content of general fat, sated fat acids, polyunsaturated fat acids and refined sugar due to low consumption of general carbohydrates is revealed. At the analysis of food package of the indigenous population in comparison with the newly arrived some distinctions in consumption of following products are revealed: fresh, tinned and frozen vegetables, potatoes, eggs, horsemeat, venison, koumiss, fresh fruit and berries, oil and fats, bean, juice and drinks, sugar, chocolate and confectionery products. CONCLUSIONS: daily food intake of the indigenous population of elderly and senile ages is notable for lower daily caloric content, greater general fat, SFA, less consumption of refined sugar on the background of significantly lower content of general carbohydrates, starch and food proteins. In diets at theYakuts there is considerably lower consumption of fresh and tinned vegetables, potatoes, eggs, fresh fruit and berries, bean, nuts, sugar, chocolate and confectionery products and higher consumption of meat products (horsemeat, venison), oil and fats. PMID- 26887123 TI - RESULTS OF COLON CANCER SURGICAL TREATMENT. AB - In recent decades in the Republic of Sakha (Yakutia) there was a growth of the colon cancer, so the problem of its early diagnosis and treatment currently acquired great importance. The article is devoted to one of the most common cancers--the colon cancer and considers issues of the differentiated approach to its integrated treatment. We achieved the best results of the five-year survival in patients with colon cancer at Stage A. PMID- 26887124 TI - GENDER FEATURES OF THE ANTHROPOMETRIC, CEPHALOMETRIC AND BIOIMPEDANCE PARAMETERS IN THE STUDENTS OF YAKUTIA. AB - To establish the anthropo-ecological portrait of the current population of Yakutia, it is necessary to study the regularities of the variability of physical status in different gender groups and develop regional standards of the physical development of different age-sex groups of the population with regard to the peculiarities of the environment. The aim of this study is to do research on the gender features of anthropometric, cephalometric and bioimpedance parameters in the students of Yakut ethnicity. The measures of 228 Yakut girls and 168 Yakut youths born and permanently resident in Yakutia were analyzed. Anthropometric measurements were performed using the method of V.V. Bunak (1941), somatotyping- using the Rees-Eysenck index (1945). Head type was determined by the cephalic index, face type--by the upper facial index. Bioelectrical impedance analysis with the use of ABC--01 Medass analyzer was performed to estimate body composition. Adipose tissue mass (AM), skeletal muscle mass (SMM), lean mass (LM), active cell mass (ACM) and phase angle (PA) were determined. Obtained material was processed by the method of variation statistics with the use of SPSS 17.0 software package. Overall measures of the soma of the examined groups have gender features of body organization that are expressed in the significantly higher values of all measured parameters in the youths of Yakutia. In our study, the sexual dimorphism in the distribution of somatotypes by the Rees-Eysenck index has not been identified. The analysis of cephalometric measures has revealed reliably higher parameters of absolute head sizes in the youths. Gender differences in the distribution of head and face types have not been found in the examined ethno-age group. Significantly larger absolute amount of AM has been established in the girls. The measures of SMM, ACM and LM are reliably higher in the youths. The values of active and reactive tissue resistance are reliably higher in the girls. Gender features of the anthropometric, cephalometric and bioimpedance parameters of the students have been established. The conducted study presents the anthropo-ecological image of this age-sex group of the population of Yakutia. PMID- 26887125 TI - CLINICAL SIGNIFICANCE LEVELS OF C-REACTIVE PROTEIN AND CERULOPLASMIN IN PATIENTS WITH ISCHEMIC HEART DISEASE. AB - INTRODUCTION: The study examined the relationship of levels of ceruloplasmin and CRP in patients with coronary heart disease and assessed the possibility of their use for diagnosis and prediction of developing complications. AIM: The study investigated the relationship of levels of ceruloplasmin and CRP in patients with coronary heart disease and their potential use in the diagnosis and prediction of complications. MATERIALS AND METHODS: Examined 117 patients with ischemic heart disease at the age of 39 to 80 years (median age + 13.9 61.7 years), among them 56 were women and 61 men. Assessment of prognosis in patients with ischemic heart disease was conducted based on the two-year observation. RESULTS: The reverse relationship between the levels of ceruloplasmin and CRP was identified. When comparing the survival curves without adverse events using the log-rank analysis in patients with levels of CPU of more than 0.2 grams per liter and CRP of less than 6.0 mg/l, the prognosis was significantly better than in patients with simultaneously detected low levels of the CPU (less than 0.2 g/l) and high levels of CRP (more than 6.0 mg/l) in the blood (p < 0.05), CONCLUSIONS: Highly sensitive measurement method of levels of c-reactive protein in patients with coronary heart disease combined with measurement of levels of ceruloplasmin, gives an opportunity to assess the activity of vascular inflammation that can be used to predict the development of acute coronary events. PMID- 26887126 TI - SUPER EARLY PREMATURE BIRTH IN TERMS OF THE NEW STANDARD OF LIVE BIRTH IN THE REPUBLIC OF SAKHA (YAKUTIA). AB - Premature birth is a serious problem of public health around the world owing to the high frequency of complications and perinatal losses. According to the WHO recommendations by gestation terms the premature birth divides into: super early premature birth (SEPB) in the term of 22-27 weeks, early PB in the term of 28-33 weeks and PB in the term of 34-37 weeks. Preterm born infants make 85%, and in the neonatal mortality structure make more than 55%. It is necessary to consider that in recent years the number of women in the premature birth development risk group has increased, to which patients with a uterus scar, extragenital pathology, supporting reproductive technology treatment pregnancy are related. PMID- 26887127 TI - MORPHOLOGICAL ASSESSMENT OF NATIVE MALE SUBJECTS' THYROID BODY IN THE REPUBLIC SAKHA (YAKUTIA) IN DIFFERENT SEASONS. AB - Morphological analysis of macro-, microstructures of native male subjects' thyroid gland in the Republic Sakha (Yakutia) in different seasons has been conducted. Macromorphometric indicators of native male subjects' thyroid gland (specific weight, total capacity, linear indicators were specified in summer and winter seasons. Micromorphometric characteristics of structural components of native male subjects' thyroid gland tissue was given in relation to different seasons. In this case native male subjects' thyroid gland was as curtained as normoplastic mixed type of structure, indicators of outer and inner thyroid gland follicles diameter in winter period were slightly bigger than in summer period. The same tendency was observed when thyroid gland follicular-colloidal index was calculated. On the data obtained the attempt to assess season temperature factor impact on the thyroid gland structural indicators were made. This assessment might be used as morphological equivalent of the body adaptation processes in northern regions. PMID- 26887128 TI - X-RAY DENSITOMETRY AND FRAX MODEL IN PREDICTING THE RISK OF OSTEOPOROSIS AND LOW ENERGY FRACTURES IN POSTMENOPAUSAL WOMEN. AB - 88 people of 50 years of age and older were put in this cross-sectional study. The main risk factors for osteoporosis and bone fractures were obtained using questionnaires. X-ray absorptiometry of the distal forearm was carried out with the help of Osteometer DTX-200. The FRAX tool was used for calculation of the 10 year absolute risk of major osteoporotic fractures. In the 50-59 year age group osteoporosis was found only in 30% of women but with increasing age its occurrence increases dramatically approaching 70% in women 70 years of age and older. The higher the age of women, the lower bone mineral density (r = -0.44, p < 0.001). PMID- 26887129 TI - REGIONAL TRENDS IN THE WORKING-AGE POPULATION MORTALITY RATE IN THE REPUBLIC OF SAKHA (YAKUTIA) IN 1990-2012. AB - Regions of the Russian Federation differ in climatic-geographic, medical demographic and social-economic situations. One of the regions with distinct peculiarities is the Republic of Sakha (Yakutia). Ranking first by the territory (3,103.2 thousand sq x km), Yakutia is on the 81th place by the population density among regions of the Russian Federation (0.3 people per 1 km2).Yakutia is one of the most isolated and inaccessible regions of the world: 90% of the territory lacks all-the-year-round transportation. Regions of the republic, as well, differ significantly in the climatic conditions and the levels of social economic development, which influences the population health indicators, including mortality. This survey aimed to study the trends of mortality in the working-age population in different groups of regions. To do this, basing on the statistical data, we compared the levels, trends and structure of mortality in 1990-2012. It was established that the different groups of regions show a significant variation in the working-age population mortality, depending on the social-economic conditions. Since 2000, the Arctic group of regions has demonstrated higher mortality in working-age men and women, especially of cardiovascular and digestive system diseases, and external causes. Lying beyond the Arctic Circle, these regions have severe conditions and a relatively low level of social-economic development. As for the rural regions, despite the relatively favourabe situation, they also show a high level of mortality of external causes. The industrial regions are characterized by higher social economic development, better transport infrastructure, a satisfactory material base of medical institutions. They also have sufficient resources of health institutions, including the staff and modern equipment for treatment and diagnostics, as well as, which is critical, the full range of medical specialists. Thus, these regions demonstrate lower population mortality; however, there is still mortality of infectious diseases, neoplasms, and respiratory diseases. PMID- 26887130 TI - ADAPTIVE MECHANISMS OF THE IMMUNE SYSTEM IN CHILDREN IN FAR NORTH. AB - This article is devoted to the probleme of modern Pediatrics pathology of the immune system in children with complicated viral infections. The aim of this study was to investigate the immune and cytokine status in children with complicated acute respiratory viral infections. The study included 100 children are often ill respiratory virus infections (more than 8 times per year) from age 0 to 7 years, and 30 children with upper respiratory tract infection; no more than 1 time per year-the control group. The standards of indicators developed by the staff of Immunological laboratory Diagnostic center of the Ministry of health of Republic Sakha (Yakutia ) together with the Institute of health of the Republic Sakha (Yakutia). Statistical calculations made on the basis of applied programs "SAS"and "SPSS"In the analysis of contingency tables (estimates of the correlation of the characteristic and evaluation of significance of differences between groups) used the criterion of 2 (Pearson and likelihood ratio and Fisher's exact test. Comparison of mean values was performed univariate analysis of variance using T-student criterion for assessing the equality of mean F-Fisher test to assess equality of variance. Extreme climatic conditions ofthe far North have an impact on immunological mechanisms. In the analysis of changes ofthe immune status revealed the greatest decline in T-cell level and components of complement in children with complications of viral respiratory infections. In children with complicated respiratory viral infections reduced cellular immunity (CD3+, CD41, CD81, CD+, CD 22+). In children with complicated respiratory viral infections decrease levels ofcytokines (IFN-y FN0-d), indicating about the risk of the formation of complications of respiratory viral infections. As a result of drug therapy of broncho-vaxom marked improvement in immune status and the absence of recurrence of respiratory viral infections within the next 3 months after therapy. PMID- 26887131 TI - IMMUNOHISTOCHEMICAL ANALYSIS OF MAMMARY EPITHELIAL CELLS AT TUMORAL GROWTH IN REPUBLIC OF SAKHA (YAKUTIA). AB - The analysis of results histological examination of surgical material of breast cancer from 294 women with subsequent immunohistochemical determination of estrogen (ER)--and progesterone (PgR)--receptors, proliferative activity (Ki-67), expression of the mutant suppressor gene (p53) and gene-inhibitor apoptosis (bcl 2) was carried out. The obtained data testify that IHC-research of the tumor progression markers is a defining part in the forecast of course, optimization of therapeutic approaches with an individualization of chemo-, hormonal and beam therapy of mammary cancer, the decision of a question of medicamentous and/or surgical shutdown of the ovaries, based on the research results of the biological activity markers of the tumor. PMID- 26887132 TI - THE ROLE OF CANDIDA IN INTESTINAL DYSBACTERIOSIS FORMATION. AB - INTRODUCTION: In modern TB chemotherapy until today retains a leading role in the treatment of tuberculosis patients, and specific nature of the inflammatory process, its course and symptoms include the duration and continuity of chemotherapy. It is known that prolonged chemotherapy naturally leads a large majority (92.0%) of patients in the development of intestinal dysbiosis, where the leading role in the microbial imbalance is a deficiency or complete absence of bifidobacteria, it creates conditions for the settlement of fungi Candida, also plays a major role in microbial associations. AIM: Examine the role of candida in intestinal dysbacteriosis formation. MATERIALS AND METHODS: The 500 patients with various forms of pulmonary tuberculosis were examined for reveal intestinal dysbiosis, which conducted bacteriological examination of feces for intestinal dysbiosis method RV Epstein-Litvak FL Vilshanskoy. RESULTS: In great majority of patients (92%), the long chemotherapy naturally leads to conclusions development of intestines dysbacteriosis. The leading value in a microbial imbalance belongs to deficiency or total absence of the bifidobacterium, which creates conditions for Candida, and plays the main part in microbial associations. There was noted a high therapeutic efficiency of the pathogenic agents antifungal drugs, allowing to eliminate Candida intestinal dysbacteriosis of patients suffered from pulmonary tuberculosis. PMID- 26887133 TI - RESULTS OF MONITORING METALLO-BETA-LACTAMASE-PRODUCING STRAINS OF PSEUDOMONAS AERUGINOSA IN A MULTI-PROFILE HOSPITAL. AB - The authors present the results of long-term monitoring of metallo-beta-lactamase (MBL) producing strains of Pseudomonas aeruginosa in the Republican Hospital No 2 of Yakutsk, Russian Federation. Hospitals across Russia, as well as the rest of the world, face a rapid appearance and a virtually unchecked spread of multiresistant and panresistant nosocomial pathogens. Especially prevalent are multidrug-resistant isolates of P. aeruginosa, most often found among the patients of intensive care and intensive therapy units, as well as surgery departments. The aim of this study is to investigate the prevalence of metallo beta-lactamase-producing strains of P. aeruginosa in a multi-profile hospital. 2,135 isolates of P. aeruginosa were studied, collected during a time span of seven years (2008-2014) from clinical specimens of hospitalised patients in acute surgery, purulent surgery, neurosurgery, otolaryngology, coloproctology departments, intensive care and intensive therapy, burn units, as well as intensive care unit for patients with acute cerebrovascular accidents and coronary care unit. Strains were identified and re-identified using established methods, NEFERMtest 24 (MICROLATEST) biochemical microtest and API (bioMerieux) test systems were used. For all carbapenem-resistant strains a phenotype screening for MBL was performed using the double-disks method with EDTA. In order to identify VIM-type and IMP-type MBL genes a real-time multiplex polymerase chain reaction was used. Among the investigated strains the largest number of P. aeruginosa - 35.6% (761 isolates) was found in patients at intensive care and intensive therapy units. Clonal expansion of extensively drug-resistant strain P. aeruginosa ST235 (VIM-2) was determined, the resistance mechanism of which is connected to MBL. Sensitivity determination of MBL-producing isolates of P. aeruginosa has shown that isolated strains have a high level of resistance (100%) to all tested antibacterial agents: piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, cefoperazone-sulbactam, aztreonam, imipenem, meropenem, doripenem, gentamicin, netilmicin, amikacin, ciprofloxacin, levofloxacin, fosfomicin. PMID- 26887134 TI - THE ROLE OF MEDICAL AND SOCIAL FACTORS IN PREDICTING DISABILITY TUBERCULOSIS. AB - In persisting study are considered social, epydemiological and clinical features by sick tuberculosis lungs with for the first time installed by disability. On the grounds of got result are revealled main criteria of the forecasting to disability on tuberculosis lungs. Disability of pulmonary tuberculosis is an important medical and social problem and is dependent on the social and clinical factors. The study of disability reveals the main reasons for poor prognosis in tuberculosis, which leads to a more chronic course with frequent exacerbations and relapses. In Russia, the dynamics of disability for tuberculosis does not tend to decrease. Unfavorable epidemiological disability tuberculosis remains high in the structure of the primary disability in Yakutsk and Sakha (Yakutia) (2.8%, 2.5% - respectively). PMID- 26887135 TI - THE PREVALENCE OF CHRONIC VIRAL HEPATITIS IN CHILDREN AND ADOLESCENTS IN YAKUTIA. AB - Chronic hepatitis in children represents a serious health and social problem. Under the conditions of the high prevalence of viral hepatitis in Yakutia epidemiological process has a number of peculiarities. In children chronic hepatitis often occurs with minor clinical manifestations, which complicate diagnosis. The study of the epidemiological, clinical and laboratory data is an important task.The aim of the study was to investigate the epidemiological characteristics of chronic hepatitis in children and adolescents living in hyper endemic region. MATERIALS AND METHODS: The study included 1568 patients'data, registered in the dispensary with a diagnosis of chronic hepatitis in the period from 2000 to 2012. Epidemiological history data of 304 patients with chronic hepatitis were analyzed. The data from official statistics were used for epidemiological analysis. Processing of clinical and laboratory studies was performed using the statistical package IBM SPSS STATISTICS 19. RESULT: CH epidemiological features were identified, including the prevalence of HBV infection in etiological structure, the high incidence of the disease among the indigenous population, a high risk of intra-familial infection with hepatitis B virus , high frequency of perinatal infection with hepatitis C virus. It was proposed to maximize screening tests for markers of viral hepatitis and to improve quality control of vaccination. CONCLUSIONS: The epidemic process of viral hepatitis in children and adolescents in Yakutia is characterized by domination of HBV-infection in the structure of chronic hepatitis. The predominance of the indigenous nationalities among patients with chronic hepatitis B and the leading role of family contact in the routes structure of infection transmission indicates the importance of ethnic and social factors in contraction of the disease. PMID- 26887136 TI - DIAGNOSTICS ALGORITHM OF DIABETIC POLYNEUROPATHY IN PREDICTION OF CLINICAL COURSE. AB - AIM: To estimate the importance of new algorithm introducing of PDP diagnostics in practice of NEFU medical institute Clinic in detection of severity level and predicting of clinical course. MATERIALS AND METHODS: 50 people with sensory motor PDP form among patients with 2 type diabetes were examined on the basis of Clinic of NEFU medical institute. Patients have been divided into 2 groups by disease duration: the first groups were patients with duration of disease till 10 years, the second group--more than 10 years. Diagnostics methods: clinical neurologic, neurophysiological. RESULTS: Patients underwent polymodal sensitivity analysis, computer pallesteziometry, stabilometry, electroneuromyography. The dependence of clinical neurophysiological PDP parametres from severity of the duration of type 2 diabetes has been revealed. CONCLUSION: Thus, dependence of clinical-neurophysiological parametres of PDP severity from the duration of 2 type diabetes has been revealed. The new algorithm raised efficacy of clinical neurophysiological PDP diagnostics and helped the predicting of the clinical course. PMID- 26887137 TI - THE INFLUENCE OF URINARY TRACT INFECTIONS ON TREATMENT OF FRACTURE OF PROXIMAL FEMUR IN PATIENTS WITH SYSTEMIV OSTEOPOROSIS. AB - In the structure of intrahospital infections the infections of urinary tract make up from 20 to 40%. This problem represents special medical-social significance for trauma departments as patients with trauma are being in forced situation for along time. 380 patients older than 60 years (average age 73.6 +/- 9.2 years) with a fracture of proximal femur against background of the systemic osteoporosis having in-patient treatment in the trauma department of the Republic Hospital No2 were being examined and treated from 2011 to 2013. Urinary tract infections were diagnosed in 130 (34.2%) patients (average age 77.3 +/- 8.3 years). Women (80% 82%) with the average age 77.7 +/- 8.2 years prevailed by gender signs. From them 40 (30.8%) patients admitted with prehospital urinary tract infections and intrahospital urinary tract infections were diagnosed in 90 (69.2%) patients. In etiological structure of urinary tract infections the part of gram-negative microorganisms made up 47.4%, the leading role belonged to the family of Enterobacteriaceae. Escherichia coli (23.3%) and Klibsiella pneumonia (12%) were the most significant from them. Gram-positive microorganisms 44% were sown in the second place. More frequently Enterococci (33.6%) were separated such as Enterococcus faecium (18.1%) and Enterococcus faecalis (15.5%). Intrahospital urinary tract infections resistant to antimicrobial therapy were observed in 6.7% patients with systemic osteoporosis and fracture of proximal femur. The average duration of preoperative preparation and in-patient treatment of patients with fracture of proximal femurand concomitant urinary tract infections is much more (3.9 days and 5.4 bed-days correspondingly) higher than the average indications of all operated patients in the department. PMID- 26887138 TI - SIMULATION OF GENERAL ANESTHESIA ON THE "SIMMAN 3G" AND ITS EFFICIENCY. AB - In recent years in medical educational process new innovative technologies are widely used with computer simulation, providing the reality of medical intervations and procedures. Practice-training teaching with using of simulation allows to improve the efficiency of learning material at the expense of creating imaginary professional activity and leading barring material to practical activity. The arm of the investigation is evaluation of the students training efficiency at the Medical Institute on the topic "General Anesthesia with using a modern simulation "SimMan 3 G". The material of the investigation is the results, carried out on the basis of the Centre of Practical skills and medical virtual educational technologies (Simulation Centre) at the Medical Institute of NEFU by M.K. Ammosov. The Object of the investigation was made up by 55 students of the third (3) course of the Faculty of General Medicine of the Medical Institute of NEFU. The investigation was hold during practical trainings (April-May 2014) of the General Surgery Department on the topic "General Anesthesia". A simulation practical course "General Anesthesia" consisted of 12 academic hours. Practical training was carried out using instruments, equipments and facilities to install anesthesia on the SimMan 3G with shooting the process and further discussions of the results. The methods of the investigations were the appreciation of students background knowledge before and after practical training (by 5 points scale) and the analysis of the results. The results of the investigation showed that before the practical course only 23 students (41.8%) had dot positive marks: "Good"--7 students (12.7%) and "Satisfactory"--16 (29.1%) students. The rest 22 (58.2%) students had bad results. The practical trainings using real instruments, equipments and facilities with imitation of installation of preparations for introductory anesthesia, main analgesics and muscle relaxants showed a patients reaction on the virtual trainer SimMan 3 G. Students were divided into anesthetic team, co-assisting of an anesthesiologist, an assistant and nurses anesthetist, who conducted general anesthesia (the mask anesthesia, intravenous anesthesia, endotracheal anesthesia). After finishing the practical course 16 students (29.1%) got 5 marks (Excellent), 35 students (63.6%)--4 (Good) and 4 students (7.3%)--3 mark (Satisfactory). PMID- 26887139 TI - THE MORBIDITY OF UPPER AIRWAYS AND EAR IN INDUSTRIAL REGIONS OF THE REPUBLIC SAKHA (YAKUTIA). AB - The analysis of morbidity of upper airways and ear in industrial areas of the Republic Sakha (Yakutia)--Aldanskiy, Mirninskiy and Nerungrinsky regions is presented in the article. The main tendencies in dynamics of morbidity of inflammatory diseases and cancer are revealed. The reasons of increasing pathology of upper airways and ear in the studied industrial regions are defined. PMID- 26887140 TI - EXPERIMENTAL INVESTIGATION. AB - The search for the most perfect way of hollow organ obturation has been done through the history of gastro-intestinal tract surgery. lmi present time sucn aspects of the problem asmorphological changes peculiarities in the process of intestine wound repair in the zone of anastomosis and biological impermeabilty of intestine fistula, possibilities of entero entero anast6mosis different types formation are not researched enough and remain actual. PMID- 26887141 TI - SURGERY OF CONGENITAL MALFORMATIONS IN NEWBORNS. AB - The development of neonatal surgery is an important task of health care system, because birth defects have been the 2nd most prevalent cause of infant mortality for many years. In order to improve the quality of care for neonates with surgical diseases we studied the main causes of neonatal deaths during the period from 1995 to 2014, on the basis of data from the Children's Surgery Department of Yakutsk. In 77% of cases, the causes of lethal outcomes in neonates with surgical pathology were conditionally preventable. We singled out the basic organizational problems, the solution of which led to a 3.5 times reduction in mortality of infants with surgical pathology during the second period of the study (2005 2014). The main organizational aspects of the regional model of improving medical care of infants with surgical pathology are: antenatal diagnosis of malformations and prenatal consultation with children's surgeon, competent and timely transportation of newborns from district hospitals, the centralization of aid at level 3 hospitals, the introduction of modern diagnostic and treatment algorithms, methods of minimally invasive endosurgery. PMID- 26887142 TI - IMMUNOMODULATION AND TREATMENT OF ACUTE DESTRUCTIVE PANCREATITIS IN A MULTIDISCIPLINARY SURGICAL HOSPITAL. AB - This work is based on the analysis of complex treatment of 497 patients with pancreatic necrosis treated at the surgical department of the Republican Hospital No2-Center for Emergency the Republic of Sakha (Yakutia) in the period from 2010 to 2015. The study was able to adapt and improve the two-tier immunocorretion in pancreatic necrosis in a multidisciplinary surgical hospital that along with the other constituents of intensive therapy has allowed a whole to reduce the amount of intra-abdominal and extraabdominal complications--sterile pancreatic necrosis phase--from 23.6% to 14.6 and 31 6% to 15.0% respectively, total lethality--from 17.6% to 7.2% lethality in patients with non-operated group--from 15.6% to 2.2% lethality in the group of patients operated--18.4% to 10.9%. In the phase of infectious complications of pancreatic necrosis lethality rate decreased from 45.8% to 37.7%. PMID- 26887143 TI - EXPERIENCE OF TREATMENT OF CONGENITAL DIAPHRAGMATIC HERNIA AMONG BABIES. AB - The article presents our experience of treatment of congenital diaphrogmatic hernia at newborns and hernia of an esophageal opening of a diaphragm among children of early age. Since 2010 surgical tactics has been changed: the prolonged preoperative preparation with use of the device of high-frequency ventilation of lungs, correction of symptoms of pulmonary hypertensia is carried out, operation is carried out according to plan after stabilization of the patient in parameters of oxygenation and an acid-base state, operative treatment is executed by method of low-invasive endosurgery. Over the last 5 years 25 children with good functional and cosmetic results have been operated. The lethality in the case of congenital diaphragmatic hernia at newborns decreased to 12%, it was noted generally among patients with the expressed hypoplasia of lungs which died during preoperative preparation. In recent years we place emphasis on antenatal diagnosis of pathology and prenatal diagnostics of degree of a hypoplasia of a lung on indicators of a pulmonary and head index at a fetus. It wasn't noted a postoperative lethality. PMID- 26887144 TI - CLINICAL CASE OF CONDUCTING PREGNANCY AND CHILDBIRTH AT THE WOMAN WITH CHRONIC VIRAL HEPATITIS B IN THE REPLICATIVE FORM. AB - INTRODUCTION: Because of a wide circulation of the hepatitis B (HB) among persons of young age, so-called vertical transmission of a virus from mother to the child is of particular importance. Relevance of this problem of HB increases in connection with a set of ways of infection, failures are more often observed at infection by natural ways: sexual and from mother to a fetus that demands development of effective measures of prevention of transfer from mother to a fetus. AIM: To develop algorithm of maintaining pregnant women with the chronic hepatitis B (HBV) for prevention of perinatal transfer of a HBV infection in the Republic of Sakha (Yakutia) (RS (Y)). MATERIALS AND METHODS: Materials of official statistics of Territorial administration of Rospotrebnadzor of RS (Y) are studied, incidence of chronicviral hepatitises B, C and D in RS (Y) from 2003 2013 was analyzed. Clinical, laboratory and tool, serological, molecular and biological methods of research were carried out. RESULTS: The high incidence of CHV, considerable frequency of delectability of markers of a HB infection at pregnant women, feasibility of a vertical way of a transmission of infection cause interest of doctors of different specialties in this problem. In this scientific publication we analyzed an example of maintaining the pregnant woman, woman in childbirth period with chronic viral hepatitis B, with long "experience" of an illness, with existence of replication of HBV-DNA. CONCLUSIONS: To decrease the risk of perinatal transfer of a HBV infection it is recommended a quantitative PCR-research among pregnant women with HBsAg which will provide decrease in transmission frequency of HB by carrying out in need of antiviral therapy to the woman and the individualized schedule of vaccinal prevention with introduction of specific immunoglobulin to the newborn. PMID- 26887145 TI - HEALTH STATUS OF PREGNANT WOMEN. AB - The article covers the study into the structure of extragenital pathology in pregnantwomen based on the data obtained at the antenatal clinic of the perinatal center of the State Organization of the Ministry of Health of the Sakha Republic (Yakutia) National Center of Medicine - Republican Hospital No. 1 in 2013. The presence of extragenital pathology in pregnant women is a major factor in the high risk of maternal mortality. The majority of women (90%) have two or more extragenital pathologies simultaneously. In the structure of extragenital pathology in pregnant women the first most prevalent diseases are urinary system diseases, 2nd most prevalent--diseases of the cardiovascular system, 3rd most prevalent--diseases of the hematopoietic system. Diseases of the circulatory system are the leading indications for termination of pregnancy. It is necessary to increase the efficiency of cooperation between gynecologists, internists and specialists to identify women at high risk of perinatal pathology, to form prognosis in terms of carrying of pregnancy and timely decision on its prolongation and perinatal care. PMID- 26887146 TI - SURGICAL TREATMENT OF NECK AND RETROSTERNAL GOITER, CLINICAL CASE. AB - Here is a clinical case of neck and retrosternal goiter. We describe the clinical course characteristics and diagnosis of cervical-retrosternal goiter, when intrathoracic goiter was not located by palpation. PMID- 26887147 TI - DESCRIPTION OF GASTROESOPHAGEAL REFLUX DISEASE IN DIFFERENT ETHNIC GROUPS, LIVING IN THE NORTH. AB - INTRODUCTIOD: Over the past 15 years, the relative frequency of detection of erosive form of GERD has increased from 3,1 to 16%. Manifestations of GERD in different ethnic populations of Yakutia are not well understood. AIM: Studying kliniko-endoscopic and the morfofunktsionalnykh of features of GERD in various ethnic groups living in conditions of Yakutia. MATERIALS AND METHODS: The study included 168 patients with GERD of different ethnic origins. Yakuts, Evens and Evenks, were considered as indigenous people and newcomers were all persons of other nationalities, who arrived at different times from other regions of Russia. The average age was 41.75 +/- 24.73 years. RESULTS: Clinical manifestations of GERD in different ethnic groups living in Yakutia. Leukoplakia of the esophagus was detected in the indigenous population are four times more likely than newcomers. With GERD associated with thyroid disorders prevalent low level of contamination of Helicobacter pylori. Helicobacter pylori infection in patients with GERD in Yakutia was higher among immigrants than among the indigenous, with a high degree of contamination of Helicobacter pylori was detected more frequently in immigrants than among the indigenous. Pathological gastroesophageal reflux during the daily pH-metry of the esophagus was detected more frequently in patients visiting than among the indigenous. CONCLUSIONS: The found features of a current of GERD can be further the basis for the individualized and differentiated approaches to treatment of this disease. PMID- 26887148 TI - CONTRIBUTION OF CEREBRAL VASCULAR ANOMALIES IN HEMORRHAGIC STROKE STRUCTURE IN DIFFERENT RACIAL GROUPS OF YAKUTIA. AB - INTRODUCTION: Hemorrhagic stroke (HS) has higher incidence in Asian population compared to Caucasian. The reason for this phenomenon is not clearly understood. AIM: To investigate the contribution of cerebral vascular anomalies in hemorrhagic stroke structurein different racial groups of Yakutia. MATERIALS AND METHODS: The study group included 1078 consecutively hospitalized patients with acute HS. A comparative analysis of demographic data and frequency of CVA, which were identified as a cause of HS, was carried out between the group of indigenous patients of Asian race and the group of Caucasian patients. RESULTS: The proportion of hemorrhage due to rupture of cerebralarterial aneurysms (CAA) in the hospital HS structure was higher in Asians, compared to Caucasians (p = 0.001; OR = 1.7; 95% CL: 1.2-2.4). No difference in the arteriovenous malformations' (AVM) frequency was found between groups (p = 0.345), as well as in age and gender distribution (p = 0.052 and p = 0.759, respectively). The CAA frequency was higher among female patients compared to male in both racial groups (p < 0.0001; OR = 1.71; CI 95% 1.3-2.3). CONCLUSIONS: In Yakutia, the proportion of hemorrhage due to rupture of cerebral arterial aneurysmsin hemorrhagic stroke structure is higher among indigenous ethnic group of Asian race, compared to Caucasians. No difference in the arteriovenous malformations' frequency was found between racial groups, as well as in age and gender distribution. The cerebral aneurisms' frequency was higher among female patients compared to male in both racial groups. Further studies of cerebral vascular anomalies and stroke risk factors using a population-based data in different racial groups are needed. PMID- 26887149 TI - REGIONAL PECULIARITIES IN SEMEN QUALITY AND SERUM HORMONAL CONCENTRATIONS OF CITIZENS FROM YAKUTIA. AB - The objective of the present study was to evaluate sperm quality and reproductive hormonal level in an unselected population of men who were permanent residents of the Yakutsk city and compare the semen and hormonal parameters with the World Health Organization (WHO, 2001) recommended normal values and the results from other countries. A total of 145 men (mean age 24 years) agreed to be included in the study. All the volunteers completed a questionnaire, received a general and reproductive health examination by an andrologist, gave semen and blood samples. There are no differences between Yakut and Slavs in anthropometric, hormonal or sperm measures, but height and ejaculate volume were higher in Slavs than Yakut men. The data obtained indicated high frequency of suboptimal quality of sperm in males of both nations from this Siberian region in comparison with other Russian regions or European countries. PMID- 26887150 TI - [We will stick with it]. PMID- 26887151 TI - [Interrupting the vicious cycle]. PMID- 26887152 TI - [At the center of the nursing process]. PMID- 26887153 TI - [Knowledge, that works]. PMID- 26887154 TI - [A high quality of life in Swiss nursing homes]. PMID- 26887155 TI - [It depends on this]. PMID- 26887156 TI - [Slept well? Not really...]. PMID- 26887157 TI - [Strategies for improving compliance]. PMID- 26887158 TI - [Not to be confused with democracy]. PMID- 26887159 TI - [Our students want to go into nursing practice]. PMID- 26887160 TI - [Weak heart - strong person]. PMID- 26887161 TI - [To have the cake and eat it too]. PMID- 26887162 TI - [Curiosity and the desire to act]. PMID- 26887163 TI - [Student attendance: challenges and nursing impact]. PMID- 26887164 TI - [Speak, but why? And to say what to whom?]. PMID- 26887165 TI - [Prevent and ameliorate winter ailments]. PMID- 26887166 TI - [The place of independent nurses]. PMID- 26887167 TI - [The powerlessness to empower]. PMID- 26887168 TI - [Taking nursing care into all it's dimensions]. PMID- 26887169 TI - [Going on like this]. PMID- 26887170 TI - [Trial and error as sources of knowledge]. PMID- 26887172 TI - [Four writers' novels on hospital death]. PMID- 26887171 TI - [The nurse facing the decline and death of the patient]. PMID- 26887173 TI - [The mystery of the guardian angel]. PMID- 26887174 TI - [NURSING DIAGNOSES AND MIGRATION: PHENOMENOLOGICAL STUDY FROM THE IMMIGRANT'S POINT OF VIEW]. AB - OBJECTIVE: The objective of this research is to identify nursing diagnosis NANDA which is predominant within the immigrant community, linked to the migratory process and part of the framework of the Outcome Present State Test (OPT) of Pesut and Herman's critical awareness. METHODOLOGY: Keeping in mind the objectives of this research, this approaches the quality-based paradigm and follows the proposals of phenomenology research. The study was carried out using an individual semi-structured interview of 30 immigrants. A categorization of the data has been applied in accordance with the domains of NANDA for the identification of nursing diagnosis and its analysis has been carried with computer support with Atlas-ti 6.0. RESULTS: Twenty three diagnoses were identified in nine out of thirteen taxonomy NANDA domains. Analysis of their interrelationships according to the OPT model were carried out and a clinical reasoning net was created. The main diagnoses achieved in our study was: Readiness for Enhanced Coping. CONCLUSIONS: NANDA taxonomy doesn't include the migratory process in the characteristics and related factors of this nursing diagnosis. We consider that nursing taxonomy should be reassessed in order to describe more in depth the specific responses derived from the migratory experience so it can lead to a high quality health care. PMID- 26887176 TI - [BREASTFEEDING AS A METHOD OF BREAST CANCER PREVENTION]. AB - INTRODUCTION: Breast cancer is the most common type or cancer in women with an incidence of about 720,000 cases per year and a mortality between 6 and 23 per 100,000, what it means a very important global health problem. METHOD: Sistematic review in the following databases: PubMed, SciELO, Cochrane Plus, Medline, Cuiden and Embase. The search was limited to English and Spanish languages, between 2005 and 2015 and human studies. RESULTS: All studies are observational by the characteristics of the studied pathology. It is observed that there is a decreased risk of breast cancer in women who had ever breastfed compared to those who had not. This reduced risk is most evident in postmenopausal women but also happens in premenopausal. It has also been observed that protection is increased with increasing lactation duration. The protective effect of breastfeeding happens by differentiation of breast cells, by reduction of the number of ovulatory cycles and by estrogen and carcinogens excretion through human milk. CONCLUSTONS: Breastfeeding is associated with a decreased risk of breast cancer, and health teams must therefore educate mothers about its beneficial effects to themselves and their children. PMID- 26887175 TI - [NABARRA TECHNIQUE. POST-SURGICAL APPLICATION OF NOBECUTAN(r) AS BARRIER DRESSING]. AB - The incidence of neoplasia of vulva round 1-2 per 100,000 women with predominance in ranges age of diagnosis between 65-75years. This type of cancer pathology is tackled with surgical techniques summarized in simple vulvectomy or vulvectomy with unilateral or bilateral lymphadenectomy according to staging of cutaneous involvement. The morbidity of this surgical process is mainly grouped in skin moisture, dehiscence and infection. The use of Nobecutan(r) as a plastic dressing aerosol barrier reduces cutaneous surgical comorbidity. PMID- 26887177 TI - [MANAGEMENT IN THE NURSING SURGERY OF PRIMARY CARE FOR PATIENTS WITH HIGH BLOOD PRESSURE OR WITH A CARDIOVASCULAR RISK. SUGGESTION FOR THE USE OF THE APM AND SMAP]. AB - OBJECTIVE: Analyze the necessity of creating and managing a nursing surgery in Primary Care focused exclusively on the discovery, following up and derivation in the cardiovascular risk patient. METHODS: Making use of the available Scientific evidence, consider the advantages of putting into practice a system for a nurse to attend the necessities of a patient with a cardiovascular risk taking into consideration the following: 1) Estimating the risk; 2) Stratagies for nursing supervision and activities; 3) The correct registration of medical diagnosis of the patient; 4) Monitoring. RESULTS: To enable nurses to treat cardiovascular patients in Primary Care, to reduce the time the patient would have to wait to be attended and to supervise the patient's progress. CONCLUSIONS: Making it possible for nurses to use the same registered standard system for controlling the treatment of cardiovascular patients. PMID- 26887178 TI - [THE IMPORTANT ROLE OF NURSING IN ADVANCE DIRECTIVES]. AB - The advance directives' document involves patients in decisions related to their treatment; it promotes the principle of autonomy. Although advance directives' document has been regulated legally at national state and local levels, nursing professionals still have a huge lack of this issue. How they work directly with patients, it is important nurses have update knowledge to give support and information to the patients, with the aim ofproviding a quality care. PMID- 26887179 TI - [ELDERLY CAREGIVERS OF ELDERLY PEOPLE: BURDEN AND SOCIAL SUPPORT]. AB - OBJECTIVE: To determine the burden and social support perceived by elderly caregivers of elderly people. METHOD: Cross-sectional study using a standardized questionnaire for elderly caregivers of elderly people. RESULTS: In the population of elderly caregivers of elderly people, the prevalent type of care is by couples (84.1 %), and the percentages of men and women correspond to 40.2 % and 59.8 %, respectively. The 53.3 % of caregivers have burden, of which a 31.8 % present an intense burden, and a 21.5 % a slight burden. Regarding to perceived social support of elderly caregivers, it is normal in a 81.3 % of cases, compared to a 18.7 % who reflecting a low perceived social support. Finally, there is correlation between Duke social support questionnaire and Zarit scale caregiver burden. CONCLUSION: Elderly caregivers of elderly people who have higher levels of burden have lower perceived social support. PMID- 26887181 TI - A Campaign to Cut Drug Prices. PMID- 26887180 TI - [NURSING CARE TO A PATIENT WITH INTRAVESICAL TREATMENT]. AB - INTRODUCTION: Bladder cancer is one of the most frequent in developed countries. It is the 4th most frequent cancer in men and the 9th in women. The main risk factor is the smoking habit and its main symptom is hematuria. One of the therapies used in its treatment is the Bacillus Calmette-Guerin intravesical (BCG). OBJECTIVE: TO carry out a specific care plan to a patient treated with BCG and improve the information delivered to the patient and family. MATERIAL AND METHODS: An observational study of a nursing plan of care through a clinical case. A bibliographical research was carried out in the main Spanish and English databases to collect articles published in the last 5 years. Subsequently, the studies of the Spanish M.a T Luis, C. Ferndndez and M.a V. Navarro were adopted in the model suggested by V. Henderson and NANDA, NIC and NOC taxonomy. RESULTS: The nursing assessment is performed through V. Henderson's 14 needs and the Collaboration Problem was detected: Hematuria, secondary to bladder cancer and the nursing diagnosis: <>. For the planning and execution the following NOC were selected: Knowledge: management of the cancer and Knowledge: therapeutic procedure, and the NIC and its corresponding activities and their evaluation. CONCLUSION: The Nursing Care Process application with a personalised and standardised language, guarantees a quality healthcare and continuity. Moreover, it sets common targets for the nursing team. It tries to show how an appropriate control of the symptoms can be carried out at home, when the cares are taught and organised by adapting the oral or written information to each patient. PMID- 26887183 TI - SPACE Fear of the Unknown. PMID- 26887182 TI - Academia's Gender Problem. PMID- 26887184 TI - The Starfish Assassin. PMID- 26887185 TI - Divide or Conquer. PMID- 26887187 TI - Ground Control. PMID- 26887186 TI - Ballots for Bison. PMID- 26887188 TI - Branches of Science. PMID- 26887189 TI - Frictionless Finance. PMID- 26887190 TI - The Brain's Whorl. PMID- 26887192 TI - Click 'n' Pay. PMID- 26887191 TI - That Craving for Dessert. PMID- 26887194 TI - Rings of a Super Saturn. PMID- 26887193 TI - WHERE AM I? WHERE AM I GOING? PMID- 26887195 TI - DEATH IN THE WATER. PMID- 26887197 TI - The Carbon Capture fallacy. PMID- 26887196 TI - AN ON OFF SWITCH FOR GENES. PMID- 26887198 TI - DO ANIMALS KNOW WHERE BABIES COME FROM. PMID- 26887199 TI - Elegant Equations. PMID- 26887201 TI - Sleeping Beauties of Science. PMID- 26887200 TI - Murder in the Cave. PMID- 26887202 TI - [Effects of Electroacupuncture Intervention on Oxygen Free Radicals and Expression of Apoptosis-related Proteins in Rats with Ischemic Learning and Memory Disorder]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) therapy on levels of oxygen free radicals (OFR) and hippocampal apoptosis-related protein expression in ischemic learning-memory disorder rats so as to investigate its mechanisms underlying improvement of ischemic learning-memory impairment. METHODS: A total of 60 SD rats were randomly divided into sham operation (sham), model, medication, and EA groups, with 15 rats in each group. The learning-memory disorder model was made by occlusion of bilateral carotid arteries. EA (2- 3 Hz, 2 mA) was applied to "Zhi San Zhen" ["Shenting" (GV 24) and bilateral "Benshen" (GB 13)] for 30 min, once a day for 3 weeks. The rats of the medication group were treated by lavage of Aricept (0.03 mg . kg(-1) . d(-1)), once daily for 3 weeks. The rats' learning-memory ability was detected by Morris water maze tests and the state of hippocampal apoptosis cells was observed by light microscope after TUNEL staining and the expression of hippocampal Bcl-2, Bax and Caspase-3 proteins was detected by immunohistochemistry. Serum and hippocampal superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) contents were detected by chemical colorimetric analysis. RESULTS: Compared with the sham group, the escape latencies (place-navigation) after modeling were evidently prolonged, and the times of target-platform crossing in 90 sec (spatial probe test) considerably reduced in the model group (P<0.01), suggesting an impairment of learning-memory ability. After the treatment for 21 d, the increased escape latency and the reduced target-platform crossing time in both EA and medication groups were reversed in comparison with the model group (P<0.01), suggesting an improvement of memory ability, and the effect of the EA group was significantly superior to that of the medication group (P<0.05). Compared with the sham group, the number of apoptotic cells in hippocampal CA 1- CA 3 regions, and the expression levels of hippocampal Bcl-2, Bax and Caspase-3 proteins, and serum and hippocampal MDA contents were significantly increased in the model group (P<0.01), while serum and hippocampal SOD and GSH-Px levels obviously decreased in the model group (P<0.01). After the treatment for 21 days, compared to the model group, the number of the apoptotic cells, the expression levels of hippocampal Bax and Caspase--3 proteins, and the contents of serum and hippocampal MDA were notably decreased in the EA and medication groups (P<0.01), whereas, Bcl-2 protein expression levels, and serum and hippocampal SOD and GSH Px activity were notably up-regulated in the EA and medication groups (P<0.01). The effects of EA group were obviously superior to those of medication group in increasing hippocampal Bcl-2 immunoactivity, serum SOD and GSH-Px and hippocampal GSH-Px activity and in down-regulating serum MDA level (P<0.01, P<0.05). CONCLUSION: Electroacupuncture intervention can improve learning-memory ability in ischemic learning-memory disorder rats which may be associated with its effects in reducing blood and hippocampal OFR contents and hippocampal cellular apoptosis. PMID- 26887203 TI - [Effect of Electroacupuncture Stimulation of "Neiguan" (PC 6) on Expression of Myocardial Chloride Channel-related Genes, PKC and PKG Proteins in Myocardial Ischemia Rats]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6), etc. on expression levels of myocardial chloride (CL-) channel related genes and intracellular protein kinase C (PKC) protein in myocardial ischemia (M) rats. METHODS: Seventy SD rats were randomly divided into control group (n = 10), model group (n = 15) , Neiguan (PC 6) group (n = 15), Lieque (LU 7) group (n = 15) and non-acupoint group (n = 15). The MI model was established by i. p. of isoproterenol (ISO, a sympathomimetic beta adrenergic agonist). Electroacupuncture stimulation was applied to bilateral "Neiguan" (PC 6), "Lieque" (LU 7), or non-acupoint [the mid-point between "Tianshu" (ST 25) and "Shenque" (CV 8)] for 15 min, once a day for 7 days. Quantitative RT-PCR was employed to detect the expression levels of cystic fibrosis transmembrane conductance regulator (CFTR, a CL-channel) mRNA and chloride channel calcium activated 1 (CLCa 1, a member of the family of calcium-activated chloride channels, CLCa) mRNA in the left cardiac ventricle tissue, and Western blot was used to detect the expression level of myocardial PKC protein of the left ventricle. RESULTS: Compared with the control group, the expression levels of myocardial PKC protein, and CLCa 1 and CFTR genes were significantly increased in the model group (P<0.05). In comparison with the model group, the expression levels of myocardial PKC protein, and CFTR mRNA and CLCa 1 mRNA in the Neiguan group, and PKC protein and CLCa 1 mRNA in the Lieque and non-acupoint groups, as well as CFTR mRNA in the Lieque group were notably down-regulated (P<0.05). No significant change was found in the expression of CFTR mRNA in the non-acupoint group (P>0.05), and no significant differences were found between Neiguan and Lieque groups in the expression levels of PKC protein (P>0.05). The effects of "Neiguan" (PC 6) were obviously superior to those of non-acupoint in down regulating myocardial PKC protein, CLCa 1 mRNA and CFTR mRNA (P<0.05). CONCLUSION: EA stimulation of "Neiguan" (PC 6) can down-regulate the expression of myocardial PKC protein, CFTR and CLCa 1 genes in Ml rats, which may contribute to its effect in protecting rnyocardium from ischemic injury. PMID- 26887204 TI - [Effect of Acupuncture Stimulation of Different Acupoint Groups on Levels of Stress Hormones and Serum Brain-derived Neurotrophic Factor in Depression Rats]. AB - OBJECTIVE: To screen the effective acupoints for anti-depression in depression rats and to explore the mechanisms of acupuncture for relieving depression. METHODS: Fifty rats were randomly divided into normal control, model, "Yin-tang" (EX-HN 3)-"Baihui" (GV 20, 2-acupoints), EX-HN 3-GV 20-"Fengchi" (GB 20) "Shenshu" (BL 23, 4-acupoints) and medication groups, with 10 rats in each group. The depression model was established by unpredictable chronic mild stress (UCMS) for 28 days. For rats of the 2-acupoints and 4-acupoints groups, EX-HN 3 and GV 20, and EX-HN 3, GV 20, GB 20 and BL 23 were punctured with filiform needles respectively before performing mild stress every time. The acupuncture needles were retained for 30 min during each intervention and the treatment was conducted once daily for 28 days. The rats of the medication group were treated by intragastric administration of Fluoxetine (0.18 mg/kg) once a day for 28 days. The rats' anxiety-like behavior (rearing and crossing times) was detected by open field test. The contents of adrenocorticotropic hormone (ACTH) in the pituitary, 5-hydroxytryptamine (5-HT) in the hippocampus, the cortisol (CORT) in the adrenal gland, and the brain derived neurotrophic factor (BDNF) in the serum were examined by ELISA. RESULTS: Compared to the normal control group, the numbers of both rearing and crossing motions in the model group were significantly decreased (P<0.01, P<0.05), while in comparison with the model group, the rearing and crossing numbers of rats in the 2-acupoints and 4-acupoints and medication groups were significantly increased (P<0.01). ELISA showed that after modeling, the content of adrenal CORT was significantly increased (P<0.01), and those of hippocampal 5-HT and serum BDNF were obviously down-regulated in the model group (P<0.01). After the treatment, the adrenal CORT levels in the three intervention groups were notably down-regulated, and hippocampal 5-HT and serum BONE evidently up-regulated in these 3 intervention groups (P<0.05, P<0.01). No marked changes were found in the pituitary ACTH contents of the model and 3 intervention groups (P>0.05), and no significant differences were shown among the three intervention groups in the levels of the aforementioned 6 indexes (P>0.05). CONCLUSION: Acupuncture intervention can effectively improve the unprompted activates of the depression rats, which may be related to its effects in up-regulating hippocampal 5-HT and serum BONE levels, and in down-regulating adrenal CORT content. PMID- 26887205 TI - [The Expression of Substance P in Sensory Neurons and Nerve Fibers Associated with "Sanyinjiao" (SP 6) Region in the Rat]. AB - OBJECTIVE: To explore the innervation and biochemical characteristics associated with acupoint "Sanyinjiao" (SP 6) in the rat by using neural tracing and immunofluorescence techniques. METHODS: Five male SD rats were used in the present study. Alexa Fluor 488 conjugated cholera toxin subunit B (AF 488-CTB, 5 L, 1%) was injected into the site superior to the prominence of the medial malleolus, a corresponding site to acupoint SP 6 in the human body. After 3 surviving days, the rat's local tissue of SP 6 region, spinal cord and dorsal root ganglia (DRGs) at lumbar (L) segments (L 1 - S 1) were dissected following perfusion with 4% paraformaldehyde, cut into sections (20 MUm for DRG and SP 6, and 40 MUm for spinal cord) and observed under light microscope. In addition, substance P (SP) immunoreaction in the spinal cord, DRG and SP 6 region tissues was examined with immunofluorescence. RESULTS: All the labeling of AF 488-CTB appeared on the ipsilateral side of the injection. The labeled sensory and motor neurons distributed in L 3 - L 6 DRGs and spinal ventral horns with high concentration in the L 4 and L 5 segments. In addition, SP-positive neural labeling was found in small sensory neurons in DRG, axonal terminals in lamina I II of spinal dorsal horns, and free nerve fibers in local subcutaneous tissues. Additionally, 24. 1 % of AF 488-CTB labeled sensory neurons simultaneously presented a SP-positive expression. CONCLUSION: These findings reveal that the sensory and motor neurons associated with acupoint SP 6 distribute in L 3- L 6 DRGs and spinal ventral horns of rats, concentrating in the L 4 and L 5 segments, and 24.1% sensory neurons show SP-positive, suggesting a possible involvement of the primary SP-positive sensory neurons in the transmission of acupuncture stimulation signals. PMID- 26887206 TI - [Effects of Electroacupuncture Intervention Combined with Gastrodin on Expression of Proteins Related to Proliferation-differentiation of Neural Stem Cells in Hippocampal CA 1 and CA 3 Regions in Focal Cerebral Ischemia Rats]. AB - OBJECTIVE: To observe the effect of electroacupuncture(EA) combined with medication on changes of expression of Nestin, glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) in the hippocampal CA 1 and CA 3 regions of focal cerebral ischemia (FC1) rats, so as to analyze its mechanisms underlying neuroprotection. METHODS: Fifty male SD rats were randomly divided into normal control, model, EA, medication, and EA+ medication groups (n = 10 in each group). The FCI model was established by middle cerebral artery occlusion (MCAO) with thread embolus. EA (2 Hz, 2 V) was applied to the left "Hegu"(LI 4) and "Quchi" (LI 11) for 30 min, once daily for 14 days after MCAO. Rats of the medication group were given with intraperitoneal injection of gastrodin (10 mg/kg). The expression of Nestin, GFAP and NSE in the hippocampal CA 1 and CA 3 regions were detected by immunohistochemistry. RESULTS: Compared with the normal control group, the numbers of Nestin- and GFAP-immunoreaction (IR) positive cells in both CA 1 and CA 3 regions of the hippocampus were significantly increased in the model ciroup (P<0.05), while those of NSE-IR positive cells in both CA 1 and CA 3 regions were significantly decreased in the mdlgroup (P<0.05). After EA and medication interventions, the numbers of Nestin- and NSE-IR positive cells in the CA 1 and CA 3 regions were evidently increased and GFAP-IR positive neurons were considerably reduced in the EA, medication and EA+ medication groups (P<0.05). The effects of EA+ medication were significantly superior to those of both EA and simple medication in up-regulating the number of Nestin- and NSE-IR positive cells and down-regulating the number of GFAP positive neurons in CA 1 and CA 3 regions (P<0.05). CONCLUSION: EA and EA intervention combined with gastrodin can significantly up-regulate the number of Nestin- and NSE-IR positive cells, and down-regulate the number of GFAP positive cells in the CA 1 and CA 3 regions of hippocampus in focal cerebral ischemia rats, which may contribute to their effects in promoting the differentiation and proliferation of mature neurons in the hippocampus for improving cerebral functions. The effects of EA+ medication are obviously better than simple EA intervention. PMID- 26887207 TI - [Electroacupuncture Intervention Combined with Anesthetics for Analgesia and Post surgical Gastrointestinal Recovery in Pneumectomy Patients]. AB - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of bilateral Taichong (LR 3), Yan-glingquan (GB 34), Waiguan (TE 5) and Chize (LU 5) on pain and post-surgical gastrointestinal reactions in patients undergoing pneumectomy. METHODS: Sixty patients with pneumectomy were randomly divided into EA group (30 cases) and control group (30 cases). For patients of the EA group, EA stimulation (2 Hz, 3 - 5 mA) was applied to bilateral LR 3, GB 34, TE 5 and LU 5 once every 12 h in the following two days after the surgery. For patients of the control group, the filiform needles were just adhered to the abovementioned acupoints without electrical stimulation. In addition, patients of both groups were treated first with lower dose of anesthetics including Fentanyl (250 MUg) + Flurbiprofen axetil (25 mg) + normal saline (i. v., 2 mL/h), and Sauteralgyl (muscular injection if necessary). The visual analogue scale (VAS) was used for measuring the patients' pain reaction at 24(th) h and 48(th) h after surgery. The contents of plasma beta-endorphine (EP) and leu-enkephalin were assayed by ELISA, the times of vomiting and nausea, and the time of postoperative exhaust and defecation were recorded. RESULTS: Compared with the control group, the VAS score at 48 h after surgery, and the dosage of the supplemented Sauteralgyl were evidently lower, and the time of both exhaust and defecation after surgery was significantly earlier, and the degree of nausea after surgery was obviously milder in patients of the EA group (P<0.05, P<0.01). Compared with 0 h post operation, the beta-endorphin and leu-enkephalin levels were significantly increased in the EA group (P<0.01). No significant difference was found between the control and EA groups in the vomiting rating (P>0.05). CONCLUSION: EA intervention combined with anesthetics is effective in reducing the dosage of the supplemented Sauteralgyl and the degree of postoperative nausea, and in improving postoperative gastrointestinal functional recovery in patients undergoing pneumectomy. PMID- 26887209 TI - [Transcutaneous Electrical Stimulation Undergoing Emergency Treatment of Zusanli (ST 36) Is Beneficial to Rescued Organophosphorus Pesticide Poisoning Patients]. AB - OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) of Zusanli (ST 36) on gastrointestinal activities in organophosphorus pesticide poisoning (OPP) patients undergoing emergency treatment so as to explore its action in scavenging gastrointestinal toxicant. METHODS: A total of 116 OPP patients were randomly divided into control group and TAES group (n=58 in each group) according to the simple random sampling method. All the patients received comprehensive treatment including gastric lavage, catharsis, oral administration of atropine Pralidoxime Chloride, Omeprazole, etc. For patients of the TAES group, TAES stimulation (30 Hz/60 Hz, 15-20 mA) was applied to bilateral Zusanli (ST 36) for 30 min, 3 times a day till black stool was discharged. The vomiting times after catharsis, the time of the first defecation and black stool discharge, the dosage of atropine and the length of patient stay in hospital were recorded. RESULTS: Of the two 58 cases of OPP patients in the control and TAES groups, 11 (18.9%) and 3 (5.2%) underwent vomiting after catharsis, being significantly lower in the TAES group (P<0.05). Compared with the control group, the time of first defecation and black stool discharge, the dosage of the administrated atropine and the time of hospitalization were significantly lower in the TAES group (P<0.05). CONCLUSION: TAES of ST 36 may lower incidence of emesis, enhance the cathartic effect, promote gastrointestinal poison discharge, reduce total atropine dosage and shorten the hospitalization time in OPP patients, favoring the patient's rehabilitation. PMID- 26887208 TI - [Different Warm Sensations May Induce Different Therapeutic Effects in Primary Dysmenorrhea Patients Undergoing Moxibustion Treatment Based on Propensity Score: A Prospective Cohort Study]. AB - OBJECTIVE: To compare the effectiveness difference between the "heat-sensitive" sensation and conventional warm sensation of moxibustion stimulation of Guanyuan (GV 4) in primary dysmenorrhea (PD) patients. METHODS: Cohort study design was used in the present study. A total of 189 PD patients were divided into heat sensitive group (n = 148) and conventional warm sensation group (n = 41) according to the patients' subjective feeling to moxibustion stimulation and the sequence of treatment. The Propensity Score Match (PSM)function of SPSS 19.0 software was used to match the patients of the two groups for balancing their baseline data (age, duration of illness, McGill and CMSS scores). Thus, 35 cases in each group were subjected into the analysis at last. Heat-sensitive moxibustion was applied to Guanyuan (GV 4) for 40 min beginning 5 days before dysmenorrheal attack, once daily for (7 +/- 2) days in one menstrual cycle, and for 3 menstrual cycles for heat-sensitive group, wheras routine moxibustion for conventional warm sensation group. The McGill Pain Questionnaire (MPQ) composed of pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI) and COX Menstrual Symptom Scale (CMSS) containing 18 items (0 - 4 grades/item) were used to evaluate the therapeutic effect of moxibustion treatment. Follow-up visit was conducted 3 months after the treatment. RESULTS: Compared to pre-treatment, MPQ and CMSS scores were significantly decreased in both groups after the treatment (P<0.01), and the effects of heat-sensitive group were significantly superior to those of conventional warm sensation group in lowering MPQ and CMSS scores (P<0.01). Follow-up survey showed that both MPQ and CMSS scores were still considerably lower in the heat-sensitive group than in the conventional warm sensation group (P<0.01, P<0.05). CONCLUSION: The heat sensitive moxibustion is superior to conventional warm moxibustion in improving symptoms in primary dysmenorrhea patients. PMID- 26887210 TI - [Effects of Acupuncture Intervention Combined with Rehabilitation on Standing balance-walking Ability in Stroke Patients]. AB - OBJECTIVE: To observe the influence of acupuncture stimulation of lateral side of Tianzhu (para-BL 10), electroacupuncture (EA) stimulation of scalp-point Balance Area (MS 14), Motor Area (MS 6) and body acupoints combined with rehabilitation training on standing-balance and walking ability in stroke patients. METHODS: A total of 145 stroke inpatients were randomly assigned to rehabilitation group (n=48), routine acupuncture group (n=49) and para-BL10 group (n = 48). Patients of the rehabilitation group received balance training and routine rehabilitation training treatment, those of the routine acupuncture group received acupuncture stimulation of scalp-points (MS 14, MS 6), body acupoints, balance training and routine rehabilitation training,and those of the para-BL10 group received acupuncture stimulation of lateral side of BL 10 combined with scalp-points of MS 14 and MS 6 and body acupoints, and balance training and routine rehabilitation training. The treatment was conducted once daily, 5 times per week, 8 weeks altogether. The patients' balancing function, lower-limb motor function and walking ability were assessed using Berg Balance Scale (BBS), Sheikh Trunk Control Ability Scale(STCAS), Fugl-Meyer Assessment Scale (FMAS), and Holden Functional Ambulation Classification (FAC), respectively. RESULTS: After 4 and 8 weeks' treatment, the scores of BBS, STCAS, FMAS and FAC in patients of the rehabilitation, routine acupuncture and para-BL10 groups were significantly increased and 10 meters-walking time obviously reduced in comparison with pre treatment in the same one group (P<0.01). The effects of acupuncture stimulation of para-BL 10 were considerably better than both rehabilitation and routine acupuncture groups in raising BBS, STCAS, FMAS and FAC scores and in reducing 10 m-walking time (P<0.05). CONCLUSION: Acupuncture stimulation of lateral side of BL 10 combined with scalp-points has a significant benefit for stroke patients in standing-balance ability and walking ability. PMID- 26887212 TI - [Effect of Acupuncture Therapy on Visceral Fat Thickness in Simple Central Obesity Patients]. AB - OBJECTIVE: To evaluate the efficacy of acupuncture therapy in decreasing visceral fat thickness(VFT) in patients with simple central obesity. METHODS: Sixty patients with simple central obesity (syndrome of stomach and intestinal excessive heat) were randomly divided into control and acupuncture groups. Patients of the control group were treated with diet control and physical exercise procedure (basic treatment) for 6 months, and those of the acupuncture group treated with basic treatment combined with acupuncture stimulation of main acupoints Shuifen (CV 9), Yinjiao (CV 7), and bilateral Tianshu (ST 25), Huaroumen (ST 24) and bilateral Wailing (ST 26), etc., in combination with electroacupuncture (EA, 50- 100 Hz, 1- 5 mA) of bilateral ST 25, CV 9 and CV 7 for 30 min, once every other day for 3 months. The VFT (1 cm above the umbilicus) was detected by using an ultrasonic diagnosis instrument, and the body mass index (BMI, body weight/height(2)), and waist circumfe-rence (WC) were measured before treatment, 3 and 6 months after the treatment, respectively. RESULTS: Following 3 and 6 months' treatment, the VFT, BMI and WC of both groups were significantly decreased (P<0.01), and the effects of the acupuncture group were significantly superior to those of the control group in lowering VFT [(51.5 +/- 6.5) mm vs (48.3 +/- 4.7) mm)] and WC [(88.2 +/- 3.6)cm vs (85.9 +/- 4.3)cm] 6 months' after the treatment (P<0.05). There was no significant difference between the control and acupuncture groups in BMI fowllowing 6 months' treatment [(31.0 +/- 4.3) vs (30.1 +/- 3.2), P>0.05]. CONCLUSION: Acupuncture intervention combined with diet control and physical exercise can effectively decrease VFT and WC in simple central obesity patients. VFT is a sensitive and better parameter for evaluating the effect of obesity treatment. PMID- 26887211 TI - [Acupuncture Stimulation of Acupoints of Multiple Meridians for Patients with Diminished Ovarian Reserve of Both Yin and Yang Deficiency]. AB - OBJECTIVE: To observe the effect of acupuncture stimulation of acupoints of the Conception Vessel, Kidney Meridian, Spleen Meridian, and Bladder Meridian on menstrual cycles and duration, and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estrogen 2 (E(2)) levels in patients with diminished ovarian reserve (DOR). METHODS: A total of 96 patients with DOR of both yin and yang deficiency were randomly divided into medication group and acupuncture group (n = 48 cases in each group). Patients of the medication group were treated by Estradiol Valerate tablets, 2 mg/d on the first 10 days, and Estradiol Cyproterone, 3 mg/d from day 11 to 21, followed by 5 -7 days' rest, and the next therapeutic course, continuously for 6 months. For patients of the acupuncture group, filiform acupuncture needles were separately inserted into every 5 points of the Conceptional Vessel, Kidney, Spleen and Bladder Meridians, manipulated with uniform reinforcing and reducing methods till Deqi, and retained for 40 min. The treatment was conducted once daily for consecutive 10 days in one menstrual cycle, beginning from the 10(th) day on after menstruation, which was repeated for 6 months. The integrative scores (normal = 0, mild=2, moderate=4 and severe=6 points) of menstrual cycle, menstrual duration, amount, color, quality [blood blot or ame- nia, symptoms of traditional Chinese medicine (TCM)] were assessed according to "Guiding Principles for Clinical Trials of New Drugs of Chinese Materia Medica". Serum FSH, LH and E(2) contents were detected by Roche's electrochemical luminescence method. RESULTS: After the treatment, of the two 48 cases in the medication and acupuncture groups, 12 (25.0%) and 20 (4.7) were cured, 11 (22.9 %) and 12 (25.0 %) experienced marked improvement in their symptoms, 20 (41.7%) and 10 (20.8%) were effective, and 5 (10.4%) and 6 (12.5%) failed, with the effective rate being 89.6% and 87.5%, respectively. The integral score of TOM symptoms, menstrual cycle, serum FSH, LH and E2 contents were considerably diminished in both groups after 6 months of treatment (P<0.05), and the TOM symptom score, menstrual cycle, and serum FSH, LH and E2 levels were significantly lower in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05), while the menstrual duration in each cycle was notably longer in both groups after the treatment, and evidently longer in the acupuncture group than in the medication group 6 months after cease of the treatment (P<0.05). No significant differences were found between the two groups in the effective rate, score of TOM symptoms, menstrual cycle and duration, and serum FSH, LH and E(2) contents following the treatment (P>0.05). CONCLUSION: Acupuncture stimulation of acupoints of the Conception Vessel, Kidney, Spleen, and Bladder Meridians is effective in improving clinical symptoms of DOR patients with deficiency of both yin and yang, and has a longer effect, which may be closely associated with its functions in lowering serum FSH, LH and E(2) levels through regulating the hypothalamic-pituitary-ovarian axis. PMID- 26887213 TI - [Effect of Electroacupuncture Intervention on Rehabilitation of Upper Limb Motor Function in Patients with Ischemic Stroke]. AB - OBJECTIVE: To observe the effect of electro-elongated needle intervention on rehabilitation of upper limb motor function in patients with ischemic stroke. METHODS: A total of 100 ischemic stroke patients were equally and randomly divided into manual acupuncture group and electro-elongated needle group (n=50 cases/group). For patients of the manual acupuncture group, filiform needles were respectively inserted into Jianyu (LI 15), Jiquan (HT 1), Shousanli (LI 10), Neiguan (PC 6) and Hegu (LI 4) on the affected side, manipulated with lifting thrusting reinforcing or reducing method for 40 min, once daily for two weeks except the weekends, and for those of the electro-elongated needle group, elongated needles were repeatedly penetrated from LI 15 to Binao (LI 14), and from LI 10 to Waiguan (TE 5) on the affected side, followed by electrical stimulation for 40 min, once daily for two weeks except weekends. The therapeutic effect of manual acupuncture and electro-elongated needle for upper extremity rehabilitation was assessed according to the modified upper-extremity Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) separately. The surface electromyogram (sEMG) of the deltoid muscle was recorded by using a Megawin Surface Electrogram System and the root mean square (RMS) of the amplitude of sEMG was used to evaluate the functional state of the deltoid muscle. RESULTS: After the treatment, the score of FMA and WMFT in both manual acupuncture and electro-elongated needle groups were significantly increased compared with pre treatment in the same one group (P<0.01), suggesting an improvement of the motor function of the upper limbs, but RMS ratios of the amplitude of sEMG were evidently decreased in both groups (P<0.05, P<0.01), suggesting a relief of the abnormal muscular tension. The therapeutic effects of the electro-elongated needle were obviously superior to those of manual acupuncture in up-regulating FMA and WMFT scores and down-regulating RMS ratio (P<0.01). CONCLUSION: Electro elongated needle therapy can effectively improve the motor function of upper limb in ischemic stroke patients and has a better effect in comparison with simple manual acupuncture. PMID- 26887214 TI - [Clinical Trials of Triple-puncture Stimulation of Zhibian (BL 54), ctc. plus Moxibustion for Benign Prostatic Hyperplasia]. AB - OBJECTIVE: To observe the clinical efficacy of triple-puncture stimulation of Zhibian (BL 54), etc. combined with moxibustion therapy for patients with benign prostatic hyperplasia (BPH). METHODS: Two hundred patients with BPH who met the inclusive criteria were randomized into control (acupuncture) and treatment (acupuncture plus moxibustion) groups (n = 100 cases in each one). Patients of both the control and treatment groups were treated by puncturing the sensitive spot of bilateral Zhibian (BL 54, with triple filiform needles), and other main acupoints as Pang-Shuidao (ST 28, one cun beside ST 28), Pang-Guilai (ST 29, one cun beside ST 29), Shenshu (BL 23), Sanyinjiao (SP 6), Guanyuan (CV 4), Zhongji (GV 7), and some supplemented acupoints selected according to the syndrome identification. In addition, for patients of the treatment group, bird-pecking moxibustion was applied to bilateral Zhibian (BL 54), and the rest acupoints were punctured with filiform needles which were attached with ignited moxa stick segments. The treatment was conducted for 30 min every time, once every day for 20 times, with 2 days' rest between the two 10 days' treatments. The state of the patients' prostate (micturation state) was evaluated according to the "International prostate symptom score" (I-PSS, 0 - 35 poins, 7 symptom questions) and quality of life (QOL, 0 - 6 points) score before and after the treatment. RESULTS: After the treatment, both l-PSS score and QOL score of the two groups were significantly decreased compared with pre-treatment in the same one group (P<0.01), and the effect of the treatment group was evidently superior to that of the control group in lowering I-PSS score and QOL score (P<0.01). Of the two 100 cases in the control and treatment groups, 23 (23.0%) and 42(42.0%) experienced a marked improvement, 51(51.0%) and 47 (47.0%) were effective, and 26 (26.0%) and 11(11.0%) invalid, with the effective rates being 74.0% and 89.0%, respectively. The therapeutic effect of the treatment group was obviously superior to that of the control group (P<0.01). CONCLUSION: Acupuncture plus moxibustion treatment is effective in improving BPH patients' micturation symptoms, which is superior to the simple acupuncture intervention. PMID- 26887215 TI - [Basic Characteristics of Simplex Reinforcing and Reducing Manipulations of Filiform Acupuncture Needle in Clinical Practice Based upon Data Mining]. AB - OBJECTIVE: To explore the regularities and features of clinical application of simplex reinforcing or reducing manipulation of filiform acupuncture needles by data mining in order to guide clinical decision in a better way. METHODS: A database about simplex reinforcing and reducing manipulations of filiform acupuncture needle was established first after collection, sorting, screening, type-in, and collation of the related papers, academic dissertations and theses of academic conferences published from January 1st of 1950 to January 31 of 2015 by using key word "acupuncture" "acupuncture and moxibustion" "needle manipulation" and "filiform needle" from database of China National Knowledge Infrastructure (CNKI, a full-text database of Chinese journals), followed by data extraction and statistical analysis. RESULTS: A total of 1 304 articles were found to meet the standards formulated in the present study. Among them, 800 papers belong to the internal medicine covering apoplectic sequelae (153 papers), apoplexy (52), headache (63) and insomnia (60), 271 to surgery involving soft tissue injury (63) and backleg pain (46); 93 to five-sense-organs involving nasosinusitis (14), 64 gynecology involving dysmenorrhea (13), 41 to dematology involving struma (20), and 35 to pediatrics covering five kinds of tardy growth and five flaccid syndromes(8). These 1 304 papers contain 2 542 of simplex reinforcing and reducing manipulations, including 895 of twirling-thrusting reducing, 611 of twirling-rotating reinforcing, 571 of lifting-thrusting reducing, 303 of lifting-thrusting reinforcing, 32 of reinforcing and 32 of reducing in cooperation wihpatients' respiration, 23 open-close reducing, 12 open close reinforcing, 21 reducing and 16 of reinforcing achieved by inserting the needle along or against the meridian, 14 rapid-slow reinforcing, and 12 rapid slow reducing. Regarding the acupoint selection, distal and local acupoints are most frequently used, followed by symptoms-determined and syndrome-determined, respectively. The acupuncture needle retained time was from 0 min to 45 mn, and the therapeutic effect was relatively better for post-stroke. The totally therapeutic effects of the simplex reinforcing and reducing manipulations were 96.07% for problems of demotology, 94.19% for gynecology, 96. 58% for surgery, 92.85% for pediatrics, 91.78% for five-sense organs and 93. 70% for internal medicine, respectively. CONCLUSION: Simplex reinforcing and reducing manipulations of acupuncture has a definite effect in the treatment of different problems particularly in the internal medicine and surgery. Often, the twirling rotating and lifting-thrusting reinforcing and reducing manipulations of acupuncture are employed in clinical practice. PMID- 26887216 TI - [From Biological Effects of Local Cutaneous Thermal Stimulation to Moxibustion Therapy]. AB - Moxibustion is one of the major external therapies of traditional Chinese medicine (TCM) and exerts a definite favorable effect in the treatment of patients with different problems. In the present paper, the authors reviewed 38 papers about somatic thermal intervention therapy published in recent 15 years and analyzed its biological functions from local, distal, and whole body effects. The local effects include 1) improving cutaneous inflammatory illnesses as verruca, herpes simplex, Leishmania infection, cutaneous necrosis, wound disunion, and promoting percutaneous absorption of some medicines, swelling pain; 2) reliving sports fatigue and muscular injury, eliminating inflammation and pain reactions, probably by lowering local reactive oxygen species, superoxide dismutase,catalase, glutathione, etc. levels, and strengthening the flexibility of the knee-joint, and anterior and posterior cruciate ligaments; 3) increasing blood perfusion of the regional arteriola, micrangium to eliminate accumulated subcutaneous blood cells, inflammatory mediators and other metabolic products. The distal effects contain 1) increase of the distal cutaneous blood flow and suppression of the arterial stenosis; and 2) improvement of the visceral functions including the heart (ischemia), liver, gastrointestinal blood flow and smooth muscles, uterus smooth muscular tension, etc. The whole body effects include raising immunoability against cancer, and reducing tumor blood flow to damage the blood vessels in the tumor tissue, etc. In addition, the effects of thermal stimulation are affected by the temperature, stimulating duration and the stimulated positions. These research results may help us to comprehensively understand the effects and mechanisms of moxibustion therapy in the treatment of different clinical disorders. PMID- 26887217 TI - [Acupuncture Intervention Reduced Weight Gain Induced by Hypoglycemic Agents through Food Intake-related Targets in Central Nervous System]. AB - Clinical practice shows that thiazolidinediones (TZDs) induce weight gain in patients with type-II diabetes mellitus during treatment, which restrains its application and generalization clinically. It has been demonstrated that acupuncture therapy is useful in easing obesity in clinical trials. In the present paper, we summarize the underlying mechanism of weight gain induced by TZDs through food intake-related targets in the central nervous system and analyze the possible effects of acupuncture therapy. Acupuncture therapy is expected to reduce weight gain side effect of TZDs through 1) lowering permeability of blood brain barrier to reduce TZDs concentration in the brain, 2) upregulating the expression of hypothalamic leptin and inhibiting hypothalamic neuropiptide Y expression, and 3) down-regulating activities of peroxisome proliferator-activated receptor to reduce energy intake and fat syntheses. PMID- 26887218 TI - Serum Uric Acid and Mortality Form Cardiovascular Disease: EPOCH-JAPAN Study. AB - AIM: To investigate the relationship between serum uric acid levels and cardiovascular disease in Asians. METHODS: We examined the above relationship using the data of Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN Study). The data of 36,313 subjects (15,628 men and 20,685 women aged 35-89 years without histories of stroke, coronary heart disease, or cancer at baseline) were used for the analyses. Sex-specific hazard ratios (HRs) of mortality from cardiovascular disease were estimated according to the quintiles of serum uric acid using Cox hazard models stratified by cohorts. RESULTS: During 441,771 person-years of follow-up, we documented 1,288 cardiovascular deaths. A J- or U-shaped relationship between serum uric acid level and cardiovascular disease mortality was observed. Compared with the lowest quintile of serum uric acid levels, the highest quintile was associated with an increased cardiovascular disease mortality in men [HR: 1.28; 95% confidence interval (CI): 1.01-1.63] and women (HR: 1.51; 95% CI: 1.14-1.99). However, there was no significant association with mortality from stroke, coronary heart disease or heart failure in both men and women. CONCLUSION: This large pooled analysis in Japan suggested a J- or U-shaped relationship between serum uric acid levels and cardiovascular mortality. The highest quintile of serum uric acid levels was associated with increased cardiovascular disease mortality in both Japanese men and women. PMID- 26887219 TI - Predictors of Carotid Intima-Media Thickness and Plaque Progression in a Chinese Population. AB - AIM: Atherosclerotic diseases are the leading cause of death worldwide. Longitudinal changes in carotid intima-media thickness (IMT) and plaque are being increasingly used as markers of atherosclerosis progression and may predict future cardiovascular events. This study aimed to investigate the predictors of carotid IMT and plaque progression in a Chinese population and to determine whether these predictors differ by gender. METHODS: Segment-specific carotid IMT and plaque were measured in 712 stroke- and myocardial infarction-free subjects at baseline and after an average interval of 4.3+/-0.9 years. Multivariate linear regression and logistic regression analyses were conducted to investigate the predictive effect of age, gender, and cardiovascular risk factors on carotid IMT and plaque progression. Gender-specific analyses were also performed. RESULTS: Overall, age and smoking were predictors of common carotid artery IMT progression (adjusted p<0.001 and p=0.045, respectively). Age, hypertension, and use of antihypertensive medication were predictors of bifurcation IMT progression (adjusted p<0.001, p=0.033, and p<0.001, respectively). The use of antihypertensive medication was associated with less annual IMT progression in hypertensive subjects than in those who did not take medication, which was most prominent in the bifurcation segment. In addition, most predictors of IMT progression were identified in women in a gender-specific analysis. For plaque progression, age and gender were independent predictors. CONCLUSIONS: The predictors of carotid atherosclerosis progression were gender and segment specific. The detection and control of hypertension may prevent atherosclerosis progression, particularly in women. PMID- 26887220 TI - Bacterial treatment of alkaline cement kiln dust using Bacillus halodurans strain KG1. AB - This study was conducted to isolate an acid-producing, alkaliphilic bacterium to reduce the alkalinity of cement industry waste (cement kiln dust). Gram-positive isolate KG1 grew well at pH values of 6-12, temperatures of 28-50 degrees C, and NaCl concentrations of 0-16% and thus was further screened for its potential to reduce the pH of an alkaline medium. Phenotypic characteristics of the KG1 isolate were consistent with those of the genus Bacillus, and the highest level of 16S rRNA gene sequence similarity was found with Bacillus halodurans strain DSM 497 (94.7%). On the basis of its phenotypic characteristics and genotypic distinctiveness from other phylogenetic neighbors belonging to alkaliphilic Bacillus species, the isolated strain was designated B. halodurans strain KG1, with GenBank accession number JQ307184 (= NCIM 5439). Isolate KG1 reduced the alkalinity (by 83.64%) and the chloride content (by 86.96%) of cement kiln dust and showed a potential to be used in the cement industry for a variety of applications. PMID- 26887221 TI - The improvement of competitive saprophytic capabilities of Trichoderma species through the use of chemical mutagens. AB - The antagonistic potential of Trichoderma strains was assayed by studying the effect of their culture filtrate on the radial growth of Sclerotium rolfsii, the causal agent of chickpea collar rot. Trichoderma harzianum-1432 (42.2%) and Trichoderma atroviride (40.3%) were found to be strong antagonists. To enhance their antagonistic potential, mutagenesis of these two selected strains was performed. Two mutants, Th-m1 and T. atroviride m1, were found to be more effective than their parent strains. The enzymatic activities of the selected parent and mutant strains were assayed, and although both mutants were found to have enhanced enzymatic activities compared to their respective parent strains, Th-m1 possessed the maximum cellulase (5.69U/mL) and beta-1,3-glucanase activity (61.9U/mL). Th-m1 also showed high competitive saprophytic ability (CSA) among all of the selected parent and mutant strains, and during field experiments, Th m1 was found to successfully possess enhanced disease control (82.9%). PMID- 26887222 TI - Isolation and characterization of phenol degrading yeasts from wastewater in the coking plant of Zarand, Kerman. AB - Phenol and phenolic compounds are environmental pollutants present in industrial wastewaters such as coal tar, oil refineries and petrochemical plants. Phenol removal from industrial effluents is extremely important for the protection of environment. Usually, phenol degradation is carried out by physicochemical methods that are costly and produce hazardous metabolites. Recently, phenol biodegradation has been considered. Yeasts are the most important phenol biodegraders. In this study, the phenol-degrading yeast from environmental samples (soil and wastewater) was isolated from the coking plant of Zarand, Kerman. Then total heterotrophic yeasts were counted. The soil samples had higher rates of yeast degrader, in comparison to wastewater samples. After three passages, four yeasts (K1, K2, K7 and K11) that had the highest growth rate were selected for further study. Also, these yeasts were able to remove phenol measured by Gibbs reagent. The effect of four different concentrations of phenol (50, 125, 200 and 275) mgL(-1) was measured and three degradation patterns in these yeasts were observed. The hydrophobicity and emulsification activity were measured in all eleven yeasts. Finally, strong yeasts in phenol degrading yeasts were identified by molecular method using amplification of 18S rRNA gene region. The sequencing results showed that these isolated yeasts belonged to Candida tropicalis strain K1, Pichia guilliermondii strain K2, Meyerozyma guilliermondii strain K7 and C. tropicalis strain K11. PMID- 26887223 TI - Cultural conditions on the production of extracellular enzymes by Trichoderma isolates from tobacco rhizosphere. AB - Twelve isolates of Trichoderma spp. isolated from tobacco rhizosphere were evaluated for their ability to produce chitinase and beta-1,3-glucanase extracellular hydrolytic enzymes. Isolates ThJt1 and TvHt2, out of 12 isolates, produced maximum activities of chitinase and beta-1,3-glucanase, respectively. In vitro production of chitinase and beta-1,3-glucanase by isolates ThJt1 and TvHt2 was tested under different cultural conditions. The enzyme activities were significantly influenced by acidic pH and the optimum temperature was 30 degrees C. The chitin and cell walls of Sclerotium rolfsii, as carbon sources, supported the maximum and significantly higher chitinase activity by both isolates. The chitinase activity of isolate ThJt1 was suppressed significantly by fructose (80.28%), followed by glucose (77.42%), whereas the beta-1,3-glucanase activity of ThJt1 and both enzymes of isolate TvHt2 were significantly suppressed by fructose, followed by sucrose. Ammonium nitrate as nitrogen source supported the maximum activity of chitinase in both isolates, whereas urea was a poor nitrogen source. Production of both enzymes by the isolates was significantly influenced by the cultural conditions. Thus, the isolates ThJt1 and TvHt2 showed higher levels of chitinase and beta-1,3-glucanase activities and were capable of hydrolyzing the mycelium of S. rolfsii infecting tobacco. These organisms can be used therefore for assessment of their synergism in biomass production and biocontrol efficacy and for their field biocontrol ability against S. rolfsii and Pythium aphanidermatum infecting tobacco. PMID- 26887224 TI - Azole resistance in Candida spp. isolated from Catu Lake, Ceara, Brazil: an efflux-pump-mediated mechanism. AB - Since, there is no study reporting the mechanism of azole resistance among yeasts isolated from aquatic environments; the present study aims to investigate the occurrence of antifungal resistance among yeasts isolated from an aquatic environment, and assess the efflux-pump activity of the azole-resistant strains to better understand the mechanism of resistance for this group of drugs. For this purpose, monthly water and sediment samples were collected from Catu Lake, Ceara, Brazil, from March 2011 to February 2012. The obtained yeasts were identified based on morphological and biochemical characteristics. Of the 46 isolates, 37 were Candida spp., 4 were Trichosporon asahii, 3 were Cryptococcus laurentii, 1 Rhodotorula mucilaginosa, and 1 was Kodamaea ohmeri. These isolates were subjected to broth microdilution assay with amphotericin B, itraconazole, and fluconazole, according to the methodology standardized by the Clinical and Laboratory Standards Institute (CLSI). The minimum inhibitory concentrations (MICs) of amphotericin B, itraconazole, and fluconazole were 0.03125-2MUg/mL, 0.0625 to >=16MUg/mL, and 0.5 to >=64MUg/mL, respectively, and 13 resistant azole resistant Candida isolates were detected. A reduction in the azole MICs leading to the phenotypical reversal of the azole resistance was observed upon addition of efflux-pump inhibitors. These findings suggest that the azole resistance among environmental Candida spp. is most likely associated with the overexpression of efflux-pumps. PMID- 26887225 TI - Decolorization of azo dyes (Direct Blue 151 and Direct Red 31) by moderately alkaliphilic bacterial consortium. AB - Removal of synthetic dyes is one of the main challenges before releasing the wastes discharged by textile industries. Biodegradation of azo dyes by alkaliphilic bacterial consortium is one of the environmental-friendly methods used for the removal of dyes from textile effluents. Hence, this study presents isolation of a bacterial consortium from soil samples of saline environment and its use for the decolorization of azo dyes, Direct Blue 151 (DB 151) and Direct Red 31 (DR 31). The decolorization of azo dyes was studied at various concentrations (100-300mg/L). The bacterial consortium, when subjected to an application of 200mg/L of the dyes, decolorized DB 151 and DR 31 by 97.57% and 95.25% respectively, within 5 days. The growth of the bacterial consortium was optimized with pH, temperature, and carbon and nitrogen sources; and decolorization of azo dyes was analyzed. In this study, the decolorization efficiency of mixed dyes was improved with yeast extract and sucrose, which were used as nitrogen and carbon sources, respectively. Such an alkaliphilic bacterial consortium can be used in the removal of azo dyes from contaminated saline environment. PMID- 26887226 TI - Fusarium culmorum affects expression of biofilm formation key genes in Bacillus subtilis. AB - It is known that there is correlation between biofilm formation and antagonistic activities of Bacillus subtilis strains; but, the mechanism of this correlation is not clear. So, the effect of the plant pathogen (Fusarium culmorum) on the biofilm formation in a B. subtilis strain with high antagonistic and biofilm formation activities was studied. The expression of sinR and tasA genes involved in the biofilm formation was studied in both single culture of bacterium (B) and co-culture with F. culmorum (FB) using real-time PCR. The results revealed that the expression of the sinR gene in both B and FB conditions was continuously decreased during the biofilm formation period and, after 24h (B4 and FB4), it reached 1% and 0.3% at the planktonic phase (B1), respectively, whereas the expression of the tasA was continuously increased and was 5.27 and 30 times more than that at the planktonic phase (B1) after 24h, respectively. So, the expression reduction rate for sinR (3 times) and the expression increasing rate for tasA (6 times) were significantly higher in FB conditions than the B ones. The relative expression of sinR in FB1 (planktonic phase), FB2 (8h), FB3(12h), and FB4 (24h) times was 0.65, 0.44, 0.35, and 0.29, whereas the tasA gene expression was 2.98, 3.44, 4.37, and 5.63-fold of the one at coordinate time points in B conditions, respectively. The significant expression reduction of sinR and increase of tasA confirmed that the presence of pathogen could stimulate biofilm formation in the antagonistic bacterium. PMID- 26887227 TI - Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India. AB - Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several Pseudomonas and Klebsiella species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (merP and merT) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the merP gene showed 86-99% homology, while the merT gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment. PMID- 26887228 TI - Comparing how land use change impacts soil microbial catabolic respiration in Southwestern Amazon. AB - Land use changes strongly impact soil functions, particularly microbial biomass diversity and activity. We hypothesized that the catabolic respiration response of the microbial biomass would differ depending on land use and that these differences would be consistent at the landscape scale. In the present study, we analyzed the catabolic response profile of the soil microbial biomass through substrate-induced respiration in different land uses over a wide geographical range in Mato Grosso and Rondonia state (Southwest Amazon region). We analyzed the differences among native areas, pastures and crop areas and within each land use and examined only native areas (Forest, Dense Cerrado and Cerrado), pastures (Nominal, Degraded and Improved) and crop areas (Perennial, No-Tillage, Conventional Tillage). The metabolic profile of the microbial biomass was accessed using substrate-induced respiration. Pasture soils showed significant responses to amino acids and carboxylic acids, whereas native areas showed higher responses to malonic acid, malic acid and succinic acid. Within each land use category, the catabolic responses showed similar patterns in both large general comparisons (native area, pasture and crop areas) and more specific comparisons (biomes, pastures and crop types). The results showed that the catabolic responses of the microbial biomass are highly correlated with land use, independent of soil type or climate. The substrate induced respiration approach is useful to discriminate microbial communities, even on a large scale. PMID- 26887229 TI - Bacterial ecology of abattoir wastewater treated by an anaerobic digestor. AB - Wastewater from an anaerobic treatment plant at a slaughterhouse was analysed to determine the bacterial biodiversity present. Molecular analysis of the anaerobic sludge obtained from the treatment plant showed significant diversity, as 27 different phyla were identified. Firmicutes, Proteobacteria, Bacteroidetes, Thermotogae, Euryarchaeota (methanogens), and msbl6 (candidate division) were the dominant phyla of the anaerobic treatment plant and represented 21.7%, 18.5%, 11.5%, 9.4%, 8.9%, and 8.8% of the total bacteria identified, respectively. The dominant bacteria isolated were Clostridium, Bacteroides, Desulfobulbus, Desulfomicrobium, Desulfovibrio and Desulfotomaculum. Our results revealed the presence of new species, genera and families of microorganisms. The most interesting strains were characterised. Three new bacteria involved in anaerobic digestion of abattoir wastewater were published. PMID- 26887230 TI - Exploring plant growth-promotion actinomycetes from vermicompost and rhizosphere soil for yield enhancement in chickpea. AB - The main objective of the present study was to isolate and characterize actinomycetes for their plant growth-promotion in chickpea. A total of 89 actinomycetes were screened for their antagonism against fungal pathogens of chickpea by dual culture and metabolite production assays. Four most promising actinomycetes were evaluated for their physiological and plant growth-promotion properties under in vitro and in vivo conditions. All the isolates exhibited good growth at temperatures from 20 degrees C to 40 degrees C, pH range of 7-11 and NaCl concentrations up to 8%. These were also found highly tolerant to Bavistin, slightly tolerant to Thiram and Captan (except VAI-7 and VAI-40) but susceptible to Benlate and Ridomil at field application levels and were found to produce siderophore, cellulase, lipase, protease, chitinase (except VAI-40), hydrocyanic acid (except VAI-7 and VAI-40), indole acetic acid and beta-1,3-glucanase. When the four actinomycetes were evaluated for their plant growth-promotion properties under field conditions on chickpea, all exhibited increase in nodule number, shoot weight and yield. The actinomycetes treated plots enhanced total N, available P and organic C over the un-inoculated control. The scanning electron microscope studies exhibited extensive colonization by actinomycetes on the root surface of chickpea. The expression profiles for indole acetic acid, siderophore and beta-1,3-glucanase genes exhibited up-regulation for all three traits and in all four isolates. The actinomycetes were identified as Streptomyces but different species in the 16S rDNA analysis. It was concluded that the selected actinomycetes have good plant growth-promotion and biocontrol potentials on chickpea. PMID- 26887231 TI - Alternariol 9-methyl ether from the endophytic fungus Alternaria sp. Samif01 and its bioactivities. AB - One bioactive compound, identified as alternariol 9-methyl ether, was isolated from the crude extract of the endophytic fungus Alternaria sp. Samif01 residing in the roots of Salvia miltiorrhiza Bunge. Alternariol 9-methyl ether was active against bacteria with minimum inhibitory concentration values ranging from 25 to 75MUg/mL and median inhibitory concentration (IC50) values ranging from 16.00 to 38.27MUg/mL. The IC50 value of alternariol 9-methyl ether against spore germination of Magnaporthe oryzae was 87.18MUg/mL. Alternariol 9-methyl ether also showed antinematodal activity against Bursaphelenchus xylophilus and Caenorhabditis elegans with IC50 values of 98.17MUg/mL and 74.62MUg/mL, respectively. This work is the first report on alternariol 9-methyl ether and its biological activities from the endophytic fungus Alternaria sp. Samif01 derived from S. miltiorrhiza Bunge. The results indicate the potential of Alternaria sp. Samif01 as a source of alternariol 9-methyl ether and also support that alternariol 9-methyl ether is a natural compound with high potential bioactivity against microorganisms. PMID- 26887232 TI - Structure of xanthan gum and cell ultrastructure at different times of alkali stress. AB - The effect of alkali stress on the yield, viscosity, gum structure, and cell ultrastructure of xanthan gum was evaluated at the end of fermentation process of xanthan production by Xanthomonas campestris pv. manihotis 280-95. Although greater xanthan production was observed after a 24h-alkali stress process, a lower viscosity was observed when compared to the alkali stress-free gum, regardless of the alkali stress time. However, this outcome is not conclusive as further studies on gum purification are required to remove excess sodium, verify the efficiency loss and the consequent increase in the polymer viscosity. Alkali stress altered the structure of xanthan gum from a polygon-like shape to a star like form. At the end of the fermentation, early structural changes in the bacterium were observed. After alkali stress, marked structural differences were observed in the cells. A more vacuolated cytoplasm and discontinuities in the membrane cells evidenced the cell lysis. Xanthan was observed in the form of concentric circles instead of agglomerates as observed prior to the alkali stress. PMID- 26887233 TI - Enzymatic saccharification and fermentation of cellulosic date palm wastes to glucose and lactic acid. AB - The bioconversion of cellulosic wastes into high-value bio-products by saccharification and fermentation processes is an important step that can reduce the environmental pollution caused by agricultural wastes. In this study, enzymatic saccharification of treated and untreated date palm cellulosic wastes by the cellulases from Geobacillus stearothermophilus was optimized. The alkaline pre-treatment of the date palm wastes was found to be effective in increasing the saccharification percentage. The maximum rate of saccharification was found at a substrate concentration of 4% and enzyme concentration of 30 FPU/g of substrate. The optimum pH and temperature for the bioconversions were 5.0 and 50 degrees C, respectively, after 24h of incubation, with a yield of 31.56mg/mL of glucose at a saccharification degree of 71.03%. The saccharification was increased to 94.88% by removal of the hydrolysate after 24h by using a two-step hydrolysis. Significant lactic acid production (27.8mg/mL) was obtained by separate saccharification and fermentation after 72h of incubation. The results indicate that production of fermentable sugar and lactic acid is feasible and may reduce environmental pollution by using date palm wastes as a cheap substrate. PMID- 26887234 TI - A new alkalophilic isolate of Bacillus as a producer of cyclodextrin glycosyltransferase using cassava flour. AB - Cyclodextrin glycosyltransferase (CGTase) catalyzes the conversion of starch into non-reducing cyclic sugars, cyclodextrins, which have several industrial applications. This study aimed to establish optimal culture conditions for beta CGTase production by Bacillus sp. SM-02, isolated from soil of cassava industries waste water lake. The optimization was performed by Central Composite Design (CCD) 2, using cassava flour and corn steep liquor as substrates. The maximum production of 1087.9UmL(-1) was obtained with 25.0gL(-1) of cassava flour and 3.5gL(-1) of corn steep after 72h by submerged fermentation. The enzyme showed optimum activity at pH 5.0 and temperature 55 degrees C, and maintained thermal stability at 55 degrees C for 3h. The enzymatic activity was stimulated in the presence of Mg(+2), Ca(+2), EDTA, K(+), Ba(+2) and Na(+) and inhibited in the presence of Hg(+2), Cu(+2), Fe(+2) and Zn(+2). The results showed that Bacillus sp. SM-02 have good potential for beta-CGTase production. PMID- 26887236 TI - Double mutation of Saccharomyces cerevisiae for enhanced beta-d fructofuranosidase fructohydrolase productivity and application of growth kinetics for parametric significance analysis. AB - The kinetics of an extracellular beta-d-fructofuranosidase fructohydrolase production by Saccharomyces cerevisiae in a chemically defined medium, i.e., sucrose peptone agar yeast extract at pH 6, was investigated. The wild-type was treated with a chemical mutagen, methyl methane sulfonate. Among the six mutants isolated, methyl methane sulfonate-V was found to be a better enzyme producing strain (52+/-2.4(a)U/mL). The maximum production (74+/-3.1(a)U/mL) was accomplished after at 48h (68+/-2.7(a)mg/mL protein). The mutants were stabilized at low levels of 5-fluoro-cytocine and the viable ones were further processed for optimization of cultural conditions and nutritional requirements. The sucrose concentration, incubation period and pH were optimized to be 30g/L, 28 degrees C, and 6.5, respectively. The methyl methane sulfonate-V exhibited an improvement of over 10 folds in enzyme production when 5g/L ammonium sulfate was used as a nitrogen source. Thin layer chromatography and high-performance liquid chromatography analysis illustrated the optimal enzyme activity supported by the higher rate of hydrolysis of sucrose into monosaccharides, particularly alpha-d glucose and beta-d-fructose. The values for Qp (2+/-0.12(c)U/mL/h) and Yp/s (4+/ 1.24(b)U/g) of the mutant were considerably increased in comparison with other yeast strains (both isolates and viable mutants). The mutant could be exploited for enzyme production over a wider temperature range (26-34 degrees C), with significantly high enzyme activity (LSD 0.048, HS) at the optimal temperature. PMID- 26887235 TI - Effects of oxygen transfer coefficient on dihydroxyacetone production from crude glycerol. AB - The principal objective of this study was to evaluate the kinetics of dihydroxyacetone production by Gluconobacter frateurii CGMCC 5397 under different oxygen volumetric mass transfer coefficient (kLa) conditions in submerged bioreactors using biodiesel-derived crude glycerol as the carbon source. kLa is a key fermentation parameter for the production of dihydroxyacetone. Cultivations were conducted in baffled- and unbaffled-flask cultures (the kLa values were 24.32h(-1) and 52.05h(-1), respectively) and fed-batch cultures (the kLa values were held at 18.21h(-1), 46.03h(-1), and 82.14h(-1)) to achieve high dihydroxyacetone concentration and productivity. The results showed that a high kLa could dramatically increase dihydroxyacetone concentrations and productivities. The baffled-flask culture (with a kLa of 52.05h(-1)) favored glycerol utilization and dihydroxyacetone production, and a dihydroxyacetone concentration as high as 131.16g/L was achieved. When the kLa was set to 82.14h( 1) in the fed-batch culture, the dihydroxyacetone concentration, productivity and yield were 175.44g/L, 7.96g/L/h and 0.89g/g, respectively, all of which were significantly higher than those in previous studies and will benefit dihydroxyacetone industrial production. PMID- 26887237 TI - Characterization of biotechnologically relevant extracellular lipase produced by Aspergillus terreus NCFT 4269.10. AB - Enzyme production by Aspergillus terreus NCFT 4269.10 was studied under liquid static surface and solid-state fermentation using mustard oil cake as a substrate. The maximum lipase biosynthesis was observed after incubation at 30 degrees C for 96h. Among the domestic oils tested, the maximum lipase biosynthesis was achieved using palm oil. The crude lipase was purified 2.56-fold to electrophoretic homogeneity, with a yield of 8.44%, and the protein had a molecular weight of 46.3kDa as determined by SDS-PAGE. Enzyme characterization confirmed that the purified lipase was most active at pH 6.0, temperature of 50 degrees C, and substrate concentration of 1.5%. The enzyme was thermostable at 60 degrees C for 1h, and the optimum enzyme-substrate reaction time was 30min. Sodium dodecyl sulfate and commercial detergents did not significantly affect lipase activity during 30-min incubation at 30 degrees C. Among the metal ions tested, the maximum lipase activity was attained in the presence of Zn(2+), followed by Mg(2+) and Fe(2+). Lipase activity was not significantly affected in the presence of ethylenediaminetetraacetic acid, sodium lauryl sulfate and Triton X-100. Phenylmethylsulfonyl fluoride (1mM) and the reducing, beta-mercaptoethanol significantly inhibited lipase activity. The remarkable stability in the presence of detergents, additives, inhibitors and metal ions makes this lipase unique and a potential candidate for significant biotechnological exploitation. PMID- 26887238 TI - Resistance patterns, ESBL genes, and genetic relatedness of Escherichia coli from dogs and owners. AB - Antimicrobial resistance in Escherichia coli isolated from pet dogs can be considered a potential threat of infection for the human population. Our objective was to characterize the resistance pattern, extended spectrum beta lactamase production and genetic relatedness of multiresistant E. coli strains isolated from dogs (n=134), their owners (n=134), and humans who claim to have no contact with dogs (n=44, control), searching for sharing of strains. The strains were assessed for their genetic relatedness by phylogenetic grouping and pulsed field gel electrophoresis. Multiresistant E. coli strains were isolated from 42 (31.3%) fecal samples from pairs of dogs and owners, totaling 84 isolates, and from 19 (43.1%) control group subjects. The strains showed high levels of resistance to ampicillin, streptomycin, tetracycline, trimethoprim and sulfamethoxazole regardless of host species or group of origin. The blaTEM, blaCTX-M, and blaSHV genes were detected in similar proportions in all groups. All isolates positive for bla genes were ESBL producers. The phylogenetic group A was the most prevalent, irrespective of the host species. None of the strains belonging to the B2 group contained bla genes. Similar resistance patterns were found for strains from dogs, owners and controls; furthermore, identical PFGE profiles were detected in four (9.5%) isolate pairs from dogs and owners, denoting the sharing of strains. Pet dogs were shown to be a potential household source of multiresistant E. coli strains. PMID- 26887239 TI - Isoflavone formononetin from red propolis acts as a fungicide against Candida sp. AB - A bioassay-guided fractionation of two samples of Brazilian red propolis (from Igarassu, PE, Brazil, hereinafter propolis 1 and 2) was conducted in order to determine the components responsible for its antimicrobial activity, especially against Candida spp. Samples of both the crude powdered resin and the crude ethanolic extract of propolis from both locations inhibited the growth of all 12 tested Candida strains, with a minimum inhibitory concentration of 256MUg/mL. The hexane, acetate and methanol fractions of propolis 1 also inhibited all strains with minimum inhibitory concentration values ranging from 128 to 512MUg/mL for the six bacteria tested and from 32 to 1024MUg/mL for the yeasts. Similarly, hexane and acetate fractions of propolis sample 2 inhibited all microorganisms tested, with minimum inhibitory concentration values of 512MUg/mL for bacteria and 32MUg/mL for yeasts. The extracts were analyzed by HPLC and their phenolic profile allowed us to identify and quantitate one phenolic acid and seven flavonoids in the crude ethanolic extract. Formononetin and pinocembrin were the major constituents amongst the identified compounds. Formononetin was detected in all extracts and fractions tested, except for the methanolic fraction of sample 2. The isolated isoflavone formononetin inhibited the growth of all the microorganisms tested, with a minimum inhibitory concentration of 200MUg/mL for the six bacteria strains tested and 25MUg/mL for the six yeasts. Formononetin also exhibited fungicidal activity against five of the six yeasts tested. Taken together our results demonstrate that the isoflavone formononetin is implicated in the reported antimicrobial activity of red propolis. PMID- 26887240 TI - Investigation of Helicobacter pylori antigen in stool samples of patients with upper gastrointestinal complaints. AB - Helicobacter pylori infection is usually acquired in early childhood and it can persist throughout life without antibiotic treatment. This study aimed to compare the accuracy of the noninvasive H. pylori Stool Antigen Test-applied on the stool samples with the invasive gold standart Rapid Urease Test-applied on the gastric biopy samples of patients with upper gastrointestinal complaints. After endoscopy, biopsy and stool specimens were taken in 122 patients. The infection was detected with rapid urease test which is accepted as gold standart test. Rapid, one-step H. pylori card test was applied to all patients stool specimens. In this study 106 of the 122 patients (86.8%) were positive for H. pylori infection, while 16 of the 122 patients (13.2%) were negative. H. pylori card test was negative in 13 of the 16 patients and was positive in 98 of the 106. The sensitivity, specifity, positive and negative predictive values were 92.45%, 81.25%, 97.02%, and 61.90%, respectively. H. pylori card test is rapid, easy, noninvasive and inexpensive methods for detection H. pylori infection. This test showed high sensitivity and specificity. Additionally, it may be a good alternative to invasive tests for the detection of H. pylori infections especially in children. PMID- 26887241 TI - Rapid detection of Candida species in bronchoalveolar lavage fluid from patients with pulmonary symptoms. AB - Candida species, especially C. albicans, are commensals on human mucosal surfaces, but are increasingly becoming one of the important invasive pathogens as seen by a rise in its prevalence in immunocompromised patients and in antibiotic consumption. Thus, an accurate identification of Candida species in patients with pulmonary symptoms can provide important information for effective treatment. A total of 75 clinical isolates of Candida species were obtained from the bronchoalveolar lavage fluid of both immunocompromised and immunocompetent patients with pulmonary symptoms. Candida cultures were identified based on nuclear ribosomal Internal Transcribed Spacer (ITS1-ITS2 rDNA) sequence analysis by polymerase chain reaction-restriction fragment length polymorphisms (PCR RFLP). Molecular identification indicated that the isolates belonged predominantly to C. albicans (52%), followed by C. tropicalis (24%), C. glabrata (14.7%), C. krusei (5.3%), C. parapsilosis (1.3%), C. kefyr (1.3%) and C. guilliermondii (1.3%). Given the increasing complexity of disease profiles and their management regimens in diverse patients, rapid and accurate identification of Candida species can lead to timely and appropriate antifungal therapy. PMID- 26887243 TI - Isolation, identification and characterization of regional indigenous Saccharomyces cerevisiae strains. AB - In the present work we isolated and identified various indigenous Saccharomyces cerevisiae strains and screened them for the selected oenological properties. These S. cerevisiae strains were isolated from berries and spontaneously fermented musts. The grape berries (Sauvignon blanc and Pinot noir) were grown under the integrated and organic mode of farming in the South Moravia (Czech Republic) wine region. Modern genotyping techniques such as PCR-fingerprinting and interdelta PCR typing were employed to differentiate among indigenous S. cerevisiae strains. This combination of the methods provides a rapid and relatively simple approach for identification of yeast of S. cerevisiae at strain level. In total, 120 isolates were identified and grouped by molecular approaches and 45 of the representative strains were tested for selected important oenological properties including ethanol, sulfur dioxide and osmotic stress tolerance, intensity of flocculation and desirable enzymatic activities. Their ability to produce and utilize acetic/malic acid was examined as well; in addition, H2S production as an undesirable property was screened. The oenological characteristics of indigenous isolates were compared to a commercially available S. cerevisiae BS6 strain, which is commonly used as the starter culture. Finally, some indigenous strains coming from organically treated grape berries were chosen for their promising oenological properties and these strains will be used as the starter culture, because application of a selected indigenous S. cerevisiae strain can enhance the regional character of the wines. PMID- 26887242 TI - Novel nonsense mutation in the katA gene of a catalase-negative Staphylococcus aureus strain. AB - We report the first description of a rare catalase-negative strain of Staphylococcus aureus in Chile. This new variant was isolated from blood and synovial tissue samples of a pediatric patient. Sequencing analysis revealed that this catalase-negative strain is related to ST10 strain, which has earlier been described in relation to S. aureus carriers. Interestingly, sequence analysis of the catalase gene katA revealed presence of a novel nonsense mutation that causes premature translational truncation of the C-terminus of the enzyme leading to a loss of 222 amino acids. Our study suggests that loss of catalase activity in this rare catalase-negative Chilean strain is due to this novel nonsense mutation in the katA gene, which truncates the enzyme to just 283 amino acids. PMID- 26887244 TI - Multidrug resistance and ESBL-producing Salmonella spp. isolated from broiler processing plants. AB - The aim of this study was to investigate the occurrence of multidrug-resistant, extended spectrum beta-lactamase (ESBL) producing Salmonella spp. isolated from conveyor belts of broiler cutting rooms in Brazilian broiler processing plants. Ninety-eight strains of Salmonella spp. were analyzed. Multidrug resistance was determined by the disk diffusion test and the susceptibility of the isolated bacteria was evaluated against 18 antimicrobials from seven different classes. The double disk diffusion test was used to evaluate ESBL production. Of the 98 strains tested, 84 were multidrug resistant. The highest rates of resistance were against nalidixic acid (95%), tetracycline (91%), and the beta-lactams: ampicillin and cefachlor (45%), followed by streptomycin and gentamicin with 19% and 15% of strain resistance, respectively. By contrast, 97% of the strains were sensitive to chloramphenicol. 45% of the strains were positive for the presence of ESBL activity. In this study, high rates of multidrug resistance and ESBL production were observed in Salmonella spp. PMID- 26887245 TI - Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil. AB - Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n=62) and human (n=67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6')-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6')-Ib. The conserved integron region was detected in 67 isolates as variable regions, from +/-600 to >1000pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored. PMID- 26887246 TI - Lactobacillus plantarum: Effect of a protective biofilm on the surface of olives during storage. AB - The aim of the present study was to investigate the effect of Lactobacillus plantarum adhesion to the surface of olives during storage through studying the interaction between the surfaces of the olives and L. plantarum. The results showed that the total number of adherent L. plantarum increased exponentially from 1.2*10(6) to 1.3*10(8)cfu/g. Images obtained using environmental scanning electron microscopy (ESEM) after 4 days of storage revealed that the olive surface was covered with a uniform and compact biofilm constituted of L. plantarum and yeast. Physicochemical analysis of surface of L. plantarum revealed that it was hydrophilic (Giwi>0mJ/m(2)). The surface of the olives also appeared to be hydrophilic (Giwi=3.28mJ/m(2)). The electron-donor characteristics of the surfaces of L. plantarum and olive were gamma(-)=53.1mJ/m(2) and gamma( )=28.1mJ/m(2), respectively. The formation of a protective biofilm of L. plantarum increased the hydrophilicity (from 3.28 to 46.14mJ/m(2)) and the electron-donor capacity (from 28.1 to 67.2mJ/m(2)) of the olive surface by 1 day of storage. Analysis of the impact of the biofilm that formed on the surface of the olives during storage showed a reduction in the content of undesirable planktonic microorganisms, such as fungi, which could have occurred due to competition for nutrients and oxygen or modifications in the physicochemical properties of the olives. Thus, coating the surface of olives with a natural material, such as L. plantarum, may be a first step in developing strategies to prevent their microbial colonization. PMID- 26887248 TI - Genotypic characterization of psittacid herpesvirus isolates from Brazil. AB - Thirty-six isolates of psittacid herpesvirus (PsHV), obtained from 12 different species of psittacids in Brazil, were genotypically characterized by restriction fragment length polymorphism (RFLP) analysis and PCR amplification. RFLP analysis with the PstI enzyme revealed four distinct restriction patterns (A1, X, W and Y), of which only A1 (corresponding to PsHV-1) had previously been described. To study PCR amplification patterns, six pairs of primers were used. Using this method, six variants were identified, of which, variants 10, 8, and 9 (in this order) were most prevalent, followed by variants 1, 4, and 5. It was not possible to correlate the PCR and RFLP patterns. Twenty-nine of the 36 isolates were shown to contain a 419bp fragment of the UL16 gene, displaying high similarity to the PsHV-1 sequences available in GenBank. Comparison of the results with the literature data suggests that the 36 Brazilian isolates from this study belong to genotype 1 and serotype 1. PMID- 26887247 TI - Virulence genes and antimicrobial resistance of Pasteurella multocida isolated from poultry and swine. AB - Pasteurella multocida causes atrophic rhinitis in swine and fowl cholera in birds, and is a secondary agent in respiratory syndromes. Pathogenesis and virulence factors involved are still poorly understood. The aim of this study was to detect 22 virulence-associated genes by PCR, including capsular serogroups A, B and D genes and to evaluate the antimicrobial susceptibility of P. multocida strains from poultry and swine. ompH, oma87, plpB, psl, exbD-tonB, fur, hgbA, nanB, sodA, sodC, ptfA were detected in more than 90% of the strains of both hosts. 91% and 92% of avian and swine strains, respectively, were classified in serogroup A. toxA and hsf-1 showed a significant association to serogroup D; pmHAS and pfhA to serogroup A. Gentamicin and amoxicillin were the most effective drugs with susceptibility higher than 97%; however, 76.79% of poultry strains and 85% of swine strains were resistant to sulphonamides. Furthermore, 19.64% and 36.58% of avian and swine strains, respectively, were multi-resistant. Virulence genes studied were not specific to a host and may be the result of horizontal transmission throughout evolution. High multidrug resistance demonstrates the need for responsible use of antimicrobials in animals intended for human consumption, in addition to antimicrobial susceptibility testing to P. multocida. PMID- 26887249 TI - Detection of seasonal asymptomatic dermatophytes in Van cats. AB - The Van cat is a domestic landrace found in the Van province of eastern Turkey. In this study, we aimed to determine the seasonal carriage of dermatophytes in Van cats without clinical lesions. A total of 264 hair specimens were collected from clinically healthy cats in and around the Van Province. Of these samples, 30.3% were obtained in spring, 30.6% in summer, 16.6% in autumn, and 22.3% in winter; 45.1% of samples were from male cats and the rest from female ones. Of the studied cats, 118 were younger than 1 year, 78 were 1-3 years old, and 68 were older than 3 years. The specimens were subjected to direct microscopic examination with 15% potassium hydroxide and cultured on Sabouraud dextrose agar and dermatophyte test medium supplemented with cycloheximide and chloramphenicol. Dermatophyte identification was carried out based on macroscopic and microscopic colony morphology, urease activities, in vitro hair perforation test, growth at 37 degrees C, and pigmentation on corn meal agar. Dermatophytes were isolated from 19 (7.1%) of the 264 specimens examined. The most frequently isolated fungi were Trichophyton terrestre (4.1%), followed by Microsporum gypseum (1.1%), M. nanum (1.1%), and T. mentagrophytes (0.7%), and these fungi may represent a health risk for humans in contact with clinically healthy Van cats. M. canis was not isolated from any of the specimens. Our results show no significant (p>0.05) association between carriage of dermatophytes and the gender of cats. The carriage rate of dermatophytes was high in spring and winter, and the only possible risk factor for infection was age of the animal. PMID- 26887250 TI - Experimental infection with Brazilian Newcastle disease virus strain in pigeons and chickens. AB - This study was designed with the goal of adding as much information as possible about the role of pigeons (Columba livia) and chickens (Gallus gallus) in Newcastle disease virus epidemiology. These species were submitted to direct experimental infection with Newcastle disease virus to evaluate interspecies transmission and virus-host relationships. The results obtained in four experimental models were analyzed by hemagglutination inhibition and reverse transcriptase polymerase chain reaction for detection of virus shedding. These techniques revealed that both avian species, when previously immunized with a low pathogenic Newcastle disease virus strain (LaSota), developed high antibody titers that significantly reduced virus shedding after infection with a highly pathogenic Newcastle disease virus strain (Sao Joao do Meriti) and that, in chickens, prevent clinical signs. Infected pigeons shed the pathogenic strain, which was not detected in sentinel chickens or control birds. When the presence of Newcastle disease virus was analyzed in tissue samples by RT-PCR, in both species, the virus was most frequently found in the spleen. The vaccination regimen can prevent clinical disease in chickens and reduce viral shedding by chickens or pigeons. Biosecurity measures associated with vaccination programs are crucial to maintain a virulent Newcastle disease virus-free status in industrial poultry in Brazil. PMID- 26887252 TI - Phylogenetic analysis of Dengue virus 1 isolated from South Minas Gerais, Brazil. AB - Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients who experience secondary infection with a different serotype can progress to a more severe form of the disease, called dengue hemorrhagic fever. The four Dengue virus serotypes (1-4) are antigenically and genetically distinct and each serotype is composed of multiple genotypes. In this study we isolated one Dengue virus 1 serotype, named BR/Alfenas/2012, from a patient with dengue hemorrhagic fever in Alfenas, South Minas Gerais, Brazil and molecular identification was performed based on the analysis of NS5 gene. Swiss mice were infected with this isolate to verify its potential to induce histopathological alterations characteristic of dengue. Liver histopathological analysis of infected animals showed the presence of inflammatory infiltrates, hepatic steatosis, as well as edema, hemorrhage and necrosis focal points. Phylogenetic and evolutionary analyses based on the envelope gene provided evidence that the isolate BR/Alfenas/2012 belongs to genotype V, lineage I and it is probably derived from isolates of Rio de Janeiro, Brazil. The isolate BR/Alfenas/2012 showed two unique amino acids substitutions (SER222THRE and PHE306SER) when compared to other Brazilian isolates from the same genotype/lineage. Molecular models were generated for the envelope protein indicating that the amino acid alteration PHE 306 SER could contribute to a different folding in this region located within the domain III. Further genetic and animal model studies using BR/Alfenas/2012 and other isolates belonging to the same lineage/genotype could help determine the relation of these genetic alterations and dengue hemorrhagic fever in a susceptible population. PMID- 26887251 TI - The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination. AB - Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p<0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p=0.598) and the total of negative samples for the remaining viruses tested (p=0.614). There was a significant association in the occurrence of infection in children aged 0-12 months for the condition 1 (p=0.030) as well as condition 2 (p=0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal distribution. These data indicate the significant involvement of HAdV-F type 41 in the etiology of ADD in Minas Gerais, which demonstrates the importance of other viral agents in the development of the disease after the introduction of rotavirus vaccine immunization. PMID- 26887254 TI - The dynamic structure of Spitzenkorpers of Trichosporon asahii examined by the fluorescent probe FM4-64. AB - The Spitzenkorper is a dynamic and specialized multicomponent cell complex present in the tips of hyphal cells. The amphiphilic styryl dye FM4-64 was found to be ideal for imaging the dynamic changes of the apical vesicle cluster within growing hyphal tips. It is widely used as a marker of endocytosis and to visualize vacuolar membranes. Here we performed uptake experiments using FM4-64 to study the dynamic of the Spitzenkorper in Trichosporon asahii. We observed that Spitzenkorpers were present at the tip of the budding site of the spore, blastospore, and the germ tube of T. asahii. We also found that Spitzenkorpers were present at the tip of the hyphae as well as the subapical regions. Cytochalasin D, an inhibitor of actin polymerization, leads to abnormal Spitzenkorper formation and loss of cell polarity. PMID- 26887255 TI - Development of a beetroot-based nutritional gel containing high content of bioaccessible dietary nitrate and antioxidants. AB - Beetroot, a food rich in nitrate and antioxidants has gained attention because of its potential effect on improving cardiovascular health and exercise performance. This work had the purpose of developing a beetroot-based nutritional gel (BG) and estimating the in vitro bioaccessibility of the nitrate, total antioxidant capacity (TAC), total phenolic (TP) and potassium content, as compared to beetroot juice (BJ). Nitrate was assessed by a high-performance liquid chromatography system, TAC was assessed using the Trolox equivalent antioxidant capacity (TEAC) assay and TP was measured using the Folin-Ciocalteu method before and after an in vitro digestion. Significantly higher values of nitrate, TEAC, TP and potassium before and after digestion were observed in BG as compared to BJ. The results suggest a new nutritional strategy to give high contents of bioaccessible nutrients (nitrate, antioxidants and potassium) that are potentially relevant to improve cardiovascular health and exercise performance. PMID- 26887253 TI - Selection of reference genes for expression analysis in the entomophthoralean fungus Pandora neoaphidis. AB - The selection of suitable reference genes is crucial for accurate quantification of gene expression and can add to our understanding of host-pathogen interactions. To identify suitable reference genes in Pandora neoaphidis, an obligate aphid pathogenic fungus, the expression of three traditional candidate genes including 18S rRNA(18S), 28S rRNA(28S) and elongation factor 1 alpha-like protein (EF1), were measured by quantitative polymerase chain reaction at different developmental stages (conidia, conidia with germ tubes, short hyphae and elongated hyphae), and under different nutritional conditions. We calculated the expression stability of candidate reference genes using four algorithms including geNorm, NormFinder, BestKeeper and Delta Ct. The analysis results revealed that the comprehensive ranking of candidate reference genes from the most stable to the least stable was 18S (1.189), 28S (1.414) and EF1 (3). The 18S was, therefore, the most suitable reference gene for real-time RT-PCR analysis of gene expression under all conditions. These results will support further studies on gene expression in P. neoaphidis. PMID- 26887256 TI - Detection of Matrilysin Activity Using Polypeptide Functionalized Reduced Graphene Oxide Field-Effect Transistor Sensor. AB - A novel approach for rapid and sensitive detection of matrilysin (MMP-7, a biomarker involved in the degradation of various macromolecules) based on a polypeptide (JR2EC) functionalized reduced graphene oxide (rGO) field effect transistor (FET) is reported. MMP-7 specifically digests negatively charged JR2EC immobilized on rGO, thereby modulating the conductance of rGO-FET. The proposed assay enabled detection of MMP-7 at clinically relevant concentrations with a limit of detection (LOD) of 10 ng/mL (400 pM), attributed to the significant reduction of the net charge of JR2EC upon digestion by MMP-7. Quantitative detection of MMP-7 in human plasma was further demonstrated with a LOD of 40 ng/mL, illustrating the potential for the proposed methodology for tumor detection and carcinoma diagnostic (e.g., lung cancer and salivary gland cancer). Additionally, excellent specificity of the proposed assay was demonstrated using matrix metallopeptidase 1 (MMP-1), a protease of the same family. With appropriate selection and modification of polypeptides, the proposed assay could be extended for detection of other enzymes with polypeptide digestion capability. PMID- 26887257 TI - Discourse level reading comprehension interventions following acquired brain injury: a systematic review. AB - Purpose Reading comprehension can change following acquired brain injury (ABI), impacting independence and participation. This review aims to identify and evaluate the interventions used for rehabilitation of discourse level reading in adults with ABI. Methods A systematic review was conducted of published journal articles. Methodological quality of studies was reviewed using formal and informal rating scales. Inclusion criteria involved adults with non-progressive ABI who experienced discourse level reading deficits related to aphasia or cognitive-communication disorders. Results A total of 23 studies were identified; these included randomized controlled trials, cohort and case studies. Six different types of reading interventions were found, overall results of these interventions were mixed. Reading deficits were reportedly related to language (aphasia) and/or cognitive deficits, with assessment processes varying. Questions arose regarding comparability of assessment methods and diagnostic issues across the studies. Conclusions Interventions for discourse level reading comprehension can make positive changes to reading function. However, no intervention was identified as a gold standard. A trend toward strategy-based reading was found, with these offering a potential for (comparatively) cost-effective lower-dosage reading treatments with positive-trend results. Cognitive and language features should be considered for assessment and intervention planning for discourse reading in ABI. Implications for Rehabilitation Six different types of discourse reading comprehension interventions for people with ABI were identified, with mixed evidence for each intervention. Clinicians need to consider both the linguistic and cognitive features of reading for assessment and intervention planning for discourse level reading. There is a research trend toward strategy based reading interventions, which use a lower treatment dosage. PMID- 26887259 TI - Review of Coping in Children Exposed to Mass Trauma: Measurement Tools, Coping Styles, and Clinical Implications. AB - Evidence-based practice requires the use of data grounded in theory with clear conceptualization and reliable and valid measurement. Unfortunately, developing a knowledge base regarding children's coping in the context of disasters, terrorism, and war has been hampered by a lack of theoretical consensus and a virtual absence of rigorous test construction, implementation, and evaluation. This report presents a comprehensive review of measurement tools assessing child and adolescent coping in the aftermath of mass trauma, with a particular emphasis on coping dimensions identified through factor analytic procedures. Coping measurement and issues related to the assessment of coping are reviewed. Concepts important in instrument development and psychometric features of coping measures used in disasters, terrorism, and war are presented. The relationships between coping dimensions and both youth characteristics and clinical outcomes also are presented. A discussion of the reviewed findings highlights the difficulty clinicians may experience when trying to integrate the inconsistencies in coping dimensions across studies. Incorporating the need for multiple informants and the difference between general and context-specific coping measures suggests the importance of a multilevel, theoretical conceptualization of coping and thus, the use of more advanced statistical measures. Attention also is given to issues deemed important for further exploration in child disaster coping research. PMID- 26887260 TI - [Oxidative stress and mitochondrion-related cell apoptosis in human bronchial epithelial 16HBE cells induced by silica dust]. AB - OBJECTIVE: To investigate oxidative stress and mitochondria-related cell apoptosis induced by silica dust in human normal bronchial epithelial 16HBE cells. METHODS: Cell viability, lactate dehydrogenase (LDH), superoxide dismutase (SOD), cell apoptotic rate, the expression level of Bax and Bcl-2 mRNA were measured after 16HBE cells were exposed to 37.5, 75, 150, 300 ug/mL respirable silica dust (diameter<2 um, d50=1 um)for 24 h in vitro. Reactive oxygen species (ROS)were tested after 16HBE cells were exposed to silica dust at above concentrations for 1.5, 3, 6, 12 h, respectively. RESULTS: Dose-dependent decreases of cell viability and the activity of SOD were observed when silica concentrations increased. The activity of LDH increased when silica concentrations elevated. Compared with the control group, cell viability significantly reduced in 75, 150, 300 ug/mL silica-treated groups (P<0.05). The activity of LDH significantly increased in 150, 300 ug/mL silica-treated groups when compared with the control group (P<0.05). The activity of SOD in all silica treated groups were significantly lower in comparison with controls (P<0.05). Intracellular ROS levels reached peak values at 1.5 h of silica exposure and gradually dropped to the base level at 12 h. The relationship between ROS levels and silica exposure were dose-response at 1.5 h, 3 h and 6 h of exposure (P<0.05). Similar dose-dependent increase were observed for apoptotic rate and silica exposure (P<0.05). The expression levels of Bcl-2 mRNA decreased, and the expression levels of Bax mRNA increased when silica concentrations increased. The results showed that significantly positive correlations between ROS level and apoptotic rate (r=0.892,P<0.05)or the expression level of Bax mRNA (r=0.850,P<0.05). There was a negative correlation between ROS level and the expression level of Bcl-2 mRNA (r=-0.703,P<0.05). CONCLUSION: Silica dust could induce cytotoxicity, oxidative stress and mitochondria-related cell apoptosis in 16HBE cells. Oxidative stress may play role in the processes of mitochondria related apoptosis. PMID- 26887261 TI - [The effect of Wnt signaling pathway on paraquat induced PC12 cells damage]. AB - OBJECTIVE: To investigate the role of Wnt signaling pathway on paraquat (PQ)induced PC12 cells damage. METHODS: Using PC12 cells, in this study CCK8 assay was used to detect the effect of cell viability. The cell apoptosis and cell cycle was detected by flow cytometry. The real-time polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of Wnt pathway key genes including Fzd1, Dvl2 and beta-catenin and downstream genes including Bax, Bcl2, Survivin, Cyclin D1 and C-myc. RESULT: Compared with the control, PC12 cells viability in 50.00 and 100.00 umol/L PQ treatment groups were obviously decreased, the cell cycle S phase arrest, and cell apoptosis increased (P<0.05). The 25.00, 50.00 and 100.00 umol/L PQ treatment groups mRNA expression of Wnt pathway key genes including Fzd1, Dvl2 and beta-catenin and downstream genes including apoptosis suppressor genes (Bcl-2 and survivin)and cyclin gene (Cyclin D1) were downregulated (P<0.05). The mRNA expression of pro-apoptosis gene (Bax) and cyclin gene (C-myc) were upregulated (P<0.05). CONCLUSION: It suggested that PQ can activate Wnt pathway to regulate downsteam genes expression, resulting in PC12 cell cycle arrest and apoptosis. PMID- 26887258 TI - Differential neutrophil responses to bacterial stimuli: Streptococcal strains are potent inducers of heparin-binding protein and resistin-release. AB - Neutrophils are critical for the control of bacterial infections, but they may also contribute to disease pathology. Here we explore neutrophil responses, in particular the release of sepsis-associated factors heparin-binding protein (HBP) and resistin in relation to specific bacterial stimuli and sepsis of varying aetiology. Analyses of HBP and resistin in plasma of septic patients revealed elevated levels as compared to non-infected critically ill patients. HBP and resistin correlated significantly in septic patients, with the strongest association seen in group A streptococcal (GAS) cases. In vitro stimulation of human neutrophils revealed that fixed streptococcal strains induced significantly higher release of HBP and resistin, as compared to Staphylococcus aureus or Escherichia coli. Similarly, neutrophils stimulated with the streptococcal M1 protein showed a significant increase in co-localization of HBP and resistin positive granules as well as exocytosis of these factors, as compared to LPS. Using a GAS strain deficient in M1-protein expression had negligible effect on neutrophil activation, while a strain deficient in the stand-alone regulator MsmR was significantly less stimulatory as compared to its wild type strain. Taken together, the findings suggest that the streptococcal activation of neutrophils is multifactorial and involves, but is not limited to, proteins encoded by the FCT-locus. PMID- 26887262 TI - [Anti-oncogene of opioid binding protein/cell adhesion molecule-like methylation status in malignant transformation of human bronchial epithelial cells induced by glycidyl methacrylate]. AB - OBJECTIVE: To analyze the opioid binding protein/cell adhesion molecule-like (OPCML) methylation status at different stages of malignant transformation of human bronchial epithelial (16HBE) cells induced by Glycidyl Methacrylate (GMA) and to explore the effect of OPCML methylation in the process of malignant transformation. METHODS: Cells were harvested at different stages (the 10th generation, the 20th generation and the 30th generation). To verify the Methylation chip result of OPCML methylation status in the process of malignant transformation, we detected it by methylation-specific-PCR (MSP); Real-time fluorescence Quantitative PCR (qPCR) were applied to measure the gene expression levels of OPCML at different transformed stage, and compared with the control groups (treated with DMSO). RESULTS: Based on the result of methylation chip, the gene of OPCML methylation occurred in all stages, which was consistent to the result of MSP; qPCR showed that the levels of gene expression decreased in the 20th generation and 30th generation. CONCLUSION: Methylation status of OPCML gene promoter could be considered as a stable and specific biomarker in the transformation process. PMID- 26887263 TI - [Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation by regulating acetylated tubulin alpha in silicotic rat model]. AB - OBJECTIVE: To explore the inhibition effect and mechanism of N-acetyl-seryl aspartyl-lysyl-proline (Ac-SDKP)on myofibroblast differentiation via regulating acetylated tubulin alpha (Ac-Tub alpha)in vivo and in vitro. METHODS: Silicotic model were made by SiO2 douched and divided into 6 groups as follows: control (4w, 8w)group, silicotic model (4w, 8w)group and post-or pre-treatment by Ac-SDKP group. Pulmonary fibroblasts were divided into 5 groups: (1) control; (2) Ang II; (3) Ang II+Ac-SDKP; (4) Ang II+Valsartan; (5) Ang II+TCS histone deacetylase (HDAC)6 20b. The localization of Ac-Tub alpha and alpha-smooth muscle actin (SMA) were observed by immunohistochemical (IHC) and immunofluorescence staining. The protein levels of Ac-Tub alpha, alpha-SMA, collagen type I (col I) and HDAC6 were measured by western blot. RESULTS: In silicotic nodules and interstitial fibrosis area, positive expression of alpha-SMA, a classical marker of myofibroblast, was ob-served by IHC, accompanied with absence expression of Ac-Tub alpha. Furthermore, Ac-SDKP post-treatment could attenuate the levels of col I, alpha SMA and HDAC6 to 48.39%, 52.63% and 70.18% compared with the silicotic 8w group respectively. And in Ac-SDKP pre-treatment group, compared with the silicotic 8w group, these protein levels were decreased to 32.26%, 64.91% and 54.39% respectively (P<0.05). The up-regulation of Ac-Tub alpha was found in Ac-SDKP post-and pre-treatment and increased to 3.00 and 2.90 folds compared with the silicotic 8w group. Compared with control group, the levels of alpha-SMA, HDAC6 and col I in Ang II group were up-regulated to 1.66, 3.56 and 4.00 folds accompanied with down-regulation of Ac-Tub by 44.44% (P<0.05). Pre-treatment with Valsartan, TCS HDAC6 20b or Ac-SDKP could inhibited all this changes induced by Ang II in vitro. CONCLUSION: Ac-SDKP can inhibit the myofibroblast differentiation and collagen deposition via sup-press HDAC6 and up-regulate the expression of Ac-Tub alpha in vivo and in vitro. PMID- 26887264 TI - [Comparison of two methods for fiber count concentration determination]. AB - OBJECTIVE: To compare the determination methods of fiber number concentration between China and WHO. METHODS: Individual fiber samplings were conducted at a RCF manufacturing enterprise for 40 types of work. Flow rate was set as 2 L/min and lasted 2 to 4 hours. We used acetone-triacetin to prepare samples. The rules of two methods were used to count fibers for each sample respectively. The differences between the results of two methods were compared using the sign-rank test, and the correlation between the two methods' counting results were evaluated by the Spearsman rank correlation analysis. RESULTS: The results of WHO counting rule were higher than those of Chinese counting rule for the same sample. The ratios of WHO method to Chinese method ranged from 1.88 to 3.70. Paired sign-rank test found the statistically significant differences of the results between the two methods (P<0.01). The rank correlation coefficient of the results by two rules counting ranged between 0.621 to 0.975, suggested positive correlation (P<0.01). The possible reasons of the difference between the two methods included the difference between the shapes of asbestos fiber and man-made mineral fiber, and counting rules of two methods. CONCLUSION: The results of WHO counting method is higher than those of Chinese counting method. High correlations between the results of the two methods were observed. PMID- 26887265 TI - [Comparison of welder's pneumoconiosis with silicosis and follow-up study of welder's pneumoconiosis]. AB - OBJECTIVE: To study the character of welder's pneumoconiosis on CT, pathology, and lung function. METHODS: To contrast 185 welder's pneumoconiosis and 115 silicosis on CT, pathology, and clinical characters which were diagnosed between Jan 2008 and Dec 2013. Chest X-ray and lung function of 39 welder's pneumoconiosis patients were followed up after diagnosed 4~6 years later. RESULTS: Average age and working years of welder's pneumoconiosis were 36.7 and 11.5, less than silicosis patients 58.8 and 22.1, respectively (P<0.05). Of all 185 welder's pneumoconiosis 98.4% were of stage I and no stage III, while in silicosis group stage I, stage II and stage III were 56.5%, 22.6% and 20.9%, respectively. The ratio differences between the two groups were statistically significant,P<0.05. 82.7% of welder's pneumoconiosis patients were observed pathologically moderate or above dust deposition in lung tissue while interstitial fibrosis level was just mild (97.6% patients) or no fibrosis (2.4% patients). By contrast, 60.0% silicosis patients pathologically showed moderate or above dust deposition while 77.8% were of moderate or above fibrosis. CT findings in welder' s pneumoconiosis were diffuse branching linear structure (38.9%), low density consistent size centrilobular micronodules (19.5%), or both (30.8%). Poorly-defined ground-glass attenuation centrilobular micronodules or widely ground glass shadow were observed in 6.4% welder's pneumoconiosis patents. 30.8% patients failed to reach the original stage when 39 welder's pneumoconiosis followed up chest radiograph. CONCLUSION: Changes in welder's lung caused by welding fume were not only siderosis, but also interstitial fibrosis. PMID- 26887266 TI - [Establishment of transbronchoscope whole lung lavage and its comparison with bronchoalveolar lavage and whole lung lavage]. AB - OBJECTIVE: To establish the technical specifications of transbronchoscope whole lung lavage (TBWLL) and to compare the clinical efficacy between TBWLL and bronchoalveolar lavage (BAL) or whole lung lavage (WLL). METHODS: A total of 133 patients with pneumoconiosis admitted to Hunan Prevention and Treatment Institute for Occupational Diseases from 2009 to 2014 were divided into TBWLL group (n=43), BAL group (n=45), and WLL group (n=45). Patients in the TBWLL group received conventional BAL of both lungs under a fiber bronchoscope, as well as sedation and anesthesia; lavage was performed twice in each course. TBWLL was compared with the BAL and WLL in terms of lavage volume. The clinical symptoms, pulmonary function, and blood gas before and after treatment and the safety were evaluated. RESULTS: The TBWLL group had significantly relieved cough and limitation of activity after lavage (P<0.05). Compared with the BAL group, the TBWLL group had significantly increased single lavage volumes and total lavage volume and a significantly shortened length of hospital stay (P<0.05). The three groups showed no significant short-term changes in clinical symptoms and pulmonary function after lavage. The TBWLL and WLL groups had a significantly lower incidence of postoperative complications than the BAL group (P<0.05). CONCLUSION: TBWLL has good clinical efficacy, with the advantages of BAL and WLL, and is highly feasible, safe, and effective. PMID- 26887267 TI - [Monitoring and analysis of asbestos concentration in working environment of different asbestos-producing technologies in a certain area]. AB - OBJECTIVE: To analyze asbestos exposure level between 1984 and 2010 in a district of malignant mesothelioma with clustering incidence in Zhejiang Province, in order to improve the recognizing and early diagnosis of malignant mesothelioma, protect the health of workers. METHODS: Monitoring data of total asbestos dust concentration in the air of workplace from 1984 to 2010 in asbestos textile enterprises, family hand spinning operation, brake production, and asbestos board production in Zhejiang Province were collected in the local CDC. A total of 766 TWA copies of mass concentration were collected, and 1233 copies of MAC data. Asbestos mass concentration and fibre counting concentration of 29 points of family hand spinning operation were parallel determinated in the same time and the same sampling point. Raw asesbtos materials and dust composition of local asbestos processing corporations were collected and analyzed using X-ray diffraction method. RESULTS: Raw materials of asbestos used between 1984 and 2010 in this area were chrysotile from Sichuan, Qinghai, Xinjiang, Russia, Zimbabwe, and some were mixed with SiO2, CaCO3 and other impurities. Raw materials used in asbestos board production were blue asbestos. Dust concentration between 1960s and 1980s in asbestos processing plants far exceeded the national standard. After then the dust concentration decreased significantly, but still higher than the national standard. 95.2% of air dust concentrations in the workplaces of asbestos factories exceeded the standard, and dust concentrations of workplaces of raw material, spinning, weaving, carding and labor insurance were above 90% in which carding work had the highest median concentration. 37.9% of dust mass concentrations in hand spinning work exceeded the standard where textile machinery side had the highest value. Beating job in asbestos board manufacturing and grinding job in brake production had higher concentrations. CONCLUSIONS: Most of production technologies in asbestos processing industry exceed the standard level, indicating that the workers were at risk for malignant mesothelioma and other asbestos related diseases, which should draw high attention. PMID- 26887269 TI - [Effects of mecobalamin on Bax and Bcl-2 in neurons after peripheral nerve injury]. AB - OBJECTIVE: To observe the effects of mecobalamin on the expression of apoptosis related proteins, Bax and Bcl-2, in neurons after peripheral nerve injury, and to explore the role of neuron apoptosis in peripheral nerve regeneration after injury. METHODS: Thirty healthy adult male wistar rats were randomly divided into sham-operation group, model group, and mecobalamin group, with 10 rats in each group. A rat model of left sciatic nerve semi-injury was established using forceps. Rats in the mecobalamin group were fed mecobalamin, while rats in the sham-operation group and model group were given the same dose of normal saline. The protein expression of Bax and Bcl-2 in neurons was measured at 14 days after operation. A semi-quantitative analysis of Bax and Bcl-2 proteins was performed by image analysis technology. RESULTS: The model group had significantly increased Bax protein expression and significantly reduced Bcl-2 protein expression in spinal cord anterior horn motor neurons and ganglion sensory neurons compared with the sham-operation group (P<0.05). Compared with the model group and sham-operation group, the mecobalamin group had significantly reduced Bax protein expression and significantly increased Bcl-2 protein expression in spinal cord anterior horn motor neurons and ganglion sensory neurons (P<0.05). CONCLUSION: Mecobalamin has anti-apoptotic effect, and it contributes to neurological function recovery possibly by inhibiting the death of injured neurons. PMID- 26887268 TI - [Effect of total flavonoids from astragalus complanatus on paraquat poisoning induced pulmonary fibrosis in rats and its mechanisms]. AB - OBJECTIVE: To investigate the effects of total flavonoids from astragalus complanatus (FAC) on paraquat poisoning-induced pulmonary fibrosis in rats. METHODS: The rats were divided into six groups randomly: control group, paraquat group, prednisolone group and FAC low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by intratracheal injection of paraquat. In the mext day,the rats were treated by intragastric administration once a day. After 28 days, the rats were sacrificed. The lung index and the levels of HYP and T-AOC were measured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-beta, Smad2, alpha-SMA protein were analyzed by Western blot. RESULTS: FAC improved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well (P<0.05 or P<0.01), the alveolitis and fibrosis extent were attenuated. The expression of Smad2 significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31+/-0.11, 0.45+/-0.12 and 0.30+/-0.05) as compared with that of the PQ group (0.85+/-0.34) (P<0.05). The expression of alpha-SMA significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31+/-0.11, 0.35+/-0.07 and 0.32+/-0.10) as compared with that of the PQ group (0.45+/-0.08) (P<0.05). The expression of TGF beta significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.35+/-0.04, 0.27+/-0.05 and 0.18+/-0.04)as compared with that of the PQ group (0.63+/-0.11) (P<0.05). CONCLUSION: FAC can alleviate PQ-induced pulmonary fibrosis in rats through inhibiting TGF-beta/Smad signaling pathway. PMID- 26887270 TI - [The rabbit experimental study for toxicokinetics of chlorpyrifos impacted by hemoperfusion]. AB - OBJECTIVE: To investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning. METHODS: 12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0. RESULTS: In hemoperfusion group, peak time was (7.19+/-3.74) h, peak concentrations was (1.37+/-0.56) mg/L, clearance rate was (13.93+/-10.27) L/h/kg, apparent volume of distribution was (418.18+/-147.15) L/kg The difference of these parameter were statistically significant compared with control group (P<0.05). CONCLUSION: Hmoperfusion will decrease the inner exposure and load dose of rabbits with chlorpyrifos poisoning. PMID- 26887271 TI - [One case with silicosis and diffuse panbronchiolitis]. PMID- 26887272 TI - [A case of intravenous paraquat induced poisoning death]. PMID- 26887274 TI - [Misdiagnosis of stage III cement pneumoconiosis]. PMID- 26887273 TI - [Isocyanurate exposure induced hypersensitivity pneumonitis]. PMID- 26887275 TI - [A case of oral trichloropropane and dichloropropane poisoning]. PMID- 26887276 TI - [A case of rhabdomyolysis, acute renal failure induced by paraquat poisoning]. PMID- 26887277 TI - [Rapid determination of 8 urinary carbamate pesticides by liquid chromatography tandem mass spectrometry]. AB - OBJECTIVE: To establish a method for simultaneously determining the urinary concentrations of 8 carbamate pesticides. METHODS: After being purified by acetonitrile precipitation, urine samples were transferred to a liquid chromatography-tandem mass spectrometry system, and the concentrations of 8 carbamate pesticides were determined by external standard method. A C18 column was used for ultra-high-performance liquid chromatography; methanol/ammonium acetate solution was used as the mobile phase for gradient elution; the mass spectrometer was operated in a multi-reaction monitoring mode. RESULTS: The calibration curves were linear when the urinary concentrations of these carbamate pesticides were 20~800 ug/L, and the recovery rates were 61.0%~121% at spiked levels of 20, 200 and 800 ug/L, with a relative standard deviation of 1.7%~5.5%. CONCLUSION: This determination method meets the Guide for establishing occupational health standards-part 5: Determination methods of chemicals in biological materials, and can be used for simultaneous determination of 8 carbamate pesticides in the urine of poisoning patients. PMID- 26887278 TI - [Guidelines for pathologic diagnosis of malignant mesothelioma--2012 update of the consensus statement from the International Mesothelioma Interest Group]. PMID- 26887279 TI - [Enlightenment of occupational medicine teaching for undergraduate in American and European countries]. PMID- 26887280 TI - [MicroRNAs in the diagnosis and therapy of malignant mesothelioma]. PMID- 26887281 TI - [Current status and challenges from therapeutic targeting of microRNAs]. PMID- 26887282 TI - [Recent progress on translocation of nanoparticles from lung to circulation system]. PMID- 26887283 TI - [Progress on analytical methods for benzene and its metabolites in human blood and urine]. PMID- 26887284 TI - Voltage collapse in complex power grids. AB - A large-scale power grid's ability to transfer energy from producers to consumers is constrained by both the network structure and the nonlinear physics of power flow. Violations of these constraints have been observed to result in voltage collapse blackouts, where nodal voltages slowly decline before precipitously falling. However, methods to test for voltage collapse are dominantly simulation based, offering little theoretical insight into how grid structure influences stability margins. For a simplified power flow model, here we derive a closed form condition under which a power network is safe from voltage collapse. The condition combines the complex structure of the network with the reactive power demands of loads to produce a node-by-node measure of grid stress, a prediction of the largest nodal voltage deviation, and an estimate of the distance to collapse. We extensively test our predictions on large-scale systems, highlighting how our condition can be leveraged to increase grid stability margins. PMID- 26887285 TI - Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis. AB - Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 degrees C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL( 1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug. PMID- 26887286 TI - Design of all-optical, hot-electron current-direction-switching device based on geometrical asymmetry. AB - We propose a nano-scale current-direction-switching device(CDSD) that operates based on the novel phenomenon of geometrical asymmetry between two hot-electron generating plasmonic nanostructures. The proposed device is easy to fabricate and economical to develop compared to most other existing designs. It also has the ability to function without external wiring in nano or molecular circuitry since it is powered and controlled optically. We consider a such CDSD made of two dissimilar nanorods separated by a thin but finite potential barrier and theoretically derive the frequency-dependent electron/current flow rate. Our analysis takes in to account the quantum dynamics of electrons inside the nanorods under a periodic optical perturbation that are confined by nanorod boundaries, modelled as finite cylindrical potential wells. The influence of design parameters, such as geometric difference between the two nanorods, their volumes and the barrier width on quality parameters such as frequency-sensitivity of the current flow direction, magnitude of the current flow, positive to negative current ratio, and the energy conversion efficiency is discussed by considering a device made of Ag/TiO2/Ag. Theoretical insight and design guidelines presented here are useful for customizing our proposed CDSD for applications such as self-powered logic gates, power supplies, and sensors. PMID- 26887287 TI - Influence of process dynamics on the microbial diversity in a nitrifying biofilm reactor: Correlation analysis and simulation study. AB - For engineers, it is interesting to gain insight in the effect of control strategies on microbial communities, on their turn influencing the process behavior and its stability. This contribution assesses the influence of process dynamics on the microbial community in a biofilm reactor for nitrogen removal, which was controlled according to several strategies aiming at nitrite accumulation. The process dataset, combining conventional chemical and physical data with molecular information, was analyzed through a correlation analysis and in a simulation study. During nitrate formation, an increased nitrogen loading rate (NLR) resulted in a drop of the bulk liquid oxygen concentration without resulting in nitrite accumulation. A biofilm model was able to reproduce the bulk liquid nitrogen concentrations in two periods before and after this increased NLR. As the microbial parameters calibrated for the ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in both periods were different, it was concluded that the increased NLR governed an AOB and NOB population shift. Based on the molecular data, it was assumed that each period was typified by one dominant AOB and probably several subdominant NOB populations. The control strategies for nitrite accumulation influenced the bulk liquid composition by controlling the competition between AOB and NOB. Biotechnol. Bioeng. 2016;113: 1962-1974. (c) 2016 Wiley Periodicals, Inc. PMID- 26887288 TI - G6PDH activity highlights the operation of the cyclic electron flow around PSI in Physcomitrella patens during salt stress. AB - Photosynthetic performances and glucose-6-phosphate dehydrogenase (G6PDH) activity in Physcomitrella patens changed greatly during salt stress and recovery. In P. patens, the cyclic electron flow around photosystem (PS) I was much more tolerant to high salt stress than PSII. After high salt stress, the PSII activity recovered much more slowly than that of PSI, which was rapidly restored to pretreatment levels even as PSII was almost inactivate. This result suggested that after salt stress the recovery of the cyclic electron flow around PSI was independent of PSII activity. In addition, G6PDH activity and NADPH content increased under high salt stress. When G6PDH activity was inhibited by glucosamine (Glucm, a G6PDH inhibitor), the cyclic electron flow around PSI and the NADPH content decreased significantly. Additionally, after recovery in liquid medium containing Glucm, the PSI activity was much lower than in liquid medium without Glucm. These results suggested the PSI activity was affected significantly by G6PDH activity and the NADPH content. Based on the above results, we propose that G6PDH in P. patens has a close relationship with the photosynthetic process, possibly providing NADPH for the operation of the cyclic electron flow around PSI during salt stress and promoting the restoration of PSI. PMID- 26887290 TI - Alteration in Phospholipidome Profile of Myoblast H9c2 Cell Line in a Model of Myocardium Starvation and Ischemia. AB - Myocardium infarction is one of the most deathly cardiovascular diseases. It is characterized by myocardium ischemia as a result of nutrients depletion and hypoxia. The cell can respond to this injury by autophagy or apoptosis, which determines the evolution and possible recovery of the myocardium infarction. Lipids play an important role in cardiovascular disease. However reports stating lipidome variations in cardiovascular disease are scarce and the role that lipids play in this pathological condition is not completely understood. The aim of this work was to identify changes in lipid profile of a myoblast H9c2 cell line under starvation and ischemia, to better understand and recognize new biomarkers for myocardial infarction. Lipidomic profile was evaluated by HILIC-LC-MS and GC-MS. Cardiac cells showed alterations in phosphatidylcholines PC (34:1) and PC (36:2), lysophosphatidylcholines lyso PC(16:0), lysoPC(18:1) and lysoPC(18:0), phosphatidylethanolamine PE (34:1), phosphatidylserine PS (36:1), phosphatidylinositol PI (36:2), PI (38:3) and PI (38:5), sphingomyelin SM (34:1) and cardiolipins CL(68:4), CL(72:5) and CL(74:7) in ischemia and/or starvation, in comparison with control. Specific differences observed only in starvation were decrease of SM (34:1) and FA (20:4), and increase of PS (36:1). Differences observed only in ischemia were decrease of PC (36:2), lyso PC (16:0) and FA (18:1) and simultaneous increase of FA (16:0), and FA (18:0). Interestingly, PC (34:1) increased in ischemia and decreased in starvation. In conclusion, our work suggests that lipids are potential markers for evaluation of cell fate, either cell death or recovery, which will be useful to improve diagnosis and prognostic of cardiovascular diseases. J. Cell. Physiol. 231: 2266-2274, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26887289 TI - Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. AB - OBJECTIVE: Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA mediator of signaling; NPRC-clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity. METHODS: A cross-sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12-week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10). RESULTS: NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P <= 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P <= 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARgamma coactivator-1alpha and uncoupling protein 1 (P <= 0.01). CONCLUSIONS: Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes. PMID- 26887291 TI - Large pinning forces and matching effects in YBa2Cu3O(7-delta) thin films with Ba2Y(Nb/Ta)O6 nano-precipitates. AB - The addition of mixed double perovskite Ba2Y(Nb/Ta)O6 (BYNTO) to YBa2Cu3O(7 delta) (YBCO) thin films leads to a large improvement of the in-field current carrying capability. For low deposition rates, BYNTO grows as well-oriented, densely distributed nanocolumns. We achieved a pinning force density of 25 GN/m(3) at 77 K at a matching field of 2.3 T, which is among the highest values reported for YBCO. The anisotropy of the critical current density shows a complex behavior whereby additional maxima are developed at field dependent angles. This is caused by a matching effect of the magnetic fields c-axis component. The exponent N of the current-voltage characteristics (inversely proportional to the creep rate S) allows the depinning mechanism to be determined. It changes from a double-kink excitation below the matching field to pinning-potential-determined creep above it. PMID- 26887294 TI - [Status of acute upper respiratory infection, influenza-like illness, and influenza vaccination coverage among community residents in Jinan]. AB - OBJECTIVE: To analyze the status of acute upper respiratory infection and influenza-like illness (ILI) among community residents in Jinan in 2015, and to make a understand of the patient's medical treatment behavior and influenza vaccination coverage status in 2014. METHODS: Balloting method and convenient sampling method were used to launch a household survey. The residents who had been in Jinan for more than 3 months were selected, to investigate the residents' attack ratio of acute upper respiratory and influenza-like from Jan. 8 to Feb. 7, 2015. Totally, 1 300 persons from 410 families were involved in this survey which recovered 1 241 valid questionnaires with the efficiency of 95.5%. Based on the national age-urban demographic statistics in 2010, the attack rates of acute respiratory infections, influenza-like illness were estimated by the direct standardization method, and the influenza vaccination rates were also calculated in this study. chi(2)-test method was used to compare the different status of incidence and vaccination among residents with different features. RESULTS: The attack rate of acute upper respiratory infection and influenza-like illness in Jinan from January 8, 2015 to February 7, 2015 were 30.2% (375 cases), and 6.1% (76 cases), respectively, with a standardized rate of 29.1% and 5.4%. 5.3% (66 cases) of the residents have vaccinated with the influenza vaccine inoculation, with an adjusted rate of 3.8%. The attack rate difference of acute upper respiratory tract infections was statistically significant between each age group (chi(2)=17.121, P= 0.002). The 0-4 age group had a highest attack rate (45.4%) of acute respiratory infection, while the 15-24 age group got the lowest (26.5%). 38.9% (146 cases) of patients went for a treatment in hospital. Among them, 37.7% (55 cases) of them selected the county level hospitals for treatment, 37.7% (55 cases) selected the community level hospitals, and 24.6% (36 cases) selected the individual clinic. Significant differences of influenza-like illness attack rate between each age group were also found in this study (chi(2)=76.79, P<0.001). 0-4 age group had the highest attack rate (22.7%). 81.6% (62 cases) of the ILI sought treatment in the hospital, of which 53.2% (33 cases) selected county level hospital or above, and 33.9% (21 cases) selected community hospital, and 12.9% (8 cases) selected the individual clinic. CONCLUSION: The attack rate of acute upper respiratory infections among the residents of Jinan was high, whereas that of influenza-like illness was relatively low. 0-4 age group had a higher risk of ILI than other age groups. Most of the cases were likely to take the treatment in large hospitals. In general, the coverage rate of influenza vaccination was relatively low. PMID- 26887293 TI - [Analysis of vaccination coverage of the elderly influenced by different family structures in Beijing]. AB - OBJECTIVE: To investigate the differences in free influenza vaccination rate among different family structures of the elderly population in Beijing under the free vaccination policy. METHODS: A cross sectional study was conducted by a multi-stage cluster sampling from July to August in 2013. A total of 1 717 individuals were selected to answer a self-designed questionnaire of demographic characteristics and basic information about receiving free influenza vaccination and 1 637 of which were valid. The chi-square test for dichotomous variables was calculated to examine the relationship between vaccine status and family characteristics. Predictor variables were selected as variables for non conditional logistic regression model to determine potential independent predictors of vaccine uptake. RESULTS: The free influenza vaccination rate in elderly population was 38.8% (634/1 637) in 2013. The rate in the old people who lived alone was the highest which was 47.5% (58/122). The rate in the old people who lived with children and spouse was 34.6% (175/506). There was a significant difference in coverage rate among different family structures (chi(2)=11.57, P=0.009). The rate in the old people who lived with spouse only, lived with children only and other types were 41.5% (322/778) , 34.7% (69/201), and 33.3% (10/30), respectively. In a multi-factor model, there was a significant difference in vaccination rate among different family structures after other confounding factors were controlled. The odds ratios (95% CI) of the people living with spouse only, people living with children only and people living with spouse and children were 0.90 (0.60-1.33) , 0.59 (0.37-0.96) , and 0.63 (0.42 0.96), respectively. CONCLUSION: The vaccination rate in the old people living alone was low. The health education should be conducted not only in the elderly people but also in their family members. PMID- 26887292 TI - How Tissue Mechanical Properties Affect Enteric Neural Crest Cell Migration. AB - Neural crest cells (NCCs) are a population of multipotent cells that migrate extensively during vertebrate development. Alterations to neural crest ontogenesis cause several diseases, including cancers and congenital defects, such as Hirschprung disease, which results from incomplete colonization of the colon by enteric NCCs (ENCCs). We investigated the influence of the stiffness and structure of the environment on ENCC migration in vitro and during colonization of the gastrointestinal tract in chicken and mouse embryos. We showed using tensile stretching and atomic force microscopy (AFM) that the mesenchyme of the gut was initially soft but gradually stiffened during the period of ENCC colonization. Second-harmonic generation (SHG) microscopy revealed that this stiffening was associated with a gradual organization and enrichment of collagen fibers in the developing gut. Ex-vivo 2D cell migration assays showed that ENCCs migrated on substrates with very low levels of stiffness. In 3D collagen gels, the speed of the ENCC migratory front decreased with increasing gel stiffness, whereas no correlation was found between porosity and ENCC migration behavior. Metalloprotease inhibition experiments showed that ENCCs actively degraded collagen in order to progress. These results shed light on the role of the mechanical properties of tissues in ENCC migration during development. PMID- 26887295 TI - [Changes of epidemiological characteristics of measles in Beijing before and after supplementary immunization campaigns of measles vaccine in 2010]. AB - OBJECTIVE: To investigate the changes of epidemiological characteristics of measles in Beijing before and after Supplementary Immunization Campaigns (SIA) (2007-2010 vs 2011-2014) of measles-containing vaccine (MCV) among children aged between 8 months and 14 years in 2010. METHODS: Descriptive epidemiological analysis was conducted on surveillance data of measles cases (clinical cases and laboratory confirmed cases), with the occurrence during 2007-2014, and of outbreaks, with the occurrence during 2009-2014, from National Notifiable Disease Reporting System. MapInfo geographic information system (Version 8.5) was used to illustrate the distribution of measles incidence by district. Annual measles incidence was classified into 5 groups at the same intervals between the upper and lower limits to analyze the morbidity of the different areas. RESULTS: In total, 7 722 and 3 132 measles cases were reported during 2007-2010 and 2011 2014, with the annual incidence of 11.59 and 3.84 cases per 100 000 population, respectively. Comparing with the results during 2007-2010, total number of measles cases and average annual incidence during 2011-2014 were decreased by 59.4%, and 66.9%, respectively. Among measles cases during 2011-2014, percentage of cases aged 15 years or above were 57.7%(56/97), 62.0%(49/79), 65.5%(370/565), and 71.4% (1 707/2 391), respectively, which increased by years. During 2007 2010, the highest risk age for adults was 20-34, while 2011-2014, 5 years older: 25-39. During 2009-2010, 2011-2012, and 2013-2014, 50.3% (447/889), 30.3% (10/33), and 57.8% (201/348), respectively, of measles cases aged 8-17 months were unvaccinated by MCV. Percentages of measles cases aged 0-7 months, 8 months 14 years, 15-39 years and 40 years or above during 2013-2014, who visited hospitals 7-21 days before disease onset, were 59.8% (238/398), 49.3% (237/481), 32.2% (529/1641), and 37.6% (164/436), respectively. A total of 11 nosocomial measles outbreaks occurred during 2013-2014, which was much higher than that during 2009-2010 (2 nosocomial outbreaks). And universities accounted for the majority of outbreak settings of schools (3/4). All 11 outbreaks among grouped employees during 2009-2012 occurred in factories, restaurants, or large shopping centers, while the largest proportion (6/16) of that kind of outbreaks during 2013-2014 occurred in office buildings. CONCLUSIONS: SIA of MCV in 2010 effectively decreased measles transmission in Beijing. But routine immunization of MCV still needed to be improved. The issue of adult measles has been a prominent problem. Hospitals, office buildings and universities were the focus of prevention of measles transmission. PMID- 26887296 TI - [Application of multiple seasonal autoregressive integrated moving average model in predicting the mumps incidence]. AB - OBJECTIVE: To establish multiple seasonal autoregressive integrated moving average model(ARIMA) according to mumps disease incidence in Hunan province, and to predict the mumps incidence from May 2015 to April 2016 in Hunan province by the model. METHODS: The data were downloaded from "Disease Surveillance Information Reporting Management System" in China Information System for Disease Control and Prevention. The monthly incidence of mumps in Hunan province was collected from January 2004 to April 2015 according to the onset date, including clinical diagnosis and laboratory confirmed cases. The predictive analysis method was the ARIMA model in SPSS 18.0 software, the ARIMA model was established on the monthly incidence of mumps from January 2004 to April 2014, and the date from May 2014 to April 2015 was used as the testing sample, Box-Ljung Q test was used to test the residual of the selected model. Finally, the monthly incidence of mumps from May 2015 to April 2016 was predicted by the model. RESULTS: The peak months of the mumps incidence were May to July every year, and the secondary peak months were November to January of the following year, during January 2004 to April 2014 in Hunan province. After the data sequence was handled by smooth sequence, model identification, establishment and diagnosis, the ARIMA(2,1,1) * (0,1,1)(12) was established, Box-Ljung Q test found, Q=8.40, P=0.868, the residual sequence was white noise, the established model to the data information extraction was complete, the model was reasonable. The R(2) value of the model fitting degree was 0.871, and the value of BIC was -1.646, while the average absolute error of the predicted value and the actual value was 0.025/100 000, the average relative error was 13.004%. The relative error of the model for the prediction of the mumps incidence in Hunan province was small, and the predicting results were reliable. Using the ARIMA(2,1,1) *(0,1,1)(12) model to predict the mumps incidence from April 2016 to May 2015 in Hunan province, the peak months of the mumps incidence were May to July, and the secondary peak months were November to January of the following year, the incidence of the peak month was close to the same period. CONCLUSION: The ARIMA(2,1,1)*(0,1,1)(12) model is well fitted the trend of the mumps disease incidence in Hunan province, it has some practical value for the prevention and control of the disease. PMID- 26887297 TI - [Analysis of seroepidemiology of enterovirus 71 diseases in children in Jiangsu province]. AB - OBJECTIVE: To analyze the dynamic pattern and the distributive characteristics of neutralizing antibody against enterovirus 71 (EV-A71 ) in children aged 6-35 months in Jiangsu province from 2012 to 2014. METHODS: From March, 2012 to March, 2014, a total of 1 276 children aged between 6 and 35 months were regularly followed up on day 0, year 1 and year 2 for EV-A71 neutralizing antibody test based on the enterovirus surveillance system, with the method of reporting by their guardian or being visited in Ganyu Sheyang Taixing Donghai Pizhou and Baoying in Jiangsu province. At the same time, samples were taken from the suspected persons infected by enterovirus. The chi(2) test or variance analysis was used to compare the difference of the positive rates and the geometric mean titer(GMT) of EV-A71 neutralizing antibody in different subjects. RESULTS: In 2 years follow-up, the positive rates of EV-A71 antibody increased as the growth of the age,and the positive rates on day 0, year 1 and year 2 were 22.57% (288/1 276), 37.72%(444/1 177) and 42.84%(422/985), respectively (chi(2) values were 39.33, 56.41, 32.25; P< 0.001).The GMTs were 9.95, 15.37 and 24.05, respectively (F values were 22.90,46.36,41.58;P<0.001). In 2 years, the annually new infection rates were 13.47%(158/1 173) and 20.73%(192/926),respectively, and the annually decay rates of EV-A71 antibody were 2.81%(33/1 173) and 8.10%(75/926). CONCLUSIONS: In 2012 to 2014, the positive rates and the GMTs of EV-A71 antibody of children increased as the growth of the age in Jiangsu. The higher annually new infection rate was in children aged 3 to 4 years. The EV-A71 neutralizing antibody level could maintain at least two years after natural infection. PMID- 26887298 TI - [Short term effect of weather patterns on the incidence of hand foot and mouth disease aged <=5 years old in Jinan city]. AB - OBJECTIVE: To investigate the effect of weather patterns on the incidence of hand foot and mouth disease (HFMD) in Jinan. METHODS: HFMD confirmed cases aged <=5 years old for the period of 2012-2014 were collected from National Notifiable Disease Report System (NNDRS). Simultaneous meteorological data, including daily average temperature, relative humidity, atmospheric pressure, wind velocity, rainfall and duration of sunshine were obtained from the website of Jinan meteorological bureau. A negative binomial multivariable regression was used to identify the relationship between meteorological variables and HFMD. RESULTS: During the study period, a total of 40 405 HFMD cases aged <=5 years old were reported. The incident peak occurred from May to July, a total of 22 254 cases were reported during this period, which accounted for 55.08% of whole cases. After adjusting by "year", each 1 degrees C rise of weekly average temperature corresponded to an increase of 6.70% (95%CI:6.35% to 7.06%) in the weekly number of HFMD cases, while a 1 kPa rise of weekly average atmospheric pressure corresponded to a decrease in the number of cases by 44.77% (95%CI: -46.23% to 41.91%). Likewise, a one percent rise in weekly average relative humidity corresponded to an increase of 1.96% (95%CI: 1.84% to 2.09%), a 1 m/h rise in weekly average wind velocity corresponded to an increase of 16.63% (95% CI:14.08% to 19.25%), a hour add in weekly duration of sunshine corresponded to a decrease of 0.82% (95% CI : -0.93% to -0.72%), in the weekly number of HFMD cases. CONCLUSION: Weather factors including temperature, atmospheric pressure, relative humidity, wind velocity, and duration of sunshine had a significant influence on occurrence and transmission of HFMD in Jinan city. PMID- 26887299 TI - [Genetic characteristics of VP1 region of coxsackievirus A10 strains in Ningxia Hui Autonomous Region during 2013-2014]. AB - OBJECTIVE: To investigate the genetic characteristics of coxsackievirus A10(CV A10) strains isolated from hand, foot and mouth disease (HFMD) cases in Ningxia province. METHODS: Based on the HFMD laboratory network surveillance system, 2 470 patients clinical specimens including 450 faeces and 2 020 throat swaps were collected from various regions people's hospital in Ningxia Hui Autonomous Region during January, 2013 to December, 2014. All specimens were isolated using rhabdomyosarcoma cells. VP1 regional gene of isolated strains was amplified by RT PCR using degenerate primers and sequenced. Sequences were compared with the database of GenBank by the Blast algorithm to identify the enterovirus genotypes. All the CV-A10 strains were performed the homology and phylogenetic evolution analysis. RESULTS: 450 specimens identified as non-EV-A71, non-CV-A16 enterovirus were collected and 36 CV-A10 strains were isolated, 6 strains were isolated in 2013 and 30 strains were isolated in 2014. The homology of nucleotides and amino acids among 36 CV-A10 strains were 90.6%-100.0% , and 90.2%-100.0%, respectively. Compared 36 strains with genotype A, B, C, D representative strains, it has the highest homology with the genotype C, the nucleotide and amino acids homogeneity were 90.2%-98.9% and 95.7%-99.7%. The phylogenetic tree showed 36 strains and genotype C representative strains located in the same evolutionary branch. CONCLUSION: CV-A10 was one of the most common pathogen of HFMD in Ningxia Hui Autonomous Region. All CV-A10 strains belonged to genotype C and contained wide homology range. PMID- 26887300 TI - [Survival analysis of AIDS patients of 15 years or above years old after initiation antiretroviral treatment in Henan province during 2005 to 2014]. AB - OBJECTIVE: To investigate the survival rate of AIDS patients after receiving antiretroviral therapy(ART) in Henan province and to determine factors associated with survival status. METHODS: Database of AIDS patients receiving ART were downloaded from China Information System for Disease Preventioin and Control AIDS, retrospective study method was conducted to analyze the information. INCLUSION CRITERIA: initially received national free ART during January, 2005 to December, 2014; aged 15 years or above; and with relatively complete baseline information and follow-up information. The accumulated survival rate of AIDS patients was calculated by life table method and the influencing factors were analyzed by Cox proportional hazard model. RESULTS: Total 30 376 AIDS patients were enrolled in this study. During the follow-up period, a total of 3 927 cases died from HIV/AIDS related diseases. The mortality of all patients was 3.2/100 person year. After 1, 5, 10 years after the initiation of ART, the rates of accumulate survival rate were 93.7%, 85.3%, and 78.4%, respectively. Stepwise regression was used to conduct the time multiple factors analysis, the results showed that man (HR=1.28, 95%CI: 1.20-1.37), older age (HR=1.20, 95% CI: 1.16 1.24), others marital status except marrage or cohabitation (HR=1.20,95% CI: 1.12 1.29), more number of symptoms (HR=1.11, 95%CI: 1.07-1.14), initial treatment were main stavudine (D4T) or zidovudine (AZT)+ didanosine(DDI)+ nevirapine (NVP) or efevirenz (EFV) (HR=1.12, 95% CI: 1.04-1.20), missing drug in the past 7 days (HR=18.36,95%CI: 17.08-19.74) among AIDS patients had high mortality risk, homosexuality sexual transmission (HR=0.59, 95% CI: 0.40-0.87), higher baseline count of CD4(+)T lymphocyte (relative to 0-200 cells/ul group, HR (95%CI) were 0.57 (0.53-0.62), 0.43(0.37-0.49), 0.33 (0.27-0.40) in 201-350 cells/ul group, 351-500 cells/ul group, and >=501 cells/ul group, respectively), higher educations (HR=0.89, 95% CI: 0.83-0.95) had low mortality risk. CONCLUSION: Survival rate was higher after initial antiretroviral treatment among AIDS patients in Henan province. AIDS patient will have shorter survival time after antiviral treatment under one or more following conditions: higher age, male, initial treatment with D4T or AZT + DDI + NVP or EFV, lower baseline CD4 (+) T lymphocyte count, ever missed antiviral drugs in past 7 days of latest follow-up. PMID- 26887301 TI - [Contact tracing of pregnant women infected with syphilis and the associated factors]. AB - OBJECTIVE: To investigate the current status of contact tracing among pregnant women infected with syphilis and to analyze the associated factors from patients' perspective. METHODS: Pregnant women who aged 18 years old, receiving prenatal care services in Shenzhen, diagnosed with syphilis according to national diagnostic criteria (WS 273-2007) from 2008 to 2011 were recruited and the total number was 3 551. Information of both pregnant women (including demographic information, laboratory results, syphilis diagnosis, and personal life history) and their partners (including results of partner tracing and laboratory examination) were collected with structured questionnaire by face-to-face interview. Multivariate non-conditional logistic regression model was applied to analyze the factors associated with partners' contract tracing. Odds ratio (OR) and its 95% confidential interval (95%CI) were calculated. RESULTS: The average age was 28.72 among recruited 3 551 syphilis-infected pregnant women, with standard deviation of 5.21 and range of 18 to 40. Totally 2 550 partners attended antenatal clinics and received syphilis examination, with a contact tracing rate of 71.81%. The OR(95%CI) was 1.70(1.26-2.30) for pregnant women with college or above education when comparing with those with senior high school or below education. The OR(95%CI) was 0.57(0.45-0.71) for those unmarried or divorce when comparing with those married. The OR (95% CI) was 0.73(0.56-0.94) and 0.65(0.53 0.81) for those screened in 28-36 gestational weeks and those screened in >36 gestational weeks or right before delivery separately, when comparing with those screened in <=27 gestational weeks. The OR (95% CI) was 1.45(1.14-1.84) for those having received sufficient treatment before pregnancy when comparing with those diagnosed with latent syphilis. The OR(95%CI) was 0.31 (0.24-0.39) for those having no treatment or not standardized treatment when comparing with those having standardized penicillin treatment. The OR(95%CI) was 0.53 (0.43-0.65) for those terminating the pregnancy when comparing with those giving birth to a baby. The OR(95%CI) was 1.24 (1.05-1.46) for those having two or more love histories when comparing with those having only one love history. The OR(95%CI) was 4.74 (3.54-6.35) for those intending to disclose the serostatus to their partner when comparing with those showing unwillingness to disclose the serostatus. CONCLUSION: The successful rate of contact tracing among pregnant women infected with syphilis was high. The implementation of contact tracing may be affected by many factors, including patients' education levels, marital status, gestational weeks of screening, stage of syphilis, treatment status, outcome of pregnancy, number of love histories, and willingness of serostatus disclosure. PMID- 26887302 TI - [The negative psychology for the public in Zhejiang province during the epidemic of human H7N9 avian influenza]. AB - OBJECTIVE: To evaluate the cognition and emotional response of the public in Zhejiang province during the epidemic of human H7N9 avian influenza and provide scientific support for group psychological intervention under public health emergency. METHODS: 57 communities in 19 counties from Hangzhou, Jiaxing and Lishui district of Zhejiang province were selected as survey sites using stratified clustered sampling method from March, 2013 to April, 2014. 2 319 ordinary civilians were chosen using convenience sampling method and 390 individuals who had close contact history with H7N9 avian influenza patients, 109 family members of patients and 281 medical workers, were selected using census method. The inclusion criteria for subjects were: subjects aged over 10 years; could complete the questionnaire independently or with the help of the investigators. A total of 2 709 subjects were surveyed by avian influenza risk perception and response questionnaire, negative emotion questionnaire was also used to see their cognition and negative emotion related to the disease. Spearman correlation analysis was used to analyze the interrelationship between public risk perception, response and negative emotions. RESULTS: 95.10% (2 576)of the subjects have sensed the risk of epidemic and 91.00% (2 465) of the subjects have taken preventive measures in 2 709 subjects. The positive rate for depression, neurasthenia, fear, anxiety and hypochondriasis were 36.40% (986) , 37.21% (1 008) , 79.70% (2 159) , 33.41% (905) , 27.69% (750) respectively (chi(2)=1 935.89, P<0.001) ;the P(50)(P(25)-P(75)) of the depression scores of patients' family members, medical workers and the general public were 0.50 (0.00-0.83), 0.17 (0.00-0.67), 0.17 (0.00-0.50) (H= 7.27, P=0.03) ; the neurasthenia scores were 0.20 (0.00-0.60), 0.2 (0.00-0.40), 0.00 (0.00-0.20) (H= 64.74, P<0.001) ; fear scores were 0.83 (0.33-1.17), 0.33 (0.17-0.67), 0.33 (0.17-0.83) (H=30.03, P< 0.001) ; anxiety scores were 0.17(0.00-0.50), 0.00(0.00-0.33), 0.00(0.00-0.17) (H=51.82, P<0.001). The neurasthenia, fear, anxiety scores (P(50)(P(25)-P(75))) for females among the public were 0.00(0.00-0.20), 0.50(0.17-0.83), 0.00(0.00 0.17), which were higher than those of male's (0.00(0.00-0.20), 0.33(0.00-0.67), 0.00(0.00-0.17)) (chi(2) values were 5.26, 27.52, 8.29, P<0.05); Among medical staff, the depression, neurasthenia, fear, anxiety and hypochondriasis scores for females were 0.33(0.00-0.67), 0.20(0.00-0.40), 0.50(0.17-0.83), 0.00(0.00-0.33), 0.00(0.00-0.50) respectively, which were higher than those of males'(0.00(0.00 0.50), 0.00(0.00-0.40), 0.33(0.17-0.50), 0.00(0.00-0.17), 0.00(0.00-0.00))(chi(2) values were 7.22, 7.97, 14.46, 4.93, 5.22, P<0.05); for the family members of the patients who were in poor mental conditions when doing self-assessment, their depression and neurasthenia scores were 0.50(0.08-0.96), 0.30(0.00-0.55), which were higher than those of people in good mental conditions (0.17(0.00-0.83), 0.20(0.00-0.60)) (chi(2) values were 12.95, 11.20, P<0.05). Spearman correlation analysis showed that the subjects' risk perception level was positively correlated with depression, neurasthenia, fear, and hypochondriasis, with the correlation coefficients 0.07, 0.07, 0.08, 0.04, respectively (P<0.05) ; the subjects' risk response level was also positively related with depression, neurasthenia, fear, anxiety and hypochondriasis, and the correlation coefficients were 0.09, 0.09, 0.12, 0.05, 0.04, respectively (P<0.05). CONCLUSION: The general public was highly concerned about the epidemic of H7N9 avian influenza and developed certain levels of negative emotions. The female, equal or over 60 years old, those with poor educational level, agricultural related occupation and poor physical and psychology health were risk factors of disease related negative emotions. The subject's risk perception and response level was positively related with depression, neurasthenia, fear and hypochondriasis. PMID- 26887303 TI - [Effects of occupational stress and related factors on depression symptoms in train drivers]. AB - OBJECTIVE: To explore the influence of occupational stress and related factors on depression symptoms in train drives. METHODS: In March 2012, by using cluster sampling method, a cross-sectional epidemiological study was conducted in 1 402 train drivers in China. Questionnaires was investigation was conducted by face to face interview. Sample with missing variables on demographic characteristics questionnaire with missed survey variables, and occupational stress related factors and with over 3 item missing in depression symptoms self-rating scale were exclued. Depression symptoms were measured by Center for Epidemiological Survey Depression Scale. The occupational stress related actors were measured by the revised effort-reward imbalance (ERI) model questionnaires and occupational stress measurement scale. Chi-square test was carried out to analyze the differences of the incidence of depressive symptoms among different general characteristics groups, and multivariate logistic regression analysis was conducted to analyze the influence of occupational stress and related factors on depression symptoms in train drivers. RESULTS: The study showed that the average age of 1 402 subjects was (34.95+/-9.20) years, the length of service were (13.28+/-9.78) years, the score of depressive symptoms was (24.14+/-5.98) scores. 902 subjects (64.3%,902/1 402) were classified as people with depressive symptoms, the incidence of depressive symptoms in EMU or high-speed train drivers were the highest (68.0%,51/75); Incidence of depressive symptoms showed that were statistically significant differences in two groups of technical secondary school and college, and incidence of depressive symptoms in the junior college and above group (68.1%,352/517) was higher than that in the senior high school and below group (62.1%, 550/885) (chi(2)=5.02, P=0.025). The results of the multiple logistic regression analysis revealed that high levels of education (OR=1.63, 95%CI: 1.12-2.19), role conflict (OR=1.65, 95% CI: 1.21-2.24), role ambiguity (OR=1.99, 95% CI: 1.45-2.73), negative emotion(OR=2.87, 95%CI: 2.15-3.82), daily tension(OR=2.86, 95%CI: 2.11-3.86), poor colleagues and family support (OR=1.55, 95% CI: 1.11-2.16 and OR=1.75, 95% CI: 1.27-2.41) were risk factors of depressive symptoms, but positive emotion (OR=0.72, 95% CI: 0.53-0.96), self-esteem (OR=0.22, 95% CI: 0.16-0.30), and job itself satisfaction (OR=0.48, 95%CI: 0.35 0.65) were protective factors of depressive symptoms in train drivers. CONCLUSION: Train drivers, in particular EMU or high-speed train drivers who were prone to depressive symptoms. To arrange reasonably job roles and tasks, increase support from superiors, colleagues, and family, bring up healthy and coordinated personality, keep a good mood, promote job satisfaction, reduce the daily tension have positive effects on reducing the occurrence of depressive symptoms for train drivers. PMID- 26887304 TI - [Acute effects of SO2 and NO2 on mortality in the six cities of China]. AB - OBJECTIVE: To explore acute effects of SO(2) and NO(2) on mortality in the six cities of China. METHODS: Surveillance data on daily air quality, meteorology and the cause of death were collected from January 1, 2007 to December 31, 2009 in Beijing, Tianjin, Xi'an, Shanghai, Guangzhou and Wuhan. Generalized additive model was used to explore the relationship between the daily average concentration of SO(2) and NO(2) and daily mortality, after adjusting the effects of long-term and seasonal trend and weather conditions. RESULTS: In Beijing, Tianjin, Xi'an, Shanghai, Guangzhou and Wuhan, the daily average concentration of SO(2) and NO(2) were in the range of 39.8-59.5 ug/m(3) and 41.4-60.1 ug/m(3) respectively; the daily mortality for non-accidental were 174.5, 101.4, 27.7, 108.4, 50.6, 17.8, cardiovascular were 86.9, 53.3, 12.8, 34.8, 16.3, 8.1 and respiratory were 18.3, 8.6, 2.6, 18.6, 9.0, 1.8 respectively. The daily average concentration of SO(2) were negatively correlated with daily average temperature in Beijing, Tianjin, Xi'an and Wuhan (the correlation coefficients were -0.66, 0.73, -0.67 and -0.39 respectively, P<0.05). The daily average concentration of SO(2) were negativeiy correlated with relative humidity in Tianjin, Shanghai and Wuhan (the correlation coefficients were -0.26, -0.46 and -0.28 respectively, P<0.05). The daily average concentration of NO(2) were negative correlated with daily average temperature in Beijing, Tianjin, Xi'an and Wuhan (the correlation coefficients were -0.27, -0.49, -0.45 and -0.38 respectively, P<0.05). When the day concentration of SO(2) increased every 10 ug/m(3), the non-accidental mortality in Tianjin and Wuhan raised 0.44%(95%CI: 0.11%-0.78%) and 0.96%(95%CI: 0.22%-1.72%) respectively. When the 1 day-lag concentration of SO(2) increased every 10 ug/m(3), the non-accidental mortality in Shanghai, Guangzhou and Wuhan raised 0.28% (95% CI: 0.02%-0.54% ), 0.41% (95% CI: 0.04%-0.79% ) and 1.14% (95% CI: 0.44%-1.84%) respectively. When the day and 1 day-lag concentration of SO(2) increased every 10 ug/m(3), the non-accidental mortality and the cardiovascular mortality at the six cities scale raised 0.40% (95% CI: 0.13%-0.67%) and 0.48% (95% CI: 0.11%-0.85%) respectively. When the day concentration of NO2 increased every 10 ug/m(3), the non-accidental mortality in Beijing, Tianjin, Shanghai, Guangzhou and Wuhan raised 0.60% (95% CI: 0.26%-0.95%), 0.96% (95% CI: 0.29% 1.64%), 0.43% (95% CI: 0.09%-0.78%), 1.17%(95%CI: 0.69%-1.66%) and 1.23%(95%CI: 0.19%-2.28%) respectively; the cardiovascular mortality in Beijing, Tianjin, Xi'an, Guangzhou and Wuhan raised 0.83% (95% CI: 0.34%-1.32%), 1.09% (95% CI: 0.25%-1.94%), 1.98% (95% CI: 0.00%-4.01%), 1.52% (95% CI: 0.70%-2.36%) and 2.04% (95% CI: 0.54%-3.56%) respectively. When the 1 day-lag concentration of NO(2) increased every 10 ug/m(3), the non-accidental mortality in Guangzhou and Wuhan raised 0.97% (95% CI: 0.49%-1.46%) and 1.67% (95% CI: 0.66%-2.70%)respectively; the cardiovascular mortality in Guangzhou and Wuhan raised 1.06% (95% CI: 0.24% 1.89%)and 2.42% (95% CI: 0.97%-3.89%) respectively. When the day and 1 day-lag concentration of NO(2) increased every 10 ug/m(3), the non-accidental mortality and the cardiovascular mortality at the six cities scale raised 0.81% (95% CI: 0.35%-1.28%), 1.03% (95% CI: 0.40%-1.66%) respectively. CONCLUSION: Exposure to SO(2) and NO(2) was significantly associated with daily non-accidental morality and cardiovascular morality at the multi-city scale in China. PMID- 26887305 TI - [Impact of dynamic changes of waist circumference and body mass index on type 2 diabetes mellitus risk]. AB - OBJECTIVE: To investigate the impact of dynamic change of waist circumference or body mass index (BMI) on type 2 diabetes mellitus (T2DM) populations in a cohort study. METHODS: We not only obtained the baseline survey data from program 'Prevention of Multiple Metabolic Disorders and metabolic syndrome (MS) in Jiangsu Province'(PMMJS) which started in 1994, and we conducted twice follow-ups from January 2002 to August 2003, and March 2006 to November 2007. After excluding subjects who were found to have T2DM at baseline, cardiovascular disease(CVD), and BMI<18.5 kg/m(2) , and loss to follow up because of relocation, death or other reasons, a total of 3 461 subjects were included in this analysis. They received investigation including questionnaires investigation, measurement and laboratory examination. The differences of gender, smoking, alcohol drinking and T2DM family history in different groups were examined using chi(2)-test, median and inter-quartile range were calculated for TG, and they were examined by rank test. Four equal parts of the differences of waist circumference and BMI were carried out in the COX regression model, to investigate the association between 2 years change of waist circumference or BMI and incidence of T2DM. We also examined the association between BMI and waist circumference modification and incident risk of T2DM in subjects with normal baseline BMI, baseline obese subjects, subjects with normal baseline waist circumference and baseline abdominal obese subjects. RESULTS: A total of 3 461 participants (1 406 males, 2 055 females) were investigated, including 160 new T2DM cases (60 males, 100 females) who were from between baseline and the second following up. The accumulative incidence was 4.6% (60/3 461). Multivariate COX regression model analysis results showed that the T2DM risk was relatively high in the highest quartile of waist circumference D-value group(HR=2.06, 95% CI: 1.27-3.16), the T2DM risk was also high in the highest quartile of BMI D-value group (HR=1.30, 95% CI: 0.86-1.95). In subjects with abdominal obesity and normal waist circumference at baseline, the incidence rate of T2DM in non-control group was 7.1% (40/565) , 6.3% (45/645), higher than that in control group (3.4%(71/2 096), 4.5%(4/155)) (chi(2) values were 3.98 and 15.18, P values were 0.043 and <0.001). In subjects with normal waist circumference, T2DM risk was higher in non-control group than that in control group (HR=2.12, 95% CI: 1.40-3.22). In abdominal obese subjects, T2DM risk was also higher in non-control group than that in control group (HR=1.14, 95% CI: 1.04-1.92). If waist circumference was not controlled, T2DM risk was high, no matter BMI controlled or not (HR(95% CI) were 1.73(1.17 2.54), 2.45(1.63-3.69) respectively). CONCLUSION: Controlling the waistline could reduce the risk of diabetes, and once waist circumference was not controlled, T2DM risk would be increased no matter BMI was controlled or not. PMID- 26887306 TI - [Impact of health educators' intervention on non-communicable diseases-related knowledge, attitude and behavior among rural residents]. AB - OBJECTIVE: To evaluate the impact of health educators' intervention on knowledge, attitude and behavior among rural residents and the feasibility of this intervention mode. METHODS: Using stratified cluster random sampling method, three towns and five villages in Yongchuan district, Chongqing municipality were selected from February to November, 2013. One or two health educators from each village were recruited by recommendation or voluntary registration. A total of 30 health educators were recruited and trained. Health educators who passed the exam of the training conducted the intervention and training of knowledge and skill about non-communicable disease (NCD) prevention and control for over 30 rural residents who lived nearby aged over 18 years old, could take care of themselves and complete questionnaire independently. 900 residents were selected as the study samples before and after the intervention. Questionnaire surveys were conducted before and after the intervention to evaluate the effect. Changes of knowledge and behavior among participants were compared by Chi-square test. Changes of attitude towards NCD prevention and control among participants were compared by two independent t-test. RESULTS: Before and after the intervention, the cognition rate about diagnostic criteria of hypertension among rural adults was 29.8% (268/900) and 67.9% (611/900), respectively(chi(2)=261.58, P<0.001). The cognition rate about risk factors of hypertension was 22.9% (206/900) and 78.2% (704/900), respectively(chi(2)=551.19, P<0.001). The cognition rate about the prevention measure of hypertension was 37.2% (335/900) and 88.0% (792/900) , respectively(chi(2)=495.64, P<0.001). The cognition rate about complications of hypertension was 15.4% (139/900) and 68.9% (620/900), respectively(chi(2)=527.07, P<0.001). The cognition rate about diagnostic criteria of diabetes was 12.9% (116/900) and 50.3% (453/900), respectively(chi(2)=291.85, P<0.001). The cognition rate about the criteria of risk population of diabetes was 8.6% (77/900) and 62.0% (558/900), respectively(chi(2)=562.94, P<0.001). The cognition rate about the symptom of diabetes was 29.8% (268/900) and 83.3% (750/900), respectively(chi(2)=525.31, P<0.001). The cognition about the preventive measure of diabetes was 44.7% (402/900) and 89.3% (804/900), respectively(chi(2)=406.06, P<0.001). The cognition rate about 6 g salt intake per person per day among rural adults was 28.0% (252/900) and 84.3% (759/900), respectively(chi(2)=580.04, P<0.001). The cognition about 25 g oil intake per person per day among rural adults was 26.7% (240/900) and 71.4% (643/900), respectively(chi(2)=361.04, P<0.001). The cognition about self-perception of body weight among rural adults was 62.9% (566/900) and 91.9% (827/900), respectively (chi(2)=216.28, P<0.001). The cognition about self-circumference among rural adult was 54.8% (493/900) and 87.7% (789/900), respectively(chi(2)=237.49, P<0.001). The cognition rate of self blood pressure was 60.5% (544/900) and 70.4% (634/900), respectively(chi(2)=14.92, P<0.001). Before and after the intervention, the scores of the necessity about conducting health education for the public among rural adults was (3.1+/-0.9 ) and (3.7+/-0.5 ), respectively(t=20.09, P<0.001). The score of the necessity about unhealthy lifestyle change among rural adults was (3.0+/-0.9 ) and (3.7+/-0.6), respectively(t=20.84, P<0.001). The score of the necessity about testing blood pressure and blood glucose regularly among rural adults was (3.0+/-0.9) and (3.7+/-0.6), respectively(t=21.07, P<0.001). The score of the necessity about body weight control was (2.9+/-1.0) and (3.6+/- 0.8), respectively(t=20.04, P<0.001). The score of the necessity about conducting hypertension screen among high risk population was (3.0+/-0.9) and (3.7+/-0.5), respectively(t=22.99, P<0.001). The score of the necessity about conducting diabetes screen among high risk population was (3.0 +/- 0.9) and (3.7 +/- 0.5), respectively(t=23.22, P<0.001). The score of the necessity about providing instruction service of diet and physical activity for high risk population was (3.0+/-0.9) and (3.7+/-0.5), respectively(t=22.41 and 22.87, P< 0.001). Before and after the intervention, the proportion of rural adults seeking counseling service about NCD was 44.0% (396/900) and 64.9% (584/900), respectively(chi(2)=79.17, P<0.001). The proportion of rural adults testing blood pressure in the recent six months was 43.4% (391/900) and 63.1% (568/900), respectively(chi(2)=69.92, P<0.001). The proportion of rural adults who tested blood glucose in the recent six months was 28.6%(257/900) and 48.1% (433/900), respectively(chi(2)=72.80,P<0.001). The proportion of rural adults who controlled body weight consciously was 34.7%(312/900) and 29.3% (264/900), respectively(chi(2)= 5.88,P<0.05). CONCLUSION: Health educators' intervention could raise rural participants' awareness and confidence about NCD significantly, but this intervention mode might have little impact on healthy behaviors change in a short time. PMID- 26887307 TI - [Effect evaluation on physical activities intervention of Hangzhou community medical staff as well as the factor analysis]. PMID- 26887308 TI - [The prevalence of overweight and obesity among aged 20-69 years old in Hubei province]. PMID- 26887309 TI - [Immunological surrogate endpoints to evaluate vaccine efficacy]. AB - An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID- 26887310 TI - [Development and application of adverse outcome pathway in toxicology research]. AB - Adverse outcome pathway (AOP) was a conceptual construct that integrated existing knowledge concerning the pathway of causal linkages between a molecular initiating event (MIE) and a final adverse effect at individual or population levels. The AOP methodology could be used as a basis for effects extrapolation and was an approach towards providing a framework for collecting and evaluating relevant chemical, biological and toxicological information. The framework would play an important role in risk assessment. We reviewed the concept of AOP, the development and assessment of the framework and the established models in toxicology researches. And the prospects and challenges of its application in toxicology were also introduced. PMID- 26887311 TI - Impact of agriculture and land use on nitrate contamination in groundwater and running waters in central-west Poland. AB - Protected areas due to their long-term protection are expected to be characterized by good water quality. However, in catchments where arable fields dominate, the impact of agriculture on water pollution is still problematic. In Poland, recently, the fertilization level has decreased, mostly for economic reasons. However, this applies primarily to phosphorus and potassium. In order to evaluate the impact of agriculture on water quality in a protected area with a high proportion of arable fields in the aspect of level and type of fertilization, complex monitoring has been applied. The present study was carried out in Wielkopolska National Park and its buffer zone, which are protected under Natura 2000 as Special Areas of Conservation and Special Protection Areas. The aim of the study were (1) to assess the impact of agriculture, with special attention on fertilization, on groundwater, and running water quality and (2) to designate priority areas for implementing nitrogen reduction measures in special attention on protected areas. In our study, high nitrogen concentrations in groundwater and surface waters were detected in the agricultural catchments. The results demonstrate that in the watersheds dominated by arable fields, high nitrogen concentrations in groundwater were measured in comparison to forestry catchments, where high ammonium concentrations were observed. The highest nitrogen concentrations were noted in spring after winter freezing, with a small cover of vegetation, and in the areas with a high level of nitrogen application. In the studied areas, both in the park and its buffer zone, unfavorable N:P and N:K ratios in supplied nutrients were detected. Severe shortage of phosphorus and potassium in applied fertilizers is one of the major factors causing leaching of nitrogen due to limited possibilities of its consumption by plants. PMID- 26887312 TI - Poverty within watershed and environmentally protected areas: the case of the indigenous community in Peninsular Malaysia. AB - "Indigenous people" have been acknowledged as among the poorest and most socio economically and culturally marginalized all over the world. This paper explores the socio-economic status of the indigenous people and their poverty profile within watershed and environmentally protected areas in Peninsular Malaysia. The findings of the study indicate that the "indigenous community" is likely to be poor if they live in environmentally sensitive and unprotected areas as compared to families under the new resettlement scheme. Inadequate access to basic education and employment contributed significantly to their poor economic status. The findings further reveal that the indigenous community is facing difficulties in receiving access and support in terms of basic needs such as housing, education, economic livelihood, and other social infrastructure. Moreover, the regulatory structure for the management of watershed areas as well as the emphasis for commodity crops such as palm oil and natural rubber have indirectly contributed toward the poverty level of the indigenous people. PMID- 26887313 TI - Retraction Note to: Biomonitoring fallout (137)Cs in resident and migratory fishes collected along the southern coast of India and assessment of dose. PMID- 26887314 TI - Differential bleaching of corals based on El Nino type and intensity in the Andaman Sea, southeast Bay of Bengal. AB - The Andaman coral reef region experienced mass bleaching events during 1998 and 2010. The purpose of this study is to investigate the role of the El Nino in the coral reef bleaching events of the Andaman region. Both Nino 3.4 and 3 indices were examined to find out the relationship between the mass bleaching events and El Nino, and correlated with sea surface temperature (SST) anomalies in the Andaman Sea. The result shows that abnormal warming and mass bleaching events in the Andaman Sea were seen only during strong El Nino years of 1997-1998 and 2009 2010. The Andaman Sea SST was more elevated and associated with El Nino Modoki (central Pacific El Nino) than conventional El Nino (eastern Pacific El Nino) occurrences. It is suggested that the development of hot spot patterns around the Andaman Islands during May 1998 and April-May 2010 may be attributed to zonal shifts in the Walker circulation driven by El Nino during the corresponding period. PMID- 26887315 TI - Novel synthetic benzimidazole-derived oligosaccharide, M3BIM, prevents ex vivo platelet aggregation and in vivo thromboembolism. AB - BACKGROUND: Thrombus formation, a phenomenon primarily related to increased platelet activation, plays a key role in cardiovascular and cerebrovascular diseases. Although the established antiplatelet agents, such as aspirin and clopidogrel, have been shown to be beneficial in treating thromboembolic diseases, they have considerable limitations. Hence, the development of more effective and safe antithrombotic agents is necessary to satisfy a substantial unmet clinical need. In recent years, the favorable properties of imidazole related drugs have prompted medicinal chemists to synthesize numerous novel therapeutic agents. The chemical structure of the benzimidazole backbone has proven antiplatelet properties. Moreover, synthetic oligosaccharides have exhibited antiplatelet properties. Therefore, we developed a new aldo benzimidazole-derived oligosaccharide compound, M3BIM, for achieving a stronger antiplatelet effect than the drugs which are being used in clinical aspects. We investigated the effects of M3BIM on platelet activation ex vivo and its antithrombotic activity in vivo. RESULTS: M3BIM (10-50 MUM) exhibited a more potent activity in inhibiting platelet aggregation stimulated by collagen than it did in inhibiting that stimulated by thrombin in washed human platelets. The M3BIM treatment revealed no cytotoxicity in zebrafish embryos, even at the highest concentration of 100 MUM. In addition, M3BIM inhibited the phosphorylation of phospholipase Cgamma2, protein kinase C (PKC), and mitogen activated protein kinases (MAPKs; extracellular signal-regulated kinase 2 and c Jun N-terminal kinase 1), and markedly reduced the ATP-release reaction and intracellular calcium mobilization in collagen-activated platelets. By contrast, M3BIM showed no effects on either collagen-induced p38 MAPK and Akt phosphorylation or phorbol 12, 13-dibutyrate-induced PKC activation and platelet aggregation. Moreover, the M3BIM treatment substantially prolonged the closure time in human whole blood, and increased the occlusion time in mesenteric microvessels and attenuated cerebral infarction in mice. For the study of anticoagulant activities, M3BIM showed no significant effects in the prolongation of activated partial thromboplastin time and prothrombin time in mice. CONCLUSION: The findings of our study suggest that M3BIM is a potential therapeutic agent for preventing or treating thromboembolic disorders. PMID- 26887317 TI - Canine Trichomonas tenax mandibular gland infestation. AB - BACKGROUND: Several species of trichomonads are intestinal or urogenital parasites of humans and animals, with only a few species typically being located in the oral cavity. The prevalence of oral trichomoniasis in dogs is approximately 15-25 %, although the prevalence varies among different populations and depends on age, sex and the health of the oral cavity. CASE PRESENTATION: A case of mandibular gland infestation by trichomonads in a 13-year-old female Dachshund with advanced periodontal disease and oral trichomoniasis is reported. The dog was referred due to a history of a painless swelling over the left submandibular region that increased in size over time. Based on physical and ultrasound examinations, a final diagnosis of mandibular gland cyst was established and transcutaneous needle aspiration was carried out. Numerous mobile trophozoites of trichomonads were found by microscopy and culturing for trichomonas was performed. The species was finally characterized as Trichomonas tenax by polymerase chain reaction and sequencing. CONCLUSIONS: Studies have shown that T. tenax can be found in humans in atypical locations such as the salivary glands and upper and lower respiratory tracts. According to our knowledge this is the first report of T. tenax being present in the salivary glands of a dog. Because of the relatively high prevalence of trichomoniasis in dogs with periodontal diseases, these parasites should be considered together with bacterial and viral agents in salivary gland infections, especially in individuals with compromised oral health. PMID- 26887318 TI - Screening of antitubercular compound library identifies novel shikimate kinase inhibitors of Mycobacterium tuberculosis. AB - Shikimate kinase of Mycobacterium tuberculosis is involved in the biosynthesis of aromatic amino acids through shikimate pathway. The enzyme is essential for the survival of M. tuberculosis and is absent from mammals, thus providing an excellent opportunity for identifying new chemical entities to combat tuberculosis with a novel mechanism of action. In this study, an antitubercular library of 1000 compounds was screened against M. tuberculosis shikimate kinase (MtSK). This effort led to the identification of 20 inhibitors, among which five promising leads exhibited half maximal inhibitory concentration (IC50) values below 10 MUM. The most potent inhibitor ("5631296") showed an IC50 value of 5.10 MUM +/- 0.6. The leads were further evaluated for the activity against multidrug resistant (MDR)-TB, Gram-positive and Gram-negative bacterial strains, mode of action, docking simulations, and combinatorial study with three frontline anti-TB drugs. Compound "5491210" displayed a nearly synergistic activity with rifampicin, isoniazid, and ethambutol while compound "5631296" was synergistic with rifampicin. In vitro cytotoxicity against HepG2 cell line was evaluated and barring one compound; all were found to be non-toxic (SI > 10). In order to rule out mitochondrial toxicity, the promising inhibitors were also evaluated for cell cytotoxicity using galactose medium where compounds "5631296" and "5122752" appeared non-toxic. Upon comprehensive analysis, compound "5631296" was found to be the most promising MtSK inhibitor that was safe, synergistic with rifampicin, and bactericidal against M. tuberculosis. PMID- 26887316 TI - 4-Hydroxyisoleucine attenuates the inflammation-mediated insulin resistance by the activation of AMPK and suppression of SOCS-3 coimmunoprecipitation with both the IR-beta subunit as well as IRS-1. AB - It is known that 4-hydroxyisoleucine (4-HIL) from seeds of Trigonella foenum graecum has beneficial effects on low-grade inflammation; therefore, the insulin signaling as well as the anti-inflammatory effects of 4-HIL in TNF-alpha-induced insulin resistance in C2C12 myotubes was studied with an aim to dissect out the mechanism(s) of the inflammation-mediated insulin resistance. TNF-alpha suppressed insulin-stimulated glucose transport rate and increased Ser-307 phosphorylation of insulin receptor substrate-1 (IRS-1). However, the treatment of 4-hydroxyisoleucine enhanced insulin-stimulated glucose transport rate via the activation of AMP-activated protein kinase (AMPK) in a dose-dependent manner. 4 HIL also increases the tyrosine phosphorylation of both IR-beta and IRS-1. Moreover, coimmunoprecipitation (Co-IP) of insulin receptor-beta (IR-beta) subunit with IRS-1 was found to be increased by 4-hydroxyisoleucine. Concentration of SOCS-3 protein and coimmunoprecipitation of SOCS-3 protein with both the IR-beta subunit as well as IRS-1 was found to be decreased by 4-HIL. We conclude that the 4-hydroxyisoleucine reverses the insulin resistance by the activation of AMPK and suppression of SOCS-3 coimmunoprecipitation with both the IR-beta subunit as well as IRS-1. PMID- 26887319 TI - New tools for chloroplast genetic engineering allow the synthesis of human growth hormone in the green alga Chlamydomonas reinhardtii. AB - In recent years, there has been an increasing interest in the exploitation of microalgae in industrial biotechnology. Potentially, these phototrophic eukaryotes could be used for the low-cost synthesis of valuable recombinant products such as bioactive metabolites and therapeutic proteins. The algal chloroplast in particular represents an attractive target for such genetic engineering, both because it houses major metabolic pathways and because foreign genes can be targeted to specific loci within the chloroplast genome, resulting in high-level, stable expression. However, routine methods for chloroplast genetic engineering are currently available only for one species-Chlamydomonas reinhardtii-and even here, there are limitations to the existing technology, including the need for an expensive biolistic device for DNA delivery, the lack of robust expression vectors, and the undesirable use of antibiotic resistance markers. Here, we describe a new strain and vectors for targeted insertion of transgenes into a neutral chloroplast locus that (i) allow scar-less fusion of a transgenic coding sequence to the promoter/5'UTR element of the highly expressed endogenous genes psaA or atpA, (ii) employ the endogenous gene psbH as an effective but benign selectable marker, and (iii) ensure the successful integration of the transgene construct in all transformant lines. Transformation is achieved by a simple and cheap method of agitation of a DNA/cell suspension with glass beads, with selection based on the phototrophic rescue of a cell wall deficient DeltapsbH strain. We demonstrate the utility of these tools in the creation of a transgenic line that produces high levels of functional human growth hormone. PMID- 26887320 TI - Biophotography: concepts, applications and perspectives. AB - Synthetic biology aims at manipulating biological systems by rationally designed and genetically introduced components. Efforts in photoactuator engineering resulted in microorganisms reacting to extracellular light-cues with various cellular responses. Some of them lead to the formation of macroscopically observable outputs, which can be used to generate images made of living matter. Several methods have been developed to convert colorless compounds into visible pigments by an enzymatic conversion. This has been exploited as a showcase for successful creation of an optogenetic tool; examples for basic light-controlled biological processes that have been coupled to this biophotography comprise regulation of transcription, protein stability, and second messenger synthesis. Moreover, biological reproduction of images is used as means to facilitate quantitative characterization of optogenetic switches as well as a technique to investigate complex cellular signaling circuits. Here, we will compare the different techniques for biological image generation, introduce experimental approaches, and provide future-perspectives for biophotography. PMID- 26887321 TI - An evaluation of a multi-component adult weight management on referral intervention in a community setting. AB - BACKGROUND: National Institute for Health and Care Excellence (NICE) guidance on adult weight management recommends interventions are multi-component. We aimed to assess the implementation and health benefits of a primary care referral to an adult multi-component weight management intervention in a community setting. The intervention was offered through Primary care in National Health Service (NHS) South Gloucestershire, UK, from Oct 2008 to Nov 2010, in partnership with statutory, community and commercial providers. The scheme offered 12 weeks' community based concurrent support of dietary (Weight Watchers, WW), physical activity (Exercise on Prescription, EOP) and behavioural change (motivational interviewing) components to obese adults. Funding was available for 600 places. RESULTS: Five hundred and fifty nine participants engaged with the intervention, mean age 48 years, 88% female. Mean weight loss for all engagers was 3.7 kg (95 % confidence interval 3.4, 4.1). Participants completing the intervention achieved the largest weight reduction (mean loss 5.9 kg; 5.3, 6.6). Achievement of 5% weight loss was higher in completers (58%; 50, 65) compared to non-completers (19%; 12, 26) and people who only participated in one commercial component of the intervention (either WW or EOP; 19%; 13, 24). CONCLUSION: A multi-component weight management programme may be beneficial for weight loss, but a randomized controlled trial is needed to establish effectiveness and to evaluate cost. PMID- 26887324 TI - Genotyping of Acanthamoeba spp. and characterization of the prevalent T4 type along with T10 and unassigned genotypes from amoebic keratitis patients in India. AB - Free-living amoebae of the genus Acanthamoeba are the causative agents of severe sight-threatening infection of the cornea. This study was designed to characterize the genotype of 20 Acanthamoeba spp. isolates obtained from corneal scrapings of 183 suspected Acanthamoeba keratitis patients reporting to the Outpatient Department/Casualty Services of Dr R. P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India during the period 2011-2015. Corneal scrapings were inoculated onto 2 % non-nutrient agar plates overlaid with Escherichia coli and incubated at 30 degrees C for 15 days. Amongst 183 suspected Acanthamoeba keratitis patients, 29 were found culture positive for Acanthamoeba spp. out of which 20 samples were established in axenic culture for molecular analysis. DNA was isolated and PCR assay was performed for the amplification of the diagnostic fragment 3 (DF3) (~280 bp) region of the 18S rRNA gene from axenic culture of 20 Acanthamoeba spp. isolates. Rns genotyping was performed on the basis of variation in nucleotide sequences of the DF3 region of the 18S rRNA gene. In the phylogenetic analysis, 16 of the 20 isolates were found to be of prevalent genotype T4, two were of genotype T10 and the remaining two isolates were of unassigned genotypes. Hence, it was concluded that genotype T4 was found as the most predominant genotype involved in Acanthamoeba keratitis infections. Genotype T10, which had not been reported from India, was detected for the first time in two patients. Two isolates were found to be unique, which shared < 95 % homology with all the known genotypes (T1-T20) of Acanthamoeba spp. PMID- 26887322 TI - CSF complement 3 and factor H are staging biomarkers in Alzheimer's disease. AB - INTRODUCTION: CSF levels of established Alzheimer's disease (AD) biomarkers remain stable despite disease progression, and non-amyloid non-tau biomarkers have the potential of informing disease stage and progression. We previously identified complement 3 (C3) to be decreased in AD dementia, but this change was not found by others in earlier AD stages. We hypothesized that levels of C3 and associated factor H (FH) can potentially distinguish between mild cognitive impairment (MCI) and dementia stages of AD, but we also found their levels to be influenced by age and disease status. RESULTS: We developed a biochemical/bioinformatics pipeline to optimize the handling of complex interactions between variables in validating biochemical markers of disease. We used data from the Alzheimer's Disease Neuro-imaging Initiative (ADNI, n = 230) to build parallel machine learning models, and objectively tested the models in a test cohort (n = 73) of MCI and mild AD patients independently recruited from Emory University. Whereas models incorporating age, gender, APOE epsilon4 status, and CSF amyloid and tau levels failed to reliably distinguish between MCI and mild AD in ADNI, introduction of CSF C3 and FH levels reproducibly improved the distinction between the two AD stages in ADNI (p < 0.05) and the Emory cohort (p = 0.014). Within each AD stage, the final model also distinguished between fast vs. slower decliners (p < 0.001 for MCI, p = 0.007 for mild AD), with lower C3 and FH levels associated with more advanced disease and faster progression. CONCLUSIONS: We propose that CSF C3 and FH alterations may reflect stage associated biomarker changes in AD, and can complement clinician diagnosis in diagnosing and staging AD using the publically available ADNI database as reference. PMID- 26887323 TI - A systematic review of correlates of sedentary behaviour in adults aged 18-65 years: a socio-ecological approach. AB - BACKGROUND: Recent research shows that sedentary behaviour is associated with adverse cardio-metabolic consequences even among those considered sufficiently physically active. In order to successfully develop interventions to address this unhealthy behaviour, factors that influence sedentariness need to be identified and fully understood. The aim of this review is to identify individual, social, environmental, and policy-related determinants or correlates of sedentary behaviours among adults aged 18-65 years. METHODS: PubMed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between January 2000 and September 2015. The search strategy was based on four key elements and their synonyms: (a) sedentary behaviour (b) correlates (c) types of sedentary behaviours (d) types of correlates. Articles were included if information relating to sedentary behaviour in adults (18-65 years) was reported. Studies on samples selected by disease were excluded. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42014009823). RESULTS: 74 original studies were identified out of 4041: 71 observational, two qualitative and one experimental study. Sedentary behaviour was primarily measured as self-reported screen leisure time and total sitting time. In 15 studies, objectively measured total sedentary time was reported: accelerometry (n = 14) and heart rate (n = 1). Individual level factors such as age, physical activity levels, body mass index, socio economic status and mood were all significantly correlated with sedentariness. A trend towards increased amounts of leisure screen time was identified in those married or cohabiting while having children resulted in less total sitting time. Several environmental correlates were identified including proximity of green space, neighbourhood walkability and safety and weather. CONCLUSIONS: Results provide further evidence relating to several already recognised individual level factors and preliminary evidence relating to social and environmental factors that should be further investigated. Most studies relied upon cross-sectional design limiting causal inference and the heterogeneity of the sedentary measures prevented direct comparison of findings. Future research necessitates longitudinal study designs, exploration of policy-related factors, further exploration of environmental factors, analysis of inter-relationships between identified factors and better classification of sedentary behaviour domains. PMID- 26887325 TI - Antiepileptogenic effects of borneol in pentylenetetrazole-induced kindling in mice. AB - Borneol, a bicyclic monoterpene, can easily cross the blood brain barrier and was found to possess gamma amino butyric acid (GABA) modulatory effect. The present study was aimed at investigating the antiepileptogenic effect of borneol in the pentylenetetrazole (PTZ)-induced kindling besides its ability to suppress oxidative stress and neuroinflammatory marker, glial fibrillary acidic protein (GFAP). Repeated administration of a subconvulsive dose of PTZ (35 mg/kg, i.p.) on every alternate day for 4 weeks produced kindling in mice. Borneol (5, 10, and 25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) were given as a pretreatment prior to each PTZ injection during the progression of kindling. Oxidative stress parameters such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and lipid peroxidation (LPO) were assessed at the end of the study. Neuronal damage was assessed by hematoxylin and eosin staining technique. GFAP was also evaluated in the hippocampus region of the brain by using immunohistochemistry. Borneol significantly suppressed the process of epileptogenesis in PTZ-kindled mice. The biochemical alterations induced by PTZ kindling were ameliorated in borneol-treated animals which was indicated by decreased LPO and increased SOD, GSH, CAT levels. The distinct neuronal damage observed in the kindled group was counteracted by borneol. Furthermore, it decreased the levels of GFAP which was manifested by reduced immunostaining. The above results are suggestive of the antiepileptogenic potential of borneol in the PTZ-induced kindling model of epilepsy, and thus, it could be a prospective molecule in the treatment of epilepsy. PMID- 26887326 TI - Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice. AB - BACKGROUND: Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice. METHODS: Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1-14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-kappaB (NF-kappaB) in the hippocampus were also examined. RESULTS: Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-kappaB pathway (i.e., phosphorylation of p65) in the hippocampus. CONCLUSION: These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-kappaB signaling in the hippocampus. PMID- 26887328 TI - Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds. AB - Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-beta-D-glucopyranosyl oleanolic acid 3-O-beta-D-glucopyranosyl (1->3)-beta-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-beta-D-glucopyranosyl (1->3)-beta-D glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887327 TI - Exercise training improves vascular function in adolescents with type 2 diabetes. AB - The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro- and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13-21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym-based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow-mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual-energy X-ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic-hyperinsulinemic clamp protocol, cardiorespiratory fitness (VO2peak), and muscular strength (1RM). Exercise training increased FMD (P < 0.05), microvascular function (P < 0.05), total lean mass (P < 0.05), and muscle strength (P < 0.001). There were no changes in cardiorespiratory fitness, body weight, BMI, or M. In the control group, body weight (P < 0.01), BMI (P < 0.01), and total fat mass (P < 0.05) increased. At week 24, improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes. PMID- 26887329 TI - Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections. AB - PURPOSE: A 2012 report and subsequent case series described anti-N-methyl-D aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. MATERIALS AND METHODS: We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. RESULTS: In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. CONCLUSIONS: In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies. PMID- 26887330 TI - A novel rodent model of severe renal ischemia reperfusion injury. AB - Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of ~50%. Histology revealed short- and long term disruption of renal architecture. Despite the injury severity, post operative animal losses are <5%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules. PMID- 26887331 TI - Transport of 3-fluoro-L-alpha-methyl-tyrosine (FAMT) by organic ion transporters explains renal background in [(18)F]FAMT positron emission tomography. AB - A PET tracer for tumor imaging, 3-(18)F-l-alpha-methyl-tyrosine ([(18)F]FAMT), has advantages of high cancer-specificity and low physiological background. In clinical studies, FAMT-PET has been proved useful for the detection of malignant tumors and their differentiation from inflammation and benign lesions. The tumor specific uptake of FAMT is due to its high-selectivity to cancer-type amino acid transporter LAT1 among amino acid transporters. In [(18)F]FAMT PET, kidney is the only organ that shows high physiological background. To reveal transporters involved in renal accumulation of FAMT, we have examined [(14)C]FAMT uptake on the organic ion transporters responsible for the uptake into tubular epithelial cells. We have found that OAT1, OAT10 and OCTN2 transport [(14)C]FAMT. The [(14)C]FAMT uptake was inhibited by probenecid, furosemide and ethacrynic acid, consistent with the properties of the transporters. The amino acid uptake inhibitor, 2-amino-2-norbornanecarboxylic acid (BCH), also inhibited the [(14)C]FAMT uptake, whereas OCTN2-mediated [(14)C]FAMT uptake was Na(+) dependent. We propose that FAMT uptake by OAT1, OAT10 and OCTN2 into tubular epithelial cells could contribute to the renal accumulation of FAMT. The results from this study would provide clues to the treatments to reduce renal background and enhance tumor uptake as well as to designing PET tracers with less renal accumulation. PMID- 26887332 TI - Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model. AB - We previously reported that camostat mesilate (CM) had renoprotective and antihypertensive effects in rat CKD models. In this study, we examined if CM has a distinct renoprotective effect from telmisartan (TE), a renin-angiotensin aldosterone system (RAS) inhibitor, on the progression of CKD. We evaluated the effect of CM (400 mg/kg/day) and/or TE (10 mg/kg/day) on renal function, oxidative stress, renal fibrosis, and RAS components in the adenine-induced rat CKD model following 5-weeks treatment period. The combination therapy with CM and TE significantly decreased the adenine-induced increase in serum creatinine levels compared with each monotherapy, although all treatment groups showed similar reduction in blood pressure. Similarly, adenine-induced elevation in oxidative stress markers and renal fibrosis markers were significantly reduced by the combination therapy relative to each monotherapy. Furthermore, the effect of the combination therapy on plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was similar to that of TE monotherapy, and CM had no effect on both PRA and PAC, suggesting that CM has a distinct pharmacological property from RAS inhibition. Our findings indicate that CM could be a candidate drug for an add-on therapy for CKD patients who had been treated with RAS inhibitors. PMID- 26887333 TI - Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait. AB - BACKGROUND: Gait and akinesia deterioration in PD patients during the immediate postoperative period of DBS has been directly related to stimulation in the subthalamic region. The underlying mechanisms remain poorly understood. The aim of the present study was to clinically and anatomically describe this side effect. METHODS: PD patients presenting with a worsening of gait and/or akinesia following STN-DBS, that was reversible on stimulation arrest were included. The evaluation included (1) a Stand Walk Sit Test during a monopolar survey of each electrode in the on-drug condition; (2) a 5-condition test with the following conditions: off-drug/off-DBS, off-drug/on-best-compromise-DBS, on-drug/off-DBS, on-drug/on-best-compromise-DBS, and on-drug/on-worsening-DBS, which utilized the contact inducing the most prominent gait deterioration. The following scales were performed: UPDRSIII subscores, Stand Walk Sit Test, and dyskinesia and freezing of gait scales. Localization of contacts was performed using a coregistration method. RESULTS: Twelve of 17 patients underwent the complete evaluation. Stimulation of the most proximal contacts significantly slowed down the Stand Walk Sit Test. The on-drug/on-worsening-DBS condition compared with the on drug/off-DBS condition worsened akinesia (P = 0.02), Stand Walk Sit Test (P = 0.001), freezing of gait (P = 0.02), and improved dyskinesias (P = 0.003). Compared with the off-drug/off-DBS condition, the on-drug/on-worsening-DBS condition improved rigidity (P = 0.007) and tremor (P = 0.007). Worsening contact sites were predominantly dorsal and anterior to the STN in the anterior zona incerta and Forel fields H2. CONCLUSIONS: A paradoxical deterioration of gait and akinesia is a rare side effect following STN-DBS. We propose that this may be related to misplaced contacts, and we discuss the pathophysiology and strategies to identify and manage this complication. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26887334 TI - Erratum to: 'Phosphoproteomic analysis reveals Smarcb1 dependent EGFR signaling in Malignant Rhabdoid tumor cells'. PMID- 26887335 TI - Privacy and Confidentiality Practices In Adolescent Family Planning Care At Federally Qualified Health Centers. AB - CONTEXT: The confidentiality of family planning services remains a high priority to adolescents, but barriers to implementing confidentiality and privacy practices exist in settings designed for teenagers who are medically underserved, including federally qualified health centers (FQHCs). METHODS: A sample of 423 FQHCs surveyed in 2011 provided information on their use of five selected privacy and confidentiality practices, which were examined separately and combined into an index. Regression modeling was used to assess whether various state policies and organizational characteristics were associated with FQHCs' scores on the index. In-depth case studies of six FQHCs were conducted to provide additional contextual information. RESULTS: Among FQHCs reporting on confidentiality, most reported providing written or verbal information regarding adolescents' rights to confidential care (81%) and limiting access to family planning and medical records to protect adolescents' confidentiality (84%). Far fewer reported maintaining separate medical records for family planning (10%), using a security block on electronic medical records to prevent disclosures (43%) or using separate contact information for communications regarding family planning services (50%). Index scores were higher among FQHCs that received Title X funding than among those that did not (coefficient, 0.70) and among FQHCs with the largest patient volumes than among those with the smallest caseloads (0.43). Case studies highlighted how a lack of guidelines and providers' confusion over relevant laws present a challenge in offering confidential care to adolescents. CONCLUSIONS: The organizational practices used to ensure adolescent family planning confidentiality in FQHCs are varied across organizations. PMID- 26887336 TI - SKA2 methylation predicts reduced cortical thickness in prefrontal cortex. PMID- 26887337 TI - Increased expression of IDO associates with poor postoperative clinical outcome of patients with gastric adenocarcinoma. AB - Clinical significance of 2,3-dioxygenase (IDO) has been studied in types of tumors, but the role that IDO played in gastric adenocarcinoma (GAC) is still unclear. Here, we aim to investigate the prognostic value of IDO expression in patients with GAC. We examined intratumoral IDO expression in retrospectively enrolled 357 patients with GAC undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of IDO expression and its association with clinical pathological factors. We generated a predictive nomogram by integrating IDO expression with the TNM staging system for overall survival of GAC patients. High expression of intratumoral IDO predicted a dismal outcome. Intratumoral IDO expression gave a further discrimination for the prognosis of GAC patients. By Cox multivariate analysis, IDO expression was defined as an independent prognosticator. The generated nomogram performed well in predicting the 3- and 5-year overall survival of GAC patients. Conclusively, IDO is a potential prognostic biomarker for overall survival of patients with GAC after gastrectomy. PMID- 26887338 TI - Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis. AB - Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1. PMID- 26887339 TI - Relevance of Pre-Transplant alpha-fetoprotein Dynamics in Liver Transplantation for Hepatocellular Cancer. AB - BACKGROUND: The magnitude of pre-transplant a-fetoprotein (AFP) changes has been advocated to be a superior predictor of hepatocellular cancer (HCC) recurrence following liver transplantation. The aim of this study was to compare AFP dynamics and last pre-transplant AFP as risk factors for post-transplant HCC recurrence. MATERIAL AND METHODS: Data of 146 patients after liver transplantation for HCC were analyzed retrospectively. RESULTS: While last pre transplant AFP was a significant predictor of microvascular invasion (p=0.006) and poor tumor differentiation (p=0.020), AFP slope was associated only with microvascular invasion (p=0.029). Notably, last pre-transplant AFP (p<0.001), but not AFP slope (p=0.279), was an independent risk factor for recurrence. No significant effects of AFP slope were also found following division of patients into those with pre-transplant AFP <100 (p=0.260) and those with AFP >100 (p=0.178) ng/mL. Moreover, prediction of recurrence based on last pre-transplant AFP was superior (p=0.018) to those based on AFP slope. Recurrence-free survival at 5 years was superior in patients with pre-transplant AFP persistently at (97.3%) or dropping to <100 ng/mL (100.0%) as compared to patients with AFP rising to (75.0%) or persistently at >100 ng/mL (38.4%; p<0.001). CONCLUSIONS: The risk of post-transplant HCC recurrence is dependent on the last pre transplant AFP regardless of its previous dynamics. PMID- 26887340 TI - A Comparison of New Pharmacological Agents for the Treatment of Obesity. AB - OBJECTIVE: To review and compare the phase 3 clinical trial evidence on the 4 new pharmacological agents approved for the management of overweight and obesity. DATA SOURCES: Searches were performed (from 1966 through January 2016) in PubMed/MEDLINE, Scientific Citation Index, and product package inserts to identify key phase 3 clinical trials that were used in the approval of each agent. STUDY SELECTION AND DATA EXTRACTION: Phase 3 clinical trials that listed end points of >=5% and >=10% weight loss benchmarks from baseline as well as total percentage of weight loss by participants were selected for the review. DATA SYNTHESIS: No head-to-head trials have been identified between these agents at this point, which limits comparisons across agents. Phentermine/topiramate ER appeared to have the best overall average weight loss from baseline as well as highest percentages of patients achieving both >=5% and >=10% weight loss benchmarks, followed second by naltrexone/bupropion, and then liraglutide, with lorcaserin showing the lowest rates. Phentermine/topiramate ER completion rates were highest for both treatment and placebo groups, followed by liraglutide, with lorcaserin and naltrexone/bupropion showing similar completion rates, below that of the other 2 agents. Common side effects reported differed between agents, although the most common adverse events reported were gastrointestinal in nature, with liraglutide demonstrating the highest reported rates and lorcaserin demonstrating the lowest. CONCLUSION: These 4 new pharmacological agents represent new options for the clinician to utilize when trying to manage the problem of obesity. No clear first-line agent has emerged, so treatment decisions should be based on patient-specific factors. PMID- 26887341 TI - Antioxidant activity of a Lachnum YM226 melanin-iron complex and its influence on cytokine production in mice with iron deficiency anemia. AB - The present study aims to investigate the protective effects of an orally administered Lachnum YM226 melanin-iron complex (LM-Fe) against iron deficiency anemia (IDA) in mice. The IDA mouse model was established by feeding mice with iron-deficient food. Different doses of LM-Fe were given to the anaemic mice via intragastric administration, with FeCl3 and FeSO4 used as positive controls. After the iron supplement administration, it was observed that LM-Fe could significantly improve the decreased haemoglobin (Hb) level, and normalize the serum iron (SI) level, total iron-binding capacity (TIBC) and serum ferritin (SF) of the anaemic mice in a dose-dependent manner. In addition, treatment with LM-Fe significantly increased the antioxidant enzyme activities of superoxidase dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in plasma to normal or better. Furthermore, the levels of tumour necrosis factor-alpha (TNF alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were obviously decreased in the LM-Fe supplemented groups compared with the model group, while the level of interleukin-2 (IL-2) was significantly increased. In conclusion, LM Fe was efficient at ameliorating the anemia symptoms, improving the activities of antioxidant enzymes and adjusting the immune dysfunction of anaemic mice. Thus, these results demonstrated that LM-Fe might be exploited as an efficient and multifunctional iron supplement. PMID- 26887342 TI - Heteroscedastic transformation cure regression models. AB - Cure models have been applied to analyze clinical trials with cures and age-at onset studies with nonsusceptibility. Lu and Ying (On semiparametric transformation cure model. Biometrika 2004; 91:331?-343. DOI: 10.1093/biomet/91.2.331) developed a general class of semiparametric transformation cure models, which assumes that the failure times of uncured subjects, after an unknown monotone transformation, follow a regression model with homoscedastic residuals. However, it cannot deal with frequently encountered heteroscedasticity, which may result from dispersed ranges of failure time span among uncured subjects' strata. To tackle the phenomenon, this article presents semiparametric heteroscedastic transformation cure models. The cure status and the failure time of an uncured subject are fitted by a logistic regression model and a heteroscedastic transformation model, respectively. Unlike the approach of Lu and Ying, we derive score equations from the full likelihood for estimating the regression parameters in the proposed model. The similar martingale difference function to their proposal is used to estimate the infinite dimensional transformation function. Our proposed estimating approach is intuitively applicable and can be conveniently extended to other complicated models when the maximization of the likelihood may be too tedious to be implemented. We conduct simulation studies to validate large-sample properties of the proposed estimators and to compare with the approach of Lu and Ying via the relative efficiency. The estimating method and the two relevant goodness-of-fit graphical procedures are illustrated by using breast cancer data and melanoma data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887343 TI - Ceratonia siliqua L. hydroethanolic extract obtained by ultrasonication: antioxidant activity, phenolic compounds profile and effects in yogurts functionalized with their free and microencapsulated forms. AB - Bioactive extracts were obtained from powdered carob pulp through an ultrasound extraction process and then evaluated in terms of antioxidant activity. Ten minutes of ultrasonication at 375 Hz were the optimal conditions leading to an extract with the highest antioxidant effects. After its chemical characterization, which revealed the preponderance of gallotannins, the extract (free and microencapsulated) was incorporated in yogurts. The microspheres were prepared using an extract/sodium alginate ratio of 100/400 (mg mg(-1)) selected after testing different ratios. The yogurts with the free extract exhibited higher antioxidant activity than the samples added with the encapsulated extracts, showing the preserving role of alginate as a coating material. None of the forms significantly altered the yogurt's nutritional value. This study confirmed the efficiency of microencapsulation to stabilize functional ingredients in food matrices maintaining almost the structural integrity of polyphenols extracted from carob pulp and furthermore improving the antioxidant potency of the final product. PMID- 26887345 TI - Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection. AB - It is well known that occludin (OCLN) is involved in hepatitis C virus (HCV) entry into hepatocytes, but there has been no conclusive evidence that OCLN is essential for HCV infection. In this study, we first established an OCLN-knockout cell line derived from human hepatic Huh7.5.1-8 cells using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 system, in which two independent targeting plasmids expressing single-guide RNAs were used. One established cell clone, named OKH-4, had the OCLN gene truncated in the N-terminal region, and a complete defect of the OCLN protein was shown using immunoblot analysis. Infection of OKH-4 cells with various genotypes of HCV was abolished, and exogenous expression of the OCLN protein in OKH-4 cells completely reversed permissiveness to HCV infection. In addition, using a co culture system of HCV-infected Huh7.5.1-8 cells with OKH-4 cells, we showed that OCLN is also critical for cell-to-cell HCV transmission. Thus, we concluded that OCLN is essential for HCV infection of human hepatic cells. Further experiments using HCV genomic RNA-transfected OKH-4 cells or HCV subgenomic replicon harboring OKH-4 cells suggested that OCLN is mainly involved in the entry step of the HCV life cycle. It was also demonstrated that the second extracellular loop of OCLN, especially the two cysteine residues, is critical for HCV infection of hepatic cells. OKH-4 cells may be a useful tool for understanding not only the entire mechanism of HCV entry, but also the biological functions of OCLN. PMID- 26887344 TI - Proteomic Characterization Reveals That MMP-3 Correlates With Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Cell and Lung Transplantation. AB - Improved diagnostic methods are needed for bronchiolitis obliterans syndrome (BOS), a serious complication after allogeneic hematopoietic cell transplantation (HCT) and lung transplantation. For protein candidate discovery, we compared plasma pools from HCT transplantation recipients with BOS at onset (n = 12), pulmonary infection (n = 16), chronic graft-versus-host disease without pulmonary involvement (n = 15) and no chronic complications after HCT (n = 15). Pools were labeled with different tags (isobaric tags for relative and absolute quantification), and two software tools identified differentially expressed proteins (>=1.5-fold change). Candidate proteins were further selected using a six-step computational biology approach. The diagnostic value of the lead candidate, matrix metalloproteinase 3 (MMP3), was evaluated by enzyme-linked immunosorbent assay in plasma of a verification cohort (n = 112) with and without BOS following HCT (n = 76) or lung transplantation (n = 36). MMP3 plasma concentrations differed significantly between patients with and without BOS (area under the receiver operating characteristic curve 0.77). Consequently, MMP3 represents a potential noninvasive blood test for diagnosis of BOS. PMID- 26887346 TI - How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies. AB - Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer's disease (AD), including the superoxide anion radical (O2(.-))-scavenging activity, Abeta fibrils (fAbeta) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2(.-)-scavenging activity and stronger inhibition against fAbeta formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product. PMID- 26887347 TI - Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands. AB - Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia. PMID- 26887348 TI - The impact of KRAS mutations on prognosis in surgically resected colorectal cancer patients with liver and lung metastases: a retrospective analysis. AB - BACKGROUND: KRAS mutations are common in colorectal cancer (CRC). The role of KRAS mutation status as a prognostic factor remains controversial, and most large population-based cohorts usually consist of patients with non-metastatic CRC. We evaluated the impact of KRAS mutations on the time to recurrence (TTR) and overall survival (OS) in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy. METHODS: Patients who underwent curative resection for primary and synchronous metastases were retrospectively collected in a single institution during a 6 year period between January 2008 and June 2014. Patients with positive surgical margins, those with known BRAF mutation, or those with an unknown KRAS mutation status were excluded, and a total of 82 cases were identified. The pathological and clinical features were evaluated. Patients' outcome with KRAS mutation status for TTR and OS were investigated by univariate and multivariate analysis. RESULTS: KRAS mutations were identified in 37.8% of the patients and not associated with TTR or OS between KRAS wild type and KRAS mutation cohorts (log-rank p = 0.425 for TTR; log-rank p = 0.137 for OS). When patients were further subdivided into three groups according to mutation subtype (wild-type vs. KRAS codon 12 mutation vs. KRAS codon 13 mutation) or amino acid missense mutation type (G > A vs. G > T vs. G > C), there were no significant differences in TTR or OS. Mutational frequencies were significantly higher in patients with lung metastases compared with those with liver and ovary/bladder metastases (p = 0.039), however, KRAS mutation status was not associated with an increased risk of relapsed in the lung. CONCLUSIONS: KRAS mutation was not associated with TTR or OS in patients with metastatic CRC who underwent curative surgery with perioperative chemotherapy. PMID- 26887349 TI - Pregnancy outcomes in women with endometriosis: a national record linkage study. AB - OBJECTIVE: To determine pregnancy outcomes in women with endometriosis. DESIGN: A national population based cohort study using record linkage. SETTING: Scotland. PARTICIPANTS: A cohort of 14 655 women followed up over a 30-year period (1981 2010). METHODS: In a nationwide Scottish study, we compared pregnancy outcomes in 5375 women with surgically confirmed endometriosis with outcomes in 8710 women without endometriosis who were pregnant during the same time period. Data were analysed using univariable and multivariable logistic regression after adjusting for confounding factors. MAIN OUTCOME MEASURES: Outcome measures evaluated included miscarriage, ectopic pregnancy, stillbirths and other pregnancy complications such as hypertensive disorders of pregnancy, antepartum and postpartum haemorrhage, operative delivery and preterm births. The outcomes were presented as adjusted odds ratios (OR) with 95% confidence intervals (CI). RESULTS: On multivariable analysis, after adjusting for age, parity, socio economic status and year of delivery, women with endometriosis when compared to women without endometriosis, had a significantly higher risk of early pregnancy complications with adjusted OR (95% CI) of 1.76 (1.44, 2.15) and 2.70 (1.09, 6.72) for miscarriage and ectopic pregnancy, respectively. A previous diagnosis of endometriosis was associated with a significantly increased risk of [adjusted OR (95% CI)] placenta praevia [2.24 (1.52, 3.31)], unexplained antepartum haemorrhage [1.67 (1.39, 2.00)], postpartum haemorrhage [1.30 (1.61, 1.46)] and preterm births [1.26 (1.07, 1.49)] in pregnancies progressing beyond 24 weeks. CONCLUSION: Endometriosis predisposes women to an increased risk of early pregnancy loss and later pregnancy complications. TWEETABLE ABSTRACT: Endometriosis predisposes women to an increased risk of early pregnancy loss and later pregnancy complications. PMID- 26887350 TI - Obesity and Diabetes Mellitus Adversely Affect Outcomes after Cardiac Surgery in Children's Hospitals. AB - OBJECTIVE: To assess how obesity or diabetes mellitus impacts outcomes in patients undergoing cardiac surgery in pediatric hospitals. DESIGN: A multi institutional, matched case-control study of the Pediatric Health Information System database was performed. SETTING: Tertiary children's hospitals in the United States. PATIENTS: All cardiac surgical cases in patients with obesity or diabetes mellitus between 2004 and 2012 were included. Cases were matched to controls by age, sex, race, and Risk Adjustment for Congenital Heart Surgery score. OUTCOME MEASURES: Mortality, surgical complications, and hospital utilization. Differences in outcome measures were assessed by chi-square and Mann Whitney tests. P value < .05 was significant. RESULTS: Six hundred twenty-nine cardiac surgical cases (median age 17 years [IQR 12-32]) with obesity or diabetes mellitus were matched to 629 controls. Cases demonstrated lower median household income than those in the control group ($38,031 [IQR $31,900-$48,844] vs. ($41,896 [IQR $32,854-$56,020], P < .001). Mortality was similar between cases and controls (22% vs. 1.9%, P =.692). Surgical complications occurred similarly between cases and controls (13.5% vs. 12.4%, P = .535). Cases had longer intensive care unit length of stay than controls (3 vs. 2 days, P = .001), resulting in longer overall hospital length of stay (5 vs. 4 days, P < .001). Cases also had a higher odds of undergoing mechanical ventilation for >96 hours (OR 2.0, 95% CI 1.1-3.7) and higher rate of total parenteral nutrition use (7.2% vs. 4.5%, P = .040). Median hospital charges were higher in cases (clinical: $6,696 vs. $5,872; laboratory: $14,168 vs. $12,251; pharmacy: $12,971 vs. $10,426; imaging: $6,259 vs. $5,660; P <= .030 for all). CONCLUSIONS: The presence of obesity or diabetes mellitus was associated with increased postoperative morbidity, hospital utilization, and cost in patients undergoing cardiac surgery in pediatric hospitals. PMID- 26887351 TI - Recreational drug use and related social factors among HIV-positive men in Japan. AB - This study aims to determine the relationship between recreational drug use in HIV-positive males in the past year and socio-economic factors and/or social support networks in Japan. A national online survey in a cross-sectional study was conducted by HIV Futures Japan project from July 2013 to February 2014. Of the 1095 HIV-positive individuals who responded, 913 responses were determined to be valid; responses from the 875 males were analysed. A total of 282 participants used addictive drugs (32.2%) in past year. New psychoactive substances were used by 121 participants (13.8%), methamphetamine or amphetamine by 47 (5.4%), air dusters/sprays/gas by 31 (3.5%), 5-methoxy-N,N-diisopropyltryptamine (5MeO-DIPT) by 16 (1.8%) and cannabis (1.0%) by 9. Multiple logistic regression analysis was performed with the use of alkyl nitrites, addictive drugs, air dusters and thinners, which are low illegality, as dependent variables. We found that the odds ratio (95% confidence interval) for use among participants with full-time and temp/contracted/part-time employees compared to management/administration professions were 2.59 (0.99-6.77) and 2.61 (0.91-7.51). Also, a correlation was observed between alkyl nitrites and new psychoactive substances and usage rates in people engaged in few HIV-positive networks. It is necessary to develop targeted policies for drug use prevention and user support among HIV-positive men and to support and provide care for drug users who are isolated or have a narrow HIV/AIDS support network. PMID- 26887352 TI - Backdating of events in electronic primary health care data: should one censor at the date of last data collection. AB - PURPOSE: Studies using primary care databases often censor follow-up at the date data are last collected from clinical computer systems (last collection date (LCD)). We explored whether this results in the selective exclusion of events entered in the electronic health records after their date of occurrence, that is, backdated events. METHODS: We used data from The Health Improvement Network (THIN). Using two versions of the database, we identified events that were entered into a later (THIN14) but not an earlier version of the database (THIN13) and investigated how the number of entries changed as a function of time since LCD. Times between events and the dates they were recorded were plotted as a function of time since the LCD in an effort to determine appropriate points at which to censor follow-up. RESULTS: There were 356 million eligible events in THIN14 and 355 million eligible events in THIN13. When comparing the two data sets, the proportion of missing events in THIN13 was highest in the month prior to the LCD (9.6%), decreasing to 5.2% at 6 months and 3.4% at 12 months. The proportion of missing events was largest for events typically diagnosed in secondary care such as neoplasms (28% in the month prior to LCD) and negligible for events typically diagnosed in primary care such as respiratory events (2% in the month prior to LCD). CONCLUSIONS: Studies using primary care databases, particularly those investigating events typically diagnosed outside primary care, should censor follow-up prior to the LCD to avoid underestimation of event rates. PMID- 26887353 TI - Dynamics and plasticity of the epithelial to mesenchymal transition induced by miR-200 family inhibition. AB - Whereas miR-200 family is known to be involved in the epithelial-to-mesenchymal transition (EMT), a crucial biological process observed in normal and pathological contexts, it has been largely unclear how far the functional levels of these tiny RNAs alone can propagate the molecular events to accomplish this process within several days. By developing a potent inhibitor of miR-200 family members (TuD-141/200c), the expression of which is strictly regulatable by the Tet (tetracycline)-On system, we found using a human colorectal cell line, HCT116, that several direct gene target mRNAs (Zeb1/Zeb2, ESRP1, FN1and FHOD1) of miR-200 family were elevated with distinct kinetics. Prompt induction of the transcriptional suppressors, Zeb1/Zeb2 in turn reduced the expression levels of miR-200c/-141 locus, EpCAM, ESRP1 and E-Cad. The loss of ESRP1 subsequently switched the splicing isoforms of CD44 and p120 catenin mRNAs to mesenchymal type. Importantly, within 9 days after the release from the inhibition of miR-200 family, all of the expression changes in the 14 genes observed in this study returned to their original levels in the epithelial cells. This suggests that the inherent epithelial plasticity is supported by a weak retention of key regulatory gene expression in either the epithelial or mesenchymal states through epigenetic regulation. PMID- 26887354 TI - Effects of submaximal and supramaximal interval training on determinants of endurance performance in endurance athletes. AB - We compared the effects of submaximal and supramaximal cycling interval training on determinants of exercise performance in moderately endurance-trained men. Maximal oxygen consumption (VO2max ), peak power output (Ppeak ), and peak and mean anaerobic power were measured before and after 6 weeks (3 sessions/week) of submaximal (85% maximal aerobic power [MP], HIIT85 , n = 8) or supramaximal (115% MP, HIIT115 , n = 9) interval training to exhaustion in moderately endurance trained men. High-intensity training volume was 47% lower in HIIT115 vs HIIT85 (304 +/- 77 vs 571 +/- 200 min; P < 0.01). Exercise training was generally associated with increased VO2max (HIIT85 : +3.3 +/- 3.1 mL/kg/min; HIIT115 : +3.3 +/- 3.6 ml/kg/min; Time effect P = 0.002; Group effect: P = 0.95), Ppeak (HIIT85 : +18 +/- 9 W; HIIT115 : +16 +/- 27 W; Time effect P = 0.045; Group effect: P = 0.49), and mean anaerobic power (HIIT85 : +0.42 +/- 0.69 W/kg; HIIT115 : +0.55 +/ 0.65 W/kg; Time effect P = 0.01; Group effect: P = 0.18). Six weeks of submaximal and supramaximal interval training performed to exhaustion seems to equally improve VO2max and anaerobic power in endurance-trained men, despite half the accumulated time spent at the target intensity. PMID- 26887356 TI - NO2-induced performance enhancement of PEDOT:PSS/Si hybrid solar cells with a high efficiency of 13.44. AB - Using poly (3,4-ethylene-dioxythiophene): poly(styrenesulfonate) ( PEDOT: PSS) as an effective hole collecting layer, high-efficiency PEDOT: PSS/n-Si hybrid solar cells are fabricated and a power conversion efficiency (PCE) of 12.13% is obtained. After being treated by HNO3 vapor, the PCE value of PEDOT: PSS/n-Si hybrid solar cells enhances from 12.13% to 13.44%. NO2 gas molecules in HNO3 vapor play a significant doping role in raising the PCE of solar cells. As the doping level raises, NO2 would get more electrons from PEDOT and lead to the increase of hole carriers in the films, which improves the polymer film's conductivity and PCE of solar cells. PMID- 26887355 TI - Carotid inter-adventitial diameter is more strongly related to plaque score than lumen diameter: An automated tool for stroke analysis. AB - PURPOSE: To compare the strength of correlation between automatically measured carotid lumen diameter (LD) and interadventitial diameter (IAD) with plaque score (PS). METHODS: Retrospective study on a database of 404 common carotid artery B mode sonographic images from 202 diabetic patients. LD and IAD were computed automatically using an advanced computerized edge detection method and compared with two distinct manual measurements. PS was computed by adding the maximal thickness in millimeters of plaques in segments taken from the internal carotid artery, bulb, and common carotid artery on both sides. RESULTS: The coefficient of correlation was 0.19 (p < 0.007) between LD and PS, and 0.25 (p < 0.0006) between IAD and PS. After excluding 10 outliers, coefficient of correlation was 0.25 (p < 0.0001) between LD and PS, and 0.38 (p < 0.0001) between IAD and PS. The precision of merit of automated versus the two manual measurements was 96.6% and 97.2% for LD, and 97.7% and 98.1%, for IAD, respectively. CONCLUSIONS: Our automated measurement system gave satisfying results in comparison with manual measurements. Carotid IAD was more strongly correlated to PS than carotid LD in this population sample of Japanese diabetic patients. PMID- 26887357 TI - Hydrate-based heavy metal separation from aqueous solution. AB - A novel hydrate-based method is proposed for separating heavy metal ions from aqueous solution. We report the first batch of experiments and removal characteristics in this paper, the effectiveness and feasibility of which are verified by Raman spectroscopy analysis and cross-experiment. 88.01-90.82% of removal efficiencies for Cr(3+), Cu(2+), Ni(2+), and Zn(2+) were obtained. Further study showed that higher R141b-effluent volume ratio contributed to higher enrichment factor and yield of dissociated water, while lower R141b effluent volume ratio resulted in higher removal efficiency. This study provides insights into low-energy, intensive treatment of wastewater. PMID- 26887358 TI - Mechanism of Inhibition of Human Islet Amyloid Polypeptide-Induced Membrane Damage by a Small Organic Fluorogen. AB - Human islet amyloid polypeptide (hIAPP) is believed to be responsible for the death of insulin-producing beta-cells. However, the mechanism of membrane damage at the molecular level has not been fully elucidated. In this article, we employ coarse- grained dissipative particle dynamics simulations to study the interactions between a lipid bilayer membrane composed of 70% zwitterionic lipids and 30% anionic lipids and hIAPPs with alpha-helical structures. We demonstrated that the key factor controlling pore formation is the combination of peptide charge-induced electroporation and peptide hydrophobicity-induced lipid disordering and membrane thinning. According to these mechanisms, we suggest that a water-miscible tetraphenylethene BSPOTPE is a potent inhibitor to rescue hIAPP induced cytotoxicity. Our simulations predict that BSPOTPE molecules can bind directly to the helical regions of hIAPP and form oligomers with separated hydrophobic cores and hydrophilic shells. The micelle-like hIAPP-BSPOTPE clusters tend to be retained in the water/membrane interface and aggregate therein rather than penetrate into the membrane. Electrostatic attraction between BSPOTPE and hIAPP also reduces the extent of hIAPP binding to the anionic lipid bilayer. These two modes work together and efficiently prevent membrane poration. PMID- 26887360 TI - Clues from oculomotor phenotype to genotype in CACNA1A channelopathies. PMID- 26887359 TI - Longitudinal relaxation time editing for acetylcarnitine detection with 1 H-MRS. AB - PURPOSE: Acetylcarnitine formation is suggested to be crucial in sustaining metabolic flexibility and glucose homeostasis. Recently, we introduced a method to detect acetylcarnitine in vivo with long TE 1 H-MRS. Differences in T1 relaxation time between lipids and acetylcarnitine can be exploited for additional lipid suppression in subjects with high myocellular lipid levels. METHODS: Acquisition of spectra with an inversion recovery sequence was alternated with standard signal acquisition to suppress short T1 metabolite signals. A proof of principle experiment was conducted in a lean subject and the new approach was subsequently tested in four overweight/obese subjects. RESULTS: Using the new T1 editing approach, lipid signals in spectra of skeletal muscle can be (additionally) suppressed by a factor of 10 using a TI of 900 ms. Combination of the long TE protocol with the T1 editing resulted in a well resolved acetylcarnitine peak in the obese subjects. CONCLUSION: The T1 editing approach suppresses short T1 metabolites and offers a new contrast in 1 H-MRS. The approach should be used in combination with a long TE in subjects with high lipid contamination for accurate quantification of the acetylcarnitine concentration. Magn Reson Med 77:505-510, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26887362 TI - [Targeting primary and secondary prevention of stroke]. PMID- 26887361 TI - Transcriptome analysis reveals a diverse family of kinesins essential for spermatogenesis in the fern Marsilea. AB - The male gametophyte of the semi-aquatic fern, Marsilea vestita, produces multiciliated spermatozoids in a rapid developmental sequence that is controlled post-transcriptionally when dry microspores are placed in water. Development can be divided into two phases, mitosis and differentiation. During the mitotic phase, a series of nine successive division cycles produce 7 sterile cells and 32 spermatids in 4.5-5 h. During the next 5-6 h, each spermatid differentiates into a corkscrew-shaped motile spermatozoid with ~140 cilia. In order to study the mechanisms that regulate spermatogenesis, we used RNAseq to generate a reference transcriptome that allowed us to assess abundance of transcripts at different stages of development. Here, we characterize transcripts present in the kinesin motor family. Over 120 kinesin-like sequences were identified in our transcriptome that represent 56 unique kinesin transcripts. Members of the kinesin-2, -4, -5, -7, -8, -9, -12, -13, and -14 families, in addition to several plant specific and 'orphan' kinesins are present. Most (91%) of these kinesin transcripts change in abundance throughout gametophyte development, with 52% of kinesin mRNAs enriched during the mitotic phase and 39% enriched during differentiation. Functional analyses of six kinesins with different patterns of transcript abundance show that the temporal regulation of these transcripts during gametogenesis correlates directly with kinesin protein function. PMID- 26887363 TI - [The prevalence and status of pre-hospital treatments of risk factors among patients with stroke in China]. AB - OBJECTIVE: To analyze the distribution and treatment of risk factors in hospitalized stroke patients before stroke onset. METHOD: This was a multi-center cross-sectional study. Patients with acute stroke were collected from 41 hospitals in 25 provinces in China from January to May in 2011. RESULTS: A total of 20 570 stoke patients (13 062 men, 7 508 women) aged (63.0 +/- 12.9) years were enrolled and analyzed in this study. Among them, 15 329 were first-onset stroke, and 17 052 were ischemic stroke. (1) Of all the subjects, 75.5% were with hypertension, 53.5% with elevated LDL-C, 37.3% with diabetes, and 6.5% with atrial fibrillation. 75.2% of them had two or more above risk factors and 43.0% had three or more risk factors. (2) According to the current definition, 53.3% of the first-onset stroke patients were classified as at high risk and 25.9% were classified as at low risk. Noticeably, 42.1% of the patients below 65 years old were at low risk by the same definition. (3) The awareness rate of hypertension was 70.3% in the first-onset stroke patients. However, only 20.1% of the patients reached the target of blood pressure control in the treatment. Although the awareness rate of hypertension and diabetes among recurrent stroke patients were relatively high, the treatment and control rates of these risk factors were still low. Compared with the other two risk factors, the awareness, treatment and control rates of elevated LDL-C were much lower. CONCLUSIONS: Majority of the stroke patients are complicated with multiple risk factors before stroke onset, suggesting a great needs for improving the primary and secondary prevention of stroke in China. In addition, the definition for risk classification of stroke may need to be modified for subjects under 65 years old. PMID- 26887364 TI - [The clinical analysis of plakophilin-2 gene mutation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia]. AB - OBJECTIVE: The purpose of this study was to screen genetic variations in plakophilin-2 (PKP2) gene in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and investigate the differences in clinical features between mutation and no-mutation groups. METHODS: Thirty unrelated Chinese patients clinically diagnosed with ARVC/D and 50 healthy controls were included. Genomic DNA was isolated from peripheral blood samples. PCR and direct sequencing were used to detect variations in PKP2 gene. RESULTS: Eight PKP2 mutant variants were identified in 10 ARVC/D patients (8 men, 2 women). Among the eight mutation, three (c.2194C>T, c. 1170+ 1G>A and c. 810_813delGGTC) were novel mutation. Clinical features of the PKP2 mutation group were similar to those of the non-mutation group. CONCLUSIONS: The rate of PKP2 mutation is 33.3% (10/30) in ARVC/D patients. The penetrance of PKP2 mutation for ARVC/D tends to be higher in man patients. No significant differences could be detected in phenotype characteristics between patients with and without PKP2 mutation. PMID- 26887365 TI - [Gender difference in the prognostic value of renal dysfunction in patients with ST-segment elevation myocardial infarction]. AB - OBJECTIVE: To evaluate the gender difference in the prognostic value of admission renal dysfunction (RD) for patients with acute ST-segment elevation (STEMI). METHODS: This was a multicenter, prospective cohort study. Four hundred and fifty STEMI patients within 24 h of onset and discharged successfully from 19 hospitals in Beijing were included in the study. All the patients were followed up six years later.According to gender, patients were categorized into two groups. Clinical characteristics, reperfusion therapy conditions and outcomes were analyzed. Multivariate Cox regression analysis was used to evaluate the possible gender difference in the prognostic value of RD. RESULTS: Among all the subjects, 342 were men and 108 were women with age of (61.3+/-12.5) years. Compared to man patients, women were older (P<0.001), and more subjects were with hypertension (67.6% vs 49.7 %, P=0.005), stroke (15.7% vs 8.8%, P=0.039) and RD (17.9% vs 6.7%, P=0.001). After adjustment of age, past medical history, and acute reperfusion therapy. Cox regression analysis showed that RD was associated with the risk of all-cause mortality (HR 3.771, 95%CI 1.382-10.294, P=0.010) and major adverse cardiovascular events (MACE, HR 2.292, 95%CI: 1.091-4.817, P=0.029) in male patients.However, the associations between RD and all-cause mortality (HR 0.889, 95%CI 0.241-3.281, P=0.859), and MACE (HR 1.508, 95%CI 0.616-3.693, P=0.368) were disappeared in women.The interaction test showed that there existed significant interactions between gender and RD in all-cause mortality (HR 2.709, 95%CI 1.150-6.384, P=0.023) and MACE (HR 1.977, 95%CI 1.009-3.876, P=0.023). CONCLUSIONS: There is a considerable gender difference in the prognostic value of RD for the outcomes in patients with STEMI. RD seemed to be an important prognostic maker in male patients. PMID- 26887366 TI - [Minocycline quadruple versus tailored therapy in retreatment of Helicobacter pylori infection]. AB - OBJECTIVE: To compare eradication rates, safety and compliance of minocycline quadruple and tailored therapies in patients retreated for Helicobacter pylori (H.pylori) infection. METHODS: Between January 2014 and June 2014, 135 patients with dyspepsia (18-70 years) and H. pylori infection after at least one previous eradication treatment at a tertiary hospital were randomly assigned to a 10-day treatment with minocycline quadruple therapy versus tailored triple regimen of PPI, amoxicillin and a third antibiotic. In the group of tailored therapy, medications were adjusted based on clarithromycin sensitivity and cytochrome P450 isoenzyme 2C19 genotype. Eradication status was assessed 4-12 weeks after treatment. RESULTS: Although H. pylori eradication rates were higher in the minocycline therapy group than that in the tailored therapy group in intention-to treat [84.1% (95%CI 75.0%-93.2%) vs 75.8%(95%CI 65.1%-86.5%), P=0.245] and per protocol [88.3% (95%CI 80.3%-96.3%) vs 79.7%(95%CI 69.7%-89.7%), P=0.197] analyses, the differences between the two groups were not statistically significant.The incidence of adverse effects and compliance between the two groups were also comparable. CONCLUSIONS: The tailored therapy in this study had a poor eradication efficacy in the retreated patients with H. pylori infection.Minocycline quadruple therapy achieved a relatively satisfactory eradication efficacy and may be an alternative choice for the retreatment of H. pylori infection. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-13003975. PMID- 26887367 TI - [A multicenter retrospective etiological analysis of 601 patients with hemophagocytic lymphohistiocytosis in China]. AB - OBJECTIVE: To investigate the prevalence and etiology of hemophagocytic lymphohistiocytosis (HLH) in different age groups. METHODS: Clinical data of patients with HLH were retrospectively collected from June 2005 to March 2014 in 49 hospitals in China. These patients were divided into child, youth, middle-aged and elderly groups according to the age of onset; meanwhile divided into primary HLH group, infection-associated HLH group, tumor-associated HLH group, rheumatic disease-associated HLH group according to the etiology. Prevalence rates, gender and underlying diseases of each group were retrospectively analyzed. RESULTS: A total of 601 patients were included in the study, age ranging from 1 month to 82 years. The median age of onset was 27 years and 26 years respectively in males(316 cases) and females (285 cases) without statistical significance (P=0.622). There were 171 in child group (28.5%); 262 in youth group(43.6%); 104 in middle-aged group(17.3%); 64 in elderly group(10.6%). The most common causes were infections in child group, malignancies and infections in youth group, malignancies in middle-aged group as well as elderly group. There were 48 patients in primary HLH group(8.0%), 197 in infection-associated HLH group(32.78%), 208 in tumor-associated HLH group(34.61%), 56 in rheumatic disease associated HLH group(9.32%). Patients with primary HLH were significantly younger than those with secondary HLH (P<0.001), however the tumor-associated HLH group was the eldest. Primary HLH, infection-associated HLH and tumor-associated HLH had more male patients but without statistical significance (P=0.196), while rheumatic disease-associated HLH was mostly female patients (P<0.001). CONCLUSIONS: HLH is not a disease peculiar to children, instead, it may occur in all ages. There are a variety of etiology in different age groups, and a possible link between sex and HLH development. In clinical practice, due attention should be paid to the patients with suspected HLH. Positive relevant inspections may aid in the final diagnosis. PMID- 26887369 TI - [A retrospective study of the impact of diabetes mellitus on survival in patients with lung cancer]. AB - OBJECTIVE: To investigate the impact of diabetes mellitus (DM) on survival in patients with lung cancer. METHODS: This is a retrospective study of 1 096 patients died from lung cancer collected from clinical records in Chinese PLA General Hospital. Survival time of lung cancer with and without DM was compared using Log-rank analysis and Cox regression model. RESULTS: One hundred and eighty one patients (16.5%) had DM. The median survival time of the lung cancer patients with DM was 9 months, whereas, the median survival time of the patients without DM was 8 months. Log-rank analysis showed that this difference was significant (P<0.05). Moreover, the 1-, 2-, and 3-year survival rate in lung cancer patients with and without DM were 43% vs 35%, 27% vs 17%, and 16% vs 10%, respectively. After adjusting for age, gender, histology, stage of lung cancer and treatment, Cox regression analysis showed that the hazard ratio for survival in lung cancer patients with DM was 0.74 (95%CI 0.61-0.89, P<0.05) compared with those without DM. In non-small-cell lung cancer(NSCLC)patients, the hazard ratio for survival in lung cancer patients with DM was 0.69 (95%CI 0.56-0.85, P<0.05). However, this association disappeared in small-cell lung cancer (SCLC) patients. In advanced lung cancer patients (stage III-IV), diabetes was also a significant factor for survival (HR=0.74, 95%CI 0.61-0.91, P<0.05). CONCLUSION: Patients with advanced NSCLC with DM have longer survival time compared with those without DM. PMID- 26887368 TI - [The clinical analysis of orthotopic liver transplantation for primary biliary cirrhosis]. AB - OBJECTIVE: To analyze the clinical outcome and complications of orthotopic liver transplantation (OLT) for patients with primary biliary cirrhosis(PBC). METHODS: Clinical data of 25 patients with PBC who underwent OLT were analyzed retrospectively. The postoperative cumulative survival rate of the patients was calculated. The postoperative recurrence of PBC, de novo diseases and other complications were analyzed. RESULTS: A total of 25 patients were recruited including 22 females and 3 males. The average age was 49.1 years (range from 40 to 64 years). The score of model for end-stage liver disease (MELD) was 21.80+/ 5.49, and the Mayo score 8.01+/-1.38. Four patients died after liver transplantation. The 1-year, 2-year and 7-year patient cumulative survival rates were 92.0%, 87.8% and 75.3%, respectively. Eight cases (32.0%) developed recurrent PBC based on histological evidence. The median time to recurrence was 17.5 months. One of the eight patients with recurrent PBC was diagnosed with de novo auto-immune hepatitis (AIH) simultaneously, who eventually died. Acute rejection and de novo hepatitis B virus (HBV) infection developed in thirteen (52.0%) patients and five (20.0%) patients, respectively. Two cases (8.0%) of de novo AIH were diagnosed, one of which was fatal. CONCLUSIONS: OLT is an effective procedure for end-stage PBC. Much attention needs to be paid to the post transplantation complications, including recurrence of primary disease, combined de novo HBV infection, de novo AIH, etc. PMID- 26887370 TI - [A comparative study of IgA nephropathy secondary to ankylosing spondylitis and primary IgA nephropathy]. AB - OBJECTIVE: To study the characteristics of IgA nephropathy (IgAN) secondary to ankylosing spondylitis (AS) compared with primary IgAN. METHODS: Clinical and pathologic data were collected in patients who were diagnosed with IgAN by renal biopsy and admitted to our hospital from Jan 2007 to Sep 2015. Patients with IgAN secondary to AS were recruited by the ratio 1:5 of patients with primary IgAN as control group at the same period. RESULTS: There were 15 patients in AS group, proportionately 75 patients in the control group. Compared with those in control group, patients in AS group had shorter disease course [(10.1+/-8.3) months vs (20.2+/-27.9) months] and lower proportions of renal insufficiency and hypertension[1/15 vs 52.0%(39/75); 1/15 vs 46.7%(35/75)]. In laboratory tests, quantitative 24 hour urinary protein and serum creatinine were significantly lower in group AS than those in the control group [(1.42+/-0.67)g vs (2.88+/ 1.35)g; (79.0+/-18.2)mmol/L vs (145.3+/-77.6) mmol/L]. The Lee grading of IgAN in two groups was comparable. The treatment in both groups was similar including steroids, immunosuppression agents, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers . After follow-up from 1 to 6 years, 3/11 patients in AS group and 22.8%(13/57)(13/75) in control group developed deterioration of renal function. CONCLUSION: Patients with IgAN secondary to AS have shorter disease course and milder condition compared with patients with primary IgAN. Clinical outcome of renal function in both groups is similar according to comparable treatment. PMID- 26887371 TI - [Pulmonary hypertension in patients with chronic obstructive pulmonary disease: clinical characteristics and risk factors]. AB - OBJECTIVE: To investigate the clinical characteristics of pulmonary hypertension(PH) in patients with chronic obstructive pulmonary disease(COPD) and study the related risk factors. METHODS: Patients with stable COPD enrolled in this study, undergoing examinations including full pulmonary function tests (PFT), 6-minute walk distance (6MWD), Exercise Oxyhemoglobin, Saint. George's respiratory questionnaire (SGRQ) and transthoracic echocardiography. Pulmonary artery systolic pressure(sPAP) >=36 mmHg (1 mmHg=0.133 kPa) was defined as PH. RESULTS: A total of 251 patients were finally evaluable in this study. The frequency of PH was 55.4% (139/251) in patients with stable COPD. Significant differences were seen between patients with PH and without PH respectively in the following factors (mean P<0.05): proportion of age >= 60 years (69.8% vs 57.1%), forced expiratory volume in one second (FEV(1)) (% predicted) [(47.5+/-8.2)% vs (61.2+/-10.2)% and (49.8+/-7.9)% vs (66.4+/-11.3)%], sPAP [(41.9+/-9.1) mmHg vs (28.2+/-3.2) mmHg], exercise oxyhemoglobin desaturation [(-5.5+/-3.2)% vs (-2.2+/ 1.2)%], 6MWD [(316.0+/-55.2)m vs (390.0+/-75.2)m]. The following variables were negatively correlated with sPAP : 6MWD (r=-0.330, P=0.003), FEV(1)(% predicted) (r=-0.210, P=0.024 and r=-0.130, P=0.012, respectively). The following variables were positively correlated with sPAP: age (r= 0.560, P= 0.031), exercise oxyhemoglobin desaturation> 3% (r= 0.540, P= 0.001). Logistic regression test has showed that age >= 60 years, exercise oxygen desaturation>3%, FEV(1) (% predicted) <50%, 6MWD <350 m were risk factors for PH in COPD. CONCLUSION: The incidence of PH in COPD increases with age, yet the performance of lung function and the activity of endurance decrease in elder patients. Sixty years or older, exercise oxygen desaturation> 3%, FEV(1) (% predicted) <50%, 6MWD <350 m are risk factors of PH in COPD. Echocardiography or right heart catheterization when needed should be considered to confirm the diagnosis. PMID- 26887372 TI - Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF-kappaB-Regulated Anti-Apoptosis and p53/PCNA- and ATM/ATR Chk1/2-Controlled DNA-Damage Response Pathways. AB - Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6-10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up- and down-regulation of pro-apoptotic and anti-apoptotic genes, respectively. Moreover, up- and down regulation of pro-apoptotic (Caspases 3, 7, 8) and anti-apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF-kappaB-p65, which is complemented by the predominant localization of NF kappaB-p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF-kappaB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down-regulated in cells exposed to SMG, among which down regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. In addition, we demonstrate a significant inhibition of molecules involved in the DNA-damage response, such as p53, PCNA, ATM/ATR, and Chk1/2. Taken together, our work reveals that SMG promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF-kappaB-regulated apoptosis and the p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways. Thus, our investigation provides novel information, which may help us to determine the cause of negative alterations in human physiology occurring at spaceflight environment. J. Cell. Biochem. 117: 2138-2148, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26887373 TI - Interobserver agreement of Neer and AO classifications for proximal humeral fractures. AB - BACKGROUND: The classification of proximal humeral fractures remains challenging. The two main classification systems used, the Neer and the AO classification, have both been shown to have less than ideal interobserver agreement. Agreement in classification is required, however, to guide fracture management. METHOD: Data from the Victorian Orthopaedic Trauma Outcomes Registry were collected and the X-rays of 104 proximal humeral fractures were reviewed by three orthopaedic consultants. They classified the fractures according to the Neer and AO classifications, as well as their simplified versions. Interobserver agreement was then assessed using kappa statistics. RESULTS: Interobserver agreement was better overall in the Neer classification, which was moderate (kappa = 0.40 0.58), than the AO classification, which was fair to moderate (kappa = 0.31 0.54). When simplified, the Neer and AO classification interobserver agreement remained similar. CONCLUSION: The classification of proximal humeral fractures with both the Neer and the AO systems remains difficult with minimal improvements seen when reducing the number of categories in each classification system. From these results, the Neer classification system would appear slightly more useful in clinical practice to guide treatment. PMID- 26887374 TI - Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors. AB - Ramucirumab (IMC-1121B, LY3009806) is a fully human G1 monoclonal antibody that specifically targets vascular endotelial growth factor receptor 2 (VEGFR-2) with a substantially greater binding affinity than that of its natural ligands. Early clinical trials in patients with advanced solid tumors demonstrated that biologically relevant blood target concentrations are achievable with tolerable doses, and also showed some preliminary evidence of clinical activity. Several pivotal phase III trials have now been concluded and have led regulatory agencies to grant marketing authorization to ramucirumab for use as second line therapy in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (as single agent or in combination with paclitaxel), in patients with advanced colorectal carcinoma (CRC) (in combination with infusional fluorouracil and irinotecan (FOLFIRI regimen)) and in patients with advanced non-small cell lung cancer (NSCLC) (in combination with docetaxel). In contrast, ramucirumab failed to significantly improve survival versus placebo as second line therapy in patients with advanced hepatocellular carcinoma (HCC). The aim of this review is to summarize the clinical development and emerging role of ramucirumab in gastrointestinal (GI) tumors, including relevant aspects of its mechanism of action, pharmacology, safety profile, and antitumor activity in gastric, HCC, and CRC carcinomas. PMID- 26887375 TI - PlanTE-MIR DB: a database for transposable element-related microRNAs in plant genomes. AB - Transposable elements (TEs) comprise a major fraction of many plant genomes and are known to drive their organization and evolution. Several studies show that these repetitive elements have a prominent role in shaping noncoding regions of the genome such as microRNA (miRNA) loci, which are components of post transcriptional regulation mechanisms. Although some studies have reported initial formation of miRNA loci from TE sequences, especially in model plants, the approaches that were used did not employ systems that would allow results to be delivered by a user-friendly database. In this study, we identified 152 precursor miRNAs overlapping TEs in 10 plant species. PlanTE-MIR DB was designed to assemble this data and deliver it to the scientific community interested in miRNA origin, evolution, and regulation pathways. Users can browse the database through a web interface and search for entries using various parameters. This resource is cross-referenced with repetitive element (Repbase Update) and miRNA (miRBase) repositories, where sequences can be checked for further analysis. All data in PlanTE-MIR DB are publicly available for download in several file formats to facilitate their understanding and use. The database is hosted at http://bioinfo-tool.cp.utfpr.edu.br/plantemirdb/ . PMID- 26887376 TI - Cyclic changes in area- and perimeter-derived effective dimensions of the aortic annulus measured with multislice computed tomography and comparison with metric intraoperative sizing. AB - AIMS: Multislice computed tomography (MSCT) is recommended for annular sizing prior to transcatheter aortic valve implantation (TAVI), but it remains unclear whether systolic or diastolic reconstructions should be used and whether the effective annular diameter should be derived by area or perimeter. In this study these different approaches were compared with intraoperative sizing. METHODS: In 52 patients who were evaluated but deemed unsuitable for TAVI, the annulus was measured during conventional surgery using metric sizers (AnnOp) and compared with MSCT measurements (cross-sectional diameter derived by area [AnnAsys, AnnAdia; AnnAmean = (AnnAsys + AnnAdia)/2] and perimeter (AnnPsys, AnnPdia) in systole and diastole). Furthermore, TAVI was simulated based on AnnOp and the impact of the various MSCT approaches on sizing strategy was determined. RESULTS: The best agreement with AnnOp [mean difference (limits of agreement)] was shown for AnnAmean [0.03 mm (-1.9 to 1.96)], whereas the strongest deviation was noted for AnnPsys [-1.08 mm (-3.01 to 0.86)]. Mean differences between systole and diastole were significant but small: 0.82 mm (3.5 %) for area- and 0.81 mm (3.3 %) for perimeter-derived measurements. Simulation of TAVI revealed the least change of strategy for AnnAmean (76.9 %) as compared with AnnPsys (53.8 %); between AnnAsys and AnnAdia sizing would have been deviant in 17.3 % due to relatively large intraindividual cyclic differences. CONCLUSIONS: AnnAmean demonstrated the best agreement with AnnOp, whereas perimeter-derived measurements were somewhat overestimated. Despite a negligible average difference between systolic and diastolic annular values, in a subset of patients the intraindividual cyclic variability was relatively large and potentially of clinical impact. PMID- 26887377 TI - Use of targeted therapy in cancer patients in the end-of-life period: results from an Australian centre. AB - PURPOSE: Data on the use of targeted therapies at the end of life are scarce. This study reviews the pattern of use of targeted and potentially futile, toxic, or costly therapies at an Australian cancer centre. METHODS: This retrospective single-centre review of data from patients who died within 3 months of having targeted therapy examined demographic characteristics, types of cancers, types of therapy, age, and lines of prior therapy. RESULTS: Over 24 months, two groups were analysed. Firstly, 889 patients died with 107 patients who were prescribed targeted therapy. Secondly, 457 patients were treated with targeted therapies with 52 patients, (11 %) dying within 3 months. To focus on the 52 patients: median age was 69 years, 65 % were men and 35 % were women, 50 % had haematologic cancers and 50 % had solid tumours. Ten therapeutic agents were represented: a higher total number of deaths among those prescribed erlotinib, bevacizumab, and rituximab. There were no deaths within 3 months of treatment with trastuzumab, ipilimumab, or vemurafenib. The targeted therapy was the first-line treatment in 54 %, second in 15 %, and third and beyond in 15 %. The patient's sex and type of cancer had no statistically significant influence on death within 3 months of targeted treatment. CONCLUSIONS: The use of targeted therapy at the end of life in this single-centre descriptive study was lower than documented in other studies. There is a need to prospectively document the factors leading to this prescribing behaviour to guide future protocols. PMID- 26887378 TI - Multicenter phase II study of an oral care program for patients with head and neck cancer receiving chemoradiotherapy. AB - PURPOSE: This multicenter phase II trial assessed the clinical benefit of a multidisciplinary oral care program in reducing the incidence of severe chemoradiotherapy-induced oral mucositis (OM). METHODS: Patients with head and neck cancer (HNC) who were scheduled to receive definitive or postoperative chemoradiotherapy were enrolled. The oral care program included routine oral screening by dentists and a leaflet containing instructions regarding oral care, nutrition, and lifestyle. Oral hygiene and oral care were evaluated continuously during and after the course of chemoradiotherapy. The primary endpoint was the incidence of grade >=3 OM assessed by certified medical staff according to the Common Terminology Criteria of Adverse Events version 3.0. RESULTS: From April 2012 to December 2013, 120 patients with HNC were enrolled. Sixty-four patients (53.3 %) developed grade >=3 OM (i.e., functional/symptomatic). The incidence of grade <=1 OM at 2 and 4 weeks after radiotherapy completion was 34.2 and 67.6 %, respectively. Clinical examination revealed that 51 patients (42.5 %) developed grade >=3 OM during chemoradiotherapy. The incidence of grade <=1 OM at 2 and 4 weeks after radiotherapy completion was 54.7 and 89.2 %, respectively. The incidences of grade 3 infection and pneumonitis throughout chemoradiotherapy were <5 %. Only 6.7 % of patients had unplanned breaks in radiotherapy, and 99.2 % completed treatment. CONCLUSIONS: A systematic oral care program alone is insufficient to decrease the incidence of severe OM in patients with HNC being treated with chemoradiotherapy. However, systematic oral care programs may indirectly improve treatment compliance by decreasing infection risk. TRIAL REGISTRATION NUMBER: UMIN000006660. PMID- 26887379 TI - Exome-Wide Association Study Identified New Risk Loci for Hirschsprung's Disease. AB - Hirschsprung disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. In this study, we aimed to investigate the genetic loci involved in the pathogenesis of HSCR. The exome-wide scan was performed to screen the genetic variants with minor allele frequency (MAF) < 0.05 in exonic regions. Candidate mutation type and the wild type were overexpressed to investigate the affection on cell proliferation and migration. We found that ten variants were associated with HSCR at P < 10-4 in the single variant analysis while ten genes were also associated with HSCR at P < 10-4 in the optimized sequence kernel association test (SKAT-O) test analysis. Among these SNPs, the missense variants catechol-O-methyltransferase (COMT) (rs6267) and armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) (rs80068543) indicated an ectopic expression in colon tissues of HSCR patients. The Ala72Ser variant in COMT induced proliferation suppression through NOTCH signal pathway, while the ARVCF affected cell migration via the downregulating of RHOA and ROC. In conclusion, this exome array study identified the COMT and ARVCF missense coding variants as candidate loci for HSCR. The finding implies the abnormal variant of COMT and ARVCF may account for the pathogenesis of HSCR. PMID- 26887380 TI - The Brain NO Levels and NOS Activities Ascended in the Early and Middle Stages and Descended in the Terminal Stage in Scrapie-Infected Animal Models. AB - The infections of prion agents may cause progressive and fatal neurodegenerative diseases in humans and a serial of animal species. Previous studies have proposed that the levels of nitric oxide (NO) and nitric oxide synthase (NOS) in the brains of some neurodegeneration diseases changed, while S-nitrosylation (SNO) of many brain proteins altered in prion diseases. To elucidate the potential changes of brain NO levels during prion infection, the NO levels and NOS activities in the brain tissues of three scrapie experimental rodents were measured, including scrapie agent 263 K-infected hamsters and 139A- and ME7-infected mice. Both NO levels and NOS activities, including total NOS (TNOS) and inducible NOS (iNOS), were increased at the terminal stages of scrapie-infected animals. Assays of the brain samples collected at different time points during scrapie infection showed that the NO levels and NOS activities started to increase at early stage, reached to the peak in the middle stage, and dropped down at late stage. Western blots for brain iNOS revealed increased firstly and decreased late, especially in the brains of 139A- and ME7-infected mice. In line with those alterations, the levels of the SNO forms of several selected brain proteins such as aquaporin-1 (AQP1), calcium/calmodulin-dependent protein kinase II (CaMKII), neurogranin, and opalin, underwent similar changing trends, while their total protein levels did not change obviously during scrapie infection. Our data here for the first time illustrate the changing profile of brain NO and NOS during prion infection. Time dependent alterations of brain NO level and the associated protein S nitrosylation process may contribute greatly to the neuropathological damage in prion diseases. PMID- 26887381 TI - Adoptive Autophagy Activation: a Much-Needed Remedy Against Chemical Induced Neurotoxicity/Developmental Neurotoxicity. AB - The profound significance of autophagy as a cell survival mechanism under conditions of metabolic stress is a well-proven fact. Nearly a decade-long research in this area has led scientists to unearth various roles played by autophagy other than just being an auto cell death mechanism. It is implicated as a vital cell survival pathway for clearance of all the aberrant cellular materials in case of cellular injury, metastasis, disease states, cellular stress, neurodegeneration and so on. In this review, we emphasise the critical role of autophagy in the environmental stressors-induced neurotoxicity and its therapeutic implications for the same. We also attempt to shed some light on the possible protective role of autophagy in developmental neurotoxicity (DNT) which is a rapidly growing health issue of the human population at large and hence a point of rising concern amongst researchers. The intimate association between DNT and neurodegenerative disorders strongly indicates towards adopting autophagy activation as a much-needed remedy for DNT. PMID- 26887382 TI - Prevention of Hippocampal Neuronal Damage and Cognitive Function Deficits in Vascular Dementia by Dextromethorphan. AB - Dextromethorphan (DM) is a non-competitive antagonist of NMDA receptors and a widely used component of cough medicine. Recently, its indication has been extended experimentally to a wide range of disorders including inflammation mediated central nervous system disorders such as Parkinson disease (PD) and multiple sclerosis (MS). In this study, we investigate whether DM treatment has protective effects on the hippocampal neuron damage induced by bilateral occlusion of the common carotid arteries (two-vessel occlusion [2VO]), an animal model of vascular dementia (VaD). Sprague-Dawley (SD) (10 weeks of age) rats were subjected to the 2VO, and DM was injected intraperitoneally once per day for 37 days. Neuron death, glial activation, and cognitive function were assessed at 37 days after 2VO (0.2 mg/kg, i.p., "DM-0.2" and 2 mg/kg, i.p., "DM-2"). DM-2 treatment provided protection against neuronal death and glial activation in the hippocampal CA1 subfield and reduced cognitive impairment induced by 2VO in rats. The study also demonstrates that activation of the Nrf2-HO-1 pathway and upregulation of superoxide dismutase (SOD) play important roles in these effects. These results suggest that DM is effective in treating VaD and protecting against oxidative stress, which is strongly implicated in the pathogenesis of VaD. Therefore, the present study suggests that DM treatment may represent a new and promising protective strategy for treating VaD. PMID- 26887384 TI - The Critical Role of SRPK1 in EMT of Human Glioblastoma in the Spinal Cord. AB - Up to now, the serine-arginine protein kinase 1 (SRPK1) has been suggested as an important signal mediator, which is implicated in the development of cancers. Unfortunately, some molecular pathways in SRPK1-mediated epithelial-mesenchymal transition (EMT) in human spinal glioblastoma have been not elucidated. In this work, we detected the expression of SRPK1 in human spinal glioblastoma tissues and GBM cell lines and analyzed the relevant molecular proteins using in vitro experiments, including RT-PCR, gene silencing, and Western blot. In this study, RT-PCR and Western blot revealed that the expression of SRPK1 mRNA and protein became higher in all six spinal glioblastoma specimens; however, its expression was low in matched normal specimens. We also demonstrated SRPK1 expression facilitated the proliferation of U87 and U251 cells and inhibited the apoptosis in U87 and U251 cells. Also, SRPK1 promoted the expression of EMT-regulating markers, involving N-cadherin, Snail, and MMP9 and decreased the expression of mesenchymal marker E-cadherin. Moreover, knockdown of SRPK1 significantly inhibited the expression levels of p-Akt rather than t-Akt. In conclusion, knockdown of SRPK1 inhibited glioblastoma cell proliferation, invasion, and EMT process via suppressing p-Akt signaling pathway. This study also lays a new foundation for the clinically biological treatment. PMID- 26887383 TI - Pharmacological Inhibition of PERK Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats Through the Activation of Akt. AB - Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Endoplasmic reticulum (ER) stress was reported to have a vital role in the pathophysiology of neuronal apoptosis in the brain. The present study was designed to investigate the potential effects of ER stress and its downstream signals in early brain injury after SAH. One hundred thirty four rats were subjected to an endovascular perforation model of SAH. The RNA activated protein kinase-like ER kinase (PERK) inhibitor GSK2606414 and the Akt inhibitor MK2206 were injected intracerebroventricularly. SAH grade, neurologic scores, and brain water content were measured 72 h after subarachnoid hemorrhage. Expression of PERK and its downstream signals, Akt, Bcl-2, Bax, and cleaved caspase-3, were examined using Western blot analysis. Specific cell types that expressed PERK were detected with double immunofluorescence staining. Neuronal cell death was demonstrated with terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labeling (TUNEL). Our results showed that the expression of p-PERK and its downstream targets, p-eIF2alpha and ATF4, increased after SAH and peaked at 72 h after SAH. PERK was expressed mostly in neurons. The inhibition of PERK with GSK2606414 reduced p-PERK, p-eIF2alpha, and ATF4 expression. Furthermore, GSK2606414 treatment increased p-Akt levels and the Bcl 2/Bax ratio as well as decreased cleaved caspase-3 expression and neuronal death, thereby improving neurological deficits at 72 h after SAH. The selective Akt inhibitor MK2206 abolished the beneficial effects of GSK2606414. PERK, the major transducer of ER stress, is involved in neuronal apoptosis after SAH. The inhibition of PERK reduces early brain injury via Akt-related anti-apoptosis pathways. PERK may serve as a promising target for future therapeutic intervention. PMID- 26887386 TI - Seven day services will need 4000 extra doctors, says leaked report. PMID- 26887387 TI - Ian Forgacs: Loves skinny dipping. PMID- 26887385 TI - Interferon-beta Inhibits Neurotrophin 3 Signalling and Pro-Survival Activity by Upregulating the Expression of Truncated TrkC-T1 Receptor. AB - Although clinically useful for the treatment of various diseases, type I interferons (IFNs) have been implicated as causative factors of a number of neuroinflammatory disorders characterized by neuronal damage and altered CNS functions. As neurotrophin 3 (NT3) plays a critical role in neuroprotection, we examined the effects of IFN-beta on the signalling and functional activity of the NT3/TrkC system. We found that prolonged exposure of differentiated human SH-SY5Y neuroblastoma cells to IFN-beta impaired the ability of NT3 to induce transphosphorylation of the full-length TrkC receptor (TrkC-FL) and the phosphorylation of downstream signalling molecules, including PLCgamma1, Akt, GSK 3beta and ERK1/2. NT3 was effective in protecting the cells against apoptosis triggered by serum withdrawal or thapsigargin but not IFN-beta. Prolonged exposure to the cytokine had little effects on TrkC-FL levels but markedly enhanced the messenger RNA (mRNA) and protein levels of the truncated isoform TrkC-T1, a dominant-negative receptor that inhibits TrkC-FL activity. Cell depletion of TrkC-T1 by small interfering RNA (siRNA) treatment enhanced NT3 signalling through TrkC-FL and allowed the neurotrophin to counteract IFN-beta induced apoptosis. Furthermore, the upregulation of TrkC-T1 by IFN-beta was associated with the inhibition of NT3-induced recruitment of the scaffold protein tamalin to TrkC-T1 and tamalin tyrosine phosphorylation. These data indicate that IFN-beta exerts a negative control on NT3 pro-survival signalling through a novel mechanism involving the upregulation of TrkC-T1. PMID- 26887388 TI - Regulation of liver development: implications for liver biology across the lifespan. AB - The liver serves a spectrum of essential metabolic and synthetic functions that are required for the transition from fetal to postnatal life. Processes essential to the attainment of adequate liver mass and function during fetal life include cell lineage specification early in development, enzymic and other functional modes of differentiation throughout gestation, and ongoing cell proliferation to achieve adequate liver mass. Available data in laboratory rodents indicate that the signaling networks governing these processes in the fetus differ from those that can sustain liver function and mass in the adult. More specifically, fetal hepatocytes may develop independent of key mitogenic signaling pathways, including those involving the Erk mitogen-activated protein kinases MAPK1/3 and the mechanistic target of rapamycin (mTOR). In addition, the fetal liver is subject to environmental influences that, through epigenetic mechanisms, can have sustained effects on function and, by extension, contribute to the developmental origin of adult metabolic disease. Finally, the mitogen-independent phenotype of rat fetal hepatocytes in late gestation makes these cells suitable for cell-based therapy of liver injury. In the aggregate, studies on the mechanisms governing fetal liver development have implications not only for the perinatal metabolic transition but also for the prevention and treatment of liver disorders throughout the lifespan. PMID- 26887392 TI - [Essence and clinical application of classical directional force system]. PMID- 26887391 TI - Evolutionary history of the chitin synthases of eukaryotes. AB - Chitin synthases are widespread among eukaryotes and known to have a complex evolutionary history in some of the groups. We have reconstructed the chitin synthase phylogeny using the most taxonomically comprehensive dataset currently available and have shown the presence of independently formed paralogous groups in oomycetes, ciliates, fungi, and all diatoms except raphid pennates. There were also two cases of horizontal gene transfer (HGT): transfer from fungus to early diatoms gave rise to diatom paralogous group, while transfer from raphid pennate diatom to Acantamoeba ancestor is, to our knowledge, restricted to a single gene in amoeba. Early evolution of chitin synthases is heavily obscured by paralogy, and further sequencing effort is necessary. PMID- 26887390 TI - Hexosamine biosynthesis in keratinocytes: roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis. AB - UDP-N-acetylglucosamine (UDP-GlcNAc) is a glucose metabolite with pivotal functions as a key substrate for the synthesis of glycoconjugates like hyaluronan, and as a metabolic sensor that controls cell functions through O GlcNAc modification of intracellular proteins. However, little is known about the regulation of hexosamine biosynthesis that controls UDP-GlcNAc content. Four enzymes can catalyze the crucial starting point of the pathway, conversion of fructose-6-phosphate (Fru6P) to glucosamine-6-phosphate (GlcN6P): glutamine fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2). Using siRNA silencing, we studied the contributions of these enzymes to UDP-GlcNAc content and hyaluronan synthesis in human keratinocytes. Depletion of GFAT1 reduced the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both GNPDA1 and GDPDA2 exerted opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyzed the reaction from GlcN6P back to Fru6P. However, when hexosamine biosynthesis was blocked by GFAT1 siRNA, the effect by GNPDAs was reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDP-GlcNAc content. Silencing of these enzymes also changed the gene expression of related enzymes: GNPDA1 siRNA induced GFAT2 which was hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increased GFAT1, and GFAT1 siRNA increased the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulated GNPDA1 and GDPDA2, and inhibited cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer. PMID- 26887389 TI - Mechanisms of uterine estrogen signaling during early pregnancy in mice: an update. AB - Adherence of an embryo to the uterus represents the most critical step of the reproductive process. Implantation is a synchronized event between the blastocyst and the uterine luminal epithelium, leading to structural and functional changes for further embryonic growth and development. The milieu comprising the complex process of implantation is mediated by estrogen through diverse but interdependent signaling pathways. Mouse models have demonstrated the relevance of the expression of estrogen-modulated paracrine factors to uterine receptivity and implantation window. More importantly, some factors seem to serve as molecular links between different estrogen pathways, promoting cell growth, acting as molecular chaperones, or amplifying estrogenic effects. Abnormal expression of these factors can lead to implantation failure and infertility. This review provides an overview of several well-characterized signaling pathways that elucidates the molecular cross talk involved in the uterus during early pregnancy. PMID- 26887393 TI - [Effect of the presurgical nasoalveolar molding using computer-aided design technique]. AB - OBJECTIVE: To develop a new method of presurgical nasoalveolar molding based on computer-aided design technique. METHODS: Twenty patients(16 boys, 4 girls) with complete unilateral cleft lip and palate(UCLP) who received presurgical nasoalveolar molding were recruited as the treatment group. Twenty patients(15 boys, 5 girls) with complete UCLP who did not receive presurgical orthopedic treatment were selected as the control group. All parameters of the digital maxillary model were measured using the Rapidform XOR3 software. The statistical analysis was performed with SPSS 15.0. RESULTS: A'-X and B-Il were reduced significantly after presurgical nasoalveolar molding. However, the mean alveolar height [F- hight (3.7 +/- 1.1) mm, F'-height (4.6 +/- 0.9) mm] decreased significantly after treatment(P <0.05). There were significant differences between the treatment group and the control group(P<0.05). CONCLUSIONS: Maxillary alveolar morphology could be improved in UCLP infants treated with computer-aided presurgical nasoalveolar molding. The width of the cleft could be reduced and the maxillary midline corrected effectively. However, the alveolar height decreased significantly after the treatment. PMID- 26887394 TI - [Mineral trioxide aggragate pulpotomy for the treatment of immature permanent teeth with irreversible pulpitis: a preliminary clinical study]. AB - OBJECTIVE: To evaluate the preliminary clinical effect of mineral trioxide aggragate (MTA) pulpotomy on immature permanent teeth with irreversible pulpitis. METHODS: Twenty-six immature permanent teeth with irreversible pulpitis were recuited from Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology. These teeth were treated with partial or full pulpotomy according to the condition of pulp bleeding. MTA was used as pulp capping material. Patients were recalled periodically after the treatment. Clinical and radiographic effects were evaluated. RESULTS: At one year follow-up, 20 teeth were evaluated as healed or healing, 2 teeth were evaluated as failure and 4 teeth were dropped out. The success rate was considered 91% (20/22). A dentinal bridge was radiographcally observed underneath the pulpotomy site in 13 teeth(65%, 13/20). CONCLUSIONS: MTA pulpotomy is an effective method for the treatment of immature permanent teeth with irreversible pulpitis. But further research with longer follow up period is required. PMID- 26887395 TI - [An experimental study on segmental defects reconstruction of canine mandible with allogenic bone marrow mesenchymal stem cells combined with lyophilized bone]. AB - OBJECTIVE: To investigate the effect of segmental defects reconstruction of canine mandible with allogenenic bone marrow mesenchymal stem cells (BMSC) combined with lyophilized bone. METHODS: A 30 mm segmental defect was created on the left mandibles of beagles. Beagles were randomly divided into three groups. Allogeneic bone marrow mesenchymal stem cells with lyophilized bone were used for segmental defects reconstruction in group A. Autologous bone marrow mesenchymal stem cells with freeze- dried bone were used for segmental defects reconstruction in group B. The defects of group C were repaired with lyophilized bone only. Every three beagles were sacrificed 4, 12, 24, and 48 weeks after surgery respectively. The reconstruction effect was evaluated by CT and histopathological examination. RESULTS: CT examination showed that new bones formed in group A and group B 12 weeks after surgery, but not in group C. The form of the reconstructed mandibles in the three groups recovered in 48 weeks. The small pores on the bone graft were filled with new bones in group A and group B. In group C, the pores were still evident. Histopathological examination showed that bone trabecula between allogeneic bone and autogenous bone was completely joined in group A and group B. A large number of fibrous tissue appeared around the implanted bone and new bones were formed. In group C, the lyophilized bone resorption was still not obvious, the new bone formation was significantly slower than the other two groups. There was no difference between group A and group B. CONCLUSIONS: Both allogeneic bone marrow mesenchymal stem cells and autologous mesenchymal stem cells could accelerate the bone formation. PMID- 26887396 TI - [Bioactive glass 45S5-silk fibroin membrane supports proliferation and differentiation of human dental pulp stem cells]. AB - OBJECTIVE: To investigate the effect of bioactivity glass 45S5- silk fibroin(BG45S5- SF) membrane on growth, proliferation and differentiation of human dental pulp stem cells(hDPSC), and to provide new ideas and method for the regeneration of pulp-dentine complex. METHODS: hDPSC seed on pure silk fibroin membrane (protein membrane group) and BG45S5-SF membrane with different concentrations(1 000, 5 000 mg/L, composite membrane group A and B, respectively) were prepared, and the materials were incubated in cell culture fluid for 24 h. No material membrane orifice plate was used as blank control group. Contact angle meter was used to measure surface contact angle of protein membrane and composite membrane group(each group had three repeated holes). Cell proliferation was assessed by cell counting kit- 8 on the 4, 7, 14, and 21 days. The state of adhesion and growth of hDPSC on the materials surface was evaluated by scanning electron microscopy and cytoskeleton staining; and alkaline phosphatase (ALP) activity was measured to evaluate the cell differentiation potential. The expression of odontoblastic differentiation-related genes was measured by real time PCR. RESULTS: Surface contact angle of the protein membrane group and composite membrane group A and group B were 89.51 degrees +/- 0.12 degrees , 70.32 degrees +/- 0.07 degrees and 71.31 degrees +/- 0.09 degrees respectively. hDPSC adhered well on each materials surface on the 7, 14, 21 days, ALP activity and differentiation genes of composite membrane group A and B rised more significantly than the blank control group and protein membrane group did (P<0.05). Dentin matrix protein1(DMP- 1), dentin sialoprotein(DSP), ALP, osteocalcin(OC) mRNA expression reached peak on the 14 days in group A, and in group B on the 21 days. Bone sialoprotein(BSP) mRNA expression in both group A and B reached peak on the 21 days. CONCLUSIONS: BG45S5- SF membrane is able to support the proliferation and showed the potential of odontoblastic differentiation for hDPSC. This finding suggests that BG45S5-SF membrane was a kind of tissue engineering film material with the regeneration potential for pulp dentine complex. PMID- 26887397 TI - [Effect of tooth extraction and antibiotics on carotid artery wall and serum interleukin 6 in chronic periodontitis rats with or without atherosclerosis]. AB - OBJECTIVE: To investigate the effect of tooth extraction with antibiotics on atherosclerosis, and to examine the expression of serum interleukin 6(IL-6) and the pathological changes of the carotid artery in chronic periodontitis(CP) rats with or without atherosclerosis(As). METHODS: A total of 44 SD rats were randomly divided into four groups, group A(normal control), group B(As), group C(CP), group D(CP+As). After model establishment, group C and group D were randomly divided into group C1/D1 (tooth extraction) and group C2/D2(tooth extraction with antibiotics) according to random number table and received the corresponding oral intervention treatment respectively. Serum IL-6 levels were determined by enzyme linked immunosorbent assay(ELISA) respectively one week before the intervention, one week after the first intervention, one, three, five weeks after the second intervention. The pathological changes of the carotid artery were accessed under light microscope. RESULTS: At all sampling time points, the levels of serum IL-6 in group B, C, D were higher than that of group A, with group D1 being increased most obviously, significantly higher than that of group A(P< 0.001). One week after the second intervention, the content of IL-6 in group C and group D peaked[C1(127.0 +/- 29.9) ng/L, C2: (120.6 +/- 23.1) ng/L, D1: (175.1 +/- 50.8) ng/L, D2: (160.5 +/- 37.7) ng/L], and was significantly higher than that of group B[B: (43.4 +/- 7.5) ng/L,P<0.001]. Then they all had varying degrees of decline, 5 weeks after the second intervention, group C1 and D1 were still higher than that of group B, but group C2 and D2 were lower than that of group B. At all sampling time points, the levels of serum IL- 6 in group C2/D2 were lower than those in group C1/D1, 5 weeks after the second intervention the difference was most obvious and statistically significant(P<0.001). Pathology showed that the carotid artery wall in group A was normal. The carotid artery wall was thickened in group B, inflammatory cells and foam cells could be seen, and elastic fibers disordered. The carotid artery wall in group C1 was uneven, foam cells and a small amount of inflammatory cells were visible, and elastic fiber disordered. Obvious thickening was not seen in the carotid artery wall of group C2, a small amount of foam cells and inflammatory cells were found, and elastic fiber mildly disordered. The carotid artery wall in group D1 was obviously uneven, calcium salt deposits were visible in the artery wall, a large amount of inflammatory cells and foam cells could be found, and elastic fiber disordered. Obvious thickening was not seen in the carotid artery wall of group D2, a small amount of inflammatory cells and a large amount of foam cells could be seen, and elastic fiber disordered. CONCLUSIONS: Periodontitis and hyperlipidemia could increase the level of serum IL- 6 and the risk of the As. In chronic periodontitis rats with or without atherosclerosis, when periodontal inflammation was not controlled, tooth extraction may increase the risk of the As. At the time of tooth extraction, giving the anti-inflammatory treatment can reduce the risk to a certain extent. PMID- 26887398 TI - [Effect of resin infiltration on microhardness of artificial caries lesions]. AB - OBJECTIVE: To compare the changes of enamel surface and cross-sectional microhardness of artificial caries immediately and after the twice demineralization through coating resin infiltration, fluoride varnish and fissure sealant. METHODS: A total of forty bovine lower incisors enamel samples with artificial caries lesions by the demineralization liquid were used in the experiment. The specimens were then randomly divided into four groups as group A(resin infiltration), B(fluoride varnish), C (fissure sealant), D(control), 10 specimens in each group. The samples were sectioned vertically into two halves through the centre. One half of each sample the surface and cross-sectional microhardness was measured. The other half was put into demineralization liquid for 14 days, then the surface and cross-sectional microhardness was measured again. The cross section morphology of the samples was observed by scanning electron microscope. RESULTS: The surface of enamel had the highest microhardness value, and with the increase of cross- sectional depth, the microhardness value declined gradually. Variance analysis showed that the difference was statistically significant in the cross-section of different depth among the four groups(P<0.05). The microhardness values of the surface and the cross- section at 40 um of each group in immediate measure showed the values were significantly higher in group A, B and C than in group D. There was no significant difference in the microhardness value of cross-section at 80 um between group A[(324 +/- 17) kg/mm(2)] and group C[(316 +/- 20) kg/mm(2)], but they were significantly higher than group D. There was no significant difference between group B[(303 +/- 13) kg/mm(2)] and group D[(294 +/- 23) kg/mm(2)]. At 120 um level, the microhardness value of group A was significantly higher than those of the other three groups. After the twice demineralization, the enamel surface microhardness value of the specimens was the same as the first measurement. In the cross-section at 40 um level, the microhardness value was equal to the value of cross-section at 80 um level of the first measurement. In the cross- section at 80 um and 120 um level, the microhardness value of group A was significantly higher than those of the other three groups. CONCLUSIONS: Resin infiltration can effectively strengthen microhardness of enamel surface and cross-section of different depth of artificial caries. PMID- 26887399 TI - [Effect of human papilloma virus infection status on the prognosis of localized stage head and neck squamous cell carcinomas in different ethnic groups of Xinjiang]. AB - OBJECTIVE: To discuss the effect of limited head and neck squamous cell carcinomas human papillomavirus(HPV) infection status on the prognosis in different nationalities of Xinjiang. METHODS: The clinical data of 149 cases of head and neck squamous cell carcinoma from Uighur, Han and Kazak was analyzed. The HPV16/18 infection and viral load was examined.The prognosis was analyzed by cox multiIvar-Iate model. The effect of HPV infection status on prognosis was evaluated. RESULTS: In this study, Oropharyngeal HPV infection rate was 35.0%, followed by hypopharynx 30.0%, oropharyx was 16.0%. The overall survival rate of 3 years and 5 years was 66.4%, and 39.2% respectively. The clinical stage,N stage and HPV were influencing factors for the prognosis of patients with head and neck squamous cell carcinoma (P< 0.05). N stage and HPV were independent prognostic factors for the prognosis of patients with head and neck squamous cell carcinoma (P< 0.05). CONCLUSIONS: There is a high rate of HPV infection in oropharynx in head and neck cancer. HPV positive is a protective factor for the prognosis of head and neck cancer, and the risk of death in patients with HPV was 3/5 lower than that of HPV negative patients. HPV viral load may be positively related to the total survival rate. N stage is a risk factor for the prognosis of head and neck cancer. Different nationalities have little influence on prognosis. PMID- 26887400 TI - [Analysis of type-I collagen fibrils and chondroitin sulfate distribution in human dentin by confocal laser scanning microscopy combined with dual immunofluorescent labeling technique]. AB - OBJECTIVE: To introduce the method of dual immunofluorescence labeling of human dentin matrix without demineralization of the whole dentin fragments, and to analyze the distribution of type-I collagen fibrils and chondroitin sulfate in human dentin. METHODS: Forty 30 um- thick middle coronal dentin sections were obtained from 8 freshly extracted human third molars and etched with 37% phosphoric acid(PA) gel for 15 s. After preconditioning with or without tosyl- phenylalanyl chloromethyl ketone(TPCK) treated trypsin digestion, sections were subjected to dual immunofluorescent labeling and scanned by confocal laser scanning microscopy to identify the type-I collagen fibrils and chondroitin sulfate. RESULTS: Chondroitin sulfate was localized in the lumens of the dentin tubules and peritubular dentin, while the type-I collagen fibrils were localized in intertubular dentin and peritubular dentin. After preconditioning with TPCK treated trypsin digestion, the red fluorescence was decreased or disappeared. CONCLUSIONS: The dual immunofluorescence labeling methodology can be used to study the human dentin matrix without demineralization of the whole dentin fragments. Chondroitin sulfate was localized in the lumens of the dentin tubules and peritubular dentin, while the type-I collagen fibrils were localized in intertubular dentin and peritubular dentin. PMID- 26887402 TI - [Application of piezotome and hydraulic pressure in crestal approach high inclination sinus floor elevation and simultaneous implant placement]. PMID- 26887401 TI - [Experimental study on the corrosion behavior of a type of oral near beta-type titanium alloys modified with double glow plasma nitriding]. AB - OBJECTIVE: To study the electrochemical corrosion performance of a type of biomedical materials near beta titanium alloy(Ti-3Zr-2Sn-3Mo-25Nb, TLM) in artificial saliva before and after nitride changing, and to provide clinical basis for clinical application of titanium alloy TLM. METHODS: The double glow plasma alloying technology was used to nitride the surface of titanium alloy TLM. The surface properties of the modified layer were observed and tested by optical microscope, scanning electron microscope, glow discharge spectrum analyzer, X-ray diffraction and micro hardness tester. Then, electrochemical measurement system was used to test and compare titanium alloy TLM's electrochemical corrosion in artificial saliva before and after its surface change. Finally, the surface morphology of the original titanium alloy and the modified layer was compared by scanning electron microscope. RESULTS: By the technology of double glow plasma nitriding, the surface of the titanium alloy TLM had been successfully nitrided with a modified layer of 4-5 um in thickness, uniform and compact. Its main compositions were Ti and Ti(2)N. The Microhardness of modified layer also had been improved from (236.8 +/- 5.4) to (871.8 +/- 5.2) HV. The self-corrosion potential in electrochemical corrosion tests had been increased from -0.559 V to 0.540 V, while the self- corrosion current density had been reduced from 2.091 * 10(-7) A/cm(2) to 7.188 * 10(-8) A/cm(2). Besides, alternating-current impedance(AC Impedance) had also been increased. With the scanning electron microscope, it's obvious that the diameter of corrosion holes on modified layer were approximately 10 um. As to the diameter and number of corrosion holes on modified layer, they had been decreased comparing with the original titanium alloy. CONCLUSIONS: The type of near beta titanium alloy TLM can construct a nitriding modified layer on its surface. Meanwhile, the performance of its anti- corrosion in artificial saliva has been improved, comparing to the original titanium alloy TLM. PMID- 26887403 TI - [Current advance in the development and application of zirconia implant]. PMID- 26887404 TI - [Relationship between nuclear factor-kappaB and oral carcinoma]. PMID- 26887405 TI - [Research and development of the autogenous tooth bone graft materia]. PMID- 26887406 TI - [A case of branchiogenic carcinoma]. PMID- 26887407 TI - Can roflumilast, a phosphodiesterase-4 inhibitor, improve clinical outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease? A meta analysis. AB - BACKGROUND: Effects of roflumilast on lung function, symptoms, acute exacerbation and adverse events in patients with chronic obstructive pulmonary disease (COPD) are controversial. We aimed to further clarify the efficacy and safety of roflumilast in treatment of moderate-to-severe COPD. METHODS: From 1946 to November 2015, we searched the Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials, ISI Web of Science and American College of Physician using "roflumilast" and "chronic obstructive pulmonary disease" or "COPD". Randomized controlled trials that reported forced expiratory volume in one second (FEV1), forced vital capacity (FVC), transition dyspnea index (TDI), St George's Respiratory Questionnaire (SGRQ), and incidence of COPD exacerbations and adverse events were eligible. We conducted the heterogeneities test and sensitivity analysis, and random-effects or fixed-effects model was applied to calculate risk ratio (RR) and mean difference (MD) for dichotomous and continuous data respectively. Cochrane systematic review software, Review Manager (RevMan), was used to test the hypothesis by Mann-Whitney U-test. RESULTS: Thirteen trials with a total of 14,563 patients were pooled in our final studies. Except for SGRQ (I (2) = 63 %, chi (2) = 1.71, P = 0.07) and adverse events (I (2) = 94 %, chi (2) = 0.03, P < 0.001), we did not find statistical heterogeneity in outcome measures. The pooled MD of pre- and post-bronchodilator FEV1 was 54.60 (95 % confidence interval (CI) 46.02 ~ 63.18) and 57.86 (95 % CI 49.80 ~ 65.91), and both showed significant improvement in patients with roflumilast (z = 12.47, P <0.001; z = 14.07, P < 0.001), so did in FVC (MD 90.37, 95 % CI 73.95 ~ 106.78, z = 10.79, P < 0.001). Significant alleviation of TDI (MD 0.30, 95 % CI 0.14 ~ 0.46, z = 3.67, P < 0.001) and decrease of acute exacerbation (RR 0.86, 95 % CI 0.81 ~ 0.91, z = 5.54, P < 0.001) were also identified in treatment of roflumilast, but without significant difference in SGRQ (MD -1.30, 95 % CI -3.16 ~ 0.56, z = 1.37, P = 0.17). Moreover, roflumilast significantly increased the incidence of adverse events compared with placebo (RR 1.31, 95 % CI 1.16 ~ 1.47, z = 4.32, P < 0.001). CONCLUSIONS: Roflumilast can be considered as an alternative therapy in selective patients with moderate-to-severe COPD. PMID- 26887410 TI - Loss. PMID- 26887408 TI - Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. AB - Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues. PMID- 26887411 TI - Blue Thought. PMID- 26887409 TI - Moramonas marocensis gen. nov., sp. nov.: a jakobid flagellate isolated from desert soil with a bacteria-like, but bloated mitochondrial genome. AB - A new jakobid genus has been isolated from Moroccan desert soil. The cyst-forming protist Moramonas marocensis gen. nov., sp. nov. has two anteriorly inserted flagella of which one points to the posterior cell pole accompanying the ventral feeding groove and is equipped with a dorsal vane-a feature typical for the Jakobida. It further shows a flagellar root system consisting of singlet microtubular root, left root (R1), right root (R2) and typical fibres associated with R1 and R2. The affiliation of M. marocensis to the Jakobida was confirmed by molecular phylogenetic analyses of the SSU rRNA gene, five nuclear genes and 66 mitochondrial protein-coding genes. The mitochondrial genome has the high number of genes typical for jakobids, and bacterial features, such as the four-subunit RNA polymerase and Shine-Dalgarno sequences upstream of the coding regions of several genes. The M. marocensis mitochondrial genome encodes a similar number of genes as other jakobids, but is unique in its very large genome size (greater than 264 kbp), which is three to four times higher than that of any other jakobid species investigated yet. This increase seems to be due to a massive expansion in non-coding DNA, creating a bloated genome like those of plant mitochondria. PMID- 26887412 TI - Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy. AB - Lacosamide is FDA-approved in patients 17 years or older with partial-onset epilepsy. We evaluated the efficacy and tolerability of lacosamide in children with refractory generalized epilepsy. We retrospectively reviewed records of 21 children with refractory generalized epilepsy treated with lacosamide in our institution from 2009-2013 divided into 2 subgroups- I, Lennox-Gastaut Syndrome, and II, other generalized epilepsies. Efficacy was defined as seizure freedom or >=50% seizure reduction. Descriptive data analysis including seizure freedom was compared using c(2) analysis. There were eleven females and ten males with a mean age, of 11.9 years. Five patients became seizure free, nine had >=50% seizure reduction, and seven had no response. Group I: seven had >=50% improvement, one did not respond. Group II: five became seizure free, two had >=50% improvement, five had no response. Lacosamide is effective and well tolerated in children with refractory generalized epilepsy particularly patients with Lennox-Gastaut Syndrome. PMID- 26887413 TI - Is Celiac Disease an Etiological Factor in Children With Migraine? AB - To determine the prevalence of celiac disease in children and adolescents with migraine, the authors investigated serum levels of tissue transglutaminase antibody immunoglobulin A and total immunoglobulin A from 81 children with migraine and in a healthy control group of 176 children. Study participants who were positive for tissue transglutaminase immunoglobulin A antibodies underwent a duodenal biopsy. Two patients in the migraine group (2.5%) and 1 in the control group (0.57%) tested positive for serum tissue transglutaminase immunoglobulin A antibodies (P > .05). Duodenal biopsy did not confirm celiac disease in both groups, and these patients were considered "potential celiac" cases. In the present study, children with migraine did not exhibit a higher prevalence rate of celiac disease compared with healthy controls. Therefore, the screening test for celiac disease is not a necessary part of the management of migraine in children. PMID- 26887414 TI - Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: a mixed studies systematic review. AB - BACKGROUND: The prime focus of research on sports injury has been on physical factors. This is despite our understanding that when an athlete sustains an injury it has psychosocial as well as physical impacts. Psychosocial factors have been suggested as prognostic influences on the outcomes of rehabilitation. The aim of this work was to address the question: are psychosocial factors associated with sports injury rehabilitation outcomes in competitive athletes? STUDY DESIGN: Mixed studies systematic review (PROSPERO reg.CRD42014008667). METHOD: Electronic database and bibliographic searching was undertaken from the earliest entry until 1 June 2015. Studies that included injured competitive athletes, psychosocial factors and a sports injury rehabilitation outcome were reviewed by the authors. A quality appraisal of the studies was undertaken to establish the risk of reporting bias. RESULTS: 25 studies were evaluated that included 942 injured competitive athletes were appraised and synthesised. Twenty studies had not been included in previous reviews. The mean methodological quality of the studies was 59% (moderate risk of reporting bias). Convergent thematic analysis uncovered three core themes across the studies: (1) emotion associated with rehabilitation outcomes; (2) cognitions associated with rehabilitation outcomes; and (3) behaviours associated with rehabilitation outcomes. Injury and performance related fears, anxiety and confidence were associated with rehabilitation outcomes. There is gender-related, age-related and injury-related bias in the reviewed literature. CONCLUSIONS: Psychosocial factors were associated with a range of sports injury rehabilitation outcomes. Practitioners need to recognise that an injured athlete's thoughts, feelings and actions may influence the outcome of rehabilitation. PMID- 26887415 TI - Muscle injury is the principal injury type and hamstring muscle injury is the first injury diagnosis during top-level international athletics championships between 2007 and 2015. AB - BACKGROUND: During top-level international athletics championships, muscle injuries are frequent. OBJECTIVE: To analyse the incidence and characteristics of muscle injuries and hamstring muscle injuries (hamstring injuries) occurring during top-level international athletics championships. METHODS: During 16 international championships held between 2007 and 2015, national medical team and local organising committee physicians reported daily all injuries on a standardised injury report form. Only muscle injuries (muscle tears and muscle cramps) and hamstring injuries have been analysed. RESULTS: 40.9% of all recorded injuries (n=720) were muscle injuries, with 57.5% of them resulting in time loss. The overall incidence of muscle injuries was higher in male athletes than female athletes (51.9+/-6.0 vs 30.3+/-5.0 injuries per 1000 registered athletes, respectively; RR=1.71; 95% CI 1.45 to 2.01). Muscle injuries mainly affected the thigh (52.9%) and lower leg (20.1%), and were mostly caused by overuse with sudden onset (38.2%) and non-contact trauma (24.6%). Muscle injury risk varied according to the event groups. Hamstring injuries represented 17.1% of all injuries, with a higher risk in male compared to female athletes (22.4+/-3.4 vs 11.5+/-2.6 injuries per 1000 registered athletes, respectively; RR=1.94; 95% CI 1.42 to 2.66). CONCLUSIONS: During international athletics championships, muscle injury is the principal type of injury, and among those, the hamstring is the most commonly affected, with a two times higher risk in male than female athletes. Athletes in explosive power events, male athletes and older male athletes, in specific were more at risk of muscle injuries and hamstring injuries. Injury prevention strategies should be sex-specific. PMID- 26887416 TI - Erratum to: NLK functions to maintain proliferation and stemness of NSCLC and is a target of metformin. PMID- 26887417 TI - Identification and characterization of thirty novel microsatellite DNA markers from the Chinese mitten crab Eriocheir sinensis expressed sequence tags. AB - BACKGROUND: The Chinese mitten crab Eriocheir sinensis is an economically important decapod crustacean in China. Despite a widespread distribution and production in China, the resources of E. sinensis have experienced a dramatic decline in the past decades. Here we describe a new set of novel polymorphic microsatellite loci to facilitate the investigation of genetic structure and artificial breeding. RESULTS: In this study, a set of 30 novel polymorphic microsatellite markers for E. sinensis was developed from EST databases. The number of alleles per locus ranged from three to twenty. The observed and expected heterozygosities ranged from 0.047 to 0.932 and from 0.047 to 0.935, respectively. CONCLUSIONS: These informative microsatellite markers will be useful in studies of genetics, genomics and marker-assisted selection breeding in E. sinensis. PMID- 26887418 TI - Tryptophan depletion in context of the inflammatory and general nutritional status of a low-income South African HIV-infected population. AB - BACKGROUND: The essential amino acid tryptophan cannot be synthesised in the body and must be acquired through dietary intake. Oxidation of tryptophan, due to immune induction of the enzyme indoleamine 2,3-dioxygenase (IDO), is considered to be the main cause of tryptophan depletion in HIV infection and AIDS. We examined plasma tryptophan levels in a low-income sub-Saharan HIV-infected population and compared it to that of developed countries. Tryptophan levels were further examined in context of the general nutritional and inflammatory status. METHODS: This cross-sectional study included 105 HIV-positive patients recruited from the Kalafong Hospital in Pretoria, South Africa, and 60 HIV-negative controls. RESULTS: Patient tryptophan levels were in general markedly lower than those reported for developed countries. In contrast to reports from developed countries that showed tryptophan levels on average to be 18.8 % lower than their control values, tryptophan levels in our study were 44.1 % lower than our controls (24.4 +/- 4.1 vs. 43.6 +/- 11.9 MUmol/l; p < 0.001). Tryptophan levels correlated with both CD4 counts (r = 0.341; p = 0.004) and with pro-inflammatory activity as indicated by neopterin levels (r = -0.399; p = 0.0001). Nutritional indicators such as albumin and haemoglobin correlated positively with tryptophan and negatively with the pro-inflammatory indicators neopterin, interleukin 6 and C-reactive protein. The most probable causes of the lower tryptophan levels seen in our population are food insecurity and higher levels of inflammatory activity. CONCLUSIONS: We contend that inflammation-induced tryptophan depletion forms part of a much wider effect of pro-inflammatory activity on the nutritional profile of HIV-infected patients. PMID- 26887419 TI - The relationship between serum fatty-acid binding protein 4 level and lung function in Korean subjects with normal ventilatory function. AB - BACKGROUND: The aim of this study was to assess the association of lung function with serum fatty-acid binding protein 4 (FABP4) in apparently healthy Korean adults. METHODS: In 495 participants in a health screening program, Force Exploratory Volume (FEV) 1 and Forced Vital Capacity (FVC) were assessed with standard spirometry. Subjects with obstructive (n = 19) and restrictive (n = 45) lung function were excluded from the analysis. Serum FABP4 level was measured by enzyme-linked immunosorbent assay and transformed into Ln(FABP4). 431 subjects with normal ventilator function (72.4% men, mean age 41 years) were included in the final analysis. RESULTS: Mean Ln(FABP4) significantly decreased in subjects from 1(st) quartile to 4(th) quartile of FVC (p = 0.008). Ln(FABP4) did not show significant differences across the quartile groups of FEV1. The odds ratio (OR) of being in the lowest quartile of FVC was 2.704 in subject with 3(rd) tertile of Ln(FABP4) after full adjustment for confounding variables {95% confidence interval (CI) 1.397 ~ 5.357}. OR of being in the lowest quartile of FEV1 was 1.822 (95% CI 1.021 ~ 3.298) in subjects with 3(rd) tertile of Ln(FABP4) after adjustment of age and sex, which was attenuated after full adjustment for confounding variables. CONCLUSION: Increased FABP4 level showed increased risk for reduced lung function in subjects with normal ventilatory function. PMID- 26887421 TI - Appropriate design, methodological quality assessment, and clinically relevant outcomes are essential to determine the therapeutic role of epidural injections for low back pain and radiculopathy. PMID- 26887420 TI - Effects of naturopathic medicines on Multiplate and ROTEM: a prospective experimental pilot study in healthy volunteers. AB - BACKGROUND: Of patients undergoing surgery, 22 to 57% have been reported to be using naturopathic medicines. Several of these medicines have been reported to increase bleeding or enhance the effect of other drugs that increase bleeding. The Swedish Medical Products Agency recommends cessation of the use of the naturopathic medicines echinacea, fish oil, ginkgo biloba, ginseng, St. John's wort, valeriana and garlic 2 weeks before surgery. The aim of this pilot study was to examine the effects of these 7 naturopathic medicines in healthy humans by utilising multiple electrode aggregometer (Multiplate) and viscoelastic rotational thromboelastometer (ROTEM) to obtain data for sample size calculation before a larger trial. METHODS: Thirty-five healthy volunteers ingested one of the listed naturopathic medicines for 7 days. Each naturopathic medicine was taken in a recommended standard dose by 5 volunteers. ROTEM clot initiation (CT), clot formation (CFT), alpha-angle (AA) and clot structure (MCF) were analysed with tissue factor activated (EXTEM) and native (NATEM) assays. The Multiplate platelet aggregation area under curve (AUC) was measured with adenosine diphosphate (ADP), collagen (COL) and arachidonic acid (ASPI) assays. RESULTS: Multiplate with ADP agonist decreased from 73 +/- 8.7 AUC to 60 +/- 5.9 AUC (P = 0.003, 95% confidence interval (CI) -19.2 to -7.6) after medication with fish oil, but fish oil had no effect on COL or ASPI reagents. None of the other naturopathic medicines had any effect on Multiplate aggregometry. ROTEM NATEM-CFT increased from 217 +/- 32 s to 283 +/- 20 (P = 0.009, 95% CI 26.8 to 107), and NATEM-AA decreased from 52 +/- 3.9 degrees to 44 +/- 2.3 degrees (P = 0.009, 95 % CI -12.0 to -3.2) after medication with fish oil. There were no significant changes in the other NATEM or EXTEM parameters. The other naturopathic medicines had no significant effects on ROTEM or Multiplate aggregometry. CONCLUSIONS: We have demonstrated that a recommended standard intake of 1260 mg Omega-3 polyunsaturated fatty acids (fish oil) daily - but not echinacea, ginkgo biloba, ginseng, St. John's wort, valeriana or garlic - may decrease platelet aggregation and clot formation. A larger trial in this setting would be meaningful to perform. TRIAL REGISTRATION: Trial registration ISRCTN78027929. Registered 19 May 2015. PMID- 26887422 TI - Cardiac resynchronisation therapy with an implantable cardioverter defibrillator appears to be cost-effective in patients with mild heart failure. PMID- 26887423 TI - Insomnia is associated with risk of future cardiovascular events irrespective of comorbidities. PMID- 26887424 TI - Both paroxetine and imipramine appear to be ineffective in adolescents with major depression, furthermore doubts have risen about their safety. PMID- 26887425 TI - JAK inhibitors truly changing the therapeutic paradigm in myelofibrosis. PMID- 26887426 TI - Adenosine Triphosphate Regresses Endometrial Explants in a Rat Model of Endometriosis. AB - The aim of this study was to determine the effects of adenosine triphosphate (ATP) in a rat endometriosis model. After surgical induction of endometriosis, 3 rats were killed, and explants were measured in the remaining 19 rats, which were then randomly assigned to 4 groups. Group 1 (n = 4) received normal saline (2 mL/d intragastric [IG]), group 2 (n = 4) gestrinone (0.5 mg/kg/d IG), group 3 (n = 5) ATP (3.4 mg/kg/d IG), and group 4 (n = 6) ATP (1.0 mg/kg/d; intramuscularly), respectively. Four weeks after medication, they were euthanized to evaluate histological features of explants and eutopic uterine tissues. To test the effect of ATP on the growth of eutopic endometrium stromal cells, proliferation rates of hEM15A cells at 24, 48, and 72 hours after treatment with different concentrations of ATP and vehicle control were detected with the Cell Counting Kit-8 (CCK-8) method. There was a significant difference between pretreatment and posttreatment volumes within group 2 (positive control; P = .048) and group 4 (P = .044). On condition that pretreatment implant size was similar in both groups (P = .516), regression of explants in group 4 was significantly higher than that in group 1 (negative control; P = .035). Epithelial cells were significantly better preserved in group 1 than in group 3 (P = .008) and group 4 (P = .037). The CCK-8 assay showed no significant difference in proliferation among hEM15A cells treated with ATP and controls. These results suggest that ATP regresses endometriotic tissues in a rat endometriosis model but has no impact on the growth of eutopic endometrium stromal cells. PMID- 26887427 TI - Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis. AB - Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29). Plasma levels of endocannabinoids (N-arachidonoylethanolamine [AEA] and 2 arachidonoylglycerol [2-AG]) and related mediators (N-oleoylethanolamine [OEA] and N-palmitoylethanolamine [PEA]), messenger RNA expression of some of their receptors (cannabinoid receptor type 1 [CB1], CB2, transient receptor potential vanilloid type [TRPV1]), and the enzymes involved in the synthesis (N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D [NAPE-PLD]) and degradation (fatty acid amide hydrolase 1 [FAAH]) of AEA, OEA, and PEA were evaluated in endometrial stromal cells. The systemic levels of AEA, 2-AG, and OEA were elevated in endometriosis in the secretory phase compared to controls. The expression of CB1 was higher in secretory phase endometrial stromal cells of controls versus endometriosis. Similar expression levels of CB2, TRPV1, NAPE-PLD, and FAAH were detected in controls and endometriosis. Patients with moderate-to severe dysmenorrhea and dyspareunia showed higher AEA and PEA levels than those with low-to-moderate pain symptoms, respectively. The association of increased circulating AEA and 2-AG with decreased local CB1 expression in endometriosis suggests a negative feedback loop regulation, which may impair the capability of these mediators to control pain. These preliminary data suggest that the pharmacological manipulation of the action or levels of these mediators may offer an alternative option for the management of endometriosis-associated pain. PMID- 26887428 TI - Effect of Human Umbilical Cord Mesenchymal Stem Cell Transplantation in a Rat Model of Preeclampsia. AB - OBJECTIVE: To test the effects of human umbilical cord mesenchymal stem cell (HU MSC) transplantation on reversing preeclampsia (PE) symptoms in a lipopolysaccharide (LPS)-induced rat PE model. METHODS: Human umbilical cord MSCs were detected, isolated, and cultured. Human umbilical cord MSC transplantation was conducted. Expressions of inflammatory cytokines in serum and placental tissue were measured by enzyme-linked immunosorbent assay. Changes in inflammatory cytokines, peroxisome proliferator-activated receptor gamma (PPARgamma), laminin receptor 1 (LR1), matrix metalloproteinase (MMP) 2, and MMP 9 messenger RNA (mRNA) levels in placental tissue were recorded by quantitative real-time polymerase chain reaction. Immunohistochemistry and Western blotting were performed for PPARgamma detection. RESULTS: The LPS group exhibited increased blood pressure and proteinuria and decreased fetal weight compared to the normal pregnancy (NP) group (all P < .05). The LPS + MSC group presented lowered blood pressure and higher fetal weight than the LPS group (P < .05). The levels of interferon gamma, tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IL-8, IL-12, and intercellular adhesion molecule 1 (ICAM-1) increased and the levels of IL-4 and IL-10 levels decreased in the LPS group compared to the NP group (all P < .05). Tumor necrosis factor alpha, IL-6, IL-12, and ICAM-1 levels decreased and IL-10 level increased in the LPS + MSC group compared to the LPS group (all P < .05). The LPS-MSC group showed lower mRNA expressions of TNF-alpha, IL-6, MMP-2, MMP-9, and ICAM-1 and higher mRNA expressions of IL-10, PPARgamma, and LR1 than the LPS group (all P < .05). CONCLUSION: In summary, HU-MSC transplantation may be extremely beneficial for PE therapy. PMID- 26887429 TI - Probing the Buried Magnetic Interfaces. AB - Understanding magnetism in ferromagnetic metal/semiconductor (FM/SC) heterostructures is important to the development of the new-generation spin field effect transistor. Here, we report an element-specific X-ray magnetic circular dichroism study of the interfacial magnetic moments for two FM/SC model systems, namely, Co/GaAs and Ni/GaAs, which was enabled using a specially designed FM1/FM2/SC superstructure. We observed a robust room temperature magnetization of the interfacial Co, while that of the interfacial Ni was strongly diminished down to 5 K because of hybridization of the Ni d(eg) and GaAs sp(3) states. The validity of the selected method was confirmed by first-principles calculations, showing only small deviations (<0.02 and <0.07 MUB/atom for Co/GaAs and Ni/GaAs, respectively) compared to the real FM/SC interfaces. Our work proved that the electronic structure and magnetic ground state of the interfacial FM2 is not altered when the topmost FM2 is replaced by FM1 and that this model is applicable generally for probing the buried magnetic interfaces in the advanced spintronic materials.. PMID- 26887430 TI - Measuring redox-active species in cells and tissues. Focus on "A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?". PMID- 26887431 TI - Development of ovine chorionic somatomammotropin hormone-deficient pregnancies. AB - Intrauterine growth restriction (IUGR) is a leading cause of neonatal mortality and morbidity. Chorionic somatomammotropin hormone (CSH), a placenta-specific secretory product found at high concentrations in maternal and fetal circulation throughout gestation, is significantly reduced in human and sheep IUGR pregnancies. The objective of this study was to knock down ovine CSH (oCSH) expression in vivo using lentiviral-mediated short-hairpin RNA to test the hypothesis that oCSH deficiency would result in IUGR of near-term fetal lambs. Three different lentiviral oCSH-targeting constructs were used and compared with pregnancies (n = 8) generated with a scrambled control (SC) lentiviral construct. Pregnancies were harvested at 135 days of gestation. The most effective targeting sequence, "target 6" (tg6; n = 8), yielded pregnancies with significant reductions (P <= 0.05) in oCSH mRNA (50%) and protein (38%) concentrations, as well as significant reductions (P <= 0.05) in placental (52%) and fetal (32%) weights compared with the SC pregnancies. Fetal liver weights were reduced 41% (P <= 0.05), yet fetal liver insulin-like growth factor-I (oIGF1) and -II mRNA concentrations were reduced (P <= 0.05) 82 and 71%, respectively, and umbilical artery oIGF1 concentrations were reduced 62% (P <= 0.05) in tg6 pregnancies. Additionally, fetal liver oIGF-binding protein (oIGFBP) 2 and oIGFBP3 mRNA concentrations were reduced (P <= 0.05), whereas fetal liver oIGFBP1 mRNA concentration was not impacted nor was maternal liver oIGF and oIGFBP mRNA concentrations or uterine artery oIGF1 concentrations (P >= 0.10). Based on our results, it appears that oCSH deficiency does result in IUGR, by impacting placental development as well as fetal liver development and function. PMID- 26887432 TI - Voluntary wheel running attenuates lipopolysaccharide-induced liver inflammation in mice. AB - Sepsis induces an acute inflammatory response in the liver, which can lead to organ failure and death. Given the anti-inflammatory effects of exercise, we hypothesized that habitual physical activity could protect against acute sepsis induced liver inflammation via mechanisms, including heat shock protein (HSP) 70/72. Male C57BL/6J mice (n = 80, ~8 wk of age) engaged in physical activity via voluntary wheel running (VWR) or cage control (SED) for 10 wk. To induce sepsis, we injected (2 mg/kg ip) LPS or sterile saline (SAL), and liver was harvested 6 or 12 h later. VWR attenuated increases in body and epididymal adipose tissue mass, improved glucose tolerance, and increased liver protein content of PEPCK (P < 0.05). VWR attenuated increases in LPS-induced IL-6 signaling and mRNA expression of other inflammatory markers (TNF-alpha, chemokine C-C motif ligand 2, inducible nitric oxide synthase, IL-10, IL-1beta) in the liver; however, this was not reflected at the whole body level, as systemic markers of inflammation were similar between SED and VWR. Insulin tolerance was greater in VWR compared with SED at 6 but not 12 h after LPS. The protective effect of VWR occurred in parallel with increases in the liver protein content of HSP70/72, a molecular chaperone that can protect against inflammatory challenges. This study provides novel evidence that physical activity protects against the inflammatory cascade induced by LPS in the liver and that these effects may be mediated via HSP70/72. PMID- 26887433 TI - Factors related to fatigue in Chinese patients with end-stage renal disease receiving maintenance hemodialysis: a multi-center cross-sectional study. AB - BACKGROUD: Fatigue is considered as a common symptom in patients with end-stage renal disease (ESRD) and can significantly decrease patients' quality of life. This study aimed to assess fatigue in hemodialysis patients and to investigate risk factors of fatigue in Chinese patients receiving maintenance hemodialysis (MHD) in China. METHODS: Eligible patients completed questionnaires including demographic information, a Chinese version of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), the Family APGAR Index (APGAR), the medical outcomes study health status-Social Functioning subscale (SF 36,SocF), and the Pittsburgh sleep quality index (PSQI). Laboratory parameters were abstracted by medical records review. The multiple linear regression model was used to relate parameters with the FACIT-Fatigue score. RESULTS: A total of 345 MHD patients (216 men and 129 women, age 55.6 +/- 12.8) were recruited in this study. The score of FACIT-Fatigue was 39 (Interquartile Range, 31-44). Fatigue was correlated with PSQI scores (p < 0.001), SocF scores (p < 0.001), comorbidity (p = 0.006), exercise time <1 hour per day (p = 0.003), adequacy of dialysis (Kt/V) < 1.2 (p = 0.016), APGAR scores (p = 0.014), and high Scr (p = 0.043). CONCLUSIONS: Fatigue is related to sleep disturbance, social and family functioning, taking physical exercise time, comorbidity condition, Kt/V and serum creatinine level in Chinese MHD patients. Future studies and interventions should focus on developing strategies and improving the quality of life in patients by addressing these significant contributing factors. PMID- 26887434 TI - Gastric varicella: two cases in cancer patients. AB - Gastric involvement with the varicella-zoster virus is an uncommon clinical condition where early suspicion and diagnosis are important to prevent the consequences deriving from its high morbidity and mortality, which in immunocompromised patients oscillate between 9% and 41% according to the various series. Two cases of gastric involvement with the varicella-zoster virus (VZV) in two patients with blood cancer are reported below. Gastric lesions are usually preceded by typical papulovesicular skin lesions. When gastric involvement is the first symptom of the disease its diagnosis and management may be delayed, which may entail severe consequences for immunocompromised patients. It is therefore that we suggest its inclusion in the algorithm for immunocompromised patients with abdominal pain and ulcer-like endoscopic lesions. PMID- 26887435 TI - Relapsing polychondritis complicated by cognitive dysfunction: two distinct clinical phenotypes? AB - Relapsing polychondritis (RPC) is a rare, immune-mediated condition affecting approximately 3.5 per million population per year. Neurological involvement in RPC is still rarer and is presumed to be the result of a vasculitic process, although this is seldom confirmed in the literature. We present two cases of RPC complicated by cognitive dysfunction with contrasting clinical trajectories. Our findings suggest that there are two clinical phenotypes of cognitive dysfunction in RPC. The first is a fulminant, multisystem presentation with sub-acute cognitive decline mimicking central nervous system vasculitis, and we provide histopathological evidence of this process occurring. The other is an insidious cognitive decline without associated constitutional or systemic symptoms. PMID- 26887436 TI - CellECT: cell evolution capturing tool. AB - BACKGROUND: Robust methods for the segmentation and analysis of cells in 3D time sequences (3D+t) are critical for quantitative cell biology. While many automated methods for segmentation perform very well, few generalize reliably to diverse datasets. Such automated methods could significantly benefit from at least minimal user guidance. Identification and correction of segmentation errors in time-series data is of prime importance for proper validation of the subsequent analysis. The primary contribution of this work is a novel method for interactive segmentation and analysis of microscopy data, which learns from and guides user interactions to improve overall segmentation. RESULTS: We introduce an interactive cell analysis application, called CellECT, for 3D+t microscopy datasets. The core segmentation tool is watershed-based and allows the user to add, remove or modify existing segments by means of manipulating guidance markers. A confidence metric learns from the user interaction and highlights regions of uncertainty in the segmentation for the user's attention. User corrected segmentations are then propagated to neighboring time points. The analysis tool computes local and global statistics for various cell measurements over the time sequence. Detailed results on two large datasets containing membrane and nuclei data are presented: a 3D+t confocal microscopy dataset of the ascidian Phallusia mammillata consisting of 18 time points, and a 3D+t single plane illumination microscopy (SPIM) dataset consisting of 192 time points. Additionally, CellECT was used to segment a large population of jigsaw-puzzle shaped epidermal cells from Arabidopsis thaliana leaves. The cell coordinates obtained using CellECT are compared to those of manually segmented cells. CONCLUSIONS: CellECT provides tools for convenient segmentation and analysis of 3D+t membrane datasets by incorporating human interaction into automated algorithms. Users can modify segmentation results through the help of guidance markers, and an adaptive confidence metric highlights problematic regions. Segmentations can be propagated to multiple time points, and once a segmentation is available for a time sequence cells can be analyzed to observe trends. The segmentation and analysis tools presented here generalize well to membrane or cell wall volumetric time series datasets. PMID- 26887438 TI - Small-molecule PSMA ligands. Current state, SAR and perspectives. AB - Prostate cancer (PC) is the prevalent malignancy widespread among men in the Western World. Prostate specific membrane antigen (PSMA) is an established PC marker and has been considered as a promising biological target for anti-PC drug delivery and diagnostics. The protein was found to be overexpressed in PC cells, including metastatic, and the neovasculature of solid tumors. These properties make PSMA-based approach quite appropriate for effective PC imaging and specific drug therapy. Through the past decade, a variety of PSMA-targeted agents has been systematically evaluated. Small-molecule compounds have several advantages over other classes, such as improved pharmacokinetics and rapid blood clearance. These low-weight ligands have similar structure and can be divided into three basic categories in accordance with the type of their zinc-binding core-head. Several PSMA binders are currently undergoing clinical trials generally for PC imaging. The main goal of the present review is to describe the recent progress achieved within the title field and structure activity relationships (SAR) disclosed for different PSMA ligands. Recent in vitro and in vivo studies for each type of the compounds described have also been briefly summarized. PMID- 26887439 TI - Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids. AB - The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by dietary consumption of fatty acids such as saturated fatty acids and polyunsaturated fatty acids (PUFAs). Cells must adapt to changes in composition of membrane fatty acids by regulating lipid-metabolizing enzymes. In this study, we investigated how cells respond to loading with excess PUFAs, such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. A lipidomics analysis revealed that dipalmitoylphosphatidylcholine (DPPC) was increased after the production of PUFA containing phospholipids in cells loaded with PUFAs. An RNA interference screen of lipid-metabolizing enzymes revealed that lysophosphatidylcholine acyltransferase 1 (LPCAT1) was involved in the DPPC production. Moreover, LPCAT1 knockdown markedly enhanced the cytotoxicity induced by excess PUFAs. PUFA induced cytotoxicity was dependent on caspase and unfolded protein response (UPR) sensor proteins inositol requiring 1alpha and protein kinase R-like endoplasmic reticulum kinase, suggesting that excess PUFAs trigger UPR-mediated apoptosis. In murine retina, in which PUFAs are highly enriched, DPPC was produced along with increase of PUFA-containing phospholipids. In LPCAT1 knockout mice, DPPC level was reduced and UPR was activated in the retina. Our results provide insight into understanding of the retinal degeneration seen in rd11 mice that lack LPCAT1. Akagi, S., Kono, N., Ariyama, H., Shindou, H., Shimizu, T., Arai, H. Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids. PMID- 26887440 TI - Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD. AB - We investigated changes in gene expression that occur in chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms that regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I to II) before and after treatment with fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene expression was measured by microarray and was confirmed by real-time reverse transcription-quantitative PCR (RT-qPCR). The effect of FP on IgG expression and B-cell proliferation in the presence of oxidative stress was also studied. FP/SM significantly increased the expression of 180 genes while repressing 343 genes. The top 5 down-regulated genes were associated with immunoglobulin production, whereas the immunomodulatory FK506 binding protein (FK506BP) was up-regulated. Genes including IL6, IL8, and TBET-encoding TBX21 were unaffected. FP reduced IgG protein and mRNA expression and proliferation of human B cells through the dephosphorylation of ERK-1/2 via increased DUSP1 (dual specificity protein phosphatase 1) expression. Consistent with in vivo data, oxidative stress did not prevent FP-induced suppression of IgG expression in human B cells in vitro Changes in expression were validated by RT-qPCR and by gene set enrichment analysis in distinct COPD cohorts. FP may reduce the adaptive immune response in COPD and may be more effective in patients with an increased B cell/antibody response indicated by high autoantibody titers.-Lee, J., Machin, M., Russell, K. E., Pavlidis, S., Zhu, J., Barnes, P. J., Chung, K. F., Adcock, I. M., Durham, A. L. Corticosteroid modulation of immunoglobulin expression and B cell function in COPD. PMID- 26887441 TI - MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. AB - The mechanism of blood-brain barrier (BBB) disruption, involved in poststroke edema and hemorrhagic transformation, is important but elusive. We investigated microRNA-150 (miR-150)-mediated mechanism in the disruption of BBB after stroke in rats. We found that up-regulation of miR-150 increased permeability of BBB as detected by MRI after permanent middle cerebral artery occlusion in vivo as well as increased permeability of brain microvascular endothelial cells after oxygen glucose deprivation in vitro. The expression of claudin-5, a key tight junction protein, was decreased in the ischemic boundary zone after up-regulation of miR 150. We found in brain microvascular endothelial cells that overexpression of miR 150 decreased not only cell survival rate but also the expression levels of claudin-5 after oxygen-glucose deprivation. With dual-luciferase assay, we confirmed that miR-150 could directly regulate the angiopoietin receptor Tie-2. Moreover, silencing Tie-2 with lentivirus-delivered small interfering RNA reversed the effect of miR-150 on endothelial permeability, cell survival, and claudin-5 expression. Furthermore, poststroke treatment with antagomir-150, a specific miR-150 antagonist, contributed to BBB protection, infarct volume reduction, and amelioration of neurologic deficits. Collectively, our findings suggested that miR-150 could regulate claudin-5 expression and endothelial cell survival by targeting Tie-2, thus affecting the permeability of BBB after permanent middle cerebral artery occlusion in rats, and that miR-150 might be a potential alternative target for the treatment of stroke.-Fang, Z., He, Q.-W., Li, Q., Chen, X.-L., Baral, S., Jin, H.-J., Zhu, Y.-Y., Li, M., Xia, Y.-P., Mao, L., Hu, B. MicroRNA-150 regulates blood-brain barrier permeability via Tie-2 after permanent middle cerebral artery occlusion in rats. PMID- 26887442 TI - Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover. AB - We studied the physiologic roles of the hyaluronidase (HYAL) 1 and HYAL2 in hyaluronan (HA) turnover. HA was localized and quantified using HA binding proteins in various tissues of Hyal1(-/-) and Hyal2(-/-) mice (knockout mice) as well as control mice. HA MW was determined using gel filtration chromatography. HA endocytosis in liver nonparenchymal cells (NPCs) was quantified in vivo Both Hyal1 and Hyal2 knockout mice showed HA accumulation in peripheral tissues without changes in HA MW distribution. HYAL2 deficiency induced buildup of very high MW (>3.10(6) Da) HA in lymph and serum with severe lymph node distortion. The lack of HYAL2 also impaired high MW HA endocytosis by liver NPCs. HYAL1 deficiency led to a moderate increase in serum HA concentration without changes in HA MW distribution and to HA overload of liver NPCs. Wild-type C57BL/6 mice served as controls. In HA injection experiments, saline-injected mice served as additional controls. We conclude that: 1) HYAL1 and HYAL2 are both needed for tissue HA catabolism; 2) HYAL2 is required for high MW HA clearance in lymph nodes and plasma and for HA endocytosis by liver NPCs; and 3) the main role of HYAL1 is HA degradation within liver NPCs.-Bourguignon, V., Flamion, B. Respective roles of hyaluronidases 1 and 2 in endogenous hyaluronan turnover. PMID- 26887443 TI - Hypoxic HepG2 cell adaptation decreases ATP synthase dimers and ATP production in inflated cristae by mitofilin down-regulation concomitant to MICOS clustering. AB - The relationship of the inner mitochondrial membrane (IMM) cristae structure and intracristal space (ICS) to oxidative phosphorylation (oxphos) is not well understood. Mitofilin (subunit Mic60) of the mitochondrial contact site and cristae organizing system (MICOS) IMM complex is attached to the outer membrane (OMM) via the sorting and assembly machinery/topogenesis of mitochondrial outer membrane beta-barrel proteins (SAM/TOB) complex and controls the shape of the cristae. ATP synthase dimers determine sharp cristae edges, whereas trimeric OPA1 tightens ICS outlets. Metabolism is altered during hypoxia, and we therefore studied cristae morphology in HepG2 cells adapted to 5% oxygen for 72 h. Three dimensional (3D), super-resolution biplane fluorescence photoactivation localization microscopy with Eos-conjugated, ICS-located lactamase-beta indicated hypoxic ICS expansion with an unchanged OMM (visualized by Eos-mitochondrial fission protein-1). 3D direct stochastic optical reconstruction microscopy immunocytochemistry revealed foci of clustered mitofilin (but not MICOS subunit Mic19) in contrast to its even normoxic distribution. Mitofilin mRNA and protein decreased by ~20%. ATP synthase dimers vs monomers and state-3/state-4 respiration ratios were lower during hypoxia. Electron microscopy confirmed ICS expansion (maximum in glycolytic cells), which was absent in reduced or OMM detached cristae of OPA1- and mitofilin-silenced cells, respectively. Hypoxic adaptation is reported as rounding sharp cristae edges and expanding cristae width (ICS) by partial mitofilin/Mic60 down-regulation. Mitofilin-depleted MICOS detaches from SAM while remaining MICOS with mitofilin redistributes toward higher interdistances. This phenomenon causes partial oxphos dormancy in glycolytic cells via disruption of ATP synthase dimers.-Plecita-Hlavata, L., Engstova, H., Alan, L., Spacek, T., Dlaskova, A., Smolkova, K., Spackova, J., Tauber, J., Stradalova, V., Malinsky, J., Lessard, M., Bewersdorf, J., Jezek, P. Hypoxic HepG2 cell adaptation decreases ATP synthase dimers and ATP production in inflated cristae by mitofilin down-regulation concomitant to MICOS clustering. PMID- 26887444 TI - Manipulating the interfacial structure of nanomaterials to achieve a unique combination of strength and ductility. AB - The control of interfaces in engineered nanostructured materials has met limited success compared with that which has evolved in natural materials, where hierarchical structures with distinct interfacial states are often found. Such interface control could mitigate common limitations of engineering nanomaterials. For example, nanostructured metals exhibit extremely high strength, but this benefit comes at the expense of other important properties like ductility. Here, we report a technique for combining nanostructuring with recent advances capable of tuning interface structure, a complementary materials design strategy that allows for unprecedented property combinations. Copper-based alloys with both grain sizes in the nanometre range and distinct grain boundary structural features are created, using segregating dopants and a processing route that favours the formation of amorphous intergranular films. The mechanical behaviour of these alloys shows that the trade-off between strength and ductility typically observed for metallic materials is successfully avoided here. PMID- 26887445 TI - Organic heterojunctions: Contact-induced molecular reorientation, interface states, and charge re-distribution. AB - We reveal the rather complex interplay of contact-induced re-orientation and interfacial electronic structure - in the presence of Fermi-level pinning - at prototypical molecular heterojunctions comprising copper phthalocyanine (H16CuPc) and its perfluorinated analogue (F16CuPc), by employing ultraviolet photoelectron and X-ray absorption spectroscopy. For both layer sequences, we find that Fermi level (EF) pinning of the first layer on the conductive polymer substrate modifies the work function encountered by the second layer such that it also becomes EF-pinned, however, at the interface towards the first molecular layer. This results in a charge transfer accompanied by a sheet charge density at the organic/organic interface. While molecules in the bulk of the films exhibit upright orientation, contact formation at the heterojunction results in an interfacial bilayer with lying and co-facial orientation. This interfacial layer is not EF-pinned, but provides for an additional density of states at the interface that is not present in the bulk. With reliable knowledge of the organic heterojunction's electronic structure we can explain the poor performance of these in photovoltaic cells as well as their valuable function as charge generation layer in electronic devices. PMID- 26887446 TI - Guidelines for Performing Dermatologic Ultrasound Examinations by the DERMUS Group. AB - OBJECTIVES: To support standardization for performing dermatologic ultrasound examinations. METHODS: An international working group, called DERMUS (Dermatologic Ultrasound), was formed, composed of physicians who have been working on a regular basis and publishing in peer-reviewed articles on dermatologic ultrasound. A questionnaire on 5 critical issues about performance of the examinations was prepared and distributed by e-mail. The areas of discussion included technical aspects, main areas of application, minimum number of examinations per year required for assessing competence, qualifications of the personnel in charge of the examination, and organization of courses. Final recommendations were approved on the basis of the agreement of more than 50% of the members. RESULTS: The minimum frequency recommended for performing dermatologic examinations was 15 MHz. Routine use of color Doppler ultrasound and the performance of spectral curve analysis for assessing the main vascularity of lesions were suggested. Three-dimensional reconstructions were considered optional. The main dermatologic applications were benign tumors, skin cancer, vascular anomalies, cosmetic field, nail disorders, and inflammatory diseases. The minimum number of examinations per year suggested by the group for assessing competence was 300. A physician and not a sonographer was recommended to be the person in charge of performing the examination. On course organization, a minimum of 2 levels of complexity (basic and advanced) was suggested. CONCLUSIONS: There is a need to standardize the performance and quality of dermatologic ultrasound examinations. The present guidelines written by an international group of specialists in the field may support this objective. PMID- 26887447 TI - Evaluation of Underlying Lymphocytic Thyroiditis With Histogram Analysis Using Grayscale Ultrasound Images. AB - OBJECTIVES: The purpose of this study was to evaluate diagnostic performance of histogram analysis using grayscale ultrasound (US) images in the diagnosis of lymphocytic thyroiditis. METHODS: Three radiologists reviewed a total of 505 US images and classified the images according to the presence/existence of lymphocytic thyroiditis. After 2 months, each reviewer repeated the process with the same 505 images in a randomly mixed order. The intraobserver and interobserver variability was analyzed with a generalized kappa value. Four histogram parameters (mean value, standard deviation, skewness, and kurtosis) were obtained, and an index was calculated from principal component analysis. Diagnostic performances were compared. RESULTS: Of 505 patients, 125 (24.8%) had lymphocytic thyroiditis, and 380 (75.2%) had normal thyroid parenchyma on pathologic analysis. The kappa value for intraobserver variance ranged from 0.002 to 0.781, and the overall kappa values for interobserver variance were 0.570 and 0.214 in the first and second tests, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for the 3 reviewers versus the principal component analysis index were 28.0% to 83.2%, 43.7% to 82.6%, 53.5% to 79.0%, 24.6% to 56.2%, and 75.2% to 88.9% versus 58.4%, 72.4%, 68.9%, 41.0%, and 84.1%. CONCLUSIONS: Histogram analysis of grayscale US images provided confirmable and quantitative information about lymphocytic thyroiditis and was comparable with performers' assessments in diagnostic performance. PMID- 26887448 TI - Damage Effects on Bacille Calmette-Guerin by Low-Frequency, Low-Intensity Ultrasound: A Pilot Study. AB - OBJECTIVES: To perform an in vitro experimental study of the possible damage effects on Bacille Calmette-Guerin (BCG) by low-frequency (42-kHz) ultrasound (US) irradiation at low spatially and temporally averaged intensities and different exposure times. METHODS: A 2-mL BCG suspension was added to the wells of a 24-well cell culture plate. Then the samples were randomly divided into 4 groups, each group including 3 wells, with group 1 as a control group and groups 2, 3, and 4, as US treatment groups. The samples for groups 2, 3, and 4 were irradiated with US at 0.13 W/cm(2) for 5 minutes, 0.13 W/cm(2) for 15 minutes, and 1.53 W/cm(2) for 15 minutes, respectively. After irradiation, the temperature, ratio of damage, and structure of the bacteria were examined. The cavitation effect of the device was detected by the passive cavitation detection method. RESULTS: After US irradiation at the different doses (intensity and exposure time), no significant temperature change was found in all sample suspensions. The ratio of bacterial damage tested by flow cytometry and the optical density of the suspensions as assayed by the 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide colorimetric method showed that the US-irradiated groups were significantly different from the control group. The BCG damage ratio reached 28% at the intensity of 1.53 W/cm(2). Transmission electron microscopic results showed that the bacterial structure of BCG could be destroyed by low frequency, low-intensity US. CONCLUSIONS: Low-frequency, low-intensity US can cause acute injury to BCG, and the degree of injury is closely correlated with the US dose applied. PMID- 26887449 TI - Three-Dimensional Sonography of Axillary Lymph Nodes in Patients With Breast Cancer. AB - Sonography is useful in the evaluation of axillary lymph nodes in patients with breast cancer. In this pictorial essay, we review the range of grayscale and Doppler appearances of abnormal axillary lymph nodes on 2-dimensional and 3 dimensional imaging. PMID- 26887450 TI - Evaluation of Fetal First and Second Cervical Vertebrae: Normal or Abnormal? AB - OBJECTIVES: To use 3-dimensional sonographic volumes to evaluate the variable appearance of the normal fetal cervical spine and craniocervical junction, which if unrecognized may lead to misdiagnosis of malalignment at the first and second cervical vertebrae (C1 and C2). METHODS: Three-dimensional sonographic volumes of the fetal cervical spine were obtained from 24 fetuses at gestational ages between 12 weeks 6 days and 35 weeks 1 day. The volumes were reviewed on 4 dimensional software, and the vertebral level was determined by labeling the first rib-bearing vertebra as the first thoracic vertebra. The ossification centers of the cervical spine and occipital condyles were then labeled accordingly and evaluated for alignment and structure by rotating the volumes in oblique planes. The appearance on multiplanar images was assessed for possible perceived anomalies, including malalignment, particularly at the C1 and C2 levels. Evidence of head rotation was correlated with the presence of possible malalignment at C1-C2. Head rotation was identified in the axial plane by measuring the angle of the anteroposterior axis of C1 to the anteroposterior axis of C2. RESULTS: Of the 24 fetuses, 16 had adequate quality to assess the entire cervical spine and craniocervical junction. All 16 cases showed an osseous component of C1 that did not align directly with C2 on some of the multiplanar images when the volumes were rotated, which could lead to suspected diagnosis of spinal malalignment or a segmental abnormality, as occurred in 2 clinical cases in our practice. All 16 cases showed at least some degree of head rotation, ranging from 2 degrees to 36 degrees , which may possibly explain the apparent malalignment. The lateral offset from C1 to C2 ranged from 0.0 to 3.3 mm. CONCLUSIONS: The normal C1 and C2 ossification centers may appear to be malaligned due to normal offsetting (lateral displacement) of C1 on C2. An understanding of the normal development of the cervical spine is important in assessing spinal anatomy. PMID- 26887451 TI - Erratum to: Results of multicenter double-blind placebo-controlled phase II clinical trial of Panagen preparation to evaluate its leukostimulatory activity and formation of the adaptive immune response in patients with stage II-IV breast cancer. PMID- 26887452 TI - Ethics, Science and Mind Control: J. M. Rodriguez-Delgado's Legacy. AB - This work analyses the evolution of the scientific visibility of the neurophysiologist Jose Manuel Rodriguez Delgado. It examines the longitudinal evolution from 1955 to 2013 of an article (Delgado, Roberts, & Miller, 1954) studying the neurological basis of learning and motivation and compares it with a coetaneous article (Olds & Milner, 1954) with a similar subject and methodology. Both studies have been essential in Psychology. This work analyses the number of times each article has been cited between 1955-1984 and 1985-2013. The results show that the visibility of James Olds and Peter Milner's article (expressed in number of citations between 1955-1984 and 1985-2013) has longitudinally increased (p < .001), whereas the number of citations received by Jose Manuel Rodriguez Delgado et al.'s article has significantly reduced (p < .001). The results are discussed and the low visibility of Delgado's article is explained through historical and social factors, including the growing concern about compliance with bioethical and research guidelines and the controversial media projection of the Spanish scientist, not by the intrinsic value or the scientific repercussion of the compared articles. PMID- 26887453 TI - Back to Earth. PMID- 26887454 TI - Green-sky thinking. PMID- 26887455 TI - Chow down. PMID- 26887456 TI - Put innovation science at the heart of discovery. PMID- 26887468 TI - Gravitational waves: How LIGO forged the path to victory. PMID- 26887469 TI - Young scientists poised to ride the gravitational wave. PMID- 26887470 TI - A mouse's house may ruin experiments. PMID- 26887471 TI - Biologists urged to hug a preprint. PMID- 26887472 TI - New Delhi car ban yields trove of pollution data. PMID- 26887474 TI - Corrections. PMID- 26887473 TI - UN agency proposes greenhouse-gas standard for aircraft. PMID- 26887475 TI - What sparked the Cambrian explosion? PMID- 26887476 TI - The truth about exoplanets. PMID- 26887477 TI - Pollution: Three steps to a green shipping industry. PMID- 26887481 TI - Reproducibility: International accord on open data. PMID- 26887482 TI - Nuclear waste: Weapons plutonium riskier above ground. PMID- 26887483 TI - Energy: Technology alone won't save climate. PMID- 26887484 TI - India: Formalize recycling of electronic waste. PMID- 26887485 TI - Invasive species: Control wildlife pathogens too. PMID- 26887486 TI - Marvin L. Minsky (1927-2016). PMID- 26887487 TI - Quantum physics: Photons paired with phonons. PMID- 26887489 TI - Climate science: Ice streams waned as ice sheets shrank. PMID- 26887490 TI - Cell biology: Form follows function for mitochondria. PMID- 26887491 TI - Developmental biology: Females have a lot of guts. PMID- 26887492 TI - Super-catastrophic disruption of asteroids at small perihelion distances. AB - Most near-Earth objects came from the asteroid belt and drifted via non gravitational thermal forces into resonant escape routes that, in turn, pushed them onto planet-crossing orbits. Models predict that numerous asteroids should be found on orbits that closely approach the Sun, but few have been seen. In addition, even though the near-Earth-object population in general is an even mix of low-albedo (less than ten per cent of incident radiation is reflected) and high-albedo (more than ten per cent of incident radiation is reflected) asteroids, the characterized asteroids near the Sun typically have high albedos. Here we report a quantitative comparison of actual asteroid detections and a near Earth-object model (which accounts for observational selection effects). We conclude that the deficit of low-albedo objects near the Sun arises from the super-catastrophic breakup (that is, almost complete disintegration) of a substantial fraction of asteroids when they achieve perihelion distances of a few tens of solar radii. The distance at which destruction occurs is greater for smaller asteroids, and their temperatures during perihelion passages are too low for evaporation to explain their disappearance. Although both bright and dark (high- and low-albedo) asteroids eventually break up, we find that low-albedo asteroids are more likely to be destroyed farther from the Sun, which explains the apparent excess of high-albedo near-Earth objects and suggests that low albedo asteroids break up more easily as a result of thermal effects. PMID- 26887493 TI - Universal resilience patterns in complex networks. AB - Resilience, a system's ability to adjust its activity to retain its basic functionality when errors, failures and environmental changes occur, is a defining property of many complex systems. Despite widespread consequences for human health, the economy and the environment, events leading to loss of resilience--from cascading failures in technological systems to mass extinctions in ecological networks--are rarely predictable and are often irreversible. These limitations are rooted in a theoretical gap: the current analytical framework of resilience is designed to treat low-dimensional models with a few interacting components, and is unsuitable for multi-dimensional systems consisting of a large number of components that interact through a complex network. Here we bridge this theoretical gap by developing a set of analytical tools with which to identify the natural control and state parameters of a multi-dimensional complex system, helping us derive effective one-dimensional dynamics that accurately predict the system's resilience. The proposed analytical framework allows us systematically to separate the roles of the system's dynamics and topology, collapsing the behaviour of different networks onto a single universal resilience function. The analytical results unveil the network characteristics that can enhance or diminish resilience, offering ways to prevent the collapse of ecological, biological or economic systems, and guiding the design of technological systems resilient to both internal failures and environmental changes. PMID- 26887494 TI - Ice stream activity scaled to ice sheet volume during Laurentide Ice Sheet deglaciation. AB - The contribution of the Greenland and West Antarctic ice sheets to sea level has increased in recent decades, largely owing to the thinning and retreat of outlet glaciers and ice streams. This dynamic loss is a serious concern, with some modelling studies suggesting that the collapse of a major ice sheet could be imminent or potentially underway in West Antarctica, but others predicting a more limited response. A major problem is that observations used to initialize and calibrate models typically span only a few decades, and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves over longer timescales. This represents one of the largest sources of uncertainty when predicting the contributions of ice sheets to sea-level rise. A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing. Here we reconstruct the activity of 117 ice streams that operated at various times during deglaciation of the Laurentide Ice Sheet (from about 22,000 to 7,000 years ago) and show that as they activated and deactivated in different locations, their overall number decreased, they occupied a progressively smaller percentage of the ice sheet perimeter and their total discharge decreased. The underlying geology and topography clearly influenced ice stream activity, but--at the ice-sheet scale--their drainage network adjusted and was linked to changes in ice sheet volume. It is unclear whether these findings can be directly translated to modern ice sheets. However, contrary to the view that sees ice streams as unstable entities that can accelerate ice-sheet deglaciation, we conclude that ice streams exerted progressively less influence on ice sheet mass balance during the retreat of the Laurentide Ice Sheet. PMID- 26887495 TI - The sexual identity of adult intestinal stem cells controls organ size and plasticity. AB - Sex differences in physiology and disease susceptibility are commonly attributed to developmental and/or hormonal factors, but there is increasing realization that cell-intrinsic mechanisms play important and persistent roles. Here we use the Drosophila melanogaster intestine to investigate the nature and importance of cellular sex in an adult somatic organ in vivo. We find that the adult intestinal epithelium is a cellular mosaic of different sex differentiation pathways, and displays extensive sex differences in expression of genes with roles in growth and metabolism. Cell-specific reversals of the sexual identity of adult intestinal stem cells uncovers the key role this identity has in controlling organ size, reproductive plasticity and response to genetically induced tumours. Unlike previous examples of sexually dimorphic somatic stem cell activity, the sex differences in intestinal stem cell behaviour arise from intrinsic mechanisms that control cell cycle duration and involve a new doublesex- and fruitless independent branch of the sex differentiation pathway downstream of transformer. Together, our findings indicate that the plasticity of an adult somatic organ is reversibly controlled by its sexual identity, imparted by a new mechanism that may be active in more tissues than previously recognized. PMID- 26887498 TI - DNA tags help the hunt for drugs. PMID- 26887497 TI - Crystal structure of the Rous sarcoma virus intasome. AB - Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase-DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical three-domain integrase bound to DNA remained elusive. Here we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein-DNA and protein-protein contacts that show both conserved and distinct features compared with those observed for prototype foamy virus integrase. Our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses. PMID- 26887496 TI - Cryo-EM reveals a novel octameric integrase structure for betaretroviral intasome function. AB - Retroviral integrase catalyses the integration of viral DNA into host target DNA, which is an essential step in the life cycle of all retroviruses. Previous structural characterization of integrase-viral DNA complexes, or intasomes, from the spumavirus prototype foamy virus revealed a functional integrase tetramer, and it is generally believed that intasomes derived from other retroviral genera use tetrameric integrase. However, the intasomes of orthoretroviruses, which include all known pathogenic species, have not been characterized structurally. Here, using single-particle cryo-electron microscopy and X-ray crystallography, we determine an unexpected octameric integrase architecture for the intasome of the betaretrovirus mouse mammary tumour virus. The structure is composed of two core integrase dimers, which interact with the viral DNA ends and structurally mimic the integrase tetramer of prototype foamy virus, and two flanking integrase dimers that engage the core structure via their integrase carboxy-terminal domains. Contrary to the belief that tetrameric integrase components are sufficient to catalyse integration, the flanking integrase dimers were necessary for mouse mammary tumour virus integrase activity. The integrase octamer solves a conundrum for betaretroviruses as well as alpharetroviruses by providing critical carboxy-terminal domains to the intasome core that cannot be provided in cis because of evolutionarily restrictive catalytic core domain-carboxy-terminal domain linker regions. The octameric architecture of the intasome of mouse mammary tumour virus provides new insight into the structural basis of retroviral DNA integration. PMID- 26887500 TI - Continuous-wave phase-matched molecular optical modulator. AB - In optical modulation, the highest available modulation rate is basically limited to the GHz frequency range at best. This is because optical modulation is often performed using electro-optic or acousto-optic effects that require application of an external signal to solid-state nonlinear optical materials. Here we describe optical modulation of continuous-wave radiation at frequencies exceeding 10 THz based on ultrafast variation of molecule polarizability arising from coherent molecular motion. The optical modulation efficiency is extensively enhanced by fulfilling phase-matching conditions with the help of dispersion control of the optical cavity, generating sidebands with a highest ratio of 7.3 * 10(-3). These results will pave the way for development of versatile optical modulation-based techniques in a wide range of research fields in optical sciences, such as mode-locked lasers operating in the THz range. PMID- 26887501 TI - FLP-4 neuropeptide and its receptor in a neuronal circuit regulate preference choice through functions of ASH-2 trithorax complex in Caenorhabditis elegans. AB - Preference choice on food is an important response strategy for animals living in the environment. Using assay system of preference choice on bacterial foods, OP50 and PA14, we identified the involvement of ADL sensory neurons in the control of preference choice in Caenorhabditis elegans. Both genetically silencing and ChR2 mediated activation of ADL sensory neurons significantly affected preference choice. ADL regulated preference choice by inhibiting function of G protein coupled receptor (GPCR)/SRH-220. ADL sensory neurons might regulate preference choice through peptidergic signals of FLP-4 and NLP-10, and function of FLP-4 or NLP-10 in regulating preference choice was regulated by SRH-220. FLP-4 released from ADL sensory neurons further regulated preference choice through its receptor of NPR-4 in AIB interneurons. In AIB interneurons, NPR-4 was involved in the control of preference choice by activating the functions of ASH-2 trithorax complex consisting of SET-2, ASH-2, and WDR-5, implying the crucial role of molecular machinery of trimethylation of histone H3K4 in the preference choice control. The identified novel neuronal circuit and the underlying molecular mechanisms will strengthen our understanding neuronal basis of preference choice in animals. PMID- 26887502 TI - Fecal Lipid Excretion after Consumption of a Black Tea Polyphenol Containing Beverage-Randomized, Placebo-Controlled, Double-Blind, Crossover Study. AB - Obesity is a serious medical condition worldwide. Inhibition of lipid absorption is very important in preventing obesity. In a previous study, we found that postprandial elevation of triacylglycerol was suppressed by the intake of black tea polyphenol (BTP). We also reported that BTP caused lipid excretion into feces in an animal study. The present study is a clinical trial that examined lipid excretion. In this randomized, placebo-controlled, double-blind, crossover study, in the first test period participants were asked to drink either a beverage containing 55 mg BTP or a control beverage without BTP 3 times a day for 10 d. After an 11-d interval, for the second test period, they then drank the alternate test beverage 3 times a day for 10 d. During the test periods, the participants were asked to eat meals standardized according to calorie and fat content. Stool samples were obtained during the last 3 d of each test period for fecal lipid measurements. Total lipid excretion increased from 5.51+/-1.73 to 6.87+/-1.91 g/3 d after BTP intake in comparison with intake of the control beverage. These results indicated that BTP increased lipid excretion. PMID- 26887504 TI - Thermodynamics and efficiency of an autonomous on-chip Maxwell's demon. AB - In his famous letter in 1870, Maxwell describes how Joule's law can be violated "only by the intelligent action of a mere guiding agent", later coined as Maxwell's demon by Lord Kelvin. In this letter we study thermodynamics of information using an experimentally feasible Maxwell's demon setup based a single electron transistor capacitively coupled to a single electron box, where both the system and the Demon can be clearly identified. Such an engineered on-chip Demon measures and performes feedback on the system, which can be observed as cooling whose efficiency can be adjusted. We present a detailed analysis of the system and the Demon, including the second law of thermodynamics for bare and coarse grained entropy production and the flow of information as well as efficiency of information production and utilization. Our results demonstrate how information thermodynamics can be used to improve functionality of modern nanoscale devices. PMID- 26887503 TI - Ancestry variation and footprints of natural selection along the genome in Latin American populations. AB - Latin American populations stem from the admixture of Europeans, Africans and Native Americans, which started over 400 years ago and had lasted for several centuries. Extreme deviation over the genome-wide average in ancestry estimations at certain genomic locations could reflect recent natural selection. We evaluated the distribution of ancestry estimations using 678 genome-wide microsatellite markers in 249 individuals from 13 admixed populations across Latin America. We found significant deviations in ancestry estimations including three locations with more than 3.5 times standard deviations from the genome-wide average: an excess of European ancestry at 1p36 and 14q32, and an excess of African ancestry at 6p22. Using simulations, we could show that at least the deviation at 6p22 was unlikely to result from genetic drift alone. By applying different linguistic groups as well as the most likely ancestral Native American populations as the ancestry, we showed that the choice of Native American ancestry could affect the local ancestry estimation. However, the signal at 6p22 consistently appeared in most of the analyses using various ancestral groups. This study provided important insights for recent natural selection in the context of the unique history of the New World and implications for disease mapping. PMID- 26887507 TI - [Targeted therapy for thyroid cancer]. PMID- 26887505 TI - Long Noncoding RNA LOC100129973 Suppresses Apoptosis by Targeting miR-4707-5p and miR-4767 in Vascular Endothelial Cells. AB - Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are key regulators of multiple biological processes by altering gene expression at various levels. Apoptosis in vascular endothelial cells (VECs) is closely linked to numerous cardiovascular diseases, such as arteriosclerosis, thrombus formation and plaque erosion. However, studies on lncRNAs in the cardiovascular system are just beginning. And thus far, no anti-apoptosis lncRNAs have been identified in VECs. Here, we focused on the anti-apoptosis roles of lncRNAs in the serum and FGF-2 starvation-induced apoptosis of VECs. Using microarray analysis, we found a novel lncRNA LOC100129973 which acted as an apoptosis inhibitor in VECs. Through sponging miR-4707-5p and miR-4767, lncRNA LOC100129973 upregulated the expression of two apoptosis repressors gene, Apoptosis Inhibitor 5 (API5) and BCL2 like 12 (BCL2L12), and thus alleviated the serum and FGF-2 starvation-induced apoptosis in VECs. This evidence suggests that lncRNA LOC100129973 is an attractive target to improve endothelial function and for therapy of apoptosis related cardiovascular diseases. PMID- 26887506 TI - A Modular Assembly Platform for Rapid Generation of DNA Constructs. AB - Traditional cloning methods have limitations on the number of DNA fragments that can be simultaneously manipulated, which dramatically slows the pace of molecular assembly. Here we describe GMAP, a Gibson assembly-based modular assembly platform consisting of a collection of promoters and genes, which allows for one step production of DNA constructs. GMAP facilitates rapid assembly of expression and viral constructs using modular genetic components, as well as increasingly complicated genetic tools using contextually relevant genomic elements. Our data demonstrate the applicability of GMAP toward the validation of synthetic promoters, identification of potent RNAi constructs, establishment of inducible lentiviral systems, tumor initiation in genetically engineered mouse models, and gene-targeting for the generation of knock-in mice. GMAP represents a recombinant DNA technology designed for widespread circulation and easy adaptation for other uses, such as synthetic biology, genetic screens, and CRISPR-Cas9. PMID- 26887508 TI - [Transforming growth factor-beta1 induces bone marrow-derived mesenchymal stem cells to differentiate into cancer-associated fibroblasts]. AB - OBJECTIVE: To investigate the effect of transforming growth factor-beta1 (TGF beta1) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into cancer-associated fibroblasts(CAFs). METHODS: MSCs were cultured in alpha-MEM with recombinant human TGF-beta1 or in tumor-conditioned medium.The expression of CAFs markers were detected by immunofluorescence and quantitative RT-PCR. RESULTS: The qRT-PCR assay showed that the expression of CAFs markers FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin were 9.92+/-2.16, 7.76+/ 1.28, 3.04+/-0.95, 3.28+/-2.16, 2.13+/-0.71, 1.41+/-0.66, 2.25+/-0.86 and 1.38+/ 0.56, respectively, significantly upregulated in the MSCs co-cultured with TGF beta1 or TCM. The relative levels of FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin mRNA in the TCM group were 7.52+/-1.76, 5.02+/-1.18, 1.98+/-1.19, 1.82+/ 1.19, 2.95+/-0.86, 1.44+/-0.67, 2.08+/-0.74 and 1.47+/-0.55, respectively, indicating that MSCs can express CAFs phenotype.TGF beta signaling pathway inhibitor SB-431542 could inhibit the differentiation. Both immunofluorescence and Western blot confirmed the above results. CONCLUSIONS: TGF-beta1 induces differentiation of local MSCs to CAFs by upregulating the expression of pSmad3, so as to further promote the growth of cancer cells. PMID- 26887509 TI - [Effect of colon cancer cell-derived IL-1alpha on the migration and proliferation of vascular endothelial cells]. AB - OBJECTIVE: To explore the effect of colon cancer cell-derived interleukin-1alpha on the migration and proliferation of human umbilical vein endothelial cells as well as the role of IL-1alpha and IL-1ra in the angiogenesis process. METHODS: Western blot was used to detect the expression of IL-1alpha and IL-1R1 protein in the colon cancer cell lines with different liver metastatic potential. We also examined how IL-1alpha and IL-1ra influence the proliferation and migration of umbilical vascular endothelial cells assessed by PreMix WST-1 assay and migration assay, respectively. Double layer culture technique was used to detect the effect of IL-1alpha on the proliferation and migration of vascular endothelial cells and the effect of IL-1ra on the vascular endothelial cells. RESULTS: Western blot analysis showed that IL-1alpha protein was only detected in highly metastatic colon cancer HT-29 and WiDr cells, but not in the lowly metastatic CaCo-2 and CoLo320 cells.Migration assay showed that there were significant differences in the number of penetrated cells between the control (17.9+/-3.6) and 1 ng/ml rIL 1alpha group (23.2+/-4.2), 10 ng/ml rIL-1alpha group (31.7+/-4.5), and 100 ng/ml rIL-1alpha group (38.6+/-4.9), showing that it was positively correlated with the increasing concentration of rIL-1alpha (P<0.01 for all). The proliferation assay showed that the absorbance values were 1.37+/-0.18 in the control group, and 1.79+/-0.14 in the 1 ng/ml rIL-1alpha group, 2.14+/-0.17 in the 10 ng/ml rIL 1alpha group, and 2.21+/-0.23 in the 100 ng/ml rIL-1alpha group, showing a positive correlation with the increasing concentration of rIL-1alpha(P<0.01 for all). IL-1ra significantly inhibited the proliferation and migration of vascular endothelial cells (P<0.01). The levels of VEGF protein were (1.697+/-0.072) ng/ml, (3.507+/-0.064)ng/ml and (4.139+/-0.039)ng/ml in the control, HUVECs+ IL 1alpha and HUVECs+ HT-29 co-culture system groups, respectively, showing a significant difference between the control and HUVECs+ 10 pg/ml rIL-1alpha groups and between the control and HUVECs+ HT-29 groups (P<0.01 for both). CONCLUSIONS: Our findings indicate that colon cancer cell-derived IL-1alpha plays an important role in the liver metastasis of colon cancer through increased VEGF level of the colon cancer cells and enhanced vascular endothelial cells proliferation, migration and angiogenesis, while IL-1ra can suppress the effect of IL-1alpha and inhibit the angiogenesis in colon cancer. PMID- 26887510 TI - [Detection and significance of BRAF gene in mature T/NK cell lymphoma]. AB - OBJECTIVE: we aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma. METHODS: Firstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes. RESULTS: We did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207+/-0.013, 8.412+/ 0.615 and 36.720+/-1.797, respectively, and protein expressions were 0.051+/ 0.003, 0.102+/-0.013, 0.113+/-0.017 and 0.304+/-0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05). CONCLUSION: The expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma. PMID- 26887511 TI - [Clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation]. AB - OBJECTIVE: To study the clinicopathological features and prognosis of renal cell carcinoma with sarcomatoid differentiation (RCCS). METHODS: The clinical data and pathological materials of 18 RCCS cases were retrospectively reviewed.The follow up data were available in 13 RCCS cases, and were compared with the follow up data of 20 cases of clear cell renal cell carcinoma (RCC). RESULTS: The 18 RCCS patients included 14 males and 4 females, and were 49-79 years old (mean age: 62 years old). On gross examination, the tumor size was 3-19 cm in diameter (mean diameter: 9.8 cm). Histologically, all tumors were composed of a mixture of typical RCC with sarcomatoid component, including 9 clear cell RCC, 3 chromophobe RCC and one papillary RCC. The sarcomatoid components included 9 cases of fibrosarcoma, 3 cases of leiomyosarcoma, 5 cases of malignant fibrous histocytoma and one case of undifferentiated sarcoma. Immunohistochemistry showed that the sarcomatoid components were strongly vimentin-positive in 18 cases, and one or more epithelial markers (EMA, AE1/AE3, CK7, CK18) were expressed to varying degrees in 14 cases, but the high-molecular weight keratin 34betaE12 was scarcely expressed. The sarcomatoid components presented positive expressions of CAIX in 88.9% (16/18) and CD10 in 72.2% (13/18) cases. Among the 18 RCCS patients, 13 patients were followed-up: 9 patients died in 1-25 months after the surgery, of which 5 cases died of lung or bone metastasis, and 4 patients died of systemic failure. The twenty RCC cases without sarcomatoid differentiation were followed up for 3-65 months after the surgery, and the majority of them was alive uneventfully except for 2 cases who died of lung or bone metastasis of the tumor. The Kaplan-Meier survival analysis showed that the median survival time of the 18 RCCS patients was 8 months, while that of the 20 RCC cases without sarcomatoid differentiation was 62 months (P<0.001). CONCLUSIONS: The presence of sarcomatoid differentiation in renal cell carcinoma indicates highly aggressive behavior and poor prognosis. The positive expressions of the immune markers CAIX and CD10 may play important roles in the transformation from renal cell carcinoma to sarcomatoid component. PMID- 26887512 TI - [Expression and clinical significance of MTDH and VEGF in triple-negative breast cancer]. AB - OBJECTIVE: To study the expression and clinical significance of MTDH and VEGF in triple-negative breast cancer (TNBC). METHODS: Tissue samples of 168 breast cancers (including 112 TNBC tissue and 56 non-TNBC tissue), 10 breast fibroadenomas and 15 normal breast tissues were collected. Postoperative specimens were examined by immunohistochemistry for MTDH and VEGF expression. The correlation between the expression of MTDH and VEGF and clinicopathological features was analyzed. RESULTS: MTDH and VEGF were expressed in 57.1% and 49.4% of breast cancer patients, 64.3% and 56.3% in TNBC patients, respectively, significantly higher than that in the non-TNBC tissues, breast fibroadenomas and normal breast tissues (P<0.05 for all). Statistically significant correlation was found between the MTDH and VEGF expressions (r=0.356, P<0.001). Moreover, MTDH expression was correlated with tumor size, BMI index, lymph node metastasis, pathological stage, recurrence and metastasis, and the expression of p53 and Ki 67 proteins (P<0.05 for all). The VEGF protein expression was correlated with lymph node metastasis, pathological staging, recurrence and metastasis, and the expression of Ki-67 protein (P<0.05 for all). The patients with high expression of MTDH and VEGF showed a lower DFS and OS (P<0.05 for both). CONCLUSIONS: MTDH and VEGF expression may be correlated with tumor angiogenesis and progression and has the potential to be valuable prognostic factors in patients with TNBC. PMID- 26887513 TI - [Association between the expression of IGF1R and estrogen receptor and efficacy of neoadjuvant chemotherapy in beast cancer patients]. AB - OBJECTIVE: To detect the expression of IGF1R and estrogen receptor, and to explore the relationship between their expression and the pathological complete response (pCR) rate of neoadjuvant chemotherapy (docetaxel plus epirubicin) in breast cancer patients. METHODS: We selected 139 women with breast cancer who underwent neoadjuvant chemotherapy (docetaxel plus epirubicin), and detected the expression of IGF1R and estrogen receptor in the samples taken before chemotherapy by Immunohistochemistry. The association between their expression and pCR rate of neoadjuvant chemotherapy was analyzed. RESULTS: Among the 139 cases, IGF1R was highly expressed in 45.3% (63/139) cases, and ER was positively expressed in 62.6% (87/139) cases. IGF1R was highly expressed in 54.0% (47/87) of the ER+ cases, significantly higher than that of ER- cases (30.8%, P<0.01). The overall pCR rate of all the 139 patients who received docetaxel plus epirubicin as neoadjuvant chemotherapy was 10.1% (14/139). The pCR rate was 19.2% (10/52) of the ER- patients and 4.6% (4/87) of the ER+ patients (P<0.05). The pCR rate was 10.5% (8/76) in the patients with low IGF1R expression and 9.5% (6/63) in the patients with high IGF1R expression (P>0.05). The patients with negative expression of ER and high expression of IGF1R showed the highest pCR rate (31.2%, P<0.01). CONCLUSIONS: Breast cancer patients with negative expression of ER and high expression of IGF1R are more sensitive to neoadjuvant chemotherapy of docetaxel plus epirubicin, and their pCR rate is significantly higher than that of other patients. PMID- 26887514 TI - [Effect of perioperative blood transfusion on the prognosis of gastric cancer]. AB - OBJECTIVE: To explore the association of perioperative blood transfusion (PBT) with survival of gastric cancer after surgery. METHODS: We retrospectively reviewed the medical records of 1 000 gastric cancer patients, including 738 non transfused (73.8%) and 262 transfused (26.2%) cases. A one to one match was created using propensity score analysis, except preoperative hemoglobin level and operative blood loss. The survival was analyzed by Kaplan-Meier survival model. RESULTS: The 5-year survival rate of the 1 000 cases of gastric cancer patients was 39.9%. Before matching, there was a significant difference between transfused group (33.6%) and non-transfused group (49.1%, P<0.005). Univariate analysis showed that age, tumor size, hemoglobin level, albumin level, depth of invasion, lymph node metastasis, lymph node dissection, surgery mode, adjuvant chemotherapy, blood loss and blood transfusion during perioperative period were associated with prognosis in the gastric cancer patients (all P<0.05). Multivariate analysis showed that tumor invasion, lymph node metastasis, lymph node dissection, chemotherapy and perioperative blood transfusion were independent prognostic factors in gastric cancer (all P<0.05). After matching, the 5-year survival rate of the 262 non-transfused patients was 37.7%, while that of the 262 transfused patients was 33.6% (P>0.05). CONCLUSIONS: Perioperative blood transfusion has no significant effect on the prognosis of gastric cancer patients. PMID- 26887515 TI - [Patterns of lymphatic spread in thoracic esophageal squamous cell carcinoma: a study of 313 cases]. AB - OBJECTIVE: We analyzed the lymph node (MLNs) metastasis of thoracic esophageal squamous cell carcinoma (ESCC) to explore the patterns of lymphatic spread and the rational surgical procedure and extent of lymph node dissection for ESCC. METHODS: We retrospectively evaluated 313 consecutive patients treated in our hospital between January 2010 and May 2014 who underwent minimally invasive esophagectomy (MIE) for ESCC. The information of lymph node status was obtained and the features of lymph node metastasis were analyzed. RESULTS: Of the 313 cases, 122 (39.0%) were found to have lymph node metastasis. In the 4461 dissected lymph nodes, metastasis was identified in 294 (6.6%) lymph nodes. The recurrent laryngeal nerve lymph nodes were the most frequent metastatic nodes with a metastasis rate of 25.2%, followed by the paracardiac and left gastric artery lymph nodes (18.2%). Chi-square test showed that the lymph node metastasis is associated with tumor invasion and tumor differentiation (P<0.001 for both). Metastases were more frequently found in the recurrent laryngeal nerve lymph nodes in patients with tumors in the upper third esophagus and with histologically poor differentiation (P<0.05 for both). The metastasis rate of para-cardiac and left gastric artery lymph nodes was associated with tumor in the lower third of esophagus, T stage and differentiation (all P<0.05). Logistic regression analysis showed that tumor differentiation and location are independent factors affecting the metastasis of recurrent laryngeal nerve lymph nodes (P<0.05 for all). T stage, tumor differentiation and location were independent factors associated with metastasis of para-cardiac and left gastric artery lymph nodes (P<0.05 for all). CONCLUSIONS: (1) Metastases of thoracic esophageal carcinoma are often found in the recurrent laryngeal nerve lymph nodes, para-cardiac and left gastric artery lymph nodes. (2) Extensive lymph node dissection should be performed for ESCC with poor differentiation and deep tumor invasion. PMID- 26887516 TI - [CT differential diagnosis of cystic nephroma and multilocular cystic renal cell carcinoma]. AB - OBJECTIVE: To study the CT findings of cystic nephroma (CN) and multilocular cystic renal cell carcinoma (MCRCC) and to improve the accuracy of preoperative diagnosis of these two diseases. METHODS: The CT findings of nine CN cases and 19 MCRCC cases confirmed by pathology were blindly reviewed and compared with their pathological results. Fisher's exact test and independent-samples T test were applied to statistically analyze some of the CT features of the CN and MCRCC lesions. RESULTS: The thickness of cystic walls and partitions in the nine CN cases ranged from 0.5 to 5 mm. Cystic walls and partitions were slightly thicker in some parts without visible mural nodules. Varying amounts of solid tissue could be found in all the 19 MCRCC tumors, and the cystic walls and partitions were found partially thickened ranging from 3 mm to 13 mm. Eight cases were with mural nodules (nodule diameter: 4.5-16 mm). Nine cases of CN tumors were lobulated and 7 protruded into the renal sinus. Three out of the 19 MCRCC presented shallow lobulation, and 7 tumors protruded into the renal sinus. The CT contrast-enhancement scanning displayed moderate delayed enhancement in the cystic walls and partitions in 8 cases. The enhanced scanning revealed that all the nine cases showed enhancement of the cystic walls and partitions, while 8 cases of them had mild to moderate delayed enhancement. The cystic walls, partitions and nodules were enhanced in 19 MRCC cases, among them 17 cases displayed obvious enhancement in the cortical phase. Among the differences of CT findings between MC and MRCC, the shallow lobulation, protruding into the renal sinus, mural nodules, cystic wall and partition thickness, and net growth in the cortical and nephrographic phase were statistically significantly different (P<0.05 for all). CONCLUSIONS: CT scan can provide significant evidence for CN and MCRCC diagnosis. CN cases usually present relatively thin and even cystic walls and partitions without mural nodules and with shallow lobulation and protruding into the renal sinus. The enhancement is mild to moderate, dynamic and delayed, while the opposite CT findings may indicate a higher possibility of MCRCC. PMID- 26887517 TI - [Role of multiphasic multidetector CT imaging in differential diagnosis of small renal cell carcinoma]. AB - OBJECTIVE: To explore the possibility of predicting the histopathological types of small renal cell carcinoma (RCC) by analyzing the different ways of enhancement with multiphasic multidetector computed tomography (MDCT) of small renal cell carcinomas (diameter<=4 cm). METHODS: CT images of 93 cases, diagnosed as RCC by pathology, were analyzed retrospectively, including 70 clear cell renal cell carcinoma (CCRCC), 13 papillary renal cell carcinoma (PRCC) and 10 chromophobe renal cell carcinoma (CRCC). All of the cases were examined by multiphasic multidetector CT scanning. RESULTS: In plain scans, 46 CCRCCs were homogeneous, 21 CCRCCs were heterogeneous with low-density area and 3 of them had calcification. CCRCCs were enhanced in contrast scan with a presence of "wash in and wash out" enhancement in general. 11 PRCCs were homogeneous and 2 PRCCs had calcification. Slight-homogeneous enhancement and "delayed enhancement" were present in the PRCCs. Six CRCCs were homogeneous and 2 were calcified, 2 CRCCs were heterogeneous with low-density area. The CRCCs presented as slight or moderate enhancement and 5 CRCCs as homogeneous enhancement, while one CRCC was "spoke-wheel-like enhancement", with a trend of "delayed enhancement". Statistically significant differences were revealed among the actual enhanced CT values, the ratio of enhanced CT value to aorta CT value in the corticomedullary phase, nephrographic phase and excretory phase between the CCRCCs and non-CCRCCs (P<0.001). The analysis of receiver operating characteristic curves (ROC) revealed that when the actual enhanced CT value of tumors in CMP larger than 84.2 HU, the ratio of actual enhanced CT value to aorta CT value at the same phase in CMP larger than 0.315 were used as criteria to diagnose CCRCCs and excluded non CCRCCs, the diagnostic value was best. CONCLUSIONS: MDCT is of an important significance in the diagnosis and differential diagnosis of small CCRCCs and non CCRCCs. PMID- 26887518 TI - [Management of vascular crisis of free flaps after reconstruction of head and neck defects caused by tumor resection]. AB - OBJECTIVE: To discuss the management of vascular crisis of free flaps after reconstruction of head and neck defects caused by tumor resection. METHODS: A total of 259 cases of free flap reconstruction performed in the Cancer Hospital of Chinese Academy of Medical Sciences from 2010 to 2013 were retrospectively analyzed, including 89 cases of anterolateral thigh flaps, 48 cases of radial forearm flaps, 46 free fibula flaps, 5 cases of inferior epigastric artery perforator flaps, 5 cases of free latissimus dorsi flaps, one case of lateral arm flap, and one case of medial femoral flap. The surveillance frequency of free flaps was q1h on post-operative day (POD) 1, q2h on POD 2 and 3, and q4h after POD 3. Vascular crises were reviewed for analysis. RESULTS: The incidence rate of vascular crisis was 8.1% (21/259), with 15 males and 6 females. The average age was 54.8 years old (17-68), and the average time of vascular crisis was 100.8 h post-operation (3-432). There were 7 cases of free jejunum flaps and 14 dermal free flaps. Seven of these 21 cases with vascular crisis were rescued by surgery. The success rate of salvage surgery within 72 hours from the primary operation was 54.5% (6/11), significantly higher than that of salvage surgery performed later than 72 hours from primary operation (10.0%, 1/10, P=0.043). There were 14 cases of flap necrosis, two of which died of local infection. CONCLUSION: Early detection of vascular crisis can effectively improve the success rate of salvage, so as to avoid the serious consequences caused by free flap necrosis. PMID- 26887519 TI - [Efficacy and safety of topical PUVA treatment for refractory lesions of mycosis fungoides]. AB - OBJECTIVE: To evaluate the efficacy and safety of topical PUVA treatment of refractory lesions of mycosis fungoides. METHODS: From January 2008 to 2014, a total of 10 patients (4 males and 6 females) with mycosis fungoides were treated with topical PUVA in Peking Union Medical College Hospital, including 7 cases in plaque stage and 3 cases in tumor stage. The average number of lesions were 1.9+/ 0.9. The median age of these patients was (46.0+/-9.4) years. The average course of disease was (12.4+/-7.7) years. Psoralen was applied topically on treatment area 30 min before total body UVA irradiation treatment, 3 times a week. And the efficiency and safety of the therapy were evaluated. RESULTS: All the patients were treated with topical PUVA with a median total dose of (161.60+/-135.96) J/cm2 in an average of (18.10+/-14.61) fractions. Total dose of UVA was (1 953.25+/-829.73) J/cm2, and total number of treatment was (261.90+/-116.79) fractions. The total treatment time was (45.80+/-26.64) months. Complete clinical response (CR) rate was 60.0%, partial response (PR) rate was 30.0%, and the overall response rate (CR+PR) was 90.0%. One patient showed no response. No severe acute or chronic side effects were observed. CONCLUSION: Topical PUVA therapy is effective in the treatment of refractory lesions of mycosis fungoides with little severe side effects. PMID- 26887520 TI - [Outcome of concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer patients]. AB - OBJECTIVE: To analyze the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). METHODS: Clinical data of 251 patients with stage III (76 IIIA and 175 IIIB) NSCLC who received CCRT as initial treatment between Jan 2001 and Dec 2010 in our hospital were reviewed. A median total radiotherapy dose of 60 Gy (range, 50-74 Gy) were delivered. 174 patients were treated with IMRT, 51 with 3D-CRT and 26 with 2D-radiotherapy. EP chemotherapy regimen was administered in 112 patients, PC regimen in 99 patients, topotecan regimen in 18 patients and other regimens in the remaining 22 patients. The efficacy and toxicity of CCRT were retrospectively analyzed. RESULTS: 244 patients were assessable for response, including 6 (2.5%) patients with CR, 183 (75.0%) with PR, 42 (17.2%) with SD and 13 (5.3%) with PD. At a median follow-up period of 20 months, the 1-, 3-, 5- year OS were 69.2%, 31.2%, 23.2%, respectively, and the median OS was 21 months. The 1-, 3-, 5- year PFS were 40.9%, 22.1%, 17.7%, respectively, and the median PFS was 10 months. Patients with stage IIIA NSCLC achieved better 5-year OS than that with IIIB NSCLC (29.2% vs. 20.7%, chi2=2.254, P=0.133). Failure pattern was assessable in 244 patients, including 61 (25.0%) locoregional progression alone, 55 (22.5%) distant metastasis alone and 77 (31.6%) with both. The rates of grade>=3 radiation pneumonitis, esophagitis and hematologic toxicity were 4.4%, 11.2% and 26.4%, respectively. CONCLUSIONS: CCRT provide stage III NSCLC patients favorable outcome with acceptable toxicity. CCRT is standard therapeutic approach for patients with unresectable locally advanced NSCLC. PMID- 26887521 TI - [Clinical efficacy of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy]. AB - OBJECTIVE: To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy. METHODS: Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 ug folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 ug vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 ug folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 ug vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy. RESULTS: The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05). CONCLUSIONS: Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment. PMID- 26887522 TI - [Clinical features and treatment analysis of mantle cell lymphoma]. PMID- 26887523 TI - [Value of 4-quadrant biopsies under colposcopy for detecting precancerous lesions in cervical cancer screening]. AB - OBJECTIVE: To evaluate the value of colposcopical 4-quadrant biopsies for detecting precancerous lesion in cervical cancer screening. METHODS: We used the data of a cross-sectional screening study in 1999, in which 1,997 women received cervical cancer screening in Xiang Yuan County, Shanxi province. The sensitivity, specificity and accuracy of both 4-quadrant biopsy and colposcopy directed biopsy to detect high-grade or more severe squamous intraepithelial lesions (HSIL+) were calculated. RESULTS: 1,784(89.3%) women who received 4-quadrant biopsies and endocervical curettage were negative. 127(6.4%) women were diagnosed as LSIL, 74(3.7%) women as HSIL and 12(0.6%) cases of squamous cell carcinoma. 1,478(74.0%) women who received biopsies in the sites of abnormal lesions were negative, 463(23.2%) cases of LSIL, 41(2.1%) cases of HSIL, 15(0.8%) cases of squamous cell carcinoma. The positive rate was 26.0%(519/1,997) for colposcopy, and the coincidence rate was 73.7% with pathological diagnosis. Sensitivity and specificity were 81.4% and 76.5% of colposcopy for HSIL+. In total of 519 women were found to be with any abnormal colposcopic appearance. The consistency rate between 4-quadrant biopsies and suspicious lesion-directed biopsies was 96.3%. By suspicious lesion-directed biopsy alone, 14.8% cervical lesions were miss diagnosed, of which 8.6%(5/58) cases of total HSIL and 24.1%(14/58) cases of all LSIL. CONCLUSIONS: 4-quadrant biopsy can detect more HSIL+ lesions and is more accurate than suspicious lesion biopsy alone. As an important triage technique to detect cervical precancerous lesions, it can improve the detection rate of HSIL+ lesions in cervical cancer screening. PMID- 26887524 TI - Overstatement in happiness reporting with ordinal, bounded scale. AB - There are various methods by which people can express subjective evaluations quantitatively. For example, happiness can be measured on a scale from 1 to 10, and has been suggested as a measure of economic policy. However, there is resistance to these types of measurement from economists, who often regard welfare to be a cardinal, unbounded quantity. It is unclear whether there are differences between subjective evaluation reported on ordinal, bounded scales and on cardinal, unbounded scales. To answer this question, we developed functional magnetic resonance imaging experimental tasks for reporting happiness from monetary gain and the perception of visual stimulus. Subjects tended to report higher values when they used ordinal scales instead of cardinal scales. There were differences in neural activation between ordinal and cardinal reporting scales. The posterior parietal area showed greater activation when subjects used an ordinal scale instead of a cardinal scale. Importantly, the striatum exhibited greater activation when asked to report happiness on an ordinal scale than when asked to report on a cardinal scale. The finding that ordinal (bounded) scales are associated with higher reported happiness and greater activation in the reward system shows that overstatement bias in happiness data must be considered. PMID- 26887525 TI - R6G molecule induced modulation of the optical properties of reduced graphene oxide nanosheets for use in ultrasensitive SPR sensing. AB - A proper understanding of the role that molecular doping plays is essential to research on the modulation of the optical and electronic properties of graphene. The adsorption of R6G molecules onto defect-rich reduced graphene oxide nanosheets results in a shift of the Fermi energy and, consequently, a variation in the optical constants. This optical variation in the graphene nanosheets is used to develop an ultrasensitive surface plasmon resonance biosensor with a detection limit of 10(-17) M (0.01 fM) at the molecular level. A density functional theory calculation shows that covalent bonds were formed between the R6G molecules and the defect sites on the graphene nanosheets. Our study reveals the important role that defects play in tailoring the properties and sensor device applications of graphene materials. PMID- 26887526 TI - A risk score to identify HIV-infected women most likely to become lost to follow up in the postpartum period. AB - Access to lifelong combination antiretroviral therapy (cART) is expanding among HIV-infected pregnant and breastfeeding women throughout sub-Saharan Africa (SSA). For this strategy to meaningfully improve maternal HIV outcomes, retention in HIV care is essential. We developed a risk score to identify women with high likelihood of loss to follow-up (LTFU) at 6 months postpartum from HIV care, using data from public health facilities in Lusaka, Zambia. LTFU was defined as not presenting for HIV care within 60 days of the last scheduled appointment. We used logistic regression to assess demographic, obstetric and HIV predictors of LTFU and to develop a simple risk score. Sensitivity and specificity were assessed at each risk score cut-point. Among 2029 pregnant women initiating cART between 2009 and 2011, 507 (25%) were LTFU by 6 months postpartum. Parity, education, employment status, WHO clinical stage, duration of cART during pregnancy and number of antenatal care visits were associated with LTFU (p-value < .10). A risk score cut-point of 11 (42nd percentile) had 85% sensitivity (95% CI 82%, 88%) and 22% specificity (95% CI 20%, 24%) to detect women LTFU and would exclude 20% of women from a retention intervention. A risk score cut-point of 18 (69th percentile) identified the 23% of women with the highest probability of LTFU and had sensitivity 32% (95% CI 28%, 36%) and specificity 80% (95% CI 78%, 82%). A risk score approach may be useful to triage a subset of women most likely to be LTFU for targeted retention interventions. PMID- 26887527 TI - Layer-switching cost and optimality in information spreading on multiplex networks. AB - We study a model of information spreading on multiplex networks, in which agents interact through multiple interaction channels (layers), say online vs. offline communication layers, subject to layer-switching cost for transmissions across different interaction layers. The model is characterized by the layer-wise path dependent transmissibility over a contact, that is dynamically determined dependently on both incoming and outgoing transmission layers. We formulate an analytical framework to deal with such path-dependent transmissibility and demonstrate the nontrivial interplay between the multiplexity and spreading dynamics, including optimality. It is shown that the epidemic threshold and prevalence respond to the layer-switching cost non-monotonically and that the optimal conditions can change in abrupt non-analytic ways, depending also on the densities of network layers and the type of seed infections. Our results elucidate the essential role of multiplexity that its explicit consideration should be crucial for realistic modeling and prediction of spreading phenomena on multiplex social networks in an era of ever-diversifying social interaction layers. PMID- 26887528 TI - Preliminary Results From the C-Pulse OPTIONS HF European Multicenter Post-Market Study. AB - BACKGROUND The C-Pulse System is an extra-aortic balloon counterpulsation device. It is used to treat patients with heart failure disease in NYHA functional class III or ambulatory class IV. MATERIAL AND METHODS We present preliminary site reported 6-month data from 3 centers in Germany as part of the prospective observational post-market OPTIONS HF study. RESULTS Between May 2013 and March 2014, the C-Pulse System was implanted in 8 patients (7 male) with a mean age of 61.6+/-9.3 years. Four had ischemic and 4 had non-ischemic cardiomyopathy. No stroke, myocardial infarction, major bleeding, or major infection due to the device were reported. One patient developed non-device-related refractory tachycardia with worsening heart failure 12 h after surgery and underwent left ventricular assist device implantation. Within 6 months of observation, functional status improved from NYHA III to II in 5 patients, and 2 remained in NYHA III. Mean left ventricular ejection fraction increased from 24.3+/-7.9% to 44.5+/-4.5% (p<0.0001). Mean Kansas City Cardiomyopathy Questionnaire overall score improved from 28.6+/-19.1 to 59.1+/-22.5 (p=0.0183). Six-minute walk test was performed in 6 out of 7 patients at follow-up. The mean distance improved from 252.0+/-85.1 m to 279.2+/-87.5 m (p>0.05). One patient was weaned off the device after 6 months of support. CONCLUSIONS The C-Pulse System provides a therapeutic option for patients with moderate-to-severe heart failure and seems to improve quality of life and cardiac function over time. PMID- 26887529 TI - In vitro efficacy of essential oils and extracts of Schinus molle L. against Ctenocephalides felis felis. AB - Extracts and essential oils from plants are important natural sources of pesticides. These compounds are considered an alternative to control ectoparasites of veterinary importance. Schinus molle, an endemic species of Brazil, produces a high level of essential oil and several other compounds. The aim of this work was to determinate the chemical composition of extracts and essential oils of S. molle and further to evaluate the activity against eggs and adults of Ctenocephalides felis felis, a predominant flea that infests dogs and cats in Brazil. In an in vitro assay, the non-polar (n-hexane) extract showed 100% efficacy (800 ug cm(-2); LD50 = 524.80 ug cm(-2)) at 24 and 48 h. Its major compound was lupenone (50.25%). Essential oils from fruits and leaves were evaluated, and had 100% efficacy against adult fleas at 800 ug cm(-2) (LD50 = 353.95 ug cm(-2)) and at 50 ug cm(-2) (LD50 = 12.02 ug cm(-2)), respectively. On the other hand, the essential oil from fruits and leaves was not active against flea eggs. This is the first study that reports the insecticidal effects of essential oils and extracts obtained from Schinus molle against Ctenocephalides felis felis. PMID- 26887530 TI - Conserved miR-26b enhances ovarian granulosa cell apoptosis through HAS2-HA-CD44 Caspase-3 pathway by targeting HAS2. AB - The hyaluronan synthase 2 (HAS2)-hyaluronic acid (HA)-CD44-Caspase-3 pathway is involved in ovarian granulosa cell (GC) functions in mammals. HAS2 is a key enzyme required for HA synthesis and is the key factor in this pathway. However, the regulation of HAS2 and the HAS2-mediated pathway by microRNAs in GCs is poorly understood. Here, we report that miR-26b regulates porcine GC (pGC) apoptosis through the HAS2-HA-CD44-Caspase-3 pathway by binding directly to the 3'- untranslated region of HAS2 mRNA. Knockdown of miR-26b reduced pGC apoptosis. Luciferase reporter assays demonstrated that HAS2 is a direct target of miR-26b in pGCs. Knockdown and overexpression of miR-26b increased and decreased, respectively, HA content, and HAS2 and CD44 expression in pGCs. At the same time, inhibition and overexpression of miR-26b decreased and increased the expression of Caspase-3, a downstream factor in the HAS2-HA-CD44 pathway. Moreover, knockdown of HAS2 enhanced pGC apoptosis, reduced the inhibitory effects of a miR 26b inhibitor on pGC apoptosis, repressed HA content and CD44 expression, and promoted Caspase-3 expression. In addition, overexpression of HAS2 has a opposite effect. Collectively, miR-26b positively regulates pGC apoptosis via a novel HAS2 HA-CD44-Caspase-3 pathway by targeting the HAS2 gene. PMID- 26887532 TI - A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies. AB - Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887531 TI - Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) promotes lung fibroblast proliferation, survival and differentiation to myofibroblasts. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressively fatal disease. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) is a glycosylated transmembrane protein that induces the expression of some matrix metalloproteinase (MMP) in neighboring stromal cells through direct epithelial stromal interactions. EMMPRIN is highly expressed in type II alveolar epithelial cells at the edges of the fibrotic areas in IPF lung sections. However, the exact role of EMMPRIN in IPF is unknown. METHODS: To determine if EMMPRIN contributes to lung fibroblast proliferation, resistance to apoptosis, and differentiation to myofibroblasts, normal Human lung fibroblasts (NHLF) transiently transfected with either EMMPRIN/GFP or GFP were treated with TGF- beta1 from 0 to 10 ng/ml for 48 h and examined for cell proliferation (thymidine incorporation), apoptosis (FACS analysis and Cell Death Detection ELISA assay), cell migration (Modified Boyden chamber) and differentiation to myofibroblasts using Western blot for alpha smooth actin of cell lysates. The effect of EMMPRIN inhibition on NHLF proliferation, apoptosis, migration and differentiation to myofibroblasts after TGF- beta1 treatment was examined using EMMPRIN blocking antibody. We examined the mechanism by which EMMPRIN induces its effects on fibroblasts by studying the beta-catenin/canonical Wnt signaling pathway using Wnt luciferase reporter assays and Western blot for total and phosphorylated beta-catenin. RESULTS: Human lung fibroblasts overexpressing EMMPRIN had a significant increase in cell proliferation and migration compared to control fibroblasts. Furthermore, EMMPRIN promoted lung fibroblasts resistance to apoptosis. Lung fibroblasts overexpressing EMMPRIN showed a significantly increased expression of alpha- smooth muscle actin, a marker of differentiation to myofibroblasts compared to control cells. TGF-beta1 increased the expression of EMMPRIN in lung fibroblasts in a dose-dependent manner. Attenuation of EMMPRIN expression with the use of an EMMPRIN blocking antibody markedly inhibited TGF-beta1 induced proliferation, migration, and differentiation of fibroblasts to myofibroblasts. EMMPRIN overexpression in lung fibroblasts was found to induce an increase in TOPFLASH luciferase reporter activity when compared with control fibroblasts. CONCLUSION: These findings indicate that TGF-beta1 induces the release of EMMPRIN that activates beta-catenin/canonical Wnt signaling pathway. EMMPRIN overexpression induces an anti-apoptotic and pro-fibrotic phenotype in lung fibroblasts that may contribute to the persistent fibro-proliferative state seen in IPF. PMID- 26887534 TI - Incomplete Cor Triatriatum Dexter and Its Clinical and Technical Implications in Interatrial Shunt Device-Based Closure: An Intracardiac Echocardiography Study. AB - OBJECTIVES: Cor triatriatum dexter (CTD) is a congenital anomaly in which the right atrium is divided into two parts by a membrane or fibromuscular band. Incomplete separation of the right atrium may occur when prominent venous valve remnants such as Eustachian valve (EV) or Chiari network (CN) incompletely divided the right atrium (incomplete CTD-iCTD). We sought to assess the incidence of EV/CN and iCTD and its clinical and technical implications in patients submitted to interatrial shunt transcatheter closure. DESIGN: Retrospective analysis of single center registry. SETTING: Secondary referral center. PATIENTS: Five hundred eighty consecutive patients (mean age 44 +/- 15.5 years, 385 females) who had been submitted over a 12 years period to intracardiac echocardiography-aided interatrial shunt catheter-based closure. OUTCOMES MEASURES: Prevalence of iCTD and EV/CN, shunt grade, right ventricle diameter, incidence of intraprocedural complications. RESULTS: In patients with PFO, a prominent EV or a large CN and iCTD have been diagnosed in was diagnosed on ICE in 51.1% and 5.2%, respectively. In ASD patients, a prominent EV or a large CN and iCTD were apparent in 13.7% and 5.6%, respectively. PFO patients with iCTD had more frequently a curtain pattern on TC Doppler and a larger right-to-left shunt graded than prominent EV/CN patients and patients without. ASD patients with iCTD had larger right ventricle diameter than both ASD patients with EV/CN and patients without. iCTD was associated with 45.1% of patients with intraoperative complications. CONCLUSIONS: iCTD are not so infrequently observed by ICE during interatrial shunt closure procedure. Presence of this peculiar structure should be taken in account during device-based procedure in the right atrium. PMID- 26887533 TI - A 16-channel combined loop-dipole transceiver array for 7 Tesla body MRI. AB - PURPOSE: To develop a 16-channel transceive body imaging array at 7.0 T with improved transmit, receive, and specific absorption rate (SAR) performance by combining both loop and dipole elements and using their respective and complementary near and far field characteristics. METHODS: A 16-channel radiofrequency (RF) coil array consisting of eight loop-dipole blocks (16LD) was designed and constructed. Transmit and receive performance was quantitatively investigated in phantom and human model simulations, and experiments on five healthy volunteers inside the prostate. Comparisons were made with 16-channel microstrip line (16ML) and 10-channel fractionated dipole antenna (10DA) arrays. The 16LD was used to acquire anatomic and functional images of the prostate, kidneys, and heart. RESULTS: The 16LD provided > 14% improvements in the signal to-noise ratio (SNR), peak B1+, B1+ transmit, and SAR efficiencies over the 16ML and 10DA in simulations inside the prostate. Experimentally, the 16LD had > 20% higher SNR and B1+ transmit efficiency compared with other arrays, and achieved up to 51.8% higher peak B1+ compared with 10DA. CONCLUSION: Combining loop and dipole elements provided a body imaging array with high channel count and density while limiting inter-element coupling. The 16LD improved both near and far-field performance compared with existing 7.0T body arrays and provided high-quality MRI of the prostate kidneys and heart. Magn Reson Med 77:884-894, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26887536 TI - Effect of postprandial gum chewing on diet-induced thermogenesis. AB - OBJECTIVE: To examine the effect of postprandial gum chewing on diet-induced thermogenesis (DIT). METHODS: Twelve healthy normal-weight males completed four trials on four different days. They chewed a 621-kcal test meal for as long as possible and as many times as possible in the slow-eating trials, while they consumed the same meal as rapidly as possible in the rapid-eating trials. In the gum-chewing trials, they chewed a 3-kcal gum for 15 min after the meal. In the non-gum-chewing trials, they consumed 3 kcal of sugar with the test meal instead of chewing the gum. DIT was calculated based on the oxygen uptake, body mass, and postprandial increments in energy expenditure above the baseline as measured before each trial. RESULTS: DIT was significantly greater in the gum-chewing trials than in the non-gum-chewing trials for both rapid-eating and slow-eating trials. The difference in DIT between rapid-eating and slow-eating trials was greater than that between non-gum-chewing and gum-chewing trials. CONCLUSIONS: Postprandial gum chewing enhanced DIT, but the effect of gum chewing on DIT did not exceed that of slow eating when consuming a meal. PMID- 26887535 TI - Descriptive analysis of high birth prevalence rate geographical clusters of congenital anomalies in South America. AB - BACKGROUND: The birth prevalence rate (BPR) of congenital anomalies (CAs) is heterogeneous and exhibits geographical and sociocultural variations throughout the world. In South America (SA), high birth prevalence regions of congenital anomalies have been observed. The aim of this study was to identify, describe, and characterize geographical clusters of congenital anomalies in SA. METHODS: This observational descriptive study is based on clinical epidemiological data registered by the Latin-American Collaborative Study of Congenital Malformations network. Between 1995 and 2012, a total of 25,082 malformed newborns were ascertained from 2,557,424 births at 129 hospitals in SA. The spatial scan statistic was used to determine geographical regions with high BPR of CAs. The BPR was obtained with a Poisson regression model. Odds ratios were estimated for several risk factors inside the geographical clusters. RESULTS: We confirmed the existence of high BPR regions of CAs in SA. Indicators of low socioeconomic conditions, such as a low maternal education, extreme age childbearing, infectious diseases, and medicine use during pregnancy were detected as risk factors inside these regions. Native and African ancestries with high frequency of consanguineous marriages could explain partially these high BPR clusters. CONCLUSION: The recognition of clusters could be a starting point in the identification of susceptibility genes associated with the occurrence of CA in high BPR regions. PMID- 26887537 TI - A systematic review of prevalence and impact of symptoms of pelvic floor dysfunction in identified workforce groups. AB - AIM: To investigate the prevalence and impact of symptoms of pelvic floor dysfunction in identified workforce groups. BACKGROUND: Productivity of workforce groups is a concern for ageing societies. Symptoms of pelvic floor dysfunction are associated with ageing and negatively influence psychosocial health. In the general population, lower urinary tract symptoms negatively influence work productivity. DESIGN: A systematic review of observational studies. DATA SOURCES: Electronic searches of four academic databases. Reference lists were scanned for relevant articles. The search was limited to English language publications 1990 2014. REVIEW METHODS: The Centre for Reviews and Dissemination procedure guided the review method. Data extraction and synthesis was conducted on studies where the workforce group was identified and the type of pelvic floor dysfunction defined according to accepted terminology. Quality appraisal of studies was performed using a Joanna Briggs Institute critical appraisal tool. RESULTS: Twelve studies were identified of variable quality, all on female workers. Nurses were the most frequently investigated workforce group and urinary incontinence was the most common subtype of pelvic floor dysfunction examined. Lower urinary tract symptoms were more prevalent in the studied nurses than related general populations. No included study investigated pelvic organ prolapse, anorectal or male symptoms or the influence of symptoms on work productivity. CONCLUSION: Lower urinary tract symptoms are a significant issue among the female nursing workforce. Knowledge of the influence of symptoms on work productivity remains unknown. Further studies are warranted on the impact of pelvic floor dysfunction subtypes in workforce groups. PMID- 26887538 TI - Antimicrobial activity of Butyl acetate, Ethyl acetate and Isopropyl alcohol on undesirable microorganisms in cosmetic products. AB - OBJECTIVE: The microbiological contamination risk of a cosmetic product has to be assessed by the manufacturer, according to the composition, to determine whether microbiological testing is required. Certain ingredients in cosmetic formulations help to create an environment hostile towards microbial growth. In this study, the influence on microbial survival of some solvents used in nail varnishes was evaluated. The purpose of this study was two-fold. The first was to define the thresholds to be considered for the exemption of products from microbiological testing. The second was to assess the cross-contamination risk linked to the use on successive consumers of solvent-based products in beauty salons. METHODS: Strains of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans and Trichophyton rubrum were exposed to various concentrations of ethyl acetate, butyl acetate and isopropyl alcohol in culture medium to estimate their MIC (minimum inhibitory concentration). These strains are relevant to cosmetic products as they are associated with skin and nail infections. Mixtures of the three solvents, which are characteristic of nail varnish compositions, were also tested for their cidal activity. RESULTS: Ethyl and butyl acetates had a stronger impact than isopropyl alcohol: the MIC of ethyl and butyl acetate is <=5% for all of the tested strains, whereas that of isopropyl alcohol is <=10%. Various combinations of the three solvents tested showed a significant effect on both fungal and bacterial strains (greater than 3 log reduction in 15 min for the bacterial test strains and in 30 min for T. rubrum). CONCLUSION: Products containing more than 5% ethyl or butyl acetate or more than 10% isopropyl alcohol are hostile towards microbial growth. These products can therefore be considered as microbiologically low risk during both production and use, and so do not require microbiological testing (challenge test and end product testing). Moreover, the nine tested mixtures of these three solvents - which are characteristic of nail varnish compositions - all have a high cidal activity on the tested strains within a short time. The risk of cross contamination can therefore be considered as controlled when the nail varnishes are applied on successive clients in beauty salons. PMID- 26887539 TI - [China child health care discipline: distinguishing feature and development]. PMID- 26887540 TI - [Promote screening for primary immunodeficiency disease in neonate]. PMID- 26887541 TI - [Recommendation for child growth assessment in China]. PMID- 26887542 TI - [Early recognition and screening of primary immunodeficiency diseases]. PMID- 26887543 TI - [Expert consensus on the clinical practice of vaccination of the immunocompromised populations (trial implementation): primary immunodeficiency]. PMID- 26887544 TI - [Interpretation for the expert consensus on the clinical practice of vaccination of the immunocompromised populations (trial implementation): primary immunodeficiency]. PMID- 26887545 TI - [Multi-center study on the effects of television viewing on sleep quality among children under 4 years of age in China]. AB - OBJECTIVE: To explore the current television viewing situation among children less than 4 years of age in our country and investigate effects of television viewing on sleep quality. METHOD: According to the"Hospital of Province-City County"sampling technical route, a total of 1 046 full term healthy children at the age of 4-48 months were sampled by stratified cluster random sampling method from 8 provinces in China from 2012-2013. The information of television viewing and family and personal information was investigated by Shanghai Children's Medical Center Socio-demographic Questionnaire. Brief Infant Sleep Questionnaire (BISQ) and Brief Child Sleep Questionnaire (BCSQ) were employed to assess the sleep behaviors of children 0-3 years old and over 3 years old respectively.The effects of television viewing on sleep quality were analyzed by multiple linear regression analysis. RESULT: The children's average age was (20+/-13) months, with boys accounted for 53.3% (558/1 046). The percentage of children who viewed television was 70.3% (735/1 046). Moreover, 58.7% (408/695) of infants and young children under the age of 2 viewed TV per day, and 19.9% (70/351) of 2 years and older infants and young children viewed television >=2 hours per day. With the increase of age, the percentage of children who viewed television time gradually increased (P<0.001). Child sex, geographic area, paternal education, and family structure were not associated with television viewing time among children aged 4 48 months. However, the presence of a bedroom TV(chi(2)=13.682, P=0.001) and maternal employment (chi(2)=15.053, P=0.005) were commonly correlated with long screen-watching time among children. After adjusting for age, gender, mother' education level, and working state, it was revealed by multiple linear regression analysis that television viewing was not only positively correlated with later bedtime (t=5.49, P<0.001) and shorter night sleep duration (t=-3.49, P=0.001) but also significantly associated with longer sleep onset latency (t=2.63, P=0.009). CONCLUSION: The percentage of children under 4 years of age who viewed television is very high in our country, and many infants under 6 months of age exposed to TV environment. Bedroom TV and mother full-time job were associated with higher proportion of children viewing TV. In early childhood, television viewing was positively correlated with later bedtime, shorter sleep duration and longer sleep onset latency. There is a need for parents and pediatricians to pay more attention to the behavior of children viewing TV and improve sleep quality. PMID- 26887546 TI - [Studies of the norm and psychometrical properties of the ages and stages questionnaires, third edition, with a Chinese national sample]. AB - OBJECTIVE: To introduce the Ages and Stages Questionnaires, Third Edition (ASQ 3), to China, created ASQ-Chinese (ASQ-C) and carried out studies of its national norm and the psychometrical properties in the children aged 1-66 months in the mainland of China in collaboration with the author of the ASQ System and under the authorizations from its publisher on translation, researches, publication and distribution of the ASQ-3. METHOD: The ASQ-3 questionnaires were translated and adapted into a Simplified Chinese version, the ASQ-C, with six steps such as translation, back-translation and adaptation and so on to ensure consistency with the core of the original document and to have the cultural relevance in China.A stratified cluster sampling method was utilized to recruit children aged 1-66 months with respect to demographic characteristics such as the proportion of population in each administrative region and in urban and rural areas and so on that are representative of 2010 China census data.A sample size of over 200 was collected for each ASQ-C age interval.Children were excluded from the normative sample who (1) are from communities or villages at an elevation of 2 000 m or above and(or) where simplified Chinese is not the official language, or (2) had been diagnosed as having a developmental delay by any authoritative organizations.The national normative sample for the ASQ-C had a total sample size of 4 452, sample size within each age interval ranged from 218 to 227, including 2 230 male cases and 2 222 female cases, 2 236 urban cases and 2 216 rural cases.A convenience sample was recruited from the normative sample to examine inter-rater reliability and test-retest reliability in all six administrative regions.Researchers completed the ASQ-C on the same child with their parents for 162 children for inter-rater reliability(the size of each ASQ-C age interval was 5-9); parents of 168 children completed another age-appropriate ASQ-C for test retest reliability during 10-15 days after they completed the normative ASQ-C(The size of each ASQ-C age interval is 6-10). Another convenience sample was recruited from the follow-up of low birth weight infants for the concurrent validity of the ASQ-C in comparison with the Beijing Gesell.Parents of 198 children completed age-appropriate ASQ-C and professional administered to the children with the Beijing Gesell.In the ASQ-C norm and test-retest reliability, parents completed the age-appropriate ASQ-C, independently or with needed assistance. In inter-rater reliability, researchers completed the same ASQ-C after parents. In validity test, after parents completing age-appropriate ASQ-C, professional tested children with the Beijing Gesell.Data were analyzed using SPSS version 13.0 software.The mean and standard deviation of the national normative sample were calculated, reliability and validity of the ASQ-C was examined. RESULT: The demographic characteristics of this Chinese sample match the 2010 China census data on gender, urban or rural location, and family income.All 20 intervals of the ASQ-C were standardized on 21 national normative samples.Cronbach's alpha coefficient for the whole measure was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two raters was 0.8.The Pearson correlation coefficient between the ASQ-C total scores of the two times was 0.8 (all P<0.000 1). The sensitivity of ASQ-C was 87.50% and the specificity of ASQ-C was 84.48%.The percentage of the agreement between the ASQ-C and the Beijing Gesell was 84.74%. CONCLUSION: These findings indicate that the ASQ-C is a reliable and valid measure with a representative national sample aged 1-66 months.It can be used to screen and monitor the development of children in the mainland of China. PMID- 26887547 TI - [Relationship between energy intake and catch-up growth in full-term small-for gestational-age infants under 6 months of age]. AB - OBJECTIVE: To explore the relationship between nutrition and catch-up growth in full-term small-for-gestational-age infants under 6 months of age. METHOD: A prospective cohort study was conducted to collect clinical data of full-term small for gestational-age infants (SGA) and full-term appropriate-for-gestational age infants (AGA) from the Department of Health Care of the Children's Hospital of Chongqing Medical University. According to inclusion criteria, between February 2014 and April 2015, the infants were divided into three groups: AGA, SGA with catch-up growth (DeltaSDS of weight>=0.67), and SGA with no catch-up growth (DeltaSDS <0.67). DeltaSDS was the DeltaZ of weight, calculated using the standard deviation of the dispersion method (Z score). Chi-square was used to compare differences in feeding patterns between the catch-up growth and no catch up growth groups. Analysis of variance was used to compare differences between the three groups in daily energy intake and protein to energy ratios. RESULT: Totally 180 SGA infants within 6 months of age were enrolled, among whom 63 were male, 117 were female; and 48 AGA infants were enrolled, among whom 19 were male, 29 were female. There were no significant differences in the feeding patterns (breast feeding, partial breast feeding or full formula feeding) of SGA catch-up and SGA no catch-up groups at 1, 3 or 6 months during the first year (43 (75.4%) vs. 75 (61.0%), 7 (12.3%) vs. 25 (20.3%), 7 (12.3%) vs. 23 (18.7%) at 1 month, 70 (66.7%) vs. 39 (53.4%), 13 (12.4%) vs. 12 (16.4%), 22 (21.0%) vs. 22 (30.1%) at 3 months, 30 (31.6%) vs. 16 (23.5%), 14 (14.7%) vs. 12 (17.6%), 51 (53.7%) vs. 40 (58.8%) at 6 months, chi(2)=3.263, 3.207, 1.308 respectively, all P>0.05). The total daily energy intake (kJ/d) of the SGA no catch-up group was significantly lower than that of the AGA group at 1, 3 and 6 months of age (1 668+/-350 vs. 1 841+/-426, 1 889+/-276 vs. 2 330+/-379, 2 175+/-349 vs. 2 556+/-354, respectively, all P<0.05). It was also significantly lower than that of the SGA catch-up group at 3 months (1 889+/-276 vs. 2 118+/-361, P<0.05). The total daily energy intake of the SGA catch-up group was significantly lower than that of the AGA group at 3 and 6 months (2 118+/-361 vs. 2 330+/-379, 2 336+/-374 vs. 2 556+/ 354, respectively, all P<0.05). The average daily energy intake (kJ/(kg.d)) of the SGA no catch-up group was significantly greater than that of the SGA catch-up and AGA groups at 1 and 6 months (483+/-113 vs. 413+/-79 vs. 407+/-82, 343+/-52 vs. 321+/-56 vs. 310+/-47, respectively, all P<0.05). However, there was no significant difference between the SGA catch-up group and AGA group (all P>0.05). The protein to energy ratio(g/100 kJ)of the SGA no catch-up group was significantly higher than that of the SGA catch-up and AGA groups at 6 months (0.59+/-0.09 vs.0.51+/-0.07 vs. 0.50+/-0.07, P<0.05). There was no significant difference between the SGA catch-up group and AGA group (all P>0.05). Differences in energy intake at 1, 3 and 6 months were also compared between the SGA catch-up and SGA no catch-up groups using repeated measures analysis of variance.The results suggested the total daily energy intake in the SGA catch-up group within 6 months was higher than the SGA no catch-up group (F=7.512, P<0.05), but there were no significant differences in average daily energy intake (F=0.345) or protein to energy ratio (F=0.436) between the two groups (all P>0.05). CONCLUSION: There was no relationship between catch-up growth and feeding patterns or average daily energy intake of full-term small for gestational age infants under 6 months of age. PMID- 26887548 TI - [Clinical features and genotype analysis of 132 patients with Wiskott-Aldrich syndrome]. AB - OBJECTIVE: To investigate the clinical and immunological laboratory features, gene mutations, treatment and prognosis in children with Wiskott-Aldrich syndrome (WAS). METHOD: The clinical, laboratory characteristics, treatment and prognosis of 132 children with WAS, who visited Children's Hospital of Chongqing Medical University from April 2000 to June 2015, were analyzed retrospectively. RESULT: All patients were male. The median age of disease onset was 15 days and the median age at diagnosis was 10 months. Of the 132 cases, 112 had classic WAS, 20 had X-linked thrombocytopenia (XLT). The median platelet count was 23*10(9)/L. All cases had the clinical characteristics of WAS including bleeding, eczema, and being susceptible to infection. The initial symptoms include hemorrhage (75.0%) and eczema (16.7%). Twenty-one cases had autoimmune diseases and one patient had leukemia. WAS protein (WASP) expression in 115 cases were measured by flow cytometry, 88 cases were negative, in 12 cases WASP decreased, in 5 cases it was normal, 10 cases had bimodal distribution. Eighty-one kinds of mutations were found in 122 families, including eight kinds of hot-spot mutations, which were 290 C> N / 291G> N (R86C / H / L), 665 C> T (R211X), 155 C> T (R41X), 168 C> T (T45 M), IVS1+ 1 g> t/ a, IVS6 + 5 g> a, IVS8 + 1 g> a and IVS8 + 1to + 6del gtga. Meantime, 29 kinds of novel mutations were found, which were 321T>C, 415C>A, 471C>T, 102-105delC, 521 del C, 1330 del A, IVS2-2 a>c, 168 C>A/1412 C> T, exon1-2 del/1412 C>T, and so on. The proportion of CD3(+) T cells (31.3%), helper T cells (37.3%) and cytotoxic T cells (38.6%) in the peripheral blood declined. The serum levels of IgG (51.1%), IgA (43.3%) and IgE (40.0%) increased, IgM (25.6%) decreased. Of the 132 cases, 72 remain survived, of whom 36 cases received hematopoietic stem cell transplantation (HSCT), 14 patients with classic WAS received intravenous immunoglobulin (IVIG) therapy. With regular IVIG therapy, the frequency of infections was reduced and the patients' symptoms were improved. CONCLUSION: The clinical characteristics of Wiskott-Aldrich syndrome were early age of onset, microthrombocytopenia, eczema and recurrent infections. The proportion of T lymphocyte declined, the serum levels of IgG, IgA, and IgE increased, and level of IgM decreased in a part of patients. The detection of WAS gene mutation and WAS protein detection was the key diagnostic methods. Regular IVIG can gain more time for children who will receive HSCT and improve their quality of life. PMID- 26887549 TI - [A collaborative study of children with lymphoblastic non-Hodgkin's lymphoma in China]. AB - OBJECTIVE: To evaluate the feasibility of conducting a collaborative study and efficacy of lymphoblastic non-Hodgkin's lymphoma (LBL) treatment protocols in children with LBL in China retrospectively and to explore the clinical and prognostic features as well as treatment response of LBL, in order to better regulate the treatment for further improving the prognosis. METHOD: Seven tertiary referral centers for childhood cancer actively participated in this study. Shanghai Children's Medical Center (SCMC) 2007, SCMC-2011 and NHL-2010 protocols of treatment were modified based on BFM-90/95 regimen originated from Germany. SCMC-2007 and SCMC-2011 were used in Shanghai Children's Medical Center and NHL-2010 was used in other centers. Uniform data collection forms were sent out to all the centers and collected back via e-mail. The clinical data were then analyzed with primary focus on clinical presentations, and laboratory findings. Kaplan-Meier method was used to compare the survival rates between groups, while multiple factors logistic regression was used to identify the prognostic/relapse factors. RESULT: (1) A total of 96 patients were recruited. The median age at diagnosis was 8.6 (1.1-16.2) years. The male-to-female ratio was 3.2:1. (2) The immunophenotype was T-cell LBL in 77 patients (80%) and precursor B-cell LBL in 19 patients (20%), respectively. According to St. Jude staging classification, 6 patients (6%) were divided into stage I, 6 patients (6%) into stage II, 51 patients (53%) into stage III, 32 patients (33%) into stage IV and 1 patient with isolated bone involvement. (3) With a median follow up of 21 months (0.3-60.7 months), the 2-year overall survival (OS) rates and event-free survival (EFS) rates were (89+/-3)% and (68+/-5)%, respectively, and the 5-year probability of OS and EFS were (88+/-4)% and (64+/-6)%, respectively in all patients. Out of all, 23 patients received SCMC-2007 protocol, 15 patients received SCMC-2011 protocol and 58 patients received NHL-2010 protocol. The 2-year OS and EFS were (91+/-6)% and (70+/-10)% in SCMC-2007 study, 100% and (92+/-8)% in SCMC-2011 study, (83+/-6)% and (72+/-6)% in NHL-2010 study, respectively. For patients with complete response on day 33, the 2-year EFS was (77+/-6)% compared with (17+/ 10)% for patients with incomplete response (P<0.005). (4) In 13 patients (20%) the disease relapsed. The median relapse time range was 8 months (1-31 months). Six patients suffered from progressive disease. Logistic regression analysis showed that incomplete response on days 33 was an independent unfavorable prognostic factor (OR=4.138, P=0.035). CONCLUSION: Despite the apparent existence of gap between China and International states in the diagnostic and treatment approaches towards childhood LBL in China, with implementation of further modification of treatment protocols to strengthen cooperation between domestic tertiary centers, the long-term survival rate and reduction of recurrence of childhood LBL in China can be markedly improved. PMID- 26887550 TI - [Clinical and genetic analysis for two children with congenital disturbance of glycosylation with PMM2 gene mutations]. AB - OBJECTIVE: To analyze the clinical and PMM2 gene mutation features of congenital disturbance of glycosylation caused by PMM2 gene mutation (PMM2-CDG, previously known as CDG 1a). METHOD: The clinical data of two Chinese patients who were clinically diagnosed as PMM2-CDG at neurology department of Beijing Children's Hospital in 2012 were retrospectively collected. The gene mutations were identified by Sanger sequencing. RESULT: Both patients were female, aged 1 year and 1 month and 8 months respectively. The main clinical features of the two cases were developmental delay after birth, chronic diarrhea and metabolic acidosis, associated with elevated serum transaminases, and decreased antithrombin III activity. Physical examination showed esotropia, inverted nipples, and abnormal subcutaneous fat pads. The cranial MRI showed cerebellar atrophy. Both cases were treated with occupational therapy, physical therapy and speech therapy. The development was gradually improved but also delayed as compared with normal peers during follow-up for more than 3 years. Genetic analysis showed that patient 1 was compound heterozygous for c. 422G>A(p.Arg141His), which was reported for known pathogenic mutation, and c. 669C>A(p.Asp223Glu), was a new mutation. The patient 2 showed compound heterozygous mutation for c. 634A>G (p.Met212Val)and c. 713G>C(p.Arg238Pro), which were both new mutations. CONCLUSION: PMM2-CDG is a rare metabolic disease, and the diagnosis should be considered in a child with developmental delay, elevated serum transaminases, decreased antithrombin III activity, inverted nipples, abnormal subcutaneous fat pads, esotropia, and cerebellar atrophy on MRI. It can be confirmed by PMM2 gene analysis. PMID- 26887551 TI - [Analysis of clinical characteristics of the 12 cases of neonatal dengue fever in Guangzhou in 2014 and literatures review]. AB - OBJECTIVE: To explore the clinical manifestations and laboratory examination characteristics of neonatal dengue fever. METHOD: A retrospective analysis of 12 cases of neonatal dengue fever treated in the Guangdong Women and Children's Hospital and Guangzhou Women and Children's Medical Center was conducted, and related literature was reviewed. RESULT: Twelve cases of neonatal dengue fever included 9 males and 3 females; their age was 30 min after birth to 29 d, the age of onset was 30 min-24 d. (1) CLINICAL FEATURES: fever was present in 11 cases, rash in 6 cases, bleeding in 1 case, jaundice in 5 cases, cough in 1 case, coagulopathy in 2 cases. (2) Mothers' perinatal conditions: 7 mothers were confirmed to have dengue fever, 2 mothers had suspected dengue fever, and in 3 mothers the dengue fever was excluded. Eight mothers prenatally had fever. (3) LABORATORY TESTS: Thrombocytopenia was found in 11 cases (19*10(9)-156*10(9)/L), activated partial thromboplastin time prolonged in 11 cases (44.0-89.8 s), fibrinogen decreased in 5 cases (1.17-3.02 g/L), aspartate aminotransferase (AST) increased in 5 cases (28-78 U/L), creatine kinase (CK-MB) increased in 4 cases (13-86 U/L), hypokalemia in 1 case (2.8-5.1 mmol/L ), C- reactive protein (CRP) increased in 6 cases (0.04-46.05 mg/L). (4) Treatment and prognosis: platelet transfusion was used in 2 cases, anti-infective therapy was given to 6 cases, intravenous gamma globulin treatment was used in 5 cases, hospitalization was 4 17 d, 10 cases were cured, 2 cases were discharged after condition was improved. Literature search was performed with "neonatal dengue" as keywords at Wanfang, Weipu, and CNKI, no relevant reports were found. Pubmed search was done with "neonatal dengue" and "case report" as keywords, 15 reports were retrieved during 1990 and 2014, which reported 30 cases, all acquired the disease via vertical transmission; the main clinical manifestations were fever, rash, petechiae, anemia, jaundice, tachycardia, and hepatomegaly; laboratory test: all had visible purpura due to thrombocytopenia; anti-infective treatment, platelet transfusion and symptomatic treatment were given, and all the 30 cases of infants were cured. CONCLUSION: The clinical manifestations of neonatal dengue fever are characterized by fever and the disorder of blood coagulation system. The course of disease is mild, lack of specific clinical symptoms, and the prognosis is good. Mother to infant vertical transmission of dengue virus is one of the ways of transmission. PMID- 26887553 TI - [A case of pediatric follicular lymphoma]. PMID- 26887552 TI - [Antibodies to mutated citrullinated vimentin and some associated autoantibodies in juvenile idiopathic arthritis]. AB - OBJECTIVE: To compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers. METHOD: Antibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis. RESULT: (1) The positive rate of anti-MCV antibodies, anti CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA. In the other group, the positive rate was 2.2%, 2.2%, and 6.5%. There was a significant difference between the two groups (chi(2)=8.105, 6.337, 7.036, P<0.05). The positive rate of AKA and APF were not significantly different. The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505. (2) The positive rate of anti-MCV antibodies and anti CCP antibodies were higher than other antibodies. In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P<0.05). Antibody levels were not significantly different (P>0.05) from other subtypes. (3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. CONCLUSION: The diagnostic value of anti-MCV antibodies is low for JIA. The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA. There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts. PMID- 26887554 TI - [A case report of plasmapheresis successfully treated macrophage activation syndrome in juvenile idiopathic arthritis]. PMID- 26887555 TI - [The cardiovascular changes in pediatric onset systemic lupus erythematosus]. PMID- 26887556 TI - [Relationship between the different components of executive function and obesity in children]. PMID- 26887557 TI - [Nonhomologous DNA end joining pathway defect and primary immunodeficiency diseases]. PMID- 26887558 TI - [Paracetamol treatment for patent ductus arteriosus in premature infants: a review]. PMID- 26887559 TI - [Summary of the fifth national children's syncope academic conference]. PMID- 26887560 TI - The consistent difference in red fluorescence in fishes across a 15 m depth gradient is triggered by ambient brightness, not by ambient spectrum. AB - BACKGROUND: Organisms adapt to fluctuations or gradients in their environment by means of genetic change or phenotypic plasticity. Consistent adaptation across small spatial scales measured in meters, however, has rarely been reported. We recently found significant variation in fluorescence brightness in six benthic marine fish species across a 15 m depth gradient. Here, we investigate whether this can be explained by phenotypic plasticity alone, using the triplefin Tripterygion delaisi as a model species. In two separate experiments, we measure change in red fluorescent brightness to spectral composition and ambient brightness, two central parameters of the visual environment that change rapidly with depth. RESULTS: Changing the ambient spectra simulating light at -5 or -20 m depth generated no detectable changes in mean fluorescence brightness after 4-6 weeks. In contrast, a reduction in ambient brightness generated a significant and reversible increase in mean fluorescence, most of this within the first week. Although individuals can quickly up- and down-regulate their fluorescence around this mean value using melanosome aggregation and dispersal, we demonstrate that this range around the mean remained unaffected by either treatment. CONCLUSION: We show that the positive association between fluorescence and depth observed in the field can be fully explained by ambient light brightness, with no detectable additional effect of spectral composition. We propose that this change is achieved by adjusting the ratio of melanophores and fluorescent iridophores in the iris. PMID- 26887562 TI - NMDA receptors amplify mossy fiber synaptic inputs at frequencies up to at least 750 Hz in cerebellar granule cells. AB - Neuronal integration of high-frequency signals is important for rapid information processing. Cerebellar mossy fiber axons (MFs) can fire action potentials (APs) at frequencies of more than one kilohertz. However, it is unclear whether and how the postsynaptic cerebellar granule cells (GCs) are able to process these high frequency MF inputs. Here, we measured AP firing in GCs during high-frequency MF stimulation and show that GC firing frequency increased non-linearly when MF stimulation frequency was increased from 100 to 750 Hz. To investigate the mechanisms enabling such high-frequency signaling, we analyzed the role of N methyl-d-aspartate receptors (NMDARs), which have been implicated in synaptic signaling at lower frequencies. Application of D-2-amino-5-phosphonopentanoic acid (APV), a potent inhibitor of NMDARs, strongly impaired the GC firing frequency during high-frequency MF stimulation. APV had no significant effect on single excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) evoked at 1 Hz at resting membrane potentials. However, the time course of EPSCs evoked at 1 Hz at depolarized potentials or following high-frequency MF stimulation was accelerated by APV. Thus, our results show that NMDAR-mediated currents amplify high-frequency MF inputs by prolonging the time courses of synaptic inputs, thereby causing greater synaptic summation of inputs. Hence, NMDARs support the integration of MF synaptic input at frequencies up to at least 750 Hz. Synapse 70:269-276, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26887561 TI - Who's misbehaving? Perceptions of unprofessional social media use by medical students and faculty. AB - BACKGROUND: Social media use by physicians offers potential benefits but may also be associated with professionalism problems. The objectives of this study were: 1) to examine and compare characteristics of social media use by medical students and faculty; 2) to explore the scope of self- and peer-posting of unprofessional online content; and 3) to determine what actions were taken when unprofessional content was viewed. METHODS: An anonymous, web-based survey was sent to medical students and faculty in October, 2013 at the Albert Einstein College of Medicine in Bronx, New York. RESULTS: Three-quarters of medical students reported using social media "very frequently" (several times a day), whereas less than one-third of faculty did so (p < .001). Medical students reported using privacy settings more often than faculty (96.5 % v. 78.1 %, p < .001). Most medical students (94.2 %) and faculty (94.1 %) reported "never" or "occasionally" monitoring their online presence (p = 0.94). Medical students reported self-posting of profanity, depiction of intoxication, and sexually suggestive material more often than faculty (p < .001). Medical students and faculty both reported peer-posting of unprofessional content significantly more often than self-posting. There was no association between year of medical school and posting of unprofessional content. CONCLUSION: Medical students reported spending more time using social media and posting unprofessional content more often than did faculty. PMID- 26887563 TI - Biological verification of sterilization cycles in dental clinics in Mexico. PMID- 26887564 TI - Non-invasive assessment of tear film stability with a novel corneal topographer in Indian subjects. AB - The aim of the study is to investigate the applicability of a newly developed corneal topographer in assessing tear film stability in Indian subjects. A prospective comparative study of 25 Indian subjects with dry eyes attending a tertiary eye care clinic in South India and 25 normal control subjects was conducted. The diagnosis of dry eye was made based on ocular surface disease index questionnaire. Non-invasive tear film break-up time (NI-TBUT) was measured using a new method based on a corneal topographer equipped with modified scan software. The correlations between the NI-TBUT and the traditional fluorescein tear film break-up time (F-TBUT), Schirmer I test values were determined. A total of 50 patients (100 eyes) were included. The values of NI-TBUT were significantly lower than the values of F-TBUT in both the cases (NI-TBUT 5.78 +/- 0.8 s and F TBUT 7.56 +/- 0.5 s; p < 0.02) and controls (NI-TBUT 11.66 +/- 1 s and F-TBUT 12.92 +/- 1.2 s; p < 0.01). NI-TBUT values were significantly lower than the corresponding F-TBUT values in the varying grades of dry eyes. The mean NI-TBUT values in mild dry eyes was 6.42 +/- 0.2 s, moderate dry eyes was 4.70 +/- 0.3 s and in severe dry eyes was 2.32 +/- 1.2 s. There was a significant difference in the NI-TBUT values for cases and controls (p < 0.001). There was a good correlation seen between the NI-TBUT values and the F-TBUT values, Schirmer I values and the ODSI scores. NI-TBUT was found to have a sensitivity of 86.1 % and a specificity of 81.1 % when the cut-off value was kept at 6.2 s. We investigated the performance of a non-invasive technique for measuring tear film stability to aid in the diagnosis of dry eye disease. It is a useful non-invasive objective method for the detection of dry eye, and its varying grades and may be useful in monitoring the efficacy of therapies for dry eye. PMID- 26887565 TI - Comparability of retinal thickness measurements using different scanning protocols on spectral-domain optical coherence tomography. AB - Retinal thickness measurements obtained using optical coherence tomography (OCT) play an essential role both in multi-center clinical trials and in normal clinical practice. Different scanning protocols are available on most OCT devices, and it is important to ascertain whether the retinal thickness measurements obtained from these are comparable. This study aimed to compare retinal thickness measurements between raster and radial scanning protocols using spectral-domain OCT (SD-OCT). In a prospective study, 32 healthy subjects were scanned sequentially using raster and radial protocols from a SD-OCT device. For both the raster and radial OCT scans, retinal thicknesses were measured manually subfoveally and at 12 other points at 0.5 mm intervals temporally and nasally on the horizontal OCT B-scan passing through the fovea. The retinal thickness measurements were compared using intraclass correlation (ICC) and Bland-Altman plots. Subfoveal retinal thickness was 227.0 um when measured on the raster scan and 229.2 um on the radial scan, with a mean difference of 2.2 um (P = 0.141).The ICC for agreement was 0.889 (95 % confidence interval 0.818-0.933). Similar results were observed for retinal thickness measurements at all other points, with mean differences ranging from -3.37 to 2.59 um, and ICC values ranging from 0.837 to 0.972. The retinal thickness measurements obtained by the raster and radial scans of the same SD-OCT device are comparable, with differences of less than 4 um. This is of relevance when measurements made using different OCT scan protocols are compared. PMID- 26887567 TI - Late onset dHMN II caused by c.404C>G mutation in HSPB1 gene. AB - Distal hereditary motor neuropathy (dHMN) type II is genetically heterogeneous. We report three siblings of a German family with late onset distal motor neuropathy due to the c.404C>G mutation in heat-shock 27-kDa protein 1 gene (HSPB1/HSP27). A 36-year-old mutation carrier, daughter of one sibling, did not present any clinical or electrophysiological abnormalities. The index patient (oldest brother) developed weakness of the distal lower limbs and nocturnal muscle cramps at the age of 54. After 5 years this patient developed an l-DOPA responsive hypokinetic rigid syndrome, establishing a diagnosis of Parkinson's disease. Although none of the three other mutation carriers displayed Parkinsonian signs, a pathogenic relationship with Parkinson's disease remains a possibility, based on the known molecular pathology of HSPB1. The rare pathogenic HSPB1 c.404C>G mutation may predispose for late-onset of dHMN type II. PMID- 26887566 TI - Evaluation of the anatomic and refractive differences in hyperopic anisometropia. AB - The purpose of this study was to investigate the interocular symmetry of ultrasonic biometric characteristics and anterior segment measurements between the fellow eyes of hyperopic anisometropes. Forty-two healthy hyperopic anisometropic cases (1 D mean spherical equivalent difference between eyes) without strabismus were recruited. A range of refractive and ultrasonic biometric parameters were measured in both eyes of each subject including keratometry, mean spherical equivalent, anterior chamber depth (ACD), lens thickness, vitreous depth (VD), axial length (AL), and anterior segment parameters (central corneal thickness (CCT), ACD, anterior chamber volume (ACV)) with Pentacam. Mean spherical equivalent anisometropia was 2.66 +/- 1.233 (range 1.125 and 6.25) D, and there was a strong correlation between the degree of anisometropia and the interocular difference in AL (r = 0.632, P < 0.001). A total of 61.3 % of the anisometropia was related with AL (50.7 %) and mean keratometry (10.6 %). Every 1 mm change in AL and every 1 D change in mean keratometry caused a total of 2.82 D and 2.14 D refractive difference, respectively. Among Pentacam parameters, ACD was correlated with ACV (r = 0.528; P < 0.001) and AL (r = 0.510; P = 0.001); ACV was correlated with VD (r = 0.358; P = 0.020); and CCT was correlated with ACV (r = 0.510; P = 0.001) and AL (r = 0.318; P = 0.040). Among ultrasonographic measurements, ultrasonic-ACD was correlated with CCT (r = 0.510; P = 0.001) and lens thickness (r = -0.556; P < 0.001), and VD was correlated with AL (r = 0.937, r 2 = 0.877, P < 0.001). The hyperopic and the fellow eyes displayed a high degree of interocular symmetry for the other measured parameters. AL and mean keratometry are the leading causes of hyperopic anisometropia. However, ACD as measured with Pentacam also shows difference in hyperopic anisometropic eyes. PMID- 26887568 TI - Prednisolone impairs embryonic and posthatching development and shell formation of the freshwater snail, Physa acuta. AB - The aim of the present study was to investigate the lethal and sublethal effects of prednisolone exposure on the embryonic and posthatching stage of the freshwater snail, Physa acuta. The egg masses were exposed for 14 d to prednisolone concentrations ranging from 15.6 MUg/L to 1000 MUg/L. Treatment with prednisolone at 125 MUg/L to 1000 MUg/L resulted in significant decline in growth, survival, and heart rate, as well as notable abnormalities in embryonic development. Premature embryonic hatching was observed at lower concentrations of 31.25 MUg/L and 62.5 MUg/L, whereas delayed hatching was seen at concentrations from 125 MUg/L to 1000 MUg/L. To assess impacts of prednisolone exposure on the hatched juveniles, the drug exposure was extended for another 28 d. Impairment of shell development was noted in juveniles exposed to concentrations from 62.5 MUg/L to 1000 MUg/L at the end of 42 d, which resulted in thin and fragile shells. The thickness of shells in snails exposed to 1000 MUg/L was significantly lower in comparison to those in the 15.6-MUg/L and control treatments. In addition, lower calcium concentration in shells of the exposed juvenile snails at treatments of 62.5 MUg/L to 1000 MUg/L consequently reduced their growth. The present study confirms that continuous exposure to prednisolone can result in deleterious effects on calcium deposition, resulting in shell thinning in the freshwater snail P. acuta. Environ Toxicol Chem 2016;35:2339-2348. (c) 2016 SETAC. PMID- 26887569 TI - Synthesis of chiral 2-alkanols from n-alkanes by a P. putida whole-cell biocatalyst. AB - The cytochrome P450 monooxygenase CYP154A8 from Nocardia farcinica was previously found to catalyze hydroxylation of linear alkanes (C7 -C9 ) with a high regio- and stereoselectivity. The objective of this study was to integrate CYP154A8 along with suitable redox partners into a whole-cell system for the production of chiral 2-alkanols starting from alkanes. Both recombinant Escherichia coli and Pseudomonas putida whole-cell biocatalysts tested for this purpose showed the ability to produce chiral alkanols, but a solvent tolerant P. putida strain demonstrated several advantages in the applied biphasic reaction system. The optimized P. putida whole-cell system produced ~16 mM (S)-2-octanol with 87% ee from octane, which is more than sevenfold higher than the previously described system with isolated enzymes. The achieved enantiopurity of the product could further be increased up to 99% ee by adding an alcohol dehydrogenase (ADH) to the alkane-oxidizing P. putida whole-cell systems. By using this setup for the individual conversions of heptane, octane or nonane, 2.6 mM (S)-2-heptanol with 91% ee, 5.4 mM (S)-2-octanol with 97% ee, or 5.5 mM (S)-2-nonanol with 97% ee were produced, respectively. The achieved concentrations of chiral 2-alkanols are the highest reported for a P450-based whole-cell system so far. Biotechnol. Bioeng. 2016;113: 1845-1852. (c) 2016 Wiley Periodicals, Inc. PMID- 26887571 TI - Porous LaCo1-xNixO3-delta Nanostructures as an Efficient Electrocatalyst for Water Oxidation and for a Zinc-Air Battery. AB - Perovskites have emerged as promising earth-abundant alternatives to precious metals for catalyzing the oxygen evolution reaction (OER). Herein, we report the synthesis of a series of porous perovskite nanostructures, LaCo0.97O3-delta, with systematic Ni substitution in Co octahedral sites. Their electrocatalytic activity during the water oxidation reaction was studied in alkaline electrolytes. The electrocatalytic OER activity and stability of the perovskite nanostructure was evaluated using the rotating disk electrode technique. We show that the progressive replacement of Co by Ni in the LaCo0.97O3-delta perovskite structure greatly altered the electrocatalytic activity and that the La(Co0.71Ni0.25)0.96O3-delta composition exhibited the lowest OER overpotential of 324 and 265 mV at 10 mA cm(-2) in 0.1 M KOH and 1 M KOH, respectively. This value was much lower than that of the noble metal catalysts, IrO2, Ru/C, and Pt/C. Furthermore, the La(Co0.71Ni0.25)0.96O3-delta nanostructure showed outstanding electrode stability, with no observable decrease in performance up to 114th cycle in the auxiliary linear sweep voltammetry that lasted for 10 h in chronoamperometry studies. The excellent oxygen evolution activity of the La(Co0.71Ni0.25)0.96O3-delta perovskite nanostructure can be attributed to its intrinsic structure, interconnected particle arrangement, and unique redox characteristics. The enhanced intrinsic electrocatalytic activity of the La(Co0.71Ni0.25)0.96O3-delta catalyst was correlated with several parameters, such as the electrochemical surface area, the roughness factor, and the turnover frequency, with respect to variation in the transition metals of the perovskite structure. Subsequently, La(Co0.71Ni0.25)0.96O3-delta was utilized as the air cathode in a zinc-air battery application. PMID- 26887572 TI - Erratum to: MINE: Module Identification in Networks. PMID- 26887570 TI - Stability properties of neuronal microtubules. AB - Neurons are terminally differentiated cells that use their microtubule arrays not for cell division but rather as architectural elements required for the elaboration of elongated axons and dendrites. In addition to acting as compression-bearing struts that provide for the shape of the neuron, microtubules also act as directional railways for organelle transport. The stability properties of neuronal microtubules are commonly discussed in the biomedical literature as crucial to the development and maintenance of the nervous system, and have recently gained attention as central to the etiology of neurodegenerative diseases. Drugs that affect microtubule stability are currently under investigation as potential therapies for disease and injury of the nervous system. There is often a lack of consistency, however, in how the issue of microtubule stability is discussed in the literature, and this can affect the design and interpretation of experiments as well as potential therapeutic regimens. Neuronal microtubules are considered to be more stable than microtubules in dividing cells. On average, this is true, but in addition to an abundant stable microtubule fraction in neurons, there is also an abundant labile microtubule fraction. Both are functionally important. Individual microtubules consist of domains that differ in their stability properties, and these domains can also differ markedly in their composition as well as how they interact with various microtubule-related proteins in the neuron. Myriad proteins and pathways have been discussed as potential contributors to microtubule stability in neurons. (c) 2016 Wiley Periodicals, Inc. PMID- 26887573 TI - An evaluation of the Swiss staging model for hypothermia using case reports from the literature. AB - BACKGROUND: Core body temperature is used to stage and guide the management of hypothermic patients, however obtaining accurate measurements of core temperature is challenging, especially in the pre-hospital context. The Swiss staging model for hypothermia uses clinical indicators to stage hypothermia. The proposed temperature range for clinical stage 1 is <35-32 degrees C (95-90 degrees F), for stage 2, <32-28 degrees C (<90-82 degrees F) for stage 3, <28-24 degrees C (<82-75 degrees F), and for stage 4 below 24 degrees C (75 degrees F). However, the evidence relating these temperature ranges to the clinical stages needs to be strengthened. METHODS: Medline was used to retrieve data on as many cases of accidental hypothermia (core body temperature <35 degrees C (95 degrees F)) as possible. Cases of therapeutic or neonatal hypothermia and those with confounders or insufficient data were excluded. To evaluate the Swiss staging model for hypothermia, we estimated the percentage of those patients who were correctly classified and compared the theoretical with the observed ranges of temperatures for each clinical stage. The number of rescue collapses was also recorded. RESULTS: We analysed 183 cases; the median temperature for the sample was 25.2 degrees C (IQR 22-28). 95 of the 183 patients (51.9%; 95% CI = 44.7% 59.2%) were correctly classified, while the temperature was overestimated in 36 patients (19.7%; 95% CI = 13.9%-25.4%). We observed important overlaps among the four stage groups with respect to core temperature, the lowest observed temperature being 28.1 degrees C for Stage 1, 22 degrees C for Stage 2, 19.3 degrees C for Stage 3, and 13.7 degrees C for stage 4. CONCLUSION: Predicting core body temperature using clinical indicators is a difficult task. Despite the inherent limitations of our study, it increases the strength of the evidence linking the clinical hypothermia stage to core temperature. Decreasing the thresholds of temperatures distinguishing the different stages would allow a reduction in the number of cases where body temperature is overestimated, avoiding some potentially negative consequences for the management of hypothermic patients. PMID- 26887574 TI - Delayed consequences of extremely low-frequency magnetic fields and the influence of adverse environmental conditions on roach Rutilus rutilus embryos. AB - This study presents data collected over a 6 year period on the effects of extremely low-frequency magnetic fields (MFs) (1.4-1.6 uT, 500 Hz and 1.4-1.6 uT, 72.5 Hz) and MFs in combination with other environmental stressors (elevated temperature, 0.01 mg l(-1) trichlorfon, 0.01 mg l(-1) copper sulphate pentahydrate) on roach Rutilus rutilus embryos. Effects were studied during different stages of early development. Rutilus rutilus were raised in ponds for 4 months after exposure to MFs. The mass, standard length (LS ) and morphological characteristics of underyearlings which were exposed as embryos were recorded. An increase in embryo mortality and a decrease in LS and mass indices in underyearlings were noted after they had been exposed to a combination of MFs and different adverse environmental factors. In addition, exposure to MFs led to changes in the total number of vertebrae and the number of seismosensory system openings in the mandibular bones of underyearlings. MFs of different frequency caused both increases (500 Hz) and decreases (72.5 Hz) in morphological diversity. The stressors used in this study, however, did not increase the fluctuating asymmetry of bilateral morphological characteristics. The possible microevolutionary effects of exposure to MFs alone and in combination with other adverse environmental factors upon natural fish populations are discussed. PMID- 26887575 TI - Assessment of the H-reflex at two contraction levels before and after fatigue. AB - The aim of the present study was to compare the H-reflex evoked at rest and at 20% maximal voluntary contraction (MVC) prior to and after fatiguing the lateral gastrocnemius (LG). The maximal H-reflex and M-wave were recorded in the LG, and soleus (SOL). Electrical evoked potentials were delivered to the posterior tibial nerve when muscles were inactivated and at 20% MVC. After fatigue, the Hmax /Mmax ratio of the fatigued LG was increased for both contraction levels (rest and 20% MVC) and remained unaltered for non-fatigued SOL. Before fatigue, the Hmax /Mmax ratio of SOL was enhanced at rest compared with the Hmax /Mmax ratio at 20% MVC. No differences were observed for LG. Fatigue of a single muscle leads to increased spinal reflex activity of the homonymous muscle. Contrary to previous recommendations in the literature, there appears to be no benefit with regard to the H-reflex amplitude in evoking electrical potentials during constant voluntary contractions at 20% MVC compared with inactivated muscles. The observed difference in SOL prior to fatigue was most likely due to hyperpolarization of the muscle fiber membrane. PMID- 26887577 TI - Dietary antioxidant capacity and all-cause and cause-specific mortality in the E3N/EPIC cohort study. AB - PURPOSE: The cellular oxidative stress (balance between pro-oxidant and antioxidant) may be a major risk factor for chronic diseases. Antioxidant capacity of human diet can be globally assessed through the dietary non-enzymatic antioxidant capacity (NEAC). Our aim was to investigate the relationship between the NEAC and all-cause and cause-specific mortality, and to test potential interactions with smoking status, a well-known pro-oxidant factor. METHODS: Among the French women of the E3N prospective cohort study initiated in 1990, including 4619 deaths among 1,199,011 persons-years of follow-up. A validated dietary history questionnaire assessed usual food intake; NEAC intake was estimated using a food composition table from two different methods: ferric ion reducing antioxidant power (FRAP) and total radical-trapping antioxidant parameter (TRAP). Hazard ratio (HR) estimates and 95 % confidence intervals (CI) were derived from Cox proportional hazards regression models. RESULTS: In multivariate analyses, FRAP dietary equivalent intake was inversely associated with mortality from all causes (HR for the fourth vs. the first quartile: HR4 = 0.75, 95 % CI 0.67, 0.83, p trend < 0.0001), cancer, and cardiovascular diseases. Similar results were obtained with TRAP. There was an interaction between NEAC dietary equivalent intake and smoking status for all-cause and cardiovascular disease mortality, but not cancer mortality (respectively, for FRAP, p inter = 0.002; 0.013; 0.113, results were similar with TRAP), and the association was the strongest among current smokers. CONCLUSION: This prospective cohort study highlights the importance of antioxidant consumption for mortality prevention, especially among current smokers. PMID- 26887576 TI - Effect of aqua-cycling on pain and physical functioning compared with usual care in patients with knee osteoarthritis: study protocol of a randomised controlled trial. AB - BACKGROUND: Over the last decade aquatic exercise has become more and more popular. One of the latest trends is aqua-cycling, where participants sit on a water-resistant stationary bike and, while immersed chest deep in the water, combine continuous cycling with upper body exercises that utilise water resistance. Since stationary cycling and aquatic exercises are frequently recommended to patients with knee osteoarthritis, combining both would seem an obvious step, and an aqua-cycling exercise programme for patients with knee osteoarthritis has indeed been developed. This study protocol gives a detailed description of the exercise programme and the methodology of a study to compare this programme with treatment involving usual care only. METHODS: The study is a single-blind, parallel-group, randomised controlled trial of Maastricht University Medical Centre+, the Netherlands. INCLUSION CRITERIA: knee pain of four to seven on a 10-point pain rating scale; a Kellgren/Lawrence score between one to three; ability to cycle; good mental health; sufficient language skills; indication for physical therapy in conjunction with impairments due to OA. EXCLUSION CRITERIA: any contra-indication for aquatic exercise; planned total knee replacement; corticosteroid injection <3 months and/or hyaluronic acid injection <6 months; severe joint complaints (other than knee joint); symptomatic and radiological apparent hip OA; inflammatory joint diseases; inability to safely enter and exit the pool; fear of water. Participants will receive two 45 min moderate intense aqua-cycling sessions weekly over a period of 12 weeks in addition to usual care or usual care only. Usual care consists of an individual intervention plan comprising lifestyle recommendations, medication routine and referral to a physical therapist. Participants will be assessed at baseline, and at 12 and 24 weeks after baseline. The primary outcome is self-reported knee pain and physical functioning. Secondary outcomes are lower limb muscle strength, functional capacity, self-reported disease severity, physical activity level, quality of life, self-efficacy and fear of movement. Daily diaries will collect information on knee pain, physical functioning, level of physical activity, pain medication routine and physical therapy (control group only) or exercise participation over two 30-day periods (during the intervention period). DISCUSSION: To our knowledge the present study is the first randomised controlled trial evaluating the effects of aqua-cycling in the pre-surgical stage of knee osteoarthritis. This trial will demonstrate if the newly designed aqua-cycling intervention, in supplement to usual care, can help to improve impairments due to knee osteoarthritis. TRIAL REGISTRATION: Netherlands Trial Register NTR3766 (21 12-2012). PMID- 26887578 TI - Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology. AB - Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 MUm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status. PMID- 26887579 TI - Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants. AB - A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of alpha-glucosidase (AG) enzyme onto amine functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p nitrophenyl-alpha-D-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau (Ehretis laevis), Cemumar (Micromelum pubescens), and Kedondong (Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 MUA, and the inhibition detection limit was 0.253 MUA. The biosensor exhibited good sensitivity (0.422 MUA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 degrees C. PMID- 26887581 TI - Comparative study of wavelet denoising in myoelectric control applications. AB - Here, the wavelet analysis has been investigated to improve the quality of myoelectric signal before use in prosthetic design. Effective Surface Electromyogram (SEMG) signals were estimated by first decomposing the obtained signal using wavelet transform and then analysing the decomposed coefficients by threshold methods. With the appropriate choice of wavelet, it is possible to reduce interference noise effectively in the SEMG signal. However, the most effective wavelet for SEMG denoising is chosen by calculating the root mean square value and signal power values. The combined results of root mean square value and signal power shows that wavelet db4 performs the best denoising among the wavelets. Furthermore, time domain and frequency domain methods were applied for SEMG signal analysis to investigate the effect of muscle-force contraction on the signal. It was found that, during sustained contractions, the mean frequency (MNF) and median frequency (MDF) increase as muscle force levels increase. PMID- 26887580 TI - Laser biospectroscopy and 5-ALA fluorescence navigation as a helpful tool in the meningioma resection. AB - 5-aminolevulinic acid (5-ALA) is a natural precursor of protoporphyrin IX (PP IX), which possesses fluorescent properties and is more intensively accumulated in tumor cells than in normal tissue. Therefore, the use of 5-ALA in the surgical treatment of intracranial tumors, particularly gliomas, has gained popularity in the last years, whereas its use in other intracranial pathological entities including meningiomas has been reported occasionally. This study describes a series of 28 patients with intracranial meningiomas, who were administered 5-ALA for a better visualization of tumor boundaries. Twelve patients underwent also laser spectroscopic analysis in order to confirm the visual impression of tumor tissue visualization. Bone infiltration was readily demonstrated. In one case, the tumor recurrence could have been prevented by removal of a tumor remnant, which would possibly have been better recognized if spectroscopic analysis had been used. Fluorescent navigation (FN) is a useful method for maximizing the radicality of meningioma surgery, particularly if the tumor infiltrates the bone, the skull base, and/or the surrounding structures. PMID- 26887583 TI - Integrative genomic testing of cancer survival using semiparametric linear transformation models. AB - The wide availability of multi-dimensional genomic data has spurred increasing interests in integrating multi-platform genomic data. Integrative analysis of cancer genome landscape can potentially lead to deeper understanding of the biological process of cancer. We integrate epigenetics (DNA methylation and microRNA expression) and gene expression data in tumor genome to delineate the association between different aspects of the biological processes and brain tumor survival. To model the association, we employ a flexible semiparametric linear transformation model that incorporates both the main effects of these genomic measures as well as the possible interactions among them. We develop variance component tests to examine different coordinated effects by testing various subsets of model coefficients for the genomic markers. A Monte Carlo perturbation procedure is constructed to approximate the null distribution of the proposed test statistics. We further propose omnibus testing procedures to synthesize information from fitting various parsimonious sub-models to improve power. Simulation results suggest that our proposed testing procedures maintain proper size under the null and outperform standard score tests. We further illustrate the utility of our procedure in two genomic analyses for survival of glioblastoma multiforme patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887582 TI - The Neuroprotective Effects of Justicidin A on Amyloid Beta25-35-Induced Neuronal Cell Death Through Inhibition of Tau Hyperphosphorylation and Induction of Autophagy in SH-SY5Y Cells. AB - Justicidin A is a structurally defined arylnaphthalide lignan, which has been shown anti-cancer activity; however, the neuroprotective effect of justicidin A is still untested. In this study, we investigated the action of justicidin A on amyloid beta (Abeta)25-35-induced neuronal cell death via inhibition of the hyperphosphorylation of tau and induction of autophagy in SH-SY5Y cells. Pretreatment with justicidin A significantly elevated cell viability in cells treated with Abeta25-35. Western blot data demonstrated that justicidin A inhibited the Abeta25-35-induced up-regulation the levels of hyperphosphorylation of tau in SH-SY5Y cells. In addition, treatment with justicidin A significantly induced autophagy as measured by the increasing LC3 II/I ratio, an important autophagy marker. These studies showed that justicidin A inhibited activity of glycogen synthase kinase-3beta (GSK-3beta), which is an important kinase in up stream signaling pathways; inhibited hyperphosphorylation of tau in AD; and enhanced activity of AMP-activated protein kinase (AMPK), which is the key molecule for both hyperphosphorylation of tau and induction of autophagy. These data provide the first evidence that justicidin A protects SH-SY5Y cells from Abeta25-35-induced neuronal cell death through inhibition of hyperphosphorylation of tau and induction of autophagy via regulation the activity of GSK-3beta and AMPK, and they also provide some insights into the relationship between tau protein hyperphosphorylation and autophagy. Thus, we conclude that justicidin A may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for AD. PMID- 26887585 TI - A randomized controlled trial of two mail-based lifestyle interventions for breast cancer survivors. AB - PURPOSE: Although breast cancer survivors' lifestyle choices affect their subsequent health, a majority do not engage in healthy behaviors. Because treatment end is a "teachable moment" for potentially altering lifestyle change for breast cancer survivors, we developed and tested two mail-based interventions for women who recently completed primary treatment. METHODS: One hundred seventy three survivors were randomly assigned to (1) Targeting the Teachable Moment (TTMI, n = 57), (2) Standard Lifestyle Management (SLM, n = 58), or (3) usual care (UC, n = 58) control group. Participants who were assigned to TTMI and SLM received relevant treatment materials biweekly for 4 months. Participants were assessed at baseline (T1, before randomization), post-treatment (T2, 4 months), and follow-up (T3, 7 months). Fruit and vegetable (F/V) intake, fat intake, and moderate-to-vigorous physical activity (MVPA) were assessed. RESULTS: Results showed promise for these mail-based interventions for changes in health behaviors: Survivors in TTMI (+.47) and SLM (+.45) reported increased F/V intake, whereas those in UC (-.1) reported decreased F/V intake from T1 to T2. Changes in minutes of MVPA from T1 to T2 were higher in SLM than UC and marginally higher in TTMI than UC. However, these differences were due to decreased MVPA in UC rather than increased MVPA in the intervention groups. There were no group differences regarding fat intake. Survivors reported high satisfaction and preference for mail-based interventions, supporting feasibility. CONCLUSIONS: Mail-based lifestyle interventions for breast cancer survivors may benefit F/V intake and physical activity. Further testing and optimizing of these interventions is warranted. PMID- 26887584 TI - AllergenOnline: A peer-reviewed, curated allergen database to assess novel food proteins for potential cross-reactivity. AB - SCOPE: Increasingly regulators are demanding evaluation of potential allergenicity of foods prior to marketing. Primary risks are the transfer of allergens or potentially cross-reactive proteins into new foods. AllergenOnline was developed in 2005 as a peer-reviewed bioinformatics platform to evaluate risks of new dietary proteins in genetically modified organisms (GMO) and novel foods. METHODS AND RESULTS: The process used to identify suspected allergens and evaluate the evidence of allergenicity was refined between 2010 and 2015. Candidate proteins are identified from the NCBI database using keyword searches, the WHO/IUIS nomenclature database and peer reviewed publications. Criteria to classify proteins as allergens are described. Characteristics of the protein, the source and human subjects, test methods and results are evaluated by our expert panel and archived. Food, inhalant, salivary, venom, and contact allergens are included. Users access allergen sequences through links to the NCBI database and relevant references are listed online. Version 16 includes 1956 sequences from 778 taxonomic-protein groups that are accepted with evidence of allergic serum IgE-binding and/or biological activity. CONCLUSION: AllergenOnline provides a useful peer-reviewed tool for identifying the primary potential risks of allergy for GMOs and novel foods based on criteria described by the Codex Alimentarius Commission (2003). PMID- 26887586 TI - Electronic real-time assessment of patient-reported outcomes in routine care first findings and experiences from the implementation in a comprehensive cancer center. AB - PURPOSE: Cancer patients suffer from a variety of physical and mental complaints. Since physician assessment of symptoms seems insufficient to reveal the complete range of patients' ailments, patient-reported outcomes (PRO) have become of key importance in modern cancer treatment. The implementation and first results of a systematic electronic real-time assessment of PRO in routine care is described. METHODS: Consecutive patients presenting for the first time to a German comprehensive cancer center were asked to fill in an adaptive self-administered electronic questionnaire consisting of standardized PRO measures. After completion, patient-reported data was linked to the patients' medical files for discussion in the first consultation with the treating physician. Interviews with staff were conducted to identify barriers in implementation. RESULTS: Out of 160 cancer patients, 126 (79 %; mean age 63 years, 67 % males) agreed to participate. The number of recruited patients increased over time. Of participating patients, 67 % provided complete information on all PRO-related scales. On average, 31 min (range 3-140) were required to fill in the questionnaire. Of participating patients, 53.0 % comprised need for psychooncological support and 62 % revealed moderate to severe psychosocial distress. The mean score for global quality of life according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was 55.2 (SD +/-25.6). CONCLUSIONS: Comprehensive oncological treatment needs to consider disease symptoms, quality of life, preferences, and comorbidities of individual patients in a structured, standardized, and transparent way. Our findings indicate that an adaptive, self-administered electronic assessment tool for cancer patients to report a broad set of PRO can be feasibly implemented and is well accepted by patients in a realistic setting. PMID- 26887587 TI - A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease. AB - PURPOSE: Anxiety is a major component of breathlessness and is often palliated with benzodiazepines. Midazolam is a short-acting water-soluble benzodiazepine with a rapid onset of action and short half-life. Intranasal midazolam had been shown to be of marked clinical benefit in an uncontrolled pilot study for the control of dyspnoea. A blinded randomised controlled study was therefore undertaken across four Australasian palliative care services. METHODS: All participants received six numbered study nasal spray (SNS) bottles, three of which contained midazolam and three placebo. They were instructed to use one SNS bottle on each day they were breathless, for 6 days within 2 weeks. Dyspnoea scores were recorded before and at set time intervals following the first use of each SNS bottle. RESULTS: Across all SNS bottles, the maximum change of 2.1 on an 11-point numerical rating scale was seen at 60 min. There was no difference in dyspnoea score between the two arms. Approximately 50 % of participants in each arm had a positive response (i.e. >=2 point change in dyspnoea score from baseline). Anxiety scores at baseline were low. The most common adverse event was local nasal reactions. CONCLUSION: Intranasal midazolam had no clinical benefit over intranasal placebo for the control of dyspnoea. The low level of anxiety at baseline and dose of active drug delivered may have been important factors. Many participants found the SNS bottles to be a challenging mode of drug delivery. This study confirms the importance of placebo-controlled trials for defining best clinical practise. PMID- 26887588 TI - Psychological distress, health, and socio-economic factors in caregivers of terminally ill patients: a nationwide population-based cohort study. AB - PURPOSE: At some point in life, most people become caregivers to a terminally ill relative. Previous studies have shown that many caregivers experience psychological distress and declining physical health, but these studies have predominantly been conducted in specialized palliative care settings. Therefore, caregiver studies with a population-based approach are needed. We aimed to describe socio-economic characteristics, situational factors, pre-loss grief symptoms, depressive symptoms, caregiver burden, and health status in a general population of caregivers to terminally ill patients. METHOD: We conducted a nationwide population-based cohort study. Caregivers were systematically recruited through patients registered with drug reimbursement for terminal illness in 2012. Data on socio-economic characteristics was mainly obtained from Danish registries, whereas data on situational factors, distress, and health was measured in questionnaires. RESULTS: Of patients to responding caregivers (n = 3635), 89 % suffered from cancer, predominantly lung cancer (23 %). Of responding caregivers, 62 % were partners and 29 % were adult children. In total, one third of caregivers reported severe outcome, 15 % reported severe pre-loss grief symptoms, 16.1 % had moderate to severe depressive symptoms, and 12 % experienced high caregiver burden. Partners had the highest levels of pre-loss grief and depressive symptoms, while adult children reported the highest levels of caregiver burden. CONCLUSIONS: From this cohort, which was estimated to be representative of caregivers to terminally ill relatives in the general population, we found high levels of pre-loss grief, depressive symptoms, and/or caregiver burden in one third of all caregivers. These findings call for increased focus on caregivers' need of support. PMID- 26887589 TI - Phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the nucleus accumbens. AB - RATIONALE: Phentermine is structurally similar to methamphetamine and is widely used as an anti-obesity drug in the USA and many other countries. The potential for reward of phentermine has been noted; however, the mechanisms of phentermine dependence have not been established. OBJECTIVES: Here, we investigated the rewarding and dopaminergic behavioral responses to phentermine in mice and found that phentermine produced conditioned rewarding effects through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in the nucleus accumbens (NAc). METHODS: The impact of phentermine was assessed using conditioned place preference (CPP) test, climbing behavior test, and western blot analysis. RESULTS: Phentermine 1 and 3 mg/kg (i.p.) significantly increased CPP. Phentermine, a known dopamine releaser, boosted apomorphine-induced climbing behavior in mice, and methamphetamine (i.p.) also increased apomorphine-induced dopaminergic behavior. Phentermine and methamphetamine increased the level of expression of the dopamine transporter (DAT) and phospho-Akt proteins to a similar degree in the NAc of CPP mice. To determine whether the conditioned rewarding effects of phentermine were mediated through the PI3K/Akt pathway, we assessed the effects of the Akt inhibitor LY294002 on phentermine-induced place preference and climbing behavior. LY294002 (1 and 3 MUg/site, i.c.v.) reduced phentermine-induced CPP and phentermine-increased climbing behavior. However, LY294002 did not change CPP and climbing behavior itself and also did not decrease apomorphine-induced climbing behavior in mice. Further, LY294002 decreased the phentermine-increased levels of DAT protein and phosphorylation of Akt in the NAc of CPP mice. CONCLUSIONS: Thus, these findings suggest that phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the NAc. PMID- 26887591 TI - Endoscopic incision for the treatment of refractory esophageal anastomotic strictures: outcomes of 13 cases with a minimum follow-up of 12 months. AB - BACKGROUND AND AIM: Endoscopic incision is an alternative method for refractory esophageal strictures; however, little is known about its long-term efficacy. The aim of the study is to assess the long-term outcomes of endoscopic incision for treating refractory esophageal anastomotic strictures. METHODS: Between September 2011 and September 2014, 13 patients with refractory esophageal anastomotic strictures were treated with endoscopic incision. Their clinical data were retrospectively collected to evaluate the efficacy and safety of the technique. RESULTS: All the 13 patients underwent the procedure successfully with median operation duration of 15 minutes. A total of 27 sessions were necessary to maintain lumen patency until September 2015, and 7 patients needed retreatment. The symptoms relieved in all the cases, and the median dysphagia score decreased from 4 to 1 during a median follow-up of 25 months. The median diameter of stricture was enlarged from 4 mm to 12 mm. As a short-term effect, dysphagia symptoms improved in 100% (13/13), 84.6% (11/13) and 76.9% (10/13) of the patients one, three and six months after a single treatment. As long-term effect, the dysphagia improved in 61.5% (8/13), 63.6% (7/11) and 60% (6/10) of the patients 12, 18 and 24 months after a single treatment. CONCLUSIONS: The efficacy of endoscopic incision is favorable in the short term. However, retreatment is needed to maintain the long-term lumen patency for parts of the patients. PMID- 26887590 TI - The Minnesota living with heart failure questionnaire: comparison of different factor structures. AB - BACKGROUND: The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is one of the most widely used health-related quality of life questionnaires for patients with heart failure (HF). It provides scores for two dimensions, physical and emotional, and a total score. However, there are some concerns about its factor structure and alternatives have been proposed, some including a third factor representing a social dimension. The objectives of the present study were to analyze the internal structure of the MLHFQ and the unidimensionality of the total score, and to compare the different factor structures proposed. METHODS: The MLHFQ was given to 2565 patients with HF. The structural validity of the questionnaire was assessed by confirmatory factor analysis (CFA), and Rasch analysis. These two approaches were also applied to the alternative structures proposed. RESULTS: The CFA results for the hypothesized model of two latent factors and the Rasch analysis confirmed the adequacy of the physical and emotional scales. Rasch analysis for the total score showed only two problematic items. The results of the CFA for other two-factor structures proposed were not better than the results for the original structure. The Rasch analyses applied to the different social factors yielded the best results for Munyombwe's social dimension, composed of six items. CONCLUSIONS: Our results support the validity of using the MLHFQ physical, emotional and total scores in patients with HF, for clinical practice and research. In addition, they confirmed the existence of a third factor, and we recommend the use of Munyombwe's social factor. PMID- 26887592 TI - Accurate prediction of cellular co-translational folding indicates proteins can switch from post- to co-translational folding. AB - The rates at which domains fold and codons are translated are important factors in determining whether a nascent protein will co-translationally fold and function or misfold and malfunction. Here we develop a chemical kinetic model that calculates a protein domain's co-translational folding curve during synthesis using only the domain's bulk folding and unfolding rates and codon translation rates. We show that this model accurately predicts the course of co translational folding measured in vivo for four different protein molecules. We then make predictions for a number of different proteins in yeast and find that synonymous codon substitutions, which change translation-elongation rates, can switch some protein domains from folding post-translationally to folding co translationally--a result consistent with previous experimental studies. Our approach explains essential features of co-translational folding curves and predicts how varying the translation rate at different codon positions along a transcript's coding sequence affects this self-assembly process. PMID- 26887593 TI - Cytotoxicity considerations and electrically tunable release of dexamethasone from polypyrrole for the treatment of back-of-the-eye conditions. AB - Age-related macular degeneration (AMD) and diabetic macular edema (DME) are common causes of blindness in people aged over 55 years. Current treatment involves frequent intravitreal administration of corticosteroids such as dexamethasone. The aim of this research was to formulate an electrically controlled delivery system for dexamethasone. Polypyrrole (PPy) was polymerized with dexamethasone sodium phosphate (Dex-P) through two approaches. Firstly, conventional films (CFs) of PPy were electropolymerized by applying a constant current density of 2 mA/cm2 for 4 min. Secondly, for the first time, we report drug-loaded ethanol-washed films (EWFs). EWFs were prepared in the same manner as CFs, except ethanol washing steps were introduced in the middle and at the end of PPy electropolymerization. The ethanol washing removed unbound PPy oligomers resulting in the formation of smooth surfaces with two distinct layers when viewed in cross-section. The EWFs showed superior electrochemical activity compared to CFs. Sustained release was observed from both CFs and EWFs with bursts of release triggered by electrical stimulation. The EWFs were initially more responsive to the electrical trigger, offering future opportunities to fine tune release. The cytotoxicity of aqueous extracts collected from both films was evaluated on human adult retinal pigment epithelium (ARPE-19) cells using a 3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with negligible toxicity observed. The results suggest PPy-Dex-P films are highly suitable for the development of electro-responsive implants for the treatment of AMD and DME. PMID- 26887596 TI - Editor's Notes--February 2016. PMID- 26887597 TI - Growth, Maturation, and Exercise During Youth. PMID- 26887595 TI - A generic selection system for improved expression and thermostability of G protein-coupled receptors by directed evolution. AB - Structural and biophysical studies as well as drug screening approaches on G protein-coupled receptors (GPCRs) have been largely hampered by the poor biophysical properties and low expression yields of this largest class of integral membrane proteins. Thermostabilisation of GPCRs by introduction of stabilising mutations has been a key factor to overcome these limitations. However, labelled ligands with sufficient affinity, which are required for selective binding to the correctly folded receptor, are often not available. Here we describe a novel procedure to improve receptor expression and stability in a generic way, independent of specific ligands, by means of directed evolution in E. coli. We have engineered a homogenous fluorescent reporter assay that only detects receptors which are correctly integrated into the inner cell membrane and, thus, discriminates functional from non-functional receptor species. When we combined this method with a directed evolution procedure we obtained highly expressing mutants of the neurotensin receptor 1 with greatly improved thermostability. By this procedure receptors with poor expression and/or low stability, for which no ligands or only ones with poor binding properties are available, can now be generated in quantities allowing detailed structural and biophysical analysis. PMID- 26887598 TI - Aerobic Fitness and Training in Children and Adolescents. PMID- 26887594 TI - Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs. AB - Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitantly a decreased expression of CSC-associated genes, and reduced cellular mobility and sphere formation. Investigating basic cellular metabolic responses, we detected lower oxygen consumption and glucose uptake, while intracellular ROS levels increased. This was effectively neutralized by the addition of antioxidants, indicating an essential role of the cellular redox balance. Further analysis on energy metabolism related signaling revealed that meisoindigo inhibited LKB1, but activated AMPK. Both of them were involved in cellular apoptosis. Additional in situ hybridization in tissue sections of PDAC patients reproducibly demonstrated co-expression and -localization of LKB1 and CD133 in malignant areas. Finally, we detected that CD133+/CD44+ were more vulnerable to meisoindigo, which could be mimicked by LKB1 siRNAs. Our results provide the first evidence, to our knowledge, that LKB1 sustains the CSC population in PDACs and demonstrate a clear benefit of meisoindigo in treatment of gemcitabine-resistant cells. This novel mechanism may provide a promising new treatment option for PDAC. PMID- 26887600 TI - Elite Youth Sports. PMID- 26887599 TI - Muscle Strength and Resistance Training in Youth--Do They Affect Cardiovascular Health? PMID- 26887601 TI - Physical Activity, Inactivity, and Health During Youth. PMID- 26887602 TI - Exercise and Cognition. PMID- 26887603 TI - Psychosocial Aspects of Youth Physical Activity. PMID- 26887604 TI - Metabolism and Exercise During Youth. PMID- 26887605 TI - Endocrinology and Pediatric Exercise Science. PMID- 26887606 TI - Neuromuscular Physiology and Youth. PMID- 26887607 TI - Cardiovascular Physiology and Disease in Youth. PMID- 26887608 TI - Childhood Obesity, Physical Activity, and Exercise. PMID- 26887609 TI - Chronic Diseases, Exercise, and Physical Activity in Childhood: 2015 in Review. PMID- 26887610 TI - Erratum: Weiss et al. 2015. AB - Physical and Psychosocial Health Outcomes," in Ped Exerc Sci, 27(4), pp. 546-558, http://dx.doi.org/10.1123/pes.2015-0011, Kipp's affiliation was incorrectly listed as the Dept. of Kinesiology and Health Promotion, Lexington, KY. Kipp's correct affiliation is with the Dept. of Health and Human Performance, Texas State University, San Marcos, TX. We apologize for this error. PMID- 26887612 TI - Alzheimer's disease and diet: a systematic review. AB - : Purpose/Aim: Approximately 44 million people worldwide have Alzheimer's disease (AD). Numerous claims have been made regarding the influence of diet on AD development. The aims of this systematic review were to summarize the evidence considering diet as a protective or risk factor for AD, identify methodological challenges and limitations, and provide future research directions. METHODS: Medline, PsycINFO and PsycARTICLES were searched for articles that examined the relationship between diet and AD. RESULTS: On the basis of the inclusion and exclusion criteria, 64 studies were included, generating a total of 141 dietary patterns or "models". All studies were published between 1997 and 2015, with a total of 132 491 participants. Twelve studies examined the relationship between a Mediterranean (MeDi) diet and AD development, 10 of which revealed a significant association. Findings were inconsistent with respect to sample size, AD diagnosis and food measures. Further, the majority of studies (81.3%) included samples with mean baseline ages that were at risk for AD based on age (>65 years), ranging from 52.0 to 85.4 years. The range of follow-up periods was 1.5-32.0 years. CONCLUSIONS: The mean age of the samples poses a limitation in determining the influence of diet on AD; given that AD has a long prodromal phase prior to the manifestation of symptoms and decline. Further studies are necessary to determine whether diet is a risk or protective factor for AD, foster translation of research into clinical practice and elucidate dietary recommendations. Despite the methodological limitations, the finding that 50 of the 64 reviewed studies revealed an association between diet and AD incidence offers promising implications for diet as a modifiable risk factor for AD. PMID- 26887611 TI - Comparison of ILK and ERP29 expressions in benign and malignant pancreatic lesions and their clinicopathological significances in pancreatic ductal adenocarcinomas. AB - INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor of the pancreas with poor prognosis. The lack of understanding of the molecular mechanisms of PDAC and biomarkers for early diagnosis might be two of the reasons for the poor prognosis of PDAC. MATERIALS AND METHODS: ILK and ERP29 protein expressions in PDAC, peritumoral tissues, benign pancreatic lesions, and normal pancreatic tissues were measured by immunohistochemistry and the clinical and pathological significances of ILK and ERP29 in PDAC were analyzed. RESULTS: The percentages of positive ILK and negative ERP29 expressions were significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01). Benign pancreatic lesions with positive ILK and negative ERP29 expressions exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive ILK and negative ERP29 expressions was significantly lower in PDAC patients without lymph node metastasis and invasion, and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P < 0.05 or P < 0.01). Kaplan-Meier survival analysis showed that positive ILK and negative ERP29 expressions were significantly associated with survival in PDAC patients (P < 0.001). Cox multivariate analysis revealed that positive ILK and negative ERP29 expressions were independent poor prognosis factors in PDAC patients. CONCLUSIONS: Positive ILK and negative ERP29 expressions are associated with the progression of PDAC and poor prognosis in patients with PDAC. PMID- 26887614 TI - [Hormonal therapy for hormone receptor-positive metastatic breast cancer]. PMID- 26887615 TI - [Sensitivity of esophageal squamous cell carcinoma cells to rapamycin can be improved by siRNA-interfered expression of p70S6K]. AB - OBJECTIVE: To explore the differences in sensitivity to rapamycin of five esophageal squamous cell carcinoma cell lines with different differentiation and the changes of sensitivity of the cells after siRNA-interfered expression of p70S6K. METHODS: Effects of rapamycin on proliferation of ESCC cell lines with different differentiation, EC9706, TE-1, Eca109, KYSE790 and KYSE450 cells, were investigated using cell counting kit 8 (CCK-8) assay, and according to the above results, the EC9706 cells non-sensitive to rapamycin were chosen to be transfected with p70S6K-siRNA. The changes in sensitivity of cells to rapamycin were measured in vitro and in vivo using CCK-8 kit, flow cytometry and tumor formation in nude mice. RESULTS: CCK-8 results showed that all the five cell line cells were sensitive to low concentration of rapamycin (<100 nmol/L), but TE-1 and EC9706 cells, which were with poor differentiation, showed resistance to high concentration of rapamycin. After EC9706 cells were treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and p70S6K-siRNA, the proliferation rates of EC9706 cells were (48.67 +/- 1.68)%, (15.45 +/- 1.54)%, (14.00 +/- 0.91)%, (10.97 +/- 0.72)% and (2.70 +/- 0.32)%, respectively, and were significantly lower than that of cells treated with 50, 100, 200, 500 and 1 000 nmol/L rapamycin and control siRNA [(74.53 +/- 1.71)%, (68.27 +/- 1.35)%, (71.74 +/- 2.44)%, (76.23 +/ 1.02)% and (80.21 +/- 2.77)%] (P<0.05 for all). The results of flow cytometry showed that the ratios of cells in G1 phase of the p70S6K-siRNA, rapamycin and p70S6K-siRNA+ rapamycin groups were (53.82 +/- 1.78)%, (57.87 +/- 4.01)% and (73.73 +/- 3.68)%, respectively, significantly higher than that in the control group (46.09 +/- 2.31)% (P<0.05 for all). The results of tumor formation test in vivo showed that the inhibitory effect of rapamycin on tumor growth was stronger after the cells were transfected with p70S6K-siRNA, and the inhibition rate was 96.5%. CONCLUSION: ESCC cells with different differentiation have different sensitivity to rapamycin, and p70S6K-siRNA can improve the sensitivity of cells to rapamycin in vitro and in vivo. PMID- 26887613 TI - Dysfunction of Wntless triggers the retrograde Golgi-to-ER transport of Wingless and induces ER stress. AB - Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of function or porcupine (porc) depletion, and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg, and elucidates a correlation between Wnt secretion and ER stress during development. PMID- 26887616 TI - [The Hsp90 inhibitor FW-04-806 suppresses Bcr/Abl-mediated growth of leukemia cells by inhibiting proliferation and inducing apoptosis]. AB - OBJECTIVE: To investigate the antitumor efficacy and mechanism of HSP90 inhibitor FW-04-806 against Bcr/Abl(+) leukemia K562 and HL60 cells and their mechanisms of action. METHODS: MTT assay was used to assess the proliferation-inhibiting effect of FW-04-806. Cell cycle was analyzed with propidium iodide by flow cytometry. Cell apoptosis was determined using the FITC mV apoptosis detection kit. Western blot was applied to reveal the protein expression of related proliferative and apoptotic signaling pathways. The changes of mitochondrial membrane potential were detected by flow cytometry. Protein-protein interactions was shown by co immunoprecipitation. The level of mRNA was assessed by real-time RT-PCR. RESULTS: FW-04-806 obviously inhibited cell proliferation in the HL60, K562 and HL60/Bcr Abl cell lines, with an IC50 of (30.89 +/- 0.12) umol/L, (9.76 +/- 0.19) umol/L and (8.03 +/- 0.26) umol/L, respectively (P<0.001). Compared with the vehicle group, the two increasing doses of FW-04-806 showed inhibition of tumor growth at a rate of (17.40 +/- 0.34)% and (34.33 +/- 5.00)%, respectively, in the K562 cell line groups (P=0.003), and (18.90 +/- 1.45)% and (35.60 +/- 3.55)% (P=0.001) in the HL60/Bcr-Abl cell line groups. FW-04-806 dissociated Hsp90/Cdc37 chaperon/co chaperon complex, followed by degradation of the Hsp90 proteins through proteasome pathway without affecting mRNA expression. FW-04-806 induced apoptosis and led to G2/M arrest. CONCLUSION: Our findings indicate that FW-04-806 displays potential antitumor effect by suppressing the proliferation and apoptosis in Bcr/Abl(+) leukemia cells in vivo. PMID- 26887617 TI - [Lymph node metastasis patterns and influencing factors in patients with limited esophageal small cell carcinoma]. AB - OBJECTIVE: To explore the patterns and influencing factors of lymph node metastasis in limited esophageal small cell carcinoma (PESCC). METHODS: A total of 98 limited stage PESCC patients who underwent surgery were selected for this study. The lymph node metastasis ratio at different sites, depth of invasion, tumor length and other factors were analyzed to assess their influence on lymph node metastasis. RESULTS: Among the 98 PESCC cases, 46 cases had lymph node metastasis (46.9%). 100 out of 833 lymph nodes had metastasis, with a metastasis ratio of 12.0%. For upper thoracic esophageal small cell carcinomas, lymph node metastasis ratios were 42.9%, 12.5%, 0 and 0 in the superior mediastinum, middle mediastinum, inferior mediastinum and abdominal cavity, respectively. In the middle thoracic PESCCs, the lymph node metastasis ratios were 18.8%, 7.7%, 15.7%, and 15.3%, respectively. In the lower thoracic PESCCs, the lymph node metastasis ratios were 0, 0, 27.3% and 23.5%, respectively. Lymph node metastasis rates in PESCCs at stages T1, T2, T3, T4 were 15.4%, 42.3%, 63.9%, and 80.0%, respectively. The lymph node metastasis ratios in PESCCs at stages T1, T2, T3, T4 were 2.0%, 8.3%, 17.8% and 25.0%, respectively. Lymph node metastasis rate and lymph node metastasis ratio at different T stages were of significant difference (P<0.05 for all). Lymph node metastasis rates in patients with tumor <3 cm, 3-5 cm, and >5 cm were 30.6%, 46.9% and 66.7%, respectively, and lymph node metastasis ratios were 5.4%, 11.0% and 21.1%, respectively. Lymph node metastasis rate and lymph node metastasis ratio in patients with different tumor length had significant differences (P<0.05 for all). Lymph node metastasis ratio was 11.6% in the Chr-A negative and weak positive group, much higher than 4.3% in the Chr-A positive group (P=0.013). There was a tendency that lymph node metastasis ratio of NSE-positive group was higher than that of NSE-negative and weak positive group (P=0.069). The logistic univariate analysis did not find high risk factors of distant lymph node metastasis (all P>0.05). Logistic multivariate analysis found that only depth of invasion was a risk factor of lymph node metastasis in limited PESCC (P=0.002). CONCLUSIONS: Esophagus small cell carcinomas sometimes have early lymph node metastases in many sites and distant range. The middle thoracic PESCCs tend to have extensive metastasis quite common in the upper mediastinal lymph nodes. Lower mediastinal and abdominal lymph node metastases are often seen in lower thoracic PESCCs. The depth of invasion and tumor length are main factors influencing mediastinal lymph node metastasis. The depth of invasion is an independent risk factor for lymph node metastasis. PMID- 26887618 TI - [Evaluation of the blood flow in common hepatic tumors by multi-slice spiral CT whole-liver perfusion imaging]. AB - OBJECTIVE: To study the characteristics of blood flow in common hepatic tumors by 256-slice spiral CT whole-liver perfusion imaging. METHODS: Seventy-one patients with hepatic tumors were examined retrospectively by 256-slice spiral CT whole liver perfusion. Among them, twenty-seven cases were of primary hepatic cancer, twenty-four cases of hepatic hemangioma, and twenty cases of hepatic metastases.Regions of interest (ROIs) were placed in the tumor parenchyma (Area A), peritumoral hepatic parenchyma (Area B), and normal hepatic parenchyma (Area C), respectively. The time density curves (TDC) were drawn, and perfusion parameters including hepatic arterial perfusion(HAP), portal venous perfusion(PVP), total liver perfusion(TLP) and hepatic erfusion index(HPI) were obtained. The values of ROIs were measured, and the perfusion parameters in the areas A, B, C of different hepatic tumors were statistically analyzed. RESULTS: The values of HAP, PVP, HPI in the tumor parenchyma of primary hepatic carcinoma were (20.00 +/- 11.41)ml . min(-1) . 100 ml(-1,) (32.31 +/- 21.06)ml . min(-1) . 100 ml(-1,) (52.31 +/- 30.55)ml . min(-1) . 100 ml(-1,) and (39.67 +/- 11.19)%, showing significant difference as compared with those in peritumoral hepatic parenchyma and in normal hepatic parenchyma(P<0.05). The values of HAP, TLP, and HPI in the tumor parenchyma of hepatic hemangioma were (40.39 +/- 29.23)ml . min( 1) . 100 ml(-1,) (132.72 +/- 132.65) ml . min(-1) . 100 ml(-1,) and (35.51 +/- 15.12)%, were significantly different as compared with those in the peritumoral hepatic parenchyma and in normal hepatic parenchyma(P<0.05). The values of HAP, PVP, HPI in the tumor parenchyma of hepatic metastases were (17.43 +/- 12.27)ml . min(-1) . 100 ml(-1,) (36.19 +/- 34.99) ml . min(-1) . 100 ml(-1,) and (37.86 +/- 14.49)%, significantly different as compared normal hepatic parenchyma (P<0.05). The HAP, PVP, and TLP of tumor tissue and the PVP and HPI of peritumoral tissue in different hepatic tumors were statistically significantly different (P<0.05). CONCLUSIONS: The multi-slice spiral CT whole-liver perfusion has certain value in the diagnosis of common hepatic tumors. Perfusion parameters in different areas of common hepatic tumors have their own hemodynamic characteristics. PMID- 26887619 TI - [Impact of microwave dealing with the cutting surface on the hepatocellular carcinoma recurrence after hepatectomy]. AB - OBJECTIVE: To explore the impact of microwave dealing with cutting surface on perioperative liver function recovery and recurrence and metastasis after hepatectomy for HCC. METHODS: Clinical data of 133 patients with HCC from March 2009 to November 2010 were retrospectively analyzed. They were divided into the conventional surgery group (66 cases) and microwave treatment group (67 cases). A domestic ECO-100 microwave knife was inserted into the liver cutting surface 0.5 cm from the cutting edge, and repeated multi-point burning with an average time of 25 minutes in the microwave treatment group. Then the perioperative liver function recovery and recurrence and metastasis in the two groups were compared. RESULTS: The operation time of conventional surgery group was (158.0 +/- 31.0) minutes, and that of microwave treatment group was significantly longer (181.0 +/ 28.0) minutes (P=0.027). There were no significant differences in the liver function recovery between the two groups (P>0.05). There were 6 cases of recurrence and metastasis after 6 months and 9 cases after 12 months in the microwave treatment group, while there were 15 cases of recurrence and metastasis after 6 months and 20 cases after 12 months in the conventional surgery group, showing a significant difference (P=0.034 and 0.022, respectively). CONCLUSIONS: Microwave dealing with the cutting surface has no significant effect on perioperative liver function recovery in hepatectomy. However, microwave treatment can reduce the in situ recurrence in HCC patients within the first year after surgery, indicating a good clinical application value. PMID- 26887621 TI - [Prognostic value of AJCC TNM Staging 7th edition in limited-stage small cell lung cancer: validation in 437 patients]. AB - OBJECTIVE: To explore the impact of AJCC TNM Staging 7th edition on survival outcome of limited stage small cell lung cancer (SCLC). METHODS: Four hundred and thirty-seven SCLC patients with completed diagnosis and treatment data treated in our department between January 1996 and December 2006 were reclassified according to the AJCC TNM Staging 7th edition. The patients of stages IA, IB, IIA, IIB, IIIA, IIIB were 8, 44, 7, 64, 192 cases, respectively. Kaplan-Meier method was used for survival analysis and log-rank test was used to identify the prognostic factors. The survival rate was determined using chi-square test. RESULTS: The median follow-up time was 64 months. The median survival time was 26.2 months and median progression free survival time was 13.7 months. The 1-, 2- and 5-year overall survival rates were 86.0%, 52.7%, and 29.7%, respectively. The log-rank test showed that TNM stage is a statistically significant prognostic factor for OS in LS-SCLC (P<0.001). TNM staging system generally allowed a good separation in pairwise comparison for OS between successive stages except there was no significant difference between stages I and II (P=0.061). The 5-year progression free survival rates of patients of stage I, II, IIIA and IIIB were 53.2%, 43.2%, 16.8%, and 10.9%, respectively. TNM stage also was a statistically significant prognostic factor for PFS in LS-SCLC (P<0.001), but there was no significant difference between successive stages (P>0.05 for all). The T staging confirmed significant influence on OS (P<0.001) with no significant difference between successive stages (P>0.05 for all), while T stage was not a significant prognostic factor for PFS in the LS-SCLC patients (P=0.194). N stage also had a significant influence on OS (P<0.001), but with no significant differences between successive stages except N1 and N2 (P=0.001). N staging also showed significant influence on PFS (P=0.001), but with no significant difference between successive stages (P>0.05) except that between the 5-year survival rates of N2 and N3 cases (P=0.013). The cumulative brain metastasis rates of stages I, II, IIIA, and stage IIIB were 17.3%, 28.6%, 33.3%, and 35.8%, respectively(P=0.072), and were 12.8% and 30.8% for pathological stage I and clinical stage I (P=0.203). CONCLUSION: AJCC TNM Staging 7th edition criteria for LS-SCLC patients have a high prognostic impact and therefore are preferable in clinical practice and future therapeutic trials. PMID- 26887620 TI - [Prognostic significance of clinical risk score system after resection of hepatic metastases from colorectal cancer]. AB - OBJECTIVE: To validate the prognostic significance of Clinical Risk Score (CRS) system proposed by Fong et al. after hepatectomy of liver metastasis from colorectal cancer. METHODS: The clinicopathological data were collected retrospectively from 294 patients with hepatic metastases from colorectal cancer who received liver resection between January 2000 and August 2014 in Peking University Cancer Hospital. Routine follow-up was done by outpatient interview or telephone. Statistical analysis was conducted to compare the survival of different CRS patients. RESULTS: After a median follow-up of 19 months (2-129 months) for all the 294 patients, the median overall survival and disease-free survival were 35 months and 11 months, respectively. The postoperative 1-, 3- and 5-year overall survival rates were 89.0%, 49.0%, and 35.7%, and the disease-free survival rates were 47.2%, 22.2%, and 18.2%, respectively. For the six different groups with CRS of 0, 1, 2, 3, 4, 5 accordingly, the median overall survival was 64, 59, 33, 35, 17 and 15 months, respectively, showing a significant difference (P=0.002), and the median disease-free survival was 16, 19, 13, 10, 4 and 6 months, respectively, showing also a significant difference (P<0.001). For patients whose CRS were 0-2 and 3-5, the median overall survival was 44 and 33 months, respectively, with a significant difference between them (P=0.022), and the median disease-free survival was 15 and 8 months, respectively, with also a significant difference (P<0.001). CONCLUSION: This CRS system may predict the prognosis for patients with hepatic metastasis from colorectal cancer after hepatectomy, therefore to provide useful reference for making treatment plan for those patients. PMID- 26887622 TI - [Prognostic analysis of benign, borderline and malignant phyllodes tumors of the breast]. AB - OBJECTIVE: To explore the prognosis of benign, borderline and malignant phyllodes tumors of the breast. METHODS: Data from 246 women with phyllodes tumors of the breast treated in the Cancer Hospital, Chinese Academy of Medical Sciences between January 2002 and December 2012, were collected and analyzed retrospectively. The patients were followed-up for a median of 48 months (range 1 138 months). Kaplan-Meier analysis and Cox proportional hazard model were used to analyze the factors affecting the disease-free survival. RESULTS: Among the 246 patients, 65 were dropped out from the follow-up. 56 patients had local recurrence, 5 patients had distant metastasis, while one case had both local recurrence and distant metastasis. The median disease-free survival time was 39 months. Kaplan-Meier survival analysis revealed that fibroadenoma history and type of primary surgery were associated to the disease-free survival of phyllodes tumors of the breast (P<0.001, P=0.043), while histological type and primary tumor size had no significant relationship with the disease-free survival (P=0.083, P=0.974). The multivariate Cox proportional hazard model showed that type of primary surgery, fibroadenoma history and histological types are all independent factors affecting the disease-free survival (P=0.009, P=0.001 and P<0.001). CONCLUSION: Phyllodes tumors of the breast have a relatively good prognosis on the whole. Type of primary surgery, fibroadenoma history and histological type are independent factors predicting the disease-free survival of patients with phyllodes tumors of the breast. PMID- 26887623 TI - [Effect of resection margin and tumor number on survival of patients with small liver cancer]. AB - OBJECTIVE: To explore the significance of resection margin and tumor number on survival of patients with small liver cancer after hepatectomy. METHODS: We collected 219 cases with small liver cancer undergoing hepatectomy in Cancer Hospital, Chinese Academy of Medical Sciences between December 2003 to July 2013. The survival rates were compared by log-rank test between two resection margin groups (>= 1 cm vs. <1 cm), different tumor number groups (single tumor vs. multiple tumors). We also performed a multifactor analysis by Cox model. RESULTS: The 1-, 3-, 5- and 10- year overall survival rates were 95.9%, 85.3%, 67.8% and 53.3%, respectively, in all patients. The median survival time was 28 months in the group of <1 cm resection margin and 36 months in the group of >= 1 cm resection margin (P=0.249). The median survival time was 36 months in the group of single tumor and 26 months in the group of multiple tumors (P=0.448). The multifactor analysis also did not show significant effect of resection margin and tumor number on the patients' survival. CONCLUSIONS: For small liver cancer, the resection margin of 1 cm might be advised. Increasing resection margin in further could probably not improve therapeutic effect. Standardized operation and combined treatment will decrease the negative influence of multiple tumors on overall survival. PMID- 26887624 TI - [Clinical application of ultrasound-guided radiofrequency ablation for primary hepatocellular carcinoma near the liver surface]. AB - OBJECTIVE: To explore the value of ultrasound-guided percutaneous radiofrequency ablation (RFA) in designing the indication, treatment protocol and operational skills for patients with primary hepatocellular carcinoma (HCC) near the liver surface. METHODS: Sixty-one HCC patients with 69 lesions, confirmed by clinical examination and pathology, underwent percutaneous radiofrequency ablation. The study included 40 cases of liver function Child-Pugh grade A and 21 cases of grade B. The average size of tumors was (3.8 +/- 1.2) cm, tumor diameter >= 4 cm accounted for 39.1% (27/69 lesions), and the average age was 58.2 years (range, 35-76 years). Taking comprehensive measures, such as intraperitoneal injection of saline adjacent to the tumor before RFA, increasing the puncture sites on the surface of tumor to avoid overlapping of the central portion of tumor, repeated ablation of the needle track to reduce needle tract metastasis, avoid vertical puncture, and other additional measures, to improve the inactivation of tumors adjacent to the liver surface. Enhanced CT/MRI was performed to evaluate the curative effect at 1, 3, 6 and 24 months after the treatment. RESULTS: The inactivation rate of tumor was 98.6% (68/69 lesions) and local recurrence rate was 5.8%(4/69) after RFA. The tumor-related marker AFP was 1 000-1 500 ng/ml before and reduced to (98.5 +/- 42.5) ng/ml after radiofrequency ablation, among them returned to normal in 13 cases (21.3%). Since the ablation area was rather small, the level of serum alanine aminotransferase was elevated only to (148.5 +/ 38.5) U/ml at one week after RFA and returned to normal at (1.8 +/- 0.6) week after RFA. No patient experienced severe liver dysfunction. The local HCC recurrent rate after RFA was 5.8%(4/69 lesions) and intrahepatic heterotopic recurrence rate was 24.6% (15/61). The 20-61 months follow-up showed that the 1-, 2- and 3-year survival rate was 83.6%, 57.3% and 44.2%, respectively. CONCLUSIONS: Ultrasound-guided percutaneous radiofrequency ablation provides an effective minimally invasive treatment for primary HCC near the liver surface. Taking some additional measures such as intraperitoneal injection of saline, increase of percutaneous puncture sites, and avoiding vertical needle puncture, may reduce complications and improve the therapeutic outcome. RFA is one of effective and minimally invasive treatment and causing less liver damage for primary HCC near the liver surface. PMID- 26887625 TI - [Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment]. AB - OBJECTIVE: To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment. METHODS: Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks. RESULTS: With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (<= 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post operative disease free survival (<= 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%). CONCLUSION: Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments. PMID- 26887626 TI - [Treatment of refractory pulmonary metastases from hepatocellular carcinoma by transcatheter arterial chemoembolization using arsenic trioxide in combination with sorafinib]. PMID- 26887627 TI - [Cost-effectiveness analysis of two breast cancer screening modalities in Shanghai, China]. AB - OBJECTIVE: To evaluate the cost-effectiveness of two breast cancer screening modalities conducted in Minhang district of Shanghai, China. METHODS: An organized and an opportunistic breast screening programs were implemented among women aged 35-74 years in Minhang district of Shanghai between May 2008 and Oct 2010, and were compared with the results obtained without screening. Costs related to screening were obtained by access to finance data of the screening programs, and costs of first treatment were collected through patient survey and medical reimbursement system query. Information on breast cancer stage was obtained from Shanghai Cancer Registry and confirmed by medical chart review. The effectiveness of screening was evaluated by breast cancer stage improvement.Cost effectiveness ratios (CERs) were computed as costs of gaining a stage improvement from a specified screening strategy when compared with the results obtained without screening. Incremental cost-effectiveness (ICER) which compares the two screening strategies was calculated by dividing the difference in total net costs and the difference in stages improved between the two screening strategies. RESULTS: Thirty-five, one hundred and ninety-three and four hundred and seventy nine breast cancer cases were identified in the organized screening, opportunistic screening and control groups, with an early detection rate of 46.9%, 40.7% and 38.9%, respectively. The costs of screening were 208 yuan per person or 72 453 yuan per case detected in the organized screening group and were 21 yuan per person or 11 640 yuan per case detected in the opportunistic screening group. The total cost was 103 650 yuan per case in the organized screening group, significantly higher than 50 712 yuan in the opportunistic screening group and 35 413 yuan in the control group. However, the average direct medical cost was significantly lower in the organized screening group than that in the opportunistic screening group and control group, with median costs of 11 024 yuan, 13 465 yuan and 14 243 yuan per case, respectively (P<0.001). The additional cost per case detected was 68 237 yuan for the organized screening and 15 299 yuan for opportunistic screening. The CERs were 135 291 yuan and 152 179 yuan per stage improved in the organized screening and opportunistic screening relative to the control group, with ICER of organized versus opportunistic screening being 131 086 yuan per stage improved. CONCLUSIONS: The organized screening modality and the opportunistic one are both effective in early detecting breast cancer in Chinese women. The organized screening costs more than opportunistic screening, but with a better cost-effectiveness. It may be used as an option in economically developed areas of China. PMID- 26887629 TI - Ultrafast deactivation of bilirubin: dark intermediates and two-photon isomerization. AB - Bilirubin is a neurotoxic product responsible for neonatal jaundice, which is generally treated by phototherapy. The photoreaction involves ultrafast internal conversion via an elusive intermediate and Z-E isomerization with minor yield (less than 3% in solution). The structure of the intermediate remains unclear. Here, the combination of UV-vis and mid-IR ultrafast transient absorption spectroscopy reports a comprehensive picture of the mechanism and provides essential structural information about the intermediate species. Thus, spectral dynamics during the earliest ps unveils a wavepacket travelling from the Franck Condon region to the crossing point with a dark state. The latter shows a tighter molecular skeleton than the ground state and decays with 15 ps time constant. Remarkably, the relative contribution of a non-decaying component increases linearly with pump energy, suggesting that Z-E isomerization could also be triggered by two-photon excitation. Implications for the photochemistry of protein-bound open tetrapyrroles are discussed. PMID- 26887628 TI - Thrombopoietic status of patients on haemodialysis. AB - Thrombocytopenia is a potential dialysis-related treatment complication. Developments in bio-compatible dialyser membranes have decreased the occurrence of thrombocytopenia. We investigated whether thrombopoiesis is impaired in haemodialysis patients by measuring the thrombopoietin level and absolute immature platelet number (AIPN) in the blood of patients undergoing haemodialysis. Samples were collected from the dialysis tubing pre- and post- haemodialysis in a cohort of 45 well-characterized haemodialysis patients. Thrombopoietin levels and AIPN increased following haemodialysis, despite no change in platelet count. Observed increase in release of immature platelets from the bone marrow following haemodialysis indicates possible complement activation secondary to interaction between blood constituents and the dialysis membrane. PMID- 26887630 TI - Substantiating the need for primary care-based sexual health promotion interventions for ethnic minority adolescent women experiencing health disparities. AB - PURPOSE: Assess the context of psychological distress, violence, and substance use among African- and Mexican-American adolescent women with a history of STI, violence, or high sexual risk behavior. These adolescents experience multiple health disparities, limited access to care, and are at particularly high risk of adverse sexual health outcomes. The results will inform sexual health promotion interventions provided by advanced practice nurses in primary care-based settings for women experiencing these disparities. METHODS: Analysis of self-report data obtained at study entry from African- and Mexican-American adolescent women (n = 559) enrolled in a randomized trial of a behavioral intervention for sexual risk reduction. CONCLUSIONS: High levels of psychological distress, sexual risk behavior, sexually transmitted infection (STI), personal and friend/peer substance use, alcohol use, and violence were reported by women at study entry. Analyses found that STI, physical violence, and substance-using friends were twice as likely associated with personal substance use. Alcohol users were five times more likely to use other substances. Mexican Americans were three times more likely than African Americans to use substances. IMPLICATIONS FOR PRACTICE: Recommendation is made for integration of multicomponent sexual health promotion interventions as advanced practice nurse provider services addressing these health disparities within primary care-based settings. PMID- 26887631 TI - Review of Interventions to Enhance the Health Communication of People With Intellectual Disabilities: A Communicative Health Literacy Perspective. AB - BACKGROUND: Communicative health literacy is a term relating to the range of competencies and capabilities patients bring to the task of seeking information about their health and sharing it with others. This exchange can be problematic for people with intellectual disabilities. The aim of this review was to synthesize findings from interventions designed to improve health communication for people with intellectual disabilities. MATERIALS AND METHOD: Available evidence was systematically reviewed, and findings from 14 articles were synthesized in a narrative review. RESULTS AND CONCLUSIONS: Interventions addressed communicative aspects of health consultations, taking into account emotional factors and social context. Questions remain about how such interventions might impact on real-life health consultations and how issues of power might be resolved. PMID- 26887632 TI - Local and interannual variations in mercury and cadmium in eggs of eight seabird species of the Sinaloa coast, Mexico. AB - Mercury (Hg) and cadmium (Cd) concentrations in eggs of 8 seabird species inhabiting 5 coastal ecosystems in Sinaloa, Mexico were determined during 2 breeding seasons (2012 and 2013): blue-footed booby (Sula nebouxii), brown booby (Sula leucogaster), double-crested cormorant (Phalacrocorax auritus), magnificent frigatebird (Fregata magnificens), brown pelican (Pelecanus occidentalis), royal tern (Thalasseus maximus), laughing gull (Leucophaeus atricilla), and Heermann's gull (Larus heermanni). The interspecific differences found in the concentrations of both metals were attributed to the diet and foraging ecology of the species. The highest Hg concentrations were detected in piscivorous species (brown pelican, 0.42 ug/g; brown booby, 0.31 ug/g; blue-footed booby, 0.26 ug/g; and double-crested cormorant, 0.23 ug/g); whereas species with more varied diets presented the highest Cd concentrations (Heermann's gull, 0.31 ug/g; laughing gull, 0.27 ug/g; and magnificent frigatebird, 0.27 ug/g). Cadmium concentrations were significantly greater in 2013 than 2012 for most species, and brown pelican and laughing gull also had higher Hg concentrations in 2013 in Santa Maria Bay, suggesting a relationship as a result of the changes either in oceanographic conditions or in continental runoff. Mercury concentrations in brown pelican and Cd concentrations in Heermann's gull and laughing gull were above threshold levels for adverse effects on reproduction and survival. Environ Toxicol Chem 2016;35:2330-2338. (c) 2016 SETAC. PMID- 26887633 TI - Easily accessible polymer additives for tuning the crystal-growth of perovskite thin-films for highly efficient solar cells. AB - For perovskite solar cells (Pero-SCs), one of the key issues with respect to the power conversion efficiency (PCE) is the morphology control of the perovskite thin-films. In this study, an easily-accessible additive polyethylenimine (PEI) is utilized to tune the morphology of CH3NH3PbI3-xClx. With addition of 1.00 wt% of PEI, the smoothness and crystallinity of the perovskite were greatly improved, which were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). A summit PCE of 14.07% was achieved for the p-i-n type Pero SC, indicating a 26% increase compared to those of the devices without the additive. Both photoluminescence (PL) and alternating current impedance spectroscopy (ACIS) analyses confirm the efficiency results after the addition of PEI. This study provides a low-cost polymer additive candidate for tuning the morphology of perovskite thin-films, and might be a new clue for the mass production of Pero-SCs. PMID- 26887635 TI - Decoupling Charge Transfer and Transport at Polymeric Hole Transport Layer in Perovskite Solar Cells. AB - Tailoring charge extraction interfaces in perovskite solar cells (PeSCs) critically determines the photovoltaic performance of PeSCs. Here, we investigated the decoupling of two major determinants of the efficient charge extraction, the charge transport and interfacial charge transfer properties at hole transport layers (HTLs). A simple physical tuning of a representative polymeric HTL, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate), provided a wide range of charge conductivities from 10(-4) to 10(3) S cm(-1) without significant modulations in their energy levels, thereby enabling the decoupling of charge transport and transfer properties at HTLs. The transient photovoltaic response measurement revealed that the facilitation of hole transport through the highly conductive HTL promoted the elongation of charge carrier lifetimes within the PeSCs up to 3 times, leading to enhanced photocurrent extraction and finally 25% higher power conversion efficiency. PMID- 26887637 TI - Seasonal and spatial ontogenetic movements of Gerreidae in a Brazilian tropical estuarine ecocline and its application for nursery habitat conservation. AB - The density and biomass of different ontogenetic phases (juvenile, sub-adult and adult) of the two most important sympatric Gerreidae species in the Goiana Estuary, north-east Brazil, are described in order to determine the patterns of estuarine habitat use and to identify nursery grounds. Eugerres brasilianus and Eucinostomus melanopterus were the most abundant gerreids in the main channel and adjacent estuarine beach habitats. Eugerres brasilianus is abundant in the main channel, whereas E. melanopterus is most common in the beach habitats. Significant interaction in density and biomass of juvenile and sub-adult size classes of E. brasilianus was found between season and area. In addition, E. brasilianus adults and E. melanopterus sub-adults differed significantly in density and biomass between areas of the estuary. Both the upper estuary, during the late dry season, and the middle estuary, during the early rainy season, functioned as nursery habitats for E. brasilianus. During the early rainy season and dry season, the beaches were a nursery for the E. melanopterus. The concentration of these ontogenetic phases was mainly related to the dissolved oxygen and salinity gradients of the estuary, which drive not only gerreid movement between estuarine habitats but also moves the habitats. This study reinforces the importance of conserving the habitats of the Goiana Estuary so that species such as gerreids can complete their life cycle in the face of pressure from anthropogenic activities, such as mangrove forest deforestation, overfishing, fish contamination by plastic ingestion and domestic effluent disposal. PMID- 26887636 TI - Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis. AB - Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID- 26887638 TI - Considerable loss of information on skin cancer occurrence and non-adherence to clinical practice guideline in renal transplant recipients. PMID- 26887641 TI - Highly ordered surfactant micelles function as the extraction matrix for direct electrochemical detection of halonitrobenzenes at the ppb level. AB - Halonitrobenzenes (HNBs) are a class of molecules that are highly toxic to human health and the ecological environment. Thus, effective and efficient approaches capable of monitoring and detecting HNBs are greatly desired. We report herein a simple and sensitive method for the detection of HNBs. The detection was based on the indium tin oxide (ITO) electrodes modified with a binary assembly of highly ordered surfactant micelles (OSMs) and silica mesochannels (SMs). The SMs have a diameter of 2-3 nm and a vertical orientation, which provide a hard support to stabilize soft OSMs. Moreover, each OSM consists of a hydrophobic core due to the organized assembly of surfactant hydrocarbon chains, which can selectively extract and concentrate lipophilic HNBs from aqueous media, allow their transport to the underlying ITO electrode surface and therein their detection by voltammetry. As a proof-of-concept experiment, 1-chloro-3-nitrobenzene, 1-chloro 4-nitrobenzene, 1-bromo-4-nitrobenzene and 2,4-dinitrobromobenzene were analyzed in aqueous solutions. A simple and fast detection was achieved in all cases, with a wide linear dynamic range, a high sensitivity and a low limit of detection at the ppb level. Apart from the extraction ability, the OSMs also prohibited the access of and surface contamination by unwanted substances, showing excellent anti-fouling and anti-interference power. Indeed, as we demonstrated, the sensor could be employed for direct electrochemical detection of HNBs in complex samples, such as lake water and soil dispersion, without any pre-treatment, indicating its potential usefulness in practical analysis. PMID- 26887639 TI - Temporal dynamics of Puumala hantavirus infection in cyclic populations of bank voles. AB - Understanding the dynamics of zoonotic pathogens in their reservoir host populations is a prerequisite for predicting and preventing human disease epidemics. The human infection risk of Puumala hantavirus (PUUV) is highest in northern Europe, where populations of the rodent host (bank vole, Myodes glareolus) undergo cyclic fluctuations. We conducted a 7-year capture-mark recapture study to monitor seasonal and multiannual patterns of the PUUV infection rate in bank vole populations exhibiting a 3-year density cycle. Infected bank voles were most abundant in mid-winter months during years of increasing or peak host density. Prevalence of PUUV infection in bank voles exhibited a regular, seasonal pattern reflecting the annual population turnover and accumulation of infections within each year cohort. In autumn, the PUUV transmission rate tracked increasing host abundance, suggesting a density dependent transmission. However, prevalence of PUUV infection was similar during the increase and peak years of the density cycle despite a twofold difference in host density. This may result from the high proportion of individuals carrying maternal antibodies constraining transmission during the cycle peak years. Our exceptionally intensive and long-term dataset provides a solid basis on which to develop models to predict the dynamic public health threat posed by PUUV in northern Europe. PMID- 26887642 TI - Strange Bedfellows? Common Ground on the Moral Status Question. AB - When does a developing human being acquire moral status? I outline three different positions based on substance ontology that attempt to solve the question by locating some morally salient event in the process of human development question. In the second section, I consider some specific empirical objections to one of these positions, refute them, and then show how similar objections and responses would generalize to the other substance-based positions on the question. The crucial finding is that all the attempts to answer the question that involve substance ontology need to appeal to dispositions. PMID- 26887643 TI - A Radio-genomics Approach for Identifying High Risk Estrogen Receptor-positive Breast Cancers on DCE-MRI: Preliminary Results in Predicting OncotypeDX Risk Scores. AB - To identify computer extracted imaging features for estrogen receptor (ER) positive breast cancers on dynamic contrast enhanced (DCE)-MRI that are correlated with the low and high OncotypeDX risk categories. We collected 96 ER positive breast lesions with low (< 18, N = 55) and high (> 30, N = 41) OncotypeDX recurrence scores. Each lesion was quantitatively characterize via 6 shape features, 3 pharmacokinetics, 4 enhancement kinetics, 4 intensity kinetics, 148 textural kinetics, 5 dynamic histogram of oriented gradient (DHoG), and 6 dynamic local binary pattern (DLBP) features. The extracted features were evaluated by a linear discriminant analysis (LDA) classifier in terms of their ability to distinguish low and high OncotypeDX risk categories. Classification performance was evaluated by area under the receiver operator characteristic curve (Az). The DHoG and DLBP achieved Az values of 0.84 and 0.80, respectively. The 6 top features identified via feature selection were subsequently combined with the LDA classifier to yield an Az of 0.87. The correlation analysis showed that DHoG (rho = 0.85, P < 0.001) and DLBP (rho = 0.83, P < 0.01) were significantly associated with the low and high risk classifications from the OncotypeDX assay. Our results indicated that computer extracted texture features of DCE-MRI were highly correlated with the high and low OncotypeDX risk categories for ER-positive cancers. PMID- 26887644 TI - Improving seedless kelp (Saccharina japonica) during its domestication by hybridizing gametophytes and seedling-raising from sporophytes. AB - Dongfang no.7 (Saccharina japonica) was bred and maintained by hybridizing gametophytes, self-crossing the best individuals, selecting the best self crossing line and seedling-raising from yearly reconstructed sporophytes. It increased the air dry yield by 43.2% in average over 2 widely farmed controls. Dongfang no.7 was seedling-raised from bulked sporophytes reconstructed from its representative gametophyte clones. Such strategy ensured it against variety contamination due to possible cross fertilization and occasional mixing and inbred depletion due to self-crossing number-limited sporophytes year after year. It derived from an intraspecific hybrid through 4 rounds of self-crossing and selection and retained a certain degree of genetic heterozygosity, thus being immune to inbred depletion due to purification of unknown detrimental alleles. Most importantly, it can be farmed in currently available system as the seedlings for large scale culture can be raised from reconstructed Dongfang no.7 sporophytes. Breeding and maintaining Dongfang no.7 provided a model that other varieties of kelp (S. japonica) and brown algae may follow during their domestication. PMID- 26887645 TI - Efficacy of Transforaminal Endoscopic Spine System (TESSYS) Technique in Treating Lumbar Disc Herniation. AB - BACKGROUND To compare efficacy and safety of percutaneous transforaminal endoscopic spine system (TESSYS) and traditional fenestration discectomy (FD) in treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS A total of 106 LDH patients were divided into TESSYS group (n=48) and FD group (n=58). Visual analogue scale (VAS), Oswestry disability index (ODI), Japanese Orthopedic Association (JOA), and modified MacNab criteria were used for efficacy evaluation. Post-operative responses were compared by enzyme-linked immunosorbent assay (ELISA) based on detection of serum IL-6, CRP, and CPK levels. RESULTS In the TESSYS group, compared with the FD group, we observed, shorter incision length, less blood loss, shorter hospital stay, lower hospitalization cost, shorter recovery time, lower complication rate (all P<0.001), and lower VAS scores of lumbago and skelalgia at 3 days and 1, 3, and 6 months postoperatively (all P<0.05). At 24 and 48 h postoperatively, CRP level was remarkably higher in the FD group compared to the TESSYS group (P<0.001). Further, comparison of IL-6 levels at 6, 12, 24, and 48 h postoperatively revealed significantly higher levels in the FD group than in the FESSYS group (all P<0.001). CONCLUSIONS TESSYS had clinical advantages over FD and entails less trauma and quicker postoperative recovery, suggesting that TESSYS is well tolerated by patients and is a better approach than FD in surgical treatment of LDH. PMID- 26887646 TI - Trypanosoma evansi in naturally infected dromedary camels: lipid profile, oxidative stress parameters, acute phase proteins and proinflammatory cytokines. AB - Additional biomarkers are essential for control of Trypanosoma evansi (T. evansi) infection in dromedary camels. Two groups of 30 camels each, one naturally infected with T. evansi and other normal healthy were executed. The basis for the infection was the positive findings of clinical examination, blood smears and latex agglutination test. Blood samples of both groups and its harvested serum were used for the estimation of present serobiochemical parameters. The present findings revealed significant decrease (P ? 0.05) in triacylglycerol, cholesterol, high density lipoprotein cholesterol with significant increase (P ? 0.05) in low density lipoprotein cholesterol, beta hydroxyl butyric acids, non esterified fatty acids, haptoglobin, serum amyloid A, ceruloplasmin, fibrinogen, interleukins, tumour necrosis factor-alpha, interferon gamma, malondialdehyde, superoxide dismutase, reduced glutathione and catalase of infected camels compared with the control. The present study suggests lipid profile, acute phase proteins, proinflammatory cytokines and oxidative stress parameters as biomarkers for T. evansi infection in camels. PMID- 26887647 TI - Comparative assay of Vipera ammodytes antivenom potency. AB - The finding of the most appropriate way to assess precisely the antivenom efficacy represents one of the major issues for antivenom standardization and success increasing of antivenom therapy. The efficacy of experimental Vipera ammodytes antivenom raised in sheep was determined using in vivo mouse lethality test, respectively, L-aminoacid oxidase, total proteinase and phospholipase A2 antienzymatic effectiveness. The values gained for the antivenom potency depend on the method of measure. So, some of the most toxic venom proteins own phospholipase A2 activity and provide the highest antivenom potency (lowest effective dose) values by antienzymatic assay method. This value is similar with total antiproteolytic antivenom potency value, but almost three times higher than value obtained by L-aminoacid oxidase (low toxic viper venom protein) antienzymatic assay method. PMID- 26887648 TI - Dietary patterns in early childhood and child cognitive and psychomotor development: the Rhea mother-child cohort study in Crete. AB - Early-life nutrition is critical for optimal brain development; however, few studies have evaluated the impact of diet as a whole in early childhood on neurological development with inconsistent results. The present analysis is a cross-sectional study nested within an ongoing prospective birth cohort, the Rhea study, and aims to examine the association of dietary patterns with cognitive and psychomotor development in 804 preschool (mean age 4.2 years) children. Parents completed a validated FFQ, and dietary patterns were identified using principal component analysis. Child cognitive and psychomotor development was assessed by the McCarthy Scales of Children's Abilities (MSCA). Multivariable linear regression models were used to investigate the associations of dietary patterns with the MSCA scales. After adjustment for a large number of confounding factors, the 'Snacky' pattern (potatoes and other starchy roots, salty snacks, sugar products and eggs) was negatively associated with the scales of verbal ability (beta=-1.31; 95 % CI -2.47, -0.16), general cognitive ability (beta=-1.13; 95 % CI -2.25, -0.02) and cognitive functions of the posterior cortex (beta=-1.20; 95 % CI -2.34, -0.07). Further adjustment for maternal intelligence, folic acid supplementation and alcohol use during pregnancy attenuated the observed associations, but effect estimates remained at the same direction. The 'Western' and the 'Mediterranean' patterns were not associated with child neurodevelopmental scales. The present findings suggest that poorer food choices at preschool age characterised by foods high in fat, salt and sugar are associated with reduced scores in verbal and cognitive ability. PMID- 26887649 TI - Quality of serious adverse events reporting to academic sponsors of clinical trials: far from optimal. AB - PURPOSE: The purpose of this study is to evaluate the quality of the serious adverse events (SAE) reported to an academic sponsor. Assessing the safety of a clinical trial relies on information gathering the collection of adverse events reported by the investigators to the sponsor. The accuracy of safety evaluation depends in particular on the quality of the reporting. METHODS: All SAE case report forms, reported in 2012 to the sponsor from all clinical trials, were evaluated for completeness and accuracy with a standardized data quality evaluation form. Several items were assessed: regulatory mandatory information and items concerning the reported events. For statistical comparisons, Chi2/exact Fisher test was performed. RESULTS: Investigators or patients were not identified in <3% of the reports. The investigational product was not identified in 11.2%. In 3.6% of the reports, the seriousness of the event was unknown. The causality assessment was missing in 9.3%. In 15.0%, the verbatim of the event was considered as not consistent with the description of the event. In 32.4%, the sponsor considered there were insufficient data concerning relevant laboratory/additional examinations performed or relevant history required to help in the assessment. The onset date of SAE was not mentioned in 5.7% of the reports and patient outcome in 12.1%. CONCLUSIONS: This study highlighted the far from optimal quality of reporting both in terms of completeness and accuracy. The accurate coding of the events using MedDRA and the safety evaluation by the sponsor can be difficult. The training of investigators in SAE reporting must be improved. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887650 TI - Breast cancer literacy among higher secondary students: results from a cross sectional study in Western Nepal. AB - BACKGROUND: Being the most common cancer among women worldwide, it is vital to be well-aware of breast cancer risk factors, symptoms and curability. However, few studies have reported breast cancer literacy in students using a validated instrument. METHODS: A cross-sectional study was conducted among students of grades 11 and 12 from eleven higher secondary schools, one selected randomly from each ilaka of Parbat district. Questionnaire with modified Comprehensive Breast Cancer Knowledge Test was self-administered to 516 students. Knowledge score was categorized into two categories: 'good knowledge' and 'poor knowledge' taking median score as the cut-off. Chi-square test was used to determine difference in knowledge by socio-demographic factors, including gender. RESULTS: Only 4.8% of the students responded correctly to at least half of the items, and 1.4% did not respond correctly to any of the items on risk factors and curability. Physical exercise was identified as a protective factor of breast cancer by 62.4% of the students. Presence of noncancerous breast lumps (56.6%) and being overweight (36.4%) were recognized as the risk factors. Knowledge of lumpectomy and radiation therapy for treatment of breast cancer was reported by 42.8% of students, while only 39.0% were aware of the availability of treatment therapies other than mastectomy. Males were significantly better informed than females (chi(2) = 4.02, p = 0.045). Pain in the breast (23.3 %), change in the shape of the breast (20.0%) and discharge of pus (14.1%) were the three most commonly recognized symptoms. Nearly one in two (47.1%) students indicated that the school curriculum inadequately informed them on breast cancer. CONCLUSION: Our study demonstrates poor knowledge on breast cancer risk factors, symptoms and curability among higher secondary school students in Western Nepal. Still, several myths regarding breast cancer persist. Half of the students had the perception that school curriculum inadequately informed them on breast cancer. Future studies should aim at the measures necessary to address the inadequate knowledge, along with the perceived gap in school curriculum. PMID- 26887651 TI - Pharmacokinetics and N-acetylation metabolism of S-methyl-l-cysteine and trans-S 1-propenyl-l-cysteine in rats and dogs. AB - 1. Pharmacokinetics and N-acetylation metabolism of S-methyl-L-cysteine (SMC) and trans-S-1-propenyl-L-cysteine (S1PC) were examined in rats and dogs. SMC and S1PC (2-5 mg/kg) were well absorbed in both species with high bioavailability (88 100%). 2. SMC and S1PC were excreted only to a small extent in the urine of rats and dogs. The small renal clearance values (<0.03 l/h/kg) indicated the extensive renal reabsorption of SMC and S1PC, which potentially contributed to their long elimination half-lives (>5 h) in dogs. 3. S1PC, but not SMC, underwent N acetylation extensively in vivo, which can be explained by the relative activities of N-acetylation of S1PC/SMC and deacetylation of their N-acetylated forms, N-acetyl-S1PC/N-acetyl-SMC, in the liver and kidney in vitro. The activities for S1PC N-acetylation were similar to or higher than those for N acetyl-S1PC deacetylation in liver S9 fractions of rat and dog, whereas liver and kidney S9 fractions of rat and dog had little activity for SMC N-acetylation or considerably higher activities for N-acetyl-SMC deacetylation. 4. Our study demonstrated that the pharmacokinetics of SMC and S1PC in rats and dogs was characterized by high bioavailability and extensive renal reabsorption; however, the extent of undergoing the N-acetylation metabolism was extremely different between SMC and S1PC. PMID- 26887653 TI - The impact of clinical librarian services on patients and health care organisations. AB - BACKGROUND: Systematic reviews have found limited evidence of effectiveness and impact of clinical librarians (CLs) due to the poor quality of reporting, scale and design of previous studies. OBJECTIVES: To measure specific CL impact on organisational and patient outcomes using a robust approach that helps CLs develop research skills. METHODS: Questionnaire and interviews. RESULTS: Clinical librarians contribute to a wide range of outcomes in the short and longer term reflecting organisational priorities and objectives. These include direct contributions to choice of intervention (36%) diagnosis (26%) quality of life (25%), increased patient involvement in decision making (26%) and cost savings and risk management including avoiding tests, referrals, readmissions and reducing length of stay (28%). DISCUSSION: Interventions provided by CL's are complex and each contributes to multiple outcomes of importance to health care organisations. CONCLUSION: This study is unique in taking a wide view of potential and specific impacts to which CLs contribute across health care organisations. It is the largest UK evaluation of CL services to date and demonstrates CLs affect direct patient care, improve quality and save money. Future researchers are urged to use the tools presented to collect data on the same outcomes to build a significant and comprehensive international evidence base about the effectiveness and impact of clinical librarian services. PMID- 26887652 TI - LIN7A is a major determinant of cell-polarity defects in breast carcinomas. AB - BACKGROUND: Polarity defects are a hallmark of most carcinomas. Cells from invasive micropapillary carcinomas (IMPCs) of the breast are characterized by a striking cell polarity inversion and represent an interesting model for the analysis of polarity abnormalities. METHODS: In-depth investigation of polarity proteins in 24 IMPCs and a gene expression profiling, comparing IMPC (n = 73) with invasive carcinomas of no special type (ICNST) (n = 51) have been performed. RESULTS: IMPCs showed a profound disorganization of the investigated polarity proteins and revealed major abnormalities in their subcellular localization. Gene expression profiling experiments highlighted a number of deregulated genes in the IMPCs that have a role in apico-basal polarity, adhesion and migration. LIN7A, a Crumbs-complex polarity gene, was one of the most differentially over-expressed genes in the IMPCs. Upon LIN7A over-expression, we observed hyperproliferation, invasion and a complete absence of lumen formation, revealing strong polarity defects. CONCLUSION: This study therefore shows that LIN7A has a crucial role in the polarity abnormalities associated with breast carcinogenesis. PMID- 26887654 TI - Drug repurposing to target Ebola virus replication and virulence using structural systems pharmacology. AB - BACKGROUND: The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation. RESULTS: One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence of Ebola, and to determine the binding modes with their respective targets. Initial screening has identified a number of promising hits. Notably, Indinavir; an HIV protease inhibitor, may be effective in reducing the virulence of Ebola. Additionally, an antifungal (Sinefungin) and several anti-viral drugs (e.g. Maraviroc, Abacavir, Telbivudine, and Cidofovir) may inhibit Ebola RNA-directed RNA polymerase through targeting the MTase domain. CONCLUSIONS: Identification of safe drug candidates is a crucial first step toward the determination of timely and effective therapeutic approaches to address and mitigate the impact of the Ebola global crisis and future outbreaks of pathogenic diseases. Further in vitro and in vivo testing to evaluate the anti Ebola activity of these drugs is warranted. PMID- 26887655 TI - Comparison of different anticoagulant associations on haemostasis and biochemical analyses in feline blood specimens. AB - Objectives Universal anticoagulant could be an alternative to the multiple blood sampling required for clinical pathology investigations in cats. An association of citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to be a good substitute for EDTA for haematology analysis in cats, limiting platelet clumping, and has also been shown to be valid for haematology, secondary haemostasis and some biochemical variables in humans. The aim of the study was therefore to investigate the effects of CTAD on in vitro platelet aggregation and compare results of secondary haemostasis and biochemistry tests, excluding a priori those variables not reliably measured in CTAD, such as sodium, chloride and divalent cations, in feline blood specimens collected in CTAD and paired citrate and heparin tubes. Methods Thirty blood specimens sampled in citrate and CTAD were analysed for in vitro platelet aggregation, and 60 blood specimens sampled in citrate or heparin and CTAD were analysed for plasma coagulation and a biochemistry panel. Results In vitro platelet aggregation was inhibited in CTAD compared with citrate specimens. Prothrombin time, activated partial thromboplastin time, antithrombin and fibrinogen results were similar, despite some significant differences. Measurements of triglycerides, cholesterol, glucose, urea, creatinine, phosphate, total proteins and alanine aminotransferase activity were similar and well correlated in CTAD and heparin plasmas, despite some significant differences and moderate biases. Albumin showed a marked positive proportional bias, and creatine kinase and alkaline phosphatase activities a moderate and marked negative mixed bias, respectively, but could be measured in CTAD if new reference intervals were calculated. Aspartate aminotransferase activity showed a marked negative proportional bias, along with a poor correlation and some clinical misclassifications just like the potassium concentration, and thus cannot be recommended to be measured in CTAD specimens. Conclusions and relevance In cats, CTAD cannot be used for primary haemostasis investigation but could be a suitable (almost) universal anticoagulant for routine haematology, as well as for plasma coagulation and many biochemistry variables. PMID- 26887658 TI - Giant absorption of light by molecular vibrations on a chip. AB - Vibrational overtone spectroscopy of molecules is a powerful tool for drawing information on molecular structure and dynamics. It relies on absorption of near infrared radiation (NIR) by molecular vibrations. Here we show the experimental evidence of giant enhancement of the absorption of light in solutions of organic molecules due to the switch from ballistic to diffusive propagation of light through a channel silicate glass waveguide. We also experimentally address a dynamics of absorption as a function of time of adsorption of the organic molecules on a waveguide. The observed enhancement in diffusion regime is by a factor of 300 in N-Methylaniline and by factor of 80 in Aniline compared to the expected values in the case of ballistic propagation of light in a waveguide. Our results underscore the importance of a guide surface modification and the disordered molecular nano-layer in enhancement of absorption by amines on engineered integrated system. PMID- 26887656 TI - Cryptococcus neoformans Intracellular Proliferation and Capsule Size Determines Early Macrophage Control of Infection. AB - Cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. Many questions remain regarding the function of macrophages in normal clearance of cryptococcal infection and the defects present in uncontrolled cryptococcosis. Two current limitations are: 1) The difficulties in interpreting studies using isolated macrophages in the context of the progression of infection, and 2) The use of high resolution imaging in understanding immune cell behavior during animal infection. Here we describe a high-content imaging method in a zebrafish model of cryptococcosis that permits the detailed analysis of macrophage interactions with C. neoformans during infection. Using this approach we demonstrate that, while macrophages are critical for control of C. neoformans, a failure of macrophage response is not the limiting defect in fatal infections. We find phagocytosis is restrained very early in infection and that increases in cryptococcal number are driven by intracellular proliferation. We show that macrophages preferentially phagocytose cryptococci with smaller polysaccharide capsules and that capsule size is greatly increased over twenty-four hours of infection, a change that is sufficient to severely limit further phagocytosis. Thus, high-content imaging of cryptococcal infection in vivo demonstrates how very early interactions between macrophages and cryptococci are critical in the outcome of cryptococcosis. PMID- 26887657 TI - Asia-Pacific Hematology Consortium Report on approach to multiple myeloma. Survey results from the 6th International Hematologic Malignancies Conference: Bridging the Gap 2015, Beijing, China. AB - The Asia-Pacific Hematology Consortium (APHCON), in partnership with MDRingTM, a mobile global physician education network, has initiated a detailed longitudinal study of physician knowledge and practice preferences in the Asia-Pacific sphere. The first dataset comes from a series of surveys answered by delegates at the APHCON Bridging The Gap (BTG) conference in Beijing in January, 2015. In this report we present our findings regarding diagnosis and treatment of multiple myeloma (MM). We aim to create a conduit for physicians in this region to share their experiences with the rest of the world, to identify areas of consensus and best practices, and to highlight opportunities for improvement in communication, education and patient care. PMID- 26887659 TI - Quantitative susceptibility mapping at 3 T: comparison of acquisition methodologies. AB - Quantitative susceptibility mapping (QSM) is fast becoming a routine clinical tool in the evaluation and assessment of neurological diseases. Unfortunately, there is currently no established standard scanning protocol, and it is uncertain whether different acquisition strategies alter the derived estimates of magnetic susceptibility. Here, we compare some key deep grey matter susceptibility values in healthy adults acquired from various QSM sequences using either unipolar or bipolar readout gradients, accelerated imaging or not, and gradient-warp correction or not. Four healthy adult volunteers were scanned three times each within 4 days at 3 T. The eight different QSM combinations were acquired in different randomised order for each session, and then co-registered to an anatomical atlas. The average and standard deviations of magnetic susceptibilities in the caudate, putamen, red nucleus, internal and external globus pallidus were used in a linear mixed effects model to determine the influence of the various acquisition parameters. Gradient-warp correction was the only statistically significant fixed effect (p < 0.01), but its impact was small (~5% change) compared with the overall fixed effects. The random effects coefficients (i.e. the various tissues) were statistically significant. Based on our limited multiple observations in healthy adult volunteers, the susceptibilities in deep grey matter are statistically equivalent when QSM source data are acquired with or without accelerated imaging using either unipolar or bipolar readout gradients. There is, however, a statistically meaningful, but small, difference if gradient-warp correction is used or not. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887660 TI - Salinity drives archaeal distribution patterns in high altitude lake sediments on the Tibetan Plateau. AB - Archaeal communities and the factors regulating their diversity in high altitude lakes are poorly understood. Here, we provide the first high-throughput sequencing study of Archaea from Tibetan Plateau lake sediments. We analyzed twenty lake sediments from the world's highest and largest plateau and found diverse archaeal assemblages that clustered into groups dominated by methanogenic Euryarchaeota, Crenarchaeota and Halobacteria/mixed euryarchaeal phylotypes. Statistical analysis inferred that salinity was the major driver of community composition, and that archaeal diversity increased with salinity. Sediments with the highest salinities were mostly dominated by Halobacteria. Crenarchaeota dominated at intermediate salinities, and methanogens were present in all lake sediments, albeit most abundant at low salinities. The distribution patterns of the three functional types of methanogens (hydrogenotrophic, acetotrophic and methylotrophic) were also related to changes in salinity. Our results show that salinity is a key factor controlling archaeal community diversity and composition in lake sediments on a spatial scale that spans nearly 2000 km on the Tibetan Plateau. PMID- 26887661 TI - Quantification of the effects of ocean acidification on sediment microbial communities in the environment: the importance of ecosystem approaches. AB - To understand how ocean acidification (OA) influences sediment microbial communities, naturally CO2-rich sites are increasingly being used as OA analogues. However, the characterization of these naturally CO2-rich sites is often limited to OA-related variables, neglecting additional environmental variables that may confound OA effects. Here, we used an extensive array of sediment and bottom water parameters to evaluate pH effects on sediment microbial communities at hydrothermal CO2 seeps in Papua New Guinea. The geochemical composition of the sediment pore water showed variations in the hydrothermal signature at seep sites with comparable pH, allowing the identification of sites that may better represent future OA scenarios. At these sites, we detected a 60% shift in the microbial community composition compared with reference sites, mostly related to increases in Chloroflexi sequences. pH was among the factors significantly, yet not mainly, explaining changes in microbial community composition. pH variation may therefore often not be the primary cause of microbial changes when sampling is done along complex environmental gradients. Thus, we recommend an ecosystem approach when assessing OA effects on sediment microbial communities under natural conditions. This will enable a more reliable quantification of OA effects via a reduction of potential confounding effects. PMID- 26887662 TI - Meeting individualized glycemic targets in primary care patients with type 2 diabetes in Spain. AB - BACKGROUND: Information about the achievement of glycemic targets in patients with type 2 diabetes according to different individualization strategies is scarce. Our aim was to analyze the allocation of type 2 diabetic patients into individualized glycemic targets according to different strategies of individualization and to assess the degree of achievement of adequate control. METHODS: Cross-sectional analysis on 5382 type 2 diabetic patients in primary care setting in Spain between 2011 and 2012. Targets of HbA1c were assigned based on different strategies of individualization of glycemic targets: 1) the ADA/EASD consensus 2) The Spanish Diabetes Society (SED) consensus 3) a strategy that accounts for the risk of hypoglycemia (HYPO) considering the presence of a hypoglycemia during the last year and type of hypoglycemic treatment. Concordance between the different strategies was analyzed. RESULTS: A total of 15.9, 17.1 and 67 % applied to ADA/EASD recommendation of HbA1c target of <6.5, < 7 and <8 % (48, 53 and 64 mmol/mol), and 31.9 and 67.4 % applied to the SED glycemic target of <6.5 and <7.5 % (<48 and 58 mmol/mol). Using the HYPO strategy, 53.5 % had a recommended HbA1c target <7 % (53 mmol/mol). There is a 94 % concordance between the ADA/EASD and SED strategies, and a concordance of 41-42 % between these strategies and HYPO strategy. Using the three different strategies, the overall proportion of patients achieving glycemic targets was 56-68 %. CONCLUSIONS: Individualization of glycemic targets increases the number of patients who are considered adequately controlled. The proposed HYPO strategy identifies a similar proportion of patients that achieve adequate glycemic control than ADA/EASD or SED strategies, but its concordance with these strategies in terms of patient classification is bad. PMID- 26887663 TI - Effect of metformin therapy on circulating amino acids in a randomized trial: the CAMERA study. AB - AIMS: To investigate whether metformin therapy alters circulating aromatic and branched-chain amino acid concentrations, increased levels amino acid concentrations, increased levels of which have been found to predict Type 2 diabetes. METHODS: In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months. Plasma samples, taken every 6 months, were analysed using quantitative nuclear magnetic resonance spectroscopy. Ten metabolites consisting of eight amino acids [three branched-chain (isoleucine, leucine, valine), three aromatic (tyrosine, phenylalanine, histidine) and two other amino acids (alanine, glutamine)], lactate and pyruvate were quantified and analysed using repeated measures models. On-treatment analyses were conducted to investigate whether amino acid changes were dependent on changes in weight, fat mass or insulin resistance estimated using homeostasis model assessment (HOMA-IR). RESULTS: Tyrosine decreased [-6.1 MUmol/l (95% CI -8.5, -3.7); P<0.0001], while alanine [42 umol/l (95% CI 25, 59); P<0.0001] increased in the metformin-treated group compared with the placebo-treated group. Decreases in phenylalanine [-2.0 MUmol/l (95% CI -3.6, -0.3); P=0.018] and increases in histidine [2.3 MUmol/l (95% CI 0.1, 4.6); P=0.045] were also observed in the metformin group, although these changes were less statistically robust. Changes in these four amino acids were not accounted for by changes in weight, fat mass or HOMA-IR values. Levels of branched-chain amino acids, glutamine, pyruvate and lactate were not altered by metformin therapy. CONCLUSIONS: Metformin therapy results in a sustained and specific pattern of changes in aromatic amino acid and alanine concentrations. These changes are independent of any effects on weight and insulin sensitivity. Any causal link to metformin's unexplained cardiometabolic benefit requires further study. PMID- 26887664 TI - Recurrent event data analysis with intermittently observed time-varying covariates. AB - Although recurrent event data analysis is a rapidly evolving area of research, rigorous studies on estimation of the effects of intermittently observed time varying covariates on the risk of recurrent events have been lacking. Existing methods for analyzing recurrent event data usually require that the covariate processes are observed throughout the entire follow-up period. However, covariates are often observed periodically rather than continuously. We propose a novel semiparametric estimator for the regression parameters in the popular proportional rate model. The proposed estimator is based on an estimated score function where we kernel smooth the mean covariate process. We show that the proposed semiparametric estimator is asymptotically unbiased, normally distributed, and derives the asymptotic variance. Simulation studies are conducted to compare the performance of the proposed estimator and the simple methods carrying forward the last covariates. The different methods are applied to an observational study designed to assess the effect of group A streptococcus on pharyngitis among school children in India. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887665 TI - Tibiocalcaneal arthrodesis as a limb salvage procedure for complex hindfoot deformities. AB - INTRODUCTION: Tibiocalcaneal (TC) arthrodesis is a limb salvage method for patients with severe deformities combined with necrosis and/or luxation of the talus. The aim of this study was to examine the clinical and radiological outcome of TC arthrodesis. MATERIALS AND METHODS: This retrospective study identified 12 patients with luxation and/or necrosis of the talus, due to charcot neuroarthropathy (83.3 %) or traumatic injuries (16.7 %). All patients underwent TC arthrodesis by an external fixator or nail arthrodesis. The mean follow up was 18 (6-36) months with a mean age of 51.3 (30-66) years. The data were collected using the AOFAS score as well as clinical and radiological examination during regular follow up. RESULTS: Seven (58.3 %) patients were treated with an external fixator, four (33.3 %) with nail arthrodesis and one (8.3 %) patient rejected both fixation methods. Four (100 %) patients achieved radiological and clinical bone union after nail arthrodesis and four (57.1 %) patients after external fixation. Three (42.9 %) patients treated by an external fixator showed a radiological moderate bone fusion, but a stable, asymptomatic non-union. One (8.3 %) case ended up in transfemoral amputation. Eleven patients (91.7 %) regained independent mobilization. The mean AOFAS score improved from 24.3 preoperatively to 66.7 postoperatively (p < 0.05). The postoperative satisfaction rate was good to excellent in 83.3 %. CONCLUSION: TC arthrodesis is a promising and effective method for the treatment of severe ankle deformities with talus luxation. It allows patient's return to mobility with good to excellent patient satisfaction. PMID- 26887666 TI - N-methylnicotinamide protects against endothelial dysfunction and attenuates atherogenesis in apolipoprotein E-deficient mice. AB - SCOPE: Epidemiological studies have demonstrated that N-methylnicotinamide (MNA) may exert antithrombotic and anti-inflammatory effects on the endothelium. However, the exact role of MNA in endothelial function remains uncertain. METHODS AND RESULTS: Apolipoprotein E-deficient (apoE(-/-) ) mice fed with a high-fat, high-cholesterol diet (HCD) and human umbilical vein endothelial cells (HUVECs) were used to explore the role of MNA in endothelial function and its underlying mechanism. The endothelium-dependent vasorelaxation to acetylcholine in the aortas of low and high dose MNA-fed apoE(-/-) mice was improved by 24 and 36% (p < 0.05), respectively, compared with high-fat, HCD-fed control. MNA significantly increased nitric oxide/cyclic guanosinemonophosphate levels and decreased asymmetric dimethylarginine (ADMA) concentrations by induction of dimethylarginine dimethylaminohydrolase (DDAH)2 both in aorta and endothelial cells. Neither the activity nor the protein expression of DDAH1 was influenced upon MNA treatment. Then, DDAH2 depletion by RNA interference in HUVECs abolished the protective effect of MNA on endothelial function. Mechanically, this could be attributed to a direct modulation of the methylation level of DDAH2 gene promoter region by MNA. CONCLUSIONS: The present study reveals a novel mechanism through which MNA improves endothelial dysfunction and attenuates atherogenesis via the modulation of ADMA-DDAH axis. PMID- 26887667 TI - Effect of Balloon:Annulus Ratio on Incidence of Pulmonary Insufficiency Following Valvuloplasty. AB - OBJECTIVE: Pulmonary insufficiency following balloon valvuloplasty for pulmonary valve stenosis has been shown to result in right ventricular dilation, which may necessitate pulmonary valve replacement. This study investigates the consequences of employing a more conservative balloon:annulus ratio of <=1.2 against the currently used ratios of >1.2. The aim of the study was to evaluate whether a more conservative balloon:annulus ratio would maintain procedural success with adequate relief of the pulmonary valve gradient, while minimizing pulmonic insufficiency. DESIGN: Procedural data were collected on cases considered for balloon valvuloplasty for congenital pulmonic stenosis at Rady Children's Hospital, San Diego between March 31, 2003 and April 9, 2014. The study includes 98 patients whose median age at the time of procedure was 3.6 months (range: 1 day to 271 months); median follow-up was 15.2 months (range 24 days to 106 months). The subjects were divided into two groups based on their balloon:annulus ratio: <=1.2 (n = 67) and >1.2 (n = 31). RESULTS: The difference in pulmonary gradient reduction-the marker of procedural success-was not significant between the two groups (P = .33). Although both groups had an increase in pulmonary valve insufficiency from baseline, the <=1.2 group had significantly less insufficiency compared to the >1.2 group (P = .008). Reintervention rates were not statistically significant between both groups (P = .89). CONCLUSION: Performing pulmonary balloon valvuloplasty with a balloon:annulus ratio of <=1.2 produces significantly less pulmonary insufficiency than a ratio of >1.2 without reducing procedure efficacy. PMID- 26887668 TI - The applicability of chemical alternatives assessment for engineered nanomaterials. AB - The use of alternatives assessment to substitute hazardous chemicals with inherently safer options is gaining momentum worldwide as a legislative and corporate strategy to minimize consumer, occupational, and environmental risks. Engineered nanomaterials represent an interesting case for alternatives assessment approaches, because they can be considered both emerging "chemicals" of concern, as well as potentially safer alternatives to hazardous chemicals. However, comparing the hazards of nanomaterials to traditional chemicals or to other nanomaterials is challenging, and critical elements in chemical hazard and exposure assessment may have to be fundamentally altered to sufficiently address nanomaterials. The aim of this paper is to assess the overall applicability of alternatives assessment methods for nanomaterials and to outline recommendations to enhance their use in this context. The present paper focuses on the adaptability of existing hazard and exposure assessment approaches to engineered nanomaterials as well as strategies to design inherently safer nanomaterials. We argue that alternatives assessment for nanomaterials is complicated by the sheer number of nanomaterials possible. As a result, the inclusion of new data tools that can efficiently and effectively evaluate nanomaterials as substitutes is needed to strengthen the alternatives assessment process. However, we conclude that with additional tools to enhance traditional hazard and exposure assessment modules of alternatives assessment, such as the use of mechanistic toxicity screens and control banding tools, alternatives assessment can be adapted to evaluate engineered nanomaterials as potential substitutes for chemicals of concern and to ensure safer nanomaterials are incorporated in the design of new products. Integr Environ Assess Manag 2017;13:177-187. (c) 2016 SETAC. PMID- 26887669 TI - Atrophic hepatocytes express keratin 7 in ischemia-associated liver lesions. AB - AIM: To investigate atrophic parenchymal changes in ischemic liver conditions. DESIGN: We studied 18 cases of hepatic lesions with atrophic changes due to altered blood flow (hepatic venous congestion n=15 including 4 cases with additional nodular regenerative hyperplasia-NRH, NRH n=1, and antiphospholipid syndrome with patchy parenchymal atrophy n=2). Metaplastic hepatocellular changes, hepatocyte proliferation, hepatic stellate cell (HSC) activation, and sinusoidal capillarization were examined immunohistochemically with antibodies to keratins (K) 7 and 19, Ki67, alphaSMA and CD34, respectively. RESULTS: K7 was positive and K19 was negative in zone 3 atrophic hepatocytes in venous congestion and in areas of plate atrophy, as well as in congested or compressed sites in NRH. Sinusoidal CD34-positivity indicating capillarization accompanied K7 immunoexpression. Masson trichrome revealed sinusoidal fibrosis to be restricted in atrophic areas, usually mild and in 7 cases focally dense. alphaSMA expression expanded beyond K7-positive areas. Ki67 was negative in K7-positive hepatocytes. CONCLUSION: Ischemic parenchymal changes are characterized by hepatocyte K7 immunoexpression, sinusoidal capillarization, HSC activation and lack of cellular proliferation, indicating an early reaction of the major liver parenchyma cellular components creating a more resistant microenvironment. These phenotypic alterations may prove valuable in the discrimination of ischemic liver lesions. PMID- 26887670 TI - When and How to "Open" in Laparoscopic or Robotic Surgery. AB - INTRODUCTION: Surgical training today is all about minimally invasive surgery. With little or no experience and/or confidence in rapid, emergent conversion to an open procedure, how does the surgeon expeditiously do so? OBJECTIVES: The intent of this paper is to help those inexperienced in "open" techniques to quickly recognize the need for same and rapidly open and temporarily control an acute hemorrhage or significant problem requiring more than the tips of laparoscopic instruments. METHODS: The left subcostal or high transverse incision has been used by this author and several others with an experience of several thousand open cases. The author's emergent technique includes a 3-cm mid-line incision from the xiphoid inferiorly, extending into a 135 degrees left subcostal "hockey stick" approximately 12 cm in length, large enough for the surgeon's fist to rapidly apply a tamponading moist lap sponge. Extension of the incision and rectus muscle bleeding is then controlled before proceeding. RESULTS: This author has used the left subcostal incision in over 4000 bariatric cases over a 30-year career with an incisional hernia and major wound infection rates of less than 1%. CONCLUSION: Today, the laparoscope has virtually replaced all open GS visceral techniques which are de-emphasized in surgical training programs. This author's experience demonstrates a rapid fire technique, which will assist the inexperienced open surgeon in dealing with a very treatable acute complication and preventing a long-term disaster with a huge mid-line wound infection, dehiscence, and ultimate hernia. PMID- 26887671 TI - The Hindlimb Myology of Tyto alba (Tytonidae, Strigiformes, Aves). AB - This work is the first myological dissection performed in detail on the hindlimb of Tyto alba. Six specimens were dissected and their muscle masses were obtained. T. alba has the classical myological pattern present in other species of Strigiformes, such as a well-developed m. flexor digitorum longus and the absence of the m. plantaris, flexor cruris lateralis and ambiens. Also, T. alba lacks the m. extensor propius digiti III, m. extensor propius digiti IV and m. lumbricalis, present in the Strigidae. Hindlimb muscle mass accounts for 14.13% of total body mass, which is within the range of values of both nocturnal (Strigiformes) and diurnal (Falconidae and Accipitridae) raptors. This study provides important information for future studies related to functional morphology and ecomorphology. PMID- 26887672 TI - High prevalence of hypertension and cardiovascular disease risk factors among medical students at Makerere University College of Health Sciences, Kampala, Uganda. AB - BACKGROUND: Cardiovascular disease has become a leading global health challenge representing the largest cause of mortality in adults worldwide. Non communicable diseases are neglected in Uganda over infectious diseases. With increased urbanization, there is likely increase in burden of these NCDs yet there is paucity of reliable data regarding the NCD burden. We assessed the prevalence of hypertension and other cardiovascular disease risk factors among medical students at Makerere University, College of Health Sciences in Kampala, Uganda. METHODS: We conducted a cross-sectional study at Makerere University comprising 180 medical students. We used a standardized questionnaire and anthropometric measurements to assess their cardiovascular disease risk factors using JNC-7. Logistic regression was used to assess factors associated with elevated blood pressure. RESULTS: Of the 180 students surveyed, 107 (59%) were males, mean age was 22 years (SD = 3 years), and 159 (88%) were in their preclinical years of training. Cardiovascular risk factors with the highest prevalence were alcohol consumption (31.7%); elevated systolic blood pressure (14%); and excessive salt intake (13%). Participants with elevated systolic blood pressure were more likely to be older (OR = 1.18), overweight (OR = 1.08), and with a personal history of cardiovascular disease (OR = 4.68). CONCLUSIONS: The prevalence of hypertension and known cardiovascular disease risk factors is high among the medical students. Strategies to prevent cardiovascular disease among the young population should be put in place. PMID- 26887674 TI - Long-term outcomes of hepatic resection for colorectal liver metastases at a New Zealand tertiary level public hospital. AB - BACKGROUND: Colorectal cancer is common with half of all patients developing metastases to the liver. The aim of this study was to document the survival for patients undergoing liver resection for colorectal cancer metastases. METHOD: A review of all patients undergoing hepatic resection for colorectal liver metastases at a New Zealand tertiary level public hospital over a 9-year period was performed. RESULTS: Primary survival outcomes assessed were overall survival (OS) and disease-free survival (DFS). Of the 116 patients followed-up with a median (range) of 53 (10-116) months, the OS at 5 years was 53%. Median survival was 6.5 years. At end of follow-up, 57% of patients were alive and 49% were alive without recurrence. The overall rate of recurrence was 39%. CONCLUSION: This study confirms that excellent long term survival can be achieved with hepatic resection for colorectal liver metastases. PMID- 26887675 TI - An Investigation of the Relationship Between Alcohol Use and Major Depressive Disorder Across Hispanic National Groups. AB - BACKGROUND: There has been consistent epidemiological evidence of the association between drinking, alcohol dependence, and depression. However, most of the research has ignored potential diversity across Hispanic national subgroups. This study examines the prevalence of depression and explores its association with volume of drinking, age at first drink, binge drinking, and alcohol dependence across Mexican American, Puerto Rican, Cuban, and South/Central American Hispanic national groups. METHODS: Data from more than 19,000 Hispanic adults were obtained from the 2010 to 2012 National Survey on Drug Use and Health. Survey logistic regression methods were used to test for differences in the relationship between major depressive disorder (MDD) and alcohol consumption across national groups. RESULTS: The prevalence of MDD varied significantly across Hispanic national groups (chi(2) = 67.06, p < 0.001). Puerto Ricans (14%) and Mexican Americans (9%) were most likely to have MDD. Mexican Americans had the highest prevalence of alcohol dependence, volume of consumption, and youngest age at first drink compared to Puerto Ricans, Cuban Americans, and Central/South Americans. Multivariate results suggest that the odds of alcohol dependence were nearly 4 times greater among Hispanics with MDD compared to Hispanics who did not meet the criteria for MDD. Hispanic national origin did not modify the association between MDD and alcohol use. CONCLUSIONS: Although significant differences in the prevalence rates of MDD and alcohol-use measures emerged across Hispanic national groups, there was no evidence that the relationships between these measures were different across Hispanic national groups. Further research should investigate the root causes of these variable MDD prevalence rates to inform detection and intervention efforts targeted toward specific national groups. PMID- 26887676 TI - Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post Weaning Recovery. AB - During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ~30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism. PMID- 26887677 TI - In Utero Origins of Hypertension: Mechanisms and Targets for Therapy. AB - The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions. PMID- 26887678 TI - Thiol-Disulfide Exchange in Human Growth Hormone. AB - PURPOSE: Thiol-disulfide exchange was monitored in recombinant human growth hormone (hGH) and in model tryptic peptides derived from hGH to investigate the effects of higher-order structure on the reaction. METHODS: Different free thiol containing peptides, varying in length and amino acid sequence, were used to initiate the reaction at pH 7.0 and 37 degrees C in hGH. Protein samples were digested with trypsin and analyzed for native disulfides, scrambled disulfides and free thiols using LC/MS. The loss of native disulfide and disulfide exchange was compared with model peptides derived from hGH. RESULTS: Loss of native disulfide in cyclic (cT20-T21) and linear peptides (T20-T21pep) derived from the C-terminal hGH disulfide during the first 60 min of reaction was greater than loss of the C-terminal disulfide in hGH itself. Of the thiols tested, glutathione (GSH) was the most reactive, forming the highest percentage of mixed disulfides in intact hGH and in the model peptides. At longer reaction times (>240 min), native disulfides in both hGH and cT20-T21 were regenerated. The fastest rates of regeneration were observed for Cys and the di- or tripeptide containing an Arg residue adjacent to Cys, suggesting that they may be useful in refolding. CONCLUSIONS: Thiol-disulfide exchange reactions in hGH and related model peptides were influenced by higher order structure, by the size of the thiol reactant and by an Arg residue adjacent to Cys in the thiol reactant. Reduction of disulfide bonds in hGH did not affect higher order structure as measured by CD and HDX-MS. PMID- 26887679 TI - First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals. AB - PURPOSE: Aerosol particle deposition in the human nasal cavity is of high interest in particular for intranasal central nervous system (CNS) drug delivery via the olfactory cleft. The objective of this study was the development and comparison of a numerical and experimental model to investigate various parameters for olfactory particle deposition within the complex anatomical nasal geometry. METHODS: Based on a standardized nasal cavity, a computational fluid and particle dynamics (CFPD) model was developed that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model. RESULTS: For various flow rates (5 to 40 l/min) and particle sizes (1 to 10 MUm), the airflow velocities, the calculated particle airflow patterns and the particle deposition correlated very well with the experiment. Particle deposition was investigated numerically by varying particle sizes at constant flow rate and vice versa assuming the particle size distribution of the used nebulizer. CONCLUSIONS: The developed CFPD model could be directly translated to the in vitro results. Hence, it can be applied for parameter screening and will contribute to the improvement of aerosol particle deposition at the olfactory cleft for CNS drug delivery in particular for biopharmaceuticals. PMID- 26887680 TI - Insights into Spray Development from Metered-Dose Inhalers Through Quantitative X ray Radiography. AB - PURPOSE: Typical methods to study pMDI sprays employ particle sizing or visible light diagnostics, which suffer in regions of high spray density. X-ray techniques can be applied to pharmaceutical sprays to obtain information unattainable by conventional particle sizing and light-based techniques. METHODS: We present a technique for obtaining quantitative measurements of spray density in pMDI sprays. A monochromatic focused X-ray beam was used to perform quantitative radiography measurements in the near-nozzle region and plume of HFA propelled sprays. RESULTS: Measurements were obtained with a temporal resolution of 0.184 ms and spatial resolution of 5 MUm. Steady flow conditions were reached after around 30 ms for the formulations examined with the spray device used. Spray evolution was affected by the inclusion of ethanol in the formulation and unaffected by the inclusion of 0.1% drug by weight. Estimation of the nozzle exit density showed that vapour is likely to dominate the flow leaving the inhaler nozzle during steady flow. CONCLUSIONS: Quantitative measurements in pMDI sprays allow the determination of nozzle exit conditions that are difficult to obtain experimentally by other means. Measurements of these nozzle exit conditions can improve understanding of the atomization mechanisms responsible for pMDI spray droplet and particle formation. PMID- 26887681 TI - Design principles for rapid folding of knotted DNA nanostructures. AB - Knots are some of the most remarkable topological features in nature. Self assembly of knotted polymers without breaking or forming covalent bonds is challenging, as the chain needs to be threaded through previously formed loops in an exactly defined order. Here we describe principles to guide the folding of highly knotted single-chain DNA nanostructures as demonstrated on a nano-sized square pyramid. Folding of knots is encoded by the arrangement of modules of different stability based on derived topological and kinetic rules. Among DNA designs composed of the same modules and encoding the same topology, only the one with the folding pathway designed according to the 'free-end' rule folds efficiently into the target structure. Besides high folding yield on slow annealing, this design also folds rapidly on temperature quenching and dilution from chemical denaturant. This strategy could be used to design folding of other knotted programmable polymers such as RNA or proteins. PMID- 26887682 TI - Spectral phase measurement of a Fano resonance using tunable attosecond pulses. AB - Electron dynamics induced by resonant absorption of light is of fundamental importance in nature and has been the subject of countless studies in many scientific areas. Above the ionization threshold of atomic or molecular systems, the presence of discrete states leads to autoionization, which is an interference between two quantum paths: direct ionization and excitation of the discrete state coupled to the continuum. Traditionally studied with synchrotron radiation, the probability for autoionization exhibits a universal Fano intensity profile as a function of excitation energy. However, without additional phase information, the full temporal dynamics cannot be recovered. Here we use tunable attosecond pulses combined with weak infrared radiation in an interferometric setup to measure not only the intensity but also the phase variation of the photoionization amplitude across an autoionization resonance in argon. The phase variation can be used as a fingerprint of the interactions between the discrete state and the ionization continua, indicating a new route towards monitoring electron correlations in time. PMID- 26887683 TI - National registration scheme at 5 years: not what it promised. AB - A national registration scheme for health professionals was introduced in Australia 5 years ago, replacing the long-standing state-based schemes. This review examines whether the scheme has delivered what it promised and makes recommendations for change. The available evidence indicates that the scheme's design and its implementation were rushed and that the legislation has serious flaws. Two parliamentary inquiries and the experience of registrants confirm that the system is more expensive, remote and bureaucratic than the previous state based systems. The scheme has delivered benefits only in relation to portability of registration and a single national register. In addition, with two large jurisdictions participating in a 'co-regulated' mode, it is not truly a national scheme. To restore the confidence that health professionals need to have in the regulator, it is recommended that all jurisdictions seek to be 'co-regulated' and that the Australian Health Practitioners Registration Authority be pared back to providing a central database for national portable registration. PMID- 26887684 TI - Assortativity and leadership emerge from anti-preferential attachment in heterogeneous networks. AB - Real-world networks have distinct topologies, with marked deviations from purely random networks. Many of them exhibit degree-assortativity, with nodes of similar degree more likely to link to one another. Though microscopic mechanisms have been suggested for the emergence of other topological features, assortativity has proven elusive. Assortativity can be artificially implanted in a network via degree-preserving link permutations, however this destroys the graph's hierarchical clustering and does not correspond to any microscopic mechanism. Here, we propose the first generative model which creates heterogeneous networks with scale-free-like properties in degree and clustering distributions and tunable realistic assortativity. Two distinct populations of nodes are incrementally added to an initial network by selecting a subgraph to connect to at random. One population (the followers) follows preferential attachment, while the other population (the potential leaders) connects via anti-preferential attachment: they link to lower degree nodes when added to the network. By selecting the lower degree nodes, the potential leader nodes maintain high visibility during the growth process, eventually growing into hubs. The evolution of links in Facebook empirically validates the connection between the initial anti-preferential attachment and long term high degree. In this way, our work sheds new light on the structure and evolution of social networks. PMID- 26887685 TI - Systematic review of the effectiveness of polyurethane-coated compared with textured silicone implants in breast surgery. AB - BACKGROUND: Silicone gel implants are used worldwide for breast augmentation and breast reconstruction. Textured silicone implants are the most commonly placed implant, but polyurethane-coated implants are increasingly being used in an attempt to ameliorate the long-term complications associated with implant insertion. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Electronic searches of MEDLINE, EMBASE, the Cochrane Library and www.ClinicalTrials.gov were undertaken in March 2014 using keywords. RESULTS: Following data extraction, 18 studies were included in the review, including four core studies of textured silicone implants and five studies reporting outcomes for polyurethane-coated silicone implants. There are no clear data reporting revision rates in patients treated with polyurethane implants. In the primary reconstructive setting, capsular contracture rates with silicone implants are 10 15% at 6 years, whilst studies of polyurethane implants report rates of 1.8-3.4%. In the primary augmentation setting, core studies show a capsular contracture rate of 2-15% at 6 years compared with 0.4-1% in polyurethane-coated implants; however, the polyurethane studies are limited by their design and poor follow-up. CONCLUSIONS: The use of polyurethane implants should be considered a safe alternative to textured silicone implants. It is likely that an implant surface does influence short- and long-term outcomes; however, the extent of any benefit cannot be determined from the available evidence base. Future implant studies should target the short- and long-term benefits of implant surfacing by procedure with defined outcome measures; a head-to-head comparison would help clarify outcomes. PMID- 26887686 TI - Frontalis suspension with an expanded polytetrafluoroethylene sheet for congenital ptosis repair. AB - Congenital ptosis with poor levator function is most often repaired with a frontalis suspension procedure. Autogenous fascia lata grafting is generally effective, with low rates of infection and granuloma formation. However, contraction of the grafted fascia lata may cause eyelash inversion, tarsal deformity, and/or lagophthalmos. Conversely, several synthetic suspensory materials have been used for frontalis suspension, among which polytetrafluoroethylene has been reported to be comparable to the fascia lata. However, in some studies using polytetrafluoroethylene strips or sutures, complications such as infection and granuloma formation were a significant problem. This study evaluated the outcomes of frontalis suspension with an expanded polytetrafluoroethylene sheet for congenital ptosis repair in 97 patients (130 eyelids). No ptosis recurrence was reported in an average follow-up of 31.6 months (range: 6-102 months). Six of the 130 eyelids (4.6%) had complications. Based on these results, frontalis suspension with an expanded polytetrafluoroethylene sheet for congenital ptosis repair can be considered safe and effective and be recommended for clinical use. PMID- 26887687 TI - The medial sural artery perforator flap in intra-oral reconstruction: A Northeast experience. AB - BACKGROUND: The medial sural artery perforator (MSAP) flap is a fasciocutaneous flap that is gaining popularity for intra-oral reconstructions. The aim of this two-centre review was to evaluate the use of the MSAP flap in intra-oral reconstructions and report our experiences. METHODS: Data were collected prospectively on 35 consecutive intra-oral reconstructions using the free MSAP flap. Patient details and intraoperative flap details were recorded. RESULTS: Thirty-five patients underwent intra-oral reconstruction with a free MSAP flap (26 males and nine females). The average flap dimensions were a length of 8.03 cm, a width of 5.0 cm and a thickness of 7.1 mm. Twenty-two flaps had two perforators, and the average pedicle length was 11.1 cm. There were no flap losses. Ninety-one per cent of donor sites were closed primarily. There were two minor complications related to donor-site wound dehiscence, which required delayed skin grafting. The overall complication rate was 5.7%. CONCLUSIONS: The MSAP flap is a good choice for intra-oral reconstruction. It has reliable anatomy and provides thin, pliable skin with a long pedicle. In addition, donor morbidity is low as the donor site can be closed directly in most cases. It is currently our flap of choice for small intra-oral soft tissue defects. PMID- 26887688 TI - Effects of waxy rice starch and short chain amylose (SCA) on the formation of 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system. AB - Starch is a glucose polymer of vast importance to mankind. It forms the major component of all our staple foods. Starch is often used as an important material in cooking meat. In this study, the effects of waxy rice starch and short chain amylose (SCA) from debranched waxy rice starch on the formation of PhIP in a model system were investigated and compared. The results showed that the addition of waxy rice starch and SCA significantly decreased PhIP, and the effect of SCA was more pronounced than that of waxy rice starch. This decrease may be attributed to the fact that the glucose residues of starch condense with the amino group of the creatinine formed N-glycosyl conjugate. This reaction path could disturb the reaction of creatinine with phenylacetaldehyde, subsequently influence the aldol condensation product formation, and finally suppress the formation of PhIP. Furthermore, the complex spatial structure of waxy rice starch disturbs the reaction of the glucosyl hydroxyl groups of glucose with the amino group of creatinine in the model reaction. So the effect of SCA was more pronounced than that of waxy rice starch on suppressing PhIP formation. A possible mechanism of waxy rice starch and SCA for inhibiting PhIP formation in the model system is also proposed. PMID- 26887689 TI - Psychometric Properties of Farsi Version of the Revised Fear Survey Schedule for Children. AB - This study examined the psychometric properties of the Farsi version of the Revised Fear Survey Schedule for Children (Ollendick, 1983), namely the FSSC-FA, in a sample of Iranian children and adolescents (N = 394, 206 girls) aged 9-11:11 years. The internal consistency coefficient was found to range from .79 to .96 for total and subscale scores. The authors used exploratory and confirmatory factor analyses to determine the factor structure of the FSSC-FA. The results showed that a 71-item, six-factor model provided a satisfactory fit for the structure of the FSSC-FA (RMSEA = .07, 90% CIs [.068, .072], CFI = .94, NNFI = .94, chi2/df = 2.94). With regard to gender and age differences in fears of the present sample, girls typically reported more fears than boys (Cohen's d = .28, 95% CIs [.08, .48], p < .001), but differences between older and younger participants were modest. The study also reported most common fears in the sample which were very similar to those reported by other studies except one item being specific to the Iranian population. Bearing in mind the limitations discussed, the results generally show that the FSSC-FA scores are valid and reliable to assess fears in Iranian youth. PMID- 26887691 TI - Questions about aspiration for children with eating, drinking, and swallowing difficulties. PMID- 26887690 TI - Worldwide research productivity in the field of spine surgery: a 10-year bibliometric analysis. AB - PURPOSE: Bibliometrics is increasingly used to assess the quantity and quality of scientific research output in many research fields worldwide. However, the bibliometric studies in the field of spine surgery are scarce. This study aimed to evaluate the worldwide research productivity in the field of spine surgery using bibliometric methods and to provide an insight into the spine research for surgeons and researchers. METHODS: Articles published between 2004 and 2013 were retrieved using the Scopus database in 5 spine journals, including Spine, European Spine Journal, The Spine Journal, Journal of Neurosurgery: Spine, and Journal of Spinal Disorders and Techniques. The number of articles, trend of publications, countries' contribution and h-index, authorship, subspecialty, funding source, journal pattern, institutions, and top cited articles were analyzed. RESULTS: A total of 13,115 publications were identified in the database of Scopus from 2004 to 2013. The time trend of the number of articles showed a significant increase of 1.9-fold between 2004 and 2013 (p = 0.000). The largest number of articles in the field of spine surgery was from United States (39.17%), followed by Japan (10.74%) and China (8.62%). United States also have the highest h-index (106), followed by Canada (60) and United Kingdom (54). China (p = 0.000) and South Korea (p = 0.000) have a significantly increasing trend of contribution proportion to the world spine production over time in years, but h-index was still low (39 and 38, respectively). Spine published the highest number of articles (45.44%), followed by European Spine Journal (21.43%) and Journal of Neurosurgery: Spine (13.32%). The most productive institutions were University of California, San Francisco (1.98%), followed by Thomas Jefferson University (1.61%) and University of Toronto (1.41%). CONCLUSIONS: There has a rapid increase of scientific research productivity in the field of spine surgery during the past 10 years. United States has special contributions to the body of spine publications. China and South Korea have increasing contributions to the field of spine surgery. PMID- 26887692 TI - Quantification of global mitochondrial DNA methylation levels and inverse correlation with age at two CpG sites. AB - Mammalian ageing features biological attrition evident at cellular, genetic and epigenetic levels. Mutation of mitochondrial DNA, and nuclear DNA methylation changes are well established correlates of ageing. The methylation of mitochondrial DNA (mtDNA) is a new and incompletely described phenomenon with unknown biological control and significance. Here we describe the bisulphite sequencing of mtDNA from 82 individuals aged 18-91 years. We detected low and variable levels of mtDNA methylation at 54 of 133 CpG sites interrogated. Regression analysis of methylation levels at two CpG sites (M1215 and M1313) located within the 12S ribosomal RNA gene showed an inverse correlation with subject age suggesting their utility as epigenetic markers of ageing. PMID- 26887693 TI - Expanding the primary health care workforce through contracting with nongovernmental entities: the cases of Bahia and Rio de Janeiro. AB - BACKGROUND: Brazil has experienced difficulties in attracting health professionals (especially doctors and nurses) to practice at the primary health care (PHC) level and in rural and remote areas. This study presents two case studies, each a current initiative in contracting for primary health services in Brazil: one for the state of Bahia and the other for the city of Rio de Janeiro. The two models differ considerably in context, needs, modalities, and outcomes. This article does not attempt to evaluate the initiatives but to identify their strengths and weaknesses. METHODS: Analysis was based on indicators produced by the Brazilian health care information systems, a review of literature and other documentation, and key informant interviews. RESULTS: In the case of Bahia, the state and municipalities decided to create a State Foundation, a new institutional public entity acting under private law that centralizes the hiring of health professionals in order to offer stable positions with career plans and mobility within the state. Results have been mixed as a lower than expected municipal involvement resulted in relatively high administrative costs and consequent default on municipal financial contributions. In the case of Rio de Janeiro, the municipality opted to contract not-for-profit Social Organizations as it made a push to expand access to primary health care in the city. The approach has been successful in expanding coverage, but evidence on cost and performance is weak. CONCLUSIONS: Both cases highlight that improvements in cost and performance data will be critical for meaningful comparative evaluation of delivery arrangements in primary care. Despite the different institutional and implementation arrangements of each model, which make comparison difficult, the analysis provides important lessons for contracting out health professionals for PHC within Brazil and elsewhere. PMID- 26887695 TI - Sex Trafficking of Girls With Intellectual Disabilities: An Exploratory Mixed Methods Study. AB - Few researchers have examined sex trafficking of girls with intellectual disabilities (IDs). Drawing from 54 juvenile sex trafficking (JST) cases, this exploratory, mixed methods study compared 15 JST cases involving girls with ID with 39 JST cases involving girls without ID. Findings revealed a disproportionate risk for exploitation in JST for girls with ID, endangering circumstances creating vulnerability among this population, as well as the perpetrator-victim dynamics that complicate prevention and intervention. Complicating dynamics included victim lack of awareness of exploitation and its endangerments, inability of victims to self-identify, and the relative ease with which traffickers manipulated these girls. The disproportionate risk faced by girls with ID substantiates the need for enhanced safeguards to prevent sexual exploitation of girls with ID including stiffer penalties for those who exploit and buy sex with youth with disabilities. PMID- 26887694 TI - Effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells: dependency on p53 status of tumor cells and types of (10)B-carriers. AB - Purpose To evaluate the effect of oxygen pressure during incubation with a (10)B carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells. Materials and methods Cultured human head and neck squamous cell carcinoma cell line transfected with mutant TP53 (SAS/mp53), or with a neo vector as a control (SAS/neo) was incubated with L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH) as a (10)B-carrier at the (10)B concentration of 60 ppm for 24 h under aerobic (20.7% of oxygen) or hypoxic (0.28% of oxygen) conditions. Immediately after incubation, cultured tumor cells received reactor thermal neutron beams, and a cell survival assay was performed. (10)B concentration of cultured SAS/neo or SAS/mp53 cells incubated under aerobic or hypoxic conditions was determined with a thermal neutron guide tube. Results Hypoxic incubation significantly decreased (10)B concentration of cultured cells with a clearer tendency observed following BPA than BSH treatment in both SAS/neo and SAS/mp53 cells. Following neutron beam irradiation, SAS/mp53 cells showed significantly higher relative biological effectiveness values than SAS/neo cells because of the significantly lower radiosensitivity of SAS/mp53 to gamma-rays than SAS/neo cells. Conclusion Oxygen pressure during incubation with a (10)B carrier had a critical impact on (10)B uptake of cultured tumor cells. PMID- 26887696 TI - Transcultural adaptation and validation of the Celiac Dietary Adherence Test. A simple questionnaire to measure adherence to a gluten-free diet. AB - BACKGROUND AND AIMS: A gluten-free diet is to date the only treatment available to celiac disease sufferers. However, systematic reviews indicate that, depending on the method of evaluation used, only 42% to 91% of patients adhere to the diet strictly. Transculturally adapted tools that evaluate adherence beyond simple self-informed questions or invasive analyses are, therefore, of importance. The aim is to obtain a Spanish transcultural adaption and validation of Leffler's Celiac Dietary Adherence Test. METHODS: A two-stage observational transversal study: translation and back translation by four qualified translators followed by a validation stage in which the questionnaire was administered to 306 celiac disease patients aged between 12 and 72 years and resident in Aragon. Factorial structure, criteria validity and internal consistency were evaluated. RESULTS: The Spanish version maintained the 7 items in a 3-factor structure. Reliability was very high in all the questions answered and the floor and ceiling effects were very low (4.3% and 1%, respectively). The Spearman correlation with the self efficacy and life quality scales and the self-informed question were statistically significant (p < 0.01). According to the questionnaire criteria, adherence was 72.3%. CONCLUSION: The Spanish version of the Celiac Dietary Adherence Test shows appropriate psychometric properties and is, therefore, suitable for studying adherence to a gluten-free diet in clinical and research environments. PMID- 26887697 TI - Evaluating the influence of a fixated object's spatio-temporal properties on gaze control. AB - Despite recent progress in understanding the factors that determine where an observer will eventually look in a scene, we know very little about what determines how an observer decides where he or she will look next. We investigated the potential roles of object-level representations in the direction of subsequent shifts of gaze. In five experiments, we considered whether a fixated object's spatial orientation, implied motion, and perceived animacy affect gaze direction when shifting overt attention to another object. Eye movements directed away from a fixated object were biased in the direction it faced. This effect was not modified by implying a particular direction of inanimate or animate motion. Together, these results suggest that decisions regarding where one should look next are in part determined by the spatial, but not by the implied temporal, properties of the object at the current locus of fixation. PMID- 26887699 TI - Combining nurse-led care with patient self-assessment could enhance tight control of rheumatoid arthritis and management of comorbidities. PMID- 26887698 TI - An approach to quantifying 3D responses of cells to extreme strain. AB - The tissues of hollow organs can routinely stretch up to 2.5 times their length. Although significant pathology can arise if relatively large stretches are sustained, the responses of cells are not known at these levels of sustained strain. A key challenge is presenting cells with a realistic and well-defined three-dimensional (3D) culture environment that can sustain such strains. Here, we describe an in vitro system called microscale, magnetically-actuated synthetic tissues (micro-MASTs) to quantify these responses for cells within a 3D hydrogel matrix. Cellular strain-threshold and saturation behaviors were observed in hydrogel matrix, including strain-dependent proliferation, spreading, polarization, and differentiation, and matrix adhesion retained at strains sufficient for apoptosis. More broadly, the system shows promise for defining and controlling the effects of mechanical environment upon a broad range of cells. PMID- 26887700 TI - Reply: Letter to the editor - A dietary amino acid load causes a transient decrease in the function of human neutrophil granulocytes. PMID- 26887701 TI - Deep-UV nitride-on-silicon microdisk lasers. AB - Deep ultra-violet semiconductor lasers have numerous applications for optical storage and biochemistry. Many strategies based on nitride heterostructures and adapted substrates have been investigated to develop efficient active layers in this spectral range, starting with AlGaN quantum wells on AlN substrates and more recently sapphire and SiC substrates. Here we report an efficient and simple solution relying on binary GaN/AlN quantum wells grown on a thin AlN buffer layer on a silicon substrate. This active region is embedded in microdisk photonic resonators of high quality factors and allows the demonstration of a deep ultra violet microlaser operating at 275 nm at room temperature under optical pumping, with a spontaneous emission coupling factor beta = (4 +/- 2) 10(-4). The ability of the active layer to be released from the silicon substrate and to be grown on silicon-on-insulator substrates opens the way to future developments of nitride nanophotonic platforms on silicon. PMID- 26887702 TI - Re: Health Economic Changes as a Result of Implementation of Targeted Therapy for Metastatic Renal Cell Carcinoma: National Results from DARENCA Study 2. PMID- 26887703 TI - Re: Clinical and Radiographic Predictors of the Need for Inferior Vena Cava Resection during Nephrectomy for Patients with Renal Cell Carcinoma and Caval Tumour Thrombus. PMID- 26887704 TI - Re: Conditional Survival after Radical Cystectomy for Bladder Cancer: Evidence for a Patient Changing Risk Profile over Time. PMID- 26887705 TI - Re: Factors Influencing the Length of Stay after Radical Cystectomy: Implications for Cancer Care and Perioperative Management. PMID- 26887706 TI - Re: Wound Dehiscence in a Sample of 1,776 Cystectomies: Identification of Predictors and Implications for Outcomes. PMID- 26887707 TI - Re: Prostate Biopsy Specimens with Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes. PMID- 26887708 TI - Re: Difference in Association of Obesity with Prostate Cancer Risk between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). PMID- 26887709 TI - Re: Dose-Escalated Irradiation and Overall Survival in Men with Nonmetastatic Prostate Cancer. PMID- 26887710 TI - Re: Apparent Diffusion Coefficient Values of the Benign Central Zone of the Prostate: Comparison with Low- and High-Grade Prostate Cancer. PMID- 26887711 TI - Re: Trends in Testicular Cancer Survival: A Large Population-Based Analysis. PMID- 26887712 TI - Re: Treatment for Metastatic Penile Cancer after First-Line Chemotherapy Failure: Analysis of Response and Survival Outcomes. PMID- 26887713 TI - Re: Clinical Outcomes after Ureteroscopic Lithotripsy in Patients Who Initially Presented with Urosepsis: Matched Pair Comparison with Elective Ureteroscopy. PMID- 26887714 TI - Re: Fibrin Glue Therapy for Severe Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation. PMID- 26887715 TI - Re: Do Kidney Stone Formers Have a Kidney Disease? PMID- 26887716 TI - Re: Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone Formers. PMID- 26887717 TI - Re: Alkali Replacement Raises Urinary Citrate Excretion in Patients with Topiramate-Induced Hypocitraturia. PMID- 26887718 TI - Re: EAU Guidelines on Interventional Treatment for Urolithiasis. PMID- 26887719 TI - Re: Initial Experience and Comparative Efficacy of the UreTron: A New Intracorporeal Ultrasonic Lithotriptor. PMID- 26887721 TI - Re: Artificial Urinary Sphincter Outcomes in the "Fragile Urethra". PMID- 26887720 TI - Re: Practice Patterns in the Treatment of Urethral Stricture among American Urologists: A Paradigm Change? PMID- 26887722 TI - Re: American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. PMID- 26887723 TI - Re: Utilities of Split-Thickness Skin Grafting for Male Genital Reconstruction. PMID- 26887724 TI - Re: Alternative Medications for Medications in the Use of High-Risk Medications in the Elderly and Potentially Harmful Drug-Disease Interactions in the Elderly Quality Measures. PMID- 26887725 TI - Re: How to Use the American Geriatrics Society 2015 Beers Criteria-A Guide for Patients, Clinicians, Health Systems, and Payors. PMID- 26887726 TI - Re: Factors Influencing Deprescribing Habits among Geriatricians. PMID- 26887727 TI - Re: Urinary Retention Rates after Intravesical OnabotulinumtoxinA Injection for Idiopathic Overactive Bladder in Clinical Practice and Predictors of this Outcome. PMID- 26887728 TI - Re: Traumatic Spinal Cord Injury in the United States, 1993-2012. PMID- 26887729 TI - Re: Intermittent Catheterisation for Long-Term Bladder Management (Abridged Cochrane Review). PMID- 26887730 TI - Re: Adjustable Continence Balloons in Men: Adjustments Do Not Translate into Long Term Continence. PMID- 26887731 TI - Re: Quality of Life in Women Who Use Pessaries for Longer than 12 Months. PMID- 26887732 TI - Re: Removal or Revision of Vaginal Mesh Used for the Treatment of Stress Urinary Incontinence. PMID- 26887733 TI - Re: Physician Use of Sacral Neuromodulation among Medicare Beneficiaries with Overactive Bladder and Urinary Retention. PMID- 26887734 TI - Re: The Role of Inflammation in Lower Urinary Tract Symptoms (LUTS) due to Benign Prostatic Hyperplasia (BPH) and its Potential Impact on Medical Therapy. PMID- 26887735 TI - Re: Improvement of Lower Urinary Tract Symptoms and Sexual Activity after Open Simple Prostatectomy: Prospective Analysis of 50 Cases. PMID- 26887736 TI - Re: The Impact of Abdominal Aortic Calcification and Visceral Fat Obesity on Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia. PMID- 26887737 TI - Re: Impact of 120-W 2-MUm Continuous Wave Laser Vapoenucleation of the Prostate on Sexual Function. PMID- 26887738 TI - Re: Genetic Testing in the Assessment of Living Related Kidney Donors at Risk of Autosomal Dominant Polycystic Kidney Disease. PMID- 26887739 TI - Re: Transplanting Kidneys from Deceased Donors with Severe Acute Kidney Injury. PMID- 26887740 TI - Re: Use of Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction and Risk of Malignant Melanoma. PMID- 26887741 TI - Re: Unexpected Long-Term Improvements in Urinary and Erectile Function in a Large Cohort of Men with Self-Reported Outcomes following Radical Prostatectomy. PMID- 26887742 TI - Re: The Safety and Efficacy of Clomiphene Citrate in Hypoandrogenic and Subfertile Men. PMID- 26887743 TI - Re: Erectile Dysfunction in 1050 Men following Extended (18 Cores) vs Saturation (28 Cores) vs Saturation plus MRI-Targeted Prostate Biopsy (32 Cores). PMID- 26887745 TI - Re: Effect of Sexual Diary Keeping and Self-Evaluation on Female Sexual Function and Depression: A Pilot Study. PMID- 26887744 TI - Re: How Successful is TESE-ICSI in Couples with Non-Obstructive Azoospermia? PMID- 26887746 TI - Re: Vasectomy Reversal for Postvasectomy Pain Syndrome: A Study and Literature Review. PMID- 26887747 TI - Re: Assessment of Time-Dependent Changes in Semen Parameters in Infertile Men after Microsurgical Varicocelectomy. PMID- 26887748 TI - Re: Differences in the Seminal Plasma Proteome are Associated with Oxidative Stress Levels in Men with Normal Semen Parameters. PMID- 26887749 TI - Re: Male Biological Clock: A Critical Analysis of Advanced Paternal Age. PMID- 26887750 TI - Re: Hymenal Anomalies in Twins-Review of the Literature and Case Report. PMID- 26887751 TI - Re: Combined Creatinine Velocity and Nadir Creatinine: A Reliable Predictor of Renal Outcome in Neonatally Diagnosed Posterior Urethral Valves. PMID- 26887752 TI - Re: Higher Incidence of Hypospadias in Monochorionic Twins. PMID- 26887754 TI - Re: Prevalence, Repairs and Complications of Hypospadias: An Australian Population-Based Study. PMID- 26887753 TI - Re: Further Analysis of the Glans-Urethral Meatus-Shaft (GMS) Hypospadias Score: Correlation with Postoperative Complications. PMID- 26887755 TI - Re: Expression of Nuclear Matrix Proteins Binding Matrix Attachment Regions in Prostate Cancer. PARP-1: New Player in Tumor Progression. PMID- 26887756 TI - Re: Prostate Sphere-Forming Stem Cells are Derived from the P63-Expressing Basal Compartment. PMID- 26887757 TI - Re: Chronic Oxidative Stress Leads to Malignant Transformation Along with Acquisition of Stem Cell Characteristics, and Epithelial to Mesenchymal Transition in Human Renal Epithelial Cells. PMID- 26887758 TI - Optimizing the post-graduate institutional program evaluation process. AB - BACKGROUND: Reviewing program educational efforts is an important component of postgraduate medical education program accreditation. The post-graduate review process has evolved over time to include centralized oversight based on accreditation standards. The institutional review process and the impact on participating faculty are topics not well described in the literature. METHODS: We conducted multiple Plan-Do-Study-Act (PDSA) cycles to identify and implement areas for change to improve productivity in our institutional program review committee. We also conducted one focus group and six in-person interviews with 18 committee members to explore their perspectives on the committee's evolution. One author (MLL) reviewed the transcripts and performed the initial thematic coding with a PhD level research associate and identified and categorized themes. These themes were confirmed by all participating committee members upon review of a detailed summary. Emergent themes were triangulated with the University of Michigan Medical School's Admissions Executive Committee (AEC). RESULTS: We present an overview of adopted new practices to the educational program evaluation process at the University of Michigan Health System that includes standardization of meetings, inclusion of resident members, development of area content experts, solicitation of committed committee members, transition from paper to electronic committee materials, and focus on continuous improvement. Faculty and resident committee members identified multiple improvement areas including the ability to provide high quality reviews of training programs, personal and professional development, and improved feedback from program trainees. CONCLUSIONS: A standing committee that utilizes the expertise of a group of committed faculty members and which includes formal resident membership has significant advantages over ad hoc or other organizational structures for program evaluation committees. PMID- 26887759 TI - Gaucher's Disease with Cardiac Valve Calcification and Stenosis: A Rare Presentation due to Homozygous p.D409H Mutation in a North Indian Family. PMID- 26887760 TI - Field Testing of Appropriate Technological Tool of Individualised Color Coded Any Day Neonatal Growth Monitoring Charts for Neonatal Care at Primary Health Care Level. AB - OBJECTIVE: To field test the Individualised Color Coded Any Day (ICCAD) growth monitoring charts at primary health care level in three districts of Maharashtra. METHODS: The present study was conducted in three districts of Maharashtra - Pune, Satara and Kolhapur and included newborns with weight >= 1500 g born during 1st May 2010 to 30th July 2011. Talukas were matched based on mortality and coverage indicators and put in study (ICCAD use) and control area (ICCAD non-use) from every District. Health centres were selected from each taluka where facilities of expert obstetric and pediatric services did not exist but number of deliveries conducted was high. Data was collected during neonatal period. Three patterns of ICCAD charts; 1500 g to 1999 g, 2000 to 2499 g and >=2500 g; developed from daily weight record of 430 newborns for 30 d were used. Outcome measures were neonatal mortality rate (NMR) and weight gain in study and control groups. RESULTS: There were 6705 live births from study and 6341 from control area. The NMR of study area (6.3/1000 live births) was significantly lesser as compared to control area (10.6/1000 live births). Birth weight group specific NMR of birth weight between 1500 to <2000 g and >=2500 g was significantly lower in study area as compared to control area. There was improvement in mean gain weight of 15 g, 43 g and 89 g for respective birth weight groups in ascending order. CONCLUSIONS: This innovative appropriate technological tool based on translational research of ICCAD neonatal growth monitoring charts appears to have benefited the decision of type of care. PMID- 26887761 TI - Role of Dentists in Managing Pediatric Celiac Disease. PMID- 26887763 TI - Egyptian doctors vote for free hospital care in police assault protest. PMID- 26887762 TI - Clinical Abacavir Hypersensitivity Reaction among Children in India. AB - Abacavir is currently recommended as a part of first line regimen by National AIDS Control Organization. The objective of this study was to observe the incidence of clinically diagnosed abacavir Hypersensitivity reaction (HSR) among children on abacavir based therapy in the National program. In this observational study, all children started on abacavir were included and HSR reaction was diagnosed clinically as per National guidelines. HLA- B*5701 testing was done in children diagnosed with clinical abacavir HSR. Among 101 children started on abacavir during the study period, 8 [7.9 % (95 % CI 3.5-15.0 %)] children developed clinically diagnosed abacavir HSR. All children with concomitant illness (4/8) were HLA-B*5701 negative. Only 2 (25 %, 2/8) carried HLA-B*5701 allele. Fever with abdominal symptoms as compared to respiratory symptoms were more common in HLA-B*5701 positive cases. Overdiagnosis of clinically diagnosed abacavir HSR is common and could be decreased by treating concomitant illness before starting abacavir. PMID- 26887764 TI - [Consensus on diagnosis and treatment of hyperemesis gravidurum (2015)]. PMID- 26887765 TI - [Using of gonadotropin releasing hormone antagonist protocol: a committee opinion]. PMID- 26887766 TI - [The multidisciplinary and long-term management of polycystic ovary syndrome]. PMID- 26887767 TI - [A case-control study of correlation between serum adiponectin levels and polycystic ovary syndrome]. AB - OBJECTIVE: To compare the difference of serum adiponectin levels between polycystic ovary syndrome (PCOS) patients and age, boby mass index (BMI) and insulin-resistance index matched controls, and explore its influence factors. METHODS: Case-control study, involving 97 women with PCOS and 116 age, BMI, fasting plasma glucose and insulin levels, homeostasis model assessment-insulin resistance index (HOMA-IR) matched controls. Hormone profiles, and serum adiponectin levels were measured and compared. Hormone profiles and serum adiponectin levels were compared among the four PCOS phenotypes. Multiple regression analysis was used to evaluate the factors affecting serum adiponectin levels. RESULTS: (1) Serum adiponectin level was significantly lower in PCOS group [(21+/-16) mg/L] than controls [(25+/-13) mg/L, P=0.038], and the same result in stratified analysis on weight height ratio (WHR, >=0.8 and <0.8). (2) There was statistical differences in testosterone among different four PCOS phenotypes (P=0.001), there were no statistical differences in FSH, LH, WHR and serum adiponectin levels among four PCOS phenotypes (P>0.05). (3) WHR and PCOS status were independent determinants of serum adiponectin levels (P<0.05). CONCLUSIONS: Low serum adiponectin levels in the women with PCOS is correlated with PCOS per se, independent of insulin resistance and obese. This fact supports the further study of the effect of adiponection in the pathophysiology of PCOS and its log-term impact. PMID- 26887768 TI - [A pilot study of serum anti-Mullerian hormone in diagnosis of polycystic ovary syndrome based on 2012 Chinese polycystic ovary syndrome diagnosis criteria]. AB - OBJECTIVE: Based on 2012 Chinese polycystic ovary syndrome (PCOS) diagnosis criteria, we detect the serum anti-Mullerian hormone (AMH) levels in PCOS patients, to evaluate the diagnosis value of AMH for PCOS. METHODS: Totally 217 PCOS patients were chosen as study group and 204 non-PCOS women were as controls. Their clinical information (body weight, score for acne and hirsutism), ultrasonography for ovarian volume and the number of small follicle, and blood sample detected for hormonal and metabolic parameters were obtained. Spearman's analysis and the receiver operating characteristic curve (ROC curve) were used to assess relevance and the diagnostic efficiency of AMH in PCOS. RESULTS: Serum AMH level was significantly higher in PCOS group compared with the control group (105.46 versus 26.28 pmol/L, P<0.01). Serum AMH were positively related to Ferriman and Gallwey (F-G) score (r=0.526, P<0.01), global acne grading system (GAGS) score (r=0.359, P<0.01), total testosterone (r=0.514, P<0.01), LH/FSH ratio (r=0.542, P<0.01), fasting plasma glucose (r=0.373, P<0.01), fasting insulin (r=0.168, P=0.008), homeostasis model assessment for insulin resistance (HOMA-IR) index (r=0.182, P=0.004), total cholesterol (r=0.247, P<0.01), triglyceride (r=0.235, P<0.01), total ovarian volume (r=0.204, P=0.008), and mean number of small follicle (r=0.693, P<0.01). The area under the ROC curve for PCOS diagnosed by AMH was 0.954 (P<0.01). the threshold of AMH for PCOS diagnosis was 57.76 pmol/L, diagnostic efficiency was high (sensitivity 95.1%, specificity 89.3%). CONCLUSION: Based on 2012 Chinese PCOS diagnosis criteria, serum AMH level elevated in PCOS, and correlated with women's hormonal imbalance and abnormal follicular development. PMID- 26887769 TI - [Case-control based study between polymorphisms in the adiponectin gene and polycystic ovary syndrome]. AB - OBJECTIVE: To investigate the frequeney of four single nucleotide polymorphism (SNP) sites (rs17300539, rs12495941, rs2241766 and rs1501299) of adiponectin gene (ADIPOQ) and to elucidate its role in the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: A total of 207 women with PCOS and 192 controls were recruited. Four ml whole-blood samples were collected in tubes containing ethylene diamine tetraacetic acid (EDTA) by peripheral venous puncture. Genomic DNA was extracted using a QIAamp DNA mini kit. Four SNP sites (rs17300539, rs12495941, rs2241766 and rs1501299) of ADIPOQ were amplified by PCR and then directly sequenced to screen variants. RESULTS: (1) The genotype frequencies of AA of rs17300539 in PCOS was significantly higher than controls [57.5% (119/207) versus 48.4% (93/192), P<0.05]. The genotype frequencies of AA of rs1501299 in PCOS was significantly lower than controls [4.8% (10/207) versus 11.5% (22/192), P<0.05]. While no significant differences were found in rs2241766 and rs12495941 (P>0.05). (2) The allele A of rs17300539 [75.8% (314/414)] and allele C frequeneies of rs1501299 [76.3% (316/414)] in PCOS were significantly higher than controls [67.7% (260/384), 69.0% (265/384), respectively; all P<0.05]. While no significant differences were found in rs2241766 and rs12495941 (P>0.05). (3) Further analysis we found rs17300539 AA genotypes had an increased risk for PCOS compared with GG genotype (OR=2.670, P=0.009), rs1501299 CC genotype had an increased risk for PCOS compared with AA genotypes (OR=2.756, P=0.012); and the difference remained significantly after adjustment for age, testosterone and body mass index (P<0.05). CONCLUSIONS: No significant differences were observed in genotype and allele frequencies between PCOS and controls for rs2241766 and rs12495941. However, we observed an association between rs17300539, rs1501299 and PCOS. rs17300539 and rs1501299 of ADIPOQ perhaps are the susceptibility gene locus of PCOS. PMID- 26887770 TI - [Characteristics of oral glucose tolerance test in 9803 pregnant women of different pre-pregnancy body mass index and its relationship with the incidence of gestational diabetes mellitus]. AB - OBJECTIVE: To investigate the values and characteristics of 75 g oral glucose tolerance test (OGTT) in women with different pre-pregnancy body mass index (BMI) and to evaluate the risk of gestational diabetes mellitus (GDM). METHODS: Medical records of 9803 pregnant women attending the Peking University First Hospital and delivered between July 1, 2011 and December 31, 2013 were retrospectively analyzed. The frequency of adverse pregnancy outcomes across different degrees pre-pregnancy BMI was calculated. We divided participants into 4 groups based on pre-pregnancy BMI, underweight: BMI<18.5 kg/m(2) (1221 cases), normal weight: 18.5-23.9 kg/m(2) (6594 cases), overweight: 24-27.9 kg/m(2) (1549 cases), obesity: >=28.0 kg/m(2) (439 cases). The diagnosis of GDM was made when any one of the values was met or exceeded in 75 g OGTT. The characteristics of 75 g OGTT and the incidence of GDM were analyzed. RESULTS: (1) The average age, pre pregnancy weight, height and pre-pregnancy BMI of the participants was (30.5+/ 3.7) years, (57.7+/-9.0) kg, (162.8+/-4.9) cm and (21.8+/-3.2) kg/m(2), respectively. All the values of 75 g OGTT were presented normal distribution. (2) There was statistical difference in the glucose levels among women with different pre-pregnancy BMI. The fasting, 1-hour, 2-hour glucose were (4.55+/-0.34), (7.31+/-1.54), (6.38+/-1.23) mmol/L in underweight women, (4.65+/-0.38), (7.70+/ 1.59), (6.70+/-1.27) mmol/L in normal weight women, (4.82+/-0.47), (8.29+/-1.67), (7.04+/-1.29) mmol/L in overweight women and (4.94+/-0.48), (8.56+/-1.64), (7.10+/-1.35) mmol/L in obesity women (P<0.01). (3) The incidence of GDM was 21.76% (2133/9803) in our study. There were 1374 cases (64.42%, 1374/2133) with only one abnormal OGTT value while 759 cases (35.58%, 759/2133) with two or more abnormal values. The incidence of GDM in women with underweight, normal weight, overweight and obesity was 12.53% (153/1221), 19.71% (1300/6594), 32.73% (507/1549) and 39.41% (173/439), respectively (P<0.05). Meanwhile, the incidence of women with two and more abnormal OGTT value in GDM was increased as the pre pregnancy increasing. CONCLUSION: The risk of GDM is increased as pre-pregnancy BMI increasing, and the risk of GDM increases significantly in women with pre pregnancy overweight or obesity. PMID- 26887771 TI - [Expression of glucose regulated protein 78 and the pathogenesis of gestational diabetes mellitus]. AB - OBJECTIVE: To investigate the relationship between the expression of glucose regulated protein 78 (GRP78) in the placental trophoblast cells and the pathogenesis of gestational diabetes mellitus (GDM). METHODS: All the patients were recruited from Qingdao Municipal Hospital from May 2013 to May 2014. Among them, fifty women with GDM were assigned to the GDM group, and fifty healthy women were defined as the control group. All of them received cesarean section because of breech presentation, contracted pelvis, scarred uterus or on mother's demand. Real-time PCR was conducted to analyze the expression of GRP78 mRNA in the trophoblasts. Immunohistochemistry was performed to detect the localization of GRP78 protein in the placentasl trophoblast cells. RESULTS: (1) GRP78 mRNA expressed in the cytoplasm of trophoblasts of both the GDM group and the control group. The GRP78 mRNA levels in the GDM group and the control group were 15.6+/ 0.4 and 6.0+/-0.7, respectively. The relative expression level of GRP78 mRNA in the GDM group was 2.6 times of that in the control group, with statistically significant difference (P<0.01). (2) The expression of GRP78 protein was found in the cytoplasm of the trophoblasts of the GDM group. It showed in deep, light brown or yellow after staining, according to the expression degree. The expression of GRP78 protein was also found in the cytoplasm of the trophoblasts of the control group, but it mainly showed yellow color (38/50). The strong positive rate of GRP78 protein in the GDM group (96%, 48/50) was higher than that in the control group (22%, 11/50; P<0.01). CONCLUSION: The expression of GRP78 increased in the placental trophoblast cells of GDM patients. It might suggest that GRP78 had some effect on the pathogenesis of GDM. PMID- 26887772 TI - [Ovarian clear cell carcinoma derived from endometriotic cyst: a clinicopathological analysis of 54 cases]. AB - OBJECTIVE: To clarify the clinicopathological features of ovarian clear cell carcinoma derived from endometriotic cyst (EC-OCCC). METHODS: Totally 54 cases of EC-OCCC were recruited in the current retrospective study. The relation between ages, clinical symptoms and signs, surgical and pathological stages, serum CA125, findings of ultrasound, treatments and the sites of tumors, macro- and micro features and expression of immunostainings were analyzed. RESULTS: (1) Clinical features: the ages of patients were (50+/-6) years old (range 31-62 years old). Pelvic mass was the major complaint of 50 patients (93% , 50/54). Forty-five cases belonged to International federation of Gynecology and Obstetrics (FIGO) stage I, 4 cases were stage II and another 5 cases were stage III. Serum CA125 was elevated in 21 cases (54%, 21/39) before therapy. Doppler ultrasound showed 46 cases (85%, 46/54) had solid masses in pelvis. (2) Pathological findings: 52 cases (96%, 52/54) had their tumor unilaterally, and 2 cases (4%, 2/54) occurred bilaterally. The maximal diameters of endometriotic cyst (EC) ranged from 1.5 to 23.0 cm and maximal diameters of ovarian clear cell carcinoma (OCCC) components were from 0.5 to 12.0 cm. Fifty-one cases (94%, 51/54) had their tumor within EC, which showed focally irregular protrudings, grey-white papillae or solid nodules attached to the cyst wall. Three cases (6%, 3/54) appeared as irregular thickened wall of the cysts, ranged from 1.5 to 6.0 cm in the maximal length, with the microscopic features of EC and OCCC and the transitional areas between the 2 morphologies. All cases expressed cytokeratin (CK) 7 and pan-CK AE1/AE3, 17 cases (33%, 17/51) expressed ER and 5 cases (10%, 5/51) expressed PR. TP53 showed mutational phenotype in 19 cases (36%, 19/53). Sixteen cases (30%, 16/54) combined with uterine adenomyosis and 25 cases (46%, 25/54) with endometriosis at other sites. (3) Survival survey: during the period of 39.1 months follow-up, 3 cases relapsed and 2 cases died. (4) There was a significant difference of serum CA125 between patients of early-and advanced-stages (P=0.049). There were no differences identified in ages, diameters of EC and OCCC, the expression level of ER, PR and TP53, the co-existence of adenomyosis and endometrosis, as well as ultrasonic findings (P>0.05). CONCLUSION: EC-OCCC could be recognized in early stage by symptoms and ultrasound due to accompanied endometriotic cysts, resulting in relatively good prognosis. PMID- 26887773 TI - [Response of potassium channels to estrogen and progesterone in the uterine smooth muscle cells of adenomyosis in vitro]. AB - OBJECTIVE: To investigate the expression of potassium channels and the influence of estrogen and progesterone on the cultured uterine smooth muscle cells (USMC) of adenomyosis in vitro. METHODS: There were 22 cases of adenomyosis hysterectomy in the adenomyosis group and 12 patients with cervical intraepithelial neoplasia III removal of the uterus in the control group. USMC were separated and cultured in vitro, incubated with different concentrations of estrogen and progesterone. We used reverse transcription-PCR to dectect the expression of large-conductance calcium- and voltage-sensitive potassium channel alpha subunit (BKCa alpha) and voltage-gated potassium channel 4.3 (Kv4.3). RESULTS: The mRNA expression of BKCa alpha and Kv4.3 in the adenomyosis group (4.43+/-2.05 and 4.52+/-1.97) were significantly higher than those in the control group (0.83+/-0.25 and 0.86+/ 0.19, P<0.05). In the control group, Kv4.3 mRNA decreased after treated with 0.1 nmol/L (0.17+/-0.10) and 1.0 nmol/L (0.13+/-0.08) estrogen than before (0.55+/ 0.29, P<0.05). In the adenomyosis group, BKCa alpha mRNA decreased significantly after treated with 10.0 nmol/L estrogen (0.56+/-0.27 versus 1.01+/-0.35, P<0.05). 0.1 umol/L progesterone elevated both BKCa alpha mRNA (0.44+/-0.24 versus 0.16+/ 0.09) and Kv4.3 mRNA (1.29+/-0.51 versus 0.55+/-0.29) in the control group (all P<0.05); however, there were no significant difference in adenomyosis group of different concentration of progestrone (P>0.05). CONCLUSION: There is an abnormal expression of potassium channels in the adenomyosis USMC, which is regulated by high concentration of estrogen and might be resistant to progesterone. PMID- 26887774 TI - [Effect of glucose regulated protein 78 on autophagy and apoptosis in ovarian epithelial carcinoma]. AB - OBJECTIVE: To explore the effect and mechanism of glucose regulated protein 78 (GRP78) on autophagy and apoptosis in ovarian carcinoma, and to investigate the influence on the growth and sensitivity to cisplatin on the ovarian cancer cells. METHODS: The human ovarian cancer cell line SKOV3 were treated by the GRP78 regulator BAPTA-AM and A23187, which were used to decrease or increase the expression levels of GRP78, respectively. The experiment were divided into three groups. Cells in the group of BAPTA-AM were treated by BAPTA-AM at the final concerntration of 40 umol/L for 1 hour. Cells in the group of A23187 were treated by A23187 at the final concerntration of 4 umol/L for 24 hours. While, cells in the control group were treated by culture medium without any GRP78 regulator for 24 hours. The expressions of GRP78, beclin1, Bcl-2 and CHOP mRNA and protein were detected by reverse transcription (RT)-PCR and western blot. The autophagy levels was observed by green fluorescent protein-microtubule-associated protein 1 light chain 3-II (GFP-LC3-II) fluorescence staining. The flow cytometry was used to analyse the apoptosis rates of cells. The effect on cell growth and the sensitivity to cisplatin of SKOV3 were accessed by methyl thiazolyl tetrazolium (MTT). RESULTS: (1) The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of BAPTA-AM were 0.583+/-0.025, 0.860+/-0.055, 0.714+/-0.032 and 0.811+/ 0.004, respectively. The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of A23187 were 0.840+/-0.044, 0.654+/-0.065, 0.908+/-0.047 and 0.620+/ 0.062, respectively. The mRNA expressions of GRP78, beclin1, Bcl-2 and CHOP in the control group were 0.687+/-0.032, 0.772+/-0.029, 0.845+/-0.018, 0.712+/ 0.077, respectively. While the protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of BAPTA-AM were 0.423+/-0.035, 0.952+/-0.022, 0.385+/-0.032, 0.681+/-0.095, respectively. The protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the group of A23187 were 0.743+/-0.032, 0.638+/-0.025, 0.596+/-0.029, 0.431+/-0.095, respectively. The protein expressions of GRP78, beclin1, Bcl-2 and CHOP in the control group were 0.617+/-0.031, 0.789+/-0.083, 0.492+/-0.036, 0.531+/-0.003, respectively. The mRNA and protein expressions of beclin and CHOP in the group of BAPTA-AM were both higher than those in the control group (P<0.05). While, the mRNA and protein expressions of beclin and CHOP in the group of A23187 were both lower than those in the control group (P< 0.05). (2) The autophagy fluorescence of SKOV3 in the group of BAPTA-AM, A23187 and the control group were 706+/-117, 473+/-128, 595+/-126, respectively, in which there were significant differences among three groups (P<0.05). (3) The apoptosis rate of SKOV3 in the group of BAPTA-AM was (27.4+/-2.2)%, which was higher than that in the control group [(19.6+/-1.4)%, P<0.05]. The apoptosis rate of SKOV3 in the group of A23187 was (12.2+/-1.9)%, which was lower than that in the control group (P<0.05). (4) The comparison of the sensitivity to cisplatin in 3 groups of SKOV3. The 50% inhibition concentration (IC50) of SKOV3 to cisplatin was (3.02+/ 0.62) mg/L. After treated by BAPTA-AM + cisplatin, the IC50 was (2.00+/-0.17) mg/L and the sensitivity of SKOV3 to cisplatin was increased by 33.8%, and there was significant difference (P<0.05), compared with the control group. And after treated by A23187 + cisplatin, the IC50 was (4.91+/-2.52) mg/L and the sensitivity of SKOV3 to cisplatin was decreasd by 62.6%; and there was significant difference (P<0.05), compared with the control group. CONCLUSION: GRP78 could regulate autophagy and apoptosis of ovarian cancer cells by regulating the expressions of beclin1, Bcl-2 and CHOP, thereby affecting the sensitivity to cisplatin in ovarian carcinoma, which may be a new method for the treatment and improvement of the sensitivity to cisplatin in ovarian carcinoma. PMID- 26887775 TI - [Cisplatin resistant effects of dihydrofolate reductase gene expression up regulation in epithelial ovarian cancer]. AB - OBJECTIVE: To investigate the effects of dihydrofolate reductase (DHFR) gene expression up-regulating on cisplatin resistance in epithelial ovarian cancer cell lines. METHODS: The cDNA length of DHFR gene was amplified by PCR and was connected to lentiviral vector pWPI, the recombinant retroviral vector DHFR-pWPI was infected SKOV3 cells by lipofectamine 2000. The groups included DHFR-pWPI SKOV3 cell, pWPI-SKOV3 cell and SKOV3 cell group. Western blot was used to detect the expression of DHFR. Flow cytometry was applied to measure the cell apoptosis rate of 3 groups cells in different cisplatin concentrations (2.5, 5.0, 10.0, 20.0 ug/ml) and at different time period (24, 48 and 72 hours), and half maximal inhibitory concentration (IC50) treated with cisplatin concentration (6.0, 4.0, 4.9 ug/ml). High performance liquid chromatography (HPLC) was applied to test intracellular cisplatin concentration in different cisplatin concentration (4.0, 6.0, 8.0 ug/ml) at 24 and 48 hours. Transmission electron microscope was used to observe ultrastructural changes cells under IC50 cisplatin concentration. RESULTS: The recombinant plasmid DHFR-pWPI was constructed and then infected into SKOV3 cell successfully. (1) The expression of DHFR detected by western blot in transfection group was higher than those in the negative control group and blank control group (10.280+/-0.009 vs 2.050+/-0.003 vs 3.480+/-0.003; P<0.01). (2) Treated with cisplatin concentration (2.5, 5.0, 10.0, 20.0 ug/ml) at 24, 48 hours, the apoptosis rate detected by flow cytometry results shown that they were lower than those in the negative control group and blank control group (P<0.05), while treated at the concentration of 5.0 and 10.0 ug/ml for 72 hours, whose apoptosis rate in transfection group was higher than those in the negative control group and blank control group (P<0.05). When treated cells under IC50 cisplatin concentration (6.0, 4.0, 4.9 ug/ml) at for 24 and 48 hours, the results indicated that there were mainly G0/G1 stage cell cycle rate in 3 groups, it was obviously higher in transfection group than those in two control groups (P<0.05). However, mainly G2/M, S stage cell cycle rate for 72 hours, and S stage cell cycle rate in transfection group obviously higher than those in two control groups, but G2/M stage cell cycle rate were lower (P<0.01). (3) After treated with cisplatin concentration (4.0 ug/ml) for 24, 48 hours and cisplatin concentration (6.0 ug/ml) for 24 hours, the intracellular cisplatin content tested by HPLC method in the transfection group were significantly lower than those in two control groups (P<0.01). While, at 6.0 ug/ml of cisplatin concentration for 48 hours and 8.0 ug/ml of cisplatin concentration for 24 and 48 hours, the intracellular cisplatin content of transfection group were obviously higher than those two control groups (P<0.05). (4) Treated with IC50 (6.0, 4.0, 4.9 ug/ml) cisplatin concentration at different time to obeserve ultrastructural changes by transmission electron microscopy. The results shown that the microwire gathered together at 24 and 48 hours, and the number and structure of mitochondria had obvious change in transfection group, while there was rare microfilament, the number of mitochondria decreased but structure change was not apparent in two control groups. There were appeared expansion of endoplasmic reticulum and had rare normal organelles among three groups. After treated with cisplatin for 72 hours, there were inordinate microfilament, a part of nuclear membrane disappeared, a lot of ribosomes gathered together in two control groups, and there were rare microfilament in transfection group, nuclear membrane completely disappeared, many white cystic matter were seen in cytoplasm, mitochondrial structure disappeared completely, which seems most cells on the verge of death. CONCLUSION: The lentiviral expressing vector harboring human DHFR gene were successfully constructed. When the up- expression of DHFR gene, the drug-resistant in ovarian cancer cell may be increase, which suggest that there were certain contact between resistance increases with microfilament gathered and the change of the mitochondria. PMID- 26887776 TI - Genetic differences between paediatric and adult Burkitt lymphomas. AB - Dysregulation of MYC is the genetic hallmark of Burkitt lymphoma (BL) but it is encountered in other aggressive mature B-cell lymphomas. MYC dysregulation needs other cooperating events for BL development. We aimed to characterize these events and assess the differences between adult and paediatric BLs that may explain the different outcomes in these two populations. We analysed patterns of genetic aberrations in a series of 24 BLs: 11 adults and 13 children. We looked for genomic imbalances (copy number variations), copy-neutral loss of heterozygosity (CN-LOH) and mutations in TP53, CDKN2A, ID3 (exon 1), TCF3 (exon17) and CCND3 (exon 6). Young patients displayed more frequent 13q31.3q32.1 amplification, 7q32q36 gain and 5q23.3 CN-LOH, while 17p13 and 18q21.3 CN-LOH were only detected in adult BLs. ID3 mutations were present in all adult samples, but only in 42% of childhood cases. CCND3 and ID3 double-hit mutations, as well as 18q21 CN-LOH, seemed to be associated with poorer outcome. For the first time, we report different genetic anomalies between adult and paediatric BLs, suggesting age-related heterogeneity in Burkitt lymphomagenesis. This may explain the poorer prognosis of adult BLs. Additional studies are needed to confirm these results in the setting of clinical trials. PMID- 26887778 TI - Regulation of nonadiabatic processes in the photolysis of some carbonyl compounds. AB - Carbonyl compounds studied are confined to acetyl halide (CH3COCl), acetyl cyanide (CH3COCN), acetyl sulfide (CH3COSH), acetaldehyde (CH3CHO), and methyl formate (HCOOCH3). They are asymmetrically substituted, but do not follow the well-known Norrish type I reactions. Each compound ejected in an effusive beam at about 300 K is commonly excited to the (1)(n, pi*)CO lower state; that is, a nonbonding electron on O of the C[double bond, length as m-dash]O group is promoted to the antibonding orbital of pi*CO. The photolysis experiments are conducted in the presence of Ar gas and the corresponding fragments are detected using time-resolved Fourier-transform Infrared (FTIR) emission spectroscopy. The enhancement of the collision-induced internal conversion or intersystem crossing facilitates the dissociation channels via highly vibrational states of the ground singlet (So) or triplet (T1) potential energy surfaces. In this manner, an alternative nonadiabatic channel is likely to open yielding different products, even if the diabatic coupling strength is strong between the excited state and the neighboring state. For instance, the photodissociation of CH3COCl at 248 nm produces HCl, CO, and CH2 fragments, in contrast to the supersonic jet experiments showing dominance of the Cl fragment eliminated from the excited state. If the diabatic coupling strength is weak, dissociation proceeds mainly through internal conversion, such as the cases of CH3COCN and CH3COSH. The photodissociation of CH3COCN at 308 nm has never been reported before, while for CH3COSH matrix-isolated photodissociation was conducted that shows a distinct spectral feature from the current FTIR method. The CH3CHO and HCOOCH3 molecules belong to the same type of carbonyl compounds, in which the molecular products, CO + CH4 and CO + CH3OH, are produced through both transition state and roaming pathways. Their products are characterized differently between molecular beam and current FTIR experiments. For instance, the photodissociation of HCOOCH3 at 248 nm yields CO with the vibrational state v >= 4, in contrast to the molecular beam experiments producing CO at v = 1. The photodissociation of CH3CHO at 308 nm intensifies a low energy component in the CH4 vibrational distribution, thus verifying the transition state pathway for the first time. PMID- 26887780 TI - Alcohol and serious harms of antidepressant treatment. PMID- 26887777 TI - Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse. AB - Accumulating evidence suggests significant biological effects caused by extremely low frequency electromagnetic fields (ELF-EMF). Although exo-endocytosis plays crucial physical and biological roles in neuronal communication, studies on how ELF-EMF regulates this process are scarce. By directly measuring calcium currents and membrane capacitance at a large mammalian central nervous synapse, the calyx of Held, we report for the first time that ELF-EMF critically affects synaptic transmission and plasticity. Exposure to ELF-EMF for 8 to 10 days dramatically increases the calcium influx upon stimulation and facilitates all forms of vesicle endocytosis, including slow and rapid endocytosis, endocytosis overshoot and bulk endocytosis, but does not affect the RRP size and exocytosis. Exposure to ELF-EMF also potentiates PTP, a form of short-term plasticity, increasing its peak amplitude without impacting its time course. We further investigated the underlying mechanisms and found that calcium channel expression, including the P/Q, N, and R subtypes, at the presynaptic nerve terminal was enhanced, accounting for the increased calcium influx upon stimulation. Thus, we conclude that exposure to ELF-EMF facilitates vesicle endocytosis and synaptic plasticity in a calcium-dependent manner by increasing calcium channel expression at the nerve terminal. PMID- 26887781 TI - Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society. AB - As of December 31, 2013, a total of 7474 liver transplants have been carried out at 66 institutions in Japan. This total included 7255 living-donor transplants and 219 deceased-donor transplants (216 from heart-beating donors and 3 from non heart-beating donors). The annual total of liver transplants in 2013 decreased to 408, from 422 in 2012. The number of liver transplants from living donors decreased to 369, from 381, whereas the number of liver transplants from heart beating deceased donors did not change significantly. The most frequent indication was cholestatic disease, followed by neoplastic disease. In terms of graft liver in living-donor cases, right-lobe graft was the most popular (36%). Patient survival following transplantations from heart-beating donors (1 year, 85.9%; 3 years, 82.6%; 5 years, 81.3%; 10 years, 73.8%) was similar to those from living donors (1 year, 83.8%; 3 years, 79.6%; 5 years, 77.1%; 10 years, 71.9%; 15 years, 67.8%; 20 years, 66.1%). Graft survival was very much the same as patient survival. As for ABO-incompatible transplantation, transplant period affected the outcome significantly, probably due to local infusion therapy and rituximab prophylaxis, which were introduced in many transplant centers after 2000 and 2004, respectively. PMID- 26887782 TI - Antimicrobial resistance genes and modelling of treatment failure in bacterial vaginosis: clinical study of 289 symptomatic women. AB - Clinical management of bacterial vaginosis (BV) is difficult owing to inaccurate diagnostic tests, limited drug choices, and a high rate of recurrence. To our knowledge, there has not been a previous study of antimicrobial resistance (AMR) genes in community practice using next-generation sequencing (NGS). A case control study (1 : 1 age-matched with and without BV) was undertaken in a series of 326 nongravid women of reproductive age with symptoms of BV to determine the prevalence of AMR genes. NGS was used to describe the complete vaginal microbiota and identify bacterial genes associated with resistance to: macrolides and/or lincosamides - ermA, ermB, ermC, erM, ermTR and mefA; tetracyclines, beta lactams, streptomycin, gentamicin and/or tobramycin - acrA, acrB, mecA, tet, tetA, tolC and aac2; 5-nitroimadazoles - nim and nimB; and triazoles - cdr1 and mdr1. An evidence base was created to inform treatment decisions applicable to individual patients. AMR genes were identified in all drug classes: macrolides, 35.2 %; lincosamides, 35.6 %; tetracyclines, 21.8 %; aminoglycosides (streptomycin, gentamicin and tobramycin), 5.2 % each; 5-nitroimidazoles, 0.3 %; and triazoles, 18.7 %. There was more than a fourfold-higher frequency of AMR genes in pathogens from BV than from non-BV patients for macrolides (58.2 versus 12.3 %, respectively), lincosamides (58.9 versus 12.3 %) and tetracyclines (35.6 versus 8.0 %) (Fisher's exact test; all p < 0.001). For each patient with BV, the spectrum of resistance genes was matched to the pathogens present. AMR genes were present in the majority of vaginal microbiomes of patients with symptoms of BV. PMID- 26887783 TI - Vorapaxar and diplopia: Possible off-target PAR-receptor mismodulation. AB - Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, has been evaluated in the successful TRA2P trial and the failed TRACER trial. The drug is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The FDA ruled that the vorapaxar safety profile is acceptable. However, both trials revealed excess diplopia (double vision) usually reversible after vorapaxar. The diplopia risk appears to be small (about 1 extra case per 1,000 treated subjects), but real. Overall, there were 10 placebo and 34 vorapaxar diplopia cases (p=0.018) consistent for TRACER (2 vs 13 cases; p=0.010) and for TRA2P (8 vs 21 cases; p=0.018). Hence, we review the FDA-confirmed evidence and discuss potential causes and implications of such a surprising adverse association, which may be related to off-target PAR receptor mismodulation in the eye. PMID- 26887784 TI - School personnel's self-efficacy in managing food allergy and anaphylaxis. AB - BACKGROUND: Food allergy affects up to 4-7% European schoolchildren. Studies identified important shortcomings on food allergy and anaphylaxis management in schools. In social cognitive theory, personal beliefs in own capabilities influence choices, effort levels, perseverance and performance accomplishments. This study aimed to investigate school personnel's self-efficacy in managing food allergy and anaphylaxis, providing a valid instrument to deeply understand how to support schools to effectively manage students at risk of food reactions. METHODS: A total of 440 schoolteachers and caretakers from north-east Italy completed a questionnaire assessing self-efficacy in managing food allergy and anaphylaxis at school. Exploratory factor analysis was performed. Factors' internal consistency was evaluated using Cronbach's alpha. Factors' scores were estimated using Bartlett approach, and kernel density estimate of distributions was provided. Descriptive statistics explored school personnel's self-efficacy. A regression model assessed the influence of gender, school, job and previous experience. RESULTS: Two factors emerged from exploratory factor analysis related to anaphylaxis management (AM) and food allergy management (FAM). The two subscales both showed good internal consistency. School personnel showed lower self-efficacy in recognizing symptoms, administering drugs and guaranteeing full participation to extra-curricular activities to food-allergic students. Participants who previously had food-allergic students showed a significantly increased self-efficacy in AM and a significantly decreased self-efficacy in FAM. CONCLUSIONS: The study supports the use of self-efficacy scale to identify specific areas where teachers' confidence in their ability to care for food allergic students is especially weak. This would empower the development of training programs specifically tailored to the needs of teachers and caregivers. PMID- 26887785 TI - Analysis of Redox Series of Unsymmetrical 1,4-Diamido-9,10-anthraquinone-Bridged Diruthenium Compounds. AB - The unsymmetrical diruthenium complexes [(bpy)2Ru(II)(MU-H2L(2 ))Ru(III)(acac)2]ClO4 ([3]ClO4), [(pap)2RuII(MU-H2L(2-))Ru(III)(acac)2]ClO4 ([4]ClO4), and [(bpy)2Ru(II)(MU-H2L(2-))Ru(II)(pap)2](ClO4)2 ([5](ClO4)2) have been obtained by way of the mononuclear precursors [(bpy)2Ru(II)(H3L(-))]ClO4 ([1]ClO4) and [(pap)2Ru(II)(H3L(-))]ClO4 ([2]ClO4) (where bpy = 2,2'-bipyridine, pap = 2-phenylazopyridine, acac(-) = 2,4-pentanedionate, and H4L = 1,4-diamino 9,10-anthraquinone). Structural characterization by single-crystal X-ray diffraction and magnetic resonance (nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR)) were used to establish the oxidation state situation in each of the isolated materials. Cyclic voltammetry, EPR, and ultraviolet-visible-near-infrared (UV-vis-NIR) spectroelectrochemistry were used to analyze the multielectron transfer series of the potentially class I mixed valent dinuclear compounds, considering the redox activities of differently coordinated metals, of the noninnocent bridge and of the terminal ligands. Comparison with symmetrical analogues [L2'Ru(MU-H2L)RuL2'](n) (where L' = bpy, pap, or acac(-)) shows that the redox processes in the unsymmetrical dinuclear compounds are not averaged, with respect to the corresponding symmetrical systems, because of intramolecular charge rearrangements involving the metals, the noninnocent bridge, and the ancillary ligands. PMID- 26887786 TI - Laser induced mortality of Anopheles stephensi mosquitoes. AB - Small, flying insects continue to pose great risks to both human health and agricultural production throughout the world, so there remains a compelling need to develop new vector and pest control approaches. Here, we examined the use of short (<25 ms) laser pulses to kill or disable anesthetized female Anopheles stephensi mosquitoes, which were chosen as a representative species. The mortality of mosquitoes exposed to laser pulses of various wavelength, power, pulse duration, and spot size combinations was assessed 24 hours after exposure. For otherwise comparable conditions, green and far-infrared wavelengths were found to be more effective than near- and mid-infrared wavelengths. Pulses with larger laser spot sizes required lower lethal energy densities, or fluence, but more pulse energy than for smaller spot sizes with greater fluence. Pulse duration had to be reduced by several orders of magnitude to significantly lower the lethal pulse energy or fluence required. These results identified the most promising candidates for the lethal laser component in a system being designed to identify, track, and shoot down flying insects in the wild. PMID- 26887788 TI - Early life history of three pelagic-spawning minnows Macrhybopsis spp. in the lower Missouri River. AB - Life-history characteristics of age-0 sturgeon chub Macrhybopsis gelida, shoal chub Macrhybopsis hyostoma and sicklefin chub Macrhybopsis meeki were compared using several methods. All Macrhybopsis species consumed mostly midge pupae, but M. meeki had the most general diet (Levins' index, B = 0.22) compared with M. hyostoma (B = 0.02) and M. gelida (B = 0.09). Morisita's diet overlap index among species pairs ranged from 0.62 to 0.97 and was highest between M. hyostoma and M. gelida. Daily ages estimated from lapilli otoliths for each species ranged from 15 to 43 days for M. gelida, 19 to 44 for M. hyostoma and from 16 to 64 days for M. meeki. Mean growth rates ranged from 0.79 mm day(-1) for M. meeki to 1.39 mm day(-1) for M. gelida. Mortality estimates indicated high daily survivorship rates for M. meeki (0.985), but could not be estimated for the other two species. Hatch date histograms were congruent with the belief that M. hyostoma and M. gelida spawn periodically from June to September. Macrhybopsis meeki, however, appeared to respond to a specific spawning cue as hatch dates were unimodal with a peak in July. These results fill a gap in current knowledge of these imperilled species that can be used to guide management decisions. PMID- 26887787 TI - GeneiASE: Detection of condition-dependent and static allele-specific expression from RNA-seq data without haplotype information. AB - Allele-specific expression (ASE) is the imbalance in transcription between maternal and paternal alleles at a locus and can be probed in single individuals using massively parallel DNA sequencing technology. Assessing ASE within a single sample provides a static picture of the ASE, but the magnitude of ASE for a given transcript may vary between different biological conditions in an individual. Such condition-dependent ASE could indicate a genetic variation with a functional role in the phenotypic difference. We investigated ASE through RNA-sequencing of primary white blood cells from eight human individuals before and after the controlled induction of an inflammatory response, and detected condition dependent and static ASE at 211 and 13021 variants, respectively. We developed a method, GeneiASE, to detect genes exhibiting static or condition-dependent ASE in single individuals. GeneiASE performed consistently over a range of read depths and ASE effect sizes, and did not require phasing of variants to estimate haplotypes. We observed condition-dependent ASE related to the inflammatory response in 19 genes, and static ASE in 1389 genes. Allele-specific expression was confirmed by validation of variants through real-time quantitative RT-PCR, with RNA-seq and RT-PCR ASE effect-size correlations r = 0.67 and r = 0.94 for static and condition-dependent ASE, respectively. PMID- 26887789 TI - Surface Functionalization of Titanium Alloy with miR-29b Nanocapsules To Enhance Bone Regeneration. AB - Titanium and its alloys have been widely used over the past 3 decades as implants for healing bone defects. Nevertheless, the bioinert property of titanium alloy limits its clinical application and surface modification method is frequently performed to improve the biological and chemical properties. Recently, the delivery of microRNA with osteogenesis capability has been recognized as a promising tool to enhance bone regeneration of implants. Here, we developed a biodegradable coating to modify the titanium surface in order to enhance osteogenic bioactivity. The previous developed nanocapsules were used as the building blocks, and then a bioactive titanium coating was designed to entrap the miR-29b nanocapsules. This coating was not only favorable for cell adhesion and growth but also provided sufficient microRNA transfection efficacy and osteoinductive potential, resulting in a significant enhancement of bone regeneration on the surface of bioinert titanium alloy. PMID- 26887790 TI - Thermally robust perpendicular Co/Pd-based synthetic antiferromagnetic coupling enabled by a W capping or buffer layer. AB - Perpendicularly magnetized tunnel junctions (p-MTJs) that contain synthetic antiferromagnetic (SAF) frames show promise as reliable building blocks to meet the demands of perpendicular magnetic anisotropy (PMA)-based spintronic devices. In particular, Co/Pd multilayer-based SAFs have been widely employed due to their outstanding PMA features. However, the widespread utilization of Co/Pd multilayer SAFs coupled with an adjacent CoFeB reference layer (RL) is still a challenge due to the structural discontinuity or intermixing that occurs during high temperature annealing. Thus, we address the thermally robust characteristics of Co/Pd multilayer SAFs by controlling a W layer as a potential buffer or capping layer. The W-capped Co/Pd multilayer SAF, which acts as a pinning layer, exhibited a wide-range plateau with sharp spin-flip and near-zero remanence at the zero field. Structural analysis of the W-capped multilayer SAF exhibited single-crystal-like c-axis oriented crystalline features after annealing at 400 degrees C, thereby demonstrating the applicability of these frames. In addition, when the W layer serving as a buffer layer in the Co/Pd multilayer SAF was coupled with a conventional CoFeB RL, higher annealing stability up to 425 degrees C and prominent antiferromagnetic coupling behavior were obtained. PMID- 26887793 TI - Insight into the Reaction of a Dinuclear Phosphinidene Complex with Nitriles. AB - The phosphinidene complex [Cp*P{W(CO)5}2] (1; Cp*=C5 Me5 ) reacted with malononitrile to give the 1,2-dihydro-1,3,2-diazaphosphinine derivative 2. The reaction of 1 with 1,4-benzodinitrile gave [1,4-{{W(CO)5}2 P-N=C(Cp*)}2 (C6 H4)] (3), the first example of a cumulene-like aminophosphinidene complex. The reaction of 1 with aniline gave the aminophosphinidene complex [(Ph)N(H)P{W(CO)5}2] (4). To compare the reactivity of benzonitrile and aniline with 1, the phosphinidene complex 1 was reacted with three different isomers of aminobenzonitrile (2-, 3-, and 4-aminobenzonitrile). These reactions gave an insight into the reaction pathway of 1 with benzonitrile derivatives. Compounds 5, 6 a, 6 b, and 7, which are derivatives of 1,2-dihydro-1,3,2-diazaphosphinine or benzo-2H-1,2-azaphospholes, were, as well as all other products, characterized by mass spectrometry, NMR and IR spectroscopy, and X-ray structure analysis. PMID- 26887792 TI - Ex vivo expansion of circulating lung tumor cells based on one-step microfluidics based immunomagnetic isolation. AB - We describe a one-step microfludics-based immunomagnetic isolation method to isolate CTCs directly from the whole blood of lung adenocarcinoma patients. This method avoids harsh sample preparation and enrichment steps, and therefore preserves the viability of CTCs during the in vitro isolation. Importantly, isolated, magnetic bead-bearing CTCs are concentrated in a small volume of culture medium with a high CTC density. High cell viability and culturing density promote the ex vivo expansion of limited numbers of CTCs. Expanded CTCs are characterized at the genetic, protein and metabolic levels. PMID- 26887794 TI - Fabrication of Triple-parted Stomata-inspired Membrane with Stimulus-responsive Functions. AB - Hydrogels with controllable morphologies and functional movements present a wide range of practical applications. In this work, a triple-parted stomata-inspired membrane (SIM) was fabricated using a UV light cured hydrogel by polymerization induced diffusion of reactants. A single UV light illumination yielded the SIM that has completely-penetrating pores and semi-penetrated parts. Membranes of various shapes can be easily fabricated within a few minutes by changing the photomask design and composition of the pre-gel solution. Similar to stomatal movement, pores in the fabricated SIM open and close their aperture in response to thermal stimuli. The deformability and transparency of the SIM can be easily controlled for a given application. This SIM exhibits stimulus-response, and therefore has numerous practical applications, such as filter membranes with self adjustable pores, membrane-based sensors, and functional smart membranes. PMID- 26887791 TI - Cell surface localization of importin alpha1/KPNA2 affects cancer cell proliferation by regulating FGF1 signalling. AB - Importin alpha1 is involved in nuclear import as a receptor for proteins with a classical nuclear localization signal (cNLS). Here, we report that importin alpha1 is localized to the cell surface in several cancer cell lines and detected in their cultured medium. We also found that exogenously added importin alpha1 is associated with the cell membrane via interaction with heparan sulfate. Furthermore, we revealed that the cell surface importin alpha1 recognizes cNLS containing substrates. More particularly, importin alpha1 bound directly to FGF1 and FGF2, secreted cNLS-containing growth factors, and addition of exogenous importin alpha1 enhanced the activation of ERK1/2, downstream targets of FGF1 signalling, in FGF1-stimulated cancer cells. Additionally, anti-importin alpha1 antibody treatment suppressed the importin alpha1-FGF1 complex formation and ERK1/2 activation, resulting in decreased cell growth. This study provides novel evidence that functional importin alpha1 is located at the cell surface, where it accelerates the proliferation of cancer cells. PMID- 26887795 TI - Enteral nutrition at home and in nursing homes: an 11-year (2002-2012) epidemiological analysis. AB - BACKGROUND: Home enteral nutrition (HEN) is a well-established extra-hospital therapy that can reduce the risk of malnutrition, ensure the rapid discharge of patients from hospital and significantly reduce health care expenditure. The data reported in this study allow us to understand the relationships between mortality, the place of treatment either at patients' homes (PH) or in nursing homes (NHR) and nutritional status. METHODS: Patients were analyzed according to age, gender, underlying disease, the Karnofsky Index, type of enteral access device (nasogastric tube or percutaneous endoscopic gastrostomy), weight and Body Mass Index (BMI). The duration of HEN therapy was then calculated and the outcome was established on patient mortality or survival. RESULTS: Over an 11-year period, 3246 subjects were administered HEN therapy. The mean duration of HEN therapy was equal to 312+/-487 days at PH and 398+/-573 in NHR. The mean incidence is 406+/-58 patients/million inhabitants/year at PH and 319+/-44 in NHR (mean prevalence rate: 464+/-129 cases/million inhabitants at PH compared to 478+/-164 in NHR). Analysis of variance was used for continuous variables. The study reveals that >8% (8.6% at PH; 8.5% in NHR) of patients die within 10 days of starting HEN therapy. CONCLUSIONS: The study shows a progressive increase in HEN therapy and highlights clinical, organizational and ethical issues, which also need to be analyzed in relation to the progressively aging population. PMID- 26887796 TI - Liver hemodynamic patterns in nonalcoholic steatosis: Doppler ultrasonography and histological evaluation. AB - BACKGROUND: The aim of this study was to evaluate hepatic Doppler ultrasound (US) indices for steatosis diagnosis and grading, having biopsy as reference. METHODS: Doppler and conventional US were performed in 49 healthy volunteers, without risk factors for nonalcoholic fatty liver disease (NAFLD), and in 49 patients with NAFLD and at least one risk factor: obesity, dyslipidemia and/or diabetes mellitus. Significant alcohol intake and hepatitis B or C were exclusion criteria. NAFLD patients were biopsied, and steatosis severity graded histologically. Portal Venous Pulsatility Index (PVI), Hepatic Artery Resistance Index (HARI) and Pulsatility Index (HAPI) were analyzed in hilum. Hepatic vein waveform pattern (HVWP) was classified as triphasic, biphasic or monophasic. Two pathologists analyzed histological samples. ROC curve defined sensitivity and specificity and multivariate analysis defined an equation for classifying patients. RESULTS: In NAFLD group, 89.79% had histologic criteria for non alcoholic steatohepatitis (NASH). Mild steatosis was present in 44.89%, moderate steatosis in 38.77% and severe steatosis in 16.32%. In NAFLD group, 65.29% were obese and body mass index (BMI) had significant correlation with steatosis grading (r=0.77; P<0.0001). PVI correlated with presence of steatosis (r=-0.69, P<0.0001) as HVWP (r=-0.61, P< 0.0001). PVI ideal cutoff for predicting steatosis was 0.26 (sensitivity, 91%; specificity, 79.6%). The equation 16.15PVI+1.96HVWP enables to differentiate the healthy and the steatosis patients. HARI and HAPI could not differentiate the healthy from the steatosis group. None of the indices correlated with steatosis grading. CONCLUSIONS: Portal and hepatic vein indices allow non-invasive steatosis diagnosis but are limited to quantify it. Histology remains important for steatohepatitis diagnosis and for steatosis grading. PMID- 26887797 TI - Cancer and life-history traits: lessons from host-parasite interactions. AB - Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations. PMID- 26887798 TI - Sex-dependent association between erythrocyte n-3 PUFA and type 2 diabetes in older overweight people. AB - The association between n-3 PUFA intake and type 2 diabetes (T2D) is unclear, and studies relating objective biomarkers of n-3 PUFA consumption to diabetic status remain limited. The aim of this study was to determine whether erythrocyte n-3 PUFA levels (n-3 index; n-3I) are associated with T2D in a cohort of older adults (n 608). To achieve this, the n-3I (erythrocyte %EPA+%DHA) was determined by GC and associated with fasting blood glucose; HbA1c; and plasma insulin. Insulin resistance (IR) was assessed using the homeostatic model assessment of insulin resistance (HOMA--IR). OR for T2D were calculated for each quartile of n-3I. In all, eighty-two type 2 diabetic (46.3 % female; 76.7 (sd 5.9) years) and 466 non diabetic (57.9 % female; 77.8 (sd 7.1) years) individuals were included in the analysis. In overweight/obese (BMI>=27 kg/m2), the prevalence of T2D decreased across ascending n-3I quartiles: 1.0 (reference), 0.82 (95 % CI 0.31, 2.18), 0.56 (95 % CI 0.21, 1.52) and 0.22 (95 % CI 0.06, 0.82) (P trend=0.015). A similar but non-significant trend was seen in overweight men. After adjusting for BMI, no associations were found between n-3I and fasting blood glucose, HbA1c, insulin or HOMA-IR. In conclusion, higher erythrocyte n-3 PUFA status may be protective against the development of T2D in overweight women. Further research is warranted to determine whether dietary interventions that improve n-3 PUFA status can improve measures of IR, and to further elucidate sex-dependent differences. PMID- 26887799 TI - Some coumarins and benzoxazinones as potent paraoxonase 1 inhibitors. AB - In this study, we aimed to investigate the effect of some coumarin and benzoxazinone derivatives on the activity of human PON1. Human serum paraoxonase 1 was purified from fresh human serum blood by two-step procedures that are ammonium sulfate precipitation (60-80%) and then hydrophobic interaction chromatography (Sepharose 4B, L-tyrosine and 1-napthylamine). The enzyme was purified 232-fold with a final specific activity of 27.1 U/mg. In vitro effects of some previously synthesized ionic coumarin or benzoxazinone derivatives (1-21) on purified PON1 activity were investigated. Compound 14 (1-(2,3,4,5,6) pentamethylbenzyl-3-(6,8-dimethyl-2H-chromen-2-one-4-yl))benzimidazolium chloride was found out as the strongest inhibitor (IC50 = 7.84 MUM) for PON1 among the compounds. Kinetic investigation and molecular docking study were evaluated for one of the most active compounds (compound 12) and obtained data showed that this compound is competitive inhibitor of PON1 and interact with Leu262 and Ser263 in the active site of PON1. Moreover, coumarin derivatives were found out as the more potent inhibitors for PON1 than benzoxazinone derivatives. PMID- 26887800 TI - Prescription patterns of antiepileptic drugs in young women: development of a tool to distinguish between epilepsy and psychiatric disorders. AB - BACKGROUND: Antiepileptic drugs (AEDs) are also prescribed for therapeutic indications other than epilepsy (EPI), namely, psychiatric disorders (PSY). Our aim was to develop an algorithm able to distinguish between EPI and PSY among childbearing age women based on differences in AED exposure in these patient groups. METHODS: Two groups of women (18-45 years) with EPI or PSY treated with AEDs in the first semester of 2010 or 2011 were extracted from paper or electronic medical charts of specialized centers. Through the prescription database of Bologna Local Health Authority (Italy), AEDs, treatment schedule and co-treatments were collected for each patient. A prescription-based hierarchical classification system was developed. The algorithm obtained was subsequently validated on internal and external data. RESULTS: Eighty-one EPI and 94 PSY subjects were recruited. AED monotherapy was the most common choice in both groups (69% EPI vs 79% PSY). Some AEDs were used only in EPI, others exclusively in PSY. Co-treatments with antipsychotics (6% vs 67%), lithium (0% vs 9%), and antidepressants (7% vs 70%) were fewer in EPI than in PSY. The hierarchical classification system identified antipsychotics, SSRIs (Selective Serotonin Reuptake Inhibitors), and number of AEDs as variables to discriminate EPI and PSY, with an overall error rate estimate of 9.7% (95%CI: 5.3% to 14.1%). CONCLUSION: Among the differences between EPI and PSY, prescription data alone allowed an algorithm to be developed to diagnose each childbearing age woman receiving AEDs. This approach will be useful to stratify patients for risk estimates of AED-treated patients based on administrative databases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887803 TI - Color Correlations among Six Types of Permanent Anterior Teeth. AB - STATEMENT OF PROBLEM: When multiple teeth are missing, the color for missing teeth should be estimated based on the color of remaining teeth. PURPOSE: The purpose was to determine the strength of color correlations among six types of permanent anterior teeth. METHODS: Color of 12 anterior teeth was measured by Shade Vision System for 47 volunteers. The color coordinates in each type of teeth such as maxillary central incisor (MX1), lateral incisor (MX2), and canine (MX3), and mandibular central incisor (MD1), lateral incisor (MD2), and canine (MD3) were determined. Correlations and differences among the corresponding color coordinates of each type of teeth were determined. RESULTS: Compared with MX1, the differences were in the range of -3.2 to -6.5 in L*, 0.5 to 2.7 in a*, -0.7 to 7.5 in b*, and the color difference (DeltaE*ab ) was 4.5 to 10.3. The color difference by DeltaE00 formula was 3.1-6.7. Although the color coordinates were different by tooth type, they generally showed correlations (p < 0.001). CONCLUSIONS: For the color estimation of missing MX1, the color coordinates of MD1 were the strongest predictors. In case of missing MX3, L* and a* of MD3 and b* of MX1 were the strongest predictors for each corresponding coordinates. CLINICAL SIGNIFICANCE: The color for missing teeth, especially for maxillary central incisor and maxillary and mandibular canines, could be estimated based on those of the same type teeth on the opposing arch. These results should be applied for clinical color selection for missing teeth.(J Esthet Restor Dent 28:S5-S13, 2016). PMID- 26887802 TI - Proteomic analysis for the impact of hypercholesterolemia on expressions of hepatic drug transporters and metabolizing enzymes. AB - 1. Our objective is to investigate the alterations of hepatic drug transporters and metabolizing enzymes in hypercholesterolemia. Male Sprague-Dawley rats were fed high-cholesterol chows for 8 weeks to induce hypercholesterolemia. Protein levels of hepatic drug transporters and metabolizing enzymes were analyzed by iTRAQ labeling coupled with LC TRIPLE-TOF. 2. Total 239 differentially expressed proteins were identified using proteomic analysis. Among those, protein levels of hepatic drug transporters (MRP2, ABCD3, OAT2, SLC25A12, SCL38A3, SLC2A2 and SLC25A5) and metabolizing enzymes (CYP2B3, CYP2C7, CYP2C11, CYP2C13, CYP4A2 and UGT2B) were markedly reduced, but the levels of CYP2C6 and CYP2E1 were increased in hypercholesterolemia group compared to control. Decreased expressions of drug transporters MRP2 and OAT2 were further confirmed by real time quantitative PCR (RT-qPCR) and western blot. 3. Ingenuity pathway analysis revealed that these differentially expressed proteins were regulated by various signaling pathways including nuclear receptors and inflammatory cytokines. One of the nuclear receptor candidates, liver X receptor alpha (LXRalpha), was further validated by RT-qPCR and western blot. Additionally, LXRalpha agonist T0901317 rescued the reduced expressions of MRP2 and OAT2 in HepG2 cells in hypercholesterolemic serum treatment. 4. Our present results indicated that hypercholesterolemia affected the expressions of various drug transporters and metabolizing enzymes in liver via nuclear receptors pathway. Especially, decreased function of LXRalpha contributes to the reduced expressions of MRP2 and OAT2. PMID- 26887801 TI - Evaluation of lesser metatarsophalangeal joint plantar plate tears with contrast enhanced and fat-suppressed MRI. AB - OBJECTIVE: To present findings of plantar plate (PP) lesions from MRI with administration of gadolinium and to differentiate PP lesions from others causes of metatarsalgia. MATERIALS AND METHODS: Two musculoskeletal radiologists reviewed 249 contrast-enhanced forefoot MRI scans from patients with metatarsalgia between June 2012 and June 2013. Evaluations focused on hyper vascularized/fibrous tissue and other findings associated with PP tears. RESULTS: Fifty-nine patients had PP tears, 59 % were female. Most of these patients, 48/59 (81.4 %), had a single metatarsophalangeal (MTP) PP lesion in one foot, although 7/59 patients had one lesion in each foot, 3/59 (5.1 %) had two in one foot, and 1/59 (1.7 %) had three lesions in one foot. The second MTP joint was the most common location for PP tears (n = 56), followed by the third (n = 12) and fourth (n = 3) MTP joints. Lateral (n = 33) and full thickness (n = 28) PP lesions were the most frequent, and central (n = 3) and lateral/central (n = 7) tears were less prevalent. Fifty (70.5 %) PP lesions showed pericapsular fibrosis in pre contrast sequences, and 21 (29.5 %) were visible only after administration of gadolinium. All PP lesions had collateral ligament involvement. Others findings included interosseous tendon lesions (n = 29), interosseous tendon rupture (n = 29), synovitis (n = 49), flexor tenosynovitis (n = 28), crossover toe (n = 2), hammertoe (n = 1), intermetatarsal space (IS) neuromas (n = 11), and third IS neuromas (n = 12). CONCLUSION: PP tears are a common cause of metatarsalgia, accounting for more than 20 % of cases in our sample. A substantial portion of the lesions (29.5 %) became visible only after the administration of gadolinium. PMID- 26887804 TI - The N-terminal sequence of the extrinsic PsbP protein modulates the redox potential of Cyt b559 in photosystem II. AB - The PsbP protein, an extrinsic subunit of photosystem II (PSII) in green plants, is known to induce a conformational change around the catalytic Mn4CaO5 cluster securing the binding of Ca(2+) and Cl(-) in PSII. PsbP has multiple interactions with the membrane subunits of PSII, but how these affect the structure and function of PSII requires clarification. Here, we focus on the interactions between the N-terminal residues of PsbP and the alpha subunit of Cytochrome (Cyt) b559 (PsbE). A key observation was that a peptide fragment formed of the first N terminal 15 residues of PsbP, 'pN15', was able to convert Cyt b559 into its HP form. Interestingly, addition of pN15 to NaCl-washed PSII membranes decreased PSII's oxygen-evolving activity, even in the presence of saturating Ca(2+) and Cl(-) ions. In fact, pN15 reversibly inhibited the S1 to S2 transition of the OEC in PSII. These data suggest that pN15 can modulate the redox property of Cyt b559 involved in the side-electron pathway in PSII. This potential change of Cyt b559, in the absence of the C-terminal domain of PsbP, however, would interfere with any electron donation from the Mn4CaO5 cluster, leading to the possibility that multiple interactions of PsbP, binding to PSII, have distinct roles in regulating electron transfer within PSII. PMID- 26887805 TI - Serum nuclear magnetic resonance-based metabolomics and outcome in diffuse large B-cell lymphoma patients - a pilot study. AB - The prognosis for diffuse large B-cell lymphoma (DLBCL) patients with early relapse or refractory disease is dismal. To determine if clinical outcome correlated to diverse serum metabolomic profiles, we used (1)H nuclear magnetic resonance (NMR) spectroscopy and compared two groups of DLBCL patients treated with immunochemotherapy: i) refractory/early relapse (REF/REL; n=27) and ii) long term progression-free (CURED; n = 60). A supervised multivariate analysis showed a separation between the groups. Among discriminating metabolites higher in the REF/REL group were the amino acids lysine and arginine, the degradation product cadaverine and a compound in oxidative stress (2-hydroxybutyrate). In contrast, the amino acids aspartate, valine and ornithine, and a metabolite in the glutathione cycle, pyroglutamate, were higher in CURED patients. Together, our data indicate that NMR-based serum metabolomics can identify a signature for DLBCL patients with high-risk of failing immunochemotherapy, prompting for larger validating studies which could lead to more individualized treatment of this disease. PMID- 26887806 TI - Diabetes Caused by Elastase-Cre-Mediated Pdx1 Inactivation in Mice. AB - Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors, and ultimately fewer beta cells. Notably, postnatal expansion of the endocrine cell content was extremely poor, and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages. PMID- 26887807 TI - Paraneoplastic lipase and amylase production in a patient with small-cell lung cancer: case report. AB - BACKGROUND: Small-cell lung cancer (SCLC) is known to express antigens of both the neural crest and epithelium, and to secrete polypeptide hormones and enzymes. Anecdotal reports correlate lung cancer with marked hyperamylasemia, and a review of the literature reveals only one case of metastatic SCLC linked to high paraneoplastic lipase production. CASE PRESENTATION: We present the case of a patient with metastatic SCLC who showed both lipase and pancreatic isoamylase elevation in the absence of acute pancreatitis. Chemotherapy resulted in a rapid reduction in serum lipase and in pancreatic isoamylase which was correlated with the radiological response of the tumor to therapy. Lipase and pancreatic isoamylase expression in tumor cells from the lung biopsy was confirmed by immunohistochemical staining. CONCLUSIONS: This is a very rare case of paraneoplastic syndrome linked to metastatic SCLC. The enzymes secreted could be used as markers of response to treatment until clonal selection mechanisms and intratumor heterogeneity induce changes in biochemical characteristics and consequently in tumor behavior. PMID- 26887808 TI - Ambulatory Assessment. AB - In recent years, significant technological advances have changed our understanding of dynamic processes in clinical psychology. A particularly important agent of change has been ambulatory assessment (AA). AA is the assessment of individuals in their daily lives, combining the twin benefits of increased ecological validity and minimized retrospective biases. These benefits make AA particularly well-suited to the assessment of dynamic processes, and recent advancements in technology are providing exciting new opportunities to understand these processes in new ways. In the current article, we briefly detail the capabilities currently offered by smartphones and mobile physiological devices, as well as some of the practical and ethical challenges of incorporating these new technologies into AA research. We then provide several examples of recent innovative applications of AA methodology in clinical research, assessment, and intervention and provide a case example of AA data generated from a study utilizing multiple mobile devices. In this way, we aim to provide a sense of direction for researchers planning AA studies of their own. PMID- 26887809 TI - Spanish Validation of the Avoidance and Fusion Questionnaire for Youth (AFQ-Y). AB - Psychological inflexibility (PI) refers to the overarching and nonadaptive avoidance of thoughts and feelings. PI is a transdiagnostic process that is present in numerous psychopathologies, such as anxiety and mood disorders, addictive behaviors, and chronic pain, as presented by American adults and adolescents. Despite the high rates of depression and depressed mood among Spanish and Latino adolescents and the observed relation between PI and adjustment problems at this age, an instrument assessing PI in Spanish-speaking adolescents is lacking. In this study, we assessed the psychometric properties of a Spanish adaptation of the Avoidance and Fusion Questionnaire for Youth with 483 students from Spain (mean age 13.89 years). The Spanish Avoidance and Fusion Questionnaire for Youth proved to be a two-factor psychometrically sound instrument. Total PI scores correlated positively with depression and negatively with satisfaction with life. The predictive validity results showed cognitive fusion and experiential avoidance to be two interrelated but distinct processes that characterize PI. PMID- 26887810 TI - The CES-D as a Measure of Psychological Distress Among International Students: Measurement and Structural Invariance Across Gender. AB - Detecting psychological distress among international students can be challenging given diverse languages, cultural backgrounds, and lack of refined measurement properties of measures tailored to international students. Despite the challenges, ensuring that a psychological distress measure works effectively has considerable potential value for assessment purposes. The current study evaluates the measurement properties of a short 10-item version of Radloff's Center for Epidemiologic Studies Depression Scale (CES-D). Grounded in long-standing evidence on gender differences in depressive symptoms, specific attention was given to examining measurement invariance of the CES-D Short-form across women and men. Based on a large, two-cohort sample of international students ( N = 468), and through multiple analyses evaluating factor structure and measurement invariance, we derived an even briefer, seven-item single-factor form of the CES D (CES-D Short-form International) that can be used with international students. PMID- 26887811 TI - Convergent and Predictive Validity of the Jesness Inventory in a Sample of Juvenile Offenders. AB - The present study examined the convergent and predictive validity of the Jesness Inventories (JI) in a sample of 138 juvenile offenders, completed in the course of routine service delivery. JI profiles were compared with ratings on three standardized forensic clinical scales: the Youth Level of Service/Case Management Inventory, Psychopathy Checklist: Youth Version, and Violence Risk Scale-Youth Version. The JI Asocial Index and the Undersocialized Active and Group-Oriented Conformist Interpersonal Maturity Level (I-level) subtypes demonstrated the strongest pattern of convergence and most consistently predicted recidivism. The Asocial Index did not incrementally predict recidivism after controlling for scores on the standardized forensic clinical scales; however, meaningful differences among broad I-Level groups (I-3 and I-4) remained after controlling for risk. Risk-need-responsivity applications of the JI (i.e., in terms of treatment dosage, identifying treatment targets, and adaptation of services) are discussed within the context of a comprehensive forensic assessment framework to inform case formulation, service delivery, and decision making with justice involved youth. PMID- 26887812 TI - Joint 2D and 3D phase processing for quantitative susceptibility mapping: application to 2D echo-planar imaging. AB - Quantitative susceptibility mapping (QSM) measures tissue magnetic susceptibility and typically relies on time-consuming three-dimensional (3D) gradient-echo (GRE) MRI. Recent studies have shown that two-dimensional (2D) multi-slice gradient echo echo-planar imaging (GRE-EPI), which is commonly used in functional MRI (fMRI) and other dynamic imaging techniques, can also be used to produce data suitable for QSM with much shorter scan times. However, the production of high quality QSM maps is difficult because data obtained by 2D multi-slice scans often have phase inconsistencies across adjacent slices and strong susceptibility field gradients near air-tissue interfaces. To address these challenges in 2D EPI-based QSM studies, we present a new data processing procedure that integrates 2D and 3D phase processing. First, 2D Laplacian-based phase unwrapping and 2D background phase removal are performed to reduce phase inconsistencies between slices and remove in-plane harmonic components of the background phase. This is followed by 3D background phase removal for the through-plane harmonic components. The proposed phase processing was evaluated with 2D EPI data obtained from healthy volunteers, and compared against conventional 3D phase processing using the same 2D EPI datasets. Our QSM results were also compared with QSM values from time consuming 3D GRE data, which were taken as ground truth. The experimental results show that this new 2D EPI-based QSM technique can produce quantitative susceptibility measures that are comparable with those of 3D GRE-based QSM across different brain regions (e.g. subcortical iron-rich gray matter, cortical gray and white matter). This new 2D EPI QSM reconstruction method is implemented within STI Suite, which is a comprehensive shareware for susceptibility imaging and quantification. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887813 TI - Classification of low quality cells from single-cell RNA-seq data. AB - Single-cell RNA sequencing (scRNA-seq) has broad applications across biomedical research. One of the key challenges is to ensure that only single, live cells are included in downstream analysis, as the inclusion of compromised cells inevitably affects data interpretation. Here, we present a generic approach for processing scRNA-seq data and detecting low quality cells, using a curated set of over 20 biological and technical features. Our approach improves classification accuracy by over 30 % compared to traditional methods when tested on over 5,000 cells, including CD4+ T cells, bone marrow dendritic cells, and mouse embryonic stem cells. PMID- 26887814 TI - Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development. AB - BACKGROUND: Wood development is of outstanding interest both to basic research and industry due to the associated cellulose and lignin biomass production. Efforts to elucidate wood formation (which is essential for numerous aspects of both pure and applied plant science) have been made using transcriptomic analyses and/or low-resolution sampling. However, transcriptomic data do not correlate perfectly with levels of expressed proteins due to effects of post-translational modifications and variations in turnover rates. In addition, high-resolution analysis is needed to characterize key transitions. In order to identify protein profiles across the developmental region of wood formation, an in-depth and tissue specific sampling was performed. RESULTS: We examined protein profiles, using an ultra-performance liquid chromatography/quadrupole time of flight mass spectrometry system, in high-resolution tangential sections spanning all wood development zones in Populus tremula from undifferentiated cambium to mature phloem and xylem, including cell expansion and cell death zones. In total, we analyzed 482 sections, 20-160 MUm thick, from four 47-year-old trees growing wild in Sweden. We obtained high quality expression profiles for 3,082 proteins exhibiting consistency across the replicates, considering that the trees were growing in an uncontrolled environment. A combination of Principal Component Analysis (PCA), Orthogonal Projections to Latent Structures (OPLS) modeling and an enhanced stepwise linear modeling approach identified several major transitions in global protein expression profiles, pinpointing (for example) locations of the cambial division leading to phloem and xylem cells, and secondary cell wall formation zones. We also identified key proteins and associated pathways underlying these developmental landmarks. For example, many of the lignocellulosic related proteins were upregulated in the expansion to the early developmental xylem zone, and for laccases with a rapid decrease in early xylem zones. We observed upregulation of two forms of xylem cysteine protease (Potri.002G005700.1 and Potri.005G256000.2; Pt-XCP2.1) in early xylem and their downregulation in late maturing xylem. Our data also show that Pt-KOR1.3 (Potri.003G151700.2) exhibits an expression pattern that supports the hypothesis put forward in previous studies that this is a key xyloglucanase involved in cellulose biosynthesis in primary cell walls and reduction of cellulose crystallinity in secondary walls. CONCLUSION: Our novel multivariate approach highlights important processes and provides confirmatory insights into the molecular foundations of wood development. PMID- 26887815 TI - STAT4-associated natural killer cell tolerance following liver transplantation. AB - OBJECTIVE: Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. DESIGN: Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. RESULTS: NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-gamma secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNgamma expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV. CONCLUSIONS: LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease. PMID- 26887816 TI - The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls. AB - OBJECTIVE: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease. DESIGN: We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, QFDR<0.20) in both panels were reported, followed by a combined comparison of all samples against UC. RESULTS: Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78. CONCLUSIONS: Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC. PMID- 26887817 TI - Solving a disaster following coronary bypass operation. PMID- 26887818 TI - alpha-Conotoxin Vc1.1 inhibits human dorsal root ganglion neuroexcitability and mouse colonic nociception via GABAB receptors. AB - OBJECTIVE: alpha-Conotoxin Vc1.1 is a small disulfide-bonded peptide from the venom of the marine cone snail Conus victoriae. Vc1.1 has antinociceptive actions in animal models of neuropathic pain, but its applicability to inhibiting human dorsal root ganglion (DRG) neuroexcitability and reducing chronic visceral pain (CVP) is unknown. DESIGN: We determined the inhibitory actions of Vc1.1 on human DRG neurons and on mouse colonic sensory afferents in healthy and chronic visceral hypersensitivity (CVH) states. In mice, visceral nociception was assessed by neuronal activation within the spinal cord in response to noxious colorectal distension (CRD). Quantitative-reverse-transcription-PCR, single-cell reverse-transcription-PCR and immunohistochemistry determined gamma-aminobutyric acid receptor B (GABABR) and voltage-gated calcium channel (CaV2.2, CaV2.3) expression in human and mouse DRG neurons. RESULTS: Vc1.1 reduced the excitability of human DRG neurons, whereas a synthetic Vc1.1 analogue that is inactive at GABABR did not. Human DRG neurons expressed GABABR and its downstream effector channels CaV2.2 and CaV2.3. Mouse colonic DRG neurons exhibited high GABABR, CaV2.2 and CaV2.3 expression, with upregulation of the CaV2.2 exon-37a variant during CVH. Vc1.1 inhibited mouse colonic afferents ex vivo and nociceptive signalling of noxious CRD into the spinal cord in vivo, with greatest efficacy observed during CVH. A selective GABABR antagonist prevented Vc1.1 induced inhibition, whereas blocking both CaV2.2 and CaV2.3 caused inhibition comparable with Vc1.1 alone. CONCLUSIONS: Vc1.1-mediated activation of GABABR is a novel mechanism for reducing the excitability of human DRG neurons. Vc1.1 induced activation of GABABR on the peripheral endings of colonic afferents reduces nociceptive signalling. The enhanced antinociceptive actions of Vc1.1 during CVH suggest it is a novel candidate for the treatment for CVP. PMID- 26887819 TI - LncDisease: a sequence based bioinformatics tool for predicting lncRNA-disease associations. AB - LncRNAs represent a large class of noncoding RNA molecules that have important functions and play key roles in a variety of human diseases. There is an urgent need to develop bioinformatics tools as to gain insight into lncRNAs. This study developed a sequence-based bioinformatics method, LncDisease, to predict the lncRNA-disease associations based on the crosstalk between lncRNAs and miRNAs. Using LncDisease, we predicted the lncRNAs associated with breast cancer and hypertension. The breast-cancer-associated lncRNAs were studied in two breast tumor cell lines, MCF-7 and MDA-MB-231. The qRT-PCR results showed that 11 (91.7%) of the 12 predicted lncRNAs could be validated in both breast cancer cell lines. The hypertension-associated lncRNAs were further evaluated in human vascular smooth muscle cells (VSMCs) stimulated with angiotensin II (Ang II). The qRT-PCR results showed that 3 (75.0%) of the 4 predicted lncRNAs could be validated in Ang II-treated human VSMCs. In addition, we predicted 6 diseases associated with the lncRNA GAS5 and validated 4 (66.7%) of them by literature mining. These results greatly support the specificity and efficacy of LncDisease in the study of lncRNAs in human diseases. The LncDisease software is freely available on the Software Page: http://www.cuilab.cn/. PMID- 26887823 TI - A latent process model for forecasting multiple time series in environmental public health surveillance. AB - This paper outlines a latent process model for forecasting multiple health outcomes arising from a common environmental exposure. Traditionally, surveillance models in environmental health do not link health outcome measures, such as morbidity or mortality counts, to measures of exposure, such as air pollution. Moreover, different measures of health outcomes are treated as independent, while it is known that they are correlated with one another over time as they arise in part from a common underlying exposure. We propose modelling an environmental exposure as a latent process, and we describe the implementation of such a model within a hierarchical Bayesian framework and its efficient computation using integrated nested Laplace approximations. Through a simulation study, we compare distinct univariate models for each health outcome with a bivariate approach. The bivariate model outperforms the univariate models in bias and coverage of parameter estimation, in forecast accuracy and in computational efficiency. The methods are illustrated with a case study using healthcare utilization and air pollution data from British Columbia, Canada, 2003 2011, where seasonal wildfires produce high levels of air pollution, significantly impacting population health. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887820 TI - Homologous DNA strand exchange activity of the human mitochondrial DNA helicase TWINKLE. AB - A crucial component of the human mitochondrial DNA replisome is the ring-shaped helicase TWINKLE-a phage T7-gene 4-like protein expressed in the nucleus and localized in the human mitochondria. Our previous studies showed that despite being a helicase, TWINKLE has unique DNA annealing activity. At the time, the implications of DNA annealing by TWINKLE were unclear. Herein, we report that TWINKLE uses DNA annealing function to actively catalyze strand-exchange reaction between the unwinding substrate and a homologous single-stranded DNA. Using various biochemical experiments, we demonstrate that the mechanism of strand exchange involves active coupling of unwinding and annealing reactions by the TWINKLE. Unlike strand-annealing, the strand-exchange reaction requires nucleotide hydrolysis and greatly stimulated by short region of homology between the recombining DNA strands that promote joint molecule formation to initiate strand-exchange. Furthermore, we show that TWINKLE catalyzes branch migration by resolving homologous four-way junction DNA. These four DNA modifying activities of TWINKLE: strand-separation, strand-annealing, strand-exchange and branch migration suggest a dual role of TWINKLE in mitochondrial DNA maintenance. In addition to playing a major role in fork progression during leading strand DNA synthesis, we propose that TWINKLE is involved in recombinational repair of the human mitochondrial DNA. PMID- 26887824 TI - Melatonin mediates the stabilization of DELLA proteins to repress the floral transition in Arabidopsis. AB - Precise floral transition from vegetative growth phase to reproductive growth phase is very important in plant life cycle. In flowering genetic pathways, DELLA proteins are master transcriptional regulators of gibberelic acid (GA) pathway, and FLOWERING LOCUS C (FLC) is a core repressor of vernalization pathway as well as downstream of DELLAs. As a crucial messenger in plants, the possible involvement of melatonin (N-acetyl-5-methoxytryptamine) in flowering and underlying molecular mechanism are unknown in Arabidopsis. In this study, we found that exogenous melatonin treatment delayed floral transition in Arabidopsis. Exogenous melatonin treatment conferred protein stabilizations of DELLAs [REPRESSOR of ga1-3 (RGA) and RGA-LIKE3 (RGL3)], without regulating the transcripts of DELLAs and endogenous GA level. Notably, exogenous melatonin delayed plant flowering and DELLA-activated transcripts of FLC were alleviated in della mutants, and those were exacerbated in DELLA overexpressing plants. Taken together, this study provides direct link between melatonin and floral transition, and indicates the novel involvement of DELLAs-activated FLC in melatonin-mediated flowering in Arabidopsis. PMID- 26887826 TI - Knowledge of vitreomacular traction (VMT) scenarios: Is doing nothing still a beneficial alternative and, if so, when? PMID- 26887825 TI - Pulse waveform analysis in the optic nerve head circulation reflects systemic vascular resistance obtained via a Swan-Ganz catheter. AB - PURPOSE: To determine whether a pulse waveform analysis in the optic nerve head (ONH) circulation as determined by laser speckle flowgraphy (LSFG) can provide systemic hemodynamic values - the systemic vascular resistance (SVR) in particular - similar to those obtained by using a Swan-Ganz catheter, which is an invasive method. METHOD: Sixteen consecutive subjects were examined. Hemodynamic monitoring was obtained from right heart catheterization with a Swan-Ganz catheter and coronary angiography without an intracoronary nitroglycerin administration. Direct blood pressure was measured with a trans-radial approach. Single regression analyses were used to determine the relationship between the blowout score and blowout time, which are the items of the pulse waveform analysis in the ONH, by using LSFG and the hemodynamic parameters. RESULTS: The blowout time was significantly and negatively correlated with the SVR (r = -0.52, p = 0.04), the ocular perfusion pressure with the mean arterial blood pressure of the radial artery (r = -0.52, p = 0.04) and the radial artery pulse pressure (r = -0.52, p = 0.04).The pulmonary capillary wedge pressure (r = -0.44, p = 0.09) and the mean arterial blood pressure of the radial artery (r = -0.44, p = 0.09) tended to be correlated with the blowout time, but did not reach significance. The blowout score was significantly and negatively correlated with the radial artery blood pressure (r = -0.51, p = 0.046). CONCLUSION: A pulse waveform analysis in the ONH by LSFG may be one of the useful methods for understanding the SVR. PMID- 26887821 TI - At the interface of antioxidant signalling and cellular function: Key polyphenol effects. AB - The hypothesis that dietary (poly)phenols promote well-being by improving chronic disease-risk biomarkers, such as endothelial dysfunction, chronic inflammation and plasma uric acid, is the subject of intense current research, involving human interventions studies, animal models and in vitro mechanistic work. The original claim that benefits were due to the direct antioxidant properties of (poly)phenols has been mostly superseded by detailed mechanistic studies on specific molecular targets. Nevertheless, many proposed mechanisms in vivo and in vitro are due to modulation of oxidative processes, often involving binding to specific proteins and effects on cell signalling. We review the molecular mechanisms for 3 actions of (poly)phenols on oxidative processes where there is evidence in vivo from human intervention or animal studies. (1) Effects of (poly) phenols on pathways of chronic inflammation leading to prevention of some of the damaging effects associated with the metabolic syndrome. (2) Interaction of (poly)phenols with endothelial cells and smooth muscle cells, leading to effects on blood pressure and endothelial dysfunction, and consequent reduction in cardiovascular disease risk. (3) The inhibition of xanthine oxidoreductase leading to modulation of intracellular superoxide and plasma uric acid, a risk factor for developing type 2 diabetes. PMID- 26887827 TI - Prospects to regain the ability to accommodate. PMID- 26887828 TI - Re: "Incidence of post-cataract endophthalmitis with intracameral cefuroxime" letter to the editor. PMID- 26887829 TI - Melanocortin 1 receptor agonist protects podocytes through catalase and RhoA activation. AB - Drugs containing adrenocorticotropic hormone have been used as therapy for patients with nephrotic syndrome. We have previously shown that adrenocorticotropic hormone and a selective agonist for the melanocortin 1 receptor (MC1R) exert beneficial actions in experimental membranous nephropathy with reduced proteinuria, reduced oxidative stress, and improved glomerular morphology and function. Our hypothesis is that MC1R activation in podocytes elicits beneficial effects by promoting stress fibers and maintaining podocyte viability. To test the hypothesis, we cultured podocytes and used highly specific agonists for MC1R. Podocytes were subjected to the nephrotic-inducing agent puromycin aminonucleoside, and downstream effects of MC1R activation on podocyte survival, antioxidant defense, and cytoskeleton dynamics were studied. To increase the response and enhance intracellular signals, podocytes were transduced to overexpress MC1R. We showed that puromycin promotes MC1R expression in podocytes and that activation of MC1R promotes an increase of catalase activity and reduces oxidative stress, which results in the dephosphorylation of p190RhoGAP and formation of stress fibers through RhoA. In addition, MC1R agonists protect against apoptosis. Together, these mechanisms protect the podocyte against puromycin. Our findings strongly support the hypothesis that selective MC1R-activating agonists protect podocytes and may therefore be useful to treat patients with nephrotic syndromes commonly considered as podocytopathies. PMID- 26887830 TI - Loss of diacylglycerol kinase epsilon in mice causes endothelial distress and impairs glomerular Cox-2 and PGE2 production. AB - Thrombotic microangiopathy (TMA) is a disorder characterized by microvascular occlusion that can lead to thrombocytopenia, hemolytic anemia, and glomerular damage. Complement activation is the central event in most cases of TMA. Primary forms of TMA are caused by mutations in genes encoding components of the complement or regulators of the complement cascade. Recently, we and others have described a genetic form of TMA caused by mutations in the gene diacylglycerol kinase-epsilon (DGKE) that encodes the lipid kinase DGKepsilon (Lemaire M, Fremeaux-Bacchi V, Schaefer F, Choi MR, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji WZ, Overton JD, Mane SM, Nurnberg G, Altmuller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nurnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP. Nat Genet 45: 531-536, 2013; Ozaltin F, Li BH, Rauhauser A, An SW, Soylemezoglu O, Gonul II, Taskiran EZ, Ibsirlioglu T, Korkmaz E, Bilginer Y, Duzova A, Ozen S, Topaloglu R, Besbas N, Ashraf S, Du Y, Liang CY, Chen P, Lu DM, Vadnagara K, Arbuckle S, Lewis D, Wakeland B, Quigg RJ, Ransom RF, Wakeland EK, Topham MK, Bazan NG, Mohan C, Hildebrandt F, Bakkaloglu A, Huang CL, Attanasio M. J Am Soc Nephrol 24: 377-384, 2013). DGKepsilon is unrelated to the complement pathway, which suggests that unidentified pathogenic mechanisms independent of complement dysregulation may result in TMA. Studying Dgke knockout mice may help to understand the pathogenesis of this disease, but no glomerular phenotype has been described in these animals so far. Here we report that Dgke null mice present subclinical microscopic anomalies of the glomerular endothelium and basal membrane that worsen with age and develop glomerular capillary occlusion when exposed to nephrotoxic serum. We found that induction of cyclooxygenase-2 and of the proangiogenic prostaglandin E2 are impaired in Dgke null kidneys and are associated with reduced expression of the antithrombotic cell adhesion molecule platelet endothelial cell adhesion molecule-1/CD31 in the glomerular endothelium. Notably, prostaglandin E2 supplementation was able to rescue motility defects of Dgke knockdown cells in vitro and to restore angiogenesis in a test in vivo. Our results unveil an unexpected role of Dgke in the induction of cyclooxygenase-2 and in the regulation of glomerular prostanoids synthesis under stress. PMID- 26887832 TI - NLRP3 deletion protects against renal fibrosis and attenuates mitochondrial abnormality in mouse with 5/6 nephrectomy. AB - Progressive fibrosis in chronic kidney disease (CKD) is the well-recognized cause leading to the progressive loss of renal function. Emerging evidence indicated a pathogenic role of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in mediating kidney injury. However, the role of NLRP3 in the remnant kidney disease model is still undefined. The present study was undertaken to evaluate the function of NLRP3 in modulating renal fibrosis in a CKD model of 5/6 nephrectomy (5/6 Nx) and the potential involvement of mitochondrial dysfunction in the pathogenesis. Employing NLRP3(+/+) and NLRP3(-/-) mice with or without 5/6 Nx, we examined renal fibrotic response and mitochondrial function. Strikingly, tubulointerstitial fibrosis was remarkably attenuated in NLRP3(-/-) mice as evidenced by the blockade of extracellular matrix deposition. Meanwhile, renal tubular cells in NLRP3(-/-) mice maintained better mitochondrial morphology and higher mitochondrial DNA copy number, indicating an amelioration of mitochondrial abnormality. Moreover, NLRP3 deletion also blunted the severity of proteinuria and CKD-related hypertension. To further evaluate the direct role of NLRP3 in triggering fibrogenesis, mouse proximal tubular cells (PTCs) were subjected to transforming growth factor beta1 (TGF-beta1), and the cellular phenotypic changes were detected. As expected, TGF-beta1-induced alterations of PTC phenotype were abolished by NLRP3 small interfering RNA, in line with a protection of mitochondrial function. Taken together, NLRP3 deletion protected against renal fibrosis in the 5/6 Nx disease model, possibly via inhibiting mitochondrial dysfunction. PMID- 26887831 TI - Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs. AB - : In thick ascending limbs (THALs), nitric oxide (NO) decreases NaCl reabsorption via cGMP-mediated inhibition of Na-K-2Cl cotransporter (NKCC2). In angiotensin (ANG II)-induced hypertension, endothelin-1 (ET-1)-induced NO production by THALs is impaired. However, whether this alters NO's natriuretic effects and the mechanisms involved are unknown. In other cell types, ANG II augments phosphodiesterase 5 (PDE5)-mediated cGMP degradation. We hypothesized that NO mediated inhibition of NKCC2 activity and stimulation of cGMP synthesis are blunted via PDE5 in ANG II-induced hypertension. Sprague-Dawley rats were infused with vehicle or ANG II (200 ng.kg-1.min-1) for 5 days. ET-1 reduced NKCC2 activity by 38 +/- 13% (P < 0.05) in THALs from vehicle-treated rats but not from ANG II-hypertensive rats (Delta: -9 +/- 13%). A NO donor yielded similar results as ET-1. In contrast, dibutyryl-cGMP significantly decreased NKCC2 activity in both vehicle-treated and ANG II-hypertensive rats (control: Delta-44 +/- 15% vs. ANG II: Delta-41 +/- 10%). NO increased cGMP by 2.08 +/- 0.36 fmol/MUg protein in THALs from vehicle-treated rats but only 1.06 +/- 0.25 fmol/MUg protein in ANG II hypertensive rats (P < 0.04). Vardenafil (25 nM), a PDE5 inhibitor, restored NO's ability to inhibit NKCC2 activity in THALs from ANG II-hypertensive rats (Delta: 60 +/- 9%, P < 0.003). Similarly, NO's stimulation of cGMP was also restored by vardenafil (vehicle-treated: 1.89 +/- 0.71 vs. ANG II-hypertensive: 2.02 +/- 0.32 fmol/MUg protein). PDE5 expression did not differ between vehicle-treated and ANG II-hypertensive rats. We conclude that NO-induced inhibition of NKCC2 and increases in cGMP are blunted in ANG II-hypertensive rats due to PDE5 activation. Defects in the response of THALs to NO may enhance NaCl retention in ANG II induced hypertension. PMID- 26887833 TI - Disruption of KCNJ10 (Kir4.1) stimulates the expression of ENaC in the collecting duct. AB - Kcnj10 encodes the inwardly rectifying K(+) channel 4.1 (Kir4.1) and is expressed in the basolateral membrane of late thick ascending limb, distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD). In the present study, we perform experiments in postneonatal day 9 Kcnj10(-/-) or wild type mice to examine the role of Kir.4.1 in contributing to the basolateral K(+) conductance in the CNT and CCD, and to investigate whether the disruption of Kir4.1 upregulates the expression of the epithelial Na(+) channel (ENaC). Immunostaining shows that Kir4.1 is expressed in the basolateral membrane of CNT and CCD. Patch-clamp studies detect three types of K(+) channels (23, 40, and 60 pS) in the basolateral membrane of late CNT and initial CCD in wild-type (WT) mice. However, only 23- and 60-pS K(+) channels but not the 40-pS K(+) channel were detected in Kcnj10(-/-) mice, suggesting that Kir.4.1 is a key component of the 40-pS K(+) channel in the CNT/CCD. Moreover, the depletion of Kir.4.1 did not increase the probability of finding the 23- and 60-pS K(+) channel in the CNT/CCD. We next used the perforated whole cell recording to measure the K(+) reversal voltage in the CNT/CCD as an index of cell membrane potential. Under control conditions, the K(+) reversal potential was -69 mV in WT mice and -61 mV in Kcnj10(-/-) mice, suggesting that Kir4.1 partially participates in generating membrane potential in the CNT/CCD. Western blotting and immunostaining showed that the expression of ENaCbeta and ENaCgamma subunits from a renal medulla section of Kcnj10(-/-) mice was significantly increased compared with that of WT mice. Also, the disruption of Kir4.1 increased aquaporin 2 expression. We conclude that Kir4.1 is expressed in the CNT and CCD and partially participates in generating the cell membrane potential. Also, increased ENaC expression in medullary CD of Kcnj10(-/-) mice is a compensatory action in response to the impaired Na(+) transport in the DCT. PMID- 26887835 TI - Lack of Association of ST-T Wave Abnormalities to Congenital Heart Disease in Neonates. AB - BACKGROUND: ST-T wave (STTW) abnormalities have been described in 20-40% of normal newborns. We sought to describe the associations of these Electrocardiogram (ECG) abnormalities to perinatal course and congenital heart disease (CHD). METHODS: A retrospective chart review was performed on all neonatal ECGs between January 2008 and March 2013 identified from electronic medical records. Electronic medical records were reviewed for perinatal course and maternal medical conditions. Neonates <37 weeks gestation, >3 days age, requiring hemodynamic support in the first 3 days, with oxygen saturation <90% on room air, or with arrhythmias and significant abnormalities of axis and voltage were excluded from the analysis. ST segment elevation or depression of >2 mm in at least one lead and flat or inverted T waves in at least one lead except aVR were considered abnormal. Statistical relationships were explored between STTW abnormalities, perinatal variables and CHD. RESULTS: ECGs were performed on 1043 neonates, of which 664 were included. STTW abnormalities were found in 236 (35.5%) neonates. T wave abnormalities were identified in 191 (28.7%), ST segment abnormalities in 77 (11.6%) and both on 32 (4.8%) neonates. No relationship was found between the ECG abnormalities and perinatal variables, except maternal cefazolin administration during labor. Noncritical CHD was diagnosed by echocardiography in 59/84; STTW abnormalities were seen in 17/59 (29%) patients with and 9/25 (34%) without noncritical CHD, P = .6. CONCLUSION: STTW abnormalities on ECG are commonly found in 35.5% of normal neonates and do not predict noncritical CHD. PMID- 26887836 TI - [Clinical manifestations of 5 patients with idiopathic paroxysmal kinesigenic choreoathetosis]. AB - Paroxysmal kinesigenic choreoathetosis (PKC) is a rare disorder characterized by recurrent and brief attacks of choreoathetoid and/or dystonic movements in trunk and limbs triggered by initiation of voluntary movement. Of 5 patients with idiopathic PKC in our hospital, four were men and one was with family history. Age of onset ranged from 8 to 15 years old. They were consistent with previous reports in the characteristics of involuntary movements, normal neurological findings, normal laboratory data, no abnormal findings of standard imaging studies, and good restraining effects on attacks with carbamazepine. Individual body parts where attacks often involved were different among 5 patients. Although previous reports which said the prognosis and outcome of PKC were good, neuropsychological examinations in our study revealed that 2 patients out of 5 had certain cortical dysfunction, one patient was with progressive deterioration, and the other was with underlying mild abnormalities. Detailed and serial neuropsychological examinations might be necessary for some PKC patients. PMID- 26887837 TI - [Intracerebral hemorrhage associated with nephrotic syndrome-Prevalemce and clinical characteristics]. AB - Of the 11,161 cases of stroke observed for over 9 years, 21 cases in which both levels of serum albumin and cholesterol were < 3 g/dl and > 250 mg/dl, respectively, were identified. Out of these 21 cases, cases of severe proteinuria, i.e., nephrotic syndrome were selected. These included 10 cases of arterial ischemic thrombosis, 2 cases of cerebral venous sinus thrombosis, and 4 cases of intracerebral hemorrhage. The incidence of intracerebral hemorrhage associated with nephrotic syndrome was 0.18% of total stroke or 0.036% intracerebral hemorrhage. Nephrotic syndrome essentially induced a hypercoagulable state. The 4 cases with intracerebral hemorrhage associated with nephrotic syndrome, however, had strong risk factors for intracerebral hemorrhage, suggesting that they overcame the risk for thrombophilia. The diseases associated with the nephrotic syndrome were diabetic nephropathy and amyloidosis in 3 cases and in 1 case, respectively. The nephrotic syndrome tends to be associated with a risk for venous or arterial thrombosis. In addition, we must pay attention to intracerebral hemorrhage associated with nephrotic syndrome in cases of stroke. PMID- 26887834 TI - Mechanism of increased clearance of glycated albumin by proximal tubule cells. AB - Serum albumin is the most abundant plasma protein and has a long half-life due to neonatal Fc receptor (FcRn)-mediated transcytosis by many cell types, including proximal tubule cells of the kidney. Albumin also interacts with, and is modified by, many small and large molecules. Therefore, the focus of the present study was to address the impact of specific known biological albumin modifications on albumin-FcRn binding and cellular handling. Binding at pH 6.0 and 7.4 was performed since FcRn binds albumin strongly at acidic pH and releases it after transcytosis at physiological pH. Equilibrium dissociation constants were measured using microscale thermophoresis. Since studies have shown that glycated albumin is excreted in the urine at a higher rate than unmodified albumin, we studied glucose and methylgloxal modified albumins (21 days). All had reduced affinity to FcRn at pH 6.0, suggesting these albumins would not be returned to the circulation via the transcytotic pathway. To address why modified albumin has reduced affinity, we analyzed the structure of the modified albumins using small angle X-ray scattering. This analysis showed significant structural changes occurring to albumin with glycation, particularly in the FcRn-binding region, which could explain the reduced affinity to FcRn. These results offer an explanation for enhanced proximal tubule-mediated sorting and clearance of abnormal albumins. PMID- 26887838 TI - An open framework for automated chemical hazard assessment based on GreenScreen for Safer Chemicals: A proof of concept. AB - GreenScreen(r) for Safer Chemicals is a framework for comparative chemical hazard assessment. It is the first transparent, open and publicly accessible framework of its kind, allowing manufacturers and governmental agencies to make informed decisions about the chemicals and substances used in consumer products and buildings. In the GreenScreen(r) benchmarking process, chemical hazards are assessed and classified based on 18 hazard endpoints from up to 30 different sources. The result is a simple numerical benchmark score and accompanying assessment report that allows users to flag chemicals of concern and identify safer alternatives. Although the screening process is straightforward, aggregating and sorting hazard data is tedious, time-consuming, and prone to human error. In light of these challenges, the present work demonstrates the usage of automation to cull chemical hazard data from publicly available internet resources, assign metadata, and perform a GreenScreen(r) hazard assessment using the GreenScreen(r) "List Translator." The automated technique, written as a module in the Python programming language, generates GreenScreen(r) List Translation data for over 3000 chemicals in approximately 30 s. Discussion of the potential benefits and limitations of automated techniques is provided. By embedding the library into a web-based graphical user interface, the extensibility of the library is demonstrated. The accompanying source code is made available to the hazard assessment community. Integr Environ Assess Manag 2017;13:167-176. (c) 2016 SETAC. PMID- 26887839 TI - A cost and economic evaluation of the Leeds personality disorder managed clinical network-A service and commissioning development initiative. AB - In the UK, patients with personality disorders presenting complex needs frequently experience an unhelpful pattern of acute treatment followed by community care-with associated high cost implications for services. With UK mental health resources under severe pressure, this leaves commissioners with difficult decisions to make. Yet studies on cost-effectiveness in respect of personality disorder treatment are scarce, particularly for treatments taking place outside of major teaching hospitals in the USA. This paper studies the benefits of an intensive, holistic approach and finds that the Network achieved substantial reductions in health care usage and expenditure in the short to medium term. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887840 TI - ydfD encodes a novel lytic protein in Escherichia coli. AB - Bacteria carry a number of genes that cause cell growth arrest or cell lysis upon expression. Notably, defective prophages retain many lysis proteins. Here, we identified a novel lytic gene, ydfD, on the Qin prophage segment of the Escherichia coli genome. YdfD lyses 99.9% of cells within 2 h of its induction. The co-expression of the upstream gene, dicB, encoding a cell division inhibitor, as well as sulA, encoding another cell division inhibitor, abolished YdfD-induced cell lysis. These results imply that YdfD-induced lysis is a cell division dependent event. We further found that by deleting the hydrophobic 22-residue N terminal domain, the resulting 42-residue C-terminal domain was still toxic to cause cell lysis. We propose that YdfD, associated with the cytoplasmic membrane, inhibits an essential cellular process(s). PMID- 26887841 TI - Experimental evidence for proteins constituting virion components and particle morphogenesis of bacteriophage ZF40. AB - Bacteriophage ZF40 is the only currently available, temperate Myoviridae phage infecting the potato pathogen Pectobacterium carotovorum subsp. carotovorum. Despite its unusual tail morphology, its major tail sheath and tube proteins remained uncharacterized after the initial genome annotation. Using ESI tandem mass-spectrometry, 24 structural proteins of the ZF40 virion were identified, with a sequence coverage ranging between 15.8% and 87.8%. The putative function of 16 proteins could be elucidated based on secondary structure analysis and conservative domain searches. The experimental annotation of 35% of the encoded gene products within the structural region of the genome represents a complete view of the virion structure, which can serve as the basis for future structural analysis as a model phage. PMID- 26887842 TI - A topological approach unveils system invariances and broken symmetries in the brain. AB - Symmetries are widespread invariances underscoring countless systems, including the brain. A symmetry break occurs when the symmetry is present at one level of observation but is hidden at another level. In such a general framework, a concept from algebraic topology, namely, the Borsuk-Ulam theorem (BUT), comes into play and sheds new light on the general mechanisms of nervous symmetries. The BUT tells us that we can find, on an n-dimensional sphere, a pair of opposite points that have the same encoding on an n - 1 sphere. This mapping makes it possible to describe both antipodal points with a single real-valued vector on a lower dimensional sphere. Here we argue that this topological approach is useful for the evaluation of hidden nervous symmetries. This means that symmetries can be found when evaluating the brain in a proper dimension, although they disappear (are hidden or broken) when we evaluate the same brain only one dimension lower. In conclusion, we provide a topological methodology for the evaluation of the most general features of brain activity, i.e., the symmetries, cast in a physical/biological fashion that has the potential to be operationalized. (c) 2016 Wiley Periodicals, Inc. PMID- 26887843 TI - Relationship between the Infant Feeding Preferences of Chinese Mothers' Immediate Social Network and Early Breastfeeding Cessation. AB - BACKGROUND: The relationship between support from members of a mother's social network and breastfeeding continuation is receiving increased attention. OBJECTIVES: The objectives of this study were to describe the infant feeding preferences of Chinese mothers' immediate social network and to examine the association between these preferences and early breastfeeding cessation. METHODS: In total, 1172 mother-infant pairs were recruited from 4 public hospitals in Hong Kong and followed prospectively for 12 months or until breastfeeding stopped. RESULTS: Over 40% of participants' partners preferred breastfeeding and half had no infant feeding preference. Only about 20% of participants' mothers or mothers in-law preferred breastfeeding, and less than 10% reported that all of the 3 significant family members (partner, mother, and mother-in-law) preferred breastfeeding. The partner's preference for infant formula or mixed feeding (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.43-4.71) or having no preference (OR, 1.64; 95% CI, 1.16-2.30) was strongly associated with higher odds of stopping breastfeeding before 1 month. For every additional family member who preferred breastfeeding, the odds of stopping breastfeeding was reduced by almost 20% (OR, 0.81; 95% CI, 0.68-0.97). However, living with a parent-in-law (OR, 1.45; 95% CI, 1.02-2.07) was also a predictor of early breastfeeding cessation. Knowing someone who had breastfed for >= 1 month (OR, 0.64; 95% CI, 0.42-0.97) or having been breastfed as a child (OR, 0.67; 95% CI, 0.45-0.98) significantly lowered the odds of early breastfeeding cessation. CONCLUSIONS: The infant feeding preferences of mothers' immediate social network are significantly associated with breastfeeding continuation. Prenatal breastfeeding education programs should involve significant family members to promote breastfeeding. PMID- 26887844 TI - Use of Donor Human Milk and Maternal Breastfeeding Rates: A Systematic Review. AB - The number of human milk banks is growing worldwide. The introduction of donor human milk (DHM) to neonatal units has been advocated as a strategy to promote maternal breastfeeding. However, concern has been raised that the introduction of DHM may actually lead to a decrease in maternal breastfeeding. To address this question, we conducted a systematic literature review of studies that assessed maternal breastfeeding rates before and after the introduction of DHM. We searched 7 electronic databases, carried out citation tracking, and contacted experts in the field. Where data for breastfeeding rates before and after the introduction of DHM were directly comparable, a relative risk was calculated. Our search identified 286 studies, of which 10 met the inclusion criteria. Definitions of patient populations and study outcomes varied, limiting meaningful comparison. Where possible, relative risks (RR) were calculated on aggregated data. The introduction of DHM had a significant positive impact on any breastfeeding on discharge (RR, 1.19; 95% confidence interval [CI], 1.06-1.35;P= .005) but none on exclusive maternal breastfeeding on discharge (RR, 1.12; 95% CI, 0.91-1.40;P= .27) or on exclusive administration of own mother's milk (OMM) days 1 to 28 of life (RR, 1.08; 95% CI, 0.78-1.49; P= .65). A single-center study demonstrated a significant decrease in the percentage of feeds that were OMM after the introduction of DHM. In conclusion, the available data demonstrate some evidence of positive and negative effects on measures of maternal breastfeeding when DHM is introduced to a neonatal unit. PMID- 26887845 TI - Impact of operation timing on post-operative infections following colorectal cancer surgery. AB - BACKGROUND: To investigate the impact of operation timing on post-operative infections in a cohort of patients undergoing colorectal cancer surgery. METHODS: We prospectively analysed surgical outcomes in patients who underwent colorectal cancer surgery at the First Affiliated Hospital, College of Medicine, Zhejiang University, from January to December in 2014. In this non-randomized trial, patients were divided into three groups according to the surgery start time: CT1 (07:00 to 12:00 h), CT2 (12:01 to 18:00 h), and CT3 (18:01 h to midnight). The primary outcome was the proportion of patients developing infections within 4 weeks of the surgical procedure. RESULTS: Out of 756 patients that were enrolled in the study, 118 developed post-operative infections. The results from blood and pus culture showed 97.1% specimen as being pathogen-free. The overall incidence of post-operative infection was 14.5% (38 of 262), 15.3% (46 of 300) and 17.5% (34 of 194) in the CT1, CT2 and CT3 group, respectively, with no significant inter-group differences. However, white blood cell counts, C-reactive protein and glucose levels at 24 h after the surgical procedure showed significant differences between the three groups (one-way ANOVA, P < 0.05). CONCLUSION: The occurrence of post-operative infection in patients undergoing colorectal cancer surgery was not associated with operation timing. The expression of several inflammatory markers, such as white blood cell counts, C-reactive protein and blood glucose levels tended to correlate with the surgery start time. PMID- 26887846 TI - High-throughput microfluidic device for single cell analysis using multiple integrated soft lithographic pumps. AB - The ability to accurately control fluid transport in microfluidic devices is key for developing high-throughput methods for single cell analysis. Making small, reproducible changes to flow rates, however, to optimize lysis and injection using pumps external to the microfluidic device are challenging and time consuming. To improve the throughput and increase the number of cells analyzed, we have integrated previously reported micropumps into a microfluidic device that can increase the cell analysis rate to ~1000 cells/h and operate for over an hour continuously. In order to increase the flow rates sufficiently to handle cells at a higher throughput, three sets of pumps were multiplexed. These pumps are simple, low-cost, durable, easy to fabricate, and biocompatible. They provide precise control of the flow rate up to 9.2 nL/s. These devices were used to automatically transport, lyse, and electrophoretically separate T-Lymphocyte cells loaded with Oregon green and 6-carboxyfluorescein. Peak overlap statistics predicted the number of fully resolved single-cell electropherograms seen. In addition, there was no change in the average fluorescent dye peak areas indicating that the cells remained intact and the dyes did not leak out of the cells over the 1 h analysis time. The cell lysate peak area distribution followed that expected of an asynchronous steady-state population of immortalized cells. PMID- 26887847 TI - A comparison of heterosexual and LGBTQ cancer survivors' outlooks on relationships, family building, possible infertility, and patient-doctor fertility risk communication. AB - PURPOSE: Little research about cancer-related infertility has examined the experiences and needs of lesbian, gay, bisexual, transgender, or queer (LGBTQ) cancer survivors. This research seeks to understand how LGBTQ survivors are similar to or different from heterosexual survivors with respect to cancer treatments' effects on relationships, plans for parenthood, and fertility preservation decision making. METHODS: Semi-structured telephone interviews conducted with adolescent or young adult (AYA) cancer survivors (n = 56) were coded for themes. Interviews consisted of questions about pre- and post-diagnosis thoughts about relationships, parenthood, possible infertility, and how information about fertility risks was received. RESULTS: While LGBTQ (n = 22) and heterosexual (n = 34) survivors reported similar challenges when dating post diagnosis, heterosexual survivors were more likely to report fertility concerns as affecting romantic relationships (p < .05). LGBTQ survivors seemed more open to raising non-biological children or not becoming a parent than heterosexual survivors. LGBTQ survivors generally reported being satisfied with or indifferent to the information that they were given regarding fertility loss, despite reporting receiving similar amounts of information as compared to heterosexual patients (p < .10). CONCLUSIONS: LGBTQ patients' views on relationships, parenthood, and family building seemed to result in less distress when faced with infertility. However, interventions facilitating information exchange about dating, fertility risks, and family building options may be valuable to LGBTQ and heterosexual cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: LGBTQ cancer survivors may display more adaptive coping with respect to relationships and fertility loss. Oncology professionals may want to proactively introduce positive coping strategies to reduce distress among AYA cancer survivors at risk for infertility. PMID- 26887848 TI - Corrigendum: Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment. PMID- 26887850 TI - Seqotron: a user-friendly sequence editor for Mac OS X. AB - BACKGROUND: Accurate multiple sequence alignment is central to bioinformatics and molecular evolutionary analyses. Although sophisticated sequence alignment programs are available, manual adjustments are often required to improve alignment quality. Unfortunately, few programs offer a simple and intuitive way to edit sequence alignments. RESULTS: We present Seqotron, a sequence editor that reads and writes files in a wide variety of sequence formats. Sequences can be easily aligned and manually edited using the mouse and keyboard. The program also allows the user to estimate both phylogenetic trees and distance matrices. CONCLUSIONS: Seqotron will benefit researchers who need to manipulate and align complex sequence data. Seqotron is a Mac OS X compatible open source project and is available from Github https://github.com/4ment/seqotron/. PMID- 26887849 TI - In-line three-dimensional holography of nanocrystalline objects at atomic resolution. AB - Resolution and sensitivity of the latest generation aberration-corrected transmission electron microscopes allow the vast majority of single atoms to be imaged with sub-Angstrom resolution and their locations determined in an image plane with a precision that exceeds the 1.9-pm wavelength of 300 kV electrons. Such unprecedented performance allows expansion of electron microscopic investigations with atomic resolution into the third dimension. Here we report a general tomographic method to recover the three-dimensional shape of a crystalline particle from high-resolution images of a single projection without the need for sample rotation. The method is compatible with low dose rate electron microscopy, which improves on signal quality, while minimizing electron beam-induced structure modifications even for small particles or surfaces. We apply it to germanium, gold and magnesium oxide particles, and achieve a depth resolution of 1-2 A, which is smaller than inter-atomic distances. PMID- 26887851 TI - Protein aggregation and membrane lipid modifications under lactic acid stress in wild type and OPI1 deleted Saccharomyces cerevisiae strains. AB - BACKGROUND: Lactic acid is a versatile chemical platform with many different industrial applications. Yeasts have been demonstrated as attractive alternative to natural lactic acid producers since they can grow at low pH, allowing the direct purification of the product in the desired acidic form. However, when very high concentrations of organic acids are reached, the major limitation for a viable production is the toxic effect of the product. The accumulation in the cytosol of H(+) and of the weak organic counter-anions triggers a cellular reprogramming. Here, the effects of lactic acid exposure on Saccharomyces cerevisiae have been evaluated by Fourier transform infrared (FTIR) microspectroscopy. In addition to -omic techniques, describing these responses in terms of systems and networks, FTIR microspectroscopy allows a rapid acquisition of the cellular biochemical fingerprint, providing information on the major classes of macromolecules. RESULTS: FTIR analyses on Saccharomyces cerevisiae cells under lactic acid stress at low pH revealed some still uncharacterized traits: (1) a direct correlation between lactic acid exposure and a rearrangement in lipid hydrocarbon tails, together with a decrease in the signals of phosphatidylcholine (PC), one of the main components of cell membrane; (2) a rearrangement in the cell wall carbohydrates, including glucans and mannans (3) a significant yet transient protein aggregation, possibly responsible for the observed transient decrease of the growth rate. When repeated on the isogenic strain deleted in OPI1, encoding for a transcriptional repressor of genes involved in PC biosynthesis, FTIR analysis revealed that not only the PC levels were affected but also the cell membrane/wall composition and the accumulation of protein aggregates, resulting in higher growth rate in the presence of the stressing agent. CONCLUSIONS: This work revealed novel effects evoked by lactic acid on cell membrane/wall composition and protein aggregation in S. cerevisiae cells. We consequently demonstrated that the targeted deletion of OPI1 resulted in improved lactic acid tolerance. Considering that stress response involves many and different cellular networks and regulations, most of which are still not implemented in modelling, these findings constitute valuable issues for interpreting cellular rewiring and for tailoring ameliorated cell factories for lactic acid production. PMID- 26887852 TI - Epidermal Growth Factor Receptor Mutation Status and Treatment Outcome for R0 Resected Patients with Stage 3 Non-small Cell Lung Cancer. AB - BACKGROUND: This study aimed to investigate the association of epidermal growth factor receptor (EGFR) mutation status with treatment outcome for patients with stage 3 non-small cell lung cancer (NSCLC) who had undergone a complete (R0) resection. METHODS: The study identified 3445 NSCLC patients tested for EGFR mutations between September 2001 and December 2011 at the Sun Yat-Sen University Cancer Center. Of these patients, 224 were stage 3 patients who had undergone R0 resections. RESULTS: These 224 R0-resected, pathologic stage 3A and 3B patients included 150 patients with wild-type EGFR and 74 patients with EGFR mutations. During a median follow-up period of 42 months (range, 4-133 months), pathologic stage was shown to be the only prognostic factor. The 3-year overall survival (OS) rates did not differ significantly from the OS rates for the wild-type and mutant EGFR groups (62.0 vs 67.2 %; p = 0.789). Multivariate analyses indicated that the patients in the mutant EGFR group with EGFR exon 19 mutations had a better OS rate (73.0 vs 61.1 %; p = 0.026). CONCLUSIONS: Cancer stage remained the significant prognostic factor in R0-resected stage 3 NSCLC patients. The presence of an EGFR mutation is more likely to be a predictive marker for the response to treatment with tyrosine kinase inhibitors. In the EGFR mutant group, the patients with an exon 19 mutation had better 3-year OS rates. These findings might be considered in future study designs. PMID- 26887853 TI - Role of Extended Thromboprophylaxis After Abdominal and Pelvic Surgery in Cancer Patients: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Abdominopelvic cancer surgery increases the risk of postoperative venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) thromboprophylaxis is recommended, and the role of extended thromboprophylaxis (ETP) is controversial. We performed a systematic review to determine the effect of ETP on deep vein thrombosis (DVT), pulmonary embolism (PE), major bleeding, and all-cause mortality after abdominal or pelvic cancer surgery. METHODS: A search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was undertaken, and studies were included if they compared extended duration (2-6 weeks) with conventional duration of thromboprophylaxis (2 weeks or less) after cancer surgery. Pooled relative risk (RR) was estimated using a random effects model. RESULTS: Seven randomized and prospective studies were included, comprising 4807 adult patients. ETP was associated with a significantly reduced incidence of all VTEs [2.6 vs. 5.6 %; RR 0.44, 95 % confidence interval (CI) 0.28 0.70, number needed to treat (NNT) = 39] and proximal DVT (1.4 vs. 2.8 %; RR 0.46, 95 % CI 0.23-0.91, NNT = 71). There was no statistically significant difference in the incidence of symptomatic PE (0.8 vs. 1.3 %; RR 0.56, 95 % CI 0.23-1.40), major bleeding (1.8 vs. 1.0 %; RR 1.19, 95 % CI 0.47-2.97), and all cause mortality (4.2 vs. 3.6 %; RR 0.79, 95 % CI 0.47-1.33). None of the outcomes differed if randomized trials were analyzed independently. CONCLUSIONS: ETP after abdominal or pelvic surgery for cancer significantly decreased the incidence of all VTEs and proximal DVTs, but had no impact on symptomatic PE, major bleeding, or 3-month mortality. ETP should be routinely considered in the setting of abdominal and pelvic surgery for cancer patients. PMID- 26887854 TI - Association Between Socio-Demographic Background and Self-Esteem of University Students. AB - The purpose of this study was to scrutinize self-esteem of university students and explore association of self-esteem with academic achievement, gender and other factors. A sample of 346 students was selected from Punjab University, Lahore Pakistan. Rosenberg self-esteem scale with demographic variables was used for data collection. Besides descriptive statistics, binary logistic regression and t test were used for analysing the data. Significant gender difference was observed, self-esteem was significantly higher in males than females. Logistic regression indicates that age, medium of instruction, family income, student monthly expenditures, GPA and area of residence has direct effect on self-esteem; while number of siblings showed an inverse effect. PMID- 26887855 TI - Abuse of Gabapentin is Associated with Opioid Addiction. AB - The objective of this study was to evaluate the extent of gabapentin misuse in a dually diagnosed correctional population, and to evaluate if this abuse is specific to the presence of an opioid use disorder (OUD). Two-hundred and fifty former inmates, living in a correctional community center, who were referred for a psychiatric evaluation, were asked, through a brief written questionnaire, whether or not they used the following drugs for non-medical use in the past: opiates, gabapentin, buproprion, quetiapine, and fluoxetine. The average age of this population was 37.2 +/- 12.1 years (n = 250). Sixty-four percent were male, 72 % were white, 27 % were black, and 1 % was Hispanic. All patients had substance use disorders, the large majority (72 %) to more than one substance. Fifty-eight percent had an opioid use disorder, again mostly in combination with other drugs and/or alcohol. Depressive disorders and attention deficit hyperactivity disorder were the most common psychiatric conditions. Sixty-two percent of patients reported prescription drug misuse of any kind. As expected, a high percent (55 %) reported opiate misuse. No patient reported fluoxetine misuse. Sixteen percent reported having misused gabapentin in the past. Of patients with an opioid use disorder (OUD: n = 145), 26 % endorsed gabapentin abuse while only 4 % of patients without an OUD (n = 105) endorsed the non medical use of gabapentin. This difference was highly statistically significant (Chi square chi2 = 21.6, p < 0.0001). A growing concern about gabapentin misuse was supported in this study: 26 percent of opiate addicted patients reported illegally obtaining, overusing, or malingering problems to obtain gabapentin. This study highlights the fact that gabapentin abuse appears specific to an opioid addicted population. PMID- 26887857 TI - Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization. AB - We investigate the adhesion and molecular organization of the plasma membrane of T lymphocytes interacting with a surrogate antigen presenting cell comprising glass supported ordered arrays of antibody (alpha-CD3) nano-dots dispersed in a non-adhesive matrix of polyethylene glycol (PEG). The local membrane adhesion and topography, as well as the distribution of the T cell receptors (TCRs) and the kinase ZAP-70, are influenced by dot-geometry, whereas the cell spreading area is determined by the overall average density of the ligands rather than specific characteristics of the dots. TCR clusters are recruited preferentially to the nano-dots and the TCR cluster size distribution has a weak dot-size dependence. On the patterns, the clusters are larger, more numerous, and more enriched in TCRs, as compared to the homogeneously distributed ligands at comparable concentrations. These observations support the idea that non-ligated TCRs residing in the non-adhered parts of the proximal membrane are able to diffuse and enrich the existing clusters at the ligand dots. However, long distance transport is impaired and cluster centralization in the form of a central supramolecular cluster (cSMAC) is not observed. Time-lapse imaging of early cell surface contacts indicates that the ZAP-70 microclusters are directly recruited to the site of the antibody dots and this process is concomitant with membrane adhesion. These results together point to a complex interplay of adhesion, molecular organization and activation in response to spatially modulated stimulation. PMID- 26887856 TI - Electroconvulsive Therapy in Women: A Retrospective Study from a Mental Health Hospital in Turkey. AB - The aim was to evaluate the clinical profile and effectiveness of ECT in women. A retrospective chart review was carried out to identify female patients who had received ECT during the period September 2013-February 2015. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. The total number of patients, admitted to our psychiatry inpatient clinic during the survey period, was 802. During this period, 26 (3.24 %) female patients received ECT. Patients who received ECT were mostly in age group of 25-44 years (76.9 %). Twenty percent of patients were in the postpartum period. Psychotic disorders (46.1 %) was the most common diagnosis for which ECT was used, followed by bipolar affective disorder, current episode manic (19.2 %). At the end of ECT courses, 70 % of the patients showed good response with a CGI-I of 1 or 2, and 30 % showed minimal response with a CGI-I score of 3. The most common side effects were post-ECT confusion (15.4 %) and prolonged seizure (11.5 %). This rate of prolonged seizure was higher the rates reported in the literature. The bronchospasm related with remifentanil, post-ECT bradycardia, hypertensive crisis and oligohydramnios were also reported in one case each. ECT is a safe and effective treatment option in women with severe psychiatric disorders and disorders in the perinatal/postpartum period are a major area of ECT use. The female gender may be a contributing factor for the higher rates of prolonged seizure. PMID- 26887858 TI - Autosomal recessive retinitis pigmentosa with homozygous rhodopsin mutation E150K and non-coding cis-regulatory variants in CRX-binding regions of SAMD7. AB - The aim of this study was to unravel the molecular pathogenesis of an unusual retinitis pigmentosa (RP) phenotype observed in a Turkish consanguineous family. Homozygosity mapping revealed two candidate genes, SAMD7 and RHO. A homozygous RHO mutation c.448G > A, p.E150K was found in two affected siblings, while no coding SAMD7 mutations were identified. Interestingly, four non-coding homozygous variants were found in two SAMD7 genomic regions relevant for binding of the retinal transcription factor CRX (CRX-bound regions, CBRs) in these affected siblings. Three variants are located in a promoter CBR termed CBR1, while the fourth is located more downstream in CBR2. Transcriptional activity of these variants was assessed by luciferase assays and electroporation of mouse retinal explants with reporter constructs of wild-type and variant SAMD7 CBRs. The combined CBR2/CBR1 variant construct showed significantly decreased SAMD7 reporter activity compared to the wild-type sequence, suggesting a cis-regulatory effect on SAMD7 expression. As Samd7 is a recently identified Crx-regulated transcriptional repressor in retina, we hypothesize that these SAMD7 variants might contribute to the retinal phenotype observed here, characterized by unusual, recognizable pigment deposits, differing from the classic spicular intraretinal pigmentation observed in other individuals homozygous for p.E150K, and typically associated with RP in general. PMID- 26887859 TI - The Validation of a Spanish Version of the Multidimensional Inventory of Religious/Spiritual Well-Being in Mexican College Students. AB - After the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB) was validated as a reliable instrument for the Western European context it is primarily intended in this study to translate the measure into Spanish and adapt it for the Mexican culture. Furthermore we investigate whether spirituality/religiosity has a similar impact on indicators of personality and subjective well-being in Mexico as it does in samples drawn from Western European cultures. 190 students (99 females) from public and private universities in Guadalajara, all Mexican citizens, were involved in this study. We found strong evidential support for the six factor solution of the Original MI-RSWB in this Mexican population. By mirroring previous research the measure showed a highly satisfying internal consistency (alpha = .91 for the total score and .75 or higher for all six sub dimensions). Furthermore the total RSWB score was observed to be related with Eysenck's personality dimensions Extraversion (r = .24, p < .01), and Psychoticism (r = -.28, p < .001), although not with Neuroticism. There was also a positive correlation with Sense of Coherence (r = .31, p < .001). In conclusion, the dimensionality of RSWB and its associations with personality and subjective well-being was well supported in this first application within a Mexican cultural context. PMID- 26887861 TI - Exposure to a 50-Hz magnetic field induced ceramide generation in cultured cells. AB - Purpose To investigate the effects of a 50-Hz magnetic field (MF) exposure on ceramide metabolism, as well as the cascade downstream signaling pathways in human amniotic (FL) cells. Materials and methods FL cells were exposed to MF at 0.4 mT for different durations (from 5-60 min). The ceramides levels were analyzed with high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The activity of cathepsin D was assayed using a fluorometric assay kit, and the activity of protein phosphatase 2A (PP2A) was examined by Western blotting. After exposing to MF at 0.4 mT for 60 min with sequential culture for different durations (0, 3, 6, 12 or 36 h), the rate of cell apoptosis was assessed by flow cytometry. Results Exposing cells to MF at 0.4 mT for different durations caused a significant increase in ceramide production via de novo synthesis and hydrolysis of sphingomyelin (SM), and the effect was different according to the exposure time. However, no significant change in cell apoptosis was detected after MF exposure for 60 min with sequentially culturing for up to 36 h. In addition, increase in ceramide did not activate its downstream signal molecules, cathepsin D and PP2A, which are usually closely related to apoptosis of cells. Conclusions Exposure to a 50-Hz MF could raise ceramide levels but had no significant effect on apoptosis in cultured cells. PMID- 26887860 TI - Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice. AB - Follicular helper T (Tfh) cells provide crucial help to germinal center B (GCB) cells for proper antibody production, and a specialized subset of regulatory T cells, follicular regulatory T (Tfr) cells, modulate this process. However, Tfr cell function in the GC is not well understood. Here, we define Tfr cells as a CD4(+) Foxp3(+) CXCR5(hi) PD-1(hi) CD25(low) TIGIT(high) T-cell population. Furthermore, we have used a novel mouse model ("Bcl6FC") to delete the Bcl6 gene in Foxp3(+) T cells and thus specifically deplete Tfr cells. Following immunization, Bcl6FC mice develop normal Tfh- and GCB-cell populations. However, Bcl6FC mice produce altered antigen-specific antibody responses, with reduced titers of IgG and significantly increased IgA. Bcl6FC mice also developed IgG antibodies with significantly decreased avidity to antigen in an HIV-1 gp120 "prime-boost" vaccine model. In an autoimmune lupus model, we observed strongly elevated anti-DNA IgA titers in Bcl6FC mice. Additionally, Tfh cells from Bcl6FC mice consistently produce higher levels of Interferon-gamma, IL-10 and IL-21. Loss of Tfr cells therefore leads to highly abnormal Tfh-cell and GCB-cell responses. Overall, our study has uncovered unique regulatory roles for Tfr cells in the GC response. PMID- 26887862 TI - Short Communication: Persistence of HIV Antibody Avidity in the Presence of Antiretroviral Therapy. AB - The effects of antiretroviral therapy (ART) on the performance of HIV incidence assays have been well documented. To improve upon current assay approaches or focus the development of future assays, studies are needed to characterize the effects of ART on all candidate HIV incidence assays. In this study, we compared the performance of three antibody avidity-based HIV incidence assays, the Limiting Antigen (LAg), Bio-Rad Avidity, and HIV-1 Multiplex assays, using a well defined cohort of recent HIV-1 seroconverters composed of ART-naive HIV-1 infected individuals and those who received ART early or delayed in the course of infection. Differences in the performance of all three avidity-based incidence assays were noted with study subjects who received ART. The LAg assay and Multiplex total antibody measurements (nMFI) exhibited similar kinetics in reactivity, as these assays tended to fluctuate with changes in viral load. In the early ART group, all seven subjects remained recent by both assays at time points >1 year postseroconversion, and assay values declined dramatically postdelayed ART initiation. In contrast, the two-well, antibody-dissociation avidity assays, Bio-Rad Avidity and Multiplex avidity index (AI) measurements, continued to mature in the early ART group, although blunted relative to the ART naive group, and assay values remained stable after delayed ART initiation. In summary, although the HIV incidence assays evaluated in this study are all designed to measure antibody avidity, each assay is affected differently by ART induced virus suppression, presumably because of the distinct assay formats and procedures for measuring avidity. PMID- 26887863 TI - Emerging role of lipid droplets in Aedes aegypti immune response against bacteria and Dengue virus. AB - In mammals, lipid droplets (LDs) are ubiquitous organelles that modulate immune and inflammatory responses through the production of lipid mediators. In insects, it is unknown whether LDs play any role during the development of immune responses. We show that Aedes aegypti Aag2 cells - an immune responsive cell lineage - accumulates LDs when challenged with Enterobacter cloacae, Sindbis, and Dengue viruses. Microarray analysis of Aag2 challenged with E.cloacae or infected with Dengue virus revealed high transcripts levels of genes associated with lipid storage and LDs biogenesis, correlating with the increased LDs numbers in those conditions. Similarly, in mosquitoes, LDs accumulate in midgut cells in response to Serratia marcescens and Sindbis virus or when the native microbiota proliferates, following a blood meal. Also, constitutive activation of Toll and IMD pathways by knocking-down their respective negative modulators (Cactus and Caspar) increases LDs numbers in the midgut. Our results show for the first time an infection-induced LDs accumulation in response to both bacterial and viral infections in Ae. Aegypti, and we propose a role for LDs in mosquito immunity. These findings open new venues for further studies in insect immune responses associated with lipid metabolism. PMID- 26887864 TI - The current role of Gamma Knife radiosurgery in the management of intracranial haemangiopericytoma. AB - BACKGROUND: Haemangiopericytomas (HPCs) are rare tumours characterised by aggressive behaviour with tendency to local recurrence and to metastasise. WHO grade II and grade III tumours show different progression-free survival and overall survival rates. Gross total tumour resection is still considered the treatment of choice. Adjuvant radiation therapies represent an option in the treatment strategy regardless the extent of resection. Based on this consideration, Gamma Knife radiosurgery has been introduced either as a primary treatment or as an adjuvant treatment for residual or recurrent tumours. METHOD: A systematic search was performed on PubMed, Web of Science and Google Scholar for clinical series reporting Gamma Knife radiosurgery, Cyberknife and Linear Accelerator (LINAC) for the management of intracranial HPCs. RESULTS: Fourteen studies focusing on the effects of Gamma Knife radiosurgery for intracranial HPCs were included. Four studies reported data on Cyberknife radiosurgery and LINAC. A total of 208 patients harbouring 366 tumours have been reported. Patient's features, radiosurgical treatment characteristics and follow-up data of the pertinent literature have been critically revised. CONCLUSIONS: Gamma Knife radiosurgery and the other radiosurgical techniques represent a feasible and effective therapy in the management of HPCs. Tumour control and survival rate are comparable to those reported for radiotherapy. Further studies should be focused to define the exact role of Gamma Knife radiosurgery in the management of HPCs. PMID- 26887865 TI - Association of mental health disorders and Medicaid with ED admissions for ambulatory care-sensitive condition conditions. AB - INTRODUCTION: Adult Medicaid enrollees are more likely to have mental health disorders (MHDs) than privately insured patients and also have high rates of emergency department (ED) visits for ambulatory care-sensitive conditions (ACSCs). We aimed to evaluate the association of MHD and insurance type with ED admissions for ACSC in the United States. METHODS: We conducted a cross-sectional study of ED visits made by adults aged 18 to 64 years using the corrected 2011 National Emergency Department Survey. Using multivariable logistic regression analysis, we controlled for sociodemographics and clinical variables to determine the association between insurance type, MHD, Medicaid, and MHD (as an interaction variable) and ED admissions for ACSC. RESULTS: There were 131 million ED visits in 2011; after exclusions, 1.4 million admissions were included in our study. Of all ED visits, 44.7% had an MHD, of which 49.9% were covered by Medicaid and 38.1% were covered by private insurance. A total of 32.6% (95% confidence interval, 32.5%-32.7%) of ED admissions were for an ACSC. Medicaid-covered ED visits were more likely to result in ACSC hospital admission (odds ratio, 1.32; 95% confidence interval, 1.30-1.35) compared with visits covered by private insurance. Among patients with MHD, those with Medicaid insurance had 1.6 times the odds of ACSC admission compared with those privately insured. CONCLUSION: Among all ED admissions, patients covered by Medicaid are more likely to be admitted for an ACSC when compared with those covered by private insurance, with a larger association being present among patients with MHD comorbidities. PMID- 26887867 TI - Persistent perceptual grouping effects in the evaluation of simple arithmetic expressions. AB - Landy and Goldstone (2007a, 2010) demonstrated that an explicit rule, operator precedence for simple arithmetic expressions, is enforced in part by perceptual processes like unit formation and attention. When perceptual grouping competes with operator precedence, errors increase. We replicated this result (Exp. 1) and investigated whether perceptual grouping effects persist when the visual stimulus is presented briefly and then masked (Exp. 2) and when verbal recoding is encouraged through vocal expression (Exp. 3). We found that perceptual-grouping effects persisted in the masking condition, suggesting that the mental representations of arithmetic expressions retain visuospatial characteristics. Similarly, verbalization of the expressions did not eliminate perceptual-grouping effects, suggesting that participants were not verbally recoding. In sum, the persistent effects of unit formation and spatial attention emphasize the importance of perceptual processing in the development of human expertise in this domain. PMID- 26887869 TI - [Expert consensus on the diagnosis and management of intrauterine adhesions in China]. PMID- 26887870 TI - [Application of laparoscopic surgery on gynecologic malignancies]. PMID- 26887868 TI - Caveolae Restrict Tiger Frog Virus Release in HepG2 cells and Caveolae-Associated Proteins Incorporated into Virus Particles. AB - Caveolae are flask-shaped invaginations of the plasma membrane. Caveolae play important roles in the process of viruses entry into host cells, but the roles of caveolae at the late stage of virus infection were not completely understood. Tiger frog virus (TFV) has been isolated from the diseased tadpoles of the frog, Rana tigrina rugulosa, and causes high mortality of tiger frog tadpoles cultured in Southern China. In the present study, the roles of caveolae at the late stage of TFV infection were investigated. We showed that TFV virions were localized with the caveolae at the late stage of infection in HepG2 cells. Disruption of caveolae by methyl-beta-cyclodextrin/nystatin or knockdown of caveolin-1 significantly increase the release of TFV. Moreover, the interaction between caveolin-1 and TFV major capsid protein was detected by co-immunoprecipitation. Those results suggested that caveolae restricted TFV release from the HepG2 cells. Caveolae-associated proteins (caveolin-1, caveolin-2, cavin-1, and cavin 2) were selectively incorporated into TFV virions. Different combinations of proteolytic and/or detergent treatments with virions showed that caveolae associated proteins were located in viral capsid of TFV virons. Taken together, caveolae might be a restriction factor that affects virus release and caveolae associated proteins were incorporated in TFV virions. PMID- 26887871 TI - [Summary of the first conference of the twelfth editorial board of Chinese Journal of Obstetrics and Gynecology]. PMID- 26887872 TI - [Long-term oncological outcomes after laparoscopic versus abdominal radical hysterectomy in stage I a2- II a2 cervical cancer: a matched cohort study]. AB - OBJECTIVE: To investigate the long- term oncological outcomes of laparoscopic radical hysterectomy (LRH) plus lymph node dissection (LND) and abdominal radical hysterectomy (ARH) plus LND for patients with stage Ia2-IIa2 cervical cancer. METHODS: A retrospective review of stage Ia2- II a2 cervical cancer patients who underwent LRH + LND (n=372) and ARH + LND (n=434) at the First Affiliated Hospital of Sun Yat- sen University from Jan. 2005 to Aug. 2013 was performed. Individual patient matching was performed by the risk factors for recurrence [tumor size, lymph vascular space invasion (LVSI), depth of cervical stromal invasion, lymph node metastasis, parametrial involvement, and resection margin involvement] between two groups. After matched, a total of 203 patient pairs (LRH ARH) were enrolled. The survival data, surgery data, intraoperative and postoperative complications were compared between the two groups. To assess the prognosis factors, the univariate and multivariate Cox's proportional hazards model analysis were conducted. Stratified analysis was performed based on the independent prognosis factors to investigate the survival data between the two surgery groups. RESULTS: (1) Surgery data: The operating time [(239+/-44) vs (270+/-42) minutes], estimated blood loss [(210+/-129) vs (428+/-320) ml], the duration of bowel motility return [(2.0+/-0.8) vs (3.0+/-1.6) days] and hospital stay [(11+/-6) vs (13+/-6) days] in the LRH group were significantly shorter than those in ARH group (all P<0.01). (2) Intraoperative and postoperative complications: The intraoperative complications rate was similar betweentwo groups [6.4%(13/203) vs 6.9%(14/203), P=1.000]. The rate of postoperative complications (excluded bladder dysfunction) in the LRH group were significantly lower than those in the ARH group [9.4% (19/203) vs 20.2% (41/203), P=0.002]. While there was no significant difference in the rates of bladder dysfunction between two groups [36.5% (74/203) vs 37.4% (76/203), P=0.910]. (3) Recurrence and survival data: There was no significant difference in the recurrence rates between the LRH group and ARH groups [7.9% (16/203) vs 9.4% (19/203), P=0.850]. There were similar 5-year recurrence-free survival (RFS; 92.1% vs 91.1%, P=0.790) and 5-year overall survival (OS; 93.7% vs 96.1%, P=0.900). (4) Prognosis factor: In univariate analysis, the results showed that tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, LVSI, stromal invasion, parametrium invasion, pelvic lymph node metastasis, and para aortic lymph node metastasis were significantly associated with poor prognosis (all P<0.01). However, age, body mass index (BMI), surgery type, histological type, grade were not significantly associated with poor prognosis (all P>0.05). The multivariate analysis results, showed that tumor size, pelvic lymph node metastasis,and para- aortic lymph node metastasis were significantly associated with poor prognosis (all P<0.01). Stratified analysis showed that, even in patients with tumor size >4 cm, pelvic lymph node metastasis positive, and para aortic lymph node metastasis positive in all subgroups, there were not significant difference for the estimated 5-year RFS and 5-year OS between LRH and ARH group (all P>0.05). CONCLUSION: For patients with stage Ia2-IIa2 cervical cancer, LRH plus lymph node dissection is an oncologically safe and surgical feasible alternative to ARH. PMID- 26887873 TI - [Comparison of the short-term and long-term outcomes after laparoscopic surgery for early-stage endometrial cancer]. AB - OBJECTIVE: To evaluate the short- term and long- term outcomes after laparoscopic surgery compared with traditional laparotomy in patients with stage I-II endometrial cancer. METHODS: A retrospective study of population among 673 patientsfor early-stage endometrial cancer between Jan. 2007 and May 2014 was involved from 6 third-grade class-A communal hospitals in Guangxi. Three hundred and seventy-six cases were performed by laparoscopy, 297 cases by laparotomy. The t-test and chi(2) test was used to compare the short-term and long-term outcomes. The short-term outcomes including surgical related outcomes and operative complications, the long- term outcomes including quality of life (pelvic floor functions and sexual functions), survival analysis and recurrence. The International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Sympotom (ICIQ- FLUTS) and the Female Sexual Function Index (FSFI) were used to assess pelvic floor function and sexual function. Survival rates were estimated by Kaplan-Meier analysis. The survival curves were compared by log-rank test. Cox regression analysis was used to select the risk factors for prognosis. RESULTS: (1) The short-term outcomes: There were significant difference in operative time [(258+/-71) vs (226+/-69) minutes], estimated blood loss [(343+/- 211) vs (491+/-411) ml], anus exhausting time [(2.3+/-0.9) vs (2.9+/-1.0) days], preserved days of installing catheter [(7 +/- 5) vs (10+/-8) days], post- operative length of stay [(12 +/- 7) vs (18 +/- 12) days] between laparoscopic group andlaparotomy group (all P <0.05). While, there was no significant difference in lymph nodes yielded (21+/-8 vs 21+/-11; P>0.05),the intra-operative complications occurred [8.5%(32/376) vs 10.4%(31/297); P>0.05], and the post operative complications [18.1% (68/376) vs 22.2% (66/297); P>0.05] between laparoscopic group and laparotomy group. However, the complications of vascular injury and the poor wound healing in laparoscopic group were respectively lower than those in laparotomy group [1.9%(7/376) vs 5.4% (16/297), P=0.003; and 0.3% (1/376) vs 4.7% (14/297), P<0.01]. (2) The long- term outcomes: There were no significant differences in overall survival (OS) and the degree of incontinence in ICIQ-FLUTS questionnaire between the two groups (all P >0.05). The sexual desire and sexual satisfaction scores dimension after 12 months of post- operative in FSFI questionnaire in the laparoscopic group were higher than those in laparotomy group (all P <0.05). However, there were no significant differences in sexual arousal, vaginal lubrication, orgasm and sexual pain dimension scores between the two groups (all P >0.05). The recurrence rate was 12.0%(45/376) in laparoscopic group and 14.5%(43/297) in laparotomy group (P= 0.269). The 5-year OS was 89.5% in the laparoscopic group and 87.2% in the open group (P >0.05) , and the 5-year free-progression survival rate was 87.9% in the laparoscopic group and 85.1% in the open group (P >0.05). (3) Prognostic factors in laparoscopic group: The univariate analysis shown that pathological type, surgical pathological staging, deep myometrial invasion, and retroperitoneal lymph node positive were significantly affected prognosis in laparoscopic group (all P<0.01). The multivariate analyses showed that pathological type and surgical pathological stage were the independent prognostic factors (all P<0.01). CONCLUSIONS: Laparoscopy could reduce estimated blood loss, accelerate postoperative recovery and improve the quality of life after surgery compared to laparotomy, also ensure the same oncologically results as that by laparotomy. So, laparoscopic approach is a safe and effective treatment method for early- stage endometrial cancer. PMID- 26887874 TI - [Value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia cases with uterine mass]. AB - OBJECTIVE: To evaluate the value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia (GTN) cases with uterine mass. METHODS: The clinical characteristics of patients underwent laparoscopic surgery for a suspected diagnosis of GTN with uterine mass in Peking Union Medical College Hospital from November 2009 to November 2014 were retrospectively reviewed and analyzed. GTN and other pregnant-related disease were definitely diagnosed by pathological findings. The prognoses of the GTN cases were also investigated. RESULTS: Sixty-two patients with a suspected diagnosis of GTN with uterine mass were studied. Among them, 17 cases were definitely diagnosed as GTN, including 8 choriocarcinoma, 5 invasive mole and 4 placental site trophoblastic tumor (PSTT). The other 45 cases were diagnosed as benign pregnancy-related diseases, including 29 cornual pregnancy, 6 cesarean scar pregnancy, 5 placenta accreta, 4 intramural uterine pregnancy and 1 exaggerated placental site. There were no significantly differences between the two groups in average age, preoperative value or tendency of beta-hCG, and location or size of lesions (P>0.05). More GTN patients showed a history of hydatidiform mole [5/17 vs 4% (2/45) , P>0.05], and more patients with benign pregnancy-related disease showed a history of cesarean section [38% (17/45) vs 1/17, P>0.05]. No serious perioperative complication was found in these patients received laparoscopic surgery. All GTN patients achieved complete remission by chemotherapy later. Except for 1 case loss, no recurrence was found in 11 low-risk stage I cases with an average follow-up period of 11- 66 months, 1 high-risk stage I case with a follow-up period of 61 months and 4 cases PSTT with a follow-up period of 13-66 months. CONCLUSIONS: There were some atypical GTN cases with uterine mass, which were difficult to be differentiated from benign pregnancy-related diseases according to the clinical characteristics. Laparoscopic surgery with a pathologic diagnosis could be an essential way with efficiency and safety. PMID- 26887876 TI - [Pay attention to the basic and clinicopathologic research of perineural invasion of cervical cancer]. PMID- 26887875 TI - [Comparison of safety and efficacy of laparoscopic versus abdominal radical hysterectomy in the treatment of patients with stage I a2-II b cervical cancer]. AB - OBJECTIVE: To compare the safety and efficacy after laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in the treatment of patients with stage I a2-II b cervical cancer. METHODS: In a retrospective study, data were analyzed from patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ia2-II b cervical cancer underwent LRH or ARH at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; First Affiliated Hospital, School of Medicine, Shihezi University; and the Guizhou Provincial People's Hospital between 2000 and 2015. Perioperative outcomes and survival analysis were compared. RESULTS: (1) The FIGO stages, histotypes, metastasis of lymph nodes, lymph vascular space invasion and neoadjuvant chemotherapy significantly differed between the LRH group and the ARH group (all P<0.05). In order to eliminate the effects by the unbalanced data, stratified analysis was conducted based on FIGO stage. There were 861 patients in stage I a2-I b1 group, including 663 patients in LRH group and 198 patients in ARH group. And there were 668 patients in stage I b2-IIb group, including 389 patients in LRH group and 279 patients in ARH group. (2) In the patients with stage I a2- I b1 and I b2- II b tumor, there were no significant difference in age, histotype, differentiation degree, parametrial invasion, lymphvasular invasion space and neoadjvant chemotherapy between the LRH group and the ARH group (all P>0.05). For patients with stage I a2- I b1, the operation time in the LRH group was longer than that in the ARH group (P=0.027), and it showed less blood loss and lower blood transfusion rate in the LRH group than those in the ARH group (all P=0.000). The findings were similar in the patients with stage I b2-II b (all P=0.000). (3) There were no significant difference in intraoperative complications and postoperative complications between the LRH and the ARH group in the patients with stage I a2-I b1 and I b2-IIb, respectively (all P>0.05). (4) The median follow- up time was 24 months (range: 1 to 177 months), the recurrence rate was 3.6% (38/1 052) in LRH group and 3.1% (15/477) in ARH group,there was not significant difference (P>0.05). The estimated 3- year overall survival (OS) and the free-progression survival time (PFS) were respectively 92.4% and 91.5% in LRH group, and 91.8% and 91.5% in ARH group. There was no significant difference in the overall survival (P=0.738) or progress free survival (P=0.990) by log-rank test. Moreover, there were no significant difference in OS or PFS between the LRH group and the ARH group in patients with stage I a2- I b1 and I b2- II b, respectively (all P>0.05). CONCLUSION: LRH is safe and effective, and it could be used a routine way for the treatment of patients with stage I a2-IIb cervical cancer. PMID- 26887877 TI - [Analysis of serum lipids levels and the establishment of reference intervals for serum lipids in middle and late pregnancy]. AB - OBJECTIVE: To explore the serum lipids levels in healthy pregnant women, and to establish the reference intervals of serum lipids in middle and late pregnancy. METHODS: Triglyceride (TG), total cholesterol (TCH), high density lipoprotein (HDL), low density lipoprotein (LDL), apo-lipoprotein-A(APO-A) and apo lipoprotein-B (APO-B) were measured in 3 200 pregnant women and 3 200 healthy women of childbearing age(the control group) from January 2014 to Febuary 2015 in Obstetrics and Gynecology Hospital of Fudan University. In the healthy pregnant women, serum lipids were measured at 14-20, 24-28 and 37-40 gestational weeks, respectively. All the parameters were detected by Hitachi 7180 automatic biochemical analyzer. The test results were calculated and determined by the C28 A3 standard of the National Clinical and Laboratory Standards Institute. And the normal reference intervals of serum lipids in middle and late pregnancy were defined as 2.5%-97.5%. RESULTS: (1) The levels of TG, TCH, HDL, LDL, APO-A and APO-B in the control group were 0.8, 4.2, 1.0, 2.7 mmol/L and 1.1, 0.8 g/L, respectively. The levels of TG, TCH, HDL, LDL, APO-A and APO-B in middle and late pregnancy were significantly higher than those in the control group (P<0.05). (2) The serum lipids levels at 14-20, 24-28 and 37-40 gestational weeks in healthy pregnant women were compared with the control group as following. The TG levels were 1.9, 3.8 and 4.4 folds of the control group; the TCH levels were 1.1, 1.5 and 1.5 folds of the control group; the HDL levels were 1.2, 1.6 and 1.5 folds of the control group; the LDL levels were 1.1, 1.4 and 1.4 folds of the control group; the APO-A levels were 1.3, 1.4 and 1.5 folds of the control group; and the APO-B levels were 1.1, 1.5 and 1.5 fold of the control group respectively. The TG level was the most increased, and it increased gradually with gestational age (P<0.01). (3) The median of LDL to HDL cholesterol ratio in the healthy pregnancy group at 14-20, 24-28 and 37-40 gestational weeks were 2.7, 2.5, 2.6, respectively, which were significantly lower than that of the control group (2.8; P<0.05). (4) Reference intervals of serum lipids at 14-20, 24-28 and 37-40 gestational weeks in healthy pregnant women were as following. The TG levels were 0.7-3.9, 1.7-6.3 and 1.6-8.1 mmol/L, respectively; the TCH were 3.3-6.9, 4.3-8.3, 4.3-8.7 mmol/L, respectively; the HDL were 0.8-1.8, 1.0-2.1 and 1.0-2.1 mmol/L, respectively; the LDL were 2.1-4.5, 2.7-5.1 and 2.6-5.2 mmol/L, respectively; the APO-A were 1.1-1.8, 1.2-1.9 and 1.1-2.4 g/L, respectively; and the APO-B were 0.6 1.4, 0.9-1.8 and 0.8-2.1 g/L, respectively. The LDL/HDL ratios were 2.3-3.1, 2.2 2.9 and 2.1-3.0, respectively. CONCLUSIONS: Serum lipids increased physiologically with gestational age in middle and late pregnancy. The establishment of reference intervals for serum lipids in pregnancy will help to distinguish abnormal serum lipid levels in middle and late pregnancy. PMID- 26887878 TI - [Analysis of risk factors for adverse perinatal outcomes in women with pancytopenia]. AB - OBJECTIVE: To explore the pregnancy outcomes of women with pancytopenia and the risk factors for the adverse perinatal outcomes. METHODS: A total of 106 pregnant women with pancytopenia were admitted to Peking University People's Hospital from Jan. 2005 to Sep. 2014. The clinical data and the pregnancy outcomes were reviewed retrospectively to investigate the risk factors for the adverse perinatal outcomes. RESULTS: (1 ) Eighty-four patients were found pancytopenia before pregnancy while 22 were found for the first time during pregnancy. Sixty four patients were diagnosed as aplastic anemia; 30 as myelodysplastic syndrome; 2 as paroxysmal nocturnal hemoglobinuria; 4 as hypersplenism, and 1 as anti phospholipid syndrome. Diagnoses of the remaining 5 patients were uncertain. (2) Sixty-nine patients received at least one time blood transfusion before delivery. (3) As for the complications, nine women developed gestational diabetes; twenty two suffered severe preeclampsia (SPE); two were diagnosed as anemic heart disease and three experienced respiratory tract infection. The postpartum blood loss ranged from 50 ml to 3 800 ml, with the median of 400 ml. And six women had the blood loss more than 1 000 ml. The gestational age at delivery ranged from 24 weeks to 40 weeks, with the median of 37.0 weeks. (4) Thirty-one patients suffered adverse perinatal outcomes, including 3 cases of intrauterine death, 4 therapeutic labor induction before 28 gestational weeks, 6 premature delivery before 34 weeks. There were 2 neonates complicated with intracranial hemorrhage, 2 with neonatal respiratory distress syndrome, 3 with hypoxic-ischemic encephalopathy, 2 with severe asphyxia and death, and 14 with small for gestational age. Among the patients with adverse perinatal outcomes, 26 women received blood transfusion during pregnancy and 17 developed SPE. The maximum and the minimum value of their white cell count (WBC), hemoglobin concentration (Hb) and blood platelet count (BPC) were (4.9+/-1.4)*10(9)/L, (2.9+/-0.8)*10(9)/L, (88.6+/-14.9) g/L, (57.9+/-14.5) g/L, (47.7+/-27.4)*10(9)/L and (11.9+/ 12.3)*10(9)/L, respectively. For those patients without adverse perinatal outcomes, 43 received blood transfusion during pregnancy and 5 developed SPE. The maximum and the minimum value of their WBC, Hb and BPC were (5.2+/-1.5)*10(9)/L, (3.2+/-0.9)*10(9)/L, (101.4+/-16.2) g/L, (71.9 +/- 14.5) g/L, (52.3 +/- 24.0) * 10(9)/L and (19.0+/-12.1) * 10(9)/L, respectively. The multivariate regression analyses indicated that SPE, Hb less than 70 g/L and BPC less than 20*10(9)/L were the independent risk factors for the poor perinatal outcomes in pregnant women with pancytopenia (P<0.05). CONCLUSIONS: The incidence of adverse perinatal complications increased dramatically in pregnant women with pancytopenia. Concurrent SPE, minimum Hb less than 70 g/L and minimum BPC less than 20 * 10(9)/L may be the independent risk factors for the adverse perinatal outcomes. PMID- 26887879 TI - [Continuous improvement of portable domestic pelvic floor neuromuscular electrical stimulation on the pelvic floor function of patients with urinary incontinence]. AB - OBJECTIVE: To evaluate continuous improvement of portable domestic pelvic floor neuromuscular electrical stimulation on the pelvic floor function of patients with stress urinary incontinence after short-term pelvic floor electrophysiological treatment in hospital. METHODS: Totally 60 women with stress urinary incontinence were recruited for this randomized controlled trial. The control group including a total of 30 patients, only received 4 weeks pelvic floor electrophysiological treatment in the hospital. Family consolidation treatment group (experimental group) including 30 patients, after 4-week treatment in hospital, received 12-week of pelvic floor neuromuscular electrical stimulation using portable electrical stimulator at home under the guidance of doctors. In post-treatment 6 months and 9 months, 1-hour pad test was measured for urine leakage, pelvic floor electrical physiological parameters were assessed, and subjective improvement of symptoms of urinary incontinence were evaluated. All these data were analysed to compare the effect of the two groups. RESULTS: In 9 months after treatment, average change of urine leakage, the control group and experiment group were (75+/-24)% versus (99+/-3)%, the difference was statistically significant (P<0.01). In the experiment group, strength of type I muscle (4.4+/-0.7), strength of type II muscle (4.8+/-0.4) and pelvic floor dynamic pressure [(96+/-12) cmH(2)O, 1 cmH(2)O=0.098 kPa] were better than those of control group [3.2+/-1.0, 4.3+/-0.9, (86+/-10) cmH(2)O, respectively], the differences were statistically significant (P<0.01). Subjective outcome, the control group and experiment group were (6.5+/-2.9) versus (1.8+/-1.7), subjective outcome between the two groups had significant difference (P<0.01). CONCLUSION: After short-term pelvic floor electrophysiological treatment in hospital, the portable domestic pelvic floor neuromuscular electrical stimulation in patients with stress urinary incontinence is helpful to continuous improvement of pelvic floor function. PMID- 26887880 TI - Extramedullary plasmacytoma of the gingiva. PMID- 26887881 TI - Management of a severe case of Gitelman syndrome with poor response to standard treatment. AB - Gitelman syndrome is an autosomal recessive distal renal tubular disorder caused by defective sodium chloride transporters. Biochemically, it presents with hypokalaemic metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is usually managed with oral potassium supplements and potassium-sparing diuretics. We report a case of a 28-year-old woman whose condition worsened during pregnancy; she became resistant to standard management after delivery of her second child. She was managed in a specialist metabolic clinic through a comprehensive approach including perseverance with oral potassium supplement, weekly intravenous potassium and magnesium infusion, correction of vitamin D level and the offering of appropriate dietary advice; this controlled the patient's symptoms and prevented repeated hospital admissions. In this case report, we illustrate a patient's presentation and diagnosis with Gitelman syndrome, discuss triggers of exacerbation, review the relevant literature in terms of differential diagnoses and provide practical advice on the management of difficult cases in a specialist clinic. PMID- 26887882 TI - Anterior subtalar dislocation with comminuted fracture of the anterior calcaneal process. AB - Anterior subtalar dislocation is a very rare injury. We report a case of an 81 year-old woman who had her right foot injured during a motor vehicle accident. Radiographs showed anterior subtalar dislocation with comminuted fracture of the anterior calcaneal process. The dislocation was closely reduced and protected by a short leg cast. One year postinjury, the patient had only mild pain when walking on uneven ground. There was mild tenderness over the lateral heel. Subtalar motion was mildly painful. There was no pain with ankle motion. PMID- 26887884 TI - Coming full circle: an impressive case of Crohn's disease. PMID- 26887883 TI - Childhood-onset eosinophilic granulomatosis with polyangiitis: a rare childhood vasculitis mimicking anthrax and eosinophilic leukaemia. AB - A 14-year-old boy previously misdiagnosed as having cutaneous anthrax was referred with a 2-month history of multiple wide and deep ulceronecrotic lesions in the lower extremities, which occurred after contact with animals. Skin biopsy was compatible with vasculitis. Further examination at our hospital elicited eosinophilia and a history of asthma. On the second day of hospitalisation, he developed deep vein thrombosis. A diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was established and intravenous methylprednisolone was administered. The patient showed remarkable improvement of the cutaneous lesions. Diagnosis of EGPA is challenging in the vasculitic phase and necessitates a detailed history that specifically questions the patient for an asthma background. This case illustrates a severe cutaneous presentation of EGPA and emphasises the difficulty of diagnosis as a result of overlapped signs and symptoms with cutaneous anthrax and leukaemia. EGPA should be kept in mind in the differential diagnosis of cutaneous lesions associated with eosinophilia. PMID- 26887885 TI - Paradoxical reaction to antitubercular treatment in a case of pulmonary tuberculosis. AB - A 51-year-old man presented with intermittent fever, mild cough and loss of appetite of 1-month duration. His sputum smear was positive for acid-fast bacilli and his chest radiograph revealed apical infiltrations. The patient was treated with antitubercular therapy (ATT), recovered and was well for 1 month, after which he suddenly developed focal seizures. MRI of the brain with gadolinium enhancement showed high intensity nodular foci in the frontal, parietal and occipital regions. The patient was diagnosed as a case of paradoxical reaction to ATT, and was successfully managed with continued ATT and adjunctive steroid therapy. PMID- 26887886 TI - Abatacept experience in steroid and rituximab-resistant focal segmental glomerulosclerosis. AB - Primary focal segmental glomerular sclerosis (FSGS), one of the major causes of nephrotic syndrome, eventually results in end-stage renal disease. Currently, FSGS is treated with immunosuppressive therapies, which include calcinuerin inhibitors (cyclosporine), glucocorticoids, B-cell depleting agents (rituximab) and, recently, a T-cell co-stimulatory inhibitor (abatacept). Until recently, there had been no cases reporting resistance to all current therapies. We report a case of a 62-year-old Caucasian man with biopsy-proven FSGS, who responded well to oral prednisolone therapy. However, 2 years later, he had a relapse and failed to respond to prednisolone. Subsequent treatments then included cyclosporine, rituximab and cyclophosphamide, which were not successful. The patient was then administered abatacept, a novel T-cell co-stimulatory inhibitor-though he did not experience any side effects, there was no change in proteinuria nor in creatinine. PMID- 26887888 TI - Inverted hypopyon in the eye. PMID- 26887887 TI - Pseudoacromegaly in pachydermoperiostosis. PMID- 26887889 TI - Synthesis of magnetofluorescence Gd-doped CuInS2/ZnS quantum dots with enhanced longitudinal relaxivity. AB - In this paper, we describe the rapid microwave-assisted synthesis of Gd(3+)-doped CuInS2 (Gd:CIS) quaternary quantum dots (q-dots), which integrate the functions of optical fluorescence and magnetic resonance imaging. Through passivation of ZnS shells around Gd:CIS cores, high-quality and robust photostable Gd:CIS/ZnS core/shell q-dots with enhanced quantum yields were obtained. The intensity and peak-to-peak linewidth of the electron spin resonance (EPR) signal were found to vary depending on the Gd(3+) concentration of Gd:CIS/ZnS. Benefiting from the incorporation of paramagnetic Gd(3+) ions, the formed q-dots exhibited well resolved and strong signals of electron paramagnetic resonance and provided significant contrast enhancement in T1-weighted images owing to the remarkably high longitudinal relaxivity (r1 = 55.90 mM(-1) s(-1)) and low r2/r1 ratio (1.42), which are significantly higher than those of commercially available T1 contrast agents. We expect that this facile one-pot synthetic strategy can be extended to the preparation of other Cu-based sulfide quaternary nanomaterials. PMID- 26887891 TI - Mid-infrared surface transmitting and detecting quantum cascade device for gas sensing. AB - We present a bi-functional surface emitting and surface detecting mid-infrared device applicable for gas-sensing. A distributed feedback ring quantum cascade laser is monolithically integrated with a detector structured from a bi functional material for same frequency lasing and detection. The emitted single mode radiation is collimated, back reflected by a flat mirror and detected by the detector element of the sensor. The surface operation mode combined with the low divergence emission of the ring quantum cascade laser enables for long analyte interaction regions spatially separated from the sample surface. The device enables for sensing of gaseous analytes which requires a relatively long interaction region. Our design is suitable for 2D array integration with multiple emission and detection frequencies. Proof of principle measurements with isobutane (2-methylpropane) and propane as gaseous analytes were conducted. Detectable concentration values of 0-70% for propane and 0-90% for isobutane were reached at a laser operation wavelength of 6.5 MUm utilizing a 10 cm gas cell in double pass configuration. PMID- 26887890 TI - Women in community corrections in New York City: HIV infection and risks. AB - Although the incidence of HIV among women on probation, parole and alternatives to incarceration programs is significant to public health, drivers of this concentrated epidemic among women under community corrections remain understudied. This study examined prevalence of HIV and sexually transmitted infections and the associations between substance use, socio-demographic factors and the prevalence of biologically-confirmed HIV and other sexually transmitted infections among a sample of 337 substance-using women recruited from community correction sites in New York City. Prevalence of HIV was 13% and sexually transmitted infections was 26% ( Chlamydia, trachomatis and Neisseria gonorrhea). After adjusting for covariates, HIV-positive women were 1.42 times more likely to use crack/cocaine than HIV-negative women (95% CI = 1.05-1.92). HIV-positive women were 25% less likely than HIV-negative women to report any unprotected vaginal and anal sex with their main partner (95% CI = 0.57-0.99). They were 70% less likely than HIV-negative women to report unprotected vaginal sex with a non paying casual partner (95% CI = 0.1-0.9) and 22% less likely to report unprotected vaginal sex across all partners (95% CI = 0.61-0.99). Community corrections settings may be optimal venues to launch HIV/sexually transmitted infections prevention that have potential to reach and engage an ever-growing number of substance-using women. PMID- 26887892 TI - Paper trials: a qualitative study exploring the place of portfolios in making revalidation recommendations for Responsible Officers. AB - BACKGROUND: A portfolio of supporting information (SI) reflecting a doctor's entire medical practice is now a central aspect of UK appraisal for revalidation. Medical revalidation, introduced in 2012, is an assessment of a doctor's competence and passing results in a five yearly license to practice medicine. It assesses of a doctor's professional development, workplace performance and reflection and aims to provide assurance that doctors are up-to-date and fit to practice. The dominant assessment mechanism is a portfolio. The content of the revalidation portfolio has been increasingly prescribed and the assessment of the SI is a fundamental aspect of the appraisal process which ultimately allows Responsible Officers (ROs) to make recommendations on revalidation. ROs, themselves doctors, were the first to undergo UK revalidation. This qualitative study explored the perceptions of ROs and their appraisers about the use of this portfolio of evidence in a summative revalidation appraisal. METHODS: 28 purposefully sampled London ROs were interviewed following their revalidation appraisal and 17 of their appraisers participated in focus groups and interviews. Thematic analysis was used to identify commonalities and differences of experience. RESULTS: SI was mostly easy to provide but there were challenges in gathering certain aspects. ROs did not understand in what quantities they should supply SI or what it should look like. Appraisers were concerned about making robust judgements based on the evidence supplied. A lack of reflection from the process of collating SI and preparing for appraisal was noted and learning came more from the appraisal interview itself. CONCLUSIONS: More explicit guidance must be available to both appraisee and appraiser about what SI is required, how much, how it should be used and, how it will be assessed. The role of SI in professional learning and revalidation must be clarified and further empirical research is required to examine how best to use this evidence to make judgments as part of this type of appraisal. PMID- 26887893 TI - Race-based differences in routine cytogenetic profiles of patients with multiple myeloma. PMID- 26887894 TI - Chemical shift assignment of the alternative scaffold protein IscA. AB - The IscA protein (11.5 kDa) is an essential component of the iron sulphur cluster biogenesis machine. In bacteria, the machine components are clustered in operons, amongst which the most important is the isc operon. Bacterial IscA has direct homologues also in eukaryotes. Like the protein IscU, IscA is thought to assist cluster formation as an alternative scaffold protein which receives the cluster before transferring it further to the final acceptors. Several crystal structures have been published. They all report an IscA dimeric form, although the packing of the protomers in the dimers differs amongst structures. No solution studies have currently been reported. Here we report the (1)H, (13)C and (15)N backbone and side-chain chemical shift assignments of the cluster-free E. coli IscA as a starting point for further studies of the structure and functions of this still poorly characterized protein. We show that IscA exists in solution as an equilibrium between different species. Spectrum assignment was thus challenging given the heterogeneous nature of the sample but doable through judicious choice of selective labelling and concentration dependent studies. PMID- 26887895 TI - Reference-free single-pass EPI Nyquist ghost correction using annihilating filter based low rank Hankel matrix (ALOHA). AB - PURPOSE: MR measurements from an echo-planar imaging (EPI) sequence produce Nyquist ghost artifacts that originate from inconsistencies between odd and even echoes. Several reconstruction algorithms have been proposed to reduce such artifacts, but most of these methods require either additional reference scans or multipass EPI acquisition. This article proposes a novel and accurate single-pass EPI ghost artifact correction method that does not require any additional reference data. THEORY AND METHODS: After converting a ghost correction problem into separate k-space data interpolation problems for even and odd phase encoding, our algorithm exploits an observation that the differential k-space data between the even and odd echoes is a Fourier transform of an underlying sparse image. Accordingly, we can construct a rank-deficient Hankel structured matrix, whose missing data can be recovered using an annihilating filter-based low rank Hankel structured matrix completion approach. RESULTS: The proposed method was applied to EPI data for both single and multicoil acquisitions. Experimental results using in vivo data confirmed that the proposed method can completely remove ghost artifacts successfully without prescan echoes. CONCLUSION: Owing to the discovery of the annihilating filter relationship from the intrinsic EPI image property, the proposed method successfully suppresses ghost artifacts without a prescan step. Magn Reson Med 76:1775-1789, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26887896 TI - Tackling the crisis in general practice. PMID- 26887897 TI - Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis. AB - Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the >160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor sigmaA, which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors. PMID- 26887898 TI - Case Report: Resolution of Severe Sexual Aggression in a Developmentally Disabled Adolescent During Leuprolide Acetate Use. PMID- 26887899 TI - The Nature of Secondary Interactions at Electrophilic Metal Sites of Molecular and Silica-Supported Organolutetium Complexes from Solid-State NMR Spectroscopy. AB - Lu[CH(SiMe3)2]3 reacts with [SiO2-700] to give [(=SiO)Lu[CH(SiMe3)2]2] and CH2(SiMe3)2. [(=SiO)Lu[CH(SiMe3)2]2] is characterized by solid-state NMR and EXAFS spectroscopy, which show that secondary Lu...C and Lu...O interactions, involving a gamma-CH3 and a siloxane bridge, are present. From X-ray crystallographic analysis, the molecular analogues Lu[CH(SiMe3)2]3-x[O-2,6-tBu C6H3]x (x = 0-2) also have secondary Lu...C interactions. The (1)H NMR spectrum of Lu[CH(SiMe3)2]3 shows that the -SiMe3 groups are equivalent to -125 degrees C and inequivalent below that temperature, DeltaG(?)(Tc = 148 K) = 7.1 kcal mol( 1). Both -SiMe3 groups in Lu[CH(SiMe3)2]3 have (1)JCH = 117 +/- 1 Hz at -140 degrees C. The solid-state (13)C CPMAS NMR spectrum at 20 degrees C shows three chemically inequivalent resonances in the area ratio of 4:1:1 (12:3:3); the J resolved spectra for each resonance give (1)JCH = 117 +/- 2 Hz. The (29)Si CPMAS NMR spectrum shows two chemically inequivalent resonances with different values of chemical shift anisotropy. Similar observations are obtained for Lu[CH(SiMe3)2]3-x[O-2,6-tBu-C6H3]x (x = 1 and 2). The spectroscopic data point to short Lu...Cgamma contacts corresponding to 3c-2e Lu...Cgamma-Sibeta interactions, which are supported by DFT calculations. Calculated natural bond orbital (NBO) charges show that Cgamma carries a negative charge, while Lu, Hgamma, and Sibeta carry positive charges; as the number of O-based ligands increases so does the positive charge at Lu, which in turns shortens the Lu...Cgamma distance. The change in NBO charges and the resulting changes in the spectroscopic and crystallographic properties show how ligands and surface support sites rearrange to accommodate these changes, consistent with Pauling's electroneutrality concept. PMID- 26887900 TI - Effect of Left Cardiac Sympathetic Denervation on the Electromechanical Window in Patients with either Type 1 or Type 2 Long QT Syndrome: A Pilot Study. AB - BACKGROUND: Left cardiac sympathetic denervation (LCSD) exerts significant antifibrillatory effects in patients with long QT syndrome (LQTS). Recently, electromechanical window (EMW) has emerged as a novel torsadogenic marker in LQTS, superior to QT interval (QTc) in distinguishing symptomatic from asymptomatic patients. OBJECTIVE: To explore the hypothesis that LCSD improves EMW most favorably in patients with LQT1. DESIGN: From September 2006 to July 2015, 44 LQT1 and 25 LQT2 patients underwent LCSD. Subset analysis was performed on the six LQT1 and seven LQT2 patients who had echocardiograms both pre-LCSD and >=3 months post-LCSD. EMW is defined as the time difference (ms) between aortic valve closure and the end of the QT interval, measured from an ECG on the concurrent echocardiogram. RESULTS: Compared to published normal EMW values of 22 +/- 19 ms, pre-LCSD EMW mean values were -78 +/- 36 ms in LQT1 and -71 +/- 35 ms in LQT2 (P < .001). Following LCSD, there was a 57 +/- 35 ms decrease in QTc in LQT1 (P = .16) and 23 +/- 21 ms decrease in QTc in LQT2 (P = .3). Overall, there was a 35 +/- 57 ms mean improvement in EMW post-LCSD (P = .04). Five of the 6 (83%) LQT1 subjects had a favorable EMW change post-LCSD (mean improvement 56 +/- 25 ms, P = .04). Five of the 7 (71%) LQT2 subjects had a favorable EMW change post-LCSD (mean improvement 18 +/- 19 ms, P = .2). CONCLUSIONS: The precise mechanism of the LCSD therapeutic effect in LQTS patients is not fully understood. This pilot study raises the possibility that LCSD's antitorsadogenic effect in patients with LQT1 could be conferred in part by restoration of electromechanical order, evidenced by normalization of the EMW. PMID- 26887901 TI - Diplopia on vorapaxar: An unexpected side effect emerging only at second glance. PMID- 26887902 TI - Hospital at home: home-based end-of-life care. AB - BACKGROUND: The policy in a number of countries is to provide people with a terminal illness the choice of dying at home. This policy is supported by surveys indicating that the general public and people with a terminal illness would prefer to receive end-of-life care at home. This is the fourth update of the original review. OBJECTIVES: To determine if providing home-based end-of-life care reduces the likelihood of dying in hospital and what effect this has on patients' symptoms, quality of life, health service costs, and caregivers, compared with inpatient hospital or hospice care. SEARCH METHODS: We searched the following databases until April 2015: Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library), Ovid MEDLINE(R) (from 1950), EMBASE (from 1980), CINAHL (from 1982), and EconLit (from 1969). We checked the reference lists of potentially relevant articles identified and handsearched palliative care publications, clinical trials registries, and a database of systematic reviews for related trials (PDQ-Evidence 2015). SELECTION CRITERIA: Randomised controlled trials, interrupted time series, or controlled before and after studies evaluating the effectiveness of home-based end-of-life care with inpatient hospital or hospice care for people aged 18 years and older. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality. We combined the published data for dichotomous outcomes using fixed-effect Mantel-Haenszel meta-analysis. When combining outcome data was not possible, we reported the results from individual studies. MAIN RESULTS: We included four trials in this review and did not identify new studies from the search in April 2015. Home-based end-of-life care increased the likelihood of dying at home compared with usual care (risk ratio (RR) 1.33, 95% confidence interval (CI) 1.14 to 1.55, P = 0.0002; Chi(2) = 1.72, df = 2, P = 0.42, I(2) = 0%; 3 trials; N = 652; high quality evidence). Admission to hospital while receiving home-based end-of-life care varied between trials, and this was reflected by a high level of statistical heterogeneity in this analysis (range RR 0.62 to RR 2.61; 4 trials; N = 823; moderate quality evidence). Home-based end-of life care may slightly improve patient satisfaction at one-month follow-up and reduce it at six-month follow-up (2 trials; low quality evidence). The effect on caregivers is uncertain (2 trials; low quality evidence). The intervention may slightly reduce healthcare costs (2 trials, low quality evidence). No trial reported costs to patients and caregivers. AUTHORS' CONCLUSIONS: The evidence included in this review supports the use of home-based end-of-life care programmes for increasing the number of people who will die at home, although the numbers of people admitted to hospital while receiving end-of-life care should be monitored. Future research should systematically assess the impact of home-based end-of-life care on caregivers. PMID- 26887903 TI - Supplementation with multiple micronutrients for breastfeeding women for improving outcomes for the mother and baby. AB - BACKGROUND: Globally, more than two billion people are estimated to be deficient in key vitamins and minerals, particularly iodine, iron and zinc. The majority of these people live in low-income settings and are typically deficient in more than one micronutrient. However, micronutrient deficiency among breastfeeding mothers and their infants also remains an issue in high-income settings, specifically among women who avoid meat and/or milk, women who may lack sufficient supplies of vitamin B12 and vitamin D, and/or women who are iron-deficient. Young children, pregnant and lactating women are particularly vulnerable to micronutrient deficiencies. They not only have a relatively greater need for vitamins and minerals because of their physiological state, but are also more susceptible to the harmful consequences of deficiencies. Multiple-micronutrient supplementation might be an option to solve these problems. OBJECTIVES: The objective of this review was to evaluate the effects of multiple-micronutrient supplementation in breastfeeding mothers on maternal and infant outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials of multiple-micronutrient supplementation of three or more micronutrients versus placebo, no supplementation or supplementation with two or fewer micronutrients, irrespective of dosage of micronutrients, in breastfeeding mothers. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: We found no studies that compared multiple-micronutrient supplementation (with three or more micronutrients) versus supplementation with two or fewer micronutrients.Two small studies (involving a total of 52 women) were included. One study compared multiple micronutrients with placebo and the other study compared multiple micronutrients with a group who received no supplementation. The studies were carried out in Brazil (36 adolescent mothers) and the USA (16 women) and included women with a low socioeconomic status. A lack of information in the study reports meant that risk of bias could not be adequately assessed (unclear risk of bias for many domains). There were no quantitative data for any of this review's outcomes so meta analysis was not possible.Neither of the studies reported on the primary outcomes of interest in this review: maternal morbidity (febrile illness, respiratory tract infection, diarrhoea), adverse effects of micronutrients within three days of receiving the supplement, infant mortality (defined as a child dying before completing the first year of age).One study reported qualitatively on maternal anaemia (a secondary outcome of this review) - the study found that multiple micronutrient supplementation was effective for recuperating from anaemia but there were no data for inclusion in our analyses. Maternal satisfaction was not reported in the included studies. Similarly, none of this review's infant secondary outcomes were reported in the included studies: clinical micronutrient deficiency; morbidity episodes (febrile illness, respiratory tract infection, diarrhoea, other), adverse effects of micronutrients within three days of receiving the supplement. AUTHORS' CONCLUSIONS: We found no evidence to quantitatively assess the effectiveness of multiple-micronutrient supplementation in improving health outcomes in mother and baby. The results of this review are limited by the small numbers of studies available, small sample sizes and the studies not reporting on the outcomes of interest in this review. There is no evidence to evaluate potential adverse effects of multiple-micronutrient supplements, particularly excess dosages.There is a need for high-quality studies to assess the effectiveness and safety of multiple-micronutrient supplementation for breastfeeding women for improving outcomes for the mother and her baby. Further research should focus on whether multiple-micronutrient supplementation during lactation compared with none, a placebo or supplementation with fewer than two micronutrients is beneficial to maternal and infant health outcomes. Future studies should collect data on outcomes beyond micronutrient concentrations, for example: maternal and infant morbidity, adverse effects, maternal satisfaction, the risks of excess supplementation, and potential adverse interactions between the micronutrients and the other outcomes. This would help to bridge the gap between research on intermediary outcomes and health outcomes in order to develop sound policy in this field. Future studies could more precisely assess a variety of multiple-micronutrient combinations and different dosages and look at how these affect maternal and infant health outcomes. Larger studies with longer follow-up would improve the quality of studies and provide stronger evidence. In most of the included studies, bias could not be adequately assessed due to lack of information, therefore attention should be given to adequate methods of randomisation and allocation concealment, adequate methods of blinding of the participants, providers and the outcome assessors to improve the methodological quality of studies in this field. PMID- 26887904 TI - Production of Metal-Free Composites Composed of Graphite Oxide and Oxidized Carbon Nitride Nanodots and Their Enhanced Photocatalytic Performances. AB - A novel metal-free composite (GN) composed of two types of carbon-based nanomaterials, graphite oxide (GO) and 2D oxidized carbon nitride (OCN) nanodots was produced. Chemical and morphological characterizations reveal that GN contains a main component of GO with well-dispersed 2D OCN nanodots. GN shows enhanced photocatalytic performance for degrading an organic pollutant, Rhodamine B, under visible light. PMID- 26887905 TI - How to cope with insufficient pneumoperitoneum and exposure when performing laparoscopic gastric bypass surgery. AB - OBJECTIVE: Despite following international guidelines and conducting routine preoperative dietary counseling, every bariatric surgeon will encounter technical challenges in laparoscopic gastric bypass surgery. We present a series of patients in whom the bariatric procedure was stopped after encountering insufficient exposure during diagnostic laparoscopy. These patients were sent back for dietary counseling and underwent surgery after conservative weight loss. The data from this two-step procedure are analyzed and discussed. METHODS: This concept was applied and studied in 14 patients from a series of 620 bariatric procedures. Patients who underwent a primary laparoscopic gastric bypass (n = 593) were used as references. RESULTS: The patients in the study group were significantly heavier than those in the reference group (165 vs. 127 kg, p < 0.001), with 79 % having a BMI >50 kg/m(2). The patients lost a median of 11 kg after 2 months of conservative treatment, and the mean BMI decreased from 55.7 to 52.6 kg/m(2). All the patients in the study group underwent laparoscopic surgery for the second procedure with no need for conversion. The complication rate was not elevated in the study group. Overall hospital costs were higher for the study group compared with those for the primary laparoscopic bypass group (27,136 vs. 19,601 USD, p = 0.034). CONCLUSION: The primary laparoscopic procedure can be stopped in patients with insufficient exposure instead of having them undergo conversion to open surgery. These patients may undergo successful laparoscopic procedures after conservative weight loss with no increased risk and with all of the possible benefits of a laparoscopic approach. As a result of this study, we have established a fixed, preoperative lower limit of 10 % excess weight reduction before accepting superobese patients (BMI >50 kg/m(2)) for surgery at our hospital. PMID- 26887906 TI - The effects of seasonal training on heart rate and oxygen saturation during face immersion apnea in elite breath-hold diver: a case report. AB - The purpose of the present study was to monitor a diver's ability to perform maximal face-immersion apnea throughout the competitive season. A male, world class apnea diver was followed for 1 year (from March 2012 to March 2013). During this period he was tested six times. Each test session involved the measurements of the pulmonary function and respiratory muscle strength. In addition, the ability to perform maximal face-immersion apnea was also explored. The results of face-immersion apnea durations showed a continuous improvement throughout the preparation period 1 with the peak in the main competition period and a decline during the competition period 2 and the transition period. It seemed that the training periodization was successful by producing the diver's peak performance level at the main diving competition i.e. the 2012 AIDA Freediving World Championships. In conclusion, the study shows that changes in training interventions due to seasonal training periodization could be accompanied by changes in a diver's ability to perform the maximal face-immersion apnea. However, further research is needed to establish the influences of individual components of apnea training on a diver's performance. PMID- 26887907 TI - Bioreducible Fluorinated Peptide Dendrimers Capable of Circumventing Various Physiological Barriers for Highly Efficient and Safe Gene Delivery. AB - Polymeric vectors have shown great promise in the development of safe and efficient gene delivery systems; however, only a few have been developed in clinical settings due to poor transport across multiple physiological barriers. To address this issue and promote clinical translocation of polymeric vectors, a new type of polymeric vector, bioreducible fluorinated peptide dendrimers (BFPDs), was designed and synthesized by reversible cross-linking of fluorinated low generation peptide dendrimers. Through masterly integration all of the features of reversible cross-linking, fluorination, and polyhedral oligomeric silsesquioxane (POSS) core-based peptide dendrimers, this novel vector exhibited lots of unique features, including (i) inactive surface to resist protein interactions; (ii) virus-mimicking surface topography to augment cellular uptake; (iii) fluorination-mediated efficient cellular uptake, endosome escape, cytoplasm trafficking, and nuclear entry, and (iv) disulfide-cleavage-mediated polyplex disassembly and DNA release that allows efficient DNA transcription. Noteworthy, all of these features are functionally important and can synergistically facilitate DNA transport from solution to the nucleus. As a consequences, BFPDs showed excellent gene transfection efficiency in several cell lines (~95% in HEK293 cells) and superior biocompatibility compared with polyethylenimine (PEI). Meanwhile BFPDs provided excellent serum resistance in gene delivery. More importantly, BFPDs offer considerable in vivo gene transfection efficiency (in muscular tissues and in HepG2 tumor xenografts), which was approximately 77-fold higher than that of PEI in luciferase activity. These results suggest bioreducible fluorinated peptide dendrimers are a new class of highly efficient and safe gene delivery vectors and should be used in clinical settings. PMID- 26887908 TI - Protein expression pattern in cerebellum of Cav2.1 mutant, tottering-6j mice. AB - Neuronal voltage-gated Cav2.1 channel controls a broad array of functions, including neurotransmitter release, neuronal excitability, activity-dependent gene expression, and neuronal survival. The Cav2.1 channel is molecular complexes consisting of several subunits: alpha1, alpha2/delta, beta, and gamma. The pore forming subunit, alpha1, is encoded by the Cacna1a gene. Tottering-6j mice, generated by the Neuroscience Mutagenesis Facility at The Jackson Laboratory, are a recessive mutant strain in which the mutation has been chemically induced by ethylnitrosourea. In tottering-6j mice, mutation in the Cacna1a gene results in a base substitution (C-to-A) in the consensus splice acceptor sequence, which results in deletion of a part of the S4-S5 linker, S5, and a part of S5-S6 linker domain I in the alpha1 subunit of Cav2.1 channel. The mice display motor dysfunctions and absence-like seizures. However, protein expression in the cerebellum of tottering-6j mice has not been investigated. Real-time quantitative reverse transcription polymerase chain reaction and histological analyses of the cerebellum of tottering-6j mice revealed high expression levels of tyrosine hydroxylase, zebrin II, and ryanodine receptor 3 compared with those of wild-type mice. Conversely, a low level of calretinin expression was found compared with wild-type mice. These results indicate that Cacna1a mutation plays a significant role in protein expression patterns and that the tottering-6j mouse is a useful model for understanding protein expression mechanisms. PMID- 26887910 TI - Development of the anxiety scale for children with autism spectrum disorder (ASC ASD). AB - Many children with autism spectrum disorder (ASD) experience high levels of anxiety. A widely used measure for typically developing children is the Revised Child Anxiety and Depression Scale (RCADS). However, such anxiety measures may require adaptation to accommodate characteristics of those with ASD. An adapted version of the RCADS was created based on empirical evidence of anxiety phenomenology in ASD, which included additional items related to sensory anxiety, intolerance of uncertainty, and phobias. Content validity was refined during focus groups with parents. Polychoric factor analysis was undertaken on data from 170 children with ASD, aged 8-16, and their parents. This process resulted in the creation of a new 24 item scale (self and parent report) each with four subscales: Performance Anxiety, Uncertainty, Anxious Arousal, and Separation Anxiety, with evidence of good reliability and validity. The freely available Anxiety Scale for Children - ASD, Parent and Child versions (ASC-ASD) has promising psychometric properties including good internal consistency, validity, and 1 month test-retest reliability. Autism Res 2016, 9: 1205-1215. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26887909 TI - Enrichment of G2/M cell cycle phase in human pluripotent stem cells enhances HDR mediated gene repair with customizable endonucleases. AB - Efficient gene editing is essential to fully utilize human pluripotent stem cells (hPSCs) in regenerative medicine. Custom endonuclease-based gene targeting involves two mechanisms of DNA repair: homology directed repair (HDR) and non homologous end joining (NHEJ). HDR is the preferred mechanism for common applications such knock-in, knock-out or precise mutagenesis, but remains inefficient in hPSCs. Here, we demonstrate that synchronizing synchronizing hPSCs in G2/M with ABT phase increases on-target gene editing, defined as correct targeting cassette integration, 3 to 6 fold. We observed improved efficiency using ZFNs, TALENs, two CRISPR/Cas9, and CRISPR/Cas9 nickase to target five genes in three hPSC lines: three human embryonic stem cell lines, neural progenitors and diabetic iPSCs. neural progenitors and diabetic iPSCs. Reversible synchronization has no effect on pluripotency or differentiation. The increase in on-target gene editing is locus-independent and specific to the cell cycle phase as G2/M phase enriched cells show a 6-fold increase in targeting efficiency compared to cells in G1 phase. Concurrently inhibiting NHEJ with SCR7 does not increase HDR or improve gene targeting efficiency further, indicating that HR is the major DNA repair mechanism after G2/M phase arrest. The approach outlined here makes gene editing in hPSCs a more viable tool for disease modeling, regenerative medicine and cell-based therapies. PMID- 26887911 TI - A lack of credible evidence for a relationship between socio-economic status and dietary patterns: a response to 'Associations between socio-economic status and dietary patterns in US black and white adults'. PMID- 26887913 TI - Molecular dynamic simulations and structure-based pharmacophore development for farnesyltransferase inhibitors discovery. AB - Farnesyltransferase is one of the enzyme targets for the development of drugs for diseases, including cancer, malaria, progeria, etc. In the present study, the structure-based pharmacophore models have been developed from five complex structures (1LD7, 1NI1, 2IEJ, 2ZIR and 2ZIS) obtained from the protein data bank. Initially, molecular dynamic (MD) simulations were performed for the complexes for 10 ns using AMBER 12 software. The conformers of the complexes (75) generated from the equilibrated protein were undergone protein-ligand interaction fingerprint (PLIF) analysis. The results showed that some important residues, such as LeuB96, TrpB102, TrpB106, ArgB202, TyrB300, AspB359 and TyrB361, are predominantly present in most of the complexes for interactions. These residues form side chain acceptor and surface (hydrophobic or pi-pi) kind of interactions with the ligands present in the complexes. The structure-based pharmacophore models were generated from the fingerprint bits obtained from PLIF analysis. The pharmacophore models have 3-4 pharmacophore contours consist of acceptor and metal ligation (Acc & ML), hydrophobic (HydA) and extended acceptor (Acc2) features with the radius ranging between 1-3 A for Acc & ML and 1-2 A for HydA. The excluded volumes of the pharmacophore contours radius are between 1-2 A. Further, the distance between the interacting groups, root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radial distribution function (RDF) analysis were performed for the MD-simulated proteins using PTRAJ module. The generated pharmacophore models were used to screen a set of natural compounds and database compounds to select significant HITs. We conclude that the developed pharmacophore model can be a significant model for the identification of HITs as FTase inhibitors. PMID- 26887914 TI - Szidat's rule re-tested: relationships between flea and host phylogenetic clade ranks in four biogeographic realms. AB - We tested Szidat's rule (the more primitive the host, the more primitive the parasites it harbours) by analysing the relationships between phylogenetic clade ranks of fleas and their small mammalian hosts in four biogeographic realms (Afrotropics, Neotropics, Nearctic and Palearctic). From the host perspective, we tested the association between host clade rank and the mean clade rank of all fleas collected from this host. From the flea perspective, we tested the relationships between flea clade rank and the mean clade rank of hosts on which this flea was recorded. First, we tested whether the analysis of the relationships between host and flea clade ranks should be controlled for phylogenetic dependence among either host or flea species. Then, we tested for the associations between host and flea clade ranks separately for each realm using either a phylogenetic general least-squares analysis or an ordinary least squares analysis. In all realms, the mean clade rank of fleas parasitic on a given host increased with an increase of this host's clade rank, and the mean clade rank of hosts recorded on a given flea increased with an increase of this flea's clade rank, suggesting that Szidat's rule, at least to some extent, holds for fleas. PMID- 26887915 TI - Graduate nurses' experiences of mental health services in their first year of practice: An integrative review. AB - New graduate nurses have reported negative experiences in mental health settings, particularly during the transitional period of practice. Previous research has focused on addressing the undergraduate preparation of nurses for practice instead of the experiences and outcomes of the transitional period. Recently, there has been growing interest in exploring the experiences of graduate nurses in transition and the implementation of promising interventions to facilitate new graduates' assimilation to practice. Despite these initiatives, the overall shortage of mental health nurses continues to rise, and graduates still report negative experiences in the mental health setting. The purpose of this study was to identify and explore the experiences of new graduate nurses in mental health services in their first year of clinical practice. An integrative review was conducted with 22 studies sourced from the CINAHL, PubMed, Scopus, and PsychINFO electronic databases, as well as through hand-searching the literature. Literature review findings have highlighted negative clinical experiences and increased attrition from mental health services for graduate nurses. These experiences were closely linked with the changes in the training of mental health nurses, role ambiguity, inadequate clinical preceptorship, encountering the reality of mental health services, and the role of health services in transitioning graduate nurses into clinical practice. Established research into organizational cultures demonstrates that negative organizational outcomes result from negative workplace experiences. Therefore, further research into new graduate nurses' experiences of mental health nursing and its culture might clarify the reasons why they might not be attracted to the discipline and/or are leaving early in their career. PMID- 26887912 TI - Overlapping 16p13.11 deletion and gain of copies variations associated with childhood onset psychosis include genes with mechanistic implications for autism associated pathways: Two case reports. AB - Copy number variability at 16p13.11 has been associated with intellectual disability, autism, schizophrenia, epilepsy, and attention-deficit hyperactivity disorder. Adolescent/adult- onset psychosis has been reported in a subset of these cases. Here, we report on two children with CNVs in 16p13.11 that developed psychosis before the age of 7. The genotype and neuropsychiatric abnormalities of these patients highlight several overlapping genes that have possible mechanistic relevance to pathways previously implicated in Autism Spectrum Disorders, including the mTOR signaling and the ubiquitin-proteasome cascades. A careful screening of the 16p13.11 region is warranted in patients with childhood onset psychosis. PMID- 26887916 TI - Metonymy as Referential Dependency: Psycholinguistic and Neurolinguistic Arguments for a Unified Linguistic Treatment. AB - We examine metonymy at psycho- and neurolinguistic levels, seeking to adjudicate between two possible processing implementations (one- vs. two-mechanism). We compare highly conventionalized systematic metonymy (producer-for-product: "All freshmen read O'Connell") to lesser-conventionalized circumstantial metonymy ("[a waitress says to another:] 'Table 2 asked for more coffee."'). Whereas these two metonymy types differ in terms of contextual demands, they each reveal a similar dependency between the named and intended conceptual entities (e.g., Jackendoff, 1997; Nunberg, 1979, 1995). We reason that if each metonymy yields a distinct processing time course and substantially non-overlapping preferential localization pattern, it would not only support a two-mechanism view (one lexical, one pragmatic) but would suggest that conventionalization acts as a linguistic categorizer. By contrast, a similar behavior in time course and localization would support a one-mechanism view and the inference that conventionalization acts instead as a modulator of contextual felicitousness, and that differences in interpretation introduced by conventionalization are of degree, not of kind. Results from three paradigms: self-paced reading (SPR), event-related potentials (ERP), and functional magnetic resonance imaging (fMRI), reveal the following: no main effect by condition (metonymy vs. matched literal control) for either metonymy type immediately after the metonymy trigger, and a main effect for only the Circumstantial metonymy one word post-trigger (SPR); a N400 effect across metonymy types and a late positivity for Circumstantial metonymy (ERP); and a highly overlapping activation connecting the left ventrolateral prefrontal cortex and the left dorsolateral prefrontal cortex (fMRI). Altogether, the pattern observed does not reach the threshold required to justify a two-mechanism system. Instead, the pattern is more naturally (and conservatively) understood as resulting from the implementation of a generalized referential dependency mechanism, modulated by degree of context dependence/conventionalization, thus supporting architectures of language whereby "lexical" and "pragmatic" meaning relations are encoded along a cline of contextual underspecification. PMID- 26887917 TI - Putting Down Roots: How Nitrate and Abscisic Acid Help Shape Root System Architecture. PMID- 26887918 TI - The RNA Polymerase II C-Terminal Domain Phosphatase-Like Protein FIERY2/CPL1 Interacts with eIF4AIII and Is Essential for Nonsense-Mediated mRNA Decay in Arabidopsis. AB - Nonsense-mediated decay (NMD) is a posttranscriptional surveillance mechanism in eukaryotes that recognizes and degrades transcripts with premature translation termination codons. The RNA polymerase II C-terminal domain phosphatase-like protein FIERY2 (FRY2; also known as C-TERMINAL DOMAIN PHOSPHATASE-LIKE1 [CPL1]) plays multiple roles in RNA processing in Arabidopsis thaliana Here, we found that FRY2/CPL1 interacts with two NMD factors, eIF4AIII and UPF3, and is involved in the dephosphorylation of eIF4AIII. This dephosphorylation retains eIF4AIII in the nucleus and limits its accumulation in the cytoplasm. By analyzing RNA-seq data combined with quantitative RT-PCR validation, we found that a subset of alternatively spliced transcripts and 5'-extended mRNAs with NMD-eliciting features accumulated in the fry2-1 mutant, cycloheximide-treated wild type, and upf3 mutant plants, indicating that FRY2 is essential for the degradation of these NMD transcripts. PMID- 26887921 TI - Improving B3LYP heats of formation with three-dimensional molecular descriptors. AB - In the present work, we propose the X3D method that extends the B3LYP method by correcting its errors on heats of formation of hydrocarbons (HCs) with three dimensional (3D) molecular descriptors. Inspired by the widely used Wiener index, these 3D descriptors are developed to improve over the original B3LYP method for a better description of atom-atom, atom-bond and bond-bond interactions. On top of a training set of only 45 species, the X3D method is validated against various sets of different chemistry, displaying an overall near chemical accuracy. In particular, X3D improves over B3LYP, reducing its mean absolute errors from 28.4 to 0.3 kcal/mol for (Set 1) 21 n-alkanes up to n-C32 H66 , from 19.3 to 0.6 kcal/mol for (Set 2) n-C7 H16 and its branched isomers, from 29.5 to 1.6 kcal/mol for (Set 3) 36 polycyclic saturated HCs, from 8.6 to 1.1 kcal/mol for (Set 4) 41 C6 H8 isomers of rings, alkenes, alkynes, and cumulenes, from 20.3 to 0.6 kcal/mol for (Set 5) 41 benzene-based compounds, and 8.1 to 1.3 kcal/mol for (Set 6) 66 radicals, etc. Comparisons with the G4 results are also presented. (c) 2016 Wiley Periodicals, Inc. PMID- 26887919 TI - Environmental Nitrate Stimulates Abscisic Acid Accumulation in Arabidopsis Root Tips by Releasing It from Inactive Stores. AB - Abscisic acid (ABA) signaling plays a major role in root system development, regulating growth and root architecture. However, the precise localization of ABA remains undetermined. Here, we present a mechanism in which nitrate signaling stimulates the release of bioactive ABA from the inactive storage form, ABA glucose ester (ABA-GE). We found that ABA accumulated in the endodermis and quiescent center of Arabidopsis thaliana root tips, mimicking the pattern of SCARECROW expression, and (to lower levels) in the vascular cylinder. Nitrate treatment increased ABA levels in root tips; this stimulation requires the activity of the endoplasmic reticulum-localized, ABA-GE-deconjugating enzyme b GLUCOSIDASE1, but not de novo ABA biosynthesis. Immunogold labeling demonstrated that ABA is associated with cytoplasmic structures near, but not within, the endoplasmic reticulum. These findings demonstrate a mechanism for nitrate regulated root growth via regulation of ABA accumulation in the root tip, providing insight into the environmental regulation of root growth. PMID- 26887920 TI - No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor. AB - CONTEXT: Heparin-binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane (TM). OBJECTIVE: Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation. METHODS: A total of 12 mice had transtympanic injections of 5 MUg/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10 MUg/kg of HB-EGF. Intravenous blood samples were collected at 0-, 3-, 24-, 168-, 288- and 720-h post-injection. A double antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum. RESULTS: No mice in the transtympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls. DISCUSSION: The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant. CONCLUSIONS: HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect. PMID- 26887922 TI - Corrigendum: Delivery of crop pollination services is an insufficient argument for wild pollinator conservation. PMID- 26887923 TI - Photoluminescence and photocatalytic properties of rhombohedral CuGaO2 nanoplates. AB - Rhombohedral phase CuGaO2 nanoplates with a diameter of about 10 MUm were synthesized via low temperature hydrothermal method. Room temperature and low temperature photoluminescence of the obtained CuGaO2 nanoplates were characterized. CuGaO2 nanoplates exhibited blue emission at room temperature and free exciton emission were appeared at low temperature. The blue emission is originated from defects such as Cu vacancies, which is the possible origin of p type conductivity. The appearance of free exciton emission can demonstrate the direct bandgap transition behavior of CuGaO2 nanoplates. The as-prepared p-type CuGaO2 nanoplates were further decorated by n-type ZnO nanoparticles via calcination method to fabricate p-n junction nanocomposites. The nanocomposites exhibited enhanced photocatalytic activity which can be ascribed to the effective separation of photogenerated carriers by the internal electrostatic field in the p-n junction region, and the enhanced light absorption properties resulted from sub-bandgap absorption effect of p-n junction. This work has offered a new insight into the design of p-n junction devices using p-type CuGaO2 nanoplates. PMID- 26887925 TI - Esterase phenotyping in human liver in vitro: specificity of carboxylesterase inhibitors. AB - 1. Esterases may play a major role in the clearance of drugs with functional groups amenable to hydrolysis, particularly in the case of ester prodrugs. To understand the processes involved in the elimination of such drugs, it is necessary to determine the esterases involved. However, the tools currently available for this enzyme phenotyping are relatively scarce. 2. The work was aimed at summarizing the selectivity of esterase inhibitors for carboxylesterases 1 and 2 (CES1 and CES2) in the human liver to clarify their suitability for esterase phenotyping. Eserine, at around 10 MUM, was found to be a highly specific CES2 inhibitor, whereas other esterase inhibitors turned out less selective. When used together with tacrine, which inhibits cholinesterases but not CES, and ethylenediaminetetraacetic acid (inhibitor of paraoxonases), the involvement of the hydrolyzing esterases in the hepatic clearance of a drug can be elucidated. 3. The second approach to esterase phenotyping is based on data from recombinant or isolated esterases, together with relative activity factors, which relate their activities to those of the same enzymes in subcellular fractions. 4. These two approaches will help to characterize the hydrolytic metabolism of drug candidates in a similar manner as practiced routinely for the oxidative metabolism by cytochrome P450 enzymes. PMID- 26887926 TI - Inter- and Intra-Operator Reliability of Facial and Dental Measurements Using 3D Stereophotogrammetry. AB - OBJECTIVES: The goal of this study was to assess the reproducibility of an innovative method for facial analysis with three-dimensional-stereophotogrammetry (3D-spg). METHODS: Twelve subjects with no obvious malocclusion participated in this study. For each of them, four photographs were acquired using the LifeViz(TM) , an absolute calibration 3D-spg system. The facial reconstructions were analyzed with the DermaPix(TM) image management software. Two different operators recorded distances between landmarks and each operator repeated the measurements after one week. The intra- and inter-examiner reproducibilities were assessed using the Intraclass Correlation Coefficient (ICC). RESULTS: This study showed reproducible intra and inter-examiners results for facial measurements (ICC comprised between 0.732 and 0.976) except for measurements that involve the inner part of the dental corridor (ICC comprised between 0.598 and 0.914). CONCLUSION: The measurements recorded by 3D-LifeViz(TM) system are accurate and reliable for research and clinical use. Moreover, it is simple and inexpensive compared with other 3D methods (laser scanner, 3D Computed Tomography, and 3D Cone Beam CT). CLINICAL SIGNIFICANCE: The inter- and intra-operator reliability of the LifeViz(TM) 3D-spg method was demonstrated. The LifeViz(TM) 3D-spg method might be a useful method to accomplish indirect 3D measurements that are relevant to dental and facial diagnosis. (J Esthet Restor Dent, 2016). PMID- 26887927 TI - Pertrochanteric osteotomy and distraction femoral neck lengthening for treatment of proximal hip ischemic deformities in children. AB - PURPOSE: Proximal femoral ischemic deformities in the pediatric population is a challenging pathological situation. Many surgical techniques have been proposed to treat this problem, with variable reported results. We believe that a C-shaped pertrochanteric osteotomy plus neck lengthening utilizing distraction osteogenesis principles would restore the femoral anatomical ratios between neck, shaft, and the head, and redress the biomechanics of the proximal femur with resultant sufficient containment of the femoral head within the acetabulum. METHODS: We reviewed the results of 19 patients divided into two groups with proximal femoral ischemic deformities. Between 2002 and 2009, preoperative and postoperative clinical examination and radiographs were assessed measuring the neck-shaft angle (NSA), neck-epiphyseal angle (NEA), articulo-trochanteric distance (ATD), lateralization of the greater trochanter (LT), the angle of Wiberg (CEA), index of lateral head displacement by Reimers (IM), and lateral angle of displacement (LDA). RESULTS: All patients were followed prospectively. Clinical outcome was assessed using Colton's criteria, which showed average good improvement in function (58.9 %). Radiological indicators were assessed using Kruczynski's criteria. For group I, the postoperative NSA, NEA, and CEA showed significant change (p < 0.01, p < 0.001, and p < 0.001, respectively). For group II, the postoperative NSA, NEA, and CEA showed significant change (p < 0.001, p < 0.001, and p < 0.001, respectively). CONCLUSION: The midterm functional results are favorable for the implementation of pertrochanteric osteotomy and distraction osteogenesis to treat proximal femoral ischemic deformities in the pediatric population. PMID- 26887924 TI - Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration. AB - The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner. PMID- 26887928 TI - Increased isolation of nontuberculous mycobacteria among TB suspects in Northeastern, Tanzania: public health and diagnostic implications for control programmes. AB - BACKGROUND: Non-tuberculous mycobacteria (NTM) are increasingly reported worldwide associated with human disease. Defining the significance of NTM in settings with endemic tuberculosis (TB) requires the discrimination of NTM from TB in suspect patients. Correct and timely identification of NTM will impact both therapy and epidemiology of TB and TB-like diseases. The present study aimed at determining the frequency and diversity of NTM among TB suspects in northeastern Tanzania. METHODS: A cross-sectional study was conducted between November 2012 through January 2013. Seven hundred and forty-four sputum samples were collected from 372 TB suspects. Detection was done by using phenotypic, GenoType((r)) Mycobacterium CM/AS kits, 16S rRNA and hsp65 gene sequencing for identification of isolates not identified by Hain kits. Binary regression model was used to analyse the predictors of NTM detection. RESULTS: The prevalence of NTM was 9.7% of the mycobacterial isolates. Out of 36 patients with confirmed NTM infection, 12 were HIV infected with HIV being a significant predictor of NTM detection (P < 0.001). Co-infection with Mycobacterium tuberculosis (M. tb) was found in five patients. Twenty-eight NTM isolates were identified using GenoType((r)) Mycobacterium CM/AS and eight isolates could not be identified. Identified species included M. gordonae and M. interjectum 6 (16.7%), M. intracelullare 4 (11.1%), M. avium spp. and M. fortuitum 2 (5.5%), M. kansasii, M. lentiflavum, M. simiae, M. celatum, M. marinum 1 (2.8%) each. Of isolates not identified to subspecies level, we identified M. kumamotonense (2), M. intracellulare/kansasii, M. intermedium/triplex, M. acapulcensis/flavescens, M. stomatepiae, M. colombiense and M. terrae complex (1) each using 16S rRNA sequencing. Additionally, hsp65 gene sequencing identified M. kumamotonense, M. scrofulaceum/M. avium, M. avium, M. flavescens/novocastrense, M. kumamotonense/hiberniae, M. lentiflavum, M. colombiense/M. avium and M. kumamotonense/terrae/hiberniae (1) each. Results of the 16S rRNA and hsp65 gene sequencing were concordant in three and discordant in five isolates not identified by GenoType((r)) Mycobacterium CM/AS. CONCLUSION: NTM infections may play a vital role in causing lung disease and impact management of TB in endemic settings. GenoType((r)) Mycobacterium CM/AS represents a useful tool to identify clinical NTM infections. However, 16S rRNA gene sequencing should be thought for confirmatory diagnosis of the clinical isolates. Due to the complexity and inconsistence of NTM identification, we recommend diagnosis of NTM infections be centralized by strengthening and setting up quality national and regional infrastructure. PMID- 26887930 TI - Preparation of magnetic and pH-responsive chitosan microcapsules via sonochemical method. AB - Magnetic and pH-responsive chitosan microcapsules (MPRCMCs) were prepared by a simple sonochemical method. Superparamagnetic oleic acid modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) and hydrophobic drugs could be directly loaded into MPRCMCs during sonication. The obtained microcapsules had a well-defined spherical morphology with the average size of 2 MUm. The microcapsules showed an excellent magnetic property. In addition, the pH-responsive controlled release of coumarin 6 (C6) from MPRCMCs indicated that the developed microcapsules could be a promising candidate for drugs carriers. PMID- 26887929 TI - Amelioration of intracellular stress and reduction of neural tube defects in embryos of diabetic mice by phytochemical quercetin. AB - Diabetes mellitus in early pregnancy causes birth defects, including neural tube defects (NTDs). Hyperglycemia increases production of nitric oxide (NO) through NO synthase 2 (Nos2) and reactive oxygen species (ROS), generating nitrosative and oxidative stress conditions in the embryo. The present study aimed to target nitrosative stress using a naturally occurring Nos2 inhibitor, quercetin, to prevent NTDs in the embryos of diabetic mice. Daily administration of quercetin to diabetic pregnant mice during the hyperglycemia-susceptible period of organogenesis significantly reduced NTDs and cell apoptosis in the embryos, compared with those of vehicle-treated diabetic pregnant mice. Using HPLC-coupled ESI-MS/MS, quercetin metabolites, including methylated and sulfonylated derivatives, were detected in the conceptuses. The methylated metabolite, 3-O methylquercetin, was shown to reduce ROS level in embryonic stem cells cultured in high glucose. Quercetin treatment decreased the levels of Nos2 expression, protein nitrosylation, and protein nitration, alleviating nitrosative stress. Quercetin increased the expression of superoxide dismutase 1 and 2, and reduced the levels of oxidative stress markers. Expression of genes of redox regulating enzymes and DNA damage repair factors was upregulated. Our study demonstrates that quercetin ameliorates intracellular stresses, regulates gene expression, and reduces embryonic malformations in diabetic pregnancy. PMID- 26887932 TI - Corrigendum: Contractile dynamics change before morphological cues during fluorescence illumination. PMID- 26887931 TI - Symptoms suggestive of cow's milk allergy in infancy and pediatric inflammatory bowel disease. AB - BACKGROUND: Risk factors of pediatric inflammatory bowel disease (PIBD) are incompletely understood. Recently, we reported that among patients with PIBD, a previous diagnosis of cow's milk allergy (CMA) and asthma occurred more frequently than among age- and sex-matched peers. We tested at a national level the hypothesis that CMA is associated with the risk of contracting PIBD. METHODS: A nationwide birth cohort (n = 225,041), including all Finnish children born between 1999 and 2002, was followed up until July 1, 2014. We identified all children with a diagnosis of CMA, asthma, and PIBD from a national register; the data were based on certificates, including diagnostic criteria. The 95% confidence intervals (CI) for the incidence rates per 100,000 person-years were calculated assuming a Poisson distribution. RESULTS: We identified 7,910 infants with CMA yielding a cumulative incidence of 3.5% by 2 years of age. The cumulative incidence of PIBD was 0.14% (n = 316) and that of asthma 6.6% (14,807). Children with CMA were more likely to develop PIBD than non-CMA children, incidence ratio 2.6 (95% CI 1.7-3.8). Children with a diagnosis of CMA contracted PIBD at a younger age than the respective non-CMA group (9 vs. 11 years, p < 0.05). The risk was more evident for ulcerative colitis than for Crohn's disease. The association between CMA and asthma was stronger than that between CMA and PIBD. CONCLUSIONS: CMA in infancy is associated with subsequent development of asthma and PIBD. This suggests that in a subgroup of patients, CMA may share underlying background with PIBD, warranting thorough follow-up. PMID- 26887934 TI - On micro-electrokinetic scalar turbulence in microfluidics at a low Reynolds number. AB - We recently demonstrated the direct observation of micro-electrokinetic turbulence in a microchannel at a low Reynolds number (Re) when a pressure-driven flow was forced electrokinetically. Here, we characterize the corresponding scalar turbulence and surprisingly find that the corresponding turbulent mixing has some typical and important features of scalar turbulence, such as the Obukhov Corrsin (O-C) -5/3 spectrum of concentration fluctuation, which can commonly be realized only at high Re in macroflows. This discovery could provide a new perspective of scalar turbulence and an avenue for control of transport phenomena in lab-on-a-chip platforms. This will deepen our fundamental understanding of transport phenomena in microfluidics. PMID- 26887933 TI - Vaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy. AB - Previously, we combined p19(Arf) (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-beta, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19(Arf) and IFN-beta are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19(Arf) and IFN-beta treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4(+) and CD8(+) T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN beta alone or combined with p19(Arf) conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19(Arf) and IFN-beta combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma. PMID- 26887936 TI - Author's reply to Goldacre. PMID- 26887935 TI - Plasmodium vivax mdr1 genotypes in isolates from successfully cured patients living in endemic and non-endemic Brazilian areas. AB - BACKGROUND: Plasmodium vivax is the most widely distributed species causing the highest number of malaria cases in the world. In Brazil, P. vivax is responsible for approximately 84 % of reported cases. In the absence of a vaccine, control strategies are based on the management of cases through rapid diagnosis and adequate treatment, in addition to vector control measures. The approaches used to investigate P. vivax resistance to chloroquine (CQ) were exclusively in vivo studies because of the difficulty in keeping parasites in continuous in vitro culture. In view of the limitations related to follow-up of patients and to assessing the plasma dosage of CQ and its metabolites, an alternative approach to monitor chemo-resistance (QR) is to use molecular markers. Single nucleotide polymorphisms (SNPs) in the multidrug resistance gene pvmdr1 are putative determinants of CQ resistance (CQR), but such SNPs in P. vivax isolates from patients with good response to treatment should be further explored. The aim of this study is to investigate the mutations in the gene, supposedly associated to QR, in P. vivax isolates from successfully cured patients, living in Brazilian endemic and non-endemic areas. METHODS: Blood samples were collected from 49 vivax malaria patients from endemic (Amazon Basin: 45) and non-endemic (Atlantic Forest: four) Brazilian regions and analysed for SNPs in the CQR-related P. vivax gene (pvmdr1), using PCR-based methods. RESULTS: Among the 49 isolates genetically characterized for the gene pvmdr1, 34 (70 %) presented at least one mutation. T958M mutant alleles were the most frequent (73 %) followed Y976F (15 %) and F1076L (12 %). Single mutation was detected in 24 (70.5 %) isolates and double mutations in ten (29.5 %). The most common single mutant genotype was the 958M/Y976/F1076 (79 %), followed by 976F/F1076 (21 %) whereas 958M/Y976/1076L (60 %) and 976F/1076L (40 %) double mutant genotypes were detected. Single mutant profile was observed only in isolates from Amazon Basin, although double mutants were found both in the Amazon and Atlantic Forest regions. Interestingly, the genotype 958M/Y976/1076L was present in all isolates from the Atlantic Forest in the Rio de Janeiro State. CONCLUSIONS: Considering that primaquine (PQ) efficacy is highly dependent on concurrent administration of a blood schizontocidal agent and that PQ could not circumvent CQR, together with the fact that no pvmdr1 mutation should be expected in successfully cured patients, these findings seem to indicate that the pvmdr1 gene is not a reliable marker of CQR. Further investigations are needed to define a reliable molecular marker for monitoring P. vivax CQR in P. vivax populations. PMID- 26887937 TI - Achieving Precision Mental Health through Effective Assessment, Monitoring, and Feedback Processes : Introduction to the Special Issue. PMID- 26887938 TI - GIV/Girdin (Galpha-interacting, Vesicle-associated Protein/Girdin) Creates a Positive Feedback Loop That Potentiates Outside-in Integrin Signaling in Cancer Cells. AB - Activation of the tyrosine kinase focal adhesion kinase (FAK) upon cell stimulation by the extracellular matrix initiates integrin outside-in signaling. FAK is directly recruited to active integrins, which enhances its kinase activity and triggers downstream signaling like activation of PI3K. We recently described that Galpha-interacting, vesicle-associated protein (GIV), a protein up-regulated in metastatic cancers, is also required for outside-in integrin signaling. More specifically, we found that GIV is a non-receptor guanine nucleotide exchange factor that activates trimeric G proteins in response to integrin stimulation to enhance PI3K signaling and tumor cell migration. In contrast, previous reports have established that GIV is involved in phosphotyrosine (Tyr(P))-based signaling in response to growth factor stimulation;i.e.GIV phosphorylation at Tyr-1764 and Tyr-1798 recruits and activates PI3K. Here we show that phosphorylation of GIV at Tyr-1764/Tyr-1798 is also required to enhance PI3K-Akt signaling and tumor cell migration in response to integrin stimulation, indicating that GIV functions in Tyr(P)-dependent integrin signaling. Unexpectedly, we found that activation of FAK, an upstream component of the integrin Tyr(P) signaling cascade, was diminished in GIV-depleted cells, suggesting that GIV is required to establish a positive feedback loop that enhances integrin-FAK signaling. Mechanistically, we demonstrate that this feedback activation of FAK depends on both guanine nucleotide exchange factor and Tyr(P) GIV signaling as well as on their convergence point, PI3K. Taken together, our results provide novel mechanistic insights into how GIV promotes proinvasive cancer cell behavior by working as a signal-amplifying platform at the crossroads of trimeric G protein and Tyr(P) signaling. PMID- 26887939 TI - Protein Kinase C zeta Interacts with a Novel Binding Region of Galphaq to Act as a Functional Effector. AB - Heterotrimeric G proteins play an essential role in the initiation of G protein coupled receptor (GPCR) signaling through specific interactions with a variety of cellular effectors. We have recently reported that GPCR activation promotes a direct interaction between Galphaq and protein kinase C zeta (PKCzeta), leading to the stimulation of the ERK5 pathway independent of the canonical effector PLCbeta. We report herein that the activation-dependent Galphaq/PKCzeta complex involves the basic PB1-type II domain of PKCzeta and a novel interaction module in Galphaq different from the classical effector-binding site. Point mutations in this Galphaq region completely abrogate ERK5 phosphorylation, indicating that Galphaq/PKCzeta association is required for the activation of the pathway. Indeed, PKCzeta was demonstrated to directly bind ERK5 thus acting as a scaffold between Galphaq and ERK5 upon GPCR activation. The inhibition of these protein complexes by G protein-coupled receptor kinase 2, a known Galphaq modulator, led to a complete abrogation of ERK5 stimulation. Finally, we reveal that Galphaq/PKCzeta complexes link Galphaq to apoptotic cell death pathways. Our data suggest that the interaction between this novel region in Galphaq and the effector PKCzeta is a key event in Galphaq signaling. PMID- 26887940 TI - Multiple Mechanisms Contribute to the Cell Growth Defects Imparted by Human Telomerase Insertion in Fingers Domain Mutations Associated with Premature Aging Diseases. AB - Normal human stem cells rely on low levels of active telomerase to sustain their high replicative requirements. Deficiency in telomere maintenance mechanisms leads to the development of premature aging diseases, such as dyskeratosis congenita and aplastic anemia. Mutations in the unique "insertion in fingers domain" (IFD) in the human telomerase reverse transcriptase catalytic subunit (hTERT) have previously been identified and shown to be associated with dyskeratosis congenita and aplastic anemia. However, little is known about the molecular mechanisms impacted by these IFD mutations. We performed comparative functional analyses of disease-associated IFD variants at the molecular and cellular levels. We report that hTERT-P721R- and hTERT-R811C-expressing cells exhibited growth defects likely due to impaired TPP1-mediated recruitment of these variant enzymes to telomeres. We showed that activity and processivity of hTERT-T726M failed to be stimulated by TPP1-POT1 overexpression and that dGTP usage by this variant was less efficient compared with the wild-type enzyme. hTERT-P785L-expressing cells did not show growth defects, and this variant likely confers cell survival through increased DNA synthesis and robust activity stimulation by TPP1-POT1. Altogether, our data suggest that multiple mechanisms contribute to cell growth defects conferred by the IFD variants. PMID- 26887941 TI - Evidence That the "Lid" Domain of Nicastrin Is Not Essential for Regulating gamma Secretase Activity. AB - Understanding of the structure of the gamma-secretase complex consisting of presenilin (PS), anterior pharynx-defective 1 (APH-1), nicastrin (NCT), and presenilin enhancer 2 (PEN-2) is of significant therapeutic interest for the design of gamma-secretase modulators for Alzheimer disease. The structure of gamma-secretase revealed by cryo-EM approaches suggested a substrate binding mechanism for NCT, a bilobar structure that involved rotation of the two lobes around a central pivot and opening of a "lid" region that facilitates substrate recruitment. To validate this proposal, we expressed NCT that lacks the lid entirely, or a variety of NCT variants that harbor mutations at highly conserved residues in the lid region inNCT-deficient cells, and then assessed their impact on gamma-secretase assembly, activity, and stability. In addition, we assessed the impact of mutating a critical residue proposed to be a pivot around which the two lobes of NCT rotate. Our results show that neither the mutations on the lid tested here nor the entire lid deletion has any significant impact on gamma secretase assembly, activity, and stability, and that NCT with the mutation of the proposed pivot rescues gamma-secretase activity inNCT-deficient cells in a manner indistinguishable from WT NCT. These findings indicate that the NCT lid is not an essential element necessary for gamma-secretase assembly, activity, and stability, and that rotation of the two lobes appears not to be a prerequisite for substrate binding and gamma-secretase function. PMID- 26887943 TI - Differentiated, Promoter-specific Response of [4Fe-4S] NsrR DNA Binding to Reaction with Nitric Oxide. AB - NsrR is an iron-sulfur cluster protein that regulates the nitric oxide (NO) stress response of many bacteria. NsrR from Streptomyces coelicolor regulates its own expression and that of only two other genes, hmpA1 and hmpA2, which encode HmpA enzymes predicted to detoxify NO. NsrR binds promoter DNA with high affinity only when coordinating a [4Fe-4S] cluster. Here we show that reaction of [4Fe-4S] NsrR with NO affects DNA binding differently depending on the gene promoter. Binding to the hmpA2 promoter was abolished at ~2 NO per cluster, although for the hmpA1 and nsrR promoters, ~4 and ~8 NO molecules, respectively, were required to abolish DNA binding. Spectroscopic and kinetic studies of the NO reaction revealed a rapid, multi-phase, non-concerted process involving up to 8-10 NO molecules per cluster, leading to the formation of several iron-nitrosyl species. A distinct intermediate was observed at ~2 NO per cluster, along with two further intermediates at ~4 and ~6 NO. The NsrR nitrosylation reaction was not significantly affected by DNA binding. These results show that NsrR regulates different promoters in response to different concentrations of NO. Spectroscopic evidence indicates that this is achieved by different NO-FeS complexes. PMID- 26887942 TI - Path to Collagenolysis: COLLAGEN V TRIPLE-HELIX MODEL BOUND PRODUCTIVELY AND IN ENCOUNTERS BY MATRIX METALLOPROTEINASE-12. AB - Collagenolysis is essential in extracellular matrix homeostasis, but its structural basis has long been shrouded in mystery. We have developed a novel docking strategy guided by paramagnetic NMR that positions a triple-helical collagen V mimic (synthesized with nitroxide spin labels) in the active site of the catalytic domain of matrix metalloproteinase-12 (MMP-12 or macrophage metalloelastase) primed for catalysis. The collagenolytically productive complex forms by utilizing seven distinct subsites that traverse the entire length of the active site. These subsites bury ~1,080 A(2)of surface area, over half of which is contributed by the trailing strand of the synthetic collagen V mimic, which also appears to ligate the catalytic zinc through the glycine carbonyl oxygen of its scissile G~VV triplet. Notably, the middle strand also occupies the full length of the active site where it contributes extensive interfacial contacts with five subsites. This work identifies, for the first time, the productive and specific interactions of a collagen triple helix with an MMP catalytic site. The results uniquely demonstrate that the active site of the MMPs is wide enough to accommodate two strands from collagen triple helices. Paramagnetic relaxation enhancements also reveal an extensive array of encounter complexes that form over a large part of the catalytic domain. These transient complexes could possibly facilitate the formation of collagenolytically active complexes via directional Brownian tumbling. PMID- 26887944 TI - Redox Control of the Human Iron-Sulfur Repair Protein MitoNEET Activity via Its Iron-Sulfur Cluster. AB - Human mitoNEET (mNT) is the first identified Fe-S protein of the mammalian outer mitochondrial membrane. Recently, mNT has been implicated in cytosolic Fe-S repair of a key regulator of cellular iron homeostasis. Here, we aimed to decipher the mechanism by which mNT triggers its Fe-S repair capacity. By using tightly controlled reactions combined with complementary spectroscopic approaches, we have determined the differential roles played by both the redox state of the mNT cluster and dioxygen in cluster transfer and protein stability. We unambiguously demonstrated that only the oxidized state of the mNT cluster triggers cluster transfer to a generic acceptor protein and that dioxygen is neither required for the cluster transfer reaction nor does it affect the transfer rate. In the absence of apo-acceptors, a large fraction of the oxidized holo-mNT form is converted back to reduced holo-mNT under low oxygen tension. Reduced holo-mNT, which holds a [2Fe-2S](+)with a global protein fold similar to that of the oxidized form is, by contrast, resistant in losing its cluster or in transferring it. Our findings thus demonstrate that mNT uses an iron-based redox switch mechanism to regulate the transfer of its cluster. The oxidized state is the "active state," which reacts promptly to initiate Fe-S transfer independently of dioxygen, whereas the reduced state is a "dormant form." Finally, we propose that the redox-sensing function of mNT is a key component of the cellular adaptive response to help stress-sensitive Fe-S proteins recover from oxidative injury. PMID- 26887945 TI - IL23R (Interleukin 23 Receptor) Variants Protective against Inflammatory Bowel Diseases (IBD) Display Loss of Function due to Impaired Protein Stability and Intracellular Trafficking. AB - Genome-wide association studies as well as murine models have shown that the interleukin 23 receptor (IL23R) pathway plays a pivotal role in chronic inflammatory diseases such as Crohn disease (CD), ulcerative colitis, psoriasis, and type 1 diabetes. Genome-wide association studies and targeted re-sequencing studies have revealed the presence of multiple potentially causal variants of the IL23R. Specifically the G149R, V362I, and R381Q IL23Ralpha chain variants are linked to protection against the development of Crohn disease and ulcerative colitis in humans. Moreover, the exact mechanism of action of these receptor variants has not been elucidated. We show that all three of these IL23Ralpha variants cause a reduction in IL23 receptor activation-mediated phosphorylation of the signal-transducing activator of transcription 3 (STAT3) and phosphorylation of signal transducing activator of transcription 4 (STAT4). The reduction in signaling is due to lower levels of cell surface receptor expression. For G149R, the receptor retention in the endoplasmic reticulum is due to an impairment of receptor maturation, whereas the R381Q and V362I variants have reduced protein stability. Finally, we demonstrate that the endogenous expression of IL23Ralpha protein from V362I and R381Q variants in human lymphoblastoid cell lines exhibited lower expression levels relative to susceptibility alleles. Our results suggest a convergent cause of IL23Ralpha variant protection against chronic inflammatory disease. PMID- 26887948 TI - The Pleckstrin Homology Domain of Diacylglycerol Kinase eta Strongly and Selectively Binds to Phosphatidylinositol 4,5-Bisphosphate. AB - Type II diacylglycerol kinase (DGK) isozymes (delta, eta, and kappa) have a pleckstrin homology domain (PH) at their N termini. Here, we investigated the lipid binding properties of the PHs of type II DGK isozymes using protein-lipid overlay and liposome binding assays. The PH of DGKeta showed the most pronounced binding activity to phosphatidylinositol (PI) 4,5-bisphosphate (PI(4,5)P2) among the various glycero- and sphingolipids including PI 3,4,5-trisphosphate, PI 3,4 bisphosphate, PI 3-phosphate, PI 4-phosphate, and PI 5-phosphate. Moreover, the PI(4,5)P2binding activity of the DGKeta-PH was significantly stronger than that of other type II DGK isozymes. Notably, compared with the PH of phospholipase C (PLC) delta1, which is generally utilized as a cellular PI(4,5)P2- probe, the DGKeta-PH is equal to or superior than the PLCdelta1-PH in terms of affinity and selectivity for PI(4,5)P2 Furthermore, in COS-7 cells, GFP-fused wild-type DGKeta1 and its PH partly translocated from the cytoplasm to the plasma membrane where the PLCdelta1-PH was co-localized in response to hyperosmotic stress in an inositol 5-phosphatase-sensitive manner, whereas a PH deletion mutant did not. Moreover, K74A and R85A mutants of DGKeta-PH, which lack the conserved basic amino acids thought to ligate PI(4,5)P2, were indeed unable to bind to PI(4,5)P2and co-localize with the PLCdelta1-PH even in osmotically shocked cells. Overexpression of wild-type DGKeta1 enhanced EGF-dependent phosphorylation of ERK, whereas either K74A or R85A mutant did not. Taken together, these results indicate that the DGKeta-PH preferentially interacts with PI(4,5)P2and has crucial roles in regulating the subcellular localization and physiological function of DGKeta. Moreover, the DGKeta-PH could serve as an excellent cellular sensor for PI(4,5)P2. PMID- 26887946 TI - Fungal Chitin Induces Trained Immunity in Human Monocytes during Cross-talk of the Host with Saccharomyces cerevisiae. AB - The immune system is essential to maintain the mutualistic homeostatic interaction between the host and its micro- and mycobiota. Living as a commensal,Saccharomyces cerevisiaecould potentially shape the immune response in a significant way. We observed thatS. cerevisiaecells induce trained immunity in monocytes in a strain-dependent manner through enhanced TNFalpha and IL-6 production upon secondary stimulation with TLR ligands, as well as bacterial and fungal commensals. Differential chitin content accounts for the differences in training properties observed among strains, driving induction of trained immunity by increasing cytokine production and direct antimicrobial activity bothin vitroandin vivo These chitin-induced protective properties are intimately associated with its internalization, identifying a critical role of phagosome acidification to facilitate microbial digestion. This study reveals how commensal and passenger microorganisms could be important in promoting health and preventing mucosal diseases by modulating host defense toward pathogens and thus influencing the host microbiota-immune system interactions. PMID- 26887947 TI - Templated Aggregation of TAR DNA-binding Protein of 43 kDa (TDP-43) by Seeding with TDP-43 Peptide Fibrils. AB - TAR DNA-binding protein of 43 kDa (TDP-43) has been identified as the major component of ubiquitin-positive neuronal and glial inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Aggregation of TDP-43 to amyloid-like fibrils and spreading of the aggregates are suggested to account for the pathogenesis and progression of these diseases. To investigate the molecular mechanisms of TDP-43 aggregation, we attempted to identify the amino acid sequence required for the aggregation. By expressing a series of deletion mutants lacking 20 amino acid residues in the C-terminal region in SH-SY5Y cells, we established that residues 274-313 in the glycine-rich region are essential for aggregation. In vitro aggregation experiments using synthetic peptides of 40 amino acids from this sequence and adjacent regions showed that peptides 274-313 and 314-353 formed amyloid-like fibrils. Transduction of these fibrils induced seed-dependent aggregation of TDP-43 in cells expressing wild-type TDP-43 or TDP 43 lacking nuclear localization signal. These cells showed different phosphorylated C-terminal fragments of TDP-43 and different trypsin-resistant bands. These results suggest that residues 274-353 are responsible for the conversion of TDP-43 to amyloid-like fibrils and that templated aggregation of TDP-43 by seeding with different peptides induces various types of TDP-43 pathologies, i.e. the peptides appear to act like prion strains. PMID- 26887949 TI - GSK3beta Overexpression in Dentate Gyrus Neural Precursor Cells Expands the Progenitor Pool and Enhances Memory Skills. AB - In restricted areas of the adult brain, like the subgranular zone of the dentate gyrus (DG), there is continuous production of new neurons. This process, named adult neurogenesis, is involved in important cognitive functions such as memory and learning. It requires the presence of newborn neurons that arise from neuronal stem cells, which divide and differentiate through successive stages in adulthood. In this work, we demonstrate that overexpression of glycogen synthase kinase (GSK) 3beta in neural precursor cells (NPCs) using the glial fibrillary acidic protein promoter during DG development produces an increase in the neurogenic process, increasing NPCs numbers. Moreover, the transgenic mice show higher DG volume and increased number of mature granule neurons. In an attempt to compensate for these alterations, glial fibrillary acidic protein/GSK3beta overexpressing mice show increased levels of Dkk1 and sFRP3, two inhibitors of the Wnt-frizzled complex. We have also found behavioral differences between wild type and transgenic mice, indicating a higher rating in memory tasks for GSK3beta overexpressing mice compared with wild type mice. These data indicate that GSK3beta is a crucial kinase in NPC physiology and suggest that this molecule plays a key role in the correct development of DG and adult neurogenesis in this region. PMID- 26887950 TI - Importin alpha1 Mediates Yorkie Nuclear Import via an N-terminal Non-canonical Nuclear Localization Signal. AB - The Hippo signaling pathway controls organ size by orchestrating cell proliferation and apoptosis. When the Hippo pathway was inactivated, the transcriptional co-activator Yorkie translocates into the nucleus and forms a complex with transcription factor Scalloped to promote the expression of Hippo pathway target genes. Therefore, the nuclear translocation of Yorkie is a critical step in Hippo signaling. Here, we provide evidence that the N-terminal 1 55 amino acids of Yorkie, especially Arg-15, were essential for its nuclear localization. By mass spectrometry and biochemical analyses, we found that Importin alpha1 can directly interact with the Yorkie N terminus and drive Yorkie into the nucleus. Further experiments show that the upstream component Hippo can inhibit Importin alpha1-mediated Yorkie nuclear import. Taken together, we identified a potential nuclear localization signal at the N-terminal end of Yorkie as well as a critical role for Importin alpha1 in Yorkie nuclear import. PMID- 26887951 TI - A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement. AB - Eukaryotic mRNA biogenesis involves a series of interconnected steps mediated by RNA-binding proteins. The exon junction complex core protein Y14 is required for nonsense-mediated mRNA decay (NMD) and promotes translation. Moreover, Y14 binds the cap structure of mRNAs and inhibits the activity of the decapping enzyme Dcp2. In this report, we show that an evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for its binding to the mRNA cap structure. A Trp-73 mutant (W73V) bound weakly to mRNAs and failed to protect them from degradation. However, this mutant could still interact with the NMD and mRNA degradation factors and retained partial NMD activity. In addition, we found that the W73V mutant could not interact with translation initiation factors. Overexpression of W73V suppressed reporter mRNA translation in vitro and in vivo and reduced the level of a set of nascent proteins. These results reveal a residue of Y14 that confers cap-binding activity and is essential for Y14-mediated enhancement of translation. Finally, we demonstrated that Y14 may selectively and differentially modulate protein biosynthesis. PMID- 26887952 TI - Enzyme Activities of the Ceramide Synthases CERS2-6 Are Regulated by Phosphorylation in the C-terminal Region. AB - Ceramide and complex sphingolipids regulate important cellular functions including cell growth, apoptosis, and signaling. Dysregulation of sphingolipid metabolism leads to pathological consequences such as sphingolipidoses and insulin resistance. Ceramides in mammals vary greatly in their acyl-chain composition: six different ceramide synthase isozymes (CERS1-6) that exhibit distinct substrate specificity and tissue distribution account for this diversity. In the present study, we demonstrated that CERS2-6 were phosphorylated at the cytoplasmic C-terminal regions. Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. Phosphorylation modestly increased the catalytic activities of CERS4 and -5 and mildly increased those of CERS3 and -6. Dephosphorylation of endogenous ceramide synthases in the mouse brain led to severely reduced activity toward the Cers2 substrates C22:0/C24:0-CoAs and modestly reduced activity toward the Cers5/6 substrate C16:0-CoA. These results suggest that the phosphorylation of ceramide synthases may be a key regulatory point in the control of the distribution and levels of sphingolipids of various acyl-chain lengths. PMID- 26887953 TI - Cholesterol-mediated Degradation of 7-Dehydrocholesterol Reductase Switches the Balance from Cholesterol to Vitamin D Synthesis. AB - Cholesterol is detrimental to human health in excess but is also essential for normal embryogenesis. Hence, enzymes involved in its synthesis possess many layers of regulation to achieve balanced cholesterol levels. 7-Dehydrocholesterol reductase (DHCR7) is the terminal enzyme of cholesterol synthesis in the Kandutsch-Russell pathway, converting 7-dehydrocholesterol (7DHC) to cholesterol. In the absence of functional DHCR7, accumulation of 7DHC and a lack of cholesterol production leads to the devastating developmental disorder, Smith Lemli-Opitz syndrome. This study identifies that statin treatment can ameliorate the low DHCR7 expression seen with common Smith-Lemli-Opitz syndrome mutations. Furthermore, we show that wild-type DHCR7 is also relatively labile. In an example of end-product inhibition, cholesterol accelerates the proteasomal degradation of DHCR7, resulting in decreased protein levels and activity. The loss of enzymatic activity results in the accumulation of the substrate 7DHC, which leads to an increased production of vitamin D. Thus, these findings highlight DHCR7 as an important regulatory switch between cholesterol and vitamin D synthesis. PMID- 26887955 TI - Translation, validity and reliability of the British Sign Language (BSL) version of the EQ-5D-5L. AB - PURPOSE: To translate the health questionnaire EuroQol EQ-5D-5L into British Sign Language (BSL), to test its reliability with the signing Deaf population of BSL users in the UK and to validate its psychometric properties. METHODS: The EQ-5D 5L BSL was developed following the international standard for translation required by EuroQol, with additional agreed features appropriate to a visual language. Data collection used an online platform to view the signed (BSL) version of the tests. The psychometric testing included content validity, assessed by interviewing a small sample of Deaf people. Reliability was tested by internal consistency of the items and test-retest, and convergent validity was assessed by determining how well EQ-5D-5L BSL correlates with CORE-10 BSL and CORE-6D BSL. RESULTS: The psychometric properties of the EQ-5D-5L BSL are good, indicating that it can be used to measure health status in the Deaf signing population in the UK. Convergent validity between EQ-5D-5L BSL and CORE-10 BSL and CORE-6D BSL is consistent, demonstrating that the BSL version of EQ-5D-5L is a good measure of the health status of an individual. The test-retest reliability of EQ-5D-5L BSL, for each dimension of health, was shown to have Cohen's kappa values of 0.47-0.61; these were in the range of moderate to good and were therefore acceptable. CONCLUSIONS: This is the first time EQ-5D-5L has been translated into a signed language for use with Deaf people and is a significant step forward towards conducting studies of health status and cost-effectiveness in this population. PMID- 26887954 TI - Extracellular RNAs: A Secret Arm of Immune System Regulation. AB - The immune system has evolved to protect multicellular organisms from the attack of a variety of pathogens. To exert this function efficiently, the system has developed the capacity to coordinate the function of different cell types and the ability to down-modulate the response when the foreign attack is over. For decades, immunologists believed that these two characteristics were primarily related to cytokine/chemokine-based communication and cell-to-cell direct contact. More recently, it has been shown that immune cells also communicate by transferring regulatory RNAs, microRNAs in particular, from one cell to the other. Several studies have suggested a functional role of extracellular regulatory RNAs in cell-to-cell communication in different cellular contexts. This minireview focuses on the potential role of extracellular RNA transfer in the regulation of adaptive immune response, also contextualizing it in a broader field of what is known of cell-free RNAs in communication among different organisms in the evolutionary scale. PMID- 26887956 TI - Phase II study on the efficacy and safety of Lapatinib administered beyond disease progression and combined with vinorelbine in HER-2/neu- positive advanced breast cancer: results of the CECOG LaVie trial. AB - BACKGROUND: Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when combined with lapatinib, an anti-HER2 tyrosine-kinase inhibitor, as late-line regimen administered beyond previous disease progression on prior lapatinib in patients with HER-2/neu- positive MBC. METHODS: The CECOG LaVie study was designed as open-labeled, single-arm, multicenter phase II trial. Patients had to be pretreated with lapatinib plus chemotherapy, and received lapatinib at a daily dose of 1250 mg in combination with vinorelbine 20 mg/m(2) i.v. on days 1 and 8 of a three-week cycle until disease progression, intolerable toxicity or withdrawal of consent. Progression-free survival (PFS) was defined as primary study endpoint; secondary endpoints included overall survival (OS), response rate according to RECIST 1.1, and safety. The study was terminated early due to poor accrual. RESULTS: A total number of nine patients were included; lapatinib administered beyond disease progression combined with vinorelbine resulted in a median PFS of 7.7 months (95% CI 0.56-14.91) and a median OS of 23.4 months (95% CI 16.61-30.13), respectively. Partial remission was seen in one of nine patients, three patients had stable disease of > six months, whereas the remaining five patients had primary disease progression. In two patients, modification of vinorelbine dose due to toxicity became necessary; no dose modification was needed for lapatinib. The majority of reported adverse events (AE) were grade 1 and 2 in severity with diarrhea being the most commonly observed AE CONCLUSION: In this heavily pretreated patient population, combination of vinorelbine plus lapatinib showed encouraging activity and was characterized by an acceptable safety profile. Despite the low patient number, lapatinib plus vinorelbine may constitute a potential treatment option in heavily pretreated patients with HER-2/neu-positive MBC previously exposed to lapatinib. TRIAL REGISTRATION: EudraCT number 2009-016826-15, (15. 10.2009). PMID- 26887957 TI - Liver X receptor alpha is essential for the capillarization of liver sinusoidal endothelial cells in liver injury. AB - Liver X receptors (LXRs) play essential roles in lipogenesis, anti-inflammatory action and hepatic stellate cells (HSCs) activation in the liver. However, the effects of LXRs on the capillarization of liver sinusoidal endothelial cells (LSECs) in liver fibrosis remain undetermined. Here, we demonstrated that LXRalpha plays an important role in LSECs capillarization in a manner that involved Hedgehog (Hh) signaling. We found that LXRalpha expression in LSECs was increased in the carbon tetrachloride (CCl4)-induced fibrosis model. LXRalpha deletion markedly exacerbated CCl4-induced lesions assessed by histopathology, as well as inflammation and collagen deposition. Furthermore, capillarization of the sinusoids was aggravated in CCl4 -treated LXRalpha-deficient mice, as evidenced by increased CD34 expression, the formation of continuous basement membranes and aggravation of the loss of fenestrae. In vitro, LXR agonist could maintain freshly isolated LSECs differentiation on day 3. Furthermore, LXRalpha deletion led to increased expression of Hedgehog (Hh)-regulated gene in LSECs in the injured liver. Conversely, the LXR agonist could inhibit the Hh pathway in cultured LSECs. These responses indicated that LXRalpha suppressed the process of LSECs capillarization by repressing Hh signaling. Overall, our findings suggest that LXRalpha, by restoring the differentiation of LSECs, may be critical for the regression of liver fibrosis. PMID- 26887960 TI - Treatment no-show in forensic outpatients with ADHD. AB - BACKGROUND: 'No-show' is important in today's mental healthcare services, yet in forensic psychiatry, little is known about its relationship to general and disorder-specific patient characteristics. AIMS: The aim of this article is to determine the prevalence of no-show and any general and disorder-specific features associated with no-show in a cohort of offenders with attention deficit hyperactivity disorder registered at a specialist forensic mental health clinic. METHODS: Participants were 118 adult men with a mean age just over 32 years (SD 8.75) attending forensic mental health outpatient clinics in the Netherlands who had a primary diagnosis of attention deficit hyperactivity disorder and who had been aggressive and/or delinquent. RESULTS: Over a 1-year period, most patients (101, 86%) missed at least one appointment. The average number of appointments offered was 37.88 (SD = 27.27), and the average number of no-shows was 6.53 (SD = 5.99) per patient. Multivariate linear regressions showed a 10-fold likelihood of later no-shows if the first appointment was missed; not showing up after the intake procedure was also associated with higher rates of later no-show. None of the disorder-specific characteristics contributed to the problem. CONCLUSIONS: No show is of particular concern in forensic mental health settings. In the current study, no-show was primarily associated with features related to the time of initial consultation. More attention should thus be paid at this stage to using a standard method of assessing a wider range of variables likely to affect attendance. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887959 TI - Association Between Media Dose, Ad Tagging, and Changes in Web Traffic for a National Tobacco Education Campaign: A Market-Level Longitudinal Study. AB - BACKGROUND: In 2012, the US Centers for Disease Control and Prevention (CDC) launched Tips From Former Smokers (Tips), the first federally funded national tobacco education campaign. In 2013, a follow-up Tips campaign aired on national cable television networks, radio, and other channels, with supporting digital advertising to drive traffic to the Tips campaign website. OBJECTIVE: The objective of this study was to use geographic and temporal variability in 2013 Tips campaign television media doses and ad tagging to evaluate changes in traffic to the campaign website in response to specific doses of campaign media. METHODS: Linear regression models were used to estimate the dose-response relationship between weekly market-level television gross rating points (GRPs) and weekly Web traffic to the Tips campaign website. This relationship was measured using unique visitors, total visits, and page views as outcomes. Ad GRP effects were estimated separately for ads tagged with the Tips campaign website URL and 1-800-QUIT-NOW. RESULTS: In the average media market, an increase of 100 television GRPs per week for ads tagged with the Tips campaign website URL was associated with an increase of 650 unique visitors (P<.001), 769 total visits (P<.001), and 1255 total page views (P<.001) per week. The associations between GRPs for ads tagged with 1-800-QUIT-NOW and each Web traffic measure were also statistically significant (P<.001), but smaller in magnitude. CONCLUSIONS: Based on these findings, we estimate that the 16-week 2013 Tips television campaign generated approximately 660,000 unique visitors, 900,000 total visits, and 1,390,000 page views for the Tips campaign website. These findings can help campaign planners forecast the likely impact of targeted advertising efforts on consumers' use of campaign-specific websites. PMID- 26887958 TI - Evaluation of an antenatal acupuncture intervention as an adjunct therapy for antenatal depression (AcuAnteDep): study protocol for a pragmatic randomised controlled trial. AB - BACKGROUND: Depressed pregnant women face difficulty navigating a course between the potentially serious consequences of leaving depression untreated and significant limitations associated with conventional therapies, such as foetal toxicity and teratogenicity. Preliminary evidence is suggestive that acupuncture may provide a safe and effective alternative treatment option for antenatal depression; however, additional research is required. The purpose of this study is to further investigate this treatment possibility, with an additional examination of a potential biomechanistic acupuncture effect. METHODS/DESIGN: In this pragmatic randomised controlled trial, we will compare individually tailored, flexible antenatal depression-oriented acupuncture with equivalent attention progressive muscle relaxation and routine antenatal depression hospital care. Eligible women at 24 weeks of gestation with Edinburgh Postnatal Depression Scale scores of 13 or more will be recruited from 2 antenatal clinics in South Western Sydney, Australia. The recruitment goal of 96 is powered to demonstrate a significant difference in Edinburgh Postnatal Depression Scale score severity between acupuncture and usual care, with intervention groups receiving weekly 1-h treatments for 8 weeks from 24 to 31 weeks of gestation. Mental health and quality-of-life assessments will occur at study commencement, intervention weeks 4 and 8 and 6 weeks post-natally via the collection of completed Edinburgh Postnatal Depression Scale scores, Depression, Stress and Anxiety Scale scores and World Health Organisation Quality of Life Scale scores. Adjustment to mothering will also be evaluated at 6 weeks post-natally using the Being a Mother Scale. A putative biomechanistic effect of acupuncture on the oxytocinergic system will additionally be examined by comparing baseline salivary hormone levels with those measured at intervention weeks 4 and 8, as well as leucocyte oxytocin receptor expression at baseline and intervention week 8. DISCUSSION: Ethical approval was received in February 2015, and recruitment is underway and expected to be completed in July 2016. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000250538, Registered on 19 March 2015. PMID- 26887962 TI - A review on ethnobotany, pharmacology and phytochemistry of Tabernaemontana corymbosa. AB - OBJECTIVES: Tabernaemontana is a genus from the plant family, Apocynaceae with vast medicinal application and widespread distribution in the tropics and subtropics of Africa, Americas and Asia. The objective of this study is to critically evaluate the ethnobotany, medicinal uses, pharmacology and phytochemistry of the species, Tabernaemontana corymbosa (Roxb. ex Wall.) and provide information on the potential future application of alkaloids isolated from different parts of the plant. KEY FINDINGS: T. corymbosa (Roxb. ex Wall.) parts are used as poultice, boiled juice, decoctions and infusions for treatment against ulceration, fracture, post-natal recovery, syphilis, fever, tumours and orchitis in Malaysia, China, Thailand and Bangladesh. Studies recorded alkaloids as the predominant phytochemicals in addition to phenols, saponins and sterols with vast bioactivities such as antimicrobial, analgesic, anthelmintic, vasorelaxation, antiviral and cytotoxicity. SUMMARY: An evaluation of scientific data and traditional medicine revealed the medicinal uses of different parts of T. corymbosa (Roxb. ex Wall.) across Asia. Future studies exploring the structure bioactivity relationship of alkaloids such as jerantinine and vincamajicine among others could potentially improve the future application towards reversing anticancer drug resistance. PMID- 26887961 TI - Genomic and transcriptomic comparison of nucleotide variations for insights into bruchid resistance of mungbean (Vigna radiata [L.] R. Wilczek). AB - BACKGROUND: Mungbean (Vigna radiata [L.] R. Wilczek) is an important legume crop with high nutritional value in South and Southeast Asia. The crop plant is susceptible to a storage pest caused by bruchids (Callosobruchus spp.). Some wild and cultivated mungbean accessions show resistance to bruchids. Genomic and transcriptomic comparison of bruchid-resistant and -susceptible mungbean could reveal bruchid-resistant genes (Br) for this pest and give insights into the bruchid resistance of mungbean. RESULTS: Flow cytometry showed that the genome size varied by 61 Mb (mega base pairs) among the tested mungbean accessions. Next generation sequencing followed by de novo assembly of the genome of the bruchid resistant recombinant inbred line 59 (RIL59) revealed more than 42,000 genes. Transcriptomic comparison of bruchid-resistant and -susceptible parental lines and their offspring identified 91 differentially expressed genes (DEGs) classified into 17 major and 74 minor bruchid-resistance-associated genes. We found 408 nucleotide variations (NVs) between bruchid-resistant and -susceptible lines in regions spanning 2 kb (kilo base pairs) of the promoters of 68 DEGs. Furthermore, 282 NVs were identified on exons of 148 sequence-changed-protein genes (SCPs). DEGs and SCPs comprised genes involved in resistant-related, transposable elements (TEs) and conserved metabolic pathways. A large number of these genes were mapped to a region on chromosome 5. Molecular markers designed for variants of putative bruchid-resistance-associated genes were highly diagnostic for the bruchid-resistant genotype. CONCLUSIONS: In addition to identifying bruchid-resistance-associated genes, we found that conserved metabolism and TEs may be modifier factors for bruchid resistance of mungbean. The genome sequence of a bruchid-resistant inbred line, candidate genes and sequence variations in promoter regions and exons putatively conditioning resistance as well as markers detecting these variants could be used for development of bruchid-resistant mungbean varieties. PMID- 26887963 TI - Associative and Implicit Memory Performance as a Function of Cognitive Reserve in Elderly Adults with and without Mild Cognitive Impairment. AB - This study aims to analyze implicit and explicit memory performance as a function of cognitive reserve (CR) in a healthy control group (N = 39) and a mild cognitive impairment (MCI) group (N = 37). Both groups were subdivided into high and low cognitive reserve, and were asked to complete an explicit and implicit associative recognition tasks. The results showed that the control group was able to learn both tasks (eta2 = .19, p < .0001), and the high CR group fared better (eta2 = .06, p < .05). The MCI sample, conversely, was unable to learn the implicit relationship, and showed very little learning on the explicit association task. Participants diagnosed with MCI showed little plasticity in learning associations regardless of CR (eta2 = .12, p < .01). PMID- 26887964 TI - Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the small intestine in mice. AB - T cells of the small intestine, including Th17 cells, are critically involved in host protection from microbial infection, and also contribute to the pathogenesis of small bowel inflammatory disorders. Accumulating evidence suggests that mesenteric lymph nodes (MLNs) play important roles in gut-tropic T-cell generation, although it is still unclear if MLNs are involved in the pathogenesis of small intestine inflammation. To address this issue, we analyzed the roles of both MLNs and Peyer's patches (PPs) by evaluating MLN- or PP-deficient mice in an experimental model of small intestine inflammation, induced by CD3-specific mAb injection. Interestingly, MLNs, but not PPs, were essential for the pathogenesis of intestinal inflammation, in particular the accumulation and infiltration of CD4(+) T-cell populations, including Th17 cells, from the blood. In addition, CD4(+) T-cell accumulation was dependent on the function of the alpha4 beta7 integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral alpha4 beta7 (+) CD4(+) effector memory T cells under normal conditions, suggesting that MLNs may play a role in maintaining the number of gut tropic CD4(+) effector memory T cells circulating in the blood. Taken together, the present study highlights the important role of MLNs in contributing to the pathogenesis of small intestine inflammation. PMID- 26887965 TI - Water fluoridation and ethnic inequities in dental caries profiles of New Zealand children aged 5 and 12-13 years: analysis of national cross-sectional registry databases for the decade 2004-2013. AB - BACKGROUND: Gross and important inequities have historically existed in the oral health profiles of New Zealand children. Following the New Zealand Government's strategic oral health vision, launched in 2006, nationally collected information from 2004 to 2013 was used to analyze patterns in the prevalence of no obvious decay experience (caries-free) and mean decayed-missing-filled teeth indices over time and by community water fluoridation (CWF) and ethnic classifications in New Zealand children aged 5 years and in school year 8 (generally aged 12-13 years). METHODS: National aggregated data collected from children's routine child oral health service dental examinations were retrieved, and combined with demographic information from Statistics New Zealand. Children's CWF status was defined by the public water supply status of their school. Crude and standardized population estimates of caries-free prevalence and mean decayed-missing-filled teeth indices over time were derived. Unweighted linear regression models of main effects and two-factor interactions were investigated by age group. RESULTS: Dental examination data were available from 417,318 children aged 5 years and 471,333 year 8 children; of whom 93,715 (22.5 %) and 94,001 (19.9 %), respectively, were Maori. Dental examination coverage of Maori children was significantly less than their non-Maori counterparts (approximately 11 % and 14 % for aged 5 and year 8 children, respectively). Regression analysis revealed that caries-free prevalence and mean decayed-missing-filled teeth indices significantly improved over the study period for both age groups. Significant and sustained differences were observed between Maori and non-Maori children, and between CWF and non-CWF exposed groups. However, a convergence of dental profiles between non-Maori children in CWF and non-CWF regions was observed. DISCUSSION: Significant and important gains in New Zealand children's oral health profiles appear to have been made over the last decade. Maori children continued to carry a disproportionate oral health burden, even for those in CWF regions. The apparent profile convergence between non-Maori children in CWF and non-CWF regions is noteworthy; although a likely consequence of demographic shifts and unmeasured confounders. CONCLUSIONS: CWF itself did not remove disparities in caries levels between Maori and non-Maori children. Multiple, multi-pronged strategies are needed that overcome the array of factors which disadvantage Maori. PMID- 26887967 TI - Genotyping of infectious bronchitis viruses from broiler farms in Iraq during 2014-2015. AB - Infectious bronchitis virus (IBV) is one of the most critical pathogens in the poultry industry, causing serious economic losses in all countries including Iraq. IBV has many genotypes that do not confer any cross-protection. This virus has been genotyped by sequence analysis of the S1 glycoprotein gene. A total of 100 tracheal and kidney tissue specimens from different commercial broiler flocks in the middle and south of Iraq were collected from September 2013 to September 2014. Thirty-two IBV-positive samples were selected from among the total and were further characterized by nested PCR. Phylogenetic analysis revealed that isolates belong to four groups (group I, variant 2 [IS/1494-like]; group II, 793/B-like; group III, QX-like; group IV, DY12-2-like). Sequence analysis revealed nucleotide sequence identities within groups I, II, and III of 99.68 %-100 %, 99.36 %-100 %, and 96.42 %-100 %, respectively. Group I (variant 2) was the dominant IBV genotype. One Chinese-like recombinant virus (DY12-2-like) that had not been reported in the Middle East was detected. In addition, the presence of QX on broiler chicken farms in the area studied was confirmed. This is the first comprehensive study on the genotyping of IBV in Iraq with useful information regarding the molecular epidemiology of IBV. The phylogenetic relationship of the strains with respect to different time sequences and geographical regions displayed complexity and diversity. Further studies are needed and should include the isolation and full-length molecular characterization of IBV in this region. PMID- 26887966 TI - Bioavailability of tomato polyphenols is enhanced by processing and fat addition: Evidence from a randomized feeding trial. AB - SCOPE: Tomato contains a variety of phenolics associated with health-promoting properties. However, the effects of processing and the addition of oil during tomato sauce preparation on microbial metabolism of phenolics in the small intestine are still unclear. METHODS AND RESULTS: An open, controlled, randomized, and crossover feeding trial with 40 healthy volunteers was carried out to analyze the metabolites in plasma and urine after the consumption of tomato and tomato sauces, with tomato sauce enriched with refined olive oil (ROOE) and without refined olive oil (oil-free: OF). Ten phenolics in plasma and 93 metabolites in urine were quantified. Processing tomatoes into sauce enhanced the bioavailability of flavanones, flavanols, and some hydroxycinnamic acids, as reflected by the increase in the area under the plasma concentration versus time curve. An increase in their plasma half-life was also observed, particularly after ingestion of ROOE, possibly favored by enterohepatic circulation. A wide variety of gut microbial metabolites was also detected, namely flavanones, hydroxycinnamic acids, flavonols, hydroxyphenylpropanoic acids, hydroxyphenylacetic acids, and hydroxybenzoic acids. CONCLUSIONS: Flavanones and flavonols in ROOE presented higher bioavailability, suggesting that the processing undergone by the raw tomato improved their absorption. PMID- 26887968 TI - Differences in the epidemiology and virology of mild, severe and fatal human infections with avian influenza A (H7N9) virus. AB - A novel avian influenza A (H7N9) virus caused 5-10 % mild and 30.5 % fatal human infections as of December 10, 2015. In order to investigate the reason for the higher rate of fatal outcome of this infection, this study compared the molecular epidemiology and virology of avian influenza A (H7N9) viruses from mild (N = 14), severe (N = 50) and fatal (N = 35) cases, as well as from non-human hosts (N = 73). The epidemiological results showed that the average age of the people in the mild, severe and fatal groups was 27.6, 52 and 62 years old, respectively (p < 0.001). Males accounted for 42.9 % (6/14), 58.0 % (29/50), and 74.3 % (26/35) of cases in the mild, severe and fatal group respectively (p = 0.094). Median days from onset to start of antiviral treatment were 2, 5 and 7 days in the mild, severe and fatal group, respectively (p = 0.002). The median time from onset to discharge/death was 12, 40 and 19 days in the mild, severe and fatal group, respectively (p < 0.001). Analysis of whole genome sequences showed that PB2 (E627K), NA (R294K) and PA (V100A) mutations were markedly associated with an increased fatality rate, while HA (N276D) and PB2 (N559T) mutations were clearly related to mild cases. There were no differences in the genotypes, adaptation to mammalian hosts, and genetic identity between the three types of infection. In conclusion, advanced age and delayed confirmation of diagnosis and antiviral intervention were risk factors for death. Furthermore, PB2 (E627K), NA (R294K) and PA (V100A) mutations might contribute to a fatal outcome in human H7N9 infection. PMID- 26887970 TI - S segment variability during the two first years of the spread of Schmallenberg virus. AB - A large sheep flock screened over a two-year period showed active spreading of Schmallenberg virus (SBV) during the summers of 2011 and 2012. Transplacental infections were observed during the two associated lambing periods (the winters of 2012 and 2013). Analysis of small (S) segment sequences of 38 SBV-positive samples, collected during periods of viral spreading and lambing revealed intra herd sequences diversity and sub-consensus variability occurring after transplacental infections. In comparison with the nucleoprotein (N), which appeared to be conserved, the non-structural protein (NSs) showed the highest level of variability at the time of viral emergence and over the two-year analysis period. PMID- 26887969 TI - Full-length M and L RNA sequences of tospovirus isolate 2009-GZT, which causes necrotic ringspot on tomato in China. AB - The virus isolate 2009-GZT, collected from tomato in Guizhou province of China, was identified as a new member of the genus Tospovirus based on its S RNA sequence. Because its provisional name, "tomato necrotic spot virus" (TNSV), was identical to an already existing member of the genus Ilarvirus, 2009-GZT was renamed "tomato necrotic spot-associated virus" (TNSaV). In this study, the full length sequences of the genomic M and L RNAs of TNSaV were determined and analyzed. The M RNA has 4,773 nucleotides (nt), encoding the NSm protein of 309 aa (34.4 kDa) in the viral (v) strand and the glycoprotein precursor (Gn/Gc) of 1123 aa (128 kDa) in the viral complementary (vc) strand. The NSm and Gn/Gc of TNSaV share the highest aa sequence identity (86.2 % and 86.9 %, respectively) with those of tomato zonate spot virus. The L RNA contains 8,908 nt and codes for the putative RNA-dependent RNA polymerase (RdRp) of 2885 aa (332 kDa) in the vc strand. The RdRp of TNSaV shares the highest aa sequence identity (85.2 %) with that of calla lily chlorotic spot virus (CCSV). Serological assays showed that TNSaV cross-reacts with rabbit antisera against watermelon silver mottle virus (WSMoV) NP and CCSV NP, indicating that TNSaV is a member of the WSMoV serogroup. PMID- 26887971 TI - One-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) for detection of tomato torrado virus. AB - 'Torrado' disease caused by tomato torrado virus (ToTV) is responsible for considerable losses in tomato production. Therefore, a one-step reverse transcription loop-mediated isothermal amplification protocol for early and fast detection of ToTV isolates has been developed. The RNA extracted from ToTV infected plants was tested using this protocol with a set of six primers specific for the Vp35 coat protein gene sequence. The amplified products were analyzed using amplification curves, electrophoresis, and direct staining of DNA. The sensitivity of the protocol was tenfold higher than that of conventional RT-PCR. This new protocol is inexpensive, rapid, simple, and very sensitive. PMID- 26887972 TI - Molecular genetic characterization of rabies virus glycoprotein gene sequences from rabid dogs in Bangkok and neighboring provinces in Thailand, 2013-2014. AB - Because of its association with dogs, rabies virus (RABV) is still endemic in Thailand, where it is a serious public health problem. The genetic characterization of RABV in Thailand is limited. Therefore, in this study, we investigated the molecular epidemiology and genetic diversity of RABV in the endemic area. Viral RNA from 48 brain specimens from rabid dogs, collected in Bangkok and seven neighboring provinces in 2013-2014, was extracted and sequenced. The complete rabies glycoprotein (G) gene sequences (1575 nt) were aligned, and a phylogenetic analysis was performed using the maximum-likelihood method. All of the Thai rabies virus isolates belonged to lyssavirus genotype 1 and clustered in the same lineage as isolates from South East Asia (SEA) and China. The Thai rabies virus isolates formed two distinct clades, THA-1 and THA 2. Clade THA-1 was the predominant clade and could be divided into two subclades, THA-1A and THA-1B. Clade THA-2 was closely associated with human Thai isolates collected in a previous study. The overall mean rate of evolution based on the G gene was approximately 1.56 * 10(-4) substitutions/site/year. The genetic identities among the isolates from Thailand and other SEA countries were >88.4 % at the nucleotide sequence level and 95 % at the amino acid sequence level. The deduced amino acid sequences of the G proteins of the RABV isolates were compared. A single amino acid change (N194T) in subclade THA-1A distinguished the Thai RABV isolates from other RABV isolates. Our results suggest that these Thai dog RABV isolates share a common ancestor with the RABV isolates circulating in the endemic regions of SEA countries and China. Furthermore, there were strong genetic relationship to RABV from Cambodia, Vietnam and Laos. These data extend our understanding of the relatedness and genetic variation of RABV in Thailand. PMID- 26887973 TI - Short-Term Effects of TNF Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis. AB - TNFalpha inhibitors (TNFalphaI) exert positive effects on disease activity in rheumatoid arthritis (RA). Bone involvement is a major determinant of functional impairment in this disease. Here we investigated the short-term effects of TNFalphaI therapy on bone metabolism and density. We studied 54 patients with RA starting a TNFalphaI biologic drug, in whom any factor known to interfere with bone metabolism was excluded or rigorously accounted for. We measured at baseline and after 6-month therapy bone turnover markers: N-propeptide of type I collagen (P1NP), and bone alkaline phosphates for bone formation and serum C-terminal telopeptide of type I collagen (CTX) for bone resorption. We also evaluated bone mineral density (BMD) at hip and lumbar by dual-energy X-ray absorptiometry. All bone markers rose significantly and these changes were not dependent on steroid dosage. A significant decrease in femoral neck BMD was also observed. These results indicate that TNFalphaI therapy in RA over 6 months is associated with an early increase in bone turnover and a decline in hip BMD. PMID- 26887974 TI - Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression. AB - Bone remodeling can be disturbed in active rheumatoid arthritis (RA), possibly as a result of elevated levels of circulating inflammatory cytokines. Osteocyte specific proteins and cytokines play a vital role in bone remodeling by orchestrating bone formation and/or bone resorption. Therefore, we aimed to investigate the effect of RA-serum or inflammatory cytokines on expression of human osteocyte-specific proteins and cytokines. Human trabecular bone chips were cultured with RA-serum or inflammatory cytokines for 7-days. Live-dead staining was performed to assess cell viability. Gene expression of osteocyte-specific proteins and cytokines was analyzed by qPCR. Immuno-staining was performed for osteocyte-specific markers. Approximately 60 % of the osteocytes on the bone chips were alive at day-7. Cells in or on the bone chips did express the gene for osteocyte markers SOST, FGF23, DMP1, and MEPE, and the cytokines IL-1beta, IL-6, and TNFalpha at day 0 and 7. Active RA-serum treatment enhanced IL-1beta, TNFalpha, SOST, and DKK1 gene expression. IL-1beta treatment enhanced IL-1beta, TNFalpha, IL-6, IL-8, FGF23, and SOST gene expression. TNFalpha treatment enhanced IL-1beta, TNFalpha, IL-6, IL-8, and FGF23 gene expression. IL-8 treatment enhanced TNFalpha, IL-8, and FGF23 gene expression. A combination of IL 1beta, IL-6, and TNFalpha treatment synergistically upregulated IL-1beta, IL-6, and IL-8 gene expression, as well as enhanced TNFalpha, OPG, SOST, and FGF23, and inhibited DKK1 gene expression. In conclusion, gene expression of human osteocyte specific proteins and cytokines was affected by RA-serum, and exogenous recombinant cytokines treatment suggesting that osteocytes could provide a new target to prevent systemic inflammation-induced bone loss in RA. PMID- 26887976 TI - Inference on treatment-covariate interaction based on a nonparametric measure of treatment effects and censored survival data. AB - The investigation of the treatment-covariate interaction is of considerable interest in the design and analysis of clinical trials. With potentially censored data observed, non-parametric and semi-parametric estimates and associated confidence intervals are proposed in this paper to quantify the interactions between the treatment and a binary covariate. In addition, comparison of interactions between the treatment and two covariates are also considered. The proposed approaches are evaluated and compared by Monte Carlo simulations and applied to a real data set from a cancer clinical trial. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26887975 TI - Synergistic anti-oral cancer effects of UVC and methanolic extracts of Cryptocarya concinna roots via apoptosis, oxidative stress and DNA damage. AB - Purpose Radiation combined with natural products may improve the radiosensitivity of cancer cells. This study investigated the potential of a combined modality treatment with Ultraviolet C (UVC; wavelength range 200-280 nm) and our previously identified anti-oral cancer agent (methanolic extracts of Cryptocarya concinna roots; MECCrt) in oral cancer cells. Materials and methods The mechanism of the possible synergy of UVC and MECCrt was explored in terms of cell viability, cell cycle, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MitoMP), and DNA damage analyses. Results In cell viability (%) at 24 h treatment, the low doses of UVC (14 J/m(2)) and MECCrt (10 MUg/ml) resulted in slight damage to human oral cancer Ca9-22 cells (83.2 and 80.4) but was less harmful to human oral normal HGF-1 cells (93.4 and 91.8, respectively). The combined treatment of UVC and MECCrt (UVC/MECCrt) had a lower viability (54.5%) than UVC or MECCrt alone in Ca9-22 cells but no showed significant change in HGF-1 cells. In Ca9-22 cells, the expression of flow cytometry-based apoptosis (sub-G1 phase, annexin V, and pancaspase assays) was significantly higher in UVC/MECCrt than in UVC or MECCrt alone (p < 0.0001). Using flow cytometry, intracellular ROS levels of UVC/MECCrt and MECCrt alone were higher than for UVC alone. MitoMP change and H2A histone family member X (gammaH2AX; H2AFX)-based DNA damage were synergistically inhibited and induced by MECCrt/UVC compared to its single treatment in Ca9-22 cells, respectively. Conclusion UVC plus MECCrt treatment had selective killing and synergistic anti-proliferative effects against oral cancer cells involving apoptosis, oxidative stress, and DNA damage. This combination therapy appears to have a great clinical potential against oral cancer cells. PMID- 26887978 TI - Short Communication: Hyperthyroidism in Human Immunodeficiency Virus Patients on Combined Antiretroviral Therapy: Case Series and Literature Review. AB - We describe an HIV-infected patient initiated on combined antiretroviral therapy (cART) who subsequently developed immune restoration disease (IRD) hyperthyroidism-this case represents one of five such patients seen at our center within the past year. Similar to previous reports of hyperthyroidism due to IRD, all of our patients experienced a rapid early recovery in total CD4 count, but developed symptoms of hyperthyroidism on average 3 years (38 months) after beginning cART, which represents a longer time frame than previously reported. Awareness and recognition of this potential complication of cART, which may occur years after treatment initiation, will allow patients with immune restorative hyperthyroidism to receive timely therapy and avoid the long-term complications associated with undiagnosed thyroid disease. PMID- 26887979 TI - Congratulations to the 2016 JALA Ten! PMID- 26887977 TI - GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification. AB - Epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, has been implicated to contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). Here we report that a transcription factor--Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. EOC tumours with lower GRHL2 levels are associated with the Mes/Mesenchymal molecular subtype and a poorer overall survival. shRNA mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype results in EMT changes, with increased cell migration, invasion and motility. By ChIP sequencing and gene expression microarray, microRNA-200b/a is identified as the direct transcriptional target of GRHL2 and regulates the epithelial status of EOC through ZEB1 and E-cadherin. Our study demonstrates that loss of GRHL2 increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding sites at miR 200b/a and E-cadherin genes. These findings support GRHL2 as a pivotal gatekeeper of EMT in EOC via miR-200-ZEB1. PMID- 26887980 TI - JALA Special Issue: High-Throughput Imaging. PMID- 26887981 TI - High serum HCV RNA in chronic hepatitis C patients coinfected with HIV despite successful antiretroviral therapy. AB - BACKGROUND: Baseline serum HCV RNA predicts treatment success in chronic hepatitis C patients. Thresholds at 0.8, 2, 4 and 6 million IU/ml discriminate treatment outcomes using distinct antiviral regimens. Compared to the general population, immunosuppressed individuals exhibit greater viral load values. This has been confirmed in HIV-HCV-coinfected patients, although little is known about the influence of antiretroviral therapy. METHODS: Serum HCV RNA results recorded from all chronic hepatitis C patients who consecutively attended at our clinic were analysed. RESULTS: A total of 813 patients with detectable HCV RNA were identified. HIV coinfection was present in 78.7%, of whom 91% were on antiretroviral therapy. Overall, 467 (57%), 273 (34%), 170 (21%) and 127 (16%) had HCV RNA >0.8, >2, >4 and >6 million IU/ml, respectively. These high viral load values were found in 60%/36%/23%/18% of HIV-positive versus 47%/25%/11%/6% of HIV-negative individuals (P<0.01), respectively. In multivariate analysis, the greatest HCV RNA values were only significantly associated with HIV coinfection and HCV genotypes-1 or -4. Greater HCV RNA values were paradoxically found in HIV patients on than off antiretroviral therapy. CONCLUSIONS: Serum HCV RNA values above 0.8, 2, 4 and 6 million IU/ml are roughly seen in 47%, 25%, 11% and 6% of chronic hepatitis C monoinfected patients, respectively. Despite being on antiretroviral therapy, the corresponding figures are 1.3- to 3.0-fold greater in HIV-HCV-coinfected patients, who may benefit less frequently from shorter oral HCV treatment lengths. PMID- 26887983 TI - The RelA/cRel nuclear factor-kappaB (NF-kappaB) dimer, crucial for inflammation resolution, mediates the transcription of the key enzyme in melatonin synthesis in RAW 264.7 macrophages. AB - Lipopolysaccharide (LPS) modulates the transcription of the gene that codifies the enzyme arylalkylamine-N-acetyltransferase (AA-NAT) through nuclear translocation of the transcription factor nuclear factor-kappa-light-chain enhancer of activated B cells (NF-kappaB). AA-NAT converts serotonin to N acetylserotonin, the ultimate precursor of melatonin. Activation of kappa B elements (aa-nat-kappaB), localized in the promoter (nat-kappaB1 and nat kappaB2), leads to Aa-nat transcription in RAW 264.7 macrophages. Competitive electrophoretic mobility shift assay (EMSA) with oligonucleotide probes corresponding to each of the two elements, as well as a NF-kappaB consensus corresponding probe, revealed different specificities for each kappaB element. In addition, activator protein-1 (AP-1) as well as signal transducers and activator of transcription-1 and 3 (STAT-1; STAT-3) competed with NF-kappaB for binding to nat-kappaB1, while only STAT-3 competed with NF-kappaB for binding to nat kappaB2. According to co-immunoprecipitation (ChiP) assays, these two sites are able to distinguish NF-kappaB subunits. The sequence nat-kappaB1 bound dimers containing p52, RelA, and cRel, while nat-kappaB2 bound preferentially p50, p52, and RelA, and did not bind cRel. The expression of RelA and cRel is essential for the induction of Aa-nat expression and melatonin synthesis. Considering that the expression of cRel is induced by the earlier expressed p50/RelA, the differential effects of NF-kappaB dimers may be intimately associated with the temporal regulation of inflammatory responses, with the resolution phase being associated with paracrine and autocrine melatonin effects. Such data suggest that the proven effects of exogenous melatonin in the resolution phase of inflammation are paralleled by the effects of locally synthesized melatonin in immune cells. PMID- 26887982 TI - The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-gamma and CB2 pathways. AB - Scleroderma is a group of rare diseases associated with early and transient inflammation and vascular injury, followed by fibrosis affecting the skin and multiple internal organs. Fibroblast activation is the hallmark of scleroderma, and disrupting the intracellular TGFbeta signaling may provide a novel approach to controlling fibrosis. Because of its potential role in modulating inflammatory and fibrotic responses, both PPARgamma and CB2 receptors represent attractive targets for the development of cannabinoid-based therapies. We have developed a non-thiophilic and chemically stable derivative of the CBD quinol (VCE-004.8) that behaves as a dual agonist of PPARgamma and CB2 receptors, VCE-004.8 inhibited TGFbeta-induced Col1A2 gene transcription and collagen synthesis. Moreover, VCE-004.8 inhibited TGFbeta-mediated myofibroblast differentiation and impaired wound-healing activity. The anti-fibrotic efficacy in vivo was investigated in a murine model of dermal fibrosis induced by bleomycin. VCE-004.8 reduced dermal thickness, blood vessels collagen accumulation and prevented mast cell degranulation and macrophage infiltration in the skin. These effects were impaired by the PPARgamma antagonist T0070907 and the CB2 antagonist AM630. In addition, VCE-004.8 downregulated the expression of several key genes associated with fibrosis, qualifying this semi-synthetic cannabinoid as a novel compound for the management of scleroderma and, potentially, other fibrotic diseases. PMID- 26887984 TI - Behcet's disease in children, an overview. AB - BD is a systemic inflammatory disease with a variable vasculitis. Paediatric onset is very rare and carries a strong genetic component. Oral ulcers and fever of unknown origin are frequent at onset and difficult to distinguish from other inflammatory disorders; therefore, expert opinion is still mandatory to recognize the disease early. An international expert consensus has recently proposed new classification criteria for children with BD. The clinical spectrum of BD is heterogeneous and influenced by gender, ethnicity and country of residence. Young males have the worst prognosis with significantly more frequent neurological, ocular and vascular involvement. BD treatment is aimed at alleviating inflammation. Among all drugs, TNFalpha inhibitors have become a standard to control severe ocular, neurological and digestive system involvement. PMID- 26887985 TI - Prognostic role of urinary collecting system invasion in renal cell carcinoma: a systematic review and meta-analysis. AB - The relationship between urinary collecting system invasion (UCSI) and oncological outcomes in renal cell carcinoma (RCC) patients has attracted extensive attention recent years. However, the reports were inconsistent and remain controversial. Thus, we performed a systematic literature search of PubMed, Embase, Web of Science and The Cochrane Library databases to identify relevant studies up to June 2015 and conducted a standard meta-analysis of survival outcomes. 17 studies containing 9012 RCC patients satisfied the inclusion criteria. Pooled HRs for overall survival (OS) and recurrence-free survival (RFS) were 1.45 (95%CI, 1.26-1.66, P < 0.001) and 2.27 (95% CI, 1.54 3.34, P < 0.001), respectively. Further subgroup analysis suggested that UCSI was significant associated with poor cancer-specific survival (CSS) in stage T1-T2 RCC (HR = 2.05, 95%CI: 1.43-2.96, P < 0.001) but not in stage T3-T4 tumors (HR = 1.08, 95%CI: 0.63-1.85, P = 0.771). Current evidence revealed that UCSI has a significant negative impact on OS and RFS in RCC patients and could be used to predict CSS especially in localized RCC. Thus, RCC patients with UCSI should be paid more attention by clinician and pathologist and require close follow up for their poor prognosis. PMID- 26887986 TI - Quantitative accuracy of (177)Lu SPECT reconstruction using different compensation methods: phantom and patient studies. AB - BACKGROUND: In targeted radionuclide therapy (TRT), accurate quantification using SPECT/CT images is important for optimizing radiation dose delivered to both the tumour and healthy tissue. Quantitative SPECT images are regularly reconstructed using the ordered subset expectation maximization (OSEM) algorithm with various compensation methods such as attenuation (A), scatter (S) and detector and collimator response (R). In this study, different combinations of the compensation methods are applied during OSEM reconstruction and the effect on the (177)Lu quantification accuracy is studied in an anthropomorphic torso phantom. In addition, the phantom results are reflected to (177)Lu-DOTA-Tyr3-octreotate ((177)Lu-DOTATATE)-treated patient data and kidney absorbed dose estimates. METHODS: The torso phantom was imaged with nine various sized (0.4-104.4 cm(3)) spherical inserts, filled with known (177)Lu activity ranging from 0.5 to 105.5 MBq. Images were reconstructed using OSEM algorithm using A, AR and ARS compensation method combinations. The compensation method combinations were compared by calculating the concentration recovery coefficient (cRC) for each insert. In addition, ten (177)Lu-DOTATATE-treated patient's post-therapy dosimetry acquisitions were reconstructed, and the absorbed dose to kidneys was estimated. RESULTS: cRC values depend on the insert size for all compensation methods. AR and ARS produced significantly higher cRC values than attenuation correction alone. There were no cRC value differences between the methods for the smallest 1-cm-diameter insert, cRC being 0.18. However, the collimator and detector response compensation method (R) made the 1.3-cm-diameter insert clearly visible and improved cRC estimate from 0.19 to 0.43. ARS produced slightly higher cRC values for small- and medium-sized inserts than AR. On the patient data, a similar trend could be seen. AR and ARS produced higher kidney activities than using attenuation correction alone; the total absorbed doses to the right and left kidneys were on average 15 and 20 % higher for AR and 19 and 25 % higher for ARS, respectively. The effective half-life decay estimated from time-activity curves however showed no notable difference between the compensation methods. CONCLUSIONS: The highest cRC values were achieved by applying ARS compensation during reconstruction. The results were notably higher than those using attenuation correction alone. Similarly, higher activity estimates and thus higher absorbed dose estimates were found in patient data when all compensation methods were applied. ARS improved cRC especially in small-sized sources, and it thus might aid tumour dosimetry for (177)Lu PRRT treatments. PMID- 26887987 TI - Genome-wide transcriptional responses of Alteromonas naphthalenivorans SN2 to contaminated seawater and marine tidal flat sediment. AB - A genome-wide transcriptional analysis of Alteromonas naphthalenivorans SN2 was performed to investigate its ecophysiological behavior in contaminated tidal flats and seawater. The experimental design mimicked these habitats that either added naphthalene or pyruvate; tidal flat-naphthalene (TF-N), tidal flat-pyruvate (TF-P), seawater-naphthalene (SW-N), and seawater-pyruvate (SW-P). The transcriptional profiles clustered by habitat (TF-N/TF-P and SW-N/SW-P), rather than carbon source, suggesting that the former may exert a greater influence on genome-wide expression in strain SN2 than the latter. Metabolic mapping of cDNA reads from strain SN2 based on KEGG pathway showed that metabolic and regulatory genes associated with energy metabolism, translation, and cell motility were highly expressed in all four test conditions, probably highlighting the copiotrophic properties of strain SN2 as an opportunistic marine r-strategist. Differential gene expression analysis revealed that strain SN2 displayed specific cellular responses to environmental variables (tidal flat, seawater, naphthalene, and pyruvate) and exhibited certain ecological fitness traits -- its notable PAH degradation capability in seasonally cold tidal flat might be reflected in elevated expression of stress response and chaperone proteins, while fast growth in nitrogen-deficient and aerobic seawater probably correlated with high expression of glutamine synthetase, enzymes utilizing nitrite/nitrate, and those involved in the removal of reactive oxygen species. PMID- 26887988 TI - A 100 kHz Time-Resolved Multiple-Probe Femtosecond to Second Infrared Absorption Spectrometer. AB - We present a dual-amplifier laser system for time-resolved multiple-probe infrared (IR) spectroscopy based on the ytterbium potassium gadolinium tungstate (Yb:KGW) laser medium. Comparisons are made between the ytterbium-based technology and titanium sapphire laser systems for time-resolved IR spectroscopy measurements. The 100 kHz probing system provides new capability in time-resolved multiple-probe experiments, as more information is obtained from samples in a single experiment through multiple-probing. This method uses the high repetition rate probe pulses to repeatedly measure spectra at 10 us intervals following excitation allowing extended timescales to be measured routinely along with ultrafast data. Results are presented showing the measurement of molecular dynamics over >10 orders of magnitude in timescale, out to 20 ms, with an experimental time response of <200 fs. The power of multiple-probing is explored through principal component analysis of repeating probe measurements as a novel method for removing noise and measurement artifacts. PMID- 26887989 TI - Spatially Multiplexed Imaging: Fluorescence Correlation Spectroscopy for Efficient Measurement of Molecular Diffusion at Solid-Liquid Interfaces. AB - Fluorescence correlation spectroscopy (FCS) has become an important technique for the characterization of molecular dynamics, especially at interfaces. Fluorescence correlation spectroscopy provides both temporal and spatial resolution for measuring fast processes at equilibrium through analysis of noise in fluorescence intensities from the statistical fluctuations in a small number of molecules. The small molecular populations produce very low-level fluorescence signals, where time-averaging the fluorescence autocorrelation function is needed to generate reasonable signal-to-noise (S/N) ratios. Recently imaging cameras have been adapted to FCS measurements of molecular dynamics at interfaces (membranes and surfaces) through the use of electron-multiplying charge-coupled device (EM-CCD) detectors for acquisition of fluorescence from addressable areas on the detector. This approach provides a major advantage over traditional focused-spot FCS by allowing electronic control over the location and area of the acquired region on the sample surface. Imaging-FCS can also provide a spatial multiplexing advantage through its ability to measure intensity data from larger areas in parallel with no loss of time resolution. In this work, this multiplexing advantage is exploited to determine molecular diffusion rates from the simultaneous measurement of multiple areas on a surface, the autocorrelation traces from which are averaged to improve the S/N ratio. As proof of concept, the diffusion of 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI) on a C18-modified interface was measured using this multiplexed method and compared to autocorrelation data acquired from a single spot. Due to the slow thermal recovery of the EM-CCD that inhibits fast time-averaging, spatial multiplexing in imaging-FCS provides an eightyfold time savings to reach the same S/N ratio as multiple (time-averaged) measurements from a single spot. PMID- 26887990 TI - [What we have learned from the 25 years of endoscopic sinus surgery]. PMID- 26887991 TI - [Complications in endoscopic sinus surgery: prevention and management]. PMID- 26887992 TI - [Endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma: a review of 71 patients and analysis of the prognostic factors]. AB - OBJECTIVE: To evaluate the efficacy of endoscopic nasopharyngectomy in the management of recurrent nasopharyngeal cancers (NPC) and to identify the prognostic factors. METHODS: Between January 2006 and March 2014, 71 patients who received endoscopic nasopharyngectomy for recurrent NPC were retrospectively reviewed. The sex and the age of the patients, T stage, and tumor necrosis were recorded. Correlation between clinicopathological features and survival time was analyzed. Kaplan-Meier analysis was used to calculate the disease overall survival, disease-specific survival, and disease-free survival rates. Cox multivariate regression analysis and ROC curve analysis were used to determine the predictive value of the parameters. RESULTS: The median age of 71 patients with recurrent nasopharyngeal carcinoma was 51.0 years old. Male to female ratio was 2.9:1 (male: 53, female: 18). The lesions were staged as follows (AJCC, 2010, seventh edition): rT1, 27; rT2, 10; rT3, 19 and rT4, 15. All patients underwent successful endoscopic nasopharyngectomy. No patient was transferred to open approach. The mean operative time was 155 minutes. The average blood loss was 450 ml. Three patients needed intraoperative blood transfusion. No serious postoperative complications occurred. Postoperative follow-up time was 5-96 months. During follow-up, 48 cases survived, including that 7 patients survived with disease, 1 patient had pulmonary metastases, and 1 case had cervical lymph node metastasis. Two-year overall survival and disease-free survival rates were 74.0% and 60.5%, respectively. Five-year overall survival and disease-free survival rates were 39.0% and 31.9%, respectively. Multivariate analysis showed that tumor necrosis was an independent prognostic factor for survival in recurrent nasopharyngeal carcinoma patients (P=0.001). CONCLUSION: Endoscopic nasopharyngectomy is a safe and effective procedure for the treatment of recurrent nasopharyngeal carcinoma. PMID- 26887993 TI - [Analysis of clinical efficacy and the quality of life after endoscopic nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma]. AB - OBJECTIVE: To explore the clinical efficacy of patients who underwent endoscopic salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma (rNPC) after irradiation failure, and examine the quality of life (QOL) of them who were at different tumor stage and given different postoperative treatment. METHODS: Ninety-six patients who underwent endoscopic salvage nasopharyngectomy for rNPC between June 2009 and March 2015 were retrospectively reviewed. rTNM stage: 20 cases were at stage I, 16 at stage II, 44 at stage III, 16 at stage IV; rT1 22 cases (22.9%), rT2 16 cases (16.7%), rT3 42 cases (43.8%), rT4 16 cases (16.7%); rN0 92 cases (95.8%), rN1 2 cases (2.1%), rN2 2 cases (2.1%); No with distance metastasis. All the patients underwent endoscopic resection of lesions, and four cases with cervical metastasis received neck dissection at the same time.Postoperatively the self-reported, health-related QOL questionnaires were used to assess and compare the QOL of survival patients.SPSS 19.0 software was used to analyzed the data. RESULTS: The overall 1 year survival rates (SR), 2 year SR, 3 year SR were 83%, 68%, 63%, respectively. The median follow-up was 43 months. Cox regression analysis indicated the complete resection for rNPC and pathology were two independent factors affecting survival. The QOL of patients who received endoscopic salvage nasopharyngectomy only were better than the patients who received concurrent chemoradiation therapy or chemotherapy. CONCLUSIONS: The patients who underwent endoscopic salvage nasopharyngectomy for rNPC had a good survival rates and QOL. PMID- 26887994 TI - [Endoscopic transnasal orbital balanced decompression technique for severe Graves' orbitopathy]. AB - OBJECTIVE: To determine the efficacy of endoscopic transnasal orbital balanced decompression technique for the treatment of severe Graves' orbitopathy. METHODS: Six cases (12 eyes) of severe Graves'orbitopathy were included in this study. All patients were undergone endoscopic transnasal orbital balanced decompression technique (orbital inner and lower wall decompression+ lateral orbital decompression) for severe Graves'orbitopathy and serious affecting visual function or appearance. RESULTS: The follow-up ranged from 12 months to 2 years and 4 months. Postoperatively, the visual acuity markly improved from 0.23 +/- 0.08 to 0.48 +/- 0.13 (t=-5.749, P<0.001). Proptosis measured by exophthalmoter distictly reduced from (22.08 +/- 1.08) mm to (15.67 +/- 1.44) mm (t=17.924, P< 0.001). The palpebral fissures obviously reduced from (12.03 +/- 0.91) mm to (8.62 +/- 0.75) mm (t=9.600, P< 0.001), and orbital volume evidently increased from (26.84 +/- 0.62) cm3 to (31.56 +/- 1.10) cm3 (t=-16.567, P<0.001). Compared with the preoperative result, the orbital pressure was significantly decreased after operation (t=-6.759 (Y=100 g), t=-11.850 (Y=200 g), t=-6.189 (Y=300 g), P<0.001). Diplopia was appeared in 3 cases, and disappeared 3 to 5 months after surgery. CONCLUSION: Endoscopic transnasal orbital balanced decompression technique is effective for the treatment of severe Graves'orbitopathy. PMID- 26887995 TI - [Surgical anatomy, technique and application of endoscopic endonasal transpterygoid approach in skull base surgery]. AB - OBJECTIVE: To identify the landmarks of transpterygoid approach and to report its application in a series of cases. METHODS: Two silicon-injected adult cadaveric heads(4 sides) were dissected by performing an endoscopic endonasal transpterygoid approach after CT scanning for imaging guidance. High-quality pictures were obtained. This approach was used to treat twelve patients with skull base lesions including 3 spontaneous cerebrospinal fluid (CSF) leaks in the lateral recess of the sphenoid sinus, 2 neurofibromas and 2 Schwannomas involving the pterygopalatine fossa and infratemporal fossa, 1 dermoid cyst involving the middle fossa and infratemporal fossa, 1 invasive fungal sinusitis invading the middle fossa base, 1 basal cell adenoma in the upper parapharyngeal space, 1 chondrosarcoma in the parasellar region and 1 adenoid cystic carcinoma. Clinical records were reviewed. RESULTS: In terms of approach dissection, important landmarks, such as the sphenopalatine foramen and artery, vidian canal and nerve, foramen rotundum and maxillary branch of trigeminal nerve, foramen ovale and mandibular branch of trigeminal nerve, as well as pterygoid segment of Eustachian tube were identified. In terms of clinical data, three patients with spontaneous CSF leak underwent repair. Six patients with benign lesions underwent complete tumor resection. In the patient with invasive fungal disease, thorough debridement was undertaken and antifungal drug was administered for one month. For these benign skull base lesions, there was no recurrence during the follow-up period. In the patient with chondrosarcoma, most of the tumor was removed in the first operation, and was followed by two endoscopic operations because of fast growth of the tumor. Final control was achieved with chemotherapy and radiation. In the patient with adenoid cystic carcinoma, tumor recurred five years after surgery, and was reoperated. CONCLUSION: An understanding of the landmarks of the transpterygoid approach is paramount for surgically dealing with disease located within and adjacent to the region of the pterygoid process of the sphenoid bone. The endoscopic endonasal transpterygoid approach is feasible and safe in selected patients with skull base lesions. PMID- 26887996 TI - [Cinical and genetic characteristics of familial Meniere's disease: three families report]. AB - OBJECTIVE: To investigate the clinical and genetic characteristics of three Chinese Meniere's disease (MD) families and decipher the mechanism of MD further. METHODS: Personal and family medical evidence of hearing loss, vestibular symptoms, and other clinical abnormalities of the participants were identified, clinical and genetic features were analyzed. Targeted 307 genes capture and high throughput sequencing were performed on the two ascertained members of family 1007184. RESULTS: Eight patients from these three families showed post-lingual sensorineural hearing loss, six women and two men were involved. Age of onset in these affected members concentrated in the middle age, with the average age of 39.3 years old. Among them, patients from 1407278 were accompanied by migraine. All of the three probands presented as recurrent vertigo firstly, and then fluctuated hearing loss showed up, accompanying by tinnitus and ear fullness feeling. The hearing loss manifested as late-onset, low frequency-involved pattern, with subsequent gradual progression from moderate to severe level. Some of the patients progressed to severe level involving all frequencies at higher ages. In addition, most of the cases showed revitalization. Four cases received vestibular function tests, three of which had varying dysfunction of vestibular function, while the other one had normal vestibular function. Patients who had abnormal vestibular function showed much more severe hearing impairment. The three-generation family 1007193 had an autosomal recessive genetic characteristics, family 1007184 showed autosomal dominant inheritance of characteristics, family 1407278 were either autosomal dominant or X-linked dominant pattern. Through target genes capture high-throughput sequencing technology, we identified two candidate variants in the two members of family 1007184, named c. 2057G>A in EGFLAM and c. 1961C>T in ITGA8. CONCLUSION: Meniere's disease has some genetic and familial aggregation in Chinese population, but its complex genetic pathogenic mechanisms need further study. PMID- 26887997 TI - [High-resolution CT with multi-planar reformation in diagnosis of stapedial otosclerosis]. AB - OBJECTIVE: To evaluate the value of HRCT with multi-planar reformation (MPR) in the diagnosis of otosclerosis. METHODS: 138 ears in 129 patients with otosclerosis confirmed by surgery were evaluated retrospectively, using the MPR image along stapes as standard image, and 132 normal ears were collected as the control group. RESULTS: In the otosclerosis group, HRCT-MPR was positive in 108 ears, suspicious positive in 12 ears, and negative in 18 ears.In the control group, HRCT-MPR was positive in 4 ears, suspicious positive in 9 ears, and negative in 119 ears. The sensitivity for HRCT-MPR was 87.0% and the specificity was 90.2%. However, with 2 mm axial CT alone, the sensitivity was only 47.8%.The positive findings were mainly fenestral foci which related to stapes. CONCLUSIONS: HRCT-MPR showed high rate of sensitivity and specificity.We recommend the MPR image along stapes as standard image for otosclerosis diagnosis. PMID- 26887998 TI - [Effect of silencing HIF-1alpha by RNA interference on adhesion and invasion of the human nasopharyngeal carcinoma cell line CNE-1]. AB - OBJECTIVE: To investigate the effects of HIF-1alpha on adhesion and invasion of human nasopharyngeal carcinoma CNE-1 cells under hypoxia and underlying molecular mechanisms. METHODS: CoCl2was used to mimic tumor hypoxic microenvironment. mRNA and protein expressions of HIF-1alpha, E-cadherin and CXCR4 in CNE-1 cells at different hypoxic time phases were detected by RT-PCR and ELISA respectively. The influences of silencing HIF-1alpha using RNA interference on E-cadherin and CXCR4 expressions were evaluated. Adhesion test Transwell invasion test were used to evaluate the effects of HIF-1alpha gene silencing on cell adhesion and invasion. RESULTS: Under hypoxia, HIF-1alpha mRNA expression in CNE-1 cells was stable, but its protein expression increased obviously (P<0.05). Both mRNA and protein expressions of E-cadherin were decreased significantly with prolonged hypoxia, while mRNA and protein expressions of CXCR4 increased significantly (P<0.05). After silencing HIF-1alpha gene, expression of E-cadherin protein was up regulated, but with down-regulated expression of CXCR4 protein, with a decrease significantly in adhesion rate or invasive cell number of CNE-1 cells (P<0.05). CONCLUSIONS: Hypoxia can increase HIF-1alpha protein expression in nasopharyngeal carcinoma cell line CNE-1. Silencing HIF-1alpha by RNA interference can reduce inhesion and invasion abilities of CNE-1 cells, which may be mediated by down regulating E-cadherin expression and up-regulating CXCR4 expression. PMID- 26887999 TI - [Age-related expression of plasma membrane Ca(2+) -ATPase isoform 2 in the cochleas of C57BL/6J mice]. AB - OBJECTIVE: To investigate the location and distribution of plasma membrane Ca2+ ATPase isoform 2(PMCA2) in the cochleas of C57BL/6J mice at various ages (4w, 14w, 22w, 45w), and to reveal the relationship of PMCA2 and age-related hearing loss (AHL). METHODS: The distribution of PMCA2 in the cochleas of C57BL/6J mice was detected by immunohistochemistry at various ages (4w, 14w, 22w, 45w). Real time polymerase chain reaction (Rt-PCR) was used to detect the level of PMCA2 mRNA in the cochleas of C57BL/6J mice at the ages of 4, 14, 22 and 45 weeks old respectively. Using SPSS17.0 software for statistical analysis. RESULTS: PMCA2 was mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 was also observed in spiral ligament. Hair cells missed and the number of spiral ganglion cells reduced with age. Expression of PMCA2 in the cochleas of C57BL/6J mice also showed age-related decreasing. The results of Rt-PCR demonstrated the expression of mRNA of gene (Atp2b2) at 14 weeks age was significantly less than 4 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 22 weeks age was significantly less than 14 week-old mice cochlears (P<0.05). The expression of mRNA of gene (Atp2b2) at 45 weeks age was significantly less than 14 week-old mice cochlears (P<0.01). CONCLUSIONS: PMCA2 is mainly located in the hear cells, stria vascularis, and spiral ganglion cells. Faint labeling of PMCA2 is also observed in spiral ligament. The expression of PMCA2 demonstrates an age-related decrease with age. The mRNA expression level of PMCA2 gene(Atp2b2) in the cochleas of C57BL/6J mice displayed an age-related decrease. PMCA2 transporters may play a critical role in maintaining the normal morphology of the inner ear and it may be related to AHL. PMID- 26888000 TI - [Pathological changes of upper and lower respiratory tissue in rats with chronic intermittent hypoxia]. AB - OBJECTIVE: To investigate the pathological changes of chronic intermittent hypoxia on upper and lower respiratory tissue in experimental rats. METHODS: A total of 40 female SD rats were divided into 2 groups. Twenty rats were fed in normal state (control group), and 20 rats were fed in hypoxia environment (hypoxia group). The pathological changes of upper and lower respiratory tissue were observed under optical microscope. RESULTS: Chronic intermittent hypoxia resulted in irreversible changes both at upper and lower respiratory tract in rats. The thickness of the lamina propria in soft palate was significantly increased in hypoxia group (125.85 +/- 6.34) um vs. (57.26 +/- 4.67) um (t=36.330, P<0.01). Lung pathological examination in hypoxia group showed pulmonary interval thickening (2.15 +/- 0.49) um vs. (0.45 +/- 0.12) um (t=14.132, P<0.01). CONCLUSIONS: This study confirmed that long-term hypoxia can lead to organization reconstruction in upper and lower respiratory tract in rats. In OSAHS patients, it is suggested that earlier intervention could alliviate the pathological changes in respiratory system. PMID- 26888001 TI - [The role of rigid bronchoscope in the diagnosis and treatment of plastic bronchitis]. AB - OBJECTIVE: To explore the role of rigid bronchoscope in the diagnosis and treatment of plastic bronchitis. METHODS: Various clinical parameters, the key points of operation and postoperative recovery were analyzed in 8 patients with plastic bronchitis treated in Department and ICU using retrospective analysis. RESULTS: All cases demonstrated bronchial lumen stenosis, mucous membrance coarse, congestion, edema in the affected side. 2 cases had follicular hyperplasia, 1 case had a few ooze after taking out the plastic type. All cases had endogenous foreign bodies, taking the shape of the bronchial tree or a funicular. Block shape and sites were as follows: right main bronchus 2 cases, superior lobe of right lung 1 case, right middle bronchial 1 case, left main bronchus 2 cases, 1 case with left lower lobe, right main bronchus and left lower lobe bronchus 1 case. The breath sounds of the affected side become more enhanced after operation, with the alliviation of dyspnea. All cases recovered after ICU treatment. The pathologic examination were all type I plastic bronchitis. CONCLUSIONS: Removement of the endogenous foreign body via rigid bronchoscopy is the effective method in the treatment of plastic bronchitis. Plastic bronchitis is a rapid-developing critical, urgent disease.In order to reduce the mortality, early diagnosis and timely surgery are necessary. PMID- 26888002 TI - [Application of special larynx polypus forceps for difficult laryngeal exposure in microlaryngosurgery]. PMID- 26888003 TI - [The comprehensive treatment of one case with pseudoaneurysms of the extracranial internal carotid artery]. PMID- 26888004 TI - [Geniculate ganglion meningioma: a case report]. PMID- 26888005 TI - [Clinical analysis of epithelial-myoepithelial carcinoma occurring in the hypopharynx]. PMID- 26888006 TI - [Alveolar soft part sarcoma of the head and neck: clinical and imaging features in two cases]. PMID- 26888007 TI - [Advance research of speech elicited auditory brainstem responses]. PMID- 26888008 TI - [MicroRNAs and allergic rhinitis]. PMID- 26888009 TI - [Advances in parathyroid carcinoma research]. PMID- 26888010 TI - Engineering the electronic and magnetic properties of d(0) 2D dichalcogenide materials through vacancy doping and lattice strains. AB - We have systematically investigated the effects of different vacancy defects in 2D d(0) materials SnS2 and ZrS2 using first principles calculations. The theoretical results show that the single cation vacancy and the vacancy complex like V-SnS6 can induce large magnetic moments (3-4 MUB) in these single layer materials. Other defects, such as V-SnS3, V-S, V-ZrS3 and V-ZrS6, can result in n type conductivity. In addition, the ab initio studies also reveal that the magnetic and conductive properties from the cation vacancy and the defect complex V-SnS6 can be modified using the compressive/tensile strain of the in-plane lattices. Specifically, the V-Zr doped ZrS2 monolayer can be tuned from a ferromagnetic semiconductor to a metallic/half-metallic material with decreasing/increasing magnetic moments depending on the external compressive/tensile strains. On the other hand, the semiconducting and magnetic properties of V-Sn doped SnS2 is preserved under different lattice compression and tension. For the defect complex like V-SnS6, only the lattice compression can tune the magnetic moments in SnS2. As a result, by manipulating the fabrication parameters, the magnetic and conductive properties of SnS2 and ZrS2 can be tuned without the need for chemical doping. PMID- 26888011 TI - Transdermal Delivery of siRNA through Microneedle Array. AB - Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively. PMID- 26888012 TI - Effect of free-breathing on left ventricular rotational mechanics in healthy subjects and patients with duchenne muscular dystrophy. AB - PURPOSE: Cardiovascular magnetic resonance imaging exams can be performed during free-breathing. This may be especially important for boys with Duchenne muscular dystrophy (DMD) given their frequently limited breath-hold abilities. The impact of the respiratory compensation method on quantitative measurements of left ventricular (LV) rotational mechanics is incompletely understood. The purpose of this study was to evaluate differences in LV rotational mechanics acquired during breath-holding (BH), free-breathing with averaging (AVG), and free-breathing with respiratory bellows gating (BEL). METHODS: LV short-axis tagged images from healthy subjects (N = 16) and DMD patients (N = 5) were acquired with BH, AVG, and BEL. LV twist and circumferential-longitudinal shear (CL-shear) angle were measured using the Fourier Analysis of STimulated echoes (FAST) method. RESULTS: Peak LV twist estimates using BEL were significantly lower compared with BH in both healthy subjects (10.2 +/- 3.6 degrees versus 12.9 +/- 2.3 degrees , P = 0.003) and patients with DMD (8.6 +/- 3.6 degrees versus 10.5 +/- 3.6 degrees , P = 0.004). AVG results were in between BEL and BH. No significant differences in CL-shear were detected between BEL and BH. CONCLUSION: Breath-holding directly affects estimates of peak LV twist, but not CL-shear. Using a free-breathing strategy for the evaluation of cardiac function is important for intrasubject longitudinal studies, intersubject comparisons, and multicenter trials for patients with DMD. Magn Reson Med 77:864-869, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26888013 TI - Reduced rate of sickle-related complications in Brazilian patients carrying HbF promoting alleles at the BCL11A and HMIP-2 loci. AB - The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke. PMID- 26888015 TI - Programmable DNA Hydrogels Assembled from Multidomain DNA Strands. AB - Hydrogels are important in biological and medical applications, such as drug delivery and tissue engineering. DNA hydrogels have attracted significant attention due to the programmability and biocompatibility of the material. We developed a series of low-cost one-strand DNA hydrogels self-assembled from single-stranded DNA monomers containing multiple palindromic domains. This new hydrogel design is simple and programmable. Thermal stability, mechanical properties, and loading capacity of these one-strand DNA hydrogels can be readily regulated by simply adjusting the DNA domains. PMID- 26888014 TI - Structure and biological function of ENPP6, a choline-specific glycerophosphodiester-phosphodiesterase. AB - Choline is an essential nutrient for all living cells and is produced extracellularly by sequential degradation of phosphatidylcholine (PC). However, little is known about how choline is produced extracellularly. Here, we report that ENPP6, a choline-specific phosphodiesterase, hydrolyzes glycerophosphocholine (GPC), a degradation product of PC, as a physiological substrate and participates in choline metabolism. ENPP6 is highly expressed in liver sinusoidal endothelial cells and developing oligodendrocytes, which actively incorporate choline and synthesize PC. ENPP6-deficient mice exhibited fatty liver and hypomyelination, well known choline-deficient phenotypes. The choline moiety of GPC was incorporated into PC in an ENPP6-dependent manner both in vivo and in vitro. The crystal structure of ENPP6 in complex with phosphocholine revealed that the choline moiety of the phosphocholine is recognized by a choline-binding pocket formed by conserved aromatic and acidic residues. The present study provides the molecular basis for ENPP6-mediated choline metabolism at atomic, cellular and tissue levels. PMID- 26888016 TI - Deposition Form and Bioaccessibility of Keto-carotenoids from Mamey Sapote (Pouteria sapota), Red Bell Pepper (Capsicum annuum), and Sockeye Salmon (Oncorhynchus nerka) Filet. AB - The ultrastructure and carotenoid-bearing structures of mamey sapote (Pouteria sapota) chromoplasts were elucidated using light and transmission electron microscopy and compared to carotenoid deposition forms in red bell pepper (Capsicum annuum) and sockeye salmon (Oncorhynchus nerka). Globular-tubular chromoplasts of sapote contained numerous lipid globules and tubules embodying unique provitamin A keto-carotenoids in a lipid-dissolved and presumably liquid crystalline form, respectively. Bioaccessibility of sapotexanthin and cryptocapsin was compared to that of structurally related keto-carotenoids from red bell pepper and salmon. Capsanthin from bell pepper was the most bioaccessible pigment, followed by sapotexanthin and cryptocapsin esters from mamey sapote. In contrast, astaxanthin from salmon was the least bioaccessible keto-carotenoid. Thermal treatment and fat addition consistently enhanced bioaccessibility, except for astaxanthin from naturally lipid-rich salmon, which remained unaffected. Although the provitamin A keto-carotenoids from sapote were highly bioaccessible, their qualitative and quantitative in vivo bioavailability and their conversion to vitamin A remains to be confirmed. PMID- 26888017 TI - Translating a health service intervention into a rural setting: lessons learned. AB - BACKGROUND: Limited research exists on the process of applying knowledge translation (KT) methodology to a rural-based population health intervention. METHODS: This study reports on the implementation and translational stages of a previously described Co-creating KT (Co-KT) framework in the rural town of Port Lincoln, South Australia (population: 14,000). The Co-KT framework involves five steps: (i) collecting local data; (ii) building stakeholder relationships; (iii) designing an evidence-based intervention incorporating local knowledge; (iv) implementation and evaluation of the intervention; and (v) translating the research into policy and practice. Barriers and enablers to the overall Co-KT implementation process were identified. Our intervention focused on musculoskeletal (MSK) conditions. RESULTS: Although the Co-KT framework was valuable in engaging with the community, translating the final intervention into daily clinical practice was prevented by a lack of an accessible policy or financial framework to anchor the appropriate intervention, a lack of continued engagement with stakeholders, access problems to general practitioners (GPs) and Allied Health Professionals; and the paucity of referrals from GPs to Allied Health Professionals. Consequently, while many aspects of the intervention were successful, including the improvement of both function and pain in study participants, the full implementation of the Co-KT framework was not possible. DISCUSSION: This study implemented and evaluated a Co-KT framework for a population with MSK conditions, linking locally generated health care system knowledge with academic input. Further policy, health system changes, and on-the ground support are needed to overcome the identified implementation challenges in order to create sustainable and effective system change. PMID- 26888018 TI - Is Leptospira able to survive in raw milk? Study on the inactivation at different storage times and temperatures. AB - The consumption of raw milk is currently increasing due to several beneficial aspects, such as nutritional qualities, taste, and health benefits. However, some authors highlight the potential risk associated with raw milk consumption. In Italy, while the absence of some pathogen microorganisms is set by the regional regulation DGR 381/2007, for other microorganisms, such as Leptospira, no recommendations are provided. Leptospira is not ascribed among classical milk pathogens; however, it can potentially be present in raw milk. The aim of this study was to evaluate the survival in raw milk of six serovars of Leptospira after storage at different temperatures (4 degrees C +/- 2 degrees C, 20 degrees C +/- 2 degrees C, and 30 degrees C +/- 2 degrees C) for different incubation times (20 min, 45 min, 1 h, and 1 h and 30 min), in order to determine the potential risk for consumers. Moreover, the immediate effect of bovine, goat, and donkey raw milk on tested Leptospira serovars was visually evaluated. After incubation, all samples were subcultured in EMJH and incubated aerobically at 30 degrees C for 3 months. All inoculated media were weekly examined by dark-field microscope in order to assess Leptospira survival. Extemporary observation of strains' behavior in milk allowed to detect an almost immediate motility loss, and no leptospires were detected by microscopic observations carried out weekly during the trial period. According to our results, it could be possible to exclude raw milk as a source of Leptospira infection for consumers. PMID- 26888019 TI - Contralateral tension pneumothorax during video-assisted thorascoscopic surgery for lung cancer: a case report. AB - Contralateral tension pneumothorax during one-lung ventilation is a rare but catastrophic surgical complication. A 72-year-old Japanese male with lung cancer underwent right upper lobectomy with video-assisted thoracoscopic surgery. Despite use of various methods for maintaining oxygenation during one-lung ventilation, percutaneous oxygen saturation was unstable from the start of surgery and suddenly decreased with a drop in blood pressure. An intraoperative chest X-ray revealed a tension pneumothorax of the dependent lung. Insertion of a chest drain saved the patient's life. This case suggests that a contralateral tension pneumothorax should be considered as a possible cause when adequate oxygenation cannot be maintained during one-lung ventilation. PMID- 26888020 TI - Bullying and Other Forms of Peer Victimization in Adolescence and Alcohol Use. AB - To examine the relationship between bullying and other forms of peer victimization in adolescence and alcohol use or misuse, all the pertinent studies were reviewed. Fourteen databases were searched. Blind assessments of study eligibility and quality were performed by two independent researchers. Seventy four studies including 2,066,131 participants across 56 countries all over the world and meeting minimum quality criteria that were enough to ensure objectivity and to not invalidate results were analyzed. Across studies, evidence for a significant association between peer victimization and alcohol use or misuse was conflicting. Results were affected by sample size, definition of victim status, specific forms of peer victimization, and specific types of alcohol consumption. There was some evidence for a number of mediating or moderating variables, such as depression, coping, drinking motives, attachment to school, social support, and gender. Findings are discussed according to stress-coping and self-medication hypotheses. Alternative etiological mechanisms are also considered. PMID- 26888021 TI - Long-term serial xenotransplantation of juvenile myelomonocytic leukemia recapitulates human disease in Rag2-/-gammac-/- mice. AB - Juvenile myelomonocytic leukemia is a clonal malignant disease affecting young children. Current cure rates, even with allogeneic hematopoietic stem cell transplantation, are no better than 50%-60%. Pre-clinical research on juvenile myelomonocytic leukemia is urgently needed for the identification of novel therapies but is hampered by the unavailability of culture systems. Here we report a xenotransplantation model that allows long-term in vivo propagation of primary juvenile myelomonocytic leukemia cells. Persistent engraftment of leukemic cells was achieved by intrahepatic injection of 1*10(6) cells into newborn Rag2(-/-)gammac(-/-) mice or intravenous injection of 5*10(6) cells into 5-week old mice. Key characteristics of juvenile myelomonocytic leukemia were reproduced, including cachexia and clonal expansion of myelomonocytic progenitor cells that infiltrated bone marrow, spleen, liver and, notably, lung. Xenografted leukemia cells led to reduced survival of recipient mice. The stem cell character of juvenile myelomonocytic leukemia was confirmed by successful serial transplantation that resulted in leukemia cell propagation for more than one year. Independence of exogenous cytokines, low donor cell number and slowly progressing leukemia are advantages of the model, which will serve as an important tool to research the pathophysiology of juvenile myelomonocytic leukemia and test novel pharmaceutical strategies such as DNA methyltransferase inhibition. PMID- 26888023 TI - Analysis of Mycobacterium avium subsp. paratuberculosis Mutant Libraries Reveals Loci-dependent Transposition Biases and Strategies to Novel Mutant Discovery. AB - Mycobacterium avium subsp. paratuberculosis (MAP), the etiologic agent of Johne's disease, is one of the most important bacterial pathogens in ruminants. A thorough understanding of MAP pathogenesis is needed to develop new vaccines and diagnostic tests. The generation of comprehensive random transposon mutant libraries is a fundamental genetic technology to determine the role of genes in physiology and pathogenesis. In this study, whole MAP genome analysis compared the insertion sites for the mycobacterial transposon Tn5367 derived from the Mycobacterium smegmatis insertion sequence IS1096 and the mariner transposon MycoMarT7 carrying the Himar1 transposase. We determined that only MycoMarT7 provides a random representation of insertions in 99% of all MAP genes. Analysis of the MAP K-10 genome indicated that 710 of all open reading frames do not possess IS1096 recognition sites, while only 37 do not have the recognition site for MycoMarT7. Thus, a significant number of MAP genes remain underrepresented in insertion libraries from IS1096 derived transposons. Analysis of MycomarT7 and Tn5367 mutants showed that Tn5367 has a predilection to insert within intergenic regions, suggesting that MycoMarT7 is more adequate to generate a comprehensive library. However, we uncovered the novel finding that both transposons have loci dependent biases with Tn5367 being the most skewed. These loci-dependent transposition biases lead to an underestimation of the number of independent mutants required to generate a comprehensive mutant library, leading to an overestimation of essential genes. Herein, we also demonstrated a useful platform for gene discovery and analysis by isolating three novel mutants for each transposon. PMID- 26888022 TI - Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. AB - The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of >=12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as >= 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836). PMID- 26888024 TI - The safety of incretin based drug treatments for type 2 diabetes. PMID- 26888025 TI - IVF results in patients with very low serum AMH are significantly affected by chronological age. AB - PURPOSE: The aims of this study were to assess the outcome of in vitro fertilization (IVF) in women with very low circulating anti-mullerian hormone (AMH) and to investigate factors affecting their probability of pregnancy. METHODS: The outcome of 448 IVF cycles in 361 women with circulating AMH <0.5 ng/ml was retrospectively analyzed. RESULTS: Cycle cancellation rate was 14.5 %; patients whose cycle was cancelled had significantly lower AMH than women who reached oocyte pickup (OPU). Among those who reached OPU, age significantly affected the success rate: despite comparable AMH levels, patients below 35 years obtained significantly more oocytes and a better clinical pregnancy rate (CPR)/OPU than patients aged 35-39 or 40-43 (31 % vs. 23.2 % vs. 10.2 %, respectively; p = 0.001). Differently, comparable IVF results were observed stratifying patients for AMH levels in the range 0.14-0.49 ng/ml. Multivariable logistic regression analysis confirmed that the probability of pregnancy was significantly affected by age, but not by small differences in AMH level. CONCLUSIONS: Women with very low (<0.5 ng/ml) AMH levels undergoing IVF still have reasonable chances of achieving a pregnancy, but their prognosis is significantly affected by chronological age. Very low AMH levels are associated with a relevant risk of cycle cancellation but should not be considered a reason to exclude a couple from IVF. PMID- 26888026 TI - Lidocaine for reducing propofol-induced pain on induction of anaesthesia in adults. AB - BACKGROUND: Pain on propofol injection is an untoward effect and this condition can reduce patient satisfaction. Intravenous lidocaine injection has been commonly used to attenuate pain on propofol injection. Although many studies have reported that lidocaine was effective in reducing the incidence and severity of pain, nevertheless, no systematic review focusing on lidocaine for preventing high-intensity pain has been published. OBJECTIVES: The objective of this review was to determine the efficacy and adverse effects of lidocaine in preventing high intensity pain on propofol injection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), Ovid MEDLINE (1950 To October 2014), Ovid EMBASE (1988 to October 2014), LILACS (1992 to October 2014) and searched reference lists of articles.We reran the search in November 2015. We found 11potential studies of interest, those studies were added to the list of 'Studies awaiting classification' and will be fully incorporated into the formal review findings when we update the review. SELECTION CRITERIA: We included randomized controlled trials (RCTs) using intravenous lidocaine injection as an intervention to decrease pain on propofol injection in adults. We excluded studies without a placebo or control group. DATA COLLECTION AND ANALYSIS: We collected selected studies with relevant criteria. We identified risk of bias in five domains according to the following criteria: random sequence generation, allocation concealment, adequacy of blinding, completeness of outcome data and selective reporting. We performed meta-analysis by direct comparisons of intervention versus control. We estimated the summary odds ratios (ORs) and 95% confidence intervals using the random-effects Mantel-Haenszel method in RevMan 5.3. We used the I(2) statistic to assess statistical heterogeneity. We assessed overall quality of evidence using the GRADE approach. MAIN RESULTS: We included 87 studies, 84 of which (10,460 participants) were eligible for quantitative analysis in the review. All participants, aged 13 years to 89 years, were American Society of Anesthesiologists (ASA) I-III patients undergoing elective surgery. Each study was conducted in a single centre in high- , middle- and low income countries worldwide. According to the risk of bias assessment, all except five studies were identified as being of satisfactory methodological quality, allowing 84 studies to be combined in the meta-analysis. Five of the 84 studies were assessed as high risk of bias: one for participant and personnel blinding, one for incomplete outcome data, and three for other potential sources of bias.The overall incidence of pain and high-intensity pain following propofol injection in the control group were 64% (95% CI 60% to 67.9%) and 38.1% (95% CI 33.4% to 43.1%), respectively while those in the lidocaine group were 30.2% (95% CI 26.7% to 33.7%) and 11.8% (95% CI 9.7% to 13.8%). Both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection (lidocaine admixture OR 0.19, 95% CI 0.15 to 0.25, 31 studies, 4927 participants, high quality evidence; lidocaine pretreatment OR 0.13, 95% CI 0.10 to 0.18, 43 RCTs, 4028 participants, high-quality evidence). Similarly, lidocaine administration could considerably decrease the incidence of pain when premixed with the propofol (OR 0.19, 95% CI 0.15 to 0.24, 36 studies, 5628 participants, high-quality evidence) or pretreated prior to propofol injection (OR 0.14, 95% CI 0.11 to 0.18, 52 studies, 4832 participants, high-quality evidence). Adverse effects of lidocaine administration were rare. Thrombophlebitis was reported in only two studies (OR not estimated, low-quality evidence). No studies reported patient satisfaction. AUTHORS' CONCLUSIONS: Overall, the quality of the evidence was high. Currently available data from RCTs are sufficient to confirm that both lidocaine admixture and pretreatment were effective in reducing pain on propofol injection. Furthermore, there were no significant differences of effect between the two techniques. PMID- 26888027 TI - Carbon-Coated Hierarchical SnO2 Hollow Spheres for Lithium Ion Batteries. AB - Hierarchical SnO2 hollow spheres self-assembled from nanosheets were prepared with and without carbon coating. The combination of nanosized architecture, hollow structure, and a conductive carbon layer endows the SnO2 -based anode with improved specific capacity and cycling stability, making it more promising for use in lithium ion batteries. PMID- 26888028 TI - Oxygen-induced social behaviours in Pristionchus pacificus have a distinct evolutionary history and genetic regulation from Caenorhabditis elegans. AB - Wild isolates of the nematode Caenorhabditis elegans perform social behaviours, namely clumping and bordering, to avoid hyperoxia under laboratory conditions. In contrast, the laboratory reference strain N2 has acquired a solitary behaviour in the laboratory, related to a gain-of-function variant in the neuropeptide Y-like receptor NPR-1. Here, we study the evolution and natural variation of clumping and bordering behaviours in Pristionchus pacificus nematodes in a natural context, using strains collected from 22 to 2400 metres above sea level on La Reunion Island. Through the analysis of 106 wild isolates, we show that the majority of strains display a solitary behaviour similar to C. elegans N2, whereas social behaviours are predominantly seen in strains that inhabit high altitude locations. We show experimentally that P. pacificus social strains perform clumping and bordering to avoid hyperoxic conditions in the laboratory, suggesting that social strains may have adapted to or evolved a preference for the lower relative oxygen levels available at high altitude in nature. In contrast to C. elegans, clumping and bordering in P. pacificus do not correlate with locomotive behaviours in response to changes in oxygen conditions. Furthermore, QTL analysis indicates clumping and bordering to represent complex quantitative traits. Thus, clumping and bordering behaviours represent an example of phenotypic convergence with a different evolutionary history and distinct genetic control in both nematode species. PMID- 26888030 TI - Predator-guided sampling reveals biotic structure in the bathypelagic. AB - We targeted a habitat used differentially by deep-diving, air-breathing predators to empirically sample their prey's distributions off southern California. Fine scale measurements of the spatial variability of potential prey animals from the surface to 1,200 m were obtained using conventional fisheries echosounders aboard a surface ship and uniquely integrated into a deep-diving autonomous vehicle. Significant spatial variability in the size, composition, total biomass, and spatial organization of biota was evident over all spatial scales examined and was consistent with the general distribution patterns of foraging Cuvier's beaked whales (Ziphius cavirostris) observed in separate studies. Striking differences found in prey characteristics between regions at depth, however, did not reflect differences observed in surface layers. These differences in deep pelagic structure horizontally and relative to surface structure, absent clear physical differences, change our long-held views of this habitat as uniform. The revelation that animals deep in the water column are so spatially heterogeneous at scales from 10 m to 50 km critically affects our understanding of the processes driving predator-prey interactions, energy transfer, biogeochemical cycling, and other ecological processes in the deep sea, and the connections between the productive surface mixed layer and the deep-water column. PMID- 26888029 TI - Support for the evolutionary speed hypothesis from intraspecific population genetic data in the non-biting midge Chironomus riparius. AB - The evolutionary speed hypothesis (ESH) proposes a causal mechanism for the latitudinal diversity gradient. The central idea of the ESH is that warmer temperatures lead to shorter generation times and increased mutation rates. On an absolute time scale, both should lead to an acceleration of selection and drift. Based on the ESH, we developed predictions regarding the distribution of intraspecific genetic diversity: populations of ectothermic species with more generations per year owing to warmer ambient temperatures should be more differentiated from each other, accumulate more mutations and show evidence for increased mutation rates compared with populations in colder regions. We used the multivoltine insect species Chironomus riparius to test these predictions with cytochrome oxidase I (COI) sequence data and found that populations from warmer regions are indeed significantly more differentiated and have significantly more derived haplotypes than populations from colder regions. We also found a significant correlation of the annual mean temperature with the population mutation parameter theta that serves as a proxy for the per generation mutation rate under certain assumptions. This pattern could be corroborated with two nuclear loci. Overall, our results support the ESH and indicate that the thermal regime experienced may be crucially driving the evolution of ectotherms and may thus ultimately govern their speciation rate. PMID- 26888031 TI - Information use and resource competition: an integrative framework. AB - Organisms may reduce uncertainty regarding how best to exploit their environment by collecting information about resource distribution. We develop a model to demonstrate how competition can facilitate or constrain an individual's ability to use information when acquiring resources. As resource distribution underpins both selection on information use and the strength and nature of competition between individuals, we demonstrate interdependencies between the two that should be common in nature. Individuals in our model can search for resources either personally or by using social information. We explore selection on social information use across a comprehensive range of ecological conditions, generalizing the producer-scrounger framework to a wide diversity of taxa and resources. We show that resource ecology--defined by scarcity, depletion rate and monopolizability--determines patterns of individual differences in social information use. These differences suggest coevolutionary processes linking dominance systems and social information use, with implications for the evolutionary demography of populations. PMID- 26888032 TI - Regime shifts in marine communities: a complex systems perspective on food web dynamics. AB - Species composition and habitats are changing at unprecedented rates in the world's oceans, potentially causing entire food webs to shift to structurally and functionally different regimes. Despite the severity of these regime shifts, elucidating the precise nature of their underlying processes has remained difficult. We address this challenge with a new analytic approach to detect and assess the relative strength of different driving processes in food webs. Our study draws on complexity theory, and integrates the network-centric exponential random graph modelling (ERGM) framework developed within the social sciences with community ecology. In contrast to previous research, this approach makes clear assumptions of direction of causality and accommodates a dynamic perspective on the emergence of food webs. We apply our approach to analysing food webs of the Baltic Sea before and after a previously reported regime shift. Our results show that the dominant food web processes have remained largely the same, although we detect changes in their magnitudes. The results indicate that the reported regime shift may not be a system-wide shift, but instead involve a limited number of species. Our study emphasizes the importance of community-wide analysis on marine regime shifts and introduces a novel approach to examine food webs. PMID- 26888033 TI - Trophic complexity in aqueous systems: bacterial species richness and protistan predation regulate dissolved organic carbon and dissolved total nitrogen removal. AB - Loading of water bodies with dissolved organic carbon (DOC) and dissolved total nitrogen (DTN) affects their integrity and functioning. Microbial interactions mitigate the negative effects of high nutrient loads in these ecosystems. Despite numerous studies on how biodiversity mediates ecosystem functions, whether and how diversity and complexity of microbial food webs (horizontal, vertical) and the underlying ecological mechanisms influence nutrient removal has barely been investigated. Using microbial microcosms accommodating systematic combinations of prey (bacteria) and predator (protists) species, we showed that increasing bacterial richness improved the extent and reliability of DOC and DTN removal. Bacterial diversity drove nutrient removal either due to species foraging physiology or functional redundancy, whereas protistan diversity affected nutrient removal through bacterial prey resource partitioning and changing nutrient balance in the system. Our results demonstrate that prey-predator diversity and trophic interactions interactively determine nutrient contents, thus implying the vital role of microbial trophic complexity as a biological buffer against DOC and DTN. PMID- 26888034 TI - Brain size is correlated with endangerment status in mammals. AB - Increases in relative encephalization (RE), brain size after controlling for body size, comes at a great metabolic cost and is correlated with a host of cognitive traits, from the ability to count objects to higher rates of innovation. Despite many studies examining the implications and trade-offs accompanying increased RE, the relationship between mammalian extinction risk and RE is unknown. I examine whether mammals with larger levels of RE are more or less likely to be at risk of endangerment than less-encephalized species. I find that extant species with large levels of encephalization are at greater risk of endangerment, with this effect being strongest in species with small body sizes. These results suggest that RE could be a valuable asset in estimating extinction vulnerability. Additionally, these findings suggest that the cost-benefit trade-off of RE is different in large-bodied species when compared with small-bodied species. PMID- 26888035 TI - Multiple evolutionary origins of Australian soil-burrowing cockroaches driven by climate change in the Neogene. AB - Parallel evolution is the independent appearance of similar derived phenotypes from similar ancestral forms. It is of key importance in the debate over whether evolution is stochastic and unpredictable, or subject to constraints that limit available phenotypic options. Nevertheless, its occurrence has rarely been demonstrated above the species level. Climate change on the Australian landmass over the last approximately 20 Myr has provided conditions conducive to parallel evolution, as taxa at the edges of shrinking mesic habitats adapted to drier biomes. Here, we investigate the phylogeny and evolution of Australian soil burrowing and wood-feeding blaberid cockroaches. Soil burrowers (subfamily Geoscapheinae) are found in relatively dry sclerophyllous and scrubland habits, whereas wood feeders (subfamily Panesthiinae) are found in rainforest and wet sclerophyll. We sequenced and analysed mitochondrial and nuclear markers from 142 specimens, and estimated the evolutionary time scale of the two subfamilies. We found evidence for the parallel evolution of soil-burrowing taxa from wood feeding ancestors on up to nine occasions. These transitions appear to have been driven by periods of aridification during the Miocene and Pliocene across eastern Australia. Our results provide an illuminating example of climate-driven parallel evolution among species. PMID- 26888036 TI - Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length. AB - Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNgamma), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNgamma responses are selectively lost from this population. IFNgamma responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNgamma response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNgamma response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them. PMID- 26888037 TI - Opposing phylogenetic diversity gradients of plant and soil bacterial communities. AB - Plants and soil microbes show parallel patterns of species-level diversity. Diverse plant communities release a wider range of organics that are consumed by more microbial species. We speculated, however, that diversity metrics accounting for the evolutionary distance across community members would reveal opposing patterns between plant and soil bacterial phylogenetic diversity. Plant phylogenetic diversity enhances plant productivity and thus expectedly soil fertility. This, in turn, might reduce bacterial phylogenetic diversity by favouring one (or a few) competitive bacterial clade. We collected topsoils in 15 semi-arid plant patches and adjacent low-cover areas configuring a plant phylodiversity gradient, pyrosequenced the 16S rRNA gene to identify bacterial taxa and analysed soil fertility parameters. Structural equation modelling showed positive effects of both plant richness and phylogenetic diversity on soil fertility. Fertility increased bacterial richness but reduced bacterial phylogenetic diversity. This might be attributed to the competitive dominance of a lineage based on its high relative fitness. This suggests biotic interactions as determinants of the soil bacterial community assembly, while emphasizing the need to use phylogeny-informed metrics to tease apart the processes underlying the patterns of diversity. PMID- 26888038 TI - CFTR channel in oocytes from Xenopus laevis and its regulation by xShroom1 protein. AB - Shroom is a family of related proteins linked to the actin cytoskeleton. xShroom1 is constitutively expressed in Xenopus laevis oocytes, and it is required for the expression of the epithelial sodium channel (ENaC). As there is a close relationship between ENaC and the cystic fibrosis transmembrane regulator (CFTR), we examined the action of xShroom1 on CFTR expression and activity. Biotinylation was used to measure CFTR surface expression, and currents were registered with voltage clamp when stimulated with forskolin and 3-isobutyl-1-methylxanthine. Oocytes were coinjected with CFTR complementary RNAs (cRNAs) and xShroom1 sense or antisense oligonucleotides. We observed an increment in CFTR currents and CFTR surface expression in oocytes coinjected with CFTR and xShroom1 antisense oligonucleotides. MG-132, a proteasome inhibitor, did not prevent the increment in currents when xShroom1 was suppressed by antisense oligonucleotides. In addition, we inhibited the delivery of newly synthesized proteins to the plasma membrane with BFA and we found that the half-life of plasma membrane CFTR was prolonged when coinjected with the xShroom1 antisense oligonucleotides. Chloroquine, an inhibitor of the late endosome/lysosome, did not significantly increase CFTR currents when xShroom1 expression was inhibited. The higher expression of CFTR when xShroom1 is suppressed is in concordance with the functional studies suggesting that the suppression of the xShroom1 protein resulted in an increment in CFTR currents by promoting the increase of the half life of CFTR in the plasma membrane. The role of xShroom1 in regulating CFTR expression could be relevant in the understanding of the channel malfunction in several diseases. PMID- 26888039 TI - Nano-Fenton Reactors as a New Class of Oxidative Stress Amplifying Anticancer Therapeutic Agents. AB - Cancer cells, compared to normal cells, are under oxidative stress associated with an elevated level of reactive oxygen species (ROS) and are more vulnerable to oxidative stress induced by ROS generating agents. Thus, manipulation of the ROS level provides a logical approach to kill cancer cells preferentially, without significant toxicity to normal cells, and great efforts have been dedicated to the development of strategies to induce cytotoxic oxidative stress for cancer treatment. Fenton reaction is an important biological reaction in which irons convert hydrogen peroxide (H2O2) to highly toxic hydroxyl radicals that escalate ROS stress. Here, we report Fenton reaction-performing polymer (PolyCAFe) micelles as a new class of ROS-manipulating anticancer therapeutic agents. Amphiphilic PolyCAFe incorporates H2O2-generating benzoyloxycinnamaldehyde and iron-containing compounds in its backbone and self assembles to form micelles that serve as Nano-Fenton reactors to generate cytotoxic hydroxyl radicals, killing cancer cells preferentially. When intravenously injected, PolyCAFe micelles could accumulate in tumors preferentially to remarkably suppress tumor growth, without toxicity to normal tissues. This study demonstrates the tremendous translatable potential of Nano Fenton reactors as a new class of anticancer drugs. PMID- 26888040 TI - Collective chemotaxis and segregation of active bacterial colonies. AB - Still recently, bacterial fluid suspensions have motivated a lot of works, both experimental and theoretical, with the objective to understand their collective dynamics from universal and simple rules. Since some species are active, most of these works concern the strong interactions that these bacteria exert on a forced flow leading to instabilities, chaos and turbulence. Here, we investigate the self-organization of expanding bacterial colonies under chemotaxis, proliferation and eventually active-reaction. We propose a simple model to understand and quantify the physical properties of these living organisms which either give cohesion or on the contrary dispersion to the colony. Taking into account the diffusion and capture of morphogens complicates the model since it induces a bacterial density gradient coupled to bacterial density fluctuations and dynamics. Nevertheless under some specific conditions, it is possible to investigate the pattern formation as a usual viscous fingering instability. This explains the similarity and differences of patterns according to the physical bacterial suspension properties and explain the factors which favor compactness or branching. PMID- 26888041 TI - Development and regulation of exosome-based therapy products. AB - Recently, various innovative therapies involving the ex vivo manipulation and subsequent reintroduction of exosome-based therapeutics into humans have been developed and validated, although no exosome-based therapeutics have yet to be brought into the clinic. Exosomes are nanosized vesicles secreted by many cells that utilize them for cell-to-cell communications to facilitate transport of proteins and genetic material. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes offer distinct advantages that exceptionally position them as highly effective drug carriers. Additionally, exosomes can exert unique biological activity reflective of their origin that may be used for therapy of various diseases. In fact, exosomes have benefits of both synthetic nanocarriers and cell-mediated drug delivery systems, and avoid their limitations. This concise review highlights the recent developments in exosome based drug delivery systems and the main regulatory considerations for using this type of therapeutic in clinic. WIREs Nanomed Nanobiotechnol 2016, 8:744-757. doi: 10.1002/wnan.1395 For further resources related to this article, please visit the WIREs website. PMID- 26888042 TI - Photodynamic Therapy for Malignant Brain Tumors. AB - Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area. PMID- 26888044 TI - Odontogenic myxoma involving the orbit in a 3-year-old boy: removal, reconstruction and review of the literature. AB - We present a rare case of a 3-year-old boy with an odontogenic myxoma (OM) involving the orbita. Including our case, only nine cases of OM have been reported to involve the eye in children.There is no gold standard for treatment of OM in children with orbital involvement. The recurrence rate of OM in children seems low, which advocates for less invasive surgery. A gentle resection of the OM was carried out. The floor and medial wall of the orbit was reconstructed immediately using a non-resorbable Medpor implant with passive adaptation. Reconstruction with a Medpor implant in children has rarely been reported in the literature. No clinical or radiological recurrence was observed 24 months after surgical removal, and the patient presented with symmetric appearance and normal vision. PMID- 26888045 TI - Endoscopic resection of invasive glomangiopericytoma following preoperative embolisation. AB - We present a case of a 60-year-old woman with a 2-year history of nasal obstruction and unilateral recurrent epistaxis. Anterior rhinoscopy identified a unilateral hypervascular lobular mass occupying the entire left nasal cavity. Imaging studies documented an extensive soft tissue density lesion in the left nasal cavity with complete infiltration of the anterior ethmoid, limited indentation of the medial wall of the orbit, bone demineralisation of the cribriform plate and involvement of the anterior cranial fossa. The diagnosis of locally invasive glomangiopericytoma was obtained preoperatively through biopsy of the lesion, which resulted in a self-limited epistaxis that was easily controlled by nasal packing, confirming the vascular nature of the lesion. We discuss the diagnostic work up, imaging and surgical approach of this tumour, and review the recent literature on endoscopic treatment of these lesions. PMID- 26888043 TI - History of Neural Stem Cell Research and Its Clinical Application. AB - "Once development was ended...in the adult centers, the nerve paths are something fixed and immutable. Everything may die, nothing may be regenerated," wrote Santiago Ramon y Cajal, a Spanish neuroanatomist and Nobel Prize winner and the father of modern neuroscience. This statement was the central dogma in neuroscience for a long time. However, in the 1960s, neural stem cells (NSCs) were discovered. Since then, our knowledge about NSCs has continued to grow. This review focuses on our current knowledge about NSCs and their surrounding microenvironment. In addition, the clinical application of NSCs for the treatment of various central nervous system diseases is also summarized. PMID- 26888046 TI - Correlates of dietary energy misreporting among European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. AB - This study examined the correlates of dietary energy under-reporting (UR) and over-reporting (OV) in European adolescents. Two self-administered computerised 24-h dietary recalls and physical activity data using accelerometry were collected from 1512 adolescents aged 12.5-17.5 years from eight European countries. Objective measurements of height and weight were obtained. BMI was categorised according to Cole/International Obesity Task Force (IOTF) cut-off points. Diet-related attitudes were assessed via self-administered questionnaires. Reported energy intake (EI) was compared with predicted total energy expenditure to identify UR and OV using individual physical activity objective measures. Associations between misreporting and covariates were examined by multilevel logistic regression analyses. Among all, 33.3 % of the adolescents were UR and 15.6 % were OV when considering mean EI. Overweight (OR 3.25; 95 % CI 2.01, 5.27) and obese (OR 4.31; 95 % CI 1.92, 9.65) adolescents had higher odds for UR, whereas underweight individuals were more likely to over report (OR 1.67; 95 % CI 1.01, 2.76). Being content with their own figures (OR 0.61; 95 % CI 0.41, 0.89) decreased the odds for UR, whereas frequently skipping breakfast (OR 2.14; 95 % CI 1.53, 2.99) was linked with higher odds for UR. Those being worried about gaining weight (OR 0.55; 95 % CI 0.33, 0.92) were less likely to OV. Weight status and psychosocial weight-related factors were found to be the major correlates of misreporting. Misreporting may reflect socially desirable answers and low ability to report own dietary intakes, but also may reflect real under-eating in an attempt to lose weight or real over-eating to reflect higher intakes due to growth spurts. Factors influencing misreporting should be identified in youths to clarify or better understand diet-disease associations. PMID- 26888047 TI - Comparative phylogeography of two monogenean species (Mazocraeidae) on the host of chub mackerel, Scomber japonicus, along the coast of China. AB - In the present paper, the phylogeographies of two monogenean species, Pseudokuhnia minor and Kuhnia scombri, on the same species of host, Scomber japonicus, were studied. Fragments of the mitochondrial cytochrome c oxidase subunit 1 gene were sequenced for 264 individuals of P. minor and 224 individuals of K. scombri collected from 10 localities along the coast of China. Genetic diversity of K. scombri was higher than that of P. minor, which may imply that P. minor has a lower evolution rate and/or is a younger species. The neighbour joining (NJ) trees of both parasites were comprised of two clades without association to sample sites, which is the signature of remixing populations following past division. Analyses of molecular variance and pairwise fixation index revealed different genetic structures for the populations of these two closely related species along the coast of China: P. minor without significant genetic structure, while K. scombri has some genetic differentiation. Both neutrality tests and mismatch distribution suggested that the populations of these two species of parasites experienced population expansion in the late Pleistocene era due to the glacial-interglacial cycles induced by climatic oscillations. PMID- 26888048 TI - The rare Costello variant HRAS c.173C>T (p.T58I) with severe neonatal hypertrophic cardiomyopathy. AB - We report a 10-year-old girl presenting with severe neonatal hypertrophic cardiomyopathy (HCM), feeding difficulties, mildly abnormal facial features, and progressive skeletal muscle symptoms but with normal cognitive development. Targeted oligonucleotide-selective sequencing of 101 cardiomyopathy genes revealed the genetic diagnosis, and the mutation was verified by Sanger sequencing in the patient and her parents. To offer insights into the potential mechanism of patient mutation, protein structural analysis was performed using the resolved structure of human activated HRAS protein with bound GTP analogue (PDB id 5P21) in Discovery Studio 4.5 (Dassault Systemes Biovia, San Diego, CA). The patient with hypertrophic cardiomyopathy and normal cognitive development was diagnosed with an HRAS mutation c.173C>T (p.T58I), a milder variant of Costello syndrome affecting a highly conserved amino acid, threonine 58. Our analysis suggests that the p.G12 mutations slow GTP hydrolysis rendering HRAS unresponsive to GTPase activating proteins, and resulting in permanently active state. The p.T58I mutation likely affects binding of guanidine-nucleotide-exchange factors, thereby promoting the active state but also allowing for slow inactivation. Patients with the HRAS mutation c.173C>T (p.T58I) might go undiagnosed because of the milder phenotype compared with other mutations causing Costello syndrome. We expand the clinical and molecular picture of the rare HRAS mutation by reporting the first case in Europe and the fourth case in the literature. Our protein structure analysis offers insights into the mechanism of the mildly activating p.T58I mutation. (c) 2016 Wiley Periodicals, Inc. PMID- 26888050 TI - Pred-binding: large-scale protein-ligand binding affinity prediction. AB - Drug target interactions (DTIs) are crucial in pharmacology and drug discovery. Presently, experimental determination of compound-protein interactions remains challenging because of funding investment and difficulties of purifying proteins. In this study, we proposed two in silico models based on support vector machine (SVM) and random forest (RF), using 1589 molecular descriptors and 1080 protein descriptors in 9948 ligand-protein pairs to predict DTIs that were quantified by Ki values. The cross-validation coefficient of determination of 0.6079 for SVM and 0.6267 for RF were obtained, respectively. In addition, the two-dimensional (2D) autocorrelation, topological charge indices and three-dimensional (3D)-MoRSE descriptors of compounds, the autocorrelation descriptors and the amphiphilic pseudo-amino acid composition of protein are found most important for Ki predictions. These models provide a new opportunity for the prediction of ligand receptor interactions that will facilitate the target discovery and toxicity evaluation in drug development. PMID- 26888051 TI - Categories of Large Numbers in Line Estimation. AB - How do people stretch their understanding of magnitude from the experiential range to the very large quantities and ranges important in science, geopolitics, and mathematics? This paper empirically evaluates how and whether people make use of numerical categories when estimating relative magnitudes of numbers across many orders of magnitude. We hypothesize that people use scale words-thousand, million, billion-to carve the large number line into categories, stretching linear responses across items within each category. If so, discontinuities in position and response time are expected near the boundaries between categories. In contrast to previous work (Landy, Silbert, & Goldin, 2013) that suggested only that a minority of college undergraduates employed categorical boundaries, we find that discontinuities near category boundaries occur in most or all participants, but that accurate and inaccurate participants respond in opposite ways to category boundaries. Accurate participants highlight contrasts within a category, whereas inaccurate participants adjust their responses toward category centers. PMID- 26888052 TI - l-carnitine protects rat hepatocytes from oxidative stress induced by T-2 toxin. AB - CONTEXT: Oxidative stress and mitochondrial dysfunction are thought to be the main mechanism of T-2 toxin toxicity. T-2 toxin is the most potent trichothecene mycotoxin which is present in agricultural products. L-carnitine, besides its anti-oxidative properties, facilitates the transportation of long-chain fatty acids in to mitochondrial matrix. OBJECTIVE: In this study we tested whether L carnitine, an antioxidant and a facilitator for long-chain fatty acid transportation across mitochondrial membranes, could protect rat hepatocytes against toxicity induced by T-2 toxin. MATERIALS AND METHODS: L-carnitine in low and high doses (50 and 500 mg/kg) was administered for five consecutive days to male Wistar rats. Hepatocytes were isolated and freshly exposed to appropriate concentration of T-2 toxin for 2 h followed by oxidative stress and cell death evaluations. RESULTS: Glutathione depletion, ROS overproduction and mitochondrial membrane potential collapse were determined under T-2 toxin exposure. Pretreatment with L-carnitine particularly at high-dose reduced toxicity and prevented the hepatocytes from abnormal caspase-3 activity and apoptosis. CONCLUSION: Low toxicity of L-carnitine and its mitochondrial protective effects promises an effective way to reduce or prevent the toxicity induced by certain environmental pollutants, including T-2 toxin. PMID- 26888053 TI - Ionic liquid electrolytes for reversible magnesium electrochemistry. AB - Mg has great potential as the basis for a safe, low cost energy storage technology, however, cycling of magnesium is difficult to achieve in most electrolytes. We demonstrate cycling of Mg from a novel alkoxyammonium ionic liquid. DFT calculations highlight the role that Mg coordination with [BH4](-) ions plays in the mechanism. PMID- 26888054 TI - Antagonistic activity of endo-beta-1,3-glucanase from a novel isolate, Streptomyces sp. 9X166, against black rot in orchids. AB - A total of 123 actinomycetes was isolated from 12 varieties of wild orchids and screened for potential antagonistic activity against Phytophthora, which causes black rot disease in orchids. In vitro and in vivo experimental results revealed that Streptomyces sp. strain 9X166 showed the highest antagonistic activity; its beta-1,3-glucanase production ability was a key mechanism for growth inhibition of the pathogen. PCR amplification and DNA sequencing of the 16S ribosomal RNA gene allowed the identification of this strain, with high similarity (99.93%) to the novel species Streptomyces similaensis. The glucanase enzyme, purified to homogeneity by anion exchange and gel filtration chromatography, showed a specific activity of 58 U mg(-1) (a 3.9-fold increase) and yield of 6.4%. The molecular weight, as determined by SDS-PAGE and gel filtration, was approximately 99 and 80 kDa, respectively, suggesting that the enzyme was a monomer. The purified enzyme showed the highest substrate specificity to laminarin, indicating that it was beta-1,3-glucanase. The hydrolyzed products of cello-oligosaccharides suggested that this enzyme was endo-type beta-1,3-glucanase. Streptomyces sp. 9X166 culture filtrate, possessing beta-1,3-glucanase activity, could degrade both freeze-dried and living mycelium. This is the first report on a beta-1,3 glucanase-producing Streptomyces sp. that could be an effective biocontrol agent for black rot disease in orchids. PMID- 26888055 TI - Understanding the Pathogenicity of Noncoding Mismatch Repair Gene Promoter Variants in Lynch Syndrome. AB - Lynch syndrome is the most common familial cancer condition that mainly predisposes to tumors of the colon and endometrium. Cancer susceptibility is caused by the autosomal dominant inheritance of a loss-of-function mutation or epimutation in one of the DNA mismatch repair (MMR) genes. Cancer risk assessment is often possible with nonsynonymous coding region mutations, but in many cases patients present with DNA sequence changes within noncoding regions, including the promoters, of MMR genes. The pathogenic role of promoter variants, and hence clinical significance, is unclear and this hinders the clinical management of carriers. In this review, we provide an overview of the classification of MMR gene variants, outline the laboratory assays and online resources that can be used to assess the causality of promoter variants in Lynch syndrome, and highlight some of the practical challenges of demonstrating the pathogenicity of these variants. In conclusion, we propose a guide that could be integrated into the current InSiGHT classification scheme to help determine if a MMR gene promoter variant is pathogenic. PMID- 26888058 TI - Digit-only sauropod pes trackways from China--evidence of swimming or a preservational phenomenon? AB - For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all. PMID- 26888056 TI - Blockade of Nicotine and Cannabinoid Reinforcement and Relapse by a Cannabinoid CB1-Receptor Neutral Antagonist AM4113 and Inverse Agonist Rimonabant in Squirrel Monkeys. AB - Nicotine, the main psychoactive component of tobacco, and (-)-Delta(9) tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, play major roles in tobacco and marijuana dependence as reinforcers of drug-seeking and drug-taking behavior. Drugs that act as inverse agonists of cannabinoid CB1 receptors in the brain can attenuate the rewarding and abuse-related effects of nicotine and THC, but their clinical use is hindered by potentially serious side effects. The recently developed CB1-receptor neutral antagonists may provide an alternative therapeutic approach to nicotine and cannabinoid dependence. Here we compare attenuation of nicotine and THC reinforcement and reinstatement in squirrel monkeys by the CB1-receptor inverse agonist rimonabant and by the recently developed CB1-receptor neutral antagonist AM4113. Both rimonabant and AM4113 reduced two effects of nicotine and THC that play major roles in tobacco and marijuana dependence: (1) maintenance of high rates of drug-taking behavior, and (2) priming- or cue-induced reinstatement of drug-seeking behavior in abstinent subjects (models of relapse). In contrast, neither rimonabant nor AM4113 modified cocaine-reinforced or food-reinforced operant behavior under similar experimental conditions. However, both rimonabant and AM4113 reduced cue induced reinstatement in monkeys trained to self-administer cocaine, suggesting the involvement of a common cannabinoid-mediated mechanism in the cue-induced reinstatement for different drugs of abuse. These findings point to CB1-receptor neutral antagonists as a new class of medications for treatment of both tobacco dependence and cannabis dependence. PMID- 26888057 TI - Reduced Inhibitory Control Mediates the Relationship Between Cortical Thickness in the Right Superior Frontal Gyrus and Body Mass Index. AB - Unhealthy eating behaviors often develop in the setting of inadequate inhibitory control, a function broadly ascribed to the prefrontal cortex (PFC). Regulation of inhibitory control by the PFC and its anatomical components and their contribution to increasing body mass index (BMI) are poorly understood. To study the role of PFC in the regulation of inhibitory control and body weight, we examined measures of cortical thickness in PFC sub-regions, inhibitory control (color-word interference task (CWIT)), and BMI in 91 healthy volunteers. We tested the predictive effect of PFC sub-regional cortical thickness on BMI and mediation by inhibitory control measured with CWIT. Measures of depression (BDI II), anxiety (STAI-T) and trauma-related symptoms (TSC-40) were collected; the disinhibition scale of the three-factor eating questionnaire (TFEQ) was used to assess disinhibited eating. We then tested the relationship between BD-II, STAI T, TSC-40, TFEQ, CWIT, and BMI with correlation analyses. Right superior frontal gyrus cortical thickness significantly predicted BMI (beta=-0.91; t=-3.2; p=0.002). Mediation analysis showed a significant indirect effect of cortical thickness on BMI mediated by inhibitory control (95% CI=-6.1, -0.67). BMI was unrelated to BDI-II, STAI-T, TSC-40, or TFEQ scores. We found an inverse relationship between cortical thickness in the right-superior frontal gyrus and BMI, which was fully mediated by inhibitory control neurocognitive performance. Our results suggest possible targets for neuromodulation in obesity (ie superior frontal gyrus) and a quantifiable mediator of their effects (ie inhibitory control). PMID- 26888059 TI - Reexamining the Association Between Positive Surgical Margins and Survival After Partial Nephrectomy in a Large American Cohort. AB - PURPOSE: To investigate the impact of positive surgical margins (PSM) on overall survival (OS) in a large American cohort with intermediate-term follow-up. PATIENTS AND METHODS: Using the National Cancer Data Base, we identified 6038 cases of pathological T1-T3a, nonmetastatic renal-cell carcinoma managed with partial nephrectomy (PN) from 2003 to 2006. Patients were stratified into two groups based on margin status. Predictors of positive margins were evaluated using multivariable logistic regression analysis. OS by margin status was evaluated using Kaplan-Meier analysis and the log-rank test. A multivariable Cox proportional hazards model was used to evaluate the adjusted association between margin status and survival. RESULTS: Overall, 302 (5.3%) patients had positive margins. On multivariable analysis, higher pathological T stage and higher comorbidity score were the only factors significantly associated with positive margins (p < 0.001 and p = 0.015, respectively). At 71-month median follow-up, the unadjusted 5-year OS for the entire cohort was 92%. Positive margins were significantly associated with decreased 5-year OS (89% vs 92%, p = 0.002), and this association remained significant in healthy patients (p = 0.027). On multivariable survival analysis, positive margins significantly predicted hastened time to all-cause death (hazards ratio 1.34; 95% CI 1.01, 1.78; p = 0.038). CONCLUSION: In the largest observational study to date, PSM were associated with worse OS after PN. Further study on cancer-specific outcomes with long-term follow-up is needed. PMID- 26888062 TI - Toxic effects of mercury on the cell nucleus of Dictyostelium discoideum. AB - Governmental agencies (www.epa.gov/mercury) and the scientific community have reported on the high toxicity due to mercury. Indeed, exposure to mercury can cause severe injury to the central nervous system and kidney in humans. Beyond its recognized toxicity, little is known regarding the molecular mechanisms involved in the actions of this heavy metal. Mercury has been also observed to form insoluble fibrous protein aggregates in the cell nucleus. We used D. discoideum to evaluate micronuclei formation and, since mercury is able to induce oxidative stress that could bring to protein aggregation, we assessed nuclear protein carbonylation by Western Blot. We observed a significant increase in micronuclei formation and 14 carbonylated proteins were identified. Moreover, we used isotope-coded protein label (ICPL) and mass spectrometry analysis of proteins obtained by lysis of purified nuclei, before of tryptic digestion to quantify nuclear proteins affected by mercury. In particular, we examined the effects of mercury that associate a classical genotoxic assay to proteomic effects into the nucleus. The data present direct evidences for mercury genotoxicity, nuclear protein carbonylation, quantitative change in core histones, and the involvement of pseudouridine synthase in mercury toxicity. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 417-425, 2017. PMID- 26888060 TI - Cryo-EM structures of the eukaryotic replicative helicase bound to a translocation substrate. AB - The Cdc45-MCM-GINS (CMG) helicase unwinds DNA during the elongation step of eukaryotic genome duplication and this process depends on the MCM ATPase function. Whether CMG translocation occurs on single- or double-stranded DNA and how ATP hydrolysis drives DNA unwinding remain open questions. Here we use cryo electron microscopy to describe two subnanometre resolution structures of the CMG helicase trapped on a DNA fork. In the predominant state, the ring-shaped C terminal ATPase of MCM is compact and contacts single-stranded DNA, via a set of pre-sensor 1 hairpins that spiral around the translocation substrate. In the second state, the ATPase module is relaxed and apparently substrate free, while DNA intimately contacts the downstream amino-terminal tier of the MCM motor ring. These results, supported by single-molecule FRET measurements, lead us to suggest a replication fork unwinding mechanism whereby the N-terminal and AAA+ tiers of the MCM work in concert to translocate on single-stranded DNA. PMID- 26888063 TI - Structural and biochemical characterization of an RNA/DNA binding motif in the N terminal domain of RecQ4 helicases. AB - The RecQ4 helicase belongs to the ubiquitous RecQ family but its exact role in the cell is not completely understood. In addition to the helicase domain, RecQ4 has a unique N-terminal part that is essential for viability and is constituted by a region homologous to the yeast Sld2 replication initiation factor, followed by a cysteine-rich region, predicted to fold as a Zn knuckle. We carried out a structural and biochemical analysis of both the human and Xenopus laevis RecQ4 cysteine-rich regions, and showed by NMR spectroscopy that the Xenopus fragment indeed assumes the canonical Zn knuckle fold, whereas the human sequence remains unstructured, consistent with the mutation of one of the Zn ligands. Both the human and Xenopus Zn knuckles bind to a variety of nucleic acid substrates, with a mild preference for RNA. We also investigated the effect of a segment located upstream the Zn knuckle that is highly conserved and rich in positively charged and aromatic residues, partially overlapping with the C-terminus of the Sld2-like domain. In both the human and Xenopus proteins, the presence of this region strongly enhances binding to nucleic acids. These results reveal novel possible roles of RecQ4 in DNA replication and genome stability. PMID- 26888061 TI - A Predictive Coexpression Network Identifies Novel Genes Controlling the Seed-to Seedling Phase Transition in Arabidopsis thaliana. AB - The transition from a quiescent dry seed to an actively growing photoautotrophic seedling is a complex and crucial trait for plant propagation. This study provides a detailed description of global gene expression in seven successive developmental stages of seedling establishment in Arabidopsis (Arabidopsis thaliana). Using the transcriptome signature from these developmental stages, we obtained a coexpression gene network that highlights interactions between known regulators of the seed-to-seedling transition and predicts the functions of uncharacterized genes in seedling establishment. The coexpressed gene data sets together with the transcriptional module indicate biological functions related to seedling establishment. Characterization of the homeodomain leucine zipper I transcription factor AtHB13, which is expressed during the seed-to-seedling transition, demonstrated that this gene regulates some of the network nodes and affects late seedling establishment. Knockout mutants for athb13 showed increased primary root length as compared with wild-type (Columbia-0) seedlings, suggesting that this transcription factor is a negative regulator of early root growth, possibly repressing cell division and/or cell elongation or the length of time that cells elongate. The signal transduction pathways present during the early phases of the seed-to-seedling transition anticipate the control of important events for a vigorous seedling, such as root growth. This study demonstrates that a gene coexpression network together with transcriptional modules can provide insights that are not derived from comparative transcript profiling alone. PMID- 26888064 TI - Polyester-based microparticles of different hydrophobicity: the patterns of lipophilic drug entrapment and release. AB - The paper is devoted to the investigation of the effect of polyester hydrophobicity and ability for crystallisation on lipophilic drug loading and release from microparticles fabricated on the base of these polymers. Poly(l lactic acid), poly(d, l-lactic acid) and poly (lactic acid-co-glycolic acid) were synthesised by ring-opening polymerisation using stannous octoate as catalyst, while poly(caprolactone) (PCL) and poly(omega-pentadecalactone) (PPDL) formation was catalysed by lipase. The particles were formed via single emulsion evaporation/diffusion method. The particles obtained were studied using SEM, XRD and DSC methods. The degradation of particles based on different polyesters, entrapment and release of a model hydrophobic drug (risperidone(r)) were thoroughly studied. The effect of particles hydrophobicity and crystallinity on these parameters was of most interest. The drug entrapment is greater for the hydrophobic polymers. Drug release was more rapid from crystalline particles (PLLA, PCL, PPDL), than from amorphous PDLLA and PLGA ones. PMID- 26888065 TI - Epigenetics and Peripheral Artery Disease. AB - The term epigenetics is usually used to describe inheritable changes in gene function which do not involve changes in the DNA sequence. These typically include non-coding RNAs, DNA methylation and histone modifications. Smoking and older age are recognised risk factors for peripheral artery diseases, such as occlusive lower limb artery disease and abdominal aortic aneurysm, and have been implicated in promoting epigenetic changes. This brief review describes studies that have associated epigenetic factors with peripheral artery diseases and investigations which have examined the effect of epigenetic modifications on the outcome of peripheral artery diseases in mouse models. Investigations have largely focused on microRNAs and have identified a number of circulating microRNAs associated with human peripheral artery diseases. Upregulating or antagonising a number of microRNAs has also been reported to limit aortic aneurysm development and hind limb ischemia in mouse models. The importance of DNA methylation and histone modifications in peripheral artery disease has been relatively little studied. Whether circulating microRNAs can be used to assist identification of patients with peripheral artery diseases and be modified in order to improve the outcome of peripheral artery disease will require further investigation. PMID- 26888066 TI - Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity. AB - Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions. PMID- 26888067 TI - The magnitude of severe box jellyfish cases on Koh Samui and Koh Pha-ngan in the Gulf of Thailand. AB - BACKGROUND: Despite recent deaths caused by box jellyfish envenomation occurring on the islands of Samui and Pha-ngan in the Gulf of Thailand, many people do not believe box jellyfish can kill humans and many people dismiss the problem as insignificant. More evidence has been requested from the communities in order to evaluate the need for and the implementation of sustainable prevention measures. We aimed to determine the magnitude of cases of severe stinging by box jellyfish and describe the characteristics of these cases on the islands of Samui and Pha ngan in Surat Thani Province from 1997 to 2015. METHODS: Various strategies were integrated prospectively. Toxic jellyfish networks and surveillance system were established. Outbreak investigations were conducted retrospectively and prospectively from 2008 to 2015. RESULTS: There were 15 box jellyfish cases. A small majority of them were women (60.0) with a median age of 26.0 years (range 5.0-45.0 years). The highest incidence by month were August (33.3%), September and October (20.0%), and July (13.3%). Eight cases occurred on Samui (53.3%), 6 cases on Pha-ngan island (40.0%), and one case on the boat. All cases developed symptoms and signs immediately after being stung. More than half of the cases were unconscious. There were six fatal cases (46.7%). The wound characteristics had an appearance similar to caterpillar tracks or step ladder-like burn marks. Almost all cases involved Chirodropidae. One fatal case received fresh water and ice packs applied to the wounds (16.7%). Among the cases with known first aid, only one out of six fatal cases had vinegar applied to the wounds (16.7%), while haft of six surviving cases received the vinegar treatment. CONCLUSIONS: The islands of Samui and Pha-ngan have the highest incidence of fatal and near fatal box jellyfish cases in Thailand. There is an urgent need for informed pre clinical emergent care. Optimal pre-clinical care is an area of active research. PMID- 26888068 TI - BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis. AB - Adult neurogenesis in the hippocampus is a remarkable phenomenon involved in various aspects of learning and memory as well as disease pathophysiology. Brain derived neurotrophic factor (BDNF) represents a major player in the regulation of this unique form of neuroplasticity, yet the mechanisms underlying its pro neurogenic actions remain unclear. Here, we examined the effects associated with brief (25 min), unilateral infusion of BDNF in the rat dentate gyrus. Acute BDNF infusion induced long-term potentiation (LTP) of medial perforant path-evoked synaptic transmission and, concomitantly, enhanced hippocampal neurogenesis bilaterally, reflected by increased dentate gyrus BrdU + cell numbers. Importantly, inhibition of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) translation through local, unilateral infusion of anti-sense oligodeoxynucleotides (ArcAS) prior to BDNF infusion blocked both BDNF-LTP induction and the associated pro-neurogenic effects. Notably, basal rates of proliferation and newborn cell survival were unaltered in homozygous Arc/Arg3.1 knockout mice. Taken together these findings link the pro-neurogenic effects of acute BDNF infusion to induction of Arc/Arg3.1-dependent LTP in the adult rodent dentate gyrus. PMID- 26888069 TI - Cesarean section delivery and development of food allergy and atopic dermatitis in early childhood. AB - BACKGROUND: Delivery by Cesarean section (CS) may predispose to allergic disorders, presumably due to alterations in the establishment of normal gut microbiota in early infancy. In this study, we sought to investigate the association between CS and physician-diagnosed food allergy and atopic dermatitis during the first 3 years of life, using data from a homogeneous, population based, birth cohort. METHODS: A total of 459 children born and cared for in the same tertiary maternity unit were examined at birth and followed up at 1, 6, 12, 18, 24, 30 and 36 months of age. Participants with symptoms suggestive of food allergy or atopic dermatitis were evaluated by a pediatric allergy specialist to confirm the diagnosis based on well-defined criteria. RESULTS: The rate of CS was 50.8% (n = 233). Food allergy was diagnosed in 24 participants (5.2%) while atopic dermatitis was diagnosed in 62 children (13.5%). Cesarean section (OR 3.15; 95% CI 1.14-8.70), atopic dermatitis of the child (OR 3.01; 95% CI 1.18 7.80), parental atopy (OR 4.33; 95% CI 1.73-12.1), and gestational age (OR 1.57; 95% CI 1.07-2.37) were significant and independent predictors of food allergy. Children with at least one allergic parent delivered by CS had higher probability of developing food allergy compared with vaginally delivered children of non allergic parents (OR 10.0; 95% CI 3.06-32.7). Conversely, the effect of CS on atopic dermatitis was not significant (OR 1.35; 95% CI 0.74-2.47). CONCLUSIONS: Delivery by CS predisposes to the development of food allergy but not atopic dermatitis in early childhood. Cesarean section delivery seems to upregulate the immune response to food allergens, especially in children with allergic predisposition. PMID- 26888071 TI - Best of BJSM online: highlights from the blog, podcasts, YouTube page, Google+ and more! PMID- 26888070 TI - Cascade of neural processing orchestrates cognitive control in human frontal cortex. AB - Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex. PMID- 26888072 TI - Time to return to full training is delayed and recurrence rate is higher in intratendinous ('c') acute hamstring injury in elite track and field athletes: clinical application of the British Athletics Muscle Injury Classification. AB - BACKGROUND: The British Athletics Muscle Injury Classification describes acute muscle injuries and their anatomical site within muscle based on MRI parameters of injury extent. It grades injuries from 0 to 4 and classifies location based on a myofascial (a), musculotendinous (b) or intratendinous (c) description. This is a retrospective cohort study that assessed time to return to full training (TRFT) and injury recurrence in the different British Athletics classifications for hamstring injuries sustained by elite track and field (T&F) athletes over a 4 year period. METHODS: The electronic medical records (EMRs) of 230 elite British T&F athletes were reviewed. Athletes who sustained an acute hamstring injury, with MRI investigation within 7 days of injury, were included. MRI were graded by two musculoskeletal radiologists using the British Athletics Muscle Injury Classification. The EMRs were reviewed by 2 sports physicians, blinded to the new classification; TRFT and injury recurrence were recorded. RESULTS: There were 65 hamstring injuries in 44 athletes (24+/-4.4 years; 28 male, 16 female). TRFT differed among grades (p<0.001). Grade 3 injuries and 'c' injuries took significantly longer and grade 0 injuries took less TRFT. There were 12 re injuries; the injury recurrence rate was significantly higher in intratendinous (c) injuries (p<0.001). There was no difference in re-injury rate between number grades 1-3, hamstring muscle affected, location (proximal vs central vs distal), age or sex. CONCLUSIONS: This study describes the clinical application of the British Athletics Muscle Injury Classification. Different categories of hamstring injuries had different TRFT and recurrence rate. Hamstring injuries that extend into the tendon ('c') are more prone to re-injury and delay TRFT. PMID- 26888073 TI - Network-based methods for identifying critical pathways of complex diseases: a survey. AB - Biological pathways play important roles in the development of complex diseases, such as cancers, which are multifactorial complex diseases that are generally caused by mutation of multiple genes or dysregulation of pathways. It has become one of the most important issues to analyze pathways through combining multiple types of high-throughput data, such as genomics and proteomics, to understand the mechanisms of complex diseases. Currently, several network-based pathway analysis methods have been proposed. In this overview, we review seven major network-based pathway analysis methods and enumerate their benefits and limitations from an algorithmic perspective to provide a reference for the next generation of pathway analysis methods. Finally, we discuss the challenges that the next generation of methods faces. PMID- 26888074 TI - Understanding Climate Adaptation on Public Lands in the Upper Midwest: Implications for Monitoring and Tracking Progress. AB - There are limited examples of efforts to systematically monitor and track climate change adaptation progress in the context of natural resource management, despite substantial investments in adaptation initiatives. To better understand the status of adaptation within state natural resource agencies, we utilized and problematized a rational decision-making framework to characterize adaptation at the level of public land managers in the Upper Midwest. We conducted in-depth interviews with 29 biologists and foresters to provide an understanding of managers' experiences with, and perceptions of, climate change impacts, efforts towards planning for climate change, and a full range of actions implemented to address climate change. While the majority of managers identified climate change impacts affecting their region, they expressed significant uncertainty in interpreting those signals. Just under half of managers indicated planning efforts are underway, although most planning is remote from local management. Actions already implemented include both forward-looking measures and those aimed at coping with current impacts. In addition, cross-scale dynamics emerged as an important theme related to the overall adaptation process. The results hold implications for tracking future progress on climate change adaptation. Common definitions or measures of adaptation (e.g., presence of planning documents) may need to be reassessed for applicability at the level of public land managers. PMID- 26888076 TI - Exploring a New Simulation Approach to Improve Clinical Reasoning Teaching and Assessment: Randomized Trial Protocol. AB - BACKGROUND: Helping trainees develop appropriate clinical reasoning abilities is a challenging goal in an environment where clinical situations are marked by high levels of complexity and unpredictability. The benefit of simulation-based education to assess clinical reasoning skills has rarely been reported. More specifically, it is unclear if clinical reasoning is better acquired if the instructor's input occurs entirely after or is integrated during the scenario. Based on educational principles of the dual-process theory of clinical reasoning, a new simulation approach called simulation with iterative discussions (SID) is introduced. The instructor interrupts the flow of the scenario at three key moments of the reasoning process (data gathering, integration, and confirmation). After each stop, the scenario is continued where it was interrupted. Finally, a brief general debriefing ends the session. System-1 process of clinical reasoning is assessed by verbalization during management of the case, and System-2 during the iterative discussions without providing feedback. OBJECTIVE: The aim of this study is to evaluate the effectiveness of Simulation with Iterative Discussions versus the classical approach of simulation in developing reasoning skills of General Pediatrics and Neonatal-Perinatal Medicine residents. METHODS: This will be a prospective exploratory, randomized study conducted at Sainte-Justine hospital in Montreal, Qc, between January and March 2016. All post-graduate year (PGY) 1 to 6 residents will be invited to complete one SID or classical simulation 30 minutes audio video-recorded complex high-fidelity simulations covering a similar neonatology topic. Pre- and post-simulation questionnaires will be completed and a semistructured interview will be conducted after each simulation. Data analyses will use SPSS and NVivo softwares. RESULTS: This study is in its preliminary stages and the results are expected to be made available by April, 2016. CONCLUSIONS: This will be the first study to explore a new simulation approach designed to enhance clinical reasoning. By assessing more closely reasoning processes throughout a simulation session, we believe that Simulation with Iterative Discussions will be an interesting and more effective approach for students. The findings of the study will benefit medical educators, education programs, and medical students. PMID- 26888077 TI - Multi-functional reactively-sputtered copper oxide electrodes for supercapacitor and electro-catalyst in direct methanol fuel cell applications. AB - This work reports on the concurrent electrochemical energy storage and conversion characteristics of granular copper oxide electrode films prepared using reactive radio-frequency magnetron sputtering at room temperature under different oxygen environments. The obtained films are characterized in terms of their structural, morphological, and compositional properties. X-ray diffraction, X-ray photoelectron spectroscopy and scanning electron microscope studies reveal that granular, single-phase Cu2O and CuO can be obtained by controlling the oxygen flow rate. The electrochemical energy storage properties of the films are investigated by carrying out cyclic voltammetry, galvanostatic charge/discharge and electrochemical impedance spectroscopy tests. The electrochemical analysis reveals that the Cu2O and CuO electrodes have high specific capacitances of 215 and 272 F/g in 6 M KOH solution with a capacity retention of about 80% and 85% after 3000 cycles, respectively. Cyclic voltammetry and chronoamperometry are used to study the electrochemical energy conversion properties of the films via methanol electro-oxidation. The results show that the Cu2O and CuO electrodes are electro-catalytically active and highly stable. PMID- 26888075 TI - Tafenoquine treatment of Plasmodium vivax malaria: suggestive evidence that CYP2D6 reduced metabolism is not associated with relapse in the Phase 2b DETECTIVE trial. AB - BACKGROUND: Tafenoquine (TQ) and primaquine (PQ) are 8-aminoquinolines (8-AQ) with anti-hypnozoite activity against vivax malaria. PQ is the only FDA-approved medicine for preventing relapsing Plasmodium vivax infection and TQ is currently in phase 3 clinical trials for the same indication. Recent studies have provided evidence that cytochrome P450 (CYP) metabolism via CYP2D6 plays a role in PQ efficacy against P. vivax and have suggested that this effect may extend to other 8-AQs, including TQ. Here, a retrospective pharmacogenetic (PGx) investigation was performed to assess the impact of CYP2D6 metabolism on TQ and PQ efficacy in the treatment of P. vivax in the DETECTIVE study (TAF112582), a recently completed, randomized, phase 2b dose-ranging clinical trial. The impact of CYP2D6 on TQ pharmacokinetics (PK) was also investigated in TAF112582 TQ-treated subjects and in vitro CYP metabolism of TQ was explored. A limitation of the current study is that TAF112582 was not designed to be well powered for PGx, thus our findings are based on TQ or PQ efficacy in CYP2D6 intermediate metabolizers (IM), as there were insufficient poor metabolizers (PM) to draw any conclusion on the impact of the PM phenotype on efficacy. METHODS: The impact of genetically predicted CYP2D6 reduced metabolism on relapse-free efficacy six months post dosing of TQ or PQ, both administered in conjunction with chloroquine (CQ), was assessed using exact statistical methods in 198 P. vivax-infected study participants comparing IM to extensive metabolizers (EM). The influence of CYP2D6 metabolizer phenotypes on TQ PK was assessed comparing median TQ area under the curve (AUC). In vitro metabolism of TQ was investigated using recombinant, over expressed human CYP enzymes and human hepatocytes. Metabolite identification experiments were performed using liquid chromatography-mass spectrometry. RESULTS: Reduction of CYP2D6 activity was not associated with an increase in relapse-rate in TQ-treated subjects (p = 0.57). In contrast, and in accordance with recent literature, CYP2D6 IMs were more common (p = 0.05) in PQ-treated subjects who relapsed (50 %) than in subjects who remained relapse-free (17 %). Further, CYP2D6 metabolizer phenotypes had no significant effect on TQ AUC, and only minimal metabolism of TQ could be detected in hepatic in vitro systems. CONCLUSION: Together, these data provide preliminary evidence that in CYP2D6 IMs, TQ efficacy in P. vivax-infected individuals is not diminished to the same extent as PQ. As there were no PMs in either the TQ or PQ treatment arms of TAF112582, no conclusions could be drawn on potential differences in PMs. These findings suggest that differential effects of CYP2D6 metabolism on TQ and PQ efficacy could be a differentiation factor between these 8-AQs, but results remain to be confirmed prospectively in the ongoing phase 3 studies. PMID- 26888078 TI - How planar are planar peptide bonds? PMID- 26888080 TI - Inference and Analysis of Population Structure Using Genetic Data and Network Theory. AB - Clustering individuals to subpopulations based on genetic data has become commonplace in many genetic studies. Inference about population structure is most often done by applying model-based approaches, aided by visualization using distance-based approaches such as multidimensional scaling. While existing distance-based approaches suffer from a lack of statistical rigor, model-based approaches entail assumptions of prior conditions such as that the subpopulations are at Hardy-Weinberg equilibria. Here we present a distance-based approach for inference about population structure using genetic data by defining population structure using network theory terminology and methods. A network is constructed from a pairwise genetic-similarity matrix of all sampled individuals. The community partition, a partition of a network to dense subgraphs, is equated with population structure, a partition of the population to genetically related groups. Community-detection algorithms are used to partition the network into communities, interpreted as a partition of the population to subpopulations. The statistical significance of the structure can be estimated by using permutation tests to evaluate the significance of the partition's modularity, a network theory measure indicating the quality of community partitions. To further characterize population structure, a new measure of the strength of association (SA) for an individual to its assigned community is presented. The strength of association distribution (SAD) of the communities is analyzed to provide additional population structure characteristics, such as the relative amount of gene flow experienced by the different subpopulations and identification of hybrid individuals. Human genetic data and simulations are used to demonstrate the applicability of the analyses. The approach presented here provides a novel, computationally efficient model-free method for inference about population structure that does not entail assumption of prior conditions. The method is implemented in the software NetStruct (available at https://giligreenbaum.wordpress.com/software/). PMID- 26888079 TI - A General Approximation for the Dynamics of Quantitative Traits. AB - Selection, mutation, and random drift affect the dynamics of allele frequencies and consequently of quantitative traits. While the macroscopic dynamics of quantitative traits can be measured, the underlying allele frequencies are typically unobserved. Can we understand how the macroscopic observables evolve without following these microscopic processes? This problem has been studied previously by analogy with statistical mechanics: the allele frequency distribution at each time point is approximated by the stationary form, which maximizes entropy. We explore the limitations of this method when mutation is small (4NMU < 1) so that populations are typically close to fixation, and we extend the theory in this regime to account for changes in mutation strength. We consider a single diallelic locus either under directional selection or with overdominance and then generalize to multiple unlinked biallelic loci with unequal effects. We find that the maximum-entropy approximation is remarkably accurate, even when mutation and selection change rapidly. PMID- 26888081 TI - Ticks associated with domestic dogs and cats in Florida, USA. AB - Voluntary collections of ticks from domestic dogs and cats by veterinary practitioners across Florida, USA, were conducted over a 10 month period. Of the 1337 ticks submitted, five species of ixodid ticks were identified and included Rhipicephalus sanguineus, Amblyomma americanum, A. maculatum, Dermacentor variabilis, and Ixodes scapularis. Most ticks were collected from dogs (98.4%) with the most predominant species being R. sanguineus (94.3%). Of the ticks collected from cats (1.6%), A. americanum were the most common (74%). Only R. sanguineus were collected throughout the state, with the other species collected only in central and north Florida. The tick species collected from dogs and cats represent a risk to these domestic species as well as associated humans for a range of tick-borne diseases in Florida. PMID- 26888082 TI - Case report: severe asymptomatic hyponatremia in Prader-Willi Syndrome. AB - BACKGROUND: Prader-Willi syndrome is a complex neurogenetic, multisystem disorder. Despite the variable endocrine abnormalities and hypothalamic-pituitary axis dysfunction, hyponatremia has been reported in only a few PWS patients. In previously reported PWS individuals, hyponatremia was associated with abnormal fluid intake or during desmopressin treatment. CASE PRESENTATION: We describe an infant with Prader-Willi syndrome who had severe, prolonged asymptomatic hyponatremia without a history of excessive fluid intake or desmopressin treatment. We compare the findings with those of the few other reported cases and describe, for the first time, results of a hypertonic saline infusion test and studies of adrenal cortical function. CONCLUSION: Hyponatremia should be suspected in children with Prader-Willi syndrome, especially in infants with severe failure to thrive. Further studies are needed to determine the pathophysiology of hyponatremia in this syndrome. PMID- 26888083 TI - Margaret McCartney: Mindful of mindfulness. PMID- 26888084 TI - Different regulation of P-glycoprotein function between Caco-2 and Caki-1 cells by ezrin, radixin and moesin proteins. AB - OBJECTIVES: P-glycoprotein (P-gp) mediates efflux of many xenobiotics, including therapeutic drugs, from normal and tumour tissues, and its functional localization on the plasma membrane of cells is regulated by scaffold proteins, such as ezrin, radixin and moesin (ERM proteins). We previously reported that radixin is involved in post-translational regulation of P-gp in hepatocellular carcinoma HepG2 cells and mouse small intestine, but not in mouse kidney. METHODS: Here, we investigated whether the role of ERM proteins in regulation of P-gp transport activity in cancers is the same as that in the corresponding normal tissues, using human colon adenocarcinoma (Caco-2) cells and renal carcinoma (Caki-1) cells. KEY FINDINGS: In Caco-2 cells, radixin silencing alone reduced the P-gp-mediated intracellular accumulation of rhodamine123 (Rho123), while the mRNA level of P-gp was unchanged. Thus, it appears that only radixin among the ERMs regulates P-gp activity in Caco-2 cells. On the other hand, none of the ERM proteins influenced P-gp activity in Caki-1 cells. CONCLUSIONS: The regulation of P-gp by ERM proteins is different between Caco-2 and Caki-1 cells. Moreover, these regulatory properties are the same as those of the corresponding normal tissues, and suggest that tissue-specific differences in the regulation of P-gp by ERM proteins are retained in cancerous tissues. PMID- 26888086 TI - Cognitive Deficits Correlate with White Matter Deterioration in Spinocerebellar Ataxia Type 2. AB - OBJECTIVES: The aim of this study was to explore the relationship between cognitive and white matter deterioration in a group of participants with spinocerebellar ataxia type 2 (SCA2). METHODS: Fourteen genetically confirmed participants with SCA2 and 14 aged-matched controls participated in the study. Diffusion tensor imaging tract-based spatial statistics were performed to analyze structural white matter integrity. Significant group differences in the mean diffusivity were correlated with SCA2 cognitive deficits. RESULTS: Our analysis revealed higher mean diffusivity in the SCA2 group in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Cognitive scores correlated with white matter mean diffusivity in the parahippocampal area, inferior frontal and supramarginal gyri and the stria terminalis. CONCLUSIONS: Our findings show significant correlations between white matter microstructural damage in key areas affected in SCA2 and cognitive deficits. These findings result in a more comprehensive understanding of the effect of the neurodegenerative process in people with SCA2. PMID- 26888085 TI - Membrane Oxidation Enables the Cytosolic Entry of Polyarginine Cell-penetrating Peptides. AB - Arginine-rich peptides can penetrate cells and consequently be used as delivery agents in various cellular applications. The activity of these reagents is often context-dependent, and the parameters that impact cell entry are not fully understood, giving rise to variability and limiting progress toward their usage. Herein, we report that the cytosolic penetration of linear polyarginine peptides is dependent on the oxidation state of the cell. In particular, we find that hypoxia and cellular antioxidants inhibit cell penetration. In contrast, oxidants promote cytosolic cell entry with an efficiency proportional to the level of reactive oxygen species generated within membranes. Moreover, an antibody that binds to oxidized lipids inhibits cell penetration, whereas extracellularly administered pure oxidized lipids enhance peptide transport into cells. Overall, these data indicate that oxidized lipids are capable of mediating the transport of polyarginine peptides across membranes. These data may also explain variability in cell-penetrating peptide performance in different experimental conditions. These new findings therefore provide new opportunities for the rational design of future cell-permeable compounds and for the optimization of delivery protocols. PMID- 26888089 TI - Dispersive solid-phase extraction followed by vortex-assisted dispersive liquid liquid microextraction based on the solidification of a floating organic droplet for the determination of benzoylurea insecticides in soil and sewage sludge. AB - A novel dispersive solid-phase extraction combined with vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet was developed for the determination of eight benzoylurea insecticides in soil and sewage sludge samples before high-performance liquid chromatography with ultraviolet detection. The analytes were first extracted from the soil and sludge samples into acetone under optimized pretreatment conditions. Clean-up of the extract was conducted by dispersive solid-phase extraction using activated carbon as the sorbent. The vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet procedure was performed by using 1-undecanol with lower density than water as the extraction solvent, and the acetone contained in the solution also acted as dispersive solvent. Under the optimum conditions, the linearity of the method was in the range 2-500 ng/g with correlation coefficients (r) of 0.9993-0.9999. The limits of detection were in the range of 0.08-0.56 ng/g. The relative standard deviations varied from 2.16 to 6.26% (n = 5). The enrichment factors ranged from 104 to 118. The extraction recoveries ranged from 81.05 to 97.82% for all of the analytes. The good performance has demonstrated that the proposed methodology has a strong potential for application in the multiresidue analysis of complex matrices. PMID- 26888088 TI - Molecular development of fibular reduction in birds and its evolution from dinosaurs. AB - Birds have a distally reduced, splinter-like fibula that is shorter than the tibia. In embryonic development, both skeletal elements start out with similar lengths. We examined molecular markers of cartilage differentiation in chicken embryos. We found that the distal end of the fibula expresses Indian hedgehog (IHH), undergoing terminal cartilage differentiation, and almost no Parathyroid related protein (PTHrP), which is required to develop a proliferative growth plate (epiphysis). Reduction of the distal fibula may be influenced earlier by its close contact with the nearby fibulare, which strongly expresses PTHrP. The epiphysis-like fibulare however then separates from the fibula, which fails to maintain a distal growth plate, and fibular reduction ensues. Experimental downregulation of IHH signaling at a postmorphogenetic stage led to a tibia and fibula of equal length: The fibula is longer than in controls and fused to the fibulare, whereas the tibia is shorter and bent. We propose that the presence of a distal fibular epiphysis may constrain greater growth in the tibia. Accordingly, many Mesozoic birds show a fibula that has lost its distal epiphysis, but remains almost as long as the tibia, suggesting that loss of the fibulare preceded and allowed subsequent evolution of great fibulo-tibial disparity. PMID- 26888087 TI - Interventions to improve patients' compliance with therapies aimed at lowering glycated hemoglobin (HbA1c) in type 1 diabetes: systematic review and meta analyses of randomized controlled clinical trials of psychological, telecare, and educational interventions. AB - BACKGROUND: Brazilian records on glycemic control in patients with type 1 diabetes show treatment efficacy. Poor patient adherence to therapeutic proposals influences these results and can be associated with social, psychological, and economic aspects, besides others factors. The aim of this study was to evaluate the efficacy of psychological, telecare, and educational interventions to improve treatment compliance among patients with type 1 diabetes. Compliance was assessed indirectly using reduction of glycated hemoglobin (HbA1c) as the principal outcome measure. METHODS: Systematic review and meta-analyses of randomized controlled clinical trials (RCTs) were performed using Medline, Embase, Cochrane and Scopus databases up to April 2015. The following medical subject headings were used: Diabetes Mellitus, Type 1, Patient Compliance or Adherence, Hemoglobin A, glycated, and Randomized Controlled Trial. The principal outcome was change in HbA1c between baseline and follow-up. Where appropriate, trials were combined in meta-analysis using fixed effects models. RESULTS: From 191 articles initially identified, 57 were full text reviewed, and 19 articles met the inclusion criteria providing data from 1782 patients (49.4 % males, age 18 years). The RCTs (2 to 24 months in duration) were divided into four groups according to type of intervention: psychology (seven studies; 818 patients), telecare (six studies; 494 patients); education (five studies; 349 patients), and psychoeducation (one study; 153 patients). All studies reported some type of adherence measurement of the interventions. Decrease in HbA1c was observed after psychology (MD -0.310; 95 % CI, -0.599 to -0.0210, P = 0.035) but not after telecare (MD -0.124 %; 95 % CI, -0.268, 0.020; P = 0.090) or educational (MD -0.001; 95 % CI, -0.202, 0.200; P = 0.990) interventions. CONCLUSION: Psychological approaches to improve adherence to diabetes care treatment modestly reduced HbA1c in patients with type 1 diabetes; telecare and education interventions did not change glycemic control. However, the limited number of studies included as well as their methodological quality should be taken into account. PMID- 26888090 TI - Decreasing incidence of ruptured abdominal aortic aneurysm already before start of screening. AB - BACKGROUND: The aim of this study was to evaluate whether screening for abdominal aortic aneurysm (AAA) has led to a decrease in ruptured AAA (rAAA) incidence. METHOD: The Malmo population was evaluated regarding the incidence of rAAA and elective AAA surgery 4 years before and after start of AAA-screening in 2010. Data from 1971 to 1986 (J Vasc Surg 18:74-80, 1993) and 2000-2004 (J Vasc Surg 44:237-43, 2006), enabled analysis of trends over time. RESULTS: Analysis of time periods 1971-1986, 2000-2004, 2006-2010 and 2010-2014 showed an incidence of rAAA of 5.6 (4.9-6.3), 10.6 (8.9-12.4), 6.1 (4.6-7.6) and 4.0 (2.9-5.1), respectively. In men aged 60-69 years the incidences were 16.0 (10.7-21.3), 45.6 (27.7-63.4), 19.3 (9.2-35.3) and 8.9 (2.8-20.6), respectively. The incidences of elective AAA surgery in men aged 60-69 years were 22.9 (16.5-29.2), 34.6 (19.1-50.2), 9.7 (1.2 18.5) and 44.2 (27.0-61.6), respectively. CONCLUSIONS: A decrease in incidence of rAAA in men was evident before the implementation of screening. We were yet not able to demonstrate a certain reduction in rAAA incidence after the start of screening. PMID- 26888091 TI - Prevalence and risk factors for pulmonary arterial hypertension in end-stage renal disease patients undergoing continuous ambulatory peritoneal dialysis. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied. RESULTS: Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E') (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are major risk factors for PAH. CONCLUSION: We observed a high incidence of PAH in ESRD patients undergoing CAPD. Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are high-risk factors for PAH in ESRD patients undergoing CAPD. PMID- 26888092 TI - HSP70 mRNA expression by cells of the epithelial rest of Malassez due to mechanical forces in vitro. AB - BACKGROUND: The purpose of the present study was to examine the in vitro responses of ERM cells under the combination of centrifugal and compression forces, in terms of their expression of HSP70 mRNA. METHODS: The ERM cells were positive for CK19 indicating that they were derived from the odontogenic epithelium. Cultured ERM cells were applied centrifugal force and compressing force at one to three times as mechanical forces. After addition of forces, cells were observed using scanning electron microscope (SEM) and were measured expression of HSP70 mRNA by RT-PCR. RESULTS: SEM observations showed the cells were flattened immediately after the application of mechanical force, but nuclear protrusions recovered the same as the control 3 h later. A significantly higher expression of HSP70 mRNA was observed in ERM cells under mechanical force compared with the control, but it gradually decreased with time. No accumulation of HSP70 mRNA expression occurred with intermittent force. However, the expression of HSP70 mRNA with intermittent force repeated 3 times was significantly higher compared with intermittent force applied only once or twice. CONCLUSIONS: These findings suggest that ERM cells express HSP70 mRNA in response to mechanical force, and that intermittent force maintains the level of HSP70 mRNA expression. PMID- 26888093 TI - Meta-analysis with missing study-level sample variance data. AB - We consider a study-level meta-analysis with a normally distributed outcome variable and possibly unequal study-level variances, where the object of inference is the difference in means between a treatment and control group. A common complication in such an analysis is missing sample variances for some studies. A frequently used approach is to impute the weighted (by sample size) mean of the observed variances (mean imputation). Another approach is to include only those studies with variances reported (complete case analysis). Both mean imputation and complete case analysis are only valid under the missing-completely at-random assumption, and even then the inverse variance weights produced are not necessarily optimal. We propose a multiple imputation method employing gamma meta regression to impute the missing sample variances. Our method takes advantage of study-level covariates that may be used to provide information about the missing data. Through simulation studies, we show that multiple imputation, when the imputation model is correctly specified, is superior to competing methods in terms of confidence interval coverage probability and type I error probability when testing a specified group difference. Finally, we describe a similar approach to handling missing variances in cross-over studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888094 TI - Higher endogenous methionine in transgenic Arabidopsis seeds affects the composition of storage proteins and lipids. AB - Previous in vitro studies demonstrate that exogenous application of the sulfur containing amino acid methionine into cultured soybean cotyledons and seedlings reduces the level of methionine-poor storage proteins and elevates those that are methionine-rich. However, the effect of higher endogenous methionine in seeds on the composition of storage products in vivo is not studied yet. We have recently produced transgenic Arabidopsis seeds having significantly higher levels of methionine. In the present work we used these seeds as a model system and profiled them for changes in the abundances of 12S-globulins and 2S-albumins, the two major groups of storage proteins, using 2D-gels and MALDI-MS detection. The findings suggest that higher methionine affects from a certain threshold the accumulation of several subunits of 12S-globulins and 2S-albumins, regardless of their methionine contents, resulting in higher total protein contents. The mRNA abundances of most of the genes encoding these proteins were either correlated or not correlated with the abundances of these proteins, implying that methionine may regulate storage proteins at both transcriptional and post-transcriptional levels. The elevations in total protein contents resulted in reduction of total lipids and altered the fatty acid composition. Altogether, the data provide new insights into the regulatory roles of elevated methionine levels on seed composition. PMID- 26888095 TI - Rapamycin attenuates acute lung injury induced by LPS through inhibition of Th17 cell proliferation in mice. AB - Th17 cells have been confirmed to increase neutrophils through cytokine secretions. ALI/ARDS are characterized as neutrophil infiltration in inflammation cases; however, there is conflicting information concerning the role of Th17 cells in ALI/ARDS, as well as their potential treatment value. We measured Th17 linear cytokines in the plasma of patients with sepsis-related ARDS. The consistently high levels of IL-17 and IL-22 in the nonsurvivors suggested that overreaction of the Th17-mediated immune response may be a risk factor for poor outcomes. Th17 linear cytokines were also increased in an LPS-induced murine model of acute lung injury, along with neutrophil accumulation. The mice that completely lacked IL-17 failed to accumulate and activate neutrophils. Lung inflammation was obviously attenuated in the IL-17(-)/(-) mice. Meanwhile, the neutrophil count was markedly increased in the healthy WT mice challenged with recombinant IL-22 and IL-17. Rapamycin attenuated lung injury by inhibiting the differentiation of Th17 cells through RORgammat and STAT3 dysfunction. Furthermore, we demonstrated that SOCS3 and Gfi1, which were responsible for the molecular suppression of RORgammat and STAT3, were up-regulated by rapamycin. These results point toward a pivotal view to treatment of ALI through weakening the proliferation of Th17 cells with rapamycin. PMID- 26888096 TI - Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus. AB - PURPOSE: This study investigates the involvement of liver dysfunction in the modulation of paracetamol pharmacokinetic profile in genotype-4 HCV patients treated with either paracetamol alone (Para) or in combination with caffeine (Para-Caf). METHODS: Twenty healthy volunteers and 20 Child-Pugh B HCV patients, each divided into two equal subgroups, were examined, whose liver/kidney functions were correlated with their main clinical manifestation. After an overnight fasting, healthy and hepatic subjects received either a single dose of Para (1000 mg paracetamol) or Para-Caf (1000 mg paracetamol/130 mg caffeine). Two milliliters of saliva samples were collected prior to and at different time intervals after drug administration and analyzed using HPLC. RESULTS: There was a noticeable increase in the mean concentration time profile of salivary paracetamol concentrations in hepatic patients, with concomitant decrease in paracetamol clearance (CLT), along with induction in the primary pharmacokinetic (PK) parameters, C max, AUC(0-8 h) and AUC(0-infinity) (by about 95, 82, and 64 %, respectively, after treatment with Para, and 98, 96, and 101 %, respectively, after treatment with Para-Caf), when compared with the corresponding parameters in healthy subjects. Additionally, the healthy subjects treated with Para-Caf exhibited bioinequivalent increase in C max, K a, and t 1/2 with decrease in T max when compared with the healthy individuals treated with Para alone. A similar pattern was recorded in hepatic patients after addition of caffeine to paracetamol, with even augmented significant increase in K a and t 1/2 (by 100 and 32 %, respectively). CONCLUSIONS: Liver dysfunction modified the PK of paracetamol expressed as earlier effective paracetamol concentration, with obvious decrease in its clearance. Caffeine induced faster absorption (evidenced by shorter T max and higher K a) and prolonged t 1/2 of paracetamol, the effects that were more profound in hepatic patients. Further studies are needed to evaluate the influence of liver damage on paracetamol pharmacokinetics whenever repeated dosing is applied, to avoid possible drug accumulation. PMID- 26888097 TI - Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice. AB - Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death. PMID- 26888098 TI - An asymmetric outer retinal response to drifting sawtooth gratings. AB - Electroretinogram (ERG) studies have demonstrated that the retinal response to temporally modulated fast-ON and fast-OFF sawtooth flicker is asymmetric. The response to spatiotemporal sawtooth stimuli has not yet been investigated. Perceptually, such drifting gratings or diamond plaids shaded in a sawtooth pattern appear brighter when movement produces fast-OFF relative to fast-ON luminance profiles. The neural origins of this illusion remain unclear (although a retinal basis has been suggested). Thus we presented toad eyecups with sequential epochs of sawtooth, sine-wave, and square-wave gratings drifting horizontally across the retina at temporal frequencies of 2.5-20 Hz. All ERGs revealed a sustained direct-current (DC) transtissue potential during drift and a peak at drift offset. The amplitudes of both phenomena increased with temporal frequency. Consistent with the human perceptual experience of sawtooth gratings, the sustained DC potential effect was greater for fast-OFF cf. fast-ON sawtooth. Modeling suggested that the dependence of temporal luminance contrast on stimulus device frame rate contributed to the temporal frequency effects but could not explain the divergence in response amplitudes for the two sawtooth profiles. The difference between fast-ON and fast-OFF sawtooth profiles also remained following pharmacological suppression of postreceptoral activity with tetrodotoxin (TTX), 2 amino-4-phosphonobutric acid (APB), and 2,3 cis-piperidine dicarboxylic acid (PDA). Our results indicate that the DC potential difference originates from asymmetries in the photoreceptoral response to fast-ON and fast-OFF sawtooth profiles, thus pointing to an outer retinal origin for the motion-induced drifting sawtooth brightness illusion. PMID- 26888099 TI - Neuromagnetic correlates of adaptive plasticity across the hand-face border in human primary somatosensory cortex. AB - It is well established that permanent or transient reduction of somatosensory inputs, following hand deafferentation or anesthesia, induces plastic changes across the hand-face border, supposedly responsible for some altered perceptual phenomena such as tactile sensations being referred from the face to the phantom hand. It is also known that transient increase of hand somatosensory inputs, via repetitive somatosensory stimulation (RSS) at a fingertip, induces local somatosensory discriminative improvement accompanied by cortical representational changes in the primary somatosensory cortex (SI). We recently demonstrated that RSS at the tip of the right index finger induces similar training-independent perceptual learning across the hand-face border, improving somatosensory perception at the lips (Muret D, Dinse HR, Macchione S, Urquizar C, Farne A, Reilly KT.Curr Biol24: R736-R737, 2014). Whether neural plastic changes across the hand-face border accompany such remote and adaptive perceptual plasticity remains unknown. Here we used magnetoencephalography to investigate the electrophysiological correlates underlying RSS-induced behavioral changes across the hand-face border. The results highlight significant changes in dipole location after RSS both for the stimulated finger and for the lips. These findings reveal plastic changes that cross the hand-face border after an increase, instead of a decrease, in somatosensory inputs. PMID- 26888100 TI - Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis. AB - The cerebellum was historically considered a brain region dedicated to motor control, but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements. PMID- 26888101 TI - Saccades create similar mislocalizations in visual and auditory space. AB - Orienting our eyes to a light, a sound, or a touch occurs effortlessly, despite the fact that sound and touch have to be converted from head- and body-based coordinates to eye-based coordinates to do so. We asked whether the oculomotor representation is also used for localization of sounds even when there is no saccade to the sound source. To address this, we examined whether saccades introduced similar errors of localization judgments for both visual and auditory stimuli. Sixteen subjects indicated the direction of a visual or auditory apparent motion seen or heard between two targets presented either during fixation or straddling a saccade. Compared with the fixation baseline, saccades introduced errors in direction judgments for both visual and auditory stimuli: in both cases, apparent motion judgments were biased in direction of the saccade. These saccade-induced effects across modalities give rise to the possibility of shared, cross-modal location coding for perception and action. PMID- 26888102 TI - Spectral breadth and laminar distribution of thalamocortical inputs to A1. AB - The GABAergic agonist muscimol is used to inactivate brain regions in order to reveal afferent inputs in isolation. However, muscimol's use in primary auditory cortex (A1) has been questioned on the grounds that it may unintentionally suppress thalamocortical inputs. We tested whether muscimol can preferentially suppress cortical, but not thalamocortical, circuits in urethane-anesthetized mice. We recorded tone-evoked current source density profiles to determine frequency receptive fields (RFs) for three current sinks: the "layer 4" sink (fastest onset, middle-layer sink) and current sinks 100 MUm above ("layer 2/3") and 300 MUm below ("layer 5/6") the main input. We first determined effects of muscimol dose (0.01-1 mM) on the characteristic frequency (CF) tone-evoked layer 4 sink. An "ideal" dose (100 MUM) had no effect on CF-evoked sink onset latency or initial response but reduced peak amplitude by >80%, implying inhibition of intracortical, but not thalamocortical, activity. We extended the analysis to current sinks in layers 2/3 and 5/6 and for all three sinks determined RF breadth (quarter-octave steps, 20 dB above CF threshold). Muscimol reduced RF breadth 42% in layer 2/3 (from 2.4 +/- 0.14 to 1.4 +/- 0.11 octaves), 14% in layer 4 (2.2 +/- 0.12 to 1.9 +/- 0.10 octaves), and not at all in layer 5/6 (1.8 +/- 0.10 to 1.7 +/- 0.12 octaves). The results provide an estimate of the laminar and spectral extent of thalamocortical projections and support the hypothesis that intracortical pathways contribute to spectral integration in A1. PMID- 26888104 TI - A common control signal and a ballistic stage can explain the control of coordinated eye-hand movements. AB - Voluntary control has been extensively studied in the context of eye and hand movements made in isolation, yet little is known about the nature of control during eye-hand coordination. We probed this with a redirect task. Here subjects had to make reaching/pointing movements accompanied by coordinated eye movements but had to change their plans when the target occasionally changed its position during some trials. Using a race model framework, we found that separate effector specific mechanisms may be recruited to control eye and hand movements when executed in isolation but when the same effectors are coordinated a unitary mechanism to control coordinated eye-hand movements is employed. Specifically, we found that performance curves were distinct for the eye and hand when these movements were executed in isolation but were comparable when they were executed together. Second, the time to switch motor plans, called the target step reaction time, was different in the eye-alone and hand-alone conditions but was similar in the coordinated condition under assumption of a ballistic stage of ~40 ms, on average. Interestingly, the existence of this ballistic stage could predict the extent of eye-hand dissociations seen in individual subjects. Finally, when subjects were explicitly instructed to control specifically a single effector (eye or hand), redirecting one effector had a strong effect on the performance of the other effector. Taken together, these results suggest that a common control signal and a ballistic stage are recruited when coordinated eye-hand movement plans require alteration. PMID- 26888103 TI - Hypergravity within a critical period impacts on the maturation of somatosensory cortical maps and their potential for use-dependent plasticity in the adult. AB - We investigated experience-dependent plasticity of somatosensory maps in rat S1 cortex during early development. We analyzed both short- and long-term effects of exposure to 2G hypergravity (HG) during the first 3 postnatal weeks on forepaw representations. We also examined the potential of adult somatosensory maps for experience-dependent plasticity after early HG rearing. At postnatal day 22, HG was found to induce an enlargement of cortical zones driven by nail displacements and a contraction of skin sectors of the forepaw map. In these remaining zones serving the skin, neurons displayed expanded glabrous skin receptive fields (RFs). HG also induced a bias in the directional sensitivity of neuronal responses to nail displacement. HG-induced map changes were still found after 16 wk of housing in normogravity (NG). However, the glabrous skin RFs recorded in HG rats decreased to values similar to that of NG rats, as early as the end of the first week of housing in NG. Moreover, the expansion of the glabrous skin area and decrease in RF size normally induced in adults by an enriched environment (EE) did not occur in the HG rats, even after 16 wk of EE housing in NG. Our findings reveal that early postnatal experience critically and durably shapes S1 forepaw maps and limits their potential to be modified by novel experience in adulthood. PMID- 26888105 TI - Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala. AB - A large majority of neurons in the superficial layer of the dorsal horn projects to the lateral parabrachial nucleus (LPB). LPB neurons then project to the capsular part of the central amygdala (CeA; CeC), a key structure underlying the nociception-emotion link. LPB-CeC synaptic transmission is enhanced in various pain models by using electrical stimulation of putative fibers of LPB origin in brain slices. However, this approach has limitations for examining direct monosynaptic connections devoid of directly stimulating fibers from other structures and local GABAergic neurons. To overcome these limitations, we infected the LPB of rats with an adeno-associated virus vector expressing channelrhodopsin-2 and prepared coronal and horizontal brain slices containing the amygdala. We found that blue light stimulation resulted in monosynaptic excitatory postsynaptic currents (EPSCs), with very small latency fluctuations, followed by a large polysynaptic inhibitory postsynaptic current in CeC neurons, regardless of the firing pattern type. Intraplantar formalin injection at 24 h before slice preparation significantly increased EPSC amplitude in late firing type CeC neurons. These results indicate that direct monosynaptic glutamatergic inputs from the LPB not only excite CeC neurons but also regulate CeA network signaling through robust feed-forward inhibition, which is under plastic modulation in response to persistent inflammatory pain. PMID- 26888107 TI - Odors enhance slow-wave activity in non-rapid eye movement sleep. AB - Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 +/- 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. PMID- 26888108 TI - Correlations between prefrontal neurons form a small-world network that optimizes the generation of multineuron sequences of activity. AB - Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g., working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a by-product of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization-they have a small-world topology. However, until now it has not been possible to directly link small-world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate data sets that have identical levels of network activity at every point in time but nevertheless represent various network topologies. We call this method shuffling activity to rearrange correlations (SHARC). We found that only surrogate data sets based on the actual small-world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small world data sets contained many more sequences than surrogate data sets with randomly arranged correlations. Surprisingly, small-world data sets also outperformed data sets in which correlations were maximally clustered. Thus the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity. PMID- 26888106 TI - Incorporating spike-rate adaptation into a rate code in mathematical and biological neurons. AB - For a slowly varying stimulus, the simplest relationship between a neuron's input and output is a rate code, in which the spike rate is a unique function of the stimulus at that instant. In the case of spike-rate adaptation, there is no unique relationship between input and output, because the spike rate at any time depends both on the instantaneous stimulus and on prior spiking (the "history"). To improve the decoding of spike trains produced by neurons that show spike-rate adaptation, we developed a simple scheme that incorporates "history" into a rate code. We utilized this rate-history code successfully to decode spike trains produced by 1) mathematical models of a neuron in which the mechanism for adaptation (IAHP) is specified, and 2) the gastropyloric receptor (GPR2), a stretch-sensitive neuron in the stomatogastric nervous system of the crab Cancer borealis, that exhibits long-lasting adaptation of unknown origin. Moreover, when we modified the spike rate either mathematically in a model system or by applying neuromodulatory agents to the experimental system, we found that changes in the rate-history code could be related to the biophysical mechanisms responsible for altering the spiking. PMID- 26888109 TI - Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brain stem preparation of rat. AB - Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brain stem are capable of producing respiratory rhythm. To test this theory we a priori transected brain stem preparations before reperfusion and reoxygenation at 4 rostrocaudal levels: 1.5 mm caudal to obex (n = 5), at obex (n = 5), and 1.5 (n = 7) and 3 mm (n = 6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic and vagal nerves and lumbar spinal expiratory motor output. Preparations with a priori transection at level of the caudal brain stem did not produce stable rhythmic respiratory bursting, even when the arterial chemoreceptors were stimulated with sodium cyanide (NaCN). Reperfusion of brain stems that preserved the pre-Botzinger complex (pre-BotC) showed spontaneous and sustained rhythmic respiratory bursting at low phrenic nerve activity (PNA) amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BotC burstlet-type rhythm. Conserving circuitry up to the pontomedullary junction consistently produced robust high-amplitude PNA at lower burst rates, whereas sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high amplitude PNA had 1:2 quantal relation, with burstlets appearing to trigger high amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata and confirm the pre-BotC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation. PMID- 26888110 TI - Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy. AB - We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy. PMID- 26888112 TI - Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention. AB - The beta-2 and beta-3 adrenergic receptors (ADRB2 and ADRB3) are thought to play a role in energy expenditure and lipolysis. However, the effects of the ADRB2 glutamine (Gln) 27 glutamic acid (glutamate) (Glu) and ADRB3 tryptophan (Trp) 64 arginine (Arg) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program. One hundred seventy three healthy overweight and obese participants (91 women, 82 men) aged 18-50 years participated in a 22-week-long intervention based on a hypocaloric diet and exercise. They were randomly assigned to 1 of 4 groups: strength, endurance, strength and endurance combined, and physical activity recommendations only. Body weight, body mass index (BMI), and body composition variables were assessed before and after the intervention. Genetic analysis was carried out according to standard protocols. No effect of the ADRB2 gene was shown on final weight, BMI, or body composition, although in the supervised male group, Glu27 carriers tended to have greater weight (p = 0.019, 2.5 kg) and BMI (p = 0.019, 0.88 kg/m(2)) reductions than did noncarriers. There seems to be an individual effect of the ADRB3 polymorphism on fat mass (p = 0.004) and fat percentage (p = 0.036), in addition to an interaction with exercise for fat mass (p = 0.038). After the intervention, carriers of the Arg64 allele had a greater fat mass and fat percentage than did noncarriers (p = 0.004, 2.8 kg). In conclusion, the ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms may influence weight loss and body composition, although the current evidence is weak; however, further studies are necessary to clarify their roles. PMID- 26888113 TI - An unsupervised eye blink artifact detection method for real-time electroencephalogram processing. AB - Electroencephalogram (EEG) is easily contaminated by unwanted physiological artifacts, among which electrooculogram (EOG) artifacts due to eye blinking are known to be most dominant. The eye blink artifacts are reported to affect theta and alpha rhythms of frontal EEG signals, and hard to be accurately detected in an unsupervised way due to large individual variability. In this study, we propose a new method for detecting eye blink artifacts automatically in real time without using any labeled training data. The proposed method combined our previous method for detecting eye blink artifacts based on digital filters with an automatic thresholding algorithm. The proposed method was evaluated using EEG data acquired from 24 participants. Two conventional algorithms were implemented and their performances were compared with that of the proposed method. The main contributions of this study are (1) confirming that individual thresholding is necessary for artifact detection, (2) proposing a novel algorithm structure to detect blink artifacts in a real-time environment without any a priori knowledge, and (3) demonstrating that the length of training data can be minimized through the use of a real-time adaption procedure. PMID- 26888114 TI - BIRC3 is a novel driver of therapeutic resistance in Glioblastoma. AB - Genome-wide analysis of glioblastoma (GBM) reveals pervasive aberrations in apoptotic signaling pathways that collectively contribute to therapeutic resistance. Inhibitors of apoptosis proteins (IAP) exert critical control on the terminal segment of apoptosis leading to apoptosis evasion. In this study, we uncover a unique role for BIRC3, as an IAP that is critical in GBM in response to therapy. Using the TCGA dataset of 524 unique samples, we identify BIRC3 is the only IAP whose differential expression is associated with long-term survival in GBM patients. Using patient tissue samples we further show that BIRC3 expression increases with recurrence. When extrapolated to a preclinical model of a human GBM cell line, we find an increase in BIRC3 expression in response to irradiation (RT) and temozolomide (TMZ) treatment. More importantly, we mechanistically implicate STAT3 and PI3K signaling pathways as drivers of RT-induced up regulation of BIRC3 expression. Lastly, we demonstrate that both in-vivo and in vitro BIRC3 up-regulation results in apoptosis evasion and therapeutic resistance in GBM. Collectively, our study identifies a novel translational and targetable role for BIRC3 expression as a predictor of aggressiveness and therapeutic resistance to TMZ and RT mediated by STAT3 and PI3K signaling in GBM. PMID- 26888115 TI - Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome. AB - AIMS: This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome. MATERIALS AND METHODS: Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded. RESULTS: Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome. CONCLUSIONS: In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy. PMID- 26888116 TI - Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome. AB - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration-approved drug therapies. Melatonin is a well-known anti inflammatory molecule, which has proven to be effective in ALI induced by many conditions. Emerging studies suggest that the NLRP3 inflammasome plays a critical role during ALI. How melatonin directly blocks activation of the NLRP3 inflammasome in ALI remains unclear. In this study, using an LPS-induced ALI mouse model, we found intratracheal (i.t.) administration of melatonin markedly reduced the pulmonary injury and decreased the infiltration of macrophages and neutrophils into lung. During ALI, the NLRP3 inflammasome is significantly activated with a large amount of IL-1beta and the activated caspase-1 occurring in the lung. Melatonin inhibits the activation of the NLRP3 inflammasome by both suppressing the release of extracellular histones and directly blocking histone induced NLRP3 inflammasome activation. Notably, i.t. route of melatonin administration opens a more efficient therapeutic approach for treating ALI. PMID- 26888111 TI - Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology. AB - Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared with conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial subpopulations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation, and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal subpopulation have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients. PMID- 26888117 TI - A role for circadian clock in metabolic disease. AB - Many human behaviors and physiological activities show circadian rhythms. Circadian rhythms generated by central and peripheral clocks maintain homeostasis, including the regulation of metabolic processes. Biological rhythmicity is important for metabolic health, but circadian rhythms are affected and impaired by nocturnal activities and irregular food intake in modern society. Disruption of sleep is an established risk factor for diabetes and is known to promote systemic metabolic dysfunction in both humans and rodents. Metabolic stress promotes circadian clock disorders and modulation of clock gene expression has a causal role in the development of metabolic dysfunction. Maintenance of a physiological circadian rhythm is crucial for metabolic health and is an important strategy for combating obesity. PMID- 26888119 TI - Circadian clock and the onset of cardiovascular events. AB - The onset of cardiovascular diseases often shows time-of-day variation. Acute myocardial infarction or ventricular arrhythmia such as ventricular tachycardia occurs mainly in the early morning. Multiple biochemical and physiological parameters show circadian rhythm, which may account for the diurnal variation of cardiovascular events. These include the variations in blood pressure, activity of the autonomic nervous system and renin-angiotensin axis, coagulation cascade, vascular tone and the intracellular metabolism of cardiomyocytes. Importantly, the molecular clock system seems to underlie the circadian variation of these parameters. The center of the biological clock, also known as the central clock, exists in the suprachiasmatic nucleus. In contrast, the molecular clock system is also activated in each cell of the peripheral organs and constitute the peripheral clock. The biological clock system is currently considered to have a beneficial role in maintaining the homeostasis of each organ. Discoordination, however, between the peripheral clock and external environment could potentially underlie the development of cardiovascular events. Therefore, understanding the molecular and cellular pathways by which cardiovascular events occur in a diurnal oscillatory pattern will help the establishment of a novel therapeutic approach to the management of cardiovascular disorders. PMID- 26888118 TI - Structure and functions of angiotensinogen. AB - Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin-angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of structural and functional studies is highlighted to focus on the increasing recognition that AGT exerts effects beyond being a sole provider of angiotensin peptides. PMID- 26888120 TI - Hypertension and obstructive sleep apnea. AB - Obstructive sleep apnea (OSA) is a major modifiable risk factor of hypertension and hypertensive patients with OSA are at increased risk for cardiovascular diseases. A substantial number of studies have revealed that OSA and hypertension have synergistic effects on the cardiovascular system and, therefore, it is clinically important and relevant to increase our understanding of the pathophysiological interactions between OSA and hypertension. In our present review, after briefly reviewing the characteristics and pathophysiological effects of OSA, we focus on the current understanding of OSA-associated hypertension, the potential approaches for treatment of OSA and the effect of OSA treatment on hypertension management. We hope our present review will shed light for future studies that investigate effective therapeutic strategies to simultaneously improve the management of OSA and hypertension. PMID- 26888121 TI - The need for noninvasive methods to monitor hemodynamics in hypertension therapy. PMID- 26888123 TI - Demographic differences between funerary caves and megalithic graves of northern Spanish Late Neolithic/Early Chalcolithic. AB - OBJECTIVES: The study focuses on the estimation of demographic parameters of Late Neolithic/Early Chalcolithic (mid 4th-early 3rd millenniums cal. BC) burial sites from the La Rioja region (Ebro valley, northern Spain) to identify demographic characteristics. MATERIALS AND METHODS: The human remains come from three caves (Las Yurdinas II, Pena Larga, and La Pena de Maranon) and three megalithic graves (Alto de la Huesera, San Martin, and Pena Guerra II). The total skeletal sample consists of a minimum of 261 individuals, 149 being buried in caves and 112 in megalithic graves. Data based on age and sex estimation are analyzed using abridged life tables, mortality rates, and sex ratios. RESULTS: A systematic bias against children under 5 years of age is detected both in caves (5 q0 = 187.92%) and megalithic graves (5 q0 = 71.43%) but also against some juveniles and adults compared with population models, though a statistically significant greater lack of infants is worth noting in the megaliths (t-test, P = 0.012). Moreover, a significant divergence in sex ratios (chi(2) , P = 0.002) is also identified between site types, clearly prioritizing women in caves (sex ratio = 0.45) and men in megalithic graves (sex ratio = 1.33). CONCLUSIONS: This evidence is interpreted as the result of different selective burial patterns. The mortuary variability could lie behind intragroup differential status relationships, though the hypothesis of two populations performing distinct funerary practices in a small region cannot be rejected at the present state of the research. Am J Phys Anthropol 160:284-297, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26888124 TI - [New insight into phoniatrics in China]. PMID- 26888122 TI - Topologically nontrivial bismuth(111) thin films. AB - Using high-resolution angle-resolved photoemission spectroscopy (ARPES), the topological property of the three-dimensional Bi(111) films grown on the Bi2Te3(111) substrate were studied. Very different from the bulk Bi, we found another surface band near the point besides the two well-known surface bands on the 30 nm films. With this new surface band, the bulk valence band and the bulk conduction band can be connected by the surface states in the Bi(111)/Bi2Te3 films. Our band mapping revealed odd number of Fermi crossings of the surface bands, which provided new experimental evidences that Bi(111)/Bi2Te3 films of a certain thickness can be topologically nontrivial in three dimension. PMID- 26888126 TI - [A retrospective study on the diagnosis and treatment of vocal folds white lesions]. AB - OBJECTIVE: To analyze the pathogenesis and clinical features of the vocal fold white lesions, and to investigate the principles of the diagnosis and treatment. METHODS: One hundred and fifty-six cases of vocal fold white lesions encountered between January 2006 and December 2013 were analyzed. All patients had bilateral vocal folds whitening under laryngoscopic examination, and all the patients had been observed over three months. There were 135 males and 21 females in the study, the age ranged from 18 to 60 years, with the mean age of (38.8+/-8.1) years old. All patients had a history of vocal abuse, with moderate-severe degree of voice disorder. RESULTS: After a month of voice rest and suitable treatment, the result of reexamination showed that the symptoms faded away in 81 cases (51.9%), with the voice recuperated; the range of white lesion was reduced with the voice improving in 71 cases (45.4%); the range of white lesion was not obviously changed in 4 cases (2.6%), the pathological examination in these 4 cases showed moderate-severe dysplasia in two cases, and the surgical treatment was applied for them. Two months later, the reexamination showed 26 male cases still had vocal fold white lesion with various degree; and three months later, only 7 male cases retained mild vocal fold white lesion. CONCLUSION: Histopathologically, not all vocal fold white lesions were laryngeal precancerous lesions, and not all of these patients should be treated surgically. PMID- 26888125 TI - [Clinical study of the influence of laryngopharyngeal reflux on quality of life in patients with dysphonia]. AB - OBJECTIVE: To explore the morbidity of laryngopharyngeal reflux in patients with dysphonic diseases and to investigate the influence of LPR on the patients. METHODS: One hundred and twenty-seven patients with dysphonic diseases were encountered in Peking University of the People Hospital. Under the agreement, the patients were asked to fill in the scales of RSI, RFS, VHI and SF-36.24-hour ambulatory double pH monitoring was applied to diagnose LPR definitely. 2643 volunteers were recruited to fill in the RSI scale through physical examination, outpatient, the ward and web survey. RESULTS: 46.46% (59/127) patients were diagnosed with LPR definitely. 1241 of 2643 volunteer, who filled in the RSI, score more than zero in the first entry of hoarseness or dysphonia, 65.0% (807/1241) of them, scoring 13 points or higher, were diagnosed with clinically suspected LPR. Based on the 24-hour ambulatory double pH monitoring, VHI total scores and subscores in the emotional domains were higher in positive group than in negative group. There was no statistical difference (P>0.05) in functional and physical domains. The SF-36 scale was used to evaluate the quality of life of the patients. The difference of 6 dimensionality, scores had statistical significance (P<0.05), including role-physical, general health, validity, social function, role-emotional and mental health. There was no statistical difference in dimensionalities of role-physical and bodily pain. CONCLUSIONS: The volunteers who were diagnosed with hoarseness or dysphonia had the higher morbidity rate of LPR. At the time of treatment, more attention should be paid to the quality of life. PMID- 26888127 TI - [Significance of certain experiments relevant to airflow parameters in assessment of voice function]. AB - OBJECTIVE: To investigate the role of airflow parameters of some specific examinations in voice function assessment. METHODS: The s/z ratio, pulmonary function and phonatory aerodynamic parameters were measured in subjects with benign vocal fold lesions and with normal voice. The effect of treatment in subjects with benign vocal fold lesions was evaluated with the phonatory aerodynamic parameters. RESULTS: The value of s/z ratio in the disease group was higher than that in the normal group (P<0.05). The value of PEF was significantly different between the disease group and the normal group for male (P<0.05). MFR, MPT, PTF, SGP, PTP, VE were significantly different between the disease group and the normal group (P<0.05). MFR, MPT, PTF, SGP, PTP of the disease group after surgery for both sex were significantly different from before surgery (P<0.05). The disease group was subdivided into two groups through stroboscopic examination before and one month after surgery: the worse group (with some functional laryngeal abnormality, or organic abnormality except benign vocal fold lesion) and the better group. PTF, PTP, SGP, VE were significantly different between the worse group and the normal voice group. There was almost no significant difference for aerodynamic parameters between the better group and the normal voice group (P>0.05). There was no significant difference between the worse group after 8 weeks'voice training and the normal voice group (P>0.05). CONCLUSIONS: s/z ratio, aerodynamic parameters (MFR, MPT, SGP, PTF, PTP, VE) are valuable for the diagnosis and assessment of the voice disorders. Aerodynamic parameters are sensitive to the change of glottal function during the treatment. Voice training can increase the glottal function of patients after laryngeal microsurgery. PMID- 26888128 TI - [Experimental study on the impact of photodynamic therapy on the normal vocal cord injury]. AB - OBJECTIVE: To investigate the reactive characteristics of normal vocal cord tissues to photodynamic therapy (PDT) and the damage effects of different concentration of photosensitizer and different light on normal rabbit vocal cord. Making the preliminary research of PDT in clinical treatment of chronic inflammation of the vocal cords and precancerous lesions. METHODS: Twenty-five healthy Japanese big ear experimental rabbits were randomly divided into 5 groups: low work rate low dose group A (100 mW, 10%5-ALA), high work rate low dose group B (200 mW, 10%5-ALA), high work rate high dose group C (200 mW, 20%5 ALA), low work rate high dose group D (100 mW, 20%5-ALA) and normal control group E. The issue damage and wound recovery were observed in 1 d, 3 d, 7 d, 14 d, 28 d after intervention. RESULTS: A severe inflammation reaction was observed in group A, B, C, D after intervened with PDT compared to normal group. The reaction of group A was lighter, and the reaction of group C was the most serious. The content of collagenous fiber, hyaluronic acid and fibronectin in vocal fold lamina layer was significantly higher than that in normal group (P<0.05). Different degrees of fiber proliferation were observed in all groups. The content of each component of vocal fold lamina layer tended to be normal slightly higher level in 28 d. Observation by electron microscope showed that there were no significant differences in A, B, C, D, E in 28 d after intervention. CONCLUSION: Recoverable damage repair process can be detected in rabbit vocal after intervened with PDT, which began in 7 d and basically completed in 28 d. In a certain concentration (10%-20%) and dose range (100-200 mW). The higher of photodynamic dose, the more serious of the damage. And the damage was basically reversible. PMID- 26888129 TI - [Clinical features of sudden sensorineural hearing loss accompanied with inner ear hemorrhage]. AB - OBJECTIVE: To investigate the clinical features, diagnosis and prognosis of sudden sensorineural hearing loss accompanied with inner ear hemorrhage. METHODS: Eleven cases of sudden sensorineural hearing loss accompanied with inner ear hemorrhage were retrospectively analyzed, including clinical manifestation, hematological and audiological examinations, as well as characteristics of inner ear three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI). RESULTS: Eleven cases of sudden hearing loss with inner ear hemorrhage were accompanied by varying degrees of vertigo, lasting from several minutes to several hours, nine of whom had persistent tinnitus. The audiometry curves of the 11 cases included total deafness or flat descending type. The inner ear 3D-FLAIR MRI studies revealed abnormal high signals at different positions of the inner ear, one case with endolymphatic hydrops. After the treatment, seven cases were invalid, two cases had notable effect, and two cases were effective. CONCLUSIONS: Abnormal high signals in the inner ear were sensitively detected by 3D-FLAIR MRI sequence, which was applied for the diagnosis of the sudden hearing loss accompanied with inner ear hemorrhage. The effect of conventional treatment was not good and the appropriate treatments for this type of sudden hearing loss need further investigation. PMID- 26888130 TI - [The clinical values of VEMP in the diagnosis of vestibular nerve impairment in the patients with type 2 diabetes mellitus]. AB - OBJECTIVE: To explore the values of vestibular evoked myogenic potential (VEMP) in the diagnosis of vestibular nerve impairment in type 2 diabetes mellitus patients. METHODS: Forty-two cases (84 ears) of diabetes mellitus patients and 42 cases (84 ears) normal subjects as the control group were enrolled from 2014 to 2015.Both the patients and normal subjects underwent conventional air-conducted ocular vestibular evoked myogenic potential (oVEMP) and cervical vestibular evoked myogenic potential (cVEMP) in bilateral ears.The results were compared between the patients and normal subjects. A commercially available software package, SPSS19.0, was used for statistical analysis. RESULTS: In 84 ears of the normal subjects, oVEMP was present in 70 ears, the educible rate was 83.3% (70/84). cVEMP was present in 74 ears, and the educible rate was 88.1% (74/84). In 84 ears of the diabetes mellitus patients, oVEMP was present in 49 ears, with the educible rate of 58.3% (49/84). cVEMP was present in 52 ears, with the educible rate of 61.9% (52/84). The educible rate in the control group was significantly higher than the diabetic group (oVEMP: chi(2)=12.71, P<0.05; cVEMP: chi(2)=15.37, P<0.05). In the diabetic group, the mean values of both oVEMP and cVEMP P1, N1 latencies were significantly longer when compared to the control group (P<0.05). No significantly statistical difference was found in oVEMP and cVEMP parameters (threshold, latency interval and amplitude) between groups (P>0.05). CONCLUSIONS: Vestibular nerve was impaired in diabetes mellitus patients in some degree. VEMP examinations could be useful in the diagnosis of vestibular nerve impairment in type 2 diabetes mellitus patients. PMID- 26888132 TI - [Expression and prognostic value of MTDH, Bcl-2 and E-cadherin in sinonasal malignant mucosal melanoma]. AB - OBJECTIVE: To study the expression and predictive value of MTDH, Bcl-2 and E cadherin in sinonasal malignant mucosal melanoma (SNM). METHODS: Seventy-four formalin-fixed paraffin-embedded SNM specimens were subjected to immunohistochemical staining of MTDH, Bcl-2 and E-cadherin. Correlation between staining results and disease outcome was analyzed.SPSS 19.0 software was used to analyze the data. RESULTS: Positive staining of MTDH, Bcl-2 and E-cadherin was observed in 56/74 (75.7%), 18/74 (24.3%) and 21/74 (28.4%) cases, respectively. MTDH positive patients had higher metastatic rate than MTDH negative patients (67.9% vs. 33.3%, P=0.009, OR=2.037, 95% CI: 1.034-4.016). Negative Bcl-2 was correlated with worse overall survival time (HR=2.023, P=0.025). Expression of E cadherin was adversely associated with expression of MTDH (r=-0.315, P=0.006). CONCLUSION: High MTDH expression and low Bcl-2 expression suggest poor prognosis of SNM, while the predictive value of E-cadherin needs further study. PMID- 26888131 TI - [Clinical analysis of sphenoid sinusitis after transsphenoidal sellar surgery]. AB - OBJECTIVE: To analyze the possible influence factors of sphenoid sinusitis after endoscopic transsphenoidal sellar surgery. METHODS: A retrospective analysis of 177 patients who underwent transsphenoidal sellar surgery, from January 2009 to January 2014 in Tianjin Huanhu Hospital was performed. All patients were followed up with nasal endoscope. The risk factors of sphenoid sinusitis after surgery were analyzed statistically, such as sex, age, categories of disease, surgical produres, tumor size, using artificial or self material repair, with or without EC glue intraoperatively, etc. SPSS 17.0 software was used to analyze the data. RESULTS: After surgery, there were 34 (19.2%) patients developed postoperative sinusitis. EC glue was the sole risk factor for postoperative sinusitis (34.57% vs 6.25%, chi(2)=22.701, P<0.01), but the sex, age, categories of disease, surgical produres, tumor size and patching material had no significant difference (all P>0.05). CONCLUSIONS: In patients with endoscopic transsphenoidal sellar surgery, regular postoperative nasal endoscopic follow-up found that the use of EC glue was the risk factor for the development of postoperative sphenoid sinusitis. PMID- 26888133 TI - [The study of acoustically evoked short latency negative responses in normal guinea pigs]. AB - OBJECTIVE: To compare acoustically evoked short latency negative responses (ASNR) elicited from normal and profound hearing loss guinea pig ears and to confirm their vestibular nuclei origination. METHODS: Forty healthy guinea pigs were employed in the experiment, which were randomly divided into the control group (8 subjects, 16 ears), the masking group (16 subjects, 32 ears) and the deafened group (16 subjects, 32 ears). Air conductive white noise was chosen for masking. Masking dilemma was avoidable by an appropriate 15 dB gap between stimulus and masking sound. Both the masking group and the deafened group were further divided into ASNR group and non-ASNR group based on the presence of ASNR. Electrolytic lesion was conducted to the vestibular nuclei, followed by ABR/ASNR recording. The lesioned brainstem slices were microscopically verified. RESULTS: In the masking group, ASNR were present in 24 ears (75.0%, 24/32) and 12 ears (46.2%, 12/26) in deafened group, showing statistically higher presence rate for masking group (chi(2)=5.07, P=0.024). There were no significant differences for the ASNR threshold and latency between the masking ASNR group and the deafened ASNR group. For the two ASNR groups, electrolytic destruction to the vestibular nuclei subsequently eliminated the ASNR. Brainstem slice proved the accurate sites of electrolytic lesion. CONCLUSION: Moderate white noise masking prevents hearing system potential overlap without affecting vestibular system, therefore, ASNR is successfully elicited in normal guinea pigs. Both ASNRs from normal and deafened guinea pigs are of similar natures and origination from, the vestibular nuclei. PMID- 26888134 TI - [The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism]. AB - OBJECTIVE: To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. METHOD: Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 ug/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. RESULT: The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 ug/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (P<0.05). The levels of urinary calcium and serum BALP in rats of maximum rPTH(1-84) injection group (160 ug/kg) were higher than those of normal control group (P<0.05). The rats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus concentration compared with normal control group (P<0.05). The amount of urinary calcium also exceeded the other groups (P<0.05), but no with significant difference in BMD of bilateral femoral bone and lumbar vertebra between negative control group and normal control group (P>0.05). CONCLUSION: Calcium and phosphorus return to normal level by administration of rPTH(1-84) in the dose of 80 ug/kg or 160 ug/kg, with increase in BMD. Calcitriol can return the level of calcium to normal and increase BMD, but can not correspondingly decrease the phosphorus concentration and increase the excretion of calcium in urine. PMID- 26888136 TI - [Cochlear implantation in human immunodeficiency virus-infected patients]. PMID- 26888137 TI - [Observation of 68 cases of auricular pseudo cyst treated with suture and compression bandage]. PMID- 26888135 TI - [Transplantation of free latissimus dorsimyocutaneous flaps for repairing head and neck defect after tumor resection]. AB - OBJECTIVE: To explore the value of free latissimus dorsimyocutaneous flap in repairing severe defect of head and neck after resection of tumor. METHODS: Free latissimus dorsimyocutaneous flap was used to repair defect after resection of tumor in 12 patients (13 sides) with head and neck tumors. Of them 2 cases underwent radical radiotherapy before operation. and 3 cases received adjuvant radiotherapy postoperatively. RESULTS: Aside from one flap with necrosis, other 12 flaps survived after operation including 5 cases with radiotherapy. CONCLUSION: Free latissimus dorsimyocutaneous flap can afford large tissue, has reliable blood supply, is easy to survive, and resist to radiotherapy, which is fit for repairing severe defect of head and neck. PMID- 26888138 TI - [Comparison of post-operation effect of nasal septal sutures and nasal packing in septoplasty]. PMID- 26888139 TI - [Observation of curative effcet on glottic cancer via minimally invasive surgery by PMOD: report of 12 cases]. PMID- 26888140 TI - [Low grade fibromyxoid sarcoma in infant and the clinical review]. PMID- 26888141 TI - [Lipoma of the cervical esophagus: a case report]. PMID- 26888142 TI - [Minutes of the 15th International Thyroid Congress]. PMID- 26888143 TI - [The value of intraoperative Parathyroid Hormone Monitoring for secondary hyperparathyroidism]. PMID- 26888144 TI - [Diagnosis and treatment of laryngeal leukoplakia]. PMID- 26888145 TI - [Behavioral treatment of glottal incompetence]. PMID- 26888146 TI - Novel markers to detect recombinant human insulin-like growth factor-I (rhIGF I)/rhIGF binding protein-3 (rhIGFBP-3) misuse in athletes. AB - Insulin-like growth factor-I (IGF-I) is abused by elite athletes for its metabolic and anabolic effects. We have previously shown that it is possible to detect IGF-I misuse by measuring serum IGF-I and procollagen type III amino terminal propeptide (P-III-NP) but a pilot study suggested measuring IGF-II, IGF binding protein-2 (IGFBP-2) and acid-labile subunit (ALS) may improve the detection of IGF-I administration. The aim of the study was to assess this in a randomized controlled trial. Twenty-six female and 30 male recreational athletes were randomized to 28 days' treatment with placebo or recombinant human (rh)IGF I/rhIGF binding protein-3 (IGFBP-3) complex (30 mg/day or 60 mg/day), followed by 56 days' washout. IGF-II, IGFBP-2 and ALS (women only) were measured using commercial immunoassays. IGFBP-2 increased and IGF-II decreased in response to both low and high dose rhIGF-I/rhIGFBP-3 in both women and men while ALS decreased in women in response to high dose rhIGF-I/rhIGFBP-3. Two days after discontinuing treatment, significant differences remained between the three treatment groups in IGFBP-2 and IGF-II, but not ALS. Thereafter there were no significant differences between the three treatment groups in any of the markers. Combining IGF-I with IGF-II and/or IGFBP-2 improved the performance of the test to detect rhIGF-I/rhIGFBP-3 administration in both women and men. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888147 TI - Semimetallization of dielectrics in strong optical fields. AB - At the heart of ever growing demands for faster signal processing is ultrafast charge transport and control by electromagnetic fields in semiconductors. Intense optical fields have opened fascinating avenues for new phenomena and applications in solids. Because the period of optical fields is on the order of a femtosecond, the current switching and its control by an optical field may pave a way to petahertz optoelectronic devices. Lately, a reversible semimetallization in fused silica on a femtosecond time scale by using a few-cycle strong field (~1 V/A) is manifested. The strong Wannier-Stark localization and Zener-type tunneling were expected to drive this ultrafast semimetallization. Wider spread of this technology demands better understanding of whether the strong field behavior is universally similar for different dielectrics. Here we employ a carrier-envelope phase stabilized, few-cycle strong optical field to drive the semimetallization in sapphire, calcium fluoride and quartz and to compare this phenomenon and show its remarkable similarity between them. The similarity in response of these materials, despite the distinguishable differences in their physical properties, suggests the universality of the physical picture explained by the localization of Wannier-Stark states. Our results may blaze a trail to PHz-rate optoelectronics. PMID- 26888148 TI - Combination of Urinary Biomarkers Improves Early Detection of Acute Kidney Injury in Patients With Heart Failure. AB - BACKGROUND: Acute kidney injury (AKI) is associated with morality and repeated hospitalization, and is frequently encountered in patients with acute decompensated heart failure (ADHF). However, few effective tools exist for early AKI identification and risk stratification. METHODS AND RESULTS: This was a prospective observational study conducted in the coronary care unit (CCU) of a tertiary care university hospital. Patients with a diagnosis of ADHF and who were using diuretics were enrolled.Samples collected between December 2013 and February 2015 were tested for serum cystatin C (Cys-C), urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Demographic, clinical, and laboratory data were evaluated. A total of 103 adult patients with a mean age of 68 years were investigated. AKI was diagnosed in 49 patients (47.6%). For predicting intrinsic AKI on the first day of CCU admission, a combination of Cys-C and urine KIM-1 yielded an excellent area under the receiver operating characteristic curve of 0.828, a sensitivity of 71.0%, and specificity of 43.0%, for an overall accuracy of 78%. CONCLUSIONS: In this study, we found that combinations of the biomarker (Cys-C and KIM-1) were an effective clinical model for predicting AKI in patients with ADHF. The biomarker was also useful for differentiating subclinical AKI in patients with ADHF. PMID- 26888149 TI - Edoxaban vs. Warfarin in East Asian Patients With Atrial Fibrillation - An ENGAGE AF-TIMI 48 Subanalysis. AB - BACKGROUND: In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia. METHODS AND RESULTS: Patients aged >=21 years with documented AF and CHADS score >=2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0-3.0. Patients with a creatinine clearance of 30-50 ml/min, weighing <=60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31-0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63-1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41-0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21-0.54, P<0.001). CONCLUSIONS: Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population. PMID- 26888150 TI - Coagulation-Fibrinolysis System and Postoperative Outcomes of Patients With Chronic Thromboembolic Pulmonary Hypertension. AB - BACKGROUND: The postoperative changes in the coagulation-fibrinolysis system and the association between the system and postoperative course of patients with chronic thromboembolic pulmonary hypertension (CTEPH) who have undergone pulmonary endarterectomy (PEA) remain unclear. METHODS AND RESULTS: Between 1986 and 2013, 117 patients (55.1+/-11.2 years, preoperative mean pulmonary arterial pressure 46.5+/-10.5 mmHg) underwent PEA, and 15 patients died during the perioperative period. We studied the association between the preoperative coagulation-fibrinolysis markers and surgical outcomes of all patients, and the long-term outcomes of the 102 survivors from the date of PEA. We also investigated the postoperative changes in coagulation-fibrinolysis markers and their association with residual pulmonary hypertension (PH) in 20 consecutive patients. Only an elevated factor VIII level was associated with perioperative death. Thrombomodulin and plasminogen values were significantly increased after PEA. Univariate logistic regression analysis revealed that D-dimer positivity at follow-up was a risk factor for residual PH. Patients with both an elevated fibrinogen level (>=291 mg/dl [median]) and decreased plasminogen activity (<100% [median]) had significantly worse disease-specific survival than the other patients (5-year disease-specific survival: 84.0% vs. 100%, respectively; P=0.0041 [log-rank test]). CONCLUSIONS: Preoperatively high fibrinogen and low plasminogen values in patients with CTEPH are associated with poor long-term postoperative outcome. PEA benefited not only the pulmonary hemodynamics but also the coagulation-fibrinolysis system of patients. PMID- 26888151 TI - Band engineering and improved thermoelectric performance in M-doped SnTe (M = Mg, Mn, Cd, and Hg). AB - The electronic structures of M-doped SnTe (M = Mg, Mn, Cd, and Hg) are investigated by using first-principles calculations including spin-orbit coupling. It is found that Sn vacancy plays an important role in the band engineering of SnTe, showing a different property from its related compound PbTe. The enlarged band gap and reduced energy separation between two valence bands are in good agreement with experimental measurements. Both of the two band modifications lead to the increase of Seebeck coefficients, which is explicitly confirmed by the followed Boltzmann transport calculations. The calculated Seebeck coefficients for Mn-doped SnTe agree well with the experimental data in a broad range of carrier concentration. Owing to the improved Seebeck coefficients, Mn- and Cd-doped SnTe exhibit promising thermoelectric properties with ZT = 1.32 and 1.65 at around 800 K, respectively. PMID- 26888152 TI - Facile fabrication of rice husk based silicon dioxide nanospheres loaded with silver nanoparticles as a rice antibacterial agent. AB - Bacterial leaf blight of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is a major disease of rice, leading to reduction in production by 10-50%. In order to control this disease, various chemical bactericides have been used. Wide and prolonged application of chemical bactericides resulted in the resistant strain of Xoo that was isolated from rice. To address this problem, we were searching for an environmentally friendly alternative to the commonly used chemical bactericides. In this work, we demonstrate that silicon dioxide nanospheres loaded with silver nanoparticles (SiO2-Ag) can be prepared by using rice husk as base material precursor. The results of the antibacterial tests showed that SiO2 Ag composites displayed antibacterial activity against Xoo. At cellular level, the cell wall/membrane was damaged and intercellular contents were leaked out by slow-releasing of silver ions from SiO2-Ag composites. At molecular level, this composite induced reactive oxygen species production and inhibited DNA replication. Based on the results above, we proposed the potential antibacterial mechanism of SiO2-Ag composites. Moreover, the cytotoxicity assay indicated that the composites showed mild toxicity with rice cells. Thus, this work provided a new strategy to develop biocide derived from residual biomass. PMID- 26888154 TI - Modulation of mitochondrial ion transport by inorganic polyphosphate - essential role in mitochondrial permeability transition pore. AB - Inorganic polyphosphate (polyP) is a biopolymer of phosphoanhydride-linked orthophosphate residues. PolyP is involved in multiple cellular processes including mitochondrial metabolism and cell death. We used artificial membranes and isolated mitochondria to investigate the role of the polyP in mitochondrial ion transport and in activation of PTP. Here, we found that polyP can modify ion permeability of de-energised mitochondrial membranes but not artificial membranes. This permeability was selective for Ba2+ and Ca2+ but not for other monovalent and bivalent cations and can be blocked by inhibitors of the permeability transition pore - cyclosporine A or ADP. Lower concentrations of polyP modulate calcium dependent permeability transition pore opening. Increase in polyP concentrations and elongation chain length of the polymer causes calcium independent swelling in energized conditions. Physiologically relevant concentrations of inorganic polyP can regulate calcium dependent as well calcium independent mitochondrial permeability transition pore opening. This raises the possibility that cytoplasmic polyP can be an important contributor towards regulation of the cell death. PMID- 26888153 TI - Impact of food supplementation on weight loss in randomised-controlled dietary intervention trials: a systematic review and meta-analysis. AB - Dietary trials provide evidence for practice and policy guidelines, but poor adherence may confound results. Food supplementation may improve adherence to dietary interventions, but the impact of supplementation on study outcomes is not known. The aim of this review was to examine the impact of food supplementation on weight loss in dietary intervention trials. The databases Scopus, PubMed and the Cochrane Library were searched for dietary intervention trials published between January 2004 and March 2015 using the following keyword combinations: 'trial' OR 'intervention', 'food' OR 'diet', 'weight loss' and 'adherence' OR 'adherence'. Studies were included if food was provided to at least one study group and both 'weight change' and 'adherence' were reported. Random effects meta analyses were conducted to assess weighted mean differences (WMD) in body weight (change or final mean values). The included studies formed two groups: trials involving an intervention group supplemented with a food and a control without food supplementation (food v. no food), and trials in which food was provided to all subjects (food v. food) (PROSPERO registration: CRD42015017563). In total, sixteen studies were included. Significant weight reduction was reported in the food v. no food studies (WMD -0.74 kg; 95 % CI -1.40, -0.08; P=0.03, I 2=63 %). A non-significant increase in weight was found among the food v. food studies (WMD 0.84 kg; 95 % CI -0.60, 2.27; P=0.25, I 2=0 %). Food supplementation appeared to result in greater weight loss in dietary trials. Energy restrictions and intensity of interventions were other significant factors influencing weight loss. PMID- 26888155 TI - Soapbox: Class matters in parenting interventions. AB - Class and income level influence parenting styles and values, yet are rarely discussed in treatment approaches and parenting interventions with families. In this soapbox article, I argue that discrepancies in outcome, retention, and participation could be fruitfully addressed through a fuller understanding of the needs, realities, and parenting goals of families struggling with financial disadvantage. I compare and contrast ethnographic studies of parenting in low socioeconomic environments with the types of strategies and interventions commonly advanced in parent training programs and suggest that clinicians must become more aware of the cultural and socioeconomic overtones of those interventions in determining whether, how, and when to use them with families. PMID- 26888156 TI - Microarray analysis of transcripts with elevated expressions in the rat medial or lateral habenula suggest fast GABAergic excitation in the medial habenula and habenular involvement in the regulation of feeding and energy balance. AB - In vertebrates the "anti-reward-system" mainly is represented by the habenula and its medial (MHb) and especially lateral (LHb) complexes. Considerable knowledge has accumulated concerning subnuclear structures and connectivities of MHb and LHb subnuclei. The present investigation aimed to obtain novel information, whether MHb or LHb or their subnuclei display field-characteristic gene products, which may shed light on biological functions of these areas. Unfortunately this was not the case. Microarray analysis of mRNAs in microdissected habenular and thalamic control areas yielded expression values of 17,745 RNAs representing protein-coding genes, to which annotated gene names could be assigned. High relative values of genes with known expression in MHb, LHb or thalamus in the corresponding areas indicated a high precision of the microdissection procedure. Note that the present report emphasizes differences between and not absolute expression values in the selected regions. The present investigation disclosed that the LHb genetically is much closer related to the thalamus as compared to the MHb. The results presented here focuse on gene transcripts related to major transmitter systems, catecholamines and neuropeptides. Quite surprisingly, our data indicate potentially inhibitory effects of acetylcholine and glutamate in the habenula. In addition, the absence of the K-Cl co-transporter 2 supports a largely excitatory role of GABAergic transmission especially in the MHb. Furthermore, several G-protein related receptors (Gpr83, Gpr139, Gpr149, Gpr151, Gpr158) and many neuropeptides related to feeding are differentially expressed in the habenular region, indicating that its involvement in the regulation of food consumption and energy expenditure may have been underestimated so far. PMID- 26888157 TI - Impact of host sex and group composition on parasite dynamics in experimental populations. AB - To better understand the spread of disease in nature, it is fundamentally important to have broadly applicable model systems with readily available species which can be replicated and controlled in the laboratory. Here we used an experimental model system of fish hosts and monogenean parasites to determine whether host sex, group size and group composition (single-sex or mixed-sex) influenced host-parasite dynamics at an individual and group level. Parasite populations reached higher densities and persisted longer in groups of fish compared with isolated hosts and reached higher densities on isolated females than on isolated males. However, individual fish within groups had similar burdens to isolated males regardless of sex, indicating that females may benefit more than males by being in a group. Relative condition was positively associated with high parasite loads for isolated males, but not for isolated females or grouped fish. No difference in parasite dynamics between mixed-sex groups and single-sex groups was detected. Overall, these findings suggest that while host sex influences dynamics on isolated fish, individual fish in groups have similar parasite burdens, regardless of sex. We believe our experimental results contribute to a mechanistic understanding of host-parasite dynamics, although we are cautious about directly extrapolating these results to other systems. PMID- 26888160 TI - CAN HALF VALUE LAYER MEASUREMENTS BE USED TOGETHER WITH THE EFFECTIVE ENERGY TO OBTAIN CONVERSION COEFFICIENTS FOR X-RAY SPECTRA? AB - Conversion coefficients are a substantial vehicle in practical radiation protection to determine the dose (rate) of a given radiation field. According to ICRU report 57, their values shall be obtained by means of spectrometry. This is, however, a time-consuming complicated procedure that cannot be performed by all dosimetry laboratories. Therefore, it is desired to find acceptable alternative methods to replace spectrometry. One possibility is to set up the X-ray facility in accordance with international standard ISO 4037-1:1997 and use the tabulated values from that standard. However, this needs to be considered during the construction phase of the X-ray facility. In this work, the combined usage of half-value layer measurements and the effective energy (both with respect to air kerma) to determine the conversion coefficients is investigated and compared with the values obtained by spectrometry. The investigations utilise all combinations of the H-, W-, N- and L-series, reference distances of 1 and 2.5 m and aluminium and copper as attenuation materials. We find that for most of the radiation qualities, the investigated method results in conversion coefficients that show an unacceptable deviation from the conventionally true values. However, the values of conversion coefficients of selected N- and L-qualities could be reproduced with high accuracy (within +/-1 %). PMID- 26888159 TI - Sulphur Kbeta emission spectra reveal protonation states of aqueous sulfuric acid. AB - In this paper we report an X-ray emission study of bulk aqueous sulfuric acid. Throughout the range of molarities from 1 M to 18 M the sulfur Kbeta emission spectra from H2SO4 (aq) depend on the molar fractions and related deprotonation of H2SO4. We compare the experimental results with results from emission spectrum calculations based on atomic structures of single molecules and structures from ab initio molecular dynamics simulations. We show that the S Kbeta emission spectrum is a sensitive probe of the protonation state of the acid molecules. Using non-negative matrix factorization we are able to extract the fractions of different protonation states in the spectra, and the results are in good agreement with the simulation for the higher part of the concentration range. PMID- 26888158 TI - Comparative mRNA analysis of behavioral and genetic mouse models of aggression. AB - Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression-related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of aggression with those from a recent genetic mouse model aggression. The study used a discovery-replication design using two independent mRNA studies from mouse brain tissue. The discovery study identified strain (BALB/cJ and C57BL/6J) * stress (chronic mild stress or control) interactions. Probe sets differentially regulated in the discovery set were intersected with those uncovered in the replication study, which evaluated differences between high and low aggressive animals from three strains specifically bred to study aggression. Network analysis was conducted on overlapping genes uncovered across both studies. A significant overlap was found with the genetic mouse study sharing 1,916 probe sets with the stress model. Fifty-one probe sets were found to be strongly dysregulated across both studies mapping to 50 known genes. Network analysis revealed two plausible pathways including one centered on the UBC gene hub which encodes ubiquitin, a protein well-known for protein degradation, and another on P38 MAPK. Findings from this study support the stress model of aggression, which showed remarkable molecular overlap with a genetic model. The study uncovered a set of candidate genes including the Erg2 gene, which has previously been implicated in different psychopathologies. The gene networks uncovered points at a Redox pathway as potentially being implicated in aggressive related behaviors. PMID- 26888161 TI - Prediction of clinical and endoscopic responses to anti-tumor necrosis factor alpha antibodies in ulcerative colitis. AB - Objective In patients with ulcerative colitis (UC), the relationship between the initial endoscopic findings and the response to anti-tumor necrosis factor (TNF) alpha antibodies remains unclear. We herein evaluated the potential of endoscopic assessment using the ulcerative colitis endoscopic index of severity (UCEIS) to predict the response to anti-TNF-alpha antibodies. Methods We enrolled 64 patients with UC undergoing anti-TNF-alpha maintenance therapy with infliximab (IFX) or adalimumab (ADA) between April 2010 and March 2015. Anti-TNF-alpha trough levels were determined by ELISA. Endoscopic disease activity was assessed using the UCEIS. Results The clinical response rate at 8 weeks was 77.4% for IFX and 66.7% for ADA. Serum albumin levels were significantly higher and the UCEIS bleeding descriptor before treatment was significantly lower in the responders than in the non-responders (p < 0.05 each). The CRP levels at 2 weeks were significantly lower in the responders (p < 0.001). The serum albumin levels before treatment were significantly higher and the UCEIS erosions and ulcers descriptor was significantly lower in the mucosal healing group than in the non mucosal healing group (p < 0.05 each). A significant and negative correlation between the trough levels of anti-TNF-alpha antibodies and the UCEIS descriptors was observed. The trough levels of anti-TNF-alpha antibodies to achieve mucosal healing were 2.7 MUg/mL for IFX and 10.3 MUg/mL for ADA. Conclusions The UCEIS score, as well as some clinical markers (serum albumin and CRP levels), is useful for the prediction of the treatment outcome of UC patients in response to anti TNF-alpha antibodies. PMID- 26888162 TI - Regional T1 relaxation time constants in Ex vivo human brain: Longitudinal effects of formalin exposure. AB - PURPOSE: Relaxation time constants are useful as markers of tissue properties. Imaging ex vivo tissue is done for research purposes; however, T1 relaxation time constants are altered by tissue fixation in a time-dependent manner. This study investigates regional changes in T1 relaxation time constants in ex vivo brain tissue over 6 months of fixation. METHODS: Five ex vivo human brain hemispheres in 10% formalin were scanned over 6 months. Mean T1 relaxation time constants were measured in regions of interest (ROIs) representing gray matter (GM) and white matter (WM) regions and analyzed as a function of fixation time. RESULTS: Cortical GM ROIs had longer T1 relaxation time constants than WM ROIs; the thalamus had T1 relaxation time constants similar to those of WM ROIs. T1 relaxation time constants showed rapid shortening within the first 6 weeks after fixation followed by a slower rate of decline. CONCLUSION: Both GM and WM T1 relaxation time constants of fixed brain tissue show rapid decline within the first 6 weeks after autopsy and slow by 6 months. This information is useful for optimizing MR imaging acquisition parameters according to fixation time for ex vivo brain imaging studies. Magn Reson Med 77:774-778, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. PMID- 26888164 TI - Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion. AB - AIM: To evaluate the effects of the primary human bile acid, chenodeoxycholic acid (CDCA), and the bile acid sequestrant (BAS) colesevelam, instilled into the stomach, on plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide, glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin, as well as on gastric emptying, gallbladder volume, appetite and food intake. METHODS: On four separate days, nine patients with type 2 diabetes, and 10 matched healthy control subjects received bolus instillations of (i) CDCA, (ii) colesevelam, (iii) CDCA + colesevelam or (iv) placebo. At baseline and for 180 min after instillation, blood was sampled. RESULTS: In both the type 2 diabetes group and the healthy control group, CDCA elicited an increase in GLP-1 levels compared with colesevelam, CDCA + colesevelam and placebo, respectively (p < 0.05). The interventions did not affect plasma glucose, insulin or C-peptide concentrations in any of the groups. CDCA elicited a small increase in plasma insulin : glucose ratio compared with colesevelam, CDCA + colesevelam and placebo in both groups. Compared with colesevelam, CDCA + colesevelam and placebo, respectively, CDCA increased glucagon and delayed gastric emptying in both groups. CONCLUSIONS: CDCA increased GLP-1 and glucagon secretion, and delayed gastric emptying. We speculate that bile acid-induced activation of TGR5 on L cells increases GLP-1 secretion, which, in turn, may result in amplification of glucose-stimulated insulin secretion. Furthermore our data suggest that colesevelam does not have an acute effect on GLP-1 secretion in humans. PMID- 26888165 TI - Information-Theoretic Measures Predict the Human Judgment of Rhythm Complexity. AB - To formalize the human judgment of rhythm complexity, we used five measures from information theory and algorithmic complexity to measure the complexity of 48 artificially generated rhythmic sequences. We compared these measurements to human prediction accuracy and easiness judgments obtained from a listening experiment, in which 32 participants guessed the last beat of each sequence. We also investigated the modulating effects of musical expertise and general pattern identification ability. Entropy rate and Kolmogorov complexity were correlated with prediction accuracy, and highly correlated with easiness judgments. A logistic regression showed main effects of musical training, entropy rate, and Kolmogorov complexity, and an interaction between musical training and both entropy rate and Kolmogorov complexity. These results indicate that information theoretic concepts capture some salient features of the human judgment of rhythm complexity, and they confirm the influence of musical expertise on complexity judgments. PMID- 26888163 TI - Distinct activation of primary human BDCA1(+) dendritic cells upon interaction with stressed or infected beta cells. AB - Derailment of immune responses can lead to autoimmune type 1 diabetes, and this can be accelerated or even induced by local stress caused by inflammation or infection. Dendritic cells (DCs) shape both innate and adaptive immune responses. Here, we report on the responses of naturally occurring human myeloid BDCA1(+) DCs towards differentially stressed pancreatic beta cells. Our data show that BDCA1(+) DCs in human pancreas-draining lymph node (pdLN) suspensions and blood derived BDCA1(+) DCs both effectively engulf beta cells, thus mimicking physiological conditions. Upon uptake of enterovirus-infected, but not mock infected cells, BDCA1(+) DCs induced interferon (IFN)-alpha/beta responses, co stimulatory molecules and proinflammatory cytokines and chemokines. Notably, induction of stress in beta cells by ultraviolet irradiation, culture in serum free medium or cytokine-induced stress did not provoke strong DC activation, despite efficient phagocytosis. DC activation correlated with the amount of virus used to infect beta cells and required RNA within virally infected cells. DCs encountering enterovirus-infected beta cells, but not those incubated with mock infected or stressed beta cells, suppressed T helper type 2 (Th2) cytokines and variably induced IFN-gamma in allogeneic mixed lymphocyte reaction (MLR). Thus, stressed beta cells have little effect on human BDCA1(+) DC activation and function, while enterovirus-infected beta cells impact these cells significantly, which could help to explain their role in development of autoimmune diabetes in individuals at risk. PMID- 26888166 TI - Identification, Recombinant Expression, and Biochemical Analysis of Putative Secondary Product Glucosyltransferases from Citrus paradisi. AB - Flavonoid and limonoid glycosides influence taste properties as well as marketability of Citrus fruit and products, particularly grapefruit. In this work, nine grapefruit putative natural product glucosyltransferases (PGTs) were resolved by either using degenerate primers against the semiconserved PSPG box motif, SMART-RACE RT-PCR, and primer walking to full-length coding regions; screening a directionally cloned young grapefruit leaf EST library; designing primers against sequences from other Citrus species; or identifying PGTs from Citrus contigs in the harvEST database. The PGT proteins associated with the identified full-length coding regions were recombinantly expressed in Escherichia coli and/or Pichia pastoris and then tested for activity with a suite of substrates including flavonoid, simple phenolic, coumarin, and/or limonoid compounds. A number of these compounds were eliminated from the predicted and/or potential substrate pool for the identified PGTs. Enzyme activity was detected in some instances with quercetin and catechol glucosyltransferase activities having been identified. PMID- 26888167 TI - Estradiol modulates Na(+) -dependent HCO3 (-) transporters altering intracellular pH and ion transport in human Sertoli cells: A role on male fertility? AB - BACKGROUND INFORMATION: Infertile men often present deregulation of serum estrogen levels. Notably, high levels of estradiol (E2) are associated with low sperm production and quality. Sertoli cells (SCs) are responsible for spermatogenesis maintenance and are major targets for the hormonal signalling that regulates this complex process. RESULTS: In this study, we used primary cultures of human SCs and studied the localisation, expression and functionality of the Na(+) -dependent HCO3 (-) transporters by confocal microscopy, immunoblot, epifluorescence and voltage clamp after 24 h of exposure to E2 (100 nM). All studied transporters were identified in human SCs. In E2-treated human SCs, there was an increase in NBCn1, NBCe1 and NDCBE protein levels, as well as an increase in intracellular pH and a decrease in transcellular transport. CONCLUSIONS: We report an association between increased levels of E2 and the expression/function of Na(+) -dependent HCO3 (-) transporters in human SCs. Our results provide new evidence on the mechanisms by which E2 can regulate SCs physiology and consequently spermatogenesis. These mechanisms may have an influence on male reproductive potential and help to explain male infertility conditions associated with estrogen deregulation. SIGNIFICANCE: Exposure to E2 increased human SCs intracellular pH. E2 is a modulator of ionic transcellular transport in human SCs. PMID- 26888168 TI - Arrhythmias: IL-6 and risk of atrial fibrillation in chronic kidney disease. PMID- 26888170 TI - Vascular disease: Vorapaxar for the treatment of PAD. PMID- 26888171 TI - A ratiometric fluorescent formaldehyde probe for bioimaging applications. AB - We have described a ratiometric fluorescent formaldehyde probe (RFFP) based on the 6-hydroxy naphthalene chromophore for the first time. The probe is suitable for ratiometric detection of formaldehyde both in the solution and living biological samples with two distinct emission bands. PMID- 26888172 TI - Nanostructuration Effect on the Thermal Behavior of Ionic Liquids. AB - This work shows how the nanostructuration of ionic liquids (ILs) governs the glass and melting transitions of the bistriflimide imidazolium-based [Cn C1 im][NTf2 ] and [Cn Cn im][NTf2 ] series, which highlights the trend shift that occurs at the critical alkyl size (CAS) of n=6. An initial increase in the glass temperature (Tg ) with an increase in the alkyl side chain was observed due to the intensification of the dispersive interactions (van der Waals). Above the CAS, the -CH2 - increment has the same effect in both glass and liquid states, which leads to a plateau in the glass transition after nanostructuration. The melting temperature (Tm ) of the [Cn C1 im][NTf2 ] and [Cn Cn im][NTf2 ] series presents a V-shaped profile. For the short-alkyl ILs, the -CH2 - increment affects the electrostatic ion pair interactions, which leads to an increase in the conformational entropy. The -CH2 - increment disturbs the packing ability of the ILs and leads to a higher entropy value (DeltaslSm? ) and consequently a decrease in Tm . Above the CAS, the -CH2 - contribution to the melting temperature becomes more regular, as a consequence of the nanostructuration of the IL into polar and nonpolar domains. The dependence of the alkyl chain on the temperature, enthalpy, and entropy of melting in the ILs above the CAS is very similar to the one observed for the alkane series, which highlights the importance of the nonpolar alkyl domains on the ILs thermal behavior. PMID- 26888173 TI - Effect of laser preparation on adhesion of a self-adhesive flowable composite resin to primary teeth. AB - The aim of the study was to evaluate the adhesion of a self-adhering flowable composite resin to primary tooth enamel and dentin after silicon carbide paper (SiC) and laser pretreatment. Adhesive properties were evaluated as shear bond strength (SBS) and scanning electron microscopic (SEM) characteristics. A total 120 primary canine teeth were randomly divided into two groups to study enamel and dentin. Each group was divided into 6 subgroups (n = 10) according to type of surface preparation (SiC or Er:YAG laser) of enamel or dentin. Three methods were used to build cylinders of restoration on tooth surface: OptiBond All-In-One + Premise Flowable composite, OptiBond All-In-One + Vertise Flow and Vertise flow. After restoration, samples were tested for SBS and failure mode. Twenty eight samples were examined by SEM. The results of the study showed SBS of Vertise Flow was lower than others in enamel and dentin samples pretreated with SiC and in dentin samples pretreated with laser (P < 0.001). Compared to SiC pretreatment, laser pretreatment led to a significantly higher SBS with Vertise Flow on enamel (P < 0.001). Vertise Flow associated with the adhesive led to a higher SBS in enamel and dentin compared to Vertise Flow alone. Adhesive and mixed failure modes were observed more frequently in Vertise Flow groups. SEM images showed that Vertise Flow led to more irregularities on enamel and more open dentinal tubules after laser ablation compared SiC pretreatment. PMID- 26888174 TI - Recurrent Spiking Networks Solve Planning Tasks. AB - A recurrent spiking neural network is proposed that implements planning as probabilistic inference for finite and infinite horizon tasks. The architecture splits this problem into two parts: The stochastic transient firing of the network embodies the dynamics of the planning task. With appropriate injected input this dynamics is shaped to generate high-reward state trajectories. A general class of reward-modulated plasticity rules for these afferent synapses is presented. The updates optimize the likelihood of getting a reward through a variant of an Expectation Maximization algorithm and learning is guaranteed to convergence to a local maximum. We find that the network dynamics are qualitatively similar to transient firing patterns during planning and foraging in the hippocampus of awake behaving rats. The model extends classical attractor models and provides a testable prediction on identifying modulating contextual information. In a real robot arm reaching and obstacle avoidance task the ability to represent multiple task solutions is investigated. The neural planning method with its local update rules provides the basis for future neuromorphic hardware implementations with promising potentials like large data processing abilities and early initiation of strategies to avoid dangerous situations in robot co worker scenarios. PMID- 26888175 TI - Incorporating genetic counseling into clinical care for children and adolescents with cancer. PMID- 26888169 TI - Assessing quality-of-life outcomes in cardiovascular clinical research. AB - The field of quality-of-life (QOL) measurement grew out of attempts in the 1960s and 1970s to connect the ever-increasing levels of public expenditure on technology-based health care for chronic diseases with evidence of the benefits and harms to patients. Most of the concepts, methods, and standards for measuring QOL were derived from psychometrics, but the degree to which current tools adhere to these methods varies greatly. Despite the importance of QOL, patient-reported outcomes are not measured in most cardiovascular clinical trials. Lack of familiarity with QOL measures and their interpretation, and unrealistic expectations about the information these measures can provide, are obstacles to their use. Large clinical trials of revascularization therapy for coronary artery disease and medical treatments for heart failure show small-to-moderate QOL effects, primarily detected with disease-specific instruments. Larger treatment effects, seen in trials of device therapy for heart failure and ablation therapy for atrial fibrillation, have been detected with both generic and disease specific instruments. A large gap remains between the parameters currently being measured in clinical research and the data needed to incorporate the 'patient's voice' into therapeutic decision-making. PMID- 26888177 TI - The Spark of Life: Engaging the Cortico-Truncoreticulo-Propriospinal Pathway by Electrical Stimulation. PMID- 26888176 TI - Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. AB - Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID- 26888178 TI - Classification and rates of adverse events in a Malawi male circumcision program: impact of quality improvement training. AB - BACKGROUND: Assessing safety outcomes is critical to inform optimal scale-up of voluntary medical male circumcision (VMMC) programs. Clinical trials demonstrated adverse event (AE) rates from 1.5 to 8 %, but we have limited data on AEs from VMMC programs. METHODS: A group problem-solving, quality improvement (QI) project involving retrospective chart audits, case-conference AE classification, and provider training was conducted at a VMMC clinic in Malawi. For each identified potential AE, the timing, assessment, treatment, and resolution was recorded, then a clinical team classified each event for type and severity. During group discussions, VMMC providers were queried regarding lessons learned and challenges in providing care. After baseline evaluation, clinicians and managers initiated a QI plan to improve AE assessment and management. A repeat audit 6 months later used similar methods to assess the proportions and severity of AEs after the QI intervention. RESULTS: Baseline audits of 3000 charts identified 418 possible AEs (13.9 %), including 152 (5.1 %) excluded after determination of provider misclassification. Of the 266 remaining AEs, the team concluded that 257 were procedure-related (8.6 AEs per 100 VMMC procedures), including 6 (0.2 %) classified as mild, 218 (7.3 %) moderate, and 33 (1.1 %) severe. Structural factors found to contribute to AE rates and misclassification included: provider management of post-operative inflammation was consistent with national guidelines for urethral discharge; available antibiotics were from the STI formulary; providers felt well-trained in surgical skills but insecure in post-operative assessment and care. After implementation of the QI plan, a repeat process evaluating 2540 cases identified 115 procedure-related AEs (4.5 AEs per 100 VMMC procedures), including 67 (2.6 %) classified as mild, 28 (1.1 %) moderate, and 20 (0.8 %) severe. Reports of AEs decreased by 48 % (from 8.6 to 4.5 per 100 VMMC procedures, p < 0.001). Reports of moderate-plus-severe (program-reportable) AEs decreased by 75 % (from 8.4 to 1.9 per 100 VMMC procedures, p < 0.001). CONCLUSIONS: AE rates from our VMMC program implementation site were within the range of clinical trial experiences. A group problem-solving QI intervention improved post-operative assessment, clinical management, and AE reporting. Our QI process significantly improved clinical outcomes and led to more accurate reporting of overall and program-reportable AEs. PMID- 26888180 TI - Aging effects in sequential modulations of poorer-strategy effects during execution of memory strategies. AB - In this study, we asked young adults and older adults to encode pairs of words. For each item, they were told which strategy to use, interactive imagery or rote repetition. Data revealed poorer-strategy effects in both young adults and older adults: Participants obtained better performance when executing better strategies (i.e., interactive-imagery strategy to encode pairs of concrete words; rote repetition strategy on pairs of abstract words) than with poorer strategies (i.e., interactive-imagery strategy on pairs of abstract words; rote-repetition strategy on pairs of concrete words). Crucially, we showed that sequential modulations of poorer-strategy effects (i.e., poorer-strategy effects being larger when previous items were encoded with better relative to poorer strategies), previously demonstrated in arithmetic, generalise to memory strategies. We also found reduced sequential modulations of poorer-strategy effects in older adults relative to young adults. Finally, sequential modulations of poorer-strategy effects correlated with measures of cognitive control processes, suggesting that these processes underlie efficient trial-to-trial modulations during strategy execution. Differences in correlations with cognitive control processes were also found between older adults and young adults. These findings have important implications regarding mechanisms underlying memory strategy execution and age differences in memory performance. PMID- 26888179 TI - Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes. AB - Inherited cardiac conditions (ICCs) are characterised by marked genetic and allelic heterogeneity and require extensive sequencing for genetic characterisation. We iteratively optimised a targeted gene capture panel for ICCs that includes disease-causing, putatively pathogenic, research and phenocopy genes (n = 174 genes). We achieved high coverage of the target region on both MiSeq (>99.8% at >= 20* read depth, n = 12) and NextSeq (>99.9% at >= 20*, n = 48) platforms with 100% sensitivity and precision for single nucleotide variants and indels across the protein-coding target on the MiSeq. In the final assay, 40 out of 43 established ICC genes informative in clinical practice achieved complete coverage (100 % at >= 20*). By comparison, whole exome sequencing (WES; ~ 80*), deep WES (~ 500*) and whole genome sequencing (WGS; ~ 70*) had poorer performance (88.1, 99.2 and 99.3% respectively at >= 20*) across the ICC target. The assay described here delivers highly accurate and affordable sequencing of ICC genes, complemented by accessible cloud-based computation and informatics. See Editorial in this issue (DOI: 10.1007/s12265-015-9667-8 ). PMID- 26888182 TI - Generation of elliptically polarized nitrogen ion laser fields using two-color femtosecond laser pulses. AB - We experimentally investigate generation of nitrogen molecular ion (N2+) lasers with two femtosecond laser pulses at different wavelengths. The first pulse serves as the pump which ionizes the nitrogen molecules and excites the molecular ions to excited electronic states. The second pulse serves as the probe which leads to stimulated emission from the excited molecular ions. We observe that changing the angle between the polarization directions of the two pulses gives rise to elliptically polarized N2+ laser fields, which is interpreted as a result of strong birefringence of the gain medium near the wavelengths of the N2+ laser. PMID- 26888181 TI - Circulating fibroblast growth factor-23 plasma levels predict adverse cardiovascular outcomes in patients with diabetes mellitus with coronary artery disease. AB - BACKGROUND: Abnormalities of fibroblast growth factor-23 (FGF-23) plasma levels predict adverse outcomes in patients with coronary artery disease. However, FGF 23 has a different behaviour in the presence of type 2 diabetes mellitus (T2D). We explored whether the presence of T2D affects the predictive power of FGF-23. METHODS: In 704 patients with stable coronary artery disease, FGF-23, calcidiol, parathormone (PTH) and phosphate plasma levels were prospectively assessed. The primary outcome was the development of acute ischemic events (acute coronary syndrome, stroke or transient ischemic attack), heart failure or death. RESULTS: One hundred seventy-three (24.6%) patients had T2D, without differences in age, sex or estimated glomerular filtration rate as compared with non-diabetic patients. Serum PTH was lower and phosphate higher in T2D than in non-diabetic patients, without differences in FGF-23 or calcidiol levels. During follow-up (2.15 +/- 0.99 years), 26 (15.2%) T2D and 51 (9.6%) non-diabetic patients developed the outcome (p = 0.048). T2D patients who developed the outcome had higher FGF-23 [112.0 (59.9, 167.6) vs 68.9 (54.2, 93.0) RU/mL; p = 0.002], PTH [71.3 (47.3, 106.6) vs 51.9 (40.8, 66.2) pg/mL; p = 0.004) and phosphate (3.53 +/ 0.71 vs 3.25 +/- 0.50 mg/dL; p = 0.017) levels than T2D subjects who remained stable. These differences were not significant in non-diabetic patients. By multivariable Cox proportional hazard model, FGF-23 predicted independently the outcome in T2D patients [hazard ratio = 1.277; 95% CI (1.132, 1.442)] but not in those without T2D. CONCLUSIONS: FGF-23 plasma levels predict adverse cardiovascular outcomes in coronary artery disease patients who have T2D but not in those without T2D. This finding should be confirmed in larger studies. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888183 TI - Monoclonal antibody therapy in multiple myeloma: where do we stand and where are we going? AB - Multiple myeloma is a plasma cell malignancy that is characterized by refractory and relapsing course of disease. Despite the introduction of high-dose chemotherapy in combination with autologous stem cell transplantation and innovative agents such as proteasome inhibitors and immunomodulatory drugs, achieving cure in multiple myeloma is a challenging endeavor. In the last couple of years, enormous advances were made in implementing monoclonal antibody therapy in multiple myeloma. A large number of preclinical and clinical studies have been introduced successfully, demonstrating a safe and efficient administration of monoclonal antibodies in multiple myeloma. In particular, the application of monoclonal antibodies in combination with immunomodulatory drugs, proteasome inhibitors, corticosteroids or conventional chemotherapy seem to be promising and will expand the treatment arsenal for patients with multiple myeloma. PMID- 26888184 TI - The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. AB - AIMS: Thromboembolic risk stratification schemes and clinical guidelines for atrial fibrillation (AF) regard risk as independent of classification into paroxysmal (PAF) and non-paroxysmal atrial fibrillation (NPAF). The aim of the current study was to conduct a systematic review evaluating the impact of AF type on thromboembolism, bleeding, and mortality. METHODS AND RESULTS: PubMed was searched through 27 November 2014 for randomized controlled trials, cohort studies, and case series reporting prospectively collected clinical outcomes stratified by AF type. The incidence of thromboembolism, mortality, and bleeding was extracted. Atrial fibrillation clinical outcome data were extracted from 12 studies containing 99 996 patients. The unadjusted risk ratio (RR) for thromboembolism in NPAF vs. PAF was 1.355 (95% CI: 1.169-1.571, P < 0.001). In the study subset off oral anticoagulation, unadjusted RR was 1.689 (95% CI: 1.151 2.480, P = 0.007). The overall multivariable adjusted hazard ratio (HR) for thromboembolism was 1.384 (95% CI: 1.191-1.608, P < 0.001). The overall unadjusted RR for all-cause mortality was 1.462 (95% CI: 1.255-1.703, P < 0.001). Multivariable adjusted HR for all-cause mortality was 1.217 (95% CI: 1.085-1.365, P < 0.001). Rates of bleeding were similar, with unadjusted RR 1.00 (95% CI: 0.919-1.087, P = 0.994) and adjusted HR 1.025 (95% CI: 0.898-1.170, P = 0.715). CONCLUSION: Non-paroxysmal atrial fibrillation is associated with a highly significant increase in thromboembolism and death. These data suggest the need for new therapies to prevent AF progression and further studies to explore the integration of AF type into models of thromboembolic risk. PMID- 26888185 TI - Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System. AB - Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-gamma) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 MUg Co.120, 16.7 MUg E1.340, 16.7 MUg E2.680, and 10 MUg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN gamma secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV. PMID- 26888186 TI - Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV. AB - Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV. PMID- 26888189 TI - The O-antigen Mediates Differential Survival of Salmonella Against Communities of Natural Predators. AB - Antigenically-distinct members of bacterial species can be differentially distributed in the environment. Predators known to consume antigenically-distinct prey with different efficiencies are also differentially distributed. Here we show that antigenically-distinct, but otherwise isogenic and physiologically indistinct, strains of Salmonella enterica show differential survival in natural soil, sediment and intestinal environments where they would face a community of predators. Decline in overall cell numbers is attenuated by factors that inhibit the action of predators, including heat and antiprotozoal and antihelminthic drugs. Moreover, the fitnesses of strains facing these predators - calculated by comparing survival with and without treatments attenuating predator activity - vary between environments. These results suggest that relative survival in natural environments is arbitrated by communities of natural predators whose feeding preferences, if not species composition, varies between environments. These data support the hypothesis that survival against natural predators may drive the differential distribution of bacteria among microenvironments. PMID- 26888188 TI - Multimetallic Architectures from the Self-assembly of Amino Acids and Tris(2 pyridylmethyl)amine Zinc(II) Complexes: Circular Dichroism Enhancement by Chromophores Organization. AB - Stereodynamic optical probes are becoming very popular for their capability to act as molecular sensors for the determination of the enantiomeric excess (ee) of chiral compounds. Herein, we describe a new molecular architecture formed by the self-assembly of three zinc metal ions, two modified tris(2-pyridylmethyl)amine ligands, and two amino acids. This system is the structural and functional serendipitous evolution of our previous probe for the determination of amino acids ee. In the new system, one of the metals templates in close proximity two chromophores enhancing their exciton coupling. PMID- 26888192 TI - IgE to novel citrus seed allergens among cashew-allergic children. PMID- 26888190 TI - Chronic Meningitis: Simplifying a Diagnostic Challenge. AB - Chronic meningitis can be a diagnostic dilemma for even the most experienced clinician. Many times, the differential diagnosis is broad and encompasses autoimmune, neoplastic, and infectious etiologies. This review will focus on a general approach to chronic meningitis to simplify the diagnostic challenges many clinicians face. The article will also review the most common etiologies of chronic meningitis in some detail including clinical presentation, diagnostic testing, treatment, and outcomes. By using a case-based approach, we will focus on the key elements of clinical presentation and laboratory analysis that will yield the most rapid and accurate diagnosis in these complicated cases. PMID- 26888187 TI - TNFalpha induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion. AB - Transient receptor potential (TRP) A1 and V1 channels relay sensory signals, yet little is known about their transport to the plasmalemma during inflammation. Herein, TRPA1 and TRPV1 were found on vesicles containing calcitonin gene-related peptide (CGRP), accumulated at sites of exo- and endo-cytosis, and co-localised on fibres and cell bodies of cultured sensory neurons expressing both. A proinflammatory cytokine, TNFalpha, elevated their surface content, and both resided in close proximity, indicating co-trafficking. Syntaxin 1-interacting protein, Munc18-1, proved necessary for the response to TNFalpha, and for TRPV1 triggered CGRP release. TNFalpha-induced surface trafficking of TRPV1 and TRPA1 required a synaptic vesicle membrane protein VAMP1 (but not 2/3), which is essential for CGRP exocytosis from large dense-core vesicles. Inactivation of two proteins on the presynaptic plasma membrane, syntaxin-1 or SNAP-25, by botulinum neurotoxin (BoNT)/C1 or /A inhibited the TNFalpha-elevated delivery. Accordingly, enhancement by TNFalpha of Ca(2+) influx through the upregulated surface expressed TRPV1 and TRPA1 channels was abolished by BoNT/A. Thus, in addition, the neurotoxins' known inhibition of the release of pain transmitters, their therapeutic potential is augmented by lowering the exocytotic delivery of transducing channels and the resultant hyper-sensitisation in inflammation. PMID- 26888194 TI - Effective communication in eliciting and responding to suicidal thoughts: a systematic review protocol. AB - BACKGROUND: In the UK, over 6500 people die by suicide each year. In England alone, this is one person every 2 h. Professionals assess risk of suicide in face to-face contacts with people potentially at risk. The National Confidential Inquiry into Suicide found that most people who took their life were classified as 'low risk' in their final contact with mental health services. Training for front-line staff in reducing suicide is a NHS priority. While there is considerable evidence on what to assess when exploring suicidal ideation, there is little evidence on how to ask sensitive questions to effectively identify suicide risk and how to respond in the treatment encounter to reduce patient distress and suicidal ideation. This is critical for identifying risk and putting appropriate care in place. METHODS: An electronic search will be conducted using MEDLINE, CINAHL, Cochrane Library, EMBASE and PsycINFO databases. Controlled studies of effectiveness will be identified using a predefined search strategy. The focus will be on suicidal thoughts/feelings rather than self-harm without intent to die. Two authors will independently screen articles using predefined inclusion and exclusion criteria and relevant data will be extracted using the Cochrane Collaboration data extraction form for randomised controlled trials (RCTs). Discrepancies between the two authors will be resolved by consensus or by consulting a third author at all levels of screening. We will assess the quality of evidence as well as risk of bias. A meta-analysis will be conducted if participants, interventions and comparisons are sufficiently similar, and we will perform the meta-analysis using Stata data analysis and statistical software. DISCUSSION: The results of this systematic review will be used to guide training and practice for health care professionals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015025867. PMID- 26888195 TI - Getting to know the extracellular vesicle glycome. AB - Extracellular vesicles (EVs) are a diverse population of complex biological particles with diameters ranging from approximately 20 to 1000 nm. Tremendous interest in EVs has been generated following a number of recent, high-profile reports describing their potential utility in diagnostic, prognostic, drug delivery, and therapeutic roles. Subpopulations, such as exosomes, are now known to directly participate in cell-cell communication and direct material transfer. Glycomics, the 'omic' portion of the glycobiology field, has only begun to catalog the surface oligosaccharide and polysaccharide structures and also the carbohydrate-binding proteins found on and inside EVs. The EV glycome undoubtedly contains vital clues essential to better understanding the function, biogenesis, release and transfer of vesicles, however getting at this information is technically challenging and made even more so because of the small physical size of the vesicles and the typically minute yield from physiological-scale biological samples. Vesicle micro-heterogeneity which may be related to specific vesicle origins and functions presents a further challenge. A number of primary studies carried out over the past decade have turned up specific and valuable clues regarding the composition and roles of glycan structures and also glycan binding proteins involved EV biogenesis and transfer. This review explores some of the major EV glycobiological research carried out to date and discusses the potential implications of these findings across the life sciences. PMID- 26888193 TI - Fasciola hepatica in goats from north-western Spain: Risk factor analysis using a capture ELISA. AB - In order to study the seroprevalence of Fasciola hepatica infection in goats from north-western Spain, a total of 603 serum samples from 47 herds were tested using a capture ELISA (MM3-SERO). The identification of risk factors was assessed by a mixed-effects logistic regression analysis. The results showed that F. hepatica is widespread in this area with 57.4% of the herds and 22.7% of the animals testing positive. Breed and age were identified as determining factors for caprine F. hepatica infection. Seroprevalence in cross-bred animals was significantly higher than in the autochthonous Cabra Galega breed. A significantly higher seroprevalence was observed in older animals. The use of locally adapted breeds and the implementation of suitable management practices could provide a substantial improvement over the current F. hepatica control measures carried out in goat herds and should be considered when designing new F. hepatica control programs. PMID- 26888196 TI - Development, Validation, and Implementation of an Innovative Mobile App for Alcohol Dependence Management: Protocol for the SIDEAL Trial. AB - BACKGROUND: Information and communication technologies (ICT) have become one of the main pathways to the new paradigm of increased self-management of chronic conditions such as alcohol dependence. Validation of some mobile phone apps has begun, while validation of many others is forthcoming. OBJECTIVE: To describe the protocol for validation of a new app called SIDEAL (an acronym of the Spanish name "Soporte Innovador a la persona con DEpendencia del ALcohol," or innovative support for people with alcohol dependence). METHODS: The project consists of 3 complementary, consecutive studies, including a pilot feasibility study, a qualitative study using focus groups, and, finally, a randomized controlled trial where patients will be randomized to standard treatment or standard treatment plus SIDEAL. During the pilot study, feasibility, usability, and acceptance by users will be the main outcomes explored. An electronic questionnaire will be sent to patients asking for their opinions. Focus groups will be the next step, after which improvements and refinements will be implemented in the app. During the final phase, consumption variables (heavy drinking days per month, mean standard drinks per day) will be investigated, in order to test app efficacy. RESULTS: Because of the encouraging results with previous similar apps, we expect patients to widely accept and incorporate SIDEAL into their therapeutic options. Significant reductions in drinking-related variables are also expected. The pilot study has concluded with the inclusion of 29 patients. Results are expected to be available soon (expected mid-2016). CONCLUSIONS: SIDEAL may represent a useful, reliable, effective, and efficient tool to complement therapeutic options available to both patients and professionals. PMID- 26888198 TI - Kentucky's Medicaid Expansion Showing Early Promise On Coverage And Access To Care. AB - Kentucky is one of only two southern states, at the time of this writing, to have expanded Medicaid under the Affordable Care Act. The expansion raised Medicaid eligibility levels as a means to make coverage more accessible and make health care more affordable for a population likely to face financial barriers in using medical care. This article examines the first-year impact of Kentucky's Medicaid expansion on insurance coverage and access to care. Focusing on Kentucky's low income population, we observed large reductions in the low-income uninsurance rate from 35 percent at the end of 2013 to just below 11 percent by the end of 2014. Other findings revealed declines in unmet medical needs because of cost and declines in the number of people without a readily identifiable source of regular care among low-income groups. While our results are limited to Kentucky's experience with Medicaid expansion, they may hold lessons for other states looking to address health care access issues among their historically vulnerable and low-income populations. PMID- 26888197 TI - Strong hole-doping and robust resistance-decrease in proton-irradiated graphene. AB - Great effort has been devoted in recent years to improve the electrical conductivity of graphene for use in practical applications. Here, we demonstrate the hole carrier density of CVD graphene on a SiO2/Si substrate increases by more than one order of magnitude to n = 3 * 10(13) cm(-2) after irradiation with a high energy 5 MeV proton beam. As a result, the dc-resistance (R) of graphene is reduced significantly by 60%. Only a negligible amount of defect is created by the irradiation. Also the hole-doped low resistance state of graphene remains robust against external perturbations. This carrier doping is achieved without requiring the bias-gate voltage as is the case for other field effect devices. We make two important observations, (i) occurrence of the doping after the irradiation is turned off (ii) indispensability of the SiO2-layer in the substrate, which leads to a purely electronic mechanism for the doping where electron-hole pair creation and interlayer Coulomb attraction play a major role. A flux-dependent study predicts that an ultrahigh doping may be obtained by longer irradiation. We expect the irradiation doping method could be applied to other atomically thin solids, facilitating the fundamental study and application of the 2d materials. PMID- 26888200 TI - Mortality and Rates of Secondary Intervention After EVAR in an Unselected Population: Influence of Simple Clinical Categories and Implications for Surveillance. AB - INTRODUCTION: Post-EVAR surveillance has a major impact upon patients, carers and healthcare resources. We hypothesised that elective indication, on-IFU anatomy, use of a modern device or normal first CTA, or a combination of these categories, might predict a rate of secondary intervention low enough to alter current surveillance protocols. METHODS: Patients undergoing EVAR in our institution between 01.05.2007 and 28.02.2013 were assessed. Data on indication (elective, emergency), anatomy relative to IFU, device, first month CTA result, secondary intervention and mortality were obtained. Kaplan-Meier charts of mortality and freedom from secondary intervention were produced. Statistical analysis was by log-rank test and Cox proportional hazard modelling. RESULTS: 234 patients underwent EVAR (188 elective, 208 on-IFU). Most implants were Endurant (106) or Talent (98). 151 patients had a normal first CTA. By median follow-up of 38.6 months, 39 patients underwent secondary intervention. A normal first CTA and elective indication were significantly associated with reduced risk of secondary intervention (p < 0.001 and p = 0.042 respectively), but device type and placement on- or off-IFU were not. Elective placement with a normal first CTA was 93 % predictive of freedom from secondary intervention by 32 months post-EVAR. Of nine patients undergoing secondary intervention in this group, eight presented symptomatically. DISCUSSION: In optimal procedural circumstances with normal post procedural imaging, only 7 % of patients undergoing EVAR require secondary intervention, a minority of which is driven by surveillance. These data support a change to surveillance more tailored to the individual patient, and highlight the need for further qualitative and quantitative research. PMID- 26888199 TI - Depression motivates quit attempts but predicts relapse: differential findings for gender from the International Tobacco Control Study. AB - AIMS: To determine whether signs of current depression predict attempts to quit smoking, and short-term abstinence among those who try, and to test moderating effects of gender and cessation support (pharmacological and behavioural). DESIGN: Prospective cohort with approximately annual waves. Among smokers at one wave we assessed outcomes at the next wave using mixed-effects logistic regressions. SETTING: Waves 5-8 of the Four Country International Tobacco Control Study: a quasi-experimental cohort study of smokers from Canada, USA, UK and Australia. PARTICIPANTS: A total of 6811 tobacco smokers who participated in telephone surveys. MEASUREMENTS: Three-level depression index: (1) neither low positive affect (LPA) nor negative affect (NA) in the last 4 weeks; (2) LPA and/or NA but not diagnosed with depression in the last 12 months; and (3) diagnosed with depression. Outcomes were quit attempts and 1-month abstinence among attempters. FINDINGS: Depression positively predicted quit attempts, but not after controlling for quitting history and motivational variables. Controlling for all covariates, depression consistently negatively predicted abstinence. Cessation support did not moderate this effect. There was a significant interaction with gender for quit attempts (P = 0.018) and abstinence (P = 0.049) after controlling for demographics, but not after all covariates. Depression did not predict abstinence among men. Among women, depressive symptoms [odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.49-0.81] and diagnosis (OR = 0.46, 95% CI = 0.34-0.63) negatively predicted abstinence. CONCLUSIONS: Smokers with depressive symptoms or diagnosis make more quit attempts than their non-depressed counterparts, which may be explained by higher motivation to quit, but they are also more likely to relapse in the first month. These findings are stronger in women than men. PMID- 26888201 TI - Alternative methods for the Plasmodium falciparum artemisinin ring-stage survival assay with increased simplicity and parasite stage-specificity. AB - BACKGROUND: Artemisinin-based combination therapy is recommended to treat Plasmodium falciparum worldwide, but observations of longer artemisinin (ART) parasite clearance times (PCTs) in Southeast Asia are widely interpreted as a sign of potential ART resistance. In search of an in vitro correlate of in vivo PCT after ART treatment, a ring-stage survival assay (RSA) of 0-3 h parasites was developed and linked to polymorphisms in the Kelch propeller protein (K13). However, RSA remains a laborious process, involving heparin, Percoll gradient, and sorbitol treatments to obtain rings in the 0-3 h window. Here two alternative RSA protocols are presented and compared to the standard Percoll-based method, one highly stage-specific and one streamlined for laboratory application. METHODS: For all protocols, P. falciparum cultures were synchronized with 5 % sorbitol treatment twice over two intra-erythrocytic cycles. For a filtration based RSA, late-stage schizonts were passed through a 1.2 MUm filter to isolate merozoites, which were incubated with uninfected erythrocytes for 45 min. The erythrocytes were then washed to remove lysis products and further incubated until 3 h post-filtration. Parasites were pulsed with either 0.1 % dimethyl sulfoxide (DMSO) or 700 nM dihydroartemisinin in 0.1 % DMSO for 6 h, washed twice in drug-free media, and incubated for 66-90 h, when survival was assessed by microscopy. For a sorbitol-only RSA, synchronized young (0-3 h) rings were treated with 5 % sorbitol once more prior to the assay and adjusted to 1 % parasitaemia. The drug pulse, incubation, and survival assessment were as described above. RESULTS: Ring-stage survival of P. falciparum parasites containing either the K13 C580 or C580Y polymorphism (associated with low and high RSA survival, respectively) were assessed by the described filtration and sorbitol-only methods and produced comparable results to the reported Percoll gradient RSA. Advantages of both new methods include: fewer reagents, decreased time investment, and fewer procedural steps, with enhanced stage-specificity conferred by the filtration method. CONCLUSIONS: Assessing P. falciparum ART sensitivity in vitro via RSA can be streamlined and accurately evaluated in the laboratory by filtration or sorbitol synchronization methods, thus increasing the accessibility of the assay to research groups. PMID- 26888204 TI - The Rainbow Becomes a Spectrum. PMID- 26888202 TI - Fungal-mediated consolidated bioprocessing: the potential of Fusarium oxysporum for the lignocellulosic ethanol industry. AB - Microbial bioprocessing of lignocellulose to bioethanol still poses challenges in terms of substrate catabolism. The most important challenge is to overcome substrate recalcitrance and to thus reduce the number of steps needed to biorefine lignocellulose. Conventionally, conversion involves chemical pretreatment of lignocellulose, followed by hydrolysis of biomass to monomer sugars that are subsequently fermented into bioethanol. Consolidated bioprocessing (CBP) has been suggested as an efficient and economical method of manufacturing bioethanol from lignocellulose. CBP integrates the hydrolysis and fermentation steps into a single process, thereby significantly reducing the amount of steps in the biorefining process. Filamentous fungi are remarkable organisms that are naturally specialised in deconstructing plant biomass and thus they have tremendous potential as components of CBP. The fungus Fusarium oxysporum has potential for CBP of lignocellulose to bioethanol. Here we discuss the complexity and potential of CBP, the bottlenecks in the process, and the potential influence of fungal genetic diversity, substrate complexity and new technologies on the efficacy of CPB of lignocellulose, with a focus on F. oxysporum. PMID- 26888203 TI - Diverse effects of a biosurfactant from Rhodococcus ruber IEGM 231 on the adhesion of resting and growing bacteria to polystyrene. AB - This study evaluated the effects of a trehalolipid biosurfactant produced by Rhodococcus ruber IEGM 231 on the bacterial adhesion and biofilm formation on the surface of polystyrene microplates. The adhesion of Gram-positive (Arthrobacter simplex, Bacillus subtilis, Brevibacterium linens, Corynebacterium glutamicum, Micrococcus luteus) and Gram-negative (Escherichia coli, Pseudomonas fluorescencens) bacteria correlated differently with the cell hydrophobicity and surface charge. In particular, exponentially growing bacterial cells with increased hydrophobicities adhered stronger to polystyrene compared to more hydrophilic stationary phase cells. Also, a moderate correlation (0.56) was found between zeta potential and adhesion values of actively growing bacteria, suggesting that less negatively charged cells adhered stronger to polystyrene. Efficient biosurfactant concentrations (10-100 mg/L) were determined, which selectively inhibited (up to 76 %) the adhesion of tested bacterial cultures, however without inhibiting their growth. The biosurfactant was more active against growing bacteria rather than resting cells, thus showing high biofilm preventing properties. Contact angle measurements revealed more hydrophilic surface of the biosurfactant-covered polystyrene compared to bare polystyrene, which allowed less adhesion of hydrophobic bacteria. Furthermore, surface free energy calculations showed a decrease in the Wan der Waals (gamma(LW)) component and an increase in the acid-based (gamma(AB)) component caused by the biosurfactant coating of polysterene. However, our results suggested that the biosurfactant inhibited the adhesion of bacteria independently on their surface charges. AFM scanning revealed three-type biosurfactant structures (micelles, cord-like assemblies and large vesicles) formed on glass, depending on concentrations used, that could lead to diverse anti-adhesive effects against different bacterial species. PMID- 26888205 TI - The health performance of imported Boer goat (Capra hircus) and their crosses with Woito-guji goat breeds in South Omo Zone, South-Western Ethiopia. AB - Goat production in Ethiopia is constrained by various bottlenecks and low genetic performance of local breeds is among them. Southern Agricultural Research Institute had introduced Boer goats, for crossing, evaluate and distribute to users. This research was conducted to assess the survivability and productive and reproductive performance of Boers and its crosses, on animals managed in on station, Jinka Research Center and Key-afer Goat Research Station from January 2011 to March 2014. The diseases affecting the imported flock were heart water, pyogenic infections/caseous lymphadenitis, and wart/orf diseases with crude mortality rate of 47.6% and case fatality rates of 40.7, 2.4, and 4.7%, respectively. Heart water was responsible for 85% of the overall deaths. The twining percentage of Boer goats was found to be 36.3%, which was by far superior to that of Woito-guji breeds. The mortality rate in 50% crosses was found to be 35.2%; 54.5 and 20.6% in Jinka and Key-afer, respectively. The survival rate of 50% cross kids was found to be associated with birth weight and location. The average birth weight and 1 month weight of 75% crosses was found to be 3.25 +/- 0.43 and 7.12 +/- 1.57 kg, respectively. The 75% crosses survival rate up to weaning was found to be 100%. Despite improvement in productive and reproductive performance through increased exotic blood level, the survivability was strangely questioned for pure and higher blood levels in South Omo Zone. Pure Boer and 75% crosses could better adapt and perform in intensive and semi-intensive production systems. Small holder and pastoral livestock production systems, like South Omo Zone area, should focus on managing 50 % cross sires and rearing 25% crosses for market. PMID- 26888207 TI - Change in growth performance of crossbred (Ankole * Jersey) dairy heifers fed on forage grass diets supplemented with commercial concentrates. AB - Rearing heifers for dairy cow replacement is a challenge in smallholder dairy farms in the tropics due to feed shortage. The objective of this study was to evaluate Brachiaria hybrid cultivar Mulato II as a forage resource for improving growth performance of dairy heifers under cut-and-carry feeding system in Rwanda. Sixteen crossbred (Ankole * Jersey) heifers (mean weight 203 +/- 35 kg) were randomly allocated to two dietary treatments viz: Mulato II with 2 kg/day of commercial concentrates (MCC) and Napier grass (Pennisetum purpureum) with the same supplement (NCC), for a period of 12 weeks. Mineral lick and water were provided ad libitum. Daily feed intake and fortnightly live weight were measured. Average daily gains and feed conversion ratio (FCR) were calculated. Results showed that absolute daily dry matter intake (g DMI/day) and relative intake (g/kg of metabolic body weight--BW(0.75)) were higher in heifers fed on MCC than in heifers fed on NCC (P < 0.001). FCR was lower (P < 0.001) in MCC than NCC diets. Final body weight (FBW) and body weight gain (BWG) did not differ between the two groups of heifers (P > 0.05). Average daily weight gain (ADWG) also not differed significantly (P > 0.05). Based on numerical body weight changes and nutritive values, Mulato II showed potential to be integrated into local cut-and carry feeding systems for better heifer rearing to facilitate dairy cow replacement. PMID- 26888206 TI - Infections and risk factors for livestock with species of Anaplasma, Babesia and Brucella under semi-nomadic rearing in Karamoja Region, Uganda. AB - A survey was conducted to estimate the prevalence of Anaplasma, Babesia and Brucella spp. infections in cattle, goats and sheep in the Karamoja Region of Uganda and to identify possible risk factors existing in this semi-nomadic and pastoral area. Low cost laboratory tests were used to diagnose infections (Rose Bengal test for Brucella spp. antibodies and direct microscopic examination for Anaplasma and Babesia spp.). Multivariable logistic regression models were applied to identify possible risk factors linked to gender, animal species, age (only for cattle) and districts. A total of 3935 cattle, 729 goats and 306 sheep of five districts of the Karamoja Region were tested. Seroprevalence for Brucella was 9.2 % (CI, 95 %: 8.4-10), for Anaplasma 19.5 % (CI 95 %: 18.4-20.6) and for Babesia 16 % (CI 95 %: 15-17.1). Significant differences in infections prevalence were observed against risk factors associated with districts and species. Cattle were the species with higher risk of the infections. Female gender was identified as at risk only for Brucella spp. infection. Cattle more than one year old had greater likelihood to be Brucella seropositive. Co-infections of Anaplasma and Babesia spp. were statistically associated, especially in goats and sheep. Further studies to identify risk factors related to host species and geographical districts are needed. The influence on the semi-nomadic agro-pastoral system in Karamoja of animal raids and animal mixing should be further investigated. Findings were important to sensitize Karamojong undertaking measures on infection control, especially on cattle, which are their main source of food. PMID- 26888208 TI - The effects of low-intensity narrow-band blue-light treatment compared to bright white-light treatment in sub-syndromal seasonal affective disorder. AB - BACKGROUND: The discovery of a novel photoreceptor in the retinal ganglion cells with a highest sensitivity of 470-490 nm blue light has led to research on the effects of short-wavelength light in humans. Several studies have explored the efficacy of monochromatic blue or blue-enriched light in the treatment of SAD. In this study, a comparison has been made between the effects of broad-wavelength light without ultraviolet (UV) wavelengths compared to narrow-band blue light in the treatment of sub-syndromal seasonal affective disorder (Sub-SAD). METHOD: In a 15-day design, 48 participants suffering from Sub-SAD completed 20-minute sessions of light treatment on five consecutive days. 22 participants were given bright white-light treatment (BLT, broad-wavelength light without UV 10 000 lux, irradiance 31.7 Watt/m(2)) and 26 participants received narrow-band blue light (BLUE, 100 lux, irradiance 1.0 Watt/m(2)). All participants completed daily and weekly questionnaires concerning mood, activation, sleep quality, sleepiness and energy. Also, mood and energy levels were assessed by means of the SIGH-SAD, the primary outcome measure. RESULTS: On day 15, SIGH-SAD ratings were significantly lower than on day 1 (BLT 54.8 %, effect size 1.7 and BLUE 50.7 %, effect size 1.9). No statistically significant differences were found on the main outcome measures. CONCLUSION: Light treatment is an effective treatment for Sub-SAD. The use of narrow-band blue-light treatment is equally effective as bright white light treatment. TRIAL REGISTRATION: This study was registered in the Dutch Trial Register (Nederlands Trial Register TC = 4342 ) (20-12-2013). PMID- 26888209 TI - Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers. AB - OBJECTIVE: To determine rates of publication and reporting of results within two years for all completed clinical trials registered in ClinicalTrials.gov across leading academic medical centers in the United States. DESIGN: Cross sectional analysis. SETTING: Academic medical centers in the United States. PARTICIPANTS: Academic medical centers with 40 or more completed interventional trials registered on ClinicalTrials.gov. METHODS: Using the Aggregate Analysis of ClinicalTrials.gov database and manual review, we identified all interventional clinical trials registered on ClinicalTrials.gov with a primary completion date between October 2007 and September 2010 and with a lead investigator affiliated with an academic medical center. MAIN OUTCOME MEASURES: The proportion of trials that disseminated results, defined as publication or reporting of results on ClinicalTrials.gov, overall and within 24 months of study completion. RESULTS: We identified 4347 interventional clinical trials across 51 academic medical centers. Among the trials, 1005 (23%) enrolled more than 100 patients, 1216 (28%) were double blind, and 2169 (50%) were phase II through IV. Overall, academic medical centers disseminated results for 2892 (66%) trials, with 1560 (35.9%) achieving this within 24 months of study completion. The proportion of clinical trials with results disseminated within 24 months of study completion ranged from 16.2% (6/37) to 55.3% (57/103) across academic medical centers. The proportion of clinical trials published within 24 months of study completion ranged from 10.8% (4/37) to 40.3% (31/77) across academic medical centers, whereas results reporting on ClinicalTrials.gov ranged from 1.6% (2/122) to 40.7% (72/177). CONCLUSIONS: Despite the ethical mandate and expressed values and mission of academic institutions, there is poor performance and noticeable variation in the dissemination of clinical trial results across leading academic medical centers. PMID- 26888210 TI - Is the secular trend in height delaying overweight rise among adolescents? The Brazilian case. AB - OBJECTIVE: To explore if the secular trend in height is contributing to delay overweight rise among Brazilian adolescents. DESIGN: Changes in BMI mean over time were fitted using linear regression including as independent variables survey year, height, survey-specific income quintiles, age and an interaction term of height * survey year. Overweight was defined as BMI>=25.0 kg/m2. Changes in overweight prevalence over time were fitted using Poisson regression. SETTING: Four national household surveys: 1974/5, 1989, 2002/3 and 2008/9. SUBJECTS: Brazilian adolescents. RESULTS: Mean values of height and BMI increased over the period, for both sexes and in all age ranges, except for girls aged 14-19 years from 1989 to 2002/3. The highest average increment and mean rate of height were between 1989 and 2002/3 and in 10-15-year-olds. The annual increment of height decreased from 2002/3 to 2008/9 in parallel with the increment in BMI rate. After fitting the regression model, the height * survey year interaction and per capita income were strong vectors to increase BMI mean. Changes in increment rate of height played a protective role against overweight in the last two periods for both sexes, mainly for girls. The period from 1989 to 2002/3 was the strongest vector associated with overweight in boys and the association decreased to the next period, from 2002/3 to 2008/9. CONCLUSIONS: BMI and height of adolescents have increased in a wavering and alternate way throughout four decades in Brazil. The rate of height increment has played a protective role against overweight in adolescents. PMID- 26888211 TI - The architecture of river networks can drive the evolutionary dynamics of aquatic populations. AB - It is widely recognized that physical landscapes can shape genetic variation within and between populations. However, it is not well understood how riverscapes, with their complex architectures, affect patterns of neutral genetic diversity. Using a spatially explicit agent-based modeling (ABM) approach, we evaluate the genetic consequences of dendritic river shapes on local population structure. We disentangle the relative contribution of specific river properties to observed patterns of genetic variation by evaluating how different branching architectures and downstream flow regimes affect the genetic structure of populations situated within river networks. Irrespective of the river length, our results illustrate that the extent of river branching, confluence position, and levels of asymmetric downstream migration dictate patterns of genetic variation in riverine populations. Comparisons between simple and highly branched rivers show a 20-fold increase in the overall genetic diversity and a sevenfold increase in the genetic differentiation between local populations. Given that most rivers have complex architectures, these results highlight the importance of incorporating riverscape information into evolutionary models of aquatic species and could help explain why riverine fishes represent a disproportionately large amount of global vertebrate diversity per unit of habitable area. PMID- 26888212 TI - The anti-inflammation and pharmacokinetics of a novel alkaloid from Portulaca oleracea L. AB - OBJECTIVES: This study was to elucidate the pharmacokinetics of a novel alkaloid, 6-acetyl-2,2,5-trimethyl-2,3-dihydrocyclohepta[b]pyrrol-8(1H)-one, named oleracone isolated from Portulaca oleracea L., and to examine the anti inflammatory ability with lipopolysaccharide (LPS) stimulated macrophages. METHODS: The novel alkaloid, oleracone, was isolated from Portulaca oleracea L., and its structure was determined by spectroscopic analysis including HRESIMS, 2D NMR spectroscopic data and single-crystal X-ray diffraction. The activity of anti inflammation was assayed via the test with RAW 264.7 activated by LPS, and the pharmacokinetics of oleracone in rat plasma after intravenous and oral administration at dose of 2.5 mg/kg was, respectively, investigated by a rapid and sensitive ultra high-performance liquid chromatography (UHPLC) method with bergapten as internal standard. KEY FINDINGS: Oleracone was a novel alkaloid first isolated from Portulaca oleracea L. and possessed unique structure in natural products, whose anti-inflammatory effecting on nitrite oxide production and several pivotal pro-inflammatory cytokines was found at the concentration of 50 MUm, and the pharmacokinetic results indicated that oleracone was rapidly distributed with Tmax of 15.7 min after oral administration and presented a higher oral absolute bioavailability to be 74.91 +/- 10.7%. CONCLUSIONS: Oleracone as novel alkaloid presented remarkably anti-inflammatory effect, which was rapid distributed in rat with high bioavailability of 74.91 +/- 10.7%. PMID- 26888213 TI - Classification of the medicinal plants of the genus Atractylodes using high performance liquid chromatography with diode array and tandem mass spectrometry detection combined with multivariate statistical analysis. AB - Analytical methods using high-performance liquid chromatography with diode array and tandem mass spectrometry detection were developed for the discrimination of the rhizomes of four Atractylodes medicinal plants: A. japonica, A. macrocephala, A. chinensis, and A. lancea. A quantitative study was performed, selecting five bioactive components, including atractylenolide I, II, III, eudesma-4(14),7(11) dien-8-one and atractylodin, on twenty-six Atractylodes samples of various origins. Sample extraction was optimized to sonication with 80% methanol for 40 min at room temperature. High-performance liquid chromatography with diode array detection was established using a C18 column with a water/acetonitrile gradient system at a flow rate of 1.0 mL/min, and the detection wavelength was set at 236 nm. Liquid chromatography with tandem mass spectrometry was applied to certify the reliability of the quantitative results. The developed methods were validated by ensuring specificity, linearity, limit of quantification, accuracy, precision, recovery, robustness, and stability. Results showed that cangzhu contained higher amounts of atractylenolide I and atractylodin than baizhu, and especially atractylodin contents showed the greatest variation between baizhu and cangzhu. Multivariate statistical analysis, such as principal component analysis and hierarchical cluster analysis, were also employed for further classification of the Atractylodes plants. The established method was suitable for quality control of the Atractylodes plants. PMID- 26888214 TI - Inhalation of mercury vapor can cause the toxic effects on rat kidney. AB - Dental amalgam has been used in dentistry as a filling material. The filler comprises mercury (Hg). It is considered one of the most important and widespread environmental pollutants, which poses a serious potential threat for the humans and animals. However, mercury deposition affects the nervous, cardiovascular, pulmonary, gastrointestinal, and especially renal systems. In most animals' species and humans, the kidney is one of the main sites of deposition of mercury and target organ for its toxicity. In this study, the effects of mercury intake on kidney in rats were searched. For the this purpose; we used 24 adult female Wistar albino rats (200 g in weight) obtained from Experimental Research and Application Center of Ataturk University with ethical approval. Besides, they were placed into a specially designed glass cage. Along this experiment for 45 days, subjects were exposed to (1 mg/m(3)/day) mercury vapor. However, no application was used for the control subjects. At the end of the experiment, kidney samples were obtained from all subjects and processed for routine light microscopic level and stereological aspect were assessed. Finally, according to our results, mercury affects the histological features of the kidney. That means, the severe effects of mercury has been shown using stereological approach, which is one of the ideal quantitative methods in the current literature. In this study, it was detected that chronic exposure to mercury vapor may lead to renal damage and diseases in an experimental rat model. PMID- 26888215 TI - Analyses of regulatory CD4+ CD25+ FOXP3+ T cells and observations from peripheral T cell subpopulation markers during the development of type 1 diabetes in children. AB - Our aim was to study whether the aberrant amount or function of regulatory T cells is related to the development of type 1 diabetes (T1D) in children. We also set out to investigate the balance of different T cell subtype markers during the T1D autoimmune process. Treg cells were quantified with flow cytometric assay, and the suppression capacity was analysed with a carboxyfluorescein succinimidyl ester (CFSE)-based T cell suppression assay in children in various phases of T1D disease process and in healthy autoantibody-negative control children. The mRNA expression of different T cell subpopulation markers was analysed with real-time qPCR method. The proportion and suppression capacity of regulatory T cells were similar in seroconverted children at an early stage of beta cell autoimmunity and also in children with T1D when compared to healthy and autoantibody-negative children. Significant differences were observed in the mRNA expression of different T cell subpopulation markers in prediabetic children with multiple (>= 2) autoantibodies and in children with newly diagnosed T1D when compared to the control children. In conclusion, there were no quantitative or functional differences in regulatory T cells between the case and control groups in any phase of the autoimmune process. Decreased mRNA expression levels of T cell subtype markers were observed in children with multiple islet autoantibodies and in those with newly diagnosed T1D, probably reflecting an exhaustion of the immune system after the strong immune activation during the autoimmune process or a generally aberrant immune response related to the progression of the disease. PMID- 26888216 TI - SMARCAD1 is an ATP-dependent stimulator of nucleosomal H2A acetylation via CBP, resulting in transcriptional regulation. AB - Histone acetylation plays a pivotal role in transcriptional regulation, and ATP dependent nucleosome remodeling activity is required for optimal transcription from chromatin. While these two activities have been well characterized, how they are coordinated remains to be determined. We discovered ATP-dependent histone H2A acetylation activity in Drosophila nuclear extracts. This activity was column purified and demonstrated to be composed of the enzymatic activities of CREB binding protein (CBP) and SMARCAD1, which belongs to the Etl1 subfamily of the Snf2 family of helicase-related proteins. SMARCAD1 enhanced acetylation by CBP of H2A K5 and K8 in nucleosomes in an ATP-dependent fashion. Expression array analysis of S2 cells having ectopically expressed SMARCAD1 revealed up-regulated genes. Using native genome templates of these up-regulated genes, we found that SMARCAD1 activates their transcription in vitro. Knockdown analysis of SMARCAD1 and CBP indicated overlapping gene control, and ChIP-seq analysis of these commonly controlled genes showed that CBP is recruited to the promoter prior to SMARCAD1. Moreover, Drosophila genetic experiments demonstrated interaction between SMARCAD1/Etl1 and CBP/nej during development. The interplay between the remodeling activity of SMARCAD1 and histone acetylation by CBP sheds light on the function of chromatin and the genome-integrity network. PMID- 26888217 TI - Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial. AB - BACKGROUND: Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. METHOD/DESIGN: ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. DISCUSSION: As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012. PMID- 26888218 TI - Multivariable analysis of total cholesterol levels in male Swiss Armed Forces conscripts 2006-2012 (N = 174,872). AB - BACKGROUND: Cholesterol is an important contributor to morbidity and mortality risks due to its association with obesity, cardiovascular disease, and cancer. A system of mandatory military conscription is a useful tool for disease-risk monitoring in a given male population. Swiss military conscription data are representative for more than 90% of a given male birth cohort (with Swiss citizenship). The medical examination also includes voluntary laboratory testing, for which approximately 65% of the young men present at conscription give consent. METHODS: Here we present the temporal and subgroup analyses of total serum cholesterol levels (TCL) among Swiss conscripts from 2006 to 2012 (N = 174,872; mean age = 19.75 years). The voluntary blood samples were tested by a central laboratory (Viollier AG) with identical measurement standards and strict quality control. To test differences in TCL by socioeconomic occupational status, sports test performance, Body Mass Index (BMI), age, and place of residence of the conscripts we used a multivariable regression model with TCL as dependent variable. RESULTS: Mean TCL decreased significantly, by 0.125 mmol/l (95% CI 0.108-0.142, p < 0.001) from 4.225 mmol/l (95% CI 4.210-4.240) in 2006 to 4.100 mmol/l (95% CI 4.091-4.109) in 2012. Similarly, the prevalence of conscripts with an elevated TCL >= 5.17 mmol/l decreased from >= 10.2% prior to 2011 to 6.9% in 2011 and 8.2% in 2012. Multivariate regression showed an association between elevated TCL and lower socioeconomic occupational status, lower sports test performance, higher BMI, higher age, and area of residence. There was no longer a significant increase in mean TCL among the three grades of obesity (BMI >= 30.0 kg/m2) as defined by the WHO. Within the BMI categories of normal weight and overweight, TCL was stratified by sports performance (better sports performance = lower TCL). CONCLUSION: Decreasing TCL in 2011 and 2012 fits the known pattern of conscripted persons' stabilizing BMI and sports test performance of the conscripts in recent years. However, small temporal drifts within the laboratory analyses cannot be ruled out as confounding factors. In conclusion, identifying subgroups with unfavorable lipid profiles will contribute to the continuing success of intensified public health programs. PMID- 26888219 TI - Erratum to: Feasibility, acceptability and potential effectiveness of dignity therapy for family carers of people with motor neurone disease. PMID- 26888220 TI - Oral manifestations of rheumatoid arthritis. A cross-sectional study of 73 patients. AB - OBJECTIVE: A study is made of the main oral manifestations of patients with rheumatoid arthritis (RA), particularly salivary flow, and of its possible association to periodontal disease. MATERIAL AND METHODS: A prospective comparative study was made of 146 patients (73 with RA and 73 controls), recording pocket depth, clinical attachment loss, bleeding index, plaque index, and the DMFT index to assess periodontal and dental alterations. Sialometric measurements were also made to determine resting, stimulated, and parotid salivary flow. RESULTS: The patients with RA had greater periodontal pocket depths (with moderate depths in most cases), as well as greater attachment loss and more bacterial plaque. The resting whole saliva and stimulated parotid saliva rates were also clearly decreased in the RA group compared with the controls. CONCLUSIONS: Patients with RA are more likely to present periodontal disease, poorer oral hygiene manifesting as an increased accumulation of bacterial plaque, and decreased salivary flow rates. CLINICAL RELEVANCE: Vulnerability to periodontitis is confirmed in one of the largest samples ever studied of patients with rheumatoid arthritis (RA). Also, there is evidence of hyposialia (decrease in salivary rate) in RA patients without Sjogren's syndrome. PMID- 26888222 TI - Movement control during aspiration with different injection systems via video monitoring-an in vitro model. AB - OBJECTIVES: The aim of the present study was an evaluation of movement during double aspiration by different manual syringes and one computer-controlled local anesthesia delivery system (C-CLAD). MATERIALS AND METHODS: With five different devices (two disposable syringes (2, 5 ml), two aspirating syringes (active, passive), one C-CLAD), simulation of double aspiration in a phantom model was conducted. Two experienced and two inexperienced test persons carried out double aspiration with the injection systems at the right and left phantom mandibles in three different inclination angles (n = 24 * 5 * 2 for each system). 3D divergences of the needle between aspiration procedures (mm) were measured with two video cameras. RESULTS: An average movement for the 2-ml disposal syringe of 2.85 mm (SD 1.63), for the 5 ml syringe of 2.36 mm (SD 0.86), for the active aspirating syringe of 2.45 mm (SD 0.9), for the passive-aspirating syringe of 2.01 mm (SD 0.7), and for the C-CLAD, an average movement of 0.91 mm (SD 0.63) was seen. The movement was significantly less for the C-CLAD compared to the other systems (p < 0.001). The movement of the needle in the soft tissue was significantly less for the C-CLAD compared to the other systems (p < 0.001). CONCLUSIONS: A difference in involuntary movement of the syringe could be seen in comparison between manual and C-CLAD systems. Launching the aspiration by a foot pedal in computer-assisted anesthesia leads to a minor movement. CLINICAL RELEVANCE: To solve the problem of movement during aspiration with possibly increased false-negative results, a C-CLAD seems to be favorable. PMID- 26888223 TI - Tailoring nonlinear optical properties of Bi2Se3 through ion irradiation. AB - The nonlinear optical property of topological insulator bismuth selenide (Bi2Se3) is found to be well-tailored through ion irradiation by intentionally introducing defects. The increase of the optical modulation depth sensitively depends on the careful selection of the irradiation condition. By implementing the ion irradiated Bi2Se3 film as an optical saturable absorber device for the Q-switched wave-guide laser, an enhanced laser performance has been obtained including narrower pulse duration and higher peak power. Our work provides a new approach of tailoring the nonlinear optical properties of materials through ion irradiation, a well-developed chip-technology, which could find wider applicability to other layered two-dimensional materials beyond topological insulators, such as graphene, MoS2, black phosphours etc. PMID- 26888224 TI - Interface-Induced Renormalization of Electrolyte Energy Levels in Magnesium Batteries. AB - A promising strategy for increasing the energy density of Li-ion batteries is to substitute a multivalent (MV) metal for the commonly used lithiated carbon anode. Magnesium is a prime candidate for such a MV battery due to its high volumetric capacity, abundance, and limited tendency to form dendrites. One challenge that is slowing the implementation of Mg-based batteries, however, is the development of efficient and stable electrolytes. Computational screening for molecular species having sufficiently wide electrochemical windows is a starting point for the identification of optimal electrolytes. Nevertheless, this window can be altered via interfacial interactions with electrodes. These interactions are typically omitted in screening studies, yet they have the potential to generate large shifts to the HOMO and LUMO of the electrolyte components. The present study quantifies the stability of several common electrolyte solvents on model electrodes of relevance for Mg batteries. Many-body perturbation theory calculations based on the G0W0 method were used to predict shifts in a solvent's electronic levels arising from interfacial interactions. In molecules exhibiting large dipole moments, our calculations indicate that these interactions reduce the HOMO-LUMO gap by ~ 25% (compared to isolated molecules). We conclude that electrode interactions can narrow an electrolyte's electrochemical window significantly, thereby accelerating redox decomposition reactions. Accounting for these interactions in screening studies presents an opportunity to refine predictions of electrolyte stability. PMID- 26888221 TI - The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A:IL-17E ratio. AB - OBJECTIVES: The serum IL-17A:IL-17E ratio has previously been demonstrated to be a clinical marker of periodontitis. The aim of this study was to determine the effects of non-surgical periodontal treatment on the serum IL-17A:IL-17E ratio. MATERIALS AND METHODS: Forty chronic periodontitis patients completed this study and received periodontal treatment comprising scaling and root planing plus ultrasonic debridement. Clinical data were recorded at baseline, 6 weeks (R1) after treatment completion (full-mouth or quadrant-scaling and root planing) and 25 weeks after baseline (R2). Serum samples were taken at each time point and cytokines concentrations determined by ELISA. RESULTS: Following treatment, statistically significant reductions were noted in clinical parameters. However, IL-17A and IL-17E concentrations were significantly greater than baseline values before- and after-adjusting for smoking. The IL-17A:IL-17E ratio was lower at R1 and R2. Serum IL-6 and TNF levels were significantly lower at R1 only. Also exclusively at R1, serum IL-17A and IL-17E correlated positively with clinical parameters, while the IL-17A:IL-17E ratio correlated negatively with probing pocket depth and clinical attachment. CONCLUSION: Increased serum IL-17E and a reduced IL-17A:IL-17E ratio may be indicative and/or a consequence of periodontal therapy. Therefore, the role of IL-17E in periodontal disease progression and the healing process is worthy of further investigation. CLINICAL RELEVANCE: IL-17E may be a valuable biomarker to monitor the healing process following periodontal treatment as increased IL-17E levels and a reduced IL-17A:IL-17E ratio could reflect clinical improvements post-therapy. Therefore, monitoring serum IL-17E might be useful to identify individuals who require additional periodontal treatment. PMID- 26888225 TI - Impacts of different climate change regimes and extreme climatic events on an alpine meadow community. AB - Climate variability is expected to increase in future but there exist very few experimental studies that apply different warming regimes on plant communities over several years. We studied an alpine meadow community under three warming regimes over three years. Treatments consisted of (a) a constant level of warming with open-top chambers (ca. 1.9 degrees C above ambient), (b) yearly stepwise increases in warming (increases of ca. 1.0, 1.9 and 3.5 degrees C), and (c) pulse warming, a single first-year pulse event of warming (increase of ca. 3.5 degrees C). Pulse warming and stepwise warming was hypothesised to cause distinct first-year and third-year effects, respectively. We found support for both hypotheses; however, the responses varied among measurement levels (whole community, canopy, bottom layer, and plant functional groups), treatments, and time. Our study revealed complex responses of the alpine plant community to the different experimentally imposed climate warming regimes. Plant cover, height and biomass frequently responded distinctly to the constant level of warming, the stepwise increase in warming and the extreme pulse-warming event. Notably, we found that stepwise warming had an accumulating effect on biomass, the responses to the different warming regimes varied among functional groups, and the short term perturbations had negative effect on species richness and diversity. PMID- 26888226 TI - Geogenic and Anthropogenic Moss Responsiveness to Element Distribution Around a Pb-Zn Mine, Toranica, Republic of Macedonia. AB - Moss species (Homalothecium lutescens, Hypnum cupressiforme, Brachythecium glareosum, and Campthotecium lutescens) were used as suitable sampling media for biomonitoring the origin of heavy-metal pollution in the lead-zinc (Pb-Zn) mine "Toranica" near the Kriva Palanka town, Eastern Macedonia. The contents of 20 elements-silver (Ag), aluminum (Al), arsenic (As), barium (Ba), calcium (Ca), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), potassium (K), lithium (Li), magnesium (Mg), manganese (Mn), sodium (Na), nickel (Ni), Pb, strontium (Sr), vanadium (V), and (Zn) were determined by atomic emission spectrometry with inductively coupled plasma. Data processing was applied with combinations of multivariate statistical methods: factor analysis, principal component analysis, and cluster analysis. Moss' responsiveness to the atmospheric distribution of the selected elements was investigated in correlation to the specific geology of the region (soil dusting). Lithogenic distribution was characterized with the distribution of three dominant geochemical associations: F1: Al-Li-V-Cr-Ni-Co, F2: Ba-Ca-Sr, and F3: Cd-Zn-Pb-Cu. Spatial distribution was constructed for visualization of the factor deposition. Furthermore, air distribution (passive biomonitoring) versus soil geochemistry of the analyzed elements was examined. Significant correlations were singled out for Pb, Zn, and Cd and for Mg(moss)/Na(soil). Characteristic lithological anomaly characterized the presence of the oldest geological volcanic rocks. Zone 1 (Pb-Zn mine surrounding) presents a unique area with hydrothermal action of Pb-Zn mineralization leading to polymetallic enrichments in soil. This phenomenon strongly affects the environment, which is a natural geochemical imprint in this unique area (described with the strong dominance of the geochemical association Cd-Zn-Pb-Cu). PMID- 26888228 TI - Applications of NMR diffusion methods with emphasis on ion pairing in inorganic chemistry: a mini-review. AB - This mini-review provides a brief overview of the use of NMR diffusion methods in connection with estimating molecular weights in solution, recognizing hydrogen bonding and encapsulation processes and, primarily, identifying and estimating the varying degrees of ion pairing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888227 TI - Comparison of the effects of treatment with celecoxib, loxoprofen, and acetaminophen on postoperative acute pain after arthroscopic knee surgery: A randomized, parallel-group trial. AB - BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors, conventional non selective nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen have been adopted for the relief of mild to moderate acute and chronic pain. However, it remains unclarified whether the therapeutic differences in pain sensation exist among these agents. The aim of this study was to compare the efficacy of different types of analgesic agents for postoperative acute pain management. METHODS: A single-center, randomized, controlled study was performed in consecutive patients who underwent the second-look procedure with removal of internal fixation after anterior cruciate ligament reconstruction or arthroscopic meniscal repair/meniscectomy. Celecoxib (400 mg for the first dose and then 200 mg), loxoprofen (60 mg), or acetaminophen (600 mg) was orally administered from postoperative 3 h. The pain intensity on a 100-mm VAS scale and subjective assessment of therapeutic pain-relief were compared among these three treatment groups until postoperative 2 days. The acquired data were analyzed according to the per-protocol analysis principle. RESULTS: A total of 432 patients were screened, and 160 were enrolled. The VAS score tended to decrease over time in all groups. There was a significant improvement in the pain score both at rest and on movement, and subjective impression in the celecoxib-treated group compared with acetaminophen at postoperative 2 days. On the other hand, loxoprofen resulted in the benefit only in the pain score at rest in comparison with acetaminophen. Any comparisons between celecoxib and loxoprofen showed insignificant differences throughout observations. No adverse effects were confirmed in each group. CONCLUSIONS: These obtained findings in our dose setting conditions suggest that celecoxib and loxoprofen treatments were superior to acetaminophen in pain-relief, though the superiority of loxoprofen over acetaminophen was modest. Overall, selective COX-2 inhibitors including conventional NSAIDs seem to have a possible advantage in acute pain management of relatively less invasive surgery. PMID- 26888229 TI - Orchestrating a bold future for IADR. PMID- 26888230 TI - Oral squamous cell carcinoma: Advances in management. PMID- 26888231 TI - The autologous platelet rich fibrin: A novel approach in osseous regeneration after cystic enucleation: A pilot study. AB - CONTEXT: The platelet rich fibrin (PRF) is second generation platelet concentrate that has been widely used and researched for stimulation and acceleration of soft tissue and osseous healing. Its continuous delivery of growth factors and proteins mimic the need of physiological wound healing and regenerative tissue processes. AIMS AND OBJECTIVES: The aim of this study was to evaluate the efficacy of PRF in osseous regeneration after enucleation of cystic lesions. The objectives of this study were: (1) To evaluate osseous regeneration radiographically with the use of PRF in intrabony defects after cystic enucleation. (2) To evaluate the degree of bone density in intrabony defects with the use of PRF postoperatively after 1 st , 3 rd , and 6 th months. SUBJECTS AND METHODS: 10 cases of cystic lesions were treated using PRF after cystic enucleation. Follow-up radiographs (orthopantomogram) were taken 1 st , 3 rd , and 6 th months postoperatively. Bone density was measured with grayscale histogram using Adobe Photoshop 7.0 software. RESULTS: The subsequent follow-up examinations revealed progressive, predictable, and significant radiographic osseous regeneration. CONCLUSION: The use of PRF in management of cystic lesions seems to be a novel therapeutic approach promoting faster osseous regeneration within 6 months postoperatively however further study is required with larger sample size and with a control group. PMID- 26888232 TI - Cell cycle aberration in ameloblastoma and adenomatoid odontogenic tumor: As evidenced by the expression of p53 and survivin. AB - CONTEXT: p53 and survivin are involved in cell cycle progression and inhibition of apoptosis, respectively. Survivin is a unique protein which functions in progression of cell division and inhibits apoptosis leading to cell proliferation and cell survival. According to the literature, mutation of p53 leads to promotion of survivin function. Thus, the importance of cell cycle aberration and uncontrolled proliferation resulting from mutation of p53 and up-regulation of survivin is discussed. AIMS: To assess the role of p53 and survivin in ameloblastoma and adenomatoid odontogenic tumor (AOT). SETTINGS AND DESIGN: The percentages of positive tumor cells were considered for statistical evaluation. Nuclear labeling index for p53 and nuclear, cytoplasmic and combined labeling index for survivin was obtained from the stained slides. MATERIALS AND METHODS: Immunohistochemical expression of p53 and survivin was done qualitatively and quantitatively in 25 cases each of ameloblastoma and AOT. STATISTICAL ANALYSIS USED: Mann-Whitney U-test, Wilcoxon signed ranks test and Pearson's correlation test. RESULTS: Quantitatively, p53 and survivin expression was statistically significant in AOT (P = 0.003) and qualitatively, in ameloblastoma (P = 0.004). Survivin expression was significant (P = 0.002) between the study groups unlike that of p53 (P = 0.554). CONCLUSIONS: There was no much difference in p53 expression in ameloblastoma and AOT suggestive of cell cycle aberration in both the odontogenic tumors, but significant difference in survivin expression in ameloblastoma and AOT with higher percentage of positive cells in ameloblastoma may be indicative of an aggressive behavior of ameloblastoma. PMID- 26888233 TI - Localization of mandibular foramen relative to landmarks in East Indian mandibles. AB - CONTEXT: The position of mandibular foramen (MF) is an important anatomical landmark for effective anesthesia in dentistry for many procedures, including dental extraction from the lower jaw and putting mandibular implants. Several causes have been examined in this context, and the uncertainty in the location of the MF has been examined to be a major factor for the high failure rate of anesthesia and complications of the orthodontic procedure. AIMS: The purpose of this study was to examine and analyze the position of the MF relative to six bony landmarks on the ramus in the population of Jharkhand. SUBJECTS AND METHODS: The different parameters were measured in 30 dry adult's mandibles that were obtained from the Department of Anatomy. The data were tabulated and statistically analyzed. STATISTICAL ANALYSIS USED: Paired t-test. RESULTS: The mean distance between the MF and the respective landmarks was noted as 16.00 +/- 3.50 mm for the anterior border, 10.21 +/- 2.34 mm for the posterior border, 20.48 +/- 3.89 mm for the superior border, 24.15 +/- 4.97 mm for the inferior border, 33.46 +/- 6.08 mm for the condyle, and 12.31 +/- 4.88 mm for the internal oblique ridge for the right side. On the left side, these distances were 16.27 +/- 3.9 for the anterior border, 10.28 +/- 5.24 for the posterior border, 20.15 +/- 3.8 for superior border, 24.86 +/- 4.04 for inferior border 32.48 +/- 4.73 for condyle, and 10.93 +/- 4.06 for the inferior oblique ridge. Statistically, there was no significant difference in the distance to either side from selected 5 landmarks, the only exception being the condyle. CONCLUSIONS: Condyle and internal oblique ridge have been shown to be two new landmarks that may be used to find MF. Bilateral symmetry has been shown for all landmarks except for condyle. PMID- 26888235 TI - Analysis of adverse events with use of orthodontic sequential aligners as reported in the manufacturer and user facility device experience database. AB - BACKGROUND: Sequential aligners (SAs) introduced about a decade ago, changed the practice of orthodontics as we knew it but the adverse events and reactions (AER) associated with SA is not known. The Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database is a reliable database that has AERs reported. The manuscript attempts to review the AER associated with SA using the MAUDE database. MATERIALS AND METHODS: The authors downloaded and reviewed the SA-related AER from MAUDE for a period of 5 years. In-depth analysis of the site and nature of intraoral and extraoral AERs were performed. We attempted to calculate the probability of pathologies being directly related to SA use, using Bayes' theorem. RESULTS: In the study period of 5 years, 175 cases of AER registered with MAUDE database owing to use of SA. Of the 175 cases, 129 (73.71%) instances were mandatory reports filed by the manufacturer. Of all AERs, 32 (18.29%) cases had been diagnosed/suspected to have an allergic reaction, 20 (11.43%) of them with anaphylactic reaction and 4 (2.29%) of them with angioedema. Lesions involving tongue, throat, and lip such as soreness, inflammation, and hives were more commonly reported. In addition, 12 cases (6.86%) reported of nausea, 11 (6.29%) of gastrointestinal issues (stomach upset, diarrhea, and vomiting), 13 (7.43%) of neuromuscular issues (muscle cramps, spasm, and pain), 13 (7.43%) of cough, 10 (5.71%) of persistent headache, 3 (1.71%) of fever, and 12 (6.86%) of cardiac-related issues were identified. CONCLUSIONS: The AERs associated with SA has been described. Though the MAUDE database is not an exact, wholesome and reliable source to identify the potential AER, currently, it is the only available source of AERs associated with SA use. The nature of AERs with the use of SA and its potential pathogenesis and implications has been discussed. PMID- 26888234 TI - To evaluate the accuracy of various dental parameters used for the gender determination in Nagpur District population. AB - CONTEXT: Gender determination is considered an important step in reconstructing the biological profile of unknown individuals from the forensic context. Assessment of sex differences from human remains will be of immense help as it would narrow down fields of search to 50 %. AIMS: To evaluate the accuracy of various dental parameters used for the gender determination. SETTINGS AND DESIGN: The aim of the present study was to investigate the accuracy of various methods employed in gender determination or personal identification such as mesiodistal width of molars, mesiodistal width of canine, mandibular and maxillary canine index in age group of 15 to 65 years. METHODS AND MATERIAL: A total of 200 patients were selected comprising of both the genders in the age group of 15-65 years belonging to various parts of Nagpur. The mesiodistal crown width of mandibular and maxillary permanent molar and canine teeth and the intercanine distance was measured and the values were noted. STATISTICAL ANALYSIS USED: the data was analysed using SPSS 18 software. RESULTS: The mean of mesio distal width of maxillary and mandibular molar in males and females is suggestive of gender dimorphism in maxillary molars which was statistically significant.The maxillary inter-canine distance was greater in males and was statistically significant. CONCLUSIONS: The dental parameters can be used as a tool for accurate gender determination in forensic investigations. PMID- 26888236 TI - Influence of calcium hydroxide dressing and two irrigants on the filling of artificial lateral canals. AB - CONTEXT: This study was carried out on the assumption that calcium hydroxide [Ca(OH) 2 ] dressing and irrigants may influence the obturation of lateral canals. AIMS: To evaluate the influence of 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) gel and Ca(OH) 2 on the filling of artificial lateral canals. SETTINGS AND DESIGN: Ex vivo quantitative laboratory study. MATERIALS AND METHODS: Forty-two human mandibular premolars were selected. After cavity access, six lateral canals were performed, two in each root section, one mesial and one on the distal root surface. After preparation, the specimens were randomly divided into four groups: Group I: Under irrigation with 2% CHX and saline solution and with intracanal dressing Ca(OH) 2 paste; Group II: The same preparation as Group I, but without Ca(OH) 2 ; Group III: Under irrigation with 2.5% NaOCl without Ca(OH) 2 ; and Group IV: The same preparation as Group III, but with Ca(OH) 2 . Two teeth without intracanal dressing were used as negative controls. Lateral condensation technique was performed. Then, digital radiographic images were obtained. STATISTICAL ANALYSIS USED: Data were analyzed using SPSS 17.0, submitted to Kappa (reliability between examiners) and Kruskal Wallis test. RESULTS: No statistical difference was registered between Groups II and III in all root sections (P > 0.05), but it was observed between Groups I and IV (P < 0.05), except on the apical section (P > 0.05). In all sections, the Group I filled more artificial lateral canals than in Group IV. CONCLUSIONS: The irrigants tested had no influence on the filling of artificial lateral canals. Nevertheless, intracanal dressing of Ca(OH) 2 influenced this filling. PMID- 26888237 TI - Assessment of relationship between oral health behavior, oral hygiene and gingival status of dental students. AB - BACKGROUND: The behavior of oral health providers toward their own oral health reflects their understanding of the importance of preventive dental procedures and of improving the oral health of their target population. AIM: This study was done with an aim to assess the relationship between oral health behavior, oral hygiene and gingival status of third and final year dental students from a Dental College in Indore City, India. METHODS: A total of 137 dental students participated in the study. The students were invited to complete the Hiroshima University-Dental Behavioral Inventory (HU-DBI) questionnaire. The HU-DBI questionnaire consisted of twenty polar responses (agree/disagree) regarding oral health-related behavior. In addition, two further questions about the frequency of brushing and flossing were included. Subsequently, oral health examination was conducted to assess plaque and gingival status. Data were analyzed using Chi square test, Independent sample t-test, and Pearson's correlation. The significance level was set at P <= 0.05. RESULT: The results showed that about 66.6% of the students checked their teeth in the mirror after brushing. Only 20.1% of the students reported bleeding from gums. The mean oral heath behavior score (HU-DBI) was 6.47 +/- 2.0. A negative correlation of HU-DBI scores with plaque (r = -0.501) and gingival scores (r = -0.580) was observed. CONCLUSION: Thus, it is concluded that there is a significant relationship between the oral health behavior, oral hygiene, and gingival status of dental students. Dental students with better self-reported oral health behavior had lower plaque and gingival scores indicating a better attitude toward oral health. PMID- 26888238 TI - Adverse events associated with ultrasonic scalers: A manufacturer and user facility device experience database analysis. AB - BACKGROUND: The present study was conducted to determine the frequency and type of adverse events (AEs) associated with ultrasonic scaler reported to the Food and Drug Administration manufacturer and user facility device experience (MAUDE) database. MATERIALS AND METHODS: The authors reviewed the ultrasonic scaler units (USU) related AEs reported to MAUDE from October 1, 1995, to September 31, 2015. Analyses of details collected are presented. RESULTS: MAUDE received a total of 667 unique USU-related AE reports. Of 667 cases, MAUDE classified 628 instances (94.2%) as malfunction 27 (4%) as injurious, 10 (1.5%) as others, and 2 (0.3%) claiming the use of USU as cause of death. Of the 667 cases, 511 (76.6%) were used for endodontic application, and 147 (22%) as scaler applications. In 512 (76.8%) instances, there was separation of the tips, posing danger to patients or users, and 112 (16.8%) instances of overheating, 12 (1.8%) instances of breakage, and electrical issues in 8 (1.2%) instances. These AE resulted in 19 instances of thermal injury, 2 suspicious deaths, and hearing loss in 3 cases. In 4 cases, patient swallowed broken parts requiring additional medical care. CONCLUSIONS: Use of USU, a Class 2 device without exemption, carries a degree of risk to patient's safety, if not properly used. As of today, MAUDE data is the only reliable source of AE until another database or such study is carried out. Certain AE that has been largely anecdotal, such as hearing loss has been reported in this study. The findings from study reiterate that more in-depth analysis of AE of USU is needed. Until then operator needs to take all precautions to avoid AE when using USU. PMID- 26888239 TI - Callus molding in external and internal distraction of mandible. AB - BACKGROUND: Distraction osteogenesis (DO) emerges to be a promising alternative to the traditional method of bone lengthening, by which a significant skeletal and soft tissue enlargement can be obtained in the hypoplastic area in a short period. Manipulations of the newly created callus (regenerate), during DO or as a single step molding procedure at the end of the distraction process, may be necessary to correct the mandibular position. AIM: To report the efficacy of callus molding (CM) - floating bone concept in the vertical lengthening of ramus by DO and creating a gonial angle in the difficult case of vector selection or surgically induced asymmetry. MATERIALS AND METHODS: Retrospective analysis of patients who underwent DO of mandible followed by CM for correction of mandibular asymmetry at authors centers from 2008 to 2014 formed the study group. Only the mandibular distraction cases were included in the study. After the 5 days of latency period, the mandible was distracted at the rate of 1 mm/day. At the end of DO, CM was completed in the 1-3 weeks before consolidation. CM was done either by removing the lower screws with distractor in place or after removal of distractor based on case selection. Secondary maxillary correction by Le Fort I osteotomy using bone graft and further occlusion is corrected by postorthodontics if necessary. Splints were used during CM for predetermined occlusion. In all the cases, postoperative intermaxillary fixation was maintained for 8 weeks for stable ossification of the callus. RESULTS: The study group consist of four and five cases of external and internal distraction, respectively. Of the 9 patients who underwent DO, 6 were females and 3 were males. The mean age of the population ranged from 10 to 21 years with a mean age of 18 years. The average distracted length of the mandible was 23.55 mm ranging from 20 to 26 mm with the standard deviation of 1.95. The mean deviation of the mandible (crossbite) at the end of distraction was around 8.23 mm ranging from 5 to 12 mm with the standard deviation of 2.17. Of the total 9 cases, only in 3 cases CM is done during DO and the rest 6 cases the CM is done after removal of the distractor. Secondary maxillary correction by Le Fort I osteotomy was done for 4 cases, and postorthodontic correction was done in 3 cases. In all the 9 cases, 100% results (as assessed clinically and radiographically) achieved with the creation of perfect gonial angle. CONCLUSIONS: CM plays a crucial role in those cases where proper vector orientation is hindered because of anatomical difficulty for osteotomy cuts and parallel fixation of the distractor to ramus resulting in cross-bite with deviation toward the undistracted side. Manipulation of the regenerates would provide a precise achievement of gonial angle, minimizing the need for secondary corrections, and diminishing treatment duration and costs. PMID- 26888240 TI - Comparison of semilunar coronally advanced flap alone and in combination with button technique in the treatment of Miller's Class I and II gingival recessions: A pilot study. AB - BACKGROUND: Gingival recession (GR) is one of the most common esthetic and functional concerns associated with periodontal disease. A variety of surgical procedures has been introduced to the field of cosmetic periodontology for the treatment of GR. AIM: To evaluate and compare the clinical outcome of semilunar coronally advanced flap (SCAF) with and without button technique in the treatment of Miller's Class I and II GRs. STUDY DESIGN: A total of 12 subjects with bilateral single Miller's Class I and II recession were selected for the study. Split mouth design was used. MATERIALS AND METHODS: Surgical sites were randomly divided into test and control groups. In control sites, SCAF alone was done whereas in test site, a combination of SCAF and button technique was performed. The clinical parameters including GR, periodontal pocket depth, clinical attachment level (CAL), and width of keratinized gingiva were recorded at baseline and 6 months postsurgery. Data so collected were put to statistical analysis. STATISTICAL ANALYSIS: Student's t-test was used to find significance of parameters between baseline and 6 months. For inter-group comparisons paired t test was performed. RESULTS: Statistically significant improvements were recorded in both groups from baseline to 6 months. Inter-group comparison yielded statistically significant differences in GR and CAL in favor of test group. CONCLUSION: Combination of SCAF and button technique resulted in statistically significant improvements in clinical parameters as compared to SCAF alone. Future clinical studies with much larger sample size and longer follow-up periods are warranted. PMID- 26888241 TI - To comparatively evaluate the antimicrobial efficacy of chlorhexidine, nisin and linezolid as an intracanal medicament on Enterococcus faecalis: An in vitro study. AB - AIM: The present study evaluated the antimicrobial efficacy of Chlorhexidine, Nisin and Linezolid and a control group (Normal saline ) against Enterococcus faecalis (EF). METHODS: Human single rooted premolars with type I canal anatomy were instrumented with ProTaper using NaOCl as an irrigant. Supension of EF was inoculated into each root specimen and incubated. The medicaments were syringed into each root and incubated. After 24 hours, 8 samples per group (among the 4 groups) were retrieved. A hole was drilled on each root, and the dentinal shavings obtained were allowed to fall in brain-heart infusion (BHI) broth. Dilutions from the broth were plated and spread over blood agar. Colony-forming units (CFU) of EF was counted. The procedure was repeated after 72 hrs and 1 week. RESULTS: In group Nisin, the mean CFU was 10.6250 at 24 hrs, 6.6250 at 72 hrs and 6.2500 after 1 week respectively (statistically significant). In group Chlorhexidine, mean CFU was found to be the lowest of 10.5000 at 24 hrs, with further gradual increase to 13.7500 at 72 hrs and further increase to 15.8750 by 1 week. Similarly, in group linezolid , the mean CFU was found to decrease from 49.0000 at 24 hrs to 29.8750 at 72 hrs and then increase to 34.8750 in 1 week. PMID- 26888242 TI - Comparison of diagnostic accuracy of root perforation, external resorption and fractures using cone-beam computed tomography, panoramic radiography and conventional & digital periapical radiography. AB - CONTEXT: Some radicular changes are challenging for clinicians to diagnose, such as of root perforations, external root resorption (ERR), and vertical root fractures (VRFs). This study aims to facilitate it by comparing the diagnostic accuracy of cone-beam computed tomography (CBCT), orthopantomography, and conventional and digital periapical radiography (DPR) in the diagnosis of such problems. Is it worth doing CBCT despite the radiation dose? AIMS: To evaluate and compare the diagnostic accuracy of CBCT, panoramic radiography, and conventional and DPR in the diagnosis of root perforation (RP), ERR, and VRF. MATERIALS AND METHODS: The sample consisted of 40 extracted human teeth and 10 macerated human mandibles. RPs were performed using diamond burs, ERRs using spherical carbide burs, and RFs using a universal machine EMIC-DL 1000. The images were evaluated by 6 dentomaxillofacial radiologists. RESULTS: Receiver operating characteristic (ROC) revealed that CBCT showed the highest area under the ROC curve (Az) values for RP, ERR, and VRF (0.903, 0.950, and 0.849, respectively). The worst Az values for RP, ERR, and VRF (0.718, 0.494, and 0.611, respectively) were for panoramic radiography. CONCLUSIONS: CBCT showed the best results in the diagnosis of ERR and VRF. The diagnosis of ERR was the least accurate, panoramic radiography being not appropriate for its diagnosis. CBCT and conventional periapical radiography obtained similar results for the evaluation of RP. So for, RP indicate the conventional periapical radiography because CBCT has a higher radiation dose. PMID- 26888243 TI - Histological analysis of the biocompatibility of calcium hydroxide associated with a new vehicle. AB - BACKGROUND: Several substances have been researched to act as vehicles associated with calcium hydroxide. The specific type of vehicle is directly related to the effectiveness of the ionic dissociation, antimicrobial action, and biocompatibility of this medication. AIM: To make a histological evaluation of the biocompatibility of calcium hydroxide associated with a new vehicle (triethanolamine), compared with polyethylene glycol, saline solution, and olive oil. MATERIALS AND METHODS: Fifty mice of guinea pig species were randomly divided into five groups (n = 10) according to each vehicle used--Group 1: calcium hydroxide, Group 2: triethanolamine, Group 3: polyethylene glycol, Group 4: saline solution, and Group 5: olive oil--and further divided into subgroups according to the two analysis periods--(a) 30 and (b) 90 days. Teflon carriers filled with the evaluated substances were placed in standardized bone cavities in the anterior mandible region. The animals were euthanized to perform a histological analysis after the time periods analyzed. RESULTS: In 30 days, specimens from Groups 1, 3, and 5 showed a very pronounced inflammatory response. Specimens from Group 2 showed an inflammatory reaction ranging from mild to severe, with rapid resorption of the material and progressive advancement of osteoid tissue into the teflon carriers. Specimens from Group 4 showed a moderate inflammatory reaction. In 90 days, specimens from Group 1 showed a very pronounced fibrous replacement. In regard to Group 2 specimens, the tested material was solubilized and replaced by newly formed bone tissue. For Groups 3 and 5 specimens, the inflammatory reaction went from acute to moderate. In relation to Group 4 specimens, an organized bone formation process was observed. CONCLUSIONS: Specimens from Group 2 showed higher biocompatibility, especially as compared with the specimens from Groups 3 and 5. PMID- 26888244 TI - Maxillary plexiform ameloblastoma showing basaloid differentiation: Report of a rare case with review of literature. AB - Ameloblastoma is a benign, locally aggressive tumor originating from the odontogenic epithelium. It manifests as a slow growing swelling, causing expansion of the jaw bones. Radiologically, it presents as a unilocular or multilocular radiolucency exhibiting a characteristic soap bubble or honeycomb appearance. Ameloblastoma exhibits several histologic patterns of which basal cell variant is a rare entity. The present case report is that of a maxillary ameloblastoma exhibiting a basaloid differentiation that may put one in the mind of a basaloid squamous cell carcinoma or a basal cell carcinoma. Confirmation of such rare variants should be done not only based on histopathology but with the help of supplemental immunohistochemical analysis. The present case report helps in exposing a rare variant of ameloblastoma and emphasizes the role of advanced diagnostic aids such as immunohistochemistry in establishing the diagnosis. PMID- 26888245 TI - Impacted stapler pin in fractured maxillary central incisor with open apex: Advanced endodontic management using biodentine as innovative apical matrix. AB - The presence of foreign objects in the pulp chamber of fractured permanent teeth is a rare phenomenon and often diagnosed accidently .These foreign bodies are most commonly self inflicted by young patients and remain impacted within the pulp canal thereby acting as potential source of infection and painful conditions. In the present case report, we present successful endodontic management of stapler pin lodged in fractured maxillary central incisor with challenge of open apex in young patient using biodentine as a novel apical matrix. PMID- 26888246 TI - Extragnathic and gnathic odontome. AB - This is a very rare case report of a multiple odontome involving the upper jaws, lower jaws and an extragnathic site. A thirty seven year-old male complained of missing teeth in his left upper and lower jaw since childhood. Radiographic examination revealed multiple calcified teeth like structures in the left side of the patient's maxilla, mandible and mastoid region of skull base. We arrived at the diagnosis of compound odontome. Patient was otherwise systemically normal and with good health. He underwent surgical enucleation of the jaw odontome while the extragnathic odontome was left under observation. This rare case report proves that the embryonic dental cells might migrate to the primordium of the Rathke's pouch and further might be carried towards the site of the developing cranial base region. PMID- 26888247 TI - Verrucous hemangioma of the oral cavity: A rare diagnostic dilemma. AB - Verrucous hemangioma (VH) is an uncommon, congenital, vascular malformation that involves dermis and subcutaneous connective tissue of skin. VH lesions are initially present at birth, and therefore, the diagnosis in the elderly may be difficult. Review of literature reveals that VH lesions are commonly located unilaterally on the lower extremities. VH may clinically present as keratotic, papular, nodular, or plaque-like lesions that are reddish-blue in color. VH does not resolve spontaneously and has a tendency to relapse. The diagnosis of VH is generally done on the basis of histopathology. Early diagnosis is important to get a better cosmetic result. VH requires a large, deep excision to avoid recurrence because of frequent extension into subcutaneous fat planes. Intra-oral lesions of VH have rarely been reported in the literature. We present an extremely rare case of VH occurring in the retromolar triangle area of oral cavity. PMID- 26888248 TI - In-office technique to fabricate triple tray. AB - Dual arch impressions have been in use for many years. Five in-office techniques for fabrication of the tray have been suggested, in case the manufactured (stock) tray is not available to the clinician. The design consists of two parts of the tray (the plastic frame and lattice). Five types of materials for the lattice have been described. The indications, advantages, and disadvantages of the techniques together with an appraisal of the five different lattice materials have been described. Overall the techniques are simple and require materials that are easily available. It does not take much time and can be used to attain efficient results in case the stock tray is not available in the operatory. PMID- 26888249 TI - Platform switching: Hype or reality? PMID- 26888250 TI - Response to editorial on research publication and reward mechanism. PMID- 26888251 TI - beta-Adrenergic receptor agonist, compound 49b, inhibits TLR4 signaling pathway in diabetic retina. AB - Diabetic retinopathy has recently become associated with complications similar to chronic inflammatory diseases. Although it is clear that tumor necrosis factor alpha is increased in diabetes, the role of innate immunity is only recently being investigated. As such, we hypothesized that diabetes would increase Toll like receptor 4 (TLR4) signaling, which could be inhibited by a beta-adrenergic receptor agonist (Compound 49b) previously shown to have anti-inflammatory actions. In order to investigate beta-adrenergic receptor signaling and TLR4 in the diabetic retina, streptozotocin-injected diabetic mice, as well as human primary retinal endothelial cells (RECs) and rat retinal Muller cells (rMC-1) exposed to high glucose (25 mM), were treated with a novel beta-adrenergic receptor agonist, Compound 49b (50 nM), or phosphate-buffered saline (control). TLR4 and its downstream signaling partners (MyD88, IL-1 receptor-associated kinase 1, TNF receptor-associated factor 6 and total and phosphorylated nuclear factor-kappaB) were examined. In addition, we assessed high-mobility group box 1 (HMGB1) protein levels. Our data showed that diabetes or high-glucose culture conditions significantly increased TLR4 and downstream signaling partners. Compound 49b was able to significantly reduce TLR4 and related molecules in the diabetic animal and retinal cells. HMGB1 was significantly increased in RECs and Muller cells grown in high-glucose culture conditions, which was subsequently reduced with Compound 49b treatment. Our findings suggest that high glucose may increase HMGB1 levels that lead to increased TLR4 signaling. Compound 49b significantly inhibited this pathway, providing a potential mechanism for its protective actions. PMID- 26888252 TI - A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function. AB - Macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor (cA-SR) that recognizes and phagocytoses a wide variety of pathogens. Most cA-SRs that contain a C-terminal scavenger receptor cysteine-rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro-inflammatory signaling is less clear. The discovery of a naturally occurring transcript variant lacking the SRCR domain, MARCOII, provided the opportunity to study the role of the SRCR domain of MARCO. We tested whether the SRCR domain is required for ligand binding, promoting downstream signaling and enhancing cellular adhesion. Unlike cells expressing full-length MARCO, ligand binding was abolished in MARCOII-expressing cells. Furthermore, co-expression of MARCO and MARCOII impaired phagocytic function, indicating that MARCOII acts as a dominant-negative variant. Unlike MARCO, expression of MARCOII did not enhance Toll-like receptor 2 (TLR2)-mediated pro-inflammatory signaling in response to bacterial stimulation. MARCO-expressing cells were more adherent and exhibited a dendritic-like phenotype, whereas MARCOII-expressing cells were less adherent and did not exhibit changes in morphology. These data suggest the SRCR domain of MARCO is the key domain in modulating ligand binding, enhancing downstream pro-inflammatory signaling and MARCO-mediated cellular adhesion. PMID- 26888254 TI - Biodegradation of DDT by Stenotrophomonas sp. DDT-1: Characterization and genome functional analysis. AB - A novel bacterium capable of utilizing 1,1,1-trichloro-2,2-bis(p chlorophenyl)ethane (DDT) as the sole carbon and energy source was isolated from a contaminated soil which was identified as Stenotrophomonas sp. DDT-1 based on morphological characteristics, BIOLOG GN2 microplate profile, and 16S rDNA phylogeny. Genome sequencing and functional annotation of the isolate DDT-1 showed a 4,514,569 bp genome size, 66.92% GC content, 4,033 protein-coding genes, and 76 RNA genes including 8 rRNA genes. Totally, 2,807 protein-coding genes were assigned to Clusters of Orthologous Groups (COGs), and 1,601 protein-coding genes were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The degradation half-lives of DDT increased with substrate concentration from 0.1 to 10.0 mg/l, whereas decreased with temperature from 15 degrees C to 35 degrees C. Neutral condition was the most favorable for DDT biodegradation. Based on genome annotation of DDT degradation genes and the metabolites detected by GC-MS, a mineralization pathway was proposed for DDT biodegradation in which it was orderly converted into DDE/DDD, DDMU, DDOH, and DDA via dechlorination, hydroxylation, and carboxylation, and ultimately mineralized to carbon dioxide. The results indicate that the isolate DDT-1 is a promising bacterial resource for the removal or detoxification of DDT residues in the environment. PMID- 26888253 TI - Association of Anaesthetists of Great Britain and Ireland: Safe vascular access 2016. AB - Safe vascular access is integral to anaesthetic and critical care practice, but procedures are a frequent source of patient adverse events. Ensuring safe and effective approaches to vascular catheter insertion should be a priority for all practitioners. New technology such as ultrasound and other imaging has increased the number of tools available. This guidance was created using review of current practice and literature, as well as expert opinion. The result is a consensus document which provides practical advice on the safe insertion and removal of vascular access devices. PMID- 26888255 TI - Treasury will take "incredibly dim view" of L2.3bn NHS overspend. PMID- 26888256 TI - Novel genetic predictors of venous thromboembolism risk in African Americans. AB - Venous thromboembolism (VTE) is the third most common life-threatening cardiovascular condition in the United States, with African Americans (AAs) having a 30% to 60% higher incidence compared with other ethnicities. The mechanisms underlying population differences in the risk of VTE are poorly understood. We conducted the first genome-wide association study in AAs, comprising 578 subjects, followed by replication of highly significant findings in an independent cohort of 159 AA subjects. Logistic regression was used to estimate the association between genetic variants and VTE risk. Through bioinformatics analysis of the top signals, we identified expression quantitative trait loci (eQTLs) in whole blood and investigated the messenger RNA expression differences in VTE cases and controls. We identified and replicated single nucleotide polymorphisms on chromosome 20 (rs2144940, rs2567617, and rs1998081) that increased risk of VTE by 2.3-fold (P< 6 * 10(-7)). These risk variants were found in higher frequency among populations of African descent (>20%) compared with other ethnic groups (<10%). We demonstrate that SNPs on chromosome 20 are cis-eQTLs for thrombomodulin (THBD), and the expression of THBD is lower among VTE cases compared with controls (P= 9.87 * 10(-6)). We have identified novel polymorphisms associated with increased risk of VTE in AAs. These polymorphisms are predominantly found among populations of African descent and are associated with THBD gene expression. Our findings provide new molecular insight into a mechanism regulating VTE susceptibility and identify common genetic variants that increase the risk of VTE in AAs, a population disproportionately affected by this disease. PMID- 26888257 TI - Galectin-1 drives lymphoma CD20 immunotherapy resistance: validation of a preclinical system to identify resistance mechanisms. AB - Non-Hodgkin lymphoma (NHL) is the most commonly diagnosed hematologic cancer of adults in the United States, with the vast majority of NHLs deriving from malignant B lymphocytes that express cell surface CD20. CD20 immunotherapy (rituximab) is widely used to treat NHL, even though the initial effectiveness of rituximab varies widely among patients and typically wanes over time. The mechanisms through which lymphomas initially resist or gain resistance to immunotherapy are not well established. To address this, a preclinical mouse model system was developed to comprehensively identify lymphoma transcriptomic changes that confer resistance to CD20 immunotherapy. The generation of spontaneous primary and familial lymphomas revealed that sensitivity to CD20 immunotherapy was not regulated by differences in CD20 expression, prior exposure to CD20 immunotherapy, or serial in vivo passage. An unbiased forward exome screen of these primary lymphomas was used to validate the utility of this expansive lymphoma cohort, which revealed that increased lymphoma galectin-1 (Gal 1) expression strongly correlated with resistance to immunotherapy. Genetically induced lymphoma Gal-1 expression ablated antibody-dependent lymphoma phagocytosis in vitro and lymphoma sensitivity to CD20 immunotherapy in vivo. Human NHLs also express elevated Gal-1 compared with nonmalignant lymphocytes, demonstrating the ability of this preclinical model system to identify molecular targets that could be relevant to human therapy. This study therefore established a powerful preclinical model system that permits the comprehensive identification of the dynamic lymphoma molecular network that drives resistance to immunotherapy. PMID- 26888259 TI - Interfacial Atomic Structure of Twisted Few-Layer Graphene. AB - A twist in bi- or few-layer graphene breaks the local symmetry, introducing a number of intriguing physical properties such as opening new bandgaps. Therefore, determining the twisted atomic structure is critical to understanding and controlling the functional properties of graphene. Combining low-angle annular dark-field electron microscopy with image simulations, we directly determine the atomic structure of twisted few-layer graphene in terms of a moire superstructure which is parameterized by a single twist angle and lattice constant. This method is shown to be a powerful tool for accurately determining the atomic structure of two-dimensional materials such as graphene, even in the presence of experimental errors. Using coincidence-site-lattice and displacement-shift-complete theories, we show that the in-plane translation state between layers is not a significant structure parameter, explaining why the present method is adequate not only for bilayer graphene but also a few-layered twisted graphene. PMID- 26888260 TI - Comparison of two Medication Therapy Management Practice Models on Return on Investment. AB - OBJECTIVE: To compare the return on investment (ROI) of an integrated practice model versus a "hub and spoke" practice model of pharmacist provided medication therapy management (MTM). METHODS: A cohort retrospective analysis of MTM claims billed in 76 pharmacies in North Carolina in the 2010 hub and spoke practice model and the 2012 "integrated" practice model were analyzed to calculate the ROI. RESULTS: In 2010, 4089 patients received an MTM resulting in 8757 claims in the hub and spoke model. In 2012, 4896 patients received an MTM resulting in 13 730 claims in the integrated model. In 2010, US$165 897.26 was invested in pharmacist salary and $173 498.00 was received in reimbursement, resulting in an ROI of +US$7600.74 (+4.6%). In 2012, US$280 890.09 was invested in pharmacist salary and US$302 963 was received in reimbursement, resulting in an ROI of +US$22 072.91 or (+7.9%). CONCLUSION: The integrated model of MTM showed an increase in number of claims submitted and in number of patients receiving MTM services, ultimately resulting in a higher ROI. While a higher ROI was evident in the integrated model, both models resulted in positive ROI (1:12-1:21), highlighting that MTM programs can be cost effective with different strategies of execution. PMID- 26888258 TI - Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000. AB - Induction therapy for childhood acute lymphoblastic leukemia (ALL) traditionally includes prednisone; yet, dexamethasone may have higher antileukemic potency, leading to fewer relapses and improved survival. After a 7-day prednisone prephase, 3720 patients enrolled on trial Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Munster (AIEOP-BFM) ALL 2000 were randomly selected to receive either dexamethasone (10 mg/m(2) per day) or prednisone (60 mg/m(2) per day) for 3 weeks plus tapering in induction. The 5 year cumulative incidence of relapse (+/- standard error) was 10.8 +/- 0.7% in the dexamethasone and 15.6 +/- 0.8% in the prednisone group (P < .0001), showing the largest effect on extramedullary relapses. The benefit of dexamethasone was partially counterbalanced by a significantly higher induction-related death rate (2.5% vs 0.9%, P = .00013), resulting in 5-year event-free survival rates of 83.9 +/- 0.9% for dexamethasone and 80.8 +/- 0.9% for prednisone (P = .024). No difference was seen in 5-year overall survival (OS) in the total cohort (dexamethasone, 90.3 +/- 0.7%; prednisone, 90.5 +/- 0.7%). Retrospective analyses of predefined subgroups revealed a significant survival benefit from dexamethasone only for patients with T-cell ALL and good response to the prednisone prephase (prednisone good-response [PGR]) (dexamethasone, 91.4 +/- 2.4%; prednisone, 82.6 +/- 3.2%; P = .036). In patients with precursor B-cell ALL and PGR, survival after relapse was found to be significantly worse if patients were previously assigned to the dexamethasone arm. We conclude that, for patients with PGR in the large subgroup of precursor B-cell ALL, dexamethasone especially reduced the incidence of better salvageable relapses, resulting in inferior survival after relapse. This explains the lack of benefit from dexamethasone in overall survival that we observed in the total cohort except in the subset of T cell ALL patients with PGR. This trial was registered at www.clinicaltrials.gov (BFM: NCT00430118, AIEOP: NCT00613457). PMID- 26888261 TI - The Impact of Clinical Pharmacist Integration on a Collaborative Interdisciplinary Diabetes Management Team. AB - OBJECTIVE: The national initiative, Project IMProving America's Communities Together (IMPACT): Diabetes, was intended to scale a proven American Pharmacists Association (APhA) Foundation process model, which integrates pharmacists on the collaborative health-care team, in communities greatly affected by diabetes to improve key indicators of diabetes. This article discusses the results from 1 community in Mississippi. METHODS: This national prospective study followed patients with a hemoglobin A1c (HbA1c) >7% from September 2011 to January 2013. Pharmacists collaborated with providers and other health-care professionals to provide medication therapy management services for a minimum of 3 visits. Outcome measures included HbA1c, systolic and diastolic blood pressure (SBP and DBP), fasting cholesterol panel, body mass index (BMI), influenza vaccine and smoking status, and foot and eye examination dates. RESULTS: At this site, there were statistically significant outcomes including mean HbA1c decrease of 1.2% in SBP and DBP of 8.3 mm Hg and 3.5 mm Hg, respectively, and reduction in low-density lipoprotein of 16.6 mg/dL, all of which were greater improvements compared to overall results from combined sites. CONCLUSION: Patients in this community who received care from the collaborative team, including a pharmacist, had improvement in most key indicators of diabetes, with a clinically significant reduction in HbA1c. PMID- 26888263 TI - Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection. AB - African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors. PMID- 26888262 TI - New England harbor seal H3N8 influenza virus retains avian-like receptor specificity. AB - An influenza H3N8 virus, carrying mammalian adaptation mutations, was isolated from New England harbor seals in 2011. We sought to assess the risk of its human transmissibility using two complementary approaches. First, we tested the binding of recombinant hemagglutinin (HA) proteins of seal H3N8 and human-adapted H3N2 viruses to respiratory tissues of humans and ferrets. For human tissues, we observed strong tendency of the seal H3 to bind to lung alveoli, which was in direct contrast to the human-adapted H3 that bound mainly to the trachea. This staining pattern was also consistent in ferrets, the primary animal model for human influenza pathogenesis. Second, we compared the binding of the recombinant HAs to a library of 610 glycans. In contrast to the human H3, which bound almost exclusively to alpha-2,6 sialylated glycans, the seal H3 bound preferentially to alpha-2,3 sialylated glycans. Additionally, the seal H3N8 virus replicated in human lung carcinoma cells. Our data suggest that the seal H3N8 virus has retained its avian-like receptor binding specificity, but could potentially establish infection in human lungs. PMID- 26888264 TI - Model-based analyses of whole-genome data reveal a complex evolutionary history involving archaic introgression in Central African Pygmies. AB - Comparisons of whole-genome sequences from ancient and contemporary samples have pointed to several instances of archaic admixture through interbreeding between the ancestors of modern non-Africans and now extinct hominids such as Neanderthals and Denisovans. One implication of these findings is that some adaptive features in contemporary humans may have entered the population via gene flow with archaic forms in Eurasia. Within Africa, fossil evidence suggests that anatomically modern humans (AMH) and various archaic forms coexisted for much of the last 200,000 yr; however, the absence of ancient DNA in Africa has limited our ability to make a direct comparison between archaic and modern human genomes. Here, we use statistical inference based on high coverage whole-genome data (greater than 60*) from contemporary African Pygmy hunter-gatherers as an alternative means to study the evolutionary history of the genus Homo. Using whole-genome simulations that consider demographic histories that include both isolation and gene flow with neighboring farming populations, our inference method rejects the hypothesis that the ancestors of AMH were genetically isolated in Africa, thus providing the first whole genome-level evidence of African archaic admixture. Our inferences also suggest a complex human evolutionary history in Africa, which involves at least a single admixture event from an unknown archaic population into the ancestors of AMH, likely within the last 30,000 yr. PMID- 26888266 TI - Silent Cerebral Ischemic Lesions After Catheter Ablation of Atrial Fibrillation in Patients on 5 Types of Periprocedural Oral Anticoagulation - Predictors of Diffusion-Weighted Imaging-Positive Lesions and Follow-up Magnetic Resonance Imaging. AB - BACKGROUND: The aim of this study was to identify the predictors of silent cerebral ischemic lesions (SCIL) after catheter ablation of atrial fibrillation (AF) and to determine whether SCIL develop into cerebral infarcts in patients with 5 types of oral anticoagulants (OAC). METHODS AND RESULTS: We retrospectively studied 286 consecutive patients (median, 67 years; 208 male; paroxysmal/persistent/long-standing persistent AF [LSP-AF], 147/90/49) who received periprocedural OAC and underwent MRI after the procedure. Warfarin (n=46) was continued, while dabigatran (n=47), rivaroxaban (n=89), apixaban (n=87), and edoxaban (n=17) were discontinued on the day of the procedure. I.v. heparin was infused to maintain an activated clotting time of 300-350 s during the procedure. Fifty-eight SCIL in 40 patients (14.0%) were identified on diffusion-weighted MRI. On multivariate logistic analysis, LSP-AF and dabigatran use were significant positive predictors of SCIL (OR, 2.912 and 2.287; P=0.006 and 0.042, respectively). Among 34 patients with 49 SCIL undergoing follow-up MRI, 45 (91.8%) of the lesions disappeared and 4 lesions developed into chronic cerebral infarcts. The SCIL with development into infarcts had a larger lesion diameter than those without (median, 6.55 mm vs. 4.2 mm; P=0.002). CONCLUSIONS: LSP-AF and dabigatran use were independent risk factors for post-ablation SCIL in patients with uninterrupted warfarin and interrupted non-vitamin K antagonist OAC, but the majority of SCIL disappeared. PMID- 26888268 TI - [Raise awareness of IgG4 relative ocular disease]. AB - Purpose IgG4-related ocular disease is a chronic systemic disease with lymphocyte abnormal. The lacrimal glands, extraocular muscles and infraorbital nerve were often involved which was often the first symptom of systemic disease. While ophthalmologists did not know this disease well. They usually misdiagnosed it as idiopathic inflammatory pseudotumor, thyroid-associated ophthalmopathy etc, which resulted in delayed treatments. Here pathogenesis, clinical features and treatment methods of IgG4-relative ocular disease were described in order to improve awareness of this ocular disease, reduce clinical misdiagnosis, improve disease prognosis and standardized treatment. As the incidence of this disease increased in recent years, it is very necessary to improve awareness of the disease for ophthalmologists. PMID- 26888265 TI - Alternative splicing modulated by genetic variants demonstrates accelerated evolution regulated by highly conserved proteins. AB - Identification of functional genetic variants and elucidation of their regulatory mechanisms represent significant challenges of the post-genomic era. A poorly understood topic is the involvement of genetic variants in mediating post transcriptional RNA processing, including alternative splicing. Thus far, little is known about the genomic, evolutionary, and regulatory features of genetically modulated alternative splicing (GMAS). Here, we systematically identified intronic tag variants for genetic modulation of alternative splicing using RNA seq data specific to cellular compartments. Combined with our previous method that identifies exonic tags for GMAS, this study yielded 622 GMAS exons. We observed that GMAS events are highly cell type independent, indicating that splicing-altering genetic variants could have widespread function across cell types. Interestingly, GMAS genes, exons, and single-nucleotide variants (SNVs) all demonstrated positive selection or accelerated evolution in primates. We predicted that GMAS SNVs often alter binding of splicing factors, with SRSF1 affecting the most GMAS events and demonstrating global allelic binding bias. However, in contrast to their GMAS targets, the predicted splicing factors are more conserved than expected, suggesting that cis-regulatory variation is the major driving force of splicing evolution. Moreover, GMAS-related splicing factors had stronger consensus motifs than expected, consistent with their susceptibility to SNV disruption. Intriguingly, GMAS SNVs in general do not alter the strongest consensus position of the splicing factor motif, except the more than 100 GMAS SNVs in linkage disequilibrium with polymorphisms reported by genome-wide association studies. Our study reports many GMAS events and enables a better understanding of the evolutionary and regulatory features of this phenomenon. PMID- 26888269 TI - [The role of laser photocoagulation in the anti-vascular endothelial growth factor therapy era]. AB - Anti-vascular endothelial growth factor (VEGF) therapy has recently become the first-line treatment for wet age related macular degeneration, macular edema secondary to diabetic retinopathy and retinal vein occlusion, retinopathy of prematurity and neovascular glaucoma. It is worth thinking about whether laser photocoagulation still has its therapeutic value in these diseases. The purpose of this article is to discuss the role of laser photocoagulation in the anti-VEGF therapy era. And the article also discussed the combined treatment strategy in order to avoid clinical errors and to provide a new insight for prevention and treatment of ocular neovascular disease in the future. PMID- 26888267 TI - Decreased Defibrillation Threshold and Minimized Myocardial Damage With Left Axilla Implantable Cardioverter Defibrillator Implantation. AB - BACKGROUND: To reduce myocardial damage caused by implantable cardioverter defibrillator (ICD) shock, the left axilla was studied as an alternative pulse generator implantation site, and compared with the traditional implantation site, the left anterior chest. METHODS AND RESULTS: Computer simulation was used to study the defibrillation conduction pattern and estimate the simulated defibrillation threshold (DFT) and myocardial damage when pulse generators were placed in the left axilla and left anterior chest, respectively; pulse generators were also newly implanted in the left axilla (n=30) and anterior chest (n=40) to compare the corresponding DFT. On simulation, when ICD generators were implanted in the left axilla, compared with the left anterior chest, the whole heart may be defibrillated with a lower defibrillation energy (left axilla 6.4 J vs. left anterior chest 12.0 J) and thus the proportion of cardiac myocardial damage may be reduced (2.1 vs. 4.2%). Clinically, ventricular fibrillation was successfully terminated with a defibrillation output <=5 J in 86.7% (26/30) of the left axillary group, and in 27.5% (11/40) of the left anterior group (P<0.001). CONCLUSIONS: Clinically and theoretically, the left axilla was shown to be an improved ICD implantation site that may reduce DFT and lessen myocardial damage due to shock. Lower DFT also facilitates less myocardial damage, as a result of the lower shock required. PMID- 26888270 TI - [Ocular syndromes in patients with neurobrucellosis]. AB - OBJECTIVE: To investigate the clinical features of ocular syndromes in patients with neurobrucellosis. METHOD: This is a retrospective series case study. The clinical data of 5 patients with neurobrucellosis, who were treated in Department of Neurology, Beijing Tongren Hospital, Captical Medical Uinversity, from May 2009 to January 2015, were collected. Their epidemiological information, clinical manifestation, laboratory and radiologic examination, therapy and prognosis were analyzed. RESULTS: Among the five patients, there were 3 males and 2 females, and their ages ranged from 20 to 67 years. The median age was 25 years. All patients had ever exposed to sheep. 1 patient lived close to a slaughterhouse and 2 patients lived in epidemic areas of brucellosis. 5 patients presented with binocular vision loss, 8 eyes with fundus edema, 3 patients with ophthalmoplegia;4 patients with fever,4 patients with headache,3 patients with neck stiffness,1 patient with movement and sensation disorders. Cerebrospinal fluid (CSF) pressure elevated, white cell number and protein increased with glucose reduction were detected respectively in 3 cases. While, CSF chloride decreased in 2 cases. Serum agglutination test for brucella was positive in 5 patients. Serum brucella culture was positive in 1 patient and CSF brucella culture was positive in 1 patient. Brain magnetic resonance imaging (MRI) showed that the optic nerve was involved in 3 patients,the meninges were involved in 1 patient and the brain white matter was involved in 1 patient. The combination of rifamycin, tetracycline, ceftriaxone sodium or quinolone were given to all patients and showed appreciated effects. CONCLUSIONS: The clinical features of ocular syndromes are atypical in patients with neurobrucellosis. Vision loss and ophthalmoplegia are more common to be seen. Neurobrucellosis should be considered when patients with ocular signs and other system symptoms without a definite diagnosis. PMID- 26888271 TI - [Relationship between the levels and variation of CXCL12, PDGF, CXCL14 in cerebrospinal fluid of optic neuritis and neuromyelitis optica]. AB - OBJECTIVE: To explore the predictive value of the prognosis and outcome for optic neuritis (ON) and neuromyelitis optica (NMO) by investigating the levels and variation of CXCL12, PDGF and CXCL14 in CSF of patients with ON and NMO. METHODS: Retrospective study. Thirty-five patients with ON, 10 patients with NMO and 10 patients with cerebral venous sinus thrombosis (CVST) were scheduled in the research unit from September 2012 to September 2013 in Neuro-Ophthalmology Department of PLA General Hospital. Clinical data and cerebrospinal fluid (CSF) parameters were collected. CXCL12, PDGF and CXCL14 concentrations were measured in CSF using enzyme linked immunosorbent assay (ELISA). The CXCL12, PDGF and CXCL14 levels in CSF were compared by using ANOVA in different diseases with different phases and recurrent cases found by MRI. Multiple comparisons were used by LSD method. The comparison of positive rate for MRI in ON different phases was used by exact probability. Meanwhile, correlation analysis was conducted between CXCL12, PDGF, CXCL14 and white blood cells (WBC), IgG and protein in CSF. RESULTS: Compared with NMO group (3.69+/-0.35, 2.04+/-0.24, 7.05+/-0.94), the CXCL12, PDGF and CXCL14 levels in CSF were higher in ON (4.39+/-0.51, 2.51+/ 0.39, 8.65+/-1.55) and CVST(4.84+/- 0.49, 2.79+/-0.47, 10.53+/-1.11) group (F=14.593, 10.060, 10.003,P<0.001, <0.001, <0.001), especially the CXCL12, PDGF and CXCL14 levels in CSF of CVST group patients were higher than that in ON group. Among them, the CXCL12 and PDGF levels in CSF were higher in acute phase of ON (4.63+/-0.50, 2.65+/-0.40) and CVST(4.84+/-0.49, 2.79+/-0.47) group than stationary phase of ON (4.13+/-0.39, 2.34+/-0.32) group (F=8.823, 4.906, P=0.001, 0.012). In addition, 28 of 35 ON patients were conducted the cerebral or orbital magnetic resonance imaging (MRI). The result showed that the CXCL12 and PDGF levels in CSF of patients with positive finding in MRI (3.96+/-0.30, 2.23+/-0.16) were higher than those patients with negative finding in MRI (4.64+/-0.42, 2.62+/ 0.42) (t=-4.754, -2.977, all P<0.01). Besides that, there was higher correlation between the CXCL12 level and PDGF in CSF (P<0.01). CONCLUSIONS: Reduced concentration of cytokine that promoted remyelination such as CXCL12 and PDGF in cerebrospinal fluid of the ON and NMO patients may predict a bad myelin regeneration. PMID- 26888272 TI - [Eight cases of cavernous hemangioma of the optic chiasm]. AB - OBJECTIVE: To report the clinical characteristics, neuto-imaging and prognosis of cavernous hemangioma of the optic chiasm. METHODS: Retrospective data analysis was conducted in 8 patients from Beijing Tongren Hospital and Beijing Tiantan Hospital. Patients' clinical characteristics, neuroimaging and prognosis were assessed. RESULTS: There were eight patients aging from 16-58 years old including 3 females and 5 males. The median age was 39.5 years. From the time of onset to diagnosis, the shortest time was 25 days and the longest was 2 years and 4 months. Clinical characteristics of 8 cases were analyzed. Among 8 cases, 3 patients had acute course, 3 patient had chronic course with acute exacerbation and 2 patients had chronic course. All patients presented with decreased visual acuity and/or visual field defect and 3 cases had headache. The most common initial manifestation was decreased visual acuity and/or visual field defect (4 cases). Only 4 cases were diagnosed cavernous hemangioma of the optic chiasm before surgery. The hemangioma was total resected in 6 patients and other two got partly removed. Visual function was improved in 4 cases after surgery. MRI showed mixed signal. CONCLUSIONS: All patients presented decreased visual acuity and/or visual field defect, often accompanied with headache. It can be misdiagnosed at early stage. MRI may be helpful to the diagnosis. Complete resection at early stage may improve the visual function. PMID- 26888273 TI - [Expression of Bcl-2 and Bax on retinal with a rat model for ocular ischemic syndrome]. AB - OBJECTIVE: To tell the difference of Bcl-2 and Bax expression on the retina between the ocular ischemic syndrome group and the sham group. METHODS: Experimental study. To establish the ocular ischemic syndrome model by bilateral common carotid arteries obliteration (BCCAO) in BN rats. Twenty BN rats were divided into two groups randomly: 12 in the model group and 8 in the sham group. In model group, midline incised in the neck and bilateral common carotid artery obliterated. While in the sham group, midline incised in the neck with no obliteration. Pupillary reflex were detected in both groups. After 1 month, rats underwent fundus fluorescein angiography (FFA) examination. Optical coherence tomography (OCT) was used to measure and tell the retina thickness difference in both groups. Expression of Bcl-2 and Bax on rat retina and change of the Bcl 2/Bax ratio were detected by immunohistochemical staining. Chisquare test was used for classification variable, two independent samples T test was used for quantitative data. RESULTS: Compared to the sham group, only 1 eye of BCCAO group maintained its direct pupillary reflex, other eyes of the group appeared either lost or weakened their direct pupillary reflex. However, all rats in the sham group maintained their pupillary reflex. FFA showed that in the BCCAO group, retinal circulation time was significantly longer than it was in the sham group (aterial phase:t=6.19,P<0.01; arteriovenous phase:t=8.24,P<0.01; venous phase:t=2.73,P<0.05). And in the model group, the background choroidal patchy hypofluorescence and typical arterial forward phenomenon in the early phase of arterial time were observed. OCT showed that in the model group, an obvious decrease of the thickness of neuroepithelial layer of retina was observed, which was (195.67+/-8.84) um in the model group and (219.31+/- 6.92) um in the sham group. It had statistically significant difference (P<0.05). Immunohistochemical staining results showed imbalance of Bcl-2, Bax expression on rat retina. Compared with the sham group, expression level of bax which was (5.67+/-0.84) um in the model group was significantly increased (P<0.05) , while it was (2.34 +/- 0.57) um in the sham group. There was no significant difference (P>0.05) in Bcl-2 expression in both groups, which was (5.61+/-0.98) um in the model group and which was (5.63+/-0.88) um in the sham group. And Bcl-2/Bax ratio was observed statistically significant decreased (P<0.05) in the BCCAO group compared with that in the sham group, which was (1.01 +/- 0.23) in the model group, and which was (2.47+/-0.47) in the sham group. CONCLUSIONS: BCCAO of rats lead to the injury of retina function, diminish of retinal thickness, imbalance of Bax and Bcl-2 expression. PMID- 26888274 TI - [Clinical observations of acute-onset endophthalmitis after clear corneal phacoemulsification]. AB - OBJECTIVE: To evaluate the incidence of acute-onset endophthalmitis after clear corneal phacoemulsification and to report its clinical features, microbiology, and therapeutic efficacy. METHODS: It was a retrospective case series study. Medical records were reviewed for all patients diagnosed with acuteonset postoperative endophthalmitis from 2006 through 2013 associated with cataract surgery at Shandong Eye Institute of China. RESULTS: The 8-year frequency of acute-onset endophthalmitis after clear corneal phacoemulsification was 0.13%. The mean time between cataract extraction and endophthalmitis onset was 6 days (median, range 1 to 37 days). Endophthalmitis onset occurred within 7 days in 57.1%. The incidence was significantly higher in summer (0.25%) than in other seasons seasons (F=8.61, P=0.05). The incidence in diabetes was 0.06% , and in non-diabetic patients was 0.16% (F=1.51, P=0.23). There were no significantly difference (F=0.003, P=0.422, ) in the endophthalmitis rates between those with capsular rupture (0.24%)and those without (0.13%). Three of the 21 cases (14.3%) were cured by antibiotic agents only. Antibiotic irrigation of the capsular bag was taken in 8 patients (38.1%). Six patients (28.6%) had both antibiotic irrigation of the capsular bag and intravitreal injection of the antibiotics and the other 4 patients (19.0%) were cured by vitreous surgery. Cultures were positive in 33.3% of cases with aqueous humor samples and in 16.7% of cases with vitreous biopsy. The culture isolates showed Staphylococcus species in 2 eyes, while Pseudomonas paucimobilis, Corynebacterium xerose, Neisseria mucosa and Enterococcus faecalis in 1 eye respectively. Sixteen patients (76.2%) achieved a final visual acuity of 20/40 or better. Five (23.8%) had worse than 20/40 to better than 20/200. No eyes were eviscerated. CONCLUSION: Early recognition and appropriate treatment are the most important factors in the successful management of endophthalmitis. PMID- 26888276 TI - [Research progresses of monoclonal antibodies therapy in neuromyelitis optica]. AB - Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. There is no effective treatment so far. In recent years, monoclonal antibodies (mAbs) have been applied in a number of clinical drug trials and basic researches in NMO therapy due to its specificity and uniformity. Phase I clinical study found that, symptoms significantly improved in some patients after mAbs treatment. This review will expound the therapy classification, mechanism of action and clinical results involving mAbs, and provide reference for the clinical treatments of NMO. PMID- 26888277 TI - [Research status on the epidemiological characteristics of optic neuritis]. AB - Optic neuritis(ON) is one of common neuro-ophthalmologic diseases which cause vision loss in young and middle-aged population. There are obvious differences in the incidence and the epidemiological characteristics among different countries and regions. A number of studies on ON have been carried out at home and abroad. In China, it is still lack of multi-center, prospective, large sample epidemiological studies so far. This paper reviews the epidemiological characteristics of ON through the related domestic and overseas literatures. PMID- 26888275 TI - [Clinical evaluation of a thermodynamic treatment system for meibomian gland dysfunction]. AB - OBJECTIVE: To evaluate the effectiveness and safety of a single thermodynamic treatment system (LipiFlow) for meibomian gland dysfunction (MGD). METHODS: Retrospective series case study. Forty-eight subjects with meibomian gland dysfunction were analyzed before and after 12 minutes LipiFlow system treatment. All subjects were examined before, 4 weeks and 12 weeks after this treatment. Subjective symptoms, lipid layer thickness (LLT), expressible meibomian gland, tear break-up time, meibomian gland assessment and ocular surface staining were measured. Statistical analysis was performed using SPSS 11.5 software. Analysis included those independent sample two-tailed t-tests for comparison of the mean change from baseline to 4 weeks and baseline to 12 weeks after Lipiflow treatment. Statistically significant difference was based on alpha=0.05 (P<0.05). RESULTS: A total of 48 cases completed the 12-week follow-up. MGD patients with LipiFlow treatment had a significant reduction in the Ocular Surface Disease Index (OSDI) scores with 45.36+/-19.34 before treatment, 23.82+/-11.94 at 4 weeks (t=2.009, P=0.035) and 25.66+/-14.12 at 12 weeks (t=1.976 P=0.038). LipiFlow resulted in a higher number of expressible glands from 2.91+/-1.13 (baseline) to 6.27+/-2.37 (4 weeks, t=3.505, P<0.001) and 5.15+/-2.08 (12 weeks, t=2.004, P= 0.027) and change of secretion quality from 6.18+/-2.48 (baseline) to 13.55+/ 3.46 (4 weeks,t=2.698,P=0.005) and 12.67+/-3.41 (12 weeks,t=2.403,P=0.009). In addition, a single thermodynamic treatment increase the LLT from (42.13+/-9.67)nm (baseline) to (59.02+/-16.39)nm (4 weeks, t=2.971, P=0.002) and (54.65+/-12.52)nm (12 weeks, t=2.021, P=0.021). The rate of partial blink was relieved from 0.37+/ 0.30 (baseline) to 0.15+/-0.14 (4 weeks, t=3.428, P=0.035) and 0.12+/-0.13 (12 weeks, t=1.986, P=0.026). BUT was increased from (4.73+/- 2.34)s (baseline) to (9.32 +/- 2.18)s (4 weeks, t=3.385, P<0.001) and (9.91 +/- 3.01)s (12 weeks, t=3.253, P< 0.001). There were no unanticipated or serious device-related adverse events reported. Compared with baseline, there was no statistically significant difference in BCVA, corneal staining and intraocular pressure (P=0.141, 0.376, 0.421). CONCLUSION: The LipiFlow system was a safety and effectiveness treatment of MGD in the 12-week study. PMID- 26888278 TI - [Progresses of DNA methylation in common ocular tumor]. AB - DNA methylation is a major event of epigenetic modifications. In the presence of DNA methyltransferases (DNMT), the addition of methyl groups from cytosines can impact gene expression and alter cell and organism function. Methyl groups of CpG sites in the promoter can directly interfere with binding of transcription factors to their recognition cis elements or, on the other side, can facilitate interaction with a family of methyl-binding proteins and result in gene silencing. Analysis of DNA methylation includes genome-wide DNA methylation assessment, analysis of gene-specific DNA methylation and finding of new DNA methylation sites. The implication of DNA methylation has been suggested with the pathogenesis of retinoblastoma, uveal tract melanoma and ocular surface tumor. We focus on the progresses of DNA methylation on ocular tumors in this article. PMID- 26888279 TI - Atomic-scale simulation to study the dynamical properties and local structure of Cu-Zr and Ni-Zr metallic glass-forming alloys. AB - Molecular dynamics simulation with well-developed EAM potentials was carried out to investigate the transport properties and local atomic structure of Cu-Zr and Ni-Zr metallic glasses and supercooled liquids. It is found that Cu or Ni atoms have much faster dynamics than Zr atoms in relaxation timescales, while Zr atoms display faster dynamics in the Cu-Zr system than in the Ni-Zr system. A dynamical crossover phenomenon from Arrhenius to super-Arrhenius behavior in the transport properties was observed for the Cu65Zr35 system at Tx ~ 1250 K and the Ni65Zr35 system at Tx ~ 1500 K, respectively. Further structural analysis suggests that the dominant interconnected clusters in Cu65Zr35 and Ni65Zr35 systems are <0, 0, 12, 0>, <0, 1, 10, 2>, <0, 2, 8, 2> and <0, 3, 6, 4>. To directly characterize and visualize the correlated dynamics, we regard the full icosahedra as the microscopic origin responsible for the formation of metallic glasses in the Cu65Zr35 system, while the metallic glass formation in the Ni65Zr35 system can be attributed to the slow dynamics of <0, 3, 6, 4>, <0, 2, 8, 2> and <0, 1, 10, 2> Ni-centered Voronoi polyhedra. The local atomic order and dynamics for Cu65Zr35 and Ni65Zr35 systems are remarkably different, and these differences are presumed to hinder crystal nucleation and growth, hence promoting the largely different bulk glass-forming ability. PMID- 26888280 TI - Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China)). AB - Recent studies have suggested an association between vitamin D and non-alcoholic fatty liver disease (NAFLD); however, some results are subject to debate. This study was carried out to evaluate the correlation between NAFLD and vitamin D in men and women in East China. The data were obtained from a cross-sectional study that focused on the health and metabolic status of adults in sixteen areas of East China. According to ultrasonic assessments, the patients were divided into normal and NAFLD groups. Demographic characteristics and biochemical measurements were obtained. Binary logistic regression analysis was used to explore the association. In total, 5066 subjects were enrolled, and 2193 (43.3 %) were diagnosed with NAFLD; 84.56 % of the subjects showed vitamin D deficiency. Subjects with high vitamin D levels had a lower prevalence of NAFLD, particularly male subjects. Within the highest quartile of vitamin D levels, the prevalence of NAFLD was 40.8 %, whereas the lowest quartile of vitamin D levels showed a prevalence of 62.2 %, which was unchanged in women across the vitamin D levels. Binary logistic analysis showed that decreased vitamin D levels were associated with an increased risk of NAFLD (OR 1.54; 95 % CI 1.26, 1.88). This study suggests that vitamin D levels are significantly associated with NAFLD and that vitamin D acts as an independent factor for NAFLD prevalence, particularly in males in East China. Vitamin D interventional treatment might be a new target for controlling NAFLD; elucidating the mechanism requires further research. PMID- 26888281 TI - Erratum to: Severe Mycobacterial Diseases in a Patient with GOF IkappaBalpha Mutation Without EDA. PMID- 26888282 TI - In vitro metabolism of the synthetic cannabinoid 3,5-AB-CHMFUPPYCA and its 5,3 regioisomer and investigation of their thermal stability. AB - Recently, the pyrazole-containing synthetic cannabinoid N-(1-amino-3-methyl-1 oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) has been identified as a 'research chemical' both in powdered form and as an adulterant present in herbal preparations. Urine is the most common matrix used for abstinence control and the extensive metabolism of synthetic cannabinoids requires implementation of targeted analysis. The present study describes the investigation of the in vitro phase I metabolism of 3,5-AB CHMFUPPYCA and its regioisomer 5,3-AB-CHMFUPPYCA using pooled human liver microsomes. Metabolic patterns of both AB-CHMFUPPYCA isomers were qualitatively similar and dominated by oxidation of the cyclohexylmethyl side chain. Biotransformation to monohydroxylated metabolites of high abundance confirmed that these species might serve as suitable targets for urine analysis. Furthermore, since synthetic cannabinoids are commonly administered by smoking and because some metabolites can also be formed as thermolytic artefacts, the stability of both isomers was assessed under smoking conditions. Under these conditions, pyrolytic cleavage of the amide bond occurred that led to approximately 3 % conversion to heat-induced degradation products that were also detected during metabolism. These artefactual 'metabolites' could potentially bias in vivo metabolic profiles after smoking and might have to be considered for interpretation of metabolite findings during hair analysis. This might be relevant to the analysis of hair samples where detection of metabolites is generally accepted as a strong indication of drug use rather than a potential external contamination. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888283 TI - 70S-scanning initiation is a novel and frequent initiation mode of ribosomal translation in bacteria. AB - According to the standard model of bacterial translation initiation, the small ribosomal 30S subunit binds to the initiation site of an mRNA with the help of three initiation factors (IF1-IF3). Here, we describe a novel type of initiation termed "70S-scanning initiation," where the 70S ribosome does not necessarily dissociate after translation of a cistron, but rather scans to the initiation site of the downstream cistron. We detailed the mechanism of 70S-scanning initiation by designing unique monocistronic and polycistronic mRNAs harboring translation reporters, and by reconstituting systems to characterize each distinct mode of initiation. Results show that 70S scanning is triggered by fMet tRNA and does not require energy; the Shine-Dalgarno sequence is an essential recognition element of the initiation site. IF1 and IF3 requirements for the various initiation modes were assessed by the formation of productive initiation complexes leading to synthesis of active proteins. IF3 is essential and IF1 is highly stimulating for the 70S-scanning mode. The task of IF1 appears to be the prevention of untimely interference by ternary aminoacyl (aa)-tRNA*elongation factor thermo unstable (EF-Tu)*GTP complexes. Evidence indicates that at least 50% of bacterial initiation events use the 70S-scanning mode, underscoring the relative importance of this translation initiation mechanism. PMID- 26888284 TI - ROTUNDA3 function in plant development by phosphatase 2A-mediated regulation of auxin transporter recycling. AB - The shaping of organs in plants depends on the intercellular flow of the phytohormone auxin, of which the directional signaling is determined by the polar subcellular localization of PIN-FORMED (PIN) auxin transport proteins. Phosphorylation dynamics of PIN proteins are affected by the protein phosphatase 2A (PP2A) and the PINOID kinase, which act antagonistically to mediate their apical-basal polar delivery. Here, we identified the ROTUNDA3 (RON3) protein as a regulator of the PP2A phosphatase activity in Arabidopsis thaliana. The RON3 gene was map-based cloned starting from the ron3-1 leaf mutant and found to be a unique, plant-specific gene coding for a protein with high and dispersed proline content. The ron3-1 and ron3-2 mutant phenotypes [i.e., reduced apical dominance, primary root length, lateral root emergence, and growth; increased ectopic stages II, IV, and V lateral root primordia; decreased auxin maxima in indole-3-acetic acid (IAA)-treated root apical meristems; hypergravitropic root growth and response; increased IAA levels in shoot apices; and reduced auxin accumulation in root meristems] support a role for RON3 in auxin biology. The affinity-purified PP2A complex with RON3 as bait suggested that RON3 might act in PIN transporter trafficking. Indeed, pharmacological interference with vesicle trafficking processes revealed that single ron3-2 and double ron3-2 rcn1 mutants have altered PIN polarity and endocytosis in specific cells. Our data indicate that RON3 contributes to auxin-mediated development by playing a role in PIN recycling and polarity establishment through regulation of the PP2A complex activity. PMID- 26888285 TI - Targeted axonal import (TAxI) peptide delivers functional proteins into spinal cord motor neurons after peripheral administration. AB - A significant unmet need in treating neurodegenerative disease is effective methods for delivery of biologic drugs, such as peptides, proteins, or nucleic acids into the central nervous system (CNS). To date, there are no operative technologies for the delivery of macromolecular drugs to the CNS via peripheral administration routes. Using an in vivo phage-display screen, we identify a peptide, targeted axonal import (TAxI), that enriched recombinant bacteriophage accumulation and delivered protein cargo into spinal cord motor neurons after intramuscular injection. In animals with transected peripheral nerve roots, TAxI delivery into motor neurons after peripheral administration was inhibited, suggesting a retrograde axonal transport mechanism for delivery into the CNS. Notably, TAxI-Cre recombinase fusion proteins induced selective recombination and tdTomato-reporter expression in motor neurons after intramuscular injections. Furthermore, TAxI peptide was shown to label motor neurons in the human tissue. The demonstration of a nonviral-mediated delivery of functional proteins into the spinal cord establishes the clinical potential of this technology for minimally invasive administration of CNS-targeted therapeutics. PMID- 26888286 TI - Expression of factor H binding protein in meningococcal strains can vary at least 15-fold and is genetically determined. AB - Factor H binding protein (fHbp) is a lipoprotein of Neisseria meningitidis important for the survival of the bacterium in human blood and a component of two recently licensed vaccines against serogroup B meningococcus (MenB). Based on 866 different amino acid sequences this protein is divided into three variants or two families. Quantification of the protein is done by immunoassays such as ELISA or FACS that are susceptible to the sequence variation and expression level of the protein. Here, selected reaction monitoring mass spectrometry was used for the absolute quantification of fHbp in a large panel of strains representative of the population diversity of MenB. The analysis revealed that the level of fHbp expression can vary at least 15-fold and that variant 1 strains express significantly more protein than variant 2 or variant 3 strains. The susceptibility to complement-mediated killing correlated with the amount of protein expressed by the different meningococcal strains and this could be predicted from the nucleotide sequence of the promoter region. Finally, the absolute quantification allowed the calculation of the number of fHbp molecules per cell and to propose a mechanistic model of the engagement of C1q, the recognition component of the complement cascade. PMID- 26888288 TI - Intraguild predation influences oviposition behavior of blow flies (Diptera: Calliphoridae). AB - The objective of the present study was to determine whether blow flies (Diptera: Calliphoridae) are able to identify larvae of an intraguild predator species in the substrate and avoid laying eggs there. Blow flies oviposited in traps with different treatments: substrate only and substrate with larvae of Chrysomya albiceps (Wiedemann, 1819), Chrysomya megacephala (Fabricius, 1794), or Chrysomya putoria (Wiedemann, 1830). Ch. megacephala, Ch. putoria, and Lucilia eximia (Wiedemann, 1819) avoided laying eggs in the trap containing Ch. albiceps larvae. Cochliomyia macellaria (Fabricius, 1775) did not oviposit differently in each substrate but had overall low abundance. The prevalence of species on corpses may be influenced by the ability of the species to detect the presence of other species, mainly predators. In this sense, intraguild predation may result in misinterpretations of a crime scene and should be considered when assessing the minimum postmortem interval. PMID- 26888287 TI - Characterization and small-molecule stabilization of the multisite tandem binding between 14-3-3 and the R domain of CFTR. AB - Cystic fibrosis is a fatal genetic disease, most frequently caused by the retention of the CFTR (cystic fibrosis transmembrane conductance regulator) mutant protein in the endoplasmic reticulum (ER). The binding of the 14-3-3 protein to the CFTR regulatory (R) domain has been found to enhance CFTR trafficking to the plasma membrane. To define the mechanism of action of this protein-protein interaction, we have examined the interaction in vitro. The disordered multiphosphorylated R domain contains nine different 14-3-3 binding motifs. Furthermore, the 14-3-3 protein forms a dimer containing two amphipathic grooves that can potentially bind these phosphorylated motifs. This results in a number of possible binding mechanisms between these two proteins. Using multiple biochemical assays and crystal structures, we show that the interaction between them is governed by two binding sites: The key binding site of CFTR (pS768) occupies one groove of the 14-3-3 dimer, and a weaker, secondary binding site occupies the other binding groove. We show that fusicoccin-A, a natural-product tool compound used in studies of 14-3-3 biology, can stabilize the interaction between 14-3-3 and CFTR by selectively interacting with a secondary binding motif of CFTR (pS753). The stabilization of this interaction stimulates the trafficking of mutant CFTR to the plasma membrane. This definition of the druggability of the 14-3-3-CFTR interface might offer an approach for cystic fibrosis therapeutics. PMID- 26888290 TI - Letter to the Editor: Should we focus on quality or quantity in meta-analyses? PMID- 26888289 TI - A new type of quinoxalinone derivatives affects viability, invasion, and intracellular growth of Toxoplasma gondii tachyzoites in vitro. AB - Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2 ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 MUM +/- 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis. PMID- 26888291 TI - Genetic association between NRG1 and schizophrenia, major depressive disorder, bipolar disorder in Han Chinese population. AB - Schizophrenia, major depressive disorder, and bipolar disorder are three major psychiatric disorders affecting around 0.66%, 3.3%, and 1.5% of the Han Chinese population respectively. Several genetic linkage analyses and genome wide association studies identified NRG1 as a susceptibility gene of schizophrenia, which was validated by its role in neurodevelopment, glutamate, and other neurotransmitter receptor expression regulation. To further investigate whether NRG1 is a shared risk gene for major depressive disorder, bipolar disorder as well as schizophrenia, we performed an association study among 1,248 schizophrenia cases, 1,056 major depression cases, 1,344 bipolar disorder cases, and 1,248 controls. Totally 15 tag SNPs were genotyped and analyzed, and no population stratification was found in our sample set. Among the sites, rs4236710 (corrected Pgenotye = 0.015) and rs4512342 (Pallele = 0.03, Pgenotye = 0.045 after correction) were associated with schizophrenia, and rs2919375 (corrected Pgenotye = 0.004) was associated with major depressive disorder. The haplotype rs4512342-rs6982890 showed association with schizophrenia (P = 0.03 for haplotype "TC" after correction), and haplotype rs4531002-rs11989919 proved to be a shared risk factor for both major depressive disorder ("CC": corrected P = 0.009) and bipolar disorder ("CT": corrected P = 0.003). Our results confirmed that NRG1 was a shared common susceptibility gene for major mental disorders in Han Chinese population. PMID- 26888292 TI - Cigarette smoking lowers blood pressure in adolescents: the Irbid-TRY. AB - OBJECTIVE: Tobacco consumption adversely affects cardiovascular (CV) disease (CVD) and risk profile, including hypertension. The long-term effect of cigarette smoking on blood pressure (BP) in adolescents is still, however, equivocal. Thus, the current study examined the CV indices in male adolescent cigarette smokers versus nonsmokers. METHOD: Resting heart rate, systolic BP (SBP) and diastolic BP (DBP), mean arterial pressure (MAP), pulse pressure (PP) and rate pressure products (RPP) were examined using automatic oscillatory method, while smoking status was determined with Youth Risk Behavior Survey. RESULTS: After controlling for cofactors, the ANCOVA showed that CV measures in the male adolescent smokers were lower (p < 0.05) than nonsmokers. Additionally, regression showed that smoking status explained 20.6% of SBP, 5.0% of DBP, 13.4% of MAP, 7.5% of PP and 13.4% of RPP. CONCLUSION: The results suggest that cigarette smoking lowers CV measures in adolescents. However, more studies are needed to describe the mechanism(s) for lowering CV measures and explain the relationship of adolescent smoking with adulthood CVDs. PMID- 26888293 TI - Comparative genomics of mitochondria in chlorarachniophyte algae: endosymbiotic gene transfer and organellar genome dynamics. AB - Chlorarachniophyte algae possess four DNA-containing compartments per cell, the nucleus, mitochondrion, plastid and nucleomorph, the latter being a relic nucleus derived from a secondary endosymbiont. While the evolutionary dynamics of plastid and nucleomorph genomes have been investigated, a comparative investigation of mitochondrial genomes (mtDNAs) has not been carried out. We have sequenced the complete mtDNA of Lotharella oceanica and compared it to that of another chlorarachniophyte, Bigelowiella natans. The linear mtDNA of L. oceanica is 36.7 kbp in size and contains 35 protein genes, three rRNAs and 24 tRNAs. The codons GUG and UUG appear to be capable of acting as initiation codons in the chlorarachniophyte mtDNAs, in addition to AUG. Rpl16, rps4 and atp8 genes are missing in L.oceanica mtDNA, despite being present in B. natans mtDNA. We searched for, and found, mitochondrial rpl16 and rps4 genes with spliceosomal introns in the L. oceanica nuclear genome, indicating that mitochondrion-to-host nucleus gene transfer occurred after the divergence of these two genera. Despite being of similar size and coding capacity, the level of synteny between L. oceanica and B. natans mtDNA is low, suggesting frequent rearrangements. Overall, our results suggest that chlorarachniophyte mtDNAs are more evolutionarily dynamic than their plastid counterparts. PMID- 26888294 TI - Migraine biomarkers in cerebrospinal fluid: A systematic review and meta analysis. AB - Objective To perform a meta-analysis of migraine biomarkers in cerebrospinal fluid (CSF) and of corresponding blood concentrations. Methods We conducted a systematic search for studies that measured biochemical compounds in CSF of chronic or episodic migraineurs and non-headache controls. Subsequent searches retrieved studies with blood measurements of selected CSF biomarkers. If a compound was assessed in three or more studies, results were pooled in a meta analysis with standardised mean differences (SMD) as effect measures. Results Sixty-two compounds were measured in 40 CSF studies. Most important results include: increased glutamate (five studies, SMD 2.22, 95% CI: 1.30, 3.13), calcitonin gene-related peptide (CGRP) (three studies, SMD: 3.80, 95% CI: 3.19, 4.41) and nerve growth factor (NGF) (three studies, SMD: 6.47, 95% CI: 5.55, 7.39) in chronic migraine patients and decreased beta-endorphin (beta-EP) in both chronic (four studies, SMD: -1.37, 95% CI: -1.80, -0.94) and interictal episodic migraine patients (three studies, SMD: -1.12, 95% CI: -1.65, -0.58). In blood, glutamate (interictal) and CGRP (chronic, interictal and ictal) were increased and beta-EP (chronic, interictal and ictal) was decreased. Conclusions Glutamate, beta-EP, CGRP and NGF concentrations are altered in CSF and, except for NGF, also in blood of migraineurs. Future research should focus on the pathophysiological roles of these compounds in migraine. PMID- 26888297 TI - Big Data Transforms Discovery-Utilization Therapeutics Continuum. AB - Enabling omic technologies adopt a holistic view to produce unprecedented insights into the molecular underpinnings of health and disease, in part, by generating massive high-dimensional biological data. Leveraging these systems level insights as an engine driving the healthcare evolution is maximized through integration with medical, demographic, and environmental datasets from individuals to populations. Big data analytics has accordingly emerged to add value to the technical aspects of storage, transfer, and analysis required for merging vast arrays of omic-, clinical-, and eco-datasets. In turn, this new field at the interface of biology, medicine, and information science is systematically transforming modern therapeutics across discovery, development, regulation, and utilization. PMID- 26888300 TI - Late anastomotic leakage after low anterior resection in rectal cancer patients: clinical characteristics and predisposing factors. AB - AIM: The purpose was to examine the clinical characteristics and predisposing factors of late anastomotic leakage following low anterior resection for rectal cancer. METHOD: We retrospectively evaluated the clinicopathological features of patients who experienced anastomotic leakage after low anterior resection for rectal cancer. Patients were divided into two groups according to the time to leakage: early leakage (within 30 days postoperatively) and late leakage (after 30 days postoperatively). Clinicopathological characteristics were compared between the two groups. RESULTS: Anastomotic leakage occurred in 141 patients. Anastomotic leakage was diagnosed at a median of 17 (range 0-886) days postoperatively; 85 (60.3%) and 56 (39.7%) were categorized as the early and late leakage groups, respectively. Radiotherapy (hazard ratio 5.007; 95% CI 2.208 11.354; P < 0.0001) was the only significant independent predisposing factor for late leakage. Diverting stoma did not protect against late leakage. The late leakage group more frequently had the fistula type (46.4% vs. 10.6%; P < 0.001) and less frequently needed laparotomy (55.4% vs. 78.8%; P = 0.001). The rate of long-term stoma over 1 year was greater in the late leakage than the early leakage group (51.8% vs. 29.4%; P = 0.009). CONCLUSION: Late anastomotic leakages that develop after 30 days following low anterior resection are not uncommon and may be associated with the use of radiotherapy. Late leakage should be a different entity from early leakage in terms of the type of leakage, methods of management and subsequent sequelae. PMID- 26888302 TI - The Interdisciplinarity of Collaborations in Cognitive Science. AB - We introduce a new metric for interdisciplinarity, based on co-author publication history. A published article that has co-authors with quite different publication histories can be deemed relatively "interdisciplinary," in that the article reflects a convergence of previous research in distinct sets of publication outlets. In recent work, we have shown that this interdisciplinarity metric can predict citations. Here, we show that the journal Cognitive Science tends to contain collaborations that are relatively high on this interdisciplinarity metric, at about the 80th percentile of all journals across both social and natural sciences. Following on Goldstone and Leydesdorff (2006), we describe how scientometric tools provide a valuable means of assessing the role of cognitive science in broader scientific work, and also as a tool to investigate teamwork and distributed cognition. We describe how data-driven metrics of this kind may facilitate this exploration without relying upon rapidly changing discipline and topic keywords associated with publications. PMID- 26888301 TI - Development and Pharmacological Characterization of Selective Blockers of 2 Arachidonoyl Glycerol Degradation with Efficacy in Rodent Models of Multiple Sclerosis and Pain. AB - We report the discovery of compound 4a, a potent beta-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood-brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity. Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol and behaves as a cannabinoid (CB1/CB2) receptor indirect agonist. Administration of 4a in mice suffering from experimental autoimmune encephalitis ameliorates the severity of the clinical symptoms in a CB1/CB2-dependent manner. Moreover, 4a produced analgesic effects in a rodent model of acute inflammatory pain, which was antagonized by CB1 and CB2 receptor antagonists/inverse agonists. 4a also relieves the neuropathic hypersensitivity induced by oxaliplatin. Given these evidence, 4a, as MGL selective inhibitor, could represent a valuable lead for the future development of therapeutic options for multiple sclerosis and chronic pain. PMID- 26888295 TI - Accelerating chemical exchange saturation transfer (CEST) MRI by combining compressed sensing and sensitivity encoding techniques. AB - PURPOSE: To evaluate the feasibility of accelerated chemical-exchange-saturation transfer (CEST) imaging using a combination of compressed sensing (CS) and sensitivity encoding (SENSE) at 3 Tesla. THEORY AND METHODS: Two healthy volunteers and six high-grade glioma patients were recruited. Raw CEST image k space data were acquired (with varied radiofrequency saturation power levels for the healthy volunteer study), and a sequential CS and SENSE reconstruction (CS SENSE) was assessed. The MTRasym (3.5 ppm) signals were compared with varied CS SENSE acceleration factors. RESULTS: In the healthy volunteer study, a CS-SENSE acceleration factor of R = 2 * 2 (CS * SENSE) was achieved without compromising the reconstructed MTRasym (3.5 ppm) image quality. The MTRasym (3.5 ppm) signals obtained from the CS-SENSE reconstruction with R = 2 * 2 were well preserved compared with the reference image (R = 2 for only SENSE). In the glioma patient study, the MTRasym (3.5 ppm) signals were significantly higher in the tumor region (Gd-enhancing tumor core) than in the normal-appearing white matter (P < 0.001). There was no significant MTRasym (3.5 ppm) difference between the reference image and CS-SENSE-reconstructed image in the acceleration factor of R = 2 * 2. CONCLUSION: Combining the SENSE technique with CS (R = 2 * 2) enables considerable acceleration of CEST image acquisition and potentially has a wide range of clinical applications. Magn Reson Med 77:779-786, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26888303 TI - n-butylparaben induces male reproductive disorders via regulation of estradiol and estrogen receptors. AB - It is well known that inappropriate exposure to exogenous hormones during fetal or neonatal life, such as testosterone (T) and estradiol (E2 ), leads to adverse reproductive outcomes. In our previous study, the reproductive dysfunction of male rats was characterized by an E2 increase and T decrease after in utero and lactation exposures to n-butylparaben (n-BP). In this study, we investigated the synthesis and metabolism pathways of steroid hormones, hormone receptors and the epigenetic modification of male offspring on postnatal day (PND) 21 and PND90 to explore the possible mechanisms of endocrine and reproductive disorders. The expression of steroidogenic acute regulatory protein (StAR), cytochrome cholesterol side-chain cleavage enzyme (P450scc), estrogen sulfotransferase (SULT1E1) and androgen receptor (AR) in the testes was significantly decreased at the transcript and protein levels; in addition, aromatase (CYP19) and estrogen receptor alpha (ERalpha) expression was significantly increased and the methylation rate of the ERalpha promoter was significantly decreased. These results suggest that increased CYP19 expression and decreased SULT1E1 expression are responsible for the E2 increase. This effect promotes the expression of ERalpha, which plays a pivotal role in regulating reproductive and endocrine disorders of male rats exposed to n-BP. Furthermore, the epigenetic hypomethylation of ERalpha is involved in this regulation processes. Our study is the first to report on the possible mechanism of male rat reproductive disorders induced by the xenoestrogenic chemical n-BP. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888305 TI - The Choroid Plexus in Healthy and Diseased Brain. AB - The choroid plexus is composed of epithelial cells resting on a basal lamina. These cells produce the cerebrospinal fluid (CSF), which has many functions including rendering mechanical support, providing a route for some nutrients, removing by-products of metabolism and synaptic activity, and playing a role in hormonal signaling. The choroid plexus synthesizes many growth factors, including insulin-like, fibroblast, and platelet-derived growth factors. The tight junctions located between the apical parts of the choroid plexus epithelial cells form the blood-CSF barrier (BCSFB), which is crucial for the homeostatic regulation of the brain microenvironment along with the blood-brain barrier (BBB). Morphological changes such as atrophy of the epithelial cells and thickening of the basement membrane suggest altered CSF production occurs in aging and in Alzheimer disease. In brain injuries and infections, leukocytes accumulate in the CSF by passing through the choroid plexus. In inflammatory CNS diseases (eg, multiple sclerosis), pathogenic autoreactive T lymphocytes may migrate through the BBB and BCSFB into the CNS. The development of therapeutic strategies to mitigate disruption of the BCSFB may be helpful to curtail the entry of inflammatory cells into the CSF and hence reduce inflammation, thereby overcoming choroid plexus dysfunction in senescence and in various diseases of the CNS. PMID- 26888306 TI - Inflammatory Cytokines Are Involved in Focal Demyelination in Leprosy Neuritis. AB - Mycobacterium leprae (ML) infection causes nerve damage that often leads to permanent loss of cutaneous sensitivity and limb deformities, but understanding of the pathogenesis of leprous neuropathy that would lead to more effective treatments is incomplete. We studied reactional leprosy patients with (n = 9) and without (n = 8) acute neuritis. Nerve conduction studies over the course of the reactional episode showed the findings of demyelination in all patients with neuritis. Evaluation of patient sera revealed no correlation of the presence of antibodies against gangliosides and the clinical demyelination. In nerve biopsies of 3 patients with neuritis, we identified tumor necrosis factor (TNF), TNF receptors, and TNF-converting enzyme in Schwann cells (SCs) using immunofluorescence. To elucidate immunopathogenetic mechanisms, we performed experiments using a human SC line. ML induced transmembrane TNF and TNF receptor 1 expression in the SCs; TNF also induced interleukin (IL)- 6 and IL-8 production by the SCs; and ML induced IL-23 secretion, indicating involvement of this previously unrecognized factor in leprosy nerve damage. These data suggest that ML may contribute to TNF-mediated inflammation and focal demyelination by rendering SCs more sensitive to TNF within the nerves of patients with leprous neuropathy. PMID- 26888307 TI - Water-soluble poly(2,7-dibenzosilole) as an ultra-bright fluorescent label for antibody-based flow cytometry. AB - A series of novel water-soluble PEGylated dibenzosilole-based conjugated polymers were prepared as ultra-bright fluorescent labels for biomolecules. Due to their superior solubility and brightness, antibody conjugates labeled with functionalized polymers showed significantly enhanced signal and sensitivity relative to traditional fluorophores in functional flow cytometry applications. PMID- 26888304 TI - Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database. AB - Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal beta-amyloid protein precursor processing. PMID- 26888308 TI - Psychiatric disorders: Linking genetic risk to pruning. PMID- 26888310 TI - Systemic therapies in the treatment of non-small-cell lung cancer brain metastases. AB - Non-small-cell lung cancer (NSCLC) brain metastases are common. Even though there are various subsets of NSCLC with molecular alterations, there is a common theme of brain metastases. Current treatment modalities are suboptimal. Systemic therapies for the treatment of NSCLC brain metastases have been explored and recent advances may pave the way for their successful employment in this patient population. While no specific agents have been associated with a marked benefit, stability of disease as well as radiographic responses have been noted in some patients. Biological activity of systemic therapies in some patients with NSCLC brain metastases raises hope for future advances and supports further investigation for this patient population with limited treatment options. PMID- 26888311 TI - Thermodynamics of deposition flux-dependent intrinsic film stress. AB - Vapour deposition on polycrystalline films can lead to extremely high levels of compressive stress, exceeding even the yield strength of the films. A significant part of this stress has a reversible nature: it disappears when the deposition is stopped and re-emerges on resumption. Although the debate on the underlying mechanism still continues, insertion of atoms into grain boundaries seems to be the most likely one. However, the required driving force has not been identified. To address the problem we analyse, here, the entire film system using thermodynamic arguments. We find that the observed, tremendous stress levels can be explained by the flux-induced entropic effects in the extremely dilute adatom gas on the surface. Our analysis justifies any adatom incorporation model, as it delivers the underlying thermodynamic driving force. Counterintuitively, we also show that the stress levels decrease, if the barrier(s) for adatoms to reach the grain boundaries are decreased. PMID- 26888309 TI - Addressing the Requirements of High-Sensitivity Single-Molecule Imaging of Low Copy-Number Proteins in Bacteria. AB - Single-molecule fluorescence super-resolution imaging and tracking provide nanometer-scale information about subcellular protein positions and dynamics. These single-molecule imaging experiments can be very powerful, but they are best suited to high-copy number proteins where many measurements can be made sequentially in each cell. We describe artifacts associated with the challenge of imaging a protein expressed in only a few copies per cell. We image live Bacillus subtilis in a fluorescence microscope, and demonstrate that under standard single molecule imaging conditions, unlabeled B. subtilis cells display punctate red fluorescent spots indistinguishable from the few PAmCherry fluorescent protein single molecules under investigation. All Bacillus species investigated were strongly affected by this artifact, whereas we did not find a significant number of these background sources in two other species we investigated, Enterococcus faecalis and Escherichia coli. With single-molecule resolution, we characterize the number, spatial distribution, and intensities of these impurity spots. PMID- 26888312 TI - Feasibility and Effects of a Brief Compassion-Focused Imagery Intervention in Psychotic Patients with Paranoid Ideation: A Randomized Experimental Pilot Study. AB - : Paranoia is characterized by a lack of perceived social safeness and associated negative affect. Low self-esteem, negative self-concepts and negative emotions have been shown to contribute to paranoid symptom formation. Thus, interventions focusing on affiliation and positive affect might be particularly helpful for patients with paranoia. The present study experimentally tested the effect of a one-session, brief compassion-focused imagery derived from Compassion-Focused Therapy (Gilbert, ) versus a control imagery condition in a repeated measures randomized design. A negative affective state was induced via in-sensu exposure to a recent distressful social situation in order to provide a minimum level of threat-related arousal to be down-regulated by the interventions thereafter. The sample consisted of psychotic patients with paranoid ideation (N = 51) who were randomly assigned to one of the experimental conditions. Effects on postulated causal mechanisms, i.e., self-relating (self-reassurance, self-compassion, self criticism), and affect (self-reported affective states, skin conductance levels) as well as on state paranoia, were tested. Subjective benefit and appraisals of the intervention were explored. There were no specific intervention effects on negative self-relating, negative affect and skin-conductance or on paranoia. However, compassion-focused imagery had significant effects on self-reassurance and happiness. Explorative analyses revealed that the majority of the participants appraised the intervention in a positive manner, indicating good acceptance. The intervention showed an effect on some of the postulated mechanisms but not on others, which might have been because of its brevity. Further investigation of interventions targeting affiliation for people with paranoid experiences appears worthwhile. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Affiliative imagery work is feasible and appraised positively in psychotic patients. Brief compassion focused imagery increased feelings of happiness and reassurance but did not improve negative self-relating, negative affect or paranoia. Further investigation is warranted to identify which patients benefit most from affiliative imagery. PMID- 26888315 TI - Clinical relevance of antigen spreading pattern induced by CHP-MAGE-A4 cancer vaccination. AB - AIM: To investigate the antigen spreading pattern in the CHP-MAGE-A4-vaccinated patients and analyze the clinical relevance of antigen spreading pattern as a surrogate marker of patient survival. MATERIALS & METHODS: 12 patients who had been injected with 300 MUg of CHP-MAGE-A4 and 0.5 Klinische Einheit of OK-432 in more than five vaccinations were analyzed. RESULTS: Increases in the anti-MAGE-A4 specific antibody response were observed in eight patients (66.7%), compared with six patients (50%) for anti-NY-ESO-1 and five patients (41.7%) for anti-MAGE-A3 after five vaccinations. We identified frequent antigen spreading following MAGE A4 vaccinations without associations with the clinical response or patient prognosis. CONCLUSION: Antigen spreading pattern might reflect tumor shrinkage as a response to treatment and treatment history (clinical trial registration number: UMIN000001999). PMID- 26888316 TI - Patient-Centred Care: The Proving Ground for Continuity and Equity in Our Health System. PMID- 26888317 TI - The Patient Experience in Ontario 2020: What Is Possible? AB - Words are important. They signal an intention behind a thought. So when Ontario's Ministry of Health and Long-Term Care publishes an action plan (Ontario Ministry of Health and Long-Term Care, 2012) that declares itself to be "obsessively patient-centred," curiosity ensues and terms abound. Patient-centred care, patient engagement and patient experience - all seem to be in the mix in Ontario. This paper will propose a set of definitions for these commonly used terms, examine the progress being made in Ontario towards a more patient-centred healthcare system and suggest where we might aim to be by 2020. PMID- 26888313 TI - Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFkappaB and nitric oxide pathways. AB - Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-alpha-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-alpha, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFkappaB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis. PMID- 26888318 TI - Language that Works for Everyone. AB - Efforts to improve quality in healthcare require concerted action on the part of clinical and non-clinical staff and everyone who works with them. In complex healthcare systems, it is important to frame aspirations and goals in a language that works for everyone. The words that work for everyone to describe what good patient experience is like are: "warm," "welcoming," "listening," "kind" and "friendly." The Change Foundation vision for 2020 is important. Experience in the UK suggests that more emphasis should be placed on relationships and culture as important levers in engagement with patients and quality improvement as well as important barriers to overcome. High-level organizational changes and technical solutions make the process of change sound easier than seems likely, given the height of some of the barriers. Major changes in healthcare, especially where they entail changes in culture, take a long time, not least because of the ordinary problems of management and human relationships. The paper anticipates a longer journey to reach the destination of a truly patient-centred system and full engagement with patients and suggests identifying some staging posts that can be celebrated along the way. PMID- 26888314 TI - miR-182 Modulates Myocardial Hypertrophic Response Induced by Angiogenesis in Heart. AB - Myocardial hypertrophy is an adaptive response to hemodynamic demands. Although angiogenesis is critical to support the increase in heart mass with matching blood supply, it may also promote a hypertrophic response. Previously, we showed that cardiac angiogenesis induced by placental growth factor (PlGF), promotes myocardial hypertrophy through the paracrine action of endothelium-derived NO, which triggers the degradation of regulator of G protein signaling 4 (RGS4) to activate the Akt/mTORC1 pathways in cardiomyocytes. Here, we investigated whether miRNAs contribute to the development of hypertrophic response associated with myocardial angiogenesis. We show that miR-182 is upregulated concurrently with the development of hypertrophy in PlGF mice, but not when hypertrophy was blocked by concomitant expression of PlGF and RGS4, or by PlGF expression in eNOS(-/-) mice. Anti-miR-182 treatment inhibits the hypertrophic response and prevents the Akt/mTORC1 activation in PlGF mice and NO-treated cardiomyocytes. miR-182 reduces the expression of Bcat2, Foxo3 and Adcy6 to regulate the hypertrophic response in PlGF mice. Particularly, depletion of Bcat2, identified as a new miR-182 target, promotes Akt(Ser473)/p70-S6K(Thr389) phosphorylation and cardiomyocyte hypertrophy. LV pressure overload did not upregulate miR-182. Thus, miR-182 is a novel target of endothelial-cardiomyocyte crosstalk and plays an important role in the angiogenesis induced-hypertrophic response. PMID- 26888319 TI - Winning Conditions? AB - The authors of the paper, "The Patient Experience in Ontario 2020: What is Possible?", framed both the current state as well as the future of what patient experience might look like in five years. To ensure intention is catalyzed into meaningful change to improve experience and outcomes, we suggest four winning conditions. The first is to change the language; patients are people too, irrespective of their disease or illness; person-centred is inclusive language and ought to be the focus. The second condition is focused on leaders who play a critical role to establish, build and embed person-centred within the organization. The third and fourth winning conditions are building the evidence base and using effective and meaningful engagement, moving beyond advice, to partnership, respectively. Person-centred care is not the flavour of the month, it is here to stay. Ontarians are important actors in the system not only as users of the system but owners as well. To those who might argue that it is costly to do this work, what are the costs to not engage? Are we satisfied not only as administrators, and clinicians, but as patients at some point, to maintain the status quo? PMID- 26888320 TI - Finding Common Ground in Patient-Centred Care: Consensus, Communication and Conversations for Change. AB - Fooks et al. (2015) propose patient-centred care and engagement as "levers for change" in a healthcare system increasingly challenged to care for patients living with complex chronic illness. Patient-centred care, engagement and experience are presented as inherently relational concepts, but who is included under that relational umbrella is less clear. Using the rubric of "finding common ground" from the model of patient-centred care described by Hudon et al. (2011), I argue for including provider perspectives, not just patient/family. Otherwise the envisioned conversations of "change" will be missing the voices of those expected to facilitate the meaningful relational engagement of patients and the process of shared decision-making. I also discuss relational communication competence as a key factor in successful patient-engagement, patient-centred care and, ultimately, the healthcare experience. Without attention to both these elements - broadening the understanding of therapeutic relationship to encompass all contributing stakeholders and the relational communication competency so necessary to this endeavour - whatever consensus we reach will be missing important aspects related to actionable content and process, both of which are needed to guide the development of relevant metrics. Without metrics, we will lack rigorous "evidence" with which to make the case that patient-centred care and engagement are indeed "levers" for positive system reform. PMID- 26888321 TI - Patient Engagement: Time to Shake the Foundations. AB - Something big is happening in healthcare. It's not the new Apple Watch, 3D printing or the advent of personalized medicine. It's people power. And, it is starting to shake up the very foundation on which healthcare systems around the world have been built. Healthcare professionals and hospitals are iconic features on a healthcare landscape that has been purpose-built with castles, moats and defence artillery. Turf protection, often under the guise of "patient protection," has become so ingrained in the way things are that few recognize what it has become. Fooks et al. step gently into this somewhat dangerous territory for "insiders" of the system to tread; yet in my view, they do not go far enough. PMID- 26888322 TI - A Challenge to Aim Higher and Bolder. AB - The paper "The Patient Experience in Ontario 2020: What Is Possible?" provides useful context setting, definitions that frame the essential principles of good relationships and challenges for outcomes by 2020 for the people of Ontario. The question - Is it ambitious enough to achieve a patient-centred healthcare system by 2020? Does it build on the deep strengths already evident in Ontario to achieve the outcomes essential to a thriving region? Will the challenges accelerate dramatically improved outcomes in better health, better care and lower costs? The risk of aiming too low is that it allows for an incremental, comfortable-for-us-in-healthcare pace when what is required is ambitious, disruptive moves. This commentary offers suggestions for Winning Conditions that build on those proposed and takes steps beyond - Winning Conditions 2.0 - to assure a health system the citizens of Ontario expect and deserve. PMID- 26888323 TI - Patient-Centred Measurement in British Columbia: Statistics without the Tears Wiped Off. AB - At the heart of every data point in healthcare is a person. British Columbia's (BC) province-wide, coordinated survey program, established in 2002, gives people who use BC's healthcare services a voice in improving the quality of the care and services they receive. Survey data or statistics are presented without the tears wiped off by integrating quantitative results along with a "human" voice or story annotated directly into reports to illustrate the numerical feedback. In this way the data represent the true lived experiences of people who use our healthcare services and allow us to evaluate our progress towards providing truly patient centred care. After over a decade of measurement and reporting of patient experiences, BC will pioneer a new approach. People who receive healthcare services in BC will be asked to provide feedback across their entire episode of care. And, because routine measurement of patient experiences and patient outcomes in healthcare is a provincial strategic objective, patients will be asked to assess both their experiences of care (patient self-reported experiences) and their outcomes of care (patient self-reported outcomes). This change in measurement strategy builds on 13 years of continuous improvement in patient-centred data collection, reporting and action based on feedback from BC's patients and families. PMID- 26888324 TI - Partnerships with Patients and Family Caregivers. AB - This paper discusses six areas of hospital experience that can be improved: parking, hospital gowns, visiting hours, emergency room triage, hospital food, and care plans and discharge summaries. The areas were identified by a group of patients and family caregivers who reviewed large numbers of patient experiences and identified simple and easy to measure changes. Their recommended changes are called "Key Performance Targets." PMID- 26888325 TI - The Age of Head Transplants. PMID- 26888326 TI - Cost-effectiveness of a risk-based secondary screening programme of type 2 diabetes. AB - OBJECTIVE: The objective of this study was to develop a long-term economic model for type 2 diabetes to describe the entire spectrum of the disease over a wide range of healthcare programmes. The model evaluates a public health, risk-based screening programme in a country specific setting. METHODS: The lifespan of persons and important phases of the disease and related interventions are recorded in a Markov model, which first simulates the effect of screening, then replicates important complications of diabetes, follows the progression of individuals through physiological variables and finally calculates outcomes in monetary and naturalistic units. RESULTS: The introduction of the screening programme nearly doubled the proportion of diagnosed patients at the age of 50 and prolonged life expectancy. Three-yearly screening gained 0.0229 quality adjusted life years for an additional ?83 per person compared with no screening and resulted an incremental cost-effectiveness ratio of ?3630/quality adjusted life years. CONCLUSION: From the economic perspective introduction of the 3 yearly screening programme is justifiable and it provides a good value for money. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888327 TI - Framing preventive care messaging and cervical cancer screening in a health insured population in South Africa: Implications for population-based communication? AB - The impact of health message framing on cervical cancer screening uptake is poorly understood. In a prospective randomized control study with 748 females, aged 21-65 years with no Pap smear in the previous 3 years, they randomly received a loss-framed, gain-framed, or neutral health message (control) regarding cervical cancer screening by email. Screening rate in the control group was 9.58 percent (CI: 9.29%-9.87%), 5.71 percent (CI: 5.48%-6.98%) in the gain framed group, and 8.53 percent (CI: 8.24%-8.81%) in the loss-framed group. Statistically there was no difference between the three screening rates. Framing of health messages may not be a significant consideration when communicating through emails. PMID- 26888329 TI - Piling Up Pillar[5]arenes To Self-Assemble Nanotubes. AB - New liquid-crystalline pillar[5]arene derivatives have been prepared by grafting first-generation Percec-type poly(benzylether) dendrons onto the macrocyclic scaffold. The molecules adopt a disc-shaped structure perfectly suited for self organization into a columnar liquid-crystalline phase. In this way, the pillar[5]arene cores are piled up, thus forming a nanotubular wire encased within a shell of peripheral dendrons. The capability of pillar[5]arenes to form inclusion complexes has been also exploited. Specifically, detailed binding studies have been carried out in solution with 1,6-dicyanohexane as the guest. Inclusion complexes have also been prepared in the solid state. Supramolecular organization into the Colh mesophase has been deduced from X-ray diffraction data and found to be similar to that observed within the crystal lattice of a model inclusion complex prepared from 1,4-dimethoxypillar[5]arene and 1,6 dicyanohexane. PMID- 26888331 TI - Space and time-resolved probing of heterogeneous catalysis reactions using lab-on a-chip. AB - Probing catalytic reactions on a catalyst surface in real time is a major challenge. Herein, we demonstrate the utility of a continuous flow millifluidic chip reactor coated with a nanostructured gold catalyst as an effective platform for in situ investigation of the kinetics of catalytic reactions by taking 5 (hydroxymethyl)furfural (HMF) to 2,5-furandicarboxylic acid (FDCA) conversion as a model reaction. The idea conceptualized in this paper can not only dramatically change the ability to probe the time-resolved kinetics of heterogeneous catalysis reactions but also used for investigating other chemical and biological catalytic processes, thereby making this a broad platform for probing reactions as they occur within continuous flow reactors. PMID- 26888328 TI - MU Opioid receptor: novel antagonists and structural modeling. AB - The MU opioid receptor (MOR) is a prominent member of the G protein-coupled receptor family and the molecular target of morphine and other opioid drugs. Despite the long tradition of MOR-targeting drugs, still little is known about the ligand-receptor interactions and structure-function relationships underlying the distinct biological effects upon receptor activation or inhibition. With the resolved crystal structure of the beta-funaltrexamine-MOR complex, we aimed at the discovery of novel agonists and antagonists using virtual screening tools, i.e. docking, pharmacophore- and shape-based modeling. We suggest important molecular interactions, which active molecules share and distinguish agonists and antagonists. These results allowed for the generation of theoretically validated in silico workflows that were employed for prospective virtual screening. Out of 18 virtual hits evaluated in in vitro pharmacological assays, three displayed antagonist activity and the most active compound significantly inhibited morphine induced antinociception. The new identified chemotypes hold promise for further development into neurochemical tools for studying the MOR or as potential therapeutic lead candidates. PMID- 26888330 TI - Oral immunotherapy for peanut allergy induces eosinophilic esophagitis: three pediatric case reports. PMID- 26888333 TI - Event-related brain potential and postural muscle activity during standing on an oscillating table while the knee, hip, and trunk are fixed. AB - BACKGROUND: In this study, a cast brace was used to immobilize the knee, hip, and trunk, and relations between the event-related brain potential (ERP) and postural muscle activity were investigated while standing on an oscillating table. METHODS: Twelve healthy young adults maintained a standing posture for 1 min per trial while oscillating in the anteroposterior direction at 0.5 Hz with a 2.5-cm amplitude. Trials were performed without and with the cast brace (no-fixation and fixation condition, respectively) until the subject had adapted to the floor oscillation. The ERP from the Cz electrode, postural muscle activity, and joint movement range were analyzed for the first and last two trials (before and after adaptation, respectively). RESULTS: Movement range of the hip and knee was lower in the fixation condition than in the no-fixation condition, and postural control was achieved by pivoting at the ankle. Peak muscle activity was largest in the gastrocnemius (GcM) in both conditions. GcM activity significantly increased after fixation and then decreased with adaptation. The time of peak erector spinae (ES) activity in the fixation condition was significantly earlier than in the no-fixation condition and was not significantly different from the time of the anterior reversal and peak of triceps surae activity. The negative ERP peaked approximately 80 ms after the anterior reversal. Significant correlations between the time of the peak negative ERP and the peak GcM, soleus, and ES activity were observed only after the adaptation, and were greater in the fixation condition (r = 0.83, 0.84, and 0.83, respectively) than in the no-fixation condition (r = 0.62, 0.73, and 0.51, respectively). CONCLUSION: All joints of the leg and trunk except for the ankle were rigidly fixed by the cast brace, and the phase differences between body segments were very small in the fixation condition. High correlations between the time of the peak negative ERP and the peak GcM, soleus, and ES activity after adaptation in the fixation condition suggest that attention would be more focused on anticipatory processing of muscle sensory information from the triceps surae and/or ES, particularly GcM, which had the greatest activation. PMID- 26888336 TI - Hydrogen production in microbial reverse-electrodialysis electrolysis cells using a substrate without buffer solution. AB - The aim of this work was to use substrate without buffer solution in a microbial reverse-electrodialysis electrolysis cell (MREC) for hydrogen production under continuous flow condition (10 cell pairs of RED stacks, HRT=5, 7.5, and 15h). Decreasing in the HRT (increasing in the organic matter) made cell current stable and increased. Hydrogen gas was produced at a rate of 0.61m(3)-H2/m(3)-Van/d in H MREC, with a COD removal efficiency of 81% (1.55g/L/d) and a Coulombic efficiency of 41%. This MREC system without buffer solution could successfully produce hydrogen gas at a consistent rate. PMID- 26888335 TI - Scaled-up dual anode/cathode microbial fuel cell stack for actual ethanolamine wastewater treatment. AB - The aim of this work was to develop the scale-up microbial fuel cell technology for actual ethanolamine wastewater treatment, dual anode/cathode MFC stacks connected in series to achieve any desired current, treatment capacity, and volume capacity. However, after feeding actual wastewater into the MFC, maximum power density decreased while the corresponding internal resistance increased. With continuous electricity production, a stack of eight MFCs in series achieved 96.05% of COD removal and 97.30% of ammonia removal at a flow rate of 15.98L/d (HRT 12h). The scaled-up dual anode/cathode MFC stack system in this research was demonstrated to treat actual ETA wastewater with the added benefit of harvesting electricity energy. PMID- 26888332 TI - Effects of silver nanoparticles and ions on a co-culture model for the gastrointestinal epithelium. AB - BACKGROUND: The increased incorporation of silver nanoparticles (Ag NPs) into consumer products makes the characterization of potential risk for humans and other organisms essential. The oral route is an important uptake route for NPs, therefore the study of the gastrointestinal tract in respect to NP uptake and toxicity is very timely. The aim of the present study was to evaluate the effects of Ag NPs and ions on a Caco-2/TC7:HT29-MTX intestinal co-culture model with mucus secretion, which constitutes an important protective barrier to exogenous agents in vivo and may strongly influence particle uptake. METHODS: The presence of the mucus layer was confirmed with staining techniques (alcian blue and toluidine blue). Mono and co-cultures of Caco-2/TC7 and HT29-MTX cells were exposed to Ag NPs (Ag 20 and 200 nm) and AgNO3 and viability (alamar blue), ROS induction (DCFH-DA assay) and IL-8 release (ELISA) were measured. The particle agglomeration in the media was evaluated with DLS and the ion release with ultrafiltration and ICP-MS. The effects of the Ag NPs and AgNO3 on cells in co culture were studied at a proteome level with two-dimensional difference in gel electrophoresis (2D-DIGE) followed by Matrix Assisted Laser Desorption Ionization - Time Of Flight/ Time Of Flight (MALDI-TOF/TOF) mass spectrometry (MS). Intracellular localization was assessed with NanoSIMS and TEM. RESULTS: The presence of mucus layer led to protection against ROS and decrease in IL-8 release. Both Ag 20 and 200 nm NPs were taken up by the cells and Ag NPs 20 nm were mainly localized in organelles with high sulfur content. A dose- and size dependent increase in IL-8 release was observed with a lack of cytotoxicity and oxidative stress. Sixty one differentially abundant proteins were identified involved in cytoskeleton arrangement and cell cycle, oxidative stress, apoptosis, metabolism/detoxification and stress. CONCLUSIONS: The presence of mucus layer had an impact on modulating the induced toxicity of NPs. NP-specific effects were observed for uptake, pro-inflammatory response and changes at the proteome level. The low level of overlap between differentially abundant proteins observed in both Ag NPs and AgNO3 treated co-culture suggests size-dependent responses that cannot only be attributed to soluble Ag. PMID- 26888337 TI - Accelerating Gas Adsorption on 3D Percolating Carbon Nanotubes. AB - In the field of electronic gas sensing, low-dimensional semiconductors such as single-walled carbon nanotubes (SWCNTs) can offer high detection sensitivity owing to their unprecedentedly large surface-to-volume ratio. The sensitivity and responsivity can further improve by increasing their areal density. Here, an accelerated gas adsorption is demonstrated by exploiting volumetric effects via dispersion of SWCNTs into a percolating three-dimensional (3D) network in a semiconducting polymer. The resultant semiconducting composite film is evaluated as a sensing membrane in field effect transistor (FET) sensors. In order to attain reproducible characteristics of the FET sensors, a pulsed-gate-bias measurement technique is adopted to eliminate current hysteresis and drift of sensing baseline. The rate of gas adsorption follows the Langmuir-type isotherm as a function of gas concentration and scales with film thickness. This rate is up to 5 times higher in the composite than only with an SWCNT network in the transistor channel, which in turn results in a 7-fold shorter time constant of adsorption with the composite. The description of gas adsorption developed in the present work is generic for all semiconductors and the demonstrated composite with 3D percolating SWCNTs dispersed in functional polymer represents a promising new type of material for advanced gas sensors. PMID- 26888338 TI - A comparison of the efficacy of piperacillin-tazobactam and cefoperazone sulbactam therapies in the empirical treatment of patients with febrile neutropenia. AB - OBJECTIVE: Empirical antibiotic therapy in neutropenic patients presenting with fever plays a significant role in reducing mortality related to infection. Empirical therapies with broad-spectrum intravenous bactericidal, anti pseudomonal antibiotics are accepted treatments for febrile neutropenic patients. The aim of this study was to compare the efficacy of piperacillin-tazobactam (PIP TAZO) and cefoperozone-sulbactam (CS) therapies in adult patients with haematological malignancies presenting with neutropenic fever in a prospective study design. METHODS: Patients with haematological malignancies (leukaemia, lymphoma, multiple myeloma, and myelodysplastic syndrome) were recruited from June 2010-May 2013. Participants were over 18 years old, with an absolute neutrophil count (ANC) of less than 500/mm3 following chemotherapy or expected to have an ANC less than 500/mm3 in the first 48 h post-chemotherapy, and with an oral body temperature >= 38.3 degrees C at a single measurement or 38.0 degrees C after 1-h monitoring. Patients were randomised to the two treatment groups. The initial empirical therapy comprised PIP-TAZO (4.5 g/6 h/day, IV) and CS (2 g/8 h/day, IV). RESULTS: The overall success rate was 61% with CS and 49% with PIP TAZO (p =0.247). Factors affecting the treatment success included a neutrophil count <100/mm3, being in the relapse/refractory stage of malignancy, and the presence of a microbiologically documented infection (p <0.05). CONCLUSIONS: PIP TAZO and CS monotherapies are equally effective and safe for the empirical treatment of febrile neutropenic patients. PMID- 26888339 TI - [Knowledge and attitudes of healthcare workers towards a suspect case of Ebola virus disease]. AB - OBJECTIVE: The last outbreak of the Ebola virus disease, was a precedent to demonstrate the necessary training of healthcare personnel for possible eventualities of suspected cases of infectious diseases. It is required to study the level of qualification of healthcare workers in such situations. METHODS: Descriptive study using post-workshop survey of healthcare workers in a Valencian Community health department on acquired knowledge and skills after training. CONCLUSIONS: Healthcare personnel received an overall passing score on the post workshop survey, but with differences in occupational categories and different blocks of training. The ratings could be considered deficient in some cases. It should be reviewed periodically training health personnel and calibrate such training to the resources available for proper operation. PMID- 26888340 TI - [Bicytopenia due to parvovirus b19 infection in octogenarian: a case report]. PMID- 26888341 TI - Clarithromycin plus linezolid as a sequential therapy for implantable cardioverter-defibrillator infection caused by coagulase-negative staphylococci. PMID- 26888343 TI - Least-Squares Is Not the Only Yardstick for Estimating the Absorption Limit of an Infinitely Long Conjugated Chain from Spectra of Oligomers. PMID- 26888342 TI - Nurses' attitudes and perceived barriers to the reporting of medication administration errors. AB - AIMS: (1) To explore the attitudes and perceived barriers to reporting medication administration errors and (2) to understand the characteristics of - and nurses' feelings - about error reports. BACKGROUND: Under-reporting of medication administration errors is a global concern related to the safety of patient care. Understanding nurses' attitudes and perceived barriers to error reporting is the initial step to increasing the reporting rate. METHODS: A cross-sectional, descriptive survey with a self-administered questionnaire was completed by the nurses of a medical centre hospital in Taiwan. RESULTS: A total of 306 nurses participated in the study. Nurses' attitudes towards medication administration error reporting were inclined towards positive. The major perceived barrier was fear of the consequences after reporting. The results demonstrated that 88.9% of medication administration errors were reported orally, whereas 19.0% were reported through the hospital internet system. Self-recrimination was the common feeling of nurses after the commission of an medication administration error. CONCLUSIONS: Even if hospital management encourages errors to be reported without recrimination, nurses' attitudes toward medication administration error reporting are not very positive and fear is the most prominent barrier contributing to underreporting. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should establish anonymous reporting systems and counselling classes to create a secure atmosphere to reduce nurses' fear and provide incentives to encourage reporting. PMID- 26888344 TI - Nanoparticles at SEA: Seeding, Etching, and Applications. PMID- 26888345 TI - Non-Saccharomyces and Saccharomyces strains co-fermentation increases acetaldehyde accumulation: effect on anthocyanin-derived pigments in Tannat red wines. AB - During fermentation, Saccharomyces cerevisiae releases into the medium secondary metabolic products, such as acetaldehyde, able to react with anthocyanins, producing more stable derived pigments. However, very limited reports are found about non-Saccharomyces effects on grape fermentation. In this study, six non Saccharomyces yeast strains, belonging to the genera Metschnikowia and Hanseniaspora, were screened for their effect on red wine colour and wine-making capacity under pure culture conditions and mixed with Saccharomyces. An artificial red grape must was prepared, containing a phenolic extract of Tannat grapes that allows monitoring changes of key phenol parameters during fermentation, but without skin solids in the medium. When fermented in pure cultures, S. cerevisiae produced higher concentrations of acetaldehyde and vitisin B (acetaldehyde reaction-dependent) compared to M. pulcherrima M00/09G, Hanseniaspora guillermondii T06/09G, H. opuntiae T06/01G, H. vineae T02/05F and H. clermontiae (A10/82Fand C10/54F). However, co-fermentation of H. vineae and H. clermontiae with S. cerevisiae resulted in a significantly higher concentration of acetaldehyde compared with the pure S. cerevisiae control. HPLC-DAD-MS analysis confirmed an increased formation of vitisin B in co-fermentation treatments when compared to pure Saccharomyces fermentation, suggesting the key role of acetaldehyde. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888346 TI - Salivary epigenetic biomarkers in head and neck squamous cell carcinomas. AB - The early detection of head and neck squamous cell carcinoma (HNSCC) continues to be a challenge to the clinician. Saliva as a diagnostic medium carries significant advantages including its close proximity to the region of interest, ease of collection and noninvasive nature. While the identification of biomarkers continues to carry significant diagnostic and prognostic utility in HNSCC, epigenetic alterations present a novel opportunity to serve this purpose. With the developments of novel and innovative technologies, epigenetic alterations are now emerging as attractive candidates in HNSCC. As such, this review will focus on two commonly aberrant epigenetic alterations: DNA methylation and microRNA expression in HNSCC and their potential clinical utility. Identification and validation of these salivary epigenetic biomarkers would not only enable early diagnosis but will also facilitate in the clinical management. PMID- 26888349 TI - ERA-NET NEURON: a network with emergent properties. PMID- 26888350 TI - More than just a headache. PMID- 26888347 TI - Image processing methods to elucidate spatial characteristics of retinal microglia after optic nerve transection. AB - Microglia are the mononuclear phagocytes with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions. In optical nerve transection model of the retina, the retrograde degeneration of retinal ganglion cells induces microglial activations to a unique morphology termed rod microglia. A few studies described the rod microglia in the cortex and retina; however, the spatial characteristic of rod microglia is not fully understood. In this study, we built a mathematical model to characterize the spatial trait of rod microglia. In addition, we developed a Matlab-based image processing pipeline that consists of log enhancement, image segmentation, mathematical morphology based cell detection, area calculation and angle analysis. This computer program provides researchers a powerful tool to quickly analyze the spatial trait of rod microglia. PMID- 26888348 TI - Age-Dependent Changes in Pb Concentration in Human Teeth. AB - The result of exposure to Pb is its accumulation in mineralized tissues. In human body, they constitute a reservoir of approx. 90 % of the Pb reserve. The conducted research aimed at determining the accumulation of Pb in calcified tissues of permanent teeth. The concentration of Pb in 390 samples of teeth taken from a selected group of Polish people was determined using the AAS method. Average concentration of Pb in teeth amounted to 14.3 +/- 8.18 MUg/g, range of changes: 2.21-54.8 MUgPb/g. Accumulation of Pb in human body was determined based on changes in Pb concentration in teeth of subjects aged 13-84 years. It was found that in calcified tissues of teeth, the increase in concentration of Pb that occurs with age is a statistically significant process (p = 0.02, the ANOVA Kruskal-Wallis test). It was determined that the annual increase in concentration of Pb in tissues of teeth is approx. 0.1 MUg/g. Moreover, a different course of changes in Pb concentration in tissues of teeth in people born in different years was observed. The level of Pb concentration in teeth of the oldest subjects (>60 years) decreased for those born in the 1930s compared to those in the 1950s. Teeth from younger persons (<60 years) were characterized by an increasing level of Pb concentration. The analysis of changes of Pb indicates that for low exposure, a relatively greater accumulation of Pb concentration in calcified tissues of teeth can occur. PMID- 26888351 TI - Orrin Devinsky: breaking through treatment-resistant epilepsy. PMID- 26888352 TI - Dante Alighieri's narcolepsy. PMID- 26888353 TI - Nanna Finnerup. PMID- 26888356 TI - Association of Thrombomodulin Gene Polymorphisms with Susceptibility to Atherosclerotic Diseases: A Meta-Analysis. AB - Previous studies have proved that the dysfunction of thrombomodulin (TM) plays an important role in the pathogenesis of atherosclerotic diseases. In order to reveal their inherent relationship, we conducted a meta-analysis to uncover the association between two polymorphisms -33G/A and Ala455Val (c.1418C>T) in the TM gene and atherosclerotic diseases. We carried out a systematic search in PubMed, Science Direct, BIOSIS Previews, SpringerLink, the Cochrane library, the Chinese National Knowledge Infrastructure, the Chinese Biomedical Database, the Wei Pu database, and the Wanfang Database. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed to show the association. We included 22 eligible studies which involved 5472 patients and 7786 controls. There were statistically significant associations between -33G/A polymorphisms in TM and the MI group under the Allele and Recessive models in Asians (G vs. A: OR = 0.67, 95%CI = 0.56 0.78, P < 0.00001; GG vs. GA+AA: OR = 0.66, 95%CI = 0.56-0.78, P < 0.00001). However, these findings of the overall and subgroups showed that Ala455Val polymorphisms did not have any relationship with atherosclerotic diseases. After Bonferroni correction, the above associations remained statistically significant. This meta-analysis provides robust evidence of association between the -33G/A polymorphism in the TM gene and the risk of myocardial infarction in Asians. The A allele may increase the incidence of MI in Asians. However, the Ala455Val variant was not associated with atherosclerotic risk. Further studies with adequate sample size are needed to verify our findings. PMID- 26888358 TI - Chlorine as a geobarometer for alkaline magmas: Evidence from a systematic study of the eruptions of Mount Somma-Vesuvius. AB - Defining the magma storage conditions of a volcanic system is a major goal in modern volcanology due to its direct implications for the style of a possible eruption, and thus on the associated risk of any crisis and the necessary management and mitigation strategies. Below 200 MPa and at equivalent depths, the strongly non-ideal behaviour of the H-C-O-S-Cl-F system in the silicate melt causes unmixing of the fluid phase to form an H2O-rich vapour and a hydrosaline phase in equilibrium with the silicate melt, both responsible for buffering the chlorine (Cl) concentration. Following this equilibrium, the Cl concentration in melts may be used as a geobarometer for alkaline magmas. Systematic application of this method to the main explosive eruptions of Mount Somma-Vesuvius highlights two main magma ponding zones, at ~180-200 and ~100 MPa. At these pressures, the maximum pre-eruptive H2O contents for the different magma compositions can be estimated; the results obtained, largely in agreement with the current literature, therefore confirm the validity of the method. The Cl geobarometer may help scientists to define the variation of the magmatic reservoir location through time and thus provide strong constraints on pre-eruptive conditions, which are of utmost importance for volcanic crisis management. PMID- 26888355 TI - Mesenchymal stem cell-based gene therapy for erectile dysfunction. AB - Despite the overwhelming success of PDE5 inhibitor (PDE5I), the demand for novel pharmacotherapeutic and surgical options for ED continues to rise owing to the increased proportion of elderly individuals in the population, in addition to the growing percentage of ED patients who do not respond to PDE5I. Surgical treatment of ED is associated with many complications, thus warranting the need for nonsurgical therapies. Moreover, none of the above-mentioned treatments essentially corrects, cures or prevents ED. Although gene therapy is a promising option, many challenges and obstacles such as local inflammatory response and random transgene expression, in addition to other safety issues, limit its use at the clinical level. The use of stem cell therapy alone also has many shortcomings. To overcome these inadequacies, many scientists and clinicians are investigating new gene and stem cell therapies. PMID- 26888359 TI - Creating a zero-order resonator using an optical surface transformation. AB - A novel zero-order resonator has been designed by an optical surface transformation (OST) method. The resonator proposed here has many novel features. Firstly, the mode volume can be very small (e.g. in the subwavelength scale). Secondly, the resonator is open (no reflecting walls are utilized) and resonant effects can be found in a continuous spectrum (i.e. a continuum of eigenmodes). Thirdly, we only need one homogenous medium to realize the proposed resonator. The shape of the resonator can be a ring structure of arbitrary shape. In addition to the natural applications (e.g. optical storage) of an optical resonator, we also suggest some other applications of our novel optical open resonator (e.g. power combination, squeezing electromagnetic energy in the free space). PMID- 26888357 TI - Integrated molecular, physiological and in silico characterization of two Halomonas isolates from industrial brine. AB - Two haloalkaliphilic bacteria isolated from industrial brine solutions were characterized via molecular, physiological, and in silico metabolic pathway analyses. Genomes from the organisms, designated Halomonas BC1 and BC2, were sequenced; 16S ribosomal subunit-based phylogenetic analysis revealed a high level of similarity to each other and to Halomonas meridiana. Both strains were moderate halophiles with near optimal specific growth rates (>=60 % MU max) observed over <0.1-5 % (w/v) NaCl and pH ranging from 7.4 to 10.2. Isolate BC1 was further characterized by measuring uptake or synthesis of compatible solutes under different growth conditions; in complex medium, uptake and accumulation of external glycine betaine was observed while ectoine was synthesized de novo in salts medium. Transcriptome analysis of isolate BC1 grown on glucose or citrate medium measured differences in glycolysis- and gluconeogenesis-based metabolisms, respectively. The annotated BC1 genome was used to build an in silico, genome scale stoichiometric metabolic model to study catabolic energy strategies and compatible solute synthesis under gradients of oxygen and nutrient availability. The theoretical analysis identified energy metabolism challenges associated with acclimation to high salinity and high pH. The study documents central metabolism data for the industrially and scientifically important haloalkaliphile genus Halomonas. PMID- 26888361 TI - The chiasmatic recess of the third ventricle: delineation with magnetic resonance imaging. AB - PURPOSE: The chiasmatic recess (CR) is a small, downward extension in the most rostral third ventricle. Few studies have highlighted its morphology. Accordingly, we explored the CR using magnetic resonance imaging. METHODS: A total of 104 patients were enrolled in this study. Magnetic resonance imaging examinations were performed in axial and sagittal sections. Imaging data were obtained as thin-sliced, seamless sections. RESULTS: The CR was clearly identified in 98 % of axial and 96 % of sagittal sections. The lamina terminalis was delineated as a membranous structure with homogenous thickness. The CR was consistently delineated as a smoothly tapering, cerebrospinal fluid-filled space. The number of axial images required to encompass the entire CR was 1 slice for 1.9 % of samples, 2 for 32.7 %, 3 for 49 %, 4 for 12.5 %, 5 for 1 %, and 6 for 1 %. On axial view, the CR generally presented as a long horizontal ellipse. On sagittal view, the CR showed variable shape and length. The optic chiasm-lamina terminalis angle, formed by the upper surface of the optic chiasm and inner surface of the lamina terminalis and measured on midsagittal sections, showed considerable variability. CONCLUSIONS: The CR is a hollow structure with various contours. Recognition of the morphological characteristics of the CR and lamina terminalis may be helpful for safe perforation of the lamina terminalis. Magnetic resonance imaging is useful for exploring the CR. PMID- 26888360 TI - Targeting the poorest in a performance-based financing programme in northern Cameroon. AB - Performance-Based Financing (PBF) is a promising approach to improve health system performance in developing countries, but there are concerns that it may inadequately address inequalities in access to care. Incentives for reaching the poor may prove beneficial, but evidence remains limited. We evaluated a system of targeting the poorest of society ('indigents') in a PBF programme in Cameroon, examining (under)coverage, leakage and perceived positive and negative effects. We conducted a documentation review, 59 key informant interviews and 33 focus group discussions with community members (poor and vulnerable people-registered as indigents and those not registered as such). We found that community health workers were able to identify very poor and vulnerable people with a minimal chance of leakage to non-poor people. Nevertheless, the targeting system only reached a tiny proportion (<=1%) of the catchment population, and other poor and vulnerable people were missed. Low a priori set objectives and implementation problems-including a focus on easily identifiable groups (elderly, orphans), unclarity about pre-defined criteria, lack of transport for identification and insufficient motivation of community health workers-are likely to explain the low coverage. Registered indigents perceived improvements in access, quality and promptness of care, and improvements in economic status and less financial worries. However, lack of transport and insufficient knowledge about the targeting benefits, remained barriers for health care use. Negative effects of the system as experienced by indigents included negative reactions (e.g. jealousy) of community members. In conclusion, a system of targeting the poorest of society in PBF programmes may help reduce inequalities in health care use, but only when design and implementation problems leading to substantial under coverage are addressed. Furthermore, remaining barriers to health care use (e.g. transport) and negative reactions of other community members towards indigents deserve attention. PMID- 26888363 TI - Strategies to deal with comorbid physical illness in psychosis. AB - Individuals with serious mental illnesses such as psychosis still experience higher mortality rates than the general population, decades after data have linked the gap to increased rates of physical illness, delayed diagnosis, low treatment rates and worse outcomes from treatment received. The nature of the relationship between psychosis and comorbid physical illness is complex. Multiple strategies directed at different levels of disease process, health care systems and stakeholder culture are likely required to make sustained progress in reducing the mortality gap. Evidence for strategies that effectively reduce the burden of physical co-morbidity and lead to improved health outcomes are still in their infancy but growing at a reassuringly fast rate. This editorial considers the existing evidence base and makes suggestions for the development and future direction of this urgent research agenda and how this knowledge can be implemented in clinical practice. PMID- 26888362 TI - alpha-methylacyl-CoA racemase (AMACR) expression in chordomas differentiates them from chondrosarcomas. AB - AIMS: Chordomas and chondrosarcomas are malignant mesenchymal tumours with overlapping morphological and immunohistochemical (IHC) characteristics. Our aim was to evaluate the IHC expression of alpha-methylacyl-CoA racemase (AMACR/P504S), beta-catenin and E-cadherin in chordomas relative to chondrosarcomas and assess the utility of these markers for differential diagnosis. METHODS: Archival sections of 18 chordomas, 19 chondrosarcomas and 10 mature cartilage samples were immunostained and scored for AMACR, beta-catenin and E-cadherin and the relative differential capacity of each marker was calculated. In addition, AMACR mRNA level was assessed in 5 chordomas by RT-PCR and evaluated by comparative CT method. RESULTS: AMACR and beta-catenin stained 88.9% and 94.1% of the chordomas respectively, 21.1% and 10.5% of the chondrosarcomas correspondingly and none of the mature cartilage samples. E cadherin stained positively 82.4% of the chordomas, 36.8% of the chondrosarcomas and 42.9% of the mature cartilage cases. Both AMACR and beta-catenin showed statistically significant difference between chordomas and chondrosarcomas (p < 0.001 for both), unlike E-cadherin. AMACR was detected at the mRNA level. CONCLUSIONS: AMACR is expressed in most of the chordomas but only in a minority of chondrosarcomas. AMACR may serve as IHC marker of chordoma with differentiating ability comparable to that of beta-catenin. PMID- 26888365 TI - Broadening the absorption bandwidth of metamaterial absorbers by transverse magnetic harmonics of 210 mode. AB - By investigating a square-shaped metamaterial structure we discover that wave diffraction at diagonal corners of such a structure excites transverse magnetic harmonics of 210 mode (TM210 harmonics). Multi-layer overlapping and deliberately regulating period length between adjacent unit cells can significantly enhance TM210 harmonics, leading to a strong absorption waveband. On such a basis, a design strategy is proposed to achieve broadband, thin-thickness multi-layered metamaterial absorbers (MMAs). In this strategy big pyramidal arrays placed in the "white blanks" of a chessboard exhibit two isolated absorption bands due to their fundamental and TM210 harmonics, which are further connected by another absorption band from small pyramidal arrays in the "black blanks" of the chessboard. The as-designed MMA at a total thickness (h) of 4.36 mm shows an absorption of above 0.9 in the whole frequency range of 7-18 GHz, which is 38% broader with respect to previous design methods at the same h. This strategy provides an effective route to extend the absorption bandwidth of MMAs without increasing h. PMID- 26888364 TI - Elevated Low-Shear Blood Viscosity is Associated with Decreased Pulmonary Blood Flow in Children with Univentricular Heart Defects. AB - After the Fontan procedure, patients with univentricular hearts can experience long-term complications due to chronic low-shear non-pulsatile pulmonary blood flow. We sought to evaluate hemorheology and its relationship to hemodynamics in children with univentricular hearts. We hypothesized that low-shear blood viscosity and red blood cell (RBC) aggregation would be associated with increased pulmonary vascular resistance (PVR) and decreased pulmonary blood flow (PBF). We performed a cross-sectional analysis of 62 children undergoing cardiac catheterization-20 with isolated atrial septal defect (ASD), 22 status post Glenn procedure (Glenn), and 20 status post Fontan procedure (Fontan). Shear-dependent blood viscosity, RBC aggregation and deformability, complete blood count, coagulation panel, metabolic panel, fibrinogen, and erythrocyte sedimentation rate were measured. PVR and PBF were calculated using the Fick equation. Group differences were analyzed by ANOVA and correlations by linear regression. Blood viscosity at all shear rates was higher in Glenn and Fontan, partially due to normocytic anemia in ASD. RBC aggregation and deformability were similar between all groups. Low-shear viscosity negatively correlated with PBF in Glenn and Fontan only (R (2) = 0.27, p < 0.001); it also negatively correlated with pulmonary artery pressure in Glenn (R (2) = 0.15, p = 0.01), and positively correlated with PVR in Fontan (R (2) = 0.28, p = 0.02). Our data demonstrate that elevated low-shear blood viscosity is associated with negative hemodynamic perturbations in a passive univentricular pulmonary circulation, but not in a pulsatile biventricular pulmonary circulation. PMID- 26888366 TI - Energy expenditure in critically ill patients estimated by population-based equations, indirect calorimetry and CO2-based indirect calorimetry. AB - BACKGROUND: Indirect calorimetry (IC) is the reference method for measurement of energy expenditure (EE) in mechanically ventilated critically ill patients. When IC is unavailable, EE can be calculated by predictive equations or by VCO2-based calorimetry. This study compares the bias, quality and accuracy of these methods. METHODS: EE was determined by IC over a 30-min period in patients from a mixed medical/postsurgical intensive care unit and compared to seven predictive equations and to VCO2-based calorimetry. The bias was described by the mean difference between predicted EE and IC, the quality by the root mean square error (RMSE) of the difference and the accuracy by the number of patients with estimates within 10 % of IC. Errors of VCO2-based calorimetry due to choice of respiratory quotient (RQ) were determined by a sensitivity analysis, and errors due to fluctuations in ventilation were explored by a qualitative analysis. RESULTS: In 18 patients (mean age 61 +/- 17 years, five women), EE averaged 2347 kcal/day. All predictive equations were accurate in less than 50 % of the patients with an RMSE >= 15 %. VCO2-based calorimetry was accurate in 89 % of patients, significantly better than all predictive equations, and remained better for any choice of RQ within published range (0.76-0.89). Errors due to fluctuations in ventilation are about equal in IC and VCO2-based calorimetry, and filtering reduced these errors. CONCLUSIONS: This study confirmed the inaccuracy of predictive equations and established VCO2-based calorimetry as a more accurate alternative. Both IC and VCO2-based calorimetry are sensitive to fluctuations in respiration. PMID- 26888368 TI - Multi-vessel disease and CZT SPECT. Comparison with coronary angiography. PMID- 26888370 TI - Safety of stress testing in patients with elevated cardiac biomarkers: Are all modalities created equal? PMID- 26888369 TI - Improving cardiac SPECT accuracy: Old robustness for a new gold standard. PMID- 26888371 TI - Incidental detection of bronchial carcinoid on Tc-99m sestamibi SPECT/CT myocardial perfusion scintigraphy. AB - Technetium-99m sestamibi MPS is a commonly employed imaging study for myocardial perfusion; however, incidental extracardiac sestamibi uptake requires further evaluation, and the tracer uptake in the thorax/mediastinum may be pathological. The authors present a case of significant extra-cardiac uptake seen on stress MPS images helping in the incidental detection of bronchial carcinoid. PMID- 26888372 TI - Software-dependent processing variability in SPECT functional parameters: Clinical implications. PMID- 26888373 TI - Relationship between residual viable myocardium and LV remodeling post-MI: Only part of the story. PMID- 26888374 TI - Genetic instability of Japanese encephalitis virus cDNA clones propagated in Escherichia coli. AB - The genetic instability of Flavivirus cDNA clones in transformed bacteria is a common phenomenon. Herein, a cDNA fragment of the nucleotide (nt) 1-2913 of the genome of a flavivirus, Japanese encephalitis virus (JEV), was used to investigate factors that caused the instability of cDNA clones. Several cDNA fragments with different 5'- or 3'-termini of the 2913-nt cDNA were obtained by PCR amplification or restriction enzyme digestion and cloned into a pCR-Blunt II TOPO vector. All the cDNA fragments were stably propagated at 25 degrees C. However, the 5'-untranslated region and half of the 3'-E gene could cause the instability of the 2913-nt cDNA at 37 degrees C. The 5'-terminus sequences of the 2913-nt fragment were subjected to testing of the prokaryotic promoter activity by luciferase assay and Western blot. The sequences of 54-120 nt of the JEV genome exhibited high prokaryotic promoter activity at 37 degrees C, and the activity declined markedly at 25 degrees C. These findings revealed that the high prokaryotic promoter activity of the 54-120 nt sequences of the JEV genome together with expression of JEV structural genes determined the instability of a JEV cDNA clone. Growth at room temperature may reduce the prokaryotic promoter activity of 5'-sequences of the JEV genome and could represent an effective way to improve the stability of flavivirus cDNA clones in host bacteria. PMID- 26888375 TI - Evaluation of the potential synergism of imatinib-related poly kinase inhibitors using growth factor stimulated proteoglycan synthesis as a model response. AB - INTRODUCTION: Tyrosine kinase inhibitors were the first class of smart drugs being specifically designed to inhibit a disease causing target. There is a very important but unresolved question as whether or not the overall therapeutic role of an individual tinib results from an action at its primary target, a single most likely, tyrosine kinase, or from the combined or aggregate action at the multiple targets which each tinib addresses. METHODS: We selected a series of ten tinibs (gefitinib, sunitinib, lapatinib, erlotinib, imatinib, sorafenib, axitinib, vanitinib, bosutinib, dasatinib) with various known targets and investigated their activities in the inhibition of proteoglycan synthesis and GAG hyperelongation stimulated by a tyrosine kinase receptor agonist, platelet derived growth factor (PDGF) and for contrast, a serine/threonine kinase receptor agonist, TGF beta and some downstream signalling pathways. RESULTS: The inhibitory activity varied from little to total inhibition. The actions of the tinibs were directed more towards inhibition of the tyrosine kinase, PDGF receptor signalling pathway compared to the TGF beta. CONCLUSION: There was no suggestion of any synergistic effect arising from inhibition of multiple kinases as the most potent compound, dasatinib, is known to inhibit the broadest spectrum of kinases. PMID- 26888376 TI - Searching for consensus among physicians involved in the management of sick listed workers in the Belgian health care sector: a qualitative study among practitioners and stakeholders. AB - BACKGROUND: In Belgium, the management of sick leave involves general practitioners (GPs), occupational health physicians (OPs) and social insurance physicians (SIPs). A dysfunctional relationship among these physicians can impede a patient's ability to return to work. The objective of this study was to identify ways to improve these physicians' mutual collaboration. METHODS: Two consensus techniques were successively performed among the three professional groups. Eight nominal groups (NGs) gathered 74 field practitioners, and a two round Delphi process involved 32 stakeholders. RESULTS: From the results, it appears that two areas (reciprocal knowledge and evolution of the legal and regulatory framework) are objects of consensus among the three medical group that were surveyed. Information transfer, particularly electronic transfer, was stressed as an important way to improve. The consensual proposals regarding interdisciplinary collaboration indicate specific and practical changes to be implemented when professionals are managing workers who are on sick leave. The collaboration process appeared to be currently more problematic, but the participants correctly identified the need for common training. CONCLUSIONS: The three physician groups all agree regarding several inter-physician collaboration proposals. The study also revealed a latent conflict situation among the analysed professionals that can arise from a lack of mutual recognition. Practical changes or improvements must be included in an extended framework that involves the different determinants of interdisciplinary collaboration that are shown by theoretical models. Collaboration is a product of the actions and behaviours of various partners, which requires reciprocal knowledge and trust; collaboration also implies political and economic structures that are led by public health authorities. PMID- 26888377 TI - A new tropane alkaloid from the leaves of Erythroxylum subsessile isolated by pH zone-refining counter-current chromatography. AB - Tropane alkaloids are bioactive metabolites with great importance in the pharmaceutical industry and the most important class of natural products found in the Erythroxylum genus. However, these compounds are usually separated by traditional chromatographic techniques, in which the sample is progressively purified in multiple chromatographic steps, resulting in a time- and solvent consuming procedure. In this work we present the isolation of a novel alkaloid, 6beta,7beta-dibenzoyloxytropan-3alpha-ol, together with the two known 3alpha benzoyloxynortropan-6beta-ol and 3alpha,6beta-dibenzoyloxytropane alkaloids, directly from the crude alkaloid fraction from the leaves of Erythroxylum subsessile, by using a single run pH-zone-refining counter-current chromatography method. The ethyl acetate/water (1:1, v/v) biphasic solvent system with triethylamine and HCl as retention and eluter agents, respectively, was used to isolate tropane alkaloids for the first time. The structures of the isolated alkaloids were elucidated by spectroscopic methods. PMID- 26888378 TI - Time to abandon three-phase trials? PMID- 26888379 TI - Pretransplant uric acid levels may be predictive for prognosis of renal transplant donors. AB - BACKGROUND: The living kidney donor counseling prior to the operation may be helpful to learn how to properly care for the remaining single kidney for the rest of their lives. Worsening kidney function is associated with elevated serum uric acid (UA) levels. In this study, we compared the baseline laboratory findings of renal transplant donors with their follow-up laboratory values. METHODS: The study consisted of 173 adult donors including 91 females and 82 males with a mean age of 46.82 +/- 11.31 years. The follow-up clinical and laboratory examinations were performed on the third day at the end of the first and the sixth months of the surgery. According to donor's creatinine levels we constituted two groups: high creatinine and normal creatinine. RESULTS: Patients within the high creatinine group had significantly higher mean serum UA levels when compared with the normal creatinine group. In multivariate analysis, among the other effective variables, UA level alone was found to be the most effective parameter predicting the post-transplant creatinine levels (p = 0.004, odds ratio: 12.4, 95% CI: 2.3-68.3) at sixth month post-transplantation. In the ROC analysis for the effects of UA, the following cutoff values were found: >6 mg/dL in men (sensitivity 81.3%, specificity 76.9%, positive predictive value 89.7%, negative predictive value 62.5%, accuracy 80%) and >=5 mg/dL in women (sensitivity 72.2, specificity 74.4%, positive predictive value 89.7%, negative predictive value 62.5%, accuracy: 73.7%). CONCLUSION: Pretransplant serum UA levels can give important clues regarding the renal functions of the donors during the postoperative period. PMID- 26888380 TI - Measuring the short-term impact of fluoridation cessation on dental caries in Grade 2 children using tooth surface indices. AB - OBJECTIVES: To examine the short-term impact of fluoridation cessation on children's caries experience measured by tooth surfaces. If there is an adverse short-term effect of cessation, it should be apparent when we focus on smooth tooth surfaces, where fluoride is most likely to have an impact for the age group and time frame considered in this study. METHODS: We examined data from population-based samples of school children (Grade 2) in two similar cities in the province of Alberta, Canada: Calgary, where cessation occurred in May 2011 and Edmonton where fluoridation remains in place. We analysed change over time (2004/2005 to 2013/2014) in summary data for primary (defs) and permanent (DMFS) teeth for Calgary and Edmonton, for all tooth surfaces and smooth surfaces only. We also considered, for 2013/2014 only, the exposed subsample defined as lifelong residents who reported usually drinking tap water. RESULTS: We observed, across the full sample, an increase in primary tooth decay (mean defs - all surfaces and smooth surfaces) in both cities, but the magnitude of the increase was greater in Calgary (F-cessation) than in Edmonton (F-continued). For permanent tooth decay, when focusing on smooth surfaces among those affected (those with DMFS>0), we observed a non-significant trend towards an increase in Calgary (F-cessation) that was not apparent in Edmonton (F-continued). CONCLUSIONS: Trends observed for primary teeth were consistent with an adverse effect of fluoridation cessation on children's tooth decay, 2.5-3 years post-cessation. Trends for permanent teeth hinted at early indication of an adverse effect. It is important that future data collection efforts in the two cities be undertaken, to permit continued monitoring of these trends. PMID- 26888381 TI - Human uterus transplantation in focus. AB - INTRODUCTION: Uterus transplantation (UTx) is introduced as the first treatment for absolute uterine factor infertility (AUFI), affecting 1:500 fertile aged women. This review presents potential patients, research and human UTx cases. SOURCES OF DATA: Published articles and our research experience. AREAS OF AGREEMENT: The first UTx live births in 2014 established UTx as a possible treatment for AUFI. This was proceeded by 15 years of systematic research. AREAS OF CONTROVERSY: Is a deceased donor UTx as effective as the proven successful live donor UTx?. GROWING POINTS: Human UTx trials will accumulate data on risks, effectiveness and long-term consequences for donors, recipients and children. These should also include aspects of quality of life, psychological well-being and cognitive/neuropsychiatric development of children. AREAS TIMELY FOR DEVELOPING RESEARCH: All new activities in human UTx within the coming years should be conducted as prospective observational studies, and data should also be collected within an international registry. PMID- 26888384 TI - [Histologic subtyping and clinicopathologic features of papillary renal cell carcinoma]. AB - OBJECTIVE: To study the morphologic characteristics and prognostic significance of 2 histologic subtypes of papillary renal cell carcinoma (PRCC). METHODS: A series of 48 tumors previously diagnosed as PRCC during the period from 2003 to 2013 were evaluated. All available slides were reviewed and 39 cases were confirmed to be PRCC. The detailed histomorphologic features were evaluated. The tumors were subtyped using the WHO classification and a novel mechanism suggested in recent literature, with prognostic correlation. Type 1 PRCC was assigned for tumors demonstrating simple cuboidal epithelium, irrespective of nuclear grade or other histomorphologic features. Tumors demonstrating cellular pseudostratification and high-grade nuclei were classified as type 2 PRCC. RESULTS: The novel subtyping mechanism was more practical and correlated with the outcome of patients. The scope of type 1 PRCC was expanded. Type 2 PRCC demonstrated high tumor stage and high nuclear grade, and was more likely to have perinephric/renal sinus fat invasion and sarcomatoid differentiation. Follow-up information was available in 32 patients, including 4 deaths in patients haboring type 2 PRCC. The survival rate of patients with type 2 PRCC was significantly lower than that of type 1 PRCC. CONCLUSIONS: The novel subtyping mechanism is more practical than WHO classification. Type 1 and type 2 PRCCs share many overlapping histomorphologic features. Type 2 PRCC is notably associated with worse prognosis. Recognizing the histomorphologic diversity of PRCC and classifying subtypes accurately are important in predicting the prognosis of patients with PRCC. PMID- 26888382 TI - Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study. AB - OBJECTIVE: To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes. DESIGN: Population based cohort. SETTING: Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom. PARTICIPANTS: A cohort of 972,384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014. MAIN OUTCOME MEASURES: Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models. RESULTS: During 2,024,441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking. CONCLUSIONS: In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs. PMID- 26888385 TI - [Diagnostic utility of S100A1, GLUT-1 and Caveolin-1 in renal tumors with oncocytic features: a comparative study]. AB - OBJECTIVE: To study the immunohistochemical expression of S100A1, GLUT-1 and Cavolin-1 and its diagnostic significance in renal tumors with oncocytic features. METHODS: Tissue microarray and immunohistochemical staining for S100A1, GLUT-1 and Cavolin-1 were carried out in 59 cases of renal tumors with oncocytic features, including 19 cases of renal oncocytoma, 15 cases of clear cell renal cell carcinoma (CCRCC) with eosinophilic cells, 11 cases of eosinophilic variant of chromophobe renal cell carcinoma, 7 cases of oncocytic papillary renal cell carcinoma and 7 cases of epithelioid angiomyolipoma. RESULTS: S100A1 was expressed in renal oncocytoma, with a positive propotion of 16/19 (including 14 cases showing widespread and strong positivity). On the other hand, the rate of expression of S100A1 was 2/11 in eosinophilic variant of chromophobe renal cell carcinoma, 10/15 in CCRCC with eosinophilic cells, 3/7 in oncocytic papillary renal cell carcinoma and 6/7 in epithelioid angiomyolipoma (P>0.05). The difference of S100A1 expression between renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma was statistically significant. GLUT-1 was located in cell membrane, with a positive rate of 13/15 in CCRCC with eosinophilic cells, 7/19 in renal oncocytoma, 4/7 (weak) in oncocytic papillary renal cell carcinoma, 1/11 in eosinophilic variant of chromophobe renal cell carcinoma and 0/7 in epithelioid angiomyolipoma. The rate of expression of Cav-1 was 6/15 in CCRCC with eosinophilic cells, 2/7 in oncocytic papillary renal cell carcinoma, 5/7 in epithelioid angiomyolipoma, 2/11 (weak) in eosinophilic variant of chromophobe renal cell carcinoma and 0/19 in renal oncocytoma. S100A1 showed high sensitivity and 50% specificity in the diagnosis of renal oncocytoma. GLUT-1 and Cav-1 showed high specificity and sensitivity in the diagnosis of CCRCC and epithelioid angiomyolipoma. CONCLUSIONS: S100A1 is widely expressed in various oncocytic renal neoplasms and helpful in differential diagnosis of renal oncocytoma from eosinophilic variant of chromophobe renal cell carcinoma, but not from other 3 oncocytic renal tumors. Overexpression of GLUT-1 can be used in distinction between CCRCC and renal oncocytoma. Cav-1 is widely expressed in CCRCC and epithelioid angiomyolipoma but not in renal oncocytoma. Cav-1 expression thus rules out renal oncocytoma. PMID- 26888386 TI - [Clinicopathologic characteristics of unusual rhabdoid glioblastoma]. AB - OBJECTIVE: To discuss the clinicopathologic features of rhabdoid glioblastoma of the brain and its differential diagnoses. METHODS: A 10-year-old and a 45-year old female both presented with gradually worsening headache, limbs twitch and blurred vision. MRI scan revealed a contrast enhancing tumor in the right temporal lobe and left cerebellum respectively. Both patients underwent tumor resection, followed by postoperative radiotherapy and chemotherapy. RESULTS: Microscopic examination of both tumors showed rhabdoid tumor cells with an eccentric nuclei and eosinophilic cytoplasms. Both tumors had areas of classic glioblastoma with microvascular proliferation and necrosis. Immunohistochemical staining showed the rhabdoid tumor cells were positive for vimentin diffusely and GFAP, EMA, CK focally. Integrase interactor (INI-1) was expressed in most tumor cells, but IDH1 R132H was not detected in both tumors. Fluorescence in situ hybridization revealed 1p/19q co-deletion in one case. One patient was alive without tumor recurrence after 16 months follow-up, the other patient died of intraspinal tumor dissemination 9 months after surgery. CONCLUSIONS: Rhabdoid glioblastoma is a rare glial cell tumor with specific rhabdoid tumor cells, a highly aggressive clinical course and poor prognosis. Combining histological features, a panel of selected immunostains including vimentin, GFAP, CK, EMA, SMA and INI-1 is helpful in making an accurate diagnosis for those diagnostically challenging cases with rhabdoid features in central nervous system. PMID- 26888383 TI - Musical Creativity "Revealed" in Brain Structure: Interplay between Motor, Default Mode, and Limbic Networks. AB - Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music. PMID- 26888387 TI - [Effects of p38 MAPK signaling pathway and aldose reductase on transforming growth factor-beta1 induced expression of fibronectin in cultured human mesangial cells]. AB - OBJECTIVE: To study the effects of p38 MAPK signaling pathway and aldose reductase (AR) on the transforming growth factor (TGF)-beta1-induced expression of fibronectin (FN). METHODS: Human mesangial cells (HMCs) were cultured, and transfected with pCDNA3-AR. AR gene silencing was induced by small interfering RNA (siRNA). AR expression in HMCs was examined by immunofluorescence analysis. RT-PCR and real-time PCR were performed to detect the mRNA expression of AR in the HMCs and Western blotting was used to detect the protein expression of AR, FN and p38. AR inhibitors (ARIs), Sorbinil and Zopolrestat were added and co incubated, followed by addition of TGF-beta1. Western blotting was used to document protein expression of FN and p38 mitogen-activated protein kinases (p38 MAPKs) in the HMCs. RESULTS: Immunofluorescence analysis showed a stronger expression of AR in HMCs transfected with AR than that of normal HMCs and HMCs transfected with blank vector. In comparison with normal HMCs and those transfected with blank vector, HMCs transfected with AR showed stronger protein expression of FN (P<0.05). After incubation of ARIs, protein expression of FN decreased in HMCs transfected with AR (P<0.05). After stimulation of TGF-beta1, FN protein expression increased in both normal HMCs and those transfected with AR (P<0.05). After preincubation with ARI, FN protein expression in HMCs transfected decreased significantly (P<0.05). After stimulation of TGF-beta1, naive HMCs showed increased expression of phosphor-p38. In contrast, HMCs preincubated with ARIs showed reduced expression of phosphor-p38, and HMCs transfected with AR showed increased expression of phosphor-p38 (P<0.05). CONCLUSIONS: AR regulates the expression of FN through the stimulation of TGF-beta1, which may involve the activation of p38-MAPK signaling pathway. AR may play a role in the pathogenesis of glomerulosclerosis. PMID- 26888389 TI - [Clinicopathological analysis on renal primitive neuroectodermal tumor]. PMID- 26888388 TI - [Impact of glycogen synthase kinase-3beta (GSK-3beta) inhibitor on Wnt and NF kappaB signal pathways in a rat model of diabetic nephropathy]. AB - OBJECTIVE: To explore the impact of glycogen synthase kinase-3beta (GSK-3beta) on Wnt and NF-kappaB pathways in a rat model of diabetic nephropathy (DN). METHODS: SD rats were randomly divided into normal control group (NC), DN model group (DM) and GSK-3beta inhibitor group (DI). Blood glucose and 24-hour urine protein were monitored in three groups. Renal tissue samples were stained by HE. The expression of GSK-3beta and NF-kappaB proteins was studied by immunohistochemistry. GSK-3beta and NF-kappaB mRNAs were detected by RT-qPCR. RESULTS: Ten weeks after STZ injection, the level of blood glucose increased significantly in DM group [(23.2+/-5.4) mmol/L] and DI group [(25.0+/-4.0) mmol/L], compared with NC group, and the level of 24-hour urinary protein increased significantly in DM group [(185.2+/-35.6) g/24 h] and DI group [(179.6+/-44.7) g/24 h], compared with NC group. Two weeks after LiCl injection, the level of blood glucose and 24-hour urinary protein decreased in DI group (17.6+/-2.1) mmol/L, (106.9+/-30.0) g/24 h], compared with DM Group. Compared with NC group, pathological changes of the kidney of DM group aggravated along with increased mRNA and protein expression of GSK-3beta and NF-kappaB. But the pathological changes of the kidney in DI group alleviated along with declined mRNA and protein expression of GSK-3beta and NF-kappaB as compared with DM group (all P<0.05). CONCLUSIONS: NF-kappaB protein expression positively correlates with the GSK3beta expression. Wnt and NF-kappaB signal pathways play an important role in the development of diabetic nephropathy. PMID- 26888390 TI - [Expression and clinical significance of TLR4 and NF-kappaB in cholesterol pneumonia]. PMID- 26888391 TI - [Mixed squamous cell and glandular papilloma: a report of 4 cases and review of literature]. PMID- 26888392 TI - [Analysis of in-situ mRNA expression of tumor biomarkers using formalin-fixed paraffin-embedded samples]. PMID- 26888393 TI - [Dense deposit disease in a young patient: report of a case]. PMID- 26888394 TI - [Synchronous pheochromocytoma and adrenal cortical adenoma in ipislateral adrenal gland: report of a case]. PMID- 26888395 TI - [Metastatic ovarian serous adenocarcinoma to clear cell renal cell carcinoma: report of a case]. PMID- 26888396 TI - [Metastatic clear cell renal cell carcinoma with sarcomatoid transformation: report of a case]. PMID- 26888397 TI - [Cryptogenic multifocal ulcerating and stenosing enteritis with pseudo membranous enteritis: report of a case]. PMID- 26888398 TI - [Epithelial Misplacement with High-Grade Dysplasia in a colonic adenoma: report of a case]. PMID- 26888399 TI - [Liponeurocytoma in petrous bone and supratentorial region of cerebellum: report of a case]. PMID- 26888400 TI - [Tall cell variant of papillary breast carcinoma: report of a case]. PMID- 26888401 TI - [Thymic Rosai-Dorfman disease: report of a case]. PMID- 26888403 TI - [Research progress on characteristic MYB-NFIB fusion gene in adenoid cystic carcinoma]. PMID- 26888402 TI - [Adult cystic renal tumors: diagnosis and differential diagnosis]. PMID- 26888405 TI - [Research progress on telepathology]. PMID- 26888404 TI - [Research advance on biologic significance of neurogenesis in tumor and its underlying molecular mechanisms]. PMID- 26888406 TI - Silver-catalyzed carboxylation. AB - Silver-catalyzed reactions are some of the important methodologies in organic chemistry. Since 2007, a new application of silver catalysts has been emerging. For the sequential carboxylation and cyclization of alkyne derivatives, such as propargyl alcohols and amines, using carbon dioxide, silver catalysts show significant reactivity under mild conditions unlike other transition metals. These developments have received much attention for the effective utilization of carbon dioxide in organic chemistry to synthesize heterocyclic compounds. Related silver-catalyzed C-C bond forming reactions with carbon dioxide have also provided the synthetic methods of the corresponding carboxylic acid derivatives. In this review, the recent studies of the silver-catalyzed carboxylation reactions using carbon dioxide are described. PMID- 26888407 TI - Effects of salinity and temperature on in vitro cell cycle and proliferation of Perkinsus marinus from Brazil. AB - Field and in vitro studies have shown that high salinities and temperatures promote the proliferation and dissemination of Perkinsus marinus in several environments. In Brazil, the parasite infects native oysters Crassostrea gasar and Crassostrea rhizophorae in the Northeast (NE), where the temperature is high throughout the year. Despite the high prevalence of Perkinsus spp. infection in oysters from the NE of Brazil, no mortality events were reported by oyster farmers to date. The present study evaluated the effects of salinity (5, 20 and 35 psu) and temperature (15, 25 and 35 degrees C) on in vitro proliferation of P. marinus isolated from a host (C. rhizophorae) in Brazil, for a period of up to 15 days and after the return to the control conditions (22 days; recovery). Different cellular parameters (changes of cell phase's composition, cell density, viability and production of reactive oxygen species) were analysed using flow cytometry. The results indicate that the P. marinus isolate was sensitive to the extreme salinities and temperatures analysed. Only the highest temperature caused lasting cell damage under prolonged exposure, impairing P. marinus recovery, which is likely to be associated with oxidative stress. These findings will contribute to the understanding of the dynamics of perkinsiosis in tropical regions. PMID- 26888408 TI - Drug testing in Europe: monitoring results of the Trans European Drug Information (TEDI) project. AB - Drug testing is a harm reduction strategy that has been adopted by certain countries in Europe. Drug users are able to hand in their drugs voluntarily for chemical analysis of composition and dose. Drug users will be alerted about dangerous test results by the drug testing systems directly and through warning campaigns. An international collaborative effort was launched to combine data of drug testing systems, called the Trans European Drug Information (TEDI) project. Drug testing systems of Spain, Switzerland, Belgium, Austria, Portugal, and the Netherlands participated in this project. This study presents results of some of the main illicit drugs encountered: cocaine, ecstasy and amphetamine and also comments on new psychoactive substances (NPS) detected between 2008 and 2013. A total of 45 859 different drug samples were analyzed by TEDI. The drug markets of the distinct European areas showed similarities, but also some interesting differences. For instance, purity of cocaine and amphetamine powders was generally low in Austria, whilst high in Spain and the Netherlands. And the market for ecstasy showed a contrast: whereas in the Netherlands and Switzerland there was predominantly a market for ecstasy tablets, in Portugal and Spain MDMA (3,4-methylenedioxymethamphetamine) crystals were much more prevalent. Also, some NPS appearing in ecstasy seemed more specific for one country than another. In general, prevalence of NPS clearly increased between 2008 and 2013. Drug testing can be used to generate a global picture of drug markets and provides information about the pharmacological contents of drugs for the population at risk. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888409 TI - Status of insecticide resistance in high-risk malaria provinces in Afghanistan. AB - BACKGROUND: Insecticide resistance seriously threatens the efficacy of vector control interventions in malaria endemic countries. In Afghanistan, the status of insecticide resistance is largely unknown while distribution of long-lasting insecticidal nets has intensified in recent years. The main objective of this study was thus to measure the level of resistance to four classes of insecticides in provinces with medium to high risk of malaria transmission. METHODS: Adult female mosquitoes were reared from larvae successively collected in the provinces of Nangarhar, Kunar, Badakhshan, Ghazni and Laghman from August to October 2014. WHO insecticide susceptibility tests were performed with DDT (4 %), malathion (5 %), bendiocarb (0.1 %), permethrin (0.75 %) and deltamethrin (0.05 %). In addition, the presence of kdr mutations was investigated in deltamethrin resistant and susceptible Anopheles stephensi mosquitoes collected in the eastern provinces of Nangarhar and Kunar. RESULTS: Analyses of mortality rates revealed emerging resistance against all four classes of insecticides in the provinces located east and south of the Hindu Kush mountain range. Resistance is observed in both An. stephensi and Anopheles culicifacies, the two dominant malaria vectors in these provinces. Anopheles superpictus in the northern province of Badakhshan shows a different pattern of susceptibility with suspected resistance observed only for deltamethrin and bendiocarb. Genotype analysis of knock down resistance (kdr) mutations at the voltage-gated channel gene from An. stephensi mosquitoes shows the presence of the known resistant alleles L1014S and L1014F. However, a significant fraction of deltamethrin-resistant mosquitoes were homozygous for the 1014L wild type allele indicating that other mechanisms must be considered to account for the observed pyrethroid resistance. CONCLUSIONS: This study confirms the importance of monitoring insecticide resistance for the development of an integrated vector management in Afghanistan. The validation of the kdr genotyping PCR assay applied to An. stephensi collected in Afghanistan paves the way for further studies into the mechanisms of insecticide resistance of malaria vectors in this region. PMID- 26888410 TI - Optimal Methods for the Management of Iatrogenic Colonoscopic Perforation. AB - BACKGROUND/AIMS: Colonoscopic perforations have been managed with exploratory laparotomy, and have resulted in some morbidity and mortality. Recently, laparoscopic surgery is commonly performed for this purpose. The aim of this study was to compare the outcomes of several management strategies for iatrogenic colonoscopic perforations. METHODS: We retrospectively reviewed the medical records of patients who had been treated for colonoscopic perforation between January 2004 and April 2013 at CHA Bundang Medical Center in Korea. RESULTS: A total of 41 patients with colonoscopic perforation were enrolled. Twenty patients underwent conservative management with a success rate of 90%. Surgical management was performed in 23 patients including two patients who were converted to surgical management after the failure of the initial conservative management. Among 14 patients who underwent surgery at 8 hours after the perforation, there was no considerable difference in adverse outcomes between the laparotomy group and the laparoscopic surgery group. The medical costs and claim rate were 1.45 and 1.87 times greater in the exploratory laparotomy group, respectively. CONCLUSIONS: Conservative management of colonoscopic perforation could be an option for patients without overt symptoms of peritonitis or with a small defect size. If surgical management is required, laparoscopic surgery may be considered as the initial procedure even with a delayed diagnosis. PMID- 26888411 TI - Brief encounters: what do primary care professionals contribute to peoples' self care support network for long-term conditions? A mixed methods study. AB - BACKGROUND: Primary care professionals are presumed to play a central role in delivering long-term condition management. However the value of their contribution relative to other sources of support in the life worlds of patients has been less acknowledged. Here we explore the value of primary care professionals in people's personal communities of support for long-term condition management. METHODS: A mixed methods survey with nested qualitative study designed to identify relationships and social network member's (SNM) contributions to the support work of managing a long-term condition conducted in 2010 in the North West of England. Through engagement with a concentric circles diagram three hundred participants identified 2544 network members who contributed to illness management. RESULTS: The results demonstrated how primary care professionals are involved relative to others in ongoing self-care management. Primary care professionals constituted 15.5 % of overall network members involved in chronic illness work. Their contribution was identified as being related to illness specific work providing less in terms of emotional work than close family members or pets and little to everyday work. The qualitative accounts suggested that primary care professionals are valued mainly for access to medication and nurses for informational and monitoring activities. Overall primary care is perceived as providing less input in terms of extended self management support than the current literature on policy and practice suggests. Thus primary care professionals can be described as providing 'minimally provided support'. This sense of a 'minimally' provided input reinforces limited expectations and value about what primary care professionals can provide in terms of support for long-term condition management. CONCLUSIONS: Primary care was perceived as having an essential but limited role in making a contribution to support work for long-term conditions. This coalesces with evidence of a restricted capacity of primary care to take on the work load of self-management support work. There is a need to prioritise exploring the means by which extended self-care support could be enhanced out-with primary care. Central to this is building a system capable of engaging network capacity to mobilise resources for self-management support from open settings and the broader community. PMID- 26888412 TI - Allium hookeri root protects oxidative stress-induced inflammatory responses and beta-cell damage in pancreas of streptozotocin-induced diabetic rats. AB - BACKGROUND: Water extract from the root of Allium hookeri (AH) shows anti inflammatory, antioxidant, and free radical scavenging effects. In this study, the ameliorating effects of AH on oxidative stress-induced inflammatory response and beta-cell damage in the pancreas of streptozotocin (STZ)-induced type 1 diabetic rats were investigated. METHODS: AH (100 mg/kg body weight/day) was orally administered every day for 2 weeks to STZ-induced diabetic rats. After the final administration of AH, biochemical parameters including glucose, insulin, reactive oxygen species levels, and protein expressions related to antioxidant defense system in the pancreas of STZ-induced diabetic rats. RESULTS: The diabetic rats showed loss of body weight and increased pancreatic weight, while the oral administration of AH attenuated body and pancreatic weight changes. Moreover, the administration of AH caused a slightly decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin levels in the diabetic rats. AH also significantly reduced the enhanced levels of reactive oxygen species, oxidative stress biomarker, in the serum and pancreas. The diabetic rats exhibited a down-regulation of the protein expression related to antioxidant defense system in the pancreas, but AH administration significantly up-regulated the expression of the heme oxygenase-1 (HO-1). Furthermore, AH treatment was reduced the overexpression of nuclear factor-kappa B (NF-kB)p65 and NF-kBp65-induced inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6. In addition, AH treatment was less pancreatic beta-cell damaged compared with those of the diabetic rats. CONCLUSION: These results provide important evidence that AH has a HO-1 activity on the oxidative stress conditions showing pancreato-protective effects against the development of inflammation in the diabetic rats. This study provides scientific evidence that AH protects the inflammatory responses by modulated NF-kBp65 signaling pathway through activation of HO-1 in the pancreas of STZ-induced diabetic rats. PMID- 26888414 TI - Physical and verbal aggressive behavior and COMT genotype: Sensitivity to the environment. AB - Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples. (c) 2016 Wiley Periodicals, Inc. PMID- 26888415 TI - Distinct neurobiological signatures of brain connectivity in depression subtypes during natural viewing of emotionally salient films. AB - BACKGROUND: Establishing an evidence-based diagnostic system informed by the biological (dys)function of the nervous system is a major priority in psychiatry. This objective, however, is often challenged by difficulties in identifying homogeneous clinical populations. Melancholia, a biological and endogenous subtype for major depressive disorder, presents a canonical test case in the search of biological nosology. METHOD: We employed a unique combination of naturalistic functional magnetic resonance imaging (fMRI) paradigms - resting state and free viewing of emotionally salient films - to search for neurobiological signatures of depression subtypes. fMRI data were acquired from 57 participants; 17 patients with melancholia, 17 patients with (non-melancholic) major depression and 23 matched healthy controls. RESULTS: Patients with melancholia showed a prominent loss of functional connectivity in hub regions [including ventral medial prefrontal cortex, anterior cingulate cortex (ACC) and superior temporal gyrus] during natural viewing, and in the posterior cingulate cortex while at rest. Of note, the default mode network showed diminished reactivity to external stimuli in melancholia, which correlated with the severity of anhedonia. Intriguingly, the subgenual ACC, a potential target for treating depression with deep brain stimulation (DBS), showed divergent changes between the two depression subtypes, with increased connectivity in the non-melancholic and decreased connectivity in the melancholic subsets. CONCLUSION: These findings reveal neurobiological changes specific to depression subtypes during ecologically valid behavioural conditions, underscoring the critical need to respect differing neurobiological processes underpinning depressive subtypes. PMID- 26888413 TI - Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data? AB - The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40-50%. We contend that the low level of maturation of penetrating cercariae (~32% for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naive mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation-attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNgamma and TNFalpha, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that "protection" in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are "successful" precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested. PMID- 26888417 TI - A randomized, double blind, placebo controlled study of spirulina supplementation on indices of mental and physical fatigue in men. AB - Spirulina may increase people's ability to resist mental and physical fatigue. This study tested that hypothesis in a randomized, double blinded, placebo controlled study in men. After 1 week, a 3 g/day dose of spirulina produced a small, but statistically significant increase in exercise output (Kcals consumed in 30 min exercise on a cross trainer machine). A mathematical based mental fatigue test showed improved performance 4 h after the first time of supplementation as well as 8 weeks later. Similarly, a subjective survey for a sense of physical and mental fatigue showed improvement within 4 h of the first supplementation as well as 8 weeks later. These results show that spirulina intake can affect fatigue in men. PMID- 26888416 TI - Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death. AB - It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 MUM H2O2-induced apoptosis of RPE cells. 200 MUM H2O2-induced generation of reactive oxygen species (ROS) and light induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-delta and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD. PMID- 26888418 TI - Amplified magnetic resonance imaging (aMRI). AB - PURPOSE: This work describes a new method called amplified MRI (aMRI), which uses Eulerian video magnification to amplify the subtle spatial variations in cardiac gated brain MRI scans and enables better visualization of brain motion. METHODS: The aMRI method takes retrospective cardiac-gated cine MRI data as input, applies a spatial decomposition, followed by temporal filtering and frequency-selective amplification of the MRI cardiac-gated frames before synthesizing a motion amplified cine data set. RESULTS: This approach reveals deformations of the brain parenchyma and displacements of arteries due to cardiac pulsatility, especially in the brainstem, cerebellum, and spinal cord. CONCLUSION: aMRI has the potential for widespread neuro- and non-neuro clinical use because it can amplify and characterize small, often barely perceptible motion and can visualize the biomechanical response of tissues using the heartbeat as an endogenous mechanical driver. Magn Reson Med 75:2245-2254, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26888420 TI - Long-term exercise maintenance in COPD via telerehabilitation: a two-year pilot study. AB - Introduction Pulmonary rehabilitation (PR) is an integral part of the management of chronic obstructive pulmonary disease (COPD). However, many patients do not access or complete PR, and long-term exercise maintenance has been difficult to achieve after PR. This study aimed to investigate feasibility, long-term exercise maintenance, clinical effects, quality of life and use of hospital resources of a telerehabilitation intervention. Methods Ten patients with COPD were offered a two-year follow-up via telerehabilitation after attending PR. The intervention consisted of home exercise, telemonitoring and self-management via a webpage combined with weekly videoconferencing sessions. Equipment included a treadmill, a pulse oximeter and a tablet. Data collected at baseline, one year and two years were six-minute walking distance (6MWD), COPD assessment test (CAT), EuroQol 5 dimensions (EQ-5D), hospitalisations and outpatient visits. Results No dropout occurred. Physical performance, lung capacity, health status and quality of life were all maintained at two years. At one year, 6MWD improved by a mean of 40 metres from baseline, CAT decreased by four points and EQ visual analogue scale (EQ VAS) improved by 15.6 points. Discussion Long-term exercise maintenance in COPD via telerehabilitation is feasible. Results are encouraging and suggest that telerehabilitation can prevent deterioration and improve physical performance, health status and quality of life. PMID- 26888419 TI - Clinical characteristics and neurodevelopmental outcomes of children with tuberculous meningitis and hydrocephalus. AB - AIM: Tuberculous meningitis (TBM) is a lethal and commonly occurring form of extra-pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus. METHOD: Demographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale - Extended Version. RESULTS: Forty four patients (median age 3y 3mo, range 3mo-13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild-moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome. INTERPRETATION: Neurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short- and long-term challenges. PMID- 26888421 TI - A systematic review on incentive-driven mobile health technology: As used in diabetes management. AB - Introduction Mobile health (mHealth) technologies have been shown to improve self management of chronic diseases, such as diabetes. However, mHealth tools, e.g. apps, often have low rates of retention, eroding their potential benefits. Using incentives is a common mechanism for engaging, empowering and retaining patients that is applied by mHealth tools. We conducted a systematic review aiming to categorize the different types of incentive mechanisms employed in mHealth tools for diabetes management, which we defined as incentive-driven technologies (IDTs). As an auxiliary aim, we also analyzed barriers to adoption of IDTs. Methods Literature published in English between January 2008-August 2014 was identified through searching leading publishers and indexing databases: IEEE, Springer, Science Direct, NCBI, ACM, Wiley and Google Scholar. Results A total of 42 articles were selected. Of these, 34 presented mHealth tools with IDT mechanisms; Education was the most common mechanism ( n = 21), followed by Reminder ( n = 11), Feedback ( n = 10), Social ( n = 8), Alert ( n = 5), Gamification ( n = 3), and Financial ( n = 2). Many of these contained more than one IDT ( n = 19). The remaining eight articles, from which we defined barriers for adoption, were review papers and a qualitative study of focus groups and interviews. Discussion While mHealth technologies have advanced over the last five years, the core IDT mechanisms have remained consistent. Instead, IDT mechanisms have evolved with the advances in technology, such as moving from manual to automatic content delivery and personalization of content. Conclusion We defined the concept of IDT to be core features designed to act as motivating mechanisms for retaining and empowering users. We then identified seven core IDT mechanisms that are used by mHealth tools for diabetes management and classified 34 articles into these categories. PMID- 26888422 TI - Copper toxicology, oxidative stress and inflammation using zebrafish as experimental model. AB - Copper is an essential micronutrient and a key catalytic cofactor in a wide range of enzymes. As a trace element, copper levels are tightly regulated and both its deficit and excess are deleterious to the organism. Under inflammatory conditions, serum copper levels are increased and trigger oxidative stress responses that activate inflammatory responses. Interestingly, copper dyshomeostasis, oxidative stress and inflammation are commonly present in several chronic diseases. Copper exposure can be easily modeled in zebrafish; a consolidated model in toxicology with increasing interest in immunity-related research. As a result of developmental, economical and genetic advantages, this freshwater teleost is uniquely suitable for chemical and genetic large-scale screenings, representing a powerful experimental tool for a whole-organism approach, mechanistic studies, disease modeling and beyond. Copper toxicological and more recently pro-inflammatory effects have been investigated in both larval and adult zebrafish with breakthrough findings. Here, we provide an overview of copper metabolism in health and disease and its effects on oxidative stress and inflammation responses in zebrafish models. Copper-induced inflammation is highlighted owing to its potential to easily mimic pro-oxidative and pro inflammatory features that combined with zebrafish genetic tractability could help further in the understanding of copper metabolism, inflammatory responses and related diseases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888424 TI - Cisplatin encapsulation within a ferritin nanocage: a high-resolution crystallographic study. AB - Cisplatin (CDDP) can be encapsulated within the central cavity of reconstituted (apo)ferritin, (A)Ft, to form a drug-loaded protein of potential great interest for targeted cancer treatments. In this study, the interactions occurring between cisplatin and native horse spleen Ft in CDDP-encapsulated AFt are investigated by high-resolution X-ray crystallography. A protein bound Pt center is unambiguously identified in AFt subunits by comparative analysis of difference Fourier electron density maps and of anomalous dispersion data. Indeed, a [Pt(NH3)2H2O](2+) fragment is found coordinated to the His132 residue located on the inner surface of the large AFt spherical cage. Remarkably, Pt binding does not alter the overall physicochemical features (shape, volume, polarity/hydrophobicity and electrostatic potential) of the outer surface of the AFt nanocage. CDDP encapsulated AFt appears to be an ideal nanocarrier for CDDP delivery to target sites, as it possesses high biocompatibility and can be internalized by receptor mediated endocytosis, thus carrying the drug to tumor tissue with higher selectivity than free CDDP. PMID- 26888423 TI - Human amniotic epithelial stem cells promote wound healing by facilitating migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways. AB - Wound healing is a highly orchestrated physiological process consisting in a complex interaction of cellular and biochemical events. Human amniotic epithelial stem cells (HAESCs) have been shown to be an attractive resource for wound healing because they are primitive stem cells. However, the exact effects of amnion-derived stem cells on the migration or proliferation of keratinocytes and their potential mechanism are not fully understood. We have found that HAESCs accelerate the migration of keratinocytes and induce a remarkable increase in the activity of phospho-ERK, phospho-JNK, and phospho-AKT, the blockade of which by their specific inhibitors significantly inhibits migration induced by HAESC conditioned medium (CM). Furthermore, the co-culture of keratinocytes with HAESCs up-regulates the expression levels of cell proliferation proteins Cyclin D1, Cyclin D3 and Mdm2. In vivo animal experiments have shown that HAESC-CM improves wound healing, whereas blockade with ERK, JNK and AKT inhibitors significantly impairs wound healing. Taken together, these results reveal, for the first time, that HAESCs promote wound healing by facilitating the migration and proliferation of keratinocytes via ERK, JNK and AKT signaling pathways and might be a potential therapy in skin wound healing. PMID- 26888425 TI - Clinical characteristics associated with non-small-cell lung cancer harboring ALK rearrangements in Chinese patients. AB - AIM: The ALK inhibitor, crizotinib, has demonstrated effectiveness in patients with non-small-cell lung cancer harboring ALK rearrangements. As few studies of the clinical characteristics of Chinese patients with ALK rearrangements have been reported, we conduct this study to gain more understanding in such area among Chinese patients. PATIENTS & METHODS: We undertook a retrospective study of 288 non-small-cell lung cancer patients admitted to our institution over a period of 4.5 years. RESULTS: Following testing, 14.9% of the patients (43/288) were found to be ALK fusion gene positive. Patient data including gender, age, smoking status, EGFR mutation status and medical imaging data were collected and analyzed. CONCLUSION: The findings suggested that patients with ALK rearrangements are more likely to be young, have EGFR wild-type, and more likely to exhibit mucus secretion, solid tumor growth, lymph node metastasis and pleural metastasis. PMID- 26888426 TI - Speciation and Structural Properties of Hydrothermal Solutions of Sodium and Potassium Sulfate Studied by Molecular Dynamics Simulations. AB - Aqueous solutions of salts at elevated pressures and temperatures play a key role in geochemical processes and in applications of supercritical water in waste and biomass treatment, for which salt management is crucial for performance. A major question in predicting salt behavior in such processes is how different salts affect the phase equilibria. Herein, molecular dynamics (MD) simulations are used to investigate molecular-scale structures of solutions of sodium and/or potassium sulfate, which show contrasting macroscopic behavior. Solutions of Na-SO4 exhibit a tendency towards forming large ionic clusters with increasing temperature, whereas solutions of K-SO4 show significantly less clustering under equivalent conditions. In mixed systems (Nax K2-x SO4 ), cluster formation is dramatically reduced with decreasing Na/(K+Na) ratio; this indicates a structure-breaking role of K. MD results allow these phenomena to be related to the characteristics of electrostatic interactions between K(+) and SO4 (2-) , compared with the analogous Na(+) -SO4 (2-) interactions. The results suggest a mechanism underlying the experimentally observed increasing solubility in ternary mixtures of solutions of Na-K-SO4 . Specifically, the propensity of sodium to associate with sulfate, versus that of potassium to break up the sodium-sulfate clusters, may affect the contrasting behavior of these salts. Thus, mutual salting-in in ternary hydrothermal solutions of Na-K-SO4 reflects the opposing, but complementary, natures of Na-SO4 versus K-SO4 interactions. The results also provide clues towards the reported liquid immiscibility in this ternary system. PMID- 26888428 TI - Deglycosylated bleomycin has the antitumor activity of bleomycin without pulmonary toxicity. AB - Bleomycin (BLM) is a potent anticancer drug used to treat different malignancies, mainly lymphomas, germ cell tumors, and melanomas. Unfortunately, BLM has major, dose-dependent, pulmonary toxicity that affects 20% of treated individuals. The most severe form of BLM-induced pulmonary toxicity is lung fibrosis. Deglyco-BLM is a molecule derived from BLM in which the sugar residue d-mannosyl-l-glucose disaccharide has been deleted. The objective of this study was to assess the anticancer activity and lung toxicity of deglyco-BLM. We compared the antitumor activity and pulmonary toxicity of intraperitoneally administrated deglyco-BLM and BLM in three rodent models. Pulmonary toxicity was examined in depth after intratracheal administration of both chemotherapeutic agents. The effect of both drugs was further studied in epithelial alveolar cells in vitro. We demonstrated in rodent cancer models, including a human Hodgkin's lymphoma xenograft and a syngeneic melanoma model, that intraperitoneal deglyco-BLM is as effective as BLM in inducing tumor regression. Whereas the antitumor effect of BLM was accompanied by a loss of body weight and the development of pulmonary toxicity, deglyco-BLM did not affect body weight and did not engender lung injury. Both molecules induced lung epithelial cell apoptosis after intratracheal administration, but deglyco-BLM lost the ability to induce caspase-1 activation and the production of ROS (reactive oxygen species), transforming growth factor-beta1, and other profibrotic and inflammatory cytokines in the lungs of mice and in vitro. Deglyco BLM should be considered for clinical testing as a less toxic alternative to BLM in cancer therapy. PMID- 26888427 TI - Ndufc2 Gene Inhibition Is Associated With Mitochondrial Dysfunction and Increased Stroke Susceptibility in an Animal Model of Complex Human Disease. AB - BACKGROUND: The genetic basis of stroke susceptibility remains to be elucidated. STR1 quantitative trait locus (STR1/QTL) was identified on rat chromosome 1 of stroke-prone spontaneously hypertensive rat (SHRSP) upon Japanese-style stroke permissive diet (JD), and it contributes to 20% of the stroke phenotype variance. METHODS AND RESULTS: Nine hundred eighty-six probe sets mapping on STR1 were selected from the Rat RAE230A array and screened through a microarray differential expression analysis in brains of SHRSP and stroke-resistant SHR (SHRSR) fed with either regular diet or JD. The gene encoding Ndufc2 (NADH dehydrogenase [ubiquinone] 1 subunit), mapping 8 Mb apart from STR1/QTL Lod score peak, was found significantly down-regulated under JD in SHRSP compared to SHRSR. Ndufc2 disruption altered complex I assembly and activity, reduced mitochondrial membrane potential and ATP levels, and increased reactive oxygen species production and inflammation both in vitro and in vivo. SHRSR carrying heterozygous Ndufc2 deletion showed renal abnormalities and stroke occurrence under JD, similarly to SHRSP. In humans, T allele variant at NDUFC2/rs11237379 was associated with significant reduction in gene expression and with increased occurrence of early-onset ischemic stroke by recessive mode of transmission (odds ratio [OR], 1.39; CI, 1.07-1.80; P=0.012). Subjects carrying TT/rs11237379 and A allele variant at NDUFC2/rs641836 had further increased risk of stroke (OR=1.56; CI, 1.14-2.13; P=0.006). CONCLUSIONS: A significant reduction of Ndufc2 expression causes complex I dysfunction and contributes to stroke susceptibility in SHRSP. Moreover, our current evidence may suggest that Ndufc2 can contribute to an increased occurrence of early-onset ischemic stroke in humans. PMID- 26888431 TI - Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model. AB - Histone deacetylase inhibitors (HDACi) are approved for treating rare cancers and are of interest as potential therapies for neurodegenerative disorders. We evaluated a triple combination formulation (TCF) comprising the pan-HDACi vorinostat, the caging agent 2-hydroxypropyl-beta-cyclodextrin (HPBCD), and polyethylene glycol (PEG) for treating a mouse model (the Npc1(nmf164) mouse) of Niemann-Pick type C (NPC) disease, a difficult-to-treat cerebellar disorder. Vorinostat alone showed activity in cultured primary cells derived from Npc1(nmf164) mice but did not improve animal survival. However, low-dose, once weekly intraperitoneal injections of the TCF containing vorinostat increased histone acetylation in the mouse brain, preserved neurites and Purkinje cells, delayed symptoms of neurodegeneration, and extended mouse life span from 4 to almost 9 months. We demonstrate that the TCF boosted the ability of HDACi to cross the blood-brain barrier and was not toxic even when used long term. Further, the TCF enabled dose reduction, which has been a major challenge in HDACi therapy. TCF simultaneously treats neurodegenerative and systemic symptoms of Niemann-Pick type C disease in a mouse model. PMID- 26888429 TI - Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo. AB - As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A gamma irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody-dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERS CoV infection and/or other emerging infectious diseases. PMID- 26888430 TI - Long noncoding RNA Chast promotes cardiac remodeling. AB - Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs in cardiac diseases is still limited. Global lncRNA expression profiling indicated that several lncRNA transcripts are deregulated during pressure overload-induced cardiac hypertrophy in mice. Using stringent selection criteria, we identified Chast (cardiac hypertrophy-associated transcript) as a potential lncRNA candidate that influences cardiomyocyte hypertrophy. Cell fractionation experiments indicated that Chast is specifically up-regulated in cardiomyocytes in vivo in transverse aortic constriction (TAC)-operated mice. In accordance, CHAST homolog in humans was significantly up-regulated in hypertrophic heart tissue from aortic stenosis patients and in human embryonic stem cell-derived cardiomyocytes upon hypertrophic stimuli. Viral-based overexpression of Chast was sufficient to induce cardiomyocyte hypertrophy in vitro and in vivo. GapmeR-mediated silencing of Chast both prevented and attenuated TAC-induced pathological cardiac remodeling with no early signs on toxicological side effects. Mechanistically, Chast negatively regulated Pleckstrin homology domain-containing protein family M member 1 (opposite strand of Chast), impeding cardiomyocyte autophagy and driving hypertrophy. These results indicate that Chast can be a potential target to prevent cardiac remodeling and highlight a general role of lncRNAs in heart diseases. PMID- 26888432 TI - Novel targets for mitochondrial medicine. AB - Mitochondria-classically viewed as the powerhouses of the cell-have taken center stage in disease pathogenesis and resolution. Mitochondrial dysfunction, which originates from primary defects within the organelle or is induced by environmental stresses, plays a critical role in human disease. Despite their central role in human health and disease, there are no approved drugs that directly target mitochondria. We present possible new druggable targets in mitochondrial biology, including protein modification, calcium ion (Ca(2+)) transport, and dynamics, as we move into a new era of mitochondrial medicine. PMID- 26888433 TI - Cost-effectiveness of the LIFE Physical Activity Intervention for Older Adults at Increased Risk for Mobility Disability. AB - BACKGROUND: Losing the ability to walk safely and independently is a major concern for many older adults. The Lifestyle Interventions and Independence for Elders study recently demonstrated that a physical activity (PA) intervention can delay the onset of major mobility disability. Our objective is to examine the resources required to deliver the PA intervention and calculate the incremental cost-effectiveness compared with a health education intervention. METHODS: The Lifestyle Interventions and Independence for Elders study enrolled 1,635 older adults at risk for mobility disability. They were recruited at eight field centers and randomly assigned to either PA or health education. The PA program consisted of 50-minute center-based exercise 2* weekly, augmented with home-based activity to achieve a goal of 150 min/wk of PA. Health education consisted of weekly workshops for 26 weeks, and monthly sessions thereafter. Analyses were conducted from a health system perspective, with a 2.6-year time horizon. RESULTS: The average cost per participant over 2.6 years was US$3,302 and US$1,001 for the PA and health education interventions, respectively. PA participants accrued 0.047 per person more Quality-Adjusted Life-Years (QALYs) than health education participants. PA interventions costs were slightly higher than other recent PA interventions. The incremental cost-effectiveness ratios were US$42,376/major mobility disability prevented and US$49,167/QALY. Sensitivity analyses indicated that results were relatively robust to varied assumptions. CONCLUSIONS: The PA intervention costs and QALYs gained are comparable to those found in other studies. The ICERS are less than many commonly recommended medical treatments. Implementing the intervention in non-research settings may reduce costs further. PMID- 26888434 TI - Sarcopenia Is Associated With Lower Skeletal Muscle Capillarization and Exercise Capacity in Older Adults. AB - BACKGROUND: Skeletal muscle capillary rarefaction limits the transcapillary transport of nutrients and oxygen to muscle and may contribute to sarcopenia and functional impairment in older adults. We tested the hypothesis that skeletal muscle capillarization and exercise capacity (VO2max) are lower in sarcopenic than in nonsarcopenic older adults and that the degree of sarcopenia is related to lower skeletal muscle capillarization. METHODS: Body composition, VO2max, and vastus lateralis capillarization were determined in 76 middle-aged and older men and women (age = 61+/-1 years, body mass index [BMI] = 30.7+/-0.5kg/m(2) [mean +/ SEM]). Participants were classified as sarcopenic if appendicular lean mass divided by BMI (ALMBMI) was less than 0.789 for men or less than 0.512 for women. RESULTS: Sarcopenic subjects (ALMBMI = 0.65+/-0.04, n = 16) had 20% lower capillary-to-fiber ratio, as well as 13% and 15% lower VO2max expressed as mL/kg/min or L/min, respectively, compared with sex-, race-, and age-matched participants without sarcopenia (ALMBMI = 0.81+/-0.05, n = 16; p < .05). In all 76 subjects, ALMBMI, thigh muscle cross-sectional area, and VO2max correlated directly with capillarization (r = .30-.37, p <= .05), after accounting for age, sex, and race. CONCLUSIONS: These findings suggest that low skeletal muscle capillarization is one factor that may contribute to sarcopenia and reduced exercise capacity in older adults by limiting diffusion of substrates, oxygen, hormones, and nutrients. Strategies to prevent the aging-related decline in skeletal muscle capillarization may help to prevent or slow the progression of sarcopenia and its associated functional declines in generally healthy older adults. PMID- 26888435 TI - Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells. AB - We previously reported that the nucleoside antibiotic tunicamycin (TN), a protein glycosylation inhibitor triggering unfolded protein response (UPR), induced neutrophil extracellular trap-osis (NETosis)-like cellular suicide and, thus, discharged genomic DNA fibers to extracellular spaces in a range of human myeloid cell lines under serum-free conditions. In this study, we further evaluated the effect of TN on human promyelocytic leukemia HL-60 cells using time-lapse microscopy. Our assay revealed a previously unappreciated early event induced by TN-exposure, in which, at 30-60 min after TN addition, the cells extruded their nuclei into the extracellular space, followed by discharge of DNA fibers to form NET-like structures. Intriguingly, neither nuclear extrusion nor DNA discharge was observed when cells were exposed to inducers of UPR, such as brefeldin A, thapsigargin, or dithiothreitol. Our findings revealed novel nuclear dynamics during TN-induced NETosis-like cellular suicide in HL-60 cells and suggested that the toxicological effect of TN on nuclear extrusion and DNA discharge was not a simple UPR. PMID- 26888438 TI - An Atomistic-Scale Study for Thermal Conductivity and Thermochemical Compatibility in (DyY)Zr2O7 Combining an Experimental Approach with Theoretical Calculation. AB - Ceramic oxides that have high-temperature capabilities can be deposited on the superalloy components in aero engines and diesel engines to advance engine efficiency and reduce fuel consumption. This paper aims to study doping effects of Dy(3+) and Y(3+)on the thermodynamic properties of ZrO2 synthesized via a sol gel route for a better control of the stoichiometry, combined with molecular dynamics (MD) simulation for the calculation of theoretical properties. The thermal conductivity is investigated by the MD simulation and Clarke's model. This can improve the understanding of the microstructure and thermodynamic properties of (DyY)Zr2O7 (DYZ) at the atomistic level. The phonon-defect scattering and phonon-phonon scattering processes are investigated via the theoretical calculation, which provides an effective way to study thermal transport properties of ionic oxides. The measured and predicted thermal conductivity of DYZ is lower than that of 4 mol % Y2O3 stabilized ZrO2 (4YSZ). It is discovered that DYZ is thermochemically compatible with Al2O3 at 1300 degrees C, whereas at 1350 degrees C DYZ reacts with Al2O3 forming a small amount of new phases. PMID- 26888437 TI - Effects of memory on the shapes of simple outbreak trees. AB - Genomic tools, including phylogenetic trees derived from sequence data, are increasingly used to understand outbreaks of infectious diseases. One challenge is to link phylogenetic trees to patterns of transmission. Particularly in bacteria that cause chronic infections, this inference is affected by variable infectious periods and infectivity over time. It is known that non-exponential infectious periods can have substantial effects on pathogens' transmission dynamics. Here we ask how this non-Markovian nature of an outbreak process affects the branching trees describing that process, with particular focus on tree shapes. We simulate Crump-Mode-Jagers branching processes and compare different patterns of infectivity over time. We find that memory (non-Markovian ness) in the process can have a pronounced effect on the shapes of the outbreak's branching pattern. However, memory also has a pronounced effect on the sizes of the trees, even when the duration of the simulation is fixed. When the sizes of the trees are constrained to a constant value, memory in our processes has little direct effect on tree shapes, but can bias inference of the birth rate from trees. We compare simulated branching trees to phylogenetic trees from an outbreak of tuberculosis in Canada, and discuss the relevance of memory to this dataset. PMID- 26888436 TI - Myosin light-chain phosphatase regulates basal actomyosin oscillations during morphogenesis. AB - Contractile actomyosin networks generate forces that drive tissue morphogenesis. Actomyosin contractility is controlled primarily by reversible phosphorylation of the myosin-II regulatory light chain through the action of myosin kinases and phosphatases. While the role of myosin light-chain kinase in regulating contractility during morphogenesis has been largely characterized, there is surprisingly little information on myosin light-chain phosphatase (MLCP) function in this context. Here, we use live imaging of Drosophila follicle cells combined with mathematical modelling to demonstrate that the MLCP subunit flapwing (flw) is a key regulator of basal myosin oscillations and cell contractions underlying egg chamber elongation. Flw expression decreases specifically on the basal side of follicle cells at the onset of contraction and flw controls the initiation and periodicity of basal actomyosin oscillations. Contrary to previous reports, basal F-actin pulsates similarly to myosin. Finally, we propose a quantitative model in which periodic basal actomyosin oscillations arise in a cell-autonomous fashion from intrinsic properties of motor assemblies. PMID- 26888439 TI - PLGA-Listeriolysin O microspheres: Opening the gate for cytosolic delivery of cancer antigens. AB - Strategies for cancer protein vaccination largely aim to activate the cellular arm of the immune system against cancer cells. This approach, however, is limited since protein vaccines mostly activate the system's humoral arm instead. One way to overcome this problem is to enhance the cross-presentation of such proteins by antigen-presenting cells, which may consequently lead to intense cellular response. Here we examined the ability of listeriolysin O (LLO) incorporated into poly-lactic-co-glycolic acid (PLGA) microspheres to modify the cytosolic delivery of low molecular weight peptides and enhance their cross-presentation. PLGA microspheres were produced in a size suitable for uptake by phagocytic cells. The peptide encapsulation and release kinetics were improved by adding NaCl to the preparation. PLGA microspheres loaded with the antigenic peptide and incorporated with LLO were readily up-taken by phagocytic cells, which exhibited an increase in the expression of peptide-MHC-CI complexes on the cell surface. Furthermore, this system enhanced the activation of a specific T hybridoma cell line, thus simulating cytotoxic T cells. These results establish, for the first time, a proof of concept for the use of PLGA microspheres incorporated with a pore forming agent and the antigen peptide of choice as a unique cancer protein vaccination delivery platform. PMID- 26888440 TI - A dual wedge microneedle for sampling of perilymph solution via round window membrane. AB - Precision medicine for inner-ear disease is hampered by the absence of a methodology to sample inner-ear fluid atraumatically. The round window membrane (RWM) is an attractive portal for accessing cochlear fluids as it heals spontaneously. In this study, we report on the development of a microneedle for perilymph sampling that minimizes the size of RWM perforation, facilitates quick aspiration, and provides precise volume control. Here, considering the mechanical anisotropy of the RWM and hydrodynamics through a microneedle, a 31G stainless steel pipe was machined into wedge-shaped design via electrical discharge machining. The sharpness of the needle was evaluated via a surface profilometer. Guinea pig RWM was penetrated in vitro, and 1 MUL of perilymph was sampled and analyzed via UV-vis spectroscopy. The prototype wedge shaped needle was successfully fabricated with the tip curvature of 4.5 MUm and the surface roughness of 3.66 MUm in root mean square. The needle created oval perforation with minor and major diameter of 143 and 344 MUm (n = 6). The sampling duration and standard deviation of aspirated volume were 3 s and 6.8 % respectively. The protein concentration was 1.74 mg/mL. The prototype needle facilitated precise perforation of RWMs and rapid aspiration of cochlear fluid with precise volume control. The needle design is promising and requires testing in human cadaveric temporal bone and further optimization to become clinically viable. PMID- 26888441 TI - Application of reference point indentation for micro-mechanical surface characterization of calcium silicate based dental materials. AB - The objective of this study was to elucidate micromechanical properties of Biodentine and two experimental calcium silicate cements (CSCs) using Reference Point Indentation (RPI). Biomechanical characteristics of the cement type and the effects of a radiopacifier, liquid components, acid etching treatment and bioactivation in simulated body fluid (SBF) were investigated by measuring the microhardness, average unloading slope (Avg US) and indentation distance increase (IDI). Biodentine had a greater microhardness than the experimental CSCs, while the Avg US and IDI values were not significantly different among investigated materials. There was a statistically significant difference in microhardness and IDI values between pure CSCs and radiopacified cements (p < 0.05). Micromechanical properties were not affected by different liquid components used. Acid-etching treatment reduced Biodentine's microhardness while cements' immersion in SBF resulted in greater microhardness and higher IDI values compared to the control group. Clearly, the physiological environment and the cements' composition affect their surface micromechanical properties. The addition of calcium chloride and CSCs' immersion in SBF are beneficial for CSCs' micromechanical performance, while the addition of radiopacifiers and acid etching treatment weaken the CSCs' surface. Application of RPI aids with the characterization of micromechanical properties of synthetic materials' surfaces. PMID- 26888442 TI - Germicide wound pad with active, in situ, electrolytically produced hypochlorous acid. AB - We describe a new wound dressing technology that can actively generate an inorganic germicide agent, in situ, within the wound pad. The technology provides real time control over the quantitative, spatial and temporal delivery of the germicide. The identity of the germicide is hypochlorous acid (HClO). The HClO is produced in a flexible wound pad, made of a composite of thin (micrometer scale) layers of various materials, with different electrochemical properties that enhance HClO production. Active control over the production of HClO is achieved by control of the pH and of the electric potential across the layers. The effectiveness of the Active HClO Pad (AHClOP) concept is demonstrated in a study on sterilization of E. coli in a deep wound contamination simulating gel. The performance of the AHClOP is compared with that of four commercial wound dressings. Results show that the AHClOP can sterilize throughout the gel, while the commercial dressings cannot. PMID- 26888444 TI - Correction to "Fossil evidence for open, ?Proteaceae-dominated heathlands and fire in ?the Late Cretaceous of Australia". PMID- 26888445 TI - Feasibility and Acute Hemodynamic Effect of Left Ventricular Septal Pacing by Transvenous Approach Through the Interventricular Septum. AB - BACKGROUND: Left ventricular septal (LVS) pacing reduces ventricular dyssynchrony and improves cardiac function relative to right ventricular apex (RVA) pacing in animals. We aimed to establish permanent placement of an LVS pacing lead in patients using a transvenous approach through the interventricular septum. METHODS AND RESULTS: Ten patients with sinus node dysfunction scheduled for dual chamber pacemaker implantation were prospectively enrolled. A custom pacing lead with extended helix was introduced via the left subclavian vein and, after positioning against the right ventricular septum (RVS) using a preshaped guiding catheter, driven through the interventricular septum to the LVS. The acute hemodynamic effect of RVA, RVS, and LVS pacing was evaluated by invasive LVdP/dtmax measurements. The lead was successfully delivered to the LVS in all patients. Procedure time and fluoroscopy time shortened with experience. QRS duration was shorter during LVS pacing (144 +/- 20 ms) than during RVA (172 +/- 33 ms; P = 0.02 versus LVS) and RVS pacing (165 +/- 17 ms; P = 0.004 versus LVS). RVA and RVS pacing reduced LVdP/dtmax compared with baseline atrial pacing (-7.1 +/- 4.1% and -6.9 +/- 4.3%, respectively), whereas LVS pacing maintained LVdP/dtmax at baseline level (1.0 +/- 4.3%; P = 0.001 versus RVA and RVS). R-wave amplitude and pacing threshold were 12.2 +/- 6.7 mV and 0.5 +/- 0.2 V at implant and remained stable during 6-month follow-up without lead-related complications. CONCLUSIONS: Permanent placement of an LVS pacing lead by transvenous approach through the interventricular septum is feasible in patients. LVS pacing preserves acute left ventricular pump function. This new pacing method could serve as an alternative and hemodynamically preferable approach for antibradycardia pacing. PMID- 26888443 TI - Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages. AB - To improve the biological properties of calcium phosphate (CaP) bone substitute, new chemical compositions are under development. In vivo such materials are subject to degradation that could lead to particles release and inflammatory reactions detrimental to the bone healing process. This study aimed at investigating the interactions between a murine macrophage cell line (RAW 264.7) and substituted hydroxyapatite particles presenting promising biological properties. Micron size particles of stoichiometric and substituted hydroxyapatites (CO3 substitution for PO4 and OH; SiO4 substitution for PO4; CO3 and SiO4 co-substitution) were obtained by aqueous precipitation followed by spray drying. Cells, incubated with four doses of particles ranging from 15 to 120 MUg/mL, revealed no significant LDH release or ROS production, indicating no apparent cytotoxicity and no oxidative stress. TNF-alpha production was independent of the chemistry of the particles; however the particles elicited a significant dose-dependent pro-inflammatory response. As micron size particles of these hydroxyapatites could be at the origin of inflammation, attention must be paid to the degradation behavior of substituted hydroxyapatite bone substitute in order to limit, in vivo, the generation of particulate debris. PMID- 26888446 TI - Early Repolarization in Athletes: A Review. PMID- 26888447 TI - Letter by Baartscheer et al Regarding Editorial, "Matter of Fat: Are Lipids Antiarrhythmic?". PMID- 26888448 TI - The relationship between three eGFR formulas and hospitalization for heart failure in 54 486 individuals with type 2 diabetes. AB - OBJECTIVE: This study aims to study the association between renal function and hospitalization for heart failure (HF) in individuals with type 2 diabetes. METHODS: Renal function was determined according to three formulas used to estimate glomerular filtration rate (eGFR): Cockcroft-Gault, modified diet in renal disease (MDRD) and chronic kidney disease epidemiology (CKD-EPI). Proportional hazards regression models adjusted for age, sex, HbA1c , blood pressure, smoking and cardiovascular comorbidities were constructed for each eGFR formula to estimate risk of hospitalization for heart failure. Systematic pairwise likelihood ratio tests of nested models were used to compare the predictive power of each eGFR formula. RESULTS: In 54 486 patients, evaluated over a median follow-up of 7.0 years, a total of 5936 (10.9%) developed heart failure, with an excess risk in all eGFR categories below 60 mL/min/1.73 m2 (reference: eGFR >90 mL/min/1.73 m2 ). Hazard ratios ranged from 1.25 to 1.35 for eGFR 45-60 mL/min/1.73 m2 , 1.62 to 1.66 for eGFR 30-45 mL/min/1.73 m2 and 2.18 to 2.52 for eGFR <30 mL/min/1.73 m2 in the three eGFR formulas. In pairwise comparisons, the model with the MDRD variable added significantly more information than the Cockcroft-Gault variable. For the model with the CKD-EPI variable, no clear differences in predictive power for HF hospitalization existed in relation to the other eGFR formulas. CONCLUSION: Patients with type 2 diabetes, with eGFR 45 to 60 mL/min/1.73 m2 , have approximately 25-35% increased risk of hospitalization for HF, increasing with lower eGFR, to 2-2.5 times in those with eGFR <30 mL/min/1.73 m2 . The MDRD formula for calculating eGFR is more predictive of hospitalization for heart failure than the Cockcroft-Gault formula. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888449 TI - Parameterizing the Transport Pathways for Cell Invasion in Complex Scaffold Architectures. AB - Interconnecting pathways through porous tissue engineering scaffolds play a vital role in determining nutrient supply, cell invasion, and tissue ingrowth. However, the global use of the term "interconnectivity" often fails to describe the transport characteristics of these pathways, giving no clear indication of their potential to support tissue synthesis. This article uses new experimental data to provide a critical analysis of reported methods for the description of scaffold transport pathways, ranging from qualitative image analysis to thorough structural parameterization using X-ray Micro-Computed Tomography. In the collagen scaffolds tested in this study, it was found that the proportion of pore space perceived to be accessible dramatically changed depending on the chosen method of analysis. Measurements of % interconnectivity as defined in this manner varied as a function of direction and connection size, and also showed a dependence on measurement length scale. As an alternative, a method for transport pathway parameterization was investigated, using percolation theory to calculate the diameter of the largest sphere that can travel to infinite distance through a scaffold in a specified direction. As proof of principle, this approach was used to investigate the invasion behavior of primary fibroblasts in response to independent changes in pore wall alignment and pore space accessibility, parameterized using the percolation diameter. The result was that both properties played a distinct role in determining fibroblast invasion efficiency. This example therefore demonstrates the potential of the percolation diameter as a method of transport pathway parameterization, to provide key structural criteria for application-based scaffold design. PMID- 26888451 TI - A Representative Survey of Knowledge, Use, Perceived Benefits, Barriers, and Risks of Select Herbal Drugs Among Female Students in Gorgan City (Northeast Iran). AB - We conducted a representative survey among young women to determine knowledge, use, and perceptions on barriers, benefits, and risks related to selected herbal drugs ( Crocus sativus, Borago officinalis, Citrus aurantium, Thymus vulgaris, Matricaria chamomilla, Lavandula angustifolia, Valeriana officinalis, Hypericum perforatum, and Panax ginseng) in Gorgan by using an internally validated questionnaire. There were 344 participants (mean age 16.3 years; 16.2% in science course). Saffron had most reported knowledge (n = 265, 77.0%) and ever use (n = 324, 94.1%). The average number of source of knowledge was 2.5; parents (n = 224, 65.1%) were the single most frequent source. Media (combined magazine, the Internet, TV, radio) was the source of knowledge for 283 (82.2%) participants. Actual use was "harmful" for the majority (n = 182, 52.9%; no idea n = 83, 24.1%). Parents and media provided knowledge on herbal drugs for most, supporting unsurprisingly high perceived knowledge but harmful actual experience. Programs to educate people are needed to not take herbal drugs lightly. PMID- 26888450 TI - Chronic consumption of a western diet induces robust glial activation in aging mice and in a mouse model of Alzheimer's disease. AB - Studies have assessed individual components of a western diet, but no study has assessed the long-term, cumulative effects of a western diet on aging and Alzheimer's disease (AD). Therefore, we have formulated the first western-style diet that mimics the fat, carbohydrate, protein, vitamin and mineral levels of western diets. This diet was fed to aging C57BL/6J (B6) mice to identify phenotypes that may increase susceptibility to AD, and to APP/PS1 mice, a mouse model of AD, to determine the effects of the diet in AD. Astrocytosis and microglia/monocyte activation were dramatically increased in response to diet and was further increased in APP/PS1 mice fed the western diet. This increase in glial responses was associated with increased plaque burden in the hippocampus. Interestingly, given recent studies highlighting the importance of TREM2 in microglia/monocytes in AD susceptibility and progression, B6 and APP/PS1 mice fed the western diet showed significant increases TREM2+ microglia/monocytes. Therefore, an increase in TREM2+ microglia/monocytes may underlie the increased risk from a western diet to age-related neurodegenerative diseases such as Alzheimer's disease. This study lays the foundation to fully investigate the impact of a western diet on glial responses in aging and Alzheimer's disease. PMID- 26888454 TI - Segmented Sleep in Preindustrial Societies. PMID- 26888452 TI - Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype. AB - STUDY OBJECTIVES: We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). METHODS: Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). RESULTS: Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. CONCLUSIONS: IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. COMMENTARY: A commentary on this article appears in this issue on page 723. PMID- 26888453 TI - Association between Obstructive Sleep Apnea and Left Ventricular Structure by Age and Gender: the Multi-Ethnic Study of Atherosclerosis. AB - STUDY OBJECTIVES: The presence and severity of obstructive sleep apnea (OSA) are associated with impaired left ventricular (LV) structure and function. Our goal was to quantify the associations between LV systolic function and mass with severity of OSA in an ethnically diverse cohort, assessing variations by age and sex. METHODS: We conducted a cross-sectional analysis of data from 1,412 racially/ethnically diverse participants across 6 US communities from the Multi Ethnic Study of Atherosclerosis who underwent both overnight polysomnography and cardiac magnetic resonance imaging from 2010-2012. We evaluated the association between the obstructive apnea-hypopnea index (AHI) by clinical category (< 5, 5 15, 15-30, 30-50, > 50) and secondary measures of sleep apnea with the outcomes left ventricular (LV) mass adjusted for height, LV mass/volume ratio, and LV ejection fraction. RESULTS: After adjusting for potential confounders and mediators, LV mass was significantly increased with increasing AHI category for subjects age 65 y or younger (beta = 1.84 +/- 0.47 g/m, P = 0.0001). The association between the AHI and LV mass appeared stronger in whites and Chinese compared to blacks and Hispanics, although interaction terms were not statistically significant. Additionally, while both LV mass and LV mass/volume ratio were significantly associated with hypoxia, ejection fraction was not associated with any OSA severity index. Comparable associations were observed in men and women. CONCLUSIONS: Independent of confounders, higher levels of AHI are significantly associated with increased LV mass in both men and women younger than 65 y from a community-based cohort. PMID- 26888456 TI - Alkyne Difunctionalization by Dual Gold/Photoredox Catalysis. AB - Highly selective tandem nucleophilic addition/cross-coupling reactions of alkynes have been developed using visible-light-promoted dual gold/photoredox catalysis. The simultaneous oxidation of Au(I) and coordination of the coupling partner by photo-generated aryl radicals, and the use of catalytically inactive gold precatalysts allows for high levels of selectivity for the cross-coupled products without competing hydrofunctionalization or homocoupling. As demonstrated in representative arylative Meyer-Schuster and hydration reactions, this work expands the scope of dual gold/photoredox catalysis to the largest class of substrates for gold catalysts and benefits from the mild and environmentally attractive nature of visible-light activation. PMID- 26888455 TI - How Much Day-To-Day Variability in Sleep Timing Is Unhealthy? PMID- 26888457 TI - Safety of third-generation artificial turf in male elite professional soccer players in Italian major league. AB - Our hypothesis is that there are no difference in the injury incidence on artificial turf and natural grass. During the 2011/2012 season, we recorded injuries which occurred to two Italian stadiums equipped with third-generation artificial turf during 36 games (391 players). Data were compared with the injuries which occurred in the same season in two stadiums equipped with natural grass (372 players). We recorded 43 injuries during the playing time (16.7 per 1000 h). About 23 (18.1 per 1000 h) injuries occurred on artificial turf, while 20 (15.2 per 1000 h) on the natural grass with no statistical differences P > 0.05. We recorded 10 (7.87 per 1000 h) contact and 13 (10.23 per 1000 h) non contact injuries on artificial turf, while 5 (3.8 per 1000 h) contact and 15 (11.4 per 1000 h) non-contact injuries on natural grass P > 0.05. The overall relative risk was 1.15; 95% CI: 0.64-2.07). Our study demonstrates a substantial equivalence in injury risk on natural grass and artificial turf in elite professional soccer athletes during official matches. PMID- 26888458 TI - Kinetics of photochemical reactions of biphotochromic compounds based on spironaphthopyran and enamine--conjugation effect. AB - A novel biphotochromic compound (BPC) with two photochromic fragments, namely spironaphthopyran and hydroxyazomethine, was synthesized and studied by nanosecond laser flash photolysis using the excitation wavelengths of 337, 430, 470 and 500 nm in methanol and toluene. The photoexcitation of BPC results in the formation of at least two colored transients. The first one is the merocyanine form B (the maximum in the absorption spectrum is near 600 nm and the lifetime is 0.1 and 0.05 s in methanol and toluene, respectively) due to the spiro-bond break followed by isomerization. The second one is the trans-keto form A(Kt) (the maximum in the absorption spectra is near 480 nm and the lifetime is 0.1 and 5 ms in methanol and toluene, respectively) as a result of cis-enol or cis-keto tautomer transformations. The relative yields of B and A(Kt) depends essentially on the wavelength of excitation. The form A(Kt) is the key transient formed under excitation with the visible light, whereas its yield under excitation with UV light is comparable with that of B. The specific solvation by methanol molecules favors the spirocycle opening even under visible light excitation. The results obtained for novel BPC were compared with those for other BPC where the same fragments are combined in such a way that the form B is the major one under excitation with UV light whereas it virtually is not observed under visible light excitation. The difference in both BPC is discussed in terms of conjugation (pi coupling) between photochromic fragments. PMID- 26888459 TI - Mobile medical technology: the revolution in medicine is in your smartphone. PMID- 26888460 TI - Open heart surgery for a stuck rotablator. PMID- 26888461 TI - Can radiological characteristics of preoperative cerebral lesions predict postoperative intracranial haemorrhage in endocarditis patients? AB - OBJECTIVES: Infective endocarditis (IE) is associated with high mortality (20 40%) and neurological complications (20-50%). Postoperative intracranial haemorrhage (ICH) is a feared complication especially in patients with preoperative cerebral infarcts. The aim of this study was to determine the radiological characteristics of cerebral lesions that could predict the occurrence of postoperative ICH in IE patients. METHODS: We retrospectively reviewed all charts, brain imaging and follow-up data from patients operated for left-sided endocarditis between January 2007 and April 2013. RESULTS: A total of 308 patients (age 62.0 +/- 13.9) underwent surgery for IE. Preoperative cerebrovascular complications were present in 122 patients (39.6%), representing stroke in 87, silent cerebral infarctions in 31 patients and transient ischaemic attacks in 4 patients. Among 118 patients with cerebral lesions, the aetiological classification of the lesions was ischaemic in 63.6%, ischaemic with haemorrhagic transformation (HT) in 17.8%, ischaemic with concomitant microbleeds in 16.1% and intracerebral bleeding in 2.5%. Postoperative ICH occurred in 17 patients and its incidence was slightly higher in patients with preoperative cerebral infarcts compared with those without preoperative cerebral infarcts [7.6 vs 4.2%, respectively, odds ratio (OR) 1.88, 95% confidence interval (CI) 0.70-5.02, P = 0.21]. However, the difference was not statistically significant. Similarly, the incidence of postoperative ICH was higher in cases of HT of ischaemic infarcts than in cases of ischaemic infarcts not complicated with HT (19.0 vs 5.3%). However, the difference was not statistically significant (P = 0.24). The radiological pattern of preoperative cerebral lesions was single in 35.6% and multiple in 60.0% of cases. Multiple cerebral lesions were associated with a non significantly lower incidence of postoperative ICH than single lesions (5.6 vs 11.9%, respectively, OR: 0.44, CI: 0.11-1.73, P = 0.29). CONCLUSIONS: The results suggest that the incidence of postoperative ICH in IE patients was slightly higher in the presence of preoperative cerebral infarcts. In addition, preoperative cerebral ischaemic infarcts complicated with HT tended to have a higher incidence of postoperative ICH than those not complicated with HT. However, the difference was not statistically significant. Multiple preoperative cerebral infarcts were not associated with higher incidence of postoperative ICH compared with single cerebral infarcts. PMID- 26888462 TI - Meta-analysis of concomitant mitral valve repair and coronary artery bypass surgery versus isolated coronary artery bypass surgery in patients with moderate ischaemic mitral regurgitation. AB - Ischaemic mitral regurgitation (IMR) is a complication of coronary artery disease with normal chordal and leaflet morphology. Controversy surrounds the issue of appropriate surgical management of moderate IMR. With the present meta-analysis, we aimed to determine whether the addition of mitral valve (MV) repair to coronary artery bypass grafting (CABG) improved clinical outcome over CABG alone in patients with moderate IMR. Databases were searched for studies reporting on clinical outcomes after CABG and MV repair or CABG alone for moderate IMR. Clinical end-points were operative mortality, survival, New York Heart Association (NYHA) class >=2 and MR grade >=2 at last follow-up. A total of five observational and four randomized controlled trials (RCTs) were identified. The mean follow-up was 2.7 years. An analysis of all studies revealed increased operative risk in the concomitant CABG and MV repair group {risk ratio [RR] 2.02 [95% confidence interval (CI) 1.15, 3.56], P = 0.01, I(2) = 0%}. However, an analysis of RCTs only showed that the operative risk was equivalent [RR 1.05 (95% CI 0.34, 3.30), P = 0.93, I(2) = 0%]. Pooled hazard ratio (HR) on survival did not favour either procedure [all studies: HR 1.08 (95% CI 0.77, 1.50), P = 0.66, I(2) = 0%; RCTs only: HR 0.89 (95% CI 0.47, 1.70), P = 0.73, I(2) = 0%]. The incidence of exercise intolerance quantified as NYHA class >=2 was similar between groups (all studies: RR 0.72 (95% CI 0.42, 1.24), P = 0.24, I(2) = 77%; RCTs only: RR 0.61 (95% CI 0.24, 1.55), P = 0.30, I(2) = 83%]. Risk of residual MR grade >=2 was higher in the CABG only group [all studies: RR 0.30 (95% CI 0.16, 0.60), P < 0.001, I(2) = 83%; RCTs only: RR 0.20 (95% CI 0.04, 0.90), P = 0.04, I(2) = 72%]. There is neither increased operative mortality nor survival benefit associated with concomitant CABG and MV repair for IMR of moderate degree over CABG alone. Further studies with long-term follow-up data and sub-group analyses of current data are needed to define a subset of patients whose survival and functional status may improve with the concomitant MV repair. PMID- 26888463 TI - Improving outcomes: case-matched comparison of novel second-generation versus first-generation self-expandable transcatheter heart valves. AB - OBJECTIVES: The published literature has extensively documented clinical benefit derived from transcatheter aortic valve implantation (TAVI) in high-risk patients using self-expanding current-generation transfemoral (TF) transcatheter heart valves (THVs). However, it has also demonstrated apparent shortcomings such as paravalvular leakage (PVL) or need for permanent pacemaker (PM) implantation. We here present a case-matched analysis of acute 30-day outcomes using a novel nitinol-based THV (Symetis Acurate Neo TFTM), which may overcome some limitations of currently used devices. METHODS: From 2012 to 2015, 69 consecutive patients (study group, 65.2% female, 81.4 +/- 6.1 years, logEuroSCORE I 19.9 +/- 14.2%) received TF-TAVI using the novel Symetis Acurate Neo TFTM THV. A control group of patients after TF-TAVI with the CoreValveTM THV was retrieved from our database (control group) and matched to the study group utilizing 16 parameters. Data were retrospectively analysed according to updated Valve Academic Research Consortium (VARC-2) definitions. The 30-day follow-up was completed in all cases. RESULTS: Apart from gender (65.2 vs 44.9% females, P = 0.023), matching was successful with parameters showing no significant differences. The device success rate was 95.6% (66/69) and 89.9% (62/69) in the study and control groups, respectively (P = 0.20). The all-cause 30-day mortality rate was 5.8% (4/69) vs 10.14% (7/69) (P = 0.36), and disabling stroke was observed in 2.9% (2/69) vs 5.8% (4/69) (P = 0.41), respectively. Resultant transvalvular maximum/mean gradient and effective orifice area (EOA) were 13.8 +/- 5.5 vs 18.1 +/- 8.1 mmHg (P = 0.001)/7.0 +/- 2.8 vs 8.8 +/- 4.0 mmHg (P = 0.006) and 1.9 +/- 0.3 vs 1.8 +/- 0.2 cm(2) (P = 0.015), respectively. PVL >=grade II was observed in 2.9% (2/69) and 15.94% (11/69) (P = 0.013) of patients and the rate of PM implantation was 8.7% (6/69) vs 44.9% (31/69) (P < 0.001), respectively. DISCUSSION: TF-TAVI was feasible and safe using this new type of nitinol-based THV. Superiority to the current generation of self-expanding THVs was achieved regarding post-interventional pressure gradients and EOA, severity of residual PVL and rate of PM implantation. Results set a promising quality standard for TF-TAVI with a self-expanding THV, but will have to be confirmed in a larger patient cohorts for further clinical evaluation. PMID- 26888464 TI - New miniplate for osteosynthesis of mandibular angle fractures designed to improve formation of new bone. AB - The purpose of this article is to present the study of a new miniplate designed to keep the maximum strains developed in the cortical bone near the fracture line during accidental biting to values below the threshold causing bone resorption. Designed to offer maximum fracture stability with minimal implanted volume and patient intrusion, the design uses a novel approach to account for the effects of the distance from the fracture line to the nearest screws. Its geometry minimizes the peak forces that can develop during most cases of mandible biomechanical loadings. A three-dimensional (3D) osteosynthesis finite element model for a human mandible confirmed the operational effectiveness of the miniplate. It also provided numerical estimates for the strains and screw forces in the cortical surface during incisor bites with clinically relevant forces of 200 N. Two prototypes, 0.6 mm and 0.8 mm in thickness, were repeatedly tested on fractured sheep mandibles, fixed in a purpose-built jig, to loads up to 150% of the maximum forces developed by human patients. The tests indicated good fracture stability, and the proof tests carried for each of the two prototypes terminated at more than 350 N due to failure of the loading cable and respectively, secondary mandible fractures occurring away from the miniplate. PMID- 26888465 TI - The ideal male jaw angle--An Internet survey. AB - BACKGROUND: The ideal male jaw angle has not been established. With the advent of additive manufacturing, precise customized shaping is a reality. This study aimed to define the ideal masculine mandibular angle as an aid for 3-dimensional (3D) design. METHODS: An Internet survey was conducted using black/white photographs of celebrities and non-celebrities. Preferences regarding gonial angle (profile and frontal views), intergonial width and vertical jaw angle position (face frontal view), and angle curvature and definition in oblique views were obtained using simplified, unbalanced Likert scales. Constructs were defined for planning 3D implant designs. RESULTS: The preferred jaw angle had these characteristics: 130 degrees in face profile view, intergonial width similar to facial width, vertical position in frontal view at the oral commissure or at least not below the lower lip, jawline slope in the face frontal view nearly parallel to (with a maximum 15 degrees downward deviation from) a line extending from the lateral canthus to the alare, ascending ramus slope 65 degrees -75 degrees to the Frankfort horizontal, and curvature in the oblique view visible from earlobe to chin and not pointy. CONCLUSIONS: Photogrammetric analysis of panel preferences lead to constructs with values useful for the design of 3D printed jaw angles. PMID- 26888466 TI - Assessing Cell-to-Cell DNA Methylation Variability on Individual Long Reads. AB - Understanding cell-to-cell variability in cytosine methylation is essential for understanding cellular perturbation and its molecular machinery. However, conventional methylation studies have focused on the differences in the average levels between cell types while overlooking methylation heterogeneity within cell types. Little information has been uncovered using recent single-cell methods because of either technical limitations or the great labor required to process many single cells. Here, we report the highly efficient detection of cell-to-cell DNA methylation variability in liver tissue, based on comparing the methylation status of adjacent CpG sites on long sequencing reads. This method provides abundant methylation linkage information and enables genome-wide estimation of cell-to-cell variability. We observed repressed methylation variability in hypomethylated regions compared with the variability in hypomethylated regions across the genome, which we confirmed using public human sperm data. A gradual change in methylation status at the boundaries of hypomethylated regions was observed for the first time. This approach allows the concise, comprehensive assessment of cell-to-cell DNA methylation variability. PMID- 26888468 TI - Roles and regulation of the matrix metalloproteinase system in parturition. AB - Significant tissue destruction, repair, and remodeling are involved in parturition, which involves fetal membrane rupture, cervical ripening, and uterine contraction and its subsequent involution. Extracellular matrix degradation and remodeling by proteolytic enzymes, such as matrix metalloproteinases (MMPs), are required for the final steps of parturition. MMPs participate in physiological degradation and remodeling through their proteolytic activities on specific substrates, and are balanced by the action of their inhibitors. Disruption to this balance can result in pathological stress that ends with preterm or post-term birth or pre-eclampsia. In this review, we examine the roles and regulation of the MMP system in physiological and pathological labor, and propose a model that illustrates the mechanisms by which the MMP system contributes to these processes. PMID- 26888467 TI - Effect of whole-body vibration on reduction of bone loss and fall prevention in postmenopausal women: a meta-analysis and systematic review. AB - BACKGROUND: To examine whole-body vibration (WBV) effect on bone mineral density (BMD) and fall prevention in postmenopausal women, we performed a meta-analysis and systematic review of prospective randomized controlled trials (RCTs) comparing change in BMD of the femoral neck and lumbar spine and related factors of falls between WBV group and control group. METHODS: EMBASE, PubMed, Cochrane Central Register of Controlled Trials, ISI Web of Science, and China National Knowledge Infrastructure (CNKI) were searched up to April 2015; search strategy was used as follows: (vibration) AND (osteoporo* OR muscle* OR bone mineral density OR BMD). All prospective randomized controlled trials comparing related factors of falls and BMD change in the femoral neck and lumbar spine between WBV group and control group were retrieved. RESULTS: Eight of 3599 studies with 1014 patients were included, 477 in the WBV group, and 537 in the control group. We found that there was no significant difference in all magnitude groups of the femoral neck (N = 936, WMD: 0.00 (-0.00, 0.01); p = 0.18). A statistical significance showed in the all magnitude groups (N = 1014, WMD: 0.01 (0.00, 0.01); p = 0.01) and low-magnitude group (N = 838, WMD: 0.01 (0.00, 0.01); p = 0.007) of the lumbar spine. No significant difference was found in high-magnitude group of the lumbar spine (N = 176, WMD: 0.00 (-0.01, 0.02); p = 0.47), low magnitude group (N = 838, WMD: 0.00 (-0.00, 0.00); p = 0.92) and high-magnitude group (N = 98, WMD: 0.02 (-0.00, 0.05); p = 0.06) of the femoral neck. All the studies provided data of related factors of falls such as strength of the lower limb, balance, and fall rate reported effectiveness of WBV therapy. In addition, no complication was reported. CONCLUSIONS: Low-magnitude whole-body vibration therapy can provide a significant improvement in reducing bone loss in the lumbar spine in postmenopausal women. Moreover, whole-body vibration can be used as an intervention for fall prevention. PMID- 26888469 TI - Virtual screening of the inhibitors targeting at the viral protein 40 of Ebola virus. AB - BACKGROUND: The Ebola virus is highly pathogenic and destructive to humans and other primates. The Ebola virus encodes viral protein 40 (VP40), which is highly expressed and regulates the assembly and release of viral particles in the host cell. Because VP40 plays a prominent role in the life cycle of the Ebola virus, it is considered as a key target for antiviral treatment. However, there is currently no FDA-approved drug for treating Ebola virus infection, resulting in an urgent need to develop effective antiviral inhibitors that display good safety profiles in a short duration. METHODS: This study aimed to screen the effective lead candidate against Ebola infection. First, the lead molecules were filtered based on the docking score. Second, Lipinski rule of five and the other drug likeliness properties are predicted to assess the safety profile of the lead candidates. Finally, molecular dynamics simulations was performed to validate the lead compound. RESULTS: Our results revealed that emodin-8-beta-D-glucoside from the Traditional Chinese Medicine Database (TCMD) represents an active lead candidate that targets the Ebola virus by inhibiting the activity of VP40, and displays good pharmacokinetic properties. CONCLUSION: This report will considerably assist in the development of the competitive and robust antiviral agents against Ebola infection. PMID- 26888470 TI - Hedonic sensitivity to low-dose ketamine is modulated by gonadal hormones in a sex-dependent manner. AB - We recently reported a greater sensitivity of female rats to rapid antidepressant like effects of ketamine compared to male rats, and that ovarian-derived estradiol (E2) and progesterone (P4) are essential for this response. However, to what extent testosterone may also contribute, and whether duration of response to ketamine is modulated in a sex- and hormone-dependent manner remains unclear. To explore this, we systematically investigated the influence of testosterone, estradiol and progesterone on initiation and maintenance of hedonic response to low-dose ketamine (2.5 mg/kg) in intact and gonadectomized male and female rats. Ketamine induced a sustained increase in sucrose preference of female, but not male, rats in an E2P4-dependent manner. Whereas testosterone failed to alter male treatment response, concurrent administration of P4 alone in intact males enhanced hedonic response low-dose ketamine. Treatment responsiveness in female rats only was associated with greater hippocampal BDNF levels, but not activation of key downstream signaling effectors. We provide novel evidence supporting activational roles for ovarian-, but not testicular-, derived hormones in mediating hedonic sensitivity to low-dose ketamine in female and male rats, respectively. Organizational differences may, in part, account for the persistence of sex differences following gonadectomy and selective involvement of BDNF in treatment response. PMID- 26888472 TI - Mental health problems in people living with HIV: changes in the last two decades: the London experience 1990-2014. AB - Mental health problems continue to be a significant comorbidity for people with HIV infection, even in the era of effective antiretroviral therapy. Here, we report on the changes in the mental health diagnoses based on clinical case reports amongst people with HIV referred to a specialist psychological medicine department over a 24-year period, which include the relative increase in depressive and anxiety disorders, often of a chronic nature, together with a decline in acute mental health syndromes, mania, and organic brain disorders. In addition, new challenges, like the presence of HIV and Hepatitis C co-infection, and the new problems created by recreational drugs, confirm the need for mental health services to be closely involved with the general medical services. A substantial proportion of people with HIV referred to specialist services suffer complex difficulties, which often require the collaboration of both psychiatrists and psychologists to deal effectively with their difficulties. PMID- 26888471 TI - Energy drink consumption, health complaints and late bedtime among young adolescents. AB - OBJECTIVES: Energy drinks contain large amounts of caffeine. Their effects on adolescent well-being are poorly known. We examined the relationship of energy drink consumption with health complaints and late bedtime among 13-year-olds. METHODS: A classroom survey was conducted on all 7th graders in the Helsinki metropolitan region, Finland (73 % responded; n = 9446). Logistic regression analysis and structural equation modeling (SEM) were used. RESULTS: The prevalence of health complaints increased as energy drink consumption increased from non-consumers to several times/day. Late bedtime (>=11 PM) increased correspondingly. Those consuming energy drinks several times/day exhibited increased odds of experiencing daily health complaints compared with non consumers: headache OR (adjusted) = 4.6 (2.8-7.7), sleeping problems OR = 3.6 (2.2-5.8), irritation OR = 4.1 (2.7-6.1), tiredness/fatigue OR = 3.7 (2.4-5.7), and late bedtime OR = 7.8 (5.7-10.9). In SEM, energy drink consumption had a direct effect on health complaints and late bedtime and an indirect effect on health complaints via late bedtime. CONCLUSIONS: Energy drinks, late bedtime, and health complaints form a behavior pattern that is worth considering in schools, home and clinical settings when adolescents complain about headaches, problems with sleeping and corresponding symptoms. PMID- 26888473 TI - Stepwise increase of hypermetropic correction using contact lenses in intermittent partially accommodative esotropia. AB - BACKGROUND: The aim was to present a series of patients with intermittent partially accommodative esotropia (pAcc-ET) in evaluating the effect of over-plus correcting the hypermetropia relative to the non-cycloplegic refraction using contact lenses. METHODS: Twenty-three patients (23.8 +/- 8.9 years) with intermittent pAcc-ET were fitted with soft daily single-vision contact lenses and the hypermetropia was over-plus corrected relative to the original subjective non cycloplegic refraction, reducing distance visual acuity to 0.8 (decimal acuity). Hypermetropia correction was increased at follow-ups (every second week) until visual acuity stabilised or symptoms ceased. The contact lenses were worn for the entire study period. RESULTS: After eight weeks of treatment (two to four follow ups) the intermittent esotropia stabilised into esophoria and the magnitude of the deviation at distance was reduced in 70 per cent (16/23) of patients and at near in 91 per cent (21/23) of patients. As a result calculated accommodative convergence and the level of accommodation (stimulus AC/A ratio) was reduced in 83 per cent (19/23) of patients but still classified as high (less than 5:1). CONCLUSIONS: Compared to correction based on original non-cycloplegic subjective refraction, increasing correction of hypermetropia with contact lenses in partially accommodative esotropia reduced the magnitude of the eso-deviation at distance and near. In addition to reducing accommodative demand and stimulus AC/A with increasing hyperopic correction, contact lenses may provide additional benefit given the increased hyperopic correction and the decreased stimulus for accommodation required at the corneal plane. PMID- 26888474 TI - A 10-year retrospective analysis of hospital admissions and length of stay among a cohort of homeless adults in Vancouver, Canada. AB - BACKGROUND: Homelessness is associated with a very high prevalence of substance use and mental disorders and elevated levels of acute health service use. Among the homeless, little is known regarding the relative impact of specific mental disorders on healthcare utilization. The aim of the present study was to examine the association between different categories of diagnosed mental disorders with hospital admission and length of stay (LOS) in a cohort of homeless adults in Vancouver, Canada. METHODS: Participants were recruited as part of an experimental trial in which participants met criteria for both homelessness and mental illness. Administrative data were obtained (with separate consent) including comprehensive records of acute hospitalizations during the 10 years prior to recruitment and while participants where experiencing homelessness. Generalized Estimating Equations were used to estimate the associations between outcome variables (acute hospital admissions and LOS) and predictor variables (specific disorders). RESULTS: Among the eligible sample (n = 433) 80 % were hospitalized, with an average of 6.0 hospital admissions and 71.4 days per person during the 10-year observation period. Of a combined total 2601 admissions to hospital, 1982 were psychiatric and 619 were non-psychiatric. Significant (p <0.001) independent predictors of hospital admission and LOS included a diagnosis of schizophrenia or bipolar disorder, as well as high (>=32 service contacts) non psychiatric medical service use in the community. CONCLUSIONS: Our results demonstrate that specific mental disorders alongside high non-psychiatric service use were significantly associated with hospital admission and LOS. These findings suggest the importance of screening within the homeless population to identify individuals who may be at risk for acute illness and the implementation of services to promote recovery and prevent repeated hospitalization. TRIAL REGISTRATION: ISRCTN57595077 ; ISRCTN66721740. PMID- 26888475 TI - Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation. AB - Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients. PMID- 26888476 TI - Renal Function Profile in White Kidney Donors: The First 4 Decades. AB - Previous studies reported the risk of ESRD after kidney donation, but not the renal outcomes that precede ESRD. Here, we estimated the risk of proteinuria, reduced GFR, and ESRD in 3956 white kidney donors, assessed the contribution of postdonation hypertension and diabetes to these outcomes, and developed a risk calculator. After a mean+/-SD follow-up of 16.6+/-11.9 years, 215 (6.1%) donors developed proteinuria. Men had a higher risk of proteinuria (hazard ratio [HR], 1.56; 95% confidence interval [95% CI], 1.18 to 2.05; P<0.001) as did those with higher body mass index (HR, 1.10; 95% CI, 1.06 to 1.13; P<0.001). In all, 1410 (36%) donors reached an eGFR<60 ml/min per 1.73 m(2), and 112 (2.8%) donors had either an eGFR<30 ml/min per 1.73 m(2) or ESRD (28 donors developed ESRD). An eGFR<30 ml/min per 1.73 m(2) or ESRD associated with older age (HR, 1.07; 95% CI, 1.05 to 1.09; P<0.001), higher body mass index (HR, 1.08; 95% CI, 1.04 to 1.13; P<0.001), and higher systolic BP (HR, 1.02; 95% CI, 1.00 to 1.04; P=0.01) at donation. Postdonation diabetes and hypertension associated with a fourfold higher risk of proteinuria and a >2-fold higher risk of ESRD. Models predicting proteinuria and reduced eGFR performed well (C-index 0.77-1.00). In conclusion, severe reduction in GFR and ESRD after kidney donation were uncommon and were highly associated with postdonation diabetes and hypertension. Furthermore, information available before donation may predict long-term renal outcomes in white living kidney donors. PMID- 26888477 TI - The interpreter as co-interviewer: the role of the interpreter during interviews in cross-language health research. AB - OBJECTIVE: Interviews with ethnic minority patients provide a rich source of data to understand their perspectives of disease and its management. Language barriers are, however, often a problem so interpreters need to be used. We explored the impact of the interpreter on cross-language interviews between researchers and respondents. METHODS: Secondary analysis of four interviews between researchers and patients involving professional interpreters. RESULTS: Interpreters were actively involved and influenced the interview in several ways: they assumed the interviewer's communicative role, edited information; initiated information seeking, took over control of the interview, and took over the respondent's role. While the interpreter supported the interviewer, they posed risks to the quality of the interview. CONCLUSION: Researchers need to be aware of the influence of interpreters. Researchers should instruct interpreters carefully about their roles though they may benefit from interpreters' strategies to support them. PMID- 26888478 TI - The problem of representativeness of clinical trial participants: understanding the role of hidden costs. PMID- 26888479 TI - GPER negatively regulates TNFalpha-induced IL-6 production in human breast cancer cells via NF-kappaB pathway. AB - Estrogen is known to have anti-inflammatory effects, that are thought to be mediated by the classical estrogen receptors (ERs), ERalpha and ERbeta. G protein coupled estrogen receptor1 (GPER) is a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic responses. Although there have been several reports asserting that the participation of GPER in anti-inflammatory effects is induced by estrogen, the role of GPER remains poorly understood. In this study, we investigated the involvement of GPER in the regulation of a representative inflammatory cytokine, IL-6. We first examined the expression of IL-6 mRNA by TNFalpha stimulation in the transfection of GPER-expression plasmid into HeLa cells. Exogenous GPER significantly inhibited TNFalpha-induced IL-6 expression, and blocked NF-kappaB promoter activity inducing the expression of IL-6 in a dose dependent manner. The promoter activity was restored almost to control level by transfection with the C-terminal deletion mutant of GPER. Similar results have been observed in endogenous GPER using SKBR3 cells which do not express the classical ERs. The data have been validated by treatment of GPER with siRNA. These findings indicate that GPER negatively regulates TNFalpha-induced IL-6 expression, probably through inhibition of NF-kappaB promoter activity by a signal(s) derived from the C-terminal region of GPER. PMID- 26888481 TI - Increased biomass productivity in green algae by tuning non-photochemical quenching. AB - Photosynthetic microalgae have a high potential for the production of biofuels and highly valued metabolites. However, their current industrial exploitation is limited by a productivity in photobioreactors that is low compared to potential productivity. The high cell density and pigment content of the surface layers of photosynthetic microalgae result in absorption of excess photons and energy dissipation through non-photochemical quenching (NPQ). NPQ prevents photoinhibition, but its activation reduces the efficiency of photosynthetic energy conversion. In Chlamydomonas reinhardtii, NPQ is catalyzed by protein subunits encoded by three lhcsr (light harvesting complex stress related) genes. Here, we show that heat dissipation and biomass productivity depends on LHCSR protein accumulation. Indeed, algal strains lacking two lhcsr genes can grow in a wide range of light growth conditions without suffering from photoinhibition and are more productive than wild-type. Thus, the down-regulation of NPQ appears to be a suitable strategy for improving light use efficiency for biomass and biofuel production in microalgae. PMID- 26888480 TI - A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening. AB - Current animal and 2-D cell culture models employed in metastasis research and drug discovery remain poor mimics of human cancer physiology. Here we describe a "metastasis-on-a-chip" system allowing real time tracking of fluorescent colon cancer cells migrating from hydrogel-fabricated gut constructs to downstream liver constructs within a circulatory fluidic device system that responds to environmental manipulation and drug treatment. Devices consist of two chambers in which gut and liver constructs are housed independently, but are connected in series via circulating fluid flow. Constructs were biofabricated with a hyaluronic acid-based hydrogel system, capable of a variety of customizations, inside of which representative host tissue cells were suspended and metastatic colon carcinoma tumor foci were created. The host tissue of the constructs expressed normal epithelial markers, which the tumor foci failed to express. Instead, tumor regions lost membrane-bound adhesion markers, and expressed mesenchymal and proliferative markers, suggesting a metastatic phenotype. Metastatic tumor foci grew in size, eventually disseminating from the intestine construct and entering circulation, subsequently reaching in the liver construct, thus mimicking some of the migratory events observed during metastasis. Lastly, we demonstrated the ability to manipulate the system, including chemically modulating the hydrogel system mechanical properties and administering chemotherapeutic agents, and evaluated the effects of these parameters on invasive tumor migration. These results describe the capability of this early stage metastasis-on-a-chip system to model several important characteristics of human metastasis, thereby demonstrating the potential of the platform for making meaningful advances in cancer investigation and drug discovery. Biotechnol. Bioeng. 2016;113: 2020-2032. (c) 2016 Wiley Periodicals, Inc. PMID- 26888482 TI - Milder progressive cerebellar atrophy caused by biallelic SEPSECS mutations. AB - Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late onset cerebellar atrophy. PMID- 26888483 TI - Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia. AB - Hereditary spastic paraplegia (HSP) is an extremely heterogeneous disease caused by mutations of numerous genes leading to lower limb spasticity (pure forms) that can be accompanied by neurological symptoms (complex forms). Despite recent advances, many causal mutations in patients remain unknown. We identified a consanguineous family with the early-onset HSP. Whole-exome sequencing revealed homozygosity for a novel Atlastin GTPase 1 gene stop mutation in three affected siblings. Heterozygous parents and siblings were unaffected. This was unexpected as mutations in the Atlastin 1 gene are known to cause autosomal dominant HSP. But our study showed that Atlastin 1 mutations may cause autosomal recessively inherited paraplegia with an underlying loss-of-function mechanism. Hence, patients with recessive forms of HSP should also be tested for the Atlastin 1 gene. PMID- 26888484 TI - Mechanisms and reactivity differences for the cobalt-catalyzed enantioselective intramolecular hydroacylation of ketones and alkenes: insights from density functional calculations. AB - Density functional theory (DFT) was used to study the cobalt(I)-catalyzed enantioselective intramolecular hydroacylation of ketones and alkenes. All intermediates and transition states were fully optimized at the M06/6-31G(d,p) level (LANL2DZ(f) for Co). The results demonstrated that the ketone and alkene present different reactivities in the enantioselective hydroacylation. In ketone hydroacylation catalyzed by the cobalt(I)-(R,R)-Ph-BPE complex, reaction channel "a" to (R)-phthalide was more favorable than channel "b" to (S)-phthalide. Hydrogen migration was both the rate-determining and chirality-limiting step, and this step was endothermic. In alkene hydroacylation catalyzed by the cobalt(I) (R,R)-BDPP complex, reaction channel "c" leading to the formation of (S)-indanone was the most favorable, both thermodynamically and kinetically. Reductive elimination was the rate-determining step, but the chirality-limiting step was hydrogen migration, which occurred easily. The results also indicated that the alkene hydroacylation leading to (S)-indanone formation was more energetically favorable than the ketone hydroacylation that gave (R)-phthalide, both thermodynamically and kinetically. PMID- 26888486 TI - Determination of thiol metabolites in human urine by stable isotope labeling in combination with pseudo-targeted mass spectrometry analysis. AB - Precursor ion scan and multiple reaction monitoring scan (MRM) are two typical scan modes in mass spectrometry analysis. Here, we developed a strategy by combining stable isotope labeling (IL) with liquid chromatography-mass spectrometry (LC-MS) under double precursor ion scan (DPI) and MRM for analysis of thiols in 5 types of human cancer urine. Firstly, the IL-LC-DPI-MS method was applied for non-targeted profiling of thiols from cancer samples. Compared to traditional full scan mode, the DPI method significantly improved identification selectivity and accuracy. 103 thiol candidates were discovered in all cancers and 6 thiols were identified by their standards. It is worth noting that pantetheine, for the first time, was identified in human urine. Secondly, the IL-LC-MRM-MS method was developed for relative quantification of thiols in cancers compared to healthy controls. All the MRM transitions of light and heavy labeled thiols were acquired from urines by using DPI method. Compared to DPI method, the sensitivity of MRM improved by 2.1-11.3 folds. In addition, the concentration of homocysteine, gamma-glutamylcysteine and pantetheine enhanced more than two folds in cancer patients compared to healthy controls. Taken together, the method demonstrated to be a promising strategy for identification and comprehensive quantification of thiols in human urines. PMID- 26888485 TI - Cardioprotective effects of Notoginsenoside R1 against ischemia/reperfusion injuries by regulating oxidative stress- and endoplasmic reticulum stress- related signaling pathways. AB - BACKGROUND: Recent reports suggested the involvement of oxidative stress- and endoplasmic reticulum stress (ERS)-associated pathways in the progression of ischemia/reperfusion (I/R) injury. Notoginsenoside R1 (NGR1) is a novel saponin isolated from P. notoginseng, which has a history of prevention and treatment of cardiovascular diseases. OBJECTIVE: We aimed to examine the cardioprotective effects of NGR1 on I/R-induced heart dysfunction ex vivo and in vitro. METHODS: H9c2 cadiomyocytes were incubated with NGR1 for 24 h and exposed to hypoxia/reoxygenation. Isolated rat hearts were perfused by NGR1 for 15 min and then subjected to global ischemia/reperfusion. Hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), heart rate, and maximal rate of increase and decrease of left ventricular pressure (+/- dP/dt max/min). RESULTS: NGR1 pretreatment prevents cell apoptosis and delays the onset of ERS by decreasing the protein expression levels of ERS-responsive proteins GRP78, P PERK, ATF6, IRE, and inhibiting the expression of pro-apoptosis proteins CHOP, Caspase-12, and P-JNK. Besides, NGR1 scavenges free radical, and increases the activity of antioxidase. NGR1 inhibits Tunicamycin-induced cell death and cardiac dysfunction. CONCLUSION: We elucidated the significant cardioprotective effects of NGR1 against I/R injuries, and demonstrated the involvement of oxidative stress and ERS in the protective effects of NGR1. PMID- 26888487 TI - Diet supplementation with cinnamon oil, cinnamaldehyde, or monensin does not reduce enteric methane production of dairy cows. AB - This study was conducted to evaluate the effect of dietary addition of cinnamon oil (CIN), cinnamaldehyde (CDH), or monensin (MON) on enteric methane (CH4) emission in dairy cows. Eight multiparous lactating Holstein cows fitted with ruminal cannulas were used in a replicated 4*4 Latin square design (28-day periods). Cows were fed (ad libitum) a total mixed ration ((TMR); 60 : 40 forage : concentrate ratio, on a dry matter (DM) basis) not supplemented (CTL), or supplemented with CIN (50 mg/kg DM intake), CDH (50 mg/kg DM intake), or monensin (24 mg/kg of DM intake). Dry matter intake (DMI), nutrient digestibility, N retention, and milk performance were measured over 6 consecutive days. Ruminal degradability of the basal diet (with no additive) was assessed using in sacco incubations (0, 2, 4, 8, 16, 24, 48, 72 and 96 h). Ruminal fermentation characteristics (pH, volatile fatty acids (VFA), and ammonia (NH3)) and protozoa were determined over 2 days. Enteric CH4 emissions were measured over 6 consecutive days using the sulfur hexafluoride (SF6) tracer gas technique. Adding CIN, CDH or MON to the diet had no effects on DMI, N retention, in sacco ruminal degradation and nutrient digestibility of the diet. Ruminal fermentation characteristics and protozoa numbers were not modified by including the feed additives in the diet. Enteric CH4 emission and CH4 energy losses averaged 491 g/day and 6.59% of gross energy intake, respectively, and were not affected by adding CIN, CDH or MON to the diet. Results of this study indicate that CIN, CDH and MON are not viable CH4 mitigation strategies in dairy cows. PMID- 26888488 TI - Role of ADAMTS1 and ADAMTS5 in male infertility. AB - The aim of this study was to investigate the relationship of infertility with metalloproteinases ADAMTS1 and ADAMTS5, which are known to be responsible for the degradation of extracellular matrix (ECM) proteins associated with many diseases. ECM is the noncellular component that provides structural and biochemical support to the surrounding cells required for tissue morphogenesis, differentiation and homoeostasis. Sixty infertile individuals and 10 healthy semen donors were included in this study. The infertile individuals were classified as normozoospermia (NS; n = 20), oligozoospermia (OS; n = 20), azoospermia (AS; n = 20) groups. ADAMTS1 and ADAMTS5 protein levels in semen were analysed by Western blot. ADAMTS1 protein level was 3.0-, 3.3- and 1.6-fold lower in the OS, AS and NS groups, respectively, than in the control group (P < 0.001). ADAMTS5 protein level was 3.2-, 2.7- and 1.4-fold lower in the OS, AS and NS groups, respectively, than in the control group (P < 0.001). Sperm count and sperm motility showed a negative correlation with the levels of ADAMTS1 and ADAMTS5 protein expression: r = -0.477, r = -0.470; and r = -0.332, r = -0.275 respectively (P < 0.001). In conclusion, ADAMTS1 and ADAMTS5 protein expressions in semen are significantly related with sperm production. It is very important to understand molecular function and organisation of ADAMTSs which will be significant in enlightening the process of spermatogenesis in male infertility. PMID- 26888489 TI - Influence of berry ripeness on accumulation, composition and extractability of skin and seed flavonoids in cv. Sangiovese (Vitis vinifera L.). AB - BACKGROUND: The anthocyanin and tannin concentration and composition of Vitis vinifera L. cv. Sangiovese berries were investigated from post-veraison to harvest. Exhaustive extraction with methanol and acetone was performed to determine the total flavonoid concentration, while a model hydroalcoholic solution was used to prepare extracts representing the winemaking process. The aim of this study was to improve the knowledge of the phenolic maturity of Sangiovese grape. RESULTS: The total anthocyanin concentration increased during ripening, but the quantity of extractable anthocyanins increased more rapidly than the total. The total skin tannin concentration declined from post-veraison to harvest, whereas the extractable portion increased, with little difference in the composition of the fractions. Both the total and extractable seed tannin concentration diminished rapidly just after veraison, and only small fluctuations were detected until harvest. CONCLUSION: These results indicate that the extractability of anthocyanins and skin tannins increases during ripening, whereas there is no clear trend for seed tannins during the same period. This is the first survey to study the behavior of phenolic compounds during different steps of ripening of Sangiovese grape. (c) 2016 Society of Chemical Industry. PMID- 26888491 TI - Chiral tunneling in gated inversion symmetric Weyl semimetal. AB - Based on the chirality-resolved transfer-matrix method, we evaluate the chiral transport tunneling through Weyl semimetal multi-barrier structures created by periodic gates. It is shown that, in sharp contrast to the cases of three dimensional normal semimetals, the tunneling coefficient as a function of incident angle shows a strong anisotropic behavior. Importantly, the tunneling coefficients display an interesting periodic oscillation as a function of the crystallographic angle of the structures. With the increasement of the barriers, the tunneling current shows a Fabry-Perot type interferences. For superlattice structures, the fancy miniband effect has been revealed. Our results show that the angular dependence of the first bandgap can be reduced into a Lorentz formula. The disorder suppresses the oscillation of the tunneling conductance, but would not affect its average amplitude. This is in sharp contrast to that in multi-barrier conventional semiconductor structures. Moreover, numerical results for the dependence of the angularly averaged conductance on the incident energy and the structure parameters are presented and contrasted with those in two dimensional relativistic materials. Our work suggests that the gated Weyl semimetal opens a possible new route to access to new type nanoelectronic device. PMID- 26888492 TI - Autosomal dominant polycystic kidney disease and coronary artery dissection or aneurysm: a systematic review. AB - IMPORTANCE: Autosomal dominant polycystic kidney disease (ADPKD) has been associated with cardiovascular abnormalities such as intracranial and aortic aneurysms. OBJECTIVE: To systematically review the case reports and case series of ADPKD patients with coronary artery dissection or aneurysm. Evidence review Systematic review registration number: CRD42015015723. DATA SOURCES: MEDLINE, Web of Science and OpenGrey, reference lists of studies. STUDY SELECTION: Published case reports and case series. DATA EXTRACTION: Two parties analyzed the studies. Disagreements were solved by consensus or by a third party. FUNDING: none. Findings The reports of 23 patients (22 from 17 studies--six with coronary artery dissection and 16 with coronary artery aneurysm--and one with coronary dissection) were analyzed and reported here. Most patients were symptomatic. Coronary dissection showed female and left descending anterior artery predominance, features similar to non-ADPKD patients, but a median diagnostic age below expected (41 vs. 50 years old). Coronary aneurysms had male and right coronary artery predominance but lower median diagnostic age (44 years old) and higher rate of multiple vessel affection than reported for non-ADPKD patients. CONCLUSION AND RELEVANCE: Clinical disparities may suggest a different mechanism of aneurysm formation compared to the population without ADPKD. Nevertheless, lack of access to data of one patient and text of one article limited our conclusions. Coronary aneurysms and dissections represent a source of coronary syndromes and death in ADPKD. Mutation of ADPKD-related genes may predispose to coronary abnormalities, especially aneurysms. Further analysis regarding this association is necessary. PMID- 26888490 TI - Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood. AB - Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17-1.51, for BMI 35+ vs <22.5 kg/m(2)), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10-1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small. PMID- 26888493 TI - Highly efficient and selective enrichment of glycopeptides using easily synthesized magG/PDA/Au/l-Cys composites. AB - Highly selective and efficient enrichment of glycopeptides from complex biological samples is necessary. In this study, novel zwitterionic hydrophilic polydopamine-coated magnetic graphene composites (magG/PDA/Au/l-Cys) were synthesized and applied to the enrichment of glycopeptides. The size, morphology, and composition of magG/PDA/Au/l-Cys composites were investigated by transmission electron microscopy, scanning electron microscopy, FT-infrared spectroscopy, and X-ray diffraction. The composites possessed a number of desirable characteristics, including good biocompatibility easy separation property and excellent hydrophilicity. By virtue of the features contributed by different ingredients, the prepared composites demonstrated superior performance for glycopeptide enrichment with high sensitivity (0.1 fmol), efficiency, selectivity (1:100), and repeatability (at least ten times). In addition, the composites were successfully applied to the enrichment of glycopeptides from human serum and 40 unique N-glycosylation peptides from 31 different N-linked glycoproteins were identified. The superior hydrophilic material is of great potential for the analysis of glycoproteins. PMID- 26888494 TI - Major acid endopeptidases of the blood-feeding monogenean Eudiplozoon nipponicum (Heteronchoinea: Diplozoidae). AB - In parasitic flatworms, acid endopeptidases are involved in crucial processes, including digestion, invasion, interactions with the host immune system, etc. In haematophagous monogeneans, however, no solid information has been available about the occurrence of these enzymes. Here we aimed to identify major cysteine and aspartic endopeptidase activities in Eudiplozoon nipponicum, an invasive haematophagous parasite of common carp. Employing biochemical, proteomic and molecular tools, we found that cysteine peptidase activities prevailed in soluble protein extracts and excretory/secretory products (ESP) of E. nipponicum; the major part was cathepsin L-like in nature supplemented with cathepsin B-like activity. Significant activity of the aspartic cathepsin D also occurred in soluble protein extracts. The degradation of haemoglobin in the presence of ESP and worm protein extracts was completely inhibited by a combination of cysteine and aspartic peptidase inhibitors, and diminished by particular cathepsin L, B and D inhibitors. Mass spectrometry revealed several tryptic peptides in ESP matching to two translated sequences of cathepsin L genes, which were amplified from cDNA of E. nipponicum and bioinformatically annotated. The dominance of cysteine peptidases of cathepsin L type in E. nipponicum resembles the situation in, e.g. fasciolid trematodes. PMID- 26888495 TI - [Retrospect and prospect on hematolymphoid pathology in last decade of China]. PMID- 26888496 TI - [Retrospect and prospect on neuropathology in last decade of China]. PMID- 26888497 TI - [Retrospect and prospect on gynecological pathology in last decade of China]. PMID- 26888498 TI - [Retrospect and prospect on experimental pathology in last decade of China]. PMID- 26888499 TI - [Retrospect and prospect on cytopathology in last decade of China]. PMID- 26888500 TI - [Retrospect on quality control of department of pathology in last six decades of China]. PMID- 26888501 TI - [Small cell carcinoma of ovary, hypercalcemic type: analysis of clinicopathologic characteristics and the diagnostic utility of loss expression of SMARCA4 protein]. AB - OBJECTIVE: To study the clinicopathologic features of small cell carcinoma of ovary, hypercalcemic type (SCCOHT) and to evaluate the diagnostic significance of loss of SMARCA4 expression. METHODS: The clinicopathologic characteristics of 5 cases of SCCOHT were reviewed. The expression of SMARCA4 protein was detected by immunohistochemistry in the cases of SCCOHT and 240 cases of other primary malignant tumors of ovary and peritoneum. RESULTS: The mean and medium age of these patients was 30 years and 28 years, respectively. The presenting symptoms included abdominal pain, distention and a pelvic mass. Hypercalcemia was found in 3 patients. The maximum diameter of tumors ranged from 13.5 to 22.0 cm. Extraovarian spread was demonstrated in all of the patients on presentation. Histologically, the tumors were composed of closely packed small round cells with scanty cytoplasm, hyperchromatic nuclei and irregular chromatin clumps. The tumor cells grew in sheets, nests, cords or trabecular pattern. Follicle-like spaces were observed in 4 cases. Three of the tumors contained large cells with abundant eosinophilic cytoplasm. Spindle cell morphology was found in 1 case. There were 2 cases with myxoid or hyaline stroma. Four out of five of SCCOHT cases showed loss of SMARCA4 protein while only 6.3% (15/240) of the other primary malignant tumors of ovary and peritoneum , including undifferentiated carcinoma (1/5), high-grade serous carcinoma (4.6%, 5/109), endometrioid carcinoma (7.7%, 2/26), clear cell carcinoma (1/9), mucinous carcinoma (1/5), mixed carcinoma (4.9%, 3/61), carcinosarcoma (1/9) and high-grade serous carcinoma of peritoneum (1/9), were negative. CONCLUSIONS: SCCOHT is a rare malignant tumor and often misdiagnosed as other types of ovarian small cell tumor. Loss expression of SMARCA4 protein is characteristic and facilitates the diagnosis and differential diagnosis of SCCOHT. PMID- 26888502 TI - [Pathological change of histologic chorioamnionitis and its association with neonatal inflammation]. AB - OBJECTIVE: To investigate the pathologic features of histologic chorioamnionitis (HCA) and its impact on newborns. METHODS: From Jun.2012 to Dec.2014, 5 810 placentas delivered in our hospital were collected. There were 898 HCA cases and positive rate was 18.3%.Cases with complete clinical data were collected, including 308 cases of infected newbon infants (case group), and 120 cases of non infected infants(control group). The correlation between pathologic results and neonatal outcome was analyzed. RESULTS: Thirty nine cases were premature delivery (39/428, 9.1%). Twenty one cases were small for gestational age (21/428, 4.9%). One hundred and eleven cases were delivered by caesarean section (111/428, 25.9%). Three hundred and eight cases of neonatal infection included 104 cases of hematosepsis, 16 cases of purulent meningitis, 78 cases of infectious pneumonia, 34 cases of infective enteritis, 18 cases of urinary tract infection and 58 cases of skin infection.Placental pathological examination found out 40 cases showed mild HCA (18 cases of neonatal infection, and 22 non-neonatal infection cases), 104 cases showed moderate HCA (88 cases of neonatal infection, and 16 non neonatal infection cases), and 183 cases showed severe HCA (172 cases of neonatal infection and 11 non-neonatal infection cases). Moderate to severe HCA were easily found in premature infants, with higher positive rate of both late pregnancy group B streptococcus (P<0.05) and afterbirth blood culture (P<0.05). Significantly higher serum C reaction protein (P<0.05) and white-cell count(P<0.05) were also found within moderate to severe HCA patients. Moderate to severe HCA, funisitis and syncytial nodular hyperplasia were associated with neonatal infections (P<0.05), while infarction, intervillous thrombosis and villi thrombus were not observed in the inflammation group (P>0.05). CONCLUSIONS: HCA is often of few clinical symptoms and easily misdiagnosed by placental pathological assessment only. HCA is found associated with intrauterine infection and neonatal infection. Pathological assessment of placenta is valuable in diagnosis and treatment of intrauterine infection. PMID- 26888503 TI - [Diagnostic utility of STR genotyping for partial hydatidiform moles]. AB - OBJECTIVE: To investigate the clinical utility of short tandem repeats(STR) genotyping technique for diagnosis of partial hydatidiform moles (PHM). METHODS: Ten cases with the original diagnosis of PHM and six cases diagnosed as "favour PHM" or "abnormal villous, PHM not excluded" were selected for the study. The clinical information and follow-up data were reviewed. Histopathologic features were evaluated along with p57 immunohistochemistry. After DNA extraction from each sample, genotyping was performed by AmpFlSTR((r)) IdentifilerTM PCR kit to amplify 15 STR polymorphism loci plus the amelogenin gender-determining in a single robust PCR. RESULTS: The age of patients ranged from 18 to 49 years (mean=29 years, median=29 years). Two villous populations (7/16), irregular villous contour (13/16), at least moderate trophoblastic hyperplasia (2/16), cistern formation (8/16), syncytiotrophoblastic knuckles (14/16), trophoblastic pseudoinclusions (6/16) and nucleated fetal red blood cells (8/16) were presented in these cases. Of the cases in the study, STR genotyping identified 4 monospermic complete hydatidiform moles (MCM), 3 dispermic partial hydatidiform moles (DPM) and 9 hydropic abortions (HA). The misdiagnosis rate was 13/16 only relied on morphology evaluation. Immunostaining of p57 showed 3/4 of MCM were focally positive (<5%-20%+), 1/4 of MCM were diffusely positive (70%+), 3/3 of DPM were diffusely positive (>=50%+), 7/9 of HA were diffusely positive (>=50%+), and 2/9 of HA were focally positive (10%+). CONCLUSIONS: Combination of histomorphologic evaluation and p57 immunostaining is insufficient for a definitive diagnosis of PHM. STR genotyping offers an accurate diagnosis of PHM. PMID- 26888504 TI - [Diagnostic value of combined detection of HNF-1beta and Napsin A in the diagnosis of ovarian clear cell carcinoma]. AB - OBJECTIVE: To study the diagnostic value of HNF-1beta and Napsin A for ovarian clear cell carcinomas, serous carcinomas, endometrioid adenocarcinomas and metastatic Krukenberg tumors. METHODS: Immunohistochemical EnVision method was used to detect the expression of HNF-1beta and Napsin A in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma and 16 cases of metastatic Krukenberg tumor. Expression of HNF-1beta and Napsin A were compared, and sensitivity and specificity of clear cell carcinoma of the ovary were analysed. RESULTS: The positive rate of HNF-1beta in the ovarian clear cell carcinoma was 100%(38/38), higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P<0.05), although significant difference was not observed from that of metastatic Krukenberg tumor (P>0.05). Napsin A expressed in 97.4% (37/38) of ovarian clear cell carcinoma, 6.7% (2/30) of high-grade serous carcinoma, 22.7% (5/22) of endometrioid adenocarcinoma. Napsin A expression in clear cell carcinoma was higher than those in high-grade serous carcinoma and endometrioid adenocarcinoma (P<0.01), and no expression of Napsin A was seen in metastatic Krukenberg tumor (P>0.05). The sensitivity and specificity of HNF-1beta in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, those of Napsin A were 97.4% and 91.2%, those of both HNF-1beta and Napsin A were 97.4% and 91.2%, respectively. The sensitivity and specificity of HNF-1beta or Napsin A in the diagnosis of ovarian clear cell carcinoma were 100% and 52.9%, respectively. CONCLUSIONS: HNF-1beta is a more sensitive marker for the diagnosis of ovarian clear cell carcinoma, whereas Napsin A is a more specific marker. The combined detection of HNF-1beta and Napsin A may be helpful for the diagnosis of clear cell carcinoma of the ovary. PMID- 26888505 TI - [Early and late onset severe preeclampsia: a clinicopathologic study of 178 placentas]. AB - OBJECTIVE: To explore the pathologic features and prognosis of early and late onset severe preeclampsia. METHODS: An observational study was conducted in 178 cases of severe preeclampsia collected during January 2010 to December 2014 from Haidian Maternal and Child Health Hospital.The cases were divided into two groups according to the onset of gestational age of the severe preeclampsia, with 54 cases of namely early onset (onset <= 34 weeks) and 124 cases of late onset (onset >34 weeks). Clinical characteristics of the patients, perinatal outcome and the pathologic characteristics of the placentas in each group were evaluated. RESULTS: Decidual vascular disease, placental infarction, abruptio placentae and placental villi dysplasia were seen in both groups. The incidence of placental villi dysplasia was the highest, followed by placental infarction. Incidence of severe decidual vascular disease of early and late onset severe decidual vascular disease were 16.7% (9/54) and 5.6% (7/124), respectively.Incidence of placental infarction of early and late onset severe preeclampsia were 48.1% (26/54) and 61.3% (76/124). Incidence of placental villi dysplasia of early and late onset severe preeclampsia were 79.6% (43/54) and 50.8% (63/124). Incidence of Severe decidual vascular disease, placental infarction and placental villi dysplasia were significantly different between early and late onset severe preeclampsia cases (P<0.05), while there was no difference in decidual vascular disease and placenta thrombi (P>0.05). Fetal survival rate of every group was 81.5% (44/54) and 93.5% (116/124). Incidence of fetal growth retardation was 55.6% (30/54) and 38.7% (48/124). The fetal survival rate and incidence of fetal growth retardation were different between two groups (P<0.05). CONCLUSIONS: The incidence of decidual vascular disease and placental villi dysplasia in early onset severe preeclampsia is higher than those in late onset severe preeclampsia. Neonatal outcome and prognosis in early onset severe preeclampsia are worse than those in late onset severe preeclampsia. PMID- 26888506 TI - [Expression of cyclin D1 in cervical intraepithelial neoplasia and squamous cell carcinoma and its relationship with HPV16 E7 gene]. AB - OBJECTIVE: To investigate the expression of cyclin D1 in cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma and its relationship with human papillomavirus 16 (HPV16) E7 gene expression. METHODS: Both SiHa and Hcc94 cell lines were obtained from cervical epithelial cells of squamous cell carcinoma. E6/E7 gene was silent in Hcc94 cell line.Expression levels of cyclin D1 mRNA and protein in CIN and squamous cell carcinoma were detected by QT-PCR and immunohistochemistry (IHC) respectively. SiRNA was constructed for targeting the promoter of HPV16 E7 and then transfected into SiHa cells to establish cm-16 line with stable silencing of E7. Control cell line B3 was obtained by blank plasmid transfection into SiHa cells. RT-PCR and Western blot were used to detect cyclin D1 mRNA and protein expression in the SiHa, B3, and cm-16 cells, respectively. RESULTS: Cyclin D1 was expressed in the basal cells of normal cervical squamous epithelia and the expression gradually decreased in the progression from CIN1 to CIN3. Squamous cell carcinoma showed negative or scattered expression of cyclin D1 (P<0.05). Both mRNA and protein of cyclin D1 in E7(+) SiHa cells were lower than those in cm-16 and Hcc94 cells. CONCLUSION: Squamous cell carcinoma with high HPV E7 expression shows low level of cyclin D1, suggesting that HPV16 E7 gene inhibits the expression of cyclin D1. PMID- 26888507 TI - [Clinicopathologic features of embryonal tumor with multilayered rosettes and gene analysis on chromosome 19q13.42]. AB - OBJECTIVE: To investigate the clinicopathologic features and 19q13.42 gene changes in embryonal tumors with multilayered rosettes (ETMR). METHODS: Immunohistochemistry and fluorescence in situ hybridization (FISH) were performed in three ETMRs. RESULTS: The average age of the patients were 34 months. Imaging revealed huge masses with inhomogeneous enhancement and two cases showed cystic lesions. Follow-up data showed 14 and 38 months survival in two children, the third had a recurrence 4 months after operation. Morphologically, the tumor was mainly composed of dense small primitive neuroepithelial cells in patchy or multilayer rosettes within a background of advanced neuronal differentiation, containing neurocytes, ganglion cells, and neuropil-like background. Immunohistochemical staining showed the neuronal marker, synaptophysin, was positive in differentiated areas. Nestin as a neural stem cell marker was immunoreactive in the primitive neuroepithelial cells including multilayered rosettes. Neurons with positive expression of NeuN were observed occasionally. Ki 67 index was up to 40%-80% in the undifferentiated cells and rosettes, but was only 1%-3% in the differentiated areas. CD99 was positive in perivascular papillary pattern areas in one case. 19q13.42 amplification was detected in more than 30% of tumor cells in all cases. CONCLUSIONS: ETMR is a unique entity with distinctive clinical and pathological features. Chromosome 19q13.42 abnormality is valuable for confirming the diagnosis and for further treatment research. PMID- 26888508 TI - [Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis]. AB - OBJECTIVE: To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion. METHODS: A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature. RESULTS: The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis. CONCLUSIONS: TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis. PMID- 26888509 TI - [Middle ear adenoma: clinical and pathologic analysis]. AB - OBJECTIVE: To investigate the clinical and pathologic features of middle ear adenoma (MEA). METHODS: Eight cases of MEA were collected from Beijing Tongren Hospital, Capital Medical University between 2004 and 2014, and immunohistochemical staining was performed. RESULTS: The patients included five women and three men (mean age, 37.5 years; median 37 years; range, 21-51 years). All patients had unilateral lesions. Five MEA occurred on the left side, and three on the right. In seven patients the MEA was primary, and they presented with hearing loss (6 cases), tinnitus (5 cases), sense of ear blockage (3 cases), otalgia (1 case) and facial nerve paralysis (1 case). The remaining patient had recurrent MEA, and presented with otorrhea, aural fullness and tinnitus. Histologically, the tumor cells were arranged in a variety of patterns, including solid sheets, nests, glands, ribbons or trabeculae. Glandular structures were prominent in one case only. Immunohistochemically, the tumor cells were diffusely positive for keratin (8/8) and vimentin (8/8), and focally positive for CK 7(8/8) and CK5/6(8/8). CK7 and CK5/6 were predominantly positive in tumor cells with glandular growth pattern; CK7 was positive in the luminal cells while CK5/6 was positive in the abluminal cells. Both were also expressed focally in scattered tumor cells with non-glandular pattern. The tumor cells were also diffusely positive for synaptophysin(8/8), diffusely but weakly positive for NSE (5/8), and were diffusely or focally positive for chromogranin A (4/8). Both S-100 protein and calponin were negative in all cases. The proliferation rate was low, about 1% 2%. Six cases were followed up for one year and three months to ten years and six months, with an average follow-up period of four years and two months. Two patients developed recurrence, but there were no regional or distant metastases. CONCLUSIONS: Diagnosis of MEA requires pathologic confirmation since the clinical symptoms are non-specific. MEA can show a variety of histologic patterns, and should be distinguished from other space-occupying lesions at this site. Immunohistochemical staining has greatly contributed to the diagnosis and differential diagnosis of MEA. The prognosis of this tumor is good. Patients with MEA require long-term follow-up for recurrences. PMID- 26888510 TI - [Expression levels of miR-181c-3p and miR-5692b in esophageal cancer and their clinical significance]. AB - OBJECTIVE: To study the expression level and clinical significance of miR-181c-3p and miR-5692b in esophageal cancer. METHODS: The microRNA (miRNA) profiles of esophageal squamous cell carcinoma were analyzed by miRNA microarray in 55 cases of esophageal cancer. The expression levels of miR-181c-3p and miR-5692b from 55 pairs of tumor tissues and adjacent non-neoplastic tissues were determined by qRT PCR analysis. RESULTS: Both miR-181c-3p and miR-5692b were significantly up regulated in tumor tissues compared with adjacent non-neoplastic tissues. Their expression was also significantly associated with tumor size, depth of invasion and clinical tumor stage (P<0.05). High expression of miR-181c-3p and miR-5692b were significantly associated with poor prognosis (P<0.05). Multivariate Cox regression analysis confirmed that high expression of miR-181c-3p and miR-5692b was poor prognostic indicators in esophageal cancer. CONCLUSIONS: There are significant correlation between miR-181c-3p/miR-5692b expression, clinicopathologic parameters and prognosis. They represent potential prognostic biomarkers in esophageal squamous cell carcinoma. PMID- 26888511 TI - [Sinonasal-type hemangiopericytoma: reports of two cases and review of the literature]. PMID- 26888512 TI - [NUT midline carcinoma of sinonasal tract: report of a case]. PMID- 26888513 TI - [Pulmonary fibroleiomyomatous hamartoma: report of a case]. PMID- 26888514 TI - [Duodenal medullary carcinoma: report of a case]. PMID- 26888515 TI - [Hepatic desmoid type fibromatosis: report of a case]. PMID- 26888516 TI - [Gastrointestinal stromal tumor with foam cell-like and micro-capsule structures: report of a case]. PMID- 26888517 TI - [Recent progress in diagnosis and classification of ovarian germ cell tumors]. PMID- 26888518 TI - [Study of relationship of long noncoding RNA, microRNA and epigenetics]. PMID- 26888519 TI - Building the Leviathan--Voluntary centralisation of punishment power sustains cooperation in humans. AB - The prevalence of cooperation among humans is puzzling because cooperators can be exploited by free riders. Peer punishment has been suggested as a solution to this puzzle, but cumulating evidence questions its robustness in sustaining cooperation. Amongst others, punishment fails when it is not powerful enough, or when it elicits counter-punishment. Existing research, however, has ignored that the distribution of punishment power can be the result of social interactions. We introduce a novel experiment in which individuals can transfer punishment power to others. We find that while decentralised peer punishment fails to overcome free riding, the voluntary transfer of punishment power enables groups to sustain cooperation. This is achieved by non-punishing cooperators empowering those who are willing to punish in the interest of the group. Our results show how voluntary power centralisation can efficiently sustain cooperation, which could explain why hierarchical power structures are widespread among animals and humans. PMID- 26888520 TI - Urinary deoxynivalenol (DON) and zearalenone (ZEA) as biomarkers of DON and ZEA exposure of pigs. AB - Four diets contaminated with 1.1 to 5.0 mg/kg deoxynivalenol (DON) and 0.4 to 2.4 mg/kg zearalenone (ZEA) were fed to four groups of six growing Large White pigs. Urine samples were collected after 3 to 4 days and again after 6 to 7 days on the diets. On each sampling day, half of the animals were sampled in the morning, after an 8-h fast, and the other half were sampled in the afternoon, after 7 h of ad libitum access to feed. The urinary concentrations of DON, DON-glucuronide, DON-3-sulphate, de-epoxy-DON, as well as of ZEA, ZEA-14-glucuronide, alpha zearalenol and alpha-zearalenol-14-glucuronide, analysed using LC-MS/MS, were used to calculate urinary DON and ZEA equivalent concentrations (DONe and ZEAe). The urinary concentration of DONe (P < 0.001), but not of ZEAe (P = 0.31), was lower in the fasted than that in the fed animals. The urinary DONe/creatinine and ZEAe/creatinine ratios were highly correlated with DON and ZEA intake per kg body weight the day preceding sampling (r = 0.76 and 0.77; P < 0.001). The correlations between DON intake during the 7 h preceding urine sampling in the afternoon and urinary DONe/creatinine ratio (r = 0.88) as well as between mean ZEA intake during 3 days preceding urine sampling and urinary ZEAe/creatinine ratio (r = 0.84) were even higher, reflecting the plasma elimination half-time of several hours for DON and of more than 3 days for ZEA. ZEAe analysed in enzymatically hydrolysed urine using an ELISA kit was highly correlated with the LC-MS/MS data (r = 0.94). The urinary DONe and ZEAe to creatinine ratios, analysed in pooled urine samples of several pigs fed the same diet, can be used to estimate their exposure to DON and ZEA. PMID- 26888521 TI - Screening for illicit drugs in pooled human urine and urinated soil samples and studies on the stability of urinary excretion products of cocaine, MDMA, and MDEA in wastewater by hyphenated mass spectrometry techniques. AB - Monitoring population drug use through wastewater-based epidemiology (WBE) is a useful method to quantitatively follow trends and estimate total drug consumption in communities. Concentrations of drug biomarkers might be low in wastewater due to dilution; and therefore analysis of pooled urine (PU) is useful to detect consumed drugs and identify targets of illicit drugs use. The aims of the study were (1) to screen PU and urinated soil (US) samples collected at festivals for illicit drug excretion products using hyphenated techniques; (2) to develop and validate a hydrophilic interaction liquid chromatography - mass spectrometry / mass spectrometry (HILIC-MS/MS) method of quantifying urinary targets of identified drugs in wastewater; and (3) to conduct a 24 h stability study, using PU and US to better reflect the chemical environment for targets in wastewater. Cocaine (COC) and ecstasy-like compounds were the most frequently detected illicit drugs; an analytical method was developed to quantify their excretion products. Hydroxymethoxymethamphetamine (HMMA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), HMMA sulfate (HMMA-S), benzoylecgonine (BE), and cocaethylene (CE) had 85-102% of initial concentration after 8 h of incubation, whereas COC and ecgonine methyl ester (EME) had 74 and 67% after 8 h, respectively. HMMA showed a net increase during 24 h of incubation (107% +/- 27, n = 8), possibly due to the cleavage of HMMA conjugates, and biotransformation of MDMA. The results suggest HMMA as analytical target for MDMA consumption in WBE, due to its stability in wastewater and its excretion as the main phase I metabolite of MDMA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888522 TI - One-pot environmentally friendly amino acid mediated synthesis of N-doped graphene-silver nanocomposites with an enhanced multifunctional behavior. AB - The present paper reports the one-pot synthesis of N-doped graphene-Ag nanocomposites (N-GrAg) involving the in situ generation of Ag nanoparticles (NPs). The simultaneous reduction of GO and Ag(+) to produce N-GrAg has been achieved under mild reaction conditions using an environmentally benign reducing agent, glycine, in aqueous medium without adding any external stabilizer. XRD and SAED analyses revealed the presence of Ag in the fcc structure. HRTEM analysis shows a 'd' spacing of 0.236 nm corresponding to the highest intensity (111) reflection of Ag which matches the fcc structure. The N-doping of graphene and its uniform decoration by Ag NPs (with an av. dia. of 17.5 nm) having a relatively low surface atomic % of Ag (0.309) are evidenced by TEM and XPS analyses. Raman spectroscopy has also revealed that the decoration of N-Gr with Ag NPs resulted in the enhancement of the D and G bands by about 365%. The presence of Ag in N-GrAg prevents the folding of the graphene sheet as was revealed by TEM analysis. The supramolecular interactions of Ag with different moieties of N in N-GrAg were evidenced by IR, (13)C NMR and XPS analyses, which resulted in the enhancement of its surface area and electrical conductivity as compared to that of N-Gr. The presence of Ag NPs on N-Gr increased the current response in cyclic voltammetry by more than seven fold as compared to that of N Gr. These nanocomposites exhibited a fairly high SERS activity for 4 aminothiophenol, employed as the probe molecule, and allowed its detection at a 50 nM concentration even for the fairly small sized Ag NPs used in the present work. PMID- 26888523 TI - Toxicity Overrides Morphology on Cylindrospermopsis raciborskii Grazing Resistance to the Calanoid Copepod Eudiaptomus gracilis. AB - Toxicity and morphology may function as defense mechanisms of bloom-forming cyanobacteria against zooplankton grazing. Yet, the relative importance of each of these factors and their plasticity remains poorly known. We tested the effects of chemical and morphological traits of the bloom-forming cyanobacterium Cylindrospermopsis raciborskii on the feeding response of the selective feeder Eudiaptomus gracilis (Calanoida, Copepoda), using a saxitoxin-producing strain (STX+) and a non-saxitoxin (STX-)-producing strain as food. From these two chemotypes, we established cultures of three different morphotypes that differed in filament length (short, medium, and long) by incubating the strains at 17, 25, and 32 degrees C. We hypothesized that the inhibitory effects of saxitoxins determine the avoidance of C. raciborskii, and that morphology would only become relevant in the absence of saxitoxins. Temperature affected two traits: higher temperature resulted in significantly shorter filaments in both strains and led to much higher toxin contents in the STX+ strain (1.7 MUg eq STX L(-1) at 17 degrees C, 7.9 MUg eq STX L(-1) at 25 degrees C, and 25.1 MUg eq STX L(-1) at 32 degrees C). Copepods strongly reduced the ingestion of the STX+ strain in comparison with STX- cultures, regardless of filament length. Conversely, consumption of shorter filaments was significantly higher in the STX- strain. The great plasticity of morphological and chemical traits of C. raciborskii and their resultant contrasting effects on the feeding behavior of zooplankton might explain the success of this cyanobacterium in a variety of aquatic environments. PMID- 26888525 TI - Erratum to: Development of a magnetic coagulant based on Moringa oleifera seed extract for water treatment. PMID- 26888524 TI - Functional Analysis of Vibrio vulnificus Orthologs of Escherichia coli RraA and RNase E. AB - RNase E plays an important role in the degradation and processing of RNA in Escherichia coli. The enzymatic activity of RNase E is controlled by the protein inhibitors RraA and RraB. The marine pathogenic bacterium Vibrio vulnificus also contains homologs of RNase E and RraA, designated as RNase EV, RraAV1, and RraAV2. Here, we report that RraAV1 actively inhibits the enzymatic activity of RNase EV in vivo and in vitro by interacting with the C-terminal domain of RNase EV. Coexpression of RraAV1 reduced ribonucleolytic activity in the cells overproducing RNase EV and consequently restored normal growth of these cells. An in vitro cleavage assay further demonstrated that RraAV1 efficiently inhibits the ribonucleolytic activity of RNase EV on BR10 + hpT, a synthetic oligonucleotide containing the RNase E cleavage site of RNA I. Our findings suggest that RraAV1 plays an active role in RNase EV-mediated RNA cleavage in V. vulnificus. PMID- 26888526 TI - Competitive immunoassay for analysis of bisphenol A in children's sera using a specific antibody. AB - Bisphenol A (BPA) has been reported as a potential estrogenic substance that could affect human health and reproduction. In this study, a monoclonal antibody (Mab) against BPA was produced after the immunization of Balb/c mice with a conjugate of 4,4-bis (4-hydroxyphenyl) valeric acid coupling with keyhole limpet hemocyanin (BVA-KLH). The obtained Mab showed higher affinity against BPA and lower cross-reactivity toward 4,4'-sulfonyldiphenol, diphenolic acid, hydroquinone, salicylic acid, and other common phenolic compounds. Basing on the Mab, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed. Under the optimal conditions, the limit of detection (LOD) was found to be 0.1 ng mL(-1) with the linear working range of 0.45-10.56 ng mL(-1). After sample extraction, the fortified serum samples were detected with intra- and inter-assay recovery ranges of 81.2-92.9 and 84.4-94.4 %, respectively. Then, 100 children's sera were screened by ic-ELISA. The result showed that 54 % of the serum samples were BPA-positive. The positive samples were purified by immuno affinity column (IAC) and further confirmed by high-performance liquid chromatography (HPLC) with fluorescence detector measured at lambda ex/lambda em 228/310 nm in acetonitrile-water solution (v:v, 40:60). The analysis of the unknown samples showed that ic-ELISA agreed well with the HPLC results. It also revealed that the ELISA developed here could be a useful tool for screening BPA in children's sera before the validation of HPLC. PMID- 26888527 TI - Comprehensive analysis of PM10 in Belgrade urban area on the basis of long-term measurements. AB - In this study, we investigated the impact of potential emission sources and transport pathways on annual and seasonal PM10 loadings in an urban area of Belgrade (Serbia). The analyzed dataset comprised PM10 mass concentrations for the period 2003-2015, as well as their chemical composition (organic/elemental carbon, benzo[a]pyrene, As, Cd, Cr, Mn, Ni, Pb, Cl(-), Na(+), Mg(2+), Ca(2+), K(+), NO3 (-), SO4 (2-), and NH4 (+)), meteorological parameters, and concentrations of inorganic gaseous pollutants and soot for the period 2011-2015. The combination of different methods, such as source apportionment (Unmix), ensemble learning method (random forest), and multifractal and inverse multifractal analysis, was utilized in order to obtain a detailed description of the PM10 origin and spatio-temporal distribution and to determine their relationship with other pollutants and meteorological parameters. The contribution of long-range and regional transport was estimated by means of trajectory sector analysis, whereas the hybrid receptor models were applied to identify potential areas of concern. PMID- 26888528 TI - Bacteria-based polythene degradation products: GC-MS analysis and toxicity testing. AB - Polythene degradation leads to the production of various by-products depending upon the type of degradation process. The polythene degradation products (PEDP) in the culture supernatant of the two bacteria (Lysinibacillus fusiformis strain VASB14/WL and Bacillus cereus strain VASB1/TS) were analyzed with GC-MS technique. The major by-products in the PEDP in the culture supernatant of L. fusiformis strain VASB14/WL (1,2,3,4 tetra methyl benzene) and B. cereus strain VASB1/TS (1,2,3 trimethyl benzene, 1 ethyl 3,5-dimethyl benzene, 1,4 di methyl 2 ethyl benzene, and dibutyl phthalate) dissolved in diethyl ether were recorded. To assess the environmental applicability of polythene degradation using L. fusiformis strain VASB14/WL and B. cereus strain VASB1/TS at in vitro level. The effect of PEDP produced after 2 months of regular shaking at room temperature on both plants and animal system was studied. No significant decrease in the percent seed germination was recorded with the PEDP of both the bacteria. PEDP produced by L. fusiformis strain VASB14/WL did not report any significant change in germination index (GI) at 10 and 25 %, but least GI (39.66 +/- 13.94) was documented at 50 % concentration of PEDP. Highest elongation inhibition rate (53.83 +/- 15.71) of Sorghum was also recorded with L. fusiformis and at the same concentration. PMID- 26888529 TI - Effects of 4-methylbenzylidene camphor (4-MBC) on neuronal and muscular development in zebrafish (Danio rerio) embryos. AB - The negative effects of overexposure to ultraviolet (UV) radiation in humans, including sunburn and light-induced cellular injury, are of increasing public concern. 4-Methylbenzylidene camphor (4-MBC), an organic chemical UV filter, is an active ingredient in sunscreen products. To date, little information is available about its neurotoxicity during early vertebrate development. Zebrafish embryos were exposed to various concentrations of 4-MBC in embryo medium for 3 days. In this study, a high concentration of 4-MBC, which is not being expected at the current environmental concentrations in the environment, was used for the purpose of phenotypic screening. Embryos exposed to 15 MUM of 4-MBC displayed abnormal axial curvature and exhibited impaired motility. Exposure effects were found to be greatest during the segmentation period, when somite formation and innervation occur. Immunostaining of the muscle and axon markers F59, znp1, and zn5 revealed that 4-MBC exposure leads to a disorganized pattern of slow muscle fibers and axon pathfinding errors during the innervation of both primary and secondary motor neurons. Our results also showed reduction in AChE activity upon 4-MBC exposure both in vivo in the embryos (15 MUM) and in vitro in mammalian Neuro-2A cells (0.1 MUM), providing a possible mechanism for 4-MBC-induced muscular and neuronal defects. Taken together, our results have shown that 4-MBC is a teratogen and influences muscular and neuronal development, which may result in developmental defects. PMID- 26888530 TI - The unphosphorylated form of the PilR two-component system regulates pilA gene expression in Geobacter sulfurreducens. AB - In Geobacter sulfurreducens, metal reduction and generation of bioelectricity require the participation of several elements, and among them, the type IV pili has an essential role. The pilus is composed of multiple PilA monomers. Expression of pilA gene depends mainly on the sigma54 factor and the response regulator protein PilR. In this work, we characterized the role of the PilS-PilR two-component system in the regulation of the pilA gene expression. Experimental evidence indicates that PilS is autophosphorylated at the His-334 residue, which in turn is transferred to the conserved Asp-53 in PilR. Contrary to other PilS PilR systems, substitution D53N in PilR resulted in higher activation of the pilA gene. By using a pilA::luxCDABE fusion with different promoter fragments and in vitro DNA-binding assays, we demonstrated the existence of multiple functional PilR binding sites. A regulatory model in which the non-phosphorylated PilR protein directs activation of pilA expression by binding to two sites in the promoter region of this gene is presented. PMID- 26888531 TI - Effect of carbon to nitrogen ratio of feed wastewater and sludge retention time on activated sludge in a submerged membrane bioreactor. AB - This paper investigated the effects of extracellular polymeric substances (EPS) on the activated sludge rheology in a submerged membrane bioreactor (sMBR) operated at different sludge retention time (SRT) values and different carbon to nitrogen ratios (C/N) of feed wastewater. The C/N ratios of the feed were adjusted accordingly so that synthetic wastewaters prepared simulated municipal wastewater, non-toxic wastewater with high C/N ratio and non-toxic wastewater with low C/N ratio. A number of important operational parameters such as mixed liquor suspended solid (MLSS), protein fraction of EPS (EPSp), carbohydrate fraction of EPS (EPSc), protein fraction of soluble microbial product (SMPp), carbohydrate fraction of SMP (SMPc), apparent viscosity, critical flux and hydrophobicity in mixed liquor and their correlations were investigated in the sMBR systems operated. The statistical analysis indicated that the C/N ratio of feed, SRT, MLSS and SMPc were found to have positive effects on apparent viscosity at three different shear rates. On the other hand, a negative impact was detected between the apparent viscosities and the critical fluxes. It was also observed that there is a significant positive correlation between hydrophobicity and both EPSp and SMPp. PMID- 26888533 TI - Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes. AB - BACKGROUND AND PURPOSE: Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. METHODS: We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: A total of 100 patients were included in the final analysis (mean age, 63.5+/-14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2+/-8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score <=2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. CONCLUSIONS: Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization. PMID- 26888534 TI - Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta Analysis. AB - BACKGROUND AND PURPOSE: Silent brain infarction (SBI) on magnetic resonance imaging has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between magnetic resonance imaging-defined SBI and future stroke risk. METHODS: We searched the medical literature to identify cohort studies involving adults with SBI detected by magnetic resonance imaging who were subsequently followed up for incident clinically defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between magnetic resonance imaging-detected SBI and future symptomatic stroke was measured by an hazard ratio. RESULTS: The meta-analysis included 13 studies (14 764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% confidence interval, 2.24-3.86, P<0.001; Q=39.65, P<0.001). In the 8 studies of 10 427 subjects providing hazard ratio adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (hazard ratio, 2.08 [95% confidence interval, 1.69-2.56; P<0.001]; Q=8.99; P=0.25). In a subgroup analysis pooling 9483 stroke-free individuals from large population-based studies, SBI was present in ~18% of participants and remained a strong predictor of future stroke (hazard ratio, 2.06 [95% confidence interval, 1.64-2.59]; P<0.01). CONCLUSIONS: SBI is present in ~1 in 5 stroke-free older adults and is associated with a 2 fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions. PMID- 26888532 TI - Safety and Efficacy of Solitaire Stent Thrombectomy: Individual Patient Data Meta Analysis of Randomized Trials. AB - BACKGROUND AND PURPOSE: Recent positive randomized trials of endovascular therapy for ischemic stroke used predominantly stent retrievers. We pooled data to investigate the efficacy and safety of stent thrombectomy using the Solitaire device in anterior circulation ischemic stroke. METHODS: Patient-level data were pooled from trials in which the Solitaire was the only or the predominant device used in a prespecified meta-analysis (SEER Collaboration): Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment (SWIFT PRIME), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND IA), and Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT). The primary outcome was ordinal analysis of modified Rankin Score at 90 days. The primary analysis included all patients in the 4 trials with 2 sensitivity analyses: (1) excluding patients in whom Solitaire was not the first device used and (2) including the 3 Solitaire-only trials (excluding ESCAPE). Secondary outcomes included functional independence (modified Rankin Score 0-2), symptomatic intracerebral hemorrhage, and mortality. RESULTS: The primary analysis included 787 patients: 401 randomized to endovascular thrombectomy and 386 to standard care, and 82.6% received intravenous thrombolysis. The common odds ratio for modified Rankin Score improvement was 2.7 (2.0-3.5) with no heterogeneity in effect by age, sex, baseline stroke severity, extent of computed tomography changes, site of occlusion, or pretreatment with alteplase. The number needed to treat to reduce disability was 2.5 and for an extra patient to achieve independent outcome was 4.25 (3.29-5.99). Successful revascularization occurred in 77% treated with Solitaire device. The rate of symptomatic intracerebral hemorrhage and overall mortality did not differ between treatment groups. CONCLUSIONS: Solitaire thrombectomy for large vessel ischemic stroke was safe and highly effective with substantially reduced disability. Benefits were consistent in all prespecified subgroups. PMID- 26888535 TI - Inflammatory Markers and Outcomes After Lacunar Stroke: Levels of Inflammatory Markers in Treatment of Stroke Study. AB - BACKGROUND AND PURPOSE: We hypothesized that concentrations of interleukin 6 (IL 6), serum amyloid A, tumor necrosis factor-alpha receptor 1, CD40 ligand, and monocyte chemoattractant protein 1 would predict recurrent ischemic stroke and major vascular events after recent lacunar stroke. METHODS: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes (SPS3) study, a Phase III trial in patients with recent lacunar stroke. Crude and Adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for recurrence risks. RESULTS: Among 1244 patients with lacunar stroke (mean age, 63.3+/-10.8 years), there were 115 major vascular events (stroke, myocardial infarction, and vascular death). The risk of major vascular events increased with elevated concentrations of both tumor necrosis factor-alpha receptor 1 (adjusted HR per SD, 1.21; 95% CI, 1.05-1.41; P=0.01) and IL-6 (adjusted HR per SD, 1.10; 95% CI, 1.02-1.19; P=0.008). Compared with the bottom quartile (tumor necrosis factor-alpha receptor 1 <2.24 ng/L), those in the top quartile of tumor necrosis factor-alpha receptor 1 (>3.63 ng/L) were at twice the risk of major vascular events after adjusting for demographics (partially adjusted HR, 1.98; 95% CI, 1.11-3.52), though the effect attenuated after adjusting for other risk factors and statin use (adjusted HR, 1.68; 95% CI, 0.93 3.04). Serum amyloid A, CD40 ligand, and monocyte chemoattractant protein 1 were not associated with prognosis. CONCLUSIONS: Among recent lacunar stroke patients, IL-6 and TNF receptor concentrations predict risk of recurrent vascular events, and they are associated with the effect of antiplatelet therapies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306. PMID- 26888536 TI - Pediatric Cortical Vein Thrombosis: Frequency and Association With Venous Infarction. AB - BACKGROUND AND PURPOSE: Cortical vein thrombosis (CVT) is an uncommon site of involvement in cerebral sinovenous thrombosis. Few reports have described pediatric CVT, and none has differentiated its unique attributes. This study assessed the clinical features and radiographic outcome of a cohort of children with cerebral sinovenous thrombosis, comparing those with CVT to those without CVT. METHODS: Children diagnosed with cerebral sinovenous thrombosis were retrospectively reviewed and separated into 2 groups based on the presence or absence of cortical vein involvement. RESULTS: Fifty patients met inclusion criteria, including 12 with CVT. The CVT group was more likely to present with seizure (P=0.0271), altered mental status (P=0.0271), and a family history of clotting disorder (P=0.0477). Acute imaging of the CVT group more commonly demonstrated concurrent superior sagittal sinus thrombosis (P=0.0024), parenchymal hemorrhage (P=0.0141), and restricted diffusion (P<0.0001). At follow up, the CVT group more commonly showed headache, seizure, and focal neurological deficit (P=0.0449), and venous infarction (P=0.0007). CONCLUSIONS: In our cohort, CVT was significantly associated with seizures at presentation, hemorrhage and restricted diffusion on acute imaging, as well as neurological disability and venous infarction at follow-up. Involvement of cortical veins in cerebral sinovenous thrombosis is associated with an increased risk of infarction and adverse outcome in children. PMID- 26888538 TI - The alcohol harm paradox: using a national survey to explore how alcohol may disproportionately impact health in deprived individuals. AB - BACKGROUND: Internationally, studies show that similar levels of alcohol consumption in deprived communities (vs. more affluent) result in higher levels of alcohol-related ill health. Hypotheses to explain this alcohol harm paradox include deprived drinkers: suffering greater combined health challenges (e.g. smoking, obesity) which exacerbate effects of alcohol harms; exhibiting more harmful consumption patterns (e.g. bingeing); having a history of more harmful consumption; and disproportionately under-reporting consumption. We use a bespoke national survey to assess each of these hypotheses. METHODS: A national telephone survey designed to test this alcohol harm paradox was undertaken (May 2013 to April 2014) with English adults (n = 6015). Deprivation was assigned by area of residence. Questions examined factors including: current and historic drinking patterns; combined health challenges (smoking, diet, exercise and body mass); and under-reported consumption (enhanced questioning on atypical/special occasion drinking). For each factor, analyses examined differences between deprived and more affluent individuals controlled for total alcohol consumption. RESULTS: Independent of total consumption, deprived drinkers were more likely to smoke, be overweight and report poor diet and exercise. Consequently, deprived increased risk drinkers (male >168-400 g, female >112-280 g alcohol/week) were >10 times more likely than non-deprived counterparts to drink in a behavioural syndrome combining smoking, excess weight and poor diet/exercise. Differences by deprivation were significant but less marked in higher risk drinkers (male >400 g, female >280 g alcohol/week). Current binge drinking was associated with deprivation independently of total consumption and a history of bingeing was also associated with deprivation in lower and increased risk drinkers. CONCLUSIONS: Deprived increased/higher drinkers are more likely than affluent counterparts to consume alcohol as part of a suite of health challenging behaviours including smoking, excess weight and poor diet/exercise. Together these can have multiplicative effects on risks of wholly (e.g. alcoholic liver disease) and partly (e.g. cancers) alcohol-related conditions. More binge drinking in deprived individuals will also increase risks of injury and heart disease despite total alcohol consumption not differing from affluent counterparts. Public health messages on how smoking, poor diet/exercise and bingeing escalate health risks associated with alcohol are needed, especially in deprived communities, as their absence will contribute to health inequalities. PMID- 26888541 TI - Proton pump inhibitors may be linked to dementia risk. PMID- 26888539 TI - Daptomycin > 6 mg/kg/day as salvage therapy in patients with complex bone and joint infection: cohort study in a regional reference center. AB - BACKGROUND: Even if daptomycin does not have approval for the treatment of bone and joint infections (BJI), the Infectious Diseases Society of America guidelines propose this antibiotic as alternative therapy for prosthetic joint infection. The recommended dose is 6 mg/kg/d, whereas recent data support the use of higher doses in these patients. METHODS: We performed a cohort study including consecutive patients that have received daptomycin >6 mg/kg/d for complex BJI between 2011 and 2013 in a French regional reference center. Factors associated with treatment failure were determined on univariate Cox analysis and Kaplan Meier curves. RESULTS: Forty-three patients (age, 61 +/- 17 years) received a mean dose of 8 +/- 0.9 mg/kg/d daptomycin, for a mean 81 +/- 59 days (range, 6 303 days). Most had chronic (n = 37, 86 %) implant-associated (n = 37, 86 %) BJI caused by coagulase-negative staphylococci (n = 32, 74 %). A severe adverse event (SAE) occurred in 6 patients (14 %), including 2 cases of eosinophilic pneumonia, concomitant with daptomycin Cmin >24 mg/L. Outcome was favorable in 30 (77 %) of the 39 clinically assessable patients. Predictors for treatment failure were age, non-optimal surgery and daptomycin withdrawal for SAE. CONCLUSIONS: Prolonged high-dose daptomycin therapy was effective in patients with complex BJI. However, optimal surgery remains the cornerstone of medico-surgical strategy; and a higher incidence of eosinophilic pneumonia than expected was recorded. PMID- 26888540 TI - Sixty seconds on . . . bed blockers. PMID- 26888542 TI - "I Feel Lucky" - Gratitude Among Young Adults with Phenylketonuria (PKU). AB - If persons with phenylketonuria (PKU) do not start a protein restricted diet in early infancy, they will suffer severe brain damage. Previous qualitative research on adults and adolescents with PKU has identified stigmatization, uncertain risk perceptions, considerable time spent on preparing food, and incongruence between the PKU diet and certain lifestyle demands. The aim of this study was to explore young and early treated Norwegian adults' experiences, by conducting in-depth interviews in 2011 with 11 adults with PKU, aged 20-30. Being the first qualitative study on people with PKU in Norway, the process was inspired by grounded theory. All participants reflected on their own health and existence by expressing positive counterfactual thoughts. They considered themselves lucky to have had parents who had managed the diet, they were grateful for the time and place they were born, and for information and treatment availability, although the results also show some ambiguous attitudes towards the hospital which provided the treatment. The expression of gratitude in association with having PKU suggests a major positive coping strategy. It contributes to a more holistic understanding of the experiences and attitudes of young, Norwegian adults with PKU, as it provides a counterweight to the negative experiences. PMID- 26888543 TI - Nanofiber scaffolds influence organelle structure and function in bone marrow stromal cells. AB - Recent work demonstrates that osteoprogenitor cell culture on nanofiber scaffolds can promote differentiation. This response may be driven by changes in cell morphology caused by the three-dimensional (3D) structure of nanofibers. We hypothesized that nanofiber effects on cell behavior may be mediated by changes in organelle structure and function. To test this hypothesis, human bone marrow stromal cells (hBMSCs) were cultured on poly(epsilon-caprolactone) (PCL) nanofibers scaffolds and on PCL flat spuncoat films. After 1 day-culture, hBMSCs were stained for actin, nucleus, mitochondria, and peroxisomes, and then imaged using 3D confocal microscopy. Imaging revealed that the hBMSC cell body (actin) and peroxisomal volume were reduced during culture on nanofibers. In addition, the nucleus and peroxisomes occupied a larger fraction of cell volume during culture on nanofibers than on films, suggesting enhancement of the nuclear and peroxisomal functional capacity. Organelles adopted morphologies with greater 3D character on nanofibers, where the Z-Depth (a measure of cell thickness) was increased. Comparisons of organelle positions indicated that the nucleus, mitochondria, and peroxisomes were closer to the cell center (actin) for nanofibers, suggesting that nanofiber culture induced active organelle positioning. The smaller cell volume and more centralized organelle positioning would reduce the energy cost of inter-organelle vesicular transport during culture on nanofibers. Finally, hBMSC bioassay measurements (DNA, peroxidase, bioreductive potential, lactate, and adenosine triphosphate (ATP)) indicated that peroxidase activity may be enhanced during nanofiber culture. These results demonstrate that culture of hBMSCs on nanofibers caused changes in organelle structure and positioning, which may affect organelle functional capacity and transport. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. J Biomed Mater Res Part B: Appl Biomater, 2016. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 989 1001, 2017. PMID- 26888544 TI - Epidemic activity of respiratory syncytial virus is related to temperature and rainfall in equatorial tropical countries. AB - Although viral acute lower respiratory infections (ALRIs) are a major public health problem in tropical low- and middle-income countries (LMICs), and there is growing evidence showing their relationship with meteorological parameters, studies performed in these countries are scarce. In an analytical cross-sectional study, we determined which of the main meteorological parameters (temperature, absolute humidity, rainfall, wind speed, and solar radiation) predicted respiratory syncytial virus (RSV) activity in a population of hospitalized children with ALRI during a 5-year period, from January 2009 to December 2013. Out of a total of 4559 children included in the study (mean age 9.2 +/- 8.5 months), 2953 (64.8%) presented RSV infection during the 3-month period from March to May. In the multivariate analysis, after controlling for absolute humidity, wind speed, and solar radiation, temperature [incidence rate ratio (IRR) 2.25, 95% confidence interval (CI) 1.11-4.53, P = 0.024], and rainfall (IRR 1.01, 95% CI 1.00-1.02, P = 0.044) were independently associated with the monthly number of RSV infections. In conclusion, in Bogota, the capital of a tropical LMIC lying slightly above the equator, RSV activity peaks in the 3-month period from March to May, the main rainy period of the year in the city. In addition, rainfall and temperature are the two most important meteorological parameters that are independently associated with RSV activity in hospitalized children with ALRI in the city. PMID- 26888537 TI - Transmission-blocking strategies: the roadmap from laboratory bench to the community. AB - Malaria remains one of the most prevalent tropical and infectious diseases in the world, with an estimated more than 200 million clinical cases every year. In recent years, the mosquito stages of the parasite life cycle have received renewed attention with some progress being made in the development of transmission-blocking strategies. From gametocytes to late ookinetes, some attractive antigenic targets have been found and tested in order to develop a transmission blocking vaccine, and drugs are being currently screened for gametocytocidal activity, and also some new and less conventional approaches are drawing increased attention, such as genetically modified and fungus-infected mosquitoes that become refractory to Plasmodium infection. In this review some of those strategies focusing on the progress made so far will be summarized, but also, the challenges that come from the translation of early promising benchwork resulting in successful applications in the field. To do this, the available literature will be screened and all the pieces of the puzzle must be combined: from molecular biology to epidemiologic and clinical data. PMID- 26888545 TI - Pollinator-prey conflicts in carnivorous plants: When flower and trap properties mean life or death. AB - Insect-pollinated carnivorous plants are expected to have higher fitness if they resolve pollinator-prey conflicts by sparing insects pollinating their flowers while trapping prey insects. We examined whether separation between flowers and traps of the carnivorous sundew species or pollinator preferences for colours of flowers enable these plants to spare pollinators. In addition, we collected odours from flowers and traps of each carnivorous species in order to identify volatile chemicals that are attractive or repellent to pollinators and prey insects. In Drosera spatulata and D. arcturi, no volatiles were detected from either their flowers or traps that could serve as kairomone attractants for insects. However, behavioural experiments indicated white colour and spatial separation between flowers and traps aid in reducing pollinator entrapment while capturing prey. In contrast, D. auriculata have flowers that are adjacent to their traps. In this species we identified chemical signals emanating from flowers that comprised an eight-component blend, while the plant's traps emitted a unique four-component blend. The floral odour attracted both pollinator and prey insects, while trap odour only attracted prey. This is the first scientific report to demonstrate that carnivorous plants utilize visual, spatial, and chemical signals to spare flower visitors while trapping prey insects. PMID- 26888546 TI - Vocational rehabilitation case manager factors associated with vocational rehabilitation service program outcomes for people with disabilities in Taiwan - an exploratory study. AB - Purpose The aim of this study is to explore whether/which vocational rehabilitation case manager (VRCMer) factors were significantly associated with the vocational rehabilitation service (VRS) program outcomes in Taiwan. Method This study used the 2011 VRS Program for People with Disabilities Database in a metropolitan city in Taiwan (N = 466) to do a secondary data analysis using hierarchical logistic regression. Results This study found that the employment rate and stable employment rate created by the 2011 VRS program in a metropolitan city in Taiwan were 48.7% and 42.1%, respectively. For the predictors of employment/stable employment, "occurrences of the services provided by the VRCMer" variable was definitely dominant. In addition, "level of the disability" was the second-ranking predictor, and was significantly negatively correlated with both employment and stable employment outcomes. Conclusions Vocational rehabilitation case manager factors in this study were significantly correlated with VRS program outcomes for people with disabilities in Taiwan after controlling for the clients' socio-demographic variables. The results indicate that greater input by VRCMers for people with disabilities equates to better employment outcomes in metropolitan Taiwan. Implications for Rehabilitation This is the first study to build an inferential statistical model in attempt to explain and predict the association between vocational rehabilitation case manager factors and vocational rehabilitation service program outcomes for people with disabilities in Taiwan. In cases of severe disability, a vocational rehabilitation case manager should seek out more in-kind and in-cash resources, and choose a suitable job coach to cooperate in assisting the client to become employed. Based on the findings, government has to continue implementing opportunities for people with disabilities to attain higher and better quality educational levels, for increasing their employment rate. Vocational rehabilitation case managers should raise the referral rate and cooperation with job coaches as this directly affects the quality of services and clients' employment rate. PMID- 26888547 TI - The use of ayurvedic medicine in the context of health promotion--a mixed methods case study of an ayurvedic centre in Sweden. AB - BACKGROUND: Ayurveda has its historical roots in India, but has also been internationalised, partly via migration and partly through an increased interest in alternative medicine in the West, where studies point toward increased use. However, there is to date scarce knowledge about the use and experiences of ayurveda in Sweden. METHODS: We have conducted a case study of a center for ayurvedic healthcare in Sweden. We have collected information on client background data from the center's documentation, and compiled data from all clients who visited the centre for ayurvedic consultation during spring 2014. In total, 55 individuals were included in the study, and 18 of them were chosen for individual semi-structured interviews, to gain a deeper understanding of their motives for seeking, and experiences of ayurvedic health care. The material was analysed and compiled through a mix of qualitative and quantitative methods. RESULTS: Among the 55 clients, 91% were female the mean age was 47 years, and 64% gave a specific illness as a reason for seeking ayurveda. The most common illnesses were respiratory, musculoskeletal, circulatory, tumor, and cutaneous illnesses. The qualitative results showed that ayurveda was being used in combination with other methods, including various diets, other alternative medicine methods and conventional medicine. Some participants recounted having sought ayurveda as a complement to conventional medicine, or in cases when conventional medicine had been experienced as insufficient in terms of diagnosis or treatment. However, some participants experienced it as difficult to follow the ayurvedic life-style advice in the midst of their everyday life. Many participants reported positive experiences of pulse diagnostics, which was the main diagnostic method used in ayurvedic consultation. Some reported concrete, physical improvement of their symptoms. CONCLUSIONS: This study points towards important aspects of participant experience of ayurveda, that may be subject to further research. The positive effects experienced by some clients should be studied more systematically in order to discern whether they are specific or non specific. In addition, interesting knowledge may be gained through further study of the reported positive experiences of pulse diagnosis. PMID- 26888548 TI - Giocampus school: a "learning through playing" approach to deliver nutritional education to children. AB - To improve nutritional knowledge of children, single-group educational interventions with pre/post knowledge assessment were performed in primary schools in Parma, Italy, participating to the Giocampus Program. A total of 8165 children (8-11 years old) of 3rd, 4th and 5th grades of primary school were involved in 3 hours per class nutritional lessons, with specifically designed games and activities for each school grade. To evaluate children learning, a questionnaire was administered before and after three months of educational intervention. A total of 16330 questionnaires were analysed. Children nutritional knowledge significantly increased (p< 0.001) in all school grades. The integrated "learning through playing" approach, including the educational figures, tools and games, was successful in improving children's nutritional knowledge. A stable integration of this method in primary school settings could prepare a new generation of citizens, better educated on health-promotion lifestyles. PMID- 26888549 TI - High-resolution dynamic CE-MRA of the thorax enabled by iterative TWIST reconstruction. AB - PURPOSE: To evaluate the clinical benefit of using a new iterative reconstruction technique fully integrated on a standard clinical scanner and reconstruction system using a TWIST acquisition for high-resolution dynamic three-dimensional contrast-enhanced MR angiography (CE-MRA). METHODS: Low-dose, high-resolution TWIST datasets of 11 patients were reconstructed using both standard GRAPPA-based reconstruction for reference and iterative reconstruction, which reduces the temporal footprint of reconstructed images. Image quality of both techniques was assessed by two experienced readers, as well as quantitatively evaluated using a time-signal curve analysis. RESULTS: Image quality scores consistently and significantly improved by using iterative reconstruction compared with the standard approach. Most notably, the delineation of small to mid-size vasculature improved from a mean Likert score between "nondiagnostic" and "poor" for standard to between "good" and "excellent" for iterative reconstruction. The full width at half maximum of the contrast agent bolus computed from the time-signal curve was also reduced by iterative reconstruction, allowing for more precise bolus timing. CONCLUSION: Iterative reconstruction can substantially improve high-resolution dynamic CE-MRA image quality, most notably in small to mid-size vasculature. Dynamic CE-MRA with iterative reconstruction could become an alternative to conventional static 3D CE-MRA, thus simplifying the clinical workflow. Magn Reson Med 77:833-840, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26888550 TI - Erratum to: signatures of early frailty in the gut microbiota. PMID- 26888551 TI - Rater reliability and scoring duration of the Quality Function Measure in ambulant children with hyperkinetic movement disorders. AB - AIM: To examine intra- and interrater reliability/agreement, and time taken to score, when the Quality Function Measure (QFM) is applied to children with hyperkinetic movement disorders (HMD; e.g. dystonia, chorea, athetosis, tremor, and myoclonus). METHOD: Fifteen ambulant children with HMD participated (eight males, seven females; mean age 13y 7mo, SD 3y 7mo). Three trained raters (two physiotherapists, one occupational therapist) independently scored the QFM using videos of each child performing Gross Motor Function Measure (GMFM) Stand and Walk/Run/Jump dimensions. Reliability was evaluated using intraclass correlation coefficient (ICC) model 2.1, Standard Error of Measurement (SEM), and Bland Altman methods. RESULTS: Rater reliability was excellent for all five QFM attributes: intrarater ICCs >=0.98 (95% confidence interval [CI] 0.83-1.00), and interrater ICCs >=0.96 (95% CI 0.91-1.00). SEM varied from 2.07% to 4.72% points for intra- and interrater scores across QFM attributes. Bland-Altman tests demonstrated close agreement between ratings, with absolute mean differences varying from 0.34% to 3.23% (intrarater) to 1.67% to 3.82% (interrater). Median scoring duration time was 83 minutes (range 56-144min, SD 16.02). INTERPRETATION: Low measurement error attributable to rater effects suggests the QFM has potential as an evaluative measure in research studies involving children with HMD, though its lengthy scoring requirements are an important consideration for clinical practice. Evaluation of test-retest reliability and responsiveness is required. PMID- 26888552 TI - Biotic and environmental dynamics through the Late Jurassic-Early Cretaceous transition: evidence for protracted faunal and ecological turnover. AB - The Late Jurassic to Early Cretaceous interval represents a time of environmental upheaval and cataclysmic events, combined with disruptions to terrestrial and marine ecosystems. Historically, the Jurassic/Cretaceous (J/K) boundary was classified as one of eight mass extinctions. However, more recent research has largely overturned this view, revealing a much more complex pattern of biotic and abiotic dynamics than has previously been appreciated. Here, we present a synthesis of our current knowledge of Late Jurassic-Early Cretaceous events, focusing particularly on events closest to the J/K boundary. We find evidence for a combination of short-term catastrophic events, large-scale tectonic processes and environmental perturbations, and major clade interactions that led to a seemingly dramatic faunal and ecological turnover in both the marine and terrestrial realms. This is coupled with a great reduction in global biodiversity which might in part be explained by poor sampling. Very few groups appear to have been entirely resilient to this J/K boundary 'event', which hints at a 'cascade model' of ecosystem changes driving faunal dynamics. Within terrestrial ecosystems, larger, more-specialised organisms, such as saurischian dinosaurs, appear to have suffered the most. Medium-sized tetanuran theropods declined, and were replaced by larger-bodied groups, and basal eusauropods were replaced by neosauropod faunas. The ascent of paravian theropods is emphasised by escalated competition with contemporary pterosaur groups, culminating in the explosive radiation of birds, although the timing of this is obfuscated by biases in sampling. Smaller, more ecologically diverse terrestrial non-archosaurs, such as lissamphibians and mammaliaforms, were comparatively resilient to extinctions, instead documenting the origination of many extant groups around the J/K boundary. In the marine realm, extinctions were focused on low-latitude, shallow marine shelf-dwelling faunas, corresponding to a significant eustatic sea-level fall in the latest Jurassic. More mobile and ecologically plastic marine groups, such as ichthyosaurs, survived the boundary relatively unscathed. High rates of extinction and turnover in other macropredaceous marine groups, including plesiosaurs, are accompanied by the origin of most major lineages of extant sharks. Groups which occupied both marine and terrestrial ecosystems, including crocodylomorphs, document a selective extinction in shallow marine forms, whereas turtles appear to have diversified. These patterns suggest that different extinction selectivity and ecological processes were operating between marine and terrestrial ecosystems, which were ultimately important in determining the fates of many key groups, as well as the origins of many major extant lineages. We identify a series of potential abiotic candidates for driving these patterns, including multiple bolide impacts, several episodes of flood basalt eruptions, dramatic climate change, and major disruptions to oceanic systems. The J/K transition therefore, although not a mass extinction, represents an important transitional period in the co-evolutionary history of life on Earth. PMID- 26888553 TI - Implementation and Clinical Outcomes of an Employer-Sponsored, Pharmacist Provided Medication Therapy Management Program--Alternative Viewpoint. PMID- 26888555 TI - Rheumatoid arthritis: Could glucose metabolism be a sweet target for RA therapy? PMID- 26888556 TI - Shedding light on an ultra-bright photoluminescent lamellar gold thiolate coordination polymer [Au(p-SPhCO2Me)]n. AB - The first structure elucidation of a lamellar gold thiolate coordination polymer is described. [Au(p-SPhCO2Me)]n is obtained from the simultaneous esterification of mercaptobenzoic acid and reduction of the Au(iii) precursor. Despite the presence of aurophilic interactions, the intense phosphorescence (QY ~ 70%) originates from intra-ligand and metal-to-ligand transitions. PMID- 26888554 TI - The BAFFling effects of rituximab in lupus: danger ahead? AB - Suboptimal trial design and concurrent therapies are thought to account for the unexpected failure of two clinical trials of rituximab in patients with systemic lupus erythematosus (SLE). However, in this Opinion article we propose an alternative explanation: that rituximab can trigger a sequence of events that exacerbates disease in some patients with SLE. Post-rituximab SLE flares that are characterized by high levels of antibodies to double-stranded DNA are associated with elevated circulating BAFF (B-cell-activating factor, also known as TNF ligand superfamily member 13B or BLyS) levels, and a high proportion of plasmablasts within the B-cell pool. BAFF not only perpetuates autoreactive B cells (including plasmablasts), particularly when B-cell numbers are low, but also stimulates T follicular helper (TFH) cells. Moreover, plasmablasts and TFH cells promote each others' formation. Thus, repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of disease. We argue that B-cell depletion should be swiftly followed by BAFF inhibition in patients with SLE. PMID- 26888557 TI - Evaluation of a wireless activity monitoring system to quantify locomotor activity in horses in experimental settings. AB - REASONS FOR PERFORMING STUDY: Methods of evaluating locomotor activity can be useful in efforts to quantify behavioural activity in horses objectively. OBJECTIVES: To evaluate whether an accelerometric device would be adequate to quantify locomotor activity and step frequency in horses, and to distinguish between different levels of activity and different gaits. STUDY DESIGN: Observational study in an experimental setting. METHODS: Dual-mode (activity and step count) piezo-electric accelerometric devices were placed at each of 4 locations (head, withers, forelimb and hindlimb) in each of 6 horses performing different controlled activities including grazing, walking at different speeds, trotting and cantering. Both the activity count and step count were recorded and compared by the various activities. Statistical analyses included analysis of variance for repeated measures, receiver operating characteristic curves, Bland Altman analysis and linear regression. RESULTS: The accelerometric device was able to quantify locomotor activity at each of the 4 locations investigated and to distinguish between gaits and speeds. The activity count recorded by the accelerometer placed on the hindlimb was the most accurate, displaying a clear discrimination between the different levels of activity and a linear correlation to speed. The accelerometer placed on the head was the only one to distinguish specifically grazing behaviour from standing. The accelerometer placed on the withers was unable to differentiate different gaits and activity levels. The step count function measured at the hindlimb was reliable but the count was doubled at the walk. CONCLUSIONS: The dual-mode accelerometric device was sufficiently accurate to quantify and compare locomotor activity in horses moving at different speeds and gaits. Positioning the device on the hindlimb allowed for the most accurate results. The step count function can be useful but must be manually corrected, especially at the walk. PMID- 26888558 TI - Apical versus Non-Apical Lead: Is ICD Lead Position Important for Successful Defibrillation? AB - INTRODUCTION: We aim to compare the acute and long-term success of defibrillation between non-apical and apical ICD lead position. METHODS AND RESULTS: The position of the ventricular lead was recorded by the implanting physician for 2,475 of 2,500 subjects in the Shockless IMPLant Evaluation (SIMPLE) trial, and subjects were grouped accordingly as non-apical or apical. The success of intra operative defibrillation testing and of subsequent clinical shocks were compared. Propensity scoring was used to adjust for the impact of differences in baseline variables between these groups. There were 541 leads that were implanted at a non apical position (21.9%). Patients implanted with a non-apical lead had a higher rate of secondary prevention indication. Non-apical location resulted in a lower mean R-wave amplitude (14.0 vs. 15.2, P < 0.001), lower mean pacing impedance (662 ohm vs. 728 ohm, P < 0.001), and higher mean pacing threshold (0.70 V vs. 0.66 V, P = 0.01). Single-coil leads and cardiac resynchronization devices were used more often in non-apical implants. The success of intra-operative defibrillation was similar between propensity score matched groups (89%). Over a mean follow-up of 3 years, there were no significant differences in the yearly rates of appropriate shock (5.5% vs. 5.4%, P = 0.98), failed appropriate first shock (0.9% vs. 1.0%, P = 0.66), or the composite of failed shock or arrhythmic death (2.8% vs. 2.3% P = 0.35) according to lead location. CONCLUSION: We did not detect any reduction in the ICD efficacy at the time of implant or during follow up in patients receiving a non-apical RV lead. PMID- 26888559 TI - Emerging importance of chemokine receptor CXCR3 and its ligands in cardiovascular diseases. AB - The CXC chemokines, CXCL4, -9, -10, -11, CXCL4L1, and the CC chemokine CCL21, activate CXC chemokine receptor 3 (CXCR3), a cell-surface G protein-coupled receptor expressed mainly by Th1 cells, cytotoxic T (Tc) cells and NK cells that have a key role in immunity and inflammation. However, CXCR3 is also expressed by vascular smooth muscle and endothelial cells, and appears to be important in controlling physiological vascular function. In the last decade, evidence from pre-clinical and clinical studies has revealed the participation of CXCR3 and its ligands in multiple cardiovascular diseases (CVDs) of different aetiologies including atherosclerosis, hypertension, cardiac hypertrophy and heart failure, as well as in heart transplant rejection and transplant coronary artery disease (CAD). CXCR3 ligands have also proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodelling. The observation that several of the above-mentioned chemokines exert biological actions independent of CXCR3 provides both opportunities and challenges for developing effective drug strategies. In this review, we provide evidence to support our contention that CXCR3 and its ligands actively participate in the development and progression of CVDs, and may additionally have utility as diagnostic and prognostic biomarkers. PMID- 26888561 TI - Does high-density lipoprotein protect vascular function in healthy pregnancy? AB - The maternal adaptation to pregnancy includes hyperlipidaemia, oxidative stress and chronic inflammation. In non-pregnant individuals, these processes are usually associated with poor vascular function. However, maternal vascular function is enhanced in pregnancy. It is not understood how this is achieved in the face of the adverse metabolic and inflammatory environment. Research into cardiovascular disease demonstrates that plasma HDL (high-density lipoprotein), by merit of its functionality rather than its plasma concentration, exerts protective effects on the vascular endothelium. HDL has vasodilatory, antioxidant, anti-thrombotic and anti-inflammatory effects, and can protect against endothelial cell damage. In pregnancy, the plasma HDL concentration starts to rise at 10 weeks of gestation, peaking at 20 weeks. The initial rise in plasma HDL occurs around the time of the establishment of the feto-placental circulation, a time when the trophoblast plugs in the maternal spiral arteries are released, generating oxidative stress. Thus there is the intriguing possibility that new HDL of improved function is synthesized around the time of the establishment of the feto-placental circulation. In obese pregnancy and, to a greater extent, in pre-eclampsia, plasma HDL levels are significantly decreased and maternal vascular function is reduced. Wire myography studies have shown an association between the plasma content of apolipoprotein AI, the major protein constituent of HDL, and blood vessel relaxation. These observations lead us to hypothesize that HDL concentration, and function, increases in pregnancy in order to protect the maternal vascular endothelium and that in pre-eclampsia this fails to occur. PMID- 26888562 TI - Factors associated with photoprotection by body clothing coverage, particularly in non-summer months, among a New Zealand community sample. AB - Clothing coverage is important for reducing skin cancer risk, but may also influence vitamin D sufficiency, so associated plausible predictors require investigation. Volunteers (18 to 85 years), with approximately equal numbers by sex and four ethnicity groups, were recruited in cities from two latitude bands: Auckland (36.9 degrees S) and Dunedin (45.9 degrees S). Baseline questionnaire, anthropometric and spectrophotometer skin colour data were collected and weather data obtained. Percent body coverage was calculated from eight week diary records. Potential independent predictors (unadjusted p < 0.25) were included in adjusted models. Participants (n = 506: Auckland n = 334, Dunedin n = 172; mean age 48.4 years) were 62.7% female and had a median body clothing coverage of 81.6% (IQR 9.3%). Dunedin was cooler, less windy and had lower UVI levels than Auckland. From the fully adjusted model, increased coverage occurred in non summer months (despite adjusting for weather), among Dunedin residents and Asians (compared to Europeans), during the middle of the day, with a dose response effect observed for greater age. Reduced coverage was associated with Pacific ethnicity and greater time spent outdoors. Additionally, higher temperatures were associated with reduced coverage, whereas increased cloud cover and wind speed were associated with increased coverage. Although the only potentially modifiable factors associated with clothing coverage were the time period and time spent outdoors, knowledge of these and other associated factors is useful for the framing and targeting of health promotion messages to potentially influence clothing coverage, facilitate erythema avoidance and maintain vitamin D sufficiency. PMID- 26888560 TI - NOX2-dependent regulation of inflammation. AB - NADPH oxidase (NOX) isoforms together have multiple functions that are important for normal physiology and have been implicated in the pathogenesis of a broad range of diseases, including atherosclerosis, cancer and neurodegenerative diseases. The phagocyte NADPH oxidase (NOX2) is critical for antimicrobial host defence. Chronic granulomatous disease (CGD) is an inherited disorder of NOX2 characterized by severe life-threatening bacterial and fungal infections and by excessive inflammation, including Crohn's-like inflammatory bowel disease (IBD). NOX2 defends against microbes through the direct antimicrobial activity of reactive oxidants and through activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the breakdown of cell membranes and extracellular release of chromatin and neutrophil granular constituents that target extracellular pathogens. Although the immediate effects of oxidant generation and NETosis are predicted to be injurious, NOX2, in several contexts, limits inflammation and injury by modulation of key signalling pathways that affect neutrophil accumulation and clearance. NOX2 also plays a role in antigen presentation and regulation of adaptive immunity. Specific NOX2-activated pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor that induces antioxidative and cytoprotective responses, may be important therapeutic targets for CGD and, more broadly, diseases associated with excessive inflammation and injury. PMID- 26888563 TI - Population structure and minimum core genome typing of Legionella pneumophila. AB - Legionella pneumophila is an important human pathogen causing Legionnaires' disease. In this study, whole genome sequencing (WGS) was used to study the characteristics and population structure of L. pneumophila strains. We sequenced and compared 53 isolates of L. pneumophila covering different serogroups and sequence-based typing (SBT) types (STs). We found that 1,896 single-copy orthologous genes were shared by all isolates and were defined as the minimum core genome (MCG) of L. pneumophila. A total of 323,224 single-nucleotide polymorphisms (SNPs) were identified among the 53 strains. After excluding 314,059 SNPs which were likely to be results of recombination, the remaining 9,165 SNPs were referred to as MCG SNPs. Population Structure analysis based on MCG divided the 53 L. pneumophila into nine MCG groups. The within-group distances were much smaller than the between-group distances, indicating considerable divergence between MCG groups. MCG groups were also supplied by phylogenetic analysis and may be considered as robust taxonomic units within L. pneumophila. Among the nine MCG groups, eight showed high intracellular growth ability while one showed low intracellular growth ability. Furthermore, MCG typing also showed high resolution in subtyping ST1 strains. The results obtained in this study provided significant insights into the evolution, population structure and pathogenicity of L. pneumophila. PMID- 26888564 TI - A Novel Brainstem Hemorrhage Model by Autologous Blood Infusion in Rat: White Matter Injury, Magnetic Resonance Imaging, and Neurobehavioral Features. AB - BACKGROUND: Primary brainstem hemorrhage (BSH) has the highest mortality and morbidity as a subtype of intracerebral hemorrhage. A major limitation of BSH research is the lack of a corresponding animal model. The purpose of this study was to establish a novel rat model of BSH and to characterize the resulting brain injury, especially focusing on white matter injury. METHODS: BSH was produced by stereotactically injecting autologous whole blood into the pons. Time course of hematoma resolution was observed by 7-T magnetic resonance imaging. White matter injury was evaluated in detail by multiple parameters including diffuse tensor imaging (DTI), demyelination, axonal injury, oligodendrocyte degeneration, and oligodendrocyte precursor cell proliferation. Brain water content and neurobehavior were also evaluated. RESULTS: Blood infusion (30 uL) led to a stable, reproducible hematoma in the right basotegmental pons. The hematoma absorption started, became obvious, and was nearly completed at 7, 14, and 30 days, respectively. Hematoma caused obvious brain edema at 3 days. White mater injury was observed pathologically, which was in line with decreased fractional anisotropy (FA) in DTI in the pons. FA reduction was also noticed in the cerebral peduncle and medulla. Behavioral abnormality persisted for at least 14 days and neurofunction was recovered within 1 month. CONCLUSIONS: This novel model can produce a stable hematoma resulting in brain edema, white matter injury, and neurofunctional deficits, which could be useful for future investigation of pathophysiological mechanisms and new treatment evaluation after BSH. PMID- 26888565 TI - Cortical contributions to the flail leg syndrome: Pathophysiological insights. AB - Cortical hyperexcitability has been identified as an intrinsic feature of amyotrophic lateral sclerosis (ALS). Consequently, the aim of the present study was to determine whether cortical hyperexcitability formed the pathophysiological basis for the flail leg syndrome (FL), an atypical ALS variant. Cortical excitability studies were undertaken on 18 FL patients, using the threshold tracking transcranial magnetic stimulation (TMS) technique, and results were compared to healthy controls, upper and lower limb-onset ALS as well as bulbar onset and the flail arm variant ALS. Results showed that cortical hyperexcitability was a feature of FL and was heralded by a significant reduction of short-interval intracortical inhibition (FL 7.2 +/- 1.8%; controls 13.2 +/- 0.8%, p <0.01) and cortical silent period (CSP) duration (FL 181.7 +/- 10.8ms; controls 209.8 +/- 3.4ms; p <0.05) along with an increase in motor evoked potential amplitude (FL 29.2 +/- 5.1%; controls 18.9 +/- 1.2%, p <0.05). The degree of cortical hyperexcitability was comparable between FL and other ALS phenotypes, defined by site of disease onset. In addition, the CSP duration correlated with biomarkers of peripheral neurodegeneration in FL. In conclusion, cortical hyperexcitability is a feature of the flail leg syndrome, being comparable to other ALS phenotypes. Importantly, cortical hyperexcitability correlates with neurodegeneration, and as such may contribute to the underlying pathophysiology in FL. PMID- 26888567 TI - Using (FH)2 and (FH)3 to Bridge the sigma-Hole and the Lone Pair at P in Complexes with H2 XP, for X=CH3 , OH, H, CCH, F, Cl, NC, and CN. AB - Ab initio MP2/aug'-cc-pVTZ calculations are used to investigate the binary complexes H2 XP:HF, the ternary complexes H2 XP:(FH)2 , and the quaternary complexes H2 XP:(FH)3 , for X=CH3 , OH, H, CCH, F, Cl, NC, and CN. Hydrogen bonded (HB) binary complexes are formed between all H2 XP molecules and FH, but only H2 FP, H2 ClP, and H2 (NC)P form pnicogen-bonded (ZB) complexes with FH. Ternary complexes with (FH)2 are stabilized by F-H???P and F-H???F hydrogen bonds and F???P pnicogen bonds, except for H2 (CH3 )P:(FH)2 and H3 P:(FH)2 , which do not have pnicogen bonds. All quaternary complexes H2 XP:(FH)3 are stabilized by both F-H???P and F-H???F hydrogen bonds and P???F pnicogen bonds. Thus, (FH)2 with two exceptions, and (FH)3 can bridge the sigma-hole and the lone pair at P in these complexes. The binding energies of H2 XP:(FH)3 complexes are significantly greater than the binding energies of H2 XP:(FH)2 complexes, and nonadditivities are synergistic in both series. Charge transfer occurs across all intermolecular bonds from the lone-pair donor atom to an antibonding sigma* orbital of the acceptor molecule, and stabilizes these complexes. Charge-transfer energies across the pnicogen bond correlate with the intermolecular P-F distance, while charge-transfer energies across F-H???P and F-H???F hydrogen bonds correlate with the distance between the lone-pair donor atom and the hydrogen bonded H atom. In binary and quaternary complexes, charge transfer energies also correlate with the distance between the electron-donor atom and the hydrogen bonded F atom. EOM-CCSD spin-spin coupling constants (2h) J(F-P) across F-H???P hydrogen bonds, and (1p) J(P-F) across pnicogen bonds in binary, ternary, and quaternary complexes exhibit strong correlations with the corresponding intermolecular distances. Hydrogen bonds are better transmitters of F-P coupling data than pnicogen bonds, despite the longer F???P distances in F-H???P hydrogen bonds compared to P???F pnicogen bonds. There is a correlation between the two bond coupling constants (2h) J(F-F) in the quaternary complexes and the corresponding intermolecular distances, but not in the ternary complexes, a reflection of the distorted geometries of the bridging dimers in ternary complexes. PMID- 26888566 TI - Reduced brain activation in violent adolescents during response inhibition. AB - Deficits in inhibitory control have been linked to aggression and violent behaviour. This study aimed to observe whether violent adolescents show different brain activation patterns during response inhibition and to ascertain the roles these brain regions play. A self-report method and modified overt aggression scale (MOAS) were used to evaluate violent behaviour. Functional magnetic resonance imaging was performed in 22 violent adolescents and 17 matched healthy subjects aged 12 to 18 years. While scanning, a go/no-go task was performed. Between-group comparisons revealed that activation in the bilateral middle and superior temporal gyrus, hippocampus, and right orbitofrontal area (BA11) regions were significantly reduced in the violent group compared with the control group. Meanwhile, the violent group had more widespread activation in the prefrontal cortex than that observed in the control group. Activation of the prefrontal cortex in the violent group was widespread but lacking in focus, failing to produce intensive activation in some functionally related regions during response inhibition. PMID- 26888568 TI - Association of caregiver quality of care with neurocognitive outcomes in HIV affected children aged 2-5 years in Uganda. AB - Children affected by HIV are at increased risk of developmental and neuropsychological disturbances due to direct effects of HIV on the brain and direct effects associated with living in poverty. Caregivers can play an important role, through quality caregiving, in mitigating the negative effect of these stressors. This study used baseline data from an ongoing caregiver training intervention trial to evaluate the association between quality of caregiver-child interactions and neurocognitive outcomes in rural HIV-infected and HIV-exposed but uninfected children in Uganda. We also assessed the extent to which caregiver distress moderated this relationship. Data on 329 caregiver-child dyads were collected between March 2012 and July 2014, when the children were between 2 and 5 years of age. Child outcomes include the Mullen Scales of Early Learning to assess general cognitive ability and the Color Object Association Test to assess immediate memory and total recall. Caregiving quality was assessed using the Home Observation for the Measurement of the Environment (HOME) total and subscale scores. Caregiver distress was assessed using the Hopkins Symptom Checklist. General linear regression models assessed the association between the HOME total and subscale scores and child outcomes, with interaction terms used to test moderation by caregiver distress. Total HOME scores were positively and significantly associated with Mullen scores of cognitive ability; HOME acceptance subscale scores were positively and significantly associated with immediate recall scores. No other associations were statistically significant. As hypothesized, there is a strong association between the HOME and Mullen scores of cognitive ability in our study population, such that children who were assessed as living in environments with more stimulation also presented with a higher level of general neurocognitive development. Our results support the view of program guidance for HIV-affected children that suggest family-oriented care with emphasis on parent-child relationships for optimal child development. PMID- 26888569 TI - PbsP, a cell wall-anchored protein that binds plasminogen to promote hematogenous dissemination of group B Streptococcus. AB - Streptococcus agalactiae (Group B Streptococcus or GBS) is a leading cause of invasive infections in neonates whose virulence is dependent on its ability to interact with cells and host components. We here characterized a surface protein with a critical function in GBS pathophysiology. This adhesin, designated PbsP, possesses two Streptococcal Surface Repeat domains, a methionine and lysine-rich region, and a LPXTG cell wall-anchoring motif. PbsP mediates plasminogen (Plg) binding both in vitro and in vivo and we showed that cell surface-bound Plg can be activated into plasmin by tissue plasminogen activator to increase the bacterial extracellular proteolytic activity. Absence of PbsP results in a decreased bacterial transmigration across brain endothelial cells and impaired virulence in a murine model of infection. PbsP is conserved among the main GBS lineages and is a major plasminogen adhesin in non-CC17 GBS strains. Importantly, immunization of mice with recombinant PbsP confers protective immunity. Our results indicate that GBS have evolved different strategies to recruit Plg which indicates that the ability to acquire cell surface proteolytic activity is essential for the invasiveness of this bacterium. PMID- 26888570 TI - Comparison of objective refraction in darkness to cycloplegic refraction: a pilot study. AB - BACKGROUND: The aim was to assess non-cycloplegic objective refraction in darkness using an open-field auto-refractor, and furthermore to compare it with distance cycloplegic subjective refraction and distance cycloplegic retinoscopy in the light, in children and young adults. METHODS: Twenty-three, visually normal, young-adults (46 eyes) ages 23 to 31 years, and five children (10 eyes) ages five to 12 years, participated in the study. The spherical component of their refraction ranged from -2.25 D to +3.75 D with a mean of +1.80 D, and a mean cylinder of -0.70 D. Three techniques were used to assess refractive error. An objective measure of the non-cycloplegic refractive state was obtained using an open-field autorefractor (WAM-5500) after five minutes in the dark to allow for dissipation of accommodative transients and relaxation of accommodation. In addition, both distance retinoscopy and subjective distance refraction were performed following cycloplegia (Cyclopentolate, 1%) using conventional clinical procedures. All measurements were obtained on the same day within a single session. The spherical component of the refraction was compared among the three techniques in both the children and adults. RESULTS: There was no significant difference in spherical refraction among the three techniques: non-cycloplegic objective refraction in the dark, distance cycloplegic retinoscopy and distance cycloplegic subjective refraction, in either the adults [F(2, 137) = 0.79, p = 0.45] or the children [F(2, 27) = 0.47, p = 0.62]. Mean difference in the spherical component between refraction in the dark and the cycloplegic distance retinoscopy was -0.34 D (r = 0.89) in the adults and +0.14 D (r = 0.96) in the children. The mean difference in spherical component between refraction in the dark and the cycloplegic distance subjective refraction was -0.25 D (r = 0.92) in the adults and -0.05 D (r = 0.95) in the children. CONCLUSION: Comparison of the spherical refractive component between the three techniques was not significantly different and furthermore, they were highly correlated in both the children and adults in this pilot study. Non-cycloplegic refraction in the dark may provide a reliable adjunct or alternative to conventional cycloplegic refraction in both children and young adults. PMID- 26888571 TI - Differential migration and the link between winter latitude, timing of migration, and breeding in a songbird. AB - Patterns of connectivity between breeding and wintering grounds can have important implications for individual fitness and population dynamics. Using light-level geolocators and stable hydrogen isotopes (delta(2)H) in feathers, we evaluated differential migration of Savannah sparrows (Passerculus sandwichensis) breeding on Kent Island in the Bay of Fundy, New Brunswick, Canada in relation to sex, age, and body size. Based on geolocators recovered from 38 individuals between 2012 and 2014, the winter distribution was centered in North Carolina (median latitude 34 degrees , range 26 degrees -41 degrees ), with males overwintering, on average, approximately 275 km further north than females. Based on analyses of tail feather samples collected from 106 individuals from the same population between 2008 and 2012, males and adults had more negative delta(2)H values than females and juveniles, respectively, providing additional evidence that males wintered north of females and that adults wintered north of juveniles. Winter latitude and delta(2)H values within each sex were not found to be related to body size. From geolocator data, males returned to the breeding grounds, on average, 14 days earlier than females. For males, there was some evidence that arrival date on the breeding grounds was negatively correlated with winter latitude and that individuals which arrived earlier tended to breed earlier. Thus, benefits for males of early arrival on the breeding grounds may have contributed to their wintering farther north than females. Social dominance may also have contributed to age and sex differences in winter latitude, whereby dominant males and adults forced subordinate females and juveniles further south. PMID- 26888573 TI - Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders. AB - Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care. PMID- 26888572 TI - Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban. AB - OBJECTIVE: To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD). METHODS: Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis. RESULTS: Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31). CONCLUSIONS: We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD. TRIAL REGISTRATION NUMBER: NCT00403767; Post-results. PMID- 26888574 TI - Predominance of synovial sensory nerve fibers in arthrofibrosis following total knee arthroplasty compared to osteoarthritis of the knee. AB - BACKGROUND: So far, there exists no golden standard for the treatment of arthrofibrosis (AF) following total knee arthroplasty (TKA). Although pain is a hallmark of AF, nociceptive nerve fibers have never been investigated in affected joint tissue. METHODS: A total of 24 patients with osteoarthritis (OA) of the knee (n = 12) and post-TKA AF of the knee (n = 12) were included. Along evaluation of typical clinical signs and symptoms by using the Knee Society Clinical Rating System (KSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC index), the innervation of joint tissue was studied by semiquantitative immunofluorescence of nerve fibers. RESULTS: Patients with AF compared to OA had a lower KSS and lower KOOS. In all compartments (anterior, medial, and lateral recesses), the density of synovial sympathetic nerve fibers was significantly higher in OA compared to AF, which was also true for the density of sensory nerve fibers in the medial and lateral recesses. In synovial tissue of the anterior recess of patients with AF compared to OA, the density of nociceptive sensory nerve fibers was significantly higher relative to sympathetic nerve fibers. This was similarly observed in the neighboring infrapatellar fat pad of the knee. CONCLUSIONS: Similar as in many painful musculoskeletal diseases, this study indicates that patients with arthrofibrosis of the knee after TKA demonstrate a preponderance of profibrotic sensory nerve fibers over antifibrotic sympathetic nerve fibers. This could serve as a starting point for AF therapy with specific antifibrotic pain medication or regional anesthetic techniques. PMID- 26888577 TI - Breastfeeding in mothers with systemic lupus erythematosus. AB - INTRODUCTION: Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. METHODS: Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. RESULTS: A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n = 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. CONCLUSION: Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding. PMID- 26888578 TI - Three-dimensional porous hollow fibre copper electrodes for efficient and high rate electrochemical carbon dioxide reduction. AB - Aqueous-phase electrochemical reduction of carbon dioxide requires an active, earth-abundant electrocatalyst, as well as highly efficient mass transport. Here we report the design of a porous hollow fibre copper electrode with a compact three-dimensional geometry, which provides a large area, three-phase boundary for gas-liquid reactions. The performance of the copper electrode is significantly enhanced; at overpotentials between 200 and 400 mV, faradaic efficiencies for carbon dioxide reduction up to 85% are obtained. Moreover, the carbon monoxide formation rate is at least one order of magnitude larger when compared with state of-the-art nanocrystalline copper electrodes. Copper hollow fibre electrodes can be prepared via a facile method that is compatible with existing large-scale production processes. The results of this study may inspire the development of new types of microtubular electrodes for electrochemical processes in which at least one gas-phase reactant is involved, such as in fuel cell technology. PMID- 26888576 TI - Neuroimaging evidence of deficient axon myelination in Wolfram syndrome. AB - Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain. PMID- 26888579 TI - How to be a dioecious fig: Chemical mimicry between sexes matters only when both sexes flower synchronously. AB - In nursery pollination mutualisms, which are usually obligate interactions, olfactory attraction of pollinators by floral volatile organic compounds (VOCs) is the main step in guaranteeing partner encounter. However, mechanisms ensuring the evolutionary stability of dioecious fig-pollinator mutualisms, in which female fig trees engage in pollination by deceit resulting in zero reproductive success of pollinators that visit them, are poorly understood. In dioecious figs, individuals of each sex should be selected to produce odours that their pollinating wasps cannot distinguish, especially since pollinators have usually only one choice of a nursery during their lifetime. To test the hypothesis of intersexual chemical mimicry, VOCs emitted by pollen-receptive figs of seven dioecious species were compared using headspace collection and gas chromatography mass spectrometry analysis. First, fig-flower scents varied significantly among species, allowing host-species recognition. Second, in species in which male and female figs are synchronous, intersexual VOC variation was not significant. However, in species where figs of both sexes flower asynchronously, intersexual variation of VOCs was detectable. Finally, with one exception, there was no sexual dimorphism in scent quantity. We show that there are two ways to use scent to be a dioecious fig based on differences in flowering synchrony between the sexes. PMID- 26888580 TI - Adenosine diphosphate platelet dysfunction on thromboelastogram is independently associated with increased morality in traumatic brain injury. AB - PURPOSE: The purpose of this study is to determine if adenosine diphosphate (ADP) platelet dysfunction on thromboelastogram (TEG) is associated with increased in hospital mortality in patients with head trauma. The hypothesis is that ADP dysfunction is associated with increased mortality. METHODS: This retrospective review evaluated trauma patients admitted to a level 1 trauma center from February 2011 to October 2013 who received a TEG. Patients were included if the TEG was drawn within the first 24 h of admission and the head abbreviated injury score was greater than or equal to three. Patients were categorized as severe ADP dysfunction if the degree of ADP inhibition on TEG exceeded 60 %. RESULTS: A total of 90 patients were included (no ADP dysfunction n = 37; ADP dysfunction n = 53). Initial Glasgow Coma Scale [GCS (12 +/- 4 vs. 11 +/- 5; p = 0.26)] and use of pre-injury antiplatelet agents (30 vs. 28 %; p = 0.88) were similar. Patients with ADP dysfunction on TEG had a higher in-hospital mortality rate (8 vs. 32 %; p < 0.01). ADP dysfunction was independently associated with in-hospital mortality upon fixed logistic regression (OR 6.2; 95 % CI 1.2-33) while controlling for age, gender, hypotension, pre-injury antiplatelet agents, GCS and Injury Severity Score. CONCLUSION: ADP dysfunction on TEG is associated with increased mortality in patients with traumatic brain injury. PMID- 26888581 TI - Histological and immunohistochemical characterization of feline renal cell carcinoma: a case series. AB - Four feline renal cell carcinomas (RCCs) were examined using histopathological and immunohistochemical procedures. Specimens were classified by predominant histological pattern according to WHO criteria. A panel of antibodies including beta-catenin, C-KIT, VEGF and VEGF-R2 and double immunostaining for vimentin/cytokeratin and for E-cadherin/CD10 was selected to characterize the tumors. Neoplasms were classified as tubular (3/4) and papillary (1/4). Neoplastic epithelial cells were cytokeratin, vimentin, E-cadherin, VEGF-R2 positive and C-KIT negative; 3 cases were beta-catenin positive, whereas only 2 tumors were CD10 and VEGF positive. No correlation with histotype was evident. Our results confirm the low frequency of RCCs in cats and suggest a histological pattern similar to canine RCCs. In contrast, a peculiar immunohistochemical profile different from both canine and human RCCs is identified. PMID- 26888582 TI - Roles of DNA mutation in the coding region and DNA methylation in the 5' flanking region of BRCA1 in canine mammary tumors. AB - The Breast cancer 1, early onset gene (BRCA1) is known to be significantly associated with human familial breast cancer and is identified to play an important role in canine mammary tumors. Here, genetic variations in the coding region and DNA methylation in the 5' flanking region of BRCA1 in canine mammary tumor samples, 15 each of benign and malignant against 10 normal canine mammary tissue samples, were analyzed using the direct sequencing method. The results indicated two point mutations each in the coding region of canine BRCA1 in one benign mammary tumor sample (4702G >T and 4765G >T) and in one malignant canine mammary tumor sample (3619A >G and 4006G >A). No mutations were detected in the normal canine mammary tissue samples. The 4702G >T mutation was found to terminate further translation. The physical effect of the 4765G >T mutation was found to be the repalacement of the glutamate residue with glutamine. The physical effect of the 3619A >G mutation was found to be the replacement of the threonine residue with alanine, and that of mutation 4006G >A was the replacement of the valine residue with isoleucine in the BRCA1 protein. Bisulfite sequencing detected methylated CpG sites in one canine malignant mammary tumor sample. In conclusion, the present study elucidated the mutational status of the BRCA1 coding region and methylation status of the 5' flanking region of BRCA1 in canine mammary tumors. PMID- 26888583 TI - Detection of circulating tumor cells using GeneScan analysis for antigen receptor gene rearrangements in canine lymphoma patients. AB - The presence of circulating tumor cells (CTCs) serves as a prognostic marker and indicator of disease relapse, as well as a means of evaluating treatment efficacy in human and canine lymphoma patients. As an extension of our previous study for the construction of clinically useful GeneScan system, we utilized the GeneScan system for detecting CTCs in canine lymphoma patients. Samples from the primary lesion and peripheral blood mononuclear cells (PBMCs) were obtained from 32 dogs with lymphoma at initial diagnosis. All samples were subjected to polymerase chain reaction (PCR) for antigen receptor gene rearrangements (PARR) followed by GeneScan analysis. Common clonal rearrangements with identical amplified fragments were detected in both the primary lesion and PBMCs in 19 of the 32 dogs (59.4%). However, the detection rate of CTCs varied among the anatomical classification of lymphoma studied. GeneScan analysis following PARR would facilitate studies on determining the clinical significance of CTCs in canine lymphoma patients. PMID- 26888584 TI - Characterization of equine hyalocytes: their immunohistochemical properties, morphologies and distribution. AB - In horse, the characterizations of hyalocytes under the steady state are still unclear. Therefore, we investigated characterizations of hyalocytes in normal equine eyes by their immunohistochemical phenotype, histomorphology and distribution. Thirty-one eyes from 18 horses, divided into 4 groups (G) by age, were used: early (G1) and late gestation (G2) fetuses, 1- to 3-year-old (G3) and 8- to 24-year-old (G4) horses. Equine hyalocytes were histologically classified into 4 types, and they immunohistochemically expressed MHC II and CD163. Hyalocytes were detected on and/or around ciliary processes and pars plana in G2, G3 and G4, but were not located on retina and optic papilla. A significant increase in distribution was found between G2 and both G3 and G4, and the largest distribution was found at ciliary processes in these groups. Equine hyalocytes were characterized as residential ocular macrophage and MHC II antigen-bearing cell, accompanied by a pleomorphic appearance and located in the contiguous ciliary body. Our data provided characterizations of hyalocytes in normal equine eyes and may well contribute to improving the understanding of pathogenesis of equine ocular disease. PMID- 26888585 TI - Persistence of chicken anemia virus antigen and inclusions in spontaneous cases of Marek's disease visceral lymphomas in broiler chickens at slaughterhouses. AB - The chicken anemia virus (CAV) and Marek's disease virus (MDV) infect chickens worldwide; a single or dual infection by these viruses has a great impact on poultry production. In the present study, we examined the existence of CAV antigen and its inclusions in Marek's disease (MD) lymphomas in chickens in the slaughterhouses of Iwate prefecture, Japan. Forty-nine spleens and 13 livers with different degrees of nodular lesions were histopathologically examined at our laboratory. Grossly, the tested organs showed various sizes and anatomical architectures. Based on the cellular morphology and the infiltrative nature of the neoplastic lymphocytes, MD was confirmed in 76% (37/49) of the spleens and 92% (12/13) of the livers. The lesions of MD, according to the pattern of lymphocytic accumulation in the affected organs, were divided into multifocal, coalesced and diffuse. CAV intranuclear inclusion bodies were detected within the small and the large bizarre lymphocytes of the MD lymphomas in 2 livers and 9 spleens, and the immunostaining test for CAV confirmed the persistence of CAV antigens and inclusions in the neoplastic cells. This study demonstrated the persistence of CAV infection within the neoplastic cells of naturally occurring MD lymphomas in chickens. PMID- 26888586 TI - CBT-I Coach: A Description and Clinician Perceptions of a Mobile App for Cognitive Behavioral Therapy for Insomnia. AB - STUDY OBJECTIVES: This paper describes CBT-I Coach, a patient-facing smartphone app designed to enhance cognitive behavioral therapy for insomnia (CBT-I). It presents findings of two surveys of U.S. Department of Veterans Affairs (VA) CBT I trained clinicians regarding their perceptions of CBT-I Coach before it was released (n = 138) and use of it two years after it was released (n = 176). METHODS: VA-trained CBT-I clinicians completed web-based surveys before and two years after CBT-I Coach was publicly released. RESULTS: Prior to CBT-I Coach release, clinicians reported that it was moderately to very likely that the app could improve care and a majority (87.0%) intended to use it if it were available. Intention to use the app was predicted by smartphone ownership (beta = 0.116, p < 0.05) and perceptions of relative advantage to existing CBT-I practices (beta = 0.286, p < 0.01), compatibility with their own needs and values (beta = 0.307, p < 0.01), and expectations about the complexity of the app (beta = 0.245, p < 0.05). Two years after CBT-I Coach became available, 59.9% of participants reported using it with patients and had favorable impressions of its impact on homework adherence and outcomes. CONCLUSIONS: Findings suggest that before release, CBT-I Coach was perceived to have potential to enhance CBT-I and address common adherence issues and clinicians would use it. These results are reinforced by findings two years after it was released suggesting robust uptake and favorable perceptions of its value. PMID- 26888587 TI - Effects of Continuous Positive Airway Pressure on Cognitive and Functional Outcome of Stroke Patients with Obstructive Sleep Apnea: A Randomized Controlled Trial. AB - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) in stroke patients is associated with worse functional and cognitive status during inpatient rehabilitation. We hypothesized that a four-week period of continuous positive airway pressure (CPAP) treatment would improve cognitive and functional outcomes. METHODS: We performed a randomized controlled trial in stroke patients admitted to a neurorehabilitation unit. Patients were assigned to rehabilitation treatment as usual (control group) or to CPAP treatment (CPAP group). Primary outcomes were cognitive status measured by neuropsychological examination, and functional status measured by two neurological scales and a measure of activities of daily living (ADL). Secondary measures included sleepiness, sleep quality, fatigue, and mood. Tests were performed at baseline and after the four-week intervention period. RESULTS: We randomly assigned 20 patients to the CPAP group and 16 patients to the control group. The average CPAP compliance was 2.5 hours per night. Patients in the CPAP group showed significantly greater improvement in the cognitive domains of attention and executive functioning than the control group. CPAP compliance was associated with greater improvement in cognitive functioning. CPAP did not result in measurable improvement on measures of neurological status or ADL, or on any of the secondary measures. CONCLUSIONS: CPAP treatment improves cognitive functioning of stroke patients with OSA. COMMENTARY: A commentary on this article appears in this issue on page 467. PMID- 26888588 TI - High Adherence to CPAP Treatment Does Not Prevent the Continuation of Weight Gain among Severely Obese OSAS Patients. AB - STUDY OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) patients benefit from continuous positive airway pressure (CPAP) treatment in a dose-response manner. We determined adherence and weight control, as well as their predictors, among long-term CPAP users. METHODS: Cohort of 1,023 OSAS patients had used CPAP on average of 6.6 +/- 1.2 years. BMI was determined at baseline and at follow-up visits. There were 7.4 +/- 1.7 BMI and 6.5 +/- 1.8 CPAP usage measurements per patient on average. Using the Bayesian hierarchical model, we determined the patients' individual trends of BMI and adherence development. Patients with significantly increasing or decreasing trends were identified at the posterior probability level of > 90%. RESULTS: The mean age in the cohort was 55.6 +/- 9.8 years, BMI 33.5 +/- 6.4 kg/m(2), apnea-hypopnea index 33.7 +/- 23.1, and CPAP usage 6.0 +/- 1.8 h/day. The majority of patients had no significant change in BMI (mean annual weight gain 0.04 +/- 0.29 kg/m(2)) or CPAP adherence (mean annual increase 11.4 +/- 7.0 min/day). However, at the individual level, 10% of the patients showed significant annual weight gain (0.63 +/- 0.35 kg/m(2)) during the 5-year follow-up period. At baseline these patients were already more severely obese (mean BMI 40.0 +/- 5.9 kg/m(2)) despite being younger (mean 50.9 +/- 9.5 years) than the rest of the cohort. CONCLUSIONS: In the majority of CPAP treated OSAS patients, weight did not significantly change but gained slightly slower than in age-matched population in general. However, in 10% of patients, high adherence to CPAP treatment did not prevent the continuation of weight gain. These patients present a high-risk group for OSAS-related multimorbidity later in life. PMID- 26888589 TI - Body Position May Influence Oronasal CPAP Effectiveness to Treat OSA. AB - CPAP applied by a nasal mask is the gold standard treatment of obstructive sleep apnea. Oronasal masks are an alternative interface that can be used, especially in subjects with predominant oral breathing. However, oronasal masks have higher costs, are associated with larger leaks and higher residual apnea-hypopnea index, and in some cases may be ineffective. PMID- 26888590 TI - Healthcare Use in Individuals with Obesity and Chronic Hypoxemia Treated for Sleep Disordered Breathing. AB - STUDY OBJECTIVES: To determine if treatment of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) among patients with chronic hypoxemia is associated with reduced healthcare utilization. METHODS: We performed a retrospective cohort study of 129 obese, hypoxemic patients who underwent polysomnography and were prescribed positive airway pressure (PAP) therapy. During a 2-year follow-up period we examined the associations between adherence to PAP therapy and rates of hospitalization, emergency room (ER) visits, and outpatient visits. RESULTS: Severe OSA and OHS were common, as were hypertension, cardiovascular, and pulmonary disease. Forty-nine percent of patients were adherent with PAP therapy. Compared to patients who were not adherent to PAP therapy, adherent patients had significantly lower rates of all-cause hospitalization (incident rate ratio [IRR]:0.55, 95% CI 0.33, 0.93) after adjustment for age, sex and hospitalisation rates prior to treatment. Adjustment for additional comorbidities attenuated this association (IRR: 0.61, 95% CI 0.35, 1.06). Adherence with PAP therapy was associated with lower odds of frequent hospitalization (odds ratio 0.23, 95% CI 0.07, 0.73). There were no significant differences in the rates of ER or outpatient visits between adherent and non adherent patients. CONCLUSIONS: Adherence with PAP treatment in patients with chronic hypoxemia and chronic medical disorders is associated with reduced rates of hospitalization, which has significant benefit both for patients and the healthcare system. PMID- 26888591 TI - Influence of a Post-Test Factor on the Results of the Multiple Sleep Latency Test. AB - STUDY OBJECTIVES: The multiple sleep latency test (MSLT) is the standard method for the objective measurement of excessive daytime sleepiness. It is well established that preceding factors may influence the MSLT result. Aim of this study was to evaluate the potential influence of a post-test factor on the MSLT outcome. METHODS: For this retrospective study we reviewed polysomnography (PSG) reports conducted between 2012 and 2013. PSG reports including MSLT with at least four runs were included. Patients were stratified into (1) those discharged immediately after the MSLT or (2) those discharged on the following day. For further analysis, we categorized the patients into three subgroups according to mean MSLT sleep latency: < 5, 5-9.9, and 10-19.9 minutes, corresponding to a pathological, borderline, and normal MSLT result. RESULTS: A total of 2,749 PSG records were reviewed; 262 included MSLT and 241 met inclusion criteria for the study. Of those, 152 patients were discharged immediately after the last MSLT run, 89 on the following day. MSLT mean sleep latency, and sleep latency of the last run only, did not differ between both groups (p = 0.070 and p = 0.065). In the subgroup of patients with pathological MSLT, there was a trend towards prolonged sleep latency in the last run in patients discharged immediately after the test (p = 0.055). CONCLUSIONS: Our findings suggest that the MSLT post-test factor of discharge timing has no major impact on the MSLT outcome. PMID- 26888593 TI - Error in Calculation of Predictive Values in Paper on Screening for Sleep Bruxism. PMID- 26888594 TI - Adaptive Servo-Ventilation and Central Apnea Associated with Systolic Heart Failure. PMID- 26888592 TI - Subjective and Objective Measures of Hypersomnolence Demonstrate Divergent Associations with Depression among Participants in the Wisconsin Sleep Cohort Study. AB - STUDY OBJECTIVES: To examine associations of depression with habitual sleep duration, daytime sleepiness, and objective sleep propensity in a nonclinical population. METHODS: Data from adults participating in the Wisconsin Sleep Cohort Study were utilized in analyses. There were 1,287 adults (3,324 observations) who were used in the analysis of subjective hypersomnolence measures; 1,155 adults (2,981 observations) were used in the analysis of objective sleep propensity assessed by the multiple sleep latency test (MSLT). Repeated-measures logistic regression estimated associations between presence of depression (defined as modified Zung Self-Rating Depression Scale >= 50 or use of antidepressant medications) and three primary hypersomnolence measures: subjective excessive daytime sleepiness (Epworth Sleepiness Scale [ESS] >= 11), self-reported sleep duration >= 9 h/d, and objective sleep propensity (MSLT mean sleep latency < 8 min). RESULTS: After adjusting for age, sex, body mass index, chronic medical conditions, sedative hypnotic medication use, caffeine, tobacco, and alcohol use, sleep disordered breathing, as well as insomnia and sleep duration when appropriate, estimated odd ratios (95% confidence interval) for depression were: 1.56 (1.31,1.86) for ESS >= 11; 2.01 (1.49, 2.72) for habitual sleep time >= 9 h; and 0.76 (0.63-0.92) for MSLT mean sleep latency < 8 min. CONCLUSIONS: Our results demonstrate divergent associations between subjective and objective symptoms of hypersomnolence and depression, with subjective sleepiness and excessive sleep duration associated with increased odds of depression, but objective sleep propensity as measured by the MSLT associated with decreased odds of depression. Further research is indicated to explain this paradox and the impact of different hypersomnolence measures on the course of mood disorders. COMMENTARY: A commentary on this article appears in this issue on page 467. PMID- 26888595 TI - How Did It Get Late So Soon? PMID- 26888596 TI - CHO cells knocked out for TSC2 display an improved productivity of antibodies under fed batch conditions. AB - The kinase mTOR operates in two cellular complexes, mTORC1 and mTORC2. mTORC1 adjusts metabolic activity according to external growth conditions and nutrients availability. When conditions are prosperous, mTOR facilitates protein and lipid biosyntheses and inhibits autophagy, while under metabolic constraints, however, its attenuation induces a catabolic program, energy preservation and autophagy. CHO is a key cell line for manufacturing of biologics owing to its remarkable ability to grow to high densities and maintain protein production and secretion for extended times. While high mTOR activity has been associated with high productivity in CHO cells, its inhibition by rapamycin has also been documented to augment productivity via promotion of viability. Here using CRISPR/Cas9 editing we engineered CHO cells to enforce high mTORC1 activity by knocking-out TSC2, a major mTOR inhibitory protein, or PTEN, a phosphatase that attenuates the PI3K/AKT/mTOR pathway. Only TSC2-deleted cells exhibited a constitutive activation of mTORC1 under fed batch conditions. Cells grew larger in size, synthesized more proteins and displayed an over twofold elevation in their specific productivity. While peak viable cell density was compromised, overall titers increased to an extent dependent upon the parental clone. Our data underscore manipulation of TSC as a strategy to improve performance of CHO cell in bioreactors. Biotechnol. Bioeng. 2016;113: 1942-1952. (c) 2016 Wiley Periodicals, Inc. PMID- 26888598 TI - Influence of epidermal growth factor (EGF) and hydrocortisone on the co-culture of mature adipocytes and endothelial cells for vascularized adipose tissue engineering. AB - The composition of vascularized adipose tissue is still an ongoing challenge as no culture medium is available to supply adipocytes and endothelial cells appropriately. Endothelial cell medium is typically supplemented with epidermal growth factor (EGF) as well as hydrocortisone (HC). The effect of EGF on adipocytes is discussed controversially. Some studies say it inhibits adipocyte differentiation while others reported of improved adipocyte lipogenesis. HC is known to have lipolytic activities, which might result in mature adipocyte dedifferentiation. In this study, we evaluated the influence of EGF and HC on the co-culture of endothelial cells and mature adipocytes regarding their cell morphology and functionality. We showed in mono-culture that high levels of HC promoted dedifferentiation and proliferation of mature adipocytes, whereas EGF seemed to have no negative influence. Endothelial cells kept their typical cobblestone morphology and showed a proliferation rate comparable to the control independent of EGF and HC concentration. In co-culture, HC promoted dedifferentiation of mature adipocytes, which was shown by a higher glycerol release. EGF had no negative impact on adipocyte morphology. No negative impact on endothelial cell morphology and functionality could be seen with reduced EGF and HC supplementation in co-culture with mature adipocytes. Taken together, our results demonstrate that reduced levels of HC are needed for co-culturing mature adipocytes and endothelial cells. In co-culture, EGF had no influence on mature adipocytes. Therefore, for the composition of vascularized adipose tissue constructs, the media with low levels of HC and high or low levels of EGF can be used. PMID- 26888599 TI - Comparison of ultraviolet light-emitting diodes and low-pressure mercury-arc lamps for disinfection of water. AB - Ultraviolet (UV) light-emitting diodes (LEDs) emitting at 260 nm were evaluated to determine the inactivation kinetics of bacteria, viruses, and spores compared to low-pressure (LP) UV irradiation. Test microbes were Escherichia coli B, a non enveloped virus (MS-2), and a bacterial spore (Bacillus atrophaeus). For LP UV, 4 log10 reduction doses were: E. coli B, 6.5 mJ/cm(2); MS-2, 59.3 mJ/cm(2); and B. atrophaeus, 30.0 mJ/cm(2). For UV LEDs, the 4-log10 reduction doses were E. coli B, 6.2 mJ/cm(2); MS-2, 58 mJ/cm(2); and B. atrophaeus, 18.7 mJ/cm(2). Microbial inactivation kinetics of the two UV technologies were not significantly different for E. coli B and MS-2, but were different for B. atrophaeus spores. UV LEDs at 260 nm are at least as effective for inactivating microbes in water as conventional LP UV sources and should undergo further development in treatment systems to disinfect drinking water. PMID- 26888600 TI - Graphene-philic surfactants for nanocomposites in latex technology. AB - Graphene is the newest member of the carbon family, and has revolutionized materials science especially in the field of polymer nanocomposites. However, agglomeration and uniform dispersion remains an Achilles' heel (even an elephant in the room), hampering the optimization of this material for practical applications. Chemical functionalization of graphene can overcome these hurdles but is often rather disruptive to the extended pi-conjugation, altering the desired physical and electronic properties. Employing surfactants as stabilizing agents in latex technology circumvents the need for chemical modification allowing for the formation of nanocomposites with retained graphene properties. This article reviews the recent progress in the use of surfactants and polymers to prepare graphene/polymer nanocomposites via latex technology. Of special interest here are surfactant structure-performance relationships, as well as background on the roles surfactant-graphene interactions for promoting stabilization. PMID- 26888601 TI - Heterogeneous and Homogeneous Routes in Water Oxidation Catalysis Starting from Cu(II) Complexes with Tetraaza Macrocyclic Ligands. AB - Since the first report in 2012, molecular copper complexes have been proposed as efficient electrocatalysts for water oxidation reactions, carried out in alkaline/neutral aqueous media. However, in some cases the copper species have been recognized as precursors of an active copper oxide layer, electrodeposited onto the working electrode. Therefore, the question whether copper catalysis is molecular or not is particularly relevant in the field of water oxidation. In this study, we investigate the electrochemical activity of copper(II) complexes with two tetraaza macrocyclic ligands, distinguishing heterogeneous or homogeneous processes depending on the reaction media. In an alkaline aqueous solution, and upon application of an anodic bias to working electrodes, an active copper oxide layer is observed to electrodeposit at the electrode surface. Conversely, water oxidation in neutral aqueous buffers is not associated to formation of the copper oxide layer, and could be exploited to evaluate and optimize a molecular, homogeneous catalysis. PMID- 26888597 TI - Scandinavian guidelines for initial management of minor and moderate head trauma in children. AB - BACKGROUND: The management of minor and moderate head trauma in children differs widely between countries. Presently, there are no existing guidelines for management of these children in Scandinavia. The purpose of this study was to produce new evidence-based guidelines for the initial management of head trauma in the paediatric population in Scandinavia. The primary aim was to detect all children in need of neurosurgical intervention. Detection of any traumatic intracranial injury on CT scan was an important secondary aim. METHODS: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used. Systematic evidence-based review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and based upon relevant clinical questions with respect to patient-important outcomes. Quality ratings of the included studies were performed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and Centre of Evidence Based Medicine (CEBM)-2 tools. Based upon the results, GRADE recommendations, a guideline, discharge instructions and in hospital observation instructions were drafted. For elements with low evidence, a modified Delphi process was used for consensus, which included relevant clinical stakeholders. RESULTS: The guidelines include criteria for selecting children for CT scans, in-hospital observation or early discharge, and suggestions for monitoring routines and discharge advice for children and guardians. The guidelines separate mild head trauma patients into high-, medium- and low-risk categories, favouring observation for mild, low-risk patients as an attempt to reduce CT scans in children. CONCLUSIONS: We present new evidence and consensus based Scandinavian Neurotrauma Committee guidelines for initial management of minor and moderate head trauma in children. These guidelines should be validated before extensive clinical use and updated within four years due to rapid development of new diagnostic tools within paediatric neurotrauma. PMID- 26888603 TI - Decrease in serum potassium levels post saline suppression test in primary aldosteronism: an under-recognised phenomenon? PMID- 26888605 TI - Estimation of emission factor for odorants released from swine excretion slurries. AB - In this study, the odorant emission rates from excretory wastes collected in sealed containers from a large swine facility were determined offsite in a laboratory using both raw slurry from ([1] windowless pigpen (WP) and [2] open pigpen (OP)) and treated waste samples ([3] composting facility (CF) and [4] slurry treatment facility (SF)). The emission rates of up to 41 volatile odorants were measured for 100g waste samples (of all four types) in a 0.75L impinger with an air change rate of 8h(-1). The initial emission rates (mgkg(-1).h(-1)) for the most dominant species from each waste type can be summarized as: (1) WP: NH3 (16.3) and H2S (0.54); (2) OP: H2S (1.78), NH3 (1.69), and p-cresol (0.36); (3) CF: NH3 (7.04), CH3SH (0.30), and DMS (0.12); and (4) SF: NH3 (11.7), H2S (11.7), and p-cresol (0.25). Accordingly, the emission factors for the key odorant (mE, kg.pig(-1))) for fattening pigs in the WP and OP facilities of S. Korea were extrapolated as 3.46 (NH3) and 0.38 (H2S), respectively. The emission factors were estimated assuming exponentially decaying emission rates and slurry production rates obtained from the literature. PMID- 26888606 TI - Corrigendum to "Ambient volatile organic compounds and their effect on ozone production in Wuhan, central China" [Sci. Total Environ. 541 (2016) 200-209]. PMID- 26888602 TI - Alcoholic hepatitis accelerates early hepatobiliary cancer by increasing stemness and miR-122-mediated HIF-1alpha activation. AB - Alcohol-related hepatocellular carcinoma (HCC) develops with advanced alcoholic liver disease and liver fibrosis. Using adult mice, we evaluate the effect of alcoholic steatohepatitis on early hepatobiliary carcinoma after initiation by diethyl-nitrosamine (DEN). Here we show that alcohol-fed DEN-injected mice have higher ALT and liver-to-body weight ratio compared to pair-fed DEN-injected mice. Alcohol feeding results in steatohepatitis indicated by increased pro inflammatory cytokines and fibrotic genes. MRI and liver histology of alcohol+DEN mice shows hepatobiliary cysts, early hepatic neoplasia and increase in serum alpha-fetoprotein. Proliferation makers (BrdU, cyclin D1, p53) and cancer stem cell markers (CD133 and nanog) are significantly up-regulated in livers of alcohol-fed DEN-injected mice compared to controls. In livers with tumors, loss of miR-122 expression with a significant up-regulation of miR-122 target HIF 1alpha is seen. We conclude that alcoholic steatohepatitis accelerates hepatobiliary tumors with characteristic molecular features of HCC by up regulating inflammation, cell proliferation, stemness, and miR-122 loss. PMID- 26888604 TI - A novel transcription factor gene FHS1 is involved in the DNA damage response in Fusarium graminearum. AB - Cell cycle regulation and the maintenance of genome integrity are crucial for the development and virulence of the pathogenic plant fungus Fusarium graminearum. To identify transcription factors (TFs) related to these processes, four DNA damaging agents were applied to screen a F. graminearum TF mutant library. Sixteen TFs were identified to be likely involved in DNA damage responses. Fhs1 is a fungal specific Zn(II)2Cys6 TF that localises exclusively to nuclei. fhs1 deletion mutants were hypersensitive to hydroxyurea and defective in mitotic cell division. Moreover, deletion of FHS1 resulted in defects in perithecia production and virulence and led to the accumulation of DNA damage. Our genetic evidence demonstrated that the FHS1-associated signalling pathway for DNA damage response is independent of the ATM or ATR pathways. This study identified sixteen genes involved in the DNA damage response and is the first to characterise the novel transcription factor gene FHS1, which is involved in the DNA damage response. The results provide new insights into mechanisms underlying DNA damage responses in fungi, including F. graminearum. PMID- 26888607 TI - TRPV-1-mediated elimination of residual iPS cells in bioengineered cardiac cell sheet tissues. AB - The development of a suitable strategy for eliminating remaining undifferentiated cells is indispensable for the use of human-induced pluripotent stem (iPS) cell derived cells in regenerative medicine. Here, we show for the first time that TRPV-1 activation through transient culture at 42 degrees C in combination with agonists is a simple and useful strategy to eliminate iPS cells from bioengineered cardiac cell sheet tissues. When human iPS cells were cultured at 42 degrees C, almost all cells disappeared by 48 hours through apoptosis. However, iPS cell-derived cardiomyocytes and fibroblasts maintained transcriptional and protein expression levels, and cardiac cell sheets were fabricated after reducing the temperature. TRPV-1 expression in iPS cells was upregulated at 42 degrees C, and iPS cell death at 42 degrees C was TRPV-1 dependent. Furthermore, TRPV-1 activation through thermal or agonist treatment eliminated iPS cells in cardiac tissues for a final concentration of 0.4% iPS cell contamination. These findings suggest that the difference in tolerance to TRPV-1 activation between iPS cells and iPS cell-derived cardiac cells could be exploited to eliminate remaining iPS cells in bioengineered cell sheet tissues, which will further reduce the risk of tumour formation. PMID- 26888609 TI - Fatal rhabdomyolysis after torture by reverse hanging. AB - PURPOSE: Reverse hanging (also known as Palestinian hanging) is a form of positional torture where the victim is suspended for a prolonged period of time by the wrists, after the wrists are bound at the back. We report the first autopsy case of reverse hanging. We have discovered that fatal myoglobinuric renal failure due to rhabdomyolysis can be a complication of Palestinian hanging. METHOD: An adult detainee, who underwent interrogation by authorities, was admitted to hospital from a prison and died in hospital after a few days. Death was due to myoglobinuric renal failure. An autopsy was performed. RESULTS: At autopsy, the body showed anasarca due to renal failure. There were healing ligature marks on the wrist and forearm, but no blunt impact injury to the shoulders or arms. There was extensive necrosis of the pectoralis major, biceps, and deltoid muscles, organizing hemoarthrosis of the right glenohumeral joint and hemorrhage into the joint capsule of the both glenohumeral joints. The kidneys showed evidence of myoglobin deposition grossly. The overstretching of the major muscles of the shoulder, in response to the prolonged Palestinian hanging, gave rise to the muscle necrosis. CONCLUSION: This case underscores the importance of conducting autopsies on people who die in custody, particularly if detained at times of political instability when torture may be practiced by state actors and others. This case also reveals that fatal rhabdomyolysis can occur by positional torture in a stress position, despite the absence of direct trauma due to blunt impacts. PMID- 26888608 TI - A tRNA methyltransferase paralog is important for ribosome stability and cell division in Trypanosoma brucei. AB - Most eukaryotic ribosomes contain 26/28S, 5S, and 5.8S large subunit ribosomal RNAs (LSU rRNAs) in addition to the 18S rRNA of the small subunit (SSU rRNA). However, in kinetoplastids, a group of organisms that include medically important members of the genus Trypanosoma and Leishmania, the 26/28S large subunit ribosomal RNA is uniquely composed of 6 rRNA fragments. In addition, recent studies have shown the presence of expansion segments in the large ribosomal subunit (60S) of Trypanosoma brucei. Given these differences in structure, processing and assembly, T. brucei ribosomes may require biogenesis factors not found in other organisms. Here, we show that one of two putative 3-methylcytidine methyltransferases, TbMTase37 (a homolog of human methyltransferase-like 6, METTL6), is important for ribosome stability in T. brucei. TbMTase37 localizes to the nucleolus and depletion of the protein results in accumulation of ribosomal particles lacking srRNA 4 and reduced levels of polysome associated ribosomes. We also find that TbMTase37 plays a role in cytokinesis, as loss of the protein leads to multi-flagellated and multi-nucleated cells. PMID- 26888610 TI - Meningiomas in three male-to-female transgender subjects using oestrogens/progestogens and review of the literature. AB - Sex hormones have been proposed as a possible risk factor for the development and growth of meningiomas. Hormonal therapy plays a fundamental role in the treatment of male-to-female transgenders and needs to be continued after sex reassignment surgery. Usually, this treatment leads to no adverse events; however, its impact on hormone-related tumours such as meningiomas has not yet been investigated thoroughly. We searched our cohort of 2810 male-to-female transgender persons, who have been treated between 1975 and 2010, for patients with meningiomas. Additionally, we conducted a literature search in PubMed and EMBASE. We found three patients who developed a meningioma in male-to-female transgenders in addition to five other who have been described in the literature. These findings support the role of female sex hormones in the development and growth of meningiomas. This might be an underrepresentation, because there is no standard protocol for screening for meningiomas in this population and meningiomas can remain asymptomatic for several years. We observed regression of multiple meningiomas in one of these three cases after discontinuation of hormonal treatment. The decision to stop or continue cross-sex hormone therapy in these particular patients should be carefully reconsidered individually. PMID- 26888613 TI - Measuring Cortical Connectivity in Alzheimer's Disease as a Brain Neural Network Pathology: Toward Clinical Applications. AB - OBJECTIVES: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of Alzheimer's disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity underlying human cognition. METHODS: We reviewed papers registered in PubMed and other scientific repositories on the use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to cognitively intact elderly individuals (Controls). RESULTS: Hundreds of peer-reviewed (cross sectional and longitudinal) papers have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic, and anterior-posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited. CONCLUSIONS: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD. PMID- 26888614 TI - Imaging the "At-Risk" Brain: Future Directions. AB - OBJECTIVES: Clinical neuroscience is increasingly turning to imaging the human brain for answers to a range of questions and challenges. To date, the majority of studies have focused on the neural basis of current psychiatric symptoms, which can facilitate the identification of neurobiological markers for diagnosis. However, the increasing availability and feasibility of using imaging modalities, such as diffusion imaging and resting-state fMRI, enable longitudinal mapping of brain development. This shift in the field is opening the possibility of identifying predictive markers of risk or prognosis, and also represents a critical missing element for efforts to promote personalized or individualized medicine in psychiatry (i.e., stratified psychiatry). METHODS: The present work provides a selective review of potentially high-yield populations for longitudinal examination with MRI, based upon our understanding of risk from epidemiologic studies and initial MRI findings. RESULTS: Our discussion is organized into three topic areas: (1) practical considerations for establishing temporal precedence in psychiatric research; (2) readiness of the field for conducting longitudinal MRI, particularly for neurodevelopmental questions; and (3) illustrations of high-yield populations and time windows for examination that can be used to rapidly generate meaningful and useful data. Particular emphasis is placed on the implementation of time-appropriate, developmentally informed longitudinal designs, capable of facilitating the identification of biomarkers predictive of risk and prognosis. CONCLUSIONS: Strategic longitudinal examination of the brain at-risk has the potential to bring the concepts of early intervention and prevention to psychiatry. PMID- 26888611 TI - Modern Methods for Interrogating the Human Connectome. AB - OBJECTIVES: Connectionist theories of brain function took hold with the seminal contributions of Norman Geschwind a half century ago. Modern neuroimaging techniques have expanded the scientific interest in the study of brain connectivity to include the intact as well as disordered brain. METHODS: In this review, we describe the most common techniques used to measure functional and structural connectivity, including resting state functional MRI, diffusion MRI, and electroencephalography and magnetoencephalography coherence. We also review the most common analytical approaches used for examining brain interconnectivity associated with these various imaging methods. RESULTS: This review presents a critical analysis of the assumptions, as well as methodological limitations, of each imaging and analysis approach. CONCLUSIONS: The overall goal of this review is to provide the reader with an introduction to evaluating the scientific methods underlying investigations that probe the human connectome. PMID- 26888615 TI - Variation in White Matter Connectivity Predicts the Ability to Remember Faces and Discriminate Their Emotions. AB - OBJECTIVES: The extended face network contains clusters of neurons that perform distinct functions on facial stimuli. Regions in the posterior ventral visual stream appear to perform basic perceptual functions on faces, while more anterior regions, such as the ventral anterior temporal lobe and amygdala, function to link mnemonic and affective information to faces. Anterior and posterior regions are interconnected by a long-range white matter tracts; however, it is not known if variation in connectivity of these pathways explains cognitive performance. METHODS: Here, we used diffusion imaging and deterministic tractography in a cohort of 28 neurologically normal adults ages 18-28 to examine microstructural properties of visual fiber pathways and their relationship to certain mnemonic and affective functions involved in face processing. We investigated how inter individual variability in two tracts, the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), related to performance on tests of facial emotion recognition and face memory. RESULTS: Results revealed that microstructure of both tracts predicted variability in behavioral performance indexed by both tasks, suggesting that the ILF and IFOF play a role in facilitating our ability to discriminate emotional expressions in faces, as well as to remember unique faces. Variation in a control tract, the uncinate fasciculus, did not predict performance on these tasks. CONCLUSIONS: These results corroborate and extend the findings of previous neuropsychology studies investigating the effects of damage to the ILF and IFOF, and demonstrate that differences in face processing abilities are related to white matter microstructure, even in healthy individuals. PMID- 26888612 TI - Traumatic Brain Injury as a Disorder of Brain Connectivity. AB - OBJECTIVES: Recent advances in neuroimaging methodologies sensitive to axonal injury have made it possible to assess in vivo the extent of traumatic brain injury (TBI) -related disruption in neural structures and their connections. The objective of this paper is to review studies examining connectivity in TBI with an emphasis on structural and functional MRI methods that have proven to be valuable in uncovering neural abnormalities associated with this condition. METHODS: We review studies that have examined white matter integrity in TBI of varying etiology and levels of severity, and consider how findings at different times post-injury may inform underlying mechanisms of post-injury progression and recovery. Moreover, in light of recent advances in neuroimaging methods to study the functional connectivity among brain regions that form integrated networks, we review TBI studies that use resting-state functional connectivity MRI methodology to examine neural networks disrupted by putative axonal injury. RESULTS: The findings suggest that TBI is associated with altered structural and functional connectivity, characterized by decreased integrity of white matter pathways and imbalance and inefficiency of functional networks. These structural and functional alterations are often associated with neurocognitive dysfunction and poor functional outcomes. CONCLUSIONS: TBI has a negative impact on distributed brain networks that lead to behavioral disturbance. PMID- 26888618 TI - Altered Effective Connectivity during a Processing Speed Task in Individuals with Multiple Sclerosis. AB - OBJECTIVES: Processing speed impairment is the most prevalent cognitive deficit in individuals with multiple sclerosis (MS). However, the neural mechanisms associated with processing speed remain under debate. The current investigation provides a dynamic representation of the functioning of the brain network involved in processing speed by examining effective connectivity pattern during a processing speed task in healthy adults and in MS individuals with and without processing speed impairment. METHODS: Group assignment (processing speed impaired vs. intact) was based on participants' performance on the Symbol Digit Modalities test (Parmenter, Testa, Schretlen, Weinstock-Guttman, & Benedict, 2010). First, brain regions involved in the processing speed task were determined in healthy participants. Time series from these functional regions of interest of each group of participants were then subjected to the effective connectivity analysis (Independent Multiple-Sample Greedy Equivalence Search and Linear, Non-Gaussian Orientation, Fixed Structure algorithms) that showed causal influences of one region on another during task performance. RESULTS: The connectivity pattern of the processing speed impaired group was significantly different from the connectivity pattern of the processing speed intact group and of the healthy control group. Differences in the strength of common connections were also observed. CONCLUSIONS: Effective connectivity results reveal that MS individuals with processing speed impairment not only have connections that differ from healthy participants and MS individuals without processing speed impairment, but also have increased strengths of connections. PMID- 26888617 TI - Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease. AB - OBJECTIVES: Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. METHODS: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. RESULTS: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. CONCLUSIONS: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease. PMID- 26888616 TI - Fornix Microstructure and Memory Performance Is Associated with Altered Neural Connectivity during Episodic Recognition. AB - OBJECTIVES: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task related connectivity during episodic recognition. METHODS: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer's Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. RESULTS: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. CONCLUSIONS: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain-at least in part-connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. PMID- 26888619 TI - Differential Resting State Connectivity Patterns and Impaired Semantically Cued List Learning Test Performance in Early Course Remitted Major Depressive Disorder. AB - OBJECTIVES: There is a well-known association between memory impairment and major depressive disorder (MDD). Additionally, recent studies are also showing resting state functional magnetic resonance imaging (rsMRI) abnormalities in active and remitted MDD. However, no studies to date have examined both rs connectivity and memory performance in early course remitted MDD, nor the relationship between connectivity and semantically cued episodic memory. METHODS: The rsMRI data from two 3.0 Tesla GE scanners were collected from 34 unmedicated young adults with remitted MDD (rMDD) and 23 healthy controls (HCs) between 18 and 23 years of age using bilateral seeds in the hippocampus. Participants also completed a semantically cued list-learning test, and their performance was correlated with hippocampal seed-based rsMRI. Regression models were also used to predict connectivity patterns from memory performance. RESULTS: After correcting for sex, rMDD subjects performed worse than HCs on the total number of words recalled and recognized. rMDD demonstrated significant in-network hypoactivation between the hippocampus and multiple fronto-temporal regions, and multiple extra-network hyperconnectivities between the hippocampus and fronto-parietal regions when compared to HCs. Memory performance negatively predicted connectivity in HCs and positively predicted connectivity in rMDD. Conclusions Even when individuals with a history of MDD are no longer displaying active depressive symptoms, they continue to demonstrate worse memory performance, disruptions in hippocampal connectivity, and a differential relationship between episodic memory and hippocampal connectivity. PMID- 26888620 TI - Graph Metrics of Structural Brain Networks in Individuals with Schizophrenia and Healthy Controls: Group Differences, Relationships with Intelligence, and Genetics. AB - OBJECTIVES: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. METHODS: Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. RESULTS: The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity--connections among high degree "rich club" nodes, "feeder" connections to these rich club nodes, and "local" connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. CONCLUSIONS: Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA. PMID- 26888621 TI - Brain Network Organization and Social Executive Performance in Frontotemporal Dementia. AB - OBJECTIVES: Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance. METHODS: Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures. RESULTS: Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate. CONCLUSIONS: bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile. PMID- 26888623 TI - The Lack of Lutein Accelerates the Extent of Light-induced Bleaching of Photosynthetic Pigments in Thylakoid Membranes of Arabidopsis thaliana. AB - The high light-induced bleaching of photosynthetic pigments and the degradation of proteins of light-harvesting complexes of PSI and PSII were investigated in isolated thylakoid membranes of Arabidopsis thaliana, wt and lutein-deficient mutant lut2, with the aim of unraveling the role of lutein for the degree of bleaching and degradation. By the means of absorption spectroscopy and western blot analysis, we show that the lack of lutein leads to a higher extent of pigment photobleaching and protein degradation in mutant thylakoid membranes in comparison with wt. The highest extent of bleaching is suffered by chlorophyll a and carotenoids, while chlorophyll b is bleached in lut2 thylakoids during long periods at high illumination. The high light-induced degradation of Lhca1, Lhcb2 proteins and PsbS was followed and it is shown that Lhca1 is more damaged than Lhcb2. The degradation of analyzed proteins is more pronounced in lut2 mutant thylakoid membranes. The lack of lutein influences the high light-induced alterations in organization of pigment-protein complexes as revealed by 77 K fluorescence. PMID- 26888622 TI - Disrupted Intrinsic Connectivity among Default, Dorsal Attention, and Frontoparietal Control Networks in Individuals with Chronic Traumatic Brain Injury. AB - OBJECTIVES: Individuals with chronic traumatic brain injury (TBI) often show detrimental deficits in higher order cognitive functions requiring coordination of multiple brain networks. Although assessing TBI-related deficits in higher order cognition in the context of network dysfunction is promising, few studies have systematically investigated altered interactions among multiple networks in chronic TBI. METHOD: We characterized disrupted resting-state functional connectivity of the default mode network (DMN), dorsal attention network (DAN), and frontoparietal control network (FPCN) whose interactions are required for internally and externally focused goal-directed cognition in chronic TBI. Specifically, we compared the network interactions of 40 chronic TBI individuals (8 years post-injury on average) with those of 17 healthy individuals matched for gender, age, and years of education. RESULTS: The network-based statistic (NBS) on DMN-DAN-FPCN connectivity of these groups revealed statistically significant (p NBS2.58) reductions in within-DMN, within-FPCN, DMN-DAN, and DMN-FPCN connectivity of the TBI group over healthy controls. Importantly, such disruptions occurred prominently in between-network connectivity. Subsequent analyses further exhibited the disrupted connectivity patterns of the chronic TBI group occurring preferentially in long-range and inter-hemispheric connectivity of DMN-DAN-FPCN. Most importantly, graph-theoretic analysis demonstrated relative reductions in global, local and cost efficiency (p<.05) as a consequence of the network disruption patterns in the TBI group. CONCLUSION: Our findings suggest that assessing multiple networks-of-interest simultaneously will allow us to better understand deficits in goal-directed cognition and other higher order cognitive phenomena in chronic TBI. Future research will be needed to better understand the behavioral consequences related to these network disruptions. PMID- 26888625 TI - Association of lipid profile with serum PON1 concentration in patients with chronic kidney disease. AB - Patients with chronic kidney disease (CKD) are at high risk of atherosclerotic events; dyslipoproteinemia and the decrease of the HDL-linked enzyme paraoxonase 1 (PON1), might have a major role. This study intends to compare the association between lipid profile and serum PON1 levels in renal failure (RF) and hemodialysis (HD) patients. Serum lipids, HDL-subclasses and PON1 concentration were evaluated in 90 patients with CKD, divided into groups: RF (n = 46) and HD (n = 44), and in 30 normal individuals (control group). The results showed that PON1 was significantly lower in HD patients than in RF and controls (p < 0.001). In RF patients under statin therapy, PON1 did not differ from that of patients without statins. In HD patients without statins, PON1 was considerably low, whereas in HD with statins (30.42 +/- 12.62 MUg/mL) was lower than RF with statins (49.31 +/- 14.94, p < 0.001). PON1 concentration was significantly and positively associated with HDL-C, HDL3-C and Apo A1 in all groups. Additionally, in HD patients PON1 was negatively associated with LDL-C. Multiple regression analysis revealed that LDL-C and statin treatment were independently related to PON1 concentration in HD patients (beta = -0.331, p = 0.026 and beta = 0.344, p = 0.020, respectively). In RF patients, HDL3-C and Apo A1 are strong determinants of PON1 levels. It is concluded that different parameters of lipid profile seem to affect serum PON1 concentration of RF and HD patients and probably contribute to the delay of atherosclerosis. PMID- 26888624 TI - Ethnic Disparities in the Onset and Progression of Functional Limitations Among Israeli Middle-Aged and Older Adults: Socioeconomic and Health-Related Pathways. AB - OBJECTIVE: To examine whether socioeconomic and health-related factors explain ethnic disparities in the onset and progression of functional limitations among middle-aged and older Israeli adults. METHOD: We used data from Waves I-III of the Survey of Health, Aging and Retirement in Europe in Israel. Logistic and multinomial regression models were estimated to examine the association between ethnicity and transitions in functional status (onset versus progression) from respondents' baseline interview (Wave I or II) to their follow-up interview (Wave II or III). RESULTS: Compared to veteran Jews, Arabs and Jewish immigrants from the former Soviet Union were more likely to experience an onset of functional limitations. Arabs were also more likely to experience worsening functional limitations by follow-up. Education and health-related factors attenuated some of the ethnic disparities in onset and progression of functional limitations. CONCLUSIONS: Our findings suggest the importance of moving beyond traditional indicators of socioeconomic status and health-related pathways to fully understand the underlying factors that predict ethnic disparities in the onset and progression of functional limitations in Israel. PMID- 26888626 TI - Change in CD3zeta-chain expression is an independent predictor of disease status in head and neck cancer patients. AB - CD3zeta has emerged as a clinically important immunological marker in head and neck squamous cell carcinoma (HNSCC) with reduced level of expression reported in both tumor infiltrating lymphocytes and peripheral blood lymphocytes. In this prospective study (power = 0.99, alpha = 0.05), CD3zeta expression was compared in 47 HNSCC patients and 53 controls using standardized flow cytometric method. There was no statistical difference in the percentages of the CD3 epsilon+ T-cell subset present in the peripheral blood mononuclear cells of the HNSCC patients and the healthy controls; however, T cells from the HNSCC patients produced a significantly weaker IFN-gamma response in comparison to the healthy controls, when they were stimulated by the recall viral CEF peptide antigen. All patients were followed up for at least 3 years with a median follow-up of 45 months. Levels of CD3zeta-chain expression were measured at 117 follow-up visits at six month intervals. Receiver operating characteristic curve identified the optimal cut off as a 12% increase in post treatment CD3zeta-chain expression from the baseline levels to confirm absence of HNSCC with the area under curve of 0.81 (95% CI = 0.68-0.94) for predicting absence of HNSCC. The specificity, sensitivity and positive predictive value were 81.25% 79.21% and 97.56%, respectively. Three-year disease specific survival (DSS) was significantly lower (p = 0.007) at 63.2% for patients who showed <12% increase in CD3zeta-chain level as compared to 96.2% for patients who had >=12% increase. Our results indicate that the change in CD3zeta-chain expression from the baseline is an independent predictor of residual and recurrent HNSCC. PMID- 26888627 TI - Dnd knockout ablates germ cells and demonstrates germ cell independent sex differentiation in Atlantic salmon. AB - Introgression of farmed salmon escapees into wild stocks is a major threat to the genetic integrity of wild populations. Using germ cell-free fish in aquaculture may mitigate this problem. Our study investigated whether it is possible to produce germ cell-free salmon in F0 by using CRISPR-Cas9 to knock out dnd, a factor required for germ cell survival in vertebrates. To avoid studying mosaic animals, sgRNA targeting alb was simultaneously used as a visual tracer since the phenotype of alb KO is complete loss of pigmentation. Induced mutations for the tracer (alb) and the target (dnd) genes were highly correlated and produced germ cell-less fish lacking pigmentation, underlining the suitability of alb KO to serve as tracer for targeted double allelic mutations in F0 animals in species with prohibitively long generation times. This is also the first report describing dnd knockout in any fish species. Analyzing gene expression and histology of dnd KO fish revealed that sex differentiation of the somatic compartment does not depend on the presence of germ cells. However, the organization of the ovarian somatic compartment seems compromised in mutant fish. PMID- 26888628 TI - Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes. AB - OBJECTIVE: To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). DESIGN: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naive at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. METHODS: Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). RESULTS: MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. CONCLUSIONS: MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD. PMID- 26888629 TI - Low beta-arrestin expression correlates with the responsiveness to long-term somatostatin analog treatment in acromegaly. AB - OBJECTIVE: The high expression of somatostatin receptor subtype 2 (SSTR2 also known as sst2) usually present in growth hormone (GH)-secreting adenomas is the rationale for therapy with somatostatin analogs (SSAs) in acromegaly. Although SSTR2 expression is a good predictor for biochemical response to SSA treatment, we still face tumors resistant to SSAs despite high SSTR2 expression. Recently, beta-arrestins (beta-arrestins) have been highlighted as key players in the regulation of SSTR2 function. DESIGN: To investigate whether beta-arrestins might be useful predictors of responsiveness to long-term SSA treatment in acromegaly, we retrospectively evaluated 35 patients with acromegaly who underwent adenomectomy in two referral centers in The Netherlands. METHODS: beta-arrestin mRNA levels were evaluated in adenoma samples, together with SSTR2 (and SSTR5) mRNA and protein expression. Biochemical response to long-term SSA treatment (median 12 months) was assessed in 32 patients. RESULTS: beta-arrestin 1 and 2 mRNA was significantly lower in adenoma tissues from patients who achieved insulin-like growth factor 1 normalization (P = 0.024 and P = 0.047) and complete biochemical control (P = 0.047 and P = 0.039). The SSTR2 mRNA was higher in SSA responder patients compared with the resistant ones (P = 0.026). This difference was more evident when analyzing the SSTR2/beta-arrestin 1 and SSTR2/beta-arrestin 2 ratio (P = 0.011 and P = 0.010). beta-arrestin 1 and 2 expression showed a significant trend of higher median values from full responders, partial responders to resistant patients (P = 0.045 and P = 0.021, respectively). Interestingly, SSTR2 protein expression showed a strong inverse correlation with both beta-arrestin 1 and 2 mRNA (rho = -0.69, P = 0.0011 and rho = -0.67, P = 0.0016). CONCLUSIONS: Low beta-arrestin expression and high SSTR2/beta-arrestin ratio correlate with the responsiveness to long-term treatment with SSAs in patients with acromegaly. PMID- 26888631 TI - The effect of cadence on the muscle-tendon mechanics of the gastrocnemius muscle during walking. AB - Humans naturally select a cadence that minimizes metabolic cost at a constant walking velocity. The aim of this study was to examine the effects of cadence on the medial gastrocnemius (MG) muscle and tendon interaction, and examine how this might influence lower limb energetics. We hypothesized that cadences higher than preferred would increase MG fascicle shortening velocity because of the reduced stride time. Furthermore, we hypothesized that cadences lower than preferred would require greater MG fascicle shortening to achieve increased muscle work requirements. We measured lower limb kinematics and kinetics, surface electromyography of the triceps surae and MG fascicle length, via ultrasonography, during walking at a constant velocity at the participants' preferred cadence and offsets of +/-10%, +/-20%, and +/-30%. There was a significant increase in MG fascicle shortening with decreased cadence. However, there was no increase in the MG fascicle shortening velocity at cadences higher than preferred. Cumulative MG muscle activation per minute was significantly increased at higher cadences. We conclude that low cadence walking requires more MG shortening work, while MG muscle and tendon function changes little for each stride at higher cadences, driving up cumulative activation costs due to the increase in steps per minute. PMID- 26888630 TI - Impact of chemical structure of flavanol monomers and condensed tannins on in vitro anthelmintic activity against bovine nematodes. AB - Plants containing condensed tannins (CT) may have potential to control gastrointestinal nematodes (GIN) of cattle. The aim was to investigate the anthelmintic activities of four flavan-3-ols, two galloyl derivatives and 14 purified CT fractions, and to define which structural features of CT determine the anti-parasitic effects against the main cattle nematodes. We used in vitro tests targeting L1 larvae (feeding inhibition assay) and adults (motility assay) of Ostertagia ostertagi and Cooperia oncophora. In the larval feeding inhibition assay, O. ostertagi L1 were significantly more susceptible to all CT fractions than C. oncophora L1. The mean degree of polymerization of CT (i.e. average size) was the most important structural parameter: large CT reduced larval feeding more than small CT. The flavan-3-ols of prodelphinidin (PD)-type tannins had a stronger negative influence on parasite activity than the stereochemistry, i.e. cis- vs trans-configurations, or the presence of a gallate group. In contrast, for C. oncophora high reductions in the motility of larvae and adult worms were strongly related with a higher percentage of PDs within the CT fractions while there was no effect of size. Overall, the size and the percentage of PDs within CT seemed to be the most important parameters that influence anti-parasitic activity. PMID- 26888632 TI - Clinical Outcomes of Implants Placed in Extraction Sockets and Immediately Restored: A 7-Year Single-Cohort Prospective Study. AB - BACKGROUND: The placement of implants immediately after tooth extraction has proven to be a predictable treatment strategy with a very high success rate. PURPOSE: The aim of the present 7-year prospective single cohort study was to evaluate the success rate, marginal bone level (MBL), soft tissue stability of implants placed in fresh extraction sockets and immediately restored. MATERIAL AND METHODS: This prospective cohort study included 37 implants in 32 patients (19 females and 13 males) with an average age of 40.1 +/- 13.3 (range: 21-63 years) who received immediate implants and immediate single unit restorations. Outcome evaluations were: implant failures, complications, MBL, width of keratinized gingiva, facial soft tissue (FST) levels, modified Plaque Index and modified Bleeding Index. RESULTS AND CONCLUSIONS: The cumulative survival rate was of 94.6% at 7-year visit. The mean MBL was -0.6 +/- 0.49 mm at baseline and 1 +/- 0.2 mm after 7 years. The FST Level was 0.4 +/- 0.69 mm at baseline and 0.02 +/- 0.70 mm at the 7-year follow-up. The Width of Keratinazed Gingiva was 3.8 +/- 0.47 mm at baseline and 3.1 +/- 0.42 mm at 7-year follow-up. Implants placed immediately after tooth extraction and immediately restored showed predictable clinical outcomes in this prospective study. PMID- 26888633 TI - Shade-induced stem elongation in rice seedlings: Implication of tissue-specific phytohormone regulation. AB - A better understanding of shade avoidance syndrome (SAS) is an urgent need because of its effect on energy reallocation. Leverage-related mechanism in crops is of potential economic interest for agricultural applications. Here we report the SAS phenotype at tissue level rice seedlings. Tissue-specific RNA-sequencing indicates auxin plays different roles between coleoptile and the first leaf. Phenotypes of wild type treated by gibberellin and brassinosteroid biosynthesis inhibitors and of related mutants suggest these two hormones positively regulate SAS. Our work reveals the diversity of hormone responses in different organs and different species in shade conditions. PMID- 26888635 TI - Two-dimensional correlation infrared spectroscopy applied to the identification of ephedrine and pseudoephedrine in illegally adulterated slimming herbal products. AB - Two-dimensional correlation spectroscopy (2DCOS) was employed for the identification of ephedrine (Ep) and pseudoephedrine (Ps) present in illegally adulterated slimming herbal products (SHPs). Second derivative (SD) spectral pretreatment was used prior to 2DCOS analysis to highlight specific features not readily observable by Fourier transform infrared spectroscopy (FTIR), SD-FTIR, or original 2DCOS, leading to enhanced resolution and a reduced lower limit of detection (<1% in this study). After examining the power spectra of suspicious SHPs, bands containing characteristic peaks for Ep (701, 747, 1042, 1363, 1375, 1451, 1478 cm-1 etc) and/or Ps (703, 767, 1037, 1375, 1428, 1455, 1590 cm- 1, etc.) were selected to construct synchronous and asynchronous maps for further analysis, while the latter was applied to discriminate positive SHPs adulterated simultaneously with Ep and Ps. The proposed method is simple and economical and has the potential to identify other chemicals in illegally adulterated herbal products. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888634 TI - Abnormal tau induces cognitive impairment through two different mechanisms: synaptic dysfunction and neuronal loss. AB - The hyperphosphorylated microtubule-associated protein tau is present in several neurodegenerative diseases, although the causal relationship remains elusive. Few mouse models used to study Alzheimer-like dementia target tau phosphorylation. We created an inducible pseudophosphorylated tau (Pathological Human Tau, PH-Tau) mouse model to study the effect of conformationally modified tau in vivo. Leaky expression resulted in two levels of PH-Tau: low basal level and higher upon induction (4% and 14% of the endogenous tau, respectively). Unexpectedly, low PH Tau resulted in significant cognitive deficits, decrease in the number of synapses (seen by EM in the CA1 region), reduction of synaptic proteins, and localization to the nucleus. Induction of PH-Tau triggered neuronal death (60% in CA3), astrocytosis, and loss of the processes in CA1. These findings suggest, that phosphorylated tau is sufficient to induce neurodegeneration and that two different mechanisms can induce cognitive impairment depending on the levels of PH-Tau expression. PMID- 26888637 TI - Erratum to: Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers. AB - In the article entitled: "Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers" published in the January 2016 issue of theJournal, Can J Anesth 2016; 63: 24-30, in the second column of page 29, the second to last sentence of the first paragraph should read: "Another study by Sorenson et al. examined 15 healthy males under different physiologic conditions". The publisher apologizes most sincerely for this error. PMID- 26888638 TI - A modified device for removing large regurgitation volume during tracheal intubation. PMID- 26888636 TI - Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies. AB - RATIONALE: Cardiac stem cells (CSC) therapy has been clinically introduced for cardiac repair after myocardial infarction (MI). To date, there has been no systematic overview and meta-analysis of studies using CSC therapy for MI. OBJECTIVE: Here, we used meta-analysis to establish the overall effect of CSCs in preclinical studies and assessed translational differences between and within large and small animals in the CSC therapy field. In addition, we explored the effect of CSC type and other clinically relevant parameters on functional outcome to better predict and design future (pre)clinical studies using CSCs for MI. METHODS AND RESULTS: A systematic search was performed, yielding 80 studies. We determined the overall effect of CSC therapy on left ventricular ejection fraction and performed meta-regression to investigate clinically relevant parameters. We also assessed the quality of included studies and possible bias. The overall effect observed in CSC-treated animals was 10.7% (95% confidence interval 9.4-12.1; P<0.001) improvement in ejection fraction compared with placebo controls. Interestingly, CSC therapy had a greater effect in small animals compared with large animals (P<0.001). Meta-regression indicated that cell type was a significant predictor for ejection fraction improvement in small animals. Minor publication bias was observed in small animal studies. CONCLUSIONS: CSC treatment resulted in significant improvement of ejection fraction in preclinical animal models of MI compared with placebo. There was a reduction in the magnitude of effect in large compared with small animal models. Although different CSC types have overlapping culture characteristics, we observed a significant difference in their effect in post-MI animal studies. PMID- 26888640 TI - Estimation of NMVOC emissions using artificial neural networks and economical and sustainability indicators as inputs. AB - This paper describes the development of an artificial neural network (ANN) model based on economical and sustainability indicators for the prediction of annual non-methane volatile organic compounds (NMVOCs) emissions in China for the period 2005-2011 and its comparison with inventory emission factor models. The NMVOCs emissions in China were estimated using ANN model which was created using available data for nine European countries, which NMVOC emission per capita approximately correspond to the Chinese emissions, for the period 2004-2012. The forward input selection strategy was used to compare the significance of particular inputs for the prediction of NMVOC emissions in the nine selected EU countries and China. The final ANN model was trained using only five input variables, and it has demonstrated similar accuracy in predicting NMVOC emissions for the selected EU countries that were used for the development of the model and then for China for which the input dataset was previously unknown to the ANN model. The obtained mean absolute percentage error (MAPE) values were 8 % for EU countries and 5 % for China. Also, the temporal trend of NMVOC emissions predicted in this study is generally consistent with the trend obtained using inventory emission models. The proposed ANN approach can represent a viable alternative for the prediction of NMVOC emissions at the national level, in particular for developing countries which are usually lacking emission data. PMID- 26888639 TI - The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to HIV-1 infection in the Polish population. AB - Killer cell immunoglobulin-like receptors (KIR) are the most polymorphic receptors of natural killer (NK) cells. Their activity diversifies the functions of NK cells in the antiviral immune response, so the presence of certain KIR may affect transmission of HIV-1. The aim of the study was to evaluate the influence of KIR genes on the susceptibility to HIV-1 infection in the Polish population depending on the route of exposure. We determined the frequencies of activating (2DS1, 2DS2, 2DS3, 2DS4f, 2DS4del, 2DS5, 3DS1) and inhibitory (2DL1, 2DL2, 2DL3, 2DL5, 3DL1) KIRs in HIV-1-positive patients (n = 459), individuals exposed to HIV 1 but uninfected (EU, n = 118) and in uninfected, healthy blood donors (BD, n = 98). Analysis was performed using stepwise logistic regression. Apart from KIRs, CCR5-?32, and CCR2-64I, alleles were also analyzed, as we knew or suspected that these features could affect susceptibility to HIV infection. The regression confirmed the protective effect of CCR5-?32 (OR = 0.25, p = 0.006) and CCR2-64I (OR = 0.59, p = 0.032) against HIV infection. Among KIR genes, 2DL3 was found to be a protective factor (OR = 0.30, p = 0.015). A similar effect was seen for 3DS1 but only in intravenous drug users (IDUs) (OR = 0.30, p = 0.019), not in sexually exposed people. 2DL5 was found to be a factor facilitating HIV infection (OR = 2.13, p = 0.013). A similar effect was observed for 2DL2 but only in females (OR = 2.15, p = 0.040), and 2DS1 in IDUs (OR = 3.03, p = 0.022). Our results suggest a beneficial role of KIR3DS1 and 2DL3 supporting resistance to HIV infection and a harmful effect of 2DS1, 2DL5, and 2DL2 genes promoting HIV acquisition. PMID- 26888641 TI - Comparison of the chemical, physical and microbial properties of composts produced by conventional composting or vermicomposting using the same feedstocks. AB - The chemical, physical and microbial properties of thermophilic composts and vermicomposts were compared using the same municipal green waste-based feedstocks: (i) municipal green waste alone, (ii) 75 % municipal green waste/25 % green garden waste and (iii) 75 % municipal green waste/25 % cattle manure. Temperatures reached 37 degrees C during composting of municipal green waste alone but when garden waste or cattle manure were added, temperatures reached 47 and 52 degrees C, respectively. At the end of vermicomposting (using Eisenia fetida), the number of earthworms present was greater than that added for the cattle manure-amended feedstock but much less for both the garden waste and municipal green waste alone treatments. The products formed in all treatments generally fell within suggested maturity indices for composts. Greater organic matter decomposition occurred during composting than vermicomposting resulting in composts having a significantly lower organic C content and a greater content of total N, extractable Mg, K, Na, P, and mineral N, a higher EC and a lower C/N ratio than the vermicomposts. For all three feedstocks, vermicomposts had a lower bulk density and greater total porosity and macroporosity than composts. For the garden waste- and cattle manure-amended feedstocks, vermicomposts had a higher microbial biomass C than the composts and for all three feedstocks, basal respiration and metabolic quotient were greatest for vermicomposts. It was concluded that composting is a robust process suitable for treatment of a range of organic wastes but, because of the nutritional requirements of the earthworms, vermicomposting is a much less robust and was only suitable for the cattle manure amended feedstock. PMID- 26888642 TI - Selenium catalyzed Fe(III)-EDTA reduction by Na2SO3: a reaction-controlled phase transfer catalysis. AB - Fe(II)-EDTA, a typical chelated iron, is able to coordinate with nitric oxide (NO) which accelerates the rates and kinetics of the absorption of flue gas. However, Fe(II)-EDTA can be easily oxidized to Fe(III)-EDTA which is unable to absorb NO. Therefore, the regeneration of fresh Fe(II)-EDTA, which actually is the reduction of Fe(III)-EDTA to Fe(II)-EDTA, becomes a crucial step in the denitrification process. To enhance the reduction rate of Fe(III)-EDTA, selenium was introduced into the SO3 (2-)/Fe(III)-EDTA system as catalyst for the first time. By comparison, the reduction rate was enhanced by four times after adding selenium even at room temperature (25 degrees C). Encouragingly, elemental Se could precipitate out when SO3 (2-) was consumed up by oxidation to achieve self separation. A catalysis mechanism was proposed with the aid of ultraviolet visible (UV-Vis) spectroscopy, Tyndall scattering, horizontal attenuated total reflection Fourier transform infrared (HATR-FTIR) spectroscopy, and X-ray diffraction (XRD). In the catalysis process, the interconversion between SeSO3 (2 ) and nascent Se formed a catalysis circle for Fe(III)-EDTA reduction in SO3 (2-) circumstance. PMID- 26888643 TI - Doctor-diagnosed health problems in a region with a high density of concentrated animal feeding operations: a cross-sectional study. AB - BACKGROUND: There is growing interest in health risks of residents living near concentrated animal feeding operations (CAFOs). Previous research mostly focused on swine CAFOs and self-reported respiratory conditions. The aim was to study the association between the presence of swine, poultry, cattle and goat CAFOs and health of Dutch neighbouring residents using electronic medical records from general practitioners (GPs). METHODS: Data for the year 2009 were collected of 119,036 inhabitants of a rural region with a high density of CAFOs using information from GIAB (high exposed population). A comparison was made with GP data from 78,060 inhabitants of rural areas with low densities of CAFOs (low exposed population). Associations between the number of CAFOs near residents' homes and morbidity were determined by multilevel (cross-classified) logistic regression. RESULTS: In 2009, the prevalence of most respiratory and gastrointestinal conditions was similar in the high and low exposed population. Exceptions were pneumonia, atopic eczema and unspecified infectious diseases with an increased prevalence, and sinusitis with a decreased prevalence in the high exposed population. Within the high CAFO density region, the number of poultry, cattle and swine CAFOs near residents' homes was not associated with allergic, respiratory or gastrointestinal conditions. Conversely, each additional goat CAFO within the postal code area of residents' homes significantly increased the odds of unspecified infectious disease and pneumonia by 87 and 41 percent, respectively. CONCLUSIONS: Using GP records, pneumonia and unspecified infectious diseases were positively associated with the number of goat CAFOs near residents' homes, but no association was found between swine, cattle, and poultry CAFOs and respiratory, allergic or gastrointestinal conditions. PMID- 26888645 TI - Inequalities in perceived health in the Russian Federation, 1994-2012. AB - BACKGROUND: Individual characteristics and socioeconomic strata (SES) are important determinants of health differences. We examine health inequalities in Russia and estimate the association of demography (gender and age) and SES (working status, income, geography of residence, living standard, wealth possession, and durable asset-holding) with perceived health over the period 1994 2012. METHODS: This study uses nationally representative datasets from the Russian Longitudinal Monitoring Survey (RLMS: 1994-2012). We apply a random effect GLS model to examine the association of individual characteristics and individual heterogeneity in explaining self-perceived health status. In addition, we estimate a regression-based concentration index, which we decompose into the determinants of health inequalities. RESULTS: The self-perceived health differences between the better-off and the worse-off is reduced over the 18 year period (1994 - 2012). The individual variances in self-perceived health status are higher compared to the variances between the individuals over the period. The measure of health inequality index (concentration index) indicates a change for better health for the better-off Russians. Being employed matters in perceiving a better health status for the Russians in 2012. CONCLUSIONS: Self-perceived health differences in the Russian Federation has changed over time. Such differences in changes are attributable to both changes in the distribution of the determinants of health as well as changes in the association between the determinants of health with the self-perceived health status. Though this study identifies the determinants of health inequalities for the Russians, the future research is to examine the in-country distribution of these determinants that produce health differences within the Russian Federation. PMID- 26888647 TI - Bringing Nature to Schools to Promote Children's Physical Activity. AB - Physical activity (PA) is essential for human health and wellbeing across all age, socioeconomic, and ethnic groups. Engagement with the natural world is a new defining criterion for enhancing the benefits of PA, particularly for children and young people. Interacting with nature benefits children's social and emotional wellbeing, develops resilience, and reduces the risk of obesity and type 2 diabetes mellitus across all population groups. Governments around the world are now recognizing the importance of children spending more active time outdoors. However, children's outdoor activities, free play, and nature-related exploration are often structured and supervised by adults due to safety concerns and risks. In this context, schools become more accessible and safe options for children to engage in PA outdoors with the presence of nature features. Research on school designs involving young children has revealed that children prefer nature-related features in school environments. Affordances in nature may increase children's interest in physically active behaviors. Given that present school campuses are designed for operational efficiency and economic reasons, there is a need to re-design schools responding to the positive role of nature on human health. If schools were re-designed to incorporate diverse natural features, children's PA and consequent health and wellbeing would likely improve markedly. PMID- 26888651 TI - Facial surgeons call for review of two week cancer referral system. PMID- 26888650 TI - Variations in prebiotic oligosaccharide fermentation by intestinal lactic acid bacteria. AB - Prebiotic oligosaccharides confer health benefits on the host by modulating the gut microbiota. Intestinal lactic acid bacteria (LAB) are potential targets of prebiotics; however, the metabolism of oligosaccharides by LAB has not been fully characterized. Here, we studied the metabolism of eight oligosaccharides by 19 strains of intestinal LAB. Among the eight oligosaccharides used, 1-kestose, lactosucrose and galactooligosaccharides (GOSs) led to the greatest increases in the numbers of the strains tested. However, mono- and disaccharides accounted for more than half of the GOSs used, and several strains only metabolized the mono- and di-saccharides in GOSs. End product profiles indicated that the amounts of lactate produced were generally consistent with the bacterial growth recorded. Oligosaccharide profiling revealed the interesting metabolic manner in Lactobacillus paracasei strains, which metabolized all oligosaccharides, but left sucrose when cultured with fructooligosaccharides. The present study clearly indicated that the prebiotic potential of each oligosaccharide differs. PMID- 26888649 TI - Calstabin 2: An important regulator for learning and memory in mice. AB - Calstabin2, also named FK506 binding protein 12.6 (FKBP12.6), is a subunit of ryanodine receptor subtype 2 (RyR2) macromolecular complex, which is an intracellular calcium channel and abundant in the brain. Previous studies identified a role of leaky neuronal RyR2 in posttraumatic stress disorder (PTSD). However, the functional role of Calstabin2 in the cognitive function remains unclear. Herein, we used a mouse model of genetic deletion of Calstabin2 to investigate the function of Calstabin2 in cognitive dysfunction. We found that Calstabin2 knockout (KO) mice showed significantly reduced performance in Morris Water Maze (MWM), long-term memory (LTM) contextual fear testing, and rotarod test when compared to wild type (WT) littermates. Indeed, genetic deletion of Calstabin2 reduced long-term potentiation (LTP) at the hippocampal CA3-CA1 connection, increased membrane excitability, and induced RyR2 leak. Finally, we demonstrated that the increase in cytoplasmic calcium activated Ca(2+) dependent potassium currents and led to neuronal apoptosis in KO hippocampal neurons. Thus, these results suggest that neuronal RyR2 Ca(2+) leak due to Calstabin2 deletion contributes to learning deficiency and memory impairment. PMID- 26888646 TI - What are the Physiological Mechanisms for Post-Exercise Cold Water Immersion in the Recovery from Prolonged Endurance and Intermittent Exercise? AB - Intense training results in numerous physiological perturbations such as muscle damage, hyperthermia, dehydration and glycogen depletion. Insufficient/untimely restoration of these physiological alterations might result in sub-optimal performance during subsequent training sessions, while chronic imbalance between training stress and recovery might lead to overreaching or overtraining syndrome. The use of post-exercise cold water immersion (CWI) is gaining considerable popularity among athletes to minimize fatigue and accelerate post-exercise recovery. CWI, through its primary ability to decrease tissue temperature and blood flow, is purported to facilitate recovery by ameliorating hyperthermia and subsequent alterations to the central nervous system (CNS), reducing cardiovascular strain, removing accumulated muscle metabolic by-products, attenuating exercise-induced muscle damage (EIMD) and improving autonomic nervous system function. The current review aims to provide a comprehensive and detailed examination of the mechanisms underpinning acute and longer term recovery of exercise performance following post-exercise CWI. Understanding the mechanisms will aid practitioners in the application and optimisation of CWI strategies to suit specific recovery needs and consequently improve athletic performance. Much of the literature indicates that the dominant mechanism by which CWI facilitates short term recovery is via ameliorating hyperthermia and consequently CNS mediated fatigue and by reducing cardiovascular strain. In contrast, there is limited evidence to support that CWI might improve acute recovery by facilitating the removal of muscle metabolites. CWI has been shown to augment parasympathetic reactivation following exercise. While CWI-mediated parasympathetic reactivation seems detrimental to high-intensity exercise performance when performed shortly after, it has been shown to be associated with improved longer term physiological recovery and day to day training performances. The efficacy of CWI for attenuating the secondary effects of EIMD seems dependent on the mode of exercise utilised. For instance, CWI application seems to demonstrate limited recovery benefits when EIMD was induced by single-joint eccentrically biased contractions. In contrast, CWI seems more effective in ameliorating effects of EIMD induced by whole body prolonged endurance/intermittent based exercise modalities. PMID- 26888652 TI - Repair of critical size defects using bioactive glass seeded with adipose-derived mesenchymal stem cells. AB - Bioactive glass has been demonstrated as a biocompatible bone substitute. However bone healing process can be prolonged due to late resorption of the material. Adipose derived stem cells (ASC) have osteogenic differentiation potential and hence can be a cell source for bone regeneration. The aim of this study was to test whether combination of bioactive glass with ASCs would enhance bone regeneration. Following creation of critical sized defects on the calvaria of 32 Wistar rats, the animals were randomly divided into four groups: Group C (control): Defects were left untreated; Group G: Defects were covered with autologous bone graft; Group BG: Defects were filled with bioactive glass; Group BG/ASC: Defects were filled with bioactive glass seeded with ASCs. The defect size was significantly greater in Group C compared to all other groups. Bone density was significantly lower in Group C compared to Group G and Group BG/ASC. Bone regeneration score of Group C was significantly lower than other groups. Group BG/ASC demonstrated lamellar bone and havers canal formation. The results of this study demonstrated that bioactive glass implanted with ASC is a biocompatible construct stimulating radiologically and histologically evident bone regeneration similar to autologous bone grafting. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1002-1008, 2017. PMID- 26888653 TI - Peer volunteer perspectives following a complex social cognitive intervention: a qualitative investigation. AB - BACKGROUND: Peer volunteers can be key to delivering effective social cognitive interventions due to increased potential for social modeling. We consulted peer volunteers who had just taken part in an 8-week social and nutritional mealtime intervention with older adults living alone, to seek their evaluation of the intervention. METHODS: Semi-structured focus groups were used with a total of 21 volunteers (17 female) and two facilitators. Thematic analysis was used to interrogate the data. RESULTS: Six themes (16 sub-themes) are discussed. Peer volunteers described the importance of the socializing aspect of the intervention, of pairing considerations and compatibility in peer interventions, of considering the needs of the participant, of benefits to the volunteers, and of the practical considerations of conducting an intervention. Volunteers also discussed considerations for future research and services for older adults living alone. CONCLUSIONS: Volunteers found their involvement in the intervention to be personally beneficial, and revealed some valuable considerations for the researchers to take forward to future research. Results are pertinent to intervention design and could inform future social cognitive and other peer oriented interventions for older adults living alone. PMID- 26888648 TI - Monitoring Athletic Training Status Through Autonomic Heart Rate Regulation: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Autonomic regulation of heart rate (HR) as an indicator of the body's ability to adapt to an exercise stimulus has been evaluated in many studies through HR variability (HRV) and post-exercise HR recovery (HRR). Recently, HR acceleration has also been investigated. OBJECTIVE: The aim of this systematic literature review and meta-analysis was to evaluate the effect of negative adaptations to endurance training (i.e., a period of overreaching leading to attenuated performance) and positive adaptations (i.e., training leading to improved performance) on autonomic HR regulation in endurance-trained athletes. METHODS: We searched Ovid MEDLINE, Embase, CINAHL, SPORTDiscus, PubMed, and Academic Search Premier databases from inception until April 2015. Included articles examined the effects of endurance training leading to increased or decreased exercise performance on four measures of autonomic HR regulation: resting and post-exercise HRV [vagal-related indices of the root-mean-square difference of successive normal R-R intervals (RMSSD), high frequency power (HFP) and the standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) only], and post-exercise HRR and HR acceleration. RESULTS: Of the 5377 records retrieved, 27 studies were included in the systematic review and 24 studies were included in the meta-analysis. Studies inducing increases in performance showed small increases in resting RMSSD [standardised mean difference (SMD) = 0.58; P < 0.001], HFP (SMD = 0.55; P < 0.001) and SD1 (SMD = 0.23; P = 0.16), and moderate increases in post-exercise RMSSD (SMD = 0.60; P < 0.001), HFP (SMD = 0.90; P < 0.04), SD1 (SMD = 1.20; P = 0.04), and post-exercise HRR (SMD = 0.63; P = 0.002). A large increase in HR acceleration (SMD = 1.34) was found in the single study assessing this parameter. Studies inducing decreases in performance showed a small increase in resting RMSSD (SMD = 0.26; P = 0.01), but trivial changes in resting HFP (SMD = 0.04; P = 0.77) and SD1 (SMD = 0.04; P = 0.82). Post-exercise RMSSD (SMD = 0.64; P = 0.04) and HFP (SMD = 0.49; P = 0.18) were increased, as was HRR (SMD = 0.46; P < 0.001), while HR acceleration was decreased (SMD = -0.48; P < 0.001). CONCLUSIONS: Increases in vagal-related indices of resting and post-exercise HRV, post-exercise HRR, and HR acceleration are evident when positive adaptation to training has occurred, allowing for increases in performance. However, increases in post-exercise HRV and HRR also occur in response to overreaching, demonstrating that additional measures of training tolerance may be required to determine whether training-induced changes in these parameters are related to positive or negative adaptations. Resting HRV is largely unaffected by overreaching, although this may be the result of methodological issues that warrant further investigation. HR acceleration appears to decrease in response to overreaching training, and thus may be a potential indicator of training-induced fatigue. PMID- 26888654 TI - Universal pulses: A new concept for calibration-free parallel transmission. AB - PURPOSE: A calibration-free parallel transmission method is investigated to mitigate the radiofrequency (RF) field inhomogeneity problem in brain imaging at 7 Tesla (T). THEORY AND METHODS: Six volunteers were scanned to build a representative database of RF and static field maps at 7T. Small-tip-angle and inversion pulses were designed with joint kT -points trajectory optimization to work robustly on all six subjects. The returned "universal" pulses were then inserted in an MPRAGE sequence implemented on six additional volunteers without further field measurements and pulse optimizations. Similar acquisitions were performed in the circularly polarized mode and with subject-based optimizations for comparison. Performance of the different approaches was evaluated by means of image analysis and computation of the flip angle normalized root mean square errors (NRMSE). RESULTS: For both the excitation and inversion, the universal pulses (NRMSE~11%) outperformed the circularly polarized (NRMSE~28%) and RF shim modes (NRMSE~20%) across all volunteers and returned slightly worse results than for subject-based optimized pulses (NRMSE~7%). CONCLUSION: RF pulses can be designed to robustly mitigate the RF field inhomogeneity problem over a population class. This appears as a first step toward another plug and play parallel transmission solution where the pulse design can be done offline and without measuring subject-specific field maps. Magn Reson Med 77:635-643, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26888655 TI - A Review of Simulators with Haptic Devices for Medical Training. AB - Medical procedures often involve the use of the tactile sense to manipulate organs or tissues by using special tools. Doctors require extensive preparation in order to perform them successfully; for example, research shows that a minimum of 750 operations are needed to acquire sufficient experience to perform medical procedures correctly. Haptic devices have become an important training alternative and they have been considered to improve medical training because they let users interact with virtual environments by adding the sense of touch to the simulation. Previous articles in the field state that haptic devices enhance the learning of surgeons compared to current training environments used in medical schools (corpses, animals, or synthetic skin and organs). Consequently, virtual environments use haptic devices to improve realism. The goal of this paper is to provide a state of the art review of recent medical simulators that use haptic devices. In particular we focus on stitching, palpation, dental procedures, endoscopy, laparoscopy, and orthopaedics. These simulators are reviewed and compared from the viewpoint of used technology, the number of degrees of freedom, degrees of force feedback, perceived realism, immersion, and feedback provided to the user. In the conclusion, several observations per area and suggestions for future work are provided. PMID- 26888656 TI - Fetal alcohol spectrum disorders are clearly brain-based. PMID- 26888657 TI - Does knowledge of fetal outcome influence the interpretation of intrapartum cardiotocography and subsequent clinical management? A multicentre European study. AB - OBJECTIVE: To investigate whether knowledge of fetal outcome influences retrospective interpretation of cardiotocographic tracings and subsequent management recommendations. DESIGN: Prospective online study. SETTING: Seven university hospitals in five European countries. POPULATION: Forty-two intrapartum tracings from women with singleton pregnancies and uneventful antepartum courses. METHODS: Using an online questionnaire, 123 healthcare professionals interpreted 42 tracings without any knowledge of fetal outcome and provided management recommendations according to the National Institute of Clinical Excellence guidelines (intrapartum care). Two months later, 93 of the 123 participants re-interpreted the same re-ordered tracings, this time with information on the newborn's umbilical artery pH. OUTCOME MEASURES: Comparison of the evaluation of tracing features, overall tracing classification, and management recommendations between the initial analysis and re-interpretation. RESULTS: In newborns with umbilical artery pH <= 7.05, knowledge of the pH value led to significant changes in the evaluation of all basic tracing features. In this group, classification of tracings as 'normal' decreased 76% (8.8-2.1%, P < 0.001), whereas classification as 'pathologic' increased 51% (44.7-67.5%, P < 0.001). In newborns with pH 7.06-7.19, classification of tracings as 'normal' decreased 36% (22.4-14.4%, P < 0.001), and in those with pH >= 7.20, classification of tracings as 'pathologic' decreased 40% (23.4-14.1%, P < 0.001). In the group of newborns with umbilical artery pH <= 7.05, the recommendations 'no attention needed' decreased 75% (10.2-2.6%, P < 0.001), and the number of recommendations 'rapid reversal of hypoxic cause or immediate delivery' increased 70.3% (42.1-71.7%, P < 0.001). CONCLUSIONS: When provided with information on adverse fetal outcome, healthcare professionals provide a more pessimistic evaluation of basic tracing features, overall classification, and clinical management recommendations. TWEETABLE ABSTRACT: Knowledge of adverse fetal outcome leads to more pessimistic CTG evaluation and management recommendations. PMID- 26888658 TI - Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands. AB - OBJECTIVES: Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. METHODS: Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. RESULTS: 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). CONCLUSIONS: This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. PMID- 26888659 TI - Missed opportunities for HIV testing of patients diagnosed with an indicator condition in primary care in Catalonia, Spain. AB - OBJECTIVE: To estimate the prevalence of HIV testing among patients diagnosed with an indicator condition (IC) for HIV, seen in primary care (PC) in Catalonia, and to estimate the prevalence of HIV infection among those patients. DESIGN: Cross-sectional and population-based study in patients aged between 16 and 65 diagnosed with an IC within PC in Catalonia. METHODS: Data used in this study were extracted from a large population-based public health database in Spain, the Information System for the Development of Research in Primary Care (SIDIAP). All participants registered in SIDIAP from 1 January 2010 to 31 August 2012 and with a diagnosis of an IC were screened to identify those with an HIV test within the following 4 months. RESULTS: 99 426 patients were diagnosed with an IC during the study period. In these patients, there were 102 647 episodes in which at least one IC was diagnosed. An HIV test was performed within 4 months in only 18 515 of the episodes in which an IC was diagnosed (18.5%). The prevalence of HIV infection was 1.46%. Women (OR 1.35, 95% CI 1.30 to 1.39), people aged 50 or over (OR 2.85, 95% CI 2.69 to 3.00) and patients having a single IC (OR 3.59. 95% CI 3.20 to 4.03) had the greatest odds of not having an HIV test. CONCLUSIONS: The study highlights the persistence of missed opportunities for HIV testing within PC in Catalonia. Urgent engagement with PC professionals is required in order to increase HIV testing and prevent late HIV diagnoses. PMID- 26888660 TI - Trends in gonorrhoea positivity by nucleic acid amplification test versus culture among Australian heterosexual men with a low prevalence of gonorrhoea, 2007-2014. AB - BACKGROUND: Testing for gonorrhoea with nucleic acid amplification tests (NAATs) is not recommended in low-prevalence populations as it results in high numbers of false positive results. The aim of this study was to examine temporal trends of gonorrhoea positivity by NAAT and culture in heterosexual men in Victoria, Australia following recent increases in gonorrhoea notifications. METHODS: Three data sources between 2007 and 2014 were used in this study: notification data from the Victorian Department of Health, Medicare testing numbers of single chlamydia and dual NAATs performed, and electronic records on heterosexual men attending Melbourne Sexual Health Centre (MSHC). RESULTS: Notifications of gonorrhoea by NAAT (with/without culture) in heterosexual men in Victoria rose threefold from 74 in 2007 to 238 in 2014, while the number of dual NAATs ordered over the same period underwent a fivefold increase from 14 061 to 71 860. The overall proportion of NAATs that were positive for gonorrhoea in Victoria was low and fell from 0.53% in 2007 to 0.33% in 2014 (Ptrend=0.002). Of the 28014 new heterosexual men attending MSHC, the gonorrhoea positivity by culture was 0.9%, and chlamydia positivity by NAAT was 8.5%. The positivity of both infections did not change over time. CONCLUSIONS: These data suggest that gonorrhoea prevalence in heterosexual men is low and stable, despite annual increases in notifications. Guidelines in most countries recommend restricting testing to groups or populations with prevalence over 1%, symptomatic individuals or those at increased epidemiological risk. These data indicate gonorrhoea testing should not automatically accompany chlamydia screening in low-risk heterosexual men. PMID- 26888661 TI - Analyzing clinical trial outcomes based on incomplete daily diary reports. AB - A case study is presented assessing the impact of missing data on the analysis of daily diary data from a study evaluating the effect of a drug for the treatment of insomnia. The primary analysis averaged daily diary values for each patient into a weekly variable. Following the commonly used approach, missing daily values within a week were ignored provided there was a minimum number of diary reports (i.e., at least 4). A longitudinal model was then fit with treatment, time, and patient-specific effects. A treatment effect at a pre-specified landmark time was obtained from the model. Weekly values following dropout were regarded as missing, but intermittent daily missing values were obscured. Graphical summaries and tables are presented to characterize the complex missing data patterns. We use multiple imputation for daily diary data to create completed data sets so that exactly 7 daily diary values contribute to each weekly patient average. Standard analysis methods are then applied for landmark analysis of the completed data sets, and the resulting estimates are combined using the standard multiple imputation approach. The observed data are subject to digit heaping and patterned responses (e.g., identical values for several consecutive days), which makes accurate modeling of the response data difficult. Sensitivity analyses under different modeling assumptions for the data were performed, along with pattern mixture models assessing the sensitivity to the missing at random assumption. The emphasis is on graphical displays and computational methods that can be implemented with general-purpose software. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888662 TI - Interstitial lung abnormalities are linked to increased risk of death. PMID- 26888663 TI - A web-oriented software for the optimization of pooled experiments in NGS for detection of rare mutations. AB - BACKGROUND: The cost per patient of next generation sequencing for detection of rare mutations may be significantly reduced using pooled experiments. Recently, some techniques have been proposed for the planning of pooled experiments and for the optimal allocation of patients into pools. However, the lack of a user friendly resource for planning the design of pooled experiments forces the scientists to do frequent, complex and long computations. RESULTS: OPENDoRM is a powerful collection of novel mathematical algorithms usable via an intuitive graphical user interface. It enables researchers to speed up the planning of their routine experiments, as well as, to support scientists without specific bioinformatics expertises. Users can automatically carry out analysis in terms of costs associated with the optimal allocation of patients in pools. They are also able to choose between three distinct pooling mathematical methods, each of which also suggests the optimal configuration for the submitted experiment. Importantly, in order to keep track of the performed experiments, users can save and export the results of their experiments in standard tabular and charts contents. CONCLUSION: OPENDoRM is a freely available web-oriented application for the planning of pooled NGS experiments, available at: http://www labgtp.na.icar.cnr.it/OPENDoRM. Its easy and intuitive graphical user interface enables researchers to plan theirs experiments using novel algorithms, and to interactively visualize the results. PMID- 26888664 TI - A strain or electric field induced direct bandgap in ultrathin silicon film and its application in photovoltaics or photocatalysis. AB - The indirect bandgap character of silicon greatly limits its applications in electronic or optoelectronic devices, and direct bandgaps are highly desirable in all silicon allotropes. The successful synthesis of ultrathin or even monolayer silicon films experimentally has opened new opportunities to further modulate the electronic structure of silicon through external modulation. In this work, strain or electric field effects on the electronic structure of ultrathin silicon film (USF) are systematically explored. The results demonstrate that all USFs are indirect band-gap semiconductors; interestingly, tensile strain or electric field efficiently tunes the USFs into direct band gap semiconductors. The indirect to direct band gap transition in the USFs not only extends their light adsorption spectra into the visible light region but also greatly enhances the adsorption intensity. Because of this, strained USFs have great potential to be used as a high-performance photovoltaic material. Furthermore, the high stability, moderate band-gap and proper band edge positions demonstrate that monolayer and bilayer USFs can also be used as photocatalysts for water splitting. PMID- 26888667 TI - Patterns and Rates of Supplementary Venous Drainage to the Internal Jugular Veins. AB - BACKGROUND AND PURPOSE: Several studies have found supplemental venous drainage channels in addition to bilateral internal jugular veins for cerebral venous efflux. We performed this study to characterize the supplemental venous outflow patterns in a consecutive series of patients undergoing detailed cerebral angiography with venous phase imaging. METHODS: The venographic phase of the arteriogram was reviewed to identify and classify supplemental cerebral venous drainage into anterior (cavernous venous sinus draining into pterygoid plexus and retromandibular vein) and posterior drainage pattern. The posterior drainage pattern was further divided into plexiform pattern (with sigmoid venous sinus draining into the paravertebral venous plexus), and solitary vein pattern (dominant single draining deep cervical vein) drainage. The posterior plexiform pattern was further divided into 2 groups: posterior plexiform with or without prominent solitary vein. RESULTS: Supplemental venous drainage was seen ipsilateral to internal jugular vein in 76 (43.7%) of 174 venous drainages (87 patients) analyzed. The patterns were anterior (n = 23, 13.2%), posterior plexiform without prominent solitary vein (n = 40, 23%), posterior plexiform with prominent solitary vein (n = 62, 35.6%), and posterior solitary vein alone (n = 3, 1.7%); occipital emissary veins and/or transosseous veins were seen in 1 supplemental venous drainage. Concurrent ipsilateral anterior and posterior supplemental drainage was seen in 6 of 174 venous drainages analyzed. CONCLUSIONS: We provide an assessment of patterns and rates of supplementary venous drainage to internal jugular veins to improve our understanding of anatomical and physiological aspects of cerebral venous drainage. PMID- 26888666 TI - Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self-renewal of MSCs in culture. HMGA2 is a DNA-binding protein that regulates self-renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let-7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF-2, a growth factor commonly used to promote self-renewal in MSCs, rapidly induces HMGA2 expression in a time- and concentration-dependent manner. The signaling pathway involves FGF-2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let-7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over-expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF-2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF-2, and is involved in both proliferation and adipogenesis of MSCs. J. Cell. Biochem. 117: 2128-2137, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26888668 TI - Direct water-phase synthesis of lead sulfide quantum dots encapsulated by beta lactoglobulin for in vivo second near infrared window imaging with reduced toxicity. AB - Compared to conventional fluorescence imaging in the visible (400-700 nm) and NIR I regions (700-900 nm), optical fluorescence imaging in the second near infrared window (NIR-II, 1000-1400 nm) offers reduced photon scattering, deeper tissue penetration and lower auto-fluorescence. Despite excellent imaging capabilities, current NIR-II probes have not yet reached their full potential due to weak quantum yield, low water solubility and suboptimal biocompatibility. To address these problems, we report herein a new NIR-II fluorescent PbS quantum dots (QDs) that are fabricated in water using beta-lactoglobulin (LG) as a biological template. The LG-PbS QDs exhibit satisfactory dispersibility, relatively high quantum yield and favorable biocompatibility, and therefore are suitable for high resolution in vivo imaging applications. PMID- 26888665 TI - Relationship between total phenolic contents and biological properties of propolis from 20 different regions in South Korea. AB - BACKGROUND: Propolis (or bee glue), collected from botanical sources by honey bee, has been used as a popular natural remedies in folk medicine throughout the world. This study was conducted to assess growth inhibitory effects of ethanol extracts of propolis (EEPs) from 20 different regions in South Korea on human intestinal bacteria as well as their human beta-amyloid precursor cleavage enzyme (BACE-1), acetylcholinesterase (AChE) inhibitory, antioxidant, antiproliferative, and anti-human rhinovirus activities. METHODS: The Bonferroni multiple-comparison method was used to test for significant differences in total polyphenol and flavonoid contents among EEP samples using SAS 9.13 program. Correlation coefficient (r) analysis of the biological activities of EEP samples was determined using their 50 % inhibition concentration or minimal inhibitory concentration values and their polyphenol or flavonoid contents in 20 native Korean EEP samples. RESULTS: The amounts of total polyphenol and flavonoids in the Korean EEP samples ranged from 49 to 239 mg gallic acid equivalent (GAE)/g EEP (Brazilian, Chinese, and Australian samples, 127-142 mg GAE/g EEP) and from 21 to 50 mg quercetin equivalent (QE)/g EEP (Brazilian, Chinese, and Australian samples, 33-53 mg QE/g EEP), respectively. Correlation coefficient analysis showed that total polyphenol contents may be negatively correlated with 2,2 diphenyl-1-picrylhydrazyl free radical scavenging activity (r = -0.872) and total flavonoid content has no correlation with the activity (r = 0.071). No direct correlation between BACE-1 inhibition, AChE inhibition, or antiproliferative activity and total polyphenol or total flavonoid content in Korean EEP samples was found. Gram-positive and Gram-negative bacteria were observed to have different degrees of antimicrobial susceptibility to the EEP samples examined, although ciprofloxacin susceptibility among the bacterial groups did not differ greatly. CONCLUSIONS: Further studies will warrant possible applications of propolis as potential therapeutic BACE-1 blocker, antioxidant, antiproliferative agent, and antimicrobial agent. PMID- 26888670 TI - Photodistributed telangiectasia following use of escitalopram. PMID- 26888671 TI - Unusual presentation of ingested wire bristle extruded through abdominal wall. PMID- 26888669 TI - Mark4 promotes oxidative stress and inflammation via binding to PPARgamma and activating NF-kappaB pathway in mice adipocytes. AB - MAP/Microtubule affinity-regulating kinase 4 (Mark4) plays an important role in the regulation of microtubule organization, adipogenesis and apoptosis. However, the role of Mark4 plays in oxidative stress and inflammation are poorly understood. In this study, we found Mark4 was induced by high fat diet (HFD) while PPARgamma was elevated significantly in mice adipocytes. Further analyses revealed Mark4 impaired mitochondrial oxidative respiration and increased reactive oxygen species (ROS) production. At same time, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were greatly reduced. By treating cells with H2O2 and vitamin E (VE), Mark4 accentuated oxidative stress along with increased mRNA level of inflammatory factor interleukin-6 (IL-6) and decreased leptin mRNA. Furthermore, we found PPARgamma bind to Mark4 promoter region and inhibited Mark4 expression. We showed PPARgamma interacted with Mark4 and inhibited the stimulating effect of Mark4 on oxidative stress and inflammation. Finally, we demonstrated that the IKKalpha/NF kappaB signal pathway was involved in Mark4 induced oxidative stress and inflammation, while PTDC, a special inhibitor of NF-kappaB signal pathway, reduced oxidative stress and inflammation. Thus, our study indicated that Mark4 was a potential drug target for treating metabolic diseases. PMID- 26888672 TI - Mental Health Has a Stronger Association with Patient-Reported Shoulder Pain and Function Than Tear Size in Patients with Full-Thickness Rotator Cuff Tears. AB - BACKGROUND: Patient-reported outcome measures have increasingly accompanied objective examination findings in the evaluation of orthopaedic interventions. Our objective was to determine whether a validated measure of mental health (Short Form-36 Mental Component Summary [SF-36 MCS]) or measures of tear severity on magnetic resonance imaging were more strongly associated with self-assessed shoulder pain and function in patients with symptomatic full-thickness rotator cuff tears. METHODS: One hundred and sixty-nine patients with full-thickness rotator cuff tears were prospectively enrolled. Patients completed the Short Form 36, visual analog scales for shoulder pain and function, the Simple Shoulder Test (SST), and the American Shoulder and Elbow Surgeons (ASES) instrument at the time of diagnosis. Shoulder magnetic resonance imaging examinations were reviewed to document the number of tendons involved, tear size, tendon retraction, and tear surface area. Age, sex, body mass index, number of medical comorbidities, smoking status, and Workers' Compensation status were recorded. Bivariate correlations and multivariate regression models were calculated to identify associations with baseline shoulder scores. RESULTS: The SF-36 MCS had the strongest correlation with the visual analog scale for shoulder pain (Pearson correlation coefficient, 0.48; p < 0.001), the visual analog scale for shoulder function (Pearson correlation coefficient, -0.33; p < 0.001), the SST (Pearson correlation coefficient, 0.37; p < 0.001), and the ASES score (Pearson correlation coefficient, 0.51; p < 0.001). Tear severity only correlated with the visual analog scale for shoulder function; the Pearson correlation coefficient was 0.19 for tear size (p = 0.018), 0.18 for tendon retraction (p = 0.025), 0.18 for tear area (p = 0.022), and 0.20 for the number of tendons involved (p = 0.011). Tear severity did not correlate with other scores in bivariate correlations (all p > 0.05). In all multivariate models, the SF-36 MCS had the strongest association with the visual analog scale for shoulder pain, the visual analog scale for shoulder function, the SST, and the ASES score (all p < 0.001). CONCLUSIONS: Patient mental health may play an influential role in patient-reported pain and function in patients with full-thickness rotator cuff tears. Further studies are needed to determine its effect on the outcome of the treatment of rotator cuff disease. PMID- 26888673 TI - Comparison of Whole-Blood Metal Ion Levels Among Four Types of Large-Head, Metal on-Metal Total Hip Arthroplasty Implants: A Concise Follow-up, at Five Years, of a Previous Report. AB - Few studies of total hip arthroplasty (THA) implants with a large-diameter femoral head and metal-on-metal design have directly compared the progression of metal ion levels over time and the relationship to complications. As we previously reported, 144 patients received one of four types of large-diameter head, metal-on-metal THA designs (Durom, Birmingham, ASR XL, or Magnum implants). Cobalt, chromium, and titanium ion levels were measured over five years. We compared ion levels and clinical results over time. The Durom group showed the highest levels of cobalt (p <= 0.002) and titanium ions (p <= 0.03). Both the Durom and Birmingham groups demonstrated significant ongoing cobalt increases up to five years. Eight patients (seven with a Durom implant and one with a Birmingham implant) developed adverse local tissue reaction. Six Durom implants and one Birmingham implant required revision, with one pseudotumor under surveillance at the time of the most recent follow-up. We found that ion generation and related complications varied among designs. More concerning was that, for some designs, ion levels continued to increase. Coupling a cobalt chromium adapter sleeve to an unmodified titanium femoral trunnion along with a large metal-on-metal bearing may explain the poor performances of two of the designs in the current study. PMID- 26888674 TI - Intramedullary Nailing Compared with Spica Casts for Isolated Femoral Fractures in Four and Five-Year-Old Children. AB - BACKGROUND: Flexible intramedullary nailing (IMN) is a valuable tool in the treatment of femoral fractures in school-age children, whereas spica cast immobilization has been the standard of care for younger children. We compared these treatment modalities in a group of preschool-age children (four to five years of age). METHODS: A retrospective cohort of consecutive patients, four to five years of age, with an isolated, complete femoral shaft or subtrochanteric fracture treated with intramedullary nailing or early spica cast immobilization and followed until fracture-healing were identified from two centers. Radiographic and clinical outcomes were compared between the groups. Statistical methods included chi-square and Fisher exact tests for categorical variables and the Mann-Whitney test for continuous variables. RESULTS: Two hundred and sixty two patients followed for a mean of thirty-two weeks were identified. One hundred and four patients underwent IMN and 158 patients were treated with immediate spica cast immobilization at the surgeon's discretion. The patients who underwent IMN were older than those who underwent spica cast immobilization (mean, 5.2 versus 4.7 years; p < 0.001), were heavier (mean, 21.5 versus 18.0 kg; p < 0.001), and were more likely to have a higher-energy mechanism of injury (p = 0.025). At the time of final follow-up, there was no difference between groups with regard to the percentages of patients who had acceptable coronal angulation (<=15 degrees ), sagittal angulation (<=20 degrees ), and early fracture shortening (<=20 mm) (96.2% in the spica group versus 99.0% in the IMN group; p = 0.09). While there was no significant difference in the percentages who had an unplanned return to the operating room (3.8% in the IMN group versus 4.4% in the spica group; p > 0.99), the patients in the IMN group had more clinic visits (mean, 5.8 versus 4.0; p < 0.001) and longer follow-up (mean, forty-four versus twenty-five weeks; p < 0.001) than the patients in the spica group and a higher percentage of them underwent repeat procedures (89.4% versus 5.1%; p < 0.001), primarily for elective implant removal. CONCLUSIONS: Preschool-age children (four to five years old) with an isolated femoral fracture have similar clinical and radiographic outcomes regardless of whether they are treated with immediate spica cast immobilization or IMN. PMID- 26888675 TI - Motion Predicts Clinical Callus Formation: Construct-Specific Finite Element Analysis of Supracondylar Femoral Fractures. AB - BACKGROUND: Mechanotransduction is theorized to influence fracture-healing, but optimal fracture-site motion is poorly defined. We hypothesized that three dimensional (3-D) fracture-site motion as estimated by finite element (FE) analysis would influence callus formation for a clinical series of supracondylar femoral fractures treated with locking-plate fixation. METHODS: Construct specific FE modeling simulated 3-D fracture-site motion for sixty-six supracondylar femoral fractures (OTA/AO classification of 33A or 33C) treated at a single institution. Construct stiffness and directional motion through the fracture were investigated to assess the validity of construct stiffness as a surrogate measure of 3-D motion at the fracture site. Callus formation was assessed radiographically for all patients at six, twelve, and twenty-four weeks postoperatively. Univariate and multivariate linear regression analyses examined the effects of longitudinal motion, shear (transverse motion), open fracture, smoking, and diabetes on callus formation. Construct types were compared to determine whether their 3-D motion profile was associated with callus formation. RESULTS: Shear disproportionately increased relative to longitudinal motion with increasing bridge span, which was not predicted by our assessment of construct stiffness alone. Callus formation was not associated with open fracture, smoking, or diabetes at six, twelve, or twenty-four weeks. However, callus formation was associated with 3-D fracture-site motion at twelve and twenty-four weeks. Longitudinal motion promoted callus formation at twelve and twenty-four weeks (p = 0.017 for both). Shear inhibited callus formation at twelve and twenty-four weeks (p = 0.017 and p = 0.022, respectively). Titanium constructs with a short bridge span demonstrated greater longitudinal motion with less shear than did the other constructs, and this was associated with greater callus formation (p < 0.001). CONCLUSIONS: In this study of supracondylar femoral fractures treated with locking-plate fixation, longitudinal motion promoted callus formation, while shear inhibited callus formation. Construct stiffness was found to be a poor surrogate of fracture-site motion. Future implant design and operative fixation strategies should seek to optimize 3-D fracture-site motion rather than rely on surrogate measures such as axial stiffness. PMID- 26888676 TI - Particle-Induced Osteolysis Is Mediated by TIRAP/Mal in Vitro and in Vivo: Dependence on Adherent Pathogen-Associated Molecular Patterns. AB - BACKGROUND: Proinflammatory signaling by toll-like receptors (TLRs) likely contributes to biologic responses to wear particles causing aseptic loosening. We recently reported associations with aseptic loosening in patients with polymorphisms in the locus encoding an adapter protein specific for TLR-2 and TLR 4 known as toll/interleukin-1 receptor domain-containing adapter protein/MyD88 adapter-like (TIRAP/Mal). To directly examine the contribution of TIRAP/Mal, we tested the hypothesis that TIRAP/Mal deficiency reduces the activity of wear particles. Signaling by TLR-2 and TLR-4 through TIRAP/Mal can be activated by bacterial pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide or endogenous alarmins. To distinguish between those possibilities, we tested the hypothesis that the effects of TIRAP/Mal depend on the adherence of bacterial PAMPs to the particles. METHODS: In vitro mRNA levels and secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6 were measured after incubating wild-type and TIRAP/Mal(-/-) macrophages in the presence or absence of titanium particles with adherent bacterial debris, so called endotoxin-free particles, or particles with adherent lipopolysaccharide. In vivo osteolysis was measured after implanting titanium particles on the calvaria of wild-type and TIRAP/Mal(-/-) mice. RESULTS: TIRAP/Mal deficiency significantly inhibited the activity of titanium particles with adherent bacterial debris to stimulate in vivo osteolysis and in vitro cytokine mRNAs and secretion. Those effects are dependent on adherent PAMPs because removal of >99% of the adherent bacterial debris from the particles significantly reduced their activity and the remaining activity was not dependent on TIRAP/Mal. Moreover, adherence of highly purified lipopolysaccharide to the endotoxin-free particles reconstituted the activity and the dependence on TIRAP/Mal. CONCLUSIONS: TIRAP/Mal deficiency reduces inflammatory responses and osteolysis induced by particles with adherent PAMPs. CLINICAL RELEVANCE: Our results, coupled with the genetic associations between aseptic loosening and polymorphisms within the TIRAP/Mal locus, support TLR signaling through TIRAP/Mal as one of the factors that enhances the activity of wear particles and further support the hypothesis that bacterial PAMPs likely contribute to aseptic loosening in a subset of patients. PMID- 26888677 TI - Does Surgical Correction of Right Thoracic Scoliosis in Syringomyelia Produce Outcomes Similar to Those in Adolescent Idiopathic Scoliosis? AB - BACKGROUND: Practice guidelines for deformity correction in patients with syringomyelia-associated scoliosis (SMS) remain ill defined. Although surgeons experienced in treating adolescent idiopathic scoliosis (AIS) are commonly called on to treat SMS, no study has directly compared the results of surgical treatment between patients with SMS and those with AIS. The present study was performed to compare the radiographic and clinical outcomes of posterior spinal fusion between patients with right-thoracic SMS and those with right-thoracic AIS. METHODS: Sixty-nine adolescents with SMS were matched with patients with AIS for sex, age, and curve magnitude. Patients were evaluated before surgery, immediately after surgery, and at the latest follow-up examination for changes in curve correction, global coronal balance, and scores on the Scoliosis Research Society (SRS)-22 questionnaire. RESULTS: The preoperative primary curve magnitude was similar between the two groups, but a trend toward less flexibility was observed in the SMS group. The amount of correction of the thoracic Cobb angles obtained surgically (68% compared with 71%) and the ratio of percent correction to flexibility (1.80 compared with 1.76) were similar in the SMS and AIS groups. At the latest evaluation, eight patients with SMS and five with AIS had lost >10 degrees of thoracic spine correction (p = 0.382). The postoperative coronal decompensation averaged 13% and 6%, respectively, in the SMS and AIS groups (p = 0.243). No intergroup differences were noted with respect to the sagittal vertical axis or proximal junctional change, with preservation of global sagittal balance in both groups during follow-up. There were no neurologic or other major complications related to surgery in either group. CONCLUSIONS: Despite the differences in preoperative status, adolescents with idiopathic right thoracic scoliosis and those with syringomyelia-associated right thoracic scoliosis had comparable clinical and radiographic outcomes of pedicle-screw-based posterior spinal fusion, without neurologic complications. PMID- 26888678 TI - Local Treatment with Adjuvant Therapy for Central Atypical Cartilaginous Tumors in the Long Bones: Analysis of Outcome and Complications in One Hundred and Eight Patients with a Minimum Follow-up of Two Years. AB - BACKGROUND: A central atypical cartilaginous tumor (ACT)--formerly known as chondrosarcoma grade 1 (CS1)--is a tumor of intermediate-type malignancy, often treated with surgery. The extent of surgery remains controversial, as some advocate resection and others favor local treatment by curettage. Because of the low prevalence of ACT/CS1, the available data are limited and generally not uniform. The purpose of this study was to present the outcome for a large cohort of patients with ACT/CS1 in the long bones who were treated with curettage and adjuvant phenolization and followed for a minimum of two years according to national guidelines. METHODS: A retrospective study was designed to analyze data from 108 patients treated for central ACT/CS1 in the long bones between 2006 and 2012. All patients were treated with curettage and adjuvant phenolization, and defects were filled with polymethylmethacrylate, bone graft, or bone substitutes. The primary end point was local recurrence or residual tumor. Secondary end points included the type and rate of complications and reoperations. RESULTS: All patients were free from local recurrence at a mean follow-up of 48.7 months (range, 24.3 to 97.5 months). Residual tumor was suspected in five patients, leading to a 95.4% disease-free survival rate. A fracture occurred in eleven patients (10.2%). Other complications were osseous penetration during the surgery (two patients), wound infection (one patient), arthrofibrosis (one patient), and skin necrosis (one patient). Tumor volume was related neither to the risk of fracture nor to the occurrence of residual tumor. CONCLUSIONS: In our experience, curettage of ACT/CS1 in the long bones with adjuvant phenolization is safe, even with large tumors of up to 100 cm(3). Most worrisome is the risk of fracture, which occurred in 10.2% of our patients. Considering the relatively mild behavior of ACT/CS1, less aggressive treatment, by observation or by minimally invasive surgery, could be the next step that should be evaluated prospectively. PMID- 26888679 TI - Surgical Repair Did Not Improve Functional Outcomes More Than Conservative Treatment for Degenerative Rotator Cuff Tears. PMID- 26888680 TI - Platelet-Rich Plasma Injections Were Not Better Than Hyaluronic Acid Injections for Knee Joint Degeneration. PMID- 26888681 TI - Low-Molecular-Weight Heparin Did Not Differ from Placebo in Preventing Clinically Important Deep Venous Thrombosis After Surgical Repair of Leg Fracture. PMID- 26888682 TI - What's New in Pediatric Orthopaedics. PMID- 26888683 TI - Orthopaedic Patient Information on the World Wide Web: An Essential Review. AB - BACKGROUND: Patients increasingly use the Internet to research health-related issues. Internet content, unlike other forms of media, is not regulated. Although information accessed online can impact patients' opinions and expectations, there is limited information about the quality or readability of online orthopaedic information. METHODS: PubMed, MEDLINE, and Google Scholar were searched using anatomic descriptors and three title keywords ("Internet," "web," and "online"). Articles examining online orthopaedic information from January 1, 2000, until April 1, 2015, were recorded. Articles were assessed for the number of reviewers evaluating the online material, whether the article examined for a link between authorship and quality, and the use of recognized quality and readability assessment tools. To facilitate a contemporary discussion, only publications since January 1, 2010, were considered for analysis. RESULTS: A total of thirty eight peer-reviewed articles published since 2010 examining the quality and/or readability of online orthopaedic information were reviewed. For information quality, there was marked variation in the quality assessment methods utilized, the number of reviewers, and the manner of reporting. To date, the majority of examined information is of poor quality. Studies examining readability have focused on pages produced by professional orthopaedic societies. CONCLUSIONS: The quality and readability of online orthopaedic information are generally poor. CLINICAL RELEVANCE: For modern practices to adapt to the Internet and to prevent misinformation, the orthopaedic community should develop high-quality, readable online patient information. PMID- 26888684 TI - Once Again, the Status of the Rotator Cuff Does Not Correlate with Patient Symptoms: Commentary on an article by James D. Wylie, MD, MHS, et al.: "Mental Health Has a Stronger Association with Patient-Reported Shoulder Pain and Function Than Tear Size in Patients with Full-Thickness Rotator Cuff Tears". PMID- 26888685 TI - Is There a "Best" Road to Rome? Commentary on an article by Brandon A. Ramo, MD, et al.: "Intramedullary Nailing Compared with Spica Casts for Isolated Femoral Fractures in Four and Five-Year-Old Children". PMID- 26888686 TI - Idiopathic Versus Syrinx-Related Scoliosis: How Different Are They? Commentary on an article by Shifu Sha, PhD, et al.: "Does Surgical Correction of Right Thoracic Scoliosis in Syringomyelia Produce Outcomes Similar to Those in Adolescent Idiopathic Scoliosis?". PMID- 26888687 TI - Erratum. PMID- 26888688 TI - Reply to "Nonmotor symptoms in subjects without evidence of dopaminergic deficit" authors: "Swallow DMA, Grosset KA, Grosset DG". PMID- 26888689 TI - Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms. AB - The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26888690 TI - Synthesis and characterization of vertically standing MoS2 nanosheets. AB - Molybdenum disulfide (MoS2) has been attracting much attentions due to its excellent electrical and optical properties. We report here the synthesis of large-scale and uniform MoS2 nanosheets with vertically standing morphology using chemical vapor deposition method. TEM observations clearly reveal the growth mechanism of these vertical structures. It is suggested that the vertical structures are caused by the compression and extrusion between MoS2 islands. More importantly, the vertical morphology of two dimensional (2D) materials hold many promising potential applications. We demonstrate here the as-synthesized vertically standing MoS2 nanosheets could be used for hydrogen evolution reaction, where the exchange current density is about 70 times of bulk MoS2. The field emission performance of vertically standing MoS2 were also improved due to the abundantly exposed edges. PMID- 26888691 TI - Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting. AB - BACKGROUND: Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). MATERIALS AND METHODS: Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. RESULTS: A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). CONCLUSION: This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. PMID- 26888692 TI - Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report. AB - OBJECTIVE: Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer. METHODS: We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment. RESULTS: A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment. CONCLUSION: The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies. PMID- 26888693 TI - Awareness, Understanding, and Adoption of Precision Medicine to Deliver Personalized Treatment for Patients With Cancer: A Multinational Survey Comparison of Physicians and Patients. AB - BACKGROUND: Two separate multinational surveys of oncologists and patients with cancer were conducted to assess the awareness and use of biomarkers in clinical practice. These data explore the self-reported and physician-assessed levels of patient cancer literacy and factors affecting physicians' choice to use biomarkers in treatment decisions. PATIENTS AND METHODS: Interviews were conducted via telephone with patients and online with physicians. Physicians had 3-35 years of experience; were treating more than 15 patients/month; and specialized in breast, lung, or colorectal cancer. Patients had received treatment for breast, lung, or colorectal cancer within the previous 5 years. RESULTS: Interviews with 895 physicians and 811 patients were completed. Most patients and physicians reported that patients understood that a tumor could be tested to determine what treatment would be most effective (78% and 73%, respectively) and that patients would be willing to participate in a personalized treatment plan. Whereas 85% of patients felt that they understood their treatment when it was explained to them, only 23% of doctors felt that their patients were always fully informed. Most physicians (90%) reported using biomarkers; among the 10% not performing biomarker analysis, the most cited obstacles were local availability, speed of obtaining results, and cost. CONCLUSION: These data demonstrate wide global use of biomarker testing but with regional variations reflecting cultural and local practice. Self-reported and physician-assessed cancer literacy, although generally high, highlighted important regional variations and the need to provide patients with additional information. PMID- 26888695 TI - Erratum to: Ability of vaccine strain induced antibodies to neutralize field isolates of caliciviruses from Swedish cats. PMID- 26888696 TI - Non-Invasive Techniques for Detection and Diagnosis of Oral Potentially Malignant Disorders. AB - Oral squamous cell carcinoma (OSCC) is the most common oral and maxillofacial malignancy, and its morbidity and mortality rates are still high in most countries. Oral potentially malignant disorders (PMDs) are used to refer to a heterogeneous group of conditions that are characterized by increased risk for malignant transformation to OSCC. Currently identified oral PMDs include leukoplakia, erythroplakia, palatal lesions associated with reverse smoking, oral lichen planus, oral submucous fibrosis, actinic keratosis, and discoid lupus erythematosus. The early detection and diagnosis of these lesions are important for cancer prevention and disease management. In recent years, there has been a growing and persistent demand for new non-invasive, practical diagnostic techniques that might facilitate the early detection of oral PMDs. The non invasive detection techniques evaluated in this review are divided into four categories: vital staining with a solution that can be used as a mouth rinse or applied onto a suspected area of the mouth, light-based detection systems, optical diagnostic technologies that employ returned optical signals to reflect structural and morphological changes within tissues, and salivary biomarkers. Most of these techniques have shown great potential for screening and monitoring oral PMDs. In this review article, the authors critically assess these non invasive detection techniques for oral PMDs. We also provide a summary of the sensitivity and specificity of each technique in detecting oral PMDs and oral cancer, as well as their advantages, disadvantages, clinical applications, and indications. PMID- 26888694 TI - Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals. AB - Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21-47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21-47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1 hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants. PMID- 26888697 TI - Prevalence of Airflow Limitation Defined by Pre- and Post-Bronchodilator Spirometry in a Community-Based Health Checkup: The Hisayama Study. AB - Spirometry in health checkup may contribute to early diagnosis of chronic obstructive pulmonary disease (COPD) and asthma. Although post-bronchodilator airflow limitation is essential for definite diagnosis of COPD and post bronchodilator normalization of airflow is suggestive of asthma, this test has not been prevailed in health checkup. The objective of this study was to estimate the prevalence of airflow limitation defined by pre- and post-bronchodilator spirometry in health checkup. Post-bronchodilator spirometry was conducted for participants with airflow limitation in a town-wide health checkup for residents aged 40 years and older in Hisayama, a town in the western part of Japan. The prevalence of pre- and post-bronchodilator airway limitation defined by FEV1/FVC < 70% were estimated. A total of 2,232 participants underwent pre-bronchodilator spirometry. In males, the age of current smokers was significantly younger than those of never smokers and former smokers. In females, the ages of current- and former smokers were significantly younger than never smokers. The values of %FEV1 and %FVC in current smokers were significantly lower than those in former smokers and never smokers. Two hundred sixty nine subjects, 85% of total subjects with a pre-bronchodilator FEV1/FVC < 70%, completed post-bronchodilator spirometry. The prevalence of pre-bronchodilator airflow limitation was 14.6% in males and 13.7% in females, and the prevalence of post-bronchodilator airway limitation was 8.7% and 8.7%, respectively. Post-bronchodilator spirometry in health checkup would reduce the number of subjects with probable COPD to two-third. Recommendation for those examinees to take further evaluations may pave the way for early intervention. PMID- 26888698 TI - Single-Incision Laparoscopic Cholecystectomy: our experience and review of literature. AB - AIM: After the revolution in the surgery of gallbladder stones represented by the laparoscopic cholecystectomy, we tried a new technique that further maximize the aesthetic results and that at the same time is of easy learning for young surgeons. PATIENTS AND METHODS: From January 2011 to December 2012 we performed at our department 320 cholecystectomy: 27 in laparotomy and 293 in laparoscopy. Of these, 88 underwent to Single Incision Laparoscopic Surgery (SILS), namely the Single Incision Laparoscopic Cholecystectomy (SILC), in recruited patients aged between 19-65 years; 56 patients were females and 32 were males. RESULTS: The laparoscopic cholecystectomy with the SILS methodology is a safe technique. Respect to multi-port Laparoscopic Cholecystectomy (LC), we have cosmetic advances. The pain is less in extraumbilical sites, and the major umbilical pain can be prevented by local anaesthesia. The times are slightly longer, especially at the beginning of training, but after a few of operations it is reduced to about one hour. We didn't found any other difference in vantage and advantage between the two technics, only a case of postoperative umbilical hernia in SILS. CONCLUSION: We found the SILS a safe and effective technique for the cholecystectomy. PMID- 26888699 TI - Endoscopic treatment of superficial colorectal neoplasms. Retrospective analysis of a single center technique and results. AB - Endoscopic Submucosal Dissection (ESD) is a technique developed in Japan for "en bloc" resection of larger superficial neoplasms of the gastrointestinal tract as an alternative to the traditional Endoscopic Mucosal Resection (EMR), with removal of the lesion in multiple fragments ("piecemeal"). ESD offers a lower recurrence rate and allows a more accurate histopathological examination. This procedure is however considered technically difficult and therefore requires an adequate learning curve, it is time consuming with more discomfort for the patient, it has a higher complication rate, it is more expensive. To overcome these disadvantages, in the Western countries a hybrid technique called Circumferential Submucosal Incision - Endoscopic Mucosal Resection (CSI-EMR) has been developed and is especially employed for colonic lesions. This article analyzes retrospectively the results obtained in a single centre by a single operator in the treatment of 23 patients (12 men and 11 women, average age 65,6 years), all suffering from superficial, larger than >= 20 mm colorectal neoplasms: 9 were treated with ESD for rectal lesions and 14 were treated with CSI-EMR for colonic lesions. Findings show a technical success rate of 66,6% for ESD and 78,5% for CSI-EM, and a 0% recurrence rate during follow-up, 4,3% bleeding and 13% perforation complications. The histology of the removed lesions showed 13 (56,5%) low grade dysplasia adenomas, 8 (34,7%) high grade dysplasia adenomas, one grade 1 sigmoid colon adenocarcinoma infiltrating the submucosal layer without lymphovascular invasion, with free margins (R0), treated conservatively, and one grade 1 cecum adenocarcinoma, infiltrating the submucosal layer, with lymphovascular invasion and involved excision margin, treated surgically with no residual neoplastic disease in the surgical specimen. These data are in line with the most significant ones in literature, except for the higher complication rate, which the authors ascribe to the "learning curve" and the smaller number of treated patients. PMID- 26888701 TI - Differentiated thyroid cancer: feasibility of loboisthmectomy in an endemic region. AB - AIM: The aim of the present retrospective study was to assess the feasibility of loboisthmectomy for the treatment of differentiated thyroid cancer in a endemic area, evaluating the histopathological features and the results of a case series of 1154 patients. PATIENTS AND METHODS: The clinical records of 1154 patients submitted to total thyroidectomy in our Department were retrospectively reviewed to analyze the histopathological characters and the results. RESULTS: In 1044 cases (90.5%) a papillary cancer was observed, in 110 (9.5%) a follicular carcinoma; microcarcinomas were 399 (34.5%). Multifocality was present in 323 cases (28%), in 142 unilateral (12.3%) and in 181 bilateral (15.7%). Thyroiditis coexisted in 472 patients (40.9%), multinodular goiter in 404 (35%), Graves' disease in 48 (4.1%), and multinodular toxic goiter in 38 (3.3%). Complications were: postoperative bleeding in 20 patients (1.7%), transient unilateral vocal cord paralysis in 20 (1.7%) definitive in 10 (0.86%), a transient bilateral paralysis in 1 (0.08%), a transient hypoparathyroidism in 351 (30.4%), and a definitive in 24 (2.07%). Nodal recurrence occurred in 25 patients (2.16%). CONCLUSIONS: Total thyroidectomy remains the safest treatment in differentiated thyroid cancer, especially if performed in high volume centers in which complications can be minimized. Loboisthmectomy can be a viable and safe alternative in small (< 1 cm) unifocal tumors in patients at low risk. Loboisthmectomy is limited in endemic areas by the association with other thyroid diseases. A correct and detailed information of the patient is essential before planning surgery. PMID- 26888700 TI - Hydronephrosis and utero-vaginal prolapse in postmenopausal women: management and treatment. AB - INTRODUCTION: Pelvic organ prolapse is a multifactorial disease. Aim was to evaluate the effect of the whole surgical correction of pelvic floor on hydronephrosis due to severe prolapse. PATIENTS AND METHODS: A retrospective case study on 250 patients presenting with severe uterovaginal prolapse was carried out. RESULTS: Hydronephrosis was found in 32/234 (13.7 %). All patients underwent hysterectomy, vaginal apex axial suspension, posterior and anterior repair, vaginally. Prepubic TICT (Tension free Incontinence Cystocoele Treatment) was done in 38 cases (3 with hydronephrosis). Of the 32/234 (13.7 %) patients with hydronephrosis, 18/32 (56.25%) had complete resolution of hydronephrosis after treatment, 14/32 (43.75%) had a reduction of calico-pyelic dilatation, among them 8 patients had a second degree and 6 a first degree of hydronephrosis. CONCLUSIONS: Vaginal-hysterectomy, axial apex suspension, anterior and posterior repair resulted in either complete resolution or improvement of hydronephrosis. Prepubic TICT did not interfere on mechanical obstruction and maintained postoperative continence in the event of occult Stress Urinary Incontinence (SUI). PMID- 26888702 TI - An audit of consenting practices in a district general hospital. Can we improve? AB - INTRODUCTION: Informed consent, as the declaration of patients' will, forms the basis of legality of medical procedures. A standard form based on the Department of Health model is widely used in the National Health Service (NHS). The aim of this audit process was to assess the current consent practice in comparison to the UK's General Medical Council guidance and local policy and make any appropriate improvements. PATIENTS AND METHODS: 254 adult consent forms were reviewed during the patients' admission. Data collected included legible documentation, grade of health professional completing the consent form, providing additional written information, use of abbreviations, securing the consent form in the medical records and, providing a copy to the patient. After initial assessment, interventions in an attempt to improve adherence to guidelines were introduced. A repeat audit of a further set of 110 notes was completed to assess the effectiveness of our interventions. RESULTS: Our baseline assessment of 254 consent forms comprised of 198 (78%) elective and 56 (22%) emergency procedures. 87 (34%) consent forms were secure in the medical records. Grade of health professional was recorded in 211 (83%). 191 (75%) forms were legible. 48 (19%) patients were given copy of the consent. Only 24 (9%) patients were given additional written information. Abbreviations were used in 68 (27%) forms. Only 12 (5%) of consent forms met all criteria simultaneously. Re-audit after intervention assessed 110 consent forms; 30 (27%) for elective and 80 (72%) for emergency procedures. 52 (47%) of consent forms were secure in medical records, grade of health professional was recorded in 94 (85%), 101 (75%) forms were legible, 42 (38%) patients received copy of consent and 41 (37%) of patients received additional written information. CONCLUSION: Initially only 5% of consent forms completely met GMC guidelines. This demonstrates an alarmingly poor adherence to such guidance that plays a vital role in patient safety, patient ethics autonomy, not to mention potential medico-legal and clinical governance implications for surgical practice. Our intervention has improved the quality of consenting within our hospital according to these guidelines. With these interventions set to continue and further develop, we expect that the quality of the consenting process will continue to provide patients with all that it is designed to. PMID- 26888703 TI - Arterial endofibrosis in professional cyclists. AB - External Iliac Artery Endofibrosis (EIAE) is an uncommon disease usually affecting young, otherwise healthy, patients. It usually involves cyclists but cases have been reported in other groups of endurance athletes. The external iliac artery is the most affected anatomical site but other locations are described too. The precise pathophysiology and long-term evolution of the disease still remain unknown. The diagnosis may be challenging and delayed as the patients usually present symptoms only in extreme conditions and physical and instrumental examinations may be normal at rest. We present two cases of young professional cyclists who suffered of exercise-induced leg pain which led them to reduce running. Both patients were firstly treated with balloon angioplasty that rapidly failed to improve their symptoms. The successive open surgery with endofibrosectomy and autologous saphenous vein closure patch completely resolved physical limitations. EIAE is a rare disease that can induce arterial stenosis, thrombosis, dissection and secondary atheroma. After-exercise ankle-brachial index represents a useful diagnostic criterion. Careful observation of angio-CT may strengthen the suspect. Knowledge of the these features allows a better pre operative assessment and an early effective treatment. Surgical revascularization remains the gold standard approach. PMID- 26888704 TI - Subcutaneous cervical emphysema and pneumomediastinum due to a diastatic rupture of the cecum. AB - Pneumomediastinum usually occurs after esophageal or chest trauma. Subcutaneous cervical emphysema as a presentation of non-traumatic colonic perforation following colorectal cancer or diverticulitis, is very rare. We report a case of a patient with rectal cancer who developed a diastatic cecum retroperitoneal perforation with a secondary pneumomediastinum and cervical emphysema. The patient was in treatment with a neoadjuvant chemo-radiotherapy for a low rectal cancer. Treatment consisted in an emergency right hemi-colectomy with ileostomy and performance of distal colonic fistula. The Authors discuss the occurrence of pneumomediastinum and cervical emphysema complicating rectal cancer, pointing out ethiopathogenesis, clinical presentation, diagnosis and treatment. The importance of performing a diverting colostomy when neoadjuvant chemotherapy is scheduled in patients with stenotic rectal cancer, although not clinically occluded. PMID- 26888705 TI - Appendicular mucocele: two case reports and literature review. AB - The classification of mucinous tumors of the vermiform appendix is quite controversial, and includes a spectrum of neoplastic lesions ranging from benign proliferations, intraluminal, to invasive adenocarcinomas. Among the complications of appendicular mucinous neoplasms we should mention the "pseudomyxoma peritonei", a condition caused by cancerous cells (mucinous adenocarcinoma) that produce abundant mucin or gelationous ascites. Mucinous neoplasms of the appendix are rare diseases of unknown etiology. The diagnosis is difficult because of poorly specific clinical, biochemical and imaging parameters, and their detection can be occasional. Most of the reported cases involving women of reproductive age (with a history of endometriosis, abdominal surgery or pelvic inflammatory disease). The definitive diagnosis requires histology and immunohistochemistry. Cytoredutive surgery combined with hyperthermic intraperitoneal chemoterapy (HIPEC) is now considered the best treatment for this disease. We present two cases treated with surgery and HIPEC. PMID- 26888707 TI - [Rectal neuroendocrine tumors: surgical therapy]. AB - The incidence of rectal neuroendocrine tumors (NET) has increased in recent years. Most of these neoplasms are asymptomatic and are diagnosed by colonoscopy screening, which could be one of the reasons for the increasing occurrence. As less than 1 % of rectal NET produce serotonin they are practically never discovered due to a carcinoid syndrome. The current guidelines of the European (ENETS) and North American (NANETS) Neuroendocrine Tumor Societies support clinicians with useful diagnostic and treatment algorithms. The most important criteria for therapy are tumor size and histopathological risk factors for metastases. For well-differentiated rectal neuroendocrine neoplasms < 1 cm, local endoscopic or surgical excision is recommended. Due to the lack of evidence tumors sized 1-2 cm represent a grey area for prognosis and treatment. All NET > 1.5 cm must be excised by radical surgery as low anterior rectal resection or abdominoperineal extirpation with total mesorectal excision (TME). Resectable liver and lung metastases of well-differentiated NETs should be surgically treated with curative intent. PMID- 26888708 TI - Adipose stem cells differentiated chondrocytes regenerate damaged cartilage in rat model of osteoarthritis. AB - Transplantation of mesenchymal stem cells (MSCs) or autologous chondrocytes has been shown to repair damages to articular cartilage due to osteoarthritis (OA). However, survival of transplanted cells is considerably reduced in the osteoarthritic environment and it affects successful outcome of the transplantation of the cells. Differentiated chrondroytes derived from adipose stem cells have been proposed as an alternative source and our study investigated this possibility in rats. We investigated the regenerative potential of ADSCs and DCs in osteoarthritic environment in the repair of cartilage in rats. We found that ADSCs maintained fibroblast morphology in vitro and also expressed CD90 and CD29. Furthermore, ADSCs differentiated into chondrocytes, accompanied by increased level of proteoglycans and expression of chondrocytes specific genes, such as, Acan, and Col2a1. Histological examination of transplanted knee joints showed regeneration of cartilage tissue compared to control OA knee joints. Increase in gene expression for Acan, Col2a1 with concomitant decrease in the expression of Col1a1 suggested formation of hyaline like cartilage. A significant increase in differentiation index was observed in DCs and ADSCs transplanted knee joints (P = 0.0110 vs. P = 0.0429) when compared to that in OA control knee joints. Furthermore, transplanted DCs showed increased proliferation along with reduction in apoptosis as compared to untreated control. In conclusion, DCs showed better survival and regeneration potential as compared with ADSCs in rat model of OA and thus may serve a better option for regeneration of osteoarthritic cartilage. PMID- 26888709 TI - Growth monitoring and the prognosis of mortality in low-income settings. PMID- 26888710 TI - Intake of whole grains is associated with lower risk of myocardial infarction: the Danish Diet, Cancer and Health Cohort. AB - BACKGROUND: High intake of whole grains has been associated with lower risk of coronary heart disease; however, the research that has been used to evaluate different effects of different whole-grain cereals (e.g., wheat, rye, and oats) has been sparse. OBJECTIVE: We investigated the association between whole-grain intake in terms of total intake and intakes of different cereals and myocardial infarction. DESIGN: This prospective study included 54,871 Danish adults aged 50 64 y, of whom 2329 individuals developed myocardial infarction (13.6 y of follow up). Detailed information on daily intake of whole-grain products was available from a self-administered food-frequency questionnaire, and intakes of total whole grain and whole-grain species (wheat, rye, and oats) were estimated. The association between intake of whole grains and risk of myocardial infarction was examined with the use of a Cox proportional hazards model adjusted for potential confounders. RESULTS: For both men and women with total whole-grain intake in the highest quartile, lower risks of myocardial infarction were shown [HRs: 0.75 (95% CI: 0.65, 0.86) and 0.73 (95% CI: 0.58, 0.91), respectively] than for individuals with intake in the lowest quartile. When the specific cereal species were considered, rye and oats, but not wheat, were associated with lower myocardial infarction risk in men. No significant associations were seen in women. For total whole-grain products, significantly lower myocardial infarction risks were seen with higher intakes in both men and women. Rye bread (in men and women) and oatmeal (in men) were associated with significantly lower risk of myocardial infarction, whereas no significant association was shown for whole-grain bread, crispbread, and wheat. CONCLUSION: In this study, we provide support for the hypothesis that whole-grain intake is related to lower risk of myocardial infarction and suggest that the cereals rye and oats might especially hold a beneficial effect. PMID- 26888711 TI - On the need for improved methodologic quality of published reviews. PMID- 26888712 TI - Energy depletion by diet or aerobic exercise alone: impact of energy deficit modality on appetite parameters. AB - BACKGROUND: Millions of Americans attempt to lose weight each year, and it is unclear whether the modality of acute, tightly controlled energy depletions can differently affect appetite parameters and olfaction. OBJECTIVE: The objectives were to examine how the modality of an acute 3-d isocaloric 25% energy depletion by dieting alone or by aerobic exercise alone differently affects appetite and appetite-related hormones, ad libitum feeding, food reward (snack points), and olfaction. DESIGN: Ten male participants with a mean +/- SD age of 23.7 +/- 5.1 y and an initial mean +/- SD body weight of 83.2 +/- 11.5 kg participated in this randomized crossover design. Baseline measurement [day 1 of the control condition (CON1)] was performed and repeated 3 d later [day 4 of the control condition (CON4)], after which randomization was applied to the order of the 2 experimental conditions: 25% daily needs energy deficits induced by diet only (DIET) and by exercise only (EX) and tested before [day 1 of DIET (DIET1) and day 1 of EX (EX1)] and after 3 d [day 4 of DIET (DIET4) and day 4 of EX (EX4)] of the intervention. Body weight, leptin and ghrelin concentrations, relative reinforcing value of food, and olfaction were measured at days 1 and 4. Body composition (dual-energy X-ray absorptiometry), ad libitum energy intake (EI; buffet), and palatability (visual analog scale) were measured only at day 4. RESULTS: Relative to CON4, EI (P= 0.001), palatability (P= 0.01), and odor threshold (P= 0.05) were higher at DIET4; relative to CON4, palatability (P= 0.03) was higher at EX4. Compared with EX4, EI was higher for DIET4 (P= 0.006). Relative to CON4, snack points earned were higher at DIET4 (P= 0.03) and EX4 (P= 0.001); more snack points were earned at EX4 relative to DIET4 (P= 0.001). CONCLUSIONS: Compared with the control condition, DIET represented a greater acute challenge to appetite regulation than EX, as demonstrated by greater appetite and ad libitum EI. This study confirms that compared with depletions by exercise alone, acute caloric restriction results in rapid changes in appetite that result in compensatory eating, which may initially dissuade potential success in weight-loss efforts. This trial was registered at clinicaltrials.gov as NCT02653378. PMID- 26888715 TI - Characterisation and application of Halomonas shantousis SWA25, a halotolerant bacterium with multiple biogenic amine degradation activity. AB - Biogenic amines are identified as toxicological substances in foods and may have detrimental effects on consumers' health. In recent years, the application of microorganisms that can degrade biogenic amines has become an emerging method for their reduction. The degradation characteristics and application potential of a salt-tolerant bacterium Halomonas shantousis SWA25 were investigated in this study. H. shantousis SWA25 exhibited degradation activity against eight biogenic amines at 10-40 degrees C (optimum, 30-40 degrees C) and pH 3.0-9.0 (optimum, 6.0 7.0) in the presence of 0-20% (w/v) NaCl (optimum, 0%). Specifically, H. shantousis SWA25 degraded all tryptamine (TRY) and tyramine (TYR) in 6 h, all phenethylamine (PHE) in 9 h, 66.7% of histamine (HIM), 52.4% of cadaverine (CAD), 48.0% of spermidine (SPD), 42.9% of putrescine (PUT) and 42.0% of spermine (SPM) in 20 h at 30 degrees C and pH 7.0 with shaking at 120 r min-1. The enzymes from H. shantousis SWA25 responsible for degradation of biogenic amines were mainly amine oxidases located on the cell membrane. Further studies showed that H. shantousis SWA25 effectively degraded TRY, PHE, PUT, CAD, HIM and TYR in commercial fish sauce and soy sauce samples. Nevertheless, significant SPD and SPM degradation were not observed due to low initial concentrations. Therefore, H. shantousis SWA25 can be applied as a potential biogenic amines degradation bacterium in foods. PMID- 26888713 TI - FTO genotype and weight loss in diet and lifestyle interventions: a systematic review and meta-analysis. AB - BACKGROUND: Studies have suggested that the fat mass and obesity-associated (FTO) genotype is associated with individual variability in weight loss in response to diet/lifestyle interventions, but results are inconsistent. OBJECTIVE: We aimed to provide a summary of the literature evaluating the relation between the FTO genotype and weight loss in response to diet/lifestyle interventions. DESIGN: A search of English-language articles in the PubMed and Embase databases (through 30 April 2015) was performed. Eligible studies were diet/lifestyle weight-loss intervention studies conducted in adults that reported changes in body weight or body mass index (BMI) by the FTO variant rs9939609 (or its proxy). Differences in weight loss between FTO genotypes across studies were pooled with the use of fixed-effect models. RESULTS: A meta-analysis of 10 studies (comprising 6951 participants) that reported the results of additive genetic models showed that individuals with the FTO TA genotype and AA genotype (those with the obesity predisposing A allele) had 0.18-kg (95% CI: -0.09-, 0.45-kg;P= 0.19; NS) and 0.44 kg (95% CI: 0.09-, 0.79-kg;P= 0.015) greater weight loss, respectively, than those with the TT genotype. A meta-analysis of 14 studies (comprising 7700 participants) that reported the results of dominant genetic models indicated a 0.20-kg (-0.43-, 0.04-kg) greater weight loss in the TA/AA genotype than in the TT genotype (P= 0.10). In addition, differences in weight loss between the AA genotype and TT genotype were significant in studies with a diet intervention only, adjustment for baseline BMI or body weight, and several other subgroups. However, the relatively small number of studies limited these stratified analyses, and there was no statistically significant difference between subgroups. CONCLUSIONS: This meta-analysis suggests that individuals carrying the homozygous FTO obesity-predisposing allele may lose more weight through diet/lifestyle interventions than noncarriers. Our data provide evidence for genetic variability in response to diet/lifestyle interventions on weight loss, although clinical applications of these findings need further investigations. PMID- 26888714 TI - Comparison of multiple methods to measure maternal fat mass in late gestation. AB - BACKGROUND: Measurements of maternal fat mass (FM) are important for studies of maternal and fetal health. Common methods of estimating FM have not been previously compared in pregnancy with measurements using more complete body composition models. OBJECTIVES: The goal of this pilot study was to compare multiple methods that estimate FM, including 2-, 3- and 4-compartment models in pregnant women at term, and to determine how these measures compare with FM by dual-energy X-ray absorptiometry (DXA) 2 wk postpartum. DESIGN: Forty-one healthy pregnant women with prepregnancy body mass index (in kg/m(2)) 19 to 46 underwent skinfold thickness (SFT), bioelectrical impedance analysis (BIA), body density (Db) via air displacement plethysmography (ADP), and deuterium dilution of total body water (TBW) with and without adjustments for gestational age using van Raaij (VRJ) equations at 37-38 wk of gestation and 2 wk postpartum to derive 8 estimates of maternal FM. Deming regression analysis and Bland-Altman plots were used to compare methods of FM assessment. RESULTS: Systematic differences in FM estimates were found. Methods for FM estimates from lowest to highest were 4 compartment, DXA, TBW(VRJ), 3-compartment, Db(VRJ), BIA, air displacement plethysmography body density, and SFT ranging from a mean +/- SD of 29.5 +/- 13.2 kg via 4-compartment to 39.1 +/- 11.7 kg via SFT. Compared with postpartum DXA values, Deming regressions revealed no substantial departures from trend lines in maternal FM in late pregnancy for any of the methods. The 4-compartment method showed substantial negative (underestimating) constant bias, and the air displacement plethysmography body density and SFT methods showed positive (overestimating) constant bias. ADP via Db(VRJ)and 3-compartment methods had the highest precision; BIA had the lowest. CONCLUSIONS: ADP that uses gestational age specific equations may provide a reasonable and practical measurement of maternal FM across a spectrum of body weights in late pregnancy. SFT would be acceptable for use in larger studies. This trial was registered at clinicaltrials.gov as NCT02586714. PMID- 26888716 TI - Development of Real-Time RT-PCR Assays for Detection and Typing of Epizootic Haemorrhagic Disease Virus. AB - Epizootic haemorrhagic disease virus (EHDV) is an emerging arboviral pathogen of wild and domestic ruminants worldwide. It is closely related to bluetongue virus (BTV) and is transmitted by adult females of competent Culicoides vector species. The EHDV genome consists of ten linear double-stranded (ds)RNA segments, encoding five non-structural and seven structural proteins. Genome-segment reassortment contributes to a high level of genetic variation in individual virus strains, particularly in the areas where multiple and distinct virus lineages co circulate. In spite of the relatively close relationship between BTV and EHDV herd-immunity to BTV does not appear to protect against the introduction and infection of animals by EHDV. Although EHDV can cause up to 80% morbidity in affected animals, vaccination with the homologous EHDV serotype is protective. Outer-capsid protein VP2, encoded by Seg-2, is the most variable of the EHDV proteins and determines both the specificity of reactions with neutralizing antibodies and consequently the identity of the eight EHDV serotypes. In contrast, VP6 (the viral helicase), encoded by Seg-9, is highly conserved, representing a virus species/serogroup-specific antigen. We report the development and evaluation of quantitative (q)RT-PCR assays targeting EHDV Seg-9 that can detect all EHDV strains (regardless of geographic origin/topotype/serotype), as well as type-specific assays targeting Seg-2 of the eight EHDV serotypes. The assays were evaluated using orbivirus isolates from the 'Orbivirus reference collection' (ORC) at The Pirbright Institute and were shown to be EHDV pan-reactive or type-specific. They can be used for rapid, sensitive and reliable detection and identification (typing) of EHDV RNA from infected blood, tissue samples, homogenized Culicoides, or tissue culture supernatant. None of the assays detected RNA from closely related but heterologous orbiviruses, or from uninfected host animals or cell cultures. The techniques presented could be used for both surveillance and vaccine matching (serotype identification) as part of control strategies for incursions in wild and domestic animal species. PMID- 26888717 TI - AST: Activity-Security-Trust driven modeling of time varying networks. AB - Network modeling is a flexible mathematical structure that enables to identify statistical regularities and structural principles hidden in complex systems. The majority of recent driving forces in modeling complex networks are originated from activity, in which an activity potential of a time invariant function is introduced to identify agents' interactions and to construct an activity-driven model. However, the new-emerging network evolutions are already deeply coupled with not only the explicit factors (e.g. activity) but also the implicit considerations (e.g. security and trust), so more intrinsic driving forces behind should be integrated into the modeling of time varying networks. The agents undoubtedly seek to build a time-dependent trade-off among activity, security, and trust in generating a new connection to another. Thus, we reasonably propose the Activity-Security-Trust (AST) driven model through synthetically considering the explicit and implicit driving forces (e.g. activity, security, and trust) underlying the decision process. AST-driven model facilitates to more accurately capture highly dynamical network behaviors and figure out the complex evolution process, allowing a profound understanding of the effects of security and trust in driving network evolution, and improving the biases induced by only involving activity representations in analyzing the dynamical processes. PMID- 26888720 TI - Magnetic effects in sulfur-decorated graphene. AB - The interaction between two different materials can present novel phenomena that are quite different from the physical properties observed when each material stands alone. Strong electronic correlations, such as magnetism and superconductivity, can be produced as the result of enhanced Coulomb interactions between electrons. Two-dimensional materials are powerful candidates to search for the novel phenomena because of the easiness of arranging them and modifying their properties accordingly. In this work, we report magnetic effects in graphene, a prototypical non-magnetic two-dimensional semi-metal, in the proximity with sulfur, a diamagnetic insulator. In contrast to the well-defined metallic behaviour of clean graphene, an energy gap develops at the Fermi energy for the graphene/sulfur compound with decreasing temperature. This is accompanied by a steep increase of the resistance, a sign change of the slope in the magneto resistance between high and low fields, and magnetic hysteresis. A possible origin of the observed electronic and magnetic responses is discussed in terms of the onset of low-temperature magnetic ordering. These results provide intriguing insights on the search for novel quantum phases in graphene-based compounds. PMID- 26888721 TI - Nitrogen-doped Carbon Microfiber with Wrinkled Surface for High Performance Supercapacitors. AB - In this work, nitrogen-doped carbon microfiber (NCMF) is fabricated via a facile co-assembly of natural silk and graphene oxide (GO) and the following thermal treatment. The amphiphilic nature of GO endows NCMF a crumpled surface with a high surface area of 115 m(2) g(-1). As the binder-free electrode in electrical double-layer capacitors, NCMF shows an excellent capacitance of 196 F g(-1) at scan rate of 5 mV s(-1), which is almost four times higher than that of the pristine CMF from silk (55 F g(-1)). Additionally, the capacitance of NCMF can be kept around 92 F g(-1) at a high scan rate of 300 mV s(-1) even after 10000 cycles. More importantly, a high energy density (~ 22.7 MUW h cm(-2)) and power density (~ 10.26 mW cm(-2)) are achieved by the all-solid-state supercapacitor based on NCMF. PMID- 26888722 TI - Erratum to: Vaccination with ErbB-2 peptides prevents cancer stem cell expansion and suppresses the development of spontaneous tumors in MMTV-PyMT transgenic mice. PMID- 26888719 TI - Human Vascular Microphysiological System for in vitro Drug Screening. AB - In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400-800 MUM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction, and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-N(G)-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-alpha which had a transient effect upon acetylcholine-induced relaxation, and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 MUM lovastatin for three days prior to addition of Tumor necrosis factor - alpha (TNF-alpha) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli. PMID- 26888723 TI - Low prevalence of HER2 positivity amongst BRCA1 and BRCA2 mutation carriers and in primary BRCA screens. AB - The aim of this study is to delineate more clearly the prevalence of HER2+ breast cancer in women with germline BRCA1/2 mutations. For this purpose, we analysed primary mutation screens on women with breast cancer with unequivocal HER2 amplification and assessed the proportion of BRCA1 and BRCA2 breast cancers that were HER2+ comparing this with the existing literature. The results are that 1063 primary BRCA screens had confirmed tumour HER2 status. If HER2+ only 2.5 % (4/156) and 3.2 % (5/156) of women had a BRCA1 or BRCA2 mutation identified respectively; compared to 27.7 % (115/415) and 8.2 % (34/415) with triple negative tumours. Only 2.1 % (4/195) women with BRCA1-related breast cancer had HER2 amplified breast cancers rising to 6.8 % (n = 12, p = 0.04) in BRCA2. These rates are in keeping with most of the existing literature except a recent large multicenter report which documented higher rates but with no control group. The study concluded that true HER2-amplified breast cancers are rare amongst BRCA1 mutation carriers and are less common in BRCA2 than background rates. PMID- 26888724 TI - Perspectives on the provision of GDM screening in general practice versus the hospital setting: a qualitative study of providers and patients. AB - OBJECTIVE: A novel gestational diabetes mellitus (GDM) screening programme which involved offering screening at the patient's general practitioner (GP) compared with the traditional hospital setting was trialled. This study investigates perspectives of involved stakeholders on the provision of GDM screening at both settings. DESIGN: Thematic analysis of the perspectives of stakeholders involved in the receiving and provision of GDM screening in both the GP and hospital settings drawn from focus groups and interviews. PARTICIPANTS: 3 groups of participants are included in this research--patient participants, GP screening providers and hospital screening providers. All were recruited from a larger sample who participated in a randomised controlled screening trial. Purposeful sampling was utilised to select participants with a wide variety of perspectives on the provision of GDM screening. SETTING: Participants were recruited from a geographical area covered by 3 hospitals in Ireland. RESULTS: 4 themes emerged from thematic analysis--namely (1) travel distance, (2) best care provision, (3) sense of ease created and (4) optimal screening. CONCLUSIONS: The influence of travel distance from the screening site is the most important factor influencing willingness to attend for GDM screening among women who live a considerable distance from the hospital setting. For patients who live equidistance from both settings, other factors are important; namely the waiting facilities including parking, perceived expertise of screening provider personnel, access to emergency treatment if necessary, accuracy of tests and access to timely results and treatment. Optimal screening for GDM should be specialist led, incorporate expert advice of GDM screening, treatment and management, should be provided locally, offer adequate parking and comfort levels, provide accurate tests, and timely access to results and treatment. Such a service should result in improved rates of GDM screening uptake. TRIAL REGISTRATION NUMBER: ISRCTN41202110. PMID- 26888726 TI - How do scientists perceive the current publication culture? A qualitative focus group interview study among Dutch biomedical researchers. AB - OBJECTIVE: To investigate the biomedical scientist's perception of the prevailing publication culture. DESIGN: Qualitative focus group interview study. SETTING: Four university medical centres in the Netherlands. PARTICIPANTS: Three randomly selected groups of biomedical scientists (PhD, postdoctoral staff members and full professors). MAIN OUTCOME MEASURES: Main themes for discussion were selected by participants. RESULTS: Frequently perceived detrimental effects of contemporary publication culture were the strong focus on citation measures (like the Journal Impact Factor and the H-index), gift and ghost authorships and the order of authors, the peer review process, competition, the funding system and publication bias. These themes were generally associated with detrimental and undesirable effects on publication practices and on the validity of reported results. Furthermore, senior scientists tended to display a more cynical perception of the publication culture than their junior colleagues. However, even among the PhD students and the postdoctoral fellows, the sentiment was quite negative. Positive perceptions of specific features of contemporary scientific and publication culture were rare. CONCLUSIONS: Our findings suggest that the current publication culture leads to negative sentiments, counterproductive stress levels and, most importantly, to questionable research practices among junior and senior biomedical scientists. PMID- 26888725 TI - Sleep duration and mortality in the elderly: a systematic review with meta analysis. AB - OBJECTIVE: The purpose of our study was to evaluate the association between short and long sleep duration and all-cause and cardiovascular mortality among elderly individuals. DESIGN: Systematic review and meta-analysis of population-based cohort studies. SETTING: Articles were retrieved from international and national electronic databases. STUDY SELECTION: Studies were identified in PubMed, EMBASE, LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographic Index on Health Sciences from Spain) and CAPES (PhD thesis repository) between 1980 and 2015. Studies which met all criteria were eligible: participants aged 60 years or over, assessment of sleep duration as 24 h, nighttime or daytime sleep, evaluation of all-cause or cause-specific mortality, population-based cohort studies conducted on representative samples. There was no language restriction and studies published as abstracts were excluded. DATA EXTRACTION: Data were analysed using the Comprehensive Meta-Analysis software (V.3.3.070), and summary estimates (relative risk (RR), 95% CI) were calculated using a random effects model. Heterogeneity and consistency were evaluated through Cochran's Q and the I(2) statistics, respectively, and sensitivity analyses were conducted. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and cardiovascular mortality. RESULTS: Overall, 27 cohort studies were selected, comprising >70,000 elderly individuals, and followed up from 3.4 to 35 years. In the pooled analysis, long and short sleep duration were associated with increased all-cause mortality (RR 1.33; 95% CI 1.24 to 1.43 and RR 1.07; 95% CI 1.03 to 1.11, respectively), compared with the reference category. For cardiovascular mortality, the pooled relative risks were 1.43 (95% CI 1.15 to 1.78) for long sleep, and 1.18 (95% CI 0.76 to 1.84) for short sleep. Daytime napping >= 30 min was associated with risk of all-cause mortality (RR 1.27; 95% CI 1.08 to 1.49), compared with no daytime sleep, but longer sleep duration (>= 2.0 h) was not (RR 1.34; 95% CI 1.95 to 1.90). CONCLUSIONS: Among elderly individuals, long and short sleep duration are associated with increased risk for all-cause mortality. Long sleep duration is associated with cardiovascular mortality. PMID- 26888728 TI - Correction. PMID- 26888727 TI - Clinical outcomes in 995 unselected real-world patients treated with an ultrathin biodegradable polymer-coated sirolimus-eluting stent: 12-month results from the FLEX Registry. AB - OBJECTIVES: To evaluate, in the FLEX Registry, clinical outcomes of an ultrathin (60 um) biodegradable polymer-coated Supraflex sirolimus-eluting stent (SES) for the treatment of coronary artery disease. Additionally, to determine the vascular response to the Supraflex SES through optical coherence tomography (OCT) analysis. SETTING: Multicentre, single-arm, all-comers, observational registry of patients who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India. PARTICIPANTS: 995 patients (1242 lesions) who were treated with the Supraflex SES, between July 2013 and May 2014, at nine different centres in India. A total of 47 participants underwent OCT analysis at 6 months' follow-up. INTERVENTIONS: Percutaneous coronary intervention with Supraflex SES, PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint-the rate of major adverse cardiac events (defined as a composite of cardiac death, myocardial infarction (MI), target lesion revascularisation (TLR))-was analysed during 12 months. RESULTS: At 12 months, the primary endpoint occurred in 36 (3.7%) of 980 patients, consisting of 18 (1.8%) cardiac deaths, 16 (1.6%) MI, 7 (0.7%) TLR and 2 (0.2%) cases of non-target lesion target vessel revascularization. In a subset of 47 patients, 1227 cross-sections (9309 struts) were analysed at 6 months by OCT. Overall, a high percentage of struts was covered (98.1%), with a mean neointimal thickness of 0.13 +/- 0.06 um. CONCLUSIONS: The FLEX Registry evaluated clinical outcomes in real-world and more complex cohorts and thus provides evidence that the Supraflex SEX can be used safely and routinely in a broader percutaneous coronary intervention population. Also, the Supraflex SES showed high percentage of stent strut coverage and good stent apposition during OCT follow-up. PMID- 26888729 TI - Understanding vulnerability to self-harm in times of economic hardship and austerity: a qualitative study. AB - OBJECTIVE: Self-harm and suicide increase in times of economic recession, but little is known about why people self-harm when in financial difficulty, and in what circumstances self-harm occurs. This study aimed to understand events and experiences leading to the episode of self-harm and to identify opportunities for prevention or mitigation of distress. SETTING: Participants' homes or university rooms. PARTICIPANTS: 19 people who had attended hospital following self-harm in two UK cities and who specifically cited job loss, economic hardship or the impact of austerity measures as a causal or contributory factor. PRIMARY AND SECONDARY OUTCOME MEASURES: Semistructured, in-depth interviews. Interviews were audio recorded, transcribed and analysed cross-sectionally and as case studies. RESULTS: Study participants described experiences of severe economic hardship; being unable to find employment or losing jobs, debt, housing problems and benefit sanctions. In many cases problems accumulated and felt unresolvable. For others an event, such as a call from a debt collector or benefit change triggered the self-harm. Participants also reported other current or past difficulties, including abuse, neglect, bullying, domestic violence, mental health problems, relationship difficulties, bereavements and low self-esteem. These contributed to their sense of despair and worthlessness and increased their vulnerability to self-harm. Participants struggled to gain the practical help they felt they needed for their economic difficulties or therapeutic support that might have helped with their other co-existing or historically damaging experiences. CONCLUSIONS: Economic hardships resulting from the recession and austerity measures accumulated or acted as a 'final straw' to trigger self-harm, often in the context of co-existing or historically damaging life-experiences. Interventions to mitigate these effects should include providing practical advice about economic issues before difficulties become insurmountable and providing appropriate psychosocial support for vulnerable individuals. PMID- 26888730 TI - Acknowledging unreported problems with active surveillance for prostate cancer: a prospective single-centre observational study. AB - OBJECTIVE: To report outcomes of patients with localised prostate cancer (PCa) managed with active surveillance (AS) in a standard clinical setting. DESIGN: Single-centre, prospective, observational study. SETTING: Non-academic, average size hospital in Switzerland. PARTICIPANTS: Prospective, observational study at a non-academic, average-size hospital in Switzerland. Inclusion and progression criteria meet general recommendations. 157 patients at a median age of 67 (61-70) years were included from December 1999 to March 2012. Follow-up (FU) ended June 2013. RESULTS: Median FU was 48 (30-84) months. Overall confirmed reclassification rate was 20% (32/157). 20 men underwent radical prostatectomy with 1 recurrence, 11 had radiation therapy with 2 prostate-specific antigen relapses, and 1 required primary hormone ablation with a fatal outcome. Kaplan Meier estimates for those remaining in the study showed an overall survival of 92%, cancer-specific survival of 99% and reclassification rate of 41%. Dropout rate was 36% and occurred at a median of 48 (21-81) months after inclusion. 68 (43%) men are still under AS. CONCLUSIONS: Careful administration of AS can and will yield excellent results in long-term management of PCa, and also helps physicians and patients alike to balance quality of life and mortality. Our data revealed significant dropout from FU. Patient non-compliance can be a relevant problem in AS. PMID- 26888731 TI - Treatment of faecal incontinence using allogeneic-adipose-derived mesenchymal stem cells: a study protocol for a pilot randomised controlled trial. AB - INTRODUCTION: Faecal incontinence is a distressing condition with recurrent uncontrolled passage of faecal material. Although faecal incontinence may cause psychological depression and social isolation, previous treatments have been limited. Recently, regenerative treatment has been developed using mesenchymal stem cells. Especially, there are possibilities that adipose-tissue-derived stem cells can be effective to treat a degenerated anal sphincter that is causing faecal incontinence. Therefore, this study aimed to investigate the safety and efficacy of using allogeneic-adipose-derived mesenchymal stem cells in the treatment of the anal sphincter of patients with faecal incontinence. METHODS AND ANALYSIS: This study is a randomised, prospective, dose escalation, placebo controlled, single-blinded, single-centre trial with two parallel groups. The safety test is performed by an injection of allogeneic-adipose-derived mesenchymal stem cells (ALLO-ASCs) into the anal sphincter with dose escalation (3 * 10(7), 6 * 10(7) and 9 * 10(7) cells, sequentially). After confirming the safety of the stem cells, an efficacy test is performed by this dose in the experimental group. The experimental group will receive ALLO-ASCs mixed with fibrin glue into the anal sphincter, and the placebo group will receive 0.9% normal saline injection mixed with fibrin glue. The primary end point is to assess the safety of ALLO-ASCs after the injection into the anal sphincter, and the secondary end point is to compare the efficacy of ALLO-ASC injection with fibrin glue in patients with faecal incontinence. ETHICS AND DISSEMINATION: The study protocol was approved by the Ministry of Food and Drug Safety and the Ministry of Health & Welfare, in the Republic of Korea. The informed consent form was approved by the institutional review board of Gangnam Severance Hospital (IRB approval number 3-2014-0271). Dissemination of the results will be presented at a conference and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT02384499; Pre-results. PMID- 26888733 TI - Children's experiences about a structured assessment of health-related quality of life during a patient encounter. AB - BACKGROUND: It has been stated that care for children with chronic health conditions tends to focus on condition-specific issues rather than how these children experience their health and everyday life functioning. AIM: The aim of this study was to explore children's experiences about a structured assessment of health-related quality of life applied during a patient encounter. METHODS: Prior to the start of the study, a clinical intervention based on the questionnaire DISABKIDS Chronic Generic Measure (DCGM-37) was performed. A qualitative explorative design was chosen, and 25 children between 10-17 years of age were interviewed after the consultation at four different paediatric outpatient clinics. Data were analysed according to qualitative content analysis. RESULTS: The results were twofold: children experienced that the assessment was providing them with insights about their health, which motivated them to make lifestyle changes. When outcomes were discussed and requested, the children felt encouraged. CONCLUSIONS: The use of an assessment of health-related quality of life may promote insights about health and encourage children with chronic health conditions to discuss their outcomes with healthcare professionals. PMID- 26888732 TI - Using Monte Carlo simulation to assess variability and uncertainty of tobacco consumption in a city by sewage epidemiology. AB - OBJECTIVE: To use Monte Carlo simulation to assess the uncertainty and variability of tobacco consumption through wastewater analysis in a city. METHODS: A total of 11 wastewater treatment plants (WWTPs) (serving 2.2 million people; approximately 83% of urban population in Dalian) were selected and sampled. By detection and quantification of principal metabolites of nicotine, cotinine (COT) and trans-3'-hydroxycotinine (OH-COT), in raw wastewater, back calculation of tobacco use in the population of WWTPs can be realised. RESULTS: COT and OH-COT were detected in the entire set of samples with an average concentration of 2.33 +/- 0.30 and 2.76 +/- 0.91 ug/L, respectively. The mass load of absorbed NIC during the sampling period ranged from 0.25 to 4.22 mg/day/capita with an average of 1.92 mg/day/capita. Using these data, we estimated that smokers in the sampling area consumed an average of 14.6 cigarettes per day for active smoker. Uncertainty and variability analysis by Monte Carlo simulation were used to refine this estimate: the procedure concluded that smokers in Dalian smoked between 10 and 27 cigarettes per day. This estimate showed good agreement with estimates from epidemiological research. CONCLUSIONS: Sewage-based epidemiology may be a useful additional tool for the large-scale monitoring of patterns of tobacco use. Probabilistic methods can be used to strengthen the reliability of estimated use generated from wastewater analysis. PMID- 26888734 TI - The evaluation of myocardial function of patients in the early stage of acute ischemic stroke by two-dimensional speckle tracking echocardiography. AB - PURPOSE: To evaluate the myocardial dysfunction in the early stage of nonhemorrhagic stroke and its association with the National Institutes of Health Stroke Scale (NIHSS) score, by two-dimensional speckle tracking echocardiography. METHODS: We included 29 patients with acute ischemic stroke, in whom NIHSS scores were calculated and stroke infarct volumes recorded. Within 48 hours of admission, cardiac evaluation with speckle tracking echocardiography was performed and left ventricular global longitudinal strain (GLS) and global longitudinal systolic strain rate were obtained. These measurements were repeated on the 10th day. RESULTS: NIHSS score improved, but infarct volume increased (p = 0.011 and 0.065, respectively) from admission to day 10. Ejection fraction was 53.2% and 55.8%, respectively, at admission and day 10 (p = 0.482), while GLS improved from -16.41% to -18.76% (p = 0.003). CONCLUSIONS: GLS and global longitudinal systolic strain rate showed significant improvement together with NIHSS score. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:305-311, 2016. PMID- 26888735 TI - Road safety in an aging population: risk factors, assessment, interventions, and future directions. AB - With the number of older drivers projected to increase by up to 70% over the next 20 years, preventing injury resulting from crashes involving older drivers is a significant concern for both policy-makers and clinicians. While the total number of fatal crashes per annum has steadily decreased since 2005 in Australia, the rate of fatalities has demonstrated an upward trend since 2010 in drivers aged 65 years and above (8.5 per 100,000), such that it is now on par with the fatality rate in drivers aged 17-25 years (8.0 per 100,000) (Austroads, 2015). Similar statistics are reported for the United States (NHTSA, 2012), implying there is a need for better identification of those older drivers who are unsafe and implementation of strategies that can enhance mobility while maximizing road safety. PMID- 26888736 TI - What is the potential for improving care and lowering cost for persons with dementia? AB - The increasing prevalence of dementia with population aging has heightened interest in understanding patterns of utilization and health expenditures in persons with dementia (PWD) among policy officials, practicing physicians, and health system. While a substantial part of this interest is concerned with the high costs of care for people diagnosed with dementia (Kelley et al., 2015), less attention has been focused on the costs and consequences of missed or delayed diagnosis in those who screen positive for dementia. The article on "Healthcare resource utilization and cost in dementia: are there differences between patients screened positive for dementia with and those without a formal diagnosis of dementia in primary care in Germany?" by Michalowsky and colleagues (Michalowsky et al., 2015) in this issue makes a particularly important contribution in this regard. PMID- 26888737 TI - Emotion regulation and psychopathological symptoms of Chinese school-age children: A person-centred and multi-informant approach. AB - Emotion regulation (ER) is a critical component of children's development. Many previous studies have utilised a single-assessment method to reflect child ER, which might result in losing important information regarding the unique contribution of each informant. With a person-centred approach and multi informant reports (mother, teacher and child), the current study examined 196 children's (age M = 9.21, SD = 1.10, range = 7-11 years; 51% girls) ER patterns and their associations with psychopathological symptoms in a Chinese sample. A model-based clustering procedure resulted in 3 ER groups: the poor family ER group (n = 36), poor school ER group (n = 120), and overall good ER group (n = 40). Significant differences were found among ER clusters on teacher-reported child psychopathological symptoms compared on the levels of withdrawn depression, somatic complain, thought problems and attention problems. No significant differences were found on the mother-reported psychopathological symptoms. Compared with children in the poor school or poor family ER clusters, children in the overall good ER group demonstrated fewer psychopathological symptoms at school. Our results confirmed the advantage of adopting multi-informant assessments to fully capture children's emotional profiles and linked these profiles with children's emotional and behavioural functioning at school. PMID- 26888738 TI - Association of XPF Levels and Genetic Polymorphism with Susceptibility to Ischemic Stroke. AB - The xeroderma pigmentosum group F (XPF) gene participates in the pathophysiological process of ischemic stroke, and XPF polymorphisms might be associated with ischemic stroke susceptibility. This study aimed to investigate XPF messenger RNA (mRNA) levels in peripheral blood mononuclear cells and protein levels in plasma and to analyze the 30028T/C polymorphism (rs1799801) in ischemic stroke patients and controls. Levels of both mRNA and protein in ischemic stroke patients were significantly lower than in controls (P < 0.05). The C allele of the 30028T/C polymorphism significantly increased the risk of ischemic stroke (OR = 1.512, 95 % CI = 1.219-1.875). The CT and CC/CT genotypes of 30028T/C were observed significantly more frequently in ischemic stroke patients than in controls (CT: OR = 1.916, 95 % CI = 1.446-2.539; CC/CT: OR = 1.877, 95 % CI = 1.427-2.468). Similar results were obtained after adjusting for age, gender, and smoking status. Additionally, XPF plasma protein levels were significantly decreased in the CC/CT genotype compared with the TT genotype (P = 0.025). These data indicate that XPF might play an important role in the pathophysiological process of ischemic stroke, and the 30028T/C polymorphism might be associated with ischemic stroke susceptibility in a Chinese Han population. PMID- 26888739 TI - Autoantigen-targeting microRNAs in Sjogren's syndrome. AB - MicroRNAs are short endogenous non-coding RNAs that regulate gene expression in various physiological and pathological conditions. To characterize autoantigen targeting microRNAs in Sjogren's syndrome (SS), a systematic study was carried out, in which a candidate microRNA set was first identified by bioinformatics analysis and literature search. Then, their gene silencing activities were evaluated with fusion reporter gene and endogenous targets, leading to the identification of three microRNAs: TRIM21-targeting miR-1207-5p, TRIM21-targeting miR-4695-3p, and La autoantigen-targeting miR-299-5p. Compared to healthy controls, downregulation of miR-1207-5p and miR-4695-3p expression was further revealed in the minor salivary glands of primary SS (pSS) patients. This, on the one hand, characterized two autoantigen-targeting microRNAs in Sjogren's syndrome and, on the other hand, suggested that downregulation of miR-1207-5p and miR-4695 3p expression may lead to increased TRIM21 levels in the minor salivary glands, which contributes to the development of Sjogren's syndrome. PMID- 26888740 TI - Tolerance of exercise-induced pain at a fixed rating of perceived exertion predicts time trial cycling performance. AB - To compare the predictive capacity of experimental pain and exercised-induced pain (EIP) on exercise performance. Thirty-two recreationally active male (n = 23) and female (n = 9) participants were recruited. Participants completed measures of pain tolerance by cold pressor test (CPT), pain pressure threshold via algometry (PPT), and EIP tolerance using an RPE clamp trial. A VO2max test provided traditional predictors of performance [VO2max , gas-exchange threshold (GET), peak power output (PPO)]. Finally, participants completed a 16.1-km cycling time trial (TT). No correlation was found between experimental pain measures (CPT, PPT) and TT performance. However, there was a significant correlation between EIP tolerance and TT performance (R = -0.83, P < 0.01). Regression analysis for pain and physiological predictor variables (mean pain in CPT, PPT, EIP tolerance, VO2max , PPO, GET) revealed that a significant model (P < 0.01) emerged when only PPO (Adjusted R2 = 0.739) and EIP tolerance (DeltaR2 = 0.075) were used to predict TT performance. These findings suggest that EIP tolerance is an important factor in endurance performance. However, PPT and CPT have limited ability to assess this relationship, and so their use in EIP research should be treated with caution. PMID- 26888741 TI - Hog1p activation by marasmic acid through inhibition of the histidine kinase Sln1p. AB - BACKGROUND: The histidine kinase (HK) MoHik1p within the high-osmolarity glycerol (HOG) pathway is known to be the target of the fungicide fludioxonil. Treatment of the fungus with fludioxonil causes an uncontrolled hyperactivation of the pathway and cell death. In this study, we used a target-based in vivo test system with mutant strains of the rice blast fungus Magnaporthe oryzae to search for new fungicidal compounds having various target locations within the HOG pathway. Mutants with inactivated HOG signalling are resistant to fungicides having the target located in the HOG pathway. RESULTS: The HK MoSln1p was identified as being involved in the new antifungal mode of action of marasmic acid, as single inactivation of the genes MoSLN1, MoSSK1, MoSSK2, MoPBS2 and MoHOG1 resulted in mutant strains resistant against the sesquiterpenoid, whereas the wild-type strain and the DeltaMohik1 mutant were susceptible. Western blot analysis of phosphorylated MoHog1p confirmed the hypothesis that marasmic acid interferes with the HOG pathway, as a strong phosphorylation of MoHog1p was detectable after sesquiterpenoid treatment in the wild-type strain but not in the DeltaMosln1 mutant. CONCLUSION: This study provides evidence for marasmic acid activating the HOG pathway via the HK MoSln1p, and we propose that the sesquiterpenoid has a new mode of action in M. oryzae that differs from that of known HOG inhibitors, e.g. fludioxonil. (c) 2016 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID- 26888742 TI - Lung transplantation for diffuse panbronchiolitis: 5 cases from a single centre. AB - Diffuse panbronchiolitis is a rare complex genetic disease predominantly affecting East Asians, and is characterized by chronic inflammation of the respiratory bronchioles and sinobronchial infection. Although long-term macrolide therapy has been shown to significantly improve the survival in patients with diffuse panbronchiolitis, some patients continue to deteriorate, eventually requiring lung transplantation. However, lung transplantation for diffuse panbronchiolitis has rarely been reported and the outcome in these patients remains unknown. We describe our experience of lung transplantation for diffuse panbronchiolitis. A total of 5 patients received long-term macrolide therapy and had airway colonization by Pseudomonas aeruginosa preoperatively. Three patients had undergone sinus surgery for chronic rhinosinusitis before the transplantation. Bilateral cadaveric lung transplantation was performed in 4 patients, and living-donor lung transplantation in 1. After the lung transplantation, 1 patient developed an A3 acute rejection episode; however, none of the recipients developed severe pneumonia or any fatal infections. One recipient developed chronic lung allograft dysfunction 3 years after the transplantation; however, none developed recurrence of diffuse panbronchiolitis. All of the 5 patients were still surviving after a median follow-up period of 4.9 years (3.7-12.3 years). Lung transplantation is a viable option for the treatment of progressive diffuse panbronchiolitis resistant to long-term macrolide therapy. PMID- 26888743 TI - Long-term total cardiac support in a Fontan-type circulation with HeartMate II left ventricular assist device. AB - Interest in utilizing long-term mechanical circulatory support for Fontan-type circulation has been high. Unfortunately, so far such attempts have not been successful. Herein, we are presenting the first case of an individual with biventricular heart failure and Fontan-type circulation on long-term mechanical circulatory support with a continuous-flow left ventricular assist device. PMID- 26888744 TI - Is off-pump technique a safer procedure for coronary revascularization? A propensity score analysis of 20 years of experience. AB - OBJECTIVES: We aim to describe our experience in coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass by comparing intraoperative and postoperative outcomes. METHODS: From January 1993 to June 2013, 3097 patients underwent consecutive emergency and scheduled CABG surgery. A total of 1770 patients underwent on-pump CABG (ONCABG) and 1327 off-pump CABG (OPCABG). A propensity score matching was performed to identify appropriate matched-pair patients; univariable and multivariable logistic regression analyses were performed to assess significant predictors of hospital and 30-day morbidity and mortality composite end-points. Morbidity composite end-point was defined as any renal, pulmonary, cardiovascular and neurological complication that occurred during hospital stay. We collected all-cause mortality data during the study period. RESULTS: We identified 1004 patients in each group. There were no significant differences in thirty day mortality, 2.8 vs 3.8%, in OPCABG and ONCABG, respectively (P = 0.21). Cardiovascular, neurological, respiratory and renal complications were more frequent in the ONCABG group: 13.9 vs 8.7% (P < 0.001), 3.9 vs 2.2% (P = 0.03), 13.5 vs 7.5% (P < 0.001), 7.1 vs 5.3% (P = 0.095), respectively. The long-term all-cause mortality rate was 12.3 vs 12.9% in the OPCABG versus ONCABG group (P = 0.42), respectively. In both uni- and multivariable analysis preoperative renal failure, chronic obstructive pulmonary disease and ONCABG were independent predictors of mortality and morbidity composite end-points. CONCLUSIONS: OPCABG is associated with less postoperative morbimortality and shorter hospital and intensive care unit length of stay. ONCABG resulted as an independent predictor of morbidity and mortality composite end-point. No statistically significant differences were observed in long-term all-cause mortality between groups. PMID- 26888745 TI - Extraction and coordination studies of a carbonyl-phosphine oxide scorpionate ligand with uranyl and lanthanide(III) nitrates: structural, spectroscopic and DFT characterization of the complexes. AB - Hybrid scorpionate ligand (OPPh2)2CHCH2C(O)Me (L) was synthesized and characterized by spectroscopic methods and X-ray diffraction. The selected coordination chemistry of L with UO2(NO3)2 and Ln(NO3)3 (Ln = La, Nd, Lu) has been evaluated. The isolated mono- and binuclear complexes, namely, [UO2(NO3)2L] (1), [{UO2(NO3)L}2(MU2-O2)].EtOH (2), [La(NO3)3L2].2.33MeCN (3), [Nd(NO3)3L2].3MeCN (4), [Nd(NO3)2L2]+.(NO3)-.EtOH (5) and [Lu(NO3)3L2] (6) have been characterized by IR spectroscopy and elemental analysis. Single-crystal X ray structures have been determined for complexes 1-5. Intramolecular intraligand pi-stacking interactions between two phenyl fragments of the coordinated ligand(s) were observed in all complexes 1-5. The pi-stacking interaction energy was estimated from Bader's AIM theory calculations performed at the DFT level. Solution properties have been examined using IR and multinuclear ((1)H, (13)C, and (31)P) NMR spectroscopy in CD3CN and CDCl3. Coordination modes of L vary with the coordination polyhedron of the metal and solvent nature showing many coordination modes: P(O),P(O), P(O),P(O),C(O), P(O),C(O), and P(O). Preliminary extraction studies of U(VI) and Ln(III) (Ln = La, Nd, Ho, Yb) from 3.75 M HNO3 into CHCl3 show that scorpionate L extracts f-block elements (especially uranium) better than its unmodified prototype (OPPh2)2CH2. PMID- 26888747 TI - Three Authors Reply. PMID- 26888748 TI - Prediction and Prevention of Autoimmune Disease in the 21st Century: A Review and Preview. AB - Autoimmune diseases represent a family of at least 80 illnesses that share a common pathogenesis: an immune-mediated attack on the body's own organs. Collectively, autoimmune diseases affect some 20 million Americans, predominantly women. Many of these diseases are increasing in frequency in industrialized countries. Treatment of autoimmune diseases improved greatly during the second half of the 20th century but has been hampered because the diseases often progress before a clinical diagnosis is possible. Research in the 21st century is focusing on prospective prediction using the tools of systems biology. PMID- 26888749 TI - Re: "Estimating Causal Associations of Fine Particles With Daily Deaths in Boston". PMID- 26888750 TI - Editorial: In Celebration of the Centennial of the Johns Hopkins Bloomberg School of Public Health. PMID- 26888751 TI - Cultivating Hygiene as a Science: The Welch-Rose Report's Influence at Johns Hopkins and Beyond. AB - In 1915, William Henry Welch and Wickliffe Rose submitted a report to the Rockefeller Foundation that became the template for public health professional education in the United States and abroad. Based on the Welch-Rose Report's recommendations, the Foundation awarded a grant to Johns Hopkins University in 1916 to establish the first independent graduate school of public health, with Welch serving as the founding dean. The Welch-Rose Report and, by extension, the Johns Hopkins School of Hygiene and Public Health established and transmitted a new model of scientific training that wove the laboratory mindset together with the methods of public health administration and epidemiologic fieldwork. During the School's first quarter-century, faculty and alumni were remarkably active in frontline public health problem-solving, as well as launching public health agencies and schools of all types and sizes. The most lasting contribution of the Welch-Rose Report and the Johns Hopkins School of Hygiene and Public Health, now the Johns Hopkins Bloomberg School of Public Health, has been to "cultivate the science of hygiene" to bring about exponential growth in the evidence base for public health. The schools that have adopted the Johns Hopkins model of public health education worldwide have produced professionals who have worked to achieve wide-ranging reforms dedicated to preserving life, protecting health, and preventing injury across populations and continents. PMID- 26888752 TI - Re: "Estimating Causal Associations of Fine Particles With Daily Deaths in Boston". PMID- 26888746 TI - Phosphatidylinositol 3-phosphates-at the interface between cell signalling and membrane traffic. AB - Phosphoinositides (PIs) form a minor class of phospholipids with crucial functions in cell physiology, ranging from cell signalling and motility to a role as signposts of compartmental membrane identity. Phosphatidylinositol 3 phosphates are present at the plasma membrane and within the endolysosomal system, where they serve as key regulators of both cell signalling and of intracellular membrane traffic. Here, we provide an overview of the metabolic pathways that regulate cellular synthesis of PI 3-phosphates at distinct intracellular sites and discuss the mechanisms by which these lipids regulate cell signalling and membrane traffic. Finally, we provide a framework for how PI 3-phosphate metabolism is integrated into the cellular network. PMID- 26888753 TI - Hierarchical Distributed-Lag Models: Exploring Varying Geographic Scale and Magnitude in Associations Between the Built Environment and Health. AB - It is well known that associations between features of the built environment and health depend on the geographic scale used to construct environmental attributes. In the built environment literature, it has long been argued that geographic scales may vary across study locations. However, this hypothesized variation has not been systematically examined due to a lack of available statistical methods. We propose a hierarchical distributed-lag model (HDLM) for estimating the underlying overall shape of food environment-health associations as a function of distance from locations of interest. This method enables indirect assessment of relevant geographic scales and captures area-level heterogeneity in the magnitudes of associations, along with relevant distances within areas. The proposed model was used to systematically examine area-level variation in the association between availability of convenience stores around schools and children's weights. For this case study, body mass index (weight kg)/height (m)2) z scores (BMIz) for 7th grade children collected via California's 2001-2009 FitnessGram testing program were linked to a commercial database that contained locations of food outlets statewide. Findings suggested that convenience store availability may influence BMIz only in some places and at varying distances from schools. Future research should examine localized environmental or policy differences that may explain the heterogeneity in convenience store-BMIz associations. PMID- 26888754 TI - Phantom model and scoring system to assess ability in ultrasound-guided chest drain positioning. AB - BACKGROUND: Chest tube positioning is an invasive procedure associated with potentially serious injuries. In the last few years, we have been running a project directed at developing a practical simulator of a surgical procedure taught on our medical training program. The phantom model reconstructs the pleural anatomy, visible by lung ultrasound, used for the assessed performance of the Seldinger technique. The aim of the present study was to investigate the validity of this simulation technology for assessing residents in anesthesia and intensive care medicine; specifically, their skill in positioning a US-guided chest tube drain was tested using the simulator device. The second aim of the paper was to evaluate the learning curve of our residents over their 5-year study course and validate the phantom scoring system. METHODS: This was a prospective, single-blinded observational study. Participants were recruited from residents in anesthesia and intensive care medicine and divided into two groups: 'Novice' and 'Expert,' based on the course year attended (years 1, 2, and 3 vs. years 4 and 5, respectively). We asked them to position a chest tube drain in a phantom model, guided by ultrasound, to drain a simulated pleural effusion. Each subject performed two tests that simulated pleural effusions of 4 and 2 cm, respectively. Every step of the maneuver was constantly monitored and the performance scored by the investigators. We then performed a Spearman correlation analysis to evaluate the effect of experience level on the performance of the two groups of residents. RESULTS: Thirty-one residents were included in this study: 20 in the Novice group and 11 in the Expert group. The mean performance rating score was 0.75 +/- 4.38 for the Novice Group and 5.91 +/- 3.75 for the Expert group (p = 0.0026). The Spearman correlation analysis examining the relationship between year of residency and performance rating score confirmed a positive correlation (r = 0.58, p = 0.0006). Post-test trend analysis revealed a statistically significant linear trend for skill growth across time, i.e., course year (p = 0.0022). CONCLUSIONS: Our simulated procedure using a phantom model of lung anatomy can accurately and reliably be used to assess the skill levels of operators in their ability to drain pleural effusion. PMID- 26888756 TI - Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production. AB - Loss of function of the insulin receptor (INSR) in humans produces severe insulin resistance. Unlike "common" insulin resistance, this is associated with elevated plasma levels of the insulin-sensitising, adipose-derived protein adiponectin. The underlying mechanism for this paradox is unclear, and it is at odds with the acute stimulation of adiponectin secretion reported on insulin treatment of cultured adipocytes. Given recent evidence for ligand-independent actions of the INSR, we used a lentiviral system to knock down Insr or its substrates Irs1 and Irs2 conditionally in 3T3-L1 murine preadipocytes/adipocytes to assess whether acute loss of their expression has different consequences to withdrawal of insulin. Efficient knockdown of either Insr or Irs1/2 was achieved by conditional shRNA expression, severely attenuating insulin-stimulated AKT phosphorylation and glucose uptake. Dual knockdown of Irs1 and Irs2 but not Insr in preadipocytes impaired differentiation to adipocytes. Acute knockdown of Insr or both Irs1 and Irs2 in adipocytes increased Adipoq mRNA expression but reduced adiponectin secretion, assessed by immunoassay. Knockdown sustained for 14 days also reduced immunoassay-detected adiponectin secretion, and moreover induced delipidation of the cells. These findings argue against a distinct effect of Insr deficiency to promote adiponectin secretion as the explanation for paradoxical insulin receptoropathy-related hyperadiponectinaemia. PMID- 26888758 TI - Erratum. PMID- 26888755 TI - Expansins: roles in plant growth and potential applications in crop improvement. AB - KEY MESSAGE: Results from various expansin related studies have demonstrated that expansins present an opportunity to improve various crops in many different aspects ranging from yield and fruit ripening to improved stress tolerance. The recent advances in expansin studies were reviewed. Besides producing the strength that is needed by the plants, cell walls define cell shape, cell size and cell function. Expansins are cell wall proteins which consist of four sub families; alpha-expansin, beta-expansin, expansin-like A and expansin-like B. These proteins mediate cell wall loosening and they are present in all plants and in some microbial organisms and other organisms like snails. Decades after their initial discovery in cucumber, it is now clear that these small proteins have diverse biological roles in plants. Through their ability to enable the local sliding of wall polymers by reducing adhesion between adjacent wall polysaccharides and the part they play in cell wall remodeling after cytokinesis, it is now clear that expansins are required in almost all plant physiological development aspects from germination to fruiting. This is shown by the various reports from different studies using various molecular biology approaches such as gene achieve these many roles through their non-enzymatic wall loosening ability. This paper reviews and summarizes some of the reported functions of expansins and outlines the potential uses of expansins in crop improvement programs. PMID- 26888757 TI - Low Vision Rehabilitation, Age-Related Vision Loss, and Risk: A Critical Interpretive Synthesis. AB - PURPOSE: Given the centrality of risk in geriatric rehabilitation, it is critically important to attend to how conceptualizations of risk shape research, policies, and rehabilitation practices. This paper presents a critical interpretive synthesis (CIS) of literature addressing risk and low vision rehabilitation for older adults with age-related vision loss (ARVL) to identify key guiding assumptions regarding risk and discuss implications for what gets attended to, and not attended to, within research and rehabilitation. DESIGN AND METHODS: This CIS combined guidelines proposed by Dixon-Woods and colleagues (2006-Conducting a critical interpretive synthesis of the literature on access to healthcare by vulnerable groups. BMC Medical Research Methodology, 6, 35) and Alvesson and Sandberg (2011-Generating research questions through problematization. Academy of Management Review, 36, 247-271; 2013-Constructing research questions: Doing interesting research. London: Sage). The iterative review process involved 3 steps: literature search and selection, data extraction, and syntheses to identify boundary assumptions. The dataset included 83 research and practice description articles. RESULTS: Older adults with ARVL were constructed as "at risk" for various adverse outcomes, particularly dependency and self-harm, and as posing risks to others. An epidemiological approach to risk based in assumptions aligned with a technico-scientific perspective was dominant, with risk conceptualized as an embodied, individual level phenomenon that is to be determined and managed through objective screening and expert monitoring. IMPLICATIONS: Key concerns include a lack of: attention to the tensions created when rehabilitation research and practice attempt to promote independence while simultaneously reducing risk, incorporation of aging adults' perspectives on risk, and analysis of environmental factors that shape risks. Research that starts by valuing older adults' experiences and attends to context can inform rehabilitation practices that support health-promoting, risk-taking, and facilitate collaborative approaches to risk management. PMID- 26888760 TI - Erratum to: Novel Report of Phosphoserine Phosphatase Deficiency in an Adult with Myeloneuropathy and Limb Contractures. PMID- 26888759 TI - The extended Infant Feeding, Activity and Nutrition Trial (InFANT Extend) Program: a cluster-randomized controlled trial of an early intervention to prevent childhood obesity. AB - BACKGROUND: Understanding how we can prevent childhood obesity in scalable and sustainable ways is imperative. Early RCT interventions focused on the first two years of life have shown promise however, differences in Body Mass Index between intervention and control groups diminish once the interventions cease. Innovative and cost-effective strategies seeking to continue to support parents to engender appropriate energy balance behaviours in young children need to be explored. METHODS/DESIGN: The Infant Feeding Activity and Nutrition Trial (InFANT) Extend Program builds on the early outcomes of the Melbourne InFANT Program. This cluster randomized controlled trial will test the efficacy of an extended (33 versus 15 month) and enhanced (use of web-based materials, and Facebook(r) engagement), version of the original Melbourne InFANT Program intervention in a new cohort. Outcomes at 36 months of age will be compared against the control group. DISCUSSION: This trial will provide important information regarding capacity and opportunities to maximize early childhood intervention effectiveness over the first three years of life. This study continues to build the evidence base regarding the design of cost-effective, scalable interventions to promote protective energy balance behaviors in early childhood, and in turn, promote improved child weight and health across the life course. TRIAL REGISTRATION: ACTRN12611000386932. Registered 13 April 2011. PMID- 26888761 TI - Preprocessing strategy influences graph-based exploration of altered functional networks in major depression. AB - Resting-state fMRI studies have gained widespread use in exploratory studies of neuropsychiatric disorders. Graph metrics derived from whole brain functional connectivity studies have been used to reveal disease-related variations in many neuropsychiatric disorders including major depression (MDD). These techniques show promise in developing diagnostics for these often difficult to identify disorders. However, the analysis of resting-state datasets is increasingly beset by a myriad of approaches and methods, each with underlying assumptions. Choosing the most appropriate preprocessing parameters a priori is difficult. Nevertheless, the specific methodological choice influences graph-theoretical network topologies as well as regional metrics. The aim of this study was to systematically compare different preprocessing strategies by evaluating their influence on group differences between healthy participants (HC) and depressive patients. We thus investigated the effects of common preprocessing variants, including global mean-signal regression (GMR), temporal filtering, detrending, and network sparsity on group differences between brain networks of HC and MDD patients measured by global and nodal graph theoretical metrics. Occurrence of group differences in global metrics was absent in the majority of tested preprocessing variants, but in local graph metrics it is sparse, variable, and highly dependent on the combination of preprocessing variant and sparsity threshold. Sparsity thresholds between 16 and 22% were shown to have the greatest potential to reveal differences between HC and MDD patients in global and local network metrics. Our study offers an overview of consequences of methodological decisions and which neurobiological characteristics of MDD they implicate, adding further caution to this rapidly growing field. PMID- 26888762 TI - Multiparametric MRI of the anterior prostate gland: clinical-radiological histopathological correlation. AB - Anterior prostate cancer (APC) is defined as a tumour in which more than half of malignant tissue is located anterior to the urethra. APCs are increasingly recognized as clinically important, particularly in patients undergoing active surveillance and for patients with negative non-targeted systematic transrectal ultrasound (TRUS)-guided biopsies but with persistent clinical suspicion of cancer. Multiparametric (mp) MRI has a crucial role for the diagnosis of anterior tumours, eventual histological sampling of suspicious lesions using image-guided targeted biopsy techniques, and potentially, to improve local staging of disease. mpMRI is accurate for the detection of APC and for differentiation of tumour from other anterior prostatic structures including benign prostatic hyperplasia (BPH) and the anterior fibromuscular stroma (AFMS). Characterization and reporting of APC should rely on the recently revised Prostate Imaging and Data Reporting System (PI-RADS) version 2.0 document. T2-weighted (T2W) imaging is emphasized as the determining sequence for assessment of the anterior prostate and specific features for APC on T2W imaging include: ill-defined/spiculated margin, lenticular shape, anterior/inferior location, and growth pattern (invasion of urethra or AFMS and crossing midline). Functional imaging, mainly with diffusion weighted imaging, is also contributory and improves the sensitivity for detection of APC compared to T2W imaging alone. APCs commonly show positive surgical margins after radical prostatectomy and staging of disease extent using conventional clinical parameters is limited. mpMRI may have a future role to improve local staging of APC. This review illustrates the importance of mpMRI in APC using a clinical-radiological-histopathological approach. PMID- 26888764 TI - The recognition of abnormal fetal heart rate patterns is improved by knowledge of fetal pH. PMID- 26888763 TI - The negative effect of starvation and the positive effect of mild thermal stress on thermal tolerance of the red flour beetle, Tribolium castaneum. AB - The thermal tolerance of a terrestrial insect species can vary as a result of differences in population origin, developmental stage, age, and sex, as well as via phenotypic plasticity induced in response to changes in the abiotic environment. Here, we studied the effects of both starvation and mild cold and heat shocks on the thermal tolerance of the red flour beetle, Tribolium castaneum. Starvation led to impaired cold tolerance, measured as chill coma recovery time, and this effect, which was stronger in males than females, persisted for longer than 2 days but less than 7 days. Heat tolerance, measured as heat knockdown time, was not affected by starvation. Our results highlight the difficulty faced by insects when encountering multiple stressors simultaneously and indicate physiological trade-offs. Both mild cold and heat shocks led to improved heat tolerance in both sexes. It could be that both mild shocks lead to the expression of heat shock proteins, enhancing heat tolerance in the short run. Cold tolerance was not affected by previous mild cold shock, suggesting that such a cold shock, as a single event, causes little stress and hence elicits only weak physiological reaction. However, previous mild heat stress led to improved cold tolerance but only in males. Our results point to both hardening and cross tolerance between cold and heat shocks. PMID- 26888765 TI - Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine. AB - BACKGROUND: Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. METHODS AND RESULTS: From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including lifestyle factors were linked to event data from validated national registers. The risk prediction model was developed by using a 2-stage approach. First, a nonparametric, data-driven approach was used to identify potentially informative risk factors and interactions (random forest and survival tree analysis). Second, based on results from the first step, Poisson regression analysis was used to derive the final model. The final CVD prediction model was externally validated in a different population of 2119 patients with type 1 diabetes mellitus. During a median follow up of 6.8 years (interquartile range, 2.9-10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent for a 5-year CVD event with a C-statistic of 0.826 (95% confidence interval, 0.807-0.845) in the derivation data and a C-statistic of 0.803 (95% confidence interval, 0.767-0.839) in the validation data. The Hosmer-Lemeshow test showed good calibration (P>0.05) in both cohorts. CONCLUSIONS: This high performing CVD risk model allows for the implementation of decision rules in a clinical setting. PMID- 26888766 TI - The Prediction of Atherosclerotic Cardiovascular Disease in Type 1 Diabetes Mellitus: Do We Just Stop Here? PMID- 26888768 TI - Lactobacillus acidophilus Restores Functionality in Uremic Macrophages: Plausible or Lacking Evidence? PMID- 26888770 TI - Gaining an accurate reflection of the reality of palliative care through the use of free-text feedback in questionnaires: the AFTER study. AB - BACKGROUND: In healthcare, many service evaluation questionnaires use free-text boxes without formal mechanisms for analysis. Patients and carers spend time documenting concerns that are often ignored or managed locally in an ad hoc manner. Currently, palliative care experiences of patients and carers in Wales are measured using a service evaluation questionnaire, comprising both closed and open-ended questions. Previous research, exploring free-text responses from this questionnaire, suggests that questionnaire refinement should accommodate service users' expressed priorities and concerns, and highlights the need to incorporate free-text data analysis strategies during study design. METHODS: Results from a previous analysis of 596 free-text responses provided the basis for an expert consensus day, where the current service evaluation questionnaire was refined. The refined version was tested during cognitive interviews with patients (n=10) and carers (n=7) receiving palliative care from 1 of 2 UK hospices. Data were analysed thematically. RESULTS: Interviews highlighted minor areas for change within the questionnaire and provided broader insight into patients' experiences of palliative care services. Patients and carers place an emphasis on simplifying language, decreasing the numeric response range and reducing written instructions; relying instead on visual cues, including formatting and layout. Findings highlighted the importance patients attached to providing meaningful free-text contributions. CONCLUSIONS: Questionnaire refinement should use the patient perspective to effectively facilitate respondent understanding, pertinence and usability. The importance of employing data analysis strategies during questionnaire design may reduce research waste, thus enabling a better interrogation of service provision. PMID- 26888771 TI - Charge-transfer interactions between TCNQ and silver clusters Ag20 and Ag13. AB - Interactions between tetracyanoquinodimethane (TCNQ) and two typical silver clusters Ag13 and Ag20 are studied by first-principles DFT calculations. Charge transfer (CT) from silver clusters to TCNQ molecules initiates the Ag-N bond formation at selective sites resulting in the formation of different isomers of Ag13-TCNQ and Ag20-TCNQ complexes. We show here a comprehensive spectroscopic analysis for the two CT complexes on the basis of Raman and infrared activities. Furthermore, frontier molecular orbital (FMO) and natural bond orbital (NBO) analysis of the complexes provides a vivid illustration of electron cloud overlap and interactions. The behavior of TCNQ adsorbed on the tetrahedral Ag20 cluster was even found in good agreement with the experimental measurement of TCNQ molecules on a single-crystal Ag(111) surface. This study not only endeavors to clarify the charge-transfer interactions of TCNQ with silver, but also presents a finding of enhanced charge transfer between Ag13 and TCNQ indicating potential for candidate building blocks of granular materials. PMID- 26888772 TI - Health Education England threatens to cut trusts' funding for training if they don't impose junior doctor contract. PMID- 26888767 TI - Factors Associated with the Success of In Vitro Fertilization in Women with Inflammatory Bowel Disease. AB - BACKGROUND: It is unknown whether certain factors are associated with the success of in vitro fertilization (IVF) in women with inflammatory bowel disease (IBD). AIM: This study assessed whether certain characteristics are associated with greater success of live birth following IVF. METHODS: In a cohort study of 8684 women with IBD seen at two tertiary care centers, we identified 121 women with IBD who underwent IVF. We assessed the effect of numerous factors on likelihood of achieving live birth after IVF. RESULTS: Seventy-one patients with ulcerative colitis (UC) and 49 patients with Crohn's disease (CD) were analyzed. Patients with UC who achieved a live birth were younger (p = 0.03), had a shorter duration of disease (p = 0.01), and were more likely to be in remission (p = 0.03) versus those who did not achieve live birth. Patients with CD who achieved live birth were younger (p < 0.001), had lower body mass index (BMI) (p = 0.02), and had lower cycle day 3 follicle-stimulating hormone levels (p = 0.02). There was no difference in likelihood of achieving live birth among patients in remission and those with mild or unknown disease status (p = 0.69), though most CD patients (79.5 %) were in remission. Prior surgery was not associated with live birth in patients with UC (p = 0.31) or CD (p = 0.62). CONCLUSIONS: As in the general infertility population, younger patients and those with lower BMI were more likely to achieve live birth. History of surgery was not associated with live birth among IBD patients. This is important information for practitioners counseling IBD patients. PMID- 26888773 TI - Voting for change in Myanmar. PMID- 26888769 TI - Management of Eosinophilic Esophagitis During Pregnancy. AB - There are currently limited data on the management of eosinophilic esophagitis (EoE) during pregnancy. At our center, however, we have followed several pregnant women with EoE and others have asked pertinent questions in pre-pregnancy counseling. The relatively young age of patients with EoE implies that many practitioners will also encounter patients with these questions. In this review, we use four cases to prompt a discussion about concerns focused on the safety of steroids and diet therapy during pregnancy and breast-feeding, potential nutritional risks with dietary elimination, how to optimize therapy, and whether endoscopic evaluation for monitoring of disease activity is safe during pregnancy and breast-feeding. An additional concern is whether the disease could progress during pregnancy and breast-feeding if no therapies are used. Although there are no studies specifically examining pregnant EoE patients, we have reviewed the literature relevant to this population as informed by the treatment of inflammatory bowel disease patients during pregnancy, where these issues have been studied in more depth. Providers who care for EoE patients who could become pregnant should familiarize themselves with these issues. PMID- 26888774 TI - Asymmetric optical properties of photocatalytically deposited plasmonic silver nanoparticles. AB - Ag nanoparticles deposited and grown photocatalytically for a sufficient period of time on a TiO2 thin film scatter blue light and reflect reddish light when the particles are irradiated directly (i.e. front incidence). On the other hand, they scatter reddish light and reflect blue light when the particles are irradiated through the TiO2 film (i.e. back incidence). The asymmetric optical behaviour is attributed to the asymmetric plasmon resonance, for which a sufficient height and a sufficient width at the top and the bottom of the Ag nanoparticles are important. PMID- 26888775 TI - Differential Response of Human Hepatocyte Chromatin to HDAC Inhibitors as a Function of Microenvironmental Glucose Level. AB - Diabetes is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion. Recent observations suggest that the complexity of the disease cannot be entirely accounted for genetic predisposition and a compelling argument for an epigenetic component is rapidly emerging. The use of histone deacetylase inhibitor (HDACi) in clinical setting is an emerging area of investigation. In this study, we have aimed to understand and compare the response of hepatocyte chromatin to valproic acid (VPA) and trichostatin A (TSA) treatments under normoglycemic or hyperglycemic conditions to expand our knowledge about the consequences of HDACi treatment in a diabetes cell model. Under normoglycemic conditions, these treatments promoted chromatin remodeling, as assessed by image analysis and H3K9ac and H3K9me2 abundance. Simultaneously, H3K9ac marks shifted to the nuclear periphery accompanied by HP1 dissociation from the heterochromatin and a G1 cell cycle arrest. More striking changes in the cell cycle progression and mitotic ratios required drastic treatment. Under hyperglycemic conditions, high glucose per se promoted chromatin changes similar to those promoted by VPA and TSA. Nonetheless, these results were not intensified in cells treated with HDACis under hyperglycemic conditions. Despite the absence of morphological changes being promoted, HDACi treatment seems to confer a physiological meaning, ameliorating the cellular hyperglycemic state through reduction of glucose production. These observations allow us to conclude that the glucose level to which the hepatocytes are subjected affects how chromatin responds to HDACi and their action under high-glucose environment might not reflect on chromatin remodeling. J. Cell. Physiol. 231: 2257-2265, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26888776 TI - RNAi-mediated plant protection against aphids. AB - Aphids (Aphididae) are major agricultural pests that cause significant yield losses of crop plants each year by inflicting damage both through the direct effects of feeding and by vectoring harmful plant viruses. Expression of double stranded RNA (dsRNA) directed against suitable insect target genes in transgenic plants has been shown to give protection against pests through plant-mediated RNA interference (RNAi). Thus, as a potential alternative and effective strategy for insect pest management in agricultural practice, plant-mediated RNAi for aphid control has received close attention in recent years. In this review, the mechanism of RNAi in insects and the so far explored effective RNAi target genes in aphids, their potential applications in the development of transgenic plants for aphid control and the major challenges in this regard are reviewed, and the future prospects of using plant-mediated RNAi for aphid control are discussed. This review is intended to be a helpful insight into the generation of aphid resistant plants through plant-mediated RNAi strategy. (c) 2016 Society of Chemical Industry. PMID- 26888777 TI - Sympathomodulatory Effects of Antihypertensive Drug Treatment. AB - BACKGROUND: An activation of sympathetic neural influences to the heart and peripheral circulation has been shown to represent a hallmark of the essential hypertensive state, adrenergic neural factors participating together with other variables at the development and progression of the high blood pressure state as well as of the hypertension-related target organ damage. This represents the rationale for employing in hypertension treatment drugs which combine the blood pressure-lowering properties with the modulatory effects on the sympathetic neural function. METHODS AND RESULTS: Several studies published during the past 40 years have investigated the impact of antihypertensive drugs on the sympathetic target as assessed by indirect and direct approaches. In the present paper, the effects of different monotherapies or combination drug treatment used in hypertension to lower elevated blood pressure values on various adrenergic markers will be examined. This will be followed by a discussion of the (i) hemodynamic and nonhemodynamic consequences of employing antihypertensive drugs with sympathomodulatory or sympathoexcitatory properties and (ii) mechanisms potentially responsible for the adrenergic responses to a given antihypertensive drug. The final part of this review will address the questions still open related to the impact of antihypertensive drug treatment on sympathetic function. Two questions in particular will be examined, i.e., whether antihypertensive drugs with sympathomodulatory properties may be capable to fully restore a "normal" adrenergic drive and how far sympathetic activity should be reduced in hypertensive patients. CONCLUSION: Future investigations aimed at answering these questions will be needed in order to improve cardiovascular protection in treated hypertensive patients. PMID- 26888778 TI - Clinical Characteristics and Lifestyle Behaviors in a Population-Based Sample of Chinese and South Asian Immigrants With Hypertension. AB - BACKGROUND: Asian Americans are the fastest growing racial/ethnic group in the United States. Chinese Americans and their counterparts in Chinese countries have been shown to have an elevated risk of stroke compared to non-Hispanic Whites, while South Asian Americans and their counterparts in South Asian countries have an elevated risk of heart disease. Exactly how cardiovascular disease morbidity varies by Asian subgroup, however, is not well understood. The purpose of this analysis was to identify differences in clinical presentation and lifestyle behaviors between Chinese and South Asian American immigrants vs. non-Hispanic Whites in a representative sample of adults with self-report of physician diagnosed hypertension. METHODS: Data on adults with self-reported hypertension were obtained from the New York City Community Health Survey 2009-2013 (Chinese: n = 555; South Asian: n = 144; non-Hispanic White: n = 5,987). RESULTS: Compared to non-Hispanic Whites with hypertension, foreign-born Chinese adults with hypertension were of a much lower socioeconomic profile and less likely to have private health insurance, and foreign-born Chinese and South Asian adults with hypertension had lower body mass index (BMI) values (25.3, 26.0 vs. 28.7kg/m(2); P < 0.001). South Asians were younger than non-Hispanic Whites (mean age: 49.5 vs. 62.1 years; P < 0.001) and had poorer diet quality. BMI and diet quality results persisted in multivariable regression models. CONCLUSIONS: Findings from this study highlight important clinical distinctions in hypertensive Chinese and South Asian immigrant communities with respect to age and body size. Whether targeted and culturally appropriate approaches would reduce cardiovascular disease-related mortality in these groups needs further study. PMID- 26888779 TI - TB in healthcare workers in the UK: a cohort analysis 2009-2013. AB - OBJECTIVES: To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure. METHODS: Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth. RESULTS: 2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients. CONCLUSIONS: The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities. PMID- 26888780 TI - Increasing burden of community-acquired pneumonia leading to hospitalisation, 1998-2014. AB - BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of mortality and morbidity in many countries but few recent large-scale studies have examined trends in its incidence. METHODS: Incidence of CAP leading to hospitalisation in one UK region (Oxfordshire) was calculated over calendar time using routinely collected diagnostic codes, and modelled using piecewise-linear Poisson regression. Further models considered other related diagnoses, typical administrative outcomes, and blood and microbiology test results at admission to determine whether CAP trends could be explained by changes in case-mix, coding practices or admission procedures. RESULTS: CAP increased by 4.2%/year (95% CI 3.6 to 4.8) from 1998 to 2008, and subsequently much faster at 8.8%/year (95% CI 7.8 to 9.7) from 2009 to 2014. Pneumonia-related conditions also increased significantly over this period. Length of stay and 30-day mortality decreased slightly in later years, but the proportions with abnormal neutrophils, urea and C reactive protein (CRP) did not change (p>0.2). The proportion with severely abnormal CRP (>100 mg/L) decreased slightly in later years. Trends were similar in all age groups. Streptococcus pneumoniae was the most common causative organism found; however other organisms, particularly Enterobacteriaceae, increased in incidence over the study period (p<0.001). CONCLUSIONS: Hospitalisations for CAP have been increasing rapidly in Oxfordshire, particularly since 2008. There is little evidence that this is due only to changes in pneumonia coding, an ageing population or patients with substantially less severe disease being admitted more frequently. Healthcare planning to address potential further increases in admissions and consequent antibiotic prescribing should be a priority. PMID- 26888781 TI - Toll-like receptor 5 and 7 expression in adenoid cystic carcinoma of major salivary glands. AB - Adenoid cystic carcinoma (ACC) of the salivary glands has a poor long-term prognosis and high metastatic rate. Toll-like receptors (TLRs) have been related to tumour progression but have also tumour growth-inhibiting responses. To the best of our knowledge, they have not been studied previously in ACC. We studied the immunoexpression of TLR 5 and 7 in ACC of the major salivary glands. From a cohort of 54 patients with ACC of the major salivary glands treated at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland in 1974-2009, there were 34 primary tumours and six metastases available for immunohistochemical analysis. Immunohistochemical expression of TLR 5 and 7 were correlated to clinicopathological findings and patient survival. Both TLR 5 and 7 were expressed in ACCs and their metastases, mostly on the cell membranes. The expression was heterogeneous in individual tumours. TLR 5 was expressed less in male samples, and TLR 7 had lower expression in ACCs with solid growth pattern. No correlation with survival was found. In the normal salivary gland, the TLR 5 and 7 expression was mainly negative. Both TLR 5 and 7 are expressed in salivary adenoid cystic carcinoma on the cell membranes as well as in cytoplasm. PMID- 26888783 TI - Malnutrition in rectal cancer patients receiving preoperative chemoradiotherapy is common and associated with treatment tolerability and anastomotic leakage. AB - PURPOSE: This study assessed the incidence of malnutrition caused by preoperative chemoradiotherapy (CRT) in rectal cancer patients, which is seemingly underestimated; however, malnutrition affects treatment tolerability, postoperative complications, including anastomotic leakage (AL), and oncological outcomes. METHODS: Between January 2008 and December 2014, 54 consecutive patients with T3-4, N0-2, M0-1 resectable rectal cancer received CRT comprising 45 Gy radiotherapy and S-1 alone or with irinotecan for 5 weeks and then underwent curative surgery with diverting or permanent stomas 6-8 weeks after CRT. We assessed malnutrition after completion of CRT (5-6 weeks after CRT start date) and at surgery (11-14 weeks after CRT start date), defining weight loss as >=5 % of pre-CRT weight; this definition differs from commonly used criteria for adverse events. We evaluated the incidence of malnutrition associated with CRT and influence of malnutrition on treatment tolerability, AL, and disease-free survival (DFS). We also assessed the influence of CRT on the rate of postoperative complications by comparing the study group with 61 patients who had undergone excision with diverting or permanent stomas alone. RESULTS: Malnutrition was observed in 51 % of patients after CRT and in 29 % at surgery. Malnutrition after CRT was associated with treatment tolerability, and malnutrition at surgery was significantly associated with AL, which significantly influenced DFS in stage 1-3 patients. CONCLUSION: Malnutrition caused by CRT is common and is associated with treatment tolerability and AL. Nutritional assessment and support seem indispensable for the rectal cancer patients receiving CRT. PMID- 26888782 TI - Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future. AB - The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes since they are operated in the laboratory at atmospheric pressure and room temperature, providing a rich source of reactive oxygen and nitrogen species (RONS). A great deal of research has been conducted into the role of reactive species in both the growth and treatment of cancer, where long-established radio- and chemo-therapies exploit their ability to induce potent cytopathic effects. In addition to producing a plethora of RONS, LTPs can also create strong electroporative fields. From an application perspective, it has been shown that LTPs can be applied precisely to a small target area. On this basis, LTPs have been proposed as a promising future strategy to accurately and effectively control and eradicate tumours. This review aims to evaluate the current state of the literature in the field of plasma oncology and highlight the potential for the use of LTPs in combination therapy. We also present novel data on the effect of LTPs on cancer stem cells, and speculatively outline how LTPs could circumvent treatment resistance encountered with existing therapeutics. PMID- 26888784 TI - Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II. AB - Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin-lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. An Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wild-type. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N-terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin(2) inserts into the membrane and we propose this as the first step in pore formation, mediated by the nisin N-terminus-lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation. PMID- 26888785 TI - A qualitative study of the barriers to procedural sedation practices in paediatric emergency medicine in the UK and Ireland. AB - INTRODUCTION: There is extensive literature on paediatric procedural sedation (PPS) and its clinical applications in emergency departments (EDs). While numerous guidance and policy documents exist from international bodies, there remains a lack of uniformity and consistency of PPS practices within EDs. PPS is now gaining traction in the UK and Ireland and this study aimed to describe existing PPS practices and identify any challenges to training and provision of ED-based PPS. METHODS: A qualitative approach was employed to capture data through a focus group interview. Nine consultants in emergency medicine (EM) participated, varying in years of experience, clinical settings (mixed adult and paediatric ED or paediatric only) and geographical location (UK and Ireland). The focus group was audio-recorded, transcribed verbatim and analysed using Attride Stirling's framework for thematic network analysis. RESULTS: The global theme 'The Future of PPS in EM-A UK and Ireland Perspective' emerged from the following three organising themes: (1) training and education of ED staff; (2) current realities of PPS in EDs and (3) PPS and the wider hospital community. The main findings were (1) there is variability in ED PPS practice throughout the UK and Ireland; (2) lack of formal PPS training for trainees is a barrier to its implementation as a standard treatment and (3) there is a lack of recognition of PPS at a College level as a specialised EM skill. CONCLUSIONS: Establishment of PPS as a standard treatment option in the emergency setting will require implementation of robust training into general and paediatric EM training. This should be supported and enhanced through national and international collaboration in EM-led PPS research and audit. PMID- 26888786 TI - Their Hands Have Lost Their Bones: Exploring Cultural Scripts in Two West African Affect Lexica. AB - Previous research has indicated the importance of embodiment in West African emotion lexica. The current study aims to explore the pervasiveness of this cultural script through the analysis of the emotional lexica of two West African languages (Ga and Ewe) from Southern Ghana that have been featured minimally in previous emotion research. The analysis indicated that embodiment was an important cultural script in both affective lexica. However, interpersonal representations of emotions were also present. Further, emotion words in the two languages differed in the more specific loci of emotions. PMID- 26888787 TI - Clinical predictors of patient related delay in the VIENNA ST-elevation myocardial infarction network and impact on long-term mortality. AB - BACKGROUND: While contributors to system delay in ST-elevation myocardial infarction (STEMI) are well described, predictors of patient-related delays are less clear. The aim of this study was to identify predictors that cause delayed diagnosis of STEMI in a metropolitan system of care (VIENNA STEMI network) and to investigate a possible association with long-term mortality. METHODS: The study population investigated consisted of 2366 patients treated for acute STEMI in the Vienna STEMI registry from 2003-2009. Multivariable regression modelling was performed for (a) onset of pain to first medical contact (FMC) as a categorical variable (pain-to-FMC?60 min versus >60 min: 'early presenters' versus 'late presenters'); and for (b) onset of pain-to-FMC (min) as a continuous variable. RESULTS: After multivariable adjustment, female sex (odds ratio (OR) 1.348; 95% confidence interval (CI) 1.013-1.792; p=0.04) and diabetes mellitus (OR 1.355; 95% CI 1.001-1.835; p=0.05) were independently associated with late presentation in STEMI patients, whereas cardiogenic shock (OR 0.582; 95% CI 0.368-0.921; p=0.021) was a predictor of early diagnosis. When onset of pain-to-FMC was treated as a continuous variable, female sex ( p=0.003), anterior infarction ( p=0.004) and diabetes mellitus ( p=0.035) were independently associated with longer delay, while hyperlipidaemia ( p=0.002) and cardiogenic shock ( p=0.017) were strong predictors of short pain-to-FMC times. Three-year-all cause mortality was 9.6% and 11.3% ( p=0.289) for early and late presenters, respectively. After adjustment for clinical factors (sex, age, diabetes, current smoking, hypertension, hyperlipidaemia, cardiogenic shock and location of myocardial infarction) only a trend for increased risk of all-cause death was observed for longer pain-to-FMC times in a cox regression model (hazard ratio (HR) 1.012; 95% CI 0.999-1.025 for every 10 min of delay; p=0.061). Interestingly, early presentation within one hour of symptom onset was not associated with three-year mortality survival (HR 1.031; 95% CI 0.676-1.573; p=0.886). CONCLUSION: In this all-comers study of STEMI patients in the VIENNA STEMI network, cardiogenic shock was the strongest predictor of short patient-related delays, whereas a history of diabetes and female sex were independent associated with late diagnosis in STEMI. After adjustment for clinical confounders, patient related delay did not significantly impact on long-term all-cause mortality. PMID- 26888788 TI - Impact of triggering event in outcomes of stress-induced (Takotsubo) cardiomyopathy. AB - BACKGROUND: Takotsubo syndrome is also known as stress cardiomyopathy because of the regularity with which it has been associated with physical or emotional stress. Such stress may well be a "trigger" of the syndrome. AIMS: This analysis was undertaken to describe our experience with this disorder and in particular to examine the effects of the underlying trigger on outcomes. METHODS: We conducted a retrospective review of the medical records of 345 consecutive patients treated at our institution from 2006 to 2014. All presented with acute cardiac symptoms, a characteristic left ventricular contraction pattern (typical, atypical), and no major obstructive coronary artery disease. Patients were grouped based on their triggering event: (a) medical illness; (b) post-operative period; (c) emotional distress; or (d) no identified trigger. Baseline demographic characteristics, death in hospital, length of stay in hospital, and cardiac complications were abstracted from the patients' medical records. RESULTS: The mean+/-SD age of the population was 72+/-12 years and 91% were women. No significant difference in baseline characteristics was noted between the groups except for a higher prevalence of African Americans in the group with a medical illness. ST elevation was noted in 13.3% of patients and the average peak troponin level was 5+/-12 ng/dl. An inotropic drug was required in 49 (14.2%) patients, an intra-aortic balloon pump in 37 (10.7%) patients, and mechanical ventilation in 54 (15.7%) patients; 43.5% required treatment in the intensive care unit. Overall, 12 (3.5%) patients died. In only two (16.7%) patients was a there a direct cardiac cause of death. In those patients in whom the cardiac manifestations seemed to be triggered by a medical illness, the death rate was 7.1% and this was significantly higher than in the other groups ( p=0.03). Medical illness (odds ratio=6.25, p=0.02) and ST elevation (odds ratio=5.71, p=0.04) were both significantly associated with death. CONCLUSIONS: Our study showed that different triggers for Takotsubo syndrome confer different prognoses, with medical illness conferring the worst prognosis. Overall, the in-hospital death rate was low and mostly related to non-cardiac death secondary to the underlying medical illness. Although an unidentified trigger was prevalent in a third of this population, efforts should be made to identify the triggering event to classify the risk group of patients with Takotsubo syndrome. PMID- 26888789 TI - Vinay Prasad on the use of exaggerated language in cancer research, and how it can mislead doctors, patients, and the public. PMID- 26888790 TI - Langerhans Cell Histiocytosis: Emerging Insights and Clinical Implications. AB - Langerhans cell histiocytosis is a disorder characterized by lesions that include CD207+ dendritic cells along with an inflammatory infiltrate. Langerhans cell histiocytosis has a highly variable clinical presentation, ranging from a single lesion to potentially fatal disseminated disease. The uncertainty as to whether Langerhans cell histiocytosis is a reactive or a neoplastic disease has resulted in a long-standing debate on this question, and the limited understanding of the pathogenesis of the disease has impeded clinical improvement for patients. The current standard of care for multisystem Langerhans cell histiocytosis, empirically derived chemotherapy with vinblastine and prednisone, cures fewer than 50% of patients, and optimal therapies for relapse and neurodegenerative disease remain uncertain. Recent research advances support a model in which Langerhans cell histiocytosis arises due to pathologic activation of the mitogen activated protein kinase (MAPK) pathway in myeloid precursors. Redefinition of Langerhans cell histiocytosis as a myeloid neoplastic disorder driven by hyperactive ERK supports the potential of chemotherapy with efficacy against immature myeloid cells, as well as mutation-specific targeted therapy. PMID- 26888791 TI - Langerhans Cell Histiocytosis Enters the Genomics Age. PMID- 26888792 TI - The Immunocompromised Traveler. PMID- 26888793 TI - Checkpoint Inhibitors and Urothelial Carcinoma: The Translational Paradigm. PMID- 26888794 TI - The Evolving Biology of Castration-Resistant Prostate Cancer: Review of Recommendations From the Prostate Cancer Clinical Trials Working Group 3. AB - In 2008, the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) developed consensus guidelines for clinical trial design and conduct that redefined trial endpoints, with a dual-objective paradigm: to (1) controlling, relieving, or eliminating disease manifestations at the start of treatment; and (2) preventing or delaying further disease manifestations. Clinical and translational research in prostate cancer has expanded our current-day understanding of the mechanisms of its pathogenesis, as well as the different clinicopathologic and molecular subtypes of the disease, and has improved the therapeutic armamentarium for the management of metastatic castration-resistant prostate cancer (CRPC). These new advances led to the development of the updated PCWG3 guidelines in 2015. In this review, we analyze our evolving understanding of the biology of CRPC, acquired resistance mechanisms, and emerging therapeutic targets in light of the updated PCWG3 guidelines. We present a joint perspective from the medical oncology and urologic disciplines on the ongoing efforts to advance clinical trial performance in order to discover new therapies for this fatal disease. PMID- 26888795 TI - Oslerian Genomics for Prostate Cancer Oncology. PMID- 26888798 TI - Shrinking meningioma. PMID- 26888797 TI - 'The worm that got away': parainfectious atypical optic neuritis associated with schistosomiasis infection. AB - Although optic neuritis is commonly associated with multiple sclerosis, patients with atypical optic neuritis require further investigations to exclude other associated conditions. We report a woman presenting with cough, fatigue, atypical optic neuritis with chiasmitis. She responded partially to corticosteroids and we subsequently found she had a ground-glass lung nodule. Follow-up CT scan of thorax at 12 months showed new parenchymal lung lesions that suggested schistosomiasis. Further questioning by a respiratory physician identified, in retrospect, a previous exposure history; serological testing confirmed schistosoma infection. She was treated with praziquantel and slowly improved clinically, with radiological improvement in the optic chiasm, regression of the parenchymal lung lesions but with the ground glass nodule unchanged. We diagnosed parainfectious optic neuritis associated with schistosomiasis, based upon exposure history, serological confirmation and radiological features, together with the response to treatment, and having excluded other causes of an atypical optic neuritis. PMID- 26888799 TI - Junior doctors' contract: the key questions. PMID- 26888796 TI - Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice. AB - BACKGROUND: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (omega-3) polyunsaturated fatty acids. Increasing central omega-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. METHODS: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 uM) or continuous 2-week infusion (1 uM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. RESULTS: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. CONCLUSION: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central omega-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID- 26888801 TI - [Lipid-lowering guideline related new concepts]. PMID- 26888802 TI - [Recommendation on non-invasive assessment of patients with suspect coronary artery disease]. PMID- 26888800 TI - Effectiveness of platelet inhibition on major adverse cardiac events in non cardiac surgery after percutaneous coronary intervention: a prospective cohort study. AB - BACKGROUND: Platelet inhibition is mandatory therapy after percutaneous coronary intervention (PCI). Withdrawal of oral antiplatelet agents has been linked to increased incidence of postoperative adverse cardiac events in post-PCI patients having non-cardiac surgery (NCS). There is limited knowledge of temporal changes in platelet inhibition in this high-risk surgical population. We therefore performed a multicentre prospective cohort study evaluating perioperative platelet function and its association with postoperative major adverse cardiac events (MACE). METHODS: In 201 post-PCI patients having NCS, we assessed the association between platelet function and postoperative MACE. We performed perioperative platelet function testing using a platelet mapping assay (PMA). Troponin-I was measured every 8 h for 2 days, then daily until day 5. Myocardial infarction was assessed using the third universal definition. We used multivariable logistic regression to assess the association between platelet inhibition and MACE. RESULTS: Major adverse cardiac events occurred in 40 patients within 30 days of surgery. Thirty-two of these events were non-ST elevation myocardial infarction, four ST-elevation myocardial infarction, and four exacerbation of congestive heart failure. We were unable to show an association between platelet inhibition and MACE. The PMA showed declining levels of platelet inhibition the longer the antiplatelet therapy was withheld before surgery. Logistic regression did not show an association between preoperative platelet function or the type of stent and MACE. We found an increased cardiac risk of MACE after surgery within 6 weeks of PCI. CONCLUSIONS: The incidence of MACE in patients undergoing NCS after previous PCI is high in spite of adequate perioperative antiplatelet therapy. CLINICAL TRIAL REGISTRATION: NCT 01707459 (registered at http://www.clinicaltrials.gov). PMID- 26888804 TI - [Relationship between hyperhomocysteine and long-term outcome of coronary artery disease patients after drug-eluting stent implantation]. AB - OBJECTIVE: To explore the relationship between hyperhomocysteinemia (H-Hcy) and long-term outcome of coronary artery disease (CAD) patients after drug-eluting stent (DES) implantation in a single centre. METHODS: A total of 1 408 consecutive patients implanted with DES in our department between March 2011 and January 2013 were enrolled in this prospective study. Patients were stratified into H-Hcy (Hcy>=10 umol/L, n=798, 56.7%) and non-H-Hcy group (Hcy<10 umol/L, n=610, 43.3%). The clinical characteristics, coronary artery lesions, SYNTAX score and 1-year major adverse cardiac and cerebrovascular events (MACCE) were compared between the two groups. RESULTS: Compared with non-H-Hcy group, coronary artery stenosis was severer as shown by higher diseased arteries (2.11+/-0.87 vs. 1.91+/-0.82, P<0.001), higher incidence of three diseased arteries (39.7% vs. 29.5%, P<0.001) and higher SYNTAX score (36.99+/-29.66 vs. 27.39+/-22.70, P=0.001) in H-Hcy group. The 1-year incidence of MACCE was also higher in H-Hcy group compared with non-H-Hcy group(18.4% vs. 8.9%, P<0.001). Multivariate Cox analysis showed that diabetes mellitus (OR=1.530, 95%CI 1.142-2.050, P=0.004), age (OR=1.065, 95%CI 1.038-1.093; P<0.001), and Hcy (OR=1.019, 95%CI 1.005-1.033, P=0.009) are the independent predictors for 1-year MACCE. CONCLUSION: High Hcy level is correlated with the severity of coronary artery stenosis, and serves as an independent predictor of MACCE after stenting in CAD patients. PMID- 26888803 TI - [Association between very low density lipoprotein cholesterol and cholesterol absorption/synthesis markers in patients with moderate and high risk of coronary heart disease]. AB - OBJECTIVE: To evaluate the association between very low density lipoprotein cholesterol (VLDL-C) and cholesterol absorption and synthesis markers in patients with moderate and high risk of coronary heart disease. METHODS: A total 363 statin-naive patients with moderate and high risk of coronary heart disease were consecutively recruited from two hospitals in Shanxi and Henan provinces between October 2008 and June 2009. A standard questionnaire and physical examination were performed at baseline. Atorvastatin (20 mg/day) was administered to patients for 4 weeks. Venous blood samples after an overnight fast were collected before and after treatment for measuring VLDL-C and cholesterol absorption and synthesis markers. In qualitative analyses, the baseline level of cholesterol absorption and synthesis markers and their reduction after atorvastatin treatment were categorized into 3 tertile groups. RESULTS: (1) Of 363 patients, 283 patients with mean age of (55.43+/-9.01)years old with complete data were finally analyzed. The median level of baseline VLDL-C was 1.06 (0.65, 1.86) mmol/L. The median level of baseline cholesterol absorption marker (Campesterol) and cholesterol synthesis marker (Lathosterol) was 6.01 (3.78, 9.45) mg/L and 13.46 (8.30, 21.07) mg/L, respectively. (2) Partial correlation analysis and multiple regression showed the baseline level of VLDL-C was positively correlated with Campesterol (r=0.153, P<0.05) but not with Lathosterol(r=0.182, P=0.173). Furthermore, baseline VLDL-C level significantly increased with tertile of the baseline level of Campesterol in the qualitative analyses(P for trend=0.035). (3) Mean reduction in VLDL-C levels was 38.0% after 4 weeks atorvastatin treatment. VLDL-C reduction was positively correlated with Campesterol reduction (r=0.331, P<0.001). VLDL-C reduction significantly increased with the tertile of Campesterol reduction (P for trend=0.032). But this trend was not observed between VLDL-C level and Lathosterol (P for trend=0.798). CONCLUSION: The level of VLDL-C was closely related to cholesterol absorption marker, and further studies are needed to validate if inhibitor of cholesterol absorption (for example by Ezetimibe) could bring about more effective VLDL-C lowering effect in this patient cohort. PMID- 26888805 TI - [Pathological characteristics of coronary artery disease in elderly patients aged 80 years and over]. AB - OBJECTIVE: To define the pathological changes of coronary artery and compare the clinical diagnosis and pathological diagnosis differences in elderly patients aged 80 and over. METHODS: A total of 909 autopsy cases aged 60-100 years in our hospital from April 1st 1969 to October 31th 2013 were analyzed. The prevalence and pathological features of coronary artery disease (CAD) in cases aged 80 years and over were compared with those aged 60-79 years old. The misdiagnosis and missed diagnosis rate were calculated. RESULTS: The prevalence of CAD by autopsy (63.8% (289/453) vs. 39.9% (182/456), P<0.01), old myocardial infarction (OMI) by autopsy (63.0% (182/289) vs. 51.6% (94/182), P<0.05) and chronic myocardial ischemia by autopsy (22.5% (65/289) vs. 7.1% (13/182), P<0.01) were significantly higher while the prevalence of acute myocardial infarction (AMI) by autopsy was significantly lower (22.1% (64/289) vs. 42.9% (78/182), P<0.01) in aged 80 and over group compared to 60-79 years old group. The misdiagnosis rate of CAD was 65.2% (107/164), the missed diagnosis rate of OMI was 62.1% (113/182) and the missed diagnosis rate of AMI was 37.5% (24/64) in the aged 80 and over group. CONCLUSIONS: The prevalence of CAD and misdiagnosis and missed diagnosis rate are high in dead inpatients aged 80 years and over. OMI is more common but often missed in this group. Thus, the diagnosis and evaluation of CAD should be enhanced in this patient group. PMID- 26888806 TI - [Effects of pretreatment with recombinant human B-type natriuretic peptide on infarct size in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention]. AB - OBJECTIVES: To investigate whether the administration of recombinant human B-type natriuretic peptide (rhBNP) before primary percutaneous coronary intervention (PCI) could further limit the infract size, improve left ventricular function, and alleviate cardiac dilation in patients with acute ST-segment elevation myocardial infarction(STEMI). METHODS: A total of 93 consecutive patients presenting chest pain within 12 hours from the onset, suspicious of first STEMI located at anterior wall undergoing primary PCI, were eligible for enrollment and randomly assigned to either rhBNP group (rhBNP administration starting at 5 min before PCI, 1.5 ug/kg bolus intravenous injection followed by 0.007 5-0.03 ug.kg( 1).min(-1) for up to 120 hours, n=48) or nitroglycerin (NIT) group (NIT treatment starting at 5 min before PCI, 10-100 ug/min intravenous infusion for 120 hours, n=45). Primary PCI was performed in both groups using post-conditioning (PC) technique. TIMI flow grade, corrected TIMI frame count, and TIMI myocardial perfusion grade were compared between the two groups at the time of infarct related artery (IRA) re-patency. The levels of serum creatine kinase MB isoenzyme (CK-MB) and troponin I (TnI) were measured. Echocardiography was performed at baseline 7 days and 6 months later. RESULTS: Baseline characteristics were similar between the two groups. The percentage of TIMI grade 3 and TIMI myocardial perfusion grade 3 after PCI both tended to be higher in rhBNP group than those in NIT group (95.8%(46/48) vs. 86.7%(39/45), P=0.162) and (72.9%(35/48) vs. 62.2%(28/45), P=0.500). The corrected TIMI frame count was significantly decreased in rhBNP group (21.0+/-8.7 vs. 28.2+/-14.8, P=0.005). The myocardial infarct size expressed as the AUC of CK-MB ((3 249+/-1 101) U/L vs. (4 474+/-1 661)U/L, P=0.010) or AUC of TnI ((3 670+/-942) ug/L vs. (4 541+/-1 098) ug/L, P=0.021) was significantly decreased in rhBNP group compared with those in NIT group. At 7 days after primary PCI, the left ventricular ejection fraction (LVEF) tended to be higher (P>0.05), while the E/e' index and wall motion score index (WMSI) ((11.95+/-3.31 vs. 14.60+/-4.09, P=0.030) and (1.74+/-0.17 vs. 2.40+/-0.55, P<0.001)) were significantly improved in rhBNP group compared with those in NIT group. BNP level was also significantly lower in rhBNP group compared that in NIT group ((68.3+/-37.8) ng/L vs. (129.4+/-64.4) ng/L, P<0.001). During 6-month follow-up, LVEF and WMSI were significantly improved in rhBNP group compared those in NIT group(51.7%+/-12.7% vs. 46.9%+/-9.6%, P=0.024 and 1.69+/-0.35 vs. 1.92+/-0.47, P=0.020). CONCLUSION: Administration of rhBNP before PCI with post-conditioning procedure can further improve myocardial perfusion, limit myocardial infarct size, ameliorate cardiac dysfunction and postpone left ventricular early-stage and long-term remodeling in STEMI patients undergoing primary PCI. PMID- 26888807 TI - [Clinical characteristics and cardiac imaging features of patients with cardiac amyloidosis]. AB - OBJECTIVE: To summarize the clinical characteristics and cardiac imaging features by focusing the diagnostic value of MRI in patients with cardiac amyloidosis (CA). METHODS: A total of 31 cases with pathologically proven CA from January 2013 to December 2014 were included in this retrospective study. RESULTS: Patients expressed typical disease manifestations at a late age (54+/-11) years. Majority patients were male (20 cases, 64.5%) in this cohort. Blood pressure was normal, 13 cases (42.9%) presented with edema in lower limbs, 12 cases (38.7%) with chest distress and dyspnea and 9 cases (29.0%) with abdominal pain and diarrhea. Electrocardiogram (ECG) features were as follows: 20 cases (64.5%) with low voltage in limb leads, 20 cases (64.5%) with poor R-wave progression in precordial leads, 17 cases (54.8%) with pseudo-necrotic Q wave and 27 cases (87.1%) with ST-T changes. Echocardiography examination showed that 25 (80.6%) of 31 cases were with left atrial enlargement, 22 cases (71%) with increased ventricular septal thickness and 12 cases (38.7%) with myocardial ground-glass opacity, 24 cases (77.4%) presented restrictive left ventricular filling pattern, 14 cases (45.2%) showed impaired left ventricular systolic function and 10 cases (32.3%) expressed abnormal left ventricular eject function (<50%). Cardiac MRI features were as follows: among 31 patients, 7 patients underwent cardiac MRI. Left ventricular and interventricular septum hypertrophy were vsulized in 6 cases, increased thickness of interatrial spetum in 3 cases, left atrial enlargement in 4 cases and right atrial enlargement in 3 cases. MRI also revealed a distinct diffuse delayed gadolinium enhancement of subendocardial and interventricular septum in 3 cases, 1 of which was with delayed enhancement of interatrial spetum. CONCLUSIONS: Clinically, CA diagnosis should be considered for patients with manifestations of chest distress and edema in lower limbs, ECG features of low voltage in limb leads, poor R-wave progression and pseudo necrotic Q wave, myocardial hypertrophy with myocardial ground-glass opacity in echocardiography and a characteristic MRI pattern of diffuse subendocardial delayed gadolinium enhancement even without the pathological proof. PMID- 26888809 TI - [Value of a novel categorization of congenital double-outlet right ventricle on guiding the choice of surgical approaches]. AB - OBJECTIVE: To explore the feasibility and value of a new categorization of double outlet right ventricular (DORV) on guiding the optimal choices of surgical approaches. METHODS: Five hundred and twenty one DORV patients diagnosed by echocardiography, angiocardiography and CT at Fuwai Hospital from May 2003 to September 2014 were enrolled in this retrospective study. Congenital DORV was categorized according to three basic factors as follows: the positional relationships of great arteries (normal relation or abnormal relation), the relationships of the ventricular septal defect (VSD) to the great arteries (committed VSD or remote VSD), the presence or absence of pulmonary outflow tract obstruction (POTO). Eight types of DORV were established: type I (normal relation, committed VSD, without POTO), type II (normal relation, committed VSD, POTO), type III (normal relation, remote VSD, without POTO), type IV (normal relation, remote VSD, POTO), type V (abnormal relation, committed VSD, without POTO), type VI (abnormal relation, committed VSD, POTO), type VII (abnormal relation, remote VSD, without POTO), type VIII (abnormal relation, remote VSD, POTO). Feasibility of this classification and the value of this classification on guiding the choice of surgical approaches were analyzed. RESULTS: Among the five hundred and twenty one patients, there were 90 patients (17.3%) with type I DORV, 94 patients (18.0%) with type II, 33 patients (6.3%) with type III, 34 patients (6.5%) with type IV, 64 patients (12.3%) with type V, 61 patients (11.7%) with type VI, 33 patients (6.3%) with type VII, 112 patients (21.5%) with type VIII. Thus, all patients could be typed by this classification method. The echocardiography diagnosis was consistent with the intra-operative and or cardiac catheterization/CT findings. Excluding the contraindications of bi-ventricular repair, different surgical approaches were performed in every subtype of DORV according the classification, which indicated that this novel categorization could accurately guide the clinic managements. CONCLUSION: This novel DORV categorization can accurately diagnose DORV lesions, and guide the clinic therapy choice. PMID- 26888808 TI - [Survey and analysis on sources of reference intervals and distribution of medical decision levels in NT-proBNP, BNP and homocysteine]. AB - OBJECTIVE: To analyze the sources of reference intervals and distribution of medical decision levels in NT-proBNP, BNP and homocysteine (Hcy) based on the feedback of laboratories which participated in the 2014 External Quality Assessment (EQA) program in China. METHODS: Information of reference intervals and medical decision levels was collected from the 2014 EQA programs in NT proBNP, BNP and Hcy.All the abnormal values and errors were eliminated.Data were analyzed by SPSS 13.0 and Microsoft Excel 2007 in terms of referring to sources of reference intervals and distribution of medical decision levels.Values were further grouped based on instrument system for NT-proBNP and BNP, reagent manufacturers for Hcy. RESULTS: There were 330, 119 and 339 laboratories submitting the data on the reference intervals of NT-proBNP, BNP and Hcy. Only 133, 54 and 102 laboratories provided information about medical decision levels.Most reference sources were derived from reagent manufactures (NT-proBNP 76.97%(254/330), BNP 89.08%(106/119), Hcy 83.19%(282/339)). Approximately, 36.53%(122/334), 45.38%(54/119) and 47.95%(164/342) of the laboratories validated the reference intervals of NT-proBNP, BNP and Hcy.According to the surveys, the mean and median values were not close to each other (NT-proBNP 507.99 ng/L and 300.00 ng/L, BNP 342.72 ng/L and 100.00 ng/L, Hcy 17.34 umol/L and 15.00 umol/L). Variation of P2.5 and P97.5 was as follows: (NT-proBNP 125.00-1 800.00 ng/L, BNP 87.50-4562.50 ng/L, Hcy 4.15-50.00 umol/L). The ranges were NT-proBNP 60.00-7 000.00 ng/L, and BNP 80.00-7 000.00 ng/L, and Hcy 1.5-52.00 umol/L.P values of rank sum test for NT-proBNP, BNP and Hcy were 0.449, 0.208 and 0.754. CONCLUSIONS: Medical decision levels of NT-proBNP, Hcy and BNP showed large variation among laboratories and the sources of reference interval were not unified.Thus, urgent efforts should be made to establish appropriate reference intervals for Chinese people and promote harmonization and standardization of reference intervals and medical decision levels on BNP, NT-proBNP and Hcy. PMID- 26888810 TI - [Relationship between new-onset atrial fibrillation and sympathetic neural remodeling in a canine acute myocardial infarction model]. AB - OBJECTIVE: To establish the canine model of new-onset atrial fibrillation (AF) after acute myocardial infarction (AMI), and explore the relationship between new onset AF and sympathetic neural remodeling in this model. METHODS: Twenty four adult mongrel dogs were randomly divided into 4 groups by applying random number table. Group A (n=6): ligate the left circumflex artery (LCX). Group B (n=6): ligate the LCX and right atrial anterior artery and right atrial middle artery. Group C (n=6): ligate left anterior descending artery.Group D (n=6): sham operation.Sequential electrophysiology study was performed in all dogs to determine the AF induction rate, AF duration, effective refractory period (ERP), the density of tyrosine hydroxylase (TH) and norepinephrine transporter (NET) before AMI or sham operation, and at 30 min, 2 hours and 4 hours after AMI or sham operation. RESULTS: (1) The highest AF induction rate of right atrium and left auricle was 96.7%(58/60) and 95.0%(57/60) in group B, 81.7%(49/60) and 38.3%(23/60) in group A, 28.3%(17/60) and 35.0%(21/60) in group C, 20.0%(12/60) and 33.3%(20/60) in group D. (2) At 4 hours after AMI, AF duration was significantly prolonged in group B(193.50+/-54.67) s, compared with group A(53.83+/-9.37) s, group C(45.00+/-19.50) s, and group D(16.67+/-4.50) s (all P<0.05). (3) In group B, the ERP of AF was prolonged at 30 minutes after AMI and shortened at 2 hours and 4 hours after AMI compared with baseline level(all P<0.05). (4) The TH density of left atrium ((3 485+/-694) um2/mm2) and left auricle((2 645+/-454) um2/mm2) in group A and the TH density of left atrium ((7 873+/-1159) um2/mm2) and left auricle((3 070+/-605) um2/mm2) in group B were significantly higher than those in group C ((1 474+/-475) um2/mm2, (1 177+/-277) um2/mm2) and group D ((678+/-206) um2/mm2, (489+/-125) um2/mm2) (all P<0.05), and the TH density of right atrium and right auricle in group B were higher than group A (all P<0.05). The NET density of left atrium((476+/-75) um2/mm2) and left auricle ((414+/-52) um2/mm2) in group A and the NET density of left atrium((527+/ 81) um2/mm2) and left auricle((429+/-85) um2/mm2) in group B were lower than that in group C ((1 044+/-105) um2/mm2, (867+/-67) um2/mm2) and group D ((1 438+/-60) um2/mm2, (1 027+/-119) um2/mm2) (all P<0.05). CONCLUSIONS: Ligating the LCX, right atrial anterior artery and right atrial middle artery at the same time can significantly increase the success rate in establishing the canine model of new onset atrial fibrillation after acute myocardial infarction and can also increase the AF duration.Cardiac sympathetic remodeling after acute myocardial infarction is associated with induction and duration of AF. PMID- 26888811 TI - [Correlation between long time systolic blood pressure variability and short time systolic blood pressure in aged population]. AB - OBJECTIVE: To investigate the correlation between long time systolic blood pressure variability(SBPV)and short time SBPV in aged population. METHODS: A total of 752 subjects aged >=60 years of Kailuan Group who took part in 2006 2007, 2008-2009, 2010-2011 and 2012-2013 health examination were included by cluster sampling method.Long time SBPV was calculated by standard deviation of mean systolic blood pressure measured in 2006-2007, 2008-2009, 2010-2011 and 2012 2013, standard deviation represents short time systolic blood pressure which is derived from 24 hour ambulatory blood pressure monitoring. The observation population was divided into three groups according to the third tertiles of the time systolic blood pressure variability: the first point(<9.09 mmHg (1 mmHg=0.133 kPa)), second point (>=9.09 mmHg, and <14.29 mmHg), and third point (>=14.29 mmHg). Multivariate logistic regression analysis was used to analyze the correlation between long time systolic blood pressure variability and short time systolic blood pressure. RESULTS: (1) The participants' age were (67.0+/-5.7) years old (284 women). (2) The 24 hours and daytime SSD were (14.7+/-4.0) mmHg, (14.7+/-3.5) mmHg, (15.7+/-4.4) mmHg (P=0.010) and (14.1+/-4.4) mmHg, (14.2+/ 3.5) mmHg and (15.4+/-4.6) mmHg (P<0.001) according to the tertiles of long time systolic blood pressure variability, respectively, nighttime SSD were (12.0+/ 4.4) mmHg, (11.8+/-4.8) mmHg and (11.9+/-4.9) mmHg (P=0.900). (3) Multiple logistic regression analysis showed that the tertiles of long time SSD was the risk factor for increasing daytime SSD>14.00 mmHg (OR=1.51, 95%CI: 1.03-2.23, P=0.037), but not a risk factor for increasing 24 hours SSD>14.41 mmHg (OR=1.10, 95%CI: 0.75-1.61, P=0.639) and nighttime SSD>11.11 mmHg (OR=0.98, 95%CI: 0.67 1.42, P=0.899). CONCLUSION: Increased long time SBPV is a risk factor for increasing daytime SBPV. PMID- 26888812 TI - [Impact of metabolic risk factors and lifestyle on new onset hypertension in Beijing community residents]. AB - OBJECTIVE: To explore if the new onset hypertension was related with metabolic risk factors and lifestyle in Beijing community residents to guide the targeted prevention of hypertension. METHODS: A population-based survey with a randomly cluster sampling was made to observe the relationship between metabolic risk factors and lifestyle with new onset hypertension by multivariate and logistic regression. RESULTS: A total of 4 034 subjects with normal blood pressure at baseline were included and 978 (24.2%) residents developed hypertension two years later. Multiple logistic analysis demonstrated that risk factors that contributed to new onset hypertension were prehypertension, overweight, obesity, frequent alcohol drinking, metabolic syndrome (MS), age and male gender, the respective Odds Ratios(OR) and 95% confidence interval (95%CI) are as follows: 3.512 (2.965 4.168), 1.654 (1.423-1.918), 2.264 (1.633-2.951), 1.493 (1.231-1.775), 1.329 (1.227-1.414), 1.226 (1.115-1.335), 1.135(1.018-1.221). College education serves as the protective factor, and the OR (95%CI) was 0.692 (0.476, 0.897). CONCLUSIONS: New onset hypertension in Beijing community residents is mainly related with prehypertension, overweight or obesity, MS, frequent alcohol drinking and low education level. We should pay more attention to modulating metabolic risk factors and lifestyle to reduce the new onset hypertension in China. PMID- 26888813 TI - [Impact of statin therapy on recurrence of persistent atrial fibrillation after electrical cardioversion: a meta-analysis]. AB - OBJECTIVE: To evaluate the impact of statin therapy on the recurrence rate in patients with persistent atrial fibrillation (AF) after electrical cardioversion. METHODS: PubMed, EMBbase, Cochrane central register of controlled trials were searched up to February 2015 to identify randomized controlled trials, which reported the effect of statin therapy on AF recurrence after electrical cardioversion. The data were analyzed by RevMan 5.3 and Stata 12.0 software. RESULTS: Six trials with 572 patients were included. The result showed that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion (OR=0.60, 95%CI: 0.32-1.11, P>0.05) compared with controls. Four out of the six trials investigated the effect of atorvastatin on the recurrence rate of AF after electrical cardioversion, subgroup analysis of these trials showed that compared with controls, atorvastatin had no effect on the recurrence of AF after electrical cardioversion (OR=0.59, 95%CI: 0.25-1.39, P>0.05). Three out of the six trials had high quality (Jadad score>=3), subgroup analysis of these trials also showed that statins did not affect the recurrence rate of AF after electrical cardioversion (OR=0.76, 95%CI: 0.49-1.16, P>0.05). CONCLUSION: This analysis suggested that statin therapy had no effect on the recurrence rate in patients with persistent AF after electrical cardioversion. PMID- 26888814 TI - [Report of a young patient suffered from acute myocardial infarction post methamphetamine inhalation]. PMID- 26888815 TI - [Loffler endocarditis and cardiac embolism in a patient with eosinophilic leukemia]. PMID- 26888816 TI - [One case of delayed cardiac tamponade after coronary artery bypass grafting]. PMID- 26888817 TI - [Stress cardiomyopathy in a patient with myasthenia gravis]. PMID- 26888818 TI - [Update on the efficacy of dual or triple antiplatelet therapy in patients with acute coronary syndrome]. PMID- 26888819 TI - [Progress on the role of long non-coding RNAs in cardiovascular diseases]. PMID- 26888820 TI - [Autophagy in atherosclerosis: a potential target to alleviate vascular endothelial cell dysfunction]. PMID- 26888821 TI - New life in overactive bladder. Focus on "Novel regulatory mechanism in human urinary bladder: central role of transient receptor potential melastatin 4 channels in detrusor smooth muscle function". PMID- 26888824 TI - Correlation between tobacco control policies, consumption of rolled tobacco and e cigarettes, and intention to quit conventional tobacco, in Europe. AB - OBJECTIVE: To analyse the correlation between the implementation of tobacco control policies and tobacco consumption, particularly rolling tobacco, electronic cigarettes (e-cigarettes) users and the intent to quit smoking in 27 countries of the European Union. DESIGN: Ecological study with the country as the unit of analysis. DATA SOURCES: We used the data from tobacco control activities, measured by the Tobacco Control Scale (TCS), in 27 European countries, in 2010, and the prevalence of tobacco consumption data from the Eurobarometer of 2012. ANALYSIS: Spearman correlation coefficients (rsp) and their 95% CIs. RESULTS: There was a negative correlation between TCS and prevalence of smoking (rsp= 0.41; 95% CI -0.67 to -0.07). We also found a negative correlation (rsp=-0.31) between TCS and the prevalence of ever e-cigarette users, but it was not statistically significant. Among former cigarette smokers, there was a positive and statistically significant correlation between TCS and the consumption of hand rolled tobacco (rsp=0.46; 95% CI 0.06 to 0.70). We observed a similar correlation between TCS and other tobacco products (cigars and pipe) among former cigarette smokers. There was a significant positive correlation between TCS and intent to quit smoking in the past 12 months (rsp=0.66; 95% CI 0.36 to 0.87). CONCLUSIONS: The level of smoke-free legislation among European countries is correlated with a decrease in the prevalence of smoking of conventional cigarettes and an increase in the intent to quit smoking within the past 12 months. However, the consumption of other tobacco products, particularly hand-rolled tobacco, is positively correlated with TCS among former cigarette smokers. Therefore, tobacco control policies should also consider other tobacco products, such as rolling tobacco, cigars and pipes. PMID- 26888822 TI - Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies. AB - OBJECTIVES: To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis of randomised and observational studies. DATA SOURCES: Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. ELIGIBILITY CRITERIA: Randomised controlled trials, non-randomised controlled trials, cohort studies, and case control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. DATA COLLECTION AND ANALYSIS: Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. RESULTS: Eligible studies included 43 trials (n=68,775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1,777,358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15,701 v 33/12,591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18,554 v 552/18,474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. CONCLUSIONS: The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use. PMID- 26888825 TI - Tackling the public health needs of refugees. PMID- 26888826 TI - How effective are platelet rich plasma injections in treating musculoskeletal soft tissue injuries? PMID- 26888827 TI - The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer. AB - PURPOSE: Approved anti-EGFR antibodies cetuximab and panitumumab provide significant clinical benefit in patients with metastatic colorectal cancer (MCRC). However, patients ultimately develop disease progression, often driven by acquisition of mutations in the extracellular domain (ECD) of EGFR. Sym004 is a novel 1:1 mixture of two nonoverlapping anti-EGFR mAbs that recently showed promising clinical activity in a phase I trial in MCRC. Our aim was to determine the efficacy of Sym004 to circumvent cetuximab resistance driven by EGFR ECD mutations. EXPERIMENTAL DESIGN: Functional studies were performed to assess drug receptor binding as well as ligand-dependent activation of individual EGFR mutants in the presence of cetuximab, panitumumab, and Sym004. Cell viability and molecular effects of the drugs were assayed in cetuximab-resistant cell lines and in tumor xenograft models. Efficacy of Sym004 was evaluated in patients progressing to cetuximab that harbored EGFR mutation in the post-cetuximab tumor sample. RESULTS: Contrary to cetuximab and panitumumab, Sym004 effectively bound and abrogated ligand-induced phosphorylation of all individual EGFR mutants. Cells resistant to cetuximab harboring mutations in EGFR maintained sensitivity to Sym004, which was consistent with an effective suppression of EGFR downstream signaling, translating into profound and sustained tumor regression in the xenograft model. As proof-of-principle, a patient with a tumor harboring an EGFR mutation (G465R) following cetuximab therapy benefited from Sym004 therapy. CONCLUSIONS: Sym004 is an active drug in MCRC resistant to cetuximab/panitumumab mediated by EGFR mutations. EGFR mutations are potential biomarkers of response to Sym004 to be evaluated in ongoing large clinical trials. Clin Cancer Res; 22(13); 3260-7. (c)2016 AACR. PMID- 26888828 TI - Research Priorities, Measures, and Recommendations for Assessment of Tobacco Use in Clinical Cancer Research. AB - There is strong evidence that cigarette smoking causes adverse outcomes in people with cancer. However, more research is needed regarding those effects and the effects of alternative tobacco products and of secondhand smoke, the effects of cessation (before diagnosis, during treatment, or during survivorship), the biologic mechanisms, and optimal strategies for tobacco dependence treatment in oncology. Fundamentally, tobacco is an important source of variation in clinical treatment trials. Nevertheless, tobacco use assessment has not been uniform in clinical trials. Progress has been impeded by a lack of consensus regarding tobacco use assessment suitable for cancer patients. The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force identified priority research areas and developed recommendations for assessment items and timing of assessment in cancer research. A cognitive interview study was conducted with 30 cancer patients at the NIH Clinical Center to evaluate and improve the measurement items. The resulting Cancer Patient Tobacco Use Questionnaire (C-TUQ) includes "Core" items for minimal assessment of tobacco use at initial and follow-up time points, and an "Extension" set. Domains include the following: cigarette and other tobacco use status, intensity, and past use; use relative to cancer diagnosis and treatment; cessation approaches and history; and secondhand smoke exposure. The Task Force recommends that assessment occur at study entry and, at a minimum, at the end of protocol therapy in clinical trials. Broad adoption of the recommended measures and timing protocol, and pursuit of the recommended research priorities, will help us to achieve a clearer understanding of the significance of tobacco use and cessation for cancer patients. PMID- 26888829 TI - Mitochondrial Reprogramming Regulates Breast Cancer Progression. AB - PURPOSE: The goal of this study was to understand the role of altered mitochondrial function in breast cancer progression and determine the potential of the molecular alteration signature in developing exosome-based biomarkers. EXPERIMENTAL DESIGN: This study was designed to characterize the critical components regulating mitochondrial function in breast tumorigenesis. Experiments were conducted to assess the potential of these molecules for exosome-based biomarker development. RESULTS: We observed a remarkable reduction in spontaneous metastases through the interplay in mitochondria by SH3GL2, vesicular endocytosis associated protein and MFN2, an important regulator of mitochondrial fusion. Following its overexpression in breast cancer cells, SH3GL2 translocated to mitochondria and induced the production of superoxide and release of cytochrome C from mitochondria to the cytoplasm. These molecular changes were accompanied by decreased lung and liver metastases and primary tumor growth. SH3GL2 depletion reversed the above phenotypic and associated molecular changes in nontumorigenic and tumorigenic breast epithelial cells. Loss of SH3GL2 and MFN2 expression was evident in primary human breast cancer tissues and their positive lymph nodes, which was associated with disease progression. SH3GL2 and MFN2 expression was detected in sera exosomes of normal healthy women, but barely detectable in the majority of the women with breast cancer exhibiting SH3GL2 and MFN2 loss in their primary tumors. CONCLUSIONS: This study identified a new mitochondria reprogramming pathway influencing breast cancer progression through SH3GL2 and MFN2. These proteins were frequently lost in breast cancer, which was traceable in the circulating exosomes. Clin Cancer Res; 22(13); 3348-60. (c)2016 AACR. PMID- 26888830 TI - Facial soft tissue changes during the pre-pubertal and pubertal growth phase: a mixed longitudinal laser-scanning study. AB - BACKGROUND/OBJECTIVES: Facial soft tissues changes during growth roughly tend to mimic the underlying hard tissues, but not completely. The aim of this mixed longitudinal study was to assess facial growth among pre-pubertal and pubertal subjects without malocclusion using a non-invasive three-dimensional laser scanning system. SUBJECTS/METHODS: Fifty-nine subjects (30 females and 29 males) aged at baseline 5.4-8.9 years with normal occlusion were clustered into the younger, older pre-pubertal, and pubertal groups according to age and the absence/presence of a standing height growth spurt. Three-dimensional facial images were obtained using laser scanners for five consecutive years. Several transversal, sagittal, and vertical parameters were assessed for between and within group comparisons. RESULTS: Significant overall changes of almost all parameters were seen within each group (P < 0.05) without any group differences (P > 0.05). The younger pre-pubertal group showed greater annual growth rates of lip prominence; both pre-pubertal groups showed greater rates in facial middle third height. The pubertal group showed greater annual rates in facial profile angle changes during the growth peak. LIMITATIONS: A high standing height increment (7cm) was used as the threshold for subject allocation in the pubertal group. CONCLUSIONS: Soft tissue facial growth has generally similar amounts and rates irrespective of the pubertal growth spurt. Pre-pubertal subjects show greater annual rates of facial middle third height changes while pubertal subjects show greater annual rates of chin protrusion. PMID- 26888831 TI - Disease and functional loading effect on the structural conformation and mechanical properties of the mandibular condyle in a transgenic rheumatoid arthritis murine model: an experimental study. AB - AIM: The aim of the present study was to investigate the effect of rheumatoid arthritis (RA) and functional loading through diet modification on the structural conformation and the mechanical properties of the mandibular condyle in a transgenic mouse model and compare to healthy littermates. MATERIALS AND METHODS: Four-week-old hybrid male mice from mixed background CBAxC57BL/6 were used. Four groups of animals were formed consisting of five animals each, either presenting RA (transgenic line hTNF 197), or wild-type (control), half receiving ordinary (hard) diet and half receiving soft diet within each category. Following sacrifice, resin-embedded and metallographically polished condylar specimens were evaluated employing scanning electron microscopy/ Energy dispersive x-ray spectroscopy and also tested for mechanical properties, through Vickers microhardness (HV100) measurements. RESULTS: The multivariable analysis revealed significantly lower HV100 values for the RA groups after adjusting for diet (beta = -10; 95% confidence interval: -16, -4; P = 0.001), while functional loading through diet modification did not appear as a significant predictor of the outcome. CONCLUSIONS: There was evidence of compromised mechanical properties of the mandibular condylar bone for the diseased animals, whereas no association between functional loading and mechanical properties of the condyle could be established. PMID- 26888832 TI - [The epidemiological profile of heart failure patients in China]. PMID- 26888833 TI - [Clinical application of N-terminal pro-B-type natriuretic peptide measurements in heart failure patients]. PMID- 26888834 TI - [A novel therapy option for heart failure with dual angiotensin receptor and neprilysin inhibition]. PMID- 26888835 TI - [Correlation between VE/VCO2slope and echocardiographic derived systolic pulmonary artery pressure in patients with chronic heart failure]. AB - OBJECTIVE: To explore the relationship between ventilator efficiency of cardiopulmonary exercising test (the slope of the relation between ventilation and carbon dioxide production, VE/VCO(2)slope) and systolic pulmonary artery pressure (sPAP) measured by echocardiography in patients with chronic heart failure (HF). METHODS: Data from 86 HF patients who were treated in Fuwai Hospital between December 2012 and July 2014 and performed the symptom limited maximal cardiopulmonary exercise test (CPET) and echocardiography were retrospectively analyzed.H F patients were divided into 3 groups (mild, moderate and severe) according to the maximum oxygenconsumption (peakVO(2)). RESULTS: There is a significant linear correlation between VE/VCO(2)slope and sPAP (r=0.260, P=0.016). Using VE/VCO(2)slope>34.2 as a cutoff value to predict patients with sPAP>50 mmHg (1 mmHg=0.133 kPa) yielded a sensitivity of 70.0% and a specificity of 64.3%. The degree of the linear correlation between VE/VCO(2)slope and sPAP is stronger in mild HF patients (peakVO(2)>14 ml.kg( 1).min(-1), r=0.686, P<0.001). Using VE/VCO(2) slope>34.2 as a cutoff value to predict sPAP>50 mmHg in mild HF patients, the sensitivity is 71.4% and the specificity is 93.8%. CONCLUSION: There is a significant linear correlation between VE/VCO(2)slope and sPAP in HF patients. VE/VCO(2)slope>34.2 is linked with a high possibility of sPAP>50 mmHg in HF patients, especially for patients with mild HF. Invasive hemodynamic examination and impact of special therapy are warranted in future studies to veryfy present results. PMID- 26888836 TI - [Recovery and relapse of left ventricular systolic dysfunction in hospitalized patients with dilated cardiomyopathy: frequency and related factors]. AB - OBJECTIVE: To investigate the frequency and predictors of recovery and relapse of left ventricular systolic dysfunction (LVSD) in hospitalized patients with dilated cardiomyopathy (DCM). METHODS: Patients with DCM hospitalized in Fuwai Hospital from October 2008 to December 2013 with repeat echocardiography results after discharge were reviewed and followed to December 2014 or until all-cause death or cardiac transplantation. Rate of recovery of LVSD, defined as an absolute increase in left ventricular ejection fraction (LVEF) of >10% to a level of >50% on follow-up, and those with relapse of LVSD, defined as a decrease in LVEF to a level of <45% after initial recovery was obtained and related factors affecting LVSD recovery and relapse were analyzed. RESULTS: After a mean follow up of (28 +/- 17) months, recovery of LVSD was evidenced in 114 of 382 patients (29.8%), LVEF increased from (31.6 +/- 6.0) % to (55.8 +/- 3.7) % (P<0.01) and left ventricular end-diastolic diameter (LVEDD) decreased from (65.1 +/- 6.7) mm to (53.5 +/- 4.9) mm (P<0.01) in these patients. Multiple logistic regression analysis showed that symptom duration of heart failure (OR=0.986, P<0.01), systolic blood pressure (SBP) (OR=1.026, P<0.01), LVEDD (OR=0.938, P<0.01) and LVEF (OR=1.038, P<0.05) at admission were independent predictors of LVSD recovery. During the subsequent follow-up of (24 +/-1 3) months after initial recovery, 17 of 88 patients (19.3%) suffered a relapse of LVSD, LVEF decreased from (54.3 +/- 2.6) % to (36.6 +/- 5.1) % (P<0.01), LVEDD increased from (57.5 +/ 4 .2) mm to (62.8 +/- 6.8) mm (P<0.01) in these patients. Multiple logistic regression analysis showed that less decrease in LVEDD at initial recovery of LVSD was independent predictor of LVSD relapse. CONCLUSIONS: About 30% hospitalized patients with DCM experienced LVSD recovery in this patient cohort. Symptom duration of heart failure, SBP, LVEDD and LVEF on admission were predictors of LVSD recovery. Moreover, LVSD relapse was observed in around 20% patients after initial LVSD recovery and less decrease in LVEDD at initial recovery serves as an independent risk factor for LVSD relapse. PMID- 26888837 TI - [Effects of renal denervation on left atrial fibrosis in rats with isoproterenol induced chronic heart failure]. AB - OBJECTIVE: To investigate the effects of renal denervation (RDN) on left atrial fibrosis in rats with chronic heart failure. METHODS: Sixty healthy male Sprague Dawley rats were randomly assigned to control group (n=10, intraperitoneal injection with 5 mg/kg normal saline daily for 3 consecutive weeks), sham group (n=25) and RDN group (n=25). Rats in sham and RDN group were intraperitoneally injected with 5 mg/kg isoproterenol daily for 3 consecutive weeks. RDN and sham RDN procedure was implemented at week 5. The renal arteries and veins were not isolated and the nerves were left intact in sham group. The experiment ended at week 10. Cardiac function, diastolic interventricular septal thickness (IVSD) and left atrial dimension (LAD) were evaluated by echocardiography at baseline, week 5 and 10. The rats of all three groups were sacrificed at week 10 and the left atrial tissue was used for following analysis: fibrosis was detected by Masson staining, plasma BNP was measured by ELISA kit, the protein expression of AngII, TGF-beta1, MMP2 and collagen I was determined by Western blot. RESULTS: (1) Cardiac function: compared with control group, LVEF decreased (P<0.01), IVSD (P<0.01) and LAD (P<0.01) increased significantly in the sham and RDN group at week 5. Compared with sham group at week 10, LVEF and IVSD significantly improved (P<0.05) and LAD tended to be smaller (P>0.05) in RDN group. (2) The degree of left atrial tissue fibrosis: Masson staining (collagen volume fraction, CVF) showed significantly decreased fibrosis of left atrial tissue in RDN group compared with that in sham group (P<0.01). (3) Plasma BNP level: ELISA assay revealed that plasma BNP in sham group was significantly increased compared with that in control group (P<0.05) and was similar between RND group and control group at week 10. (4) Protein expression of AngII, TGF-beta1, MMP2 and collagen I in rats left atrial: Western blot analysis demonstrated that the expression of AngII, TGF-beta1, MMP2 and collagen I was significantly down-regulated in RDN group compared to sham group (all P<0.05) but still significantly higher than in control group (all P<0.05). CONCLUSIONS: RDN can effectively attenuate the left atrial fibrosis in rats with isoproterenol induced chronic heart failure. The attenuation of left atrial fibrosis by RDN in these rats may be attributed to improved cardiac function and downregulated pro-fibrogenic factors (AngII, TGF beta1, MMP2 and collagen I). PMID- 26888838 TI - [High incidence of sudden cardiac death in one family with type-3 long QT syndrome: molecular genetics and electrophysiology mechanism analysis]. AB - OBJECTIVES: We identified the long QT syndrome (LQTS) patients, and detected the potential risk of LQTS in family members by using genetic testing and electrophysiological analysis, which helped provide clinical evaluation and appropriate treatment. METHODS: Detailed clinical characteristics and familiar history were obtained from the whole family members of an idiopathic pediatric LQTS patient. Two hundred healthy subjects with the same ethnic background were recruited as controls. The entire coding sequences of three candidate genes including KCNQ1, KCNH2 and SCN5A were screened for mutations in the proband. The function of the mutation was then explored by whole-cell patch clamp techniques, and the genetic testing and risk assessment of the family members were performed. RESULTS: The proband was clinically preliminary diagnosed as LQTS by 12-lead electrocardiogram. On the third day of metoprolol intake (25 mg, bid), she died suddenly at lunch. One heterozygous missense mutation (SCN5A-V411M) was identified in this proband, but the mutation was absent in 200 healthy subjects. The electrophysiological analysis indicated that SCN5A-V411M significantly increased the peak current density ((230.8 +/- 27.6)pA/pF vs. (101.2 +/- 10.9)pA/pF, n=10, P<0.01) and the late sodium current ((156.6 +/- 13.6)pA/pF vs. (95.9 +/- 7.9)pA/pF, n=12, P<0.01) of sodium channel compared to wide type. The enhanced sodium channel activation with a negative shift in the peak I-V relationship was significantly higher by -50 mV than wide type (85.0%+/- 7.4% vs. 41.5% +/- 2.6%, P<0.01), while the steady-state inactivation curves remained unchanged. Additionally, mother and grandmother of the proband were the silent mutation carriers with no symptoms, who needed the appropriate clinical assessment and follow-up. The proband's twin sister and aunt died of sudden infant death syndrome. CONCLUSIONS: We firstly reported a heterozygote missense mutation (SCN5A-V411M) in this Chinese family. V411M induced "gain of function" of sodium channel and formed the basis of type-3 LQTS. Genetic testing could help to increase the diagnostic accuracy, and facilitate clinical assessment and appropriate therapy to prevent sudden cardiac death of individuals with SCN5A V411M mutation. PMID- 26888839 TI - [Radiofrequency ablation can reverse the abnormal circulating microRNA expression changes in patients with atrial fibrillation]. AB - OBJECTIVE: To observe the change of circulating microRNAs(miRNAs), regulatory mechanism in patients with atrial fibrillation (AF) before and after radiofrequency ablation (RFA). METHODS: From January 2011 to December 2013, peripheral blood samples were taken from 30 AF patients (10 paroxysmal, 10 persistent and 10 permanent AF) before and 3 months after RFA. The total RNA was extracted and hybridized with the miRNA chips, and the differential expression of miRNA and clustering analysis in whole genome were made with Volcano Plot and tMEV software respectively, and validated by real-time PCR. The target gene analysis of miRNAs was predicted through the Mirbase, Miranda and Targetscan databases. Results were compared with those from 10 healthy subjects (control group). RESULTS: Compared with control group, the expressions of 25 miRNAs were down-regulated before RFA and up-regulated after RFA in AF group, while other 40 miRNAs expression changed in the opposite way; among them, the expressions of 7 miRNAs including miR-199a-3p/miR-199b-3p were down- regulated >1.5-fold before RFA and up-regulated>100-fold after RFA; oppositely, 6 miRNAs including miR-BART8 3p were up-regulated>1.5-fold before RFA and down-regulated>10-fold after RFA. Interestingly, 6 miRNAs including miR-30b-5p, which were involved in AF-related electrical and structural remodeling, were down-regulated>5-fold before RFA, but up-regulated>50-fold after RFA. Four miRNAs including miR-377-5p, which were involved in the regulation of CACNA1C ICaL channel protein, were different before and after RFA. CONCLUSION: miRNAs regulate the occurrence and development of AF. RFA can change the expression of miRNAs in AF patients, which may be important for reversing the electrical and structural remodeling and maintaining sinus rhythm after RFA. miRNAs, such as miR-30b-5p, miR-377-5p and miR-199a-3p/miR-199b 3p etc., might become the target markers for early diagnosis and intervention of AF in future. PMID- 26888840 TI - [Concentration of plasma vascular endothelial growth factor and related factors in patients with unstable angina pectoris]. AB - OBJECTIVE: To observe plasma vascular endothelial growth factor(VEGF) levels and related factors in patients with unstable angina pectoris(UAP). METHODS: A total of 108 consecutive patients with chest pain hospitalized in our department from October to December 2014 were included. They were divided into UAP (n=78) and non CHD group (n=30) by the result of coronary angiography(CAG). Coronary artery lesion was assessed according to the Gensini score, serum lipids, homocysteine(Hcy) levels and other biochemical indicators were also determined. The peripheral arterial tonometry was evaluated by reactive hyperemia index(RHI) measured by Endo-PAT2000 Noninvasive Diagnostic System.The level of plasma VEGF was detected in patients with unstable angina pectoris. Multiple linear regression analysis was used to analyze the correlations between VEGF and various related factors. RESULTS: Percent of male gender, triglyceride (TG) and Hcy levels were significantly higher in UAP group than in no-CHD group(all P<0.05). VEGF values was significantly higher ((102.1 +/- 55.7)ng/L vs.(80.9 +/- 38.1)ng/L, P<0.05), while RHI was significantly lower (1.53 +/- 0.27 vs.1.65 +/- 0.32, P<0.05) in UAP group than in no-CHD group. Multiple linear regression analysis showed that VEGF value was significantly correlated with degree of coronary artery stenosis, Gensini score and RHI (beta=38.03, P<0.01; beta=0.51, P<0.01; beta=-69.30, P=0.03; respectively). CONCLUSION: VEGF levels are significantly increased in patients with unstable angina pectoris, and VEGF level is significantly associated with the degree of coronary artery stenosis, Gensini score and RHI. V EGF level might serve as a new biochemical indicator for coronary artery lesion in patients with UAP. PMID- 26888841 TI - [Value of intravascular ultrasound in the assessment of pulmonary vascular properties and mortality in patients with pulmonary artery hypertension associated with connective tissue diseases]. AB - OBJECTIVE: To investigate the value of intravascular ultrasound (IVUS) on assessing pulmonary vascular properties (PVPs) and its relationship with hemodynamics, and mortality rate in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD). METHODS: Patients (n=51) with highly suspected PAH-CTD were prospectively enrolled in our department between July 2011 and March 2014. All patients underwent right heart catheterization (RHC) and IVUS, and were divided into 3 groups: PAH-CTD (n=25), PAH due to other reasons (n=15), and non-PAH control group (n=11). Based on IVUS, PAH patients were divided into distal (n=22) and proximal (n=18) remodeling subtypes.A total of 408 pulmonary segments were detected by IVUS, and all patients were followed up to (19 +/- 10) months. RESULTS: IVUS evidenced higher mean wall thickness (MWT) ((0.30 +/- 0.02) mm and (0.33 +/- 0.02) mm vs. (0.21 +/ 0.02) mm) and percentage of MWT (WTP) ((13.62 +/- 0.59)% and (14.39 +/- 0.77)% vs. (9.57 +/- 0.97)%) values in PAH patients compared to control patients (all P<0.01). Pulmonary vascular mechanical properties (PVMPs) including compliance ((8.85 +/- 0.82) * 10(-2)mm(2)/mmHg(1 mmHg=0.133 kPa) and (6.28 +/- 0.65) * 10( 2)mm(2)/mmHg vs. (41.59 +/- 5.02) * 10(-2) mm(2)/mmHg, all P<0.01), distensibility ((0.83 +/- 0.09)%/mmHg and (0.55 +/- 0.06)%/mmHg vs. (3.16 +/- 0.38) %/mmHg, all P<0.01), elastic modulus ((169.25 +/- 15.10) mmHg and (253.00 +/- 22.11) mmHg vs.(43.78 +/- 4.27) mmHg, all P<0.01) and stiffness index beta (4.19 +/- 0.41 and 5.18 +/- 0.34 vs. 2.39 +/- 0.27, P<0.05 or 0.01) in PAH groups were all significantly worse than in control group (all P<0.01). An inverse exponential association was found between PVMPs and hemodynamics with R(2) ranging from 0.544 to 0.777 (P<0.001). PVMPs tended to be better in group PAH-CTD than in PAH group due to other reasons.Mortality rate was similar between the two PAH groups, while PAH with distal remodeling subtype was linked with significantly higher mortality rate than PAH with the proximal remodeling subtype (23 % vs. 0, HR=10.14, P<0.05). CONCLUSIONS: IVUS plays an important role in the assessment of PAH-CTD patients in terms of evaluating PVPs and predicting mortality rate. PAH patients have deteriorated PVPs, but PVMPs tended to be better in PAH-CTD than in PAH patients due to other reasons. The mortality rate was similar between PAH groups, while PAH patients with the distal remodeling subtype is linked with a higher mortality rate than PAH patients with the proximal remodeling subtype. PMID- 26888843 TI - [Culture effects of mouse induced pluripotent stem cells by three-dimensional films in vitro]. AB - OBJECTIVE: To observe the proliferation and differentiation capacities of mouse induced pluripotent stem cells (miPSCs) cultured in 3-hydroxybutyrate-co-3 hydroxyhexanoate(PHBHHx) three-dimensional films three-dimension films for the purpose of finding a suitable polymeric biomaterials for forming myocardial patches. METHODS: miPSCs were recovered, passaged, cultured and identified, then miPSCs divided into the experimental and control groups. MiPSCs in the experimental group were cultured with PHBHHx three-dimension films. MiPSCs in the control group were cultured with traditional culture dish. Stem cell culture medium or differential medium were added to miPSCs to detecte cell vitality by CCK-8 after 72 hours or to measure the cTnT expression of miPSCs through immunofluorescence or the cTnT expression quantity through flow cytometry after 15 days. RESULTS: Cell activity assay showed that the absorbance values were 0.836 +/- 0.038 in the experimental group, 0.312 +/- 0.004 in the control group (P<0.05). Scanning electron microscope (SEM) observation showed that miPSCs grew well on the PHBHHx dimensional films with normal shape. Immunofluorescence results demonstrated positive cTnT expression in both groups and flow cytometry measured cTnT expression was (60.32 +/- 1.76)% in the experimental group and (47.54 +/- 1.46)% in the control group (P<0.05). CONCLUSIONS: miPSCs can survive, proliferate and differentiate on PHBHHx dimensional films. miPSCs proliferation and differentiation capacities are significantly higher in PHBHHx three dimensional films culture compared with the traditional cell culture. PMID- 26888844 TI - [The relationship between changes in ideal cardiovascular health score and the carotid intima-media thickness among the middle age and elderly population]. AB - OBJECTIVE: To explore the relationship between changes in ideal cardiovascular health score(DeltaICHS) and the carotid intima-media thickness(CIMT) among the middle age and elderly population. METHODS: A total of 5 852 cases were enrolled from 101 510 Kailuan Group employees who participated in the health examination in 2006-2007 and 2010-2011 through stratified random sampling. A total of 5 440 individuals met the inclusion criteria (>=40 years old; no history of stroke, transient ischemic attack, or myocardial infarction). CIMT was measured by ultrasound during 2010-2011 examination. Excluding individuals with incomplete data, 4 367 cases were included for the final analysis. According to the AHA definition of ideal cardiovascular health metric, individual DeltaICHS was evaluated and the subjects were divided into 3 groups: group reduced (DeltaICHS<0, n=1 355), invariant group (DeltaICHS=0, n=1 451) and elevated group (DeltaICHS>0, n=1 561). DeltaICHS was derived from the difference between 2010 2011 and 2006-2007. Multivariate linear regression and logistic regression analysis were used to analysis the relationship between DeltaICHS and CIMT. RESULTS: The ICHS was 3.03 +/- 1.27 in 2006-2007 study population and 3.09 +/- 1.40 (P<0.01) in 2010-2011 study population. Multivariate linear regression analysis showed that DeltaICHS was inversely related to CIMT. For every 1 score increase in DeltaICHS, CIMT decreased by 0.009 mm(B=-0.009, P<0.01). Multivariate logistic regression analysis showed that after adjusting for multiple confounding factors, the risk of CIMT wall thickening was lower in the DeltaICHS invariant group (OR=0.73, 95%CI: 0.59-0.91) and in DeltaICHS elevated group(OR=0.66, 95%CI: 0.52-0.82) compared to the DeltaICHS reduce group. CONCLUSION: Elevated DeltaICHS is an independent protective factors of CIMT increase in the middle age and elderly population. PMID- 26888845 TI - [Relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city]. AB - OBJECTIVE: To observe the relationship between alcohol dependence and new detected hypertension in adult residents of Xuzhou city. METHODS: Participants were sampled by stratified multi-stage randomly cluster sampling method from February 2013 to June 2013 among permanent residents aged 18 and more in Xuzhou city. The alcohol dependence was defined with Michigan Alcoholism Screening Test (MAST). Other information was obtained by questionnaire. Spearman correlation analysis and multivariate logistic regression analysis were performed to identify the relationship between alcohol dependence and new detected hypertension. RESULTS: The alcohol dependence rate was 11.56% on the whole cohort (n=36 157), and 22.02%(3 854/17 501) for male and 1.74%(324/18 656) for female(P<0.01). The new detected hypertension rate was 9.46%(3 422/36 157) in the whole cohort. The new detected hypertension rate increased in proportion with the severity of alcohol dependence (P<0.01). Spearman correlation analysis showed that alcohol dependence was positively correlated with systemic blood pressure(r=0.071, P<0.01) and diastolic blood pressure (r=0.077, P<0.01). After adjusting for gender, age, marital status, body mass index, smoking status, physical activity level, educational level, income level and region, multivariate logistic regression analysis showed that alcohol dependence was an independent risk factor for hypertension (low alcohol dependence: OR=1.44, 95%CI 1.14-1.81, P<0.01; light alcohol dependence: OR=1.35, 95%CI 1.11-1.64, P<0.01; medium alcohol dependence: OR=1.83, 95%CI 1.40-2.41, P<0.01). CONCLUSIONS: The alcohol dependence is an independent risk factor for new detected hypertension in adult residents of Xuzhou city. Intensive hypertension prevention and treatment strategies should be performed on this population based on our results. PMID- 26888842 TI - [Clinicopathological characteristics of aortic aneurysm in elderly patients]. AB - OBJECTIVE: To explore the prevalence and clinicopathological features of aortic aneurysm (AA) in elderly inpatients at autopsy. METHODS: All the AA cases were retrospectively analyzed in 909 autopsy cases aged 60-100 years in our hospital. The pathological changes, comorbidities and death reasons were evaluated. RESULTS: AA was diagnosed pathologically in 59 patients (6.5%), clinical diagnosis was not made in 37(62.7%) cases. The AA prevalence in patients aged >= 80 years was significantly higher than patients <80 years (10.2% vs. 2.9%, chi(2)=19.97, P<0.01). Abdominal AA was more common (91.5%) and the prevalence of multiple AA was 20.3%. Coronary artery disease (CAD) was diagnosed in 44 AA patients (74.6%) including 21(35.6%) with severe coronary artery stenosis and 7(11.9%) with three-vessel disease, 31 patients (52.5%) died of cardiac-cerebral diseases, including 7(11.9%) with ruptured AA. CONCLUSIONS: The prevalence of AA was high in elderly inpatients aged >=80 years with a relatively high missed diagnosis rate. AA was often complicated with CAD. The main cause of death of AA patients was cardiac-cerebral diseases. The screening, evaluation and treatment of AA should be enhanced in elderly patients, especially in patients aged 80 years and over. PMID- 26888846 TI - [Epidemiological survey on hypertension among Tibetan monks in Gannan Tibetan Autonomous Prefecture of Gansu Province]. AB - OBJECTIVE: To explore the prevalence, awareness, treatment and control rates of hypertension among Tibetan monks in Gannan Tibetan Autonomous Prefecture of Gansu Province, and to analyze risk factors of hypertension in this population. METHODS: A total of 984 (aged 18 and over) Tibetan monks in Gannan Tibetan Autonomous Prefecture of Gansu Province were included with cluster sampling method from March to June, 2014. General information was obtained by questionnaire and blood pressure was measured. Multivariate logistic regression analysis was applied to analyze the risk factors of blood pressure. RESULTS: Prevalence of hypertension in this population was 19.3% (190/984), and standardized prevalence rate was 21.7%. The prevalence of hypertension were 16.3% (82/502), 21.0% (60/286) and 24.5% (48/196), and standardized prevalence rate was 17.8%, 22.1% and 26.6% among Tibetan monks aged 18-39, 40-59 and >=60 years, respectively. Rates of awareness, treatment and control of hypertension in Tibetan monks were 9.5% (18/984), 4.2% (8/984)and 1.6% (3/984), respectively. Multivariate logistic regression analysis showed that age, body mass index and family history of hypertension were independent risk factors of hypertension in this population (P<0.01 or 0.05). CONCLUSIONS: Prevalence, awareness, treatment and control rates of hypertension among Tibetan monks in Gannan Tibetan Autonomous Prefecture of Gansu Province are relatively low. Age, body mass index and family history of hypertension are risk factors of hypertension in this population. PMID- 26888847 TI - [Association between heat wave and stroke mortality in Jiang'an District of Wuhan, China during 2003 to 2010: a time-series analysis]. AB - OBJECTIVE: To assess the association between heat wave and stroke mortality in Jiang'an District of Wuhan, China during 2003 to 2010. METHODS: Daily data of stroke mortality, meteorological factor and ambient pollution were collected from June to September during 2003 to 2010 in Jiang'an District of Wuhan.Quasi-Poisson regression in generalized additive model was applied to evaluate the impact of heat wave on stroke mortality on different lag days. RESULTS: During the study period, a total of 38 heat wave events and 191 heat wave days were registered. The total stroke death was 2 455 (1 182 women and 1 998 people aged 65 years old and over). Quasi-Poisson regression in generalized additive model showed that after controlling for long-term trend and seasonal trend, weekday, holiday, and relative humidity, heat wave was associated with stroke mortality on current day with relative risk of 1.15 (95%CI 1.01-1.30). Heat wave was not significantly associated with stroke mortality on current day among men (RR= 0.98, 95%CI 0.82 1.18, P=0.848) and people aged below 65 years old (RR=0.90, 95%CI 0.67-1.22, P=0.500), but relative risk increased to 1.34 (95%CI 1.12-1.62, P=0.002) and 1.20 (95%CI 1.04-1.39, P=0.002) for women and elderly (>=65 years old) people, respectively. When ambient pollutants (PM(10), sulfur dioxide and nitrogen dioxide) were involved into the models, the impacts of heat wave on stroke mortality almost remained unchanged. Lagged effects were found in the association between heat wave and stroke mortality, relative risks reached the highest on lag of 2 days and the effects of heat wave usually lasted for 3 to 5 days. Moreover, lagged patterns of the effects of heat wave on stroke mortality were different between female and male and people of different age groups.significantly increased relative risks were found on current day in the elderly (>=65 years old) people and women, while significant associations occurred on lag of 2 days for men and people aged below 65 years old. CONCLUSIONS: Heat wave increased the risk of stroke mortality in Jiang'an District of Wuhan. The effect of heat wave lasted for several days and lagged patterns of the effects of heat wave on stroke mortality were different between females and males and people of different age groups. PMID- 26888848 TI - [Treatment of acute myocardial infarction complicated with cardiac shock by primary percutaneous coronary intervention with the assistance of extracorporeal membrane oxygenation: a case report]. PMID- 26888849 TI - [One case of third-degree atrioventricular block post transcatheter aortic valve implantation]. PMID- 26888850 TI - [Clinical value of nutritional assessment in patients with chronic heart failure]. PMID- 26888851 TI - [Research update on IgG4-related cardiovascular disorders]. PMID- 26888852 TI - Performance of Gout Impact Scale in a longitudinal observational study of patients with gout. AB - OBJECTIVE: The aim was to evaluate the reliability, validity and responsiveness to change of the Gout Impact Scale (GIS), a disease-specific measure of patient reported outcomes, in a multicentre longitudinal prospective cohort of gout patients. METHODS: Subjects completed the GIS, a 24-item instrument with five scales: Concern Overall, Medication Side Effects, Unmet Treatment Need, Well Being during Attack, and Concern Over Attack. The total GIS score was calculated by averaging the GIS scale scores. HAQ-Disability Index (HAQ-DI), Short Form (SF) 36 physical and mental component summaries (PCS and MCS) and physician and patient gout severity assessments were also completed. Reliability was assessed with Cronbach's alpha. Baseline GIS scores were compared in subjects with and without gout attacks in the past 3 months using Wilcoxon rank sum tests. Multivariate linear regression was used to evaluate predictors of total GIS. Pearson's correlation coefficients 0.24-0.36 were considered moderate and >0.37 considered large. The effect size for responsiveness to change was interpreted as follows: 0.20-0.49 small, 0.50-0.79 medium and >0.79 large. RESULTS: In 147 subjects, reliability was acceptable for total GIS (0.93) and all GIS scales (0.82-0.94) except Medication Side Effects and Unmet Treatment Need. Total GIS and all scales except Medication Side Effects discriminated between subjects with and without recent gout attacks (P < 0.05). Total GIS showed moderate-to-large correlations with HAQ-DI, SF-36 PCS and MCS (0.33-0.46). Improvement in total GIS tracked with improved physician and patient severity scores. Worsening physician severity score and recent gout attack predicted worsening total GIS. CONCLUSION: Total GIS score is reliable, valid and responsive to change in patients with gout, and differentiates between subjects with and without recent gout attacks. PMID- 26888853 TI - Predictors of disease relapse in IgG4-related disease following rituximab. AB - OBJECTIVE: IgG4-related disease (IgG4-RD) is a relapsing-remitting condition responsible for fibroinflammatory lesions that can lead to organ damage and life threatening complications at nearly any anatomical site. The duration of remission following treatment varies and predictors of relapse are unclear. The objectives of this study were to review our experience with rituximab as remission induction in IgG4-RD, to clarify the duration of efficacy and to identify predictors of flare following treatment. METHODS: In this retrospective cohort study, all patients were treated with two doses of rituximab (1 g) separated by 15 days. Clinical, radiographic and laboratory data pertaining to rituximab response and disease relapse were collected from the electronic medical record. Kaplan-Meier curves were constructed to estimate the time to disease relapse. Log-rank analyses were performed to compare times to relapse among subgroups. Potential relapse predictors were evaluated with Cox regression analysis. RESULTS: Fifty-seven of 60 patients (95%) had clinical responses to rituximab. Forty-one patients (68%) were treated without glucocorticoids. Twenty one patients (37%) experienced relapses following treatment at a median time from the first infusion of 244 days. Baseline concentrations of serum IgG4, IgE and circulating eosinophils predicted subsequent relapses, with hazard ratios of 6.2 (95% CI: 1.2, 32.0), 8.2 (95% CI: 1.4, 50.0) and 7.9 (95% CI: 1.8, 34.7), respectively. The higher the baseline values, the greater the risk of relapse and the shorter the time to relapse. Only 10% of the patients had elevations of all three major risk factors, underscoring the importance of measuring all three at baseline. CONCLUSION: Baseline elevations in serum IgG4, IgE and blood eosinophil concentrations all predict IgG4-RD relapses independently. PMID- 26888854 TI - Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. AB - OBJECTIVES: To determine the longitudinal trends in serum levels of four myositis associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 gamma (TIF1-gamma), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs). METHODS: Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-gamma (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models. RESULTS: Following rituximab, anti-Jo-1 levels decreased over time (P < 0.001) and strongly correlated with all CSMs (P < 0.008). Anti-TIF1-gamma levels also decreased over time (P < 0.001) and were only associated with HAQ, MMT and physician and patient global disease activity. Anti-SRP levels did not change significantly over time, but were significantly associated with serum muscle enzymes. Anti-Mi-2 levels significantly decreased over time and were associated with muscle enzymes, MMT and the physician global score. CONCLUSION: Anti-Jo-1, anti-TIF1-gamma and anti Mi-2 levels in myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity. PMID- 26888856 TI - To Eat or Not to Eat: A Commentary on Eating Issues That Affect Home Parenteral Nutrition and Home Enteral Nutrition Consumers. PMID- 26888855 TI - Comparison Between Premixed and Compounded Parenteral Nutrition Solutions in Hospitalized Patients Requiring Parenteral Nutrition. AB - RATIONALE: Parenteral nutrition (PN) may be provided through compounded or premixed solutions. OBJECTIVE: To determine the proportion of stable custom compounded PN prescriptions that would fit within a 20% deviance of an existing premixed PN solution. METHODS: A retrospective study design was used. Inpatients who received PN in non-critical care units in the preceding year were screened for eligibility. Results are reported descriptively as means (95% confidence intervals) and proportions. RESULTS: We reviewed 97 PN prescriptions that met inclusion criteria. Stable hospital PN prescriptions compared with the reference premixed prescription provided 1838 (1777-1898) vs 1843 (1781-1905) kcal/d, P = .43; dextrose, 266 (254-277) vs 225 (216-234) g/d, P < .001; amino acids, 100 (95.9-104) vs 95.2 (91.7-98.7) g/d, P < .001; and lipids, 53.2 (51.3-55.1) vs 76.5 (73.8-79.2) g/d, P < .001. Fifty-eight of 97 (59.8%) matched for 2 of 3 macronutrients. Hospital compared with premixed lipid was lower 53.6 (43-64.2) g/d vs 75.5 (60.5-90.5) g/d, P < .001. Electrolytes differed between hospital and premixed solutions: sodium, 98.6 (95.0-102) vs 66.9 (64.6-69.9) mmol/L, P < .001; potassium, 93.7 (89.0-98.3) vs 57.4 (55.4-59.4) mmol/L, P < .001; and magnesium, 5.4 (4.8-5.4) vs 7.6 (7.4-7.9) mmol/L. CONCLUSIONS: Calories and protein were remarkably similar, but dextrose, lipid, and electrolytes differed between hospital PN and the reference premixed prescription. We believe that there may be a role for premixed solutions in quaternary centers in stable non-critically ill patients. PMID- 26888857 TI - Effects of Posture and Body Mass Index on Body Girth Assessment. AB - BACKGROUND: The present study aimed to evaluate the effect of posture on body girth assessment among hospitalized adults and older adults. We further explored the influence of body mass index (BMI) on this effect. MATERIALS AND METHODS: A cross-sectional study was conducted among hospitalized adult patients. Arm, waist, hip, and calf girths were obtained for each patient in standing and supine positions. Body girths were obtained in the 2 body positions, and differences were compared according to BMI normal-weight and overweight categories. RESULTS: In total, 123 patients (27.6% aged >=65 years) composed the study sample. Significant differences were found between measurements obtained in standing and supine positions, ranging from 0.6-1.1 cm. Intraclass correlation coefficient (ICC) values were >=0.97, and agreement ranged from 81.3%-87% (weighted kappa >= 0.84). Similar results were found when differences were stratified by BMI categories. CONCLUSION: Although body girth assessment in standing and supine positions in hospitalized adults and older adults differs, these differences are small and are not dependent on BMI categories. PMID- 26888858 TI - Incorporating Palliative Care Concepts Into Nutrition Practice: Across the Age Spectrum. AB - A practice gap exists between published guidelines and recommendations and actual clinical practice with life-sustaining treatments not always being based on the patient's wishes, including the provision of nutrition support therapies. Closing this gap requires an interdisciplinary approach that can be enhanced by incorporating basic palliative care concepts into nutrition support practice. In the fast-paced process of providing timely and effective medical treatments, communication often suffers and decision making is not always reflective of the patient's quality-of-life goals. The current healthcare clinical ethics model does not yet include optimum use of advance directives and early communication between patients and family members and their healthcare providers about treatment choices, including nutrition support. A collaborative, proactive, integrated process in all healthcare facilities and across levels of care and age groups, together with measurable sustained outcomes, shared best practices, and preventive ethics, will be needed to change the culture of care. Implementation of a better process, including basic palliative care concepts, requires improved communication skills by healthcare professionals. Formalized palliative care consults are warranted early in complex cases. An education technique, as presented in this article, of how clinicians can engage in critical and crucial conversations early with patients and family members, by incorporating the patient's values and cultural and religious diversity in easily understood language, is identified as an innovative tool. PMID- 26888860 TI - Involve clinicians to avert a digital disaster. PMID- 26888859 TI - Minimum Time to Achieve the Steady State and Optimum Abbreviated Period to Estimate the Resting Energy Expenditure by Indirect Calorimetry in Healthy Young Adults. AB - BACKGROUND: The optimum abbreviated period for measurement by indirect calorimetry (IC) to estimate the resting energy expenditure (REE), including the acclimation period, in healthy individuals has not been established. This study aimed to determine the acclimation time required to achieve the REE steady state during a 30-minute IC measurement and to define the optimum abbreviated measurement period in the steady state to estimate the REE in healthy young adults. METHODS: Thirty-nine volunteers (27 men and 12 women; age, 18-31 years) were recruited. The REE was obtained by IC over 30 minutes. Friedman's test was used to compare the coefficient of variation (CV%) among all 5-minute intervals (REE5). To compare the REE values obtained during the first REE5 interval in the steady state with the REE average values of the subsequent measurements, Student paired t test, linear regression, and Bland-Altman test were used. RESULTS: The CV% of the first REE5 (mean +/- standard deviation: 19.9% +/- 13.2%) was significantly higher (P < .0001) than that of all other REE5 (second REE5: 7.4% +/- 3.8%; third: 7.8% +/- 5.2%; fourth: 7.1% +/- 3.9%; fifth: 8.0% +/- 5.7%; sixth: 8.0% +/- 4.5%). No significant difference was found between the second REE5 and the REE average values of the last 20 minutes. The second REE5 explained 90% of the REE average of the last 20 minutes, with the 95% limits of agreement by the Bland-Altman test ranging from -142.92 to 150.44 kcal/d. CONCLUSION: Ten minutes can be used as an abbreviated alternative for IC measurements in healthy young adults, and values of the first 5-minute interval should be discarded. PMID- 26888861 TI - Cryoablation-induced phrenic nerve dysfunction with preserved inspiratory function of the diaphragm. PMID- 26888862 TI - Younger Onset Dementia. AB - This literature review focused on the experience, care, and service requirements of people with younger onset dementia. Systematic searches of 10 relevant bibliographic databases and a rigorous examination of the literature from nonacademic sources were undertaken. Searches identified 304 articles assessed for relevance and level of evidence, of which 74% were academic literature. The review identified the need for (1) more timely and accurate diagnosis and increased support immediately following diagnosis; (2) more individually tailored services addressing life cycle issues; (3) examination of the service needs of those living alone; (4) more systematic evaluation of services and programs; (5) further examination of service utilization, costs of illness, and cost effectiveness; and (6) current Australian clinical surveys to estimate prevalence, incidence, and survival rates. Although previous research has identified important service issues, there is a need for further studies with stronger research designs and consideration of the control of potentially confounding factors. PMID- 26888863 TI - Depression in the Family of Patients With Dementia in Korea. AB - INTRODUCTION: Dementia is the leading cause of disability worldwide in the elderly individuals. Although prior studies have examined psychiatric symptoms in dementia caregivers, few studies have examined physician-diagnosed depression in the family caregiver of a patient with dementia. METHODS: We used data from 457 864 respondents from the Korea Community Health Survey. We used logistic regression to examine the relationship between physician-diagnosed depression and cohabitation with a patient with dementia. RESULTS: Cohabitation with a patient with dementia (1.2% of the Korean population) was significantly associated with physician-diagnosed depression. The significance remained in females when the data were stratified by sex. A significant association also occurred among males with low family income. CONCLUSION: To reduce the burden of dementia, we need a management policy that includes the caregiver as well as the patient with dementia. In particular, political management for the vulnerable population, male caregiver in low-income family and female caregiver in high-income family, should be prepared. PMID- 26888864 TI - Retinal Nerve Fiber Layer Thinning in Alzheimer's Disease: A Case-Control Study in Comparison to Normal Aging, Parkinson's Disease, and Non-Alzheimer's Dementia. AB - Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and macular volume (MV) utilizing spectral domain optical coherence tomography (SD-OCT) were compared among patients with Alzheimer's disease (AD) dementia, non Alzheimer's disease (non-AD) dementia, amnestic mild cognitive impairment (aMCI), Parkinson's disease (PD), and age- and sex-matched controls in a cross-sectional cohort study. A total of 116 participants were diagnosed and evaluated (21 AD, 20 aMCI, 20 non-AD, 20 PD, and 34 controls) after comprehensive neurological, neuropsychology, and magnetic resonance imaging (MRI) volumetric evaluations. Retinal nerve fiber layer thickness, GCL thickness, and MV were measured. Analysis of variance models were used to compare groups on MRI volumetric measures, cognitive test results, and SD-OCT measures. Associations between SD OCT measures and other measures were performed using mixed-effect models. Spectral domain optical coherence tomography analysis of retinal markers, including RNFL thickness, GCL thickness, and MV, did not differ between amnestic MCI, AD dementia, PD, non-AD, dementia, and age- and sex-matched controls in a well-characterized patient cohort. PMID- 26888865 TI - Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment. AB - It has been established that COX-2 and downstream signaling by prostaglandin E2 (PGE2) play a key role in tumorigenesis through generation of inflammatory microenvironment. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) also regulates inflammatory responses in tumors. However, the relationship between these distinct pathways in tumorigenesis is not yet fully understood. We herein investigated the role of MyD88 in gastric tumorigenesis using Gan mice, which develop inflammation associated gastric tumors due to the simultaneous activation of the COX-2/PGE2 pathway and Wnt signaling. Notably, the disruption of Myd88 in Gan mice resulted in the significant suppression of gastric tumorigenesis with the inhibition of inflammatory responses, even though COX-2/PGE2 pathway is constitutively activated. Moreover, Myd88 disruption in bone marrow-derived cells (BMDCs) in Gan mice also suppressed inflammation and tumorigenesis, indicating that MyD88 signaling in BMDCs regulates the inflammatory microenvironment. We also found that expression of Tlr2 and its coreceptor Cd14 was induced in tumor epithelial cells in Gan mice, which was suppressed by the disruption of Myd88. It has already been shown that TLR2/CD14 signaling is important for stemness of intestinal epithelial cells. These results indicate that MyD88 in BMDCs, together with COX-2/PGE2 pathway, plays an essential role in the generation of the inflammatory microenvironment, which may promote tumorigenesis through induction of TLR2/CD14 pathway in tumor epithelial cells. These results suggest that inhibition of TLR/MyD88 signaling together with COX-2/PGE2 pathway will be an effective preventive strategy for gastric cancer. PMID- 26888866 TI - Large-Scale Survey of Intraspecific Fitness and Cell Morphology Variation in a Protoploid Yeast Species. AB - It is now clear that the exploration of the genetic and phenotypic diversity of nonmodel species greatly improves our knowledge in biology. In this context, we recently launched a population genomic analysis of the protoploid yeast Lachancea kluyveri (formerly Saccharomyces kluyveri), highlighting a broad genetic diversity (pi = 17 * 10(-3)) compared to the yeast model organism, S. cerevisiae (pi = 4 * 10(-3)). Here, we sought to generate a comprehensive view of the phenotypic diversity in this species. In total, 27 natural L. kluyveri isolates were subjected to trait profiling using the following independent approaches: (i) analyzing growth in 55 growth conditions and (ii) investigating 501 morphological changes at the cellular level. Despite higher genetic diversity, the fitness variance observed in L. kluyveri is lower than that in S. cerevisiae However, morphological features show an opposite trend. In addition, there is no correlation between the origins (ecological or geographical) of the isolate and the phenotypic patterns, demonstrating that trait variation follows neither population history nor source environment in L. kluyveri Finally, pairwise comparisons between growth rate correlation and genetic diversity show a clear decrease in phenotypic variability linked to genome variation increase, whereas no such a trend was identified for morphological changes. Overall, this study reveals for the first time the phenotypic diversity of a distantly related species to S. cerevisiae Given its genetic properties, L. kluyveri might be useful in further linkage mapping analyses of complex traits, and could ultimately provide a better insight into the evolution of the genotype-phenotype relationship across yeast species. PMID- 26888868 TI - Genome-Based Selection and Characterization of Fusarium circinatum-Specific Sequences. AB - Fusarium circinatum is an important pathogen of pine trees and its management in the commercial forestry environment relies largely on early detection, particularly in seedling nurseries. The fact that the entire genome of this pathogen is available opens new avenues for the development of diagnostic tools for this fungus. In this study we identified open reading frames (ORFs) unique to F. circinatum and determined that they were specific to the pathogen. The ORF identification process involved bioinformatics-based screening of all the putative F. circinatum ORFs against public databases. This was followed by functional characterization of ORFs found to be unique to F. circinatum. We used PCR- and hybridization-based approaches to confirm the presence of selected unique genes in different strains of F. circinatum and their absence from other Fusarium species for which genome sequence data are not yet available. These included species that are closely related to F. circinatum as well as those that are commonly encountered in the forestry environment. Thirty-six ORFs were identified as potentially unique to F. circinatum. Nineteen of these encode proteins with known domains while the other 17 encode proteins of unknown function. The results of our PCR analyses and hybridization assays showed that three of the selected genes were present in all of the strains of F. circinatum tested and absent from the other Fusarium species screened. These data thus indicate that the selected genes are common and unique to F. circinatum. These genes thus could be good candidates for use in rapid, in-the-field diagnostic assays specific to F. circinatum. Our study further demonstrates how genome sequence information can be mined for the identification of new diagnostic markers for the detection of plant pathogens. PMID- 26888870 TI - Why do we think we know what we know? A metaknowledge analysis of the salt controversy. AB - BACKGROUND: Although several public health organizations have recommended population-wide reduction in salt intake, the evidence on the population benefits remains unclear. We conducted a metaknowledge analysis of the literature on salt intake and health outcomes. METHODS: We identified reports--primary studies, systematic reviews, guidelines and comments, letters or reviews--addressing the effect of sodium intake on cerebro-cardiovascular disease or mortality. We classified reports as supportive or contradictory of the hypothesis that salt reduction leads to population benefits, and constructed a network of citations connecting these reports. We tested for citation bias using an exponential random graph model. We also assessed the inclusion of primary studies in systematic reviews on the topic. RESULTS: We identified 269 reports (25% primary studies, 5% systematic reviews, 4% guidelines and 66% comments, letters, or reviews) from between 1978 and 2014. Of these, 54% were supportive of the hypothesis, 33% were contradictory and 13% were inconclusive. Reports were 1.51 [95% confidence interval (CI) 1.38 to 1.65] times more likely to cite reports that drew a similar conclusion, than to cite reports drawing a different conclusion. In all, 48 primary studies were selected for inclusion across 10 systematic reviews. If any given primary study was selected by a review, the probability that a further review would also have selected it was 27.0% (95% CI 20.3% to 33.7%). CONCLUSIONS: We documented a strong polarization of scientific reports on the link between sodium intake and health outcomes, and a pattern of uncertainty in systematic reviews about what should count as evidence. PMID- 26888867 TI - Mapping of Variable DNA Methylation Across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome. AB - DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Many studies have mapped DNA methylation changes associated with embryogenesis, cell differentiation, and cancer at a genome-wide scale. Our understanding of genome-wide DNA methylation changes in a developmental or disease-related context has been steadily growing. However, the investigation of which CpGs are variably methylated in different normal cell or tissue types is still limited. Here, we present an in-depth analysis of 54 single CpG-resolution DNA methylomes of normal human cell types by integrating high throughput sequencing-based methylation data. We found that the ratio of methylated to unmethylated CpGs is relatively constant regardless of cell type. However, which CpGs made up the unmethylated complement was cell-type specific. We categorized the 26,000,000 human autosomal CpGs based on their methylation levels across multiple cell types to identify variably methylated CpGs and found that 22.6% exhibited variable DNA methylation. These variably methylated CpGs formed 660,000 variably methylated regions (VMRs), encompassing 11% of the genome. By integrating a multitude of genomic data, we found that VMRs enrich for histone modifications indicative of enhancers, suggesting their role as regulatory elements marking cell type specificity. VMRs enriched for transcription factor binding sites in a tissue-dependent manner. Importantly, they enriched for GWAS variants, suggesting that VMRs could potentially be implicated in disease and complex traits. Taken together, our results highlight the link between CpG methylation variation, genetic variation, and disease risk for many human cell types. PMID- 26888871 TI - Commentary: Salt and the assault of opinion on evidence. PMID- 26888872 TI - Commentary: The salt wars described but not explained--an invited commentary on 'Why do we think we know what we know? A metaknowledge analysis of the salt controversy'. PMID- 26888869 TI - Microarray Analysis of Gene Expression in Saccharomyces cerevisiae kap108Delta Mutants upon Addition of Oxidative Stress. AB - Protein transport between the nucleus and cytoplasm of eukaryotic cells is tightly regulated, providing a mechanism for controlling intracellular localization of proteins, and regulating gene expression. In this study, we have investigated the importance of nucleocytoplasmic transport mediated by the karyopherin Kap108 in regulating cellular responses to oxidative stress in Saccharomyces cerevisiae We carried out microarray analyses on wild-type and kap108 mutant cells grown under normal conditions, shortly after introduction of oxidative stress, after 1 hr of oxidative stress, and 1 hr after oxidative stress was removed. We observe more than 500 genes that undergo a 40% or greater change in differential expression between wild-type and kap108Delta cells under at least one of these conditions. Genes undergoing changes in expression can be categorized in two general groups: 1) those that are differentially expressed between wild-type and kap108Delta cells, no matter the oxidative stress conditions; and 2) those that have patterns of response dependent upon both the absence of Kap108, and introduction or removal of oxidative stress. Gene ontology analysis reveals that, among the genes whose expression is reduced in the absence of Kap108 are those involved in stress response and intracellular transport, while those overexpressed are largely involved in mating and pheromone response. We also identified 25 clusters of genes that undergo similar patterns of change in gene expression when oxidative stresses are added and subsequently removed, including genes involved in stress response, oxidation-reduction processing, iron homeostasis, ascospore wall assembly, transmembrane transport, and cell fusion during mating. These data suggest that Kap108 is important for regulating expression of genes involved in a variety of specific cell functions. PMID- 26888873 TI - Commentary: Accepting what we don't know will lead to progress. PMID- 26888875 TI - Sharp spike in deaths in England and Wales needs investigating, says public health expert. PMID- 26888874 TI - Safety and Efficacy of Subcutaneous Parenteral Nutrition in Older Patients: A Prospective Randomized Multicenter Clinical Trial. AB - BACKGROUND: Many patients who cannot tolerate adequate enteral nutrition could benefit from parenteral nutrition support but fail to receive it due to difficult intravenous (IV) access. The objective of this study was to compare the safety and efficacy of subcutaneous (SC) administration of parenteral nutrition with the peripheral IV route. MATERIALS AND METHODS: This was a prospective randomized multicenter study of 121 older hospitalized patients. The primary outcome was the composite end point of major local side effects, defined as local edema, blistering, erythema, phlebitis, cellulitis, unbearable pain, or route failure requiring a switch in route. Secondary outcomes were nutrition parameters, biochemical parameters, clinical outcomes, and safety. RESULTS: The SC route (n = 59) was noninferior to the IV route (n = 61) for major local side effects. Major local side effects trended higher in the IV group ( P = .059). Local edema was more common in the SC group ( P < .05), while route failure was more common in the IV group ( P < .001). Nutrition and biochemical parameters, safety, and clinical outcomes were similar between groups. CONCLUSIONS: The SC route of nutrient administration was better tolerated than the peripheral IV route. SC administration of parenteral nutrition represents a safe alternative to IV nutrition. PMID- 26888878 TI - Survivorship of Meniscal Allograft Transplantation in an Athletic Patient Population. AB - BACKGROUND: There are limited data evaluating the clinical outcomes of meniscal allograft transplantation (MAT) in physically active cohorts. PURPOSE: To determine the survivorship, complication rates, and functional outcomes of MAT in an active military population. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All military patients undergoing MAT between 2007 and 2013 were identified from the Military Health System. Previous/concomitant procedures, perioperative complications, reoperation rate, revision, and initiation of medical discharge for persistent knee disability were recorded. Univariate analysis was performed to identify associations between patient-based and surgical variables on selected endpoints. RESULTS: A total of 230 MATs (227 patients; 228 knees) were identified; the mean patient age was 27.2 years (range, 18-46 years), and the cohort was predominately male (89%). Approximately half (51%) of the patients had undergone prior, nonmeniscal knee procedures. Medial MATs were performed in 160 (69%) cases, and isolated MATs were most common (60%). A total of 51 complications occurred in 46 (21.1%) patients, including a secondary tear or extrusion (9%). At a mean clinical follow-up of 2.14 years, 10 (4.4%) patients required secondary meniscal debridement, while 1 (0.4%) patient required revision MAT and 2 (0.9%) patients underwent total knee arthroplasty. After MAT, 50 (22%) patients underwent knee-related military discharge at a mean of 2.49 years postoperatively. Tobacco use (P = .028) was associated with significantly increased risk of failure, and operation by fellowship-trained surgeons trended toward significance as a protective factor (P = .078). Furthermore, high-volume surgeons (>=1 MAT/year; range, 9-35) had significantly reduced rates of failure (P = .046). CONCLUSION: While reporting low reoperation and revision rates, this investigation indicates that 22% of patients with MAT were unable to return to military duty due to persistent knee limitations at short-term follow-up. Increased surgical experience may decrease rates of failure after MAT. Careful patient selection and referral to subspecialty-trained, higher volume surgeons should be considered to optimize clinical outcomes after MAT. PMID- 26888876 TI - Subradiographic Foot and Ankle Fractures and Bone Contusions Detected by MRI in Elite Ice Hockey Players. AB - BACKGROUND: In ice hockey players, serious bone injuries in the foot and ankle, especially those attributed to impact from the moving puck, may be radiographically occult and underrecognized. PURPOSE/HYPOTHESIS: The purpose of this research was to study foot and ankle bone injuries detected with magnetic resonance imaging (MRI) that occurred in elite hockey players. The hypothesis was that these injuries predominate medially, especially when caused by the impact from the puck, and are associated with prolonged lost playing time. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Three independent observers, blinded to the mechanism of injury, retrospectively reviewed foot and ankle MRI examinations acquired after 31 acute injuries that occurred in 27 elite ice hockey players who had no radiographically visible fractures. Bone abnormalities were classified as fractures or varying degrees of contusion based on predetermined definitions. Interobserver agreement was analyzed with kappa statistics. The association between the injury mechanism and the bones involved was examined with the Fisher exact test. A t test was applied to determine if MRI evidence of a severe bone injury (defined as either a fracture or a high-grade bone contusion) was associated with longer recovery times, when return-to-play information was available. RESULTS: The observers identified at least 1 bone injury in 27 of the 31 MRI examinations, including 10 with radiographically occult fractures. Agreement among the 3 observers for injury categorization was substantial (kappa = 0.76). Seventeen injuries were caused by a direct blow (15 from a moving puck, 2 from an uncertain source), resulting in 6 fractures and 6 high-grade bone contusions, with 14 of the 17 involving a medial bone (medial malleolus, navicular, or first metatarsal base). Compared with other mechanisms, direct impaction was statistically more likely to result in a severe bone injury and to involve the medial foot and ankle. In 20 injuries where return-to-play information was available, players with severe bone injuries missed a mean of 10.6 games compared with 2.4 games for other players (P = .05). CONCLUSION: MRI can show severe bone injuries that are not visible radiographically in ice hockey players. Most fractures and high-grade contusions involve the medial ankle and midfoot bones, can be caused by direct blows from the puck, and are associated with prolonged recovery times. PMID- 26888877 TI - Participation in Pre-High School Football and Neurological, Neuroradiological, and Neuropsychological Findings in Later Life: A Study of 45 Retired National Football League Players. AB - BACKGROUND: A recent study found that an earlier age of first exposure (AFE) to tackle football was associated with long-term neurocognitive impairment in retired National Football League (NFL) players. PURPOSE: To assess the association between years of exposure to pre-high school football (PreYOE) and neuroradiological, neurological, and neuropsychological outcome measures in a different sample of retired NFL players. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Forty-five former NFL players were included in this study. All participants prospectively completed extensive history taking, a neurological examination, brain magnetic resonance imaging, and a comprehensive battery of neuropsychological tests. To measure the associations between PreYOE and these outcome measures, multiple regression models were utilized while controlling for several covariates. RESULTS: After applying a Bonferroni correction for multiple comparisons, none of the neurological, neuroradiological, or neuropsychological outcome measures yielded a significant relationship with PreYOE. A second Bonferroni-corrected analysis of a subset of these athletes with self-reported learning disability yielded no significant relationships on paper and-pencil neurocognitive tests but did result in a significant association between learning disability and computerized indices of visual motor speed and reaction time. CONCLUSION: The current study failed to replicate the results of a prior study, which concluded that an earlier AFE to tackle football might result in long-term neurocognitive deficits. In 45 retired NFL athletes, there were no associations between PreYOE and neuroradiological, neurological, and neuropsychological outcome measures. PMID- 26888879 TI - Influence of Bony Defects on Preoperative Shoulder Function in Recurrent Anteroinferior Shoulder Instability. AB - BACKGROUND: Recurrent anteroinferior shoulder dislocations are often associated with bony glenoid and humeral defects. The influence of those bony lesions on the postoperative outcomes after arthroscopic shoulder stabilization procedures has been the subject of many studies. Little is known about the influence of those lesions on preoperative function. PURPOSE: To evaluate the influence of glenoid and humeral bony defects on preoperative shoulder function in recurrent anteroinferior shoulder instability. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Included in the study were 90 patients (70 men, 20 women; mean age, 27.1 years; 24 patients with prior failed stabilization) with posttraumatic recurrent anteroinferior shoulder instability who underwent preoperative computed tomography (CT) of both shoulders. The glenoid index was used to measure glenoid defect on a 3-dimensional CT. Humeral head defect was measured on a 2-dimensional CT with evaluation of the Hill-Sachs quotient, product, sum, and difference. Preoperative evaluation also included the Rowe score, Constant score, Walch-Duplay score, Melbourne Instability Shoulder Score (MISS), Western Ontario Shoulder Instability Index (WOSI), and Subjective Shoulder Value (SSV). RESULTS: There was a weak but significant correlation of the Hill-Sachs quotient and the glenoid index with the Rowe score (P = .03, r = 0.22 and P = .03, r = 0.23, respectively). Furthermore, the Hill-Sachs product significantly correlated with the WOSI (P = .02); in particular, the physical symptoms subscore showed a significant correlation (P = .04). The glenoid index showed a significant correlation with the SSV (P < .01). No significant correlation was found between the Walch-Duplay score, Constant score, or MISS and bony defects. CONCLUSION: The results of this study show that objective and subjective scoring systems correlate significantly with the clinical condition of patients with recurrent shoulder instability and associated bony defects. It is recommended that clinicians use the Rowe score, WOSI, and SSV for the clinical evaluation of patients with recurrent anteroinferior shoulder instability and associated bony defects. These evaluation systems may provide an early clinical indication of bony defects. Furthermore, very poor results on these evaluations could underline the necessity of a CT scan for the diagnosis of bony defects in recurrent shoulder instability and might be helpful for decision making concerning the indication of a CT. PMID- 26888880 TI - Fasciotomy for Deep Posterior Compartment Syndrome in the Lower Leg: A Prospective Study. AB - BACKGROUND: Patients with exercise-induced lower leg pain may suffer from deep posterior chronic exertional compartment syndrome (dp-CECS). Current evidence for the efficacy of surgery is based on retrospective studies. Effects of fasciotomy on symptoms associated with dp-CECS have not been systematically studied, and reasons for unsuccessful surgery are unknown. PURPOSE: To report the short- and long-term effects of fasciotomy on pain, tightness, and cramps in a prospective cohort of patients with isolated dp-CECS. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2011 and January 2015, pain, tightness, cramps, muscle weakness, and diminished sensation were scored (5-item verbal rating scale ranging from very severe [5 points] to absent [1 point]) in patients with dp-CECS before and after fasciotomy. Outcomes were graded as excellent, good, moderate, fair, or poor. Fair and poor cases were again analyzed during a follow-up visit in the outpatient department. RESULTS: Forty-four patients underwent surgery for isolated dp-CECS. Short-term follow-up (median, 4 months; range, 3-7 months) was complete in 42 of the 44 patients (95%; median patient age, 23 years; 23 male; 64 operated legs). Long-term follow-up (median, 27 months; range, 12-42 months) was complete in 34 of 37 eligible patients (92%). Before surgery, exertional pain was very severe (27%) or severe (61%). Fasciotomy improved all symptoms, both in the short term (preoperative vs postoperative pain, 4.1 +/- 0.6 vs 2.3 +/- 1.1; P < .001) and the long term (pain, 4.2 +/- 0.6 vs 2.7 +/- 1.3; P < .001). Levels of tightness, cramps, muscle weakness, and diminished sensation demonstrated similar significant improvements. Short- and long-term symptom scores did not differ. The short-term outcome was excellent in 29%, good in 29%, moderate in 21%, fair in 12%, and poor in 10% of patients. In the long term, outcomes were similar (excellent, 12%; good, 35%; moderate, 24%; fair, 18%; and poor, 12%). An unsatisfactory outcome (fair or poor) was often caused by alternative types of CECS (eg, anterior or lateral CECS) or to medial tibial stress syndrome. Based on their outcome, 76% of patients would opt for surgery again. CONCLUSION: Fasciotomy was beneficial in 71% of patients with dp CECS in the lower leg; 47% of study patients experienced a good to excellent outcome. Outcomes were stable in the long term. Persistent complaints were often caused by other untreated conditions. PMID- 26888881 TI - Outcomes of the Remplissage Procedure and Its Effects on Return to Sports: Average 5-Year Follow-up. AB - BACKGROUND: Short-term outcomes for patients with large, engaging Hill-Sachs lesions who underwent remplissage have demonstrated good results. However, limited data are available for longer term outcomes. PURPOSE: To evaluate the long-term outcomes of remplissage and determine the long-term rate of return to specific sports postoperatively. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This was a retrospective review of patients treated with the remplissage procedure from 2007 to 2013. All underwent preoperative magnetic resonance imaging demonstrating large Hill-Sachs lesions by the Rowe criteria and glenoid bone loss <20%. All Hill-Sachs lesions were "off track" by an arthroscopic examination and preoperative imaging. At final follow-up, patients underwent a range of motion evaluation and were administered a detailed outcome survey, which included Western Ontario Shoulder Instability Index (WOSI) and American Shoulder and Elbow Surgeons (ASES) scores as well as questions regarding sports, employment, physical activities, and dislocation events. RESULTS: A total of 50 patients (51 shoulders) were included in the study. The average patient age at surgery was 29.8 years (range, 15.0-72.4 years), and the average follow-up time was 60.7 months (range, 25.5-97.6 months); 20.0% of patients underwent previous surgery on their shoulder. The average postoperative WOSI score was 79.5%, and the average ASES score was 89.3. Six shoulders had dislocation events (11.8%) postoperatively: 3 were traumatic, and 3 were atraumatic. Increased preoperative dislocations led to a greater risk of a postoperative dislocation (P < .001). There was also a trend toward higher postoperative dislocation rates in patients who underwent revision (P = .062). The average loss of external rotation was 5.26 degrees (P = .13). The rate of return to >=1 sports was 95.5% of patients at an average of 7.0 months postoperatively; 81.0% returned to their previous intensity and level of sport. Of patients who played a throwing sport, 65.5% (n = 19) stated that they had problems throwing, and 58.6% (n = 17) felt that they could not normally wind up throwing a ball. Direct rates of return to overhead sports were volleyball, 100%; basketball, 69%; baseball, 50%; and football, 50%. CONCLUSION: The redislocation rate after remplissage was 11.8% at an average of 5 years, with 95.5% of patients returning to full sports at an average of 7 months. For throwing sports, 65.5% of patients complained of decreased range of motion during throwing. The results should be considered preoperatively in candidates for remplissage who are engaged in throwing sports. PMID- 26888882 TI - Establishing and sustaining health observatories serving urbanized populations around the world: scoping study and survey. AB - BACKGROUND: The 'health observatory' model has successfully proliferated across several world regions, this study being conducted to define the geographical and physical bases and main functions of health observatories serving largely urbanized populations and the support needed for set-up and sustainability. METHODS: A scoping study of literature and observatory websites was undertaken to identify health observatories, main functions, year established and publications, followed by a self-completion survey to further investigate these characteristics, define the help observatories would have liked at set-up and later on, and how such help might effectively be accessed. RESULTS: Of 69 health observatories contacted, 27 (39%) mainly established since 2000 completed the survey. Most responding observatories had a sub-national/regional or sub regional/local geographical base and no one type of physical or organizational base predominated. Nearly all observatories undertook preparation of population based health reports and intelligence, data analysis and interpretation services, and a primary commitment to working with local/regional partners to support evidence-based decision-making. Most prioritized help with deciding and defining the scope of the observatory, estimating the core resources required for establishing/developing it, addressing sustainability issues, identifying knowledge, skills and skill-mix required to undertake the health intelligence/analytic functions, accessing data/IT expertise and developing training and capacity-building programmes. The preferred means of accessing this support was a virtual network(s) of experts on particular topics to support mutual learning and toolboxes developed for specific observatory functions. CONCLUSIONS: Although the health observatory as an organizational model is maturing, the learning derived from sharing structured guidance and support is regarded as invaluable. PMID- 26888883 TI - Unmet Needs of African Americans and Whites at the Time of Palliative Care Consultation. AB - CONTEXT: Differences among patient populations that present to consultative palliative care are not known. Such an appreciation would inform health-care delivery tailored to unique populations. OBJECTIVES: We aimed to compare characteristics and palliative care needs of African Americans (AAs) and whites during initial palliative care consultation. METHODS: We analyzed patient reported, clinician-entered clinical encounter data from a large, multisite community-based, nonhospice palliative care collaborative. We included first specialty palliative care consultations from January 1, 2014, to July 2, 2015, across 15 sites within the Global Palliative Care Quality Alliance registry. Demographics, disease, performance status, advance care planning, and symptom prevalence/severity were compared. RESULTS: Of 775 patients, 12.9% (N = 100) were AA. African Americans were younger (63 vs 75.4 years, P < .0001). A larger proportion of AAs had a diagnosis of cancer (45.0% vs 36.3%, P = .09) and in the hospital (71% vs 61.8%, P = .07). African Americans were more likely to have a Palliative Performance Score of 0 to 30 (35.6% vs 23.7%, P = .049). Around 50% in both racial groups were full code; slightly more than 40% had an advance directive. Nearly two-thirds in both racial groups reported 3 or more symptoms of any severity; one-third reported 3 or more moderate or severe symptoms. A larger proportion of Africans than whites reported pain of any severity (66.0% vs 56.1%, P = .06). CONCLUSION: All patients present to palliative care consultations with significant symptom and advance care planning needs. Further research is needed to identify how to deliver palliative care: earlier, in noncancer conditions, and improve pain management in AA populations. PMID- 26888885 TI - A Study of the Association Between Multidisciplinary Home Care and Home Death Among Thai Palliative Care Patients. AB - PURPOSE: Many terminally ill patients would prefer to stay and die in their own homes, but unfortunately, some may not be able to do so. Although there are many factors associated with successful home deaths, receiving palliative home visits from the multidisciplinary care teams is one of the key factors that enable patients to die at home. Our study was aimed to find whether there was any association between our palliative home care program and home death. METHODS: A retrospective study was conducted in the Department of Family Medicine at Ramathibodi Hospital between January 2012 and May 2014. All of the patients who were referred to multidisciplinary palliative care teams were included. The data set comprised of patient's profile, disease status, functional status, patient's symptoms, preferred place of death, frequency of home visits, types of team interventions, and patient's actual place of death. Multiple logistic regression was applied in order to determine the association between the variables and the probability of dying at home. RESULTS: A total of 142 patients were included into the study. At the end of the study, 50 (35.2%) patients died at home and 92 (64.8%) patients died in the hospital. The multivariate logistic regression analysis demonstrated a strong association between multidisciplinary home care and home death (odds ratio 6.57, 95% confidence interval [CI] 2.48-17.38). CONCLUSION: Palliative home care was a significant factor enabling patients who want to die at home. We encourage health policy makers to promote the development of community-based palliative care programs in Thailand. PMID- 26888886 TI - Measurement outcomes from hip simulators. AB - Simulation of wear in total hip replacements has been recognised as an important factor in determining the likelihood of clinical success. However, accurate measurement of wear can be problematic with factors such as number and morphology of wear particles produced as well as ion release proving more important in the biological response to hip replacements than wear volume or wear rate alone. In this study, hard-on-hard (CoCr alloy, AgCrN coating) and hard-on-soft (CoCr alloy and CrN coating on vitamin E blended highly cross-linked polyethylene) bearing combinations were tested in an orbital hip simulator under standard and some adverse conditions. Gravimetric wear rates were determined for all bearings, with cobalt and where applicable, silver release determined throughout testing. Isolation of wear particles from the lubricating fluid was used to determine the influence of different bearing combinations and wear conditions on particle morphology. It was found that cobalt and silver could be measured in the lubricating fluid even when volumetric wear was not detectable. In hard-on-hard bearings, Pearson's correlation of 0.98 was established between metal release into the lubricating fluid and wear volume. In hard-on-soft bearings, coating the head did not influence the polyethylene wear rates measured under standard conditions but did influence the cobalt release; the diameter influenced both polyethylene wear and cobalt release, and the introduction of adverse testing generated smaller polyethylene particles. While hip simulators can be useful to assess the wear performance of a new material or design, measurement of other outcomes may yield greater insight into the clinical behaviour of the bearings in vivo. PMID- 26888884 TI - Investigation of Optimal Time for Starting Betamethasone Using Fatigue Scores and Prognostic Nutritional Index in Terminally Ill Patients With Cancer-Related Fatigue. AB - BACKGROUND: Corticosteroids are frequently used to treat cancer-related fatigue (CRF), but it is yet to be established as standard care, and few reports have defined the appropriate time to start treatment. OBJECTIVES: We investigated the optimal time for starting betamethasone and evaluated the clinical validity of using the prognostic nutritional index (PNI) for this purpose. METHODS: Data were retrospectively collected for patients with terminal cancer receiving betamethasone for palliative care. Fatigue strength was evaluated by the daily occurrence of fatigue, using proportion of adequate fatigue, AF(%), defined as the average of the daily score for all treatment days, AF(%)all, the initial 5 days, AF(%)initi5, or the last 5 days, AF(%)last5. We examined (1) the relationship between survival time and adequate fatigue for CRF and (2) the correlation between survival time and PNI (based on serum albumin and lymphocytes). RESULTS: Data from 24 patients were included. The AF(%)all was approximately 50% at 42 days before death and gradually decreased as the survival time shortened ( R2 =.41, P <.001). There was a clear positive correlation between AF(%)all and AF(%)initi5 ( R2 =.84, P <.001). At 42 days before death, PNI was approximately 30 and significantly correlated with the survival time ( R2 = .873, P <.001). CONCLUSION: The adequate fatigue appears to be dependent on survival time, and PNI might be useful for identifying patients that will benefit from betamethasone use. It is hoped that these results will contribute to individualized pharmacotherapy of terminally ill patients with CRF. PMID- 26888887 TI - Acetabular shell deformation as a function of shell stiffness and bone strength. AB - Press-fit acetabular shells used for hip replacement rely upon an interference fit with the bone to provide initial stability. This process may result in deformation of the shell. This study aimed to model shell deformation as a process of shell stiffness and bone strength. A cohort of 32 shells with two different wall thicknesses (3 and 4 mm) and 10 different shell sizes (44- to 62 mm outer diameter) were implanted into eight cadavers. Shell deformation was then measured in the cadavers using a previously validated ATOS Triple Scan III optical system. The shell-bone interface was then considered as a spring system according to Hooke's law and from this the force exerted on the shell by the bone was calculated using a combined stiffness consisting of the measured shell stiffness and a calculated bone stiffness. The median radial stiffness for the 3 mm wall thickness was 4192 N/mm (range, 2920-6257 N/mm), while for the 4-mm wall thickness the median was 9633 N/mm (range, 6875-14,341 N/mm). The median deformation was 48 um (range, 3-187 um), while the median force was 256 N (range, 26-916 N). No statistically significant correlation was found between shell stiffness and deformation. Deformation was also found to be not fully symmetric (centres 180 degrees apart), with a median angle discrepancy of 11.5 degrees between the two maximum positive points of deformation. Further work is still required to understand how the bone influences acetabular shell deformation. PMID- 26888888 TI - The Australian Work Exposures Study: Prevalence of Occupational Exposure to Respirable Crystalline Silica. AB - BACKGROUND: Respirable crystalline silica (RCS) is a biologically active dust that can accumulate in the lung and induce silicosis and lung cancer. Despite occupational exposure being the predominant source, no study has described current occupational RCS exposure on a national scale in Australia. The aim of this study is to estimate the characteristics of those exposed and the circumstances of RCS exposure in Australian workplaces. METHODS: A cross sectional survey of the Australian working population (18-65 years old) was conducted. Information about the respondents' current job and their demographic characteristics was collected in a telephone interview. Occupational exposure to RCS was determined based on preprogrammed decision rules regarding potential levels of exposure associated with self-reported tasks. RESULTS: Overall, 6.4% of respondents were deemed exposed to RCS at work in 2012 (3.3% were exposed at a high level). The exposure varied with sex, state of residence, and socioeconomic status. Miners and construction workers were most likely to be highly exposed to RCS when performing tasks with concrete or cement or working near crushers that create RCS-containing dusts. When extrapolated to the entire Australian working population, 6.6% of Australian workers were exposed to RCS and 3.7% were highly exposed when carrying out tasks at work. CONCLUSION: This is the first study investigating occupational RCS exposure in an entire national working population. The information about occupational tasks that lead to high level RCS exposure provided by this study will inform the direction of occupational interventions and policies. PMID- 26888889 TI - Comparison of Multiple Measures of Noise Exposure in Paper Mills. AB - BACKGROUND: Noise exposures are associated with a host of adverse health effects, yet these exposures remain inadequately characterized in many industrial operations, including paper mills. We assessed noise at four paper mills using three measures: (i) personal noise dosimetry, (ii) area noise measurements, and (iii) questionnaire items addressing several different aspects of perceived noise exposure. METHODS: We assessed exposures to noise characterized using the three measures and compared the relationships between them. We also estimated the validity of each of the three measures using a novel application of the Method of Triads, which does not appear to have been used previously in the occupational health literature. RESULTS: We collected 209 valid dosimetry measurements and collected perceived noise exposure survey items from 170 workers, along with 100 area measurements. We identified exposures in excess of 85 dBA at all mills. The dosimetry and area noise measurements assigned to individual subjects generally showed good agreement, but for some operations within mill, large differences between the two measures were observed, and a substantial fraction of paired measures differed by >5 dB. Perceived noise exposures varied greatly between the mills, particularly for an item related to difficulty speaking in noise. One perceived noise exposure item related to difficulty hearing due to noise showed strong and significant correlations with both dosimetry and area measurements. The Method of Triads analysis showed that dosimetry measures had the highest estimated validity coefficient (0.70), and that the best performing perceived exposure measure had validity that exceeded that of area measurements (0.48 versus 0.40, respectively). CONCLUSIONS: Workers in Swedish pulp mills have the potential for exposures to high levels of noise. Our results suggest that, while dosimetry remains the preferred approach to exposure assessment, perceived noise exposures can be used to evaluate potential exposures to noise in epidemiological studies. PMID- 26888890 TI - Changes in fine-root production, phenology and spatial distribution in response to N application in irrigated sweet cherry trees. AB - Factors regulating fine-root growth are poorly understood, particularly in fruit tree species. In this context, the effects of N addition on the temporal and spatial distribution of fine-root growth and on the fine-root turnover were assessed in irrigated sweet cherry trees. The influence of other exogenous and endogenous factors was also examined. The rhizotron technique was used to measure the length-based fine-root growth in trees fertilized at two N rates (0 and 60 kg ha(-1)), and the above-ground growth, leaf net assimilation, and air and soil variables were simultaneously monitored. N fertilization exerted a basal effect throughout the season, changing the magnitude, temporal patterns and spatial distribution of fine-root production and mortality. Specifically, N addition enhanced the total fine-root production by increasing rates and extending the production period. On average, N-fertilized trees had a length-based production that was 110-180% higher than in control trees, depending on growing season. Mortality was proportional to production, but turnover rates were inconsistently affected. Root production and mortality was homogeneously distributed in the soil profile of N-fertilized trees while control trees had 70-80% of the total fine root production and mortality concentrated below 50 cm depth. Root mortality rates were associated with soil temperature and water content. In contrast, root production rates were primarily under endogenous control, specifically through source-sink relationships, which in turn were affected by N supply through changes in leaf photosynthetic level. Therefore, exogenous and endogenous factors interacted to control the fine-root dynamics of irrigated sweet cherry trees. PMID- 26888891 TI - Fast acclimation of freezing resistance suggests no influence of winter minimum temperature on the range limit of European beech. AB - Low temperature extremes drive species distribution at a global scale. Here, we assessed the acclimation potential of freezing resistance in European beech (Fagus sylvaticaL.) during winter. We specifically asked (i) how do beech populations growing in contrasting climates differ in their maximum freezing resistance, (ii) do differences result from genetic differentiation or phenotypic plasticity to preceding temperatures and (iii) is beech at risk of freezing damage in winter across its distribution range. We investigated the genetic and environmental components of freezing resistance in buds of adult beech trees from three different populations along a natural large temperature gradient in north western Switzerland, including the site holding the cold temperature record in Switzerland. Freezing resistance of leaf primordia in buds varied significantly among populations, with LT50values (lethal temperature for 50% of samples) ranging from -25 to -40 degrees C, correlating with midwinter temperatures of the site of origin. Cambial meristems and the pith of shoots showed high freezing resistance in all three populations, with only a trend to lower freezing resistance at the warmer site. After hardening samples at -6 degrees C for 5 days, freezing resistance of leaf primordia increased in all provenances by up to 4.5 K. After additional hardening at -15 degrees C for 3 days, all leaf primordia were freezing resistant to -40 degrees C. We demonstrate that freezing resistance ofF. sylvaticahas a high ability to acclimate to temperature changes in winter, whereas the genetic differentiation of freezing resistance among populations seems negligible over this small geographic scale but large climatic gradient. In contrast to the assumption made in most of the species distribution models, we suggest that absolute minimum temperature in winter is unlikely to shape the cold range limit of beech. We conclude that the rapid acclimation of freezing resistance to winter temperatures allows beech to track changing climatic conditions, especially during unusually warm winters interrupted by very cold weather. PMID- 26888892 TI - Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial. AB - BACKGROUND: The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS: We developed a case-cohort study within the Prevencion con Dieta Mediterranea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS: After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05-2.76) and 2.09 (1.27-3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS: Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke. PMID- 26888893 TI - Minimizing Matrix Effects for the Accurate Quantification of 25-Hydroxyvitamin D Metabolites in Dried Blood Spots by LC-MS/MS. AB - BACKGROUND: The noncalcemic actions of vitamin D in multiple organs are now widely recognized. Vitamin D status has been linked with a wide variety of conditions, which has led to an increasing demand for vitamin D screening. In particular, there is intense interest in the impact of vitamin D on a variety of developmental conditions. The most readily accessible pediatric samples are dried blood spots, and health organizations are increasingly archiving such samples for later assessment of the antecedents of disease. METHODS: In 2009, we developed a method to quantify the major circulatory form of vitamin D, 25-hydroxyvitamin D, in archived dried blood spots. Over the last 6 years, we have made substantial alterations to the published method to enhance throughput, sensitivity, and assay robustness. RESULTS: With the alterations, the assay was 3 times faster than the previously published assay and had a >10-fold increase in signal strength. Intraassay imprecision decreased from 13.4% to 6.9%, and there was a 5-fold reduction in interfering phospholipids. In actual use over 2 years, the assay showed an interassay imprecision of 11.6%. CONCLUSIONS: This assay has performed reliably over the past 6 years. The practical changes we have made should allow clinical chemists to successfully adapt this method. PMID- 26888894 TI - Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease. AB - BACKGROUND: Increased concentrations of remnant cholesterol are causally associated with increased risk of ischemic heart disease. We tested the hypothesis that increased remnant cholesterol is a risk factor for all-cause mortality in patients with ischemic heart disease. METHODS: We included 5414 Danish patients diagnosed with ischemic heart disease. Patients on statins were not excluded. Calculated remnant cholesterol was nonfasting total cholesterol minus LDL and HDL cholesterol. During 35836 person-years of follow-up, 1319 patients died. RESULTS: We examined both calculated and directly measured remnant cholesterol; importantly, however, measured remnant cholesterol made up only 9% of calculated remnant cholesterol at nonfasting triglyceride concentrations <1 mmol/L (89 mg/dL) and only 43% at triglycerides >5 mmol/L (443 mg/dL). Multivariable-adjusted hazard ratios for all-cause mortality compared with patients with calculated remnant cholesterol concentrations in the 0 to 60th percentiles were 1.2 (95% CI, 1.1-1.4) for patients in the 61st to 80th percentiles, 1.3 (1.1-1.5) for the 81st to 90th percentiles, 1.5 (1.1-1.8) for the 91st to 95th percentiles, and 1.6 (1.2-2.0) for patients in the 96th to 100th percentiles (trend, P < 0.001). Corresponding values for measured remnant cholesterol were 1.0 (0.8-1.1), 1.2 (1.0-1.4), 1.1 (0.9-1.5), and 1.3 (1.1-1.7) (trend, P = 0.006), and for measured LDL cholesterol 1.0 (0.9-1.1), 1.0 (0.8 1.2), 1.0 (0.8-1.3), and 1.1 (0.8-1.4) (trend, P = 0.88). Cumulative survival was reduced in patients with calculated remnant cholesterol >=1 mmol/L (39 mg/dL) vs <1 mmol/L [log-rank, P = 9 * 10(-6); hazard ratio 1.3 (1.2-1.5)], but not in patients with measured LDL cholesterol >=3 mmol/L (116 mg/dL) vs <3 mmol/L [P = 0.76; hazard ratio 1.0 (0.9-1.1)]. CONCLUSIONS: Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease. PMID- 26888895 TI - Plasma Levels of Inflammatory Biomarkers in Peripheral Arterial Disease: Results of a Cohort Study. AB - Previous research analyzed the level of plasma inflammatory markers in patients with coronary disease, but very few studies have evaluated these markers in patients with peripheral arterial disease (PAD). The objective of this study was to investigate the plasma levels of inflammatory markers in patients with PAD and in healthy controls. The following plasma levels of biomarkers were measured in 80 patients with PAD (mean age 68 +/- 5 years) and in 72 healthy participants (mean age 67 +/- 6 years): interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha), L-selectin (LS), neopterin (N), P-selectin (PS), E-selectin (ES), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and matrix metalloproteinase 2 (MMP-2), and 9 (MMP-9). Significantly higher levels of IL-6 (P < .001), TNF-alpha (P < .0001), ES (P < .0001), LS (P < .0001), PS (P < .0001), ICAM-1 (P < .001), VCAM-1 (P < .001), N (P < .001), MMP-2 (P < .001), and MMP-9 (P < .005) were found in the patients with PAD. Patients with PAD show a inflammation marker profile different from that of control participants. Reducing the high plasma levels of inflammatory markers could be a new therapeutic approach both for the prevention and the treatment of PAD. PMID- 26888896 TI - State-of-the-Art Microbiologic Testing for Community-Acquired Meningitis and Encephalitis. AB - Meningitis and encephalitis are potentially life-threatening diseases with a wide array of infectious, postinfectious, and noninfectious causes. Diagnostic testing is central to determining the underlying etiology, treatment, and prognosis, but many patients remain undiagnosed due to suboptimal testing and lack of tests for all pathogens. In this article, we summarize the epidemiology, barriers to diagnosis, and current best tests for meningitis and encephalitis in developed countries. We end with a brief discussion of new test methods, such as multiplex panel-based tests and metagenomic sequencing, which are likely to alter diagnostic strategies for these conditions in the near future. PMID- 26888897 TI - Zika Virus: Diagnostics for an Emerging Pandemic Threat. AB - Zika virus (ZIKV) is anAedesmosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection. PMID- 26888898 TI - Detection and Whole-Genome Sequencing of Carbapenemase-Producing Aeromonas hydrophila Isolates from Routine Perirectal Surveillance Culture. AB - Perirectal surveillance cultures and a stool culture grew Aeromonas species from three patients over a 6-week period and were without epidemiological links. Detection of the blaKPC-2 gene in one isolate prompted inclusion of non Enterobacteriaceae in our surveillance culture workup. Whole-genome sequencing confirmed that the isolates were unrelated and provided data for Aeromonas reference genomes. PMID- 26888899 TI - Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking Induced Conversion. AB - Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni;n= 323), and nasal brush samples were collected from a subpopulation of these animals (n= 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both thePRNPgenotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large scale and rapid automated testing of antemortem samples for CWD. PMID- 26888900 TI - Multicenter Assessment of Gram Stain Error Rates. AB - Gram stains remain the cornerstone of diagnostic testing in the microbiology laboratory for the guidance of empirical treatment prior to availability of culture results. Incorrectly interpreted Gram stains may adversely impact patient care, and yet there are no comprehensive studies that have evaluated the reliability of the technique and there are no established standards for performance. In this study, clinical microbiology laboratories at four major tertiary medical care centers evaluated Gram stain error rates across all nonblood specimen types by using standardized criteria. The study focused on several factors that primarily contribute to errors in the process, including poor specimen quality, smear preparation, and interpretation of the smears. The number of specimens during the evaluation period ranged from 976 to 1,864 specimens per site, and there were a total of 6,115 specimens. Gram stain results were discrepant from culture for 5% of all specimens. Fifty-eight percent of discrepant results were specimens with no organisms reported on Gram stain but significant growth on culture, while 42% of discrepant results had reported organisms on Gram stain that were not recovered in culture. Upon review of available slides, 24% (63/263) of discrepant results were due to reader error, which varied significantly based on site (9% to 45%). The Gram stain error rate also varied between sites, ranging from 0.4% to 2.7%. The data demonstrate a significant variability between laboratories in Gram stain performance and affirm the need for ongoing quality assessment by laboratories. Standardized monitoring of Gram stains is an essential quality control tool for laboratories and is necessary for the establishment of a quality benchmark across laboratories. PMID- 26888901 TI - Detection of Human Herpesvirus 6B (HHV-6B) Reactivation in Hematopoietic Cell Transplant Recipients with Inherited Chromosomally Integrated HHV-6A by Droplet Digital PCR. AB - The presence of inherited chromosomally integrated human herpesvirus 6 (ciHHV-6) in hematopoietic cell transplant (HCT) donors or recipients confounds molecular testing for HHV-6 reactivation, which occurs in 30 to 50% of transplants. Here we describe a multiplex droplet digital PCR clinical diagnostic assay that concurrently distinguishes between HHV-6 species (A or B) and identifies inherited ciHHV-6. By applying this assay to recipient post-HCT plasma and serum samples, we demonstrated reactivation of HHV-6B in 25% (4/16 recipients) of HCT recipients with donor- or recipient-derived inherited ciHHV-6A, underscoring the need for diagnostic testing for HHV-6 infection even in the presence of ciHHV-6. PMID- 26888903 TI - Biographical Feature: Alexander C. Sonnenwirth, Ph.D. PMID- 26888902 TI - Newcastle Disease Viruses Causing Recent Outbreaks Worldwide Show Unexpectedly High Genetic Similarity to Historical Virulent Isolates from the 1940s. AB - Virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), a devastating disease of poultry and wild birds. Phylogenetic analyses clearly distinguish historical isolates (obtained prior to 1960) from currently circulating viruses of class II genotypes V, VI, VII, and XII through XVIII. Here, partial and complete genomic sequences of recent virulent isolates of genotypes II and IX from China, Egypt, and India were found to be nearly identical to those of historical viruses isolated in the 1940s. Phylogenetic analysis, nucleotide distances, and rates of change demonstrate that these recent isolates have not evolved significantly from the most closely related ancestors from the 1940s. The low rates of change for these virulent viruses (7.05 * 10(-5) and 2.05 * 10(-5) per year, respectively) and the minimal genetic distances existing between these and historical viruses (0.3 to 1.2%) of the same genotypes indicate an unnatural origin. As with any other RNA virus, Newcastle disease virus is expected to evolve naturally; thus, these findings suggest that some recent field isolates should be excluded from evolutionary studies. Furthermore, phylogenetic analyses show that these recent virulent isolates are more closely related to virulent strains isolated during the 1940s, which have been and continue to be used in laboratory and experimental challenge studies. Since the preservation of viable viruses in the environment for over 6 decades is highly unlikely, it is possible that the source of some of the recent virulent viruses isolated from poultry and wild birds might be laboratory viruses. PMID- 26888905 TI - Evaluation of the Check-Points Check MDR CT103 and CT103 XL Microarray Kits by Use of Preparatory Rapid Cell Lysis. AB - Using a rapid bacterial lysis method, the Check MDR CT103 and CT103 XL microarrays demonstrated accuracies of 98.1% and 94.2%, respectively, for detection of known resistance genes in 108 multidrug-resistant Gram-negative bacilli. In 45 isolates, 49 previously unrecognized extended-spectrum beta lactamase or plasmid AmpC targets were detected and confirmed by conventional PCR. PMID- 26888904 TI - Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis. AB - Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion?Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion?Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion?Serion kit (P = 0.04). The Bordier and Bio Rad kits had similar specificity (P = 0.8), both higher than that of the Virion?Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion?Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis. PMID- 26888906 TI - Comparison of the Copan eSwab System with an Agar Swab Transport System for Maintenance of Fastidious Anaerobic Bacterium Viability. AB - We compared the eSwab system to a swab with an anaerobic transport semisolid agar system for their capacities to maintain the viability of 20 species of fastidious anaerobes inoculated on the bench and held at ambient or refrigerator temperature for 24 or 48 h. On average, both systems maintained similar viabilities among analogous groups of organisms at both temperatures, although there were quantitative differences among some species. PMID- 26888909 TI - Atypical epidemiology of CTX-M-15 among Enterobacteriaceae from a high diversity of non-clinical niches in Angola. AB - OBJECTIVES: The objective of this study was to investigate the distribution and molecular epidemiology of ESBLs, acquired AmpCs and carbapenemases in Enterobacteriaceae from non-clinical niches in Angola, an under-researched sub Saharan country. METHODS: Eighty-one samples were recovered from healthy persons (n = 18), healthy animals (n = 33) and their environments (n = 10) or aquatic settings (n = 20) in south Angola (2013). Samples were plated onto CHROMagarTM Orientation with/without antibiotics. Standard methods were used for bacterial identification, characterization of bla genes, antibiotic susceptibility testing and conjugation assays. Clonal analysis (XbaI-PFGE, MLST and Escherichia coli phylogroups), location of bla and plasmid characterization (S1-PFGE, I-CeuI-PFGE, replicon typing and hybridization) were also performed. RESULTS: ESBLs (almost exclusively CTX-M-15, 98%) were detected in 21% (45/216) of the isolates, recovered from diverse non-clinical niches and belonging to different Enterobacteriaceae species (mainly E. coli). Acquired AmpCs or carbapenemases were not found. The pandemic B2-ST131 E. coli clone was not identified, but some widespread clonal complexes (CCs) from A (CC10 and CC168), B1 (CC156) or D (CC38) phylogroups were detected. blaCTX-M-15 was variably identified on typeable (29%; 100-335 kb; IncFII, IncFIIK6, IncHI2 and IncY) or non-typeable (16%; 70-330 kb) plasmids or on the chromosome (14%), while for 41% of the isolates its specific location was not determined. CONCLUSIONS: This study reports, for the first time in Angola, an unexpected high occurrence of CTX-M-15 in diverse non-clinical niches and Enterobacteriaceae species, and uncovers novel plasmid replicons in under-researched geographical regions. The diffusion of blaCTX-M-15 through such a high diversity of genetic backgrounds (clones, typeable/non-typeable plasmids and genetic environments) unveils an extraordinary ability for blaCTX-M-15 acquisition and mobilization favoured by unrecognized ecological factors. PMID- 26888908 TI - Ertapenem versus piperacillin/tazobactam for diabetic foot infections in China: a Phase 3, multicentre, randomized, double-blind, active-controlled, non inferiority trial. AB - OBJECTIVES: Few randomized controlled studies have compared antibiotic regimens against diabetic foot infections (DFIs) in Chinese patients. We evaluated the efficacy and safety of ertapenem versus piperacillin/tazobactam for the treatment of DFIs in Chinese patients. METHODS: Patients with moderate to severe DFIs requiring parenteral antibiotics were randomized in a 1 : 1 ratio to receive ertapenem (1.0 g once daily) or piperacillin/tazobactam (4.5 g every 8 h) by 30 min intravenous (iv) infusions for >=5 days. The primary outcome was favourable clinical response at discontinuation of iv therapy (DCIV). An evaluable-patient population was identified for primary analysis of non-inferiority at -15%. Safety was assessed. ClinicalTrials.gov: NCT01370616. RESULTS: Of 565 patients randomized, 443 patients (ertapenem = 219 and piperacillin/tazobactam = 224) were clinically evaluable for primary analysis. In the clinically evaluable population, the proportions of patients with favourable clinical response at DCIV were 93.6% (205/219) and 97.3% (218/224) in the ertapenem and piperacillin/tazobactam groups, respectively (difference: -3.8%, 95% CI: -8.3%, 0.0%). Ertapenem had a significantly lower favourable clinical response rate (91.5% versus 97.2%, 95% CI for difference: -12.1%, -0.3%) at DCIV in severe DFI patients. In the modified ITT population, 88.8% (237/267) and 90.6% (241/266) of patients in the ertapenem and piperacillin/tazobactam groups, respectively, had favourable clinical responses at DCIV (difference: -1.9%, 95% CI: -7.3%, 3.3%). Microbiological eradications of causative pathogens and adverse events were similar between treatment groups. CONCLUSIONS: Treatment with ertapenem was non inferior to piperacillin/tazobactam in Chinese patients with DFIs. Ertapenem treatment resulted in a markedly lower rate of clinical resolution in severe DFIs. PMID- 26888907 TI - Ensembl regulation resources. AB - New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org. PMID- 26888911 TI - Soluble endothelial protein C receptor (sEPCR) as an inflammatory biomarker in naive HIV-infected patients during ART. AB - BACKGROUND: After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting. OBJECTIVES: The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation. PATIENTS AND METHODS: We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD). RESULTS AND CONCLUSIONS: After 48 weeks of ART, in CHI, the sEPCR decrease was significant (P = 0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (r = +0.463, P = 0.007) and HIV RNA decrease (r = -0.363, P = 0.038). In PHI, sEPCR was stable (P = 0.35); there was a correlation between 48 week DD change and IL-6 change (r = +0.696, P = 0.0009) and also between 48 week DD change and sEPCR change (r = +0.553, P = 0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation. PMID- 26888910 TI - Dolutegravir as maintenance monotherapy: first experiences in HIV-1 patients. AB - BACKGROUND: Dolutegravir is recommended as part of combination ART (cART) for HIV 1-infected patients. Toxicities, drug interactions and costs related to cART still warrant the search for improved treatment options. Dolutegravir's high resistance barrier might make it suitable as antiretroviral maintenance monotherapy. The feasibility of this strategy is currently unknown. METHODS: This is a prospective case series on five consecutive HIV-1-infected patients on cART without previous virological failure who switched to dolutegravir monotherapy. All were HIV-RNA suppressed <50 copies/mL and had contraindications to current and alternative combinations of antiretroviral drugs. HIV-RNA was measured at baseline, week 4, week 8, week 12 and every 6 weeks thereafter. Patients would be switched back to their original cART upon confirmed HIV-RNA >50 copies/mL. RESULTS: The five patients had been HIV-RNA suppressed <50 copies/mL for >=1.5 years prior to the initiation of dolutegravir monotherapy. All were on NNRTI containing regimens at the switch. HIV-RNA remained <50 copies/mL at all timepoints in four patients. One patient, with end-stage renal disease and on calcium supplements, had a pre-cART HIV-RNA of 625 000 copies/mL with a CD4 nadir of 120 cells/mm(3) and had HIV-RNA of 8150 copies/mL at week 30. The dolutegravir Ctrough was 0.18 mg/L. This patient did not have acquired resistance or evidence of adherence problems and HIV-RNA was resuppressed after switching to his former cART. CONCLUSIONS: This case series indicates that dolutegravir monotherapy might be a valuable maintenance option in selected HIV-infected patients who are well suppressed on cART, if confirmed by future randomized clinical trials. PMID- 26888912 TI - A chemical susceptibility profile of the Plasmodium falciparum transmission stages by complementary cell-based gametocyte assays. AB - OBJECTIVES: As most available antimalarial drugs are ineffective against the Plasmodium falciparum transmission stages, new drugs against the parasite's gametocytes are urgently needed to combat malaria globally. The unique biology of gametocytes requires assays that need to be specific, to faithfully monitor anti gametocyte activity, and to be easy to perform, cheap and scalable to high throughput screening (HTS). METHODS: We developed an HTS cell-based assay with P. falciparum gametocytes specifically expressing a potent luciferase. To confirm HTS hit activity for several parasite genotypes, the luciferase assay and the gametocyte lactate dehydrogenase (LDH) assay, usable on any parasite isolate, were compared by screening antimalarial drugs and determining IC50 values of anti gametocyte hits from the 'Malaria Box' against early- and late-stage gametocytes. RESULTS: Comparison of the two assays, conducted on the early and on late gametocyte stages, revealed an excellent correlation (R(2) > 0.9) for the IC50 values obtained by the respective readouts. Differences in susceptibility to drugs and compounds between the two parasite developmental stages were consistently measured in both assays. CONCLUSIONS: This work indicates that the luciferase and gametocyte LDH assays are interchangeable and that their specific advantages can be exploited to design an HTS pipeline leading to new transmission blocking compounds. Results from these assays consistently defined a gametocyte chemical susceptibility profile, relevant to the planning of future drug discovery strategies. PMID- 26888913 TI - Alien species as a driver of recent extinctions. AB - We assessed the prevalence of alien species as a driver of recent extinctions in five major taxa (plants, amphibians, reptiles, birds and mammals), using data from the IUCN Red List. Our results show that alien species are the second most common threat associated with species that have gone completely extinct from these taxa since AD 1500. Aliens are the most common threat associated with extinctions in three of the five taxa analysed, and for vertebrate extinctions overall. PMID- 26888915 TI - Patterns of philopatry and longevity contribute to the evolution of post reproductive lifespan in mammals. AB - While menopause has long been known as a characteristic trait of human reproduction, evidence for post-reproductive lifespan (PRLS) has recently been found in other mammals. Adaptive and non-adaptive hypotheses have been proposed to explain the evolution of PRLS, but formal tests of these are rare. We use a phylogenetic approach to evaluate hypotheses for the evolution of PRLS among mammals. In contrast to theoretical models predicting that PRLS may be promoted by male philopatry (which increases relatedness between a female and her group in old age), we find little evidence that male philopatry led to the evolution of a post-reproductive period. However, the proportion of life spent post-reproductive was related to lifespan and patterns of philopatry, suggesting that the duration of PRLS may be impacted by both non-adaptive and adaptive processes. Finally, the proportion of females experiencing PRLS was higher in species with male philopaty and larger groups, in accordance with adaptive models of PRLS. We suggest that the origin of PRLS primarily follows the non-adaptive 'mismatch' scenario, but that patterns of philopatry may subsequently confer adaptive benefits of late life helping. PMID- 26888914 TI - Adaptation to abiotic conditions drives local adaptation in bacteria and viruses coevolving in heterogeneous environments. AB - Parasite local adaptation, the greater performance of parasites on their local compared with foreign hosts, has important consequences for the maintenance of diversity and epidemiology. While the abiotic environment may significantly affect local adaptation, most studies to date have failed either to incorporate the effects of the abiotic environment, or to separate them from those of the biotic environment. Here, we tease apart biotic and abiotic components of local adaptation using the bacterium Pseudomonas fluorescens and its viral parasite bacteriophage Phi2. We coevolved replicate populations of bacteria and phages at three different temperatures, and determined their performance against coevolutionary partners from the same and different temperatures. Crucially, we measured performance at different assay temperatures, which allowed us to disentangle adaptation to biotic and abiotic habitat components. Our results show that bacteria and phages are more resistant and infectious, respectively, at the temperature at which they previously coevolved, confirming that local adaptation to abiotic conditions can play a crucial role in determining parasite infectivity and host resistance. Our work underlines the need to assess host-parasite interactions across multiple relevant abiotic environments, and suggests that microbial adaption to local temperatures can create ecological barriers to dispersal across temperature gradients. PMID- 26888916 TI - Ontogeny and the fossil record: what, if anything, is an adult dinosaur? AB - Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an 'adult' animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered 'adults' in a modern-day field study are considered 'juveniles' or 'subadults' in palaeontological contexts. PMID- 26888917 TI - Light at night, clocks and health: from humans to wild organisms. AB - The increasing use of electric lights has modified the natural light environment dramatically, posing novel challenges to both humans and wildlife. Indeed, several biomedical studies have linked artificial light at night to the disruption of circadian rhythms, with important consequences for human health, such as the increasing occurrence of metabolic syndromes, cancer and reduced immunity. In wild animals, light pollution is associated with changes in circadian behaviour, reproduction and predator-prey interactions, but we know little about the underlying physiological mechanisms and whether wild species suffer the same health problems as humans. In order to fill this gap, we advocate the need for integrating ecological studies in the field, with chronobiological approaches to identify and characterize pathways that may link temporal disruption caused by light at night and potential health and fitness consequences. PMID- 26888919 TI - Has Contemporary Academia Outgrown the Carl Sagan Effect? PMID- 26888918 TI - Usual alcohol consumption and suicide mortality among the Korean elderly in rural communities: Kangwha Cohort Study. AB - BACKGROUND: The evidence from prospective studies on whether greater usual alcohol consumption is associated with a higher risk of death by suicide in the general population is inconclusive. METHODS: 6163 participants (2635 men; 3528 women) in a 1985 survey among rural residents in Korea aged 55 years and above were followed until 2008. A Cox model was used to calculate HRs of suicide death after adjustment for demographic, socioeconomic and health-related confounders. RESULTS: 37 men and 24 women died by suicide. Elderly persons who consumed alcohol daily, 70 g alcohol (5 drinks) or more per drinking day, or 210 g alcohol (15 drinks) or more per week had higher suicide mortality (p<0.05), compared with non-drinkers. An increase of one drinking day per week (HR=1.17, 95% CI 1.05 to 1.31), 70 g (5 drinks) additional alcohol intake per drinking day (HR=1.38, 95% CI 1.13 to 1.70), and 140 g (10 drinks) additional alcohol intake per week was associated with a 17%, 38% and 12% higher risk of suicide death, respectively. Women had a higher relative risk of suicide death associated with alcohol consumption, compared with men. CONCLUSIONS: A greater frequency and amount of usual alcohol consumption was linearly associated with higher suicide death. Given the same amount of alcohol consumption, women might have a higher relative risk of suicide than men. Our findings support 'the lower the better' for alcohol intake, no protective effect of moderate alcohol consumption, and a sex-specific guideline (lower alcohol threshold for women) as actions to prevent suicide death. PMID- 26888920 TI - A Cellular Mechanism for Main and Accessory Olfactory Integration at the Medial Amygdala. PMID- 26888922 TI - Cue Reliability Represented in the Shape of Tuning Curves in the Owl's Sound Localization System. AB - Optimal use of sensory information requires that the brain estimates the reliability of sensory cues, but the neural correlate of cue reliability relevant for behavior is not well defined. Here, we addressed this issue by examining how the reliability of spatial cue influences neuronal responses and behavior in the owl's auditory system. We show that the firing rate and spatial selectivity changed with cue reliability due to the mechanisms generating the tuning to the sound localization cue. We found that the correlated variability among neurons strongly depended on the shape of the tuning curves. Finally, we demonstrated that the change in the neurons' selectivity was necessary and sufficient for a network of stochastic neurons to predict behavior when sensory cues were corrupted with noise. This study demonstrates that the shape of tuning curves can stand alone as a coding dimension of environmental statistics. SIGNIFICANCE STATEMENT: In natural environments, sensory cues are often corrupted by noise and are therefore unreliable. To make the best decisions, the brain must estimate the degree to which a cue can be trusted. The behaviorally relevant neural correlates of cue reliability are debated. In this study, we used the barn owl's sound localization system to address this question. We demonstrated that the mechanisms that account for spatial selectivity also explained how neural responses changed with degraded signals. This allowed for the neurons' selectivity to capture cue reliability, influencing the population readout commanding the owl's sound orienting behavior. PMID- 26888923 TI - Maturation of NaV and KV Channel Topographies in the Auditory Nerve Spike Initiator before and after Developmental Onset of Hearing Function. AB - Auditory nerve excitation and thus hearing depend on spike-generating ion channels and their placement along the axons of auditory nerve fibers (ANFs). The developmental expression patterns and native axonal locations of voltage-gated ion channels in ANFs are unknown. Therefore, we examined the development of heminodes and nodes of Ranvier in the peripheral axons of type I ANFs in the rat cochlea with immunohistochemistry and confocal microscopy. Nodal structures presumably supporting presensory spiking formed between postnatal days 5 (P5) and P7, including Ankyrin-G, NaV1.6, and Caspr. These immature nodal structures lacked low-voltage-activated KV1.1 which was not enriched at juxtaparanodes until approximately P13, concurrent with the developmental onset of acoustic hearing function. Anatomical alignment of ANF spike-initiating heminodes relative to excitatory input from inner hair cell (IHC) ribbon synapses continued until approximately P30. High-voltage-activated KV3.1b and KV2.2 were expressed in mutually exclusive domains: KV3.1b was strictly localized to nodes and heminodes, whereas KV2.2 expression began at the juxtaparanodes and continued centrally along the first internode. At spike-initiating heminodes in the distal osseous spiral lamina, NaV1.1 partly overlapped NaV1.6 and ankyrin-G. ANFs displayed KV7.2 and KV7.3 at heminodes, nodes, internodes, and the unmyelinated synaptic terminal segments beneath IHCs in the organ of Corti. In response to sound, spikes are initiated at the heminode, which is tightly coupled to the IHC ribbon synapse ~20-40 MUm away. These results show that maturation of nodal alignment and ion channel content may underlie postnatal improvements of ANF excitability and discharge synchrony. SIGNIFICANCE STATEMENT: Acoustic and electrical hearing depends on rapid, reliable, and precise spike generation in auditory nerve fibers. A limitation of current models and therapies is a lack of information on the identities and topographies of underlying ion channels. We report the developmental profile of the auditory nerve spike generator with a focus on NaV1.1, NaV1.6, KV1.1, KV2.2, KV3.1b, KV7.2, and KV7.3 in relation to the scaffold ankyrin-G. Molecular anatomy of the spike generator matures in the weeks after developmental onset of hearing function. Subcellular positioning of voltage gated ion channels will enable multicompartmental modeling of auditory nerve responses elicited by afferent chemical neurotransmission from hair cells and modulated by efferent neurotransmitters or evoked by extracellular field stimulation from a cochlear implant. PMID- 26888921 TI - Tau-Driven Neuronal and Neurotrophic Dysfunction in a Mouse Model of Early Tauopathy. AB - Tauopathies are neurodegenerative diseases characterized by intraneuronal inclusions of hyperphosphorylated tau protein and abnormal expression of brain derived neurotrophic factor (BDNF), a key modulator of neuronal survival and function. The severity of both these pathological hallmarks correlate with the degree of cognitive impairment in patients. However, how tau pathology specifically modifies BDNF signaling and affects neuronal function during early prodromal stages of tauopathy remains unclear. Here, we report that the mild tauopathy developing in retinal ganglion cells (RGCs) of the P301S tau transgenic (P301S) mouse induces functional retinal changes by disrupting BDNF signaling via the TrkB receptor. In adult P301S mice, the physiological visual response of RGCs to pattern light stimuli and retinal acuity decline significantly. As a consequence, the activity-dependent secretion of BDNF in the vitreous is impaired in P301S mice. Further, in P301S retinas, TrkB receptors are selectively upregulated, but uncoupled from downstream extracellular signal-regulated kinase (ERK) 1/2 signaling. We also show that the impairment of TrkB signaling is triggered by tau pathology and mediates the tau-induced dysfunction of visual response. Overall our results identify a neurotrophin-mediated mechanism by which tau induces neuronal dysfunction during prodromal stages of tauopathy and define tau-driven pathophysiological changes of potential value to support early diagnosis and informed therapeutic decisions. SIGNIFICANCE STATEMENT: This work highlights the potential molecular mechanisms by which initial tauopathy induces neuronal dysfunction. Combining clinically used electrophysiological techniques (i.e., electroretinography) and molecular analyses, this work shows that in a relevant model of early tauopathy, the retina of the P301S mutant human tau transgenic mouse, mild tau pathology results in functional changes of neuronal activity, likely due to selective impairment of brain-derived neurotrophic factor signaling via its receptor, TrkB. These findings may have important translational implications for early diagnosis in a subset of Alzheimer's disease patients with early visual symptoms and emphasize the need to clarify the pathophysiological changes associated with distinct tauopathy stages to support informed therapeutic decisions and guide drug discovery. PMID- 26888924 TI - Histone Modification of Nedd4 Ubiquitin Ligase Controls the Loss of AMPA Receptors and Cognitive Impairment Induced by Repeated Stress. AB - Stress and the major stress hormone corticosterone induce profound influences in the brain. Altered histone modification and transcriptional dysfunction have been implicated in stress-related mental disorders. We previously found that repeated stress caused an impairment of prefrontal cortex (PFC)-mediated cognitive functions by increasing the ubiquitination and degradation of AMPA-type glutamate receptors via a mechanism depending on the E3 ubiquitin ligase Nedd4. Here, we demonstrated that in PFC of repeatedly stressed rats, active glucocorticoid receptor had the increased binding to the glucocorticoid response element of histone deacetylase 2 (HDAC2) promoter, resulting in the upregulation of HDAC2. Inhibition or knock-down of HDAC2 blocked the stress-induced impairment of synaptic transmission, AMPAR expression, and recognition memory. Furthermore, we found that, in stressed animals, the HDAC2-dependent downregulation of histone methyltransferase Ehmt2 (G9a) led to the loss of repressive histone methylation at the Nedd4-1 promoter and the transcriptional activation of Nedd4. These results have provided an epigenetic mechanism and a potential treatment strategy for the detrimental effects of chronic stress. SIGNIFICANCE STATEMENT: Prolonged stress exposure can induce altered histone modification and transcriptional dysfunction, which may underlie the profound influence of stress in regulating brain functions. We report an important finding about the epigenetic mechanism controlling the detrimental effects of repeated stress on synaptic transmission and cognitive function. First, it has revealed the stress-induced alteration of key epigenetic regulators HDAC2 and Ehmt2, which determines the synaptic and behavioral effects of repeated stress. Second, it has uncovered the stress induced histone modification of the target gene Nedd4, an E3 ligase that is critically involved in the ubiquitination and degradation of AMPA receptors and cognition. Third, it has provided the epigenetic approach, HDAC2 inhibition or knock-down, to rescue synaptic and cognitive functions in stressed animals. PMID- 26888926 TI - REM Sleep Is Causal to Successful Consolidation of Dangerous and Safety Stimuli and Reduces Return of Fear after Extinction. AB - Sleep has a profound impact on memory consolidation. In this study, human participants underwent Pavlovian conditioning and extinction before we manipulated nocturnal memory consolidation by a split-night protocol with 80 healthy male participants in four groups. Recall after a second (recovery) night of sleep revealed that sleeping the first half of the night, which is dominated by slow-wave sleep, did not improve recall. Conversely, sleeping the second half of the night, which is dominated by rapid eye movement (REM) sleep, led to better discrimination between fear-relevant and neutral stimuli in behavioral and autonomic measures. Meanwhile, staying awake in the second half of the night led to an increase of discrimination between extinguished and neutral stimuli, which was paralleled by an activation of the ventromedial prefrontal cortex and amygdala. We conclude that sleep, especially REM sleep, is causal to successful consolidation of dangerous and safety stimuli and reduces return of fear after extinction. SIGNIFICANCE STATEMENT: We use a split-night protocol to investigate the influence of different sleep phases on successful consolidation of conditioned fear and extinction. Such a protocol uses the fact that in humans the first half of the night is dominated by slow-wave sleep, whereas during the second half, rapid eye movement (REM) sleep is more predominant. Our data show that only REM-rich sleep during the second half of the night promoted good discrimination between fear-relevant and neutral stimuli during recall, while staying awake led to a recovery of discrimination between extinguished and neutral stimuli. This suggests that sleep following extinction contributes independently to successful extinction memory consolidation. PMID- 26888927 TI - Preferential Inhibition of Tonically over Phasically Activated NMDA Receptors by Pregnane Derivatives. AB - Postsynaptic N-methyl-d-aspartate receptors (NMDARs) phasically activated by presynaptically released glutamate are critical for synaptic transmission and plasticity. However, under pathological conditions, excessive activation of NMDARs by tonically increased ambient glutamate contributes to excitotoxicity associated with various acute and chronic neurological disorders. Here, using heterologously expressed GluN1/GluN2A and GluN1/GluN2B receptors and rat autaptic hippocampal microisland cultures, we show that pregnanolone sulfate inhibits NMDAR currents induced by a prolonged glutamate application with a higher potency than the NMDAR component of EPSCs. For synthetic pregnanolone derivatives substituted with a carboxylic acid moiety at the end of an aliphatic chain of varying length and attached to the steroid skeleton at C3, the difference in potency between tonic and phasic inhibition increased with the length of the residue. The steroid with the longest substituent, pregnanolone hemipimelate, had no effect on phasically activated receptors while inhibiting tonically activated receptors. In behavioral tests, pregnanolone hemipimelate showed neuroprotective activity without psychomimetic symptoms. These results provide insight into the influence of steroids on neuronal function and stress their potential use in the development of novel therapeutics with neuroprotective action. SIGNIFICANCE STATEMENT: Synaptic activation of N-methyl-d-aspartate receptors (NMDARs) plays a key role in synaptic plasticity, but excessive tonic NMDAR activation mediates excitotoxicity associated with many neurological disorders. Therefore, there is much interest in pharmacological agents capable of selectively blocking tonically activated NMDARs while leaving synaptically activated NMDARs intact. Here, we show that an endogenous neurosteroid pregnanolone sulfate is more potent at inhibiting tonically than synaptically activated NMDARs. Further, we report that a novel synthetic analog of pregnanolone sulfate, pregnanolone hemipimelate, inhibits tonic NMDAR currents without inhibiting the NMDAR component of the EPSC and shows neuroprotective activity in vivo without inducing psychomimetic side effects. These results suggest steroids may have a clinical advantage over other known classes of NMDAR inhibitors. PMID- 26888925 TI - Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice. AB - Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. SIGNIFICANCE STATEMENT: Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and behavioral symptoms observed in the fragile X mouse. This work provides strong evidence that Homer-mGlu5 binding contributes to symptoms associated with neurodevelopmental disorders. PMID- 26888928 TI - Dopaminergic Contributions to Vocal Learning. AB - Although the brain relies on auditory information to calibrate vocal behavior, the neural substrates of vocal learning remain unclear. Here we demonstrate that lesions of the dopaminergic inputs to a basal ganglia nucleus in a songbird species (Bengalese finches, Lonchura striata var. domestica) greatly reduced the magnitude of vocal learning driven by disruptive auditory feedback in a negative reinforcement task. These lesions produced no measureable effects on the quality of vocal performance or the amount of song produced. Our results suggest that dopaminergic inputs to the basal ganglia selectively mediate reinforcement-driven vocal plasticity. In contrast, dopaminergic lesions produced no measurable effects on the birds' ability to restore song acoustics to baseline following the cessation of reinforcement training, suggesting that different forms of vocal plasticity may use different neural mechanisms. SIGNIFICANCE STATEMENT: During skill learning, the brain relies on sensory feedback to improve motor performance. However, the neural basis of sensorimotor learning is poorly understood. Here, we investigate the role of the neurotransmitter dopamine in regulating vocal learning in the Bengalese finch, a songbird with an extremely precise singing behavior that can nevertheless be reshaped dramatically by auditory feedback. Our findings show that reduction of dopamine inputs to a region of the songbird basal ganglia greatly impairs vocal learning but has no detectable effect on vocal performance. These results suggest a specific role for dopamine in regulating vocal plasticity. PMID- 26888929 TI - Amygdala Modulation of Cerebellar Learning. AB - Previous studies showed that amygdala lesions or inactivation slow the acquisition rate of cerebellum-dependent eyeblink conditioning, a type of associative motor learning. The current study was designed to determine the behavioral nature of amygdala-cerebellum interactions, to identify the neural pathways underlying amygdala-cerebellum interactions, and to examine how the amygdala influences cerebellar learning mechanisms in rats. Pharmacological inactivation of the central amygdala (CeA) severely impaired acquisition and retention of eyeblink conditioning, indicating that the amygdala continues to interact with the cerebellum after conditioning is consolidated (Experiment 1). CeA inactivation also substantially reduced stimulus-evoked and learning-related neuronal activity in the cerebellar anterior interpositus nucleus during acquisition and retention of eyeblink conditioning (Experiment 2). A very small proportion of cerebellar neurons responded to the conditioned stimulus (CS) during CeA inactivation. Finally, retrograde and anterograde tracing experiments identified the basilar pontine nucleus at the confluence of outputs from CeA that may support amygdala modulation of CS input to the cerebellum (Experiment 3). Together, these results highlight a role for the CeA in the gating of CS-related input to the cerebellum during motor learning that is maintained even after the conditioned response is well learned. SIGNIFICANCE STATEMENT: The current study is the first to demonstrate that the amygdala modulates sensory-evoked and learning-related neuronal activity within the cerebellum during acquisition and retention of associative learning. The findings suggest a model of amygdala cerebellum interactions in which the amygdala gates conditioned stimulus inputs to the cerebellum through a direct projection from the medial central nucleus to the basilar pontine nucleus. Amygdala gating of sensory input to the cerebellum may be an attention-like mechanism that facilitates cerebellar learning. In contrast to previous theories of amygdala-cerebellum interactions, the sensory gating hypothesis posits that the gating mechanism continues to be necessary for retrieval of cerebellar memory after learning is well established. PMID- 26888931 TI - Distinct beta Band Oscillatory Networks Subserving Motor and Cognitive Control during Gait Adaptation. AB - Everyday locomotion and obstacle avoidance requires effective gait adaptation in response to sensory cues. Many studies have shown that efficient motor actions are associated with MU rhythm (8-13 Hz) and beta band (13-35 Hz) local field desynchronizations in sensorimotor and parietal cortex, whereas a number of cognitive task studies have reported higher behavioral accuracy to be associated with increases in beta band power in prefrontal and sensory cortex. How these two distinct patterns of beta band oscillations interplay during gait adaptation, however, has not been established. Here we recorded 108 channel EEG activity from 18 participants (10 males, 22-35 years old) attempting to walk on a treadmill in synchrony with a series of pacing cue tones, and quickly adapting their step rate and length to sudden shifts in pacing cue tempo. Independent component analysis parsed each participant's EEG data into maximally independent component (IC) source processes, which were then grouped across participants into distinct spatial/spectral clusters. Following cue tempo shifts, mean beta band power was suppressed for IC sources in central midline and parietal regions, whereas mean beta band power increased in IC sources in or near medial prefrontal and dorsolateral prefrontal cortex. In the right dorsolateral prefrontal cortex IC cluster, the beta band power increase was stronger during (more effortful) step shortening than during step lengthening. These results thus show that two distinct patterns of beta band activity modulation accompany gait adaptations: one likely serving movement initiation and execution; and the other, motor control and inhibition. SIGNIFICANCE STATEMENT: Understanding brain dynamics supporting gait adaptation is crucial for understanding motor deficits in walking, such as those associated with aging, stroke, and Parkinson's. Only a few electromagnetic brain imaging studies have examined neural correlates of human upright walking. Here, application of independent component analysis to EEG data recorded during treadmill walking allowed us to uncover two distinct beta band oscillatory cortical networks that are active during gait adaptation to shifts in the tempo of an auditory pacing cue: (8-13 Hz) MU rhythm and (13-35 Hz) beta band power decreases in central and parietal cortex and (14-20 Hz) beta band power increases in frontal brain areas. These results provide a fuller framework for electrophysiological studies of cortical gait control and its disorders. PMID- 26888930 TI - Phasic Dopamine Transmission Reflects Initiation Vigor and Exerted Effort in an Action- and Region-Specific Manner. AB - Initiating a reward-seeking behavior involves deciding on an action, how fast to initiate the action (initiation vigor), as well as how much effort to exert. These processes are thought to involve the mesolimbic dopamine system. Dopamine levels in the ventral striatum rise before initiating a reliably reinforced behavior. However, it is unknown whether dopamine is similarly involved with unreinforced actions (inactive lever presses, premature food port entries, insufficient number of active lever presses). Furthermore, does the dopamine response when initiating an action reflect specific aspects of motivated behavior, such as initiation vigor and exerted effort? Here, we analyzed voltammetry recordings of dopamine levels in the nucleus accumbens (NAcc) core and shell in rats working for food under a progressive ratio reinforcement schedule. We examined dopamine levels when rats initiated distinct actions (active lever presses, inactive lever presses, food port entries) that were temporally separated from cue- and reward-evoked dopamine release. Active lever pressing bouts were preceded by elevated dopamine release in the NAcc shell, as well as in the NAcc core, although only when rats exhibited high initiation vigor. Dopamine levels were transiently reduced in the NAcc core following an unreinforced food port entry and were unchanged throughout the NAcc when initiating inactive lever presses. The effort exerted and vigor to initiate a bout of active lever presses were signaled by dopamine transmission in the NAcc core, but not in the NAcc shell. These results demonstrate that the dopamine response when initiating a behavior is both region- and action-specific. SIGNIFICANCE STATEMENT: Exogenous activation of the mesolimbic dopamine system facilitates motivated behavior. However, a direct relationship has not been established between endogenous phasic dopamine transmission and measures of motivation, such as the vigor to initiate an action and the effort exerted in a bout of activity. The present work demonstrates that the dopamine response when initiating an action depends both upon where dopamine is released and what action is performed. Furthermore, dopamine reflects measures of motivated behavior selectively within the nucleus accumbens core. PMID- 26888932 TI - Distorted Tonotopic Coding of Temporal Envelope and Fine Structure with Noise Induced Hearing Loss. AB - People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) >1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. SIGNIFICANCE STATEMENT: Speech-perception problems associated with noise overexposure are pervasive in today's society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss. PMID- 26888933 TI - Perceptual Learning at a Conceptual Level. AB - Humans can learn to abstract and conceptualize the shared visual features defining an object category in object learning. Therefore, learning is generalizable to transformations of familiar objects and even to new objects that differ in other physical properties. In contrast, visual perceptual learning (VPL), improvement in discriminating fine differences of a basic visual feature through training, is commonly regarded as specific and low-level learning because the improvement often disappears when the trained stimulus is simply relocated or rotated in the visual field. Such location and orientation specificity is taken as evidence for neural plasticity in primary visual cortex (V1) or improved readout of V1 signals. However, new training methods have shown complete VPL transfer across stimulus locations and orientations, suggesting the involvement of high-level cognitive processes. Here we report that VPL bears similar properties of object learning. Specifically, we found that orientation discrimination learning is completely transferrable between luminance gratings initially encoded in V1 and bilaterally symmetric dot patterns encoded in higher visual cortex. Similarly, motion direction discrimination learning is transferable between first- and second-order motion signals. These results suggest that VPL can take place at a conceptual level and generalize to stimuli with different physical properties. Our findings thus reconcile perceptual and object learning into a unified framework. SIGNIFICANCE STATEMENT: Training in object recognition can produce a learning effect that is applicable to new viewing conditions or even to new objects with different physical properties. However, perceptual learning has long been regarded as a low-level form of learning because of its specificity to the trained stimulus conditions. Here we demonstrate with new training tactics that visual perceptual learning is completely transferrable between distinct physical stimuli. This finding indicates that perceptual learning also operates at a conceptual level in a stimulus-invariant manner. PMID- 26888935 TI - Live Imaging of Kv7.2/7.3 Cell Surface Dynamics at the Axon Initial Segment: High Steady-State Stability and Calpain-Dependent Excitotoxic Downregulation Revealed. AB - The voltage-gated K(+) channels Kv7.2 and Kv7.3 are located at the axon initial segment (AIS) and exert strong control over action potential generation. Therefore, changes in their localization or cell surface numbers are likely to influence neuronal signaling. However, nothing is known about the cell surface dynamics of Kv7.2/7.3 at steady state or during short-term neuronal stimulation. This is primarily attributable to their membrane topology, which hampers extracellular epitope tagging. Here we circumvent this limitation by fusing an extra phluorin-tagged helix to the N terminus of human Kv7.3. This seven transmembrane chimera, named super ecliptic phluorin (SEP)-TAC-7.3, functions and traffics as a wild-type (WT) channel. We expressed SEP-TAC-7.3 in dissociated rat hippocampal neurons to examine the lateral mobility, surface numbers, and localization of AIS Kv7.2/7.3 heteromers using live imaging. We discovered that they are extraordinarily stable and exhibit a very low surface mobility both during steady state and neuronal stimulation. In the latter case, we also found that neither localization nor cell surface numbers were changed. However, at high glutamate loads, we observed a rapid irreversible endocytosis of Kv7.2/7.3, which required the activation of NR2B-containing NMDA receptors, Ca(2+) influx, and calpain activation. This excitotoxic mechanism may be specific to ankyrin G-bound AIS proteins because Nav1.2 channels, but not AIS GABAA receptors, were also endocytosed. In conclusion, we have, for the first time, characterized the cell surface dynamics of a full-length Kv7 channel using a novel chimeric strategy. This approach is likely also applicable to other Kv channels and thus of value for the additional characterization of this ion channel subfamily. SIGNIFICANCE STATEMENT: The voltage-gated K(+) channels Kv7.2 and Kv7.3 exert strong control over action potential generation, but little is known about their cell surface dynamics. Using a novel phluorin-based approach, we here show that these channels are highly stable at steady state and different types of neuronal stimulation. However, at high glutamate loads, they undergo a rapid calpain-dependent endocytosis that likely represents an early response during excitotoxic states. PMID- 26888934 TI - Impaired Dendritic Development and Memory in Sorbs2 Knock-Out Mice. AB - Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults and genetic defects contribute to the etiology of intellectual disability. Copy number variations of SORBS2 have been linked to intellectual disability. However, the neurobiological function of SORBS2 in the brain is unknown. The SORBS2 gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) protein in non-neuronal tissues and is alternatively spliced in the brain to encode nArgBP2 protein. We found nArgBP2 colocalized with F-actin at dendritic spines and growth cones in cultured hippocampal neurons. In the mouse brain, nArgBP2 was highly expressed in the cortex, amygdala, and hippocampus, and enriched in the outer one-third of the molecular layer in dentate gyrus. Genetic deletion of Sorbs2 in mice led to reduced dendritic complexity and decreased frequency of AMPAR-miniature spontaneous EPSCs in dentate gyrus granule cells. Behavioral characterization revealed that Sorbs2 deletion led to a reduced acoustic startle response, and defective long-term object recognition memory and contextual fear memory. Together, our findings demonstrate, for the first time, an important role for nArgBP2 in neuronal dendritic development and excitatory synaptic transmission, which may thus inform exploration of neurobiological basis of SORBS2 deficiency in intellectual disability. SIGNIFICANCE STATEMENT: Copy number variations of the SORBS2 gene are linked to intellectual disability, but the neurobiological mechanisms are unknown. We found that nArgBP2, the only neuronal isoform encoded by SORBS2, colocalizes with F-actin at neuronal dendritic growth cones and spines. nArgBP2 is highly expressed in the cortex, amygdala, and dentate gyrus in the mouse brain. Genetic deletion of Sorbs2 in mice leads to impaired dendritic complexity and reduced excitatory synaptic transmission in dentate gyrus granule cells, accompanied by behavioral deficits in acoustic startle response and long term memory. This is the first study of Sorbs2 function in the brain, and our findings may facilitate the study of neurobiological mechanisms underlying SORBS2 deficiency in the development of intellectual disability. PMID- 26888937 TI - Cell-Type Specific Phase Precession in Layer II of the Medial Entorhinal Cortex. AB - The identity of phase-precessing cells in the entorhinal cortex is unknown. Here, we used a classifier derived from cell-attached recordings to separate putative pyramidal cells and putative stellate cells recorded extracellularly in layer II of the medial entorhinal cortex in rats. Using a novel method to identify single runs as temporal periods of elevated spiking activity, we find that both cell types show phase precession but putative stellate cells show steeper slopes of phase precession and larger phase ranges. As the two classes of cells have different projection patterns, phase precession is differentially passed on to different subregions of the hippocampal formation. SIGNIFICANCE STATEMENT: It is a great challenge for neuroscience to reveal the cellular basis of cognitive functions. One such function is the ability to learn and recollect temporal sequences of events. The representation of sequences in the brain is thought to require temporally structured activity of nerve cells. How different types of neurons generate temporally structured activity is currently unknown. In the present study, we use a computational classification procedure to separate different cell types and find that a subpopulation of cells, so-called stellate neurons, exhibits clear temporal coding. Contrary to the stellate cells, pyramidal cells show weaker temporal coding. This discovery sheds light on the cellular basis of temporal coding in the brain. PMID- 26888936 TI - Guidance of Axons by Local Coupling of Retrograde Flow to Point Contact Adhesions. AB - Growth cones interact with the extracellular matrix (ECM) through integrin receptors at adhesion sites termed point contacts. Point contact adhesions link ECM proteins to the actin cytoskeleton through numerous adaptor and signaling proteins. One presumed function of growth cone point contacts is to restrain or "clutch" myosin-II-based filamentous actin (F-actin) retrograde flow (RF) to promote leading edge membrane protrusion. In motile non-neuronal cells, myosin-II binds and exerts force upon actin filaments at the leading edge, where clutching forces occur. However, in growth cones, it is unclear whether similar F-actin clutching forces affect axon outgrowth and guidance. Here, we show in Xenopus spinal neurons that RF is reduced in rapidly migrating growth cones on laminin (LN) compared with non-integrin-binding poly-d-lysine (PDL). Moreover, acute stimulation with LN accelerates axon outgrowth over a time course that correlates with point contact formation and reduced RF. These results suggest that RF is restricted by the assembly of point contacts, which we show occurs locally by two channel imaging of RF and paxillin. Further, using micropatterns of PDL and LN, we demonstrate that individual growth cones have differential RF rates while interacting with two distinct substrata. Opposing effects on RF rates were also observed in growth cones treated with chemoattractive and chemorepulsive axon guidance cues that influence point contact adhesions. Finally, we show that RF is significantly attenuated in vivo, suggesting that it is restrained by molecular clutching forces within the spinal cord. Together, our results suggest that local clutching of RF can control axon guidance on ECM proteins downstream of axon guidance cues. SIGNIFICANCE STATEMENT: Here, we correlate point contact adhesions directly with clutching of filamentous actin retrograde flow (RF), which our findings strongly suggest guides developing axons. Acute assembly of new point contact adhesions is temporally and spatially linked to attenuation of RF at sites of forward membrane protrusion. Importantly, clutching of RF is modulated by extracellular matrix (ECM) proteins and soluble axon guidance cues, suggesting that it may regulate axon guidance in vivo. Consistent with this notion, we found that RF rates of spinal neuron growth cones were slower in vivo than what was observed in vitro. Together, our study provides the best evidence that growth cone-ECM adhesions clutch RF locally to guide axons in vivo. PMID- 26888938 TI - Functional Architecture of the Rat Parasubiculum. AB - The parasubiculum is a major input structure of layer 2 of medial entorhinal cortex, where most grid cells are found. Here we investigated parasubicular circuits of the rat by anatomical analysis combined with juxtacellular recording/labeling and tetrode recordings during spatial exploration. In tangential sections, the parasubiculum appears as a linear structure flanking the medial entorhinal cortex mediodorsally. With a length of ~5.2 mm and a width of only ~0.3 mm (approximately one dendritic tree diameter), the parasubiculum is both one of the longest and narrowest cortical structures. Parasubicular neurons span the height of cortical layers 2 and 3, and we observed no obvious association of deep layers to this structure. The "superficial parasubiculum" (layers 2 and 1) divides into ~15 patches, whereas deeper parasubicular sections (layer 3) form a continuous band of neurons. Anterograde tracing experiments show that parasubicular neurons extend long "circumcurrent" axons establishing a "global" internal connectivity. The parasubiculum is a prime target of GABAergic and cholinergic medial septal inputs. Other input structures include the subiculum, presubiculum, and anterior thalamus. Functional analysis of identified and unidentified parasubicular neurons shows strong theta rhythmicity of spiking, a large fraction of head-direction selectivity (50%, 34 of 68), and spatial responses (grid, border and irregular spatial cells, 57%, 39 of 68). Parasubicular output preferentially targets patches of calbindin-positive pyramidal neurons in layer 2 of medial entorhinal cortex, which might be relevant for grid cell function. These findings suggest the parasubiculum might shape entorhinal theta rhythmicity and the (dorsoventral) integration of information across grid scales. SIGNIFICANCE STATEMENT: Grid cells in medial entorhinal cortex (MEC) are crucial components of an internal navigation system of the mammalian brain. The parasubiculum is a major input structure of layer 2 of MEC, where most grid cells are found. Here we provide a functional and anatomical characterization of the parasubiculum and show that parasubicular neurons display unique features (i.e., strong theta rhythmicity of firing, prominent head direction selectivity, and output selectively targeted to layer 2 pyramidal cell patches of MEC). These features could contribute to shaping the temporal and spatial code of downstream grid cells in entorhinal cortex. PMID- 26888939 TI - Neural Correlates of Vocal Production and Motor Control in Human Heschl's Gyrus. AB - The present study investigated how pitch frequency, a perceptually relevant aspect of periodicity in natural human vocalizations, is encoded in Heschl's gyrus (HG), and how this information may be used to influence vocal pitch motor control. We recorded local field potentials from multicontact depth electrodes implanted in HG of 14 neurosurgical epilepsy patients as they vocalized vowel sounds and received brief (200 ms) pitch perturbations at 100 Cents in their auditory feedback. Event-related band power responses to vocalizations showed sustained frequency following responses that tracked voice fundamental frequency (F0) and were significantly enhanced in posteromedial HG during speaking compared with when subjects listened to the playback of their own voice. In addition to frequency following responses, a transient response component within the high gamma frequency band (75-150 Hz) was identified. When this response followed the onset of vocalization, the magnitude of the response was the same for the speaking and playback conditions. In contrast, when this response followed a pitch shift, its magnitude was significantly enhanced during speaking compared with playback. We also observed that, in anterolateral HG, the power of high gamma responses to pitch shifts correlated with the magnitude of compensatory vocal responses. These findings demonstrate a functional parcellation of HG with neural activity that encodes pitch in natural human voice, distinguishes between self-generated and passively heard vocalizations, detects discrepancies between the intended and heard vocalization, and contains information about the resulting behavioral vocal compensations in response to auditory feedback pitch perturbations. SIGNIFICANCE STATEMENT: The present study is a significant contribution to our understanding of sensor-motor mechanisms of vocal production and motor control. The findings demonstrate distinct functional parcellation of core and noncore areas within human auditory cortex on Heschl's gyrus that process natural human vocalizations and pitch perturbations in the auditory feedback. In addition, our data provide evidence for distinct roles of high gamma neural oscillations and frequency following responses for processing periodicity in human vocalizations during vocal production and motor control. PMID- 26888940 TI - Enhancing GABA Signaling during Middle Adulthood Prevents Age-Dependent GABAergic Interneuron Decline and Learning and Memory Deficits in ApoE4 Mice. AB - Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease (AD). However, the underlying mechanisms are still poorly understood. We previously reported that female apoE4 knock-in (KI) mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined by Morris water maze (MWM), in aged mice. Enhancing GABA signaling by treating aged apoE4-KI mice with the GABAA receptor potentiator pentobarbital (PB) for 4 weeks before and during MWM rescued the learning and memory deficits. Here, we report that withdrawal of PB treatment for 2 weeks before MWM abolished the rescue in aged apoE4-KI mice, suggesting the importance of continuously enhancing GABA signaling in the rescue. However, treating apoE4-KI mice during middle adulthood (9-11 months of age) with PB for 6 weeks prevented age-dependent hilar GABAergic interneuron decline and learning and memory deficits, when examined at 16 month of age. These data imply that increasing inhibitory tone after substantial GABAergic interneuron loss may be an effective symptomatic, but not a disease-modifying, treatment for AD related to apoE4, whereas a similar intervention before substantial interneuron loss could be a disease-modifying therapeutic. SIGNIFICANCE STATEMENT: We previously reported that female apoE4-KI mice had an age-dependent decline in hilar GABAergic interneurons that correlated with the extent of cognitive deficits in aged mice. The current study demonstrates that enhancing GABA signaling by treating aged apoE4-KI mice with a GABAA receptor potentiator pentobarbital (PB) before and during behavioral tests rescued the cognitive deficits; but withdrawal of PB treatment for 2 weeks before the tests abolished the rescue, suggesting the importance of continuously enhancing GABA signaling. However, treating apoE4-KI mice during middle adulthood with PB for a short period of time prevented age dependent hilar GABAergic interneuron decline and cognitive deficits late in life, suggesting early intervention by enhancing GABA signaling as a potential strategy to prevent AD related to apoE4. PMID- 26888942 TI - "One and the Same the World Over": The International Culture of Surgical Exchange in an Age of Globalization, 1870-1914. AB - This paper examines the international exchange in surgery in the decades before World War I, a period of growing globalization in communication and transport. Focusing on Europe and North America, it looks first at the various means of exchange, especially surgical travel and the culture emerging around it and follows specific directions of exchange, from France and Britain, first to the German-speaking countries and finally to North America. Subsequently, the account turns to international organizations as an important means of exchange in this time period. The International Society of Surgery, in particular, provided a forum for a vivid internationalist discourse, which, however, stood in tension with simultaneous nationalist tendencies leading up to World War I. The paper finally discusses how the international exchange and communication at the time can be seen as an instance of modern surgeons claiming-and simultaneously trying to create-the global universality of surgical knowledge and practices, making sure that surgery is the same the world over. PMID- 26888941 TI - The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy. AB - Chronic treatment of methicillin-resistant Staphylococcus aureus strains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC50= 295 +/- 1.0MUM) and time-dependent (KI= 216 +/- 41MUM and kinact= 0.0179 +/- 0.001 min(-1)) inhibitor of CYP3A4-catalyzed midazolam-1' hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC50 value of 157 +/- 1.0MUM and was devoid of breast cancer resistance protein inhibition (IC50> 500MUM). In contrast, FA showed potent inhibition of OATP1B1- and OATP1B3 specific rosuvastatin transport with IC50 values of 1.59MUM and 2.47MUM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC50= 2.26MUM) and Oatp1b2 (IC50= 4.38MUM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity. PMID- 26888943 TI - My First Hundred Manuscripts / Mes 100 premiers manuscrits. PMID- 26888944 TI - Manuscript Submission Guidelines: Journal of Cutaneous Medicine and Surgery. PMID- 26888945 TI - Borderline Lepromatous Leprosy: A Case to Remember. PMID- 26888946 TI - Patients' access to biological therapy in chronic inflammatory conditions; per capita GDP does not explain the intercountry differences. PMID- 26888947 TI - Response to: 'Reporting of potential immunogenicity with biologic drugs: clarity and accuracy required' by Moots et al. PMID- 26888948 TI - The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. AB - A European League Against Rheumatism (EULAR) task force was established to define points to consider on use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Based on a systematic literature review and pregnancy exposure data from several registries, statements on the compatibility of antirheumatic drugs during pregnancy and lactation were developed. The level of agreement among experts in regard to statements and propositions of use in clinical practice was established by Delphi voting. The task force defined 4 overarching principles and 11 points to consider for use of antirheumatic drugs during pregnancy and lactation. Compatibility with pregnancy and lactation was found for antimalarials, sulfasalazine, azathioprine, ciclosporin, tacrolimus, colchicine, intravenous immunoglobulin and glucocorticoids. Methotrexate, mycophenolate mofetil and cyclophosphamide require discontinuation before conception due to proven teratogenicity. Insufficient documentation in regard to fetal safety implies the discontinuation of leflunomide, tofacitinib as well as abatacept, rituximab, belimumab, tocilizumab, ustekinumab and anakinra before a planned pregnancy. Among biologics tumour necrosis factor inhibitors are best studied and appear reasonably safe with first and second trimester use. Restrictions in use apply for the few proven teratogenic drugs and the large proportion of medications for which insufficient safety data for the fetus/child are available. Effective drug treatment of active inflammatory rheumatic disease is possible with reasonable safety for the fetus/child during pregnancy and lactation. The dissemination of the data to health professionals and patients as well as their implementation into clinical practice may help to improve the management of pregnant and lactating patients with rheumatic disease. PMID- 26888949 TI - Surface strain measurements of fingertip skin under shearing. AB - The temporal evolution of surface strain, resulting from a combination of normal and tangential loading forces on the fingerpad, was calculated from high resolution images. A customized robotic device loaded the fingertip with varying normal force, tangential direction and tangential speed. We observed strain waves that propagated from the periphery to the centre of the contact area. Consequently, different regions of the contact area were subject to varying degrees of compression, stretch and shear. The spatial distribution of both the strains and the strain energy densities depended on the stimulus direction. Additionally, the strains varied with the normal force level and were substantial, e.g. peak strains of 50% with a normal force of 5 N, i.e. at force levels well within the range of common dexterous manipulation tasks. While these observations were consistent with some theoretical predictions from contact mechanics, we also observed substantial deviations as expected given the complex geometry and mechanics of fingertips. Specifically, from in-depth analyses, we conclude that some of these deviations depend on local fingerprint patterns. Our data provide useful information for models of tactile afferent responses and background for the design of novel haptic interfaces. PMID- 26888950 TI - Finite-element model of the active organ of Corti. AB - The cochlear amplifier that provides our hearing with its extraordinary sensitivity and selectivity is thought to be the result of an active biomechanical process within the sensory auditory organ, the organ of Corti. Although imaging techniques are developing rapidly, it is not currently possible, in a fully active cochlea, to obtain detailed measurements of the motion of individual elements within a cross section of the organ of Corti. This motion is predicted using a two-dimensional finite-element model. The various solid components are modelled using elastic elements, the outer hair cells (OHCs) as piezoelectric elements and the perilymph and endolymph as viscous and nearly incompressible fluid elements. The model is validated by comparison with existing measurements of the motions within the passive organ of Corti, calculated when it is driven either acoustically, by the fluid pressure or electrically, by excitation of the OHCs. The transverse basilar membrane (BM) motion and the shearing motion between the tectorial membrane and the reticular lamina are calculated for these two excitation modes. The fully active response of the BM to acoustic excitation is predicted using a linear superposition of the calculated responses and an assumed frequency response for the OHC feedback. PMID- 26888951 TI - Host trait combinations drive abundance and canopy distribution of atmospheric bromeliad assemblages. AB - Epiphytes are strongly dependent on the conditions created by their host's traits and a certain degree of specificity is expected between them, even if these species are largely abundant in a series of tree hosts of a given environment, as in the case of atmospheric bromeliads. Despite their considerable abundance in these environments, we hypothesize that stochasticity alone cannot explain the presence and abundance of atmospheric bromeliads on host trees, since host traits could have a greater influence on the establishment of these bromeliads. We used secondary and reforested seasonal forests and three distinct silvicultures to test whether species richness, phylogenetic diversity and functional diversity of trees can predict the differential presence, abundance and distribution of atmospheric bromeliads on hosts. We compared the observed parameters of their assemblage with null models and performed successive variance hierarchic partitions of abundance and distribution of the assemblage to detect the influence of multiple traits of the tree hosts. Our results do not indicate direct relationships between the abundance of atmospheric bromeliads and phylogenetic or functional diversity of trees, but instead indicate that bromeliads occurred on fewer tree species than expected by chance. We distinguished functional tree patterns that can improve or reduce the abundance of atmospheric bromeliads, and change their distribution on branches and trunk. While individual tree traits are related to increased abundance, species traits are related to the canopy distribution of atmospheric bromeliad assemblages. A balance among these tree functional patterns drives the atmospheric bromeliad assemblage of the forest patches. PMID- 26888952 TI - Time to redefine success? TICI 3 versus TICI 2b recanalization in middle cerebral artery occlusion treated with thrombectomy. AB - BACKGROUND: The Thrombolysis in Cerebral Infarction (TICI) scale is the most widely applied scoring system to grade technical results of recanalizing therapies in acute ischemic stroke (AIS). TICI 2b and TICI 3 are conventionally subsumed as 'successful recanalization'. Previous studies reported conflicting results for the clinical relevance of achieving complete (TICI 3) versus 'almost' complete reperfusion (TICI 2b). OBJECTIVE: To examine if neurologic outcome differs significantly between TICI 2b and TICI 3 in patients with AIS with middle cerebral artery (MCA) occlusion treated 'successfully' with mechanical thrombectomy (MTE). METHODS: Retrospective analysis of prospectively collected data from 352 consecutive patients with isolated MCA occlusion subjected to MTE between January 2007 and July 2015. RESULTS: 262 of the 277 successfully treated patients had adequate follow-up and were included. Patients (n=119) in the TICI 3 group had a lower National Institutes of Health Stroke Scale score at discharge (NIHSS-DIS; median 5 vs 7, p=0.005), and showed higher rates of strong neurologic improvement (DeltaNIHSS>=8 or NIHSS-DIS<=1, 68.4% vs 37.1%, p=0.002) and favorable NIHSS outcome (NIHSS-DIS<=5, 49.2% vs 31.9%, p=0.005). Hospital stays were shorter in the TICI 3 group (median 10 vs 12 days, p=0.014). After adjusting for relevant baseline and treatment parameters, TICI 3 was independently associated with strong neurologic improvement (OR=4.3, 95% CI 2.2 to 8.3, p<0.001) and favorable NIHSS outcome (OR=3.0, 95% CI 1.5 to 6.3, p=0.003). CONCLUSIONS: Neurologic outcome is substantially better in TICI 3 than TICI 2b patients, and hospital stays are shorter. Endovascular strategies that consequently strive to achieve TICI 3 may be warranted and cost-effective, and should be examined by future research. TICI 3 rates should be included as a safety measure in studies evaluating MTE devices and techniques. PMID- 26888953 TI - ASPECTS discrepancies between CT and MR imaging: analysis and implications for triage protocols in acute ischemic stroke. AB - BACKGROUND: Optimal imaging triage for intervention for large vessel occlusions remains unclear. MR-based imaging provides ischemic core volumes at the cost of increased imaging time. CT Alberta Stroke Program Early CT Score (ASPECTS) estimates are faster, but may be less sensitive. OBJECTIVE: To assesses the rate at which MRI changed management in comparison with CT imaging alone. METHODS: Retrospective analysis of patients with acute ischemic stroke undergoing imaging triage for endovascular therapy was performed between 2008 and 2013. Univariate and multivariate analyses were performed. Multivariate logistic regression was used to evaluate the effect of time on disagreement in MRI and CT ASPECTS scores. RESULTS: A total of 241 patients underwent both diffusion-weighted imaging (DWI) and CT. Six patients with DWI ASPECTS >=6 and CT ASPECTS <6 were omitted, leaving 235 patients. For 47 patients, disagreement between the two modalities resulted in different treatment recommendations. The estimated probability of disagreement was 20.0% (95% CI 15.4% to 25.6%). In a multivariate logistic regression, CT ASPECTS >7 (p=0.004) and admission National Institutes of Health Stroke Scale (NIHSS) score <16 (p=0.008) were simultaneously significant predictors of agreement in ASPECTS. The time between modalities was a marginally significant predictor (p=0.080). CONCLUSIONS: The study suggests that patients with NIHSS scores at admission of <16 and patients with CT ASPECTS >7 have a higher likelihood of agreement between CT and DWI based on an ASPECTS cut-off value of 6. Additional MRI for triage in patients with NIHSS at admission of >16, and ASPECTS of 6 or 7 may be more likely to change management. Unsurprisingly, patients with low CT ASPECTS had good correlation with MRI ASPECTS. PMID- 26888954 TI - Training Guidelines for Endovascular Ischemic Stroke Intervention: An International multi-society consensus document. PMID- 26888955 TI - Classical Hodgkin Lymphoma Arising Adjacent to a Breast Implant. AB - Breast implant-associated lymphoma has recently gained wide recognition. Anaplastic large cell lymphoma (ALCL) is the most frequently diagnosed subtype in this setting but the spectrum is broadening. A 66-year-old woman developed swelling and itch around her saline implant 6 years after its insertion. Imaging revealed a fluid collection surrounding the implant with an adjacent mass. Microscopy showed sclerotic tissue punctuated by discrete cellular nodules comprising small lymphocytes, eosinophils and interspersed large atypical Hodgkin Reed-Sternberg (HRS)-like cells. The HRS-like cells stained positively for CD30 and CD15 by immunohistochemistry. Small T-lymphocytes formed rosettes around HRS like cells. Appearances were consistent with classical Hodgkin lymphoma (HL). Multiplex polymerase chain reaction demonstrated no clonal rearrangements of immunoglobulin or T-cell receptor genes, however, a t(14;18)(q32;q21)BCL2-JH translocation involving the major breakpoint region of the bcl2 gene was present. Staging positron emission tomography-computed tomography scan revealed FDG-avid masses in the right axilla and pelvis. Subsequent pathological examination identified low-grade follicular lymphoma (FL) with a t(14;18) translocation at these sites. To our knowledge, this is the first case of HL arising adjacent to a breast implant. An awareness of this diagnosis is important as classical HL, with its prominent mixed inflammatory background, may be overlooked as a reactive process when histologically assessing capsulectomy specimens. It is also important in the differential diagnosis for implant-associated ALCL as both contain large atypical CD30-positive cells highlighting the need for full immunohistochemical and molecular workup in such cases. This case also adds to the large body of literature regarding the association between HL and FL. PMID- 26888956 TI - Assessment of CD-105 as an Angiogenic Modulator in Odontogenic Myxomas and Dental Follicles. AB - Aim Odontogenic myxoma is a benign intraosseous neoplasm of the jaws, with a locally aggressive behavior and a high recurrence rate. CD-105 is a homodimeric cell membrane glycoprotein and is a component of the TGF-beta1 growth factor receptor complex that modulates angiogenesis by regulating the proliferation, differentiation and cellular migration. The aim of this study is to quantify the microvascular density of the odontogenic myxoma based on the expression of CD 105. Materials and Methods The analysis included 18 odontogenic myxoma and 18 dental follicles as controls. A standard immunohistochemical procedure was performed with the CD-105 antibody. Five representative fields (40*) of the odontogenic myxoma and the dental follicles were selected to determine the microvascular density, which was then followed by a descriptive and comparative statistical analysis. Results Dental follicles presented a significantly higher microvascular density compared with odontogenic myxoma (P = .001). The odontogenic myxoma smaller than 3 cm showed a greater microvascular density than those larger than 3 cm in size (P > .05), and the microvascular density was lower in large odontogenic myxomas as compared with the dental follicles (P = .003). Conclusion A weaker expression of CD-105 in odontogenic myxoma might indicate a lower angiogenic activity, suggesting that vascular proliferation has a limited role in the growth mechanisms and in the aggressive behavior of this neoplasm. PMID- 26888957 TI - Bizarre Stromal Cells in an Endometrial Polyp. AB - Bizarre stromal cells have been reported in vulvovaginal polyps, as well as in nongynecologic sites, with caution not to mistake them for malignancy. Similar atypical stromal cells have only rarely been reported in the endometrium. We present a case found incidentally in a postmenopausal woman, and review the literature. PMID- 26888958 TI - Malignant Peripheral Nerve Sheath Tumor With Osseous Heterologous Differentiation in Uncommon Locations (Heart and Retropharynx). AB - We report two cases of malignant peripheral nerve sheath tumor (MPNST) in an uncommon location (heart and retropharynx) both with divergent osseous heterologous differentiation. We present the pathological and immunohistochemical studies that confirmed the neurogenic origin. The histopathology of the tumor arising in the retropharynx showed a transition from a neurofibroma to MPNST, making this a new report of an MPNST arising from a plexiform neurofibroma without neurofibromatosis. Primary cardiac MPNST with osseous differentiation has never been reported before. In conclusion, the histology of MPNSTs is very heterogeneous, showing no specific diagnostic immunoprofile or genetic alteration. Thus, it is important to rule out other histologically similar tumors, particularly in cases arising in uncommon locations or tumors with divergent heterologous differentiation. PMID- 26888959 TI - Post-traumatic amnesia and confusional state: hazards of retrospective assessment. AB - Retrospective assessment of post-traumatic amnesia (PTA) must take into account factors other than traumatic brain injury (TBI) which may impact on memory both at the time of injury and subsequent to the injury. These include analgesics, anaesthesia required for surgery, and the development of acute or post-traumatic stress disorder. This is relevant in clinical and medicolegal settings. Repeated assessments of the post-injury state, involving tests for continuing amnesia, risk promoting recall of events suggested by the examiner, or generating confabulations. The PTA syndrome affects the categorical autobiographical memory, and is accompanied by confusion as an essential component; this should be suspected from the initial or early Glasgow Coma Scale score (13-14/15) if not directly recorded by clinical staff. PTA by itself is only one of several indices of severity of TBI. The nature of the head injury, including observers' accounts, clinical and neuroimaging data, the possible role of other external injuries, blood loss, acute stress disorder and the potential for hypoxic brain injury, must be taken into account as well as concomitant alcohol or substance abuse, and systemic shock. A plausible mechanism for a TBI must be demonstrable, and other causes of amnesia excluded. PMID- 26888961 TI - Sex differences in symptom severity and clusters in patients with stage C4 and stage C5 chronic venous disease. AB - BACKGROUND: Multiple symptoms associated with chronic venous disease (CVD) are poorly understood, under-recognized, and ill-managed. AIMS: The aim of this study was to determine whether there are differences in symptoms and symptom clusters between men and women with stage C4 and stage C5 CVD. METHODS: Data were collected via interviews with 264 patients using a demographic survey and an 11 item VEINES-SYM questionnaire. ANALYSIS: An intrinsic scoring algorithm was developed to calculate the overall t scores for each item by sex. Exploratory factor analysis identified symptom clusters using oblique rotation to account for correlations between factors. RESULTS: The average age was 61.7 years; 54.5% of the patients were women, 58% were African American or black, and 60.6% had diabetes. The top three symptoms for women in order of frequency were achy legs, swelling, and pain; for men, these were swelling, achy legs, and heavy legs. For the total group, two symptom clusters emerged: distressful and discomfort. There was no statistically significant difference in factor score between the sexes. Different factor loadings for symptom clusters were observed: women reported hurting and annoying clusters; and men reported nagging and irritating clusters. CONCLUSION: The data suggest differences in CVD symptoms and clusters by sex. Symptoms in the two clusters were different; however, there was consistency in the factors associated with each cluster. Co-morbid conditions and sex differences in pain responses may play a part in symptom presentation. This study supports the need for increased sex-delineated clinical assessment and consideration of the potential differences between the sexes in the management of CVD symptoms. PMID- 26888960 TI - Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. AB - Idiopathic intracranial hypertension (IIH) is a rare but important disease associated with significant morbidity. There is an expected rise in prevalence in line with the escalating global burden of obesity. Modern revisions in the terminology and diagnostic criteria for IIH help guide clinicians in investigations and researchers in standardising recruitment criteria for clinical trials. The pathophysiology of IIH is incompletely characterised; suggested underpinning mechanisms include the role of cerebrospinal fluid regulation as well as metabolic and endocrinological perspectives. Recent treatment trials are providing insights into the management but debate still surrounds key areas in treatment. This review will provide an up-to-date discussion on the potential pathogenic mechanisms and management of IIH. PMID- 26888962 TI - Combined effect of left ventricular ejection fraction and post-cardiac depressive symptoms on major adverse cardiac events after successful primary percutaneous coronary intervention: a 12-month follow-up. AB - BACKGROUND: Despite the technical advancement of percutaneous coronary intervention, major adverse cardiac events after percutaneous coronary intervention are still a critical issue in Korea as well as in western society. Recently, low left ventricular ejection fraction and depressive symptoms have been regarded as independent predictors of adverse outcomes after successful primary percutaneous coronary intervention. However, there are few studies on the combined effect of left ventricular ejection fraction at baseline and post cardiac depressive symptoms on major adverse cardiac events after percutaneous coronary intervention. AIM: The aim of the current study is to examine the combined effect of low left ventricular ejection fraction and post-cardiac depressive symptoms on major adverse cardiac events after successful primary percutaneous coronary intervention. METHODS: A total of 221 patients who underwent successful percutaneous coronary intervention were assessed for left ventricular ejection fraction and depressive symptoms at baseline and 1 month after discharge, using the patient health questionnaire 9. Major adverse cardiac event-free survival rates during the 12-month follow-up period were analysed by Kaplan-Meier survival curves and Cox proportional hazard regression methods. RESULTS: We found that the combined effect of baseline left ventricular ejection fraction less than 60% and depressive symptoms at 1 month after discharge were significantly correlated with increased incidence of major adverse cardiac events after successful primary percutaneous coronary intervention (hazard ratio 4.049; 95% confidence interval 1.365-12.011) after adjusting for sex, high sensitivity C reactive protein, depressive symptoms at baseline and comorbidity. CONCLUSIONS: Our results suggest that healthcare professionals should be aware of the necessity of early screening for post-cardiac depressive symptoms after discharge in percutaneous coronary intervention patients with a low left ventricular ejection fraction. PMID- 26888963 TI - "Two-coil technique" for embolization of small internal carotid artery aneurysms incorporating the origin of the anterior choroidal artery. AB - PURPOSE: The purpose of this article is to evaluate the efficacy, safety and stability of the "two-coil technique." MATERIALS AND METHODS: We evaluated a single-center experience by using a two-coil technique, which is a variation of the multiple-microcatheter technique in the treatment of a small internal carotid artery aneurysm with its sac incorporated with the origin of the anterior choroidal artery. Six consecutive patients with small ICA aneurysms with its sac incorporated with origin of the anterior choroidal artery and treated with the two-coil technique were included in this study. We finished the embolization with only two coils introduced via two different microcatheters without any other device assistance in all cases. Embolization status was determined at immediate postoperative and follow-up angiography after six months. RESULTS: The two-coil technique was technically successful in five of six cases; one case was converted to surgical clipping because of persistent occlusion of the anterior choroidal artery after several attempts. On follow-up study, all five cases showed stable occlusion status without recanalization or residual aneurysm. CONCLUSIONS: The two-coil technique has potential to be used for coiling small aneurysms, particularly where there is an important branch incorporated into the sac or neck of the aneurysm. PMID- 26888965 TI - Racial and Ethnic Disparities in Preventive Care: An Analysis of Routine Physical Examination Among Adolescents, 1998-2010. AB - Routine health care plays a central role in health promotion and disease prevention for children and in reducing health disparities. The purpose of this study is to examine the prevalence of routine physical examination among racially and ethnically diverse adolescents at 5 different time points. The study used data from the Minnesota Student Survey. Measures include frequency of physical examination by race/ethnicity, poverty status, and family structure. The analytic sample included 351 510 adolescents (1998, n = 67 239; 2001, n = 69 177; 2004, n = 71 084; 2007, n = 72 312; and 2010, n = 71 698). There were significant differences by racial/ethnic group at each time point. For example, in 2010, never having a physical examination was reported by 9.2% American Indian, 8.7% Asian American/Pacific Islander, 7.0% Hispanic/Latino, 4.3% Black/African American, 3.7% mixed race, and 2.6% of White respondents ( P < .001). Patterns of association emerged when the measure of routine physical examination was stratified by poverty and family structure. PMID- 26888964 TI - Src kinases central to T-cell receptor signaling regulate TLR-activated innate immune responses from human T cells. AB - TLRs have a fundamental role in immunity. We have recently reported that stimulation of TLR2 and TLR5 in freshly isolated and activated human T cells with microbial ligands without concomitant activation through the TCR brings about secretion of neutrophil chemoattractant, CXCL8, and effector cytokine, IFN-gamma, respectively. However, the mechanism of TLR signaling in T cells has not been worked out. Here, we show that the Src family kinases, p56(lck)(Lck) and p59(fyn)(Fyn), which are essential for activation of T cells through the TCR, are also critical for signal transduction through TLRs in human T cells. The secretion of CXCL8 following stimulation of the model human T cell line, Jurkat, with the TLR5 ligand, flagellin, was reduced in presence of the Src-kinase inhibitor, PP2 and specific inhibitors of Lck and Fyn. These inhibitors suppressed generation of activated JNK and p38, which were both required for TLR induced CXCL8 production. The Lck-deficient derivative of Jurkat, JCam1.6, responded poorly to TLR2, TLR5 and TLR7 agonists, and did not generate active signaling intermediates. Lck and Fyn inhibitors also reduced TLR5-induced IFN gamma secretion from the activated T cell phenotype-representing T cell line, HuT78, without modulating JNK and p38 activation. These results reveal that TCR and TLRs share key proximal signaling regulators in T cells. PMID- 26888966 TI - Systematic review of the prevalence of mental illness stigma within the Greek culture. AB - BACKGROUND: A number of primary studies have now assessed mental illness stigma within the Greek culture. A synthesis and appraisal of all available evidence is now required and will contribute to our growing understanding of the relationship between the cultural context and the formation of stigmatising attitudes. AIM: To systematically review the prevalence of mental illness public stigma within the Greek and Greek Cypriot culture. METHOD: Empirical articles with primary data pertaining to the prevalence of mental illness public stigma among Greek and/or Greek Cypriot populations were retrieved. Included studies were assessed for quality and extracted data were narratively synthesised. RESULTS: A total of 18 studies met the inclusion criteria. Methodological quality was highly variable; only 1 study was adequately statistically powered, 10 studies employed at least some element of probability sampling and obtained response rates of at least 70%, while 10 and 13 studies employed reliable and validated prevalence tools, respectively. Studies sampled the general population (n = 11), students (n = 4), healthcare professionals (n = 2), police officers, employers and family members (all n = 1). Stigma was consistently identified in moderate and high proportions across all of these groups, particularly in terms of social discrimination and restrictiveness, social distance and authoritarianism. However, some evidence of benevolence and positivity towards high-quality social care was also identified. CONCLUSION: The review highlights the wide-scale prevalence of mental illness stigma within the Greek culture and the need for further rigorous research including culturally tailored stigma interventions. PMID- 26888967 TI - Intimate partner violence-related experiences and mental health among college students in Japan, Singapore, South Korea and Taiwan. AB - BACKGROUND: Intimate partner violence (IPV) is a significant public health threat that contributes to a wide range of mental and physical health problems for victims. AIMS: The purpose of this study was to examine IPV-related experiences and mental health outcomes among college students in Japan, Singapore, South Korea and Taiwan. METHODS: The data were obtained from the Inter-University Consortium for Political and Social Research (ICPSR), the International Dating Violence Study (IDVS) 2001-2006 (ICPSR 29583; N = 981; Japan n = 207; Singapore n = 260; South Korea n = 256; Taiwan n = 258). RESULTS: Co-experience of physical IPV victimization and perpetration was associated with borderline personality traits and posttraumatic stress disorder (PTSD), but not with depression. Childhood sexual abuse, gender hostility and violence socialization were significant predictors of borderline personality traits, depression and PTSD. While country and gender variations in mental health are noted, there are two specific populations that may need special attention for mental health interventions: Taiwanese women especially for borderline personality traits and PTSD, and Japanese men especially for depression. CONCLUSION: IPV victimization and perpetration, childhood sexual abuse, gender hostility and violence socialization have a significant impact on the mental health of college students in Japan, Singapore, South Korea and Taiwan. Since IPV and mental health are significant public health issues, research on IPV and mental health consequences of IPV victimization and perpetration in these countries should be further expanded in order to better understand the interventions that will be effective in treating victims, perpetrators and victim/perpetrators of IPV. PMID- 26888968 TI - Cholesterol-Loaded Cyclodextrin Increases the Cholesterol Content of Goat Sperm to Improve Cold and Osmotic Resistance and Maintain Sperm Function after Cryopreservation. AB - The success of semen cryopreservation depends on sperm membrane integrity and function after thawing. Cholesterol-loaded cyclodextrin (CLC) is used for in vitro incorporation of cholesterol to protect cells against cold temperatures. We hypothesized that CLC treatment also enhances sperm cholesterol content to increase tolerance to osmotic shock and cryoresistance, thereby improving fertility. We confirmed the fact that treatment of goat semen with 3 mg/ml CLC increases sperm cholesterol content using both the Liebermann-Burchard approach and filipin III labeling of membrane cholesterol. Sperm were then treated with or without CLC and cryopreserved. After thawing, sperm cholesterol dramatically fell, even in the presence of CLC, which explains the mechanism of cryocapacitation. CLC treatment, however, maintained a normal prefreeze cholesterol level in sperm after cryopreservation. Furthermore, fresh sperm treated with CLC and subjected to either cold shock or incubated in hypo-, iso-, and hyperosmotic media, designed to mimic stresses associated with freezing/thawing, displayed increased temperature and osmotic tolerance. CLC treatment also improved sperm viability, motility, and acrosome integrity after thawing. Furthermore, CLC treatment did not affect the sperm's ability to undergo in vitro capacitation according to chlortetracycline fluorescence and protein tyrosine phosphorylation. A pilot field trial demonstrated that artificial insemination with sperm that underwent increased cholesterol levels following CLC treatment yielded higher fertility ( ITALIC! P< 0.1) and proliferation ( ITALIC! P< 0.05) rates in vivo than untreated semen from the same ejaculate samples. These observations suggest that CLC treatment could be used to improve cryoprotection during the freezing and thawing of goat sperm. PMID- 26888969 TI - Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis. AB - Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease. PMID- 26888970 TI - The Polycomb Group Protein EZH2 Impairs DNA Damage Repair Gene Expression in Human Uterine Fibroids. AB - Uterine fibroids are benign, smooth muscle tumors that occur in approximately 70% 80% of women by age 50 yr. The cellular and molecular mechanism(s) by which uterine fibroids (UFs) develop are not fully understood. Accumulating evidence demonstrates that several genetic abnormalities, including deletions, rearrangements, translocations, as well as mutations, have been found in UFs. These genetic anomalies suggest that low DNA damage repair capacity may be involved in UF formation. The objective of this study was to determine whether expression levels of DNA damage repair-related genes were altered, and how they were regulated in the pathogenesis of UFs. Expression levels of DNA repair related genes RAD51 and BRCA1 were deregulated in fibroid tissues as compared to adjacent myometrial tissues. Expression levels of chromatin protein enhancer of zeste homolog 2 (EZH2) were higher in a subset of fibroids as compared to adjacent myometrial tissues by both immunohistochemistry and Western blot analysis. Treatment with an inhibitor of EZH2 markedly increased expression levels of RAD51 and BRCA1 in fibroid cells and inhibited cell proliferation paired with cell cycle arrest. Restoring the expression of RAD51 and BRCA1 by treatment with EZH2 inhibitor was dependent on reducing the enrichment of trimethylation of histone 3 lysine 27 epigenetic mark in their promoter regions. This study reveals the important role of EZH2-regulated DNA damage-repair genes via histone methylation in fibroid biology, and may provide novel therapeutic targets for the medical treatment of women with symptomatic UFs. PMID- 26888971 TI - AP@home: The Artificial Pancreas Is Now at Home. AB - In the past years the development of an artificial pancreas (AP) has made great progress and many activities are ongoing in this area of research. The major step forward made in the last years was moving the evaluation of AP systems from highly controlled experimental conditions to daily life conditions at the home of patients with diabetes; this was also the aim of the European Union-funded AP@home project. Over a time period of 5 years a series of clinical studies were performed that culminated in 2 "final studies" during which an AP system was used by patients in their home environment for 2 or 3 months without supervision by a physician, living their normal lives. Two different versions of the AP system developed within this project were evaluated. A significant improvement in glycated hemoglobin was observed during closed-loop conditions despite the fact that during the control period the patients used the best currently available therapeutic option. In addition, a "single-port AP system" was developed within the project that combines continuous glucose monitoring and insulin infusion at a single tissue site. By using such a combined device the patients not only have to carry one less device around, the number of access points through the skin is also reduced from 2 to 1. In summary, close cooperation of 12 European partners, both academic centers and industry, enabled the development and evaluation of AP systems under daily life conditions. The next step is to develop these into products in cooperation with commercial partners. PMID- 26888973 TI - Current and Next Generation Portable Screening Devices for Diabetic Retinopathy. AB - Diabetic retinopathy (DR) is the leading cause of legal blindness in the United States, and with the growing epidemic of diabetes, a global increase in the incidence of DR is inevitable, so it is of utmost importance to identify the most cost-effective tools for DR screening. Emerging technology may provide advancements to offset the burden of care, simplify the process, and provide financially responsible methods to safely and effectively optimize care for patients with diabetes mellitus (DM). We review here currently available technology, both in production and under development, for DR screening. Preliminary results of smartphone-based devices, "all-in-one" devices, and alternative technologies are encouraging, but are largely pending verification of utility when used by nonophthalmic personnel. Further research comparing these devices to current nonportable telemedicine strategies and clinical fundus examination is necessary to validate these techniques and to potentially overcome the poor compliance around the globe of current strategies for DR screening. PMID- 26888974 TI - Differential Effects of Sex Pheromone Compounds on Adult Female Sea Lamprey (Petromyzon marinus) Locomotor Patterns. AB - Synchronization of male and female locomotor activity plays a critical role in ensuring reproductive success, especially in semelparous species. The goal of this study was to elucidate the effects of individual chemical signals, or pheromones, on the locomotor activity in the sea lamprey (Petromyzon marinus). In their native habitat, adult preovulated females (POF) and ovulated females (OF) are exposed to sex pheromone compounds that are released from spermiated males and attract females to nests during their migration and spawning periods. In this study, locomotor activity of individual POF and OF was measured hourly in controlled laboratory conditions using an automated video-tracking system. Differences in the activity between a baseline day (no treatment exposure) and a treatment day (sex pheromone compound or control exposure) were examined for daytime and nighttime periods. Results showed that different pheromone compound treatments affected both POF and OF sea lamprey (p < 0.05) but in different ways. Spermiated male washings (SMW) and one of its main components, 7alpha,12alpha,24 trihydroxy-5alpha-cholan-3-one 24 sulfate (3kPZS), decreased activity of POF during the nighttime. SMW also reduced activity in POF during the daytime. In contrast, SMW increased activity of OF during the daytime, and an additional compound found in SMW, petromyzonol sulfate (PZS), decreased the activity during the nighttime. In addition, we examined factors that allowed us to infer the overall locomotor patterns. SMW increased the maximum hourly activity during the daytime, decreased the maximum hourly activity during the nighttime, and reduced the percentage of nocturnal activity in OF. Our findings suggest that adult females have evolved to respond to different male compounds in regards to their locomotor activity before and after final maturation. This is a rare example of how species-wide chemosensory stimuli can affect not only the amounts of activity but also the overall locomotor pattern in a vertebrate species. PMID- 26888972 TI - Automated Diabetic Retinopathy Screening and Monitoring Using Retinal Fundus Image Analysis. AB - BACKGROUND: Diabetic retinopathy (DR)-a common complication of diabetes-is the leading cause of vision loss among the working-age population in the western world. DR is largely asymptomatic, but if detected at early stages the progression to vision loss can be significantly slowed. With the increasing diabetic population there is an urgent need for automated DR screening and monitoring. To address this growing need, in this article we discuss an automated DR screening tool and extend it for automated estimation of microaneurysm (MA) turnover, a potential biomarker for DR risk. METHODS: The DR screening tool automatically analyzes color retinal fundus images from a patient encounter for the various DR pathologies and collates the information from all the images belonging to a patient encounter to generate a patient-level screening recommendation. The MA turnover estimation tool aligns retinal images from multiple encounters of a patient, localizes MAs, and performs MA dynamics analysis to evaluate new, persistent, and disappeared lesion maps and estimate MA turnover rates. RESULTS: The DR screening tool achieves 90% sensitivity at 63.2% specificity on a data set of 40 542 images from 5084 patient encounters obtained from the EyePACS telescreening system. On a subset of 7 longitudinal pairs the MA turnover estimation tool identifies new and disappeared MAs with 100% sensitivity and average false positives of 0.43 and 1.6 respectively. CONCLUSIONS: The presented automated tools have the potential to address the growing need for DR screening and monitoring, thereby saving vision of millions of diabetic patients worldwide. PMID- 26888975 TI - Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. AB - AIM: To determine clinical correlations to intraocular vascular endothelial growth factor A (VEGF-A) suppression times (VSTs) on the treatment of neovascular age-related macular degeneration (nAMD) with ranibizumab (Lucentis) or aflibercept (Eylea). METHODS: Seven of 89 treatment-naive nAMD eyes showed persistent choroidal neovascular membrane (CNV) activity throughout a spectral domain optical coherence tomography (SD-OCT)-driven pro re nata (PRN) regimen of intravitreal ranibizumab injections over 28+/-4 months. The treatment was switched to PRN aflibercept injections and patients were followed for another 15+/-2 months. A total of 160 aqueous humour specimens were collected before the intravitreal injections, and their VEGF-A concentrations were assayed by Luminex multiplex bead analysis (Luminex, Austin, Texas, USA). Intraocular VEGF-A concentrations were correlated to CNV activity shown by SD-OCT. RESULTS: The mean duration of suppression of VEGF-A concentrations in aqueous humour below the lower limit of quantification of our assay was 34+/-5 (26-69) days for ranibizumab and 67+/-14 (49-89) days for aflibercept (p<0.001). The percentual reduction of central retinal volume (CRV) 6 weeks after injection was higher for aflibercept compared with ranibizumab (p=0.009). The time point of clinical re activity occurred about 50% earlier than the respective VST for each ranibizumab and aflibercept. CONCLUSIONS: The VST under aflibercept treatment exceeded that under ranibizumab treatment by a factor of 2. This difference correlated with differential clinical CRV reduction 6 weeks after the respective injection. For both medications, clinical activity was found at a time point as early as 50% of the individual VST. TRIAL REGISTRATION NUMBER: NCT01213667, post-results. PMID- 26888976 TI - Scleritis associated with relapsing polychondritis. AB - AIMS: To evaluate ocular disease characteristics and successful therapeutic regimens in patients with scleritis associated with relapsing polychondritis (RP). To compare these features with those seen in patients with scleritis associated with other systemic immune-mediated diseases (SIMD). METHODS: Electronic health records of 13 scleritis patients associated with RP were analysed and compared with those of 113 scleritis patients associated with other SIMD seen at two tertiary referral centres. RESULTS: Scleritis in patients with RP was often bilateral (92.3%), diffuse (76.9%), recurrent (84.6%), sometimes with decreased vision (46.2%), anterior uveitis (38.5%), peripheral keratitis (15.4%) and ocular hypertension (30.8%). Patients with scleritis associated with RP more often had bilateral scleritis (p=0.001), necrotising scleritis (23.1%; p=0.02), recurrences (p=0.001) and decreased vision (three of the six with legal blindness; p=0.012), as compared with patients who had scleritis associated with other SIMD. Nine patients (69.2%) had one or more SIMD other than RP, including systemic vasculitis (4) or other autoimmune disease (8); they antedated RP by 9 years (range 2-21 years). Successful therapy included cyclophosphamide (5), methotrexate (3), azathioprine (3), mycophenolate mofetil (2), infliximab (2) and adalimumab (1). CONCLUSIONS: Scleritis may be the first manifestation whose study leads to the diagnosis of RP. Scleritis associated with RP is more often bilateral, necrotising, recurrent and associated with decrease of vision than scleritis associated with other SIMD. About 69.2% of patients will have an additional SIMD disorder. Scleritis associated with RP most often will require immunomodulatory therapy. Occasionally, scleritis with RP may appear while using antitumor necrosis factor alpha agents. PMID- 26888977 TI - Established and emerging ancillary techniques in management of microbial keratitis: a review. AB - Microbial keratitis is a sight-threatening condition and an ocular emergency, because of the potential for rapid progression. Intensive topical antimicrobials are the mainstay and the gold standard of treatment for microbial keratitis. However, despite appropriate diagnosis and therapy, treatment failure is still common, and can result in significant morbidity due to corneal perforation and/or scarring. For this reason, clinicians continue to seek novel treatment techniques in order to expand the armamentarium of tools available to manage microbial keratitis, and in doing so improve clinical outcomes. In this review, we examine the evidence for some established, as well as a few emerging ancillary techniques used to manage microbial keratitis. These include topical corticosteroids, corneal collagen cross-linking, intrastromal antimicrobials, amniotic membrane transplantation and miscellaneous other techniques. Of these, collagen cross linking shows some promise for selected cases of infectious keratitis, although more research in the area is required before it is accepted as mainstream treatment for this potentially blinding condition. PMID- 26888978 TI - Clocks for all seasons: unwinding the roles and mechanisms of circadian and interval timers in the hypothalamus and pituitary. PMID- 26888981 TI - Dorsal horn circuitry: Complexity and implications for mechanisms of neuropathic pain. PMID- 26888980 TI - Multiple sclerosis prevalence in the United States commercially insured population. AB - OBJECTIVE: To estimate the US commercially insured multiple sclerosis (MS) annual prevalence from 2008 to 2012. METHODS: The study was a retrospective analysis using PharMetrics Plus, a nationwide claims database for over 42 million covered US representative lives. Annual point prevalence required insurance eligibility during an entire year. Our primary annual MS identification algorithm required 2 inpatient claims coded ICD-9 340 or 3 outpatient claims coded ICD-9 340 or 1 MS indicated disease-modifying therapy claim. Age-adjusted annual prevalence estimates were extrapolated to the US population using US Census data. RESULTS: The 2012 MS prevalence was 149.2 per 100,000 individuals (95% confidence interval 147.6-150.9). Prevalence was consistent over 2008-2012. Female participants were 3.13 times more likely to have MS. The highest prevalence was in participants aged 45-49 years (303.5 per 100,000 individuals [295.6-311.5]). The East Census region recorded the highest prevalence (192.1 [188.2-196.0]); the West Census region recorded the lowest prevalence (110.7 [105.5-116.0]). The US annual 2012 MS extrapolated population was 403,630 (387,445-419,833). CONCLUSIONS: MS prevalence rates from a representative commercially insured database were higher than or consistent with prior US estimates. For further accuracy improvement of US prevalence estimates, results should be confirmed after validation of MS identification algorithms, and should be expanded to other US populations, including the government-insured and the uninsured. PMID- 26888979 TI - Reducing low birth weight: prioritizing action to address modifiable risk factors. AB - Background: Low birth weight (LBW) affects 6.9% of all UK births and has remained largely unchanged for many years. The United Nations and the World Health Assembly have set targets to substantially reduce global incidence. Understanding the contribution of modifiable risk factors to the burden of LBW is required to ensure appropriate interventions are in place to achieve this reduction. Methods: Data from published studies on the risks from key modifiable factors were used alongside prevalence data from the Welsh population to calculate the population attributable risk for each factor individually and in combination. Results: Fourteen risk factors accounted for nearly half of LBW births, and 60% of those to younger mothers (<25 years). Tobacco smoke exposure was the largest contributor. We estimated that smoking in pregnancy was a factor in one in eight LBW births, increasing to one in five for women aged under 25. Conclusions: Risk factors are interrelated and inequitably distributed within the population. Exposure to one factor increases the likelihood of exposure to a constellation of factors further increasing risk. Action to address LBW must consider groups where the risk factors are most prevalent and address these risk factors together using multi-component interventions. PMID- 26888982 TI - Stage-dependent loss of cortical gyrification as Parkinson disease "unfolds". AB - OBJECTIVE: Nigrostriatal terminal losses are known to progress most rapidly in early-stage Parkinson disease (PD) and then plateau, whereas cortical pathology continues and may provide a better marker of PD progression in later stages. We investigated cortical gyrification indices in patients with different durations of PD, since cortical folding may capture complex processes involving transverse forces of neuronal sheets or underlying axonal connectivity. METHODS: Longitudinal cohort structural MRI were obtained at baseline, 18 months, and 36 months from 70 patients with PD without dementia and 70 control participants. Cortical local gyrification index (LGI) was compared between controls and PD subgroups based upon duration of illness (DOI, <1 year [PDE, n = 17], 1-5 years [PDM, n = 19], >5 years [PDL, n = 24]) and adjusted using false discovery rate. Associations between LGI and clinical measurements were assessed using multiple linear regression. Areas having significantly reduced LGI also were analyzed using baseline data from a newly established cohort (PD n = 87, control n = 66) to validate our findings. RESULTS: In the longitudinal cohort, PDL had significantly reduced overall gyrification, and bilaterally in the inferior parietal, postcentral, precentral, superior frontal, and supramarginal areas, compared to controls (p < 0.05). Longitudinally, loss of gyrification was accelerated in PDM participants, compared to controls. LGI showed robust correlations with DOI and also was correlated with PD-related clinical measurements. Similar results were obtained in the validation sample. CONCLUSIONS: Loss of cortical gyrification may be accelerated within the first few years after PD diagnosis, and become particularly prominent in later stages. Thus, it may provide a metric for monitoring progression in vivo. PMID- 26888983 TI - Structural network efficiency predicts conversion to dementia. AB - OBJECTIVE: To examine whether structural network connectivity at baseline predicts incident all-cause dementia in a prospective hospital-based cohort of elderly participants with MRI evidence of small vessel disease (SVD). METHODS: A total of 436 participants from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC), a prospective hospital-based cohort of elderly without dementia with cerebral SVD, were included in 2006. During follow up (2011-2012), dementia was diagnosed. The structural network was constructed from baseline diffusion tensor imaging followed by deterministic tractography and measures of efficiency using graph theory were calculated. Cox proportional regression analyses were conducted. RESULTS: During 5 years of follow-up, 32 patients developed dementia. MRI markers for SVD were strongly associated with network measures. Patients with dementia showed lower total network strength and global and local efficiency at baseline as compared with the group without dementia. Lower global network efficiency was independently associated with increased risk of incident all-cause dementia (hazard ratio 0.63, 95% confidence interval 0.42-0.96, p = 0.032); in contrast, individual SVD markers including lacunes, white matter hyperintensities volume, and atrophy were not independently associated. CONCLUSIONS: These results support a role of network disruption playing a pivotal role in the genesis of dementia in SVD, and suggest network analysis of the connectivity of white matter has potential as a predictive marker in the disease. PMID- 26888984 TI - Comment: Network disruption as a common framework for factors contributing to dementia. PMID- 26888988 TI - 10-Second heart rate variability and cognitive function in old age. AB - OBJECTIVE: To investigate the cross-sectional and longitudinal associations of 10 second heart rate variability (HRV) with various domains of cognitive function in older participants at risk of cardiovascular disease. METHODS: We studied 3,583 participants, mean age of 75.0 years, who were enrolled in the Prospective Study of Pravastatin in the Elderly at Risk. From baseline 10-second ECGs, standard deviation of normal-to-normal intervals was calculated as the index of HRV. Four cognitive domains were assessed at baseline and repeated during a mean follow-up period of 3.2 years. RESULTS: Lower HRV at baseline was associated with worse performance in reaction time (mean difference between low third vs high third of HRV = 1.96 seconds, 95% confidence interval [CI] 0.20 to 3.71) and processing speed (-0.57 digits coded, 95% CI -1.09 to -0.05). During follow-up, participants with lower HRV had a steeper decline in processing speed (mean annual change between low third vs high third of HRV = -0.16 digits coded, 95% CI -0.28 to 0.04). There was no difference in annual changes of reaction time or immediate and delayed memory among HRV thirds during follow-up. All these associations remained unchanged after adjustment for medications, cardiovascular risk factors, and comorbidities. CONCLUSIONS: Participants with lower 10-second HRV have worse performance in reaction time and processing speed and experience steeper decline in their processing speed, independent of medications, cardiovascular risk factors, and comorbidities. PMID- 26888987 TI - Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy. AB - OBJECTIVE: To explore the value of nuclear magnetic resonance (NMR) and functional assessments for follow-up of ambulatory and nonambulatory patients with Duchenne muscular dystrophy (DMD). METHODS: Twenty-five 53-skippable patients with DMD were included in this study; 15 were nonambulatory at baseline. All patients underwent clinical and functional assessments every 6 months using the Motor Function Measure (MFM), hand grip and key pinch strength, MoviPlate, and NMR spectroscopy and imaging studies. RESULTS: Upper limb distal strength decreased in nonambulatory patients over the period of 1 year; ambulatory patients showed improvement during the same period. The same applied for several NMRS indices, such as phosphocreatine/adenosine triphosphate, which decreased in older patients but increased in younger ambulatory patients. Fat infiltration in the upper limbs increased linearly with age. Almost all NMR and functional assessment results correlated. CONCLUSIONS: Our results underscore complementarity of functional and NMR assessments in patients with DMD. Sensitivity to change of various indices may differ according to disease stage. PMID- 26888986 TI - The challenge of comorbidity in clinical trials for multiple sclerosis. AB - OBJECTIVE: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). METHODS: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. RESULTS: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. CONCLUSION: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions. PMID- 26888989 TI - How best to obtain consent to thrombolysis: Individualized decision-making. AB - OBJECTIVE: To investigate the factors that influence the preferences of patients and their proxies concerning thrombolytic therapy and to determine how best to convey information. METHODS: A total of 613 participants were randomly assigned to a positively or negatively framed group. Each participant completed a series of surveys. We applied latent class analysis (LCA) to explore participants' patterns of choices of thrombolysis and to classify the participants into different subgroups. Then we performed regression analyses to investigate predictors of classification of the participants into each subgroup and to establish a thrombolytic decision-making model. RESULTS: LCA indicated an optimal 3-subgroup model comprising intermediate, favorable to thrombolysis, and aversion to thrombolysis subgroups. Multiple regression analysis revealed that 10 factors predicted assignment to the intermediate subgroup and 4 factors predicted assignment to the aversion to thrombolysis subgroup compared with the favorable to thrombolysis subgroup. The chi(2) tests indicated that the information presentation format and the context of thrombolysis influenced participants' choices of thrombolysis and revealed a framing effect in different subgroups. CONCLUSIONS: The preference for thrombolysis was influenced by the positive vs negative framing scenarios, the format of item presentation, the context of thrombolysis, and individual characteristics. Inconsistent results may be due to participant heterogeneity and the evaluation of limited factors in previous studies. Based on a decision model of thrombolysis, physicians should consider the effects of positive vs negative framing and should seek a neutral tone when presenting the facts, providing an important reference point for health persuasion in other clinical domains. PMID- 26888990 TI - A new scale for prognostication in Parkinson disease: Of animals and men. PMID- 26888992 TI - Real-world cost-effectiveness of pharmacogenetic screening for epilepsy treatment. AB - OBJECTIVE: To assess the cost-effectiveness of the HLA-B*15:02 screening policy for the treatment of epilepsy in Hong Kong. METHODS: From all public hospitals and clinics in Hong Kong, 13,231 patients with epilepsy who started their first antiepileptic drug (AED) between September 16, 2005, and September 15, 2011 (3 years before and 3 years after policy implementation on September 16, 2015), were identified retrospectively. A decision tree model was constructed to incorporate the real-world data on AED prescription patterns, incidences of AED-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), costs of AED treatments, SJS/TEN treatment, and HLA-B*15:02 testing, and quality of life. Cost effectiveness of the screening policy was analyzed for 3 scenarios: (1) current real-world situation, (2) "ideal" situation assuming full policy adherence and preferable testing practices, and (3) "extended" situation simulating the extension of HLA-B*15:02 screening to phenytoin in ideal practice. RESULTS: The current screening policy was associated with an incremental cost-effectiveness ratio of US $85,697 per quality-adjusted life year (QALY) compared with no screening. The incremental cost-effectiveness ratio was estimated to be US $11,090/QALY in the ideal situation and US $197,158/QALY in the extended situation. CONCLUSIONS: The HLA-B*15:02 screening policy, as currently practiced, is not cost-effective. Its cost-effectiveness may be improved by enhancing policy adherence and by low-cost point-of-care genotyping. Extending the screening to phenytoin would not be cost-effective because of the low incidence of phenytoin SJS/TEN among HLA-B*15:02 carriers. PMID- 26888991 TI - Development and external validation of a prognostic model in newly diagnosed Parkinson disease. AB - OBJECTIVE: To develop a prognostic model to predict disease outcomes in individual patients with Parkinson disease (PD) and perform an external validation study in an independent cohort. METHODS: Model development was done in the Comorbidity and Aging in Rehabilitation Patients: The Influence on Activities (CARPA) cohort (Netherlands). External validation was performed using the Cambridgeshire Parkinson's Incidence from GP to Neurologist (CamPaIGN) cohort (UK). Both are longitudinal incident cohort studies that prospectively followed up patients with PD from the time of diagnosis. A composite outcome measure was made in which patients were classified as having an unfavorable prognosis when they had postural instability or dementia at the 5-year assessment (or at the last assessment before loss to follow-up), or had died before this time. The final model was derived with a backward selection strategy from candidate predictor variables that were measured at baseline. RESULTS: In the resulting model, higher patient age, higher Unified Parkinson's Disease Rating Scale motor examination axial score, and a lower animal fluency score were all associated with a higher probability of an unfavorable outcome. External validation confirmed good discriminative ability between favorable and unfavorable outcomes with an area under the receiver operating characteristic curve of 0.85 (95% confidence interval 0.77-0.93) and a well-calibrated model with a calibration slope of 1.13 and no significant lack of fit (Hosmer-Lemeshow test: p = 0.39). CONCLUSION: We constructed a model that allows individual patient prognostication at 5 years from diagnosis, using a small set of predictor variables that can easily be obtained by clinicians or research nurses. PMID- 26888994 TI - Metabotropic glutamate receptor type 1 autoimmunity: Clinical features and treatment outcomes. AB - OBJECTIVE: To describe retrospectively the clinical associations of immunoglobulin G (IgG) targeting metabotropic glutamate receptor 1 (mGluR1-IgG). METHODS: Specimens of 9 patients evaluated on a service basis in the Mayo Clinic Neuroimmunology Laboratory by tissue-based immunofluorescence assay (IFA) yielded a robust, synaptic immunostaining pattern consistent with mGluR1-IgG (serum, 9; CSF, 2 available). Transfected HEK293 cell-based assay (CBA) confirmed mGluR1 specificity in all 11 specimens. A further 2 patients were detected in Germany primarily by CBA. RESULTS: The median symptom onset age for the 11 patients was 58 years (range 33-81 years); 6 were male. All 9 Mayo Clinic patients had subacute onset of cerebellar ataxia, 4 had dysgeusia, 1 had psychiatric symptoms, and 1 had cognitive impairment. All were evaluated for malignancy, but only 1 was affected (cutaneous T-cell lymphoma). One developed ataxia post-herpes zoster infection. Head MRIs were generally atrophic or normal-appearing, and CSF was inflammatory in just 1 of 5 tested, though mGluR1-IgG was detected in both specimens submitted. Five patients improved (attributable to immunotherapy in 4, spontaneously in 1), 3 stabilized (attributable to immunotherapy in 2, cancer therapy in 1), and 1 progressively declined (untreated). The 2 German patients had ataxia, but fulfilled multiple sclerosis diagnostic criteria (1 relapsing remitting, 1 progressive). However, both had histories of hematologic malignancy (acute lymphocytic leukemia and mantle cell lymphoma), and had mGluR1-IgG detected in serum by CBA (weakly positive on tissue-based IFA). CONCLUSIONS: mGluR1 autoimmunity represents a treatable form of cerebellar ataxia. Dysgeusia may be a diagnostic clue. Paraneoplastic, parainfectious, or idiopathic causes may occur. PMID- 26888995 TI - Depression in ALS in a large self-reporting cohort. AB - OBJECTIVE: To report an observational study of depression in a large cohort of patients with amyotrophic lateral sclerosis (ALS), including its prevalence, associations, longitudinal course, and effect on survival. METHODS: The Patient Health Questionnaire-9 (PHQ-9) (a validated depression instrument) and other self reported measures were obtained from patients with ALS as part of routine clinical care via tablet devices using a software system (Knowledge Program). Cox proportional hazard models, linear models, mixed effects models, and logistic regression were used for statistical analyses. RESULTS: Of 1,067 patients seen over an 8-year period, 964 had at least one PHQ-9 recorded. Initially, at least moderate (PHQ-9 >= 10), moderately severe (PHQ-9 >= 15), and severe depression (PHQ-9 >= 20) were found in about 33%, 14%, and 5% of patients, respectively. Higher initial PHQ-9 was significantly predictive of mortality (hazard ratio 1.041 per increasing point, 95% confidence interval 1.018-1.065) after controlling for covariates. PHQ-9 was also associated with poorer quality of life. More advanced disease initially and pseudobulbar affect were associated with depression. In 587 patients with repeated PHQ-9 measures, worsening depression was not observed. CONCLUSION: Depression is prevalent in ALS and is associated with disease severity at initial assessment. Paradoxically, however, worsening depression is not observed during follow-up despite motor progression. Most importantly, depression has detrimental effects on survival and quality of life. Treatment of depression is recommended in ALS, although it is unknown if this would improve survival. PMID- 26888993 TI - Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies. AB - OBJECTIVE: To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. METHODS: The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. RESULTS: Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. CONCLUSIONS: Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life. PMID- 26888996 TI - Testing HLA-B*15:02: Is it worth it? PMID- 26888997 TI - Antibiotic-associated encephalopathy. AB - Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state. PMID- 26888998 TI - A. V. Hill sticks his neck out. PMID- 26888999 TI - Warm acclimation improves hypoxia tolerance in Fundulus heteroclitus. AB - Human activities are increasing both the frequency of hypoxic episodes and the mean temperature of aquatic ecosystems, but few studies have considered the possibility that acclimation to one of these stressors could improve the ability to cope with the other stressor. Here, we used Atlantic killifish, Fundulus heteroclitus, to test this hypothesis. Hypoxia tolerance was measured as time to loss of equilibrium in hypoxia (LOEhyp) at 0.4 kPa oxygen. Time to LOEhyp declined from 73.3 +/- 6.9 min at 15 degrees C to 2.6 +/- 3.8 min at 23 degrees C, and at 30 degrees C no fish could withstand this level of hypoxia. Prior acclimation to warm temperatures significantly increased time to LOEhyp. Hypoxia tolerance of the southern subspecies of killifish, F. heteroclitus heteroclitus, was greater than that of the northern subspecies, F. heteroclitus macrolepidotus, measured both as critical oxygen tension (Pcrit) and as time to LOEhyp. Warm acclimation offset the negative effects of temperature on time to LOEhyp to a similar extent in the two subspecies. Warm acclimation increased total lamellar surface area of the gill in both subspecies as a result of regression of an interlamellar cell mass (ILCM). However, differences in total lamellar surface area could not explain differences in time to LOEhyp between the subspecies, suggesting that the lower time to LOEhyp of northern fish is related to their higher routine metabolic rate. These data suggest that thermal plasticity in gill morphology can improve the capacity of this species to tolerate hypoxia, and shows how existing plasticity may help organisms to cope with the complex interacting stressors that they will encounter with increasing frequency as our climate changes. PMID- 26889001 TI - FRET analysis using sperm-activating peptides tagged with fluorescent proteins reveals that ligand-binding sites exist as clusters. AB - Long-range cellular communication between the sperm and egg is critical for external fertilization. Sperm-activating peptides (SAPs) are diffusible components of the outer layer of eggs in echinoderms, and function as chemoattractants for spermatozoa. The decapeptide named speract is the best characterized sea urchin SAP. Biochemical and physiological actions of speract have been studied with purified or chemically synthesized peptides. In this work, we prepared recombinant speract fused to a fluorescent protein (FP; FP-speract) using three color variants: a cyan (eCFP), a yellow (mVenus) and a large Stokes shift yellow (mAmetrine) FP. Although these fluorescence tags are 20 times larger than speract, competitive binding experiments using mAmetrine-speract revealed that this FP-speract has binding affinity to the receptor that is comparable (7.6 fold less) to that of non-labeled speract. Indeed, 10 nmol l(-1) eCFP-speract induces physiological sperm responses such as membrane potential changes and increases in intracellular pH and Ca(2+) concentrations similar to those triggered by 10 nmol l(-1) speract. Furthermore, FP-speract maintains its fluorescence upon binding to its receptor. Using this property, we performed fluorescence resonance energy transfer (FRET) measurements with eCFP-speract and mVenus-speract as probes and obtained a positive FRET signal upon binding to the receptor, which suggests that the speract receptor exists as an oligomer, at least as a dimer, or alternatively that a single speract receptor protein possesses multiple binding sites. This property could partially account for the positive and/or negative cooperative binding of speract to the receptor. PMID- 26889000 TI - Silicon-based plant defences, tooth wear and voles. AB - Plant-herbivore interactions are hypothesized to drive vole population cycles through the grazing-induced production of phytoliths in leaves. Phytoliths act as mechanical defences because they deter herbivory and lower growth rates in mammals. However, how phytoliths impair herbivore performance is still unknown. Here, we tested whether the amount of phytoliths changes tooth wear patterns. If confirmed, abrasion from phytoliths could play a role in population crashes. We applied dental microwear texture analysis (DMTA) to laboratory and wild voles. Lab voles were fed two pelleted diets with differing amounts of silicon, which produced similar dental textures. This was most probably due to the loss of food mechanical properties through pelletization and/or the small difference in silicon concentration between diets. Wild voles were trapped in Poland during spring and summer, and every year across a population cycle. In spring, voles feed on silica-rich monocotyledons, while in the summer they also include silica depleted dicotyledons. This was reflected in the results; the amount of silica therefore leaves a traceable record in the dental microwear texture of voles. Furthermore, voles from different phases of population cycles have different microwear textures. We tentatively propose that these differences result from grazing-induced phytolith concentrations. We hypothesize that the high amount of phytoliths in response to intense grazing in peak years may result in malocclusion and other dental abnormalities, which would explain how these silicon-based plant defences help provoke population crashes. DMTA could then be used to reconstruct vole population dynamics using teeth from pellets or palaeontological material. PMID- 26889002 TI - Underwater flight by the planktonic sea butterfly. AB - In a remarkable example of convergent evolution, we show that the zooplanktonic sea butterfly Limacina helicina 'flies' underwater in the same way that very small insects fly in the air. Both sea butterflies and flying insects stroke their wings in a characteristic figure-of-eight pattern to produce lift, and both generate extra lift by peeling their wings apart at the beginning of the power stroke (the well-known Weis-Fogh 'clap-and-fling' mechanism). It is highly surprising to find a zooplankter 'mimicking' insect flight as almost all zooplankton swim in this intermediate Reynolds number range (Re=10-100) by using their appendages as paddles rather than wings. The sea butterfly is also unique in that it accomplishes its insect-like figure-of-eight wing stroke by extreme rotation of its body (what we call 'hyper-pitching'), a paradigm that has implications for micro aerial vehicle (MAV) design. No other animal, to our knowledge, pitches to this extent under normal locomotion. PMID- 26889003 TI - Zebrafish learn to forage in the dark. AB - A large diversity of fishes struggle early in life to forage on zooplankton while under the threat of predation. Some species, such as zebrafish (Danio rerio), acquire an ability to forage in the dark during growth as larvae, but it is unclear how this is achieved. We investigated the functional basis of this foraging by video-recording larval and juvenile zebrafish as they preyed on zooplankton (Artemia sp.) under infrared illumination. We found that foraging improved with age, to the extent that 1-month-old juveniles exhibited a capture rate that was an order of magnitude greater than that of hatchlings. At all ages, the ability to forage in the dark was diminished when we used a chemical treatment to compromise the cranial superficial neuromasts, which facilitate flow sensing. However, a morphological analysis showed no developmental changes in these receptors that could enhance sensitivity. We tested whether the improvement in foraging with age could instead be a consequence of learning by raising fish that were naive to the flow of prey. After 1 month of growth, both groups foraged with a capture rate that was significantly less than that of fish that had the opportunity to learn and indistinguishable from that of fish with no ability to sense flow. This suggests that larval fish learn to use water flow to forage in the dark. This ability could enhance resource acquisition under reduced competition and predation. Furthermore, our findings offer an example of learning in a model system that offers promise for understanding its neurophysiological basis. PMID- 26889004 TI - Economic Impact of Smoke-Free Air Laws in North Dakota on Restaurants and Bars. AB - INTRODUCTION: In late 2012, North Dakota expanded its statewide smoke-free air law to cover all restaurants and bars in the state. Several North Dakota communities also had local ordinances that prohibited smoking in restaurants and bars prior to the statewide law. Previous work found no effect of the initial statewide law or several local laws on restaurant and bar sales. METHODS: Using quarterly county-level employment data from 1990 to 2014, we examined whether the expanded statewide law or pre-existing local laws were associated with significant changes in employment in restaurants and bars in North Dakota. Separate models were estimated for restaurant and bar employment using two methods of controlling for smoke-free air law coverage. RESULTS: We found no evidence of a significant association between employment in restaurants and bars in North Dakota and the expanded statewide law or pre-existing local laws. Prior employment levels in restaurants and bars and prevailing economic conditions were the main drivers of restaurant and bar employment, not smoke-free air laws. CONCLUSIONS: This study examines the economic impact of smoke-free air laws in North Dakota on restaurant and bar employment following the expansion of the statewide law in late 2012 to cover all restaurants and bars. We find no significant adverse effect of smoke-free air laws on restaurants and bars, consistent with results from previous studies conducted in North Dakota and throughout the United States. IMPLICATIONS: This study is the first to analyze the economic impact of smoke-free air laws in North Dakota on restaurant and bar employment following the 2012 expansion of the statewide law to cover all restaurants and bars. We find no evidence of a significant adverse effect of smoke-free air laws on restaurants and bars, consistent with results from previous studies conducted in North Dakota and throughout the United States. Prior employment levels and prevailing economic conditions proved to be the main drivers of restaurant and bar employment, not smoke-free air laws. PMID- 26889006 TI - Screening for drought tolerance of maize hybrids by multi-scale analysis of root and shoot traits at the seedling stage. AB - We studied the drought response of eight commercial hybrid maize lines with contrasting drought sensitivity together with the reference inbred line B73 using a non-invasive platform for root and shoot phenotyping and a kinematics approach to quantify cell level responses in the leaf. Drought treatments strongly reduced leaf growth parameters including projected leaf area, elongation rate, final length and width of the fourth and fifth leaf. Physiological measurements including water use efficiency, chlorophyll fluorescence and photosynthesis were also significantly affected. By performing a kinematic analysis, we show that leaf growth reduction in response to drought is mainly due to a decrease in cell division rate, whereas a marked reduction in cell expansion rate is compensated by increased duration of cell expansion. Detailed analysis of root growth in rhizotrons under drought conditions revealed a strong reduction in total root length as well as rooting depth and width. This was reflected by corresponding decreases in fresh and dry weight of the root system. We show that phenotypic differences between lines differing in geographic origin (African vs. European) and in drought tolerance under field conditions can already be identified at the seedling stage by measurements of total root length and shoot dry weight of the plants. Moreover, we propose a list of candidate traits that could potentially serve as traits for future screening strategies. PMID- 26889005 TI - Interactions between ethylene, gibberellins, and brassinosteroids in the development of rhizobial and mycorrhizal symbioses of pea. AB - The regulation of arbuscular mycorrhizal development and nodulation involves complex interactions between the plant and its microbial symbionts. In this study, we use the recently identified ethylene-insensitive ein2 mutant in pea (Pisum sativum L.) to explore the role of ethylene in the development of these symbioses. We show that ethylene acts as a strong negative regulator of nodulation, confirming reports in other legumes. Minor changes in gibberellin1 and indole-3-acetic acid levels in ein2 roots appear insufficient to explain the differences in nodulation. Double mutants produced by crosses between ein2 and the severely gibberellin-deficient na and brassinosteroid-deficient lk mutants showed increased nodule numbers and reduced nodule spacing compared with the na and lk single mutants, but nodule numbers and spacing were typical of ein2 plants, suggesting that the reduced number of nodules innaandlkplants is largely due to the elevated ethylene levels previously reported in these mutants. We show that ethylene can also negatively regulate mycorrhizae development when ethylene levels are elevated above basal levels, consistent with a role for ethylene in reducing symbiotic development under stressful conditions. In contrast to the hormone interactions in nodulation, ein2 does not override the effect of lk or na on the development of arbuscular mycorrhizae, suggesting that brassinosteroids and gibberellins influence this process largely independently of ethylene. PMID- 26889008 TI - NB-LRR signaling induces translational repression of viral transcripts and the formation of RNA processing bodies through mechanisms differing from those activated by UV stress and RNAi. AB - Plant NB-LRR proteins confer resistance to multiple pathogens, including viruses. Although the recognition of viruses by NB-LRR proteins is highly specific, previous studies have suggested that NB-LRR activation results in a response that targets all viruses in the infected cell. Using an inducible system to activate NB-LRR defenses, we find that NB-LRR signaling does not result in the degradation of viral transcripts, but rather prevents them from associating with ribosomes and translating their genetic material. This indicates that defense against viruses involves the repression of viral RNA translation. This repression is specific to viral transcripts and does not involve a global shutdown of host cell translation. As a consequence of the repression of viral RNA translation, NB-LRR responses induce a dramatic increase in the biogenesis of RNA processing bodies (PBs). We demonstrate that other pathways that induce translational repression, such as UV irradiation and RNAi, also induce PBs. However, by investigating the phosphorylation status of eIF2alpha and by using suppressors of RNAi we show that the mechanisms leading to PB induction by NB-LRR signaling are different from these stimuli, thus defining a distinct type of translational control and anti viral mechanism in plants. PMID- 26889007 TI - Tissue-specific root ion profiling reveals essential roles of the CAX and ACA calcium transport systems in response to hypoxia in Arabidopsis. AB - Waterlogging is a major abiotic stress that limits the growth of plants. The crucial role of Ca(2+) as a second messenger in response to abiotic and biotic stimuli has been widely recognized in plants. However, the physiological and molecular mechanisms of Ca(2+) distribution within specific cell types in different root zones under hypoxia is poorly understood. In this work, whole plant physiological and tissue-specific Ca(2+) changes were studied using several ACA (Ca(2+)-ATPase) and CAX (Ca(2+)/proton exchanger) knock-out Arabidopsis mutants subjected to waterlogging treatment. In the wild-type (WT) plants, several days of hypoxia decreased the expression of ACA8, CAX4, and CAX11 by 33% and 50% compared with the control. The hypoxic treatment also resulted in an up to 11-fold tissue-dependent increase in Ca(2+) accumulation in root tissues as revealed by confocal microscopy. The increase was much higher in stelar cells in the mature zone of Arabidopsis mutants with loss of function for ACA8, ACA11, CAX4, and CAX11 In addition, a significantly increased Ca(2+) concentration was found in the cytosol of stelar cells in the mature zone after hypoxic treatment. Three weeks of waterlogging resulted in dramatic loss of shoot biomass in cax11 plants (67% loss in shoot dry weight), while in the WT and other transport mutants this decline was only 14-22%. These results were also consistent with a decline in leaf chlorophyll fluorescence (F v/F m). It is suggested that CAX11 plays a key role in maintaining cytosolic Ca(2+) homeostasis and/or signalling in root cells under hypoxic conditions. PMID- 26889010 TI - Enhancing cytokinin synthesis by overexpressing ipt alleviated drought inhibition of root growth through activating ROS-scavenging systems in Agrostis stolonifera. AB - Drought stress limits root growth and inhibits cytokinin (CK) production. Increases in CK production through overexpression of isopentenyltransferase (ipt) alleviate drought damages to promote root growth. The objective of this study was to investigate whether CK-regulated root growth was involved in the alteration of reactive oxygen species (ROS) production and ROS scavenging capacity under drought stress. Wild-type (WT) creeping bentgrass (Agrostis stolonifera L. 'Penncross') and a transgenic line (S41) overexpressing ipt ligated to a senescence-activated promoter (SAG12) were exposed to drought stress for 21 d in growth chambers. SAG12-ipt transgenic S41 developed a more extensive root system under drought stress compared to the WT. Root physiological analysis (electrolyte leakage and lipid peroxidation) showed that S41 roots exhibited less cellular damage compared to the WT under drought stress. Roots of SAG12-ipt transgenic S41 had significantly higher endogenous CK content than the WT roots under drought stress. ROS (hydrogen peroxide and superoxide) content was significantly lower and content of total and free ascorbate was significantly higher in S41 roots compared to the WT roots under drought stress. Enzymatic assays and transcript abundance analysis showed that superoxide dismutase, catalase, peroxidase, and dehydroascorbate reductase were significantly higher in S41 roots compared to the WT roots under drought stress. S41 roots also maintained significantly higher alternative respiration rates compared to the WT under drought stress. The improved root growth of transgenic creeping bentgrass may be facilitated by CK enhanced ROS scavenging through antioxidant accumulation and activation of antioxidant enzymes, as well as higher alternative respiration rates when soil water is limited. PMID- 26889009 TI - TPR5 is involved in directional cell division and is essential for the maintenance of meristem cell organization in Arabidopsis thaliana. AB - Root growth in plants is achieved through the co-ordination of cell division and expansion. In higher plants, the radial structure of the roots is formed during embryogenesis and maintained thereafter throughout development. Here we show that the tetratricopeptide repeat domain protein TPR5 is necessary for maintaining radial structure and growth rates in Arabidopsis thaliana roots. We isolated an A. thaliana mutant with reduced root growth and determined that TPR5 was the gene responsible for the phenotype. The root growth rate of the tpr5-1 mutant was reduced to ~60% of that in wild-type plants. The radial structure was disturbed by the occurrence of occasional extra periclinal cell divisions. While the number of meristematic cells was reduced in the tpr5 mutants, the cell length in the mature portion of the root did not differ from that of the wild type, suggesting that TPR5 is required for proper cell division but dispensable for cell elongation. Expression of the TPR5-GFP fusion protein driven by the TPR5 promoter displayed fluorescence in the cytoplasm of root meristems, but not in mature root regions. DNA staining revealed that frequencies of micronuclei were increased in root meristems of tpr5 mutants. From this study, we concluded that TPR5 is involved in preventing the formation of micronuclei and is necessary for both the activity and directionality of cell division in root meristems. PMID- 26889011 TI - Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling. AB - Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a (13)CO2 labelling method, using a custom built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1 The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and (13)C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/alpha-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions. PMID- 26889012 TI - The banana fruit Dof transcription factor MaDof23 acts as a repressor and interacts with MaERF9 in regulating ripening-related genes. AB - The DNA binding with one finger (Dof) proteins, a family of plant-specific transcription factors, are involved in a variety of plant biological processes. However, little information is available on their involvement in fruit ripening. We have characterized 25 MaDof genes from banana fruit (Musa acuminata), designated as MaDof1-MaDof25 Gene expression analysis in fruit subjected to different ripening conditions revealed that MaDofs were differentially expressed during different stages of ripening. MaDof10, 23, 24, and 25 were ethylene inducible and nuclear-localized, and their transcript levels increased during fruit ripening. Moreover, yeast two-hybrid and bimolecular fluorescence complementation analyses demonstrated a physical interaction between MaDof23 and MaERF9, a potential regulator of fruit ripening reported in a previous study. We determined that MaDof23 is a transcriptional repressor, whereas MaERF9 is a transcriptional activator. We suggest that they might act antagonistically in regulating 10 ripening-related genes, including MaEXP1/2/3/5, MaXET7, MaPG1, MaPME3, MaPL2, MaCAT, and MaPDC, which are associated with cell wall degradation and aroma formation. Taken together, our findings provide new insight into the transcriptional regulation network controlling banana fruit ripening. PMID- 26889013 TI - Grain protein concentration and harvestable protein under future climate conditions. A study of 108 spring barley accessions. AB - In the present study a set of 108 spring barley (H. vulgare L.) accessions were cultivated under predicted future levels of temperature and [CO2] as single factors and in combination (IPCC, AR5, RCP8.5). Across all genotypes, elevated [CO2] (700 ppm day/night) slightly decreased protein concentration by 5%, while elevated temperature (+5 degrees C day/night) substantially increased protein concentration by 29%. The combined treatment increased protein concentration across accessions by 8%. This was an increase less than predicted from strictly additive effects of the individual treatments. Despite the increase in grain protein concentration, the decrease in grain yield at combined elevated temperature and elevated [CO2] resulted in 23% less harvestable protein. There was variation in the response of the 108 accessions, which might be exploited to at least maintain if not increase harvestable grain protein under future climate change conditions. PMID- 26889014 TI - Principles of Motor Unit Physiology Evolve With Advances in Technology. AB - Movements are generated by the coordinated activation of motor units. Recent technological advances have made it possible to identify the concurrent activity of several tens of motor units, in contrast with much smaller samples available in classic studies. We discuss how these advances in technology have enabled the development of a population perspective of how the central nervous system controls motor unit activity and thereby the forces exerted by muscles. PMID- 26889017 TI - Obesity Impacts Fever and Sickness Behavior During Acute Systemic Inflammation. AB - Obesity is reaching dramatic proportions in humans and is associated with a higher risk for cardiovascular disease, diabetes, and cognitive alterations, and a higher mortality during infection and inflammation. The focus of the present review is on the influence of obesity on the presentation of fever, sickness behavior, and inflammatory responses during acute systemic inflammation. PMID- 26889015 TI - Neural Control of Walking in People with Parkinsonism. AB - People with Parkinson's disease exhibit debilitating gait impairments, including gait slowness, increased step variability, and poor postural control. A widespread supraspinal locomotor network including the cortex, cerebellum, basal ganglia, and brain stem contributes to the control of human locomotion, and altered activity of these structures underlies gait dysfunction due to Parkinson's disease. PMID- 26889019 TI - Physiology Of Drowning: A Review. AB - Drowning physiology relates to two different events: immersion (upper airway above water) and submersion (upper airway under water). Immersion involves integrated cardiorespiratory responses to skin and deep body temperature, including cold shock, physical incapacitation, and hypovolemia, as precursors of collapse and submersion. The physiology of submersion includes fear of drowning, diving response, autonomic conflict, upper airway reflexes, water aspiration and swallowing, emesis, and electrolyte disorders. Submersion outcome is determined by cardiac, pulmonary, and neurological injury. Knowledge of drowning physiology is scarce. Better understanding may identify methods to improve survival, particularly related to hot-water immersion, cold shock, cold-induced physical incapacitation, and fear of drowning. PMID- 26889016 TI - Obesity, Asthma, and the Microbiome. AB - Obesity is a risk factor for asthma, but standard asthma drugs have reduced efficacy in the obese. Obesity alters the gastrointestinal microbial community structure. This change in structure contributes to some obesity-related conditions and also could be contributing to obesity-related asthma. Although currently unexplored, obesity may also be altering lung microbiota. Understanding the role of microbiota in obesity-related asthma could lead to novel treatments for these patients. PMID- 26889020 TI - Night shift work and incidence of diabetes in the Danish Nurse Cohort. AB - OBJECTIVES: Night shift work has been associated with poor sleep, weight gain, metabolic syndrome, which are recognised risk factor for diabetes. However, only a few studies have examined the effect of shift work on diabetes risk. Here, we study the association between shift work and incidence of diabetes in Danish nurses. METHODS: We used the Danish Nurse Cohort with 28,731 participating female nurses recruited in 1993 (19,898) or 1999 (8833), when self-reported baseline information on diabetes prevalence, lifestyle and working time were collected, and followed them in the Danish Diabetes Register for incidence of diabetes until 2013. Nurses reported whether they worked night, evening, rotating or day shifts. We analysed the association between working time and diabetes incidence using a Cox proportional hazards model adjusted for diabetes risk factors, separately with and without adjustment for body mass index (BMI) which might be an intermediate variable. RESULTS: Of 19,873 nurses who worked and were diabetes free at recruitment, 837 (4.4%) developed diabetes during 15 years of follow-up. The majority of nurses (62.4%) worked day shifts, 21.8% rotating shift, 10.1% evening and 5.5% night shifts. Compared with nurses who worked day shifts, we found statistically significantly increased risk of diabetes in nurses who worked night (1.58; 1.25 to 1.99) or evening shifts (1.29; 1.04 to 1.59) in the fully adjusted models including BMI. CONCLUSIONS: Danish nurses working night and evening shifts have increased risk for diabetes, with the highest risk associated with current night shift work. PMID- 26889018 TI - Intrauterine Growth Restriction: Hungry for an Answer. AB - Intrauterine growth restriction (IUGR) has been defined in several ways, but in general describes a condition in which the fetus exhibits poor growth in utero. This complication of pregnancy poses a significant public health burden as well as increased morbidity and mortality for the offspring. In human IUGR, alteration in fetal glucose and insulin homeostasis occurs in an effort to conserve energy and survive at the expense of fetal growth in an environment of inadequate nutrient provision. Several animal models of IUGR have been utilized to study the effects of IUGR on fetal glucose handling, as well as the postnatal reprogramming of energy metabolite handling, which may be unmasked in adulthood as a maladaptive propensity for cardiometabolic disease. This developmental programming may be mediated in part by epigenetic modification of essential regulators of glucose homeostasis. Several pharmacological therapies and nonpharmacological lifestyle modifications have shown early promise in mitigating the risk for or severity of adult metabolic phenotypes but still require further study of unanticipated and/or untoward side effects. PMID- 26889022 TI - Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor--dipeptidyl peptidase 4 (DPP4)--is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission. PMID- 26889023 TI - Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides. AB - Histo-blood group antigens (HBGAs) are important binding factors for norovirus infections. We show that two human milk oligosaccharides, 2'-fucosyllactose (2'FL) and 3-fucosyllactose (3FL), could block norovirus from binding to surrogate HBGA samples. We found that 2'FL and 3FL bound at the equivalent HBGA pockets on the norovirus capsid using X-ray crystallography. Our data revealed that 2'FL and 3FL structurally mimic HBGAs. These results suggest that 2'FL and 3FL might act as naturally occurring decoys in humans. PMID- 26889021 TI - Linear Epitopes in Vaccinia Virus A27 Are Targets of Protective Antibodies Induced by Vaccination against Smallpox. AB - Vaccinia virus (VACV) A27 is a target for viral neutralization and part of the Dryvax smallpox vaccine. A27 is one of the three glycosaminoglycan (GAG) adhesion molecules and binds to heparan sulfate. To understand the function of anti-A27 antibodies, especially their protective capacity and their interaction with A27, we generated and subsequently characterized 7 murine monoclonal antibodies (MAbs), which fell into 4 distinct epitope groups (groups I to IV). The MAbs in three groups (groups I, III, and IV) bound to linear peptides, while the MAbs in group II bound only to VACV lysate and recombinant A27, suggesting that they recognized a conformational and discontinuous epitope. Only group I antibodies neutralized the mature virion in a complement-dependent manner and protected against VACV challenge, while a group II MAb partially protected against VACV challenge but did not neutralize the mature virion. The epitope for group I MAbs was mapped to a region adjacent to the GAG binding site, a finding which suggests that group I MAbs could potentially interfere with the cellular adhesion of A27. We further determined the crystal structure of the neutralizing group I MAb 1G6, as well as the nonneutralizing group IV MAb 8E3, bound to the corresponding linear epitope-containing peptides. Both the light and the heavy chains of the antibodies are important in binding to their antigens. For both antibodies, the L1 loop seems to dominate the overall polar interactions with the antigen, while for MAb 8E3, the light chain generally appears to make more contacts with the antigen. IMPORTANCE: Vaccinia virus is a powerful model to study antibody responses upon vaccination, since its use as the smallpox vaccine led to the eradication of one of the world's greatest killers. The immunodominant antigens that elicit the protective antibodies are known, yet for many of these antigens, little information about their precise interaction with antibodies is available. In an attempt to better understand the interplay between the antibodies and their antigens, we generated and functionally characterized a panel of anti-A27 antibodies and studied their interaction with the epitope using X-ray crystallography. We identified one protective antibody that binds adjacent to the heparan sulfate binding site of A27, likely affecting ligand binding. Analysis of the antibody-antigen interaction supports a model in which antibodies that can interfere with the functional activity of the antigen are more likely to confer protection than those that bind at the extremities of the antigen. PMID- 26889024 TI - Analyses of Coronavirus Assembly Interactions with Interspecies Membrane and Nucleocapsid Protein Chimeras. AB - The coronavirus membrane (M) protein is the central actor in virion morphogenesis. M organizes the components of the viral membrane, and interactions of M with itself and with the nucleocapsid (N) protein drive virus assembly and budding. In order to further define M-M and M-N interactions, we constructed mutants of the model coronavirus mouse hepatitis virus (MHV) in which all or part of the M protein was replaced by its phylogenetically divergent counterpart from severe acute respiratory syndrome coronavirus (SARS-CoV). We were able to obtain viable chimeras containing the entire SARS-CoV M protein as well as mutants with intramolecular substitutions that partitioned M protein at the boundaries between the ectodomain, transmembrane domains, or endodomain. Our results show that the carboxy-terminal domain of N protein, N3, is necessary and sufficient for interaction with M protein. However, despite some previous genetic and biochemical evidence that mapped interactions with N to the carboxy terminus of M, it was not possible to define a short linear region of M protein sufficient for assembly with N. Thus, interactions with N protein likely involve multiple linearly discontiguous regions of the M endodomain. The SARS-CoV M chimera exhibited a conditional growth defect that was partially suppressed by mutations in the envelope (E) protein. Moreover, virions of the M chimera were markedly deficient in spike (S) protein incorporation. These findings suggest that the interactions of M protein with both E and S protein are more complex than previously thought. IMPORTANCE: The assembly of coronavirus virions entails concerted interactions among the viral structural proteins and the RNA genome. One strategy to study this process is through construction of interspecies chimeras that preserve or disrupt particular inter- or intramolecular associations. In this work, we replaced the membrane (M) protein of the model coronavirus mouse hepatitis virus with its counterpart from a heterologous coronavirus. The results clarify our understanding of the interaction between the coronavirus M protein and the nucleocapsid protein. At the same time, they reveal unanticipated complexities in the interactions of M with the viral spike and envelope proteins. PMID- 26889025 TI - Novel Feline Leukemia Virus Interference Group Based on the env Gene. AB - Feline leukemia virus (FeLV) subgroups have emerged in infected cats via the mutation or recombination of the env gene of subgroup A FeLV (FeLV-A), the primary virus. We report the isolation and characterization of a novel env gene, TG35-2, and report that the TG35-2 pseudotype can be categorized as a novel FeLV subgroup. The TG35-2 envelope protein displays strong sequence identity to FeLV-A Env, suggesting that selection pressure in cats causes novel FeLV subgroups to emerge. PMID- 26889026 TI - Single-Particle Tracking Shows that a Point Mutation in the Carnivore Parvovirus Capsid Switches Binding between Host-Specific Transferrin Receptors. AB - Determining how viruses infect new hosts via receptor-binding mechanisms is important for understanding virus emergence. We studied the binding kinetics of canine parvovirus (CPV) variants isolated from raccoons-a newly recognized CPV host-to different carnivore transferrin receptors (TfRs) using single-particle tracking. Our data suggest that CPV may utilize adhesion-strengthening mechanisms during TfR binding and that a single mutation in the viral capsid at VP2 position 300 can profoundly alter receptor binding and infectivity. PMID- 26889027 TI - The C-Terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis. AB - Accumulating data suggest that tripartite-motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of >70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae(yellow fever virus, dengue virus, and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Here, we show that TRIM56 puts a check on replication of influenza A and B viruses in cell culture but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza virus activity was independent of the E3 ligase activity, B-box, or coiled-coil domain. Rather, deletion of a 63-residue-long C-terminal-tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses. IMPORTANCE: Options to treat influenza are limited, and drug resistant influenza virus strains can emerge through minor genetic changes. Understanding novel virus-host interactions that alter influenza virus fitness may reveal new targets/approaches for therapeutic interventions. We show here that TRIM56, a tripartite-motif protein, is an intrinsic host restriction factor of influenza A and B viruses. Unlike its antiviral actions against positive strand RNA viruses, the anti-influenza virus activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56 by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56, which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies. PMID- 26889028 TI - Hepatitis E Virus (HEV) Genotype 3 Infection of Human Liver Chimeric Mice as a Model for Chronic HEV Infection. AB - Genotype 3 (gt3) hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vivo HEV studies in a human liver chimeric mouse model (uPA(+/+)Nod-SCID-IL2Rgamma(-/-)) next to the A549 cell culture system, using HEV RNA-positive EDTA-plasma, feces, or liver biopsy specimens from 8 immunocompromised patients with chronic gt3 HEV. HEV from feces- or liver-derived inocula showed clear virus propagation within 2 weeks after inoculation onto A549 cells, compared to slow or no HEV propagation of HEV RNA-positive, EDTA-plasma samples. These in vitro HEV infectivity differences were mirrored in human-liver chimeric mice after intravenous (i.v.) inoculation of selected samples. HEV RNA levels of up to 8 log IU HEV RNA/gram were consistently present in 100% of chimeric mouse livers from week 2 to week 14 after inoculation with human feces- or liver-derived HEV. Feces and bile of infected mice contained moderate to large amounts of HEV RNA, while HEV viremia was low and inconsistently detected. Mouse-passaged HEV could subsequently be propagated for up to 100 days in vitro In contrast, cell culture-derived or seronegative EDTA-plasma-derived HEV was not infectious in inoculated animals. In conclusion, the infectivity of feces-derived human HEV is higher than that of EDTA-plasma-derived HEV both in vitro and in vivo Persistent HEV gt3 infections in chimeric mice show preferential viral shedding toward mouse bile and feces, paralleling the course of infection in humans. IMPORTANCE: Hepatitis E virus (HEV) genotype 3 infections are emerging in Western countries and are of great concern for immunosuppressed patients at risk for developing chronic HEV infection. Lack of adequate model systems for chronic HEV infection hampers studies on HEV infectivity and transmission and antiviral drugs. We compared the in vivo infectivity of clinical samples from chronic HEV patients in human liver chimeric mice to an in vitro virus culture system. Efficient in vivo HEV infection is observed after inoculation with feces- and liver-derived HEV but not with HEV RNA-containing plasma or cell culture supernatant. HEV in chimeric mice is preferentially shed toward bile and feces, mimicking the HEV infection course in humans. The observed in vivo infectivity differences may be relevant for the epidemiology of HEV in humans. This novel small-animal model therefore offers new avenues to unravel HEV's pathobiology. PMID- 26889030 TI - Expression of Oncogenic Alleles Induces Multiple Blocks to Human Cytomegalovirus Infection. AB - In contrast to many viruses, human cytomegalovirus (HCMV) is unable to productively infect most cancer-derived cell lines. The mechanisms of this restriction are unclear. To explore this issue, we tested whether defined oncogenic alleles, including the simian virus 40 (SV40) T antigen (TAg) and oncogenic H-Ras, inhibit HCMV infection. We found that expression of SV40 TAg blocks HCMV infection in human fibroblasts, whereas the replication of a related herpesvirus, herpes simplex virus 1 (HSV-1), was not impacted. The earliest restriction of HCMV infection involves a block of viral entry, as TAg expression prevented the nuclear delivery of viral DNA and pp65. Subsequently, we found that TAg expression reduces the abundance of platelet-derived growth factor receptor alpha (PDGFRalpha), a host protein important for HCMV entry. Viral entry into TAg immortalized fibroblasts could largely be rescued by PDGFRalpha overexpression. Similarly, PDGFRalpha overexpression in HeLa cells markedly increased the levels of HCMV gene expression and DNA replication. However, the robust production of viral progeny was not restored by PDGFRalpha overexpression in either HeLa cells or TAg-immortalized fibroblasts, suggesting additional restrictions associated with transformation and TAg expression. In TAg-expressing fibroblasts, expression of the immediate early 2 (IE2) protein was not rescued to the same extent as that of the immediate early 1 (IE1) protein, suggesting that TAg expression impacts the accumulation of major immediate early (MIE) transcripts. Transduction of IE2 largely rescued HCMV gene expression in TAg-expressing fibroblasts but did not rescue the production of infectious virions. Collectively, our data indicate that oncogenic alleles induce multiple restrictions to HCMV replication. IMPORTANCE: HCMV cannot replicate in most cancerous cells, yet the causes of this restriction are not clear. The mechanisms that restrict viral replication in cancerous cells represent viral vulnerabilities that can potentially be exploited therapeutically in other contexts. Here we found that SV40 T antigen-mediated transformation inhibits HCMV infection at multiple points in the viral life cycle, including through inhibition of proper viral entry, normal expression of immediate early genes, and viral DNA replication. Our results suggest that the SV40 T antigen could be a valuable tool to dissect cellular activities that are important for successful infection, thereby potentially informing novel antiviral development strategies. This is an important consideration, given that HCMV is a leading cause of birth defects and causes severe infection in immunocompromised individuals. PMID- 26889029 TI - The Proteolytic Activation of (H3N2) Influenza A Virus Hemagglutinin Is Facilitated by Different Type II Transmembrane Serine Proteases. AB - Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is necessary for viral activation and infectivity. In humans and mice, members of the type II transmembrane protease family (TTSP), e.g., TMPRSS2, TMPRSS4, and TMPRSS11d (HAT), have been shown to cleave influenza virus HA for viral activation and infectivity in vitro Recently, we reported that inactivation of a single HA-activating protease gene,Tmprss2, in knockout mice inhibits the spread of H1N1 influenza viruses. However, after infection of Tmprss2 knockout mice with an H3N2 influenza virus, only a slight increase in survival was observed, and mice still lost body weight. In this study, we investigated an additional trypsin like protease, TMPRSS4. Both TMPRSS2 and TMPRSS4 are expressed in the same cell types of the mouse lung. Deletion of Tmprss4 alone in knockout mice does not protect them from body weight loss and death upon infection with H3N2 influenza virus. In contrast,Tmprss2(-/-)Tmprss4(-/-)double-knockout mice showed a remarkably reduced virus spread and lung pathology, in addition to reduced body weight loss and mortality. Thus, our results identified TMPRSS4 as a second host cell protease that, in addition to TMPRSS2, is able to activate the HA of H3N2 influenza virus in vivo IMPORTANCE: Influenza epidemics and recurring pandemics are responsible for significant global morbidity and mortality. Due to high variability of the virus genome, resistance to available antiviral drugs is frequently observed, and new targets for treatment of influenza are needed. Host cell factors essential for processing of the virus hemagglutinin represent very suitable drug targets because the virus is dependent on these host factors for replication. We reported previously that Tmprss2-deficient mice are protected against H1N1 virus infections, but only marginal protection against H3N2 virus infections was observed. Here we show that deletion of two host protease genes,Tmprss2 and Tmprss4, strongly reduced viral spread as well as lung pathology and resulted in increased survival after H3N2 virus infection. Thus, TMPRSS4 represents another host cell factor that is involved in cleavage activation of H3N2 influenza viruses in vivo. PMID- 26889033 TI - Highly Efficient CRISPR/Cas9-Mediated Cloning and Functional Characterization of Gastric Cancer-Derived Epstein-Barr Virus Strains. AB - The Epstein-Barr virus (EBV) is etiologically linked to approximately 10% of gastric cancers, in which viral genomes are maintained as multicopy episomes. EBV positive gastric cancer cells are incompetent for progeny virus production, making viral DNA cloning extremely difficult. Here we describe a highly efficient strategy for obtaining bacterial artificial chromosome (BAC) clones of EBV episomes by utilizing a CRISPR/Cas9-mediated strand break of the viral genome and subsequent homology-directed repair. EBV strains maintained in two gastric cancer cell lines (SNU719 and YCCEL1) were cloned, and their complete viral genome sequences were determined. Infectious viruses of gastric cancer cell-derived EBVs were reconstituted, and the viruses established stable latent infections in immortalized keratinocytes. While Ras oncoprotein overexpression caused massive vacuolar degeneration and cell death in control keratinocytes, EBV-infected keratinocytes survived in the presence of Ras expression. These results implicate EBV infection in predisposing epithelial cells to malignant transformation by inducing resistance to oncogene-induced cell death. IMPORTANCE: Recent progress in DNA-sequencing technology has accelerated EBV whole-genome sequencing, and the repertoire of sequenced EBV genomes is increasing progressively. Accordingly, the presence of EBV variant strains that may be relevant to EBV-associated diseases has begun to attract interest. Clearly, the determination of additional disease associated viral genome sequences will facilitate the identification of any disease-specific EBV variants. We found that CRISPR/Cas9-mediated cleavage of EBV episomal DNA enabled the cloning of disease-associated viral strains with unprecedented efficiency. As a proof of concept, two gastric cancer cell-derived EBV strains were cloned, and the infection of epithelial cells with reconstituted viruses provided important clues about the mechanism of EBV-mediated epithelial carcinogenesis. This experimental system should contribute to establishing the relationship between viral genome variation and EBV-associated diseases. PMID- 26889031 TI - Increasing Clinical Severity during a Dengue Virus Type 3 Cuban Epidemic: Deep Sequencing of Evolving Viral Populations. AB - During the dengue virus type 3 (DENV-3) epidemic that occurred in Havana in 2001 to 2002, severe disease was associated with the infection sequence DENV-1 followed by DENV-3 (DENV-1/DENV-3), while the sequence DENV-2/DENV-3 was associated with mild/asymptomatic infections. To determine the role of the virus in the increasing severity demonstrated during the epidemic, serum samples collected at different time points were studied. A total of 22 full-length sequences were obtained using a deep-sequencing approach. Bayesian phylogenetic analysis of consensus sequences revealed that two DENV-3 lineages were circulating in Havana at that time, both grouped within genotype III. The predominant lineage is closely related to Peruvian and Ecuadorian strains, while the minor lineage is related to Venezuelan strains. According to consensus sequences, relatively few nonsynonymous mutations were observed; only one was fixed during the epidemic at position 4380 in the NS2B gene. Intrahost genetic analysis indicated that a significant minor population was selected and became predominant toward the end of the epidemic. In conclusion, greater variability was detected during the epidemic's progression in terms of significant minority variants, particularly in the nonstructural genes. An increasing trend of genetic diversity toward the end of the epidemic was observed only for synonymous variant allele rates, with higher variability in secondary cases. Remarkably, significant intrahost genetic variation was demonstrated within the same patient during the course of secondary infection with DENV-1/DENV-3, including changes in the structural proteins premembrane (PrM) and envelope (E). Therefore, the dynamic of evolving viral populations in the context of heterotypic antibodies could be related to the increasing clinical severity observed during the epidemic. IMPORTANCE: Based on the evidence that DENV fitness is context dependent, our research has focused on the study of viral factors associated with intraepidemic increasing severity in a unique epidemiological setting. Here, we investigated the intrahost genetic diversity in acute human samples collected at different time points during the DENV-3 epidemic that occurred in Cuba in 2001 to 2002 using a deep-sequencing approach. We concluded that greater variability in significant minor populations occurred as the epidemic progressed, particularly in the nonstructural genes, with higher variability observed in secondary infection cases. Remarkably, for the first time significant intrahost genetic variation was demonstrated within the same patient during the course of secondary infection with DENV-1/DENV-3, including changes in structural proteins. These findings indicate that high-resolution approaches are needed to unravel molecular mechanisms involved in dengue pathogenesis. PMID- 26889032 TI - Emerging Roles of Protein Deamidation in Innate Immune Signaling. AB - Protein deamidation has been considered a nonenzymatic process associated with protein functional decay or "aging." Recent studies implicate protein deamidation in regulating signal transduction in fundamental biological processes, such as innate immune responses. Work investigating gammaherpesviruses and bacterial pathogens indicates that microbial pathogens deploy deamidases or enzyme deficient homologues (pseudoenzymes) to induce deamidation of key signaling components and evade host immune responses. Here, we review studies on protein deamidation in innate immune signaling and present several imminent questions concerning the roles of protein deamidation in infection and immunity. PMID- 26889034 TI - VP8, the Major Tegument Protein of Bovine Herpesvirus 1, Interacts with Cellular STAT1 and Inhibits Interferon Beta Signaling. AB - The UL47 gene product, VP8, is the most abundant tegument protein of bovine herpesvirus 1 (BoHV-1). Previously, we demonstrated that a UL47-deleted BoHV-1 mutant (BoHV1-DeltaUL47) exhibits 100-fold-reduced virulence in vitro and is avirulent in vivo In this study, we demonstrated that VP8 expression or BoHV-1 infection inhibits interferon beta (IFN-beta) signaling by using an IFN alpha/beta-responsive plasmid in a luciferase assay. As transducer and activator of transcription (STAT) is an essential component in the IFN-signaling pathways, the effect of VP8 on STAT was investigated. An interaction between VP8 and STAT1 was established by coimmunoprecipitation assays in both VP8-transfected and BoHV 1-infected cells. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for its interaction with STAT1. The expression of VP8 did not induce STAT1 ubiquitination or degradation. Moreover, VP8 did not reduce STAT1 tyrosine phosphorylation to downregulate IFN-beta signaling. However, the expression of VP8 or a version of VP8 (amino acids 219 to 741) that contains the STAT1-interacting domains but not the nuclear localization signal prevented nuclear accumulation of STAT1. Inhibition of nuclear accumulation of STAT1 also occurred during BoHV-1 infection, while nuclear translocation of STAT1 was observed in BoHV1-DeltaUL47-infected cells. During BoHV-1 infection, VP8 was detected in the cytoplasm at 2 h postinfection without any de novo protein synthesis, at which time STAT1 was already retained in the cytoplasm. These results suggest that viral VP8 downregulates IFN-beta signaling early during infection, thus playing a role in overcoming the antiviral response of BoHV-1 infected cells. IMPORTANCE: Since VP8 is the most abundant protein in BoHV-1 virions and thus may be released in large amounts into the host cell immediately upon infection, we proposed that it might have a function in the establishment of conditions suitable for viral replication. Indeed, while nonessential in vitro, it is critical for BoHV-1 replication in vivo In this study, we determined that VP8 plays a role in downregulation of the antiviral host response by inhibiting IFN-beta signaling. VP8 interacted with and prevented nuclear accumulation of STAT1 at 2 h postinfection in the absence of de novo viral protein synthesis. Two domains of VP8, amino acids 259 to 482 and 632 to 686, were found to be responsible for this interaction. These results provide a new functional role for VP8 in BoHV-1 infection and a potential explanation for the lack of viral replication of the UL47 deletion mutant in cattle. PMID- 26889035 TI - Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity. AB - Antibodies are implicated in long-term immunity against numerous pathogens, and because of this property, antibody induction is the basis for many vaccines. Little is known about the influence of viral persistence on the evolving antibody response. Here, we examined the characteristics of antibody responses to persistent infection by employing the prototypic betaherpesvirus family member cytomegalovirus (CMV) in experimental mouse models. During the course of infection, mouse CMV (MCMV)-specific IgM and IgG responses are elicited; however, IgG levels gradually inflate in the persistent phase of infection while IgM levels are stably maintained. Whereas CD27-CD70 interactions are dispensable, the CD28/B7 costimulatory pathway is critical for the class switching of MCMV specific IgM-to-IgG B cell responses, which corresponds to the CD28/B7-dependent formation of CD4(+)T follicular helper cells (TFH) and germinal center (GC) B cells. Furthermore, the initial viral inoculum dose dictates the height of the antibody levels during IgG antibody inflation and relates to the induction of long-lived plasma cells and memory B cells. Antibody avidity nonetheless is not altered after the establishment of viral persistence and occurs independently of the inoculum doses. However, repetitive challenge with intact viral particles, accompanied by increased GC reactivity, promotes the development of high-avidity IgG responses with neutralizing capacity. These insights can be used for the rational design of CMV-based vaccines aimed at inducing antibody responses. IMPORTANCE: Antibodies provide long-term protection to different pathogens. However, how antibody responses develop during persistent virus infection is not entirely clear. Here, we characterize factors that influence the virus-specific antibody response to persistent CMV. This study describes that during persistent infection, CMV-specific IgM antibody levels are stably maintained while IgG2b and IgG2c levels gradually inflate over time. In contrast, the IgG avidity remains similar after the establishment of viral persistence. The induction of T follicular helper cells and GC B cells requires CD4(+)T cell help and CD28/B7 costimulation signals and is essential for the development of CMV-specific IgG antibody responses. Furthermore, neutralizing CMV-specific antibodies appear to develop late after infection, yet the neutralizing capacity can be improved upon repetitive viral challenge that is associated with increased GC reactivity. The results described here could inform the use of CMV-based vaccines and may help to understand how our immune system copes with this persistent virus. PMID- 26888985 TI - Prespecified dose-response analysis for A Very Early Rehabilitation Trial (AVERT). AB - OBJECTIVE: Our prespecified dose-response analyses of A Very Early Rehabilitation Trial (AVERT) aim to provide practical guidance for clinicians on the timing, frequency, and amount of mobilization following acute stroke. METHODS: Eligible patients were aged >=18 years, had confirmed first (or recurrent) stroke, and were admitted to a stroke unit within 24 hours of stroke onset. Patients were randomized to receive very early and frequent mobilization, commencing within 24 hours, or usual care. We used regression analyses and Classification and Regression Trees (CART) to investigate the effect of timing and dose of mobilization on efficacy and safety outcomes, irrespective of assigned treatment group. RESULTS: A total of 2,104 patients were enrolled, of whom 2,083 (99.0%) were followed up at 3 months. We found a consistent pattern of improved odds of favorable outcome in efficacy and safety outcomes with increased daily frequency of out-of-bed sessions (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.09 to 1.18, p < 0.001), keeping time to first mobilization and mobilization amount constant. Increased amount (minutes per day) of mobilization reduced the odds of a good outcome (OR 0.94, 95% CI 0.91 to 0.97, p < 0.001). Session frequency was the most important variable in the CART analysis, after prognostic variables age and baseline stroke severity. CONCLUSION: These data suggest that shorter, more frequent mobilization early after acute stroke is associated with greater odds of favorable outcome at 3 months when controlling for age and stroke severity. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that shorter, more frequent early mobilization improves the chance of regaining independence after stroke. PMID- 26889037 TI - SUMO Modification Stabilizes Dengue Virus Nonstructural Protein 5 To Support Virus Replication. AB - Small ubiquitin-like modifier (SUMO) participates in a reversible posttranslational modification process (SUMOylation) that regulates a wide variety of cellular processes and plays important roles for numerous viruses during infection. However, the roles of viral protein SUMOylation in dengue virus (DENV) infection have not been elucidated. In this study, we found that the SUMOylation pathway was involved in the DENV life cycle, since DENV replication was reduced by silencing the cellular gene Ubc9, which encodes the sole E2 conjugating enzyme required for SUMOylation. By in vivo and in vitro SUMOylation assays, the DENV NS5 protein was identified as an authentic SUMO-targeted protein. By expressing various NS5 mutants, we found that the SUMO acceptor sites are located in the N-terminal domain of NS5 and that a putative SUMO-interacting motif (SIM) of this domain is crucial for its SUMOylation. A DENV replicon harboring the SUMOylation-defective SIM mutant showed a severe defect in viral RNA replication, supporting the notion that NS5 SUMOylation is required for DENV replication. SUMOylation-defective mutants also failed to suppress the induction of STAT2-mediated host antiviral interferon signaling. Furthermore, the SUMOylation of NS5 significantly increased the stability of NS5 protein, which could account for most of the biological functions of SUMOylated NS5. Collectively, these findings suggest that the SUMOylation of DENV NS5 is one of the mechanisms regulating DENV replication. IMPORTANCE: SUMOylation is a common posttranslational modification that regulates cellular protein functions but has not been reported in the proteins of dengue virus. Here, we found that the replicase of DENV, nonstructural protein 5 (NS5), can be SUMOylated. It is well known that providing RNA-dependent RNA polymerase activity and antagonizing host antiviral IFN signaling are a "double indemnity" of NS5 to support DENV replication. Without SUMOylation, NS5 fails to maintain its protein stability, which consequently disrupts its function in viral RNA replication and innate immunity antagonism. DENV threatens billions of people worldwide, but no licensed vaccine or specific therapeutics are currently available. Thus, our findings suggest that rather than specifically targeting NS5 enzyme activity, NS5 protein stability is a novel drug target on the growing list of anti-DENV strategies. PMID- 26889036 TI - A Novel Toll-Like Receptor 9 Agonist, MGN1703, Enhances HIV-1 Transcription and NK Cell-Mediated Inhibition of HIV-1-Infected Autologous CD4+ T Cells. AB - Toll-like receptor (TLR) agonists are potent enhancers of innate antiviral immunity and may also reverse HIV-1 latency. Therefore, TLR agonists have a potential role in the context of a "shock-and-kill" approach to eradicate HIV-1. Our extensive preclinical evaluation suggests that a novel TLR9 agonist, MGN1703, may indeed perform both functions in an HIV-1 eradication trial. Peripheral blood mononuclear cells (PBMCs) from aviremic HIV-1-infected donors on antiretroviral therapy (ART) that were incubated with MGN1703 ex vivo exhibited increased secretion of interferon alpha (IFN-alpha) (P= 0.005) and CXCL10 (P= 0.0005) in culture supernatants. Within the incubated PBMC pool, there were higher proportions of CD69-positive CD56(dim)CD16(+)NK cells (P= 0.001) as well as higher proportions of CD107a-positive (P= 0.002) and IFN-gamma-producing (P= 0.038) NK cells. Incubation with MGN1703 also increased the proportions of CD69 expressing CD4(+)and CD8(+)T cells. Furthermore, CD4(+)T cells within the pool of MGN1703-incubated PBMCs showed enhanced levels of unspliced HIV-1 RNA (P= 0.036). Importantly, MGN1703 increased the capacity of NK cells to inhibit virus spread within a culture of autologous CD4(+)T cells assessed by using an HIV-1 p24 enzyme-linked immunosorbent assay (ELISA) (P= 0.03). In conclusion, we show that MGN1703 induced strong antiviral innate immune responses, enhanced HIV-1 transcription, and boosted NK cell-mediated suppression of HIV-1 infection in autologous CD4(+)T cells. These findings support clinical testing of MGN1703 in HIV-1 eradication trials. IMPORTANCE: We demonstrate that MGN1703 (a TLR9 agonist currently undergoing phase 3 clinical testing for the treatment of metastatic colorectal cancer) induces potent antiviral responses in immune effector cells from HIV-1-infected individuals on suppressive antiretroviral therapy. The significantly improved safety and tolerability profiles of MGN1703 versus TLR9 agonists of the CpG-oligodeoxynucleotide (CpG-ODN) family are due to its novel "dumbbell-shape" structure made of covalently closed, natural DNA. In our study, we found that incubation of peripheral blood mononuclear cells with MGN1703 results in natural killer cell activation and increased natural killer cell function, which significantly inhibited the spread of HIV in a culture of autologous CD4(+)T cells. Furthermore, we discovered that MGN1703-mediated activation can enhance HIV-1 transcription in CD4(+)T cells, suggesting that this molecule may serve a dual purpose in HIV-1 eradication therapy: enhanced immune function and latency reversal. These findings provide a strong preclinical basis for the inclusion of MGN1703 in an HIV eradication clinical trial. PMID- 26889039 TI - Phosphorylation of Bovine Herpesvirus 1 VP8 Plays a Role in Viral DNA Encapsidation and Is Essential for Its Cytoplasmic Localization and Optimal Virion Incorporation. AB - VP8 is a major tegument protein of bovine herpesvirus 1 (BoHV-1) and is essential for viral replication in cattle. The protein undergoes phosphorylation after transcription through cellular casein kinase 2 (CK2) and a viral kinase, US3. In this study, a virus containing a mutated VP8 protein that is not phosphorylated by CK2 and US3 (BoHV-1-YmVP8) was constructed by homologous recombination in mammalian cells. When BoHV-1-YmVP8-infected cells were observed by transmission electron microscopy, blocking phosphorylation of VP8 was found to impair viral DNA encapsidation, resulting in release of incomplete viral particles to the extracellular environment. Consequently, less infectious virus was produced by the mutant virus than by wild-type (WT) virus. A comparison of mutant and WT VP8 by confocal microscopy revealed that mutant VP8 is nuclear throughout infection while WT VP8 is nuclear early during infection and is associated with the Golgi apparatus at later stages. This, together with the observation that mutant VP8 is present in virions, albeit in smaller amounts, suggests that the incorporation of VP8 may occur at two stages. The first takes place without the need for phosphorylation and before or during nuclear egress of capsids, whereas the second occurs in the Golgi apparatus and requires phosphorylation of VP8. The results indicate that phosphorylated VP8 plays a role in viral DNA encapsidation and in the secondary virion incorporation of VP8. To perform these functions, the cellular localization of VP8 is adjusted based on the phosphorylation status. IMPORTANCE: In this study, phosphorylation of VP8 was shown to have a function in BoHV-1 replication. A virus containing a mutated VP8 protein that is not phosphorylated by CK2 and US3 (BoHV-1-YmVP8) produced smaller numbers of infectious virions than wild-type (WT) virus. The maturation and egress of WT and mutant BoHV-1 were studied, showing a process similar to that reported for other alphaherpesviruses. Interestingly, lack of phosphorylation of VP8 by CK2 and US3 resulted in reduced incorporation of viral DNA into capsids during mutant BoHV-1 infection, as well as lower numbers of extracellular virions. Furthermore, mutant VP8 remained nuclear throughout infection, in contrast to WT VP8, which is nuclear at early stages and Golgi apparatus associated late during infection. This correlates with smaller amounts of mutant VP8 in virions and suggests for the first time that VP8 may be assembled into the virions at two stages, with the latter dependent on phosphorylation. PMID- 26889038 TI - Guanylate-Binding Protein 1, an Interferon-Induced GTPase, Exerts an Antiviral Activity against Classical Swine Fever Virus Depending on Its GTPase Activity. AB - Many viruses trigger the type I interferon (IFN) pathway upon infection, resulting in the transcription of hundreds of interferon-stimulated genes (ISGs), which define the antiviral state of the host. Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious viral disease endangering the pig industry in many countries. However, anti-CSFV ISGs are poorly documented. Here we screened 20 ISGs that are commonly induced by type I IFNs against CSFV in lentivirus-delivered cell lines, resulting in the identification of guanylate-binding protein 1 (GBP1) as a potent anti-CSFV ISG. We observed that overexpression of GBP1, an IFN-induced GTPase, remarkably suppressed CSFV replication, whereas knockdown of endogenous GBP1 expression by small interfering RNAs significantly promoted CSFV growth. Furthermore, we demonstrated that GBP1 acted mainly on the early phase of CSFV replication and inhibited the translation efficiency of the internal ribosome entry site of CSFV. In addition, we found that GBP1 was upregulated at the transcriptional level in CSFV-infected PK-15 cells and in various organs of CSFV-infected pigs. Coimmunoprecipitation and glutathione S-transferase (GST) pulldown assays revealed that GBP1 interacted with the NS5A protein of CSFV, and this interaction was mapped in the N-terminal globular GTPase domain of GBP1. Interestingly, the K51 of GBP1, which is crucial for its GTPase activity, was essential for the inhibition of CSFV replication. We showed further that the NS5A-GBP1 interaction inhibited GTPase activity, which was critical for its antiviral effect. Taking our findings together, GBP1 is an anti-CSFV ISG whose action depends on its GTPase activity. IMPORTANCE: Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), an economically important viral disease affecting the pig industry in many countries. To date, only a few host restriction factors against CSFV, including interferon-stimulated genes (ISGs), have been characterized. Using a minilibrary of porcine ISGs, we identify porcine guanylate-binding protein 1 (GBP1) as a potent antiviral ISG against CSFV. We further show that the anti-CSFV action of GBP1 depends on its GTPase activity. The K51 of GBP1, critical for its GTPase activity, is essential for the antiviral action of GBP1 against CSFV replication, and the binding of the NS5A protein to GBP1 antagonizes the GTPase activity and thus the antiviral effect. This study will facilitate the development of anti-CSFV therapeutic agents by targeting host factors and may provide a new strategy for the control of CSF. PMID- 26889040 TI - Molluscum Contagiosum Virus Transcriptome in Abortively Infected Cultured Cells and a Human Skin Lesion. AB - Molluscum contagiosum virus (MOCV), the only circulating human-specific poxvirus, has a worldwide distribution and causes benign skin lesions that may persist for months in young children and severe infections in immunosuppressed adults. Studies of MOCV are restricted by the lack of an efficient animal model or a cell culture replication system. We used next-generation sequencing to analyze and compare polyadenylated RNAs from abortive MOCV infections of several cell lines and a human skin lesion. Viral RNAs were detected for 14 days after MOCV infection of cultured cells; however, there was little change in the RNA species during this time and a similar pattern occurred in the presence of an inhibitor of protein synthesis, indicating a block preventing postreplicative gene expression. Moreover, a considerable number of MOCV RNAs mapped to homologs of orthopoxvirus early genes, but few did so to homologs of intermediate or late genes. The RNAs made during in vitro infections represent a subset of RNAs detected in human skin lesions which mapped to homologs of numerous postreplicative as well as early orthopoxvirus genes. Transfection experiments using fluorescent protein and luciferase reporters demonstrated that vaccinia virus recognized MOCV intermediate and late promoters, indicating similar gene regulation. The specific recognition of the intermediate promoter in MOCV infected cells provided evidence for the synthesis of intermediate transcription factors, which are products of early genes, but not for late transcription factors. Transcriptome sequencing (RNA-seq) and reporter gene assays may be useful for testing engineered cell lines and conditions that ultimately could provide an in vitro replication system. IMPORTANCE: The inability to propagate molluscum contagiosum virus, which causes benign skin lesions in young children and more extensive infections in immunosuppressed adults, has constrained our understanding of the biology of this human-specific virus. In the present study, we characterized the RNAs synthesized in abortively infected cultured cells and a human skin lesion by next-generation sequencing. These studies provided an initial transcription map of the MOCV genome, suggested temporal regulation of gene expression, and indicated that the in vitro replication block occurs prior to intermediate and late gene expression. RNA-seq and reporter assays, as described here, may help to further evaluate MOCV gene expression and define conditions that could enable MOCV replication in vitro. PMID- 26889043 TI - Splenic RNA and MicroRNA Mimics Promote Complement Factor B Production and Alternative Pathway Activation via Innate Immune Signaling. AB - Complement factor B (cfB) is an essential component of the alternative pathway (AP) and plays an important role in the pathogenesis of polymicrobial sepsis. However, the mechanism leading to cfB production and AP activation during sepsis remains poorly understood. In this study, we found that plasma cell-free RNA was significantly increased following cecal ligation and puncture (CLP), an animal model of polymicrobial sepsis, and was closely associated with sepsis severity. Quantitative RT-PCR and microRNA (miRNA) array analysis revealed an increase in bacterial RNA and multiple host miRNAs (miR-145, miR-146a, miR-122, miR-210) in the blood following CLP. Treatment with tissue RNA or synthetic miRNA mimics (miR 145, miR-146a, miR-122, miR-34a) induced a marked increase in cfB production in cardiomyocytes or macrophages. The newly synthesized cfB released into medium was biologically active because it participated in AP activation initiated by cobra venom factor. Genetic deletion of TLR7 or MyD88, but not TLR3, and inhibition of the MAPKs (JNK and p38) or NF-kappaB abolished miR-146a-induced cfB production. In vivo, CLP led to a significant increase in splenic cfB expression that correlated with the plasma RNA or miRNA levels. Peritoneal injection of RNA or miR-146a led to an increase in cfB expression in the peritoneal space that was attenuated in MyD88-knockout or TLR7-knockout mice, respectively. These findings demonstrate that host cellular RNA and specific miRNAs are released into the circulation during polymicrobial sepsis and may function as extracellular mediators capable of promoting cfB production and AP activation through specific TLR7 and MyD88 signaling. PMID- 26889041 TI - The Attenuation Phenotype of a Ribavirin-Resistant Porcine Reproductive and Respiratory Syndrome Virus Is Maintained during Sequential Passages in Pigs. AB - In a previous study, ribavirin-resistant porcine reproductive and respiratory syndrome virus (PRRSV) mutants (RVRp13 and RVRp22) were selected, and their resistance against random mutation was shown in cultured cells. In the present study, these ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability during three pig-to-pig passages in comparison with modified live virus (MLV) (Ingelvac PRRS MLV). Pigs challenged with RVRp22 had significantly lower (P< 0.05) viral loads in sera and tissues than pigs challenged with MLV or RVRp13 at the first passage, and the attenuated replication of RVRp22 was maintained until the third passage. Viral loads in sera and tissues dramatically increased in pigs challenged with MLV or RVRp13 during the second passage. Consistently, all five sequences associated with the attenuation of virulent PRRSV in RVRp13 and MLV quickly reverted to wild-type sequences during the passages, but two attenuation sequences were maintained in RVRp22 even after the third passage. In addition, RVRp22 showed a significantly lower (P< 0.001) mutation frequency in nsp2, which is one of the most variable regions in the PRRSV genome, than MLV. Nine unique mutations were found in open reading frames (ORFs) 1a, 2, and 6 in the RVRp22 genome based on full-length sequence comparisons with RVRp13, VR2332 (the parental virus of RVRp13 and RVRp22), and MLV. Based on these results, it was concluded that RVRp22 showed attenuated replication in pigs; further, because of the high genetic stability of RVRp22, its attenuated phenotype was stable even after three sequential passages in pigs. IMPORTANCE: PRRSV is a rapidly evolving RNA virus. MLV vaccines are widely used to control PRRS; however, there have been serious concerns regarding the use of MLV as a vaccine virus due to the rapid reversion to virulence during replication in pigs. As previously reported, ribavirin is an effective antiviral drug against many RNA viruses. Ribavirin-resistant mutants reemerged by escaping lethal mutagenesis when the treatment concentration was sublethal, and those mutants were genetically more stable than parental viruses. In a previous study, two ribavirin-resistant PRRSV mutants (RVRp13 and RVRp22) were selected, and their higher genetic stability was shown in vitro Consequently, in the present study, both of the ribavirin-resistant mutants were evaluated in terms of their genetic and phenotypic stability in vivo RVRp22 was found to exhibit higher genetic and phenotypic stability than MLV, and nine unique mutations were identified in the RVRp22 genome based on a full-length sequence comparison with the RVRp13, VR2332, and MLV genomes. PMID- 26889042 TI - Range of CD4-Bound Conformations of HIV-1 gp120, as Defined Using Conditional CD4 Induced Antibodies. AB - The HIV envelope binds cellular CD4 and undergoes a range of conformational changes that lead to membrane fusion and delivery of the viral nucleocapsid into the cellular cytoplasm. This binding to CD4 reveals cryptic and highly conserved epitopes, the molecular nature of which is still not fully understood. The atomic structures of CD4 complexed with gp120 core molecules (a form of gp120 in which the V1, V2, and V3 loops and N and C termini have been truncated) have indicated that a hallmark feature of the CD4-bound conformation is the bridging sheet minidomain. Variations in the orientation of the bridging sheet hairpins have been revealed when CD4-liganded gp120 was compared to CD4-unliganded trimeric envelope structures. Hence, there appears to be a number of conformational transitions possible in HIV-1 monomeric gp120 that are affected by CD4 binding. The spectrum of CD4-bound conformations has been interrogated in this study by using a well-characterized panel of conditional, CD4-induced (CD4i) monoclonal antibodies (MAbs) that bind HIV-1 gp120 and its mutations under various conditions. Two distinct CD4i epitopes of the outer domain were studied: the first comprises the bridging sheet, while the second contains elements of the V2 loop. Furthermore, we show that the unliganded extended monomeric core of gp120 (coree) assumes an intermediate CD4i conformation in solution that further undergoes detectable rearrangements upon association with CD4. These discoveries impact both accepted paradigms concerning gp120 structure and the field of HIV immunogen design. IMPORTANCE: Elucidation of the conformational transitions that the HIV-1 envelope protein undergoes during the course of entry into CD4(+)cells is fundamental to our understanding of HIV biology. The binding of CD4 triggers a range of gp120 structural rearrangements that could present targets for future drug design and development of preventive vaccines. Here we have systematically interrogated and scrutinized these conformational transitions using a panel of antibody probes that share a specific preference for the CD4i conformations. These have been employed to study a collection of gp120 mutations and truncations. Through these analyses, we propose 4 distinct sequential steps in CD4i transitions of gp120 conformations, each defined by antibody specificities and structural requirements of the HIV envelope monomer. As a result, we not only provide new insights into this dynamic process but also define probes to further investigate HIV infection. PMID- 26889044 TI - BCG Vaccination Induces Robust CD4+ T Cell Responses to Mycobacterium tuberculosis Complex-Specific Lipopeptides in Guinea Pigs. AB - A new class of highly antigenic, MHC-II-restricted mycobacterial lipopeptides that are recognized by CD4-positive T lymphocytes of Mycobacterium tuberculosis infected humans has recently been described. To investigate the relevance of this novel class of mycobacterial Ags in the context of experimental bacille Calmette Guerin (BCG) vaccination, Ag-specific T cell responses to mycobacterial lipid and lipopeptide-enriched Ag preparations were analyzed in immunized guinea pigs. Lipid and lipopeptide preparations as well as complex Ag mixtures, such as tuberculin, mycobacterial lysates, and culture supernatants, all induced a similar level of T cell proliferation. The hypothesis that lipopeptide-specific T cells dominate the early BCG-induced T cell response was corroborated in restimulation assays by the observation that Ag-expanded T cells specifically responded to the lipopeptide preparation. A comparative analysis of the responses to Ag preparations from different mycobacterial species revealed that the antigenic lipopeptides are specific for strains of the M. tuberculosis complex. Their intriguing conservation in pathogenic tuberculous bacteria and the fact that these highly immunogenic Ags seem to be actively released during in vitro culture and intracellular infection prompt the urgent question about their role in the fine-tuned interplay between the pathogen and its mammalian host, in particular with regard to BCG vaccination strategies. PMID- 26889047 TI - Marchantia: Past, Present and Future. PMID- 26889046 TI - Quantitative Proteomics Analysis Reveals the Min System of Escherichia coli Modulates Reversible Protein Association with the Inner Membrane. AB - The Min system of Escherichia coli mediates placement of the division septum at the midcell. It oscillates from pole to pole to establish a concentration gradient of the division inhibition that is high at the poles but low at the midcell; the cell middle thereby becomes the most favorable site for division. Although Min oscillation is well studied from molecular and biophysical perspectives, it is still an enigma as to whether such a continuous, energy consuming, and organized movement of the Min proteins would affect cellular processes other than the division site selection. To tackle this question, we compared the inner membrane proteome of the wild-type and Deltamin strains using a quantitative approach. Forty proteins that showed differential abundance on the inner membrane of the mutant cells were identified and defined as proteins of interest (POIs). More than half of the POIs were peripheral membrane proteins, suggesting that the Min system affects mainly reversible protein association with the inner membrane. In addition, 6 out of 10 selected POIs directly interacted with at least one of the Min proteins, confirming the correlation between POIs and the Min system.Further analysis revealed a functional relationship between metabolism and the Min system. Metabolic enzymes accounted for 45% of the POIs, and there was a change of metabolites in the related reactions. We hypothesize that the Min system could alter the membrane location of proteins to modulate their enzymatic activity. Thus, the metabolic modulation in the Deltamin mutant is likely an adaptive phenotype in cells of abnormal size and chromosome number due to an imbalanced abundance of proteins on the inner membrane. Taken together, the current work reports novel interactions of the Min system and reveals a global physiological impact of the Min system in addition to the division site placement. PMID- 26889048 TI - Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E cadherin. PMID- 26889049 TI - Assessment of quality of life of children and adolescents with cancer during their treatment. AB - OBJECTIVE: The purpose of this study was to evaluate the quality of life of children and adolescents with any type of cancer in all phases of their treatment. METHODS: Fifty-six newly diagnosed patients diagnosed with malignancy and hospitalized in a Pediatric Hematology-Oncology Unit in Athens were included in the study. Minneapolis-Manchester Quality of Life Instrument was used for data collection from July 2010 to December 2012. The assessment of children and adolescents' quality of life who were under treatment was performed in three different stages of treatment. RESULTS: The results of the study showed that the quality of life of children and adolescents with cancer did not change notably during their treatment (F = 0.16, P = 0.86 and F = 0.03, P = 0.97). For the first measurement, at the beginning of the therapy, the score on the scale for quality of life for children and adolescents was 3.44 and 3.88, respectively, in the middle of the treatment 3.36 and 3.89, respectively, and 3.43 and 3.89, respectively, when therapy was completed. Children and adolescents diagnosed with hematologic cancer stated higher quality of life scores (z = -1.61, P = 0.05 and t = 2.64, P = 0.007). Moreover, teenage patients (F = 13.22, P = 0.001) and male patients (t = 2.31, P = 0.02 and t = 2.27, P = 0.02) expressed better quality-of life scores. CONCLUSION: According to the results, children and adolescents with any kind of cancer have better quality-of-life scores at the end of their treatment, and when they are supported by their family. PMID- 26889051 TI - War on Cancer Redux. PMID- 26889045 TI - An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment. AB - Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARgamma activation via rosiglitazone (RSG) would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. In this study, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) anti-inflammatory (M2)-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared with term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL-12 but low levels of peroxisome proliferator-activated receptor gamma (PPARgamma) during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1<->M2 polarization in vitro; 6) incubation with RSG reduces the expression of TNF and IL-12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with RSG reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic proinflammatory response and downregulating mRNA and protein expression of NF-kappaB, TNF, and IL-10 in decidual and myometrial macrophages in C57BL/6J mice. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor and that PPARgamma activation via RSG can attenuate the macrophage-mediated proinflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARgamma pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. PMID- 26889050 TI - Lipoprotein apheresis to treat elevated lipoprotein (a). AB - An elevated plasma concentration of lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. Life style modification and currently available drugs either fail to effectively lower plasma Lp(a) levels or do not result in clinical benefit. However, lipoprotein apheresis is very efficient in decreasing Lp(a) concentrations. A single apheresis session can acutely decrease Lp(a) by approximately 60-75%, and apheresis performed weekly or biweekly results in considerably decreased mean interval concentrations (approximately 25-40% reduction). While most apheresis systems (heparin-induced extracorporeal LDL precipitation, direct adsorption of lipoproteins, lipoprotein apheresis with dextran-sulfate, lipid filtration, immunoadsorption) decrease LDL and Lp(a), Lipopac is specific and only decreases Lp(a). Lp(a) apheresis is expensive and time consuming, but associated with very few side effects. Two randomized controlled trials give conflicting consults with respect to the effect on angiographic changes. Retrospective analyses indicate that regular apheresis translates into clinical benefit in patients with elevated Lp(a), but adequate randomized controlled trials are lacking. PMID- 26889052 TI - Integration of Regulatory Guidelines into Protein Drug Product Development. AB - The drug product development process for proteins went through its infancy in the early eighties of last century and is in its maturity today. This has been driven largely by the rapid growth of the biotechnology industry, which led to the development and issuance of many regulatory guidelines/directories, especially those through the International Conference of Harmonization (ICH). These guidelines have certainly guided different aspects of a drug product development process. On the other hand, they were issued separately on different topics and in different time periods. An integration of all relevant guidelines into the corresponding areas in drug product development would greatly facilitate the development process. The purpose of this short review is to integrate the relevant (mainly ICH) regulatory guidelines into protein drug product development and to discuss remaining issues, which may lead to further revision of existing guidelines or development of new ones. Drug product development scientists need to collect adequate and relevant development data for a successful product registration. The key is the ability to justify the final drug product in terms of choice of the drug product formulation, container closure system, and manufacturing process. LAY ABSTRACT: The drug product development process for proteins has matured today, largely due to the rapid growth of the biotechnology industry. In this process, many regulatory guidelines/directories were developed and issued, especially through the International Conference of Harmonization (ICH). However, they were issued separately on different topics and in different time periods. An integration of all relevant guidelines into the corresponding areas in drug product development would greatly facilitate the development process. The purpose of this short review is to integrate the relevant (mainly ICH) regulatory guidelines into protein drug product development and to discuss remaining issues, which may lead to further revision of existing guidelines or development of new ones. Drug product development scientists need to collect adequate and relevant development data for a successful product registration. The key is the ability to justify the final drug product in terms of choice of the product formulation, container closure system, and manufacturing process. PMID- 26889053 TI - Impact of Vial Capping on Residual Seal Force and Container Closure Integrity. AB - The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. Additionally, container closure integrity of these samples was measured using helium leakage (physical container closure integrity) and compared to characterization data. The different capping equipment settings lead to residual seal force values from 7 to 115 N. High residual seal force values were achieved with high capping pre-compression force and a short distance between the capping plate and plunge. The choice of container closure system influenced the obtained residual seal force values. The residual seal force tester and piezoelectric measurements showed similar trends. All vials passed physical container closure integrity testing, and no stopper rupture was seen with any of the settings applied, suggesting that container closure integrity was warranted for the studied container closure system with the chosen capping setting ranges. LAY ABSTRACT: The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied. In this study we applied several methods-residual seal force tester, a self developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. The residual seal force tester can analyze a variety of different container closure systems independent of the capping equipment. An adequate and safe residual seal force range for each container closure system configuration can be established with the residual seal force tester and additional methods like computed tomography scans and leak testing. In the residual seal force range studied, the physical container closure integrity of the container closure system was warranted. PMID- 26889054 TI - Evaluation of Bacillus oleronius as a Biological Indicator for Terminal Sterilization of Large-Volume Parenterals. AB - In the production of large-volume parenterals in Japan, equipment and devices such as tanks, pipework, and filters used in production processes are exhaustively cleaned and sterilized, and the cleanliness of water for injection, drug materials, packaging materials, and manufacturing areas is well controlled. In this environment, the bioburden is relatively low, and less heat resistant compared with microorganisms frequently used as biological indicators such as Geobacillus stearothermophilus (ATCC 7953) and Bacillus subtilis 5230 (ATCC 35021). Consequently, the majority of large-volume parenteral solutions in Japan are manufactured under low-heat sterilization conditions of F0 <2 min, so that loss of clarity of solutions and formation of degradation products of constituents are minimized. Bacillus oleronius (ATCC 700005) is listed as a biological indicator in "Guidance on the Manufacture of Sterile Pharmaceutical Products Produced by Terminal Sterilization" (guidance in Japan, issued in 2012). In this study, we investigated whether B. oleronius is an appropriate biological indicator of the efficacy of low-heat, moist-heat sterilization of large-volume parenterals. Specifically, we investigated the spore-forming ability of this microorganism in various cultivation media and measured the D-values and z-values as parameters of heat resistance. The D-values and z-values changed depending on the constituents of large-volume parenteral products. Also, the spores from B. oleronius showed a moist-heat resistance that was similar to or greater than many of the spore-forming organisms isolated from Japanese parenteral manufacturing processes. Taken together, these results indicate that B. oleronius is suitable as a biological indicator for sterility assurance of large-volume parenteral solutions subjected to low-heat, moist-heat terminal sterilization. PMID- 26889057 TI - Pharmacy is Right for Me. PMID- 26889055 TI - Feasibility of Using Fluorescence Spectrophotometry to Develop a Sensitive Dye Immersion Method for Container Closure Integrity Testing of Prefilled Syringes. AB - A feasibility study was conducted for a sensitive and robust dye immersion method for the measurement of container closure integrity of unopened prefilled syringes using fluorescence spectrophotometry as the detection method. A Varian Cary Eclipse spectrofluorometer was used with a custom-made sample holder to position the intact syringe in the sample compartment for fluorescence measurements. Methylene blue solution was initially evaluated as the fluorophore in a syringe with excitation at 607 nm and emission at 682 nm, which generated a limit of detection of 0.05 MUg/mL. Further studies were conducted using rhodamine 123, a dye with stronger fluorescence. Using 480 nm excitation and 525 nm emission, the dye in the syringe could be easily detected at levels as low as 0.001 MUg/mL. The relative standard deviation for 10 measurements of a sample of 0.005 MUg/mL (with repositioning of the syringe after each measurement) was less than 1.1%. A number of operational parameters were optimized, including the photomultiplier tube voltage, excitation, and emission slit widths. The specificity of the testing was challenged by using marketed drug products and a protein sample, which showed no interference to the rhodamine detection. Results obtained from this study demonstrated that using rhodamine 123 for container closure integrity testing with in-situ (in-syringe) fluorescence measurements significantly enhanced the sensitivity and robustness of the testing and effectively overcame limitations of the traditional methylene blue method with visual or UV-visible absorption detection. LAY ABSTRACT: Ensuring container closure integrity of injectable pharmaceutical products is necessary to maintain quality throughout the shelf life of a sterile drug product. Container closure integrity testing has routinely been used to evaluate closure integrity during product development and production line qualification of prefilled syringes, vials, and devices. However, container closure integrity testing has recently gained industry attention due to increased regulatory agency scrutiny regarding the analytical rigor of container closure integrity testing methods and expectations to use container closure integrity testing in lieu of sterility tests in stability programs. Methylene blue dye is often used for dye ingress testing of container closure integrity, but we found it unsuitable for reliable detection of small breaches in prefilled syringes of drug product. This work describes the suitability and advantages of using a fluorescent dye and spectroscopic detection for a robust, sensitive, and quality control-friendly container closure integrity testing method for prefilled syringes. PMID- 26889056 TI - Particulate Study on NeoProfen, a Neonatal Injectable Product. AB - NeoProfen or sterile ibuprofen L-lysine at 10 mg/mL ibuprofen, in 2 mL single-use Type I glass vials is often a first choice medication used to close a patent ductus arteriosus in neonatal patients from 500 to 1500 g body weight. Visible particulate matter was found in vials that were placed on a commercial stability program prior to the approved expiration date of 2 years. A combination of instrumental techniques including inductively coupled plasma-mass spectrometry, x ray photoelectron spectroscopy, scanning electron microscopy energy dispersive x ray spectrometry, and Raman and Fourier transform infrared microspectroscopy was used to evaluate stability, pilot batch and packaging samples in a root cause investigation. The particulate matter was shown to consist largely of ibuprofen aluminum salts of various stoichiometries. It developed over time by a substitution mechanism, in which the ibuprofen anion in solution reacts with the aluminum oxide network of the borosilicate glass giving the ibuprofen aluminum salt with =Al-OH remaining in the network. For corrective action an alternate Type I borosilicate glass vial with interior coating, not found in the original vial, was chosen for the product to prevent this occurrence. LAY ABSTRACT: NeoProfen (sterile preservative-free ibuprofin L-lysine at 17 mg/mL in a single use glass vial) is used to close a clinically significant patent ductus arteriosus in premature infants no more than 32 weeks gestational age. The neonatal population is especially sensitive to outside chemical, physical and environmental conditions because of incompletely developed organ systems, low birth weight and other underlying conditions. Two batches of this product were voluntarily recalled by the manufacturer, Lundbeck, and investigated for the source of particulate matter observed during a commercial stability testing program. This was found to result from an interaction between the product and the Type I borosilicate glass vial where ibuprofen substitutes for the aluminum oxide network in the glass, forming an ibuprofen aluminum hydroxide salt as particulate. In order to prevent this salt formation an alternate glass vial was chosen which had interiors treated using a chemical vapor deposition technique. These vials were found to preserve NeoProfen quality properties during short term stress and medium term stability studies. PMID- 26889058 TI - The Disconnect. PMID- 26889059 TI - Do We Need More Utility Infielders? PMID- 26889060 TI - Rethinking the Role of Clinical Practice Guidelines in Pharmacy Education. AB - Clinical practice guidelines (CPGs) play a major role in pharmacy education. Students learn to locate, retrieve, and apply CPGs in didactic coursework and practice experiences. However, they often memorize and quote recommendations without critical analysis, which tends to undermine their clinical growth. Students should become genuine drug experts, based on strong critical-thinking skills and the ability to assimilate extensive clinical and scientific knowledge. Clinical practice guidelines improve health care, and students should be familiar with them, but there are legitimate criticisms of CPGs, stemming largely from potential conflicts of interest and limitations in the quality and scope of available evidence. Despite such flaws, CPGs can be used to facilitate the clinical growth of students if the emphasis is placed on critically analyzing and evaluating CPG recommendations, as opposed to blindly accepting them. From that perspective, the role that CPGs have come to play in education may need to be reconsidered. PMID- 26889061 TI - Practical Team-Based Learning from Planning to Implementation. AB - Team-based learning (TBL) helps instructors develop an active teaching approach for the classroom through group work. The TBL infrastructure engages students in the learning process through the Readiness Assessment Process, problem-solving through team discussions, and peer feedback to ensure accountability. This manuscript describes the benefits and barriers of TBL, and the tools necessary for developing, implementing, and critically evaluating the technique within coursework in a user-friendly method. Specifically, the manuscript describes the processes underpinning effective TBL development, preparation, implementation, assessment, and evaluation, as well as practical techniques and advice from authors' classroom experiences. The paper also highlights published articles in the area of TBL in education, with a focus on pharmacy education. PMID- 26889062 TI - Development and Implementation of an Advising Program's Meet-and-Greet Session. AB - OBJECTIVE: To describe the implementation and perceptions of an advising program's meet-and-greet session on student/faculty interactions. DESIGN: Student advisees and faculty advisors attended a meet-and-greet program designed to facilitate introductions. Two online surveys evaluating program perceptions were electronically distributed to participants. ASSESSMENT: Twenty-eight advisors and 226 students attended; 17 faculty members and 42% (n=95) of students completed the survey. Advisors and advisees found the program valuable (100%, 85%) and recommended holding it again (100%, 93%), respectively. Most advisors agreed that the event improved success in meeting advisees while reducing time needed to schedule and meet with advisees. Students felt more comfortable contacting advisors after participating, with 83% agreeing it was more convenient than scheduling separate meeting times. CONCLUSION: An advising meet-and-greet program facilitated initial advisee/advisor meetings while reducing self-reported faculty time/resources. This activity could be implemented by other institutions seeking to promote student advising relationships. PMID- 26889064 TI - Creating and Assessing Student Perception of an Examination Mastery Score Report for a Pharmacotherapy Course. AB - OBJECTIVE: To compare student-perceived utility of two types of score reports. METHODS: Assessment standards were followed to create a new examination score report for pharmacotherapy coursework. Student examination scores were returned using the traditional score report, the utility of which students rated along 9 dimensions. A mastery score report was also distributed, and students rated it on the same 9 dimensions. The ratings were compared to determine which the students perceived as more useful. RESULTS: The students rated the mastery score report significantly better on each of the 9 dimensions and in aggregate. CONCLUSION: Pharmacy students perceived the mastery score report as more useful in helping them improve their achievement of educational outcomes. PMID- 26889063 TI - Student-Valued Measurable Teaching Behaviors of Award-Winning Pharmacy Preceptors. AB - OBJECTIVE: To identify specific preceptor teaching-coaching, role modeling, and facilitating behaviors valued by pharmacy students and to develop measures of those behaviors that can be used for an experiential education quality assurance program. METHODS: Using a qualitative research approach, we conducted a thematic analysis of student comments about excellent preceptors to identify behaviors exhibited by those preceptors. Identified behaviors were sorted according to the preceptor's role as role model, teacher/coach, or learning facilitator; measurable descriptors for each behavior were then developed. RESULTS: Data analysis resulted in identification of 15 measurable behavior themes, the most frequent being: having an interest in student learning and success, making time for students, and displaying a positive preceptor attitude. Measureable descriptors were developed for 5 role-modeling behaviors, 6 teaching-coaching behaviors, and 4 facilitating behaviors. CONCLUSION: Preceptors may need to be evaluated in their separate roles as teacher-coach, role model, and learning facilitator. The developed measures in this report could be used in site quality evaluation. PMID- 26889065 TI - Using Bourdieu's Theoretical Framework to Examine How the Pharmacy Educator Views Pharmacy Knowledge. AB - OBJECTIVE: To explore how different pharmacy educators view pharmacy knowledge within the United Kingdom MPharm program and to relate these findings to Pierre Bourdieu's theoretical framework. METHODS: Twelve qualitative interviews were conducted with 4 faculty members from 3 different types of schools of pharmacy in the United Kingdom: a newer school, an established teaching-based school, and an established research-intensive school. Selection was based on a representation of both science-based and practice-based disciplines, gender balance, and teaching experience. RESULTS: The interview transcripts indicated how these members of the academic community describe knowledge. There was a polarization between science based and practice-based educators in terms of Bourdieu's description of field, species of capital, and habitus. CONCLUSION: A Bourdieusian perspective on the differences among faculty member responses supports our understanding of curriculum integration and offers some practical implications for the future development of pharmacy programs. PMID- 26889066 TI - Relationship of Prepharmacy Repeat Course History to Students' Early Academic Difficulty in a Pharmacy Curriculum. AB - OBJECTIVE: To examine the relationship between students' prepharmacy repeat course history and their academic difficulties early in a professional pharmacy program in conjunction with other prerequisite success variables known to predict academic difficulty. METHODS: For students admitted to a pharmacy program in 2010 and 2011 (n=160), admission variables [eg, prepharmacy coursework, grade point average (GPA)] and pharmacy program academic difficulty data (ie, academic difficulty defined as a pharmacy GPA in the bottom quartile of the class after 3 semesters of pharmacy course work) were extracted. Regression analysis was employed to examine the relationship between admission variables and academic difficulty. RESULTS: Twenty-six percent of the students (n=42) repeated a course, and 50% of these students (n=21) repeated more than one course. All of the admissions variables studied were found to individually increase the odds of a student having academic difficulty early in the pharmacy program. Specifically, repeat of a prepharmacy course increased the odds of academic difficulty threefold. CONCLUSION: Repeating prepharmacy coursework appears to be a strong indicator of future academic difficulties early in a professional pharmacy program. PMID- 26889067 TI - Interprofessional Peer Teaching of Pharmacy and Physical Therapy Students. AB - OBJECTIVE: To evaluate an interprofessional peer-teaching activity during which physical therapy students instructed undergraduate pharmacy students on 3 ambulatory devices (canes, crutches, walkers). DESIGN: The pre/post evaluation of 2 pharmacy undergraduate classes included 220 students, 110 per year. After pharmacy students completed a 10-point, knowledge-based pretest, they participated in a hands-on activity with physical therapy students teaching them about sizing, use, and safety of canes, crutches, and walkers. A 10-point posttest was completed immediately afterward. ASSESSMENT: The mean difference of pre/post scores was 3.5 (SD 1.9) for the peer-led teaching, and 3.8 (SD 2.2) for the peer learning group. Students had positive responses regarding the learning exercise and recommended further peer teaching. CONCLUSION: The peer-learning activity involving physical therapy students teaching pharmacy students was an effective method of improving knowledge and skills regarding basic ambulatory devices. PMID- 26889068 TI - Early Introduction to Professional and Ethical Dilemmas in a Pharmaceutical Care Laboratory Course. AB - OBJECTIVE: To study the effects of an early professional development series in a pharmaceutical care laboratory (PCL) course on first-year pharmacy students' perceptions of the importance of professional attitudes and action. DESIGN: Three hundred thirty-four first-year students enrolled in a PCL course participated in a new required learning activity centered on development of professional attitudes and behaviors. Students discussed situational dilemmas in pharmacy practice in small groups, highlighting application of the Oath of a Pharmacist and the Pharmacists' Code of Ethics. ASSESSMENT: Students completed an optional questionnaire at the beginning and end of the semester to assess change in their attitudes and behaviors related to professionalism in pharmacy practice. CONCLUSION: While students entered their training with a strong appreciation for professionalism, they felt more confident in applying the Oath of a Pharmacist and the Pharmacists Code of Ethics to dilemmas in practice following the new learning activity. PMID- 26889069 TI - An Elective Course on Antimicrobial Stewardship. AB - OBJECTIVE: To implement an antimicrobial stewardship (AS) elective course for second-year and third-year pharmacy students and to assess its impact on students' perceptions regarding the application of AS principles. DESIGN: A 2 credit elective course focusing on principles of AS incorporated prelecture didactic recordings with primary literature and guideline-based reading assignments, in-class active-learning group work and student-led presentations, and student-generated examination items. ASSESSMENT: Perceptions were assessed by precourse and postcourse survey items. Graded course assessments included completion of preclass assignments (readings, prerecorded lecture and writing assessment items), in-class active participation and group presentations, a midpoint examination, and a final examination. CONCLUSION: An AS-themed elective course in a doctor of pharmacy curriculum incorporating preclass, self-directed learning and in-class group-based active-learning strategies positively impacted students' perceived understanding of AS strategies. PMID- 26889071 TI - Letters. PMID- 26889070 TI - Comparison of Aseptic Compounding Errors Before and After Modified Laboratory and Introductory Pharmacy Practice Experiences. AB - OBJECTIVE: To determine whether aseptic compounding errors were reduced at the end of the third professional year after modifying pharmacy practice laboratories and implementing an institutional introductory pharmacy practice experience (IPPE). DESIGN: An aseptic compounding laboratory, previously occurring during the third-year spring semester, was added to the second-year spring semester. An 80-hour institutional IPPE was also added in the summer between the second and third years. Instructors recorded aseptic compounding errors using a grading checklist for second-year and third-year student assessments. Third-year student aseptic compounding errors were assessed prior to the curricular changes and for 2 subsequent years for students on the Oklahoma City and Tulsa campuses of the University of Oklahoma. ASSESSMENT: Both third-year cohorts committed fewer aseptic technique errors than they did during their second years, and the probability was significantly lower for students on the Oklahoma City campus. The probability of committing major aseptic technique errors was significantly lower for 2 consecutive third-year cohorts after the curricular changes. CONCLUSION: The addition of second-year aseptic compounding laboratory experiences and third year institutional IPPE content reduced instructor-assessed errors at the end of the third year. PMID- 26889072 TI - A New Practitioner's Perspective on Combining Interprofessional and Cultural Competence Instruction in Pharmacy School Curriculum. PMID- 26889078 TI - Pharmacy Practice, Education, and Research in the Era of Big Data: 2014-15 Argus Commission Report. PMID- 26889079 TI - Assessing the Impact of Drug Use and Drug Selling on Violent Offending in a Panel of Delinquent Youth. AB - Despite a vast number of empirical studies arguing for or against a causal relationship between illegal drug use and selling and violent behavior, the debate continues. In part this is due to methodological weaknesses of previous research. Using data from the Rochester Youth Development Study, the current study seeks to improve on prior research designs to allow for a more precise examination of the mechanisms that lead from an individual's drug use (chiefly, marijuana use in the current sample) and drug selling to violent action. Results will allow for greater confidence in making causal inference regarding a long standing concern in the discipline. PMID- 26889080 TI - Preparation and characterization of silymarin synchronized-release microporous osmotic pump tablets. AB - The pharmacological activity of herbal medicine is an overall action of each component in accordance with their original proportion. An efficient, sustained, and controlled-release drug delivery system of herbal medicine should ensure the synchronized drug release of each active component during the entire release procedure. In this study, silymarin (SM), a poorly soluble herbal medicine, was selected as a model drug to develop a synchronized-release drug delivery system: an SM microporous osmotic pump (MPOP) tablet. The SM was conjugated with phospholipid (SM phytosome complex, SM-PC) to improve the solubility, and the difference in the apparent octanol-water partition coefficient between the two components was significantly reduced. The dissolution rate of SM-PC was significantly higher than SM active pharmaceutical ingredients and was the same as that of the commercial SM capsule. The SM-PC was used to generate the MPOP tablet. SM was mixed with poly(ethylene) oxide and sodium chloride (an osmotic agent) to form the MPOP core, followed by coating with cellulose acetate and poly(ethylene) oxide to generate the SM MPOP. The results demonstrated that SM MPOP could synchronically and sustainably release the five active components within 12 hours (the similar coefficient f 2 between two components was >65), and the average cumulative release rate was 85%. Fitting of the drug-release curve showed a zero-order release profile for SM MPOP. Our study showed that the phytosome complex technique combined with the MPOP system will achieve synchronized release of the various active components of herbal medicine and have potential applications in developing sustained release preparations in herbal medicine. PMID- 26889083 TI - Erratum: Development of an integral assessment approach of health status in patients with obstructive airway diseases: the CORONA study [Corrigendum]. AB - [This corrects the article on p. 2413 in vol. 10, PMID: 26609228.]. PMID- 26889081 TI - Profile of tofacitinib citrate and its potential in the treatment of moderate-to severe chronic plaque psoriasis. AB - The outlook for patients with psoriasis has improved significantly over the last 10 years with the introduction of targeted therapies. Cytokines exert their effects by activating intracellular signaling and transcription pathways, among which there are Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) pathways. JAKs are intracellular second messengers that are crucial for transmitting extracellular cytokine signals to the cell. JAK inhibition interrupts intracellular signaling and can suppress immune cell activation and inflammation in T-cell-mediated disorders, such as psoriasis. Consequently, JAKs are the subject of intensive research activity, since they represent possible therapeutic targets. Tofacitinib is an orally available compound belonging to a novel category of nonbiologic drugs, the "JAK inhibitors", which target JAKs. Recently, oral and topical formulations of tofacitinib have been demonstrated to be safe and effective for the treatment of plaque psoriasis in randomized clinical trials. In particular, a 10 mg bid dose of tofacitinib was shown to be noninferior to etanercept 50 mg subcutaneously twice weekly. Questions remain unresolved regarding the safety risk beyond the 5 mg bid dose. This review, assessing the available scientific literature, focuses on the profile of tofacitinib, as investigational compound in the treatment of plaque psoriasis. An overview of the efficacy and safety data from randomized clinical trials is provided. In addition, the authors highlight future potential applications of tofacitinib in other skin diseases, in particular alopecia areata and vitiligo. PMID- 26889082 TI - Relationship of coronary collateral circulation with eosinophils in patients with unstable angina pectoris. AB - BACKGROUND: Eosinophils (EOS) have been associated with prognosis of patients with coronary artery disease, and those who showed plenitudinous coronary collateral circulation (CCC) often have good clinical consequences. However, the relationship between EOS and CCC was seldom reported. OBJECTIVE: To investigate the relationship between EOS and CCC development in patients with unstable angina pectoris (UAP). METHODS: The study population consisted of 502 consecutive patients with UAP who underwent coronary angiography and coronary stenosis >=80%. CCC was graded according to the Rentrop grading system of 0-3. Rentrop grades of 0 and 1 indicated low-grade CCC group, whereas grades 2 and 3 indicated high grade CCC group. RESULTS: The EOS was significantly higher in the high-grade CCC group compared with the low-grade CCC group. In multiple logistic regression analysis, EOS (odds ratio: 1.969; 95% confidence interval [CI]: 1.210-3.3205; P=0.006) and neutrophil count (odds ratio: 0.757; 95% CI: 0.584-0.981; P=0.035) were predictors of high-grade CCC development. EOS of >0.12*10(9)/L could independently predict high-grade CCC with 72.5% sensitivity and 58.4% specificity (area under the curve: 0.681; 95% CI: 0.632-0.729). CONCLUSION: EOS were associated with high-grade CCC in patients with UAP with coronary stenosis >=80%. Increased EOS count may play an important role in the development of CCC in patients with UAP. PMID- 26889086 TI - Abnormal expression of calcyphosine is associated with poor prognosis and cell biology function in colorectal cancer. AB - The aim of this study was to investigate the calcyphosine (CAPS) expression in human colorectal cancer (CRC) and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan-Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004), invasive depth (P<0.001), lymph node metastasis (P=0.003), tumor node metastasis stage (P=0.017), and distant metastasis (P=0.042). Furthermore, silencing of CAPS expression in CRC cells inhibited their proliferation, colony formation, migration, and invasion. Kaplan-Meier survival analysis showed that high CAPS expression might demonstrate poor prognosis in CRC patients. Cox regression analysis revealed that CAPS expression was an independent prognostic factor of CRC. Our data suggested that the upregulation of CAPS might play a role in the carcinogenesis and progression of CRC. CAPS could be used as a potential diagnostic factor and be an independent good prognostic indicator for CRC patients. PMID- 26889085 TI - Interprofessional teamwork innovations for primary health care practices and practitioners: evidence from a comparison of reform in three countries. AB - CONTEXT: A key aim of reforms to primary health care (PHC) in many countries has been to enhance interprofessional teamwork. However, the impact of these changes on practitioners has not been well understood. OBJECTIVE: To assess the impact of reform policies and interventions that have aimed to create or enhance teamwork on professional communication relationships, roles, and work satisfaction in PHC practices. DESIGN: Collaborative synthesis of 12 mixed methods studies. SETTING: Primary care practices undergoing transformational change in three countries: Australia, Canada, and the USA, including three Canadian provinces (Alberta, Ontario, and Quebec). METHODS: We conducted a synthesis and secondary analysis of 12 qualitative and quantitative studies conducted by the authors in order to understand the impacts and how they were influenced by local context. RESULTS: There was a diverse range of complex reforms seeking to foster interprofessional teamwork in the care of patients with chronic disease. The impact on communication and relationships between different professional groups, the roles of nursing and allied health services, and the expressed satisfaction of PHC providers with their work varied more within than between jurisdictions. These variations were associated with local contextual factors such as the size, power dynamics, leadership, and physical environment of the practice. Unintended consequences included deterioration of the work satisfaction of some team members and conflict between medical and nonmedical professional groups. CONCLUSION: The variation in impacts can be understood to have arisen from the complexity of interprofessional dynamics at the practice level. The same characteristic could have both positive and negative influence on different aspects (eg, larger practice may have less capacity for adoption but more capacity to support interprofessional practice). Thus, the impacts are not entirely predictable and need to be monitored, and so that interventions can be adapted at the local level. PMID- 26889084 TI - Association of nuclear and mitochondrial genes with audiological examinations in Iranian patients with nonaminoglycoside antibiotics-induced hearing loss. AB - Mitochondrial DNA mutations play an important role in causing sensorineural hearing loss. The purpose of this study was to determine the association of the mitochondrial genes RNR1, MT-TL1, and ND1 as well as the nuclear genes GJB2 and GJB6 with audiological examinations in nonfamilial Iranians with cochlear implants, using polymerase chain reaction, DNA sequencing, and RNA secondary structure analysis. We found that there were no novel mutations in the mitochondrial gene 12S rRNA (MT-RNR1) in patients with and without GJB2 mutation (GJB2(+) and GJB2(-), respectively), but a total of six polymorphisms were found. No mutations were observed in tRNA(Leu) (() (UUR) ()) (MT-TL1). Furthermore, eight polymorphisms were found in the mitochondrial ND1 gene. Additionally, no mutations were observed in the nuclear GJB6 gene in patients in the GJB2(-) and GJB2(+) groups. The speech intelligibility rating and category of auditory perception tests were statistically assessed in patients in the GJB2(-) and GJB2(+) groups. The results indicated that there was a significant difference (P<0.05) between the categories of auditory perception score in the GJB2(-) group compared to that in the GJB2(+) group. Successful cochlear implantation was observed among individuals with GJB2 mutations (GJB2(+)) and mitochondrial polymorphisms compared to those without GJB2 mutations (GJB2(-)). In conclusion, the outcome of this study suggests that variation in the mitochondrial and nuclear genes may influence the penetrance of deafness. Therefore, further genetic and functional studies are required to help patients in making the best choice for cochlear implants. PMID- 26889087 TI - PD-1/PD-L1 blockades in non-small-cell lung cancer therapy. AB - Lung cancer is the leading cause of cancer death in males and the second leading cause of death in females worldwide. Non-small-cell lung cancer (NSCLC) is the main pathological type of lung cancer, and most newly diagnosed NSCLC patients cannot undergo surgery because the disease is already locally advanced or metastatic. Despite chemoradiotherapy and targeted therapy improving clinical outcomes, overall survival remains poor. Immune checkpoint blockade, especially blockade of programmed death-1 (PD-1) receptor and its ligand PD-L1, achieved robust responses and improved survival for patients with locally advanced/metastatic NSCLC in preclinical and clinical studies. However, with regard to PD-1/PD-L1 checkpoint blockade as monotherapy or in combination with other antitumor therapies, such as chemotherapy, radiotherapy (including conventional irradiation and stereotactic body radiotherapy), and target therapy, there are still many unknowns in treating patients with NSCLC. Despite this limited understanding, checkpoint blockade as a novel therapeutic approach may change the treatment paradigm of NSCLC in the future. Here we review the main results from completed and ongoing studies to investigate the feasibility of PD 1/PD-L1 inhibitors, as monotherapy or combinatorial agents in patients with locally advanced and metastatic NSCLC, and explore optimal strategy in such patients. PMID- 26889088 TI - Long-term gene therapy with Del1 fragment using nonviral vectors in mice with explanted tumors. AB - Cancer gene therapy using nonviral vectors is useful for long periods of treatment because such vectors are both safe and inexpensive, and thus can be used repeatedly. It has been reported that gene therapy with an E3C1 fragment of Del1 in a mouse explanted tumor model improved prognosis. The present study aimed to analyze the long-term effects of repeated non-viral gene transfer of E3C1. Mice with explanted tumors of SCCKN cells, a human squamous carcinoma, were treated with a plasmid encoding E3C1. Plasmids were injected locally every week using a transfection reagent. Control mice treated with mock DNA started to be euthanized on day 18, because the tumors had grown to over 15% of the body weight, and all of them had died by day 43. On the other hand, the tumors in two of ten mice treated with E3C1 had disappeared. The other eight mice started to be euthanized on day 46 and eight of ten mice had been euthanized by day 197. After 18 days of therapy, the tumor volume of control mice was 2,804+/-829 mm(3) and that of the E3C1 mice was 197+/-159 mm(3). Histochemical studies showed enhanced apoptosis in the E3C1-treated tumors, as compared with controls. Changes in cell morphology and decreased polymerized actin induced by E3C1 indicated disturbed cell adhesion to the matrix. In in vitro studies of SCCKN cells, prolonged administration of an E3C1 recombinant protein to cultured cells reduced adhesion independent growth of cancer cells, as compared with control cells. These data suggest that E3C1 treatment induces anoikis. PMID- 26889089 TI - Tumor heterogeneity as a rationale for a multi-epitope approach in an autologous renal cell cancer tumor vaccine. AB - PURPOSE: An autologous tumor vaccine already used successfully in the immune therapy of renal cell carcinoma was investigated in detail. The evaluation of potential tumor markers should allow for the assessment of potency according to pharmaceutical regulations. METHODS: A panel of 36 tumor-associated antigens and cellular marker proteins was characterized in a total of 133 tumor cell lysates by methods such as ELISA, Western blots, and topological proteomics. The induction of tumor-associated antigen-specific antibodies was demonstrated by immunization in mice. RESULTS: Tumor heterogeneity was demonstrated: none of the tumor-associated antigens investigated were detectable in each tumor lysate. In parallel, the coincidental presence of potential danger signals was shown for HSP 60 and HSP-70. The presence of both antigen and danger signal allowed a successful induction of an immune response in a murine model. CONCLUSION: The verified tumor heterogeneity indicates the need for a multi-epitope approach for the successful immunotherapy in renal cell carcinoma. PMID- 26889091 TI - Challenging hepatitis C-infected liver transplant patients. AB - Caring for liver transplant patients suffering from chronic hepatitis C virus (HCV) infection is a challenging task for transplant surgeons and primary physicians alike. HCV is the leading cause of liver transplantation in the USA and comes with a myriad of complications that increase morbidity and mortality. This review focuses on patient follow-up, spanning from before the liver transplant occurs to the patient's long-term health. Pretransplant, both donor and recipient variables, must be carefully chosen to ensure optimal surgical success. Risk factors must be identified and HCV viral load must be reduced to a minimum. In addition to standard transplant complications, HCV patients suffer from additional problems, such as fibrosing cholestatic hepatitis and widespread viremia. Physicians must focus on the balance of immunosuppressive and antiviral medications, while considering possible side effects from these potent drugs. Over the years following surgery, physicians must identify any signs of failing liver health, as HCV-positive patients have an increased risk for cirrhosis and certain life-threatening malignancies. PMID- 26889092 TI - Solamargine triggers cellular necrosis selectively in different types of human melanoma cancer cells through extrinsic lysosomal mitochondrial death pathway. AB - BACKGROUND: Previous reports showed that the Steroidal Glycoalkaloid Solamargine inhibited proliferation of non-melanoma skin cancer cells. However, Solamargine was not tested systematically on different types of melanoma cells and was not simultaneously tested on normal cells either. In this study we aimed to investigate the effect of Solamargine and the mechanism involved in inhibiting the growth of different types of melanoma cells. METHODS: Solamargine effect was tested on normal cells and on another three melanoma cell lines. Vertical growth phase metastatic and primary melanoma cell lines WM239 and WM115, respectively and the radial growth phase benign melanoma cells WM35 were used. The half inhibitory concentration IC50 of Solamargine was determined using Alamarblue assay. The cellular and subcellular changes were assessed using light and Transmission Electron Microscope, respectively. The percentage of cells undergoing apoptosis and necrosis were measured using Flow cytometry. The different protein expression was detected and measured using western blotting. The efficacy of Solamargine was determined by performing the clonogenic assay. The data collected was analyzed statistically on the means of the triplicate of at least three independent repeated experiments using one-way ANOVA test for parametric data and Kruskal-Wallis for non-parametric data. Differences were considered significant when the P values were less than 0.05. RESULTS: Hereby, we demonstrate that Solamargine rapidly, selectively and effectively inhibited the growth of metastatic and primary melanoma cells WM239 and WM115 respectively, with minimum effect on normal and benign WM35 cells. Solamargine caused cellular necrosis to the two malignant melanoma cell lines (WM115, WM239), by rapid induction of lysosomal membrane permeabilization as confirmed by cathepsin B upregulation which triggered the extrinsic mitochondrial death pathway represented by the release of cytochrome c and upregulation of TNFR1. Solamargine disrupted the intrinsic apoptosis pathway as revealed by the down regulation of hILP/XIAP, resulting in caspase-3 cleavage, upregulation of Bcl-xL, and Bcl2, and down regulation of Apaf-1 and Bax in WM115 and WM239 cells only. Solamargine showed high efficacy in vitro particularly against the vertical growth phase melanoma cells. CONCLUSION: Our findings suggest that Solamargine is a promising anti-malignant melanoma drug which warrants further attention. PMID- 26889090 TI - Wheat allergy: diagnosis and management. AB - Triticum aestivum (bread wheat) is the most widely grown crop worldwide. In genetically predisposed individuals, wheat can cause specific immune responses. A food allergy to wheat is characterized by T helper type 2 activation which can result in immunoglobulin E (IgE) and non-IgE mediated reactions. IgE mediated reactions are immediate, are characterized by the presence of wheat-specific IgE antibodies, and can be life-threatening. Non-IgE mediated reactions are characterized by chronic eosinophilic and lymphocytic infiltration of the gastrointestinal tract. IgE mediated responses to wheat can be related to wheat ingestion (food allergy) or wheat inhalation (respiratory allergy). A food allergy to wheat is more common in children and can be associated with a severe reaction such as anaphylaxis and wheat-dependent, exercise-induced anaphylaxis. An inhalation induced IgE mediated wheat allergy can cause baker's asthma or rhinitis, which are common occupational diseases in workers who have significant repetitive exposure to wheat flour, such as bakers. Non-IgE mediated food allergy reactions to wheat are mainly eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG), which are both characterized by chronic eosinophilic inflammation. EG is a systemic disease, and is associated with severe inflammation that requires oral steroids to resolve. EoE is a less severe disease, which can lead to complications in feeding intolerance and fibrosis. In both EoE and EG, wheat allergy diagnosis is based on both an elimination diet preceded by a tissue biopsy obtained by esophagogastroduodenoscopy in order to show the effectiveness of the diet. Diagnosis of IgE mediated wheat allergy is based on the medical history, the detection of specific IgE to wheat, and oral food challenges. Currently, the main treatment of a wheat allergy is based on avoidance of wheat altogether. However, in the near future immunotherapy may represent a valid way to treat IgE mediated reactions to wheat. PMID- 26889093 TI - KNOWLEDGE AND ATTITUDES REGARDING CHILD ABUSE AND NEGLECT. AB - PURPOSE: The aim of this study was to assess knowledge and attitude of dentists in Bosnia and Herzegovina (BH) regarding signs and symptoms of child abuse and neglect (CAN), reporting procedure and level of education. METHODS: Data were collected through a self-administrated structured questionnaire adopted and modified from previous studies. It was administrated to 300 dentists out of which a total number of 210 subjects were in final sample for statistical analyses. Response rate was seventy percent. Descriptive statistics, Chi-square and Kruskal Wallis H test were used to analyze statistical differences in responses. The level of significance was set at p<0.05. RESULTS: Dentists in BH are very rarely provided (80%) with training related to recognition and reporting of CAN. Sixty six percent of dentists had never suspected CAN in their practice. Only nine percent of dentists would report suspicious of CAN. Prevailing reasons for not reporting suspected case of CAN was lack of knowledge of the reporting procedure (43%), and combination of indicated answers that never had a case and lack of knowledge about the procedure (31%). CONCLUSION: Results of this study suggest that dentists need an effective education to increase their knowledge and awareness of all aspects of CAN. PMID- 26889095 TI - OUTCOME OF PHYSICAL THERAPY AND SPLINTING IN HAND BURNS INJURY. OUR LAST FOUR YEARS' EXPERIENCE. AB - OBJECTIVE: Burn injuries in hands are much more complex and the appearance of contractures is a common complication. Hand burn injuries often result in limited functionality, flexion and extension of fingers and present a major hindrance in rehabilitation. The aim of physical therapy and splinting after hand burn injury is to maintain mobility, prevent the development of the contracture and to promote the functionality of hand and good cosmetic results. The purpose of this study is to presents our experience of 38 children with hand burn injuries, admitted and treated at the Department of Plastic Surgery, UCCK-Pristina, Kosovo, during the years 2012-2015. METHODS: Physical therapy is focused on active/passive range of motion in affected joints, management of cicatrix, strengthening exercise, coordination and use of splints for correction contractures. Patients were evaluated in three, six months and the definitive evaluation is done after 9 months of physical therapy and splinting. RESULTS: We have improvement in range of motion (ROM), functionality, coordination, muscle force, decrease of keloids scars. CONCLUSION: This study shows the importance of physical therapy and splinting, achieving good results in preventing contracture, improving range of motion, muscle force and good cosmetic results. PMID- 26889094 TI - INCIDENCE OF ACUTE PANCREATITIS IN ALBANIAN POPULATION. AB - BACKGROUND: Acute Pancreatitis (AP) is an inflammatory pathology with large regional variations in incidence and etiology. AIM: The aim of the study was to provide a description of the epidemiologic situation of AP in Albanian population, regarding incidence, etiology and severity of the disease. METHODS: We have studied all the files of all patients with acute pancreatitis admitted at the UHC 'Mother Theresa" during an eight year period (2005-2012). THE RESULTS: We had 964 admissions with the diagnosis acute pancreatitis, making an incidence of 5.64 per 100 000 inhabitants per year. Mean age of patients was 54.5 +/- 16.93 years old. Among risk factors, alcohol consumption was found in 382 patients (39.6%), gallstone in 362 patients (37.6%), and others in 220 patients (22.8%). CONCLUSION: The incidence of acute pancreatitis in Albania ranges from 3.6 - 5.64 new cases per 100 000 inhabitants per year, with an increasing trend during the last years. The incidence of AP among females almost doubles during 2005-2012. Alcohol consumption is the predominating etiologic factor among young males. PMID- 26889096 TI - BIOPSYCHOSOCIAL DETERMINANTS OF HYPOACTIVE SEXUAL DESIRE IN WOMEN: A NARRATIVE REVIEW. AB - BACKGROUND: As a mental response to sexual stimuli, sexual desire determines human sexual behavior and represents the cognitive capacity of sexual stimulation, so that avoiding sexual activity has a very negative effect on the discharge of intimacy and joy in couple's relationship and threatens the stability relationship, which can finally end in sexual dissatisfaction and divorce; it may even affect the reproduction. This study, reviews the literature on biopsychosocial determinants of hypoactive sexual desire disorder in women in childbearing ages. METHOD: The search was done from January to March 2015 by the use of the data bases ProQuest, Pubmed, CINAHL, Ovid and Medline and the words sexual desire, related factors and biopsychosocial determinants were used as free text words. The words reduce sexual desire, hypoactive sexual desire disorder, dyadic relationship, biopsychosocial factors and women were used as keywords in the search. Also, the articles focusing on any aspects of sexual desire such as biological, social and psychological factors and relationship factors alone or integrated, were included in the study. The articles which specifically targeted the hypoactive sexual desire disorder in pregnant and lactating women and also the articles targeting biopsychosocial factors related to other types of sexual function disorder such as arousal disorder, orgasm disorder and dyspareunia, were all excluded from this study. FINDINGS: After reviewing the literature, the findings were categorized in three main class of effect of biologic factors on sexual desire and sexual hypoactivity, the effect of psychological factors on sexual desire and the effect of cultural factors and couple's relationship on sexual desire, each of these domains cover a wide range (such as hormonal changes, chronic diseases, psychological difficulties (perceived stress, anxiety, depression). Incompatibility of couples, the spouse's sexual function disorder) which may overlap. Because of the complexity of etiology and the difficulty of treating hypoactive sexual desire disorder, it is necessary to use biopsychosocial approaches to diagnose and treat the disorder. CONCLUSION: According to the findings of this reviewing study, the factors able to affect sexual desire and activity are not distinct and often overlap, therefore, the complicated etiology of hypoactive sexual desire disorder often needs multidimensional intervention to use biopsychosocial approach; Multi factor assessment with a combination of psychological, physical, social and hormonal intervention can be effective in making strategies to treat the symptoms of HSDD. PMID- 26889098 TI - IMPACT OF FLUORIDE ON DENTAL HEALTH QUALITY. AB - INTRODUCTION: Fluoride is natural element that strengthens teeth and prevents their decay. Experts believe that the best way to prevent cavities is the use of fluoride from multiple sources. Studies even show that in some cases, fluoride can stop already started damage of the teeth. In children younger than 6 years fluoride is incorporated into the enamel of permanent teeth, making the teeth more resistant to the action of bacterial and acids in food. GOAL: The aim of this study is to determine the effects of improving the health status of teeth after six months treatment with the use of topical fluoridation 0.5% NaF, and the level and quality of the impact of treatment with chemical 0.5% NaF on the dental health of children at age from 8 to 15 years, in relation to gender and chronological age. This study included school children aged 8 to 15 years who visited health and dental services dependent in Mostar. RESULTS: It is obvious that after the implementation of treatment with 5% NaF by the method of topical fluoridation, health status of subjects from the experimental group significantly improved, so that at the final review 89.71% or 61 subjects of the experimental group had healthy (cured teeth), tooth with dental caries only 5.88% or 4 respondents tooth with dental caries and filling 4.41% or 3 respondents, extracted baby tooth 14.71% or 10 respondents, while for 13.24% of respondents was identified state with still unerupted teeth. Our findings are indirectly confirmed that the six-month treatment of fluoridation with 5% NaF, contributed to statistically significant improvement in overall oral health of the experimental group compared to the control group which was not treated by any dental treatment. CONCLUSION: It can be concluded that there is a statistically significant difference in the evaluated parameters of oral health of children in the control group compared to the studied parameters of oral health the experimental group of children at the final dental examination. PMID- 26889097 TI - RESOURCE MANAGEMENT AMONG INTENSIVE CARE NURSES: AN ETHNOGRAPHIC STUDY. AB - BACKGROUND: Nurses are the main users of supplies and equipment applied in the Intensive Care Units (ICUs) which are high-priced and costly. Therefore, understanding ICU nurses' experiences about resource management contributes to the better control of the costs. OBJECTIVES: This study aimed to investigate the culture of nurses' working environment regarding the resource management in the ICUs in Iran. PATIENTS AND METHODS: In this study, a focused ethnographic method was used. Twenty-eight informants among ICU nurses and other professional individuals were purposively selected and interviewed. As well, 400 hours of ethnographic observations as a participant observer was used for data gathering. Data analysis was performed using the methods described by Miles and Huberman (1994). RESULTS: Two main themes describing the culture of ICU nurses regarding resource management included (a) consumption monitoring and auditing, and (b) prudent use. The results revealed that the efforts for resource management are conducted in the conditions of scarcity and uncertainty in supply. ICU nurses had a sense of futurism in the supply and use of resources in the unit and do the planning through taking the rules and guidelines as well as the available resources and their values into account. Improper storage of some supplies and equipment was a reaction to this uncertain condition among nurses. CONCLUSIONS: To manage the resources effectively, improvement of supply chain management in hospital seems essential. It is also necessary to hold educational classes in order to enhance the nurses' awareness on effective supply chain and storage of the items in the unit stock. PMID- 26889099 TI - BURNOUT SYNDROME AMONG EDUCATORS IN PRE-SCHOOL INSTITUTIONS. AB - INTRODUCTION: The occurrence of burnout syndrome (BS) has been recognized in many professions (pilots, firefighters, police officers, doctors...) that during their work are subjected to high levels of stress. For educators in preschool institutions stress level is very high thus creating the possibility of developing BS. MATERIAL AND METHODS: For this research is selected preschool institution - kindergarten "Radost" (Joy) in Split, in which by use of questionnaires (modified scale by Freudenberger and modified scales by Girdin, Everly and Dusek) during 2014 among educators (100 respondents) is conducted a survey regarding the frequency of burnout syndrome. RESEARCH RESULTS: According to questionnaires by Girdin, Everly and Dusek there is no statistically significant difference between the number of educators who feel good and those that are under significant stress (chi2=1.04; p=0.307). According to questionnaire by Freudenberg educators are classified into 3 categories and distribution of educators by the groups is almost uniform (chi2=2.76; p=0.250), which means that one third of a teacher is in good condition, a third is in the risk area for burn-out syndrome, while one third are candidates for development of this syndrome. Comparing a teacher in good condition compared to other (at risk and those who are candidates for the burn-out syndrome) is up to 1.5 times higher in those who are at risk and the candidates for development of this syndrome than in others (chi2=4.5; p=0.033). CONCLUSION: The occurrence of burnout syndrome is very high for the group of educators (half of the educators!) in pre-school institutions which should be taken into account by the institutions management. For this purpose, it is necessary to organize regular medical check ups with particular reference to burnout syndrome with signs of the syndrome to prevent its further development. PMID- 26889100 TI - COMPARATIVE OF DISTRACTION FACTORS AMONG MALE AND FEMALE STUDENTS OF SARI ALLIED MEDICAL SCIENCES' STUDENTS. AB - BACKGROUND: Distraction is nothing but internal intension of the mind towards involvement of the person. This research studied classroom distractions factors among students of Faculty of Allied medical Sciences in year 2014-2015, so that with the findings of the research about classroom distractors' factors and to present proposed suggestions for decreasing and removing of distractions. METHODS: This is an exploratory study. Data collection in this study was the researcher made questionnaire based on Likert-type scales. SPSS software was used for analyzing the data statistics such as mean, standard deviation and frequency ratings, each subset of the elements associated with distraction Friedman test has been used to determine the ranking of each of the components. RESULTS: 139 people participated in the six majors in this study which 91 people (65.5%) was female, and 48 people (34.5%) was male. Maximum number of 31 people (22.3) was in laboratory science, Lowest number of 15 (10.08 percent) in medical records, 25 (18%) people in Radiology, health information technology and medical emergencies which each of above course studies with 23 people (16.5 %), Anesthesiology 22 (15.8 percent) participated in this study. Among the internal factors of distraction between male and female students, the sleeping factor was in first priority and "My phone / pager ringing or answering the mobile" was in last priority. Among distraction external factors in male students, the factor "Adornment of professors" with mean 3.27 and SD=1.30 and Mean Rank=23.06 was in first priority, and among external distraction factors in girl students, the factor, "Used clothing and exotic costumes of Classmates" with mean=3.21, SD=1.30 and mean rank=22.66 was in first priority and factor of "Surroundings Noise (mowing, drilling, construction, and ...)" for male and female students was in last priority. CONCLUSIONS: Attention and concentration are crucial to effective accomplishment. If a teacher is not proficient in controlling attention, focusing and refocusing when things go awry, this can cause loss of focus and in turn create a variety of problems. PMID- 26889101 TI - THE RELATIONSHIP BETWEEN EMOTIONAL INTELLIGENCE WITH RELIGIOUS COPING AND GENERAL HEALTH OF STUDENTS. AB - AIM: This research organized to determine the relationship between Emotional Intelligence (EI) with Religious Coping and Mental Health of students at Mazandaran University of Medical Sciences. METHOD: This descriptive and analytical study was conducted in 2014 on 335 students at Mazandaran University of Medical Sciences. Students were selected by stratified random sampling method. The instruments to gather data were Bradberry and Greaves Standard Emotional Intelligence Questionnaire, the 12-item General Health Questionnaire, and the Pargament's Religious Coping. Data was analyzed by SPSS 21 via descriptive and inferential statistics (Pearson and Spearman's correlation). RESULTS: Among 335 students under investigation, 144 students were male (43%) and 191 ones were female (57%). Their ages were ranging from 17 to 34 years old (21.02+/-2.014). Average EI scores, positive religious coping, negative religious coping, and mental health were 91.27, 14.91, 4.86, 5.34, respectively. Moreover, there was a direct and significant relationship between EI and positive religious coping (r=0.282, P<0.001). CONCLUSIONS: According to the results of this study, there is a direct correlation between positive religious coping and emotional intelligence. So Strengthening religious coping can promote emotional intelligence that is one component of mental health. PMID- 26889102 TI - THE DIFFERENCE BETWEEN MU SUPPRESSION AND NURSES' EMPATHY WITH THE DIFFERENCE OF THREE YEARS OF WORK EXPERIENCE. AB - BACKGROUND: Nurse's empathy is one of the major parameters to improve the quality of provided health care known for the patient and it has a significant effect on reducing physical and psychological symptoms in patients. However, it has shown that over time and by increasing the background of nurses, their empathy is reducing. However, there is no research to investigate the Mu Suppression that is an indicator of the performance of mirror neurons that is a basis of empathy sense in the brain. So, the aim of this study is to investigate the difference between reported empathy and Mu suppression among nurses with three years of work background. METHODS: So, a total of 39 male nurse were chosen by available sampling that 15 of them has about 3 years working experience more than other's 15 people, Data collection tool was empathy questionnaire of Jefferson's health professionals. Mirror neurons' activation was investigated by Mu suppression. So, EEG was recorded in three situations including: 1) watching a video of a motionless hand, 2) watching a video of a hand that is opening and closing and 3) moving their own hand. RESULTS: The results of MANOVA analysis indicated that although Mu suppression among nurses with more background is less, but this difference is not significant. Also, there is no significant difference between the reported empathy scores by nurses among two groups. CONCLUSIONS: These results indicate that three years of work experience don't have an effect on empathy reduction. PMID- 26889103 TI - THE DETERMINANTS OF NURSING, ALLIED HEALTH AND NON MEDICAL STAFFS' HEALTH LITERACY IN HOSPITALS OF A DEVELOPING COUNTRY. AB - INTRODUCTION: Given the role of personnel working in hospitals in promoting health, there is a clear need for a study to clarify the level of health literacy and affecting factors on it among the non medical and medical staffs working in hospitals. METHODS: A cross-sectional survey was performed on 389 employees who were working in hospitals affiliated to Semnan University of Medical Sciences of Iran in 2013. RESULTS: There were significant relationships among the use of TV (P=0.044, CI=95%, Odd's Ratio= 1.825), the use of books and journals (P<0.0001, CI=95%, Odd's Ratio= 5.551), the use of internet (P<0.039, CI=95%, Odd's Ratio= 0.641), the use of physicians (P<0.0001, CI=95%, Odd's Ratio=0.070) and the nonmedical and medical staffs' health literacy level. CONCLUSIONS: The findings indicate media and print information resources more than physicians and electronic information sources affect on the increase of nonmedical and medical staffs' health literacy of hospitals of Iran. It also is better to train Iranian physicians more about the skills required for transferring health concepts. Given the important role of medical staffs in the increase of health literacy level in other members of the community, it is better to use other suitable information sources to transfer health information to all individuals in the community. PMID- 26889104 TI - INFLUENCE OF OVERWEIGHT AND OBESITY IN CHILDREN ON ANESTHESIOLOGICAL COMPLICATIONS APPEARANCE DURING ADENOIDECTOMY AND ADENOTONSILLECTOMY. AB - INTRODUCTION: Obesity in children is becoming from year to year enormous medical and socio-epidemilogical problem according to increasing number of overweight and obese children. Overweight and obesity in children mostly affects on cardiovascular, respiratory and endocrine system disturbances. Adenoidectomy and adenotonsillectomy belong to group of most often done operation in children population. Anesthesiology complications during adenodecotomy and adenotonsillectomy in children are known as very disturbing and dramatic. METHODS: Retrospective-prospective study includes 162 children, both genders, 3 to 12 years old, who are hospitalized and operated (adenoidectomies and adenotonsillectomies) on Otorihinolaryngolic clinic of University clinical centre Tuzla in the four year period. Purpose of the study is to show the influence of overweight in children on appearance of anesthesiology complications such as difficult intubation, bronchospasm and laryngospasm. Body mass index (BMI), which is used as universal measure, is adapted with gender specific scales of National statistic centre of United States of America. All children with BMI over 25 are referred as overweight and those over 30 as obese. These children categories were compared to those with normal BMI according to anesthesiology complications incidence. RESULTS: Overweight in operated children is noticed in 21%, and 11% of children was obese and there wasn't distinction between boys and girls. Anesthesiology complications are evaluated in 12 of them (7.4%). Total analyzed sample show significant connection and influence of overweight with appearance of anesthesiology complications. Separate comparison for two types of operations is indicating that during adenoidectomies there hasn't been noticed connection between overweight and anestehesiological complications, while in case of adenotonsillectomies direct and significant correlation is proven. CONCLUSIONS: According to increased risk of anesthesiology complications in overweight and obese children during adenodectomies and adenotonsillectomies it is important for anesthesiologists to do much serious preoperative evaluation of obese children, and to be more prepared for every of possible unwished supersize during perioperative period. PMID- 26889105 TI - TEAM ATTITUDE EVALUATION: AN EVALUATION IN HOSPITAL COMMITTEES. AB - INTRODUCTION: Patients' health and safety is not only a function of complex treatments and advanced therapeutic technologies but also a function of a degree based on which health care professionals fulfill their duties effectively as a team. The aim of this study was to determine the attitude of hospital committee members about teamwork in Kerman hospitals. METHODOLOGY: This study was conducted in 2014 on 171 members of clinical teams and committees of four educational hospitals in Kerman University of Medical Sciences. To collect data, the standard "team attitude evaluation" questionnaire was used. This questionnaire consisted of five domains which evaluated the team attitude in areas related to the team structure, leadership, situation monitoring, mutual support, and communication in the form of a 5-point Likert type scale. To analyze data, descriptive statistical tests, T-test, ANOVA, and linear regression were used. RESULTS: The average score of team attitude for hospital committee members was 3.9 out of 5. The findings showed that leadership had the highest score among the subscales of team work attitude, while mutual support had the lowest score. We could also observe that responsibility was an important factor in participants' team work attitude (beta = -0.184, p = 0.024). Comparing data in different subgroups revealed that employment, marital status, and responsibility were the variables affecting the participants' attitudes in the team structure domain. Marital status played a role in leadership; responsibility had a role in situation monitoring; and work experience played a role in domains of communication and mutual support. CONCLUSIONS: Hospital committee members had a positive attitude towards teamwork. Training hospital staff and paying particular attention to key elements of effectiveness in a health care team can have a pivotal role in promoting the team culture. PMID- 26889106 TI - CHALLENGES AND SUCCESSES OF HARM REDUCTION SERVICES IN WOMEN'S DROP-IN CENTRES: PERSPECTIVE OF VULNERABLE WOMEN. AB - BACKGROUND: The objective of this study was to shed light on the challenges and successes of HIV/AIDS services delivery as perceived by Sex workers. METHODS: Face-to-face semi-structured interviews were conducted with 20 IDUs and Sex workers in drop-in centers in Shiraz. A thematic analysis of these qualitative data was conducted by the authors. RESULTS: Participants identified major challenges and successes of HIV/AIDS services delivery. Access services, services delivery in terms of challenges and the successes concept were classified. CONCLUSIONS: Our study demonstrates that while there is greater availability of HIV/AIDS services, this does not equate with greater accessibility because multiple, complex and interrelated barriers to HIV/AIDS service utilization at the service delivery level such as Stigma, discrimination, violence, harassment and social equity issues are critical concerns of FSW. PMID- 26889107 TI - THE IMPORTANCE OF PLAY DURING HOSPITALIZATION OF CHILDREN. AB - INTRODUCTION: Play constitutes an essential parameter of the normal psychosomatic development of children, as well as their statutory right. It is also an important means of communication in childhood. OBJECTIVE: To review, detect and highlight all data cited regarding the role of play during the hospitalization of children. METHODOLOGY: Literature review was achieved by searching the databases Scopus, PubMed, Cinhal in English, using the following key words: therapeutic play, play therapy, hospitalized child, therapist. RESULTS: During hospitalization, play either in the form of therapeutic play, or as in the form of play therapy, is proven to be of high therapeutic value for ill children, thus contributing to both their physical and emotional well-being and to their recovery. It helps to investigate issues related to the child's experiences in the hospital and reduce the intensity of negative feelings accompanying a child's admission to hospital and hospitalization. Play is widely used in pre-operative preparation and invasive procedures, while its use among children hospitalized for cancer is beneficial. CONCLUSION: The use of play in hospital may become a tool in the hands of healthcare professionals, in order to provide substantial assistance to hospitalized children, as long as they have appropriate training, patience, and will to apply it during hospitalization. PMID- 26889108 TI - INTRAVENOUS MEDICATION ADMINISTRATION ERRORS AND THEIR CAUSES IN CARDIAC CRITICAL CARE UNITS IN IRAN. AB - BACKGROUND AND OBJECTIVES: The dangerous events caused by medication errors are one of the main challenges faced in critical care units. The present study was conducted to determine the frequency of intravenous medication administration errors and their causes in cardiac critical care units in Iran. MATERIALS AND METHODS: The present descriptive study was conducted in the critical care units (CCUs and cardiac surgery intensive care units) of 12 teaching hospitals. Of the total of 240 nurses working in these departments, 190 participated in the present study. The data collection tools used in this study included the "nurses' demographic data questionnaire", the "patients' medical and demographic data questionnaire" and the "nurses' self-reporting questionnaire about the frequency of intravenous medication administration errors and their causes". The data obtained were analyzed in SPSS-20 using descriptive statistics such as the absolute and relative frequency. FINDINGS: During the 2 months in which this study was being conducted, 2542 patients were admitted to these departments and 20240 doses of intravenous medications were administered to these patients. The nurses reported 262 intravenous medication administration errors. The most common intravenous medication error pertained to administering the wrong medication (n=71 and 27.1%). As for the causes of intravenous medication administration errors, 51.5% of the errors were associated with work conditions, 24% with packaging, 13.4% with communication, 9.9% with transcription and 1.2% with pharmacies. DISCUSSION AND CONCLUSION: According to the results, strategies are recommended to be adopted for reducing or limiting medication errors, such as building a stronger pharmacology knowledge base in nurses and nursing students, improving work conditions and improving communication between the nurses and physicians. PMID- 26889109 TI - Effects of Interrupted Wetness Periods on Conidial Germination, Germ Tube Elongation and Infection Periods of Botryosphaeria dothidea Causing Apple White Rot. AB - Responses of Botryosphaeria dothidea to interrupted wetness periods were investigated under in vivo and in vitro conditions. Conidia of B. dothidea were allowed to germinate on apple fruits under wetting condition at 25oC for 5 hr. They were air-dried for 0, 1, 2 or 4 hr, and then rewetted at 25oC for 5 hr. Following an initial wetness period of 5 hr, 83% of the conidia germinated. The percent conidial germination increased to 96% when wetting was extended continuously another 5 hr. However, no further conidial germination was observed when wetting was interrupted by dry periods of 1, 2 and 4 hr, resulting in 83, 81 and 82%, respectively. The mean length of the germ tubes was 37 MUm after 5 hr of wetting and elongated to 157 MUm after 10 hr of continuous wetting. On the other hand, interruption of wetting by a dry period of 1 hr or longer after the 5 hr of initial wetting arrested the germ tube elongation at approximately 42 MUm long. Prolonged rewetting up to 40 hr did not restore germ tube elongation on slide glasses under substrate treatments. Model simulation using weather data sets revealed that ending infection periods by a dry period of at least 1 hr decreased the daily infection periods, avoiding the overestimation of infection warning. This information can be incorpo- rated into infection models for scheduling fungicide sprays to control apple white rot with fewer fungicide applications. PMID- 26889110 TI - Lysimachia foenum-graecum Herba Extract, a Novel Biopesticide, Inhibits ABC Transporter Genes and Mycelial Growth of Magnaporthe oryzae. AB - To identify a novel biopesticide controlling rice blast disease caused by Magnaporthe oryzae, 700 plant extracts were evaluated for their inhibitory effects on mycelial growth of M. oryzae. The L. foenum-graecum Herba extract showed the lowest inhibition concentration (IC50) of 39.28 MUg/ml, which is lower than the IC50 of blasticidin S (63.06 MUg/ml), a conventional fungicide for rice blast disease. When treatments were combined, the IC50 of blasticidin S was dramatically reduced to 10.67 MUg/ml. Since ABC transporter genes are involved in fungicide resistance of many organisms, we performed RT-PCR to investigate the transcriptional changes of 40 ABC transporter family genes of M. oryzae treated with the plant extract, blasticidin S, and tetrandrine, a recognized ABC transporter inhibitor. Four ABC transporter genes were prominently activated by blasticidin S treatment, but were suppressed by combinational treatment of blasticidin S with the plant extract, or with tetrandrine that didn't show cellular toxicity by itself in this study. Mycelial death was detected via confocal microscopy at 24 h after plant extract treatment. Finally, subsequent rice field study revealed that the plant extract had high control efficacy of 63.3% and should be considered a biopesticide for rice blast disease. These results showed that extract of L. foenum graecum Herba suppresses M. oryzae ABC transporter genes inducing mycelial death and therefore may be a potent novel biopesticide. PMID- 26889111 TI - Antifungal Effect of Plant Essential Oils on Controlling Phytophthora Species. AB - In this study, antifungal activity of essential oils of Cymbopogon citratus and Ocimum basilicum and two fungicides Mancozeb and Metalaxyl-Mancozeb in six different concentrations were investigated for controlling three species of Phytophthora, including P. capsici, P. drechsleri and P. melonis on pepper, cucumber and melon under in vitro and greenhouse conditions, respectively. Under the in vitro condition, the median effective concen- tration (EC50) values (ppm) of plant essential oils and fungicides were measured. In greenhouse, soil infested with Phytophthora species was treated by adding 50 ml of essential oils and fungicides (100 ppm). Disease severity was determined after 28 days. Among two tested plant essential oils, C. citratus had the lowest EC50 values for inhibition of the mycelial growth of P. capsici (31.473), P. melonis (33.097) and P. drechsleri (69.112), respectively. The mean EC50 values for Metalaxyl-Mancozeb on these pathogens were 20.87, 20.06 and 17.70, respectively. Chemical analysis of plant essential oils by GC-MS showed that, among 42 compounds identified from C. citratus, two compounds beta-geranial (alpha-citral) (39.16%) and z-citral (30.95%) were the most abundant. Under the greenhouse condition, Metalaxyl Mancozeb caused the greatest reduction in disease severity, 84.2%, 86.8% and 92.1% on melon, cucumber, and pepper, respectively. The C. citratus essential oil reduced disease severity from 47.4% to 60.5% compared to the untreated control (p<=0.05). Essential oils of O. basilicum had the lowest effects on the pathogens under in vitro and greenhouse conditions. These results show that essential oils may contribute to the development of new antifungal agents to protect the crops from Phytophthora diseases. PMID- 26889112 TI - Proteome Analysis of Disease Resistance against Ralstonia solanacearum in Potato Cultivar CT206-10. AB - Potato is one of the most important crops worldwide. Its commercial cultivars are highly susceptible to many fungal and bacterial diseases. Among these, bacterial wilt caused by Ralstonia solanacearum causes significant yield loss. In the present study, integrated proteomics and genomics approaches were used in order to identify bacterial wilt resistant genes from Rs resistance potato cultivar CT 206-10. 2-DE and MALDI-TOF/TOF-MS analysis identified eight differentially abundant proteins including glycine-rich RNA binding protein (GRP), tomato stress induced-1 (TSI-1) protein, pathogenesis-related (STH-2) protein and pentatricopeptide repeat containing (PPR) protein in response to Rs infection. Further, semi-quantitative RT-PCR identified up-regulation in transcript levels of all these genes upon Rs infection. Taken together, our results showed the involvement of the identified proteins in the Rs stress tolerance in potato. In the future, it would be interesting to raise the transgenic plants to further validate their involvement in resistance against Rs in potato. PMID- 26889113 TI - Population Analysis of Iranian Potato virus Y Isolates Using Complete Genome Sequence. AB - In this study, the full-length nucleotide sequences of four Iranian PVY isolates belonging to PVY(N) strain were determined. The genome of Iranian PVY isolates were 9,703-9,707 nucleotides long encoding all potyviral cistrons including P1, HC-Pro, P3, 6K1, CI, 6K2, VPg, NIa-Pro, NIb and CP with coding regions of 825, 1,395, 1,095, 156, 1,902, 156, 564, 732, 1,557 and 801 nucleotides in length, respectively. The length of pipo, embedded in the P3 cistron, was 231 nucleotides. Phylogenetic analysis showed that the Iranian isolates clustered with European recombinant NTN isolates in the N lineage. Recombination analysis demonstrated that Iranian PVY(N) isolates had a typical European PVY(NTN) genome having three recombinant junctions while PVY(N) and PVY(O) were identified as the parents. We used dN/dS methods to detect candidate amino acid positions for positive selection in viral proteins. The mean omega ratio differed among different genes. Using model M0, omega values were 0.267 (P1), 0.085 (HC-Pro), 0.153 (P3), 0.050 (CI), 0.078 (VPg), 0.087 (NIa-pro), 0.079 (NIb) and 0.165 (CP). The analysis showed different sites within P1, P3 and CP were under positive selection pressure, however, the sites varied among PVY populations. To the best of our knowledge, our analysis provides the first demonstration of population structure of PVY(N) strain in mid-Eurasia Iran using complete genome sequences and highlights the importance of recombination and selection pressure in the evolution of PVY. PMID- 26889114 TI - Diversity in Betasatellites Associated with Cotton Leaf Curl Disease During Source-To-Sink Movement Through a Resistant Host. AB - Cotton leaf curl is devastating disease of cotton characterized by leaf curling, vein darkening and enations. The disease symptoms are induced by DNA satellite known as Cotton leaf curl Multan betasatellite (CLCuMuB), dominant betasatellite in cotton but another betasatellite known as Chili leaf curl betasatellite (ChLCB) is also found associated with the disease. Grafting experiment was performed to determine if host plant resistance is determinant of dominant population of betasatellite in cotton (several distinct strains of CLCuMuB are associated with the disease). Infected scion of Gossypium hirsutum collected from field (the source) was grafted on G. arboreum, a diploid cotton species, resistant to the disease. A healthy scion of G. hirsutum (sink) was grafted at the top of G. arboreum to determine the movement of virus/betasatellite to upper susceptible scion of G. hirsutum. Symptoms of disease appeared in the upper scion and presence of virus/betasatellite in the upper scion was confirmed via molecular techniques, showing that virus/betasatellite was able to move to upper scion through resistant G. arboreum. However, no symptoms appeared on G. arboreum. Betasatelites were cloned and sequenced from lower scion, upper scion and G. arboreum which show that the lower scion contained both CLCuMuB and ChLCB, however only ChLCB was found in G. arboreum. The upper scion contained CLCuMuB with a deletion of 78 nucleotides (nt) in the non-coding region between A-rich sequence and betaC1 gene and insertion of 27 nt in the middle of betaC1 ORF. This study may help in investigating molecular basis of resistance in G. arboreum. PMID- 26889115 TI - Development of a Multiplex PCR Method to Detect Fungal Pathogens for Quarantine on Exported Cacti. AB - Major diseases in grafted cacti have been reported and Fusarium oxysporum, Bipolaris cactivora, Phytophthora spp. and Collectotrichum spp. are known as causal pathogens. These pathogens can lead to plant death after infection. Therefore, some European countries have quarantined imported cacti that are infected with specific fungal pathogens. Consequently, we developed PCR detection methods to identify four quarantined fungal pathogens and reduce export rejection rates of Korean grafted cacti. The pathogen specific primer sets F.oF-F.oR, B.CF B.CR, P.nF-P.nR, and P.cF-P.CR were tested for F. oxysporum, B. cactivora, P. nicotinae, and P. cactorum, respectively. The F.oF-F.oR primer set was designed from the Fusarium ITS region; the B.CF-B.CR and P.nF-P.nR primers respectively from Bipolaris and Phytophthora ITS1; and the P.cF-P.CR primer set from the Ypt1protein gene region. The quarantine fungal pathogen primer pairs were amplified to the specific number of base pairs in each of the following fungal pathogens: 210-bp (F. oxysporum), 510-bp (B. cactivora), 313-bp (P. nicotinae), and 447-bp (P. cactorum). The detection limit for the mono- and multiplex PCR primer sets was 0.1 ng of template DNA under in vitro conditions. Therefore, each primer set successfully diagnosed contamination of quarantine pathogens in export grafted cacti. Consequently, our methodology is a viable tool to screen contamination of the fungal pathogen in exported grafted cacti. PMID- 26889116 TI - Evaluation of Resistance to Ralstonia solanacearum in Tomato Genetic Resources at Seedling Stage. AB - Bacterial wilt of tomatoes caused by Ralstonia solanacearum is a devastating disease that limits the production of tomato in Korea. The best way to control this disease is using genetically resistant tomato plant. The resistance degree to R. solanacearum was evaluated for 285 tomato accessions conserved in the National Agrobiodiversity Center of Rural Development Administration. These accessions of tomato were originated from 23 countries. Disease severity of tomato accessions was investigated from 7 days to 14 days at an interval of 7 days after inoculation of R. solanacearum under greenhouse conditions. A total of 279 accessions of tomato germplasm were susceptible to R. solanacearum, resulting in wilt and death in 70 to 90% of these plants. Two tomato accessions were moderately resistant to R. solanacearum. Only four accessions showed high resistance against R. solanacearum. No distinct symptom of bacterial wilt appeared on the resistant tomato germplasms for up to 14 days after inoculation of R. solanacearum. Microscopy of resistant tomato stems infected with R. solanacearum revealed limited bacterial spread with thickening of pit membrane and gum production. Therefore, these four resistant tomato germplasms could be used in tomato breeding program against bacterial wilt. PMID- 26889117 TI - Identification of Leonurus sibiricus as a Weed Reservoir for Three Pepper Infecting Viruses. AB - In plant virus ecology, weeds are regarded as wild reservoirs of viruses and as potential sources for insect-mediated transmission of viruses. During field surveys in 2013-2014, three Leonurus sibiricus plants showing virus-like symptoms were collected from pepper fields in Daegu, Seosan, and Danyang in Korea. Molecular diagnosis assays showed that the collected L. sibiricus samples were infected with either Tomato spotted wilt virus (TSWV), Pepper mild mottle virus (PMMoV), or Beet western yellow virus (BWYV), respectively. Since this is the first identification of TSWV, PMMoV, and BWYV from L. sibiricus, complete genome sequences of three virus isolates were determined to examine their phylogenetic relationships with the previously reported strains and isolates. Phylogenetic analyses performed using full genome sequences of the viruses showed the isolates of TSWV and PMMoV obtained from L. sibiricus are closely related to the pepper isolates of the corresponding viruses. Our results suggest that L. sibiricus could act an alternative host and reservoir of viruses that cause damages in pepper fields. PMID- 26889118 TI - Establishment of a Simple and Rapid Gene Delivery System for Cucurbits by Using Engineered of Zucchini yellow mosaic virus. AB - The infectious full-length cDNA clone of zucchini yellow mosaic virus (ZYMV) isolate PA (pZYMV-PA), which was isolated from pumpkin, was constructed by utilizing viral transcription and processing signals to produce infectious in vivo transcripts. Simple rub-inoculation of plasmid DNAs of pZYMV-PA was successful to cause infection of zucchini plants (Cucurbita pepo L.). We further engineered this infectious cDNA clone of ZYMV as a viral vector for systemic expression of heterologous proteins in cucurbits. We successfully expressed two reporter genes including gfp and bar in zucchini plants by simple rub-inoculation of plasmid DNAs of the ZYMV-based expression constructs. Our method of the ZYMV based viral vector in association with the simple rub-inoculation provides an easy and rapid approach for introduction and evaluation of heterologous genes in cucurbits. PMID- 26889119 TI - Urological Manifestations of Placenta Percreta. AB - Placenta percreta is a condition of pregnancy associated with abnormal decidua placenta. It is characterized by invasion of chorionic villi past the myometrium and serosa, towards urogenital organs. Complications include massive hemorrhage, bladder dysfunction, and severe infections during delivery. Reports suggest an increasing prevalence of this condition. From a urological perspective, this review suggests how early diagnostic modalities, effective treatment plans, and appropriate surgical methods may aid in decreasing the morbidity and mortality of placenta percreta. The importance of maintaining bladder integrity during hysterectomy is emphasized. PMID- 26889121 TI - Additional Midline Biopsies of the Peripheral Zone Associated with the First Endorectal Standard Sextant Pattern Improves the Accuracy of Prostate Cancer Detection in Japanese Patients. AB - OBJECTIVES: This study was designed to estimate the improved accuracy of prostate cancer (PCa) detection resulting from additional midline biopsies of the peripheral zone in first standard biopsy. PATIENTS AND METHODS: Patients were classified into 3 groups: 402 cases of sextant biopsies (1995-2002), 488 cases of 8-core biopsies with 2 additional midline biopsies (2003-2006), and 391 cases of 10-core biopsies with 4 additional midline biopsies (2007-2012). The positive rate of each number of biopsies and changes in positive rates associated with prostate specific antigen (PSA) ranges were estimated. RESULTS: The positive rate of core biopsy significantly improved with increasing numbers of core biopsies (30.1% for sextant, 43.4% for 8-core biopsies, and 53.1% for 10-core biopsies). The accuracy of biopsies for each PSA range also significantly improved (22.3% for sextant, 30.0% for 8-core biopsies, and 43.2% for 10-core biopsies in the PSA gray zone [4.01-10 ng/ml]; and 26.5% for sextant, 52.9% for 8-core biopsies, and 71.8% for 10-core biopsies in the intermediate PSA range [10.1-20 ng/ml]). In the 208 cases with positive results using the 10-core biopsy method, the distribution of Gleason scores did not differ between the sextant only group and the midline site only group. CONCLUSIONS: Additional midline biopsy was associated with improved accuracy of positive core biopsies in Japanese patients with a PSA range of 4.01-20 ng/ml. (c) 2015 S. Karger AG, Basel. PMID- 26889120 TI - Urological Manifestations of Henoch-Schonlein Purpura: A Review. AB - Henoch-Schonlein purpura (HSP) is an immune-mediated systemic vasculitis generally found in children. The standard manifestations of HSP are palpable purpura, arthritis, abdominal pain, and renal complications. Although less common, there are significant urological manifestations associated with HSP. The primary objective of this review is to encourage better understanding and management of HSP by emphasizing the common and rare manifestations of HSP, how they are diagnosed, and the latest treatment options for mild to severe complications. Medline searches of HSP and its urological manifestations were conducted along with searches on current diagnostic and treatment methods. Urological manifestations of HSP involve the kidney, ureter, bladder, prostate, scrotum, testicle, and penis. Diagnosis and management of HSP are not always clear due to differential diagnosis and diversity of symptom presentation. Treatment for HSP is mainly supportive and includes use of nonsteroidal anti inflammatory drugs for pain relief. In more severe cases, glucocorticoids, methylprednisolone, plasmapheresis, and peritoneal and hemodialysis are reported successful. It is important to note different symptoms of HSP in order to distinguish HSP from other diseases. Early diagnosis may prevent severe complications. Treatment options vary from conservative to invasive depending on the severity of the disease and time frame of diagnosis. PMID- 26889122 TI - Predicting Acute Urinary Retention in Patients with Elevated Post-Void Residuals. AB - OBJECTIVES: To perform a retrospective analysis evaluating factors that may predict which men with elevated post-void residuals (PVRs) that were at increased risk to develop acute urinary retention (AUR). METHODS: We retrospectively analyzed the records of 44 male patients who had 2 consecutive PVRs greater than 100 ml over a 6-month period. Using regression analysis, we evaluated patient's age, PVR volume, prostate specific antigen (PSA) and transrectal ultrasound prostate volume with respect to development of AUR over 24 months. RESULTS: Of the 44 patients, 4 developed AUR. When all factors were considered, prostate volume was determined to be the only that was statistically significant (p = 0.003). A 1-SD increase in prostate volume (12 ml) led to a 19.6% increased risk of developing AUR. There was a strong correlation between PSA and prostate volume (0.787). A regression analysis was then repeated excluding prostate volume. PSA then became a statistically significant predictor of AUR (p = 0.007). A 1-SD increase in PSA (1.377 ng/ml) increased the patients' risk of developing AUR by 12.3%. CONCLUSION: In men with an elevated PVR, increased transrectal ultrasound prostate volume or PSA may help predict which patients have an elevated risk of developing AUR within the next 24 months. This information may influence which patients need early surgical intervention versus medical therapy. PMID- 26889123 TI - Oncological Outcomes in Japanese Men Undergoing Orchiectomy for Stage I Testicular Germ Cell Tumor. AB - BACKGROUND: The objective of this study was to retrospectively review oncological outcomes in patients with stage I testicular germ cell tumor (GCT). PATIENTS AND METHODS: This study included 265 consecutive Japanese men undergoing orchiectomy for stage I testicular GCT, and a retrospective review of their records was performed. RESULTS: Of these 265 patients, 192 and 73 were pathologically classified with seminoma and nonseminoma, respectively. Prophylactic radiation and chemotherapy were performed in 62 patients with seminoma and 6 with nonseminoma, respectively. Disease recurrence occurred in 12 seminoma patients, of whom 11 had not received prophylactic radiation therapy; however, all 12 achieved a complete response to bleomycin, etoposide and cisplatin therapy. Of the nonseminoma patients, 19 experienced disease recurrence and were then treated with bleomycin, etoposide and cisplatin followed additionally by the surgical resection of residual tumors and salvage chemotherapy in 7 and 4, respectively. There was no cancer-specific death in the 265 patients, and 5-year recurrence free survival rates in patients with seminoma and nonseminoma were 92.6 and 72.8%, respectively. Furthermore, following factors appeared to be significantly associated with recurrence-free survival in these patients: age, T classification, microvascular invasion and adjuvant therapy for those with seminoma, and microvascular invasion for those with nonseminoma. CONCLUSIONS: Despite a generally favorable prognosis in Japanese men with stage I testicular GCT, intensive follow-up or prophylactic therapy should be considered for men with possible risk factors of disease recurrence. PMID- 26889124 TI - Detection of Significant Prostate Cancer According to Anatomical Areas of Sampling Cores Obtained with Transrectal Systematic 12-Core Biopsy. AB - BACKGROUND: To analyze the diagnostic performance of 12-core biopsy in detecting significant prostate cancer (PCa). PATIENTS AND METHODS: Thisstudy included 206 PCa patients who underwent transrectal 12-core biopsy followed by radical prostatectomy. Radical prostatectomy specimens were anatomically divided into 12 areas according to the sampling cores, and the existence of significant cancer, defined by a tumor volume > 0.5 ml, was investigated. The detection rate of significant cancer in each area was calculated as follows: the number of positive core biopsies/the number of areas containing significant cancer * 100. RESULTS: The overall detection rate of significant cancer in all areas was 53.6%. The detection rate was significantly higher in the standard sextant cores than in the additional 6 cores in patients with prostate-specific antigen >= 10 ng/ml, clinical stage >= T2, or biopsy Gleason score >= 7, but not in those with prostate-specific antigen < 10 ng/ml, clinical stage T1c, or biopsy Gleason score <= 6. CONCLUSIONS: Approximately half of the significant cancers were not accurately detected, and the detection rates in biopsy cores other than the sextant cores appeared to be significantly lower in PCa patients with aggressive features. PMID- 26889125 TI - mp-MRI Prostate Characterised PIRADS 3 Lesions are Associated with a Low Risk of Clinically Significant Prostate Cancer - A Retrospective Review of 92 Biopsied PIRADS 3 Lesions. AB - OBJECTIVE: To determine whether prostate image reporting and data system (PIRADS) 3 lesions as assessed by a 3T multiparametric magnetic resonance imaging (MRI) represent clinically significant prostate cancer. METHOD: A retrospective review was performed on a series of consecutive patients who underwent MRI guided biopsy of the prostate for clinical suspicion of prostate cancer between January 2013 and March 2014. Demographic, clinical, MRI and biopsy data were reviewed and compared. The same 3T MRI without the use of an endo-rectal coil was employed to assess each patient, obtaining high resolution T2 weighted images, diffusion weighted imaging and dynamic contrast enhancement. The MRI data was sent to Dynacad software for analysis. A single experienced radiologist reported all the studies from this series using a modified PIRADS scoring system. Subsequently, all the lesions marked PIRADS 3 or above were targeted with 18G core biopsy using DynaTrim in-gantry MRI guidance system. Needle position targeting the lesion was recorded prior to each biopsy. All core biopsy samples were sent to one of two pathology laboratories where they were processed and reported as per the International Society of Urological Pathology protocols. RESULTS: One hundred and eighteen patients comprising a total of 215 lesions were reviewed. Amongst this cohort, 92 PIRADS 3 lesions were identified and biopsied. The mean age of patients in this cohort was 62.6 years. Median prostate specific antigen (PSA) was 6.5 ng/ml and median prostate size was 78.4 ml. Eightysix (93.5%) of biopsied PIRADS 3 lesions were benign and 6 (6.5%) lesions were found to be malignant. Of these 6 malignant lesions, 4 (66%) were Gleason score 6 (3 + 3) and 2 (33%) were Gleason score 7 (3 + 4). Of the 86 non-malignant lesions, 1 (1.2%) represented high-grade prostate intraepithelial neoplasia and 2 (2.4%) represented atypical small acinar proliferation. PIRADS 3 lesions within the peripheral zone were more likely to be associated with malignant disease compared with lesions identified within the transition zone (10.8 vs. 3.8%). Those with malignant disease had a higher median PSA (8.1 vs. 6.4 ng/ml) and higher median PSA density (0.12 vs. 0.08) than those without malignant disease. Those with benign pathology had a higher prevalence of inflammation (31.4 vs. 16.7%). As per Epstein's criteria, 4 (4.3%) of the biopsied lesions represented clinically significant disease. CONCLUSION: We have demonstrated in our series, that prostate lesions characterized on a 3T multiparametric MRI examination of the prostate as PIRADS 3, according to the current prevalent scoring systems, are associated with a low likelihood of the presence of clinically significant prostate cancer. PMID- 26889126 TI - Case Report: Conversion of a Low-Flow to High-Flow Priapism. AB - Priapism is defined as an erection lasting for more than 4 hours and can be grouped into 3 distinct subtypes: ischemic (low-flow), stuttering and non ischemic (high-flow). Herein, we present an interesting case of conversion from a low-flow to high-flow priapism after a distal shunting procedure. This is a rare phenomenon that has a paucity of documented cases. Diagnosis requires prompt clinical suspicion and confirmatory testing including penile cavernosal blood gases and Doppler ultrasound. PMID- 26889127 TI - Robot-Assisted Laparoscopic Bladder Diverticulectomy and Ureteral Re-Implantation for a Diverticulum Containing High Grade Transitional Cell Carcinoma. AB - We present a case of an 84-year-old man presenting with painless visible hematuria. Further investigation revealed a primary G3pT1 transitional cell carcinoma confined to a bladder diverticulum. In view of bladder-sparing therapy, he underwent a robot-assisted laparoscopic bladder diverticulectomy with ureteral re-implantation. This report demonstrates a minimally invasive approach offering radical treatment without having to recur to partial or radical cystectomy. We discuss the operative steps, the significance of this case with a review of the literature, and the future potential this may represent for the treatment of tumor-containing bladder diverticula. PMID- 26889128 TI - Angiosarcoma of the Prostate Gland following Brachytherapy for Prostatic Adenocarcinoma. AB - Prostatic adenocarcinoma is the most common cancer in men, but only a handful of cases of prostatic angiosarcoma have been reported in the literature. Prior radiation therapy for prostatic adenocarcinoma has been hypothesized to be a risk factor for angiosarcoma. The increasing practice of prostate cancer screening and the use of radiation therapy for management of prostatic adenocarcinoma will likely lead to more cases of prostatic angiosarcoma. Diagnosis is made by tissue sampling. Optimal management of these aggressive tumors remains to be defined and outcomes are poor with a high 1-year mortality. Primary care physicians and urologists should be aware of this rare entity and refer these patients to specialist centers where they can be managed by a multidisciplinary team. We report a case of angiosarcoma of the prostate gland diagnosed in a male presenting with lower urinary tract symptoms 5 years after brachytherapy for prostate adenocarcinoma. PMID- 26889129 TI - Melatonin and Its Role in Lower Urinary Tract Function: An Article Review. AB - This article reviewed the results of studies done on animals that assessed effects of melatonin on bladder function. Melatonin does not change strip relaxation on its own. However, pre-treatment with melatonin decreases contractile responses induced by phenylephrine, acetylcholine, bethanechol and KCl in a dose-dependent manner. The contractile responses induced by the direct calcium channel openers are significantly decreased by melatonin pre-treatment. It also binds to Ca(2+)-activated calmodulin, and prevents it from activating myosin light-chain kinase. It may have direct effects on ion channels which are responsible for regulating bladder contraction. Its other mode of action on bladder occurs via the brain GABAA receptor. Melatonin is an antioxidant. In bladder, treatment with melatonin prevents elevations in malondialdehyde levels, reverses changes in glutathione levels, and decreases myeloperoxidase levels compared with oxidative injury. It can normalize age induced bladder dysfunction through its antioxidant effects, inhibiting smooth muscle contractility directly and restoring impaired contractility via normalization of Ca(2+) handling and sensitizations pathways. It attenuates the severity of cystitis and inflammation. Mast cell proliferation and activation are increased in cystitis, but decrease by melatonin treatment. Also, there is a decrease in expression levels of pro inflammatory cytokines after melatonin treatment. PMID- 26889130 TI - Effect of Polyuria on Bladder Function in Diabetics versus Non-Diabetics: An Article Review. AB - OBJECTIVES: To review studies that investigated the role of polyuria on bladder function. METHODS: We performed a search of the English literature through PubMed. We only included animal studies that assessed parameters of bladder function and had compared diabetic and non-diabetic polyuric animals. RESULTS: Fluid intake and urine output were increased in diabetic and polyuric animals; failure to appropriately gain weight was seen in diabetics only. All but 1 study reported increase in bladder weight in both groups. In cystometrograms, control mice showed reductions in basal bladder pressure over time, whereas diabetic and diuretic groups stabilized or increased. Both groups showed larger bladder capacity. Overall, many characteristic changes in cystometrographic studies in diabetic animals could be attributed to polyuria. In histological studies, bladder hypertrophy, increase in smooth muscle and urothelium, and increase in protein and DNA content per bladder were observed in diuretic and diabetic rats. Actual collagen cross-sectional area did not change during the progression of diabetes or diuresis but decreased over time in both groups as a percentage of total tissue area. Both groups expressed less type I collagen mRNA and TGF-beta-1 mRNA. CONCLUSIONS: Although lower urinary tract changes in anatomy and function in diabetic patients might arise from a number of causes, polyuria seems to play an important causative role. PMID- 26889131 TI - Influence of Demographic and Clinical Factors on Surgical Outcomes of the Transobturator Tape Procedure in Patients with Stress Urinary Incontinence. AB - BACKGROUND: Stress urinary incontinence (SUI) is a prevalent problem within the female population with associated high psycho-social impact. Transobturator tape procedure is a well-established procedure to treat the same, but the results may be influenced by various preoperative demographic and clinical factors. PATIENTS AND METHODS: The study group comprised of 50 female patients with genuine SUI, who were then divided into subgroups based on demographic and clinical factors. Outcomes were compared between these subgroups at 6 and 12 months using self reported questionnaires and provocative stress test. RESULTS: Our results show positive correlation with statistically significant better surgical outcomes in premenopausal patients, patients aged <50 years and those having urethral mobility > 30 degrees. Statistically significant poor outcomes were seen in those having undergone hysterectomy or Caesarean section. No correlation was found with history of smoking or the patient's body mass index. CONCLUSIONS: In conclusion, the transobturator tape procedure appears to be more effective in premenopausal women, women aged < 50 years, women without history of hysterectomy/lower section Caesarean section, and presence of urethral hypermobility > 30 degrees. On the other hand, outcomes do not appear to be influenced by the patient's body mass index or smoking status. PMID- 26889132 TI - Renal Trauma: The Rugby Factor. AB - INTRODUCTION: Renal trauma accounts for 5% of all trauma cases. Rare mechanisms of injuries including sports participation are increasingly common. Rugby-related trauma poses a conundrum for physicians and players due to the absence of clear guidelines and a paucity of evidence. Our series highlights traumatic rugby related renal injuries in our institution, and emphasize the need for international guidelines on management. METHODS: A retrospective review of all abdominal traumas between January 2006 and April 2013, specifically assessing for renal related trauma that were secondary to rugby injuries was performed. All patients' demographics, computerized tomography results, hematological and biochemical results and subsequent management were recorded. RESULTS: Five male patients presented with rugby-related injuries. Mean age was 21 years old. All patients were hemodynamically stable and managed conservatively in acute setting. One patient was detected to have an unknown pre-existing atrophic kidney that had been subsequently injured, and was booked for an elective nephrectomy an 8-week interval. CONCLUSION: Rugby-related trauma has generated essential attention. This paper serves to highlight this type of injury and the need for defined guidelines on role of imaging and international consensus on timing of return to contact sport, in both professional and amateur settings. PMID- 26889133 TI - Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors. AB - OBJECTIVES: To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. METHODS: One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. RESULTS: Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09-23.34, one tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. CONCLUSIONS: This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa. PMID- 26889134 TI - Changes in Urolithiasis Referral Patterns for Shock Wave Lithotripsy over a Decade: Was There Adherence to AUA/EAU Guidelines? AB - OBJECTIVE: The primary objective was to assess changes in referral patterns of urolithiasis for shock wave lithotripsy (SWL) over a decade. The secondary objective was to evaluate the effect of the number of years of practice of referring physicians on these referral patterns. METHODS: A retrospective review of SWL database was performed for consecutive referrals for SWL at a tertiary stone center between December 1999 and December 2013. Patient demographics and stone characteristics were assessed. The stone location at the time of referral was used as the reference. Retreatments were excluded. In addition, years of practice of the referring physicians were calculated. The 2007 AUA/EAU guidelines on urolithiasis were considered as a reference. RESULTS: A total of 8,992 SWL treatments were included. After December 2007, there was a significant increase in the percentage of renal pelvic stones referred for SWL (23.0 vs. 27.1%, p < 0.001). Conversely, proximal ureteral stones significantly decreased after 2007 (24 vs. 18.2%, p < 0.001) including stones > 10 mm (5.1 vs. 2.9%, p < 0.001). Otherwise, there were no changes in the referral patterns for SWL of other stone locations before and after December 2007 (p > 0.05). Furthermore, percentage of stones referred for SWL by urologists practicing for less than 10 years significantly decreased after December 2007 (29.5 vs. 22.8%, p < 0.001). CONCLUSIONS: The significant reduction in the referral of proximal ureteral stones after December 2007 corresponds to the latest AUA/EAU guidelines on management of ureteral stones. PMID- 26889135 TI - Impact of Obesity on Complications of Laparoscopic Simple or Radical Nephrectomy. AB - OBJECTIVE: To determine the impact of obesity on complications in laparoscopic simple or radical nephrectomy. PATIENTS AND METHODS: The medical files of 215 patients who underwent laparoscopic simple or radical nephrectomy in our center between 2004 and 2014 were reviewed. A body mass index of 30 kg/m2 was used to divide the patients into obese and non-obese groups. Pre-operative data and intra and post-operative complications were compared between the 2 groups. RESULTS: There were respectively 163 and 52 patients in the non-obese and obese groups, which were comparable in terms of age, sex, and history of surgery. In the obese group, operative specimens were significantly heavier (772 vs. 534 g in the non obese group; p = 0.005) and durations of surgery was significantly longer (244 vs. 216 minutes; p = 0.003). However no significant differences were found between the 2 groups for duration of hospitalization, surgical conversion, estimated blood loss, or intra- or post-operative complications. CONCLUSION: Laparoscopic simple or radical nephrectomy is technically feasible in obese patients but the surgery may take more time, notably due to dissection difficulties. Our results showed that the risk of intra- and post-operative complications is not higher in obese patients compared to non-obese patients, except for a possible, but statistically undemonstrated, higher risk of abdominal wall complications, and that the laparoscopic approach should be the preferred technique in patients with high body mass index. PMID- 26889137 TI - Xanthogranulomatous Pyelonephritis with Staghorn Calculus, Acute Gangrenous Appendicitis and Enterocolitis: A Multidisciplinary Challenge of Kidney Preserving Conservative Therapy. AB - Xanthogranulomatous pyelonephritis (XP) is a rare form of pyelonephritis and without treatment destructive to the kidney. We describe a 74-year-old Caucasian immunocompetent female patient with XP and multiple abscesses on the upper pole of the right kidney and several impacted obstructing renal calculi in the middle calyx that developed severe colitis and gangrenous appendicitis during therapy. Proteus mirabilis was detected as the major pathogen in the urine culture. Kidney preserving therapy was carried out by intensive parenteral bacterial eradication, CT-guided abscess drainage and stone destruction by 3 sessions of extracorporeal shock wave lithotripsy under ureteral stenting. Large tumor masses in XP are often daunting and may lead to a nephrectomy. However, kidney-preserving therapy is possible and should be considered in non-septic patients or in case of a solitary kidney. PMID- 26889138 TI - Incidentally-Discovered Squamous Cell Carcinoma after Endoscopic Sphincterotomy. AB - The association between the development of bladder cancer and chronic bladder irritation is well established in the literature. Chronic urinary tract irritation can be the result of bacterial infections, foreign bodies, trauma of repeated catheterization, neurogenic bladder, urolithiasis, or chronic bladder outlet obstruction, all which have been implicated in the pathogenesis of non bilharzial squamous cell carcinoma of the bladder (SCC). With many of the aforementioned factors present in patients with spinal cord injury, several retrospective studies have demonstrated a 16-28 fold increased relative risk of bladder cancer, with SCC accounting for 10 times more cases of bladder cancer compared to the general population. In this report, we present the case of incidentally-discovered SCC of the bladder found within sphincter/prostate chips of a patient with neurogenic bladder due to spinal cord injury n clean intermittent catheterization ho underwent sphincterotomy with negative cystoscopic findings. PMID- 26889136 TI - Open Versus Robotic Radical Prostatectomy in Obese Men. AB - OBJECTIVES: Robotic-assisted radical prostatectomy (RARP) has been shown to reduce blood loss, peri-operative complications and length of stay when compared to open radical prostatectomy (ORP). We sought to determine whether the reported benefits of RARP over ORP translate to obese patients. PATIENTS AND METHODS: We utilized the 2009-2010 Nationwide Inpatient Sample to identify all obese men with prostate cancer who underwent ORP and RARP. Our primary outcome was the presence of a peri-operative adverse event (i.e. blood transfusion, complication, prolonged length of stay). We fit multivariable logistic regression models to examine whether RARP in obese patients was independently associated with decreased odds of all three outcomes. RESULTS: We identified 9,108 obese patients who underwent radical prostatectomy. On multivariable analysis, the use of RARP in the obese population was not independently associated with decreased odds of developing a peri-operative complication (OR = 0.81, CI: 0.58-1.13, p = 0.209). RARP was, however, associated with decreased odds of blood transfusion (OR = 0.17, CI: 0.10-0.30, p < 0.001) and prolonged length of stay (OR = 0.28, CI: 0.20 0.40, p < 0.001). CONCLUSION: Our findings suggest that in obese patients, the use of RARP may reduce length of stay and blood transfusions compared to ORP. Both approaches, however, are associated with similar odds of developing a complication. PMID- 26889139 TI - Scald-Induced Necrobiosis Lipoidica in a Patient with Diabetes Mellitus and Psoriasis. AB - The Koebner phenomenon (KP) was first introduced by Heinrich Koebner in the 1870s to describe the appearance of psoriatic lesions following trauma in psoriasis patients. KP has since been defined in numerous diseases, including necrobiosis lipoidica diabeticorum (NLD). Since most Koebnerized dermatological lesions can localise to a site of previous trauma, Weiss et al. (Eur Acad Dermatol Venereol 2002;16:241-248) classified them into four categories (I-IV) according to the Boyd-Nelder classification (Int J Dermatol 1990;29:401-410) system. In this system, necrobiosis lipoidica is classified as category III, which includes diseases that occasionally localise at the site of trauma. We report a case of NLD that developed after scald in a psoriasis patient. NLD after trauma has often been reported, but this is the first case of NLD that coincidentally occurred at a scald site in a psoriasis patient. PMID- 26889140 TI - Treatment of Non-Colorectal Liver Metastases. PMID- 26889141 TI - Morphologic and Functional Imaging of Non-Colorectal Liver Metastases. AB - Liver metastases are the most frequent malignant liver lesions. Besides colorectal carcinoma, gastric carcinoma, pancreatic carcinoma, breast cancer, lung cancer, and neuroendocrine tumors are the most common entities that metastasize to the liver. The morphology of these metastases depends on the primary tumor. For morphologic and functional imaging of non-colorectal liver metastases, multiple imaging techniques such as ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography coupled with CT or MRI are available. This review summarizes morphologic and functional characteristics of different non-colorectal liver metastases. PMID- 26889143 TI - Is There a Role for Liver Transplantation in Non-Colorectal Liver Metastases? AB - Due to the high blood flow, especially blood from the intestinal tract via the portal vein, the liver is a preferred organ for metastases. In case of advanced, irresectable liver metastases liver transplantation (LTX) remains an attractive option. However, due to high recurrence rates or a lack of data, up to date, metastases from neuroendocrine tumors (NETs) are the only accepted indication for LTX in non-colorectal liver metastases. In this regard, LTX is only justified in patients in which complete tumor resection (R0 resection) of the NET is achievable. A literature review revealed no clear patient selection criteria but transplantation should definitively achieve an R0 resection with complete freedom of tumor. The available data regarding the outcome following LTX for NETs show a comparable short- and long-term outcome for patients transplanted for other malignancies, e.g. hepatocellular carcinoma, or also benign indications in the high MELD (model for end-stage liver disease) era. Thus, most data prove a better post-transplant outcome and a lower recurrence rate in patients with a good differentiation of the tumor, a low proliferation index (Ki67), and a portal drainage of the NET. PMID- 26889142 TI - Liver Resection for Non-Colorectal Liver Metastases - Standards and Extended Indications. AB - BACKGROUND: Due to the uncertain benefit of liver resection for non-colorectal liver metastases (NCLM), patient selection for surgery is generally difficult. Therefore, the aim of this article was to propose standard and extended indications for liver resection in this heterogeneous disease collective. METHODS: Review of the literature. RESULTS: The myriad of biologically different primary tumor entities as well as the mostly small and retrospective studies investigating the benefit of surgery for NCLM limits the proposal of general recommendations. Only resection of neuroendocrine liver metastases (NELM) appears to offer a clear benefit with a 5- and 10-year overall survival (OS) of 74 and 51%, respectively, in the largest series. Resection of liver metastases from genitourinary primaries might offer reasonable benefit in selected cases - with a 5-year OS of up to 61% for breast cancer and of 38% for renal cell cancer. The long-term outcome following surgery for other entities was remarkably poorer, e.g., gastric cancer, pancreatic cancer, and melanoma reached a 5-year OS of 20 42, 17-25, and about 20%, respectively. CONCLUSION: Liver resection for NELM can be defined as a standard indication for the resection of NCLM while lesions of genitourinary origin might be defined as an extended indication. PMID- 26889144 TI - How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non Colorectal Liver Metastases? AB - BACKGROUND: The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. METHODS: Liver directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: 'image guided tumor ablation', 'thermal ablation therapies', 'liver metastases of uveal melanoma', 'neuroendocrine carcinoma', 'breast cancer', and 'non-colorectal liver metastases'. RESULTS: Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. CONCLUSION: Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID- 26889145 TI - Arterial Therapies of Non-Colorectal Liver Metastases. AB - BACKGROUND: The unique situation of the liver with arterial and venous blood supply and the dependency of the tumor on the arterial blood flow make this organ an ideal target for intrahepatic catheter-based therapies. Main forms of treatment are classical bland embolization (TAE) cutting the blood flow to the tumors, chemoembolization (TACE) inducing high chemotherapy concentration in tumors, and radioembolization (TARE) without embolizing effect but very high local radiation. These different forms of therapies are used in different centers with different protocols. This overview summarizes the different forms of treatment, their indications and protocols, possible side effects, and available data in patients with non-colorectal liver tumors. METHODS: A research in PubMed was performed. Mainly clinical controlled trials were reviewed. The search terms were 'embolization liver', 'TAE', 'chemoembolization liver', 'TACE', 'radioembolization liver', and 'TARE' as well as 'chemosaturation' and 'TACP' in the indications 'breast cancer', 'neuroendocrine', and 'melanoma'. All reported studies were analyzed for impact and reported according to their clinical relevance. RESULTS: The main search criteria revealed the following results: 'embolization liver + breast cancer', 122 results, subgroup clinical trials 16; 'chemoembolization liver + breast cancer', 62 results, subgroup clinical trials 11; 'radioembolization liver + breast cancer', 37 results, subgroup clinical trials 3; 'embolization liver + neuroendocrine', 283 results, subgroup clinical trials 20; 'chemoembolization liver + neuroendocrine', 202 results, subgroup clinical trials 9; 'radioembolization liver + neuroendocrine', 64 results, subgroup clinical trials 9; 'embolization liver + melanoma', 79 results, subgroup clinical trials 15; 'chemoembolization liver + melanoma', 60 results, subgroup clinical trials 14; 'radioembolization liver + melanoma', 18 results, subgroup clinical trials 3. The term 'chemosaturation liver' was tested without indication since only few publications exist and provided us with five results and only one clinical trial. CONCLUSION: Despite many years of clinical use and documented efficacy on intra-arterial treatments of the liver, there are still only a few prospective multicenter trials with many different protocols. To guarantee the future use of these efficacious therapies, especially in the light of many systemic or surgical therapies in the treatment of non-colorectal liver metastases, further large randomized trials and transparent guidelines need to be established. PMID- 26889146 TI - Current Medical Treatment of Patients with Non-Colorectal Liver Metastases: Primary Tumor Breast Cancer. AB - BACKGROUND: (Metastatic) breast cancer is a heterogeneous entity in which every disease subtype requires an individualized systemic treatment approach. METHODS: We reviewed the currently available data regarding systemic therapy of breast cancer and present a review of historical and current treatment approaches, with the publications cited covering a time span from 1896 to the last ASCO 2015. RESULTS: Systemic therapy of metastatic breast cancer may include chemotherapy, endocrine therapy, and targeted therapies (e.g. antibody-based approaches). Based on the patient's breast cancer subtype, these agents may be employed alone or in combination. Therefore, characterization of the phenotype of the disease is necessary and may include biopsy of the metastatic site. Novel therapeutic approaches include immunologic therapies as well as PARP, PI3K and CDK 4/6 inhibitors, which are currently under investigation in clinical trials. CONCLUSION: Systemic therapy of metastatic breast cancer requires complex and individualized treatment approaches that are best offered in an interdisciplinary setting. PMID- 26889147 TI - Precision Medicine and Non-Colorectal Cancer Liver Metastases: Fiction or Reality? AB - BACKGROUND: Non-colorectal liver metastases (nCRLM) constitute a variety of heterogeneous diseases and a considerable therapeutic challenge. Management is based on the primary tumor and the clinical course. In the era of precision medicine (PM) we know that cancer is heterogeneous within the tumor and across different sites. METHODS: We give an overview of the path to PM through 'omics' beyond genomics. We refer to the experience gained to date from models such as colorectal cancer and we discuss the opportunity offered by PM for the management of nCRLM. RESULTS: In order to best characterize and track tumor biological behaviors as well as to understand mechanisms of response to therapy and survival we suggest the application of novel clinical trial designs, a dynamic approach with serial monitoring involving evaluation of primary and metastatic sites. Quality and standardization of tissue acquisition and biobanking is a precondition for the reliability of this approach. CONCLUSION: The application of PM is increasingly becoming a reality. Elucidating the mysteries of tumors in complex settings can only be achieved with the approach PM offers. nCRLM may serve as a model for the application of PM principles and techniques in understanding individual diseases and also cancer as an entity and therapeutic challenge. PMID- 26889148 TI - Ectopic Spleen Tissue - an Underestimated Differential Diagnosis of a Hypervascularised Liver Tumour. AB - BACKGROUND: Patients with liver cirrhosis have an increased risk of developing hepatocellular carcinoma (HCC). Implantation metastasis following diagnostic biopsy is a well-known complication. Therefore, primary resection of a hypervascularised tumour suspicious for HCC is often performed with curative intent. CASE REPORT: An exophytically growing mass was diagnosed between liver segments III and IVb by means of ultrasound in a 53-year old male patient with decompensated liver cirrhosis. Computed tomography confirmed a 3.5 cm large hypervascularised tumour with given resectability. Intraoperatively, the tumour appeared like a HCC. Thus, an atypical resection was performed. Histopathology revealed ectopic spleen tissue without any signs of malignancy. As enquiries revealed, the patient had undergone splenectomy after a blunt abdominal trauma 9 years prior to admission. CONCLUSION: In the present patient, hepatic splenosis in a cirrhotic liver was misinterpreted as HCC. In patients with a history of traumatic rupture of the spleen or splenectomy, splenosis has to be considered as a potential differential diagnosis of a hypervascularised tumour. Specific diagnostics should be performed to rule out splenosis. PMID- 26889149 TI - Treatment with Tumor-Treating Fields Therapy and Pulse Dose Bevacizumab in Patients with Bevacizumab-Refractory Recurrent Glioblastoma: A Case Series. AB - Patients with bevacizumab-refractory recurrent glioblastoma multiforme (GBM) have a poor prognosis. We propose that instead of continuing on bevacizumab, patients should switch to treatment with OptuneTM, a novel antimitotic Tumor-Treating Fields (TTFields) therapy approved in the United States for newly diagnosed and recurrent GBM. This would reserve bevacizumab for subsequent disease progression. In this case series, we describe 8 patients with recurrent GBM who had disease progression on bevacizumab, discontinued bevacizumab treatment, and were treated with TTFields therapy alone. After subsequent radiographic or clinical progression, 5 patients were rechallenged with bevacizumab in a 'pulse dose' fashion, an approach not previously described. Following treatment with TTFields therapy, median overall survival (OS) was 216 days (7.2 months). Median OS from last dose of initial bevacizumab was 237 days (7.9 months), twice that of historical controls for bevacizumab failures, and median OS from the first dose of bevacizumab rechallenge was 172 days (5.7 months). TTFields therapy was well tolerated, with a mean adherence rate of 74.2% (range, 48.2-92.9%). These results support the use of TTFields therapy with pulse dose bevacizumab as an option in patients with refractory GBM. PMID- 26889151 TI - Paraneoplastic Choreoathetosis in a Patient with Small Cell Lung Carcinoma and Anti-CRMP5/CV2: A Case Report. AB - INTRODUCTION: The occurrence of more or less monosymptomatic paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies is rare. Typically, such autoantibodies are associated with a more classical syndrome - paraneoplastic encephalomyelitis. Frequently, small cell lung carcinoma (SCLC) is the related neoplastic finding. CASE REPORT: We present a 71-year-old woman who developed visual symptoms with papilledema and chorea. Anti-CRMP5/CV2 antibodies were a feature of both the serum and cerebrospinal fluid. Although SCLC was suspected already at the time of the initial examinations, no signs of primary or metastatic tumors were revealed on chest X-ray, MRI or whole-body PET scan. EEG and bronchoscopy were also unremarkable. However, 6 months after the onset, a repeated PET scan and subsequent bronchoscopic biopsy revealed SCLC. In spite of chemotherapy, the SCLC progressed, and the patient died 14 months after the onset of the symptoms. CONCLUSION: We report paraneoplastic choreoathetosis associated with anti-CRMP5/CV2 antibodies. Such published case histories are rare. Although expected, we did not find any reduced signal intensity at the basal ganglia on the T1-weighted or increased intensity on the T2-weighted MRI scans. PMID- 26889150 TI - Intracranial Hypertension as an Acute Complication of Aseptic Meningoencephalitis with Leptomeningeal Contrast Enhancement on FLAIR MRI. AB - We report a case of a 19-year-old woman who developed intracranial hypertension as an unusual clinical complication of severe aseptic meningoencephalitis probably due to a diminished cerebrospinal fluid reabsorption capacity or leptomeningeal transudation as a consequence of blood-brain barrier dysfunction. These severe inflammatory changes were accompanied by prominent leptomeningeal contrast enhancement best visualized on fluid-attenuated inversion recovery magnetic resonance imaging. In such a prolonged course, a continuous lumbar drainage might be a temporary option to provide rapid symptom relief to the patient. PMID- 26889152 TI - Pars Plana Vitrectomy Combined with Internal Limiting Membrane Peeling to Treat Persistent Macular Edema after Anti-Vascular Endothelial Growth Factor Treatment in Cases of Ischemic Central Retinal Vein Occlusion. AB - OBJECTIVE: To evaluate the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling in cases of ischemic central retinal vein occlusion (CRVO) where macular edema (ME) persisted after anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: Fifteen eyes with ischemic CRVO-related ME were included in the study. Nine were treated with panretinal photocoagulation after initial examination. Anti-VEGF agents were injected intravitreally. Persistent ME was treated with PPV combined with ILM peeling. During surgery, laser photocoagulation was further applied to the non perfused area. RESULTS: Mean retinal thickness gradually decreased after surgery (p = 0.024 at 6 months), although visual acuity did not improve significantly during the follow-up period (14.7 +/- 11.6 months). Neovascular glaucoma subsequently developed in three cases and a trabeculectomy was performed in one case. CONCLUSION: In eyes with ischemic CRVO, PPV combined with ILM peeling contributed to a reduction in persistent ME. However, there was no significant improvement in visual acuity. PMID- 26889153 TI - Peripheral Ulcerative Keratitis following Laser in situ Keratomileusis. AB - PURPOSE: We report a case of a patient with a history of glomerulonephropathy, not disclosed prior to laser in situ keratomileusis (LASIK), who developed severe postoperative peripheral ulcerative keratitis (PUK) soon after surgery. METHOD: Case report. RESULTS: Within a week of surgery, the patient, who had no blepharitis or ocular surface disease, also developed diffuse lamellar keratitis (DLK) that was not contiguous with the PUK. Microbiologic evaluation of the flap interface disclosed no organisms, and no epithelial ingrowth was found. Both PUK and DLK resolved with topical and oral steroid therapy, and the patient's induced refractive error improved over the 12 months following LASIK. CONCLUSIONS: Necrotizing keratitis has been described after LASIK surgery in patients with or without autoimmune disease. However, to our knowledge, there has been no case of PUK following LASIK. As shown by our patient's clinical course and the typical association of PUK with systemic conditions, patients with a history of atypical postinfectious sequelae may require additional preoperative counseling, vigilant postoperative monitoring, and possibly additional intervention. Because patients do not always divulge medical details, especially if an extraocular site was involved or illness occurred many years prior, this case demonstrates the importance of performing a diligent history that excludes autoimmune disorders or atypical postinfectious sequelae prior to proceeding with keratorefractive intervention. PMID- 26889154 TI - Right Homonymous Hemianopia: A Clinical Case Report of Schizencephaly. AB - PURPOSE: To report a case of a 56-year-old male with right homonymous hemianopia. METHODS: Retrospective descriptive study of a case report based on information from clinical records, patient observation and analysis of complementary diagnostic tests. RESULTS: An asymptomatic 56-year-old male presented to our hospital for a routine ophthalmic examination. The best-corrected visual acuity was 20/20 in the right eye (RE) and in the left eye (LE). Pupillary function, intraocular pressure, external segment examinations and slit-lamp biomicroscopy were normal, bilaterally. Fundoscopy showed a cup-to-disc (C/D) ratio in the RE of 0.3 and of 0.4 in the LE. Retinal nerve fiber layer (RNFL) thickness measured by spectral domain optical coherence tomography revealed thinning of the superior, temporal and nasal RNFL in the RE and thinning of the superior, inferior and temporal RNFL in the LE. Automated static perimetry showed right homonymous hemianopia. Brain computed tomography (CT) showed an open-lip schizencephaly with a significant reduction of the left brain parenchyma. CONCLUSIONS: Despite the large visual defect, the patient was unaware of it and had an active professional life. This is an interesting case because despite the extensive morphological abnormalities seen on brain CT there is a relatively small functional repercussion. PMID- 26889155 TI - Rhizopus Keratitis Associated with Poor Contact Lens Hygiene. AB - We report a case of Rhizopus keratitis in a young woman with poor contact lens hygiene. The mold was highly sensitive to treatment with amphotericin 0.15% drops, after a relatively prompt diagnosis. Obtaining cultures of both corneal infiltrates and presumably infected contact lenses may help to avoid a delay in proper treatment. PMID- 26889156 TI - Myeloid Sarcoma in an Eyelid That Developed during Chemotherapy for Acute Myeloid Leukemia. AB - An 80-year-old female presented with a mass in the left upper eyelid margin that had developed during chemotherapy for acute myeloid leukemia. The mass was elastic, hard, and pinkish, with a relatively smooth surface but without madarosis. The histopathological findings corresponded to a myeloid sarcoma. No blast cells were shown in the peripheral blood at the time of biopsy, and she subsequently underwent an azacitidine injection regimen. The size of the eyelid tumor decreased 3 months after the biopsy, when the course of azacitidine injections was completed. However, acute myeloid leukemia recurred, and the patient died. PMID- 26889157 TI - Anterior Segment Scleral Fluorescein Angiography in the Evaluation of Ciliary Body Neoplasm: Two Case Reports. AB - INTRODUCTION: Anterior segment tumors can be difficult to detect until tumor growth is substantial enough to cause local signs or symptoms. Earlier detection may result in improved outcomes, particularly the ability to option for globe conserving therapy. Multiple diagnostic modalities such as ultrasound or optical coherence tomography exist to aid for earlier detection of ciliary body tumors, but they also have limitations. Here we describe the potential for scleral angiography as an adjunctive modality to assist in evaluating anterior segment ciliary body tumors. CASE PRESENTATIONS: A 61-year-old Caucasian male and a 57 year-old Hispanic female presented for ciliary body tumor evaluation. The Caucasian male notably had abnormal scleral, episcleral, and conjunctival vessels in the affected eye. Scleral angiography was performed in both cases with the abnormal vasculature highlighted in the Caucasian male. The Hispanic female did not demonstrate abnormal scleral angiographic patterns. Notably, the Caucasian male also had regions of abnormal scleral angiography arising in locations of otherwise normal appearing sclera. Both patients had the affected eyes enucleated. Histology of the enucleated eyes demonstrated a ciliary body melanoma in the Caucasian male associated with abnormal vascular and tumor infiltration of the scleral bed. The Hispanic female had a pigmented ciliary body adenoma without involvement of the scleral bed. CONCLUSION: With limited sample size, scleral angiography has the potential to detect abnormal scleral vascular patterns in otherwise normal appearing sclera in cases of ciliary body tumor with scleral vascular invasion. PMID- 26889158 TI - Multimodal Imaging and Clinicopathologic Correlation in Primary Uveal Lymphoma. AB - PURPOSE: We report a rare case of primary uveal lymphoma and characterize it using histopathology and multimodal imaging. PATIENT AND METHODS: A 41-year-old male presented with a 2-year history of increasingly blurry vision in his right eye and no systemic symptoms. Examination revealed a retinal detachment and mass lesion in the right eye. Radiologic and histologic testing was performed. RESULTS: Multimodal imaging localized the lesion to the choroid, and fine needle aspiration biopsy diagnosed the lesion as a low-grade B-cell lymphoma. The patient was treated with external beam radiation, resulting in regression of the mass and resolution of the retinal detachment. CONCLUSIONS: Primary uveal lymphoma is a rare, usually indolent tumor that carries a good prognosis. In this case, we show that primary uveal lymphoma has distinct findings via histopathology and multimodal imaging, and that imaging after radiation treatment documents disease regression. PMID- 26889159 TI - Treatment of Dropped Nucleus with a 27-Gauge Twin Duty Cycle Vitreous Cutter. AB - We report herein a method for the treatment of dropped nucleus during cataract surgery with a 27-gauge twin duty cycle (TDC) vitreous cutter. When a TDC vitreous cutter is used, suction flow volume is maintained even when the cutter is driven at a high speed. This enables an Emery-Little grade 3 nucleus that had been difficult to treat with a conventional 27-gauge cutter to be successfully excised using only a vitreous cutter, with no intra- or postoperative complications. A dropped lens during cataract surgery of up to moderate hardness can be removed using a TDC cutter alone with a 27-gauge cutter system. PMID- 26889160 TI - Spontaneous Corneal Hydrops in a Patient with a Corneal Ulcer. AB - PURPOSE: We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. METHOD: This is an observational case report study. RESULTS: A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. CONCLUSION: Corneal hydrops can occur in the setting of corneal infections. PMID- 26889161 TI - Target morphology and cell memory: a model of regenerative pattern formation. AB - Despite the growing body of work on molecular components required for regenerative repair, we still lack a deep understanding of the ability of some animal species to regenerate their appropriate complex anatomical structure following damage. A key question is how regenerating systems know when to stop growth and remodeling - what mechanisms implement recognition of correct morphology that signals a stop condition? In this work, we review two conceptual models of pattern regeneration that implement a kind of pattern memory. In the first one, all cells communicate with each other and keep the value of the total signal received from the other cells. If a part of the pattern is amputated, the signal distribution changes. The difference fromthe original signal distribution stimulates cell proliferation and leads to pattern regeneration, in effect implementing an error minimization process that uses signaling memory to achieve pattern correction. In the second model, we consider a more complex pattern organization with different cell types. Each tissue contains a central (coordinator) cell that controls the tissue and communicates with the other central cells. Each of them keeps memory about the signals received from other central cells. The values of these signals depend on the mutual cell location, and the memory allows regeneration of the structure when it is modified. The purpose of these models is to suggest possible mechanisms of pattern regeneration operating on the basis of cell memory which are compatible with diverse molecular implementation mechanisms within specific organisms. PMID- 26889163 TI - Dental pulp stem cells for treating neurodegenerative diseases. PMID- 26889162 TI - Rethinking the standard trans-cortical approaches in the light of superficial white matter anatomy. AB - A better comprehension of the superficial white matter organization is important in order to minimize potential and avoidable damage to long or intermediate association fibre bundles during every step of a surgical approach. We recently proposed a technique for cadaver specimen preparation, which seems able to identify a more systematic organization of the superficial white matter terminations. Moreover, the use of the physiological intracranial vascular network for the fixation process allowed us to constantly show main vascular landmarks associated with white matter structures. Hence three examples of standard approaches to eloquent areas are herein reanalyzed starting from the first superficial layer. New insights into the possible surgical trajectories and subsequent quantitative damages of both vessels and white matter fibres can help readapt even the most standard and widely accepted approach trough the brain cortex. A more detailed study of these fine anatomical details may become in the near future a fundamental part of the neurosurgical training and the preoperative planning. PMID- 26889164 TI - Regenerative potential of targeting glycogen synthase kinase-3 signaling in neural tissues. PMID- 26889165 TI - Deriving striatal projection neurons from human pluripotent stem cells with Activin A. PMID- 26889166 TI - What can Drosophila axonal development teach us about nerve regeneration? PMID- 26889167 TI - Purinergic signalling in neuroregeneration. PMID- 26889168 TI - Platelet-rich plasma: the role in neural repair. PMID- 26889169 TI - Self-healing hydrogel for tissue repair in the central nervous system. PMID- 26889170 TI - Pharmacological inhibition of cation-chloride cotransporters for neurological diseases. PMID- 26889171 TI - All roads go to Salubrinal: endoplasmic reticulum stress, neuroprotection and glial scar formation. PMID- 26889172 TI - The inositol metabolism pathway as a target for neuroprotective strategies. PMID- 26889173 TI - Attenuation of endoplasmic reticulum stress as a treatment strategy against ischemia/reperfusion injury. PMID- 26889174 TI - Interferon beta (IFN-beta) treatment exerts potential neuroprotective effects through neurotrophic factors and novel neurotensin/neurotensin high affinity receptor 1 pathway. PMID- 26889175 TI - Releasing Nrf2 to promote neurite outgrowth. PMID- 26889176 TI - To myelinate or not to myelinate: fine tuning cAMP signaling in Schwann cells to balance cell proliferation and differentiation. PMID- 26889177 TI - Hypertonic saline: a brief overview of hemodynamic response and anti-inflammatory properties in head injury. PMID- 26889178 TI - Metabolic recruitment of spinal locomotion: intracellular neuromodulation by trace amines and their receptors. PMID- 26889179 TI - Enhanced motor cortex excitability after spinal cord injury. PMID- 26889180 TI - Dental pulp stem cells-derived schwann cells for peripheral nerve injury regeneration. PMID- 26889181 TI - N-Propionylmannosamine: using biochemical glycoengineering to promote peripheral nerve regeneration. PMID- 26889182 TI - ROCK inhibition as a novel potential strategy for axonal regeneration in optic neuropathies. PMID- 26889183 TI - The role of Islet-1 in cell specification, differentiation, and maintenance of phenotypes in the vertebrate neural retina. PMID- 26889185 TI - Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells. AB - Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls. The number of Ki-67-positive cells in rat ciliary body in the Lycium barbarum polysaccharides groups, in particular low dose Lycium barbarum polysaccharides group, was significantly greater than that in the phosphate buffered saline group. Ki-67-positive rat ciliary body cells expressed nestin but they did not express glial fibrillary acidic protein. These findings suggest that Lycium barbarum polysaccharides can promote the proliferation of adult rat retinal progenitor cells and the proliferated cells present with neuronal phenotype. PMID- 26889184 TI - Repair, protection and regeneration of spinal cord injury. PMID- 26889187 TI - Correction: Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target? AB - [This corrects the article on p. 244 in vol. 10, PMID: 25883623.]. PMID- 26889186 TI - Exogenous nerve growth factor protects the hypoglossal nerve against crush injury. AB - Studies have shown that sensory nerve damage can activate the p38 mitogen activated protein kinase (MAPK) pathway, but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear. Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury, but there has been little research focusing on the hypoglossal nerve injury and repair. In this study, we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days. p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury; exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus. Under transmission electron microscopy, we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury. Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury. PMID- 26889188 TI - Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involve the nuclear erythroid 2-related factor 2 pathway. AB - Salidroside, the main active ingredient extracted from Rhodiola crenulata, has been shown to be neuroprotective in ischemic cerebral injury, but the underlying mechanism for this neuroprotection is poorly understood. In the current study, the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was investigated in a rat model of middle cerebral artery occlusion. Salidroside (30 mg/kg) reduced infarct size, improved neurological function and histological changes, increased activity of superoxide dismutase and glutathione S-transferase, and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion. Furthermore, salidroside apparently increased Nrf2 and heme oxygenase-1 expression. These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved. The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke. PMID- 26889189 TI - Acupuncture for ischemic stroke: cerebellar activation may be a central mechanism following Deqi. AB - The needling sensation of Deqi during acupuncture is a key factor of influencing acupuncture outcome. Recent studies have mainly focused on the brain function effects of Deqi in a physiological state. Functional magnetic resonance imaging (fMRI) on the effects of acupuncture at Waiguan (SJ5) in pathological and physiological states is controversial. In this study, 12 patients with ischemic stroke received acupuncture at Waiguan (SJ5) and simultaneously underwent fMRI scanning of the brain, with imaging data of the activated areas obtained. Based on the patient's sensation, imaging data were allocated to either the Deqi group or non-Deqi group. In the Deqi group, the activated/deactivated areas were the left superior temporal gyrus (BA39)/right anterior lobe of the cerebellum and left thalamus. In the non-Deqi group, the activated areas included the medial frontal gyrus of the right frontal lobe (BA11), right limbic lobe (BA30, 35), and left frontal lobe (BA47), while the only deactivated area was the right parietal lobe (BA40). Compared with the non-Deqi group, the Deqi group exhibited marked activation of the right anterior lobe of the cerebellum and right limbic lobe (BA30). These findings confirm that the clinical effect of Deqi during acupuncture is based on brain functional changes. Cerebellar activation may be one of the central mechanisms of acupuncture in the treatment of ischemic stroke. PMID- 26889190 TI - Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats. AB - Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT) involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of 'learned non-use' and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model) group, a CIMT + model (CIMT) group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi. PMID- 26889192 TI - Correction: Curcumin and Apigenin - novel and promising therapeutics against chronic neuroinflammation in Alzheimer's disease. AB - [This corrects the article on p. 1181 in vol. 10, PMID: 26487830.]. PMID- 26889191 TI - In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells. AB - Drugs for the treatment and prevention of nervous system diseases must permeate the blood-brain barrier to take effect. In vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation mechanisms. However, to date, no unified method has been described for establishing a blood-brain barrier model. Here, we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-um pores, and conducted transepithelial electrical resistance measurements, leakage tests and assays for specific blood-brain barrier enzymes. We show that the permeability of our model is as low as that of the blood-brain barrier in vivo. Our model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs. PMID- 26889193 TI - Mononuclear cells from the cord blood and granulocytecolony stimulating factor mobilized peripheral blood: is there a potential for treatment of cerebral palsy? AB - To investigate a possible therapeutic mechanism of cell therapy in the field of cerebral palsy using granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (mPBMCs), we compared the expression of inflammatory cytokines and neurotrophic factors in PBMCs and mPBMCs from children with cerebral palsy to those from healthy adult donors and to cord blood mononuclear cells donated from healthy newborns. No significant differences in expression of neurotrophic factors were found between PBMCs and mPBMCs. However, in cerebral palsy children, the expression of interleukin-6 was significantly increased in mPBMCs as compared to PBMCs, and the expression of interleukin-3 was significantly decreased in mPBMCs as compared to PBMCs. In healthy adults, the expression levels of both interleukin-1beta and interleukin-6 were significantly increased in mPBMCs as compared to PBMCs. The expression of brain-derived neurotrophic factors in mPBMC from cerebral palsy children was significantly higher than that in the cord blood or mPBMCs from healthy adults. The expression of G-CSF in mPBMCs from cerebral palsy children was comparable to that in the cord blood but significantly higher than that in mPBMCs from healthy adults. Lower expression of pro-inflammatory cytokines (interleukin-1beta, interleukin-3, and -6) and higher expression of anti-inflammatory cytokines (interleukin-8 and interleukin-9) were observed from the cord blood and mPBMCs from cerebral palsy children rather than from healthy adults. These findings indicate that mPBMCs from cerebral palsy and cord blood mononuclear cells from healthy newborns have the potential to become seed cells for treatment of cerebral palsy. PMID- 26889194 TI - A novel method for evaluating brain function and microstructural changes in Parkinson's disease. AB - In this study, microstructural brain damage in Parkinson's disease patients was examined using diffusion tensor imaging and tract-based spatial statistics. The analyses revealed the presence of neuronal damage in the substantia nigra and putamen in the Parkinson's disease patients. Moreover, disease symptoms worsened with increasing damage to the substantia nigra, confirming that the substantia nigra and basal ganglia are the main structures affected in Parkinson's disease. We also found that microstructural damage to the putamen, caudate nucleus and frontal lobe positively correlated with depression. Based on the tract-based spatial statistics, various white matter tracts appeared to have microstructural damage, and this correlated with cognitive disorder and depression. Taken together, our results suggest that diffusion tensor imaging and tract-based spatial statistics can be used to effectively study brain function and microstructural changes in patients with Parkinson's disease. Our novel findings should contribute to our understanding of the histopathological basis of cognitive dysfunction and depression in Parkinson's disease. PMID- 26889196 TI - Transplantation of human telomerase reverse transcriptase gene-transfected Schwann cells for repairing spinal cord injury. AB - Transfection of the human telomerase reverse transcriptase (hTERT) gene has been shown to increase cell proliferation and enhance tissue repair. In the present study, hTERT was transfected into rat Schwann cells. A rat model of acute spinal cord injury was established by the modified free-falling method. Retrovirus PLXSN was injected at the site of spinal cord injury as a vector to mediate hTERT gene transfected Schwann cells (1 * 10(10)/L; 10 MUL) or Schwann cells (1 * 10(10)/L; 10 MUL) without hTERT gene transfection. Between 1 and 4 weeks after model establishment, motor function of the lower limb improved in the hTERT-transfected group compared with the group with non-transfected Schwann cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and reverse transcription-polymerase chain reaction results revealed that the number of apoptotic cells, and gene expression of aquaporin 4/9 and matrix metalloproteinase 9/2 decreased at the site of injury in both groups; however, the effect improved in the hTERT-transfected group compared with the Schwann cells without hTERT transfection group. Hematoxylin and eosin staining, PKH26 fluorescent labeling, and electrophysiological testing demonstrated that compared with the non-transfected group, spinal cord cavity and motor and sensory evoked potential latencies were reduced, while the number of PKH26-positive cells and the motor and sensory evoked potential amplitude increased at the site of injury in the hTERT-transfected group. These findings suggest that transplantation of hTERT gene-transfected Schwann cells repairs the structure and function of the injured spinal cord. PMID- 26889195 TI - Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord. AB - Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury. However, the mechanism of action remains unclear. In this study, a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method. Twenty-four hours after injury, Zusanli (ST36), Xuanzhong (GB39), Futu (ST32) and Sanyinjiao (SP6) were stimulated with electroacupuncture. Rats with spinal cord injury alone were used as controls. At 2, 4 and 6 weeks after injury, acetylcholinesterase (AChE) activity at the site of injury, the number of medium and large neurons in the spinal cord anterior horn, glial cell line-derived neurotrophic factor (GDNF) mRNA expression, and Basso, Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group. These results demonstrate that electroacupuncture increases AChE activity, up regulates GDNF mRNA expression, and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury. PMID- 26889197 TI - Polyurethane/poly(vinyl alcohol) hydrogel coating improves the cytocompatibility of neural electrodes. AB - Neural electrodes, the core component of neural prostheses, are usually encapsulated in polydimethylsiloxane (PDMS). However, PDMS can generate a tissue response after implantation. Based on the physicochemical properties and excellent biocompatibility of polyurethane (PU) and poly(vinyl alcohol) (PVA) when used as coating materials, we synthesized PU/PVA hydrogel coatings and coated the surface of PDMS using plasma treatment, and the cytocompatibility to rat pheochromocytoma (PC12) cells was assessed. Protein adsorption tests indicated that the amount of protein adsorption onto the PDMS substrate was reduced by 92% after coating with the hydrogel. Moreover, the PC12 cells on the PU/PVA-coated PDMS showed higher cell density and longer and more numerous neurites than those on the uncoated PDMS. These results indicate that the PU/PVA hydrogel is cytocompatible and a promising coating material for neural electrodes to improve their biocompatibility. PMID- 26889199 TI - Neglected corticospinal tract injury for 10 months in a stroke patient. PMID- 26889198 TI - Activation of less affected corticospinal tract and poor motor outcome in hemiplegic pediatric patients: a diffusion tensor tractography imaging study. AB - The less affected hemisphere is important in motor recovery in mature brains. However, in terms of motor outcome in immature brains, no study has been reported on the less affected corticospinal tract in hemiplegic pediatric patients. Therefore, we examined the relationship between the condition of the less affected corticospinal tract and motor function in hemiplegic pediatric patients. Forty patients with hemiplegia due to perinatal or prenatal injury (13.7 +/- 3.0 months) and 40 age-matched typically developing controls were recruited. These patients were divided into two age-matched groups, the high functioning group (20 patients) and the low functioning group (20 patients) using functional level of hemiplegia scale. Diffusion tensor tractography images showed that compared with the control group, the patient group of the less affected corticospinal tract showed significantly increased fiber number and significantly decreased fractional anisotropy value. Significantly increased fiber number and significantly decreased fractional anisotropy value in the low functioning group were observed than in the high functioning group. These findings suggest that activation of the less affected hemisphere presenting as increased fiber number and decreased fractional anisotropy value is related to poor motor function in pediatric hemiplegic patients. PMID- 26889201 TI - Correction: Gene therapy in Parkinson's disease: targeting the endoplasmic reticulum proteostasis network. AB - [This corrects the article on p. 1053 in vol. 10, PMID: 26330821.]. PMID- 26889200 TI - Structural and functional connectivity in traumatic brain injury. AB - Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID- 26889203 TI - Assessing the sensitivity and specificity of First Response HIV-1-2 test kit with whole blood and serum samples: a cross-sectional study. AB - BACKGROUND: Human immunodeficiency virus (HIV) Rapid diagnostic Test (RDT) kits are the preferred assays for HIV testing in many countries. Prevention of Mother to-Child Transmission, Know Your Status Campaigns, Blood-Safety, Voluntary Counseling and Testing are major strategies adapted to control transmission of the virus and the pivot of these interventions is either screening or diagnosing individuals through testing. There are reports of inconsistent sensitivity and specificity with whole blood and serum samples collected from the same individual. Little is known about the diagnostic characteristics of First Response HIV-1-2 RDT kit, used as a single test kit in national HIV prevention and control programmes. The debate has always centered on choosing between whole blood and serum in a case where a single test kit that runs on only blood specimen will be used for testing. The variations in specificities and sensitivities with whole blood and serum samples imply that some individuals who might be true positives will be missed and elude care. This study determined the best blood-based specimen type (whole blood or serum) that improves performance of First Response HIV RDT kit in detecting HIV-specific antibodies. METHODS: A hospital-based cross-sectional study was conducted on 280 HIV infected and non infected patients from May 2015 to June 2015. Blood samples from each participant were separated into whole blood and serum, and tested on First Response HIV-1-2 kits (Premier Medical Corporation Ltd., Kachigam, India) using Electro-chemi luminescence assay (ECLIA) as reference assay. RESULTS: First Response HIV-1-2 RDT kit showed 100 % sensitivity and 100 % specificity with whole blood specimen and 100 % sensitivity and 82.86 % specificity with serum specimen for the detection of HIV-1. The positive and negative predictive values were 100, 100 and 85.35, 82.86 % for whole blood and serum respectively. CONCLUSION: Whole blood specimen(s) from an individual have higher specificity, positive and negative predictive values than serum. Whole blood is the primary specimen to use on First Response HIV-1-2 RDT kit when screening peripheral blood for HIV-1-specific antibodies. PMID- 26889202 TI - Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation. AB - Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques. PMID- 26889204 TI - Rate of initial highly active anti-retroviral therapy regimen change and its predictors among adult HIV patients at University of Gondar Referral Hospital, Northwest Ethiopia: a retrospective follow up study. AB - BACKGROUND: Regimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. In a resource limited setting where treatment options are limited, designing strategies to increase the durability of original regimen are essential. However, information's on rate of initial regimen change and its predictors is scarce in Ethiopia. Therefore, the purpose of this study was to assess the rate of initial highly active anti retroviral therapy (HAART) regimen change and its predictors among adult HIV patients at the University of Gondar Referral Hospital, Northwest Ethiopia. METHODS: An institutional based retrospective follow up study was conducted among 410 adult HIV patients started HAART from January 2010 to December 2014. Simple random sampling technique was used to select patient records using computer generated random number. Data were collected from patient chart using data extraction tool. The Kaplan-Meier curve was used to estimate the median duration of regimen change. Life table was used to estimate the cumulative survival for initial regimen change and log rank test to compare regimen change survival curves between the different categories of explanatory variables. Bivariate and multivariate Cox proportional hazard model were used to identify predictors of initial regimen change. RESULTS: The overall incidence rate of initial regimen change was 10.11 (95 % CI 8.29, 12.6) per 100 person years (PY). Baseline WHO clinical stage III (AHR = 1.92, 95 % CI 1.12-3.35), occurrence of tuberculosis (TB) on the initial regimen (AHR = 8.33, 95 % CI 4.47-15.53), side effect on the initial regimen (AHR = 25.27, 95 % CI 15.12-42.00) and co-medication with ART (AHR = 2.5, 95 % CI 1.46-4.34) were significant predictors of initial regimen change. CONCLUSIONS: The rate of initial HAART regimen change was found to be high. Having WHO clinical stage III, co-medication with ART, occurrence of tuberculosis and side effect on initial regimen were independent predictors of regimen change. Hence, close follow-up and screening of patient for side effect and tuberculosis is important. PMID- 26889205 TI - Simultaneous knockdown of six non-family genes using a single synthetic RNAi fragment in Arabidopsis thaliana. AB - BACKGROUND: Genetic engineering of plants that results in successful establishment of new biochemical or regulatory pathways requires stable introduction of one or more genes into the plant genome. It might also be necessary to down-regulate or turn off expression of endogenous genes in order to reduce activity of competing pathways. An established way to knockdown gene expression in plants is expressing a hairpin-RNAi construct, eventually leading to degradation of a specifically targeted mRNA. Knockdown of multiple genes that do not share homologous sequences is still challenging and involves either sophisticated cloning strategies to create vectors with different serial expression constructs or multiple transformation events that is often restricted by a lack of available transformation markers. RESULTS: Synthetic RNAi fragments were assembled in yeast carrying homologous sequences to six or seven non-family genes and introduced into pAGRIKOLA. Transformation of Arabidopsis thaliana and subsequent expression analysis of targeted genes proved efficient knockdown of all target genes. CONCLUSIONS: We present a simple and cost-effective method to create constructs to simultaneously knockdown multiple non-family genes or genes that do not share sequence homology. The presented method can be applied in plant and animal synthetic biology as well as traditional plant and animal genetic engineering. PMID- 26889206 TI - Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test. AB - BACKGROUND: The association of human papillomavirus (HPV) with cervical cancer is well established. AIM: To investigate HPV genotype distribution and co-infection occurrence in cervical specimens from a group of Egyptian women. METHODS: A group of 152 women with and without cervical lesions were studied. All women had cervical cytology and HPV testing. They were classified according to cytology into those with normal cytology, with squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma (SCC). Cervical samples were analyzed to identify the presence of HPV by PCR, and all positive HPV-DNA samples underwent viral genotype analysis by means of LINEAR ARRAY HPV Genotyping assay. RESULTS: A total of 26 HPV types with a prevalence of 40.8 % were detected. This prevalence was distributed as follows: 17.7 % among cytologically normal females, 56.5, 3.2, and 22.6 % among those with LSIL, HSIL and invasive SCC respectively. Low-risk HPV types were detected in 81.8 % of the cytologically-normal women, in 5.7 % of those in LSIL women, and in 14.3 % of infections with invasive SCC, while no low risk types were detected in HSIL. High-risk HPV types were detected in 18.2 % of infections in the cytologically normal women, 14.3 % of infections in LSIL, and in 21.4 % of invasive lesions. The probable and possible carcinogenic HPV were not detected as single infections. Mixed infection was present in 80 % of women with LSIL, in 100 % of those with HSIL, and in 64.3 % of those with invasive SCC. This difference was statistically significant. HPV 16, 18 and 31 were the most prevalent HR HPV types, constituting 41.9, 29.03 and 12.9 % respectively, and HPV 6, 62 and CP6108 were the most prevalent LR HPV types constituting 11.3, 9.7 and 9.7 % respectively. CONCLUSION: These data expand the knowledge concerning HPV prevalence and type distribution in Egypt which may help to create a national HPV prevention program. HPV testing using the LINEAR ARRAY HPV Genotyping assay is a useful tool when combined with cytology in the diagnosis of mixed and non conventional HPV viral types. PMID- 26889207 TI - Profiling placental and fetal DNA methylation in human neural tube defects. AB - BACKGROUND: The incidence of neural tube defects (NTDs) declined by about 40 % in Canada with the introduction of a national folic acid (FA) fortification program. Despite the fact that few Canadians currently exhibit folate deficiency, NTDs are still the second most common congenital abnormality. FA fortification may have aided in reducing the incidence of NTDs by overcoming abnormal one carbon metabolism cycling, the process which provides one carbon units for methylation of DNA. We considered that NTDs persisting in a folate-replete population may also occur in the context of FA-independent compromised one carbon metabolism, and that this might manifest as abnormal DNA methylation (DNAm). Second trimester human placental chorionic villi, kidney, spinal cord, brain, and muscle were collected from 19 control, 22 spina bifida, and 15 anencephalic fetuses in British Columbia, Canada. DNA was extracted, assessed for methylenetetrahydrofolate reductase (MTHFR) genotype and for genome-wide DNAm using repetitive elements, in addition to the Illumina Infinium HumanMethylation450 (450k) array. RESULTS: No difference in repetitive element DNAm was noted between NTD status groups. Using a false discovery rate <0.05 and average group difference in DNAm >=0.05, differentially methylated array sites were identified only in (1) the comparison of anencephaly to controls in chorionic villi (n = 4 sites) and (2) the comparison of spina bifida to controls in kidney (n = 3342 sites). CONCLUSIONS: We suggest that the distinctive DNAm of spina bifida kidneys may be consequent to the neural tube defect or reflective of a common etiology for abnormal neural tube and renal development. Though there were some small shifts in DNAm in the other tested tissues, our data do not support the long-standing hypothesis of generalized altered genome-wide DNAm in NTDs. This finding may be related to the fact that most Canadians are not folate deficient, but it importantly opens the field to the investigation of other epigenetic and non-epigenetic mechanisms in the etiology of NTDs. PMID- 26889209 TI - Effects of different exercise programs and minimal detectable changes in hemoglobin A1c in patients with type 2 diabetes. AB - BACKGROUND: The incidence of diabetes mellitus is increasing worldwide, resulting in a global epidemic. The most common type, the type 2 diabetes mellitus, constitutes of 90-95 % of the cases and is characterized by the action of and/or impaired insulin secretion. Regular exercise is a recommended strategy in several studies and guidelines for type 2 diabetes control and complications associated with it. Therefore, we evaluated and compared the effects of aerobic and strength exercise programs on the glycemic control in patients with type 2 diabetes. METHODS: The selected patients were divided into groups which performed moderate strength training (ST) and aerobic training (AT). The study lasted 20 weeks and was divided into two 10 week phases with anthropometric (body mass index, waist, abdomen and hips circumferences, waist/hip ratio) and biochemical (glycemic and lipid profile) assessments at baseline, 10 weeks and 20 weeks. For intra and inter analyses a mixed ANOVA model was used. Individual changes were calculated using the minimum detectable change, based on a 90 % confidence interval. RESULTS: Eleven patients (five men and six women) completed the 20 weeks of training; five from the ST group and six from the AT. No significant changes were observed in any anthropometric variable in either group. Statistically significant differences were found in mean hemoglobin A1c in both groups between baseline (AT: 8.6 +/- 2.5; ST: 9.2 +/- 1.9) and 10 weeks (AT: 7.2 +/- 1.7; ST: 7.9 +/- 1.2) (p = 0.03), and baseline (AT: 8.6 +/- 2.5; ST: 9.2 +/- 1.9) and 20 weeks (AT: 7.5 +/- 1.7; ST: 7.4 +/- 0.9) (p = 0.01). For the minimal detectable changes, 40 % of the ST and 33 % of AT achieved these changes for hemoglobin A1c. CONCLUSION: Both aerobic and strength exercises can help the metabolic control in patients with type 2 diabetes, even without significant changes in anthropometry over the 20 weeks of training. However, this period was sufficient to cause changes in hemoglobin A1c values and the estimated average glucose, which are important parameters in controlling diabetes, thus signaling an important consequence of adhering to an exercise routine for type 2 diabetic patients. PMID- 26889208 TI - Oestrogen receptor beta regulates epigenetic patterns at specific genomic loci through interaction with thymine DNA glycosylase. AB - BACKGROUND: DNA methylation is one way to encode epigenetic information and plays a crucial role in regulating gene expression during embryonic development. DNA methylation marks are established by the DNA methyltransferases and, recently, a mechanism for active DNA demethylation has emerged involving the ten-eleven translocator proteins and thymine DNA glycosylase (TDG). However, so far it is not clear how these enzymes are recruited to, and regulate DNA methylation at, specific genomic loci. A number of studies imply that sequence-specific transcription factors are involved in targeting DNA methylation and demethylation processes. Oestrogen receptor beta (ERbeta) is a ligand-inducible transcription factor regulating gene expression in response to the female sex hormone oestrogen. Previously, we found that ERbeta deficiency results in changes in DNA methylation patterns at two gene promoters, implicating an involvement of ERbeta in DNA methylation. In this study, we set out to explore this involvement on a genome-wide level, and to investigate the underlying mechanisms of this function. RESULTS: Using reduced representation bisulfite sequencing, we compared genome wide DNA methylation in mouse embryonic fibroblasts derived from wildtype and ERbeta knock-out mice, and identified around 8000 differentially methylated positions (DMPs). Validation and further characterisation of selected DMPs showed that differences in methylation correlated with changes in expression of the nearest gene. Additionally, re-introduction of ERbeta into the knock-out cells could reverse hypermethylation and reactivate expression of some of the genes. We also show that ERbeta is recruited to regions around hypermethylated DMPs. Finally, we demonstrate here that ERbeta interacts with TDG and that TDG binds ERbeta-dependently to hypermethylated DMPs. CONCLUSION: We provide evidence that ERbeta plays a role in regulating DNA methylation at specific genomic loci, likely as the result of its interaction with TDG at these regions. Our findings imply a novel function of ERbeta, beyond direct transcriptional control, in regulating DNA methylation at target genes. Further, they shed light on the question how DNA methylation is regulated at specific genomic loci by supporting a concept in which sequence-specific transcription factors can target factors that regulate DNA methylation patterns. PMID- 26889210 TI - Paediatric Virology: A new paediatric subspecialty? A proposal at the Workshop on Paediatric Virology, Athens, October 10, 2015. PMID- 26889212 TI - Fluoro-edenite and carbon nanotubes: The health impact of 'asbestos-like' fibres. AB - Several decades have passed since Wagner et al demonstrated a causal link between asbestos fibre inhalation and the development of pleural mesothelioma in 1960. It was later suggested that pleural plaques are a benign consequence of exposure to these fibres. Most recently, a significant association between exposure to asbestos and cancer diagnosed at various sites, such as the peritoneum, stomach, pharynx, colon and ovaries has been demonstrated. The great concerns about public health that arose from the scientific evidence presented above have led to the banning of asbestos in several countries. Over the years, the suspicion that particles with a high aspect ratio may have asbestos-like pathogenicity has been supported by increasing evidence. Natural occurring minerals, as well as man-made fibres, have proven capable of inducing either chronic inflammation of serous membranes, or, in some cases, the development of peritoneal and pleural mesothelioma. The pathogenic role of both fluoro-edenite and carbon nanotubes, two 'asbestos-like' fibres is summarized and discussed in this review. The data presented herein support the notion that occupational exposure to these two types of fibre contributes to the development of different types of cancer. PMID- 26889213 TI - Association of Notch3 single-nucleotide polymorphisms and lacunar infarctions in patients. AB - Cerebrovascular disease is a leading cause of morbidity and mortality worldwide, which is influenced by genetic and environmental factors. The aim of the present study was to examine the association between single-nucleotide polymorphisms (SNPs) in Notch3 exons 3-6 and lacunar infarction by comparing SNPs between control subjects and those with lacunar infarction. A single-center case-control study was conducted to investigate the association between Notch3 SNPs and risk of stroke. A total of 140 patients were included in the study, 30 of whom had no infarction (control) and 110 had lacunar infarction. Lacunar patients were divided into the 'pure lacunar' and 'lacunar + leukoarasis' groups based on brain imaging. All the patients were of Chinese Han ethnicity, and the male to female ratio was 84:56. Patient clinical histories included hypertension, diabetes mellitus (DM), hyperlipidemia, and heart disease were recorded. The Notch3 sequence was obtained from the National Centser for Biotechnology Information database. Notch3 was amplified by polymerase chain reaction from whole blood samples, and exons 3-6 were sequenced to identify SNPs. The result showed that there was no significant difference in the prevalence of hypertension, DM, hyperlipidemia, and heart disease between the control and lacunar infarction patients. Notabley, the age of the lacunar + leukoarasis patients was significantly higher than that of the control and pure lacunar patients (P<0.05). Eight SNPs were detected at low frequencies, and only rs3815388 and rs1043994 exhibited slightly higher frequencies. A chi2 test indicated that Notch3 SNPs, particularly rs1043994, were associated with lacunar infarction (P<0.05). In conclusion, the result of the present study have shown that Notch3 SNPs, particularly rs1043994, are associated with lacunar infarction. PMID- 26889211 TI - Current views and advances on Paediatric Virology: An update for paediatric trainees. AB - Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop. PMID- 26889214 TI - Effect of cold stress on immunity in rats. AB - An increase in the morbidity of upper respiratory tract infections and the attack and exacerbation of autoimmune diseases has been observed to occur in the few days following sudden environmental temperature decreases, but the mechanisms for these phenomena are not well understood. To determine the effect of a sudden ambient temperature drop on the levels of stress hormones and T-lymphocyte cytokines in the plasma, the Toll-like receptor 4 (TLR4) expression of immunocompetent cells in rat spleens and the levels of regulatory T (Treg) cells in the peripheral blood, Sprague Dawley rats were divided into three groups of different ambient temperatures (20, 4 and -12 degrees C). In each group, there were four observation time-points (1, 12, 24 and 48 h). Each ambient temperature group was subdivided into non-stimulation, lipopolysaccharide-stimulation and concanavalin A-stimulation groups. The levels of adrenocorticotropin (ACTH), epinephrine (EPI), angiotensin-II (ANG-II), interleukin-2 (IL-2), interferon gamma (IFN-gamma), IL-4 and IL-10 in the plasma were determined using ELISA. The cellular expression levels of TLR4 and the presence of cluster of differentiation (CD)4+CD25+ and CD4+CD25+Forkhead box P3 (Foxp3)+ cells were determined using flow cytometry. The experiments demonstrated that the ACTH, EPI, ANG-II and IL-10 levels in the plasma were significantly increased at 4 and -12 degrees C compared with those at 20 degrees C, while the plasma levels of IFN-gamma, IL-2 and IL-4, the TLR4 expression rates of immunocompetent cells in the rat spleen and the percentage of CD4+CD25+Foxp3+ Treg cells among the CD4+CD25+ Treg cells in the peripheral blood were decreased at 4 and -12 degrees C compared with those at 20 degrees C. These data indicate that cold stress affects the stress hormones and the innate and adaptive immunity functions in rats. PMID- 26889216 TI - Immunosuppressive agents versus steroids in the treatment of IgA nephropathy induced proteinuria: A meta-analysis. AB - Immunoglobulin A nephropathy (IgAN) is one of the most common types of primary glomerular disease. Immunosuppressive treatment for patients with IgAN remains controversial. The present meta-analysis aimed to assess the efficacy and safety of various immunosuppressive agents compared with steroids in patients with IgAN and moderate to severe proteinuria. PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Weipu, Chinese Biomedical Literature Database and Qinghuatongfang were searched for relevant randomized controlled trials (RCTs) published between 1990 and September 2013. All eligible studies (biopsy proven IgA nephropathy, use of immunosuppressive agents) measured urinary protein excretion and proteinuria remission. Data were analyzed with the random effects model using Review Manager. A total of 29 RCTs were included, involving 1,466 patients. Compared with steroids, immunosuppressive agents, including acetazolamide (AZA) [complete response (CR)/partial response (PR); relative risk (RR), 3.43; 95% confidence interval (CI) 1.92-6.12; P<0.0001], mycophenolate mofetil (MMF) (CR/PR; RR, 2.19; 95% CI, 1.25-3.85; P=0.006) and leflunomide (LET) (CR/PR; RR, 2.64; 95% CI, 1.80-3.86; P<0.00001) resulted in increased partial or complete proteinuria remission. Cyclophosphamide (CTX) resulted in a higher reduction of urinary protein excretion than steroids (SMD, 0.91; 95% CI, 0.41 1.41; P=0.0004)). Compared to CTX, LET showed higher effectiveness (CR/PR; RR, 2.01; 95% CI, 1.08-3.75; P=0.03) with a lower incidence of adverse events. The present meta-analysis, which is based on IgAN patients, suggested that AZA, MMF, LET and CTX are effective in reducing proteinuria levels, with acceptable side effects. Therefore, immunosuppressive agents may be considered promising therapeutic agents for the treatment of IgAN and should be investigated further in large sample size, high-quality studies. PMID- 26889215 TI - Analysis of the clinical value of 18F-FDG PET/CT in hepatic alveolar echinococcosis before and after autologous liver transplantation. AB - The aim of this study was to evaluate the clinical value of 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in advanced liver alveolar echinococcosis (LAE) prior to and following autologous liver transplantation (ALT). The biodistribution of lesions in 8 patients was recorded using 18F-FDG PET/CT prior to and following surgery. The maximum standardized uptake value (SUVmax) of the lesions was also measured and compared with the pathological results. The overall hepatic peri-lesion SUVmax of the patients was 3.57+/-1.21, and the delayed SUVmax was 4.19+/-1.70. The diagnostic sensitivity of 18F-FDG PET/CT in LAE was 91.67%, with a specificity of 60.00% and accuracy of 82.35%. The positive predictive value was 84.62%, and the negative predictive value was 75.00%. SUVmax values of the surviving liver were 1.23+/-0.78 after 1 month, 1.15+/-0.67 after 3 months and 0.85+/-0.35 after 6 months. Compared with normal liver values (0.95+/-0.19), the 1-month SUVmax was significantly different. The SUVmax in 3 patients with high-lividity lesions was 2.05+/-0.72, and the delayed SUVmax was 3.15+/-0.83; 3 months after transplantation, the SUVmax was 1.85+/-0.62, and the delayed SUVmax was 2.95+/ 0.79, revealing no significant difference. In conclusion, 18F-FDG PET/CT is effective for determining the biological boundary of LAE and shows important clinical value in determining the metabolic activities of the surviving liver following ALT. PMID- 26889217 TI - Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction. AB - Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID- 26889218 TI - Laryngeal mask airway without muscle relaxant in femoral head replacement in elderly patients. AB - The number of elderly patients undergoing femoral head replacement surgeries is on the increase. These patients often suffer from comorbidity such as cardiovascular and cerebrovascular complications, which limits the ability of medical teams to employ anesthesia. Thus, alternative methods are required. The aim of this study was to examine the advantage of laryngeal mask airway (LMA) in the absence of muscle relaxant in elderly patients undergoing femoral head replacement operations. Fifty patients (27 males and 23 females) undergoing femoral head replacements were selected for the study between March 2013 and May 2014. The mean value for the age in this group was 74.6+/-12.5 years. The patients were randomly distributed into two groups of 25. One group was designated as the treatment group and the second group as the control group. For the treatment group, LMA without muscle relaxant was used, and the control group received routine anesthesia. Variations in heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SPO2) in the two groups were monitored at different times. Clinical efficacy and muscle relaxation effects were also analyzed. For the treatment group, the HR, MAP and SPO2 measurements did not reveal any significant variation while these values in the control group demonstrated important dissimilarities. Time to recovery, time to extubation and incidence of throat pain in the treatment group were all markedly decreased as compared to those in control group. The operation time in the treatment group was not significantly different to that of control group. The satisfaction of the muscle relaxation effect in the treatment group was significantly higher than that in the control group while the incidence of adverse reactions was not considerably different. In conclusion, the use of LMA without using muscle relaxant in femoral head replacement surgeries performed on elderly patients showed to be effective and safe. PMID- 26889219 TI - Pterygium concomitant with other ocular surface lesions: Clinical implications and pathogenetic links. AB - In the present study, we aimed to evaluate the co-existence of ophthalmic pterygium with other ocular surface lesions in a cohort of patients from the Cretan population. This is a retrospective evaluation of all pterygia in patients examined and treated at the Department of Ophthalmology of the University Hospital of Heraklion, Greece during an 8-year period (from June 2006 to June 2014). A total of 158 cases was examined. Ocular surface images and medical history were evaluated in order to detect concomitant ocular surface pathological conditions. Concomitant lesions included conjunctival nevi (5 cases, 3.16%), iris nevi (4 cases, 2.53%), conjunctival papillomas (8 cases, 5.06%), conjunctival intraepithelial neoplasia (CIN; 4 cases, 2.53%) and 6 cases of hypertophy of the plica semilunaris (3.79%). Of note, pterygium was overlying the iris which was occupied by the iris nevus in 2 out of the 4 cases of iris nevus. Overall, our data indicate that ophthalmic pterygium may often co-exist with other clinically significant ocular surface lesions. The association of ophthalmic pterygium with conjunctival papillomas or CIN stresses the potential involvement of human papilloma virus in the pathogenesis of ophthalmic pterygium, whereas the topographical association of pterygium with iris nevus may offer support to the transcameral light pathway pathogenetic mechanism. PMID- 26889220 TI - Hepcidin in non-alcoholic fatty liver disease regulated by the TLR4/NF-kappaB signaling pathway. AB - The aim of our study was to analyze the role of toll-like receptor 4 (TLR4)/nuclear factor (NF)-kappaB signal pathway on Hepcidin regulation in non alcoholic fatty liver disease (NAFLD). A total of 60 male Sprague-Dawley rats were randomly divided into the control, NAFLD and intervention groups. Rats in the control group were fed with standard laboratory diet, and rats in the NAFLD and intervention groups were fed with a high-fat diet. A final volume of 2 ml of pathenolide (10 umol/l) was administered intraperitoneally only to the rats in the intervention group. The tissue sections were stained with hematoxylin and eosin and the pathological changes in liver tissues were observed and scored. The levels of TLR4 and NF-kappaB in liver tissues were quantified by western blotting. NAFLD rats appeared to have typical liver fatty degeneration and the expression of TLR4/NF-kappaB proteins and Hepcidin mRNA was significantly higher than that in the control group (P<0.05). However, the pathological changes observed in the intervention group had a marked improvement with a significant reduction in the TLR4/NF-kappaB protein and Hepcidin mRNA expression (P<0.05). In conclusion, the abnormal activation of the TLR4/NF-kappaB signaling pathway may cause NAFLD through the overexpression of Hepcidin. PMID- 26889221 TI - High-frequency ultrasound as an adjunct to neural electrophysiology: Evaluation and prognosis of Bell's palsy. AB - Bell's palsy is a form of temporary facial nerve paralysis that occurs primarily in young adults. Previously, various methods were used to assess outcomes in facial nerve disease. The aim of the present study was to characterize the main branches of the normal and abnormal facial nerve using high-frequency ultrasonography (HFUS). A total of 104 healthy volunteers, 40 patients with acute onset of Bell's palsy and 30 patients who underwent 3-month routine therapy for Bell's palsy disease were included in the study. The healthy volunteers and patients were selected for HFUS examination and VII nerve conduction. The results showed significant differences in nerve diameter, echogenicity, delitescence and amplitude in different groups. Statistically significant correlations were identified for severity grading in one of the experimental groups during HFUS examinations. In conclusion, HFUS as a complementary technique paired with neural electrophysiology may establish the normal values of facial nerve. Additionally, HFUS was beneficial in the process of evaluation and prognosis of Bell's palsy disease. PMID- 26889222 TI - Early prediction of death in acute hypertensive intracerebral hemorrhage. AB - Hypertensive intracerebral hemorrhage (HICH) has been on the decline. However, mortality at long-term follow up is on the increase. The aim of the present study was to investigate early warning signals of death in patients with acute HICH. The medical records of 128 patients with acute HICH within 6 h of onset were retrospectively analyzed. For these patients, systolic blood pressure (BP) was recorded at different time points (emergency, admission, every 6 h within 24 h and twice daily after 24 h) within 1 week. Computed tomography scanning was performed at emergency and the following 24+/-3 h to assess the hematoma volume. Neurological impairment was evaluated using the Glasgow Coma Scale and National Institutes of Health Stroke Scale. Outcomes were death, defined as a modified Rankin scale score 6, at 90 days. The results showed that at 90 days, 15 HICH patients succumbed (mortality of 11.7%). Of the 15 patients, 1 patient (6.7%) sucumbed within 24 h and 6 patients (40%) within 1 week. HICH mortality was closely associated with age (P<0.001) but not with gender. A significant association was detected between mortality and high BP taken at 30 min, 45 min and 6 h after admission (P=0.003), albeit not at emergency and admission (P>0.05). Death was also correlated with hematoma volume at 24 h but not with the site. Results from the multivariate binary logistic regression analysis showed that age and hematoma volume were independent risk factors of death of HICH. In conclusion, age and hematoma volume may be important early predictors of death in HICH. Proactive control and management of hematoma may reduce the mortality of HICH. PMID- 26889223 TI - Ovarian hormones ameliorate memory impairment, cholinergic deficit, neuronal apoptosis and astrogliosis in a rat model of Alzheimer's disease. AB - Ovarian hormones, including progesterone (P4) and 17 beta-estradiol (E2), have been shown to affect memory functions; however, the underlying mechanism whereby ovarian hormone replacement therapy may decrease the risk of Alzheimer's disease (AD) is currently unclear. The present study aimed to investigate the effects of P4 and E2 on spatial and learning memory in an ovariectomized rat model of AD. beta-amyloid (Abeta) or saline were stereotaxically injected into the hippocampus of the rats and, after 1 day, ovariectomy or sham operations were performed. Subsequently, the rats were treated with P4 alone, E2 alone, or a combination of P4 and E2. Treatment with E2 and/or P4 was shown to improve the learning and memory functions of the rats, as demonstrated by the Morris water maze test. In addition, treatment with E2 and P4 was associated with increased expression levels of choline acetyltransferase and 5-hydroxytryptamine receptor 2A (5-HT2A), and decreased expression levels of the glial fibrillary acidic protein in the hippocampus of the rats. Furthermore, E2 and P4 treatment significantly attenuated neuronal cell apoptosis, as demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling assays; thus suggesting that the ovarian hormones were able to protect against Abeta-induced neuronal cell toxicity. The results of the present study suggested that the neuroprotective effects of P4 and E2 were associated with amelioration of the cholinergic deficit, suppression of apoptotic signals and astrogliosis, and upregulation of 5-HT2A expression levels. Therefore, hormone replacement therapy may be considered an effective strategy for the treatment of patients with cognitive disorders and neurodegenerative diseases. PMID- 26889224 TI - Lung cancer in which the hypothesis of multi-step progression is confirmed by array-CGH results: A case report. AB - The pathogenesis of lung cancer has not been fully elucidated and biological markers acting as predictors of tumor evolution and aggressiveness remain unidentified. The multi-step hypothesis, suggesting a progression from adenomatous hyperplasia (AAH) to adenocarcinoma (AC) through bronchioalveolar carcinoma (BAC), was highlighted in a previous cytogenetic study performed in a single case. The present study reports the results of an array-comparative genomic hybridization (a-CGH) analysis performed on the DNA obtained from the previously reported case that presented AAH, BAC and AC in one lung. The a-CGH results confirm and support the previous cytogenetic observations with new data, clearly supporting the hypothesis of a multi-step carcinogenic process in the lung. PMID- 26889225 TI - Evaluation of the early response and mechanism of treatment of Parkinson's disease with L-dopa using 18F-fallypride micro-positron emission tomography scanning. AB - The aim of the present study was to investigate the use of 18F-fallypride micro positron emission tomography (micro-PET) imaging in the evaluation of the early therapeutic efficacy of L-dopa in the treatment of Parkinson's disease (PD) and the underlying mechanism. 18F-fallypride was synthesized and its specific binding with dopamine (DA) receptors in normal mouse brain was studied. Following the establishment of a mouse model of PD, the animals were divided into normal control, PD model and L-dopa treatment groups. General behavior, swimming test, locomotor activity counts, transmission electron microscopy, immunohistochemical analysis, high performance liquid chromatography-electrochemical detection and 18F-fallypride micro-PET imaging were used to study intergroup differences and the correlation between the changes of striatal uptake of 18F-fallypride and the therapeutic efficacy. The general behavioral features of PD model mice were similar to the clinical symptoms of PD patients and were alleviated after treatment. The swimming time, locomotor activity and frequency of standing posture of PD model mice were lower than those of the control mice, but had no difference from those of the control mice after L-dopa treatment. The number of tyrosine hydroxylase-positive neurons and the striatal contents of glutathione peroxidase, superoxide dismutase, DA and its metabolites 3,5 dihydroxyphenylacetic acid and homovanillic acid in the PD group were lower than those in the control group, but were significantly improved following the treatment; the significant reduction in DOPAC/DA and HVA/DA ratios post treatment suggested that the rate of DA metabolism decreased significantly. The striatal malondialdehyde content in the PD group increased compared with that in the control group, but was reduced after L-dopa treatment. Micro-PET imaging indicated that the uptake of 18F-fallypride in the mouse striatum of the PD group was lower than that of the control group and was significantly increased after the treatment. The mechanism of treatment of PD with L-dopa in mice may involve increasing the number of TH-positive cells and DA receptor levels, as well as reducing the rate of DA metabolism; such changes can be noninvasively observed in vitro by 18F-fallypride imaging. PMID- 26889226 TI - Effect of acute hypervolemic hemodilution of 6% hydroxyethyl starch 130/0.4 on the EC50 of propofol at two clinical endpoints in patients. AB - Preoperative acute hypervolemic hemodilution (AHHD) is a technique used in anesthesia to reduce the number of blood cells lost during intraoperative bleeding. The aim of the present study was to evaluate the effect of the hypervolemic hemodilution of 6% hydroxyethyl starch 130/0.4 on the EC50 of propofol at two clinical endpoints. A total of 20 patients undergoing AHHD following epidural anesthesia were studied, and 20 patients who did not receive hemodilution were used as a control group. All patients were American Society of Anesthesiologists grade I, aged 20-40 years and undergoing hip arthroplasty surgery. In the AHHD group, 10 ml/kg lactated Ringer's solution was infused over 20 min at the same time as the epidural test dose. The infusion was followed by the infusion of 6% hydroxyethyl starch 130/0.4 over 30 min. Patients in the control group received 10 ml/kg Ringer's solution over 50 min. Propofol was then delivered by a Diprifusor target-controlled infusion. The predicted blood and effect-site propofol concentrations were recorded at loss of consciousness (LOC) and return of consciousness (ROC). Probit analysis was used to estimate the values for predicted blood and effect-site concentrations at the two clinical endpoints. The results showed that the potency of propofol was decreased during AHHD. Compared with the controls, the predicted blood and effect-site concentrations of propofol at LOC were higher in patients of the hemodilution group, resulting in higher EC50 values (P=0.001 and 0.025, respectively). At ROC, the effect-site EC50 was 2.9 ug/ml [95% confidence interval (CI), 2.8-3.0] in hemodilution patients and 2.5 ug/ml (95% CI, 2.2-2.6) in control patients (P=0.001). With AHHD, the LOC time was significantly longer and the propofol dose was higher, while ROC times were comparable. In conclusion, AHHD increases the requirement for propofol at LOC and prolongs LOC time. Patients with AHHD recovered consciousness at higher effect-site concentrations of propofol. Thus, the induction dose of propofol should be increased during AHHD. PMID- 26889227 TI - Evolution of entecavir-resistant hepatitis B virus during entecavir and adefovir dipivoxil combination therapy. AB - The emergence of entecavir (ETV) resistance is rare, particularly in a longitudinal study. The aim of the present study was to characterize the evolution of ETV-resistant variants during antiviral therapy using entecavir monotherapy followed by ETV-adefovir dipivoxil (ADV) combination therapy. The study included a prospective cohort of 53 consecutive chronic hepatitis B (CHB) patients. During the 60-month period of ETV therapy, 2 patients exhibited ETV resistance and their medical records were comprehensively reviewed. A total of 25 consecutive serum samples were regularly collected from the 2 patients. All the samples were used to characterize the evolution of the polymerase gene mutations using pyrosequencing. The linkage of the variants was analyzed from 87 reverse transcriptase sequences of 3 selective samples using clone sequencing. The 2 patients presented with viral breakthrough during ETV monotherapy. In patient A, the rtL180M, rtS202G and rtM204V mutant variants were detected using pyrosequencing prior to virological breakthrough. Although the viral load declined following the administration of ADV, the ETV-resistant variants were persistently dominant in the viral populations. In patient B, the rtL180M, rtM204I and rtM204V mutants were present in ~70, 30 and 10% of the viral populations, respectively, at the time of study entry. In addition, rtT184F was present in ~20% of the viral population during virological breakthrough, at month 24. The rtL180M, rtT184F and rtM204V were predominant during the combination treatment. Clonal analysis further revealed that the rtS202G or rtT184F was in all cases co-localized with rtL180M and rtM204V in any single virus isolate clone. The results of the present study indicate that the addition of ADV therapy with ETV for treating ETV-resistant mutation may not inhibit the replication of ETV-resistant variants that developed previously in lamivudine-treated CHB patients. PMID- 26889228 TI - Effect of Chaihu-Shugan-San on the mRNA expression of the 5-HT1A receptor and cellular proliferation in the hippocampus of epileptic rats with depression. AB - Chaihu-Shugan-San (CHSGS) is a herbal preparation that has been shown to effectively relieve neurologic impairment and reduce depression. However, the efficacy of CHSGS in the treatment of patients with epilepsy with depression is unknown. Therefore, in the present study, adult rats were exposed to chronic mild stress following the establishment of chronic pilocarpine-induced epilepsy. Subsequently, a sucrose consumption test and open-field test (OFT) were performed to assess depression-like behavior. Rats were randomly divided into four groups: Control, model, fluoxetine (1.8 g/kg) and CHSGS (2.7 g/kg) groups. The control and model groups received normal saline. The mRNA expression levels of the 5 hydroxytryptamine 1A (5-HT1A) receptor and the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in the hippocampal dentate gyrus were detected using reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis, respectively. Treatment administration was conducted by once daily intragastric perfusion for 28 days. The mRNA expression levels of the 5-HT1A receptor, the number of BrdU-labeled cells in the hippocampal dentate gyrus, the consumption of sucrose, and frequency of vertical and horizontal movement scores in the OFT were enhanced in the fluoxetine and CHSGS groups compared with the model group (P<0.05). However, no statistically significant difference was detected between the fluoxetine and CHSGS groups. These data suggest that CHSGS is able to increase the expression of 5-HT1A receptor mRNA and cellular proliferation in the hippocampal dentate gyrus in epileptic rats with depression, and thus effectively improve certain symptoms of depression. PMID- 26889229 TI - The influence of genetic polymorphisms in TLR4 and TIRAP, and their expression levels in peripheral blood, on susceptibility to sepsis. AB - The present study aimed to investigate whether genetic polymorphisms in the Toll like receptor (TLR)-4 and Toll/interleukin-1 receptor (TIR)-associated protein (TIRAP) genes, and/or their expression levels, influence the susceptibility of a patient to sepsis. A total of 106 patients with sepsis were divided into two groups on the basis of their acute physiology and chronic health evaluation (APACHE) II scores: i) Sepsis group A (APACHE II <20) and ii) Sepsis group B (APACHE II >20). In addition, 100 healthy volunteers were enrolled into the control group. Polymerase chain reaction-restriction fragment length polymorphism assay was used to detect the following genetic polymorphisms: The Ser180Leu allele of the TIRAP gene and the Asp299Gly and Thr399I1e alleles of the TLR4 gene. Furthermore, the protein expression levels of TLR4 and TIRAP were analyzed using an enzyme-linked immunosorbent assay. Genetic polymorphisms were not detected for the TLR4 and TIRAP genes; however, the protein expression levels of TLR4 and TIRAP differed significantly between the control, sepsis A and sepsis B groups (P<0.01). An APACHE II score of 20 was used as a baseline in order to differentiate sepsis severity. Pearson analysis demonstrated that TLR4 and TIRAP protein expression levels were positively correlated with sepsis severity (r=0.931 and 0.972; P<0.05), and TLR4 protein expression levels were positively correlated with those of TIRAP (r=0.936; P<0.05). The results of the present study suggested that the protein expression levels of, but not genetic polymorphisms in, TLR4 and TIRAP were associated with the severity of sepsis. PMID- 26889230 TI - Characteristic expression and significance of CCL19 in different tissue types in chronic rhinosinusitis. AB - Chronic rhinosinusitis (CRS) is a heterogeneous disease, with varying immunological and histopathological features. The CC chemokine ligand 19 (CCL19) can stimulate T cells and antigen-presenting cells into secondary lymphoid node formation, as observed in allergic rhinitis, inflammatory bowel disease and other inflammatory disorders. The purpose of this study was to investigate the expression and significance of CCL19 in CRS. Samples of uncinate process mucosa or nasal polyps were taken from patients with CRS (without or with nasal polyps) and normal controls during surgery. Hematoxylin and eosin, periodic acid Schiff and Masson trichrome staining were used for analysis of the nasal polyps. Western blot and immunofluorescence were used to detect CCL19 expression in the nasal polyps and normal nasal mucosa tissues. Spearman correlation analysis was used to analyze the association between CCL19 and blood eosinophil counts. The results showed that CCL19 protein levels in CRS (with or without nasal polyps) were significantly upregulated compared with those in controls. CCL19 expression in eosinophilic CRS was significantly higher than in non-eosinophilic CRS. CCL19 expression in fibroinflammatory and edematous type CRS with nasal polyps was higher than in controls; the upregulation was greater in the edematous type. Immunofluorescence assays showed that CCL19 was mainly expressed by CD68+ macrophages. Spearman correlation analysis demonstrated a positive correlation between CCL19 and blood eosinophils. The upregulation of CCL19 in CRS may play a protective role by limiting eosinophil infiltration and the extent of edema to exert anti-inflammatory and immunomodulatory effects. PMID- 26889232 TI - Clinical significance of plasma levels of brain natriuretic peptide and cardiac troponin T in patients with sepsis. AB - Sepsis is a systemic inflammatory response of the body to an antigen and can become a life-threatening condition by triggering a cascade of changes leading to multiple organ failure such as heart failure. The aim of the present study was to examine the changes of the plasma levels of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) in patients with sepsis and to analyze their prognostic significance. A total of 38 hospitalized patients with sepsis were included in the present study. The patients were divided into the survival and death groups, based on their prognosis. The plasma levels of NT-proBNP and cTnT for the two groups were measured for all the patients on the 1st, 3rd and 7th day of admission. The plasma levels of NT-proBNP and cTnT between the two groups were compared and their association with prognosis were analyzed. The plasma levels of NT-proBNP and cTnT in the death group were significantly higher than those in the survival group (P<0.05). Additionally, a positive assocciation of the plasma levels of NT-proBNP and cTnT was identified (P<0.05). In conclusion, the plasma levels of NT-proBNP and cTnT may be used as routine clinical biomarkers to assess the prognosis of patients with sepsis. PMID- 26889231 TI - Variations in oxidative stress markers in elite basketball players at the beginning and end of a season. AB - The aim of the present study was to examine the changes occuring in the redox status in male basketball players at the beginning and end of a highly competitive season. For this purpose, the redox status of 14 professional athletes of a European basketball club was examined at 2 different time points, at the beginning (phase 1) and at the end of the season (phase 2). The redox status was assessed in blood using conventional oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS), protein carbonyls (CARB) and the total antioxidant capacity (TAC) in plasma, as well as glutathione (GSH) levels and catalase (CAT) activity in erythrocytes. Moreover, a new static oxidation reduction potential marker (sORP) was assessed in plasma. Our results revealed that sORP was significantly increased by 9.6% and GSH levels were significantly decreased by 35.0% at phase 2 compared to phase 1, indicating the induction of oxidative stress due to excessive exercise. Moreover, TAC was significantly increased by 12.9% at phase 2 compared to phase 1, indicating the activation of adaptive responses for counteracting oxidative stress. The CARB and TBARS levels were not significantly altered between the 2 phases, although there was a significant correlation (r=0.798) between the sORP and CARB levels. Furthermore, the variations in these markers between athletes were examined. We found that 3 markers exhibited a similar response between athletes, that is, sORP was increased in all 14 athletes, TAC was increased in 13 and the GSH levels were decreased in 14. However, the other 3 markers (i.e., TBARS, CARB and CAT) exhibited marked variations between the athletes, suggesting that the optimal approach with which to counteract (e.g., antioxidant supplementation) the observed increase in oxidative stress is the individualized examination of the redox status of athletes using a series of markers. This would allow the identification of athletes affected by severe oxidative stress and inflammation, and would thus indicate when necessary intervention measures are required to improve their health and performance. PMID- 26889233 TI - Association between postoperative thromboembolism prophylaxis and complications following urological surgery. AB - Thromboembolism represents the most significant complication and cause of non surgical mortality in major urological surgery. The aim of the present study was to assess the association between the type of pharmacological thromboembolism prophylaxis and the postoperative complication rate in a cohort of patients undergoing major urological surgery. All consecutive patients treated with major urological surgery between December 2011 and March 2013 were evaluated. For each patient, clinical and demographic data, as well as information on the post surgical complications and the type of pharmacological thromboembolism prophylaxis, were collected. In total, 453 patients (mean age, 63.36+/-12.05 years) were recruited (43.5% for prostate surgery, 33.1% for renal surgery, 12.1% for bladder surgery and 11.3% for other surgery). Postoperative blood transfusions were required in 50 cases (11.0%). A total of 32 patients (7.1%) underwent re-intervention due to the occurrence of grade >=3 complications, with a readmission rate of 2.0%. According to the Clavien-Dindo Classification, the complications were grade 1 in 36.0% of the cases, grade 2 in 19.4%, grade 3 in 6.0%, grade 4 in 2.0% and grade 5 (mortality) in 0.7%. Only 1 case of deep venous thrombosis not associated with pulmonary thromboembolism was observed. Univariate analyses showed a significant negative association (higher risk of complications) between the use of >4,000 IU enoxaparin as the thromboembolism prophylaxis and postoperative blood transfusion rate (P=0.045), re-intervention rate (P=0.001) and the occurrence of grade >=3 complications (P<0.001). Multivariate analysis confirmed the significant association between the use of >4,000 IU enoxaparin and both re-intervention rate (P=0.013) and occurrence of grade >=3 complications (P=0.002). High doses of enoxaparin (>4,000 IU) may lead to an increased risk of re-intervention and severe postoperative complications following major urological surgery. Randomised, controlled trials comparing the effect of different types of pharmacological thromboembolism prophylaxis on postoperative complications following major urological surgery are required. PMID- 26889234 TI - Bioavailability and safety study of resveratrol 500 mg tablets in healthy male and female volunteers. AB - Over the past few decades, trans-resveratrol has received widespread attention as a preventive agent for numerous diseases. Several studies have demonstrated that it has significant biological and pharmacological properties. Trans-resveratrol has been reported to possess anti-oxidant, anti-inflammatory, anticarcinogenic, antidiabetic, anti-aging, cardioprotective and neuroprotective properties, which can be relevant in chronic diseases and longevity in humans. The aim of the present study was to investigate the rate and extend of absorption, and also the safety of resveratrol following a single 500 mg oral dose. This was an open label, single dose, one period, bioavailability study in 15 healthy volunteers under fasting conditions. Blood samples were collected at predefined time points up to 24 h after resveratrol administration, and plasma concentrations of resveratrol and its conjugated (glucuronated and sulphated) metabolites were determined using a validated high performance liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters, including Cmax, AUC0-t, AUC0 inf, Tmax, T1/2 and MRT, were determined from plasma concentration-time profiles and found to be in good agreement with previously reported data. Cmax and AUC0 inf were lower for resveratrol when compared with the values for its glucuronated and sulphated metabolites. Cmax for resveratrol, glucuronated resveratrol and sulphated resveratrol were 71.2+/-42.4 ng/ml, 4,083.9+/-1,704.4 ng/ml and 1,516.0+/-639.0 ng/ml, respectively, while the AUC0-inf values were 179.1+/-79.1 ng/ml, 39,732.4+/-16,145.6 ng/ml and 14,441.7+/-7,593.2 ng/ml, respectively. No adverse reactions associated with resveratrol were reported during the study. The plasma concentrations of resveratrol (free and conjugated) were in agreement with those mentioned in the literature, and were adequate to promote the pharmacological activities of resveratrol. In conclusion, resveratrol 500 mg tablets were well-tolerated by all participants of the study. PMID- 26889236 TI - Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model. AB - A growing body of evidence suggests that hydrogen is a novel, selective antioxidant that exerts a protective effect against organ damage. The present study investigated the effect of hydrogen-rich saline on corticosteroid-induced necrosis of the femoral head in an animal model established using prednisolone. A total of 30 healthy, male, adult New Zealand white rabbits were randomly divided into two groups: Hydrogen-rich saline (treated with hydrogen-rich saline via intraperitoneal injection) and placebo (treated with normal saline). At the set time-points, the structure of the femoral head was examined using a microscope; the concentrations of glutathione (GSH), lipid peroxide (LPO), vascular endothelial growth factor (VEGF) and thrombomodulin (TM) in the plasma were measured and the microvessel density was quantified. The results showed that hydrogen-rich saline significantly decreased the levels of VEGF, TM and LPO and increased the GSH level in steroid-associated necrosis of the femoral head in the rabbit model. A significant increase in the microvessel density was observed in the hydrogen-rich saline group. Histopathological staining confirmed the results of the biochemical analysis. The present study demonstrates that hydrogen treatment may alleviate steroid-associated osteonecrosis by inhibiting oxidative stress. Hydrogen-rich saline may provide an alternative treatment for steroid associated necrosis of the femoral head. PMID- 26889235 TI - Vagus nerve stimulation attenuates myocardial ischemia/reperfusion injury by inhibiting the expression of interleukin-17A. AB - Interleukin (IL)-17A has an important role in myocardial ischemia/reperfusion (I/R) injury, and vagal stimulation (VS) has been demonstrated to exert cardioprotective effects. The present study aimed to investigate the effects of VS on a rat model of myocardial I/R injury, and detected an association between VS and IL-17A. Anesthetized rats underwent VS (2 msec; 10 Hz) or were treated with anti-IL-17A neutralized monoclonal antibodies (mAbs) (200 ug; iv), and subjected to ischemia for 30 min prior to 4 h reperfusion. The following parameters were measured: Infarct size; lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD) and caspase-3 activity levels; tumor necrosis factor (TNF)-alpha and IL-6 expression levels; and the percentage of terminal deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL) positive cells. High mobility group box 1 protein (HMGB1) and IL-17A expression levels were assessed by immunoblotting. Following 4 h reperfusion, VS was able to significantly decrease the infarct size and the activity levels of LDH and CK (P<0.05). Furthermore, VS administration significantly suppressed the increased MDA and decreased SOD activity levels, and significantly reduced caspase-3 activity and the percentage of TUNEL-positive cells (P<0.05). Treatment with anti-IL-17A mAbs demonstrated the same effects as VS. Furthermore, VS was able to significantly inhibit the increased expression levels of TNF-alpha, IL-6, HMGB1 and IL-17A induced by I/R (P<0.05). The results of the present study suggested that VS may attenuate myocardial I/R injury by reducing the expression of inflammatory cytokines, oxidative stress and the apoptosis of cardiomyocytes. Furthermore, VS may induce cardioprotective effects, which may be associated with the inhibition of IL-17A expression. PMID- 26889237 TI - Effects of a combination of puerarin, baicalin and berberine on the expression of proliferator-activated receptor-gamma and insulin receptor in a rat model of nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is a prevalent disease, with a clinical spectrum ranging from simple fatty liver disease to nonalcoholic steatohepatitis and cirrhosis. Puerarin, baicalin and berberine are herbal products widely used in Asia, which are believed to possess therapeutic benefits for alleviating the symptoms of NAFLD. In the present study, a rat model of NAFLD, induced by a high fat diet, was established and orthographical experimentation was used to investigate the effects of various combinations of puerarin, baicalin and berberine on the hepatic expression of proliferator-activated receptor (PPAR) gamma and insulin receptor (IR). The present study demonstrated that serum levels of total cholesterol, alanine transaminase and low-density lipoproteins were significantly decreased in the puerarin-dominated groups (P<0.05 vs. the model group), whereas the concentrations of tumor necrosis factor-alpha and interleukin 6 were significantly improved in the baicalin- and berberine-dominated groups (P<0.05 vs. the model group). Furthermore, as compared with the control group, the levels of PPAR-gamma/IR mRNA and protein expression were significantly decreased in the model group (P<0.01), and significantly increased in the rosiglitazone group and some of the orthogonal experiment groups (P<0.01). In conclusion, a combination of puerarin, baicalin and berberine induced favorable effects on NAFLD by upregulating hepatic PPAR-gamma and IR expression levels, and different proportions of monomer compositions exerted variable positive effects on various stages of NAFLD. PMID- 26889238 TI - Fat-1 gene inhibits human oral squamous carcinoma cell proliferation through downregulation of beta-catenin signaling pathways. AB - The omega-3 fatty acid desaturase (fat-1) gene encodes the enzyme that converts omega-6 polyunsaturated fatty acids (PUFAs) to omega-3 PUFAs. Numerous studies have suggested that the ratio of omega-6/omega-3 PUFAs has an impact on tumorigenesis. To investigate the biological function of the fat-1 gene in human oral squamous cell carcinoma (OSCC), the fat-1 gene was introduced into OSCC cells by transfection. The uptake of the gene was confirmed by reverse transcription-polymerase chain reaction and analyzed using gas chromatography. The antitumor effects and mechanisms of the fat-1 gene were evaluated by studying cell survival and tumor growth in vitro and in vivo. Gas chromatography results revealed that the cells transfected with the fat-1 gene had a higher omega 3/omega-6 PUFA ratio than cells transfected with the control vector. An MTT and DNA fragmentation assay indicated that the presence of the fat-1 gene in vitro significantly decreased OSCC cell proliferation and significantly increased the rate of apoptosis. Similar antitumor effects of the fat-1 gene were also observed in vivo. Immunohistochemistry analysis confirmed that Tca8113 cell tumors displayed a significant reduction in cell growth and cell survival following the introduction of the fat-1 gene. The current study suggests that the inhibitory effect of the fat-1 gene on tumor growth may be a result of a reduction in the expression of the tumor survival protein beta-catenin. The results also support the theory that the ratio of omega-3/omega-6 PUFAs has an impact on OSCC tumor growth. The findings of the study provide notable molecular insight into the theory suggesting that omega-3 PUFAs are an intermediate for the chemoprevention and treatment of human OSCC. PMID- 26889239 TI - Atypical skin reaction in a patient treated with gefitinib for advanced lung cancer: A case report and review of the literature. AB - Gefitinib is a selective epidermal growth factor receptor tyrosine kinase inhibitor utilized for the treatment of advanced non-small cell lung carcinoma. The most commonly reported adverse event during gefitinib therapy is skin rash, particularly a papulopustular acne-like eruption. Cutaneous toxicities can affect treatment compliance and the quality of life of the patient. The present study reports a case of gefitinib-induced atypical skin reaction in a 73-year-old woman with advanced non-small cell lung cancer, who developed a squamous-crusted eruption on her face after 4 weeks of oral treatment with gefitinib at a dose of 250 mg/day. The patient was treated with 100 mg minocyclin (2 tablets/day, orally) and with ryfamicin topically. A complete resolution of the lesions was observed 2 weeks later. The present case report explored the pathogenesis of this skin manifestation, focusing on the underlying immunological mechanisms. A review of the literature concerning skin reactions to gefitinib was also conducted. PMID- 26889240 TI - Clinicopathological observation of primary lung enteric adenocarcinoma and its response to chemotherapy: A case report and review of the literature. AB - Primary lung enteric adenocarcinoma is a rare type of invasive lung carcinoma. Its morphology and immunohistochemistry are those of colorectal carcinoma, but there is no associated primary colorectal carcinoma. The present study describes the case of a 53-year-old female who presented with an irritating cough and a mass around the right sternoclavicular joint. Comprehensive evaluation revealed involvement of the mediastinum, lungs, right sternoclavicular joint and right kidney. Biopsies from the mediastinal and right sternoclavicular joint tumors showed features of adenocarcinoma. Immunohistochemistry was positive for cytokeratin (CK)20 and caudal type homeobox transcription factor 2, and negative for CK7, thyroid transcription factor-1 and napsin A. Genotypic analysis identified the expression of wild-type epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine-protein kinase B-Raf and UDP glucuronosyltransferase 1-1. There was no expression of echinoderm microtubule associated protein-like 4-anaplastic lymphoma kinase and a moderate expression of excision repair cross-complementation group 1, ribonucleoside-diphosphate reductase large subunit and tubulin beta-3 chain. A strong expression of thymidylate synthase and 677TC genotype expression of methylenetetrahydrofolate reductase was observed. Gastroscopy, enteroscopy, colorectal colonoscopy and positron emission tomography-computed tomography failed to find evidence of a gastrointestinal malignancy and primary lung enteric adenocarcinoma was diagnosed. The presence of multiple metastases did not permit curative surgery. The patient was treated with 3 monthly cycles of the XELOX chemotherapy regimen; the response was poor with progression of supraclavicular lesions. Treatment was switched to the TP regimen for 4 monthly cycles, which resulted in a significant reduction in the size of the lung lesions; however, the supraclavicular lesion responded poorly to the treatment. The patient then received 2 cycles of the FOLFIRI regimen; however, the lung and right supraclavicular lesions progressed, causing increased right upper limb pain. The pain was alleviated by palliative surgery. Following surgery, the DP regimen was employed. Follow-up of the patient remains ongoing. The present findings suggest that the early diagnosis and treatment of primary lung enteric adenocarcinoma is likely to improve patient outcome. PMID- 26889241 TI - Esophageal mucosa exfoliation induced by oxalic acid poisoning: A case report. AB - This study reports the case of a 44-year-old woman with oral oxalic acid poisoning. As the illness progressed, the patient exhibited severe metabolic acidosis, large-area esophageal mucosa injury and acute kidney injury, which required dialysis. A guide wire slipped out of position during the process of hemodialysis and moved back and forth in the veins, but was removed successfully by interventional endovascular treatment. However, the patient's esophageal mucosa exfoliated, which lead to severe benign esophageal stenosis and dysphagia. Balloon distention was conducted twice in the upper digestive tract using X-ray location in combination with a dumb-bell bladder and interventional wire. The patient exhibited convulsions, shock, embolism and loss of consciousness while undergoing the second balloon distention procedure. Following symptomatic treatment, the patient eventually remained in a stable condition, the digestive tract expansion procedure was not resumed and a jejunostomy was performed in order to facilitate enteral nutrition, which was administered via the jejunum and had little stimulatory effect on the pancreas. Following various treatments, the patient's condition improved markedly, with renal function returning to normal. PMID- 26889242 TI - Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1. AB - The aim of the present study was to investigate the capacity of signal-induced proliferation-associated protein 1 (SIPA-1) to regulate bladder cancer cell invasion and metastasis. BIU-87 and T24 cells were transfected with the SIPA gene and SIPA short hairpin (sh)RNA, respectively. Western blot analysis was conducted to analyze the expression levels of SIPA-1, Ras-related protein 1 (Rap1), Rap1 guanosine triphosphate (Rap1GTP), E-cadherin and zona occludens-1 (ZO-1). Cell motility and invasion were evaluated in vitro using wound and Transwell assays. Transfected cells were inoculated into the pelvic region of BALB/c nude mice, and the number of resulting tumors was recorded after 6 weeks. Western blot analysis revealed that expression levels of E-cadherin and ZO-1 were reduced in the cells with enhanced levels of SIPA-1. By contrast, the levels of E-cadherin and ZO-1 were elevated in the cells in which SIPA-1 was knocked down. In comparison with untransfected cells, the cells with reduced levels of SIPA-1 exhibited reduced wound closure and fewer cells crossed the chamber in the Transwell experiment, whereas the cells with enhanced levels of SIPA-1 exhibited increased migration and invasion In vivo, an increased tumor count was obtained in the mice with elevated levels of SIPA-1. Therefore, the results of the present study indicate that SIPA-1 is able to regulate bladder cancer cell metastasis and invasion by reducing the expression of E-cadherin and ZO-1. PMID- 26889243 TI - Kimura's disease of the right cheek: A case report. AB - Kimura's disease (KD), a chronic inflammatory disease of uncertain etiology, manifests as a painless subcutaneous swelling in the head and neck region that involves major salivary glands and regional lymph nodes. To date, the majority of cases of KD have been documented in Asian males aged 20-30 years. However, the number of reported cases of KD involving the oral and maxillofacial area is limited, and since the masses appear similar to cysts or benign tumors, the establishment of an accurate pre-operative diagnosis is challenging. The accurate diagnosis of KD is considered to require surgical excision followed by histopathological examination. In the current case, a 39-year-old man was admitted to hospital in October 2011 with a swelling evident on his right cheek. Surgical excision was performed, and histopathological observation was carried out. The formation of a lymphoid nodule accompanied by the vigorous proliferation of small blood vessels, eosinophilic infiltration and thickened cell walls were observed. No sign of recurrence of the mass has yet been observed, on the basis of the telephone follow-up interviews. These findings provide a novel insight useful in the diagnosis of KD in the oral and maxillofacial area. PMID- 26889244 TI - siRNA-mediated downregulation of GluN2B in the rostral anterior cingulate cortex attenuates mechanical allodynia and thermal hyperalgesia in a rat model of pain associated with bone cancer. AB - It has previously been suggested that the upregulation of GluN2B-containing N methyl D-aspartate receptors (GluN2B) within the rostral anterior cingulate cortex (rACC) may contribute to the development of chronic pain. The present study used a rat model of bone cancer pain in order to investigate whether lentiviral-mediated delivery of small interfering RNAs targeting GluN2B (LV GluN2B) could attenuate pain associated with bone cancer, by selectively decreasing GluN2B expression within the rACC. Sprague Dawley rats were inoculated with osteosarcoma cells into the intramedullary space of the right tibia in order to induce persistent bone cancer-associated pain. Intra-rACC administration of the lentiviral siRNA was performed in the tumor bearing rats; and reverse transcription-quantitative polymerase chain reaction and western blotting were performed in order to detect the expression levels of GluN2B. Pain behavior changes were evaluated via paw withdrawal threshold and latency determinations. Marked and region-selective decreases in the mRNA and protein expression levels of GluN2B were detected in the rACC following the intra-rACC administration of LV GluN2B. Furthermore, the rats also exhibited pain behavior changes corresponding to the decreased levels of GluN2B. By post-operative day 14, inoculation of osteosarcoma cells had significantly enhanced mechanical allodynia and thermal hyperalgesia in the rats, which were subsequently attenuated by the intra-rACC administration of LV-GluN2B. Notably, the paw withdrawal threshold and latency of the tumor-bearing rats had recovered to normal levels, by day 14 post administration. The results of the present study suggest that GluN2B within the rACC may be a potential target for RNA interference therapy for the treatment of pain associated with bone cancer. Furthermore, the lentiviral vector delivery strategy may be a promising novel approach for the treatment of bone cancer pain. PMID- 26889245 TI - Apigenin protects against bleomycin-induced lung fibrosis in rats. AB - Apigenin is a non-toxic and non-mutagenic flavone that exists abundantly in numerous herbs and vegetables. Apigenin exerts anti-proliferative and anti inflammatory properties. The aim of the present study was to investigate the effects of apigenin on bleomycin-induced lung fibrosis in rats. A single intratracheal instillation of bleomycin (5 mg/kg) was administered and rats were sacrificed on 7 and 28 days post bleomycin instillation. The instillation of bleomycin resulted in decreased body weight and an increase in the lung index. In addition, bleomycin administration increased the hydroxyproline content, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta levels and decreased the superoxide dismutase (SOD) activity in the rat lung tissues. Excessive collagen deposits were detected in the lung tissues in bleomycin-treated rats compared with normal control rats. Notably, the oral administration of apigenin (10, 15 and 20 mg/kg/day) appeared to prevent the fibrotic process. The treatment suppressed the increases in hydroxyproline content, MPO activity, TNF-alpha and TGF-beta levels and attenuated the reduction of SOD activity that were induced by bleomycin. Furthermore, excessive collagen deposition was inhibited by the apigenin treatment. Collectively, these results suggest that apigenin may function as a potent anti-inflammatory and anti-fibrotic agent against bleomycin-induced lung fibrosis. PMID- 26889247 TI - Treatment of choroid metastasis from lung adenocarcinoma with bevacizumab containing chemotherapy: A case report. AB - The occurrence of ocular metastasis from lung cancer is uncommon. The present study reports the case of a 69-year-old female patient with lung adenocarcinoma who was found to have a metastatic lesion in the left choroid at the time of presentation. As the patient was found to have a mutation in the epidermal growth factor receptor, treatment with gefitinib was administered; however, the response was evaluated as a progressive disease. Thereafter, the patient received chemotherapy with carboplatin, pemetrexed and bevacizumab. Radiological imaging revealed shrinkage of the primary lesion and choroidal metastasis, and the visual power of the left eye was also shown to improve. Therefore, the present case report demonstrated the efficacy and safety of systemic bevacizumab therapy in combination with a platinum doublet for the treatment of choroid metastasis, with morphological and functional improvements observed with regard to the choroidal metastatic tumor. PMID- 26889246 TI - Infantile Pompe disease: A case report and review of the Chinese literature. AB - Pompe disease, also known as glycogen storage disease type II, is caused by acid maltase deficiency, and can lead to lysosomal glycogen storage. The primal manifestations may be observed in children and adults, and also in infants. In general, the clinical spectrum in infants is more progressive and lethal than that in older patients. This case report describes the case of a newborn who was found to have cardiac hypertrophy, hepatomegaly and elevated serum enzyme levels, which was characterized by an aspartate aminotransferase level of 95 U/l, lactate dehydrogenase level of 778 U/l and creatine kinase level of 1,299 U/l. On the basis of the clinical signs and laboratory results, dried blood spots from the baby were tested to determine the acid alpha-glucosidase (GAA) activity, and the result confirmed that the GAA activity was only 0.10 pmol/punch/h (normal reference range, 2.88-89.02 pmol/punch/h) at pH 3.8, which was clearly lower than the normal range, leading to a diagnosis of Pompe disease. Pompe disease is incurable, and before the introduction of enzyme replacement therapy (ERT), pain relief was the main treatment. Recognizing this disease earlier and starting ERT in infants prior to the development of clinical symptoms is likely to improve the quality of life of patients. PMID- 26889249 TI - Effect of the topical application of calcipotriol on the expression levels of zinc finger protein A20 and nuclear factor-kappaB in the skin lesions of patients with psoriasis vulgaris. AB - The aim of the present study was to explore the effect of the topical application of calcipotriol on the expression levels of zinc finger protein A20 and nuclear factor-kappaB (NF-kappaB) in the skin lesions of patients with psoriasis vulgaris. The calcipotriol ointment was topically applied twice a day for 6 weeks by 26 patients with psoriasis vulgaris. At the end of weeks 2, 4 and 6 after the first application of calcipotriol ointment, the clinical efficacy and Psoriasis Area and Severity Index (PASI) score were compared with those prior to treatment. The expression of zinc finger protein A20 and NF-kappaB in the skin lesions prior to and following treatment with calcipotriol was measured by immunohistochemical staining and western blotting. At the end of week 6, the clinical effectiveness rate of calcipotriol was higher compared with that at the end of weeks 2 and 4 (chi2=8.12 and 9.06, respectively; P<0.05). The PASI score declined significantly at the end of weeks 2, 4 and 6 (t=9.37, 10.54 and 12.43; P<0.05, 0.05 and 0.001, respectively). At the end of week 6, the expression levels of zinc finger protein A20 and NF-kappaB were significantly lower compared with those prior to treatment (chi2=3.65 and 4.17, respectively; P<0.01). The expression levels of the two proteins were higher in the skin lesions of patients with psoriasis vulgaris prior to the initiation of treatment than in the skin of a normal control group. Following the 6-week treatment with calcipotriol, the expression levels of the two proteins in the psoriasis skin lesions were significantly lower than they were prior to treatment (P<0.01). Thus, the present study found that in addition to the typical pathway of NF-kappaB being targeted in the treatment of psoriasis with calcipotriol, the zinc finger protein A20 may also modulate the inflammatory response of psoriasis. PMID- 26889248 TI - Effect of rikkunshi-to treatment on chemotherapy-induced appetite loss in patients with lung cancer: A prospective study. AB - The aim of the present study was to investigate the effect of rikkunshi-to, a Japanese herbal medicine, on post-chemotherapeutic appetite loss. Patients with unresectable lung cancer, who were treated with carboplatin (CBDCA)-containing, cisplatin (CDDP)-containing or non-platinum chemotherapy between 2011 and 2014, were recruited for the prospective study. For each course of chemotherapy, the patients were randomized into two groups, with or without a rikkunshi-to prescription. In patients treated with CBDCA-containing chemotherapy, food intake at day 7 following the initiation of chemotherapy in the rikkunshi-to treatment group was significantly higher compared with the group not treated with rikkunshi to (P=0.0078). However, a significant improvement in food intake with rikkunshi to treatment was not observed in the CDDP-containing and non-platinum chemotherapy groups. An improved assessment of the incidence rate of chemotherapy induced appetite loss is essential for achieving adequate control. The results of the present study indicated the possibility of the clinical application of rikkunshi-to for improving post-chemotherapeutic appetite loss. PMID- 26889250 TI - Role of soluble programmed death-1 (sPD-1) and sPD-ligand 1 in patients with cystic echinococcosis. AB - The programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) signaling pathway is a negative regulatory mechanism that inhibits T cell proliferation and cytokine production. Soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1), are also involved in regulation of the PD-1/PD-L1 signaling pathway. In the present study, the expression levels of sPD-1 and sPD-L1, as well as those of T helper (Th)1 [including interleukin (IL)-2 and interferon gamma], Th2 (including IL-4, IL-6 and IL-10) and Th17 (including interleukin 17) cell cytokines, were measured in the sera of patients with cystic echinococcosis (CE). Measurements were performed prior to and following after surgery and treatment with cyclic albendazole to investigate the effects of sPD-1 and sPD-L1 in patients with CE. Cytokine expression levels were measured using cytokine bead array and the expression levels of sPD-1 and sPD-L1 were measured using ELISA. In addition, in vitro stimulation was used to detect whether sPD-L1 has a negative regulatory effect on cytokine secretion or homeostasis. The present study observed significantly higher levels of sPD-L1 in patients with CE compared with healthy controls. Significantly elevated levels of Th2 cytokines in the sera of patients with CE were also observed. The results also suggest that there is an imbalanced expression of Th1 and Th2 cells during CE. In addition, it was demonstrated that sPD-1 and sPD-L1 are regulatory factors to the PD-1/PD-L1 signaling pathway, each having opposite effect, suggesting that they regulate the immune response to CE infection by creating a dynamic balance. In conclusion, sPD-L1 may play an important role in maintaining homeostasis in hosts with CE. PMID- 26889251 TI - Protective effects of SIRT1 in patients with proliferative diabetic retinopathy via the inhibition of IL-17 expression. AB - Diabetic retinopathy (DR) is a chronic microvascular complication of diabetes that may lead to loss of vision. The pathogenesis of DR is complex and elevated expression levels of T helper (Th)17 cells and interleukin (IL)-17 have been suggested to be associated with the development and progression of DR. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide+-dependent histone deacetylase that is downregulated in patients with DR. Previous studies have demonstrated that SIRT1 is capable of inhibiting the production of IL-17. In the present study, 19 patients with proliferative diabetic retinopathy (PDR) and 20 non diabetic controls with idiopathic macular epiretinal membranes were recruited and the SIRT1 expression levels of excised specimens were analyzed using immunohistochemistry. IL-17 expression levels in the sera from patients with PDR and controls were determined by enzyme-linked immunosorbent assay (ELISA). Furthermore, SIRT1 mRNA and protein expression levels in peripheral blood mononuclear cells (PBMCs) from the two groups were analyzed following culture with or without a SIRT1 activator, resveratrol. IL-17 expression levels in the supernatants of PBMCs were determined using ELISA and the results demonstrated that IL-17 expression levels were increased in the sera of patients with PDR, as compared with the controls. Furthermore, increased expression levels of SIRT1 and IL-17 were detected in fibrovascular membranes and PBMCs harvested from patients with PDR, respectively. Notably, SIRT1 mRNA and protein expression levels were decreased in the PBMCs of patients with PDR and IL-17 production was inhibited following SIRT1 activation. The results of the present study indicated that imbalanced IL-17 and SIRT1 expression levels may contribute to the pathogenesis of DR, and SIRT1 may have a protective role in PDR by inhibiting the production of IL-17. PMID- 26889252 TI - Paeoniflorin attenuates hepatic ischemia/reperfusion injury via anti-oxidative, anti-inflammatory and anti-apoptotic pathways. AB - During liver surgery, hepatic blood flow needs to be blocked in order to reduce bleeding, which inevitably results in hepatic ischemia/reperfusion injury (HI/R). Paeoniflorin (PF) is the main active ingredient of the traditional Chinese herbal medicine peony, which has been shown to exert anti-oxidative and anti-apoptotic properties. In the present study, a mouse model of HI/R was generated by clamping the hepatoportal vein, hepatic artery, and hepatic duct of BALB/c mice with a vascular clamp for 30 min, followed by reperfusion for 6 h under anesthesia. Six mice in the three PF treatment groups (5, 10 and 20 mg/kg) were then injected with PF, via the tail vein. A sham group, consisting of six mice that did not undergo the procedure, and a vehicle group, consisting of 6 mice that underwent the procedure but subsequently received injections of physiological saline only, were used as controls. Liver injury was indicated by serum levels of the enzymes alanine transaminase (ALT) and aspartate transaminase (AST). The activities of oxidative stress biomarkers, including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA), were also measured. Furthermore, the activity of caspase-3 was analyzed in hepatic tissue using a commercial kit. Treatment with PF significantly attenuated HI/R injury histologically, as compared with the vehicle group. In addition, significant reductions in the serum levels of ALT and AST were observed in the PF-treated ischemic mice. Furthermore, treatment with PF enhanced the activities of hepatic tissue SOD, GSH and GSH-PX, but decreased the MDA content. Treatment of ischemic mice with PF markedly reduced the expression levels of inflammatory mediators, including nuclear factor-kappaB, tumor necrosis factor-alpha, interleukin (IL)-6, and IL-1beta, and decreased the HI/R injury-induced expression of caspase-3. The results of the present study suggest that PF attenuates the HI/R injury of mice via anti-oxidative, anti-inflammatory and anti-apoptotic activities. PMID- 26889253 TI - Association of antibiotic resistance with SHV-12 extended-spectrum beta-lactamase in Enterobacter cloacae. AB - The association between antibiotic resistance and SHV-12 extended-spectrum beta lactamase (ESBL) in Enterobacter cloacae remains unknown. The aim of the present study was to investigate the prevalence of both chromosome- and plasmid-borne SHV 12 ESBL genes in Enterobacter cloacae. Transmission of the SHV-12 ESBL gene was explored, and the risk factors for antibiotic resistance in E. cloacae were analyzed. Polymerase chain reaction (PCR) results showed that 58 out of the 100 isolates carried the SHV-12 ESBL gene: 34.48% of them occurred in the chromosome, 48.28% were plasmid-borne and 17.24% appeared in both. Enterobacterial repetitive intergenic consensus-PCR tests detected 82 chromosomal genotypes. Conjugation assays showed that 70.00% of plasmid-borne SHV-12 ESBL genes were successfully transconjugated into E. coli C600 and that the antibiotic resistance phenotype of E. cloacae was partially (84%) or completely (10%) transferred. A significantly higher SHV-12 ESBL detection rate was found in patients with underlying conditions and/or complications compared with those without (P<0.05). The detection of SHV-12 ESBL-producing E. cloacae from vertical transmission varied significantly across clinical departments and age groups (P<0.05), with the highest rates in the intensive care unit and the group of patients aged >=60 years. The present results indicate that the location and transmission efficiency of SHV-12 ESBL are closely correlated with the antibiotic resistance of E. cloacae. PMID- 26889254 TI - Protocatechuic aldehyde inhibits TNF-alpha-induced fibronectin expression in human umbilical vein endothelial cells via a c-Jun N-terminal kinase dependent pathway. AB - Fibronectin (FN) is one of the most important extracellular matrix proteins and plays an important role in the pathogenesis of atherosclerosis (AS). The aim of the present study was to evaluate the effect of a potent, water-soluble antioxidant, protocatechuic aldehyde (PA), which is derived from the Chinese herb Salvia miltiorrhiza, on the expression of FN in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-alpha (TNF-alpha). The pharmacological effects of PA on the production of FN were investigated using ELISA and western blot analysis. In addition, ELISA and western blot analysis were used to examine the activation and suppression of the mitogen-activated protein kinase (MAPK) pathways and nuclear factor (NF)-kappaB in TNF-alpha stimulated HUVECs, in order to explore the underlying pharmacological mechanism of PA. The inhibitory effect of PA on the total generation of reactive oxygen species (ROS) in TNF-alpha-stimulated HUVECs was assessed using 2',7' dichlorofluorescein diacetate. Pretreatment of HUVECs with PA (0.15, 0.45 and 1.35 mM) for 18 h markedly attenuated the TNF-alpha-stimulated FN surface expression and secretion in a dose-dependent manner. Intracellular ROS generation and the expression of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c Jun N-terminal kinase (JNK) and p38 MAPK (p38) were significantly induced by TNF alpha (2 ng/ml) in HUVECs. TNF-alpha-induced ROS generation and JNK activation were inhibited by PA in a concentration-dependent manner. By contrast, ERK1/2 and p38 activation was not significantly affected by PA. Pretreatment of HUVECs with PA for 18 h markedly attenuated TNF-alpha-stimulated NF-kappaB activation. In conclusion, the present findings suggest that PA inhibits TNF-alpha-induced FN expression in HUVECs through a mechanism that involves ROS/JNK and NF-kappaB. PMID- 26889255 TI - Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene. AB - The aim of the present study was to investigate the optimal mobilization plan in autologous peripheral blood stem cell transplantation for the treatment of diabetic foot and to observe its clinical curative effect. A total of 127 patients with diabetic foot were treated with different doses of granulocyte colony stimulating factor (G-CSF) to mobilize their hematopoietic stem cells. Subsequently, the extracted stem cell suspension was injected into the ischemic lower extremities along the blood vessels in the areas presenting with pathological changes. Following the treatment, the intermittent claudication distance, skin temperature, ankle brachial index and pain scores of the patients were evaluated. In addition, the associations among the mobilization time, doses and peripheral blood CD34+ level were analyzed. The collection efficiency of the stem cells was associated with the dose of G-CSF and the mobilization time. Following the injection of the autologous peripheral blood stem cell suspension, the ischemic area of the patients was improved significantly. In conclusion, autologous peripheral blood stem cell transplantation can promote the establishment of collateral circulation in patients with diabetic foot, and the optimal time for gathering stem cells is closely correlated with the peripheral blood CD34+ level. PMID- 26889256 TI - Upper gastrointestinal safety and tolerability of oral alendronate: A meta analysis. AB - Osteoporosis (OP), which is a common bone disease associated with reduced bone mineral density and disordered bone microstructure, may result in an increased risk of bone fracture. The present study aimed to investigate the frequency of alendronate (Aln)-associated upper gastrointestinal tract adverse events (GIAEs) in postmenopausal women with OP. The following databases were searched in order to identify relevant studies: Medline (using PubMed as the search engine), Embase, the Web of Science and the Cochrane Central Register of Controlled Trials (up to December 2014). Studies were selected for inclusion if they were randomized, double-blind, placebo-controlled trials, which had investigated the safety of Aln versus a placebo for the treatment of postmenopausal women with OP. The primary outcomes of the included studies were total adverse events (AEs) and upper GIAEs, whereas individual upper GIAEs were considered as secondary outcomes. The general characteristics and outcomes of each study were abstracted by two independent researchers, and Review Manager 5.3 software was used for data syntheses and the meta-analysis. A total of nine studies, including 15,192 randomized patients, met the inclusion criteria and contributed to some or all of the meta-analysis outcomes. The Mantel-Haenszel method was used to calculate risk ratios, and their 95% confidence intervals (CI) were determined using either the fixed or random effects model, depending on the level of heterogeneity. The relative risk (95% CI) of AEs associated with Aln treatment, as compared with the placebo group, was 1.01 (0.97-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to AEs was 1.04 (0.91-1.19). In addition, the relative risk (95% CI) of upper GIAEs was 1.02 (0.99-1.06), and the relative risk (95% CI) of discontinued Aln treatment due to upper GIAEs was 1.23 (0.97-56). In addition, these results remained robust to sensitivity analyses. The results of the present study suggested that Aln has a good GI tract tolerability, and that daily treatment with 10 mg Aln sodium does not increase the risk of GIAEs in postmenopausal women with OP. PMID- 26889257 TI - Adrenergic stimulation alters the expression of inflammasome components and interleukins in primary human monocytes. AB - Prior to their release, interleukin (IL)-1beta and IL-18 are cleaved to their bioactive forms by a multiprotein complex known as an inflammasome, which is comprised of a number of elements that are subject to nuclear factor-kappaB dependent transcription. Catecholamines have been indicated to exert an enhancing effect on the IL-1beta release. The aim of the present study was to determine whether alterations in inflammasome gene expression may be responsible for the modified IL-1beta and IL-18 secretion following lipopolysaccharide (LPS) and catecholamine co-stimulation. Monocytes were isolated from the peripheral blood of 21 healthy volunteers using CD14+ microbeads. Following stimulation with LPS (2 ug/ml) and/or phenylephrine (PE; 10 uM) for 24 h, the supernatants were subjected to ELISA to evaluate the ex vivo protein expression levels of IL-1beta and IL-18. In addition, the gene expression levels of inflammasome components associated with the cleavage of IL-1beta and IL-18, including NLRP1, NLRP3, caspase-1 and PYCARD were determined using polymerase chain reaction. The results indicated that LPS significantly increased IL-1beta expression compared with the unstimulated control samples. Co-stimulation with LPS + PE significantly enhanced IL-1beta expression compared with LPS alone. Furthermore, IL-18 expression was significantly reduced by LPS and LPS + PE co-stimulation. The gene expression levels of IL-18, NLRP1, caspase-1 and PYCARD were comparable in the LPS- and LPS + PE-stimulated cells. LPS significantly induced the expression levels of IL 1beta and NLRP3, and to a lesser degree, the expression of NLRP1, compared with the control. By contrast, PE markedly induced the expression levels of IL-18 and NLRP1, while LPS reduced the gene expression of IL-18. In conclusion, adrenergic stimulation suppressed NLRP3 expression and enhanced NLRP1 expression, indicating that NLRP3 may regulate IL-1beta secretion and NLRP1 may regulate the release of IL-18. PMID- 26889259 TI - Inhibitory effect of bone morphogenetic protein-2 on the proliferation of giant cell tumor of bone stromal cells in vitro. AB - The inhibitory effect of bone morphogenetic protein-2 (BMP-2) on the proliferation of giant cell tumor of bone stromal cells (GCTSCs) has not been fully elucidated. Therefore, the aim of this study was to evaluate the role of recombinant human BMP-2 (rhBMP-2) in the growth of GCTSCs. The effects of exposure to different concentrations of rhBMP-2 (0, 10, 100 and 300 ng/ml) for 1, 3, 5 and 7 days on GCTSC proliferation were examined by 3-(4,5-dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, the effect of treatment with rhBMP-2 (0 or 10 ng/ml) for 48 h on the cell cycle pattern of GCTSCs was examined by flow cytometry. The apoptosis-inducing effect of rhBMP-2 (0 or 10 ng/ml) in GCTSCs was also determined by flow cytometry after 48 and 72 h. In addition, western blot assays were conducted to determine whether rhBMP-2 acts on non-Smad mitogen-activated protein kinase (MAPK) signaling pathways, namely extracellular signal-regulated kinase (ERK1/2), p38 and c-jun-N-terminal kinase (JNK) pathways. The proliferation of GCTSCs treated with rhBMP-2 (10, 100 or 300 ng/ml) for 5 or 7 days was significantly inhibited in a non dose-dependent and non-time-dependent manner (P<0.05). The treatment of GCTSCs with rhBMP-2 (10 ng/ml) for 48 h had no effect on cell cycle distribution. The apoptosis of GCTSCs induced by exposure to rhBMP-2 (10 ng/ml) for 48 or 72 h was significant (P<0.05). Expression levels of phospho-ERK1/2, phospho-p38 and phospho-JNK increased significantly when GCTSCs were treated with rhBMP-2 (10 ng/ml) for 72 h (P<0.05). The results indicate that rhBMP-2 has no stimulatory effect on GCTSC growth. However, it may lead to the apoptosis of GCTSCs by non-Smad MAPK signaling pathways. PMID- 26889258 TI - Effects of rhein lysinate on D-galactose-induced aging mice. AB - The aim of the present study was to investigate the anti-aging effects of rhein lysinate (RHL), and to explore its mechanism of action in a D-galactose-induced aging mouse model. Aging was induced by D-galactose (100 mg/kg/day) that was subcutaneously injected to animals for 8 weeks. RHL was simultaneously administered once a day by intragastric gavage. The appetite, mental condition, body weight and organ index of the mice were monitored. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were determined, and the levels of malondialdehyde (MDA) in the liver, kidney and serum were measured by appropriate assay kits. Western blot analysis was used to detect proteins associated with age. The results indicated that RHL may improve the appetite, mental state and organ conditions of the model mice, improve the activities of SOD and GSH-Px, reduce MDA levels and modulate the expression of age-associated proteins (Sirtuin 1, p21 and p16) in D-galactose-induced mice. Therefore, RHL may be effective at suppressing the aging process through a combination of enhancing antioxidant activity, scavenging free radicals and modulating aging-associated gene expression. PMID- 26889260 TI - Anti-leucine-rich glioma-inactivated 1 limbic encephalitis: A case report and literature review. AB - This study describes the case of a 41-year-old woman admitted for anterograde memory loss, right facial grimacing and right arm posturing that had begun 1 month previously. Cranial magnetic resonance-diffusion weighted imaging and fluid-attenuated inversion recovery imaging revealed a hyperintense signal in the left hippocampus and right basal ganglia, but no contrast enhancement. An electroencephalogram revealed rhythmic sharp and slow waves and rhythmic theta build-ups in the left temporal area. Single-photon emission computed tomography showed increased regional blood flow perfusion in the left cerebral frontal lobe and the right basal ganglia. The cerebrospinal fluid was normal, with the exception of the presence of leucine-rich glioma-inactivated 1 (LGI1) antibodies, and LGI1 antibodies were also found in the blood serum. The presence of the antibodies, the faciobrachial dystonic seizures (FBDSs) and the memory loss indicated limbic encephalitis. After 3 months of immunotherapy, the patient was free from epileptic seizures and had undergone a partial memory restoration. FBDSs alone justify the immediate initiation of immunotherapy, even prior to laboratory confirmation of the disease, as early treatment limits the duration of the illness. PMID- 26889262 TI - Endoscopic biopsy of a B-cell lymphoma involving the entire ventricular system: A case report. AB - A 62-year-old male suffering from vomiting and mild preceding nausea for 15 days was examined in the present case report. Magnetic resonance imaging revealed a homogeneously enhancing cluster-like lesion involving the lateral, third and fourth ventricles. An endoscopic biopsy was performed, and histopathological examination led to the diagnosis of a high-grade diffuse large B-cell lymphoma. To the best of our knowledge, the present study reports the first case of a primary lymphoma involving the entire ventricular system. Therefore, primary lymphomas should be considered in the list of ventricular tumors. An endoscopic biopsy requires minimal invasion to obtain an adequate tissue sample, and frequently leads to the correct diagnosis and subsequent treatment protocols. PMID- 26889261 TI - Effects of preserving different veins on flow-through flap survival: An experimental study. AB - Flow-through skin flap grafting is becoming widely used for the reconstruction of skin and soft tissue defects, particularly for patients with poor blood supply around the defect. However, the treatment of the veins remains controversial. In the present study, 5*2-cm skin flaps were created on the left inner thighs of rabbits in order to investigate the effects of various treatments of the veins on the survival of a flow-through skin flap. A femoral artery perforator running through the flap was preserved. Five groups were established in which no veins, one superficial vein (SV), one accompanying vein (AV), one SV plus one AV, or all trunk veins (control) were retained. The percentage of flap area survival was determined on day 10. On days 3, 5, 7 and 9, tissues were harvested from the skin flaps and immunohistochemical analysis was performed in order to count the number of microvessels. Western blot analysis was subsequently completed in order to determine the expression levels of vascular endothelial growth factor (VEGF). The flap areas in which no veins were retained demonstrated significantly reduced survival rates on day 10, as compared with those in the other four groups (P<0.01). Furthermore, flaps with the retention of a SV also demonstrated reduced survival rates, as compared with the AV, AV plus SV and all veins groups (P<0.01); however, there no significant differences were detected between the latter three groups (P>0.05). Immunohistochemical analysis on day 3 detected a greater number of microvessels in the flaps of the control group, as compared with the flaps of the other groups. Furthermore, the AV and AV plus SV groups demonstrated a greater number of microvessels, as compared with the SV and no vein groups, and he no vein group demonstrated the fewest microvessels. No significant differences were found between the AV, AV plus SV and control groups on day 5, 7 and 9. Western blot analysis on day 5 demonstrated that the expression levles of VEGF were significantly increased in the flaps of the AV, AV plus SV and control groups, as compared with those in the SV and no vein groups. No significant differences were detected between the former three groups, and increased VEGF expression levels were detected in the flaps of the SV group, as compared with the no vein group. The flow-through flap grafts with no retained veins barely survived. Anastomosing one AV was adequate for flap survival; however, further studies are required in order to investigate the survival of flow-through flaps in more detail. PMID- 26889263 TI - Dynamic contrast-enhanced MRI serves as a predictor of HIFU treatment outcome for uterine fibroids with hyperintensity in T2-weighted images. AB - The aim of the present study was to investigate the efficacy of dynamic contrast enhanced magnetic resonance imaging (MRI) in predicting the outcome of using ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for the treatment of uterine fibroids with T2 hyperintensity under MRI. A total of 131 uterine fibroids from 131 patients that appeared hyperintense under T2-weighted MRI were analyzed. The uterine fibroids were subjectively categorized into slight, irregular or regular enhancement groups, according to pretreatment dynamic contrast-enhanced MRI in the arterial phase within 60 sec after the injection of gadolinium. The non-perfused volume (NPV), which is indicative of successful ablation, was represented as the non-perfused area inside the uterine fibroids on enhanced MRI scans following treatment. Additionally, the treatment duration, treatment efficiency, sonication duration, energy efficiency ratio and any adverse events were recorded. The results indicated that the average NPV ratio for all the treated fibroids was 68.5%, while the average NPV ratios for fibroids with slight, irregular or regular enhancement were 84.7, 70.6 and 57.1%, respectively. Fibroids with regular enhancement were associated with the lowest NPV ratio and the lowest treatment efficiency, but exhibited the highest energy effect ratio and an elevated risk of severe adverse effects. The results of the present study indicate that hyperintense uterine fibroids with slight and irregular enhancement in the arterial phase of dynamic contrast-enhanced MRI are suitable for USgHIFU treatment. By contrast, uterine fibroids with regular enhancement were associated with the lowest treatment efficacy and safety. PMID- 26889264 TI - Recurrent sialoliths after excision of the bilateral submandibular glands for sialolithiasis treatment: A case report. AB - Sialolithiasis is a common disease that is characterized by the obstruction of the salivary gland. Sialolithiasis mainly affects the submandibular glands and the Wharton's duct. However, bilateral sialolithiasis is a rare condition. In addition, recurrence of sialoliths subsequent to surgical excision of the submandibular gland for the treatment of sialolithiasis has been rarely reported. The present study reported a case presenting with recurrent sialoliths with sialadenitis in the residual Wharton's duct following the excision of bilateral submandibular glands. An 81-year-old man presented with a solid and painful mass in the left submandibular area. The patient had a history of bilateral submandibular sialolithiasis, and had undergone excision of bilateral submandibular glands with the right Wharton's duct 4 years earlier. Computed tomography scans demonstrated two calculi in the residual Wharton's duct, which were surgically removed without any complications. The present study discussed the mechanisms underlying sialolith formation subsequent to the excision of submandibular glands. PMID- 26889265 TI - Combination of deep sea water and Sesamum indicum leaf extract prevents high-fat diet-induced obesity through AMPK activation in visceral adipose tissue. AB - The aim of the present study was to evaluate the protective effects of a combination of deep sea water (DSW) and Sesamum indicum leaf extract (SIE) against high-fat diet (HFD)-induced obesity and investigate its molecular mechanisms in adipose tissue. ICR mice were randomly divided into three groups: HFD control (HFC), DSW and DSW + 125 mg/kg SIE (DSS) groups. The mice in the HFC group had free access to drinking water while those in the DSW and DSS groups had free access to DSW. The mice in the DSS group were treated with SIE once per day for 8 weeks. The mice in all three groups were allowed to freely access a HFD. Compared with the HFC group, the DSS group showed lower body weight gain and serum levels of glucose, triglycerides and leptin. Histological analyses of the epididymal white, retroperitoneal white and scapular brown adipose tissue of mice in the DSS group revealed that the adipocytes were markedly decreased in size compared with those in the HFC group. Moreover, DSS significantly increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC) in mice epididymal adipose tissues. Furthermore, DSS upregulated the expression levels of lipolysis associated mRNA, specifically peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and cluster of differentiation 36 (CD36), and energy expenditure associated mRNA, namely uncoupling protein 2 (UCP2) and carnitine palmitoyltransferase-1 (CPT1) in the epididymal adipose tissues. By contrast, DSS suppressed the expression of the lipogenesis-related gene sterol regulatory element-binding protein-1 (SREBP1) at the mRNA level. These results suggest that DSS is effective for suppressing body weight gain and enhancing the lipid profile. PMID- 26889267 TI - Palliation double stenting for malignant biliary and duodenal obstruction. AB - The surgical management of patients with malignant biliary and duodenal obstruction is complex. Tumor excision is no longer possible in the majority of patients with malignant obstructive jaundice and duodenal obstruction. The aim of the present study was to evaluate the effectiveness of intraluminal dual stent placement in malignant biliary and duodenal obstruction. In total, 20 patients with malignant obstructive jaundice and duodenal obstruction, including 6 with pancreatic carcinoma, 11 with cholangiocarcinoma, 1 with duodenal carcinoma and 2 with abdominal lymph node metastasis, were treated with intraluminal stent placement. Bile duct obstruction with late occurrence of duodenal obstruction was observed in 16 cases, and duodenal obstruction followed by a late occurrence of bile duct obstruction was observed in 3 cases, while, in 1 case, bile duct obstruction and duodenal obstruction occurred simultaneously. After X-ray fluoroscopy revealed obstruction in the bile duct and duodenum, stents were placed into the respective lumens. Percutaneous transhepatic placement was employed for the biliary stent, while the duodenal stent was placed perioraly. The clinical outcomes, including complications associated with the procedures and patency of the stents, were evaluated. The biliary and duodenal stents were successfully implanted in 18 patients and the technical success rate was 90% (18/20). A total of 39 stents were implanted in 20 patients. In 2 cases, duodenal stent placement failed following biliary stent placement. Duodenal obstruction remitted in 15 patients, and 1 patient succumbed to aspiration pneumonia 5 days after the procedure. No severe complications were observed in any other patient. The survival time of the 18 patients was 5-21 months (median, 9.6 months), and 6 of those patients survived for >12 months. The present study suggests that X-ray fluoroscopy-guided intraluminal stent implantation is an effective procedure for the treatment of malignant biliary and duodenal obstruction. PMID- 26889266 TI - Pyogenic granuloma in a patient with psoriasis successfully treated by 5 aminolevulinic acid photodynamic therapy: A case report. AB - Pyogenic granuloma (PG) is an acquired benign vascular tumor of unknown etiology. In the present case report, PG was detected in a 49-year-old Chinese male patient with chronic plaque psoriasis. The psoriasis lesions on the finger where the granuloma had developed had been scratched excessively, as declared by the patient. No retinoid therapeutic agents were used during treatment. The patient responded poorly to cryotherapy and surgical curettage. However, following one session of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), signs of improvement were demonstrated 1 week after the treatment, and 1 month following treatment, there were no signs of reoccurrence. Although a report demonstrating treatment success in one patient may be inadequate to estimate the true efficiency of ALA-PDT, dermatologists may consider ALA-PDT as an alternative therapy for stubborn PG. PMID- 26889268 TI - Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress. AB - The aim of the present study was to investigate the effects of Schisandra chinensis (S. chinensis) and Rhodiola rosea (R. rosea) on rats subjected to 5 h of stress, induced by water-floating followed by treadmill exercise. Hypothalamus pituitary-adrenal (HPA) activity and c-Fos and Fos-related antigen 2 (Fra-2) mRNA expression levels in the hypothalamus of the rats were evaluated. Rats were distributed into four groups: S. chinensis (n=12), R. rosea (n=10), stress control (n=10) and quiet control (n=8). Following a training period of 6 consecutive days, the S. chinensis, R. rosea and stress control groups underwent a 3-h water-floating session in the presence of feline predators immediately followed by 2 h treadmill running to induce psychological and physical stress. Following compound stress induction, the serum levels of corticosterone (CORT), adrenocorticotropic hormone and interleukin-1beta and the mRNA expression levels of hypothalamic corticotropin-releasing hormone (CRH), neuropeptide-Y, c-Fos and Fra-2 were evaluated using enzyme-linked immunosorbent assay, radioimmunoassay and quantitative polymerase chain reaction, respectively. The results indicated that S. chinensis and R. rosea markedly decreased the stress-induced elevation of CRH and peripheral CORT levels. The mRNA expression levels of c-Fos and Fra-2 in the hypothalamus were significantly increased after 5 h compound stress, and reduced levels of c-Fos expression were detected in rats treated with R. rosea. Thus, S. chinensis and R. rosea exert an anti-stress effect in rats subjected to stress by balancing the HPA axis, and possibly by reducing the expression of c Fos in the hypothalamus. PMID- 26889269 TI - Effects of different doses of dexmedetomidine on heart rate and blood pressure in intensive care unit patients. AB - The aim of the present study was to observe and compare the sedative effect of different doses of DEX on heart rate (HR) and blood pressure (BP) in critically ill patients admitted to intensive care units (ICUs). The study included patients that were retained in ICUs and required sedation between January and March 2014. Patients were excluded if they had a BP of >200 mmHg, a HR of <60 bpm or were in a state of shock. The included patients were randomized into three groups: Group A, 1.0 ug/kg/10 min DEX; group B, 0.5 ug/kg/10 min DEX; and group C, 0.4 ug/kg/h DEX. After receiving these initial designated doses of DEX via an intravenous (IV) infusion pump for 10 min, the patients were maintained continuously at an identical dose of 0.4 ug/kg/h DEX. Ramsay score, HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), breathing rate (BR) and peripheral capillary oxygen saturation (SpO2) were recorded prior to the IV pump infusion and at 2, 4, 6, 8, 10, 60, 120, 180 and 240 min following infusion. Patients in groups A and B achieved sedation more rapidly compared with those in group C (P<0.05). HR decreased more significantly at 8 and 60 min after the initial IV pump infusion with DEX in groups A and B compared with group C (P<0.05). SBP decreased significantly at 10 min after IV pump infusion in group A compared with groups B and C (P<0.05). No significant difference existed in the SBP reduction trend between the three groups during the maintenance period. Therefore, the routine dose of DEX (0.4 ug/kg/h) provides an ideal sedative effect in ICU patients. The recommended loading dose for a more rapid sedation is 0.5 ug/kg/h. High loading doses of DEX via IV pump infusion should be avoided in elderly individuals, patients with acute exacerbation of chronic obstructive pulmonary disease and anemic patients, in whom combination medication, such as midazolam or propofol, may be considered when necessary. PMID- 26889270 TI - Snail mediates invasion through uPA/uPAR and the MAPK signaling pathway in prostate cancer cells. AB - Epithelial-mesenchymal transition (EMT) is a process by which cancer cells acquire mesenchymal properties, such as induction of vimentin, while epithelial associated genes like E-cadherin are lost. This enables cells to be more metastatic. Factors that are able to induce EMT include growth factors such as transforming growth factor-beta (TGF-beta) and epidermal growth factor, and transcription factors such as Snail. Snail-induced EMT promotes migration and invasion and we hypothesized that this may be mediated by the activity of urokinase-type plasminogen activator (uPA) and its receptor (uPAR). LNCaP, 22Rv1 and ARCaP human prostate cancer (CaP) cells stably transfected with empty vector control (Neo) or constitutively active Snail exhibited increased cell invasion. Superarray analysis revealed an upregulation in uPA and uPAR RNA expression in Snail-transfected ARCaP cells compared with that of a Neo control. In addition, the protein expression levels of Snail, uPA and uPAR were measured by western blot analysis which showed that overexpression of Snail increased uPA and uPAR protein levels. The activity of uPA in conditioned media was measured using an ELISA which revealed that uPA activity was elevated in LNCaP, 22Rv1 and ARCaP cells overexpressing Snail. Additionally, transient silencing of uPAR in ARCaP cells overexpressing Snail using short interfering RNA resulted in abrogation of Snail-mediated invasion. Snail overexpression was associated with increased extracellular-signal-regulated kinase activity, and antagonism of this activity with mitogen-activated protein (MAPK) inhibitor, UO126, inhibited cell invasion and decreased uPA activity. Therefore, Snail-mediated cell invasion in human CaP cells may occur via the regulation of uPA/uPAR and the MAPK signaling pathway. PMID- 26889271 TI - Endoscopic inter laminar management of lumbar disease. AB - Discectomy for lumbar disc provides faster relief in acute attack than does conservative management. Long-term results of open, microscopy-, and endoscopy assisted discectomy are same. Early results of endoscopy-assisted surgery are better as compared to that of open surgery in terms of better visualization, smaller incision, reduced hospital stay, better education, lower cost, less pain, early return to work, and rehabilitation. Although microscopic discectomy also has comparable advantages, endoscopic-assisted technique better addresses opposite side pathology. Inter laminar technique (ILT) and trans foraminal technique (TFT) are two main endoscopic approaches for lumbar pathologies. Endoscopy-assisted ILT can be performed in recurrent, migrated, and calcified discs. All lumbar levels including L5-S1 level, intracanalicular, foraminal disc, lumbar canal and lateral recess stenosis, multiple levels, and bilateral lesions can be managed by ILT. Migrated, calcified discs, L5-S1 pathology, lumbar canal, and lateral recess stenosis can be better approached by ILT than by TFT. Most spinal surgeons are familiar with anatomy of ILT. It can be safely performed in foramen stenosis and in uncooperative and anxious patients. There is less risk of exiting nerve root damage, especially in short pedicles and in presence of facet osteophytes as compared to TFT. On the other hand, ILT is more invasive than TFT with more chances of perforations of the dura matter, pseudomeningocele formation, and cerebrospinal fluid fistula in early learning curve. Obtaining microsurgical experience, attending workshops, and suitable patient selection can help shorten the learning curve. Once adequate skill is acquired, this procedure is safe and effective. The surgeon must be prepared to convert to an open procedure, especially in early learning curve. Spinal endoscopy is likely to achieve more roles in future. Endoscopy-assisted ILT is a safer alternative to the microscopic technique. PMID- 26889273 TI - The impact of cranioplasty on cerebral blood flow and its correlation with clinical outcome in patients underwent decompressive craniectomy. AB - CONTEXT: Decompressive craniectomy is commonly use as the treatment for medically refractory intracranial hypertension. Unexpected improvement in patient's neurological status has been observed among patients that underwent cranioplasty. Restoration of cerebral blood flow (CBF) hemodynamics is one of the contributing factors. This study was conducted to determine the impact of cranioplasty on CBF and its correlation with clinical outcome. AIMS: This study was done to evaluate the effect of cranioplasty on CBF with computed tomography perfusion (CTP). It also aimed to determine the correlation between postcranioplasty CBF and clinical outcome. SETTINGS AND DESIGN: Prospective observational study. SUBJECTS AND METHODS: All patients had CTP done to determine precranioplasty CBF. CTP was repeated at 6 weeks postcranioplasty and clinical assessment at 6 and 24 weeks postcranioplasty. STATISTICAL ANALYSIS USED: Data analysis was done using Statistical Package for Social Sciences version 12.0.1. RESULTS: The median value of the ipsilateral CBF was 48.87 and 61.10 ml/min/100 g at precranioplasty and 6 weeks postcranioplasty (P < 0.001). Contralateral CBF also showed improvement from 60.55 to 71.84 ml/min/100 g (P < 0.001). Median value for mini mental state examination showed a significant difference with value of 22, 25, and 25.5 at precranioplasty, 6 and 24 weeks postcranioplasty (P = 0.001 and P < 0.001). Median value for frontal assessment battery was 12, 14.5, and 15 (P = 0.002 and P = 0.001). CONCLUSIONS: Cranioplasty can remarkably improve cortical perfusion for both ipsilateral and contralateral hemisphere. Though we are unable to establish strong correlation, between CBF and clinical outcome, cranioplasty was observed to have a therapeutic role in terms of clinical outcome improvement. PMID- 26889272 TI - Supratentorial haemangioblastoma without von Hippel-Lindau syndrome in an adult: A rare tumor with review of literature. AB - Supratentorial hemangioblastomas (HBLs) are rare, benign vascular tumors of the central nervous system neoplasms. Very scarce literature is available regarding supratentorial HBL without von Hippel-Lindau (VHL) syndrome in an adult. We reviewed the literature and PubMed advanced search showed only a few results of supratentorial HBL without VHL syndrome. We reported a rare case of cystic supratentorial HBL in 39-year-old male affecting the parietal lobe without VHL syndrome. Supratentorial HBL is a rare tumor and supratentorial HBL without VHL syndrome are even rarer. Being a rare entity, not much clinical data is currently available regarding supratentorial HBLs, thus necessitating the need for further reporting and review of such cases. PMID- 26889274 TI - Comparing monomodality treatments of low-grade intracranial arteriovenous malformation at Hospital Kuala Lumpur between 2008 and 2011: A retrospective study. AB - INTRODUCTION: Intracranial arteriovenous malformations (AVMs) of Spetzler-Martin grades (SMGs) I-III are treated using either monomodality treatments of microsurgical excision, embolization or stereotactic radiosurgery (SRS), or a combination of two or more of these treatment options. At Hospital Kuala Lumpur, we still practice monomodality treatments for AVMs of these three grades. In this study, we wanted to achieve an understanding whether monomodality treatments can achieve a satisfactory outcome of AVM nidi for patients, for up to 3 years, and to gather an objective data for AVM treatment for the Malaysian population. SUBJECTS AND METHODS: This is a retrospective review of records study. The data are acquired from case notes of patients with intracranial AVM of SMGs I to III who underwent monomodality treatment at Hospital Kuala Lumpur between 2008 and 2011. The patients were followed up with imaging for up to 3 years from the date of treatment. A total of 81 patients were recruited in this study, where 30 underwent microsurgical treatment, 27 underwent embolization, and 24 underwent SRS. RESULTS: Total obliteration of AVM nidus was achieved in 96.7% of patients who underwent microsurgery, 8.7% of patients who underwent embolization, and 79.2% of patients who underwent SRS. The modified Rankin scale (mRS) for all three groups showed an improving trend, with the microsurgery group showing the best improvement (from 70% at 3 months to 92.3% at 3 years showing favorable mRS scores). CONCLUSIONS: The AVM nidus obliteration for each treatment group is comparable to the meta-analysis published in 2011. Each modality had its own set of complications; however, most of the patients in all three groups had either static or improved mRS at the end of the 3-year follow-up. PMID- 26889275 TI - Impact of electrolyte imbalances on the outcome of aneurysmal subarachnoid hemorrhage: A prospective study. AB - BACKGROUND: Electrolyte disturbances are frequently observed during the acute and subacute period after subarachnoid hemorrhage (SAH) and may potentially worsen therapeutic outcome. This study was conducted to determine the pattern of electrolyte disturbance in the acute and subacute phase after SAH and their effect on the long-term outcome of the patients. MATERIALS AND METHODS: Fifty three patients were prospectively enrolled. The standards of care for all patients were uniformly performed. The serum levels of electrolytes (sodium, potassium and magnesium) were determined with measurements obtained on admission, 3-5 and 7-10 days after SAH. Radiographic intensity of hemorrhage (Fisher's scale), and the clinical grading (World Federation of Neurosurgical Societies grade) were documented in the first visit. The outcomes were evaluated using Glasgow outcome scale at 3 months after discharge. RESULTS: Hyponatremia was the most common electrolyte imbalance among the patients but did not worsen the outcome. Although less common, hypernatremia in the subacute phase was significantly associated with poor outcome. Both hypokalemia and hypomagnesemia were predictive of poor outcomes. CONCLUSIONS: Because electrolyte abnormalities can adversely affect the outcome, the serum levels of electrolytes should be closely monitored with serial measurements and treated properly in patients with aneurysmal SAH. PMID- 26889276 TI - Histopathological study of the outer membrane of the dura mater in chronic sub dural hematoma: Its clinical and radiological correlation. AB - BACKGROUND: A chronic subdural hematoma is an old clot of blood on the surface of the brain between dura and arachnoid membranes. These liquefied clots most often occur in patients aged 60 and older with brain atrophy. When the brain shrinks inside the skull over time, minor head trauma can cause tearing of blood vessels over the brain surface, resulting in a slow accumulation of blood over several days to weeks. AIM OF THE STUDY: To evaluate the role of membrane in hematoma evaluation and to correlate its histopathology with clinic-radiological aspects of the condition and overall prognosis of patients. MATERIAL AND METHODS: The study incorporated all cases of chronic SDH admitted to the Neurosurgery department of JLN Hospital and Research Centre, Bhilai, between November 2011 and November 2013. All such cases were analyzed clinically, radiologically like site, size, thickness in computed tomography, the attenuation value, midline shift and histopathological features were recorded. CRITERIA FOR INCLUSION: All cases of chronic subdural haematoma irrespective of age and sex were incorporated into the study. CRITERIA FOR EXCLUSION: All cases of acute subdural haematoma and cases of chronic sub dural hematoma which were managed conservatively irrespective of age and sex were excluded from the study. RESULTS: In our series of cases, the most common histopathological type of membrane was the inflammatory membrane (Type II) seen in 42.30% of cases followed by hemorrhagic inflammatory membrane (Type III) seen in 34.62% of cases while scar inflammatory type of membrane (Type IV) was seen in 23.08% of cases. No case with noninflammatory type (Type I) was encountered. PMID- 26889277 TI - A novel technique to practice using a high-speed burr for spinal anterior cervical discectomy and fusion. AB - BACKGROUND: Anterior cervical discectomy and fusion has been a successful procedure in terms of patient satisfaction in the management of cervical myelopathy and radiculopathy. The procedure involves an anterior approach to the cervical vertebral column and decompression of the neural elements. AIM: A key part of the procedure is the removal of the posterior osteophyte. This is usually performed using a high-speed burr. In inexperienced hands, this part of the procedure can be a challenging one. MATERIALS: Egg, egg cup, zinc oxide tape and high-speed burr. CONCLUSION: We describe a simple and cost effective method of practicing this manoeuver, enabling the trainee to gain sufficient confidence in handling the tool around delicate tissues. PMID- 26889278 TI - Relationship between demography, etiology, level of consciousness, and outcome of surgical intracranial suppurations of bacterial origin in a tropical tertiary center. AB - INTRODUCTION: Intracranial suppurations (ICS) of bacterial origin are associated with significant mortality and morbidity. This study aimed to review demography, etiology, level of consciousness, and outcome of surgical ICS in a tropical tertiary hospital. MATERIALS AND METHODS: All patients admitted to the neurosurgical unit within the study period of 7 years that had a surgical intervention for their ICS were prospectively included in the study. In accordance with the unit protocol, all patients in whom there was clinical suspicion of ICS had a preoperative computed tomography scan and/or magnetic resonance imaging done. The following data among others were documented and recorded electronically: demography, clinical and radiological diagnosis, etiology of ICS, admission Glasgow Coma Scale (GCS) score, type of neurosurgical intervention, mode of anesthesia, and outcome. RESULTS: Forty-nine patients were included in the study. There were 33 males with a male-to-female ratio of 2.1:1. All patients presented at least a week after the use of antibiotics. The most common type of ICS was cerebral abscess (33 patients, 67.3%). There was no statistical significant association between outcome and age group (P = 0.630), gender (P = 0.999), diagnosis (P = 0.464), etiology of ICS (P = 0.169), solitary or multiplicity of ICS (P = 0.485), or type of offending organism (P = 0.278). CONCLUSIONS: ICS usually follows otorhinological infections in our center. The surgical outcome is dependent on the admission GCS score. PMID- 26889279 TI - Correlation between Glasgow Coma Scale and brain computed tomography-scan findings in head trauma patients. AB - BACKGROUND: The study aimed to assess the relationship between computed tomography (CT) scan findings and Glasgow Coma Scale (GCS) score with the purpose of introducing GCS scoring system as an acceptable alternative for CT scan to clinically management of brain injuries in head trauma patients. MATERIALS AND METHODS: This study was conducted on hospitalized patients with the complaints of head trauma. The severity of the head injury was assessed on admission by the GCS score and categorized as mild, moderate, or severe head injury. RESULTS: Of all study subjects, 80.5% had GCS 13-15 that among those, 45% had GCS 15. Furthermore, 10.5% had GCS ranged 9-12 and 9% had GCS <8. Of all subjects, 54.5% had abnormal CT findings that of them, 77.1% categorized as mild head injury, 11.0% had a moderate head injury, and 11.9% had a severe head injury. Furthermore, of those with GCS 15, 41.0% had abnormal CT scan. Of all patients with abnormal CT findings, 33.0% underwent surgery that 61.1% categorized in mild head injury group, 13.9% categorized in moderate head injury group, and 22.2% categorized in severe head injury group. Of those with GCS equal to 15, only 27.0% underwent surgery. CONCLUSION: The use of GCS score for assessing the level of injury may not be sufficient and thus considering CT findings as the gold standard, the combination of this scoring system and other applicable scoring systems may be more applicable to stratify brain injury level. PMID- 26889280 TI - Perimesencephalic subarachnoid hemorrhage: Etiologies, risk factors, and necessity of the second angiogram. AB - AIM: In this paper, we aim to present our experience with a series of patients with PMSAH. In addition, the clinical course of perimesencephalic subarachnoid hemorrgade (PMSAH) is discussed with an evaluation of etiologies, risk factors, and the necessity for a second angiogram on follow-up. MATERIALS AND METHODS: The data for this study were obtained retrospectively from patients who were treated at the Uludag University, School of Medicine, Department of Neurosurgery, Division of Neurovascular Surgery's clinic with a diagnosis of PMSAH between January 1980 and March 2002. RESULTS: We identified a total of 24 patients, 12 male. The mean age at the time of hemorrhage was 53 +/- 12 years. In all patients, the onset was typical with a sudden severe headache. Five of the patients were Hunt-Hess Grade I, 15 were Grade II, and 4 were Grade III. The initial 4-vessel angiography was normal in 23 cases. Twenty-two had a second 4 vessel angiography, and all were normal. We observed acute hydrocephalus in 5 patients (20.8%). We did not observe re-bleeding during the follow-up of our patients. CONCLUSION: Patients with PMSAH have a particularly excellent outcome, and there is no need to evaluate these patients with repeat angiography. PMID- 26889282 TI - Comparison of intravenous labetalol and bupivacaine scalp block on the hemodynamic and entropy changes following skull pin application: A randomized, open label clinical trial. AB - BACKGROUND: The application of skull pins in neurosurgical procedures is a highly noxious stimulus that causes hemodynamic changes and a rise in spectral entropy levels. We designed a study to compare intravenous (IV) labetalol and bupivacaine scalp block in blunting these changes. PATIENTS AND METHODS: Sixty-six patients undergoing elective neurosurgical procedures were randomized into two groups, L (labetalol) and B (bupivacaine) of 33 each. After a standard induction sequence using fentanyl, propofol and vecuronium, patients were intubated. Baseline hemodynamic parameters and entropy levels were noted. Five minutes before, application of the pins, group L patients received IV labetalol 0.25 mg/kg and group B patients received scalp block with 30 ml of 0.25% bupivacaine. Following application of the pins, heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and response entropy (RE)/state entropy (SE) were noted at regular time points up to 5 min. RESULTS: The two groups were comparable with respect to their demographic characteristics. Baseline hemodynamic parameters and entropy levels were also similar. After pinning, the HR, SAP, DAP, MAP, and RE/SE all increased in both groups but were lower in the scalp block group patients. HR increased by 19.8% in group L and by 11% in group B. SAP increased by 11.9% in group L and remained unchanged in group B. DAP increased by 19.7% in group L and by 9.9% in group B, MAP increased by 15.6% in group L and 5% in group B (P < 0.05). No adverse effects were noted. CONCLUSION: Scalp block with bupivacaine is more effective than IV labetalol in attenuating the rise in hemodynamic parameters and entropy changes following skull pin application. PMID- 26889283 TI - Ventriculoperitoneal shunting. PMID- 26889284 TI - Idarucizumab: A novel antidote for reversal of dabigatran. PMID- 26889281 TI - Need for a hands-on approach to hand-offs: A study of nursing handovers in an Indian Neurosciences Center. AB - CONTEXT: Standardized nursing handovers have been known to improve outcome, reduce error, and enhance communication. Few, if any, studies on nursing handovers have been conducted in the India. AIM: The aim was to study nursing handover practices in a Neurosciences Center in India. SUBJECTS AND METHODS: This study was conducted in a 200 bedded public sector Neurosciences Center in New Delhi, to assess nursing handover practices across five wards, all shifts, weekdays, and weekends using a pretested checklist. Ten elements were observed under the categories of time, duration, process, nurse interaction, and patient communication. STATISTICAL ANALYSIS: Analysis of variance, Z-test, and Spearman's correlation coefficient. RESULTS: Totally, 525 nursing handovers revealed varying compliance levels among (63%) time, place (76%), process (82%), staff interaction (53%), and patient communication (44%) related elements. Poorer compliance was seen in morning shifts and weekends; the difference being statistically significant. Bedside handovers were more frequent during weekends and night shifts and were positively correlated with increased staff interaction and patient communication and negatively related to handover duration. Though nurses showed better adherence to process related elements, background patient information, and assessment was explained less frequently. Differences between wards were insignificant except in categories of nurse interaction and patient communication which was better in the neurosurgery than neurology wards. CONCLUSION: Study revealed a need for a system change and standardization of handovers. Greater administrative commitment, use of technology, training, and leadership development will aid in continuity of care, promote patient safety, and ensure better outcomes. PMID- 26889285 TI - Tuberculosis of the skull mimicking a bony tumor. AB - We present a rare case of calvarial tuberculosis mimicking a solitary bone tumor, which was surgically removed. A 52-year-old female presented with a right forehead swelling, which gradually enlarged over the course of 2 years, with no symptoms or raised intracranial pressure or neurological deficits. Plain and contrast-enhanced brain computed tomography scans were done, revealing a punched out lesion of the right frontal bone, with a nonenhancing lytic mass. With an initial diagnosis of an intraosseous meningioma, and later on intraoperatively thought to be a metastatic tumor, the mass was excised along with a rim of bone. Histopathological examination results came back as caseous necrosis, highly suggestive of tuberculosis. The patient was then treated with a 1 year regimen of anti-tuberculous medications. Tuberculosis of the cranium is a rare entity, and can mimic tumors or multiple myeloma. A high index of suspicion and knowledge is required for an early diagnosis. A combined surgical and medical therapy is curative. PMID- 26889286 TI - Cavernous malformation of the optic chiasm: Neuro-endoscopic removal. AB - Cavernous malformations (CMs) arising from the optic nerve and chiasm are extremely rare. In large autopsy series, CMs were estimated to range from 0.02 to 0.13% in the general population. However, with introduction of MRI, these lesions were found more often than previously thought, ranging from 0.2% to 0.4%. Only 29 cases have been reported according to our knowledge. Most patients present with drop in visual acuity and visual field. Although MRI findings of cavernous malformations have been reported, they may not be diagnostic enough. Among the 29 reported, 16 underwent total resection with good results. In some, resection was complicated by damage to the surrounding neural tissue. Surgical removal is the recommended treatment to restore or preserve vision and to eliminate the risk of future hemorrhage. However, the anatomical location and eloquence of nearby neural structures can make these lesions difficult to access and remove. CMs appear to occur in every age group (range 4 months to 84 years mean-34.6 years) ith an approximately equal male to female ratio. They typically present with chiasmal apoplexy, characterized by sudden visual loss, acute headaches, retro orbital pain, and nausea. PMID- 26889287 TI - Spontaneous thrombosis of a vein of galen malformation. AB - Vein of Galen malformation (VOGM) is a rare congenital vascular anomaly, comprising about 1% of all intracranial vascular anomalies, predominantly affecting the children less than 1 year of age. A 6-month-old infant presented with complaints of increasing head size of 3 months duration and multiple episodes of vomiting associated with refusal to feed since 7 days. He was a known case of VOGM who had initially refused treatment. Investigations revealed a spontaneously thrombosed VOGM with obstructive hydrocephalous. Child improved uneventfully with ventriculoperitoneal shunt. Spontaneous thrombosis of a VOGM is a rare occurrence and carries a better prognosis. The relevant literature is discussed with emphasis on etiopathogenesis, mechanism, and management of spontaneous thrombosis of the malformation. PMID- 26889288 TI - Intramedullary arachnoid cyst in an adult: Case report and review. AB - Arachnoid cysts in the spine are a rare entity with extradural occurrence being the commonest. Arachnoid cysts in intramedullary location are sparingly reported in elderly. We herein report a case of intramedullary arachnoid cyst in an adult female who presented with features of compressive myelopathy. PMID- 26889289 TI - Perineurioma of scalp in an infant: A case report with short review of literature. AB - Perineuriomas are rare benign peripheral nerve sheath tumor composed exclusively of perineurial cells. They have been classified into two main types according to their location - intraneural and extraneural (soft-tissue). Extraneural perineurioma are uncommon, found mostly in the soft tissue of the extremities and trunk, rare at other site. They mainly affect adults and have been sometimes described in children but are extremely rare in infants. We present a case of extraneural (soft-tissue) perineurioma of scalp in a 3-month-old infant, highlighting clinical, pathologic, and immunohistochemical features along with a discussion of the main differential diagnosis of this tumor. This is also the youngest case ever reported in the literature. PMID- 26889290 TI - Transdural retrieval of a retropulsed lumbar interbody cage: Technical case report. AB - The purpose of this case report was to describe a novel method to retrieve a herniated lumbar interbody cage. Transforaminal lumbar interbody fusion (TLIF) is an increasingly popular method of spinal fixation and fusion. Unexpected retropulsion of an interbody is a rare event that can result in intractable pain or motor compromise necessitating surgical retrieval of the interbody. Both anterior and posterior approaches to removing migrated cages may be associated with significant surgical morbidity and mortality. A 60-year-old woman underwent an L4-S1 TLIF coupled with pedicle screw fixation at a previous hospital 5 years prior to admission. She noted sudden-onset bilateral lower extremity weakness and right-sided foot drop. Magnetic resonance imaging and radiographs were notable for purely centrally herniated interbody. A posterior, midline transdural approach was used to retrieve the interbody. Situated in between nerve rootlets to the ventral canal, this virgin corridor allowed us to easily visualize and protect neurological structures while safely retrieving the interbody. The patient experienced an immediate improvement in symptoms and was discharged on postoperative day 3. At 12-month follow-up, she had no evidence of cerebrospinal fluid (CSF) leak and had returned to normal activities of daily living. While the risk of CSF leak may be higher with a transdural approach, we maintain that avoiding unnecessary retraction of the nerve roots may outweigh this risk. To our knowledge, this is the first case report of a transdural approach for the retrieval of a retropulsed lumbar interbody cage. PMID- 26889291 TI - Unusual cord transection in a patient with traumatic spondylolisthesis. AB - Spinal cord injury is one of the most debilitating injuries in patients with spinal trauma. Cord injury may range from simple cord edema to frank transection. Cord transection is the most severe form of cord injury as it results in complete and irreversible loss of all neural functions. Generally, it is a result of unstable spinal fractures with associated spondylolisthesis or spondyloptosis. Generally, the level of cord transection corresponds to the level of spinal fracture/spondylolisthesis. However, here we are presenting a case having a traumatic spinal fracture with spondylolisthesis where the level of cord transection was much higher than the level of the spinal fracture. Due to the traumatic traction, the cord distal to transection is displaced inferior leaving behind a long segment of the empty thecal sac. PMID- 26889292 TI - Intracranial plasmacytomas mimicking epidural hematoma and revealed by head trauma. AB - Presenting a case of 27-year-old female presented in our OPD on 6-12-2013 with severe headache and vomiting and no history of LOC/seizure. There was H/O head trauma 2 month back. O/E pupil of normal size and normal reaction to light and neurological status with GCS-14. CT scan showed a hyperdense left frontal chronic extradural/subdural mass lesion and midline shift of 8 mm. Peroperative there was intradural lesion as nonvascular, greyish white gelatinous solid tissue without evidence of EDH. The lesion was completely excised, and the skull the bone flap was replaced. Uneventful post operative recovery with GCS-15. Histopathological report was plasmacytoma. PMID- 26889293 TI - Lymphoma relapse presenting as neurolymphomatosis. AB - Neurolymphomatosis (NL) is a rare neurological manifestation of lymphoma characterized by malignant lymphoma cells infiltrating cranial or peripheral nerve, or their roots. We present the first reported Australian case of a patient whose initial presentation of relapsed mantle cell lymphoma was NL. Our case highlights that clinical and imaging findings of NL often mimic other neuropathies, and hence presents unique challenges that may lead to delayed diagnosis and management. We emphasize the importance of considering NL in the differential diagnosis and combining imaging with other diagnostic modalities such as lumbar puncture (LP) to aid in the diagnosis of NL particularly where there is acute neurological deterioration. PMID- 26889294 TI - Grossly calcified choroid plexus concealing foramen of Monro meningiomas as an unusual cause of obstructive hydrocephalus. AB - Various intraventricular tumors can present with calcifications; however, the choroid plexus can also have physiological calcifications. This is the first case report of meningiomas located at the bilateral foramen of Monro (FOM), concealed by a grossly calcified choroid plexus, presenting with obstructive hydrocephalus. A 60-year-old woman with disturbed consciousness was admitted by ambulance. Head computed tomography revealed significantly high-density lesions that smoothly extended from the choroid plexus of the lateral ventricles to the third ventricle. They occupied both sides of the FOM, resulting in obstructive hydrocephalus. The diagnostic endoscopic biopsy was performed using a flexible neuroendoscopic system, and an egg shell-like grossly calcified choroid plexus was found to smoothly extend toward the FOM. Resection was not selected because the calcified lesions had tightly adhered to the veins and fornix; therefore, the patient underwent ventriculo-peritoneal shunting. The lesions were histologically identified as psammomatous meningiomas with low proliferation potential (the Ki 67 labeling index was lower than 1%). She was discharged 10 days after surgery without neurological deficits. As calcifications can have tumoral and nontumoral origins, we considered neuroendoscopic exploration to be essential in order to achieve an accurate diagnosis and select optimal management. PMID- 26889295 TI - Misery of neurosurgeon: Gauzoma causing foreign body granuloma-role of radiologist. AB - Materials used in neurosurgery to achieve hemostasis may be of resorbable or nonresorbable substance and may cause foreign body granuloma if left at the operative site. Foreign body granuloma depending on clinical history may be indistinguishable from an abscess, resolving infarction, and hematoma. Here we present two cases, who had decompressive craniectomy following road traffic accident. Follow-up computerized tomography (CT) scan revealed hyperdense lobulated lesion with peripheral rim enhancement. On magnetic resonance imaging (MRI), lesions were predominantly hypointense on T1-weighted images, and hyperintense on T2-weighted images and showed a lack of restricted diffusion. In view of recent craniectomy and imaging findings diagnosis of foreign body granuloma was made. Both patients underwent surgery, intraoperatively gauze pieces were retrieved from lesions which confirmed preoperative diagnosis. The combination of CT and MRI can diagnose foreign body granuloma, especially in trauma settings. Thus, we can help the surgeon by providing the probable diagnosis for proper management. PMID- 26889296 TI - Elevated fracture of skull in pediatric age group: A series of five patients with review of literature. AB - Elevated fractures of skull in pediatric age group are rarely reported in the literature. In view of rarity, we present a series of five cases of elevated skull fracture in pediatric age group. Over a period of 1-year, we operated on five such cases. In this article, we have discussed the mode, mechanism and extent of injury, its clinico-radiological findings, course of the disease, and the management outcome. Four out of five cases improved after surgery and did not suffer any complications. Early recognition and appropriate management of compound elevated fracture in pediatric age group comes with good outcome and prevents unwanted morbidity and mortality. PMID- 26889297 TI - A curious case of spontaneously resolving closed "jigsaw" depressed skull fracture in an adolescent. AB - Spontaneously resolving depressed skull fractures have been previously reported in the pediatric age group, however they are very rare in adolescents. We report a case of spontaneously elevating depressed fracture in a 13 year old boy. Depressed skull fractures in this age group might resolve on its own but may also complicate during its course of non-operative self elevation. In the reported case, the child developed gliosis and suffered seizures two years after the trauma. Repeat scans showed almost normal skull topography with underlying gliotic changes. Although all depressed skull fractures won't complicate as such, patients without neurological deficits should also be operated to prevent any delayed complications. PMID- 26889298 TI - True aneurysm of superficial temporal artery accompanying multiple intracranial aneurysm. AB - Superficial temporal artery (STA) aneurysms are very infrequent. Moreover, true aneurysms, which are not pseudoaneurysms associated with trauma or previous surgery are even rarer. With this manuscript, authors present a case of a 79-year old woman suffering from subarachnoid hemorrhage whose radiological examinations revealed multiple intracranial aneurysms along with an STA aneurysm. This very rare case, to the best of our knowledge, the second case reported so far, might contribute to the literature and lead further investigations toward the rare association between intracranial aneurysms and STA aneurysms. PMID- 26889299 TI - Blast phase transformation of chronic myelogenous leukemia presenting with central nervous system manifestation. AB - Chronic myelogenous leukemia (CML) is the most common of all leukemia constituting 15-20% of all leukemia. The clinical course of the diseases runs in two to three phases, initial chronic phase followed by accelerated phase or blast phase. Blast phase most commonly presents clinically as fever, splenomegaly, and bone pain. Here, we present a case of CML in blast phase presenting with central nervous system manifestation in a 55-year-old patient with a brief review of the literature. PMID- 26889300 TI - Solitary fibrous tumor of the orbit. AB - Solitary fibrous tumor (SFT) is a rare spindle-cell neoplasm originating from the mesenchyme. It was originally thought to occur exclusively in the intrathoracic region but has been recently described in extrapleural sites including the orbit. SFT of the orbit is a rare lesion, which can be misdiagnosed as hemangiopericytoma, fibrous histiocytoma, meningioma, or neurofibroma. Immunohistochemistry plays an important role. We report an orbital SFT in a 39 year-old female presented with painless, progressive proptosis, and diminished vision in the right eye for the duration of 6 months. Magnetic resonance imaging demonstrated well-defined enhancing mass lesion. The patient underwent complete tumor removal through a right fronto-orbital approach, and a pathological diagnosis of the solitary fibrous tumor was made. Postoperatively, the patient was symptom-free. Clinical and pathological findings including immunohistochemistry are presented along with a brief discussion of literature. PMID- 26889301 TI - Papillary tumor of pineal region with an unusual clinical presentation: Case report and review of the literature. AB - Papillary tumor of the pineal region (PTPR) is a newly described entity, which has been recently included in the World Health Organization classification of central nervous system tumors. We report an unusual presentation of PTPR in a 17 year-old girl, which was extending into the third ventricle, along with a detailed description of morphological and immunohistochemical characteristics of PTPRs. The diagnosis of PTPR was established on immunohistopathological examination. PMID- 26889302 TI - Understanding How Intimate Partner Violence Impacts School Age Children's Internalizing and Externalizing Problem Behaviors: A Secondary Analysis of Hawaii Healthy Start Program Evaluation Data. AB - We examined the role of maternal depression and parenting stress in the relationship between intimate partner violence (IPV) and child internalizing and externalizing problems, and explored whether child gender modified these pathways. This secondary analysis used data from the Hawaii Healthy Start Program. Logistic regression models examined the associations between IPV in 1st grade and child internalizing and externalizing behaviors in 1st, 2nd, and 3rd grades. Mediation models used bootstrapping methodology and stratified models examined effect modification. Adjusted models with 214 mothers demonstrated associations between IPV and internalizing (adjusted odds ratios (aOR)=2.62; 95% CI 1.11, 6.21) and externalizing (aOR=4.16; 95% CI 1.55, 11.19) behaviors. The association with externalizing behaviors was mediated by maternal depression and parenting stress, while internalizing behaviors was mediated by depression only. Stratified models found the association between IPV and externalizing behaviors was significant for girls only. Our results support the importance of multicomponent maternal IPV interventions. PMID- 26889303 TI - [Neurobrucellosis: a treatable cause of sensorineural hearing loss not to ignore]. PMID- 26889304 TI - [Chromophobe renal cell carcinoma: about four cases and review of the literature]. PMID- 26889305 TI - [Poland syndrome]. PMID- 26889306 TI - [Extended deep vein thrombosis of the lower limb complicating medically assisted procreation : about an observation]. PMID- 26889307 TI - [Medulloblastoma in adults: report of 13 cases and literature review]. PMID- 26889308 TI - [Sign of the " molar tooth ": characteristic MRI appearance of Joubert syndrome]. PMID- 26889310 TI - Conjunctival venous malformations: a case report. PMID- 26889309 TI - Recurrent spontaneous intracerebral hemorrhage associated with polyglobulia. PMID- 26889311 TI - [The nodule of Sister Mary Joseph, a rare contributory metastasis]. PMID- 26889312 TI - Cavernous hemangioma of the bladder: an additional case managed by partial cystectomy and augmentation cystoplasty. AB - Cavernous Hemangioma of the Bladder (CHB) is benign and rare lesions. Clinical presentation has no pathognomonic signs although gross painless hematuria is the most frequent complain. CHB is suspected by cystoscopy and radiologic findings and confirmed by pathologic examinations. Management is controversial due to the bleeding risk of this highly vascularized lesion. Partial cystectomy is the treatment of choice for surgically accessible lesions. However, it appears that small lesions could be treated using transurethral resection. Since CHB is a rare case, we report another case treated successfully with a partial cystectomy associated with an augmentation cystoplasy. PMID- 26889313 TI - Chronic tophaceous gout with unusual large tophi: case report. AB - Gout is a metabolic disease, which is characterized by acute or chronic arthritis, and deposition of monosodium urate crystals in joint, bones, soft tissues, and kidneys. But large tophi are unusual in chronic gout. We report the case of a 67-year-oldArabman presenting chronic tophaceous gout with unusual large tophi involving multiple joints: hands, feet, elbows, and knees. Laboratory workup revealed elevated serum uric acid (96 mg/l, normal: 20-74 mg/l), with normal renal function test. In untreated patients, chronic tophaceous gout may develop, which is characterized by chronic destructive polyarticular involvement and tophi. The treatment consists to decrease serum uric acid level which eventually allows the regression of tophi. PMID- 26889314 TI - [Vulvo-clitoral elephantiasis: report of a new case]. PMID- 26889315 TI - [cutaneous leiomyoma: another cause of leg ulcers]. PMID- 26889316 TI - [Adrenal pheochromocytoma: diagnostic and therapeutic difficulties]. PMID- 26889317 TI - The status of medical laboratory towards of AFRO-WHO accreditation process in government and private health facilities in Addis Ababa, Ethiopia. AB - INTRODUCTION: The World Health Organization Regional Office for Africa (WHO AFRO) introduces a step wise incremental accreditation approach to improving quality of laboratory and it is a new initiative in Ethiopia and activities are performed for implementation of accreditation program. METHODS: Descriptive cross sectional study was conducted in 30 laboratory facilities including 6 laboratory sections to determine their status towards of accreditation using WHO AFRO accreditation checklist and 213 laboratory professionals were interviewed to assess their knowledge on quality system essentials and accreditation in Addis Ababa Ethiopia. RESULTS: Out of 30 laboratory facilities 1 private laboratory scored 156 (62%) points, which is the minimum required point for WHO accreditation and the least score was 32 (12.8%) points from government laboratory. The assessment finding from each section indicate that 2 Clinical chemistry (55.2% & 62.8%), 2 Hematology (55.2% & 62.8%), 2 Serology (55.2% & 62.8%), 2 Microbiology (55.2% & 62.4%), 1 Parasitology (62.8%) & 1 Urinalysis (61.6%) sections scored the minimum required point for WHO accreditation. The average score for government laboratories was 78.2 (31.2%) points, of these 6 laboratories were under accreditation process with 106.2 (42.5%) average score, while the private laboratories had 71.2 (28.5%) average score. Of 213 respondents 197 (92.5%) professionals had a knowledge on quality system essentials whereas 155 (72.8%) respondents on accreditation. CONCLUSION: Although majority of the laboratory professionals had knowledge on quality system and accreditation, laboratories professionals were not able to practice the quality system properly and most of the laboratories had poor status towards the WHO accreditation process. Thus government as well as stakeholders should integrate accreditation program into planning and health policy. PMID- 26889318 TI - [Serious materno-fetal alloimmunization: about a case and review of the literature]. PMID- 26889319 TI - Survival and determinants of mortality in adult HIV/Aids patients initiating antiretroviral therapy in Somali Region, Eastern Ethiopia. AB - INTRODUCTION: Studies have shown high initial mortality in Antiretroviral Therapy (ART) programs from resource-limited settings. However, there is dearth of evidence on treatment outcomes and associated determinant factors in public hospitals. Therefore, the objective of this study is to assess survival and identify predictors of death in adult HIV-infected patients initiating ART at a public hospital in Eastern Ethiopia. METHODS: A retrospective cohort study was conducted by reviewing baseline and follow-up records of patients who started ART between December 1, 2007 and December 31, 2011 at Kharamara hospital. Time to death was the main outcome measure. Kaplan-Meier models were used to estimate mortality and Cox proportional hazards models to identify predictors of mortality. RESULTS: A total of 784 patients (58.4% females) were followed for a median of 60 months. There were 87 (11.1%) deaths yielding an overall mortality rate of 5.15/100 PYO (95% CI: 4.73-6.37). The estimated mortality was 8.4%, 9.8%, 11.3%, 12.7% and 14.1% at 6, 12, 24, 36 and 48 months respectively. The independent predictors of death were single marital status (AHR: 2.31; 95%CI: 1.18-4.50), a bedridden functional status (AHR: 5.91; 95%CI: 2.87-12.16), advanced WHO stage (AHR: 7.36; 95%CI: 3.17-17.12), BMI < 18.5 Kg/m2 (AHR: 2.20; 95%CI: 1.18-4.09), CD4 count < 50 cells/uL (AHR: 2.70; 95%CI: 1.26-5.80), severe anemia (AHR: 4.57; 95%CI: 2.30-9.10), and TB co-infection (AHR: 2.30; 95%CI: 1.28 4.11). CONCLUSION: Improved survival was observed in patients taking ART in Somali region of Ethiopia. The risk for death was higher in patients with advanced WHO stage, low CD4 count, low Hgb, low BMI, and concomitant TB infection. Intensive case management is recommended for patients with the prognostic factors. Optimal immunologic and weight recoveries in the first 6 months suggest increased effort to retain patients in care at this period. PMID- 26889321 TI - Adenocarcinoma arising from chronic perianal crohn's disease: a case report. AB - Malignant transformation of perineal fistula in Crohn's disease has rarely been reported. We report a case of Crohn's disease with recurrent perineal fistulas. A 36-year-old male, diagnosed with Crohn's disease at the age of 24, developed adenocarcinoma in an anorectal fistula that had existed for years. He was treated with adjuvant chemoradiotherapy but died. A high index of suspicion and regular surveillance is recommended in chronic anorectal fistulas in Crohn's disease. The shorter duration of Crohn's fistulas prior to malignant degeneration necessitates an aggressive approach to rule out cancer. PMID- 26889322 TI - [Senior Loken syndrome]. PMID- 26889320 TI - Seven year review of retention in HIV care and treatment in federal medical centre Ido-Ekiti. AB - INTRODUCTION: Poor retention of patients in care is a major driver of poor performance and increased morbidity and mortality in HIV/AIDS programme despite the expansion and advancement Anti-retroviral Therapy (ART). The objective of this study is to assess retention rates and possible determining factors in People Living with HIV (PLHIV) on ART. METHODS: This is a descriptive, cross sectional study conducted in Federal Medical Center, Ido-Ekiti, Nigeria. Medical records of clients who were enrolled in ART Care and support unit (HIV Clinic) of the health facility from 2005 to 2012 were reviewed and analyzed using SPSS version 16. A total of 621 client records were reviewed for basic demographic information, CD4 count, WHO stage, number of follow-up visit, client ART status and client retention status (defined as client attending at least one clinic visit in 2012. RESULTS: A total of 347(63%) patients were retained in care and 208(37%) were not retained over the seven year review period. Retention was statistically significant with age (P-value 0.031), ART status (P-value 0.000) baseline CD4 (P-value 0.004), year of diagnosis and ART initiation (P-value= 0.027). Poor retention was associated decreasing age, pre-ART client, HIV stage 1&IV client and baseline CD4 above 400cell/mm(3). CONCLUSION: Retention in care of PLHIV is a minimum necessary condition for maintaining or restoring health in the long run. The strategies to sustain and improve retention rate should be adopted to maximize ART benefits. A follow-up study on other factors affecting retention from diagnosis to long term retention ART programme is recommended. PMID- 26889324 TI - Reexpansion pulmonary edema after drainage of tension pneumothorax. PMID- 26889323 TI - [Ischemic stroke in young patients: about 6 cases]. PMID- 26889325 TI - [Acute coronary syndrome following intravenous accidental injection with Bupivacaine]. PMID- 26889326 TI - [Laparoscopic resection of gastric duplication in adults: successful treatment for a rare disease]. PMID- 26889327 TI - [Predictive factors of TB treatment failure in Guinea Conakry]. PMID- 26889328 TI - [Visual ability to driving: example of candidates for the driving license in Libreville]. PMID- 26889329 TI - [Bone disease mimicking multiple myeloma in a octogenarian]. PMID- 26889330 TI - [A rare muscular complication of hemophilia: Myositis ossificans]. PMID- 26889331 TI - Intra and latero-sellar carotid aneurysm mimicking a pituitary adenoma. PMID- 26889332 TI - [Acute coronary syndrome: a mode of uncommon revelation of pheochromocytoma]. PMID- 26889333 TI - [Prevalence of hypertension in the population of the millers of the city of Lubumbashi, Democratic Republic of Congo]. PMID- 26889334 TI - [Non-Hodgkin lymphoma of the cavum: prognostic factors and therapeutic protocols]. PMID- 26889335 TI - [Purtscher retinopathy in Lupus]. PMID- 26889336 TI - [Upper gastrointestinal bleeding revealing a leech]. PMID- 26889338 TI - The "phantom" rash of Still's disease. PMID- 26889339 TI - Desmoid tumour: a rare etiology of intestinal obstruction. AB - Intestinal obstruction is a frequently encountered entity in surgical practice. The signs & symptoms, many a times, are suggestive of the level of obstruction, making the diagnosis of obstruction evident. There are various causes of intestinal obstruction which diversify to an enormous extent, stamping on the famous paradigm for the mysterious nature of the abdomen being referred to as the Pandora's Box. In accordance with the above saying, we report a rare case of a desmoid tumour, presenting as intestinal obstruction, which entices us to strongly believe the same. PMID- 26889340 TI - [Secondary chondrosarcoma of rare fibular location: report of a case]. PMID- 26889337 TI - An assessment of priority setting process and its implication on availability of emergency obstetric care services in Malindi District, Kenya. AB - INTRODUCTION: In spite of the critical role of Emergency Obstetric Care in treating complications arising from pregnancy and childbirth, very few facilities are equipped in Kenya to offer this service. In Malindi, availability of EmOC services does not meet the UN recommended levels of at least one comprehensive and four basic EmOC facilities per 500,000 populations. This study was conducted to assess priority setting process and its implication on availability, access and use of EmOC services at the district level. METHODS: A qualitative study was conducted both at health facility and community levels. Triangulation of data sources and methods was employed, where document reviews, in-depth interviews and focus group discussions were conducted with health personnel, facility committee members, stakeholders who offer and/ or support maternal health services and programmes; and the community members as end users. Data was thematically analysed. RESULTS: Limitations in the extent to which priorities in regard to maternal health services can be set at the district level were observed. The priority setting process was greatly restricted by guidelines and limited resources from the national level. Relevant stakeholders including community members are not involved in the priority setting process, thereby denying them the opportunity to contribute in the process. CONCLUSION: The findings illuminate that consideration of all local plans in national planning and budgeting as well as the involvement of all relevant stakeholders in the priority setting exercise is essential in order to achieve a consensus on the provision of emergency obstetric care services among other health service priorities. PMID- 26889341 TI - [Surgical treatment of palmar carpometacarpal dislocation: report of a case]. PMID- 26889343 TI - Mandibular Symphyseal/Parasymphyseal Fracture with Incisor Tooth Loss: Preventing Lower Arch Constriction. AB - Mandibular fractures are the second most common fractures of the face after the nasal bone. Mandibular symphyseal/parasymphyseal fracture comprises 15.6 to 29.3% of mandibular fractures. Tooth loss in the fracture line is a known phenomenon, but space loss has not been evaluated comprehensively in the literature. In a retrospective study, patients with mandibular symphyseal/parasymphyseal fractures, who had been treated from 2012 to 2013 in Mashhad University, Iran, Emdadi Hospital, were recalled. Patients with mandibular incisor tooth/teeth loss were included in the study. Space loss, the technique used to replace the lost tooth/teeth, upper and lower dental midline relationship, combination fracture or fractures in other facial skeleton, and type of treatment were evaluated. Of 98 patients with mandibular symphyseal/parasymphyseal fractures, 22.5% had incisor tooth/teeth loss. In this group, 73% had space loss. Only four patients had replaced the lost tooth/teeth. Dental midlines did not match each other in patients whose feature was evaluated. Open reduction and internal fixation with miniplates were used in symphyseal/parasymphyseal fractures except one. Space loss after mandibular symphyseal/parasymphyseal fracture with incisor tooth loss is a common error. The most important factor to prevent complications related to space loss following mandibular symphyseal/parasymphyseal fracture accompanying incisor tooth loss is space preservation. PMID- 26889342 TI - Bioactive-glass in Oral and Maxillofacial Surgery. AB - The use of synthetic materials to repair craniofacial defects is increasing today and will increase further in the future. Because of the complexity of the anatomy in the head and neck region, reconstruction and augmentation of this area pose a challenge to the surgeon. This review discusses key facts and applications of traditional reconstruction bone substitutes, also offering comparative information. It then describes the properties and clinical applications of bioactive-glass (B-G) and its variants in oral and maxillofacial surgery, and provides clinical findings. The discussion of each compound includes a description of its composition and structure, the advantages and shortcomings of the material, and its current uses in the field of osteoplastic and reconstructive surgery. With a better understanding of the available alloplastic implants, the surgeon can make a more informed decision as to which implant would be most suitable in a particular patient. PMID- 26889344 TI - The Role of a Conservative Minimal Interventional Management Protocol in the Fractures of the Dentate Portion of the Adult Mandible. AB - Mandibular fractures are commonly encountered by the maxillofacial surgeon. Maxillomandibular fixation (MMF) and open reduction and internal fixation (ORIF), or a combination of both, are the accepted standard treatments. This study aims to assess the role of a conservative minimal intervention protocol in the management of undisplaced/minimally displaced fractures of the dentate portion of the adult mandible and the complications associated with such minimalistic intervention. Thirty-four patients with undisplaced/minimally displaced fractures of the dentate portion of the adult mandible were advised to restrict mouth opening and limit themselves to a soft diet for a minimum of 4 weeks. All patients were advised follow-up at regular intervals for at least 3 months. Five patients were lost to follow-up. Symphysis and parasymphysis fractures were the most common fracture locations. Fourteen patients needed tension band stabilization with a mandibular arch bar/bridle wiring and three patients required extraction of luxated teeth. All patients showed satisfactory healing except three in whom additional intervention (ORIF) was performed. The improvement in mouth opening was statistically significant. Complications were seen more frequently among smokers and alcoholics. For patients with minimally displaced mandibular fractures, it is necessary to consider if the perceived benefits of intervention justify the associated added costs and possible complications. Patients have to be fully informed about the possible complications while using this minimal intervention protocol. This study concludes that a conservative minimal intervention management protocol for such fractures of the dentate portion of the mandible can produce satisfactory results. PMID- 26889346 TI - Patterns of Intracranial Hemorrhage in Pediatric Patients with Facial Fractures. AB - Intracranial hemorrhage (ICH) is a potentially fatal injury accompanying fractures of the cranium and facial skeleton. When occurring at a young age, ICH can lead to developmental delay, cerebral palsy, epilepsy, and death. It is therefore important for clinicians to recognize the presence of ICH early, and understand the factors that affect its prognosis. In this study, we aim to identify diagnostic and prognostic signs for ICH in pediatric facial fracture patients by examining aspects of patient presentation, concomitant injuries, and fracture patterns. Data were collected for all radiologically diagnosed facial fractures between January 2000 and December 2012 at a level I trauma center in Newark, NJ. This was then further refined to include only patients 18 years of age or younger who had a documented ICH. Patient age, Glasgow coma scale (GCS) on presentation, fracture location, type of hemorrhage, and certain aspects of management were collected from these records. Data were then analyzed by either Pearson chi-square test or a t-test to determine significant relationships. A total of 285 pediatric patients were found to have sustained a facial fracture during this time period, 67 of which had concomitant ICH; 46 of these patients were male and 21 were female, with average ages of 14.26 and 9.52 (p < 0.01), respectively. Causes of injury included motor vehicle accidents, pedestrians struck, assault, falls, gunshot injuries, and sports-related injuries. All patients who suffered injuries as a result of violent crimes (assault and gunshot injuries) were male. Although nearly all fracture patterns were significantly associated with the presence of ICH, mandibular fractures showed a significant negative association with the presence of ICH. In addition, patients who received surgical intervention were significantly younger than those who did not (7.7 vs. 13.7, p < 0.05). The GCS was significantly lower in patients who underwent ICP (intracranial pressure) monitoring or EVD (external ventricular drain) placement, suffered intraventricular hemorrhage, experienced worsening of hemorrhage on repeat imaging, and suffered fatal injuries. Our data also showed a significant association between the need for intubation in the emergency department and fatality. Because the consequence of ICH can be life threatening, proper diagnosis and management are imperative. The purpose of this study is to describe patterns associated with ICH in pediatric facial fracture patients to promote early recognition of the injury and understanding of poor prognostic signs. PMID- 26889345 TI - Modified Transconjunctival Approach to the Lower Eyelid: Technical Details for Predictable Results. AB - The transconjunctival approach to the lower orbit is well described in the literature and has been used for both cosmetic and reconstructive purposes. When properly performed, it allows access to the orbital floor and inferior orbital rim with minimal lower lid morbidity and an inconspicuous scar. Many variations of this approach have been described and these can lead to confusion and uncertainty regarding the surgical technique including when and how to best utilize this approach in the traumatized eyelid. Residents and less experienced attendings employing this approach often fail to fully understand the technical and anatomic details that can make this a very fast and simple way to gain complete access to the inferior, medial, and lateral orbit while minimizing complications such as postoperative lid malposition and canthal deformities. We describe our method for transconjunctival access to the inferior orbital rim and orbital floor with specific attention to several precise surgical aspects that make this a fast and reliable technique with low morbidity and predictable architecture of closure. PMID- 26889348 TI - Transcaruncular Approach for Treatment of Medial Wall and Large Orbital Blowout Fractures. AB - We evaluate the safety and efficacy of the transcaruncular approach for reconstruction of medial orbital wall fractures and the combined transcaruncular transconjunctival approach for reconstruction of large orbital defects involving the medial wall and floor. A retrospective review of the clinical and radiographic data of patients who underwent either a transcaruncular or a combined transcaruncular-transconjunctival approach by a single surgeon for orbital fractures between June 2007 and June 2013 was undertaken. Seven patients with isolated medial wall fractures underwent a transcaruncular approach, and nine patients with combined medial wall and floor fractures underwent a transcaruncular-transconjunctival approach with a lateral canthotomy. Reconstruction was performed using a porous polyethylene implant. All patients with isolated medial wall fractures presented with enophthalmos. In the combined medial wall and floor group, five out of eight patients had enophthalmos with two also demonstrating hypoglobus. The size of the medial wall defect on preoperative computed tomography (CT) scan ranged from 2.6 to 4.6 cm(2); the defect size of combined medial wall and floor fractures was 4.5 to 12.7 cm(2). Of the 11 patients in whom postoperative CT scans were obtained, all were noted to have acceptable placement of the implant. All patients had correction of enophthalmos and hypoglobus. One complication was noted, with a retrobulbar hematoma having developed 2 days postoperatively. The transcaruncular approach is a safe and effective method for reconstruction of medial orbital floor fractures. Even large fractures involving the orbital medial wall and floor can be adequately exposed and reconstructed with a combined transcaruncular-transconjunctival-lateral canthotomy approach. The level of evidence of this study is IV (case series with pre/posttest). PMID- 26889347 TI - Reconstructive Indications of Anterolateral Thigh Free Flaps in Head and Neck Reconstruction. AB - Anterolateral thigh (ALT) free flap is a common flap with multitude of indications. The purpose of this article is to review the reconstructive indications of the flap in head and neck defects. This is a retrospective study of 194 consecutive ALT flaps. Data including patient characteristics (age, sex, comorbidities), disease characteristics (histology, T stage), and flap characteristics (size of the flap, type of closure of ALT donor site) were collected. The outcome in terms of flap success rate, surgical, and donor site morbidity were studied. A total of 194 flaps were performed in 193 patients over a period of 10 years. Mean age of the patients was 55 years (range 16-80 years). Out of the 193 patients, 91 (47.1%) patients had oromandibular defects, 52 (26.9%) had tongue defects, 15 (7.7%) had pharyngeal defects, 17 (8.8%) had skull base defects, 4 (2%) had scalp defects, and 14 (7.2%) had contour defects of the neck. The overall flap success rate was 95.8% (8 total flap loss out of 194). Hypertrophic scar was the commonest donor site problem seen in 20 (10.3%) patients. This study shows the versatility of free ALT flap in head and neck reconstruction. It is a reliable and safe. Donor site morbidity is minimal. PMID- 26889349 TI - Orbital Wall Reconstruction with Two-Piece Puzzle 3D Printed Implants: Technical Note. AB - The purpose of this article is to describe a technique for secondary reconstruction of traumatic orbital wall defects using titanium implants that act as three-dimensional (3D) puzzle pieces. We present three cases of large defect reconstruction using implants produced by Xilloc Medical B.V. (Maastricht, the Netherlands) with a 3D printer manufactured by LayerWise (3D Systems; Heverlee, Belgium), and designed using the biomedical engineering software programs ProPlan and 3-Matic (Materialise, Heverlee, Belgium). The smaller size of the implants allowed sequential implantation for the reconstruction of extensive two-wall defects via a limited transconjunctival incision. The precise fit of the implants with regard to the surrounding ledges and each other was confirmed by intraoperative 3D imaging (Mobile C-arm Systems B.V. Pulsera, Philips Medical Systems, Eindhoven, the Netherlands). The patients showed near-complete restoration of orbital volume and ocular motility. However, challenges remain, including traumatic fat atrophy and fibrosis. PMID- 26889350 TI - Assessment of Bite Force in Patients Treated with 2.0-mm Traditional Miniplates versus 2.0-mm Locking Plates for Mandibular Fracture. AB - The objective of this study is to analyze the difference in bite forces in patients treated for mandibular fractures with 2.0 mm conventional and locking titanium plating system. A randomized study was performed for the treatment of fractures of mandible. In this study, 20 adult patients with isolated mandibular fracture were included. The patients were randomly allocated into two groups, that is, Group I-2.0 mm nonlocking (traditional) and Group II-2.0 mm locking plates. Bite force was evaluated at 1st, 3rd, and 6th weeks. Comparison of all the assessed parameters between both the groups depicted no significant difference in terms of pain, swelling including the incidence of infection, paresthesia, and hardware failure. Although same was true in case of bite force between both the groups at various time intervals, there was statistically significant increase in the bite force within the group comprising patients in whom locking plates was used between 1st and 3rd weeks follow-up period and highly significant increase in bite force between 1st and 6th weeks of follow-up period. The rapid improvement of bite force values when locking plates were used implies that the locking plate can be used in preference to conventional plates to achieve early mobilization with assured stability in the treatment of mandibular fractures. PMID- 26889351 TI - Assessment of Mandibular Distraction Regenerate Using Ultrasonography and Cone Beam Computed Tomography: A Clinical Study. AB - Distraction osteogenesis (DO) is becoming a popular method of reconstruction for maxillofacial bony deformities or defects secondary to trauma or surgical tumor ablation. However, the technique is very sensitive in terms of the rate and rhythm of distraction. Because of this, there is a need for monitoring of the distraction regenerate during the distraction as well as the consolidation period. The present study was conducted to assess the regenerate using two imaging modalities, namely, ultrasonography (USG) and cone beam computed tomography (CBCT) to determine their relative efficacies and to weigh their clinical usefulness in assessment of DO regenerate. The study was conducted on 12 patients (18 sites) who underwent mandibular distraction for correction of facial deformities. The results showed that overall USG correlated better with the condition of regenerate (r = 0.606) as compared with CBCT (r = 0.476). However, USG was less effective as compared with CBCT in assessing the regenerate once corticomedullary differentiation occurred in the bone. PMID- 26889352 TI - Opportunity Cost of Surgical Management of Craniomaxillofacial Trauma. AB - The provision of trauma care is a financial burden, continually associated with low reimbursement, and shifts the economic burden to major trauma centers and providers. Meanwhile, the volume of craniomaxillofacial (CMF) trauma and the number of surgically managed facial fractures are unchanged. Past financial analyses of cost and reimbursement for facial trauma are limited to mandibular and midface injuries, consistently revealing low reimbursement. The incurred financial burden also coincides with the changing landscape of health insurance. The goal of this study is to determine the opportunity cost of operative management of facial trauma at our institution. From our CMF database of greater than 3,000 facial fractures, the physician charges, collections, and relative value units (RVUs) for CMF trauma per year from 2007 to 2013 were compared with a general plastic surgery and otolaryngology population undergoing operative management during this same period. Collection rates were analyzed to assess if a significant difference exists between reimbursement for CMF and non-CMF cases. Results revealed a significant difference between the professional collection rate for operative CMF trauma and that for other operative procedures (17.25 vs. 29.61%, respectively; p < 0.0001). The average number of RVUs billed per provider for CMF trauma declines significantly, from greater than 700 RVUs to 300 over the study period, despite a stable volume. Surgical management of CMF trauma generates an unfavorable financial environment. The large opportunity cost associated with offering this service is a potential threat to the sustainability of providing care for this population. PMID- 26889353 TI - Custom Anatomical 3D Spacer for Temporomandibular Joint Resection and Reconstruction. AB - Two cases are presented using a two-stage approach and a custom antibiotic spacer placement. Temporomandibular reconstruction can be very demanding and accomplished with a variety of methods in preparation of a total joint and ramus reconstruction with total joint prostheses (TMJ Concepts, Ventura, CA). Three dimensional reconstructions from diagnostic computed tomography were used to establish a virtually planned resection which included the entire condyle-ramus complex. From these data, digital designs were used to manufacture molds to facilitate intraoperative fabrication of precise custom anatomic spacers from rapidly setting antibiotic-impregnated polymethyl methacrylate. Molds were manufactured using vat polymerization (stereolithography) with a photopolymer in the first case and powder bed fusion (electron beam melting) with Ti6AL4V for the second. Surgical methodology and the use of molds for intraoperative spacer fabrication for each case are discussed. PMID- 26889354 TI - Guided Bone Regeneration of an Atrophic Mandible with a Heterologous Bone Block. AB - The aim of this work was to test the effectiveness of using enzymatically deantigenated equine bone block as a scaffold for guided bone regeneration (GBR) during a horizontal augmentation of the lower jaw. A partially edentulous atrophic mandible was augmented using an equine-derived block with an expanded polytetrafluoroethylene membrane. After 8.5 months, two bone core samples were collected at the augmentation site, and implants were placed. A definitive prosthesis delivered 6 months after implant placement provided excellent functional and aesthetic rehabilitation throughout the follow-up period. Histological and histomorphometrical analysis of the biopsies showed newly formed bone to be present and the residual biomaterial was still undergoing remodeling. Comparison of cone beam computed tomography scans taken before augmentation and 26 months later showed maintenance of ridge width and possible corticalization of the vestibular augmented ridge side. The equine-derived bone block placed in accordance with GBR principles provided a successful clinical, radiographic, and histological outcome. PMID- 26889356 TI - Effect of Temperature, Concentration and Contact Time of Sodium Hypochlorite on the Treatment and Revitalization of Oral Biofilms. AB - Background and aims. Increasing the temperature of sodium hypochlorite (NaOCl) enhances its dissolution and antibacterial properties. However, the high resistance of multi-species biofilms could restrict the effect of the solution regardless of its temperature, enabling the long-term recovery of the surviving bacteria. The aim of this study was to investigate if the increase of temperature of NaOCl improves its antibacterial and dissolution ability on oral biofilms and if the post-treatment remaining bacteria were capable of growing in a nutrient rich medium. Materials and methods. Forty dentin blocks were infected intra orally for 48 hours. Then, the specimens were treated with 1% and 2.5% NaOCl at room temperature (22oC) and body temperature (37oC) for 5 and 20 min. The percentage of live cells and the biovolume were measured pre- (control) and post treatment and after the biofilm revitalization. Four confocal 'stacks' were chosen from random areas of each sample. Statistical analysis was performed using Kruskal-Wallis and Dunn tests. Statistical significance was defined at P <0.05. Results. All the NaOCl groups were effective in dissolving the biofilm at any temperature, concentration and contact time without statistical differences among them (P >0.05). The 1%-NaOCl for 5min was not able to significantly kill the bacteria, regardless of its temperature and contact time (P >0.05). Conclusion. The temperature variation of the NaOCl was not relevant in killing or dissolving bacterial biofilms. Twenty-four hours of reactivation did not appear to be enough time to induce a significant bacterial growth. PMID- 26889357 TI - Comparative Evaluation of the Effect of Manufacturing Process on Distortion of Rotary ProFile and Twisted File: An in Vitro SEM Study. AB - Background and aims. The manufacturing process of rotary Ni-Ti file can influence its resistance to fracture. The rotary ProFile (Dentsply-Maillefer, Baillagues, Switzerland) is manufactured by grinding mechanism whereas Twisted File (Sy-bron Endo, USA) is manufactured with a twisting method. The purpose of this study was to comparatively evaluate the effect of manufacturing process on distortion of rotary ProFile and Twisted files using scanning electron microscopy after in vitro use. Materials and methods. Five sets of each type of file were used for this study -rotary ProFile (group A) and Twisted file (group B). Each set was used according to manufacturer's instructions to prepare 5 mesial canals of extracted mandibular molars. The changes in files were observed under a scanning electron microscope at *18, *100, *250 and *500 magnifications. Observations were classified as intact with no discernible distortion, intact but with unwinding, and fractured. Group A and B were then compared for deformation and fracture using two-proportion z-test. Results. On SEM observation, used rotary ProFile showed microfractures along the machining grooves whereas Twisted file showed crack propagation that was perpendicular to the machining marks. On statistical analysis, no significant difference was found between ProFile and Twisted file for deformation (P=0.642) and fracture (P=0.475). Conclusion. Within the experimental protocol of this study, it was concluded that both ProFile and Twisted files exhibited visible sign of distortion before fracture. But Twisted file gained edge over ProFile because of its manufacture design and unparalleled resistance to breakage. PMID- 26889355 TI - Nevoid Basal Cell Carcinoma Syndrome: A Long-Term Study in a Family. AB - We present a family case series with 10 individuals having nevoid basal cell carcinoma syndrome (NBCCS) with a 10-year follow-up. All articles published in the literature between 1967 and 2011 on familial Gorlin-Goltz syndrome in any language were surveyed to determine the mapping of cases per country of occurrence of this disease. All patients in the present series were presented with calcification of the falx cerebri, mild hypertelorism, and frontal bossing. Odontogenic keratocystic tumors, palmar and plantar pits, and multiple basal cell carcinomas occurred in 90, 40, and 20%, respectively, of the patients. One of the patients died of skin cancer. Diagnosis of odontogenic keratocyst tumors was confirmed by histopathological examination. NBCCS is a rare autosomal dominant cancer predisposition syndrome; it is important to recognize it when a patient has multiple odontogenic keratocyst tumors because life-long monitoring is essential for patient management. PMID- 26889358 TI - Comparison of Push-out Bond Strength of Gutta-percha to Root Canal Dentin in Single-cone and Cold Lateral Compaction Techniques with AH Plus Sealer in Mandibular Premolars. AB - Background and aims. The single-cone technique has gained some popularity in some European countries. The aim of the present study was to compare the push-out bond strength of gutta-percha to root canal dentin with the single-cone and cold lateral compaction canal obturation techniques. Materials and methods . The root canals of 58 human mandibular premolars were prepared using modified crown-down technique with ProTaper rotary files up to #F3as a master apical file (MAF) and divided randomly into groups A and B based on canal obturation technique. In group A (n = 29) the root canals were obturated with single-cone technique with #F3(30/.09) ProTaper gutta-percha, which was matched with MAF in relation to diameter, taper and manufacturer; in group B (n = 29) the canals were obturated with gutta-percha using cold lateral compaction technique. In both groups AH plus sealer were used. After two weeks of incubation, three 2-mm slices were prepared at a distance of 2 mm from the coronal surface and push-out test was carried out. Data were analyzed with descriptive statistics using independent samples t-test. Results. There were statistically significant differences between two groups. The mean push-out bond strength was higher in group B (lateral compaction technique) compared to group A (single-cone technique; P < 0.05). Conclusion . Use of single cone technique for obturation of root canals resulted in a lower bond strength compared to cold lateral compaction technique. PMID- 26889359 TI - Evaluation of Polymerization Efficacy in Composite Resins via FT-IR Spectroscopy and Vickers Microhardness Test. AB - Background and aims. Polymerization efficacy affects the properties and performance of composite resin restorations.The purpose of this study was to evaluate the effectiveness of polymerization of two micro-hybrid, two nano-hybrid and one nano-filled ormocer-based composite resins, cured by two different light curing systems, using Fourier transformation infrared (FT-IR) spectroscopy and Vickers microhardness testing at two different depths (top surface, 2 mm). Materials and methods. For FT-IR spectrometry, five cylindrical specimens (5mm in diameter * 2 mm in length) were prepared from each composite resin using Teflon molds and polymerized for 20 seconds. Then, 70-MUm wafers were sectioned at the top surface and at2mm from the top surface. The degree of conversion for each sample was calculated using FT-IR spectroscopy. For Vickers micro-hardness testing, three cylindrical specimens were prepared from each composite resin and polymerized for 20 seconds. The Vickers microhardness test (Shimadzu, Type M, Japan) was performed at the top and bottom (depth=2 mm) surfaces of each specimen. Three-way ANOVA with independent variables and Tukey tests were performed at 95% significance level. Results. No significant differences were detected in degree of conversion and microhardness between LED and QTH light curing units except for the ormocer-based specimen, CeramX, which exhibited significantly higher DC by LED. All the composite resins showed a significantly higher degree of conversion at the surface. Microhardness was not significantly affected by depth, except for Herculite XRV Ultra and CeramX, which showed higher values at the surface. Conclusion. Composite resins containing nano-particles generally exhibited more variations in degree of conversion and microhardness. PMID- 26889360 TI - Effect of Resin Cement Pre-heating on the Push-out Bond Strength of Fiber Post to Root Canal Dentin. AB - Background and aims. Various factors influence the interfacial bond between the fiber posts and root canal dentin. The aim of the present study was to evaluate the effect of pre-warming of resin cement on the push-out bond strength of fiber posts to various segments of root canal dentin. Materials and methods . In this in vitro study, 40 single-rooted human premolars were decoronated and underwent root canal treatment along with post space preparation. The samples were randomly divided into two groups: In group 1, Panavia F 2.0 cement was used at room temperature; in group 2, the same cement was warmed to 55-60 degrees C before mixing. After fiber posts were placed and cemented in the root canals, 3 dentin/post sections (coronal, middle and apical) with a thickness of 3 mm were prepared. A universal testing machine was used to measure push-out bond strength in MPa. Data was analyzed using two-factor ANOVA and a post hoc Tukey test at alpha=0.05. Results. The mean value of push-out bond strength was high at room temperature, and the differences in the means of push-out bond strength values between the resin cement temperatures and between different root segments in each temperature were significant (P<0.05). Conclusion. Pre-warming of Panavia F 2.0 resin cement up to 55-60 degrees C reduced push-out bond strength to root canal dentin. In addition, in each temperature group bond strengths decreased from coronal to apical segments. PMID- 26889361 TI - Effects of Treatment with Various Remineralizing Agents on the Microhardness of Demineralized Enamel Surface. AB - Background and aims. Remineralization of incipient caries is one of the goals in dental health care. The present study aimed at comparing the effects of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP), Remin Pro((r)), and 5% sodium fluoride varnish on remineralization of enamel lesions. Materials and methods. In this in vitro study, 60 enamel samples were randomly allocated to six groups of 10. After four days of immersion in demineralizing solution, microhardness of all samples was measured. Afterward, groups 1-3 underwent one time treatment with fluoride varnish, CPP-ACP, and Remin Pro((r)), respectively. Microhardness of groups 4-6 was measured not only after one-month treatment with the above-mentioned materials (for eight hours a day), but also after re-exposing to the demineralizing solution. The results were analyzed by one-way analysis of variance (ANOVA), repeated measures ANOVA, and Fisher's least significant difference (LSD) test. Results . None of the regimens could increase microhardness in groups 1-3. However, one-month treatment regimens in groups 4-6 caused a significant increase in microhardness. The greatest microhardness was detected in the group treated with CPP-ACP (P = 0.001). In addition, although microhardness reduced following re-demineralization in all three groups, the mean reduction was minimum in the CPP-ACP-treated group (P < 0.001). Conclusion. While long-term repeated application of all compounds improved microhardness, the remineralization potential of CPP-ACP was significantly higher than that of Remin Pro((r)) and sodium fluoride varnish. PMID- 26889363 TI - Evaluation of Force Degradation Pattern of Elastomeric Ligatures and Elastomeric Separators in Active Tieback State. AB - Background and aims. The purpose of this study was to evaluate initial force and force decay of commercially available elastomeric ligatures and elastomeric separators in active tieback state in a simulated oral environment. Materials and methods. A total of 288 elastomeric ligatures and elastomeric separators from three manufacturers (Dentaurum, RMO, 3M Unitek) were stretched to 100% and 150% of their original inner diameter. Force levels were measured initially and at 3 minute, 24-hour, and 1-, 2-, 3- and 4-week intervals. Data were analyzed by univariate analysis of variance and a post hoc Tukey test. Results. The means of initial forces of elastomeric ligatures and separators from three above-mentioned companies, when stretched to 100% of their inner diameters, were 199, 305 and 284 g, and 330, 416, 330 g; when they were stretched to 150% of their inner diameters the values were 286, 422 and 375 g, and 433, 540 and 504 g, respectively. In active tieback state, 11-18% of the initial force of the specimens was lost within the first 3 minutes and 29-63% of the force decay occurred in the first 24 hours; then force decay rate decreased. 62-81% of the initial force was lost in 4 weeks. Although force decay pattern was identical in all the products, the initial force and force decay of Dentaurum elastomeric products were less than the similar products of other companies (P<0.05). Under the same conditions, the force of elastomeric separators was greater than elastomeric ligatures of the same company. Conclusion. Regarding the force pattern of elastomeric ligatures and separators and optimal force for tooth movement, many of these products can be selected for applying orthodontic forces in active tieback state. PMID- 26889362 TI - The Comparison of Stress Distribution with Different Implant Numbers and Inclination Angles In All-on-four and Conventional Methods in Maxilla: A Finite Element Analysis. AB - Background and aims. All-on-four technique involves the use of tilted implants to allow for shorter cantilevers. This finite element analysis aimed at investigating the amount and distribution of stress in maxillary bone surrounding the implants with all-on-four vs. frequently used method with six implants technique using different numbers and inclination angles. Materials and methods. A 3D edentulous maxillary model was created and implants were virtually placed anterior to the maxillary sinus and splinted with a superstructure. In total, five models were designed. In the first to the fourth models, four implants were placed with distal implants inclined 0, 15, 30, and 45 degrees, respectively. In the fifth model, six vertical implants were placed. 100 N loading was placed in the left most distal region of the superstructure. Maximum von Mises stress values were evaluated in cancellous and cortical bone. Results. The maximum stress values recorded in cancellous and cortical bone were 7.15 MPa and 51.69 MPa, respectively (model I). The reduction in stress values in models II to V 6%, 18%, 54%, and 24% in cancellous bone and 12%, 36%,62%, and 62% in cortical bone, respectively. Conclusion. Increasing the inclination in posterior implants resulted in reduction of cantilever length and maximum stress decline in both cancellous and cortical bone. The effect of cantilever length seems to be a dominant factor which can diminish stress even with less number of implants. PMID- 26889364 TI - Evaluation of the Relationship between Serum Lipid Profile andOral Lichen Planus. AB - Background and aims. Oral lichen planus (OLP) is an immunologic disorder. A large number of studies have reported that lipid rafts have a key role in receptor signaling of lymphocytes. Here, we explore the potential of lipid rafts as targets for the development of a new class of agents to down-modulate immune responses and treat autoimmune diseases. Materials and methods. The present cross sectional study evaluated 88 patients referring to the Department of Oral Medicine in 3 groups (Group 1: erosive OLP; Group 2: non-erosive OLP; Group 3: healthy). A total of 3 mL of blood sample was taken from each subject and the serum levels of cholesterol, triglycerides, HDL and LDL were determined. The mean outcomes of each group were compared with each other and analyzed two by two. Results. The results of statistical analyses showed no significant differences in mean HDL and LDL serum levels between the three groups. The results of post hoc LSD test showed that mean serum levels of subjects with erosive and non-erosive lichen planus were higher than those in healthy subjects. In relation to triglyceride serum levels, the mean serum levels of triglycerides were higher in erosive and non-erosive OLP patients compared to healthy subjects. Conclusion. Triglyceride and cholesterol can be considered to have a critical role in the incidence of lichen planus and in its manifestations as predisposing factors. PMID- 26889365 TI - Garlic ((Allium sativum)) Fresh Juice Induces Apoptosis in Human Oral Squamous Cell Carcinoma: The Involvement of Caspase-3, Bax and Bcl-2. AB - Background and aims. There is no report on the apoptotic impact of Allium sativum L.(Garlic) on the oral squamous cell carcinoma (KB); hence, this study was designed to survey the apoptotic effects of garlic fresh juice (GFJ) on the KB cells. Materials and methods. MTTassay (MicrocultureTetrazolium Assay) was carried out to evaluate the cytotoxicity of GFJ on KB cells. Furthermore, TUNEL(Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling)and DNA fragmentation tests were performed to determine if GFJ is able to induce apoptosis in KB cells. Also a standard kit was used to assess caspase-3 activity in KB cells. Also western blotting was employed to evaluate the effect of GFJ on Bax:Bcl-2 ratio. Results. Significant cytotoxic effects were observed for the minimum used concentration (1MUg/mL) as calculated to be 77.97+/-2.3% for 24 h and 818+/-3.1% for 36h of incubation (P < 0.001). Furthermore, TUNEL and DNA fragmentation tests corroborated the apoptosis inducing activity of GFJ. Consistently, after treating KB cells with GFJ(1MUg/mL), caspase-3 activity and Bax:Bcl-2 ratio were raised by 7.3+/-0.6 and (P <0.001) folds, respectively. Conclusion. The results of this study advanced that GFJ induces apoptosis in the KB cells through increasing caspase-3 activity and Bax:Bcl2 ratio which could be attributed to its organo-sulfurcomponents. PMID- 26889366 TI - Candida Carriage Rate and Growth Characteristics of Saliva in Diabetes Mellitus Patients: A Case-Control Study. AB - Background and aims. The aim of this study was to establish a relationship between salivary glucose levels and Candida carriage rate in type 2 diabetes mellitus patients and assess the growth characteristics and acid production of Candida in glucose-supplemented saliva. Materials and methods . A total of 90 subjects, 30 with controlled type 2 diabetes, 30 with uncontrolled type 2 diabetes and 30 without diabetes (control subjects), aged 30-60 years, participated in the study. Unstimulated saliva was collected and investigated for glucose levels (GOD-POD method), colony-forming units (CFU) of Candida and salivary pH, using Indikrom paper strips). Analysis of statistical significance of salivary glucose and PH levels was carried out using post hoc Tukey HSD test. Correlation of Candida carriage rate with salivary glucose and salivary PH in the study groups and control group was made using Pearson's correlation. Results. Candida CFUs were significantly higher in diabetic subjects, with a significant and positive correlation with salivary glucose levels. There was a negative correlation between salivary PH levels and Candida carriage rate. Conclusion. Increased salivary glucose was associated with increased prevalence of oral Candida in diabetic subjects. The growth of Candida in saliva was accompanied by a rapid decline in PH, which in turn favored their growth. PMID- 26889367 TI - Effect of Cigarette Smoke on Salivary Total Antioxidant Capacity. AB - Background and aims. Cigarette smoke can induce oral cancer by its free radicals and oxidative damage. Salivary anti-oxidants system is believed to have an important role in defense mechanisms against oxidative stress. This study was compared total antioxidant capacity (TAoC) of saliva in smokers and nonsmokers. Materials and methods . In this cross-sectional study, 30 male smokers with mean age of 45.23 years and 30 nonsmokers with mean age of 45.30 years participated. Unstimulated whole saliva samples were collected in the morning in two groups by spitting method. TAoC of saliva was measured with the special kit in two groups at the same time. Statistical analysis was performed by covariance test. Results. The mean salivary TAoC in nonsmokers (0.741+/-0.123 U/ml) was higher than that in smokers (0.529+/-0.167 U/ml). This difference was statistically significant (P<0.001). Conclusion. Smoking can alter salivary antioxidant capacity. PMID- 26889368 TI - Variations in Practice to Therapeutic Monitoring of Tacrolimus following Primary Adult Liver Transplantation. AB - BACKGROUND: There is limited clinical evidence evaluating the correlation between immunosuppressant monitoring practice and transplant outcomes. OBJECTIVE: To assess current practice of tacrolimus trough monitoring in early post-operative period following liver transplantation (LT), and its impact on outcomes. METHODS: The duration to trough levels (DTT) were calculated in patients undergoing primary LT. The impact of variability in DTT on graft rejection episodes, serum tacrolimus level and renal function was assessed. These results were converted into a drug level estimation tool, which was validated in a prospective cohort of patients. RESULTS: 2946 events in 274 patients were evaluated. The median DTT was 7:19 hrs (range: 27 min to 19:38 hrs). In 72% (2140 events) of the occasions, DTT was <8 hrs. There was a significant (p=0.022) correlation between DTT and tacrolimus level. Despite clinical decisions were taken to modify the dose of tacrolimus based on trough level, neither did DTT affect the average creatinine levels (p=0.923), nor the variability in DTT did affect acute rejection (p=0.914, and 0.712, respectively). A dose estimation tool was developed and applied to validation cohort (n=612), and returned a moderate R(2) value of 0.50. CONCLUSION: There is a significant variation in the "real world" monitoring of tacrolimus with DTT in majority of measurements falling below recommendations; reassuringly, this did not lead to adverse transplant sequelae. PMID- 26889369 TI - Histopathological Comparison between Bone Marrow- and Periodontium-derived Stem Cells for Bone Regeneration in Rabbit Calvaria. AB - BACKGROUND: Periodontitis is an important oral disease. Stem cell therapy has found its way in treatment of many diseases. OBJECTIVE: To evaluate the regenerative potential of periodontal ligament-derived stem cells (PDLSCs) and osteoblast differentiated from PDLSC in comparison with bone marrow-derived mesenchymal stem cells (BM-MSCs) and pre-osteoblasts in calvarial defects. METHODS: After proving the existence of surface markers by flow cytometry, BM MSCs were differentiated into osteoblasts. 5 defects were made on rabbit calvaria. 3 of them were first covered with collagen membrane and then with BM MSCs, PDLSCs, and pre-osteoblasts. The 4(th) defect was filled with collagen membrane and the 5(th) one was served as control. After 4 weeks, histological (quantitative) and histomorphological (qualitative) surveys were performed. RESULTS: Both cell lineages were positive for CD-90 cell marker, which was specifically related to stem cells. Alizarin red staining was done for showing mineral material. RT-PCR set up for the expression of Cbfa1 gene, BMP4 gene, and PGLAP gene, confirmed osteoblast differentiation. The findings indicated that although PDLSCs and pre-osteoblasts could be used for bone regeneration, the rate of regeneration in BM-MSCs-treated cavities was more significant (p<0.0001). CONCLUSION: The obtained results are probably attributable to the effective micro environmental signals caused by different bone types and the rate of cell maturation. PMID- 26889371 TI - Knowledge, Attitude and Practice Regarding Organ Donation among Indian Dental Students. AB - BACKGROUND: Of the overall 9.5 million deaths annually in India, nearly 100,000 are due to organ failure. To save and extend lives, organ donation and organ transplantation have become the only hope. Health care professionals (HCPs) are a key element in facilitating cadaveric organ donation process. OBJECTIVE: To assess and compare the knowledge, attitude, and practice regarding organ donation among undergraduate dental students. METHODS: A cross-sectional study was conducted among 298 undergraduate dental students of the Panineeya Institute of Dental Sciences and Hospital, Hyderabad, India. A 27-item self-administered questionnaire, which assessed the levels of knowledge (Q1-13), positive attitude (Q14-24) and practice habits (Q25-27) regarding organ donation with dichotomous scale (Yes/No). RESULTS: As compared to males, females reported better mean+/-SD scores in knowledge (8.22+/-1.51) and practice (0.91+/-0.8); higher mean+/-SD attitude scores (8.55+/-1.56) were reported among males (p<0.001). While second year dental students had higher scores for their knowledge (8.55+/-1.56) and practice (1.02+/-0.44) compared to other year of training, third year students showed a significant higher mean attitude score (1.73+/-1.17) (p=0.02). Hindus and Muslims scored significantly lower mean knowledge, attitude and practice habits compared to others (Christians, Jains and Athesists) (p<0.001). There was a positive correlation between mean knowledge, attitude, and practice habits. CONCLUSION: There are an average level of knowledge and low levels of positive attitude and practice habits among studied dental students towards organ donation and transplantation. PMID- 26889370 TI - Knowledge Regarding Organ Donation and Willingness to Donate among Health Workers in South-West Nigeria. AB - BACKGROUND: Organ transplantation program in developing countries is still significantly dwarfed. Health workers are undeniably important in the success of transplantation. OBJECTIVE: To assess the knowledge and attitude of health workers toward organ donation in South-West Nigeria with a view to explaining reasons for these shortcomings. METHODS: In a cross-sectional study conducted on 850 health care workers, self-administered questionnaires were used to obtain information from participants. RESULTS: Of 850 participants, 766 (90.1%) returned their completed questionnaires. The mean+/-SD age of participants was 36.7+/-9.2 years. Majority (93.3%) of participants had heard of organ donation; 82.5% had desirable knowledge. Only 29.5% and 39.4% would be willing to donate and counsel potential organ donors, respectively; 36.5% would consider signing organ donation cards. Only 19.4% believed that organ transplantation is often effective and 63.4% believed they were permitted by their religion to donate. Permission by religion (OR 3.5; 95% CI 2.3 to 5.3), good knowledge (OR 2.9; 95% CI 1.4 to 5.7), readiness to sign donation cards (OR 2.6; 95% CI 1.7 to 3.8), discuss organ donation (OR 2.7; 95%CI 8.0 to 63.8), and knowing somebody who had donated (OR 2.9) independently influenced willingness to donate organ. CONCLUSION: There is disparity in knowledge of organ donation and willingness to donate among health care workers. Efforts should be intensified to give comprehensive and appropriate education to health care workers about organ donation to bridge this gap. PMID- 26889372 TI - Sofosbuvir and Simeprevir for the Treatment of Recurrent Hepatitis C with Fibrosing Cholestatic Hepatitis after Liver Transplantation. AB - Fibrosing cholestatic hepatitis (FCH) is an aggressive form of hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT), which frequently results in graft failure and death. Treatment of FCH remains challenging, and the optimal antiviral therapy is yet to be determined. Between November 2013 and early 2015, 62 patients with HCV cirrhosis underwent OLT at our transplant center, of whom, 5 patients developed recurrence HCV in the form of severe FCH and were treated with sofosbuvir and simeprevir (SOF-SMV) for 24 weeks. All patients achieved significant improvement of HCV viral load and had undetectable viral PCR at 6-8 week of treatment. The HCV RNA remained undetectable throughout treatment course. The first two patients achieved SVR at week 12 after completion of the treatment. There were significant histologic and biomarkers improvements after initiation of the treatment. One patient developed refractory pruritus and acute pancreatitis. The second, fourth and fifth patients had very benign treatment courses with no side effects recorded. The third patient was starting the treatment with multiple comorbid conditions. His course was complicated with hepatic artery thrombosis, and later developed sepsis and renal failure. Therefore, it seems that the combination of SOF-SMV is an efficacious oral regimen in OLT recipient with recurrent hepatitis C and FCH. However, safety profile needs to be carefully evaluated. PMID- 26889373 TI - NO2- Mediates the Heart Protection of Remote Ischemic Preconditioning. PMID- 26889374 TI - Post-renal Transplantation de novo Renal Cell Carcinoma in a Middle-aged Man. AB - Renal cell carcinoma is usually seen in the native kidney but may be seen in the renal allograft. We report a rare case of renal cell carcinoma in a 56-year-old renal allograft recipient who was transplanted for end-stage renal disease induced by analgesic nephropathy. This complication developed after 13 years of renal transplantation. Patient was investigated for hematuria and abdominal pain with a normal renal function. Computed tomography depicted a mass sized 9.0*7.3*6.8 cm that involved the upper pole of the transplant. There was no metastasis. The patient underwent radical allograft nephrectomy for the carcinoma that had extended up to the renal hilum. Histopathological examination revealed Furhman grade-1, clear cell variant, stage pT2 N0 M0. In the last visit, the patient was on maintenance hemodialysis via arterio-venous fistula and planned for cadaveric renal transplantation. Computed tomography could facilitate early diagnosis and proper management of patients with post-renal allograft renal cell carcinoma. PMID- 26889375 TI - Croup as Unusual Presentation of Post-transplantation Lymphoproliferative Disorder after Liver Transplantation in an 18-month-old Child. AB - Post-transplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation that occurs due to immunosuppression and other risk factors. PTLD may present with involvement of other organs and with unusual presentation. The presentation is often extranodal (e.g., in the gastrointestinal tract, lung, or the central nervous system). Herein, we report on a 1.5-year-old girl who underwent liver transplantation almost 5 months prior to admission. She was on medications such as tacrolimus and prednisolone. Her presentation was started with symptoms of the upper respiratory infection followed by croupy cough and respiratory distress with no response to usual treatments. She had respiratory arrest during broncoscopy. Therefore, emergency tracheostomy was done. Biopsy from the paratracheal mass revealed large B cell non-Hodgkin lymphoma (PTLD, monomorphic and high grade). This case presentation shows that persistent upper airway symptoms, particularly stridor and croupy cough, in children who underwent liver transplant should be further evaluated; the physician needs to have a high degree of clinical suspicion for the diagnosis of PTLD in this situation. PMID- 26889376 TI - Voluntary language switching in English-Spanish bilingual children. AB - Although bilingual children frequently switch between languages, the psycholinguistic mechanisms underlying the emerging ability to control language choice are unknown. We examined the mechanisms of voluntary language switching in English-Spanish bilingual children during a picture-naming task under two conditions: 1) single-language naming in English and in Spanish; 2) either language naming, when the children could use whichever language they wanted. The mechanism of inhibitory control was examined by analyzing local switching costs and global mixing costs. The mechanism of lexical accessibility was examined by analyzing the properties of the items children chose to name in their non dominant language. The children exhibited significant switching costs across both languages and asymmetrical mixing costs; they also switched into their non dominant language most frequently on highly accessible items. These findings suggest that both lexical accessibility and inhibition contribute to language choice during voluntary language switching in children. PMID- 26889377 TI - Universal minicircle sequence binding protein of Leishmania donovani regulates pathogenicity by controlling expression of cytochrome-b. AB - BACKGROUND: Leishmania contains a concatenated mitochondrial DNA, kDNA. Universal minicircle sequence binding protein (UMSBP), a mitochondrial protein, initiates kDNA replication by binding with a conserved universal minicircle sequence (UMS) of kDNA. Here, we describe first time in L. donovani the regulation of DNA binding activity of UMSBP and the role of UMSBP in virulence. METHODS: Insilco and EMSA study were performed to show UMS-binding activity of UMSBP. Tryparedoxin(TXN)-tryparedoxin peroxidase(TXNPx) assay as well as co overexpression of cytochrome-b5 reductase-like protein (CBRL) and tryparedoxin in L. donovani were done to know the regulation of DNA binding activity of UMSBP. Knockout and episomal-expression constructs of UMSBP were transfected in L. donovani. The cell viability assay and immunofluorescence study to know the status of kDNA were performed. Macrophages were infected with transfected parasites. mRNA level of cytochrome b, activity of complex-III, intracellular ATP level of both transfected promastigotes and amastigotes as well as ROS concentration and the level of apoptosis of transfected promastigotes were measured. Level of oxidative phosphorylation of both transfected and un transfected amastigotes were compared. Burden of transfected amastigotes in both macrophages and BALB/c mice were measured. RESULTS: L. donovani UMSBP is capable of binding with UMS, regulated by redox through mitochondrial enzymes, TXN, TXNPx and CBRL. Depletion of UMSBP (LdU(-/-)) caused kDNA loss, which decreased cytochrome-b expression [component of complex-III of electron transport chain (ETC)] and leads to the disruption of complex-III activity, decreased ATP generation, increased ROS level and promastigotes exhibited apoptosis like death. Interestingly, single knockout of UMSBP (LdU(-/+)) has no effect on promastigotes survival. However, single knockout in intracellular amastigotes demonstrate loss of mRNA level of cytochrome-b, disruption in the activity of complex-III and reduced production of ATP in amastigotes than wild type. This process interfere with the oxidative-phosphorylation and thereby completely inhibit the intracellular proliferation of LdU(-/+) amastigotes in human macrophages and in BALB/c mice. Amastigotes proliferation was restored as wild type after episomal expression of LdUMSBP in LdU(-/+) parasites (LdU(-/+)AB). CONCLUSION: The LdUMSBP regulates leishmanial mitochondrial respiration and pathogenesis. So, LdUMSBP may be an attractive target for rational drug designing and LdU(-/+) parasites could be considered as a live attenuated vaccine candidate against visceral leishmaniasis. PMID- 26889379 TI - Erratum to: Usability study of a simplified electroencephalograph as a health care system. AB - [This corrects the article DOI: 10.1186/s13755-015-0012-z.]. PMID- 26889378 TI - Morphological Evolution of Noble Metal Nanoparticles in Chloroform: Mechanism of Switching on/off by Protic Species. AB - The morphological stability/morphological reshaping of noble metal nanoparticles are studied experimentally in order to unravel the chemical mechanisms lying beneath. Gold and silver nanoparticles (AuNPs and AgNPs, respectively) formed in chloroformic environment are used, as model synthetic systems, to study phenomena of morphological change. The morphological evolution of NPs that follows their formation, is characterized by spectroscopy (UV-Visible, Raman and FTIR) and TEM (Transmission Electron Microscopy). The change of NP morphology involves the increase of the average NP size and the broadening of size distribution, in a close resemblance with the effect characteristically obtained from the Ostwald ripening. The effect of the poor solvating properties of chloroform in stabilizing small charged species (H+, Ag+, Au+) as well as the principle of electroneutrality of matter are analyzed in order to formulate a feasible reaction scheme consisting of a three-step processes: the generation of soluble intermediary species by corrosion of nanoparticles, the diffusion of intermediary species from one nanoparticle to another, and the re-deposition process involving the reduction of intermediary species. This basic reaction scheme is used as hypothesis to plan and perform experiments, which reveal that molecular oxygen dissolved in the dispersive medium can drive NP corrosion, however, protic species are also required as co-reactant. The polarity of the hydrogen bond and the ligand properties of the anions produced by deprotonation are feature of the protic species that enable/disable the corrosion and, in turn, the NP morphological evolution. PMID- 26889380 TI - Lactogenic hormones alter cellular and extracellular microRNA expression in bovine mammary epithelial cell culture. AB - BACKGROUND: Bovine milk contains not only a variety of nutritional ingredients but also microRNAs (miRNAs) that are thought to be secreted by the bovine mammary epithelial cells (BMECs). The objective of this study was to elucidate the production of milk-related miRNAs in BMECs under the influence of lactogenic hormones. RESULTS: According to a microarray result of milk exosomal miRNAs prior to cellular analyses, a total of 257 miRNAs were detected in a Holstein cow milk. Of these, 18 major miRNAs of interest in the milk were selected for an expression analysis in BMEC culture that was treated with or without dexamethasone, insulin, and prolactin (DIP) to induce a lactogenic differentiation. Quantitative polymerase chain reaction (qPCR) results showed that the expressions of miR-21-5p (P = 0.005), miR-26a (P = 0.016), and miR-320a (P = 0.011) were lower in the DIP treated cells than in the untreated cells. In contrast, the expression of miR 339a (P = 0.017) in the cell culture medium were lower in the DIP-treated culture than in the untreated culture. Intriguingly, the miR-148a expression in cell culture medium was elevated by DIP treatment of BMEC culture (P = 0.018). The medium-to-cell expression ratios of miR-103 (P = 0.025), miR-148a (P < 0.001), and miR-223 (P = 0.013) were elevated in the DIP-treated BMECs, suggesting that the lactogenic differentiation-induced secretion of these three miRNAs in BMECs. A bioinformatic analysis showed that the miRNAs down-regulated in the BMECs were associated with the suppression of genes related to transcriptional regulation, protein phosphorylation, and tube development. CONCLUSION: The results suggest that the miRNAs changed by lactogenic hormones are associated with milk protein synthesis, and mammary gland development and maturation. The elevated miR-148a level in DIP-treated BMECs may be associated with its increase in milk during the lactation period of cows. PMID- 26889381 TI - The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells. AB - BACKGROUND: Hypoxia and inflammation have been identified as hallmarks of cancer. A majority of hepatocellular carcinomas are preceded by hepatitis B- or C-related chronic infections suggesting that liver cancer development is promoted by an inflammatory microenvironment. The inflammatory cytokine oncostatin M (OSM) was shown to induce the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) under normoxic conditions in hepatocytes and hepatoma cells. HIF-1 alpha is known to orchestrate the expression of numerous genes, many of which code for metabolic enzymes that play key roles in the adaptation of cellular metabolism to low oxygen tension. RESULTS: Here, we show that OSM-induced upregulation of HIF-1 alpha reprograms cellular metabolism in three clones of the human hepatocyte cell line PH5CH (PH5CH1, PH5CH7, and PH5CH8) towards a hypoxia-like metabolic phenotype but has no significant effect on cellular metabolism of HepG2 and JHH-4 hepatoma cells. Although we observed only minor changes in glucose uptake and lactate secretion in PH5CH8 upon OSM treatment, we identified more pronounced changes in intracellular fluxes based on stable isotope labeling experiments. In particular, glucose oxidation in the tricarboxylic acid (TCA) cycle is reduced through pyruvate dehydrogenase kinase 1 (PDK1)-mediated inhibition of the pyruvate dehydrogenase complex, thereby reducing the oxidative TCA cycle flux. As a result of the impaired mitochondrial glucose and glutamine oxidation, the reductive isocitrate dehydrogenase flux was increased. CONCLUSIONS: We provide evidence that connects the inflammatory mediator OSM to a hypoxia-like metabolic phenotype. In the human hepatocyte cell line PH5CH, OSM-mediated upregulation of HIF-1 alpha and PDK1 can induce hypoxia-like metabolic changes, although to a lesser extent than hypoxia itself. Since PDK1 is overexpressed in several cancers, it might provide a causal link between chronic inflammation and malignant cellular transformation. PMID- 26889384 TI - Experiences of Iranian Nursing Faculty Members on Working in Conflict Climate. AB - BACKGROUND: Few studies have been conducted on role conflict in nursing faculty in the world. This research reports the first study about this subject in Iran. OBJECTIVES: The purpose of this research was to explore the experiences of role conflict in Iranian nursing faculty members. MATERIALS AND METHODS: We conducted a qualitative study using a conventional content analysis approach. We used semi structured and in-depth interviews by purposive sampling of 19 (15 instructors, three group managers and one educational assistant) participants to identify the influential factors of role conflict among nurse faculty members, working in seven nursing colleges in Iran. RESULTS: The three following categories emerged from data analysis: "roles Interference"; "role ambiguity", and "conflicting expectations". The main theme was "working in conflict climate". CONCLUSIONS: This study highlighted the influential factors that could produce role conflict for nursing faculty members. The results can help university leaders to improve nursing faculty working conditions. PMID- 26889382 TI - Objective and subjective sleep disorders in automated peritoneal dialysis. AB - BACKGROUND: Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unknown whether sleep and mood are disturbed while performing repeated overnight exchanges. OBJECTIVES: In this report, we aim to describe and compare the prevalence of sleep-disordered breathing (SDB), periodic limb movements (PLMS), poor sleep quality (SQ), and depression among APD patients compared with stages 3b-5 (estimated glomerular filtration rate <=44 ml/min/1.73 m2) chronic kidney disease (CKD) and hemodialysis (HD) patients. DESIGN: This is a cross-sectional, descriptive study. SETTING: Study participants were recruited from outpatient nephrology clinics, local dialysis centers, and the Thomas E. Starzl Transplant Institute in Western Pennsylvania between April 2004 and July 2009. PATIENTS: There were 186 participants in this study including 22 APD patients, 89 CKD patients, and 75 HD patients. MEASUREMENTS: In-home polysomnography was performed and two questionnaires were completed, the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire-9 (PHQ 9). METHODS: SDB and PLMS were quantified by in-home unattended polysomnography; poor SQ was defined by a score >5 on the PSQI, and the presence of moderate to severe depression was defined by a score >5 on the PHQ-9. RESULTS: The APD patients had a median age of 37.5 years, were predominantly female (72.7 %), and had a median body mass index (BMI) of 23.8 kg/m2. In univariate analyses, APD patients had significantly lower apnea-hypopnea index compared to HD patients by 12.2 points (likelihood ratio test p = 0.008) and revealed the least percent of TST with nocturnal hypoxemia compared to CKD patients by 2.7 points, respectively (likelihood ratio test p = 0.01). The APD group had also significantly greater stages 3 to 4 sleep compared to the CKD patients by 8.6 points (likelihood ratio test p = 0.009). In multivariate analyses and after adjustment for age, gender, race, and BMI, both APD and HD patients had higher average PSQI scores than CKD patients by 2.54 and 2.22 points, respectively (likelihood ratio test p = 0.005). No other comparisons of sleep parameters among groups reached statistical significance. LIMITATIONS: The limitations of this study are the small sample size of the APD population and the demographic and clinical differences among the three study groups. CONCLUSIONS: Despite differences in univariate analyses, after multivariate adjustment, APD patients had similar sleep parameters and sleep architecture and as poor SQ and symptoms of depression as HD patients. Future studies with larger APD cohorts are needed. PMID- 26889385 TI - Factors Associated With Serum Albumin in Diabetes Mellitus Type 2 With Microalbuminuria Using Non-Normal Mixed Models: A Prospective Cohort Study. AB - BACKGROUND: The globally increasing epidemic of diabetes will lead to serious problems including diabetic nephropathy and kidney diseases in near future. The first clinical diagnosable stage in a diabetic kidney disease is microalbuminuria (urinary albumin excretion of 30 - 300 g/24 hours). OBJECTIVES: This prospective cohort study investigated the risk factors of microalbuminuria in patients with type 2 diabetes who had been registered in endocrine and metabolism research center in Isfahan city, Iran. PATIENTS AND METHODS: This prospective cohort study was performed on 90 diabetic type 2 patients with microalbuminuria, who were selected according to the consecutive sample selection method during 6 years. Data were collected through regular and systematic measurements of serum albumin as the response variable and body mass index, systolic and diastolic blood pressure, the duration of diabetes, glycosylated hemoglobin (HbA1c), total cholesterol, triglyceride (TG), fasting blood sugar (FBS), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) as the related factors. Non normal mixed models were used to investigate the impact of effective factors on the amount of excreted serum albumin. RESULTS: According to the deviance information criterion (DIC = 56.2), the non-normal mixed effects model with the skewed t distribution had a best fit and indicated that HbA1c, HDL and total cholesterol had a significant effect on the amount of albumin in urine (P < 0.05). CONCLUSIONS: Using nonnormal mixed models may lead to the best results as compared to common normality assumption. PMID- 26889386 TI - Effects of Coriandrum sativum Syrup on Migraine: A Randomized, Triple-Blind, Placebo-Controlled Trial. AB - BACKGROUND: Migraine is one of the most common and debilitating neurological problems. Although numerous preventive drugs are used to treat migraine, their complications are unavoidable. Application of herbal medicine, especially well known medicinal plants, to treatment of chronic diseases, like migraine, could be effective. Coriandrum sativum L. (C. sativum) fruit is one of the most commonly prescribed herbs in Persian medicine, which has been used to treat headache. OBJECTIVES: This study was designed to evaluate the effects of C. sativum syrup on duration, severity and frequency of migraine. PATIENTS AND METHODS: A total of 68 migraineurs, who had the eligibility criteria, according to international headache society diagnostic criteria, were randomly assigned to intervention group (n = 34) or control group (n = 34). In addition to 500 mg of sodium valproate per day, in intervention group, they received 15 mL of Coriander fruit syrup and 15 mL of placebo syrup, in control group, three times a day, during a month. The subjects were followed for clinical efficacy at weeks 1, 2, 3 and 4. The number of migraine attacks per week, as well as the duration and severity of attacks, were evaluated. RESULTS: Of 68 patients randomized, 66 were included in analysis. The generalized estimating equations analysis showed that the Coriander fruit syrup decreased duration, severity and frequency of migraine, in the intervention group (P < 0.001). To be more precise, the mean migraine duration, severity and frequency, in the intervention group, were 5.7 hours, 3.65 units and about 50% less than control group, respectively. CONCLUSIONS: Results of this study showed that C. sativum fruit is efficient in reduction of the duration and frequency of migraine attacks and in diminishing pain degree. PMID- 26889387 TI - Frequency of Peripheral Arterial Disease in Patients With Chronic Venous Insufficiency. AB - BACKGROUND: It is estimated that about 15% (10% - 30% in most of the studies) of the total adult population has some aspects of the Chronic Venous Insufficiency (CVI). Frequency of the Peripheral Arterial Disease (PAD) in the adult population is 3% - 4%. Studies dealing with etiopathogenesis of leg ulcers show that between 10% and 18% of all ulcers are of mixed, arterial-venous origin. OBJECTIVES: The purpose of this study was to find out if there is a higher frequency of PAD among CVI patients in comparison with the control group, as well as to discover some common risk factors for CVI and PAD. PATIENTS AND METHODS: This cross-sectional descriptive study was conducted at the dermatovenereological clinic, clinical center of Vojvodina, Serbia. A total of 162 examinees were included. All patients were examined for the existence of CVI and staged according to CEAP (Clinical, etiology, anatomy and patophysiology) classification. In this way, 3 groups were formed: Patients with the mild forms of CVI (stage 1 - 4 by CEAP classification), 57 patients; patients with the severe forms of CVI (stage 5 and 6 by CEAP classification), 55 patients; control group (no CVI), 50 patients. Also, the Ankle Brachial Pressure Index (ABPI) was assessed in all subjects, and its value of <= 0.9 was set as criteria for diagnosis of PAD. The same sample was divided according to the presence of PAD into two groups. The most important risk factors for CVI and PAD were identified for each patient through complete examination, medical record and appropriate questionnaire. RESULTS: Our results showed that the risk factors for CVI were high Body Mass Index (BMI), hypertension, predominantly standing position during work and positive family history for CVI. In the same sample it was found that 28 (17.28%) patients had PAD. Relevant risk factors for PAD in the present study were: high BMI, hypertension, diabetes and a positive family history for PAD. Comparison of frequency of PAD among patients with severe forms of CVI and control group showed that this difference was statistically significant (P = 0.0275; OR 3.375; 95% CI 1.125 - 10.12). After multivariate analyses, adjusted odds ratio OR was still statistically significant. CONCLUSIONS: The peripheral arterial disease is more frequent in patients with the severe form of CVI, than in patients without CVI. Concomitant risk factors for CVI and PAD were high BMI and hypertension. In each patient with severe CVI it is necessary to determine the ABPI, in order to exclude the presence of PAD. PMID- 26889388 TI - Typical Absence Seizure Similarity to "Shokhous" in Iranian Traditional Medicine. PMID- 26889389 TI - Strategy for Mental Health Improvement of Iranian Stillborn Mothers From Their Perspective: A Qualitative Study. AB - BACKGROUND: Mothers got stressed when they are informed about the occurrence of stillbirth. Many researchers believe that the failure to provide the required care by health teams during this hard time is the main determinant of maternal mental health in the future. In other words, psychosocial support by medical care providers can significantly improve mental outcomes of mother after stillbirth. OBJECTIVES: This study aimed to explore stillborn mothers' suggested strategies to provide maternal mental health in the experience of stillbirth. PATIENTS AND METHODS: Twenty women who had experienced stillbirths participated in this qualitative content analysis study. They were selected through purposeful sampling method. Data were gathered by individual interviews recorded on audiotapes, transcripted and then analyzed. Then, transcriptions were coded and classified. Finally, 3 main categories and 9 subcategories were emerged. RESULTS: Analysis of participants' viewpoints and their opinions about strategies to provide maternal mental health in the experience of stillbirth lead to development of 3 main categories: "before delivery strategies" with 3 subcategories, "during labor strategies" with 3 subcategories, and "postpartum strategies" with 3 subcategories. Analyses of findings showed that, health care providers can mitigate some of the long-term negative mental outcomes of stillborn mothers by spending extra time with grieving mothers, facilitating bonding, and validating their emotional expressions. CONCLUSIONS: According to the results, revision and modification of the care plan in the experience of stillbirth seems necessary to improve mental health in these mothers. According to suggested strategies, midwives and health care providers are health professionals who can effectively and properly care for stillborn mothers. PMID- 26889390 TI - The Effectiveness of Assertiveness Training on the Levels of Stress, Anxiety, and Depression of High School Students. AB - BACKGROUND: Adolescence is a transition period from childhood to early adulthood. Because of the immense pressure imposed on adolescents due to the complications and ambiguities of this transition, their level of excitement increases and sometimes it appears in the form of sensitivity and intense excitement. OBJECTIVES: This study aimed at determining the effectiveness of assertiveness training on the levels of stress, anxiety, and depression of high school students. MATERIALS AND METHODS: This quasi-experimental study was conducted on high school students of Isfahan in academic year 2012 - 13. A total of 126 second grade high school students were collected according to simple random sampling method and divided into two groups: experimental with 63 participants and control with the same number. Data gathering instruments included a demographic questionnaire, Gambill-Richey assertiveness scale, and depression anxiety stress scales (DASS-21). Assertiveness training was carried out on the experimental group in 8 sessions; after 8 weeks, posttest was carried out on both groups. Statistical tests such as independent t test, repeated measures ANOVA, Chi-square test, and the Mann-Whitney test were used to interpret and analyze the data. RESULTS: The Chi-square and Mann-Whitney tests did not show significant statistical differences between the two groups in terms of demographic variables (P >= 0.05). Repeated measures ANOVA showed no significant difference between the mean scores for assertiveness before (100.23 +/- 7.37), immediately after (101.57 +/- 16.06), and 2 months after (100.77 +/- 12.50) the intervention in the control group. However, the same test found a significant difference between the mean score for assertiveness in the experimental group before (101.6 +/- 9.1), immediately after (96.47 +/- 10.84), and 2 months after (95.41 +/- 8.37) implementing the training program (P = 0.002). The independent t test showed no significant difference in the mean score for anxiety and stress between two groups before the assertiveness training program; however, 2 months after the intervention, the mean score for anxiety in the experimental group was found significantly lower than the control group. As for the mean score for depression, the independent t test showed no significant difference between two groups before training; however, despite the decrease in the mean scores for depression in the experimental group following the intervention, the difference was not significant (P = 0.09). CONCLUSIONS: The results of the current study show that conducting assertive training in high school students decreases their anxiety, stress, and depression. Given that high school years are among the most sensitive stages of one's life plus the fact that conducting such training programs besides their safe and low cost nature are effective and practical, it is highly recommended that such programs be carried out among high school adolescents. PMID- 26889391 TI - Is Routine Iron Supplementation Necessary in Pregnant Women With High Hemoglobin? AB - BACKGROUND: Iron supplementation is a chief component in prenatal care, with the aim of preventing anemia; however, extreme maternal iron status may adversely affect the birth outcome. Given the negative consequences of high maternal iron concentrations on pregnancy outcomes, it seems that iron supplementation in women with high hemoglobin (Hb) should be limited. OBJECTIVES: The aim of this study was to examine the effect of iron supplementation on iron status markers in pregnant women with high Hb. PATIENTS AND METHODS: In a randomized, double-blind, placebo-controlled trial, 86 pregnant women with Hb > 13.2 g/dL and ferritin > 15 MUg/l in the 16th - 20th week of pregnancy were randomized into experimental and control groups. From the 20th week until the end of pregnancy, the experimental group received one ferrous sulfate tablet containing 50 mg of elemental iron daily, while the control group received a placebo. Hb and ferritin levels at 37 - 39 weeks of pregnancy were evaluated and compared. In addition, after delivery the birth weight was measured in two groups and compared. RESULTS: There were statistically significant differences between the two groups in Hb (p = 0/03) and ferritin (p = 0/04) levels at the end of pregnancy, but the incidence of anemia exhibited no difference in either group (p < 0/001). In addition, the mean of birth weight in experimental group and control group were 3391/56 +/- 422, 3314/06 +/- 341, respectively and it was not significant difference (p = 0.2). CONCLUSIONS: Not using iron supplementation did not cause of anemia in women with Hb concentrations greater than 13.2 g/dL during pregnancy; thus, the systematic care and control of iron status markers without iron supplementation is recommended for these women. PMID- 26889392 TI - Expression and Clinical Significance of Tumor Necrosis Factor Receptor-Associated Factor 6 in Patients With Colon Cancer. AB - BACKGROUND: Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been reported to be highly expressed in many tumor tissues, but it is still of value to detect its expression in patients with colon cancer and to clarify its clinical significance. OBJECTIVES: To study the expression and clinical significance of TRAF6 in patients with colon cancer. PATIENTS AND METHODS: A total of 135 patients with colon cancer who underwent surgery at our hospital from February 2008 to March 2013 were selected. The expression levels of TRAF6 protein in tumor and paracancerous tissues were detected with the immunohistochemical method to evaluate their clinical significance. RESULTS: The positive expression rate of TRAF6 in tumor tissues was 66.7%, which was significantly higher than in normal paracancerous tissues (18.5%). The positive expression rate of TRAF6 was significantly correlated with Dukes' staging, degree of differentiation, and lymphatic metastasis (P < 0.05), but not gender or age (P > 0.05). The expression level of TRAF6 was negatively correlated with the 5-year survival rate; patients with high TRAF6 expression levels had significantly decreased survival compared to those with low levels (P < 0.05). CONCLUSIONS: TRAF6 plays an important role in the onset of colon cancer; therefore, drugs targeting it may have great clinical significance in the treatment of this disease. PMID- 26889393 TI - An Unusual Complication of Ventriculoperitoneal Shunt: Urinary Bladder Stone Case Report and Literature Review. AB - INTRODUCTION: Ventriculoperitoneal (V-P) shunt surgery is the most common technique used for the treatment of hydrocephalus. The migration of ventriculoperitoneal shunt to the bladder is rare. Only two cases have been previously reported in the literature. CASE PRESENTATION: We report on a 38-year old male who had hydrocephalus and V-P shunt for 12 years. Two years ago, he found himself with recurrent urinary tract infections, haematuria and urges incontinence, and then he was diagnosed with bladder perforation and merge stones. The patient had an abdominal operation to cut off and take out the shunt catheter, as well as a transurethral holmium laser lithotripsy. CONCLUSIONS: Bladder perforation and stones are rare examples of complications in V-P surgical procedures. Controlling the effective length of the terminal V-P shunt and modifying it appropriately can effectively reduce these complications. PMID- 26889394 TI - Effects of a New Metabolic Conditioning Supplement on Perioperative Metabolic Stress and Clinical Outcomes: A Randomized, Placebo-Controlled Trial. AB - BACKGROUND: Insulin resistance is a measure of metabolic stress in the perioperative period. Before now, no clinical trial has determined the summative effects of glutamine, L-carnitine, and antioxidants as metabolic conditioning supplements in the perioperative period. OBJECTIVES: The purpose of this study was to determine the effects of a new conditioning supplement on perioperative metabolic stress and clinical outcomes in non-diabetic patients. PATIENTS AND METHODS: In this randomized controlled trial, 89 non-diabetic patients scheduled for coronary artery bypass grafting, with ejection fractions above 30%, were selected. Using the balanced block randomization method, the patients were allocated to one of four study arms: 1) SP (supplement/placebo): supplement seven days before and placebo 30 days after the surgery; 2) PS: placebo before and supplement after the surgery; 3) SS: supplement before and after the surgery; and 4) PP: placebo before and after the surgery. The supplement was composed of glutamine, L-carnitine, vitamin C, vitamin E, and selenium, which was manufactured for the first time by this research team. Five blood samples were drawn: seven days preoperatively, at the entrance to the operating room, while leaving the operating room, seven days postoperatively, and 30 days postoperatively. Levels of glucose, insulin, and HbA1c were measured in blood samples. Insulin resistance and sensitivity were calculated using a formula. Surgical complications were assessed 30 days postoperatively. Data analysis was done using one-way ANOVA, the Chi-square test, and a general linear model repeated-measures analysis with Bonferroni adjustment. RESULTS: Blood glucose levels were increased postoperatively in the four groups (< 0.001), but a significantly higher increase occurred in the PP group compared to the SP (0.027), PS (0.026), and SS (0.004) groups. The superficial wound infection rate was significantly different between the four groups (0.021): 26.08% in PP, 9.09% in SP, 4.54% in PS, and 0% in SS. CONCLUSIONS: Our new metabolic conditioning supplement, whether given pre- or postoperatively, led to better perioperative glycemic control and decreased postsurgical wound infections in non-diabetic patients. PMID- 26889395 TI - High Frequency of Class 1 Integrons in Escherichia coli Isolated From Patients With Urinary Tract Infections in Yasuj, Iran. AB - BACKGROUND: Most urinary tract infections (UTI) are caused by Escherichia coli. Integrons have an important role in distributing antibiotic resistance genes among bacteria. OBJECTIVES: The aim of this study was to investigate the presence of class 1, 2 and 3 integrons and their association with antibiotic resistance in E. coli isolated from patient with UTI in Yasuj, Iran. PATIENTS AND METHODS: In this cross-sectional study a total of 200 E. coli were collected from 1820 patients diagnosed with UTI that had been referred to two clinical laboratories between February 2013 and November 2014 in Yasuj city, southwest of Iran. Susceptibility of isolates to 11 different antibiotics was determined by the disk agar diffusion method. multiplex-polymerase chain reaction (PCR) was used for detection of class 1, 2 and 3 integrons. The data were analyzed using the SPSS software (version 16) and the chi-square test. A P value of < 0.05 was considered statistically significant. RESULTS: The highest rate of resistance was observed toward cephalothin (99%) and amoxicillin (76%) while only two (1%) isolates showed resistance to imipenem. Overall, 79% of isolates were multi drug resistant (MDR). Class 1 and 2 integrons were detected in 104 (52%) and 5 (2.5%) isolates respectively, while none of the isolates were positive for class 3 integrons. A significant association was observed between the presence of integrons and resistance to co-trimoxazole, nalidixic acid, ciprofloxacin, amoxicillin, ceftazidime and tetracycline (P < 0.05). CONCLUSIONS: High MDR isolates of E. coli were observed in this study. The significant association between class 1 integrons and resistance to ciprofloxacin, nalidixic acid, co-trimoxazole, amoxicillin, ceftazidime and tetracycline showed that class 1 integrons have an important role in resistance to these antibiotics in this region. PMID- 26889397 TI - Leisure Activity Patterns and Marital Conflict in Iran. AB - BACKGROUND: Over the past few decades, the association between leisure activity patterns and marital conflict or satisfaction has been studied extensively. However, most studies to date have been limited to middle-class families of developed societies, and an investigation of the issue, from a developing country perspective like Iran, is non-existent. OBJECTIVES: In an observational, analytical, cross-sectional study we aimed to investigate the relationship between leisure activity patterns and marital conflict in a nationally representative sample of Iranian married males. PATIENTS AND METHODS: Using the cluster sampling method, a representative sample of 400 Iranian married individuals from seven provinces of Iran was surveyed. Self-administered surveys included a checklist collecting demographic and socioeconomic characteristics of the enrolled participants, leisure time questionnaire, and marital conflict questionnaire. The main patterns of leisure activity were derived from principal component analysis. For each pattern, factor scores were calculated. The relationship between factor scores and marital conflict were assessed using multivariate linear regression models accounting for the potential confounding effects of age, education, socioeconomic status, job status, number of children, duration of marriage, and time spent for leisure. RESULTS: Two hundred and ninety nine respondents completed the leisure time and marital conflict questionnaires. Five major leisure patterns were identified accounting for 60.3% of the variance in data. The most dominant pattern was family-oriented activities (e.g. spending time with family outdoors and spending time with family indoors) and was negatively linked to marital conflict (standardized beta= -0.154, P = 0.013). Of the four remaining patterns, three only included individual activities and one was a family-individual composite. Individual patterns exhibited discrepant behavior; while the pattern involving activities like 'watching TV', 'non purposive time spending', and 'napping' was positively associated with conflict (standardized beta = 0.165, P = 0.009) and the other two were not. The mixed family-individual pattern was also positively associated with marital conflict (standardized beta = 0.240, P < 0.001). CONCLUSIONS: Among Iranian married men, family-based leisure activities are linked to a lower level of marital conflict. The associations for individual patterns are less congruent. PMID- 26889396 TI - Adolescents' Experiences When Living With a Parent With Cancer: A Qualitative Study. AB - BACKGROUND: Cancer affects not only the patient but also their entire family, especially adolescents. Adolescents whose parents are ill may manifest their distress through changes in school performance, physical complaints of pain and discomfort, as well as changes in social and interpersonal relations. There has been very little research about the effects of cancer on adolescents in Iran. OBJECTIVES: The purpose of this qualitative study was to explore the Iranian adolescents' experiences when living with a parent with cancer. PATIENTS AND METHODS: In this research, the descriptive-explorative approach was used. There were a total of 27 participants. Purposeful sampling was used and data collection methods were semi-structured deep interviews. Constant comparative analysis was used to study the data. RESULTS: The findings of this study showed that the main experiences of these adolescents were categorized into seven themes: 1- psychological problems of adolescents; 2- supportive-educative needs; 3- cancer as a two edged sword in family relationships; 4- stages of confrontation with the parent's cancer; 5- effect of cancer on social dimensions; 6- affective and helpful supportive agents; 7- Need of support for education under special conditions. CONCLUSIONS: This research showed that Iranian adolescents had the same experiences as other adolescents in other countries in many aspects yet in some issues, such as religious strategy, they had strong religious beliefs that would help them cope with their parents' cancer. Also it was shown that we must plan a program in which education and support should be provided to enable adolescents to cope with this detrimental situation with minimal disruption. PMID- 26889398 TI - Rectal Diclofenac Versus Rectal Paracetamol: Comparison of Antipyretic Effectiveness in Children. AB - BACKGROUND: Fever is the most common complaint in pediatric medicine and its treatment is recommended in some situations. Paracetamol is the most common antipyretic drug, which has serious side effects such as toxicity along with its positive effects. Diclofenac is one of the strongest non-steroidal anti inflammatory (NSAID) drugs, which has received little attention as an antipyretic drug. OBJECTIVES: This study was designed to compare the antipyretic effectiveness of the rectal form of Paracetamol and Diclofenac. PATIENTS AND METHODS: This double-blind controlled clinical trial was conducted on 80 children aged six months to six years old. One group was treated with rectal Paracetamol suppositories at 15 mg/kg dose and the other group received Diclofenac at 1 mg/kg by rectal administration (n = 40). Rectal temperature was measured before and one hour after the intervention. Temperature changes in the two groups were compared. RESULTS: The average rectal temperature in the Paracetamol group was 39.6 +/- 1.13 degrees C, and 39.82 +/- 1.07 degrees C in the Diclofenac group (P = 0.37). The average rectal temperature, one hour after the intervention, in the Paracetamol and the Diclofenac group was 38.39 +/- 0.89 degrees C and 38.95 +/- 1.09 degrees C, respectively (P = 0.02). Average temperature changes were 0.65 +/ 0.17 degrees C in the Paracetamol group and 1.73 +/- 0.69 degrees C in the Diclofenac group (P < 0.001). CONCLUSIONS: In the first one hour, Diclofenac suppository is able to control the fever more efficient than Paracetamol suppositories. PMID- 26889399 TI - Evaluation of Iron Oxide Nanoparticles Toxicity on Liver Cells of BALB/c Rats. AB - BACKGROUND: Because of their unique magnetic properties, Fe3O4 nanoparticles (Fe3O4-NPs) have extensive applications in various biomedical aspects. Investigation of the possible adverse aspects of these particles has lagged far behind their fast growing application. OBJECTIVES: The current study aimed to evaluate the toxicity of Fe3O4-NPs in the liver of mice. MATERIALS AND METHODS: In the present clinical trial, 90 BALB/c mice were randomly divided in 15 groups. Five control groups were fed by usual water and food. Five placebo groups were gavaged with physiological serum in doses of 25, 50, 75, 150, and 300 micrograms per gram of body weight (MUg/gr). Five experimental groups were gavaged with Fe3O4-NPs, in doses of 25, 50, 75, 150, and 300 MUg/gr. This pattern was repeated every other day, for 3 days. Then, the levels of liver enzymes [alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)] were compared between these groups. The histological alterations of livers were examined, as well. For statistical analysis, Kruskal-Wallis and Mann Whitney, with type I Bonferroni correction, as post-hoc, have been used. RESULTS: The administration of 150 and 300 MUg/gr doses of Fe3O4-NPs were associated with significant elevation in liver enzymes, compared to controls (P < 0.0001). Furthermore, the histopathological effects were observed in the liver tissue of these groups. However, in groups treated with lower doses of Fe3O4-NPs, no significant adverse effect was observed. CONCLUSIONS: Based on our results, the administration of Fe3O4-NPs causes dose dependent adverse effects on liver. PMID- 26889400 TI - Central Nervous System Depressants Poisoning and Ventilator Associated Pneumonia: An Underrated Risk Factor at the Toxicological Intensive Care Unit. AB - BACKGROUND: Ventilator-Associated Pneumonia (VAP) is the main cause of nosocomial infection at intensive care units (ICUs), which causes high mortality and morbidity. OBJECTIVES: The objective of the present survey was to identify the VAP risk and prognostic factors among poisoned patients, who were admitted to the toxicological ICU (TICU), especially central nervous system (CNS) depressants due to their prevalence and importance. PATIENTS AND METHODS: A case-control study was conducted at the Loghman Hakim hospital between March 2013 and March 2014. Among 300 poisoned patients with mechanical ventilator >= 48 hours, 150 patients, who had developed microbiologically-confirmed VAP were considered as the VAP group and 150 without VAP were defined as the control group. The following data were collected; age, gender, type of poisoning, glasgow coma score, Acute physiology and chronic health evaluation (APACHE) II score, length of hospital stay, previous antibiotic use, microbial culture of the trachea, body temperature, leukocyte count, and patients' outcome. Based on the type of poisoning, patients were divided into three groups including: opioid, CNS depressants and others. All data were expressed as means (SD) for continuous variables and frequencies for categorical variables. Logistic regression was used to determine the relationship between risk factors and VAP. RESULTS: The mean age of the patients was 33.9 +/- 14.3 years. The probable VAP incidence and mortality were 22% and 18.6%, respectively. The rate of CNS depressant versus opioid use (odds ratio, 3.74; P < 0.027), APACHE II (odds ratio, 1.28; P < 0.000) and length of hospital stay (odds ratio, 2.15; P < 0.000) were the independent risk factors for VAP. While, the APACHE II score (odds ratio, 1.12; P < 0.044) and length of hospital stay (odds ratio, 2.15; P < 0.000) were the independent predictors of VAP mortality among these patients. The most common microorganisms in VAP cases were Methicillin-Resistant Staphylococcus aureus (MRSA) and Acinetobacter sp. (56.7% and 12.7%, respectively). CONCLUSIONS: Central nervous system depressant was an important risk factor for VAP among poisoned patients. Hypoventilation due to CNS depression can lead to VAP. The APACHE II and length of hospital stay were shown as independent predictors of VAP and mortality among these patients. PMID- 26889402 TI - Adolescent Substance Use and Comorbid Psychopathology: Emotion Regulation Deficits as a Transdiagnostic Risk Factor. AB - Rates of substance use and comorbid psychopathology peak during adolescence, highlighting the need to identify transdiagnostic risk processes that cut across conditions and elucidate early embedded risk factors for comorbidity across development. The current review highlights emotion regulation deficits as a core transdiagnostic risk factor underlying the development of substance use, addiction, and comorbid psychopathology in adolescence. We present the dual systems model of neurological development to highlight adolescence as a critical period of increased risk for emotion regulation difficulties, corresponding risk behaviors, and psychopathology. We describe malfunction in the neurobiological regulation system underlying the relationship between emotion regulation and risk for addiction and comorbidity. We pull from two established developmental theories including both the externalizing pathway and the internalizing pathway to substance use disorders, which together highlight how early embedded risk in the form of emotion regulation deficits can explain mechanisms underlying the development of addiction and comorbid psychiatric disorders. PMID- 26889401 TI - Bivariate Trajectories of Substance Use and Antisocial Behavior: Associations with Emerging Adult Outcomes in a High-Risk Sample. AB - Substance use and antisocial behavior are complex, interrelated behaviors. The current study identified model trajectory classes defined by concurrent substance use and antisocial behavior and examined trajectory associations with emerging adult outcomes. Participants from a high-risk sample of youth (n=536; 73% male) completed interviews at baseline (mean age= 16.1 years) and followup (mean age= 22.6 years). Latent class growth analyses identified five trajectory classes based on alcohol/drug use (AOD) and antisocial behavior (ASB): Dual Chronic, Increasing AOD/Persistent ASB, Persistent AOD/Adolescent ASB, Decreasing Drugs/Persistent ASB, and Resolved. Many individuals (56%) exhibited elevated/increasing AOD, and most (91%) reported ASB decreases. Those associated with the Dual Chronic class had the highest rates of substance dependence, antisocial personality disorder (ASPD), and negative psychosocial outcomes. There were no differences in adult role attainment across classes. Conjoint examination of these behaviors provides greater detail regarding clinical course and can inform secondary prevention and intervention efforts. PMID- 26889403 TI - Vitamin C and functional iron deficiency anemia in hemodialysis. PMID- 26889404 TI - Smads as therapeutic targets for chronic kidney disease. AB - Renal fibrosis is a hallmark of chronic kidney disease (CKD). It is generally thought that transforming growth factor-beta1 (TGF-beta1) is a key mediator of fibrosis and mediates renal scarring positively by Smad2 and Smad3, but negatively by Smad7. Our recent studies found that in CKD, TGF-beta1 is not a sole molecule to activate Smads. Many mediators such as angiotensin II and advanced glycation end products can also activate Smads via both TGF-beta dependent and independent mechanisms. In addition, Smads can interact with other signaling pathways, such as the mitogen-activated protein kinase and nuclear factor-kappaB (NF-kappaB) pathways, to regulate renal inflammation and fibrosis. In CKD, Smad2 and Smad3 are highly activated, while Smad7 is reduced or lost. In the context of fibrosis, Smad3 is pathogenic and mediates renal fibrosis by upregulating miR-21 and miR-192, but down-regulating miR-29 and miR-200 families. By contrast, Smad2 and Smad7 are protective. Overexpression of Smad7 inhibits both Smad3-mediated renal fibrosis and NF-kappaB-driven renal inflammation. Interestingly, Smad4 has diverse roles in renal fibrosis and inflammation. The complexity and distinct roles of individual Smads in CKD suggest that treatment of CKD should aim to correct the imbalance of Smad signaling or target the Smad3 dependent genes related to fibrosis, rather than to block the general effect of TGF-beta1. Thus, treatment of CKD by overexpression of Smad7 or targeting Smad3 dependent miRNAs such as downregulation of miR-21 or overexpression of miR-29 may represent novel therapeutic strategies for CKD. PMID- 26889407 TI - Association between vascular access failure and microparticles in hemodialysis patients. AB - BACKGROUND: Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses. METHODS: We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42- or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration. RESULTS: The levels of EMP (both CD31+CD42- and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42-EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42-EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival >= 4 years). CONCLUSION: Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients. PMID- 26889408 TI - The effect of intravenous ascorbic acid in hemodialysis patients with normoferritinemic anemia. AB - BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency often develop resistance to recombinant human erythropoietin (rhEPO). Recent studies have shown that intravenous ascorbic acid (IVAA) administration could override rhEPO resistance in HD patients. This study was undertaken to test the effects of IVAA in HD patients with normoferritinemic functional iron deficiency accompanied by EPO-hyporesponsive anemia. METHODS: Fifty-eight HD patients with normoferritinemic anemia (between 100 and 500 MUg/L) were included and divided into the control (N=25) and IVAA (N=33) groups. IVAA patients received 500 mg of IVAA with each dialysis session for 3 months and an additional 4-month follow-up after the end of the therapy. RESULTS: Twenty patients had a response to IVAA with a significant increase in hemoglobin level (Hgb>1.0 g/dL) and reduction of weekly rhEPO dosage compared with the control group after 3 months of treatment (P<0.05). Compared with non-responders, transferrin saturation (TSAT) was significantly decreased in the responders group (26+/-11 vs. 35+/-14%, P<0.05) on baseline data. There was a significant increase in serum iron and TSAT (baseline vs. 3 months, serum iron 57+/-22 vs. 108+/-22 MUg/dL, TSAT 26+/-11 vs. 52+/-7%, P<0.05) and a decrease in serum ferritin (377+/-146 vs. 233+/-145 ng/mL, P<0.05) in the responders group (N=20), but no significant changes in the control and non responders groups (N=13) at 3-month treatment. CONCLUSION: IVAA can be a potent and effective adjuvant therapy for HD patients with rhEPO-resistant normoferritinemic anemia. In addition, IVAA can reduce the dosage of rhEPO for anemia correction. PMID- 26889409 TI - The effect of depression and health-related quality of life on the outcome of hemodialysis patients. AB - BACKGROUND: In hemodialysis (HD) patients, traditional risk factors cannot explain all of the mortality and morbidity. This study was designed to investigate the effect of depression and health-related quality of life (HRQOL) on prognosis in maintenance HD patients. METHODS: In February 2008, the Beck's Depression Inventory and the Kidney Dialysis Quality of Life-Short Form were utilized to measure depression and HRQOL. Until February 2011, the mortality, cardiovascular events, infection, and hospitalization were investigated, retrospectively. RESULTS: Among the 166 patients, the 3-year cumulative survival rate was 88.8%, and the depression did not affect survival (depression vs. nondepression: 91.8% vs. 87.2%, P=0.437). The upper tertiles in physical component summary (PCS) were correlated with lower mortality (OR, 0.12; P=0.05) and fewer cardiovascular events (OR, 0.09; P=0.024) than the lower tertiles. The upper tertiles in kidney disease component summary (KDCS) were associated with less hospitalization than the lower tertiles (OR, 0.38; P=0.024). After adjusting for multiple variables including age, comorbidity index, and albumin, upper tertiles in PCS were correlated with fewer cardiovascular events than the lower tertiles (OR, 0.08; P=0.038). CONCLUSION: The cross-sectional survey of whether HD patients had depression was not significantly associated with mortality and morbidity. HRQOL was correlated with mortality, cardiovascular events and hospitalization. PMID- 26889405 TI - Cardiorenal syndrome and vitamin D receptor activation in chronic kidney disease. AB - Cardiorenal syndrome (CRS) refers to a constellation of conditions whereby heart and kidney diseases are pathophysiologically connected. For clinical purposes, it would be more appropriate to emphasize the pathophysiological pathways to classify CRS into: (1) hemodynamic, (2) atherosclerotic, (3) uremic, (4) neurohumoral, (5) anemic-hematologic, (6) inflammatory-oxidative, (7) vitamin D receptor (VDR) and/or FGF23-, and (8) multifactorial CRS. In recent years, there have been a preponderance data indicating that vitamin D and VDR play an important role in the combination of renal and cardiac diseases. This review focuses on some important findings about VDR activation and its role in CRS, which exists frequently in chronic kidney disease patients and is a main cause of morbidity and mortality. Pathophysiological pathways related to suboptimal or defective VDR activation may play a role in causing or aggravating CRS. VDR activation using newer agents including vitamin D mimetics (such as paricalcitol and maxacalcitol) are promising agents, which may be related to their selectivity in activating VDR by means of attracting different post-D-complex cofactors. Some, but not all, studies have confirmed the survival advantages of D-mimetics as compared to non-selective VDR activators. Higher doses of D-mimetic per unit of parathyroid hormone (paricalcitol to parathyroid hormone ratio) is associated with greater survival, and the survival advantages of African American dialysis patients could be explained by higher doses of paricalcitol (>10 MUg/week). More studies are needed to verify these data and to explore additional avenues for CRS management via modulating VDR pathway. PMID- 26889411 TI - Inherited protein S deficiency due to a novel nonsense mutation in the PROS1 gene in the patient with recurrent vascular access thrombosis: A case report. AB - Vascular access thrombosis is one of the major causes of morbidity in patients maintained on chronic hemodialysis. Thrombophilia has been recognized as a risk factor of vascular access thrombosis. The authors report a case of inherited protein S deficiency associated with vascular access thrombotic events. DNA sequence analysis of the PROS1 gene identified a novel heterozygous nonsense mutation in exon 10 by transition of AAG (lysine) to TAG (stop codon) at codon 473 (c.1417A>T, p.K473X). Results from the study suggest that the inherited protein S deficiency due to a PROS1 gene mutation may cause vascular access thrombosis in hemodialysis patients. PMID- 26889410 TI - Brief Report: Renal replacement therapy in Korea, 2010. AB - The Korean Society of Nephrology (KSN) launched the official End-Stage Renal Disease (ESRD) Patient Registry in 1985 and the Internet online registry program was opened in 2001. The ESRD Registry Committee of KSN has collected data on dialysis therapy in Korea through the online registry program in the KSN Internet website. The increasing number of elderly people and diabetic patients in Korea has resulted in a very rapid increase in the number of ESRD patients. The total number of ESRD patients was 58,860 (hemodialysis [HD], 39,509; peritoneal dialysis [PD], 7309; and functioning kidney transplant [KT], 12,042). The prevalence of ESRD was 1144.4 patients per million population (PMP), and the proportion of renal replacement therapy was HD, 67.1%; PD, 12.4%; and KT, 20.5%. The number of new ESRD patients in 2010 was 9335 (HD, 7204; PD, 867; and KT, 1264; the incidence rate was 181.5 PMP). The primary causes of ESRD were diabetic nephropathy (45.2%), hypertensive nephrosclerosis (19.2%), and chronic glomerulonephritis (11.3%). The mean urea reduction ratio was 67.9% in male HD patients and 73.9% in female HD patients. The mean Kt/V was 1.394 in male patients and 1.659 in female patients. Five-year survival rates of male and female dialysis patients were 64.9% and 67.3%, respectively. PMID- 26889413 TI - Radiocontrast-induced nephropathy in patients with liver cirrhosis and chronic kidney disease. PMID- 26889406 TI - The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities. AB - The growth hormone-insulin-like growth factor-insulin-like growth factor binding protein (GH-IGF-IGFBP) axis plays a critical role in the maintenance of normal renal function and the pathogenesis and progression of chronic kidney disease (CKD). Serum IGF-I and IGFBPs are altered with different stages of CKD, the speed of onset, the amount of proteinuria, and the potential of remission. Recent studies demonstrate that growth failure in children with CKD is due to a relative GH insensitivity and functional IGF deficiency. The functional IGF deficiency in CKD results from either IGF resistance due to increased circulating levels of IGFBPs or IGF deficiency due to increased urinary excretion of serum IGF-IGFBP complexes. In addition, not only GH and IGFs in circulation, but locally produced IGFs, the high-affinity IGFBPs, and low-affinity insulin-like growth factor binding protein-related proteins (IGFBP-rPs) may also affect the kidney. With respect to diabetic kidney disease, there is growing evidence suggesting that GH, IGF-I, and IGFBPs are involved in the pathogenesis of diabetic nephropathy (DN). Thus, prevention of GH action by blockade either at the receptor level or along its signal transduction pathway offers the potential for effective therapeutic opportunities. Similarly, interrupting IGF-I and IGFBP actions also may offer a way to inhibit the development or progression of DN. Furthermore, it is well accepted that the systemic inflammatory response is a key player for progression of CKD, and how to prevent and treat this response is currently of great interest. Recent studies demonstrate existence of IGF-independent actions of high affinity and low-affinity-IGFBPs, in particular, antiinflammatory action of IGFBP 3 and profibrotic action of IGFBP-rP2/CTGF. These findings reinforce the concept in support of the clinical significance of the IGF-independent action of IGFBPs in the assessment of pathophysiology of kidney disease and its therapeutic potential for CKD. Further understanding of GH-IGF-IGFBP etiopathophysiology in CKD may lead to the development of therapeutic strategies for this devastating disease. It would hold promise to use of GH, somatostatin analogs, IGFs, IGF agonists, GHR and insulin-like growth factor-I receptor (IGF-IR) antagonists, IGFBP displacer, and IGFBP antagonists as well as a combination treatment as therapeutic agents for CKD. PMID- 26889412 TI - A case of Creutzfeldt-Jakob disease in a patient on hemodialysis. AB - We report an unusual case of probable Creutzfeldt-Jakob disease (CJD) in hemodialysis patient. A woman 59 years of age with a past history of hypertension and end-stage renal disease presented with a stuporous state preceded by rapidly progressive cognitive dysfunction, myoclonus, and akinetic mutism. At first, the cause of the altered mental status was assumed to be uremic or hypertensive encephalopathy combined with fever. Proper managements, however, did not improve the neurologic symptoms. Diffusion-weighted magnetic resonance imaging revealed bilaterally asymmetric high signal intensity in both basal ganglia and cerebral cortices. Electroencephalography showed diffuse generalized theta-to-delta range slow wave and intermittent medium-to-high voltage complexes with a characteristic triphasic pattern on both hemispheres. Cerebrospinal fluid assay for the 14-3-3 protein was positive and diagnostic of CJD. PMID- 26889414 TI - Current concepts of the podocyte in nephrotic syndrome. AB - Nephrotic syndrome is a disorder of the glomerular filtration barrier, and central to the filtration mechanism of the glomerular filtration barrier is the podocyte. We are starting to better understand how this cell, with its unique architectural features, fulfils its exact filtration properties. The multiprotein complex between adjacent podocyte foot processes, the slit diaphragm, is essential to the control of the actin cytoskeleton and cell morphology. Many of the proteins within the slit diaphragm, including nephrin, podocin, transient receptor potential-6 channel, and alpha-actinin-4, have been identified via genetic studies of inherited nephrotic syndromes. Signaling from slit diaphragm proteins to the actin cytoskeleton is mediated via the Rho GTPases. These are thought to be involved in the control of podocyte motility, which has been postulated as a focus of proteinuric pathways. Nephrotic syndrome is currently treated with immunosuppressive therapy, with significant adverse effects. These therapies may work in nephrotic syndrome due to specific effects on the podocytes. This review aims to describe our current understanding of the cellular pathways and molecules within the podocyte relevant to nephrotic syndrome and its treatment. With our current knowledge of the cellular biology of the podocyte, there is much hope for targeted therapies for nephrotic syndromes. PMID- 26889417 TI - Complete remission induced by tacrolimus and low-dose prednisolone in adult minimal change nephrotic syndrome: A pilot study. AB - BACKGROUND: Few clinical trials have examined the replacement of steroids with other immunosuppressive drugs as a primary treatment modality for minimal change disease (MCD) in adults. We studied the efficacy of tacrolimus to induce complete remission (CR) in adults with MCD. METHODS: We enrolled 14 adults with MCD and nephrotic-range proteinuria. All patients were treated with oral tacrolimus 0.05 mg/kg twice daily and prednisolone 0.5 mg/kg/day. CR was defined as a urine protein to creatinine ratio of<0.2 g protein/g creatinine (g/g cr). The primary outcome was cumulative percentage of CR during 16 weeks. RESULTS: The mean urine protein to creatinine ratio at enrollment was 10.9 g/g cr (range: 4.2-18.1 g/g cr). The trough tacrolimus level was maintained at 5.99+/-2.63 ng/mL. CR was achieved by 13/14 (92.8%) patients within 8 weeks. The cumulative CR rate was 7.7% (1/14), 64.2% (9/14), 71.3% (10/14), and 92.9% (13/14) at 1 week, 2 weeks, 4 weeks, and 8 weeks, respectively. The one remaining patient achieved CR at 20 weeks after treatment, who was followed up for a further 4 weeks. The mean time to achieve CR in the 14 patients was 4.64+/-5.11 (1-20) weeks. Three cases suffered adverse events of abdominal pain, diarrhea, or new-onset diabetes mellitus. CONCLUSION: Tacrolimus and low-dose prednisolone therapy induced CR rapidly (71.3% by 4 weeks and 100% by 20 weeks) and effectively in adult patients with MCD. PMID- 26889418 TI - Hemorrhagic fever with renal syndrome and coexisting hantavirus pulmonary syndrome. AB - Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS). HPS progression to a life threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS. PMID- 26889415 TI - TGF-beta-activated kinase-1: New insights into the mechanism of TGF-beta signaling and kidney disease. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates a wide variety of cellular functions, including cell growth, cellular differentiation, apoptosis, and wound healing. TGF-beta1, the prototype member of the TGF-beta superfamily, is well established as a central mediator of renal fibrosis. In chronic kidney disease, dysregulation of expression and activation of TGF-beta1 results in the relentless synthesis and accumulation of extracellular matrix proteins that lead to the development of glomerulosclerosis and tubulointerstitial fibrosis, and ultimately to end-stage renal disease. Therefore, specific targeting of the TGF-beta signaling pathway is seemingly an attractive molecular therapeutic strategy in chronic kidney disease. Accumulating evidence demonstrates that the multifunctionality of TGF-beta1 is connected with the complexity of its cell signaling networks. TGF-beta1 signals through the interaction of type I and type II receptors to activate distinct intracellular pathways. Although the Smad signaling pathway is known as a canonical pathway induced by TGF-beta1, and has been the focus of many previous reviews, importantly TGF-beta1 also induces various Smad-independent signaling pathways. In this review, we describe evidence that supports current insights into the mechanism and function of TGF-beta-activated kinase 1 (TAK1), which has emerged as a critical signaling molecule in TGF-beta-induced Smad-independent signaling pathways. We also discuss the functional role of TAK1 in mediating the profibrotic effects of TGF-beta1. PMID- 26889416 TI - Intravenous albumin for the prevention of contrast-induced nephropathy in patients with liver cirrhosis and chronic kidney disease undergoing contrast enhanced CT. AB - BACKGROUND: The purpose of this study was to evaluate the incidence of contrast induced nephropathy (CIN), and the effect of intravenous albumin for prophylaxis of CIN in patients with liver cirrhosis (LC) and chronic kidney disease (CKD). METHODS: We conducted a retrospective study of 81 subjects with LC and CKD (estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m(2)) who underwent contrast-enhanced computed tomography (CT). Patients received either isotonic sodium bicarbonate solution (3 mL/kg for 1 h before CT and 1 mL/kg/h for 6 h after CT) or albumin (20% albumin, 25 mL for 1 h before CT and 75 mL for 6 h after CT). CIN was defined as an increase of >=25% or >=0.5 mg/dL in serum creatinine level. RESULTS: Overall, CIN developed in three patients (3.7%). Of the 81 subjects, 43 received sodium bicarbonate solution and 38 received albumin. Both groups were comparable with regard to age, sex, diabetes mellitus, and baseline eGFR. The albumin group showed a significantly poorer liver function profile. CIN incidence did not differ significantly between the groups: it occurred in one (2.3%) of the 43 subjects receiving sodium bicarbonate and two (5.3%) of the 38 subjects receiving albumin (P=0.6). However, the albumin group showed a significantly smaller increase in body weight (P=0.03). CONCLUSION: The incidence of CIN in patients with LC and CKD undergoing contrast-enhanced CT after preventive measures was relatively low. The incidence of CIN was not significantly different between sodium bicarbonate and albumin groups. PMID- 26889419 TI - Consecutive episodes of peritonitis in a patient undergoing peritoneal dialysis caused by unusual organisms: Brevibacterium and Pantoea agglomerans. AB - A 52-year-old man undergoing continuous ambulatory peritoneal dialysis presented with two consecutive episodes of peritonitis caused by unusual organisms, namely, Brevibacterium and Pantoea agglomerans. The patient was successfully treated with a 2-week course of cefazolin and ceftazidime for the Brevibacterium-associated peritonitis, and a 3-week course of gentamicin for the P. agglomerans-associated peritonitis. Although these environmental organisms are rarely responsible for human infection, the number of reported cases of human infection by these unusual organisms has increased. This report emphasizes the potential for infection by environmental organisms in patients undergoing peritoneal dialysis. PMID- 26889421 TI - Hyperuricemia: A non-traditional risk factor for development and progression of chronic kidney disease? PMID- 26889420 TI - A case of biopsy-proven chronic kidney disease on progression from acute phosphate nephropathy. AB - Acute phosphate nephropathy (APhN) following oral sodium phosphate solution (OSP) ingestion as a bowel purgative has been frequently reported. It was recently suggested that APhN could progress to chronic kidney disease (CKD) and a history of APhN might be considered as one of the causes of CKD. However, there are few reports proving APhN as a cause of CKD. Here, we report a case of APhN that progressed to CKD, as proven by renal biopsy. PMID- 26889422 TI - Renal infarction caused by paradoxical embolism through a patent foramen ovale. AB - A 48-year-old man presented with acute right flank pain. A computed tomography scan revealed right renal infarction. Because he had no thrombosis in the renal vessels and no clear embolic source, a further examination was performed to find the cause of the renal infarction. On transesophageal echocardiography, a right to-left shunt during the Valsalva maneuver established a diagnosis of patent foramen ovale. This is a case of paradoxical embolism through a PFO leading to renal infarction. PMID- 26889424 TI - Risk factors for mortality in patients with acute kidney injury and hypotension treated with continuous veno-venous hemodiafiltration. AB - BACKGROUND: Continuous veno-venous hemodiafiltration (CVVHDF) is a preferred treatment modality in hemodynamically unstable acute kidney injury (AKI) patients, because it has advantages over intermittent dialysis in terms of hemodynamic stability. However, this patient group still shows a significantly high mortality rate. To aid in the management of these high-risk patients, we evaluated the risk factors for mortality in CVVHDF-treated hypotensive AKI patients. METHODS: We studied 67 patients with AKI and hypotension who were treated with CVVHDF from February 2008 to August 2010. We reviewed patient characteristics and laboratory parameters to evaluate the risk factors for 90-day mortality. RESULTS: Of the 67 enrolled patients (male:female=42:25; mean age=69+/ 14 years), 18 (27%) survived until 90 days after the initiation of CVVHDF. There was no significant difference in survival rates according to the etiology of AKI [hypovolemic shock 2/10 (20%), cardiogenic shock 4/20 (20%), septic shock 12/37 (32%)]. Univariate analysis did show significant differences between survivors and non-survivors in the frequency of ventilator use (44% vs. 76%, respectively; P=0.02), APACHE II score (29+/-7 vs. 34+/-7, respectively; P=0.01), SOFA score (11+/-4 vs. 13+/-4, respectively; P=0.03), blood pH (7.3+/-0.1 vs. 7.2+/-0.1, respectively; P=0.03), and rate of urine output <500 mL for 12 hours (50% vs. 80%, respectively; P=0.03). A multivariate Cox proportional hazards model showed that a urine output<500 mL for 12 hours was the only significant risk factor for 90-day mortality following CVVHDF treatment (odds ratio=2.1, confidence interval=1.01-4.4, P=0.048). CONCLUSION: A urine output<500 mL for 12 hours before the initiation of CVVHDF is an independent risk factor for 90-day mortality in hypotensive AKI patients treated with CVVHDF. PMID- 26889426 TI - Endothelium-dependent vasodilation by ferulic acid in aorta from chronic renal hypertensive rats. AB - BACKGROUND: Ferulic acid (FA) is a naturally occurring nutritional compound. Although it has been shown to have antihypertensive effects, its effects on vascular function have not been intensively established. The aim of this study was to assess the vasoreactivity of FA in chronic two-kidney, one-clip (2K1C) renal hypertensive rats. METHODS: Hypertension was induced in 2K1C rats by clipping the left renal artery and age-matched rats that received a sham treatment served as a control. Thoracic aortas were mounted in tissue baths to measure isometric tension. The effects of FA on vasodilatory responses were evaluated based on contractile responses induced by phenylephrine in the aortic rings obtained from both 2K1C and sham rats. Basal nitric oxide (NO) bioavailability in the aorta was determined by the contractile response induced by NO synthase inhibitor N (G)-nitro-l-arginine methyl ester (l-NAME). RESULTS: FA induced concentration-dependent relaxation responses which were greater in 2K1C hypertensive rats than in sham-clipped control rats. This relaxation induced by FA was partially blocked by the removal of endothelium or by pretreating with l-NAME. l-NAME-induced contractile responses were augmented by FA in 2K1C rats, while no significant differences were noted in sham rats. FA improved acetylcholine-induced endothelium-dependent vasodilation in 2K1C rats, but not in sham rats. The simultaneous addition of hydroxyhydroquinone significantly inhibited the increase in acetylcholine-induced vasodilation by FA. CONCLUSION: These results suggest that FA restores endothelial function by altering the bioavailability of NO in 2K1C hypertensive rats. The results explain, in part, the mechanism underlying the vascular effects of FA in chronic renal hypertension. PMID- 26889425 TI - Incidence of post-transplant glomerulonephritis and its impact on graft outcome. AB - BACKGROUND: Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN. METHODS: Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study. RESULTS: The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors. CONCLUSION: We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or de novo GN should be the critical focus of post-transplant care. PMID- 26889423 TI - Permeability factors in nephrotic syndrome and focal segmental glomerulosclerosis. AB - Circulating permeability factors have been identified in the plasma of patients with focal segmental glomerulosclerosis (FSGS). Post-transplant recurrence of proteinuria, improvement of proteinuria after treatment with plasmapheresis, and induction of proteinuria in experimental animals by plasma fractions each provide evidence for such plasma factors. Advanced proteomic methods have identified candidate molecules in recurrent FSGS. We have proposed cardiotrophin-like cytokine-1 as an active factor in FSGS. Another potential permeability factor in FSGS is soluble urokinase receptor. In our studies, in vitro plasma permeability activity is blocked by substances that may decrease active molecules or block their effects. We have shown that the simple sugar galactose blocks the effect of FSGS serum in vitro and decreases permeability activity when administered to patients. Since the identities of permeability factors and their mechanisms of action are not well defined, treatment of FSGS is empiric. Corticosteroids are the most common agents for initial treatment. Calcineurin inhibitors, such as cyclosporine A, and tacrolimus and immunosuppressive medications, including mycophenylate, induce remission is some patients with steroid-resistant or dependent nephrotic syndrome. Therapies that diminish proteinuria and slow progression in FSGS as well as other conditions include renin-angiotensin blockade, blood pressure lowering and plasma lipid control. Use of findings from in vitro studies, coupled with definitive identification of pathogenic molecules, may lead to new treatments to arrest FSGS progression and prevent recurrence after transplantation. PMID- 26889427 TI - Impact of gene polymorphisms of interleukin-18, transforming growth factor-beta, and vascular endothelial growth factor on development of IgA nephropathy and thin glomerular basement membrane disease. AB - BACKGROUND: We investigated the effects of gene polymorphisms on the development of IgA nephropathy and thin glomerular basement membrane (GBM) disease by analyzing polymorphisms in the interleukin (IL)-18, transforming growth factor (TGF)-beta, and vascular endothelial growth factor (VEGF) genes in Korean patients. METHODS: This study included 146 normal individuals and 69 biopsy proven IgA nephropathy and 44 thin GBM disease patients. The gene polymorphisms 607 A/C and -137 G/C in IL-18, -509C/T and T869C in TGF-beta, and -2578C/A and 405C/G in VEGF were investigated in DNA extracted from peripheral blood. RESULTS: The frequencies of the IL-18 -607CC genotype (43.5% vs. 21.2%, P=0.002, P corrected=0.012) and the VEGF 405 GG genotype (37.7% vs. 21.2%, P=0.002, P corrected=0.012) were significantly increased in the IgA nephropathy group compared with the control group, whereas no significant differences in genotype frequency were observed between the thin GBM disease and control groups. However, there were no significant differences in genotype and allele frequencies between the IgA nephropathy and thin GBM disease groups. CONCLUSION: This study did not show any statistically significant differences of six selected gene polymorphisms of the IL-18, TGF-beta, and VEGF genes between IgA nephropathy and thin GBM disease. Additional extensive studies are required to clarify the potential role of gene polymorphism to discriminate IgA nephropathy and thin GBM disease without renal biopsy. PMID- 26889428 TI - Renal artery thrombosis secondary to sepsis-induced disseminated intravascular coagulation in acute pyelonephritis. AB - There are some reports of renal vein thrombosis associated with acute pyelonephritis, but a case of renal artery thrombosis in acute pyelonephritis has not been reported yet. Here we report a case of renal artery thrombosis which developed in a patient with acute pyelonephritis complicated with sepsis-induced disseminated intravascular coagulation (DIC). A 65-year-old woman with diabetes was diagnosed with acute pyelonephritis complicated with sepsis. Escherichia coli was isolated from both blood and urine cultures. When treated with antibiotics, her condition gradually improved. She suddenly complained of severe right flank pain without fever in the recovery phase. A computed tomography scan revealed right renal artery thrombosis with concomitant renal infarction. Prophylactic anticoagulation therapy was not suggested because of sustained thrombocytopenia and increased risk of bleeding. Flank pain resolved with conservative treatment and perfusion of infarcted kidney improved at the time of discharge. To our knowledge, this is the first case of renal artery thrombosis related to acute pyelonephritis with sepsis-induced DIC. PMID- 26889429 TI - Bilateral gluteal compartment syndrome complicated by rhabdomyolysis and acute kidney injury in a patient with alcohol intoxication. AB - Bilateral gluteal compartment syndrome is a rare clinical entity that can be complicated by rhabdomyolysis or acute kidney injury (AKI). We report the a case of a 30-year-old woman without any comorbid diseases who was diagnosed with bilateral gluteal compartment syndrome complicated by rhabdomyolysis and dialysis requiring AKI, which was caused by prolonged immobilization under the influence of alcohol. Although the patient's renal function recovered fully after 5 sessions of hemodialysis, sciatic neuropathy caused by gluteal compartment syndrome led to permanent foot drop. PMID- 26889430 TI - Acute oxalate nephropathy caused by ethylene glycol poisoning. AB - Ethylene glycol (EG) is a sweet-tasting, odorless organic solvent found in many agents, such as anti-freeze. EG is composed of four organic acids: glycoaldehyde, glycolic acid, glyoxylic acid and oxalic acid in vivo. These metabolites are cellular toxins that can cause cardio-pulmonary failure, life-threatening metabolic acidosis, central nervous system depression, and kidney injury. Oxalic acid is the end product of EG, which can precipitate to crystals of calcium oxalate monohydrate in the tubular lumen and has been linked to acute kidney injury. We report a case of EG-induced oxalate nephropathy, with the diagnosis confirmed by kidney biopsy, which showed acute tubular injury of the kidneys with extensive intracellular and intraluminal calcium oxalate monohydrate crystal depositions. PMID- 26889431 TI - Niacin in patients with chronic kidney disease: Is it effective and safe? PMID- 26889432 TI - Effect of intradialytic change in blood pressure and ultrafiltration volume on the variation in access flow measured by ultrasound dilution. AB - BACKGROUND: Prospective access flow measurement is the preferred method for vascular access surveillance in hemodialysis (HD) patients. We studied the effect of intradialytic change in blood pressure and ultrafiltration volume on the variation in access flow measured by ultrasound dilution. METHODS: Access flow was measured 30 minutes, 120 minutes, and 240 minutes after the start of HD by ultrasound dilution in 30 patients during 89 HD sessions and evaluated for variation. RESULTS: The mean age of the 30 patients was 62+/-11 years: 19 were male. The accesses comprised 16 fistulae and 14 grafts. The mean access flow over all sessions decreased by 6.1% over time (1265+/-568 mL/min after 30 minutes, 1260+/-599 mL/min after 120 minutes, and 1197+/-576 mL/min after 240 minutes, P<0.01 by repeated measures ANOVA). In addition, a>=5% decrease in mean arterial pressure during HD significantly reduced access flow (P=0.014). However, no other variable (ultrafiltration volume, sex, age, presence of diabetes, type or location of access, body surface area, hemoglobin, serum albumin level) interacted significantly with the effect of time on access flow. Furthermore, mean arterial pressure did not correlate with ultrafiltration volume. CONCLUSION: We conclude that the variation in access flow during HD is relatively small. Decreased blood pressure is a risk factor for variation in access flow measured by ultrasound dilution. In most patients whose blood pressures are stable during HD, the access flow can be measured at any time during the HD treatment. PMID- 26889433 TI - Effects of low-dose niacin on dyslipidemia and serum phosphorus in patients with chronic kidney disease. AB - BACKGROUND: Niacin supplementation improves dyslipidemia and lowers serum phosphorus levels in patients with chronic kidney disease (CKD). We evaluated whether low-dose niacin supplementation can improve dyslipidemia, lower serum phosphorus levels, and be administered with a low frequency of adverse effects in patients with CKD. METHODS: We retrospectively analyzed the clinical records of patients with CKD who had taken niacin from January 2009 to June 2011. We excluded patients with CKD stage 1 and 5. We then enrolled 31 patients with CKD who had taken niacin at a fixed dose of 500 mg/day for 6 months. We also randomly selected 30 patients with CKD who had been taking statin for 9 months as a control group. RESULTS: Among the 34 patients with CKD who were prescribed niacin, five (14%) complained of adverse effects, and three (8%) discontinued niacin. The proportion of patients in the niacin group who had been taking a statin or omega-3 fatty acids was 67.7% and 48.8%, respectively. In the niacin group, high-density lipoprotein cholesterol level was significantly increased and triglyceride level was significantly decreased at 12 and 24 weeks compared with baseline levels (P<0.05). In the niacin group, phosphorous level (P<0.05) was significantly decreased, and glomerular filtration rate (GFR) was significantly increased (P<0.05) at 24 weeks compared with baseline values. CONCLUSION: Low dose niacin had a low frequency of adverse effects and also improved dyslipidemia, lowered serum phosphorus level, and increased GFR in patients with CKD. Further studies are needed to evaluate the long-term effects of low-dose niacin for renal progression of CKD. PMID- 26889434 TI - Clostridium difficile-associated diarrhea in dialysis patients. AB - BACKGROUND: Dialysis patients have impaired host defense mechanisms and frequently require antibiotics for various infective complications. In this study, we investigated whether dialysis patients have greater risk for Clostridium difficile-associated diarrhea (CDAD). METHODS: During the 4-year study period (2004-2008), 85 patients with CDAD were identified based on a retrospective review of C difficile toxin assay or histology records. Nosocomial diarrheal patients without CDAD were considered as controls (n=403). We assessed the association between renal function and the prevalence and clinical outcomes of CDAD. RESULTS: There was a significant difference in the prevalence rate of chronic kidney disease (CKD) between CDAD and non-CDAD patients (P<0.001). Sixteen patients (18.8%) of the CDAD group were treated with dialysis, whereas 21 patients (5.2%) of the non-CDAD group were treated with dialysis. There was a significant association between renal function and CDAD in patients on dialysis [odds ratio (OR)=4.44, 95% confidence interval (CI) 2.19-8.99, P<0.001], but not in patients with CKD stage 3-5 (OR=1.10, 95% CI 0.63-1.92, P=0.73). In multivariate analysis, CKD stage 5D was an independent risk factor for the development of CDAD (OR=13.36, 95% CI 2.94-60.67, P=0.001). CONCLUSION: Our data indicate that dialysis patients might be at a greater risk of developing CDAD, which suggests that particular attention should be provided to CDAD when antibiotic treatment is administered to dialysis patients. PMID- 26889435 TI - Correlation between peripheral venous and arterial blood gas measurements in patients admitted to the intensive care unit: A single-center study. AB - BACKGROUND: The objective of this study was to examine the correlation between arterial blood gas (ABG) and peripheral venous blood gas (VBG) samples for all commonly used parameters in patients admitted to a medical intensive care unit (ICU). METHODS: A single-center, prospective trial was carried out in a medical ICU in order to determine the level of correlation of ABG and peripheral VBG measurements. A maximum of five paired ABG-VBG samples were obtained per patient to prevent a single patient from dominating the data set. RESULTS: Regression equations were derived to predict arterial values from venous values as follows: arterial pH=-1.108+1.145*venous pH+0.008*PCO2-0.012*venous HCO3+0.002*venous total CO2 (R(2)=0.655), arterial PCO2=88.6-10.888*venous pH+0.150*PCO2+0.812*venous HCO3+0.124*venous total CO2 (R(2)=0.609), arterial HCO3=-89.266+12.677*venous pH+0.042*PCO2+0.675*venous HCO3+0.185*venous total CO2 (R(2)=0.782). The mean ABG minus peripheral VBG differences for pH, PCO2, and bicarbonates were not clinically important for between-person heterogeneity. CONCLUSION: Peripheral venous pH, PCO2, bicarbonates, and total CO2 may be used as alternatives to their arterial equivalents in many clinical contexts encountered in the ICU. PMID- 26889436 TI - A case of membranous nephropathy as a manifestation of graft-versus-host disease. AB - Nephrotic syndrome (NS) rarely occurs after hematopoietic stem cell transplantation (HSCT) as a late manifestation of graft-versus-host disease (GVHD). Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD. PMID- 26889438 TI - Sulodexide in IgA nephropathy. PMID- 26889437 TI - Association of acute tubular necrosis with gross hematuria in cirrhosis-related immunoglobulin A nephropathy. AB - Immunoglobulin A (IgA) nephropathy associated with cirrhosis is the most common form of secondary IgA nephropathy (IgAN). Cirrhosis-related IgAN is usually clinically silent with a rare occurrence of gross hematuria, unlike in cases of idiopathic IgAN. Especially, acute tubular necrosis (ATN) associated with gross hematuria is very rare in cirrhosis-related IgAN, although acute renal failure is a frequently reported complication in advanced cirrhosis. Herein, we report an unusual case of ATN requiring renal replacement therapy, associated with gross hematuria in a patient with nonalcoholic, hepatitis B virus-associated cirrhosis. Results of a histopathological analysis revealed obstruction of the lumen of renal tubules by red blood cell casts, a marked tubular necrosis, and IgA deposition in the mesangium. The patient's renal function and gross hematuria were clearly improved after lamivudine treatment. PMID- 26889439 TI - The Role of Minimally Invasive Plate Osteosynthesis in Rib Fixation: A Review. AB - More than a century ago, the first scientific report was published about fracture fixation with plates. During the 1950's, open reduction and plate fixation for fractures were standardized by the founders of Arbeitsgemeinschaft fur osteosynthesefragen/Association for the Study of Internal Fixation. Since the introduction of plate fixation for fractures, several plates and screws have been developed, all with their own characteristics. To accomplice more fracture stability, it was thought the bigger the plate, the better. The counter side was a compromised blood supply of the bone, often resulting in bone necrosis and ultimately delayed or non-union. With the search and development of new materials and techniques for fracture fixation, less invasive procedures have become increasingly popular. This resulted in the minimally invasive plate osteosynthesis (MIPO) technique for fracture fixation. With the MIPO technique, procedures could be performed with smaller incisions and thus with less soft tissue damage and a better preserved blood supply. The last 5 years rib fixation has become increasingly popular, rising evidence has become available suggesting that surgical rib fixation improves outcome of patients with a flail chest or isolated rib fractures. Many surgical approaches for rib fixation have been described in the old literature, however, most of these techniques are obscure nowadays. Currently mostly large incisions with considerable surgical insult are used to stabilize rib fractures. We think that MIPO deserves a place in the surgical treatment of rib fractures. We present the aspects of diagnosis, preoperative planning and operative techniques in regard to MIPO rib fixation. PMID- 26889440 TI - Repair of Tetralogy of Fallot in Infancy via the Atrioventricular Approach. AB - BACKGROUND: Tetralogy of Fallot (TOF) is a well-recognized congenital heart disease. Despite improvements in the outcomes of surgical repair, the optimal timing of surgery and type of surgical management of patients with TOF remains controversial. The purpose of this study was to assess outcomes following the repair of TOF in infants depending on the surgical procedure used. METHODS: This study involved the retrospective review of 120 patients who underwent TOF repair between 2010 and 2013. Patients were divided into three groups depending on the surgical procedure that they underwent. Corrective surgery was done via the transventricular approach (n=40), the transatrial approach (n=40), or a combined atrioventricular approach (n=40). Demographic data and the outcomes of the surgical procedures were compared among the groups. RESULTS: In the atrioventricular group, the incidence of the following complications was found to be significantly lower than in the other groups: complete heart block (p=0.034), right ventricular failure (p=0.027) and mediastinal bleeding (p=0.007). Patients in the atrioventricular group had a better postoperative right ventricular ejection fraction (p=0.001). No statistically significant differences were observed among the three surgical groups in the occurrence of tachycardia, renal failure, and tricuspid incompetence. The one-year survival rates in the three groups were 95%, 90%, and 97.5%, respectively (p=0.395). CONCLUSION: Combined atrioventricular repair of TOF in infancy can be safely performed, with acceptable surgical risk, a low incidence of reoperation, good ventricular function outcomes, and an excellent survival rate. PMID- 26889441 TI - The Risk Factors and Outcomes of Acute Kidney Injury after Thoracic Endovascular Aortic Repair. AB - BACKGROUND: We aimed to evaluate the incidence, predictive factors, and impact of acute kidney injury (AKI) after thoracic endovascular aortic repair (TEVAR). METHODS: A total of 53 patients who underwent 57 TEVAR operations between 2008 and 2015 were reviewed for the incidence of AKI as defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease risk) consensus criteria. The estimated glomerular filtration rate was determined in the perioperative period. Comorbidities and postoperative outcomes were retrospectively reviewed. RESULTS: Underlying aortic pathologies included 21 degenerative aortic aneurysms, 20 blunt traumatic aortic injuries, six type B aortic dissections, five type B intramural hematomas, three endoleaks and two miscellaneous diseases. The mean age of the patients was 61.2+/-17.5 years (range, 15 to 85 years). AKI was identified in 13 (22.8%) of 57 patients. There was an association of preoperative stroke and postoperative paraparesis and paraplegia with AKI. The average intensive care unit (ICU) stay in patients with AKI was significantly longer than in patients without AKI (5.3 vs. 12.7 days, p=0.017). The 30-day mortality rate in patients with AKI was significantly higher than patients without AKI (23.1% vs. 4.5%, p=0.038); however, AKI did not impact long-term survival. CONCLUSION: Preoperative stroke and postoperative paraparesis and paraplegia were identified as predictors for AKI. Patients with AKI experienced longer average ICU stays and greater 30-day mortality than those without AKI. Perioperative identification of high-risk patients, as well as nephroprotective strategies to reduce the incidence of AKI, should be considered as important aspects of a successful TEVAR procedure. PMID- 26889442 TI - Selective Carotid Shunting Based on Intraoperative Transcranial Doppler Imaging during Carotid Endarterectomy: A Retrospective Single-Center Review. AB - BACKGROUND: Carotid endarterectomy (CEA) with selective shunting is the surgical method currently used to treat patients with carotid artery disease. We evaluated the incidence of major postoperative complications in patients who underwent CEA with selective shunting under transcranial Doppler (TCD) at our institution. METHODS: The records of 45 patients who underwent CEA with TCD-based selective shunting under general anesthesia from November 2009 to June 2015 were reviewed. The risk factors for postoperative complications were analyzed using univariate and multivariate analysis. RESULTS: Preoperative atrial fibrillation was observed in three patients. Plaque ulceration was detected in 10 patients (22.2%) by preoperative computed tomography imaging. High-level stenosis was observed in 16 patients (35.5%), and 18 patients had contralateral stenosis. Twenty patients (44.4%) required shunt placement due to reduced TCD flow or a poor temporal window. The 30-day mortality rate was 2.2%. No cases of major stroke were observed in the 30 days after surgery, but four cases of minor stroke were noted. Univariate analysis showed that preoperative atrial fibrillation (odds ratio [OR], 40; p=0.018) and ex-smoker status (OR, 17.5; p=0.021) were statistically significant risk factors for a minor stroke in the 30-day postoperative period. Analogously, multivariate analysis also found that atrial fibrillation (p<0.001) and ex-smoker status (p=0.002) were significant risk factors for a minor stroke in the 30-day postoperative period. No variables were identified as risk factors for 30-day major stroke or death. No wound complications were found, although one (2.2%) of the patients suffered from a hypoglossal nerve injury. CONCLUSION: TCD based CEA is a safe and reliable method to treat patients with carotid artery disease. Preoperative atrial fibrillation and ex-smoker status were found to increase the postoperative risk of a small embolism leading to a minor neurologic deficit. PMID- 26889443 TI - Pectus Excavatum and Pectus Carinatum: Associated Conditions, Family History, and Postoperative Patient Satisfaction. AB - BACKGROUND: Pectus excavatum (PE) and pectus carinatum (PC) are the most common chest wall deformities. In this study, we aimed to characterize how patients obtained information about these deformities, as well as patients' family history, associated medical problems, and postoperative satisfaction after the Nuss and Abramson procedures. METHODS: This cross-sectional retrospective study included patients who were operated by a single surgeon between 2006 and 2013. Follow-up calls were made after approval of our institution's ethics committee. We reached 207 of the 336 PE patients (61.6%) and 73 of the 96 PC patients (76%). RESULTS: The majority of the patients were male (85% of the PE patients and 91.8% of the PC patients). The age of diagnosis of PE was 14.52+/-0.51 years and the age at the time of operation was 17.89+/-0.42 years; for PC patients, the corresponding ages were 15.23+/-0.55 years and 16.77+/-0.55 years, respectively. A total of 70% of the PE patients and 63.8% of the PC patients obtained information about pectus deformities through the Internet. In 27.1% of the PE patients with an associated anomaly, 57.1% (n=13) had scoliosis, while 41.1% of the PC patients with an associated anomaly had kyphosis (n=5). Postoperative satisfaction, as evaluated on a scale from 0 to 10, was 8.17+/-0.15 for PE patients and 8.37+/-0.26 for PC patients. The postoperative pain duration was 51.93+/-5.18 days for PE patients and 38.5+/-6.88 days for PC patients. CONCLUSION: In this study, we found that most patients with pectus deformities were male. The Internet was an important resource for patients to learn about their deformities. Family history and associated anomalies were identified as important aspects for consideration in the clinical setting. The patients reported high levels of postoperative satisfaction, and pain management was found to be one of the most important elements of postoperative care. PMID- 26889444 TI - Tricuspid Valve Re-Repair in Ebstein Anomaly Using the Cone Technique. AB - The management of recurrent tricuspid regurgitation after tricuspid valve repair in patients with Ebstein anomaly is difficult, and tricuspid valve replacement is most commonly performed in such patients. We report two cases of recurrent tricuspid regurgitation in patients with Ebstein anomaly that were successfully re-repaired using the cone technique. The cone repair technique is a useful surgical method for reconstructing a competent tricuspid valve, and can be applied in patients who have undergone previous tricuspid valve repair. PMID- 26889446 TI - Organizing Thrombus Mimicking a Cardiac Tumor Located at the Mitral-Aortic Intervalvular Fibrosa. AB - Thrombosis at the left ventricular outflow tract occurs without any detectable heart disease or predisposing factors only extremely rarely. A 48-year-old male visited Konkuk University Medical Center with loss of consciousness one month prior to presentation. Before he visited our hospital, he had been diagnosed with a cardiac tumor, which was located between the left atrium and posterior aortic root, and which was adjacent to both the aortic and mitral valves. Cardiac transplantation was recommended at the other hospital because of the high risk of cardiac dysfunction induced by both aortic and mitral valvular dysfunction after surgical resection. Based on preoperative transthoracic echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, and intra-operative transesophageal echocardiography, we considered it to be a benign tumor. Complete resection was achieved and the pathology confirmed organizing thrombus. We report a case of organizing thrombus mimicking a cardiac tumor, which was located at the mitral-aortic intervalvular fibrosa of the left ventricular outflow tract without any heart disease. PMID- 26889445 TI - Persistent Fifth Aortic Arch with Coarctation. AB - Persistent fifth aortic arch (PFAA) is a rare congenital anomaly of the aortic arch frequently associated with other cardiovascular anomalies, such as tetralogy of Fallot and aortic arch coarctation or interruption. We report the case of a neonate with PFAA with coarctation who successfully underwent surgical repair. PMID- 26889447 TI - Modified Surgical Intervention for Extensive Mitral Valve Endocarditis and Posterior Mitral Annular Calcification. AB - The concomitant presence of posterior mitral annular calcification and infectious mitral valve lesions poses a technical challenge with considerable perioperative risk when using previously proposed techniques for mitral valve surgery. Herein, we report a case of the use of a modified surgical technique to successfully treat a patient with mitral infective endocarditis complicated by a subendocardial abscess and extensive posterior mitral annular calcification. PMID- 26889448 TI - A Case of Recurrent Aortic Rupture Associated with Klebsiella pneumoniae Pericarditis Treated by Two Separate Aortic Operations. AB - A 49-year-old female presented with severe dyspnea. She was diagnosed with cardiac tamponade combined with ascending aortic pseudoaneurysm and rupture, which was caused by Klebsiella pneumoniae infection. This extremely rare condition was managed by an emergency pericardiostomy and two separate aortic operations. Antibiotics active for the K. pneumoniae isolate were used throughout. The patient was well for nine months after discharge and continues to be followed up for signs of possible reinfection. PMID- 26889449 TI - Surgical Management of Aorto-Esophageal Fistula as a Late Complication after Graft Replacement for Acute Aortic Dissection. AB - A 49-year-old male presented with chills and a fever. Five years previously, he underwent ascending aorta and aortic arch replacement using the elephant trunk technique for DeBakey type 1 aortic dissection. The preoperative evaluation found an esophago-paraprosthetic fistula between the prosthetic graft and the esophagus. Multiple-stage surgery was performed with appropriate antibiotic and antifungal management. First, we performed esophageal exclusion and drainage of the perigraft abscess. Second, we removed the previous graft, debrided the abscess, and performed an in situ re-replacement of the ascending aorta, aortic arch, and proximal descending thoracic aorta, with separate replacement of the innominate artery, left common carotid artery, and extra-anatomical bypass of the left subclavian artery. Finally, staged esophageal reconstruction was performed via transthoracic anastomosis. The patient's postoperative course was unremarkable and the patient has done well without dietary problems or recurrent infections over one and a half years of follow-up. PMID- 26889450 TI - Diaphragm Translocation as Surgical Treatment for Agenesis of the Right Lung and Secondary Tracheal Compression. AB - A 12-month-old boy was diagnosed with agenesis of the right lung. Mediastinal deviation progressed to the diseased side as the patient matured; therefore, tracheal distortion developed. As a result, tracheal compression developed between the vertebral body and aorta. The patient was repeatedly admitted to the hospital because of recurrent pulmonary infection and combined severe respiratory distress. Diaphragm translocation was performed to treat the patient. The postoperative course was favorable, and computed tomography scan findings and symptoms had improved at 1 year after surgery. PMID- 26889451 TI - Malignant Schwannoma of the Esophagus: A Rare Case Report. AB - Neurogenic tumors are the most prevalent tumors of the mediastinum, and schwannomas are the most common type of neurogenic tumor. Primary neurogenic neoplasm of the esophagus is uncommon and malignant schwannoma of the esophagus is extremely rare. We report a case of a 27-year-old female presenting with dysphagia and palpitations who was found to have a lobulated tumor in the mediastinum that was compressing the esophageal lumen. The tumor was successfully treated surgically without recurrence. The final diagnosis, on histopathological examination of the specimen, was malignant schwannoma. PMID- 26889452 TI - Nodular Fasciitis of the Chest in a Young Woman. AB - Nodular fasciitis is a benign reactive proliferation that usually involves the deep fascia. Although it is relatively common in the adult population, it is often misdiagnosed as sarcoma due to its rapid growth and pathological features. It rarely presents as a chest wall tumor in young patients. Here, we report a case of nodular fasciitis involving the chest wall of an 18-year-old woman and its surgical management. This case underscores the need to consider nodular fasciitis in the differential diagnosis of chest wall tumors in young patients. PMID- 26889453 TI - Single-Suture Neochorda-Folding Plasty for Mitral Regurgitation. AB - The single-suture neochorda-folding plasty technique is a modification of existing mitral valve repair techniques. In the authors' experience, its simplicity, reliability, and versatility make it a useful technique for mitral valve repair, especially when a minimally invasive approach is used. PMID- 26889454 TI - Changes of High Sensitivity C-Reactive Protein During Clopidogrel Therapy in Patients Undergoing Percutaneous Coronary Intervention. AB - BACKGROUND: The crucial role of inflammation in the development and progression of atherosclerosis has been previously described. However, there is insufficient data available to demonstrate the changes in high sensitivity C-reactive protein (hs-CRP) during clopidogrel therapy. OBJECTIVES: In the present study, we aimed to assess the changes in the inflammatory marker of coronary heart disease, i.e., hs-CRP during clopidogrel therapy, in patients undergoing percutaneous coronary intervention (PCI). We also evaluated the anti-inflammatory effects of clopidogrel, if any, in different groups of patients. PATIENTS AND METHODS: The study population included 650 consecutive patients who underwent elective, urgent, or emergent PCI. Patients received a 300-mg loading dose of clopidogrel (Plavix((r))) and aspirin either 24 hours before the planned PCI, or immediately before the procedure in patients with urgent or emergent PCI, followed by a 75-mg daily maintenance dose for up to 12 weeks. At the end of the 12(th) week, hs-CRP was re-assessed. RESULTS: Six hundred-fifty patients including 386 (59.4%) male and 264 (40.6%) female subjects were enrolled in the study. The mean hs-CRP level was 15.36 +/- 9.83 mg/L with a median of 14 mg/L (interquartile range 8 to 19.6 mg/L). Female, hypertensive, diabetic, and non-smoking patients had higher reductions in hs-CRP in response to clopidogrel therapy compared to male, non hypertensive, non-diabetic and smoker patients, respectively (all P < 0.005). The changes in the hs-CRP levels were also statistically different in patients with various index events before PCI (P < 0.001). No significant differences were observed in the mean reduction of hs-CRP between the patients without stent implantation and those with bare metal or drug-eluting stents (P = 0.07), respectively. CONCLUSIONS: We found that the use of clopidogrel in patients undergoing PCI had favorable effects on the suppression of hs-CRP. This effect appears to be heightened and more apparent in some group of patients with co morbidities such as diabetes and hypertension. PMID- 26889456 TI - Oral L-Arginine Administration Improves Anthropometric and Biochemical Indices Associated With Cardiovascular Diseases in Obese Patients: A Randomized, Single Blind Placebo Controlled Clinical Trial. AB - BACKGROUND: Recently, the potential of L-arginine supplementation as a novel and effective strategy for weight loss and improving biochemical parameters in obese patients has been under consideration. OBJECTIVES: To evaluate the influence of 8 week oral L-arginine supplementation on body mass index (BMI), waist circumference (WC), triceps skinfold (TS), subscapular skinfold (SS), systolic blood pressure (SBP), diastolic blood pressure (DBP), plasma fasting blood sugar (FBS), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and malondialdehyde (MDA) in patients with BMI values > 29.9 or visceral obesity (WC > 102 cm in men or > 88 cm in women). PATIENTS AND METHODS: Ninety obese patients were included in a single-blind randomized controlled trial. Patients were randomized to receive either L-arginine (3 or 6 g thrice daily) or placebo for 8 weeks. Anthropometric and biochemical indices, dietary intake, and blood pressure values were measured at the baseline and after the 8-week intervention. RESULTS: Significant decreases in anthropometric parameters, blood pressure (SBP, DBP), FBS, HbA1c, LDL, MDA (P < 0.001), TG (P = 0.02), and TC (P = 0.002) and a significant increase in HDL (P < 0.001) were observed in the intervention group, compared to the control group. In the control group, no significant differences were found between the baseline and end-of-intervention measurements. CONCLUSIONS: In conclusion, oral L-Arginine supplementation appears to improve anthropometric parameters, blood pressure values, and some blood biochemical indices associated with cardiovascular disease prevention. PMID- 26889455 TI - Comparison of Gated SPECT Myocardial Perfusion Imaging with Echocardiography for the Measurement of Left Ventricular Volumes and Ejection Fraction in Patients With Severe Heart Failure. AB - BACKGROUND: Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is known as a feasible tool for the measurement of left ventricular ejection fraction (EF) and volumes, which are of great importance in the management and follow-up of patients with coronary artery diseases. However, considering the technical shortcomings of SPECT in the presence of perfusion defect, the accuracy of this method in heart failure patients is still controversial. OBJECTIVES: The aim of the present study was to compare the results from gated SPECT MPI with those from echocardiography in heart failure patients to compare echocardiographically-derived left ventricular dimension and function data to those from gated SPECT MPI in heart failure patients. PATIENTS AND METHODS: Forty-one patients with severely reduced left ventricular systolic function (EF <= 35%) who were referred for gated SPECT MPI were prospectively enrolled. Quantification of EF, end-diastolic volume (EDV), and end-systolic volume (ESV) was performed by using quantitative gated spect (QGS) (QGS, version 0.4, May 2009) and emory cardiac toolbox (ECTb) (ECTb, revision 1.0, copyright 2007) software packages. EF, EDV, and ESV were also measured with two-dimensional echocardiography within 3 days after MPI. RESULTS: A good correlation was found between echocardiographically-derived EF, EDV, and ESV and the values derived using QGS (r = 0.67, r = 0.78, and r = 0.80 for EF, EDV, and ESV, respectively; P < 0.001) and ECTb (r = 0.68, 0.79, and r = 0.80 for EF, EDV, and ESV, respectively; P < 0.001). However, Bland-Altman plots indicated significantly different mean values for EF, 11.4 and 20.9 using QGS and ECTb, respectively, as compared with echocardiography. ECTb-derived EDV was also significantly higher than the EDV measured with echocardiography and QGS. The highest correlation between echocardiography and gated SPECT MPI was found for mean values of ESV different. CONCLUSIONS: Gated SPECT MPI has a good correlation with echocardiography for the measurement of left ventricular EF, EDV, and ESV in patients with severe heart failure. However, the absolute values of these functional parameters from echocardiography and gated SPECT MPI measured with different software packages should not be used interchangeably. PMID- 26889457 TI - Conduction Disorders in Continuous Versus Interrupted Suturing Technique in Ventricular Septal Defect Surgical Repair. AB - BACKGROUND: Ventricular septal defects (VSD) is one of the most frequent congenital cardiac malformations and cardiac conduction disorders are still one of the serious postoperative complications in this surgery. OBJECTIVES: This study aimed to compare the incidence of conduction disorders with the use of continuous compared to interrupted suturing techniques in VSD surgical repair. PATIENTS AND METHODS: Previously recorded data of 231 patients who underwent surgical closure of VSD between January 2009 and January 2012 at the Rajaie cardiovascular medical and research center were retrospectively reviewed. VSD surgical repair was performed using continues suturing technique in group A patients (n = 163, 70.6%) and interrupted suturing technique in group B patients (n = 68, 29.4%). RESULTS: The most common concomitant congenital anomaly was Tetralogy of Fallot (27.3%). Twenty-four (10.4%) patients had intraoperative cardiac arrhythmia, including 19 (8.2%) transient and 5 (2.2 %) permanent arrhythmia. During their ICU stay, ventricular arrhythmia and complete heart block were observed in 34 (14.7%) and 5 patients (2.2%), respectively. At the time of the last follow-up, incomplete right bundle branch block (RBBB), complete RBBB, RBBB with left anterior hemi-block, and complete heart block were identified in 84 (36.4%), 42 (18.2%), 29 (12.6%), and 5 patients (2.2%), respectively. The results revealed that group A patients were most likely to have had cardiac arrhythmias during their ICU stay and at the time of last follow-up (P < 0.001), while the intraoperative incidence of cardiac arrhythmia during surgery was not statistically significant between the two groups (P = 0.06). CONCLUSIONS: In the absence of any statistical differences in the other risk factors between the two groups, the difference in the incidence of conduction disorders can be attributed to the type of suturing used during the procedure. PMID- 26889458 TI - Coronary Slow Flow Phenomenon Clinical Findings and Predictors. AB - BACKGROUND: In some patients with chest pain, selective coronary angiography reveals slow contrast agent passage through the epicardial coronary arteries in the absence of stenosis. This phenomenon has been designated the slow coronary flow (SCF) phenomenon. OBJECTIVES: In this study, we aimed to describe the demographic and clinical findings and presence of common atherosclerosis risk factors in patients with the SCF phenomenon. PATIENTS AND METHODS: Between October 2014 and March 2015, demographic data, clinical histories, atherosclerosis risk factors, and laboratory and angiographic findings were recorded for all consecutive patients scheduled for coronary angiography and diagnosed with the SCF phenomenon, as well as a control group (patients with normal epicardial coronary arteries; NECA). SCF was diagnosed based on the thrombolysis in myocardial infarction frame count (TFC). A TFC > 27 indicated a diagnosis of SCF phenomenon. RESULTS: Among the 3600 patients scheduled for selective coronary angiography, 75 (2%) met the SCF criteria. SCF and NECA patients did not exhibit statistically significant differences in traditional risk factors except for hypertension, which was more prevalent in SCF than NECA patients (52% versus 31%, P = 0.008). A multivariable analysis indicated a low body mass index, presence of hypertension, low high-density lipoprotein cholesterol (HDL-c) level, and high hemoglobin level as independent predictors of the SCF phenomenon; of these, hypertension was the strongest predictor (odds ratio = 6.3, 95% confidence interval: 2.2 - 17.9, P = 0.001). CONCLUSIONS: The SCF phenomenon is relatively frequent, particularly among patients with acute coronary syndrome who are scheduled for coronary angiography. Hypertension, a low HDL-c level, and high hemoglobin level can be considered independent predictors of this phenomenon. PMID- 26889460 TI - Comparison of the Effects of Coronary Artery Bypass Grafting Versus Medical Therapy on Short and Long Term Outcomes in Octogenarian Patients With Multi Vessel Coronary Artery Disease. AB - BACKGROUND: Appropriate treatment methods lead to a reduced rate of mortality and morbidity, and an improved quality of life, in patients with multi-vessel coronary artery disease. OBJECTIVES: In this study, we compared short and long term outcomes of coronary artery bypass grafting (CABG) versus medical therapy in patients 80 years of age and older with multi-vessel coronary artery disease (MVCAD). PATIENTS AND METHODS: In this retrospective study, 50 octogenarian patients with MVCAD who underwent CABG were compared with 50 patients in the same condition who were treated with medical therapy during the same time. The primary objective was to compare mortality and morbidity rates, as well as other factors such as the occurrence of chest pain, deterioration of the NYHA functional class, and re-hospitalization, between the two groups. The comparison was made using medical records from the five years post-treatment. RESULTS: After five years, the overall mortality rate included 11 patients (22%) in the CABG group versus 18 patients (36%) in the medical therapy group; this difference was not significant between the two groups (P = 0.186). Regarding short-term outcomes, in the CABG group, cardiogenic shock occurred in 9 patients (18%), renal failure in 13 patients (26%), pulmonary complications in 9 patients (18%) and neurologic complications in 3 patients (6%); in the medical therapy group, these same complications occurred, respectively, in 6 patients (12%), 7 patients (14%), 10 patients (20%) and 1 patient (2%). In addition to these factors, freedom from chest pain and improvement in the functional class among the CABG group was significantly higher than among the medical therapy group (P = <0.001). CONCLUSIONS: CABG may be the superior form of treatment for long-term outcomes in terms of the relief of chest pain, improvement of the functional class, reduced need for re-admission, and later death for octogenarians. However, short-term morbidity may be higher among the CABG group, but the mortality rate after 30 days is quite similar. PMID- 26889459 TI - The Prevalence of Overweight and Obesity in Children Under 5 Years in Tehran, Iran, in 2012: A Population-Based Study. AB - BACKGROUND: Overweight and obesity in children are a serious problem. They are increasingly prevalent and associated with a wide range of health problems in adulthood. Monitoring their status is essential for effective planning in the health system. OBJECTIVES: This study aimed to assess the prevalence of overweight and obesity in children below 5 years in Tehran in 2012. PATIENTS AND METHODS: This cross-sectional study employed data provided by the urban health equity assessment in Tehran. The sample comprised a total of 4656 children under 5 years, recruited via multistage sampling. Data were collected through questionnaires and anthropometric measures of height and weight. The WHO child growth standards were used to determine overweight and obesity. Data were analyzed using chi-square tests, with SPSS version 11.5. RESULTS: The prevalence of overweight and obesity in children were 12% and 23.7% respectively. The prevalence of overweight was significantly higher in girls than boys and the prevalence of obesity was significantly higher in boys than girls (P = 0.001). Obesity was more prevalent in children from high economic percentiles, but this finding was not statistically significant. CONCLUSIONS: The prevalence of overweight and obesity in children under 5 years is high. Overweight and obesity should be considered an epidemic and serious health problem in Tehran. They certainly require more attention and intervention. PMID- 26889462 TI - Percutaneous Retrieval of an Embolized Catheter Tip With the Balloon Dilatation Technique. AB - INTRODUCTION: Increasing numbers of complex percutaneous coronary interventions have been accompanied by various intra-procedural complications. The fracture and embolization of devices or their fragments are potentially life-threatening situations, depending on the site of embolization. Different non-surgical methods to handle embolic complications have been proposed for different clinical situations. CASE PRESENTATION: We present a case of a distally embolized catheter fragment that was percutaneously retrieved. The catheter fragment was tightly held by the inflated balloon, moved together with the system, and successfully retrieved out of the circulation via the femoral sheath. Considerable distal embolization of the foreign body and retrieval with the balloon dilatation technique are the unique features of this case. CONCLUSIONS: The present case appears to offer a safe and relatively simple method of balloon dilatation inside the lumen of the embolized fragment when the foreign body is too distal to retrieve with conventional snare systems. PMID- 26889461 TI - Do Cardiometabolic Risk Factors Relative Risks Differ for the Occurrence of Ischemic Heart Disease and Stroke? AB - BACKGROUND: The effects of the risk factors of ischemic heart disease (IHD) and stroke on the occurrence of these diseases differ between different populations. OBJECTIVES: To study the difference in the effects of different cardiovascular (CVD) risk factors on the incidence of IHD and stroke in an Iranian adult population. PATIENTS AND METHODS: The Isfahan Cohort Study (ICS) is a longitudinal study that followed up 6323 subjects older than 35 years with no history of CVD since 2001. Of the original sample, only 5431 participants were contacted and followed up until 2011. The end points were the occurrence of IHD (defined as fatal and non-fatal myocardial infarction, unstable angina, and sudden cardiac death) and stroke. After 10 years of follow-up, 564 new cases of IHD and 141 new cases of stroke were detected. The relative risks (RRs) of cardiometabolic risk factors such as hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, high low-density lipoprotein cholesterol (LDL-C) level, low high-density lipoprotein cholesterol (HDL-C) level, current smoking, obesity, high waist-to-hip ratio, family history of CVD, and metabolic syndrome were compared between IHD and stroke patients. The ratio of relative risks (RRR) was calculated for comparing two RRs and estimated adjusted RRR was calculated by using generalized linear regression with a log link and binomial distribution. RESULTS: The RRs of the occurrence of IHD and stroke in diabetic patients were 1.94 and 3.26, respectively, and the difference was statistically different (P = 0.016). The RR of high LDL-C was significantly higher for IHD than for stroke (P = 0.045), while all the other risk factors showed similar RRs for IHD and stroke, with no significant difference in their RRR, including hypertension. Diabetes and hypertension had the highest RRs for IHD, followed by diabetes, metabolic syndrome, and hypertension for stroke. CONCLUSIONS: The effect of diabetes mellitus on stroke was more significant than on IHD, and the effect of high LDL-C level was more significant on IHD than on stroke, other risk factors, including hypertension, have similar RRs for IHD and stroke. Health care professionals need more training regarding the RRs of these risk factors in the Iranian society, and health decision makers should consider it in their future policies. PMID- 26889463 TI - RISK FACTORS FOR SLOW GAIT SPEED: A NESTED CASE-CONTROL SECONDARY ANALYSIS OF THE MEXICAN HEALTH AND AGING STUDY. AB - BACKGROUND: Physical performance tests play a major role in the geriatric assessment. In particular, gait speed has shown to be useful for predicting adverse outcomes. However, risk factors for slow gait speed (slowness) are not clearly described. OBJECTIVES: To determine risk factors associated with slowness in Mexican older adults. DESIGN: A two-step process was adopted for exploring the antecedent risk factors of slow gait speed. First, the cut-off values for gait speed were determined in a representative sample of Mexican older adults. Then, antecedent risk factors of slow gait speed (defined using the identified cut points) were explored in a nested, cohort case-control study. SETTING PARTICIPANTS: One representative sample of a cross-sectional survey for the first step and the Mexican Health and Aging Study (a cohort characterized by a 10-year follow-up). MEASUREMENTS: A 4-meter usual gait speed test was conducted. Lowest gender and height-stratified groups were considered as defining slow gait speed. Sociodemographic characteristics, comorbidities, psychological and health-care related variables were explored to find those associated with the subsequent development of slow gait speed. Unadjusted and adjusted logistic regression models were performed. RESULTS: In the final model, age, diabetes, hypertension, and history of fractures were associated with the development of slow gait speed. CONCLUSIONS: Early identification of subjects at risk of developing slow gait speed may halt the path to disability due to the robust association of this physical performance test with functional decline. PMID- 26889464 TI - The hierarchy of the evidence-based medicine pyramid: classification beyond ranking. PMID- 26889465 TI - Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft. AB - PURPOSE: the efficacy and safety of using a suspensory button for femoral fixation in anatomical anterior cruciate ligament (ACL) reconstruction with bone patellar tendon-bone (BPTB) graft have not been established. The purpose of the current study was to evaluate bone plug integration onto the femoral socket and migration of the bone plug and the EndoButton (EB) (Smith & Nephew, Andover, MA, USA) after rectangular tunnel ACL reconstruction with BPTB autograft. METHODS: thirty-four patients who underwent anatomical rectangular ACL reconstruction with BPTB graft using EB for femoral fixation and in whom three-dimensional (3D) computed tomography (CT) was performed one week and one year after surgery were included in this study. Bone plug integration onto the femoral socket, bone plug migration, soft tissue interposition, EB migration and EB rotation were evaluated on 3D CT. The clinical outcome was also assessed and correlated with the imaging outcomes. RESULTS: the bone plug was integrated onto the femoral socket in all cases. The incidence of bone plug migration, soft tissue interposition, EB migration and EB rotation was 15, 15, 9 and 56%, respectively. No significant association was observed between the imaging outcomes. The postoperative mean Lysholm score was 97.1 +/- 5.0 points. The postoperative side-to-side difference, evaluated using a KT-2000 arthrometer, averaged 0.5 +/- 1.3 mm. There were no complications associated with EB use. Imaging outcomes did not affect the postoperative KT side-to-side difference. CONCLUSIONS: the EB is considered a reliable device for femoral fixation in anatomical rectangular tunnel ACL reconstruction with BPTB autograft. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26889466 TI - Repair versus shaving of partial-thickness articular-sided tears of the upper subscapularis tendon. A prospective randomized controlled trial. AB - PURPOSE: the purpose of this study was to evaluate whether treating partial thickness articular-sided tears of the upper subscapularis (SSC) tendon with a dedicated suture anchor would result in an internal rotation strength improvement compared with simple shaving of the SSC tendon and footprint. METHODS: twenty-six patients with a limited SSC tendon tear (equal or inferior to the most superior centimeter) in association with a posterosuperior cuff lesion were prospectively randomized to two treatments: repair with a dedicated suture anchor versus shaving of the tendon and footprint. The patients also underwent long head of the biceps (LHB) treatment and posterosuperior cuff tear repair. In each patient the following parameters were measured both preoperatively and at a minimum follow-up of 2.5 years: strength in internal rotation in the bear-hug testing position (using a digital tensiometer), DASH score and Constant scores. MRI assessment of tendon healing was performed at the final follow-up. RESULTS: twenty of the 26 patients (76%) were reviewed after a mean follow-up time of 42 months: 11 patients had undergone SSC tendon repair and nine simple shaving. At final follow up no significant differences were found between the repaired and shaving group in strength in internal rotation (9.5 +/- 3.8 kg versus 10.3+/-5.4 kg; p=0.7). The DASH score and Constant score also failed to show significant differences between the two groups. Furthermore, no significant difference in SSC tendon healing rate was observed on MRI evaluation. CONCLUSIONS: partial-thickness articular-sided tear of the upper SSC tendon in association with a posterosuperior rotator cuff repair and LHB treatment, when limited to the superior centimeter of the SSC tendon, shows a comparable performance in terms of strength in internal rotation either after simple shaving or a tendon-to-bone repair. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID- 26889467 TI - Intra-articular glenohumeral injections of HYADD(r)4-G for the treatment of painful shoulder osteoarthritis: a prospective multicenter, open-label trial. AB - PURPOSE: numerous experimental and clinical studies in osteoarthritis (OA) have demonstrated that intra-articular (IA) administration of hyaluronic acid can improve the altered rheological properties of the synovial fluid and exert protective and reparative effects on the joint structure. The objective of this study was to evaluate the safety and performance of HYADD(r)4-G (Hymovis(r)) in patients with glenohumeral joint OA. METHODS: forty-one patients with shoulder pain and limited shoulder function resulting from concentric glenohumeral joint OA were enrolled in a multicenter clinical trial. Patients received two HYADD(r)4 G injections administered one week apart. The main outcome measure was improvement in shoulder pain on movement at six months as assessed through a 100 mm visual analog scale (VAS), range of motion (ROM) values, and Constant-Murley Shoulder Outcome Score (CS). RESULTS: two IA injections of HYADD(r)4-G (Hymovis(r)) significantly decreased pain and improved shoulder function for up to six months from the first injection. The VAS score decreased (from 66.1 mm to 37.7 mm at six months) and improvements were recorded in the total CS and in the ROM values ( rotation decreased from a mean value of 54.2 degrees at baseline to 63.2 degrees at six months and internal rotation from a mean value of 44.0 degrees at baseline to 45.7 degrees at 26 weeks). No serious adverse events occurred. CONCLUSIONS: the study results demonstrated that two IA injections of HYADD(r)4-G (Hymovis(r)) may be a safe and effective treatment option for shoulder pain associated with glenohumeral OA and that the effects of the injections are still present for up to six months after the treatment. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26889468 TI - Early joint degeneration and antagonism between growth factors and reactive oxygen species. Is non-surgical management possible? AB - PURPOSE: in pathological conditions such as osteo-arthritis (OA), overproduction of reactive oxygen species (ROS) may overwhelm the antioxidant defenses of chondrocytes, thus promoting oxidative stress and cell death. It can be hypothesized that increasing the antioxidant machinery of chondrocytes may prevent the age-associated progression of this disease. Growth factors (GFs) play an important role in promoting both the resolution of inflammatory processes and tissue repair. In view of these considerations, we set out to investigate the protective effect, against H2O2-induced oxidative cell death, potentially exerted by fluid drained from the joint postoperatively. METHODS: the present study was conducted in 20 patients diagnosed with bilateral knee osteoarthritis and treated, between January 2013 and June 2014, with prosthetic knee implantation on the side more affected by the arthritic process, together with intraoperative placement of a closed-circuit drainage aspiration system. As a result, 20 different serum samples were collected from the drained articular fluid, prepared using two different methodologies. In addition, forty blood serum samples were obtained and prepared: 20 from the surgically treated patients and 20 from healthy controls. The present work was undertaken to investigate the potential protective effect of sera obtained from articular fluid drainage against hydrogen peroxide-induced oxidative stress in cultured human chondrocytes. RESULTS: exposure of chondrocytes to hydrogen peroxide elicited a dose-dependent increase in oxidative stress and chondrocyte cell death, phenomena that were significantly counteracted by the pre-treatment of cell cultures with sera from articular fluid drainage. CONCLUSIONS: oxidatively stressed chondrocytes treated with sera obtained from articular fluid drainage lived longer than those treated with blood serum samples and longer than untreated ones. CLINICAL RELEVANCE: synovial fluids are usually discarded once the drainage reservoir is full; instead they could benefit the patients from whom they are collected, as they are rich in growth factors and they may act as antagonists of ROS effects. Accordingly, they could be used to treat chondropathies, early OA, and mild OA located in other sites. PMID- 26889469 TI - Use of the KineSpring system in the treatment of medial knee osteoarthritis: preliminary results. AB - PURPOSE: the purpose of this study was to analyze our preliminary results obtained with the KineSpring system in patients suffering from medial compartment knee osteoarthritis (OA). METHODS: between September 2012 and May 2014, 53 patients underwent treatment with the KineSpring system. Patient self-assessment was performed pre-operatively and at 3, 6 and 12 months postoperatively, and included the KOOS, Tegner activity score, Lysholm functional knee score, VAS knee pain score, and IKDC score. Device- and procedure-related adverse events were recorded. RESULTS: mean KOOS subscales, except for the Sport/Recreation subscale at six months, improved over time. Mean WOMAC Pain and Function domains, Lysholm score, IKDC score and VAS knee pain score improved over the follow-up period and were significantly improved at 3, 6 and 12 months postoperatively compared to baseline. Mean Tegner score improved slightly over time. In 5 of the 53 (9.4%) patients re-operation was necessary. In 3 patients the device was removed due to infection (one case) or persistent knee pain (two cases). Surgical arthrolysis was performed in two patients. CONCLUSIONS: in our preliminary experience, the KineSpring system gave good short-term clinical results. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 26889470 TI - A new hydrogel for the conservative treatment of meniscal lesions: a randomized controlled study. AB - PURPOSE: this study aimed to investigate the efficacy of intra-articular (IA) administration of a hydrogel formulation obtained from a hyaluronic acid (HA) derivative (HYADD4((r))) in the management of meniscal tears and in meniscal tear repair. METHODS: fifty subjects with degenerative meniscal tears were enrolled into this single-site, observer-blind, parallel-group study. Clinical evaluations were performed at baseline and after 14, 30 and 60 days. Clinical outcomes included: pain reduction (Visual Analog Scale), improvement of knee functionality (WOMAC questionnaire), reduction in length and depth of the meniscal lesion (MRI confirmed) and SF-36 questionnaire scores. Local tolerability and safety were also investigated. RESULTS: a significant reduction in VAS pain (p< 0.001) in favor of HYADD4((r)) was recorded at day 14 and maintained at all the follow-up assessments. Data on knee functionality were in line with the VAS pain assessment results. A significant reduction in length and depth of the meniscal lesion, assessed using MRI, was found in the HYADD4((r)) group compared to the control group (p<0.001). CONCLUSIONS: the results of this study may indicate a new treatment option in the conservative management of patients complaining of pain due to meniscal tears. The MRI data suggest that the hydrogel formulation of HA used in this study may also play a role in the healing process of the lesion. LEVEL OF EVIDENCE: Level I, prospective randomized clinical trial. PMID- 26889471 TI - The management of chronic osteoarticular pain in the outpatient setting: results of an ASON audit. AB - The management of patients with chronic osteoarticular pain requires a comprehensive clinical evaluation and a multidisciplinary approach. Thirty specialists (orthopedic specialists, rheumatologists, physiatrists), members of the National Association of Osteoarticular Specialists (ASON), attended a specific training course in the use of a standardized medical record designed for the management of osteoarticular pain in outpatients. An audit on 888 medical records was later conducted and it showed that use of this instrument led to an improvement in the diagnostic-therapeutic approach. A complete and accurate medical record compilation process may also promote collaborative interaction among the healthcare practitioners involved and this can result in greater efficiency and continuity of care. ASON recommends expediting the use of electronic tools to facilitate information-sharing among pain care specialists. This study shows that the use of electronic tools facilitates the exchange of information between healthcare providers. ASON supports the adoption of similar instruments in order to improve the management of chronic pain. LEVEL OF EVIDENCE: Level III, cross-sectional survey. PMID- 26889473 TI - Postoperative pectoral swelling after shoulder arthroscopy. AB - Fluid extravasation is possibly the most common complication of shoulder arthroscopy. Shoulder arthroscopy can lead to major increases in the compartment pressure of adjacent muscles and this phenomenon is significant when an infusion pump is used. This article describes a case of pectoral swelling due to fluid extravasation after shoulder arthroscopy. A 24-year-old male underwent an arthroscopic Bankart repair for recurrent shoulder dislocation. The surgery was performed in the beach chair position and lasted two hours. At the end of the procedure, the patient was found to have left pectoral swelling. A chest radiography showed no abnormality. Pectoral swelling due to fluid extravasation after shoulder arthroscopy has not previously been documented. PMID- 26889472 TI - Results of meniscectomy and meniscal repair in anterior cruciate ligament reconstruction. AB - Meniscal tears are commonly associated with anterior cruciate ligament (ACL) injuries. A deficient medial meniscus results in knee instability and could lead to higher stress forces on the ACL reconstruction. Comparison of results in meniscectomy and meniscal repairs revealed worse clinical outcomes in meniscectomy, but higher re-operation rates in meniscal repairs. Our aim was to review the results of ACL reconstruction associated with meniscectomy or meniscal repair. PMID- 26889474 TI - Successful Treatment of Dual-Positive Anti-Myeloperoxidase and Anti-Glomerular Basement Membrane Antibody Vasculitis with Pulmonary-Renal Syndrome. AB - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and anti glomerular basement membrane (GBM) disease are two separate diseases, while sometimes they can coexist together. The exact mechanisms are not clear, but due to the rapid progression and poor prognosis, prompt and aggressive treatment is usually required. We treated with steroids combined with cyclophosphamide and rituximab an 84-year-old man with ANCA-associated vasculitis and anti-GBM disease who had prior pulmonary fibrosis and a coexisting anterosuperior mediastinal mass. Conventional therapy including steroids, plasmapheresis and cyclophosphamide failed to attenuate the anti-GBM disease, yet he responded to an alternative treatment of rituximab. This case suggests the efficacy of steroids and immunosuppressant for the treatment of a dual-positive case with an anterosuperior mediastinal mass. PMID- 26889475 TI - Benefits of the Nephros Dual Stage Ultrafilter in Chronic Hemodialysis Patients: Evidence for Improved ESA Responsiveness. AB - Installation of the Nephros Dual Stage Ultrafilter (DSU) added to a conventional hemodialysis unit to achieve ultrapure dialysate was tested in a group of 23 stable outpatients on chronic hemodialysis. Comparing the 6-month period prior to the installation of the filters (as baseline) to the 6-month period after the installation of the filters, we found a significant 40% reduction in the darbepoetin dose needed to maintain a stable hemoglobin level (p < 0.001). In addition, surrogate inflammatory markers, WBC count and serum albumin level, showed small but statistically significant improvements (p = 0.008 and p = 0.042, respectively). In conclusion, the use of the Nephros DSU to further reduce endotoxin exposure in chronic hemodialysis patients can result in improved erythropoiesis-stimulating agent (ESA) responsiveness and a lower ESA dose. PMID- 26889476 TI - Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child. AB - Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID- 26889477 TI - Towards precision medicine in epilepsy surgery. AB - Up to a third of all patients with epilepsy are refractory to medical therapy even in the context of the introduction of new antiepileptic drugs (AEDs) with considerable advantages in safety and tolerability over the last two decades. It has been widely accepted that epilepsy surgery is a highly effective therapeutic option in a selected subset of patients with refractory focal seizure. There is no doubt that accurate localization of the epileptogenic zone (EZ) is crucial to the success of resection surgery for intractable epilepsy. The pre-surgical evaluation requires a multimodality approach wherein each modality provides unique and complimentary information. Accurate localization of EZ still remains challenging, especially in patients with normal features on MRI. Whereas substantial progress has been made in the methods of pre-surgical assessment in recent years, which widened the applicability of surgical treatment for children and adults with refractory seizure. Advances in neuroimaging including voxel based morphometric MRI analysis, multimodality techniques and computer-aided subtraction ictal SPECT co-registered to MRI have improved our ability to identify subtle structural and metabolic lesions causing focal seizure. Considerable observations from animal model with epilepsy and pre-surgical patients have consistently found a strong correlation between high frequency oscillations (HFOs) and epileptogenic brain tissue that suggest HFOs could be a potential biomarker of EZ. Since SEEG emphasizes the importance to study the spatiotemporal dynamics of seizure discharges, accounting for the dynamic, multidirectional spatiotemporal organization of the ictal discharges, it has greatly deep our understanding of the anatomo-electro-clinical profile of seizure. In this review, we focus on some state-of-the-art pre-surgical investigations that contribute to the precision medicine. Furthermore, advances also provide opportunity to achieve the minimal side effects and maximal benefit individually, which meets the need for the current concept of precision medicine in epilepsy surgery. PMID- 26889478 TI - Precision medicine in spinocerebellar ataxias: treatment based on common mechanisms of disease. AB - Spinocerebellar ataxias (SCAs) are a heterogeneous group of dominantly inherited neurodegenerative disorders affecting the cerebellum and its associated pathways. There are no available symptomatic or disease-modifying therapies available for any of the over 30 known causes of SCA. In order to develop precise treatments for SCAs, two strategies can be employed: (I) the use of gene-targeting strategies to silence disease-causing mutant protein expression; and (II) the identification and targeting of convergent mechanisms of disease across SCAs as a basis for treatment. Gene targeting strategies include RNA interference and antisense oligonucleotides designed to silence mutant genes in order to prevent mutant protein expression. These therapies can be precise, but delivery is difficult and many disease-causing mutations remain unknown. Emerging evidence suggests that several common disease mechanisms may exist across SCAs. Disrupted protein homeostasis, RNA toxicity, abnormal synaptic signaling, altered intracellular calcium handling, and altered Purkinje neuron membrane excitability are all disease mechanisms which are seen in multiple etiologies of SCA and could potentially be targeted for treatment. Clinical trials with drugs such as riluzole, a potassium channel activator, show promise for multiple SCAs and suggest that convergent disease mechanisms do exist and can be targeted. Precise treatment of SCAs may be best achieved through pharmacologic agents targeting specific disrupted pathways. PMID- 26889479 TI - Toward precision medicine in Parkinson's disease. AB - Precision medicine refers to an innovative approach selected for disease prevention and health promotion according to the individual characteristics of each patient. The goal of precision medicine is to formulate prevention and treatment strategies based on each individual with novel physiological and pathological insights into a certain disease. A multidimensional data-driven approach is about to upgrade "precision medicine" to a higher level of greater individualization in healthcare, a shift towards the treatment of individual patients rather than treating a certain disease including Parkinson's disease (PD). As one of the most common neurodegenerative diseases, PD is a lifelong chronic disease with clinical and pathophysiologic complexity, currently it is treatable but neither preventable nor curable. At its advanced stage, PD is associated with devastating chronic complications including both motor dysfunction and non-motor symptoms which impose an immense burden on the life quality of patients. Advances in computational approaches provide opportunity to establish the patient's personalized disease data at the multidimensional levels, which finally meeting the need for the current concept of precision medicine via achieving the minimal side effects and maximal benefits individually. Hence, in this review, we focus on highlighting the perspectives of precision medicine in PD based on multi-dimensional information about OMICS, molecular imaging, deep brain stimulation (DBS) and wearable sensors. Precision medicine in PD is expected to integrate the best evidence-based knowledge to individualize optimal management in future health care for those with PD. PMID- 26889482 TI - The incidence and mortality of esophageal cancer and their relationship to development in Asia. AB - BACKGROUND: Esophageal cancer is the most common cancer in less developed countries. It is necessary to understand epidemiology of the cancer for planning. The aim of this study was to evaluate the incidence and mortality of esophageal cancer, and its relationship with Human Development Index (HDI) and its components in Asia in 2012. METHODS: This study was an Ecological study, which conducted based on GLOBOCAN project of WHO for Asian counters. We assess the correlation between standardized incidence rates (SIR) and standardized mortality rates (SMR) of esophageal cancer with HDI and its components with using of SPSS18. RESULTS: A total of 337,698 incidence (70.33% were males and 29.87% females. Sex ratio was 2.37) and 296,734 death (69.45% in men and 30.54% in women. The sex ratio was 2.27) esophageal cancer was recorded in Asian countries in 2012. Five countries with the highest SIR and SMR of esophageal cancer were Turkmenistan, Mongolia and Tajikistan, Bangladesh and China respectively. Correlation between HDI and SIR was -0.211 (P=0.159), in men -0.175 (P=0.244) and in women -0.231 (P=0.123). Also between HDI and SMR -0.250 (P=0.094) in men 0.226 (P=0.131) and in women -0.251 (P=0.037). CONCLUSIONS: The incidence of esophageal cancer is more in less developed and developing countries. Statistically significant correlation was not found between standardized incidence and mortality rates of esophageal cancer, and HDI and its dimensions, except for life expectancy at birth. PMID- 26889483 TI - Multiple imputation with multivariate imputation by chained equation (MICE) package. AB - Multiple imputation (MI) is an advanced technique for handing missing values. It is superior to single imputation in that it takes into account uncertainty in missing value imputation. However, MI is underutilized in medical literature due to lack of familiarity and computational challenges. The article provides a step by-step approach to perform MI by using R multivariate imputation by chained equation (MICE) package. The procedure firstly imputed m sets of complete dataset by calling mice() function. Then statistical analysis such as univariate analysis and regression model can be performed within each dataset by calling with() function. This function sets the environment for statistical analysis. Lastly, the results obtained from each analysis are combined by using pool() function. PMID- 26889480 TI - Toward precision medicine in amyotrophic lateral sclerosis. AB - Precision medicine is an innovative approach that uses emerging biomedical technologies to deliver optimally targeted and timed interventions, customized to the molecular drivers of an individual's disease. This approach is only just beginning to be considered for treating amyotrophic lateral sclerosis (ALS). The clinical and biological complexities of ALS have hindered development of effective therapeutic strategies. In this review we consider applying the key elements of precision medicine to ALS: phenotypic classification, comprehensive risk assessment, presymptomatic period detection, potential molecular pathways, disease model development, biomarker discovery and molecularly tailored interventions. Together, these would embody a precision medicine approach, which may provide strategies for optimal targeting and timing of efforts to prevent, stop or slow progression of ALS. PMID- 26889481 TI - Merging technology and clinical research for optimized post-surgical rehabilitation of lung cancer patients. AB - BACKGROUND: The 21(st) century has ushered in an age of wireless communication and technological breakthroughs providing researchers with opportunities and challenges as they incorporate this technology into their research. This paper presents the challenges our team encountered introducing new technologies and how they were overcome for an intervention for post-thoracotomy non-small cell lung cancer (NSCLC) patients. METHODS: Our intervention incorporated the Nintendo Wii Fit Plus virtual-reality walking and balance exercise into a home-based rehabilitation program. The intervention is novel and innovative in that the intervention provides light-intensity exercise post-thoracotomy for NSCLC patients immediately after return to home from the hospital. The intervention overcomes the barriers of conventional exercise programs that require travel, conventional exercise equipment, and begin months after surgery. RESULTS: When translating new technology to research, researchers need to consider a number of factors that need to be addressed. Institutional Review Boards may need further explanation as to why the technology is safe, potential participants may need to have unfounded concerns explained before enrolling, and the research team needs a plan for introducing the technology to participants with a vast range of skill sets and environments in which they will be using technology. In our study, we addressed each of these factors using varying approaches as we translated how the Wii would be used in a home-based exercise intervention by a highly vulnerable, post-thoracotomy NSCLC population. CONCLUSIONS: While technology brings with it multiple barriers for successful implementation, our team showed that with proper planning and teamwork, researchers can navigate these issues bringing the full benefit of technology to even the most vulnerable of patient populations. PMID- 26889484 TI - Newer therapeutics for hepatitis C. PMID- 26889485 TI - Bladder wall thickness in the assessment of neurogenic bladder: a translational discussion of current clinical applications. AB - The prospective trial by Kim et al. "Can Bladder Wall Thickness Predict Videourodynamic Findings in Children with Spina Bifida?" published in Journal of Urology investigated the measurement of bladder wall thickness (BWT) as a non invasive assessment tool for lower urinary tract changes in neurogenic bladder (NGB). In this study, no significant association was observed between BWT and high-risk urodynamic parameters. This editorial discusses the basic science of bladder wall thickening as well as prior studies relating wall thickness to clinical parameters. Although Kim et al. provide a unique literature contribution in terms of assessment of BWT at defined percent cystometric capacity, specific aspects of study methodology and population may have contributed to a lack of correlation with high-risk urodynamic findings. The application of non-invasive modalities to lower urinary tract assessment of NGB remains a promising and relevant area of future research to prevent progression to end stage lower urinary tract changes for all individuals with spina bifida. PMID- 26889487 TI - Sedative choice and ventilator-associated patient outcomes: don't sleep on delirium. PMID- 26889488 TI - The best sedation drug-a quest for the holy grail? PMID- 26889486 TI - The impact of sedation protocols on outcomes in critical illness. PMID- 26889489 TI - Integrating bevacizumab and radiation treatment of brain metastasis: is there sense and sensibility in this approach? AB - The incidence of brain metastasis has increased over the past decade. Standard treatment options for brain metastases include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgery for patients with operable lesions and either mass effect or need for histologic confirmation of the diagnosis. Patients are living longer due to improvements in systemic therapeutic approaches, included targeted therapies such as inhibition of vascular endothelial growth factor (VEGF) using the monoclonal antibody bevacizumab (Bev). A recent phase I trial (REBECA) investigated adding Bev to whole-brain radiation for patients with brain metastasis from solid tumors. In this Perspectives article, we discuss the results of the REBECA trial in context of advancements in radiation and medical oncology in the era of targeted therapies, and discuss pertinent questions of interest in this field. PMID- 26889490 TI - Venous-to-arterial CO2 differences and the quest for bedside point-of-care monitoring to assess the microcirculation during shock. AB - The microcirculation is the anatomical location of perfusion and substrate exchange, and its functional impairment is of paramount importance during the state of shock. The difference in venous-to-arterial carbon dioxide partial pressures (Pv-aCO2) has recently been reported to correlate with microcirculatory dysfunction during early septic shock with greater fidelity than global hemodynamic parameters. This makes it a potential candidate as a point-of-care test in goal directed therapy that aims to restore microcirculatory function in an emergency clinical context. This early work needs to be explored further, and a better understanding of Pv-aCO2 during the resuscitation and subsequent patient progression is required. The quest for an ideal bedside point-of-care test for microcirculatory behavior is ongoing, and is likely to consist of a combination of non-invasive sublingual microcirculatory monitoring and biochemical tests that reflect tissue perfusion. These tools have the potential to provide more accurate and clinically relevant data with regards to the microcirculation that more conventional resuscitative monitoring such as blood pressure, cardiac output, and serum lactate. PMID- 26889491 TI - The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer. AB - Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID- 26889492 TI - Multiple pulmonary cavitary nodules with pyoderma gangrenosum in patient with rheumatoid arthritis. AB - Pyoderma gangrenosum (PG) is a rare ulcerative neutrophilic disorder of skin. Its pulmonary manifestations are uncommon and only less than forty cases have been reported in the literature previously. PG is associated with variable systemic diseases, most commonly inflammatory bowel disease and hematologic malignancies. It reported rarely in rheumatoid arthritis (RA). We report a case of PG lung involvement in patient with RA associated interstitial lung disease. A 66-year old woman presented with productive cough and recurrent ulcerative lesion on her left ankle. She had a 15-year history of RA associated interstitial lung disease and treated with methotrexate, sulfasalazine, hydroxychloroquine and methylprednisolone. On physical examination, there were a few tender, erythematous subcutaneous nodules ranging from 1 to 3 cm in diameter on her left thigh and left elbow. Anti-neutrophil cytoplasmic antibodies (ANCAs) are negative. Her chest CT scan demonstrated multifocal cavitary consolidations on the background of reticular opacity and honeycombing. Punch biopsy of erythematous nodule on thigh showed neutrophilic abscess with necrotic debris. The skin and lung lesions were rapidly improved with 0.5 mg/kg/day of prednisolone. PMID- 26889493 TI - Peripherally located endobronchial hamartoma mimicking aspergilloma: a case report. AB - We herein report the case of a 75-year-old man with a pulmonary hamartoma that mimicked aspergilloma on chest computed tomography (CT). A CT scan performed to assess an asymptomatic lesion detected on a screening chest radiograph showed a 1.3-cm diameter nodule with an air crescent sign in the left lower lobe. A diagnosis of aspergilloma was made and the patient treated with an antifungal agent for 1 year, following which he underwent radical surgery because of failure of the radiologic lesion to resolve. Pathologic examination of the resected specimen showed an endobronchial hamartoma within the B9 periphery. Peripherally located hamartomas can develop within the peripheral bronchi resulting in an air crescent appearance on radiological images. PMID- 26889494 TI - Reply to Editorial by Mamarelis et al. PMID- 26889495 TI - Erratum: Superficial vessel reconstruction with a Multiview camera system. AB - [This corrects the article DOI: 10.1117/1.JMI.3.1.015001.]. PMID- 26889496 TI - Ocular palatal tremor plus dystonia - new syndromic association. AB - OBJECTIVE: Ocular palatal tremor typically develops after a breach in the Guillian-Mollaret triangle. We herein describe a variant of this syndrome in which dystonia is also present, hence called, here, ocular palatal tremor plus dystonia. METHODS: We assessed eye-head movements and dystonia in six patients with ocular palatal plus dystonia. RESULTS: Among six patients with ocular palatal tremor two had focal dystonia, three had multifocal dystonia, and one had generalized dystonia. The dystonia affected the upper extremities and neck in four patients, the lower extremities in three and the face in two. Three out of four cervical dystonia patients had head tremor. Two patients also had speech involvement. Lack of correlation between eye and head oscillations suggested that head oscillations were not compensatory or secondary to the eye oscillations and vice versa. CONCLUSIONS: We describe a novel variant of ocular palatal tremor with dystonia. We speculate that in such variant the dystonia is possibly could be a result of abnormal cerebellar outflow in patients with a breach in Guillain Mollaret triangle. PMID- 26889498 TI - Interactive Whole-Heart Segmentation in Congenital Heart Disease. AB - We present an interactive algorithm to segment the heart chambers and epicardial surfaces, including the great vessel walls, in pediatric cardiac MRI of congenital heart disease. Accurate whole-heart segmentation is necessary to create patient-specific 3D heart models for surgical planning in the presence of complex heart defects. Anatomical variability due to congenital defects precludes fully automatic atlas-based segmentation. Our interactive segmentation method exploits expert segmentations of a small set of short-axis slice regions to automatically delineate the remaining volume using patch-based segmentation. We also investigate the potential of active learning to automatically solicit user input in areas where segmentation error is likely to be high. Validation is performed on four subjects with double outlet right ventricle, a severe congenital heart defect. We show that strategies asking the user to manually segment regions of interest within short-axis slices yield higher accuracy with less user input than those querying entire short-axis slices. PMID- 26889499 TI - A Latent Source Model for Patch-Based Image Segmentation. AB - Despite the popularity and empirical success of patch-based nearest-neighbor and weighted majority voting approaches to medical image segmentation, there has been no theoretical development on when, why, and how well these nonparametric methods work. We bridge this gap by providing a theoretical performance guarantee for nearest-neighbor and weighted majority voting segmentation under a new probabilistic model for patch-based image segmentation. Our analysis relies on a new local property for how similar nearby patches are, and fuses existing lines of work on modeling natural imagery patches and theory for nonparametric classification. We use the model to derive a new patch-based segmentation algorithm that iterates between inferring local label patches and merging these local segmentations to produce a globally consistent image segmentation. Many existing patch-based algorithms arise as special cases of the new algorithm. PMID- 26889500 TI - Dr Richard Popp speaks of his 'scientific journey' presentation in the prestigious, Meet the Legends lecture at ESC Congress 2015 to Mark Nicholls. PMID- 26889501 TI - Heart failure in the Middle East An Emerging Challenge in a Diverse Environment. PMID- 26889502 TI - Standing is better than sitting while activity is better for the waistline. PMID- 26889503 TI - Removing reimbursement barriers to increase the use of screening, brief intervention, and referral to treatment to prevent risky alcohol use. PMID- 26889497 TI - Virological and immunological characteristics of HIV-infected individuals at the earliest stage of infection. AB - BACKGROUND: The challenges of identifying acute HIV infection (AHI) have resulted in a lack of critical information on early AHI that constrains the development of therapeutics that are designed to eradicate HIV from the infected host. METHODS: AHI participants were recruited from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand into the RV254/SEARCH010 protocol and categorised according to Fiebig stages as follows: Fiebig I (HIV-RNA+, p24 Ag-, HIV IgM-) and Fiebig II-IV (HIV-RNA+, p24 Ag + or -, HIV IgM- or +, Western blot- or indeterminate). Proviral and viral burden and immune activation levels were compared between Fiebig stage groups at the time of AHI. CD4 and CD4/CD8 ratio were also compared between groups before and up to 96 weeks of ART. RESULTS: Median age was 27 years and 96% were male. Fiebig I individuals had lower median HIV-DNA in mononuclear cells from blood (3 vs. 190 copies/106 cells) and gut (0 vs. 898 copies/106 cells), and lower HIV-RNA in blood (4.2 vs. 6.2 log10 copies/mL), gut (1.7 vs. 3.1 log10 copies/mg) and cerebrospinal fluid (2.0 vs. 3.8 log10 copies/mL), when compared to Fiebig II-IV individuals (all P<0.01). Median plasma sCD14 level was lower (1.1 vs. 1.6 MUg/mL) in Fiebig I individuals as was the frequency of CD8+HLADR+CD38+ T cells in blood (7.6 vs. 14.9%, both P<0.05). The median plasma interleukin 6 levels were similar between stages (0.6 in Fiebig I vs. 0.5 pg/mL in Fiebig II-IV, P>0.05). The frequencies of CD4+HLA-DR+CD38+ T cells were also similar between these stages (2.1 vs. 2.6%, P>0.05). Median CD4 count and CD4/CD8 ratio were higher in Fiebig I: 508 vs. 340 cells/mm3 and 1.1 vs. 0.7, respectively (both P<0.001). After ART, CD4 cell count normalised by week 24 in Fiebig I and week 48 in Fiebig II-IV. However, CD4/CD8 ratio was lower in both groups after 96 weeks of ART compared to healthy Thais (P=0.02). CONCLUSIONS: Compared to later AHI stages, Fiebig I was associated with lower HIV burden in blood and tissue compartments, lower immune activation and higher CD4 and CD4/CD8 ratio. ART in Fiebig I-IV resulted in normalisation of CD4 cell count within the first year, supporting the benefit of early ART. However, the CD4/CD8 ratio was not normalised after 2 years of ART in all AHI stages, suggesting some degree of persistent immunological dysfunction even when ART was instituted as early as Fiebig I. PMID- 26889504 TI - Preface. PMID- 26889505 TI - Does the presence of learners affect family medicine obstetric outcomes? AB - OBJECTIVE: To compare patient outcomes and complications before and after involvement of family medicine residents in intrapartum care. DESIGN: Secondary data analysis. SETTING: London, Ont. PARTICIPANTS: Obstetric patients of a family physician with a special interest in obstetrics. MAIN OUTCOME MEASURES: Total number of births attended and births missed, as well as rates of inductions, augmentations for dystocia, augmentations for prelabour ruptured membranes, types of births (ie, normal vaginal, vacuum-assisted, low and outlet forceps deliveries; cesarean sections; and obstetrician-assisted vaginal births), and perineal outcomes (ie, intact; first-, second-, third-, or fourth-degree tears; episiotomies; and episiotomies with third-or fourth-degree extensions). RESULTS: During the period of time when family medicine residents were involved in intrapartum care, women sustained slightly more second-degree tears, and more cesarean sections were performed. Fewer women had vacuum-assisted births or unmedicated births. There were no significant differences in rates of normal vaginal births, low and outlet forceps deliveries, and perineal trauma (other than second-degree tears) including episiotomies. CONCLUSION: Women experienced slightly more second-degree tears when residents were involved in their deliveries. The increased number of second-degree tears might be because of residents' limited experience in providing intrapartum care. More important, there was no increase in other serious perineal trauma or episiotomy when residents provided supervised intrapartum care. This should reassure women and family practice obstetricians who choose to receive and provide obstetric care in a family practice teaching unit. The increase in rates of epidural use and cesarean sections and the decrease in rates of vacuum-assisted births reflect obstetric trends in Canada over the past decade. PMID- 26889506 TI - Reasons for delays in diagnosis of anal cancer and the effect on patient satisfaction. AB - OBJECTIVE: To quantify the time to diagnosis of anal cancer after onset of symptoms, to identify reasons for delays in diagnosis, and to identify the effect of delays on patient satisfaction. DESIGN: Retrospective questionnaire. SETTING: Cross Cancer Institute in Edmonton, Alta. PARTICIPANTS: Patients newly diagnosed with anal cancer on their first visit to the centre. MAIN OUTCOME MEASURES: Timeline from first symptoms to first access to medical care and to diagnosis, and patient satisfaction. RESULTS: Twenty-six patients completed the survey. Although most sought medical attention promptly, 19% waited for more than 6 months. At first visits after symptom onset, a rectal examination was performed in only 54% of patients, a diagnosis of hemorrhoids was given in 27% of patients, and further investigations were ordered in only 54% of patients. If a misdiagnosis of hemorrhoids was made, substantially more visits were required to diagnose the cancer. An average of 3.2 months after the first visit to a physician and 7.4 months after onset of symptoms was needed to obtain a diagnosis. Overall, 28% of patients believed there were no diagnostic delays and 40% of patients thought they were responsible for the delay. Overall, 72% of patients were satisfied with the care they received. Patients who were dissatisfied perceived the delay in diagnosis to be because no action was taken by a physician or the wait was too long for tests or referrals. CONCLUSION: To reduce delays in diagnosis, it might be important to educate relevant populations about symptoms of anal cancer. In addition, primary care physicians must maintain a high index of suspicion of anal cancer in high-risk populations. Finally, there must be a system-wide increase in access to further investigations through gastroenterologists and general surgeons. PMID- 26889507 TI - Physician Enabling Skills Questionnaire: Validation of a newly developed instrument in primary health care. AB - OBJECTIVE: To evaluate the reliability and validity of the newly developed Physician Enabling Skills Questionnaire (PESQ) by assessing its internal consistency, test-retest reliability, concurrent validity with patient-centred care, and predictive validity with patient activation and patient enablement. DESIGN: Validation study. SETTING: Saguenay, Que. PARTICIPANTS: One hundred patients with at least 1 chronic disease who presented in a waiting room of a regional health centre family medicine unit. MAIN OUTCOME MEASURES: Family physicians' enabling skills, measured with the PESQ at 2 points in time (ie, while in the waiting room at the family medicine unit and 2 weeks later through a mail survey); patient-centred care, assessed with the Patient Perception of Patient-Centredness instrument; patient activation, assessed with the Patient Activation Measure; and patient enablement, assessed with the Patient Enablement Instrument. RESULTS: The internal consistency of the 6 subscales of the PESQ was adequate (Cronbach alpha = .69 to .92). The test-retest reliability was very good (r = 0.90; 95% CI 0.84 to 0.93). Concurrent validity with the Patient Perception of Patient-Centredness instrument was good (r = -0.67; 95% CI -0.78 to -0.53; P < .001). The PESQ accounts for 11% of the total variance with the Patient Activation Measure (r2 = 0.11; P = .002) and 19% of the variance with the Patient Enablement Instrument (r2 = 0.19; P < .001). CONCLUSION: The newly developed PESQ presents good psychometric properties, allowing for its use in practice and research. PMID- 26889508 TI - Family medicine residents' practice intentions: Theory of planned behaviour evaluation. AB - OBJECTIVE: To assess residents' practice intentions since the introduction of the College of Family Physicians of Canada's Triple C curriculum, which focuses on graduating family physicians who will provide comprehensive care within traditional and newer models of family practice. DESIGN: A survey based on Ajzen's theory of planned behaviour was administered on 2 occasions. SETTING: McMaster University in Hamilton, Ont. PARTICIPANTS: Residents (n = 135) who were enrolled in the Department of Family Medicine Postgraduate Residency Program at McMaster University in July 2012 and July 2013; 54 of the 60 first-year residents who completed the survey in 2012 completed it again in 2013. MAIN OUTCOME MEASURES: The survey was modeled so as to measure the respondents' intentions to practise with a comprehensive scope; determine the degree to which their attitudes, subjective norms, and perceptions of control about comprehensive practice influence those intentions; and investigate how these relationships change as residents progress through the curriculum. The survey also queried the respondents about their intentions with respect to particular medical services that underpin comprehensive practice. RESULTS: The responses indicate that the factors modeled by the theory of planned behaviour survey account for 60% of the variance in the residents' intentions to adopt a comprehensive scope of practice upon graduation, that there is room for curricular improvement with respect to encouraging residents to practise comprehensive care, and that targeting subjective norms about comprehensive practice might have the greatest influence on improving resident intentions. CONCLUSION: The theory of planned behaviour presents an effective approach to assessing curricular effects on resident practice intentions while also providing meaningful information for guiding further program evaluation efforts in the Department of Family Medicine at McMaster University. PMID- 26889510 TI - Orbital Analysis of Molecular Optical Activity Based on Configuration Rotatory Strength. AB - We present a method to analyze the origin of molecular optical activity in terms of orbital contributions and rotatory strength in configuration space. The method uses quantities already available at completion of standard linear-response calculations of specific rotation and requires minimal manipulation. Preliminary application to (1S,4S)-norborne-none and (P)-2,3-pentadiene shows that only a few orbitals (6 and 4, respectively) contribute significantly to the specific rotation and can be used directly for a qualitative interpretation of this fundamental property. PMID- 26889509 TI - Are primary care providers implementing evidence-based care for breast cancer survivors? AB - OBJECTIVE: To describe the implementation of key best practice guideline recommendations for posttreatment breast cancer survivorship care by primary care providers (PCPs). DESIGN: Descriptive cross-sectional survey. SETTING: Southeastern Ontario. PARTICIPANTS: Eighty-two PCPs: 62 family physicians (FPs) and 20 primary health care nurse practitioners (PHCNPs). MAIN OUTCOME MEASURES: Twenty-one "need-to-know" breast cancer survivorship care guideline recommendations rated by participants as "implemented routinely," "aware of guideline recommendation but not implemented routinely," or "not aware of guideline recommendation." RESULTS: Overall, FPs and PHCNPs in our sample reported similar practice patterns in terms of implementation of breast cancer survivorship guideline recommendations. The PCPs reported routinely implementing approximately half (46.4%, 9.7 of 21) of the key guideline recommendations with breast cancer survivors in their practices. Implementation rates were higher for recommendations related to prevention and surveillance aspects of survivorship care, such as mammography and weight management. Knowledge and practice gaps were highest for recommendations related to screening for and management of long-term effects such as fatigue and distress. There were only a few minor differences reported between FPs and PHCNPs. CONCLUSION: There are knowledge and practice gaps related to implementation of the key guideline recommendations for breast cancer survivorship care in the primary care setting that could be targeted for improvement through educational or other interventions. PMID- 26889511 TI - Exploring the Accuracy Limits of Local Pair Natural Orbital Coupled-Cluster Theory. AB - The domain based local pair natural orbital coupled cluster method with single-, double-, and perturbative triple excitations (DLPNO-CCSD(T)) is an efficient quantum chemical method that allows for coupled cluster calculations on molecules with hundreds of atoms. Because coupled-cluster theory is the method of choice if high-accuracy is needed, DLPNO-CCSD(T) is very promising for large-scale chemical application. However, the various approximations that have to be introduced in order to reach near linear scaling also introduce limited deviations from the canonical results. In the present work, we investigate how far the accuracy of the DLPNO-CCSD(T) method can be pushed for chemical applications. We also address the question at which additional computational cost improvements, relative to the previously established default scheme, come. To answer these questions, a series of benchmark sets covering a broad range of quantum chemical applications including reaction energies, hydrogen bonds, and other noncovalent interactions, conformer energies, and a prototype organometallic problem were selected. An accuracy of 1 kcal/mol or better can readily be obtained for all data sets using the default truncation scheme, which corresponds to the stated goal of the original implementation. Tightening of the three thresholds that control DLPNO leads to mean absolute errors and standard deviations from the canonical results of less than 0.25 kcal/mol (<1 kJ/mol). The price one has then to pay is an increased computational time by a factor close to 3. The applicability of the method is shown to be independent of the nature of the reaction. On the basis of the careful analysis of the results, three different sets of truncation thresholds (termed "LoosePNO", "NormalPNO", and "TightPNO") have been chosen for "black box" use of DLPNO-CCSD(T). This will allow users of the method to optimally balance performance and accuracy. PMID- 26889512 TI - Hydrated Electrons in Water Clusters: Inside or Outside, Cavity or Noncavity? AB - In this work, we compare the applicability of three electron-water molecule pseudopotentials in modeling the physical properties of hydrated electrons. Quantum model calculations illustrate that the recently suggested Larsen-Glover Schwartz (LGS) model and its modified m-LGS version have a too-attractive potential in the vicinity of the oxygen. As a result, LGS models predict a noncavity hydrated electron structure in clusters at room temperature, as seen from mixed one-electron quantum-classical molecular dynamics simulations of water cluster anions, with the electron localizing exclusively in the interior of the clusters. Comparative calculations using the cavity-preferring Turi-Borgis (TB) model predict interior-state and surface-state cluster isomers. The computed associated physical properties are also analyzed and compared to available experimental data. We find that the LGS and m-LGS potentials provide results that appear to be inconsistent with the size dependence of the experimental data. The simulated TB tendencies are qualitatively correct. Furthermore, ab initio calculations on static LGS noncavity structures indicate weak stabilization of the excess electron in regions where the LGS potential preferably and strongly binds the electron. TB calculations give stabilization energies that are in line with the ab initio results. In conclusion, we observe that the cavity-preferring pseudopotential model predicts cluster physical properties in better agreement with experimental data and ab initio calculations than the models predicting noncavity structures for the hydrated electron. PMID- 26889513 TI - Building Markov State Models for Periodically Driven Non-Equilibrium Systems. AB - Non-equilibrium molecular dynamics (NEMD) simulations have seen increased interest the past few years, especially for molecular systems with periodic forcing by external fields (e.g., in the context of studying the effects of electromagnetic radiation on human body tissues). Recently, an NEMD method with local thermostatting has been proposed that allows for the study of non equilibrium processes in a statistically reliable and thermodynamically consistent way. In this article, we demonstrate how to construct Markov state models (MSMs) for such NEMD simulations. MSM building is well-established for systems in equilibrium, where MSMs with only a few (macro-)states allow for accurate reproduction of the essential kinetics of the molecular system under consideration. Non-equilibrium MSMs have not yet been established. This article presents a method for constructing such MSMs and illustrates their validity and usefulness through conformation dynamics of an alanine dipeptide in an external electric field. PMID- 26889514 TI - PREFACE. PMID- 26889515 TI - Parameterization of the DFTB3 method for Br, Ca, Cl, F, I, K, and Na in organic and biological systems. AB - We present an extension to the recent 3OB parametrization of the Density Functional Tight Binding Model DFTB31,2 for biological and organic systems. Parameters for the halogens F, Cl, Br, and I have been developed for use in covalently bound systems and benchmarked on a test set of 106 molecules (the 'OrgX' set), using bonding distances, bonding angles, atomization energies, and vibrational frequencies to assess the performance of the parameters. Additional testing has been done with the X40 set of 40 supramolecular systems containing halogens,3 adding a simple correction for the halogen bonds that are strongly overbound in DFTB3. Furthermore, parameters for Ca, K, and Na as counterions in biological systems have been created. To benchmark geometries as well as ligand binding energies a test set 'BioMe' of 210 molecules has been created that cover coordination to various functional groups frequently occurring in biological systems. The new DFTB3/3OB parameter set outperforms DFT calculations with a double-zeta basis set in terms of energies and can reproduce DFT geometries, with some minor deviations in bond distances and angles due to the use of a minimal basis set. PMID- 26889516 TI - Merging metadynamics into hyperdynamics: accelerated molecular simulations reaching time scales from microseconds to seconds. AB - The hyperdynamics method is a powerful tool to simulate slow processes at the atomic level. However, the construction of an optimal hyperdynamics potential is a task that is far from trivial. Here, we propose a generally applicable implementation of the hyperdynamics algorithm, borrowing two concepts from metadynamics. First, the use of a collective variable (CV) to represent the accelerated dynamics gives the method a very large flexibility and simplicity. Second, a metadynamics procedure can be used to construct a suitable history dependent bias potential on-the-fly, effectively turning the algorithm into a self-learning accelerated molecular dynamics method. This collective variable driven hyperdynamics (CVHD) method has a modular design: both the local system properties on which the bias is based, as well as the characteristics of the biasing method itself, can be chosen to match the needs of the considered system. As a result, system-specific details are abstracted from the biasing algorithm itself, making it extremely versatile and transparent. The method is tested on three model systems: diffusion on the Cu(001) surface and nickel-catalyzed methane decomposition, as examples of "reactive" processes with a bond-length based CV, and the folding of a long polymer-like chain, using a set of dihedral angles as a CV. Boost factors up to 109, corresponding to a time scale of seconds, could be obtained while still accurately reproducing correct dynamics. PMID- 26889517 TI - Estimating error in diffusion coefficients derived from molecular dynamics simulations. AB - The computationally expensive nature of molecular dynamics simulation limits the access to length (nanometer) and time scales (nanosecond) that are orders of magnitude smaller than the experiment it models. This limitation warrants a careful estimation of statistical uncertainty associated with the properties calculated from these simulations. The assumption that a simulation is long enough so that the ergodic hypothesis applies is often invoked in the literature for the computation of properties of interest from a single molecular dynamics simulation. Here, we demonstrate that making this assumption without validation results in poor estimates of the self-diffusion coefficient from a single molecular dynamics simulation of Lennard-Jones fluid. This problem is shown to be even more severe when the diffusion coefficient of macromolecules is calculated from a single molecular dynamics simulation. We have shown that conducting multiple independent simulations is necessary to obtain reliable estimates of diffusion coefficients and their associated statistical uncertainties. We show that even a "routine" calculation of the self-diffusion coefficient for a Lennard Jones fluid, as determined from a linear fit of the mean squared displacement of particles as a function of time, violates the key assumptions of linear regression. A rigorous approach for addressing these issues is presented. PMID- 26889518 TI - Laser-induced demagnetization at ultrashort time scales: predictions of TDDFT. AB - Time-dependent density functional theory (TDDFT) is implemented in an all electron solid-state code for the case of fully unconstrained noncollinear spins. We use this to study intense, short, laser pulse-induced demagnetization in bulk Fe, Co, Ni and find that demagnetization can take place on time scales of <20 fs. It is demonstrated that this form of demagnetization is a two-step process: excitation of a fraction of electrons followed by spin-flip transitions mediated by spin-orbit coupling of the remaining localized electrons. We further show that it is possible to control the moment loss by tunable laser parameters, including frequency, duration, and intensity. PMID- 26889519 TI - A Chemically Meaningful Measure of Electron Localization. AB - Electron localization and delocalization are commonly invoked in the day-to-day rationalization of chemistry. This work addresses the challenges of quantifying this elusive concept in a chemically useful manner. A general principle, requiring the simultaneous quantification of (1) a limited physical volume (classical criterion) and (2) same-spin loneliness (quantum criterion), is introduced. It is demonstrated how, by beginning with the Electron Localization Function (ELF) scalar field, one can choose to discard all points in space where the same-spin loneliness is lower than a certain value. Such a partitioning approach ensures that both criteria for quantifying localization (1 and 2) are simultaneously met. The most chemically instructive results arise when the dividing boundary condition is set by the local behavior of a homogeneous electron gas. The High Electron Localization domain Population (HELP) is introduced and applied for quantifying the localization of individual domains within molecules, as well as a measure of total electron localization in atoms and molecules. Several striking agreements with chemical intuition, experimental measurable quantities, and quantum chemical constructs are demonstrated along with understandable differences. Studies of diatomic molecules agree with current ideas on chemical bonding. The size-dependence and magnitude of localization in linear hydrocarbons is studied and compared to cyclic systems, such as benzene. The proposed methodology offers a straightforward measure for direct and quantitative comparisons between atoms, molecules, and extended condensed matter. PMID- 26889520 TI - Fetal molecular diagnostics from maternal peripheral blood. PMID- 26889563 TI - Modified technique to improve fabrication and outcome of definitive orbital prosthesis. AB - Facial prostheses are generally fabricated from silicones, which provide life like appearance and flexibility. The longevity of silicone, however, is limited because of its tendency to support fungal growth, absorb oils and grease, and edge-tearing susceptibility. Polyurethane (PU) liners have been used on the tissue-bearing surface of such prosthesis to improve tear resistance and fungal resistance. Technique sensitivity, discoloration and metamerism are significant limitations of urethane lining. Further, this liner is incorporated during processing of definitive prosthesis, which precludes try-in of tissue surface of prosthesis. This article describes an alternative lining material for fitting surface of definitive orbital prostheses, which could overcome limitations associated with all silicone or PU lined silicone prostheses. PMID- 26889562 TI - Precise Polymerization of a Highly Tumor Microenvironment-Responsive Nanoplatform for Strongly Enhanced Intracellular Drug Release. AB - The importance of achieving a high content of responsive groups of drug carriers is well-known for achieving rapid intracellular drug release; however, very little research has been published on this subject. Here, we present an entirely new strategy to synthesize a highly reduction-sensitive polymer-drug conjugate with one disulfide bond corresponding to each resultant copolymer through a precise ring-opening polymerization of epsilon-caprolactone that is initiated by a monoprotected cystamine. Simultaneously, the anticancer drug doxorubicin is chemically conjugated to the polymer via pH-responsive hydrazone bonds, which effectively prevent premature drug release in the blood circulation. The 3 aminophenylboronic acid (PBA) targeting ligands endow an active-targeting ability that significantly prompts the specific internalization of nanocarriers by tumor cells and thus results in excellent cytotoxicity against tumor cells. The concept of precise polymerization is put forward to achieve multifunctional nanocarriers for the first time. This study is expected to inspire the development of a highly environment-responsive nanoplatform for drug delivery in future clinical applications. PMID- 26889564 TI - Synergetic Effects of Inorganic Components in Solid Electrolyte Interphase on High Cycle Efficiency of Lithium Ion Batteries. AB - The solid electrolyte interphase (SEI), a passivation layer formed on electrodes, is critical to battery performance and durability. The inorganic components in SEI, including lithium carbonate (Li2CO3) and lithium fluoride (LiF), provide both mechanical and chemical protection, meanwhile control lithium ion transport. Although both Li2CO3 and LiF have relatively low ionic conductivity, we found, surprisingly, that the contact between Li2CO3 and LiF can promote space charge accumulation along their interfaces, which generates a higher ionic carrier concentration and significantly improves lithium ion transport and reduces electron leakage. The synergetic effect of the two inorganic components leads to high current efficiency and long cycle stability. PMID- 26889565 TI - Selective Transformation of Various Nitrogen-Containing Exhaust Gases toward N2 over Zeolite Catalysts. AB - In this review we focus on the catalytic removal of a series of N-containing exhaust gases with various valences, including nitriles (HCN, CH3CN, and C2H3CN), ammonia (NH3), nitrous oxide (N2O), and nitric oxides (NO(x)), which can cause some serious environmental problems, such as acid rain, haze weather, global warming, and even death. The zeolite catalysts with high internal surface areas, uniform pore systems, considerable ion-exchange capabilities, and satisfactory thermal stabilities are herein addressed for the corresponding depollution processes. The sources and toxicities of these pollutants are introduced. The important physicochemical properties of zeolite catalysts, including shape selectivity, surface area, acidity, and redox ability, are described in detail. The catalytic combustion of nitriles and ammonia, the direct catalytic decomposition of N2O, and the selective catalytic reduction and direct catalytic decomposition of NO are systematically discussed, involving the catalytic behaviors as well as mechanism studies based on spectroscopic and kinetic approaches and molecular simulations. Finally, concluding remarks and perspectives are given. In the present work, emphasis is placed on the structure performance relationship with an aim to design an ideal zeolite-based catalyst for the effective elimination of harmful N-containing compounds. PMID- 26889566 TI - Computational Insights into the Rhodium(III)-Catalyzed Coupling of Benzamides and 1,6-Enynes via a Tunable Arylative Cyclization. AB - A density functional theory (DFT) study has been conducted to elucidate the mechanism of the rhodium(III)-catalyzed C-H activation of O-substituted N hydroxybenzamides and cyclohexadienone-containing 1,6-enynes. The impact of different O-substituted internal oxidants (OPiv versus OMe) on the arylative cyclization (i.e., N-Michael addition versus C-Michael addition) has been evaluated in detail. The N-Michael addition pathway proceeded via a Rh(I) species, while Rh(III) remained unchanged throughout the C-Michael addition pathway. The Rh(III)/Rh(I) catalytic cycle in the N-Michael addition pathway was different from those reported previously where the Rh(III)/Rh(V) catalytic cycle was favored for the Rh(III)-catalyzed C-H activation of O-substituted N hydroxybenzamides. The first three steps were similar for the OPiv- and OMe substituted substrates, which involved sequential N-H deprotonation, C-H activation (a concerted metalation-deprotonation process), and 1,6-enyne insertion steps. Starting from a seven-membered rhodacycle, the alternative mechanism would be controlled by the OR substituent. When the substituent was OMe, the unstable seven-membered rhodacycle was readily coordinated by a double bond of the cyclohexadienone which enabled the C-Michael addition reaction. However, the presence of an N-OPiv moiety stabilized the seven-membered rhodacycle through a bidentate coordination which facilitated the N-Michael addition process. PMID- 26889567 TI - Clinical, Refractive and Histological Reversibility of Corneal Additive Surgery in Deep Stroma in an Animal Model. AB - PURPOSE: The aim was to evaluate the reversibility of the clinical and histological changes induced in the corneas of an animal model after removing an intracorneal ring segment (ICRS). METHODS: Surgery for this study was performed in 38 eyes of an experimental animal model (Gallus domesticus) for ICRS surgery (Ferrara technique). The animals without complications were randomized to two groups; in all of them, 1 segment was implanted in each eye and later removed at different times (1 and 3 months after implantation). In each group, after explantation, corneas were processed at different times for histological analysis with hematoxylin and eosin (H&E) stain and electronic microscopy. The refractive state of the eyes was also measured. RESULTS: In corneas without complications (88.23%), explantation was performed correctly. During the first few days, around the area where the ICRS was implanted we observed deposits of cells and a moderate degree of corneal opacity (haze). These signs decreased progressively without disappearing completely. Histologically, at 7 days, we observed hyperplasia and abnormal arrangement of collagen fibers. Later, these findings also decreased in both groups, albeit at a faster rate in group 1. Minimal changes were observed in electron microscopy up to the end of the study in both groups. Preoperative refractive state was achieved at 1 month after explantation in both groups. CONCLUSIONS: ICRS can safely be explanted from the cornea. Refractive reversibility was achieved at 1 month after explantation. However, the clinical and histological findings after ICRS explantation depend on the time from implantation to explantation. PMID- 26889570 TI - Designing a Beryllium-Free Deep-Ultraviolet Nonlinear Optical Material without a Structural Instability Problem. AB - A beryllium-free deep-ultraviolet (deep-UV) nonlinear optical (NLO) material K3Ba3Li2Al4B6O20F is developed mainly by the element substitution of Be for Al and Li from Sr2Be2B2O7 that was considered as one of the most promising deep-UV NLO materials. K3Ba3Li2Al4B6O20F preserves the structural merits of Sr2Be2B2O7 and thus exhibits no layering growth tendency and possesses the optical properties required for deep-UV NLO applications, including deep-UV transparency, phase-matchability, and sufficiently large second-harmonic generation (1.5 * KH2PO4). Furthermore, it overcomes the structural instability problem of Sr2Be2B2O7, which is confirmed by the obtainment of large single crystals and phonon dispersion calculations. These attributes make it very attractive for next generation deep-UV NLO materials. The substitution of Be for Al and Li in beryllium borates provides a new opportunity to design beryllium-free deep-UV NLO materials with good performance. PMID- 26889568 TI - Evaluation of recent New Vaccine Surveillance Network data regarding respiratory syncytial virus hospitalization rates in US preterm infants. AB - In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (<37 wGA) infants evaluated from 2000 to 2005 through the New Vaccine Surveillance Network (NVSN). Here we critically appraise the preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at <32 wGA and 21% to 27% of all preterm infants (<37 wGA). When the NVSN data regarding incidence of RSV hospitalization in preterm infant subgroups were evaluated as a function of chronologic age, preterm infants <32 wGA showed a paradoxical increase in RSV hospitalization with older age, with the highest risk of RSV hospitalization occurring at 18 to 23 months of age. This pattern is most consistent with a reduction in RSV hospitalizations in <32 wGA infants in the first 12 to 18 months of life due to high palivizumab use at these young ages. The NVSN data were not designed to and cannot accurately describe RSV disease burden in preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period. PMID- 26889569 TI - Cross-sectional study of road accidents and related law enforcement efficiency for 10 countries: A gap coherence analysis. AB - OBJECTIVE: Road crashes are considered as the eighth leading causes of death. There is a wide disparity in crash severity and law enforcement efficiency among low-, medium-, and high-income countries. It would be helpful to review the crash severity trends in these countries, identify the vulnerable road users, and understand the law enforcement effectiveness in devising efficient road safety improvement strategies. METHOD: The crash severity, fatality rate among various age groups, and law enforcement strategies of 10 countries representing low income (i.e., India and Morocco), medium-income (i.e. Argentina, South Korea, and Greece), and high-income (i.e., Australia, Canada, France, the UK, and the United States) are studied and compared for a period of 5 years (i.e., 2008 to 2012). The critical parameters affecting road safety are identified and correlated with education, culture, and basic compliance with traffic safety laws. In the process, possible road safety improvement strategies are identified for low income countries. RESULTS: The number of registered vehicles shows an increasing trend for low-income countries as do the crash rate and crash severity. Compliance related to seat belt and helmet laws is high in high-income countries. In addition, recent seat belt- and helmet-related safety programs in middle income countries helped to curb fatalities. Noncompliance with safety laws in low income countries is attributed to education, culture, and inefficient law enforcement. CONCLUSION: Efficient law enforcement and effective safety education taking into account cultural diversity are the key aspects to reduce traffic related injuries and fatalities in low-income countries like India. PMID- 26889571 TI - Reflex Seizures Triggered by Diaper Change in Dravet Syndrome. AB - Dravet syndrome (DS) is a severe epilepsy syndrome characterized by early onset of multiple types of seizures. We report the first case of reflex seizures triggered by diaper change in a girl at 9 months old and 2 years old with a mutation in the SCN1A gene causing DS. Reflex seizures have been reported in patients with DS provoked by increased body temperature or visual stimulation. The case we report widens the spectrum of triggers causing reflex seizures in children with DS. Cortical hyperexcitability resulting from the genetic defect explains the tendency to experience such reflex seizures. PMID- 26889572 TI - Dynamic Electrochemical Measurement of Chloride Ions. AB - This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver chloride electrode is used extensively for potentiometric measurement of chloride ions concentration in electrolyte. In this measurement, long-term and continuous monitoring is limited due to the inherent drift and the requirement of a stable reference electrode. We utilized the chronopotentiometric approach to minimize drift and avoid the use of a conventional reference electrode. A galvanostatic pulse is applied to an Ag/AgCl electrode which initiates a faradic reaction depleting the Cl- ions near the electrode surface. The transition time, which is the time to completely deplete the ions near the electrode surface, is a function of the ion concentration, given by the Nernst equation. The square root of the transition time is in linear relation to the chloride ion concentration. Drift of the response over two weeks is negligible (59 uM/day) when measuring 1 mM [Cl ]using a current pulse of 10 Am(-2). This is a dynamic measurement where the moment of transition time determines the response and thus is independent of the absolute potential. Any metal wire can be used as a pseudo-reference electrode, making this approach feasible for long-term measurement inside concrete structures. PMID- 26889574 TI - Development of CNC prototype for the characterization of the nanoparticle release during physical manipulation of nanocomposites. AB - This work focuses on the release of nanoparticles from commercially used nanocomposites during machining operations. A reliable and repeatable method was developed to assess the intentionally exposure to nanoparticles, in particular during drilling. This article presents the description and validation of results obtained from a new prototype used for the measurement and monitoring of nanoparticles in a controlled environment. This methodology was compared with the methodologies applied in other studies. Also, some preliminary experiments on drilling nanocomposites are included. Size, shape and chemical composition of the released nanoparticles were investigated in order to understand their hazard potential. No significant differences were found in the amount of nanoparticles released between samples with and without nanoadditives. Also, no chemical alteration was observed between the dust generated and the bulk material. Finally, further developments of the prototype are proposed. PMID- 26889575 TI - Monochromatic filter with multiple manipulation approaches by the layered all dielectric patch array. AB - Monochromatic filtering with ultra-narrowband and high spectral contrast is desirable for wide applications in display, image, and other optoelectronics. However, owing to the inherent omhic losses in the metallic materials, a broadband spectrum with a low Q-factor down to 10 inevitably limits the device performance. Herein, we for the first time theoretically propose and demonstrate an ultra-narrowband color-filtering platform based on the layered all-dielectric meta-material (LADM), which consists of a triple-layer high/low/high-index dielectrics cavity structure. Owing to the lossless dielectric materials used, sharp resonances with the bandwidth down to sub-10 nm are observed in the sub wavelength LADM-based filters. A spectral Q-factor of 361.6 is achieved, which is orders of magnitude larger than that of the plasmonic resonators. Moreover, for the other significant factor for evaluation of filtering performance, the spectral contrast reaches 94.5%. These optical properties are the main results of the excitation of the resonant modes in the LADMs. Furthermore, polarization manipulated light filtering is realized in this LADM. The classical Malus law is also confirmed in the reflective spectrum by tuning the polarization state. More interestingly and importantly, the filtering phenomenon shows novel features of the wavelength-independent and tunable resonant intensity for the reflective spectrum when the LADM-based filter is illuminated under an oblique state. High scalability of the sharp reflective spectrum is obtained by tuning the structural parameters. A single-wavelength reflective filtering window is also achieved in the visible frequencies. These features hold promise for the LADM-based filter with wide applications in color engineering, displaying, imaging, etc. PMID- 26889573 TI - Validating the disruption of proliferating cell nuclear antigen interactions in the development of targeted cancer therapeutics. AB - Human DNA replication and repair is a highly coordinated process involving the specifically timed actions of numerous proteins and enzymes. Many of these proteins require interaction with proliferating cell nuclear antigen (PCNA) for activation within the process. The interdomain connector loop (IDCL) of PCNA provides a docking site for many of those proteins, suggesting that this region is critically important in the regulation of cellular function. Previous work in this laboratory has demonstrated that a peptide mimicking a specific region of the IDCL (caPeptide) has the ability to disrupt key protein-protein interactions between PCNA and its binding partners, thereby inhibiting DNA replication within the cells. In this study, we confirm the ability of the caPeptide to disrupt DNA replication function using both intact cell and in vitro DNA replication assays. Further, we were able to demonstrate that treatment with caPeptide results in a decrease of polymerase delta activity that correlates with the observed decrease in DNA replication. We have also successfully developed a surface plasmon resonance (SPR) assay to validate the disruption of the PCNA-pol delta interaction with caPeptide. PMID- 26889576 TI - Understanding How the "Open" of Open Source Software (OSS) Will Improve Global Health Security. AB - Improving global health security will require bold action in all corners of the world, particularly in developing settings, where poverty often contributes to an increase in emerging infectious diseases. In order to mitigate the impact of emerging pandemic threats, enhanced disease surveillance is needed to improve early detection and rapid response to outbreaks. However, the technology to facilitate this surveillance is often unattainable because of high costs, software and hardware maintenance needs, limited technical competence among public health officials, and internet connectivity challenges experienced in the field. One potential solution is to leverage open source software, a concept that is unfortunately often misunderstood. This article describes the principles and characteristics of open source software and how it may be applied to solve global health security challenges. PMID- 26889577 TI - Contextual Factors Among Indiscriminate or Large Attacks on Food or Water Supplies, 1946-2015. AB - This research updates previous inventories of malicious attacks on food and water and includes data from 1946 through mid-2015. A systematic search of news reports, databases, and previous inventories of poisoning events was undertaken. Incidents that threatened or were intended to achieve direct harm to humans and that were either relatively large (more than 4 victims) or indiscriminate in intent or realization were included. Agents could be chemical, biological, or radionuclear. Reports of candidate incidents were subjected to systematic inclusion and exclusion criteria as well as validity analysis (not always clearly undertaken in previous inventories of such attacks). We summarize contextual aspects of the attacks that may be important for scenario prioritization, modelling, and defensive preparedness. Opportunity, and particularly access to dangerous agents, is key to most realized attacks. The most common motives and relative success rate in causing harm were very different between food and water attacks. The likelihood that people were made ill or died also varied by food or water mode and according to motive and opportunity for delivery of the hazardous agent. Deaths and illness associated with attacks during food manufacture and prior to sale have been fewer than those in some other contexts. Valuable opportunities for food defense improvements are identified in other contexts, especially food prepared in private or community settings. PMID- 26889578 TI - Structural Expression of Exo-Anomeric Effect. AB - Structural signatures for exo-anomeric effect have been extracted from the archetypal methyl-beta-D-xyloside using broadband Fourier transform microwave spectroscopy combined with laser ablation. Spectrum analysis allows the determination of a set of rotational constants, which has been unequivocally attributed to conformer cc-beta-(4)C1 g-, corresponding to the global minimum of the potential energy surface, where the aglycon residue (CH3) orientation contributes to maximization of the exo-anomeric effect. Further analysis allowed the determination of the rs structure, based on the detection of 11 isotopologues -derived from the presence of six (13)C and five (18)O atoms--observed in their natural abundances. The observed glycosidic C1-O1 bond length decrease (1.38 A) can be interpreted in terms of the exo-anomeric effect. As such, the exo-anomeric effect presents itself as one of the main driving forces controlling the shape of many biologically important oligosaccharides. PMID- 26889580 TI - Design and Evaluation of the NFL PLAY 60 FITNESSGRAM Partnership Project. AB - This article describes the conceptual design and evaluation strategies used in the NFL PLAY 60 FITNESSGRAM Partnership Project, a large participatory research network focused on building effective school physical education programming. The article summarizes the unique participatory design, recruitment methods, programming strategies, and analytical plans used to evaluate this large project. The study provides unique insight into how to effectively deliver large-scale school-based physical fitness and physical activity programming to support and enhance physical education programming in schools. PMID- 26889579 TI - TNF-alpha Blockade Efficiently Reduced Severe Intestinal Damage in Necrotizing Enterocolitis. AB - OBJECTIVES: To ascertain the beneficial effects of infliximab an inhibitor of tumor necrosis factor alpha (TNF-alpha) on the development of NEC in an experimental NEC rat model. MATERIAL AND METHODS: Thirty newborn Sprague-Dawley rats were randomly divided into three groups as NEC, NEC+ infliximab, and control. NEC was induced by enteral formula feeding, exposure to hypoxia hyperoxia and cold stress. Pups in the NEC+ infliximab group were administered infliximab at a dose of 10 mg/kg daily by intraperitoneal route from the first day until the end of the study. All pups were sacrificed on the 5th day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (TUNEL and caspase-3), and biochemical evaluation, including, total antioxidant status (TAS), total oxidant status (TOS), malonaldehyde (MDA), and myeloperoxdase (MPO) and TNF-alpha activities. RESULTS: We observed better clinical sickness scores, weight gain, and survival rate in the NEC+ infliximab group compared to the NEC group (p < .05). Histopathological and apoptosis examination (TUNEL and immunohistochemical evaluation for caspase-3) revealed lower damage in the NEC+ infliximab group compared to the damage in the NEC group (p < .01). Tissue MDA, MPO, TNF-alpha levels, and TOS were significantly decreased in the NEC+infliximab group, whereas TAS was significantly increased in the NEC + infliximab group (p < .01). CONCLUSION: TNF-alpha blockade with infliximab efficiently reduced the intestinal injury and preserve the intestinal tissues from severe intestinal damage by its complex mechanisms on NEC. Therefore, it may be an alternative option for the treatment of NEC. PMID- 26889581 TI - Implications of Physical Literacy for Research and Practice: A Commentary. AB - Physical literacy is a term that has increasingly gained popularity in recent years. A variety of individuals and organizations have promoted the use of the term internationally, and a variety of claims have been made for the benefits of using the term. A historical overview allows the reader to consider physical literacy as one of many terms that have gained popularity in the field and describes divergent views as well as areas of agreement concerning the term physical literacy. Three North American institutional approaches to physical literacy are discussed. Other issues are also discussed, including assessment and other literacy types (e.g., health, sports). The article is designed to provoke thought among professionals and representatives of institutions concerning physical literacy. PMID- 26889582 TI - Top 10 Research Questions Related to Physical Literacy. AB - The term physical literacy is relatively new, and its definition, conceptual underpinning, how it is measured, how to change it, and its relationship with holistic health and wellness across the life span are a few of many foundational issues that lack consensus. At present, there are more questions than answers. The purpose of this article is to highlight 10 important research questions related to physical literacy with the hope of fueling future research activity and debate. Input was sought from international experts and practitioners on priorities and research gaps related to physical literacy. This list was supplemented by personal experience and research priorities identified in published manuscripts. From these various sources, the top 10 research questions related to physical literacy were compiled. Research related to physical literacy is in its infancy, and many important, even fundamental research questions and priorities remain unanswered. Research needs are summarized within 4 themes: monitoring physical literacy, understanding the physical literacy journey, enhancing physical literacy, and the benefits of physical literacy. Specific research questions relate to identifying measurable aspects of physical literacy and how they change across cultures and throughout the life span, as well as understanding the individual and environmental factors that describe the physical literacy journey and are effective targets for interventions. Physical literacy is increasingly recognized as the foundation for a healthy active lifestyle; however, robust research demonstrating its constitution, its relationship with health-related outcomes, and intervention strategies for its improvement remains to be completed. PMID- 26889583 TI - Corrective Equations to Self-Reported Height and Weight for Obesity Estimates Among U.S. Adults: NHANES 1999-2008. AB - PURPOSE: Estimating obesity prevalence using self-reported height and weight is an economic and effective method and is often used in national surveys. However, self-reporting of height and weight can involve misreporting of those variables and has been found to be associated to the size of the individual. This study investigated the biases in self-reporting of height and weight in the U.S. adult population and generated age-adjusted correction equations for self-reported height and weight separately for each ethnic group's specific height and weight quartile sample. Validity of the body mass index (BMI) classification calculated from corrected self-reported height and weight was also examined. METHOD: Data on self-reporting and direct measurement of height and weight from National Health and Nutrition Examination Survey 1999-2008 were analyzed. The final sample included 11,521 men and 10,905 nonpregnant women who were all U.S. citizens aged 20 years or older. RESULTS: A variation in misreporting of self-reported height and weight depended on the gender, ethnicity, age, and size of the individual. The results from sensitivity and specificity analyses showed that the BMI calculated from corrected values of self-reported height and weight provided more accurate estimations of overweight and obesity than did BMI calculated from self reported height and weight. CONCLUSION: In spite of some methodological concerns, the correction equation of self-reported height and weight generated in this study can be utilized as a method for quick assessment of estimating the obesity and overweight prevalence in the U.S. adult population. PMID- 26889584 TI - Locomotor, Heart-Rate, and Metabolic Power Characteristics of Youth Women's Field Hockey: Female Athletes in Motion (FAiM) Study. AB - PURPOSE: The purpose of this study was to quantify the locomotor, heart-rate, and metabolic power characteristics of high-level youth female field hockey matches. METHOD: Players from the U21 and U17 Canadian women's national teams were monitored during a 4-match test series using Global Positioning System technology. Position (forward, midfielder, defender) and age-group (U21, U17) comparisons were made using 2-way analyses of variance. RESULTS: Forwards played 12 min to 22 min fewer than midfielders and defenders and consequently had lower amounts of total, low-intensity, and moderate-intensity distances. Yet, forwards covered similar amounts of high-intensity running and sprinting distances despite the deficit in playing time. Only 10% to 15% of total distance was characterized by high-intensity running and sprinting, yet the majority of time was spent above 90% maximum heart rate. The distances in high, elevated, and maximal metabolic power categories were greater for U21 than U17 players. Yo-Yo Intermittent Recovery Test performance was related to high-intensity running and maximal metabolic power distance. CONCLUSIONS: The current findings highlight positional specificity as well as developmental gaps between age groups for youth female field hockey matches. These match characteristics should be used to assist in establishing appropriate training strategies through the developmental pathway and to assist player achievement to higher standards. PMID- 26889585 TI - A Qualitative Investigation of Need Fulfillment and Motivational Profiles in Collegiate Cheerleading. AB - PURPOSE: Cheerleading is one of the fastest-growing sports in the United States. Members of spirit squads play an undeniable role in developing a university's athletic image, and participation in cheer has the potential to affect adolescents and young adults in a positive manner. Yet, cheerleaders also encounter stereotypes, constant trivialization, and a relative lack of external rewards. Given this complex contextual and situational environment, the current investigation was designed to better understand why people are motivated to participate in collegiate cheerleading. More specifically, guided by the premises of self-determination theory (SDT), this study explored motivational profiles and basic psychological need satisfaction (i.e., competence, autonomy, and relatedness) across different contexts and situations that comprise the collegiate cheerleading environment. METHOD: Consistent with established guidelines for qualitative inquiry, 12 collegiate cheerleaders were interviewed at 3 separate time points during the course of 1 academic semester. RESULTS: Deductive and inductive qualitative analyses yielded 3 higher-order themes, including: (a) context specificity of basic psychological need satisfaction, (b) contribution of performance to motivation, and (c) occurrences of intrinsic motivation. CONCLUSIONS: These results highlighted the complex nature of motivation and basic psychological need fulfillment, including a potential synergism between relatedness and competence fulfillment as well as an influence of academics on sport motivation. These nuances add to the theoretical understanding of SDT and offer valuable insight for coaches and sport psychology professionals working with collegiate spirit squads. PMID- 26889586 TI - Prediction of VO2max in Children and Adolescents Using Exercise Testing and Physical Activity Questionnaire Data. AB - PURPOSE: The purpose of this study was to evaluate the use of a treadmill walk jog-run exercise test previously validated in adults and physical activity questionnaire data to estimate maximum oxygen consumption (VO2max) in boys (n = 62) and girls (n = 66) aged 12 to 17 years old. METHODS: Data were collected from Physical Activity Rating (PA-R) and Perceived Functional Ability (PFA) questionnaires, a walk-jog-run submaximal treadmill exercise test, and a maximal graded exercise test. RESULTS: Regression analysis resulted in the development of 2 models to predict VO2max. Submaximal exercise test data were used to build the following model (R2 = .73; SEE = 4.59 mL + kg(- 1) + min(- 1)): VO2max (mL + kg(- 1) + min(- 1)) = 26.890+(5.877 * Gender; 0 = female; 1 = male) - (0.782 * Body Mass Index [BMI])+(0.438 * PFA Score) +(2.712 * Treadmill Speed; mph) +(0.746 * Age) +(0.449 * PA-R Score). Maximal exercise test data were used to build the following model (R2 = .83; SEE = 3.63 mL + kg(- 1) + min(- 1)): VO2max (mL + kg(- 1) + min(- 1)) = 10.716+(1.334 * Maximal Treadmill Grade) +(5.203 * Treadmill Speed; mph) +(3.494 * Gender; 0 = female; 1 = male) - (0.413 * BMI) +(0.249 * PFA). CONCLUSIONS: The results of this study demonstrate, for the first time, that regression equations that use both exercise data and physical activity questionnaire data can accurately predict VO2max in youth. The submaximal and maximal exercise tests that use self-selected treadmill speeds can be used to assess cardiorespiratory fitness of youth with a wide range of fitness levels. PMID- 26889587 TI - Development and Testing of the Observational System for Recording Physical Activity in Children: Elementary School. AB - PURPOSE: This study describes the development and pilot testing of the Observational System for Recording Physical Activity-Elementary School (OSRAC-E) Version. METHOD: This system was developed to observe and document the levels and types of physical activity and physical and social contexts of physical activity in elementary school students during the school day. Interobserver agreement scores and summary data were calculated. RESULTS: All categories had Kappa statistics greater than .80, with the exception of the activity initiator category. Interobserver agreement scores were 96% or greater. The OSRAC-E was shown to be a reliable observation system that allows researchers to assess physical activity behaviors, the contexts of those behaviors, and the effectiveness of physical activity interventions in the school environment. CONCLUSION: The OSRAC-E can yield data with high interobserver reliability and provide relatively extensive contextual information about the physical activity of students in elementary schools. PMID- 26889588 TI - The Influence of Epoch Length on Physical Activity Patterns Varies by Child's Activity Level. AB - PURPOSE: Patterns of physical activity (PA) and sedentary time, including volume of bouted activity, are important health indicators. However, the effect of accelerometer epoch length on measurement of these patterns and associations with health outcomes in children remain unknown. METHOD: We measured activity patterns in 308 children (52% girls, age range = 8-11 years) using ActiGraph GT1M accelerometers with 15-s epochs and reintegrated to 60-s epochs. We calculated the volume (minutes per day) of moderate-to-vigorous PA (MVPA), sedentary time, light, moderate, and vigorous PA, as well as bouted MVPA and sedentary time (0-5 min, 5-10 min, 10-20 min, and > 20 min). RESULTS: The difference between 15-s and 60-s epochs was statistically significant for all outcomes; however, effect sizes were small or negligible in 30% of comparisons. Bias ranged from 1.9 min/day (total MVPA) to 102.7 min/day (0-5 min sedentary bouts). Regression-based estimates of bias and 95% limits of agreement illustrated that the magnitude, and in some cases, the direction, of between-epoch differences varied with activity level. Correlations with body mass index and cardiovascular fitness were similar for 15-s (r = -.19 to .20) and 60-s (r = -.16 to .29) epochs. Estimated 15-s data (predicted from 60-s) were similar to measured data and had similar relationships with health outcomes. CONCLUSION: Epoch length influences measurement of PA and sedentary patterns and the effect is modified by activity level. However, associations with health outcomes were similar and epoch differences can be adjusted. Future research should clarify the accuracy of different epoch lengths for measuring bouted activity and evaluate whether epoch length alters relationships with additional health outcomes. PMID- 26889590 TI - Maintained Stemness of Human Periodontal Ligament Stem Cells Isolated After Prolonged Storage of Extracted Teeth. AB - BACKGROUND: Human periodontal ligament stem cells (hPDLSCs) are readily accessible and represent a promising source of mesenchymal stem cells (MSCs) for therapies. For expected clinical applications of stem cell therapies, prolonged maintenance of stemness of hPDLSCs after storage is crucial. Likewise, optimization of cell quality and standardization of manufacturing protocols require evaluation of hPDLSC characteristics after storage. The aim of this study is to evaluate maintenance of stemness of hPDLSCs isolated after prolonged storage of the periodontal ligament (PDL), by studying: 1) growth and proliferation; 2) immunophenotypes; and 3) differentiation capabilities of hPDLSCs. METHODS: After extraction of premolars (N = 10), hPDLSCs were isolated immediately (n = 5) or after 1 week of tooth storage in growth medium (n = 5). Both groups were evaluated for: 1) colony formation; 2) proliferation; and 3) immunophenotypes. Osteogenic, adipogenic, and chondrogenic differentiation capabilities of hPDLSCs were evaluated at different times and by real-time polymerase chain reaction (PCR). RESULTS: Storing PDLs attached to teeth did not affect stemness of hPDLSCs. Colony formation and proliferation properties of hPDLSCs from PDLs harvested immediately after extraction or after storage for 1 week were comparable, and there were no significant differences in immunophenotypic markers between the two groups. Osteogenic, adipogenic, and chondrogenic differentiation capabilities of hPDLSCs were unaltered after PDL storage. Real-time PCR analyses indicated that the expression of: 1) osteogenic (runt-related transcription factor 2, alkaline phosphatase, and osteocalcin); 2) adipogenic (peroxisome proliferator-activated receptor-gamma and lipoprotein lipase); and 3) chondrogenic (aggrecan, collagen Type 2, and collagen Type 10) differentiation markers were similar for both groups. CONCLUSION: Within the limitations of the study, hPDLSCs stored for 1 week maintain the important characteristics of MSCs. PMID- 26889591 TI - Patenting drug delivery technology: tips for formulating practical and effective patent portfolio. PMID- 26889592 TI - The temporal trends of incidence, treatment, and in-hospital mortality of acute myocardial infarction over 15years in a Taiwanese population. AB - BACKGROUND: The study was conducted to examine the nationwide temporal trends of incidence, treatment, and short-term outcomes for acute myocardial infarction (AMI) over a 15-year period in Taiwan. METHODS: We identified patients who were hospitalized for incident AMI between 1997 and 2011 from the inpatient medical claim dataset of the National Health Insurance Research Database. Age- and sex adjusted incidence and in-hospital mortality rates were calculated for AMI, and separately for ST-segment elevation and non-ST-segment elevation myocardial infarction (STEMI and NSTEMI). RESULTS: A total of 144,634 patients were identified. The incidence rates (per 100,000 population) of AMI increased from 30 in 1997 to 42 in 2011, which was mainly driven by the increase of NSTEMI. The in hospital mortality rate after AMI decreased from 9.1% in 1997 to 6.5% in 2011, which was also driven by the case mortality rate for NSTEMI. Although the in hospital mortality rates significantly decreased from 7.3% to 5.1% between 1997 and 2003 for STEMI, it did not change significantly from 2004 to 2011. Moreover, AMI patients undergoing revascularization treatment, particularly PCI, was the most important independent predictor for improved in-hospital survival. CONCLUSION: The results of this study demonstrated a recent dramatic increase in the incidence rates and a decrease in short-term mortality in patients with NSTEMI; while the incidence and in-hospital morality of STEMI only modestly changed over time in Taiwan. Further quality improvement approaches for AMI prevention and treatment to favorably affect the incidence and outcomes from both major types of AMI are highly recommended. PMID- 26889593 TI - Detectable interleukin-9 plasma levels are associated with impaired cardiopulmonary functional capacity and all-cause mortality in patients with chronic heart failure. PMID- 26889595 TI - Coronary Sinus Reducer systemTM: A new therapeutic option in refractory angina patients unsuitable for revascularization. AB - A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris (RAP), a clinical condition characterized by severe angina despite optimal medical therapy and "no option" for a surgical or percutaneous revascularization. Although the relevant advance of both pharmaceutical and interventional treatments for patients affected by symptomatic coronary artery disease has greatly contributed to prolong survival, the increasing number of patients experimenting persistent and invalidating angina symptoms, highlights that quality of life of these patients has not been equally improved. Clinical limitations of the efficiency of conventional and relatively new approaches justify the search for new therapeutic options. In this review, we will focus on the epidemiology of RAP, and we will provide a brief update on the different options actually available to these patients with particular interest to an innovative device that narrow the coronary sinus: the Reducer system (Neovasc Inc., Richmond B.C., Canada). The efforts of present and future clinical studies will ultimately answer the question of whether this intriguing therapy is a suitable strategy for treatment of patients with RAP. PMID- 26889594 TI - Uhl's anomaly: Clinical spectrum and pathophysiology. PMID- 26889596 TI - Monitoring of high-dose fosfomycin guided by NT-proBNP. PMID- 26889597 TI - Enhanced oxidative stress is associated with sleep-disordered breathing and obesity in patients with heart failure. PMID- 26889598 TI - Papillary muscle or leaflet rupture of the tricuspid valve in arrhythmogenic cardiomyopathy. PMID- 26889599 TI - Transcatheter aortic valve replacement for severe aortic stenosis in dextrocardia with situs inversus: First reported case in the United States. PMID- 26889600 TI - Metabolic syndrome predicts plaque rupture in patients with acute myocardial infarction. An optical coherence study. PMID- 26889601 TI - The Palladium Way to N-Heteroacenes. AB - Novel synthetic methodologies allow increasingly efficient access to known organic materials, as well as the preparation of otherwise inaccessible species. Pd-catalyzed coupling of aromatic dihalides to ortho-diaminoarenes furnishes embedded stable N,N'-dihydropyrazines expediently and in often excellent yields. The embedded N,N'-dihydropyrazines can then be oxidized by MnO2 to give substituted azatetracenes, azapentacenes, azahexacenes, and azaheptacenes, which are soluble, processable, and stable. This powerful Pd-catalyzed methodology allows the preparation of azaacenes, including diaza-, tetraaza- and hexaazaacenes. In combination with a suitable Pd precursor, Buchwald-type biarylphosphines have been shown to give excellent results. Activated dihalides such as 2,3-dihaloquinoxalines are coupled easily under simplified conditions, whereas 2,3-dibromoacenes require more stringent conditions and advanced catalyst precursors. Pd catalysts effect the assembly of azaacenes with otherwise difficult to obtain substitution patterns. High yields and flexibility make this method most attractive. PMID- 26889602 TI - Proteomic analysis of native cerebellar iFGF14 complexes. AB - Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na(+) (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca(2+) (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14(-/-)) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (alpha) subunits or proteins previously reported to interact with Nav alpha subunits. In contrast, no Cav channel alpha or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14(-/-) mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes. PMID- 26889603 TI - Mental imagery of speech implicates two mechanisms of perceptual reactivation. AB - Sensory cortices can be activated without any external stimuli. Yet, it is still unclear how this perceptual reactivation occurs and which neural structures mediate this reconstruction process. In this study, we employed fMRI with mental imagery paradigms to investigate the neural networks involved in perceptual reactivation. Subjects performed two speech imagery tasks: articulation imagery (AI) and hearing imagery (HI). We found that AI induced greater activity in frontal-parietal sensorimotor systems, including sensorimotor cortex, subcentral (BA 43), middle frontal cortex (BA 46) and parietal operculum (PO), whereas HI showed stronger activation in regions that have been implicated in memory retrieval: middle frontal (BA 8), inferior parietal cortex and intraparietal sulcus. Moreover, posterior superior temporal sulcus (pSTS) and anterior superior temporal gyrus (aSTG) was activated more in AI compared with HI, suggesting that covert motor processes induced stronger perceptual reactivation in the auditory cortices. These results suggest that motor-to-perceptual transformation and memory retrieval act as two complementary mechanisms to internally reconstruct corresponding perceptual outcomes. These two mechanisms can serve as a neurocomputational foundation for predicting perceptual changes, either via a previously learned relationship between actions and their perceptual consequences or via stored perceptual experiences of stimulus and episodic or contextual regularity. PMID- 26889605 TI - Randomized, Placebo-Controlled Trial of Methyl B12 for Children with Autism. AB - OBJECTIVE: Children with autism spectrum disorder (ASD) have been reported to have reduced ability to methylate DNA and elevated markers of oxidative stress. We sought to determine if methyl B12, a key metabolic cofactor for cellular methylation reactions and antioxidant defense, could improve symptoms of ASD. METHODS: A total of 57 children with ASD were randomly assigned to 8 weeks of treatment with methyl B12 (75 MUg/kg) or saline placebo every 3 days in a subcutaneous injection. The primary outcome measure was overall improvement in symptoms of ASD as measured by the Clinical Global Impressions-Improvement (CGI I) score. Secondary outcome measures included changes in the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Laboratory measures of methionine methylation and antioxidant glutathione metabolism were assessed at baseline and 8 weeks. RESULTS: A total of 50 children (mean age 5.3 years, 79% male) completed the study. The primary outcome measure - the clinician rated CGI I score - was statistically significantly better (lower) in the methyl B12 group (2.4) than in the placebo group (3.1) (0.7 greater improvement in the methyl B12 group, 95% CI 1.2-0.2, p = 0.005). Clinical improvement among children treated with methyl B12 was positively correlated with increases in plasma methionine (p = 0.05), decreases in S-adenosyl-l-homocysteine (SAH) (p = 0.007) and improvements in the ratio of S-adenosylmethionine (SAM) to SAH (p = 0.007), indicating an improvement in cellular methylation capacity. No improvements were observed in the parent-rated ABC or SRS. CONCLUSIONS: Methyl B12 treatment improved clinician-rated symptoms of ASD that were correlated with improvements in measures of methionine metabolism and cellular methylation capacity. Clinical Trial Registry: Efficacy Study of Subcutaneous Methyl B12 in Children with Autism: NCT01039792 ( clinicaltrials.gov1 ). PMID- 26889606 TI - Topologically controlled tensile behaviour of braided prostheses for anterior cruciate ligaments. AB - Anterior cruciate ligament (ACL) is one of the most susceptible ligaments of the knee that can suffer injury. These ruptured ligaments can be treated through surgical intervention using a braided structure that either acts as a substitute graft in isolation or an augmentation device alongside the biological tissue. Therefore, the main objective of the research work is to present an analytical model for predicting the complete set of tensile properties of braided prosthesis consisting of multifilament strands based upon predefined braid geometry and constituent material properties. The model has also accounted for the kinematical changes under defined loading conditions. The research findings have been confirmed by making a comparison between the theoretical and experimental results. The tensile properties of braided prostheses predicted via analytical route matched reasonably well with the experimental results. PMID- 26889604 TI - A physiological signature of sound meaning in dementia. AB - The meaning of sensory objects is often behaviourally and biologically salient and decoding of semantic salience is potentially vulnerable in dementia. However, it remains unclear how sensory semantic processing is linked to physiological mechanisms for coding object salience and how that linkage is affected by neurodegenerative diseases. Here we addressed this issue using the paradigm of complex sounds. We used pupillometry to compare physiological responses to real versus synthetic nonverbal sounds in patients with canonical dementia syndromes (behavioural variant frontotemporal dementia - bvFTD, semantic dementia - SD; progressive nonfluent aphasia - PNFA; typical Alzheimer's disease - AD) relative to healthy older individuals. Nonverbal auditory semantic competence was assessed using a novel within-modality sound classification task and neuroanatomical associations of pupillary responses were assessed using voxel-based morphometry (VBM) of patients' brain MR images. After taking affective stimulus factors into account, patients with SD and AD showed significantly increased pupil responses to real versus synthetic sounds relative to healthy controls. The bvFTD, SD and AD groups had a nonverbal auditory semantic deficit relative to healthy controls and nonverbal auditory semantic performance was inversely correlated with the magnitude of the enhanced pupil response to real versus synthetic sounds across the patient cohort. A region of interest analysis demonstrated neuroanatomical associations of overall pupil reactivity and differential pupil reactivity to sound semantic content in superior colliculus and left anterior temporal cortex respectively. Our findings suggest that autonomic coding of auditory semantic ambiguity in the setting of a damaged semantic system may constitute a novel physiological signature of neurodegenerative diseases. PMID- 26889607 TI - Hydrogen bonding to carbonyl oxygen of nitrogen-pyramidalized amide - detection of pyramidalization direction preference by vibrational circular dichroism spectroscopy. AB - Nitrogen-pyramidalization of amide increases electron density on nitrogen and decreases that on carbonyl oxygen. We identified hydrogen-bonding to carbonyl of nitrogen-pyramidalized bicyclic beta-proline derivatives by crystallography, and by NMR and vibrational circular dichroism (VCD) spectroscopy in solution. Such hydrogen-bonding can switch the preferred nitrogen-pyramidalization direction, as detected by VCD spectroscopy. PMID- 26889609 TI - Jordanian Nurses' involvement in health policy: perceived benefits and barriers. AB - AIM: To examine (1) the level of involvement of Jordanian nurses in health policy development and (2) perceived benefits, barriers and impacts on health outcomes of involvement in health policy process. BACKGROUND: Lack of nurses' political involvement may result in self-serving policies by policymakers who are in power and passing policies that are less than optimum. METHOD: A descriptive cross sectional design was adopted in this study. A convenience sample of 231 nurses was recruited with a response rate of 77%. The instrument of Registered Nurses' Involvement in Health Policies was used in this study. RESULTS: The results revealed that participants were most frequently involved in the health policy activity 'voting for a candidate or a health policy proposal'. The mean scores for involvement of participants as nurses and as citizens were low. The most perceived frequent barrier to involvement in health policy was lack of time. DISCUSSION: The low rate of Jordanian nurses' involvement in health policy could be explained by the fact that most participants had family roles in addition to work roles, which might leave little time for health policy activities. Lack of mentoring for nurses by nursing leaders could also negatively affect their involvement in health policy development. CONCLUSION AND IMPLICATIONS FOR HEALTH POLICY: Results of this study could be baseline information for Jordanian nurse leaders to enhance the level of nurses' involvement in health policy development. Such findings could also add knowledge to the existing literature about nurses' involvement in health policy. PMID- 26889608 TI - Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia. AB - Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009 2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB. PMID- 26889610 TI - Feasibility and Utility of the Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing. PMID- 26889611 TI - The Effect of Medicinal Cannabis on Pain and Quality-of-Life Outcomes in Chronic Pain: A Prospective Open-label Study. AB - OBJECTIVES: The objective of this prospective, open-label study was to determine the long-term effect of medicinal cannabis treatment on pain and functional outcomes in participants with treatment-resistant chronic pain. PATIENTS AND METHODS: The primary outcome was the change in the pain symptom score on the S TOPS (Treatment Outcomes in Pain Survey-Short Form) questionnaire at the 6-month follow-up in an intent-to-treat population. Secondary outcomes included the change in S-TOPS physical, social, and emotional disability scales, the pain severity, and pain interference on the Brief Pain Inventory, sleep problems, and the change in opioid consumption. RESULTS: A total of 274 participants were approved for treatment; complete baseline data were available for 206 (intent-to treat), and complete follow-up data for 176 participants. At follow-up, the pain symptom score improved from median 83.3 (95% confidence interval [CI], 79.2-87.5) to 75.0 (95% CI, 70.8-79.2) (P<0.001). The pain severity score (7.50 [95% CI, 6.75-7.75] to 6.25 [95% CI, 5.75-6.75]) and the pain interference score (8.14 [95% CI, 7.28-8.43] to 6.71 [95% CI, 6.14-7.14]) improved (both P<0.001), together with most social and emotional disability scores. Opioid consumption at follow-up decreased by 44% (P<0.001). Serious adverse effects led to treatment discontinuation in 2 participants. DISCUSSION: The treatment of chronic pain with medicinal cannabis in this open-label, prospective cohort resulted in improved pain and functional outcomes, and a significant reduction in opioid use. Results suggest long-term benefit of cannabis treatment in this group of patients, but the study's noncontrolled nature should be considered when extrapolating the results. PMID- 26889612 TI - Isometric Exercise Above but not Below an Individual's Pain Threshold Influences Pain Perception in People With Lateral Epicondylalgia. AB - OBJECTIVE: To examine the acute effects of isometric exercise of different intensities on pain perception in individuals with chronic lateral epicondylalgia. MATERIALS AND METHODS: Participants performed 3 experimental tasks completed in a randomized order on separate days: control (no exercise) and isometric wrist extension (10*15 s) at load 20% below (infrathreshold), and 20% above (suprathreshold) an individual's pain threshold. Self-reported pain intensity (11-point numeric rating scales), pressure pain threshold, and pain free grip were assessed by a blinded examiner before, immediately after, and 30 minutes after task performance. Relation analysis between pain ratings and clinical variables, including pain and disability and kinesiophobia was performed. RESULTS: Twenty-four individuals with unilateral lateral epicondylalgia of median 3-month duration participated. Pain intensity during contraction was significantly higher during suprathreshold exercise than infrathreshold exercise (mean difference in numeric rating scale 1.0; 95% confidence interval, 0.4-1.5; P=0.002). Pain intensity during suprathreshold exercise was significantly correlated with pain and disability (R=0.435, P=0.034) and kinesiophobia (R=0.556, P=0.005). Pain intensity was significantly higher immediately after performance of suprathreshold exercise, compared with infrathreshold exercise (P=0.01) and control (P<0.001) conditions, whereas infrathreshold exercise and control conditions were comparable. Thirty minutes later, pain levels remained significantly higher for suprathreshold exercise compared with infrathreshold exercise (P=0.043). Pressure pain threshold and pain free grip showed no significant effects of time, condition, or time*condition (P>0.05). DISCUSSION: Individuals with lateral epicondylalgia demonstrated increased pain intensity after an acute bout of isometric exercise performed at an intensity above, but not below, their individual pain threshold. Further investigation is needed to determine whether measurement of an individual's exercise induced pain threshold may be important in reducing symptom flares associated with exercise. PMID- 26889613 TI - Differing Psychologically Derived Clusters in People With Chronic Low Back Pain are Associated With Different Multidimensional Profiles. AB - OBJECTIVES: To explore the existence of subgroups in a cohort with chronic low back pain (n=294) based upon data from multiple psychological questionnaires, and profile subgroups on data from multiple dimensions. METHODS: Psychological questionnaires considered as indicator variables entered into latent class analysis included: Depression, Anxiety, Stress scales, Thought Suppression and Behavioural Endurance subscales (Avoidance Endurance questionnaire), Chronic Pain Acceptance Questionnaire (short-form), Pain Catastrophising Scale, Pain Self Efficacy Questionnaire, and Fear-Avoidance Beliefs Questionnaire. Multidimensional profiling of derived clusters included: demographics, pain characteristics, pain responses to movement, behaviors associated with pain, body perception, pain sensitivity, and health and lifestyle factors. RESULTS: Three clusters were derived. Cluster 1 (23.5%) was characterized by low Cognitive and Affective Questionnaire scores, with the exception of fear-avoidance beliefs. Cluster 2 (58.8%) was characterized by relatively elevated thought suppression, catastrophizing, and fear-avoidance beliefs, but lower pain self-efficacy, depression, anxiety, and stress. Cluster 3 (17.7%) had the highest scores across cognitive and affective questionnaires.Cluster 1 reported significantly lower pain intensity and bothersomeness than other clusters. Disability, stressful life events, and low back region perceptual distortion increased progressively from cluster 1 to cluster 3, whereas mindfulness progressively decreased. Clusters 2 and 3 had more people with an increase in pain following repeated forward and backward spinal bending, and more people with increasing pain following bending, than cluster 1. Cluster 3 had significantly greater lumbar pressure pain sensitivity, more undiagnosed comorbid symptoms, and more widespread pain than other clusters. DISCUSSION: Clinical implications relating to presentations of each cluster are postulated. PMID- 26889614 TI - Chronic Pain Following Motor Vehicle Collision: A Systematic Review of Outcomes Associated With Seeking or Receiving Compensation. AB - OBJECTIVE: Motor vehicle collisions (MVC) are a major cause of injury, which frequently lead to chronic pain and prolonged disability. Several studies have found that seeking or receiving financial compensation following MVC leads to poorer recovery and worse pain. We evaluated the evidence for the relationship between compensation and chronic pain following MVC within a biopsychosocial framework. METHOD: A comprehensive search of 5 computerized databases was conducted. Methodological quality was evaluated independently by 2 researchers according to formal criteria, and discrepancies were resolved with a third reviewer. RESULTS: We identified 5619 studies, from which 230 full-text articles were retrieved and 27 studies were retained for appraisal. A third of studies (37%) were of low quality, and 44% did not measure or control for factors such as injury severity or preinjury pain and disability. Most studies (70%) reported adverse outcomes, including all of the highest quality studies. Engagement with compensation systems was related to more prevalent self-reported chronic pain, mental health disorders, and reduced return to work. Recovery was poorer when fault was attributed to another, or when a lawyer was involved. Five studies compared Tort "common law" and No-Fault schemes directly and concluded that Tort claimants had poorer recovery. CONCLUSIONS: Although causal relationships cannot be assumed, the findings imply that aspects of loss, injustice, and secondary mental health outcomes lead to chronic pain following MVC. Further robust prospective research is required to understand the complex relationship between compensation systems and pain following road trauma, particularly the role of secondary mental health outcomes. PMID- 26889616 TI - Randomized Sham-controlled Double-Blind Multicenter Clinical Trial to Ascertain the Effect of Percutaneous Radiofrequency Treatment for Sacroiliac Joint Pain: Three-month Results. AB - OBJECTIVES: To investigate the effect of a percutaneous radiofrequency (RF) heat lesion compared with a sham procedure, applied to the lateral branches of L5, S1, S2, S3, and S4 nerve roots. MATERIALS AND METHODS: Sixty patients aged 18 years and above with a medical history and physical examination suggestive for sacroiliac joint pain and a reduction of 2 or more on a numerical rating scale (NRS, 0 to 10) after a sacroiliac joint test block were included in this study. Treatment group: percutaneous RF heat lesion at the lateral branches of S1, S2, S3, and S4 nerve roots and the posterior ramus dorsalis of L5; sham group: same procedure as the treatment group except for the RF heat lesion. PRIMARY OUTCOME MEASURE: pain reduction (NRS). Secondary outcome measure: Global Perceived Effect. RESULTS: No statistically significant differences in pain level over time between the groups (Group*Period) (F1,58=0.353; P=0.56) nor within the treatment Group (F1,58=0.212; P=0.65) were found. The Period factor, however, yielded a significant difference (F1,58=61.67; P<0.001), that is, when pooled together the mean pain level of the patients was significantly reduced at T1 compared with T0. In the crossover group, 42.1% experienced a reduction in NRS of 2 or more at 1 month (P=0.65). No statistically significant difference in satisfaction over time between the groups was found (F1,50=2.1; P=0.15). The independent factors Group (F1,50=2.02; P=0.16) and Period (F1,50=0.95; P=0.33) also showed no statistically significant difference. The same applies to recovery: no statistically significant Group*Period effect (F1,51=0.09; P=0.77) was found, neither an effect of Group (F1,51=0.004; P=0.95) nor of Period (F1,51=0.27; P=0.60). DISCUSSION: The hypothesis of no difference in pain reduction or in Global Perceived Effect between the treatment and sham group cannot be rejected. LEVEL OF EVIDENCE: Level 1A. PMID- 26889615 TI - Multiple Levels of Suffering: Discrimination in Health-Care Settings is Associated With Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease. AB - OBJECTIVE: People living with sickle cell disease (SCD) experience severe episodic and chronic pain and frequently report poor interpersonal treatment within health-care settings. In this particularly relevant context, we examined the relationship between perceived discrimination and both clinical and laboratory pain. METHODS: Seventy-one individuals with SCD provided self-reports of experiences with discrimination in health-care settings and clinical pain severity, and completed a psychophysical pain testing battery in the laboratory. RESULTS: Discrimination in health-care settings was correlated with greater clinical pain severity and enhanced sensitivity to multiple laboratory-induced pain measures, as well as stress, depression, and sleep. After controlling for relevant covariates, discrimination remained a significant predictor of mechanical temporal summation (a marker of central pain facilitation), but not clinical pain severity or suprathreshold heat pain response. Furthermore, a significant interaction between experience with discrimination and clinical pain severity was associated with mechanical temporal summation; increased experience with discrimination was associated with an increased correlation between clinical pain severity and temporal summation of pain. DISCUSSION: Perceived discrimination within health-care settings was associated with pain facilitation. These findings suggest that discrimination may be related to increased central sensitization among SCD patients, and more broadly that health-care social environments may interact with pain pathophysiology. PMID- 26889617 TI - Efficacy of Cabbage Leaf Wraps in the Treatment of Symptomatic Osteoarthritis of the Knee: A Randomized Controlled Trial. AB - OBJECTIVES: Osteoarthritis (OA) of the knee is one of the most common chronic diseases among older adults. This study aimed to test the effects of cabbage leaf wraps (CLWs) in the treatment of symptomatic OA. METHODS: Patients with OA of the knee at stages II to III (Kellgren-Lawrence) were randomly assigned to 4 weeks of treatment with CLWs (daily for at least 2h), topical pain gel (TPG) (10 mg diclofenac/g, at least once daily), or usual care (UC). The primary outcome measure was pain intensity (VAS) after 4 weeks. Secondary outcomes included functional disability Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life (SF-36), self-efficacy (Arthritis Self-Efficacy Scale D), physical function (30 s Chair Stand Test), pressure pain sensitivity (PPT), satisfaction, and safety after 4 and 12 weeks. RESULTS: In total, 81 patients were included in this study (42 women, 65.9+/-10.3 y). After 4 weeks patients in the CLW group reported significantly less pain compared with those in the UC group (difference, -12.1; 95% [confidence interval] CI, -23.1, -1.0; P=0.033) but not when compared with the TPG group (difference, -8.6; 95% CI, -21.5, 4.4; P=0.190). Significant effects were also found in WOMAC, SF-36, 30-second Chair Stand Test, and PPT scores in the CLW group compared with the UC group. Compared with TPG, effects from CLW were found for WOMAC after 4 weeks and for quality of life after 12 weeks. Patients were satisfied with both active interventions, and except for 2 adverse events in both groups the applications were well tolerated. CONCLUSIONS: CLWs are more effective for knee OA than UC, but not compared with diclofenac gel. Therefore, they might be recommended for patients with OA of the knee. Further research is warranted. PMID- 26889618 TI - Assessment of Procedural Pain in Children Using Analgesia Nociception Index: A Pilot Study. AB - OBJECTIVES: The Analgesia Nociception Index (ANI), based on heart rate (HR) variability analysis, is known to decrease after a painful stimulus during surgery under general anesthesia in adults. It is measured continuously and noninvasively. We studied ANI response to procedural pain in a pediatric population and ANI measurement's feasibility in this context, across age. METHODS: A prospective, noninterventional pilot study was performed. All children (between 6 mo and under 18 y) undergoing muscle biopsy conducted under analgesia and light sedation were included. Medical staff was blind to the ANI monitor. HR and ANI were recorded and analyzed during 2 periods: T1 before incision and T2 after incision. Pain was assessed by the FLACC scale at T2. We observed ANI and HR variations after incision. ANI, HR, and FLACC were compared between children younger or older than 6 years. Enrollment or technical issues were reported. RESULTS: A total of 26 children were included (median age, 6 y; ranging from 6 mo to 16 y; 16 male). ANI decreased from T1 to T2. HR, ANI, or FLACC values were not different in children younger or older than 6 years. No parents or children refused to take part in the study. No technical issues was reported. DISCUSSION: In this pilot study, ANI measurement seems relevant in pediatric procedural pain, across age. Further studies are needed to confirm these results. PMID- 26889619 TI - The Association Between Chronic Pain and Cardiac Disease: A Cross-sectional Population Study. AB - OBJECTIVES: Chronic pain may increase the risk of cardiac disease, but the extent to which confounding variables account for this association has yet to be satisfactorily established. This study aims to examine the possibility of an independent association between these 2 variables. METHODS: We applied logistic regression analysis to data from 8596 adults surveyed in a population study of the health of the population of England. The association between cardiac disease (angina and/or myocardial infarction) and chronic pain (pain lasting >3 months) was explored, taking account of 10 potentially confounding variables including the regular use of nonsteroidal anti-inflammatory drugs. RESULTS: Participants reporting chronic pain (n=3023) were more likely to experience cardiac disease than those without pain: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.15-2.07. Subsets of participants fulfilling various criteria for high-intensity chronic pain demonstrated stronger associations with cardiac disease suggesting a "dose-response" element to the relationship: chronic widespread pain (OR, 3.3; 95% CI, 1.42-7.68); higher-disability chronic pain (OR, 2.35; 95% CI, 1.71-3.23); and higher average chronic pain score (OR, 1.95; 95% CI, 1.40-2.71). Adjustment for regular prescription of nonsteroidal anti-inflammatory drugs did not reduce the association of chronic pain with cardiac disease. DISCUSSION: Patients reporting chronic pain, in particular those most severely affected, may be at significantly increased risk of cardiac disease. Future studies should focus on determining whether reducing the impact of chronic pain can improve cardiac health. PMID- 26889621 TI - Quadriceps Muscle Strength Correlates With Serum Vitamin D and Knee Pain in Knee Osteoarthritis. AB - BACKGROUND: Quadriceps muscle weakness and vitamin D deficiency are associated with knee osteoarthritis (KOA). This study aimed to investigate the relationship between quadriceps muscle strength (QMS) and vitamin D in KOA. METHODS: Patients with KOA aged 40 years and above were studied. QMS was assessed by the dynanometry method and serum 25-hydroxyvitamin D (25-OHD) by the ELISA method. Serum 25-OHD<20 ng/mL was considered as a deficiency. The intensity of knee pain was determined by the Western Ontario and McMaster Universities Osteoarthritis Index Pain Scale. The Pearson test was used for correlation analysis between QMS and serum 25-OHD as well as knee pain. RESULTS: A total of 92 patients (female, 80%) with a mean age of 49.6+/-11.7 years were studied. QMS was correlated positively with serum 25-OHD (r=0.304, r=9.24%, P=0.005) and negatively with knee pain (r=-0.232, r=5.3%, P=0.034). After adjustment for age, sex, and body mass index, the positive correlation increased to a higher level (r=0.496, r=24.9%, P=0.01). For each 1 ng/mL increase in serum 25-OHD, the value of QMS increased by 14.2%+/-3.5% (P=0.014). There was no significant correlation between serum 25-OHD and knee pain (P=0.13). CONCLUSIONS: These findings demonstrated a significant correlation between QMS with both serum vitamin D and knee pain, indicating a confounding role for quadriceps muscle in the association between serum vitamin D and osteoarthritis knee pain. On the basis of the findings of this study, vitamin D supplementation may affect pain by strengthening quadriceps muscle in KOA. PMID- 26889622 TI - Assessing Pain Anxiety in Adolescents: Further Evidence for the Utility of the Child Pain Anxiety Symptoms Scale. AB - OBJECTIVES: Emotional responses to pain are known to play an important role in the development and maintenance of pain. To better understand the role that pain anxiety plays in chronic pain, as well as to evaluate treatments that might treat it effectively, reliable and valid measures of pain anxiety are needed. Thus, the aim of this study was to provide additional evidence regarding the psychometric properties of the Child Pain Anxiety Symptoms Scale (CPASS) in a sample of adolescents. METHODS: A total of 357 adolescents ages 12 to 19 years completed measures of pain anxiety (CPASS), pain-related catastrophizing (PCS-C), anxiety sensitivity (CASI), and sleep quality (NRS-Sleep). We used confirmatory factor analyses to evaluate the factor structure of CPASS items. We also tested the reliability and the validity of CPASS scores. RESULTS: Confirmatory factor analyses suggested a 4-factor structure with a single higher-order factor (CFI=0.91, TLI=0.95, RMSEA=0.078). The total score of CPASS showed good internal consistency (alpha=0.87) and adequate validity as evidenced by (1) moderate to high correlations between CPASS-PCS-C (r=0.74, P<0.001) and CPASS-CASI (r=0.48, P<0.001) and (2) the magnitude of the correlations between CPASS-PCS-C and CPASS CASI being significantly greater than that between CPASS and NRS-Sleep (z=14.70 and 8.96, respectively; P<0.001). DISCUSSION: The findings support the reliability and the validity of CPASS as a measure of pain-related anxiety in adolescents. PMID- 26889620 TI - Affect and Low Back Pain: More to Consider Than the Influence of Negative Affect Alone. AB - OBJECTIVES: Affect balance style, a measure of trait positive affect (PA) and negative affect (NA), is predictive of pain and functioning in fibromyalgia and healthy individuals. The purpose of this study was to evaluate the distribution of affect balance styles and the relationship between these styles and clinical factors in low back pain. METHODS: In this cross-sectional study, patients with low back pain (N=443) completed questionnaires and were categorized as having 1 of 4 distinct affect balance styles: Healthy (high levels of PA and low levels of NA), Low (low PA/low NA), Reactive (high PA/high NA), and Depressive (low PA/high NA). Comparisons between groups were made in regard to pain, functioning, and psychiatric comorbidity. RESULTS: High NA was observed in 63% (n=281), whereas low PA was present in 81% (n=359). We found that having a Depressive style was associated with greater pain severity, increased odds for comorbid fibromyalgia, and worse functioning compared with having a Healthy or Low style. Yet, those with a Low style were at increased risk for depression compared with a Healthy style, whereas patients with a Reactive style had similar levels of pain, functioning, and depression as those with a Healthy affective style. CONCLUSIONS: Our study revealed that there are important differences between trait affect balance styles in regard to pain, mood, and functioning in low back pain. Findings related to Reactive and Low affective styles suggest that relationships between affect, pain, and disability in low back pain extend beyond considering NA alone. PMID- 26889623 TI - Does Magnesium Sulfate as an Adjuvant of Local Anesthetics Facilitate Better Effect of Perineural Nerve Blocks?: A Meta-analysis of Randomized Controlled Trials. AB - OBJECTIVES: To investigate the efficacy and safety of magnesium sulfate as an adjuvant of local anesthetics in perineural nerve blocks. MATERIALS AND METHODS: Randomized controlled trials studying the effect and safety of magnesium sulfate in perineural nerve blocks were retrieved from online databases. The mean difference (MD), risk ratio, and their corresponding 95% confidence intervals (CIs) were calculated using RevMan 5.3 statistical software. RESULTS: Seven trials evaluating 493 patients were included. The pooled results from our meta analysis showed that a combination of magnesium sulfate and local anesthetics in nerve blocks could result in longer postoperative duration time of analgesia (MD=124.66; 95% CI, 65.09-184.23; P<0.0001), longer duration time of sensory (MD=106.69; 95% CI, 60.93-152.45; P<0.00001) and motor block (MD=89.95; 95% CI, 50.89-129.00; P<0.0001). In addition, magnesium sulfate in nerve blocks was also associated with significantly quick onset of motor block (MD=-1.17; 95% CI, -1.73 to -0.60; P<0.0001). For onset time of sensory block, number of patients requiring supplementary analgesics, and incidence of postoperative nausea and vomiting, no statistically differences were observed between the 2 groups. DISCUSSION: The present study suggests that combined magnesium sulfate and local anesthetics in perineural nerve blocks provided better analgesic efficacy. For it prolongs the postoperative duration time of analgesia, sensory and motor block without increasing the short-term side effects. Magnesium sulfate may be a promising analgesic for perineural nerve blocks, but further studies are required to validate our results. PMID- 26889624 TI - Implant Vertical Fractures Provoked by Laboratory Procedures: A Finite Element Analysis Inspired from Clinical Cases. AB - PURPOSE: To investigate the causes for internal implant fractures, which is suggested to be one of the reasons for marginal bone loss. MATERIALS AND METHODS: From a 14-year database of 6051 implants, 10 single implant vertical fractures were identified and the abutments were all castable abutments. The abutments presented contamination and irregularities at the internal connecting areas. The hypothesis was that perfect fit was disturbed by laboratory polishing procedures, and finite element analysis (FEA) using overcorrected and undercorrected castable abutment models were created and tested against a perfect fit model. RESULTS: The results from the FEA presented that both overcorrected and undercorrected models presented nonuniform excessive plastic strain distribution in the neck portion of the implants where clinically an implant fracture was noted. CONCLUSIONS: The results suggested that laboratory procedures could induce plastic strain of the implant-abutment complex, which increases the risk of fracture. PMID- 26889625 TI - Trends in Liver Transplantation in Hepatitis C Virus-Infected Persons, United States. PMID- 26889626 TI - Towards a revised Spetzler-Martin arteriovenous malformation grading scale: redefining the "eloquent brain areas". PMID- 26889628 TI - Risk factors and sources of foodborne hepatitis E virus infection in the United States. AB - Hepatitis E virus (HEV) is an important human pathogen with pigs and other species serving as natural animal reservoirs. Ample evidence documents sporadic cases of hepatitis E acquired via consumption of undercooked meat. Chronic hepatitis E cases in immunosuppressed individuals are mostly caused by zoonotic HEV of swine origin. We report here the identification of genotype 3 HEV from non liver commercial pork from local grocery stores in southwest Virginia, and association of HEV seropositivity to the consumption of undercooked meat in healthy young adults at a university in the United States. These results raise concerns about foodborne HEV transmission in the United States. J. Med. Virol. 88:1641-1645, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26889627 TI - Perioperative dexmedetomidine for acute pain after abdominal surgery in adults. AB - BACKGROUND: Acute postoperative pain is still an issue in patients undergoing abdominal surgery. Postoperative pain and side effects of analgesic treatment, in particular those of opioids, need to be minimized. Opioid-sparing analgesics, possibly including dexmedetomidine, seem a promising avenue by which to improve postoperative outcomes. OBJECTIVES: Our primary aim was to determine the analgesic efficacy and opioid-sparing effect of perioperative dexmedetomidine for acute pain after abdominal surgery in adults.Secondary aims were to establish effects of dexmedetomidine on postoperative nausea and vomiting (PONV), gastrointestinal function and mobilization, together with the side effect profile of dexmedetomidine. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Institute for Scientific Information (ISI), Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL), and reference lists of articles to May 2014. We searched the Science Citation Index, ClinicalTrials.gov and Current Controlled Trials, and we contacted pharmaceutical companies to identify unpublished and ongoing studies. We applied no language restrictions. We reran the search in May 2015 and found nine studies of interest. We will deal with the studies of interest when we update the review. SELECTION CRITERIA: We included randomized, controlled trials of perioperative dexmedetomidine versus placebo or other drug during abdominal surgery in adults. Trials included one of the following outcomes: amount of 'rescue' opioid, postoperative pain, time to 'rescue' analgesia, participants requiring 'rescue' analgesia, postoperative sedation, PONV, time to first passage of flatus and stool or time to first out-of-bed mobilization. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles and abstracts for eligibility. We retrieved full trial reports if necessary, and we extracted relevant data from the included studies using a data collection form and assessed risk of bias. We resolved disagreements by discussion with the third review author. We sought additional information of relevance for risk of bias assessment or extraction of data by contacting study authors or, if necessary, co-authors from present or former studies. MAIN RESULTS: Our systematic review included seven studies with a total of 492 participants. We included 422 participants in our analysis. Thirteen studies are awaiting classification. For the comparison dexmedetomidine versus placebo (six studies, 402 participants), most studies found a reduction in 'rescue' opioid consumption in the first 24 hours after surgery, together with in general no clinically important differences in postoperative pain (visual analogue scale (VAS) 0 to 100 mm, where 0 = no pain and 100 = worst imaginable pain) in the first 24 hours after surgery - except for one study (80 participants) with a reduction in VAS pain at two hours after surgery in favour of dexmedetomidine, with a mean difference of -30.00 mm (95% confidence interval (CI) -38.25 to 21.75). As the result of substantial heterogeneity, pooling of data in statistical meta-analyses was not appropriate. The quality of evidence was very low for our primary outcomes because of imprecision of results and risk of bias. Regarding our secondary aims, evidence was too scant in general to allow robust conclusions, or the estimates too imprecise or of poor methodological quality. Regarding adverse effects, low quality data (one study, 80 participants) suggest that the proportion of participants with hypotension requiring intervention was slightly higher in the high-dose dexmedetomidine group with a risk ratio of 2.50 (95% CI 0.94 to 6.66), but lower doses of dexmedetomidine led to no differences compared with control. Evidence for the comparison dexmedetomidine versus fentanyl was insufficient to permit robust conclusions (one study, 20 participants). AUTHORS' CONCLUSIONS: Dexmedetomidine, when administered perioperatively for acute pain after abdominal surgery in adults, seemed to have some opioid-sparing effect together with in general no important differences in postoperative pain when compared with placebo. However the quality of the evidence was very low as the result of imprecision, methodological limitations and substantial heterogeneity among the seven included studies. The clinical importance for patients is uncertain, in as much as the influence of dexmedetomidine on patient-important outcomes such as gastrointestinal function, mobilization and adverse effects could not be satisfactorily determined. All included studies were relatively small, and publication bias could not be ruled out. Applicability of evidence was limited to middle-aged participants who were relatively free of co-morbidity and were undergoing elective abdominal surgery. A potential bias was a considerable quantity of unobtainable data from studies with mixed surgery. To detect and investigate patient-important outcomes, larger studies with longer periods of follow-up are needed. PMID- 26889629 TI - Quantitative STIR of muscle for monitoring nerve regeneration. AB - PURPOSE: To assess whether short tau inversion recovery (STIR) MRI sequences can provide a tool for monitoring peripheral nerve regeneration, by comparing signal intensity changes in reinnervated muscle over time, and to determine potential clinical time points for monitoring. MATERIALS AND METHODS: For this prospective study, 29 patients with complete traumatic transection of the ulnar or median nerves in the forearm were followed up to 45 months postsurgery. Standardized 1.5 Tesla STIR-MRI scans of hand muscles were obtained at fixed time intervals. Muscle signal intensities were measured semi-quantitatively and correlated to functional outcome. RESULTS: For the patients with good function recovery, mean signal intensity ratios of 1.179 +/- 0.039, 1.304 +/- 0.180, 1.154 +/- 0.121, 1.105 +/- 0.046 and 1.038 +/- 0.047 were found at 1-, 3-, 6-, 9-, and 12-month follow-up, respectively. In the group with poor function recovery, ratios of 1.240 +/- 0.069, 1.374 +/- 0.144, 1.407 +/- 0.127, 1.386 +/- 0.128 and 1.316 +/- 0.116 were found. Comparing the groups showed significant differences from 6 months onward (P < 0.001), with normalizing signal intensities in the group with good function recovery and sustained elevated signal intensity in the group with poor function recovery. CONCLUSION: MRI of muscle can be used as a tool for monitoring motor nerve regeneration, by comparing STIR muscle signal intensities over time. A decrease in signal intensity ratio of 50% (as compared to the initial increase) seems to predict good function recovery. Long-term follow-up shows that STIR MRI can be used for at least 15 months after nerve transection to differentiate between denervated and (re)innervated muscles. J. Magn. Reson. Imaging 2016;44:401-410. PMID- 26889630 TI - Reception of Communicative Functions of Prosody in Hypokinetic Dysarthria due to Parkinson's Disease. AB - BACKGROUND: Mapping adequacy of receptive prosodic abilities in speakers with hypokinetic dysarthria due to Parkinson's disease (PD) is useful, because therapy of disturbed production of prosody relies on adequate reception of prosody. There is evidence for a deficit of reception of emotional prosody in PD. OBJECTIVE: The present study aims at presenting a comprehensive picture of the reception of various communicative functions of prosody in hypokinetic dysarthria due to PD. METHODS: We assessed perception (using a discrimination task) and comprehension (using an identification task) of five communicative functions of Dutch prosody (lexical stress, boundary marking, focus, sentence mode, and emotional prosody) in a group of adults with hypokinetic dysarthria due to PD (n = 22) and a gender and age matched group of unimpaired adults (n = 22). We also investigated the relationship between age and global test score, and the effect of perception and comprehension subtest sequence on the global test score. RESULTS: Between groups, no significant differences in receptive prosodic abilities were found. Within both groups, the comprehension subtest was significantly more difficult than the perception subtest, and there was a significant negative correlation between age and global test score. No subtest sequence effect could be demonstrated. CONCLUSIONS: Considering that the older speakers with hypokinetic dysarthria due to PD had receptive prosodic skills inferior to those of the younger speakers, notwithstanding apparently intact cognition and hearing, the findings suggest that age is a factor to be reckoned with in prosody assessment and management in this population. PMID- 26889631 TI - Profile of Neuropsychiatric Symptoms in Parkinson's Disease: Surgical Candidates Compared to Controls. AB - BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson's disease (PD) and motor complications of dopaminergic treatment. Whether STN-DBS should be considered when PD patients experience neuropsychiatric symptoms is controversial. Lack of systematic behavioral evaluation at baseline hampers the understanding of postoperative neuropsychiatric outcomes. OBJECTIVE: This study compares the behavioral profile of a surgical population to that in general PD. METHODS: Single center data from 234 PD surgical candidates were compared to data from 260 non-demented PD patients consulting in 13 PD expert centers at different stages of disease. The latter were considered representative of the general PD population. Neuropsychiatric symptoms were assessed using the Ardouin Scale of Behavior in PD, a guided interview quantifying changes in severity of 21 neuropsychiatric symptoms, classified into psychic non-motor fluctuations, hypo- and hyperdopaminergic behaviors. Multivariate analyses were performed to study differences in behavioral items between the two groups. RESULTS: Surgical candidates were younger, had longer disease duration and used significantly higher doses of dopaminergic drugs. After adjustment for covariates, dopaminergic addiction (OR 10.83; p = 0.002), nocturnal hyperactivity (OR 1.87; p = 0.04), excessive hobbyism (OR 2.37; p = 0.008), "excess in motivation" (OR 4.02; p < .001), psychic OFF (2.87; p < 0.001) and psychic ON (2.10; p = 0.001) fluctuations were more frequent in the surgical candidates. Depressed mood prevailed in the general PD population (OR 0.53; p = 0.045). CONCLUSION: Behavioral complications of dopaminergic treatment are frequent in PD patients candidates for STN-DBS. They cannot be considered as contraindications for STN DBS but must be taken into account in postoperative management. PMID- 26889632 TI - Safinamide as Add-On Therapy to Levodopa in Mid- to Late-Stage Parkinson's Disease Fluctuating Patients: Post hoc Analyses of Studies 016 and SETTLE. AB - BACKGROUND: Studies 016 and SETTLE showed that safinamide was safe and effective as adjunct therapy in patients with advanced Parkinson's disease (PD) and motor fluctuations. The addition of safinamide to a stable dose of levodopa alone or with other antiparkinsonian medications significantly increased ON time with no/non-troublesome dyskinesia, decreased OFF time and improved Parkinson's symptoms. OBJECTIVE: To evaluate the clinical effects of safinamide 100 mg/day on motor fluctuations and cardinal Parkinson's symptoms in specific patient subgroups using pooled data from Studies 016 and SETTLE. METHODS: Both studies were double blind, placebo-controlled, randomized, phase 3 trials which enrolled patients with mid- to late-stage PD experiencing motor fluctuations while receiving optimized and stable doses of levodopa, alone or with other dopaminergic treatments. The present post-hoc analyses assessed the change from baseline in ON time (with no or non-troublesome dyskinesia) and OFF time in subgroups of patients who were receiving only levodopa at baseline, who were classified as "mild fluctuators" (daily OFF time <=4 h), and who were receiving concomitant dopaminergic therapy, with or without amantadine, and the effects of safinamide versus placebo on individual cardinal PD symptoms during ON time. RESULTS: Safinamide significantly increased mean ON time (with no or non troublesome dyskinesia) and reduced mean OFF time when used as first adjunct therapy in levodopa-treated patients and patients with mild motor fluctuations. Mean daily ON time (with no or non-troublesome dyskinesia) and OFF time were favorably changed, compared with placebo, to similar extents regardless of whether patients were receiving concomitant dopamine agonists, catechol-O methyltransferase inhibitors and amantadine. Additionally, safinamide improved bradykinesia, rigidity, tremor and gait. CONCLUSIONS: Safinamide was a safe and effective first adjunct therapy in levodopa-treated patients and improved 4/5 cardinal symptoms of PD while providing benefits to mild and non-mild fluctuators and patients receiving other concomitant dopaminergic therapies. PMID- 26889633 TI - Improvement in Language Function Correlates with Gait Improvement in Drug-naive Parkinson's Disease Patients Taking Dopaminergic Medication. AB - BACKGROUND: Dopaminergic drugs, the gold standard for motor symptoms, are known to affect cognitive function in Parkinson's disease (PD) patients. OBJECTIVE: We compared the effects of dopaminergic treatment on motor and cognitive function in drug-naive patients. METHODS: Dopaminergic medication (levodopa, dopamine agonist, selegiline) was given to 27 drug-naive PD patients and increased to a dose optimal for improved motor symptoms. Patients were tested prior to, and 4-7 months after, drug initiation. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS). Cognitive function was assessed using both the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and the Neurobehavioral Cognitive Status Examination (COGNISTAT-J). Improvements from baseline for both motor and cognitive assessment were compared. RESULTS: Mean score of all motor assessments (UPDRS total score of Parts II and III, and sub scores of tremor, rigidity, bradykinesia, gait, and postural instability) and certain cognitive assessments (MoCA-J total score and subscore of delayed recall) significantly improved with dopaminergic medication. Gait score improvement showed significant positive correlation with improvement in MoCA-J language domain and in language-comprehension subtests of COGNISTAT-J using Spearman's correlation coefficients. Furthermore, multiple regression analysis showed gait score improvement significantly correlated with improvements in the subtests of language-comprehension in COGNISTAT-J. CONCLUSION: There is correlated improvement in both gait and language function in de novo PD patients in response to dopaminergic drugs. Gait and language dysfunction in these patients may share a common pathophysiology linked to dopamine deficits. PMID- 26889634 TI - Investigation of Genetic Variants Associated with Alzheimer Disease in Parkinson Disease Cognition. AB - BACKGROUND: Meta-analysis of genome-wide association studies have implicated multiple single nucleotide polymorphisms (SNPs) and associated genes with Alzheimer disease. The role of these SNPs in cognitive impairment in Parkinson disease (PD) remains incompletely evaluated. OBJECTIVE: The objective of this study was to test alleles associated with risk of Alzheimer disease for association with cognitive impairment in Parkinson disease (PD). METHODS: Two datasets with PD subjects accessed through the NIH database of Genotypes and Phenotypes contained both single nucleotide polymorphism (SNP) arrays and mini mental state exam (MMSE) scores. Genetic data underwent rigorous quality control and we selected SNPs for genes associated with AD other than APOE. We constructed logistic regression and ordinal regression models, adjusted for sex, age at MMSE, and duration of PD, to assess the association between selected SNPs and MMSE score. RESULTS: In one dataset, PICALM rs3851179 was associated with cognitive impairment (MMSE < 24) in PD subjects > 70 years old (OR = 2.3; adjusted p-value = 0.017; n = 250) but not in PD subjects <= 70 years old. CONCLUSIONS: Our finding suggests that PICALM rs3851179 could contribute to cognitive impairment in older patients with PD. It is important that future studies consider the interaction of age and genetic risk factors in the development of cognitive impairment in PD. PMID- 26889635 TI - Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder. AB - BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile. PMID- 26889636 TI - Lille Apathy Rating Scale and MDS-UPDRS for Screening Apathy in Parkinson's Disease. AB - BACKGROUND: Apathy is a syndrome characterized primarily by lack of motivation which may be associated with cognitive, affective and behavioral changes. Although the Lille Apathy Scale (LARS) has been extensively utilized in PD for detecting apathy and testing the effectiveness of specific therapeutic interventions, the highly variable cut-off values (between -11 and -22 points) ensures the applicability of the LARS degree of difficulty as a superb screening tool. OBJECTIVE: The aim of this study is to determine more reliable threshold values based on the neuropsychiatric status of patients. METHODS: Depression was assessed utilizing the Montgomery-Asberg Depression Rating Scale and neurocognitive status by Addenbrooke's Cognitive Examination. The presence of apathy was assessed by the proposed diagnostic criteria of Drijgers et al, and graded by both LARS and the 'Apathy' item of MDS-UPDRS. RESULTS: Based on multivariate regression analysis, we revealed the neurocognitive status, severity of depression, and also gender while applying dosage of dopamine agonists to determine the degree of patient apathy. Based on whether or not depression and neurocognitive disorders were indeed present, we established four different threshold values for the LARS: patients with normal cognition and without depression: -22.5; patients with normal cognition and with depression: -18.5; patients with NCD and without depression: -19.5; patients with NCD and with depression: -14.5. CONCLUSIONS: The LARS and the 'Apathy' item of MDS-UPDRS were confirmed to be potentially operational, beneficial and easy-to-assess instruments for detecting apathy syndrome in PD. However, there is no universal threshold value for the LARS suitable in all types of Parkinson's patients. PMID- 26889637 TI - Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson's Disease. AB - BACKGROUND: Parkinson's disease (PD) is a debilitating neurological disorder for which prognostic and diagnostic biomarkers are lacking. Cerebrospinal fluid (CSF) is an accessible body fluid that comes into direct contact with the central nervous system (CNS) and acts as a nuclease-free repository where RNA transcripts shed by brain tissues can reside for extended periods of time. OBJECTIVE: We studied the RNA species present in the CSF of PD patients to identify novel diagnostic biomarkers. METHODS: Small volumes of CSF from 27 PD patients and 30 healthy age- and sex-matched controls were used for RNA extraction followed by next-generation sequencing (RNA-seq) using the Illumina platform. CSF contains a number of fragmented RNA species that were individually sequenced and analyzed. Comparing PD to control subjects, we observed a pool of dysregulated sequencing tags that were further analyzed and validated by quantitative real-time PCR (qRT PCR). RESULTS: A total of 201 differentially expressed sequencing tags (DETs), including 92 up-regulated and 109 down-regulated DETs were identified. We validated the following DETs by real time PCR in the patient samples: Dnmt1, Ezh2, CCR3, SSTR5,PTPRC, UBC, NDUFV2, BMP7, SCN9, SCN9 antisense (AC010127.3), and long noncoding RNAs AC079630 and UC001lva.4 (close to the LRRK2 gene locus), as potential PD biomarkers. CONCLUSIONS: The CSF is a unique environment that contains many species of RNA. Our work demonstrates that CSF can potentially be used to identify biomarkers for the detection and tracking of disease progression and evaluation of therapeutic outcomes. PMID- 26889638 TI - Decoding Parkinson's Disease Pathogenesis: The Role of Deregulated mRNA Translation. AB - Mutations in a number of genes cause rare familial forms of Parkinson's disease and provide profound insight into potential mechanisms governing disease pathogenesis. Recently, a role for translation and metabolism of mRNA has emerged in the development of various neurodegenerative disorders including Parkinson's disease (PD). In PD, preliminary evidence supports a role for aberrant translation in the disease process stemming from mutations in several genes. Translation control is central to maintaining organism homeostasis under variable environmental conditions and deregulation of this may predispose to certain stressors. Hypothetically, deregulated translation may be detrimental to neuronal viability in PD through the misexpression of a subset of transcripts or through the impact of excessive bulk translation on energy consumption and burden on protein homeostatic mechanisms. While compelling preliminary evidence exists to support a role for translation in PD, much more work is required to identify specific mechanisms linking altered translation to the disease process. PMID- 26889641 TI - Photomultiplication photodetectors with P3HT:fullerene-free material as the active layers exhibiting a broad response. AB - A series of polymer photodetectors (PPDs) are fabricated based on P3HT as an electron donor and fullerene-free material DC-IDT2T as an electron acceptor. The only difference among these PPDs is the P3HT:DC-IDT2T doping weight ratios from 2 : 1 to 150 : 1. The PPDs with P3HT:DC-IDT2T (100 : 1, w/w) as the active layers exhibit champion external quantum efficiency (EQE) of 28 000% and 4000% corresponding to 390 nm and 750 nm light illumination at -20 V bias, respectively. The photomultiplication (PM) phenomenon should be attributed to the enhanced hole tunneling injection due to the interfacial band bending, which is induced by the trapped electrons in DC-IDT2T near the Al cathode. The high EQE value in the long wavelength range is due to the effect of DC-IDT2T photon harvesting and exciton dissociation on the interfacial trap-assisted hole tunneling injection. Meanwhile, the PPDs with DC-IDT2T as the electron acceptor exhibit superior stability compared with the PPDs with PC71BM as the electron acceptor. PMID- 26889639 TI - On the formulation of environmental fugacity models and their numerical solutions. AB - Multimedia models based on chemical fugacity, solved numerically, play an important role in investigating and quantifying the environmental fate of chemicals such as persistent organic pollutants. These models have been used extensively in studying the local and global distribution of chemicals in the environment. The present study describes potential sources of error that may arise from the formulation and numerical solution of environmental fugacity models. The authors derive a general fugacity equation for the rate of change of mass in an arbitrary volume (e.g., an environmental phase). Deriving this general equation makes clear several assumptions that are often not articulated but can be important for successfully applying multimedia fugacity models. It shows that the homogeneity of fugacity and fugacity capacity in a volume (the homogeneity assumption) is fundamental to formulating discretized fugacity models. It also shows that when using the fugacity rather than mass as the state-variable, correction terms may be necessary to accommodate environmental factors such as varying phase temperatures and volume. Neglecting these can lead to conservation errors. The authors illustrate the manifestation of these errors using heuristic multimedia fugacity models. The authors also show that there are easily avoided errors that can arise in mass state-variable models if variables are not updated appropriately in the numerical integration scheme. Environ Toxicol Chem 2016;35:2182-2191. (c) 2016 SETAC. PMID- 26889642 TI - Radiotherapy for persistent malignant transformation from mature cystic teratoma of the ovary. AB - Malignant transformations of mature cystic teratomas (MCT) are extremely rare and most of them are squamous cell carcinomas (SCC). Therefore no effective postoperative treatment has been established. In this article, we report two cases in which radiotherapy was effective for SCC arising from MCT. Case 1 was a 64-year-old woman with stage IIA of this tumor. After primary surgery, chemotherapy and interval debulking surgery were performed. She received radiotherapy for relapsed tumors, and has been well for 36 months since the initial diagnosis. Case 2 was a 37-year-old woman with stage IIB of this tumor. After primary debulking surgery, she received chemoradiotherapy for a residual tumor and has been well for 27 months since the surgery. Although there is no established therapy, radiotherapy or concurrent chemoradiotherapy might have beneficial effects on this tumor, similarly to those on SCC from other tissue. PMID- 26889643 TI - Three cases of symmetrical nevus of Ota and a brief literature review. PMID- 26889640 TI - Psychotropic use and associated neuropsychiatric symptoms among patients with dementia in the USA. AB - OBJECTIVE: To determine the national prevalence of psychotropic use and association with neuropsychiatric symptoms among patients with dementia. METHODS: Participants diagnosed with dementia (n = 414) in the Aging, Demographics, and Memory Study, a nationally representative survey of US adults >70 years old. Diagnosis was based on in-person clinical assessment and informant interview. Information collected included demographics, place of residence, 10-item Neuropsychiatric Inventory (NPI), and prescribed medications (antipsychotic, sedative-hypnotic, antidepressant, mood stabilizer). RESULTS: Of 414 participants with dementia, 41.4% were prescribed a psychotropic medication, including 84.0% of nursing home residents and 28.6% of community-dwellers. Of participants, 23.5% were prescribed an antidepressant. Compared with the total NPI score of those on no medication (4.5), those on antipsychotics and those on sedative-hypnotics had much higher scores (respectively: 12.6, p < 0.001; 11.8, p = 0.03), although those antidepressants did not (6.9, p = 0.15). A larger proportion of patients on antipsychotics exhibited psychosis and agitation compared with those on no medication, while those on antidepressants exhibited more depressive symptoms. In multivariable logistic regression that included dementia severity and nursing home residence, nursing home residence was the characteristic most strongly associated with psychotropic use (odds ratio ranging from 8.96 [p < 0.001] for antipsychotics to 15.59 [p < 0.001] for sedative-hypnotics). More intense psychotic symptoms and agitation were associated with antipsychotic use; more intense anxiety and agitation were associated with sedative-hypnotic use. More intense depression and apathy were not associated with antidepressant use. CONCLUSIONS: In this nationally representative sample, 41.4% of patients were taking psychotropic medication. While associated with neuropsychiatric symptoms, nursing home residence was most strongly tied to use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889645 TI - WiJ 2016 (March/April). PMID- 26889644 TI - Confirmed inguinal lymphogranuloma venereum genovar L2c in a man who had sex with men, Slovenia, 2015. AB - A laboratory-confirmed lymphogranuloma venereum (LGV) case in Slovenia was reported in 2015, in a human immunodeficiency virus (HIV)-negative man presenting with inguinal lymphadenopathy. He reported unprotected insertive anal intercourse with two male partners in Croatia. Variant L2c of Chlamydia trachomatis was detected in clinical samples. Although the patient was eventually cured, the recommended treatment regimen with doxycycline had to be prolonged. PMID- 26889646 TI - The 4S approach: a potential framework for supporting critical care nurses' patient assessment and interprofessional communication. PMID- 26889652 TI - A Strategy for Configuration of an Integrated Flexible Sulfur Cathode for High Performance Lithium-Sulfur Batteries. AB - Lithium-sulfur batteries are regarded as promising candidates for energy storage devices owing to their high theoretical energy density. The practical application is hindered, however, by low sulfur utilization and unsatisfactory capacity retention. Herein, we present a strategy for configuration of the sulfur cathode, which is composed of an integrated carbon/sulfur/carbon sandwich structure on polypropylene separator that is produced using the simple doctor-blade technique. The integrated electrode exhibits excellent flexibility and high mechanical strength. The upper and bottom carbon layers of the sandwich-structured electrode not only work as double current collectors, which effectively improve the conductivity of the electrode, but also serve as good barriers to suppress the diffusion of the polysulfide and buffer the volume expansion of the active materials, leading to suppression of the shuttle effect and low self-discharge behavior. PMID- 26889650 TI - A comparative study of rhodopsin function in the great bowerbird (Ptilonorhynchus nuchalis): Spectral tuning and light-activated kinetics. AB - Rhodopsin is the visual pigment responsible for initiating the phototransduction cascade in vertebrate rod photoreceptors. Although well-characterized in a few model systems, comparative studies of rhodopsin function, particularly for nonmammalian vertebrates are comparatively lacking. Bowerbirds are rare among passerines in possessing a key substitution, D83N, at a site that is otherwise highly conserved among G protein-coupled receptors. While this substitution is present in some dim-light adapted vertebrates, often accompanying another unusual substitution, A292S, its functional relevance in birds is uncertain. To investigate functional effects associated with these two substitutions, we use the rhodopsin gene from the great bowerbird (Ptilonorhynchus nuchalis) as a background for site-directed mutagenesis, in vitro expression and functional characterization. We also mutated these sites in two additional rhodopsins that do not naturally possess N83, chicken and bovine, for comparison. Both sites were found to contribute to spectral blue-shifts, but had opposing effects on kinetic rates. Substitutions at site 83 were found to primarily affect the kinetics of light-activated rhodopsin, while substitutions at site 292 had a larger impact on spectral tuning. The contribution of substitutions at site 83 to spectral tuning in particular depended on genetic background, but overall, the effects of substitutions were otherwise surprisingly additive, and the magnitudes of functional shifts were roughly similar across all three genetic backgrounds. By employing a comparative approach with multiple species, our study provides new insight into the joint impact of sites 83 and 292 on rhodopsin structure-function as well as their evolutionary significance for dim-light vision across vertebrates. PMID- 26889653 TI - Documentary analysis of risk-assessment and safety-planning policies and tools in a mental health context. AB - Despite the articulated need for policies and processes to guide risk assessment and safety planning, limited guidance exists on the processes or procedures to be used to develop such policies, and there is no body of research that examines the quality or content of the risk-management policies developed. The aim of the present study was to analyse the policies of risk and safety management used to guide mental health nursing practice in Ireland. A documentary analysis was performed on 123 documents received from 22 of the 23 directors of nursing contacted. Findings from the analysis revealed a wide variation in how risk, risk assessment, and risk management were defined. Emphasis within the risk documentation submitted was on risk related to self and others, with minimal attention paid to other types of risks. In addition, there was limited evidence of recovery-focused approaches to positive risk taking that involved service users and their families within the risk-related documentation. Many of the risk assessment tools had not been validated, and lacked consistency or guidance in relation to how they were to be used or applied. The tick-box approach and absence of space for commentary within documentation have the potential to impact severely on the quality of information collected and documented, and subsequent clinical decision-making. Managers, and those tasked with ensuring safety and quality, need to ensure that policies and processes are, where possible, informed by best evidence and are in line with national mental health policy on recovery. PMID- 26889654 TI - Does plant apparency matter? Thirty years of data provide limited support but reveal clear patterns of the effects of plant chemistry on herbivores. AB - According to the plant-apparency hypothesis, apparent plants allocate resources to quantitative defenses that negatively affect generalist and specialist herbivores, while unapparent plants invest more in qualitative defenses that negatively affect nonadapted generalists. Although this hypothesis has provided a useful framework for understanding the evolution of plant chemical defense, there are many inconsistencies surrounding associated predictions, and it has been heavily criticized and deemed obsolete. We used a hierarchical Bayesian meta analysis model to test whether defenses from apparent and unapparent plants differ in their effects on herbivores. We collected a total of 225 effect sizes from 158 published papers in which the effects of plant chemistry on herbivore performance were reported. As predicted by the plant-apparency hypothesis, we found a prevalence of quantitative defenses in woody plants and qualitative defenses in herbaceous plants. However, the detrimental impacts of qualitative defenses were more effective against specialists than generalists, and the effects of chemical defenses did not significantly differ between specialists and generalists for woody or herbaceous plants. A striking pattern that emerged from our data was a pervasiveness of beneficial effects of secondary metabolites on herbivore performance, especially generalists. This pattern provides evidence that herbivores are evolving effective counteradaptations to putative plant defenses. PMID- 26889651 TI - International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. AB - BACKGROUND: The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). METHODS: Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. RESULTS: The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. CONCLUSION: As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. PMID- 26889656 TI - The expression dynamics of mechanosensitive genes in extra-embryonic vasculature after heart starts to beat in chick embryo. AB - BACKGROUND: Fluid flow plays an important role in vascular development. However, the detailed mechanisms, particularly the link between flow and modulation of gene expression during vascular development, remain unexplored. In chick embryo, the key events of vascular development from initiation of heart beat to establishment of effective blood flow occur between the stages HH10 and HH13. Therefore, we propose a novel in vivo model to study the flow experienced by developing endothelium. OBJECTIVE: Using this model, we aimed to capture the transcriptome dynamics of the pre- and post-flow conditions. METHODS: RNA was isolated from extra embryonic area vasculosa (EE-AV) pooled from three chick embryos between HH10-HH13 and RNA sequencing was performed. RESULTS: The whole transcriptome sequencing of chick identified up-regulation of some of the previously well-known mechanosensitive genes including NFR2, HAND1, CTGF and KDR. GO analyses of the up-regulated genes revealed enrichment of several biological processes including heart development, extracellular matrix organization, cell matrix adhesion, cell migration, blood vessel development, patterning of blood vessels, collagen fibril organization. Genes encoding for gap junctions proteins which are involved in vascular remodeling and arterial-venous differentiation, and genes involved in cell-cell adhesion, and ECM interactions were significantly up-regulated. Validation of selected genes through semi quantitative PCR was performed. CONCLUSION: The study indicates that shear stress plays a major role in development. Through appropriate validation, this platform can serve as an in vivo model to study conditions of disturbed flow in pathology as well as normal flow during development. PMID- 26889655 TI - Protective effects of drag-reducing polymers in a rat model of monocrotaline induced pulmonary hypertension. AB - OBJECTIVES: Drag-reducing polymers (DRPs) are blood-soluble macromolecules which may increase blood flow and reduce vascular resistance. The purpose of the present study was to observe the effect of DRPs on monocrotaline-induced pulmonary hypertension (PH) in the rat model. METHODS: A total of 64 male Wistar rats were randomly divided into four groups: Group I (pulmonary hypertension model + DRP treatment); Group II (pulmonary hypertension model + saline treatment); Group III (control + DRP treatment); Group IV (control + saline treatment). After five weeks, comparisons were made of the following indices: survival rate, body weight, blood pressure, right ventricular systolic pressure, right ventricular hypertrophy, wall thickness of pulmonary arteries, the internal diameter of small pulmonary arteries, plasma IL-1beta and IL-6. RESULTS: The survival rate after 5 weeks varied significantly across all groups (P=0.013), but the survival rates of Groups I and II were not statistically significantly different. Administration of DRP (intravenous injection twice weekly) attenuated the PH-induced increase in right ventricular systolic pressure and suppressed the increases in right ventricular (RV) weight and the ratio of right ventricular weight to left ventricle plus septum weight (RV/LV + S). DRP treatment also significantly decreased the wall thickness of pulmonary arteries, augmented the internal diameter of small pulmonary arteries, and suppressed increases in the plasma levels of IL-1beta and IL-6. CONCLUSIONS: DRP treatment with intravenous injection effectively inhibited the development of monocrotaline-induced pulmonary hypertension in the rat model. DRPs may have potential application for the treatment of pulmonary hypertension. PMID- 26889657 TI - Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment. AB - Tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP) and tris(1 chloro-2-propyl) phosphate (TCIPP) are current high-volume organophosphate flame retardants/plasticizers (PFRs) and are abundant in the indoor environment. While recent in vitro research has indicated potential toxic effects in the endocrine system, biotransformation of these compounds is still underexplored. In this study, we aimed to characterize the metabolite formation for three PFRs in primary human hepatocytes, an in vitro system that mimics in vivo liver metabolism more closely than hepatic subcellular fractions or cell lines. Cryopreserved human hepatocytes were thawed and suspended in media with 50 MUm TBOEP or TCIPP, or 20 MUm TPHP up to 2 h. Extracts were analyzed by liquid chromatography-quadrupole-time-of-flight-mass spectrometry. Quantification of biotransformation products in hepatocytes exposed for 2 h revealed that bis(1 chloro-2-propyl) phosphate and diphenyl phosphate corresponded to less than half of the depletion of TCIPP and TPHP, respectively, while bis(2-butoxyethyl) 2 hydroxyethyl phosphate compared to 40-66% of the depletion of TBOEP. Other metabolite structures of these PFRs were produced at 4- to 10-fold lower rates. These findings help interpret biological levels of the major metabolites and relate it to levels of their parent PFR. Percentage of substrate depletion was largest for TBOEP followed by comparable values for TPHP and TCIPP, indicating that hepatic clearance of TPHP and TCIPP would be slower than that of TBOEP. The resulting higher levels and longer presence of TPHP in the circulation after exposure, would allow TPHP a larger time window to exert its suspected adverse effects compared to TBOEP. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889659 TI - Novel strategies for molecular targeting to cancer. AB - This editorial draws attention to the work published by CEPP in 2014-2015 on mechanisms underlying cancer drug resistance, invasion and metastasis. Genetic, genomic and immunological changes in platinum drug resistance and new drug candidates for cancer metastasis are highlighted. Attention is paid to the Epimedium plant drug icariin in glioblastoma invasion, the plant Avicennia marina bioactive compound Naphtho[1,2-b]furan-4,5-dione in breast cancer metastasis, the PI3K inhibitor BEZ235 in colon cancer stem cells, the histone methyltransferase EZH1 inhibitor GSK343 in cervical cancer, and vitamin D3 in prostate cancer. PMID- 26889658 TI - alpha-Ketobenzothiazole Serine Protease Inhibitors of Aberrant HGF/c-MET and MSP/RON Kinase Pathway Signaling in Cancer. AB - Upregulation of the HGF and MSP growth-factor processing serine endopeptidases HGFA, matriptase and hepsin is correlated with increased metastasis in multiple tumor types driven by c-MET or RON kinase signaling. We rationally designed P1' alpha-ketobenzothiazole mechanism-based inhibitors of these proteases. Structure activity studies are presented, which resulted in the identification of potent inhibitors with differential selectivity. The tetrapeptide inhibitors span the P1 P1' substrate cleavage site via a P1' amide linker off the benzothiazole, occupying the S3' pocket. Optimized inhibitors display sub-nanomolar enzyme inhibition against one, two, or all three of HGFA, matriptase, and hepsin. Several compounds also have good selectivity against the related trypsin-like proteases, thrombin and Factor Xa. Finally, we show that inhibitors block the fibroblast (HGF)-mediated migration of invasive DU145 prostate cancer cells. In addition to prostate cancer, breast, colon, lung, pancreas, gliomas, and multiple myeloma tumors all depend on HGF and MSP for tumor survival and progression. Therefore, these unique inhibitors have potential as new therapeutics for a diverse set of tumor types. PMID- 26889660 TI - Renal risk-benefit determinants of recombinant human erythropoietin therapy in the remnant kidney rat model - hypertension, anaemia, inflammation and drug dose. AB - Clinical studies showed that high doses of recombinant human erythropoietin (rHuEPO) used to correct anaemia in chronic kidney disease (CKD) hyporesponsive patients may lead to deleterious effects. The aim of this study was to analyze the effects of rHuEPO in doses usually used to correct CKD-anaemia (100, 200 IU/kg body weight (BW) per week) and in higher doses used in the treatment of hyporesponsive patients (400, 600 IU/kg BW per week), focusing on renal damage, hypoxia, inflammation and fibrosis. Male Wistar rats with chronic renal failure (CRF) induced by 5/6 nephrectomy were treated with rHuEPO or with vehicle, over a 3-week period. Haematological, biochemical and renal function analyses were performed. Kidney and liver mRNA levels were evaluated by quantitative real-time polymerase chain reaction (qPCR) and protein expression by Western blot and immunohistochemistry. Kidney histopathological evaluations were also performed. The CRF group developed anaemia, hypertension and a high score of renal histopathologic lesions. Correction of anaemia was achieved with all rHuEPO doses, with improvement in hypertension, renal function and renal lesions. In addition, the higher rHuEPO doses also improved inflammation. Blood pressure was reduced in all rHuEPO-treated groups, compared to the CRF group, but increased in a dose-dependent manner. The current study showed that rHuEPO treatment corrected anaemia and improved urinary albumin excretion, particularly at lower doses. In addition, it is suggested that a short-term treatment with high doses, used to overcome an episode of hyporesponsiveness to rHuEPO therapy, can present benefits by reducing inflammation, without worsening of renal lesions; however, the pro hypertensive effect should be considered, and carefully managed to avoid a negative cardiorenal impact. PMID- 26889661 TI - Intercellular Connections Related to Cell-Cell Crosstalk Specifically Recognized by an Aptamer. AB - Intercellular connections are an important pathway for cell-cell crosstalk. However, their formation mechanism and functions are far from being understood. The lack of molecular probes hampers the research in this area. Herein, we report a kind of intercellular connection that is specifically recognized by aptamer M17A2 generated by cell-SELEX against MCF-7R cells. These connections have different morphologies, but have the same skeleton composed of F-actin. The long filamentous connections were identified to be tunneling nanotubes (TNTs), a recently discovered cell-cell communication route. These connections could be built not only between MCF-7R cells, but also from MCF-7R to other cells after co culture. Proteins could be transported between cells through these connections, suggesting their cell communication function. Aptamer M17A2 shows the potential to act as a new probe for investigating this kind of intercellular connection, as well as for studying cell-cell communication. PMID- 26889662 TI - Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know. AB - Zika virus is a flavivirus transmitted by Aedes (Stegomyia) species of mosquitoes. In May 2015, the World Health Organization confirmed the first local transmission of Zika virus in the Americas in Brazil. The virus has spread rapidly to other countries in the Americas; as of January 29, 2016, local transmission has been detected in at least 22 countries or territories, including the Commonwealth of Puerto Rico and the U.S. Virgin Islands. Zika virus can infect pregnant women in all three trimesters. Although pregnant women do not appear to be more susceptible to or more severely affected by Zika virus infection, maternal-fetal transmission has been documented. Several pieces of evidence suggest that maternal Zika virus infection is associated with adverse neonatal outcomes, most notably microcephaly. Because of the number of countries and territories with local Zika virus transmission, it is likely that obstetric health care providers will care for pregnant women who live in or have traveled to an area of local Zika virus transmission. We review information on Zika virus, its clinical presentation, modes of transmission, laboratory testing, effects during pregnancy, and methods of prevention to assist obstetric health care providers in caring for pregnant women considering travel or with a history of travel to areas with ongoing Zika virus transmission and pregnant women residing in areas with ongoing Zika virus transmission. PMID- 26889664 TI - Assessment of short-term variability in human spontaneous blink rate during video observation with or without head / chin support. AB - BACKGROUND: The aim was to assess the variability of spontaneous blink rate (SBR) with and without a chin and forehead support. METHODS: Forty-eight healthy non contact lens wearers, aged from 20 to 39 years, had five-minute video recordings made under ambient lighting of 350 to 400 lux, while directing their gaze to a distant target at head height. Half the subjects (group 1) were seated resting against the chair head rest and the other half (group 2) seated but with chin and forehead at a slitlamp. The first 35 blinks were analysed in detail. RESULTS: As assessed over five minutes, 35 to 111 blinks were counted, with SBR between 6.9 and 21.8 blinks per min (average 13.9 per min). Over the initial 35 blinks, the average momentary SBR values (calculated from the inter-blink intervals) averaged 24.8 blinks per minute in group 1 and 19.3 blinks per minute in group 2 (not significantly different, p = 0.273) but a statistically significant (p < 0.001) decrease in SBR was observed over the initial 10 to 15 blinks in group 2. The variability in momentary SBR values, as assessed from successive blinks, had coefficient of variation (COV) values of 80 and 78 per cent, respectively over 35 blinks. CONCLUSIONS: Averaged spontaneous blink rates over short time periods (that is, five minutes) should be suitable to compare various experimental paradigms but if very short periods are used (for example one minute or less), then there could be significant time-related changes, especially when a subject is seated with chin and forehead support. PMID- 26889663 TI - Far-Field Spectroscopy and Near-Field Optical Imaging of Coupled Plasmon-Phonon Polaritons in 2D van der Waals Heterostructures. AB - A new hybridized plasmon-phonon polariton mode in graphene/h-BN van der Waals heterostructures is presented, featuring the ultrahigh field confinement characteristic of the graphene plasmon and the long lifetime property of the h-BN transverse optical phonon. This enables an ultralong hybrid plasmon lifetime of up to 1.6 ps (with ultrahigh mode confinement up to >l0(2)/7000 and ultrasmall group velocity down to 0.001c, where c is the speed of light in vacuum), superior to any localized plasmon ever demonstrated. PMID- 26889665 TI - Preparation of Monodomain Liquid Crystal Elastomers and Liquid Crystal Elastomer Nanocomposites. AB - LCEs are shape-responsive materials with fully reversible shape change and potential applications in medicine, tissue engineering, artificial muscles, and as soft robots. Here, we demonstrate the preparation of shape-responsive liquid crystal elastomers (LCEs) and LCE nanocomposites along with characterization of their shape-responsiveness, mechanical properties, and microstructure. Two types of LCEs - polysiloxane-based and epoxy-based - are synthesized, aligned, and characterized. Polysiloxane-based LCEs are prepared through two crosslinking steps, the second under an applied load, resulting in monodomain LCEs. Polysiloxane LCE nanocomposites are prepared through the addition of conductive carbon black nanoparticles, both throughout the bulk of the LCE and to the LCE surface. Epoxy-based LCEs are prepared through a reversible esterification reaction. Epoxy-based LCEs are aligned through the application of a uniaxial load at elevated (160 degrees C) temperatures. Aligned LCEs and LCE nanocomposites are characterized with respect to reversible strain, mechanical stiffness, and liquid crystal ordering using a combination of imaging, two-dimensional X-ray diffraction measurements, differential scanning calorimetry, and dynamic mechanical analysis. LCEs and LCE nanocomposites can be stimulated with heat and/or electrical potential to controllably generate strains in cell culture media, and we demonstrate the application of LCEs as shape-responsive substrates for cell culture using a custom-made apparatus. PMID- 26889667 TI - Isolation of microsatellite loci and reliable genotyping using noninvasive samples of a critically endangered primate, Trachypithecus leucocephalus. AB - Genetic information can be critical in identifying conservation priorities and developing conservation strategies. There is an urgent need for noninvasive genetic tools to study the wild populations of Asian colobine monkeys. The majority of these species are threatened with habitat destruction, population reduction and even extinction, but generally lack information on their genetic diversity and population structure. Genetic sampling and tissue collection have been scarce in these species owing to strict regulations on manipulation of endangered species, and the difficulties and risks associated with capturing these arboreal and fast-moving monkeys in the challenging environments that they inhabit. These difficulties have hindered the development of molecular genetic markers, which are usually derived from tissues or blood. In this study, we present a method for de novo microsatellite isolation and genotyping using DNA from noninvasive origins of a critically endangered Asian colobine, the white headed langur (Trachypithecus leucocephalus). Genomic DNA isolated from hair was shown to be sufficient for microsatellite enrichment and isolation, with similar isolation efficiencies as from tissue DNA. We identified and characterized 20 polymorphic microsatellite loci, and evaluated their amplification success and genotyping reliability with 86 field-collected fecal samples. These results show that this panel of loci can produce reliable genotypes from fecal samples, and represent a useful tool for noninvasive investigation of genetic structure, individual identification and kinship assessment in this highly endangered species. Our approach can be applied to conservation genetic studies of other wild species that lack sequence information and tissue samples. PMID- 26889669 TI - Debate surrounds state laws for Down syndrome fact sheets: Controversy revolves around whether states are attempting to intrude too much in the communication between patients and providers. PMID- 26889666 TI - Concise Review: Control of Cell Fate Through Cell Cycle and Pluripotency Networks. AB - Pluripotent stem cells (PSCs) proliferate rapidly with a characteristic cell cycle structure consisting of short G1- and G2-gap phases. This applies broadly to PSCs of peri-implantation stage embryos, cultures of embryonic stem cells, induced pluripotent stem cells, and embryonal carcinoma cells. During the early stages of PSC differentiation however, cell division times increase as a consequence of cell cycle remodeling. Most notably, this is indicated by elongation of the G1-phase. Observations linking changes in the cell cycle with exit from pluripotency have raised questions about the role of cell cycle control in maintenance of the pluripotent state. Until recently however, this has been a difficult question to address because of limitations associated with experimental tools. Recent studies now show that pluripotency and cell cycle regulatory networks are intertwined and that cell cycle control mechanisms are an integral, mechanistic part of the PSC state. Studies in embryonal carcinoma, some 30 years ago, first suggested that pluripotent cells initiate differentiation when in the G1-phase. More recently, a molecular "priming" mechanism has been proposed to explain these observations in human embryonic stem cells. Complexity in this area has been increased by the realization that pluripotent cells exist in multiple developmental states and that in addition to each having their own characteristic gene expression and epigenetic signatures, they potentially have alternate modes of cell cycle regulation. This review will summarize current knowledge in these areas and will highlight important aspects of interconnections between the cell cycle, self-renewal, pluripotency, and cell fate decisions. Stem Cells 2016;34:1427-1436. PMID- 26889670 TI - Noninvasive prenatal testing can detect gene deletions, duplications: Use of cell free fetal DNA for NIPT promising but not yet ready for clinical use. PMID- 26889668 TI - Selective association of electrocardiographic abnormalities with insulin sensitivity and beta-cell function in type 2 diabetes mellitus: a cross-sectional analysis. AB - BACKGROUND: We investigated the association of electrocardiographic (ECG) abnormalities with markers of insulin resistance and pancreatic beta-cell dysfunction in a cross-sectional study of type 2 diabetes patients. METHODS: Electrocardiographic criteria were evaluated in the Penn Diabetes Heart Study participants (n = 1671; 64% male; 61% Caucasian), including a sub-sample (n = 710) that underwent oral glucose tolerance testing. The Matsuda Insulin Sensitivity Index and homeostasis model assessment of insulin resistance (HOMA IR) estimated insulin sensitivity; Insulinogenic Index and homeostasis model assessment of beta-cell function assessed beta-cell function. Multivariable regression modelling was used to analyse associations of ECG changes with these indices. RESULTS: In unadjusted analyses, subjects in the highest quartile of Matsuda index had the lowest prevalence of Q-waves (6.3% versus 15.3%, p = 0.005). In adjusted models, an inverse association was seen between Q-waves and log Matsuda index [one standard deviation increase; OR = 0.59 (95% CI 0.43-0.87 p = 0.001)]. In the full Penn Diabetes Heart Study, there was a direct association between Q-waves and HOMA-IR [one standard deviation increase; OR = 1.43 (95% CI 1.13-1.81, p = 0.003)]. In adjusted models, left ventricular hypertrophy also was inversely associated with Matsuda index and directly with HOMA-IR. Higher Insulinogenic Index scores were associated with a lower prevalence of nonspecific ST changes [OR = 0.78 (95% CI 0.62-0.98, p = 0.032)]. CONCLUSIONS: In type 2 diabetic patients, both oral glucose tolerance testing-derived and HOMA-derived measures of insulin resistance were associated with pathologic Q-waves and left ventricular hypertrophy on ECGs. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889671 TI - Noninvasive prenatal testing spots Duchenne muscular dystrophy. PMID- 26889674 TI - Combining QMRA and Epidemiology to Estimate Campylobacteriosis Incidence. AB - The disease burden of pathogens as estimated by QMRA (quantitative microbial risk assessment) and EA (epidemiological analysis) often differs considerably. This is an unsatisfactory situation for policymakers and scientists. We explored methods to obtain a unified estimate using campylobacteriosis in the Netherlands as an example, where previous work resulted in estimates of 4.9 million (QMRA) and 90,600 (EA) cases per year. Using the maximum likelihood approach and considering EA the gold standard, the QMRA model could produce the original EA estimate by adjusting mainly the dose-infection relationship. Considering QMRA the gold standard, the EA model could produce the original QMRA estimate by adjusting mainly the probability that a gastroenteritis case is caused by Campylobacter. A joint analysis of QMRA and EA data and models assuming identical outcomes, using a frequentist or Bayesian approach (using vague priors), resulted in estimates of 102,000 or 123,000 campylobacteriosis cases per year, respectively. These were close to the original EA estimate, and this will be related to the dissimilarity in data availability. The Bayesian approach further showed that attenuating the condition of equal outcomes immediately resulted in very different estimates of the number of campylobacteriosis cases per year and that using more informative priors had little effect on the results. In conclusion, EA was dominant in estimating the burden of campylobacteriosis in the Netherlands. However, it must be noted that only statistical uncertainties were taken into account here. Taking all, usually difficult to quantify, uncertainties into account might lead to a different conclusion. PMID- 26889673 TI - Generating a taxonomy for genetic conditions relevant to reproductive planning. AB - As genome or exome sequencing (hereafter genome-scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome-scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be complicated. Carrier testing generally occurs in the context of reproductive decision-making and involves patient values in a way that other types of genetic testing may not. The Kaiser Permanente Clinical Sequencing Exploratory Research program is conducting a randomized clinical trial of preconception carrier testing that allows participants to select their preferences for results from among broad descriptive categories rather than selecting individual conditions. This paper describes (1) the criteria developed by the research team, the return of results committee (RORC), and stakeholders for defining the categories; (2) the process of refining the categories based on input from patient focus groups and validation through a patient survey; and (3) how the RORC then assigned specific gene-condition pairs to taxonomy categories being piloted in the trial. The development of four categories (serious, moderate/mild, unpredictable, late onset) for sharing results allows patients to select results based on their values without separately deciding their interest in knowing their carrier status for hundreds of conditions. A fifth category, lifespan limiting, was always shared. The lessons learned may be applicable in other results disclosure situations, such as incidental findings. PMID- 26889675 TI - The Interplay between Myc and CTP Synthase in Drosophila. AB - CTP synthase (CTPsyn) is essential for the biosynthesis of pyrimidine nucleotides. It has been shown that CTPsyn is incorporated into a novel cytoplasmic structure which has been termed the cytoophidium. Here, we report that Myc regulates cytoophidium formation during Drosophila oogenesis. We have found that Myc protein levels correlate with cytoophidium abundance in follicle epithelia. Reducing Myc levels results in cytoophidium loss and small nuclear size in follicle cells, while overexpression of Myc increases the length of cytoophidia and the nuclear size of follicle cells. Ectopic expression of Myc induces cytoophidium formation in late stage follicle cells. Furthermore, knock down of CTPsyn is sufficient to suppress the overgrowth phenotype induced by Myc overexpression, suggesting CTPsyn acts downstream of Myc and is required for Myc mediated cell size control. Taken together, our data suggest a functional link between Myc, a renowned oncogene, and the essential nucleotide biosynthetic enzyme CTPsyn. PMID- 26889676 TI - The Responses of Medical General Practitioners to Unreasonable Patient Demand for Antibiotics--A Study of Medical Ethics Using Immersive Virtual Reality. AB - BACKGROUND: Dealing with insistent patient demand for antibiotics is an all too common part of a General Practitioner's daily routine. This study explores the extent to which portable Immersive Virtual Reality technology can help us gain an accurate understanding of the factors that influence a doctor's response to the ethical challenge underlying such tenacious requests for antibiotics (given the threat posed by growing anti-bacterial resistance worldwide). It also considers the potential of such technology to train doctors to face such dilemmas. EXPERIMENT: Twelve experienced GPs and nine trainees were confronted with an increasingly angry demand by a woman to prescribe antibiotics to her mother in the face of inconclusive evidence that such antibiotic prescription is necessary. The daughter and mother were virtual characters displayed in immersive virtual reality. The specific purposes of the study were twofold: first, whether experienced GPs would be more resistant to patient demands than the trainees, and second, to investigate whether medical doctors would take the virtual situation seriously. RESULTS: Eight out of the 9 trainees prescribed the antibiotics, whereas 7 out of the 12 GPs did so. On the basis of a Bayesian analysis, these results yield reasonable statistical evidence in favor of the notion that experienced GPs are more likely to withstand the pressure to prescribe antibiotics than trainee doctors, thus answering our first question positively. As for the second question, a post experience questionnaire assessing the participants' level of presence (together with participants' feedback and body language) suggested that overall participants did tend towards the illusion of being in the consultation room depicted in the virtual reality and that the virtual consultation taking place was really happening. PMID- 26889677 TI - Surveillance of the Sensitivity towards Antiparasitic Bath-Treatments in the Salmon Louse (Lepeophtheirus salmonis). AB - The evolution of drug resistant parasitic sea lice is of major concern to the salmon farming industry worldwide and challenges sustainable growth of this enterprise. To assess current status and development of L. salmonis sensitivity towards different pesticides used for parasite control in Norwegian salmon farming, a national surveillance programme was implemented in 2013. The programme aims to summarize data on the use of different pesticides applied to control L. salmonis and to test L. salmonis sensitivity to different pesticides in farms along the Norwegian coast. Here we analyse two years of test-data from biological assays designed to detect sensitivity-levels towards the pesticides azamethiphos and deltamethrin, both among the most common pesticides used in bath-treatments of farmed salmon in Norway in later years. The focus of the analysis is on how different variables predict the binomial outcome of the bioassay tests, being whether L. salmonis are immobilized/die or survive pesticide exposure. We found that local kernel densities of bath treatments, along with a spatial geographic index of test-farm locations, were significant predictors of the binomial outcome of the tests. Furthermore, the probability of L. salmonis being immobilized/dead after test-exposure was reduced by odds-ratios of 0.60 (95% CI: 0.42-0.86) for 2014 compared to 2013 and 0.39 (95% CI: 0.36-0.42) for low concentration compared to high concentration exposure. There were also significant but more marginal effects of parasite gender and developmental stage, and a relatively large random effect of test-farm. We conclude that the present data support an association between local intensities of bath treatments along the coast and the outcome of bioassay tests where salmon lice are exposed to azamethiphos or deltamethrin. Furthermore, there is a predictable structure of L. salmonis phenotypes along the coast in the data, characterized by high susceptibility to pesticides in the far north and far south, but low susceptibility in mid Norway. The study emphasizes the need to address local susceptibility to pesticides and the need for restrictive use of pesticides to preserve treatment efficacy. PMID- 26889678 TI - The ABC of Hidradenitis Suppurativa: A Validated Glossary on how to Name Lesions. AB - BACKGROUND: The precise clinical description of skin lesions observed in some patients with hidradenitis suppurativa (HS) can be extremely difficult. OBJECTIVE: Establishing a validated glossary of terms allowing the best possible description of lesions observed in HS patients. MATERIAL AND METHODS: Five international experts of HS were to assess a series of 25 photos representing typical lesions of this disorder. For each photo, the experts were asked whether naming of the lesions was possible or not and, if yes, by using which noun. Agreement of their responses was calculated using Fleiss's kappa index. Using a Delphi strategy, photos with disagreement were discussed, and photos were reevaluated on the next day. In case of agreement on the impossibility of naming some clinical situations, new terms, to be included into the glossary, were agreed upon. RESULTS: After the first round of photos, agreement between the experts was poor with a kappa index of only 0.33 (95% CI 0.22-0.46). After extensive discussion of cases with disagreement, the kappa index increased on day 2 to 0.75 (95% CI 0.60-0.87), allowing to conclude on good interobserver agreement on terminology. Furthermore, a few clinical situations were identified in which naming with established semantics is so far not possible. For these situations, the terms 'multicord', 'multipore', 'multitunnel' and 'retraction' were defined. DISCUSSION: This is the first validation of clinical terms used to describe lesions in patients with HS. This should be helpful in better defining the clinical phenotypes observed in this disorder. PMID- 26889679 TI - The Trypanosome Nuclear Pore Reveals 1.5 Billion Years of Similarities and Differences. PMID- 26889681 TI - Concepts of Chronic Lymphocytic Leukemia Pathogenesis: DNA Damage Response and Tumor Microenvironment. AB - Pathogenesis of chronic lymphocytic leukemia (CLL) is characterized by specific genetic aberrations and alterations of cellular signaling pathways. In particular, a disturbed DNA damage response (DDR) and an activated B-cell receptor signaling pathway play a major role in promoting CLL cell survival. External stimuli are similarly essential for CLL cell survival and lead to activation of the PI3K/AKT and MAPK pathways. Activation of nuclear factor-kappa B (NFkB) influences the disturbed anti-apoptotic balance of CLL cells. Losses or disabling mutations in TP53 and ATM are frequent events in chemotherapy-naive patients and are further enriched in chemotherapy-resistant patients. As these lesions define key regulatory elements of the DDR pathway, they also determine treatment response to genotoxic therapy. Novel therapeutic strategies therefore try to circumvent defective DDR signaling and to suppress the pro-survival stimuli received from the tumor microenvironment. With increasing knowledge on specific genetic alterations of CLL, we may be able to target CLL cells more efficiently even in the situation of mutated DDR pathways or protection by microenvironmental stimuli. PMID- 26889680 TI - Analytical Performance of ELISA Assays in Urine: One More Bottleneck towards Biomarker Validation and Clinical Implementation. AB - ELISA is the main approach for the sensitive quantification of protein biomarkers in body fluids and is currently employed in clinical laboratories for the measurement of clinical markers. As such, it also constitutes the main methodological approach for biomarker validation and further qualification. For the latter, specific assay performance requirements have to be met, as described in respective guidelines of regulatory agencies. Even though many clinical ELISA assays in serum are regularly used, ELISA clinical applications in urine are significantly less. The scope of our study was to evaluate ELISA assay analytical performance in urine for a series of potential biomarkers for bladder cancer, as a first step towards their large scale clinical validation. Seven biomarkers (Secreted protein acidic and rich in cysteine, Survivin, Slit homolog 2 protein, NRC-Interacting Factor 1, Histone 2B, Proteinase-3 and Profilin-1) previously described in the literature as having differential expression in bladder cancer were included in the study. A total of 11 commercially available ELISA tests for these markers were tested by standard curve analysis, assay reproducibility, linearity and spiking experiments. The results show disappointing performance with coefficients of variation>20% for the vast majority of the tests performed. Only 3 assays (for Secreted protein acidic and rich in cysteine, Survivin and Slit homolog 2 protein) passed the accuracy thresholds and were found suitable for further application in marker quantification. These results collectively reflect the difficulties in developing urine-based ELISA assays of sufficient analytical performance for clinical application, presumably attributed to the urine matrix itself and/or presence of markers in various isoforms. PMID- 26889682 TI - Malignant Potential of Gastrointestinal Cancers Assessed by Structural Equation Modeling. AB - BACKGROUND: Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling. MATERIALS AND METHODS: We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis. RESULTS: Because latent variables were disparate except for their number, 'three' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others. CONCLUSION: These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers. PMID- 26889684 TI - Mentally simulating narrative perspective is not universal or necessary for language comprehension. AB - Readers differentially adopt an agent's perspective as a function of pronouns encountered during reading. The present study assessed the reliability of this effect across narrative contexts and self-reported variation in levels of engagement during reading. Experiment 1 used an extended sample (N = 263) and replicated an interactive influence of pronouns on perspectives adopted during reading simple action sentences (e.g., You are peeling the cucumber.), with You promoting an agent's perspective, and He promoting an onlooker's external perspective. The magnitude of this effect was partially accounted for by individual differences in the tendency to get actively engaged during reading. Specifically, readers who self-reported greater empathic engagement during reading also showed a higher likelihood to adopt an agent's perspective when sentences used the pronoun You or I. Experiment 2 (N = 217) examined whether these influences of pronouns and individual differences would emerge with relatively realistic, extended narratives; effects were generally less robust than with single sentence scenarios, though empathic engagement still predicted adopting an agent's perspective with the pronoun You or I. Furthermore, even in the absence of perspective modulation in response to pronouns, comprehension was maintained. These results demonstrate that differentially adopting perspectives as a function of pronouns is not universal or necessary for comprehension, but rather influenced by narrative context and individuals' propensity to find themselves immersed in described events. Results are considered within the framework of embodied cognition, representational pluralism, individual differences, and high-powered replication projects. (PsycINFO Database Record PMID- 26889683 TI - Beyond Knowledge and Awareness: Addressing Misconceptions in Ghana's Preparation towards an Outbreak of Ebola Virus Disease. AB - BACKGROUND: Ebola Virus Disease (EVD) is not new to the world. However, the West African EVD epidemic which started in 2014 evolved into the largest, most severe and most complex outbreak in the history of the disease. The three most-affected countries faced enormous challenges in stopping the transmission and providing care for all patients. Although Ghana had not recorded any confirmed Ebola case, social factors have been reported to hinder efforts to control the outbreak in the three most affected countries. This qualitative study was designed to explore community knowledge and attitudes about Ebola and its transmission. METHODS: This study was carried out in five of the ten regions in Ghana. Twenty-five focus group discussions (N = 235) and 40 in-depth interviews were conducted across the five regions with community members, stakeholders and opinion leaders. The interviews were recorded digitally and transcribed verbatim. Framework analysis was adopted in the analysis of the data using Nvivo 10. RESULTS: The results showed a high level of awareness and knowledge about Ebola. The study further showed that knowledge on how to identify suspected cases of Ebola was also high among respondents. However, there was a firm belief that Ebola was a spiritual condition and could also be transmitted through air, mosquito bites and houseflies. These misconceptions resulted in perceptions of stigma and discrimination towards people who may get Ebola or work with Ebola patients. CONCLUSION: We conclude that although knowledge and awareness about Ebola is high among Ghanaians who participated in the study, there are still misconceptions about the disease. The study recommends that health education on Ebola disease should move beyond creating awareness to targeting the identified misconceptions to improve future containment efforts. PMID- 26889685 TI - Logic brightens my day: Evidence for implicit sensitivity to logical validity. AB - A key assumption of dual process theory is that reasoning is an explicit, effortful, deliberative process. The present study offers evidence for an implicit, possibly intuitive component of reasoning. Participants were shown sentences embedded in logically valid or invalid arguments. Participants were not asked to reason but instead rated the sentences for liking (Experiment 1) and physical brightness (Experiments 2-3). Sentences that followed logically from preceding sentences were judged to be more likable and brighter. Two other factors thought to be linked to implicit processing-sentence believability and facial expression-had similar effects on liking and brightness ratings. The authors conclude that sensitivity to logical structure was implicit, occurring potentially automatically and outside of awareness. They discuss the results within a fluency misattribution framework and make reference to the literature on discourse comprehension. (PsycINFO Database Record PMID- 26889686 TI - Effects of morphology and semantic transparency on typing latencies in english compound and pseudocompound words. AB - We used a typing task to measure the written production of compounds, pseudocompounds, and monomorphemic words on a letter-by-letter basis to determine whether written production (as measured by interletter typing speed) was affected by morphemic structure and semantic transparency of the constituents. Semantic transparency was analyzed using a dichotomous classification (opaque vs. transparent) as well as participant ratings. Our results indicate that written production is sensitive to morphemic structure and to the semantic transparency of the first constituent. (PsycINFO Database Record PMID- 26889688 TI - Mass Spectrometry in Plant-omics. AB - Plant-omics is rapidly becoming an important field of study in the scientific community due to the urgent need to address many of the most important questions facing humanity today with regard to agriculture, medicine, biofuels, environmental decontamination, ecological sustainability, etc. High-performance mass spectrometry is a dominant tool for interrogating the metabolomes, peptidomes, and proteomes of a diversity of plant species under various conditions, revealing key insights into the functions and mechanisms of plant biochemistry. PMID- 26889689 TI - Flexible resistive switching memory with a Ni/CuO x /Ni structure using an electrochemical deposition process. AB - Flexible resistive switching memory (ReRAM) devices were fabricated with a Ni/CuO x /Ni structure. Fabrication involved simple and low-cost electrochemical deposition of electrodes and resistive switching layers on a polyethylene terephthalate substrate. The devices exhibited reproducible and reliable ReRAM characteristics. Bipolar resistive switching was observed in flexible Ni/CuO x /Ni-based ReRAM devices with low operation voltages. The reliability of the devices was confirmed by data retention, endurance, and cyclic bending measurements. The processes for fabrication of flexible ReRAM devices were based on simple-solution, bottom-up growth and they can be performed at low temperatures. Therefore, the methods presented in this work could be a viable solution for fabricating flexible non-volatile memory devices in the future. PMID- 26889687 TI - Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function. AB - Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects. PMID- 26889690 TI - Development of cycling skills in 7- to 12-year-old children. AB - OBJECTIVE: Cycling is a complex skill consisting of motor skills such as pedalling, braking, and steering. Because the ability to perform cycling skills is based on the age-related development of the child, experience and age-related reference values are of interest in light of customized testing and training. METHODS: One hundred thirty-eight children from the second (7-8 years), fourth (9 10 years), and sixth (11-12 years) grades performed a practical bicycle test consisting of 13 test items with specific points of interest. Moreover, age at onset of cycling, cycling to and from school, independent mobility, and minutes cycling per week were estimated using a parental questionnaire. RESULTS: It is found that cycling skills are strongly related to age with 11- to 12-year-old children outperforming 7- to 8-year-old children for 11 test items and 9- to 10 year-old children for 8 test items. CONCLUSIONS: Next to age, age at onset of cycling also contributed to cycling skills. Therefore, our results suggest that cycling skills are associated with physical and mental maturation. Subsequently, age-related reference values are provided to customize testing and training. PMID- 26889691 TI - Short-term balance training with computer-based feedback in children with cerebral palsy: A feasibility and pilot randomized trial. AB - OBJECTIVE: To assess the feasibility of using short-term balance training with computer-based visual feedback (BTVF) and its effect on standing balance in children with bilateral spastic cerebral palsy (BSCP). METHODS: Out of the fourteen children with BSCP (mean age = 10.31 years), seven children received four sessions of BTVF (two such sessions/day, each session = 15 min) in comparison to the control group that received standard care. Feasibility was measured as percentages of recruitment, retention and safety and balance was measured using a posturography machine as sway velocity (m/s) and velocity moment (m/s2) during quiet standing. RESULTS: No serious adverse events occurred in either group. There were no differences in the retention percentages and in any clinical outcome measure between both groups. CONCLUSION: Use of BTVF is feasible in children with BSCP but further investigation is required to estimate a dose effect relationship. PMID- 26889693 TI - Pan-proteomics, a concept for unifying quantitative proteome measurements when comparing closely-related bacterial strains. AB - The comparison of proteomes between genetically heterogeneous bacterial strains may offer valuable insights into physiological diversity and function, particularly where such variation aids in the survival and virulence of clinically-relevant strains. However, reports of such comparisons frequently fail to account for underlying genetic variance. As a consequence, the current knowledge regarding bacterial physiological diversity at the protein level may be incomplete or inaccurate. To address this, greater consideration must be given to the impact of genetic heterogeneity on proteome comparisons. This may be possible through the use of pan-proteomics, an analytical concept that permits the ability to qualitatively and quantitatively compare the proteomes of genetically heterogeneous organisms. Limited examples of this emerging technology highlight currently unmet analytical challenges. In this article we define pan-proteomics, where its value lies in microbiology, and discuss the technical considerations critical to its successful execution and potential future application. PMID- 26889692 TI - Hexavalent chromium removal and bioelectricity generation by Ochrobactrum sp. YC211 under different oxygen conditions. AB - Bioremediation is an environmentally friendly method of reducing heavy metal concentration and toxicity. A chromium-reducing bacterial strain, isolated from the vicinity of an electroplate factory, was identified as Ochrobactrum sp. YC211. The efficiency and capacity per time of Ochrobactrum sp. YC211 for hexavalent chromium (Cr(VI)) removal under anaerobic conditions were superior to those under aerobic conditions. An acceptable removal efficiency (96.5 +/- 0.6%) corresponding to 30.2 +/- 0.8 mg-Cr (g-dry cell weight-h)(-1) was achieved by Ochrobactrum sp. YC211 at 300 mg L(-1) Cr(VI). A temperature of 30 degrees C and pH 7 were the optimal parameters for Cr(VI) removal. By examining reactivated cells, permeabilized cells, and cell-free extract, we determined that Cr(VI) removal by Ochrobactrum sp. YC211 under anaerobic conditions mainly occurred in the soluble fraction of the cell and can be regarded as an enzymatic reaction. The results also indicated that an Ochrobactrum sp. YC211 microbial fuel cell (MFC) with an anaerobic anode was considerably superior to that with an aerobic anode in bioelectricity generation and Cr(VI) removal. The maximum power density and Cr(VI) removal efficiency of the MFC were 445 +/- 3.2 mW m(-2) and 97.2 +/- 0.3%, respectively. Additionally, the effects of coexisting ions (Cu(2+), Zn(2+), Ni(2+), SO4(2-), and Cl(-)) in the anolyte on the MFC performance and Cr(VI) removal were nonsignificant (P > 0.05). To our knowledge, this is the first report to compare Cr(VI) removal by different cells and MFC types under aerobic and anaerobic conditions. PMID- 26889694 TI - The role of B. pertussis vaccine antigen gene variants in pertussis resurgence and possible consequences for vaccine development. AB - Whooping cough, or pertussis, caused by Bordetella pertussis is considered resurgent in a number of countries world-wide, despite continued high level vaccine coverage. Among a number of causes for this that have been proposed, is the emergence of B. pertussis strains expressing variants of the antigens contained in acellular pertussis vaccines; i.e. the evolution of B. pertussis toward vaccine escape. This commentary highlights the contradictory nature of evidence for this but also discusses the importance of understanding the role of B. pertussis adaptation to vaccine-mediated immune selection pressures for vaccine-mediated pertussis control strategies. PMID- 26889695 TI - Effects of mechanical stresses on sperm function and fertilization rate in mice. AB - In this study, we investigated whether any of the observed changes in mouse sperm function tests secondary to mechanical stresses (centrifugation and pipetting) correlate with sperm fertilization ability. Chinese Kunming mice were used as sperm and oocyte donors. Sperm samples were allocated evenly into centrifugation, pipette, and control groups. Sperm plasma membrane integrity (PMI), mitochondrial membrane permeability (MMP), baseline and stimulated intracellular ROS, and sperm fertilization ability were measured by hypo-osmotic swelling, flow cytometry, and fertilization tests. Parallel studies were conducted and all tests were repeated six times. Our results showed that after centrifugation, the progressive motility, average path velocity, and overall sperm motility and PMI decreased significantly (p < 0.05). In addition, the MMP level decreased significantly in viable sperm when the centrifugation condition reached 1,400 g * 15 minutes (p < 0.05). When pipetting was performed two or more times, progressive motility, average path velocity, and overall sperm motility decreased significantly (p < 0.05); when it was performed four or more times, sperm membrane integrity and intracellular basal ROS level of viable sperm was also significantly decreased (p < 0.05). In conclusion, various mechanical stresses seem to affect sperm function, however this does not appear to alter fertilization rate. Laboratory handling steps should be minimized to avoid unnecessary mechanical stresses being applied to sperm samples. PMID- 26889696 TI - Function of B-cell lymphoma 6 in trophoblast cells. PMID- 26889702 TI - Intellectual property management in academic drug discovery: what are the challenges? PMID- 26889697 TI - The Swedish joint action method against drink driving-a study of suspected drink drivers' own experiences. AB - OBJECTIVE: In Sweden, a joint action method called SMADIT is in use, where the police quickly offer help from the social services or the dependency care and treatment service to suspected drink drivers. The objective of this article is to analyze the experiences of suspected drink drivers who accepted the offer of help and what it meant for them. The knowledge can be used to improve procedures and consultations. Furthermore, it can allow the basic premises of the method to be examined; for example, the importance of offering help quickly. METHODS: To enable comparisons over time, in-depth interviews were conducted with 12 suspected drink drivers on 2 occasions with 1 year between. RESULTS: To varying degrees the informants knew about their alcohol problems but were unsure whether they would have sought help by themselves. Therefore, the original ideas of the method with an initial contact with the social services or the dependency care and treatment service within 24 h was found to be important. However, the results also showed that some of the informants needed some time before the first meeting because they were in shock from the drink driving incident or in need of sleep. Therefore, the drink driver's situation and individual wishes always have to be considered. The article also shows that an encouraging attitude among the police, the social services, and the dependency care and treatment service is important for the success of the SMADIT method. The informants are satisfied with the method and in retrospect the incident and the SMADIT offer of help are described as a turning point in their lives. One year after being offered help the informants were no longer focused solely on the personal consequences of drink driving, as they were shortly after the incident. Instead, they had gained insights into the harm they could have done to other road users when they drove while drunk. CONCLUSIONS: One conclusion from this article is that SMADIT, as an innovative method that can be deployed more rapidly than other alcohol-impaired driving countermeasures, should be considered as a good complement to conventional methods to deal with drink driving. Based on the results, we recommend a trial of the joint action method against drink driving in other jurisdictions. PMID- 26889698 TI - Increase in Papillary Thyroid Cancer Incidence Is Accompanied by Changes in the Frequency of the BRAF V600E Mutation: A Single-Institution Study. AB - BACKGROUND: Thyroid cancer (TC) has one of the fastest increasing incidences worldwide and primarily involves papillary thyroid cancer (PTC). The BRAF(V600E) mutation is the most common genetic alteration identified in PTC. There are few data concerning an association between the rising incidence of PTC and the increasing prevalence of BRAF-positive cases. Environmental factors such as iodine intake may be responsible for the changing molecular features of PTC. The aim of this study was to evaluate probable variations in the frequency of the BRAF(V600E) mutation in PTC that were diagnosed at a single institution over 14 years in Poland, a country with a demonstrated improvement in iodine supplementation in the early 21st century. METHODS: Time-dependent trends in the prevalence of the BRAF(V600E) mutation during three time periods (2000-2004, 2005 2009, and 2010-2013) were analyzed. The BRAF mutation was genotyped using direct sequencing, allele-specific polymerase chain reaction (PCR), and real-time PCR in 723 unselected cases of PTC that were diagnosed in 2000-2013. Trends in the clinicopathologic characteristics of all PTCs and BRAF(V600E)-positive PTCs were also analyzed. RESULTS: The proportion of PTCs with mutations significantly increased over the study period (54.8% vs. 70.6%; p = 0.001). The median tumor size of all and BRAF-positive tumors decreased (p = 0.008 and p = 0.001, respectively) and correlated with an increase in the proportion of all and mutated microcarcinomas (p = 0.003 and p = 0.003, respectively). A decrease in all and mutated tumors between 2 and 4 cm was also observed (p = 0.002 and p = 0.006, respectively). A significant decrease in tumors >= 4 cm in size was only observed in BRAF-positive cases (p = 0.017). The proportion of classic PTC with BRAF(V600E) mutation was observed to increase (57.6% vs. 74.4%; p = 0.001) and was stable for the follicular variant of PTC (p = 0.336). CONCLUSIONS: The prevalence of the BRAF(V600E)mutation increased significantly in PTCs diagnosed in the authors' institution. Improved detection and several causative factors, most likely environmental and changes in iodine intake, may contribute to the increasing occurrence of TC. PMID- 26889703 TI - Potential pathogenicity of Aeromonas hydrophila complex strains isolated from clinical, food, and environmental sources. AB - Aeromonas are autochthonous inhabitants of aquatic environments, including chlorinated and polluted waters, although they can also be isolated from a wide variety of environmental and clinical sources. They cause infections in vertebrates and invertebrates and are considered to be an emerging pathogen in humans, producing intestinal and extra-intestinal diseases. Most of the clinical isolates correspond to A. hydrophila, A. caviae, and A. veronii bv. Sobria, which are described as the causative agents of wound infections, septicaemia, and meningitis in immunocompromised people, and diarrhoea and dysenteric infections in the elderly and children. The pathogenic factors associated with Aeromonas are multifactorial and involve structural components, siderophores, quorum-sensing mechanisms, secretion systems, extracellular enzymes, and exotoxins. In this study, we analysed a representative number of clinical and environmental strains belonging to the A. hydrophila species complex to evaluate their potential pathogenicity. We thereby detected their enzymatic activities and antibiotic susceptibility pattern and the presence of virulence genes (aer, alt, ast, and ascV). The notably high prevalence of these virulence factors, even in environmental strains, indicated a potential pathogenic capacity. Additionally, we determined the adhesion capacity and cytopathic effects of this group of strains in Caco-2 cells. Most of the strains exhibited adherence and caused complete lysis. PMID- 26889704 TI - Pluripotent Stem Cell-Based Therapies in Combination with Substrate for the Treatment of Age-Related Macular Degeneration. AB - Age-related macular degeneration (AMD) is the leading cause of blindness in the western world, which severely decreases the quality of life in the patients and places an economic burden on their families and society. The disease is caused by the dysfunction of a specialized cell layer in the back of the eye called the retinal pigmented epithelium (RPE). Pluripotent stem cells can provide an unlimited source of RPE, and laboratories around the world are investigating their potential as therapies for AMD. To ensure the precise delivery of functional RPE to the diseased site, some groups are developing a therapy composed of mature RPE monolayers on a supportive scaffold for transplantation as an alternative to injecting a single-cell suspension. This review summarizes methods of generating RPE from pluripotent stem cells, compares biodegradable and biostable materials as scaffolds, and describes the specific combination of human embryonic stem cell-derived RPE on Parylene-C membranes, which is scheduled to begin clinical trials in the United Sates in 2016. Stem cell-derived RPE monolayers on scaffolds hold great promise for the treatment of AMD and other retinal diseases. PMID- 26889706 TI - Temperature-Responsive Switch Constructed from an Anthracene-Functionalized Pillar[5]arene-Based Host-Guest System. AB - A monofunctionalized anthracene pillar[5]arene (MAP5) was designed and synthesized by a click reaction. MAP5 was bound to an ionic liquid through host guest interactions to modify a gold interface. The bonding and release of MAP5 was readily and reversibly controlled by temperature regulation. The developed temperature-responsive switch at an interface can be used in memory storage, drug delivery, and sensing. PMID- 26889705 TI - Priming for tolerance and cohesion at replication forks. AB - Genome duplication is coupled with DNA damage tolerance (DDT) and chromatin structural changes. Recently we reported that mutations in Primase subunits or factors that bridge Polalpha/Primase with the replicative helicase, Ctf4, caused abnormal usage of DDT pathways, negatively influenced sister chromatid cohesion (SCC), and associated with increased fork reversal. (1) We also found that cohesin, which is paradigmatic for SCC, facilitates recombination-mediated DDT. However, only the recombination defects of cohesin, but not of cohesion-defective Polalpha/Primase/Ctf4 mutants, were rescued by artificial tethering of sister chromatids. Genetic tests and electron microscopy analysis of replication intermediates made us propose that management of single-stranded DNA forming proximal to the fork is a critical determinant of chromosome and replication fork structure, and influences DDT pathway choice. Here we discuss the implications of our findings for understanding DDT regulation and cohesion establishment during replication, and outline directions to rationalize the relationship between these chromosome metabolism processes. PMID- 26889707 TI - Excavating the Role of Aloe Vera Wrapped Mesoporous Hydroxyapatite Frame Ornamentation in Newly Architectured Polyurethane Scaffolds for Osteogenesis and Guided Bone Regeneration with Microbial Protection. AB - Guided bone regeneration (GBR) scaffolds are unsuccessful in many clinical applications due to a high incidence of postoperative infection. The objective of this work is to fabricate GBR with an anti-infective electrospun scaffold by ornamenting segmented polyurethane (SPU) with two-dimensional Aloe vera wrapped mesoporous hydroxyapatite (Al-mHA) nanorods. The antimicrobial characteristic of the scaffold has been retrieved from the prepared Al-mHA frame with high aspect ratio (~14.2) via biosynthesis route using Aloe vera (Aloe barbadensis miller) extract. The Al-mHA frame was introduced into an unprecedented SPU matrix (solution polymerized) based on combinatorial soft segments of poly(epsilon caprolactone) (PCL), poly(ethylene carbonate) (PEC), and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, pristine mHA nanorods are also ornamented into it. An enzymatic ring-opening polymerization technique was adapted to synthesize soft segment of (PCL-PEC-b-PDMS). Structure elucidation of the synthesized polymers is established by nuclear magnetic resonance spectroscopy. Sparingly, Al-mHA ornamented scaffolds exhibit tremendous improvement (175%) in the mechanical properties with promising antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast-like MG63 cells (in vitro), the scaffolds were implanted in rabbits as an animal model by subcutaneous and intraosseous (tibial) sites. Improved in vivo biocompatibilities, biodegradation, osteoconductivity, and the ability to provide an adequate biomimetic environment for biomineralization for GBR of the scaffolds (SPU and ornamented SPUs) have been found from the various histological sections. Early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks were found in the defects filled with Al-mHA ornamented scaffold compared to pristine SPU scaffold. Organ toxicity studies further confirm the absence of appreciable tissue architecture abnormalities in the renal hepatic and cardiac tissue sections. The entire results of this study manifest the feasibility of fabricating a mechanically adequate tailored nanofibrous SPU scaffold based on combinatorial soft segments of PCL, PEC, and PDMS by a biomimetic approach and the advantages of an Aloe vera wrapped mHA frame in promoting osteoblast phenotype progression with microbial protection for potential GBR applications. PMID- 26889709 TI - Aquatic Exposure Predictions of Insecticide Field Concentrations Using a Multimedia Mass-Balance Model. AB - Highly complex process-driven mechanistic fate and transport models and multimedia mass balance models can be used for the exposure prediction of pesticides in different environmental compartments. Generally, both types of models differ in spatial and temporal resolution. Process-driven mechanistic fate models are very complex, and calculations are time-intensive. This type of model is currently used within the European regulatory pesticide registration (FOCUS). Multimedia mass-balance models require fewer input parameters to calculate concentration ranges and the partitioning between different environmental media. In this study, we used the fugacity-based small-region model (SRM) to calculate predicted environmental concentrations (PEC) for 466 cases of insecticide field concentrations measured in European surface waters. We were able to show that the PECs of the multimedia model are more protective in comparison to FOCUS. In addition, our results show that the multimedia model results have a higher predictive power to simulate varying field concentrations at a higher level of field relevance. The adaptation of the model scenario to actual field conditions suggests that the performance of the SRM increases when worst-case conditions are replaced by real field data. Therefore, this study shows that a less complex modeling approach than that used in the regulatory risk assessment exhibits a higher level of protectiveness and predictiveness and that there is a need to develop and evaluate new ecologically relevant scenarios in the context of pesticide exposure modeling. PMID- 26889708 TI - The Role of Protein Loops and Linkers in Conformational Dynamics and Allostery. AB - Proteins are dynamic entities that undergo a plethora of conformational changes that may take place on a wide range of time scales. These changes can be as small as the rotation of one or a few side-chain dihedral angles or involve concerted motions in larger portions of the three-dimensional structure; both kinds of motions can be important for biological function and allostery. It is becoming increasingly evident that "connector regions" are important components of the dynamic personality of protein structures. These regions may be either disordered loops, i.e., poorly structured regions connecting secondary structural elements, or linkers that connect entire protein domains. Experimental and computational studies have, however, revealed that these regions are not mere connectors, and their role in allostery and conformational changes has been emerging in the last few decades. Here we provide a detailed overview of the structural properties and classification of loops and linkers, as well as a discussion of the main computational methods employed to investigate their function and dynamical properties. We also describe their importance for protein dynamics and allostery using as examples key proteins in cellular biology and human diseases such as kinases, ubiquitinating enzymes, and transcription factors. PMID- 26889710 TI - Differential Binding Models for Direct and Reverse Isothermal Titration Calorimetry. AB - Isothermal titration calorimetry (ITC) is a technique to measure the stoichiometry and thermodynamics from binding experiments. Identifying an appropriate mathematical model to evaluate titration curves of receptors with multiple sites is challenging, particularly when the stoichiometry or binding mechanism is not available. In a recent theoretical study, we presented a differential binding model (DBM) to study calorimetry titrations independently of the interaction among the binding sites (Herrera, I.; Winnik, M. A. J. Phys. Chem. B 2013, 117, 8659-8672). Here, we build upon our DBM and show its practical application to evaluate calorimetry titrations of receptors with multiple sites independently of the titration direction. Specifically, we present a set of ordinary differential equations (ODEs) with the general form d[S]/dV that can be integrated numerically to calculate the equilibrium concentrations of free and bound species S at every injection step and, subsequently, to evaluate the volume normalized heat signal (deltaQ(V) = deltaq/dV) of direct and reverse calorimetry titrations. Additionally, we identify factors that influence the shape of the titration curve and can be used to optimize the initial concentrations of titrant and analyte. We demonstrate the flexibility of our updated DBM by applying these differentials and a global regression analysis to direct and reverse calorimetric titrations of gadolinium ions with multidentate ligands of increasing denticity, namely, diglycolic acid (DGA), citric acid (CIT), and nitrilotriacetic acid (NTA), and use statistical tests to validate the stoichiometries for the metal ligand pairs studied. PMID- 26889711 TI - Global Introduction of New Multidrug-Resistant Tuberculosis Drugs-Balancing Regulation with Urgent Patient Needs. AB - New treatments for multidrug-resistant tuberculosis (MDR TB) are urgently needed. Two new drugs, bedaquiline and delamanid, have recently been released, and several new drugs and treatment regimens are in the pipeline. Misuse of TB drugs is a principal cause of drug resistance. As new drugs and regimens reach the market, the need to make them available to patients must be balanced with regulation of their use so that resistance to the new drugs can be prevented. To foster the rational use of new drugs, we propose 1) expanding/strengthening the capacity for drug susceptibility testing, beginning with countries with a high TB burden; 2) regulating prescribing practices by banning over-the-counter sale of TB drugs and enacting an accreditation system whereby providers must be certified to prescribe new drugs; and 3) decentralizing MDR TB care in rural communities by employing trained community health workers, using promising mobile technologies, and enlisting the aid of civil society organizations. PMID- 26889712 TI - Tuberculosis Risk among Medical Trainees, Pune, India. AB - During 2012-2013, at a public hospital in Pune, India, 26 (3.9%) cases of tuberculosis were reported among 662 medical trainees, representing an estimated incidence of 3,279 cases/100,000 person-years. Three of these infections were isoniazid-resistant, 1 was multidrug-resistant, and 1 occurred in a trainee who had fulminant hepatitis after starting treatment for TB. PMID- 26889713 TI - Subclinical target organ damage in normotensive and prehypertensive patients. AB - BACKGROUND: Prehypertension is a risk factor for the development of hypertension and other cardiovascular diseases. The objective of this study was to evaluate for the evidence of subclinical target organ damage in two groups of subjects without hypertension. METHODS: This was a prospective cross-sectional study. Subjects seeking care for various clinical conditions in the hospital were invited for the survey. The subjects' were divided in to two groups according to their blood pressure: prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure, 80 to 89 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Urine albumin excretion and other biochemical analyses were performed using standard methods. RESULTS: We recruited a total of 3300 subjects, the prehypertension group included 1100 individuals and the normotension group was composed of 2200 persons. The prevalence of microalbuminuria in subjects in the prehypertension group was 6.8% and in those who are the in the optimal BP group was 3.6% (P<0.001). Subjects in the prehypertension group had a mean B-type natriuretic peptide (BNP) level of 98 (72) pg/mL compared with 43.6 (20) pg/mL found among subjects in the normotension group (<0.001). In the logistic regression model, tobacco smoking aOR 2.7 (95% CI.; 1.7-5.8), higher uric acid level aOR 2.2 (1.7 3.2), microalbuminuria 7.6 (4.9-14.7) and a higher BNP level aOR 2.5 (1.8-7.6) were significantly associated with the occurrence of prehypertension. CONCLUSIONS: Microalbuminuria, BNP level and hyperuricemia were significantly associated with prehypertension. PMID- 26889714 TI - Nepsilon-(carboxymethyl)-lysine, White Matter, and Cognitive Function in Diabetes Patients. AB - OBJECTIVE: To study the relationship of Nepsilon-(carboxymethyl)-lysine level (CML) with microstructure changes of white matter (WM), and cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and to discuss the potential mechanism underlying T2DM-associated cognitive impairment. METHODS: The study was performed in T2DM patients (n=22) with disease course >=5 years and age ranging from 65 to 75 years old. A control group consisted of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML levels were measured by enzyme linked immunosorbent assay, and cognitive function was assessed by Mini-Mental State Examination and Montreal cognitive assessment (MoCA). RESULTS: The total Mini-Mental State Examination score in the patient group (25.72+/-3.13) was significantly lower than the control group (28.16+/-2.45) (p<0.05). In addition, the total MoCA score in the patient group (22.15+/-3.56) was significantly lower than the control group 25.63+/-4.12) (p<0.01). In the patient group, FA values were significantly decreased in the corpus callosum, cingulate fasciculus, inferior fronto-occipital fasciculus, parietal WM, hippocampus, and temporal lobes relative to corresponding regions of healthy controls (p<0.05). Plasma CML level was negatively correlated with average FA values in the global brain (r= 0.58, p<0.01) and MoCA scores (r=-0.47, p<0.05). CONCLUSIONS: In T2DM, WM microstructure changes occur in older patients, and elevations in CML may play a role in the development of cognitive impairment. PMID- 26889717 TI - Sulfuration of the C(sp(2))-H bond of enaminones: a protocol for the synthesis of thioether using elemental sulfur as a sulfurating reagent. AB - Sulfuration reaction of the C(sp(2))-H bond of enaminones with elemental sulfur in the presence of CuBr/K3PO4 was carried out. It provided an efficient method for the synthesis of thioethers in moderate to good yields. The protocol was also applicable to synthesize selenides when selenium powder was used instead of sulfur powder. PMID- 26889716 TI - Quantification of Filamentous Actin (F-actin) Puncta in Rat Cortical Neurons. AB - Filamentous actin protein (F-actin) plays a major role in spinogenesis, synaptic plasticity, and synaptic stability. Changes in dendritic F-actin rich structures suggest alterations in synaptic integrity and connectivity. Here we provide a detailed protocol for culturing primary rat cortical neurons, Phalloidin staining for F-actin puncta, and subsequent quantification techniques. First, the frontal cortex of E18 rat embryos are dissociated into low-density cell culture, then the neurons grown in vitro for at least 12-14 days. Following experimental treatment, the cortical neurons are stained with AlexaFluor 488 Phalloidin (to label the dendritic F-actin puncta) and microtubule-associated protein 2 (MAP2; to validate the neuronal cells and dendritic integrity). Finally, specialized software is used to analyze and quantify randomly selected neuronal dendrites. F-actin rich structures are identified on second order dendritic branches (length range 25-75 um) with continuous MAP2 immunofluorescence. The protocol presented here will be a useful method for investigating changes in dendritic synapse structures subsequent to experimental treatments. PMID- 26889718 TI - Application of Biologically Based Lumping To Investigate the Toxicokinetic Interactions of a Complex Gasoline Mixture. AB - People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. We developed an approach that applies chemical lumping methods to complex mixtures, in this case gasoline, based on biologically relevant parameters used in physiologically based pharmacokinetic (PBPK) modeling. Inhalation exposures were performed with rats to evaluate the performance of our PBPK model and chemical lumping method. There were 109 chemicals identified and quantified in the vapor in the chamber. The time-course toxicokinetic profiles of 10 target chemicals were also determined from blood samples collected during and following the in vivo experiments. A general PBPK model was used to compare the experimental data to the simulated values of blood concentration for 10 target chemicals with various numbers of lumps, iteratively increasing from 0 to 99. Large reductions in simulation error were gained by incorporating enzymatic chemical interactions, in comparison to simulating the individual chemicals separately. The error was further reduced by lumping the 99 nontarget chemicals. The same biologically based lumping approach can be used to simplify any complex mixture with tens, hundreds, or thousands of constituents. PMID- 26889719 TI - Computational Revisit to the beta-Carbon Elimination Step in Rh(III)-Catalyzed C H Activation/Cycloaddition Reactions of N-Phenoxyacetamide and Cyclopropenes. AB - This computational study uncovered the origin of the contradicting results in two recent DFT studies of the Rh(III)-catalyzed C-H activation/cycloaddition reactions between N-phenoxyacetamide and cyclopropenes. It was found that the beta-carbon elimination of the tricyclic intermediate occurs very faciely via a conformer in which the opening of the three-membered ring is trans to the Cp* ligand so that the steric repulsion between the two moieties is avoided. Thus, the conclusions of our previous study were reconfirmed. PMID- 26889720 TI - Metabolomics Study of Roux-en-Y Gastric Bypass Surgery (RYGB) to Treat Type 2 Diabetes Patients Based on Ultraperformance Liquid Chromatography-Mass Spectrometry. AB - Roux-en-Y gastric bypass (RYGB) is one of the most effective treatments for long term weight loss and diabetes remission; however, the mechanisms underlying these changes are not clearly understood. In this study, the serum metabolic profiles of 23 remission and 12 nonremission patients with type 2 diabetes mellitus (T2DM) were measured at baseline, 6- and 12-months after RYGB. A metabolomics analysis was performed based on ultra-performance liquid chromatography-mass spectrometry. Clinical improvements in insulin sensitivity, energy metabolism, and inflammation were related to metabolic alterations of free fatty acids (FFAs), acylcarnitines, amino acids, bile acids, and lipids species. Differential metabolic profiles were observed between the two T2DM subgroups, and patients with severity fat accumulation and oxidation stress may be more suitable for RYGB. Baseline levels of tryptophan, bilirubin, and indoxyl sulfate measured prior to surgery as well as levels of FFA 16:0, FFA 18:3, FFA 17:2, and hippuric acid measured at 6 months after surgery best predicted the suitability and efficacy of RYGB for patients with T2DM. These metabolites represent potential biomarkers that may be clinically helpful in individualized treatment for T2DM patients by RYGB. PMID- 26889721 TI - Lyme Disease in Hispanics, United States, 2000-2013. AB - Hispanics comprise a growing portion of the US population and might have distinct risk factors for tickborne diseases. During 2000-2013, a total of 5,473 Lyme disease cases were reported among Hispanics through national surveillance. Hispanics were more likely than non-Hispanics to have signs of disseminated infection and onset during fall months. PMID- 26889722 TI - Wohlfahrtiimonas chitiniclastica Infections in 2 Elderly Patients, Hawaii. PMID- 26889723 TI - Cancer surveillance series: role of demographic aspects, altitude and latitude in the extracutaneous malignant melanoma in a residential study. AB - BACKGROUND: Extracutaneous melanoma (ECM) is a very rare malignancy and its biology differs from that of cutaneous melanoma. Residential studies can offer an important contribution to the study of this disease. METHODS: We characterized the distribution of ECM according to residential and demographic baseline characteristics. We computer-searched patients that removed an ECM, and we analyzed all demographic and residential parameters. Disease free survival (DFS), date of death or last follow-ups were evaluated. The same parameters were analyzed using hazards-regression. Finally, we used the multiple regressions between DFS and the predictors. RESULTS: A total of 44 ECM patients were included in our analysis. Median DFS was of 10 months; at Log-Rank Test and Cox-hazard regression, the variable age (P<0.01; P<0.004) and latitude (P<0.02; P<0.006) reached a statistical significance; at multiple logistic regression, the significance was instead maintained only for the variable age. General OS was of 42 months at Log-Rank Test age (P<0.001), as well as latitude (P<0.006) maintained its significance at hazard-regression. CONCLUSIONS: Demographic and residential aspects can play an important role in the study of this rare disease, supporting the assumption that ECM are generated by processes actually unknown, as demonstrated in our results compared with those of the literature. PMID- 26889724 TI - Efficacy and safety of a 12-month treatment with a combination of hydroxypinacolone retinoate and retinol glycospheres as maintenance therapy in acne patients after oral isotretinoin. AB - BACKGROUND: A correct therapeutic management of acne should include a maintenance therapy to prevent recurrences after discontinuing a successful treatment. The aim of this study is to investigate efficacy and safety of a 12-month maintenance treatment with a product, based on Retinsphere technology that combines retinol encapsulated in glycospheres and hydroxypinacolone retinoate (Biretix gel(r)), to control acne relapse after a treatment with oral isotretinoin (O.I.). METHODS: The study consisted of 2 phases: active treatment phase (AP) and maintenance phase (MP). In the AP, 40 consecutive patients with moderate facial acne were treated with O.I. until acne remission. Then, the patients entered in the MP and were treated with Biretix gel(r) once-daily for 12 months. The efficacy parameter was the relapse rate during MP. RESULTS: Thirty-nine patients completed the study. Relapse appeared in 6 patients (15.38%). The new product with Retinsphere technology was well tolerated and none of the subjects complained of adverse events. CONCLUSIONS: Our findings seems to provide favorable evidence of the efficacy and the safety of this new product in the maintenance treatment after O.I. in patient with moderate acne. The efficacy is maintain for a period as long as a year after O.I. suspension. PMID- 26889725 TI - Etiopathogenesis of rosacea: a prospective study with a three-year follow-up. AB - BACKGROUND: The aim of this study was to investigate the role of Demodex folliculorum (DF), Helicobacter pylori (HP), and small intestine bacterial overgrowth (SIBO) in the development of rosacea. METHODS: A case-control study including 60 patients with rosacea and 40 healthy controls was performed. All the patients underwent standardized skin surface biopsy to investigate DF, urea breath test for HP and lactulose breath test and glucose breath test for SIBO. Etiological therapy was started in the following order: acaricidal treatment, antibiotics for SIBO and HP. These exams were repeated after 3 years. Statistical analysis was performed. RESULTS: As regards the 88 patients who completed the entire follow-up, DF positivity was found in 47.7% of the patients, SIBO in 25.0%, and HP in 21.6%. SIBO significantly prevailed in papulopustular rosacea, while HP in erythrosis. At the 6-month follow up, the 61% of patients were in remission. After 3 years, 18% of patients dropped out, while the remaining patients repeated all the investigations. The majority of patients were still in remission and negative for HP while only 5 were positive for DF and 4 for SIBO. CONCLUSIONS: SIBO was the most relevant factor in papulopustular rosacea. Its treatment was crucial in improvement and in maintaining the clinical remission. PMID- 26889726 TI - Non-melanoma skin cancer of the head and neck: the aid of reflectance confocal microscopy for the accurate diagnosis and management. AB - BACKGROUND: Non-melanoma skin cancer (NMSC) represents the most common cutaneous neoplasms of the head and neck. In recent years, novel non-invasive diagnostic tool have been developed, and among these we have the reflectance confocal microscopy (RCM), that offers the evaluation of the skin at real time with cellular resolution. Numerous studies have identified the main confocal features of skin tumours, demonstrating the good correlation of these features with certain dermatoscopic patterns and histologic findings. EVIDENCE ACQUISITION: The aim of this analysis was to provide new insight into the role of RCM in the diagnosis and management of NMSC of the head and neck. Data comes from the most recent literature, taking into account previous essential reported information in this field. The study eligibility criteria were: studies providing update information, focusing on RCM findings in NMSC, without restrictions for age, sex, ethnicity. A search concerning the role of dermoscopy and RCM in the diagnosis of NMSC was performed on Medline. Duplicated studies, single case report and papers with language other than English were excluded from this study. EVIDENCE SYNTHESIS: RCM clues were analysed for NMSC in association with clinical, dermoscopic and histopathologic findings. Moreover, some new findings have been described and possible applications for NMSC of the head and neck have been discussed. CONCLUSIONS: RCM allows tissue imaging in vivo contributing to a more accurate diagnosis of NMSC of the head and neck, sparing time for the patient and costs for the public health system. RCM can also be used for selection of the biopsy site and it is helpful in defining the surgical safety margins to keep during the excision of skin cancers. PMID- 26889727 TI - A review of clinical trials of biologic agents and small molecules for psoriasis in Asian subjects. AB - INTRODUCTION: Biologics are increasingly used in the treatment of moderate to severe psoriasis. However, most of the pivotal studies were performed mainly in western countries. The purpose of this review article was to compare the differences of clinical trial results between Asian and Western subjects of psoriasis regarding baseline demographics, efficacy, dermatology life quality index, safety and antidrug antibodies. EVIDENCE ACQUISITION: In this review article, we searched the PubMed/Medline, ClinicalTrials.gov, and posters from main dermatologic meetings. EVIDENCE SYNTHESIS: Only randomized controlled trial results or trial results for registration purposes of etanercept, adalimumab, infliximab, ustekinumab, secukinumab, brodalumab, ixekizumab, guselkumab, tofacitinib, and apremilast are included. CONCLUSIONS: Asian subjects were generally 15-20 Kgs lighter, with fewer psoriatic arthritis, shorter disease duration since diagnosis, and higher baseline severity compared to western subjects. Better efficacy had been found in some studies such as secukinumab, brodalumab, ixekizumab, and tofacitinib in Japanese groups. The safety in Asian trials was generally compatible with the pivotal studies, except for the occurrence of active tuberculosis in the infliximab trial in China. Additional indications of pustular and erythrodermic psoriasis are approved in Japan for some of the agents based on phase II/III studies. PMID- 26889728 TI - Improved Detection of Tuberculosis and Multidrug-Resistant Tuberculosis among Tibetan Refugees, India. AB - The incidence of tuberculosis (TB) among Tibetan refugees in India is 431 cases/100,000 persons, compared with 181 cases/100,000 persons overall in India in 2010. More than half of TB cases in these refugees occur among students, monks, and nuns in congregate settings. We sought to increase TB case detection rates for this population through active case finding and rapid molecular diagnostics. We screened 27,714 persons for symptoms of TB and tested 3,830 symptomatic persons by using an algorithm incorporating chest radiography, sputum smear microscopy, culture, and a rapid diagnostic test; 96 (2.5%) cases of TB were detected (prevalence 346 cases/100,000 persons). Of these cases, 5% were multidrug-resistant TB. Use of the rapid diagnostic test and active case finding enabled rapid detection of undiagnosed TB cases in congregate living settings, which would not have otherwise been identified. The burden of TB in the Tibetan exile population in India is extremely high and requires urgent attention. PMID- 26889729 TI - Environmental analysis of the life cycle emissions of 2-methyl tetrahydrofuran solvent manufactured from renewable resources. AB - An environmental analysis has been conducted to determine the cradle to gate life cycle emissions to manufacture the green solvent, 2-methyl tetrahydrofuran. The solvent is considered a greener chemical since it can be manufactured from renewable resources with a lower life cycle footprint. Analyses have been performed using different methods to show greenness in both its production and industrial use. This solvent can potentially be substituted for other ether and chlorinated solvents commonly used in organometallic and biphasic reactions steps in pharmaceutical and fine chemical syntheses. The 2-methyl tetrahydrofuran made from renewable agricultural by-products is marketed by Penn A Kem under the name ecoMeTHFTM. The starting material, 2-furfuraldehyde (furfural), is produced from corn cob waste by converting the available pentosans by acid hydrolysis. An evaluation of each step in the process was necessary to determine the overall life cycle and specific CO2 emissions for each raw material/intermediate produced. Allocation of credits for CO2 from the incineration of solvents made from renewable feedstocks significantly reduced the overall carbon footprint. Using this approach, the overall life cycle emissions for production of 1 kg of ecoMeTHFTM were determined to be 0.191 kg, including 0.150 kg of CO2. Life cycle emissions generated from raw material manufacture represents the majority of the overall environmental impact. Our evaluation shows that using 2-methyl tetrahydrofuran in an industrial scenario results in a 97% reduction in emissions, when compared to typically used solvents such as tetrahydrofuran, made through a conventional chemical route. PMID- 26889730 TI - Bio-psycho-social effects of a coordinated neurorehabilitation programme: A naturalistic mixed methods study. AB - PURPOSE: Best practice guidelines for neurorehabilitation recommend coordinated rehabilitation programmes to ensure seamless service transitions and comprehensive rehabilitation practices. However, this recommendation for practice and the evidence informing its advancement is based on unexamined assumptions. Therefore, this study investigates bio-psycho-social outcomes and perceptions of a coordinated rehabilitation programme. METHOD: In a prospective, naturalistic mixed methods study, rehabilitation outcomes for 82 adults (18-66 years) with moderate to severe acquired brain injury were investigated. Clients who received the coordinated rehabilitation programme KORE (n = 27) were compared to clients from the same area who received standard rehabilitation prior to the implementation of the KORE programme (n = 37) and clients who received other coordinated efforts elsewhere (n = 18). The study employed quantitative data from standardized tests (Functional Independence Measure, Major Depression Inventory, Quality of life, and Impact on Participation and Autonomy Questionnaire, as well as information on return to work and qualitative interviews with clients (n = 82) and their relatives (n = 40). RESULTS: Outcomes did not improve from hospital discharge to two years later. Notably, physiological recovery had probably been achieved to the extent possible, but depression and reduced psychological well being remained prevalent across groups. Qualitative interviews suggested several barriers to improvement, such as identity dilemmas and unmet needs for psychological support, while rehabilitation services focused on physical and practical training. CONCLUSION: Coordinated interventions do not guarantee comprehensive rehabilitation and better outcomes for clients with acquired brain injury. Psychological support seems to be important and largely unaddressed. PMID- 26889731 TI - Functional cerebral space theory: Towards an integration of theory and mechanisms of left hemineglect, anosognosia, and anosodiaphoria. AB - BACKGROUND: The current case study presents a 43 year old African American woman admitted to a Tertiary Care Rehabilitation unit at a major medical center for concerns over left-sided anesthesia and weakness. Head scans indicate a right middle cerebral arterial distribution infarct altering blood flow in temporal, parietal, and occipital regions in the right cerebral hemisphere. OBJECTIVE: Physician and therapist reports (i.e., speech and occupational therapists) referred the patient for a neuropsychological evaluation for concerns over the patient's capacity to recognize the severity of her deficits and self-care, with potential rule-outs indicated by the extant literature on right CVA for anosognosia, anosodiaphoria, and left hemibody/hemispace neglect. METHODS: The current case integrates interdisciplinary physician notation, magnetic resonance imaging and magnetic resonance angiogram, observations and reports from speech and occupational therapy, and neuropsychological assessment via standardized tests and neurobehavioral syndrome analysis. RESULTS: Evidence was found for co occurring syndromes of moderate anosognosia, anosodiaphoria, and left hemibody/hemispatial neglect derived from shared functional cerebral space with overlapping temporal, parietal, and occipital damage. CONCLUSIONS: Clinical implications are discussed, including recommendations for therapy approaches based on functional cerebral space theory that may indicate the use of known techniques (e.g., for left hemibody neglect) that may also have therapeutic implications for treating other, more mercurial co-occurring syndromes of anosognosia and anosodiaphoria. PMID- 26889732 TI - Effect of normal-walking-pattern-based functional electrical stimulation on gait of the lower extremity in subjects with ischemic stroke: A self controlled study. AB - BACKGROUND: Functional electrical stimulation is a widely used technique for rehabilitation. OBJECTIVE: To assess the efficacy of walking-pattern-based four channel functional electric stimulation and its influence on the gait features of stroke patients with hemiplegia. METHODS: A total of 21 stroke patients with hemiplegia were enrolled into the study. The walking gaits of patients were investigated before, during and after walking-pattern-based FES treatment using the gait analysis system. The changes of gait indexes were comparatively analyzed. RESULTS: After walking-pattern-based FES therapy, the pace, stride rate, gait cycle, and step length of stroke patients with hemiplegia were 50.19 +/- 14.45 cm/s, 36.85 +/- 5.85 time/min, 1.6643 +/- 0.2626 sec, 80.3333 +/- 15.1438 cm, respectively. The motion range of hip and knee joint were 47.5238 +/- 10.7453, 56.7619 +/- 14.5255, respectively. We found these indexes were significantly improved compared with those before FES treatment (P < 0.05). The single swing rate (injured extremity/uninjured extremity) after FES treatment was 1.5589 +/- 0.4550. The statistical results showed that the gait cycle, pace, stride rat, and single swing rate (injured extremity/uninjured extremity) were significantly improved after FES treatment (P < 0.05). CONCLUSIONS: Our results demonstrate that walking-paradigm based FES we developed is effective for treating stroke patients during rehabilitation. PMID- 26889734 TI - Cross-validation of oxygen uptake prediction during walking in ambulatory persons with multiple sclerosis. AB - BACKGROUND: An equation for predicting the gross oxygen uptake (gross-VO2) during walking for persons with multiple sclerosis (MS) has been developed. Predictors included walking speed and total score from the 12-Item Multiple Sclerosis Walking Scale (MSWS-12). OBJECTIVE: This study examined the validity of this prediction equation in another sample of persons with MS. METHODS: Participants were 18 persons with MS with limited mobility problems (42 +/- 13 years; 14 women). Participants completed the MSWS-12. Gross-VO2 was measured with open circuit spirometry during treadmill walking at 2.0, 3.0, and 4.0 mph (0.89, 1.34, and 1.79 m.s(-1)). REULTS: Absolute percent error was small: 8.3 +/- 6.1% , 8.0 +/- 5.6% , and 12.2 +/- 9.0% at 2.0, 3.0, and 4.0 mph, respectively. Actual gross VO2 did not differ significantly from predicted gross-VO2 at 2.0 and 3.0 mph, but was significantly higher than predicted gross-VO2 at 4.0 mph (p < 0.001). Bland Altman plots indicated nearly zero mean difference between actual and predicted gross-VO2 with modest 95% confidence intervals at 2.0 and 3.0 mph, but there was some underestimation at 4.0 mph. CONCLUSIONS: Speed and MSWS-12 score provide valid prediction of gross-VO2 during treadmill walking at slow and moderate speeds in ambulatory persons with MS. However, there is a possibility of small underestimation for walking at 4.0 mph. PMID- 26889733 TI - A durable gain in motor and non-motor symptoms of Parkinson's Disease following repeated caloric vestibular stimulation: A single-case study. AB - OBJECTIVE: To gain 'first-in-man' evidence that repeated caloric vestibular stimulation (CVS), a non-invasive form of neuro-modulation, can induce a lasting and clinically-relevant reduction in Parkinson's Disease (PD) symptoms. METHODS: A 70 yr old male, diagnosed with PD 7 years prior to study enrolment, self administered CVS at home 2*20 minutes per day for three months using a solid state portable device. Standardised neuropsychological assessments of motor, cognitive, affective and independent function were carried out prior to stimulation, at the start and end of the sham (month 1) and active (months 2-3) phases, and 5 months post-stimulation. RESULTS: Relative to the pre-stimulation baseline, behavioural improvements that exceeded the minimal detectable change were observed on the EQ5D, Unified Parkinson's Disease Rating Scale, Schwab and England scale, 2 minute walk, Timed up and go, Non-motor symptom assessment scale for PD, Montreal cognitive assessment, Hospital depression scale and Epworth sleepiness scale. The level of change exceeded the threshold for a minimal clinically important difference on all scales for which a threshold has been published. By contrast, little improvement was seen during the sham (i.e., placebo) phase. CONCLUSION: Caloric vestibular stimulation may offer a novel, home-based method of relieving everyday symptoms of PD, and merits further evaluative study. PMID- 26889736 TI - Testing Tactile Masking between the Forearms. AB - Masking, in which one stimulus affects the detection of another, is a classic technique that has been used in visual, auditory, and tactile research, usually using stimuli that are close together to reveal local interactions. Masking effects have also been demonstrated in which a tactile stimulus alters the perception of a touch at a distant location. Such effects can provide insight into how components of the body's representations in the brain may be linked. Occasional reports have indicated that touches on one hand or forearm can affect tactile sensitivity at corresponding contralateral locations. To explore the matching of corresponding points across the body, we can measure the spatial tuning and effect of posture on contralateral masking. Careful controls are required to rule out direct effects of the remote stimulus, for example by mechanical transmission, and also attention effects in which thresholds may be altered by the participant's attention being drawn away from the stimulus of interest. The use of this technique is beneficial as a behavioural measure for exploring which parts of the body are functionally connected and whether the two sides of the body interact in a somatotopic representation. This manuscript describes a behavioural protocol that can be used for studying contralateral tactile masking. PMID- 26889738 TI - Phage-displayed macrocyclic glycopeptide libraries. AB - In this report, we describe an efficient way to generate libraries of macrocyclic glycopeptides in one step by reacting phage-displayed libraries of peptides with dichloro-oxime derivatives. We showed that the reactions do not interfere with the ability of phage to replicate in bacteria. The reactions are site-selective for phage-displayed peptides and they do not modify any other proteins of phage. The technology described in this report will be instrumental for genetic selection of macrocyclic glycopeptides for diverse glycan-binding proteins. PMID- 26889735 TI - BDNF rs6265 methylation and genotype interact on risk for schizophrenia. AB - Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation. We found that methylation at the BDNF rs6265 Val allele in peripheral blood of healthy subjects is associated with hypoxia-related early life events (hOCs) and intermediate phenotypes for schizophrenia in a distinctive manner, depending on rs6265 genotype: in ValVal individuals increased methylation is associated with exposure to hOCs and impaired working memory (WM) accuracy, while the opposite is true for ValMet subjects. Also, rs6265 methylation and hOCs interact in modulating WM-related prefrontal activity, another intermediate phenotype for schizophrenia, with an analogous opposite direction in the 2 genotypes. Consistently, rs6265 methylation has a different association with schizophrenia risk in ValVals and ValMets. The relationships of methylation with BDNF levels and of genotype with BHLHB2 binding likely contribute to these opposite effects of methylation. We conclude that BDNF rs6265 methylation interacts with genotype to bridge early environmental exposures to adult phenotypes, relevant for schizophrenia. The study of epigenetic changes in regions containing genetic variation relevant for human diseases may have beneficial implications for the understanding of how genes are actually translated into phenotypes. PMID- 26889737 TI - Low antibody titers 5 years after vaccination with the CYD-TDV dengue vaccine in both pre-immune and naive vaccinees. AB - Globally, dengue virus (DENV) is one of the most widespread vector-borne viruses. Dengue disease affects populations in endemic areas and, increasingly, tourists who travel to these countries, but there is currently no approved vaccine for dengue. A phase 3 efficacy trial with Sanofi-Pasteur's recombinant, live attenuated, tetravalent dengue vaccine (CYD-TDV) conducted in South East Asia showed an overall efficacy of 56% against virologically confirmed dengue infections of any severity and any of the 4 serotypes, but the long-term protection of the vaccine has yet to be demonstrated. To address longevity of antibody titers and B cell memory, we recalled study participants from an earlier CYD immunogenicity study (Phase 2) conducted in Singapore that enrolled healthy volunteers in the year 2009. Depending on the age group, 57-84% of the participants initially generated a neutralizing antibody titer >= 10 to all 4 DENV serotypes 28 d after the third and final dose. We observed very low antibody titers in blood samples collected from 23 vaccinees 5 y after the first dose, particularly titers of antibodies binding to virus particles compared with those binding to recombinant E protein. The in vivo efficacy of plasma antibodies against DENV-2 challenge was also tested in a mouse model, which found that only 2 out of 23 samples were able to reduce viremia. Although the sample size is too small for general conclusions, dengue immune memory after vaccination with CYD TDV appears relatively low. PMID- 26889739 TI - Small cell carcinoma of the urinary bladder: changing trends in the current literature. AB - Background Extrapulmonary small cell carcinoma (SmCC), also known as oat cell carcinoma or small cell neuroendocrine carcinoma, is characterized by an aggressive clinical course with early metastasis pattern and a short life expectancy. So far, there is no prospective, data-based case-control study due to its low incidence. The purpose of this paper is to discuss the epidemiology, morphopathology, clinical characteristics, differential diagnosis and treatment of bladder SmCC in the light of the literature. Scope PubMed and American Society of Clinical Oncology Meeting abstracts were searched according to the following keywords: 'extrapulmonary SmCC', 'bladder cancer', and 'therapeutic approach'. The last search was performed on 1 October 2015. Some additional papers were determined by reviewing references of the appropriate articles. Most of the data regarding small cell carcinoma of the urinary bladder (SmCCB) were found to be based on the retrospective trials. Findings Bladder SmCC is more frequent in men and usually appears in the seventh to eighth decades. Macroscopic hematuria is the most common clinical symptom. The diagnosis of SmCCB is performed based on the same criteria determined by the WHO classification for the diagnosis of small cell lung carcinoma (SCLC). Prognosis is closely correlated with the stage at presentation. Although the prognosis of the disease is poor, a long survival can be achieved particularly by radical surgery following neoadjuvant chemotherapy in patients with early stage tumors. Cystectomy is still the current standard local treatment. However, cystectomy alone is not sufficient. Chemotherapy and definitive radiotherapy should be preferred for limited disease in patients who are not candidate for surgery. Conclusion Considering the poor prognosis of the disease, further studies are needed to determine the optimal treatment options and new molecular markers in the way of early diagnosis and favorable outcomes. Prospective, multicenter, randomized studies are required to evaluate the role of neoadjuvant chemotherapy followed either by surgery or radiotherapy. PMID- 26889740 TI - Oral aspirin for treating venous leg ulcers. AB - BACKGROUND: Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwide; prevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. OBJECTIVES: To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. SEARCH METHODS: In May 2015 we searched: The Cochrane Wounds Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for published or ongoing trials. There were no language or publication date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared oral aspirin with placebo or no drug intervention (in the presence or absence of compression therapy) for treating people with venous leg ulcers. Our main outcomes were time to complete ulcer healing, rate of change in the area of the ulcer, proportion of ulcers healed in the trial period, major bleeding, pain, mortality, adverse events and ulcer recurrence (time for recurrence and proportion of recurrence). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial and assessed overall quality of evidence for the main outcomes in the 'Summary of findings' table. MAIN RESULTS: The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group . Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated.In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in addition to compression bandages with compression alone over a five month period. There was little difference in complete healing rates between groups (21/28 aspirin and 17/23 compression bandages alone) but the average time to healing was shorter (12 weeks in the treated group vs 22 weeks in the compression only group) and the average time for recurrence was longer in the aspirin group (39 days: [SD 6.0] compared with 16.3 days [SD 7.5] in the compression only group). Although this trial provides some limited data about the potential use of aspirin therapy, the sample size (only 20 patients) was too small for us to draw meaningful conclusions. In addition, patients were only followed up for 4 months and no information on placebo was reported. AUTHORS' CONCLUSIONS: Low quality evidence from two trials indicate that there is currently insufficient evidence for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. We downgraded the evidence to low quality due to potential selection bias and imprecision due to the small sample size. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, we are unable to draw conclusions about the benefits and harms of oral daily aspirin as an adjunct to compression in VLU healing or recurrence. Further high quality studies are needed in this area. PMID- 26889741 TI - Clinical outcomes of frozen-thawed single blastocyst transfer in patients requiring whole embryo freezing. AB - We compared clinical outcomes amongst frozen-thawed cleavage-stage embryo, double and single blastocyst transfers in patients requiring whole embryo freezing. Data of infertile patients undergoing in-vitro fertilization and embryo transfer (IVF ET) in our Reproductive Medicine Center from January 2010 to December 2012 were retrospectively analyzed. According to patients' wishes, patients were divided into cleavage-stage embryo transfer groups (group A, n = 456), double blastocyst transfer group (group B, n = 106), and single blastocyst transfer group (group C, n = 402). We found that the number of frozen embryos was significantly less in groups B and C than in group A (all p < 0.05), but the implantation rate was significantly higher in groups B and C as compared to group A (all p < 0.05). The clinical pregnancy rate and pregnancy rate per included cycle were significantly higher in group B than in groups A and C (all p < 0.05). The multiple pregnancy rate was significantly lower in group C than in groups A and B (all p < 0.05). The rate of early abortion was significantly lower in group C as compared to group A (p < 0.05). The data support the view that it may be the best clinical strategy for patients who require whole embryo freezing and have four or more Day 3 embryos available, to incubate Day 3 embryos into blastocysts, which are then vitrified for elective single blastocyst transfer. PMID- 26889743 TI - Treatment of ichthyosis and hypernatremia in a patient with Netherton syndrome with a SPINK5 c.153delT mutation using kallikrein inhibiting ointment. PMID- 26889744 TI - Early and Late Outcomes of Aortic Valve Replacement Using Bioprosthetic Versus Mechanical Valve in Elderly Patients: A Propensity Analysis. AB - BACKGROUND AND AIM OF THE STUDY: There is still controversy on the use of mechanical valves to treat elderly patients with a small aortic annulus who require aortic valve replacement (AVR). We compared our results in elderly patients who underwent AVR with a bioprosthetic or mechanical valve. Propensity matching adjusted for baseline differences in this study. METHODS: Between January 2001 and July 2014, 277 patients aged >=75 years old who underwent AVR were enrolled. Of 277 patients, 104 patients were selected using propensity score matching analysis. Out of this cohort, 52 patients underwent AVR with a bioprosthetic valve (B group) and the remainder AVR with a mechanical valve (M group). RESULTS: There were no significant differences between the B and M groups in 30 days mortality (1.9% vs. 5.8%, p = 0.618). The incidence of patient prosthesis mismatch (PPM) after AVR tended to be lower in the M group than in the B group. The overall survival rates in the B and M groups at eight years were 72.8% and 73.3%, respectively (p = 0.473). No significant differences between the two groups were observed in freedom from valve-related death, cardiac events, bleeding events, or stroke events. CONCLUSIONS: AVR in elderly patients achieved relatively good short-term and long-term outcomes, and the incidence rates of valve-related complications after using a mechanical valve were low. In a selected population of elderly patients, a mechanical valve may be acceptable. doi: 10.1111/jocs.12719 (J Card Surg 2016;31:195-202). PMID- 26889745 TI - Correlation between transvaginal ultrasound measured endometrial thickness and histopathological findings in Turkish women with abnormal uterine bleeding. AB - AIM: The present study aims to determine how transvaginal ultrasonography and histopathological examination findings are correlated in a cohort of premenopausal and postmenopausal Turkish women with abnormal uterine bleeding. METHODS: This is a retrospective review of 350 Turkish women who underwent transvaginal ultrasonography and suction curettage as a result of abnormal uterine bleeding. RESULTS: Sonographic appearance of the endometrium was normal in 244 patients (69.7%), while homogeneous thickening was detected in 47 patients (13.4%) and cystic thickening in 21 patients (6.0%). A sonographic diagnosis of endometrial polyp was made in 38 patients (10.9%). Histopathological analysis of endometrial samplings revealed proliferative endometrium (36%), secretory endometrium (24.6%), decidualization (10.9%), endometrial polyp (8.3%), endometritis (6.8%), endometrial hyperplasia (4.6%), irregular shedding (3.7%), atrophic endometrium (3.1%), endometrial cancer (1.1%) and placental retention (0.9%). The sonographic and histopathological findings correlated significantly (chi(2) = 122 768, P = 0.001; r = 0.215, P = 0.001). Approximately 51% of the women with homogeneous endometrial thickening had proliferative endometrium. Only 44.7% of the women with ultrasonographically visualized endometrial polyps had histopathologically diagnosed endometrial polyps. Nearly 57% of the women with cystic endometrial thickening had proliferative endometrium. CONCLUSION: If there is no facility for hysteroscopy or hysteroscopy-guided endometrial biopsy for women with abnormal uterine bleeding, transvaginal ultrasonography findings can be efficiently used to make a preliminary diagnosis and, thus, notify the pathologists. PMID- 26889742 TI - 'She believed in me'. What patients with depression value in their relationship with practitioners. A secondary analysis of multiple qualitative data sets. AB - BACKGROUND: Clinical guidance promotes the practitioner-patient relationship as integral to good quality person-centred care for patients with depression. However, patients can struggle to engage with practitioners and practitioners have indicated that they want more guidance on how to establish effective relationships with their patients. OBJECTIVE: To identify what practitioner attributes patients with depression particularly value or find problematic. METHOD: A secondary analysis of data collected during four qualitative studies, all of which entailed interviewing patients diagnosed with depression about their treatment experiences. Patients in the four studies had received different treatments. These included antidepressants, cognitive behaviour therapy, facilitated physical activity and listening visits. We thematically analysed 32 patient accounts. RESULTS: We identified two complimentary sets of important practitioner attributes: the first based on the practitioner's bearing; the second based on the practitioner's enabling role. We found that patients value practitioners who consider their individual manner, share relevant personal information, show interest and acceptance, communicate clearly and listen carefully, collaborate on manageable goals and sanction greater patient self-care and self-compassion. It was also evident that patients receiving different treatments value the same practitioner attributes and that when these key practitioner qualities were not evident, patients were liable not to re-attend or comply with treatment. CONCLUSION: The practitioner attributes that patients with depression most value have a positive impact on their engagement with treatment. Patients emphasise the importance of a practitioner's demeanour and encouragement, rather than the amount of time or specific treatment a practitioner is able to provide. PMID- 26889746 TI - Z-Shaped Pyrrolo[3,2-b]pyrroles and Their Transformation into pi-Expanded Indolo[3,2-b]indoles. AB - Sterically hindered 1,4-dihydropyrrolo[3,2-b]pyrroles possessing ortho (arylethynyl)phenyl substituents at positions-2 and -5 were efficiently synthesized through a sila-Sonogashira reaction. These unique Z-shaped dyes showed relatively strong fluorescence in solution. Detailed optimization revealed that, in the presence of InCl3, these alkynes readily undergo an intramolecular double cyclization to give hexacyclic products bearing an indolo[3,2-b]indole skeleton in remarkable yields. Steady-state UV-visible spectroscopy revealed that upon photoexcitation, the prepared Z-shaped alkynes undergo mostly radiative relaxation leading to high fluorescence quantum yields. In the case of 7,14 dihydrobenzo[g]benzo[6,7]indolo[3,2-b]indoles, we believe that the substantial planarization of geometry in the excited state, is the underlying reason for the observed large Stokes shifts. The presence of additional electron-withdrawing groups makes it possible to further alter the photophysical properties. The two photon absorption cross-section values of both families of dyes were found to be modest and the nature of the excited state responsible for two-photon absorption appeared to be strongly affected by the presence of peripheral groups. Serendipitous synthesis of unusual double-Z-shaped alkyne by Sonogashira and Glaser coupling is also reported. PMID- 26889748 TI - Differential association of STAT3 and HK-II expression in hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma. AB - STAT3 and hexokinase II (HK-II) are involved in viral infection and carcinogenesis of various cancers including hepatocellular carcinoma (HCC). The roles of STAT3 and HK-II in hepatitis B virus (HBV)- and hepatitis C virus (HCV) related HCC remain largely unclear. This study examined STAT3 and HK-II expression in HBV- and HCV-related HCC, HBV-related liver fibrosis, and normal control liver by using tissue microarray and immunohistochemical method. Results showed that STAT3 expression in HBV-related HCC, HCV-related HCC, and HBV-related liver fibrosis was significantly higher than in control liver (P < 0.001, P = 0.016, and P = 0.005, respectively) and had no significant differences between these three diseased liver tissues. The HK-II expression in HBV-related HCC was significantly higher than that in HCV-related HCC, HBV-related liver fibrosis, and control liver (P = 0.007, P = 0.029, and P = 0.008, respectively) but had no significant elevation in and no significant differences between HCV-related HCC, HBV-related liver fibrosis, and control liver. The HK-II expression was significantly correlated to STAT3 expression in HBV-related HCC (P = 0.022), but no correlation was observed in HCV-related HCC, HBV-related liver fibrosis, and control liver. In conclusion, STAT3 expression is upregulated in both HBV- and HCV-related HCC, while HK-II is predominantly upregulated and correlated to STAT3 in HBV-related HCC. These differential expression and association may suggest the distinct roles of STAT3 and HK-II in hepatocarcinogenesis of HBV and HCV infection. Studies are needed to confirm the relationship of STAT3 and HK-II and to examine the underlying mechanisms. J. Med. Virol. 88:1552-1559, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26889747 TI - Inhibition of ice recrystallization and cryoprotective activity of wheat proteins in liver and pancreatic cells. AB - Efficient cryopreservation of cells at ultralow temperatures requires the use of substances that help maintain viability and metabolic functions post-thaw. We are developing new technology where plant proteins are used to substitute the commonly-used, but relatively toxic chemical dimethyl sulfoxide. Recombinant forms of four structurally diverse wheat proteins, TaIRI-2 (ice recrystallization inhibition), TaBAS1 (2-Cys peroxiredoxin), WCS120 (dehydrin), and TaENO (enolase) can efficiently cryopreserve hepatocytes and insulin-secreting INS832/13 cells. This study shows that TaIRI-2 and TaENO are internalized during the freeze-thaw process, while TaBAS1 and WCS120 remain at the extracellular level. Possible antifreeze activity of the four proteins was assessed. The "splat cooling" method for quantifying ice recrystallization inhibition activity (a property that characterizes antifreeze proteins) revealed that TaIRI-2 and TaENO are more potent than TaBAS1 and WCS120. Because of their ability to inhibit ice recrystallization, the wheat recombinant proteins TaIRI-2 and TaENO are promising candidates and could prove useful to improve cryopreservation protocols for hepatocytes and insulin-secreting cells, and possibly other cell types. TaENO does not have typical ice-binding domains, and the TargetFreeze tool did not predict an antifreeze capacity, suggesting the existence of nontypical antifreeze domains. The fact that TaBAS1 is an efficient cryoprotectant but does not show antifreeze activity indicates a different mechanism of action. The cryoprotective properties conferred by WCS120 depend on biochemical properties that remain to be determined. Overall, our results show that the proteins' efficiencies vary between cell types, and confirm that a combination of different protection mechanisms is needed to successfully cryopreserve mammalian cells. PMID- 26889749 TI - Myocardial T1 rho mapping of patients with end-stage renal disease and its comparison with T1 mapping and T2 mapping: A feasibility and reproducibility study. AB - PURPOSE: To evaluate the feasibility of T1 rho mapping in myocardium at 3T and to determine whether T1 rho mapping could better characterize myocardial injury in end-stage renal disease (ESRD) patients compared to T1 and T2 mapping. MATERIALS AND METHODS: T1 rho mapping, T1 mapping, and T2 mapping were performed at 3T on 35 healthy volunteers (15 males, 20 females, 40.7 +/- 13.6 years) and 32 ESRD patients (16 males, 16 females, 48.6 +/- 11.9 years). The mean T1 rho, T1 , and T2 values were compared using Student's t-test and correlated with cardiac function parameters, including peak ejection rate (PER), short-axis percent thickening (SAPT), peak filling rate (PFR), and time to peak filling (TTPF). RESULTS: The mean T1 rho values (49.4 +/- 2.6 msec vs. 52.2 +/- 4.0 msec, P = 0.001) and T2 values (50.5 +/- 2.5 msec vs. 54.1 +/- 4.0 msec, P < 0.001) were significantly different between the volunteers and patients, but there were no significant differences between the two groups in the T1 values (1253.1 +/- 71.6 msec vs. 1273.4 +/- 41.7 msec, P = 0.157). The mean T1 rho values were negatively correlated with the PER (r = -0.397; P = 0.03), SAPT (r = -0.688; P < 0.001), and PFR (r = -0.537; P = 0.002), whereas positively correlated with the TTPF (r = 0.677; P < 0.001). The mean T2 values were negatively correlated only with the SAPT (r = -0.427; P = 0.019) in the ESRD patients. CONCLUSION: T1 rho mapping of the myocardium is feasible at 3T. T1 rho values are higher in ESRD patients and relate to cardiac function, which may better characterize myocardial injury than can T1 and T2 . J. Magn. Reson. Imaging 2016;44:723-731. PMID- 26889751 TI - Assessing atmospheric concentration of polychlorinated biphenyls by evergreen Rhododendron maximum next to a contaminated stream. AB - Conifers are often used as an air passive sampler, but few studies have focused on the implication of broadleaf evergreens to monitor atmospheric semivolatile organic compounds such as polychlorinated biphenyls (PCBs). In the present study, the authors used Rhododendron maximum (rhododendron) growing next to a contaminated stream to assess atmospheric PCB concentrations. The present study area was located in a rural setting and approximately 2 km downstream of a former capacitor plant. Leaves from the same mature shrubs were collected in late fall 2010 and winter and spring 2011. Polychlorinated biphenyls were detected in the collected leaves, suggesting that rhododendron can be used as air passive samplers in rural areas where active sampling is impractical. Estimated SigmaPCB (47 congeners) concentrations in the atmosphere decreased from fall 2010 to spring 2011 with concentration means at 3990 pg m(-3) , 2850 pg m(-3) , and 931 pg m(-3) in fall 2010, winter 2011, and spring 2011, respectively. These results indicate that the atmospheric concentrations at this location continue to be high despite termination of active discharge from the former industrial source. Leaves had a consistent pattern of high concentrations of tetra-CBs and penta-CBs similar to the congener distribution in polyethylene passive samplers deployed in the water column, suggesting that volatilized PCBs from the stream were the primary source of contaminants in rhododendron leaves. Environ Toxicol Chem 2016;35:2192-2198. (c) 2016 SETAC. PMID- 26889750 TI - Changes in dermal matrix in the absence of Rac1 in keratinocytes. AB - Keratinocytes, in response to irritants, secrete pro-inflammatory mediators which recruit and activate immune and mesenchymal cells, including fibroblasts, to repair the skin. Fibroblasts respond by synthesising collagen and promoting the crosslinking extracellular matrix (ECM). We recently showed that the deletion of Rac1 in keratinocytes causes heightened inflammation due to aberrant crosstalk with immune cells. Indeed, the skin of these mice shows a higher inflammatory response to the induction of irritant contact dermatitis (ICD), and also even to treatment with a vehicle alone, compared with controls. As inflammation is intimately linked with fibrotic disease in the skin, this raised the question as to whether this deletion may also affect the deposition and arrangement of the dermal ECM. This study assessed the effects of Rac1 deletion in keratinocytes and of the heightened inflammatory status by induction of ICD on the tissue localisation and arrangements of dermal collagen. Qualitative analysis did not reveal evidence for the formation of pathologies in the dermis. However, quantitative analysis did reveal some perturbations in the dermal matrix, namely that only the combination of the lack of Rac1 and ICD affects the architectural organisation of the dermal collagen, and that a higher inflammatory state in the tissue (i.e. when Rac1 is deleted in the keratinocytes or ICD is induced in the skin, or a combination of both) influences the diameter of the collagen fibrils. It is proposed that this increase in the diameter of collagen fibrils due to inflammation may serve as pre-fibrotic marker enabling earlier determination of fibrosis and earlier treatment. This study has revealed previously unknown effects on the ECM due to the deletion of Rac1 in keratinocytes. PMID- 26889753 TI - The analysis of influence of individual and environmental factors on 2-wheeled users' injuries. AB - OBJECTIVE: Powered 2-wheeled motor vehicles (PTWs) are one of the most vulnerable categories of road users. Bearing that fact in mind, we have researched the effects of individual and environmental factors on the severity and type of injuries of PTW users. The aim was to recognize the circumstances that cause these accidents and take some preventive actions that would improve the level of road safety for PTWs. METHODS: In the period from 2001 to 2010, an analysis of 139 road accidents involving PTWs was made by the Faculty of Transport and Traffic Engineering in Belgrade. The effects of both individual (age, gender, etc.) and environmental factors (place of an accident, time of day, etc.) on the cause of accidents and severity and type of injuries of PTWs are reported in this article. Analyses of these effects were conducted using logistic regression, chi square tests, and Pearson's correlation. RESULTS: Factors such as categories of road users, pavement conditions, place of accident, age, and time of day have a statistically significant effect on PTW injuries, whereas other factors (gender, road type; that is, straight or curvy) do not. The article also defines the interdependence of the occurrence of particular injuries at certain speeds. The results show that if PTW users died of a head injury, these were usually concurrent with chest injuries, injuries to internal organs, and limb injuries. CONCLUSIONS: It has been shown that there is a high degree of influence of individual factors on the occurrence of accidents involving 2-wheelers (PTWs/bicycles) but with no statistically significant relation. Establishing the existence of such conditionalities enables identifying and defining factors that have an impact on the occurrence of traffic accidents involving bicyclists or PTWs. Such a link between individual factors and the occurrence of accidents makes it possible for system managers to take appropriate actions aimed at certain categories of 2-wheelers in order to reduce casualties in a particular area. The analysis showed that most of the road factors do not have a statistically significant effect on either category of 2-wheeler. Namely, the logistic regression analysis showed that there is a statistically significant effect of the place of accident on the occurrence of accidents involving bicyclists. PMID- 26889754 TI - 'People look down on you when you tell them how he died': Qualitative insights into stigma as experienced by suicide survivors. AB - This paper aims to present findings that convey how people felt stigmatized after the loss of a loved one to suicide. A qualitative design was used for the purpose of this study. Data were collected using in-depth, face-to-face interviews. Audio recordings of the interviews were transcribed and thematically analyzed. Ten people bereaved by suicide participated in the study. Four themes emerged from the data namely: Feeling blamed, shamed and judged; Feeling isolated/rejected by friends and community; Feeling silenced and Feeling the burden of others' discomfort. Findings show that stigmatization of the bereaved by suicide had detrimental effects on their relationships and their help seeking behaviours. Further, due to stigma imposed on them by others, participants were denied the opportunity to tell their stories which further complicated their grieving process. Further education and training is required for health professionals to enhance understanding of the specific needs of those bereaved by suicide. PMID- 26889752 TI - Abscisic acid regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin. AB - Understanding the mechanisms regulating root development under drought conditions is an important question for plant biology and world agriculture. We examine the effect of osmotic stress on abscisic acid (ABA), cytokinin and ethylene responses and how they mediate auxin transport, distribution and root growth through effects on PIN proteins. We integrate experimental data to construct hormonal crosstalk networks to formulate a systems view of root growth regulation by multiple hormones. Experimental analysis shows: that ABA-dependent and ABA independent stress responses increase under osmotic stress, but cytokinin responses are only slightly reduced; inhibition of root growth under osmotic stress does not require ethylene signalling, but auxin can rescue root growth and meristem size; osmotic stress modulates auxin transporter levels and localization, reducing root auxin concentrations; PIN1 levels are reduced under stress in an ABA-dependent manner, overriding ethylene effects; and the interplay among ABA, ethylene, cytokinin and auxin is tissue-specific, as evidenced by differential responses of PIN1 and PIN2 to osmotic stress. Combining experimental analysis with network construction reveals that ABA regulates root growth under osmotic stress conditions via an interacting hormonal network with cytokinin, ethylene and auxin. PMID- 26889755 TI - Comparison of outcome of patients with CLL who are referred or nonreferred to a specialized CLL clinic: a Canadian population-based study. AB - Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) patients in Manitoba are either referred to the CLL Clinic at CancerCare Manitoba (CCMB) or are followed by other hematologists and general practitioners. However, it has been unclear whether referral to the CLL clinic influences patient outcome. Overall survival (OS) was assessed for all CLL/SLL patients diagnosed in Manitoba between 2007 and 2011. Of 555 patients, 281 (51%) were referred to the CLL clinic. Patients seen in this clinic had a twofold increased OS compared to patients who were managed by other hematologists and general practitioners (HR 2.375, P 0.0002) when adjusted for age, gender, presence of pre- or post-CLL cancer, treatment and urban/rural location. In the nonreferred population there was a striking correlation between advancing age and decreasing OS. However, this correlation was almost eliminated in the referred population who were more likely to receive chemotherapy. Patients referred and seen in the CLL clinic have an improved OS compared to nonreferred patients and this appears to be primarily related to improved OS in the elderly. Possible explanations for this finding are discussed. PMID- 26889758 TI - Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes. AB - The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter. PMID- 26889759 TI - Does patent protection for personalized medicine still exist in the USA? PMID- 26889757 TI - Bioinspired Alkenyl Amino Alcohol Ionizable Lipid Materials for Highly Potent In Vivo mRNA Delivery. AB - Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve nucleic acid delivery in vivo. PMID- 26889756 TI - Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases. AB - The regioselective condensations of various 7-hydroxyisoflavonoids with bis(N,N dimethylamino)methane in a Mannich reaction provided C-8 N,N-dimethylaminomethyl substituted isoflavonoids in good yield. Similar condensations of 7-hydroxy-8 methylisoflavonoids led to the C-6-substituted analogs. Thermal eliminations of dimethylamine from these C-6 or C-8 N,N-dimethylaminomethyl-substituted isoflavonoids generated ortho-quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho-quinone methide intermediates trapped dienophiles including 2,3 dihydrofuran, 3,4-dihydro-2H-pyran, 3-(N,N-dimethylamino)-5,5-dimethyl-2 cyclohexen-1-one, 1-morpholinocyclopentene, and 1-morpholinocyclohexene to give various inverse electron-demand Diels-Alder adducts. Several adducts derived from 8-N,N-dimethylaminomethyl-substituted isoflavonoids displayed good activity in the 1-10 MUm concentration range in an in vitro proliferation assay using the PC 3 prostate cancer cell line. PMID- 26889760 TI - Color polymorphs of aldose reductase inhibitor epalrestat: configurational, conformational and synthon differences. AB - We report five crystalline polymorphs and an amorphous phase of epalrestat together with configurational isomerism and color behavior: form I (deep red), form II (deep orange), form III (bright yellow), form IV (yellow), and form V (orange) are in the E,Z configuration of the drug, and a Z,Z isomer (bright yellow). Two pathways are identified for polymorph conversion: direct transformation of the E,Z isomer and another pathway via the Z,Z isomer to the E,Z polymorphs. From a pharmaceutical perspective, the stability of polymorphs was established under grinding, solvent slurry and thermal conditions: form I (thermodynamic) > form II > form V > form III > form IV (least stable). PMID- 26889761 TI - Analysis of HIV models with two time delays. AB - Time delays can affect the dynamics of HIV infection predicted by mathematical models. In this paper, we studied two mathematical models each with two time delays. In the first model with HIV latency, one delay is the time between viral entry into a cell and the establishment of HIV latency, and the other delay is the time between cell infection and viral production. We defined the basic reproductive number and showed the local and global stability of the steady states. Numerical simulations were performed to evaluate the influence of time delays on the dynamics. In the second model with HIV immune response, one delay is the time between cell infection and viral production, and the other delay is the time needed for the adaptive immune response to emerge to control viral replication. With two positive delays, we obtained the stability crossing curves for the model, which were shown to be a series of open-ended curves. PMID- 26889762 TI - Measurement of extracellular vesicles and other submicron size particles by flow cytometry. PMID- 26889765 TI - Proton Transport in a Highly Conductive Porous Zirconium-Based Metal-Organic Framework: Molecular Insight. AB - The water stable UiO-66(Zr)-(CO2H)2 MOF exhibits a superprotonic conductivity of 2.3*10(-3) S cm(-1) at 90 degrees C and 95 % relative humidity. Quasi-elastic neutron scattering measurements combined with aMS-EVB3 molecular dynamics simulations were able to probe individually the dynamics of both confined protons and water molecules and to further reveal that the proton transport is assisted by the formation of a hydrogen-bonded water network that spans from the tetrahedral to the octahedral cages of this MOF. This is the first joint experimental/modeling study that unambiguously elucidates the proton-conduction mechanism at the molecular level in a highly conductive MOF. PMID- 26889764 TI - Practitioner perspectives on extended clinical placement programs in optometry. AB - BACKGROUND: Some universities are looking to provide a more diverse range of clinical learning experiences through extended clinical placement programs. This approach will potentially have a significant impact on practitioners. The aim of this study was to conduct a national survey of optometrists to ascertain their perspectives on participating in extended clinical placement programs. METHODS: Members of Optometry Australia were invited to participate in a survey conducted during June and July 2014. RESULTS: A total of 268 practitioners participated (six per cent of registered Australian optometrists): 159 were predominantly employees or locums and 109 were owners or managers who identified as the key representative of a practice or organisation for the purpose of this survey. Almost two-thirds (65 per cent) of participants, who were employees or locums were supportive of extended clinical placement programs. Among this group, females were more likely to be supportive than males (p = 0.033). In comparison, just over one-third (34 per cent) of participants who were key decision-makers were supportive, with 30 per cent possibly supportive and 36 per cent not supportive. Among key decision-makers, males were more likely to be supportive (p = 0.009). The top three perceived advantages of supervising a student were: opportunity to mentor early career development, opportunity to give back to the profession and future recruitment. The top three perceived disadvantages were: burden on time, decrease in number of patients examined and burden on support staff. Suggested incentives for supervising students were credit for continuing professional development and financial remuneration. CONCLUSION: There appears to be moderate support for extended clinical placement programs; however, there are incentives that might engage a larger proportion of the profession in the future. These findings can inform the development of effective and sustainable clinical training programs for optometry students. Additionally, the findings might be used as evidence to seek Government support for clinical placement training in optometry. PMID- 26889766 TI - Moving Toward a Field of Palliative Psychology. PMID- 26889767 TI - ECDC expert opinion on efficacy and effectiveness of neuraminidase inhibitors published for public consultation. PMID- 26889768 TI - Attacker Deterrence and Perceived Risk in a Stackelberg Security Game. AB - In Stackelberg security games, a defender must allocate scarce resources to defend against a potential attacker. The optimal defense involves the randomization of scarce security resources, yet how attackers perceive the risk given randomized defense is not well understood. We conducted an experiment where attackers chose whether to attack or not attack targets protected by randomized defense schemes, the key treatment variable being whether the defender picks one target at random to guard or imperfectly guards all targets. The two schemes are expected-payoff equivalent, and when provided separately we found no effect of having one scheme or the other. Yet, when both are present, we found that subjects had a preference for the fixed scheme, a preference that cannot be reduced to differences in beliefs. Overall, our results suggest that understanding how individuals perceive risk is vital to understand the behavior of attackers. PMID- 26889763 TI - Safety, tolerability and pharmacokinetic properties of coadministered azithromycin and piperaquine in pregnant Papua New Guinean women. AB - AIMS: The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of coadministered azithromycin (AZI) and piperaquine (PQ) for treating malaria in pregnant Papua New Guinean women. METHODS: Thirty pregnant women (median age 22 years; 16-32 weeks' gestation) were given three daily doses of 1 g AZI plus 960 mg PQ tetraphosphate with detailed monitoring/blood sampling over 42 days. Plasma AZI and PQ were assayed using liquid chromatography-mass spectrometry and high-performance liquid chromatography, respectively. Pharmacokinetic analysis was by population-based compartmental models. RESULTS: The treatment was well tolerated. The median (interquartile range) increase in the rate-corrected electrocardiographic QT interval 4 h postdose [12 (6-26) ms(0) (.5) ] was similar to that found in previous studies of AZI given in pregnancy with other partner drugs. Six women with asymptomatic malaria cleared their parasitaemias within 72 h. Two apararasitaemic women developed late uncomplicated Plasmodium falciparum infections on Days 42 and 83. Compared with previous pregnancy studies, the area under the concentration-time curve (AUC0-infinity ) for PQ [38818 (24354-52299) MUg h l(-1) ] was similar to published values but there was a 52% increase in relative bioavailability with each dose. The AUC0-infinity for AZI [46799 (43526 49462) MUg h l(-1) ] was at least as high as reported for higher-dose regimens, suggesting saturable absorption and/or concentration-dependent tissue uptake and clearance from the central compartment. CONCLUSIONS: AZI-PQ appears to be well tolerated and safe in pregnancy. Based on the present/other data, total AZI doses higher than 3 g for the treatment and prevention of malaria may be unnecessary in pregnant women, while clearance of parasitaemia could improve the relative bioavailability of PQ. PMID- 26889769 TI - Cannabis effects on driving longitudinal control with and without alcohol. AB - Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive ?(9) -tetrahydrocannabinol (THC) blood concentrations. Current occasional (>=1*/last 3 months, <=3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889770 TI - l-carnitine protects human hepatocytes from oxidative stress-induced toxicity through Akt-mediated activation of Nrf2 signaling pathway. AB - In our previous study, l-carnitine was shown to have cytoprotective effect against hydrogen peroxide (H2O2)-induced injury in human normal HL7702 hepatocytes. The aim of this study was to investigate whether the protective effect of l-carnitine was associated with the nuclear factor erythroid 2 (NFE2) related factor 2 (Nrf2) pathway. Our results showed that pretreatment with l carnitine augmented Nrf2 nuclear translocation, DNA binding activity and heme oxygenase-1 (HO-1) expression in H2O2-treated HL7702 cells, although l-carnitine treatment alone had no effect on them. Analysis using Nrf2 siRNA demonstrated that Nrf2 activation was involved in l-carnitine-induced HO-1 expression. In addition, l-carnitine-mediated protection against H2O2 toxicity was abrogated by Nrf2 siRNA, indicating the important role of Nrf2 in l-carnitine-induced cytoprotection. Further experiments revealed that l-carnitine pretreatment enhanced the phosphorylation of Akt in H2O2-treated cells. Blocking Akt pathway with inhibitor partly abrogated the protective effect of l-carnitine. Moreover, our finding demonstrated that the induction of Nrf2 translocation and HO-1 expression by l-carnitine directly correlated with the Akt pathway because Akt inhibitor showed inhibitory effects on the Nrf2 translocation and HO-1 expression. Altogether, these results demonstrate that l-carnitine protects HL7702 cells against H2O2-induced cell damage through Akt-mediated activation of Nrf2 signaling pathway. PMID- 26889772 TI - Adverse Outcome Pathway (AOP) Informed Modeling of Aquatic Toxicology: QSARs, Read-Across, and Interspecies Verification of Modes of Action. AB - Alternative approaches have been promoted to reduce the number of vertebrate and invertebrate animals required for the assessment of the potential of compounds to cause harm to the aquatic environment. A key philosophy in the development of alternatives is a greater understanding of the relevant adverse outcome pathway (AOP). One alternative method is the fish embryo toxicity (FET) assay. Although the trends in potency have been shown to be equivalent in embryo and adult assays, a detailed mechanistic analysis of the toxicity data has yet to be performed; such analysis is vital for a full understanding of the AOP. The research presented herein used an updated implementation of the Verhaar scheme to categorize compounds into AOP-informed categories. These were then used in mechanistic (quantitative) structure-activity relationship ((Q)SAR) analysis to show that the descriptors governing the distinct mechanisms of acute fish toxicity are capable of modeling data from the FET assay. The results show that compounds do appear to exhibit the same mechanisms of toxicity across life stages. Thus, this mechanistic analysis supports the argument that the FET assay is a suitable alternative testing strategy for the specified mechanisms and that understanding the AOPs is useful for toxicity prediction across test systems. PMID- 26889771 TI - The diffusive way out: Herpesviruses remodel the host nucleus, enabling capsids to access the inner nuclear membrane. AB - Herpesviruses are large DNA viruses that utilize the host nucleus for genome replication as well as capsid assembly. After maturation, these 125 nm large capsid assemblies must cross the nucleoplasm to engage the nuclear envelope and bud into the cytoplasm. Here we summarize our recent findings how this motility is facilitated. We suggest that herpesvirus induced nuclear remodeling allows capsids to move by diffusion in the nucleus and not by motor-dependent transport. PMID- 26889773 TI - Clam Ruditapes philippinarum recovery from short-term exposure to the combined effect of salinity shifts and Arsenic contamination. AB - The current study assessed the biochemical alterations induced in the clam species Ruditapes philippinarum after exposure to salinity shifts (14, 28 and 42) and arsenic (As) contamination (0 and 2mg/L). The capacity of this species to recover (96h and 28 days) after exposure (96h) to both stressors, acting alone and in combination, was also evaluated. After exposure, regardless of the salinity tested, clams contaminated with As showed higher concentrations than non contaminated specimens. After recovery, As concentration in clams decreased, with contaminated and non-contaminated specimens presenting similar values. The results obtained further demonstrated that exposure to As (2mg/L) at different salinities (salinities 14, 28 and 42) and salinity 42 (As 0mg/L) lead to an increase of lipid peroxidation and detoxification mechanisms in clams, compared with non-contaminated clams at salinities of 14 and 28. After recovery, at salinities 14 and 28, clams previously exposed to As were capable to decrease their oxidative stress to levels found in non-contaminated clams. Nevertheless, at salinity 42 both contaminated and non-contaminated clams did not survive. Overall results of measured energy-related parameters, indicators of oxidative stress, antioxidant and biotransformation enzymes indicated that As exposure and salinity shifts caused biochemical alterations in R. philippinarum, with stronger impacts when both stressors were acting in combination. PMID- 26889774 TI - Involvement of Drug Transporters in Organ Toxicity: The Fundamental Basis of Drug Discovery and Development. AB - Membrane transporters play a pivotal role in many organs to maintain their normal physiological functions and contribute significantly to drug absorption, distribution, and elimination. Knowledge gained from gene modified animal models or human genetic disorders has demonstrated that interruption of the transporter activity can lead to debilitating diseases or organ toxicities. Herein we describe transporter associated diseases and organ toxicities resulting from transporter gene deficiency or functional inhibition in the liver, kidney, gastrointestinal tract (GIT), and central nervous system (CNS). While proposing additional transporters as targets for drug-induced organ toxicity, strategies and future perspectives are discussed for transporter risk assessment in drug discovery and development. PMID- 26889775 TI - "Collaborative-ready" students: Exploring factors that influence collaboration during a longitudinal interprofessional education practice experience. AB - A goal of interprofessional education (IPE) is to prepare "collaborative-ready" healthcare professionals to ultimately improve health outcomes. The objective of our study was to explore student-reported factors that influence collaboration within our longitudinal IPE experience. Twenty-five first-year pharmacy students and 50 first-year medical students enrolled in IPE courses were invited to participate in three focus groups. Focus group responses were audio-recorded, transcribed verbatim, and applied to a qualitative thematic analysis. Eighteen students participated with six students in each group. Compared to the medical students, the pharmacy students were younger (22 vs. 26 years), had earned only a high school diploma, and had less healthcare experience. Emergent themes that students reported revealed various factors that can facilitate and inhibit collaboration among student participants. These findings can inform curricular redesign to focus on: clarifying provider roles, requiring ongoing preceptor development, enhancing course orientation, and coordinating student schedules to better prepare "collaborative-ready" students. PMID- 26889776 TI - Fabrication of an integrated cartilage/bone joint prosthesis and its potential application in joint replacement. AB - An integrated cartilage/bone joint prosthesis was designed and fabricated using a two-step molding injection method, in which ethylene-vinyl acetate copolymer (EVA) was used as the upper cartilage layer, and hydroxyapatite/polyamide66 (HA/PA66) composites as the underlying bone layer. Holes punched in the underlying layer improved the interfacial bonding strength between the two layers by means of the mechanical interlocking obviously. Then, the physicochemical properties and in vivo behaviors of the integrated joint prosthesis were investigated. The results showed that the upper layer displayed good bio tribological properties which were suitable for the articular cartilage replacement, while the underlying layer demonstrated good mechanical performance, excellent biocompatibility and high bioactivity, and could accelerate bone regeneration and the early bio-fixation of the prosthesis. Therefore, the prosthesis prepared here will have a wide prospect to be used in joint replacement. PMID- 26889777 TI - A Au(I)-Precatalyst with a Cyclopropenium Counterion: An Unusual Ion Pair. AB - The synthesis and X-ray crystal structure of a novel Au(I)-precatalyst applied to intermolecular alkyne hydroamination is reported. Density functional theory (DFT) calculations revealed the cyclopropenium counterion of this Au(I)-precatalyst imparts stability through H-bonding and other noncovalent interactions. PMID- 26889778 TI - Clinical profile and outcome of refractory convulsive status epilepticus in older children from a developing country. AB - PURPOSE: The current study evaluates the etiology, clinical course and outcome of refractory convulsive status epilepticus (CSE) in older children. METHODS: Retrospective analysis of data of 73 children with CSE, aged >=2 and <=12 years was performed. Odds ratios were calculated between variables for clinical course and outcome. Mortality of the group was analyzed using survival analysis. RESULTS: Thirty three (45.2%) children progressed to refractory status epilepticus (RSE). The most common etiology for CSE was acute symptomatic in 44 (60.3%) of which 37 had presumed CNS infections. The odds of progressing to RSE were higher in children with acute symptomatic etiology (OR 2.62; CI - 95%; 0.99 7.14; p=0.041). Progression to RSE increased the chances of severe sepsis by six times (OR 6.08; CI - 95%; 1.19-31.02; p=0.036) and acidosis by nearly 15 times (OR 14.77; CI - 95%; 1.19-31.02; p=0.020). Overall mortality was 13.7%, higher in RSE (21.2% vs.7.5%). Amongst the 63 surviving children followed for 1 year from discharge, progression to RSE increased the odds of disability by seven times (OR 7.08; CI 29.31; p=0.004). CONCLUSION: Acute symptomatic etiology was the commonest cause of CSE among older children from developing country and increased the odds of progressing to RSE. RSE was significantly associated with disability at 1 year from discharge. PMID- 26889779 TI - Levocarnitine induced seizures in patients on valproic acid: A negative systematic review. AB - OBJECTIVE: Warnings of L-carnitine induced seizures are recorded on product monographs and pharmacy databases, without any referenced literature. This medication can potentially improve the hospital course in those patients with valproic acid (VPA) induced hyperammonemic encephalopathy, but may be withheld because of this warning. The goal was to perform an extensive systematic review of the literature to document the incidence of levocarnitine (L-carnitine) induced seizures in those patients on VPA therapy. METHODS: Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform, clinicaltrials.gov (inception to June 2015), and reference lists of relevant articles were searched. The strength of evidence was to be adjudicated using both the Oxford and GRADE methodology by two independent reviewers. RESULTS: We failed to identify a single study implicating L-carnitine supplementation leading to seizures in any patient on VPA therapy. This contradicts all quoted, but unsubstantiated, concerns on product monographs and pharmacy databases related to seizure induction/propagation with L carnitine supplementation. CONCLUSION: There is no literature available to support claims of L-carnitine induced seizures during supplementation in patients on VPA therapy for seizures. This contradicts quoted, but not referenced, concerns on the product monograph. In patients suffering from hypocarnitinemia or hyperammonemic encephalopathy while on VPA, L-carnitine supplementation can be considered knowing there is no data to support seizure propagation or induction with administration of this supplement. PMID- 26889780 TI - Band-Edge Exciton Fine Structure and Recombination Dynamics in InP/ZnS Colloidal Nanocrystals. AB - We report on a temperature-, time-, and spectrally resolved study of the photoluminescence of type-I InP/ZnS colloidal nanocrystals with varying core size. By studying the exciton recombination dynamics we assess the exciton fine structure in these systems. In addition to the typical bright-dark doublet, the photoluminescence stems from an upper bright state in spite of its large energy splitting (~100 meV). This striking observation results from dramatically lengthened thermalization processes among the fine structure levels and points to optical-phonon bottleneck effects in InP/ZnS nanocrystals. Furthermore, our data show that the radiative recombination of the dark exciton scales linearly with the bright-dark energy splitting for CdSe and InP nanocrystals. This finding strongly suggests a universal dangling bonds-assisted recombination of the dark exciton in colloidal nanostructures. PMID- 26889781 TI - MYC and PVT1 synergize to regulate RSPO1 levels in breast cancer. AB - Copy number gain of the 8q24 region including the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene has been observed in many different cancers and is associated with poor outcomes. While the role of MYC in tumor formation has been clearly delineated, we have recently shown that co-operation between adjacent long non-coding RNA plasmacytoma variant transcription 1 (PVT1) and MYC is necessary for tumor promotion. Chromosome engineered mice containing an increased copy of Myc-Pvt1 (Gain Myc-Pvt1) accelerates mammary tumors in MMTV-Neu mice, while single copy increase of each is not sufficient. In addition, mammary epithelium from the Gain Myc-Pvt1 mouse show precancerous phenotypes, notably increased DNA replication, elevated -H2AX phosphorylation and increased ductal branching. In an attempt to capture the molecular signatures in pre-cancerous cells we utilized RNA sequencing to identify potential targets of supernumerary Myc-Pvt1 cooperation in mammary epithelial cells. In this extra view we show that an extra copy of both Myc and Pvt1 leads to increased levels of Rspo1, a crucial regulator of canonical beta-catenin signaling required for female development. Human breast cancer tumors with high levels of MYC transcript have significantly more PVT1 transcript and RSPO1 transcript than tumors with low levels of MYC showing that the murine results are relevant to a subset of human tumors. Thus, this work identifies a key mechanism in precancerous and cancerous tissue by which a main player in female differentiation is transcriptionally activated by supernumerary MYC and PVT1, leading to increased premalignant features, and ultimately to tumor formation. PMID- 26889782 TI - Exploiting Bacterial Operons To Illuminate Human Iron-Sulfur Proteins. AB - Organisms from all kingdoms of life use iron-sulfur proteins (FeS-Ps) in a multitude of functional processes. We applied a bioinformatics approach to investigate the human portfolio of FeS-Ps. Sixty-one percent of human FeS-Ps bind Fe4S4 clusters, whereas 39% bind Fe2S2 clusters. However, this relative ratio varies significantly depending on the specific cellular compartment. We compared the portfolio of human FeS-Ps to 12 other eukaryotes and to about 700 prokaryotes. The comparative analysis of the organization of the prokaryotic homologues of human FeS-Ps within operons allowed us to reconstruct the human functional networks involving the conserved FeS-Ps common to prokaryotes and eukaryotes. These functional networks have been maintained during evolution and thus presumably represent fundamental cellular processes. The respiratory chain and the ISC machinery for FeS-P biogenesis are the two conserved processes that involve the majority of human FeS-Ps. Purine metabolism is another process including several FeS-Ps, in which BOLA proteins possibly have a regulatory role. The analysis of the co-occurrence of human FeS-Ps with other proteins highlighted numerous links between the iron-sulfur cluster machinery and the response mechanisms to cell damage, from repair to apoptosis. This relationship probably relates to the production of reactive oxygen species within the biogenesis and degradation of FeS-Ps. PMID- 26889784 TI - Synthesis of Oxadiazol-5-imines via the Cyclizative Capture of in Situ Generated Cyanamide Ions and Nitrile Oxides. AB - An unprecedented intermolecular cyclizative capture of the cyanamide anion and several nitrile oxides enables the synthesis of oxadiazol-5-imines. PMID- 26889783 TI - Virgin Olive Oil Enriched with Its Own Phenols or Complemented with Thyme Phenols Improves DNA Protection against Oxidation and Antioxidant Enzyme Activity in Hyperlipidemic Subjects. AB - The effects of virgin olive oil (VOO) enriched with its own phenolic compounds (PC) and/or thyme PC on the protection against oxidative DNA damage and antioxidant endogenous enzymatic system (AEES) were estimated in 33 hyperlipidemic subjects after the consumption of VOO, VOO enriched with its own PC (FVOO), or VOO complemented with thyme PC (FVOOT). Compared to pre intervention, 8-hydroxy-2'-deoxyguanosine (a marker for DNA damage) decreased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in olive and thyme phenolic metabolites. Superoxide dismutase (AEES enzyme) significantly increased in the FVOO intervention and to a greater extent in the FVOOT with a parallel significant increase in thyme phenolic metabolites. When all three oils were compared, FVOOT appeared to have the greatest effect in protecting against oxidative DNA damage and improving AEES. The sustained intake of a FVOOT improves DNA protection against oxidation and AEES probably due to a greater bioavailability of thyme PC in hyperlipidemic subjects. PMID- 26889785 TI - Unique Core-Shell Nanorod Arrays with Polyaniline Deposited into Mesoporous NiCo2O4 Support for High-Performance Supercapacitor Electrodes. AB - Polyaniline (PANI), one of the most attractive conducting polymers for supercapacitors, demonstrates a great potential as high performance pseudocapacitor materials. However, the poor cycle life owing to structural instability remains as the major hurdle for its practical application; hence, making the structure-to-performance design on the PANI-based supercapacitors is highly desirable. In this work, unique core-shell NiCo2O4@PANI nanorod arrays (NRAs) are rationally designed and employed as the electrode material for supercapacitors. With highly porous NiCo2O4 as the conductive core and strain buffer support and nanoscale PANI layer as the electrochemically active component, such a heterostructure achieves favorably high capacitance while maintaining good cycling stability and rate capability. By adopting the optimally uniform and intimate coating of PANI, the fabricated electrode exhibits a high specific capacitance of 901 F g(-1) at 1 A g(-1) in 1 M H2SO4 electrolyte and outstanding capacitance retention of ~91% after 3000 cycles at a high current density of 10 A g(-1), which is superior to the electrochemical performance of most reported PANI-based pseudocapacitors in literature. The enhanced electrochemical performance demonstrates the complementary contributions of both componential structures in the hybrid electrode design. Also, this work propels a new direction of utilizing porous matrix as the highly effective support for polymers toward efficient energy storage. PMID- 26889786 TI - Factors Associated with Loss to Follow-up during Treatment for Multidrug Resistant Tuberculosis, the Philippines, 2012-2014. AB - To identify factors associated with loss to follow-up during treatment for multidrug-resistant (MDR) tuberculosis (TB) in the Philippines, we conducted a case-control study of adult patients who began receiving treatment for rifampin resistant TB during July 1-December 31, 2012. Among 91 case-patients (those lost to follow-up) and 182 control-patients (those who adhered to treatment), independent factors associated with loss to follow-up included patients' higher self-rating of the severity of vomiting as an adverse drug reaction and alcohol abuse. Protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses. These results provide insights for designing interventions aimed at reducing patient loss to follow-up during treatment for MDR TB. PMID- 26889787 TI - Absence of Middle East Respiratory Syndrome Coronavirus in Camelids, Kazakhstan, 2015. PMID- 26889788 TI - Hysteroscopic treatment of Mullerian duct anomalies. AB - Mullerian duct anomalies are a broad and complex spectrum of abnormalities that are often associated with infertility, obstetric complications as well as gynecological disorders among women of reproductive age. Operative hysteroscopy is the gold standard in the treatment of most of those anomalies amenable to surgical correction. The evidence to date shows an ongoing increase in the release of recommendations in favour of operative hysteroscopic treatment, in concert with the progressive refinement of hysteroscopic technologies and techniques. The aim of this paper was to describe and critically evaluate the role of the currently available hysteroscopic techniques for treating Mullerian duct anomalies, taking into account their indications, feasibility and efficacy as well as their impact on the reproductive outcome. Special attention will be paid to the most recently developed minimally invasive treatments for uterine and vaginal anomalies. PMID- 26889789 TI - Borrelia miyamotoi and Candidatus Neoehrlichia mikurensis in Ixodes ricinus Ticks, Romania. PMID- 26889790 TI - Use of the SPARC software program to calculate hydrolysis rate constants for the polymeric brominated flame retardants BC-58 and FR-1025. AB - The SPARC software program was used to estimate the acid-catalyzed, neutral, and base-catalyzed hydrolysis rate constants for the polymeric brominated flame retardants BC-58 and FR-1025. Relatively rapid hydrolysis of BC-58, producing 2,4,6-tribromophenol-and ultimately tetrabromobisphenol A-as the hydrolytically stable end products from all potential hydrolysis reactions, is expected in both environmental and biological systems with starting material hydrolytic half-lives (t(1/2,hydr)) ranging from less than 1 h in marine systems, several hours in cellular environments, and up to several weeks in slightly acid fresh waters. Hydrolysis of FR-1025 to give 2,3,4,5,6-pentabromobenzyl alcohol is expected to be slower (t(1/2,hydr) less than 0.5 years in marine systems up to several years in fresh waters) than BC-58, but is also expected to occur at rates that will contribute significantly to environmental and in vivo loadings of this compound. PMID- 26889792 TI - Factors influencing the desire to provide MS patient care in clinical practice among physiatrists. AB - BACKGROUND: Rehabilitation care is an important part of care for individuals with multiple sclerosis (MS). Little is known about factors influencing physiatrists' desire to provide MS care. OBJECTIVE: This study examines factors associated with physiatrists' attitudes towards providing MS care. METHODS: We collaborated with the American Academy of Physical Medicine and Rehabilitation to survey a sample of 300 U.S. physiatrists. Analyses examined the association of exposure to MS care resources during residency, physician demographic and practice characteristics with attitudes toward providing MS care. RESULTS: Physiatrists indicating negative factors limiting the number of MS patients seen in clinical practice were more likely to practice in a setting other than a major city and less likely to have interacted with MS specialists during residency. Physiatrists indicating factors having a positive influence on providing MS patient care were more likely to practice within a major city, see one or more MS patients per week, and serve as the primary physiatrist directing care for one or more MS patients. CONCLUSIONS: Physiatrists indicated positive and negative attitudes towards MS care. Increasing exposure to MS patients, providing resources for MS care, and participating in continuing education on MS, may encourage physiatrists to provide MS patient care. PMID- 26889791 TI - Glucocorticoids accelerate maturation of the heme pathway in fetal liver through effects on transcription and DNA methylation. AB - Glucocorticoids are widely used in threatened preterm labor to promote maturation in many organ systems in preterm babies and have significant beneficial effects on morbidity and mortality. We performed transcriptional profiling in fetal liver in a rat model of prenatal glucocorticoid exposure and identified marked gene expression changes in heme biosynthesis, utilization, and degradation pathways in late gestation. These changes in gene expression associated with alterations in DNA methylation and with a reduction in hepatic heme concentration. There were no persistent differences in gene expression, DNA methylation, or heme concentrations at 4 weeks of age, suggesting that these are transient effects. Our findings are consistent with glucocorticoid-induced accelerated maturation of the haematopoietic system and support the hypothesis that glucocorticoids can drive changes in gene expression in association with alterations in DNA methylation. PMID- 26889793 TI - Utilization of the Expanded Disability Status Scale as a distinctive instrument for walking impairment in persons with multiple sclerosis with mild disability. AB - BACKGROUND: The Expanded Disability Status Scale (EDSS) is a well-established clinical measure to assess disability in multiple sclerosis (MS). Gait dysfunction is primarily considered for scoring only above EDSS 3.5. However, the changes in functional systems in below EDSS 3.5 may result gait disturbances. OBJECTIVE: To determine the distinctive ability of the EDSS 2.0 in terms of walking impairment as well as fatigue, depression, and quality of life in persons with MS with mild disability. METHODS: All participants underwent the neurological examination for generating an EDSS score and completed the measures of walking performance, as well as other measures of fatigue, depression, and quality of life. The participants were divided into two groups according to the EDSS scores (i.e. EDSS <2.0 and 2.0-3.5). RESULTS: Participants with EDSS 2.0-3.5 had significantly worse walking performance, as well as fatigue, depression, and quality of life levels than the participants with EDSS <2.0 (p < 0.05). The EDSS significantly correlated with the measures of walking performance, as well as other measures of fatigue, depression, and quality of life. CONCLUSIONS: The EDSS 2.0 has a distinctive ability in terms of walking impairment as well as fatigue, depression, and quality of life. PMID- 26889794 TI - Non-invasive brain stimulation and robot-assisted gait training after incomplete spinal cord injury: A randomized pilot study. AB - BACKGROUND: Locomotor training with a robot-assisted gait orthosis (LT-RGO) and transcranial direct current stimulation (tDCS) are interventions that can significantly enhance motor performance after spinal cord injury (SCI). No studies have investigated whether combining these interventions enhances lower extremity motor function following SCI. OBJECTIVE: Determine whether active tDCS paired with LT-RGO improves lower extremity motor function more than a sham condition, in subjects with motor incomplete SCI. METHODS: Fifteen adults with SCI received 36 sessions of either active (n = 9) or sham (n = 6) tDCS (20 minutes) preceding LT-RGO (1 hour). Outcome measures included manual muscle testing (MMT; primary outcome measure); 6-Minute Walk Test (6MinWT); 10-Meter Walk Test (10MWT); Timed Up and Go Test (TUG); Berg Balance Scale (BBS); and Spinal Cord Independence Measure-III (SCIM-III). RESULTS: MMT showed significant improvements after active tDCS, with the most pronounced improvement in the right lower extremity. 10MWT, 6MinWT, and BBS showed improvement for both groups. TUG and SCIM-III showed improvement only for the sham tDCS group. CONCLUSION: Pairing tDCS with LT-RGO can improve lower extremity motor function more than LT-RGO alone. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living. PMID- 26889795 TI - Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study. AB - STUDY DESIGN: This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). OBJECTIVE: Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. SETTING: University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. METHODS: A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. RESULTS: Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. CONCLUSION: These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. SPONSORSHIP: This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670). PMID- 26889796 TI - Factors influencing acceptance of disability among stroke patients in Tianjin, China:A cross-sectional study. AB - BACKGROUND: Stroke has become the leading cause of acquired disability worldwide. Psychological maladjustment and related reactions for stroke disability has subsequently revealed a negative impact on stroke rehabilitation process. Acceptance of disability (AOD) is widely confirmed as a critical factor for psychosocial regulation and disability acceptance. OBJECTIVE: This study aims to investigate acceptance of disability and its influencing factors among stroke patients in China. METHODS: A total of 220 hospitalized stroke patients were investigated using questionnaire on demographics and disease characters, Adaptation Of Disability Scale-Revised, and other psychological instruments: Medical Coping Modes Questionnaire (MCMQ), Functional Activities Questionnaire (FAQ), Self-Rating Depression Scale (SDS), and Perceived Social Support Scale (PSSS). RESULTS: The mean score of AOD is 74.15 (range 32~128), which reflected a moderate level of disability acceptance among stroke patients in China. Statistical analysis showed that confrontation, the understanding of stroke, self rating depression, ability of functional activities and family support were major factors affecting acceptance of disability among disabled stroke patients, which explained 49.6% of the total variance. CONCLUSIONS: In clinical practice, professionals should identify patients with low levels of disability acceptance and explore effective psychological intervention model on the theoretical foundation of different dimensions in AOD theory and related predictors. PMID- 26889797 TI - Participation in leisure activities after stroke: A survey of community-residing stroke survivors in Nigeria. AB - BACKGROUND: Leisure provides pleasure and relaxation, and has health benefits even after a stressful and life-changing event such as a stroke. OBJECTIVE: This study examined leisure participation among a sample of community-residing stroke survivors in Nigeria. METHODS: Fifty-five stroke survivors undergoing rehabilitation were consecutively recruited from two government hospitals in Northern Nigeria. Data on pre- and post-stroke participation, and socio demographic (age, sex, marital, employment, and educational status) and clinical (level of disability, post-stroke duration, stroke type and side of hemiplegia/hemiparesis) attributes of the stroke survivors were obtained. Leisure participation was assessed in four domains of recreational, social, cognitive, and productive/creative activities. Associations between leisure participation and the socio-demographic and clinical variables were examined using bivariate analysis. RESULTS: Mean (SD) age of the stroke survivors was 53.55 (14.39) years. Prevalence of leisure participation was 89.1%. Participation in specific leisure domains however varied thus: social (83.6%), cognitive (60%), recreational (41.8%), productive/creative activities (30.9%). Significant associations were observed between participation in cognitive, productive/creative, and recreational leisure activities, and specific socio-demographic and clinical attributes. CONCLUSIONS: Leisure participation was high in a general sense but marginal in recreational and productive/creative activities. The observed socio demographic and clinical associations with post-stroke leisure participation may assist in providing effective leisure rehabilitation strategies. PMID- 26889798 TI - Is non-invasive neuromuscular electrical stimulation effective in severe chronic neurogenic dysphagia? Reporton a post-traumatic brain injury patient. AB - BACKGROUND: Neurogenic dysphagia is a difficulty in swallowing induced by nervous system disease. It often causes serious complications, which are preventable if dysphagia is properly managed. There is growing debate concerning the usefulness of non-invasive neuromuscular electrical stimulation (NMES) in treating swallowing dysfunction. OBJECTIVE: Aim of this study was to assess the effectiveness of Vitalstim(c) device, and to investigate the neurophysiological mechanisms underlying functional recovery. METHODS: A 34-year-old man, affected by severe chronic dysphagia following traumatic brain injury, underwent two different intensive rehabilitation trainings, including either conventional rehabilitation alone or coupled to Vitalstim training. We evaluated patient swallowing function in two separate sessions (i.e. before and after the two trainings) by means of ad hoc swallowing function scales and electrophysiological parameters (rapid paired associative stimulation). The overall Vitalstim program was articulated in 6 weekly sessions for 6 weeks. RESULTS: The patient did not report any side-effect either during or following both the intensive rehabilitation trainings. We observed an important improvement in swallowing function only after Vitalstim training. In fact, the patient was eventually able to safely eat even solid food. CONCLUSIONS: This is the first report objectively suggesting (by means of rPAS) a correlation between the brain neuroplastic changes induced by Vitalstim and the swallowing function improvement. It is hypothesizable that Vitalstim may have targeted cortical (and maybe subcortical) brain areas that are recruited during the highly coordinated function of swallowing, and it may have thus potentiated the well-known neuroplastic changes induced by repetitive and intensive swallowing exercises, probably thanks to metaplasticity phenomena. PMID- 26889799 TI - Can Cognitive Behavioral Therapy for Insomnia also treat fatigue, pain, and mood symptoms in individuals with traumatic brain injury? - A multiple case report. AB - BACKGROUND: Individuals with traumatic brain injury (TBI) often develop sleep disorders post-injury. The most common one is insomnia, which can exacerbate other post-injury symptoms, including fatigue, impaired cognition, depression, anxiety, and pain. Cognitive Behavioral Therapy for Insomnia (CBT-I) is a manualized treatment that effectively treats insomnia with secondary effects on cognition, mood, and pain in various populations. OBJECTIVE: This paper reviews the use of CBT-I for three participants with TBI of different severities. METHODS: Pre- and post-treatment assessments of insomnia, fatigue, depression, anxiety, and pain were conducted. Mood was further assessed at follow-up. Minimal clinically important difference (MCID) scores derived from the research literature were used to establish clinically meaningful symptom improvement on self-report questionnaires. RESULTS: The reduction in insomnia severity scores for all three participants were not large enough to be considered a clinically significant improvement following CBT-I, although trends toward improvement were observed. However, all participants showed clinically significant reductions in anxiety at post-treatment; the effects persisted for 2 participants at follow-up. Reductions in depression symptoms were observed for 2 participants at post treatment, and treatment effects persisted for 1 participant at follow-up. One participant endorsed clinically significant improvements in fatigue and pain severity. CONCLUSIONS: We conclude that CBT-I may provide secondary benefits for symptoms commonly experienced by individuals with TBI, especially mood disturbances. PMID- 26889800 TI - Cognitive functioning following traumatic brain injury: A five-year follow-up. AB - OBJECTIVE: To describe the long-term prevalence and severity of cognitive deficits following significant (i.e., ventilation required for >24 hours) traumatic brain injury. To assess a comprehensive range of cognitive functions using psychometric measures with established normative, reliability, and validity data. METHODS: A group of 71 adults was assessed at approximately five years (mean = 66 months) following injury. Assessment of cognitive functioning covered the domains of intelligence, attention, verbal and visual memory, visual-spatial construction, and executive functions. RESULTS: Impairment was evident across all domains but prevalence varied both within and between domains. Across aspects of intelligence clinical impairment ranged from 8-25% , attention 39-62% , verbal memory 16-46% , visual memory 23-51% , visual-spatial construction 38% , and executive functions (verbal fluency) 13% . In addition, 3-23% of performances across the measures were in the borderline range, suggesting a high prevalence of subclinical deficit. CONCLUSIONS: Although the prevalence of impairment may vary across cognitive domains, long-term follow-up documented deficits in all six domains. These findings provide further evidence that while improvement of cognitive functioning following significant traumatic brain injury may be possible, recovery of function is unlikely. PMID- 26889801 TI - Transfer effects of errorless Goal Management Training on cognitive function and quality of life in brain-injured persons. AB - BACKGROUND: Previous findings had shown that the addition of errorless learning to traditional Goal Management Training (GMT) resulted in superior results when training everyday tasks in persons with executive deficits after brain injury. OBJECTIVE: To investigate the additional effects of an errorless GMT on cognitive function and quality of life after acquired brain injury. METHODS: This is a supplementary analysis of findings from an RCT in which 67 patients with executive impairments after acquired brain injury were randomly allocated to an experimental errorless GMT (n = 33) or conventional GMT (n = 34) to train two individually chosen everyday tasks. Objective cognitive function using neuropsychological tests, subjective cognitive complaints and quality of life using questionnaires were assessed before and after training. RESULTS: No significant interaction effects between these three types of outcome measures and the two forms of GMT were found. Irrespective of treatment, performance on two executive tests (Modified Six Elements Test; p = 0.006, Zoo Map test; p = 0.001) improved and daily executive function problems as reported by the participants (EFI; p = 0.001) and proxies (DEX; p = 0.01) diminished. CONCLUSIONS: Besides the previously found superiority of errorless GMT when training everyday tasks, additional improvements in cognition and quality of life did not differ between the two treatments. PMID- 26889802 TI - Swallowing in primary progressive aphasia. AB - BACKGROUND: Few studies have described characteristics of swallowing in primary progressive aphasia (PPA) and its variants. OBJECTIVE: To describe and characterize swallowing and eating behaviors of patients with PPA, as well as their correlates with neuropsychiatric symptoms and patterns of communication. METHODS: We studied 16 patients with PPA and 16 their caregivers. PPA was subdivided in agrammatic variant (PPA-G), semantic variant (PPA-S) and logopenic variant (PPA-L). All patients and their caregivers were screened with the following scales: "Assessment of Feeding and Swallowing Difficulties in Dementia", "Neuropsychiatric Inventory", and "Functional Outcome Questionnaire for Aphasia". RESULTS: Patients with PPA-S had diverse swallowing problems such as drooling of saliva or food, multiple swallows, delayed swallow and choking, all of which correlated with anxiety, apathy and aberrant motor behavior. Patients with PPA-G and PPA-L had choking and delayed swallow, respectively. Disturbances in eating behaviors were more frequent in the group with PPA-L, and they correlated with difficulties in patterns of communication. CONCLUSIONS: All variants showed swallowing difficulties and they were more frequent in PPA-S. Further studies with larger samples of patients are needed to better characterize swallowing problems and their consequences in the different variants of PPA. PMID- 26889803 TI - Using reliability of change analysis to evaluate post-acute neuro-rehabilitation. AB - BACKGROUND: It is important to evaluate change in order to re-assure commissioners, staff and patients of the effectiveness of interventions, but also in order to identify areas for improvement. OBJECTIVE: To consider whether analysis of improvement at the level of the individual, taking into account measurement error, may offer a further valuable way to assess change and inform service development over considering change at the group level in a post-acute neuro-rehabilitation unit. METHOD: Pre and post intervention Scores on the FIM+FAM Full Scale and Cognitive and Motor subscales were considered for eighteen patients aged between 35 and 81 with mixed diagnoses who attended a post-acute inpatient neuro-rehabilitation unit for treatment. RESULTS: Statistically significant improvements were achieved on the FIM+FAM Full Scale and Cognitive and Motor subscales in a whole group analysis. Reliable change analyses for each patient within each subscale however identified only half of the sample achieved reliable improvement within the Motor domain and just one person within the Cognitive domain (5.6%). CONCLUSIONS: Findings are consistent with the emphasis of the rehabilitation unit on physical/motor function, and unsurprising as many of those assessed had multiple sclerosis, an often deteriorative condition. Use of reliable change analysis allowed a more detailed understanding of intervention impact, potentially identifying what services reliably work for whom, thereby informing future planning. PMID- 26889804 TI - Surgical Placement of Catheters for Long-term Cardiovascular Exercise Testing in Swine. AB - This protocol describes the surgical procedure to chronically instrument swine and the procedure to exercise swine on a motor-driven treadmill. Early cardiopulmonary dysfunction is difficult to diagnose, particularly in animal models, as cardiopulmonary function is often measured invasively, requiring anesthesia. As many anesthetic agents are cardiodepressive, subtle changes in cardiovascular function may be masked. In contrast, chronic instrumentation allows for measurement of cardiopulmonary function in the awake state, so that measurements can be obtained under quiet resting conditions, without the effects of anesthesia and acute surgical trauma. Furthermore, when animals are properly trained, measurements can also be obtained during graded treadmill exercise. Flow probes are placed around the aorta or pulmonary artery for measurement of cardiac output and around the left anterior descending coronary artery for measurement of coronary blood flow. Fluid-filled catheters are implanted in the aorta, pulmonary artery, left atrium, left ventricle and right ventricle for pressure measurement and blood sampling. In addition, a 20 G catheter is positioned in the anterior interventricular vein to allow coronary venous blood sampling. After a week of recovery, swine are placed on a motor-driven treadmill, the catheters are connected to pressure and flow meters, and swine are subjected to a five-stage progressive exercise protocol, with each stage lasting 3 min. Hemodynamic signals are continuously recorded and blood samples are taken during the last 30 sec of each exercise stage. The major advantage of studying chronically instrumented animals is that it allows serial assessment of cardiopulmonary function, not only at rest but also during physical stress such as exercise. Moreover, cardiopulmonary function can be assessed repeatedly during disease development and during chronic treatment, thereby increasing statistical power and hence limiting the number of animals required for a study. PMID- 26889805 TI - Zebrafish Reel in Phenotypic Suppressors of Autism. AB - Chemical genetics can help decipher novel pathways underlying neurodevelopmental psychiatric impairments. Hoffman et al. (2016) utilized behavioral profiling of psychoactive compounds in zebrafish and identified estrogens as suppressors of a phenotype resulting from loss of an autism risk gene. PMID- 26889806 TI - Parkinson's Disease: A Thalamostriatal Rebalancing Act? AB - Motor impairments in Parkinson's disease are thought to result from hypoactivation of striatal projection neurons in the direct pathway. In this issue of Neuron, Parker et al. (2016) report that dopamine depletion selectively weakens thalamic but not cortical afferents onto these neurons, implicating the thalamus as playing a key role in Parkinsonian motor symptoms. PMID- 26889807 TI - Four to Foxtrot: How Visual Motion Is Computed in the Fly Brain. AB - In this issue of Neuron, Serbe et al. (2016) use cell-type-specific genetic tools to record and manipulate all major inputs to directionally selective neurons in Drosophila. Their results localize the site of motion computation and reveal unexpected complexity of temporal tuning in the underlying neural circuit. PMID- 26889808 TI - The Ying and Yang of Auditory Nerve Damage. AB - Chambers et al. investigate consequences in the central auditory system after profound cochlear denervation. They observed gains in firing rate in auditory cortex despite nearly absent auditory nerve and brainstem responses, suggesting an important role of central plasticity and its clinical implications. PMID- 26889811 TI - Membrane Potential Dynamics of CA1 Pyramidal Neurons during Hippocampal Ripples in Awake Mice. AB - Ripples are high-frequency oscillations associated with population bursts in area CA1 of the hippocampus that play a prominent role in theories of memory consolidation. While spiking during ripples has been extensively studied, our understanding of the subthreshold behavior of hippocampal neurons during these events remains incomplete. Here, we combine in vivo whole-cell and multisite extracellular recordings to characterize the membrane potential dynamics of identified CA1 pyramidal neurons during ripples. We find that the subthreshold depolarization during ripples is uncorrelated with the net excitatory input to CA1, while the post-ripple hyperpolarization varies proportionately. This clarifies the circuit mechanism keeping most neurons silent during ripples. On a finer timescale, the phase delay between intracellular and extracellular ripple oscillations varies systematically with membrane potential. Such smoothly varying delays are inconsistent with models of intracellular ripple generation involving perisomatic inhibition alone. Instead, they suggest that ripple-frequency excitation leading inhibition shapes intracellular ripple oscillations. PMID- 26889813 TI - MiR-218 inhibits the tumorgenesis and proliferation of glioma cells by targeting Robo1. AB - BACKGROUND: Malignant glioma is the most common primary brain tumors directly correlated with the high mortality and poor prognosis in clinical practice. MicroRNAs (miRNAs or miRs) influence numerous cancer-relevant processes including cell proliferation, differentiation and metabolism. However, the role of microRNA in malignant glioma is largely unknown. This study aimed to study the role of miR 218, a tumor-suppressive microRNA, in glioma development both in vivo and in vitro. METHODS: The expression level of miR-218, Slit2 and Robo1 was examined by either quantitative (polymerase chain reaction) or western-blotting from both human glioma tissue and glioma cell lines. U87 cells were transfected with miR 218 and then the expression levels of Slit2 and Robo1 were quantified. Cell proliferation was measured both by the in vitro proliferation assay and in vivo graft studies. The luciferase reporter assay was employed to validate the downstream target of miR-218. RESULTS: The expression of miR-218 was lower in glioma cell lines and glioma tissues from the patients with decreased Slit2 and increased Robo1 protein levels. The over-expression of miR-218 inhibited the tumorgenesis and proliferation of glioma cells remarkably. Furthermore, the over expressing miR-218 in glioma cells results in the downregulation of Robo1 and upregulation of Slit2. Using luciferase reporter assays, we found that Robo1 was a direct downstream target of miR-218. CONCLUSION: Over-expression of miR-218 in glioma cells may inhibit the proliferation and tumorigenicity through targeting Robo1, suggesting that miR-218 could be a potential target for developing therapies in treating glioma. PMID- 26889810 TI - Dopamine Does Double Duty in Motivating Cognitive Effort. AB - Cognitive control is subjectively costly, suggesting that engagement is modulated in relationship to incentive state. Dopamine appears to play key roles. In particular, dopamine may mediate cognitive effort by two broad classes of functions: (1) modulating the functional parameters of working memory circuits subserving effortful cognition, and (2) mediating value-learning and decision making about effortful cognitive action. Here, we tie together these two lines of research, proposing how dopamine serves "double duty", translating incentive information into cognitive motivation. PMID- 26889814 TI - Novel SYK gene variations and changes in binding sites of miRs in breast cancer patients. AB - BACKGROUND: Spleen Tyrosine Kinase (SYK) belongs to non-receptor tyrosine Kinase family, which normally expresses in epithelial breast tissues and acts as a tumor suppressor gene. OBJECTIVE: Analysis of mutations in the SYK gene and deregulation of SYK transcripts by miRNA in breast cancer was studied. METHODS: All exons and exon/intron boundaries of SYK gene were amplified and sequenced in blood samples of 207 breast cancer cases and 200 matched controls using PCR single stranded conformational polymorphism method. RESULTS: Sequence analysis revealed 10 novel mutations in breast cancer patients. Among these 6 mutations (Ala 161Pro, His162Tyr, Phe191Tyr, Val 535Gly, Ser 556lIe and Lys536Gln) were found in exonic region and 4 (26249 T>A, 63941 G>A, 63981G>C and 86548T>A) were found in intronic region. All of these mutations are associated with ~ 5 folds (p< 0.0001) increase in breast cancer risk in present study cohort. Regulation of SYK transcripts by miRNA was also analyzed using in silico bioinformatics tools, exon 6's mutation (Phe191Tyr) was found to have altered interaction with miR-873. CONCLUSION: Overall novel mutations in SYK gene and in silico analysis revealed that these mutations are crucial and might be responsible for altered expression of SYK. PMID- 26889812 TI - A Zebrafish Genetic Screen Identifies Neuromedin U as a Regulator of Sleep/Wake States. AB - Neuromodulation of arousal states ensures that an animal appropriately responds to its environment and engages in behaviors necessary for survival. However, the molecular and circuit properties underlying neuromodulation of arousal states such as sleep and wakefulness remain unclear. To tackle this challenge in a systematic and unbiased manner, we performed a genetic overexpression screen to identify genes that affect larval zebrafish arousal. We found that the neuropeptide neuromedin U (Nmu) promotes hyperactivity and inhibits sleep in zebrafish larvae, whereas nmu mutant animals are hypoactive. We show that Nmu induced arousal requires Nmu receptor 2 and signaling via corticotropin releasing hormone (Crh) receptor 1. In contrast to previously proposed models, we find that Nmu does not promote arousal via the hypothalamic-pituitary-adrenal axis, but rather probably acts via brainstem crh-expressing neurons. These results reveal an unexpected functional and anatomical interface between the Nmu system and brainstem arousal systems that represents a novel wake-promoting pathway. PMID- 26889815 TI - Clustering of self-organizing map identifies five distinct medulloblastoma subgroups. AB - BACKGROUND: Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. OBJECTIVE: Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. METHODS: Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. RESULTS: The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. CONCLUSIONS: Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples. PMID- 26889809 TI - DREADDs for Neuroscientists. AB - To understand brain function, it is essential that we discover how cellular signaling specifies normal and pathological brain function. In this regard, chemogenetic technologies represent valuable platforms for manipulating neuronal and non-neuronal signal transduction in a cell-type-specific fashion in freely moving animals. Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are now commonly used by neuroscientists to identify the circuitry and cellular signals that specify behavior, perceptions, emotions, innate drives, and motor functions in species ranging from flies to nonhuman primates. Here I provide a primer on DREADDs highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward. PMID- 26889816 TI - MiR-155 expression level changes might be associated with initial phases of breast cancer pathogenesis and lymph-node metastasis. AB - BACKGROUND: Breast carcinoma is heterogeneous disease. Understanding the process of invasion and metastasis and the selection of the therapy for patients with breast carcinomas still remains difficult. MicroRNAs are powerful gene expression regulators. Because of inconsistent findings, we have analyzed potential difference in miR-155 levels in three breast cancer groups. OBJECTIVES: Our goals were to examine miR-155 expression levels in normal tissue, non-invasive and invasive breast carcinomas, and their association with standard clinical and pathological parameters and oncomiR-21, and to investigate the ability of miR-155 to separate invasive breast carcinomas with non-invasive component from pure invasive. METHODS: In the group of 40 breast tissue samples, relative expression levels of miR-155 were examined with stem-loop quantitative real-time PCR using TaqMan technology. RESULTS: The significant difference among four examined groups of the breast tissue was detected (p = 0.001). In the group of pure invasive tumors, patients with positive nodal status had significantly higher miR-155 levels (p = 0.046). CONCLUSION: Our results suggest that miR-155 might be involved in breast cancer pathogenesis and in tumor spreading to the lymph nodes, and that it might be used as biomarker for additional stratification of patients with invasive breast carcinomas with non-invasive component. PMID- 26889817 TI - Musculoskeletal Injury in Professional Dancers: Prevalence and Associated Factors: An International Cross-Sectional Study. AB - OBJECTIVE: The purpose of the study was to determine the prevalence and factors associated with injury in professional ballet and modern dancers, and assess if dancers are reporting their injuries and explore reasons for not reporting injuries. DESIGN: Cross-sectional study. SETTING: Participants were recruited from nine professional ballet and modern dance companies in Canada, Denmark, Israel, and Sweden. PARTICIPANTS: Professional ballet and modern dancers. INDEPENDENT VARIABLES: Sociodemographic variables included age, sex, height, weight, and before-tax yearly or monthly income. Dance specific characteristics included number of years in present dance company, number of years dancing professionally, number of years dancing total, and rank in the company. MAIN OUTCOME MEASURES: Self-reported injury and Self-Estimated Functional Inability because of Pain. RESULTS: A total of 260 dancers participated in the study with an overall response rate of 81%. The point prevalence of self-reported injury in professional ballet and modern dancers was 54.8% (95% CI, 47.7-62.1) and 46.3% (95% CI, 35.5-57.1), respectively. Number of years dancing professionally (OR = 4.4, 95% CI, 1.6-12.3) and rank (OR = 2.4, 95% CI, 1.2-4.8) were associated with injury in ballet dancers. More than 15% of all injured dancers had not reported their injury and their reasons for not reporting injury varied. CONCLUSIONS: The prevalence of injury is high in professional dancers with a significant percentage not reporting their injuries for a variety of reasons. Number of years dancing and rank are associated with injury in professional ballet dancers. PMID- 26889819 TI - Cigarette Smoking and Pterygium: A Propensity Score Matching Analysis. AB - PURPOSE: To assess the association between smoking and pterygium among elderly adults by applying a propensity score matching (PSM) approach and to examine a potential dose-response relationship. METHODS: The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years or older in China. Anterior segment examination was performed without pupil dilation using a slitlamp. Pterygium was defined as a raised fleshy triangular fibrovascular tissue growth of the conjunctiva encroaching onto the clear cornea. Information regarding smoking history was collected via a structured interviewer administered questionnaire. The propensity scores for myopia were formulated using seven potential confounders. We matched the propensity scores for smokers and nonsmokers within a caliper of 0.01 of logit function of propensity scores. RESULTS: Slitlamp examination was successfully performed in 4567 adults. The odds ratio of pterygium for cigarette smoking before matching was 0.65 (95% confidence interval, 0.56 to 0.75; p < 0.001). There were significant covariate imbalances between comparison groups, and after PSM, covariate imbalances were significantly reduced. After PSM, the magnitude of association was slightly reduced (odds ratio, 0.70; 95% confidence interval, 0.55 to 0.89; p = 0.004). Adults with more daily cigarette consumption were less likely to be affected by pterygium in multivariate analysis (p for trend = 0.02). CONCLUSIONS: Smokers were less likely to be affected by pterygium. The PSM approach may be a useful method to address selection bias in observational studies when randomized trials cannot ethically be conducted. PMID- 26889820 TI - New Perspective on Myopia Control with Orthokeratology. AB - PURPOSE: To compare peripheral refraction along both the horizontal and vertical retinal meridians before and after orthokeratology (OK) lens wear. METHODS: Nineteen young adult myopic subjects (mean age, 28 +/- 7 years) were fitted with OK lenses in both eyes. Central and peripheral refraction and corneal topography measurements were taken before and after 14 nights of OK. All measurements were taken with no correction or OK lens in place. RESULTS: At baseline before OK, peripheral spherical equivalent refraction (M) across the horizontal meridian did not vary significantly from center. M across the vertical meridian was more myopic than the center (p < 0.05). After OK, there was a significant hyperopic shift in M (p < 0.001); both meridians now experienced myopic peripheral refraction. At baseline, J180 across the horizontal meridian was more negative than the center, and along the vertical meridian, it was more positive than the center (all p < 0.05). At baseline, J45 was more positive than center with increased eccentricity in the temporal and inferior retina and more negative than center with increased eccentricity in the nasal and superior retina. Orthokeratology caused greater rate of change of peripheral J180 across both retinal meridians (p < 0.001). Furthermore, compared with baseline, J45 became more positive in the nasal and superior retina and more negative in the temporal and inferior retina (all p < 0.05). CONCLUSIONS: Orthokeratology lenses induced significant changes in peripheral refraction along the horizontal and vertical meridians. As peripheral myopia was measured at baseline along the vertical meridian, the results of our study suggest that inducing greater degrees of myopic defocus on to the peripheral retina, more than habitually experienced, may be required for effective myopia control. Further investigation into the critical threshold of retinal area receiving myopic defocus and the impact of duration of exposure is necessary to improve the efficacy of current myopia control treatments. PMID- 26889821 TI - Visual Dysfunctions at Different Stages after Blast and Non-blast Mild Traumatic Brain Injury. AB - PURPOSE: To assess the prevalence of visual dysfunctions and associated symptoms in war fighters at different stages after non-blast- or blast-induced mild traumatic brain injury (mTBI). METHODS: A comprehensive retrospective review of the electronic health records of 500 U.S. military personnel with a diagnosis of deployment-related mTBI who received eye care at the Landstuhl Regional Medical Center. For analysis, the data were grouped by mechanism of injury, and each group was further divided in three subgroups based on the number of days between injury and initial eye examination. RESULTS: The data showed a high frequency of visual symptoms and visual dysfunctions. However, the prevalence of visual symptoms and visual dysfunctions did not differ significantly between mechanism of injury and postinjury stage, except for eye pain and diplopia. Among visual symptoms, binocular dysfunctions were more common, including higher near vertical phoria, reduced negative fusional vergence break at near, receded near point of convergence, decreased stereoacuity, and reduced positive relative accommodation. CONCLUSIONS: The lack of difference in terms of visual sequelae between subgroups (blast vs. nonblast) suggests that research addressing the assessment and management of mTBI visual sequelae resulting from civilian nonblast events is relevant to military personnel where combat injury results primarily from a blast event. PMID- 26889822 TI - Choice of Grating Orientation for Evaluation of Peripheral Vision. AB - PURPOSE: Peripheral resolution acuity depends on the orientation of the stimuli. However, it is uncertain if such a meridional effect also exists for peripheral detection tasks because they are affected by optical errors. Knowledge of the quantitative differences in acuity for different grating orientations is crucial for choosing the appropriate stimuli for evaluations of peripheral resolution and detection tasks. We assessed resolution and detection thresholds for different grating orientations in the peripheral visual field. METHODS: Resolution and detection thresholds were evaluated for gratings of four different orientations in eight different visual field meridians in the 20-deg visual field in white light. Detection measurements in monochromatic light (543 nm; bandwidth, 10 nm) were also performed to evaluate the effects of chromatic aberration on the meridional effect. A combination of trial lenses and adaptive optics system was used to correct the monochromatic lower- and higher-order aberrations. RESULTS: For both resolution and detection tasks, gratings parallel to the visual field meridian had better threshold compared with the perpendicular gratings, whereas the two oblique gratings had similar thresholds. The parallel and perpendicular grating acuity differences for resolution and detection tasks were 0.16 logMAR and 0.11 logMAD, respectively. Elimination of chromatic errors did not affect the meridional preference in detection acuity. CONCLUSIONS: Similar to peripheral resolution, detection also shows a meridional effect that appears to have a neural origin. The threshold difference seen for parallel and perpendicular gratings suggests the use of two oblique gratings as stimuli in alternative forced-choice procedures for peripheral vision evaluation to reduce measurement variation. PMID- 26889826 TI - Unified Saliency Detection Model Using Color and Texture Features. AB - Saliency detection attracted attention of many researchers and had become a very active area of research. Recently, many saliency detection models have been proposed and achieved excellent performance in various fields. However, most of these models only consider low-level features. This paper proposes a novel saliency detection model using both color and texture features and incorporating higher-level priors. The SLIC superpixel algorithm is applied to form an over segmentation of the image. Color saliency map and texture saliency map are calculated based on the region contrast method and adaptive weight. Higher-level priors including location prior and color prior are incorporated into the model to achieve a better performance and full resolution saliency map is obtained by using the up-sampling method. Experimental results on three datasets demonstrate that the proposed saliency detection model outperforms the state-of-the-art models. PMID- 26889818 TI - Ipilimumab (Anti-Ctla-4 Mab) in the treatment of metastatic melanoma: Effectiveness and toxicity management. AB - In the last years the onset of new therapies changed the management of malignant melanoma. Anti CTLA-4 antibody ipilimumab was the first drug to achieve a significant improvement in survival of advanced stage melanoma. This new therapeutic agent is characterized by a number of side effects that are totally different from those of traditional chemotherapy, mainly caused by the immune system activation. The purpose of this paper is to underline the central role of ipilimumab in the treatment of metastatic melanoma and to characterize related adverse events in terms of incidence, duration and severity of presentation. The early recognition of these side effects is crucial in order to ensure an appropriate management of the toxicities, thus reducing the long term clinical sequelae and the inappropriate treatment discontinuation. PMID- 26889828 TI - Epidemiological Study of RRT-Treated ESRD in Nanjing - A Ten-Year Experience in Nearly Three Million Insurance Covered Population. AB - BACKGROUND: The growing burden of end-stage renal disease (ESRD) has been a great challenge to the health care system of China. However, the exact epidemiological data for ESRD in China remain unclear. We aimed to investigate the epidemiology of ESRD treated by renal replacement therapy (RRT) in Nanjing based on analysing ten-year data of Nanjing three million insurance covered population. METHODS: Using the electronic registry system of Urban Employee Basic Medical Insurance (UEBMI), we included all subjects insured by UEBMI in Nanjing from 2005 to 2014 and identified subjects who developed ESRD and started RRT in this cohort. RESULTS: The UEBMI population in Nanjing increased from 1,301,882 in 2005 to 2,921,065 in 2014, among which a total of 5,840 subjects developed ESRD and received RRT. Over the 10-year period, the adjusted incidence rates of RRT in the UEBMI cohort gradually decreased from 289.3pmp in 2005 to 218.8pmp in 2014. However, the adjusted prevalence rate increased steadily from 891.7pmp in 2005 to 1,228.6pmp in 2014. The adjusted annual mortality rate decreased from 138.4 per 1000 patient-years in 2005 to 97.8 per 1000 patient-years in 2014. The long-term survival rate fluctuated over the past decade, with the 1-year survival rate ranging from 85.1% to 91.7%, the 3-year survival rate from 69.9% to 78.3% and the 5-year survival rate from 58% to 65.4%. CONCLUSION: Nanjing is facing an increasing burden of ESRD with its improvement of medical reform. The ten-year complete registry data on RRT in urban employees in Nanjing provided a unique opportunity to understand the real threat of ESRD confronting China during its process of health care transition. PMID- 26889827 TI - Proteome Based Construction of the Lymphocyte Function-Associated Antigen 1 (LFA 1) Interactome in Human Dendritic Cells. AB - The beta2-integrin lymphocyte function-associated antigen 1 (LFA-1) plays an important role in the migration, adhesion and intercellular communication of dendritic cells (DCs). During the differentiation of human DCs from monocyte precursors, LFA-1 ligand binding capacity is completely lost, even though its expression levels were remained constant. Yet LFA-1-mediated adhesive capacity on DCs can be regained by exposing DCs to the chemokine CCL21, suggesting a high degree of regulation of LFA-1 activity during the course of DC differentiation. The molecular mechanisms underlying this regulation of LFA-1 function in DCs, however, remain elusive. To get more insight we attempted to identify specific LFA-1 binding partners that may play a role in regulating LFA-1 activity in DCs. We used highly sensitive label free quantitative mass-spectrometry to identify proteins co-immunoprecipitated (co-IP) with LFA-1 from ex vivo generated DCs. Among the potential binding partners we identified not only established components of integrin signalling pathways and cytoskeletal proteins, but also several novel LFA-1 binding partners including CD13, galectin-3, thrombospondin-1 and CD44. Further comparison to the LFA-1 interaction partners in monocytes indicated that DC differentiation was accompanied by an overall increase in LFA-1 associated proteins, in particular cytoskeletal, signalling and plasma membrane (PM) proteins. The here presented LFA-1 interactome composed of 78 proteins thus represents a valuable resource of potential regulators of LFA-1 function during the DC lifecycle. PMID- 26889829 TI - Structural Study of Cell Attachment Peptide Derived from Laminin by Molecular Dynamics Simulation. AB - Peptides with cell attachment activity are beneficial component of biomaterials for tissue engineering. Conformational structure is one of the important factors for the biological activities. The EF1 peptide (DYATLQLQEGRLHFMFDLG) derived from laminin promotes cell spreading and cell attachment activity mediated by alpha2beta1 integrin. Although the sequence of the EF2 peptide (DFATVQLRNGFPYFSYDLG) is homologous sequence to that of EF1, EF2 does not promote cell attachment activity. To determine whether there are structural differences between EF1 and EF2, we performed replica exchange molecular dynamics (REMD) simulations and conventional molecular dynamics (MD) simulations. We found that EF1 and EF2 had beta-sheet structure as a secondary structure around the global minimum. However, EF2 had variety of structures around the global minimum compared with EF1 and has easily escaped from the bottom of free energy. The structural fluctuation of the EF1 is smaller than that of the EF2. The structural variation of EF2 is related to these differences in the structural fluctuation and the number of the hydrogen bonds (H-bonds). From the analysis of H-bonds in the beta-sheet, the number of H-bonds in EF1 is larger than that in EF2 in the time scale of the conventional MD simulation, suggesting that the formation of H bonds is related to the differences in the structural fluctuation between EF1 and EF2. From the analysis of other non-covalent interactions in the amino acid sequences of EF1 and EF2, EF1 has three pairs of residues with hydrophobic interaction, and EF2 has two pairs. These results indicate that several non covalent interactions are important for structural stabilization. Consequently, the structure of EF1 is stabilized by H-bonds and pairs of hydrophobic amino acids in the terminals. Hence, we propose that non-covalent interactions around N terminal and C-terminal of the peptides are crucial for maintaining the beta sheet structure of the peptides. PMID- 26889831 TI - Therapeutic vaccines for prostate cancer: recent advances and future directions. AB - In recent years, therapeutic cancer vaccines have emerged as a viable and promising treatment for prostate cancer. Beyond sipuleucel-T, phase III trials are evaluating multiple vaccine platforms in men with this disease. Growing data evaluating vaccine therapies suggests that these agents are more effective in patients with more indolent and possibly also earlier stages of disease. In addition, a wealth of preclinical data has shown that traditional prostate cancer treatments including anti androgens, cytotoxic and radiation therapies may provide immunologic synergy when given in combination with vaccine platforms. Building off this data, numerous clinical trials are evaluating therapeutic cancer vaccines in early stage prostate cancer and also in combination with traditional prostate cancer therapies. In addition, in order to optimize immune responses, ongoing trials are evaluating vaccines in combination with immune checkpoint inhibitors. Preliminary data from these trials have been promising and are offering an exciting glimpse at the future of immunotherapy for this disease. PMID- 26889834 TI - Temperature-dependent luminescence properties of lanthanide(III) beta-diketonate complex-doped LAPONITE(r). AB - In this work, by doping the lanthanide(III)-hexafluoroacetylacetone complex into LAPONITE(r), we obtained a lanthanide-based organic-inorganic hybrid material. The resulting hybrid materials were fully characterized with elementary analysis, scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD) techniques. The Ln(3+) and HFA loadings were experimentally determined to be roughly 0.3 per u.c. and 0.72 per u.c. by analyzing the supernatant (titration against EDTA) and elemental analysis, respectively. XRD patterns suggest that at least partial complexes are intercalated within the interlayers of the LAPONITE(r). The in situ formation of luminescent Ln(3+) complexes is confirmed by the luminescence data. Furthermore, the emission intensity ratio of the (5)D4 >(7)F5 transition (Tb(3+)) to the (5)D0->(7)F2 transition (Eu(3+)) of the hybrid material containing both Eu(3+) and Tb(3+) can be linearly related to temperature in the range from 197 K to 287 K (temperature sensitivity: 1.107% per K), which will be an appealing alternative for in situ and real time detection of temperature in many special areas. This strategy presents new opportunities for the development of highly sensitive and stable thermo sensors. PMID- 26889832 TI - Road traffic accidents and self-reported Portuguese car driver's attitudes, behaviors, and opinions: Are they related? AB - OBJECTIVE: This study aims to characterize Portuguese car drivers in terms of demographic characteristics, driving experience, and attitudes, opinions, and behaviors concerning road traffic safety. Furthermore, associations between these characteristics and self-reported involvement in a road traffic accident as a driver in the last 3 years were analyzed. A final goal was to develop a final predictive model of the risk of suffering a road traffic accident. METHODS: A cross-sectional analytic study was developed, based on a convenience sample of 612 car drivers. A questionnaire was applied by trained interviewers, embracing various topics related to road safety such as driving under the influence of alcohol or drugs, phone use while driving, speeding, use of advanced driver assistance systems, and the transport infrastructure and environment (European Project SARTRE 4, Portuguese version). From the 52 initial questions, 19 variables were selected through principal component analysis. Then, and in addition to the usual descriptive measures, logistic binary regression models were used in order to describe associations and to develop a predictive model of being involved in a road traffic accident. RESULTS: Of the 612 car drivers, 37.3% (228) reported being involved in a road traffic accident with damage or injury in the past 3 years. In this group, the majority were male, older than 65, with no children, not employed, and living in an urban area. In the multivariate model, several factors were identified: being widowed (vs. single; odds ratio [OR] = 3.478, 95% confidence interval [95% CI], 1.159-10.434); living in a suburban area (vs. a rural area; OR = 5.023, 95% CI, 2.260-11.166); having been checked for alcohol once in the last 3 years (vs. not checked; OR = 3.124, 95% CI, 2.040 4,783); and seldom drinking an energetic beverage such as coffee when tired (vs. always do; OR = 6.822, 95% CI, 2.619-17.769) all suffered a higher risk of being involved in a car accident. CONCLUSIONS: The results obtained with regard to behavioral factors meet the majority of the risk factors associated with car accidents referred to in the literature. This study highlights the relation of relatively minor accidents (the majority with no injuries) with an urban (or semi urban) context and involving older drivers. These accidents are not usually the focus of road safety literature (mainly death and serious health loss) but, in addition to the economic costs involved, they can have a huge impact on road safety (e.g., pedestrian). Specifically, the following interventions can be proposed: more detailed clinical examinations to identify real competencies to drive especially in older drivers (active aging can constitute a new challenge in road safety and new paradigms can arise) and education campaigns on how to cope with fatigue. Future studies in large samples and not based on self-reported behaviors should be developed. PMID- 26889833 TI - Extracellular Matrix Deposition in Engineered Micromass Cartilage Pellet Cultures: Measurements and Modelling. AB - This article explores possible mechanisms governing extracellular matrix deposition in engineered cartilaginous cell pellets. A theoretical investigation is carried out alongside an experimental study measuring proteoglycan and collagen volume fractions within murine chondrogenic (ATDC-5) cell pellets. The simple mathematical model, which adopts a nutrient-dependent proteoglycan production rate, successfully reproduces the periphery-dominated proteoglycan deposition, characteristic of the growth pattern observed experimentally within pellets after 21 days of culture. The results suggest that this inhomogeneous proteoglycan production is due to nutrient deficiencies at the pellet centre. Our model analysis further indicates that a spatially uniform distribution of proteoglycan matrix could be maintained by initiating the culture process with a smaller-sized pellet. Finally, possible extensions are put forward with an aim to improve the model predictions for the early behaviour, where different mechanisms appear to dominate the matrix production within the pellets. PMID- 26889830 TI - A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5'-3' Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe. AB - Epigenetic gene silencing plays a critical role in regulating gene expression and contributes to organismal development and cell fate acquisition in eukaryotes. In fission yeast, Schizosaccharomyces pombe, heterochromatin-associated gene silencing is known to be mediated by RNA processing pathways including RNA interference (RNAi) and a 3'-5' exoribonuclease complex, the exosome. Here, we report a new RNA-processing pathway that contributes to epigenetic gene silencing and assembly of heterochromatin mediated by 5'-3' exoribonuclease Dhp1/Rat1/Xrn2. Dhp1 mutation causes defective gene silencing both at peri-centromeric regions and at the silent mating type locus. Intriguingly, mutation in either of the two well-characterized Dhp1-interacting proteins, the Din1 pyrophosphohydrolase or the Rhn1 transcription termination factor, does not result in silencing defects at the main heterochromatic regions. We demonstrate that Dhp1 interacts with heterochromatic factors and is essential in the sequential steps of establishing silencing in a manner independent of both RNAi and the exosome. Genomic and genetic analyses suggest that Dhp1 is involved in post-transcriptional silencing of repetitive regions through its RNA processing activity. The results describe the unexpected role of Dhp1/Rat1/Xrn2 in chromatin-based silencing and elucidate how various RNA-processing pathways, acting together or independently, contribute to epigenetic regulation of the eukaryotic genome. PMID- 26889835 TI - mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of gammadeltaT17 Development and TCRgamma/delta Recombination. AB - Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity. Although thymic epithelial cells (TECs) are crucial for thymopoiesis and T cell generation, how TEC development and function are controlled is poorly understood. We report here that mTOR complex 1 (mTORC1) in TECs plays critical roles in thymopoiesis and thymus function. Acute deletion of mTORC1 in adult mice caused severe thymic involution. TEC-specific deficiency of mTORC1 (mTORC1KO) impaired TEC maturation and function such as decreased expression of thymotropic chemokines, decreased medullary TEC to cortical TEC ratios, and altered thymic architecture, leading to severe thymic atrophy, reduced recruitment of early thymic progenitors, and impaired development of virtually all T-cell lineages. Strikingly, temporal control of IL-17-producing gammadeltaT (gammadeltaT17) cell differentiation and TCRVgamma/delta recombination in fetal thymus is lost in mTORC1KO thymus, leading to elevated gammadeltaT17 differentiation and rearranging of fetal specific TCRVgamma/delta in adulthood. Thus, mTORC1 is central for TEC development/function and establishment of thymic environment for proper T cell development, and modulating mTORC1 activity can be a strategy for preventing thymic involution/atrophy. PMID- 26889836 TI - Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study. AB - OBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality. DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality. SETTING: Cardiovascular Health Study. PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 +/- 4.7, 40% male, 83% white). MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality. RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 +/- 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52% were prefrail, and 13% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38% (95% confidence interval (CI) = 17-62%) higher odds of frailty than of nonfrailty and 16% (95% CI = 3-30%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95% CI = 1.10-1.23) and frailty (HR = 1.82, 95% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other. CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes. PMID- 26889837 TI - Association Between Anthropometric Measures and Long-Term Survival in Frail Older Women: Observations from the Women's Health Initiative Study. AB - OBJECTIVES: To evaluate the association between currently recommended guidelines and commonly used clinical criteria for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) and all-cause mortality in frail older women. DESIGN: Longitudinal prospective cohort study. SETTING: Women's Health Initiative (WHI)-Observational Study. PARTICIPANTS: A sample of women aged 65-84 with complete data to characterize frailty in the third year of WHI follow up (N = 11,070). MEASUREMENTS: Frailty phenotype was determined using the modified Fried criteria. Information on anthropometric measures (BMI, WC, WHR) was collected in clinical examinations. Cox proportional hazards models were used to estimate the effect of BMI, WC, and WHR on mortality adjusted for demographic characteristics and health behaviors. RESULTS: Over a mean follow-up of 11.5 years, there were 2,911 (26%) deaths in the sample. Women with a BMI from 25.0 to 29.9 kg/m(2) (hazard rate ratio (HR) = 0.80, 95% confidence interval (CI) = 0.73 0.88) and those with a BMI from 30.0 to 34.9 kg/m(2) (HR = 0.79, 95% CI = 0.71 0.88) had lower mortality than those with a BMI from 18.5 to 24.9 kg/m(2) . Women with a WHR greater than 0.8 had higher mortality (HR = 1.16, 95% CI = 1.07-1.26) than those with a WHR of 0.8 or less. No difference in mortality was observed according to WC. Stratifying according to chronic morbidity or smoking status or excluding women with early death and unintentional weight loss did not substantially change these findings. CONCLUSION: In frail, older women, having a BMI between 25.0 and 34.9 kg/m(2) or a WHR of 0.8 or less was associated with lower mortality. Currently recommended healthy BMI guidelines should be reevaluated for frail older women. PMID- 26889838 TI - Frailty Trajectories in an Elderly Population-Based Cohort. AB - OBJECTIVES: To identify distinct frailty trajectories (clusters of individuals following a similar progression of frailty over time) in an aging population and to estimate associations between frailty trajectories and emergency department visits, hospitalizations, and all-cause mortality. DESIGN: Population-based cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Olmsted County, Minnesota residents aged 60-89 in 2005. MEASUREMENTS: Longitudinal changes in frailty between 2005 and 2012 were measured by constructing a yearly Rockwood frailty index incorporating body mass index, 17 comorbidities, and 14 activities of daily living. The frailty index measures variation in health status as the proportion of deficits present of the 32 considered (range 0-1). RESULTS: Of the 16,443 Olmsted County residents aged 60-89 in 2005, 12,270 (74.6%) had at least 3 years of frailty index measures and were retained for analysis. The median baseline frailty index increased with age (0.11 for 60-69, 0.14 for 70-79, 0.19 for 80-89). Three distinct frailty trajectories were identified in individuals aged 60-69 at baseline and two trajectories in those aged 70-79 and 80-89. Within each decade of age, increasing frailty trajectories were associated with greater risks of emergency department visits, hospitalization, and all-cause mortality, even after adjustment for baseline frailty index. CONCLUSION: The number of frailty trajectories differed according to age. Within each age group, those in the highest frailty trajectory had greater healthcare use and worse survival. Frailty trajectories may offer a way to target aging individuals at high risk of hospitalization or death for therapeutic or preventive interventions. PMID- 26889839 TI - Antipsychotic Use in Hospitalized Adults: Rates, Indications, and Predictors. AB - OBJECTIVES: To investigate patterns and predictors of use of antipsychotics in hospitalized adults. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PARTICIPANTS: Individuals aged 18 and older hospitalized from August 2012 to August 2013, excluding those admitted to obstetrics and gynecology or psychiatry or with a psychotic disorder. MEASUREMENTS: Use was ascertained from pharmacy charges. Potentially excessive dosing was defined using guidelines for long-term care facilities. A review of 100 records was performed to determine reasons for use. RESULTS: The cohort included 17,775 admissions with a median age 64; individuals could have been admitted more than once during the study period. Antipsychotics were used in 9%, 55% of which were initiations. The most common reasons for initiation were delirium (53%) and probable delirium (12%). Potentially excessive dosing occurred in 16% of admissions exposed to an antipsychotic. Of admissions with antipsychotic initiation, 26% were discharged on these medications. Characteristics associated with initiation included age 75 and older (relative risk (RR) = 1.4, 95% confidence interval (CI) = 1.2-1.7), male sex (RR = 1.2, 95% CI = 1.1-1.4), black race (RR = 0.8, 95% CI = 0.6-0.96), delirium (RR = 4.8, 95% CI = 4.2-5.7), dementia (RR = 2.1, 95% CI = 1.7-2.6), admission to a medical service (RR = 1.2, 95% CI = 1.1-1.4), intensive care unit stay (RR = 2.1, 95% CI = 1.8-2.4), and mechanical ventilation (RR = 2.0, 95% CI = 1.7-2.4). In individuals who were initiated on an antipsychotic, characteristics associated with discharge on antipsychotics were age 75 and older (RR = 0.6, 95% CI = 0.4-0.7), discharge to any location other than home (RR = 2.5, 95% CI = 1.8 3.3), and class of in-hospital antipsychotic exposure (RR = 1.6, 95% CI = 1.1-2.3 for atypical vs typical; RR = 2.7, 95% CI = 1.9-3.8 for both vs typical). CONCLUSION: Antipsychotic initiation and use were common during hospitalization, most often for delirium, and individuals were frequently discharged on these medications. Several predictors of use on discharge were identified, suggesting potential targets for decision support tools that would be used to prompt consideration of ongoing necessity. PMID- 26889842 TI - Beyond Enrollment: Providing the Highest-Quality Care within Hospice. PMID- 26889840 TI - Global Sensory Impairment in Older Adults in the United States. AB - OBJECTIVES: To determine whether there may be a common mechanism resulting in global sensory impairment of the five classical senses (vision, smell, hearing, touch, and taste) in older adults. DESIGN: Representative, population-based study. SETTING: National Social Life, Health, and Aging Project. PARTICIPANTS: Community-dwelling U.S. adults aged 57 to 85. MEASUREMENTS: The frequency with which impairment co-occurred across the five senses was estimated as an integrated measure of sensory aging. It was hypothesized that multisensory deficits would be common and reflect global sensory impairment that would largely explain the effects of age, sex, and race on sensory dysfunction. RESULTS: Two thirds of subjects had two or more sensory deficits, 27% had just one, and 6% had none. Seventy-four percent had impairment in taste, 70% in touch, 22% in smell, 20% in corrected vision, and 18% in corrected hearing. Older adults, men, African Americans, and Hispanics had greater multisensory impairment (all P < .01). Global sensory impairment largely accounted for the effects of age, sex, and race on the likelihood of impairment in each of the five senses. CONCLUSION: Multisensory impairment is prevalent in older U.S. adults. These data support the concept of a common process that underlies sensory aging across the five senses. Clinicians assessing individuals with a sensory deficit should consider further evaluation for additional co-occurring sensory deficits. PMID- 26889841 TI - Transitions Between Healthcare Settings of Hospice Enrollees at the End of Life. AB - OBJECTIVES: To characterize the number and types of care transitions in the last 6 months of life of individuals who used hospice and to examine factors associated with having multiple transitions in care. DESIGN: Retrospective cohort study. SETTING: One hundred percent fee-for-service Medicare decedent claims data. PARTICIPANTS: Medicare beneficiaries aged 66 and older who died between July 1, 2011, and December 31, 2011, and were enrolled in hospice at some time during the last 6 months of life. MEASUREMENTS: Hierarchical generalized linear modeling was used to identify individual, hospice, and regional factors associated with transitions. The sequence of transitions across healthcare settings was described. Healthcare transitions after hospice enrollment included from and to the hospital, skilled nursing facility, home health agency program, hospice, or home without receiving any service in these four healthcare settings. RESULTS: Of 311,090 hospice decedents, 31,675 (10.2%) had at least one transition after hospice enrollment, and this varied substantially across the United States; 6.6% of all decedents had more than one transition in care after hospice enrollment (range 2-19 transitions). Of hospice users with transitions, 53.4% were admitted to hospitals, 17.7% were admitted to skilled nursing facilities, 9.6% used home health agencies, and 25.8% had transitions to home without receiving the services from the healthcare settings examined. In adjusted analyses, decedents who were younger, nonwhite, enrolled in a for-profit or small hospice program, or had less access to hospital-based palliative care had significantly higher odds of having at least one transition. CONCLUSION: A notable proportion of hospice users experience at least one transition in care in the last 6 months of life, suggesting that further research on the effect of transitions on users and families is warranted. PMID- 26889845 TI - Evolving Demand for Critical Care Services for Elderly Adults with Dementia in Texas: A Population-Based Study. PMID- 26889844 TI - Anticholinergic Medication Use and Risk of Pneumonia in Elderly Adults: A Nested Case-Control Study. AB - OBJECTIVES: To examine the risk of community-acquired pneumonia (CAP) associated with the use of anticholinergic medications in elderly adults. DESIGN: Nested case-control study. SETTING: A regional Medicare Advantage healthcare plan (2009 2010). PARTICIPANTS: Participants were Medicare Advantage Plan enrollees aged 65 and older with at least one inpatient and one outpatient claim with no history of CAP between January 1 and June 30, 2009. Cases were identified as enrollees with an incident diagnosis of CAP, between July 1, 2009, and December 31, 2010 (n = 291). Four age- and sex-matched controls (n = 1,164) were identified per case using incidence density sampling. MEASUREMENTS: Anticholinergic prescription 30 days preceding the event date was the primary exposure. Anticholinergic exposure was defined based on the Anticholinergic Drug Scale (ADS). A conditional logistic regression model stratified on matched case-control sets was used, with exposure to a Level 1, 2, or 3 anticholinergic on the ADS as the main independent variable; CAP as the main outcome variable; and risk factors for CAP as additional explanatory variables. RESULTS: After controlling for risk factors, overall use of anticholinergic medications was significantly associated with risk of pneumonia (odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.20-2.28). The risk of pneumonia remained significant across the different exposure periods, although use of higher-level (ADS Level 2 or 3) anticholinergics was not associated with pneumonia risk (OR = 1.16, 95% CI = 0.70-1.96). CONCLUSION: Overall use of anticholinergic medications, but not higher-level drugs, was associated with greater risk of CAP compared to no use after controlling for other factors. More research is needed to better understand the role of potent anticholinergic medications on pneumonia risk in elderly adults. PMID- 26889843 TI - Elder-Clowning in Long-Term Dementia Care: Results of a Pilot Study. AB - OBJECTIVES: To assess the effects of elder-clowning on moderate to severe behavioral and psychological symptoms of dementia (BPSD) in nursing home residents with dementia, primarily of the Alzheimer's type. DESIGN: Before-and after study. SETTING: Nursing home. PARTICIPANTS: Nursing home residents with moderate to severe BPSD, as defined according to a Neuropsychiatric Inventory Nursing Home version (NPI-NH) score of 10 or greater (N = 23), and their care aides. INTERVENTION: A pair of elder-clowns visited all residents twice weekly (~10 minutes per visit) for 12 weeks. They used improvisation, humor, empathy, and expressive modalities such as song, musical instruments, and dance to individualize resident engagement. MEASUREMENTS: Primary outcomes were BPSD measured using the the NPI-NH, quality of life measured using Dementia Care Mapping (DCM), and nursing burden of care measured using the Modified Nursing Care Assessment Scale (M-NCAS). Secondary outcomes were occupational disruptiveness measured using the NPI-NH, agitation measured using the Cohen Mansfield Agitation Inventory (CMAI), and psychiatric medication use. RESULTS: Over 12 weeks, NPI-NH scores declined significantly (t22 = -2.68, P = .01), and DCM quality-of-life scores improved significantly (F1,50 = 23.09, P < .001). CMAI agitation scores decreased nominally, but the difference was not statistically significant (t22 = -1.86, P = .07). Occupational disruptiveness score significantly improved (t22 = -2.58, P = .02), but there was no appreciable change in M-NCAS scores of staff burden of care. CONCLUSION: Results suggest that elder-clowning reduced moderate to severe BPSD of nursing home residents with dementia, primarily of the Alzheimer's type. Elder-clowning is a promising intervention that may improve Alzheimer's disease care for nursing home residents. PMID- 26889846 TI - Burden of Transitions After Invasive Mechanical Ventilation for U.S. Individuals with Severe Chronic Obstructive Pulmonary Disease: Opportunity to Prepare for Preference-Congruent End-of-Life Care? PMID- 26889847 TI - Influence of Barefoot, Minimalist, and Standard Footwear Conditions on Gait and Balance in Healthy Older Adults. PMID- 26889848 TI - Gait Cost of Using a Mobility Aid in Older Adults with Alzheimer's Disease. PMID- 26889849 TI - Pattern of Emotional Benefits Induced by Regular Singing and Music Listening in Dementia. PMID- 26889850 TI - Comparison of Implantable Cardioverter Defibrillator Therapy and Medical Therapy in Individuals Aged 75 and Older. PMID- 26889851 TI - Sensory Impairments and Cardiovascular Disease Incidence and Mortality in Older British Community-Dwelling Men: A 10-Year Follow-Up Study. PMID- 26889852 TI - Sex-Related Differences in Centenarians and Their Hearts. PMID- 26889853 TI - Radio Surgical Ablation of Acoustic Neuromas: A Unique Treatment Modality for an Elderly Woman. PMID- 26889854 TI - Gallstone Ileus in an Older Nursing Home Resident. PMID- 26889855 TI - When Symptomatic Treatment Becomes Antitumor Treatment for Vipoma: Opportunity for Frail Elderly Adults. PMID- 26889856 TI - Alpha-Fetoprotein Producing Gastric Adenocarcinoma in an Elderly Adult. PMID- 26889857 TI - Fatal Cardiac Arrest Associated with Concomitant Bisoprolol and Verapamil Overdose. PMID- 26889858 TI - Learn from Your Elders: Why We Need to Increase Exposure to Geriatrics in Medical Training. PMID- 26889859 TI - Age Discrimination, Eppur Si Muove (Yet It Moves). PMID- 26889860 TI - The Healthy and Successful Aging of Our Discipline. PMID- 26889861 TI - Study of Factors Associated with Incomplete Bladder Emptying in Older Women. PMID- 26889862 TI - Response to Cosco and Kuh. PMID- 26889863 TI - Response to Sumer and Colleagues. PMID- 26889865 TI - Effect of Multimodal Exercise Program on Physical Function, Falls, and Injuries in Older Women. PMID- 26889864 TI - Response to Aycicek and Colleagues. PMID- 26889867 TI - Erratum. PMID- 26889866 TI - A Macro Role for Microglia in Poststroke Depression. PMID- 26889870 TI - Adhesion modification of neural stem cells induced by nanoscale ripple patterns. AB - We have studied the influence of anisotropic nanopatterns (ripples) on the adhesion and morphology of mouse neural stem cells (C17.2) on glass substrates using cell viability assay, optical microscopy and atomic force microscopy. The ripples were produced by defocused ion beam sputtering with inert Ar ions, which physically remove atoms from the surface at the energy of 800 eV. The ripple periodicity (~200 nm) is comparable to the thickness of the cytoplasmatic microspikes (filopodia) which link the stem cells to the substrate. All methods show that the cell adhesion is significantly lowered compared to the same type of cells on flat glass surfaces. Furthermore, the AFM analysis reveals that the filopodia tend to be trapped parallel or perpendicular to the ripples, which limits the spreading of the stem cell on the rippled substrate. This opens the perspective of controlling the micro-adhesion of stem cells and the orientation of their filopodia by tuning the anisotropic substrate morphology without chemical reactions occurring at the surface. PMID- 26889871 TI - Potential Modulation on Total Internal Reflection Ellipsometry. AB - Electrochemical-total internal reflection ellipsometry (EC-TIRE) has been proposed as a technique to observe the redox reactions on the electrode surface due to its high phase sensitivity to the electrolyte/electrode interface. In this paper, we mainly focus on the influence of the potential modulation on the TIRE response. The analysis suggests that both dielectric constant variation of gold and the electric double layer transformation would modulate the reflection polarization of the surface. For a nonfaradaic process, the signal of TIRE would be proportional to the potential modulation. To testify the analysis, linear sweep voltammetry and open circuit measurement have been performed. The results strongly support the system analysis. PMID- 26889872 TI - Selective attention impairment in amyotrophic lateral sclerosis. AB - Objective of this study was to evaluate attentional control mechanisms in amyotrophic lateral sclerosis (ALS) using an auditory event-related potentials (ERPs) paradigm. Fifteen mild to moderate ALS patients and 15 healthy controls were administered a brief neuropsychological test battery and an ERPs paradigm assessing selective attention. Four types of auditory stimuli were presented in random order: short standard (200 Hz, 200 ms), long standard (200 Hz, 500 ms), short deviant (1000 Hz, 200 ms) and long deviant (1000 Hz, 500 ms). Participants had to respond to the long deviant stimuli only. During the task the electroencephalogram (EEG) was recorded. The N200, P300 and re-orienting negativity (RON) ERP components were analysed. Compared to controls ALS patients showed reduced amplitudes and delayed latencies of N200, P300 and RON. These results could be attributable to both an alteration in change detection resulting in a reduction of the allocation and re-orientation of attentional resources or a general slowing or reduction of neural processing efficiency in the same system. The ERPs results support the hypothesis that ALS involves extramotor cognitive functions including auditory attentional processing at all processing stages, early (200 ms) and late (300-600 ms). These data prove the usefulness and sensitivity of the auditory ERPs in detection of cognitive functions in ALS patients. PMID- 26889873 TI - Significant motor improvement in an infant with congenital heart disease and a rolandic stroke: The impact of early intervention. AB - OBJECTIVE: To report the impact of early motor intervention in an infant with congenital heart disease (CHD) and a stroke. METHODS AND RESULTS: A 35-week newborn with a complex CHD and a normal MRI presented with early motor developmental delay at 2 months. She began an intervention program, which included biweekly motor developmental therapy with a physiotherapist, parental education, and daily home exercises. At 4 months, she underwent cardiac surgery. Following surgery, she was diagnosed with a stroke involving the right sylvian artery territory. She continued her intensive intervention program. The 12-month assessment revealed an evident gain of motor function. Despite MRI evidence of a chronic infarct involving the primary motor cortex, the child had normal motor functions. CONCLUSION: This case report supports the positive impact of early intervention in infants with CHD and its potential effect on enhancing neuroplasticity, even in children with cerebro-vascular accidents involving areas of motor function. PMID- 26889874 TI - Patient involvement in the development of patient-reported outcome measures: a scoping review. AB - BACKGROUND: Patient-reported outcome measures (PROMs) measure patients' perspectives on health outcomes and are increasingly used in health care. To capture the patient's perspective, it is essential that patients are involved in PROM development OBJECTIVE: This article reviews in what ways and to what extent patients are involved in PROM development and whether patient involvement has increased over time. SEARCH STRATEGY: Literature was searched in PubMed, EMBASE, MEDLINE and the Cochrane Methodology Register. INCLUSION CRITERIA: Studies were included if they described a new PROM development. DATA EXTRACTION: Basic information and information regarding patient involvement in development phases was recorded. MAIN RESULTS: A total of 189 studies, describing the development of 193 PROMs, were included. Most PROMs were meant for chronic disease patients (n = 59) and measured quality of life (n = 28). In 25.9% of the PROM development studies, no patients were involved. Patients were mostly involved during item development (58.5%), closely followed by testing for comprehensibility (50.8%), while patient involvement in determining which outcome to measure was minimal (10.9%). Some patient involvement took place in the development of most PROMs, but in only 6.7% patients were involved in all aspects of the development. Patient involvement did not increase with time. CONCLUSIONS: Although patient involvement in PROM development is essential to develop valid patient-centred PROMs, patients are not always involved. When patients are involved, their level of involvement varies considerably. These variations suggest that further attention to building and/or disseminating consensus on requirements for patient involvement in PROM development is necessary. PMID- 26889875 TI - Assessment of CASP11 contact-assisted predictions. AB - We present an overview of contact-assisted predictions in the eleventh round of critical assessment of protein structure prediction (CASP11), which included four categories: predicted contacts (Tp), correct contacts (Tc), simulated sparse NMR contacts (Ts), and cross-linking contacts (Tx). Comparison of assisted to unassisted model quality highlighted a relatively poor overall performance in CASP11 using predicted Tp and crosslinked Tx contact information. However, average model quality significantly improved in the correct Tc and simulated NMR Ts categories for most targets, where maximum improvement of unassisted models reached an impressive 70 GDT_TS. Comparison of the performance in the correct Tc category to CASP10 suggested the improvement in CASP11 model quality originated from an increased number of provided contacts per target. Group rankings based on a combination of scores used in the CASP11 free modeling (FM) assessment for each category highlight four top-performing groups, with three from the Lee lab and one from the Baker lab. We used the overall performance of these groups in each category to develop hypotheses for their relative outperformance in the correct Tc and simulated NMR Ts categories, which stemmed from the fraction of correct contacts provided (correct Tc category) and a reduced fraction of correct contacts offset by an increased coverage of the correct contacts (simulated NMR Ts category). Proteins 2016; 84(Suppl 1):164-180. (c) 2016 Wiley Periodicals, Inc. PMID- 26889876 TI - Comparison of fetal cartilage-derived progenitor cells isolated at different developmental stages in a rat model. AB - Fetal cartilage-derived progenitor cells (FCPCs) could be a useful cell source in cell-based therapies for cartilage disorders. However, their characteristics can vary depending on the developmental stages. The aim of this study was to compare the characteristics of rat FCPCs from the hind limb on embryonic day 14 (E14), E16 and E20 regarding proliferation, pluripotency, and differentiation. Morphologically, rat fetal cartilage tissue showed an increase in cartilaginous differentiation features (Safranin-O, type II collagen) and decrease in pluripotency marker (Sox2) in the order of E14, E16 and E20. E14 FCPCs showed significantly higher doubling time compared to E16 and E20 FCPCs. While the E14 FCPCs expressed pluripotent genes (Sox2, Oct4, Nanog), the E16 and E20 FCPCs expressed chondrogenic markers (Sox9, Col2a1, Acan). E20 FCPCs showed the highest ability to both chondrogenic and adipogenic differentiation and E14 FCPCs showed relatively better activity in osteogenic differentiation. Further analysis showed that E20 FCPCs expressed both adipogenic (C/ebpbeta) and osteogenic (Runx2, Sp7, Taz) transcription factors as well as chondrogenic transcription factors. Our results show an inverse relationship overall between the expression of pluripotency genes and that of chondrogenic and lineage-specific genes in FCPCs under development. Due to its exceptional proliferation and chondrogenic differentiation ability, fetal cells from epiphyseal cartilage (E20 in rats) may be a suitable cell source for cartilage regeneration. PMID- 26889877 TI - A rare case of leiomyosarcoma localized in the Bartholin's gland area and review of the literature. AB - Sarcomas of the vulva in the Bartholin's gland area are extremely rare in adults and only a few cases have been reported in the literature. A 65-year-old female patient without any previous complaint presented to our hospital complaining of a genital lump with progressive enlargement over the last six months. Pelvic examination revealed a 6 * 5 cm solid mass lesion with irregular margins localized in the left Bartholin's gland. Preoperative pathology results indicated a benign lesion, which was subsequently totally excised. Histopathological examination of the lesion revealed leiomyosarcoma. When a lesion is localized in the Bartholin's gland area, preoperative biopsy may suggest benign cytology, which can lead to a delay in diagnosis and curative treatment. Total local excision is the first choice for vulvar-complicated masses in the Bartholin's gland area. The present case is the ninth well-documented case reported in the literature. PMID- 26889878 TI - Pathogenesis, Diagnosis and Treatment of Chronic Lymphocytic Leukemia: Exciting Times. PMID- 26889879 TI - Recurrences and Ongoing Complaints of Diverticulitis; Results of a Survey among Gastroenterologists and Surgeons. AB - OBJECTIVE: This study aims to investigate the current opinion of gastroenterologists and surgeons on treatment strategies for patients, with recurrences or ongoing complaints of diverticulitis. BACKGROUND: Treatment of recurrences and ongoing complaints remains a point of debate. No randomized trials have been published yet and guidelines are not uniform in their advice. DESIGN: A web-based survey was conducted among gastroenterologists and GE surgeons. Questions were aimed at the treatment options for recurrent diverticulitis and ongoing complaints. RESULTS: In total, 123 surveys were filled out. The number of patients with recurrent or ongoing diverticulitis who were seen at the outpatient clinic each year was 7 (0-30) and 5 (0-115) respectively. Surgeons see significantly more patients on an annual basis 20 vs. 15% (p = 0.00). Both surgeons and gastroenterologists preferred to treat patients in a conservative manner using pain medication and lifestyle advise (64.4 vs. 54.0, p = 0.27); however, gastroenterologists would treat patients with mesalazine medication, which is significantly more (28%, p = 0.04) than in the surgical group. Surgeons are inclined more towards surgery (31.5%, p = 0.02). CONCLUSIONS: Both surgeons and gastroenterologists prefer to treat recurrent diverticulitis and ongoing complaints in a conservative manner. Quality of life, the risk of complications and the viewpoint of the patient are considered important factors in the decision to resect the affected colon. PMID- 26889880 TI - Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function. AB - OBJECTIVE: This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. METHODS: A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. RESULTS: A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. CONCLUSIONS: Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long term kidney function despite having worse baseline kidney function. PMID- 26889881 TI - First-in-Man Transcervical Surgical Aortic Valve Replacement Using the CoreVista System. AB - OBJECTIVE: This study aimed to evaluate a novel device system for surgical aortic valve replacement (SAVR) using a unique new less invasive access approach. The hypothesis is that SAVR can be performed through a short transverse incision in the neck, similar to that used for transcervical thymectomy avoiding chest disruption. METHODS: A new device system was developed to provide retraction, step-by-step illumination, and on-screen visualization for the new approach. Preliminary feasibility studies were performed in cadavers. Comprehensive risk analysis was performed, and training was implemented in Thiel preserved cadavers. For the first-in-man clinical case, a 63-year-old woman with symptomatic critical aortic stenosis (The Society of Thoracic Surgeons risk, 11%) and heavily calcified aortic valve was selected. A short transverse incision was made in the neck; the device was introduced, and the sternum was elevated; femorofemoral cardiopulmonary bypass was established; substernal dissection was guided by the sequenced illumination, and high-definition visualization was provided by the device, allowing for optimal exposition of the aorta and aortic valve; and a 23 mm Medtronic ENABLE sutureless valve prosthesis was implanted. Procedure success was evaluated according to the standardized composite end point definition of "device success" proposed by the Valve Academic Research Consortium. RESULTS: Access, delivery, and deployment of the valve prosthesis were successful. The correct position and intended performance of the valve were demonstrated (mean gradient, 6 mm Hg; aortic valve area, 2.5 cm) with the absence of moderate or severe prosthetic aortic regurgitation. Only one valve prosthesis was used. CONCLUSIONS: Transcervical SAVR with sutureless valve is feasible using this novel access system. The new approach has potential to offer patients substantially shorter stay and fewer, less serious complications, as has been observed in transcervical thymectomy. Further studies are merited. PMID- 26889882 TI - A Simple Porcine Model of Inducible Sustained Atrial Fibrillation. AB - The surgical management of atrial fibrillation (AF) is an evolving field with a history of testing various lesion sets and ablation technologies. Previous animal models of AF require a chronic intervention to make AF reliably inducible. Our objective was to create an acute, reliable, and reproducible porcine model of sustained AF. To accomplish this, 21 adult domestic pigs underwent median sternotomy. Methods to induce AF were then performed sequentially: manual stimulation, rapid pacing (200 beats per minute), and then rapid pacing of 8 beats with a cycle length of 300 milliseconds, followed by an extra stimulus at decreasing cycle lengths. If AF was not induced, burst pacing was performed at a cycle length of 90 milliseconds for 30 seconds. If AF was still not induced, intravenous neostigmine was administered, and the process was repeated. Atrial fibrillation was considered sustained after 1 minute. Attempts at AF induction were successful in 18 (86%) of 21. Atrial fibrillation was induced during manual stimulation in four (19%), during rapid pacing in five (24%), during burst pacing in five (24%), and after the administration of neostigmine in four (19%). Mean (SD) duration of AF was 3.6 (2.6) minutes. Of the 18, 14 (78%) reverted to sinus rhythm spontaneously and 4 (22%) required an antiarrhythmic. This technique of inducing AF can easily be used to evaluate new technologies and lesion sets without the need for creating a chronic animal model. PMID- 26889883 TI - Single-Incision Video-Assisted Thoracic Surgery for an Extralobar Sequestration in a Child. AB - Uniportal or single-incision video-assisted thoracic surgery (VATS) has been performed successfully in adult patients with different intrathoracic pathologies for years. However, no report in uniportal/single-incision VATS in pediatric patients in the English literature has been published up to date. This may be explained by the limited number of patients and the difficulties in working in very narrow thoracic cavity of babies and children. For these reasons, all the published cases of VATS for extralobar sequestration in infants or children were performed through the three-port approach. We report herein a case of single incision VATS in a child for the resection of an extralobar sequestration. PMID- 26889884 TI - Synthesis of Redshifted Azobenzene Photoswitches by Late-Stage Functionalization. AB - Azobenzenes are versatile photoswitches that can be cycled between their trans- and cis-configuration with light. The wavelengths required for this isomerization are substantially shifted from the UV to the visible range through tetra-ortho chlorination. These halogenated azobenzenes display unique photoswitching characteristics, but their syntheses remain limited and inefficient. A new general method for the synthesis of tetra-ortho-chloro azobenzenes has been developed, which relies on direct palladium(II)-catalyzed C-H activation of pre existing standard azobenzenes. This late-stage functionalization has a broad substrate scope and can be used to create a variety of useful building blocks for the construction of more elaborate redshifted photopharmaceuticals. This method is used to prepare red-AzCA-4, a photoswitchable vanilloid that enables optical control of the cation channel TRPV1 with visible light. PMID- 26889886 TI - The mechanism of controllable dehydrogenation: CPMD study of M(BH4)x(NH3)y (M = Li, Mg) decomposition. AB - Amine metallic borohydrides were synthesized as a new series of hydrogen-storage materials. Their dehydrogenation can be controlled if appropriate metal centres are chosen. A typical example is LiBH4NH3 (ALB) and Mg(BH4)2(NH3)2 (AMgB) adopt the same symmetries but show totally different appearances when decomposed. Both ALB and AMgB are relatively new compounds designed as candidates for solid-state hydrogen storage. In this study, we have applied a Car-Parrinello molecular dynamic (CPMD) method to simulate the overall processes of their decomposition to figure out the mechanisms behind the difference in post-decomposition appearances. The polarization of Mg(2+) is almost two times larger than that of Li(+), making the Mg(2+) bond with nitrogen and boron stronger compared to that of Li(+), which improves the appearance of dehydrogenation of AMgB over that of ALB. PMID- 26889885 TI - Gradual neofunctionalization in the convergent evolution of trichomonad lactate and malate dehydrogenases. AB - Lactate and malate dehydrogenases (LDH and MDH) are homologous, core metabolic enzymes common to nearly all living organisms. LDHs have evolved convergently from MDHs at least four times, achieving altered substrate specificity by a different mechanism each time. For instance, the LDH of anaerobic trichomonad parasites recently evolved independently from an ancestral trichomonad MDH by gene duplication. LDH plays a central role in trichomonad metabolism by catalyzing the reduction of pyruvate to lactate, thereby regenerating the NAD+ required for glycolysis. Using ancestral reconstruction methods, we identified the biochemical and evolutionary mechanisms responsible for this convergent event. The last common ancestor of these enzymes was a highly specific MDH, similar to modern trichomonad MDHs. In contrast, the LDH lineage evolved promiscuous activity by relaxing specificity in a gradual process of neofunctionalization involving one highly detrimental substitution at the "specificity residue" (R91L) and many additional mutations of small effect. L91 has different functional consequences in LDHs and in MDHs, indicating a prominent role for epistasis. Crystal structures of modern-day and ancestral enzymes show that the evolution of substrate specificity paralleled structural changes in dimerization and alpha-helix orientation. The relatively small "specificity residue" of the trichomonad LDHs can accommodate a range of substrate sizes and may permit solvent to access the active site, both of which promote substrate promiscuity. The trichomonad LDHs present a multi-faceted counterpoint to the independent evolution of LDHs in other organisms and illustrate the diverse mechanisms by which protein function, structure, and stability coevolve. PMID- 26889887 TI - Development and validation of an algorithm for identifying urinary retention in a cohort of patients with epilepsy in a large US administrative claims database. AB - PURPOSE: The aim of this study was to develop and validate an insurance claims based algorithm for identifying urinary retention (UR) in epilepsy patients receiving antiepileptic drugs to facilitate safety monitoring. METHODS: Data from the HealthCore Integrated Research Database(SM) in 2008-2011 (retrospective) and 2012-2013 (prospective) were used to identify epilepsy patients with UR. During the retrospective phase, three algorithms identified potential UR: (i) UR diagnosis code with a catheterization procedure code; (ii) UR diagnosis code alone; or (iii) diagnosis with UR-related symptoms. Medical records for 50 randomly selected patients satisfying >=1 algorithm were reviewed by urologists to ascertain UR status. Positive predictive value (PPV) and 95% confidence intervals (CI) were calculated for the three component algorithms and the overall algorithm (defined as satisfying >=1 component algorithms). Algorithms were refined using urologist review notes. In the prospective phase, the UR algorithm was refined using medical records for an additional 150 cases. RESULTS: In the retrospective phase, the PPV of the overall algorithm was 72.0% (95%CI: 57.5 83.8%). Algorithm 3 performed poorly and was dropped. Algorithm 1 was unchanged; urinary incontinence and cystitis were added as exclusionary diagnoses to Algorithm 2. The PPV for the modified overall algorithm was 89.2% (74.6-97.0%). In the prospective phase, the PPV for the modified overall algorithm was 76.0% (68.4-82.6%). Upon adding overactive bladder, nocturia and urinary frequency as exclusionary diagnoses, the PPV for the final overall algorithm was 81.9% (73.7 88.4%). CONCLUSIONS: The current UR algorithm yielded a PPV > 80% and could be used for more accurate identification of UR among epilepsy patients in a large claims database. PMID- 26889888 TI - The effect of helmets on motorcycle outcomes in a level I trauma center in Connecticut. AB - OBJECTIVE: The State of Connecticut has a partial motorcycle helmet law, which has been linked to one of the lowest helmet compliance rates in the Northeast. We examine the clinical and financial impact of low motorcycle helmet use in the State of Connecticut. METHODS: A retrospective cohort study comparing the outcomes between helmeted and nonhelmeted motorcycle crash victims over a 12.5 year period, from July 2, 2002, to December 31, 2013. All patients who were admitted to the hospital after a motorcycle crash were included in the study. Patients were stratified into helmeted and nonhelmeted cohorts. Group differences were compared using t-test or Wilcoxon rank test for continuous variables and chi square test for dichotomous outcomes. Regression models were created to evaluate predictors of helmet use, alcohol and drugs as confounding variables, and factors that influenced hospital costs. RESULTS: The registry included 986 eligible patients. Of this group, 335 (34%) were helmeted and 651 (66%) were nonhelmeted. Overall, nonhelmeted patients had a worse clinical presentation, with lower Glasgow Coma Scale (GCS; P <.01), higher Injury Severity Score (ISS; P <.01), higher incidence of loss of consciousness (LOC; P <.01), longer intensive care unit (ICU; P <.01) admissions, and higher incidence of head (P <.01) or face injuries (P <.01). Nonhelmeted patients were also twice as more likely to die from their injuries (P =.04, odds ratio [OR] = 1.89, 95% confidence interval [CI], 1.02-3.45). Financially, nonhelmeted patients incurred mean hospital costs of $18,458, whereas helmeted patients incurred $14,970 (P =.18). ISS, GCS, and ICU length of stay were significantly correlated with increased hospital costs (P <.01). Not using a helmet was a significant predictor of mortality (P =.04) after adjusting for alcohol/drug use and age. CONCLUSIONS: Helmet use is associated with lower injury severity and increased survival after a motorcycle crash. These outcomes remained consistent even after controlling for age and alcohol and drug use. The medical and financial impact of Connecticut's partial helmet law should be carefully evaluated to petition for increased education and enforcement of helmet use. PMID- 26889889 TI - Maternity Outcomes in Manitoba Women: A Comparison between Midwifery-led Care and Physician-led Care at Birth. AB - BACKGROUND: Registered midwives, obstetricians/gynecologists, and general or family practice physicians (GPs) provide maternity care across Canada. Few North American studies have assessed whether maternity outcomes differ across these three groups. This study compared maternal and neonatal outcomes of low-risk pregnant women whose birth was attended by registered midwives, obstetricians/gynecologists, and family practice physicians in Winnipeg, Manitoba from 2001/02 to 2012/13. METHODS: Descriptive statistics and logistic regression were used to examine differences in types of intervention, mode of delivery, and outcomes by provider type among low-risk women. Logistic regression models controlled for socio-demographic and birth-related covariates. RESULTS: Low-risk births comprised 83,774 (48.7%) of total births (n = 171,910). The adjusted odds ratio (aOR), (95% confidence interval) for midwife vs OB/GYN showed women who had a midwife attend the birth had reduced odds of having an episiotomy 0.47 (0.40 0.54), epidural 0.25 (0.23-0.27), and cesarean delivery 0.13 (0.10-0.16) and their infants had less Neonatal Intensive Care Unit admissions 0.28 (0.18-0.43). The aOR for GP versus OB/GYN showed women who had a GP had reduced odds of having an epidural/spinal 0.83 (0.79-0.88) and cesarean delivery 0.44 (0.40-0.48). CONCLUSIONS: The effectiveness of Manitoba maternity services can be improved with increased use of integrated midwifery services. Future research should examine how midwifery and physician-led models of care differ, and the influence of these differences on birth outcomes and cost-effectiveness to the health care system. Improvement of data tracking systems is also needed. PMID- 26889890 TI - Editorial: Looking beyond the horizon--innovation in child psychology and psychiatry. AB - As readers will no doubt be well aware, the Journal of Child Psychology and Psychiatry dedicates an entire issue, once a year, to state-of-the-art authoritative reviews of research on some of the central issues in our field.(1) I like to think that in doing so we have been quietly undertaking a giant Pavlovian conditioning experiment: every year, as the spring flowers start to blossom (in the northern hemisphere at least), the nucleus accumbens of child psychologists and psychiatrists around the world begin to glow in anticipation of intellectual reward. PMID- 26889891 TI - Commentary: Finding out the best way to tailor psychological interventions for children and families--a commentary on Ng and Weisz (2016). AB - The article by Ng and Weisz () on how to build a science of personalized intervention for youth mental health is ambitious and wide-ranging, being packed with penetrating analyses and imaginative proposals that set the agenda for psychotherapeutic research for years to come. It is driven by the desire to make therapy more effective, and underpinned by the notion that if therapy can be fitted more closely to individual characteristics, results will be better. PMID- 26889892 TI - Commentary: The devastating effects of ignoring child maltreatment in psychiatry- a commentary on Teicher and Samson 2016. AB - Despite the numerous studies over the past 30 years that have clarified the devastating effects of child maltreatment on mental and physical health, the role of trauma within the caregiving system remains unrecognized both in our diagnostic systems and in our dominant treatment paradigms. Research of people with histories of caregiver abuse and neglect consistently demonstrates problems with concentration, anger, panic, depression, food intake, drugs, and sleep, as well as decreased Heart RateVariability, higher levels of stress hormones, and reduced or impaired immune response. Their relationship between documented brain changes and psychopathology is complex. Traumatic life experiences during childhood and adolescence are far more common than expected. The Centers for Disease Control and Prevention estimates that child maltreatment may be the most costly public health issue in the United States, Eradicating child abuse in America would reduce the overall rate of depression by more than half, alcoholism by two-thirds, and suicide, serious drug abuse, and domestic violence by three quarters. It would also have a significantly positive effect on workplace performance, and vastly decrease the need for incarceration. The current practice of applying multiple distinct comorbid diagnoses to traumatized children prevents a comprehensive treatment approach. Approaching their problems from a framework of memories of discreet traumatic ignores the fact that the damage affects the brain's neural circuitry and goes well beyond dealing with discrete painful events. Our great challenge is to learn to utilize the brain's neuroplasticity to reorganize defective brain circuits. PMID- 26889893 TI - Commentary: Not just genes--reclaiming a role for environmental influences on aetiology and outcome in autism. A commentary on Mandy and Lai (2016). AB - Mandy and Lai (2015) do the field a service in 'reclaiming' the role of pre- and postnatal environmental influences on the aetiology and course of autism spectrum conditions (ASC). This follows several decades where now discredited theories about putative psychogenic and biological disease models held sway, not least in the public mind. We discuss issues that arise from their review; including the need to identify how large the environmental influences on ASC are likely to be; the specificity of these environmental influences to ASC as opposed to a broader range of neurodevelopmental conditions and outcomes; how best to study complex interactions between genetic and environmental influences; and the promise of novel insights into their mechanisms of action. The review highlights current research that aims to better our understanding of the role of environmental factors in the aetiology and course of ASC and, in the near future, may offer the potential for personalised medicine approaches to intervention based on these discoveries. PMID- 26889894 TI - Commentary: Thinking outside the box about children's sleep--a commentary on Gregory and Sadeh (2016). AB - This commentary is intended to supplement the accompanying review of sleep problems in childhood psychiatric disorders by Gregory and Sadeh. A number of considerations are outlined because of their relevance to both clinical practice and research concerning assessment and treatment of sleep disturbance in children in general and especially those with psychiatric and/or neurological conditions. These considerations (which illustrate the importance of combined medical and psychological involvement) are as follows: the importance of screening for sleep disturbance which otherwise may well be overlooked; the need to specify sleep disorders rather than simply nonspecific sleep problems as this will guide choice of appropriate advice and treatment; the risk of sleep disorders being misdiagnosed because of clinicians' unfamiliarity with the sleep disorders field; the possibility that a child's sleep disturbance is of multiple aetiology; a wide range of treatments for disturbed sleep is now described from which a choice is possible given an accurate diagnosis; sleep problems may be intensified if a child's condition is complicated by intellectual disability but the same principles of assessment and management apply as in other children in the expectation that treatment can be effective. PMID- 26889895 TI - Commentary: Transdiagnostic neuroscience of child and adolescent mental disorders -differentiating decision-making in attention-deficit/hyperactivity disorder, conduct disorder, depression and anxiety. A commentary on Sonuga-Barke et al. (2016). AB - Sonuga-Barke, Cortese, Fairchild, and Stringaris offer us new insights not only on the neuropsychological processes and neurobiological mechanisms involved in the decision-making process but also how some of the most relevant child mental disorders might impact this process through a very comprehensive review of the pertinent literature. Although it is difficult to select specific points for discussing in a so dense review, I would like to highlight some aspects for 'whetting readers appetite' and seduce them to be in contact with the fascinating neurobiology behind an essential aspect of our lives. PMID- 26889896 TI - Annual Research Review: Neural contributions to risk-taking in adolescence- developmental changes and individual differences. AB - BACKGROUND: Risk-taking, which involves voluntary choices for behaviors where outcomes remain uncertain, undergoes considerable developmental changes during childhood, adolescence, and early adulthood. In addition, risk-taking is thought to be a key element of many externalizing disorders, such as ADHD, delinquency, conduct disorder, and substance abuse. In this review, we will discuss the potential adaptive and nonadaptive properties of risk-taking in childhood and adolescence. FINDINGS: We propose that the changes in brain architecture and function are a crucial element underlying these developmental trajectories. We first identify how subcortical and cortical interactions are important for understanding risk-taking behavior in adults. Next, we show how developmental changes in this network underlie changes in risk-taking behavior. Finally, we explore how these differences can be important for understanding externalizing behavioral disorders in childhood and adolescence. CONCLUSIONS: We conclude that longitudinal studies are of crucial importance for understanding these developmental trajectories, and many of these studies are currently underway. PMID- 26889897 TI - Commentary: Risk taking, impulsivity, and externalizing problems in adolescent development--commentary on Crone et al. 2016. AB - This commentary supports several important themes. These include the value in seeing risk taking as multicomponential (affective vs. deliberative risk taking), the importance of evaluating risk taking in relation to outcome, the necessity of expanding the brain networks studied in relation to risk taking, and the crucial interactions of risk taking with psychosocial context. We argue that more careful distinctions are needed between risk taking and different forms of impulsivity. Clearer differentiation of these constructs and their study together in brain imaging studies will clarify components of adolescent development and risk for externalizing behavior problems. PMID- 26889898 TI - Annual Research Review: On the developmental neuropsychology of substance use disorders. AB - BACKGROUND: Adolescence represents a period of development during which critical biological, as well as social and cognitive, changes occur that are necessary for the transition into adulthood. A number of researchers have suggested that the pattern of normative brain changes that occurs during this period not only predisposes adolescents to engage in risk behaviours, such as experimentation with drugs, but that they additionally make the adolescent brain more vulnerable to the direct pharmacological impact of substances of abuse. The neural circuits that we examine in this review involve cortico-basal-ganglia/limbic networks implicated in the processing of rewards, emotion regulation, and the control of behaviour, emotion and cognition. FINDINGS AND CONCLUSIONS: We identify certain neurocognitive and personality/comorbidity-based risk factors for the onset of substance misuse during adolescence, and summarise the evidence suggesting that these risk factors may be further impacted by the direct effect of drugs on the underlying neural circuits implicated in substance misuse vulnerability. PMID- 26889900 TI - Commentary: Surveying normal science for children's mental health--expanding reconnaissance to strong inference, trans-syndromal risk and social transactions. A response to Rutter & Pickles (2016). PMID- 26889899 TI - Commentary: Making the brain matter in assessing and treating adolescent substance use--a commentary on Conrod and Nikolaou (2016). AB - Adolescence represents a period of vulnerability to psychiatric problems due to a range of factors, including advances in social and cognitive abilities, increased levels of autonomy in decision-making and behavioral governance, and greater exposure to opportunities for risk-taking behavior. Adding to these psychological and social challenges, adolescence also is marked by robust maturational changes affecting both the microcircuitry and connectivity between widely distributed brain systems. These changes alter the communication among parallel, distributed brain networks, have implications for one's vulnerability to engage in risk behavior and make the brain particularly susceptible to external perturbations, such as exposure to neurotoxic substances. PMID- 26889901 TI - Commentary: Leveraging discovery science to advance child and adolescent psychiatric research--a commentary on Zhao and Castellanos 2016. AB - 'Big Data' and 'Population Imaging' are becoming integral parts of inspiring research aimed at delineating the biological underpinnings of psychiatric disorders. The scientific strategies currently associated with big data and population imaging are typically embedded in so-called discovery science, thereby pointing to the hypothesis-generating rather than hypothesis-testing nature of discovery science. In this issue, Yihong Zhao and F. Xavier Castellanos provide a compelling overview of strategies for discovery science aimed at progressing our understanding of neuropsychiatric disorders. In particular, they focus on efforts in genetic and neuroimaging research, which, together with extended behavioural testing, form the main pillars of psychopathology research. PMID- 26889902 TI - Immunogenetics of prostate cancer and benign hyperplasia--the potential use of an HLA-G variant as a tag SNP for prostate cancer risk. AB - Human leukocyte antigen G (HLA-G) is an immunomodulatory molecule with important roles both physiologically as well as an escape mechanism of cancer cells. In this study, we evaluated the impact of eight polymorphisms at the 3' untranslated region (3'UTR) of the HLA-G gene in the development of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). A total of 468 DNA samples of Brazilian men predominantly Euro-descendant with PCa (N = 187), BPH (N = 152) and healthy control individuals (N = 129) were evaluated. The HLA-G 3'UTR region was amplified by polymerase chain reaction (PCR), sequenced and genotyped to identify the 14 bp insertion/deletion (rs371194629), +3003T/C (rs1707), +3010C/G (rs1710), +3027A/C (rs17179101), +3035C/T (rs17179108), +3142G/C (rs1063320), +3187A/G (rs9380142) and +3196C/G (rs1610696) polymorphisms. Regression logistic and chi square tests were performed to verify the influence of single nucleotide polymorphisms (SNPs) in PCa and/or BPH susceptibility, as well as in PCa progression (clinicopathological status). Our data showed the UTR-4 haplotype as a risk factor to PCa in comparison with control [odds ratio (OR) 2.35, 95% confidence interval (CI) 1.39-3.96, P adjusted = 0.003) and BPH groups (OR 1.82, 95% CI 1.15-2.86, P adjusted = 0.030). Further, the 'non-14bp Ins_ + 3142G_+3187A' haplotype (OR 1.56, 95% CI 1.10-2.20, P adjusted = 0.036), the +3003CT genotype (OR 4.44, 95% CI 1.33-4.50, P adjusted = 0.032) and the +3003C allele (OR 2.33, 95% CI 1.38-3.92, P adjusted = 0.016) also conferred susceptibility to PCa. Our data suggest an important influence of HLA-G 3'UTR polymorphisms in PCa susceptibility and support the use of the +3003 variant as a tag SNP for PCa risk. PMID- 26889903 TI - Characterization of the novel HLA-A*02:431 allele identified in a Chinese Han individual. AB - HLA-A*02:431 differs from the closest allele HLA-A*02:03:01 by a nonsynonymous mutation at nucleotide 317 in exon 2. PMID- 26889904 TI - Identification of a new HLA-A*24 allele, A*24:309, in an Italian bone marrow donor. AB - A novel class I human leukocyte antigen allele HLA-A*24:309 is described. PMID- 26889905 TI - A novel null HLA-B allele, B*15:375N, due to a seven base pair deletion within exon 3. AB - Characterization of a novel HLA-B null allele, B*15:375N, with a seven base pair deletion in exon 3. PMID- 26889906 TI - Identification of a novel HLA-B*40 allele, HLA-B*40:324, by sequence-based typing, in a Chinese individual. AB - The new allele, HLA-B*40:324 differs from B*40:63 by two nucleotide changes in exon 3. PMID- 26889907 TI - Genomic sequence of HLA-B*41:43, a new HLA-B allele generated by an intralocus recombination mechanism. AB - HLA-B*41:43 has been generated by an intralocus recombination comprising B*41:02:01 and a B*14, 38, or 67 allele. PMID- 26889908 TI - Nomenclature for factors of the HLA system, update October 2015. PMID- 26889909 TI - Nomenclature for factors of the HLA system, update November 2015. PMID- 26889910 TI - Nomenclature for factors of the HLA system, update December 2015. PMID- 26889911 TI - Switching from sulphonylurea to a sodium-glucose cotransporter2 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia. AB - The aim of the present study was to assess the hypoglycaemia risk and safety of dapagliflozin compared with sulphonylurea during the fasting month of Ramadan. In this 12-week, randomized, open-label, two-arm parallel group study, 110 patients with type 2 diabetes who were receiving sulphonylurea and metformin were randomized either to receive 10 mg (n = 58) of dapagliflozin daily or to continue receiving sulphonylurea (n = 52). The primary outcome was to compare the effects of dapagliflozin and sulphonylurea on the proportions of patients with at least one episode of hypoglycaemia during Ramadan, as well as to assess the safety of dapagliflozin when used to treat patients observing Ramadan. A lower proportion of patients had reported or documented hypoglycaemia in the dapagliflozin group than in the sulphonylurea group: 4 (6.9%) versus 15 (28.8%); p = 0.002. The relative risk of any reported or documented hypoglycaemia in the 4th week of Ramadan was significantly lower in the dapagliflozin group: RR=0.24, 95%CI: 0.09, 0.68; p=0.002. No significance differences were observed between the two groups regarding postural hypotension (13.8 vs 3.8%; p = 0.210) or urinary tract infections (10.3 vs 3.8%; p = 0.277). In conclusion, fewer patients exhibited hypoglycaemia in the dapagliflozin group than in the sulphonylurea group. PMID- 26889912 TI - Mitochondrial gamma carbonic anhydrases are required for complex I assembly and plant reproductive development. AB - Complex I of the mitochondrial electron transport chain (mETC) in plants contains an extra domain that is made up from proteins homologous to prokaryotic gamma carbonic anhydrases (gammaCA). This domain has been suggested to participate in complex I assembly or to support transport of mitochondrial CO2 to the chloroplast. Here, we generated mutants lacking CA1 and CA2 - two out of three CA proteins in Arabidopsis thaliana. Double mutants were characterized at the developmental and physiological levels. Furthermore, the composition and activity of the mETC were determined, and mutated CA versions were used for complementation assays. Embryo development of double mutants was strongly delayed and seed development stopped before maturation. Mutant plants could only be rescued on sucrose media, showed severe stress symptoms and never produced viable seeds. By contrast, callus cultures were only slightly affected in growth. Complex I was undetectable in the double mutants, but complex II and complex IV were upregulated concomitant with increased oxygen consumption in mitochondrial respiration. Ectopic expression of inactive CA variants was sufficient to complement the mutant phenotype. Data indicate that CA proteins are structurally required for complex I assembly and that reproductive development is dependent on the presence of complex I. PMID- 26889913 TI - Homogeneous and Heterogeneous Photocatalytic Water Oxidation by Persulfate. AB - Photocatalytic water oxidation by persulfate (Na2 S2 O8 ) with [Ru(bpy)3 ](2+) (bpy=2,2'-bipyridine) as a photocatalyst provides a standard protocol to study the catalytic reactivity of water oxidation catalysts. The yield of evolved oxygen per persulfate is regarded as a good index for the catalytic reactivity because the oxidation of bpy of [Ru(bpy)3 ](2+) and organic ligands of catalysts competes with the catalytic water oxidation. A variety of metal complexes act as catalysts in the photocatalytic water oxidation by persulfate with [Ru(bpy)3 ](2+) as a photocatalyst. Herein, the catalytic mechanisms are discussed for homogeneous water oxidation catalysis. Some metal complexes are converted to metal oxide or hydroxide nanoparticles during the photocatalytic water oxidation by persulfate, acting as precursors for the actual catalysts. The catalytic reactivity of various metal oxides is compared based on the yield of evolved oxygen and turnover frequency. A heteropolynuclear cyanide complex is the best catalyst reported so far for the photocatalytic water oxidation by persulfate and [Ru(bpy)3 ](2+) , affording 100 % yield of O2 per persulfate. PMID- 26889914 TI - 3D Nanoporous Metal Phosphides toward High-Efficiency Electrochemical Hydrogen Production. AB - Free-standing nanoporous metal phosphides are fabricated by a novel top-down method, by selectively leaching less-stable metal phases from rapidly solidified two-phase metal-phosphorus alloys. The phosphide phases with relatively high electrochemical stability are left as the skeletons of nanoporous structures. The resultant nanoporous phosphides with tunable pore size and porosity show superior catalytic activities toward electrochemical hydrogen production. PMID- 26889915 TI - The air quality forecast rote: Recent changes and future challenges. AB - Air quality forecasting is a recent development, with most programs initiated only in the last 20 years. During the last decade, forecast preparation procedure the forecast rote-has changed dramatically. This paper summarizes the unique challenges posed by air quality forecasting, details the current forecast rote, and analyzes prospects for future improvements. Because air quality forecasts must diagnose and predict several pollutants and their precursors in addition to standard meteorological variables, it is, compared with weather forecasts, a higher-uncertainty forecast. Forecasters seek to contain the uncertainty by "anchoring" the forecast, using an a priori field, and then "adjusting" the forecast using additional information. The air quality a priori, or first guess, field is a blend of past, current, and near-term future observations of the pollutants of interest, on both local and regional scales, and is typically coupled with predicted air parcel trajectories. Until recently, statistical methods, based on long-term training data sets, were used to adjust the first guess. However, reductions in precursor emissions in the United States, beginning in the late 1990s and continuing to the present, eroded the stationarity assumption for the training data sets and degraded forecast skill. Beginning in the mid-2000s, output from modified numerical air quality prediction (NAQP) models, originally developed to test pollution control strategies, became available in near real time for forecast support. The current adjustment process begins with the analyses and postprocessing of individual NAQP models and their ad hoc ensembles, often in concert with new statistical techniques. The final adjustment step uses forecaster expertise to assess the impact of mesoscale features not resolved by the NAQP models. It is expected that advances in model resolution, chemical data assimilation, and the formulation of emissions fields will improve mesoscale predictions by NAQP models and drive future changes in the forecast rote. IMPLICATIONS: Routine air quality forecasts are now issued for nearly all the major U.S. metropolitan areas. Methods of forecast preparation-the forecast rote-have changed significantly in the last decade. Numerical air quality models have matured and are now an indispensable part of the forecasting process. All forecasting methods, particularly statistically based models, must be continually calibrated to account for ongoing local- and regional-scale emission reductions. PMID- 26889916 TI - Cardiac troponin in patients hospitalized with acute decompensated heart failure: A systematic review and meta-analysis. AB - BACKGROUND: Elevated cardiac troponin (cTn) is often observed in patients with acute decompensated heart failure (ADHF). We assessed the magnitude of association and quality of supporting evidence between cTn and clinically important outcomes in persons hospitalized for ADHF. METHODS: We searched MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through February 28, 2015. The outcomes analyzed included hospital length of stay (LOS), readmissions, and mortality. Random effects meta analysis was used to combine outcomes across studies. RESULTS: We included 26 clinical studies. A detectable or elevated cTn was associated with increased LOS (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01-1.10), increased in hospital mortality (OR: 2.57; 95% CI: 2.27-2.91), and a composite of mortality and major adverse events (OR: 1.33; 95% CI: 1.03-1.71) during hospitalization. ADHF patients with a detectable or elevated cTn were at increased risk for mortality and composite of mortality and readmission over the short term (mortality OR: 2.11; 95% CI: 1.43-3.12; composite OR: 2.81; 95% CI: 1.60-4.92), intermediate term (mortality OR: 2.21; 95% CI: 1.46-3.35; composite OR: 2.30; 95% CI: 1.78-2.99), and long term (mortality OR: 3.69; 95% CI: 2.64-5.18; composite OR: 3.49; 95% CI: 2.08-5.84). The overall confidence in estimates was moderate. CONCLUSIONS: Among ADHF patients, a detectable or elevated cTn identifies subjects at increased risk for adverse clinical outcomes during acute hospitalization and those at higher risk for postdischarge mortality and composite of readmission and mortality. Journal of Hospital Medicine 2016;11:446 454. 2016 Society of Hospital Medicine. PMID- 26889917 TI - Synthesis of Keratin-based Nanofiber for Biomedical Engineering. AB - Electrospinning, due to its versatility and potential for applications in various fields, is being frequently used to fabricate nanofibers. Production of these porous nanofibers is of great interest due to their unique physiochemical properties. Here we elaborate on the fabrication of keratin containing poly (epsilon-caprolactone) (PCL) nanofibers (i.e., PCL/keratin composite fiber). Water soluble keratin was first extracted from human hair and mixed with PCL in different ratios. The blended solution of PCL/keratin was transformed into nanofibrous membranes using a laboratory designed electrospinning set up. Fiber morphology and mechanical properties of the obtained nanofiber were observed and measured using scanning electron microscopy and tensile tester. Furthermore, degradability and chemical properties of the nanofiber were studied by FTIR. SEM images showed uniform surface morphology for PCL/keratin fibers of different compositions. These PCL/keratin fibers also showed excellent mechanical properties such as Young's modulus and failure point. Fibroblast cells were able to attach and proliferate thus proving good cell viability. Based on the characteristics discussed above, we can strongly argue that the blended nanofibers of natural and synthetic polymers can represent an excellent development of composite materials that can be used for different biomedical applications. PMID- 26889918 TI - The trials and tribulations of repurposing metformin and other generic drugs for tuberculosis. AB - There are a number of generic drugs that might be useful in treating tuberculosis, but will they ever get to the patients who need them? They might, but not without a lot of help. There are intellectual property issues, endpoint issues, cost of research issues, economic incentive issues, preclinical validation issues, "who is in charge" issues and many more. It is clear that repurposed generic drugs have the potential to make a safe, effective, quick and affordable impact on a global disease of poverty such as tuberculosis. But without the economic incentives that are usually in place for drug development, can we muster the scientific, economic and governmental support to bring them to the patients? PMID- 26889919 TI - Formation of Hybrid Perovskite Tin Iodide Single Crystals by Top-Seeded Solution Growth. AB - Hybrid perovskites have generated a great deal of interest because of their potential in photovoltaic applications. However, the toxicity of lead means that there is interest in finding a nontoxic substitute. Bulk single crystals of both cubic CH3NH3 SnI3 and CH(NH2)2 SnI3 were obtained by using the top-seeded solution growth method under an ambient atmosphere. Structural refinement, band gap, thermal properties, and XPS measurements of CH3NH3 SnI3 and CH(NH2)2 SnI3 single crystals are also reported in detail. These results should pave the way for further applications of CH3NH3 SnI3 and CH(NH2)2 SnI3. PMID- 26889920 TI - Visual demands in modern Australian primary school classrooms. AB - BACKGROUND: The visual demands of modern classrooms are poorly understood yet are relevant in determining the levels of visual function required to perform optimally within this environment. METHODS: Thirty-three Year 5 and 6 classrooms from eight south-east Queensland schools were included. Classroom activities undertaken during a full school day (9 am to 3 pm) were observed and a range of measurements recorded, including classroom environment (physical dimensions, illumination levels), text size and contrast of learning materials, habitual working distances (distance and estimated for near) and time spent performing various classroom tasks. These measures were used to calculate demand-related minimum criteria for distance and near visual acuity, contrast and sustained use of accommodation and vergence. RESULTS: The visual acuity demands for distance and near were 0.33 +/- 0.13 and 0.72 +/- 0.09 logMAR, respectively (using habitual viewing distances and smallest target sizes) or 0.33 +/- 0.09 logMAR assuming a 2.5 times acuity reserve for sustained near tasks. The mean contrast levels of learning materials at distance and near were greater than 70 per cent. Near tasks (47 per cent) dominated the academic tasks performed in the classroom followed by distance (29 per cent), distance to near (15 per cent) and computer based (nine per cent). On average, children engaged in continuous near fixation for 23 +/- 5 minutes at a time and during distance-near tasks performed fixation changes 10 +/- 1 times per minute. The mean estimated habitual near working distance was 23 +/- 1 cm (4.38 +/- 0.24 D accommodative demand) and the vergence demand was 0.86 +/- 0.07(Delta) at distance and 21.94 +/- 1.09(Delta) at near assuming an average pupillary distance of 56 mm. CONCLUSIONS: Relatively high levels of visual acuity, contrast demand and sustained accommodative-convergence responses are required to meet the requirements of modern classroom environments. These findings provide an evidence base to inform prescribing guidelines and develop paediatric vision screening protocols and referral criteria. PMID- 26889923 TI - Cationic Cobalt(III) Catalyzed Indole Synthesis: The Regioselective Intermolecular Cyclization of N-Nitrosoanilines and Alkynes. AB - The unique regioselectivity and reactivity of cobalt(III) in the direct cyclization of N-nitrosoanilines with alkynes for the expedient synthesis of N substituted indoles is demonstrated. In the presence of a cobalt(III) catalyst, high regioselectivity was observed when using unsymmetrical meta-substituted N nitrosoanilines. Moreover, internal alkynes bearing electron-deficient groups, which are almost unreactive in the [Cp*Rh(III)]-catalyzed system, display good reactivity in this transformation. PMID- 26889924 TI - Gender Disparities in Lipid-Lowering Therapy in Cardiovascular Disease: Insights from a Managed Care Population. AB - BACKGROUND: Numerous studies have documented the strong inverse relationship between low-density lipoprotein cholesterol (LDL-C) levels and atherosclerotic cardiovascular disease (ASCVD). However, women are less likely to be screened for hypercholesterolemia, receive lipid-lowering therapy (LLT), and achieve optimal LDL-C levels. MATERIALS AND METHODS: Data were extracted from a U.S. administrative claims database between January 2008 and December 2012 for patients with established ASCVD. The earliest date of valid LDL-C value was defined as the index date. Patients were followed for +/-12 months from the index date and were stratified by gender, by baseline LDL-C level, and whether they were initially treated with a LLT then propensity score matched by gender using demographic and clinical characteristics. Both descriptive statistics and logistic regression models were used to explore the association of gender with the frequency of LDL-C monitoring, LLT treatment initiation in initially untreated patients, and prescribing patterns in initially treated patients. RESULTS: A total of 76,414 subjects with established ASCVD were identified; 42% of the sample was women. In the unmatched cohort, 50.3% of men and 32.0% of women were prescribed a preindex statin (p < 0.0001). Among matched patients (n = 51,764), women initially treated with LLT were significantly less likely to receive a prescription for a higher potency LLT. Even among those with LDL-C levels above 160 mg/dL, women were more likely to discontinue LLT, odds ratio (95% confidence interval) 1.8 (1.2-2.3). Female gender and older age were significant predictors of discontinuation, and the potency of the index medication was the strongest predictor of dose titration. Initially untreated women were less likely to initiate LLT treatment than men, irrespective of index LDL-C levels (p < 0.0001). CONCLUSIONS: The observed disparities further reinforce the need for targeted efforts to reduce the gender gap for secondary prevention in women at high risk of cardiovascular disease. PMID- 26889922 TI - The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies. AB - Particular concerns have been raised regarding the association between non vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a systematic review with a meta-analysis to examine the association between NOACs and GIB in real-life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random-effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta-analysis, enrolling 1442 GIB cases among 106 626 dabigatran users (49 486 patient-years), and 184 GIB cases among 10 713 rivaroxaban users (4046 patient-years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient-years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose-related effect of dabigatran, with a significantly higher risk of GIB for 150 mg b.i.d. (RR = 1.51, 95% CI 1.34, 1.70) but not for 75 mg b.i.d. or 110 mg b.i.d.. In addition, the use of proton pump inhibitors (PPIs)/histamine H2-receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta-analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk. PMID- 26889925 TI - Rapid identification of pesticides in human oral fluid for emergency management by thermal desorption electrospray ionization/mass spectrometry. AB - Self-poisoning with pesticides accounts for approximately one-third of all suicides worldwide. To expedite rescue in the emergency department, it is essential to develop a point-of-care analytical method for rapid identification of ingested pesticides. In this study, five of the most common pesticides ingested by self-poisoning patients in Taiwan were analyzed from oral fluid samples. Pesticide-oral fluid mixtures were applied on a cotton swab and then transferred into methanol. A metallic probe was used to sample the methanol solution for subsequent thermal desorption-electrospray ionization mass spectrometry analysis. Altogether, pesticide sampling, transfer, desorption, ionization, and detection took less than 1 min. The reproducibility of this method (n = 6) was shown in the observed low-relative standard deviation (<7%) in the detection of pesticide in oral fluid. The detection limits of the pesticides in oral fluid obtained from four human subjects by thermal desorption electrospray ionization mass spectrometry were between 1-10 ppb with relative standard deviation 10.7%. Moreover, in this study, linear responses of five pesticides in oral fluid with concentrations between 1 ppb-1 ppm (R2 between 0.9938 and 0.9988) were observed. As the whole analytical process is extremely short, this technique allows for early non-invasive point-of-care identification of pesticides in the oral fluid of self-poisoning patients in the emergency room, providing important toxicological information for decision-making during critical resuscitation. PMID- 26889926 TI - Effects of peptide acetylation and dimethylation on electrospray ionization efficiency. AB - Peptide acetylation and dimethylation have been widely used to derivatize primary amino groups (peptide N-termini and the epsilon-amino group of lysines) for chemical isotope labeling of quantitative proteomics or for affinity tag labeling for selection and enrichment of labeled peptides. However, peptide acetylation results in signal suppression during electrospray ionization (ESI) due to charge neutralization. In contrast, dimethylated peptides show increased ionization efficiency after derivatization, since dimethylation increases hydrophobicity and maintains a positive charge on the peptide under common LC conditions. In this study, we quantitatively compared the ESI efficiencies of acetylated and dimethylated model peptides and tryptic peptides of BSA. Dimethylated peptides showed higher ionization efficiency than acetylated peptides for both model peptides and tryptic BSA peptides. At the proteome level, peptide dimethylation led to better protein identification than peptide acetylation when tryptic peptides of mouse brain lysate were analyzed with LC-ESI-MS/MS. These results demonstrate that dimethylation of tryptic peptides enhanced ESI efficiency and provided up to two-fold improved protein identification sensitivity in comparison with acetylation. PMID- 26889927 TI - Negative ion MALDI-TOF MS, ISD and PSD of neutral underivatized oligosaccharides without anionic dopant strategies, using 2,5-DHAP as a matrix. AB - Oligosaccharides represent complex class of analytes for mass spectrometric analysis due to the high variety of structural isomers concerning glycosidic linkages and possible branching. A systematic study of the negative ion mode matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of various neutral oligosaccharides under selection of an appropriate matrix, like 2,5 dihydroxyacetophenone (2,5-DHAP) is reported here, without commonly used anion dopant strategies. Nevertheless, we were able to generate relevant in-source decay (ISD) cross-ring fragment ions, typically obtained in the negative ion mode. Data observed indicate that the intrinsic property of the terminal non reduced aldose is crucial for this behavior. A systematic study of the post source decay (PSD) of molecular, pseudomolecular and ISD cross-ring cleavage precursor ions is reported here. A direct comparison of the positive and negative ion mode MALDI MS1 and PSD behavior of neutral oligosaccharides could also be performed under the use of the same matrix preparation, because 2,5-DHAP is fully compatible with positive ion mode acquisition. We found that PSD spectra of deprotonated neutral oligosaccharides obtained in the negative ion mode are richer, because they contained both glycosidic and cross-ring fragment ions. However, we also found that cross-ring fragment ions are readily produced in the positive ion mode when potassiated precursor ions were selected. In addition, we show evidence that non-anionic dopants and specific instrumental parameters can also significantly influence the ISD fragmentation. Taken together, our results should increase our understanding of oligosaccharide behavior in the negative ion mode as well as increase our knowledge regarding many aspects of in-source MALDI chemistry. PMID- 26889928 TI - A novel method for determination of inorganic oxyanions by electrospray ionization mass spectrometry using dehydration reactions. AB - Novel methods for the determination of inorganic oxyanions by electrospray (ES) ionization mass spectrometry have been developed using dehydration reactions between oxyanions and carboxylic acids at the ES interface. Twelve oxyanions (VO3 (-) , CrO4 (2-) , MoO4 (2-) , WO4 (2-) , BO3 (3-) , SiO3 (2-) , SiO4 (4-) , AsO4 (4-) , AsO2 (-) , SeO4 (2-) , SeO3 (2-) and NO2 (-) ), out of 16 tested, reacted with at least one of four aminopolycarboxylic acids, i.e. iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), trans-1,2-diaminocyclohexane-N,N,N',N' tetraacetic acid and triethylenetetramine-N,N,N',N",N'",N'"-hexaacetic acid, at the ES interface to produce the dehydration products that gave intense mass ion responses, sufficient for trace analysis. As examples, trace determinations of Cr(VI) and silica in water samples were achieved after online ion exchange chromatography, where the dehydration product of CrO4 (2-) and NTA (m/z 290) and that of SiO4 (4-) and IDA (m/z 192) were measured. The limits of detection of the respective methods were 17 nM (0.83 ng Cr/ml) for Cr(VI) and 0.17 MUM (4.8 ng Si/mL) for SiO4 (4-) . PMID- 26889929 TI - Low-pressure barrier discharge ion source using air as a carrier gas and its application to the analysis of drugs and explosives. AB - In this work, a low-pressure air dielectric-barrier discharge (DBD) ion source using a capillary with the inner diameter of 0.115 and 12 mm long applicable to miniaturized mass spectrometers was developed. The analytes, trinitrotoluene (TNT), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), 1,3,5,7-tetranitroperhydro 1,3,5,7-tetrazocine (HMX), pentaerythritol tetranitrate (PETN), nitroglycerine (NG), hexamethylene triperoxide diamine (HMTD), caffeine, cocaine and morphine, introduced through the capillary, were ionized by a low-pressure air DBD. The ion source pressures were changed by using various sizes of the ion sampling orifice. The signal intensities of those analytes showed marked pressure dependence. TNT was detected with higher sensitivity at lower pressure but vice versa for other analytes. For all analytes, a marked signal enhancement was observed when a grounded cylindrical mesh electrode was installed in the DBD ion source. Among nine analytes, RDX, HMX, NG and PETN could be detected as cluster ions [analyte + NO3 ](-) even at low pressure and high temperature up to 180 degrees C. The detection indicates that these cluster ions are stable enough to survive under present experimental conditions. The unexpectedly high stabilities of these cluster ions were verified by density functional theory calculation. PMID- 26889930 TI - Critical assessment of ionization patterns and applications of ambient desorption/ionization mass spectrometry using FAPA-MS. AB - Ambient desorption/ionization mass spectrometry (MS) has gained growing interest during the last decade due to its high analytical performance and yet simplicity. Here, one of the recently developed ambient desorption/ionization MS sources, the flowing atmospheric-pressure afterglow (FAPA) source, was investigated in detail regarding background ions and typical ionization patterns in the positive as well as the negative ion mode for a variety of compound classes, comprising alkanes, alcohols, aldehydes, ketones, carboxylic acids, organic peroxides and alkaloids. A broad range of signals for adducts and losses was found, besides the usually emphasized detection of quasimolecular ions, i.e. [M + H](+) and [M - H](-) in the positive and the negative mode, respectively. It was found that FAPA-MS is best suited for polar analytes containing nitrogen and/or oxygen functionalities, e.g. carboxylic acids, with low molecular weights and relatively high vapor pressures. In addition, the source was used in proof-of-principle studies, illustrating the capabilities and limitations of the technique: Firstly, traces of cocaine were detected and unambiguously identified on euro banknotes using FAPA ionization in combination with tandem MS, suggesting a correlation between cocaine abundance and age of the banknote. Secondly, FAPA-MS was used for the identification of acidic marker compounds in organic aerosol samples, indicating yet-undiscovered matrix and sample surface effects of ionization pathways in the afterglow region. PMID- 26889931 TI - Independent highly sensitive characterization of asparagine deamidation and aspartic acid isomerization by sheathless CZE-ESI-MS/MS. AB - Amino acids residues are commonly submitted to various physicochemical modifications occurring at physiological pH and temperature. Post-translational modifications (PTMs) require comprehensive characterization because of their major influence on protein structure and involvement in numerous in vivo process or signaling. Mass spectrometry (MS) has gradually become an analytical tool of choice to characterize PTMs; however, some modifications are still challenging because of sample faint modification levels or difficulty to separate an intact peptide from modified counterparts before their transfer to the ionization source. Here, we report the implementation of capillary zone electrophoresis coupled to electrospray ionization tandem mass spectrometry (CZE-ESI-MS/MS) by the intermediate of a sheathless interfacing for independent and highly sensitive characterization of asparagine deamidation (deaN) and aspartic acid isomerization (isoD). CZE selectivity regarding deaN and isoD was studied extensively using different sets of synthetic peptides based on actual tryptic peptides. Results demonstrated CZE ability to separate the unmodified peptide from modified homologous exhibiting deaN, isoD or both independently with a resolution systematically superior to 1.29. Developed CZE-ESI-MS/MS method was applied for the characterization of monoclonal antibodies and complex protein mixture. Conserved CZE selectivity could be demonstrated even for complex samples, and foremost results obtained showed that CZE selectivity is similar regardless of the composition of the peptide. Separation of modified peptides prior to the MS analysis allowed to characterize and estimate modification levels of the sample independently for deaN and isoD even for peptides affected by both modifications and, as a consequence, enables to distinguish the formation of l-aspartic acid or d-aspartic acid generated from deaN. Separation based on peptide modification allowed, as supported by the ESI efficiency provided by CZE-ESI-MS/MS properties, and enabled to characterize and estimate studied PTMs with an unprecedented sensitivity and proved the relevance of implementing an electrophoretic driven separation for MS-based peptide analysis. PMID- 26889932 TI - Detection of uranium in industrial and mines samples by microwave plasma torch mass spectrometry. AB - Microwave plasma torch (MPT), traditionally used as the light source for atomic emission spectrophotometry, has been employed as the ambient ionization source for sensitive detection of uranium in various ground water samples with widely available ion trap mass spectrometer. In the full-scan mass spectra obtained in the negative ion detection mode, uranium signal was featured by the uranyl nitrate complexes (e.g. [UO2 (NO3 )3 ](-) ), which yielded characteristic fragments in the tandem mass spectrometry experiments, allowing confident detection of trace uranium in water samples without sample pretreatment. Under the optimal experimental conditions, the calibration curves were linearly responded within the concentration levels ranged in 10-1000 ug.l(-1) , with the limit of detection (LOD) of 31.03 ng.l(-1) . The relative standard deviations (RSD) values were 2.1-5.8% for the given samples at 100 ug.l(-1) . The newly established method has been applied to direct detection of uranium in practical mine water samples, providing reasonable recoveries 90.94-112.36% for all the samples tested. The analysis of a single sample was completed within 30 s, showing a promising potential of the method for sensitive detection of trace uranium with improved throughput. PMID- 26889933 TI - Gas phase conversion of triphosphate to trimetaphosphate. PMID- 26889934 TI - Vacuum ultraviolet photoionization mass spectrometric study of cyclohexene. AB - In this work, photoionization and dissociation of cyclohexene have been studied by means of coupling a reflectron time-of-flight mass spectrometer with the tunable vacuum ultraviolet (VUV) synchrotron radiation. The adiabatic ionization energy of cyclohexene as well as the appearance energies of its fragment ions C6 H9 (+) , C6 H7 (+) , C5 H7 (+) , C5 H5 (+) , C4 H6 (+) , C4 H5 (+) , C3 H5 (+) and C3 H3 (+) were derived from the onset of the photoionization efficiency (PIE) curves. The optimized structures for the transition states and intermediates on the ground state potential energy surfaces related to photodissociation of cyclohexene were characterized at the omegaB97X-D/6-31+g(d,p) level. The coupled cluster method, CCSD(T)/cc-pVTZ, was employed to calculate the corresponding energies with the zero-point energy corrections by the omegaB97X-D/6-31+g(d,p) approach. Combining experimental and theoretical results, possible formation pathways of the fragment ions were proposed and discussed in detail. The retro Cope rearrangement was found to play a crucial role in the formation of C4 H6 (+) , C4 H5 (+) and C3 H5 (+) . Intramolecular hydrogen migrations were observed as dominant processes in most of the fragmentation pathways of cyclohexene. The present research provides a clear picture of the photoionization and dissociation processes of cyclohexene in the 8- to 15.5-eV photon energy region. PMID- 26889935 TI - Low C24-OH and C22-OH sulfatides in human renal cell carcinoma. PMID- 26889937 TI - Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures. AB - There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively. PMID- 26889938 TI - Photoluminescence and electron paramagnetic resonance properties of a potential phototherapic agent: MMgF4 :Gd3+ (M = Ba, Sr) sub-microphosphors. AB - Novel narrow band UVB-emitting phosphors, BaMgF4 :Gd3+ and SrMgF4 :Gd3+ phosphors, were synthesized using a co-precipitation synthesis method. X-Ray diffraction analysis was carried out to confirm compound formation, phase purity and crystallinity of the phosphor. At 274 nm excitation, phosphors show a sharp narrow band emission at 313 nm that can be assigned to 6 P7/2 -> 8 S7/2 transition of the Gd3+ ion. With increasing dopant concentration, intensity enhances and then decreases after a certain concentration, which is an indication of concentration quenching taking place in the phosphor. Scanning electron microscopy images of the phosphor show agglomerated particles in the sub-micron range. Particles range in size from 600 to 800 nm. Electron paramagnetic resonance studies of the phosphors were carried out to detect radicals present in the prepared phosphor. With narrow band UVB emission, phosphor seems to be a good candidate for UV phototherapy application. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889939 TI - Cytotoxicity of various chemicals and mycotoxins in fresh primary duck embryonic fibroblasts: a comparison to HepG2 cells. AB - To screen cost-effectively the overall toxicity of a sample, particularly in the case of food and feed ingredient quality control, a sensitive bioassay is necessary. With the wide variety of cytotoxicity assays, performance comparison between assays using different cells has become of interest. Fresh primary duck embryonic fibroblasts (DEF) were hypothesized to be a sensitive tool for in vitro cytotoxicity screening; cell viability of DEF in response to various cytotoxins was determined and compared with response of HepG2 cells. The IC50 values by the alamar blue assay in the DEF cells had a high correlation (R(2) = 0.96) with those obtained in HepG2 cells. Within the same toxin, primary DEF yielded significantly lower IC50 values than that obtained from HepG2 cells using the MTT and alamar blue assay. Additionally, primary DEF responded to all mycotoxins tested using the alamar blue assay, while HepG2 was less sensitive, particularly at short exposure times. The estimated IC50 for aflatoxin B1 , fumonisins B1 and deoxynivalenol in DEF after 72 h incubation were 3.69, 4.19 and 1.26 MUg ml(-1) , respectively. Results from the current study suggest that primary DEF are more sensitive to cytotoxins and mycotoxins compared to HepG2, and thus may have great potential as an effective tool for cytotoxicity assessment. The question remains whether in vitro IC50 values can accurately predict in vivo toxicity; however, the current study accentuates the need for further attention to identify sensitive cell models for in vitro cytotoxicity screening and subsequent exploration of species-specific prediction models for in vivo toxicity. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26889940 TI - AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet. AB - Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions. PMID- 26889941 TI - Effect of n-3 and n-6 Polyunsaturated Fatty Acids on Microsomal P450 Steroidogenic Enzyme Activities and In Vitro Cortisol Production in Adrenal Tissue From Yorkshire Boars. AB - Dysregulation of adrenal glucocorticoid production is increasingly recognized to play a supportive role in the metabolic syndrome although the mechanism is ill defined. The adrenal cytochrome P450 (CYP) enzymes, CYP17 and CYP21, are essential for glucocorticoid synthesis. The omega-3 and omega-6 polyunsaturated fatty acids (PUFA) may ameliorate metabolic syndrome, but it is unknown whether they have direct actions on adrenal CYP steroidogenic enzymes. The aim of this study was to determine whether PUFA modify adrenal glucocorticoid synthesis using isolated porcine microsomes. The enzyme activities of CYP17, CYP21, 11beta hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase (H6PDH), and CYP2E1 were measured in intact microsomes treated with fatty acids of disparate saturated bonds. Cortisol production was measured in a cell-free in vitro model. Microsomal lipid composition after arachidonic acid (AA) exposure was determined by sequential window acquisition of all theoretical spectra-mass spectrometry. Results showed that adrenal microsomal CYP21 activity was decreased by docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid, alpha-linolenic acid, AA, and linoleic acid, and CYP17 activity was inhibited by DPA, DHA, eicosapentaenoic acid, and AA. Inhibition was associated with the number of the PUFA double bonds. Similarly, cortisol production in vitro was decreased by DPA, DHA, and AA. Endoplasmic enzymes with intraluminal activity were unaffected by PUFA. In microsomes exposed to AA, the level of AA or oxidative metabolites of AA in the membrane was not altered. In conclusion, these observations suggest that omega-3 and omega-6 PUFA, especially those with 2 or more double bonds (DPA, DHA, and AA), impede adrenal glucocorticoid production. PMID- 26889943 TI - Correction to First Step into Space: Performance and Morphological Evolution of P3HT:PCBM Bulk Heterojunction Solar Cells under AM0 Illumination. PMID- 26889942 TI - Perfluoroalkyl Substances (PFASs) in Marine Mammals from the South China Sea and Their Temporal Changes 2002-2014: Concern for Alternatives of PFOS? AB - Perfluorinated sulfonic acids (PFSAs) and perfluorinated carboxylic acids (PFCAs), as well as the replacement for the phase-out C8 PFSAs were determined in the liver samples of Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) from the South China Sea between 2002 and 2014. Levels of total perfluoroalkyl substances (PFASs) in samples ranged from 136-15,300 and 30.5-2,720 ng/g dw for dolphin and porpoise, respectively. Significant increasing trends of several individual PFCAs and perfluorobutane sulfonate (PFBS) were found in cetacean samples from 2002 to 2014, whereas no significant temporal trends of ?PFASs appeared over the sampling period. This pattern may be attributed to the increasing usage of PFCAs and C4-based PFSAs following the restriction/voluntary withdrawal of the production and use of perfluorooctane sulfonate (PFOS) related products. In addition, significantly increasing temporal shifting trends of PFOS to PFBS were observed in the dolphin liver samples. This pattern may be attributed to the substitution of PFOS by its alternative, PFBS. The highest levels of PFOS were observed in the liver samples of dolphin as compared with other marine mammal studies published since 2006, indicating high contamination of PFAS in the South China region. An assessment of relatively high concentrations of C8-based PFASs in the liver samples of cetaceans predicted that concentrations of PFOS would be expected to affect some proportion of the cetacean populations studied, based on the toxicity thresholds derived. PMID- 26889945 TI - Using a real-life case scenario to integrate additional health professions students into an existing interprofessional team seminar. AB - The World Health Organization stated that the goal of interprofessional education (IPE) is to prepare students as collaboration-ready members of interprofessional care teams. Educators try to create meaningful and relevant learning experiences for multiple health professions students. A longitudinal Interprofessional Team Seminar (IPTS) course includes over 650 students from seven health professions at the professional training level. Recommendations from the National Athletic Trainers' Association (NATA) promote the inclusion of athletic training (AT) students in IPE initiatives. A new IPTS module included AT students focusing on the attributes of rapidly forming and different care teams as the patient transitions from an on-field injury, to acute care, inpatient care, and rehabilitative care, and back to activities of daily living. Qualitative review of reflections from the students assessed the impact of these IPTS modules. The intentional design of this course, focusing on behaviours of collaborative practice and supporting students to be collaboration ready, effectively introduced and highlighted profession-specific strengths and unique contributions to team-based care. PMID- 26889944 TI - Protection or resection: BOD1L as a novel replication fork protection factor. AB - Replication stress, defined as the slowing or stalling of cellular DNA replication forks, represents a serious threat to genome stability. Numerous cellular pathways protect against replication stress and maintain genomic integrity. Among these, the Fanconi Anemia/homologous recombination pathways are critical for recognizing and repairing stalled replication forks. Members of these pathways play a vital role in protecting damaged forks from uncontrolled attack from cellular nucleases, which would otherwise render these irreparable. Recent studies have begun to shed light on the protective factors necessary to suppress nucleolytic over-processing of nascent DNA, and on the different cellular nucleases involved. Here, we review our recent identification of a novel fork protection factor, BOD1L, and discuss its role in preventing the processing of stalled replication forks within the context of current knowledge of the replication fork 'protectosome'. PMID- 26889947 TI - Mineralogical control on arsenic release during sediment-water interaction in abandoned mine wastes from the Argentina Puna. AB - The sulfide-rich residues of La Concordia mine, Argentina Puna, are accumulated in tailing dams that remained exposed to the weathering agents for almost 30years. In such period of time, a complex sequence of redox and dissolution/precipitation reactions occurred, leading to the gradual oxidation of the wastes and the formation of weathering profiles. The sources of arsenic in the wastes were analyzed by XRD and SEM/EDS analysis while a standardized sequential extraction procedure was followed to define solid As associations. In addition, the release of As during sediment-water interaction was analyzed in a period of 10months. The results indicate that primary As-bearing minerals are arsenian pyrite and polymetallic sulfides. As-jarosite and scarce arsenates are the only secondary As-bearing minerals identified by XRD and SEM/EDS. However, the rapid release (i.e., <1h) of arsenic from suspensions of the studied sediments in water, seems to be associated to the dissolution of highly soluble (hydrous)sulfates, as it was determined in samples of the efflorescences that cover the entire site. Contributions from the more abundant As-jarosite are also expected in longer periods of sediment-water interaction, due to its low rate of dissolution in acid and oxic conditions. Finally, near 30% of As remains adsorbed onto Fe (hydr)oxides thus representing a hazardous reservoir with the potential of mobilizing As into porewaters and streamwaters if the acidic and oxidizing conditions that predominate in the region are altered. PMID- 26889946 TI - A fundamental study on the dynamics of multiple biomarkers in mouse excisional wounds for wound age estimation. AB - Wound age estimation is a classic but still modern theme in forensic practice. More experiments on different types of wound are needed to further improve its accuracy. In this study, mouse skin excisional wounds were created to simulate dermal defective injury. The neutrophil and macrophage infiltration, fibroblast and fibrocyte accumulation as well as their myofibroblastic transformation were examined. In addition, some wound healing-related molecules, including IL-1beta, IL-6, TNF-alpha, IFN-gamma, MCP-1, CXCL12, VEGF-A, EGF, KGF, pro-col Ialpha2 and pro-col IIIalpha1, were quantified by Western blotting and real-time quantitative PCR. Neutrophils and macrophages profoundly infiltrated in the wound at 12 h-1 d and 3 d-10 d respectively. Fibroblasts and fibrocytes accumulated in the wound from 3 d, and transformed into contractile myofibroblasts from 5 d post injury. The transformation ratios of fibroblasts and fibrocytes were highest at 7 d-10 d and 10 d respectively (over 50%). MCP-1 and CXCL12 increased from 12 h to 5 d, and IL-1beta, TNF-alpha and pro-col IIIalpha1 up to 7 d. IL-6 and VEGF-A increased from 12 h to 1 d-10 d. Pro-col Ialpha2 increased from 7 d to 21 d. IFN gamma decreased from 12 h to 10 d. By comprehensive analysis of these factors from the perspective of morphometrics, protein and gene expressions, this study provided us with fundamental information for wound age estimation, especially in the wounds with full-thickness defection. PMID- 26889948 TI - What determines PCB concentrations in soils in rural and urban areas? Insights from a multi-media fate model for Switzerland as a case study. AB - Polychlorinated biphenyls (PCBs) are banned worldwide under the Stockholm Convention on Persistent Organic Pollutants. However, PCBs are still emitted in appreciable amounts from remaining primary sources in urban areas or landfills and are ubiquitous environmental contaminants, inter alia in soil and air. Concentrations of PCBs have been measured in various media by numerous studies worldwide. However, monitoring data do not always provide quantitative information about transport processes between different media, deposition fluxes to ground, or distribution of PCBs between environmental compartments. Also future trends in environmental contamination by PCBs cannot be predicted from monitoring data, but such information is highly relevant for decision-makers. Here, we present a new regionally resolved dynamic multimedia mass balance model for Switzerland to investigate the origin of PCBs in air and to investigate their long-term fate and mass balance in the environment. The model was validated with existing field data for PCBs. We find that advective inflow of PCBs from outside Switzerland into the atmospheric boundary layer is responsible for 80% of PCBs present in air in Switzerland, whereas Swiss emissions cause the remaining 20%. Furthermore, we show that the atmospheric deposition of the higher-chlorinated PCBs is dominated by particle-bound deposition, whereas the deposition of the lower-chlorinated PCBs is a combination of particle-bound and gaseous deposition. The volume fraction of particles in air is in both cases an important factor driving the deposition of PCBs to ground and, thus, contributing to the higher concentrations of PCBs generally observed in populated and polluted areas. Regional emissions influence the deposition fluxes only to a limited extent. We also find that secondary emissions from environmental reservoirs do not exceed primary emissions for all PCB congeners until at least 2036. Finally, we use our model to evaluate the effect of chemical regulation on future environmental contamination by PCBs. PMID- 26889950 TI - "Socioeconomic inequalities in children's accessibility to food retailing: Examining the roles of mobility and time". AB - Childhood overweight and obesity rates in Canada are at concerning levels, more apparently so for individuals of lower socioeconomic status (SES). Accessibility to food establishments likely influences patterns of food consumption, a contributor to body weight. Previous work has found that households living in lower income neighbourhoods tend to have greater geographical accessibility to unhealthy food establishments and lower accessibility to healthy food stores. This study contributes to the literature on neighbourhood inequalities in accessibility to healthy foods by explicitly focusing on children, an understudied population, and by incorporating mobility and time into metrics of accessibility. Accessibility to both healthy and unhealthy food retailing is measured within children's activity spaces using Road Network and Activity Location Buffering methods. Weekday vs. weekend accessibility to food establishments is then compared. The results suggest that children attending lower SES schools had almost two times the density of fast food establishments and marginally higher supermarket densities in their activity spaces. Children attending higher SES schools also had much larger activity spaces. All children had higher supermarket densities during weekdays than on weekend days. PMID- 26889949 TI - The 2008 financial crisis: Changes in social capital and its association with psychological wellbeing in the United Kingdom - A panel study. AB - The global financial crisis of 2008 was described by the IMF as the worst recession since the Great Depression. This historic event provided the backdrop to this United Kingdom (UK) longitudinal study of changes in associations between social capital and psychological wellbeing. Past longitudinal studies have reported that the presence of social capital may buffer against adverse mental health outcomes. This study adds to existing literature by employing data from the British Household Panel Survey and tracking the same individuals (N = 11,743) pre- and immediately post-crisis (years 2007-09). With longitudinal, multilevel logistic regression modelling, we aimed to compare the buffering effects of individual-level social capital (generalised trust and social participation) against worse psychological wellbeing (GHQ-12) during and immediately after the 2008 financial crisis. After comparing the same individuals over time, results showed that stocks of social capital (generalised trust) were significantly depleted across the UK during the crisis, from 40% trusting others in 2007 to 32% in 2008. Despite this drop, the buffering effect of trust against worse psychological wellbeing was pronounced in 2008; those not trusting had an increased risk of worse psychological wellbeing in 2008 compared with the previous year in fully adjusted models (OR = 1.49, 95% CI (1.34-1.65). Levels of active participation increased across the timeframe of this study but were not associated with psychological health. From our empirical evidence, decision makers should be made aware of how events such as the crisis (and the measures taken to counter its effects) could negatively impact on a Nation's trust levels. Furthermore, past research implies that the positive effects of trust on psychological wellbeing evident in this study may only be short-term; therefore, decision makers should also prioritise policies that restore trust levels to improve the psychological wellbeing of the population. PMID- 26889951 TI - Employment insecurity and mental health during the economic recession: An analysis of the young adult labour force in Italy. AB - BACKGROUND AND OBJECTIVE: A growing body of scientific literature highlights the negative consequences of employment insecurity on several life domains. This study focuses on the young adult labour force in Italy, investigating the relationship between employment insecurity and mental health and whether this has changed after years of economic downturn. It enhances understanding by addressing differences in mental health according to several employment characteristics; and by exploring the role of respondents' economic situation and educational level. DATA AND METHODS: Data from a large-scale, nationally representative health survey are used to estimate the relationship between employment insecurity and the Mental Health Inventory (MHI), by means of multiple linear regressions. RESULTS AND CONCLUSIONS: The study demonstrates that employment insecurity is associated with poorer mental health. Moreover, neither temporary workers nor unemployed individuals are a homogeneous group. Previous job experience is important in differentiating the mental health risks of unemployed individuals; and the effects on mental health vary according to occupational status and to the amount of time spent in a condition of insecurity. Further, the experience of financial difficulties partly explains the relationship between employment insecurity and mental health; and different mental health outcomes depend on respondents' educational level. Lastly, the risks of reporting poorer mental health were higher in 2013 than in 2005. PMID- 26889952 TI - Polio vaccine hesitancy in the networks and neighborhoods of Malegaon, India. AB - OBJECTIVES: Eradication and control of childhood diseases through immunization can only work if parents allow their children to be vaccinated. To learn about social network factors associated with polio vaccine hesitancy, we investigated social and spatial clustering of households by their vaccine acceptance status in Malegaon, India, an area known for vaccine refusal and repeated detection of polio cases. METHODS: We interviewed family heads from 2462 households in 25 neighborhoods in July 2012 and constructed social networks based on advice seeking from other households. We restricted our main analyses to surveyed households for which we also had data on whether they accepted the polio vaccine for their eligible children or not. RESULTS: Data from 2452 households was retained and these households made 2012 nominations to 830 households. Vaccine refusing households had fewer outgoing ties than vaccine-accepting households. After excluding 24 isolated households, vaccine-refusing households had 189% more nominations to other vaccine-refusing households (93% more in the largest component of the network) compared to vaccine-accepting households, revealing that vaccine-refusing households cluster in the social network. Since roughly half of all ties connect households within neighborhoods, vaccine-refusing clusters lie in spatially localized "pockets". CONCLUSIONS: The social (and spatial) clustering of vaccine-refusing households could be leveraged to tailor communication strategies to improve vaccine acceptance and community perceptions of immunization programs for polio and other vaccine-preventable diseases. PMID- 26889954 TI - Tissue Distribution and Transfer to Eggs of Ingested alpha-Hexabromocyclododecane (alpha-HBCDD) in Laying Hens (Gallus domesticus). AB - The aim of the current study was to describe the fate of ingested alpha hexabromocyclododecane (alpha-HBCDD) in laying hens. Individuals were exposed to two dietary concentrations of alpha-HBCDD (50 and 5 ng g(-1) feed) for 18 or 11 weeks followed by a 7-week decontamination period. The results show that no isomerization of alpha- to beta- or gamma-HBCDD forms occurred, whereas OH-HBCDD was identified as a product of alpha-HBCDD metabolism. Irrespective of the level of feed contamination, estimates of steady-state accumulation ratios were 5.2, 3.6, and 9.2 and half-lives were estimated at 17.4, 22.8, and 35.3 days in egg yolk, liver tissue, and abdominal fat, respectively. The steady-state carry-over rate to eggs was 22.9%. Thus, alpha-HBCDD ingested by laying hens is readily transferred to eggs and significantly accumulates in adipose tissue. PMID- 26889955 TI - Reorientational Relaxation of Small Solutes in Viscoelastic Liquids. AB - The reorientational relaxation times of some small aromatic solutes are determined with nuclear magnetic resonance spectroscopy and time-resolved fluorescence anisotropy measurements in various solvents that exhibit viscoelasticity in the megahertz region. All the reorientational relaxation times in viscoelastic liquids are shorter than those predicted by the hydrodynamic Stokes-Einstein-Debye (SED) relation using the steady-state shear viscosity. The deviation from the SED relation becomes larger in solvents whose shear relaxation is slower. When the reorientational relaxation times in a solvent are compared, the deviation from the SED relation tends to decrease when the reorientational relaxation time increases. From a comparison with the shear relaxation spectra, it is demonstrated that the deviation from the SED relation can be ascribed to the effective reduction of the viscous friction on fast reorientation, reflecting the decrease in shear viscosity with increasing frequency. PMID- 26889953 TI - Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities. AB - The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas. Here, we report that mouse embryonic fibroblasts null for the Hmga1 gene show downregulation of Bub1, Bub1b, Mad2l1 and Ttk SAC genes, and present several features of chromosomal instability, such as nuclear abnormalities, binucleation, micronuclei and karyotypic alterations. Interestingky, also MEFs carrying only one impaired Hmga1 allele present karyotypic alterations. These results indicate that HMGA1 proteins regulate SAC genes expression and, thereby, genomic stability also in embryonic cells. PMID- 26889956 TI - The Alga Ochromonas danica Produces Bromosulfolipids. AB - Many halogenases interchangeably incorporate chlorine and bromine into organic molecules. On the basis of an unsubstantiated report that the alga Ochromonas danica, a prodigious producer of chlorosulfolipids, was able to produce bromosulfolipids, we have investigated the promiscuity of its halogenases toward bromine incorporation. We have found that bromosulfolipids are produced with the exact positional and stereochemical selectivity as in the chlorosulfolipid danicalipin A when this alga is grown under modified conditions containing excess bromide ion. PMID- 26889957 TI - Investigation of the Na Intercalation Mechanism into Nanosized V2O5/C Composite Cathode Material for Na-Ion Batteries. AB - There is a significant interest to develop high-performance and cost-effective electrode materials for next-generation sodium ion batteries. Herein, we report a facile synthesis method for nanosized V2O5/C composite cathodes and their electrochemical performance as well as energy storage mechanism. The composite exhibits a discharge capacity of 255 mAh g(-1) at a current density of 0.05 C, which surpasses that of previously reported layered oxide materials. Furthermore, the electrode shows good rate capability; discharge capacity of 160 mAh g(-1) at a current density of 1 C. The reaction mechanism of V2O5 upon sodium insertion/extraction is investigated using ex situ X-ray diffraction (XRD) and synchrotron based near edge X-ray absorption fine structure (NEXAFS) spectroscopy. Ex situ XRD result of the fully discharged state reveals the appearance of NaV2O5 as a major phase with minor Na2V2O5 phase. Upon insertion of sodium into the array of parallel ladders of V2O5, it was confirmed that lattice parameter of c is increased by 9.09%, corresponding to the increase in the unit cell volume of 9.2%. NEXAFS results suggest that the charge compensation during de/sodiation process accompanied by the reversible changes in the oxidation state of vanadium (V(4+) <-> V(5+)). PMID- 26889959 TI - Human Lymphadenopathy Caused by Ratborne Bartonella, Tbilisi, Georgia. AB - Lymphadenopathy and fever that developed in a woman in Tbilisi, Georgia, most likely were caused by a ratborne Bartonella strain related B. tribocorum and B. elizabethae. The finding suggests that this Bartonella strain could be spread by infected rats and represents a potential human risk. PMID- 26889960 TI - Novel Reassortant Avian Influenza A(H5N1) Virus in Human, Southern Vietnam, 2014. PMID- 26889961 TI - Far East Scarlet-Like Fever Caused by a Few Related Genotypes of Yersinia pseudotuberculosis, Russia. AB - We used multivirulence locus sequence typing to analyze 68 Yersinia pseudotuberculosis isolates from patients in Russia during 1973-2014, including 41 isolates from patients with Far East scarlet-like fever. Four genotypes were found responsible, with 1 being especially prevalent. Evolutionary analysis suggests that epidemiologic advantages could cause this genotype's dominance. PMID- 26889962 TI - Development and application of monoclonal antibodies for detection and analysis of aquareoviruses. AB - Monoclonal antibodies (mAbs) play an important role in detection of aquareoviruses. Three mAbs against grass carp reovirus (GCRV) were prepared. Isotyping revealed that all three mAbs were of subclass IgG2b. Western blot assay showed that all three mAbs reacted with GCRV 69 kDa protein (the putative VP5). In addition to the 69 kDa protein of GCRV, mAb 4B6 also recognize a 54 kDa protein. All three mAbs were used for detecting aquareovirus by Western blot assay and indirect immunofluorescence assay (IFA). All of them reacted with GCRV, and mAb 4A3 could also react with turbot Scophthalmus maximus reovirus (SMReV) and largemouth bass Microptererus salmonides reovirus (MsReV). Viral antigens were only observed in the cytoplasm of infected cells. Finally, syncytia formation was observed with light microscopy and fluorescence microscopy using fluorescein labelled 4A3 mAb at various times post-infection. Syncytia were observed at 36 hr post-infection (hpi) by light microscopy and at 12 hpi by fluorescence microscopy. The immunofluorescence based assay allowed earlier detection of virus than observation of virus-induced cytopathic effect (CPE) assay in inoculated cell cultures. The sensitivity and specificity of these mAbs may be useful for diagnosis and monitoring of aquareoviruses. PMID- 26889963 TI - Adherence to treatment and monitoring tools: what's new. AB - Asthma is a serious global health problem affecting all age groups, with global prevalence. Although controller medications are usually highly effective asthma treatments, patient adherence remains poor, and under-use is associated with greater health resource use, morbidity, and mortality. Up to 70-80% of patients cannot use their inhaler correctly, and similar proportions of health professionals are unable to demonstrate correct use. A recent paper of Foster and colleagues explored the effectiveness of 2 briefs GPs delivered intervention in improving adherence to asthma treatment and diseases control in patients with uncontrolled moderate/severe persistent asthma, in real-community setting. The results suggested that inhaler reminders may represent an effective strategy for improving adherence in primary care compared with a behavioral intervention or usual care, although this may not be reflected in differences in levels of asthma control. Studies in larger population are needed in order to test the efficacy of available technology on asthma outcomes in all age stages. PMID- 26889964 TI - Asthma in pregnancy: one more piece of the puzzle. AB - Asthma is the most common respiratory disorder complicating pregnancy, and is associated with a range of adverse maternal and perinatal outcomes. There is strong evidence however, that the adequate control of asthma can improve health outcomes for mothers and their babies. Despite known risks of poorly controlled asthma during pregnancy, a large proportion of women have sub- optimal asthma control, due to concerns surrounding risks of pharmacological agents, and uncertainties regarding the effectiveness and safety of different management strategies. A recent retrospective study showed that step up therapy with low dose ICS/LABA or high dose ICS presents the same risk profile in terms of major congenital malformations. These results are consistent with asthma management guidelines and provide scientific evidence to help physicians and mothers make evidence-based treatment decisions during pregnancy, particularly when a step up to higher doses of ICS or addition of a LABA is required. These reassuring results should encourage women to continue their asthma medications when required to control their asthma during pregnancy and increase the likelihood of healthy pregnancies and newborns. This commentary focuses on some critical issues of this recent work and to the need of future study to evaluate the safety during pregnancy of novel molecules recently introduced for asthma treatment. PMID- 26889958 TI - High-Density Lipoproteins: Nature's Multifunctional Nanoparticles. AB - High-density lipoproteins (HDL) are endogenous nanoparticles involved in the transport and metabolism of cholesterol, phospholipids, and triglycerides. HDL is well-known as the "good" cholesterol because it not only removes excess cholesterol from atherosclerotic plaques but also has anti-inflammatory and antioxidative properties, which protect the cardiovascular system. Circulating HDL also transports endogenous proteins, vitamins, hormones, and microRNA to various organs. Compared with other synthetic nanocarriers, such as liposomes, micelles, and inorganic and polymeric nanoparticles, HDL has unique features that allow them to deliver cargo to specific targets more efficiently. These attributes include their ultrasmall size (8-12 nm in diameter), high tolerability in humans (up to 8 g of protein per infusion), long circulating half-life (12-24 h), and intrinsic targeting properties to different recipient cells. Various recombinant ApoA proteins and ApoA mimetic peptides have been recently developed for the preparation of reconstituted HDL that exhibits properties similar to those of endogenous HDL and has a potential for industrial scale-up. In this review, we will summarize (a) clinical pharmacokinetics and safety of reconstituted HDL products, (b) comparison of HDL with inorganic and other organic nanoparticles, PMID- 26889965 TI - Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice. AB - PURPOSE: Transcranial low-level light therapy (LLLT) has gained interest as a non invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. METHODS: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. RESULTS: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF kappaB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. CONCLUSIONS: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption. PMID- 26889966 TI - The dynamic motor imagery of locomotion is task-dependent in patients with stroke. AB - PURPOSE: Recently, Motor Imagery (MI) has been associated with the execution of movements miming in part the mentally represented action (dynamic MI, dMI). Preliminary studies have reported as dMI may improve trainings in sport, with imagery timing close to the physical execution one. This study was aimed to investigate time and spatial parameters of dMI with actual locomotion in people with stroke. METHODS: Twelve patients (stroke group, SG) were compared with twelve healthy elderly (elderly group, EG) and twenty young adults (young group, YG). Subjects performed mental representations of different walking (forward, FW; lateral, LW, backward, BW), accompanied or not by movements imitating walking (dMI and static MI, sMI). Then, they performed actual locomotion (AL). Outcome measures were related to the time and the number of steps spent for completing the tasks for all the given locomotor conditions. RESULTS: Significant differences were found in patients with respect to healthy subjects, with time in sMI significantly shorter than in dMI (p < 0.004) and AL (p < 0.002), but not between dMI and AL in FW (p = 0.806). In patients, times obtained in sMI and dMI was significantly shorter with respect to those of AL in LW and BW. Patients performed imagery tasks with similar times in all locomotion. Healthy groups did not reveal differences among tasks in BW, while significant differences were found in LW. Analogous results were found in terms of number of performed steps. CONCLUSIONS: In patients with stroke, a spatiotemporal functional equivalence with AL was found only for dMI, and not for sMI, in forward walking. This could be due to familiarity with this task. These results might have implications for the rehabilitative techniques based on MI. PMID- 26889967 TI - Ultrasonic vocalization in murine experimental stroke: A mechanistic model of aphasia. AB - PURPOSE: Approximately one-fourth of stroke survivors are aphasic. Speech therapy is the main treatment approach but leaves most patients with chronic disability. Attempts to improve this situation are hampered by a lack of mechanistic understanding of the disability and treatments, reflecting the neglect of this impairment modality in pre-clinical research. Accordingly, we devised a novel murine model of speech-related impairment after stroke to investigate the role of language- and plasticity-associated molecules. Rodents communicate socially with ultrasonic vocalizations (USVs), conveying semantic and semiotic information with complex frequency modulated "songs" and alarm calls. METHODS: Transient focal cerebral ischemia was induced in male C57BL6 mice via either 30 or 45 minutes of reversible right MCAO using the intraluminal filament technique. Nine days post operatively brains are stained with TTC and analyzed for infarct volume. For behavioral measures health scores are taken (days 1-4), cylinder tests and USV recordings performed at days 3 and 7 post operatively. Real time PCR was performed at 24 and 48 hour and 7 day time points to quantify mRNA expression of communication-related genes (Foxp2, Foxp1, Srpx2, Cntnap2 and Gapdh). Immunohistochemistry was performed to localize FOXP2 protein. RESULTS: After middle cerebral artery occlusion of either 30 or 45 minutes duration, mice demonstrate profoundly impaired socially evoked USVs. In addition, there is suppression of the language-associated transcription factor, Forkhead box protein 2 (Foxp2), and its downstream binding partner, contactin-associated protein 2 (Cntnap2). CONCLUSION: These findings set a foundation for further studies of mechanisms and novel treatment strategies for post-stroke vocalization impairments. PMID- 26889968 TI - L1.2, the zebrafish paralog of L1.1 and ortholog of the mammalian cell adhesion molecule L1 contributes to spinal cord regeneration in adult zebrafish. AB - PURPOSE: The aim of the study was to investigate the functional role of L1.2, the zebrafish paralog of L1.1 and ortholog of mammalian L1CAM in adult zebrafish spinal cord regeneration after injury. L1CAM and L1.1 have shown beneficial features in ameliorating nervous system dysfunctions in different experimental paradigms. It thus deemed important to characterize the L1.2 member of the L1CAM family, the functions of which are unknown. METHODS: Spinal cord transection of adult zebrafish, application of anti-sense morpholino to reduce L1.2 expression, qPCR, immunohistology, immunoblotting, in situ hybridization, retrograde tracing, anterograde tracing. RESULTS: Similar to L1.1, L1.2 expression in adult zebrafish is upregulated after spinal cord transection. By co-localization of in situ hybridization and immunohistology, L1.2 is expressed in neurons and, in contrast to L1.1, it is also expressed in GFAP-immunoreactive glia. Reducing L1.2 protein levels leads to impaired locomotor recovery and reduction of regrowth of severed descending axons from a brain stem nucleus which is composed of neurons innately capable of axonal regrowth. CONCLUSIONS: Our findings support the speculation that paralogs of duplicated genes can exert similar functions and may thus represent an advantage over other species that do not carry duplicated genes. PMID- 26889971 TI - Definition of giant ventral hernias: Development of standardization through a practice survey. AB - BACKGROUND: Giant ventral hernias represent a real handicap for patients and constitute a challenge for surgeons. European Hernia Society classification defines all ventral hernia over 10 cm in the same group. However, this group represents different clinical entities with numerous therapeutic possibilities, and no standardized recommendation has been made. The objective of our work was to define consensual criteria that define giant ventral hernias requiring specific management and determine management modalities. METHODS: A national survey consisting of 21 questions was proposed through a secure, anonymous internet interface and on a voluntary basis to all surgeons practising in France involved in care of patients affected by giant ventral hernias. RESULTS: For more than 68% of respondents, loss of domain and a hernia volume greater than 30% of abdominal volume were mandatory to define giant ventral hernias. Pre-operative screening should include abdominal CT scan, functional respiratory exploration, and a cardiology consultation for 98%, 71% and 50% of the respondents respectively. Respiratory and cutaneous preparations were systematically proposed before surgery by 91% and 56% of respondents. Regarding surgical techniques, none has gained the support of the majority of respondents. However, 71% of respondents use a non-resorbable mesh in retro muscular position for more than 70% of their patients treated for giant ventral hernias. CONCLUSION: Giant ventral hernias could be defined as ventral hernia larger than 10 cm with loss of domain. A specific management is advocated. PMID- 26889970 TI - Experience of damage control trauma laparotomy in a limited resource healthcare setting: A retrospective Cohort Study. AB - INTRODUCTION: Damage control surgery (DCS) is an established option for managing severely injured trauma patients. However, its role in the management of similar patients in the developing world is debatable. The purpose of this study is to describe characteristics and outcomes of patients undergoing DCS. METHODS: All trauma patients requiring laparotomies from 1996 to 2011 at a tertiary care hospital in South Asia were reviewed. DCS was defined in a patient who underwent a truncated laparotomy where the fascia was primarily left open, with the intention of physiological optimization in the Intensive Care Unit, followed by definitive surgery. The primary outcome was in-hospital mortality. Multivariate logistic regression was used to determine the independent predictors of mortality after adjustment for potential confounders. RESULTS: Of 258 patients, 47 underwent DCS. 40% patients were transferred from other hospitals. The time between injury and operation was 152 minutes (IQR: 90-330). Intra-operative laboratory parameters revealed a median pH of 7.16 (IQR: 7.10-7.27), median temperature of 34.7 (IQR: 34.0-35.4) and median PT of 15.9 (IQR: 12.4-21.2). 55% of the patients survived to discharge from hospital. Of those who died, 86% died before the first take back operation. Packed red blood cell transfusion and vascular injury were independently associated with mortality. DISCUSSION: Damage control surgery is feasible in developing countries, with more than 50% survival reported at one hospital. Future research should focus on critical care management. CONCLUSION: Damage Control trauma laparotomy is feasible in tertiary care hospitals with multidisciplinary trauma teams in lesser-developed countries. PMID- 26889969 TI - An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication. AB - Prenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal = 1,740) revealed no epigenome-wide (meta P <1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P <1.00e-04) indicated an over representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P <1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies. PMID- 26889972 TI - Current status of surgical treatment of gastric cancer in the era of minimally invasive surgery in China: Opportunity and challenge. AB - Gastric cancer is one of the most common cancers in China. In the past decade, with the developments in surgical instruments and technologies, minimally invasive surgery has rapidly become an accepted treatment for gastric cancer in China. Many Chinese surgeons and researchers have contributed to the rapid evolution of minimally invasive surgery for gastric cancer. Their efforts have transformed into unique laparoscopic technique, workshops, academic communications, education and international communications in China. Meanwhile, many retrospective comparative trials and randomized controlled trials have revealed the advantages in minimally invasive surgery for gastric cancer. However, multicenter randomized controlled trials are still needed to delineate significantly quantifiable differences between laparoscopic and open gastrectomy. With more and more experience has accumulated, laparoscopic gastrectomy has been performed on older and overweight patients. Moreover, advanced minimally invasive techniques, such as modified laparoscopic spleen-preserving splenic hilum lymphadenectomy, various laparoscopic gastric reconstruction methods and robotic gastrectomy have been developed. It seems that China owns the potential to keep up with her neighbor, Japan and Korea, to become one of leading countries utilizing minimally invasive surgery for gastric cancer. PMID- 26889973 TI - Clinical impact of mutation fraction in epidermal growth factor receptor mutation positive NSCLC patients. AB - BACKGROUND: We examined clinical outcomes in a population-based cohort of EGFR mutant advanced NSCLC patients, exploring the potential role of factors including tumour EGFR mutation fraction and cellularity in predicting outcomes. METHODS: A cohort of patients with EGFR mutant advanced NSCLC was identified (N =2 93); clinical outcomes, pathologic and treatment details were collected. Tumour response was determined from radiology and clinical notes. Association between demographic and pathologic variables EGFR TKI response, time to treatment failure (TTF) and overall survival (OS) was examined using logistic regression and proportional hazards regression. EGFR TKI response rates were summarised by percent mutation fraction to explore their association. RESULTS: Higher mutation fraction was associated with greater EGFR TKI response rate (odds ratio 1.58, 95% CI = 1.21-2.07, P = 0.0008), longer TTF (hazard ratio 0.80, 95% CI = 0.68-0.92, P = 0.003) and better OS (hazard ratio 0.81, 95% CI = 0.67-0.99, P = 0.04). However, even in patients with ? 5% mutation fraction, response rate was 34%. Females had longer TTF (P = 0.02). CONCLUSIONS: EGFR mutation fraction in tumour samples was significantly associated with response, TTF and OS. Despite this, no lower level of mutation fraction was detected for which EGFR TKI should be withheld in those with activating EGFR mutations. PMID- 26889974 TI - Derived neutrophil lymphocyte ratio is predictive of survival from intermittent therapy in advanced colorectal cancer: a post hoc analysis of the MRC COIN study. AB - BACKGROUND: The phase III COntinuous or INtermittent (COIN) trial failed to show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in overall survival (OS). The present analysis evaluated whether the derived neutrophil to lymphocyte ratio (dNLR) could predict the effect of intermittent vs continuous chemotherapy on OS in patients with advanced colorectal cancer. METHODS: A post hoc exploratory analysis of COIN arms A and C was performed. Landmark analysis was conducted on all patients with available WBC and neutrophils data. The dNLR was calculated using a formula which has previously demonstrated predictive power in cancer patients: dNLR = ANC/(WBC ANC). A high dNLR was defined using a cut-off value of ? 2.22. Derived neutrophil to lymphocyte ratio was then correlated with clinical outcomes. Survival curves were generated based on dNLR using the Kaplan-Meier method. Comparison between groups was performed using Cox regression. RESULTS: A total of 1630 patients were assigned to the continuous (N = 815) or intermittent (N = 815) arms. There was a strong association between dNLR level and OS. The median survival times in the ITT population were 18.6 months and 12.5 months for patients with low and high dNLR, respectively (HR = 1.70; 95% CI = 1.52-1.90; P < 0.001). The estimate of the hazard ratio did not alter substantially (HR = 1.54) after adjusting for treatment, tumour status, number of metastatic sites, alkaline phosphate and platelet count. CONCLUSIONS: Derived neutrophil to lymphocyte ratio is strongly prognostic for survival in the COIN intermittent vs continuous treatment arms. Derived neutrophil to lymphocyte ratio does not predict for detrimental survival in patients treated with intermittent therapy. PMID- 26889976 TI - A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma. AB - BACKGROUND: We aimed to identify prognostic blood biomarkers using proteomics based approaches in malignant pleural mesothelioma (MPM). METHODS: Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n=97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts. RESULTS: Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P=0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P=0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC. CONCLUSIONS: Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC. PMID- 26889977 TI - Ectopic expression of the chemokine CXCL17 in colon cancer cells. AB - BACKGROUND: The novel chemokine CXCL17 acts as chemoattractant for monocytes, macrophages and dendritic cells. CXCL17 also has a role in angiogenesis of importance for tumour development. METHODS: Expression of CXCL17, CXCL10, CXCL9 and CCL2 was assessed in primary colon cancer tumours, colon carcinoma cell lines and normal colon tissue at mRNA and protein levels by real-time qRT-PCR, immunohistochemistry, two-colour immunofluorescence and immunomorphometry. RESULTS: CXCL17 mRNA was expressed at 8000 times higher levels in primary tumours than in normal colon (P < 0.0001). CXCL17 protein was seen in 17.2% of cells in tumours as compared with 0.07% in normal colon (P = 0.0002). CXCL10, CXCL9 and CCL2 mRNAs were elevated in tumours but did not reach the levels of CXCL17. CXCL17 and CCL2 mRNA levels were significantly correlated in tumours. Concordant with the mRNA results, CXCL10- and CXCL9-positive cells were detected in tumour tissue, but at significantly lower numbers than CXCL17. Two-colour immunofluorescence and single-colour staining of consecutive sections for CXCL17 and the epithelial cell markers carcinoembryonic antigen and BerEP4 demonstrated that colon carcinoma tumour cells indeed expressed CXCL17. CONCLUSIONS: CXCL17 is ectopically expressed in primary colon cancer tumours. As CXCL17 enhances angiogenesis and attracts immune cells, its expression could be informative for prognosis in colon cancer patients. PMID- 26889975 TI - Therapeutic interactions of autophagy with radiation and temozolomide in glioblastoma: evidence and issues to resolve. AB - Glioblastoma is a unique model of non-metastasising disease that kills the vast majority of patients through local growth, despite surgery and local irradiation. Glioblastoma cells are resistant to apoptotic stimuli, and their death occurs through autophagy. This review aims to critically present our knowledge regarding the autophagic response of glioblastoma cells to radiation and temozolomide (TMZ) and to delineate eventual research directions to follow, in the quest of improving the curability of this incurable, as yet, disease. Radiation and TMZ interfere with the autophagic machinery, but whether cell response is driven to autophagy flux acceleration or blockage is disputable and may depend on both cell individuality and radiotherapy fractionation or TMZ schedules. Potent agents that block autophagy at an early phase of initiation or at a late phase of autolysosomal fusion are available aside to agents that induce functional autophagy, or even demethylating agents that may unblock the function of autophagy-initiating genes in a subset of tumours. All these create a maze, which if properly investigated can open new insights for the application of novel radio and chemosensitising policies, exploiting the autophagic pathways that glioblastomas use to escape death. PMID- 26889979 TI - Relationship between ambient ultraviolet radiation and Hodgkin lymphoma subtypes in the United States. AB - BACKGROUND: There are few modifiable risk factors for Hodgkin lymphoma (HL), the most common cancer among young adults in Western populations. Some studies have found a reduced risk with exposure to ultraviolet radiation (UVR), but findings have been inconsistent and limited to HL as a group or the most common subtypes. METHODS: We evaluated UVR and incidence of HL subtypes using data from 15 population-based cancer registries in the United States from 2001 to 2010 (n=20 021). Ground-based ambient UVR estimates were linked to county of diagnosis. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression models adjusted for age, sex, race/ethnicity, diagnosis year, and registry. RESULTS: Hodgkin lymphoma incidence was lower in the highest UVR quintile for nodular sclerosis (IRR=0.84, 95% CI=0.75-0.96, P-trend<0.01), mixed cellularity/lymphocyte-depleted (IRR=0.66, 95% CI=0.51-0.86, P-trend=0.11), lymphocyte-rich (IRR=0.71, 95% CI=0.57-0.88, P trend<0.01), and nodular lymphocyte predominant HL (IRR=0.74, 95% CI=0.56-0.97, P trend<0.01), but 'not otherwise specified' HL (IRR=1.19, 95% CI=0.96-1.47, P trend=0.11). CONCLUSIONS: This is the largest study of UVR and HL subtypes covering a wide range of UVR levels; however, we lack information on personal UVR and other individual risk factors. These findings support an inverse association between UVR and HL. PMID- 26889978 TI - Long working hours and cancer risk: a multi-cohort study. AB - BACKGROUND: Working longer than the maximum recommended hours is associated with an increased risk of cardiovascular disease, but the relationship of excess working hours with incident cancer is unclear. METHODS: This multi-cohort study examined the association between working hours and cancer risk in 116 462 men and women who were free of cancer at baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers; weekly working hours were self-reported. RESULTS: During median follow-up of 10.8 years, 4371 participants developed cancer (n colorectal cancer: 393; n lung cancer: 247; n breast cancer: 833; and n prostate cancer: 534). We found no clear evidence for an association between working hours and the overall cancer risk. Working hours were also unrelated the risk of incident colorectal, lung or prostate cancers. Working ?55 h per week was associated with 1.60-fold (95% confidence interval 1.12-2.29) increase in female breast cancer risk independently of age, socioeconomic position, shift- and night-time work and lifestyle factors, but this observation may have been influenced by residual confounding from parity. CONCLUSIONS: Our findings suggest that working long hours is unrelated to the overall cancer risk or the risk of lung, colorectal or prostate cancers. The observed association with breast cancer would warrant further research. PMID- 26889981 TI - Overexpression of Cdc20 in clinically localized prostate cancer: Relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy. AB - OBJECTIVES: This study was aimed to explore Cdc20 expression and its correlation with clinicopathological characteristics and biochemical recurrence (BCR) after laparoscopic radical prostatectomy (LRP) in clinically localized prostate cancer (PCa). METHODS: Cdc20 expression was examined by immunohistochemistry in 166 cases, including 60 cases of benign hyperplasia of prostate (BPH) patients treated by transurethral resection and 106 cases of consecutive PCa patients treated by LRP without neoadjuvant therapy in a single Chinese institution. The correlation with clinicopathological features and the predictive value for BCR were statistically analyzed. RESULTS: Cdc20 expression was detected in 52 (86.7%) BPH and 97 (91.5%) PCa samples, which was statistically insignificant (P= 0.675). The rate of patients with high expression of Cdc20 was 21.7% in BPH and 37.7% in PCa (P= 0.033). A correlation was revealed between Cdc20 expression and postoperative Gleason scores (P= 0.046), positive surgical margin (P< 0.001). BCR free survival was significantly lower in patients with high Cdc20 expression than those with low Cdc20 expression (P= 0.018). Univariate analysis indicated pTstage, post operative Gleason score, seminal vesicle invasion, lymph node invasion, surgical margin and Cdc20 expression significantly influenced BCR. Multivariate analysis revealed that postoperative Gleason score, seminal vesicle invasion, lymph node invasion, surgical margin and Cdc20 expression were independent predictors for BCR. After stratified by Gleason score and surgical margin status, Cdc20 expression and lymph node invasion remained significant in Cox regression analysis. CONCLUSIONS: Overexpression of Cdc20 may serve as an independent predictor for BCR in patients of clinically localized PCa undergoing LRP without neoadjuvant therapy. PMID- 26889980 TI - Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas. AB - BACKGROUND: Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. METHODS: We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. RESULTS: We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). CONCLUSIONS: We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically. PMID- 26889982 TI - An insertion/deletion polymorphism in the interleukin-1A 3'untranslated region confers risk for gastric cancer. AB - OBJECTIVE: The aim of the study was to evaluate whether the insertion/deletion polymorphism (rs3783553) locating in the 3' untranslated region (3'UTRs) of IL-1A was related to the risk of gastric cancer (GC) in a Chinese population and explore the possible molecular mechanism. METHODS: Genomic DNA was extracted from peripheral venous blood of 519 GC patients and 536 healthy control individuals. The IL-1A rs3783553 polymorphism was genotyped by using a polymerase chain reaction assay. The vectors containing the insertion or deletion allele were constructed, and luciferase assay was used to detect the effect of the polymorphism on the transcriptional activity of IL-1A. RESULTS: Strong evidence of association was observed between the IL-1A rs3783553 polymorphism and susceptibility to GC in the study. In addition, the 'TTCA' insertion allele of rs3783553 disrupts the binding site for miR-122 and miR-378, thereby increasing transcription of IL-1alpha in vitro. CONCLUSION: These findings suggest that functional polymorphism rs3783553 in IL-1A could contribute to GC susceptibility, possibly or at least partially through affecting the transcriptional activity of IL-1A. PMID- 26889983 TI - MicroRNAs contribution in tumor microenvironment of esophageal cancer. AB - BACKGROUND: miRNAs have recently been implicated in tumor's microenvironment remodeling and tumor-stromal cells interactions. We have previously reported a signaling role for miR-21, as a secretory molecule released by cancer associated fibroblasts (CAF) adjacent to esophagus tumor cells. OBJECTIVE: To discover other potential signaling miRNAs, we employed a co-culture system of esophageal cancer cell line and normal fibroblasts to mimic the tumor microenvironment. METHODS: We measured the expression profile of secretory miRNAs in the conditioned media (CM) of our co-culture system using a panel PCR array. We used pathway enrichment analysis to define potential pathways regulated by these miRNAs. Then using ultracentrifugation, we purified exosomes secreted to the CM of co-cultured cell lines and evaluated exosomal secretion of these miRNAs. RESULTS: We found 18 miRNAs which were significantly up/down-regulated in the CM of co-culture system. Pathways related to cell adhesion, endocytosis and cell junctions were among the enriched pathways that might be related to CAF phenotype and tumor progression. Moreover, we detected higher exosomal levels of miR-33a and miR-326 in the purified exosomes both in co-cultured and untreated CM. So, these miRNAs are mainly secreted into the CM by means of exosomes. CONCLUSIONS: Briefly, our data shed more light on the role of CAFs through secretion of miRNAs within tumor microenvironment and propose novel therapeutic targets for esophageal and probably other cancer types. PMID- 26889984 TI - Novel mutations of PIK3CA gene in head and neck squamous cell carcinoma. AB - BACKGROUND: HNSCC is the sixth most common human cancer globally. In Saudi Arabia, HNSCC accounts for seven percent of all newly diagnosed cancer cases. The PIK3CA is one of the most commonly mutated oncogene in human malignancies, including HNSCC. OBJECTIVE: The objective of this study is to identify mutations in exon 9 and exon 20 of the PIK3CA gene among Saudi HNSCC patients, determine the frequency of these mutations and correlate with clinical and pathological findings. METHODS: Histopathologically confirmed paraffin embedded HNSCC tumor tissues from 48 patients were obtained. Capillary sequencing method was used to sequence exons 9 and 20 of the PIK3CA gene. Concurrently, the expression analysis of the PIK3CA and PTEN genes were performed using real-time PCR. RESULTS: Sixty percent of the samples studied were of pharyngeal cancer. A total of seven mutations were identified in exons 9 and 20 of the PIK3CA gene in 14 HNSCC tumor tissue specimens. The seven mutations encompassed one hot spot mutation E542K, a common mutation T1025T and the five novel mutation comprising three missense and two silent mutations. Interestingly, eight out of the 14 samples with a mutation were of patients with pharyngeal cancer. CONCLUSION: PIK3CA gene plays a crucial role in carcinogenesis in general and HNSCC in particular. The identification of five novel mutations suggest that Saudis may have different frequencies of somatic genetic alterations that may influence HNSCC compared to other populations. PMID- 26889985 TI - Sacroiliac Joint Pain and Its Treatment. AB - The sacroiliac joint (SIJ) as a source of symptoms has been controversial; however, as knowledge about the joint increased, its role as a pain generator in patients complaining of symptoms that are often attributed to spinal pathology has become better appreciated. The literature reports that the SIJ is the pain origin in as many as 30% of patients presenting with low back pain. Clinically, the SIJ can be challenging to evaluate; however, assessing pain location, patient posture/movement, and provocative manual testing are useful in making the presumptive diagnosis of SIJ disruption. The most definitive evaluation is image guided injection of anesthetic solutions into the joint which is diagnostic if there is at least 75% symptom relief acutely. Treatment begins with nonoperative intervention including physical therapy and/or chiropractic care. If these fail, the next option is generally radiofrequency denervation (rhizotomy) of the joint. If this does not provide adequate relief, surgical intervention, in the form of minimally invasive SIJ fusion may be considered. The literature increasingly supports favorable results of SIJ fusion in appropriately selected patients. The purpose of this review is to provide an overview of the current literature on the SIJ, with focus on its surgical treatment. PMID- 26889986 TI - Obtuse-angled Laminotomy as a Modification of Multilevel Laminectomy for Spinal Cord Decompression. AB - The purpose of this note is to describe an obtuse-angled laminotomy of C7 during cervical decompression that aims to preserve cervicothoracic junction stability and potentially reduce pain. Cervical spondylotic myelopathy can result from degenerative cervical spinal disease including, herniated disk material, osteophytes, redundant ligamentum flavum, or ossification of the posterior longitudinal ligament. Surgical intervention for multilevel myelopathy aims to decompress the spinal cord and maintain stability of the cervical spine. Multilevel laminectomy is traditionally used when degenerative changes affect 3 or more levels and when there is primarily dorsal compressive disease. Traditional laminectomy can result in instability and kyphosis. The C7 lamina can be particularly vulnerable given the location at cervicothoracic junction. We describe an obtuse-angled laminotomy for the most caudal lamina in a planned decompression. This lamina is left attached to ligamentum nuchea, adjacent fascia, and paravertebral muscles. Only the base of spinous process and ventral portion of lamina's cortical and cancellous bone are removed in an obtuse angle through the opening. This variation is aimed to preserve as much of the cervical stability while still achieving the goal of decompression. PMID- 26889987 TI - How High Are Radiation-related Risks in Minimally Invasive Transforaminal Lumbar Interbody Fusion Compared With Traditional Open Surgery?: A Meta-analysis and Dose Estimates of Ionizing Radiation. AB - STUDY DESIGN: Meta-analysis and dose estimation. OBJECTIVE: The aim of this study was to estimate radiation dose during minimally invasive transforaminal lumbar interbody fusion (MiTLIF) compared with open transforaminal lumbar interbody fusion (OTLIF) and evaluate the risk of radiation-related disease. SUMMARY OF BACKGROUND DATA: MiTLIF was introduced to reduce soft tissue injury and shows favorable perioperative outcomes. However, the disadvantage of MiTLIF is that, compared with OTLIF, it involves high radiation exposure because MiTLIF usually depends on a fluoroscopic guide. The additional cancer risk due to medical radiation exposure during the MiTLIF procedure has not yet been assessed. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials in June 2014 for studies directly comparing MiTLIF and OTLIF. Patient demographics, fluoroscopy time, intraoperative bleeding, and hospitalization period were extracted. The effective dose was converted from fluoroscopy time using formulas from prior studies. RESULTS: Eight cohort studies with a total of 619 patients were identified. Mean fluoroscopy time was 39.42 seconds [95% confidence interval (CI), 38.01-40.83] during OTLIF and 94.21 seconds (95% CI, 91.51-96.91) during MiTLIF according to the meta-analysis. The pooled data revealed that patients who underwent MiTLIF were exposed to 2.4-fold more radiation than those who underwent OTLIF. Patients who underwent OTLIF and MiTLIF were exposed to 0.66 mSv (95% CI, 0.64-0.69) and 1.58 mSv (95% CI, 1.54 1.63) during the surgery, respectively. The lifetime risk of cancer was theoretically increased by 36.4*10 and 87.0*10 after OTLIF and MiTLIF, respectively. The risk of detrimental hereditary disorders associated with OTLIF and MiTLIF is 1.32*10 and 3.16*10, respectively. CONCLUSIONS: Patients who underwent MiTLIF were exposed to 2.4-fold more radiation than those who underwent OTLIF. Although the theoretical cancer risk associated with radiation exposure may be tolerable, stochastic effects should not be disregarded. PMID- 26889988 TI - Understanding Time-driven Activity-based Costing. AB - Transitioning to a value-based health care system will require providers to increasingly scrutinize their outcomes and costs. Although there has been a great deal of effort to understand outcomes, cost accounting in health care has been a greater challenge. Currently the cost accounting methods used by hospitals and providers are based off a fee-for-service system. As resources become increasingly scarce and the health care system attempts to understand which services provide the greatest value, it will be critically important to understand the true costs of delivering a service. An understanding of the true costs of a particular service will help providers make smarter decisions on how to allocate and utilize resources as well as determine which activities are nonvalue added. Achieving value will require providers to have a greater focus on accurate outcome data as well as better methods of cost accounting. PMID- 26889990 TI - Long-term Outcome After Monosegmental L4/5 Stabilization for Degenerative Spondylolisthesis With the Dynesys Device. AB - STUDY DESIGN: Retrospective analysis of prospectively collected clinical data. OBJECTIVE: To assess the long-term outcome of patients with monosegmental L4/5 degenerative spondylolisthesis treated with the dynamic Dynesys device. SUMMARY OF BACKGROUND DATA: The Dynesys system has been used as a semirigid, lumbar dorsal pedicular stabilization device since 1994. Good short-term results have been reported, but little is known about the long-term outcome after treatment for degenerative spondylolisthesis at the L4/5 level. METHODS: A total of 39 consecutive patients with symptomatic degenerative lumbar spondylolisthesis at the L4/5 level were treated with bilateral decompression and Dynesys instrumentation. At a mean follow-up of 7.2 years (range, 5.0-11.2 y), they underwent clinical and radiographic evaluation and quality of life assessment. RESULTS: At final follow-up, back pain improved in 89% and leg pain improved in 86% of patients compared with preoperative status. Eighty-three percent of patients reported global subjective improvement. Ninety-two percent would undergo the surgery again. Eight patients (21%) required further surgery because of symptomatic adjacent segment disease (6 cases), late-onset infection (1 case), and screw breakage (1 case). In 9 cases, radiologic progression of spondylolisthesis at the operated segment was found. Seventy-four percent of operated segments showed limited flexion-extension range of <4 degrees. Adjacent segment pathology, although without clinical correlation, was diagnosed at the L5/S1 (17.9%) and L3/4 (28.2%) segments. In 4 cases, asymptomatic screw loosening was observed. CONCLUSIONS: Monosegmental Dynesys instrumentation of degenerative spondylolisthesis at L4/5 shows good long-term results. The rate of secondary surgeries is comparable to other dorsal instrumentation devices. Residual range of motion in the stabilized segment is reduced, and the rate of radiologic and symptomatic adjacent segment degeneration is low. Patient satisfaction is high. Dynesys stabilization of symptomatic L4/5 degenerative spondylolisthesis is a possible alternative to other stabilization devices. PMID- 26889989 TI - Three-Dimensional Isotropic MRI of the Cervical Spine: A Diagnostic Comparison With Conventional MRI. AB - STUDY DESIGN: Retrospective diagnostic trial. OBJECTIVE: To determine the diagnostic performance of 3-dimensional turbo spin-echo (3D-TSE) isotropic magnetic resonance imaging (MRI) in the assessment of cervical spine pathology. SUMMARY OF BACKGROUND DATA: MRI is the imaging modality of choice for many cervical spine pathologies. However, axial imaging may be suboptimal if the image plane is oriented differently than the plane of interest, due to lordosis, kyphosis, or deformity. 3D-TSE isotropic MRI is a promising novel technology that bypasses this limitation by enabling dynamic image reformation in any desired orientation. METHODS: Forty-eight patients who underwent 3D-TSE and conventional 2-dimensional fast spin-echo (2D-FSE) T2-weighted cervical spine MRI at our institution were randomly selected. 3D-TSE and 2D-FSE sequences from each subject were independently evaluated by 2 orthopedic spine surgeons and 4 musculoskeletal radiologists. Images were assessed using specific pilot-tested criteria for stenosis, herniation, and degenerative changes. Intermethod, interrater, and intrarater agreements for 3D-TSE and 2D-FSE, and Fleiss kappa coefficients were determined. RESULTS: The overall intermethod agreement was 80.7%. The interrater agreement was 75.9% for 3D-TSE and 75.7% for 2D-FSE (P=0.47). The intrarater agreement was 82.2% for 3D-TSE and 81.5% for 2D-FSE (P=0.71). Fleiss kappa coefficients were 0.42 for 3D-TSE and 0.43 for 2D-FSE (P=0.62), indicating moderate interrater reliability. The intermethod agreement and the 2D-FSE intrarater agreement were statistically similar (P=0.49). CONCLUSIONS: There is a high degree of agreement between 3D-TSE and 2D-FSE MRI in assessing the cervical spine. The intermethod variability was statistically similar to the intrinsic intrarater variability of 2D-FSE MRI. This study demonstrates that 3D-TSE yields at least equivalent diagnostic information as conventional 2D-FSE in the cervical spine. In addition, reviewers noted subjective advantages of 3D-TSE image reprocessing, especially when evaluating greater pathology or deformity, with a simplified image acquisition process. PMID- 26889991 TI - The Biomechanical Properties of Pedicle Screw Fixation Combined With Trajectory Bone Cement Augmentation in Osteoporotic Vertebrae. AB - STUDY DESIGN: The biomechanics of pedicle screw fixation combined with trajectory cement augmentation with various filling volumes were measured by pull-out, periodic antibending, and compression fatigue tests. OBJECTIVE: To investigate the biomechanical properties of the pedicle screw fixation combined with trajectory bone cement (polymethylmethacrylate) augmentation in osteoporotic vertebrae and to explore the optimum filling volume of the bone cement. SUMMARY OF BACKGROUND DATA: Pedicle screw fixation is considered to be the most effective posterior fixation method. The decrease of the bone mineral density apparently increases the fixation failure risk caused by screw loosening and displacement. Trajectory bone cement augmentation has been confirmed to be an effective method to increase the bone intensity and could markedly increase the stability of the fixation interface. METHODS: Sixteen elderly cadaveric 1-5 lumbar vertebral specimens were diagnosed with osteoporosis. The left and right vertebral pedicles were alternatively randomized for treatment in all groups, with the contralateral pedicles as control. The study groups included: group A (pedicle screw fixation with full trajectory bone cement augmentation), group B (75% filling), group C (50% filling), and group D (25% filling). Finally, the bone cement leakage and dispersion were assessed and the mechanical testing was conducted. RESULTS: The bone cement was well dispersed around the pedicle screw. The augmented bone intensity, pull-out strength, periodic loading times, and compression fatigue performance were markedly higher than those of the control groups. With the increase in trajectory bone cement, the leakage was also increased (P<0.05). The pull-out strength of the pedicle screw was increased with an increase in bone mineral density and trajectory bone cement. It peaked at 75% filling, with the largest power consumption. CONCLUSIONS: The optimal filling volume of the bone cement was 75% of the trajectory volume (about 1.03 mL). The use of excessive bone cement did not increase the fixation intensity but increased the risk of leakage. PMID- 26889992 TI - Bipolar Sealer Device Reduces Blood Loss and Transfusion Requirements in Posterior Spinal Fusion for Degenerative Lumbar Scoliosis: A Randomized Control Trial. AB - STUDY DESIGN: A prospective, randomized, controlled clinical study. OBJECTIVE: To determine the efficacy of bipolar sealer device in reducing perioperative blood loss and transfusions in degenerative lumbar scoliosis patients undergoing primary posterior spinal fusion. BACKGROUND: It has recently been used successfully in pediatric spine surgery, particularly in idiopathic and neuromuscular deformities. However, there is a dearth of literature on prospective study of the efficacy of bipolar sealer device in reducing perioperative blood loss and transfusions in patients undergoing degenerative lumbar scoliosis surgery. METHODS: A total of 100 consecutive degenerative lumbar scoliosis patients who had undergone primary decompression and posterior spinal fusion with segmental spinal instrumentation between June 2010 and June 2012 were prospectively randomized into 1 of 2 groups according to whether bipolar sealer device for intraoperative/postoperative blood management was used or not. Demographic distribution, perioperative blood loss, blood transfusion rate, the length of stay, and postoperative complications were analyzed. RESULTS: The operation time was significantly shorter in the study group than in the control group, 223.4 versus 248.9 minutes (P=0.026). There was significantly lower intraoperative estimated blood loss in the bipolar sealer group, 407 versus 696 mL (P=0.000). Of the patients with the use of bipolar sealer device, the mean red blood cell transfusion requirement during hospitalization was significantly less than the control group, 0.4 versus 1.1 U/patient (P=0.003). Furthermore, significant difference existed in allogenic blood transfusion rate between the 2 cohorts. Within the study group (with the use of bipolar sealer device), the entire perioperative allogenic blood transfusion rate was 18.0% compared with 40.0% of the control group (P=0.015). There were no complications related directly to the use of the bipolar sealer. CONCLUSIONS: Utilization of a bipolar sealer during correction of lumbar degenerative scoliosis may offer comparable hemostatic effects, without prohibitive cost or adverse drug-related risks. PMID- 26889993 TI - A Comparison of Zero-Profile Devices and Artificial Cervical Disks in Patients With 2 Noncontiguous Levels of Cervical Spondylosis. AB - STUDY DESIGN: A prospective randomized and controlled study of 30 patients with 2 noncontiguous levels of cervical spondylosis. OBJECTIVE: To compare the clinical outcome between zero-profile devices and artificial cervical disks for noncontiguous cervical spondylosis. SUMMARY OF BACKGROUND DATA: Noncontiguous cervical spondylosis is an especial degenerative disease of the cervical spine. Some controversy exists over the choice of surgical procedure and fusion levels for it because of the viewpoint that the stress at levels adjacent to a fusion mass will increase. The increased stress will lead to the adjacent segment degeneration (ASD). According to the viewpoint, the intermediate segment will bear more stress after both superior and inferior segments' fusion. Cervical disk arthroplasty is an alternative to fusion because of its motion-preserving. Few comparative studies have been conducted on arthrodesis with zero-prolife devices and arthroplasty with artificial cervical disks for noncontiguous cervical spondylosis. METHODS: Thirty patients with 2 noncontiguous levels of cervical spondylosis were enrolled and assigned to either group A (receiving arthroplasty using artificial cervical disks) and group Z (receiving arthrodesis using zero profile devices). The clinical outcomes were assessed by the mean operative time, blood loss, Japanese Orthopedic Association (JOA) score, Neck Dysfunction Index (NDI), cervical lordosis, fusion rate, and complications. RESULTS: The mean follow-up was 32.4 months. There were no significant differences between the 2 groups in the blood loss, JOA score, NDI score, and cervical lordosis except operative time. The mean operative time of group A was shorter than that of group Z. Both the 2 groups demonstrated a significant increase in JOA score, NDI score, and cervical lordosis. The fusion rate was 100% at 12 months postoperatively in group Z. There was no significant difference between the 2 groups in complications except the ASD. Three patients had radiologic ASD at the final follow-up in group Z, and none in group A. CONCLUSIONS: Both zero-prolife devices and artificial cervical disks are generally effective and safe in the treatment of 2 noncontiguous levels of cervical spondylosis. However, in view of occurrence of the radiologic ASD and operative time, we prefer to artificial cervical disks if indications are well controlled. PMID- 26889994 TI - Cost-Utility Analysis of Anterior Cervical Discectomy and Fusion With Plating (ACDFP) Versus Posterior Cervical Foraminotomy (PCF) for Patients With Single level Cervical Radiculopathy at 1-Year Follow-up. AB - STUDY DESIGN: A retrospective 1-year cost-utility analysis. OBJECTIVE: To determine the cost-effectiveness of anterior cervical discectomy and fusion with plating (ACDFP) in comparison with posterior cervical foraminotomy (PCF) for patients with single-level cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical radiculopathy due to cervical spondylosis is commonly treated by either PCF or ACDFP for patients who are refractory to nonsurgical treatment. Although some have suggested superior outcomes with ACDFP as compared with PCF, the former is also associated with greater costs. The present study analyzes the cost effectiveness of ACDFP versus PCF for patients with single-level cervical radiculopathy. METHODS: Forty-five patients who underwent ACDFP and 25 patients who underwent PCF for single-level cervical radiculopathy were analyzed. One-year postoperative health outcomes were assessed based on Visual Analogue Scale, Pain Disability Questionnaire, Patient Health Questionnaire, and EuroQOL-5 Dimensions questionnaires to analyze the comparative effectiveness of each procedure. Direct medical costs were estimated using Medicare national payment amounts and indirect costs were based on patient missed work days and patient income. Postoperative 1 year cost/utility ratios and the incremental cost-effectiveness ratio (ICER) were calculated to assess for cost-effectiveness using a threshold of $100,000/QALY gained. RESULTS: The 1-year cost-utility ratio for the PCF cohort was significantly lower ($79,856/QALY gained) than that for the ACDFP cohort ($131,951/QALY gained) (P<0.01). In calculating the 1-year ICER, as the ACDFP cohort showed lower QALY gained than the PCF cohort, the ICER was negative and is not reported, meaning that ACDFP was dominated by PCF. CONCLUSIONS: Statistically significant and clinically relevant improvements (through minimum clinically important differences) were seen in both cohorts. Although both cohorts showed improved health outcomes, ACDFP was not cost-effective relative to the threshold of $100,000/QALY gained at 1-year postoperatively, whereas PCF was. The durability of these results must be analyzed with long-term cost-utility analysis studies. PMID- 26889995 TI - Early Clinical Outcomes and Radiographic Features After Treatment of Cervical Degenerative Disk Disease With the New Zero-Profile Implant: A 1-Year Follow-up Retrospective Study. AB - STUDY DESIGN: Retrospective study of 52 patients who underwent anterior cervical fusion with the new implant. OBJECTIVE: To investigate the clinical outcomes and complications of the new implant for anterior cervical discectomy and fusion, and evaluate the radiographic features in the treatment of cervical degenerative diseases. SUMMARY OF BACKGROUND DATA: Although high fusion rates can be achieved with the anterior cervical plate, plate-related morbidity affects the patient's satisfaction with the surgical outcomes. METHODS: A retrospective study was performed in 52 consecutive patients who used the new implant at 106 levels. The clinical outcomes were evaluated preoperatively and postoperatively using the visual analog scale score for neck and arm pain and the Japanese Orthopedic Association and ASIA motor score for myelopathy preoperatively and postoperatively. The cervical curvature, the segment height, and fusion status were assessed on radiographs during a mean 12-month follow-up period. RESULTS: There was statistically significant difference in perioperative neck and arm visual analog scale pain score. The preoperative Japanese Orthopedic Association and ASIA motor scores were significantly lower than those before surgery (P<0.05), and this difference was maintained at the last follow-up. The occurrence of dysphagia was 11.5%, which was significantly lower than that reported in the previous literature. There was significant difference in lordosis before and after surgery (10.9+/-12.2 vs. 23.7+/-11.3, P<0.01) in the trisegmental group. The anterior disk height and interbody height of targeting segments increased from preoperative 5.1+/-1.56 and 31.9+/-3.43 to postoperative 9.1+/-1.02 and 36.7+/-2.44, respectively. Firm fusion was observed in all patients. CONCLUSIONS: Our investigations suggest that this new implant facilitates anterior cervical surgery with satisfactory clinical outcomes and a low rate of dysphagia. Our study has demonstrated that this new implant is able to restore and maintain physiological lordosis and segment height of the cervical spine postoperatively. PMID- 26889996 TI - Cost-Utility Analysis of Instrumented Fusion Versus Decompression Alone for Grade I L4-L5 Spondylolisthesis at 1-Year Follow-up: A Pilot Study. AB - STUDY DESIGN: Retrospective 1-year cost-utility analysis. OBJECTIVE: To determine the cost-effectiveness of decompression with and without instrumented fusion for patients with grade I degenerative L4-L5 spondylolisthesis at 1-year follow-up. SUMMARY OF BACKGROUND DATA: Despite its benefits to health outcomes, lumbar fusion is associated with substantial costs. This study analyzed the cost effectiveness of instrumented fusion for grade I L4-L5 spondylolisthesis at 1 year follow-up. MATERIALS AND METHODS: Four cohorts of 25 patients with grade I L4-L5 degenerative spondylolisthesis were analyzed: cohort 1 (decompression), cohort 2 (decompression with instrumented posterolateral fusion (PLF), cohort 3 (decompression with instrumented posterior lumbar interbody fusion/transforaminal lumbar interbody fusion), and cohort 4 (decompression with instrumented PLF and posterior lumbar interbody fusion/transforaminal lumbar interbody fusion). One year postoperative health outcomes were assessed based on Visual Analogue Scale, Pain Disability Questionnaire, and EuroQol 5 Dimensions questionnaires. Direct medical costs were estimated using Medicare national payment amounts and indirect costs were based on patient missed work days. Postoperative 1-year cost/utility ratios and incremental cost-effectiveness ratios (ICERs) were calculated. Cost effectiveness was assessed using a threshold of $100,000/QALY gained. RESULTS: Compared with preoperative health states, EuroQol 5 Dimensions QALY scores improved for all cohorts (P<0.01). The 1-year cost-utility ratio for cohort 1 was significantly lower ($56,610/QALY gained; P<0.01) than that for cohorts 2 ($116,991/QALY gained), 3 ($109,740/QALY gained), and 4 ($107,546/QALY gained). The 1-year ICERs relative to cohort 1 were: cohort 2 (dominated), cohort 3 ($1,060,549/QALY gained), and cohort 4 ($830,047/QALY gained). CONCLUSIONS: Decompression without fusion is cost-effective for patients with grade I L4-L5 spondylolisthesis. Decompression with fusion is not cost effective in a 1-year timeframe for these patients based on the threshold. Accordingly, although fusion is beneficial for improving health outcomes in patients with spondylolisthesis, it is not cost-effective when analyzing a 1-year timeframe based on the threshold. The durability of these results must be analyzed with longer term cost utility analysis studies. PMID- 26889997 TI - Radiographic Restoration of Sagittal Spinopelvic Alignment After Posterior Lumbar Interbody Fusion in Degenerative Spondylolisthesis. AB - STUDY DESIGN: A retrospective study. OBJECTIVES: This study was aimed to analyze the changes in spinopelvic parameters after surgical correction of degenerative spondylolisthesis and to determine which deformity is most responsible for changes in sagittal spinopelvic alignment. SUMMARY OF BACKGROUND DATA: The basic deformities of degenerative spondylolisthesis are forward slippage of the vertebral body, segmental kyphotic angle, and loss of disk height. Correction of those deformities during surgery will subsequently affect the spinopelvic parameters. A few studies have reported the changes of sagittal spinopelvic alignment after surgical treatment of isthmic spondylolisthesis. However, there appears to be relatively little information regarding degenerative spondylolisthesis. MATERIALS AND METHODS: Fifty-three patients with L4-L5 degenerative spondylolisthesis were included. All patients underwent posterior lumbar interbody fusion and posterior instrumentation. Back pain, as the clinical outcome, was evaluated by visual analogue scale (VAS). The preoperative and postoperative spinopelvic parameters, including sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), and L1 axis S1 distance were measured, and then the correlations between spinopelvic parameters and local deformity parameters such as slip degree, slip angle (SA), and height of the intervertebral disk were evaluated. RESULTS: After surgical correction of local deformity, all spinopelvic parameters changed subsequently: PT and L1 axis S1 distance had a decrease, SS and LL had an increase. VAS score decreased from 6.1+/-2.3 before surgery to 2.4+/-1.7 at the final follow-up assessment. Patients with VAS score changes >=3 showed significantly higher SS and LL, and lower PT compared with those with VAS score changes <3. Among deformity parameters, restoration of the SA revealed significant correlation with improvement of LL (r=0.32, P=0.02), increase of SS (r=0.29, P=0.03), and decrease of PT (r=-0.29, P=0.03). CONCLUSIONS: Surgical correction of degenerative spondylolisthesis with posterior lumbar interbody fusion and posterior instrumentation resulted in relief of back pain, which may be associated with improvement of sagittal spinopelvic alignment. Surgeons should consider deformity parameters, especially the SA, in the surgical treatment of degenerative spondylolisthesis. PMID- 26889999 TI - Indications and Techniques for Spinal Instrumentation in Thoracic Disk Surgery. AB - STUDY DESIGN: Retrospective case series. OBJECTIVE: To identify the indications, techniques, and outcomes for instrumented fusion during thoracic discectomy. SUMMARY OF BACKGROUND DATA: Thoracic discectomy may require extensive bone removal to avoid spinal cord manipulation, but the indications and techniques for instrumented fusion during thoracic discectomy remain poorly delineated. METHODS: The authors identified 220 consecutive patients who underwent thoracic discectomy between 1992 and 2012. Clinical and radiographic variables were compared between patients who underwent instrumented fusion and patients without instrumentation, and among surgical approaches utilized for discectomy. RESULTS: Patient age for the entire cohort averaged 49+/-13.01 years, and mean clinical follow-up was 45 months (range, 1-218 mo). Patients underwent 226 thoracic discectomy procedures, including 48 thoracotomy, 136 thoracoscopy, and 42 posterolateral approaches. Seventy-eight patients required instrumented fusion and, compared with patients without instrumentation, were more likely to present with myelopathy (P<0.0001) and harbor giant (P=0.0012), calcified (P=0.019), or transdural (P=0.0004) herniated disks. Surgery with instrumentation resulted in greater blood loss (P<0.0001), longer hospital stay (P<0.0001), and a higher complication rate (22% vs. 9.9%), yet patients in both cohorts had similar rates of symptom resolution postoperatively. Of the patients who underwent thoracic discectomy without instrumentation, 3 (2.1%) developed delayed deformity or instability and required subsequent surgery for fixation and fusion at an average 6.3 months postoperatively (range, 4-8 mo). Patients who underwent instrumented fusion exhibited no nonunions or delayed deformity. CONCLUSIONS: Thoracic discectomy without fixation is a reasonable clinical option in carefully selected patients, but instrumented fusion is safe and effective in other patients. Indications for fixation and fusion are thus proposed. PMID- 26889998 TI - Increased Preoperative Narcotic Use and Its Association With Postoperative Complications and Length of Hospital Stay in Patients Undergoing Spine Surgery. AB - STUDY DESIGN: Prospective cohort analysis. OBJECTIVE: To assess the effect of preoperative narcotic use on the incidence of 30- and 90-day postoperative complications, as well as length of hospital stay (LOS) in patients undergoing spine surgery. SUMMARY OF BACKGROUND DATA: Previous work has associated an increased incidence of complications and length of stay following surgery in patients with increased preoperative narcotic use. Despite this and recent national attention highlighting the negative effects of narcotics, they remain commonly used for the management of pain in patients undergoing spine surgery. MATERIALS AND METHODS: A total of 583 patients undergoing spine surgery for a structural lesion were evaluated. Self-reported preoperative narcotic consumption was obtained and converted to morphine equivalents at the initial preoperative visit. LOS was recorded upon discharge and presence/type of a postoperative complication within 30/90 days was obtained. A multivariable logistic and linear regression analysis was performed for the incidence of complications and length of stay controlling for clinically important covariates. RESULTS: Narcotic use was not associated with 30- or 90-day complications; however, smoking status was significantly associated with 30-day complications. Increased preoperative narcotic use was significantly associated with increased LOS, as was age, type of surgery, and depression. CONCLUSIONS: Increased preoperative narcotic use and depression are associated with increased LOS in patients undergoing spine surgery. We calculated that for every 100 morphine equivalents a patient is taking preoperatively; their stay is extended 1.1 days. Narcotic use was not associated with 30- or 90-day postoperative complications. As reimbursement is bundled before surgery, providing interventions for patients with treatable causes for increased length of stay can save cost overall. PMID- 26890001 TI - Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities. AB - BACKGROUND: We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. METHODS: A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). FINDINGS: For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. INTERPRETATION: In the absence of an expanded NEP in CJ, the combined interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component. PMID- 26890000 TI - Copper Nanoparticles and Copper Sulphate Induced Cytotoxicity in Hepatocyte Primary Cultures of Epinephelus coioides. AB - Copper nanoparticles (Cu-NPs) were widely used in various industrial and commercial applications. The aim of this study was to analyze the cytotoxicity of Cu-NPs on primary hepatocytes of E.coioides compared with copper sulphate (CuSO4). Cultured cells were exposed to 0 or 2.4 mg Cu L-1 as CuSO4or Cu-NPs for 24-h. Results showed either form of Cu caused a dramatic loss in cell viability, more so in the CuSO4 than Cu-NPs treatment. Compared to control, either CuSO4 or Cu-NPs significantly increased reactive oxygen species(ROS) and malondialdehyde(MDA) concentration in hepatocytes by overwhelming total superoxide dismutase (T-SOD) activity, catalase(CAT) activity and glutathione(GSH) concentration. In addition, the antioxidative-related genes [SOD (Cu/Zn), SOD (Mn), CAT, GPx4] were also down-regulated. The apoptosis and necrosis percentage was significantly higher after the CuSO4 or Cu-NPs treatment than the control. The apoptosis was induced by the increased cytochrome c concentration in the cytosol and elevated caspase-3, caspase-8 and caspase-9 activities. Additionally, the apoptosis-related genes (p53, p38beta and TNF alpha) and protein (p53 protein) were up-regulated after the CuSO4 or Cu-NPs treatment, with CuSO4 exposure having a greater effect than Cu-NPs. In conclusion, Cu-NPs had similar types of toxic effects as CuSO4 on primary hepatocytes of E.coioides, but toxicity of CuSO4 was more severe than that of Cu NPs. PMID- 26890002 TI - Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification. AB - Vascular calcification is an important risk factor associated with mortality among patients with chronic kidney disease. Intracellular cholesterol metabolism is involved in the process of vascular cell calcification. In this study, we investigated the role of UbiA prenyltransferase domain containing 1 (UBIAD1) in intracellular cholesterol metabolism and vascular cell calcification, and identified its subcellular location. Primary human umbilical vein smooth muscle cells (HUVSMCs) were incubated with either growth medium (1.4 mmol/L Pi) or calcification medium (CM) (3.0 mmol/L Pi). Under treatment with CM, HUVSMCs were further incubated with exogenous cholesterol, or menaquinone-4, a product of UBIAD1. The plasmid and small interfering RNA were transfected in HUVSMCs to alter the expression of UBIAD1. Matrix calcium quantitation, alkaline phosphatase activity, intracellular cholesterol level and menaquinone-4 level were measured. The expression of several genes involved in cholesterol metabolism were analyzed. Using an anti-UBIAD1 antibody, an endoplasmic reticulum marker and a Golgi marker, the subcellular location of UBIAD1 in HUVSMCs was analyzed. CM increased matrix calcium, alkaline phosphatase activity and intracellular cholesterol level, and reduced UBIAD1 expression and menaquinone-4 level. Addition of cholesterol contributed to increased matrix calcification and alkaline phosphatase activity in a dose-dependent manner. Elevated expression of UBIAD1 or menaquinone-4 in HUVSMCs treated with CM significantly reduced intracellular cholesterol level, matrix calcification and alkaline phosphatase activity, but increased menaquinone-4 level. Elevated expression of UBIAD1 or menaquinone-4 reduced the gene expression of sterol regulatory element-binding protein-2, and increased gene expression of ATP binding cassette transporters A1, which are in charge of cholesterol synthesis and efflux. UBIAD1 co-localized with the endoplasmic reticulum marker and the Golgi marker in HUVSMCs. In conclusion, high intracellular cholesterol content contributes to phosphate-induced vascular cell differentiation and calcification. UBIAD1 or menaquinone-4 could decrease vascular cell differentiation and calcification, probably via its potent role of inversely modulating cellular cholesterol. PMID- 26890003 TI - The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia. AB - Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU->HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU->HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression. PMID- 26890005 TI - A comprehensive review of the epidemiology and disease burden of Influenza B in 9 European countries. AB - This review was undertaken to consolidate information on the epidemiology and burden of influenza B, as well as the circulation patterns of influenza B lineage in 9 European countries. Following a comprehensive search of peer-reviewed and gray literature sources, we found that published data on influenza B epidemiology and burden are scarce. Surveillance data show frequent co-circulation of both influenza B lineages during influenza seasons, but little is known about its impact, especially in adults and the clinical burden of influenza B remains unknown. Mismatch between the circulating influenza B lineage and vaccine recommendations has been seen in at least one influenza season in every country. Such observations could impact the effectiveness of seasonal influenza vaccination programs using trivalent vaccines, which contain only one influenza B lineage (B/Yamagata or B/Victoria) and highlight the need for local studies to better understand the epidemiology and burden of influenza B in these countries. PMID- 26890007 TI - State-of-the-Art Treatment and Novel Agents in Chronic Lymphocytic Leukemia. AB - Chemoimmunotherapy is the established first-line treatment of patients with chronic lymphocytic leukemia (CLL) who do not display the high-risk genetic features del(17p) and/or TP53 mutation: Physically fit patients without or with only mild comorbidities should receive fludarabine, cyclophosphamide and rituximab, while bendamustine and rituximab can be considered in fit elderly patients of over 65 years and in patients with a higher risk of infections. Patients with relevant coexisting conditions should receive chlorambucil with a CD20 antibody, preferably obinutuzumab. Patients with a del(17p) and/or TP53 mutation respond poorly to conventional chemo(immuno)therapies. However, the recently approved BTK and PI3K inhibitors ibrutinib and idelalisib have the best efficacy ever documented in patients with these high-risk genomic alterations and/or refractory CLL. The choice between ibrutinib and idelalisib should be based on the patients' comorbidities and concomitant medications since both agents have a distinct toxicity profile, although they are generally well tolerated in the majority of patients. For treatment of patients with a late relapse, chemoimmunotherapy instead of kinase inhibitors is still a reasonable approach, but has to be determined for every patient individually. Further targeted drugs and their combinations are currently being evaluated in clinical trials and have the potential to eradicate all residual CLL cells and thus lead to a cure of CLL. PMID- 26890006 TI - Clinical Nomograms to Predict Stone-Free Rates after Shock-Wave Lithotripsy: Development and Internal-Validation. AB - PURPOSE: Shock-wave lithotripsy (SWL) is accepted as the first line treatment modality for uncomplicated upper urinary tract stones; however, validated prediction models with regards to stone-free rates (SFRs) are still needed. We aimed to develop nomograms predicting SFRs after the first and within the third session of SWL. Computed tomography (CT) information was also modeled for constructing nomograms. MATERIALS AND METHODS: From March 2006 to December 2013, 3028 patients were treated with SWL for ureter and renal stones at our three tertiary institutions. Four cohorts were constructed: Total-development, Total validation, CT-development, and CT-validation cohorts. The nomograms were developed using multivariate logistic regression models with selected significant variables in a univariate logistic regression model. A C-index was used to assess the discrimination accuracy of nomograms and calibration plots were used to analyze the consistency of prediction. RESULTS: The SFR, after the first and within the third session, was 48.3% and 68.8%, respectively. Significant variables were sex, stone location, stone number, and maximal stone diameter in the Total-development cohort, and mean Hounsfield unit (HU) and grade of hydronephrosis (HN) were additional parameters in the CT-development cohort. The C-indices were 0.712 and 0.723 for after the first and within the third session of SWL in the Total-development cohort, and 0.755 and 0.756, in the CT development cohort, respectively. The calibration plots showed good correspondences. CONCLUSIONS: We constructed and validated nomograms to predict SFR after SWL. To the best of our knowledge, these are the first graphical nomograms to be modeled with CT information. These may be useful for patient counseling and treatment decision-making. PMID- 26890004 TI - Gbeta Regulates Coupling between Actin Oscillators for Cell Polarity and Directional Migration. AB - For directional movement, eukaryotic cells depend on the proper organization of their actin cytoskeleton. This engine of motility is made up of highly dynamic nonequilibrium actin structures such as flashes, oscillations, and traveling waves. In Dictyostelium, oscillatory actin foci interact with signals such as Ras and phosphatidylinositol 3,4,5-trisphosphate (PIP3) to form protrusions. However, how signaling cues tame actin dynamics to produce a pseudopod and guide cellular motility is a critical open question in eukaryotic chemotaxis. Here, we demonstrate that the strength of coupling between individual actin oscillators controls cell polarization and directional movement. We implement an inducible sequestration system to inactivate the heterotrimeric G protein subunit Gbeta and find that this acute perturbation triggers persistent, high-amplitude cortical oscillations of F-actin. Actin oscillators that are normally weakly coupled to one another in wild-type cells become strongly synchronized following acute inactivation of Gbeta. This global coupling impairs sensing of internal cues during spontaneous polarization and sensing of external cues during directional motility. A simple mathematical model of coupled actin oscillators reveals the importance of appropriate coupling strength for chemotaxis: moderate coupling can increase sensitivity to noisy inputs. Taken together, our data suggest that Gbeta regulates the strength of coupling between actin oscillators for efficient polarity and directional migration. As these observations are only possible following acute inhibition of Gbeta and are masked by slow compensation in genetic knockouts, our work also shows that acute loss-of-function approaches can complement and extend the reach of classical genetics in Dictyostelium and likely other systems as well. PMID- 26890008 TI - Exciton and charge carrier dynamics in few-layer WS2. AB - Semiconducting transition metal dichalcogenides (TMDs) have been applied as the active layer in photodetectors and solar cells, displaying substantial charge photogeneration yields. However, their large exciton binding energy, which increases with decreasing thickness (number of layers), as well as the strong resonance peaks in the absorption spectra suggest that excitons are the primary photoexcited states. Detailed time-domain studies of the photoexcitation dynamics in TMDs exist mostly for MoS2. Here, we use femtosecond optical spectroscopy to study the exciton and charge dynamics following impulsive photoexcitation in few layer WS2. We confirm excitons as the primary photoexcitation species and find that they dissociate into charge pairs with a time constant of about 1.3 ps. The better separation of the spectral features compared to MoS2 allows us to resolve a previously undetected process: these charges diffuse through the samples and get trapped at defects, such as flake edges or grain boundaries, causing an appreciable change of their transient absorption spectra. This finding opens the way to further studies of traps in TMD samples with different defect contents. PMID- 26890009 TI - A relapsed aggressive NK-cell leukemia with CNS involvement diagnosed by cerebrospinal fluid examination. PMID- 26890010 TI - Oxygen-binding Protein Fiber and Microgel: Supramolecular Myoglobin Poly(acrylate) Conjugates. AB - A supramolecular conjugate of myoglobin (Mb) and water-soluble poly(acrylate), (PA5k and PA25k , where 5k and 25k represent the molecular weight of the polymers, respectively), is constructed on the basis of a noncovalent heme-heme pocket interaction. The modified heme with an amino group linked to the terminus of one of the heme-propionates is coupled to the side-chain carboxyl groups of poly(acrylate) activated by N-hydroxysuccinimide. The ratios of the heme-modified monomer unit and the unmodified monomer unit (m:n) in the polymer chains of Heme PA5k and Heme-PA25k were determined to be 4.5:95.5 and 3.1:96.9, respectively. Subsequent addition of apoMb to the conjugated polymers provides Mb-connected fibrous nanostructures confirmed by atomic force microscopy. A mixture of the heme-modified polymer and dimeric apomyoglobin as a cross-linker forms a microgel in which the reconstituted myoglobin retains its native exogenous ligand binding activity. PMID- 26890011 TI - Correlation of clinical and biochemical hyperandrogenism in Thai women with polycystic ovary syndrome. AB - AIM: The aim of this study was to determine the correlation of clinical hyperandrogenism and biochemical hyperandrogenism (hyperandrogenemia) in Thai women with polycystic ovary syndrome (PCOS). METHODS: This cross-sectional study was conducted at Siriraj Hospital, Thailand. Subjects were 145 women with PCOS who were diagnosed in accordance with the revised Rotterdam 2003 criteria and registered during January to July 2008. Clinical hyperandrogenism was assessed using the modified Ferriman-Gallwey score for hirsutism, the American Academy of Dermatology criteria for severity of acne, and the Ludwig scale for androgenic alopecia and virilization. Biochemical hyperandrogenism was determined from serum concentration of total testosterone (TT), dehydroepiandrosterone sulfate and free testosterone (FT). RESULTS: The participants had a mean age of 25.5 +/- 6.5 years and a body mass index of 26.2 +/- 6.9 kg/m(2) . The most common presenting symptom was oligomenorrhea or amenorrhea. The most common expression of clinical hyperandrogenism was acne (56.6%). Most of the participants (84.8%) had high serum-FT. There was a statistically significant correlation between clinical and biochemical hyperandrogenism in the following pairs: hirsutism and FT (r = 0.3, P < 0.001); hirsutism and TT (r = 0.26, P < 0.001); and acne and TT (r = 0.26, P = 0.002). The others had little or no correlations. CONCLUSION: Clinical hyperandrogenism is not a good predictor for biochemical hyperandrogenism in Thai women with PCOS. A modified Ferriman-Gallwey score cut-off point of 8 has low sensitivity but high specificity for hyperandrogenemia; therefore, it is useful for the diagnosis but not useful for the exclusion of hyperandrogenemia in Thai women with PCOS. PMID- 26890013 TI - Aggregation-Induced Emission Active Probe for Light-Up Detection of Anionic Surfactants and Wash-Free Bacterial Imaging. AB - Anionic surfactants are widely used in daily life and industries, but their residues can cause serious damage to the environment. The current detection methods for anionic surfactants suffer from various limitations and a new detection strategy is highly desirable. Based on 2-(2-hydroxyphenyl)benzothiazole fluorogen with aggregation-induced emission characteristics, we have developed a fluorescent probe HBT-C18 for selective and sensitive detection of anionic surfactants. By in situ formation of catanionic aggregates or micelles with anionic surfactants, the emission intensity of the HBT-C18 probe can increase with increasing keto/enol emission ratio through restriction of intramolecular motion and excited-state intramolecular proton-transfer mechanisms. The probe can also be used for wash-free imaging of bacteria enveloped by a negatively charged outer membrane. The results of this study provide a new strategy for sensitive detection of anionic surfactants and wash-free bacterial imaging. PMID- 26890014 TI - Subcutaneous Stimulation as ADD-ON Therapy to Spinal Cord Stimulation Is Effective in Treating Low Back Pain in Patients With Failed Back Surgery Syndrome: A Multicenter Randomized Controlled Trial. AB - OBJECTIVE: Suppression of back pain with traditional spinal cord stimulation (SCS) in failed back surgery syndrome patients is often insufficient. The objective of this study was to investigate the efficacy of subcutaneous stimulation (SubQ) as ADD-ON therapy to SCS in treating back pain in failed back surgery syndrome patients. MATERIALS AND METHODS: Patients with a minimal pain score of 50 on a 100 mm visual analog scale for both leg and back pain were eligible. If pain reduction after trial SCS was >=50% for the leg but <50% for the back, patients received additional SubQ leads and were randomized in a 1:1 ratio in a study arm with subcutaneous leads switched on (SubQ ADD-ON) and an arm with subcutaneous leads switched off (Control). The primary outcome was the percentage of the patients, at three months since implantation, with >=50% reduction of back pain. RESULTS: A total of 97 patients were treated with SCS for leg and back pain. Of these, 52 patients were randomized and allocated to the Control group (n = 24) or to the SubQ ADD-ON group (n = 28). The percentage of patients with >=50% reduction of back pain was significantly higher in the SubQ ADD-ON group (42.9%) compared to the Control group (4.2%). Mean visual analog scale for back pain, at three months, was a statistically significant 28.1 mm lower in the SubQ ADD-ON group compared to the Control group. CONCLUSION: Subcutaneous stimulation as an ADD-ON therapy to SCS is effective in treating back pain in failed back surgery syndrome patients where SCS is only effective for pain in the leg. PMID- 26890012 TI - Acceptability and Feasibility of Human Papilloma Virus Self-Sampling for Cervical Cancer Screening. AB - OBJECTIVES: Women in safety-net institutions are less likely to receive cervical cancer screening. Human papilloma virus (HPV) self-sampling is an alternative method of cervical cancer screening. We examine the acceptability and feasibility of HPV self-sampling among patients and clinic staff in two safety-net clinics in Miami. MATERIALS AND METHODS: Haitian and Latina women aged 30-65 years with no Pap smear in the past 3 years were recruited. Women were offered HPV self sampling or traditional Pap smear screening. The acceptability of HPV self sampling among patients and clinic staff was assessed. If traditional screening was preferred the medical record was reviewed. RESULTS: A total of 180 women were recruited (134 Latinas and 46 Haitian). HPV self-sampling was selected by 67% women. Among those selecting traditional screening, 22% were not screened 5 months postrecruitment. Over 80% of women agreed HPV self-sampling was faster, more private, easy to use, and would prefer to use again. Among clinic staff, 80% agreed they would be willing to incorporate HPV self-sampling into practice. CONCLUSIONS: HPV self-sampling was both acceptable and feasible to participants and clinic staff and may help overcome barriers to screening. PMID- 26890015 TI - Results From the Partnership for Advancement in Neuromodulation Registry: A 24 Month Follow-Up. AB - OBJECTIVE: This longitudinal, clinical outcome study was a multicenter, prospective, observational, registry with a 24-month assessment of patients implanted with spinal cord stimulation (SCS) systems for the management of chronic pain of the trunk and/or limbs. METHODS: On informed consent and institutional review board approval, 614 patients from 39 sites were enrolled within 30 days following permanent SCS system implantation. Medication usage, patient-reported pain relief (PRP), categorical ratings of pain relief, pain disability index scores (PDI), quality of life (QoL), and patient satisfaction were assessed at enrollment, 3-, 6-, 12-, 18-, and 24-month postimplant. Device related adverse events (AEs) were recorded and reported. RESULTS: Across all visits, statistically significant improvements were reported on all outcome measures. Mean PRP was 58.5% (+/- 26.4) at 3 months, 56.8% (+/- 29.2) at 6 months, 57.7% (+/- 28.9) at 12 months, 55.6% (+/- 29.8) at 18 months, and 56.3% (+/- 30.3) at 24 months. More than 65% of patients at any visit reported a PRP >= 50%. Mean PDI scores reduced from 46.9 points at baseline to 32.7, 31.8, 31.5, 32.1, 32.1 points at 3, 6, 12, 18, and 24 months (p <= 0.0001), respectively. Greater than 76% of patients at any visit were satisfied with their therapy. The majority of patients categorized pain relief as excellent or good on a 5-item scale and reported overall QoL as greatly improved or improved on a 5-item scale. An average of 88% of patients stopped, decreased, or did not change dose of narcotics/opioids. The most common AE was diminished or loss of pain relief in 11.4% of enrolled patients. CONCLUSIONS: Most patients experienced substantial pain relief and a significant improvement in all outcome measures. These results further support the safety, efficacy, and sustainability of SCS in clinical practice. PMID- 26890017 TI - Does Tonic Spinal Cord Stimulation Really Influence the Medial Pain System? PMID- 26890016 TI - Sensory Barrage Stimulation in the Treatment of Elbow Spasticity: A Crossover Double Blind Randomized Pilot Trial. AB - OBJECTIVE: To assess the feasibility of using a novel form of multichannel electrical stimulation, termed Sensory Barrage Stimulation (SBS) for the treatment of spasticity affecting the elbow flexor muscles and to compare this with conventional single-channel TENS stimulation. MATERIALS AND METHODS: Altogether ten participants with spasticity of the flexor muscles of the elbow of Grade 2 or above on the Modified Ashworth Scale (MAS) were recruited to this crossover double blind randomized trial. The participants received two intervention sessions (SBS and TENS), one week apart in a randomized order. Both interventions were applied over the triceps brachii on the affected arm for a duration of 60 minutes. Spasticity was measured using the MAS. Secondary outcome measures were self-reported change in spasticity, measured on a visual analog scale (VAS, 0-100), and therapist-rated strength of elbow extension and strength of elbow flexion. Measurements were taken immediately before each intervention was applied, immediately after the intervention, and one hour after the intervention. RESULTS: Immediately after stimulation spasticity showed a significant reduction for both TENS and SBS groups assessed by MAS -0.9 +/- 0.2 vs. -1.1 +/- 0.2 and by VAS -15 +/- 3 vs. -31 +/- 8. For SBS this improvement in MAS was still present at one hour after the stimulation, but not for TENS. Altogether seven SBS responders and four TENS responders were identified. CONCLUSIONS: This study demonstrates the feasibility and practicality of applying the new concept of SBS. Promising results indicate it causes a reduction in spasticity. PMID- 26890018 TI - Where motor disability and elite sports science meet. PMID- 26890019 TI - Advance care planning matters. PMID- 26890020 TI - Fatigue in childhood multiple sclerosis. PMID- 26890021 TI - Testing two screening instruments for autism spectrum disorder. PMID- 26890022 TI - Erratum. PMID- 26890023 TI - Erratum. PMID- 26890024 TI - Child restraint use and parental perceptions of comfort. AB - OBJECTIVE: Suboptimal child restraint use includes incorrect and/or inappropriate restraint use and increases the risk of injury. Comfort has been suggested as an important factor impacting on optimal use of restraints by children. This article aims to examine the relationships between parent reported comfort and restraint misuse and age-appropriate restraint choice. METHODS: This is an analysis of data from a cross sectional observation study of child restraint use in New South Wales. Logistic regression was used to model the relationship between parent reported comfort and restraint misuse and age-appropriate restraint choice. RESULTS: There was no significant relationship between either parent-reported comfort and restraint misuse or parent-reported comfort and age-appropriate restraint choice. CONCLUSIONS: Parent perceptions of comfort of children in child restraints do not appear to be associated with incorrect child restraint use or age appropriate restraint choice. It is possible that the actual comfort of the child may be related to incorrect use but this remains to be tested. Further investigation of the relationship between parent-perceived comfort and the actual comfort of the child, as well as the impact of child comfort on optimal child restraint use is warranted. PMID- 26890026 TI - Factors influencing the formation of polybromide monoanions in solutions of ionic liquid bromide salts. AB - Six different bromide salts - tetraethylammonium bromide ([N2,2,2,2]Br, Br), 1 ethyl-1-methylpiperidinium bromide ([C2MPip]Br, Br), 1-ethyl-1 methylpyrrolidinium bromide ([C2MPyrr]Br, Br), 1-ethyl-3-methylimidazolium bromide ([C2MIm]Br, Br), 1-ethylpyridinium bromide ([C2Py]Br, Br), and 1-(2 hydroxyethyl)pyridinium bromide ([C2OHPy]Br, Br) - were studied in regards to their capacity to form polybromide monoanion products on addition of molecular bromine in acetonitrile solutions. Using complementary spectroscopic and computational methods for the examination of tribromide and pentabromide anion formation, key factors influencing polybromide sequestration were identified. Here, we present criteria for the targeted synthesis of highly efficient bromine sequestration agents. PMID- 26890025 TI - 'Well, if the kids can do it, I can do it': older rehabilitation patients' experiences of telerehabilitation. AB - BACKGROUND AND OBJECTIVE: Although trials continue to emerge supporting the role of telerehabilitation, implementation has been slow. Key users include older people living with disabilities who are frequent users of hospital rehabilitation services but whose voices are rarely heard. It is unclear whether the use of technologies and reduced face-to-face contact is acceptable to these people. We report on a qualitative study of community dwelling participants who had received a home telerehabilitation programme as an alternative to conventional rehabilitation. DESIGN: Thirteen older participants, three spouses and one carer were interviewed. All had participated in an individualized therapy programme, using a combination of face-to-face and video consults with therapists. The programme used 'off-the-shelf' technologies including iPads for videoconferencing and electronic FitBitR devices. Interviews were recorded, transcribed verbatim and analysed using NVivo software. RESULTS: Thematic analysis resulted in five emergent themes: (i) telerehabilitation is convenient; (ii) telerehabilitation promotes motivation and self-awareness; (iii) telerehabilitation fosters positive therapeutic relationships; (iv) mastering technologies used by younger relatives is a valued aspect of telerehabilitation; and (v) Telerehabilitation does not replace traditional face-to-face rehabilitation therapies. CONCLUSIONS: Participants found telerehabilitation convenient and motivating, coped well with the technology and developed positive therapeutic relationships. The learning and practice aspects sat well in the context of a rehabilitation programme. The use of commercially available technologies may have contributed to respondents' high levels of acceptability. The perception of telerehabilitation as complementary to in-person care and the expectation of technological support have implications for the implementation and delivery of telerehabilitation services to older people. PMID- 26890027 TI - From 1D to 3D: Tunable Sub-10 nm Gaps in Large Area Devices. AB - Tunable sub-10 nm 1D nanogaps are fabricated based on nanoskiving. The electric field in different sized nanogaps is investigated theoretically and experimentally, yielding nonmonotonic dependence and an optimized gap-width (5 nm). 2D nanogap arrays are fabricated to pack denser gaps combining surface patterning techniques. Innovatively, 3D multistory nanogaps are built via a stacking procedure, processing higher integration, and much improved electric field. PMID- 26890028 TI - Correction: PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation. PMID- 26890029 TI - Bark thickness across the angiosperms: more than just fire. AB - Global variation in total bark thickness (TBT) is traditionally attributed to fire. However, bark is multifunctional, as reflected by its inner living and outer dead regions, meaning that, in addition to fire protection, other factors probably contribute to TBT variation. To address how fire, climate, and plant size contribute to variation in TBT, inner bark thickness (IBT) and outer bark thickness (OBT), I sampled 640 species spanning all major angiosperm clades and 18 sites with contrasting precipitation, temperature, and fire regime. Stem size was by far the main driver of variation in thickness, with environment being less important. IBT was closely correlated with stem diameter, probably for metabolic reasons, and, controlling for size, was thicker in drier and hotter environments, even fire-free ones, probably reflecting its water and photosynthate storage role. OBT was less closely correlated with size, and was thicker in drier, seasonal sites experiencing frequent fires. IBT and OBT covaried loosely and both contributed to overall TBT variation. Thickness variation was higher within than across sites and was evolutionarily labile. Given high within-site diversity and the multiple selective factors acting on TBT, continued study of the different drivers of variation in bark thickness is crucial to understand bark ecology. PMID- 26890030 TI - Importance of anisotropy in detachment rates for force production and cargo transport by a team of motor proteins. AB - Many cellular processes are driven by collective forces generated by a team consisting of multiple molecular motor proteins. One aspect that has received less attention is the detachment rate of molecular motors under mechanical force/load. While detachment rate of kinesin motors measured under backward force increases rapidly for forces beyond stall-force; this scenario is just reversed for non-yeast dynein motors where detachment rate from microtubule decreases, exhibiting a catch-bond type behavior. It has been shown recently that yeast dynein responds anisotropically to applied load, i.e. detachment rates are different under forward and backward pulling. Here, we use computational modeling to show that these anisotropic detachment rates might help yeast dynein motors to improve their collective force generation in the absence of catch-bond behavior. We further show that the travel distance of cargos would be longer if detachment rates are anisotropic. Our results suggest that anisotropic detachment rates could be an alternative strategy for motors to improve the transport properties and force production by the team. PMID- 26890031 TI - Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial. AB - Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 +/- 11.84 years) with serum 25 hydroxyvitamin D levels <50 nmol/l (mean 38.89 +/- 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes. PMID- 26890032 TI - A Simple Method for the Size Controlled Synthesis of Stable Oligomeric Clusters of Gold Nanoparticles under Ambient Conditions. AB - Reducing dilute aqueous HAuCl4 with sodium thiocyanate (NaSCN) under alkaline conditions produces 2 to 3 nm diameter nanoparticles. Stable grape-like oligomeric clusters of these yellow nanoparticles of narrow size distribution are synthesized under ambient conditions via two methods. The delay-time method controls the number of subunits in the oligoclusters by varying the time between the addition of HAuCl4 to alkaline solution and the subsequent addition of reducing agent, NaSCN. The yellow oligoclusters produced range in size from ~3 to ~25 nm. This size range can be further extended by an add-on method utilizing hydroxylated gold chloride (Na(+)[Au(OH4-x)Clx](-)) to auto-catalytically increase the number of subunits in the as-synthesized oligocluster nanoparticles, providing a total range of 3 nm to 70 nm. The crude oligocluster preparations display narrow size distributions and do not require further fractionation for most purposes. The oligoclusters formed can be concentrated >300 fold without aggregation and the crude reaction mixtures remain stable for weeks without further processing. Because these oligomeric clusters can be concentrated before derivatization they allow expensive derivatizing agents to be used economically. In addition, we present two models by which predictions of particle size can be made with great accuracy. PMID- 26890034 TI - A Phytic Acid Induced Super-Amphiphilic Multifunctional 3D Graphene-Based Foam. AB - Surfaces with super-amphiphilicity have attracted tremendous interest for fundamental and applied research owing to their special affinity to both oil and water. It is generally believed that 3D graphenes are monoliths with strongly hydrophobic surfaces. Herein, we demonstrate the preparation of a 3D super amphiphilic (that is, highly hydrophilic and oleophilic) graphene-based assembly in a single-step using phytic acid acting as both a gelator and as a dopant. The product shows both hydrophilic and oleophilic intelligence, and this overcomes the drawbacks of presently known hydrophobic 3D graphene assemblies. It can absorb water and oils alike. The utility of the new material was demonstrated by designing a heterogeneous catalytic system through incorporation of a zeolite into its amphiphilic 3D scaffold. The resulting bulk network was shown to enable efficient epoxidation of alkenes without prior addition of a co-solvent or stirring. This catalyst also can be recovered and re-used, thereby providing a clean catalytic process with simplified work-up. PMID- 26890033 TI - Protection against oxidative stress by vitamin D in cone cells. AB - Photoreceptor degeneration (PD) refers to a group of heterogeneous outer retinal dystrophies characterized by the death of photoreceptors. Both oxidative stress and inflammation are involved in the pathogenesis of PD. We investigate whether vitamin D has a potential for the treatment of PD by evaluating the anti oxidative stress and anti-inflammatory properties of the active form of vitamin D3 , 1,alpha, 25-dihydroxyvitamin D3 , in a mouse cone cell line, 661W. Mouse cone cells were treated with H2 O2 or a mixture of H2 O2 and vitamin D; cell viability was determined. The production of reactive oxygen species (ROS) in treated and untreated cells was measured. The expression of key anti-oxidative stress and inflammatory genes in treated and untreated cells was determined. Treatment with vitamin D significantly increased cell viability and decreased ROS production in 661W cells under oxidative stress induced by H2 O2 . H2 O2 treatment in 661W cells can significantly down-regulate the expression of antioxidant genes and up-regulate the expression of neurotoxic cytokines. Vitamin D treatment significantly reversed these effects and restored the expression of antioxidant genes. Vitamin D treatment also can block H2 O2 induced oxidative damages. The data suggested that vitamin D may offer a therapeutic potential for patients with PD. PMID- 26890035 TI - Comparison of Surgical Techniques for Ulnar Collateral Ligament Reconstruction in Overhead Athletes. AB - Several surgical techniques and modifications for ulnar collateral ligament (UCL) reconstruction have been proposed since this procedure was first performed in 1974. The goal of these techniques has been restoration of stability to the medial elbow with minimal alteration to the surrounding anatomy. Outcome studies and systematic reviews on modified techniques for UCL reconstruction have shown a trend toward increased return to play in patients, particularly overhead athletes. Abandonment of flexor pronator mass detachment in favor of a muscle splitting or muscle-elevating approach, minimal handling of the ulnar nerve, and the docking technique may result in improved outcomes and decreased complications without diminished performance. Several biomechanical studies have compared the structural properties of these techniques with those of the native UCL. However, a clear, concise surgical algorithm for UCL reconstruction is lacking. Additional studies that use sport-specific outcome measures and performance metrics may better demonstrate the true return to preinjury performance after UCL reconstruction in overhead athletes. PMID- 26890036 TI - Integrative Medicine in the Department of Defense and the Department of Veterans Affairs: Cautious Steps Forward. PMID- 26890037 TI - Janus gold nanoparticles obtained via spontaneous binary polymer shell segregation. AB - Janus gold nanoparticles are of high interest because they allow directed self assembly and display plasmonic properties. We succeeded in coating gold nanoparticles with two different polymers that form a Janus shell. The spontaneous segregation of two immiscible polymers at the surface of the nanoparticles was verified by NOESY NMR and most importantly by electron microscopy analysis in two and three dimensions. The Janus structure is additionally shown to affect the aggregation behavior of the nanoparticles. PMID- 26890038 TI - Multi-stage inhibition in breast cancer metastasis by orally active triple conjugate, LHTD4 (low molecular weight heparin-taurocholate-tetrameric deoxycholate). AB - Targeting multiple stages in metastatic breast cancer is one of the effective ways to inhibit metastatic progression. To target human metastatic breast cancer as well as improving patient compliance, we developed an orally active low molecular weight heparin (LMWH)-taurocholate conjugated with tetrameric deoxycholic acid, namely LHTD4, which followed by physical complexation with a synthetic bile acid enhancer, DCK. In breast cancer, both transforming growth factor-beta1 (TGF-beta1) and CXCL12 exhibit enhanced metastatic activity during the initiation and progression stages of breast cancer, thus we direct the focus on investigating the antimetastatic effect of LHTD4/DCK complex by targeting TGF beta1 and CXCL12. Computer simulation study and SPR analysis were performed for the binding confirmation of LHTD4 with TGF-beta1 and CXCL12. We carried out in vitro phosphorylation assays of the consecutive receptors of TGF-beta1 and CXCL12 (TGF-beta1R1 and CXCR4, respectively). Effects of LHTD4 on in vitro cell migration (induced by TGF-beta1) and chemotaxis (mediated by CXCL12) were investigated. The in vivo anti-metastatic effect of LHTD4 was evaluated in an accelerated metastasis model and an orthotopic MDA-MB-231 breast cancer model. The obtained KD values of TGF-beta1 and CXCL12 with LHTD4 were 0.85 and 0.019 MUM respectively. The simulation study showed that binding affinities of LHTD4 fragment with either TGF-beta1 or CXCL12 through additional electrostatic interaction was more stable than that of LMWH fragment. In vitro phosphorylation assays of TGF-beta1R1 and CXCR4 showed that the effective inhibition of receptor phosphorylation was observed with the treatment of LHTD4. The expressions of epithelial to mesenchymal transition (EMT) marker proteins such as vimentin and Snail were prevented by LTHD4 treatment in in vitro studies with TGF-beta1 treated MDA-MB-231 cells. Moreover, we observed that LHTD4 negatively regulated the functions of TGF-beta1 and CXCL12 on migration and invasion of breast cancer cell. In several advanced orthotopic and experimental breast cancer metastasis murine models, the treatment with LHTD4 (5 mg/kg daily, p.o.) significantly inhibited metastasis compared to the control. Overall, LHTD4 exhibited anti metastatic effects by inhibiting TGF-beta1 and CXCL12, and the clinically relevant dose of orally active LHTD4 was found to be effective in preclinical studies without any apparent toxicity. PMID- 26890040 TI - Pre-Stent or Not Pre-Stent: That Is the Question!, Editorial Comment for Jessen et al. PMID- 26890042 TI - Parent-informed test-control functional analysis and treatment of problem behavior related to combined establishing operations. AB - PURPOSE: Analog functional analysis (FA) represents the gold standard practice in the functional assessment of problem behavior. In some cases, modifications to typical FA test conditions are required to isolate the environmental variables that evoke and maintain problem behavior. The purpose of the current study was to describe the development of an individualized FA test condition that included combined establishing operations (EOs). METHODS: After an inconclusive standard FA, an individualized FA was conducted based on semi-structured descriptive assessment data collected by parents in the home setting. RESULTS: The individualized test-control combined EO FA produced clearly differentiated results that informed a function-based treatment. CONCLUSIONS: Based on the results of the current study and other similar lines of contemporary research on FA methodology, strategies are discussed for gathering data to inform individualized FA test conditions and derived treatments. PMID- 26890041 TI - Patient-Centered Home Care Using Digital Medicine and Telemetric Data for Hypertension: Feasibility and Acceptability of Objective Ambulatory Assessment. AB - Objective information that can be passively obtained in an ambulatory setting could be potentially useful for determining appropriate care in blood pressure (BP) management. This study utilized digital medicine (DM) prototypes and telemetric data acquisition to directly confirm medication use and to assess habits of daily living in a hypertensive population. Thirty-seven patients (23 men age 62+/-9 years) used the system for 6 weeks. DM prototypes consisted of valsartan 80 mg or 160 mg placed in a gelatin hemicapsule with an excipient tablet as a "stopper," with a poppy seed-sized ingestible sensor (IS) made of foodstuff on its external surface and capable of creating a biogalvanic current on ingestion to alert a wearable sensor (WS) that was worn on the torso. Passive data collection included IS ingestion dates and times, daily step count, BP, and weight. Automatic short message service (SMS) reminders were sent whenever BP or weight values were not received. Passive detection of DM ingestion was 98% when compared with directly observed dosing. Mean taking and timing adherence rates were 90% and 83%, respectively, and the average step count at a pace of >=60 steps per minute was 2.0+/-1.5 h/d. An automatic SMS was sent and 100% confirmed for 251 BP and 14 weight values that were not received. Mild and transient WS related skin irritation was the most common device-related adverse event. There were no serious or unanticipated adverse events. Ninety percent of patients did not mind swallowing a DM capsule, and 75% had a positive overall experience with the system. Ambulatory evaluation of medication adherence and habits of daily living appear to be feasible and acceptable using DM and passive acquisition of telemetric data. PMID- 26890043 TI - Mandarin Tone Identification in Cochlear Implant Users Using Exaggerated Pitch Contours. AB - OBJECTIVE: To determine whether exaggerating the variations in fundamental frequency (F0) contours of Mandarin-based pitch fluctuations could improve tone identification by cochlear implant (CI) users. METHODS: Twelve normal-hearing (NH) listeners and 11 CI users were tested for their ability to recognize F0 contours modeled after Mandarin tones, in 4- or 5-alternatives forced-choice paradigms. Two types of stimuli were used: computer-generated complex tones and voice recordings. Four contours were tested with voice recordings: flat, rise, fall, and dip. A fifth contour, peak, was added for complex tones. The F0 range of each contour was varied in an adaptive manner. A maximum-likelihood technique was used to fit a psychometric function to the performance data and extract threshold at 70% accuracy. RESULTS: As F0 range increased, performance in tone identification improved but did not reach 100% for some CI users, suggesting that confusions between contours could always be made even with extremely exaggerated contours. Compared with NH participants, CI users required substantially larger F0 ranges to identify tones, on the order of 9.3 versus 0.4 semitones. CI users achieved better performance for complex tones than for voice recordings, whereas the reverse was true for NH participants. Confusion matrices showed that the "flat" tone was often a default option when the tone contour's F0 range presented was too narrow for participants to respond correctly. CONCLUSION: These results demonstrate markedly impaired ability for CI users to identify tonal contours, but suggest that the use of exaggerated pitch contours may be helpful for tonal language perception. PMID- 26890044 TI - "Physiological" Ear Clicking: Its Origin and Potential Usability as a Test Tool for the Eustachian Tube Function. AB - OBJECTIVE: To explore the origin of "physiological" ear clicks during deglutition or other pharyngeal movements, which, in contrast to disturbing frequent clicks under pathologic conditions, mostly remain unnoticed by the patient. STUDY DESIGN: Clinical experimental study at a tertiary referral center. METHODS: Ear clicks were recorded by a microphone sealing the external ear canal parallel to endoscopic or manometric evaluations of the Eustachian tube function. RESULTS: Obviously, the acoustic signals (clicks) appear when the tube opens. The clicks might be explained by a disruption of fluid or mucus films covering the mucosa. As in our tests clicks could be recorded regularly, they might potentially be used as indicators in a new tube function test, which has to be elaborated. PMID- 26890039 TI - Extracellular matrix-based biomaterial scaffolds and the host response. AB - Extracellular matrix (ECM) collectively represents a class of naturally derived proteinaceous biomaterials purified from harvested organs and tissues with increasing scientific focus and utility in tissue engineering and repair. This interest stems predominantly from the largely unproven concept that processed ECM biomaterials as natural tissue-derived matrices better integrate with host tissue than purely synthetic biomaterials. Nearly every tissue type has been decellularized and processed for re-use as tissue-derived ECM protein implants and scaffolds. To date, however, little consensus exists for defining ECM compositions or sources that best constitute decellularized biomaterials that might better heal, integrate with host tissues and avoid the foreign body response (FBR). Metrics used to assess ECM performance in biomaterial implants are arbitrary and contextually specific by convention. Few comparisons for in vivo host responses to ECM implants from different sources are published. This review discusses current ECM-derived biomaterials characterization methods including relationships between ECM material compositions from different sources, properties and host tissue response as implants. Relevant preclinical in vivo models are compared along with their associated advantages and limitations, and the current state of various metrics used to define material integration and biocompatibility are discussed. Commonly applied applications of these ECM derived biomaterials as stand-alone implanted matrices and devices are compared with respect to host tissue responses. PMID- 26890045 TI - Prevalence of psoriasis phenotypes among men and women in the USA. AB - BACKGROUND: We present the largest set of US prevalence data for psoriasis to date, obtained from three prospective cohort studies describing validated clinical phenotypes of psoriasis, including novel data about the prevalence of inverse (intertriginous) psoriasis in these groups. Nonplaque psoriasis phenotypes have been largely unmeasured in observational and interventional studies, and this has led to an under-recognition of this aspect of psoriatic disease. AIM: To describe the prevalence of nonplaque psoriasis phenotypes in a large prospective cohort. METHODS: We included 3179 women and 646 men in the analysis. Participants in the Nurses Health Study (NHS) and Health Professionals Follow-up Study (HPFS) with physician-diagnosed psoriasis completed a validated, self-administered questionnaire to assess plaque and nonplaque subsets of psoriasis. RESULTS: Psoriasis phenotypes were as follows: plaque 55%, scalp 52%, palmar-plantar 14%, nail 23% and inverse 21% in the NHS (n = 1604); plaque 60%, scalp 56%, palmar-plantar 16%, nail 27% and inverse 24% in the second NHS study (NHS II) (n = 1575); and plaque 55%, scalp 45%, palmar-plantar 12%, nail 27% and inverse 30% in the HPFS (n = 646). Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis in the USA. CONCLUSION: Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis. PMID- 26890047 TI - Uranyl Ion Complexes with Long-Chain Aliphatic alpha,omega-Dicarboxylates and 3d Block Metal Counterions. AB - Twelve new complexes were obtained from reaction of uranyl ions with the aliphatic dicarboxylic acids HOOC-(CH2)n-2-COOH (H2Cn; n = 7-10 and 12) under solvo-hydrothermal conditions, in the presence of 3d-block metal ions (Mn(2+), Fe(3+), Co(2+), Ni(2+), and Cu(2+)) and 2,2'-bipyridine (bipy) or 1,10 phenanthroline (phen). In contrast to previously reported triple-stranded helicates obtained with C9(2-) and C12(2-), all these complexes crystallize as polymeric one-dimensional (1D) or two-dimensional (2D) species. [Fe(bipy)3][(UO2)2(C7)3].3H2O (1), [Cu(phen)2]2[(UO2)3(C7)4(H2O)2].2H2O (2), and [Cu(bipy)2]2[(UO2)2(C9)3] (6), in which the 3d cation was reduced in situ, are 1D ladderlike polymers displaying tetra- or hexanuclear rings, of sufficient width to encompass two counterions in 2 and 6. The three complexes [Co(phen)3][(UO2)3(C8)3(O)].H2O (3), [Ni(phen)3][(UO2)3(C8)3(O)].H2O (4) and [Co(phen)3][(UO2)3(C9)3(O)].H2O (5) contain bis(MU3-oxo)-bridged tetranuclear secondary building units, and they crystallize as deeply furrowed 2D assemblies. Depending on the nature of the counterion, C10(2-) gives [Ni(bipy)3][(UO2)2(C10)3].2H2O (7), a 2D network displaying elongated decanuclear rings containing the counterions, or [Mn(phen)3][(UO2)2(C10)3].6H2O (8), [Co(phen)3][(UO2)2(C10)3].7H2O (9), and [Ni(phen)3][(UO2)2(C10)3].7H2O (10), which consist of 2D assemblies with honeycomb topology; the hexanuclear rings in 8-10 are chairlike and occupied by one counterion and two uranyl groups from neighboring layers. Two complexes of the ligand with the longest chain, C12(2-), are reported. [UO2(C12)(bipy)] (11) is a neutral 1D species in which bipy chelates the uranyl ion and plays an important role in the packing through pi stacking interactions. Two polymeric units, 1D and 2D, coexist in the complex [Ni(bipy)3][(UO2)2(C12)3][UO2(C12)(H2O)2].H2O (12); the 2D network has the honeycomb topology, but the hexanuclear rings are markedly convoluted, with local features akin to those in helicates, and the counterions are embedded in intralayer cavities. Emission spectra measured in the solid state show in most cases various degrees of quenching, with intense and well-resolved uranyl emission being observed only for complexes 2 and 11. PMID- 26890048 TI - Chelonian perivitelline membrane-bound sperm detection: A new breeding management tool. AB - Perivitelline membrane (PVM)-bound sperm detection has recently been incorporated into avian breeding programs to assess egg fertility, confirm successful copulation, and to evaluate male reproductive status and pair compatibility. Due to the similarities between avian and chelonian egg structure and development, and because fertility determination in chelonian eggs lacking embryonic growth is equally challenging, PVM-bound sperm detection may also be a promising tool for the reproductive management of turtles and tortoises. This study is the first to successfully demonstrate the use of PVM-bound sperm detection in chelonian eggs. Recovered membranes were stained with Hoechst 33342 and examined for sperm presence using fluorescence microscopy. Sperm were positively identified for up to 206 days post-oviposition, following storage, diapause, and/or incubation, in 52 opportunistically collected eggs representing 12 species. However, advanced microbial infection frequently hindered the ability to detect membrane-bound sperm. Fertile Centrochelys sulcata, Manouria emys, and Stigmochelys pardalis eggs were used to evaluate the impact of incubation and storage on the ability to detect sperm. Storage at -20 degrees C or in formalin were found to be the best methods for egg preservation prior to sperm detection. Additionally, sperm derived mtDNA was isolated and PCR amplified from Astrochelys radiata, C. sulcata, and S. pardalis eggs. PVM-bound sperm detection has the potential to substantially improve studies of artificial incubation and sperm storage, and could be used to evaluate the success of artificial insemination in chelonian species. Mitochondrial DNA from PVM-bound sperm has applications for parentage analysis, the study of sperm competition, and potentially species identification. PMID- 26890049 TI - Measuring older women's resilience: Evaluating the suitability of the Connor Davidson Resilience Scale and the Resilience Scale. AB - The author provides conceptual and operational definitions of the construct of resilience in the context of research with older adults (aged 60 years or older). Two psychometric instruments (the Connor-Davidson Resilience Scale and the Resilience Scale) are described. The psychometric properties of each instrument are discussed in relation to the research of the original developers of the tools and research conducted by other investigators. Research on the resilience of older women has yet to be initiated. The author evaluated the psychometric properties of both instruments to determine their suitability for investigation of resilience in older women. PMID- 26890050 TI - The spatial distribution of the photostability of thionine in zeolite L nanochannels investigated by Photobleaching Lifetime Imaging Microscopy. AB - Dye photobleaching is a photochemical reaction that can be investigated locally using fluorescence microscopy techniques. In this study, a user-friendly computational tool to assist photobleaching experiments called Photobleaching Lifetime Imaging Microscopy (PbLIM) is presented. With this tool it is possible to recover the photobleaching kinetics spatially, where a photobleaching lifetime is generated for each pixel of the image. Our model was applied to the photobleaching process of thionine encapsulated into the one-dimensional nano channels of Zeolite L (ZL), from where we gained insight into the molecular oxygen distribution inside the ZL channels, as well as the detailed photobleaching of the confined thionine. PMID- 26890051 TI - Definitions. PMID- 26890046 TI - Value of the 8-oxodG/dG ratio in chronic liver inflammation of patients with hepatocellular carcinoma. AB - The aim of this study was to examine the role of oxidative DNA damage in chronic liver inflammation in the evolution of hepatocellular carcinoma. The accumulated data demonstrated that oxidative DNA damage and chronic liver inflammation are involved in the transformation of normal hepatocytes and their evolution towards hepatocellular carcinoma. However, the levels of 8-oxy-2'-deoxy-guanosine (8 oxodG), a biomarker of oxidative DNA damage, were overestimated and underestimated in previous reports due to various technical limitations. The current techniques are not suitable to analyze the 8-oxodG levels in the non malignant liver tissues and tumors of hepatocellular carcinoma patients unless they are modified. Therefore, in this study, the protocols for extraction and hydrolysis of DNA were optimized using 54 samples from hepatocellular carcinoma patients with various risk factors, and the 8-oxodG and 2'-deoxyguanosine (dG) levels were measured. The patients enrolled in the study include 23 from The Princess Alexandra Hospital and The Royal Brisbane and Women's Hospitals, Brisbane, Australia, and 31 from South Africa. This study revealed that the 8 oxodG/dG ratios tended to be higher in most non-malignant liver tissues compared to hepatocellular carcinoma tissue (p=0.2887). It also appeared that the ratio was higher in non-malignant liver tissue from Southern African patients (p=0.0479), but there was no difference in the 8-oxodG/dG ratios between non malignant liver tissues and tumors of Australian hepatocellular carcinoma patients (p=0.7722). Additionally, this study also revealed a trend for a higher 8-oxodG/dG ratio in non-malignant liver tissues compared to tumoural tissues of patients with HBV. Significant differences were not observed in the 8-oxodG/dG ratios between non-cirrhotic and cirrhotic non-malignant liver tissues. PMID- 26890053 TI - Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication. AB - As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities. PMID- 26890054 TI - Ontogeny of 3D rib curvature and its importance for the understanding of human thorax development. AB - OBJECTIVES: Sagittal and axial rib orientation relative to the spine are two factors that modify rib cage morphology during ontogeny. Some studies suggest that these factors do not operate in the same way at the upper (ribs 1-5) and lower thorax (ribs 6-10) during postnatal growth, but it is unknown if the ontogenetic thoracic changes are produced by morphological changes of the ribs (intrinsic rib factors) or by external factors related to costal joints (extrinsic rib factors). MATERIAL AND METHODS: To clarify these questions, we applied 3D geometric morphometrics of landmarks and sliding semilandmarks (N = 20/rib) to 280 individual ribs (1-10) of Homo sapiens comprising the entire human ontogeny and growth simulations were carried out. RESULTS: PCA shows that intrinsic rib factors (rib torsion and axial rib curvature) are ontogenetic factors of variability that contribute to configuring the adult thorax shape. Moreover, growth simulations and regression slopes suggest that the upper thorax unit is comprised by ribs 1-7 and the lower unit at least by ribs 8-10. DISCUSSION: These results suggest anatomical constraints for ontogenetic rib variation, since ribs 1-7 (true ribs) are directly linked to the sternum. Moreover, these results are supported by functional anatomy because pulmonary kinematics would influence the upper unit and diaphragmatic kinematics would influence the lower one. Our findings are relevant not only to understanding how changes at individual ribs contribute to the adult thorax morphology, but also to the development and evolution of the modern human rib cage. PMID- 26890055 TI - Erratum: Body mass estimation from knee breadth, with application to early hominins. By Nicole Squyres and Christopher B. Ruff Am J Phys Anthropol 158:198 208, 2015. DOI: 10.1002/ajpa.22789. AB - In the above-referenced article, on p. 200, it was stated that data were natural log-transformed for RMA regressions. In fact, all regressions - RMA as well as LS - were carried out on raw data, as stated earlier in the paper.We apologize for any confusion this error might have caused. PMID- 26890056 TI - Proceedings of the Eighty-Fourth Business Meeting of the American Association of Physical Anthropologists St. Louis, Missouri March 25-28, 2015. PMID- 26890058 TI - Analyzing the relationships between travel mode indicators and the number of passenger transport fatalities at the city level. AB - OBJECTIVE: A number of efforts have been conducted on travel behavior and transport fatalities at the neighborhood or street level, and they have identified different factors such as roadway characteristics, personal indicators, and design indicators related to transport safety. However, only a limited number of studies have considered the relationship between travel behavior indicators and the number of transport fatalities at the city level. Therefore, this study explores this relationship and how to fill the mentioned gap in current knowledge. METHOD: A generalized linear model (GLM) estimates the relationships between different travel mode indicators (e.g., length of motorway per inhabitants, number of motorcycles per inhabitant, percentage of daily trips on foot and by bicycle, percentage of daily trips by public transport) and the number of passenger transport fatalities. Because this city-level model is developed using data sets from different cities all over the world, the impacts of gross domestic product (GDP) are also included in the model. CONCLUSIONS: Overall, the results imply that the percentage of daily trips by public transport, the percentage of daily trips on foot and by bicycle, and the GDP per inhabitant have negative relationships with the number of passenger transport fatalities, whereas motorway length and the number of motorcycles have positive relationships with the number of passenger transport fatalities. PMID- 26890059 TI - Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015. AB - Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3). PMID- 26890061 TI - Mycobacterium microti Infection in Dairy Goats, France. PMID- 26890060 TI - Patient Report and Review of Rapidly Growing Mycobacterial Infection after Cardiac Device Implantation. AB - Mycobacterial infections resulting from cardiac implantable electronic devices are rare, but as more devices are implanted, these organisms are increasingly emerging as causes of early-onset infections. We report a patient with an implantable cardioverter-defibrillator pocket and associated bloodstream infection caused by an organism of the Mycobacterium fortuitum group, and we review the literature regarding mycobacterial infections resulting from cardiac device implantations. Thirty-two such infections have been previously described; most (70%) were caused by rapidly growing species, of which M. fortuitum group species were predominant.When managing such infections, clinicians should consider the potential need for extended incubation of routine cultures or dedicated mycobacterial cultures for accurate diagnosis; combination antimicrobial drug therapy, even for isolates that appear to be macrolide susceptible, because of the potential for inducible resistance to this drug class; and the arrhythmogenicity of the antimicrobial drugs traditionally recommended for infections caused by these organisms. PMID- 26890062 TI - Graphene engineering by neon ion beams. AB - Achieving the ultimate limits of lithographic resolution and material performance necessitates engineering of matter with atomic, molecular, and mesoscale fidelity. With the advent of scanning helium ion microscopy, maskless He(+) and Ne(+) beam lithography of 2D materials, such as graphene-based nanoelectronics, is coming to the forefront as a tool for fabrication and surface manipulation. However, the effects of using a Ne focused-ion-beam on the fidelity of structures created out of 2D materials have yet to be explored. Here, we will discuss the use of energetic Ne ions in engineering graphene nanostructures and explore their mechanical, electromechanical and chemical properties using scanning probe microscopy (SPM). By using SPM-based techniques such as band excitation (BE) force modulation microscopy, Kelvin probe force microscopy (KPFM) and Raman spectroscopy, we are able to ascertain changes in the mechanical, electrical and optical properties of Ne(+) beam milled graphene nanostructures and surrounding regions. Additionally, we are able to link localized defects around the milled graphene to ion milling parameters such as dwell time and number of beam passes in order to characterize the induced changes in mechanical and electromechanical properties of the graphene surface. PMID- 26890063 TI - CCL20/CCR6 Signaling Regulates Bone Mass Accrual in Mice. AB - CCL20 is a member of the macrophage inflammatory protein family and is reported to signal monogamously through the receptor CCR6. Although studies have identified the genomic locations of both Ccl20 and Ccr6 as regions important for bone quality, the role of CCL20/CCR6 signaling in regulating bone mass is unknown. By micro-computed tomography (MUCT) and histomorphometric analysis, we show that global loss of Ccr6 in mice significantly decreases trabecular bone mass coincident with reduced osteoblast numbers. Notably, CCL20 and CCR6 were co expressed in osteoblast progenitors and levels increased during osteoblast differentiation, indicating the potential of CCL20/CCR6 signaling to influence osteoblasts through both autocrine and paracrine actions. With respect to autocrine effects, CCR6 was found to act as a functional G protein-coupled receptor in osteoblasts and although its loss did not appear to affect the number or proliferation rate of osteoblast progenitors, differentiation was significantly inhibited as evidenced by delays in osteoblast marker gene expression, alkaline phosphatase activity, and mineralization. In addition, CCL20 promoted osteoblast survival concordant with activation of the PI3K-AKT pathway. Beyond these potential autocrine effects, osteoblast-derived CCL20 stimulated the recruitment of macrophages and T cells, known facilitators of osteoblast differentiation and survival. Finally, we generated mice harboring a global deletion of Ccl20 and found that Ccl20(-/-) mice exhibit a reduction in bone mass similar to that observed in Ccr6(-/-) mice, confirming that this phenomenon is regulated by CCL20 rather than alternate CCR6 ligands. Collectively, these data indicate that CCL20/CCR6 signaling may play an important role in regulating bone mass accrual, potentially by modulating osteoblast maturation, survival, and the recruitment of osteoblast-supporting cells. (c) 2016 American Society for Bone and Mineral Research. PMID- 26890064 TI - Solitary cannabis use frequency mediates the relationship between social anxiety and cannabis use and related problems. AB - BACKGROUND AND OBJECTIVES: Individuals with elevated social anxiety are seven times more likely to meet criteria for cannabis use disorders, yet social anxiety is unrelated to more frequent cannabis use. The lack of relation to cannabis use frequency may be at least partially due to lack of attention to cannabis use context. It may be that socially anxious persons engage in frequent solitary cannabis use, perhaps using before social situations in the hope that being intoxicated during the social event will help them feel less anxious. In fact, using cannabis alone has been associated with experiencing more cannabis-related problems in prior work. METHODS: The current study sought to identify whether solitary cannabis use frequency mediated the relationship between social anxiety and cannabis-related problems among 276 current cannabis using undergraduates who completed an online survey of putative predictors of substance use. RESULTS: Social anxiety was robustly related to more frequent solitary (but not social) cannabis use and solitary cannabis use frequency uniquely mediated the relation of social anxiety to cannabis use and related problems. DISCUSSION AND CONCLUSIONS: Frequent solitary use appears to play an important role in the experience of cannabis-related problems among socially anxious persons. SCIENTIFIC SIGNIFICANCE: Intervention strategies may benefit from targeting frequent solitary cannabis use, particularly among at-risk users such as those with elevated social anxiety. PMID- 26890065 TI - Interprofessional education in an enrichment programme for prospective health sciences students. AB - Effective and meaningful interprofessional education opportunities for prospective health sciences students are important to prepare students for the work environment they will encounter after training. This article briefly describes the Summer Academic Enrichment Program, a programme for students pursuing entry to dentistry, medicine, pharmacy, and physical therapy schools. The programme evaluation includes investigation of the programme's effectiveness to impact attitudes towards interprofessional teams and collaboration. The Attitudes Toward Health Care Teams Scale and the Revised Readiness for Interprofessional Learning Scale were administered at the beginning and the end of the programme. Statistical analysis of pre-assessment subscale scores indicated that pre-pharmacy students reported significantly more positive attitudes towards team value than pre-dental students at the beginning of the programme, with post-assessment results indicating that these differences had been eliminated. Additionally, all students demonstrated significantly more positive attitudes towards interprofessional teams during the post-assessment. PMID- 26890066 TI - Self-report depressive symptoms do not directly predict suicidality in nonclinical individuals: Contributions toward a more psychosocial approach to suicide risk. AB - Although suicidality is associated with mental illness in general and depression in particular, many depressed individuals do not attempt suicide and some individuals who attempt to or do die by suicide do not present depressive symptoms. This article aims to contribute to a more psychosocial approach to understanding suicide risk in nonclinical populations. In advocating a psychosocial perspective rather than a depression-focused approach, this article presents four diverse studies that demonstrate sampling and measurement invariance in findings across different populations and specific measures. Study 1 tests the mediation effects of 2 interpersonal variables, thwarted belongingness and perceived burdensomeness, in the association between depressive symptoms and recent suicidality. Studies 2 and 3 evaluate the contribution of hopelessness and psychache, beyond depressive symptoms, to suicidality. Study 4 tests the contribution of life events behind depressive symptoms, and other relevant sociodemographic and clinical variables, to the estimation of "future suicidality." Overall, results demonstrate that depressive symptoms do not directly predict suicidality in nonclinical individuals, but that other psychosocial variables mediate the association between depressive symptoms and suicidality or predict suicidality when statistically controlling for depressive symptoms. The article contributes to understanding some of the nonpsychopathological factors that potentially link depressive symptoms to suicide risk and that might themselves contribute to suicidality, even when controlling for depressive symptoms. PMID- 26890067 TI - Implications of plant glycans in the development of innovative vaccines. AB - Plant glycans play a central role in vaccinology: they can serve as adjuvants and/or delivery vehicles or backbones for the synthesis of conjugated vaccines. In addition, genetic engineering is leading to the development of platforms for the production of novel polysaccharides in plant cells, an approach with relevant implications for the design of new types of vaccines. This review contains an updated outlook on this topic and provides key perspectives including a discussion on how the molecular pharming field can be linked to the production of innovative glycan-based and conjugate vaccines. PMID- 26890068 TI - A link between the driver mutations and dysregulated apoptosis in BCR-ABL1 negative myeloproliferative neoplasms. AB - The current understanding of BCR-ABL1 negative myeloproliferative neoplasms pathogenesis is centred on the phenotypic driver mutations in JAK2, MPL, or CALR genes, and the constitutive activation of JAK-STAT pathway. Nonetheless, there is still a need to better characterize the cellular processes that are triggered by these genetic alterations, such as apoptosis that might play a role in the pathological expansion of the myeloid lineages and, especially, in the morphological anomalies of the bone marrow megakaryocytes. In this article we will explore the connection between the driver mutations in MPN and the abnormal apoptosis that might be translated in new therapeutic strategies. PMID- 26890069 TI - Fuzhuan tea consumption imparts hepatoprotective effects and alters intestinal microbiota in high saturated fat diet-fed rats. AB - SCOPE: Nonalcoholic fatty liver disease is an obesity-related disorder characterized by lipid infiltration of the liver. Management is limited to lifestyle modifications, highlighting the need for alternative therapeutic options. The objective of this study was to examine if fermented Fuzhuan tea prevents metabolic impairments associated with development of hepatic steatosis. METHODS AND RESULTS: Rats consumed control (CON) or high saturated fat (SAT) diets with or without Fuzhuan tea for 8 weeks. Outcomes included enzymatic and gene expression measures of metabolic dysregulation in liver and adipose tissue. Pyrosequencing was used to assess intestinal microbiota adaptations. Fuzhuan tea prevented diet-induced inflammation in the liver. Liver triglycerides of ~18 mg/g were observed in SAT-fed animals, but remained similar to CON diet levels (~12 mg/g) when supplemented with Fuzhuan tea. In adipose tissue, tea treatment prevented SAT-induced inflammation and reduced plasma leptin approximately twofold. Fuzhuan tea also altered intestinal function and was associated with a threefold increase in two Lactobacillus spp. CONCLUSIONS: These data suggest that Fuzhuan tea protects against liver and adipose tissue stress induced by a high SAT diet and positively influences intestinal function. Further investigation of the molecular targets of Fuzhuan tea is warranted. PMID- 26890070 TI - Cytokinetic effects of Wee1 disruption in pancreatic cancer. AB - The Wee1 kinase, which is activated in response to DNA damage, regulates exit from G2 through inhibitory phosphorylation of Cdk1/Cdc2, and is an attractive drug target. However, recent work has highlighted effects of Cdk2 phosphorylation by Wee1 on movement through S-phase, suggesting the potential to sensitize to S phase specific agents by Wee1 inhibitors. In this paper we applied multiparametric flow cytometry to patient-derived pancreatic cancer xenograft tumor cells to study the cell cycle perturbations of Wee1 disruption via the small molecule inhibitor MK-1775, and genetic knockdown. We find that in vitro treatment with MK-1775, and to a lesser degree, Wee1 RNA transcript knockdown, results in the striking appearance of S-phase cells prematurely entering into mitosis. This effect was not seen in vivo in any of the models tested. Here, although we noted an increase of S-phase cells expressing the damage response marker gammaH2AX, treatment with MK-1775 did not significantly sensitize cells to the cytidine analog gemcitabine. Treatment with MK-1775 did result in a transient but large increase in cells expressing the mitotic marker phosphorylated H3S10 that reached a peak 4 hours after treatment. This suggests a role for Wee1 regulating the progression of genomically unstable cancer cells through G2 in the absence of extrinsically-applied DNA damage. A single dose of 8Gy ionizing radiation resulted in the time-dependent accumulation of Cyclin A2 positive/phosphorylated H3S10 negative cells at the 4N position, which was abrogated by treatment with MK-1775. Consistent with these findings, a genome scale pooled RNA interference screen revealed that toxic doses of MK-1775 are suppressed by CDK2 or Cyclin A2 knockdown. These findings support G2 exit as the more significant effect of Wee1 inhibition in pancreatic cancers. PMID- 26890072 TI - Short Flow-Photochemistry Enabled Synthesis of the Cytotoxic Lactone (+) Goniofufurone. AB - A photochemical approach to the cytotoxic lactone (+)-goniofufurone (1) is reported. Paterno-Buchi [2 + 2] photocycloaddition from known enol ether 4, derived from the readily available sugar d-isosorbide, yielded oxetane 7. This slow, dilute reaction was scaled up by using flow photochemistry to yield >40 g of 7. Installation of the key lactone ring was achieved via a unique Wacker-style oxidation of an enol-ether bond. Acid-catalyzed aqueous ring opening provided 1 in five steps from 4 (11.5% overall). PMID- 26890071 TI - Optimizing Mouse Surgery with Online Rectal Temperature Monitoring and Preoperative Heat Supply. Effects on Post-Ischemic Acute Kidney Injury. AB - Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret 3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that <1% of the temperature readings were within the target range of 36.5 to 38.5 degrees C. Setup B and C increased the target range readings to 34.6 +/- 28.0% and 99.3 +/- 1.5%, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes. PMID- 26890073 TI - Genetic Analysis of IL-17 Gene Polymorphisms in Gout in a Male Chinese Han Population. AB - Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL 17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: chi2 = 0.15, p = 0.928 by genotype, chi2 = 0.14, p = 0.711 by allele; rs763780: chi2 = 2.24, p = 0.326 by genotype, chi2 = 0.26, p = 0.609 by allele; rs4819554: chi2 = 1.79, p = 0.409 by genotype, chi2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation. PMID- 26890074 TI - Variations in T Cell Transcription Factor Sequence and Expression Associated with Resistance to the Sheep Nematode Teladorsagia circumcincta. AB - This study used selected lambs that varied in their resistance to the gastrointestinal parasite Teladorsagia circumcincta. Infection over 12 weeks identified susceptible (high adult worm count, AWC; high fecal egg count, FEC; low body weight, BW; low IgA) and resistant sheep (no/low AWC and FEC, high BW and high IgA). Resistance is mediated largely by a Th2 response and IgA and IgE antibodies, and is a heritable characteristic. The polarization of T cells and the development of appropriate immune responses is controlled by the master regulators, T-bet (TBX21), GATA-3 (GATA3), RORgammat (RORC2) and RORalpha (RORA); and several inflammatory diseases of humans and mice are associated with allelic or transcript variants of these transcription factors. This study tested the hypothesis that resistance of sheep to T. circumcincta is associated with variations in the structure, sequence or expression levels of individual master regulator transcripts. We have identified and sequenced one variant of sheep TBX21, two variants of GATA3 and RORC2 and five variants of RORA from lymph node mRNA. Relative RT-qPCR analysis showed that TBX21, GATA3 and RORC2 were not significantly differentially-expressed between the nine most resistant (AWC, 0; FEC, 0) and the nine most susceptible sheep (AWC, mean 6078; FEC, mean 350). Absolute RT-qPCR on 29 all 45 animals identified RORAv5 as being significantly differentially-expressed (p = 0.038) 30 between resistant, intermediate and susceptible groups; RORAv2 was not differentially- 31 expressed (p = 0.77). Spearman's rank analysis showed that RORAv5 transcript copy number 32 was significantly negatively correlated with parameters of susceptibility, AWC and FEC; and 33 was positively correlated with BW. RORAv2 was not correlated with AWC, FEC or BW but 34 was significantly negatively correlated with IgA antibody levels [corrected]. This study identifies the full length RORA variant (RORAv5) as important in controlling the protective immune response to T. circumcincta infection in sheep. PMID- 26890077 TI - A comprehensive conceptual framework for road safety strategies. AB - Road safety strategies (generally called Strategic Highway Safety Plans in the USA) provide essential guidance for actions to improve road safety, but often lack a conceptual framework that is comprehensive, systems theory based, and underpinned by evidence from research and practice. This paper aims to incorporate all components, policy tools by which they are changed, and the general interactions between them. A framework of nine mutually interacting components that contribute to crashes and ten generic policy tools which can be applied to reduce the outcomes of these crashes was developed and used to assess 58 road safety strategies from 22 countries across 15 years. The work identifies the policy tools that are most and least widely applied to components, highlighting the potential for improvements to any individual road safety strategy, and the potential strengths and weaknesses of road safety strategies in general. The framework also provides guidance for the development of new road safety strategies, identifying potential consequences of policy tool based measures with regard to exposure and risk, useful for both mobility and safety objectives. PMID- 26890076 TI - Glycation Reactivity of a Quorum-Sensing Signaling Molecule. AB - Reported herein is that (4S)-4,5-dihydroxy-2,3-pentanedione (DPD) can undergo a previously undocumented non-enzymatic glycation reaction. Incubation of DPD with viral DNA or the antibiotic gramicidin S resulted in significant biochemical alterations. A protein-labeling method was consequently developed that facilitated the identification of unrecognized glycation targets of DPD in a prokaryotic system. These results open new avenues toward tracking and understanding the fate and function of the elusive quorum-sensing signaling molecule. PMID- 26890079 TI - Without Binding ATP, Human Rad51 Does Not Form Helical Filaments on ssDNA. AB - Construction of the presynaptic filament (PSF) of proper helical structure by Rad51 recombinases is a prerequisite of the progress of homologous recombination repair. We studied the contribution of ATP-binding to this structure of wt human Rad51 (hRad51). We exploited the protein-dissociation effect of high hydrostatic pressure to determine the free energy of dissociation of the protomer interfaces in hRad51 oligomer states and used electron microscopy to obtain topological parameters. Without cofactors ATP and Ca(2+) and template DNA, hRad51 did not exist in monomer form, but it formed rodlike long filaments without helical order. DeltaG(diss) indicated a strong inherent tendency of aggregation. Binding solely ssDNA left the filament unstructured with slightly increased DeltaG(diss). Adding only ATP and Ca(2+) to the buffer disintegrated the self-associated rods into rings and short helices of further increased DeltaG(diss). Rad51 binding to ssDNA only with ATP and Ca bound could lead to ordered helical filament formation of proper pitch size with interface contacts of K(d) ~ 2 * 10(-11) M, indicating a structure of outstanding stability. ATP/Ca binding increased the DeltaG(diss) of protomer contacts in the filament by 16 kJ/mol. The results emphasize that ATP binding in the PSF of hRad51 has an essential, yet purely structural, role. PMID- 26890084 TI - More effort - more results: recent advances in integrative 'omics' data analysis. AB - The development of 'omics' technologies has progressed to address complex biological questions that underlie various plant functions thereby producing copious amounts of data. The need to assimilate large amounts of data into biologically meaningful interpretations has necessitated the development of statistical methods to integrate multidimensional information. Throughout this review, we provide examples of recent outcomes of 'omics' data integration together with an overview of available statistical methods and tools. PMID- 26890078 TI - The role of Body Mass Index in child pedestrian injury risk. AB - The goal of the current investigation was to examine obesity as a potential risk factor for childhood pedestrian injury. A racially diverse sample of 7- and 8 year-old children completed a road-crossing task in a semi-immersive virtual environment and two pedestrian route selection tasks. Multiple linear regression analyses revealed that children with a higher Body Mass Index (BMI) waited less before crossing, had a smaller temporal buffer between themselves and oncoming traffic while crossing, and had more collisions with traffic. Girls were more cautious than boys when crossing the virtual roadway. Unlike the results from the virtual road-crossing task, BMI was not associated with risky route selection. Instead, race emerged as the strongest predictor, with African-American children selecting riskier routes for crossing. Together, these findings suggest overweight and obese children may be at increased risk for pedestrian injury. The discussion considers explanations for why obese children may exhibit riskier road crossing behavior. PMID- 26890085 TI - Patient-centered care for left ventricular assist device therapy: current challenges and future directions. AB - PURPOSE OF REVIEW: Discuss the current status and obstacles that need to be overcome in the future to provide patient-centered care with left ventricular assist device (LVAD) therapy. RECENT FINDINGS: LVADs offer both longer survival and improvements in quality of life for carefully selected patients with inotrope dependent heart failure. Yet, this technology does not come without significant risk of adverse effects and burdens. Recent observational data comparing LVAD with medical therapy in ambulatory, noninotrope-dependent patients with advanced heart failure suggest that survival may be similar and changes in quality of life may depend on baseline status. As both LVAD technology and medical therapy continue to evolve, there are many unanswered questions regarding the benefits, risks, and burdens of LVAD therapies in less severe heart failure populations. SUMMARY: Further research is needed to ensure the optimal delivery of LVAD therapy, including improved patient selection, implantation timing, device type, and decision support. VIDEO ABSTRACT. PMID- 26890087 TI - Topographical and Chemical Imaging of a Phase Separated Polymer Using a Combined Atomic Force Microscopy/Infrared Spectroscopy/Mass Spectrometry Platform. AB - In this paper, the use of a hybrid atomic force microscopy/infrared spectroscopy/mass spectrometry imaging platform was demonstrated for the acquisition and correlation of nanoscale sample surface topography and chemical images based on infrared spectroscopy and mass spectrometry. The infrared chemical imaging component of the system utilized photothermal expansion of the sample at the tip of the atomic force microscopy probe recorded at infrared wave numbers specific to the different surface constituents. The mass spectrometry based chemical imaging component of the system utilized nanothermal analysis probes for thermolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. The basic instrumental setup, operation, and image correlation procedures are discussed, and the multimodal imaging capability and utility are demonstrated using a phase separated poly(2-vinylpyridine)/poly(methyl methacrylate) polymer thin film. The topography and both the infrared and mass spectral chemical images showed that the valley regions of the thin film surface were comprised primarily of poly(2-vinylpyridine) and hill or plateau regions were primarily poly(methyl methacrylate). The spatial resolution of the mass spectral chemical images was estimated to be 1.6 MUm based on the ability to distinguish surface features in those images that were also observed in the topography and infrared images of the same surface. PMID- 26890086 TI - Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p. AB - To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. The i(12p)-positive cells displayed a characteristic expression and methylation signature. Of all the genes on 12p, 13% were overexpressed, including the ATN1, COPS7A, and NECAP1 genes in 12p13.31, a region previously implicated in PKS. However, the median expression fold change (1.3) on 12p was lower than expected by tetrasomy 12p. Thus, partial dosage compensation occurs in cells with i(12p). The majority (89%) of the significantly deregulated genes were not situated on 12p, indicating that global perturbation of gene expression is a key pathogenetic event in PKS. Three genes-ATP6V1G1 in 9q32, GMPS in 3q25.31, and TBX5 in 12q24.21-exhibited concomitant hypermethylation and decreased expression. The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. We hypothesize that this non-genic hypomethylation is associated with chromatin processing that facilitates cellular adaptation to excess genetic material. PMID- 26890089 TI - A Game-Theoretical Model to Improve Process Plant Protection from Terrorist Attacks. AB - The New York City 9/11 terrorist attacks urged people from academia as well as from industry to pay more attention to operational security research. The required focus in this type of research is human intention. Unlike safety-related accidents, security-related accidents have a deliberate nature, and one has to face intelligent adversaries with characteristics that traditional probabilistic risk assessment techniques are not capable of dealing with. In recent years, the mathematical tool of game theory, being capable to handle intelligent players, has been used in a variety of ways in terrorism risk assessment. In this article, we analyze the general intrusion detection system in process plants, and propose a game-theoretical model for security management in such plants. Players in our model are assumed to be rational and they play the game with complete information. Both the pure strategy and the mixed strategy solutions are explored and explained. We illustrate our model by an illustrative case, and find that in our case, no pure strategy but, instead, a mixed strategy Nash equilibrium exists. PMID- 26890088 TI - Metabolic Response of Strawberry (Fragaria x ananassa) Leaves Exposed to the Angular Leaf Spot Bacterium (Xanthomonas fragariae). AB - Plants have evolved various defense mechanisms against biotic stress. The most common mechanism involves the production of metabolites that act as defense compounds. Bacterial angular leaf spot disease (Xanthomonas fragariae) of the strawberry (Fragaria x ananassa) has become increasingly destructive to strawberry leaves and plant production. In this study, we examined metabolic changes associated with the establishment of long-term bacterial disease stress using UPLC-QTOF mass spectrometry. Infected leaves showed decreased levels of gallic acid derivatives and ellagitannins, which are related to the plant defense system. The levels of phenylalanine, tryptophan, and salicylic acid as precursors of aromatic secondary metabolites were increased in inoculated leaves, whereas levels of coumaric acid, quinic acid, and flavonoids were decreased in infected plants, which are involved in the phenylpropanoid pathway. In addition, phenylalanine ammonia-lyase (PAL) activity, a key enzyme in the phenylpropanoid pathway, was decreased following infection. These results suggest that long-term bacterial disease stress may lead to down-regulation of select molecules of the phenylpropanoid metabolic pathway in strawberry leaves. This approach could be applied to explore the metabolic pathway associated with plant protection/breeding in strawberry leaves. PMID- 26890090 TI - Fatty acid vesicles acting as expanding horizon for transdermal delivery. AB - The body is protected against the external environment by the skin due to its physical barrier nature. Stratum corneum composed of corneocytes surrounded by lipid region performs a major barrier function as it lies in the uppermost area of skin. Alteration in barrier function, increase in permeability, and disorganization of stratum corneum represent diseased skin. Drugs applied to the diseased skin should induce a local effect at the site of application or area close to it along with cutaneous absorption rather than percutaneous absorption. Conventional formulations like ointments, gels, and creams suffer from the drawback of limited local activity. For the enhancement of drug penetration and localization of the drug at the site of action approaches explored are liposomes, niosomes, ethosomes microparticles, and solid lipid nanoparticles. Vesicles composed of fatty acids like oleic acid and linoleic acid represent the new approach used for transdermal penetration and localization. In this review article, our major aim was to explore the applications of fatty acid vesicles for transdermal delivery of various bioactives. PMID- 26890091 TI - Development and optimization of a sensitive TaqMan(r) real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load. AB - Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan(r) real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan(r) PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan(r) real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890092 TI - Self-Assembly of Polyethylene Glycol-Grafted Carbon Nanotube/Sulfur Composite with Nest-like Structure for High-Performance Lithium-Sulfur Batteries. AB - The novel polyethylene glycol-grafted multiwalled carbon nanotube/sulfur (PEG CNT/S) composite cathodes with nest-like structure are fabricated through a facile combination process of liquid phase deposition and self-assembly, which consist of the active material core of sulfur particle and the conductive shell of PEG-CNT network. The unique architecture not only provides a short and rapid charge transfer pathway to improve the reaction kinetics but also alleviates the volume expansion of sulfur during lithiation and minimizes the diffusion of intermediate polysulfides. Such an encouraging electrochemical environment ensures the excellent rate capability and high cycle stability. As a result, the as-prepared PEG-CNT/S composite with sulfur content of 75.9 wt % delivers an initial discharge capacity of 1191 and 897 mAh g(-1) after 200 cycles at 0.2 C with an average Coulombic efficiency of 99.5%. Even at a high rate of 2 C, an appreciable capacity of 723 mAh g(-1) can still be obtained. PMID- 26890093 TI - Grasping objects by former amputees: The visuo-motor control of allografted hands. AB - PURPOSE: Hand allograft has recently emerged as a therapeutic option for upper limb amputees. Functional neuroimaging studies have progressively revealed sensorimotor cortices plasticity following both amputation and transplantation. The purpose of our study was to assess and characterize the functional recovery of the visuo-motor control of prehension in bilateral hand transplanted patients. METHODS: Using kinematics recordings, we characterized the performance of prehension with or without visual feed-back for object of different position and size, in five bilateral hand allograft recipients and age-matched control subjects. Both hands were assessed, separately. RESULTS: Despite an overall slower execution, allografted patients succeeded in grasping for more than 90% of the trials. They exhibited a preserved hand grip scaling according to object size, and preserved prehension performances when tested without visual feedback. These findings highlight the allograft recipients' abilities to produce an effective motor program, and a good proprioceptive-dependent online control. Nevertheless, the maximum grip aperture was reduced and delayed, the coupling between Transport and Grasp components was altered, and the final phase of the movement was lengthened. CONCLUSION: Hand allotransplantation can offer recipients a good recovery of the visuo-motor control of prehension, with slight impairments likely attributable to peripheral neuro-orthopedic limitations. PMID- 26890094 TI - Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus. AB - PURPOSE: Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS). METHODS: Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response. RESULTS: Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group. CONCLUSIONS: In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials. PMID- 26890095 TI - Effects of transcranial random noise stimulation (tRNS) on affect, pain and attention in multiple sclerosis. AB - PURPOSE: Pain and cognitive impairment are frequent symptoms in patients with multiple sclerosis (MS). Neglecting experimental pain and paying attention to demanding tasks is reported to decrease the pain intensity. Little is known about the interaction between chronic neuropathic pain and attention disorders in MS. Recently, transcranial direct current stimulation (tDCS) was used to modulate various cognitive and motor symptoms in MS. We aimed to study the effects of transcranial random noise stimulation (tRNS), a form of transcranial electric stimulation, over the left dorsolateral prefrontal cortex (DLPFC) on attention and neuropathic pain in MS patients. METHODS: 16 MS patients were included in a randomized, sham-controlled, cross-over study. Each patient randomly received two tRNS blocks, separated by three weeks of washout interval. Each block consisted of three consecutive daily sessions of either active or sham tRNS. The patients were evaluated for pain, attention and mood and further underwent an electrophysiological evaluation. RESULTS: Compared to sham, tRNS showed a trend to decrease the N2-P2 amplitudes of pain related evoked potentials and improve pain ratings. Attention performance and mood scales did not change after stimulations. CONCLUSIONS: This study suggests the role of tRNS in pain modulation, which could have been more evident with longer stimulation protocols. PMID- 26890096 TI - Evidence for reading improvement following tDCS treatment in children and adolescents with Dyslexia. AB - PURPOSE: There is evidence that non-invasive brain stimulation transitorily modulates reading by facilitating the neural pathways underactive in individuals with dyslexia. The study aimed at investigating whether multiple sessions of transcranial direct current stimulation (tDCS) would enhance reading abilities of children and adolescents with dyslexia and whether the effect is long-lasting. METHODS: Eighteen children and adolescents with dyslexia received three 20-minute sessions a week for 6 weeks (18 sessions) of left anodal/right cathodal tDCS set at 1 mA over parieto-temporal regions combined with a cognitive training. The participants were randomly assigned to the active or the sham treatment; reading tasks (text, high and low frequency words, non-words) were used as outcome measures and collected before treatment, after treatment and one month after the end of treatment. The tolerability of tDCS was evaluated. RESULTS: The active group showed reduced low frequency word reading errors and non-word reading times. These positive effects were stable even one month after the end of treatment. None reported adverse effects. CONCLUSIONS: The study shows preliminary evidence of tDCS feasibility and efficacy in improving non-words and low frequency words reading of children and adolescents with dyslexia and it opens new rehabilitative perspectives for the remediation of dyslexia. PMID- 26890098 TI - Kinematic measures for upper limb motor assessment during robot-mediated training in patients with severe sub-acute stroke. AB - PURPOSE: Kinematic assessments are increasingly used as motor outcome measures during upper limb robot-assisted training, in addition to clinical scales. However, their relevance has not been evaluated much. METHODS: Thirty-eight patients with severe sub-acute stroke (age 56 +/- 17 [19-87] years; time since stroke, 55 +/- 22 days) carried out 16 sessions (average 3/week, 35 +/- 15 days) of upper limb robot-assisted training combined with standard therapy. Pre/post motor performance was evaluated using the Fugl-Meyer Assessment scale, Motor Status Scale (MSS) and kinematic measures. Motor outcomes were compared and relationships between clinical and kinematic outcomes were analyzed. RESULTS: All clinical and kinematic outcomes improved after training (p < 0.01). FM score increased from 17.7 +/- 10.0 to 28.6 +/- 15.4. All baseline kinematic measures were strongly correlated with clinical scores. Correlations between clinical and kinematic changes were moderate (r = -0.65 for change in FM Proximal score and change in accuracy measure). However, smoothness and accuracy indicators were shown to be responsive measures. CONCLUSION: This study demonstrated that baseline kinematic measures and their pre/post training changes were significantly correlated with clinical motor outcome measures. However, even if kinematic measures are valid for the evaluation of motor impairment we cannot propose to substitute common clinical measures of motor function which also evaluate functional abilities of the upper limb. PMID- 26890097 TI - Interactive virtual feedback improves gait motor imagery after spinal cord injury: An exploratory study. AB - PURPOSE: Motor imagery can improve motor function and reduce pain. This is relevant to individuals with spinal cord injury (SCI) in whom motor dysfunction and neuropathic pain are prevalent. However, therapy efficacy could be dependent on motor imagery ability, and a clear understanding of how motor imagery might be facilitated is currently lacking. Thus, the aim of the present study was to assess the immediate effects of interactive virtual feedback on motor imagery performance after SCI. METHODS: Nine individuals with a traumatic SCI participated in the experiment. Motor imagery tasks consisted of forward (i.e. simpler) and backward (i.e. more complex) walking while receiving interactive versus static virtual feedback. Motor imagery performance (vividness, effort and speed), neuropathic pain intensity and feasibility (immersion, distraction, side effects) were assessed. RESULTS: During interactive feedback trials, motor imagery vividness and speed were significantly higher and effort was significantly lower as compared static feedback trials. No change in neuropathic pain was observed. Adverse effects were minor, and immersion was reported to be good. CONCLUSIONS: This exploratory study showed that interactive virtual walking was feasible and facilitated motor imagery performance. The response to motor imagery interventions after SCI might be improved by using interactive virtual feedback. PMID- 26890099 TI - Neuroprotection and anti-seizure effects of levetiracetam in a rat model of penetrating ballistic-like brain injury. AB - PURPOSE: We assessed the therapeutic efficacy of FDA-approved anti-epileptic drug Levetiracetam (LEV) to reduce post-traumatic nonconvulsive seizure (NCS) activity and promote neurobehavioral recovery following 10% frontal penetrating ballistic like brain injury (PBBI) in male Sprague-Dawley rats. METHODS: Experiment 1 anti seizure study: 50 mg/kg LEV (25 mg/kg maintenance doses) was given twice daily for 3 days (LEV3D) following PBBI; outcome measures included seizures incidence, frequency, duration, and onset. Experiment 2 neuroprotection studies: 50 mg/kg LEV was given twice daily for either 3 (LEV3D) or 10 days (LEV10D) post-injury; outcome measures include motor (rotarod) and cognitive (water maze) functions. RESULTS: LEV3D treatment attenuated seizure activity with significant reductions in NCS incidence (54%), frequency, duration, and delayed latency to seizure onset compared to vehicle treatment. LEV3D treatment failed to improve cognitive or motor performance; however extending the dosing regimen through 10 days post injury afforded significant neuroprotective benefit. Animals treated with the extended LEV10D dosing regimen showed a twofold improvement in rotarod task latency to fall as well as significantly improved spatial learning performance (24%) in the MWM task. CONCLUSIONS: These findings support the dual anti- seizure and neuroprotective role of LEV, but more importantly identify the importance of an extended dosing protocol which was specific to the therapeutic targets studied. PMID- 26890100 TI - Vascular insufficiency, not inflammation, contributes to chronic gliosis in a rat CNS transplantation model. AB - PURPOSE: There is considerable variability in the extent and nature of the glial response to injury and neurodegeneration. Transplantation of fetal cortical tissue onto the brain of neonatal host rats or mice results in region-specific changes dependent on where the fetal tissue is placed. These changes include chronic astrocytic and microglial gliosis, oxidative stress, and altered metabolism of a number of proteins associated with the pathogenesis of Alzheimer's disease. Such changes are only observed in heterotopic (cortex-to midbrain) grafts and are not observed in homotopic cortex-to-cortex grafts. We investigated two possible triggers for the region-specific gliosis observed in our transplant model hypothesizing that either i) poor vascularization and lack of blood brain barrier integrity or ii) an inflammatory response initiated by the transplantation process, contributed to establishing chronic pathological changes. METHODS: We analyzed the time course of neovascularization, blood brain barrier permeability and inflammation using a combination of immunohistochemistry, enzyme-linked immunosorbant assay and Evan's blue dye extravasation techniques. RESULTS: Blood brain barrier permeability and altered neovascularization occurred prior to the onset of gliosis in heterotopic grafts. CONCLUSION: These data suggest that ischemic conditions and blood brain barrier damage can be a primary mechanism that initiates chronic gliosis and associated inflammatory changes in central nervous system tissue. PMID- 26890101 TI - Oxidative stress in the red blood cells of patients with primary open-angle glaucoma. AB - BACKGROUND: This study was designed to examine oxidative and antioxidative changes in the red blood cells (RBCs) of patients presenting with glaucomatous degeneration. METHODS: The experimental design was a case-control study of strictly selected patients who required antiglaucomatous surgery during primary open-angle glaucoma despite relatively regulated intraocular pressure (IOP) (POAG group, n = 30) and patients who underwent an operation for nonpathological cataracts (cataract group, n = 25). The activities of total superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the concentration of malondialdehyde (MDA), were measured. Glaucomatous damage was estimated from a transient pattern electroretinogram. RESULTS: Significant increases in GPX (p = 0.026) and CAT (p = 0.000) activity were noted in the RBCs of POAG patients compared to those of cataract patients. Although SOD was elevated in patients with POAG, the differences compared to cataract controls were not significant (p = 0.079). MDA concentrations were significantly increased in the glaucoma group compared to the cataract controls. CONCLUSION: An oxidative disorder primarily represented by catalase upregulation was observed during the course of glaucoma. PMID- 26890102 TI - Effect of encapsulation on plasminogen activator delivery to the microcirculation and its implications for bleeding. AB - BACKGROUND AND PURPOSE: It is known that encapsulation can alter the delivery of plasminogen activators by flow to accelerate fibrinolysis while other experimental studies suggest encapsulation may reduce the risk of hemorrhage with administration of the agent. The aim of this research is to resolve the effect of encapsulation on fibrinolysis and bleeding in the microcirculation. METHODS: An established rabbit model of fibrinolytic hemorrhage was utilized to explore the potential of encapsulation to limit bleeding. Equal dosages of free or microencapsulated streptokinase (MESK) were infused to initiate thrombolysis of small vessel clots while tracking blood loss. RESULTS: Compared to free streptokinase, significant improvements in bleeding were observed with MESK as demonstrated by (1) delayed onset of bleeding, (2) shortened duration, and (3) reduction in the volume of lost blood, consistent with less systemic fibrinogen degradation. CONCLUSIONS: Findings demonstrate that encapsulation of streptokinase can inhibit clot lysis in small vessels. Combined with prior work on accelerated thrombolysis, results suggest a time-based regimen for avoiding bleeding complications during thrombolytic therapy with encapsulated agent. PMID- 26890103 TI - Interspecies diversity of erythrocyte mechanical stability at various combinations in magnitude and duration of shear stress, and osmolality. AB - We hypothesized that the results of red blood cell mechanical stability test show interspecies differences. The comparative investigations were performed on blood samples obtained from rats, beagle dogs, pigs and healthy volunteers. Mechanical stress was applied in nine combinations: 30, 60 or 100 Pa shear stress for 100, 200 or 300 seconds. Generally, rat erythrocytes showed the highest capability of resistance. With the applied combinations of mechanical stress pig erythrocytes were the most sensitive. On human erythrocytes 60 Pa for 200 s was the minimum combination to result significant deformability deterioration. By increasing the magnitude and duration of the applied mechanical stress we experienced escalating deformability impairment in all species. 100 Pa shear stress for 300 seconds on human erythrocytes showed the largest deformability impairment. The mechanical stability test results were also dependent on osmolality. At hypoosmolar range (200 mOsmol/kg) the mechanical stress improved EI data mostly in rat and porcine blood. At higher osmolality (500 mOsmol/kg), the test did not show detectable difference, while in 250-300 mOsmol/kg range the differences were well observable. In summary, erythrocytes' capability of resistance against mechanical stress shows interspecies differences depending on the magnitude and duration of the applied stress, and on the osmolality. PMID- 26890104 TI - Effect of magnesium supplementation on blood rheology in NOS inhibition-induced hypertension model. AB - This study investigated the effects of magnesium on blood rheological properties and blood pressure in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension was induced by oral administration of the nonselective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg/day) for 6 weeks and systolic blood pressure was measured by the tail-cuff method. The groups receiving magnesium supplementation were fed with rat chow containing 0.8% magnesium oxide during the experiment. At the end of experiment, blood samples were obtained from abdominal aorta, using ether anesthesia. Plasma and erythrocyte magnesium levels were determined by the atomic absorption spectrometer. RBC deformability and aggregation were determined by rotational ektacytometry. Plasma fibrinogen concentration was evaluated by ELISA. Whole blood and plasma viscosities were determined by viscometer and intracellular free Ca++ level was measured by using spectroflurometric method. Blood pressure was elevated in hypertensive groups and suppressed by magnesium therapy. Plasma viscosity and RBC aggregation were found to be higher in hypertensive rats than control animals and these parameters significantly decreased in magnesium supplemented hypertensive animals. Other measurements were not different between experimental groups. These results confirm that blood pressure, plasma viscosity and RBC aggregation increased in NOS inhibition-induced hypertension model and oral magnesium supplementation improved these parameters. PMID- 26890105 TI - Hemorheological parameters better classify metabolic syndrome than novel cardiovascular risk factors and peripheral vascular disease marker. AB - The present study compares the association of Metabolic Syndrome (MetS) with hemorheological parameters, oxidative stress, inflammation and peripheral arterial disease markers. 100 participants were recruited and participants were divided into three groups on the basis of absence or presence of MetS and its components. Odds ratio for correctly predicting MetS was highest for erythrocyte aggregation followed by erythrocyte deformability. ROC curve analysis demonstrated that all the hemorheological components significantly classified MetS participants. Area Under Curve was higher for the hemorheological parameters (erythrocyte aggregation and erythrocyte deformability) than for the oxidative stress, inflammation and peripheral arterial disease markers. The possibilities of the hemorheological components to be identified as better cardiovascular risk markers due to their strong association with MetS cannot be precluded from the present findings. PMID- 26890106 TI - Erythrocyte deformability, plasma lipid peroxidation and plasma protein oxidation in a group of OSAS subjects. AB - Considering that obstructive sleep apnea syndrome (OSAS) is usually associated with endothelial dysfunction, atherosclerosis and cardiovascular disorders, our aim was to examine the erythrocyte deformability and the oxidative status in a group of OSAS subjects. We consecutively enrolled 48 subjects with OSAS defined after a 1-night cardiorespiratory sleep study, subsequently subdivided according to the apnea/hypopnea index (AHI) value in two subgroups: Low (L = 21 subjects with AHI<30) and High (H = 27 subjects with AHI>30). We evaluated the erythrocyte deformability, expressed as elongation index (EI) and the parameters of the oxidative status, such as lipid peroxidation (expressed as thiobarbituric acid reactive substances - TBARS) and protein oxidation (measured as carbonyl groups - PC). In the entire group and in the two subgroups of OSAS subjects we found a decreased erytrocyte deformability at all shear stresses, not correlated with the plasmatic oxidative stress nor with the polysomnographic parameters. Lipid peroxidation was increased in the whole group and in the H subgroup of OSAS while protein oxidation showed a different trend. As in OSAS the osmotic fragility and the metabolism of the red cells seem to be not impaired, the oxidative damage to the red cell membrane proteins might be responsible for the reduced erythrocyte deformability. This rheological alteration, in addition to the increase in whole blood and plasma viscosity and to the erythrocyte hyperaggregation, could influence the microcircolatory profile in OSAS subjects. PMID- 26890107 TI - Hypobaric hypoxia in 3000 m altitude leads to a significant decrease in circulating plasmacytoid dendritic cells in humans. AB - INTRODUCTION: Hypoxia is known to affect the immune system. It leads to an increase in pro-inflammatory cytokines such as interleukin-6 and influences the number of different inflammatory cells. This study investigates the effect of hypoxia on the number of different subsets of circulating human dendritic cells (DCs) as professional antigen-presenting cells. METHODS: The number of circulating DCs was determined via Fluorescence activated cell sorting analysis in peripheral blood of 17 healthy volunteers (age 35.9+/-2.6 years) in normoxia (baseline, BL), hypoxia (altitude 3000 m, alpine passive escalation), and again normoxia (follow-up, FU). RESULTS: Exposure to hypobaric hypoxia in high altitude, 3000 m, led to a significant decrease in the participants' oxygen saturation, and an increase in the breathing frequency whereas blood pressure and heart rate were not significantly altered. FACS analysis revealed a significant hypoxia induced decrease in circulating plasmacytoid (p) DCs compared to baseline levels (BL: 0.10 [0.08-0.18] % of white blood cell count (WBC), 3000 m: 0.03 [0.02-0.06] % WBC, p < 0.001). During follow up, again a significant reconstitution of circulating pDCs was observed (FU: 0.16+/-[0.11-0.26] % WBC, p = 0.0013). CONCLUSION: Hypobaric hypoxia caused by exposure to altitude results in a significant reduction in the number of circulating pDCs. PMID- 26890108 TI - Hemorheology in kidney transplantation: A role for cardiovascular risk? AB - Uremic patients undergoing dialysis (HD) present a cardiovascular risk of death 10-20 fold higher than general population, but also kidney transplantation keeps considerable cardiovascular burden.Hemorheologic profile alterations have been described in HD; comprehensive data on kidney transplant recipients (KT) are missing. Aim of our study is to characterize the hemorheological profile in KT, and to compare these data with HD and healthy volunteers (HV).We investigated 47 HV, 90 HD and 108 KT.We confirm hemorheological alterations in HD. KT, when compared to HD, normalizes many parameters: plasma viscosity, whole blood viscosity at 1-Hz and 200-Hz shear rate, erythrocyte aggregation index and yield stress. KT show a markedly lower erythrocyte deformability (ED). We found no differences among hemorheological parameters between the different classes of immunosuppressive drugs used.In conclusion, HD show various hemorheological defects; this could support the high incidence of cardiovascular complications. KT improves most hemorheological alterations; nevertheless, ED is reduced in KT, maintaining a detrimental injury at microcirculatory level and leading to the progression of fibrosis till to end-stage injury. Impaired ED in KT could also contribute to progression of interstitial fibrosis and tubular atrophy (IF/TA) in grafts. PMID- 26890109 TI - Impact of environment on Red Blood Cell ability to withstand mechanical stress. AB - Susceptibility of red blood cells (RBC) to hemolysis under mechanical stress is represented by RBC mechanical fragility (MF), with different types or intensities of stress potentially emphasizing different perturbations of RBC membranes. RBC membrane mechanics were shown to depend on cell environment, with many details not yet understood. Here, stress was applied to RBC using a bead mill with oscillation up to 50 Hz, over durations up to 50 minutes. MF profiles plot percent lysis upon stresses of progressive durations. Supplementing media with polyethylene glycol (PEG) which interacts with the cell membrane, but not Dextran which does not, resulted in higher resistance to hemolysis. Albumin, and to a lesser extent fibrinogen and globulins (at physiological concentrations), significantly increased cell ability to withstand mechanical stress versus with un-supplemented buffer solution and with PEG. This is partly due to changes in rheology, per tests done including (PEG) and Dextran, but is mostly due to cell protein interaction, noting the effect of pH on RBC MF with albumin but not with buffer. Presence of lipids reduced RBC resistance to potentially hemolytic stress with lypemic plasma effecting lower "protection" from induced hemolysis than essentially fatty-acid free plasma. This effect was less dependent on incubation than on fatty-acid presence during stressing. The reduced propensity for hemolysis afforded by plasma proteins also depended markedly on the speed of the bead, potentially reflecting changes from a predominantly Von Karman trail at lower frequencies to an increasingly disorganized turbulent wake at higher frequencies. PMID- 26890110 TI - Controlled reperfusion decreased reperfusion induced oxidative stress and evoked inflammatory response in experimental aortic-clamping animal model. AB - Revascularization after long term aortic ischaemia in vascular surgery induces reperfusion injury accompanied with oxidative stress and inflammatory responses. The hypothesis of this study was that the aortic occlusion followed by controlled reperfusion (CR) can reduce the ischaemia-reperfusion injury, the systemic and local inflammatory response induced by oxidative stress.Animal model was used. CONTROL GROUP: animals underwent a 4-hour infrarenal aortic occlusion followed by continuous reperfusion. Treated group: animals were treated with CR: after a 4 hour infrarenal aortic occlusion we made CR for 30 minutes with the crystalloid reperfusion solution (blood: crystalloid solution ratio 1:1) on pressure 60 Hgmm. Blood samples were collected different times. The developing oxidative stress was detected by the plasma levels of malondialdehyde, reduced glutathion, thiol groups and superoxide dismutase. The inflammatory response was measured by phorbol myristate acetate-induced leukocyte reactive oxygen species production and detection of change in myeloperoxidase levels. The animals were anaesthetized one week after terminating ligation and biopsy was taken from quadriceps muscle and large parenchymal organs.CR significantly reduced the postischaemic oxydative stress and inflammatory responses in early reperfusion period. Pathophysiological results: The rate of affected muscle fibers by degeneration was significantly higher in the untreated animal group. The infiltration of leukocytes in muscle and parenchymal tissues was significantly lower in the treatedgroup.CR can improve outcome after acute lower-limb ischaemia. The results confirm that CR might be also a potential therapeutic approach in vascular surgery against reperfusion injury in acute limb ischaemia. Supported by OTKA K108596. PMID- 26890111 TI - Remote ischemia preconditioning increases red blood cell deformability through red blood cell-nitric oxide synthase activation. AB - Remote ischemia preconditioning (rIPC), short cycles of ischemia (I) and reperfusion (R) of a region remote from the heart, protects against myocardial I/R injury. This effect is triggered by endothelial derived nitric oxide (NO) production. Red blood cells (RBC) are also capable of NO production and it is hypothesized that the beneficial effect of rIPC in terms of cardioprotection is strengthened by increased RBC dependent NO production and improved RBC function after rIPC maneuver. For this purpose, twenty male participants were subjected to four cycles of no-flow ischemia with subsequent reactive hyperemia within the forearm. Blood sampling and measurement of blood pressures and heart rate were carried out pre intervention, after each cycle and 15 min post intervention at both the non-treated and treated arm. These are the first results that show improved RBC deformability in the treated arm after rIPC cycles 1- 4 caused by significantly increased RBC-NO synthase activation. This in turn was associated to increased NO production in both arms after rIPC cycles 3 + 4. Also, systolic and diastolic blood pressures were decreased after rIPC. The findings lead to the conclusion that the cardioprotective effects associated with rIPC include improvement of the RBC-NOS/NO signaling in RBC. PMID- 26890112 TI - Azide-enolate 1,3-dipolar cycloaddition in the synthesis of novel triazole-based miconazole analogues as promising antifungal agents. AB - Seven miconazole analogs involving 1,4,5-tri and 1,5-disubstituted triazole moieties were synthesized by azide-enolate 1,3-dipolar cycloaddition. The antifungal activity of these compounds was evaluated in vitro against four filamentous fungi, including Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae, and Mucor hiemalis as well as three species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 4b, 4d and 7b can be considered as drug candidates for future complementary biological studies due to their good/excellent antifungal activities. PMID- 26890113 TI - Tricyclic pyrazoles. Part 8. Synthesis, biological evaluation and modelling of tricyclic pyrazole carboxamides as potential CB2 receptor ligands with antagonist/inverse agonist properties. AB - Previous studies have investigated the relevance and structure-activity relationships (SARs) of pyrazole derivatives in relation with cannabinoid receptors, and the series of tricyclic 1,4-dihydroindeno[1,2-c]pyrazoles emerged as potent CB2 receptor ligands. In the present study, novel 1,4-dihydroindeno[1,2 c]pyrazole and 1H-benzo[g]indazole carboxamides containing a cyclopropyl or a cyclohexyl substituent were designed and synthesized to evaluate the influence of these structural modifications towards CB1 and CB2 receptor affinities. Among these derivatives, compound 15 (6-cyclopropyl-1-(2,4-dichlorophenyl)-N-(adamantan 1-yl)-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide) showed the highest CB2 receptor affinity (Ki = 4 nM) and remarkable selectivity (KiCB1/KiCB2 = 2232), whereas a similar affinity, within the nM range, was seen for the fenchyl derivative (compound 10: Ki = 6 nM), for the bornyl analogue (compound 14: Ki = 38 nM) and, to a lesser extent, for the aminopiperidine derivative (compound 6: Ki = 69 nM). Compounds 10 and 14 were also highly selective for the CB2 receptor (KiCB1/KiCB2 > 1000), whereas compound 6 was relatively selective (KiCB1/KiCB2 = 27). The four compounds were also subjected to GTPgammaS binding analysis showing antagonist/inverse agonist properties (IC50 for compound 14 = 27 nM, for 15 = 51 nM, for 10 = 80 nM and for 6 = 294 nM), and this activity was confirmed for the three more active compounds in a CB2 receptor-specific in vitro bioassay consisting in the quantification of prostaglandin E2 release by LPS-stimulated BV2 cells, in the presence and absence of WIN55,212-2 and/or the investigated compounds. Modelling studies were also conducted with the four compounds, which conformed with the structural requirements stated for the binding of antagonist compounds to the human CB2 receptor. PMID- 26890115 TI - Design, synthesis, pharmacological evaluation, and docking study of new acridone based 1,2,4-oxadiazoles as potential anticonvulsant agents. AB - A number of acridone-based oxadiazoles 11a-n have been synthesized and evaluated for their anticonvulsant activity against pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice. Also, their neurotoxicity was evaluated by the rotarod test. Most of the compounds exhibited better anticonvulsant activity and higher safety respect to the standard drug, phenobarbital. Among the tested derivatives, compounds 11l with ED50 value of 2.08 mg/kg was the most potent compound in the PTZ test. The anticonvulsant effect of compound 11l was blocked by flumazenil, suggesting the involvement of benzodiazepine (BZD) receptors in the anticonvulsant activity of prototype compound 11l. Also, docking study of compound 11l in the BZD-binding site of GABAA receptor confirms possible binding of compound 11l with BZD receptors. PMID- 26890114 TI - Design, synthesis and biological evaluation of bisthiazole-based trifluoromethyl ketone derivatives as potent HDAC inhibitors with improved cellular efficacy. AB - Histone deacetylases (HDACs) are a class of epigenetic modulators with complex functions in histone post-translational modifications and are well known targets for antineoplastic drugs. We have previously developed a series of bisthiazole based hydroxamic acids as novel potent HDAC inhibitors. In the present work, a new series of bisthiazole-based compounds with different zinc binding groups (ZBGs) have been designed and synthesized. Among them is compound 7, containing a trifluoromethyl ketone as the ZBG, which displays potent inhibitory activity towards human HDACs and improved antiproliferative activity in several cancer cell lines. PMID- 26890116 TI - Biphenyl-4-yl-acrylohydroxamic acids: Identification of a novel indolyl substituted HDAC inhibitor with antitumor activity. AB - Modification of the cap group of biphenylacrylohydroxamic acid-based HDAC inhibitors led to the identification of a new derivative (3) characterized by an indolyl-substituted 4-phenylcinnamic skeleton. Molecular docking was used to predict the optimal conformation in the class I HDACs active site. Compound 3 showed HDAC inhibitory activity and antiproliferative activity against a panel of tumor cell lines, in the low MUM range. The compound was further tested in vitro for acetylation of histone H4 and other non-histone proteins, and in vivo in a colon carcinoma model, showing significant proapoptotic and antitumor activities. PMID- 26890117 TI - Synthesis and antitumor evaluation of trimethoxyanilides based on 4(3H) quinazolinone scaffolds. AB - A novel series of 2-[(3-substituted-4(3H)-quinazolin-2-yl)thio]-N-(3,4,5 trimethoxyphenyl)acetamide (15-21) and 3-[(3-substituted-4(3H)-quinazolin-2 yl)thio])-N-(3,4,5-trimethoxyphenyl)propanamide (23-29) were designed, prepared and estimated for their anticancer activity in a solo dose 10 MUM of the test compounds in the NCI 57 cell lines panel assay. Compounds 20, 23, 26, 27 and 28 revealed extensive-spectrum antitumor efficiency to numerous cell lines that belong to various tumor subpanels, while compounds 15, 16 and 19 possessed perceptive activity toward A498 and UO-31 renal cancer cell lines, and compound 17 showed selective effectiveness against NSC lung cancer NCI-H522 cell line. Additionally, compound 18 showed advanced activity against SR leukemia cell line, NSC lung cancer HOP-92 and renal cancer UO-31 cell lines. PMID- 26890118 TI - Discovery of antitumor anthra[2,3-b]furan-3-carboxamides: Optimization of synthesis and evaluation of antitumor properties. AB - Anthraquinones and their analogues, in particular heteroarene-fused anthracendiones, are prospective scaffolds for new compounds with improved antitumor characteristics. We herein report the use of a 'scaffold hopping' approach for the replacement of the core structure in the previously discovered hit compound naphtho[2,3-f]indole-5,10-dione 2 with an alternative anthra[2,3 b]furan-5,10-dione scaffold. Among 13 newly synthesized derivatives the majority of 4,11-dihydroxy-2-methyl-5,10-dioxoanthra[2,3-b]furan-3-carboxamides demonstrated a high antiproliferative potency against a panel of wild type and drug resistant tumor cell lines, a property superior over the reference drug doxorubicin or lead naphtho[2,3-f]indole-5,10-dione 2. At low micromolar concentrations the selected derivative of (R)-3-aminopyrrolidine 3c and its stereoisomer (S)-3-aminopyrrolidine 3d caused an apoptotic cell death preceded by an arrest in the G2/M phase. Studies of intracellular targets showed that 3c and 3d formed stable intercalative complexes with the duplex DNA as determined by spectral analysis and molecular docking. Both 3c and 3d attenuated topoisomerase 1 and 2 mediated unwinding of the supercoiled DNA via a mechanism different from conventional DNA-enzyme tertiary complex formation. Furthermore, 3d decreased the activity of selected human protein kinases in vitro, indicating multiple targeting by the new chemotype. Finally, 3d demonstrated an antitumor activity in a model of murine intraperitoneally transplanted P388 leukemia, achieving the increase of animal life span up to 262% at tolerable doses. Altogether, the 'scaffold hopping' demonstrated its productivity for obtaining new perspective antitumor drug candidates. PMID- 26890120 TI - Synthesis and anti-cancer activity evaluation of 5-(2-carboxyethenyl)-isatin derivatives. AB - A series of novel di- or trisubstituted isatin derivatives were designed and synthesized in 5-6 steps in 25-45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC-MS. The anticancer activity of the fourty-three new isatin derivatives against human T lymphocyte cells Jurkat was evaluated by MTT assay in vitro. SAR study suggested that the combination of 1 benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhanced their cytotoxic activity. Among them, compound 2h was shown to have a significant cytotoxic activity with an IC50 value of 0.03 MUM, more than 330-fold higher than that of it's mother molecule isatin. Investigation of the cell morphology changes and annexin-V/PI staining study demonstrated that compound 2h inhibited the proliferation of Jurkat cells by inducing apoptosis. Since compound 2h induced the dissipation of mitochondrial membrane potential and the activation of caspase 3, it was obvious that compound 2h inhibited the proliferation of Jurkat cells through the mitochondrial apoptotic pathway. Other than this, compound 2h exerted inhibition effect to many other tumor cells and only showed weak cytotoxic to human normal cells suggesting that compound 2h possessed a broad range of anticancer spectrum and high safety to normal cells. PMID- 26890121 TI - Critical kinetic control of non-stoichiometric intermediate phase transformation for efficient perovskite solar cells. AB - Organometal trihalide perovskites (OTP) have attracted significant attention as a low-cost and high-efficiency solar cell material. Due to the strong coordination between lead iodide (PbI2) and dimethyl sulfoxide (DMSO) solvent, a non stoichiometric intermediate phase of MA2Pb3I8(DMSO)2 (MA = CH3NH3(+)) usually forms in the one-step deposition method that plays a critical role in attaining high power conversion efficiency. However, the kinetic understanding of how the non-stoichiometric intermediate phase transforms during thermal annealing is currently absent. In this work, we investigated such a phase transformation and provided a clear picture of three phase transition pathways as a function of annealing conditions. The interdiffusion of MAI and DMSO varies strongly with the annealing temperature and time, thus determining the final film composition and morphology. A surprising finding reveals that the best performing cells contain ~18% of the non-stoichiometric intermediate phase, instead of pure phase OTP. The presence of such an intermediate phase enables smooth surface morphology and enhances the charge carrier lifetime. Our results highlight the importance of the intermediate phase growth kinetics that could lead to large-scale production of efficient solution processed perovskite solar cells. PMID- 26890119 TI - Small molecule glycoconjugates with anticancer activity. AB - Glycoconjugates are combinations of sugar moieties with organic compounds. Due to their biological resemblance, such structures often have properties that are desirable for drugs. In this study we designed and synthesised several glycoconjugates from small molecular quinolines and substituted gluco- and galactopyranosyl amines. Although the parent quinoline compounds were inactive in affordable concentrations, the glycoconjugates that were obtained appeared to be cytotoxic against cancer cells at the micromolar level. When combined with copper ions, their activity increased even further. Their mechanism of action is connected to the formation of reactive oxygen species and the intercalation of DNA. PMID- 26890122 TI - Behcet's: A Disease or a Syndrome? Answer from an Expression Profiling Study. AB - Behcet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behcet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" ? "OB vs C" ? "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behcet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis. PMID- 26890123 TI - Membrane Potential Dynamics of Spontaneous and Visually Evoked Gamma Activity in V1 of Awake Mice. AB - Cortical gamma activity (30-80 Hz) is believed to play important functions in neural computation and arises from the interplay of parvalbumin-expressing interneurons (PV) and pyramidal cells (PYRs). However, the subthreshold dynamics underlying its emergence in the cortex of awake animals remain unclear. Here, we characterized the intracellular dynamics of PVs and PYRs during spontaneous and visually evoked gamma activity in layers 2/3 of V1 of awake mice using targeted patch-clamp recordings and synchronous local field potentials (LFPs). Strong gamma activity patterned in short bouts (one to three cycles), occurred when PVs and PYRs were depolarizing and entrained their membrane potential dynamics regardless of the presence of visual stimulation. PV firing phase locked unconditionally to gamma activity. However, PYRs only phase locked to visually evoked gamma bouts. Taken together, our results indicate that gamma activity corresponds to short pulses of correlated background synaptic activity synchronizing the output of cortical neurons depending on external sensory drive. PMID- 26890124 TI - Vocalisation Repertoire of Female Bluefin Gurnard (Chelidonichthys kumu) in Captivity: Sound Structure, Context and Vocal Activity. AB - Fish vocalisation is often a major component of underwater soundscapes. Therefore, interpretation of these soundscapes requires an understanding of the vocalisation characteristics of common soniferous fish species. This study of captive female bluefin gurnard, Chelidonichthys kumu, aims to formally characterise their vocalisation sounds and daily pattern of sound production. Four types of sound were produced and characterised, twice as many as previously reported in this species. These sounds fit two aural categories; grunt and growl, the mean peak frequencies for which ranged between 129 to 215 Hz. This species vocalized throughout the 24 hour period at an average rate of (18.5 +/- 2.0 sounds fish-1 h-1) with an increase in vocalization rate at dawn and dusk. Competitive feeding did not elevate vocalisation as has been found in other gurnard species. Bluefin gurnard are common in coastal waters of New Zealand, Australia and Japan and, given their vocalization rate, are likely to be significant contributors to ambient underwater soundscape in these areas. PMID- 26890125 TI - A Comparison of Pig Farmers' and Veterinarians' Perceptions and Intentions to Reduce Antimicrobial Usage in Six European Countries. AB - Antimicrobial (AM) resistance is an increasing problem in human and veterinary medicine. To manage this problem, the usage of AM should be reduced in pig farming, as well as in other areas. It is important to investigate the factors that influence both pig farmers' and veterinarians' intentions to reduce AM usage, which is a prerequisite for developing intervention measures. We conducted a mail survey among pig farmers (N = 1,294) and an online survey among veterinarians (N = 334) in Belgium, Denmark, France, Germany, Sweden and Switzerland. The farmers' survey assessed the perceived risks and benefits of and need for AM usage; the intention to reduce AM usage; farmers' efficacy (i.e. perception of their ability to reduce AM usage); support from their veterinarian; and the future reduction potential of AM usage. Additionally, self-reported reduction behaviours, the perceived farmers' barriers to reduce AM usage and relationships with farmers were assessed in the veterinarians' survey. The results showed that farmers and veterinarians had similar perceptions of the risks and benefits of AM usage. Veterinarians appeared to be more optimistic than pig farmers about reducing AM usage in pig farming. Farmers believed that their efficacy over AM reduction was relatively high. Farmers' intention to reduce AM usage and veterinarians' self-reported reduction behaviours were mainly associated with factors concerning the feasibility of reducing AM usage. To promote prudent AM usage, pig farmers should learn and experience how to reduce usage by applying alternative measures, whereas veterinarians should strengthen their advisory role and competencies to support and educate farmers. PMID- 26890126 TI - Genomic Features: Impact on Pathogenesis and Treatment of Chronic Lymphocytic Leukemia. AB - Genomic markers are among the strongest prognostic factors in chronic lymphocytic leukemia (CLL). Chromosomal aberrations, IGHV and TP53 mutation status are well established and essential to discriminate between a more indolent course of disease and a high-risk CLL, which requires an alternative treatment regimen. In addition, a variety of gene mutations with unclear prognostic value have been identified: SF3B1, ATM, and BIRC3 may describe CLL with adverse outcome, whereas NOTCH1 is predictive for resistance against CD20 antibodies. Integration of novel drivers into a small set of key pathways forms the basis for future pathogenetic and therapeutic implications. PMID- 26890127 TI - Prevalence of very low birthweight, malformation, and low Apgar score among newborns in Brazil according to maternal urban or rural residence at birth. AB - AIM: Adverse birth outcomes are a major public health issue in rural areas, where several environmental risk factors, including pesticides, may endanger the health of women of reproductive age. We investigated the prevalence of selected birth outcomes among newborns from mothers living in urban and rural areas of a Brazilian municipality. METHODS: Information about all live births that occurred between 2004 and 2006 in the Municipality of Nova Friburgo, Brazil, was retrieved from the Live Birth Information System. Newborns were classified as rural or urban, according to the mother's residence address. RESULTS: Newborns from rural areas had a higher prevalence of very low-birthweight, low Apgar score, and malformation. On Poisson regression with adjustment for several confounders, rural offspring were more likely to have the aforementioned outcomes. CONCLUSIONS: Women in rural areas are at higher risk of giving birth to an infant with very low-birthweight, low 5-min Apgar score and malformations detectable at birth, regardless of socioeconomic and gestational conditions. PMID- 26890130 TI - Why Are Women Underrepresented in STEM Fields? AB - Women are still underrepresented in the so-called "hard" fields of science, technology, engineering, and mathematics (STEM). In this Guest Editorial, H. Nimmesgern, Chairwoman of the Arbeitskreis Chancengleichheit in der Chemie (AKCC), a working group of the German Chemical Society (GDCh), describes the challenges women in science face and organizations that have been set up to help them in their research careers. PMID- 26890128 TI - Economic evaluation of vaccines in Canada: A systematic review. AB - BACKGROUND: Economic evaluations should form part of the basis for public health decision making on new vaccine programs. While Canada's national immunization advisory committee does not systematically include economic evaluations in immunization decision making, there is increasing interest in adopting them. We therefore sought to examine the extent and quality of economic evaluations of vaccines in Canada. OBJECTIVE: We conducted a systematic review of economic evaluations of vaccines in Canada to determine and summarize: comprehensiveness across jurisdictions, studied vaccines, funding sources, study designs, research quality, and changes over time. METHODS: Searches in multiple databases were conducted using the terms "vaccine," "economics" and "Canada." Descriptive data from eligible manuscripts was abstracted and three authors independently evaluated manuscript quality using a 7-point Likert-type scale scoring tool based on criteria from the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). RESULTS: 42/175 articles met the search criteria. Of these, Canada-wide studies were most common (25/42), while provincial studies largely focused on the three populous provinces of Ontario, Quebec and British Columbia. The most common funding source was industry (17/42), followed by government (7/42). 38 studies used mathematical models estimating expected economic benefit while 4 studies examined post-hoc data on established programs. Studies covered 10 diseases, with 28/42 addressing pediatric vaccines. Many studies considered cost-utility (22/42) and the majority of these studies reported favorable economic results (16/22). The mean quality score was 5.9/7 and was consistent over publication date, funding sources, and disease areas. CONCLUSIONS: We observed diverse approaches to evaluate vaccine economics in Canada. Given the increased complexity of economic studies evaluating vaccines and the impact of results on public health practice, Canada needs improved, transparent and consistent processes to review and assess the findings of the economic evaluations of vaccines. PMID- 26890129 TI - Predictors of Delayed Healthcare Seeking Among American Muslim Women. AB - BACKGROUND: Delayed care seeking is associated with adverse health outcomes. For Muslim women, delayed care seeking might include religion-related motivations, such as a preference for female clinicians, concerns about preserving modesty, and fatalistic beliefs. Our study assesses associations between religion-related factors and delayed care seeking due to a perceived lack of female clinicians. MATERIALS AND METHODS: Surveys were distributed to Muslim women attending mosque and community events in Chicago. Survey items included measures of religiosity, religious fatalism, discrimination, modesty, and alternative medicine utilization and worship practices. The outcome measure asked for levels of agreement to the statement "I have delayed seeking medical care when no woman doctor is available to see me." RESULTS: Two hundred fifty-four women completed the survey with nearly equal numbers of African Americans (26%), Arab Americans (33%), and South Asians (33%). Fifty-three percent reported delays in care seeking due to a perceived lack of female clinicians. In multivariate analysis adjusting for sociodemographic factors, higher religiosity (odds ratio [OR] = 5.2, p < 0.01) and modesty levels (OR = 1.4, p < 0.001) were positively associated with delayed care seeking. Having lived in the United States for >20 years (OR = 0.22, p < 0.05) was negatively associated with delayed care seeking. CONCLUSION: Many American Muslim women reported delays in care seeking due to a perceived lack of female clinicians. Women with higher levels of modesty and self-rated religiosity had higher odds of delaying care. Women who had lived in the United States for longer durations had lower odds of delaying care. Our research highlights the need for gender-concordant providers and culturally sensitive care for American Muslims. PMID- 26890131 TI - Comparisons of body sizes at sexual maturity and at sex change in the parrotfishes of Hawaii: input needed for management regulations and stock assessments. AB - First estimates of sex allocation patterns and body size-at-sexual maturity and at protogynous sex change are presented for the five major (including one endemic) species of parrotfishes of Hawaii. Median body size at initial maturation as a female (LM50) and at protogynous sex change from adult female to adult male (LDelta50) varied greatly among the five species. Estimates of LM50 were about 14, 17, 24, 34 and 35 cm fork length (LF) in palenose Scarus psittacus, Pacific bullethead Chlorurus spilurus, stareye Calotomus carolinus, spectacled Chlorurus perspicillatus and redlip parrotfish Scarus rubroviolaceus. Values of LDelta50 were c. 23, 27, 37, 46 and 47 cm LF in the respective species. Length at female maturation was proportional to maximum body size (Lmax) of the respective species, ranging from 50 to 72% and averaging 62% of Lmax across species. LDelta50 was also proportional to Lmax, ranging from 82 to 97% and averaging 92%. Males of both pairs of Scarus and Chlorurus spp. reported here are diandric. Only one of the five major species (C. carolinus) is functionally monandric, with either all or nearly all males secondarily derived from adult females. The broadly differing absolute body sizes at sexual maturation and at sex change among the five species have important implications for improving regulatory size limits for parrotfishes in the State of Hawaii, where parrotfish species have historically been managed based on a single minimum size limit of 30.5 cm LF. This study provides a model demonstration of why catch data for parrotfishes, and other size-structured reef-fish populations, should be recorded either by species or by functional size-groups of species that allow setting more meaningful minimum size limits. PMID- 26890132 TI - Erratum. PMID- 26890134 TI - Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease. AB - Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease. PMID- 26890136 TI - Extracellular ATP and P2X7 receptor exert context-specific immunogenic effects after immunogenic cancer cell death. PMID- 26890135 TI - Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease. AB - Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic fatty liver disease), insulin resistance and the metabolic syndrome. Recently, caspase-2 was linked to lipoapoptosis, so we hypothesized that caspase-2 might be a critical determinant of metabolic syndrome pathogenesis. Caspase-2-deficient and wild-type mice were fed a Western diet (high-fat diet, enriched with saturated fatty acids and 0.2% cholesterol, supplemented with fructose and glucose in the drinking water) for 16 weeks. Metabolic and hepatic outcomes were evaluated. In vitro studies assessed the role of caspase-2 in adipose tissue proliferative properties and susceptibility for lipoapoptosis. Caspase-2-deficient mice fed a Western diet were protected from abdominal fat deposition, diabetes mellitus, dyslipidemia and hepatic steatosis. Adipose tissue in caspase-2-deficient mice was more proliferative, upregulated mitochondrial uncoupling proteins consistent with browning, and was resistant to cell hypertrophy and cell death. The liver was protected from steatohepatitis through a decrease in circulating fatty acids and more efficient hepatic fat metabolism, and from fibrosis as a consequence of reduced fibrogenic stimuli from fewer lipotoxic hepatocytes. Caspase-2 deficiency protected mice from diet induced obesity, metabolic syndrome and nonalcoholic fatty liver disease. Further studies are necessary to assess caspase-2 as a therapeutic target for those conditions. PMID- 26890137 TI - The anticancer effect of chaetocin is enhanced by inhibition of autophagy. AB - Chaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer. PMID- 26890138 TI - AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-beta signal. AB - Dedifferentiation and degeneration of chondrocytes critically influences the efficiency of cartilage repair. One of the causes is the defect of transforming growth factor (TGF)-beta signaling that promotes chondrogenic differentiation and degeneration. In the present study, we found that aminoacyl-tRNA synthetase interacting multifunctional protein 1 (AIMP1) negatively regulates TGF-beta signaling via interactions with Smad2 and Smad3 in immunoprecipitation assay and luciferase assay. In addition, we observed that the AIMP1 expression level was significantly increased in osteoarthritis (OA) patient-derived degenerated chondrocytes compared with healthy control. So, we hypothesized that downregulation of AIMP1 using small-interfering RNA (siRNA) technology in dedifferentiated (collected at passage #6) and degenerated (obtained from OA affected areas) chondrocytes could lead to recover TGF-beta signaling in both chondrocytes. Indeed, AIMP1 downregulation restored TGF-beta signaling by promoting phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics in both dedifferentiated and degenerated chondrocytes. Additionally, implantation analyses using in vivo mouse model clearly showed that AIMP1 downregulation resulted in the increased chondrogenic potential as well as the enhanced cartilage tissue formation in both dedifferentiated and degenerated chondrocytes. Histological analyses clarified that AIMP1 downregulation increased expression levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken together, these data indicate that AIMP1 downregulation using siRNA is a novel tool to restore TGF-beta signaling and thereby increases the chondrogenic potential of dedifferentiated/degenerated chondrocytes, which could be further developed as a therapeutic siRNA to treat OA. PMID- 26890139 TI - Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer's disease mouse model. AB - Altered neuronal excitability is emerging as an important feature in Alzheimer's disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca(2+)]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1 dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8 tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain. PMID- 26890140 TI - Angiopoietin 2 induces astrocyte apoptosis via alphavbeta5-integrin signaling in diabetic retinopathy. AB - The vascular leakage in diabetic retinopathy leads to macular edema and vision loss. Although astrocyte play an important role in regulating blood-brain barrier integrity in the brain, the precise role of astrocyte in blood-retinal barrier was yet to be elucidated. This study aimed to investigate the role of angiopoietin 2 (Ang2) in astrocyte loss and vascular leakage in the early streptozotocin-induced diabetic retinopathy. We demonstrated that vascular leakage occurred with astrocyte loss in early diabetic mice retina as Ang2 increased. The astrocyte loss and vascular leakage were inhibited by intravitreal injection of Ang2-neutralizing antibody. In vitro, Ang2 aggravated high glucose induced astrocyte apoptosis via GSK-3beta activation. Ang2 directly bound to alphavbeta5 integrin, which was abundant in astrocyte, and the blockade of alphavbeta5 integrin, in vitro, effectively attenuated Ang2-induced astrocyte apoptosis. In vivo, intravitreal injection of anti-alphavbeta5-integrin antibody inhibited astrocyte loss in early diabetic retinopathy. Taken together, Ang2 induced astrocyte apoptosis under high glucose via alphavbeta5-integrin/GSK 3beta/beta-catenin pathway. Therefore, we suggest that Ang2/integrin signaling could be a potential therapeutic target to prevent the vascular leakage by astrocyte loss in early diabetic retinopathy. PMID- 26890141 TI - The transcriptional coactivator PGC1alpha protects against hyperthermic stress via cooperation with the heat shock factor HSF1. AB - Heat shock proteins (HSPs) are required for the clearance of damaged and aggregated proteins and have important roles in protein homeostasis. It has been shown that the heat shock transcription factor, HSF1, orchestrates the transcriptional induction of these stress-regulated chaperones; however, the coregulatory factors responsible for the enhancement of HSF1 function on these target genes have not been fully elucidated. Here, we demonstrate that the cold inducible coactivator, PGC1alpha, also known for its role as a regulator of mitochondrial and peroxisomal biogenesis, thermogenesis and cytoprotection from oxidative stress, regulates the expression of HSPs in vitro and in vivo and modulates heat tolerance. Mechanistically, we show that PGC1alpha physically interacts with HSF1 on HSP promoters and that cells and mice lacking PGC1alpha have decreased HSPs levels and are more sensitive to thermal challenges. Taken together, our findings suggest that PGC1alpha protects against hyperthermia by cooperating with HSF1 in the induction of a transcriptional program devoted to the cellular protection from thermal insults. PMID- 26890143 TI - Role of apoptosis-related miRNAs in resveratrol-induced breast cancer cell death. AB - Breast cancer is the most frequently diagnosed cancer in women, and one of the leading causes of cancer-related deaths worldwide. Recent evidences indicate that dietary agents such as resveratrol may inhibit cancer progression through modulation of microRNAs (miRNAs). We demonstrate that resveratrol regulates apoptotic and cell cycle machinery in breast cancer cells by modulating key tumor suppressive miRNAs including miR-125b-5p, miR-200c-3p, miR-409-3p, miR-122-5p and miR-542-3p. Resveratrol-mediated miRNA modulation regulates key anti-apoptotic and cell cycle proteins including Bcl-2, X-linked inhibitor of apoptosis protein and CDKs, which are critical for its activity. Modulating miRNAs with mimics or inhibitors further validated a key role for miR-542-3p in MCF-7 and miR-122-5p in MDA-MB-231 breast cancer cell death in response to resveratrol. In conclusion, this study reveals novel miRNAs modulated by resveratrol that have a key role in breast cancer cell death. PMID- 26890142 TI - The anti-apoptotic Bcl-2 family protein A1/Bfl-1 regulates neutrophil survival and homeostasis and is controlled via PI3K and JAK/STAT signaling. AB - Neutrophil granulocytes are innate effector cells of the first line of defense against pyogenic bacteria. Neutrophil lifespan is short, is prolonged by pro inflammatory stimuli, controls functionality of the cells and can determine tissue damage. Experimental analysis of primary neutrophils is difficult because of their short lifespan and lack of possibilities of genetic manipulation. The Hoxb8 system of neutrophil differentiation from immortalized progenitor cells offers the advantage of unlimited production of neutrophils in vitro as well as easy genetic modification. We here use this system to analyze the role of the poorly characterized anti-apoptotic B-cell lymphoma protein 2 (Bcl-2) family member A1/Bfl-1 (Bcl-2-related protein A1) for survival and homeostasis of neutrophils and of neutrophil progenitors. Low constitutive mRNA and protein expression of A1 was detected, while A1 was transiently upregulated early during differentiation. Pro-inflammatory stimuli caused strong, mainly transcriptional, A1 upregulation, in contrast to posttranscriptional regulation of Mcl-1 (induced myeloid leukemia cell differentiation protein). Inhibitor studies showed that phosphoinositide-3 kinase (PI3K)/Akt and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) is required for A1 expression and survival of progenitors and mature neutrophils. ShRNA-mediated constitutive A1 knockdown (KD) impaired maintenance of progenitors. ShRNA experiments further showed that A1 was required early during neutrophil differentiation as well as in mature neutrophils upon pro-inflammatory stimulation. Our data further indicate differential regulation of the two anti-apoptotic proteins A1 and Mcl-1. Relevant findings were confirmed in primary human neutrophils. Our data indicate that A1, in addition to the well-established Mcl-1, substantially contributes to neutrophil survival and homeostasis. A1 may thus be a promising target for anti-inflammatory therapy. PMID- 26890147 TI - From gene discovery to precision intervention in epilepsy: almost the end of the beginning. PMID- 26890144 TI - Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation. AB - Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by a dramatic appearance of premature aging. HGPS is due to a single-base substitution in exon 11 of the LMNA gene (c.1824C>T) leading to the production of a toxic form of the prelamin A protein called progerin. Because farnesylation process had been shown to control progerin toxicity, in this study we have developed a screening method permitting to identify new pharmacological inhibitors of farnesylation. For this, we have used the unique potential of pluripotent stem cells to have access to an unlimited and relevant biological resource and test 21,608 small molecules. This study identified several compounds, called monoaminopyrimidines, which target two key enzymes of the farnesylation process, farnesyl pyrophosphate synthase and farnesyl transferase, and rescue in vitro phenotypes associated with HGPS. Our results opens up new therapeutic possibilities for the treatment of HGPS by identifying a new family of protein farnesylation inhibitors, and which may also be applicable to cancers and diseases associated with mutations that involve farnesylated proteins. PMID- 26890145 TI - Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo. AB - Cucurbitacin-I (Cu-I, also known as Elatericin B or JSI-124) is developed to inhibit constitutive and abnormal activation of STAT3 in many cancers, demonstrating a potent anticancer activity by targeting disruption of STAT3 function. Here, we for the first time systematically studied the underlying molecular mechanisms of Cu-I-induced gastric cancer cell death both in vitro and in vivo. In our study, we show that Cu-I markedly inhibits gastric cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis at low nanomolar concentrations via a STAT3-independent mechanism. Notably, Cu-I significantly decreases intracellular GSH/GSSG ratio by inhibiting NRF2 pathway to break cellular redox homeostasis, and subsequently induces the expression of GADD45alpha in a p53-independent manner, and activates JNK/p38 MAPK signaling. Interestingly, Cu-I-induced GADD45alpha and JNK/p38 MAPK signaling form a positive feedback loop and can be reciprocally regulated by each other. Therefore, the present study provides new insights into the mechanisms of antitumor effects of Cu-I, supporting Cu-I as an attractive therapeutic drug in gastric cancer by modulating the redox balance. PMID- 26890146 TI - Loss of Merlin/NF2 protects pancreatic beta-cells from apoptosis by inhibiting LATS2. PMID- 26890148 TI - Spatial patterns of off-the-system traffic crashes in Miami-Dade County, Florida, during 2005-2010. AB - OBJECTIVE: The objective of this study is to analyze the spatial distribution of the vehicles involved in crashes in Miami-Dade County. In addition, we analyzed the role of time of day, day of the week, seasonality, drivers' age in the distribution of traffic crashes. METHOD: Off-the-system crash data acquired from the Florida Department of Transportation during 2005-2010 were divided into subcategories according to the risk factors age, time of day, day of the week, and travel season. Various spatial statistics methods, including nearest neighbor analysis, Getis-Ord hot spot analysis, and kernel density analysis revealed substantial spatial variations, depending on the subcategory in question. RESULTS: Downtown Miami and South Beach showed up consistently as hotspots of traffic crashes in all subcategories except fatal crashes. However, fatal crashes were concentrated in residential areas in inland areas. CONCLUSION: This understanding of patterns can help the county target high-risk areas and help to reduce crash fatalities to create a safer environment for motorists and pedestrians. PMID- 26890149 TI - Nanoparticles of gadolinium-incorporated Prussian blue with PEG coating as an effective oral MRI contrast agent for gastrointestinal tract imaging. AB - Biocompatible nanoparticles of gadolinium-incorporated Prussian blue with the empirical formula K(0.94)Gd(0.02)Fe[Fe(CN)6] exhibit extremely high stability against the release of Gd(3+) and CN(-) ions under the acidic conditions similar to stomach juice. The high r1 relaxivity, low cytotoxicity and the ability of such nanoparticles to penetrate the cell membrane suggest that this coordination polymer structural platform offers a unique opportunity for developing the next generation of T1-weighted oral cellular MRI probes for the early detection of tumors in the gastrointestinal tract. PMID- 26890151 TI - Calorimetric and spectroscopic studies on solvation energetics for H2 storage in the CO2/HCOOH system. AB - Solvents playing a crucial role in many chemical reactions and additives can be used to shift the reaction equilibrium. Herein we study the enthalpy of mixing for selected solvents (aqueous, organic) and basic additives (amines, aqueous KOH) when mixed with formic acid with the aim to optimize hydrogen storage/delivery in the CO2/HCOOH system. Formic acid, resulting from carbon dioxide hydrogenation, reaches highest yields when effectively "removed" from the reaction equilibrium. In terms of energy efficiency, any heat released during CO2 hydrogenation has to be reused in the reverse reaction, during the production of hydrogen. In any scenario, the usage of basic chemicals, non-innocent solvents, causes higher energy release in CO2 hydrogenation, which has to be reused in the hydrogen delivery process. Therefore, the enthalpy of mixing is a valuable parameter for designing hydrogen storage devices since it allows the estimation of energy balance for the CO2 hydrogenation/H2 liberation cycle. The highest formic acid concentrations in direct catalytic CO2 hydrogenation under acidic conditions were reached in DMSO. DMSO exhibits considerably stronger interactions with formic acid compared to water as was observed in calorimetric measurements. This difference can be ascribed, at least partly, to stronger hydrogen bonding of FA to DMSO than to water in the corresponding solutions, examined by a combination of IR spectroscopic and quantum chemical studies. Furthermore, the investigation of DMSO/FA- and water/FA systems by (1)H- and (13)C-NMR spectroscopy revealed that only 1 : 1 aggregates are formed in the DMSO solutions of FA in a broad concentration range, while the stoichiometry and the number of the FA-water aggregates essentially depend on the concentration of aqueous solutions. PMID- 26890150 TI - The use of decision aids on early detection of prostate cancer: views of men and general practitioners. AB - BACKGROUND AND OBJECTIVE: While decision support tools such as decision aids can contribute to shared decision making, implementing these tools in daily practice is challenging. To identify and address issues around the use of decision support tools in routine care, this study explores the views of men and general practitioners on using a DA for early detection of prostate cancer. METHODS, SETTING AND PARTICIPANTS: Group discussions and semi-structured interviews were carried out with 43 men and 16 general practitioners familiar with a previously developed decision aid. Data were analysed using qualitative description. RESULTS: Views on using the decision support tool could be classified into four categories: no need for decision making, need for support, perceived benefit and practical barriers. For each category, several underlying themes could be identified that reflect the absence or presence of prerequisites to successful decision support delivery. DISCUSSION AND CONCLUSION: While men and general practitioners generally have positive attitudes to shared decision making, for both parties attitudes such as not agreeing that there is a decision to be made and doubts on the beneficence of using DAs were identified as factors that may hinder the use of a DA in clinical practice. Participants formulated strategies to support the use of DAs, mainly supplementing DAs with short tools and investing in both training programmes and large-scale awareness raising of the general public. PMID- 26890152 TI - Modified Mesoporous Silica for Efficient Siloxane Capture. AB - In this study, octamethylcyclotetrasiloxane (D4) was removed by using a novel modified solid adsorbent of mesoporous silica. The adsorbent was synthesized using inverse micelles with some modifications in the synthesis process (temperature of gelation) and in the post treatment conditions (calcination temperature and heating rate) with a concomitant improvement of D4 uptake. This is the first report on regulating the textural properties of the mesoporous silica material UCT-14 to develop an active silica adsorbent. These adjustments resulted in an increase of the silica surface area from 391 to 798 m(2).g(-1), which leads to a high capacity (686 mg.g(-1)) of D4-capture for the silica synthesized at 80 degrees C, calcined at 450 degrees C with the heating rate of 100 degrees C.min(-1) (Si-Syn80). This adsorbent showed comparable adsorption performance with the widely used commercial silica gel under dry and humid condition. Recyclability tests on the commercial silica gel and mesoporous silica synthesized at 120 degrees C and calcined at 450 degrees C with a heating rate of 100 degrees C.min(-1) (called Si-Syn120 or Si-450 or Si-100 degrees C.min( 1)) indicated that the Si-Syn120 (capacity drop 10%) is more efficient than silica gel (capacity drop 15%) after three cycles. Although, the presence of moisture (25%) in the nitrogen gas stream led to capacity reduction in both Si Syn120 and commercial silica gel, the modified UCT-14 shows slightly better resistance to humid condition. PMID- 26890153 TI - Fully Integrated Organic Nanocrystal Diode as High Performance Room Temperature NO2 Sensor. AB - Organic diodes consisting of molecular nano-pyramid structures sandwiched between metal and strained nano-membrane electrodes are created. The robust and smooth contacts provided by self-curled metal layers render the molecular nano-pyramids efficent channels for detecting nitrogen dioxide airflow. PMID- 26890155 TI - Clinical outcomes of patients infected with HIV through use of injected drugs compared to patients infected through sexual transmission: late presentation, delayed anti-retroviral treatment and higher mortality. AB - AIMS: To compare patients who acquired HIV infection through use of injected drugs (HIV-IDU) with patients who acquired HIV by sexual transmission (HIV-ST) in terms of late presentation (LP), delay in anti-retroviral treatment (ART) initiation, virological and immunological response to ART, mortality and progression to AIDS. DESIGN: Prospective multi-centre cohort study of HIV infected subjects naive to ART at entry (Cohort of the Spanish HIV Research Network: CoRIS). SETTING: Thirty-one centres from the Spanish public health-care system. PARTICIPANTS: A total of 9355 patients were included (1064 HIV-IDU and 8291 HIV-ST) during 2004-13. MEASUREMENTS: We compared LP (defined as presentation for care with a CD4 cell count < 350/MUl and/or AIDS-defining illness), delayed ART initiation (defined as initiating treatment more than 6 months after the date when treatment was indicated by the guidelines, or not initiating treatment at all when it was indicated), virological and immunological response to ART (defined as viral load < 50 HIV-1 RNA copies/ml and a CD4 count increase of at least 100 cells/MUl, respectively, after 1 year of treatment), mortality and progression to AIDS in HIV-IDU and HIV-ST. FINDINGS: Compared with HIV-ST, HIV-IDU had higher risk of LP [odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.41-2.18], delayed ART initiation (OR 1.87; 95% CI = 1.46-2.40) and higher mortality [hazard ratio (HR) = 1.43; 95% CI = 1.03-2.01] and risk of progression to AIDS [subhazard ratio (SHR) = 1.68; 95% CI = 1.29-2.18]. Virological suppression due to ART was lower in HIV-IDU than in patients with HIV ST only among patients without hepatitis C virus (HCV) infection [adjusted OR (aOR) = 0.59; 95% CI = 0.36-0.95]; among patients with HCV infection, virological suppression due to ART did not show significant differences between HIV-IDU and HIV-ST. There were no significant differences in immunological response after adjusting by HCV (aOR = 0.74; 95% CI = 0.52-1.06). CONCLUSIONS: In Spain, patients who acquire HIV infection through use of injected drugs appear to have a higher risk of late presentation, delayed initiation of anti-retroviral treatment and progression to AIDS and death than patients who acquire HIV by sexual transmission. PMID- 26890157 TI - Isolation of Sertoli Cells and Peritubular Cells from Rat Testes. AB - The testis, and in particular the male gamete, challenges the immune system in a unique way because differentiated sperm first appear at the time of puberty - more than ten years after the establishment of systemic immune tolerance. Spermatogenic cells express a number of proteins that may be seen as non-self by the immune system. The testis must then be able to establish tolerance to these neo-antigens on the one hand but still be able to protect itself from infections and tumor development on the other hand. Therefore the testis is one of a few immune privileged sites in the body that tolerate foreign antigens without evoking a detrimental inflammatory immune response. Sertoli cells play a key role for the maintenance of this immune privileged environment of the testis and also prolong survival of cotransplanted cells in a foreign environment. Therefore primary Sertoli cells are an important tool for studying the immune privilege of the testis that cannot be easily replaced by established cell lines or other cellular models. Here we present a detailed and comprehensive protocol for the isolation of Sertoli cells - and peritubular cells if desired - from rat testes within a single day. PMID- 26890158 TI - Drawing from a culture of active learning: Student-initiated peer education. PMID- 26890159 TI - Correction: Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer. PMID- 26890160 TI - Helicobacter-negative gastritis: polymerase chain reaction for Helicobacter DNA is a valuable tool to elucidate the diagnosis. AB - BACKGROUND: Helicobacter-negative gastritis has been increasingly reported. Molecular techniques as the polymerase chain reaction (PCR) may detect bacterial DNA in histologically negative gastritis. AIM: To evaluate of Helicobacter PCR in gastric biopsies for the daily diagnostics of Helicobacter-negative gastritis. METHODS: Over a 5-year period, routine biopsies with chronic gastritis reminiscent of Helicobacter infection, but negative by histology, were tested by using a H. pylori specific PCR. Subsequently, PCR-negative samples were re evaluated using PCR for other Helicobacter species. RESULTS: Of the 9184 gastric biopsies, 339 (3.7%) with histological-negative gastritis and adequate material were forwarded to PCR analysis for H. pylori and 146 (43.1%) revealed a positive result. In 193 H. pylori DNA-negative biopsies, re-analysis using PCR primers for other Helicobacter species, revealed further 23 (11.9%) positive biopsies, including 4 (2.1%) biopsies with H. heilmannii sensu lato. PCR-positive biopsies showed a higher overall inflammatory score, more lymphoid follicles/aggregates and neutrophils (P < 0.05). No Helicobacter DNA was found in control biopsies of 48 patients with neither primer set (P < 0.0001). In 274 patients with an endoscopic description, detection of H. pylori DNA was associated with ulcers and erosions (P < 0.01). Over all, in 339 histologically-negative gastric biopsies, Helicobacter DNA was detected in 169 (49.9%) samples with at least one primer set. CONCLUSION: Molecular testing offers a sensitive and specific diagnosis to a selected group of patients, in whom adequate searches for bacteria by conventional histology have resulted in the unsatisfactory diagnosis of H. pylori negative gastritis. PMID- 26890162 TI - Spinal Fractures in Patients With Ankylosing Spondylitis: Etiology, Diagnosis, and Management. AB - In patients with ankylosing spondylitis, the altered biomechanics of the spine increase the incidence of spinal fractures and the risk of subsequent displacement and neurologic injury. Radiographic evaluation is difficult and requires imaging of the entire spine and the use of advanced imaging. Nonsurgical treatment has a high rate of complications and is typically pursued only when surgical intervention would carry unacceptably high perioperative risks. The surgical approach depends on the fracture location and any deformity present. Anterior fixation alone has been associated with high failure rates; therefore, posterior or combined anterior-posterior fixation should be considered. With either nonsurgical or surgical management, complications are frequent and can result in high mortality rates; however, good outcomes can be achieved if an appropriate level of suspicion of fracture is maintained and care is taken to avoid complications related to patient transport, transfer, and positioning. PMID- 26890163 TI - Capacity Building for Rare Bleeding Disorders in the Remote Commonwealth of the Northern Mariana Islands. AB - The US Pacific Commonwealth of the Northern Mariana Islands is home to an underserved hemophilia population. We developed a strategy in 2014 to build sustainable island-wide medical, patient and family, and community support for this rare disease. Collaboration with regional bleeding disorder leadership galvanized a weeklong conference series. More than 200 participants attended discipline-specific seminars; pre-post test evaluations documented educational benefits. This time-concentrated island-wide education intervention promoted the rapid identification of new cases and stimulated sustainable bleeding disorder care development. The education series proved feasible, efficient, and effective in increasing knowledge and reducing patient and professional isolation, serving as a model for improving capacity for orphan diseases (those that affect fewer than 200 000 people in any particular country) in underresourced areas. PMID- 26890161 TI - Iron-catalyzed Cross-Coupling of Propargyl Carboxylates and Grignard Reagents: Synthesis of Substituted Allenes. AB - Presented herein is a mild, facile, and efficient iron-catalyzed synthesis of substituted allenes from propargyl carboxylates and Grignard reagents. Only 1-5 mol % of the inexpensive and environmentally benign [Fe(acac)3 ] at -20 degrees C was sufficient to afford a broad range of substituted allenes in excellent yields. The method tolerates a variety of functional groups. PMID- 26890156 TI - Infection-related and -unrelated malignancies, HIV and the aging population. AB - OBJECTIVES: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. METHODS: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. RESULTS: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/MUL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with >= 500 cells/MUL], independent of age, while a CD4 count < 200 cells/MUL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40-4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged >= 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5-5.9) per 1000 person years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2-7.2) per 1000 person-years over the same period. CONCLUSIONS: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost-benefit of screening for IURMs in HIV-infected populations. PMID- 26890164 TI - Community Health Center Utilization Following the 2008 Medicaid Expansion in Oregon: Implications for the Affordable Care Act. AB - OBJECTIVES: To assess longitudinal patterns of community health center (CHC) utilization and the effect of insurance discontinuity after Oregon's 2008 Medicaid expansion (the Oregon Experiment). METHODS: We conducted a retrospective cohort study with electronic health records and Medicaid data. We divided individuals who gained Medicaid in the Oregon Experiment into those who maintained (n = 788) or lost (n = 944) insurance coverage. We compared these groups with continuously insured (n = 921) and continuously uninsured (n = 5416) reference groups for community health center utilization rates over a 36-month period. RESULTS: Both newly insured groups increased utilization in the first 6 months. After 6 months, use among those who maintained coverage stabilized at a level consistent with the continuously insured, whereas it returned to baseline for those who lost coverage. CONCLUSIONS: Individuals who maintained coverage through Oregon's Medicaid expansion increased long-term utilization of CHCs, whereas those with unstable coverage did not. POLICY IMPLICATIONS: This study predicts long-term increase in CHC utilization following Affordable Care Act Medicaid expansion and emphasizes the need for policies that support insurance retention. PMID- 26890165 TI - Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996-2013. AB - OBJECTIVES: To describe trends in benzodiazepine prescriptions and overdose mortality involving benzodiazepines among US adults. METHODS: We examined data from the Medical Expenditure Panel Survey and multiple-cause-of-death data from the Centers for Disease Control and Prevention. RESULTS: Between 1996 and 2013, the percentage of adults filling a benzodiazepine prescription increased from 4.1% (95% confidence interval [CI] = 3.8%, 4.5%) to 5.6% (95% CI = 5.2%, 6.1%), with an annual percent change of 2.5% (95% CI = 2.1%, 3.0%). The quantity of benzodiazepines filled increased from 1.1 (95% CI = 0.9, 1.2) to 3.6 (95% CI = 3.0, 4.2) kilogram lorazepam equivalents per 100 000 adults (annual percent change = 9.0%; 95% CI = 7.6%, 10.3%). The overdose death rate increased from 0.58 (95% CI = 0.55, 0.62) to 3.07 (95% CI = 2.99, 3.14) per 100 000 adults, with a plateau seen after 2010. CONCLUSIONS: Benzodiazepine prescriptions and overdose mortality have increased considerably. Fatal overdoses involving benzodiazepines have plateaued overall; however, no evidence of decreases was found in any group. Interventions to reduce the use of benzodiazepines or improve their safety are needed. PMID- 26890166 TI - Corporate Funding for Schools of Public Health: Confronting the Ethical and Economic Challenges. AB - We discuss the public and private sponsoring of university research and the issues it raises in a context of diminished federal funding. We consider research funding at schools of public health and why these schools have historically had weaker links to industry than have other academic units. We argue that the possibility of enhanced links with industry at schools of public health may raise specific concerns beyond those facing universities generally. Six issues should be considered before entering into these relationships: (1) the effects on research orientation, (2) unacceptability of some funders, (3) potential threats to objectivity and academic freedom, (4) effects on academic standards, (5) the effects on dissemination of knowledge, and (6) reputational risks. PMID- 26890167 TI - Total Duration of Breastfeeding, Vitamin D Supplementation, and Serum Levels of 25-Hydroxyvitamin D. AB - OBJECTIVES: To determine the association between total breastfeeding duration and serum 25-hydroxyvitamin D (25-OHD) and to explore whether vitamin D supplementation influences this association. METHODS: We conducted a cross sectional study of healthy children between September 2011 and August 2013 through the TARGet Kids! primary health care research network. Of the 4533 eligible children, we included only the 2508 who had 25-OHD measured. We assessed adjusted associations of total breastfeeding duration (in months) with serum 25 OHD and in supplemented versus nonsupplemented children, with the odds of 25-OHD less than 20 nanograms per milliliter. RESULTS: Each 1-month increase in total breastfeeding duration was associated with a 0.12 nanograms per milliliter lower median serum 25-OHD (95% confidence interval [CI] = -0.21 ng/mL, -0.02 ng/mL) among children who were not supplemented. The odds of serum 25-OHD less than 20 nanograms per milliliter increased by 6% (odds ratio [OR] = 1.06; 95% CI = 1.03, 1.10) for every 1-month increase in total breastfeeding duration among nonsupplemented children. The interaction between vitamin D supplementation, duration of breastfeeding, and median serum 25-OHD was statistically significant (P = .04). CONCLUSIONS: Breastfed children who were not supplemented, particularly those breastfed more than 1 year, appear to have lower vitamin D status. Vitamin D supplementation may mitigate this risk. These findings support recommendations for supplementation during breastfeeding of any duration. PMID- 26890168 TI - Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999-2009. AB - OBJECTIVES: To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. METHODS: We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999-2009 and compared those with corresponding urban White and rural AI/AN death rates. RESULTS: The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. CONCLUSIONS: Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities. PMID- 26890170 TI - "Unleashed on an Unsuspecting World": The Asbestos Information Association and Its Role in Perpetuating a National Epidemic. AB - Examining previously underused corporate documents, we revisit the story of the Asbestos Information Association/North America, an industry trade group that sought in the early 1970s to counteract the growing public attention to, and government regulation of, asbestos as a serious threat to workers and consumers. From the mid-1960s through the early 1970s, according to its own spokesperson, asbestos was exposed as "probably the most hazardous industrial material ever unleashed on an unsuspecting world." In retrospect, thousands of lives may have been saved if the Asbestos Information Association had publicly acknowledged this earlier. PMID- 26890169 TI - Inequalities in Hospitalized Unintentional Injury Between Aboriginal and Non Aboriginal Children in New South Wales, Australia. AB - OBJECTIVES: To quantify inequalities in rates of unintentional injury-related hospitalizations between Australian Aboriginal and non-Aboriginal children. METHODS: We used linked hospital and mortality data to construct a retrospective whole-of-population birth cohort including 1,124,717 children born in the state of New South Wales, Australia, between July 1, 2000 and December 31, 2012. We adjusted hazard ratios (HRs) of first injury hospitalization for geographic clustering and individual- and area-level factors. RESULTS: Aboriginal children were 1.6 times more likely than were non-Aboriginal children to be hospitalized for an unintentional injury. The largest inequalities were for poisoning (HR = 2.7; 95% CI = 2.4, 3.0) and injuries stemming from exposure to fire, flames, heat, and hot substances (HR = 2.4; 95% CI = 2.1, 2.7). Adjustment reduced the inequality for all unintentional injury overall (HR = 1.4; 95% CI = 1.3, 1.4) and within leading injury mechanisms. CONCLUSIONS: Australian Aboriginal children suffer a disproportionately high burden of unintentional injury. PMID- 26890171 TI - Comparison of Commercial and Self-Initiated Weight Loss Programs in People With Prediabetes: A Randomized Control Trial. AB - OBJECTIVES: To determine if a widely available weight-management program (Weight Watchers) could achieve sufficient weight loss in persons with prediabetes compared with a Diabetes Prevention Program-based individual counseling program supported by National Diabetes Education Program materials. METHODS: We conducted an individual, randomized intervention trial in Indianapolis, Indiana, in 2013 to 2014, in 225 persons with prediabetes. We compared the Weight Watchers weight management program (n = 112) with Your Game Plan to Prevent Type 2 Diabetes, a program developed by the National Diabetes Education Program. Outcomes were weight and metabolic markers measured at baseline, 6 months, and 12 months. RESULTS: Intervention participants lost significantly more weight than controls at 6 months (5.5% vs 0.8%) and 12 months (5.5% vs 0.2%; both P < .001). The intervention group also had significantly greater improvements in hemoglobin A1c and high-density lipoprotein cholesterol level than did controls. CONCLUSIONS: A large weight-management program is effective for achieving lifestyle changes associated with diabetes prevention. Such programs could significantly increase the availability of diabetes prevention programs worldwide making an immediate and significant public health impact. PMID- 26890173 TI - Tobacco-Free Pharmacy Laws and Trends in Tobacco Retailer Density in California and Massachusetts. AB - OBJECTIVES: To examine the impact of local laws prohibiting tobacco sales in pharmacies in California and Massachusetts, the only 2 US states in which such municipal laws exist. METHODS: We analyzed longitudinally the tobacco retailer density at the city level from tobacco retailer license data in California (2005 2013) and Massachusetts (2004-2014). RESULTS: After adjustments, the reduction in tobacco retailer density over time was 1.44 (95% confidence interval [CI] = 1.37, 1.51) to 3.18 (95% CI = 1.11, 5.25) times greater in cities with a tobacco-free pharmacy law than in cities without such a law. CONCLUSIONS: Tobacco-free pharmacy laws are associated with a greater reduction in tobacco retailer density over time in California and Massachusetts. PMID- 26890172 TI - Impact of Universal Health Coverage on Child Growth and Nutrition in Argentina. AB - OBJECTIVES: To estimate trends of undernutrition (stunting and underweight) among children younger than 5 years covered by the universal health coverage programs Plan Nacer and Programa Sumar. METHODS: From 2005 to 2013, Plan Nacer and Programa Sumar collected high-quality information on birth and visit dates, age (in days), gender, weight (in kg), and height (in cm) for 1.4 million children in 6386 health centers (13 million records) with broad coverage of vulnerable populations in Argentina. RESULTS: The prevalence of stunting and underweight decreased 45.0% (from 20.6% to 11.3%) and 38.0% (from 4.0% to 2.5%), respectively, with differences between rural versus urban areas, gender, regions, age, and seasons. CONCLUSIONS: Undernutrition prevalence substantially decreased in 2 programs in Argentina as a result of universal health coverage. PMID- 26890174 TI - Increase in Naloxone Prescriptions Dispensed in US Retail Pharmacies Since 2013. AB - Distribution of naloxone, traditionally through community-based naloxone programs, is a component of a comprehensive strategy to address the epidemic of prescription opioid and heroin overdose deaths in the United States. Recently, there has been increased focus on naloxone prescription in the outpatient setting, particularly through retail pharmacies, yet data on this practice are sparse. We found an 1170% increase in naloxone dispensing from US retail pharmacies between the fourth quarter of 2013 and the second quarter of 2015. These findings suggest that prescribing naloxone in the outpatient setting complements traditional community-based naloxone programs. PMID- 26890175 TI - Reconciling Epidemiology and Social Justice in the Public Health Discourse Around the Sexual Networks of Black Men Who Have Sex With Men. AB - Several studies have implicated the sexual networks of Black men who have sex with men (MSM) as facilitating disproportionally high rates of new HIV infections within this community. Although structural disparities place these networks at heightened risk for infection, HIV prevention science continues to describe networks as the cause for HIV disparities, rather than an effect of structures that pattern infection. We explore the historical relationship between public health and Black MSM, arguing that the current articulation of Black MSM networks is too often incomplete and counterproductive. Public health can offer a counternarrative that reconciles epidemiology with the social justice that informs our discipline, and that is required for an effective response to the epidemic among Black MSM. PMID- 26890178 TI - Quantifying Distance Overestimation From Global Positioning System in Urban Spaces. AB - OBJECTIVES: To investigate accuracy of distance measures computed from Global Positioning System (GPS) points in New York City. METHODS: We performed structured walks along urban streets carrying Globalsat DG-100 GPS Data Logger devices in highest and lowest quartiles of building height and tree canopy cover. We used ArcGIS version 10.1 to select walks and compute the straight-line distance (Geographic Information System-measured) and sum of distances between consecutive GPS waypoints (GPS-measured) for each walk. RESULTS: GPS distance overestimates were associated with building height (median overestimate = 97% for high vs 14% for low building height) and to a lesser extent tree canopy (43% for high vs 28% for low tree canopy). CONCLUSIONS: Algorithms using distances between successive GPS points to infer speed or travel mode may misclassify trips differentially by context. Researchers studying urban spaces may prefer alternative mode identification techniques. PMID- 26890176 TI - The Effect of Community-Based Prevention and Care on Ebola Transmission in Sierra Leone. AB - OBJECTIVES: To examine the acceptability, use, effects on early isolation, and contribution to Ebola virus disease (EVD) transmission of Community Care Centers (CCCs), which were rapidly deployed in Sierra Leone during an accelerated phase of the 2014-2015 EVD epidemic. METHODS: Focus group discussions, triads, and key informant interviews assessed acceptability of the CCCs. Facility registers, structured questionnaires, and laboratory records documented use, admission, and case identification. We estimated transmission effects by comparing time between symptom onset and isolation at CCCs relative to other facilities with the national Viral Hemorrhagic Fever data set. RESULTS: Between November 2014 and January 2015, 46 CCCs were operational. Over 13 epidemic weeks, 6129 patients were triaged identifying 719 (12%) EVD suspects. Community acceptance was high despite initial mistrust. Nearly all patients presented to CCCs outside the national alert system. Isolation of EVD suspects within 4 days of symptoms was higher in CCCs compared with other facilities (85% vs 49%; odds ratio = 6.0; 95% confidence interval = 4.0, 9.1), contributing to a 13% to 32% reduction in the EVD reproduction number (Ro). CONCLUSIONS: Community-based approaches to prevention and care can reduce Ebola transmission. PMID- 26890180 TI - National Needs of Family Planning Among US Men Aged 15 to 44 Years. AB - OBJECTIVES: To estimate national need for family planning services among men in the United States according to background characteristics, access to care, receipt of services, and contraception use. METHODS: We used weighted data from the 2006-2010 National Survey of Family Growth to estimate the percentage of men aged 15 to 44 years (n = 10 395) in need of family planning, based on sexual behavior, fecundity, and not trying to get pregnant with his partner. RESULTS: Overall, 60% of men were in need of family planning, defined as those who ever had vaginal sex, were fecund, and had fecund partner(s) who were not trying to get pregnant with partner or partner(s) were not currently pregnant. The greatest need was among young and unmarried men. Most men in need of family planning had access to care, but few reported receiving family planning services (< 19%), consistently using condoms (26%), or having partners consistently using contraception (41%). CONCLUSIONS: The need for engaging men aged 15 to 44 years in family planning education and care is substantial and largely unmet despite national public health priorities to include men in reducing unintended pregnancies. PMID- 26890179 TI - Homeopathy Use by US Adults: Results of a National Survey. AB - We used the 2012 National Health Interview Survey to compare homeopathy users with supplement users and those using other forms of complementary and integrative medicine. Among US adults, 2.1% used homeopathy within the past 12 months. Respiratory and otorhinolaryngology complaints were most commonly treated (18.5%). Homeopathy users were more likely to use multiple complementary and integrative medicine therapies and to perceive the therapy as helpful than were supplement users. US homeopathy use remains uncommon; however, users perceive it as helpful. PMID- 26890181 TI - Evaluation of the Evidence Base for the Alcohol Industry's Actions to Reduce Drink Driving Globally. AB - OBJECTIVES: To evaluate the evidence base for the content of initiatives that the alcohol industry implemented to reduce drink driving from 1982 to May 2015. METHODS: We systematically analyzed the content of 266 global initiatives that the alcohol industry has categorized as actions to reduce drink driving. RESULTS: Social aspects public relations organizations (i.e., organizations funded by the alcohol industry to handle issues that may be damaging to the business) sponsored the greatest proportion of the actions. Only 0.8% (n = 2) of the sampled industry actions were consistent with public health evidence of effectiveness for reducing drink driving. CONCLUSIONS: The vast majority of the alcohol industry's actions to reduce drink driving does not reflect public health evidenced-based recommendations, even though effective drink-driving countermeasures exist, such as a maximum blood alcohol concentration limit of 0.05 grams per deciliter for drivers and widespread use of sobriety checkpoints. PMID- 26890177 TI - Effects of Community-Based Health Worker Interventions to Improve Chronic Disease Management and Care Among Vulnerable Populations: A Systematic Review. AB - BACKGROUND: Community-based health workers (CBHWs) are frontline public health workers who are trusted members of the community they serve. Recently, considerable attention has been drawn to CBHWs in promoting healthy behaviors and health outcomes among vulnerable populations who often face health inequities. OBJECTIVES: We performed a systematic review to synthesize evidence concerning the types of CBHW interventions, the qualification and characteristics of CBHWs, and patient outcomes and cost-effectiveness of such interventions in vulnerable populations with chronic, noncommunicable conditions. SEARCH METHODS: We undertook 4 electronic database searches-PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane-and hand searched reference collections to identify randomized controlled trials published in English before August 2014. SELECTION: We screened a total of 934 unique citations initially for titles and abstracts. Two reviewers then independently evaluated 166 full-text articles that were passed onto review processes. Sixty-one studies and 6 companion articles (e.g., cost-effectiveness analysis) met eligibility criteria for inclusion. DATA COLLECTION AND ANALYSIS: Four trained research assistants extracted data by using a standardized data extraction form developed by the authors. Subsequently, an independent research assistant reviewed extracted data to check accuracy. Discrepancies were resolved through discussions among the study team members. Each study was evaluated for its quality by 2 research assistants who extracted relevant study information. Interrater agreement rates ranged from 61% to 91% (average 86%). Any discrepancies in terms of quality rating were resolved through team discussions. MAIN RESULTS: All but 4 studies were conducted in the United States. The 2 most common areas for CBHW interventions were cancer prevention (n = 30) and cardiovascular disease risk reduction (n = 26). The roles assumed by CBHWs included health education (n = 48), counseling (n = 36), navigation assistance (n = 21), case management (n = 4), social services (n = 7), and social support (n = 18). Fifty-three studies provided information regarding CBHW training, yet CBHW competency evaluation (n = 9) and supervision procedures (n = 24) were largely underreported. The length and duration of CBHW training ranged from 4 hours to 240 hours with an average of 41.3 hours (median: 16.5 hours) in 24 studies that reported length of training. Eight studies reported the frequency of supervision, which ranged from weekly to monthly. There was a trend toward improvements in cancer prevention (n = 21) and cardiovascular risk reduction (n = 16). Eight articles documented cost analyses and found that integrating CBHWs into the health care delivery system was associated with cost-effective and sustainable care. CONCLUSIONS: Interventions by CBHWs appear to be effective when compared with alternatives and also cost effective for certain health conditions, particularly when partnering with low income, underserved, and racial and ethnic minority communities. Future research is warranted to fully incorporate CBHWs into the health care system to promote noncommunicable health outcomes among vulnerable populations. PMID- 26890183 TI - Hepatitis C Screening Rate Among Underserved Adults With Serious Mental Illness Receiving Care in California Community Mental Health Centers. AB - Although HCV is more prevalent among people with severe mental illness (SMI; e.g., schizophrenia, bipolar disorder) than in the general population (17% vs 1%), no large previous studies have examined HCV screening in this population. In this cross-sectional study, we examined administrative data for 57 170 California Medicaid enrollees with SMI to identify prevalence and predictors of HCV screening from October 2010 through September 2011. Only 4.7% (2674 of 57 170) received HCV screening, with strongest predictors being nonpsychiatric health care utilization and comorbid substance abuse. PMID- 26890182 TI - Disability and Risk of Recent Sexual Violence in the United States. AB - OBJECTIVES: To examine the relative prevalence of recent (past 12 months) penetrative and nonpenetrative sexual violence comparing men and women with and without a disability. METHODS: Data are from the 2010 National Intimate Partner and Sexual Violence Survey, a national telephone survey of US adults, and includes an expansive measure of sexual violence victimization. A total of 9086 women and 7421 men completed the telephone survey in 2010. RESULTS: Compared with persons without a disability, persons with a disability were at increased risk for recent rape for women (adjusted odds ratio = 3.3; 95% confidence interval = 1.6, 6.7), and being made to penetrate a perpetrator for men (adjusted odds ratio = 4.2; 95% confidence interval = 1.6, 10.8). An estimated 39% of women raped in the 12 months preceding the survey had a disability at the time of the rape. For women and men, having a disability was associated with an increased risk of sexual coercion and noncontact unwanted sexual experiences. CONCLUSIONS: In this nationally representative sample, men and women with a disability were at increased risk for recent sexual violence, compared to those without a disability. PMID- 26890184 TI - Gender-Specific Jealousy and Infidelity Norms as Sources of Sexual Health Risk and Violence Among Young Coupled Nicaraguans. AB - Gender inequity negatively affects health in Central America. In 2011, we conducted 60 semistructured interviews and 12 photovoice focus groups with young coupled men and women in Leon, Nicaragua, to explore the ways in which social norms around marriage and gender affect sexual health and gender-based violence. Participants' depictions of their experiences revealed gendered norms around infidelity that provided a narrative to justify male expressions of jealousy, which included limiting partner autonomy, sexual coercion, and physical violence against women, and resulted in increased women's risk of sexually transmitted infections, including HIV. By understanding and taking account of these different narratives and normalized beliefs in developing health- and gender-based violence interventions, such programs might be more effective in promoting gender equitable attitudes and behaviors among young men and women in Nicaragua. PMID- 26890185 TI - Human Papillomavirus Vaccination in the United States: Uneven Uptake by Gender, Race/Ethnicity, and Sexual Orientation. AB - OBJECTIVES: To assess national differences in human papillomavirus (HPV) vaccine uptake among young adults in the United States by gender, race/ethnicity, and sexual orientation. METHODS: We tested group differences in initiation and completion of the HPV vaccine series (i.e., 3 doses) by Rao-Scott chi(2) test among 6444 respondents aged 18 to 30 years from the 2013 National Health Interview Survey. RESULTS: Among men, 5% reported receiving the HPV vaccine, with no differences in uptake by race/ethnicity or sexual orientation. By contrast, 30% of the women reported receiving the HPV vaccine, with women of color having lower odds of initiating and completing the vaccine series compared with White women. CONCLUSIONS: In the United States, HPV vaccine rates are lagging in men and show disparities among women. Increasing HPV vaccine uptake and series completion among women of color and all men may provide considerable long-term public health benefits. PMID- 26890186 TI - Refugee Resettlement Patterns and State-Level Health Care Insurance Access in the United States. AB - We sought to evaluate the relationship between state-level implementation of the Patient Protection and Affordable Care Act (ACA) and resettlement patterns among refugees. We linked federal refugee resettlement data to ACA expansion data and found that refugee resettlement rates are not significantly different according to state-level insurance expansion or cost. Forty percent of refugees have resettled to states without Medicaid expansion. The wide state-level variability in implementation of the ACA should be considered by federal agencies seeking to optimize access to health insurance coverage among refugees who have resettled to the United States. PMID- 26890187 TI - Chemical fragment arrays for rapid druggability assessment. AB - Incorporation of early druggability assessment in the drug discovery process provides a means to prioritize target proteins for high-throughput screening. We present chemical fragment arrays as a method that is capable of determining the druggability of a given target with low protein and compound consumption, enabling rapid decision making during early phases of drug discovery. PMID- 26890188 TI - Synthesis, characterization and toxicological evaluation of Cr2O3 nanoparticles using Daphnia magna and Aliivibrio fischeri. AB - Chromium III oxide (Cr2O3) nanoparticles (NPs) are used in pigments for ceramics, dyes, paints and cosmetics. However, few studies addressing the toxic potential of these NPs have been reported in the literature. Thus, this research aimed to evaluate the acute and chronic effects of Cr2O3 NPs through acute toxicity tests with Daphnia magna and Aliivibrio fischeri and chronic toxicity tests with Daphnia magna. Cr2O3 NPs were synthesized by the sol-gel method and characterized through TEM, X-Ray diffraction (XRD), zeta potential (ZP) and surface area analysis. In the acute toxicity tests the EC(50,48h) value obtained with D. magna was 6.79 mg L(-1) and for A. fischeri the EC(50,15min) value was 16.10 mg L(-1) and the EC(50,30min) value was 12.91 mg L(-1). Regarding the chronic toxicity tests with D. magna, effects on longevity (OEC=1.00 mg L(-1)), reproduction (OEC=1.00 mg L(-1)) and growth (OEC=0.50 mg L(-1)) were observed. On the SEM and TEM images, ultrastructural alterations in the organelles of exposed organisms were also observed. Thus, toxicological studies with NPs are of great importance in order to reduce the risk of environmental contamination. PMID- 26890189 TI - Landfill leachate treatment using bacto-algal co-culture: An integrated approach using chemical analyses and toxicological assessment. AB - The present study aims to evaluate the feasibility of leachate treatment using a synergistic approach by microalgae and bacteria. Leachate from one of the landfill of Northern India showed the presence of various toxic organic contaminants like naphthalene, benzene, phenol and their derivatives, napthols, pesticides, epoxides, phthalates and halogenated organic compounds. ICP-AES analysis revealed high concentrations of Zn, Cr, Fe, Ni, and Pb beyond the maximum permissible limit of discharge. Bacto-algal co-culture was found to be the most efficient in removal of toxic organic contaminants and heavy metals. Further, detoxification efficiency of bacto-algal treatment was evaluated by Methyl tetrazolium (MTT) assay for cytotoxicity and alkaline comet assay for genotoxicity using hepatoma HepG2 cells. Reduction in toxicity was confirmed by an increase in LC50 by 1.9 fold and reduction in Olive Tail Moment by 40.6 fold after 10 days of treatment. Results of the study indicate bioremediation and detoxification potency of bacto-algal co-culture for leachate treatment. PMID- 26890191 TI - Re: Assessment of Stone Complexity for PCNL: A Systematic Review of the Literature, How Best Can We Record Stone Complexity in PCNL? (From: Withington J, Armitage J, Finch W, et al. J Endourol 2016;30:13-23). PMID- 26890190 TI - Application of quantitative structure-property relationship analysis to estimate the vapor pressure of pesticides. AB - The application of molecular descriptors in describing Quantitative Structure Property Relationships (QSPR) for the estimation of vapor pressure (VP) of pesticides is of ongoing interest. In this study, QSPR models were developed using multiple linear regression (MLR) methods to predict the vapor pressure values of 162 pesticides. Several feature selection methods, namely the replacement method (RM), genetic algorithms (GA), stepwise regression (SR) and forward selection (FS), were used to select the most relevant molecular descriptors from a pool of variables. The optimum subset of molecular descriptors was used to build a QSPR model to estimate the vapor pressures of the selected pesticides. The Replacement Method improved the predictive ability of vapor pressures and was more reliable for the feature selection of these selected pesticides. The results provided satisfactory MLR models that had a satisfactory predictive ability, and will be important for predicting vapor pressure values for compounds with unknown values. This study may open new opportunities for designing and developing new pesticide. PMID- 26890192 TI - Nocturnal Hypertension and Subclinical Cardiac and Carotid Damage: An Updated Review and Meta-Analysis of Echocardiographic Studies. AB - Evidence on the association of nocturnal hypertension (NH) with subclinical cardiac and vascular damage is scanty. The authors performed a meta-analysis to provide comprehensive information on this clinically relevant issue. Full articles providing data on subclinical cardiac and carotid damage as assessed by ultrasonographic methods in patients with NH as compared with patients with nocturnal normotension (NN) were considered. A total of 3657 patients (NH=2083, NN=1574) of both sexes were included in seven studies. Left ventricular mass index was higher in individuals with NH than in those with NN (112+/-4.7 g/m(2) vs 98+/-4.8 g/m(2) ; standard mean difference [SMD], 0.54+/-0.16; confidence interval [CI], 0.23-0.85; P<.01). Similarly, common carotid intima-media thickness was greater in patients with NH than in those with NN (751+/-34 MUm vs 653+/-14 MUm; SMD, 0.44+/-0.08; CI, 0.29-0.59; P<.01). The present meta-analysis shows an association between NH pattern and increased likelihood of cardiac and carotid structural alterations. PMID- 26890193 TI - Sonographic and clinical effects of botulinum toxin Type A combined with extracorporeal shock wave therapy on spastic muscles of children with cerebral palsy. AB - OBJECTIVE: The aim of this study was to compare the combined sonographic and clinical effects of botulinum toxin type A (BoNT-A) and extracorporeal shock wave therapy (ESWT) versus BoNT-A alone in children with cerebral palsy. METHODS: Ten children with spastic cerebral palsy were randomly assigned to one of two groups. Group 1 received BoNT-A injection into the spastic muscles of the affected limbs plus three ESWT sessions. Group 2 received BoNT-A alone. Assessment was performed before and 1 month after injection. Sonographic outcomes were injected muscles echo intensity and their hardness percentage, and clinical outcomes the modified Ashworth scale and the Tardieu scale. RESULTS: At 1-month evaluation, significant differences in the injected muscles percentage of hardness (P = 0.021) and the modified Ashworth scale (P = 0.001) were found between groups. CONCLUSIONS: Our results support the hypothesis that the combined effects of BoNT-A and ESWT derive from their respective action on neurological and non-neural rheological components in spastic muscles. PMID- 26890194 TI - Continuous Infusion Vancomycin Through the Addition of Vancomycin to the Continuous Renal Replacement Therapy Solution in the PICU: A Case Series. AB - OBJECTIVES: To describe our experience with achieving therapeutic serum vancomycin concentrations in pediatric continuous renal replacement therapy by using continuous infusion vancomycin by mixing vancomycin into the continuous renal replacement therapy solution. DESIGN: Retrospective chart review. SETTING: A 189-bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Pediatric patients receiving continuous renal replacement therapy from April 1, 2009, through December 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were a total of 21 patients who received continuous renal replacement therapy during the study period. Of these, 11 (52.3%) received vancomycin in the continuous renal replacement therapy solution. The median (range) concentration of vancomycin added to the continuous renal replacement therapy solution was 25 mg/L (18-35 mg/L). The mean vancomycin plateau level was 22.8 +/- 3.3 mg/L. All patients achieved a serum vancomycin plateau level that was greater than 15 mg/L. There were no adverse events related to the addition of vancomycin to the continuous renal replacement therapy solution. CONCLUSIONS: The addition of vancomycin to the continuous renal replacement therapy solution(s) is an effective modality that is used for delivering vancomycin continuous infusion and for ensuring therapeutic vancomycin serum plateau levels in the setting of pediatric continuous renal replacement therapy. Further studies are required to evaluate whether this delivery method can lead to improved patient outcomes. PMID- 26890195 TI - Neonatal Type II Alveolar Epithelial Cell Transplant Facilitates Lung Reparation in Piglets With Acute Lung Injury and Extracorporeal Life Support. AB - OBJECTIVES: Type II alveolar epithelial cells have potential for lung growth and reparation. Extracorporeal membrane oxygenation is used as life support for lung impairment resulting from acute respiratory distress syndrome. We hypothesized that intratracheal transplantation of isogeneic primary type II alveolar epithelial cells in combination with extracorporeal membrane oxygenation may facilitate lung reparation for acute lung injury (ALI). DESIGN: A randomized, controlled experiment. SETTING: An animal laboratory in a university pediatric center. SUBJECTS: Twenty-eight 4- to 6-week young piglets, weighing 7-8 kg. INTERVENTIONS: Type II alveolar epithelial cells from neonatal male piglet lungs were isolated, purified, cultured, and labeled with chemical stain PKH26. After 3 6 hours of induction of ALI by IV endotoxin and mechanical ventilation (MV), young female piglets were allocated to five groups (n = 5): ALI-MV, ALI treated with MV; ALI-EC, ALI treated with both MV and venovenous extracorporeal membrane oxygenation; ALI-EC-T, ALI-EC protocol plus intratracheal type II alveolar epithelial cell transplant; CON-MV, healthy animals treated with MV; and CON-EC T, healthy animals treated with venovenous extracorporeal membrane oxygenation. After 24 hours, animals were weaned from treatment for recovery in the ensuing 14 days, with their lungs assessed for injury and reparation. MEASUREMENTS AND MAIN RESULTS: Lung injury for animals in ALI-MV was moderate to severe, whereas much milder injuries in ALI-EC-T and ALI-EC were found. More PKH26-labeled type II alveolar epithelial cells were detected by fluorescence in the lungs of ALI-EC-T than in CON-EC-T as further verified by the expression of messenger RNA of sex determining region of Y chromosome. Electromicroscopically intact type II alveolar epithelial cells and prominent lattice-like tubular myelin were also found in ALI-EC-T and CON-MV but not in ALI-EC. The hydroxyproline level in lung tissue was significantly lower in ALI-EC-T than in ALI-EC and ALI-MV, with most of the lung histopathologic and pathobiologic manifestations in favor of ALI-EC T. CONCLUSIONS: The preliminary data suggested that type II alveolar epithelial cell transplant facilitated lung reparation for ALI in this model. PMID- 26890196 TI - The Impact of Observed Trauma on Parents in a PICU. AB - OBJECTIVE: To explore parents' experiences of "observed trauma," defined as traumatic events, unrelated to their own child, that parents/carers witness while in a PICU. DESIGN: Exploratory qualitative study. SETTING: Nineteen-bed mixed surgical/medical PICU in a tertiary university-affiliated children's hospital. PARTICIPANTS: Parents of 11 children, screened from a total sample of 100 children admitted to the PICU for greater than 48 hours. INTERVENTIONS: Face-to face screening interviews were conducted with parents following their child's discharge from PICU. Parents who reported observed trauma were interviewed a second time to explore their experiences. MEASUREMENTS AND MAIN RESULTS: Two questionnaires were designed, one to screen for observed trauma and a second one to guide semistructured interviews. Of 100 parents who participated in a structured screening interview, 19% reported observed trauma. Of the 19 parents, 11 completed the second interview. Significant themes included: involuntary exposure; privacy and confidentiality; empathy for children and their families; reflection and personal growth; and staff communication. CONCLUSIONS: Observed trauma is not uncommon in the PICU. The results suggest that timely support may alleviate the short-term negative impact. Furthermore, some parents have reported positive aspects to their experience. PMID- 26890197 TI - Parental Physical Proximity in End-of-Life Care in the PICU. AB - OBJECTIVE: Health professionals in PICUs support both child and parents when a child's death is imminent. Parents long to stay connected to their dying child but the high-tech environment and treatment implications make it difficult to stay physically close. This study explores in what sense physical aspects of end of-life care in the PICU influence the parent-child relationship. DESIGN: Retrospective, qualitative interview study. SETTING: Level 3 PICU in Erasmus Medical Center in the Netherlands. PARTICIPANTS: Thirty-six parents of 20 children who had died in this unit 5 years previously. MEASUREMENTS AND MAIN RESULTS: Parents vividly remembered the damage done to the child's physical appearance, an inevitable consequence of medical treatment. They felt frustrated and hurt when they could not hold their child. Yet they felt comforted if facilitated to be physically close to the dying child, like lying with the child in one bed, holding the child in the hour of death, and washing the child after death. CONCLUSIONS: End-of-life treatment in the PICU presents both a barrier and an opportunity for parents to stay physically connected to their child. Parents' experiences suggest that aspects of physicality in medical settings deserve more attention. Better understanding of the significance of bodily aspects-other than pain and symptom management-improves end-of-life support and should be part of the humane approach to families. PMID- 26890198 TI - Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study. AB - OBJECTIVE: We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. DESIGN: Prospective observational cohort study. SETTING: Two eight-bed PICUs of a tertiary-care university hospital. PATIENTS: A heterogeneous population of critically ill children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. CONCLUSIONS: Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction. PMID- 26890199 TI - Optimal Chest Compression Position for Patients With a Single Ventricle During Cardiopulmonary Resuscitation. AB - OBJECTIVES: Few studies have examined cardiopulmonary resuscitation for patients with congenital heart disease, although they are at a high risk of cardiac arrest. Therefore, this study investigated the optimal chest compression position in patients with a single ventricle while providing them with basic life support. DESIGN: This is a retrospective study of patients with a single ventricle who are undergoing chest CT. SETTING: Tertiary teaching children's hospital. PATIENTS: A total of 185 patients with a single ventricle, including 73 patients before a bidirectional cavopulmonary shunt, 61 patients after a bidirectional cavopulmonary shunt, and 51 patients after the Fontan operation. INTERVENTIONS: Chest CT scans were reviewed. MEASUREMENTS AND MAIN RESULTS: Sternal length was defined as the distance from the suprasternal notch to the xiphisternal junction. The optimal level of external cardiac compression was defined as the level at which the cross-sectional area of the systemic ventricle was the largest. The distance from the suprasternal notch to this level over the sternum was calculated. The structures below the intermammary line, the lower half and the lower third of the sternum, and the optimal level were determined. The level with the largest cross-sectional area of the ventricle was approximately the lower fourth of the sternum in all surgical stages: 86.5% +/- 4.9% of the sternal length from the suprasternal notch before bidirectional cavopulmonary shunt, 85.9% +/- 4.8% after bidirectional cavopulmonary shunt, and 86.4% +/- 6.3% after the Fontan operation. The liver was not identified at any level, whereas the ascending aorta was detected in 2.2%, 3.8%, and 24.9% at the level of the lower third of the sternum, the intermammary line, and the lower half of the sternum, respectively. CONCLUSIONS: The optimal compression position in patients with a single ventricle is approximately 5-25% of the lower sternum. The optimal compression level for patients with a single ventricle is lower than that suggested in current guidelines for the normal population. PMID- 26890201 TI - Instantiating informatics in nursing practice for integrated patient centred holistic models of care: a discussion paper. AB - AIM: A discussion on how informatics knowledge and competencies can enable nursing to instantiate transition to integrated models of care. BACKGROUND: Costs of traditional models of care are no longer sustainable consequent to the spiralling incidence and costs of chronic illness. The international community looks towards technology-enabled solutions to support a shift towards integrated patient-centred models of care. DESIGN: Discussion paper. DATA SOURCES: A search of the literature was performed dating from 2000-2015 and a purposeful data sample based on relevance to building the discussion was included. DISCUSSION: The holistic perspective of nursing knowledge can support and advance integrated healthcare models. Informatics skills are key for the profession to play a leadership role in design, implementation and operation of next generation health care. However, evidence suggests that nursing engagement with informatics strategic development for healthcare provision is currently variable. IMPLICATIONS FOR NURSING: A statistically significant need exists to progress health care towards integrated models of care. Strategic and tactical plans that are robustly pragmatic with nursing insights and expertise are an essential component to achieve effective healthcare provision. To avoid exclusion in the discourse dominated by management and technology experts, nursing leaders must develop and actively promote the advancement of nursing informatics skills. For knowledge in nursing practice to flourish in contemporary health care, nurse leaders will need to incorporate informatics for optimal translation and interpretation. CONCLUSION: Defined nursing leadership roles informed by informatics are essential to generate concrete solutions sustaining nursing practice in integrated care models. PMID- 26890200 TI - Diagnosis and Treatment of Ventilator-Associated Infection: Review of the Critical Illness Stress-Induced Immune Suppression Prevention Trial Data. AB - OBJECTIVES: The Critical Illness Stress-Induced Immune Suppression prevention trial was a randomized, masked trial of zinc, selenium, glutamine, and metoclopramide compared with whey protein in delaying nosocomial infection in PICU patients. One fourth of study subjects were diagnosed with nosocomial lower respiratory infection, which contributed to subjects receiving antibiotics 74% of all patient days in the PICU. We analyzed diagnostic and treatment variability among the participating institutions and compared outcomes between nosocomial lower respiratory infection subjects (n = 74) and intubated subjects without nosocomial infection (n = 1 55). DESIGN: Post hoc analysis. SETTING: Eight hospitals in the Collaborative Pediatric Critical Care Research Network. PATIENTS: Critical Illness Stress-Induced Immune Suppression study subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Variability across institutions existed in the frequency and manner by which respiratory secretion cultures were obtained, processed, and results reported. Most results were reported semiquantitatively, and both Gram stains and antibiotic sensitivities were frequently omitted. The nosocomial lower respiratory infection diagnosis was associated with increased PICU lengths of stay compared with those who were intubated without nosocomial infection (24 +/- 19 vs 9 +/- 6 d; p < 0.001) and antibiotic use (38 +/- 29 vs 15 +/- 20 antibiotics days; p < 0.001). Despite antibiotic treatment, the same bacteria persisted in 45% of follow-up cultures. CONCLUSIONS: The Critical Illness Stress-Induced Immune Suppression data demonstrate that the nosocomial lower respiratory infection diagnosis is associated with longer lengths of stay and increased antibiotic use, but there is considerable diagnostic and treatment variability across institutions. More rigorous standards for when and how respiratory cultures are obtained, processed, and reported are necessary. Bacterial persistence also complicates the interpretation of follow-up cultures. PMID- 26890202 TI - Metallic Ternary Telluride with Sphalerite Superstructure. AB - A new ternary compound with composition Cu5Sn2Te7 has been synthesized using the stoichiometric reaction of Cu, Sn, and Te. The compound crystallizes in C2 space group with unit cell parameters of a = 13.549(2) A, b = 6.0521(11) A, c = 9.568(2) A, and beta = 98.121(2) degrees . Cu5Sn2Te7 is a superstructure of sphalerite and exhibits tetrahedral coordination of Cu, Sn, and Te atoms, containing a unique adamantane-like arrangement. The compound is formally mixed valent with a high electrical conductivity of 9.8 * 10(5) S m(-1) at 300 K and exhibits metallic behavior having p-type charge carriers as indicated from the positive Seebeck coefficient. Hall effect measurements further confirm holes as charge carriers with a carrier density of 1.39 * 10(21) cm(-3) and Hall mobility of 4.5 cm(2) V(-1) s(-1) at 300 K. The electronic band structure calculations indicate the presence of a finite density of states around the Fermi level and agree well with the p-type metallic conductivity. Band structure analysis suggests that the effective mass of the hole state is small and could be responsible for high electronic conductivity and Hall mobility. The high thermal conductivity of 15.1 W m(-1) K(-1) at 300 K coupled with the low Seebeck coefficient results in a poor thermoelectric figure of merit (ZT) for this compound. Theoretical calculations indicate that if Cu5Sn2Te7 is turned into a valence precise compound by substituting one Cu by a Zn, a semiconducting material, Cu4ZnSn2Te7, with a direct band gap of ~ 0.5 eV can be obtained. PMID- 26890204 TI - Structural characterization and vibrational studies of human urinary stones from Istanbul, Turkey. AB - Seven human urinary stones were collected from urinary bladders of patients hailing from Istanbul, Turkey. Their XRD, EDX, FT-IR and FT-Raman spectra as well as SEM images have been recorded to determine their chemical compositions, morphologies, crystal structures, and crystallite sizes. XRD and vibrational (FT IR and FT-Raman) analyses indicate that six out of the seven stones have identical contents. The ratios of organic and inorganic contents of the stones have been determined by their thermogravimetric analyses. The stones have been found to contain calcium oxalate monohydrate and apatite as the major components. PMID- 26890205 TI - Competitive removal of hazardous dyes from aqueous solution by MIL-68(Al): Derivative spectrophotometric method and response surface methodology approach. AB - MIL-68(Al) as a metal-organic framework (MOF) was synthesized and characterized by different techniques such as SEM, BET, FTIR, and XRD analysis. This material was then applied for simulations removal of malachite green (MG) and methylene blue (MB) dyes from aqueous solutions using second order derivative spectrophotometric method (SODS) which was applied to resolve the overlap between the spectra of these dyes. The dependency of dyes removal efficiency in binary solutions was examined and optimized toward various parameters including initial dye concentration, pH of the solution, adsorbent dosage and ultrasonic contact time using central composite design (CCD) under response surface methodology (RSM) approach. The optimized experimental conditions were set as pH7.78, contact time 5min, initial MB concentration 22mgL(-1), initial MG concentration 12mgL(-1) and adsorbent dosage 0.0055g. The equilibrium data was fitted to isotherm models such as Langmuir, Freundlich and Tempkin and the results revealed the suitability of the Langmuir model. The maximum adsorption capacity of 666.67 and 153.85mgg( 1) was obtained for MB and MG removal respectively. Kinetics data fitting to pseudo-first order, pseudo-second order and Elovich models confirmed the applicability of pseudo-second order kinetic model for description of the mechanism and adsorption rate. Dye-loaded MIL-68(Al) can be easily regenerated using methanol and applied for three frequent sorption/desorption cycles with high performance. The impact of ionic strength on removal percentage of both dyes in binary mixture was studied by using NaCl and KCl soluble salts at different concentrations. According to our findings, only small dosage of the proposed MOF is considerably capable to remove large amounts of dyes at room temperature and in very short time that is a big advantage of MIL-68(Al) as a promising adsorbent for adsorptive removal processes. PMID- 26890207 TI - Pharmacologic approaches to the prevention and management of low bone mineral density in HIV-infected patients. AB - PURPOSE OF REVIEW: Osteoporosis is a growing concern among people living with HIV (PLWH) because of the recognized risk of fractures, which bring with them morbidity and mortality. New evidence is helping clinicians understand how to prevent and manage osteoporosis in this subpopulation. RECENT FINDINGS: The benefit of calcium and vitamin D is variable in osteoporosis literature in general, but evidence supports the use of these supplements in PLWH to prevent the loss of bone mineral density when initiating antiretroviral therapy and in enhancing the effectiveness of antiosteoporosis treatments. Of the osteoporosis treatments, alendronate and zoledronate are the only two with substantial evidence of safety and effectiveness in PLWH, but the studies have been small and of limited duration. There are no randomized controlled studies of raloxifene, denosumab or teriparatide in PLWH. Of increasing interest is the possible benefit of statins on bone health through decreased inflammation. SUMMARY: Osteoporosis is recognized as an issue for PLWH. Although some of the available osteoporosis treatments have proven safe and effective, future studies of the novel treatments, such as statins, along with well-designed studies of established osteoporosis treatments for use in PLWH are needed to further guide the clinical management of osteoporosis in this population. PMID- 26890206 TI - Hepatitis C virus coinfection as a risk factor for osteoporosis and fracture. AB - PURPOSE OF REVIEW: With increased survival of HIV-infected patients, osteoporotic fractures have developed as a major cause of morbidity in these patients, and chronic hepatitis C virus (HCV) coinfection has emerged as a significant contributor to this increased fracture risk. The present article reviews the epidemiologic and clinical evidence for osteoporosis and increased fracture risk among HIV/HCV coinfected patients, and potential mechanisms for these outcomes with HCV coinfection. RECENT FINDINGS: Epidemiologic studies suggest that HIV/HCV coinfected patients exhibit a three-fold increased fracture incidence compared with uninfected controls, and 1.2-2.4-fold increased fracture risk compared with HIV monoinfected patients. Recent reports suggest that chronic HCV coinfection is independently associated with reduced bone mineral density in HIV, but that it is not associated with significantly increased bone turnover. The deleterious impact of chronic HCV on BMD and fracture risk occurs even in the absence of advanced liver fibrosis or cirrhosis. New tools to assess bone quality, including the trabecular bone score, high-resolution peripheral quantitative computed tomography, and in-vivo microindentation, may help improve understanding of the mechanisms of HCV-associated skeletal fragility. The impact of approved antiosteoporosis medications and direct-acting antivirals for the treatment of chronic HCV infection on patients' bone health remain to be studied. SUMMARY: Chronic HCV infection is an independent risk factor for osteoporosis and fractures among HIV-infected patients, even before the development of cirrhosis. The underlying mechanisms are being unraveled, but major questions persist regarding the optimal evaluation and management of bone health in HIV/HCV coinfected patients. PMID- 26890203 TI - Molecular mechanisms of biological aging in intervertebral discs. AB - Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1289-1306, 2016. PMID- 26890208 TI - Bone health in HIV-infected children and adolescents. AB - PURPOSE OF REVIEW: Chronic HIV infection and exposure to antiretroviral therapy compromises bone health in children and adolescents, potentially impacting their long-term quality of life. Thus, the purpose of this article is to review the most recent literature on this topic in HIV-infected children and adolescents. RECENT FINDINGS: Recent studies continue to demonstrate bone abnormalities in HIV infected children and adolescents, whether HIV is acquired perinatally or during adolescence. Researchers have employed new modalities, both high tech and those that can be utilized in resource-limited settings, to better assess bone health. New data suggest that this population may also be experiencing an increase incidence of fractures, and they may not acquire the same peak bone mass as their HIV-uninfected counterparts. Reassuringly, however, in-utero tenofovir exposure does not appear to have a significant impact on bone health in HIV-exposed, uninfected infants. SUMMARY: HIV-infected children and adolescents are exposed to HIV and antiretroviral therapy for many decades starting early in life and during the most critical time for skeletal growth and bone mass accrual. Recent findings underscore the need for further research on bone in this population. Longitudinal studies are especially needed to evaluate long-term risk of osteoporosis and fracture. PMID- 26890211 TI - Treatment of Mycobacterium abscessus Infection. AB - Mycobacterium abscessus is often resistant to multiple antimicrobial drugs, and data supporting effective drugs or dosing regimens are limited. To better identify treatment approaches and associated toxicities, we collected a series of case reports from the Emerging Infections Network. Side effects were common and often led to changing or discontinuing therapy. PMID- 26890210 TI - Genome-wide methylation analysis of retrocopy-associated CpG islands and their genomic environment. AB - Gene duplication by retrotransposition, i.e., the reverse transcription of an mRNA and integration of the cDNA into the genome, is an important mechanism in evolution. Based on whole-genome bisulfite sequencing of monocyte DNA, we have investigated the methylation state of all CpG islands (CGIs) associated with a retrocopy (n = 1,319), their genomic environment, as well as the CGIs associated with the ancestral genes. Approximately 10% of retrocopies are associated with a CGI. Whereas almost all CGIs of the human genome are unmethylated, 68% of the CGIs associated with a retrocopy are methylated. In retrocopies resulting from multiple retrotranspositions of the same ancestral gene, the methylation state of the CGI often differs. There is a strong positive correlation between the methylation state of the CGI/retrocopy and their genomic environment, suggesting that the methylation state of the integration site determined the methylation state of the CGI/retrocopy, or that methylation of the retrocopy by a host defense mechanism has spread into the adjacent regions. Only a minor fraction of CGI/retrocopies (n = 195) has intermediate methylation levels. Among these, the previously reported CGI/retrocopy in intron 2 of the RB1 gene (PPP1R26P1) as well as the CGI associated with the retrocopy RPS2P32 identified in this study carry a maternal methylation imprint. In conclusion, these findings shed light on the evolutionary dynamics and constraints of DNA methylation. PMID- 26890212 TI - Scenario Discovery with Multiple Criteria: An Evaluation of the Robust Decision Making Framework for Climate Change Adaptation. AB - There is increasing concern over deep uncertainty in the risk analysis field as probabilistic models of uncertainty cannot always be confidently determined or agreed upon for many of our most pressing contemporary risk challenges. This is particularly true in the climate change adaptation field, and has prompted the development of a number of frameworks aiming to characterize system vulnerabilities and identify robust alternatives. One such methodology is robust decision making (RDM), which uses simulation models to assess how strategies perform over many plausible conditions and then identifies and characterizes those where the strategy fails in a process termed scenario discovery. While many of the problems to which RDM has been applied are characterized by multiple objectives, research to date has provided little insight into how treatment of multiple criteria impacts the failure scenarios identified. In this research, we compare different methods for incorporating multiple objectives into the scenario discovery process to evaluate how they impact the resulting failure scenarios. We use the Lake Tana basin in Ethiopia as a case study, where climatic and environmental uncertainties could impact multiple planned water infrastructure projects, and find that failure scenarios may vary depending on the method used to aggregate multiple criteria. Common methods used to convert multiple attributes into a single utility score can obscure connections between failure scenarios and system performance, limiting the information provided to support decision making. Applying scenario discovery over each performance metric separately provides more nuanced information regarding the relative sensitivity of the objectives to different uncertain parameters, leading to clearer insights on measures that could be taken to improve system robustness and areas where additional research might prove useful. PMID- 26890213 TI - Development and evaluation of targeting ligand-anchored CNTs as prospective targeted drug delivery system. AB - Our main investigation in the present research was to developt and evaluate targeting ligand-anchored multiwalled carbon nanotubes (MWCNTs) as prospective targeted drug delivery system, with a special focus on the MWCNTs surface functionalization (FA-PEG bis-amine functionalized, carboxylated MWCNTs). In vitro release of 5-fluorouracil (5-FU) was studied at pH 7.4 phosphate buffer and 5.5 acetate buffer, which displayed initial faster followed by sustained release up to 900 min. Further, 5-FU/FA-PEG bis amine-MWCNTs was found to be long circulating, prolonged half-life and increased drug accumulation in target tissue. PMID- 26890214 TI - Prevalence of Healthy Sleep Duration among Adults--United States, 2014. AB - To promote optimal health and well-being, adults aged 18-60 years are recommended to sleep at least 7 hours each night (1). Sleeping <7 hours per night is associated with increased risk for obesity, diabetes, high blood pressure, coronary heart disease, stroke, frequent mental distress, and all-cause mortality (2-4). Insufficient sleep impairs cognitive performance, which can increase the likelihood of motor vehicle and other transportation accidents, industrial accidents, medical errors, and loss of work productivity that could affect the wider community (5). CDC analyzed data from the 2014 Behavioral Risk Factor Surveillance System (BRFSS) to determine the prevalence of a healthy sleep duration (>= 7 hours) among 444,306 adult respondents in all 50 states and the District of Columbia. A total of 65.2% of respondents reported a healthy sleep duration; the age-adjusted prevalence of healthy sleep was lower among non Hispanic blacks, American Indians/Alaska Natives, Native Hawaiians/Pacific Islanders, and multiracial respondents, compared with non-Hispanic whites, Hispanics, and Asians. State-based estimates of healthy sleep duration prevalence ranged from 56.1% in Hawaii to 71.6% in South Dakota. Geographic clustering of the lowest prevalence of healthy sleep duration was observed in the southeastern United States and in states along the Appalachian Mountains, and the highest prevalence was observed in the Great Plains states. More than one third of U.S. respondents reported typically sleeping <7 hours in a 24-hour period, suggesting an ongoing need for public awareness and public education about sleep health; worksite shift policies that ensure healthy sleep duration for shift workers, particularly medical professionals, emergency response personnel, and transportation industry personnel; and opportunities for health care providers to discuss the importance of healthy sleep duration with patients and address reasons for poor sleep health. PMID- 26890209 TI - Vitamin D and bone loss in HIV. AB - PURPOSE OF REVIEW: Bone health has become an increasingly important aspect of the care of HIV-infected patients as bone loss with antiretroviral therapy (ART) initiation is significant and osteopenia and osteoporosis are highly prevalent. Vitamin D is tightly linked to calcium balance and bone health, and vitamin D deficiency is common in HIV. This review outlines the epidemiology of vitamin D deficiency in HIV, summarizes our current understanding of the relationship between vitamin D and bone loss in HIV and the impact of vitamin D supplementation in this patient group. RECENT FINDINGS: Although data are conflicting as to whether vitamin D deficiency is more prevalent among HIV infected individuals than in the general population, there are several reasons for why this patient group may be at heightened risk. Studies linking vitamin D deficiency to bone loss in HIV are limited; however, data from randomized clinical trials suggest a benefit of vitamin D supplementation for the prevention of bone loss with ART initiation and for the treatment of bone loss with bisphosphonate therapy. SUMMARY: There are too limited data to recommend universal screening of vitamin D status or supplementation to all HIV-infected individuals. However, testing 25-hydroxyvitamin D levels in those at risk for deficiency and treating patients found to be deficient or initiating ART or bisphosphonate therapy should be considered. Further study on vitamin D supplementation is needed regarding the potential benefit on immune activation and restoration in this patient group. PMID- 26890216 TI - Ordered La0.7Sr0.3MnO3 nanohole arrays fabricated on a nanoporous alumina template by pulsed laser ablation. AB - Highly ordered nanohole arrays of [Formula: see text] manganite have been synthesized using pulsed laser deposition on nanoporous alumina template. Their structure and phase formation were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), energy dispersive x-ray spectroscopy (EDX) and x-ray diffraction (XRD). The magnetic measurements were performed with respect to temperature and field and exhibit a ferromagnetic to paramagnetic transition at 284 K. In addition, the temperature dependence of electrical resistance was measured at different magnetic fields and an insulating phase throughout all the temperatures was observed. The low temperature ferromagnetic insulating state is discussed by the presence of a canted ferromagnetic state induced by the nanoholes. The present work shows the feasibility of combining both the nanoporous alumina template and pulsed laser ablation for the fabrication of perovskite manganite nanohole arrays which can also be extended to fabricate other multicomponent oxide nanohole materials. PMID- 26890215 TI - Tuberculosis, Fiji, 2002-2013. AB - During 2002-2013, a total of 1,890 tuberculosis cases were recorded in Fiji. Notification rates per 100,000 population increased from 17.4 cases in 2002 to 28.4 in 2013. Older persons were most affected, but tuberculosis also increased sharply in persons 25-44 years of age. PMID- 26890217 TI - MicroRNA profile analysis of host cells before and after wild human rotavirus infection. AB - Rotavirus infection is an important cause of acute gastroenteritis in children, but the interaction between rotavirus and host cells is not completely understood. We isolated a wildtype (wt) rotavirus strain, ZTR-68(P [8] G1), which is derived from an infant with diarrhea in southwest China in 2010. In this study, we investigated host cellular miRNA expression profiles changes in response to ZTR-68 in early stage of infection to investigate the role of miRNAs upon rotavirus infection. Differentially expressed miRNAs were identified by deep sequencing and qRT-PCR and the function of their targets predicted by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. A total of 36 candidate miRNAs were identified. Comparative analysis indicated that 29 miRNAs were significantly down-regulated and 7 were up regulated after infection. The data were provided contrasting the types of microRNAs in two different permissive cell lines (HT29 and MA104). The target assays results showed that mml-miR-7 and mml-miR-125a are involved in anti rotavirus and virus-host interaction in host cells. These results offer clues for identifying potential candidates in vector-based antiviral strategies. J. Med. Virol. 88:1497-1510, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890221 TI - Effects of artificial tears on rabbit ocular surface healing after exposure to benzalkonium chloride. AB - The aim of the study was to observe the effect of different artificial tears on healing the drug-induced keratopathy. To this aim, 64 rabbits received topical administration of 0.01% benzalkonium chloride to establish models and were divided into four groups. The control group received ocular saline solution (Saline), while the others were treated with Refresh Plus(r) (RF), Hycosan(r) (H) and Systane(r) Ultra (SU). Surface abnormalities were examined daily using slit lamp. Fluorescein staining, histopathological and transmission electron microscopic (TEM) examination were performed at day 0, 2 weeks, and 1 and 2 months. A significant difference was observed between RF and SU, but not between H and SU at 2 weeks. TEM examination revealed new microvilli close to the cavity surface, and the number of microvilli in SU was greater than in H at 2 weeks and 1 month. Based on the results, the effect in the SU group was the most significant. Eye drops with nontoxic preservative such as SU are an alternative to treat drug-induced keratopathy. PMID- 26890219 TI - Cbfb2 Isoform Dominates More Potent Cbfb1 and Is Required for Skeletal Development. AB - Cbfb is a cotranscription factor that forms a heterodimer with Runx proteins Runx1, Runx2, and Runx3. It is required for fetal liver hematopoiesis and skeletal development. Cbfb has two functional isoforms, Cbfb1 and Cbfb2, which are formed by alternative splicing. To address the biological functions of these isoforms in skeletal development, we examined Cbfb1(-/-) and Cbfb2(-/-) mouse embryos. Intramembranous and endochondral ossification was retarded and chondrocyte and osteoblast differentiation was inhibited in Cbfb2(-/-) embryos but not in Cbfb1(-/-) embryos. Cbfb2 mRNA was upregulated in calvariae, limbs, livers, thymuses, and hearts of Cbfb1(-/-) embryos but Cbfb1 mRNA was not in those of Cbfb2(-/-) embryos, and the total amount of Cbfb1 and Cbfb2 mRNA in Cbfb1(-/-) embryos was similar to that in wild-type embryos but was severely reduced in Cbfb2(-/-) embryos. The absolute numbers of Cbfb2 mRNA in calvariae, limbs, livers, thymuses, and brains in wild-type embryos were about three times higher than those of Cbfb1 in the respective tissue. The levels of Runx proteins were reduced in calvariae, limbs, and primary osteoblasts from Cbfb2(-/-) embryos, but the reduction in Runx2 protein was very mild. Furthermore, the amounts of Runx proteins and Cbfb in Cbfb2(-/-) embryos differed similarly among skeletal tissues, livers, and thymuses, suggesting that Runx proteins and Cbfb are mutually required for their stability. Although Cbfb1(-/-) embryos developed normally, Cbfb1 induced chondrocyte and osteoblast differentiation and enhanced DNA binding of Runx2 more efficiently than Cbfb2. Our results indicate that modulations in the relative levels of the isoforms may adjust transcriptional activation by Runx2 to appropriate physiological levels. Cbfb2 was more abundant, but Cbfb1 was more potent for enhancing Runx2 activity. Although only Cbfb2 loss generated overt skeletal phenotypes, both may play major roles in skeletal development with functional redundancy. (c) 2016 American Society for Bone and Mineral Research. PMID- 26890220 TI - Healthcare professionals' views on discussing fertility preservation with young cancer patients: a mixed method systematic review of the literature. AB - OBJECTIVE: In spite of efforts to guarantee patients are adequately informed about their risk of fertility loss and offered treatment for fertility preservation (FP), previous studies have reported that this topic is not routinely discussed with patients, especially with younger patient populations. A mixed method systematic review was undertaken to explore the factors shaping the discussion of FP with children (0-15 years) and adolescents/young adults (16-24 years) with cancer. METHODS: Six databases were searched independently using a combination of keywords and controlled vocabulary/subject headings relating to cancer and fertility. Inclusion criteria consisted of: (a) being published in a peer-reviewed journal, (b) a focus on healthcare professionals' (HCPs') beliefs, attitudes, or practices regarding fertility issues in cancer patients, (c) primary data collection from HCPs, and (d) a focus on HCPs who provide services to young patients. Of the 6276 articles identified in the search, 16 articles presenting the results of 14 studies were included in the final review. RESULTS: Common themes reported across studies indicate that five main factors influence HCPs' discussion of FP with young cancer patients: (a) HCPs' knowledge, (b) HCPs' sense of comfort, (c) patient factors (i.e., sexual maturity, prognosis, partnership status, and whether or not they initiate the conversation), (d) parent factors (i.e., HCPs' perception of the extent of their involvement), and (e) availability of educational materials. CONCLUSIONS: Future work should ensure that HCPs possess knowledge of cancer-related FP and that they receive adequate training on how to consent and discuss information with young patients and their parents. PMID- 26890218 TI - Functions of the cellular prion protein, the end of Moore's law, and Ockham's razor theory. AB - Since its discovery the cellular prion protein (encoded by the Prnp gene) has been associated with a large number of functions. The proposed functions rank from basic cellular processes such as cell cycle and survival to neural functions such as behavior and neuroprotection, following a pattern similar to that of Moore's law for electronics. In addition, particular interest is increasing in the participation of Prnp in neurodegeneration. However, in recent years a redefinition of these functions has begun, since examples of previously attributed functions were increasingly re-associated with other proteins. Most of these functions are linked to so-called "Prnp-flanking genes" that are close to the genomic locus of Prnp and which are present in the genome of some Prnp mouse models. In addition, their role in neuroprotection against convulsive insults has been confirmed in recent studies. Lastly, in recent years a large number of models indicating the participation of different domains of the protein in apoptosis have been uncovered. However, after more than 10 years of molecular dissection our view is that the simplest mechanistic model in PrP(C)-mediated cell death should be considered, as Ockham's razor theory suggested. PMID- 26890222 TI - The organic and strategic growth of interprofessionalism in athletic training. PMID- 26890224 TI - Facile Synthesis of Fe3O4/GCs Composites and Their Enhanced Microwave Absorption Properties. AB - Graphene has good stability and adjustable dielectric properties along with tunable morphologies, and hence can be used to design novel and high-performance functional materials. Here, we have reported a facile synthesis method of nanoscale Fe3O4/graphene capsules (GCs) composites using the combination of catalytic chemical vapor deposition (CCVD) and hydrothermal process. The resulting composite has the advantage of unique morphology that offers better synergism among the Fe3O4 particles as well as particles and GCs. The microwave absorbing characteristics of developed composites were investigated through experimentally measured electromagnetic properties and simulation studies based on the transmission line theory, explained on the basis of eddy current, natural and exchange resonance, as well as dielectric relaxation processes. The composites bear minimum RL value of -32 dB at 8.76 GHz along with the absorption bandwidth range from 5.4 to 17 GHz for RL lower than -10 dB. The better performance of the composite based on the reasonable impedance characteristic, existence of interfaces around the composites, and the polarization of free carriers in 3D GCs that make the as-prepared composites capable of absorbing microwave more effectively. These results offer an effective way to design high performance functional materials to facilitate the research in electromagnetic shielding and microwave absorption. PMID- 26890223 TI - Geographic variation in suicide rates in Australian farmers: Why is the problem more frequent in Queensland than in New South Wales? AB - Research on farmer suicide is limited in explaining the variations in farmers' demographic characteristics. This study examines farmer suicides in two Australian states: Queensland (QLD) and New South Wales (NSW). Standardized suicide rates over 2000-2009 showed a 2 times higher prevalence of suicide in QLD than NSW (147 vs. 92 cases, respectively). Differences in age and suicide method were observed between states, although they do not appear to account for the sizeable intra- and interstate variations. Suicide prevention initiatives for farmers should account for different age groups and also specific place-based risk factors that may vary between and within jurisdictions. PMID- 26890225 TI - Assessment of Chromosomal DNA Fragmentation by Quinolones in an Isogenic Collection of Escherichia coli with Defined Resistance Mechanisms. AB - The aim of this study was to investigate the potential usefulness of DNA fragmentation as a quick and simple procedure for detecting resistance to fluoroquinolones (FQ) in isogenic Escherichia coli strains harboring defined and multiple quinolone resistance mechanisms, including low-level quinolone resistance (LLQR) phenotypes. DNA fragmentation assay (Micromax((r))) was evaluated for detecting resistance to FQ in 71 isogenic strains of E. coli harboring specific quinolone resistance mechanisms frequently found in clinical isolates. These isogenic strains represent a consistent and reliable model of increasing minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP), ranging from 0.004 to 16 mg/L. According to CLSI criteria, the assay correctly identified all CIP-resistant strains (MIC >=4 mg/L). As regards susceptible strains, 96% of bacterial strains were correctly assigned as susceptible to CIP. Moreover, the procedure enabled LLQR phenotypes to be efficiently identified; this subset may show different levels of DNA damage depending on the strain, even with similar MIC. Interestingly, despite increasing the dose according to the MIC, a lower response to quinolones occurs in strains with higher MIC values. This is a simple, rapid, and reliable test for evaluating susceptibility to FQ of E. coli, including the detection of strains harboring LLQR mechanisms. PMID- 26890226 TI - Current methods to diagnose small airway disease in patients with COPD. AB - The small airways are characterized by an internal diameter < 2 mm and absence of cartilage. Approximately 10-25% of total airway resistance in healthy lungs is due to the small airways, with their contribution to total airway resistance increasing substantially in chronic obstructive pulmonary disease (COPD). As the small airways are located in the lung periphery, they are not easily evaluable, which can potentially interfere with the diagnosis (especially at early stages), monitoring, detection of responses to clinical interventions, and prognostic evaluation in COPD. Here, we will discuss the currently available methods in clinical practice to evaluate small airway disease in COPD, focusing on the concept, advantages, and disadvantages of each method. PMID- 26890227 TI - The 'WikiGuidelines' smartphone application: Bridging the gaps in availability of evidence-based smartphone mental health applications. AB - Over the past decade, there have been massive advances in technology. These advances in technology have significantly transformed various aspects of healthcare. The advent of E-health and its influence on healthcare practice also implies that there is a paradigm shift in the way healthcare professionals work. Conventionally, healthcare professionals would have to refer to books and journals for updates in treatment algorithms, but with the advent of technology, they could access this information via the web or via various smartphone applications on the go. In the field of Psychiatry, one of the commonest mental health disorder to date, with significant morbidity and mortality is that of Major depressive disorder. Routinely, clinicians and healthcare professionals are advised to refer to standard guidelines in guiding them with regards to their treatment options. Given the high prevalence of conditions like Major Depressive Disorder, it is thus of importance that whatever guidelines that clinicians and healthcare professionals refer to are constantly kept up to date, so that patients could benefit from latest evidence based therapy and treatment. A review of the current literature highlights that whilst there are a multitude of smartphone applications designed for mental health care, previous systematic review has highlighted a paucity of evidence based applications. More importantly, current literature with regards to provision of treatment information to healthcare professionals and patients are limited to web-based interventions. It is the aim of this technical note to highlight a methodology to which the authors have conceptualized in the implementation of an evidence based mental health guideline applications, known as the 'Wiki Guidelines' smartphone application. The authors hope to illustrate the algorithms behind the development of the application, and how it could be easily updated by the guidelines working group. PMID- 26890228 TI - Analytical and computational modeling of early penetration of non-enveloped icosahedral viruses into cells. AB - BACKGROUND: As obligate intracellular parasites, all viruses penetrate target cells to initiate replication and infection. OBJECTIVE: This study introduces two approaches for evaluating the contact loads applied to a cell during early penetration of non-enveloped icosahedral viruses. METHODS: The first approach is analytical modeling which is based on Hertz's theory for the contact of two elastic bodies; here we model the virus capsid as a triangle and the cell as an order-of-magnitude larger sphere. The second approach is finite element modeling, where we simulate three types of viruses: adeno-, papilloma- and polio- viruses, each interacting with a cell section. RESULTS: We find that the peak contact pressures and forces generated at the initial virus-cell contact depend on the virus geometry - that is both size and shape. With respect to shape, we show that the icosahedral virus shape induces greater peak pressures compared to a spherical virus shape. With respect to size, it is shown that the larger the virus is the greater are the contact loads in the attacked cell. CONCLUSION: Utilization of our modeling can be substantially useful not only for basic science studies, but also in other, more applied fields, such as in the field of gene therapy, or in 'phage' virus studies. PMID- 26890229 TI - Global outreach and user preferences of a smartphone application developed for drinkers. AB - INTRODUCTION: Alcohol use disorders has been known and recently highlighted by the World Health Organization as a major worldwide problem. Harmful usage of alcohol has been linked to increased morbidity and mortality arising from common alcohol related disorders, such as liver disease, hypertension and violent deaths. Looking at the current literature, there have been previous peer reviewed publications about how technology has helped alcohol users. Of significance, a previous content analysis showed that the vast majority of the applications catered for alcohol use disorder which are currently available on the stores are not only not supported by evidence-base, but some of them seemed to be promoting drinking instead. Zhang et al. have described how they have attempted to overcome the limitations of current alcohol applications in their video feature recently published. OBJECTIVE: The objective of this article is to evaluate (a) the receptiveness of the general population toward an alcohol tracker application and to determine (b) user preferences with regards to the different features present in an alcohol tracker. METHODS: Android Java Developmental kit (ADK) was utilized to program the core functions of the applications. The entire developmental process took approximately 6 weeks to complete and the android version of the application was launched and offered for free download on the android play store since the 4th of February 2015. The utilization of the application was then monitored and recorded using Google analytics. User perspectives with regards to the individual features of the application were collated via an application feedback survey embedded within the application. RESULTS: Based on the analytics, a total of 339 users have had access to the application. A cumulative total of 2029 downloads of the application have been made to date. Most of the participants are male (66%) and are of the age group of 30-39 years old (34%). The vast majority of the participants (94%) do not have any prior treatment for alcohol. Interestingly, the vast majority of the users have indicated that they have a drink 4 or more times a week (61%) and tend to drink between 3 to 4 drinks on a typical day they are out drinking. the vast majority reported that they were slightly and moderately comfortable with managing their alcohol use problem (25%). After the usage of the application, 27% of the individuals were moderately comfortable with managing their alcohol use problems and 20% of individuals were extremely comfortable with managing their alcohol use problems. CONCLUSION: In conclusion, this is perhaps one of the first few studies to demonstrate the receptiveness of an alcohol tracker that has included other behavioral change methods within as well as a variant of the conventional methodology of tracking alcohol consumption. The current study shows the receptiveness of global users as well as how such an intervention could help them gain more control about managing their underlying alcohol issue. PMID- 26890230 TI - Mirror Therapy with Neuromuscular Electrical Stimulation for improving motor function of stroke survivors: A pilot randomized clinical study. AB - OBJECTIVE: This study was to investigate the effects of Mirror Therapy (MT) combined with Neuromuscular Electrical Stimulation (NMES) on muscle strength and tone, motor function, balance, and gait ability in stroke survivors with hemiplegia. METHODS: This study was a randomized controlled trial. Twenty-seven hemiplegic stroke survivors from a rehabilitation center participated in the study. The participants were randomly assigned to either an experimental or a control group. The experimental group (n = 14) underwent MT combined with NMES and conventional physical therapy, and the control group (n = 13) underwent conventional physical therapy alone. Muscle strength and tone, balance, and gait ability were examined at baseline and after 4 weeks of intervention. A hand-held dynamometer was used to assess muscle strength, the Modified Ashworth Scale (MAS) was used to assess muscle tone, the Berg Balance Scale (BBS) and Timed Up and Go test (TUG) were used to ascertain balance, and the 6-m Walk Test (6mWT) was used to examine gait ability. RESULTS: After the intervention, compared to baseline values, there were significant improvements in muscle strength and MAS, BBS, TUG, and 6mWT values in the experimental group (P< 0.05). In addition, at post intervention, there were significant differences between the two groups in muscle strength and BBS (P< 0.05). CONCLUSION: MT combined with NMES may effectively improve muscle strength and balance in hemiplegic stroke survivors. However, further studies are necessary to demonstrate brain reorganization after MT combined with NMES. PMID- 26890231 TI - A portable respiratory rate estimation system with a passive single-lead electrocardiogram acquisition module. AB - BACKGROUND: Among vital signs of acutely ill hospital patients, respiratory rate (RR) is a highly accurate predictor of health deterioration. OBJECTIVE: This study proposes a system that consists of a passive and non-invasive single-lead electrocardiogram (ECG) acquisition module and an ECG-derived respiratory (EDR) algorithm in the working prototype of a mobile application. METHOD: Before estimating RR that produces the EDR rate, ECG signals were evaluated based on the signal quality index (SQI). The SQI algorithm was validated quantitatively using the PhysioNet/Computing in Cardiology Challenge 2011 training data set. The RR extraction algorithm was validated by adopting 40 MIT PhysioNet Multiparameter Intelligent Monitoring in Intensive Care II data set. RESULTS: The estimated RR showed a mean absolute error (MAE) of 1.4 compared with the ''gold standard'' RR. The proposed system was used to record 20 ECGs of healthy subjects and obtained the estimated RR with MAE of 0.7 bpm. CONCLUSION: Results indicate that the proposed hardware and algorithm could replace the manual counting method, uncomfortable nasal airflow sensor, chest band, and impedance pneumotachography often used in hospitals. The system also takes advantage of the prevalence of smartphone usage and increase the monitoring frequency of the current ECG of patients with critical illnesses. PMID- 26890234 TI - Intracoronary platelet and monocyte activation status within platelet-monocyte complexes are determinants of inflammation in ST elevation myocardial infarction1. AB - INTRODUCTION: Platelet Monocyte Complexes (PMCs) are commonly expressed in coronary artery disease but their pathologic significance in ST elevation myocardial infarction (STEMI) is unclear. This study evaluates the relationship between locally activated PMCs and intracoronary inflammation in stable and unstable coronary disease. MATERIAL AND METHODS: Micro catheter aspirated blood samples of 15 STEMI and 7 stable angina patients are collected from the coronary artery (CA), aorta (AO) and right atrium (RA). Samples are labelled with monoclonal antibodies and prepared for flow cytometry. CD 14 and CD 61 double positive cells are identified as PMC. P-selectin expression is identified by additional CD62P positivity and TF expression by additional CD142 positivity. Plasma TNF-alpha and IL-6 are measured using ELISA and CRP is measured in plasma using a high sensitivity automated microparticle enhanced latex turbidimetric immunoassay. RESULTS: No site-specific difference is seen in overall PMC expression in STEMI or stable angina. Surface P-selectin expression in STEMI [median (IQR)] is significantly higher in CA [35.01 (23.15-56.99)] compared with AO [15.99 (10.3-18.85)] or RA [14.02 (10.42-26.08)] (p = 0.003). Intracoronary PMC correlates significantly with intracoronary TNF-alpha (r = 0.87, p = 0.001) and intracoronary IL-6 (r = 0.76, p = 0.03). Bound monocytes within P-selectin positive and tissue factor positive complexes correlate positively with intracoronary TNF-alpha (r = 0.81, p = 0.008 & r = 0.80, p = 0.009 respectively) and IL-6 (r = 0.54, p = 0.16 & r = 0.71, p = 0.05 respectively). No such correlation is observed in the peripheral circulation of STEMI and stable angina patients. CONCLUSION: Inflammation is not attributable to PMC formation per se. However, increased intracoronary P-selectin expression by activated platelets and tissue factor expression by activated monocytes within the complexes are determinants of local intracoronary inflammatory burden in STEMI. PMID- 26890232 TI - Lingonberries reduce atherosclerosis in Apoe(-/-) mice in association with altered gut microbiota composition and improved lipid profile. AB - SCOPE: To investigate the efficacy of lingonberries in prevention of atherosclerosis, using atherosclerosis-prone Apoe(-/-) mice and to clarify whether effects were associated with changes in the gut microbiota, gut metabolites, and lipid metabolism. METHODS AND RESULTS: Male Apoe(-/-) mice were fed either low-fat diet, high-fat diet, or high-fat diet with 44% lingonberries for 8 weeks. Blood lipid profiles, hepatic gene expression, atherosclerotic plaques in the aortic root region of the heart, bacterial 16S rRNA gene profiles, and cecal short-chain fatty acids (SCFAs) were analyzed. Triglyceride levels and amount of atherosclerotic plaques decreased in the group fed lingonberries in comparison to the high-fat group. Hepatic expression of the bile acid synthesis gene Cyp7a1 was significantly upregulated in the lingonberry group. Lingonberries increased the cecal relative abundance of bacterial genera Bacteroides, Parabacteroides and Clostridium. The cecal levels of total SCFAs were significantly lower in the lingonberry group, while the cecal proportion of propionic acid was higher in mice fed lingonberries. CONCLUSION: Intake of lingonberries resulted in decreased triglyceridemia and reduced atherosclerosis. The altered gut microbiota composition and SCFA profile was associated with increased hepatic bile acid gene expression in mice fed lingonberries. PMID- 26890235 TI - Retinal vessel regulation at high altitudes1. AB - PURPOSE: To measure static and dynamic changes of retinal vessels in response to normobaric hypoxia (NH, study A) and hypobaric hypoxia (HH, study B). METHODS: Study A included 10 healthy individuals exposed to a simulated altitude of 5500 meters in a NH chamber; study B included 17 individuals studied after ascent to 3000-meter altitude. Retinal vessel diameter, response to flicker light, retinal oxygen saturation and retinal venous pressure were measured at baseline, under the corresponding hypoxia condition. The effects of macitentan, an endothelin receptor antagonist, were examined in study B. RESULTS: The mean age of participants was 34.6+/-9.3 years in study A and 36.7+/-10.8 years in study B. Retinal arterial and venous diameter increased, arterial and venous response to flicker light decreased, while retinal oxygen saturation remained stable under both experimental conditions. Retinal venous pressure increased in six individuals after ascent to 3000 meters and normalized after macitentan treatment. The occurrence of acute mountain sickness (AMS) correlated only with the decrease of arterial constriction after ascent to 3000 meters. CONCLUSIONS: Retinal arterial and venous vessels react to NH and HH with a diameter increase and an impaired response to flicker light. Macitentan was capable to normalize the increased retinal venous pressure observed at high altitudes. PMID- 26890236 TI - Red blood cell nitric oxide synthase modulates red blood cell deformability in sickle cell anemia. AB - Sickle cell anemia (SCA) is an inherited red blood cells (RBC) disorder characterized by significantly decreased RBC deformability. The present study aimed to assess whether modulation of RBC Nitric Oxide Synthase (RBC-NOS) activation could affect RBC deformability in SCA.Blood of twenty-five SCA patients was treated for 1 hour at 37 degrees C with Phosphate Buffered Saline (PBS) or PBS containing 1% of Dimethylsulfoxyde as control, L-arginine or N(5)-(1 Iminoethyl)-L-ornithine (L-NIO) to directly stimulate or inhibit RBC-NOS, insulin or wortmannin to indirectly stimulate or inhibit RBC-NOS through their effects on the PI3 Kinase/Akt pathway, and sodium nitroprusside (SNP) and 2-(4 Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) as NO donor and NO scavenger, respectively. RBC deformability was measured by ektacytometry at 3 Pa.RBC deformability significantly increased after insulin treatment and significantly decreased after L-NIO and wortmannin incubation. The other conditions did not affect deformability. Significantly increased nitrotyrosine levels, a marker of enhanced free radical generation, were detected by immunohistochemistry in SNP and insulin treated samples.These data suggest that RBC deformability of SCA can be modulated by RBC-NOS activity but also that oxidative stress may impair effectiveness of RBC-NOS produced NO. PMID- 26890237 TI - Hemorheological alterations in carotid artery stenosis. AB - BACKGROUND: Carotid artery stenosis (CAS) is not only an important risk factor of cerebrovascular events but it can also indicate generalized atherosclerosis. Hemorheological parameters are altered in CAS and in chronic cerebrovascular disorders as well, but it is controversial if hemorheological parameters could be markers of stenosis or atherosclerosis. METHODS: 107 patients were investigated, 40% of them had stroke or TIA in case history and 48% had CAS. Routine lab parameters were determined and hemorheological variables were measured: hematocrit, plasma viscosity, whole blood viscosity, red blood cell aggregation, and deformability. RESULTS: In the stenotic group whole blood viscosity and red blood cell aggregation were deteriorated (p < 0.05). Whole blood and plasma viscosity were higher and red blood cell deformability was lower in the symptomatic group (p < 0.05). Plasma viscosity and red blood cell deformability were altered in the evolving atherosclerosis group and the CAS groups compared to patients having no signs of stenosis (p < 0.05), but there was no difference among the CAS groups. CONCLUSION: Although hemorheological parameters are impaired both in CAS and chronic cerebrovascular disorders, the severity of stenosis cannot be detected based on hemorheological parameters. Our investigation suggests that alteration of hemorheological parameters could indicate carotid atherosclerosis. PMID- 26890238 TI - Regulation of red blood cell deformability is independent of red blood cell nitric oxide synthase under hypoxia. AB - The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S nitrosylation and deformability.Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (+/-sodium nitrite) with gas mixtures corresponding to in vivo intervention.Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly increased at severe hypoxia in vivo and in vitro. This was causatively induced by nitrite reduction to NO which increased S nitrosylation of RBC alpha- and beta-spectrins -a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO.The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia. PMID- 26890239 TI - The responses of glabrous and nonglabrous skin microcirculation to graded dynamic exercise and its recovery. AB - This study investigated the responses of skin blood flow (SkBF) in glabrous and nonglabrous skin to graded submaximal dynamic exercise and its recovery. We enrolled eight healthy young men with comparable maximal oxygen uptake (VO2max). Laser-Doppler flux (LDF) was assessed on the finger pulp (glabrous site) and the volar forearm (nonglabrous site) simultaneously with skin temperature, heart rate and blood pressure; cutaneous vascular conductance (CVC) was calculated. Subjects were monitored before (baseline), during and 25 minutes after incremental cycling. CVC in the pulp decreased with the onset of exercise (0.53+/-0.09AUmmHg 1 vs. baseline 1.23+/-0.25AUmmHg-1, p = 0.006), and persisted low until exercise cessation, whereas CVC in the forearm started to increase at 60% of subjects' VO2max, attaining its maximum at the highest exercise load (0.44+/-0.11AUmmHg-1 vs. baseline 0.12+/-0,03AUmmHg-1, p = 0.017). In the recovery, CVC in the pulp attained a higher plateau value compared to baseline (1.51+/-0.22AUmmHg-1, p = 0.021), interrupted by abrupt transient falls of CVC. On the forearm, CVC subsequently returned to its baseline. SkBF of glabrous and nonglabrous sites adjust in an opposite manner to graded exercise load and also differ during recovery. PMID- 26890240 TI - Shear-wave elastography of the testis in the healthy man - determination of standard values. AB - PURPOSE: Real-time shear-wave elastography (SWE) is a newly developed technique for the sonographic quantification of tissue elasticity, which already is used in the assessment of breast and thyroid lesions. Due to limited overlying tissue, the testes are ideally suited for assessment using shear wave elastography. To our knowledge, no published data exist on real-time SWE of the testes. MATERIALS AND METHODS: Sixty six male volunteers (mean age 51.86+/-18.82, range 20-86) with no known testicular pathology underwent normal B-mode sonography and multi-frame shear-wave elastography of both testes using the Aixplorer (r) ultrasound system (SuperSonic Imagine, Aix en Provence, France). Three measurements were performed for each testis; one in the upper pole, in the middle portion and in the lower pole respectively. The results were statistically evaluated using multivariate analysis. RESULTS: Mean shear-wave velocity values were similar in the inferior and superior part of the testicle (1.15 m/s) and were significantly lower in the centre (0.90 m/s). These values were age-independent. Testicular stiffness was significantly lower in the upper pole than in the rest of the testis with increasing volume (p = 0.007). CONCLUSION: Real-time shear-wave elastography proved to be feasible in the assessment of testicular stiffness. It is important to consider the measurement region as standard values differ between the centre and the testicular periphery. Further studies with more subjects may be required to define the normal range of values for each age group. Useful clinical applications could include the diagnostic work-up of patients with scrotal masses or male infertility. PMID- 26890241 TI - Substrate stiffness modulates mRNA expression profiling in breast cancer cells. AB - Identifying effective targets induced by ECM stiffness is of critical importance for treating metastatic cancer diseases, which are followed by changes in the mechanical microenvironment in cancer cells. In this study, polyacrylamide hydrogel substrates with different stiffnesses were prepared and mRNA microarrays were performed to analyze the mRNA expression profiles in breast cancer cell line SK-BR-3 grown on different stiffness substrates. The results indicated that the expressions of 1831 genes were changed significantly in the SK-BR-3 cells on the different stiffness substrates. GO and KEGG pathway analyses of the differently expressed genes in five significant profiles annotated that the most significant pathways were cell cycle, ubiquitin mediated proteolysis RNA transport and pathways in cancer. Finally, the network of genes and gene interaction based on these differently expressed genes was established, and the phosphorylation of AKT and ERK, respectively the downstreams of the PI3K and Ras signal pathways, was further validated. The genes identified in this study may represent good therapeutic targets, and further study of these targets may help to increase our understanding of the mechanisms underlying the pathological processes and therapy for metastatic breast cancer disease. PMID- 26890242 TI - Camera-based photoplethysmography in critical care patients. AB - BACKGROUND: Camera-based photoplethysmography (cbPPG) is an optical measurement technique that reveals pulsatile blood flow in cutaneous microcirculation from a distance. cbPPG has been shown to reflect pivotal haemodynamic events like cardiac ejection in healthy subjects. In addition, it provides valuable insight into intrinsic microcirculatory regulation as it yields dynamic, two-dimensional perfusion maps. In this study, we evaluate the feasibility of a clinical cbPPG application in critical care patients. METHODS: A mobile camera set-up to record faces of patients at the bed site was constructed. Videos were made during the immediate recovery after cardiac surgery under standard critical care conditions and were processed offline. Major motion artefacts were detected using an optical flow technique and suitable facial regions were manually annotated. cbPPG signals were highpass filtered and Fourier spectra out of consecutive 10s signal segments calculated for heart rate detection. Signal-to-noise ratios (SNR) of the Fourier spectra were derived as a quality measure. Reference data of vital parameters were synchronously acquired from the bed site monitoring system. RESULTS: Seventy patient videos of an average time of 28.6+/-2.8 min were analysed. Heart rate (HR) was detected within a+/-5 bpm range compared to reference in 83% of total recording time. Low SNR and HR detection failure were mostly, but not exclusively, attributed to non-physiological events like patient motion, interventions or sudden changes of illumination. SNR was reduced by low arterial blood pressure, whereas no impact of other perioperative or disease-related parameters was identified. CONCLUSION: Cardiac ejection is detectable by cbPPG under pathophysiologic conditions of cardiovascular disease and perioperative medicine. cbPPG measurements can be seamlessly integrated into the clinical work flow of critical care patients. PMID- 26890243 TI - Hydroxyethyl starch solution for extracorporeal tissue perfusion. AB - In the field of free flap transfer in reconstructive surgery, the trans- or replanted tissue always undergoes cell damage during ischemia to a more or less strong extent. In previous studies we already showed that conserving muscle transplants by means of extracorporeal perfusion over a period of 6 hours by using a crystalloid solution for perfusion. However, we observed significant edema formation. In this study we aimed at reducing the edema formation by using an iso-oncotic colloid as perfusion solution. This way we wanted to evaluate a possible new application of hydroxyl-ethyl starch in an extracorporeal setup to exploit potential benefits of the colloid.Examined parameters include the muscles' functionality with external field stimulation, histological examination and edema formation. Perfused muscles showed a statistically significant higher ability to exert force compared to nonperfused ones. These findings can be confirmed using Annexin V as marker for cell damage, as perfusion of muscle tissue limits damage significantly compared to nonperfused tissue. Substituting the electrolyte perfusion solution with a colloidal one shows the tendency to reduce the edema formation however without statistical significance. PMID- 26890244 TI - Effects of acute and chronic hematocrit modulations on blood viscosity in endurance athletes. AB - The aim of the present study was to investigate the effects of manipulating hematocrit by different methods (acute exercise, training or isovolumic hemodilution) on blood viscosity in high-level aerobic endurance athletes. We hypothesized than increasing hematocrit does not always cause a rise in blood viscosity.Sixteen endurance athletes underwent maximal exercise before and after 4 weeks of training with (LHTL; n = 10) or without (placebo; n = 6) Live High Train Low modalities. Total hemoglobin mass was measured before and after training by a carbon monoxide rebreathing technique. After training, subjects performed two maximal exercise bouts separated by isovolumic hemodilution (phlebotomy and/or plasma volume expander) to readjust red blood cell volume and plasma volume to baseline values. Blood samples were obtained before and after exercise to assess hematocrit and blood and plasma viscosity.Training session (LHTL and placebo) increased hematocrit (Hct) in all subjects but without any significant change in blood viscosity. The decrease in plasma viscosity in all groups may explain this result. Isovolumic hemodilution caused a drop of Hct without any significant change in blood viscosity at rest. Maximal exercise increased Hct, blood and plasma viscosities in both groups, regardless of isovolumic hemodilution. However, peak hemorheological values after exercise were lower after isovolumic hemodilution.In conclusion, while acute increase in Hct during exercise caused an increase of blood viscosity, the chronic increase of Hct induced by training session did not result in a rise in blood viscosity. The lowering of plasma viscosity during training may compensate for the increase of Hct, hence limiting its impact on blood viscosity. PMID- 26890245 TI - Alcohol mixed with energy drink: Use may be a consequence of heavy drinking. AB - AIMS: In recent years, studies have indicated that consumers of alcohol mixed with energy drink (AmED) are more likely to drink heavily and experience more negative consequences than consumers who avoid these beverages. Although researchers have identified a number of plausible hypotheses that explain how alcohol-energy drink co-ingestion could cause greater alcohol consumption, there has been no postulation about reverse causal relations. This paper identifies several plausible hypotheses for the observed associations between AmED consumption and greater alcohol consumption, and provides initial evidence for one such hypothesis suggesting that heavy drinking may be a determinant of AmED use. METHOD: Data collected from 511bar patrons were used to examine the plausibility of one of the proposed hypotheses, i.e., AmED is an artifact of heavy drinking. Associations between the consumption of an assortment of alcoholic beverage types and total alcohol consumption were examined at the event level, to assess whether AmED is uniquely related with greater alcohol consumption. RESULTS: Increased alcohol consumption was associated with greater odds of consuming most alcoholic beverage types; this association was not unique to AmED. CONCLUSIONS: Results support the overlooked hypothesis that AmED use is an artifact of heavy drinking. Thus, AmED consumption may be a consequence or marker of heavier drinking. Much of the existing research on alcoholic beverage types is limited in its ability to implicate any specific type of drink, including AmED, as a cause of increased alcohol consumption and related harm. More rigorous study designs are needed to examine causal relationships. PMID- 26890247 TI - Short-term total sleep deprivation alters delay-conditioned memory in the rat. AB - Short-term sleep deprivation soon after training may impair memory consolidation. Also, a particular sleep stage or its components increase after learning some tasks, such as negative and positive reinforcement tasks, avoidance tasks, and spatial learning tasks, and so forth. It suggests that discrete memory types may require specific sleep stage or its components for their optimal processing. The classical conditioning paradigms are widely used to study learning and memory but the role of sleep in a complex conditioned learning is unclear. Here, we have investigated the effects of short-term sleep deprivation on the consolidation of delay-conditioned memory and the changes in sleep architecture after conditioning. Rats were trained for the delay-conditioned task (for conditioning, house-light [conditioned stimulus] was paired with fruit juice [unconditioned stimulus]). Animals were divided into 3 groups: (a) sleep deprived (SD); (b) nonsleep deprived (NSD); and (c) stress control (SC) groups. Two-way ANOVA revealed a significant interaction between groups and days (training and testing) during the conditioned stimulus-unconditioned stimulus presentation. Further, Tukey post hoc comparison revealed that the NSD and SC animals exhibited significant increase in performances during testing. The SD animals, however, performed significantly less during testing. Further, we observed that wakefulness and NREM sleep did not change after training and testing. Interestingly, REM sleep increased significantly on both days compared to baseline more specifically during the initial 4-hr time window after conditioning. Our results suggest that the consolidation of delay-conditioned memory is sleep-dependent and requires augmented REM sleep during an explicit time window soon after training. (PsycINFO Database Record PMID- 26890248 TI - Conditioned social preference, but not place preference, produced by intranasal oxytocin in female mice. AB - Oxytocin (OT) has been implicated in a variety of mammalian reproductive and social behaviors, and the use of intranasal OT for clinical purposes is on the rise. However, basic actions of OT, including the rewarding or reinforcing properties of the drug, are currently not fully understood. In this study, the authors investigated whether intranasally administered OT has different reinforcing properties for social and nonsocial stimuli and whether such effects are variable between male and female subjects. Conditioned social preference (CSP) and conditioned place preference (CPP) paradigms were used to examine social and nonsocial reinforcing properties of OT. In CSP, the presence of a same sex unfamiliar conspecific was repeatedly paired with intranasal OT, while a different conspecific was associated with saline. The reinforcing effect of OT was assessed in a postconditioning choice test under a drug-free condition. In CPP, the 2 conspecifics were replaced with nonsocial black and white compartments. The authors found that intranasal OT (12 MUg) in females supported the formation of CSP (Experiment 1) but not CPP (Experiment 3). Neither CSP (Experiment 2) nor CPP (Experiment 4) was formed in males. Extended conditioning with higher dose OT (36 MUg), however, abolished the initial CSP in females and produced an aversion to the OT-paired stimulus mouse. Experiment 5 indicated that it was the repeated administrations rather than the higher dose that produced the abolition of the original preference. Overall, the current results demonstrate for the first time a sex- and stimulus-dependent reinforcing property of intranasal OT in mice. (PsycINFO Database Record PMID- 26890246 TI - Overexpression of cyclin D1 induces the reprogramming of differentiated epidermal cells into stem cell-like cells. AB - It has been reported that Wnt/beta-catenin is critical for dedifferentiation of differentiated epidermal cells. Cyclin D1 (CCND1) is a beta-catenin target gene. In this study, we provide evidence that overexpression of CCND1 induces reprogramming of epidermal cells into stem cell-like cells. After introducing CCND1 gene into differentiated epidermal cells, we found that the large flat shaped cells with a small nuclear-cytoplasmic ratio changed into small round shaped cells with a large nuclear-cytoplasmic ratio. The expressions of CK10, beta1-integrin, Oct4 and Nanog in CCND1 induced cells were remarkably higher than those in the control group (P < 0.01). In addition, the induced cells exhibited a high colony-forming ability and a long-term proliferative potential. When the induced cells were implanted into a wound of laboratory animal model, the wound healing was accelerated. These results suggested that overexpression of CCND1 induced the reprogramming of differentiated epidermal cells into stem cell-like cells. This study may also offer a new approach to yield epidermal stem cells for wound repair and regeneration. PMID- 26890249 TI - Rapid and label-free detection and assessment of bacteria by terahertz time domain spectroscopy. AB - Here we demonstrated the potential and applicability of terahertz (THz) spectroscopy to detect four commonly found bacteria in the infectious diseases. Besides the different spectral characteristics between bacterial species, THz absorption differences for living bacteria, dead bacteria and bacterial powder of the same species were also investigated. Our results revealed that small differences in water contents between bacterial cells account for distinct discrepancies of the absorption coefficients, which can be used for bacterial species identification. Furthermore, living and dead bacteria showed different absorption coefficients as a result of their different hydration levels, suggesting that THz spectroscopy can be used to rapidly assess the living state of bacteria under test. Our results clearly demonstrated the ability of THz spectroscopy for time-saving and label-free detection of bacteria with minimal sample preparation, potentially to be utilized for point-of-care tests in the near future. Schematic representation of bacterial detection by THz spectroscopy. Different bacteria have distinctive absorption coefficients as a result of their different water contents. PMID- 26890250 TI - Association between Birth Interval and Cardiovascular Outcomes at 30 Years of Age: A Prospective Cohort Study from Brazil. AB - BACKGROUND: Birth interval is an important and potentially modifiable factor that is associated with child health. Whether an association exists with longer-term outcomes in adults is less well known. METHODS: Using the 1982 Pelotas (Brazil) Birth Cohort Study, the association of birth interval with markers of cardiovascular health at 30 years of age was examined. Multivariable linear regression was used with birth interval as a continuous variable and categorical variable, and effect modification by gender was explored. RESULTS: Birth interval and cardiovascular data were present for 2,239 individuals. With birth interval as a continuous variable, no association was found but stratification by gender tended to show stronger associations for girls. When compared to birth intervals of <18 months, as binary variable, longer intervals were associated with increases in height (1.6 cm; 95% CI: 0.5, 2.8) and lean mass (1.7 kg; 95% CI: 0.2, 3.2). No difference was seen with other cardiovascular outcomes. CONCLUSIONS: An association was generally not found between birth interval and cardiovascular outcomes at 30 years of age, though some evidence existed for differences between males and females and for an association with height and lean mass for birth intervals of 18 months and longer. PMID- 26890253 TI - Survey of prenatal testing for genetic disorders in Japan: Recent report. AB - AIM: In order to investigate the current status of prenatal testing for genetic disorders, we conducted a multicenter retrospective questionnaire survey. METHODS: The questionnaire was sent to 105 facilities with genetic counseling systems. The questionnaire consisted of two parts: (i) the number of prenatal tests conducted for genetic disorders from January 2010 to December 2012, whether the laboratory was combined with the counseling facility or separate, the sampling procedure method, the testing results, and the outcomes of the affected fetus in addition to treatment; and (ii) a survey of personal comments regarding prenatal testing for genetic disorders. RESULTS: We received responses from 69 of the 105 facilities (65.7%), and genetic testing was performed at 26 of these facilities. Nucleic acid sequential testing was performed on 45 disorders and 252 cases during a three-year period. There were 67 cases of affected fetuses. Six cases continued pregnancy and were treated. The comment survey highlighted difficulties in locating a laboratory to assess prenatal samples, as well as inadequate counseling and preparation for genetic disorders. CONCLUSIONS: Our study revealed that a number of prenatal testing for genetic disorders are conducted in Japan; however, it is difficult for counselors to locate a laboratory capable of testing for specific genetic disorders. Inadequate counseling and healthcare providers' lack of knowledge is a current problem. A well-established system of prenatal testing for genetic disorders and the further education of general physicians is required. PMID- 26890252 TI - SETD7 Regulates the Differentiation of Human Embryonic Stem Cells. AB - The successful use of specialized cells in regenerative medicine requires an optimization in the differentiation protocols that are currently used. Understanding the molecular events that take place during the differentiation of human pluripotent cells is essential for the improvement of these protocols and the generation of high quality differentiated cells. In an effort to understand the molecular mechanisms that govern differentiation we identify the methyltransferase SETD7 as highly induced during the differentiation of human embryonic stem cells and differentially expressed between induced pluripotent cells and somatic cells. Knock-down of SETD7 causes differentiation defects in human embryonic stem cell including delay in both the silencing of pluripotency related genes and the induction of differentiation genes. We show that SETD7 methylates linker histone H1 in vitro causing conformational changes in H1. These effects correlate with a decrease in the recruitment of H1 to the pluripotency genes OCT4 and NANOG during differentiation in the SETD7 knock down that might affect the proper silencing of these genes during differentiation. PMID- 26890255 TI - Organocatalytic, Asymmetric Total Synthesis of (-)-Haliclonin A. AB - The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone. PMID- 26890254 TI - Coherence between Rat Sensorimotor System and Hippocampus Is Enhanced during Tactile Discrimination. AB - Rhythms with time scales of multiple cycles per second permeate the mammalian brain, yet neuroscientists are not certain of their functional roles. One leading idea is that coherent oscillation between two brain regions facilitates the exchange of information between them. In rats, the hippocampus and the vibrissal sensorimotor system both are characterized by rhythmic oscillation in the theta range, 5-12 Hz. Previous work has been divided as to whether the two rhythms are independent or coherent. To resolve this question, we acquired three measures from rats--whisker motion, hippocampal local field potential (LFP), and barrel cortex unit firing--during a whisker-mediated texture discrimination task and during control conditions (not engaged in a whisker-mediated memory task). Compared to control conditions, the theta band of hippocampal LFP showed a marked increase in power as the rats approached and then palpated the texture. Phase synchronization between whisking and hippocampal LFP increased by almost 50% during approach and texture palpation. In addition, a greater proportion of barrel cortex neurons showed firing that was phase-locked to hippocampal theta while rats were engaged in the discrimination task. Consistent with a behavioral consequence of phase synchronization, the rats identified the texture more rapidly and with lower error likelihood on trials in which there was an increase in theta-whisking coherence at the moment of texture palpation. These results suggest that coherence between the whisking rhythm, barrel cortex firing, and hippocampal LFP is augmented selectively during epochs in which the rat collects sensory information and that such coherence enhances the efficiency of integration of stimulus information into memory and decision-making centers. PMID- 26890257 TI - STK38 at the crossroad between autophagy and apoptosis. AB - We describe the STK38 protein kinase as a conserved regulator of autophagy. We discovered STK38 as a novel binding partner of Beclin1, a key regulator of autophagy. By combining molecular, cell biological and genetic approaches, we show that STK38 promotes autophagosome formation in human cells and in Drosophila. Furthermore, we also provide evidence demonstrating that STK38 with the small GTPase RalB, assist the co-ordination between autophagic and apoptotic events upon autophagy induction, hence proposing a role for STK38 in determining cellular fate in response to autophagic conditions. PMID- 26890256 TI - Immunization coverage among splenectomized patients: Results of an ad hoc survey in Puglia Region (South of Italy). AB - Patients with anatomic or functional asplenia have a 10-50 times higher risk than general population to develop Overwhelming Post-Splenectomy Infection. Evidences are unanimous in recommending splenectomised patients to receive meningococcal, antipneumococcal and Haemophilus influenzae type B vaccinations according to a specific timing. In Italy there are no current data on the immunisation coverage in these patients. This study aims to investigate immunisation coverage in patients undergoing elective or urgent splenectomy for 2012-2013 in the 3 Apulian hospitals. The patients discharged with the code ICD-9-CM 41.5 - "Total splenectomy" were enrolled. The administration of vaccines was verified through consultation of medical records, archives of general practitioners and vaccination offices. In the study period, 166 subjects underwent splenectomy and none of them received vaccinations during hospitalization. 25 splenectomised patients (15.1%) received at least one of the recommended vaccinations. 21 patients (12.6%) received vaccine against Streptococcus pneumonia, 13 (7.8%) meningococcal vaccine, 10 patients (6%) Haemophilus influenzae type B vaccine. The low vaccination coverage could be due both to poor perception of the risk of infection and to a lack of knowledge on vaccinations by surgeons. For this reason it is necessary to draw up and share operational protocols that establish the administration of vaccines. PMID- 26890259 TI - Urinary bisphenol A concentrations positively associated with glycated hemoglobin and other indicators of diabetes in Canadian men. AB - BACKGROUND: Bisphenol A (BPA), an endocrine disrupting chemical (EDC), may pose a risk to human health, including diabetes. However, epidemiological studies from the U.S., China and South Korea showed inconsistent results. OBJECTIVE: To examine the associations between BPA and indicators of diabetes in the general Canadian population. METHODS: The analysis was based on cross-sectional data from the Canadian Health Measures Survey (CHMS) Cycle 2 (2009-2011). We included 1915 participants with glycated hemoglobin (HbA1c) measurement and 2405 participants with serum glucose (SG) measurement aged 3-79 years, respectively. Multiple linear regression analyses were performed to model HbA1c and log-transformed SG levels associated with quartiles of urinary BPA concentrations controlling for potential confounders. Further, in adults (age>=18 years), logistic regression analysis was conducted to evaluate the association between BPA and physician diagnosed diabetes mellitus (DM). Bootstrap weights were applied to all the analyses to account for the complex survey design. RESULTS: The geometric mean of urinary BPA was 1.21 (+/-0.05)ug/L. Overall, a positive association was observed between urinary BPA quartiles and HbA1c levels in men after controlling for potential confounders (P<0.05), but not in women and children. Similar patterns were found for the associations of BPA with log-transformed SG levels and doctor diagnosed DM. CONCLUSIONS: Higher urinary BPA levels were associated with adverse glucose homeostasis in Canadian men, independent of major covariates. Prospective studies with longitudinal design are needed to further investigate the causality. PMID- 26890258 TI - Thickness Mismatch of Coexisting Liquid Phases in Noncanonical Lipid Bilayers. AB - Lipid composition dictates membrane thickness, which in turn can influence membrane protein activity. Lipid composition also determines whether a membrane demixes into coexisting liquid-crystalline phases. Previous direct measurements of demixed lipid membranes have always found a liquid-ordered phase that is thicker than the liquid-disordered phase. Here we investigated noncanonical ternary lipid mixtures designed to produce bilayers with thicker disordered phases than ordered phases. The membranes were composed of short, saturated (ordered) lipids; long, unsaturated (disordered) lipids; and cholesterol. We found that few of these systems yield coexisting liquid phases above 10 degrees C. For membranes that do demix into two liquid phases, we measured the thickness mismatch between the phases by atomic force microscopy and found that not one of the systems yields thicker disordered than ordered phases under standard experimental conditions. We found no monotonic relationship between demixing temperatures of these ternary systems and either estimated thickness mismatches between the liquid phases or the physical parameters of single-component membranes composed of the individual lipids. These results highlight the robustness of a membrane's liquid-ordered phase to be thicker than the liquid disordered phase, regardless of the membrane's lipid composition. PMID- 26890263 TI - Hybridizing Poly(epsilon-caprolactone) and Plasmonic Titanium Nitride Nanoparticles for Broadband Photoresponsive Shape Memory Films. AB - Plasmonic nanoparticles can confine light in nanoscale and locally heat the surrounding. Here we use titanium nitride (TiN) nanoparticles as broadband plasmonic light absorbers and synthesized a highly photoresponsive hybrid cross linked polymer from shape memory polymer poly(epsilon-caprolactone) (PCL). The TiN-PCL hybrid is responsive to sunlight and the threshold irradiance was among the lowest when compared with other photoresponsive shape memory polymers studied previously. Sunlight heating with TiN NPs can be applied to other heat responsive smart polymers, thereby contributing to energy-saving smart polymers research for a sustainable society. PMID- 26890262 TI - Digit Sucking Habit and Association with Dental Caries and Oral Hygiene Status of Children Aged 6 Months to 12 Years Resident in Semi-Urban Nigeria. AB - OBJECTIVES: Non-nutritive sucking (NNS) is a common behavior in childhood. The association between digit sucking, dental caries and oral health has been studied with inconclusive results. The objectives of this study were to determine the prevalence of, and the association between digit sucking, caries and oral hygiene status of children age six months to 12 years, resident in Ile-Ife, Osun State, Nigeria. METHODS: A cross-sectional study was conducted in Ife Central Local Government Area of Osun State. Data were collected through a household survey using a multi-stage sampling procedure from children between six months and 12 years. Details of each child's socio-demographic characteristics, digit sucking habits, caries status and oral health status were collected. The association between digit sucking, caries status and oral hygiene status was determined using Chi square and Logistic regression. RESULTS: The mean age of the 992 study participants was 5.8 +/- (3.2) years. The prevalence of digit sucking, caries and poor oral hygiene were 7.2%, 10.5% and 2.4% respectively. The mean dmft score was 0.22 +/- (0.80), mean DMFT score was 0.04 +/- (0.30) while mean Oral Hygiene Index score was 1.27 +/- (0.73). Digit sucking increased the odds of having caries (OR: 1.28; CI: 0.58-2.81) but decreased the odds of having poor oral hygiene (OR: 0.58; CI: 0.34-1.01) insignificantly. CONCLUSIONS: Digit sucking was not a significant predictor of caries and oral hygiene status, although the odds of having caries increased while the odds of having poor oral hygiene decreased with digit sucking. PMID- 26890261 TI - Analysis of Osteoclastogenesis/Osteoblastogenesis on Nanotopographical Titania Surfaces. AB - A focus of orthopedic research is to improve osteointegration and outcomes of joint replacement. Material surface topography has been shown to alter cell adhesion, proliferation, and growth. The use of nanotopographical features to promote cell adhesion and bone formation is hoped to improve osteointegration and clinical outcomes. Use of block-copolymer self-assembled nanopatterns allows nanopillars to form via templated anodization with control over height and order, which has been shown to be of cellular importance. This project assesses the outcome of a human bone marrow-derived co-culture of adherent osteoprogenitors and osteoclast progenitors on polished titania and titania patterned with 15 nm nanopillars, fabricated by a block-copolymer templated anodization technique. Substrate implantation in rabbit femurs is performed to confirm the in vivo bone/implant integration. Quantitative and qualitative results demonstrate increased osteogenesis on the nanopillar substrate with scanning electron microscopy, histochemical staining, and real-time quantitative reverse transcription polymerase chain reaction analysis performed. Osteoblast/osteoclast co-culture analysis shows an increase in osteoblastogenesis-related gene expression and reduction in osteoclastogenesis. Supporting this in vitro finding, in vivo implantation of substrates in rabbit femora indicates increased implant/bone contact by ~20%. These favorable osteogenic characteristics demonstrate the potential of 15 nm titania nanopillars fabricated by the block copolymer templated anodization technique. PMID- 26890264 TI - Evaluation of Vascular Endothelial Growth Factor and Its Receptors in Human Neointima. AB - OBJECTIVE: The potential contribution of vascular endothelial growth factor (VEGF) in neointima development has been evaluated in numerous animal studies. However, its role remains controversial. Moreover, little is known about neointima formation in humans. In this study we assessed the expression of VEGF-A and its receptors in the human neointima formed within vascular anastomosis. METHODS: The studied material comprised neointima samples harvested during secondary vascular operations from patients with chronic limb ischemia after aorto-/iliofemoral bypass grafting who developed vascular graft occlusion at 6-18 months after the initial surgical treatment. The control material consisted of segments of femoral arteries without visible macroscopic lesions collected from organ donors. The expression and content of VEGF-A, VEGFR-1 and VEGFR-2 were analyzed with PCR and ELISA methods, respectively. RESULTS: We observed a significantly increased expression of VEGF-A and VEGFR-2 mRNA in neointima compared to the normal aorta. A significantly higher protein content of VEGF-A and VEGFR-2 in neointima samples compared to the controls was also observed. No significant difference of VEGFR-1 content and VEGFR-1 mRNA expression was found in the studied material. CONCLUSION: These results indicate a possible involvement of the VEGF-A and VEGFR-2 system in the pathologic process of human neointima formation after vascular interventions. PMID- 26890260 TI - SIRT1 Disruption in Human Fetal Hepatocytes Leads to Increased Accumulation of Glucose and Lipids. AB - There are unprecedented epidemics of obesity, such as type II diabetes and non alcoholic fatty liver diseases (NAFLD) in developed countries. A concerning percentage of American children are being affected by obesity and NAFLD. Studies have suggested that the maternal environment in utero might play a role in the development of these diseases later in life. In this study, we documented that inhibiting SIRT1 signaling in human fetal hepatocytes rapidly led to an increase in intracellular glucose and lipids levels. More importantly, both de novo lipogenesis and gluconeogenesis related genes were upregulated upon SIRT1 inhibition. The AKT/FOXO1 pathway, a major negative regulator of gluconeogenesis, was decreased in the human fetal hepatocytes inhibited for SIRT1, consistent with the higher level of gluconeogenesis. These results indicate that SIRT1 is an important regulator of lipid and carbohydrate metabolisms within human fetal hepatocytes, acting as an adaptive transcriptional response to environmental changes. PMID- 26890266 TI - Helical Oligoenes: Conformations, Bond Alternation, and Competing Through-Bond and Through-Space Transmission. AB - There is a consensus that long-range electron transfer/transport occurs by a through-bond rather than through-space mechanism. In helical all-Z, all-s-cis oligoenes, one can set up an interesting competition in the medium-separation regime between a closer (in distance) through-space path and a more distant through-bond one. Although such oligoene conformations/isomers are unstable (by around 4 kcal mol(-1) per double bond relative to all-E, all-s-trans isomers), recent synthetic efforts on truncated helicenes and oligothiophenes have provided related molecules. On the way to transmission calculations with electrodes attached to the termini of helical oligoenes, we uncover an interesting conformational ambiguity in all-Z, all-s-cis oligoenes, the existence of a broad conformational minimum for helical compression, with hints of end-to-end frontier orbital-caused stabilization. There is relationship between helical oligoene structures and the corresponding substructure of a helicene, but there are also significant differences in the number of olefin subunits per helix turn. In Huckel transport calculations, the role of TB or TS mechanisms is obscured to an extent by variations in bond alternation and dihedral angle along the oligomer chain. However, the operation of a dominant through bond mechanism emerges clearly in local transmission plots. In moving the electrodes to carbon position related by quantum interference, it is possible to uncover a through space mechanism. PMID- 26890265 TI - Matricellular Protein Periostin Mediates Intestinal Inflammation through the Activation of Nuclear Factor kappaB Signaling. AB - Periostin is a matricellular protein that interacts with various integrin molecules on the cell surface. Although periostin is expressed in inflamed colonic mucosa, its role in the regulation of intestinal inflammation remains unclear. We investigated the role of periostin in intestinal inflammation using Postn-deficient (Postn-/-) mice. Intestinal epithelial cells (IECs) were transfected by Postn small interfering RNAs. Periostin expression was determined in colon tissue samples from ulcerative colitis (UC) patients. Oral administration of dextran sulfate sodium (DSS) or rectal administration of trinitrobenzene sulfonic acid, induced severe colitis in wild-type mice, but not in Postn-/- mice. Administration of recombinant periostin induced colitis in Postn-/- mice. The periostin neutralizing-antibody ameliorated the severity of colitis in DSS-treated wild-type mice. Silencing of Postn inhibited inteleukin (IL)-8 mRNA expression and NF-kappaB DNA-binding activity in IECs. Tumor necrosis factor (TNF)-alpha upregulated mRNA expression of Postn in IECs, and recombinant periostin strongly enhanced IL-8 expression in combination with TNF-alpha, which was suppressed by an antibody against integrin alphav (CD51). Periostin and CD51 were expressed at significantly higher levels in UC patients than in controls. Periostin mediates intestinal inflammation through the activation of NF-kappaB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease. PMID- 26890268 TI - Quelling Inflammation with Ketosis and Steric Chemistry. PMID- 26890267 TI - Randomized controlled trial on preemptive analgesia for acute postoperative pain management in children. AB - BACKGROUND: Preemptive analgesia is an anti-nociceptive treatment that starts before surgery and prevents the establishment of central sensitization. Whether preemptive analgesia is more effective than conventional regimens for managing postoperative pain remains controversial. This study evaluated the efficacy of intravenous preemptive analgesia for acute postoperative pain control in pediatric patients. METHODS: In this prospective randomized controlled trial, 51 children aged 3-7 years, scheduled for corrective osteotomy were randomized into control (group C) or preemptive (group P) group. Both groups received standardized general anesthesia, including intravenous patient-controlled analgesia (IV-PCA) with fentanyl, which was started before skin incision in group P or 5 min thereafter in group C. IV-PCA data, pain scores using verbal rating scale (VRS) and Wong-Baker FACES((r)) pain rating scale (WBFS), emergence agitation score (EAS) using the Pediatric Anesthesia Emergence Delirium (PAED) scale, analgesic requirements, and complications were recorded. RESULTS: The primary outcome, pain score at postoperative 1 h, showed no difference between the groups. Both groups did not demonstrate emergence agitation (PAED cutoff value >= 12), although the EAS at admission to the postanesthetic care unit (PACU) was lower in group P than in group C (P = 0.002; mean difference 4.85, 95% CI 1.97-7.73). There were no differences in the delivered volume of IV-PCA, frequency of pushing the IV-PCA button, effective push attempts, VRS, WBFS, EAS at discharge from the PACU, additional analgesic requirements, and complications. CONCLUSION: Preemptive analgesia using IV-PCA with fentanyl showed no significant advantages for postoperative analgesia after corrective osteotomy in pediatric patients. PMID- 26890269 TI - The conservation of aquatic ecosystems of the Orinoco River basin. PMID- 26890270 TI - Dissecting the clinical outcome and cause of abnormalities of the corpus callosum. PMID- 26890271 TI - A metal-responsive interdigitated bilayer for selective quantification of mercury(ii) traces by surface plasmon resonance. AB - Reusable surface plasmon resonance chips allowing the quantitative and selective detection of mercury(ii) ions in water at the 0.01 nM level are reported. The surface-modified gold sensor consists of a rarefied self-assembled monolayer of octanethiol topped with a Langmuir-Blodgett monolayer of an amphiphilic and highly-specific chelator. The interdigitated architecture confers to the bilayer a high packing density, surface coverage, and binding-group accessibility. PMID- 26890273 TI - Potentially preventable prehospital deaths from motor vehicle collisions. AB - BACKGROUND: In 2011, about 30,000 people died in motor vehicle collisions (MVCs) in the United States. We sought to evaluate the causes of prehospital deaths related to MVCs and to assess whether these deaths were potentially preventable. METHODS: Miami-Dade Medical Examiner records for 2011 were reviewed for all prehospital deaths of occupants of 4-wheeled motor vehicle collisions. Injuries were categorized by affected organ and anatomic location of the body. Cases were reviewed by a panel of 2 trauma surgeons to determine cause of death and whether the death was potentially preventable. Time to death and hospital arrival times were determined using the Fatality Analysis Reporting System (FARS) data from 2002 to 2012, which allowed comparison of our local data to national prevalence estimates. RESULTS: Local data revealed that 39% of the 98 deaths reviewed were potentially preventable (PPD). Significantly more patients with PPD had neurotrauma as a cause of death compared to those with a nonpreventable death (NPD) (44.7% vs. 25.0%, P =.049). NPDs were significantly more likely to have combined neurotrauma and hemorrhage as cause of death compared to PPDs (45.0% vs. 10.5%, P <.001). NPDs were significantly more likely to have injuries to the chest, pelvis, or spine. NPDs also had significantly more injuries to the following organ systems: lung, cardiac, and vascular chest (all P <.05). In the nationally representative FARS data from 2002 to 2012, 30% of deaths occurred on scene and another 32% occurred within 1 h of injury. When comparing the 2011 FARS data for Miami-Dade to the remainder of the United States in that year, percentage of deaths when reported on scene (25 vs. 23%, respectively) and within 1 h of injury (35 vs. 32%, respectively) were similar. CONCLUSIONS: Nationally, FARS data demonstrated that two thirds of all MVC deaths occurred within 1 h of injury. Over a third of prehospital MVC deaths were potentially preventable in our local sample. By examining injury patterns in PPDs, targeted intervention may be initiated. PMID- 26890272 TI - Subclinical cardiovascular changes in pediatric solid organ transplant recipients: A systematic review and meta-analysis. AB - CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. cIMT, central pWV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta-analysis was to investigate the prevalence of subclinical CV changes, as measured by cIMT, pWV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE((r)) and EMBASE and conducted meta-analysis for studies that evaluated cIMT, central pWV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean cIMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02-0.07; p < 0.0001) with an estimated pooled prevalence of elevated cIMT of 56.0% (95% CI 17.0-95.0). The one study that assessed pWV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation. PMID- 26890274 TI - Corona Yank in Edged Cathode Particles for Li-Ion Batteries. AB - In a heuristic endeavor based on electrostatics-dynamics considerations, an attempt has been made to explain the significant enhancement (~20%) observed in initial capacity for the as-synthesized, sharp-edged cathode particles of lithium nickel manganese cobalt oxide, and lithium nickel manganese oxide cathode systems which are considered here as illustrative examples. Also, the impressive capacity retention (~90%) observed for the milled blend of these, comprising smooth surfaced particles with cells made using respective cathode particles, has been explained. Enhancement in initial capacity observed for the edged particles can be squarely attributed to a corona-gain process. On the contrary, impressive capacity retention possible for the milled blend (of near-spherical particles) can be rationalized in terms of the absence of predominant energy drain encountered while shuttling charges across edges of the as-synthesized cathode particles, a process described as corona yank. PMID- 26890275 TI - In vitro Developmental Competence of Adult Sheep Oocytes Treated with Roscovitine. AB - The efficiency of in vitro sheep embryo production is still low compared to that observed in vivo and in other species. In this context, meiotic inhibition strategies emerged as a promising alternative to improve this biotechnology. So, this study aimed to evaluate, for the first time, the effects of roscovitine on in vitro maturation of sheep oocytes and their subsequent embryo development. For this, cumulus-oocyte complexes (COCs) were cultured for 6 h in the presence (Rosco) or absence (Control) of 75 MUm roscovitine and, subsequently, in vitro matured (IVM) for 18 h with gonadotropins. At 0 (Immature), 6 and 24 h of culture, the nuclear status of oocytes was evaluated by Hoechst staining. Embryo cleavage and blastocyst formation were recorded 30 h after in vitro fertilization and on day 7 of culture, respectively. Blastocyst quality was evaluated by differential staining. At 6 h, the GV rate in the Rosco treatment (93.8%) was similar to that observed in the Immature oocytes (94.9%) and significantly higher compared to Control (41.3%). After IVM for 18 h, a high and similar proportion of oocytes from Rosco (93.6%) and Control (88.4%) reached the MII stage. In both treatments, approximately 70% of oocytes cleaved and 50% of them developed up to blastocyst. The mean percentage of blastocyst cells, embryoblast, trophoblast and pyknosis did also not differ between Control and Rosco. In conclusion, roscovitine, at the studied experimental conditions, was efficient to reversibly inhibit the meiosis of adult sheep oocytes without detrimental effect on development and quality of the in vitro produced embryos. PMID- 26890276 TI - Efficiencies of thermodynamics when temperature-dependent energy levels exist. AB - Based on a generalized form of the second law of thermodynamics, in which the temperature-dependent energy levels of a system are appropriately included in entropy generation, we show that the effect reasonably appears in efficiencies of thermodynamic processes. PMID- 26890277 TI - A comparison of magnetic resonance imaging and ultrasonography (MRI/US)-fusion guided prostate biopsy devices: too many uncontrolled variables. PMID- 26890280 TI - A Quantitative Summary of The Listening Program (TLP) Efficacy Studies: What Areas Were Found to Improve by TLP Intervention? AB - A quantitative summary of existing research examining the effects of The Listening Program (TLP) on various functions in children is presented. Nine studies were used, looking at TLP intervention effects across studies, within each study and for various outcome measures. The studies looked at TLP intervention on children with autism spectrum disorder, Down syndrome, learning disabilities, auditory processing disorders, attention deficit hyperactivity disorders, Rhett syndrome, dyspraxia, cerebral palsy, fibromyalgia, arthritis and stroke. The magnitude of the TLP effect size revealed a mean value of 0.41 across all studies. For each individual study, effect size ranged from 0.23 to 1.28. Two studies yielded significantly larger effect size than the other studies. One of these studies (effect size 1.19) examined the improvement in auditory processing for children identified with autism. The other study (effect size 1.28) examined improvement in academically related skills of underachieving school children. Larger effect sizes were obtained for research that examined auditory processing/listening skills (mean effect size 0.72) than for research looking at non-auditory areas (mean effect size 0.31), although all revealed positive changes. The effect size of various outcome measures is discussed in order to identify variables that might affect the outcomes as well as what these results mean to occupational therapists who would consider TLP intervention for clients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890278 TI - Amiloride Analogs as ASIC1a Inhibitors. AB - BACKGROUND: ASIC1a, the predominant acid-sensing ion channels (ASICs), is implicated in neurological disorders including stroke, traumatic spinal cord injury, and ALS. Potent ASIC1a inhibitors should have promising therapeutic potential for ASIC1a-related diseases. AIMS: We examined the inhibitory effects of a number of amiloride analogs on ASIC1a currents, aimed at understanding the structure-activity relationship and identifying potent ASIC1a inhibitors for stroke intervention. METHODS: Whole-cell patch-clamp techniques and a mouse model of middle cerebral artery occlusion (MCAO)-induced focal ischemia were used. Surflex-Dock was used to dock the analogs into the pocket with default parameters. RESULTS: Amiloride and its analogs inhibit ASIC1a currents expressed in Chinese hamster ovary cells with a potency rank order of benzamil > phenamil > 5-(N,N-dimethyl)amiloride (DMA) > amiloride > 5-(N,N-hexamethylene)amiloride (HMA) >= 5-(N-methyl-N-isopropyl)amiloride (MIA) > 5-(N-ethyl-N isopropyl)amiloride (EIPA). In addition, amiloride and its analogs inhibit ASIC currents in cortical neurons with the same potency rank order. In mice, benzamil and EIPA decreased MCAO-induced infarct volume. Similar to its effect on the ASIC current, benzamil showed a much higher potency than EIPA. CONCLUSION: Addition of a benzyl group to the terminal guanidinyl group resulted in enhanced inhibitory activity on ASIC1a. On the other hand, the bulky groups added to the 5-amino residues slightly decreased the activity. Among the tested amiloride analogs, benzamil is the most potent ASIC1a inhibitor. PMID- 26890279 TI - Predonation finger lancet punctures: a potential risk factor for interdonor pathogen transmission in the blood donor clinic. AB - BACKGROUND AND OBJECTIVES: Point-of-care testing using capillary blood from a finger prick is widely used for predonation haemoglobin testing of blood donors. It is common practice to cover the finger prick with a cotton swab and to instruct the donor to press for few minutes. The finger prick can cause blood contamination of surfaces in contact with the lanced finger, especially door handles, risking infectious disease transmission, particularly if another person touching the contaminated door handle also has a punctured fingertip. MATERIALS AND METHODS: First, we investigated contamination by blood (benzidine assay) of the door handles of our blood donor clinic, taking 175 samples 3 h after opening of the donation centre (baseline). We then introduced band-aids to cover the finger prick and started an information campaign using educational flyers to sensitize blood donors and staff to this problem (period-1). Thereafter, the staff was instructed to use the non-dominant hand for blood sampling and mandated to replace any discarded band-aids immediately (period-2). RESULTS: At baseline, 82% of the nurse room door handles showed contamination with blood. This decreased somewhat (10-40%) after period-1, but only after immediate mandatory band-aid replacement on any donor finger without a band-aid (period-2), no further blood contaminations were detected. CONCLUSION: Blood contamination of shared surfaces can occur after finger prick for capillary blood sampling. Application of a band-aid and use of the non-dominant hand for fingertip incision are easy to apply and effective in reducing this iatrogenic health hazard. PMID- 26890282 TI - Endoscopic double stenting for afferent and efferent loop stenosis in a patient with recurrent gastric carcinoma after Billroth II reconstruction. PMID- 26890281 TI - Transformation of Probiotic Yeast and Their Recovery from Gastrointestinal Immune Tissues Following Oral Gavage in Mice. AB - Development of recombinant oral therapy would allow for more direct targeting of the mucosal immune system and improve the ability to combat gastrointestinal disorders. Adapting probiotic yeast in particular for this approach carries several advantages. These strains have not only the potential to synthesize a wide variety of complex heterologous proteins but are also capable of surviving and protecting those proteins during transit through the intestine. Critically, however, this approach requires expertise in many diverse laboratory techniques not typically used in tandem. Furthermore, although individual protocols for yeast transformation are well characterized for commonly used laboratory strains, emphasis is placed here on alternative approaches and the importance of optimizing transformation for less well characterized probiotic strains. Detailing these methods will help facilitate discussion as to the best approaches for testing probiotic yeast as oral drug delivery vehicles and indeed serve to advance the development of this novel strategy for gastrointestinal therapy. PMID- 26890284 TI - A Successful Strategy to Reduce Loss to Follow-Up in HIV Outpatient Care: Experiences of a Large Urban Clinic in the United Kingdom. PMID- 26890283 TI - Population-Based Estimates of Life Expectancy After HIV Diagnosis: United States 2008-2011. AB - INTRODUCTION: Using National HIV surveillance system data, we estimated life expectancy and average years of life lost (AYLL) among persons diagnosed with HIV infection during 2008-2011. METHODS: Population-based surveillance data, restricted to persons with diagnosed HIV infection aged 13 years or older, from all 50 states and Washington, D.C. were used to estimate life expectancy after HIV diagnosis using the life table method. Generated estimates were compared with life expectancy in the general population in the same calendar year to calculate AYLL. Life expectancy and AYLL were also estimated for subgroups by age, sex, and race/ethnicity. RESULTS: The overall life expectancy after HIV diagnosis in the United States increased by 3.43 years from 25.43 (95% CI: 25.37 to 25.49) in 2008 to 28.86 (95% CI: 28.80 to 28.92) in 2011. Improvements were observed irrespective of sex, race/ethnicity, transmission category, and stage of disease at diagnosis, though the extent of improvement varied by different characteristics. Based on the life expectancy in the general population, in 2010, the AYLL were 12.8 years for males and 16.5 years for females. By race/ethnicity, on average, blacks (13.3 years) and whites (13.4 years) had fewer AYLL than Hispanics/Latinos (14.7). CONCLUSIONS: Despite improvements in life expectancy among people diagnosed with an HIV infection during 2008-2011, disparities by sex and by race/ethnicity persist. Targeted efforts should continue to further reduce disparities and improve life expectancy after HIV diagnosis. PMID- 26890286 TI - Selective Dinitrogen Conversion to Ammonia Using Water and Visible Light through Plasmon-induced Charge Separation. AB - The generation of ammonia from atmospheric nitrogen and water using sunlight is a preferable approach to obtaining ammonia as an energy carrier and potentially represents a new paradigm for achieving a low-carbon and sustainable-energy society. Herein, we report the selective conversion of dinitrogen into ammonia through plasmon-induced charge separation by using a strontium titanate (SrTiO3) photoelectrode loaded with gold nanoparticles (Au-NPs) and a zirconium/zirconium oxide (Zr/ZrOx ) thin film. We observed the simultaneous stoichiometric production of ammonia and oxygen from nitrogen and water under visible-light irradiation. PMID- 26890285 TI - Culex pipiens and Stegomyia albopicta (= Aedes albopictus) populations as vectors for lineage 1 and 2 West Nile virus in Europe. AB - The emerging disease West Nile fever is caused by West Nile virus (WNV), one of the most widespread arboviruses. This study represents the first test of the vectorial competence of European Culex pipiens Linnaeus 1758 and Stegomyia albopicta (= Aedes albopictus) (both: Diptera: Culicidae) populations for lineage 1 and 2 WNV isolated in Europe. Culex pipiens and S. albopicta populations were susceptible to WNV infection, had disseminated infection, and were capable of transmitting both WNV lineages. This is the first WNV competence assay to maintain mosquito specimens under environmental conditions mimicking the field (day/night) conditions associated with the period of maximum expected WNV activity. The importance of environmental conditions is discussed and the issue of how previous experiments conducted in fixed high temperatures may have overestimated WNV vector competence results with respect to natural environmental conditions is analysed. The information presented should be useful to policymakers and public health authorities for establishing effective WNV surveillance and vector control programmes. This would improve preparedness to prevent future outbreaks. PMID- 26890287 TI - Enhancing Decision Support for Vector-Borne Disease Control Programs--The Disease Data Management System. PMID- 26890288 TI - Binge eating and emotional eating behaviors among adolescents and young adults with bipolar disorder. AB - BACKGROUND: This study investigates nutritional behavior among adolescents and young adults with bipolar disorder (BP) in comparison to those without history of major psychiatric disorder. METHODS: 131 participants (82 BP, 49 controls) with a mean age of 16.11 +/- 1.61 years were included. The self-reported Quick Weight, Activity, Variety & Excess (WAVE) Screener was used to assess dietary habits, yielding a total nutritional score as well as Excess, Variety, and Household Food Insecurity subscale scores. Specifically, the Variety subscale was used to measure daily consumption of essential nutrients; the Excess subscale measured unhealthy eating behaviors such as binge eating and excessive intake of fat and sugar; and the Household Food Insecurity subscale was used to detect food insecurity. Within-group analysis was conducted on participants with BP to identify correlates of unhealthy diet. RESULTS: BP participants scored significantly lower than controls on the WAVE (t=2.62, p=0.010), specifically the Excess subscale (t=3.26, p=0.001). This was related to higher prevalence of binge eating and emotional eating behaviors among participants with BP compared to controls. Within-group analyses showed that self-reported emotional dysregulation/impulsivity was associated with maladaptive nutritional behaviors (t=3.38, p=0.035). LIMITATIONS: Cross-sectional design. Within-group analyses were underpowered. Diet quality was measured using a brief self-report screener. CONCLUSION: Adolescents and young adults with BP have poorer nutritional behaviors compared to controls, and this difference is related to stress-induced eating. This demonstrates the need to screen for stress-induced eating and to intervene when needed in order to optimize nutritional behaviors among adolescents and young adults with BP. PMID- 26890289 TI - Impact of diagnosed depression on healthcare costs in adults with and without diabetes: United States, 2004-2011. AB - OBJECTIVE: This study used the Medical Expenditures Panel Survey (MEPS) to estimate the cost of diabetes, depression, and comorbid diabetes and depression over 8 years. METHODS: An 8-year pooled dataset was created using the household and medical provider components of MEPS. Medical expenditures were adjusted to a common 2014 dollar value. Analyses used responses of 147,095 individuals >=18 years of age for the years 2004-2011. The dependent variable in this study was total healthcare expenditure and the primary independent variables were diabetes and depression status. A two-part (probit/GLM) model was used to estimate the annual medical spending and marginal effects were calculated for incremental cost. RESULTS: In the pooled sample, after adjusting for socio-demographic factors, comorbidities and time trend covariates, the incremental cost of depression only was $2654 (95% CI 2343-2966), diabetes was $2692 (95% CI 2338 3046), and both was $6037 (CI 95% 5243-6830) when compared to patients with none. Based on the unadjusted mean, annual average aggregate cost of depression only was estimated at $238.3 billion, diabetes only $150.1 billion and depression and diabetes together was $77.6 billion. CONCLUSION: Costs at both the individual and aggregate level are significant, with comorbid diagnoses resulting in higher incremental costs than the sum of the costs for each diagnosis alone. In addition, while the cost of depression increased over time, the cost of diabetes decreased over time, much due to decreased inpatient costs. This study highlights the tremendous cost savings possible through more aggressive screening, diagnosis, and treatment of depression. PMID- 26890290 TI - Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes. AB - A bidirectional relationship seems to exist between diabetes mellitus and development of pancreatic tumors. Metformin, the most widely used drug in the treatment of Type 2 diabetes mellitus, has recently emerged as a potentially active agent in cancer chemoprevention and treatment. In this article, we discuss the potential correlation between glycemic status, administration of antiglycemic treatments, such as metformin or insulin, and prognosis of pancreatic neuroendocrine tumors patients treated with everolimus and octreotide, on the basis of existing evidence and our experience. PMID- 26890291 TI - Association between Severity of MERS-CoV Infection and Incubation Period. AB - We analyzed data for 170 patients in South Korea who had laboratory-confirmed infection with Middle East respiratory syndrome coronavirus. A longer incubation period was associated with a reduction in the risk for death (adjusted odds ratio/1-day increase in incubation period 0.83, 95% credibility interval 0.68 1.03). PMID- 26890292 TI - Combination of adjuvant chemotherapy and radiotherapy is associated with improved survival at early stage type II endometrial cancer and carcinosarcoma. AB - AIMS: The aim of this study was to describe the impact of postoperative adjuvant treatment modalities and identify risk factors associated with recurrence and survival rates in women diagnosed with early stage type II endometrial cancer and carcinosarcoma. METHODS: In this retrospective study, patients diagnosed with early stage (stages I-II) carcinosarcoma and type II endometrial cancer were reviewed. All women underwent comprehensive surgical staging. Postoperative treatment options of chemotherapy (CT), radiotherapy (RT), observation (OBS) and chemotherapy-radiotherapy (CT-RT) combination were compared in terms of recurrence and survival outcome. RESULTS: In CT-RT treatment arm, recurrence rate was found as 12.5% and this result is significantly lower than the other treatment approaches (P = 0.01 CT alone: 33.3%, RT alone: 26.7%, OBS: 62.5%). Three-year disease free survival(DFS) rate and overall survival (OS) rate were statistically higher for the group of women treated with combination of CT-RT (92 95%) compared to the women treated with RT alone (65-72%), treated with CT alone (67-74%) and women who received no adjuvant therapy (38-45%). The multivariate analysis revealed that carcinosarcoma histology was associated with shortened DFS and OS (P = 0.001, P = 0.002). On the other hand, being at stage Ia (P = 0.01, P = 0.04) and receiving adjuvant treatment of CT-RT combination (P = 0.005, P = 0.002) appeared to lead to increased DFS and OS rates. CONCLUSIONS: We identified that a combination treatment of chemotherapy and radiotherapy is superior compared to other postoperative adjuvant treatment approaches concerning PFS, OS and recurrence rates in stages I-II of type II endometrial cancers and uterine carcinosarcoma. PMID- 26890293 TI - Short-Term and Long-Term Reproducibility of Hypertension Phenotypes Obtained by Office and Ambulatory Blood Pressure Measurements. AB - The authors aimed to assess the reproducibility of normotension and white-coat, masked, and sustained hypertension in 839 untreated patients who underwent two separate assessments (median, 3; interquartile range, 0-13 months) by both office and ambulatory blood pressure (BP) monitoring (ABPM). The proportion of patients falling into the same category in the two assessments was: 52% normotension and 55% white-coat, 47% masked, and 82% sustained hypertension. The most frequent switch was to sustained hypertension (26% of white-coat and 33% of masked hypertension). No clinical factors predicted the change in category, except for higher office diastolic BP in patients with masked hypertension who developed sustained hypertension, compared with those who remained with masked hypertension (84+/-4 mm Hg vs 80+/-5 mm Hg; P=.006). The reproducibility of hypertension phenotypes was highly dependent on the time between assessments. The authors conclude that white-coat and masked hypertension phenotypes are only reproducible in the short-term, while they frequently shift towards sustained hypertension in the long-term. PMID- 26890294 TI - Cervical Spine pain as a presenting complaint in metastatic pancreatic cancer: a case report. AB - A 48 year-old female presented to her primary care physician with a two-month history of neck pain with negative cervical spine x-rays. During that office visit, the patient was noted to be tachycardic with EKG revealing ST depressions, which led to hospital admission. Acute coronary syndrome was ruled out, however, persistent neck pain warranted inpatient MRI of the cervical spine, which revealed a cervical spine lesion. Extensive investigation and biopsy ultimately confirmed stage IV pancreatic adenocarcinoma with metastases to the bone, liver, and likely lung. In the literature, the findings of a primary metastatic site being bone is rare with only a few case reports showing vertebral or sternal metastasis as the first clinical manifestation of pancreatic cancer. The uniqueness of this case lies in the only presenting complaint being cervical spine pain in the setting of extensive metastases to the liver, bone, and likely lung. PMID- 26890295 TI - h-index or G-spot: Female nursing researchers' conditions for an academic career. PMID- 26890296 TI - Evaluation and Monitoring of a Child With Hydrocarbon Pneumonitis Using Point-of Care Lung Ultrasound in the Pediatric Emergency Department. AB - A well-appearing 3-year-old boy presented to the pediatric emergency department 2 hours after a presumed hydrocarbon ingestion. He was referred to the emergency department by his pediatrician after consultation with the local poison control center after possibly ingesting ylang ylang (Cananga odorata) fragrance oil. The child was asymptomatic with a normal physical examination. Point-of-care lung ultrasound identified focal hydrocarbon pneumonitis in the right lung and demonstrated resolution of these findings. Utilization of point-of-care ultrasound resulted in a shorter emergency department length of stay and the avoidance of radiation exposure from serial chest x-rays. PMID- 26890297 TI - Point-of-Care Ultrasonography for the Rapid Diagnosis of Intussusception: A Case Series. AB - We present a case series describing an infant and a child who presented with abdominal discomfort and their conditions were diagnosed with intussusception by point-of-care ultrasound. These cases illustrate how point-of-care ultrasound led to the expeditious diagnosis of intussusception. PMID- 26890298 TI - Neonatal Gallstones Serendipitously Discovered by Point-of-Care Ultrasound in the Pediatric Emergency Department. AB - Cholelithiasis in children was once thought to be uncommon, but the prevalence has increased in recent years. We present a case of a 3-month-old infant brought to the pediatric emergency department for vomiting and increased fussiness. A point-of-care ultrasound was performed to rule out pyloric stenosis but revealed multiple stones within the gallbladder. Ultrasound findings and a review of technique for ultrasound of the gallbladder are presented. PMID- 26890299 TI - Point-of-Care Ultrasound Diagnosis of Bilateral Retinal Detachment Associated With Vogt-Koyanagi-Harada Disease in the Pediatric Emergency Department. AB - We report a case of a 16-year-old girl with acute visual complaints who was diagnosed with bilateral retinal detachment using point-of-case ultrasound and ultimately was diagnosed with Vogt-Koyanagi-Harada disease. This case illustrates the use of point-of-care ultrasound by the pediatric emergency physician to recognize the ocular abnormality associated with this rare disease. PMID- 26890300 TI - James William Osborne, PhD 1928-2015. PMID- 26890301 TI - Errata. PMID- 26890302 TI - Regulation of BMP2-induced intracellular calcium increases in osteoblasts. AB - Although bone morphogenetic protein-2 (BMP2) is a well-characterized regulator that stimulates osteoblast differentiation, little is known about how it regulates intracellular Ca2+ signaling. In this study, intracellular Ca2+ concentration ([Ca2+ ]i ) upon BMP2 application, focal adhesion kinase (FAK) and Src activities were measured in the MC3T3-E1 osteoblast cell line using fluorescence resonance energy transfer-based biosensors. Increase in [Ca2+ ]i , FAK, and Src activities were observed during BMP2 stimulation. The removal of extracellular calcium, the application of membrane channel inhibitors streptomycin or nifedipine, the FAK inhibitor PF-573228 (PF228), and the alkaline phosphatase (ALP) siRNA all blocked the BMP2-stimulated [Ca2+ ]i increase, while the Src inhibitor PP1 did not. In contrast, a gentle decrease of endoplasmic reticulum calcium concentration was found after BMP2 stimulation, which could be blocked by both streptomycin and PP1. Further experiments revealed that BMP2 induced FAK activation could not be inhibited by PP1, ALP siRNA or the calcium channel inhibitor nifedipine. PF228, but not PP1 or calcium channel inhibitors, suppressed ALP elevation resulting from BMP2 stimulation. Therefore, our results suggest that BMP2 can increase [Ca2+ ]i through extracellular calcium influx regulated by FAK and ALP and can deplete ER calcium through Src signaling simultaneously. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1725-1733, 2016. PMID- 26890303 TI - New and old agents in the management of diabetic nephropathy. AB - PURPOSE OF REVIEW: Diabetic nephropathy is a long-standing complication of diabetes mellitus and is responsible for more than 40% of end-stage renal disease cases in developed countries. Unfortunately, conventional renin-angiotensin aldosterone system (RAAS) inhibitor medications only partially protect against the development and progression of diabetic nephropathy. Moreover, RAAS inhibitors have failed as primary prevention therapy in type 1 diabetes. Thus, agents targeting alternative pathogenic mechanisms leading to diabetic nephropathy have been intensively investigated, which is the topic of this review. RECENT FINDINGS: Promising emerging agents have targeted neurohormonal activation (alternative components of the RAAS and neprilysin inhibition), tubuloglomerular feedback mechanisms (sodium glucose cotransporter 2 inhibition and incretin-based therapy) and renal inflammation/fibrosis. SUMMARY: Evidence demonstrating the potential of these agents to protect and prevent progression of diabetic nephropathy is summarized in this review. There are dedicated clinical trials ongoing with these therapies, which have the potential to change the clinical practice. PMID- 26890305 TI - Underestimation of Invasive Meningococcal Disease in Italy. AB - Knowing the incidence of invasive meningococcal disease (IMD) is essential for planning appropriate vaccination policies. However, IMD may be underestimated because of misdiagnosis or insufficiently sensitive laboratory methods. Using a national molecular surveillance register, we assessed the number of cases misdiagnosed and diagnoses obtained postmortem with real-time PCR (rPCR), and we compared sensitivity of rPCR versus culture-based testing. A total of 222 IMD cases were identified: 11 (42%) of 26 fatal cases had been misdiagnosed or undiagnosed and were reclassified as IMD after rPCR showed meningococcal DNA in all available specimens taken postmortem. Of the samples tested with both rPCR and culture, 58% were diagnosed by using rPCR alone. The underestimation factor associated with the use of culture alone was 3.28. In countries such as Italy, where rPCR is in limited use, IMD incidence may be largely underestimated; thus, assessments of benefits of meningococcal vaccination may be prone to error. PMID- 26890304 TI - Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer. AB - To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS >=7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of lower methylation in the recurrence group (n=30) than in the no-recurrence (n=52) group. We conclude that whole-genome methylation profiling with CHARM revealed distinct patterns of differential DNA methylation between normal prostate and PCa tissues, as well as between different risk groups of PCa as defined by Gleason scores. A panel of selected DMRs may serve as novel surrogate biomarkers for Gleason score in PCa. PMID- 26890306 TI - Modeling level-of-safety for bus stops in China. AB - OBJECTIVE: Safety performance at bus stops is generally evaluated by using historical traffic crash data or traffic conflict data. However, in China, it is quite difficult to obtain such data mainly due to the lack of traffic data management and organizational issues. In light of this, the primary objective of this study is to develop a quantitative approach to evaluate bus stop safety performance. METHODS: The concept of level-of-safety for bus stops is introduced and corresponding models are proposed to quantify safety levels, which consider conflict points, traffic factors, geometric characteristics, traffic signs and markings, pavement conditions, and lighting conditions. Principal component analysis and k-means clustering methods were used to model and quantify safety levels for bus stops. RESULTS: A case study was conducted to show the applicability of the proposed model with data collected from 46 samples for the 7 most common types of bus stops in China, using 32 of the samples for modeling and 14 samples for illustration. Based on the case study, 6 levels of safety for bus stops were defined. Finally, a linear regression analysis between safety levels and the number of traffic conflicts showed that they had a strong relationship (R(2) value of 0.908). CONCLUSIONS: The results indicated that the method was well validated and could be practically used for the analysis and evaluation of bus stop safety in China. The proposed model was relatively easy to implement without the requirement of traffic crash data and/or traffic conflict data. In addition, with the proposed method, it was feasible to evaluate countermeasures to improve bus stop safety (e.g., exclusive bus lanes). PMID- 26890307 TI - Selecting Optimal Random Forest Predictive Models: A Case Study on Predicting the Spatial Distribution of Seabed Hardness. AB - Spatially continuous predictions of seabed hardness are important baseline environmental information for sustainable management of Australia's marine jurisdiction. Seabed hardness is often inferred from multibeam backscatter data with unknown accuracy and can be inferred from underwater video footage at limited locations. In this study, we classified the seabed into four classes based on two new seabed hardness classification schemes (i.e., hard90 and hard70). We developed optimal predictive models to predict seabed hardness using random forest (RF) based on the point data of hardness classes and spatially continuous multibeam data. Five feature selection (FS) methods that are variable importance (VI), averaged variable importance (AVI), knowledge informed AVI (KIAVI), Boruta and regularized RF (RRF) were tested based on predictive accuracy. Effects of highly correlated, important and unimportant predictors on the accuracy of RF predictive models were examined. Finally, spatial predictions generated using the most accurate models were visually examined and analysed. This study confirmed that: 1) hard90 and hard70 are effective seabed hardness classification schemes; 2) seabed hardness of four classes can be predicted with a high degree of accuracy; 3) the typical approach used to pre-select predictive variables by excluding highly correlated variables needs to be re-examined; 4) the identification of the important and unimportant predictors provides useful guidelines for further improving predictive models; 5) FS methods select the most accurate predictive model(s) instead of the most parsimonious ones, and AVI and Boruta are recommended for future studies; and 6) RF is an effective modelling method with high predictive accuracy for multi-level categorical data and can be applied to 'small p and large n' problems in environmental sciences. Additionally, automated computational programs for AVI need to be developed to increase its computational efficiency and caution should be taken when applying filter FS methods in selecting predictive models. PMID- 26890309 TI - Synthesis of graphitic ordered mesoporous carbon with cubic symmetry and its application in lithium-sulfur batteries. AB - The lithium-sulfur (Li-S) battery faces a couple of major problems in practical applications, including the low conductivity of sulfur and the dissolution of polysulfides. A cathode constructed using a composite of sulfur and ordered mesoporous carbon (OMC) is a promising solution to both problems, as OMCs can have high conductivity and a complex pore structure to trap polysulfides. In this work, we demonstrate that performance of the Li-S battery can be significantly enhanced by using an OMC with a high degree of graphitization and a pore network with cubic symmetry. This graphitic OMC (GOMC) can be produced in a single step using iron phthalocyanine precursor and a silica template with cubic Ia3d symmetry. The GOMC-sulfur (GOMC/S) composite is 175% higher in electrical conductivity compared to the typical OMC-sulfur (OMC/S) composite. In addition, the three-dimensional pore network in GOMC prevents the migration of dissolved polysulfides. These characteristics of GOMC contribute to the improved rate capability and cyclability of the corresponding Li-S battery. PMID- 26890308 TI - Heterozygous PTCH1 Mutations Impact the Bone Metabolism in Patients With Nevoid Basal Cell Carcinoma Syndrome Likely by Regulating SPARC Expression. AB - Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by bone and skin abnormalities and a predisposition to various tumors. Keratocystic odontogenic tumors (KCOTs), which are common tumors of the jaw that cause extensive damage to the jawbone, are usually accompanied with NBCCS. Germline PTCH1 mutations in NBCCS tumorigenesis have been frequently studied; however, little is known regarding the pathogenesis of bone abnormalities in this disease. This study sought to investigate the mechanism underlying heterozygous PTCH1 mutation-mediated abnormal bone metabolism in patients with NBCCS. Stromal cells were isolated from the fibrous capsules of patients with NBCCS-associated or non-syndromic keratocystic odontogenic tumors and non-syndromic tumor stromal cells without PTCH1 mutations served as controls. Germline PTCH1 heterozygous mutations were confirmed in all NBCCS samples and differential protein expression was identified using tandem mass tag-labeled proteomics analysis. Our findings revealed that osteonectin/SPARC expression was significantly downregulated in syndromic stromal cells compared with non syndromic stromal cells. SPARC expression was even lower in stromal cells carrying PTCH1 protein truncation mutations. PTCH1 siRNA transfection demonstrated that SPARC downregulation correlates with decreased PTCH1 expression. Furthermore, exogenous SPARC promoted osteogenic differentiation of syndromic stromal cells with enhanced development of calcium nodules. In addition, bone mineral density tests showed that patients with NBCCS exhibit weak bone mass compared with sex- and age-matched controls. This study indicates that germline PTCH1 heterozygous mutations play a major role in bone metabolism in patients with NBCCS, in particular in those with PTCH1 protein truncation mutations. SPARC may represent an important downstream modulator of PTCH1 mediation of bone metabolism. Thus, bone mineral density monitoring is critical for patients with NBCCS for prevention of osteoporosis. In addition, surgical procedures on syndromic-associated KCOTs should be performed with consideration of the weaker bone mass in such patients. (c) 2016 American Society for Bone and Mineral Research. PMID- 26890311 TI - Tuning polymer-surface chemistries and interfacial interactions with UV irradiated polystyrene chains to control domain orientations in thin films of PS b-PMMA. AB - We demonstrate a simple, rapid, cost-effective and robust approach to modify the surface of a solid substrate, based on a UV-irradiated film of a general plastic polymer. Thin films of homopolymer polystyrene (PS) of controlled thickness were spin-coated on diverse metal, semiconductor and polymeric surfaces. Specific surface chemistry was tuned with UV irradiation in air (UVIA); interactions at the PS/substrate interface were enhanced with UV irradiation in nitrogen (UVIN). Oxidized and cross-linked PS served as a neutral surface on various metal, quartz, semiconductor and polymeric substrates to induce perpendicularly oriented cylinders or lamellae in a self-assembled block copolymer. PMID- 26890310 TI - Mycobacterium orygis-Associated Tuberculosis in Free-Ranging Rhinoceros, Nepal, 2015. PMID- 26890313 TI - Dysfunctional autophagy is a driver of muscle stem cell functional decline with aging. AB - Regeneration of skeletal muscle relies on its resident stem cells, also known as satellite cells, which are normally quiescent. With aging, satellite cell quiescence is lost concomitant with a muscle regenerative decline. Here we demonstrate that autophagy sustains quiescence over time and that its failure with age drives senescence, which accounts for stem cell loss of function. Pharmacological and genetic reestablishment of autophagy restores homeostasis and regenerative functions in geriatric satellite cells, which has relevance for the elderly population. PMID- 26890312 TI - Pharmacological considerations in the use of stiripentol for the treatment of epilepsy. AB - INTRODUCTION: Despite the fact that more than 20 antiepileptic drugs (AEDs) are currently available, about one-third of patients still present drug resistance. Further efforts are required to develop novel and more efficacious therapeutic strategies, especially for refractory epileptic syndromes showing few and anecdotic therapeutic options. AREAS COVERED: Stiripentol (STP) is a second generation AED that shows GABAergic activity, with immature brain selectivity, and an indirect metabolic action on co-administered AEDs. Two pivotal studies demonstrated STP efficacy in patients with Dravet syndrome with refractory partial seizures, and marketing authorization in Europe, Canada and Japan was granted thereafter. Post-marketing surveys reported a good efficacy and tolerability profile. In addition, interesting data is currently emerging regarding off-label experimentation of STP in other forms of epilepsy. EXPERT OPINION: STP is an important addition to the limited treatment options available for patients resistant to common AEDs. The possibility to inhibit seizures through the metabolic pathway of lactate dehydrogenase and the inhibitory effects on the entry of Na(+) and Ca(2+) are the most recent findings to emerge about STP and could be proof of its neuroprotective action. Moreover, its positive effects on cognitive function, its good safety and tolerability profile and the increasing data about STP efficacy on other refractory epileptic syndromes may prove to be fertile grounds for further investigation. PMID- 26890314 TI - Endoplasmic Reticulum Stress-Mediated Apoptosis Contributing to High Glucose Induced Vascular Smooth Muscle Cell Calcification. AB - Vascular calcification (VC) is a common feature in patients with type 2 diabetes mellitus, a metabolic disorder that is characterized by hyperglycemia (high blood glucose) in the context of insulin resistance and a relative lack of insulin. Recently, a few studies have indicated that a high concentration of glucose amplifies the osteogenesis of vascular smooth muscle cells (VSMCs). Some previous reports state that endoplasmic reticulum (ER) stress-mediated apoptosis was activated in and contributed to VC. However, whether or not high glucose could induce ER stress-mediated apoptosis and then involve the pathogenesis of VC remains unclear. The purpose of the present study was to investigate whether high blood glucose-induced VC in diabetes mellitus is caused by the ER response and subsequent apoptosis. We examined the effects of high glucose on the ER stress response of VSMCs. High glucose treatment drastically increased the ER stress response in VSMCs. The high glucose-induced osteoblastic differentiation of VSMCs was significantly attenuated by pretreatment with 500 MUM of 4-PBA (an ER stress inhibitor) prior to the exposure to high glucose, as evidenced by decreases in the expression of Runx2 and activity of alkaline phosphatase, as well as calcium nodules. These results suggest that high glucose induces the ER stress response and apoptosis, leading to high glucose-elicited VC. PMID- 26890315 TI - The role of social-cognitive and emotional factors on testicular self examination. AB - OBJECTIVE: This study determined the role of social-cognitive and affective factors in promoting testicular self-examination. METHODS: Male participants (N = 115) rated their perceptions of testicular cancer, social-cognitive variables (attitude, subjective norm, and perceived control), and their emotions towards testicular cancer (anxiety and shame) and testicular self-examination (anticipated regret and relief). Participants also stated whether or not they had performed a testicular self-examination within the last month. RESULTS: Perceived control and anticipated relief positively predicted testicular self-examination within the last month. Both these factors also positively predicted the intention to self-examine in the future. Intention was also positively predicted by attitude and negatively predicted by shame. CONCLUSIONS: These results highlight the importance of social-cognitive and emotional factors in promoting health screening. Targeting these factors might improve the effectiveness of testicular self-examination interventions. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890316 TI - Can Belief in a Just World Buffer Mood and Career Prospects of People in Need of Risk Protection? First Experimental Evidence. AB - Research indicates that individuals high in belief in a just world (BJW) are confident that they will not fall victim to unforeseeable disasters. The current study tested the hypothesis that BJW acts as buffer that serves to sustain mood and career prospects of those in need of risk protection. Threat was manipulated by confronting participants with risks regarding their career outlook, and individual differences in threat perception were measured by degree of uncertainty tolerance. As hypothesized, BJW helped protect the mood of participants threatened by serious career-related risks who were unable to tolerate uncertainty. The finding supported the buffer hypothesis regarding mood, but not career prospects, possibly due to a more conscious mindset or variability in self-efficacy. However, BJW was overall positively associated with career prospects. Moreover, it was suggested that BJW can also serve as a personal resource, not only protecting from risk, but also enhancing mood among those with high uncertainty tolerance. PMID- 26890317 TI - Comparison of use of diabetic medication and clinical guidelines in four Nordic countries. AB - BACKGROUND: Clinical guidelines form one of the cornerstones for providing high quality care for patients with diabetes. We compare the national guidelines and the use of glucose lowering medication for type 2 diabetes (T2D) in Denmark, Finland, Norway and Sweden. METHODS: We compared how guidelines take comprehensive care into consideration, what treatment targets and what antihyperglycemic medication was recommended. The use of glucose-lowering medication was based on the sales of diabetes drugs in these countries. RESULTS: All guidelines stress the importance of comprehensive diabetes care. Individualized glycemic targets are emphasized especially in the Danish and Finnish guidelines. In 2013, sulfonylureas were the most common second-line treatment after metformin in Denmark, Norway and Sweden; in Finland, this position was taken by DPP-4 inhibitors. Recommended initial insulin type for patients with T2D differs between the four countries. Danish, Norwegian and Swedish guidelines also take economic aspects into account. CONCLUSIONS: All guidelines stress regular and comprehensive diabetes care. Danish and Finnish guidelines strongly underline the importance of individualized glycemic targets. All guidelines recommend metformin as the initial oral antihyperglycemic drug. In relation to recommended second line drug therapy and initial insulin type for patients with T2D, the guidelines vary largely between the four countries. PMID- 26890318 TI - Can new passenger cars reduce pedestrian lower extremity injury? A review of geometrical changes of front-end design before and after regulatory efforts. AB - OBJECTIVE: Pedestrian lower extremity represents the most frequently injured body region in car-to-pedestrian accidents. The European Directive concerning pedestrian safety was established in 2003 for evaluating pedestrian protection performance of car models. However, design changes have not been quantified since then. The goal of this study was to investigate front-end profiles of representative passenger car models and the potential influence on pedestrian lower extremity injury risk. METHODS: The front-end styling of sedans and sport utility vehicles (SUV) released from 2008 to 2011 was characterized by the geometrical parameters related to pedestrian safety and compared to representative car models before 2003. The influence of geometrical design change on the resultant risk of injury to pedestrian lower extremity-that is, knee ligament rupture and long bone fracture-was estimated by a previously developed assessment tool assuming identical structural stiffness. Based on response surface generated from simulation results of a human body model (HBM), the tool provided kinematic and kinetic responses of pedestrian lower extremity resulted from a given car's front-end design. RESULTS: Newer passenger cars exhibited a "flatter" front-end design. The median value of the sedan models provided 87.5 mm less bottom depth, and the SUV models exhibited 94.7 mm less bottom depth. In the lateral impact configuration similar to that in the regulatory test methods, these geometrical changes tend to reduce the injury risk of human knee ligament rupture by 36.6 and 39.6% based on computational approximation. The geometrical changes did not significantly influence the long bone fracture risk. CONCLUSIONS: The present study reviewed the geometrical changes in car front-ends along with regulatory concerns regarding pedestrian safety. A preliminary quantitative benefit of the lower extremity injury reduction was estimated based on these geometrical features. Further investigation is recommended on the structural changes and inclusion of more accident scenarios. PMID- 26890319 TI - Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC. AB - We report on a case of intoxication with a mix of new psychoactive substances. A 38-year-old male was brought to the emergency department (ED) following the ingestion of an unknown drug in a suicide attempt. During the transport, he became progressively more somnolent and unresponsive to painful stimuli. Urine and stomach content were collected on admission to be screened for drugs of abuse and medicinal drugs. After admission, the patient's next of kin presented five small grip seal plastic bags containing different powders/crystals, and they were sent for analysis along with urine and stomach content to the toxicology laboratory. An easy and rapid sample preparation technique was applied for the extraction of urine and stomach content. Samples were extracted with liquid liquid extraction (LLE) technique and analysed using gas chromatography-mass spectrometry (GC-MS). A small amount of powder material from the bags was diluted in methanol and injected directly into the GC-MS instrument. Obtained spectra (EI) were evaluated against SWGDRUG library. Five different designer drugs were identified in the powder material, including synthetic cannabinoids (AB-CHMINACA, AB-FUBINACA) and synthetic cathinones (alpha-PHP, alpha-PVP and 4-CMC). With the exception of 4-CMC, all of these substances were also detected in the stomach content along with the prescription drugs. This is the first time that a positive identification of these five drugs has been made by a clinical laboratory in Slovenia. PMID- 26890320 TI - Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL. AB - OBJECTIVES: To investigate overall survival and prostate cancer-specific mortality in men with prostate cancer presenting with a PSA level <100 ng/mL at the time of diagnosis. PATIENTS: Five-thousand seven hundred and sixteen patients with prostate cancer and a recorded diagnostic PSA level extracted from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) database. Men included were diagnosed between January 1998 and August 2013. METHODS: Patients were divided into groups according to diagnostic PSA level: <20, 20 <=100, 100-<=200 ng/mL, 200-<=500 ng/mL, and >500 ng/mL. Outcomes measured include overall survival and prostate cancer-specific mortality. Clinical stage, Gleason score and the presence of bony metastasis was evaluated to determine if they were prognostic factors in patients with PSA over 100 at diagnosis. Cox proportional hazards and competing risks regression were used to model overall survival and prostate cancer-specific mortality outcomes respectively. RESULTS: Of this cohort, 241 patients (4.2%) had a diagnostic PSA level >100 ng/mL. Patients with PSA >100 ng/mL have a significant reduction in five (29.1% vs 62.5% vs 87%) and ten-year (18.2% vs 36.7% vs 70.7%) overall survival when compared to men with diagnostic PSA 20-100 and <20 ng/mL respectively. In this group, prostate cancer-specific mortality was associated with Gleason score and metastases, but not PSA level at diagnosis. Overall survival was associated with PSA level, Gleason score and age. There was a linear increase in risk (overall survival) as PSA increased until 200 and no association thereafter. Models of overall survival and prostate cancer-specific mortality incorporating a risk stratification developed by Izumi et al. predicted overall survival but not prostate cancer-specific mortality. The use of this stratification did not improve model accuracy. CONCLUSION: Only a small number of men (4.2%) with prostate cancer present with PSA >100 ng/mL at diagnosis. Overall survival at five and ten years was significantly poorer in patients with PSA >100 ng/mL. In this cohort of men presenting with PSA >100 at diagnosis, PSA level was not associated with prostate cancer-specific mortality. Gleason score and metastases are significant prognostic factors in this group of men. PMID- 26890321 TI - Sodium Chloride, NaCl/epsilon: New Force Field. AB - A new computational model for sodium chloride, the NaCl/epsilon, is proposed. The force field employed for the description of the NaCl is based on a set of radial particle-particle pair potentials involving Lennard-Jones (LJ) and Coulombic forces. The parametrization is obtained by fitting the density of the crystal and the density and the dielectric constant of the mixture of the salt with water at a diluted solution. Our model shows good agreement with the experimental values for the density and for the surface tension of the pure system, and for the density, the viscosity, the diffusion, and the dielectric constant for the mixture with water at various molal concentrations. The NaCl/epsilon together with the water TIP4P/epsilon models provide a good approximation for studying electrolyte solutions. PMID- 26890322 TI - Electrochemical Reduction of Carbon Dioxide to Methanol by Direct Injection of Electrons into Immobilized Enzymes on a Modified Electrode. AB - We present results for direct bio-electrocatalytic reduction of CO2 to C1 products using electrodes with immobilized enzymes. Enzymatic reduction reactions are well known from biological systems where CO2 is selectively reduced to formate, formaldehyde, or methanol at room temperature and ambient pressure. In the past, the use of such enzymatic reductions for CO2 was limited due to the necessity of a sacrificial co-enzyme, such as nicotinamide adenine dinucleotide (NADH), to supply electrons and the hydrogen equivalent. The method reported here in this paper operates without the co-enzyme NADH by directly injecting electrons from electrodes into immobilized enzymes. We demonstrate the immobilization of formate, formaldehyde, and alcohol dehydrogenases on one-and-the-same electrode for direct CO2 reduction. Carbon felt is used as working electrode material. An alginate-silicate hybrid gel matrix is used for the immobilization of the enzymes on the electrode. Generation of methanol is observed for the six-electron reduction with Faradaic efficiencies of around 10%. This method of immobilization of enzymes on electrodes offers the opportunity for electrochemical application of enzymatic electrodes to many reactions in which a substitution of the expensive sacrificial co-enzyme NADH is desired. PMID- 26890324 TI - Spinal Cord Stimulation and Augmentative Control Strategies for Leg Movement after Spinal Paralysis in Humans. AB - Severe spinal cord injury is a devastating condition, tearing apart long white matter tracts and causing paralysis and disability of body functions below the lesion. But caudal to most injuries, the majority of neurons forming the distributed propriospinal system, the localized gray matter spinal interneuronal circuitry, and spinal motoneuron populations are spared. Epidural spinal cord stimulation can gain access to this neural circuitry. This review focuses on the capability of the human lumbar spinal cord to generate stereotyped motor output underlying standing and stepping, as well as full weight-bearing standing and rhythmic muscle activation during assisted treadmill stepping in paralyzed individuals in response to spinal cord stimulation. By enhancing the excitability state of the spinal circuitry, the stimulation can have an enabling effect upon otherwise "silent" translesional volitional motor control. Strategies for achieving functional movement in patients with severe injuries based on minimal translesional intentional control, task-specific proprioceptive feedback, and next-generation spinal cord stimulation systems will be reviewed. The role of spinal cord stimulation can go well beyond the immediate generation of motor output. With recently developed training paradigms, it can become a major rehabilitation approach in spinal cord injury for augmenting and steering trans- and sublesional plasticity for lasting therapeutic benefits. PMID- 26890325 TI - A Semi-automated Approach to Preparing Antibody Cocktails for Immunophenotypic Analysis of Human Peripheral Blood. AB - Immunophenotyping of peripheral blood by flow cytometry determines changes in the frequency and activation status of peripheral leukocytes during disease and treatment. It has the potential to predict therapeutic efficacy and identify novel therapeutic targets. Whole blood staining utilizes unmanipulated blood, which minimizes artifacts that can occur during sample preparation. However, whole blood staining must also be done on freshly collected blood to ensure the integrity of the sample. Additionally, it is best to prepare antibody cocktails on the same day to avoid potential instability of tandem-dyes and prevent reagent interaction between brilliant violet dyes. Therefore, whole blood staining requires careful standardization to control for intra and inter-experimental variability. Here, we report deployment of an automated liquid handler equipped with a two-dimensional (2D) barcode reader into a standard process of making antibody cocktails for flow cytometry. Antibodies were transferred into 2D barcoded tubes arranged in a 96 well format and their contents compiled in a database. The liquid handler could then locate the source antibody vials by referencing antibody names within the database. Our method eliminated tedious coordination for positioning of source antibody tubes. It provided versatility allowing the user to easily change any number of details in the antibody dispensing process such as specific antibody to use, volume, and destination by modifying the database without rewriting the scripting in the software method for each assay. A proof of concept experiment achieved outstanding inter and intra- assay precision, demonstrated by replicate preparation of an 11-color, 17 antibody flow cytometry assay. These methodologies increased overall throughput for flow cytometry assays and facilitated daily preparation of the complex antibody cocktails required for the detailed phenotypic characterization of freshly collected anticoagulated peripheral blood. PMID- 26890326 TI - Outcomes and Predictors of Rebleeding After 2-Octyl Cyanoacrylate Injection in Acute Gastric Variceal Hemorrhage. AB - BACKGROUND AND AIM: Endoscopic injection of 2-octyl cyanoacrylate (2-OCA) is used on an off-label basis for gastric variceal hemorrhage (GVH) in the United States. We assessed the efficacy, safety, and predictors of rebleeding after gastric variceal obturation (GVO) with 2-OCA in patients with acute GVH. MATERIALS AND METHODS: A retrospective analysis was performed of patients with GVH who underwent 2-OCA injection for GVO over a 15-year period. Rates of acute hemostasis, predictors of rebleeding, and cyanoacrylate-related adverse events were assessed. RESULTS: A total of 95 patients (63 males, median age 59+/-14 y) were analyzed. Gastric varices were categorized as GOV-1 (3%), GOV-2 (61%), and isolated gastric varices type 1 (36%) per Sarin classification. Initial hemostasis was achieved in all patients. Successful GVO, defined as sustained hemostasis within a month after injection, was achieved in 87 (92%) patients. Failed GVO with in-hospital rebleeding was observed in 8 (8%) patients. On univariate analysis, only the model for end-stage liver disease score was associated with an increased risk of rebleeding (odds ratio 1.2; 95% confidence interval, 1.1-1.4; P<0.01). Glue-related adverse events consisted of pulmonary emboli in 2 patients (2.1%), resulting in death in 1 patient. All cause in hospital mortality was 13% due to uncontrolled gastric variceal rebleeding (n=3), renal failure (n=6), metastatic hepatocellular carcinoma (n=1), hemorrhagic stroke (n=1), and pulmonary embolism (n=1). CONCLUSIONS: Injection of 2-OCA was effective at achieving hemostasis in a high proportion of patients (92%) admitted for acute GVH. The risk of glue-related pulmonary embolism approximated 2% in our patient cohort, including 1 fatality. PMID- 26890327 TI - Cost Averted With Timely Fecal Microbiota Transplantation in the Management of Recurrent Clostridium difficile Infection in Alberta, Canada. AB - BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective in treating recurrent Clostridium difficile infection (RCDI). However, the ideal timing for offering FMT remains to be determined. Furthermore, the direct medical costs averted with timely FMT have not been examined. METHODS: A retrospective review of the Edmonton FMT program database included patients who received FMT for RCDI (October 2012 to September 2014). They were divided into 2 groups: those who received FMT after 2 recurrences (the timely FMT group) and those who received FMT after at least 3 recurrences (the delayed FMT group). The primary outcome was the difference in direct medical costs related to hospital admissions and emergency room visits due to CDI between the 2 groups. The secondary outcomes were RCDI cure rate and duration of RCDI in each group. RESULTS: A total of 75 patients were included: 30 received timely FMT, whereas 45 received delayed FMT. The mean difference in hospital length of stay and emergency room visits related to CDI were 13.8 days shorter and 1.3 visits fewer with timely FMT, associated with a mean cost saving of $29,842 per patient. Sensitivity analysis was performed to examine the effect of outliers and comorbities on the differential costs, and it was found that the differences in average cost per patient were more pronounced in those with Charlson comorbidity index >=3 compared with those with scores of 0 to 2. The cure rate was 94% (timely FMT group) and 93% (delayed FMT group). The mean duration of RCDI was 109 days (timely FMT group) and 281 days (delayed FMT group). CONCLUSIONS: Timely FMT can provide significant cost savings to health-care systems, especially for patients with multiple comorbidities. PMID- 26890328 TI - Comparison of Demographic and Clinical Characteristics of Hispanic and Asian Chronic Hepatitis B Patients in Southern California. AB - OBJECTIVES: There are few data regarding the clinical and serologic features of chronic hepatitis B (CHB) infection among Hispanics in the United States. The aims of this study were to compare and contrast clinical characteristics of Hispanic and Asian CHB patients. METHODS: Demographic, clinical, and laboratory data were collected from Hispanic and Asian CHB patients seen between January 2013 and May 2014 at Los Angeles County Hepatitis Clinic. RESULTS: A total of 55 Hispanic and 342 Asian CHB patients were identified. Almost all were foreign born. Compared with Asians, Hispanics were more likely to report heterosexual transmission (P<0.0001) and blood transfusion history (P<0.0001) as risk factors. Overall, 31% of Hispanics had HBV>2000 IU/mL compared with 54% of Asians (P=0.004).Significantly more Asian HBeAg-negative/anti-HBe-positive CHB patients had high HBV DNA levels (>2000 IU/mL) with elevated ALT compared with Hispanic patients (P=0.04). Compared with Asians, Hispanic CHB patients were more likely to have elevated ALT and low HBV DNA levels (P=0.001). Among CHB patients who received antiviral therapy, response was comparable among Hispanics and Asians. There were no Hispanic CHB patients who experienced spontaneous reactivation or developed hepatocellular carcinoma. CONCLUSIONS: There were important differences in the clinical, demographic, and serologic characteristics between Hispanic and Asian CHB. Response rate to antiviral therapy was comparable. Further studies of Hispanic CHB patients in the United States are warranted. PMID- 26890330 TI - Target-controlled Infusion Sedation for Colonoscopy Interventions. PMID- 26890329 TI - Trends in the Use of Endoscopic Retrograde Cholangiopancreatography for the Management of Chronic Pancreatitis in the United States. AB - GOALS: The aim of this study was to characterize current trends in the use of endoscopic retrograde cholangiopancreatography (ERCP) in the United States for patients hospitalized with chronic pancreatitis. BACKGROUND: Historically, ERCP was the primary tool for diagnostic and therapeutic management of chronic pancreatitis. With increased availability of magnetic resonance imaging and endoscopic ultrasound, indications for ERCP are being redefined. STUDY: We performed a retrospective cohort study using the Nationwide Inpatient Sample from 1998 to 2010. We identified patients with a primary discharge diagnosis of chronic pancreatitis who underwent ERCP. We excluded patients diagnosed with biliary, gallbladder, or pancreatic neoplasm and patients who underwent gallbladder or pancreatic operation during the same admission. We analyzed patient and hospital characteristics, length of stay, and in-hospital mortality, and adjusted for weighted sample schema. RESULTS: During the study period, 29,318 patients with chronic pancreatitis (mean age 52 y, 57.2% female) underwent ERCP during their hospitalization. The majority of patients were white (56.1%). The majority of procedures were performed at large (72.4%), urban (95.2%), and academic (69.0%) hospitals. Mean hospital charges were $32,929 (SE= $1605). Mean length of stay was 6 days (SE=0.3), with in-hospital mortality of 0.76%. Over the study period, the number of procedures has decreased significantly (P<0.001). CONCLUSIONS: In the United States, ERCP has been an important diagnostic and therapeutic tool for chronic pancreatitis. Over the last decade, ERCP has become an uncommon inpatient procedure for chronic pancreatitis. PMID- 26890331 TI - Abdominal Paracentesis Drainage Does Not Bring Extra Risk to Patients With Severe Acute Pancreatitis. PMID- 26890334 TI - Bimetallic Au2 Cu6 Nanoclusters: Strong Luminescence Induced by the Aggregation of Copper(I) Complexes with Gold(0) Species. AB - The concept of aggregation-induced emission (AIE) has been exploited to render non-luminescent Cu(I) SR complexes strongly luminescent. The Cu(I) SR complexes underwent controlled aggregation with Au(0) . Unlike previous AIE methods, our strategy does not require insoluble solutions or cations. X-ray crystallography validated the structure of this highly fluorescent nanocluster: Six thiolated Cu atoms are aggregated by two Au atoms (Au2 Cu6 nanoclusters). The quantum yield of this nanocluster is 11.7 %. DFT calculations imply that the fluorescence originates from ligand (aryl groups on the phosphine) to metal (Cu(I) ) charge transfer (LMCT). Furthermore, the aggregation is affected by the restriction of intramolecular rotation (RIR), and the high rigidity of the outer ligands enhances the fluorescence of the Au2 Cu6 nanoclusters. This study thus presents a novel strategy for enhancing the luminescence of metal nanoclusters (by the aggregation of active metal complexes with inert metal atoms), and also provides fundamental insights into the controllable synthesis of highly luminescent metal nanoclusters. PMID- 26890332 TI - DNA demethylation of the TIM-3 promoter is critical for its stable expression on T cells. AB - The T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is selectively expressed on terminally differentiated T helper 1 (Th1) cells and acts as a negative regulator that terminates Th1 responses. The dysregulation of TIM-3 expression on T cells is associated with several autoimmune phenotypes and with chronic viral infections; however, the mechanism of this regulation is unclear. In this study, we investigated the effect of DNA methylation on the expression of TIM-3. By analyzing the sequences of TIM-3 promoter regions in human and mouse, we identified a CpG island within the TIM-3 promoter and demonstrated that the promoter activity was controlled by DNA methylation. Furthermore, treatment with 5-aza-2'-deoxycytidine enhanced TIM-3 expression on mouse primary CD4(+) T cells under Th0-, Th1- or Th2-polarizing conditions. Finally, pyrosequencing analysis revealed that the methylation level of the TIM-3 promoter gradually decreased after each round of T-cell polarization, and this decrease was inversely correlated with TIM-3 expression. These data suggest that the DNA methylation of the TIM-3 promoter cooperates with lineage-specific transcription factors in the control of Th-cell development. In conclusion, DNA methylation-based regulation of TIM-3 may provide novel insights into understanding the dysregulation of TIM-3 expression under pathogenic conditions. PMID- 26890333 TI - The early onset of type 1 autoimmune hepatitis has a strong genetic influence: role of HLA and KIR genes. AB - We have previously reported a strong association between HLA-DRB1*1301 and type 1 pediatric autoimmune hepatitis (PAH) and between HLA-DR*0405 and adult autoimmune hepatitis (AAH). Because human killer cell immunoglobulin-like receptors are known to be associated with susceptibility to autoimmune diseases, we investigated the frequencies of HLA-A, B, C, DRB1 and KIR genes in 144 type 1 PAH and 86 AAH patients, which were compared with 273 healthy controls. We demonstrated in PAH the increased frequency of the functional form of KIR2DS4 Full Length (KIR2DS4-FL), which in combination with HLA-DRB1*1301 revealed a strong synergistic effect (odds ratio=36.5). PAH-KIR2DS4-FL+ subjects have shown an increased frequency of their putative HLA-C*02, 04 and 06 ligands. KIR analysis of PAH also revealed a decreased frequency of KIR2DL2 gene and its ligand. In contrast, AAH cases have shown a weaker increased frequency of KIR2DS4 FL, a lack of synergistic effect with HLA class II antigens and a moderate association with HLA-DRB1*0405. Of note, we demonstrated that liver T cells have a unique pattern of KIR expression. These results show a KIR gene involved in autoimmune hepatitis and suggest a stronger genetic influence for the early onset type I autoimmune hepatitis. PMID- 26890335 TI - Living with bipolar disorder: the impact on patients, spouses, and their marital relationship. AB - OBJECTIVES: Patients with bipolar disorder are characterized by an unusually high divorce rate. As such, the purpose of the present study was to uncover information relating specifically to the impact of bipolar disorder on patients and spouses individually, and on the marital relationship from the perspectives of both patients and spouses. METHODS: Eleven patients with bipolar disorder and ten spouses were interviewed separately about the impact of bipolar disorder on their lives and on their marital relationship. Data were analyzed using the grounded theory method. RESULTS: The impact of bipolar disorder for spouses included self-sacrifice, caregiving burden, emotional impact, and a sense of personal evolution. The impact of bipolar disorder on patients included an emotional impact, responsibility for self-care, and struggling socially and developmentally. When comparing patient and spouse perspectives on the impact of the disorder, neither the patient nor the spouse was able to accurately assess the impact of the disorder on their partner's lives. The impact of bipolar disorder on the relationship included volatility in the relationship, strengthening the relationship, weakening the relationship, and family planning. CONCLUSIONS: The research indicated that patients and partners alike struggle with the tremendous impact of bipolar disorder on their lives and on their relationships. Given the high rates of divorce and volatility in these relationships, healthcare professionals can provide (or refer to) emotional and practical support both to patients and spouses on their own, and as a couple in their clinics. PMID- 26890336 TI - Nano- and micro-based systems for immunotolerance induction in multiple sclerosis. AB - It is estimated that more than 2.5 million individuals worldwide have multiple sclerosis (MS). MS is an autoimmune neurodegenerative disease resulting from the destruction of the myelin sheath that enwraps axons driven by an immune cell attack to the central nervous system. Current therapeutic programs for MS focus in immunosuppression and more recently in the use of immunomodulatory molecules. These therapeutic approaches provide significant improvements in the management of the disease, but are frequently associated with an increased susceptibility of opportunistic infection. In this commentary, we highlight the application of nano and micro-technologies as emerging and innovative solutions for MS therapy with the potential to restore immune homeostasis via antigen-specific interactions. Furthermore, we propose and discuss the usage of a minimally invasive approach, namely microneedle patches, as a new therapeutic route. Microneedle patches for the delivery of specific antigens to restore immunotolerance in the context of multiple sclerosis. PMID- 26890337 TI - Buckwheat and Millet Affect Thermal, Rheological, and Gelling Properties of Wheat Flour. AB - Buckwheat (BF) and millet (MF) are recommended as healthy foods due to their unique chemical composition and health benefits. This study investigated the thermal and rheological properties of BF-WF (wheat flour) and MF-WF flour blends at various ratios (0:100 to 100:0). Increasing BF or MF concentration led to higher cold paste viscosity and setback viscosity of pasting properties gel adhesiveness, storage modulus (G') and loss modulus (G") of dynamic oscillatory rheology, and yield stress (sigma0 ) of flow curve of WF. BF and MF addition decreased peak viscosity and breakdown of pasting, gel hardness, swelling volume, and consistency coefficient (K) of flow curve of WF. Thermal properties of the blends appeared additive of that of individual flour. Nonadditive effects were observed for some property changes in the mixtures, and indicated interactions between flour components. This may provide a physicochemical basis for using BF and MF in formulating novel healthy products. PMID- 26890338 TI - Endoplasmic reticulum stress participates in inflammation-accelerated, lipid mediated injury of human glomerular mesangial cells. AB - AIM: The mechanism of lipid-mediated injury of human glomerular mesangial cells (HMCs) remains unclear. We investigated the association between endoplasmic reticulum (ER) stress and lipid-mediated injury in HMCs in vitro and the potential efficacy of a therapeutic approach targeting ER stress. METHODS: Human glomerular mesangial cells were exposed to low-density lipoprotein (LDL) and/or interleukin-1beta (IL-1beta). For evaluation of whether ER stress participates in lipid-mediated injury to HMCs, HMCs were pretreated with tunicamycin or treated with sodium 4-phenylbutyrate (4-PBA). RESULTS: Incubation of HMCs with LDL + IL 1beta significantly increased lipid accumulation and induced phenotypic changes. ER stress was induced in lipid-loaded HMCs, as indicated by upregulation of glucose-regulated protein 78 (GRP78) and protein kinase RNA-like ER kinase (PERK) proteins. Moreover, persistent ER stress increased expression of nuclear factor (NF)-kappaB p65 protein, fibronectin, and alpha-smooth muscle actin (alpha-SMA) mRNA partly through the PERK - eukaryotic initiation factor-2alpha (eIF2alpha) pathway. Preconditioning with ER stress by tunicamycin and inhibition of ER stress by 4-PBA both reversed the phenotypic changes and decreased lipid accumulation and inflammatory cytokine secretion by the PERK - eIF2alpha pathway. CONCLUSION: These data provide evidence that ER stress participates in inflammation associated with lipid-induced injury of HMCs. Modulation of ER stress may be a novel therapeutic approach for combating lipid-induced injury of HMCs. PMID- 26890339 TI - Polarized Neutron Diffraction to Probe Local Magnetic Anisotropy of a Low-Spin Fe(III) Complex. AB - We have determined by polarized neutron diffraction (PND) the low-temperature molecular magnetic susceptibility tensor of the anisotropic low-spin complex PPh4 [Fe(III) (Tp)(CN)3]?H2O. We found the existence of a pronounced molecular easy magnetization axis, almost parallel to the C3 pseudo-axis of the molecule, which also corresponds to a trigonal elongation direction of the octahedral coordination sphere of the Fe(III) ion. The PND results are coherent with electron paramagnetic resonance (EPR) spectroscopy, magnetometry, and ab initio investigations. Through this particular example, we demonstrate the capabilities of PND to provide a unique, direct, and straightforward picture of the magnetic anisotropy and susceptibility tensors, offering a clear-cut way to establish magneto-structural correlations in paramagnetic molecular complexes. PMID- 26890340 TI - Cluster of HIV Infections Attributed to Unsafe Injection Practices--Cambodia, December 1, 2014-February 28, 2015. AB - In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure. PMID- 26890341 TI - Stability of organic solar cells: challenges and strategies. AB - Organic solar cells (OSCs) present some advantages, such as simple preparation, light weight, low cost and large-area flexible fabrication, and have attracted much attention in recent years. Although the power conversion efficiencies have exceeded 10%, the inferior device stability still remains a great challenge. In this review, we summarize the factors limiting the stability of OSCs, such as metastable morphology, diffusion of electrodes and buffer layers, oxygen and water, irradiation, heating and mechanical stress, and survey recent progress in strategies to increase the stability of OSCs, such as material design, device engineering of active layers, employing inverted geometry, optimizing buffer layers, using stable electrodes and encapsulation. Some research areas of device stability that may deserve further attention are also discussed to help readers understand the challenges and opportunities in achieving high efficiency and high stability of OSCs towards future industrial manufacture. PMID- 26890342 TI - Isolated pregnancy-induced anti-thrombin deficiency in a woman with twin pregnancy. AB - A woman with twin pregnancy had a gradual decline in anti-thrombin (AT) activity from 72% at gestational week (GW) 29-3/7 , to 53% at GW31-2/7 , and to 41% at GW32-2/7 , at which time hypertension (148/90 mmHg) and proteinuria (protein-to creatinine ratio [P/Cr], 0.79 mg/mg) developed in the presence of normal platelet count (159 * 109 /L) and serum aspartate aminotransferase/lactate dehydrogenase (22/164 IU/L). AT product was given three times to maintain AT activity >50% and blood pressure was maintained below 155/95 mmHg with no treatment, but generalized edema with a weekly weight gain of 4.9 kg and increased proteinuria (to P/Cr, 7.6 mg/mg) required cesarean section at GW33-3/7 . This case highlights the occurrence of pregnancy-induced AT deficiency alone in the absence of any other abnormality, including hypertension, proteinuria, or thrombocytopenia. Measurement of AT activity was considered helpful for determination of the appropriate time for delivery in this patient. PMID- 26890343 TI - Bimodal Functionality in a Porous Covalent Triazine Framework by Rational Integration of an Electron-Rich and -Deficient Pore Surface. AB - A porous covalent triazine framework (CTF) consisting of both an electron deficient central triazine core and electron-rich aromatic building blocks is reported. Taking advantage of the dual nature of the pore surface, bimodal functionality has been achieved. The electron deficiency in the central core has been utilized to address one of the pertinent problems in chemical industries, namely separation of benzene from its cyclic saturated congener, that is, cyclohexane. Also, by virtue of the electron-rich aromatic rings with Lewis basic sites, aqueous-phase chemical sensing of a nitroaromatic compound of highly explosive nature (2,4,6-trinitrophenol; TNP) has been achieved. The present compound supersedes the performance of previously reported COFs in both the aspects. Notably, this reports the first example of pore-surface engineering leading to bimodal functionality in CTFs. PMID- 26890345 TI - Recurrent Neural Network for Computing Outer Inverse. AB - Two linear recurrent neural networks for generating outer inverses with prescribed range and null space are defined. Each of the proposed recurrent neural networks is based on the matrix-valued differential equation, a generalization of dynamic equations proposed earlier for the nonsingular matrix inversion, the Moore-Penrose inversion, as well as the Drazin inversion, under the condition of zero initial state. The application of the first approach is conditioned by the properties of the spectrum of a certain matrix; the second approach eliminates this drawback, though at the cost of increasing the number of matrix operations. The cases corresponding to the most common generalized inverses are defined. The conditions that ensure stability of the proposed neural network are presented. Illustrative examples present the results of numerical simulations. PMID- 26890344 TI - Causal Inference on Discrete Data via Estimating Distance Correlations. AB - In this article, we deal with the problem of inferring causal directions when the data are on discrete domain. By considering the distribution of the cause [Formula: see text] and the conditional distribution mapping cause to effect [Formula: see text] as independent random variables, we propose to infer the causal direction by comparing the distance correlation between [Formula: see text] and [Formula: see text] with the distance correlation between [Formula: see text] and [Formula: see text]. We infer that X causes Y if the dependence coefficient between [Formula: see text] and [Formula: see text] is smaller. Experiments are performed to show the performance of the proposed method. PMID- 26890346 TI - Feature-Based Attention by Lateral Spike Synchronization. AB - We introduce a neural model capable of feature selectiveness by spike-mediated synchronization through lateral synaptic couplings. For a stimulus containing two features, the attended one elicits a higher response. In the case of sequential single-feature stimuli, repetition of the attended feature also results in an enhanced response, exhibited by greater synchrony and higher spiking rates. PMID- 26890348 TI - A Mathematical Motivation for Complex-Valued Convolutional Networks. AB - A complex-valued convolutional network (convnet) implements the repeated application of the following composition of three operations, recursively applying the composition to an input vector of nonnegative real numbers: (1) convolution with complex-valued vectors, followed by (2) taking the absolute value of every entry of the resulting vectors, followed by (3) local averaging. For processing real-valued random vectors, complex-valued convnets can be viewed as data-driven multiscale windowed power spectra, data-driven multiscale windowed absolute spectra, data-driven multiwavelet absolute values, or (in their most general configuration) data-driven nonlinear multiwavelet packets. Indeed, complex-valued convnets can calculate multiscale windowed spectra when the convnet filters are windowed complex-valued exponentials. Standard real-valued convnets, using rectified linear units (ReLUs), sigmoidal (e.g., logistic or tanh) nonlinearities, or max pooling, for example, do not obviously exhibit the same exact correspondence with data-driven wavelets (whereas for complex-valued convnets, the correspondence is much more than just a vague analogy). Courtesy of the exact correspondence, the remarkably rich and rigorous body of mathematical analysis for wavelets applies directly to (complex-valued) convnets. PMID- 26890347 TI - Optimal Schedules in Multitask Motor Learning. AB - Although scheduling multiple tasks in motor learning to maximize long-term retention of performance is of great practical importance in sports training and motor rehabilitation after brain injury, it is unclear how to do so. We propose here a novel theoretical approach that uses optimal control theory and computational models of motor adaptation to determine schedules that maximize long-term retention predictively. Using Pontryagin's maximum principle, we derived a control law that determines the trial-by-trial task choice that maximizes overall delayed retention for all tasks, as predicted by the state space model. Simulations of a single session of adaptation with two tasks show that when task interference is high, there exists a threshold in relative task difficulty below which the alternating schedule is optimal. Only for large differences in task difficulties do optimal schedules assign more trials to the harder task. However, over the parameter range tested, alternating schedules yield long-term retention performance that is only slightly inferior to performance given by the true optimal schedules. Our results thus predict that in a large number of learning situations wherein tasks interfere, intermixing tasks with an equal number of trials is an effective strategy in enhancing long-term retention. PMID- 26890349 TI - Sampled-Data State Feedback Stabilization of Boolean Control Networks. AB - In this letter, we investigate the sampled-data state feedback control (SDSFC) problem of Boolean control networks (BCNs). Some necessary and sufficient conditions are obtained for the global stabilization of BCNs by SDSFC. Different from conventional state feedback controls, new phenomena observed the study of SDSFC. Based on the controllability matrix, we derive some necessary and sufficient conditions under which the trajectories of BCNs can be stabilized to a fixed point by piecewise constant control (PCC). It is proved that the global stabilization of BCNs under SDSFC is equivalent to that by PCC. Moreover, algorithms are given to construct the sampled-data state feedback controllers. Numerical examples are given to illustrate the efficiency of the obtained results. PMID- 26890351 TI - Vector Symbolic Spiking Neural Network Model of Hippocampal Subarea CA1 Novelty Detection Functionality. AB - A neural network model is presented of novelty detection in the CA1 subdomain of the hippocampal formation from the perspective of information flow. This computational model is restricted on several levels by both anatomical information about hippocampal circuitry and behavioral data from studies done in rats. Several studies report that the CA1 area broadcasts a generalized novelty signal in response to changes in the environment. Using the neural engineering framework developed by Eliasmith et al., a spiking neural network architecture is created that is able to compare high-dimensional vectors, symbolizing semantic information, according to the semantic pointer hypothesis. This model then computes the similarity between the vectors, as both direct inputs and a recalled memory from a long-term memory network by performing the dot-product operation in a novelty neural network architecture. The developed CA1 model agrees with available neuroanatomical data, as well as the presented behavioral data, and so it is a biologically realistic model of novelty detection in the hippocampus, which can provide a feasible explanation for experimentally observed dynamics. PMID- 26890350 TI - Downstream Effect of Ramping Neuronal Activity through Synapses with Short-Term Plasticity. AB - Ramping neuronal activity refers to spiking activity with a rate that increases quasi-linearly over time. It has been observed in multiple cortical areas and is correlated with evidence accumulation processes or timing. In this work, we investigated the downstream effect of ramping neuronal activity through synapses that display short-term facilitation (STF) or depression (STD). We obtained an analytical result for a synapse driven by deterministic linear ramping input that exhibits pure STF or STD and numerically investigated the general case when a synapse displays both STF and STD. We show that the analytical deterministic solution gives an accurate description of the averaging synaptic activation of many inputs converging onto a postsynaptic neuron, even when fluctuations in the ramping input are strong. Activation of a synapse with STF shows an initial cubical increase with time, followed by a linear ramping similar to a synapse without STF. Activation of a synapse with STD grows in time to a maximum before falling and reaching a plateau, and this steady state is independent of the slope of the ramping input. For a synapse displaying both STF and STD, an increase in the depression time constant from a value much smaller than the facilitation time constant tau(F) to a value much larger than tau(F) leads to a transition from facilitation dominance to depression dominance. Therefore, our work provides insights into the impact of ramping neuronal activity on downstream neurons through synapses that display short-term plasticity. In a perceptual decision making process, ramping activity has been observed in the parietal and prefrontal cortices, with a slope that decreases with task difficulty. Our work predicts that neurons downstream from such a decision circuit could instead display a firing plateau independent of the task difficulty, provided that the synaptic connection is endowed with short-term depression. PMID- 26890352 TI - Online Pairwise Learning Algorithms. AB - Pairwise learning usually refers to a learning task that involves a loss function depending on pairs of examples, among which the most notable ones are bipartite ranking, metric learning, and AUC maximization. In this letter we study an online algorithm for pairwise learning with a least-square loss function in an unconstrained setting of a reproducing kernel Hilbert space (RKHS) that we refer to as the Online Pairwise lEaRning Algorithm (OPERA). In contrast to existing works (Kar, Sriperumbudur, Jain, & Karnick, 2013 ; Wang, Khardon, Pechyony, & Jones, 2012 ), which require that the iterates are restricted to a bounded domain or the loss function is strongly convex, OPERA is associated with a non-strongly convex objective function and learns the target function in an unconstrained RKHS. Specifically, we establish a general theorem that guarantees the almost sure convergence for the last iterate of OPERA without any assumptions on the underlying distribution. Explicit convergence rates are derived under the condition of polynomially decaying step sizes. We also establish an interesting property for a family of widely used kernels in the setting of pairwise learning and illustrate the convergence results using such kernels. Our methodology mainly depends on the characterization of RKHSs using its associated integral operators and probability inequalities for random variables with values in a Hilbert space. PMID- 26890353 TI - Feature Selection for Ridge Regression with Provable Guarantees. AB - We introduce single-set spectral sparsification as a deterministic sampling-based feature selection technique for regularized least-squares classification, which is the classification analog to ridge regression. The method is unsupervised and gives worst-case guarantees of the generalization power of the classification function after feature selection with respect to the classification function obtained using all features. We also introduce leverage-score sampling as an unsupervised randomized feature selection method for ridge regression. We provide risk bounds for both single-set spectral sparsification and leverage-score sampling on ridge regression in the fixed design setting and show that the risk in the sampled space is comparable to the risk in the full-feature space. We perform experiments on synthetic and real-world data sets; a subset of TechTC-300 data sets, to support our theory. Experimental results indicate that the proposed methods perform better than the existing feature selection methods. PMID- 26890354 TI - Theoretical and Experimental Analyses of Tensor-Based Regression and Classification. AB - We theoretically and experimentally investigate tensor-based regression and classification. Our focus is regularization with various tensor norms, including the overlapped trace norm, the latent trace norm, and the scaled latent trace norm. We first give dual optimization methods using the alternating direction method of multipliers, which is computationally efficient when the number of training samples is moderate. We then theoretically derive an excess risk bound for each tensor norm and clarify their behavior. Finally, we perform extensive experiments using simulated and real data and demonstrate the superiority of tensor-based learning methods over vector- and matrix-based learning methods. PMID- 26890355 TI - Outcomes of artificial urinary sphincter placement in octogenarians. AB - OBJECTIVE: To evaluate the impact of patient age on device outcomes among patients undergoing primary artificial urinary sphincter. METHODS: A total of 1081 male patients who underwent primary artificial urinary sphincter placement from 1983 to 2011 were analyzed, including 91 men (8%) who were aged >80 years at the time of surgery. Revisions and explanations were compared between men stratified by decade of life. Hazard ratios adjusting for competing risks were used to determine the association with age and artificial urinary sphincter device outcomes (infection/erosion, urethral atrophy and malfunction), while overall device failure was estimated using Kaplan-Meier and Cox regression analysis. RESULTS: Patients aged >80 years were more likely to have coronary disease (P = 0.009), diabetes mellitus (P = 0.04), hypertension (P = 0.002) and lower body mass index (P < 0.0001). On multivariable analysis, patients aged >80 years were significantly more likely to experience device erosion or infection compared with a reference of patients aged <60 years (hazard ratio 4.13; P = 0.046), whereas there was no difference in those patients aged 60-70 years or 70 80 years compared with the reference group (P = 0.56 and 0.45). There was no significant difference in overall device survival between the age-stratified groups (P = 0.26). CONCLUSIONS: Although overall artificial urinary sphincter device survival is similar, patients aged >80 years are more likely to experience erosion or infection compared with younger patients. Despite this, the overall device failure rate is low, and artificial urinary sphincter might be considered for appropriately selected and counseled octogenarians. PMID- 26890357 TI - Forensic Occupational Therapy in Canada: The Current State of Practice. AB - Although occupational therapists have been practicing in forensic settings for many years, there is a paucity of literature regarding the nature of this practice in Canada. The purpose of this study was to describe the practices of Canadian occupational therapists in forensic mental health. An online survey was designed based on the Canadian Practice Process Framework. Following purposive and snowball sampling, responses were analysed with descriptive statistics and content analysis. Twenty-seven clinicians responded (56% response rate). Respondents indicated commonalities in workplaces, client caseloads and practice challenges. The outstanding need in Canada to demonstrate client outcomes through the use of evaluation instruments reflects those practice gaps identified internationally. Education, advocacy and research are critical areas for the development of Canadian forensic occupational therapy. Although findings heavily reflect one provincial context and may not be generalizable to nonhospital settings, a number of priority areas were identified. Future efforts should clarify the role of forensic occupational therapy to stakeholders, and validate their contributions through research that evaluates intervention efficacy and meaningful outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890356 TI - Repression of Wnt/beta-catenin response elements by p63 (TP63). AB - Submitted: TP63 (p63), a member of the tumor suppressor TP53 (p53) gene family, is expressed in keratinocyte stem cells and well-differentiated squamous cell carcinomas to maintain cellular potential for growth and differentiation. Controversially, activation of the Wnt/beta-catenin signaling by p63 (Patturajan M. et al., 2002, Cancer Cells) and inhibition of the target gene expression (Drewelus I. et al., 2010, Cell Cycle) have been reported. Upon p63 RNA-silencing in squamous cell carcinoma (SCC) lines, a few Wnt target gene expression substantially increased, while several target genes moderately decreased. Although DeltaNp63alpha, the most abundant isoform of p63, appeared to interact with protein phosphatase PP2A, neither GSK-3beta phosphorylation nor beta-catenin nuclear localization was altered by the loss of p63. As reported earlier, DeltaNp63alpha enhanced beta-catenin-dependent luc gene expression from pGL3-OT having 3 artificial Wnt response elements (WREs). However, this activation was detectable only in HEK293 cells examined so far, and involved a p53 family related sequence 5' to the WREs. In Wnt3-expressing SAOS-2 cells, DeltaNp63alpha rather strongly inhibited transcription of pGL3-OT. Importantly, DeltaNp63alpha repressed WREs isolated from the regulatory regions of MMP7. DeltaNp63alpha-TCF4 association occurred in their soluble forms in the nucleus. Furthermore, p63 and TCF4 coexisted at a WRE of MMP7 on the chromatin, where beta-catenin recruitment was attenuated. The combined results indicate that DeltaNp63alpha serves as a repressor that regulates beta-catenin-mediated gene expression. PMID- 26890359 TI - Strategies to increase the hygienic and economic value of fresh fish: Biopreservation using lactic acid bacteria of marine origin. AB - In this work we describe the development of a biopreservation strategy for fresh fish based on the use of bacteriocinogenic LAB of marine origin. For this purpose, two multibacteriocinogenic LAB strains, Lactobacillus curvatus BCS35 and Enterococcus faecium BNM58, previously isolated from fish and fish products were selected owing to their capability to inhibit the growth of several fish-spoilage and food-borne pathogenic bacteria. Two commercially important fish species were chosen, young hake (Merluccius merluccius) and megrim (Lepidorhombus boscii), and the specimens were acquired at the Marin (Pontevedra, Spain) retail fish market, after one night in the chilled hold of a near-shore fishing vessel. The biopreservation potential and the application strategies of these two LAB strains were first tested at a laboratory scale, where several batches of fresh fish were inoculated with: (i) the multibacteriocinogenic LAB culture(s) as protective culture(s); and/or (ii) their cell-free culture supernatant(s) as food ingredient(s), and (iii) the lyophilized bacteriocin preparation(s) as lyophilized food ingredient(s). All batches were stored in polystyrene boxes, permanently filled with ice at 0-2 degrees C, for 14 days. Microbiological analyses, as well as sensorial analyses, were carried out during the biopreservation trials. Subsequently, Lb. curvatus BCS35 was selected to up-scale the trials, and combinations of the three application methods were assayed. For this purpose, this strain was grown in a semi-industrial scale fermentor (150l) in modified MRS broth, and three batches of fresh fish were inoculated with the protective culture and/or food ingredient, and stored on ice in a chilled chamber at 0-2 degrees C at the Marin retail fish market for 14 days. Microbiological analyses were carried out during the storage period, showing that when Lb. curvatus BCS35 culture or the corresponding cell-free culture supernatant was used as protective culture or food ingredient, respectively, bacterial counts were significantly lower than those of the untreated control batches, both for young hake and megrim. In addition, the presence of Listeria spp. in megrim was inhibited in both analyses. The effect of protective culture or food ingredient on the sensory characteristics of fish was evaluated by an official fish appraiser from the Marin retail fish market, who concluded that all the biopreserved batches were worth a higher price in the fish market than the respective control batches, demonstrating that the multibacteriocinogenic strain of marine origin Lb. curvatus BCS35 may be considered as a suitable candidate for its application as fresh fish biopreservative. PMID- 26890358 TI - alpha-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration. AB - Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules, such as lipids, glycoproteins, and mucopolysaccharides. For instance, the lack of alpha-galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology. Enzyme replacement therapy, which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with Arginine-Glycine-Aspartic acid (RGD) peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS SUSP, based on the depressurization of a CO2 -expanded liquid organic solution, shows the great potential of this CO2 -based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest. PMID- 26890360 TI - A Capped Dipeptide Which Simultaneously Exhibits Gelation and Crystallization Behavior. AB - Short peptides capped at their N-terminus are often highly efficient gelators, yet notoriously difficult to crystallize. This is due to strong unidirectional interactions within fibers, resulting in structure propagation only along one direction. Here, we synthesize the N-capped dipeptide, benzimidazole diphenylalanine, which forms both hydrogels and single crystals. Even more remarkably, we show using atomic force microscopy the coexistence of these two distinct phases. We then use powder X-ray diffraction to investigate whether the single crystal structure can be extrapolated to the molecular arrangement within the hydrogel. The results suggest parallel beta-sheet arrangement as the dominant structural motif, challenging existing models for gelation of short peptides, and providing new directions for the future rational design of short peptide gelators. PMID- 26890361 TI - Whisking, Sniffing, and the Hippocampal theta-Rhythm: A Tale of Two Oscillators. AB - The hippocampus has unique access to neuronal activity across all of the neocortex. Yet an unanswered question is how the transfer of information between these structures is gated. One hypothesis involves temporal-locking of activity in the neocortex with that in the hippocampus. New data from the Matthew E. Diamond laboratory shows that the rhythmic neuronal activity that accompanies vibrissa-based sensation, in rats, transiently locks to ongoing hippocampal theta rhythmic activity during the sensory-gathering epoch of a discrimination task. This result complements past studies on the locking of sniffing and the theta rhythm as well as the relation of sniffing and whisking. An overarching possibility is that the preBotzinger inspiration oscillator, which paces whisking, can selectively lock with the theta-rhythm to traffic sensorimotor information between the rat's neocortex and hippocampus. PMID- 26890362 TI - Concerted Efforts to Control or Eliminate Neglected Tropical Diseases: How Much Health Will Be Gained? AB - BACKGROUND: The London Declaration (2012) was formulated to support and focus the control and elimination of ten neglected tropical diseases (NTDs), with targets for 2020 as formulated by the WHO Roadmap. Five NTDs (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths and trachoma) are to be controlled by preventive chemotherapy (PCT), and four (Chagas' disease, human African trypanosomiasis, leprosy and visceral leishmaniasis) by innovative and intensified disease management (IDM). Guinea worm, virtually eradicated, is not considered here. We aim to estimate the global health impact of meeting these targets in terms of averted morbidity, mortality, and disability adjusted life years (DALYs). METHODS: The Global Burden of Disease (GBD) 2010 study provides prevalence and burden estimates for all nine NTDs in 1990 and 2010, by country, age and sex, which were taken as the basis for our calculations. Estimates for other years were obtained by interpolating between 1990 (or the start-year of large-scale control efforts) and 2010, and further extrapolating until 2030, such that the 2020 targets were met. The NTD disease manifestations considered in the GBD study were analyzed as either reversible or irreversible. Health impacts were assessed by comparing the results of achieving the targets with the counterfactual, construed as the health burden had the 1990 (or 2010 if higher) situation continued unabated. PRINCIPLE FINDINGS/CONCLUSIONS: Our calculations show that meeting the targets will lead to about 600 million averted DALYs in the period 2011-2030, nearly equally distributed between PCT and IDM-NTDs, with the health gain amongst PCT-NTDs mostly (96%) due to averted disability and amongst IDM-NTDs largely (95%) from averted mortality. These health gains include about 150 million averted irreversible disease manifestations (e.g. blindness) and 5 million averted deaths. Control of soil-transmitted helminths accounts for one third of all averted DALYs. We conclude that the projected health impact of the London Declaration justifies the required efforts. PMID- 26890365 TI - Plagiarism: A Shared Responsibility of All, Current Situation, and Future Actions in Yemen. AB - As combating plagiarism is a shared responsibility of all, this article focuses on presenting the current situation of higher education in Yemen. The critical review of four implementable policy documents and interviews revealed the absence of research ethics code, research misconduct policy, and institutional policies in the country. This led to the presence of several acts of research dishonesty. The article concludes with an initiative for necessary future actions in the nation. PMID- 26890364 TI - Differential Evolutionary Selection and Natural Evolvability Observed in ALT Proteins of Human Filarial Parasites. AB - The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT 2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (omega) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by omega values was notably strongest on the region of ALT 2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by chi2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0.01) deviations from a normal distribution for both W. bancrofti and L. loa. The relationship between evolvability and selection in L. loa followed a second order polynomial distribution (R2 = 0.89), indicating that the two factors relate to one another in accordance with an additional unknown factor. Taken together, these findings indicate discrete evolutionary drivers acting on ALT-2 of the four organisms examined, and the described variation has implications for design of novel vaccines and diagnostic reagents. Additionally, this represents the first mathematical description of evolvability in a naturally occurring setting. PMID- 26890363 TI - Iron and cancer: recent insights. AB - Iron is an essential dietary element. However, the ability of iron to cycle between oxidized and reduced forms also renders it capable of contributing to free radical formation, which can have deleterious effects, including promutagenic effects that can potentiate tumor formation. Dysregulation of iron metabolism can increase cancer risk and promote tumor growth. Cancer cells exhibit an enhanced dependence on iron relative to their normal counterparts, a phenomenon we have termed iron addiction. Work conducted in the past few years has revealed new cellular processes and mechanisms that deepen our understanding of the link between iron and cancer. Control of iron efflux through the combined action of ferroportin, an iron efflux pump, and its regulator hepcidin appears to play an important role in tumorigenesis. Ferroptosis is a form of iron-dependent cell death involving the production of reactive oxygen species. Specific mechanisms involved in ferroptosis, including depletion of glutathione and inhibition of glutathione peroxidase 4, have been uncovered. Ferritinophagy is a newly identified mechanism for degradation of the iron storage protein ferritin. Perturbations of mechanisms that control transcripts encoding proteins that regulate iron have been observed in cancer cells, including differences in miRNA, methylation, and acetylation. These new insights may ultimately provide new therapeutic opportunities for treating cancer. PMID- 26890366 TI - Does Temporal Integration Occur for Unrecognizable Words in Visual Crowding? AB - Visual crowding-the inability to see an object when it is surrounded by flankers in the periphery-does not block semantic activation: unrecognizable words due to visual crowding still generated robust semantic priming in subsequent lexical decision tasks. Based on the previous finding, the current study further explored whether unrecognizable crowded words can be temporally integrated into a phrase. By showing one word at a time, we presented Chinese four-word idioms with either a congruent or incongruent ending word in order to examine whether the three preceding crowded words can be temporally integrated to form a semantic context so as to affect the processing of the ending word. Results from both behavioral (Experiment 1) and Event-Related Potential (Experiment 2 and 3) measures showed congruency effect in only the non-crowded condition, which does not support the existence of unconscious multi-word integration. Aside from four-word idioms, we also found that two-word (modifier + adjective combination) integration-the simplest kind of temporal semantic integration-did not occur in visual crowding (Experiment 4). Our findings suggest that integration of temporally separated words might require conscious awareness, at least under the timing conditions tested in the current study. PMID- 26890367 TI - Plant endosomal NHX antiporters: Activity and function. AB - The Arabidopsis NHX antiporter family contains eight members that are divided into three subclasses: vacuolar, endosomal, and plasma membrane. While the plasma membrane and vacuolar NHXs have been studied extensively, the activity and function of the endosomal NHXs are beginning to be discovered. AtNHX5 and AtNHX6 are endosomal Na(+),K(+)/H(+) antiporters that share high sequence similarity. They are localized in the Golgi, trans-Golgi network (TGN), and prevacuolear compartment (PVC). Studies have shown that AtNHX5 and AtNHX6 mediate K(+) and Na(+) transport, and regulate cellular pH homeostasis. Sequence alignment has found that AtNHX5 and AtNHX6 contain four conserved acidic amino acid residues in transmembrane domains that align with yeast and human NHXs. Three of these conserved acidic residues are critical for K(+) transport and seedling growth in Arabidopsis. Moreover, studies have shown that the precursors of the seed storage proteins are missorted to the apoplast in the nhx5 nhx6 knockout mutant, suggesting that AtNHX5 and AtNHX6 regulate protein transport into the vacuole. Further analysis found that AtNHX5 and AtNHX6 regulated the binding of VSR to its cargoes. Taken together, AtNHX5 and AtNHX6 play an important role in cellular ion and pH homeostasis, and are essential for protein transport into the vacuole. PMID- 26890368 TI - TNF-alpha and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals. AB - Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF alpha) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-alpha -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-alpha GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-alpha GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890369 TI - Novel real-time PCR assays for the specific detection of human infective Cryptosporidium species. PMID- 26890370 TI - Assessing agreement with multiple raters on correlated kappa statistics. AB - In clinical studies, it is often of interest to see the diagnostic agreement among clinicians on certain symptoms. Previous work has focused on the agreement between two clinicians under two different conditions or the agreement among multiple clinicians under one condition. Few have discussed the agreement study with a design where multiple clinicians examine the same group of patients under two different conditions. In this paper, we use the intraclass kappa statistic for assessing nominal scale agreement with such a design. We derive an explicit variance formula for the difference of correlated kappa statistics and conduct hypothesis testing for the equality of kappa statistics. Simulation studies show that the method performs well with realistic sample sizes and may be superior to a method that did not take into account the measurement dependence structure. The practical utility of the method is illustrated on data from an eosinophilic esophagitis (EoE) study. PMID- 26890371 TI - Liver Abscess Caused by Infection with Community-Acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. AB - We report a case of pyogenic liver abscess caused by community-acquired Klebsiella quasipneumoniae subsp. quasipneumoniae. The infecting isolate had 2 prominent features of hypervirulent K. pneumoniae strains: the capsular polysaccharide synthesis region for K1 serotype and the integrative and conjugative element ICEKp1, which encodes the virulence factors yersiniabactin, salmochelin, and RmpA. PMID- 26890375 TI - Microglia Response and In Vivo Therapeutic Potential of Methylprednisolone-Loaded Dendrimer Nanoparticles in Spinal Cord Injury. PMID- 26890372 TI - Validity and Responsiveness of the Trunk Impairment Scale and Trunk Control Measurement Scale in Young Individuals with Cerebral Palsy. AB - AIM: This study examines construct validity and responsiveness of the Trunk Impairment Scale (TIS) and Trunk Control Measurement Scale (TCMS) in individuals with cerebral palsy (CP). METHODS: Twenty-six individuals with CP (nine males), 8 29 years (mean age 17.6) with gross motor function corresponding to GMFCS I-IV, participated in three weeks of intensive and varied physical training at a health sports center. Trunk control was assessed with the TIS (includes three subscales) and TCMS (includes three subscales), and gross motor function with the Gross Motor Function Measure 66 item set (GMFM-66-IS), before and after the training period. The GMFM-66-IS was used as a comparison measure. RESULTS: The median score of the TCMS subscale dynamic sitting balance, reaching (DSB-R), increased from 6 to 7 (range: 1-10; p = .031), and there was a median change of 3 points in GMFM-66-IS score (p = .036). There were no significant changes in the TIS. The correlations (Spearman's rho), between the TIS, TCMS, and the GMFM-66-IS (pre scores), ranged between 0.57 and 0.75 (p< .003). Correlations between change scores (pre- and post-scores) were low, and not statistically significant. However, the TCMS DSB-R change score correlated significantly with hours spent on "trunk-targeted training" like paddling/rowing (rho = 0.66; p = .003) and horseback riding (rho = 0.54; p = .011). CONCLUSIONS: Our results support construct validity of the TIS and TCMS in young individuals with CP, whereas responsiveness could not be documented. However, the correlations between the TCMS DSB-R change score and hours spent on ''trunk-targeted training'' suggest that this subscale may have the potential to be used in intervention studies. PMID- 26890379 TI - Suicidality among immigrants: Application of the interpersonal-psychological theory. AB - Immigrants constitute a significant percentage of the total population living in the United States; however, there is a paucity of research unique to suicidality among immigrants. The present article examines the applicability of the three variables of the interpersonal-psychological theory of suicidal behavior-acquired capability for suicide, sense of thwarted belongingness, and perceived burdensomeness-to conceptualize, assess, and treat suicidality among immigrants. Risk and protective factors and mechanisms are discussed in the context of 2 case studies and immigrant paradox. Clinical implications include assessment and treatment of immigrant-specific experiences. Obstacles to treatment and future research directions are presented. PMID- 26890381 TI - Joint model for left-censored longitudinal data, recurrent events and terminal event: Predictive abilities of tumor burden for cancer evolution with application to the FFCD 2000-05 trial. AB - In oncology, the international WHO and RECIST criteria have allowed the standardization of tumor response evaluation in order to identify the time of disease progression. These semi-quantitative measurements are often used as endpoints in phase II and phase III trials to study the efficacy of new therapies. However, through categorization of the continuous tumor size, information can be lost and they can be challenged by recently developed methods of modeling biomarkers in a longitudinal way. Thus, it is of interest to compare the predictive ability of cancer progressions based on categorical criteria and quantitative measures of tumor size (left-censored due to detection limit problems) and/or appearance of new lesions on overall survival. We propose a joint model for a simultaneous analysis of three types of data: a longitudinal marker, recurrent events, and a terminal event. The model allows to determine in a randomized clinical trial on which particular component treatment acts mostly. A simulation study is performed and shows that the proposed trivariate model is appropriate for practical use. We propose statistical tools that evaluate predictive accuracy for joint models to compare our model to models based on categorical criteria and their components. We apply the model to a randomized phase III clinical trial of metastatic colorectal cancer, conducted by the Federation Francophone de Cancerologie Digestive (FFCD 2000-05 trial), which assigned 410 patients to two therapeutic strategies with multiple successive chemotherapy regimens. PMID- 26890380 TI - Evidence for Inbreeding and Genetic Differentiation among Geographic Populations of the Saprophytic Mushroom Trogia venenata from Southwestern China. AB - During the past 40 years, more than 400 Sudden Unexplained Deaths (SUDs) have occurred in Yunnan, southwestern China. Epidemiological and toxicological analyses suggested that a newly discovered mushroom called Trogia venenata was the leading culprit for SUDs. At present, relatively little is known about the genetics and natural history of this mushroom. In this study, we analyzed the sequence variation at four DNA fragments among 232 fruiting bodies of T. venenata collected from seven locations. Our ITS sequence analyses confirmed that all the isolates belonged to the same species. The widespread presence of sequence heterozygosity within many strains at each of three protein-coding genes suggested that the fruiting bodies were diploid, dikaryotic or heterokaryotic. Within individual geographic populations, we found significant deviations of genotype frequencies from Hardy-Weinberg expectations, with the overall observed heterozygosity lower than that expected under random mating, consistent with prevalent inbreeding within local populations. The geographic populations were overall genetically differentiated. Interestingly, while a positive correlation was found between population genetic distance and geographic distance, there was little correlation between genetic distance and barium concentration difference for the geographic populations. Our results suggest frequent inbreeding, geographic structuring, and limited gene flow among geographic populations of T. venenata from southwestern China. PMID- 26890382 TI - Perioperative management of penile transplantation. PMID- 26890383 TI - Polyelectrolytes to produce nanosized polydopamine. AB - "Polydopamine" (PDA) is the oxidation product of dopamine and can be obtained as thin films covering the surface of all kinds of known materials and simultaneously as insoluble and useless precipitates from dopamine solutions in the presence of appropriate oxidants. The valorization of such precipitates to obtain stable suspensions of functional nanomaterials is highly desirable owing to the chemical and optical properties of PDA. We show that a vast repertoire of polyelectrolytes polycations as well as polyanions, allow to control the size of PDA particles in the 10-100 nm size range. Simultaneously to the production of smaller nanoparticles, a progressive inhibition of PDA deposition on the surface of quartz plates (as well as on the surface of the reaction vessel) is found as the concentration of the polyelectrolytes is increased in the dopamine solution. The mechanism of size control-inhibition of film deposition is investigated in the particular case of poly(allylamine) but remains not understood in the case of polyanions. PMID- 26890384 TI - Green synthesis of Pd nanoparticles mediated by Euphorbia thymifolia L. leaf extract: Catalytic activity for cyanation of aryl iodides under ligand-free conditions. AB - Pd nanoparticles (NPs) were synthesized by using aqueous extract of leaves of Euphorbia thymifolia L., a non-toxic ecofriendly material. The catalytic activity of the Pd NPs was investigated in the cyanation of aryl iodides using K4Fe(CN)6 as the cyanating agent under ligand-free conditions. The nitriles were obtained in good to excellent yield and the catalyst can be recovered and reused for five times without significant loss of catalytic activity. PMID- 26890385 TI - Foam stabilisation using surfactant exfoliated graphene. AB - Liquid-air foams have been stabilised using a suspension of graphene particles at very low particle loadings. The suspension was prepared through the liquid phase exfoliation of graphite in the presence of the non-ionic tri-block surfactant, Pluronic(r) F108. The graphene particles possess an extremely high aspect ratio, with lateral dimensions of between 0.1 and 1.3 MUm as evidenced by TEM imaging. The particles were shown to exhibit a number of other properties known to favour stabilisation of foam structures. Particle surface activity was confirmed through surface tension measurements, suggesting the particles favour adsorption at the air-water interface. The evolution of bubble size distributions over time indicated the presence of particles yielded improvements to foam stability due to a reduction in disproportionation. Foam stability measurements showed a non linear relationship between foam half-life and graphene concentration, indicative of the rate at which particles adsorb at bubble surfaces. The wettability of the graphene particles was altered upon addition of alkali metal chlorides, with the stability of the foams being enhanced according to the series Na(+)>Li(+)>K(+)>Cs(+). This effect is indicative of the relative hydration capacity of each salt with respect to the surfactant, which is adsorbed along the graphene plane as a result of the exfoliation process. Thus, surfactant exfoliated graphene particles exhibit a number of different features that demonstrate efficient application of high-aspect ratio particles in the customisation and enhancement of foams. PMID- 26890386 TI - Influence of pore size distribution on the adsorption of phenol on PET-based activated carbons. AB - The role of pore size distribution in the adsorption of phenol in aqueous solutions on polyethylene terephthalate (PET)-based activated carbons (ACs) has been analyzed. The ACs were prepared from PET and mixtures of PET with coal-tar pitch (CTP) by means of carbonization and subsequent steam and carbon dioxide activation at 850 and 950 degrees C, respectively. The resultant ACs were characterized on the basis of similarities in their surface chemical features and differences in their micropore size distributions. The adsorption of phenol was carried out in static conditions at ambient temperature. The pseudo-second order kinetic model and Langmuir model were found to fit the experimental data very well. The different adsorption capacities of the ACs towards phenol were attributed to differences in their micropore size distributions. Adsorption capacity was favoured by the volume of pores with a size smaller than 1.4 nm; but restricted by pores smaller than 0.8 nm. PMID- 26890387 TI - Controlling particle size in the Stober process and incorporation of calcium. AB - The Stober process is commonly used for synthesising spherical silica particles. This article reports the first comprehensive study of how the process variables can be used to obtain monodispersed particles of specific size. The modal particle size could be selected within in the range 20-500 nm. There is great therapeutic potential for bioactive glass nanoparticles, as they can be internalised within cells and perform sustained delivery of active ions. Biodegradable bioactive glass nanoparticles are also used in nanocomposites. Modification of the Stober process so that the particles can contain cations such as calcium, whilst maintaining monodispersity, is desirable. Here, whilst calcium incorporation is achieved, with a homogenous distribution, careful characterisation shows that much of the calcium is not incorporated. A maximum of 10 mol% CaO can be achieved and previous reports are likely to have overestimated the amount of calcium incorporated. PMID- 26890388 TI - "The Effects of Cognitive Behavioral Therapy as an Anti-Depressive Treatment is Falling: A Meta-Analysis": Correction to Johnsen and Friborg (2015). AB - Reports an error in "The effects of cognitive behavioral therapy as an anti depressive treatment is falling: A meta-analysis" by Tom J. Johnsen and Oddgeir Friborg (Psychological Bulletin, 2015[Jul], Vol 141[4], 747-768). There are several numerical errors in the flowchart summarizing the selection and exclusion of studies as contained in Figure 1. The correct number of titles not further investigated should be 27,381; abstracts rejected should be 1,181; Excluded, different treatment form should be (94). The errors do not affect the results or conclusions of the study as the final number of meta-analysable studies are the same as originally reported. (The following abstract of the original article appeared in record 2015-20361-001.) A meta-analysis examining temporal changes (time trends) in the effects of cognitive behavioral therapy (CBT) as a treatment for unipolar depression was conducted. A comprehensive search of psychotherapy trials yielded 70 eligible studies from 1977 to 2014. Effect sizes (ES) were quantified as Hedge's g based on the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HRSD). Rates of remission were also registered. The publication year of each study was examined as a linear metaregression predictor of ES, and as part of a 2-way interaction with other moderators (Year * Moderator). The average ES of the BDI was 1.58 (95% CI [1.43, 1.74]), and 1.69 for the HRSD (95% CI [1.48, 1.89]). Subgroup analyses revealed that women profited more from therapy than did men (p < .05). Experienced psychologists (g = 1.55) achieved better results (p < .01) than less experienced student therapists (g = 0.98). The metaregressions examining the temporal trends indicated that the effects of CBT have declined linearly and steadily since its introduction, as measured by patients' self-reports (the BDI, p < .001), clinicians' ratings (the HRSD, p < .01) and rates of remission (p < .01). Subgroup analyses confirmed that the declining trend was present in both within group (pre/post) designs (p < .01) and controlled trial designs (p = .02). Thus, modern CBT clinical trials seemingly provided less relief from depressive symptoms as compared with the seminal trials. Potential causes and possible implications for future studies are discussed. PMID- 26890389 TI - Cerebrovascular disease in children with HIV-1 infection. AB - An estimated 3.2 million children worldwide have human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) has resulted in prolonged survival, leading to an increase in complications previously recognized in adults. Children with HIV infection have increased risk of cerebrovascular disease from multiple aetiologies including HIV-associated vasculopathy, opportunistic vasculitis, cardioembolism or coagulopathy, all of which may be secondary to the infection. Prevalence of cerebrovascular disease in HIV-infected children is underestimated because of limited neuroimaging in low and middle income countries, silent events without overt motor manifestations, and mislabeling as HIV encephalopathy for non motor manifestations such as behavioural and cognitive difficulties. No management guidelines for cerebrovascular disease in HIV-infected children exist but common practices target risk factors for stroke in low and middle income countries. Where capacity permits, screening for opportunistic infections, vasculitis, coagulopathy and cardioembolism is important. Optimising virological suppression, correction of anaemia, control of seizures and aspirin prophylaxis are management priorities. Neurosurgical interventions may have a role. PMID- 26890390 TI - The use of the impedance measurements to distinguish between fresh and frozen thawed chicken breast muscle. AB - An impedance system was built to differentiate fresh chicken breasts from those that had been frozen and thawed. Inserting needle electrode pairs of the detecting probe aligned with the longitudinal direction of muscle myofibers (PL) gave more satisfactory results. Learning vector quantization neural network (LVQNN) and partial least square-discriminant analysis (PLS-DA) were employed to acquire the prediction accuracy. The results demonstrated that the model using LVQNN achieved a satisfactory prediction accuracy, with a discrimination accuracy for fresh breasts of 100%. Additionally, the recognition results for a single frozen-thawed cycle were greater than 90%, and for two cycles were greater than 88%. The values obtained from PLS-DA were somewhat lower than for LVQNN, being 100% for fresh samples, in excess of 90% for single frozen-thawed cycle and more than 84% for those that had been multiple frozen-thawed. In conclusion, these results showed that the impedance system is a simple and effective application for the discrimination of fresh chicken breasts from frozen-thawed ones. PMID- 26890391 TI - Effect of different aging temperatures prior to freezing on meat quality attributes of frozen/thawed lamb loins. AB - The objective of this study was to determine the effect of different aging temperatures prior to freezing on quality attributes of frozen/thawed lamb loins. The loins (M. longissimus lumborum; n=32) were randomly allocated to one of the four different aging/freezing treatments: aged only (-1.5 degrees C for 14 days) and aged (-1.5 degrees C for 14 days, 3 degrees C for 8 days, or 7 degrees C for 8days) then frozen/thawed loins. The loins aged at elevated temperatures (3 degrees C or 7 degrees C) for 8 days had equivalent shear force, protein degradation and purge loss values compared to the loins aged at -1.5 degrees C for 14 days (P>0.05). However, significantly higher drip loss and less color stability were observed in the loins with increasing aging temperatures compared to the loins aged at -1.5 degrees C. These results suggest that application of elevated aging temperatures could shorten required aging periods prior to freezing, while not adversely affecting tenderness and purge loss of frozen/thawed meat. PMID- 26890392 TI - Mitochondrial abundance and efficiency contribute to lean color of dark cutting beef. AB - Beef carcasses exhibiting four levels of dark cutting severity (DCS): Severe, Moderate, Mild, and Shady were compared to Control carcasses to investigate biochemical traits contributing to the dark cutting condition. Color attributes of Longissimus lumborum (LL) were measured after grading and during simulated retail display. Mitochondrial abundance and efficiency, bloomed oxymyoglobin, reducing ability, glycolytic potential, myoglobin concentration, and protein solubility and oxidation were determined. Glycolytic potential and lactate concentrations decreased (P<0.05) as DCS increased. Residual glycogen was greater (P<0.05) in steaks from Control carcasses compared to DCS classes. Generally, as DCS increased, LL steaks were darker and less red in color (P<0.05). Increased (P<0.05) oxygen consumption and reducing ability coincided with greater myoglobin concentration and greater abundance of less efficient mitochondria as DCS increased (P<0.05). These data suggest the dark cutting condition is associated with greater oxidative metabolism coupled with less efficient mitochondria resulting in depletion of glycogen during stress. PMID- 26890393 TI - The effect of skatole and androstenone on consumer response towards fresh pork from m. longissimus thoracis et lumborum and m. semimembranosus. AB - Consumer liking was assessed for boneless chops (m. longissimus thoracis et lumborum) and schnitzels (m. semimembranosus) from castrates and entire male pigs with an androstenone content of up to 9.4 ppm and a skatole content of up to 0.92 ppm in the back fat. Skatole affected both odour and flavour as assessed by trained sensory panellists (P<0.05-P<0.001), while androstenone particularly affected flavour (P<0.01-P<0.001). Furthermore, the skatole compound seemed to be more important in explaining the presence of boar taint in the chops, while androstenone seemed to be more important for the schnitzels. For the chops, tenderness was the most important attribute for consumer liking independently of both the androstenone and skatole contents (P<0.001). Furthermore, increasing contents of both androstenone (P=0.05) and skatole (P=0.04) resulted in a decreased liking of the chops. Skatole was the most important factor regarding consumer response towards the schnitzels (P=0.03). The very low liking scores for both chops and schnitzels were mainly attributable to the androstenone content. PMID- 26890394 TI - Synthesis, Photophysical, and Biological Evaluation of Sulfated Polyglycerol Dendronized Perylenebisimides (PBIs)--A Promising Platform for Anti-Inflammatory Theranostic Agents? AB - A set of four water-soluble perylene bisimides (PBI) based on sulfated polyglycerol (PGS) dendrons were developed, their photophysical properties determined via UV/vis and fluorescence spectroscopy, and their performance as possible anti-inflammatory agents evaluated via biological in vitro studies. It could be shown that in contrast to charge neutral PG-PBIs the introduction of the additional electrostatic repulsion forces leads to a decrease in the dendron generation necessary for aggregation suppression, allowing the preparation of PBIs with fluorescence quantum yields of >95% with a considerable decreased synthetic effort. Furthermore, the values determined for L-selectin binding down to the nanomolar range, their limited impact on blood coagulation, and their minor activation of the complement system renders these systems ideal for anti inflammatory purposes. PMID- 26890395 TI - Quantitative analysis of iontophoretic drug delivery from micropipettes. AB - Microiontophoresis is a drug delivery method in which an electric current is used to eject molecular species from a micropipette. It has been primarily utilized for neurochemical investigations, but is limited due to difficulty controlling and determining the ejected quantity. Consequently the concentration of an ejected species and the extent of the affected region are relegated to various methods of approximation. To address this, we investigated the principles underlying ejection rates and examined the concentration distribution in microiontophoresis using a combination of electrochemical, chromatographic, and fluorescence-based approaches. This involved a principal focus on how the iontophoretic barrel solution affects ejection characteristics. The ion ejection rate displayed a direct correspondence to the ionic mole fraction, regardless of the ejection current polarity. In contrast, neutral molecules are ejected by electroosmotic flow (EOF) at a rate proportional to the barrel solution concentration. Furthermore, the presence of EOF was observed from barrels containing high ionic strength solutions. In practice, use of a retaining current draws extracellular ions into the barrel and will alter the barrel solution composition. Even in the absence of a retaining current, diffusional exchange at the barrel tip will occur. Thus behavior of successive ejections may slightly differ. To account for this, electrochemical or fluorescence markers can be incorporated into the barrel solution in order to compare ejection quantities. These may also be used to provide an estimate of the ejected amount and distribution provided accurate use of calibration procedures. PMID- 26890397 TI - Genomics Politics through Space and Time: The Case of Bioinformatics in Brazil. AB - The emergence of scientific disciplines, as well as the policies aimed to steer them, have geographical implications. This becomes visible in areas such as genomics and related fields. In this paper, the relation between scientific evolution, political decisions and geographical configuration is studied. The recent formation of bioinformatics in Brazil is focused on. The study involves an analysis of data collected on the website of CNPq, a funding agency attached to the Ministry of Science and Technology. Furthermore, I conducted fieldwork in four cities, interviewing 15 bioinformaticians. In the history of Brazilian bioinformatics, three periods can be identified. In the first period (1900-1996), bioinformatics was actually absent, but biology research groups were formed which would subsequently explore bioinformatics. The second period (1997-2006) was marked by the emergence of the discipline and geographical concentration of major research groups in the southern part of Brazil. A third period can be pointed to (2007-2014), in which political choices have turned geographical diffusion and institutional equality into a national target. As a consequence of the recent shifts, genomics and bioinformatics researchers have been involved in a debate, some defending the existence of few specialized research and sequencing platforms, whereas others welcoming the constitution of a scientific scenario based on decentralized platforms. I defend an intermediate solution, whereby some places would be selected to be genomics hubs. This would fit the regional diversity of this vast country, in addition to tackling the scientific weaknesses of the northern area. PMID- 26890398 TI - A meta-review of school-based disaster interventions for child and adolescent survivors. AB - BACKGROUND: Children and adolescents are among the most vulnerable groups affected by natural and man-made disaster. To better understand research and practice concerning mental health and psychosocial support efforts in humanitarian settings, the authors conducted a comprehensive review of all intervention programmes within the past decade that universally targeted children and adolescents who were exposed to a natural and/or man-made disaster. METHODS: We searched PubMed, PsychINFO, Cochrane Library and CINAHL for mental health and psychosocial interventions (MHPSS) involving children and adolescents. A total of 11 studies, 4 from natural disasters and 7 from conflict-affected areas met the inclusion criteria. Effect sizes were calculated using a random effects model for studies in post-natural disaster and war/terrorist-affected settings separately. RESULTS: The weighted mean effect sizes for interventions in both settings were statistically significant: -0.308, 95% CI=-0.54- -0.07, z=-2.58, p=0.010 after a natural disaster, and -0.514, 95% CI=-0.80 to -0.23, z=-3.57, p<0.001 in conflict areas. This indicates that MHPSS interventions in both disaster settings resulted in a reduction in PTSD symptoms compared to the control. CONCLUSIONS: This review suggests that school-based, universal programmes that are conducted by teachers or local paraprofessionals are effective in reducing PTSD symptoms in children and adolescents. The few studies meeting the inclusion criteria of this study demonstrate the need for further expansion of statistical methods and study designs to test for the effects of interventions in challenging humanitarian settings. PMID- 26890396 TI - Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas. AB - Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs. PMID- 26890400 TI - A validational study of the Ironson-Woods Spirituality/Religiousness Index in Nigerian adolescents. AB - BACKGROUND: The mental health impact of spirituality/religiousness is widely recognised and studied in Western countries, but less so in developing nations, partly because of lack of valid instruments for such studies. OBJECTIVES: The objective of the study was to determine the convergent validity of the Ironson Woods Spirituality/Religiousness Index (IWSRI) in school attending Nigerian adolescents, and any relationship between spirituality/religiousness and mental health status. METHODS: The 25-item IWSRI, the "Age Universal" Religious Orientation Scale (ROS) and the 28-item General Health Questionnaire (GHQ) were administered to 300 randomly selected final year senior secondary students, aged 16 to 19 years, in Benin City. Responses were analysed using SPSS version 16 to determine the internal consistency for reliability, and correlation scores for convergent validity, of the IWSRI. RESULTS: Cronbach's alpha for the total IWSRI scale was 0.91; and for each of the two spirituality and two religiousness subscales of the IWSRI, these were quite high as well. The correlation of IWSRI with ROS intrinsic (r=0.47, p=0.00) and extrinsic personal religiosity (r=0.22, p=0.00) were significant. There was a significant difference in the IWSRI mean scores of GHQ cases and non-cases (t=4.30, p=0.00). CONCLUSION: IWSRI has acceptable psychometric properties, and therefore applicable in measuring spirituality and religiousness in Nigerian adolescents. PMID- 26890399 TI - "Wine you get every day, but a child you can't replace": The perceived impact of parental drinking on child outcomes in a South African township. AB - OBJECTIVE: This study explored the perceived impact of parental drinking on children in a South African township where alcohol abuse is prevalent and high levels of existing poverty and violence may exacerbate potential consequences on children. METHOD: Qualitative in-depth interviews were conducted with 92 male and female participants recruited from alcohol-serving venues in Cape Town, South Africa. RESULTS: Grounded theory analyses revealed three major aspects of parental drinking - intoxication, venue attendance and expenditures on alcohol - which participants linked to negative proximal outcomes (e.g., child neglect, abuse and exposure to alcohol culture) and long-term outcomes (e.g., fractured parent-child relationships and problematic youth behaviours). In addition, preliminary accounts from some participants suggested that parents may experience tensions between desires to reduce drinking for child-related reasons and complex factors maintaining their drinking behaviour, including the use of alcohol to cope with stressors and trauma. CONCLUSIONS: This study provides novel insights into the consequences and motivations of parental drinking in a high-risk context. Contextual risks (e.g., poverty and violence) that exacerbate the impact of parental drinking on children may be the same factors that continue to shape intergenerational alcohol use in this community. Findings highlight opportunities for further research and interventions to support child protection in South Africa. PMID- 26890401 TI - An expressive art group intervention for sexually abused adolescent females. AB - OBJECTIVE: South Africa has a high prevalence of sexual abuse of children and adolescents. Among the numerous adverse consequences of sexual abuse is the difficulty survivors may experience in developing positive self-esteem and maintaining positive relationships. In a low resource setting, an expressive art group intervention tailored to female adolescents who have been sexually abused was implemented and its value explored. METHOD: Six adolescents met for 10 weekly sessions which included expressive art activities, followed by reflective group discussions. The value of the intervention was explored using a qualitative research design with limited quantitative data. RESULTS: The participants reported that the group intervention relieved their sense of isolation and contributed to their ability to express emotions and develop self-awareness. Participants reported more positive self-esteem and improved interpersonal closeness. The intervention helped participants to find new meaning in painful experiences which contributed to personal growth. CONCLUSIONS: The group dynamics, expressive art activities and reflective group discussions contributed to the therapeutic value of the intervention. The expressive art group intervention showed value as an alternative therapeutic strategy in a low resource setting for female adolescents who have experienced sexual abuse. An experimental design could follow to confirm the effectiveness of the intervention. PMID- 26890402 TI - Prodromal psychotic symptoms and psychological distress among secondary school students in Abeokuta, Nigeria. AB - OBJECTIVE: This study aimed to investigate the relationship between prodromal psychotic symptoms and psychological distress among Nigerian adolescents. METHOD: Students (n=508) were randomly selected from secondary schools in Abeokuta, Nigeria. A socio-demographic questionnaire, the Prodromal Questionnaire-Brief Version (PQ-B) and the Strengths and Difficulties Questionnaire (SDQ) were administered to each student. RESULTS: The mean age of the students was 15.4 years (SD 1.3), with most (63%) being female. More than half (55.3%) reported having had a lifetime experience of major life event (20.9% in the preceding 6 months) while 13.9% had experienced bullying or abuse (5.1% in the preceding 6 months). The prevalence of prodromal symptoms was 20.9% (95% CI 0.174-0.244). Abnormal scores in emotional and conduct problems were seen in 11.8% and 6% respectively, while 7.3% had abnormal scores in each of the hyperactivity and peer problems subscales of the SDQ. Abnormality in prosocial behaviour was found in 1.8% of students, with overall abnormality in 4.9%. Regression analysis showed that prodromal symptoms were predicted by female sex, lifetime and 6 month history of major life event, and lifetime and 6 month history of bullying or abuse. Prodromal symptoms were also predicted by higher total SDQ scores and higher scores in all domains of psychological distress except the prosocial domain. CONCLUSION: The study showed a relationship between reported prodromal symptoms and the occurrence of psychological distress. It also showed that early childhood trauma may be a predisposing factor to the early stages of development of psychosis, with female children being especially prone in the years of adolescence. PMID- 26890404 TI - Anion Sensors as Logic Gates: A Close Encounter? AB - Computers have become smarter, smaller, and more efficient due to the downscaling of silicon-based components. Top-down miniaturisation of silicon-based computer components is fast reaching its limitations because of physical constraints and economical non-feasibility. Therefore, the possibility of a bottom-up approach that uses molecules to build nano-sized devices has been initiated. As a result, molecular logic gates based on chemical inputs and measurable optical outputs have captured significant attention very recently. In addition, it would be interesting if such molecular logic gates could be developed by making use of ion sensors, which can give significantly sensitive output information. This review provides a brief introduction to anion receptors, molecular logic gates, a comprehensive review on describing recent advances and progress on development of ion receptors for molecular logic gates, and a brief idea about the application of molecular logic gates. PMID- 26890405 TI - Different preferences between United States and European vitreoretinal surgeons: personal observations. AB - PURPOSE OF REVIEW: This article describes the author's personal observations on different preferences in surgical technique and surgical setting between vitreoretinal specialists in the USA and Europe. These impressions, although clearly subjective, derive from the author's extensive experience with, and connection to, many vitreoretinal centers and surgeons around the world in a wide variety of venues. RECENT FINDINGS: Although the results of surgery and the availability of information and instrumentation are quite comparable on both sides, vitreoretinal surgeons in the USA are more likely to use local anesthesia, an outpatient setting, perform phakic vitrectomy, use gas as opposed to oil as a tamponade, use pneumatic retinopexy for certain cases, place an anterior chamber lens for secondary implantation, and perform intravitreal injections in the office or exam room. In addition, European colleagues more commonly perform combined phacoemulsification with intraocular lens implantation at the time of vitrectomy, use perfluorochemicals during retinal detachment surgery, and utilize heavy silicone oils. SUMMARY: These observations suggest that many factors, both medical and nonmedical, influence vitreoretinal surgeons and result in differing preferences for surgical techniques and surgical setting. PMID- 26890406 TI - Highly Pathogenic Avian Influenza A(H5N8) Viruses Reintroduced into South Korea by Migratory Waterfowl, 2014-2015. AB - Highly pathogenic avian influenza A(H5N8) viruses were isolated from migratory waterfowl in South Korea during fall 2014-winter 2015, a recurrence after initial introduction in winter 2014. These reappeared viruses were phylogenetically distinct from isolates circulating in poultry farms in South Korea. PMID- 26890407 TI - Waterpipe Tobacco Smoking and Susceptibility to Cigarette Smoking Among Young Adults in the United States, 2012-2013. AB - INTRODUCTION: Waterpipe tobacco smoking, also known as hookah and shisha, has surged in popularity among young people in the United States. Waterpipe is also increasingly becoming the first tobacco product that young people try. Given the limited access to and limited portability of waterpipes, waterpipe smokers who become more nicotine dependent over time may be more likely to turn to cigarettes. This study examined the relationship between waterpipe tobacco smoking and susceptibility to cigarette smoking among young adults in the United States. METHODS: Using data from the 2012-2013 National Adult Tobacco Survey, a nationally representative sample of US adults, we reported rates of current waterpipe smoking and susceptibility to cigarette smoking by demographic characteristics and by use of other tobacco products among survey participants aged 18 to 24 years. Multivariable logistic regression was used to examine the relationship between current waterpipe smoking and susceptibility to cigarette smoking, defined as the lack of a firm intention not to smoke soon or within the next year. RESULTS: Of 2,528 young adults who had never established cigarette smoking, 15.7% (n = 398) reported being waterpipe smokers (every day or some days [n = 97; 3.8%] or rarely [n = 301; 11.9%]); 44.2% (176/398) of waterpipe smokers reported being susceptible to cigarette smoking. Those who smoked waterpipe rarely were 2.3 times as susceptible to cigarette smoking as those who were not current waterpipe smokers (OR = 2.3; 95% CI, 1.6-3.4). CONCLUSION: Current waterpipe smoking is associated with susceptibility to cigarette smoking among young adults in the United States. Longitudinal studies are needed to demonstrate causality between waterpipe smoking and initiation of cigarette smoking. PMID- 26890408 TI - How to Conduct Store Observations of Tobacco Marketing and Products. AB - As tobacco companies continue to heavily market their products at the point of sale, tobacco control groups seek strategies to combat the negative effects of this marketing. Store observations, which have been widely used by researchers and practitioners alike, are an excellent surveillance tool. This article provides a guide for public health practitioners interested in working in the tobacco retail environment by detailing the steps involved in conducting store observations of tobacco marketing and products including 1) obtaining tobacco product retailer lists, 2) creating measures, 3) selecting a mode of data collection, 4) training data collectors, and 5) analyzing data. We also highlight issues that may arise while in the field and provide information on disseminating results of store observations, including the potential policy implications. PMID- 26890409 TI - Legal Regulation of Sodium Consumption to Reduce Chronic Conditions. AB - In the United States, tens of thousands of Americans die each year of heart disease, stroke, or other chronic conditions tied to hypertension from long-term overconsumption of sodium compounds. Major strides to lower dietary sodium have been made over decades, but the goal of reducing Americans' daily consumption is elusive. The Food and Drug Administration (FDA) has been urged to consider stronger regulatory limits on sodium, especially in processed and prepared foods. Still, FDA categorizes salt (and many other sodium compounds) as "generally recognized as safe," meaning they can be added to foods when ingested in reasonable amounts. Legal reforms or actions at each level of government offer traditional and new routes to improving chronic disease outcomes. However, using law as a public health tool must be assessed carefully, given potential trade offs and unproven efficacy. PMID- 26890410 TI - Cryopreservation of Endothelial Cells in Various Cryoprotective Agents and Media Vitrification versus Slow Freezing Methods. AB - Vitrification of endothelial cells (MHECT-5) has not previously been compared with controlled slow freezing methods under standardized conditions. To identify the best cryopreservation technique, we evaluated vitrification and standardized controlled-rate -1 degrees C/minute cell freezing in a -80 degrees C freezer and tested four cryoprotective agents (CPA), namely dimethyl sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), and glycerol (GLY), and two media, namely Dulbecco's modified Eagle medium Ham's F-12 (DMEM)and K+-modified TiProtec (K+TiP), which is a high-potassium-containing medium. Numbers of viable cells in proliferation were evaluated by the CellTiter 96(r) AQueous One Solution Cell Proliferation Assay (Promega Corporation, Mannheim, Germany). To detect the exact frozen cell number per cryo vial, DNA content was measured by using Hoechst 33258 dye prior to analysis. Thus, results could be evaluated unconstrained by absolute cell number. Thawed cells were cultured in 25 cm2 cell culture flasks to confluence and examined daily by phase contrast imaging. With regard to cell recovery immediately after thawing, DMSO was the most suitable CPA combined with K+TiP in vitrification (99 +/-0.5%) and with DMEM in slow freezing (92 +/-1.6%). The most viable cells in proliferation after three days of culture were obtained in cells vitrificated by using GLY with K+TiP (308 +/-34%) and PG with DMEM in slow freezing (280 +/-27%). PMID- 26890411 TI - Small Players Ruling the Hard Game: siRNA in Bone Regeneration. AB - Silencing gene expression through a sequence-specific manner can be achieved by small interfering RNAs (siRNAs). The discovery of this process has opened the doors to the development of siRNA therapeutics. Although several preclinical and clinical studies have shown great promise in the treatment of neurological disorders, cancers, dominant disorders, and viral infections with siRNA, siRNA therapy is still gaining ground in musculoskeletal tissue repair and bone regeneration. Here we present a comprehensive review of the literature to summarize different siRNA delivery strategies utilized to enhance bone regeneration. With advancement in understanding the targetable biological pathways involved in bone regeneration and also the rapid progress in siRNA technologies, application of siRNA for bone regeneration has great therapeutic potential. High rates of musculoskeletal injuries and diseases, and their inevitable consequences, impose a huge financial burden on individuals and healthcare systems worldwide. PMID- 26890412 TI - Driver's obesity and road crash risks in the United States. AB - OBJECTIVE: We assessed obesity trends in U.S. drivers involved in fatal crashes since 1999 and distinguished whether crash risk factors were different between obese and nonobese drivers. METHODS: We included only drivers of passenger cars involved in fatal traffic crashes between January 1, 1999, and December 31, 2012. Obesity was classified according to the World Health Organization guidelines and profiled between 1999 and 2012 using the adjusted prevalence ratio (aPR) from log binomial regression models. Differences in crash risks (e.g., driver's fatality, drunk driving, seat belt nonuse) between obese and nonobese drivers were estimated as adjusted odds ratios (aORs) using logistic regression models. RESULTS: A total of 753,024 U.S. drivers were involved in fatal crashes, for which obesity information was available for 534,887. About 56% (n = 299,078) were driving passenger cars. The prevalence of class I obesity increased from 10% in 1999 to 14% in 2012 (aPR = 1.50, 95% confidence interval [CI], 1.42-1.58), class II obesity from 3 to 5% (aPR = 2.22, 95% CI, 2.05-3.01), and class III obesity from 1 to 2% (aPR = 2.65; 95% CI, 2.27-3.10). Compared to nonobese controls, obese drivers had significantly higher risks for fatality (1.10 <= aOR <= 1.47), seat belt nonuse (1.00 <= aOR <= 1.21), need for extrication (1.01 <= aOR <= 1.23), and ambulance transport time >=30 min (1.01 <= aOR <= 1.28). Compared to nonobese controls, obese drivers were less likely to drink drive (0.41 <= aOR <= 0.72) or speed >65 mph (0.78 <= aOR <= 0.93). CONCLUSION: The rising national prevalence of obesity extends to U.S. drivers involved in fatal crashes and indicates the need to improve seat belt use, vehicle design, and postcrash care for this vulnerable population. PMID- 26890413 TI - Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy. AB - Autophagy has recently emerged as an important cellular process for the maintenance of skeletal muscle health and function. Excessive autophagy can trigger muscle catabolism, leading to atrophy. In contrast, reduced autophagic flux is a characteristic of several muscle diseases, including Duchenne muscular dystrophy, the most common and severe inherited muscle disorder. Recent evidence demonstrates that enhanced reactive oxygen species (ROS) production by CYBB/NOX2 impairs autophagy in muscles from the dmd/mdx mouse, a genetic model of Duchenne muscular dystrophy. Statins decrease CYBB/NOX2 expression and activity and stimulate autophagy in skeletal muscle. Therefore, we treated dmd/mdx mice with simvastatin and showed decreased CYBB/NOX2-mediated oxidative stress and enhanced autophagy induction. This was accompanied by reduced muscle damage, inflammation and fibrosis, and increased muscle force production. Our data suggest that increased autophagy may be a potential mechanism by which simvastatin improves skeletal muscle health and function in muscular dystrophy. PMID- 26890414 TI - Mask-less deposition of Au-SnO2 nanocomposites on CMOS MEMS platform for ethanol detection. AB - Here we report on the mask-less deposition of Au-SnO2 nanocomposites with a silicon-on-insulator (SOI) complementary metal oxide semiconductor (CMOS) micro electro mechanical system (MEMS) platform through the use of dip pen nanolithography (DPN) to create a low-cost ethanol sensor. MEMS technology is used in order to achieve low power consumption, by the employment of a membrane structure formed using deep reactive ion etching technique. The device consists of an embedded tungsten micro-heater with gold interdigitated electrodes on top of the SOI membrane. The tungsten micro-heater is used to raise the membrane temperature up to its operating temperature and the electrodes are used to measure the resistance of the nanocomposite sensing layer. The CMOS MEMS devices have high electro-thermal efficiency, with 8.2 degrees C temperature increase per mW power of consumption. The sensing material (Au-SnO2 nanocomposite) was synthesised starting from SnO nanoplates, then Au nanoparticles were attached chemically to the surface of SnO nanoplates, finally the mixture was heated at 700 degrees C in an oven in air for 4 h. This composite material was sonicated for 2 h in terpineol to make a viscous homogeneous slurry and then 'written' directly across the electrode area using the DPN technique without any mask. The devices were characterised by exposure to ethanol vapour in humid air in the concentration range of 100-1000 ppm. The sensitivity varied from 1.2 to 0.27 ppm( 1) for 100-1000 ppm of ethanol at 10% relative humid air. Selectivity measurements showed that the sensors were selective towards ethanol when they were exposed to acetone and toluene. PMID- 26890415 TI - Revealing the signature of dipolar interactions in dynamic spectra of polydisperse magnetic nanoparticles. AB - We investigate, via a modified mean field approach, the dynamic magnetic response of a polydisperse dipolar suspension to a weak, linearly polarised, AC field. We introduce an additional term into the Fokker-Planck equation, which takes into account dipole-dipole interaction in the form of the first order perturbation, and allows for particle polydispersity. The analytical expressions, obtained for the real and imaginary dynamic susceptibilities, predict three measurable effects: the increase of the real part low-frequency plateaux; the enhanced growth of the imaginary part in the low-frequency range; and the shift of the imaginary part maximum. Our theoretical predictions find an experimental confirmation and explain the changes in the spectrum. PMID- 26890417 TI - Large-quantity and continuous preparation of two-dimensional nanosheets. AB - With the increasing demand for two-dimensional (2D) nanosheets, such as graphene, hexagonal boron nitride (h-BN), and MoS2 and WS2 nanosheets, finding a simple and feasible method to obtain nanosheets is crucial. Here, we present a high efficiency exfoliation method to obtain abundant and superior graphene, h-BN, MoS2, and WS2 nanosheets in aqueous solution. The obtained 2D nanosheets are very thin, especially MoS2 and WS2 nanosheets which are below 1 nm. PMID- 26890418 TI - Linking adult hippocampal neurogenesis with human physiology and disease. AB - We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890419 TI - PKCalpha Deficiency in Mice Is Associated with Pulmonary Vascular Hyperresponsiveness to Thromboxane A2 and Increased Thromboxane Receptor Expression. AB - Pulmonary vascular hyperresponsiveness is a main characteristic of pulmonary arterial hypertension (PAH). In PAH patients, elevated levels of the vasoconstrictors thromboxane A2 (TXA2), endothelin (ET)-1 and serotonin further contribute to pulmonary hypertension. Protein kinase C (PKC) isozyme alpha (PKCalpha) is a known modulator of smooth muscle cell contraction. However, the effects of PKCalpha deficiency on pulmonary vasoconstriction have not yet been investigated. Thus, the role of PKCalpha in pulmonary vascular responsiveness to the TXA2 analog U46619, ET-1, serotonin and acute hypoxia was investigated in isolated lungs of PKCalpha-/- mice and corresponding wild-type mice, with or without prior administration of the PKC inhibitor bisindolylmaleimide I or Go6976. mRNA was quantified from microdissected intrapulmonary arteries. We found that broad-spectrum PKC inhibition reduced pulmonary vascular responsiveness to ET-1 and acute hypoxia and, by trend, to U46619. Analogously, selective inhibition of conventional PKC isozymes or PKCalpha deficiency reduced ET-1 evoked pulmonary vasoconstriction. The pulmonary vasopressor response to serotonin was unaffected by either broad PKC inhibition or PKCalpha deficiency. Surprisingly, PKCalpha-/- mice showed pulmonary vascular hyperresponsiveness to U46619 and increased TXA2 receptor (TP receptor) expression in the intrapulmonary arteries. To conclude, PKCalpha regulates ET-1-induced pulmonary vasoconstriction. However, PKCalpha deficiency leads to pulmonary vascular hyperresponsiveness to TXA2, possibly via increased pulmonary arterial TP receptor expression. PMID- 26890416 TI - Quality Evaluation of Potentilla fruticosa L. by High Performance Liquid Chromatography Fingerprinting Associated with Chemometric Methods. AB - The present study was performed to assess the quality of Potentilla fruticosa L. sampled from distinct regions of China using high performance liquid chromatography (HPLC) fingerprinting coupled with a suite of chemometric methods. For this quantitative analysis, the main active phytochemical compositions and the antioxidant activity in P. fruticosa were also investigated. Considering the high percentages and antioxidant activities of phytochemicals, P. fruticosa samples from Kangding, Sichuan were selected as the most valuable raw materials. Similarity analysis (SA) of HPLC fingerprints, hierarchical cluster analysis (HCA), principle component analysis (PCA), and discriminant analysis (DA) were further employed to provide accurate classification and quality estimates of P. fruticosa. Two principal components (PCs) were collected by PCA. PC1 separated samples from Kangding, Sichuan, capturing 57.64% of the variance, whereas PC2 contributed to further separation, capturing 18.97% of the variance. Two kinds of discriminant functions with a 100% discrimination ratio were constructed. The results strongly supported the conclusion that the eight samples from different regions were clustered into three major groups, corresponding with their morphological classification, for which HPLC analysis confirmed the considerable variation in phytochemical compositions and that P. fruticosa samples from Kangding, Sichuan were of high quality. The results of SA, HCA, PCA, and DA were in agreement and performed well for the quality assessment of P. fruticosa. Consequently, HPLC fingerprinting coupled with chemometric techniques provides a highly flexible and reliable method for the quality evaluation of traditional Chinese medicines. PMID- 26890420 TI - Subjective visual and haptic vertical in young and elderly. AB - Perception of verticality can be assessed in two different ways: measuring of subjective visual vertical (SVV) and subjective haptic vertical (SHV). The evidence on aging of SVV and SVH is not conclusive and there is just little knowledge focused on this issue. The aim of this study was to compare accuracy of perception of SVV and SHV between groups of young and elderly healthy subjects. SVV examination was performed using the bucket test. An experimental tactile device was used to assess perceived SHV. Measurements of SVV and SHV were made in 27 young healthy and 30 elderly healthy subjects, both groups were right-handed due to self-report. SHV estimated position was significantly different (p< 0.01) in young and elderly (counterclockwise shift of 0.72 +/- 3.70 degrees and 3.51 +/- 3.99 degrees , respectively) and the SHV range (4.17 +/- 5.40 degrees and 9.64 +/- 7.42 degrees , respectively) was also different (p< 0.01). The differences were caused by significant difference in the supination maneuver (clockwise rod rotation, p< 0.001) which resulted in counterclockwise shift of 2.80 +/- 4.90 degrees and 8.33 +/- 4.62 degrees in young and elderly respectively. Pronation part of the SHV task (counterclockwise rod rotation) did not significantly differ between groups. SVV estimated position and range were not statistically different between young and elderly. These results provide evidence that the ability to detect SVV is not impaired, SHV seems also not to be affected by aging but there may be methodologic issues in SHV testing in elderly which should be controlled for in future studies. Results of both pronation and supination maneuvers should be provided along with SHV position. PMID- 26890421 TI - Visual perception of upright: Head tilt, visual errors and viewing eye. AB - BACKGROUND: Perception of upright is often assessed by aligning a luminous line to the subjective visual vertical (SVV). OBJECTIVE: Here we investigated the effects of visual line rotation and viewing eye on SVV responses and whether there was any change with head tilt. METHODS: SVV was measured using a forced choice paradigm and by combining the following conditions in 22 healthy subjects: head position (20 degrees left tilt, upright and 20 degrees right tilt), viewing eye (left eye, both eyes and right eye) and direction of visual line rotation (clockwise [CW] and counter clockwise [CCW]). RESULTS: The accuracy and precision of SVV responses were not different between the viewing eye conditions in all head positions (P> 0.05, Kruskal-Wallis test). The accuracy of SVV responses was % significantly different between the CW and CCW line rotations (p ~ 0.0001; Kruskal-Wallis test) and SVV was tilted in the same direction as the line rotation. This effect of line rotation was however not consistent across head tilts and was only present in the upright and right tilt head positions. The accuracy of SVV responses showed a higher variability among subjects in the left head tilt position with no significant difference between the CW and CCW line rotations (P> 0.05; post-hoc Dunn's test). CONCLUSIONS: In spite of the challenges to the estimate of upright with head tilt, normal subjects did remarkably well irrespective of the viewing eye. The physiological significance of the asymmetry in the effect of line rotation between the head tilt positions is unclear but it %may suggest suggests a lateralizing effect of head tilt on the visual perception of upright. PMID- 26890422 TI - Variants in the KCNE1 or KCNE3 gene and risk of Meniere's disease: A meta analysis. AB - BACKGROUND: Meniere's disease (MD) is defined as an idiopathic disorder of the inner ear characterized by the triad of tinnitus, vertigo, and sensorineural hearing loss. Although many studies have evaluated the association between variants in the KCNE1 or KCNE3 gene and MD risk, debates still exist. OBJECTIVE: Our aim is to evaluate the association between KCNE gene variants, including KCNE1 rs1805127 and KCNE3 rs2270676, and the risk of MD by a systematic review. METHODS: We searched the literature in PubMed, SCOPUS and EMBASE through May 2015. We calculated pooled odds ratios (OR) and 95% confidence intervals (CIs) using a fixed-effects model or a random-effects model for the risk to MD associated with different KCNE gene variants. The heterogeneity assumption decided the effect model. RESULTS: A total of three relevant studies, with 302 MD cases and 515 controls, were included in this meta-analysis. The results indicated that neither the KCNE1 rs1805127 variant (for G vs. A: OR = 0.724, 95%CI 0.320, 1.638, P= 0.438), nor the KCNE3 rs2270676 variant (for T vs. C: OR = 0.714, 95%CI 0.327, 1.559, P = 0.398) was associated with MD risk. CONCLUSIONS: Based on current evidence from published studies, neither of the two variants from KCNE was significantly associated with the risk of MD. Larger studies with mixed ethnicity subjects and stratified by clinical and sub-clinical characteristics are needed to validate our findings. PMID- 26890423 TI - Recovery times of stance and gait balance control after an acute unilateral peripheral vestibular deficit. AB - BACKGROUND: Acute unilateral peripheral vestibular deficit (aUPVD) patients have balance deficits that can improve after several weeks. Determining differences in vestibulo-spinal reflex (VSR) influences on balance control and vestibular ocular reflex (VOR) responses with peripheral recovery and central compensation would provide insights into CNS plasticity mechanisms. Also, clinically, knowing when balance control is approximately normal again should contribute to decisions about working ability after aUPVD. Usually VORs are employed for this purpose, despite a lack of knowledge about correlations with balance control. Given this background, we examined whether balance and VOR measures improve similarly and are correlated. Further whether balance improvements are different for stance and gait. METHODS: 26 patients were examined at onset of aUPVD, and 3, 6 and 13 weeks later. To measure balance control and thereby assess the contribution of VSR influences during stance and gait, body-worn gyroscopes mounted at lumbar 1-3 recorded the angular velocity of the lower trunk in the roll (lateral) and pitch (anterior-posterior) directions. These signals were integrated to yield angle deviations. To measure VOR function, rotating chair (ROT) tests were performed with triangular velocity profiles with accelerations of 20 degrees /s(2) and 5 degrees /s(2), and caloric tests with bithermal (44 and 30 degrees C) water irrigation of the external auditory meatus. Changes in average balance and VOR measures at the 4 examination time points were modelled with exponential decays. Improvements were assumed to plateau when model values were to within 10% of steady state. RESULTS: Balance improvement rates were task and direction dependent, ranging from 3-9 weeks post aUPVD, similar to the range of ROT VOR improvement rates. Stance balance control improved similarly in the pitch and roll directions. Both reached steady state at 7.5 weeks. However, changes in visual and proprioceptive influences on stance sway velocities continued to decrease in favour of vestibular influences for over 10 weeks with the visual influence being correlated with ROT deficit side responses (R= 0.475). Spontaneous nystagmus and stance roll velocity were weakly correlated (R= 0.24). Pitch control during gait tests improved faster than roll. Gait speed was slower and only recovered normal velocity at 6-9 weeks. Pitch velocity when walking eyes closed was correlated (R= 0.38) with ROT asymmetry. Other balance and VOR measures were more weakly correlated (R< 0.2) even if these had similar improvement rates. CONCLUSIONS: These results indicate that balance control for stance improves equally fast in the pitch and roll directions. For gait, pitch control improves faster than roll. On average, stance and gait tests show normal balance control at 6-9 weeks post aUPVD onset. As few balance measures are correlated with those of VOR function and then with low (R< 0.5) coefficients, we suggest that VOR tests should not be used to assess improvements in balance control after aUPVD. The lack of strong correlations between balance and VOR measures included in this study during peripheral recovery and central compensation of aUPVD supports the hypothesis that recovery of balance function after an aUPVD involves different CNS pathways and neural plasticity mechanisms. PMID- 26890425 TI - Falls and fear of falling in vertigo and balance disorders: A controlled cross sectional study. AB - BACKGROUND: Vertigo and dizziness are among the most prevalent symptoms in neurologic disorders. Although many of these patients suffer from postural instability and gait disturbances, there is only limited data on their risk of falling. METHODS: We conducted a controlled cross-sectional study at the tertiary care outpatient clinic of the German Center for Vertigo and Balance Disorders using a self-administered questionnaire to assess falls, fall-related injuries, and fear of falling. The recruitment period was 6 months. RESULTS: A total of 569 patients (mean age 59.6 +/- 17.1 years, 55% females) and 100 healthy participants were included (response rate > 90%). Dizzy patients with central balance disorders (Parkinsonian, cerebellar, and brainstem oculomotor syndromes) had the highest fall rates (> 50% recurrent fallers, odds ratio > 10). The rate of recurrent fallers was 30% in bilateral vestibular failure and peripheral neuropathy (odds ratio > 5). Patients with functional dizziness (somatoform or phobic vertigo) were concerned about falling but did not fall more often than healthy controls (odds ratio 0.87). CONCLUSION: Falls are common in patients presenting to a dizziness unit. Those with central syndromes are at risk of recurrent and injurious falling. Fall rates and fear of falling should be assessed in balance disorders and used to guide the regimen of rehabilitation therapy. The identification of risk factors would help provide protective measures to these groups of patients. PMID- 26890424 TI - Retrospective data suggests that the higher prevalence of benign paroxysmal positional vertigo in individuals with type 2 diabetes is mediated by hypertension. AB - OBJECTIVE: Benign Paroxysmal Positional Vertigo (BPPV) has been linked to comorbidities like diabetes and hypertension. However, the relationship between type 2 diabetes (DM) and BPPV is unclear. The purpose of this retrospective study was to examine the relationship between DM and BPPV in the presence of known contributors like age, gender and hypertension. METHODS: A retrospective review of the records of 3933 individuals was categorized by the specific vestibular diagnosis and for the presence of type 2 DM and hypertension. As the prevalence of BPPV was higher in people with type 2 DM compared to those without DM, multivariable logistic regressions were used to identify variables predictive of BPPV. The relationship between type 2 DM, hypertension and BPPV was analyzed using mediation analysis. RESULTS: BPPV was seen in 46% of individuals with type 2 DM, compared to 37% of individuals without DM (p< 0.001). Forty two percent of the association between type 2 DM and BPPV was mediated by hypertension, and supported hypertension as a complete mediator in the relationship between type 2 DM and BPPV. CONCLUSIONS: Hypertension may provide the mediating pathway by which diabetes affects the vestibular system. Individuals with complaints of dizziness, with comorbidities including hypertension and diabetes, may benefit from a screening for BPPV. PMID- 26890426 TI - The activities-specific balance confidence scale and berg balance scale: Reliability and validity in Arabic-speaking vestibular patients. AB - Persons with vestibular disorders are susceptible to imbalance. The Activities specific Balance Confidence (ABC) scale and Berg Balance Scale (BBS) have been validated in persons with vestibular disorders. The purpose of this study was to examine the reliability and validity of the Arabic versions of ABC and BBS among Arabic-speaking persons with vestibular disorders in Jordan and Saudi Arabia. Therefore, the A-ABC and A-BBS were administered to a convenience sample of 82 persons with vestibular disorders (age = 43 +/- 14), (56% female). The test retest reliability of the A-ABC item and total score as well as the inter-rater and intra-rater reliability of the A-BBS total score reflected high agreement. Significant and large correlations were found between the A-ABC and the A-BBS (r= 0.54, P< 0.05), the A-ABC and the Arabic Dizziness Handicap Inventory (A-DHI) (r= -0.76, P< 0.05), and the A-BBS and the A-DHI (r= -0.56, P< 0.05). The A-ABC and the A-BBS demonstrated good reliability and validity and can be utilized with Arabic-speaking persons with vestibular disorders. PMID- 26890427 TI - Diagnostic value of vestibular-evoked myogenic potentials in Meniere's disease and vestibular migraine. AB - Overlaps can be seen between vestibular migraine (VM) Meniere's Disease (MD) and diagnosis is difficult if hearing is normal. We aimed to investigate the sacculo collic pathway in VM patients, MD patients, and healthy controls to define the diagnostic role of cervical VEMP (cVEMP). VEMP testing in response to 500 Hz and 1000 Hz air-conducted tone burst (TB) stimulation was studied prospectively in 22 subjects with definite VM (according to Barany nomenclature), 30 subjects with unilateral definite MD, and 18 volunteers matched healthy controls. In VM subjects, response rate, p13 and n23 latencies were similar to healthy controls, but peak-to-peak amplitudes were bilaterally reduced at 500 Hz TBs (p= 0.005). cVEMP differentiated MD patients from VM and healthy controls with asymmetrically reduced amplitudes on affected ears with low response rates at 500 Hz TBs, and alteration of frequency dependent responses at 500 and 1000 Hz TBs. These findings suggest that cVEMP can be used as a diagnostic test to differentiate MD from VM. On the other hand, VEMP responses are symmetrically reduced on both sides in VM patients, suggesting that otolith organs might be affected by migraine-induced ischemia. PMID- 26890428 TI - Anticompensatory quick eye movements after head impulses: A peripheral vestibular sign in spontaneous nystagmus. AB - BACKGROUND: Differentiating central from peripheral origins of spontaneous nystagmus (SN) is challenging. Looking for a simple sign of peripheral disease with the video Head Impulsive Test we noticed anti-compensatory eye movements (AQEM) in patients with peripheral etiologies of spontaneous nystagmus (SN). Here we assess the diagnostic accuracy of AQEM in differentiating peripheral from central vestibular disorders. METHODS: We recorded the eye movements in response to horizontal head impulses in a group of 43 consecutive patients with acute vestibular syndrome (12 with central, 31 with peripheral disorders), 5 patients after acute vestibular neurectomy (positive controls) and 39 healthy subjects (negative controls). AQEM were defined as quick eye movements (peak velocity above 50 degrees /s) in the direction of the head movement. RESULTS: All patients with peripheral disorders and positive controls had AQEM (latency 231 +/- 53 ms, amplitude 3.4 +/- 1.4 degrees , velocity 166 +/- 55 degrees /s) when their head was moved to the opposite side of the lesion. Central patients did not have AQEM. AQEM occurrence rate was higher in peripheral patients with contralesional (74 +/ 4%, mean +/- SD) in comparison to ipsilesional (1 +/- 4%) impulses (p< 0.001). Overall diagnostic accuracy for differentiating central from peripheral patients was 96% (95% CI for AUC ROC curve: 0.90 to 1.0) for VOR gain and 100% (95% CI: 1.0 to 1.0) for AQEM occurrence rate. CONCLUSIONS: These results suggest that AQEM are a sign of vestibular imbalance in a peripheral deficit. In addition to VOR gain they should be added to the evaluation of the head impulse test. PMID- 26890431 TI - The ties that bind: Maternal kin bias in a multilevel primate society despite natal dispersal by both sexes. AB - In many social animals, individuals derive fitness benefits from close social bonds, which are often formed among kin of the philopatric sex. Hamadryas baboons, however, exhibit a hierarchical, multilevel social system where both sexes disperse from their natal one-male-unit (OMU). Although this would seem to hinder maintenance of kin ties, both sexes appear largely philopatric at the higher order band and clan levels, possibly allowing for bonds with same sex kin by both males and females. In order to investigate the possibility of kin bonds in hamadryas baboons, we identified kin dyads in a band without known pedigree information using a large panel of genetic markers: 1 Y-linked, 4 X-linked, and 23 autosomal microsatellites and part of the mitochondrial hypervariable region I. With these data, we performed a kinship analysis while accounting for misclassification rates through simulations and determined kinship among two types of dyads: leader and follower males and female dyads within OMUs. Leader and follower males were maternal relatives more often than expected by chance, suggesting that kinship plays a role in the formation of these relationships. Moreover, maternal female relatives were found in the same OMU more often than expected by chance, indicating that females may be motivated to maintain post dispersal contact with maternal female kin. Our results suggest that hamadryas baboons can recognize maternal kin and that kin selection has contributed to shaping their complex social system. This implies that an ancestral maternal kin bias has been retained in hamadryas society. Am. J. Primatol. 78:731-744, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890432 TI - The effects of acupuncture point Pericardium 6 on hydromorphone-induced nausea and vomiting in healthy dogs. AB - OBJECTIVE: To evaluate the effect of needling at acupuncture point Pericardium 6 on hydromorphone-induced nausea and vomiting. STUDY DESIGN: Randomized controlled clinical study. ANIMALS: Eighty-one mixed-breed, healthy dogs aged 1.8 +/- 1.6 years and weighing 14.5 +/- 5.6 kg, admitted for elective ovariohysterectomy (n = 75) or castration (n = 6). METHODS: Dogs were randomly assigned to one of three groups: acupuncture at Pericardium 6 (AT, n = 27); alternative acupuncture at Lung 5 (ST, n = 27), and no acupuncture (CT, n = 27). During time 0-30 minutes (baseline), occurrences of hypersalivation, vomiting and licking were recorded. At 30 minutes, subjects were administered hydromorphone (0.1 mg kg(-1) ) in combination with acepromazine (0.03 mg kg(-1) ) intramuscularly. During time 30 45 minutes (post-injection), occurrences of hypersalivation, vomiting and licking were recorded by an observer unaware of group assignment. Groups were compared using a Kruskal-Wallis test followed by a Dunn's post-test, or Fisher's exact tests when appropriate. RESULTS: There were no significant differences in age, weight or baseline observations among groups. Vomiting incidence post-injection was higher in the CT (20/27, 74.1%) and ST (22/27, 81.5%) groups than in the AT (10/27, 37.0%) group (p = 0.0129 and p = 0.002, respectively). The number of vomiting episodes [median (range)] after opioid administration was higher in the ST [1 (1-6)] than the AT [0 (0-2)] group (p = 0.0040). There were no differences in the median number of vomiting episodes between the ST and CT [1 (0-3)] or AT and CT groups. There were no differences in hypersalivation or licking among groups after hydromorphone-acepromazine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Pericardium 6 acupuncture reduced the incidence of hydromorphone induced vomiting in healthy dogs. This cost-effective technique can improve patient well-being and comfort during the perioperative period. PMID- 26890433 TI - Evidence for Vertical Transmission of Novel Duck-Origin Goose Parvovirus-Related Parvovirus. AB - In 2015, novel duck-origin goose parvovirus-related parvovirus (N-GPV) infection progressively appeared in commercial Cherry Valley duck flocks in North China. Diseased ducks were observed to have beak atrophy and dwarfism syndrome (BADS). A previous study showed that a high seropositive rate for N-GPV indicated a latent infection in most breeder duck flocks. To investigate this possibility in hatching eggs collected from N-GPV-infected breeder ducks, 120 eggs were collected at various stages of embryonic development for viral DNA detection and an N-GPV-specific antibody test. N-GPV DNA was present in nine hatching eggs, eleven duck embryo and eight newly hatched ducklings. Of the newly hatched ducklings, 58.33% (21/36) were seropositive. Further, two isolates were obtained from a 12-day-old duck embryo and a newly hatched duckling. N-GPV infection did not reduce the fertilization rate and hatchability. These results indicate possible vertical transmission of N-GPV and suggest that it may be transmitted from breeder ducks to ducklings in ovo. PMID- 26890434 TI - Seeing Their Children in Pain: Symptoms of Posttraumatic Stress Disorder in Mothers of Children with an Anomaly Requiring Surgery at Birth. AB - Objective Assess the presence of posttraumatic stress disorder (PTSD) symptoms in mothers of newborns requiring early surgery. Study Design Mothers of newborns operated on for a congenital anomaly underwent a semi-structured interview on their experience 6 months postpartum. Interviews were audiotaped, transcribed verbatim, and analyzed for symptoms of the three major criteria of PTSD: re experiencing, avoidance, and heightened arousal. Results A total of 120 mothers took part in the study; their children were affected by one of the following congenital anomaly: esophageal atresia (n = 29); congenital diaphragmatic hernia (n = 38); midgut malformations (n = 38); and abdominal wall defects (n = 15). Two mothers did not show any symptoms; 12 mothers (10%) had one posttraumatic symptom, 77 (64.2%) had two, and 29 (24.2%) had three. Overall, 106 mothers (88.4%) presented at least two symptoms. Conclusion PTSD can be considered a useful model to describe and comprehend mothers' reactions in this specific population. Preventive interventions and dedicated follow-up program should be offered to these families. PMID- 26890435 TI - Persistence of Neonatal Brachial Plexus Palsy Associated with Maternally Reported Route of Delivery: Review of 387 Cases. AB - Objective The factors associated with persistent neonatal brachial plexus palsy (PNBPP) are unknown. Our objectives are to compare PNBPP at 1 and 2 years in children delivered via vaginal delivery (VD) versus cesarean delivery (CD) and in children delivered via VD with or without reported shoulder dystocia (SD). Study Design Retrospective cohort of children diagnosed with neonatal brachial plexus palsy (NBPP). Maternally reported delivery history and presence of SD were recorded with Student t-test, chi-square test, and odds ratio (OR) with 95% confidence intervals (CI) calculated for comparisons. Results Of 387 cases of NBPP, 8% (30) delivered via CD. Rates of PNBPP were higher in the VD group at 1 and 2 years (60% of CD and 85% of VD; OR, 0.26; 95% CI, 0.11-0.62 at 1 year; 33% of CD and 73% of VD; OR, 0.15; 95% CI, 0.05-0.39 at 2 years). There was no difference in PNBPP in women with VD with or without maternally reported SD (87 vs. 85%, p = 0.68 at 1 year; 64 vs. 61%, p = 0.61 at 2 years). Conclusion PNBPP is possible with CD, and there is no difference in PNBPP in VD with or without maternally reported SD. A prospective study is warranted to ascertain associative factors. PMID- 26890436 TI - Impact of Early Screening for Gestational Diabetes on Perinatal Outcomes in High Risk Women. AB - Objective To examine the benefits of early gestational diabetes mellitus (GDM) screening in a high-risk population. Study Design Retrospective cohort of all singletons diagnosed with GDM with indications for early screening: GDM or macrosomia in a prior pregnancy or obesity. Subjects were classified as early (<20 weeks) or routine (>24 weeks) screening. Patients diagnosed with GDM were managed according to standard institutional protocols. Outcomes examined were cesarean delivery (CD), preeclampsia, large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm birth (PTB). Results Subjects screened early were more likely to have had GDM in a prior pregnancy, hypertension, higher body mass index, and higher fasting glucose. Early and routine screening groups had similar incidences of CD (adjusted odds ratio [AOR] 0.95, 95% confidence interval [CI] 0.55-1.64), preeclampsia (AOR 0.84, 95% CI 0.38-1.83), LGA (AOR 0.90, 95% CI 0.51-1.72), SGA (AOR 0.38, 95% CI 0.13-1.13), and macrosomia (AOR 1.00, 95% CI 0.53-1.87). Subjects in the early screening group had a higher incidence of PTB (AOR 1.79, 95% CI 1.08-2.99). Conclusion We did not detect a benefit to early screening for women who met the criteria. The utility of early GDM screening requires evaluation in a prospective trial. PMID- 26890437 TI - Estimating Length of Stay by Patient Type in the Neonatal Intensive Care Unit. AB - Objective Develop length of stay prediction models for neonatal intensive care unit patients. Study Design We used data from 2008 to 2010 to construct length of stay models for neonates admitted within 1 day of age to neonatal intensive care units and surviving to discharge home. Results Our sample included 23,551 patients. Median length of stay was 79 days when birth weight was < 1,000 g, 46 days for 1,000 to 1,500 g, 21 days for 1,500 to 2,500 g, and 8 days for >=2,500 g. Risk factors for longer length of stay varied by weight. Units with shorter length of stay for one weight group had shorter lengths of stay for other groups. Conclusion Risk models for comparative assessments of length of stay need to appropriately account for weight, particularly considering the cutoff of 1,500 g. Refining prediction may benefit counseling of families and health care systems to efficiently allocate resources. PMID- 26890438 TI - Rate of Gestational Diabetes Mellitus and Pregnancy Outcomes in Patients with Chronic Hypertension. AB - Objective This study aims to determine the rate of gestational diabetes mellitus (GDM) in pregnancies complicated by chronic hypertension and to compare the adverse outcomes in chronic hypertensive pregnancies with and without GDM. Study Design A secondary analysis from a multicenter trial of low-dose aspirin for preeclampsia prevention in women with chronic hypertension. The rate of GDM was evaluated among singleton pregnancies complicated with chronic hypertension and grouped according to their GDM status. Pregnancy outcomes and rates of preterm delivery < 35 weeks and < 32 weeks, preeclampsia, indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death were compared between those with and without GDM. A subgroup analysis comparing women who developed superimposed preeclampsia with and without GDM was studied. Multivariate logistic-regression analysis was used to adjust for potentially confounding factors. Results A total of 763 women met the inclusion criteria: 129 (17%) developed GDM. Parity, race, maternal baseline blood pressure, antihypertensive drug use, and assignment to low-dose aspirin were not significantly different between the groups with and without GDM. Using univariate analysis, maternal age (33 vs. 24%, p = 0.03) and body mass index (88 vs. 57%, p < 0.001) were higher in those who had GDM, whereas the rate of preterm delivery < 32 weeks (12 vs. 5%, p = 0.02) was higher among those without GDM. Using logistic regression analysis, the rate of composite adverse outcomes (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.41-1.47) that included indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death showed no significant differences.Superimposed preeclampsia developed in 34 (26%) women with GDM and in 182 (29%) without GDM. When superimposed preeclampsia was present, it developed at an earlier gestational age among the group without GDM (35 +/- 5 vs. 37 +/- 3 weeks, p = 0.003), and had higher rates of small for gestational age infants (18 vs. 3%, p = 0.03). After adjustment for confounders, only length of stay in neonatal intensive care unit was longer for those without GDM who developed superimposed preeclampsia (aOR, 0.42; 95% CI, 0.2-0.93). Conclusion Women with chronic hypertension are at a high risk for developing GDM. Outcomes in patients with chronic hypertension and GDM are not significantly different from those with chronic hypertension only. PMID- 26890439 TI - Maternal Education Level Predicts Cognitive, Language, and Motor Outcome in Preterm Infants in the Second Year of Life. AB - Objective To evaluate the relative impact of maternal education level (MEL) on cognitive, language, and motor outcomes at 20 months' corrected age (CA) in preterm infants. Study Design A total of 177 preterm infants born between 2008 and 2010 were tested at 20 months' CA using the Bayley Scales of Infant and Toddler Development-III. Multiple regression analyses were done to determine the relative impact of MEL on cognitive, language, and motor scores. Results Infants born to mothers with high school MEL were 3.74 times more likely to have a subnormal motor index, while those born to mothers with some college and graduate school MEL had reduced odds (0.36 and 0.12, respectively) of having subnormal language index at 20 months. In linear regression, MEL was the strongest predictor of cognitive, language, and motor scores, and graduate school MEL was associated with increases in cognitive, motor, and language scores of 8.49, 8.23, and 15.74 points, respectively. Conclusions MEL is the most significant predictor of cognitive, language, and motor outcome at 20 months' CA in preterm infants. Further research is needed to evaluate if targeted interventions that focus on early childhood learning and parenting practices can ameliorate the impact of low MEL. PMID- 26890440 TI - Treatment Utility of Postpartum Antibiotics in Chorioamnionitis Study. AB - Objective To determine if postpartum antibiotics are necessary for patients with chorioamnionitis after a cesarean delivery (CD). Study Design Multicenter randomized controlled trial. Laboring patients with singleton gestations and chorioamnionitis who underwent CD were eligible. Patients were treated with ampicillin and gentamicin per standard protocol, then given clindamycin prior to skin incision. Patients were randomized to either postpartum antibiotic prophylaxis or no treatment following delivery. The primary outcome was the rate of endometritis. Assuming a 30% risk of endometritis in patients with chorioamnionitis who undergo CD, 119 patients per arm would be required to detect a 50% decrease in endometritis. Results The trial was stopped for futility following a planned interim analysis after 80 patients were randomized. There was no difference in the rate of the primary outcome between the two groups (9.8 vs. 7.7%, relative risk [RR]: 1.27; 95% confidence interval [CI]: 0.30, 5.31). A meta analysis comparing post-CD antibiotics versus no treatment did not find a statistically significant difference between the groups (16.7 vs. 12.0%, pooled RR: 1.43; 95% CI: 0.72, 2.84). Conclusion Additional postpartum antibiotics do not decrease the rate of endometritis in patients with chorioamnionitis who undergo CD. The current preoperative antibiotic regimen including clindamycin should remain the standard of care in these patients. PMID- 26890441 TI - Trends and Variations in the Use of Inhaled Nitric Oxide in Preterm Infants in Canadian Neonatal Intensive Care Units. AB - Objective To determine the proportion of infants who receive inhaled nitric oxide (iNO), and to characterize the variations in its use by gestational age (GA) and center in infants <34 weeks' gestation. Design Retrospective analysis was performed in infants born at <34 weeks' gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network between January 2010 and December 2013. Results Of 19,525 infants, 831 (4.2%) received iNO. A total of 369 infants (44%) received iNO during the first 2 days after birth. The proportion of neonates who received iNO in the 22 to 25, 26 to 29, and 30 to 33 weeks' GA groups was 16.1, 6.0, and 1.3%, respectively. Infants in whom iNO was initiated in the first 2 days of age received it for a shorter duration (median, 3 days; interquartile range [IQR], 2-5) as compared with those who started after 2 days (median, 5 days; IQR, 2-11). The use of iNO varied by center, ranging from 0 to 15.5% (p < 0.001). Conclusion Out of every 25 infants born at <34 weeks' gestation in Canada received iNO, with the highest rate of use in infants born at lower gestation. Further research to identify reasoning, efficacy, and safety of iNO in preterm infants is warranted. PMID- 26890442 TI - IL-1beta (interleukin-1beta) stimulates the production and release of multiple cytokines and chemokines by human preadipocytes. AB - The effect of IL-1beta on cytokine and chemokine production by human preadipocytes has been examined. Preadipocytes were incubated with IL-1beta, and cytokine and chemokine release was measured at 24 h by protein arrays, while the expression of cytokine/chemokine genes was assessed by qPCR at 4 and 24 h. IL 1beta stimulated the secretion of multiple cytokines/chemokines, including IL-6, IL-8, IL-10, IL-13, MCP-4, TNFalpha and IP-10. IL-10 was not released by un stimulated preadipocytes, while IL-6 exhibited the greatest response to IL-1beta (453-fold increase). IL-16 and IL-12p40 did not respond to IL-1beta. qPCR demonstrated that IL-1beta markedly stimulated CCL3, CSF3 and CXCL10 expression at 4 h (>900-fold mRNA increase). A time-course indicated that while CCL13 (encoding MCP-4) exhibited minimal basal expression in preadipocytes, expression increased progressively following differentiation. Human preadipocytes are highly sensitive to IL-1beta, the cytokine stimulating a major inflammatory response in these cells similar to that in mature adipocytes. PMID- 26890445 TI - John Porter Lecture: Liberal Nationalisms Revisited. AB - Liberal Nationalisms: Empire, State and Civil Society in Scotland and Quebec argues that the emergence and character of nationalism are directly related to changes in patterns of political rule and the liberal settlements that underlay that rule. The focus is on the emergence of two nationalist groups in Scotland and Quebec at the beginning of the twentieth century: the Young Scots' Society and Ligue nationaliste canadienne. They exhibited liberal nationalisms differently (1) in response to the British Empire's predatory imperial policies, (2) in the perception that their states had failed to effectively accommodate the Scottish and French Canadian nations, and more problematically (3) on the place of organized religion in civil society. Their responses suggest the emergence of two quite distinct liberal nationalisms: one in which the emphasis was on universal individual rights, and the other in which particular group rights were more clearly favored. The article offers some further reflection on the relationship between nationalism and liberalism, specifically on the existence of a symbiotic relationship and more generally that liberalism is successful when embedded in nationalism. PMID- 26890443 TI - Detection of beta-Thalassemia Mutations Using TaqMan Single Nucleotide Polymorphism Genotyping Assays. AB - AIMS: Sickle-cell anemia and beta-thalassemia are two of the most common autosomal recessive disorders in the developing world. The severity of the problem and the pressure it exerts on the health services in the Kingdom of Saudi Arabia forced the introduction of a national premarital screening program to lessen its impact on the society. Furthermore, a significant effort has been exerted in the elucidation of the genetic causes of such diseases to facilitate diagnosis and detection of carriers. METHODS: We have designed and validated the use of custom TaqMan((r)) genotyping assays for the rapid detection of IVS-I-1 (G>A), IVS-I-5 (G>C), codon 39 (C>T), and IVS-I-110 (G>A) mutations in transfusion-dependent beta-thalassemia patients' cohort. RESULTS: We demonstrated that IVS-I-5 (rs33915217) is the most common single-nucleotide variant in our cohort, with the variant allele constituting 26% of the total alleles investigated. However, this variant was not found in 352 alleles screened from buccal swab DNA obtained from healthy volunteers. CONCLUSION: The TaqMan single nucleotide polymorphism (SNP) genotyping assays are a rapid, accurate, and cost effective method for the initial screening of beta-thalassemia cases, which will minimize the need for direct sequencing of the HBB gene, thus reducing detection costs and increasing throughput. PMID- 26890446 TI - "More Normal than Welfare": The Mincome Experiment, Stigma, and Community Experience. AB - This paper examines the impact of a social experiment from the 1970s called the Manitoba Basic Annual Income Experiment (Mincome). I examine Mincome's "saturation" site located in Dauphin, Manitoba, where all town residents were eligible for guaranteed annual income payments for three years. Drawing on archived qualitative participant accounts I show that the design and framing of Mincome led participants to view payments through a pragmatic lens, rather than the moralistic lens through which welfare is viewed. Consistent with prior theory, this paper finds that Mincome participation did not produce social stigma. More broadly, this paper bears on the feasibility of alternative forms of socioeconomic organization through a consideration of the moral aspects of economic policy. The social meaning of Mincome was sufficiently powerful that even participants with particularly negative attitudes toward government assistance felt able to collect Mincome payments without a sense of contradiction. By obscuring the distinctions between the "deserving" and "undeserving" poor, universalistic income maintenance programs may weaken social stigmatization and strengthen program sustainability. PMID- 26890447 TI - What Gets Covered? An Examination of Media Coverage of the Environmental Movement in Canada. AB - This article analyzes press releases from the World Wildlife Fund (WWF) and Greenpeace (GP) to assess how their tactics and frames affect the amount of coverage they receive in The Globe and Mail and National Post from 2000 to 2010. While it is clear that some tactics are more likely to garner media coverage, the full range of tactics and frames are not effective for all groups. For example, calling to the public to engage in a social issue leads to increased media coverage for GP but not WWF. And, using research does not affect media coverage for WWF, but decreases coverage for GP. This study demonstrates that the effect of tactical choices on media coverage is contingent on the identity of the group using them. PMID- 26890448 TI - Motherhood as a Gendered Entitlement: Intentionality, "Othering," and Homosociality in the Online Infertility Community. AB - Motherhood is one of the most enduring rites of passage to adult femininity for women. However, not all women have access to motherhood. In this paper, I explore the online infertility community wherein women blog to process their exclusion, expressing incredulity about the prospect of never having a biological child of their own. Women understand their infertility as an injustice, leading them to lay claim to motherhood. I argue that how women lay claim to motherhood changes our understanding of motherhood as a gendered norm. Motherhood is more than a pursuit of a gender identity; it is also a gendered entitlement. This research pushes analytic conceptualizations of motherhood forward, while also empirically enriching our knowledge about women's homosociality. PMID- 26890449 TI - What the Polls Do Show: Toward Enhanced Survey Readings of Religion in Canada. AB - Over the past two decades or so, survey research findings on religious activities and beliefs have been confusing, with the results of researchers and private pollsters frequently differing from those of Statistics Canada. In this research note, the authors use four national omnibus surveys conducted in 2012 to explore the extent to which such differences are due to measurement variations. Finding few noteworthy differences, they proceed to focus on the samples being used, and draw on illustrative data from 2012 and 2015 to argue that the differences in findings may in large part be due to differences in samples. The resolution of sampling problems, they acknowledge, is extremely difficult, but nonetheless is a goal that has to be pursued. PMID- 26890450 TI - Generation of Zerovalent Metal Core Nanoparticles Using n-(2-aminoethyl)-3 aminosilanetriol. AB - In this work, a facile one-pot reaction for the formation of metal nanoparticles in a water solution through the use of n-(2-aminoethyl)-3-aminosilanetriol is presented. This compound can be used to effectively reduce and complex metal salts into metal core nanoparticles coated with the compound. By controlling the concentrations of salt and silane one is able to control reaction rates, particle size, and nanoparticle coating. The effects of these changes were characterized through transmission electron microscopy (TEM), UV-Vis spectrometry (UV-Vis), Nuclear Magnetic Resonance spectroscopy (NMR) and Fourier Transform Infrared spectroscopy (FTIR). A unique aspect to this reaction is that usually silanes hydrolyze and cross-link in water; however, in this system the silane is water soluble and stable. It is known that silicon and amino moieties can form complexes with metal salts. The silicon is known to extend its coordination sphere to form penta- or hexa-coordinated species. Furthermore, the silanol group can undergo hydrolysis to form a Si-O-Si silica network, thereby transforming the metal nanoparticles into a functionalized nanocomposites. PMID- 26890451 TI - Implementation of the 21-gene recurrence score test in the United States in 2011. AB - PURPOSE: We examined hospital use of the 21-gene breast cancer test in the United States. We report state-level differences in utilization and propose a model for predicting implementation of guideline-recommended genomic testing. METHODS: Genomic Health provided test orders for calendar year 2011.We summarized utilization at the hospital and state levels. Using logistic regression, we analyzed the association between the likelihood to order the test and the hospital's institutional and regional characteristics. RESULTS: In 2011, 45% of 4,712 acute-care hospitals ordered the test, which suggests that 25% of newly diagnosed invasive female breast cancer cases were tested. Significant predictors of testing included participation in National Cancer Institute (NCI) clinical research cooperative groups (odds ratio (OR) 3.73; 95% confidence interval, 2.96 4.70), advanced imaging (OR, 2.19; CI, 1.78-2.68), high-complexity laboratory (OR, 2.15; CI, 1.24-3.70), affiliation with a medical school (OR, 1.57; CI, 1.31 1.88), and reconstructive surgery (OR, 1.23; CI, 1.01-1.50). Significant regional predictors included metropolitan county (OR, 3.77; CI, 2.83-5.03), above-mean income (OR, 1.37; CI, 1.11-1.69), and education (OR, 1.26; CI, 1.03-1.54). Negative predictors included designation as a critical-access hospital (OR, 0.10; CI, 0.07-0.14) and distance from an NCI cancer center (OR, 0.998; CI, 0.997 0.999), with a 15% decrease in likelihood for every 100 miles. CONCLUSION: Despite considerable market penetration of the test, there are significant regional and site-of-care differences in implementation, particularly in rural states.Genet Med 18 10, 982-990. PMID- 26890453 TI - Recontact in clinical practice: a survey of clinical genetics services in the United Kingdom. AB - PURPOSE: To ascertain whether and how recontacting occurs in the United Kingdom. METHOD: A Web-based survey was administered online between October 2014 and July 2015. A link to the survey was circulated via an e-mail invitation to the clinical leads of the United Kingdom's 23 clinical genetics services, with follow up with senior clinical genetics staff. RESULTS: The majority of UK services reported that they recontact patients and their family members. However, recontacting generally occurs in an ad hoc fashion when an unplanned event causes clinicians to review a file (a "trigger"). There are no standardized recontacting practices in the United Kingdom. More than half of the services were unsure whether formalized recontacting systems should be implemented. Some suggested greater patient involvement in the process of recontacting. CONCLUSION: This research suggests that a thorough evaluation of the efficacy and sustainability of potential recontacting systems within the National Health Service would be necessary before deciding whether and how to implement such a service or to create guidelines on best-practice models.Genet Med 18 9, 876-881. PMID- 26890452 TI - Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations. AB - PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism's fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well.Genet Med 18 10, 1029-1036. PMID- 26890454 TI - The Use of Piezosurgery in Genioplasty. AB - The aim of this study was to compare the postoperative complications during genioplasty using piezosurgery devices or traditional rotating drills. Forty patients underwent genioplasty to solve their chin anomalies. This study showed that, using piezosurgery, pain and swelling were reduced compared to the traditional technique in the immediate postoperative period of healing (within 15 days). Paresthesia was observed in all patients up to 15th postoperative day, independently of the used surgical technique, but at the sixth postoperative month it was completely absent. PMID- 26890455 TI - Synthesis of the New-Type Vascular Endothelial Growth Factor-Silk Fibroin Chitosan Three-Dimensional Scaffolds for Bone Tissue Engineering and In Vitro Evaluation. AB - The objective of the study was to discuss the biocompatibility of the vascular endothelial growth factor-silk fibroin-chitosan (VEGF-SF-CS) scaffolds. To offer an ideal scaffold for bone tissue engineering, the author added vascular endothelial growth factor (VEGF) into silk fibroin-chitosan (SF-CS) scaffold directly to reconstruct a three-dimensional scaffold for the first time, SF-CS scaffold was loaded with VEGF and evaluated as a growth factor-delivery device. Human fetal osteoblast cell was seeded on the VEGF-SF-CS scaffolds and SF-CS scaffolds. On VEGF-SF-CS and SF-CS scaffolds, the cell adhesion rate was increased as time went on. Scanning electron microscopy: the cells grew actively and had normal multiple fissions, granular and filamentous substrates could be seen around the cells, and cell microfilaments were closely connected with the scaffolds. The cells could not only show the attached growth on surfaces of the scaffolds, but also extend into the scaffolds. Cell Counting Kit-8 and alkaline phosphatase analysis proved that the VEGF could significantly promote human fetal osteoblast1.19 cells growth and proliferation in the SF-CS scaffolds, but the enhancement of osteoblasts cell proliferation and activity by VEGF was dependent on time. PMID- 26890456 TI - Navigation-Assisted Bone Grafting for Blowout Fracture. AB - BACKGROUND: Treatment of orbital floor fracture accompanied by extensive bone defect requires orbital floor reconstruction using a bone graft, but graft may deviate into the maxillary sinus when no bone capable of supporting the graft remains around the defect. In such cases, it is necessary to fix the grafted bone to the orbital margin, but the grafted bone placement site is subjectively decided based on inspection through a small incision in many cases, being dependent on the experience of operators, and it has been difficult to accurately determine the placement angle. METHODS: The authors applied a navigation system in 4 patients with orbital blowout fracture, and evaluated for the exact bone graft placement angle and orbital floor form during surgery. RESULTS: The bone graft placement angle was evaluated by comparison with a mirror image of the nonaffected side. The angle could be confirmed during surgery, as well as the lateral symmetry of the orbital form. On postoperative computed tomography, the grafted bone was retained at a favorable placement site. CONCLUSIONS: The navigation system may be useful to support the treatment of orbital blowout fracture, as it facilitates safe dissection around orbital floor bone defects, confirmation of the positional relationship between the bone fragment and orbital tissue and bone graft fixation position, and evaluation of lateral symmetry of the orbital floor form during surgery. PMID- 26890457 TI - Evaluation of Volumetric Changes of Augmented Maxillary Sinus With Different Bone Grafting Biomaterials. AB - Extensive alveolar bone resorption because of pneumatized maxillary sinus is a common problem that limits dental implant placement. Maxillary sinus floor augmentation (MSFA) is an accepted treatment protocol that provides sufficient bone volume. The aim of this study was to evaluate the percentage of graft volume reduction following MSFA using cone beam computed tomography. In this retrospective study, cone beam computed tomography scans of MSFA were measured to evaluate the volume of the grafted sinus with deproteinized bovine bone (DBB), mineralized allograft (MA), or a mixture of MA and demineralized allograft as a composite. The volumetric changes in sinus augmentation between 2 weeks (T-I) and 6 months (T-II) after operation were analyzed. Thirty-nine patients were included in this study. The average percent volume reduction was 8.14 +/- 3.76%, 19.38 +/- 9.22%, and 24.66 +/- 4.68% for DBB, MA, and composite graft, respectively. A significant graft volume reduction was found between T-I and T-II for all groups (P < 0.01). The DBB group showed the least volume reduction (P < 0.01). Biomaterials can influence the bone graft volume change before implant placement. Deproteinized bovine bone may offer greater volume stability during healing than mineralized and composite allografts. PMID- 26890458 TI - Craniosynostosis Following Fetal Methotrexate Exposure. AB - Methotrexate (MTX) is an antimetabolite, folic acid antagonist that inhibits purine nucleotide production, DNA synthesis, and cellular proliferation. Despite widespread therapeutic uses, MTX remains a potent teratogen. Methotrexate embryopathy encompasses multiorgan system dysfunction, including intrauterine growth restriction as well as cardiac, craniofacial, renal, genital, and skeletal abnormalities. Effects of MTX exposure on fetal development continue to be described. This series of 4 patients with MTX-associated craniosynostosis represents the largest published association between prenatal MTX exposure and premature cranial suture closure. PMID- 26890459 TI - Study of Genial Tubercles of Craniofacial Anomalies Individuals on Cone Beam Computed Tomography Scans. AB - PURPOSE: Genial tubercles (GTs) are bony protuberances on the lingual aspect of the mandible symphysis, where genioglossus and geniohyoid muscles are inserted. In the literature, few papers report their real dimensions. Cleft lip and palate are craniofacial anomalies involving the maxilla, but the anatomical structures of the mandible can be altered when these have associated with the cleft, some syndrome. This study aimed to evaluate the GTs of 30 individuals and to make their measurements in cone beam computed tomography examinations. METHODS: A sample of 30 individuals, 19 of them with cleft lip and palate, 6 individuals with Treacher Collins syndrome (TCS), and 5 individuals with Pierre Robin sequence, was used. The GTs were evaluated about the amount and the following measurements were performed: A--distance from the apex of the central incisors to GT, B--mandibular thickness in the region of GT, C-GT height, D-GT width, and E- distance from inferior border of mandible to GT. RESULTS: The individuals presented since the absence of GTs to 3. The TCS group had the highest average of the measurements A, D, and E with statistical difference (P = 0.006) (P = 0.011) and (P = 0.017), respectively. The Pierre Robin sequence group had the highest average measurement of B and C, but there was no statistical difference. CONCLUSIONS: The difference in the measurements can be explained perhaps because individuals with TCS have glossoptosis and changes on retrognathic mandible, which would affect the position of the GT. PMID- 26890460 TI - Orthognathic Surgery in Patients With Large Condylar Destructions. AB - Condylar resorption is understood as changes in shape and volume of the condylar bone, due to local, systemic, and iatrogenic factors. The occurrence of condylar resorption after orthognathic surgery can occur when the condylar repositioning in mandibular fossa is performed improperly. In addition, systemic diseases such as osteoarthritis and rheumatoid arthritis seem to influence this process. The aim of this study was to report 3 cases of patients with severe condylar alterations, submitted to orthognathic surgery for treatment of dentofacial deformities. Considerations regarding the diagnosis, surgical planning (counterclockwise rotation), surgical techniques (bilateral sagittal split osteotomy, bimaxillary osteotomies, rigid fixation, maxillomandibular fixation period), and results (short terms) are discussed. PMID- 26890461 TI - A Huge Ancient Schwannoma of the Epiglottis. AB - Ancient schwannoma of the epiglottis is extremely rare. The authors report the first case of a patient with a huge ancient schwannoma of the epiglottis. Clinicians should consider the possibility that ancient schwannoma may originate in the epiglottis mimicking the other more frequently observed lesions. PMID- 26890462 TI - Anteriorly Based Galeo-Pericranial Frontalis Flap: A Novel Application in Secondary Rhinoplasty With Atrophic Skin. AB - BACKGROUND: Nasomaxillary dysplasia (Binder syndrome) and cleft are congenital malformations of the midface. Ideally, the nasal deformity is treated from childhood. This approach leads to the need for several surgeries and revisions until full growth is reached. As a result of multiples procedures, the skin over the nasal dorsum sometimes becomes thin, atrophic and could be strongly attached to underlying grafts. For this setting of patients when another rhinoplasty is required, it becomes a technical challenge. The authors describe their experience in complex secondary rhinoplasty performed in patients with thin atrophic skin using the anteriorly based galeo-pericranial frontalis flap (GPFF) to improve the quality of the covering soft tissue along the whole nose skeleton area. RESULTS: Since 2013, 3 female patients; 2 of them with Binder syndrome and 1 cleft lip/palate patient (average 18 years) with previous rhinoplasty (3-6 procedures) are subjected to secondary rhinoplasty using GPFF turning it over the osteochondral nasal framework. Postoperative follow-up was 3 to 18 months. There were no viability complications of the dorsum skin flap in the immediate postoperative period. At long-term follow-up, a visible improvement of local skin conditions and restoration of the nasal contour was achieved. CONCLUSIONS: The anteriorly based GPFF is a well-vascularized versatile flap used extensively in anterior cranial fossa surgery and frontal sinus trauma. Given its known and constant vascular anatomy, this flap is adapted to a new application in complex secondary rhinoplasty, in the presence of atrophic skin with good aesthetic outcomes. PMID- 26890463 TI - Enhanced Electron Transfer Reactivity of a Nonheme Iron(IV)-Imido Complex as Compared to the Iron(IV)-Oxo Analogue. AB - Reactions of N,N-dimethylaniline (DMA) with nonheme iron(IV)-oxo and iron(IV) tosylimido complexes occur via different mechanisms, such as an N-demethylation of DMA by a nonheme iron(IV)-oxo complex or an electron transfer dimerization of DMA by a nonheme iron(IV)-tosylimido complex. The change in the reaction mechanism results from the greatly enhanced electron transfer reactivity of the iron(IV)-tosylimido complex, such as the much more positive one-electron reduction potential and the smaller reorganization energy during electron transfer, as compared to the electron transfer properties of the corresponding iron(IV)-oxo complex. PMID- 26890464 TI - Quality of care metrics in chronic hepatitis B. PMID- 26890465 TI - Nationwide and population-based prescription patterns in bipolar disorder. AB - OBJECTIVES: The aim of the present study was to describe prescription patterns and changes in these patterns over the last decade for patients diagnosed with bipolar disorder in mental healthcare, using population-based and nationwide data, and to relate the findings to recommendations from international guidelines. METHODS: A population-based, nationwide study was carried out. It included register-based longitudinal data on all patients with a first-ever contact with mental healthcare with a diagnosis of mania/bipolar disorder from the entire Danish population, and all prescription data for this population during the decade from 2000 to 2011, inclusive. RESULTS: A total of 3,205 patients were included in the study. Lithium was prescribed less, and antiepileptic and atypical antipsychotic agents were prescribed substantially more during the study period. Lithium went from being the first drug prescribed to being the last, and was replaced by atypical antipsychotic agents. Antiepileptic agents went from being the fourth to the second drug class prescribed, and the prescription of antidepressants was virtually unchanged, at a high level, during the decade (one-year value 40-60%). The prescription of lamotrigine and quetiapine increased substantially. Combination therapy increased for all drug combinations, except for lithium combined with antidepressants. CONCLUSIONS: Major changes took place in drug prescriptions during the study period. The decrease in the use of lithium and the constant high use of antidepressants do not align with recommendations from international guidelines. PMID- 26890467 TI - RETRACTION. PMID- 26890468 TI - Muscle strength, mobility, quality of life and falls in patients on maintenance haemodialysis: A prospective study. AB - AIM: The aim is to explore (i) the relationship between quality of life and physical parameters (muscle strength and mobility) among people undergoing maintenance haemodialysis; (ii) changes in strength and mobility over time and predictors of changes; and (iii) whether strength and mobility were associated with falls. METHODS: We recruited 51 maintenance haemodialysis patients to a prospective longitudinal study. Baseline quality of life was assessed using the SF-36 physical component summary and mental component summary scores. Muscle strength (ankle dorsiflexion strength measured with a hand-held dynamometer), mobility (short physical performance battery) and falls history were assessed at baseline, 12 and 36 months. Associations between variables at baseline were assessed with linear regression models. Changes in physical parameters were evaluated with paired t-tests and prediction of falls assessed by negative binominal regression. RESULTS: Fifty and 34 patients completed 12 and 36 month follow-ups, respectively. Baseline mobility but not muscle strength correlated with physical component summary (P = 0.01 and P = 0.23, respectively). Neither baseline mobility nor muscle strength correlated with mental component summary. At 12 months, muscle strength and mobility had significantly deteriorated (mean ankle dorsiflexion strength 11.0 lb (SD 1.5) from 14.0 lb (SD 2.2), P < 0.01; short physical performance battery 8.5 (SD 2.8) from 9.3 (SD 2.6), P < 0.01). Falls at 12 and 36 months were predicted by baseline mobility (P = 0.06 and P = 0.02, respectively) but not muscle strength. CONCLUSION: Physical parameters appear to be associated with meaningful patient outcomes and showed measurable deterioration over relatively short time frames. Interventions, with the potential to slow physical decline in people receiving maintenance dialysis, such as exercise programmes, warrant further investigation. PMID- 26890470 TI - Local Transmission of Zika Virus--Puerto Rico, November 23, 2015-January 28, 2016. AB - Zika virus, a mosquito-borne flavivirus, spread to the Region of the Americas (Americas) in mid-2015, and appears to be related to congenital microcephaly and Guillain-Barre syndrome (1,2). On February 1, 2016, the World Health Organization (WHO) declared the occurrence of microcephaly cases in association with Zika virus infection to be a Public Health Emergency of International Concern.* On December 31, 2015, Puerto Rico Department of Health (PRDH) reported the first locally acquired (index) case of Zika virus disease in a jurisdiction of the United States in a patient from southeastern Puerto Rico. During November 23, 2015-January 28, 2016, passive and enhanced surveillance for Zika virus disease identified 30 laboratory-confirmed cases. Most (93%) patients resided in eastern Puerto Rico or the San Juan metropolitan area. The most frequently reported signs and symptoms were rash (77%), myalgia (77%), arthralgia (73%), and fever (73%). Three (10%) patients were hospitalized. One case occurred in a patient hospitalized for Guillain-Barre syndrome, and one occurred in a pregnant woman. Because the most common mosquito vector of Zika virus, Aedes aegypti, is present throughout Puerto Rico, Zika virus is expected to continue to spread across the island. The public health response in Puerto Rico is being coordinated by PRDH with assistance from CDC. Clinicians in Puerto Rico should report all cases of microcephaly, Guillain-Barre syndrome, and suspected Zika virus disease to PRDH. Other adverse reproductive outcomes, including fetal demise associated with Zika virus infection, should be reported to PRDH. To avoid infection with Zika virus, residents of and visitors to Puerto Rico, particularly pregnant women, should strictly follow steps to avoid mosquito bites, including wearing pants and long sleeved shirts, using permethrin-treated clothing and gear, using an Environmental Protection Agency (EPA)-registered insect repellent, and ensuring that windows and doors have intact screens. PMID- 26890466 TI - A therapeutic nanoparticle vaccine against Trypanosoma cruzi in a BALB/c mouse model of Chagas disease. AB - Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1 biased immune response, as demonstrated by a significant increase in antigen specific IFNgamma-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system. PMID- 26890469 TI - A Poly(cobaloxime)/Carbon Nanotube Electrode: Freestanding Buckypaper with Polymer-Enhanced H2-Evolution Performance. AB - A freestanding H2-evolution electrode consisting of a copolymer-embedded cobaloxime integrated into a multiwall carbon nanotube matrix by pi-pi interactions is reported. This electrode is straightforward to assemble and displays high activity towards hydrogen evolution in near-neutral pH solution under inert and aerobic conditions, with a cobalt-based turnover number (TON(Co)) of up to 420. An analogous electrode with a monomeric cobaloxime showed less activity with a TON(Co) of only 80. These results suggest that, in addition to the high surface area of the porous network of the buckypaper, the polymeric scaffold provides a stabilizing environment to the catalyst, leading to further enhancement in catalytic performance. We have therefore established that the use of a multifunctional copolymeric architecture is a viable strategy to enhance the performance of molecular electrocatalysts. PMID- 26890471 TI - Incidence and causes of maternal mortality in the USA. AB - AIM: To characterize the most common causes and risk factors of maternal mortality in the USA and observe trends over the past 9 years. METHODS: We carried out a population-based retrospective cohort study using data from the Health Care Cost and Utilization Project, Nationwide Inpatient Sample. Women who were pregnant between 2003 and 2011 were identified. Baseline characteristics of pregnant women who died and those who lived were measured. ICD-9 codes for each cause of death were examined by up to three independent reviewers. Causes of death were categorized into the nine most common subgroups and trends were examined by tertiles of the period 2003-2011. RESULTS: During this 9-year period, there were approximately 7 million births and 1102 maternal deaths, for an overall incidence of 14.2 per 100 000 births. Primary causes of maternal death included sepsis (20.6%), cardiac disease (17.8%), hemorrhage (16.2%), venous thromboembolism (15.2%), and hypertensive disorders (9.4%). During the study period, there was a significant decrease in the frequency of sepsis from 33.2% to 10.0% and a non-significant decrease in venous thromboembolism from 19.1% to 12.9%. There were increases noted in all other groups, notably in terms of hemorrhage from 8.2% to 22.0% and hypertensive disorders from 2.1% to 16.4%. CONCLUSION: Maternal mortality remains a rare event. Although sepsis was the overall predominant cause of mortality during the study period, frequency declined over time and it was surpassed by hemorrhage and hypertensive disorders as the leading causes of maternal mortality. PMID- 26890473 TI - Endarterectomy, Stenting, or Neither for Asymptomatic Carotid-Artery Stenosis. PMID- 26890474 TI - Drain placement can safely be omitted for open partial nephrectomy: Results from a prospective randomized trial. AB - OBJECTIVES: To examine the benefit of drain placement during open partial nephrectomy. METHODS: Overall, 106 patients treated with open partial nephrectomy were enrolled in a prospective randomized trial. Based on the randomization, a drain was placed or omitted. Complications were assessed according to the Clavien classification. Pain level and requirement for analgesics was evaluated according to a customized pattern. RESULTS: There was no significant difference in the two groups regarding age, body mass index, American Society of Anesthesiologists score, tumor size and nephrometry (preoperative aspects and dimensions used for an anatomical classification). In terms of overall and drain-related complications, no advantage of placing a drain could be proven (P = 0.249). Patients with a drain suffered from a significantly higher pain level (P = 0.01) and showed prolonged mobilization (P < 0.001). There was no difference in bowel movements and requirement of additional analgesics (P = 0.347 and 0.11). CONCLUSIONS: The results of the study suggest that drain placement during open partial nephrectomy can safely be omitted, even in cases with violation of the collecting system. PMID- 26890475 TI - Effect of Embelin Against Lipopolysaccharide-induced Sickness Behaviour in Mice. AB - Sickness behaviour is a coordinated set of adaptive behavioural changes that develop in ill individuals during the course of an infection. It is relevant to understanding depression and some aspects of the suffering that in cancer. Embelin has been reported to possess antiinflammatory, neuroprotective and anxiolytic assets and has been shown to inhibit nuclear factor kappaB pathway and cytokine production. The present study was undertaken to investigate the effect of embelin isolated from Embelia ribes Burm in lipopolysaccharide (LPS)-induced sickness behaviour in mice. Adult male Swiss albino mice were pre-treated with embelin (10 and 20 mg/kg, p.o.) or dexamethasone (1 mg/kg, i.p.) for 3 days and then challenged with LPS (400 ug/kg, i.p.). At different time intervals of post LPS challenge, sickness behaviour was evaluated in the animals by battery of behavioural tests (plus maze, open field, light-dark box, forced swim, social behaviour assessment, sucrose preference and food and water intake). Levels of oxidative stress makers (reduced glutathione and lipid peroxidation) in mice brain were also analysed. LPS induced behavioural alterations, anhedonia and anorexia, in mice. Pre-treatment with embelin attenuated behavioural changes induced by LPS. In addition, embelin prevented anhedonia, anorexia and ameliorated brain oxidative stress markers. The experimental outcomes of the present study demonstrated protective effect of embelin in LPS-induced sickness behaviour in mice. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890476 TI - Natural product modulators of transient receptor potential (TRP) channels as potential anti-cancer agents. AB - Treatment of cancer is a significant challenge in clinical medicine, and its research is a top priority in chemical biology and drug discovery. Consequently, there is an urgent need for identifying innovative chemotypes capable of modulating unexploited drug targets. The transient receptor potential (TRPs) channels persist scarcely explored as targets, despite intervening in a plethora of pathophysiological events in numerous diseases, including cancer. Both agonists and antagonists have proven capable of evoking phenotype changes leading to either cell death or reduced cell migration. Among these, natural products entail biologically pre-validated and privileged architectures for TRP recognition. Furthermore, several natural products have significantly contributed to our current knowledge on TRP biology. In this Tutorial Review we focus on selected natural products, e.g. capsaicinoids, cannabinoids and terpenes, by highlighting challenges and opportunities in their use as starting points for designing natural product-inspired TRP channel modulators. Importantly, the de orphanization of natural products as TRP channel ligands may leverage their exploration as viable strategy for developing anticancer therapies. Finally, we foresee that TRP channels may be explored for the selective pharmacodelivery of cytotoxic payloads to diseased tissues, providing an innovative platform in chemical biology and molecular medicine. PMID- 26890472 TI - Long-Term Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis. AB - BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial, we found no significant difference between the stenting group and the endarterectomy group with respect to the primary composite end point of stroke, myocardial infarction, or death during the periprocedural period or any subsequent ipsilateral stroke during 4 years of follow-up. We now extend the results to 10 years. METHODS: Among patients with carotid-artery stenosis who had been randomly assigned to stenting or endarterectomy, we evaluated outcomes every 6 months for up to 10 years at 117 centers. In addition to assessing the primary composite end point, we assessed the primary end point for the long-term extension study, which was ipsilateral stroke after the periprocedural period. RESULTS: Among 2502 patients, there was no significant difference in the rate of the primary composite end point between the stenting group (11.8%; 95% confidence interval [CI], 9.1 to 14.8) and the endarterectomy group (9.9%; 95% CI, 7.9 to 12.2) over 10 years of follow-up (hazard ratio, 1.10; 95% CI, 0.83 to 1.44). With respect to the primary long-term end point, postprocedural ipsilateral stroke over the 10-year follow-up occurred in 6.9% (95% CI, 4.4 to 9.7) of the patients in the stenting group and in 5.6% (95% CI, 3.7 to 7.6) of those in the endarterectomy group; the rates did not differ significantly between the groups (hazard ratio, 0.99; 95% CI, 0.64 to 1.52). No significant between-group differences with respect to either end point were detected when symptomatic patients and asymptomatic patients were analyzed separately. CONCLUSIONS: Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups. (Funded by the National Institutes of Health and Abbott Vascular Solutions; CREST ClinicalTrials.gov number, NCT00004732.). PMID- 26890477 TI - Latent Tuberculosis Infection Test Agreement in the National Health and Nutrition Examination Survey. AB - RATIONALE: Latent tuberculosis infection (LTBI) test discordance is poorly understood. OBJECTIVES: To determine the frequency and predictors of tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube test (QFT) discordance in the U.S. METHODS: We analyzed data from a representative sample of the U.S. population ages 6 years and older who participated in the 2011-2012 National Health and Nutrition Examination Survey. We determined prevalence estimates of test positivity, calculated test agreement and kappa statistics, and performed multivariable logistic regression to determine predictors of discordance. MEASUREMENTS AND MAIN RESULTS: LTBI prevalence among the U.S. born ranged from 0.6% to 2.8%, depending on how LTBI was defined, with test agreement 97.0% and kappa 0.27 (95% confidence interval, 0.18-0.36). Prevalence among the foreign born ranged from 9.1% to 20.3%, depending on how LTBI was defined, with test agreement 81.6% and kappa 0.38 (95% confidence interval, 0.33-0.44). TST(+)/QFT( ) discordance was associated with age, male sex, black race, Mexican-American ethnicity, previous TB exposure, and past LTBI treatment in U.S.-born participants, but only with higher lymphocyte count in foreign-born participants. TST(-)/QFT(+) discordance was associated with older age, previous TB exposure, and past LTBI treatment in U.S.-born participants and with older age, male sex, and past LTBI treatment in foreign-born participants. CONCLUSIONS: In the largest population-based sample of concurrently performed TST and QFT tests in a low tuberculosis incidence population, prevalence estimates depended heavily on how LTBI was defined and test agreement was only fair. We identified several predictors of discordance warranting further study. PMID- 26890479 TI - Reduction-Responsive Sheddable Carbon Nanotubes Dispersed in Aqueous Solution. AB - A new approach to stabilize carbon nanotubes (CNTs) in aqueous solution with a reduction-responsive water-soluble polymer is reported. The novel polymer synthesized by a controlled radical polymerization is functionalized with pendant pyrene groups capable of adhering to the surface of CNTs through pi-pi noncovalent interactions, and labeled with disulfide linkages to exhibit reduction-responsive cleavage. Upon the cleavage of junction disulfide linkages in a reducing environment, water-soluble polymers are shed, retaining clean CNT surfaces for electrochemical catalytic reactions. PMID- 26890478 TI - Dissociation of gemcitabine chemosensitization by CHK1 inhibition from cell cycle checkpoint abrogation and aberrant mitotic entry. AB - In order to determine the relative contribution of checkpoint abrogation and subsequent aberrant mitotic entry to gemcitabine chemosensitization by CHK1 inhibition, we established a model utilizing the CDK inhibitors roscovitine or purvalanol A to re-establish cell cycle arrest and prevent aberrant mitotic entry in pancreatic cancer cells treated with gemcitabine and the CHK inhibitor AZD7762. In this study, we report that the extent of aberrant mitotic entry, as determined by flow cytometry for the mitotic marker phospho-Histone H3 (Ser10), did not reflect the relative sensitivities of pancreatic cancer cell lines to gemcitabine chemosensitization by AZD7762. In addition, re-establishing gemcitabine-induced cell cycle arrest either pharmacologically, with roscovitine or purvalanol A, or genetically, with cyclin B1 siRNA, did not inhibit chemosensitization uniformly across the cell lines. Furthermore, we found that AZD7762 augmented high-intensity gammaH2AX signaling in gemcitabine-treated cells, suggesting the presence of replication stress when CHK1 is inhibited. Finally, the ability of roscovitine to prevent chemosensitization correlated with its ability to inhibit AZD7762-induced high-intensity gammaH2AX, but not aberrant pHH3, suggesting that the effects of AZD7762 on DNA replication or repair rather than aberrant mitotic entry determine gemcitabine chemosensitization in pancreatic cancer cells. PMID- 26890481 TI - Characterization of Polyketide Synthase Machinery from the pks Island Facilitates Isolation of a Candidate Precolibactin. AB - Colibactin is a human gut bacterial genotoxin of unknown structure that has been linked to colon cancer. The biosynthesis of this elusive metabolite is directed by the pks gene cluster, which encodes a hybrid nonribosomal peptide synthetase polyketide synthase (NRPS-PKS) assembly line that is hypothesized to use the unusual polyketide building block aminomalonate. This biosynthetic pathway is thought to initially produce an inactive intermediate (precolibactin) that is processed to the active toxin. Here, we report the first in vitro biochemical characterization of the PKS components of the pks enzymatic assembly line. We evaluate PKS extender unit utilization and show that ClbG, a freestanding acyltransferase (AT) from the pks gene cluster, recognizes aminomalonyl-acyl carrier protein (AM-ACP) and transfers this building block to multiple PKS modules, including a cis-AT PKS ClbI. We also use genetics to explore the in vivo role of ClbG in colibactin and precolibactin biosynthesis. Unexpectedly, production of previously identified pks-associated metabolites is dramatically increased in a DeltaclbP/DeltaclbG mutant strain, enabling the first structure elucidation of a bithiazole-containing candidate precolibactin. This work provides new insights into the unusual biosynthetic capabilities of the pks gene cluster, offers further support for the hypothesis that colibactin directly damages DNA, and suggests that additional, uncharacterized pks-derived metabolites containing aminomalonate play critical roles in genotoxicity. PMID- 26890480 TI - Poly(Limonene Thioether) Scaffold for Tissue Engineering. AB - A photocurable thiol-ene network polymer, poly(limonene thioether) (PLT32o), is synthesized, characterized, fabricated into tissue engineering scaffolds, and demonstrated in vitro and in vivo. Micromolded PLT32o grids exhibit compliant, elastomeric mechanical behavior similar to grids made of poly(glycerol sebacate) (PGS), an established biomaterial. Multilayered PL32o scaffolds with regular, geometrically defined pore architectures support heart cell seeding and culture in a manner similar to multilayered PGS scaffolds. Subcutaneous implantation of multilayered PLT32o scaffolds with cultured heart cells provides long-term 3D structural support and retains the exogenous cells, whereas PGS scaffolds lose both their structural integrity and the exogenous cells over 31 d in vivo. PLT32o membrane implants retain their dry mass, whereas PGS implants lose 70 percent of their dry mass by day 31. Macrophages are initially recruited to PLT32o and PGS membrane implants but are no longer present by day 31. Facile synthesis and processing in combination with the capability to support heart cells in vitro and in vivo suggest that PLT32o can offer advantages for tissue engineering applications where prolonged in vivo maintenance of 3D structural integrity and elastomeric mechanical behavior are required. PMID- 26890482 TI - High-throughput profiling of antibiotic resistance genes in drinking water treatment plants and distribution systems. AB - Antibiotic resistance genes (ARGs) are present in surface water and often cannot be completely eliminated by drinking water treatment plants (DWTPs). Improper elimination of the ARG-harboring microorganisms contaminates the water supply and would lead to animal and human disease. Therefore, it is of utmost importance to determine the most effective ways by which DWTPs can eliminate ARGs. Here, we tested water samples from two DWTPs and distribution systems and detected the presence of 285 ARGs, 8 transposases, and intI-1 by utilizing high-throughput qPCR. The prevalence of ARGs differed in the two DWTPs, one of which employed conventional water treatments while the other had advanced treatment processes. The relative abundance of ARGs increased significantly after the treatment with biological activated carbon (BAC), raising the number of detected ARGs from 76 to 150. Furthermore, the final chlorination step enhanced the relative abundance of ARGs in the finished water generated from both DWTPs. The total enrichment of ARGs varied from 6.4-to 109.2-fold in tap water compared to finished water, among which beta-lactam resistance genes displayed the highest enrichment. Six transposase genes were detected in tap water samples, with the transposase gene TnpA-04 showing the greatest enrichment (up to 124.9-fold). We observed significant positive correlations between ARGs and mobile genetic elements (MGEs) during the distribution systems, indicating that transposases and intI-1 may contribute to antibiotic resistance in drinking water. To our knowledge, this is the first study to investigate the diversity and abundance of ARGs in drinking water treatment systems utilizing high-throughput qPCR techniques in China. PMID- 26890483 TI - Are intertidal soft sediment assemblages affected by repeated oil spill events? A field-based experimental approach. AB - This study investigates the impact of repeated diesel spills on the structure of intertidal macrofaunal assemblages of a subtropical estuary. Three frequencies of exposure events were compared against two dosages of oil in a factorial experiment with asymmetrical controls. Hypotheses were tested to distinguish between (i) the overall effect of oil spills, (ii) the effect of diesel dosage via different exposure regimes, and (iii) the effect of time since last spill. Repeated oil spills dramatically altered the overall structure of assemblages and reduced the total density of macrofauna and densities of dominant taxa. Increasing the frequency of oil spills negatively affected macrofauna. In general, frequent low-dosage oil spills were more deleterious than infrequent high-dosage ones. However, increases in densities of some taxa, mainly the gastropod Heleobia australis, were observed in response to infrequent spills. Our results highlight the importance of repeated exposure events in determining the extent of oil impacts. PMID- 26890484 TI - Effects of diuron and carbofuran pesticides in their pure and commercial forms on Paramecium caudatum: The use of protozoan in ecotoxicology. AB - Toxic effects of diuron and carbofuran on Paramecium caudatum were evaluated. Acute and chronic tests were conducted with diuron and carbofuran active ingredients and their commercial formulations, Diuron Nortox((r)) 500 SC and Furadan((r)) 350 SC, respectively. The sensitivity range of P. caudatum to reference substance sodium chloride was established. A preliminary risk assessment of diuron and carbofuran for Brazilian water bodies was performed. The tests indicated that toxicity of pure diuron and its commercial formulation was similar, while the commercial product carbofuran was more toxic than its pure form. In acute tests, readings were carried out at 2, 3, 4 and 6 h and showed an increase of mortality with increasing exposure time. The sensitivity of P. caudatum to NaCl ranged from 3.31 to 4.44 g L(-1), averaging 3.88 g L(-1). For diuron, the 6 h LC50 was 64.6 +/- 3.3 mg L(-1) for its pure form and 62.4 +/- 2.5 mg L(-1) for its commercial formulation. Carbofuran active ingredient was less toxic than that of diuron, presenting a 6 h LC50 of 142.0 +/- 2.4 mg L(-1) for its pure form and 70.4 +/- 2.2 mg L(-1) for its commercial product. Chronic tests showed that these pesticides cause significant decrease on population growth, generation number and biomass of P. caudatum. The 24 h IC50 was 7.10 +/- 0.58 mg L(-1) for pure diuron, 6.78 +/- 0.92 mg L(-1) for commercial diuron, 22.95 +/- 3.57 mg L(-1) for pure carbofuran and 4.98 +/- 0.62 mg L(-1) for commercial carbofuran. Preliminary risk assessment indicated that diuron and carbofuran present potential ecological risks for Brazilian water bodies. P. caudatum was a suitable and sensitive test organism to evaluate diuron and carbofuran toxicity to freshwater protozooplankton and, taking into account the relevant role of protozoans in aquatic environments, we strongly recommend its inclusion in ecotoxicological studies. PMID- 26890485 TI - Quantifying Transmission Investment in Malaria Parasites. AB - Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment. PMID- 26890486 TI - Comparison of contrast-enhanced ultrasonography with virtual touch tissue quantification in the evaluation of focal liver lesions. AB - PURPOSE: To evaluate the diagnostic efficacy of virtual touch tissue quantification (VTQ) and contrast-enhanced ultrasonography (CEUS), separately and in combination, in diagnosing malignant focal liver lesions (FLLs). METHODS: Forty-six patients with 55 FLLs (28 benign and 27 malignant) underwent both VTQ and CEUS. The diagnostic values of VTQ and CEUS, alone and in combination, were compared. RESULTS: The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of CEUS were 92.6% (25/27), 96.4% (27/28), 94.5% (52/55), 96.2% (25/26), and 93.1% (27/29), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ with a cutoff of 2.22 m/s were 51.9% (14/27), 85.7% (24/28), 69.1% (38/55), 77.8% (14/18), and 64.9% (24/37), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ and CEUS combined were 96.3% (26/27), 82.1% (23/28), 89.1% (49/55), 83.9% (26/31), and 95.8% (23/24), respectively. Comparing the accuracies of the three methods, the diagnostic values of CEUS and of the combination of CEUS with VTQ were significantly higher than those of VTQ alone (p <= 0.01). There was no significant difference between the combination of CEUS with VTQ and CEUS (p = 0.49). CONCLUSIONS: CEUS is superior to VTQ in diagnosing malignant FLLs. Adding VTQ to CEUS did not improve the diagnosis of FLLs. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:347-353, 2016. PMID- 26890488 TI - Under the Influence: The Interplay among Industry, Publishing, and Drug Regulation. AB - The relationships among academe, publishing, and industry can facilitate commercial bias in how drug efficacy and safety data are obtained, interpreted, and presented to regulatory bodies and prescribers. Through a critique of published and unpublished trials submitted to the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for approval of a new antidepressant, vortioxetine, we present a case study of the "ghost management" of the information delivery process. We argue that currently accepted practices undermine regulatory safeguards aimed at protecting the public from unsafe or ineffective medicines. The economies of influence that may intentionally and unintentionally produce evidence-biased-rather than evidence-based-medicine are identified. This is not a simple story of author financial conflicts of interest, but rather a complex tale of ghost management of the entire process of bringing a drug to market. This case study shows how weak regulatory policies allow for design choices and reporting strategies that can make marginal products look novel, more effective, and safer than they are, and how the selective and imbalanced reporting of clinical trial data in medical journals results in the marketing of expensive "me-too" drugs with questionable risk/benefit profiles. We offer solutions for neutralizing these economies of influence. PMID- 26890487 TI - Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review. AB - BACKGROUND: Neglected Tropical Diseases (NTDs) not only cause health and life expectancy loss, but can also lead to economic consequences including reduced ability to work. This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five worldwide most prevalent NTDs: lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (ascariasis, trichuriasis, and hookworm infection) and trachoma. These diseases are eligible to preventive chemotherapy (PCT). METHODOLOGY/PRINCIPAL FINDINGS: Eleven bibliographic databases were searched using different names of all NTDs and various keywords relating to productivity. Additional references were identified through reference lists from relevant papers. Of the 5316 unique publications found in the database searches, thirteen papers were identified for lymphatic filariasis, ten for onchocerciasis, eleven for schistosomiasis, six for soil-transmitted helminths and three for trachoma. Besides the scarcity in publications reporting the degree of productivity loss, this review revealed large variation in the estimated productivity loss related to these NTDs. CONCLUSIONS: It is clear that productivity is affected by NTDs, although the actual impact depends on the type and severity of the NTD as well as on the context where the disease occurs. The largest impact on productivity loss of individuals affected by one of these diseases seems to be due to blindness from onchocerciasis and severe schistosomiasis manifestations; productivity loss due to trachoma-related blindness has never been studied directly. However, productivity loss at an individual level might differ from productivity loss at a population level because of differences in the prevalence of NTDs. Variation in estimated productivity loss between and within diseases is caused by differences in research methods and setting. Publications should provide enough information to enable readers to assess the quality and relevance of the study for their purposes. PMID- 26890489 TI - Complete genome analysis of hepatitis B virus in human immunodeficiency virus infected and uninfected South Africans. AB - Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are highly endemic in South Africa. Data on the complete genome sequences of HBV in HIV-positive patients in South Africa are scanty. This study characterized the complete HBV genome isolated from both HIV-positive and negative patients at the Dr George Mukhari Academic Hospital (DGMAH), Pretoria. Serum samples from nine (five HIV-positive and four HIV-negative) patients attending the DGMAH from 2007 to 2011 were serologically tested, amplified, and sequenced for complete genome. Phylogenetic tree was constructed using MEGA6.0. Mutations were analyzed by comparing the sequences with genotype-matched GenBank references. Eight patients were HBsAg positive, with only one from the HIV positive group being negative. Phylogenetic analysis of the complete genome sequences classified them into five genotypes; A1 (n = 4), A2 (n = 1), C1 (n = 2), D1 (n = 1), and D3 (n = 1). Deletions up to 35 nucleotides in length were identified in this study. No drug resistance mutations were identified in the P ORF, while the L217R mutation was identified in one subgenotype A2 sequence. The double (A1762T/G1764A) and triple (T1753C/A1762T/G1764A) mutations in the Basal core promoter were identified in four and two sequences, respectively. In the core region, mutation G1888A was identified in four of the subgenotype A1 sequences. In conclusion, this study has added to the limited South African data on HBV genotypes and mutations in HBV/HIV co-infected and HBV mono-infected patients, based on complete HBV genome analysis. Subgenotype A1 was predominant, and no drug-resistant mutants were detected in the study. J. Med. Virol. 88:1560-1566, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890491 TI - Co-designing technologies in the context of hypertension care: Negotiating participation and technology use in design meetings. AB - : Research Interest: In this article, we take an interest in the new kind of relation that has been claimed to be urgently required between health services and patients. Co-production of health services implies fundamental changes in the ways medical care is organized and delivered. Usually, technologies are put forth as potential solutions to problems that might occur when establishing such new relations. AIMS: The aim of this study is to scrutinize how different perspectives were brought into the discussions as the concrete design and use of a mobile phone application were introduced, and how participants anticipated and negotiated their own participation in the design project. METHODS: This article reports results from an explorative study of a co-design project in hypertension care wherein health professionals and patients were invited to co-design some features of the application they were later to use. RESULTS/CONCLUSIONS: The study shows that new practices of self-treatment are not likely to take place without the cooperation of patients, since they are to provide the observational data necessary for the professionals' work. The negotiations are needed to balance patients' concerns of being monitored by technology and their needs of being in control of their everyday lives and activities. PMID- 26890490 TI - Daily rhythmicity of high affinity copper transport. AB - A differential demand for copper (Cu) of essential cupro-proteins that act within the mitochondrial and chloroplastal electronic transport chains occurs along the daily light/dark cycles. This requires a fine-tuned spatiotemporal regulation of Cu delivery, becoming especially relevant under non-optimal growth conditions. When scarce, Cu is imported through plasma membrane-bound high affinity Cu transporters (COPTs) whose coding genes are transcriptionally induced by the SPL7 transcription factor. Temporal homeostatic mechanisms are evidenced by the presence of multiple light- and clock-responsive regulatory cis elements in the promoters of both SPL7 and its COPT targets. A model is presented here for such temporal regulation that is based on the synchrony between the basal oscillatory pattern of SPL7 and its targets, such as COPT2. Conversely, Cu feeds back to coordinate intracellular Cu availability on the SPL7-dependent regulation of further Cu acquisition. This occurs via regulation at COPT transporters. Moreover, exogenous Cu affects several circadian-clock components, such as the timing of GIGANTEA transcript abundance. Together we propose that there is a dynamic response to Cu that is integrated over diurnal time to maximize metabolic efficiency under challenging conditions. PMID- 26890492 TI - Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation. AB - Bone continuously undergoes remodeling by a tightly regulated process that involves osteoblast differentiation from Mesenchymal Stem Cells (MSC). However, commitment of MSC to osteoblastic lineage is a poorly understood process. Chromatin organization functions as a molecular gatekeeper of DNA functions. Detection of sites that are hypersensitive to Dnase I has been used for detailed examination of changes in response to hormones and differentiation cues. To investigate the early steps in commitment of MSC to osteoblasts, we used a model human temperature-sensitive cell line, hFOB. When shifted to non-permissive temperature, these cells undergo "spontaneous" differentiation that takes several weeks, a process that is greatly accelerated by osteogenic induction media. We performed Dnase I hypersensitivity assays combined with deep sequencing to identify genome-wide potential regulatory events in cells undergoing early steps of commitment to osteoblasts. Massive reorganization of chromatin occurred within hours of differentiation. Whereas ~30% of unique DHS sites were located in the promoters, the majority was outside of the promoters, designated as enhancers. Many of them were at novel genomic sites and need to be confirmed experimentally. We developed a novel method for identification of cellular networks based solely on DHS enhancers signature correlated to gene expression. The analysis of enhancers that were unique to differentiating cells led to identification of bone developmental program encompassing 147 genes that directly or indirectly participate in osteogenesis. Identification of these pathways provided an unprecedented view of genomic regulation during early steps of differentiation and changes related to WNT, AP-1 and other pathways may have therapeutic implications. PMID- 26890493 TI - The Relationship between Mental and Somatic Practices and Wisdom. AB - In this study we sought to explore how experience with specific mental and somatic practices is associated with wisdom, using self-report measures of experience and wisdom. We administered standard surveys to measure wisdom and experience among four groups of practitioners of mental and somatic practices, namely, meditators, practitioners of the Alexander Technique, practitioners of the Feldenkrais Method, and classical ballet dancers. We additionally administered surveys of trait anxiety and empathy to all participants to explore possible mediating relationships of experience and wisdom by characteristics thought to be components of wisdom. Wisdom was higher on average among meditation practitioners, and lowest among ballet dancers, and this difference held when controlling for differences in age between practices, supporting the view that meditation is linked to wisdom and that ballet is not. However, we found that increased experience with meditation and ballet were both positively associated with wisdom, and that lowered trait anxiety mediated this positive association among meditation practitioners, and, non-significantly, among ballet dancers. These results suggest that not all practices that are purported to affect mental processing are related to wisdom to the same degree and different kinds of experience appear to relate to wisdom in different ways, suggesting different mechanisms that might underlie the development of wisdom with experience. PMID- 26890494 TI - Meeting report: Adaptation and communication of bacterial pathogens. AB - Bacteria usually live in complex environments, sharing niche and resources with other bacterial species, unicellular eukaryotic cells or complex organisms. Thus, they have evolved mechanisms to communicate, to compete and to adapt to changing environment as diverse as human tissues, animals or plants. Understanding the molecular mechanisms underlying these adaptation processes is therefore of primary importance for epidemiology and human health protection, and was the focus of a Current Trends in Biomedicine workshop organized by the International University of Andalucia in late October 2015 in Baeza (Spain). The topic was covered by complementary sessions: (i) interbacterial communication and competition that enable a better access to nutrients or a more efficient colonization of the ecological niche, (ii) adaptation of intracellular pathogens to their host, focusing on metabolic pathways, adaptive mechanisms and populational heterogeneity, and (iii) adaptation of animal and plant pathogens as well as plant-associated bacteria to a plant niche. This workshop emphasized the broad repertoire of mechanisms and factors bacteria have evolved to become efficient pathogens. PMID- 26890495 TI - Bortezomib-based triplets are associated with a high probability of dialysis independence and rapid renal recovery in newly diagnosed myeloma patients with severe renal failure or those requiring dialysis. AB - Renal failure (RF) is a common and severe complication of symptomatic myeloma, associated with significant morbidity and mortality. Such patients are commonly excluded from clinical trials. Bortezomib/dexamethasone (VD)-based regimens are the backbone of the treatment of newly diagnosed MM patients who present with severe RF even those requiring dialysis. We analyzed the outcomes of 83 consecutive bortezomib-treated patients with severe RF (eGFR < 30 ml/min/1.73 m(2) ), of which 31 (37%) required dialysis. By IMWG renal response criteria, 54 (65%) patients achieved at least MRrenal, including CRrenal in 35% and PRrenal in 12%. Triplet combinations (i.e., VD plus a third agent) versus VD alone were associated with higher rates of renal responses (72 vs. 50%; P = 0.06). Fifteen of the 31 (48%) patients became dialysis independent within a median of 217 days (range 11-724). Triplets were associated with a higher probability of dialysis discontinuation (57 vs. 35%). Serum free light chain (sFLC) level >=11,550 mg/L was associated with lower rates of major renal response, longer time to major renal response, lower probability, and longer time to dialysis discontinuation. Rapid myeloma response (>=PR within the first month) was also associated with higher rates of renal response. Patients who became dialysis-independent had longer survival than those remaining on dialysis. In conclusion, VD-based triplets are associated with a significant probability of renal response and dialysis discontinuation, improving the survival of patients who became dialysis independent. Rapid disease response is important for renal recovery and sFLCs are predictive of the probability and of the time required for renal response. PMID- 26890496 TI - Quantitative Magnetic Separation of Particles and Cells Using Gradient Magnetic Ratcheting. AB - Extraction of rare target cells from biosamples is enabling for life science research. Traditional rare cell separation techniques, such as magnetic activated cell sorting, are robust but perform coarse, qualitative separations based on surface antigen expression. A quantitative magnetic separation technology is reported using high-force magnetic ratcheting over arrays of magnetically soft micropillars with gradient spacing, and the system is used to separate and concentrate magnetic beads based on iron oxide content (IOC) and cells based on surface expression. The system consists of a microchip of permalloy micropillar arrays with increasing lateral pitch and a mechatronic device to generate a cycling magnetic field. Particles with higher IOC separate and equilibrate along the miropillar array at larger pitches. A semi-analytical model is developed that predicts behavior for particles and cells. Using the system, LNCaP cells are separated based on the bound quantity of 1 MUm anti-epithelial cell adhesion molecule (EpCAM) particles as a metric for expression. The ratcheting cytometry system is able to resolve a +/-13 bound particle differential, successfully distinguishing LNCaP from PC3 populations based on EpCAM expression, correlating with flow cytometry analysis. As a proof-of-concept, EpCAM-labeled cells from patient blood are isolated with 74% purity, demonstrating potential toward a quantitative magnetic separation instrument. PMID- 26890497 TI - Marginal mean models for zero-inflated count data. AB - Zero-inflated regression models have emerged as a popular tool within the parametric framework to characterize count data with excess zeros. Despite their increasing popularity, much of the literature on real applications of these models has centered around the latent class formulation where the mean response of the so-called at-risk or susceptible population and the susceptibility probability are both related to covariates. While this formulation in some instances provides an interesting representation of the data, it often fails to produce easily interpretable covariate effects on the overall mean response. In this article, we propose two approaches that circumvent this limitation. The first approach consists of estimating the effect of covariates on the overall mean from the assumed latent class models, while the second approach formulates a model that directly relates the overall mean to covariates. Our results are illustrated by extensive numerical simulations and an application to an oral health study on low income African-American children, where the overall mean model is used to evaluate the effect of sugar consumption on caries indices. PMID- 26890498 TI - Dual C-F, C-H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls. AB - Multifluorinated biaryls are challenging to synthesize and yet are an important class of molecules. Because of the difficulty associated with selective fluorination, this class of molecules represent a formidable synthetic challenge. An alternative approach to selective fluorination of biaryls is to couple an arene that already possesses C-F bonds in the desired location. This strategy has been regularly utilized and relies heavily on traditional cross-coupling strategies that employ organometallics and halides (or pseudohalides) in order to achieve the coupling. Herein we report conditions for the photocatalytic coupling via direct functionalization of the C-F bond of a perfluoroarene and C-H bond of the other arene to provide an expedient route to multifluorinated biaryls. The mild conditions and good functional group tolerance enable a broad scope, including access to the anti-Minisci product of basic heterocycles. Finally, we demonstrate the value of the C-F functionalization approach by utilizing the high fluorine content to systematically build complex biaryls containing between two and five Caryl-F bonds via the synergistic use of photocatalysis and SNAr chemistry. PMID- 26890500 TI - Negative outcomes of unbalanced opioid policy supported by clinicians, politicians, and the media. AB - Harmful and nonmedical use of prescription opioids has increased precipitously in the United States and some other countries in recent years, but not everywhere around the world. Addressing this problem requires attention to scientific data and to objective and balanced consideration of factors driving the problems. Unfortunately, the situation has been blurred by some politicians, health professionals, and the media by their using inadequate concepts, misrepresenting and exaggerating facts, and demonizing pain patients. In this article, we analyze what has occurred and present what we believe to be a balanced view of the problems. We advocate comprehensive drug control policies implemented in a way to reduce harmful use and diversion problems balancing the public health benefits and risks of opioid medications. We make recommendations for responsible prescribing, including implementing the World Health Organization (WHO) policy guidelines and similar United Nations Office of Drug Control (UNODC), which we believe can contribute measurably to the prevention of diversion of prescription opioids while ensuring patient access to the most appropriate medicines. Measures to reduce the risks of nonmedical use of opioid medicines should be based to the greatest extent possible on accurate evaluation of the mechanisms leading to such use, including diversion activities. PMID- 26890501 TI - Mycobacterium arupense as an Emerging Cause of Tenosynovitis. PMID- 26890502 TI - Getting and Staying Active. PMID- 26890503 TI - PHYSIOLOGICAL EFFECTS OF RESVERATROL AND COUMARIC ACID ON TWO MAJOR GROUNDNUT PESTS AND THEIR EGG PARASITOID BEHAVIOR. AB - Groundnut, Arachis hypogea L., is one of the plant species that synthesizes phenolic compounds, resveratrol and coumaric acid. They are induced as a defense strategy in plant in response to feeding lepidopterans. The present study investigated the role of resveratrol and coumaric acid in producing antiherbivore effects as a direct defense against two major groundnut pests, Spodoptera litura F. and Amsacta albistriga W., and in indirect defense by attracting the egg parasitoid Trichogramma chilonis Ishii under laboratory conditions. The phenolic compounds deterred the feeding of both pests and caused reduction in the larval weights in a dose-dependent manner in leaf disk bioassays. Antioxidant mechanisms of larvae fed with these phenols were measured by estimating the activities of superoxide dismutase (SOD), ascorbate peroxidase (APOX), and catalase (CAT). Enzyme activities increased significantly in experimental larvae, more so in resveratrol-treated than in coumaric acid treated larvae. Feeding larvae with resveratrol and coumaric acid resulted in enhanced activities of detoxifying enzymes, carboxyl esterase (EST), and glutathione-S-transferase (GST) in the midgut tissues of both species, indicating the toxic nature of these compounds. Trichogramma chilonis was more attracted toward coumaric acid treatments in Y olfactometer tests than to resveratrol. This study contributes to the understanding of the roles of resveratrol and coumaric acid in direct as well as indirect defense, we infer a possible utilization of these compounds in alternate measures of groundnut pest control in future. PMID- 26890505 TI - Local Free-Style Perforator Flaps in Head and Neck Reconstruction: An Update and a Useful Classification. AB - BACKGROUND: Any standard skin flap of the body including a detectable or identified perforator at its axis can be safely designed and harvested in a free style fashion. METHODS: Fifty-six local free-style perforator flaps in the head and neck region, 33 primary and 23 recycle flaps, were performed in 53 patients. The authors introduced the term "recycle" to describe a perforator flap harvested within the borders of a previously transferred flap. A Doppler device was routinely used preoperatively for locating perforators in the area adjacent to a given defect. The final flap design and degree of mobilization were decided intraoperatively, depending on the location of the most suitable perforator and the ability to achieve primary closure of the donor site. Based on clinical experience, the authors suggest a useful classification of local free-style perforator flaps. RESULTS: All primary and 20 of 23 recycle free-style perforator flaps survived completely, providing tension-free coverage and a pleasing final contour for patients. In the remaining three recycle cases, the skeletonization of the pedicle resulted in pedicle damage, because of surrounding postradiotherapy scarring and flap failure. All donor sites except one were closed primarily, and all of them healed without any complications. CONCLUSIONS: The free-style concept has significantly increased the potential and versatility of the standard local and recycled head and neck flap alternatives for moderate to large defects, providing a more robust, custom-made, tissue-sparing, and cosmetically superior outcome in a one-stage procedure, with minimal donor-site morbidity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID- 26890506 TI - Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma. AB - BACKGROUND: A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. METHODS: Twenty-six breast implant-associated ALCL samples were analyzed for the presence of biofilm by real time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. RESULTS: Both the breast implant-associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant-associated ALCL, 4.7 * 10 cells/mg of tissue; capsule, 4.9 * 10 cells/mg of tissue). Analysis of the microbiome in breast implant-associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p < 0.05). In contrast, significantly more Staphylococcus spp. were found associated with nontumor capsule specimens compared with breast implant-associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. CONCLUSIONS: This novel finding of bacterial biofilm and a distinct microbiome in breast implant-associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, V. PMID- 26890507 TI - A Comparison of the Full and Short-Scar Face-Lift Incision Techniques in Multiple Sets of Identical Twins. AB - BACKGROUND: Choosing the ideal face-lift technique for a patient presents an added challenge for the plastic surgeon. With the multitude of well-established variations of this procedure, it would be beneficial to define which facioplasty technique produces the optimal result. By comparing the postoperative results from two of the most popularized face-lift incision techniques in monozygotic twins, it is hypothesized that the "best" technique may be determined. METHODS: Four sets of identical twins and one set of identical triplets underwent face lift surgery performed by the senior author (D.E.A.). Incision technique selection was randomized, with the first-born twin undergoing the full-incision operation. Short- and long-term postoperative photographs were taken at approximately 1 and 5 years and subsequently graded by eight board-certified plastic surgeons with over 100 years of combined experience. RESULTS: Data obtained from this study suggest that no difference between these incisions exists at the shorter term follow-up. However, analysis of the long-term follow up revealed a significant difference between the average scores assigned to the neck region, with the full-incision technique receiving a higher score. CONCLUSIONS: These findings suggest that at the short-term follow-up, both the short-scar and full-incision techniques yield comparable results. However, at the longer term follow-up, a significant difference appears between the two procedures exclusively in the neck region. Although a shorter incision is appealing to the patient and surgeon, this study suggests that the full incision may offer a superior long-term result in the neck. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. PMID- 26890508 TI - Which Factors Are Associated with Open Reduction of Adult Mandibular Condylar Injuries? AB - BACKGROUND: The purpose of this study was to identify factors associated with the decision to perform open reduction and internal fixation of mandibular condylar fractures. METHODS: This was a retrospective cohort study of patients with mandibular condylar fractures managed by the plastic and reconstructive surgery, oral and maxillofacial surgery, and otorhinolaryngology services over a 15-year period. Bivariate associations and a multiple logistic regression model were computed for injury characteristics that were associated with open reduction and internal fixation. For all analyses, a value of p <= 0.05 was considered significant. RESULTS: Six hundred fifty-four condylar injuries were identified in 547 patients. The sample's mean age was 36.0 +/- 16.5 years, 20.5 percent were women, and 63 percent were Caucasian. The most common mechanisms of injury were motor vehicle collisions (49 percent), 53.4 percent involved the subcondylar region and 20 percent were bilateral injuries. Associated noncondylar mandibular fractures were present in 60 percent of cases; 20.7 percent were managed with open reduction and internal fixation. The overall complication rate was 21.6 percent. In a multiple logistic regression model, factors associated with an increased likelihood of open reduction and internal fixation were the presence of extracondylar mandibular injuries, condylar neck or subcondylar region injuries, increasing dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery (p <= 0.04). CONCLUSIONS: Increasing severity of mandibular injury, lower level of fracture, joint dislocation, and treatment by plastic and reconstructive surgery/oral and maxillofacial surgery are associated with open reduction and internal fixation of mandibular condylar injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III. PMID- 26890509 TI - Midcarpal and Scaphotrapeziotrapezoid Arthritis in Patients with Carpometacarpal Arthritis. AB - BACKGROUND: Carpometacarpal arthroplasty provides well-documented pain relief with preservation of thenar function in basal joint arthritis treatment. Nevertheless, some patients continue to have pain following surgery. The authors hypothesize that unrecognized midcarpal (capitolunate) arthritis is a contributor to persistent pain after carpometacarpal arthroplasty. The prevalence of midcarpal arthritis in patients with basal joint arthritis is unknown. This article establishes the radiographic prevalence of midcarpal arthritis in patients with carpometacarpal arthritis. METHODS: Patients with basal joint arthritis were identified from a search using International Classification of Diseases, Ninth Revision code 716.94. Hand radiographs were reviewed and graded using the Eaton classification and Sodha classification for carpometacarpal arthritis. Scaphotrapeziotrapezoid arthritis and midcarpal arthritis were graded using the Sodha classification for arthritis as follows: grade 1, no or nearly no arthrosis; grade 2, definite arthrosis but not severe; and grade 3, severe arthrosis. RESULTS: Eight hundred ninety-six radiographs were reviewed. The prevalence of scaphotrapeziotrapezoid arthritis in this population was 64 percent. The prevalence of midcarpal arthritis in this population was 23.5 percent. The prevalence of midcarpal arthritis in patients with radiologic evidence of carpometacarpal arthritis was 25.4 percent. The prevalence of severe midcarpal arthritis was 7 percent. CONCLUSIONS: The prevalence of midcarpal arthritis in patients with basal joint arthritis is 24 percent. The presence of two locations of arthritis may explain persistent hand and wrist pain in this population despite carpometacarpal arthroplasty. Clinically, these data will allow hand surgeons to better educate patients with basal joint arthritis regarding the possibility of incomplete pain relief following carpometacarpal arthroplasty. PMID- 26890510 TI - Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury. AB - BACKGROUND: Therapies to improve outcomes following peripheral nerve injury are lacking. Prolonged denervation of muscle and Schwann cells contributes to poor outcomes. In this study, the authors assess the effects of growth hormone therapy on axonal regeneration, Schwann cell and muscle maintenance, and end-organ reinnervation in rats. METHODS: Male Sprague-Dawley rats underwent sciatic nerve transection and repair and femoral nerve transection without repair and received either daily subcutaneous growth hormone (0.4 mg/day) or no treatment (n = 8 per group). At 5 weeks, the authors assessed axonal regeneration within the sciatic nerve, muscle atrophy within the gastrocnemius muscle, motor endplate reinnervation within the soleus muscle, and Schwann cell proliferation within the denervated distal femoral nerve. RESULTS: Growth hormone-treated animals demonstrated greater percentage increase in body mass (12.2 +/- 1.8 versus 8.5 +/ 1.5; p = 0.0044), greater number of regenerating myelinated axons (13,876 +/- 2036 versus 8645 +/- 3279; p = 0.0018) and g-ratio (0.64 +/- 0.11 versus 0.51 +/- 0.06; p = 0.01), greater percentage reinnervation of motor endplates (75.8 +/- 8.7 versus 38.2 +/- 22.6; p = 0.0008), and greater muscle myofibril cross sectional area (731.8 +/- 157 MUm versus 545.2 +/- 144.3 MUm; p = 0.027). CONCLUSIONS: In male rats, growth hormone therapy accelerates axonal regeneration, reduces muscle atrophy, and promotes muscle reinnervation. Growth hormone therapy may also maintain proliferating Schwann cells in the setting of prolonged denervation. These findings suggest potential for improved outcomes with growth hormone therapy after peripheral nerve injuries. PMID- 26890511 TI - A New Technique to Improve Velopharyngeal Dysfunction by Combining the Radical Intravelar Veloplasty and Overlapping Intravelar Veloplasty for Primary Palatoplasty. PMID- 26890512 TI - Fibrous Dysplasia: Management of the Optic Canal. PMID- 26890513 TI - Abdominoplasty: Risk Factors, Complication Rates, and Safety of Combined Procedures. PMID- 26890514 TI - Labia Minora Reduction: A Growing Female Need. PMID- 26890515 TI - Dynamics of Gluteal Cleft Morphology in Lower Body Lift: Predictors of Unfavorable Outcomes. PMID- 26890516 TI - Reply: Progressive Tightening of the Levator Veli Palatini Muscle Improves Velopharyngeal Dysfunction in Early Outcomes of Primary Palatoplasty. PMID- 26890517 TI - Reply: Dynamics of Gluteal Cleft Morphology in Lower Body Lift: Predictors of Unfavorable Outcomes. PMID- 26890518 TI - Reply: Growing Body of Evidence Supports Safety of Female Genital Cosmetic Surgery. PMID- 26890519 TI - Comparison of Outcomes for Normal Saline and an Antiseptic Solution for Negative Pressure Wound Therapy with Instillation. PMID- 26890521 TI - Reply: Fibrous Dysplasia: Management of the Optic Canal. PMID- 26890520 TI - Reply: Abdominoplasty: Risk Factors, Complication Rates, and Safety of Combined Procedures. PMID- 26890522 TI - Activity capacity and activity performance: time to be specific? PMID- 26890524 TI - Utilizing stem cells for three-dimensional neural tissue engineering. AB - Three-dimensional neural tissue engineering has made great strides in developing neural disease models and replacement tissues for patients. However, the need for biomimetic tissue models and effective patient therapies remains unmet. The recent push to expand 2D neural tissue engineering into the third dimension shows great potential to advance the field. Another area which has much to offer to neural tissue engineering is stem cell research. Stem cells are well known for their self-renewal and differentiation potential and have been shown to give rise to tissues with structural and functional properties mimicking natural organs. Application of these capabilities to 3D neural tissue engineering may be highly useful for basic research on neural tissue structure and function, engineering disease models, designing tissues for drug development, and generating replacement tissues with a patient's genetic makeup. Here, we discuss the vast potential, as well as the current challenges, unique to integration of 3D fabrication strategies and stem cells into neural tissue engineering. We also present some of the most significant recent achievements, including nerve guidance conduits to facilitate better healing of nerve injuries, functional 3D biomimetic neural tissue models, physiologically relevant disease models for research purposes, and rapid and effective screening of potential drugs. PMID- 26890523 TI - Universal Molecular Scaffold for Facile Construction of Multivalent and Multimodal Imaging Probes. AB - Multivalent and multimodal imaging probes are rapidly emerging as powerful chemical tools for visualizing various biochemical processes. Herein, we described a bifunctional chelator (BFC)-based scaffold that can be used to construct such promising probes concisely. Compared to other reported similar scaffolds, this new BFC scaffold demonstrated two major advantages: (1) significantly simplified synthesis due to the use of this new BFC that can serve as chelator and linker simultaneously; (2) highly efficient synthesis rendered by using either click chemistry and/or total solid-phase synthesis. In addition, the versatile utility of this molecular scaffold has been demonstrated by constructing several multivalent/multimodal imaging probes labeled with various radioisotopes, and the resulting radiotracers demonstrated substantially improved in vivo performance compared to the two individual monomeric counterparts. PMID- 26890525 TI - Full Genome Sequence-Based Comparative Study of Wild-Type and Vaccine Strains of Infectious Laryngotracheitis Virus from Italy. AB - Infectious laryngotracheitis (ILT) is an acute and highly contagious respiratory disease of chickens caused by an alphaherpesvirus, infectious laryngotracheitis virus (ILTV). Recently, full genome sequences of wild-type and vaccine strains have been determined worldwide, but none was from Europe. The aim of this study was to determine and analyse the complete genome sequences of five ILTV strains. Sequences were also compared to reveal the similarity of strains across time and to discriminate between wild-type and vaccine strains. Genomes of three ILTV field isolates from outbreaks occurred in Italy in 1980, 2007 and 2011, and two commercial chicken embryo origin (CEO) vaccines were sequenced using the 454 Life Sciences technology. The comparison with the Serva genome showed that 35 open reading frames (ORFs) differed across the five genomes. Overall, 54 single nucleotide polymorphisms (SNPs) and 27 amino acid differences in 19 ORFs and two insertions in the UL52 and ORFC genes were identified. Similarity among the field strains and between the field and the vaccine strains ranged from 99.96% to 99.99%. Phylogenetic analysis revealed a close relationship among them, as well. This study generated data on genomic variation among Italian ILTV strains revealing that, even though the genetic variability of the genome is well conserved across time and between wild-type and vaccine strains, some mutations may help in differentiating among them and may be involved in ILTV virulence/attenuation. The results of this study can contribute to the understanding of the molecular bases of ILTV pathogenicity and provide genetic markers to differentiate between wild-type and vaccine strains. PMID- 26890527 TI - Slope Transit Time (STT): A Pulse Transit Time Proxy requiring Only a Single Signal Fiducial Point. AB - A novel pulse transit time proxy measurement, slope transit time (STT), is proposed in this letter. STT is based on geometrical considerations of the arriving photoplethysmographic cardiac waveform and its computation requires only the measurement of a single point on each cardiac beat arriving at the peripheral site. This novel transit time is explained conceptually and its implementation illustrated through its application to signals from respiratory effort, Muller maneuver, and obstructive sleep apnea trials. PMID- 26890528 TI - Computer-Aided Endoscopic Diagnosis Without Human-Specific Labeling. AB - GOAL: Most state-of-the-art computer-aided endoscopic diagnosis methods require pixelwise labeled data to train various supervised machine learning models. However, it is a tedious and time-consuming work to collect sufficient precisely labeled image data. Fortunately, we can easily obtain huge endoscopic medical reports including the diagnostic text and images, which can be considered as weakly labeled data. METHODS: In this paper, our motivation is to design a new computer-aided endoscopic diagnosis system without human specific labeling; in comparison with most state of the arts, ours only depends on the endoscopic images with weak labels mined from the diagnostic text. To achieve this, we first cast the endoscopic image folder and included images as bag and instances and represent each instance based on the global bag-of-words model. We then adopt a feature mapping scheme to represent each bag by mining the most suspicious lesion instance from each positive bag automatically. In order to achieve self-online updating from sequential new coming data, an online metric learning method is used to optimize the bag-level classification. RESULTS: Our computer-aided endoscopic diagnosis system achieves an AUC of 0.93 on a new endoscopic image dataset captured from 424 volunteers with more than 12k images. CONCLUSION: The system performance outperforms other state of the arts when we mine the most positive instances from positive bags and adopt the online phase to mine more information from the unseen bags. SIGNIFICANCE: We present the first weakly labeled endoscopic image dataset for computer-aided endoscopic diagnosis and a novel system that is suitable for use in clinical settings. PMID- 26890526 TI - DNA methylation variation of human-specific Alu repeats. AB - DNA methylation is the major repression mechanism for human retrotransposons, such as the Alu family. Here, we have determined the methylation levels associated with 5238 loci belonging to 2 Alu subfamilies, AluYa5 and AluYb8, using high-throughput targeted repeat element bisulfite sequencing (HT-TREBS). The results indicate that ~90% of loci are repressed by high methylation levels. Of the remaining loci, many of the hypomethylated elements are found near gene promoters and show high levels of DNA methylation variation. We have characterized this variation in the context of tumorigenesis and interindividual differences. Comparison of a primary breast tumor and its matched normal tissue revealed early DNA methylation changes in ~1% of AluYb8 elements in response to tumorigenesis. Simultaneously, AluYa5/Yb8 elements proximal to promoters also showed differences in methylation of up to one order of magnitude, even between normal individuals. Overall, the current study demonstrates that early loss of methylation occurs during tumorigenesis in a subset of young Alu elements, suggesting their potential clinical relevance. However, approaches such as deep bisulfite-sequencing of individual loci using HT-TREBS are required to distinguish clinically relevant loci from the background observed for AluYa5/Yb8 elements in general with regard to high levels of interindividual variation in DNA methylation. PMID- 26890529 TI - A Quaternion Weighted Fourier Linear Combiner for Modeling Physiological Tremor. AB - GOAL: This paper offers a new approach to model physiological tremor aiming at attenuating undesired vibrations of the tip of microsurgical instruments. METHOD: Several tremor modeling algorithms, such as the weighted Fourier linear combiner (wFLC), have proved effective. They, however, treat the three-dimensional (3-D) tremor signal as three independent 1-D signals in the x-, y-, and z-axes. In addition, the force f by which a surgeon holds the instrument has never been taken into account in modeling. Hence, conventional algorithms are inherently blind to any potential multidimensional couplings. RESULTS: We first show that there exists statistically significant subject- and task-dependent coherence between data in the x-, y-, z -, and f-axes. We hypothesize that a filter that models the tremor in 4-D ( x , y, z, and f ) yields a more accurate model of tremor. We, therefore, developed a quaternion version of the wFLC algorithm and termed it QwFLC. We tested the proposed QwFLC algorithm with real physiological tremor data that were recorded from five novice subjects and four experienced microsurgeons. Although compared to wFLC, QwFLC requires six times larger computational resources, we showed that QwFLC can improve the modeling by up to 67% and that the improvement is proportional to the total coherence between the tremor in xyz and the force signal. CONCLUSION: By taking into account interactions of the 3-D tremor and the force data, the tremor modeling performance enhances significantly. PMID- 26890533 TI - The changing 'face' of wait-listed patients in the USA. PMID- 26890530 TI - A Probabilistic Analysis of Muscle Force Uncertainty for Control. AB - BACKGROUND: We control the movements of our body and limbs through our muscles. However, the forces produced by our muscles depend unpredictably on the commands sent to them. This uncertainty has two sources: irreducible noise in the motor system's processes (i.e., motor noise) and variability in the relationship between muscle commands and muscle outputs (i.e., model uncertainty). Any controller, neural or artificial, benefits from estimating these uncertainties when choosing commands. METHODS: To examine these benefits, we used an experimental preparation of the rat hindlimb to electrically stimulate muscles and measure the resulting isometric forces. We compare a functional electric stimulation (FES) controller that represents and compensates for uncertainty in muscle forces with a standard FES controller that neglects uncertainty. RESULTS: Accounting for uncertainty substantially increased the precision of force control. CONCLUSION: Our study demonstrates the theoretical and practical benefits of representing muscle uncertainty when computing muscle commands. SIGNIFICANCE: The findings are relevant beyond FES as they highlight the benefits of estimating statistical properties of muscles for both artificial controllers and the nervous system. PMID- 26890532 TI - Optical Input/Electrical Output Memory Elements based on a Liquid Crystalline Azobenzene Polymer. AB - Responsive polymer materials can change their properties when subjected to external stimuli. In this work, thin films of thermotropic poly(metha)acrylate/azobenzene polymers are explored as active layer in light programmable, electrically readable memories. The memory effect is based on the reversible modifications of the film morphology induced by the photoisomerization of azobenzene mesogenic groups. When the film is in the liquid crystalline phase, the trans -> cis isomerization induces a major surface reorganization on the mesoscopic scale that is characterized by a reduction in the effective thickness of the film. The film conductivity is measured in vertical two-terminal devices in which the polymer is sandwiched between a Au contact and a liquid compliant E GaIn drop. We demonstrate that the trans -> cis isomerization is accompanied by a reversible 100-fold change in the film conductance. In this way, the device can be set in a high- or low-resistance state by light irradiation at different wavelengths. This result paves the way toward the potential use of poly(metha)acrylate/azobenzene polymer films as active layer for optical input/electrical output memory elements. PMID- 26890534 TI - Efficacy of MLC601 on functional recovery after stroke: A systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND AND PURPOSE: Traditional Chinese medicine (TCM) MLC601 has shown promising results on functional recovery of patients after stroke. This study aimed to evaluate the pooled effect of its efficacy. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs) assessing efficacy of MLC601 vs other TCM compounds or placebo. The pooled effect was the relative risk (RR) combined by random effects model. A prediction effect interval was estimated for new studies and a cumulative meta-analysis was performed. RESULTS: Four studies comprising five RCTs were included. The pooled RR was 1.64 (95% CI = 1.05 2.57; p-value = 0.031) favouring MLC601, but heterogeneity was large (I(2) = 80%; Q-test p-value = 0.0005). Therefore, the prediction interval was wide and consistent with a null effect (RR range = 0.36-7.45). The cumulative meta analysis showed a decreasing pattern of effect size through time, with higher effects for trials comparing MLC601 vs other TCM and a systematic decrease of the pooled effect when including later trials comparing MLC601 vs placebo. CONCLUSIONS: Evidence on the efficacy of MLC601 has decreased over time and when the comparison arm is placebo instead of other TCM compound. Current evidence suggests MLC601 does not outperform placebo on functional recovery after stroke. PMID- 26890535 TI - Trait and State Variance in Multi-Informant Assessments of ADHD and Academic Impairment in Spanish First-Grade Children. AB - OBJECTIVE: We examined the stable trait and variable state components of ADHD inattention (IN), ADHD-hyperactivity/impulsivity (HI), and academic impairment (AI) dimensions using mothers', fathers', primary and secondary teachers' ratings of children's behavior at home and school. We also examined between-informant agreement with regard to trait and state components. METHOD: Mothers, fathers, primary and secondary teachers rated HI, IN, and AI in N = 758 Spanish first grade children (55% boys) over three measurement occasions across 12 months. RESULTS: Latent state-trait analyses revealed that mothers', fathers', and primary teachers' (but not secondary teachers') ratings reflected more trait variance for ADHD-HI (M = 73%), ADHD-IN (M = 74%), and AI (M = 76%) than occasion specific variance (M = 27%, M = 26%, and M = 24%, respectively). Fathers' ratings shared a meaningful level of trait variance with mothers' ratings of ADHD-HI and ADHD-IN (range 78% to 82%), whereas primary and secondary teachers' ratings shared lower levels of trait variance with mothers' ratings (range 41% to 63%). The trait components of fathers', primary teachers', and secondary teachers' ratings of AI showed high levels of convergence with mothers' ratings (88%, 70%, and 59% respectively). CONCLUSIONS: ADHD symptom reports reflect both trait (48 to 86%) and state (14 to 53%) variance components. The lower amount of shared variability between home and school suggests the setting-specificity of trait and state components of ADHD symptoms. Our findings indicate that ADHD symptom reports may reflect context-specific traits, suggesting the importance of differentiating and targeting ADHD behaviors across different settings. PMID- 26890536 TI - Is laparoscopic live donor hepatectomy justified ethically? AB - Live donor liver transplant (LDLT) was first reported in the 1990s and quickly raised ethical considerations, mainly related to the risk brought to the donor. The question of donor safety was even more accurate with the occurrence of laparoscopy, a technique which could allegedly increase the risk of severe intraoperative complications. Besides the questions of justice and autonomy, donor safety remains the main ethical debate of LDLT. Considering the lack of comparative assessment of postoperative outcomes, the Jury of the last Consensus meeting held in Japan in 2014 called for the creation of international registries to help to determine the benefit/risk ratio of laparoscopic donor hepatectomy. Since randomized studies are very unlikely to occur, benchmarking comparisons, between liver and kidney donors for instance, may also help to define standard practice. At last, donors' points of view should also be taken into account in the evaluation of those innovative procedures. PMID- 26890538 TI - Multiple Gongylonema pulchrum worms in a human esophagus. PMID- 26890537 TI - The impact of introducing biologics to patients with rheumatoid arthritis in Taiwan: a population-based trend study. AB - AIM: The biologics used to treat rheumatoid arthritis (RA) patients with a catastrophic illness certificate have been free without co-payment since 2003 in Taiwan. The purpose of this study was to explore the trend of health care expenditures and the cost of biologics for the treatment of RA patients between 1999 and 2009. METHODS: This study used a specially requested nation-wide RA patient claim dataset from National Health Insurance program. We identified all patients by both the primary diagnosis code ICD-9-CM 714.0 and the catastrophic illness certificate for RA. A total of 30 013 patients were recorded in the treated RA cohort from 1999 to 2009.The growth rates before and after introducing biologics were compared and tested. RESULTS: We found that from 1999 to 2009 the adjusted incidence rate for RA stably increased. Drug costs accounted for 53.2 70.3% of the total medical cost during the study period. There was a significant increase in biologics cost, climbing rapidly from 2.8% in 2003 to 60.4% of the total drug cost in 2009. The growth rate of outpatient drug costs was much higher after the introduction of biologics (2003-2009), which was 207.8% versus 42.0% as compared to the earlier period (1999-2002). Biologics such as etanercept, adalimumab and rituximab, were the crucial factors responsible for this increase in drug cost. CONCLUSIONS: The financial impact of adopting new biologics on healthcare costs is a critical issue that needs to be addressed by the National Health Insurance. PMID- 26890539 TI - Simultaneous side-by-side self-expanding metal stent placement using a two channel endoscope for a bilioenteric stricture after Child's resection. PMID- 26890540 TI - Serrated polyposis syndrome: a silent killer when undetected. PMID- 26890541 TI - Robotic double-loop reconstruction method following total gastrectomy. PMID- 26890542 TI - Endoscopic submucosal dissection of a nonpolypoid superficial neoplasm of the terminal ileum. PMID- 26890543 TI - Over-the-scope clip-assisted endoscopic full-thickness resection after incomplete resection of rectal adenocarcinoma. PMID- 26890544 TI - Obscure gastrointestinal bleeding caused by intestinal lipomatosis: double balloon endoscopic and laparoscopic views. PMID- 26890545 TI - Endoscopic Zenker diverticulotomy using the window technique: a technical trick to improve the field of view. PMID- 26890546 TI - Extracorporeal shock wave lithotripsy allows successful endoscopic removal of a fractured stone basket trapped in the pancreatic duct. PMID- 26890547 TI - "Underwater" endoscopic submucosal dissection: a novel technique for complete resection of a rectal neuroendocrine tumor. PMID- 26890548 TI - Endoscopic resection of a giant esophageal fibrovascular polyp. PMID- 26890549 TI - Endoscopic ultrasound-guided transesophageal pericardiocentesis: an alternative approach to a pericardial effusion. PMID- 26890550 TI - Transversal spin freezing and re-entrant spin glass phases in chemically disordered Fe-containing perovskite multiferroics. AB - We propose experimental verification and theoretical explanation of magnetic anomalies in the complex Fe-containing perovskite multiferroics like PbFe1/2Nb1/2O3 and PbFe1/2Ta1/2O3. The theoretical part is based on our model of coexistence of the long-range magnetic order and spin glass in the above compounds. In our model, the exchange interaction is anisotropic, coupling antiferromagnetically z spin components of Fe(3+) ions. At the same time, the xy components are coupled by much weaker exchange interaction of ferromagnetic sign. In the system with spatial disorder (half of the corresponding lattice sites are occupied by spinless Nb(5+) ions) such frustrating interaction results in the fact that the antiferromagnetic order is formed by the z projection of the spins, while their xy components contribute to spin glass behaviour. Our theoretical findings are supported by the experimental evidence of such a coexistence of antiferromagnetic and spin glass phases in chemically disordered Fe-containing complex perovskite multiferroics. PMID- 26890551 TI - Imaging Membrane Potential with Two Types of Genetically Encoded Fluorescent Voltage Sensors. AB - Genetically encoded voltage indicators (GEVIs) have improved to the point where they are beginning to be useful for in vivo recordings. While the ultimate goal is to image neuronal activity in vivo, one must be able to image activity of a single cell to ensure successful in vivo preparations. This procedure will describe how to image membrane potential in a single cell to provide a foundation to eventually image in vivo. Here we describe methods for imaging GEVIs consisting of a voltage-sensing domain fused to either a single fluorescent protein (FP) or two fluorescent proteins capable of Forster resonance energy transfer (FRET) in vitro. Using an image splitter enables the projection of images created by two different wavelengths onto the same charge-coupled device (CCD) camera simultaneously. The image splitter positions a second filter cube in the light path. This second filter cube consists of a dichroic and two emission filters to separate the donor and acceptor fluorescent wavelengths depending on the FPs of the GEVI. This setup enables the simultaneous recording of both the acceptor and donor fluorescent partners while the membrane potential is manipulated via whole cell patch clamp configuration. When using a GEVI consisting of a single FP, the second filter cube can be removed allowing the mirrors in the image splitter to project a single image onto the CCD camera. PMID- 26890552 TI - The impact of low-dose aspirin on preterm birth: secondary analysis of a randomized controlled trial. AB - OBJECTIVE: The objective of this study is to determine whether low-dose aspirin (LDA) reduced the rate of preterm birth (PTB) in a cohort of women at high risk for preeclampsia. STUDY DESIGN: Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin trial. Preterm births were categorized by phenotype: indicated, spontaneous or due to preterm premature rupture of membranes (PPROMs). RESULTS: Of 1789 randomized women, 30.5% delivered before 37 weeks (18.5% indicated, 5.8% spontaneous and 6.2% following preterm PPROMs). Among women randomized to LDA, we observed a trend favoring fewer PTBs due to spontaneous preterm labor and preterm PPROMs, odds ratio (OR: 0.826 (0.620, 1.099)); the incidence of indicated PTBs appeared unchanged, OR: 0.999 (0.787, 1.268). CONCLUSION: Although not reaching significance, we observed an effect size similar to other studies of both low- and high-risk women. These results support findings from other studies assessing LDA as a PTB prevention strategy. PMID- 26890553 TI - Hemodynamic reference for neonates of different age and weight: a pilot study with electrical cardiometry. AB - OBJECTIVE: Electrical cardiometry (EC) is an impedance-based monitor that provides noninvasive, real-time hemodynamic assessment. However, the reference values for neonates have not been established. STUDY DESIGN: EC (Aesculon) was applied to hemodynamically stable preterm and term infants. Hemodynamic variables included cardiac output (CO), cardiac index (CI), stroke volume (SV) and heart rate (HR). Their gestational age (GA), weight and body surface area (BSA) were recorded. RESULTS: A total of 280 neonates were studied. Their GA ranged from 26(5/7) to 41(4/7) weeks, weight 800 to 4420 g and BSA 0.07 to 0.26 m(2). CO was positively correlated to GA, weight and BSA (r=0.681, 0.822, 0.830, respectively; all P<0.001). Using regression analysis, CO was most significantly correlated to BSA. Mean CI was 2.55+/-0.37 l min(-1) per m(2). CONCLUSION: Hemodynamic reference by EC is notably distinct among neonates of diverse maturity. CO is most closely correlated to BSA. PMID- 26890554 TI - Effects of standardized acoustic stimulation in premature infants: a randomized controlled trial. AB - OBJECTIVE: The objective of this study was to investigate the effects of recorded lullabies and taped maternal voice in premature infants. STUDY DESIGN: Sixty-two preterm infants in a stable condition with 30<37 weeks of gestation and <10 days of postnatal age were randomly assigned to hear (A) recorded lullabies or (B) taped maternal voice for 30 min each evening during 14 consecutive days or (C) receive no standardized acoustic stimulation (control group). Heart rate and respiratory rate were recorded daily before, during and after the intervention (A and B) or a comparable period with no intervention (C), whereas activity was measured on days 1, 7 and 14 of the intervention using accelerometers. RESULTS: Both interventions led to a significant decrease in heart rate and respiratory rate during and after the stimulation when compared with the control group. The changes were more pronounced in infants with higher gestational ages (P=0.001). Lower activity was measured during the intervention when compared with the control group (P<0.01). CONCLUSIONS: Standardized acoustic stimulation with recorded lullabies and taped maternal voice led to a decrease in heart rate and respiratory rate, and was associated with lower activity. Whether this indicates a reduced stress reaction needs to be investigated in further studies. PMID- 26890555 TI - Response to dopamine in prematurity: a biomarker for brain injury? AB - OBJECTIVE: To identify factors associated with responsiveness to dopamine therapy for hypotension and the relationship to brain injury in a cohort of preterm infants. STUDY DESIGN: The pharmacy database at St Louis Children's Hospital was retrospectively queried to identify infants who (a) were born <28 weeks gestation between 2012 and 2014, (b) received dopamine and (c) had blood pressure measurements from an umbilical arterial catheter. A control group was constructed from contemporaneous infants who did not receive dopamine. Mean arterial blood pressure (MABP) at baseline, 1 h and 3 h after initiating dopamine were obtained for each dopamine-exposed infant. MABP measurements at matched time points were obtained in the control group. RESULT: Sixty-nine dopamine-treated and 45 control infants were included. Mean DeltaMABP at 3 h was 4.5+/-6.3 mm of Hg for treated infants vs 1+/-2.9 for the control. Median dopamine starting dose was 2.5 MUg kg( 1) min(-1). Dopamine-treated infants were less mature and of lower birth weight while also more likely to be intubated at 72 h, diagnosed with intraventricular hemorrhage (IVH) and to die. Failure to respond to dopamine was associated with greater likelihood of developing IVH (odds ratio (OR) 5.8, 95% confidence interval (CI) 1.1-42.3), while a strong response (DeltaMABP>10 mm Hg) was associated with a reduction in risk of IVH (OR 0.1, 95% CI 0.01-0.8). CONCLUSION: Low-moderate dose dopamine administration results in modest blood pressure improvements. A lack of response to dopamine is associated with a greater risk of IVH, whereas a strong response is associated with a decreased risk. Further research into underlying mechanisms and management strategies is needed. PMID- 26890556 TI - Factors associated with high-risk rural women giving birth in non-NICU hospital settings. AB - OBJECTIVE: To identify risk factors for childbirth in a facility without neonatal intensive care unit (NICU) capacity among high-risk rural women. STUDY DESIGN: Using data on all maternal hospitalizations for rural residents in nine states (2010, 2012), we performed logit regression, focusing on women with multiple gestation and preterm birth. We defined a 'local' hospital as any maternity hospital within 30 miles (or the nearest hospital). RESULTS: Rural women with preterm births and multiple gestation pregnancies were less likely to give birth in a hospital with NICU capacity if no local hospital had this capacity. Adjusted odds of giving birth in a NICU hospital were lower among women ?age 20 (AOR 0.87 (95% CI 0.77, 0.98)), Medicaid beneficiaries (0.81 (0.75, 0.89)), uninsured women (0.44 (0.32, 0.61)) and black women (0.60 (0.50, 0.71)). CONCLUSIONS: Among high risk rural pregnant women without local NICU access, younger, low-income, and black women had lower odds of using NICU hospitals. PMID- 26890558 TI - Circumferential strain of carotid arteries does not differ between patients with advanced coronary artery disease and group without coronary stenoses. AB - PURPOSE: Speckle tracking echocardiography is widely used for the analysis of myocardial function. Recently, circumferential strain (CS) of carotid arteries was postulated as novel indicator of vascular function. Our aim was to characterize and compare CS of carotid arteries in patients with advanced coronary artery disease and controls without significant coronary stenoses. PATIENTS/METHODS: We compared CS of both common carotid arteries (CCA) in the 25 patients with three-vessel coronary artery disease (3VD) (mean age 69+/-9 years, 9 male) and in 16 age-matched subjects without significant coronary lesions (C) (69+/-8 years, 7 male). Additionally in 11 patients we estimated pulse wave velocity (PWV) and assessed the correlation between PWV and CS. Short-axis images of arteries were acquired for strain analysis with linear probe of echocardiograph. The assessment of CS was performed off-line by two observers. RESULTS: The intraobserver variability for the CS (coefficient of variation) were 4.9 and 5.4% for left and right CCA and interobserver variability were 11.7% and 12.5%, respectively. The mean CS for left and right CCA did not differ between compared groups. We did not find correlation between CS strain and PWV. The only difference was related to the more prevalent plaque presence and thicker intima media complex (IMT) in 3VD (p=0.0039 for IMT of left CCA and p=0.016 for IMT of right CCA). CONCLUSIONS: The global CS of CCA, contrary to IMT, did not allow for differentiation between 3VD and C subjects. Despite good feasibility and concordance of CS measurements its clinical significance remains to be established. PMID- 26890557 TI - Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study. AB - OBJECTIVE: The objective of this study was to assess the association between apolipoprotein E (apoE) genotype and preterm birth (PTB) and small for gestational age (SGA). STUDY DESIGN: ApoE phenotyping was performed on 680 women linked to 1065 births. Allele frequencies were compared and PTB and SGA risk was estimated using log-binomial regression. RESULTS: The E2 allele was more common in SGA births (P<0.01). SGA risk was increased among E2 carriers compared with genotype E3/E3, though associations were attenuated following adjustment for maternal age, education, race, smoking and prenatal visits. Stronger associations were observed for term SGA (first birth: adjusted relative risk (aRR)=1.78, 95% confidence interval (CI) 1.06 to 2.98; any birth: aRR=1.52, 95% CI 0.96 to 2.40) and among whites specifically (first: aRR=2.88, 95% CI 1.45 to 5.69; any: aRR=2.75, 95% CI 1.46 to 5.22). CONCLUSIONS: Associations between maternal apoE genotype and SGA may represent decreased fetal growth in women with lower circulating cholesterol levels. PMID- 26890560 TI - Impact of Autism Navigator on Access to Services. AB - OBJECTIVE: To determine whether access to an Autism Patient Navigator (APN) for children diagnosed with autism spectrum disorder (ASD) at <48 months of age would be useful and lead to more appointments with needed services. METHOD: Participants included parents of 39 children diagnosed with ASD in a multidisciplinary clinic. After diagnosis, the patients were randomized to 4 groups: Medicaid early (n = 9) or late support (n = 9) and non-Medicaid early (n = 11) or late support (n = 10). Early access to the APN was at the family meeting and later at 3 months after diagnosis. Data included demographic information and completion by phone interview at 3 months postdiagnosis of a questionnaire on the usefulness of the assessment and parent's desire or ability to obtain recommended services. RESULTS: Demographically, the groups were not different. Children were most frequently male, white, non-Hispanic, and non-Medicaid with a mean age of 35 months. In comparison with the non-Medicaid groups, the Medicaid groups more often endorsed the 9 questions on the usefulness of the assessment as being "A Great Deal" useful (p = .022). Groups with early support were more successful in scheduling or completing appointments for recommended services overall including medical, educational, therapeutic, and parent resource appointments (p = .031). Barriers to services or resources were reported by 35.9%. CONCLUSION: Parents of young children with Medicaid with a recent diagnosis of ASD found the assessment "very useful" compared with non-Medicaid group. The groups with immediate access to an APN were more successful with scheduling and completing appointments. PMID- 26890559 TI - Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease. AB - OBJECTIVE: The negative impact of end-stage kidney disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). METHOD: Participants included 124 preschool children with mild to moderate CKD, aged 12 to 68 months (median = 3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 mL.min.1.73 m. In addition to level of function and percent of participants scoring >=1 SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, and abnormal birth history), and developmental level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. RESULTS: Median scores for all measures were in the average range; however, 27% were deemed at risk for a developmental level/IQ <85, 20% were at-risk for attention variability, and parent ratings indicated 30% and 37% to be at risk for executive dysfunction and adaptive behavior problems, respectively. Approximately 43% were deemed at risk on 2 or more measures. None of the disease-related variables were significantly associated with these outcomes, although the presence of hypertension approached significance for attention variability (p < .09). Abnormal birth history and lower maternal education were significantly related to lower developmental level/IQ; seizures were related to lower parental ratings of executive function and adaptive behavior; and abnormal birth history was significantly related to lower ratings of adaptive behavior. When predicting risk status, the logistic regression did evidence both higher GFR and the lack of anemia to be associated with more intact developmental level/IQ. CONCLUSION: These findings suggest relatively intact functioning for preschool children with mild to moderate CKD, but the need for ongoing developmental surveillance in this population remains warranted, particularly for those with abnormal birth histories, seizures, and heightened disease severity. PMID- 26890561 TI - Early Predictors of Childhood Restrictive Eating: A Population-Based Study. AB - OBJECTIVE: Childhood eating problems, in particular restrictive eating, are common. Knowledge and understanding of risk mechanisms is still scarce. We aimed to investigate prospective early risk factors for restrictive eating across child, maternal, obstetric, and sociodemographic domains in a population-based sample of Danish 5 to 7 year olds. METHOD: Data on restrictive eating patterns (picky eating, slow/poor eating, and emotional undereating) collected on 1327 children from the Copenhagen Child Cohort 2000 were linked with registered and routinely collected health nurse data (during the first year of life). Prospective risk factors were investigated in univariable and multivariable regression models. RESULTS: Feeding problems in infancy were prospectively associated with childhood picky eating (odds ratio [OR] = 2.02, 95% confidence interval [CI], 1.20-3.40) and emotional undereating (OR = 1.49, 95% CI, 1.05 2.11). A high thriving index in infancy was inversely associated with both picky and slow/poor eating. Having 2 non-Danish-born parents predicted slow/poor eating (OR = 5.29, 95% CI, 1.16-24.09) in multivariable analyses, as did maternal diagnosis of a psychiatric disorder before child age 5 years in univariable analyses (OR = 6.08, 95% CI, 1.70-21.72). CONCLUSIONS: Feeding problems and poor growth in the first year of life show high continuity into childhood restrictive eating. Maternal psychopathology is an important and modifiable risk factor. These findings confirm that early signs of poor eating and growth are persistent and might be useful in predicting eating problems in mid-childhood. PMID- 26890563 TI - Transportation-Related Safety Behaviors in Top-Grossing Children's Movies from 2008 to 2013. AB - OBJECTIVE: Children regularly imitate behavior from movies. The authors assessed injury risk behaviors in top-grossing children's films. METHODS: The 5 top grossing G- or PG-rated movies annually from 2008 to 2013 were included, including animated movies and those set in the past/future. Researchers coded transportation scenes for risk taking in 3 domains: protection/equipment, unsafe behaviors, and distraction/attention. RESULTS: Safe and risky behaviors were recorded across the 3 domains. With regard to protection and equipment, 20% of motor vehicle scenes showed characters riding without seat belts and 27% of scenes with motorcycles showed characters riding without helmets. Eighty-nine percent of scenes with horses showed riders without helmets and 67% of boat operators failed to wear personal flotation devices. The most common unsafe behaviors were speeding and unsafe street-crossing. Twenty-one percent of scenes with motor vehicles showed drivers speeding and 90% of pedestrians in films failed to wait for signal changes. Distracted and inattentive behaviors were rare, with distracted driving of motor vehicles occurring in only approximately 2% of total driving scenes. CONCLUSION: Although many safe transportation behaviors were portrayed, the film industry continues to depict unsafe behaviors in movies designed for pediatric audiences. There is a need for the film industry to continue to balance entertainment and art with modeling of safe behavior for children. PMID- 26890562 TI - Youth Screen Time and Behavioral Health Problems: The Role of Sleep Duration and Disturbances. AB - OBJECTIVE: The purpose of this study was to examine the indirect effect of youth screen time (e.g., television, computers, smartphones, video games, and tablets) on behavioral health problems (i.e., internalizing, externalizing, and peer problems) through sleep duration and disturbances. METHODS: The authors assessed a community sample of parents with a child in one of the following three developmental stages: young childhood (3-7 yrs; N = 209), middle childhood (8-12 yrs; N = 202), and adolescence (13-17 yrs; N = 210). Path analysis was used to test the hypothesized indirect effect model. RESULTS: Findings indicated that, regardless of the developmental stage of the youth, higher levels of youth screen time were associated with more sleep disturbances, which, in turn, were linked to higher levels of youth behavioral health problems. CONCLUSION: Children who have increased screen time are more likely to have poor sleep quality and problem behaviors. PMID- 26890565 TI - Characterization of the Oxygen Binding Motif in a Ruthenium Water Oxidation Catalyst by Vibrational Spectroscopy. AB - For homogeneous mononuclear ruthenium water oxidation catalysts, the Ru-O2 complex plays a crucial role in the rate determining step of the catalytic cycle, but the exact nature of this complex is unclear. Herein, the infrared spectra of the [Ru(tpy)(bpy)(O2)](2+) complex (tpy=2,2':6',2''-terpyridine; bpy=2,2' bipyridine) are presented. The complex [Ru(tpy)(bpy)(O2)](2+), formed by gas phase reaction of [Ru(tpy)(bpy)](2+) with molecular O2, was isolated by using mass spectrometry and was directly probed by cryogenic ion IR predissociation spectroscopy. Well-resolved spectral features enable a clear identification of the O-O stretch using (18) O2 substitution. The band frequency and intensity indicate that the O2 moiety binds to the Ru center in a side-on, bidentate manner. Comparisons with DFT calculations highlight the shortcomings of the B3LYP functional in properly depicting the Ru-O2 interaction. PMID- 26890566 TI - Reply. PMID- 26890567 TI - Associations of growth patterns and islet autoimmunity in children with increased risk for type 1 diabetes: a functional analysis approach. AB - BACKGROUND: Several studies indicate associations between early growth and type 1 diabetes (T1D). However, it remains an open question whether these findings can be translated to typical growth patterns associated with increased risk for T1D associated islet autoimmunity. METHODS: We analyzed pooled data from 2236 children followed up in two large prospective German birth cohorts with a genetically increased risk for T1D including 18 564 measurements of height and weight, which were transformed to sex- and age-specific standard deviation scores (SDS). A total of 191 children developed any islet autoantibodies, 101 multiple islet autoantibodies. We applied a model-based clustering technique to derive typical height and body mass index (BMI) growth patterns, stratified for maternal T1D status. These patterns were used to predict islet autoimmunity in logistic regression models, adjusted for potential confounders. RESULTS: Growth patterns were not associated with islet autoimmunity in the whole dataset and in children of diabetic mothers, respectively. In children of non-diabetic mothers ,however, islet autoimmunity was associated with rapidly increasing BMI SDS values until the age of 3 yr [adjusted odds ratio (95% confidence interval): 2.02 (1.03, 3.73) for development of any islet autoantibodies) and with consistently above average height SDS values [odds ratio: 2.21 (1.15, 4.17)]. In contrast, a pattern of high height SDS values at birth followed by a decrease to average values after 3 yr was associated with a reduced rate of islet autoimmunity [odds ratio: 0.16 (0.01, 0.62)]. CONCLUSION: Early growth patterns may be associated with T1D-related islet autoimmunity risk in children of non-diabetic mothers. PMID- 26890568 TI - Logic Gate Operation by DNA Translocation through Biological Nanopores. AB - Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs "1" and "0" as single-stranded DNA (ssDNA) that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND) operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment. PMID- 26890570 TI - High Serum Sclerostin Levels Are Associated with a Better Outcome in Haemodialysis Patients. AB - BACKGROUND: Sclerostin is an osteocyte hormone that decreases osteoblastogenesis. Sclerostin may play a key role in osteoporosis and also in vascular calcification (VC). In chronic kidney disease and haemodialysis (HD) patients, serum sclerostin levels are high. AIM: To assess the correlation of serum sclerostin levels with VC, bone mineral density (BMD), and survival rate in HD patients. METHODS: A cross-sectional study was conducted in prevalent HD patients to correlate serum sclerostin tertiles with the Kauppila aortic calcification score, BMD scores and survival rate. RESULTS: We studied 207 patients who had a mean serum sclerostin level of 1.9 +/- 0.7 ng/ml. Compared to patients in the 1st tertile of serum sclerostin levels (0.6-1.53 ng/ml), patients in the 3rd tertile (2.2-4.6 ng/ml) were significantly older (73.7 +/- 12 vs. 64.7 +/- 18 years), more frequently of the male gender (74 vs. 48%), had lower serum bone-specific alkaline phosphatases values (14 +/- 9 vs. 20.4 +/- 13 ug/l), were less frequently treated with alfacalcidol, displayed lower aortic calcification scores (9.5 +/- 5 vs. 12.5 +/- 7/24) and had higher BMD scores. Furthermore, patients of the 3rd tertile displayed a lower mortality rate compared to tertile 1 using multivariable adjusted Cox model (hazard ratio 0.5, 95% CI 0.25-0.93, p = 0.03). The main factors associated with VC score were age, diabetes, cardiovascular disease, CRP level and Warfarin use. CONCLUSION: Our study of HD patients shows that higher serum sclerostin levels are associated with higher BMD, lower aortic calcification scores, and a better survival rate. PMID- 26890569 TI - Hirsutella sinensis Attenuates Aristolochic Acid-Induced Renal Tubular Epithelial Mesenchymal Transition by Inhibiting TGF-beta1 and Snail Expression. AB - OBJECTIVE: To investigate the inhibitory effect of Hirsutella sinensis (HS) on epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells induced by aristolochic acid (AA) and its possible mechanism. METHODS: 18 male Sprague Dawley rats were randomly and equally divided into the following 3 groups: AA group, AA+HS group and control group. Urinary protein excretion and creatinine clearance (CCr) were measured. All rats were sacrificed at the end of 12th week. The pathological examination of renal tissue was performed and the mRNA and protein expression of transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (alpha-SMA), cytokeratin-18 and Snail in renal cortex were determined by real time quantitative PCR and immunohistochemical staining respectively. In addition, human renal proximal tubule epithelial cells line (HKC) was divided into the following 4 groups: AA group, AA+HS group, HS control group and control group. The above mRNA and protein expression in HKC was determined by real time quantitative PCR and Western blot respectively. RESULTS: (1) CCr was significantly decreased, and the urinary protein excretion and relative area of renal interstitial fibrosis were significantly increased in the rats of AA and AA+HS group compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly lightened in the rats of AA+HS group compared to those in AA group (P<0.05). (2) The mRNA and protein expression of TGF-beta1, alpha-SMA and Snail was significantly up-regulated and the expression of cytokeratin-18 was significantly down-regulated in the rat renal cortex as well as in the cultured HKC cells in AA and AA+HS groups compared to those in control group (P<0.05 or P<0.01); all the above abnormalities significantly alleviated in AA+HS group compared to those in AA group (P<0.05 or P<0.01). (3) Knockdown endogenous Snail expression by siRNA could ameliorate AA-induced EMT of HKC cells, while overexpression of Snail by plasmid transfection diminished the antagonistic effect of HS on AA-induced EMT. These results suggest Snail might be a potential target of HS effect. CONCLUSION: HS is able to antagonize, to some extent, tubular EMT and renal interstitial fibrosis caused by AA, which might be related to its inhibitory effects on the TGF-beta1 and Snail expression. PMID- 26890571 TI - Relationship between uric acid levels and progressive supranuclear palsy. AB - INTRODUCTION: The pathophysiology of both PD and PSP is characterized by a pro oxidant state. Uric acid is an oxidative stress marker. High uric acid blood levels have been associated with a reduced risk of PD and a decreased rate of disease progression. We investigated whether a low serum concentration of uric acid is also associated with PSP. METHODS: We measured serum uric acid concentrations in a subsample of the ENGENE PSP Cohort that included 75 cases and 75 frequency-matched-by-sex healthy controls (69 spouses, 6 in-laws) from four centers willing to participate (Case Western, Rush University, University of Utah, and University of Louisville). Case severity was characterized using the total PSP-Rating Scale, UPDRS, and Mattis Dementia Rating Scale. Unconditional logistic regression, Pearson's chi-squared test, and analysis of variance were used, as appropriate. RESULTS: The mean uric acid level among cases (4.0 mg/dL) was not significantly lower than that of controls (4.1 mg/dL). When controlling for sex, there were no between-group statistical differences in uric acid levels. Uric acid levels were not correlated with disease severity. CONCLUSIONS: The results of this study do not provide evidence of uric acid having a protective role in PSP, even if oxidative injury is important in the pathophysiology of this disorder. The lack of statistical significance suggests that there is no direct association between uric acid levels and PSP. However, a small inverse association cannot be excluded. (c) 2016 Movement Disorder Society. PMID- 26890572 TI - Establishment of the 3rd national standard for lot release testing of the Japanese encephalitis vaccine (Nakayama-NIH strain) in Korea. AB - In Korea, 2 inactivated Japanese encephalitis vaccines from Nakayama-NIH and Beijing-1 strain have been utilized to date. The 1(st) national standard for lot release testing of the JE vaccine was established in 2002. The 2(nd) national standard, established in 2007, is currently in use for JE vaccine (Nakayama-NIH strain) potency testing. However, the supply of this standard is expected to be exhausted by 2015, necessitating the establishment of a new national standard with quality equivalent to that of the existing standard. Quality control tests were performed to verify that the new standard candidate material was equivalent to that of the 2(nd) national standard, proving its appropriateness for potency testing of JE vaccine. In addition, based on the results of a collaborative study conducted among 4 institutions including Ministry of Food and Drug Safety, the potency of the new national standard material was determined to be 2.69 neutralizing-antibody titer (log10) per vial. Therefore, the newly established national standard material is expected to be used for the Japanese encephalitis vaccine lot release in Korea. PMID- 26890574 TI - Monosaccharides as Versatile Units for Water-Soluble Supramolecular Polymers. AB - We introduce monosaccharides as versatile water-soluble units to compatibilise supramolecular polymers based on the benzene-1,3,5-tricarboxamide (BTA) moiety with water. A library of monosaccharide-based BTAs is evaluated, varying the length of the alkyl chain (hexyl, octyl, decyl and dodecyl) separating the BTA and saccharide units, as well as the saccharide units (alpha-glucose, beta glucose, alpha-mannose and alpha-galactose). In all cases, the monosaccharides impart excellent water compatibility. The length of the alkyl chain is the determining factor to obtain either long, one-dimensional supramolecular polymers (dodecyl spacer), small aggregates (decyl spacer) or molecularly dissolved (octyl and hexyl) BTAs in water. For the BTAs comprising a dodecyl spacer, our results suggest that a cooperative self-assembly process is operative and that the introduction of different monosaccharides does not significantly change the self- assembly behaviour. Finally, we investigate the potential of post-assembly functionalisation of the formed supramolecular polymers by taking advantage of dynamic covalent bond formation between the monosaccharides and benzoxaboroles. We observe that the supramolecular polymers readily react with a fluorescent benzoxaborole derivative permitting imaging of these dynamic complexes by confocal fluorescence microscopy. PMID- 26890573 TI - Prescriptions, nonmedical use, and emergency department visits involving prescription stimulants. AB - OBJECTIVE: Little is known regarding the temporal trends in prescriptions, nonmedical use, and emergency department (ED) visits involving prescription stimulants in the United States. Our aim was to examine these 3 national trends involving dextroamphetamine-amphetamine and methylphenidate in adults and adolescents. METHOD: Three national surveys conducted between 2006-2011 were used: National Disease and Therapeutic Index, a survey of office-based practices; National Survey on Drug Use and Health, a population survey of substance use; and Drug Abuse Warning Network, a survey of ED visits. Ordinary least squares regression was used to examine temporal changes over time and the associations between the 3 trends. RESULTS: In adolescents, treatment visits involving dextroamphetamine-amphetamine and methylphenidate decreased over time; nonmedical dextroamphetamine-amphetamine use remained stable, while nonmedical methylphenidate use declined by 54.4% in 6 years. ED visits involving either medication remained stable. In adults, treatment visits involving dextroamphetamine-amphetamine remained unchanged, while nonmedical use went up by 67.1% and ED visits went up by 155.9%. These 3 trends involving methylphenidate remained unchanged. Across age groups, the major source for nonmedical use of both medications was a friend or relative; two-thirds of these friends and relatives had obtained the medication from a physician. CONCLUSIONS: Trends in prescriptions for stimulants do not correspond to trends in reports of nonmedical use and ED visits. Increased nonmedical stimulant use may not be simply attributed to increased prescribing trends. Future studies should focus on deeper understanding of the proportion of, risk factors for, and motivations for drug diversions. PMID- 26890575 TI - Road traffic mortality in the Slovak Republic in 1996-2014. AB - OBJECTIVE: Road traffic mortality takes an enormous toll in every society. Transport safety interventions play a crucial role in improving the situation. In the period 1996-2014 several road safety measures, including a complex new road traffic law in 2009, were implemented in the Slovak Republic, introducing stricter conditions for road users. The aim of this study is to describe and analyze the trends in road user mortality in the Slovak Republic in individual age groups by sex during the study period 1996-2014. METHODS: Data on overall mortality in the Slovak Republic for the period 1996-2014 were obtained from the Statistical Office of the Slovak Republic. Mortality rates were age-adjusted to the European standard population. Joinpoint regression was used to assess the statistical significance of change in time trends of calculated standardized mortality rates. RESULTS: Mortality rates of all types of road users as well as all age groups and both sexes in the Slovak Republic in the period 1996-2014 are decreasing. The male : female ratio decreased from 4:1 in 1996 to 2:1 in 2014. Motor vehicle users (other than motorcyclists) and pedestrians have the highest mortality rates among road user groups. Both of these groups show a significant decline in mortality rates over the study period. Within the age groups, people age 65 years and over have the highest mortality rates, followed by the age groups 25-64 and 15-24 years old. Joinpoint regression confirmed a steady, significant decline in all mortality rates over the study period. A statistically significant decrease in mortality rates in the last years of the study period was observed in the age group 25-64 and in male motorcycle users. Assessing the impact of the 2009 road traffic law, a drop was observed in the average standardized mortality rate of all road traffic users from 14.56 per 100,000 person years in the period 1996-2008 to 7.69 per 100,000 person years in the period 2009-2014. A similar drop in the average standardized mortality rate was observed in all individual road user groups. CONCLUSIONS: The implementation of the new traffic regulations may have contributed significantly to the observed decrease in mortality rates of road users in the Slovak Republic. A significant decrease in mortality was observed in all population groups and in all groups of road users. The introduction of a new comprehensive road traffic law may have expedited the decrease of road fatalities, especially in the age group 25-64 years old. This type of evidence-based epidemiology data can be used for improved targeting of future public health measures for road traffic injury prevention. PMID- 26890576 TI - Navigating the labyrinth of cardiac regeneration. AB - Heart disease is the number one cause of morbidity and mortality in the world and is a major health and economic burden, costing the United States Health Care System more than $200 billion annually. A major cause of heart disease is the massive loss or dysfunction of cardiomyocytes caused by myocardial infarctions and hypertension. Due to the limited regenerative capacity of the heart, much research has focused on better understanding the process of differentiation toward cardiomyocytes. This review will highlight what is currently known about cardiac cell specification during mammalian development, areas of controversy, cellular sources of cardiomyocytes, and current and potential uses of stem cell derived cardiomyocytes for cardiac therapies. Developmental Dynamics 245:751-761, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890578 TI - Behavioral thermoregulation in Lemur catta: The significance of sunning and huddling behaviors. AB - Regulation of body temperature poses significant problems for organisms that inhabit environments with extreme and seasonally fluctuating ambient temperatures. To help alleviate the energetic costs of autonomic responses, these organisms often thermoregulate through behavioral mechanisms. Among primates, lemurs in Madagascar experience uncharacteristically seasonal and unpredictable climates relative to other primate-rich regions. Malagasy primates are physiologically flexible, but different species use different mechanisms to influence their body temperatures. Lemur catta, the ring-tailed lemur, experiences particularly acute diurnal temperature fluctuations in its mostly open-canopy habitat in south and southwest Madagascar. Ring-tailed lemurs are also atypical among lemurs in that they appear to use both sun basking postures and huddling to maintain body temperature when ambient temperatures are cold. To our knowledge, however, no one has systematically tested whether these behaviors function in thermoregulation. We present evidence that ring-tailed lemurs use these postures as behavioral thermoregulation strategies, and that different environmental variables are associated with the use of each posture. Major predictors of sunning included ambient temperature, time of day, and season. Specifically, L. catta consistently assumed sunning postures early after daybreak when ambient temperatures were <13 degrees C, and ceased sunning around 10:00a.m., after ambient temperatures approached 26 degrees C. Sunning occurred more often during austral winter months. Huddling was associated with time of day, but not with ambient temperature or season. We conclude that L. catta tend to sun, rather than huddle, under cold weather conditions when sunning is possible. However, both sunning and huddling are important behavioral adaptations of L. catta that augment chemical thermoregulation and the absence of a dynamic, insulating pelage. Sunning and huddling help to account for the great ecological flexibility of the species, but these adaptations may be insufficient in the face of future changes in protective vegetation and temperature. Am. J. Primatol. 78:745-754, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890579 TI - An Alignment Medium for Measuring Residual Dipolar Couplings in Pure DMSO: Liquid Crystals from Graphene Oxide Grafted with Polymer Brushes. AB - Residual dipolar couplings (RDCs) have attracted attention in light of their great impact on the structural elucidation of organic molecules. However, the effectiveness of RDC measurements is limited by the shortage of alignment media compatible with widely used organic solvents, such as DMSO. Herein, we present the first liquid crystal (LC) based alignment medium that is compatible with pure DMSO, thus enabling RDC measurements of polar and intermediate polarity molecules. The liquid crystals were obtained by grafting polymer brushes onto graphene oxide (GO) using free radical polymerization. The resulting new medium offers several advantages, such as absence of background signals, narrow line shapes, and tunable alignment. Importantly, this medium is compatible with pi conjugated molecules. Moreover, sonication-induced fragmentation can reduce the size of GO sheets. The resulting anisotropic medium has moderate alignment strength, which is a prerequisite for an accurate RDC measurement. PMID- 26890577 TI - Donor brain death leads to differential immune activation in solid organs but does not accelerate ischaemia-reperfusion injury. AB - A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia-reperfusion injury (IRI) post-transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3(+) CD4(+) , CD3(+) CD8(+) T cells and NKp46(+) NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post-transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham-transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx. PMID- 26890581 TI - "Active" drops as phantom models for living cells: a mesoscopic particle-based approach. AB - Drops and biological cells share some morphological features and visco-elastic properties. The modelling of drops by mesoscopic non-atomistic models has been carried out to a high degree of success in recent years. We extend such treatment and discuss a simple, drop-like model to describe the interactions of the outer layer of cells with the surfaces of materials. Cells are treated as active mechanical objects that are able to generate adhesion forces. They appear with their true size and are made of "parcels of fluids" or beads. The beads are described by (very) few quantities/parameters related to fundamental chemical forces such as hydrophilicity and lipophilicity that represent an average of the properties of a patch of material or an area of the cell(s) surface. The investigation of adhesion dynamics, motion of individual cells, and the collective behavior of clusters of cells on materials is possible. In the simulations, the drops become active soft matter objects and different from regular droplets they do not fuse when in contact, their trajectories are not Brownian, and they can be forced "to secrete" molecules, to name some of the properties targeted by the modeling. The behavior that emerges from the simulations allows ascribing some cell properties to their mechanics, which are related to their biological features. PMID- 26890580 TI - Effects of 6-month soccer and traditional physical activity programmes on body composition, cardiometabolic risk factors, inflammatory, oxidative stress markers and cardiorespiratory fitness in obese boys. AB - Physical activity is important in obesity prevention, but the effectiveness of different physical activity modalities remains to be determined among children. The main purpose of this study was to compare the effects of a 6-month soccer programme and a traditional physical activity programme on changes in body composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status in obese boys. Eighty-eight boys (8-12 years; BMI > +2 standard deviations of WHO reference values) participated in one of three groups: soccer, traditional activity and control. Soccer and traditional activity programmes involved 3 sessions per week for 60-90 min at an average intensity of 70-80% of maximal heart rate. Control group participated in activities of normal daily living. All boys participated in school physical education, two sessions per week of 45-90-min. Measurements were taken at baseline and after 6 months, and included body size and composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status. Physical activity and dietary intake were assessed before and immediately following the intervention. The three groups had similar characteristics at baseline. After 6 months, both intervention groups had significantly lower relative fatness (% fat), waist circumference and total cholesterol, and higher cardiorespiratory fitness, self-esteem, perceived physical competence and attraction to physical activity compared with control group. In conclusion, physical activity interventions over 6 months positively influenced several indicators of health status among obese boys. The results also suggested that soccer has the potential as an effective tool for the prevention and reduction of childhood obesity and associated consequences. PMID- 26890582 TI - Editorial Comment to Should patients newly diagnosed with bladder cancer be screened for lung cancer? PMID- 26890583 TI - Possible Formation of Metastable PAH Dimers upon Pickup by Helium Droplets. AB - Using path-integral molecular dynamics simulations and two quantum-mechanical based force fields, we have investigated the conformational stability of dimers of a polycyclic aromatic hydrocarbon, perylene (C20H12), produced under typical experimental conditions of successive pick-up under helium nanodroplet environment. The most stable configurations are found to be of the stacked form with different relative orientations of the main molecular axes, perpendicular or T-shaped dimers being energetically much disfavored; however, in the presence of helium our simulations suggest that the time for rearrangement and pi-stacking may be rather long and exceed hundreds of picoseconds. In addition, highly metastable dimers that are stacked but with a helium monolayer sandwiched between the two molecules are also found as likely products upon successive pickup. This stabilization occurs owing to the stronger localization of the helium atoms facing the aromatic rings, which is further enhanced in the dimer. The implications of the present results are discussed in the perspective of possible identification by spectroscopic methods. PMID- 26890585 TI - Controlled growth of Cu-Ni nanowires and nanospheres for enhanced microwave absorption properties. AB - Copper is a good dielectric loss material but has low stability, whereas nickel is a good magnetic loss material and is corrosion resistant but with low conductivity, therefore Cu-Ni hybrid nanostructures have synergistic advantages as microwave absorption (MA) materials. Different Cu/Ni molar ratios of bimetallic nanowires (Cu13@Ni7, Cu5@Ni5 and Cu7@Ni13) and nanospheres (Cu13@Ni7, Cu5@Ni5 and Cu1@Ni3) have been successfully synthesized via facile reduction of hydrazine under similar reaction conditions, and the morphology can be easily tuned by varying the feed ratio or the complexing agent. Apart from the concentrations of Cu(2+) and Ni(2+), the reduction parameters are similar for all samples to confirm the effects of the Cu/Ni molar ratio and morphology on MA properties. Ni is incorporated into the Cu-Ni nanomaterials as a shell over the Cu core at low temperature, as proved by XRD, SEM, TEM and XPS. Through the complex relative permittivity and permeability, reflection loss was evaluated, which revealed that the MA capacity greatly depended on the Cu/Ni molar ratio and morphology. For Cu@Ni nanowires, as the molar ratio of Ni shell increased the MA properties decreased accordingly. However, for Cu@Ni nanospheres, the opposite trend was found, that is, as the molar ratio of the Ni shell increased the MA properties increased. PMID- 26890584 TI - A Feedback Model of Attention Explains the Diverse Effects of Attention on Neural Firing Rates and Receptive Field Structure. AB - Visual attention has many effects on neural responses, producing complex changes in firing rates, as well as modifying the structure and size of receptive fields, both in topological and feature space. Several existing models of attention suggest that these effects arise from selective modulation of neural inputs. However, anatomical and physiological observations suggest that attentional modulation targets higher levels of the visual system (such as V4 or MT) rather than input areas (such as V1). Here we propose a simple mechanism that explains how a top-down attentional modulation, falling on higher visual areas, can produce the observed effects of attention on neural responses. Our model requires only the existence of modulatory feedback connections between areas, and short range lateral inhibition within each area. Feedback connections redistribute the top-down modulation to lower areas, which in turn alters the inputs of other higher-area cells, including those that did not receive the initial modulation. This produces firing rate modulations and receptive field shifts. Simultaneously, short-range lateral inhibition between neighboring cells produce competitive effects that are automatically scaled to receptive field size in any given area. Our model reproduces the observed attentional effects on response rates (response gain, input gain, biased competition automatically scaled to receptive field size) and receptive field structure (shifts and resizing of receptive fields both spatially and in complex feature space), without modifying model parameters. Our model also makes the novel prediction that attentional effects on response curves should shift from response gain to contrast gain as the spatial focus of attention drifts away from the studied cell. PMID- 26890586 TI - Evaluation of estrogen in endometriosis patients: Regulation of GATA-3 in endometrial cells and effects on Th2 cytokines. AB - AIMS: Endometriosis (EM) is a hormone-dependent chronic inflammatory disease, usually accompanied by a high level of localized estrogen and abnormal levels of cytokines, which are regulated by GATA-3 in lymphocytes. This study aimed to investigate the role of estrogen on GATA-3 expression and the relationship between GATA-3 and cytokine response. METHODS: Endometrial tissues collected from 20 patients who underwent laparoscopic or open surgery were used. Immunohistochemistry, quantitative polymerase chain reaction, Western blot analysis, cell transfection, estrogen treatments and enzyme-linked immunosorbent assays were performed to evaluate the effects of estrogen on GATA-3 expression and the relationship between estrogen-induced GATA-3 and the Th2 immune status of EM. RESULTS: Estrogen regulated the expression of GATA-3 in a dose and time dependent manner. GATA-3 was relocated from the cytoplasm to the nucleus. Estrogen and GATA-3 regulated Th2 cytokine expression in eutopic endometrial cells, including interleukin (IL)-6, IL-8 and IL-10. Moreover, interferon-gamma and IL-2 were highly expressed in the GATA-3 knockdown groups. CONCLUSION: In summary, GATA-3 was induced by estrogen and may promote the occurrence and development of EM by regulating the secretion of cytokines in the eutopic endometrial cells of EM patients. PMID- 26890588 TI - Exploring work-related issues on corporate sustainability. AB - BACKGROUND: In a research project about work-related issues and corporate sustainability conducted in Brazil, the goal was to better understand how work related issues were addressed in the corporate context. Particularly, there are some specific initiatives that serve as guides to organizational decisions, which make their performance indicators for the context of corporate sustainability. OBJECTIVE: 1) To explore the presence of work-related issues and their origins in corporate sustainability approach, analyzing a) corporate disclosures; b) sustainability guidelines that are identified as relevant in corporate disclosures; c) documents that are related to sustainable development and also identified as key-documents for these guidelines and initiatives. 2) To present the activity-centered ergonomics and psychodynamics of work contributions to work related issues in a corporate sustainability approach. METHODS: An exploratory study based on multiple sources of evidence that were performed from 2012 to 2013, including interviews with companies that engaged in corporate sustainability and document analysis using the content analysis approach. RESULTS: Work-related issues have been presented since the earliest sustainable development documents. It is feasible to construct an empirical framework for work-related issues and corporate sustainability approaches. CONCLUSIONS: 1) Although some authors argue that corporate sustainability has its roots based only on the environmental dimension, there is strong empirical evidence showing that social dimension aspects such as work-related issues have been present since the beginning. 2) Some indicators should be redesigned to more precisely translate the reality of some workplaces, particularly those indicators related to organizational design and mental health. PMID- 26890589 TI - Musculoskeletal disorders and their influence on the quality of life of the dockworker: A cross-sectional study. AB - BACKGROUND: Dockworkers are subjected to intense physical labor which leads to frequent occurrence of musculoskeletal disorders. OBJECTIVE: This study aims to measure the prevalence of work-related musculoskeletal disorders (WMSD) of temporary dockworkers and its influence on their quality of life. METHODS: This was a cross-sectional study developed with temporary dockworkers in Brazil. Recruitment was done by inviting workers when they presented themselves for work at the trade union. The Nordic Musculoskeletal Questionnaire and the Short-Form Health Survey were used. The association between the outcome and the different investigated factors was analyzed through Poisson Regression with robust variance. The Mann-Whitney test was used to compare the data from the Short-Form Health Survey scale among the groups both with and without work-related musculoskeletal disorders. RESULTS: The sample was composed of 318 temporary dockworkers with a mean age of 48 years. WMSD prevalence was 37.4%. WMSD was associated with not practicing physical activity (PR = 2.03; p = 0.005), participation in housework (PR = 1.88; p = 0.029), taking care of preschool children (PR = 1.65; p < 0.000) and handling heavy objects (PR = 1.83; p = 0.007). The lumbar spine was the most frequently mentioned area of the body (22.5%) in the WMSD analysis. Workers without WMSD had higher (p < 0.00) quality of life scale scores in relation to functional capacity, physical and social aspects, pain and vitality. CONCLUSIONS: The results highlight the relevance of developing action plans regarding the needs of this specific population of workers, especially concerning the reduction of risk factors. PMID- 26890587 TI - Work-related back discomfort and associated factors among automotive maintenance mechanics in Eastern Nigeria: A cross sectional study. AB - BACKGROUND: Back pain has been identified as a common cause of disability in the working population. Automotive mechanics habitually use awkward back posture in their course of manual activity and hence may be at risk of work-related back pain. OBJECTIVE: To investigate the prevalence, pattern and severity of back pain among automotive maintenance mechanics, as well as the personal and job variables associated with or predicting occurrence of back pain. METHOD: Using a cross sectional design, information about self-reported back pain and the associated variables were collected among 684 randomly recruited automotive mechanics. RESULT: Prevalence of back pain was 76.02%; with the majority experiencing low back pain. 63.3% of the workers reported they limited their activity due to the back pain. Older workers (>50 years), daily work lasting >=5 hours duration, no more than primary education, being normal weight, frequent use of kneeling and sustained postures, and lack of knowledge of ergonomic postures were associated with increased prevalence of back pain. Lack of job autonomy, inadequate task clarity, heavy physical work load, manual material handling, strenuous posture, noisy environment, vibrations, work schedule and inadequate auxiliary support were also associated with increased prevalence of back pain among the mechanics. CONCLUSION: Work-related back pain is prevalent among automotive maintenance mechanics. Work-related back pain is high among automotive maintenance mechanics. Workstation policy and legislation on reduction of risks with combined health literacy and ergonomic education programs in this occupational group are imperative. PMID- 26890590 TI - Increased errors and decreased performance at night: A systematic review of the evidence concerning shift work and quality. AB - BACKGROUND: Shift workers have worse health outcomes than employees who work standard business hours. However, it is unclear how this poorer health shift may be related to employee work productivity. OBJECTIVE: The purpose of this systematic review is to assess the relationship between shift work and errors and performance. METHODS: Searches of MEDLINE/PubMed, EBSCOhost, and CINAHL were conducted to identify articles that examined the relationship between shift work, errors, quality, productivity, and performance. All articles were assessed for study quality. RESULTS: A total of 435 abstracts were screened with 13 meeting inclusion criteria. Eight studies were rated to be of strong, methodological quality. Nine studies demonstrated a positive relationship that night shift workers committed more errors and had decreased performance. CONCLUSIONS: Night shift workers have worse health that may contribute to errors and decreased performance in the workplace. PMID- 26890592 TI - Personal experiences of people with serious mental illness when seeking, obtaining and maintaining competitive employment in Queensland, Australia. AB - BACKGROUND: High non-participation in the labour force and unemployment remain challenging for adults with serious mental illness. OBJECTIVES: This study examined the personal experiences of people with serious mental illness when seeking, obtaining and maintaining competitive employment. The aim was to increase understanding of personal experiences of employment and how these experiences can be used to inform the assistance provided in support of clients' competitive employment goals. METHODS: Qualitative data from a two-year period were thematically analysed from one participating site in a multi-site trial of employment services integrated with public funded community mental health treatment and care. RESULTS: Both positive and negative themes arose. Positive themes included: Aspirations for a better life, receiving feedback on good job performance, employment displacing preoccupation with illness, and employment improving self-esteem and reducing financial stress. Negative themes included stigma experiences, stress, and health difficulties. Both positive and negative experiences did not depend on type of employment service assistance nor key client characteristics such as age, sex, and diagnostic category. CONCLUSIONS: Despite its many benefits, employment can also increase the risk of negative personal experiences. These findings suggest that employment service providers could do more to assist people who commence employment, to reduce the risk of negative personal experiences and to enhance the benefits of competitive employment. PMID- 26890591 TI - An examination of concepts in vocational rehabilitation that could not be linked to the ICF based on an analysis of secondary data. AB - BACKGROUND: In the last few years the International Classification of Functioning, Disability and Health (ICF) has become a widely known and useful reference classification in vocational rehabilitation. It would be equally important to know which aspects of work-related health information cannot be assigned to distinct ICF categories. OBJECTIVE: The objective of this study is to examine the concepts derived from three studies conducted within the ICF Core Set for vocational rehabilitation project, which could not be linked to distinct ICF codes in order to complement the current understanding of functioning in vocational rehabilitation. METHODS: Secondary data analysis of the concepts from the systematic literature review, expert survey and patient focus group study of the ICF Core Set for vocational rehabilitation project that were marked as nd = not definable, nc = not covered or pf = personal factor. Nd-concepts were assigned to the biopsychosocial model of the ICF; additional ICF categories were formulated where needed. Nc-concepts were grouped into common themes not covered by the ICF. Pf-categories were linked to a proposed personal factors classification. RESULTS: 1093 nd-concepts were matched to overarching terms in the ICF, and "other specified"-categories were detailed. 1924 pf-concepts were linked to 31 second level categories of a proposed personal factors classification. 441 nc-concepts were grouped into six themes including the concept of well-being and attributes related to processes and time. CONCLUSIONS: With concepts that emerged from the secondary analysis of data gathered during the vocational rehabilitation ICF Core Set project, we have enriched the ICF model with constructs specific to vocational rehabilitation. However, additional research is needed to further explore personal factors specific to vocational rehabilitation. The influence of themes complementary to the ICF such as well being and quality of life on return-to-work should be further investigated. PMID- 26890593 TI - The effect of loupes on neck pain and disability among dental hygienists. AB - BACKGROUND: Musculoskeletal disorders represent a significant occupational health issue in dental hygiene, with high prevalence rates documented. Despite this fact, there have been few advancements in the application of ergonomic principles in the dental hygiene profession. While the use of loupes is often promoted as an ergonomic solution, there is little published research to support this claim. OBJECTIVES: The aim of the present study, therefore, was to investigate the effect of the use of loupes on neck pain and disability in dental hygienists. METHODS: The study was conducted using an exploratory pre-test post-test design, comparing musculoskeletal measures in dental hygienists wearing loupes with final year dental hygiene students who do not wear loupes. Pre- and post-test measures included the Neck Pain and Disability Scale and a standardised physical assessment using previously validated measures. Statistical analysis was conducted as a series of mixed ANOVAs with time and treatment as the independent variables. RESULTS: While the analyses revealed no significant interactions between time and treatment (p < 0.05), there were general trends of improvement or deterioration for outcome measures. Improvements over time were noted in the treatment group for cervical range of motion and deep neck muscle endurance; however deteriorations were noted for forward head posture and cervical kinaesthetic sense. CONCLUSIONS: Overall, despite no statistically significant differences being detected, this study suggests that wearing loupes appears to have both positive and negative outcomes with regards to physical well-being. As such, further studies are required to more precisely determine the effects of loupes on MSD among dental hygienists, particularly long-term. Dental hygienists with existing neck pain exploring ergonomic equipment may reflect on the findings and consider the potential benefits and risks of wearing loupes. PMID- 26890594 TI - Joint health and safety committees - What is their impact in the acute care hospital? AB - BACKGROUND: There is very little in the literature on the effectiveness of Joint Health and Safety Committees (JHSCs) in the healthcare sector and a paucity of information on how JHSCs are perceived in the workplace. OBJECTIVE: This study was carried out to explore hospital worker, hospital management, and healthcare sector stakeholder views on the effectiveness of JHSCs in the acute healthcare setting. METHODS: The study used a qualitative descriptive design with: (1) nineteen focus groups and twenty two individual interviews in three hospitals of different sizes; and (2) eight individual interviews with external stakeholders. RESULTS: Study findings showed gaps in awareness and understanding of the role and responsibilities of the Joint Health and Safety Committee. Some participants indicated that JHSCs lacked profile and had low visibility in the organization. Facilitators and barriers to JHSC effectiveness were investigated and measures to assess effectiveness identified. The attributes of a "gold standard" JHSC were outlined by respondents and can be used to develop an evidence-driven assessment tool to evaluate JHSCs. CONCLUSIONS: The results of this study indicate both a continuing need for education and training related to JHSCs and the need to develop better tools to assess JHSC functioning and effectiveness. PMID- 26890595 TI - Firefighting and mental health: Experiences of repeated exposure to trauma. AB - BACKGROUND: Firefighters must be ready to respond to a broad range of emergencies every duty day. In the course of many of these emergencies, firefighters witness events which have the potential to induce emotional trauma, such as badly injured people, deceased children, and individuals who are highly distraught. Previous research suggests that repeated exposure to these traumas (RET) may have negative impacts on the emotional and mental health of fire service personnel. Research on the mental health of firefighters has been limited to small surveys reporting the prevalence of specific mental health problems such as depression and post traumatic stress disorder among firefighters. OBJECTIVE: Despite the likelihood that RET leads to negative outcomes in firefighters, data is lacking on how exposure impacts fire service personnel. The current study examines the experiences of firefighters related to RET. METHODS: Using formative research methods, we examined the beliefs and experiences of firefighters and administrators from across the United States regarding the impact of RET on firefighter health. RESULTS: Study findings highlight the cumulative psychological toll of repeated exposure to traumatic events including desensitization, flashbacks, and irritability. CONCLUSION: Results of the current study suggest that RET is a significant concern for emergency responders that warrants additional research and attention. It is likely that the long term consequences of RET are closely intertwined with other mental health outcomes and general well-being of this important occupational group. PMID- 26890596 TI - "The Florence Experience": A multimedia and multisensory guidebook for cultural towns inspired by Universal Design approach. AB - BACKGROUND: In order to plan a trip, tourists with disabilities need to gather and analyse a broad range of information concerning the features of the places and services with which they are going to interact. For these people, guidebooks may represent an important source of information for gaining prior knowledge about the various critical situations they may experience as tourists. Generally, disabled people find tourist information on dedicated communication tools; guidebooks for the disabled often provide information for wheelchair users only. OBJECTIVE: The aim of the research project was to develop a mainstream guidebook with supplementary tourist information both for people with impaired vision and for people with reduced mobility. METHODS: The communication project behind "The Florence Experience" guidebook is inspired by both the Universal Design approach and the Performance Design approach. This article describes a case study and provides suggestions for planning in similar situations. It is also part of a broader research project relating to the communication about urban spaces accessibility. RESULTS: The main outcome of the research project is a multimedia and multisensory bilingual guidebook (in Italian and English) that provides information in four separate coordinated forms: a paper-based guidebook, web pages, MP3 audio files, and portable tactile maps. CONCLUSIONS: Creating a guidebook for all is a tough challenge that requires a highly articulated vision and the cooperation of different fields of knowledge and skills. Despite the limits described in the paper, "The Florence Experience" guidebook is, in our opinion, a considerable step forward with respect to the majority of available guidebooks both because it is a unique information tool for disabled and non disabled people and because, unlike the majority of the guidebooks for disabled people, it does not only consider the needs of wheelchair users. PMID- 26890597 TI - Work family conflict in its relations to perceived working situation and work engagement. AB - BACKGROUND: These days physicians' work is characterized by an increase in economic demands, pressure and challenges in establishing a balance between work and family life. The current study investigates the relationship between physicians' job demands and resources, perceived job stress, work-family conflict, work engagement and job satisfaction. METHODS: 564 clinicians specialising in different medical fields participated in the cross-sectional study. Self-administered questionnaires, including the COPSOQ and the UWES- Scale were administered. RESULTS: Our results illustrated significant relationships between physicians' work engagement and their job satisfaction as well as between job stress and work family conflict. Moreover, perceived job stress moderated the effect of high job demands on work family conflict. In addition, significant gender differences have been found in perceived stress levels, work family conflict and work engagement. CONCLUSION: This study proves and verified associations between work engagement, work-family conflict, job demands and resources that may influence employees' satisfaction. Implications for both working physicians and hospital management are given. PMID- 26890598 TI - French good practice guidelines for management of the risk of low back pain among workers exposed to manual material handling: Hierarchical strategy of risk assessment of work situations. AB - BACKGROUND: Manual material handling remains a major cause of occupational accidents and diseases in various sectors and occupations. OBJECTIVE: This paper summarizes the main recommendations of the good practice guidelines of the French Society of Occupational Medicine for the risk assessment for back disorders in workers exposed to manual handling of loads. METHODS: The guidelines were written by a multidisciplinary working group of 24 experts, according to the Clinical Practice Guidelines method proposed by French National Health Authority, and reviewed by a multidisciplinary peer review committee of 50 experts. Recommendations were based on a large systematic review of the international literature carried out from 1990 to March 2012 and classified (Grade A, B, C or expert consensus) according to their level of evidence. RESULTS: The main recommendations are a three-level hierarchical method of risk assessment based on participatory ergonomics and suggested assessment tools that can be used routinely by professionals of occupational health, workers themselves and their supervisors. CONCLUSION: These French guidelines are intended for professionals of occupational health in charge of the prevention of low back disorders. The recommended methods are applicable to other countries than France. PMID- 26890599 TI - Effects of an expressive writing intervention on a group of public employees subjected to work relocation. AB - BACKGROUND: Pennebaker's writing technique has yielded good results on health, psychological and performance dimensions. In spite of the positive outcomes, the technique has rarely been applied directly within the workplace and its effects on burnout have never been tested. METHOD: 18 public employees subjected to work relocation were asked to write about their present work situation or another difficult event of their life (Writing Group), while another 17 were not assigned any writing task (Control Group). OBJECTIVE: To assess whether there was an improvement in burnout, alexithymia and psychological well-being in the Writing Group compared with the baseline measurement and the Control Group. RESULTS: While the baseline levels in the Writing and Control Groups in the 3 dimensions considered were similar, scores in the Writing Group at both a second (1 month after the end of the procedure) and third measurement (7 months after the end) improved when compared with the baseline, whereas those in the Control Group worsened. CONCLUSIONS: Pennebaker's writing technique appears to promote adaptive coping strategies in stressful situations, and to increase occupational and psychological well-being as well as the ability to process emotions. It also appears to buffer the negative effects of work-related stress. PMID- 26890600 TI - Guidelines for schoolbag carriage: An appraisal of safe load limits for schoolbag weight and duration of carriage. AB - BACKGROUND: There is no global agreement on a schoolbag weight limit and little assessment of its utility. The duration of carriage is another factor yet there is no previous systematic assessment of the utility of cut-off values for it in identifying schoolbag-related discomfort. OBJECTIVES: The objectives were to establish if there was a threshold for musculoskeletal discomfort based on (i) percentage bodyweight (% BW) of the schoolbag; (ii) duration of carriage; or (iii) combined % BW and duration. METHODS: Using data from 462 primary school children, a novel experimental approach was used to explore the utility of conventional schoolbag weight limit guidelines and duration of carriage. A receiver operating characteristic (ROC) curve was constructed to examine the predictive performance of schoolbag weight and duration of carriage. RESULTS: The mean schoolbag weight (4.8+/-1.43 kg) represented a mean 12.4+/-4.18% BW. Only 30.7% of the sample carried schoolbags that were <=10% BW. The majority (76%) carried schoolbags to school for <=10 minutes. No % BW, duration of carriage or mechanical burden criterion provided a threshold cut-off point for accurately predicting schoolbag-related discomfort. CONCLUSIONS: Guidelines for safe schoolbag carriage that are based on mechanical factors alone could not be upheld. The association between duration of carriage and back discomfort warrants further investigation. PMID- 26890604 TI - Notes from the Field: Administration Error Involving a Meningococcal Conjugate Vaccine--United States, March 1, 2010-September 22, 2015. AB - Menveo (GlaxoSmithKline, previously Novartis AG) is a conjugate vaccine that was recommended in October 2010 for routine use in adolescents (preferably aged 11 or 12 years, with a booster at 16 years), and among persons aged 2 through 54 years with certain immunosuppressive conditions, to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 (1). These recommendations have since been updated (2). Menveo is supplied in two vials that must be combined before administration. The MenA lyophilized (freeze-dried) component must be reconstituted with the MenCYW-135 liquid component (Figure). To administer the vaccine, the liquid component is drawn into a syringe, and used to reconstitute the lyophilized component. The resulting solution is administered by intramuscular injection. Failure to prepare Menveo as directed by the manufacturer's instructions can lead to lack of protection against the intended pathogens (N. meningitidis serogroups A, C, Y, and/or W-135) (3). Recently, an immunization provider administered only the lyophilized component of Menveo, subsequently administered a properly prepared dose of Menveo to the same patient, and asked CDC if this practice was safe. This question prompted CDC to search the Vaccine Adverse Event Reporting System (VAERS) database for reports during March 1, 2010-September 22, 2015, of only one component of Menveo being administered. Additionally, to more broadly identify disproportional reporting of adverse events in general following Menveo immunization compared with other vaccines in VAERS (including errors in vaccine preparation and administration), the Food and Drug Administration performed data mining with empiric Bayesian methods (4). PMID- 26890605 TI - Recent advances in enantioselective gold catalysis. AB - Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant pi-acids, cationic gold(i) complexes have been shown to catalyze diverse transformations of alkenes, alkynes and allenes, opening new opportunities for chemical synthesis. The development of efficient asymmetric variants is required in order to take full advantage of the preparative potential of these transformations. During the last few years, the chemical community has achieved tremendous success in the area. This review highlights the updated progress (2011-2015) in enantioselective gold catalysis. The discussion is classified according to the pi-bonds activated by gold(i), in an order of alkynes, allenes and alkenes. Other gold activation modes, such as sigma-Lewis acid catalyzed reactions and transformations of diazo compounds are also discussed. PMID- 26890606 TI - Arterial stiffness evaluated by carotid-femoral pulse wave velocity increases the risk of chronic kidney disease in a Chinese population-based cohort. AB - AIM: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. Although pulse wave velocity (PWV), which reflects arterial stiffness, was increased in subjects with CKD, little is known regarding whether arterial stiffness can increase the risk of CKD. To help clarify this we conducted a prospective cohort study to measure the association of arterial stiffness with CKD. METHODS: A total of 7154 adults aged 54.8 +/- 10.6 years undergoing physical examinations without CKD at baseline were enrolled. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cfPWV). CKD was defined as decreased estimated glomerular filtration rate (eGFR < 60 mL/min per 1.73 m2 ) or presence of proteinuria (urine protein >= 1+) assessed using a repeated dipstick method. RESULTS: During 3 years of follow-up, 167 (2.3%) patients developed CKD, 101 (1.4%) patients with proteinuria and 68 (1.0%) patients with decreased eGFR. After adjusted for potential confounders, either cfPWV (per 1 m/s increase) or the highest quartile of cfPWV (increased cfPWV) was independently associated with increased risk of proteinuria, with a fully adjusted OR of 1.15 (95% CI, 1.07 to 1.23) and 1.93 (95% CI, 1.15 to 3.25), respectively. By contrast, neither cfPWV (per 1 m/s increase) nor increased cfPWV was associated with decreased eGFR in the multivariable logistic regression analysis. CONCLUSIONS: The study revealed that arterial stiffness increases the risk of proteinuria. This suggests that vascular stiffness could be considered as a target for delaying the development of CKD. PMID- 26890603 TI - Ocimum sanctum leaf extract induces drought stress tolerance in rice. AB - Ocimum leaves are highly enriched in antioxidant components. Thus, its leaf extract, if applied in plants, is believed to efficiently scavenge ROS, thereby preventing oxidative damage under drought stress. Thus, the present study was performed in kharif 2013 and rabi 2014 season to evaluate the effect of aqueous leaf extract of Ocimum sanctum against drought stress in 2 rice genotype under glass house conditions. Here we show that various morpho- physiological (chlorophyll fluorescence, leaf rolling score, leaf tip burn, number of senesced leaves and total dry matter) and biochemical parameters (proline, malondialdehyde and superoxide dismutase content) were amended by Ocimum treatment in both the seasons. Application of Ocimum extract increased expression of dehydrin genes, while reducing expression of aquaporin genes in drought stressed rice plant. Thus, application of Ocimum leaf extract under drought stress can be suggested as a promising strategy to mitigate drought stress in economical, accessible and ecofriendly manner. PMID- 26890602 TI - AMPK activation protects cells from oxidative stress-induced senescence via autophagic flux restoration and intracellular NAD(+) elevation. AB - AMPK activation is beneficial for cellular homeostasis and senescence prevention. However, the molecular events involved in AMPK activation are not well defined. In this study, we addressed the mechanism underlying the protective effect of AMPK on oxidative stress-induced senescence. The results showed that AMPK was inactivated in senescent cells. However, pharmacological activation of AMPK by metformin and berberine significantly prevented the development of senescence and, accordingly, inhibition of AMPK by Compound C was accelerated. Importantly, AMPK activation prevented hydrogen peroxide-induced impairment of the autophagic flux in senescent cells, evidenced by the decreased p62 degradation, GFP-RFP-LC3 cancellation, and activity of lysosomal hydrolases. We also found that AMPK activation restored the NAD(+) levels in the senescent cells via a mechanism involving mostly the salvage pathway for NAD(+) synthesis. In addition, the mechanistic relationship of autophagic flux and NAD(+) synthesis and the involvement of mTOR and Sirt1 activities were assessed. In summary, our results suggest that AMPK prevents oxidative stress-induced senescence by improving autophagic flux and NAD(+) homeostasis. This study provides a new insight for exploring the mechanisms of aging, autophagy and NAD(+) homeostasis, and it is also valuable in the development of innovative strategies to combat aging. PMID- 26890607 TI - Cervical metastases of oral maxillary squamous cell carcinoma: A systematic review and meta-analysis. AB - Cervical treatment of oral maxillary squamous cell carcinoma (SCC) remains controversial. We determined the metastases incidence and evaluated its predictive factors. Systematic review and meta-analysis was conducted of 23 Chinese and English-language articles retrieved from PubMed, Ovid, Embase, Cochrane Library, China National Knowledge Infrastructure, and Chinese Scientific and Technological Journal databases. Total cervical metastases and occult metastases rate was 32% and 21%, respectively. Positive lymph node detection was likeliest from levels I to III. The maxillary gingival metastases rate was higher than that of the hard palate. Advanced-stage tumors had higher metastatic risk than early-stage tumors. Well-differentiated tumors had a significantly higher metastases rate than medium and poor-differentiation tumors. N0 cases had survival benefit compared with N+ cases. Metastases rate of oral maxillary SCC correlates significantly with T classification and pathological stage. T and N classifications impact outcome significantly. Therefore, levels I to III selective neck dissection is recommended for patients with T3/4 cN0 disease. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2335-E2342, 2016. PMID- 26890608 TI - A functional genome-wide genetic screening identifies new pathways controlling the G1/S transcriptional wave. AB - The Schizosaccharomyces pombe MBF complex activates the transcription of genes required for DNA synthesis and S phase. The MBF complex contains several proteins, including the core components Cdc10, Res1 and Res2, the co-repressor proteins Yox1 and Nrm1 and the co-activator Rep2. It has recently been shown how MBF is regulated when either the DNA damage or the DNA synthesis checkpoints are activated. However, how MBF is regulated in a normal unperturbed cell cycle is still not well understood. We have set up a genome-wide genomic screen searching for global regulators of MBF. We have crossed our knock-out collection library with a reporter strain that allows the measurement of MBF activity in live cells by flow cytometry. We confirm previously known regulators of MBF and show that COP9/signalosome and tRNA methyltransferases also regulate MBF activity. PMID- 26890610 TI - Autophagic vacuoles in cardiomyocytes of dilated cardiomyopathy with initially decompensated heart failure predict improved prognosis. AB - Autophagy is a process of bulk protein degradation and organelle turnover, and is a current therapeutic target in several diseases. The present study aimed to clarify the significance of myocardial autophagy of patients with dilated cardiomyopathy (DCM). Left ventricular endomyocardial biopsy was performed in 250 consecutive patients with DCM (54.9+/-13.9 years; male, 79%), initially presenting with decompensated heart failure (HF). The association of these findings with HF mortality or recurrence was examined. Myofilament changes, which are apparent in the degenerated cardiomyocytes of DCM, were recognized in 164 patients (66%), and autophagic vacuoles in cardiomyocytes were identified in or near the area of myofilament changes in 86 patients (34%). Morphometrically, fibrosis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.93 to 0.99) and mitochondrial abnormality (OR, 2.24; 95% CI, 1.23 to 4.08) were independently related with autophagic vacuoles. During the follow-up period of 4.9+/-3.9 y, 24 patients (10%) died, including 10 (4%) who died of HF, and 67 (27%) were readmitted for HF recurrence. Multivariate analysis identified a family history of DCM (hazard ratio [HR], 2.117; 95% CI, 1.199 to 3.738), hemoglobin level (HR, 0.845; 95% CI, 0.749 to 0.953), myofilament changes (HR, 13.525; 95% CI, 5.340 to 34.255), and autophagic vacuoles (HR, 0.214; 95% CI, 0.114 to 0.400) as independent predictors of death or readmission due to HF recurrence. In conclusion, autophagic vacuoles in cardiomyocytes are associated with a better HF prognosis in patients with DCM, suggesting autophagy may play a role in the prevention of myocardial degeneration. PMID- 26890611 TI - Course and Determinants of Anosognosia in Alzheimer's Disease: A 12-Month Follow up. AB - Anosognosia in Alzheimer's disease (AD) has been associated with greater cognitive impairment and more behavioural and psychological symptoms of dementia (BPSD). This study examines the incidence, persistence, and remission rates of anosognosia over a 12-month period, as well as the related risk factors. This was an observational 12-month prospective study. The longitudinal sample comprised 177 patients with mild or moderate AD, and their respective caregivers. Anosognosia was assessed using the Anosognosia Questionnaire in Dementia, and we also evaluated cognitive status (Mini-Mental State Examination), functional disability (Disability Assessment in Dementia), and the presence of BPSD (Neuropsychiatric Inventory). Multinomial logistic regression was used to determine the variables associated with the incidence, persistence and remission of anosognosia. The prevalence of anosognosia was 39.5% (95% CI = 32.1-47.1) at baseline. At 12 months, incidence was 38.3% (95% CI = 28.6-48.0), persistence was 80.0% (95% CI = 69.9-90.1) and remission was 20.0% (95% CI = 9.9-30.1). The regression model identified lower age, more education, and the presence of delusions as variables associated with incidence, and more education, lower instrumental DAD score, and disinhibition as variables associated with persistence. No variables were associated with remission (n = 14). The presence of anosognosia in AD patients is high. Education and certain neuropsychiatric symptoms may explain a greater and earlier incidence of anosognosia. However, anosognosia also increases with greater cognitive impairment and disease severity. PMID- 26890612 TI - Sisymbrium Officinale (L.) Scop. and its Polyphenolic Fractions Inhibit the Mutagenicity of Tert-Butylhydroperoxide in Escherichia Coli WP2uvrAR Strain. AB - One Sisymbrium officinale (L.) Scop. aqueous dry extract (SOE) and its polyphenolic fractions (Fb, Fc, Fd and Fe) were evaluated for their ability to inhibit the oxidative mutagenicity of tert-butylhydroperoxide in the Ames test. The possible involvement of desmutagenic and/or bioantimutagenic mechanisms was evaluated by applying a three-time based protocol (pre-treatment, co-treatment and post-treatment). Furthermore, some protective antioxidant mechanisms were investigated. The total polyphenol and flavonol amount was also determined, and the fingerprint was outlined by high-performance thin-layer chromatography and densitometry. SOE, Fb and Fe exhibited strong antimutagenicity against tert butylhydroperoxide in all treatment protocols, this suggesting the involvement of both desmutagenic and bioantimutagenic mechanisms. These samples also showed antioxidant properties, including neutralization of the superoxide anion, lipid peroxidation inhibition and chelation and reduction of iron. Fb and Fe were rich in polyphenols and flavonols, so suggesting a possible role of these compounds in the antimutagenicity. Taking into account that oxidative stress is responsible for the damage of various environmental toxicants, particularly tobacco smoke, present results can support the traditional use of hedge mustard by smokers to restore the vocal cord function affected by the oxidative damage and suggest a possible application of SOE and its fractions as food supplements. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890613 TI - Middle East Respiratory Syndrome Coronavirus during Pregnancy, Abu Dhabi, United Arab Emirates, 2013. AB - As of June 19, 2015, the World Health Organization had received 1,338 notifications of laboratory-confirmed infection with Middle East respiratory syndrome coronavirus (MERS-CoV). Little is known about the course of or treatment for MERS-CoV in pregnant women. We report a fatal case of MERS-CoV in a pregnant woman administered combination ribavirin-peginterferon-alpha therapy. PMID- 26890614 TI - Paul Allan Levine, M.D. (1944-2015). PMID- 26890615 TI - Decoupling Activation of Heme Biosynthesis from Anaerobic Toxicity in a Molecule Active in Staphylococcus aureus. AB - Small molecules active in the pathogenic bacterium Staphylococcus aureus are valuable tools for the study of its basic biology and pathogenesis, and many molecules may provide leads for novel therapeutics. We have previously reported a small molecule, 1, which activates endogenous heme biosynthesis in S. aureus, leading to an accumulation of intracellular heme. In addition to this novel activity, 1 also exhibits toxicity towards S. aureus growing under fermentative conditions. To determine if these activities are linked and establish what features of the molecule are required for activity, we synthesized a library of analogs around the structure of 1 and screened them for activation of heme biosynthesis and anaerobic toxicity to investigate structure-activity relationships. The results of this analysis suggest that these activities are not linked. Furthermore, we have identified the structural features that promote each activity and have established two classes of molecules: activators of heme biosynthesis and inhibitors of anaerobic growth. These molecules will serve as useful probes for their respective activities without concern for the off target effects of the parent compound. PMID- 26890617 TI - Evidence of Respiratory Syncytial Virus Spread by Aerosol. Time to Revisit Infection Control Strategies? AB - RATIONALE: Respiratory syncytial virus (RSV) is a highly contagious pathogen with a huge global health impact. It is a major cause of hospital-acquired infection; a large number of those exposed develop infection. Those infected in hospital are at increased risk of a severe clinical course. Prevention of nosocomial spread currently focuses on spread by hand and large droplets. There is little research evidence to determine if aerosol spread of infectious RSV is possible. OBJECTIVES: To determine if the air surrounding infants with RSV-positive bronchiolitis contains RSV in aerosolized particles that remain capable of causing infection. METHODS: The amount of RSV contained in aerosolized particles produced by infants with bronchiolitis due to RSV was measured using viable impactor sampling. The ability of RSV contained in these particles to infect healthy and chronic obstructive pulmonary disease (COPD) human ciliated respiratory epithelium was determined. RESULTS: We showed for the first time that infants with RSV-positive bronchiolitis nursed in a ward setting or ventilated in intensive care produced large numbers of aerosol particles containing RSV that remained infectious and were capable of infecting healthy and COPD human ciliated epithelium. A significant amount of RSV was found in particles with aerodynamic diameters less than 5 MUm. CONCLUSIONS: Many of the aerosolized particles that contained RSV in the air surrounding infants with bronchiolitis were sufficiently small to remain airborne for a significant length of time and small enough to be inhaled and deposited throughout the respiratory tract. It is likely that this leads to spread of infection to others, with dissemination of infection throughout the respiratory tract. PMID- 26890616 TI - Renal sonography in bipolar patients on long-term lithium treatment. AB - PURPOSE: The aim of the study was to analyze sonographic (US) renal findings in lithium-treated bipolar patients and to correlate them with renal function. METHODS: Renal US and renal function tests were performed on 120 patients with bipolar disorder. Ninety patients (30 males, 60 females), aged 36-82 years, had received lithium therapy for an average of 16 years, whereas 30 patients (10 males, 20 females), aged 35-85 years, who had never been exposed to lithium, served as controls. RESULTS: In the lithium-treated group, patients with macrocysts (22%) had poorer renal function with higher creatinine serum concentrations, lower estimated glomerular filtration rates, and lower urine specific gravity, compared with the patients without macrocysts. The US changes characteristic for lithium nephropathy (punctate hyperechoic foci, microcysts < 2 mm, and increased echogenicity) were seen in three patients. These patients had been treated with lithium for more than 20 years and had impaired renal function. Sixteen percent of patients in the control group had macrocysts; however, no correlation between their presence and impaired renal function was found. CONCLUSIONS: The presence of macrocysts in the kidneys of lithium-treated bipolar patients is associated with impaired renal function. The US changes characteristic for lithium nephropathy are rare, and in our study, were only found in patients treated with lithium for 20 years or more. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:354-359, 2016. PMID- 26890609 TI - What Makes a Bacterial Species Pathogenic?:Comparative Genomic Analysis of the Genus Leptospira. AB - Leptospirosis, caused by spirochetes of the genus Leptospira, is a globally widespread, neglected and emerging zoonotic disease. While whole genome analysis of individual pathogenic, intermediately pathogenic and saprophytic Leptospira species has been reported, comprehensive cross-species genomic comparison of all known species of infectious and non-infectious Leptospira, with the goal of identifying genes related to pathogenesis and mammalian host adaptation, remains a key gap in the field. Infectious Leptospira, comprised of pathogenic and intermediately pathogenic Leptospira, evolutionarily diverged from non infectious, saprophytic Leptospira, as demonstrated by the following computational biology analyses: 1) the definitive taxonomy and evolutionary relatedness among all known Leptospira species; 2) genomically-predicted metabolic reconstructions that indicate novel adaptation of infectious Leptospira to mammals, including sialic acid biosynthesis, pathogen-specific porphyrin metabolism and the first-time demonstration of cobalamin (B12) autotrophy as a bacterial virulence factor; 3) CRISPR/Cas systems demonstrated only to be present in pathogenic Leptospira, suggesting a potential mechanism for this clade's refractoriness to gene targeting; 4) finding Leptospira pathogen-specific specialized protein secretion systems; 5) novel virulence-related genes/gene families such as the Virulence Modifying (VM) (PF07598 paralogs) proteins and pathogen-specific adhesins; 6) discovery of novel, pathogen-specific protein modification and secretion mechanisms including unique lipoprotein signal peptide motifs, Sec-independent twin arginine protein secretion motifs, and the absence of certain canonical signal recognition particle proteins from all Leptospira; and 7) and demonstration of infectious Leptospira-specific signal-responsive gene expression, motility and chemotaxis systems. By identifying large scale changes in infectious (pathogenic and intermediately pathogenic) vs. non-infectious Leptospira, this work provides new insights into the evolution of a genus of bacterial pathogens. This work will be a comprehensive roadmap for understanding leptospirosis pathogenesis. More generally, it provides new insights into mechanisms by which bacterial pathogens adapt to mammalian hosts. PMID- 26890618 TI - Clinical background affecting pregnancy outcome following local endometrial injury in infertile patients with repeated implantation failure. AB - Local endometrial injury (LEI) has been performed as a promising medical intervention to improve the pregnancy outcome in infertile women suffering from repeated implantation failure (RIF) in in vitro fertilization-embryo transfer cycles. The effect of LEI, however, remains controversial. The aim of this retrospective study was to identify the subgroups of patients with RIF who benefit from LEI. We compared the clinical parameters between the patients who had had a clinical pregnancy in the subsequent embryo transfer cycle following the LEI cycle (LEI-CP group, n = 94) and those who had resulted in negative pregnancy test (LEI-NP group, n = 114). The female age, basal follicle stimulating hormone concentration, number of past oocyte pickup cycles, and embryos/blastocysts transferred in the past three RIF cycles were significantly (p < 0.047) lower in the LEI-CP group than the LEI-NP group. The prevalence of polycystic ovarian syndrome was significantly (p = 0.0059) higher in the LEI-CP group than in the LEI-NP group. These findings suggest that LEI is most effective to improve the pregnancy outcome in patients undergoing RIF with uncompromised ovarian reserve, particularly in those with polycystic ovarian syndrome. PMID- 26890620 TI - A second retrospective database analysis confirms prior findings of apparent increased cardiovascular comorbidities in hemophilia A in the United States. PMID- 26890619 TI - A Patient-Inspired Ex Vivo Liver Tissue Engineering Approach with Autologous Mesenchymal Stem Cells and Hepatogenic Serum. AB - Design and development of ex vivo bioengineered liver tissue substitutes intended for subsequent in vivo implantation has been considered therapeutically relevant to treat many liver diseases that require whole-organ replacement on a long-term basis. The present study focus on patient-inspired ex vivo liver tissue engineering strategy to generate hepatocyte-scaffold composite by combining bone marrow mesenchymal stem cells (BMSCs) derived from cardiac failure patients with secondary hyperbilirubinemia as primers of hepatic differentiation and hepatocyte growth factor (HGF)-enriched sera from same individuals as hepatic inducer. A biodegradable and implantable electrospun fibrous mesh of poly-l-lactic acid (PLLA) and gelatin is used as supporting matrix (average fiber diameter = 285 +/- 64 nm, porosity = 81 +/- 4%, and average pore size = 1.65 +/- 0.77 MUm). The fibrous mesh supports adhesion, proliferation, and hepatic commitment of patient derived BMSCs of adequate stemness using HGF-enriched sera generating metabolically competent hepatocyte-like cells, which is comparable to the hepatic induction with defined recombinant growth factor cocktail. The observed results confirm the combinatorial effects of nanofiber topography and biochemical cues in guiding hepatic specification of BMSCs. The fibrous mesh-hepatocyte construct developed in this study using natural growth factors and BMSCs of same individual is promising for future therapeutic applications in treating damaged livers. PMID- 26890621 TI - Acceptance of clinical decision support surveillance technology in the clinical pharmacy. AB - INTRODUCTION: There are clinical and economic benefits to incorporating clinical decision support systems (CDSSs) in patient care interventions in the clinical pharmacy setting. However, user dissatisfaction and resistance to HIT can prevent optimal use of such systems, particularly when users employ system workarounds and overrides. OBJECTIVES: The present study applied a modified version of the unified theory of acceptance and use of technology (UTAUT) to evaluate the disposition and satisfaction with CDSS among clinical pharmacists who perform surveillance to identify potential medication therapy interventions on patients in the hospital setting. METHODS: A survey of clinical pharmacists (N = 48) was conducted. Partial least squares (PLS) regression was used to analyze the influence of the UTAUT-related variables on behavioral intention and satisfaction with CDSS among clinical pharmacists. RESULTS: While behavioral intention did not predict actual use of HIT, facilitating conditions had a direct effect on pharmacists' use of CDSS. Likewise, satisfaction with CDSS was found to have a direct effect on use, with more satisfied users being less inclined to employ workarounds or overrides of the system. CONCLUSION: Based on the findings, organizational structures that facilitate CDSS use and user satisfaction affect the extent to which pharmacy and health care management maximize use in the clinical pharmacy setting. PMID- 26890623 TI - Laplace Approximation for Divisive Gaussian Processes for Nonstationary Regression. AB - The standard Gaussian Process regression (GP) is usually formulated under stationary hypotheses: The noise power is considered constant throughout the input space and the covariance of the prior distribution is typically modeled as depending only on the difference between input samples. These assumptions can be too restrictive and unrealistic for many real-world problems. Although nonstationarity can be achieved using specific covariance functions, they require a prior knowledge of the kind of nonstationarity, not available for most applications. In this paper we propose to use the Laplace approximation to make inference in a divisive GP model to perform nonstationary regression, including heteroscedastic noise cases. The log-concavity of the likelihood ensures a unimodal posterior and makes that the Laplace approximation converges to a unique maximum. The characteristics of the likelihood also allow to obtain accurate posterior approximations when compared to the Expectation Propagation (EP) approximations and the asymptotically exact posterior provided by a Markov Chain Monte Carlo implementation with Elliptical Slice Sampling (ESS), but at a reduced computational load with respect to both, EP and ESS. PMID- 26890622 TI - Bloodstream Infections: The peak of the iceberg. PMID- 26890624 TI - An Early-Stage Atherosclerosis Research Model Based on Microfluidics. AB - The arterial microenvironment plays a vital role in the pathology of atherosclerosis (AS). However, the interplay between the arterial microenvironment and atherogenesis remains unclear, partially due to the gap between cell culture and animal experiments. Addressing this problem, the present study reports a microfluidic AS model reconstituting early-stage AS. Physiological or AS-prone hemodynamic conditions are recapitulated on the model. The on-chip model recaptures the atherogenic responses of endothelial cells (ECs) in ways that the Petri dish could not. Significant cytotoxicity of a clinical anti-atherosclerotic drug probucol is discovered on the model, which does not appear on Petri dish but is supported by previous clinical evidence. Moreover, the anti-AS efficiency of platinum-nanoparticles (Pt-NPs) on the model shows excellent consistency with animal experiments. The early-stage AS model shows an excellent connection between Petri dish and animal experiments and highlights its promising role in bridging fundamental AS research, drug screening, and clinical trials. PMID- 26890626 TI - Encephalitis, Ontario, Canada, 2002-2013. AB - Encephalitis, a brain inflammation leading to severe illness and often death, is caused by >100 pathogens. To assess the incidence and trends of encephalitis in Ontario, Canada, we obtained data on 6,463 Ontario encephalitis hospitalizations from the hospital Discharge Abstract Database for April 2002-December 2013 and analyzed these data using multiple negative binomial regression. The estimated crude incidence of all-cause encephalitis in Ontario was ~4.3 cases/100,000 persons/year. Incidence rates for infants <1 year of age and adults >65 years were 3.9 and 3.0 times that of adults 20-44 years of age, respectively. Incidence peaks during August-September in 2002 and 2012 resulted primarily from encephalitis of unknown cause and viral encephalitis. Encephalitis occurred more frequently in older age groups and less frequently in women in Ontario when compared to England, but despite differences in population, vector-borne diseases, climate, and geography, the epidemiology was overall remarkably similar in the two regions. PMID- 26890627 TI - Reliability and Validity of a Treatment Barriers Scale for Individuals With Alcohol Use Disorder. AB - BACKGROUND: Few studies have measured addiction-specific barriers to treatment. A measurement of barriers with psychometric support that has been tested in diverse samples and that assesses multiple components of addiction treatment barriers is needed to inform providers and treatment programs. OBJECTIVES: This paper aims to provide an initial psychometric investigation of a measure of barriers to seeking addictions treatment. METHODS: Data were collected from 196 Veterans Affairs primary care patients with Alcohol Use Disorder that participated in a randomized clinical trial. RESULTS: A Principal Components Analysis revealed that the 32 item Treatment Barriers Scale (TBS) can be reduced to 14 items, measuring 4 factors: stigma, dislike of the treatment process, alcohol problem identification, and logistical concerns. Acceptable internal consistent reliability (alpha = .64-.76) and excellent precision of alpha (alpha = 0.001 0.009) was found for each subscale. Support for the measure's concurrent validity was found, for example, participants who reported more motivation to reduce their drinking perceived significantly fewer barriers to care. Support for the measure's predictive validity was also found, including that more barriers were related to future drinking among all participants and less mental health and addictions treatment visits among participants in one treatment condition. Conclusions/ Importance: Our results provide initial support for the utility of the TBS-14 among primary care patients with Alcohol Use Disorder. Use of the TBS 14 could enable healthcare providers to better understand patient-specific treatment barriers, provide corrective information on treatment misconceptions, and inform individualized treatment plans that increase patient engagement in addiction services. PMID- 26890628 TI - Estimating optimal shared-parameter dynamic regimens with application to a multistage depression clinical trial. AB - A dynamic treatment regimen consists of decision rules that recommend how to individualize treatment to patients based on available treatment and covariate history. In many scientific domains, these decision rules are shared across stages of intervention. As an illustrative example, we discuss STAR*D, a multistage randomized clinical trial for treating major depression. Estimating these shared decision rules often amounts to estimating parameters indexing the decision rules that are shared across stages. In this article, we propose a novel simultaneous estimation procedure for the shared parameters based on Q-learning. We provide an extensive simulation study to illustrate the merit of the proposed method over simple competitors, in terms of the treatment allocation matching of the procedure with the "oracle" procedure, defined as the one that makes treatment recommendations based on the true parameter values as opposed to their estimates. We also look at bias and mean squared error of the individual parameter-estimates as secondary metrics. Finally, we analyze the STAR*D data using the proposed method. PMID- 26890630 TI - WASP-ASSOCIATED FACTORS ACT IN INTERSPECIES COMPETITION DURING MULTIPARASITISM. AB - Coexistence or displacement of parasitoids in hosts during intrinsic competitive interactions between different parasitoid species (multiparasitism) may depend on their life history traits and behavior. Intense competition for possession of hosts may lead to the elimination of the inferior competitor through physical attack and/or physiological suppression. However, the mechanisms of physiological suppression during multiparasitism remain unclear. Previous work has shown that first instar larvae of the solitary endoparasitoid Meteorus pulchricornis possess well-developed mandibles that are used to kill competitors. Two gregarious endoparasitoids, Cotesia kariyai and C. rufricus, share host resources especially when the time gap of oviposition is short. Here, we investigated the physiological influence of wasp-regulatory factors of the three endoparasitoids, M. pulchricornis, C. kariyai, and C. ruficrus, in their common host Mythimna separata. We found that MpVLP alone (or with venom) deleteriously affected the development of the two gregarious species. Similarly, CkPDV plus venom had toxic effect on M. pulchricornis eggs and immature larvae, although they were not harmful to immature stages of C. ruficrus. Cotesia kariyai and C. ruficrus were able to coexist mainly through the expression of regulatory factors and both could successfully emerge from a multiparasitized host. The injection of CkPDV plus venom after oviposition in L5 host larvae facilitated C. ruficrus development and increased the rate of successful parasitism from 9% to 62%. This suggests that the two gregarious parasitoid wasps exhibit strong phylogenetic affinity, favoring their coexistence and success in multiparasitized hosts. PMID- 26890631 TI - Age-Related Changes in the Processing of Emotional Faces in a Dual-Task Paradigm. AB - Background/ Study Context: Age-related changes appear to affect the ability to identify emotional facial expressions in dual-task conditions (i.e., while simultaneously performing a second visual task). The level of interference generated by the secondary task depends on the phase of emotional processing affected by the interference and the nature of the secondary task. The aim of the present study was to investigate the effect of these variables on age-related changes in the processing of emotional faces. METHODS: The identification of emotional facial expressions (EFEs) was assessed in a dual-task paradigm using the following variables: (a) the phase during which interference was applied (encoding vs. retrieval phase); and (b) the nature of the interfering stimulus (visuospatial vs. verbal). The sample population consisted of 24 healthy aged adults (mean age = 75.38) and 40 younger adults (mean age = 26.90). The accuracy of EFE identification was calculated for all experimental conditions. RESULTS: Consistent with our hypothesis, the performance of the older group was poorer than that of the younger group in all experimental conditions. Dual-task performance was poorer when the interference occurred during the encoding phase of emotional face processing and when both tasks were of the same nature (i.e., when the experimental condition was more demanding in terms of attention). CONCLUSIONS: These results provide empirical evidence of age-related deficits in the identification of emotional facial expressions, which may be partially explained by the impairment of cognitive resources specific to this task. These findings may account for the difficulties experienced by the elderly during social interactions that require the concomitant processing of emotional and environmental information. PMID- 26890629 TI - Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection. AB - Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV-based all-oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 +/- 8.2 years; 93% had genotype 1 HCV and 31% had biopsy proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End-Stage Liver Disease (MELD) score was 13.0 +/- 6.0, and the proportion with Child-Turcotte-Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 * 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV-based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV based all-oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status. PMID- 26890632 TI - Joint Attention is Slowed in Older Adults. AB - BACKGROUND/STUDY CONTEXT: The automatic propensity to orient to the location where other people are looking is the main way of establishing joint attention with others. Whereas joint attention has been mostly investigated with young adults, the present study examines age-related differences in the magnitude and time course of joint attention. METHODS: Forty-three community-dwelling seniors and 43 younger adults performed a visuospatial task. The procedures closely follow those of gaze-cueing tasks commonly used to investigate joint attention. RESULTS: The findings revealed that a gaze-cueing effect occurs for both younger and older adults, with an equivalent average magnitude but with different time courses. The effect peaks later in older adults. CONCLUSION: Age-related differences in joint attention could be linked to a more general cognitive slowing rather than to poorer basic social skills. The present study adds to the growing interest in gerontological research regarding social attention. PMID- 26890633 TI - Predicting Value of Nine-Item Berg Balance Scale Among the Aged: A 3-Year Prospective Follow-Up Study. AB - BACKGROUND/STUDY CONTEXT: The aim was to assess the predicting value of the nine item Berg Balance Scale (BBS-9) for falls among the community-dwelling aged. METHODS: The participants (N = 298) were divided according to BBS-9 (range: 0-36) into those scoring 0-32 sum points (risk group [RG]; n = 158) and those scoring 33-36 (non-risk group [non-RG]; n = 140). Falls were recorded by fall diaries, which subjects were asked to mail to the research assistants (RAs) monthly during the 12-month follow-up. The occurrences of falls requiring treatment were collected from the health center and hospital registers during the 12- and 36 month follow-ups. RESULTS: During the 12-month follow-up, 271 falls (171 in RG and 100 in non-RG) and 29 falls requiring treatment (22 in RG and 7 in non-RG) occurred. During 36 months, there were 98 falls that required treatment (72 in RG and 26 in non-RG). The incidence of falls was higher in RG compared with non-RG (incidence rate ratio [IRR]: 1.57, 95% confidence interval [CI]: 1.23-2.01) during the 12-month follow-up (p < .001). Also, the incidence of falls requiring treatment was significantly higher in RG than in non-RG during 12 months (IRR: 2.82, 95% CI: 1.20-6.59; p = .017) and 36 months (IRR: 2.56, 95% CI: 1.63-4.01; p < .001). CONCLUSION: BBS-9 with a cutoff score of 32/33 is an applicable tool for predicting risk of falls among the community-dwelling aged. Future studies are needed to assess the predicting value of BBS-9 among different age groups in the elderly population. PMID- 26890634 TI - The Emotional Stroop as an Emotion Regulation Task. AB - BACKGROUND/STUDY CONTEXT: The present studies investigate age differences observed when performing the emotional Stroop task considered as an expression of emotion regulation. Previous studies employing this task showed mixed findings regarding age differences, with a lack of evidence for positivity effects. However, moderating factors such as arousal or dispositional (emotion) regulation strategies were mostly not taken into account. Moreover, relations between Stroop effects and emotional reactions were not examined. METHODS: In two studies (Study 1/2: nyoung = 26/41; nold = 19/39), an emotional Stroop task was employed and valence (negative, neutral, positive [Study 2 only]) and arousal of the word stimuli were varied. Additionally, flexible goal adjustment (FGA), positive and negative affect in the last 12 months, and change in momentary affect (Study 2 only) were measured. RESULTS: Study 1 showed larger emotional Stroop effects (ESE) in older than younger adults with medium arousing negative words. We also found correlations between FGA (positive correlation) as well as negative affect (negative correlation) and the ESE with medium arousing negative words. Study 2 corroborates these findings by exhibiting positive change in momentary affect with larger ESEs for medium arousing negative words in the older age group. CONCLUSIONS: The findings emphasize the importance of including arousal level and dispositional regulation measures (such as FGA) as moderating factors in age differences and within-group differences in emotion regulation. Although we did not find evidence for a positivity effect, processing in the emotional Stroop task was related to positive change in momentary affect and less negative affect in the older age group. Taken together, our experiments demonstrate that the emotional Stroop task is suited as a measure for emotion induction and related emotion regulation mechanisms. PMID- 26890635 TI - Implicit and Explicit Age Stereotypes for Specific Life Domains Across the Life Span: Distinct Patterns and Age Group Differences. AB - BACKGROUND/STUDY CONTEXT: Drawing on research that shows the importance of age stereotypes across the life span, the authors investigated domain-specific implicit and explicit age stereotypes in different age groups. METHODS: Implicit (Implicit Association Test [IAT]; Greenwald, McGhee, & Schwartz, 1998, Journal of Personality and Social Psychology, 74, 1464-1480) and explicit age stereotypes were assessed for the domains of family and health in a sample of N = 90 younger, middle-aged, and older adults. RESULTS: Overall, age stereotypes were negative for the health domain but not for the family domain. Distinct patterns of age group differences emerged depending on domain and assessment method. In the family domain, older participants held the least positive explicit age stereotypes, whereas implicit stereotypes in this domain were most positive for this age group compared with the young and middle-aged groups. For the health domain, implicit and explicit age associations indicated that middle-aged participants showed the most negative age-associations. CONCLUSIONS: These findings suggest that implicit and explicit age stereotypes in different life domains represent largely independent constructs. Differential age group effects are assumed to reflect the result of accommodative and assimilative processes that are used to cope with age-related changes. Implications for future studies of implicit and explicit age stereotypes and their influence on developmental regulation are discussed. PMID- 26890636 TI - Aging and Self-Discrepancy: Evidence for Adaptive Change Across the Life Span. AB - BACKGROUND/STUDY CONTEXT: Higgins' self-discrepancy theory (SDT; Higgins, 1987, Psychological Review, 94, 319-340) postulates that individuals are motivated to decrease the discrepancy between their current and future selves. The objective of the current research was to investigate adult age differences in quantitative and qualitative aspects of self-discrepancy. METHODS: Higgins' self-guide strength measure (Higgins et al., 1997, Journal of Personality and Social Psychology, 72, 515-525) was utilized to compare self-discrepancy in older (aged 65-84) and younger (aged 17-30) healthy, community-dwelling adults. Additionally, the possible selves generated in the task were analyzed thematically. RESULTS: Age was associated with lowered expectations concerning both current and future selves, but the magnitude of self-discrepancy remained constant across the life span. Thematically, interpersonal-related possible selves were important for both age groups, whereas significant age differences emerged in several other thematic domains: younger adults generated significantly more related to achievement, whereas older adults were significantly more concerned with duties, obligations, and health. DISCUSSION: These findings reflect adaptive age-related changes in expectations and motivational priorities in line with life span theories of development. PMID- 26890637 TI - Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies. AB - PURPOSE: (S)-4-(3-[18F]Fluoropropyl)-L-glutamic acid (18F-FSPG) is a novel radiopharmaceutical for Positron Emission Tomography (PET) imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies. EXPERIMENTAL DESIGN: For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years). After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT) scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers. RESULTS: In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7). 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model. CONCLUSIONS: 18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned. TRIAL REGISTRATION: ClinicalTrials.gov NCT01186601. PMID- 26890639 TI - "A test of core psychopathic traits as a moderator of the efficacy of a brief motivational intervention for substance-using offenders": Correction to Swogger et al. (2016). AB - Reports an error in "A Test of Core Psychopathic Traits as a Moderator of the Efficacy of a Brief Motivational Intervention for Substance-Using Offenders" by Marc T. Swogger, Kenneth R. Conner, Eric D. Caine, Nicole Trabold, Melissa N. Parkhurst, Laurel M. Prothero and Stephen A. Maisto (Journal of Consulting and Clinical Psychology, Advanced Online Publication, Jan 4, 2016, np). The sentence in the 1st paragraph of the Intervention and Control Conditions section, "Over the course of the study, individuals in the intervention condition averaged 3.8 (SD 0.40) sessions." It should read, "2.5 (SD 1.1) sessions." (The following abstract of the original article appeared in record 2015-58971-001.) OBJECTIVE: In a randomized controlled trial we studied a brief motivational intervention (BMI) for substance use, examining core psychopathic traits as a moderator of treatment efficacy. METHOD: Participants were 105 males and females who were 18 years of age and older and in a pretrial jail diversion program. The sample was approximately 52% Black and other minorities and 48% White. Outcome variables at a 6-month follow-up were frequency of substance use (assessed with the Timeline Follow-back Interview and objective toxicology screens), substance use consequences (Short Inventory of Problems-Alcohol and Drug version), and self reported participation in nonstudy mental health and/or substance use treatment. Psychopathy was assessed using the Psychopathy Checklist-Revised (PCL-R). RESULTS: BMI interacted with core psychopathic traits to account for 7% of the variance in substance use at follow-up. Treatment was associated with greater use among individuals with high levels of core psychopathic traits. Toxicology screening results were consistent with self-report data. The treatment and standard care groups did not differ on substance use consequences or nonstudy treatment participation at follow-up, and no moderation was found with these outcomes. An exploratory analysis indicated that low levels of affective traits of psychopathy were associated with benefit from the BMI in terms of decreased substance use. DISCUSSION: Findings suggest that caution is warranted when applying BMIs among offenders; individuals with high levels of core psychopathic traits may not benefit and may be (PsycINFO Database Record). PMID- 26890640 TI - Automatic Segmentation of Wrist Bones in CT Using a Statistical Wrist Shape + Pose Model. AB - Segmentation of the wrist bones in CT images has been frequently used in different clinical applications including arthritis evaluation, bone age assessment and image-guided interventions. The major challenges include non uniformity and spongy textures of the bone tissue as well as narrow inter-bone spaces. In this work, we propose an automatic wrist bone segmentation technique for CT images based on a statistical model that captures the shape and pose variations of the wrist joint across 60 example wrists at nine different wrist positions. To establish the correspondences across the training shapes at neutral positions, the wrist bone surfaces are jointly aligned using a group-wise registration framework based on a Gaussian Mixture Model. Principal component analysis is then used to determine the major modes of shape variations. The variations in poses not only across the population but also across different wrist positions are incorporated in two pose models. An intra-subject pose model is developed by utilizing the similarity transforms at all wrist positions across the population. Further, an inter-subject pose model is used to model the pose variations across different wrist positions. For segmentation of the wrist bones in CT images, the developed model is registered to the edge point cloud extracted from the CT volume through an expectation maximization based probabilistic approach. Residual registration errors are corrected by application of a non rigid registration technique. We validate the proposed segmentation method by registering the wrist model to a total of 66 unseen CT volumes of average voxel size of 0.38 mm. We report a mean surface distance error of 0.33 mm and a mean Jaccard index of 0.86. PMID- 26890641 TI - Real-Time Visualization of Tissue Surface Biochemical Features Derived From Fluorescence Lifetime Measurements. AB - Fiber based fluorescence lifetime imaging has shown great potential for intraoperative diagnosis and guidance of surgical procedures. Here we describe a novel method addressing a significant challenge for the practical implementation of this technique, i.e., the real-time display of the quantified biochemical or functional tissue properties superimposed on the interrogated area. Specifically, an aiming beam (450 nm) generated by a continuous-wave laser beam was merged with the pulsed fluorescence excitation light in a single delivery/collection fiber and then imaged and segmented using a color-based algorithm. We demonstrate that this approach enables continuous delineation of the interrogated location and dynamic augmentation of the acquired frames with the corresponding fluorescence decay parameters. The method was evaluated on a fluorescence phantom and fresh tissue samples. Current results demonstrate that 34 frames per second can be achieved for augmenting videos of 640 * 512 pixels resolution. Also we show that the spatial resolution of the fluorescence lifetime map depends on the tissue optical properties, the scanning speed, and the frame rate. The dice similarity coefficient between the fluorescence phantom and the reconstructed maps was estimated to be as high as 93%. The reported method could become a valuable tool for augmenting the surgeon's field of view with diagnostic information derived from the analysis of fluorescence lifetime data in real-time using handheld, automated, or endoscopic scanning systems. Current method provides also a means for maintaining the tissue light exposure within safety limits. This study provides a framework for using an aiming beam with other point spectroscopy applications. PMID- 26890638 TI - T47D Cells Expressing Myeloperoxidase Are Able to Process, Traffic and Store the Mature Protein in Lysosomes: Studies in T47D Cells Reveal a Role for Cys319 in MPO Biosynthesis that Precedes Its Known Role in Inter-Molecular Disulfide Bond Formation. AB - Among the human heme-peroxidase family, myeloperoxidase (MPO) has a unique disulfide-linked oligomeric structure resulting from multi-step processing of the pro-protein monomer (proMPO) after it exits the endoplasmic reticulum (ER). Related family members undergo some, but not all, of the processing steps involved with formation of mature MPO. Lactoperoxidase has its pro-domain proteolytically removed and is a monomer in its mature form. Eosinophil peroxidase undergoes proteolytic removal of its pro-domain followed by proteolytic separation into heavy and light chains and is a heterodimer. However, only MPO undergoes both these proteolytic modifications and then is further oligomerized into a heterotetramer by a single inter-molecular disulfide bond. The details of how and where the post-ER processing steps of MPO occur are incompletely understood. We report here that T47D breast cancer cells stably transfected with an MPO expression plasmid are able to efficiently replicate all of the processing steps that lead to formation of the mature MPO heterotetramer. MPO also traffics to the lysosome granules of T47D cells where it accumulates, allowing in-depth immunofluorescent microscopy studies of MPO trafficking and storage for the first time. Using this novel cell model we show that formation of MPO's single inter-molecular disulfide bond can occur normally in the absence of the proteolytic events that lead to separation of the MPO heavy and light chains. We further demonstrate that Cys319, which forms MPO's unique inter-molecular disulfide bond, is important for events that precede this step. Mutation of this residue alters the glycosylation and catalytic activity of MPO and blocks its entry into the endocytic pathway where proteolytic processing and disulfide bonding occur. Finally, using the endocytic trafficking of lysosomal hydrolases as a guide, we investigate the role of candidate receptors in the endocytic trafficking of MPO. PMID- 26890642 TI - Spatial Angular Compounding of Photoacoustic Images. AB - Photoacoustic (PA) images utilize pulsed lasers and ultrasound transducers to visualize targets with higher optical absorption than the surrounding medium. However, they are susceptible to acoustic clutter and background noise artifacts that obfuscate biomedical structures of interest. We investigated three spatial angular compounding methods to improve PA image quality for biomedical applications, implemented by combining multiple images acquired as an ultrasound probe was rotated about the elevational axis with the laser beam and target fixed. Compounding with conventional averaging was based on the pose information of each PA image, while compounding with weighted and selective averaging utilized both the pose and image content information. Weighted-average compounding enhanced PA images with the least distortion of signal size, particularly when there were large (i.e., 2.5 mm and 7 ( degrees )) perturbations from the initial probe position. Selective-average compounding offered the best improvement in image quality with up 181, 1665, and 1568 times higher contrast, CNR, and SNR, respectively, compared to the mean values of individual PA images. The three presented spatial compounding methods have promising potential to enhance image quality in multiple photoacoustic applications. PMID- 26890643 TI - Improvements in RF Shimming in High Field MRI Using High Permittivity Materials With Low Order Pre-Fractal Geometries. AB - Ultra-high field MRI is an area of great interest for clinical research and basic science due to the increased signal-to-noise, spatial resolution and magnetic susceptibility-based contrast. However, the fact that the electromagnetic wavelength in tissue is comparable to the relevant body dimensions means that the uniformity of the excitation field is much poorer than at lower field strengths. In addition to techniques such as transmit arrays, one simple but effective method to counteract this effect is to use high permittivity "pads". Very high permittivities enable thinner, flexible pads to be used, but the limiting factor is wavelength effects within the pads themselves, which can lead to image artifacts. So far, all studies have used simple continuous rectangular/circular pad geometries. In this work we investigate how the wavelength effects can be partially mitigated utilizing shaped pad with holes. Several arrangements have been simulated, including low order pre-fractal geometries, which maintain the overall coverage of the pad, but can provide better image homogeneity in the region of interest or higher sensitivity depending on the setup. Experimental data in the form of in vivo human images at 7T were acquired to validate the simulation results. PMID- 26890644 TI - Accidental Dural Puncture and Postdural Puncture Headache: What Are Our Options? PMID- 26890645 TI - Direct Oral Anticoagulants: Correlation of Laboratory Monitoring With Safe Interventional Pain Procedures. PMID- 26890646 TI - Vigilance to Medical Device Failures. PMID- 26890647 TI - Unintended Impact of New Guidelines for Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications. PMID- 26890648 TI - Reply to Drs Guffey and Fingerman. PMID- 26890649 TI - The Ultrasound-Guided Retroclavicular Block: Comparison With a Novel Subpectoral Approach. PMID- 26890650 TI - Reply to Dr Vaghadia and Colleagues. PMID- 26890651 TI - Dueling Guidelines. PMID- 26890652 TI - Reply to Dr Norris. PMID- 26890653 TI - Redirecting Efforts to Achieve Patient Satisfaction in the Chronic Pain Clinic. PMID- 26890654 TI - Application of and Choice of Nerves Determine the Success of Regional Anesthesia at the Ankle. PMID- 26890655 TI - Tuberculous meningitis: a diagnostic challenge and a devastating outcome. PMID- 26890657 TI - Hybrid feedback feedforward: An efficient design of adaptive neural network control. AB - This paper presents an efficient hybrid feedback feedforward (HFF) adaptive approximation-based control (AAC) strategy for a class of uncertain Euler Lagrange systems. The control structure includes a proportional-derivative (PD) control term in the feedback loop and a radial-basis-function (RBF) neural network (NN) in the feedforward loop, which mimics the human motor learning control mechanism. At the presence of discontinuous friction, a sigmoid-jump function NN is incorporated to improve control performance. The major difference of the proposed HFF-AAC design from the traditional feedback AAC (FB-AAC) design is that only desired outputs, rather than both tracking errors and desired outputs, are applied as RBF-NN inputs. Yet, such a slight modification leads to several attractive properties of HFF-AAC, including the convenient choice of an approximation domain, the decrease of the number of RBF-NN inputs, and semiglobal practical asymptotic stability dominated by control gains. Compared with previous HFF-AAC approaches, the proposed approach possesses the following two distinctive features: (i) all above attractive properties are achieved by a much simpler control scheme; (ii) the bounds of plant uncertainties are not required to be known. Consequently, the proposed approach guarantees a minimum configuration of the control structure and a minimum requirement of plant knowledge for the AAC design, which leads to a sharp decrease of implementation cost in terms of hardware selection, algorithm realization and system debugging. Simulation results have demonstrated that the proposed HFF-AAC can perform as good as or even better than the traditional FB-AAC under much simpler control synthesis and much lower computational cost. PMID- 26890658 TI - Measuring the Thickness and Potential Profiles of the Space-Charge Layer at Organic/Organic Interfaces under Illumination and in the Dark by Scanning Kelvin Probe Microscopy. AB - Scanning Kelvin probe microscopy was used to measure band-bending at the model donor/acceptor heterojunction poly(3-hexylthiophene) (P3HT)/fullerene (C60). Specifically, we measured the variation in the surface potential of C60 films with increasing thicknesses grown on P3HT to produce a surface potential profile normal to the substrate both in the dark and under illumination. The results confirm a space-charge carrier region with a thickness of 10 nm, consistent with previous observations. We discuss the possibility that the domain size in bulk heterojunction organic solar cells, which is comparable to the space-charge layer thickness, is actually partly responsible for less than expected electron/hole recombination rates. PMID- 26890659 TI - Characterization of Ocular Biomechanics in Pellucid Marginal Degeneration. AB - PURPOSE: This study sought to investigate the diagnostic capacity of corneal biomechanical response parameters in a group of patients with pellucid marginal degeneration (PMD) using the Ocular Response Analyzer (ORA) and Corvis ST devices. METHODS: In this prospective clinical study, we used the Corvis ST and ORA devices to investigate the ocular biomechanics of patients with PMD. Eighty one eyes were included, and 2 study groups were formed: the PMD group (the study group, n = 29) and the control group (n = 52). We focused on 13 biomechanical parameters. Statistical analysis was performed using SPSS. Biomechanical parameters for the 2 groups were compared using analysis of covariance. RESULTS: The ORA results demonstrated that the Keratoconus Match Index was significantly lower in the PMD group than in the control group (0.031 +/- 0.37 vs. 0.79 +/- 0.33; P = 0.001). The 2 groups did not significantly differ with respect to intraocular pressure- and central corneal thickness-adjusted values for corneal hysteresis or corneal resistance factor. Regarding the Corvis parameters, differences between the control and PMD groups were detected for CorWmax amp (control 1.01 +/- 0.01, PMD 1.06 +/- 0.01; P = 0.020) and CorA2 t (control 21.78 +/- 0.03, PMD 21.66 +/- 0.04; P = 0.0003). CONCLUSIONS: We identified 2 Corvis parameters that could be used to characterize PMD and differentiate PMD corneas from normal corneas. These parameters support the hypothesis that there is significantly less deformation of the central cornea in PMD corneas than in healthy corneas. However, because useful "first-line" diagnostic devices for diagnosing PMD (such as Pentacam and the ORA) exist, the Corvis ST serves as an additional diagnostic tool that can also be used for long-term monitoring after diagnosis confirmation. PMID- 26890660 TI - Manual Provocation Test for Intermittent Involutional Entropion. AB - PURPOSE: To describe the manual provocation test (MPT), a novel test for intermittent involutional entropion of the lower eyelid. METHODS: Retrospective review of patients with intermittent entropion who presented with ocular irritation and documented inward eyelid rotation by them or their referring physicians, but who had no apparent entropion at the time of initial consultation. Results of the MPT were recorded for this group, and then evaluated prospectively in an age-matched comparison group of patients presenting for blepharoplasty who had no history of entropion. The essential steps of the MPT are as follows. Step 1: the lower eyelid skin is grasped below the inferior border of the tarsal plate. Step 2: the lid is drawn anteriorly as with the eyelid distraction test. Step 3: the patient is directed to forcefully close the eyelids. Step 4: the eyelid is released and the result is observed for manifest entropion. RESULTS: Thirteen eyelids in 12 patients with intermittent involutional lower eyelid entropion were included in this study. Average patient age was 77.3 years (+/-9.5 SD). The MPT elicited entropion in all 13 eyelids. Of the 12 patients, 9 elected to pursue surgery and, of these patients, all eyelids were successfully treated with subsequent improvement of symptoms. The MPT was thereafter negative in these patients. None of the 20 patients in the blepharoplasty comparison group (average age 71.6 years) demonstrated a positive MPT. CONCLUSIONS: The MPT can be a valuable and straightforward test in the clinical evaluation of patients with a history of intermittent entropion. PMID- 26890661 TI - Corneal Sensitivity and Presence of Pathogenic Organisms Among Participants Who Have Undergone Trichiasis Surgery Differ by Surgical Outcome. AB - PURPOSE: To explore the potential association between reduced corneal sensation and/or conjunctival bacterial colonization and postoperative trichiasis and eyelid contour abnormalities after corrective eyelid surgery among participants with a history of trachomatous trichiasis. METHODS: As an ancillary study to the Partnership for Rapid Elimination of Trachoma (PRET) Surgery Trial in southern Tanzania, we collected data on 580 PRET participants who had undergone trichiasis surgery 1 year earlier and 200 age-group-matched individuals without trichiasis. Assessments included eyelid status evaluation (presence and severity of postoperative trichiasis and/or eyelid contour abnormality), corneal sensitivity by Cochet-Bonnet aesthesiometer, a questionnaire on symptoms of ocular irritation, and conjunctival microbiology. We divided PRET participants based on their eyelid status and compared results across PRET groups and versus normals. RESULTS: PRET participants had reduced corneal sensitivity compared with age matched normals (mean sensitivity ranged from 2.8 to 3.8 cm in PRET participants vs. 5.9 cm in normals), and increasing severity of postoperative trichiasis was associated in a stepwise fashion with reduced corneal sensitivity (mean = 3.5 cm for mild and 2.6 cm for severe postoperative trichiasis). Conjunctival colonization with pathogenic bacteria was also associated with more severe postoperative trichiasis (Cochran-Armitage trend test P = 0.001) and with reduced corneal sensitivity (trend test P < 0.0001). Symptoms of ocular irritation were not associated with previous trichiasis surgery, postoperative trichiasis, or eyelid contour abnormality. CONCLUSIONS: These findings indicate that reduced corneal sensitivity accompanies trachomatous trichiasis and suggest that reduced corneal sensitivity may play an important role in the harboring of pathogenic bacteria on the ocular surface. PMID- 26890656 TI - Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus. AB - Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression. PMID- 26890662 TI - Comparison of Moderate- to High-Astigmatism Corrections Using WaveFront-Guided Laser In Situ Keratomileusis and Small-Incision Lenticule Extraction. AB - PURPOSE: To evaluate and compare refractive outcomes of moderate- and high astigmatism correction after wavefront-guided laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). METHODS: This comparative study enrolled a total of 64 eyes that had undergone SMILE (42 eyes) and wavefront-guided LASIK (22 eyes). Preoperative cylindrical diopters were <= 2.25 D in moderate- and >-2.25 D in high-astigmatism subgroups. The refractive results were analyzed based on the Alpins vector method that included target induced astigmatism, surgically induced astigmatism, difference vector, correction index, index of success, magnitude of error, angle of error, and flattening index. All subjects completed the 3-month follow-up. RESULTS: No significant differences were found in the target-induced astigmatism, surgically induced astigmatism, and difference vector between SMILE and wavefront-guided LASIK. However, the average angle of error value was -1.00 +/- 3.16 after wavefront-guided LASIK and 1.22 +/- 3.85 after SMILE with statistical significance (P < 0.05). The absolute angle of error value was statistically correlated with difference vector and index of success after both procedures. In the moderate-astigmatism group, correction index was 1.04 +/- 0.15 after wavefront-guided LASIK and 0.88 +/- 0.15 after SMILE (P < 0.05). However, in the high-astigmatism group, correction index was 0.87 +/- 0.13 after wavefront-guided LASIK and 0.88 +/- 0.12 after SMILE (P = 0.889). CONCLUSIONS: Both procedures showed preferable outcomes in the correction of moderate and high astigmatism. However, high astigmatism was undercorrected after both procedures. Axial error of astigmatic correction may be one of the potential factors for the undercorrection. PMID- 26890663 TI - Surgery Versus Interferon Alpha-2b Treatment Strategies for Ocular Surface Squamous Neoplasia: A Literature-Based Decision Analysis. AB - PURPOSE: To compare treatment strategies for ocular surface squamous neoplasia (OSSN), ranging from surgical excision to empiric topical interferon alpha-2b (IFN-alpha2b). METHODS: A decision model was constructed to determine which of 4 treatment strategies minimized expected persistence/recurrence of disease in patients with OSSN: excision followed by repeat excision for positive surgical margins, excision followed by IFN-alpha2b for positive margins, incisional biopsy followed by IFN-alpha2b for positive biopsies, and empiric treatment with IFN alpha2b. Probabilities were estimated from literature published between 1983 and 2015. Expected values for the probability of recurrence could range from 0 (no persistence/recurrence) to 1 (persistence/recurrence). Sensitivity analyses were performed for each variable. RESULTS: Excision followed by IFN-alpha2b for positive margins was estimated to minimize persistence/recurrence of OSSN (expected value 0.13 versus 0.17 for empiric IFN-alpha2b, 0.22 for excision-only, and 0.30 for incisional biopsy-directed IFN-alpha2b). The optimal strategy was sensitive to 3 variables: efficacy of IFN-alpha2b, recurrence after negative surgical margins, and accuracy of excisional biopsy. CONCLUSIONS: In our decision analysis using studies published between 1983 and 2015, surgical excision followed by IFN-alpha2b for positive margins is the favored strategy for minimizing persistence/recurrence of OSSN. Future prospective studies would add to the certainty of these conclusions. PMID- 26890664 TI - Impact of Eyelid Laxity on Symptoms and Signs of Dry Eye Disease. AB - PURPOSE: To study the relationship between eyelid laxity and ocular symptoms and signs of dry eye (DE). METHODS: A total of 138 patients with normal external anatomy were prospectively recruited from a Veterans Administration hospital. Symptoms (via the Dry Eye Questionnaire 5 and Ocular Surface Disease Index) and signs of DE were assessed along with presence or absence of eyelid laxity. RESULTS: It was observed that 71% of participants (n = 98) had clinical evidence of eyelid laxity (upper and/or lower) compared with 29% (n = 40) with no eyelid laxity. Individuals with eyelid laxity were older (67 +/- 10 vs. 55 +/- 8 years without laxity, P < 0.005) and more frequently male (76% of males had laxity vs. 18% females, P < 0.005). Patients with eyelid laxity had increased symptoms and signs of DE compared with their counterparts without laxity including ocular pain described as grittiness (63% vs. 45%, P = 0.049), decreased tear break-up time (8.6 +/- 3 vs. 10.3 +/- 4 seconds, P = 0.02), increased corneal staining (2.5 +/- 3 vs. 1 +/- 2, P = 0.002), decreased Schirmer score (14+/-6 vs. 17+/-7 mm, P = 0.01), increased meibomian gland drop out (2 +/- 1 vs. 0.8 +/- 0.8, P < 0.005), increased eyelid vascularity (0.8 +/- 0.8 vs. 0.2 +/- 0.5, P < 0.005), and more abnormal meibum quality (2 +/- 1.3 vs. 1.4 +/- 1.2, P = 0.02). In a multivariable analysis considering both signs of DE and laxity, lower eyelid laxity remained significantly associated with ocular surface disease index scores, suggesting a direct effect of laxity on symptoms of DE. CONCLUSIONS: The presence of eyelid laxity associates with abnormal tear parameters compared with the absence of eyelid laxity. Based on these data, it is important for clinicians to test for eyelid laxity in patients with symptoms and/or signs of DE. PMID- 26890665 TI - Candida Interface Infections After Descemet Stripping Automated Endothelial Keratoplasty. AB - PURPOSE: To describe 2 Candida interface keratitis infections occurring in the setting of positive donor rim cultures from precut corneal tissue used for Descemet stripping automated endothelial keratoplasty (DSAEK) and the ensuing public health investigation. METHODS: Following 2 clinical Candida interface keratitis infections, patients from 2012 to 2014 in the same surgical center were evaluated for bacterial and fungal rim cultures and subsequent infection. All cases of fungal infections occurring post-DSAEK were analyzed. Data included patient demographics, surgical technique, donor rim cultures, donor mate outcomes, clinical courses, and outcomes. A review of the relevant literature was also undertaken. RESULTS: From 2012 to 2014, among 99 DSAEK procedures performed, 7 (7.1%) donor rim cultures were positive for fungi. Use of this tissue with positive donor rim cultures resulted in 2 (28.6%) episodes of confirmed fungal interface keratitis, both Candida species, and presumptive treatment in an additional 2 patients. An investigation did not identify any breach in sterile technique or procedures by the surgeon or surgery center. Our literature review identified 15 reports of postoperative fungal infection associated with DSAEK, of which 11 involved Candida spp. CONCLUSIONS: While postoperative infection remains rare, our 2 additional cases along with those previously reported suggest that DSAEK may be susceptible to infection with Candida spp. Furthermore, this report of correlated rim cultures and clinical infection suggests a need for reevaluation of the utility of obtaining routine corneoscleral donor rim fungal culture. PMID- 26890666 TI - "Salt and Pepper Endothelium" Recurring After Descemet Membrane Endothelial Keratoplasty. AB - PURPOSE: To describe the presence of "salt and pepper endothelium", that is, typical cellular inclusion bodies in a patient with Fuchs endothelial corneal dystrophy (FECD), that recurred in the donor corneal endothelial cells after Descemet membrane endothelial keratoplasty (DMEK). METHODS: A 76-year-old man underwent DMEK for FECD in his left eye. Routine specular microscopy imaging, best-corrected visual acuity measurements, and pachymetry measurements were performed before and after surgery. RESULTS: Besides large guttae indicating FECD, preoperative specular microscopy images showed variable-sized dark cellular inclusion bodies in the endothelial cells. One month after DMEK, donor endothelial cells appeared normal; however, at 3 months, the typical inclusion bodies reappeared and progressed slowly within a 4-year follow-up period. Both best-corrected visual acuity and pachymetry were stable throughout the study period. CONCLUSIONS: "Salt and pepper endothelium" recurred after the host tissue was exchanged by donor Descemet membrane, that is, a DMEK graft. These changes may indicate that either the donor corneal endothelial cell morphology is modified by adjacent tissue structures or that it is completely replaced by recipient endothelium within the first months after surgery. PMID- 26890667 TI - Deep Laser-Assisted Lamellar Anterior Keratoplasty With Microkeratome-Cut Grafts. AB - PURPOSE: The goals of this laboratory study were to evaluate the interface quality in laser-assisted lamellar anterior keratoplasty (LALAK) with microkeratome-cut grafts and achieve good graft-host apposition. METHODS: Simulated LALAK surgeries were performed on 6 pairs of eye-bank corneoscleral discs. Anterior lamellar grafts were precut with microkeratomes. Deep femtosecond (FS) laser cuts were performed on host corneas followed by excimer laser smoothing. Different parameters of FS laser cuts and excimer laser smoothing were tested. Optical coherence tomography was used to measure corneal pachymetry and evaluate graft-host apposition. The interface quality was quantified in a masked fashion using a 5-point scale based on scanning electron microscopy images. RESULTS: Deep FS laser cuts at 226 to 380 MUm resulted in visible ridges on the host bed. Excimer laser smoothing with a central ablation depth of 29 MUm and saline as a smoothing agent did not adequately reduce ridges (score = 4.0). Deeper excimer laser ablation of 58 MUm and Optisol-GS as a smoothing agent smoothed ridges to an acceptable level (score = 2.1). Same sizing of the graft and host cut diameters with an approximately 50-MUm deeper host side cut relative to the central graft thickness provided the best graft-host fit. CONCLUSIONS: Deep excimer laser ablation with a viscous smoothing agent was needed to remove ridges after deep FS lamellar cuts. The host side cut should be deep enough to accommodate thicker graft peripheral thickness compared with the center. This LALAK design provides smooth lamellar interfaces, moderately thick grafts, and good graft-host fits. PMID- 26890668 TI - Restoration of Fornix Tear Reservoir in Conjunctivochalasis With Fornix Reconstruction. AB - PURPOSE: To determine whether conjunctivochalasis (CCh) obliterates the fornix tear reservoir and to discern whether there is concomitant aqueous tear deficiency (ATD) dry eye. METHODS: Retrospective review of 18 eyes of 12 patients with CCh and ATD (CCh + ATD) and 18 eyes of 13 patients with CCh without ATD (CCh - ATD). Changes were compared before and after fornix reconstruction regarding symptoms, basal tear volumes, use of medications, conjunctival inflammation, and corneal staining. RESULTS: Fornix reconstruction with conjunctival recession and amniotic membrane transplantation effectively restored the fornix tear reservoir as evidenced by a significant increase of the basal tear volume in both CCh - ATD and CCh + ATD groups. Multivariate regression analysis confirmed that such improvement was significantly correlated with symptomatic resolution (r = 1, P < 0.001), which was also accompanied by significant resolution of corneal staining, conjunctival inflammation, and reduction of topical medications. Intriguingly, the prior diagnosis of ATD was no longer existent in 10 of the 18 eyes (56%) with CCh + ATD suggesting that ATD could be secondary to obliteration of the fornix tear reservoir by CCh. CONCLUSIONS: Obliteration of the fornix tear reservoir is a common pathogenic process regardless of whether CCh is associated with ATD dry eye. Restoration of the tear reservoir by fornix reconstruction with conjunctival recession and amniotic membrane transplantation results in significant resolution of symptoms and signs associated with ATD that is secondary to CCh and helps identify genuine ATD dry eye that is independent of CCh. PMID- 26890669 TI - Bowman Break and Subbasal Nerve Plexus Changes in a Patient With Dry Eye Presenting With Chronic Ocular Pain and Vitamin D Deficiency. AB - PURPOSE: To report the case of a 40-year-old patient with persistent bilateral ocular pain and discomfort for 2 years in whom conventional management of dry eye had failed. Detailed ocular examination, meibography, and tear film evaluation were suggestive of bilateral meibomian gland dysfunction and evaporative dry eye. Topical medication failed to alleviate the patient's symptoms. To identify the cause of pain, imaging was performed with in vivo confocal microscopy and anterior segment spectral domain optical coherence tomography. Systemic evaluation revealed severe vitamin D deficiency with a value of 5.86 ng/mL. METHODS: Case report. RESULTS: In vivo confocal microscopy showed abnormal subbasal nerve plexus morphology, increased dendritic cell density, and enlarged terminal nerve sprouts. A breach in the Bowman layer was detected in both eyes on spectral domain optical coherence tomography. Conventional management having failed, LipiFlow treatment (TearScience, Morrisville, NC) was performed and topical therapy with cyclosporine 0.05%, steroids, and lubricating eye drops was initiated with incomplete symptomatic relief. However, with parenteral therapy for vitamin D deficiency, there was a dramatic improvement in the patient's symptoms. CONCLUSIONS: Inflammation aggravated by vitamin D deficiency results in an altered epithelial profile, Bowman layer damage, recruitment of dendritic cells, and altered subbasal nerve plexus features in patients with chronic dry eye disease. These can serve as potential imaging markers for studying the underlying mechanisms in patients with dry eye disease with persisting symptoms despite aggressive conventional treatment. PMID- 26890670 TI - Structural brain injury in patients with disorders of consciousness: A voxel based morphometry study. AB - MAIN OBJECTIVE: Disorders of consciousness (DOC; encompassing coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state minus/plus (MCS-/+)) are associated with structural brain injury. The extent of this damage remains poorly understood and merits a detailed examination using novel analysis techniques. Research design/methods and procedures: This study used voxel-based morphometry (VBM) on structural magnetic resonance imaging scans of 61 patients with DOC to examine grey and white matter injury associated with DOC, time spent in DOC, aetiology and diagnosis. MAIN OUTCOMES AND RESULTS: DOC and time spent in DOC were found to be associated with widespread structural brain injury, although the latter did not correlate strongly with injury in the right cerebral hemisphere. Traumatic, as compared to non-traumatic aetiology, was related to more injury in the brainstem, midbrain, thalamus, hypothalamus, basal forebrain, cerebellum, and posterior corpus callosum. Potential structural differences were found between VS/UWS and MCS and between MCS- and MCS+, but need further examination. CONCLUSIONS: The findings indicate that both traumatic and non-traumatic DOC are associated with widespread structural brain injury, although differences exist that could lead to aetiology-specific treatment strategies. Furthermore, the high degree of atrophy occurring after initial brain injury prompts the development and use of neuroprotective techniques to potentially increase patients' chances of recovery. PMID- 26890671 TI - Trajectories of Callous-Unemotional Traits in Childhood Predict Different Forms of Peer Victimization in Adolescence. AB - Callous-unemotional (CU) traits (e.g., lack of empathy and guilt) differentiate a group of children at particularly high risk for engaging in aggressive behavior, notably bullying. However, little is known about whether youths with CU traits are at risk for being victimized by their peers. We examined the associations between trajectories of CU traits in childhood (between 7 and 12 years old) and peer victimization in adolescence (14 years old). The participants were drawn from the Twins Early Development Study, a longitudinal population-based study of twins born in England and in Wales. The trajectories of CU traits (i.e., stable high, increasing, decreasing and stable low) were identified through general growth mixture modeling. Four forms of peer victimization were considered: physical victimization, verbal victimization, social manipulation, and attacks on property. We found that youths with stable high levels, increasing levels, and decreasing levels of CU traits in childhood had higher levels of physical victimization in adolescence, not explained by other predictors at age 7 (e.g., conduct problems). Youths with increasing levels of CU traits, compared with the ones with stable low levels, also had higher levels of verbal victimization, social manipulation, and attacks on property. Our findings highlight the importance of distinct trajectories of CU traits in accounting for the experience of different forms of peer victimization. Youths with CU traits may benefit from bullying prevention programs, as they are likely to be the targets of peer victimization. PMID- 26890673 TI - Assessment of Cognitive Functioning after Pallidotomy in Patients with Primary Dystonia. AB - BACKGROUND: Stereotactic pallidotomy in the treatment of primary dystonia results in permanent damage to the posteroventral region of the internal globus pallidus. Lesions within the basal ganglia may change cognitive functioning. Subcortical structures interact with the frontal cortex, which plays an important role in cognition. OBJECTIVES: The aim of this study is to evaluate the effect of stereotactic pallidotomy on cognitive function in patients with primary dystonia. METHODS: Thirty patients with primary dystonia who qualified for pallidotomy were tested 1-2 days before surgery, 2 days after surgery and a third time after about 6 months from the date of surgery. Cognitive functioning was assessed by the following tests: Benton visual short-term memory, auditory verbal learning test, trail making test, Stroop color word interference test and Wisconsin card sorting test. RESULTS: Statistical analysis showed the deterioration of the auditory verbal learning process in the early postoperative period of patients with primary dystonia, but after 6 months there was a significant improvement. After pallidotomy there were no significant differences in the efficiency of short-term visual memory, verbal and visual-spatial working memory, psychomotor speed and executive functions. CONCLUSIONS: Stereotactic pallidotomy used in the treatment of primary dystonia is a safe treatment for the cognitive functioning of patients. PMID- 26890672 TI - High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity. AB - OBJECTIVE: High-fat diet (HFD) consumption causes obesity, which is associated with well-known increased health risks. Moreover, obesity has been associated with altered sensorimotor and emotional behaviors of humans and mice. This study attempted to dissociate the influence of HFD-induced obesity on behaviors from the influence of HFD consumption itself. METHODS: C57BL male mice were randomly allocated to a low-fat diet (LFD) group, an HFD-induced obesity (DIO) group, or a pair-fed HFD-feeding nonobese (HFD) group. A comprehensive behavioral test battery was performed on all three groups to assess sensorimotor functions, anxiety- and depression-like behaviors, reward-related behaviors, social behaviors, and learning/memory functions. RESULTS: Both the DIO and HFD groups exhibited disturbed olfaction, blunted ethanol preference, and enhanced social interactions. The DIO group exhibited blunted sucrose preference, shorter latency before falling off during the rotarod test, and a lower response to mechanical stimuli. CONCLUSIONS: The HFD-fed nonobese mice showed altered behaviors related to olfaction, social interactions, and rewards that were similar to those of the DIO mice. This finding suggests that HFD consumption alters a variety of behaviors independent of obesity. PMID- 26890674 TI - Recent advances in pediatric rheumatology: January-March 2015. PMID- 26890676 TI - Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines. AB - The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage vs. thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor): For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation);For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation).For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin: The advice for warfarin is fundamentally unchanged from BSG 2008 guidance. Direct Oral Anticoagulants (DOAC): For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation). For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken >= 48 hours before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30 - 50 mL/min we recommend that the last dose of DOAC be taken 72 hours before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID- 26890677 TI - Effects of the position and number of bromine substituents on the concentration mediated 2D self-assembly of phenanthrene derivatives. AB - The effects of the position and number of bromine substituents on the self assembled patterns of phenanthrene derivatives by changing multiple weak intermolecular interactions were investigated at the 1-octanoic acid/graphite interface at different concentrations by scanning tunneling microscopy. Two Br substituted DBHP molecules (2,7-DBHP, 3,6-DBHP) and BHP without a Br group formed a linear lamellar pattern by the van der Waals interactions between the alkoxyl chains in each lamella at high concentrations, which forces the phenanthrene derivatives to self-organize in a pi-pi stacked edge-on conformation. On decreasing the solution concentration, owing to the molecule-molecule van der Waals force and BrBr halogen bonds or the molecule-solvent cooperative BrO (C[double bond, length as m-dash]O) hydrogen and BrHO-hydrogen bonds, 2,7-DBHP molecules were found to form two kinds of network structures, whereas 3,6-DBHP molecules formed only a zigzag pattern due to the intermolecular BrBr van der Waals type interactions. One bromine substituted phenanthrene derivative (3-DBHP) formed a dislocated linear pattern by two C-HBr hydrogen bonds in each dimer. These observations revealed that an important modification of the position and number of halogen substituents might dramatically change the self-assembly behaviors by different intermolecular interactions including BrBr and BrO halogen bonding, BrBr van der Waals type interactions, and HBr hydrogen bonding. DFT calculations were explored to unravel how slightly tuning the molecular structure defines the geometry of a 2D self-assembled nanoarchitecture through the different elementary structural units having BrBr and BrH interactions. PMID- 26890675 TI - Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance. AB - Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th generation cephalosporins. PMID- 26890678 TI - Pavlovian Conditioned Approach Training in Rats. AB - Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience, or the transformation of neutral stimuli into attractive, "wanted' stimuli capable of motivating behavior. Pavlovian conditioned approach (PCA) develops after the response-independent presentation of a conditioned stimulus (CS; e.g., a lever) that predicts the delivery of an unconditioned stimulus (US; e.g., a food pellet) and can be used to measure incentive salience. During training, three patterns of conditioned responses (CRs) can develop: sign-tracking behavior (CS-directed CR), goal-tracking behavior (US-directed CR), and an intermediate response (both CRs). Sign-trackers attribute incentive salience to reward-related cues and are more vulnerable to cue-induced reinstatement of drug-seeking as well as other addiction-related behaviors, making PCA a potentially valuable procedure for studying addiction vulnerability. Here, we describe materials and methods used to elicit PCA behavior from rats as well as analyze and interpret PCA behavior in individual experiments. PMID- 26890679 TI - Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons. AB - A protocol is described for sequencing the transcriptome of a cell nucleus. Nuclei are isolated from specimens and sorted by FACS, cDNA libraries are constructed and RNA-seq is performed, followed by data analysis. Some steps follow published methods (Smart-seq2 for cDNA synthesis and Nextera XT barcoded library preparation) and are not described in detail here. Previous single-cell approaches for RNA-seq from tissues include cell dissociation using protease treatment at 30 degrees C, which is known to alter the transcriptome. We isolate nuclei at 4 degrees C from tissue homogenates, which cause minimal damage. Nuclear transcriptomes can be obtained from postmortem human brain tissue stored at -80 degrees C, making brain archives accessible for RNA-seq from individual neurons. The method also allows investigation of biological features unique to nuclei, such as enrichment of certain transcripts and precursors of some noncoding RNAs. By following this procedure, it takes about 4 d to construct cDNA libraries that are ready for sequencing. PMID- 26890680 TI - Study of in vivo catheter biofilm infections using pediatric central venous catheter implanted in rat. AB - Venous access catheters used in clinics are prone to biofilm contamination, contributing to chronic and nosocomial infections. Although several animal models for studying device-associated biofilms were previously described, only a few detailed protocols are currently available. Here we provide a protocol using totally implantable venous access ports (TIVAPs) implanted in rats. This model recapitulates all phenomena observed in the clinic, and it allows bacterial biofilm development and physiology to be studied. After TIVAP implantation and inoculation with luminescent pathogens, in vivo biofilm formation can be monitored in situ, and biofilm biomass can be recovered from contaminated TIVAP and organs. We used this protocol to study host responses to biofilm infection, to evaluate preventive and curative antibiofilm strategies and to study fundamental biofilm properties. For this procedure, one should expect ~3 h of hands-on time, including the implantation in one rat followed by in situ luminescence monitoring and bacterial load estimation. PMID- 26890682 TI - A rare gallbladder ciliated foregut cyst in chronic cholecystitis. AB - INTRODUCTION: Ciliated foregut cysts (CFC) are rare anomalies due to aberrant embryological development. It is thought to arise from a remnant of the embryologic foregut. The solitary cysts are characterised by ciliated pseudostratified columnar epithelium. They are usually located above the diaphragm but they can also arise in relation to the liver, gallbladder and pancreas. PRESENTATION OF CASE: We present the first ciliated foregut cyst of the gallbladder case reported in Australia, and the ninth known case to be reported worldwide. A 61-year-old male with chronic cholecystitis and cholelithiasis underwent an elective laparoscopic cholecystectomy and intraoperative cholangiogram. Intraoperatively, 'out-pouching' was noted on the lateral border of the gallbladder. Microscopically the histopathology showed that the cyst was lined by ciliated columnar epithelium the characteristic feature of a ciliated foregut cyst. DISCUSSION: To date only 8 cases of these ciliated foregut cysts in the gallbladder have been reported in literature. Our case is the first reported in Australia. It is unique in that the patient was an older male as opposed to most other previous cases, which were younger females. These cysts can be difficult to distinguish from neoplasms clinically and radiographically. Reports have shown that these cysts may become dysplastic and is best excised when discovered. CONCLUSION: Despite the rarity of CFCs and their potential to mimic malignancy, we propose awareness and understanding of the management for them being excision and hopefully not cause any confusion or devastatingly allow it to become malignant. PMID- 26890681 TI - A cryoinjury model in neonatal mice for cardiac translational and regeneration research. AB - The introduction of injury models for neonatal mouse hearts has accelerated research on the mechanisms of cardiac regeneration in mammals. However, some existing models, such as apical resection and ligation of the left anterior descending artery, produce variable results, which may be due to technical difficulties associated with these methods. Here we present an alternative model for the study of cardiac regeneration in neonatal mice in which cryoinjury is used to induce heart injury. This model yields a reproducible injury size, does not induce known mechanisms of cardiac regeneration and leads to a sustained reduction of cardiac function. This protocol uses reusable cryoprobes that can be assembled in 5 min, with the entire procedure taking 15 min per pup. The subsequent heart collection and fixation takes 2 d to complete. Cryoinjury results in a myocardial scar, and the size of injury can be scaled by the use of different cryoprobes (0.5 and 1.5 mm). Cryoinjury models are medically relevant to diseases in human infants with heart disease. In summary, the myocardial cryoinjury model in neonatal mice described here is a useful tool for cardiac translational and regeneration research. PMID- 26890684 TI - Nitrogen, Phosphorus, and Sulfur Co-Doped Hollow Carbon Shell as Superior Metal Free Catalyst for Selective Oxidation of Aromatic Alkanes. AB - Metal-free heteroatom-doped carbocatalysts with a high surface area are desirable for catalytic reactions. In this study, we found an efficient strategy to prepare nitrogen, phosphorus, and sulfur co-doped hollow carbon shells (denote as NPS HCS) with a surface area of 1020 m(2) g(-1). Using a poly(cyclotriphosphazene-co 4,4'-sulfonyldiphenol) (PZS) shell as carbon source and N, P, S-doping source, and the ZIF-67 core as structural template as well as extra N-doping source, NPS HCS were obtained with a high surface area and superhydrophilicity. All these features render the prepared NPS-HCS a superior metal-free carbocatalyst for the selective oxidation of aromatic alkanes in aqueous solution. This study provides a reliable and facile route to prepare doped carbocatalysts with enhanced catalytic properties. PMID- 26890683 TI - Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador. AB - OBJECTIVE: In a primary human papillomavirus (HPV) screening program, we compared the 6-month follow-up among colposcopy and noncolposcopy-based management strategies for screen-positive women. MATERIALS AND METHODS: Women aged 30 to 49 years were screened with HPV DNA tests using both self-collection and provider collection of samples. Women testing positive received either (1) colposcopy management (CM) consisting of colposcopy and management per local guidelines or (2) screen-and-treat (ST) management using visual inspection with acetic acid to determine cryotherapy eligibility, with eligible women undergoing immediate cryotherapy. One thousand women were recruited in each cohort. Of these, 368 (18.4%) of 2000 women were recruited using a more intensive outreach strategy. Demographics, HPV positivity, and treatment compliance were compared across recruitment and management strategies. RESULTS: More women in the ST cohort received treatment within 6 months compared with those in the CM cohort (117/119 [98.3%] vs 64/93 [68.8%]; p < .001). Women recruited through more intensive outreach were more likely to be HPV positive, lived in urban areas, were more educated, and had higher numbers of lifetime sexual partners and fewer children. CONCLUSIONS: Women in the CM arm were less likely to complete care than women in the ST arm. Targeted outreach to underscreened women successfully identified women with higher prevalence of HPV and possibly higher disease burden. PMID- 26890686 TI - Hydrogen sensing characteristics from carbon nanotube field emissions. AB - An innovative hydrogen sensing concept is demonstrated based on the field emission from multi-walled carbon nanotubes, where the low emission currents rise in proportion to hydrogen partial pressures above 10(-9) Torr. Experimental and first principles studies reveal that the sensing mechanism is attributed to the effective work function reduction from dissociative hydrogen chemisorption. The embedded Ni catalyst would assist both the hydrogen dissociation and work function reduction. This technique is promising to build miniature low cost hydrogen sensors for multiple applications. This work is valuable for studies of nanocarbon-gas reaction mechanisms and the work function properties in adsorption related applications, including field emission, hydrogen storage, energy cells, and gas sensing. PMID- 26890685 TI - HPV vaccination: Population approaches for improving rates. AB - OBJECTIVE: To review the literature on interventions to increase HPV vaccinations and assess whether The Community Preventive Services Task Force recommendations are supported by current evidence. METHODS: We used a PubMed search to identify studies that assessed interventions that looked at provider assessment and feedback, provider reminders, client reminder and recall, and clinic based education programs. RESULTS: Of the 13 studies identified, 8 included client reminder and recall interventions, 4 included provider assessment and feedback and/or provider reminders and 2 included clinic based education. 11 of the 13 studies demonstrated a positive effect on HPV vaccine initiation or completion. Provider assessment and feedback studies were more likely to report a positive effect on HPV vaccine initiation than on series completion, while client reminder recall interventions more frequently produced an effect on series completion than on initiation. CONCLUSIONS: There is evidence to support the application of the Community Preventive Services Task Force recommendations specifically to HPV vaccination both for client reminder and recall programs and for provider assessment and feedback interventions. Multiple targeted approaches will be needed to substantially impact HPV vaccine rates. PMID- 26890689 TI - Beta-blockers in 2016: Still the safest and most useful drugs for portal hypertension? PMID- 26890687 TI - How compensation breaks down in Parkinson's disease: Insights from modeling of denervated striatum. AB - The bradykinesia and other motor signs of Parkinson's disease (PD) are linked to progressive loss of substantia nigra dopamine (DA) neurons innervating the striatum. However, the emergence of idiopathic PD is likely preceded by a prolonged subclinical phase, which may be masked by a variety of pre- and postsynaptic compensatory mechanisms. It is often considered self-evident that the signs of PD manifest only when nigrostriatal degeneration has proceeded to such an extent that putative compensatory mechanisms fail to accommodate the depletion of striatal DA levels. However, the precise nature of the compensatory mechanisms, and the reason for their ultimate failure, has been elusive. In a recent computational study we modeled the effects of progressive denervation, including changes in the dynamics of interstitial DA and also adaptive or compensatory changes in postsynaptic responsiveness to DA signaling in the course of progressive nigrostriatal degeneration. In particular, we found that failure of DA signaling can occur by different mechanisms at different disease stages. We review these results and discuss their relevance for clinical and translational research, and we draw a number of predictions from our model that might be tested in preclinical experiments. PMID- 26890690 TI - How age and gender predict illness course in a first-episode nonaffective psychosis cohort. AB - OBJECTIVE: Male gender and young age at onset of schizophrenia are traditionally associated with poor treatment outcome and often used to determine prognosis. However, many studies use nonincident samples and fail to adjust for symptom severity at onset. We hypothesized that age and gender would influence severity of presentation but would not predict outcome after adjustment for symptoms at presentation. METHOD: 628 people with first-episode ICD-9 and DSM-IV nonaffective psychosis from 2 historical cohorts recruited from sequential presentations in Canada and the United Kingdom (1996-1998) were assessed prospectively at presentation and over 12-18 months using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Models of the age-at-onset distributions with 2 underlying modes at similar ages in women (ages 23 years and 47 years) and men (ages 22 years and 46 years) had relatively good fits compared to single-mode models (chi(2)1 better by 9.2 for females, 8.0 for males, both P < .05). At presentation, scores for negative symptoms were 1.84 points worse for males (95% CI, 1.05 to 2.58; P < .001) in a mixed effects model. Younger age also predicted higher negative scores at presentation (partial correlation r = -0.18, P < .01; P < .001 in the mixed effects model). Findings were similar for cognitive disorganized symptoms. However, after controlling for baseline symptoms, age at onset and gender did not significantly predict subsequent symptom course in the mixed effects models. CONCLUSIONS: Gender and age at onset are independently associated with symptoms at presentation but not with medium-term course of schizophrenia. This finding reinforces the importance of early identification and prevention of severe negative symptoms at first episode, whatever an individual's age and gender. PMID- 26890691 TI - Ultrastable polyethyleneimine-stabilized gold nanoparticles modified with polyethylene glycol for blood pool, lymph node and tumor CT imaging. AB - Development of new long-circulating contrast agents for computed tomography (CT) imaging of different biological systems still remains a great challenge. Here, we report the design and synthesis of branched polyethyleneimine (PEI)-stabilized gold nanoparticles (Au PSNPs) modified with polyethylene glycol (PEG) for blood pool, lymph node, and tumor CT imaging. In this study, thiolated PEI was first synthesized and used as a stabilizing agent to form AuNPs. The formed Au PSNPs were then grafted with PEG monomethyl ether via PEI amine-enabled conjugation chemistry, followed by acetylation of the remaining PEI surface amines. The formed PEGylated Au PSNPs were characterized via different methods. We show that the PEGylated Au PSNPs with an Au core size of 5.1 nm have a relatively long half decay time (7.8 h), and display a better X-ray attenuation property than conventionally used iodine-based CT contrast agents (e.g., Omnipaque), and are hemocompatible and cytocompatible in a given concentration range. These properties of the Au PSNPs afford their uses as a contrast agent for effective CT imaging of the blood pool and major organs of rats, lymph node of rabbits, and the xenografted tumor model of mice. Importantly, the PEGylated Au PSNPs could be excreted out of the body with time and also showed excellent in vivo stability. These findings suggest that the formed PEGylated Au PSNPs may be used as a promising contrast agent for CT imaging of different biological systems. PMID- 26890692 TI - Supramolecular Columnar Liquid Crystals with Tapered-Shape Simple Pyrazoles Obtained by Efficient Henry/Michael Reactions. AB - A straightforward synthesis of mesogenic pyrazoles starting from benzaldehydes by a combination of efficient Henry and Michael reactions led to novel supramolecular liquid crystals. The mesogens are fluorescent 3,5-dimethyl-4-(di or trialkoxyphenyl)pyrazoles and, in spite of the tapered shape of these molecules and their structural simplicity (only one phenyl ring), columnar liquid crystal phases were formed that are stable at room temperature. The self assembled structure was studied by XRD and the columnar cross section contains two molecules on average with an antiparallel arrangement of pyrazoles interacting through hydrogen bonds. In contrast, the single-crystal structure of a trimethoxy analog did not show hydrogen-bonded pyrazoles but chains of head-to tail arranged molecules. PMID- 26890693 TI - A data-driven allocation tool for in-kind resources distributed by a state health department. AB - OBJECTIVE: The objective of this study was to leverage a state health department's operational data to allocate in-kind resources (children's car seats) to counties, with the proposition that need-based allocation could ultimately improve public health outcomes. METHODS: This study used a retrospective analysis of administrative data on car seats distributed to counties statewide by the Georgia Department of Public Health and development of a need-based allocation tool (presented as interactive supplemental digital content, adaptable to other types of in-kind public health resources) that relies on current county-level injury and sociodemographic data. RESULTS: Car seat allocation using public health data and a need-based formula resulted in substantially different recommended allocations to individual counties compared to historic distribution. CONCLUSIONS: Results indicate that making an in-kind public health resource like car seats universally available results in a less equitable distribution of that resource compared to deliberate allocation according to public health need. Public health agencies can use local data to allocate in-kind resources consistent with health objectives; that is, in a manner offering the greatest potential health impact. Future analysis can determine whether the change to a more equitable allocation of resources is also more efficient, resulting in measurably improved public health outcomes. PMID- 26890695 TI - How Protective Mechanisms Interact to Prevent Overnight Calcium Phosphate Precipitation - An Observational Study to Determine Factors Against Calcium Phosphate Lithogenesis in a Healthy Cohort. AB - BACKGROUND/AIMS: As restful, non-interrupted sleep is essential for normal mental and physical functioning, the urine flow rate (UFR) overnight remains low. Due to this reduced UFR, the kidneys produce a lower urine volume, which may lead to supersaturation of lithogens in the renal collecting system. The protective mechanisms that prevent the rise in the concentration of the lithogenic substances in urine, such as calcium phosphate, are explored. METHODS: Urine samples were collected from 26 subjects every 2-3 h during daylight with one nocturnal collection; the UFR was calculated in the median time for each collection period. Urinary constituents for calcium phosphate precipitation including electrolytes, calcium, phosphate, citrate, and pH were measured. Comparisons within individuals were done by paired t test. RESULTS: The calcium excretion rate fell significantly overnight (from 2.4 +/- 0.2 umol/min during the daytime to 1.5 +/- 0.3 umol/min, p < 0.05), in parallel with sodium excretion (54 +/- 16 umol/min from its daytime 127 +/- 12 umol/min, p < 0.05), preventing nocturnal calcium concentration from increasing (3.0 +/- 0.3 mmol/l daytime to 2.5 +/- 0.5 mmol/l overnight), while citrate concentration did not change significantly. The total urine phosphate concentration rose significantly overnight (daytime 18.7 +/- 1.4 umol/min vs. nocturnal 20.9 +/- 1.7 umol/min), but the concentration of divalent phosphate did not increase in the overnight period. CONCLUSIONS: Although the UFR was lower overnight, there was no evidence that the risk of calcium phosphate precipitate formation in healthy subjects was increased. PMID- 26890694 TI - Objective Assessment of Nuclear and Cortical Cataracts through Scheimpflug Images: Agreement with the LOCS III Scale. AB - PURPOSE: To assess nuclear and cortical opacities through the objective analysis of Scheimpflug images, and to check the correlation with the Lens Opacity Classification System III (LOCS III). METHODS: Nuclear and cortical opacities were graded according to the LOCS III rules after pupil dilation. The maximum and average pixel intensity values along an elliptical mask within the lens nucleus were taken to analyse nuclear cataracts. A new metric based on the percentage of opaque pixels within a region of interest was used to analyse cortical cataracts. The percentage of opaque pixels was also calculated for half, third and quarter areas from the region of interest's periphery. RESULTS: The maximum and average intensity values along the nucleus were directly proportional to the LOCS III grade: The larger the LOCS III value, the larger maximum and average intensity ones. These metrics showed a positive and significant correlation with the LOCS grade: The larger the LOCS grade, the higher was percentage of opaque pixels along the cortex within the same mask's size. This metric showed a significant correlation to the LOCS grade. CONCLUSION: The metrics used to assess nuclear opacities showed good correlation with the LOCS III. The percentage of opaque pixels showed to be a useful metric to measure objectively the severity of the cortical opacity. These metrics could be implemented in an algorithm to detect and grade lens opacities automatically and objectively. PMID- 26890696 TI - Ivabradine Prevents Low Shear Stress Induced Endothelial Inflammation and Oxidative Stress via mTOR/eNOS Pathway. AB - Ivabradine not only reduces heart rate but has other cardiac and vascular protective effects including anti-inflammation and anti-oxidation. Since endothelial nitric oxide synthase (eNOS) is a crucial enzyme in maintaining endothelial activity, we aimed to investigate the impact of ivabradine in low shear stress (LSS) induced inflammation and endothelial injury and the role of eNOS played in it. Endothelial cells (ECs) were subjected to LSS at 2dyne/cm2, with 1 hour of ivabradine (0.04MUM) or LY294002 (10MUM) pre-treatment. The mRNA expression of IL-6, VCAM-1 along with eNOS were measured by QPCR. Reactive oxygen species (ROS) was detected by dihydroethidium (DHE) and DCF, and protein phosphorylation was detected by western blot. It demonstrated that ivabradine decreased LSS induced inflammation and oxidative stress in endothelial cells. Western blot showed reduced rictor and Akt-Ser473 as well as increased eNOS Thr495 phosphorylation. However, mTORC1 pathway was only increased when LSS applied within 30 minutes. These effects were reversed by ivabradine. It would appear that ivabradine diminish ROS generation by provoking mTORC2/Akt phosphorylation and repressing mTORC1 induced eNOS-Thr495 activation. These results together suggest that LSS induced endothelial inflammation and oxidative stress are suppressed by ivabradine via mTORC2/Akt activation and mTORC1/eNOS reduction. PMID- 26890697 TI - Automated, high-throughput, in vivo analysis of visual function using the zebrafish. AB - BACKGROUND: Modern genomics has enabled the identification of an unprecedented number of genetic variants, which in many cases are extremely rare, associated with blinding disorders. A significant challenge will be determining the pathophysiology of each new variant. The Zebrafish is an excellent model for the study of inherited diseases of the eye. By 5 days post-fertilization (dpf), they have quantifiable behavioral responses to visual stimuli. However, visual behavior assays can take several hours to perform or can only be assessed one fish at a time. RESULTS: To increase the throughput for vision assays, we used the Viewpoint Zebrabox to automate the visual startle response and created software, Visual Interrogation of Zebrafish Manipulations (VIZN), to automate data analysis. This process allows 96 Zebrafish larvae to be tested and resultant data to be analyzed in less than 35 minutes. We validated this system by disrupting function of a gene necessary for photoreceptor differentiation and observing decreased response to visual stimuli. CONCLUSIONS: This automated method along with VIZN allows rapid, high-throughput, in vivo testing of Zebrafish's ability to respond to light/dark stimuli. This allows the rapid analysis of novel genes involved in visual function by morpholino, CRISPRS, or small-molecule drug screens. Developmental Dynamics 245:605-613, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890699 TI - Taking care of the future for contact lenses. PMID- 26890700 TI - Effects of multipurpose solutions on the adhesion of Acanthamoeba to rigid gas permeable contact lenses. AB - PURPOSE: To evaluate the effect of multipurpose contact lens care solutions (MPSs) on the adhesion of Acanthamoeba to rigid gas permeable (RGP) contact lenses. METHODS: Acanthamoeba castellanii (AC) trophozoites were inoculated onto untreated RGP contact lenses (FP, Extra, or Menicon Z), and numbers of trophozoites adhering to lenses were counted under a phase contrast microscope at 18 h post-inoculation (controls). Similarly, adhering trophozoites were counted at 6 h post-inoculation on each of the three RGP lens types with one of three MPSs (Boston Simplus, Menicare Plus, and O2 Care). Scanning electron microscopic examinations were performed to compare lens surfaces. RESULTS: Adhesion of AC trophozoites to untreated FP was greater than to untreated Extra or Menicon Z. Surfaces of Extra and Menicon Z lenses were waxier, smoother, and more homogeneous than those of FP lenses. After treatment with Boston Simplus, adhesion of AC trophozoites was significantly reduced for all lens types as compared with controls (p < 0.0001). Treatments with Menicare Plus or O2 Care reduced the number of adherent AC trophozoites significantly on FP lenses only as compared with controls (p < 0.0001). CONCLUSIONS: The adhesion rates of AC trophozoites to RGP lenses depended on lens surfaces. Boston Simplus reduced the adhesion rate of AC trophozoites more than Menicare Plus or O2 Care. Appropriate RGP lens and MPS selection could decrease the prevalence of Acanthamoeba keratitis. PMID- 26890701 TI - Impact of duration of contact lens wear on the structure and function of the meibomian glands. AB - PURPOSE: To investigate the effects of the duration of contact lens (CL) wear on the meibomian glands (MGs), eyelid and tear film. METHODS: This was a cross sectional study of CL wearers and non-wearers (NWs) aged between 18 and 35 years. The sample comprised of: (i) Three groups of CL wearers of different duration profiles (short, moderate and long experience of CL wear); (ii) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months prior to the present study; (iii) healthy non-wearers as a control group. Study procedures were conducted in the order from least invasive to most invasive as follows: symptom assessment, lipid assessment, non-invasive break-up time, tear meniscus area, tear osmolarity and evaporation, Phenol red thread, MG expressibility, ocular surface and eyelid assessments, meibography, Marx line and lid wiper assessment using lissamine green. For statistical comparison of continuous data, one-way analysis of variance was used with Bonferroni post-hoc correction, where appropriate. Kruskal-Wallis test and Pearson Chi-Square respectively were used for ordinal and categorical variables. RESULTS: A total of 100 participants (49 males and 51 females; mean age +/- SD: 25.4 +/- 4.1) were enrolled across the five groups, such that each was composed of 20 age/sex matched individuals. Significant differences between the study groups were found for MG expressibility (p < 0.001), number of plugged orifices (p = 0.001), number of expressed orifices (p < 0.001), MG dropout (p = 0.001), Marx line score (p < 0.001), palpebral redness (p = 0.003), and roughness (p = 0.002), non-invasive break-up time (p < 0.001), Phenol red thread (p = 0.005), and tear meniscus area (p = 0.029). For all these variables, the NW group was statistically different from all other groups. Duration of wear was not a significant factor, except for Marx line score which was different in PWs compared to those with longer experience of CL wear (p = 0.03) CONCLUSION: Alterations to MG morphology and function accompany contact lens wear. Although these changes onset during the first 2 years of wear, prolonged CL exposure beyond this point does not appear to be associated with further modification. Cessation of wear for at up to 6 months does not lead to resolution. PMID- 26890702 TI - Assessing ocular bulbar redness: a comparison of methods. AB - PURPOSE: We consider whether quantification of ocular bulbar redness, using image processing of relative Red-channel activity (Red-value), can be applied to a clinical sample and how this approach compares to an automated bulbar redness grading technique (Oculus Keratograph 5M, R-scan). METHODS: Red-values from dry eye patients (n = 25) were determined using image processing of digital photographs over the nasal bulbar conjunctiva. Red-values were compared with subjective grades from six clinicians who graded the images using the IER scale. We considered the level of agreement between the Red-value and automated bulbar redness scores from the commercial instrument (R-scan). Scoring variability for each technique was assessed using the geometric coefficient of variation (gCoV, %). Agreement between techniques was considered with Bland-Altman analyses. RESULTS: Red-values showed a strong linear relationship (R(2) = 0.99) to the R scan. The Red-value had least variability (gCoV = 0.97%, 95% CI: 0.76-1.35%). The IER grade showed a linear relationship with Red-value (R(2) = 0.99), bound by a floor effect; it did not discriminate changes in redness below a threshold of 1.75 units (Red-value = 33.0%), after which it paralleled the redness returned by the R-scan. Intra-method variability for the redness returned by the R-scan (gCoV = 9.84%, 95% CI: 7.60-13.94%) and IER grades (gCoV = 7.30%, 95% CI: 1.73-10.31%) was similar (p > 0.05). Bland-Altman analysis showed the R-scan was consistently biased towards lower absolute redness scores than the IER. CONCLUSIONS: Digital imaging processing, using relative Red-channel activity, was the least variable of the three techniques. The R-scan and IER showed similar intra-observer variability. The linear relationship between R-scan and Red-value suggests that the R-scan could be derived using similar methods. PMID- 26890703 TI - Comparing self-reported optometric dry eye clinical practices in Australia and the United Kingdom: is there scope for practice improvement? AB - PURPOSE: The aim of this study was to compare the self-reported clinical practice behaviours of optometrists in Australia and the United Kingdom (UK) with respect to the diagnosis and management of dry eye disease (DED). We also sought to examine whether the reported practices of clinicians in each region were consistent with current evidence-based recommendations for DED. METHODS: An online survey was distributed to optometrists (Australia, n = 654; UK, n = 1006). Respondents provided information about practice modality, years of optometric experience, preferred diagnostic and management strategies (stratified by DED severity) and the information/evidence base used to guide patient care. RESULTS: A total of 317 completed surveys were received (response rates, Australia: 21%, UK: 17%). Optometrists in both regions demonstrated similarly strong knowledge of tear film assessment and adopted both subjective and objective techniques to diagnose DED. Patient symptoms were considered the most important, valuable and commonly performed assessment by both Australian and UK respondents. UK practitioners valued and utilised conjunctival signs and tear meniscus height assessments more than Australian optometrists (p < 0.05), who placed relatively greater emphasis on sodium fluorescein tear break-up time to diagnose DED (p < 0.05). Clinicians in both locations tailored DED therapy to severity. While practitioners in both regions predominantly managed mild DED with eyelid hygiene and tear supplementation, Australian optometrists indicated prescribing topical corticosteroid therapy significantly more often than UK practitioners for moderate (14% vs 6%) and severe (52% vs 8%) disease (p < 0.05). The major source of information used to guide practitioners' dry eye management practices was continuing education conferences. CONCLUSIONS: This study highlights a range of parallels and divergences in dry eye clinical practice between Australian and UK optometrists. Our data identify both areas of strength in the adoption of evidence-based practice, as well as some potential to improve international translation of dry eye research evidence into practice. PMID- 26890704 TI - Correction to: The short-term accommodation response to aniso-accommodative stimuli in isometropia. PMID- 26890698 TI - Mechanisms of microglial activation in models of inflammation and hypoxia: Implications for chronic intermittent hypoxia. AB - Chronic intermittent hypoxia (CIH) is a hallmark of sleep apnoea, a condition associated with diverse clinical disorders. CIH and sleep apnoea are characterized by increased reactive oxygen species formation, peripheral and CNS inflammation, neuronal death and neurocognitive deficits. Few studies have examined the role of microglia, the resident CNS immune cells, in models of CIH. Thus, little is known concerning their direct contributions to neuropathology or the cellular mechanisms regulating their activities during or following pathological CIH. In this review, we identify gaps in knowledge regarding CIH induced microglial activation, and propose mechanisms based on data from related models of hypoxia and/or hypoxia-reoxygenation. CIH may directly affect microglia, or may have indirect effects via the periphery or other CNS cells. Peripheral inflammation may indirectly activate microglia via entry of pro inflammatory molecules into the CNS, and/or activation of vagal afferents that trigger CNS inflammation. CIH-induced release of damage-associated molecular patterns from injured CNS cells may also activate microglia via interactions with pattern recognition receptors expressed on microglia. For example, Toll-like receptors activate mitogen-activated protein kinase/transcription factor pathways required for microglial inflammatory gene expression. Although epigenetic effects from CIH have not yet been studied in microglia, potential epigenetic mechanisms in microglial regulation are discussed, including microRNAs, histone modifications and DNA methylation. Epigenetic effects can occur during CIH, or long after it has ended. A better understanding of CIH effects on microglial activities may be important to reverse CIH-induced neuropathology in patients with sleep disordered breathing. PMID- 26890705 TI - Direct Acylation of C(sp(3))-H Bonds Enabled by Nickel and Photoredox Catalysis. AB - Using nickel and photoredox catalysis, the direct functionalization of C(sp(3))-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of alpha-amino ketones at room temperature and is amenable to late stage coupling of complex and biologically relevant groups. C(sp(3))-H activation occurs by photoredox-mediated oxidation to generate alpha-amino radicals which are intercepted by nickel in catalytic C(sp(3))-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross coupling while avoiding limitations commonly associated with transition-metal mediated C(sp(3))-H activation, including requirements for chelating directing groups and high reaction temperatures. PMID- 26890706 TI - A methodological approach to short-term tracking of youth physical fitness: the Oporto Growth, Health and Performance Study. AB - In this paper, three different statistical approaches were used to investigate short-term tracking of cardiorespiratory and performance-related physical fitness among adolescents. Data were obtained from the Oporto Growth, Health and Performance Study and comprised 1203 adolescents (549 girls) divided into two age cohorts (10-12 and 12-14 years) followed for three consecutive years, with annual assessment. Cardiorespiratory fitness was assessed with 1-mile run/walk test; 50 yard dash, standing long jump, handgrip, and shuttle run test were used to rate performance-related physical fitness. Tracking was expressed in three different ways: auto-correlations, multilevel modelling with crude and adjusted model (for biological maturation, body mass index, and physical activity), and Cohen's Kappa (kappa) computed in IBM SPSS 20.0, HLM 7.01 and Longitudinal Data Analysis software, respectively. Tracking of physical fitness components was (1) moderate to-high when described by auto-correlations; (2) low-to-moderate when crude and adjusted models were used; and (3) low according to Cohen's Kappa (kappa). These results demonstrate that when describing tracking, different methods should be considered since they provide distinct and more comprehensive views about physical fitness stability patterns. PMID- 26890708 TI - Effect of laryngopharyngeal reflux on the improvement of chronic rhinosinusitis without polyposis after primary endoscopic sinus surgery. AB - OBJECTIVES: This study aims to investigate the influence of laryngopharyngeal reflux on the improvement of chronic rhinosinusitis (CRS) in patients who underwent endoscopic sinus surgery (ESS). PATIENTS AND METHODS: A total of 48 patients (28 males, 20 females; mean age 41.6+/-15.1 years; range 18 to 75 years) with CRS without polyposis were assessed for the presence of gastric reflux with Reflux Symptom Index (RSI) and Reflux Finding Scores (RFS) before undergoing primary ESS. Patients with a RSI >12 and RFS >7 were included in the reflux(+) and those with either score under these cutoffs in the reflux(-) group. Improvement scores were accepted as the difference between preoperative scores and postoperative sixth-month Lund-Mackay Radiology Scores, Lund-Kennedy Endoscopy Scores (LKES), and Sinusitis Symptom Scores (SSS). RESULTS: There was no significant difference between improvements of the reflux(+) and reflux(-) groups in terms of radiology, endoscopy, and symptom scores (p>0.05). However, preoperative and postoperative six-month radiology scores were significantly higher in reflux(+) patients (p<0.01). Also, postoperative six-month LKES were significantly higher in reflux(+) patients. No statistically significant differences were detected between preoperative and postoperative six-month SSS in reflux(+) or reflux(-) patients. CONCLUSION: Laryngopharyngeal reflux was associated with worse radiology and endoscopy scores in CRS without polyposis; however, it had no role on the improvement scores after primary ESS. PMID- 26890707 TI - Purine (N)-Methanocarba Nucleoside Derivatives Lacking an Exocyclic Amine as Selective A3 Adenosine Receptor Agonists. AB - Purine (N)-methanocarba-5'-N-alkyluronamidoriboside A3 adenosine receptor (A3AR) agonists lacking an exocyclic amine resulted from an unexpected reaction during a Sonogashira coupling and subsequent aminolysis. Because the initial C6-Me and C6 styryl derivatives had unexpectedly high A3AR affinity, other rigid nucleoside analogues lacking an exocyclic amine were prepared. Of these, the C6-Me-(2 phenylethynyl) and C2-(5-chlorothienylethynyl) analogues were particularly potent, with human A3AR Ki values of 6 and 42 nM, respectively. Additionally, the C2-(5-chlorothienyl)-6-H analogue was potent and selective at A3AR (MRS7220, Ki 60 nM) and also completely reversed mouse sciatic nerve mechanoallodynia (in vivo, 3 MUmol/kg, po). The lack of a C6 H-bond donor while maintaining A3AR affinity and efficacy could be rationalized by homology modeling and docking of these hypermodified nucleosides. The modeling suggests that a suitable combination of stabilizing features can partially compensate for the lack of an exocyclic amine, an otherwise important contributor to recognition in the A3AR binding site. PMID- 26890709 TI - Pepsinogen identification in the middle ear fluid of children with otitis media with effusion. AB - OBJECTIVES: This study aims to investigate the presence and concentration of pepsin/pepsinogen in middle ear fluid and to discuss the potential mechanisms involved in the pathogenesis of this condition. PATIENTS AND METHODS: A total of 33 children (21 boys, 12 girls; mean age 5.7+/-2.4 years; range 3 to 13 years) diagnosed with otitis media with effusion and scheduled for operation were enrolled into the study. Fluids aspirated from the middle ear were assessed for the presence of pepsinogen and albumin and blood samples were drawn simultaneously for comparison. RESULTS: Mean pepsinogen concentration was statistically significantly higher in middle ear fluids compared with serum samples (262.4 ng/mL [range: 211.7 ng/mL - 301.1 ng/mL] versus 102.6 ng/mL [range: 80.7 ng/mL - 134.5 ng/mL], respectively) (p<0.001). On the other hand, mean albumin concentration was significantly lower (1.1 g/dL [range: 0.01 g/dL - 9.5 g/dL] versus 5.8 g/dL [range: 0.9 - 9.5 g/dL], respectively) (p<0.001). The highest pepsinogen concentration was detected in patients with purulent effusion (275.3 ng/mL). CONCLUSION: Our findings support the theory of gastro-esophageal reflux related pepsinogen transition to the middle ear and indicate that pepsinogen may a reliable biochemical marker for the assessment of gastro esophageal reflux. PMID- 26890710 TI - [Relationship between preoperative patient learning need and anxiety of patients hospitalized at Ear Nose Throat and Head Neck Surgery clinic for surgical treatment]. AB - OBJECTIVES: This study aims to evaluate the relationship between preoperative patient learning need and anxiety in patients hospitalized at Ear Nose Throat and Head Neck Surgery (ENT and HNS) clinic for surgical treatment. PATIENTS AND METHODS: The study sample comprised 98 patients (56 males, 42 females; mean age 44.4+/-15.2 years; range 18 to 76 years) hospitalized at ENT and HNS clinic for surgical treatment. A question form prepared based on the literature, Patient Learning Needs Scale (PLNS), and State-Trait Anxiety Inventory (STAI) were used in the study which was planned as a descriptive-analytical study. RESULTS: Education level of 72.5% of the patients was until high school at the furthest. The most frequent operation indications were chronic otitis media (28.6%) and vocal cord mass/paralysis (18.4%). We detected that, of the patients, 26.5% received training only from their doctors preoperatively, 74.5% did not find the given training sufficient, and 87.8% requested to receive the training preoperatively. Patients' total PLNS score was mean 30.6+/-5.4. Scores obtained from all sub-scales were within the very significant and extremely significant categories according to the scale's Likert structure. A comparison of anxiety state with learning needs dimension scores revealed a significant relationship only between trait anxiety score and emotions dimension related to the state in univariate analysis (r=0.21, p<0.05). CONCLUSION: We detected a relationship between some dimensions of patient learning needs and anxiety level. Considering these findings, we advise that patient training programs and materials are developed and preoperative planned patient trainings are conducted. PMID- 26890711 TI - Assessment of nasal airway patency during pregnancy and postpartum period: correlation between subjective and objective techniques. AB - OBJECTIVES: This study aims to determine the physiological changes in a pregnant woman's nasal airway, the frequency of pregnancy rhinitis, and the correlation among anterior rhinoscopy (AnR), anterior rhinomanometry (ARM), and subjective nasal obstruction score as she progresses through pregnancy into the postpartum period (PPP). PATIENTS AND METHODS: Twenty non-smoking healthy pregnant women aged 19-35 (average 27.5+/-4.7) without a history of either respiratory allergy or chronic nasal or sinus problems were included in the study. Detailed history taking, AnR, and ARM were performed by the same ear nose and throat specialist at each trimester and postpartum second week. From then on, the participants scored, subjectively, morning levels of nasal obstruction (0= none, 1= slight, 2= moderate, 3= severe, 4= total obstruction). RESULTS: The AnR scores were low and the ARM findings were in normal range in the first trimester. Increasing AnR scores through pregnancy and decreasing AnR scores at PPP were statistically significant. Similarly, the ARM findings increased through pregnancy and decreased to normal levels at PPP; however, these changes among trimesters and PPP were not statistically significant. CONCLUSION: Anterior rhinomanometry and AnR are useful tools in the determination of nasal physiological changes as pregnancy progresses to PPP. PMID- 26890712 TI - Voice evaluation in asthma patients using inhaled corticosteroids. AB - OBJECTIVES: This study aims to assess voice changes and laryngeal abnormalities in asthmatic patients using inhaled corticosteroids (ICSs). PATIENTS AND METHODS: This study included 30 patients (15 females; mean age 21.3+/-2.6 years; range, 17 to 26 years and 15 males; mean age 20.7+/-2.3 years; range, 16 to 27 years) with bronchial asthma treated with ICSs between May 2013 and December 2013. A speech sample from each patient was evaluated by two phoniatricians and the degrees of dysphonia were scored. Each patient's voice was acoustically analyzed using the multidimensional voice program software. Videolaryngoscopy was used to detect laryngeal abnormalities including the vocal folds. RESULTS: A total of 53.3% of ICSs users had dysphonia; most of them had a mild degree dysphonia. Of patients, vocal folds erythema was present in 56.7%, interarytenoid thickening in 56.7%, vocal folds bowing in 5.3% and vocal fold atrophy in 5.5%. A total of 36.7% patients had manifestations of laryngopharyngeal reflux. The presence of vocal fold bowing and atrophy was significantly related to the duration of ICS use (p=0.048). Soft phonation index values were positively associated with the duration of the ICS use (p=0.013). CONCLUSION: Inhaled corticosteroids have abnormally adverse effects both on the function and the structure of the vocal folds. PMID- 26890713 TI - Well differentiated papillary carcinoma of thyroid presenting as metastatic liver mass. AB - Well differentiated papillary carcinoma of thyroid frequently metastasizes to regional lymph nodes and the patients usually present with cervical or mediastinal lymphadenopathy. In this article, we report a case of papillary thyroid carcinoma with hepatic metastasis presenting as liver mass in absence of lymph nodal metastasis, a presentation not previously reported to the best of our knowledge. PMID- 26890714 TI - Unilateral sudden hearing loss: a rare symptom of Moyamoya disease. AB - A 38-year-old female patient experienced a sudden onset of unilateral sensorineural hearing loss due to Moyamoya disease. A detailed summary of audiological and neurological findings indicated that the sudden hearing loss might be due to Moyamoya disease resulting in occlusion of posterior and middle cerebral arteries. Intravenous prednisolone and trimetazidine dihydrochloride may improve hearing thresholds and speech understanding. To our knowledge, this is the first article in the literature reporting a case of sudden hearing loss as the first manifestation of Moyamoya disease in a young adult. PMID- 26890715 TI - Rare cases of benign tumors of the head and neck: lipoma of larynx and sternocleidomastoid muscle. AB - In this article, we report two rare cases of lipoma in the head and neck region. Thirty-four-year-old case 1 presented with hoarseness and sensation of foreign body in throat. While 54-year-old case 2 presented with complaint of a mass in left side of neck. The imaging methods showed the masses in false vocal fold and the sternocleidomastoid muscle. Diagnosis and treatment of the masses were discussed in light of the literature. PMID- 26890716 TI - [Outpatient surgical practices in otorhinolaryngology]. AB - OBJECTIVES: In this study, we report outpatient surgical procedures in an ear nose and throat (ENT) clinic of a university hospital for the first time in Turkey. MATERIAL AND METHODS: All patients who were operated between January 2012 and December 2013 by our ENT surgeons either in central operating room or in outpatient surgery unit were retrospectively analyzed. Age of the patients, type of operation, type of anesthesia, and the time of discharge were recorded. RESULTS: The highest number of outpatient surgical procedures was in the 1-18 age group. The most widely used type of anesthesia was general anesthesia, while adeno/tonsillectomy and tympanostomy tube insertion were the most commonly performed operations. The total number of surgeries was 2,714 and 379 (13.96%) of these patients were discharged on the same day. CONCLUSION: Outpatient surgery has become widespread in the past three decades, particularly. However, in our study, the ratio of outpatient surgery to all surgical interventions was very low, compared to developed countries. PMID- 26890717 TI - Deep-Sea DuraFET: A Pressure Tolerant pH Sensor Designed for Global Sensor Networks. AB - Increasing atmospheric carbon dioxide is driving a long-term decrease in ocean pH which is superimposed on daily to seasonal variability. These changes impact ecosystem processes, and they serve as a record of ecosystem metabolism. However, the temporal variability in pH is observed at only a few locations in the ocean because a ship is required to support pH observations of sufficient precision and accuracy. This paper describes a pressure tolerant Ion Sensitive Field Effect Transistor pH sensor that is based on the Honeywell Durafet ISFET die. When combined with a AgCl pseudoreference sensor that is immersed directly in seawater, the system is capable of operating for years at a time on platforms that cycle from depths of several km to the surface. The paper also describes the calibration scheme developed to allow calibrated pH measurements to be derived from the activity of HCl reported by the sensor system over the range of ocean pressure and temperature. Deployments on vertical profiling platforms enable self calibration in deep waters where pH values are stable. Measurements with the sensor indicate that it is capable of reporting pH with an accuracy of 0.01 or better on the total proton scale and a precision over multiyear periods of 0.005. This system enables a global ocean observing system for ocean pH. PMID- 26890718 TI - Complex link between male lower urinary tract symptoms and metabolic syndrome: More than ethnic disparity. PMID- 26890719 TI - Estimating the Compressibility of Osmium from Recent Measurements of Ir-Os Alloys under High Pressure. AB - Several fcc- and hcp-structured Ir-Os alloys have been recently studied up to 30 GPa at room temperature by means of synchrotron-based X-ray powder diffraction in diamond anvil cells. Using their bulk moduli, which increase with increasing osmium content, showing a deviation from linearity, and after employing a thermodynamical model, it was concluded that the bulk modulus for osmium is slightly smaller than that for diamond. Here, a similar conclusion is obtained upon employing an alternative model, thus strengthening the conclusion that osmium is the densest but not the most incompressible element. This is particularly interesting for Earth Sciences because it may be of key importance toward clarifying the anomalous elastic properties of the Earth's core. PMID- 26890720 TI - Understanding the sensory irregularities of esophageal disease. AB - Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future. PMID- 26890721 TI - Three-dimensional structures of magnesium nanopores. AB - The optimization of nanopore-based devices is closely related to the nanopore three-dimensional (3D) structures. In this paper, faceted nanopores were fabricated in magnesium (Mg) by aligning the electron beam (e-beam) along the [0001] direction. Detailed structural characterization by transmission electron microscopy reveals the existence of two 3D structures: hexagonal prism-shaped and hourglass-shaped 3D morphologies. Moreover, the 3D structures of nanopores are also found to depend on the widest nanopore diameter-to-thickness ratio (D/t). A plausible formation mechanism for different 3D structures is discussed. Our results incorporate a critical piece of information regarding the nanopore 3D structures in Mg and may serve as an important design guidance for the size- and shape-controllable fabrication of solid-state nanopores applying the e-beam sculpting technique. PMID- 26890723 TI - From the Editor. PMID- 26890722 TI - Changes of microbial spoilage, lipid-protein oxidation and physicochemical properties during post mortem refrigerated storage of goat meat. AB - Examined was the effect of post mortem refrigerated storage on microbial spoilage, lipid-protein oxidation and physicochemical traits of goat meat. Seven Boer bucks were slaughtered, eviscerated and aged for 24 h. The Longissimus lumborum (LL) and Semitendinosus (ST) muscles were excised and subjected to 13 days post mortem refrigerated storage. The pH, lipid and protein oxidation, tenderness, color and drip loss were determined in LL while microbiological analysis was performed on ST. Bacterial counts generally increased with increasing aging time and the limit for fresh meat was reached at day 14 post mortem. Significant differences were observed in malondialdehyde (MDA) content at day 7 of storage. The thiol concentration significantly reduced as aging time increased. The band intensities of myosin heavy chain (MHC) and troponin-T significantly decreased as storage progressed, while actin remained relatively stable. After 14 days of aging, tenderness showed significant improvement while muscle pH and drip loss reduced with increase in storage time. Samples aged for 14 days had higher lightness (P < 0.05) and lower (P < 0.05) yellowness and redness. Post mortem refrigerated storage influenced oxidative and microbial stability and physico-chemical properties of goat meat. PMID- 26890724 TI - Unemployment, perceived health status and coping: A study in Southern Italy. AB - BACKGROUND: Unemployment is a very stressful experience that significantly impairs an individual's perception of their overall wellbeing. Interaction between unemployment and physical health is complex. OBJECTIVE: To analyze how specific coping strategies and socio-demographic variables may influence the level of physical and mental health perceived by those searching for work at an employment centre in Catanzaro, Italy. METHODS: Participants completed a set of self-administrated questionnaires including a socio-demographic questionnaire, the Coping Inventory for Stressful Situations (CISS) and the SF-12 Health Survey (SF-12). A forward stepwise multiple regression analysis was used to ascertain those coping strategies significantly associated with participants' perceived health status. RESULTS: Complete documentation was received from 113 registered unemployed participants, (61 men and 52 women) giving a response rate of 45% .Physical health status was significantly and positively associated with age and task-oriented coping, while the perception of mental health was associated not only with age, but also by lower emotion-oriented coping and a low number of previous job losses. CONCLUSION: The perception of health status is reduced among unemployed. Age is the only socio demographic variable that influences the perception of health status. Adaptive Task-oriented coping strategies are related to better physical health perception, whereas Emotion-oriented coping makes people prone to poorer mental health perception. PMID- 26890725 TI - Association between work ability and fatigue in Brazilian nursing workers. AB - BACKGROUND: Impaired work ability is associated with work-related illnesses, early retirement and rising pension costs. OBJECTIVE: To investigate the association between work ability and fatigue in nursing workers. METHODS: Cross sectional study conducted with 100 nursing workers from two inpatient units at a public teaching hospital in Sao Paulo, Brazil. The data were collected by means of a socio-demographic profile questionnaire, Work Ability Index (WAI) and Chalder Fatigue Scale. The data were analyzed by means of descriptive and analytical statistical methods, tests of association and multiple linear regression. RESULTS: The study population was mainly composed of women (88% ), exhibited a high educational level (76% ), average age 39.4 years old (SD = 9.5) and 15 years of professional experience, on average. The average score on WAI was good (39.4 points, SD = 6.0) but surprisingly, 35% of the participants exhibited moderate to poor work ability. Fatigue was found in 52% of the participants. The score on WAI decreased in association with fatigue (p < 0.001) and longer length of work in the same workplace (p = 0.001), as well as among nursing technicians compared to nurses (p = 0.040). CONCLUSIONS: Fatigue, longer length of work in the same workplace and work category nursing technician were associated with decreased work ability, which emphasizes the need for investment in health and quality of work life. PMID- 26890726 TI - Assessment of hemostatic changes in a model of acute hemorrhage in dogs. AB - OBJECTIVE: To evaluate hemostatic changes following experimental acute hemorrhage in dogs using traditional coagulation tests (eg, platelet count, prothrombin time [PT], and activated partial thromboplastin time [aPTT]), kaolin-activated thromboelastography (TEG), and whole blood multiple electrode impedance platelet aggregometry. DESIGN: Prospective study. SETTING: Research laboratory. ANIMALS: Five Beagles. INTERVENTIONS: Dogs were anesthetized prior to obtaining blood samples for baseline PCV, total plasma protein (TPP), arterial blood-gas, platelet count, PT, aPTT, TEG, fibrinogen, and aggregometry. Blood was obtained at 4 additional time points, following 20% blood volume loss, 40% blood volume loss, 60 minutes of sustained hypotension, and after autologous blood transfusion. In addition, heart rate and direct arterial blood pressure were measured at each time point. MEASUREMENTS AND MAIN RESULTS: Significant decreases were noted for PCV (P = 0.048), TPP (P < 0.0001), and arterial blood pressures (P < 0.0001) over time. Platelet count did not change significantly (P = 0.879), but platelet function was decreased following hemorrhage when arachidonic acid (P = 0.004) and ADP (P = 0.008) were used as agonists. The TEG variables R (P = 0.030), MA (P = 0.043), and G (P = 0.037) were significantly, albeit mildly, changed following hemorrhage. Significant prolongations in PT (P < 0.0001) and aPTT (P = 0.041), and decreases in fibrinogen concentration (P = 0.002) were also seen. CONCLUSION: Platelet dysfunction occurred following hemorrhage in this model, despite a stable platelet count. Additionally, significant changes associated with hemorrhage were documented in aPTT, fibrinogen, and MA. Platelet function testing in dogs with naturally occurring hemorrhage warrants further investigation. PMID- 26890727 TI - Correction: Rich RNA Structure Landscapes Revealed by Mutate-and-Map Analysis. PMID- 26890729 TI - A Historical Perspective on the Development of the Allan Variances and Their Strengths and Weaknesses. AB - Over the past 50 years, variances have been developed for characterizing the instabilities of precision clocks and oscillators. These instabilities are often modeled as nonstationary processes, and the variances have been shown to be well behaved and to be unbiased, efficient descriptors of these types of processes. This paper presents a historical overview of the development of these variances. The time-domain and frequency-domain formulations are presented and their development is described. The strengths and weaknesses of these characterization metrics are discussed. These variances are also shown to be useful in other applications, such as in telecommunication. PMID- 26890731 TI - P Matrix Analysis of Surface Acoustic Waves in Piezoelectric Phononic Crystals. AB - Large time/memory costs have constituted a significant obstacle for accurately analyzing surface acoustic waves (SAWs) in large size two-dimensional (2-D) piezoelectric phononic crystals (PnCs). To overcome this obstacle, this study introduces the unit P matrix and its associated cascading. To obtain an accurate unit P matrix, the Y parameters of the SAW delay lines were derived using a three dimensional (3-D) finite element model (FEM) with and without 2-D piezoelectric PnCs, respectively, on the transmitting path. A time window function was adopted to extract the desired signals from the P matrix analysis. Then, unit P matrix cascading was used to obtain SAW propagation parameters for the large size piezoelectric PnCs. Using this method, the SAW in aluminum (Al) /128o-YXLiNbO3 PnCs was analyzed over 150 periods. Experiments were also conducted. To choose the appropriate size of the unit P matrix, the variance between experimental results and theoretical results, and time/memory cost were compared for different periods. The results indicate that cascading by unit P matrix of 25 PnCs periods can be appropriately adopted to accurately derive the SAW propagation parameters over 150 periods. This indicates the accuracy of the unit P matrix derived by 3-D FEM and the effectiveness of P matrix analysis. PMID- 26890728 TI - "Quantum Leap" in Photobiomodulation Therapy Ushers in a New Generation of Light Based Treatments for Cancer and Other Complex Diseases: Perspective and Mini Review. AB - OBJECTIVE: Set within the context of the 2015 International Year of Light and Light-Based Technologies,and of a growing and aging world population with ever rising healthcare needs, this perspective and mini-review focuses on photobiomodulation (PBM) therapy as an emerging, cost-effective, treatment option for cancer (i.e., solid tumors) and other complex diseases, particularly, of the eye (e.g., age-related macular degeneration, diabetic retinopathy, glaucoma, retinitis pigmentosa) and the central nervous system (e.g., Alzheimer's and Parkinson's disease). BACKGROUND DATA: Over the last decades, primary and secondary mechanisms of PBM have been revealed. These include oxygen-dependent and oxygen-independent structural and functional action pathways. Signal and target characteristics determine biological outcome, which is optimal (or even positive) only within a given set of parameters. METHODS: This study was a perspective and nonsystematic literature mini-review. RESULTS: Studies support what we describe as a paradigm shift or "quantum leap" in the understanding and use of light and its interaction with water and other relevant photo-cceptors to restore physiologic function. CONCLUSIONS: Based on existing evidence, it is argued that PBM therapy can raise the standard of care and improve the quality of life of patients for a fraction of the cost of many current approaches. PBM therapy can, therefore,benefit large, vulnerable population groups, including the elderly and the poor, whilehaving a major impact on medical practice and public finances. PMID- 26890730 TI - Ultrafast Harmonic Coherent Compound (UHCC) Imaging for High Frame Rate Echocardiography and Shear-Wave Elastography. AB - Transthoracic shear-wave elastography (SWE) of the myocardium remains very challenging due to the poor quality of transthoracic ultrafast imaging and the presence of clutter noise, jitter, phase aberration, and ultrasound reverberation. Several approaches, such as diverging-wave coherent compounding or focused harmonic imaging, have been proposed to improve the imaging quality. In this study, we introduce ultrafast harmonic coherent compounding (UHCC), in which pulse-inverted diverging waves are emitted and coherently compounded, and show that such an approach can be used to enhance both SWE and high frame rate (FR) B mode Imaging. UHCC SWE was first tested in phantoms containing an aberrating layer and was compared against pulse-inversion harmonic imaging and against ultrafast coherent compounding (UCC) imaging at the fundamental frequency. In vivo feasibility of the technique was then evaluated in six healthy volunteers by measuring myocardial stiffness during diastole in transthoracic imaging. We also demonstrated that improvements in imaging quality could be achieved using UHCC B mode imaging in healthy volunteers. The quality of transthoracic images of the heart was found to be improved with the number of pulse-inverted diverging waves with a reduction of the imaging mean clutter level up to 13.8 dB when compared against UCC at the fundamental frequency. These results demonstrated that UHCC B mode imaging is promising for imaging deep tissues exposed to aberration sources with a high FR. PMID- 26890732 TI - Targeted Lesion Generation Through the Skull Without Aberration Correction Using Histotripsy. AB - This study demonstrates the ability of histotripsy to generate targeted lesions through the skullcap without using aberration correction. Histotripsy therapy was delivered using a 500 kHz, 256-element hemispherical transducer with an aperture diameter of 30 cm and a focal distance of 15 cm fabricated in our lab. This transducer is theoretically capable of producing peak rarefactional pressures, based on linear estimation, (p-)LE, in the free field in excess of 200MPa with pulse durations 2 acoustic cycles. Three excised human skullcaps were used displaying attenuations of 73-81% of the acoustic pressure without aberration correction. Through all three skullcaps, compact lesions with radii less than 1mm were generated in red blood cell (RBC) agarose tissue phantoms without aberration correction, using estimated (p-)LE of 28-39MPa, a pulse repetition frequency of 1Hz, and a total number of 300 pulses. Lesion generation was consistently observed at the geometric focus of the transducer as the position of the skullcap with respect to the transducer was varied, and multiple patterned lesions were generated transcranially by mechanically adjusting the position of the skullcap with respect to the transducer to target different regions within. These results show that compact, targeted lesions with sharp boundaries can be generated through intact skullcaps using histotripsy with very short pulses without using aberration correction. Such capability has the potential to greatly simplify transcranial ultrasound therapy for non-invasive transcranial applications, as current ultrasound transcranial therapy techniques all require sophisticated aberration correction. PMID- 26890733 TI - Sex Differences in Hookah-Related Images Posted on Tumblr: A Content Analysis. AB - Hookah tobacco smoking is prevalent, widespread, and associated with large amounts of toxicants. Hookah tobacco smoking may be viewed differently by males and females. For example, females have been drawn to types of tobacco that are flavored, milder, and marketed as more social and exotic. Individuals often use the growing segment of anonymous social networking sites, such as Tumblr, to learn about potentially dangerous or harmful behaviors. We used a systematic process involving stratification by time of day, day of week, and search term to gather a sample of 140 Tumblr posts related to hookah tobacco smoking. After a structured codebook development process, 2 coders independently assessed all posts in their entirety, and all disagreements were easily adjudicated. When data on poster sex and age were available, we found that 77% of posts were posted by females and 35% were posted by individuals younger than 18. The most prominent features displayed in all posts were references to or images of hookahs themselves, sexuality, socializing, alcohol, hookah smoke, and tricks performed with hookah smoke. Compared with females, males more frequently posted images of hookahs and alcohol-related images or references. This information may help guide future research in this area and the development of targeted interventions to curb this behavior. PMID- 26890734 TI - Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study. AB - OBJECTIVE: In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger-causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls. METHODS: Twenty LTLE, 20 RTLE, and 20 healthy controls underwent a resting-state high-density EEG recording. Source activity was obtained for 82 regions of interest (ROIs) using an individual head model and a distributed linear inverse solution. Granger causal modeling was applied to the source signals of all ROIs. The directed functional connectivity results were compared between groups and correlated with clinical parameters (duration of the disease, age of onset, age, and learning and mood impairments). RESULTS: We found that: (1) patients had significantly reduced connectivity from regions concordant with the default-mode network; (2) there was a different network pattern in patients versus controls: the strongest connections arose from the ipsilateral hippocampus in patients and from the posterior cingulate cortex in controls; (3) longer disease duration was associated with lower driving from contralateral and ipsilateral mediolimbic regions in RTLE; (4) aging was associated with a lower driving from regions in or close to the piriform cortex only in patients; and (5) outflow from the anterior cingulate cortex was lower in patients with learning deficits or depression compared to patients without impairments and to controls. SIGNIFICANCE: Resting state network reorganization in the absence of IEDs strengthens the view of chronic and progressive network changes in TLE. These resting-state connectivity alterations could constitute an important biomarker of TLE, and hold promise for using EEG recordings without IEDs for diagnosis or prognosis of this disorder. PMID- 26890735 TI - The Disconnection Hypothesis in Alzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging. AB - According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group. PMID- 26890737 TI - Puerarin Ameliorates D-Galactose Induced Enhanced Hippocampal Neurogenesis and Tau Hyperphosphorylation in Rat Brain. AB - Enhanced neurogenesis has been reported in the hippocampus of patients with Alzheimer's disease (AD), the most common neurodegenerative disorder characterized with amyloid-beta (Abeta) aggregation, tau hyperphosphorylation, and progressive neuronal loss. Previously we reported that tau phosphorylation played an essential role in adult hippocampal neurogenesis, and activation of glycogen synthase kinase (GSK-3), a crucial tau kinase, could induce increased hippocampal neurogenesis. In the present study, we found that treatment of D galactose rats with Puerarin could significantly improve behavioral performance and ameliorate the enhanced neurogenesis and microtubule-associated protein tau hyperphosphorylation in the hippocampus of D-galactose rat brains. FGF-2/GSK-3 signaling pathway might be involved in the effects of Puerarin on hippocampal neurogenesis and tau hyperphosphorylation. Our finding provides primary in vivo evidence that Puerarin can attenuate AD-like enhanced hippocampal neurogenesis and tau hyperphosphorylation. Our finding also suggests Puerarin can be served as a treatment for age-related neurodegenerative disorders, such as AD. PMID- 26890738 TI - A TgCRND8 Mouse Model of Alzheimer's Disease Exhibits Sexual Dimorphisms in Behavioral Indices of Cognitive Reserve. AB - Cognitive decline is sexually dimorphic in Alzheimer's disease (AD). Men show higher incidences of amnestic mild cognitive impairment yet women disproportionally phenoconvert to AD. It is hypothesized that men maintain greater cognitive reserve than women under comparable amyloid-beta (Abeta) challenge. One behavioral aspect of cognitive reserve in mice is the capacity to cope with Abeta-associated stereotypies by switching to increasingly effective navigational search strategies in the Morris water maze. To explore inherent sex differences in this paradigm, however, we require an AbetaPP mouse model wherein behavioral flexibility is impaired earlier in females than males despite equivalent Abeta load. Here, we show that when F1 C57Bl/6*C3H/HeJ TgCRND8 mice are placed on C57Bl/6 background, N5 Tg males and females exhibit equivalent Abeta pathologies at 2, 4, 6, and 8 months of age yet females display learning and memory deficits earlier than males. We further show that this N5 line does not carry the autosomal recessive pde6brd1 mutation that impairs visual acuity and that the estrous cycle is not disrupted on this genetic background. At 5.5 months of age, Tg males, but not females, compensate for Abeta-associated stereotypic behaviors (i.e., hyperactive tight circling) by alternating navigational search strategies and adopting increasingly productive spatial search strategies. Females fail to overcome Abeta-associated stereotypies and do not efficiently switch from systematic to spatial learning strategies. Together, these data identify a novel AbetaPP mouse model that can be used for preclinical testing of interventions targeting sexual dimorphisms in behavioral indices of cognitive reserve. PMID- 26890739 TI - A History of In Vivo Neutron Activation Analysis in Measurement of Aluminum in Human Subjects. AB - Aluminum, as an abundant metal, has gained widespread use in human life, entering the body predominantly as an additive to various foods and drinking water. Other major sources of exposure to aluminum include medical, cosmetic, and occupational routes. As a common environmental toxin, with well-known roles in several medical conditions such as dialysis encephalopathy, aluminum is considered a potential candidate in the causality of Alzheimer's disease. Aluminum mostly accumulates in the bone, which makes bone an indicator of the body burden of aluminum and an ideal organ as a proxy for the brain. Most of the techniques developed for measuring aluminum include bone biopsy, which requires invasive measures, causing inconvenience for the patients. There has been a considerable effort in developing non-invasive approaches, which allow for monitoring aluminum levels for medical and occupational purposes in larger populations. In vivo neutron activation analysis, a method based on nuclear activation of isotopes of elements in the body and their subsequent detection, has proven to be an invaluable tool for this purpose. There are definite challenges in developing in vivo non invasive techniques capable of detecting low levels of aluminum in healthy individuals and aluminum-exposed populations. The following review examines the method of in vivo neutron activation analysis in the context of aluminum measurement in humans focusing on different neutron sources, interference from other activation products, and the improvements made in minimum detectable limits and patient dose over the past few decades. PMID- 26890736 TI - Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial. AB - Diabetes and hyperinsulinemia may be risk factors for Alzheimer's disease (AD). We conducted a pilot study of metformin, a medication efficacious in treating and preventing diabetes while reducing hyperinsulinemia, among persons with amnestic mild cognitive impairment (aMCI) with the goal of collecting preliminary data on feasibility, safety, and efficacy. Participants were 80 men and women aged 55 to 90 years with aMCI, overweight or obese, without treated diabetes. We randomized participants to metformin 1000 mg twice a day or matching placebo for 12 months. The co-primary clinical outcomes were changes from baseline to 12 months in total recall of the Selective Reminding Test (SRT) and the score of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). The secondary outcome was change in relative glucose uptake in the posterior cingulate-precuneus in brain fluorodeoxyglucose positron emission tomography. Change in plasma Abeta42 was an exploratory outcome. The mean age of participants was 65 years. Fifty percent of participants were women. The only baseline variable that was different between the arms was the ADAS-Cog. Metformin could not be tolerated by 7.5% of participants; 15% tolerated 500 mg/day, 35% tolerated 1000 mg/day, 32.5% tolerated 1500 mg/day, and only 10% tolerated the maximum dose. There were no serious adverse events related to metformin. The 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms. After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group (9.7+/-8.5 versus 5.3+/-8.5; p = 0.02). Differences for other outcomes were not significant. A larger trial seems warranted to evaluate the efficacy and cognitive safety of metformin in prodromal AD. PMID- 26890740 TI - Impact of Depressive Symptoms on Conversion from Mild Cognitive Impairment Subtypes to Alzheimer's Disease: A Community-Based Longitudinal Study. AB - BACKGROUND: While longitudinal studies have investigated the relationships between mild cognitive impairment (MCI) subtypes and dementia subtypes, the results have been contradictory. In addition, some research shows that depression accompanied by MCI might increase the risk of Alzheimer's disease (AD). OBJECTIVE: The aim of this study is to longitudinally investigate the relationships between MCI subtypes and dementia subtypes, with special attention to the effect of comorbid depressive symptoms in a Japanese rural community. METHODS: Non-demented participants (n = 802) completed a baseline and follow-up study. Outcomes were conversion to dementia especially AD, MCI, or no conversion. A complementary log-log analysis was conducted to investigate the risk of dementia and AD in amnestic MCI (aMCI) compared to nonamnestic MCI (naMCI) groups. The impact of depressive symptoms on the transition from MCI to AD and from cognitively normal to MCI or AD was also analyzed. RESULTS: The risk of developing dementia, in particular AD, for the aMCI group was significantly higher than that for the naMCI group. In the aMCI group, the presence of depressive symptoms increased the risk of developing AD, but depressive symptoms in the naMCI group did not. In the cognitively normal group, the presence of depressive symptoms increased the risk of aMCI but not naMCI or AD. CONCLUSION: MCI subtyping could be useful in finding a prodrome for dementia and in particular for AD. The differing impacts of depressive symptoms on the development of AD suggest that the relationship between depressive symptoms and cognitive impairment could differ in aMCI and naMCI patients. PMID- 26890741 TI - Vascular Risk Factors and Cognition in Parkinson's Disease. AB - Vascular risk factors have been associated with cognitive deficits and incident dementia in the general population, but their role on cognitive dysfunction in Parkinson's disease (PD) is still unclear. The present study addresses the single and cumulative effect of vascular risk factors on cognition in PD patients, taking clinical confounders into account. Standardized neuropsychological assessment was performed in 238 consecutive PD patients. We evaluated the association of single and cumulative vascular risk factors (smoking, diabetes, hypercholesterolemia, hypertension, and heart disease), with the diagnosis of PD normal cognition (PDNC, n = 94), mild cognitive impairment (PD-MCI, n = 111), and dementia (PDD, n = 33). The association between single neuropsychological tests and vascular risk factors was evaluated with covariance analyses adjusted for age at onset, educational levels, gender, disease duration, and motor performance. Age, educational levels, disease duration, and motor function were significantly different between PDNC, PD-MCI, and PDD. Heart disease was the only vascular factor significantly more prevalent in PDD compared with PDNC in adjusted analyses. Performance of tests assessing executive and attention functions were significantly worse in patients with hypertension, heart disease, and/or diabetes (p < 0.05). Heart disease is associated with dementia in PD, suggesting a potential window of intervention. Vascular risk factors act especially on attention and executive functions in PD. Vascular risk stratification may be useful in order to identify PD patients with a greater risk of developing dementia. These findings need to be verified in longitudinal studies. PMID- 26890743 TI - Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks. AB - Although the incidence of Alzheimer's disease (AD) is continuously increasing in the aging population worldwide, effective therapies are not available. The interplay between causative genetic and environmental factors is partially understood. Meta-analyses have been performed on aspects such as polymorphisms, cytokines, and cognitive training. Here, we propose a meta-analysis approach based on hierarchical clustering analysis of a reliable training set of hippocampus biopsies, which is condensed to a gene expression signature. This gene expression signature was applied to various test sets of brain biopsies and iPSC-derived neuronal cell models to demonstrate its ability to distinguish AD samples from control. Thus, our identified AD-gene signature may form the basis for determination of biomarkers that are urgently needed to overcome current diagnostic shortfalls. Intriguingly, the well-described AD-related genes APP and APOE are not within the signature because their gene expression profiles show a lower correlation to the disease phenotype than genes from the signature. This is in line with the differing characteristics of the disease as early-/late-onset or with/without genetic predisposition. To investigate the gene signature's systemic role(s), signaling pathways, gene ontologies, and transcription factors were analyzed which revealed over-representation of response to stress, regulation of cellular metabolic processes, and reactive oxygen species. Additionally, our results clearly point to an important role of FOXA1 and FOXA2 gene regulatory networks in the etiology of AD. This finding is in corroboration with the recently reported major role of the dopaminergic system in the development of AD and its regulation by FOXA1 and FOXA2. PMID- 26890742 TI - A Mercaptoacetamide-Based Class II Histone Deacetylase Inhibitor Increases Dendritic Spine Density via RasGRF1/ERK Pathway. AB - BACKGROUND: The accumulation of amyloid-beta (Abeta) leads to the loss of dendritic spines and synapses, which is hypothesized to cause cognitive impairments in Alzheimer's disease (AD) patients. In our previous study, we demonstrated that a novel mercaptoacetamide-based class II histone deacetylase inhibitor (HDACI), known as W2, decreased Abeta levels and improved learning and memory in mice. However, the underlying mechanism of this effect is unknown. OBJECTIVE: Because dendritic spine formation is associated with cognitive performance, here we investigated whether HDACI W2 regulates dendritic spine density and its molecular mechanism of action. METHODS: To examine the effect of HDACI W2 on dendritic spine density, we conducted morphological analysis of dendritic spines using GFP transfection and Golgi staining. In addition, to determine the molecular mechanism of W2 effects on spines, we measured the levels of mRNAs and proteins involved in the Ras signaling pathway using quantitative real-time PCR, immunocytochemistry, and western analysis. RESULTS: We found that HDACI W2 altered dendritic spine density and morphology in vitro and in vivo. Additionally, W2 increased the mRNA or protein levels of Ras GRF1 and phospho ERK. Moreover, knockdown of RasGRF1 and inhibition of ERK activity prevented the W2-mediated spinogenesis in primary hippocampal neurons. CONCLUSION: Our Class II selective HDACI W2 promotes the formation and growth of dendritic spines in a RasGRF1 and ERK dependent manner in primary hippocampal neurons. PMID- 26890744 TI - miR-302 Attenuates Amyloid-beta-Induced Neurotoxicity through Activation of Akt Signaling. AB - Deficiency of insulin signaling has been linked to diabetes and ageing-related neurodegenerative diseases such as Alzheimer's disease (AD). In this regard, brains exhibit defective insulin receptor substrate-1 (IRS-1) and hence result in alteration of insulin signaling in progression of AD, the most common cause of dementia. Consequently, dysregulation of insulin signaling plays an important role in amyloid-beta (Abeta)-induced neurotoxicity. As the derivation of induced pluripotent stem cells (iPSC) involves cell reprogramming, it may provide a means for regaining the control of ageing-associated dysfunction and neurodegeneration via affecting insulin-related signaling. To this, we found that an embryonic stem cell (ESC)-specific microRNA, miR-302, silences phosphatase and tensin homolog (PTEN) to activate Akt signaling, which subsequently stimulates nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) elevation and hence inhibits Abeta-induced neurotoxicity. miR-302 is predominantly expressed in iPSCs and is known to regulate several important biological processes of anti-oxidative stress, anti-apoptosis, and anti-aging through activating Akt signaling. In addition, we also found that miR-302-mediated Akt signaling further stimulates Nanog expression to suppress Abeta-induced p-Ser307 IRS-1 expression and thus enhances tyrosine phosphorylation and p-Ser 473-Akt/p-Ser 9-GSK3beta formation. Furthermore, our in vivo studies revealed that the mRNA expression levels of both Nanog and miR-302-encoding LARP7 genes were significantly reduced in AD patients' blood cells, providing a novel diagnosis marker for AD. Taken together, our findings demonstrated that miR-302 is able to inhibit Abeta-induced cytotoxicity via activating Akt signaling to upregulate Nrf2 and Nanog expressions, leading to a marked restoration of insulin signaling in AD neurons. PMID- 26890745 TI - Non-Verbal Episodic Memory Deficits in Primary Progressive Aphasias are Highly Predictive of Underlying Amyloid Pathology. AB - Diagnostic distinction of primary progressive aphasias (PPA) remains challenging, in particular for the logopenic (lvPPA) and nonfluent/agrammatic (naPPA) variants. Recent findings highlight that episodic memory deficits appear to discriminate these PPA variants from each other, as only lvPPA perform poorly on these tasks while having underlying amyloid pathology similar to that seen in amnestic dementias like Alzheimer's disease (AD). Most memory tests are, however, language based and thus potentially confounded by the prevalent language deficits in PPA. The current study investigated this issue across PPA variants by contrasting verbal and non-verbal episodic memory measures while controlling for their performance on a language subtest of a general cognitive screen. A total of 203 participants were included (25 lvPPA; 29 naPPA; 59 AD; 90 controls) and underwent extensive verbal and non-verbal episodic memory testing, with a subset of patients (n = 45) with confirmed amyloid profiles as assessed by Pittsburgh Compound B and PET. The most powerful discriminator between naPPA and lvPPA patients was a non-verbal recall measure (Rey Complex Figure delayed recall), with 81% of PPA patients classified correctly at presentation. Importantly, AD and lvPPA patients performed comparably on this measure, further highlighting the importance of underlying amyloid pathology in episodic memory profiles. The findings demonstrate that non-verbal recall emerges as the best discriminator of lvPPA and naPPA when controlling for language deficits in high load amyloid PPA cases. PMID- 26890747 TI - Anthocyanins Protect SK-N-SH Cells Against Acrolein-Induced Toxicity by Preserving the Cellular Redox State. AB - In Alzheimer's disease (AD) and in mild cognitive impairment (MCI) patients, by products of lipid peroxidation such as acrolein accumulated in vulnerable regions of the brain. We have previously shown that acrolein is a highly reactive and neurotoxic aldehyde and its toxicity involves the alteration of several redox sensitive pathways. Recently, protein-conjugated acrolein in cerebrospinal fluid has been proposed as a biomarker to distinguish between MCI and AD. With growing evidence of the early involvement of oxidative stress in AD etiology, one would expect that a successful therapy should prevent brain oxidative damage. In this regard, several studies have demonstrated that polyphenol-rich extracts exert beneficial effect on cognitive impairment and oxidative stress. We have recently demonstrated the efficacy of an anthocyanin formulation (MAF14001) against amyloid-beta-induced oxidative stress. The aim of this study is to investigate the neuroprotective effect of MAF14001 as a mixture of anthocyanins, a particular class of polyphenols, against acrolein-induced oxidative damage in SK-N-SH neuronal cells. Our results demonstrated that MAF14001, from 5MUM, was able to efficiently protect SK-N-SH cells against acrolein-induced cell death. MAF14001 was able to lower reactive oxygen species and protein carbonyl levels induced by acrolein. Moreover, MAF1401 prevented glutathione depletion and positively modulated, in the presence of acrolein, some oxidative stress-sensitive pathways including the transcription factors NF-kappaB and Nrf2, the proteins gamma-GCS and GSK3beta, and the protein adaptator p66Shc. Along with its proven protective effect against amyloid-beta toxicity, these results demonstrate that MAF14001 could target multiple mechanisms and could be a promising agent for AD prevention. PMID- 26890748 TI - Iron Regulates Apolipoprotein E Expression and Secretion in Neurons and Astrocytes. AB - BACKGROUND: There is strong evidence that iron homeostasis is impaired in the aging and Alzheimer's disease (AD) brain and that this contributes to neurodegeneration. Apolipoprotein E (APOE) has been identified as the strongest genetic risk factor for AD. However, the interaction between the two has yet to be fully explored. OBJECTIVE: This study aimed to investigate the relationship between exogenous iron levels and ApoE in neurons and astrocytes. METHODS: Our study used primary cultured cortical neurons and astrocytes to investigate the changes in ApoE caused by iron. Western blot and RT-PCR were used to measure ApoE. RESULTS: We observed that iron upregulated intracellular ApoE levels in both neurons and astrocytes at the post-transcriptional and transcriptional level, respectively. However, there was less full-length ApoE secreted by neurons and astrocytes after iron treatment. We speculate that this might impair brain lipid metabolism and amyloid-beta clearance. In terms of ApoE receptors, we observed that neuronal LRP-1 levels were increased by the addition of exogenous iron, which could contribute to AbetaPP endocytosis in neurons. However, there were no significant changes in neuronal LDLR, astrocyte LDLR, or astrocyte LRP-1. CONCLUSION: Our study reveals that iron may contribute to the pathogenesis of AD by affecting ApoE and its receptors and supports the notion that iron chelation should be investigated as a therapeutic strategy for AD. PMID- 26890746 TI - STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-beta Toxicity. AB - Because STX is a selective ligand for membrane estrogen receptors, it may be able to confer the beneficial effects of estrogen without eliciting the deleterious side effects associated with activation of the nuclear estrogen receptors. This study evaluates the neuroprotective properties of STX in the context of amyloid beta (Abeta) exposure. MC65 and SH-SY5Y neuroblastoma cell lines, as well as primary hippocampal neurons from wild type (WT) and Tg2576 mice, were used to investigate the ability of STX to attenuate cell death, mitochondrial dysfunction, dendritic simplification, and synaptic loss induced by Abeta. STX prevented Abeta-induced cell death in both neuroblastoma cell lines; it also normalized the decrease in ATP and mitochondrial gene expression caused by Abeta in these cells. Notably, STX also increased ATP content and mitochondrial gene expression in control neuroblastoma cells (in the absence of Abeta). Likewise in primary neurons, STX increased ATP levels and mitochondrial gene expression in both genotypes. In addition, STX treatment enhanced dendritic arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites caused by Abeta exposure in Tg2576 neurons. These data suggest that STX can act as an effective neuroprotective agent in the context of Abeta toxicity, improving mitochondrial function as well as dendritic growth and synaptic differentiation. In addition, since STX also improved these endpoints in the absence of Abeta, this compound may have broader therapeutic value beyond Alzheimer's disease. PMID- 26890749 TI - Longitudinal Memory Profiles in Behavioral-Variant Frontotemporal Dementia and Alzheimer's Disease. AB - BACKGROUND: Alzheimer's disease (AD) and behavioral-variant of frontotemporal dementia (bvFTD) can present with an overlapping neuropsychological profile, which often hinders their clinical differentiation. OBJECTIVE: To compare changes over time in memory, general cognition tasks, and functional scales between bvFTD and AD. METHODS: Consecutive cases diagnosed with probable bvFTD (n = 22) and typical AD (n = 31) with at least two clinical visits were selected. Of these, 13 (9 AD, 4 bvFTD) underwent Pittsburgh compound B PET scan, which supported the clinical diagnosis in all cases. Mixed-model regressions were used to estimate the differential rate of decline on selected tasks between cohorts. RESULTS: Analyses demonstrated that, despite equivalent baseline performance, bvFTD patients experienced a more rapid functional deterioration and a steeper decline in global cognition than AD patients. At baseline, both groups were impaired on executive function and memory tasks compared to controls, but these deficits were more marked in the bvFTD group. In addition, performance on these domains continued to decline more rapidly in this group. CONCLUSIONS: Neither the initial neuropsychological assessment nor projected performances can reliably distinguish the totality of bvFTD and AD individuals. Nevertheless, annual rates of progression on cognitive tasks provide valuable information and will potentially help establish the impact of future therapeutic treatments in these dementia syndromes. PMID- 26890750 TI - Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory. AB - Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases. PMID- 26890751 TI - Heterogeneous Language Profiles in Patients with Primary Progressive Aphasia due to Alzheimer's Disease. AB - BACKGROUND: The logopenic variant of Primary Progressive Aphasia (lvPPA) is associated with underlying Alzheimer's disease (AD) pathology and characterized by impaired single word retrieval and repetition of phrases and sentences. OBJECTIVE: We set out to study whether logopenic aphasia is indeed the prototypic language profile in PPA patients with biomarker evidence of underlying AD pathology and to correlate language profiles with cortical atrophy patterns on MRI. METHODS: Inclusion criteria: (I) clinical diagnosis of PPA; (II) CSF profile and/or PiB-PET scan indicative for amyloid pathology; (III) availability of expert language evaluation. Based on language evaluation, patients were classified as lvPPA (fulfilling lvPPA core criteria), lvPPA extended (fulfilling core criteria plus other language disturbances), or PPA unclassifiable (not fulfilling lvPPA core criteria). Cortical atrophy patterns on MRI were visually rated and quantitative measurements of cortical thickness were performed using FreeSurfer. RESULTS: We included 22 patients (age 67+/-7 years, 50% female, MMSE 21+/-6). 41% were classified as lvPPA, 36% as lvPPA extended with additional deficits in language comprehension and/or confrontation naming, and 23% as PPA unclassifiable. By both qualitative and quantitative measurements, patients with lvPPA showed mild global cortical atrophy on MRI, whereas patients with lvPPA extended showed more focal cortical atrophy, predominantly at the left tempo parietal side. For PPA unclassifiable, qualitative measurements revealed a heterogeneous atrophy pattern. CONCLUSION: Although most patients fulfilled the lvPPA criteria, we found that their language profiles were heterogeneous. The clinical and radiological spectrum of PPA due to underlying AD pathology is broader than pure lvPPA. PMID- 26890752 TI - Late-Onset Metachromatic Leukodystrophy with Early Onset Dementia Associated with a Novel Missense Mutation in the Arylsulfatase A Gene. AB - A 48-year-old male patient presented with personality changes and progressive memory loss over 2 years with initially suspected Hashimoto's encephalopathy. Strategy of diagnostic workup of early onset dementia included dementia from neurodegenerative, neuroinflammatory, metabolic/toxic, and psychiatric origin. The patient's neurological exam was normal. MRI revealed a leukencephalopathy, predominantly in the frontal periventricular white matter, without notable changes over 2 years. On neurophysiological examination, prolonged central conduction times and a sensorimotor polyneuropathy were noted. Neuropsychological impairment included disorientation in place and a reduced short time memory. Behavioral alterations were predominated by sudden mood changes and disinhibition. Cerebrospinal fluid was normal. Despite presence of thyroid autoantibodies, glucocorticosteroid treatment did not improve the dementia. A metachromatic leukodystrophy was diagnosed by decreased arylsulfatase-A activity in leucocytes/fibroblasts and identification of a compound heterozygous mutation in the ARSA gene: c.542T>G (exon 3) and the novel mutation c.1013T>C (exon 6). Pathogenic function was suggested by bioinformatic mutation search. In a patient with early onset dementia, strategic diagnostic workup including genetic assessment revealed an adult-onset metachromatic leukodystrophy with a novel mutation in the arylsulfatase A gene. PMID- 26890754 TI - Health-Related Quality of Life in Patients with Alzheimer's Disease in Different German Health Care Settings. AB - The purpose of this study is to evaluate the health-related quality of life (HrQoL) of patients with Alzheimer's disease (AD) in different care settings (institutionalized versus community-dwelling) across all severity stages of dementia. Patients were consecutively recruited with their primary caregivers (123 inpatients and 272 outpatients), and the impact of patient-related parameters such as behavioral and psychological symptoms of dementia (BPSD) (Geriatric Depression Scale [GDS] and Neuropsychiatric Inventory [NPI]) and functional capacity (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]) on HrQoL was analyzed. Patients' HrQoL was assessed using self reported and caregiver-rated generic (EuroQoL Instrument) and dementia-specific (Quality of Life-Alzheimer's Disease [Qol-AD]) scales. Patients reported a considerably higher HrQoL than their caregivers on the QoL-AD, EQ-5D, and EQ VAS (p < 0.001). Different dementia severity groups showed significantly worse results in HrQoL for patients with lower MMSE scores. The mean self-reported QoL AD decreased from 32.3+/-5.7 in the group with the highest MMSE scores to 27.1+/ 5.5 in patients with the lowest MMSE scores (p < 0.001). A considerably lower HrQoL was shown for institutionalized patients versus participants in outpatient settings (proxy-rated QoL-AD 19.7+/-4.6 versus 26.0+/-7.1, p < 0.001). Depressive symptoms (GDS), BPSD (NPI), and reduced functional capacity (ADCS-ADL) were evaluated for their impact on patients' HrQoL. Multivariate models explained between 22% and 54% of the variance in patients' HrQoL. To analyze the causative direction of the reported associations, further longitudinal studies should be conducted. PMID- 26890753 TI - AZD3293: A Novel, Orally Active BACE1 Inhibitor with High Potency and Permeability and Markedly Slow Off-Rate Kinetics. AB - A growing body of pathological, biomarker, genetic, and mechanistic data suggests that amyloid accumulation, as a result of changes in production, processing, and/or clearance of brain amyloid-beta peptide (Abeta) concentrations, plays a key role in the pathogenesis of Alzheimer's disease (AD). Beta-secretase 1 (BACE1) mediates the first step in the processing of amyloid-beta protein precursor (AbetaPP) to Abeta peptides, with the soluble N terminal fragment of AbetaPP (sAbetaPPbeta) as a direct product, and BACE1 inhibition is an attractive target for therapeutic intervention to reduce the production of Abeta. Here, we report the in vitro and in vivo pharmacological profile of AZD3293, a potent, highly permeable, orally active, blood-brain barrier (BBB) penetrating, BACE1 inhibitor with unique slow off-rate kinetics. The in vitro potency of AZD3293 was demonstrated in several cellular models, including primary cortical neurons. In vivo in mice, guinea pigs, and dogs, AZD3293 displayed significant dose- and time dependent reductions in plasma, cerebrospinal fluid, and brain concentrations of Abeta40, Abeta42, and sAbetaPPbeta. The in vitro potency of AZD3293 in mouse and guinea pig primary cortical neuronal cells was correlated to the in vivo potency expressed as free AZD3293 concentrations in mouse and guinea pig brains. In mice and dogs, the slow off-rate from BACE1 may have translated into a prolongation of the observed effect beyond the turnover rate of Abeta. The preclinical data strongly support the clinical development of AZD3293, and patients with AD are currently being recruited into a combined Phase 2/3 study to test the disease modifying properties of AZD3293. PMID- 26890755 TI - Inhibition of Histone Deacetylase 3 Restores Amyloid-beta Oligomer-Induced Plasticity Deficit in Hippocampal CA1 Pyramidal Neurons. AB - Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with alterations in epigenetic factors leading to cognitive decline. Histone deacetylase 3 (HDAC3) is a known critical epigenetic negative regulator of learning and memory. In this study, attenuation of long-term potentiation by amyloid-beta oligomer, and its reversal by specific HDAC3 inhibitor RGFP966, was performed in rat CA1 pyramidal neurons using whole cell voltage-clamp and field recording techniques. Our findings provide the first evidence that amyloid-beta oligomer-induced synaptic plasticity impairment can be prevented by inhibition of HDAC3 enzyme both at the single neuron as well as in a population of neurons, thus identifying HDAC3 as a potential target for ameliorating AD related plasticity impairments. PMID- 26890757 TI - Performance on Specific Cognitive Domains and Cause of Death: A Prospective Population-Based Study in Non-Demented Older Adults (NEDICES). AB - Evidence regarding the relationship between performance on specific cognitive domains and cause of death is scarce. We assessed whether specific cognitive domains predicted mortality and the presence of any association with specific causes of death in a population-dwelling sample of non-demented older adults. In this population-based, prospective study (NEDICES), 2,390 non-demented subjects >=65 years completed a brief neuropsychological battery. Cox's proportional hazards models, adjusted by sociodemographic and comorbidity factors, global cognitive performance, educational level, and premorbid intelligence were used to assess the risk of death. Participants were followed for a median of 9.2 years (range 0.01-10.7), after which the death certificates of those who died were examined. 880 (36.8%) of 2,390 participants died over a median follow-up of 5.5 years (range 0.01-10.5). Using adjusted Cox regression models, we found that hazard ratios for mortality in participants within the lowest tertiles (worse performance) were 1.31 (speed of cognitive processing, p = 0.03); 1.22 (semantic fluency, p = 0.04), 1.32 (delayed free recall, p = 0.003), and 1.23 (delayed logical memory, p = 0.03). Poor performance on delayed recall and speed of cognitive processing tests were associated with dementia and cerebrovascular disease mortality, respectively. Further, poor performance on semantic fluency was associated with decreased cancer mortality. In this study of community dwelling non-demented older adults, worse neuropsychological performance was associated with increased risk of mortality. Performance on specific cognitive domains were related to different causes of death. Of particular note there appears to be an inverse association between poor semantic fluency and cancer mortality. PMID- 26890756 TI - The Presence of Select Tau Species in Human Peripheral Tissues and Their Relation to Alzheimer's Disease. AB - Tau becomes excessively phosphorylated in Alzheimer's disease (AD) and is widely studied within the brain. Further examination of the extent and types of tau present in peripheral tissues and their relation to AD is warranted given recent publications on pathologic spreading. Cases were selected based on the presence of pathological tau spinal cord deposits (n = 18). Tissue samples from sigmoid colon, scalp, abdominal skin, liver, and submandibular gland were analyzed by western blot and enzyme-linked immunosorbent assays (ELISAs) for certain tau species; frontal cortex gray matter was used for comparison. ELISAs revealed brain to have the highest total tau levels, followed by submandibular gland, sigmoid colon, liver, scalp, and abdominal skin. Western blots with antibodies recognizing tau phosphorylated at threonine 231(pT231), serine 396 and 404 (PHF 1), and an unmodified total human tau between residues 159 and 163 (HT7) revealed multiple banding patterns, some of which predominated in peripheral tissues. As submandibular gland had the highest levels of peripheral tau, a second set of submandibular gland samples were analyzed (n = 36; 19 AD, 17 non-demented controls). ELISAs revealed significantly lower levels of pS396 (p = 0.009) and pT231 (p = 0.005) in AD cases but not total tau (p = 0.18). Furthermore, pT231 levels in submandibular gland inversely correlated with Braak neurofibrillary tangle stage (p = 0.04), after adjusting for age at death, gender, and postmortem interval. These results provide evidence that certain tau species are present in peripheral tissues. Of potential importance, submandibular gland pT231 is progressively less abundant with increasing Braak neurofibrillary tangle stage. PMID- 26890758 TI - Screening for Mild Cognitive Impairment: Comparison of "MCI Specific" Screening Instruments. AB - BACKGROUND: Sensitive and specific instruments are required to screen for cognitive impairment (CI) in busy clinical practice. The Montreal Cognitive Assessment (MoCA) is widely validated but few studies compare it to tests designed specifically to detect mild cognitive impairment (MCI). OBJECTIVE: Comparison of two "MCI specific" screens: the Quick Mild Cognitive Impairment screen (Qmci) and MoCA. METHODS: Patients with subjective memory complaints (SMC; n = 73), MCI (n = 103), or dementia (n = 274), were referred to a university hospital memory clinic and underwent comprehensive assessment. Caregivers, without cognitive symptoms, were recruited as normal controls (n = 101). RESULTS: The Qmci was more accurate than the MoCA in differentiating MCI from controls, area under the curve (AUC) of 0.90 versus 0.80, p = 0.009. The Qmci had greater (AUC 0.81), albeit non-significant, accuracy than the MoCA (AUC 0.73) in separating MCI from SMC, p = 0.09. At its recommended cut-off (<62/100), the Qmci had a sensitivity of 90% and specificity of 87% for CI (MCI/dementia). Raising the cut-off to <65 optimized sensitivity (94%), reducing specificity (80%). At <26/30 the MoCA had better sensitivity (96%) but poor specificity (58%). A MoCA cut-off of <24 provided the optimal balance. Median Qmci administration time was 4.5 (+/-1.3) minutes compared with 9.5 (+/-2.8) for the MoCA. CONCLUSIONS: Although both tests distinguish MCI from dementia, the Qmci is particularly accurate in separating MCI from normal cognition and has shorter administration times, suggesting it is more useful in busy hospital clinics. This study reaffirms the high sensitivity of the MoCA but suggests a lower cut-off (<24) in this setting. PMID- 26890759 TI - Impact of Omega-3 Fatty Acid Supplementation on Memory Functions in Healthy Older Adults. AB - As the process of Alzheimer's disease (AD) begins years before disease onset, searching for prevention strategies is of major medical and economic importance. Nutritional supplementation with long-chain polyunsaturated omega-3 fatty acids (LC-n3-FA) may exert beneficial effects on brain structure and function. However, experimental evidence in older adults without clinical dementia is inconsistent, possibly due to low sensitivity of previously employed test batteries for detecting subtle improvements in cognition in healthy individuals. Here we used LOCATO, recently described as a robust and sensitive tool for assessing object location memory (OLM) in older adults, to evaluate the impact of LC-n3-FA supplementation on learning and memory formation. In a double-blind placebo controlled proof-of-concept study, 44 (20 female) cognitively healthy individuals aged 50-75 years received either LC-n3-FA (2,200 mg/day, n = 22) or placebo (n = 22) for 26 weeks. Before and after intervention, memory performance in the OLM task (primary) was tested. As secondary outcome parameters, performance in Rey Auditory Verbal Learning Test (AVLT), dietary habits, omega-3-index, and other blood-derived parameters were assessed. Omega-3 index increased significantly in the LC-n3-FA group compared with the placebo group. Moreover, recall of object locations was significantly better after LC-n3-FA supplementation compared with placebo. Performance in the AVLT was not significantly affected by LC-n3-FA. This double-blind placebo-controlled proof-of-concept study provides further experimental evidence that LC-n3-FA exert positive effects on memory functions in healthy older adults. Our findings suggest novel strategies to maintain cognitive functions into old age. PMID- 26890761 TI - Differential Membrane Toxicity of Amyloid-beta Fragments by Pore Forming Mechanisms. AB - A major characteristic of Alzheimer's disease (AD) is the presence of amyloid beta peptide (Abeta) oligomers and aggregates in the brain. It is known that Abeta oligomers interact with the neuronal membrane and induce perforations that cause an influx of calcium ions and enhance the release of synaptic vesicles leading to a delayed synaptic failure by vesicle depletion. To better understand the mechanism by which Abeta exerts its effect on the plasma membrane, we evaluated three Abeta fragments derived from different regions of Abeta(1-42); Abeta(1-28) from the N-terminal region, Abeta(25-35) from the central region, and Abeta(17-42) from the C-terminal region. The neuronal activities of these fragments were examined with patch clamp, immunofluorescence, transmission electron microscopy, aggregation assays, calcium imaging, and MTT reduction assays. The present results indicate that the fragment Abeta(1-28) contributes to aggregation, an increase in intracellular calcium and synaptotoxicity, but is not involved in membrane perforation; Abeta(25-35) is important for membrane perforation, calcium increase, and synaptotoxicity; and Abeta(17-42) induced mitochondrial toxicity similar to the full length Abeta(1-42), but was unable to induce membrane perforation and calcium increase, supporting the idea that it is less toxic in the non-amyloidogenic pathway. PMID- 26890762 TI - Japanese Care Location and Medical Procedures for People with Dementia in the Last Month of Life. AB - BACKGROUND: Dementia-related societies worldwide have called for palliative end of-life care for those suffering dementia; meanwhile, the Japanese dementia plan was revised on January 2015 to introduce into its objectives the support for end of-life care via increased social and health care collaboration. OBJECTIVE: The study focus was the use of medical procedures in the last month of life among dementia patients in different care locations in Japan. METHODS: This study was conducted using a retrospective study design. Data from the Survey of Institutions and Establishments for Long-Term Care, which is a nationally representative cross-sectional survey of the public long-term care insurance services, were used. The 6,148 patients who received end-of-life care in their own home, nursing homes, or hospitals in September 2007, 2010, and 2013 were included for analysis. The primary disease of each patient was based on the ICD 10 code; a diagnosis of dementia included F00 (Alzheimer's), F01 (vascular), F02 (other), and F03 (unspecified). RESULTS: Of 6,148 patients, 886 (14.4%) had dementia as a primary disease; most received care in the last month of life in nursing homes (48.0%) or hospitals (44.8%) rather than in their own home (7.2%). Patients were less likely to undergo pain management when their primary disease was dementia (adjusted odds ratio, 0.44; 95% confidence interval, 0.21-0.91). CONCLUSION: Education and policy efforts are required to provide palliative end of-life care to people with dementia at home. The national dementia plan should also explore possible approaches regarding pain management for dying people who have dementia. PMID- 26890760 TI - Self-Reported Traumatic Brain Injury and Mild Cognitive Impairment: Increased Risk and Earlier Age of Diagnosis. AB - This study examined whether history of traumatic brain injury (TBI) is associated with increased risk and earlier onset of mild cognitive impairment (MCI). Subjects with MCI (n = 3,187) and normal cognition (n = 3,244) were obtained from the National Alzheimer's Coordinating Center database. TBI was categorized based on lifetime reported TBI with loss of consciousness (LOC) without chronic deficit. Logistic regression was used to examine TBI history as a predictor of MCI, adjusted for demographics, apolipoprotein E-E4 (ApoE4), a composite vascular risk score, and history of psychiatric factors. ANCOVA was used to examine whether age at MCI diagnosis and estimated age of onset differed between those with (TBI+) and without (TBI-) a history of TBI. TBI history was a significant predictor (p < 0.01) and associated with increased odds of MCI diagnosis in unadjusted (OR = 1.25; 95% CI = 1.05-1.49) and adjusted models, accounting for age, education, ApoE4, and a composite vascular score (OR = 1.32; 95% CI = 1.10 1.58). This association, however, was largely attenuated (OR = 1.14; 95% CI = 0.94-1.37; p = 0.18) after adjustment for reported history of depression. MCI was diagnosed a mean of 2.3 years earlier (p < 0.001) in the TBI+ group, and although TBI+ subjects had an estimated mean of decline 1.7 years earlier, clinician-estimated age of onset failed to differ (p = 0.13) when gender and psychiatric factors were controlled. This is the first report of a possible role for TBI as a risk factor in MCI, but its association may be related to other factors such as gender and depression and requires further investigation. PMID- 26890764 TI - Cannabinoid Receptor 2 Participates in Amyloid-beta Processing in a Mouse Model of Alzheimer's Disease but Plays a Minor Role in the Therapeutic Properties of a Cannabis-Based Medicine. AB - The endogenous cannabinoid system represents a promising therapeutic target to modify neurodegenerative pathways linked to Alzheimer's disease (AD). The aim of the present study was to evaluate the specific contribution of CB2 receptor to the progression of AD-like pathology and its role in the positive effect of a cannabis-based medicine (1:1 combination of Delta9-tetrahidrocannabinol and cannabidiol) previously demonstrated to be beneficial in the AbetaPP/PS1 transgenic model of the disease. A new mouse strain was generated by crossing AbetaPP/PS1 transgenic mice with CB2 knockout mice. Results show that lack of CB2 exacerbates cortical Abeta deposition and increases the levels of soluble Abeta40. However, CB2 receptor deficiency does not affect the viability of AbetaPP/PS1 mice, does not accelerate their memory impairment, does not modify tau hyperphosphorylation in dystrophic neurites associated to Abeta plaques, and does not attenuate the positive cognitive effect induced by the cannabis-based medicine in these animals. These findings suggest a minor role for the CB2 receptor in the therapeutic effect of the cannabis-based medicine in AbetaPP/PS1 mice, but also constitute evidence of a link between CB2 receptor and Abeta processing. PMID- 26890763 TI - Associations between Serum Omega-3 Fatty Acid Levels and Cognitive Functions among Community-Dwelling Octogenarians in Okinawa, Japan: The KOCOA Study. AB - BACKGROUND: Epidemiological studies have found frequent consumption of fatty fish is protective against cognitive decline. However, the association between circulating omega-3 polyunsaturated fatty acid (PUFA) levels and cognitive functions among the oldest old is not well known. OBJECTIVE: To examine the association between serum PUFA levels and cognitive function among community dwelling, non-demented elderly aged over 80 years old. METHODS: The data came from the Keys to Optimal Cognitive Aging (KOCOA) study; an ongoing cohort of relatively healthy volunteers aged over 80 years old, living in Okinawa, Japan. One hundred eighty five participants (mean age 84.1+/-3.4 years) assessed in 2011 who were free from frank dementia (defined as Clinical Dementia Rating <1.0) were used for the current cross-sectional study. We examined whether serum omega-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), arachidonic acid (AA), EPA/AA ratio, DHA/AA ratio, and DHA+EPA are associated with (1) age and (2) global cognitive function (Japanese MMSE) and executive function (Verbal Fluency Letter). Data was analyzed univariately by t-test and multivariately by cumulative logistic regression models controlling for age, gender, years of education, obesity, hypertension, diabetes, and dyslipidemia. RESULTS: Serum DHA levels decreased with increasing age (p = 0.04). Higher global cognitive function was associated with higher levels of serum EPA (p = 0.03) and DHA + EPA (p = 0.03) after controlling for confounders. CONCLUSIONS: Higher serum EPA and DHA + EPA levels were independently associated with better scores on global cognitive function among the oldest old, free from dementia. Longitudinal follow-up studies are warranted. PMID- 26890766 TI - The Societal Cost of Dementia in Singapore: Results from the WiSE Study. AB - BACKGROUND: There is currently limited evidence on the economic burden that dementia exerts on multi-ethnic Asian populations. OBJECTIVE: The present study aimed to estimate the economic cost of dementia in Singapore. METHODS: We used data from the Well-being of the Singapore Elderly study, a nationally representative survey of the older Singapore Resident population aged 60 years and above. Generalized linear modeling was used to estimate factors associated with costs. RESULTS: The total cost of dementia in 2013 was estimated at S$532 million (95% CI, S$361 million to S$701 million) while the annual cost per person was estimated at S$10,245 per year (95% CI, S$6,954 to S$12,495). Apart from dementia, higher total societal cost were also significantly associated with older age, Indian ethnicity, and those who were diagnosed with heart problems, stroke, diabetes or depression, whereas being divorced/separated, lower education, and those who were diagnosed with hypertension were significantly associated with lower total societal cost. CONCLUSION: The study provides a rich body of information on healthcare utilization and cost of dementia, which is essential for future planning of services for the elderly population. PMID- 26890767 TI - Unmet Needs of Community-Dwelling Primary Care Patients with Dementia in Germany: Prevalence and Correlates. AB - BACKGROUND: To provide an optimal care for persons with dementia (PWD), their individual unmet needs have to be identified and comprehensively addressed. OBJECTIVES: Present analyses aim to describe the number and types of unmet needs of German primary care patients screened positive for dementia and factors associated with the number of unmet needs. METHODS: DelpHi-MV (Dementia: life- and person-centered help in Mecklenburg-Western Pomerania) is a general practitioner-based, cluster-randomized controlled intervention trial. Analyses are based on the baseline data of 227 PWD (>=70 years, living at home) of the intervention group who had screened positive for dementia (DemTect<9) and received a standardized computer-assisted needs assessment. RESULTS: PWD had on average 8.77+/-5.04 unmet needs (Range = 0-31). More than 90% of the PWD had three or more unmet needs. Unmet needs were identified across all predefined 26 subcategories. The majority of unmet needs occurred in the domains "nursing treatment and care" (38%), "social counseling and legal support" (20%), and "pharmacological treatment and care" (15%). More impairment in the activities of daily living was the only factor that was significantly associated with a higher number of unmet needs, independent of age, gender, living situation, presence of an informal caregiver, cognitive impairment, and depression. CONCLUSIONS: Present results demonstrate that community-dwelling PWD had a broad range of varying unmet needs. These findings emphasize the importance of a comprehensive needs assessment that allows the identification of individual needs as the basis for a tailored intervention- such as Dementia Care Management- that can address these needs. PMID- 26890765 TI - Increased Electron Paramagnetic Resonance Signal Correlates with Mitochondrial Dysfunction and Oxidative Stress in an Alzheimer's disease Mouse Brain. AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized clinically by cognitive decline and memory loss. The pathological features are amyloid-beta peptide (Abeta) plaques and intracellular neurofibrillary tangles. Many studies have suggested that oxidative damage induced by reactive oxygen species (ROS) is an important mechanism for AD progression. Our recent study demonstrated that oxidative stress could further impair mitochondrial function. In the present study, we adopted a transgenic mouse model of AD (mAPP, overexpressing AbetaPP/Abeta in neurons) and performed redox measurements using in vivo electron paramagnetic resonance (EPR) imaging with methoxycarbamyl-proxyl (MCP) as a redox-sensitive probe for studying oxidative stress in an early stage of pathology in a transgenic AD mouse model. Through assessing oxidative stress, mitochondrial function and cognitive behaviors of mAPP mice at the age of 8-9 months, we found that oxidative stress and mitochondrial dysfunction appeared in the early onset of AD. Increased ROS levels were associated with defects of mitochondrial and cognitive dysfunction. Notably, the in vivo EPR method offers a unique way of assessing tissue oxidative stress in living animals under noninvasive conditions, and thus holds a potential for early diagnosis and monitoring the progression of AD. PMID- 26890768 TI - Delusions in Patients with Alzheimer's Disease: A Multidimensional Approach. AB - In Alzheimer's disease (AD) patients with delusions, clinical outcomes and mortality result from a combination of psychological, biological, functional, and environmental factors. We determined the effect of delusions on mortality risk, clinical outcomes linked to comprehensive geriatric assessment (CGA), cognitive, depressive, and neuropsychiatric symptoms (NPS) in 380 consecutive AD patients with Mini-Mental State Examination, Clinical Dementia Rating scale, 15-item Geriatric Depression Scale, and Neuropsychiatric Inventory (NPI), assessing one year mortality risk using the Multidimensional Prognostic Index (MPI). We included 121 AD patients with delusions (AD-D) and 259 AD patients without delusions (AD-noD). AD-D patients were significantly older, with higher age at onset and cognitive impairment, a more severe stage of dementia, and more depressive symptoms than AD-noD patients. Disease duration was slightly higher in AD-D patients than in those without delusions, although this difference was not statistically significant. At CGA, AD-D patients showed a higher grade of disability in basic and instrumental activities of daily living, and an increased risk of malnutrition and bedsores. The two groups of patients significantly differed in MPI score (AD-D: 0.65 versus AD-noD: 0.51, p < 0.0001) and MPI grade. AD-D patients showed also a significant higher score in NPI of the following NPS than AD-noD patients: hallucinations, agitation/aggression, depression mood, apathy, irritability/lability, aberrant motor activity, sleep disturbances, and eating disorders. Therefore, AD-D patients showed higher dementia severity, and higher impairment in cognitive and depressive symptoms, and several neuropsychiatric domains than AD-noD patients, and this appeared to be associated with higher multidimensional impairment and increased risk of mortality. PMID- 26890769 TI - Longitudinal Changes in Functional Brain Connectivity Predicts Conversion to Alzheimer's Disease. AB - This longitudinal study investigates the modifications in structure and function occurring to typical Alzheimer's disease (AD) brains over a 2-year follow-up, from pre-dementia stages of disease, with the aim of identifying biomarkers of prognostic value. Thirty-one patients with amnestic mild cognitive impairment were recruited and followed-up with clinical, neuropsychological, and MRI assessments. Patients were retrospectively classified as AD Converters or Non Converters, and the data compared between groups. Cross-sectional MRI data at baseline, assessing volume and functional connectivity abnormalities, confirmed previous findings, showing a more severe pattern of regional grey matter atrophy and default-mode network disconnection in Converters than in Non-Converters. Longitudinally, Converters showed more grey matter atrophy in the frontotemporal areas, accompanied by increased connectivity in the precuneus. Discriminant analysis revealed that functional connectivity of the precuneus within the default mode network at baseline is the parameter able to correctly classify patients in Converters and Non-Converters with high sensitivity, specificity, and accuracy. PMID- 26890771 TI - Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study. AB - BACKGROUND: Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. OBJECTIVE: We aimed to examine the association of serum vitamin D levels with incident all cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function. METHODS: Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). RESULTS: In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (beta= -0.03 to -0.05+/-0.02) and the Hooper Visual Organization Test (beta= -0.09 to -0.12+/-0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (beta= -0.01+/-0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. CONCLUSIONS: In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function. PMID- 26890770 TI - Characteristics of Alzheimer's Disease Patients with Severe Executive Disorders. AB - BACKGROUND: Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations. OBJECTIVE: The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction. METHODS: The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery. RESULTS: 381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as >=2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months. CONCLUSIONS: Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes. PMID- 26890774 TI - Apathy and Attentional Biases in Alzheimer's Disease. AB - BACKGROUND: Apathy, one of the most prevalent neuropsychiatric symptoms in Alzheimer's disease (AD), can be difficult to assess as cognition deteriorates. There is a need for more objective assessments that do not rely on patient insight, communicative capacities, or caregiver observation. OBJECTIVE: We measured visual scanning behavior, using an eye-tracker, to explore attentional bias in the presence of competing stimuli to assess apathy in AD patients. METHODS: Mild-to-moderate AD patients (Standardized Mini-Mental Status Examination, sMMSE >10) were assessed for apathy (Neuropsychiatric Inventory [NPI] apathy, Apathy Evaluation Scale [AES]). Participants were presented with 16 slides, each containing 4 images of different emotional themes (2 neutral, 1 social, 1 dysphoric). The duration of time spent, and fixation frequency on images were measured. RESULTS: Of the 36 AD patients (14 females, age = 78.2+/ 7.8, sMMSE = 22.4+/-3.5) included, 17 had significant apathy (based on NPI apathy >=4) and 19 did not. These groups had comparable age and sMMSE. Repeated-measures analysis of covariance models, controlling for total NPI, showed group (apathetic versus non-apathetic) by image (social versus dysphoric) interactions for duration (F(1,32) = 4.31, p = 0.046) and fixation frequency (F(1,32) = 11.34, p = 0.002). Apathetic patients demonstrated reduced duration and fixation frequency on social images compared with non-apathetic patients. Additionally, linear regression models suggest that more severe apathy predicted decreasing fixation frequency on social images (R2 = 0.26, Adjusted R2 = 0.19, F(3,32) = 3.65, p = 0.023). CONCLUSION: These results suggest that diminished attentional bias toward social-themed stimuli is a marker of apathy in AD. Measurements of visual scanning behavior may have the potential to predict and monitor treatment response in apathy. PMID- 26890773 TI - Clearing Amyloid-beta through PPARgamma/ApoE Activation by Genistein is a Treatment of Experimental Alzheimer's Disease. AB - Amyloid-beta (Abeta) clearance from brain, which is decreased in Alzheimer's disease, is facilitated by apolipoprotein E (ApoE). ApoE is upregulated by activation of the retinoid X receptor moiety of the RXR/PPARgamma dimeric receptor. Genistein, a non-toxic, well-tested, and inexpensive drug activates the other moiety of the receptor PPARgamma. Treatment of an Alzheimer's disease mouse model with genistein results in a remarkable and rapid improvement in various parameters of cognition, such as hippocampal learning, recognition memory, implicit memory, and odor discrimination. This is associated with a lowering of Abeta levels in brain, in the number and the area of amyloid plaques (confirmed in vivo by positron emission tomography) as well as in microglial reactivity. Finally, incubation of primary astrocytes with genistein results in a PPARgamma mediated increased release of ApoE. Our results strongly suggest that controlled clinical trials should be performed to test the effect of genistein as treatment of human Alzheimer's disease. PMID- 26890772 TI - Characterization of Amyloid-beta Deposits in Bovine Brains. AB - Amyloid-beta (Abeta) deposits are seen in aged individuals of many mammalian species that possess the same aminoacid sequence as humans. This study describes Abeta deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years. Extracellular and intracellular Abeta deposition was detected with 4G8 antibody in the cortex, hippocampus, and cerebellum. X-34 staining failed to stain Abeta deposits, indicating the non beta-pleated nature of these deposits. Western blot analysis and surface-enhanced laser desorption/ionization time-of flight (SELDI-TOF) mass spectrometry revealed in Tris, Triton, and formic acid fractions the presence of different Abeta peptides, characterized mainly by C terminally truncated forms. Exploration of the genetic variability of APOE, PSEN1, and PSEN2 genes involved in Alzheimer's disease pathogenesis revealed several previously unreported polymorphisms. This study demonstrates certain similarities between Abeta deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging. Furthermore, the identification of the same Abeta peptides reported in humans, but unable to form aggregates, supports the hypothesis that cattle may be protected against amyloid plaque formation. PMID- 26890776 TI - Cerebral Amyloid Angiopathy (CAA)-Related Inflammation: Comparison of Inflammatory CAA and Amyloid-beta-Related Angiitis. AB - Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a relatively rare syndrome of reversible encephalopathy and could be divided into two subtypes of inflammatory CAA (ICAA) and amyloid-beta-related angiitis (ABRA) according to histopathology. We present a case of pathologically proved ABRA with partial seizures and headache, and a focal lesion in the right temporal lobes on magnetic resonance imaging. Summarized from previous 139 ABRA and ICAA cases, ABRA is preferred when the lesion is enhanced on MRI and requires combination drug therapy, while ICAA is highly suspected with ApoE genotype of E4/E4. More clinical markers for diagnosis of CAA-ri warrant further researches. PMID- 26890775 TI - Preliminary Study of Plasma Exosomal Tau as a Potential Biomarker for Chronic Traumatic Encephalopathy. AB - BACKGROUND: Chronic traumatic encephalopathy (CTE) is a tauopathy associated with prior exposure to repetitive head impacts, such as those incurred through American football and other collision sports. Diagnosis is made through neuropathological examination. Many of the clinical features of CTE are common in the general population, with and without a history of head impact exposure, making clinical diagnosis difficult. As is now common in the diagnosis of other neurodegenerative disorders, such as Alzheimer's disease, there is a need for methods to diagnose CTE during life through objective biomarkers. OBJECTIVE: The aim of this study was to examine tau-positive exosomes in plasma as a potential CTE biomarker. METHODS: Subjects were 78 former National Football League (NFL) players and 16 controls. Extracellular vesicles were isolated from plasma. Fluorescent nanoparticle tracking analysis was used to determine the number of vesicles staining positive for tau. RESULTS: The NFL group had higher exosomal tau than the control group (p < 0.0001). Exosomal tau discriminated between the groups, with 82% sensitivity, 100% specificity, 100% positive predictive value, and 53% negative predictive value. Within the NFL group, higher exosomal tau was associated with worse performance on tests of memory (p = 0.0126) and psychomotor speed (p = 0.0093). CONCLUSION: These preliminary findings suggest that exosomal tau in plasma may be an accurate, noninvasive CTE biomarker. PMID- 26890777 TI - Patterns of Brain Iron Accumulation in Vascular Dementia and Alzheimer's Dementia Using Quantitative Susceptibility Mapping Imaging. AB - BACKGROUND: Emerging evidence suggests that the excessive accumulation of iron in subcortical and deep gray matter has been related to dementia. However, the presence and pattern of iron accumulation in vascular dementia (VaD) and Alzheimer's disease (AD) are rarely investigated. OBJECTIVE: To examine and compare the pattern and presence of brain iron accumulation of VaD and AD using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Twelve patients with VaD, 27 patients with AD, and 18 control subjects were recruited in this institutional review-board approved study. Susceptibility maps were reconstructed from a three-dimensional multiecho spoiled gradient-echo sequence. Four regions of interest were drawn manually on QSM images, namely the globus pallidus, putamen, caudate nucleus, and pulvinar nucleus of the thalamus. Comparisons of patient demographics, and iron concentrations among the VaD, AD, and control subjects were assessed using analysis of variance and post-hoc analyses. The relationships of age and cognitive state with susceptibility values were assessed using partial correlation analysis. RESULTS: In VaD and AD, overall susceptibility values were higher than those of control subjects. A significant difference in susceptibility values was found in the putamen and caudate nucleus (p < 0.001 and p = 0.002, respectively). However, susceptibility values did not differ between VaD and AD. Age and cognitive deficit severity were not related to susceptibility values in the VaD and AD groups. CONCLUSION: Increased iron deposition in the putamen and caudate nucleus in VaD and AD patients was not associated with age or the severity of cognitive deficits. Further evaluations are needed to determine the temporal changes in iron load and their diagnostic role in dementia pathology. PMID- 26890779 TI - Tau Accumulation in Primary Motor Cortex of Variant Alzheimer's Disease with Spastic Paraparesis. AB - We studied topographic distribution of tau and amyloid-beta in a patient with variant Alzheimer's disease with spastic paraparesis (VarAD) by comparing AD patients. The proband developed progressive memory impairment, dysarthria, and spastic paraparesis at age 23. Heterozygous missense mutation (L166P) was found in exon 6 of presenilin-1 gene. The proband showed prominently increased amyloid binding in striatum and cerebellum and asymmetrical tau binding in the primary sensorimotor cortex contralateral to the side more affected by spasticity. We suspect that upper motor neuron dysfunctions may be attributed to excessive abnormal tau accumulation rather than amyloid-beta in the primary motor cortex. PMID- 26890778 TI - Evaluation of Cerebrospinal Fluid Assay Variability in Alzheimer's Disease. AB - Studies of cerebrospinal fluid (CSF) biomarkers in Alzheimer's disease (AD) have indicated that much of the variability observed in the biomarkers may be due to measurement error. Biomarkers are often obtained with measurement error, which may make the diagnostic biomarker appear less effective than it truly is. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, technical replicates of CSF biomarkers are available; the National Alzheimer's Coordinating Center database contains longitudinal replicates of CSF biomarkers. We focus on the area under the receiver operating characteristic curve (AUC) as the measure of diagnostic effectiveness for differentiating AD from normal cognition using CSF biomarkers and compare AUC estimates obtained by a more standard, naive method (which uses a single observation per subject and ignores measurement error) to a maximum likelihood (ML) based method (which uses all replicates per subject and adjusts for measurement error). The choice of analysis method depends upon the noise to signal ratio (i.e., the magnitude of the measurement error variability relative to the true biomarker variability); moderate to high ratios may significantly bias the naive AUC estimate, and the ML-based method would be preferred. The noise to signal ratios were low for the ADNI biomarkers but high for the tTau and pTau biomarkers in NACC. Correspondingly, the naive and ML-based AUC estimates were nearly identical in the ADNI data but dissimilar for the tTau and pTau biomarkers in the NACC data. Therefore, using the naive method is adequate for analysis of CSF biomarkers in the ADNI study, but the ML method is recommended for the NACC data. PMID- 26890780 TI - Low Plasma Cholinesterase Activities are Associated with Deficits in Spatial Orientation, Reduced Ability to Perform Basic Activities of Daily Living, and Low Body Mass Index in Patients with Progressed Alzheimer's Disease. AB - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by a central cholinergic deficit. Non-neuronal cholinergic changes are, however, described as well. Here we focused on possible changes in the activity of the plasma cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), in hospitalized AD patients. We analyzed plasma AChE and BChE activities with regards to age, gender, body mass index (BMI), cognitive functions, and ability to perform activities of daily living in AD patients in comparison to healthy subjects. We observed lower AChE activity and trend toward lower BChE activity in AD patients, which both correlated with low BMI. AD patients unable to perform basic activities of daily living (feeding, bathing, dressing, and grooming) showed reduced plasma AChE activities, while worse spatial orientation was linked to lower BChE activities. Three out of four AD patients with the lowest BChE activities died within one year. In conclusion, progressed AD was accompanied by lower plasma AChE activity and trend toward lower BChE activity, which correlated with BMI and deficits in different components of the AD. PMID- 26890781 TI - Fluoxetine Treatment Induces Seizure Behavior and Premature Death in APPswe/PS1dE9 Mice. AB - Treatment of Alzheimer's disease (AD) patients with the antidepressant fluoxetine is known to improve memory and cognitive function. However, the mechanisms underlying these effects are largely unknown. To unravel these mechanisms, we aimed to treat APPswe/PS1dE9 mice with fluoxetine. Unexpectedly, with time, an increased number of animals displayed seizure behavior and died. Although spontaneous behavioral seizures have been reported previously in this mouse model, the observation of seizures and death consequential to fluoxetine treatment is new. Our results warrant further research on the underlying mechanisms as this may refine the treatment of AD patients. PMID- 26890783 TI - The Role of Ethnicity in Alzheimer's Disease: Findings From The C-PATH Online Data Repository. AB - BACKGROUND: Ethnic minorities seem to be at an increased risk of Alzheimer's disease (AD). However, little is known about ethnic differences and the risks of early onset AD (EOAD). OBJECTIVE: Cognitive function changes over time and odds of EOAD by ethnicity were analyzed by the mixed model and the logistic regression. METHODS: Information on demographics, self-reported co-morbidities, cognitive functions (MMSE and ADAS-COG), and ApoE genotypes were collected for 6,500 subjects with AD obtained from the placebo arm of clinical trials; this data was examined by ethnicities: Caucasian, Asian, African American, Hispanic, and other minorities--including Native Alaskans, Americans, and Hawaiians. RESULTS: Of the total subjects, Caucasians accounted for 89.0% , followed by 4.7% Asians, 2.7% African Americans, 2.4% Hispanics, and 1.2% Native Americans, Alaskans, and Hawaiians. Age, gender, EOAD status, co-morbidities, family history of AD, and ApoE genotypes were significantly different by ethnicity. ApoE E2 allele is possibly overrepresented in the Native Americans, Africans, Hawaiians, and African Americans. A significant interaction with time, ethnicity, and cognitive performance was found, indicating more cognitive deterioration in other minorities than Caucasians for mini-mental state (p < 0.01). After adjusting for co-morbidities and gender, the odds of EOAD among African Americans (OR: 1.6, 95% CI: 1.1-2.4) and Native Alaskans, Americans, and Hispanics (OR: 2.1, 95% CI: 1.2 3.5) were significantly higher, compared with Caucasians. CONCLUSIONS: Ethnicity may impact AD through age of onset, co-morbidities, family history, ApoE gene status, and cognitive change over time. The greater odds of EOAD among African Americans, Alaskans, and Hawaiians suggest that some ethnicities may be at risk of AD at a younger age. PMID- 26890785 TI - Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein. AB - BACKGROUND: Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. OBJECTIVE: Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p Tau/Tau ratio to specify its ability to distinguish AD from CJD. METHODS: Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. RESULTS: Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001). CONCLUSION: Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD. PMID- 26890782 TI - Do Microglia Default on Network Maintenance in Alzheimer's Disease? AB - Although the cause of Alzheimer's disease (AD) remains unknown, a number of new findings suggest that the immune system may play a critical role in the early stages of the disease. Genome-wide association studies have identified a wide array of risk-associated genes for AD, many of which are associated with abnormal functioning of immune cells. Microglia are the brain's immune cells. They play an important role in maintaining the brain's extracellular environment, including clearance of aggregated proteins such as amyloid-beta (Abeta). Recent studies suggest that microglia play a more active role in the brain than initially considered. Specifically, microglia provide trophic support to neurons and also regulate synapses. Microglial regulation of neuronal activity may have important consequences for AD. In this article we review the function of microglia in AD and examine the possible relationship between microglial dysfunction and network abnormalities, which occur very early in disease pathogenesis. PMID- 26890784 TI - Discrepancy in Expression of beta-Secretase and Amyloid-beta Protein Precursor in Alzheimer-Related Genes in the Rat Medial Temporal Lobe Cortex Following Transient Global Brain Ischemia. AB - Brain ischemia may be causally related with Alzheimer's disease. Presumably, beta secretase and amyloid-beta protein precursor gene expression changes may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both beta-secretase and amyloid-beta protein precursor genes in the medial temporal lobe cortex with the use of quantitative rtPCR analysis following 10-min global brain ischemia in rats with survival of 2, 7, and 30 days. The greatest significant overexpression of beta-secretase gene was noted on the 2nd day, while on days 7-30 the expression of this gene was only modestly downregulated. Amyloid-beta protein precursor gene was downregulated on the 2nd day, but on days 7-30 postischemia, there was a significant reverse tendency. Thus, the demonstrated alterations indicate that the considerable changes of expression of beta-secretase and amyloid-beta protein precursor genes may be connected with a response of neurons in medial temporal lobe cortex to transient global brain ischemia. Finally, the ischemia-induced gene changes may play a key role in a late and slow onset of Alzheimer-type pathology. PMID- 26890786 TI - Intranasal TAT-haFGF Improves Cognition and Amyloid-beta Pathology in an AbetaPP/PS1 Mouse Model of Alzheimer's Disease. AB - Neurotoxic amyloid-beta (Abeta) peptide causing cognitive function disabilities is one of the most characteristic pathological features in Alzheimer's disease (AD). A novel fusion protein, TAT-haFGF, was administrated to AbetaPP/PS1 transgenic mice by intravenous (IV) injection and intranasal (IN) delivery, respectively, for 5 weeks to compare the pharmacodynamics between the two routes of administration. Our results showed that IN administration of TAT-haFGF improved cognition and reduced Abeta plaques more significantly in AbetaPP/PS1 mice, when compared with IV injection. Our new findings suggest that TAT-haFGF might be a promising new therapy to attenuate AD pathological process. PMID- 26890789 TI - Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort. AB - BACKGROUND AND AIMS: Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice. MATERIALS AND METHODS: We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea. RESULTS: During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7+/-10.7 vs. 53.3+/ 10.4 years, p < 0.001), had more hospital visits (121.94+/-126.88 days/PY, p < 0.001), had a longer hospital stays (16.13+/-29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56+/-4,056.38 vs. $1,336.37+/-3,403.39 /PY, p < 0.001) than subjects without hypoglycemia. CONCLUSION: Hypoglycemia related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system. PMID- 26890791 TI - Selective focusing through target identification and experimental acoustic signature extraction: Numerical experiments. AB - Using transducer arrays and appropriate emission delays allow to focus acoustic waves at a chosen location in a medium. The focusing spatial accuracy depends on the accurate knowledge of its acoustic properties. When those properties are unknown, methods based on the Time-Reversal principle allow accurate focusing. Still, these methods are either intrusive (an active source has to be introduced at the target location first), either blind (the target cannot be selected in the presence of several objects.) The purpose of the present work is to achieve non invasive accurate focusing on a selected target using inaccurate acoustic properties for the investigated medium. Potential applications are for instance noninvasive surgery based on High Intensity Focused Ultrasound (HIFU). Numerical experiments are presented and demonstrate accurate focusing on a previously designated target located in an unknown heterogeneous medium. PMID- 26890790 TI - Local Drug Infiltration Analgesia During Knee Surgery to Reduce Postoperative Pain in Rats. AB - BACKGROUND AND OBJECTIVES: There is increasing interest in local infiltration analgesia (LIA) to reduce postoperative pain with knee surgery. Despite widespread use of LIA, wide variations in drug combinations, infiltration techniques, and the concomitant use of systemic analgesics have made it difficult to determine the optimal drug combination for LIA.Using a previously validated animal knee surgery model, we aimed to determine the optimal combination of medications to reduce postoperative pain, and the best anatomical location and timing for local drug injection during surgery. METHODS: Knee surgery was performed in an adult rat model under isoflurane anesthesia. During surgery, combinations of bupivacaine, ketorolac, dexamethasone, and morphine were injected around the knee and compared to saline placebo. Similar medications were injected systemically as a comparator group. Postoperative pain was assessed by measuring spontaneous rearing activity. Injections were given after bone drilling and/or just before wound closure. RESULTS: The 3-drug LIA combination of bupivacaine, ketorolac, and dexamethasone increased rearing (decreased pain) at 2 hours (P = 0.0198) and 24 hours (P = 0.0384) postsurgery compared to saline. The same drugs injected systemically had no effect. The ketorolac/dexamethasone combination for LIA was also effective at 2 hours (P = 0.0006) and 24 hours (P = 0.0279), and ketorolac alone reduced pain at 2 hours (P = 0.0045). Bupivacaine alone was less effective, and the addition of morphine had no effect. The 3-drug combination infiltrated just after creating holes in bone was more effective than when given into the wound just before wound closure. CONCLUSIONS: Our animal study suggests that clinical trials with LIA combinations of local anesthetic, nonsteroidal anti inflammatory drug, and corticosteroid might be useful for reducing postoperative pain after knee surgery, with the nonsteroidal anti-inflammatory drug having the greatest effect.Perioperative physicians should consider delivering LIA earlier during the procedure as opposed to solely at the time of wound closure. PMID- 26890788 TI - Time-Course Transcriptome Analysis Reveals Resistance Genes of Panax ginseng Induced by Cylindrocarpon destructans Infection Using RNA-Seq. AB - Panax ginseng C. A. Meyer is a highly valued medicinal plant. Cylindrocarpon destructans is a destructive pathogen that causes root rot and significantly reduces the quality and yield of P. ginseng. However, an efficient method to control root rot remains unavailable because of insufficient understanding of the molecular mechanism underlying C. destructans-P. ginseng interaction. In this study, C. destructans-induced transcriptomes at different time points were investigated using RNA sequencing (RNA-Seq). De novo assembly produced 73,335 unigenes for the P. ginseng transcriptome after C. destructans infection, in which 3,839 unigenes were up-regulated. Notably, the abundance of the up regulated unigenes sharply increased at 0.5 d postinoculation to provide effector triggered immunity. In total, 24 of 26 randomly selected unigenes can be validated using quantitative reverse transcription (qRT)-PCR. Gene ontology enrichment analysis of these unigenes showed that "defense response to fungus", "defense response" and "response to stress" were enriched. In addition, differentially expressed transcription factors involved in the hormone signaling pathways after C. destructans infection were identified. Finally, differentially expressed unigenes involved in reactive oxygen species and ginsenoside biosynthetic pathway during C. destructans infection were indentified. To our knowledge, this study is the first to report on the dynamic transcriptome triggered by C. destructans. These results improve our understanding of disease resistance in P. ginseng and provide a useful resource for quick detection of induced markers in P. ginseng before the comprehensive outbreak of this disease caused by C. destructans. PMID- 26890793 TI - Production of phenol-rich bio-oil during catalytic fixed-bed and microwave pyrolysis of palm kernel shell. AB - Catalytic fixed-bed and microwave pyrolysis of palm kernel shell using activated carbon (AC) and lignite char (LC) as catalysts and microwave receptors are investigated. The effects of process parameters including temperature and biomass:catalyst ratio on the yield and composition of pyrolysis products were studied. The addition of catalyst increased the bio-oil yield, but decreased the selectivity of phenol in fixed-bed. Catalytic microwave pyrolysis of PKS significantly enhanced the selectivity of phenol production. The highest concentration of phenol in bio-oil of 64.58 %(area) and total phenolics concentration of 71.24 %(area) were obtained at 500 degrees C using AC. Fourier transform infrared spectroscopy (FTIR) results indicated that concentration of OH, CH, CO and CO functional groups in char samples decreased after pyrolysis. Scanning electron microscopy (SEM) analysis clearly indicated the development of liquid phase in biomass particles during microwave pyrolysis, and the mechanism is also discussed. PMID- 26890792 TI - Kinetics characteristics of straw semi-char gasification with carbon dioxide. AB - The gasification process has promising potential as a solution for the current global energy problem. Kinetics characteristics of straw semi-char gasification were investigated. The main influence factors of gasification, which include bio char particle size, pyrolysis temperature and pyrolysis atmosphere, were studied. The smaller the particle size is, the higher is the conversion rate. The gasification reactivity of semi-chars increases with pyrolysis temperature and reaches its maximum at approximately 400 degrees C. The straw semi-char obtained in an H2 pyrolysis atmosphere has the best gasification reactivity, while the semi-char obtained in a CO2 atmosphere has the worst reactivity. In addition, characteristics of semi-char were systematically tested. A random pore model, unreacted core shrinking model and integrated model were employed to describe the reactive behavior of semi-chars. Gasification kinetics parameters were calculated. The random pore model fitting result is in better agreement with the experiments than that of the other two models. PMID- 26890794 TI - Hydrolysate of lipid extracted microalgal biomass residue: An algal growth promoter and enhancer. AB - The present study demonstrates the utilization of the algal hydrolysate (AH) prepared from lipid extracted residual harmful bloom-forming cyanobacteria Lyngbya majuscula biomass, as a growth supplement for the cultivation of green microalgae Chlorella vulgaris. BG-11 replacements with AH in different proportions significantly affects the cell count, dry cell weight (DCW), biomass productivity (BP) and pigments concentration. Among all, 25% AH substitution in BG11 media was found to be optimum which enhanced DCW, BP and pigments content by 39.13%, 40.81% and 129.47%, respectively, compared to control. The lipid content (31.95%) was also significantly higher in the 25% AH replacement. The volumetric productivity of neutral lipids (ideal for biodiesel) and total protein content of the cells significantly increased in all AH substitutions. Thus, lipid extracted microalgal biomass residue (LMBR) hydrolysate can be a potential growth stimulating supplement for oleaginous microalgae C. vulgaris. PMID- 26890795 TI - Chemical composition, pretreatments and saccharification of Senna siamea (Lam.) H.S. Irwin & Barneby: An efficient biomass producing tree legume. AB - Protocols were developed for efficient release of glucose from the biomass of Senna siamea, one of the highly efficient biomass producing tree legumes. Composition of mature, 1year and 2years coppice biomass were analysed. For the hydrolysis of the glucan, two pretreatments, cellulose solvent- and organic solvent-based lignocellulose fractionation (COSLIF) and alkali (sodium hydroxide) were used; COSLIF (85% phosphoric acid, 45min incubation at 50 degrees C) pretreated mature biomass exhibited best result in which 88.90% glucose released after 72h of incubation with the use of 5 filter paper units (FPU) of cellulase and 10 international units (IU) of beta-glucosidase per gram of glucan. Of the biomass of different particle sizes (40-200mesh) used for saccharification, 40 60mesh shown the maximum glucose release. COSLIF pretreated mature, 1year and 2years coppice biomass showed equivalent glucose release profiles. PMID- 26890797 TI - A new bioenergetic and thermodynamic approach to batch photoautotrophic growth of Arthrospira (Spirulina) platensis in different photobioreactors and under different light conditions. AB - Photobioreactor configuration, mode of operation and light intensity are known to strongly impact on cyanobacteria growth. To shed light on these issues, kinetic, bioenergetic and thermodynamic parameters of batch Arthrospira platensis cultures were estimated along the time at photosynthetic photon flux density (PPFD) of 70MUmolm(-2)s(-1) in different photobioreactors with different surface/volume ratio (S/V), namely open pond (0.25cm(-1)), shaken flask (0.48cm(-1)), horizontal photobioreactor (HoP) (1.94cm(-1)) and helicoidal photobioreactor (HeP) (3.88cm( 1)). Maximum biomass concentration and productivity remarkably increased with S/V up to 1.94cm(-1). HoP was shown to be the best-performing system throughout the whole runs, while HeP behaved better only at the start. Runs carried out in HoP increasing PPFD from 40 to 100MUmolm(-2)s(-1) revealed a progressive enhancement of bioenergetics and thermodynamics likely because of favorable light distribution. HoP appeared to be a promising configuration to perform high-yield indoor cyanobacterial cultures. PMID- 26890796 TI - Enhanced dark hydrogen fermentation by addition of ferric oxide nanoparticles using Enterobacter aerogenes. AB - Ferric oxide nanoparticles (FONPs) were used to facilitate dark hydrogen fermentation using Enterobacter aerogenes. The hydrogen yield of glucose increased from 164.5+/-2.29 to 192.4+/-1.14mL/g when FONPs concentration increased from 0 to 200mg/L. SEM images of E. aerogenes demonstrated the existence of bacterial nanowire among cells, suggesting FONPs served as electron conduits to enhance electron transfer. TEM showed cellular internalization of FONPs, indicating hydrogenase synthesis and activity was potentially promoted due to the released iron element. When further increasing FONPs concentration to 400mg/L, the hydrogen yield of glucose decreased to 147.2+/-2.54mL/g. Soluble metabolic products revealed FONPs enhanced acetate pathway of hydrogen production, but weakened ethanol pathway. This shift of metabolic pathways allowed more nicotinamide adenine dinucleotide for reducing proton to hydrogen. PMID- 26890798 TI - Potential of genetically engineered hybrid poplar for pyrolytic production of bio based phenolic compounds. AB - Wild-type and two genetically engineered hybrid poplar lines were pyrolyzed in a micro-pyrolysis (Py-GC/MS) and a bench scale setup for fast and intermediate pyrolysis studies. Principal component analysis showed that the pyrolysis vapors obtained by micro-pyrolysis from wood of caffeic acid O-methyltransferase (COMT) and caffeoyl-CoA O-methyltransferase (CCoAOMT) down-regulated poplar trees differed significantly from the pyrolysis vapors obtained from non-transgenic control trees. Both fast micro-pyrolysis and intermediate pyrolysis of transgenic hybrid poplars showed that down-regulation of COMT can enhance the relative yield of guaiacyl lignin-derived products, while the relative yield of syringyl lignin derived products was up to a factor 3 lower. This study indicates that lignin engineering via genetic modifications of genes involved in the phenylpropanoid and monolignol biosynthetic pathways can help to steer the pyrolytic production of guaiacyl and syringyl lignin-derived phenolic compounds such as guaiacol, 4 methylguaiacol, 4-ethylguaiacol, 4-vinylguaiacol, syringol, 4-vinylsyringol, and syringaldehyde present in the bio-oil. PMID- 26890799 TI - Efficient conversion of crude glycerol from various industrial wastes into single cell oil by yeast Yarrowia lipolytica. AB - In this study, crude glycerol from various industries was used to produce lipids via wild type Yarrowia lipolytica A101. We tested samples without any prior purification from five different waste products; each contained various concentrations of glycerol (42-87%) as the sole carbon source. The best results for lipid production were obtained for medium containing glycerol from fat saponification. This reached 1.69gL(-1) (25% of total cell dry weight) with a biomass yield of 0.17gg(-1) in the flasks experiment. The batch cultivation in a bioreactor resulted in enhanced lipid production-it achieved 4.72gL(-1) with a biomass yield 0.21gg(-1). Moreover, the properly selected batch of crude glycerol provides a defined fatty acid composition. In summary, this paper shows that crude glycerol from soap production could be efficiently converted to single cell oil without any prior purification. PMID- 26890800 TI - Imputation of missing covariate values in epigenome-wide analysis of DNA methylation data. AB - DNA methylation is a widely studied epigenetic mechanism and alterations in methylation patterns may be involved in the development of common diseases. Unlike inherited changes in genetic sequence, variation in site-specific methylation varies by tissue, developmental stage, and disease status, and may be impacted by aging and exposure to environmental factors, such as diet or smoking. These non-genetic factors are typically included in epigenome-wide association studies (EWAS) because they may be confounding factors to the association between methylation and disease. However, missing values in these variables can lead to reduced sample size and decrease the statistical power of EWAS. We propose a site selection and multiple imputation (MI) method to impute missing covariate values and to perform association tests in EWAS. Then, we compare this method to an alternative projection-based method. Through simulations, we show that the MI based method is slightly conservative, but provides consistent estimates for effect size. We also illustrate these methods with data from the Atherosclerosis Risk in Communities (ARIC) study to carry out an EWAS between methylation levels and smoking status, in which missing cell type compositions and white blood cell counts are imputed. PMID- 26890801 TI - Treatment of Xanthelasma Palpebrarum With Intralesional Pingyangmycin. AB - BACKGROUND: Xanthelasma palpebrarum (xanthelasma) is the most common type of cutaneous xanthoma, and many patients tend to seek medical treatments for cosmetic reasons. Many methods treating xanthelasma have been proposed, but none of these options can be regarded as a perfect solution. OBJECTIVE: To study and evaluate the intralesional injection treatment of xanthelasma with pingyangmycin, which has been widely used as a broad-spectrum antitumor antibiotic. MATERIALS AND METHODS: 21 lesions in 12 patients were treated by intralesional pingyangmycin. Photographs were taken before and after each treatment session. Patients were followed up for 7 to 36 months. RESULTS: All patients except one received satisfactory results after up to 2 sessions. Only 1 patient had a local recurrence 1 year after the treatment. No severe complications such as infection, atrophy, ulceration, or scar were noticed. CONCLUSION: Intralesional pingyangmycin is a cheap, effective, and safe treatment for xanthelasma, which has been well accepted by patients. PMID- 26890802 TI - A Comparative Split-Face Study Using Different Mild Purpuric and Subpurpuric Fluence Level of 595-nm Pulsed-Dye Laser for Treatment of Moderate to Severe Acne Vulgaris. AB - BACKGROUND: Various forms of laser therapy including the pulsed-dye laser (PDL) have been reported to reduce acne lesion counts. OBJECTIVE: In this study, the benefits and complications when using a 595-nm PDL for the treatment of acne vulgaris were evaluated when comparing a subpurpuric (low) fluence level with a purpuric (high) fluence level. MATERIALS AND METHODS: This study was a prospective, single-blinded split-face clinical trial. Inclusion criteria included subjects with moderate to severe facial acne. All participants were treated with PDL, with each half of the face receiving either high or low fluence at 3-week intervals for a total of 4 treatments. Standardized facial photographs were obtained and blindly evaluated. RESULTS: Sixty-two subjects were enrolled with a mean age of 22.3 years. Fifty-five patients completed the study. The results showed a significant decrease in lesion counts compared with baseline after all treatments. However, the study did not demonstrate a statistically significant difference between the fluence parameters. The only treatment-related adverse event was temporary hyperpigmentation. CONCLUSION: This study demonstrates that PDL is effective in reducing acne lesions using purpuric and subpurpuric fluences. However, there was no statistically significant difference in acne lesion count between the higher and lower fluences. PMID- 26890803 TI - The experience of discharge for patients with an acquired brain injury from the inpatient to the community setting: A qualitative review. AB - BACKGROUND: Discharge planning for patients with an acquired brain injury (ABI) is considered best practice for assisting the patient and caregiver to successfully transition from hospital to home and is complex because of the long term care and support needs of the patient. This review aimed to describe and synthesize the perspectives of patients with ABI and their family/caregivers on the transition from hospital to home to better understand opportunities to optimize the process. METHODS: Electronic medical databases (n = 5) and grey literature published between January-May 2015 were searched to identify qualitative studies on the experience of transition from the hospital to home setting following ABI. Relevant studies were appraised and narratively synthesized. RESULTS: Nine eligible studies that met the inclusion criteria were identified. Two major themes were identified-Engagement and Support. Three underlying sub-themes-poor communication, limited participation and disorganized arrangements for support services-were identified as key contributors to an unsatisfactory experience for patients and their family/caregivers. CONCLUSION: The transition for patients with an ABI and their family/caregivers was characterized as fragmented and unsatisfactory for supporting a successful return home. This review highlights the importance of tailored education and involvement of the patient and their family/caregiver to increase readiness for returning home and reduce unplanned re-admissions. PMID- 26890804 TI - High Efficiency Photoelectrocatalytic Methanol Oxidation on CdS Quantum Dots Sensitized Pt Electrode. AB - A cadmium sulfide quantum dots sensitized Pt (Pt-CdS) composite was synthesized using a solvothermal method and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance spectroscopy. The catalytic properties of the as-prepared electrode for methanol oxidation were evaluated by cyclic voltammetry (CV), chronoamperometry, electrochemical impedance spectrum (EIS) and photocurrent responses. The as-prepared Pt-CdS electrode displayed a significant enhancement in the electrocatalytic activity and stability for methanol oxidation in the presence of visible light irradiation. The synergistic effect of both the electro and photocatalytic reaction contributes to this enhanced catalytic performance. Our result suggests a new paradigm to construct photoelectrocatalysts with high performance and good stability for direct methanol fuel cells with the assistance of visible-light illumination. PMID- 26890805 TI - Quantitative MR imaging in fracture dating--Initial results. AB - For exact age determinations of bone fractures in a forensic context (e.g. in cases of child abuse) improved knowledge of the time course of the healing process and use of non-invasive modern imaging technology is of high importance. To date, fracture dating is based on radiographic methods by determining the callus status and thereby relying on an expert's experience. As a novel approach, this study aims to investigate the applicability of magnetic resonance imaging (MRI) for bone fracture dating by systematically investigating time-resolved changes in quantitative MR characteristics after a fracture event. Prior to investigating fracture healing in children, adults were examined for this study in order to test the methodology for this application. Altogether, 31 MR examinations in 17 subjects (?: 11 ?: 6; median age 34 +/- 15 y, scanned 1-5 times over a period of up to 200 days after the fracture event) were performed on a clinical 3T MR scanner (TimTrio, Siemens AG, Germany). All subjects were treated conservatively for a fracture in either a long bone or in the collar bone. Both, qualitative and quantitative MR measurements were performed in all subjects. MR sequences for a quantitative measurement of relaxation times T1 and T2 in the fracture gap and musculature were applied. Maps of quantitative MR parameters T1, T2, and magnetisation transfer ratio (MTR) were calculated and evaluated by investigating changes over time in the fractured area by defined ROIs. Additionally, muscle areas were examined as reference regions to validate this approach. Quantitative evaluation of 23 MR data sets (12 test subjects, ?: 7 ?: 5) showed an initial peak in T1 values in the fractured area (T1=1895 +/- 607 ms), which decreased over time to a value of 1094 +/- 182 ms (200 days after the fracture event). T2 values also peaked for early-stage fractures (T2=115 +/- 80 ms) and decreased to 73 +/- 33 ms within 21 days after the fracture event. After that time point, no significant changes could be detected for T2. MTR remained constant at 35.5 +/- 8.0% over time. The study shows that the quantitative assessment of T1 and T2 behaviour over time in the fractured region enable the generation of a novel model allowing for an objective age determination of a fracture. PMID- 26890806 TI - [60]Fullerene-porphyrin [n]pseudorotaxanes: self-assembly, photophysics and third order NLO response. AB - By means of different spectroscopic techniques, we investigate a novel series of porphyrin derivatives (H2TPP), connected to dibenzo-24-crown-8 (DB24C8) moieties, which undergo self-assembly with different methano[60]fullerene units bearing dibenzylammonium (DBA) cations. The formation of both [2] and [3]pseudorotaxanes was proved by means of NMR, UV-Vis-NIR absorption and emission spectroscopies. With the support of molecular modelling studies, spectroscopic investigations showed the presence of a secondary interaction between the porphyrin and the C60 chromophores leading to the formation of different types of "face-to-face" assemblies. Remarkably, investigations of the non-linear optical response of these supramolecular systems showed that individual porphyrin and fullerene derivatives exhibit significantly lower second hyperpolarizability values when compared to their pseudorotaxanes functionalised counterparts. This proves that this class of supramolecular materials possesses relevant NLO response, which strongly depends on the structural arrangement of the chromophores in solution. PMID- 26890807 TI - Association between multidisciplinary team care approach and survival rates in patients with oral cavity squamous cell carcinoma. AB - BACKGROUND: The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC). METHODS: We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC. RESULTS: Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001). CONCLUSION: The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater thoroughness in clinical management. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1544-E1553, 2016. PMID- 26890809 TI - Sonographically detected free appendicolith as a sign of retrocecal perforated appendicitis in a 2-year-old child. AB - Prompt and accurate diagnosis of perforated appendicitis is crucial for proper and timely treatment. The appendix, however, cannot always be identified with sonography (US). We report the case of a 2-year-old child with atypical clinical presentation, and US detection of a free appendicolith as a sign of perforated appendicitis, without visualization of the appendix itself. Laparoscopy revealed a retrocecal, gangrenous, perforated appendix with autoamputation, fibrinopurulent peritonitis, and a free appendicolith within the abdominal fluid. US detection of a free appendicolith in a child is a very rare, but unequivocal sign of perforated appendicitis, which should be sought. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:395-398, 2016. PMID- 26890808 TI - Activation of futile cycles as an approach to increase ethanol yield during glucose fermentation in Saccharomyces cerevisiae. AB - An increase in ethanol yield by yeast from the fermentation of conventional sugars such as glucose and sucrose is possible by reducing the production of a key byproduct such as cellular biomass. Previously we have reported that overexpression of PHO8 gene encoding non-specific ATP-hydrolyzing alkaline phosphatase can lead to a decrease in cellular ATP content and to an increase in ethanol yield during glucose fermentation by Saccharomyces cerevisiae. In this work we further report on 2 new successful approaches to reduce cellular levels of ATP that increase ethanol yield and productivity. The first approach is based on the overexpression of the heterologous Escherichia coli apy gene encoding apyrase or SSB1 part of the chaperon that exhibit ATPase activity in yeast. In the second approach we constructed a futile cycle by the overexpression of S. cerevisiae genes encoding pyruvate carboxylase and phosphoenolpyruvate carboxykinase in S. cerevisiae. These genetically engineered strains accumulated more ethanol compared to the wild-type strain during alcoholic fermentation. PMID- 26890810 TI - Cinnamaldehydes in Cancer Chemotherapy. AB - Cinnamaldehyde and cinnamaldehyde-derived compounds are candidates for the development of anticancer drugs that have received extensive research attention. In this review, we summarize recent findings detailing the positive and negative aspects of cinnamaldehyde and its derivatives as potential anticancer drug candidates. Furthermore, we describe the in vivo pharmacokinetics and metabolism of cinnamaldehydes. The oxidative and antioxidative properties of cinnamaldehydes, which contribute to their potential in chemotherapy, have also been discussed. Moreover, the mechanism(s) by which cinnamaldehydes induce apoptosis in cancer cells have been explored. In addition, evidence of the regulatory effects of cinnamaldehydes on cancer cell invasion and metastasis has been described. Finally, the application of cinnamaldehydes in treating various types of cancer, including breast, prostate, and colon cancers, has been discussed in detail. The effects of cinnamaldehydes on leukemia, hepatocellular carcinoma, and oral cancer have been summarized briefly. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890811 TI - School-Based Interventions to Promote Empathy-Related Responding in Children and Adolescents: A Developmental Analysis. AB - Empathy has been identified as a core component of social and emotional functioning across development. Various prevention and intervention programs have utilized components of empathy-related responding to promote the development of children's and adolescents' social-emotional functioning and impede their aggression in school contexts. In this article, we assess the effectiveness of select school-based empathy interventions and the extent to which they align with developmental theory and research. First, we review current conceptualizations of empathy-related responding, identify its components, outline its normative development, and describe the need for developmentally tailored interventions. We then identify and assess the effectiveness and developmental sensitivity of 19 school-based programs with strong empirical support that target empathy-related responding across childhood and adolescence. Although the majority of these programs showed some degree of developmental differentiation between grades, none considered developmental differences within grades. Commencing interventions earlier in development and targeting higher numbers of empathy-related constructs were, in part, associated with larger effects. We discuss how future research can bridge the gap between basic developmental research and the design of developmentally tailored interventions to promote empathy-related responding. PMID- 26890812 TI - A Retrospective Analysis of the Hemostatic Effect of FloSeal in Patients Undergoing Robot-Assisted Laparoscopic Radical Prostatectomy. AB - BACKGROUND: Perioperative bleeding is a potential complication of robot-assisted laparoscopic radical prostatectomy (RALP) that may worsen outcomes. The role of local hemostatic materials in RALP has not been adequately assessed. We evaluated the hemostatic impact of FloSeal (Baxter International Inc., Fremont, Calif., USA) in RALP. METHODS: A retrospective analysis was performed of 392 consecutive patients with prostate cancer who underwent RALP at our institution between February 2008 and July 2014. The patients were divided into 2 consecutive homogenous groups based on the use of FloSeal. Group A included 200 patients who underwent RALP between February 2008 and May 2011, with hemostasis performed using only traditional techniques. Group B included the remaining 192 patients, who underwent RALP between June 2011 and July 2014 and received FloSeal 5 ml after traditional hemostatic methods. We compared the blood transfusion rate, the differences between immediate postoperative hemoglobin (Hb) and mean postoperative day 1 (POD1) Hb levels, difference between POD1 and least Hb levels and difference between immediate postoperative Hb and least Hb levels. RESULTS: The intraoperative use of FloSeal significantly decreased the blood transfusions rate, from 8.5 to 2.1% (p = 0.004). FloSeal was also associated with significant improvements in the difference between the immediate postoperative Hb and POD1 Hb levels (p = 0.03), mean POD1 Hb and least Hb (p = 0.01) and mean immediate postoperative Hb and least Hb levels (p = 0.034). CONCLUSIONS: In this study, the use of FloSeal improves hemostatic outcomes in patients undergoing RALP compared with traditional hemostatic techniques, without increase of cost. PMID- 26890813 TI - RacA-Mediated ROS Signaling Is Required for Polarized Cell Differentiation in Conidiogenesis of Aspergillus fumigatus. AB - Conidiophore development of fungi belonging to the genus Aspergillus involves dynamic changes in cellular polarity and morphogenesis. Synchronized differentiation of phialides from the subtending conidiophore vesicle is a good example of the transition from isotropic to multi-directional polarized growth. Here we report a small GTPase, RacA, which is essential for reactive oxygen species (ROS) production in the vesicle as well as differentiation of phialides in Aspergillus fumigatus. We found that wild type A. fumigatus accumulates ROS in these conidiophore vesicles and that null mutants of racA did not, resulting in the termination of conidiophore development in this early vesicle stage. Further, we found that stress conditions resulting in atypical ROS accumulation coincide with partial recovery of phialide emergence but not subsequent apical dominance of the phialides in the racA null mutant, suggesting alternative means of ROS generation for the former process that are lacking in the latter. Elongation of phialides was also suppressed by inhibition of NADPH-oxidase activity. Our findings provide not only insights into role of ROS in fungal cell polarity and morphogenesis but also an improved model for the developmental regulatory pathway of conidiogenesis in A. fumigatus. PMID- 26890816 TI - Notes from the Field: Nosocomial Outbreak of Middle East Respiratory Syndrome in a Large Tertiary Care Hospital--Riyadh, Saudi Arabia, 2015. AB - Since the first diagnosis of Middle East respiratory syndrome (MERS) caused by the MERS coronavirus (MERS-CoV) in the Kingdom of Saudi Arabia in 2012, sporadic cases and clusters have occurred throughout the country (1). During June-August, 2015, a large MERS outbreak occurred at King Abulaziz Medical City, a 1,200-bed tertiary-care hospital that includes a 150-bed emergency department that registers 250,000 visits per year. PMID- 26890814 TI - Borrelia persica Infection in Immunocompetent Mice--A New Tool to Study the Infection Kinetics In Vivo. AB - Borrelia persica, a bacterium transmitted by the soft tick Ornithodoros tholozani, causes tick-borne relapsing fever in humans in the Middle East, Central Asia and the Indian peninsula. Immunocompetent C3H/HeOuJ mice were infected intradermally with B. persica at varying doses: 1 x 10(6), 1 x 10(4), 1 x 10(2) and 4 x 10(0) spirochetes/mouse. Subsequently, blood samples were collected and screened for the presence of B. persica DNA. Spirochetes were detected in all mice infected with 1 x 10(6), 1 x 10(4) and 1 x 10(2) borrelia by real-time PCR targeting the flaB gene of the bacterium. Spirochetemia developed with a one- to two-day delay when 1 x 10(4) and 1 x 10(2) borrelia were inoculated. Mice injected with only four organisms were negative in all tests. No clinical signs were observed when infected mice were compared to negative control animals. Organs (heart, spleen, urinary bladder, tarsal joint, skin and brain) were tested for B. persica-specific DNA and cultured for the detection of viable spirochetes. Compiled data show that the target organs of B. persica infections are the brain and the skin. A newly developed serological two-tiered test system (ELISA and western blot) for the detection of murine IgM, IgG and IgA antibody titers against B. persica showed a vigorous antibody response of the mice during infection. In conclusion, the infection model described here for B. persica is a platform for in vivo studies to decipher the so far unexplored survival strategies of this Borrelia species. PMID- 26890815 TI - Plk1 inhibition enhances the efficacy of gemcitabine in human pancreatic cancer. AB - Gemcitabine is the standard-of-care for chemotherapy in patients with pancreatic adenocarcinoma and it can directly incorporate into DNA or inhibit ribonucleotide reductase to prevent DNA replication and, thus, tumor cell growth. Most pancreatic tumors, however, develop resistance to gemcitabine. Polo-like kinase 1 (Plk1), a critical regulator in many cell cycle events, is significantly elevated in human pancreatic cancer. In this study, we show that Plk1 is required for the G1/S transition and that inhibition of Plk1 significantly reduces the DNA synthesis rate in human pancreatic cancer cells. Furthermore, the combined effect of a specific Plk1 inhibitor GSK461364A with gemcitabine was examined. We show that inhibition of Plk1 significantly potentiates the anti-neoplastic activity of gemcitabine in both cultured pancreatic cancer cells and Panc1-derived orthotopic pancreatic cancer xenograft tumors. Overall, our study demonstrates that co targeting Plk1 can significantly enhance the efficacy of gemcitabine, offering a promising new therapeutic option for the treatment of gemcitabine-resistant human pancreatic cancer. PMID- 26890817 TI - Epidemiology of Histoplasmosis Outbreaks, United States, 1938-2013. AB - Histoplasmosis has been described as the most common endemic mycosis in the United States. However, histoplasmosis is not nationally notifiable. Its presumed geographic distribution is largely derived from skin test surveys performed during the 1940s, and information about its local features comes primarily from outbreak investigations. We conducted a literature review to assess epidemiologic features of histoplasmosis outbreaks in the United States. During 1938-2013, a total of 105 outbreaks involving 2,850 cases were reported in 26 states and the territory of Puerto Rico. Common exposure settings were chicken coops and buildings or other structures undergoing renovation or demolition. Birds, bats, or their droppings were reported to be present in 77% of outbreak settings, and workplace exposures were reported in 41% of outbreaks. The continued occurrence of histoplasmosis outbreaks, particularly work-related ones involving known disturbance of bird or bat droppings, highlights the need to increase awareness of the disease. PMID- 26890818 TI - Serum anti-lysozyme is associated with disease activity of Behcet's disease. AB - OBJECTIVES: We investigated the association between autoantibodies against non myeloperoxidase (MPO) neutrophil granule antigens and activity of Behcet's disease (BD). METHODS: We consecutively enrolled 51 BD patients. We assessed clinical data and BD activity using patients' index scores from the Behcet's Disease Current Activity Form and we performed tests for antibodies against proteinase 3 (PR3), MPO, bactericidal permeability increasing protein (BPI), cathepsin G, elastase, lactoferrin and lysozyme. RESULTS: The median patient index score was 2.0, and 56.9% of patients had active BD. In multivariate analysis of variables with significant correlations, only anti-lysozyme showed a significant correlation with BD activity (P = 0.002). In multivariate logistic regression analyses of variables, when patients were classified into groups according to the optimal cutoff levels of erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and anti-lysozyme (ESR > 42.5 mm/h, CRP > 1.35 mg/L and anti-lysozyme > 2.95 IU/mL), the variable with independent predictive value was anti-lysozyme (odds ratio 8.384, P = 0.015). CONCLUSION: Anti-lysozyme was significantly correlated with disease activity score and it was the only independent value to predict active disease in patients with BD. Furthermore, patients having anti-lysozyme levels >= 2.95 IU/mL had a significantly higher risk of having active BD than those who did not. PMID- 26890819 TI - Spontaneous complete resolution of pneumomediastinum and pneumatosis intestinalis caused by acute GVHD. PMID- 26890820 TI - Characterization study on machining PMMA thin-film using AFM tip-based dynamic plowing lithography. AB - This paper presents a reliable nanolithography technique, namely dynamic plowing lithography (DPL) based on a commercial atomic force microscope (AFM). The poly(methyl methacrylate) (PMMA) solution spinning on a silicon substrate is utilized to be scratched directly with an oscillating tip at its resonance frequency. The films with different thickness are obtained by adjusting the concentration of solution and post baked time. A new silicon tip is employed to conduct DPL on PMMA film surface. The geometry of nano-line structure scratched on the film with high adhesion force is shown with a transition process, including total protuberance, protuberance with groove and groove with pile-up. The scratching direction has less influence on the scratched depth of groove, while the shape of pile-up is varied with directions. The depth of groove on thin films is increasing with the drive amplitude until the value of the depth reaches to the threshold value. Moreover, owing to smaller elastic modulus, the film with relatively large thickness could be modified by the tip more easily using this DPL method. SCANNING 38:612-618, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890822 TI - Community-acquired acute kidney injury: A challenge and opportunity for primary care in kidney health. AB - Community-acquired acute kidney injury (CA-AKI) has been found to be a common event in the population. Current incidence estimates are not available, but evaluations of severe elevations in serum creatinine indicate that incidence can be as high as 989 cases per million population in those older than 80 years. Data on risk factors are limited, but older age and higher comorbid illness burden, especially diabetes and cardiovascular disease, seem to be more common in patients who suffer CA-AKI. In addition to being more common than hospital acquired AKI, the long-term sequelae of CA-AKI seem to be just as severe, including renal disease progression and mortality. Efforts to better understand the aetiology of CA-AKI and how ultimately to prevent the development of this condition will need to be taken. In the meantime, a concerted effort by general internists and nephrologists will be needed to prevent CA-AKI in the highest risk patients and thus limit the poor outcomes associated with this entity. PMID- 26890821 TI - Executive function predicts the development of play skills for verbal preschoolers with autism spectrum disorders. AB - Executive function and play skills develop in early childhood and are linked to cognitive and language ability. The present study examined these abilities longitudinally in two groups with autism spectrum disorder-a group with higher initial language (n = 30) and a group with lower initial language ability (n = 36). Among the lower language group, concurrent nonverbal cognitive ability contributed most to individual differences in executive function and play skills. For the higher language group, executive function during preschool significantly predicted play ability at age 6 over and above intelligence, but early play did not predict later executive function. These results suggested that factors related to the development of play and executive function differ for subgroups of children with different language abilities and that early executive function skills may be critical in order for verbal children with autism to develop play. Autism Res 2016, 9: 1274-1284. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc. PMID- 26890824 TI - Ultrasensitive and selective assay of glutathione species in arsenic trioxide treated leukemia HL-60 cell line by molecularly imprinted polymer decorated electrochemical sensors. AB - Herein a pair of molecularly imprinted polymer (MIP) modified electrochemical sensors were reported to detect glutathione (GSH) and glutathione disulfide (GSSG) in arsenic trioxide-treated HL-60 cells. MIP film was in situ synthesized onto electrode surface via electro-polymerization in a facile way. The characteristics of the obtained sensors were investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Both GSH-MIP and GSSG-MIP sensors exhibit the relatively wide linear detection range and low detection limit of 1.33 * 10(-10) M (S/N=3). It is found that N-acetylcysteine and DL homocysteine, the precursors of GSH, show little influence on the detection of glutathione species, nor did the reactants of arsenite and GSH. Such strategies were successfully applied to discriminate GSH and GSSG in cell samples with acceptable recoveries of 92.0-109.1%, and the results are comparable with classic o-phthalaldehyde fluorospectrophotometry. Moreover, the presented sensors allow for easy disclosure of the reversion of malignant phenotype in leukemia cells via glutathione species analysis. PMID- 26890823 TI - An ultrasensitive alloyed near-infrared quinternary quantum dot-molecular beacon nanodiagnostic bioprobe for influenza virus RNA. AB - Conventional techniques used to diagnose influenza virus face several challenges, such as low sensitivity, slow detection, false positive results and misinterpreted data. Hence, diagnostic probes that can offer robust detection qualities, such as high sensitivity, rapid detection, elimination of false positive data, and specificity for influenza virus, are urgently needed. The near infrared (NIR) range is an attractive spectral window due to low photon absorption by biological tissues, hence well-constructed fluorescent biosensors that emit within the NIR window can offer an improved limit of detection (LOD). Here, we demonstrate the use of a newly synthesized NIR quinternary alloyed CdZnSeTeS quantum dots (QDs) as an ultrasensitive fluorescence reporter in a conjugated molecular beacon (MB) assay to detect extremely low concentrations of influenza virus H1N1 RNA. Under optimum conditions, two different strains of influenza virus H1N1 RNA were detected based on fluorescence enhancement signal transduction. We successfully discriminated between two different strains of influenza virus H1N1 RNA based on the number of complementary nucleotide base pairs of the MB to the target RNA sequence. The merits of our bioprobe system are rapid detection, high sensitivity (detects H1N1 viral RNA down to 2 copies/mL), specificity and versatility (detects H1N1 viral RNA in human serum). For comparison, a conventional CdSe/ZnS-MB probe could not detect the extremely low concentrations of H1N1 viral RNA detected by our NIR alloyed CdZnSeTeS-MB probe. Our bioprobe detection system produced a LOD as low as ~1 copy/mL and is more sensitive than conventional molecular tests and rapid influenza detection tests (RIDTS) probes. PMID- 26890826 TI - TiO2 decorated Co3O4 acicular nanotube arrays and its application as a non enzymatic glucose sensor. AB - TiO2 modified Co3O4 acicular nanotube arrays (ANTAs) have been fabricated in this study, showing a good performance in glucose detection. In the experiment, the precursor Co(CO3)0.5(OH).0.11H2O acicular nanowire arrays (ANWAs) was first grown on the fluorine doped tin oxide (FTO) substrate by a hydrothermal method. Thereafter, the uniform pink precursor Co(CO3)0.5(OH).0.11H2O ANWAs was completely converted to the black Co3O4 ANTAs thin film by alkaline treatment. After the decoration of TiO2, the TiO2/Co3O4 ANTAs electrode exhibits a much higher current response to glucose compared with the Co3O4 ANTAs. Importantly, this neotype composite structure of Co3O4 enhances the glucose sensing performance by increasing specific surface area, additional reactive sites and synergistic effect, which make the TiO2/Co3O4 glucose sensor show a high sensitivity of 2008.82 MUA mM(-1) cm(-2), a fast response time (less than 5s) and a detection limit as low as 0.3396 MUM (S/N=3). The TiO2/Co3O4 ANTAs modified electrode exhibits a high selectivity for glucose in human serum, against ascorbic acid and uric acid. PMID- 26890825 TI - Recent advances in biosensor based diagnosis of urinary tract infection. AB - Urinary tract infections (UTIs) are potentially life threatening infections that are associated with high rates of incidence, recurrence and mortality. UTIs are characterized by several chronic infections which may lead to lethal consequences if left undiagnosed and untreated. The uropathogens are consistent across the globe. The most prevalent uropathogenic gram negative bacteria are Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Klebsiella pneumonia. Early detection and precise diagnosis of these infections will play a pivotal role in health care, pharmacological and biomedical sectors. A number of detection methods are available but their performances are not upto the mark. Therefore a more rapid, selective and highly sensitive technique for the detection and quantification of uropathogen levels in extremely minute concentrations need of the time. This review brings all the major concerns of UTI at one's doorstep such as clinical costs and incidence rate, several diagnostic approaches along with their advantages and disadvantages. Paying attention to detection approaches with emphasizing biosensor based recent developments in the quest for new diagnostics for UTI and the need for more sophisticated techniques in terms of selectivity and sensitivity is discussed. PMID- 26890827 TI - Pegylated folate and peptide-decorated graphene oxide nanovehicle for in vivo targeted delivery of anticancer drugs and therapeutic self-monitoring. AB - This work reports a graphene oxide-based nanovehicle with conjugation of pegylated folate for targeted delivery of anticancer drugs and fluorescein labeled peptide for therapeutic self-monitoring in vitro and in vivo. The nanovehicle could absorb hydrophobic and aromatic drug molecules with high loading capacity and efficiency of more than 1.7 mg mg(-1) and 90%, respectively. MTT and flow cytometric assays demonstrated that the drug-loaded nanovehicle could specifically transport and release the drugs into the folate receptor high expressed cancer cells, which ensured a high therapeutic efficiency to cancer cells and prevented the injury to normal cells. Moreover, confocal fluorescence imaging confirmed that the drug-induced cancer cell death could be visualized with the light-up fluorescence of fluorescein activated by caspase-3. The targeted delivery of drug and self-evaluation of therapeutic efficacy were further successfully realized by living imaging in tumor-bearing mice, which broaden the applications of this theranostic system in vivo and may offer new opportunities for precise cancer treatment. PMID- 26890828 TI - A novel aptasensor for electrochemical detection of ractopamine, clenbuterol, salbutamol, phenylethanolamine and procaterol. AB - beta-agonists are phenylethanolamines with different substituent groups on the aromatic ring and the terminal amino group which have the effect of nutrition redistribution and can accumulate in body tissues causing acute or chronic poisoning when consumed. Therefore, it is very important to establish a fast screening method for the detection of several kinds of beta-agonists in food safety control. In this study, the aptamer-agonists (AP-Ago) has screened out by Isothermal Titration Calorimetric method. AP-Ago was a single-strand DNA with 22 base-pairs. The dissociation constant (Kd) to phenylethanolamine (PHL) was 3.34 * 10(-5)mol L(-1). The AP-Ago based electrode was constructed by self-assembling on gold electrode. A label-free electrochemical aptasensor was then developed with AP-Ago-based gold electrode, which was sensitive to phenylethanolamine(PHL), clenbuterol (CLB), ractopamine (RAC), salbutamol (SAL) and procaterol (PRO). The detection limits were 0.04 ng/mL (RAC), 0.35 pg/mL (CLB), 1.0 pg/mL (PHL), 0.53 pg/mL (SAL) and 1.73 pg/mL(PRO), respectively, The detection time was 15 min. The reproductivity of the mentioned aptasensor is good with RSD of 2.09%. Comparing with ELISA and HPLC on beta-agonists detection in actual sample, this aptasensor is advantage of fewer steps and fast screen-detection of these five beta-agonists or their mixtures. This study suggests that the aptasensor can be developed to a rapid screening means with multi-beta-agonists (may be one or more) in sample. PMID- 26890829 TI - Addendum: Stem cell therapy in postinfarction chronic coronary heart disease. PMID- 26890832 TI - Surgery and senescence. PMID- 26890834 TI - Frailty and cognitive impairment: Unique challenges in the older emergency surgical patient. AB - INTRODUCTION: Older patients (>65 years of age) admitted as general surgical emergencies increasingly require improved recognition of their specific needs relative to younger patients. Two such needs are frailty and cognitive impairment. These are evolving research areas that the emergency surgeon increasingly requires knowledge of to improve short- and long-term patient outcomes. METHODS: This paper reviews the evidence for frailty and cognitive impairment in the acute surgical setting by defining frailty and cognitive impairment, introducing methods of diagnosis, discussing the influence on prognosis and proposing strategies to improve older patient outcomes. RESULTS: Frailty is present in 25% of the older surgical population. Using frailty-scoring tools, frailty was associated with a significantly longer hospital stay and higher mortality at 30 and 90 days after admission to an acute surgical unit. Cognitive impairment is present in a high number of older acute surgical patients (approximately 70%), whilst acute onset cognitive impairment, termed delirium, is documented in 18%. However, patients with delirium had significantly longer hospital stays and higher in-hospital mortality than those with cognitive impairment. CONCLUSIONS: Improved knowledge of frailty and delirium by the emergency surgeon allows the specialised needs of older surgical patients to be taken into account. Early recognition, and consideration of minimally invasive surgery or radiological intervention alongside potentially transferable successful elective interventions such as comprehensive geriatric assessment, may help to improve short- and long-term patient outcomes in this vulnerable population. PMID- 26890830 TI - Safety and technique of ferumoxytol administration for MRI. AB - Ferumoxytol is an ultrasmall superparamagnetic iron oxide agent marketed for the treatment of anemia. There has been increasing interest in its properties as an MRI contrast agent as well as greater awareness of its adverse event profile. This mini-review summarizes the current state of knowledge of the risks of ferumoxytol and methods of administration. PMID- 26890835 TI - Knee surgery and its evidence base. AB - INTRODUCTION: Evidence driven orthopaedics is gaining prominence. It enables better management decisions and therefore better patient care. The aim of our study was to review a selection of the leading publications pertaining to knee surgery to assess changes in levels of evidence over a decade. METHODS: Articles from the years 2000 and 2010 in The Knee, the Journal of Arthroplasty, Knee Surgery, Sports Traumatology, Arthroscopy, the Journal of Bone and Joint Surgery (American Volume) and the Bone and Joint Journal were analysed and ranked according to guidelines from the Centre for Evidence-Based Medicine. The intervening years (2003, 2005 and 2007) were also analysed to further define the trend. RESULTS: The percentage of high level evidence (level I and II) studies increased albeit without reaching statistical significance. Following a significant downward trend, the latter part of the decade saw a major rise in levels of published evidence. The most frequent type of study was therapeutic. CONCLUSIONS: Although the rise in levels of evidence across the decade was not statistically significant, there was a significant drop and then rise in these levels in the interim. It is therefore important that a further study is performed to assess longer-term trends. Recent developments have made clear that high quality evidence will be having an ever increasing influence on future orthopaedic practice. We suggest that journals implement compulsory declaration of a published study's level of evidence and that authors consider their study designs carefully to enhance the quality of available evidence. PMID- 26890836 TI - Safe management of paediatric penetrating head injury without a CT scanner: A strategy for humanitarian surgeons based on experience in southern Afghanistan. AB - INTRODUCTION: In many parts of the world, access to a CT scanner remains almost non-existent, and patients with a head injury are managed expectantly, often with poor results. Recent military medical experience in southern Afghanistan using a well-equipped surgical facility with a CT scanner has provided new insights into safe surgical practice in resource-poor environments. METHODS: All cases of children aged under 16 years with penetrating head injury who were treated in a trauma unit in southern Afghanistan by a single neurosurgeon between 2008 and 2010 were reviewed. Based on a previously published retrospective review, a clinical strategy aimed specifically at generalist surgeons is proposed for selecting children who can benefit from surgical intervention in environments with no access to CT scanners. RESULTS: Fourteen patients were reviewed, of whom three had a tangential wound, 10 had a penetrating wound with retained fragments and one had a perforating injury. Two operations for generalist surgeons are described in detail: limited wound excision; and simple decompression of the intra-cranial compartment without brain resection or dural repair. CONCLUSIONS: In resource-poor environments, clinically-based criteria may be used as a safe and appropriate strategy for selecting children who may benefit from relatively straightforward surgery after penetrating brain injury. PMID- 26890837 TI - Elastofibroma dorsi: The clunking tumour that need not cause alarm. AB - INTRODUCTION: Elastofibromas are rare, pseudo-tumours arising at the inferior pole of the scapula that have a characteristic presentation. Due to their tissue of origin and size, they may often be mistaken for soft tissue sarcomas. We present the management of patients diagnosed with elastofibroma at a single institution. METHODS: Patients diagnosed with elastofibroma between January 1995 and January 2015 were identified from a prospectively maintained histopathology database. Electronic patient records, imaging and pathology reports were retrieved and reviewed. RESULTS: Thirty seven patients were identified, with a median age of 66 years and a male-to-female ratio of 1:1.6. All tumours occurred in the characteristic subscapular location. The median maximum tumour diameter was 8.2 cm. A synchronous contralateral lesion (15.8%) was found in six patients. Cross-sectional imaging was performed in 29 patients, with magnetic resonance imaging the most common modality (59.5%). Diagnosis was confirmed with percutaneous biopsy in all but one patient, who proceeded directly to surgery. Eighteen patients were managed non-operatively; 19 opted for surgical excision due to significant symptoms. Excision was performed in a marginal fashion and, at a median follow-up of 5 months, no functional impairment or local recurrences were observed. CONCLUSIONS: Soft tissue masses greater than 5 cm in diameter should prompt the clinician to exclude soft tissue sarcoma. The diagnosis of elastofibroma may be alluded to by its typical presentation and can be confirmed by percutaneous biopsy. After excluding malignancy, these lesions can be safely managed non-operatively, with surgery reserved for symptomatic patients. PMID- 26890838 TI - Cost implications and oncological outcomes for laparoscopic versus open surgery for right hemicolectomy. AB - INTRODUCTION: Recent studies have suggested that laparoscopic surgery for colorectal resection confers a cost benefit compared with open surgery. These studies have considered a wide range of colorectal operations together rather than focusing on a single procedure. Our study compared direct clinical costs for laparoscopic versus open right hemicolectomy. METHODS: Clinicopathological data and cost of treatment for all patients who underwent a right hemicolectomy between 2012 and 2013 were collected. The primary outcome was total cost of treatment. Secondary outcomes were length of stay, operative time and morbidity. The minimum follow-up duration was 12 months. Costs for laparoscopic and open surgery for elective resection alone were compared. Further analyses were performed comparing emergency cases with elective cases and cancer with non cancer cases. RESULTS: There were 83 patients who underwent a right hemicolectomy during the study period and of these, 65 had an elective procedure. The total cost of a laparoscopic procedure was L3,998.12 compared with L3,427.50 for open surgery (p=0.039). The length of stay was shorter for laparoscopic surgery while the cost of an emergency right hemicolectomy was significantly greater than for elective surgery. CONCLUSIONS: Although the length of stay for laparoscopic surgery was shorter, this did not translate to a reduction in cost. The cost benefit from a shorter length of stay was offset by a greater cost of consumables. Cost effectiveness analyses should be designed carefully, and they should consider individual operations separately when making healthcare management and funding decisions. PMID- 26890839 TI - Colorectal cancer outcomes in patients aged over 85 years. AB - INTRODUCTION: The prevalence of colorectal cancer is increasing in the elderly. We examined the treatment and outcomes in our institution of patients aged over 85 years with proven colorectal adenocarcinoma. METHODS: One hundred and five patients were identified and stratified by treatment received: curative surgery (CS), other treatments (OT) or best supportive care (BSC). Data on demographics, staging, treatment and survival was collected and analysed. RESULTS: Forty two patients received CS, 36 OT and 27 BSC. While the treated groups (CS and OT) were similar in terms of age (p=0.35) and staging (p=0.16), BSC patients were significantly older and had higher stage disease (p<0.01). Survival was significantly poorer among BSC patients, at a mean of 9.7 months (95% confidence interval [CI] 4.7-14.7) versus 41.6 months (95% CI 32.5-50.7) and OT 27.3 months (95% CI 20.4-34.1) for the CS and OT groups (p<0.001). There was no significant survival difference between CS and OT groups within 2 years of treatment (p=0.12). Thereafter, OT patients had a very similar 5-year survival to that of the BSC group, at 13% versus 43% in CS patients (p<0.001). CONCLUSIONS: These data suggest that, up to 2 years following treatment, the risks of resectional surgery for colorectal cancer may neutralise any benefit. However, those that survive beyond this period show improvements. The challenge of improving patient selection is most acute in the growing ageing population, and highlights the current focus on presenting all treatment options to 'a reasonable patient'. PMID- 26890840 TI - Digging a little deeper: A technical tip to improve intraoperative sampling in prosthetic joint infection. PMID- 26890841 TI - A novel method for delivery of tumescent solution prior to coronal flap incisions. PMID- 26890842 TI - Sharing CT images via smartphone video. PMID- 26890843 TI - Use of the British National Formulary to measure limb length discrepancies in the paediatric outpatient setting. PMID- 26890845 TI - Lactate and adrenergic signalling in trauma. PMID- 26890846 TI - Gastrointestinal clear cell sarcoma-like tumour of the ascending colon. AB - INTRODUCTION: A clear cell sarcoma-like gastrointestinal tumour (CCSLGT) is a rare malignant soft tissue sarcoma. In the literature, they are sometimes referred to as malignant gastrointestinal neuroectodermal tumours, clear cell sarcomas or osteoclast rich tumours of the gastrointestinal tract. CASE HISTORY: We present a case of a CCSLGT arising from the ascending colon of a previously well 22-year-old man presenting with abdominal pain and anaemia. Computed tomography of the abdomen and pelvis showed a 7 cm irregular mass in the right flank that seemed to emerge from the proximal transverse colon. A laparoscopic right hemicolectomy was undertaken to remove the mass. Microscopic pathological examination of the specimen revealed sections of spindle to oval cells with monomorphic nuclei and scant cytoplasm. The cells were arranged in a striking perivascular growth pattern with microcytic breakdown and pseudopapillary formation. Immunohistochemistry analysis showed that the tumour cells removed expressed S100 protein, and were negative for smooth muscle actin, desmin, CD34, CD117, DOG1, HMB-45 and MNF116. Additionally, cytogenetic testing identified EWSR1 gene rearrangement, which was observed by interphase fluorescence in situ hybridisation. CONCLUSIONS: A complex tumour, a CCSLGT can be thought of in simple terms as a gastrointestinal tract tumour that is S100 protein positive, osteoclast rich, HMB-45 negative and compromises a t(12;22)(q13;q12) gene translocation. These simplified CCSLGT characteristics seem to be described and classified under different aliases in the literature, which makes it difficult to accurately predict the appropriate diagnostic and therapeutic modality required to provide the best clinical care. Given that this case report describes the fourth CCSLGT of primary colonic origins, it may aid future targeted therapies as well as offering epidemiological evidence on prevalence and prognosis. PMID- 26890847 TI - An unusual case of an oesophageal foreign body presenting as torticollis. AB - Oesophageal foreign bodies (FBs) are commonly encountered in an otolaryngology setting. The majority of such cases remain in the paediatric population, where obtaining an accurate history of events is challenging. Oesophageal FBs present in a variety of ways other than dysphagia, which may result in delayed presentation, diagnosis and subsequent treatment. Where an ingested FB is a battery, early removal is advocated owing to the potential for significant complications, a problem highlighted by a patient safety alert issued by NHS England. A common paediatric presentation, torticollis has a multitude of potential underlying causes. We present an unusual case of torticollis in a two year old girl, subsequently revealed to be caused by an ingested button battery. PMID- 26890848 TI - An expanding forearm phlegmon and subsequent compartment syndrome. AB - We present the case of a young, fit woman who developed a forearm phlegmon with subsequent compartment syndrome. Further investigation found her to be suffering from endocarditis and she had had recent dental work. Presentation and management is discussed, with learning points highlighted. PMID- 26890849 TI - Retrograde jejunogastric intussusception due to suture concretion. AB - We describe a patient who presented with acute small bowel obstruction five years after Roux-en-Y reconstruction. Computed tomography and operative exploration showed a retrograde intussusception at the gastrojejunostomy due to an intraluminal suture concretion. We describe the preoperative imaging, endoscopic and intraoperative findings, and review the literature. PMID- 26890850 TI - Non-small cell lung cancer with distal cutaneous metastases in a patient with a previously treated colorectal carcinoma. AB - Cutaneous manifestations of visceral carcinomas are scarce, occurring in around 0.7-12% of internal malignancies. Lung cancer is one of the most common sources of skin metastasis, particularly in male patients. We present a case of cutaneous metastasis in a man with concurrent lung lesions and a previously treated colorectal carcinoma. Immunohistochemistry markers for both skin and lung lesions were strongly positive for carcinoembryonic antigen and cytokeratin 20, suggesting an intestinal primary tumour. However, colonoscopy excluded new and metastatic bowel lesions. After multidisciplinary team meetings, which reviewed the clinical, radiological and immunohistochemistry findings, it was concluded to be a non-small cell lung cancer with skin metastasis. This case presented an interesting diagnostic challenge, and highlighted the importance of cross specialty liaison and investigation to reach the correct diagnosis. PMID- 26890851 TI - Late metastatic colon cancer masquerading as primary jejunal carcinoma. AB - Metastasis to the small bowel from a previously resected colorectal cancer is rare and may erroneously be diagnosed as a primary small bowel carcinoma. It usually occurs several years after the primary resection. We present the case of a 67-year-old man who had undergone left hemicolectomy for colon cancer 3 years earlier and returned with subacute small bowel obstruction. This was initially thought, based on preoperative radiological findings and normal colonoscopic examination, to be due a primary jejunal cancer. Even at surgery, the lesion convincingly appeared as an obstructing primary small bowel carcinoma. However, the histology of the resected small bowel revealed metastatic colon cancer. This rare and an unusual metastatic occurrence some years after the primary resection is described and reviewed. PMID- 26890852 TI - Localized peritoneal carcinomatosis mimicking an irreducible left inguinal hernia. AB - Perforated colonic cancers are not rare and leave patients at risk of developing peritoneal carcinomatosis. We present a 68-year-old male patient with a perforated transverse colonic tumour who underwent emergency extended right hemicolectomy. He made an uneventful postoperative recovery, and received adjuvant chemotherapy. Unfortunately, a routine positron emission tomography computed tomography scan 16 months later demonstrated an fluorodeoxyglucose-avid nodule in the left scrotum associated with an irreducible left inguinal hernia that contained sigmoid colon. At laparotomy, the discovery of isolated peritoneal recurrence in the hernia sac was unexpected, given the absence of local recurrence in the region of the original transverse colon cancer perforation. The etiology therefore remains uncertain, but one may speculate that cell implantation occurred within the hernia sac at the initial emergency laparotomy. PMID- 26890853 TI - Tuning Cellular Uptake of Molecular Probes by Rational Design of Their Assembly into Supramolecular Nanoprobes. AB - Intracellular sensing of pathologically relevant biomolecules could provide essential information for accurate evaluation of disease staging and progression, yet the poor cellular uptake of water-soluble molecular probes limits their use as protease sensors. In other cases such as extracellular sensing, cellular uptake should be effectively inhibited. Self-assembly of molecular probes into supramolecular nanoprobes presents a potential strategy to alter their interaction mechanisms with cells to promote or reduce their cellular uptake. Here, we report on the design, synthesis, and assembly of peptide-based molecular beacons into supramolecular protease sensors of either spherical or filamentous shapes. We found that positively charged spherical nanobeacons demonstrate much higher cellular uptake efficiency than its monomeric form, thus making them most suitable for intracellular sensing of the lysosomal protease cathepsin B. Our results also suggest that assembly into filamentous nanobeacons significantly reduces their internalization by cancer cells, an important property that can be utilized for probing extracellular protease activities. These studies provide important guiding principles for rational design of supramolecular nanoprobes with tunable cellular uptake characteristics. PMID- 26890855 TI - Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty Chemicals Manufacturing. AB - The recent uptake of molecular metathesis catalysts in specialty-chemicals and pharmaceutical manufacturing is reviewed. PMID- 26890854 TI - Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening. AB - We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing. PMID- 26890857 TI - Clinical Characteristics and Renal Histology in Pediatric Patients with Hypertension and Prehypertension Secondary to IgA Nephropathy. AB - BACKGROUND/AIM: It has been shown that hypertension (HT) and prehypertension (Pre HT) are associated with increased cardiovascular risk. However, the significance of secondary HT/Pre-HT in children with IgA nephropathy (IgAN) is uncertain. This study aimed to examine the clinical and histopathological features of pediatric patients with HT/Pre-HT. METHODS: Data on children with IgAN from a single Chinese nephrology center were retrospectively reviewed. Morphological changes were evaluated using the Oxford classification, parameters including crescents, glomerular activity index, glomerular chronicity index (GCI), arterial lesions and Lee's grading. The clinical and pathological features were compared according to the occurrence of HT/Pre-HT. RESULTS: One hundred and eight previously untreated children with IgAN were included. HT/Pre-HT was present in 19.44% of children. Children with HT/Pre-HT were older (14.67 +/- 2.37 vs. 12.07 +/- 2.94 years, p < 0.01) and had higher uric acid (380.62 vs. 301.68 MUmol/l, p < 0.01) and lower estimated glomerular filtration rate (eGFR; 89.95 vs. 111.84 ml/min/1.73 m2, p < 0.01). These children also had a higher proportion of segmental glomerulosclerosis or adhesion, GCI, tubular atrophy/interstitial fibrosis and arteriole wall thickening (all p < 0.05). Blood pressure (BP) values were significantly correlated with eGFR, uric acid, segmental glomerulosclerosis or adhesion, tubular atrophy/interstitial fibrosis and arteriole wall thickening (all p < 0.05). In particular, serum uric acid levels had a stronger association with systolic BP (r = 0.434, p < 0.01). CONCLUSION: Our results show that elevated serum uric acid level might be a marker of HT/Pre-HT. In renal histology, chronic lesions were more severe and prevalent in patients with HT/Pre HT than in those without HT/Pre-HT. PMID- 26890856 TI - A novel dual lock method for down-regulation of genes, in which a target mRNA is captured at 2 independent positions by linked locked nucleic acid antisense oligonucleotides. AB - Nuclear factor kappaB (NFkappaB), which is composed of the RelA and p50 subunits, binds to NFkappaB response elements (NREs) and stimulates the transcription of inflammation-related genes. Here, locked nucleic acid (LNA) antisense oligonucleotides (ASOs) complementary to the termini of the 3'- and 5' untranslated regions (UTRs) of the RelA mRNA were generated; these molecules were named 3'-LNA and 5'-LNA, respectively. To evaluate their effects on NFkappaB activity, HeLa cells were co-transfected with the LNA ASOs and a luciferase reporter gene carrying an NRE. Transfection of the cells with 3'-LNA reduced NFkappaB activity by 30-40%, without affecting RelA mRNA accumulation. Concomitant transfection of HeLa cells with 5'-LNA and 3'-LNA resulted in a 70% reduction in NFkappaB activity. Furthermore, partial poly(A) tail shortening occurred in LNA ASO-transfected cells. We also employed triethylene glycol as a spacer to link 5'-LNA and 3'-LNA. Reporter gene assays showed that the spacer linked LNA ASO reduced NFkappaB activity similarly to a combination of 5'-LNA and 3'-LNA. In addition, an in vitro translation assay revealed that spacer-linked LNA ASOs inhibited the translation of a target mRNA in a specific manner. In summary, this study describes a novel antisense method capturing the target mRNA at independent positions. PMID- 26890859 TI - Royal Australian Chemical Institute Awards: C. Yu, J. G. Shapter, and C. J. Jackson / Wilhelm Manchot Research Professorship: M. G. Kanatzidis. PMID- 26890858 TI - The impact of broader regional sharing of livers: 2-year results of "Share 35". AB - In June of 2013, the Organ Procurement and Transplantation Network (OPTN) implemented regional sharing for Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) candidates with scores reaching 35 and above ("Share 35"). The goal of this distribution change was to increase access to lifesaving transplants for the sickest candidates with chronic liver disease and to reduce the waiting-list mortality for this medically urgent group of patients. To assess the impact of this change, we compared results before and after policy implementation at 2 years. Overall, there were more liver transplants performed under Share 35 and a greater percentage of MELD/PELD 35+ candidates underwent transplantation; waiting-list mortality rates in this group were also significantly lower in the post-policy period. Overall adjusted waiting list mortality was decreased slightly, with no significant changes in mortality by age group or ethnicity. Posttransplant graft and patient survival was unchanged overall and was unchanged for the MELD/PELD 35+ recipients. In conclusion, these data demonstrate that the Share 35 policy achieved its goal of increasing access to transplants for these medically urgent patients without reducing access to liver transplants for pediatric and minority candidates. Although the variance in the median MELD at transplant as well as the variance in transport distance increased, there was a decrease in overall liver discard rates and no change in overall cold ischemia times following broader sharing of these organs. The OPTN will continue to monitor this policy, particularly for longer term posttransplant survival outcomes. PMID- 26890860 TI - Extra and Intramuscular Distribution of the Thoracodorsal Nerve with Regard to Nerve Reconstruction Surgeries. AB - Background The lateral branch of the thoracodorsal nerve (LBTN) is used for nerve transfer in facial, musculocutaneous, axillary nerve injuries and for irreparable C5, C6 spinal nerve lesions and accessory nerve defects. For a successful surgical outcome, the nerve to be used in nerve transfer should be of adequate length and thickness for nerve coaptation. Aim Our objective was to evaluate the length of the LBTN that could be obtained as a donor nerve, externally and within the muscle. Method Eight (8) cadavers with intact upper limbs and thorax which could be positioned in the anatomical position were selected for the study. Cadavers with dissected axillae, brachial plexus or upper limbs were excluded. The thoracodorsal neurovascular bundle was dissected and the number of branches of the thoracodorsal nerve was identified along with its lateral branch. The lateral branch was dissected up to the latissimus dorsi muscle and further intramuscularly. All lengths were measured using a vernier caliper. Results The mean length of the LBTN, up to its first intramuscular branch, is 8.14 cm (range 5.99-12.29 cm). Beyond this, the intramuscular nerve branched further and was of very minute diameter. The mean unbranched intramuscular length of the nerve is 3.36 cm (range 1.3-7.71 cm) which is 41.28% of the total length of the LBTN. Conclusion A significant proportion of the LBTN is found within the latissimus dorsi muscle. This length could potentially be used for direct nerve coaptation by intrafascicular dissection. PMID- 26890865 TI - Multiscale Edge Detection Using a Finite Element Framework for Hexagonal Pixel Based Images. AB - In recent years, the processing of hexagonal pixel-based images has been investigated, and as a result, a number of edge detection algorithms for direct application to such image structures have been developed. We build on this paper by presenting a novel and efficient approach to the design of hexagonal image processing operators using linear basis and test functions within the finite element framework. Development of these scalable first order and Laplacian operators using this approach presents a framework both for obtaining large-scale neighborhood operators in an efficient manner and for obtaining edge maps at different scales by efficient reuse of the seven-point linear operator. We evaluate the accuracy of these proposed operators and compare the algorithmic performance using the efficient linear approach with conventional operator convolution for generating edge maps at different scale levels. PMID- 26890866 TI - Reference View Selection in DIBR-Based Multiview Coding. AB - Augmented reality, interactive navigation in 3D scenes, multiview video, and other emerging multimedia applications require large sets of images, hence larger data volumes and increased resources compared with traditional video services. The significant increase in the number of images in multiview systems leads to new challenging problems in data representation and data transmission to provide high quality of experience on resource-constrained environments. In order to reduce the size of the data, different multiview video compression strategies have been proposed recently. Most of them use the concept of reference or key views that are used to estimate other images when there is high correlation in the data set. In such coding schemes, the two following questions become fundamental: 1) how many reference views have to be chosen for keeping a good reconstruction quality under coding cost constraints? And 2) where to place these key views in the multiview data set? As these questions are largely overlooked in the literature, we study the reference view selection problem and propose an algorithm for the optimal selection of reference views in multiview coding systems. Based on a novel metric that measures the similarity between the views, we formulate an optimization problem for the positioning of the reference views, such that both the distortion of the view reconstruction and the coding rate cost are minimized. We solve this new problem with a shortest path algorithm that determines both the optimal number of reference views and their positions in the image set. We experimentally validate our solution in a practical multiview distributed coding system and in the standardized 3D-HEVC multiview coding scheme. We show that considering the 3D scene geometry in the reference view, positioning problem brings significant rate-distortion improvements and outperforms the traditional coding strategy that simply selects key frames based on the distance between cameras. PMID- 26890863 TI - Identification of the Genome Segments of Bluetongue Virus Serotype 26 (Isolate KUW2010/02) that Restrict Replication in a Culicoides sonorensis Cell Line (KC Cells). AB - Bluetongue virus (BTV) can infect most ruminant species and is usually transmitted by adult, vector-competent biting midges (Culicoides spp.). Infection with BTV can cause severe clinical signs and can be fatal, particularly in naive sheep and some deer species. Although 24 distinct BTV serotypes were recognized for several decades, additional 'types' have recently been identified, including BTV-25 (from Switzerland), BTV-26 (from Kuwait) and BTV-27 from France (Corsica). Although BTV-25 has failed to grow in either insect or mammalian cell cultures, BTV-26 (isolate KUW2010/02), which can be transmitted horizontally between goats in the absence of vector insects, does not replicate in a Culicoides sonorensis cell line (KC cells) but can be propagated in mammalian cells (BSR cells). The BTV genome consists of ten segments of linear dsRNA. Mono-reassortant viruses were generated by reverse-genetics, each one containing a single BTV-26 genome segment in a BTV-1 genetic-background. However, attempts to recover a mono reassortant containing genome-segment 2 (Seg-2) of BTV-26 (encoding VP2), were unsuccessful but a triple-reassortant was successfully generated containing Seg 2, Seg-6 and Seg-7 (encoding VP5 and VP7 respectively) of BTV-26. Reassortants were recovered and most replicated well in mammalian cells (BSR cells). However, mono-reassortants containing Seg-1 or Seg-3 of BTV-26 (encoding VP1, or VP3 respectively) and the triple reassortant failed to replicate, while a mono reassortant containing Seg-7 of BTV-26 only replicated slowly in KC cells. PMID- 26890861 TI - Intermittent drivers anchoring to structural heterogeneities as a major pathophysiological mechanism of human persistent atrial fibrillation. AB - The mechanisms responsible for perpetuation of human persistent atrial fibrillation (AF) are controversial and probably vary between individuals. A wide spectrum of mechanisms have been described in experimental studies, ranging from a single localized stable (focal/reentrant) source, to multiple sources, up to diffuse bi-atrial wavelets. We characterized AF drivers in patients with persistent AF (lasting less than 1 year) using novel high resolution mapping, imaging and modelling approaches with the objective of evaluating their relationship to atrial structural heterogeneities. Using panoramic non-invasive mapping in humans, focal or reentrant sources driving AF waves were identified, originating from multiple distinct regions and exhibiting short lifespans and periodic recurrences in the same locations. The reentrant driver regions harboured long, fractionated electrograms covering most of the fibrillatory cycle lengths with varying beat-to-beat sequences suggestive of unstable trajectories attached to slow conducting heterogeneous tissue. MRI atrial imaging demonstrated that such drivers preferentially clustered at the borders of fibrotic atrial regions. In patient-specific computer simulations, sustained AF was shown to be driven by meandering transitory reentries attached to fibrosis borders expressing specific metrics in density and extent. Finally, random microstructural alterations devoid of cellular electrical changes were modelled, showing that a percolation mechanism could also explain atrial reentries and complex fractionated electrograms. These data from clinical, imaging and computational studies strongly suggest that intermittent and spatially unstable drivers anchoring to structural heterogeneities are a major pathophysiological mechanism in human persistent atrial fibrillation. PMID- 26890864 TI - Comparison of the Performance of Cartomizer Style Electronic Cigarettes from Major Tobacco and Independent Manufacturers. AB - OBJECTIVE: This study compared the performance of 12 brands of cartomizer style electronic cigarettes (EC) using different puffing protocols and measured the concentrations of nicotine in each product. METHODS: Air flow rate, pressure drop, and aerosol absorbance were measured using two different protocols, first 10 puffs and a modified smoke-out protocol. RESULTS: First 10 puff protocol: The air flow rate required to produce aerosol ranged between brands from 4-21 mL/s. Pressure drop was relatively stable within a brand but ranged between brands from 14-71 mmH2O and was much lower than the earlier classic 3-piece models. Absorbance, a measure of aerosol density, was relatively consistent between puffs, but varied between brands. With the modified smoke-out protocol, most brands were puffed until 300 puffs. The pressure drop was relatively stable for all brands except three. Absorbance of the aerosol decreased as the number of puffs increased. Although there was some uniformity in performance within some brands, there was large variation between brands. The labeled and measured nicotine concentrations were within 10% of each other in only 1 out of 10 brands. CONCLUSIONS: Over 10 puffs, the cartomizers all perform similarly within a brand but varied between brands. In smoke-out trials, most brands lasted at least 300 puffs, and performed similarly within brands with respect to pressure drop and absorbance. For five brands, products purchased at different times performed differently. These data show some improvement in performance during evolution of these products, but nevertheless indicate problems with quality control in manufacture. PMID- 26890862 TI - A Micro/Nano Composite for Combination Treatment of Melanoma Lung Metastasis. AB - The successful treatment of malignant disease generally requires the use of multiple therapeutic agents that are coordinated in a spatiotemporal manner to enable synergy. Here, a porous silicon-based micro/nano composite (MNC) that is capable of simultaneously delivering chemotherapeutic agents and small interfering RNA (siRNA) to the lungs following intravenous injection is designed. The pores of the silicon microparticles are loaded with B-Raf proto-oncogene serine/threonine kinase (BRAF) siRNA-containing liposomes, while the surface is conjugated with docetaxel-encapsulated polymeric nanoparticles. The synergistic antitumor effect of the MNC is demonstrated in vitro in melanoma cells and in vivo using a mouse model for melanoma lung metastasis. The MNC displays superior therapeutic efficacy and increased accumulation in metastatic melanoma lesions in the lungs in comparison to combination therapy with liposomes and polymers. The results indicate that the MNC can be used as an effective delivery vehicle for simultaneous enrichment of multiple therapeutic agents in the lungs. PMID- 26890868 TI - Learning Invariant Color Features for Person Reidentification. AB - Matching people across multiple camera views known as person reidentification is a challenging problem due to the change in visual appearance caused by varying lighting conditions. The perceived color of the subject appears to be different under different illuminations. Previous works use color as it is or address these challenges by designing color spaces focusing on a specific cue. In this paper, we propose an approach for learning color patterns from pixels sampled from images across two camera views. The intuition behind this work is that, even though varying lighting conditions across views affect the pixel values of the same color, the final representation of a particular color should be stable and invariant to these variations, i.e., they should be encoded with the same values. We model color feature generation as a learning problem by jointly learning a linear transformation and a dictionary to encode pixel values. We also analyze different photometric invariant color spaces as well as popular color constancy algorithm for person reidentification. Using color as the only cue, we compare our approach with all the photometric invariant color spaces and show superior performance over all of them. Combining with other learned low-level and high level features, we obtain promising results in VIPeR, Person Re-ID 2011, and CAVIAR4REID data sets. PMID- 26890867 TI - Robust Fringe Projection Profilometry via Sparse Representation. AB - In this paper, a robust fringe projection profilometry (FPP) algorithm using the sparse dictionary learning and sparse coding techniques is proposed. When reconstructing the 3D model of objects, traditional FPP systems often fail to perform if the captured fringe images have a complex scene, such as having multiple and occluded objects. It introduces great difficulty to the phase unwrapping process of an FPP system that can result in serious distortion in the final reconstructed 3D model. For the proposed algorithm, it encodes the period order information, which is essential to phase unwrapping, into some texture patterns and embeds them to the projected fringe patterns. When the encoded fringe image is captured, a modified morphological component analysis and a sparse classification procedure are performed to decode and identify the embedded period order information. It is then used to assist the phase unwrapping process to deal with the different artifacts in the fringe images. Experimental results show that the proposed algorithm can significantly improve the robustness of an FPP system. It performs equally well no matter the fringe images have a simple or complex scene, or are affected due to the ambient lighting of the working environment. PMID- 26890870 TI - Robust Visual Tracking via Convolutional Networks Without Training. AB - Deep networks have been successfully applied to visual tracking by learning a generic representation offline from numerous training images. However, the offline training is time-consuming and the learned generic representation may be less discriminative for tracking specific objects. In this paper, we present that, even without offline training with a large amount of auxiliary data, simple two-layer convolutional networks can be powerful enough to learn robust representations for visual tracking. In the first frame, we extract a set of normalized patches from the target region as fixed filters, which integrate a series of adaptive contextual filters surrounding the target to define a set of feature maps in the subsequent frames. These maps measure similarities between each filter and useful local intensity patterns across the target, thereby encoding its local structural information. Furthermore, all the maps together form a global representation, via which the inner geometric layout of the target is also preserved. A simple soft shrinkage method that suppresses noisy values below an adaptive threshold is employed to de-noise the global representation. Our convolutional networks have a lightweight structure and perform favorably against several state-of-the-art methods on the recent tracking benchmark data set with 50 challenging videos. PMID- 26890869 TI - A Diffusion and Clustering-Based Approach for Finding Coherent Motions and Understanding Crowd Scenes. AB - This paper addresses the problem of detecting coherent motions in crowd scenes and presents its two applications in crowd scene understanding: semantic region detection and recurrent activity mining. It processes input motion fields (e.g., optical flow fields) and produces a coherent motion field named thermal energy field. The thermal energy field is able to capture both motion correlation among particles and the motion trends of individual particles, which are helpful to discover coherency among them. We further introduce a two-step clustering process to construct stable semantic regions from the extracted time-varying coherent motions. These semantic regions can be used to recognize pre-defined activities in crowd scenes. Finally, we introduce a cluster-and-merge process, which automatically discovers recurrent activities in crowd scenes by clustering and merging the extracted coherent motions. Experiments on various videos demonstrate the effectiveness of our approach. PMID- 26890871 TI - Automatic Design of Color Filter Arrays in the Frequency Domain. AB - In digital color imaging, the raw image is typically obtained through a single sensor covered by a color filter array (CFA), which allows only one color component to be measured at each pixel. The procedure to reconstruct a full color image from the raw image is known as demosaicking. Since the CFA may cause irreversible visual artifacts, the CFA and the demosaicking algorithm are crucial to the quality of demosaicked images. Fortunately, the design of CFAs in the frequency domain provides a theoretical approach to handling this issue. However, almost all the existing design methods in the frequency domain involve considerable human effort. In this paper, we present a new method to automatically design CFAs in the frequency domain. Our method is based on the frequency structure representation of mosaicked images. We utilize a multi objective optimization approach to propose frequency structure candidates, in which the overlap among the frequency components of images mosaicked with the CFA is minimized. Then, we optimize parameters for each candidate, which is formulated as a constrained optimization problem. We use the alternating direction method to solve it. Our parameter optimization method is applicable to arbitrary frequency structures, including those with conjugate replicas of chrominance components. Experiments on benchmark images confirm the advantage of the proposed method. PMID- 26890872 TI - Weakly Supervised Fine-Grained Categorization With Part-Based Image Representation. AB - In this paper, we propose a fine-grained image categorization system with easy deployment. We do not use any object/part annotation (weakly supervised) in the training or in the testing stage, but only class labels for training images. Fine grained image categorization aims to classify objects with only subtle distinctions (e.g., two breeds of dogs that look alike). Most existing works heavily rely on object/part detectors to build the correspondence between object parts, which require accurate object or object part annotations at least for training images. The need for expensive object annotations prevents the wide usage of these methods. Instead, we propose to generate multi-scale part proposals from object proposals, select useful part proposals, and use them to compute a global image representation for categorization. This is specially designed for the weakly supervised fine-grained categorization task, because useful parts have been shown to play a critical role in existing annotation dependent works, but accurate part detectors are hard to acquire. With the proposed image representation, we can further detect and visualize the key (most discriminative) parts in objects of different classes. In the experiments, the proposed weakly supervised method achieves comparable or better accuracy than the state-of-the-art weakly supervised methods and most existing annotation-dependent methods on three challenging datasets. Its success suggests that it is not always necessary to learn expensive object/part detectors in fine-grained image categorization. PMID- 26890873 TI - Is the suppressive effect of cyproterone acetate on serum anti-Mullerian-hormone levels in women with polycystic ovary syndrome stronger than under oral contraceptive pill? AB - OBJECTIVE: To compare the suppressive effect of anti-androgen therapy by cyproterone acetate (CPA) and by oral contraceptive pill (OCP) on anti-mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) in order to detect a putative direct anti-androgen effect on AMH excess. METHODS: This is a prospective longitudinal study including 58 women with PCOS between January 2010 and April 2014 at the Lille University Hospital. A total of 47 women with clinical hyperandrogenism were treated by CPA (50 mg/d was administered 20 days out of 28) and 11 women with PCOS but without clinical hyperandrogenism received OCP. RESULT(S): Serum AHM levels at baseline were similar in CPA and OCP groups (median [5-95th percentiles]: 60.4 pmol/l [25.1-200.2] versus 58 pmol/l [27.6 100], respectively, p = 0.39). After 3 months of treatment, serum AMH levels decreased significantly by 28% +/- 20% and by 22% +/- 27% in CPA and OCP groups, respectively. The decrease under both treatments was similar (p = 0.48). CONCLUSION(S): That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells. PMID- 26890874 TI - Intelligent task management platform for health care workers. AB - The medical staff in a hospital could benefit from a specialized task management system, considering their high workload covering different patients. This article presents an intelligent task management platform that automatically prioritizes and (re-)assigns tasks to the appropriate caregivers based on the current health care context captured in a continuous care ontology. Moreover, this platform provides the caregivers with a smartphone allowing them to easily view and process their assigned tasks. PMID- 26890875 TI - Dicyanoquinodimethane-substituted benzothiadiazole for efficient small-molecule solar cells. AB - Two unsymmetrical donor-acceptor-acceptor-pi-acceptor type benzothiadiazoles (BTD3 and BTD4) functionalized with tetracyanobutadiene (TCBD) and dicyanoquinodimethane (DCNQ) modules, showing strong absorption in the visible region are reported. The bulk heterojunction solar cells based on BTD4:PC71BM and BTD3:PC71BM based active layers processed with chloroform (CF), thermal annealing and subsequent solvent vapor annealing, i.e. two step annealing (TSA), exhibited PCEs of up to 6.02% and 5.36%, respectively, which is significantly higher than those of the corresponding devices based on the as-cast blend active layer. This enhancement is related to the improvement in exciton dissociation efficiency and more balanced charge transport in the devices based on the active layer processed with TSA treatment. PMID- 26890876 TI - Transition-Metal-Free Biomolecule-Based Flexible Asymmetric Supercapacitors. AB - A transition-metal-free asymmetric supercapacitor (ASC) is successfully fabricated based on an earth-abundant biomass derived redox-active biomolecule, named lawsone. Such an ASC exhibits comparable or even higher energy densities than most of the recently reported transition-metal-based ASCs, and this green ASC generation from renewable resources is promising for addressing current issues of electronic hazard processing, high cost, and unsustainability. PMID- 26890878 TI - Two-Stage Design Method for Enhanced Inductive Energy Transmission with Q Constrained Planar Square Loops. AB - Q-factor constraints are usually imposed on conductor loops employed as proximity range High Frequency Radio Frequency Identification (HF-RFID) reader antennas to ensure adequate data bandwidth. However, pairing such low Q-factor loops in inductive energy transmission links restricts the link transmission performance. The contribution of this paper is to assess the improvement that is reached with a two-stage design method, concerning the transmission performance of a planar square loop relative to an initial design, without compromise to a Q-factor constraint. The first stage of the synthesis flow is analytical in approach, and determines the number and spacing of turns by which coupling between similar paired square loops can be enhanced with low deviation from the Q-factor limit presented by an initial design. The second stage applies full-wave electromagnetic simulations to determine more appropriate turn spacing and widths to match the Q-factor constraint, and achieve improved coupling relative to the initial design. Evaluating the design method in a test scenario yielded a more than 5% increase in link transmission efficiency, as well as an improvement in the link fractional bandwidth by more than 3%, without violating the loop Q factor limit. These transmission performance enhancements are indicative of a potential for modifying proximity HF-RFID reader antennas for efficient inductive energy transfer and data telemetry links. PMID- 26890879 TI - Enhanced Pseudocapacitance in Multicomponent Transition-Metal Oxides by Local Distortion of Oxygen Octahedra. AB - Anomalously high pseudocapacitance of a metal oxide was observed when Ni, Co, and Mn were mixed in a solid solution. Analysis by X-ray absorption near-edge spectroscopy (XANES) identified a wider redox swing of Ni as the origin of the enlarged pseudocapacitance. Ab initio DFT calculations revealed that aliovalent species resulting from the copresence of multiple transition metals can generate permanent local distortions of [NiO6] octahedra. As this type of distortion breaks the degenerate eg level of Ni(2+), the Jahn-Teller lattice instability necessary for the Ni(2+/3+) redox flip can be effectively diminished during charge-discharge, thus resulting in the significantly increased capacitance. Our findings highlight the importance of understanding structure-property correlation related to local structural distortions in improving the performance of pseudocapacitors. PMID- 26890877 TI - Effects of dutasteride on lower urinary tract symptoms: a prospective analysis based on changes in testosterone/dihydrotestosterone levels and total prostatic volume reduction. AB - This study analyzed the effects of dutasteride on lower urinary tract symptoms based on the association between changes in the total testosterone (TT)/dihydrotestosterone (DHT) levels and total prostate volume (TPV) reduction. Sixty participants diagnosed with benign prostatic hyperplasia were given 0.5 mg of dutasteride daily for 52 weeks. Measures of TT and DHT levels, TPV and uroflowmetry were obtained before and after dutasteride treatment. Forty-three patients demonstrated a TPV reduction of >=5% (Group 1), whereas the remaining 17 patients demonstrated a TPV reduction of <5% (Group 2). DHT suppression and DHT/TT ratio at baseline were significantly higher in Group 1 than Group 2. International Prostate Symptom Scores (IPSS) and uroflowmetry were significantly improved in both groups. In Group 2, nine patients demonstrated some improvement in IPSS (Group 2A), whereas eight did not (Group 2B). The rate of TT increase and improvement in voiding symptoms were significantly higher in Group 2A than Group 2B. Dutasteride-induced TPV reduction is dependent on individual 5-alpha reductase inhibitor activity. Some patients demonstrating smaller dutasteride induced TPV reduction may experience an improvement in voiding symptoms owing to an increased level of testosterone. PMID- 26890880 TI - Adapting content-based image retrieval techniques for the semantic annotation of medical images. AB - The automatic annotation of medical images is a prerequisite for building comprehensive semantic archives that can be used to enhance evidence-based diagnosis, physician education, and biomedical research. Annotation also has important applications in the automatic generation of structured radiology reports. Much of the prior research work has focused on annotating images with properties such as the modality of the image, or the biological system or body region being imaged. However, many challenges remain for the annotation of high level semantic content in medical images (e.g., presence of calcification, vessel obstruction, etc.) due to the difficulty in discovering relationships and associations between low-level image features and high-level semantic concepts. This difficulty is further compounded by the lack of labelled training data. In this paper, we present a method for the automatic semantic annotation of medical images that leverages techniques from content-based image retrieval (CBIR). CBIR is a well-established image search technology that uses quantifiable low-level image features to represent the high-level semantic content depicted in those images. Our method extends CBIR techniques to identify or retrieve a collection of labelled images that have similar low-level features and then uses this collection to determine the best high-level semantic annotations. We demonstrate our annotation method using retrieval via weighted nearest-neighbour retrieval and multi-class classification to show that our approach is viable regardless of the underlying retrieval strategy. We experimentally compared our method with several well-established baseline techniques (classification and regression) and showed that our method achieved the highest accuracy in the annotation of liver computed tomography (CT) images. PMID- 26890881 TI - Unmasking Heavily O-Glycosylated Serum Proteins Using Perchloric Acid: Identification of Serum Proteoglycan 4 and Protease C1 Inhibitor as Molecular Indicators for Screening of Breast Cancer. AB - Heavily glycosylated mucin glycopeptides such as CA 27.29 and CA 15-3 are currently being used as biomarkers for detection and monitoring of breast cancer. However, they are not well detected at the early stages of the cancer. In the present study, perchloric acid (PCA) was used to enhance detection of mucin-type O-glycosylated proteins in the serum in an attempt to identify new biomarkers for early stage breast cancer. Sensitivity and specificity of an earlier developed sandwich enzyme-linked lectin assay were significantly improved with the use of serum PCA isolates. When a pilot case-control study was performed using the serum PCA isolates of normal participants (n = 105) and patients with stage 0 (n = 31) and stage I (n = 48) breast cancer, higher levels of total O-glycosylated proteins in sera of both groups of early stage breast cancer patients compared to the normal control women were demonstrated. Further analysis by gel-based proteomics detected significant inverse altered abundance of proteoglycan 4 and plasma protease C1 inhibitor in both the early stages of breast cancer patients compared to the controls. Our data suggests that the ratio of serum proteoglycan 4 to protease C1 inhibitor may be used for screening of early breast cancer although this requires further validation in clinically representative populations. PMID- 26890884 TI - Adolescent physical activity levels: discrepancies with accelerometer data analysis. AB - This study investigated the effects of epoch length and cut point selection on adolescent physical activity intensity quantification using vertical axis and vector magnitude (VM) measurement with the ActiGraph GT3X+ accelerometer. Four hundred and nine adolescents (211 males; 198 females) aged 12-16 years of age wore accelerometers during waking hours. The GT3X+ acceleration counts were reintegrated into 1, 5, 15, 30 and 60 s epoch lengths for both vertical axis and VM counts. One cut point was applied to vertical axis counts and three different cut points were applied to VM counts for each epoch length. Significant differences (P < 0.01) in mean total counts per day were observed between vertical axis and VM counts, and between epoch lengths for VM only. Differences in physical activity levels were observed between vertical and VM cut points, and between epoch lengths across all activity intensities. Our findings illustrate the magnitude of differences in physical activity outcomes that occur between axis measurement, cut points and epoch length. The magnitude of difference across epoch length must be considered in the interpretation of accelerometer data and seen as a confounding variable when comparing physical activity levels between studies. PMID- 26890882 TI - Illuminating the Prevalence of Trypanosoma brucei s.l. in Glossina Using LAMP as a Tool for Xenomonitoring. AB - BACKGROUND: As the reality of eliminating human African trypanosomiasis (HAT) by 2020 draws closer, the need to detect and identify the remaining areas of transmission increases. Here, we have explored the feasibility of using commercially available LAMP kits, designed to detect the Trypanozoon group of trypanosomes, as a xenomonitoring tool to screen tsetse flies for trypanosomes to be used in future epidemiological surveys. METHODS AND FINDINGS: The DNA extraction method was simplified and worked with the LAMP kits to detect a single positive fly when pooled with 19 negative flies, and the absolute lowest limit of detection that the kits were able to work at was the equivalent of 0.1 trypanosome per ml. The DNA from Trypanosoma brucei brucei could be detected six days after the fly had taken a blood meal containing dead trypanosomes, and when confronted with a range of non-target species, from both laboratory-reared flies and wild-caught flies, the kits showed no evidence of cross-reacting. CONCLUSION: We have shown that it is possible to use a simplified DNA extraction method in conjunction with the pooling of tsetse flies to decrease the time it would take to screen large numbers of flies for the presence of Trypanozoon trypanosomes. The use of commercially-available LAMP kits provides a reliable and highly sensitive tool for xenomonitoring and identifying potential sleeping sickness transmission sites. PMID- 26890883 TI - Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution. AB - Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease. PMID- 26890885 TI - Infliximab Dosing Strategies and Predicted Trough Exposure in Children With Crohn Disease. AB - OBJECTIVES: Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 MUg/mL. METHODS: A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy. RESULTS: Based on the index case of a 10-year-old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (interquartile range) simulated infliximab trough concentration at week 14 was 1.3 (0.5-2.7) MUg/mL and 2.4 (1.0-4.8) MUg/mL for albumin levels of 3 and 4 g/dL, respectively. Among 1000 simulated children in the model, trough concentration >3 MUg/mL at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dL, respectively. CONCLUSIONS: Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy. PMID- 26890887 TI - Canadian Experience with Fingolimod: Adherence to Treatment and Monitoring. AB - BACKGROUND: The Canadian GILENYA(r) Go ProgramTM provides education and support to people with relapsing-remitting multiple sclerosis during fingolimod treatment. METHODS: Data were collected and analyzed from the time of the first individual enrolled in March 2011 to March 31, 2014. Individuals were excluded if they withdrew from the program prior to receiving the first dose, or had not completed the first dose observation (FDO) at the time of data cut-off. Reports of adverse effects were validated with a database of adverse events reported to Novartis Pharmaceuticals Canada Inc. RESULTS: A total of 2,399 individuals had completed FDO at the end of the three-year observation period. Mean age was 41.2 years; 75.2% were female. The most recent prior therapies reported were interferon-beta agents (50.2%), glatiramer acetate (31.1%), natalizumab (14.2%), no prior therapy (3.3%), and other agent (1.1%). Reasons for switching to fingolimod were lack of efficacy (34.9%), side effects (34.6%), and dissatisfaction with injections/infusion (30.4%). Continuation rates with fingolimod at 12, 24 and 30 months were 80.7%, 76.6% and 76.0%, respectively. The discontinuation rate due to reported lack of efficacy during the three-year period was 1.3%. There was 94.4% adherence to the scheduled ophthalmic examination. CONCLUSIONS: The GILENYA(r) Go ProgramTM captures data for virtually all fingolimod-treated patients in Canada, enabling the evaluation of fingolimod use in routine practice. Ongoing patient support and reminders to take the medication, in conjunction with physicians' and/or patients' perception of the efficacy and tolerability of fingolimod, resulted in a high rate of continuation during longer-term therapy. PMID- 26890888 TI - Flip to Regular Triangulation and Convex Hull. AB - Flip is a simple and local operation to transform one triangulation to another. It makes changes only to some neighboring simplices, without considering any attribute or configuration global in nature to the triangulation. Thanks to this characteristic, several flips can be independently applied to different small, non-overlapping regions of one triangulation. Such operation is favored when designing algorithms for data-parallel, massively multithreaded hardware, such as the GPU. However, most existing flip algorithms are designed to be executed sequentially, and usually need some restrictions on the execution order of flips, making them hard to be adapted to parallel computation. In this paper, we present an in depth study of flip algorithms in low dimensions, with the emphasis on the flexibility of their execution order. In particular, we propose a series of provably correct flip algorithms for regular triangulation and convex hull in 2D and 3D, with implementations for both CPUs and GPUs. Our experiment shows that our GPU implementation for constructing these structures from a given point set achieves up to two orders of magnitude of speedup over other popular single threaded CPU implementation of existing algorithms. PMID- 26890886 TI - Tyrosine Hydroxylation in Betalain Pigment Biosynthesis Is Performed by Cytochrome P450 Enzymes in Beets (Beta vulgaris). AB - Yellow and red-violet betalain plant pigments are restricted to several families in the order Caryophyllales, where betacyanins play analogous biological roles to anthocyanins. The initial step in betalain biosynthesis is the hydroxylation of tyrosine to form L-DOPA. Using gene expression experiments in beets, yeast, and Arabidopsis, along with HPLC/MS analysis, the present study shows that two novel cytochrome P450 (CYP450) enzymes, CYP76AD6 and CYP76AD5, and the previously described CYP76AD1 can perform this initial step. Co-expressing these CYP450s with DOPA 4,5-dioxygenase in yeast, and overexpression of these CYP450s in yellow beets show that CYP76AD1 efficiently uses L-DOPA leading to red betacyanins while CYP76AD6 and CYP76AD5 lack this activity. Furthermore, CYP76AD1 can complement yellow beetroots to red while CYP76AD6 and CYP76AD5 cannot. Therefore CYP76AD1 uniquely performs the beet R locus function and beets appear to be genetically redundant for tyrosine hydroxylation. These new functional data and ancestral character state reconstructions indicate that tyrosine hydroxylation alone was the most likely ancestral function of the CYP76AD alpha and beta groups and the ability to convert L-DOPA to cyclo-DOPA evolved later in the alpha group. PMID- 26890889 TI - Reactive Oxygen Species Mediate TNF-x237A; Cytotoxic Effects in the Multidrug Resistant Breast Cancer Cell Line MCF-7/MX. AB - BACKGROUND: Reactive oxygen species (ROS) are not only harmful by-products of the cellular metabolism but also essential components of cell signaling, contributing to various physiologic features including cytokine and growth factor signaling. Here, we examined the role of ROS in the cytotoxic effects of tumor necrosis factor-x237A; (TNF-x237A;) in MCF-7 cells and their drug-resistant counterparts, MCF-7/MX cells. MATERIALS AND METHODS: ROS levels were evaluated following TNF x237A; exposure using 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) as fluorescent probe, and the TNF-x237A; cytotoxic effects were examined using the dimethylthiazolyl-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: TNF x237A; led to ROS accumulation only in MCF-7/MX and not in MCF-7 cells. The role of ROS in the cytotoxic effects of TNF-x237A; was further evaluated by inhibition of ROS accumulation in MCF-7/MX cells and by induction of ROS generation in MCF-7 cells along with TNF-x237A; treatment. ROS accumulation sensitized the MCF-7 cells to the cytotoxic effects of TNF-x237A; while inhibition of ROS accumulation attenuated the cytotoxic effects of TNF-x237A; in MCF-7/MX cells. Following TNF x237A; treatment, the activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase) were evaluated in both cell lines. The results of the enzyme assays revealed that superoxide dismutase activity was enhanced in MCF-7 but not in MCF-7/MX cells. CONCLUSIONS: ROS accumulation in MCF-7/MX cells may be involved in the higher cytotoxic effects of TNF-x237A; in the MCF-7/MX cell line. PMID- 26890890 TI - Development of a Northern Continental Air Standard Reference Material. AB - The National Institute of Standards and Technology (NIST) recently began to develop standard mixtures of greenhouse gases as part of a broad program mandated by the 2009 United States Congress to support research in climate change. To this end, NIST developed suites of gravimetrically assigned primary standard mixtures (PSMs) comprising carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) in a dry-natural air balance at ambient mole fraction levels. In parallel, the National Oceanic and Atmospheric Administration (NOAA) in Boulder, Colorado, charged 30 aluminum gas cylinders with northern hemisphere air at Niwot Ridge, Colorado. These mixtures, which constitute NIST Standard Reference Material (SRM) 1720 Northern Continental Air, were certified by NIST for ambient mole fractions of CO2, CH4, and N2O relative to NIST PSMs. NOAA-assigned values are also provided as information in support of the World Meteorological Organization (WMO) Global Atmosphere Watch (GAW) Program for CO2, CH4, and N2O, since NOAA serves as the WMO Central Calibration Laboratory (CCL) for CO2, CH4, and N2O. Relative expanded uncertainties at the 95% confidence interval are <+/-0.06% of the certified values for CO2 and N2O and <0.2% for CH4, which represents the smallest relative uncertainties specified to date for a gaseous SRM produced by NIST. Agreement between the NOAA (WMO/GAW) and NIST values based on their respective calibration standards suites is within 0.05%, 0.13%, and 0.06% for CO2, CH4, and N2O, respectively. This collaborative development effort also represents the first of its kind for a gaseous SRM developed by NIST. PMID- 26890891 TI - 30 Days Wild: Development and Evaluation of a Large-Scale Nature Engagement Campaign to Improve Well-Being. AB - There is a need to increase people's engagement with and connection to nature, both for human well-being and the conservation of nature itself. In order to suggest ways for people to engage with nature and create a wider social context to normalise nature engagement, The Wildlife Trusts developed a mass engagement campaign, 30 Days Wild. The campaign asked people to engage with nature every day for a month. 12,400 people signed up for 30 Days Wild via an online sign-up with an estimated 18,500 taking part overall, resulting in an estimated 300,000 engagements with nature by participants. Samples of those taking part were found to have sustained increases in happiness, health, connection to nature and pro nature behaviours. With the improvement in health being predicted by the improvement in happiness, this relationship was mediated by the change in connection to nature. PMID- 26890893 TI - The many faces of positive hepatitis B surface antigen. PMID- 26890892 TI - Early developmental gene enhancers affect subcortical volumes in the adult human brain. AB - Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890895 TI - Measuring Impatience in Intertemporal Choice. AB - In general terms, decreasing impatience means decreasing discount rates. This property has been usually referred to as hyperbolic discounting, although there are other discount functions which also exhibit decreasing discount rates. This paper focuses on the measurement of the impatience associated with a discount function with the aim of establishing a methodology to compare this characteristic for two different discount functions. In this way, first we define the patience associated with a discount function in an interval as its corresponding discount factor and consequently we deduce that the impatience at a given moment is the corresponding instantaneous discount rate. Second we compare the degree of impatience of discount functions belonging to the same or different families, by considering the cases in which the functions do or do not intersect. PMID- 26890894 TI - Sleep disturbance in chronic military-related PTSD: clinical impact and response to adjunctive risperidone in the Veterans Affairs cooperative study #504. AB - OBJECTIVE: Sleep disturbances are common among veterans with chronic military related posttraumatic stress disorder (PTSD). This article reports the results of a multicenter clinical trial that explored the clinical correlates of reported sleep impairment in these veterans and tested the impact of the second-generation antipsychotic risperidone upon these symptoms. METHOD: This article reports secondary analyses of a 24-week multicenter randomized placebo-controlled trial of adjunctive risperidone in patients with chronic military-related PTSD symptoms (n = 267, 97% male) who were symptomatic despite treatment with antidepressants and other medications. The study was conducted between February 2007 and February 2010. DSM-IV PTSD diagnoses were made by using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Nonpatient Edition. Sleep disturbances were assessed principally by using the Pittsburgh Sleep Quality Index (PSQI) (primary outcome measure). Analyses were conducted using bivariate correlations and longitudinal mixed model regressions. RESULTS: Eighty-eight percent of the patients in this study had clinically significantly impaired sleep on the PSQI. Severity of sleep disturbances correlated with PTSD symptom severity as measured by the Clinician-Administered PTSD Scale (CAPS) and reductions in multiple measures of quality of life (Veterans RAND 36-item Health Survey [SF-36 V] subscales, Boston Life Satisfaction Index). Risperidone produced small but statistically significant effects on total PSQI scores (main effect of drug: F1,228 = 4.57, P = .034; drug-by-time interaction: F2,421 = 4.32, P = .014) and severity of nightmares as assessed by the CAPS (main effect of drug: F1,248 = 4.60, P = .033). The improvements in sleep quality produced by risperidone correlated with reductions in PTSD symptom severity and improvement in the mental health subscale of the SF-36 V. CONCLUSIONS: This study highlighted the near universality and significant negative impact of severe disturbances in sleep quality in veterans with chronic military-related PTSD who were partial responders to standard pharmacotherapies. The modest improvements in sleep quality produced by adjunctive risperidone were correlated with limited reductions in PTSD severity and improvements in quality of life. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00099983. PMID- 26890896 TI - Radical Cyclisation of alpha-Halo Aluminium Acetals: A Mechanistic Study. AB - alpha-Bromo aluminium acetals are suitable substrates for Ueno-Stork-like radical cyclisations affording gamma-lactols and acid-sensitive methylene-gamma-lactols in high yields. The mechanistic study herein sets the scope and limitation of this reaction. The influence of the halide (or chalcogenide) atom X (X=Cl, Br, I, SPh, SePh) in the precursors alpha-haloesters, as well as influence of the solvent and temperature was studied. The structure of the aluminium acetal intermediates resulting from the reduction of the corresponding alpha-haloesters has been investigated by low-temperature (13) C-INEPT diffusion-ordered NMR spectroscopy (DOSY) experiments and quantum calculations, providing new insights into the structures of these thermally labile intermediates. Oxygen-bridged dimeric structures with a planar Al2 O2 ring are proposed for the least hindered aluminium acetals, while monomeric structures seem to prevail for the most hindered species. A comparison against the radical cyclisation of aluminium acetals derived from allyl and propargyl alcohols with the parent Ueno-Stork has been made at the BHandHLYP/6-311++G(d,p) level of theory, highlighting mechanistic similarities and differences. PMID- 26890897 TI - Suppression of noise in SEM images using weighted local hysteresis smoothing filter. AB - It has been proven that Hysteresis Smoothing (HS) has several advantages for Scanning Electron Microscopy (SEM) image noise reduction. HS uses hysteresis thresholding to remove noise besides preserving important details of images. Determination of optimal threshold values (cursor width) plays an effective role in improving the performance of HS based filters. Recently, a novel local technique, named Local Adaptive Hysteresis Smoothing (LAHS), has been proposed to compute an optimal cursor width. In this paper, a new method is proposed to improve the performance of LAHS in noise reduction and detail preservation. In the proposed approach which is based on weighted averaging, local statistical characteristics of the image are used in order to modify the final values of estimated pixels by LAHS method. Proposed method is applied to SEM images corrupted by different levels of noise. Noise reduction and detail preservation performance of the proposed method is compared in both objective and subjective manners with other HS based filters. Experimental results demonstrate that the proposed method is successful in improving the performance of LAHS and also it achieves better performance in noise reduction besides detail preservation of SEM images in comparison with other HS based filters. SCANNING 38:634-643, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890898 TI - Iterative image reconstruction using non-local means with total variation from insufficient projection data. AB - In this work, algebraic reconstruction technique (ART) is extended by using non local means (NLM) and total variation (TV) for reduction of artifacts that are due to insufficient projection data. TV and NLM algorithms use different image models and their application in tandem becomes a powerful denoising method that reduces erroneous variations in the image while preserving edges and details. Simulations were performed on a widely used 2D Shepp-Logan phantom to demonstrate performance of the introduced method (ART + TV) NLM and compare it to TV based ART (ART + TV) and ART. The results indicate that (ART + TV) NLM achieves better reconstructions compared to (ART + TV) and ART. PMID- 26890900 TI - A Lossless hybrid wavelet-fractal compression for welding radiographic images. AB - In this work a lossless wavelet-fractal image coder is proposed. The process starts by compressing and decompressing the original image using wavelet transformation and fractal coding algorithm. The decompressed image is removed from the original one to obtain a residual image which is coded by using Huffman algorithm. Simulation results show that with the proposed scheme, we achieve an infinite peak signal to noise ratio (PSNR) with higher compression ratio compared to typical lossless method. Moreover, the use of wavelet transform speeds up the fractal compression algorithm by reducing the size of the domain pool. The compression results of several welding radiographic images using the proposed scheme are evaluated quantitatively and compared with the results of Huffman coding algorithm. PMID- 26890899 TI - Non-destructive evaluation of teeth restored with different composite resins using synchrotron based micro-imaging. AB - BACKGROUND: Application of high resolution synchrotron micro-imaging in microdefects studies of restored dental samples. OBJECTIVE: The purpose of this study was to identify and compare the defects in restorations done by two different resin systems on teeth samples using synchrotron based micro-imaging techniques namely Phase Contrast Imaging (PCI) and micro-computed tomography (MCT). With this aim acquired image quality was also compared with routinely used RVG (Radiovisiograph). METHODS: Crowns of human teeth samples were fractured mechanically involving only enamel and dentin, without exposure of pulp chamber and were divided into two groups depending on the restorative composite materials used. Group A samples were restored using a submicron Hybrid composite material and Group B samples were restored using a Nano-Hybrid restorative composite material. Synchrotron based PCI and MCT was performed with the aim of visualization of tooth structure, composite resin and their interface. RESULTS: The quantitative and qualitative comparison of phase contrast and absorption contrast images along with MCT on the restored teeth samples shows comparatively large number of voids in Group A samples. CONCLUSIONS: Quality assessment of dental restorations using synchrotron based micro-imaging suggests Nano-Hybrid resin restorations (Group B) are better than Group A. PMID- 26890901 TI - Fusion of multi-voltage digital radiography images based on nonsubsampled contourlet transform. AB - In order to increase the single digital radiography (DR) image information of the composite component in the industry, the different DR images are captured at different voltages so as to get the structural information at different thickness region firstly. Secondly, the original DR images are decomposed by nonsubsampled contourlet transform (NSCT), and the low-frequency subbands are fused by the role of principle component analysis (PCA), and the modified central energy role is used to carry out the high-frequency directional subbands fusion. The false edges are extracted, and the values of the high-frequency subband coefficients of the false edges are set to be a small value so as to reduce the false edges in the fusion image. Finally, the output image can be obtained by inverse nonsubsampled contourlet transform. The experimental results show that the fused DR image brings more detailed information, and the structure of the component can be seen clearly, so it is useful to the fast and accurate quality judgements of the component. PMID- 26890903 TI - Synchrotron radiation (SR) diffraction enhanced imaging (DEI) of chronic glomerulonephritis (CGN) mode. AB - OBJECTIVE: The aim of this study is to investigate microstructural changes in chronic glomerulonephritis (CGN) rabbit model under diffraction enhanced imaging (DEI) technology of synchrotron radiation (SR). MATERIALS AND METHODS: The chronic glomerulonephritis (CGN) models were obtained within two months after 5 New Zealand white rabbits were treated with doxorubicin hydrochloride. Blood exams, urine tests and kidney histological studies were carried out after the 5 rabbits were humanely sacrificed by hyperanesthesia. The kidney tissues were fixed in 4% formalin for one week before DEI experiment, with another 5 normal rabbits used as the control group. The experiment was performed at Beijing Synchrotron Radiation Facility (BSRF) with a 4W1A beam line (beam energy was 14keV). On routine scanning process, the rocking curve was detected, and slope position on the curve was selected to make a 360 degrees spatial CT scan; DEI reconstruction software was used to generate a 3-dimensional image, from which the difference in grey value between the chronic glomerulonephritis (CGN) group and the control group was measured and analyzed using MATLAB and SPSS. RESULT: Without radio-contrast, DEI provided clear visibility of the microstructures including artery, vein, straight collecting ducts, papillary tubules, glomeruli in both the chronic glomerulonephritis (CGN) group and the control group, with a spatial resolution as low as 10MUm. MATLAB grey value extraction and SPSS analysis showed that cortex of CGN group (91 to 112) lost more gray value compared to the control group (121 to 141), T tests P < 0.05. Equivalant cortical ROI (data points 450*80) quantitative analysis showed that gross grey value of CGN group (ranking from 55 to 160) was smaller than the control group (ranking from 75 to 175). DEI images correlated well with pathologic images. Morphological changes in the microstructure of contstartabstractCGN kidney was revealed, due to the advantage of phase-contrast imaging (PCI) mechanism, and the diagnostic value of CGN by synchrotron radiation (SR) phase-contrast imaging (PCI) technology was evaluated. CONCLUSION: Synchrotron radiation (SR) diffraction enhanced imaging (DEI) experiment makes non-contrast CGN diagnosis possible in the rabbit model studied. With improvement of laboratory equipment and image analyzer in clinical practice, diffraction enhanced imaging (DEI) could fundamentally become a new diagnostic method for CGN. PMID- 26890902 TI - X-ray propagation-based equally sloped tomography for mouse brain. AB - BACKGROUND: The outstanding functional importance of the brain implies a strong need for brain imaging modalities. However, the current imaging approaches that target the brain in rodents remain suboptimal. OBJECTIVE AND METHODS: In this paper, X-ray propagation-based phase contrast imaging combined with equally sloped tomography (PPCI-EST) was employed to nondestructively investigate the mouse brain. RESULTS: The grey and white matters, which have extremely small differences in electron density, were clearly discriminated. The fine structures, including the corpus callosum (cc), the optic chiasma (ox) and the caudate putamen (CPu), were revealed. Compared to the filtered back projection reconstruction, the PPCI-EST significantly reduce projection number while maintaining sufficient image quality. CONCLUSIONS: It could be a potential tool for fast and low-dose phase-contrast imaging to biomedical specimens. PMID- 26890904 TI - Diagnosed chest lesion on diffusion-weighted magnetic resonance images using apparent diffusion coefficients. AB - PURPOSE: A novel diagnostic method using the standard deviation (SD) value of apparent diffusion coefficient (ADC) by diffusion-weighted (DWI) magnetic resonance imaging (MRI) is applied for differential diagnosis of primary chest cancers, metastatic tumors and benign tumors. MATERIALS AND METHODS: This retrospective study enrolled 27 patients (20 males, 7 female; age, 15-85; mean age, 68) who had thoracic mass lesions in the last three years and underwent an MRI chest examination at our institution. In total, 29 mass lesions were analyzed using SD of ADC and DWI. Lesions were divided into five groups: Primary lung cancers (N = 10); esophageal cancers (N = 5); metastatic tumors (N = 8); benign tumors (N = 3); and inflammatory lesions (N = 3). Quantitative assessment of MRI parameters of mass lesions was performed. The ADC value was acquired based on the average of the entire tumor area. The error-plot, t-test and the area under receiver operating characteristic (AUC) were applied for statistical analysis. RESULTS: The SD of ADC value (mean+/-SD) was (4.867+/-1.359)*10-4 mm2/sec in primary lung cancers, and (3.598+/-0.350)*10-4 mm2/sec in metastatic tumors. The SD of ADC values of primary lung cancers and metastatic tumors (P < 0.05) were significantly different and the AUC was 0.800 (P < 0.05). The means of SD of ADC values was 4.532+/-1.406*10-4 mm2/sec and 2.973+/-0.364*10-4 mm2/sec for malignant tumors (including primary lung cancers, esophageal cancers) and benign tumors with respectively. The mean of SD of ADC values between malignant chest tumors and benign chest tumors was shown significant difference (P < 0.01). The values of AUC was 0.967 between malignant chest tumors and benign chest tumors (P < 0.05). The ADC values for primary lung cancers, metastatic tumors and benign tumors were not significantly difference (P > 0.05). CONCLUSIONS: The mean of SD of ADC value by DWI can be used for differential diagnosis of chest lesions. PMID- 26890905 TI - Sinogram-based attenuation correction in PET/CT. AB - In a typical positron emission tomography/computed tomography (PET/CT) system, the attenuation correction is necessary for PET image reconstruction, which involves a transformation from the CT Hounsfield units (HU) to its linear attenuation coefficient (LAC) at 511 keV. This transformation is usually aided by an empirical bilinear function, followed by the forward projection of the transformed attenuation image. In this paper, we propose a direct method that calculates attenuation factors from CT projections, without using a reconstructed CT image. In this method, the human body is considered as a mixture of three distinct components: air, water and bone. Then, we estimate the proportions of these three components along each x-ray path and restore the attenuation factor at 511 keV with the known water and bone LACs. Our numerical results show that the proposed method produces as accurate estimation as the conventional HU mapping method. PMID- 26890906 TI - Cardiac CT: A system architecture study. AB - BACKGROUND: We are interested in exploring dedicated, high-performance cardiac CT systems optimized to provide the best tradeoff between system cost, image quality, and radiation dose. OBJECTIVE: We sought to identify and evaluate a broad range of CT architectures that could provide an optimal, dedicated cardiac CT solution. METHODS: We identified and evaluated thirty candidate architectures using consistent design choices. We defined specific evaluation metrics related to cost and performance. We then scored the candidates versus the defined metrics. Lastly, we applied a weighting system to combine scores for all metrics into a single overall score for each architecture. CT experts with backgrounds in cardiovascular radiology, x-ray physics, CT hardware and CT algorithms performed the scoring and weighting. RESULTS: We found nearly a twofold difference between the most and the least promising candidate architectures. Architectures employed by contemporary commercial diagnostic CT systems were among the highest-scoring candidates. We identified six architectures that show sufficient promise to merit further in-depth analysis and comparison. CONCLUSION: Our results suggest that contemporary diagnostic CT system architectures outperform most other candidates that we evaluated, but the results for a few alternatives were relatively close. We selected six representative high-scoring candidates for more detailed design and further comparative evaluation. PMID- 26890907 TI - Breast tomosynthesis using the multiple projection algorithm adapted for stationary detectors. AB - OBJECTIVE: The aim of this study is to investigate the validity of using the Multiple Projection Algorithm (MPA) for Breast Tomosynthesis (BT) using real projection images acquired with phantoms at a clinical setting. METHODS: The CIRS BR3D phantom with ranging thicknesses between 3 cm and 6 cm was used for all image quality evaluations. Five sets of measurements were acquired, each comprised of a 2D mammographic image followed by a set of 25 projections within an arc length of 50 degrees . A reconstruction algorithm based on the MPA was adapted for partial isocentric rotation using a stationary detector. For reference purposes, a Back Projection (BP) algorithm was also developed for this geometry. The performance of the algorithms was evaluated, in combination with pre-filtering of the projections, in comparative studies that involved also a comparison between tomosynthesis slices and 2D mammograms. RESULTS: Evaluation of tomosynthesis slices reconstructed with BP and MPA showed close performance for the two algorithms with no considerable differences in feature detection, size and appearance of the background tissue with the MPA running faster the overall process. Pre-filtering of the projections, led to better BT images compared to non-filtering. Increased thickness resulted in limited detection of the features of interest, especially the smaller sized ones. In these cases, the filtered BT slices allowed improved visualization due to removed superimposed tissue compared to the 2D images. The different breast-like slab arrangements in phantoms of the same thickness demonstrated a slight influence on the quality of reconstructed features. CONCLUSIONS: The MPA which had been applied previously to reconstruct tomograms from projections acquired at synchrotron facilities, is a time efficient algorithm, and is fully compliant with and can be successfully used in BT clinical systems. Compared to 2D mammography, BT shows advantage in visualizing features of small size and for increased phantom thickness or features within a dense background with superimposed structures. PMID- 26890908 TI - Geometrical force constraint method for vessel and x-ray angiogram simulation. AB - This study proposes a novel geometrical force constraint method for 3-D vasculature modeling and angiographic image simulation. For this method, space filling force, gravitational force, and topological preserving force are proposed and combined for the optimization of the topology of the vascular structure. The surface covering force and surface adhesion force are constructed to drive the growth of the vasculature on any surface. According to the combination effects of the topological and surface adhering forces, a realistic vasculature can be effectively simulated on any surface. The image projection of the generated 3-D vascular structures is simulated according to the perspective projection and energy attenuation principles of X-rays. Finally, the simulated projection vasculature is fused with a predefined angiographic mask image to generate a realistic angiogram. The proposed method is evaluated on a CT image and three generally utilized surfaces. The results fully demonstrate the effectiveness and robustness of the proposed method. PMID- 26890909 TI - Edge-oriented dual-dictionary guided enrichment (EDGE) for MRI-CT image reconstruction. AB - In this paper, we formulate the joint/simultaneous X-ray CT and MRI image reconstruction. In particular, a novel algorithm is proposed for MRI image reconstruction from highly under-sampled MRI data and CT images. It consists of two steps. First, a training dataset is generated from a series of well registered MRI and CT images on the same patients. Then, an initial MRI image of a patient can be reconstructed via edge-oriented dual-dictionary guided enrichment (EDGE) based on the training dataset and a CT image of the patient. Second, an MRI image is reconstructed using the dictionary learning (DL) algorithm from highly under-sampled k-space data and the initial MRI image. Our algorithm can establish a one-to-one correspondence between the two imaging modalities, and obtain a good initial MRI estimation. Both noise-free and noisy simulation studies were performed to evaluate and validate the proposed algorithm. The results with different under-sampling factors show that the proposed algorithm performed significantly better than those reconstructed using the DL algorithm from MRI data alone. PMID- 26890910 TI - Noncontact Capacitive Sensing-Based Locomotion Transition Recognition for Amputees With Robotic Transtibial Prostheses. AB - Recent advancement of robotic transtibial prostheses can restore human ankle dynamics in different terrains. Automatic locomotion transitions of the prosthesis guarantee the amputee's safety and smooth motion. In this paper, we present a noncontact capacitive sensing-based approach for recognizing locomotion transitions of amputees with robotic transtibial prostheses. The proposed sensing system is designed with flexible printed circuit boards which solves the walking instability brought by our previous system when using robotic prosthesis and improves the recognition performance. Six transtibial amputees were recruited and performed tasks of ten locomotion transitions with the robotic prosthesis that we recently constructed. The capacitive sensing system was integrated on the prosthesis and worked in combination with on-prosthesis mechanical sensors. With the cascaded classification method, the proposed system achieved 95.8% average recognition accuracy by support vector machine (SVM) classifier and 94.9% accuracy by quadratic discriminant analysis (QDA) classifier. It could accurately recognize the upcoming locomotion modes from the stance phase of the transition steps. In addition, we proved that adding capacitance signals could significantly reduce recognition errors of the robotic prosthesis in locomotion transition tasks. Our study suggests that the fusion of capacitive sensing system and mechanical sensors is a promising alternative for controlling the robotic transtibial prosthesis. PMID- 26890912 TI - Implementation of EMG- and Force-Based Control Interfaces in Active Elbow Supports for Men With Duchenne Muscular Dystrophy: A Feasibility Study. AB - While there is an extensive number of studies on the development and evaluation of electromyography (EMG)- and force-based control interfaces for assistive devices, no studies have focused on testing these control strategies for the specific case of adults with Duchenne muscular dystrophy (DMD). This paper presents a feasibility study on the use of EMG and force as control interfaces for the operation of active arm supports for men with DMD. We have built an experimental active elbow support, with a threefold objective: 1) to investigate whether adult men with DMD could use EMG- and force-based control interfaces; 2) to evaluate their performance during a discrete position-tracking task; and 3) to examine users' acceptance of the control methods. The system was tested in three adults with DMD (21-22 years). Although none of the three participants had performed any voluntary movements with their arms for the past 3-5 years, all of them were 100% successful in performing the series of tracking tasks using both control interfaces (mean task completion time EMG: [Formula: see text] , force: [Formula: see text] ). While movements with the force-based control were considerably smoother in Subject 3 and faster in Subject 1, EMG based-control was perceived as less fatiguing by all three subjects. Both EMG- and force-based interfaces are feasible solutions for the control of active elbow supports in adults with DMD and should be considered for further investigations on multi-DOF control. PMID- 26890913 TI - Effectiveness of High-Intensity Laser Therapy in Subacromial Impingement Syndrome. AB - OBJECTIVE: The short-term effectiveness of high-intensity laser therapy (HILT) was investigated as a retrospective case series for the treatment of the pain and disability associated with subacromial impingement syndrome (SAIS). MATERIALS AND METHODS: A total of 42 patients, who were diagnosed with subacromial impingement syndrome, underwent a total of nine sessions (three sessions per week) of high intensity laser therapy. The patients were evaluated before therapy and 8 weeks after therapy using the pain and disability subscales and the total scores of the Shoulder Pain and Disability Index (SPADI), as well as scores for the University of California at Los Angeles (UCLA) shoulder rating scale. RESULTS: Significant differences were observed between SPADI pain, disability, and total scores and UCLA scores of the patients. CONCLUSIONS: HILT was found to be effective in the short term in the treatment of pain and disability in patients with SAIS. PMID- 26890911 TI - Compensating Hand Function in Chronic Stroke Patients Through the Robotic Sixth Finger. AB - A novel solution to compensate hand grasping abilities is proposed for chronic stroke patients. The goal is to provide the patients with a wearable robotic extra-finger that can be worn on the paretic forearm by means of an elastic band. The proposed prototype, the Robotic Sixth Finger, is a modular articulated device that can adapt its structure to the grasped object shape. The extra-finger and the paretic hand act like the two parts of a gripper cooperatively holding an object. We evaluated the feasibility of the approach with four chronic stroke patients performing a qualitative test, the Frenchay Arm Test. In this proof of concept study, the use of the Robotic Sixth Finger has increased the total score of the patients by two points in a five points scale. The subjects were able to perform the two grasping tasks included in the test that were not possible without the robotic extra-finger. Adding a robotic opposing finger is a very promising approach that can significantly improve the functional compensation of the chronic stroke patient during everyday life activities. PMID- 26890914 TI - Self-Reported Medication Adherence Barriers Among Ambulatory Older Adults with Mild Cognitive Impairment. AB - STUDY OBJECTIVE: To compare the frequencies of barriers to medication adherence reported by ambulatory older adults with a diagnosis of mild cognitive impairment (MCI) and ambulatory older adults with normal cognition. DESIGN: Cross-sectional study. SETTING: Outpatient clinics within a safety-net health care system. PARTICIPANTS: Ambulatory older adults (>= 65 yrs) with a diagnosis of MCI (96 participants) or normal cognition (104 participants). MEASUREMENTS AND MAIN RESULTS: Self-reported beliefs and barriers to medication nonadherence were assessed by items from the Morisky Medication Adherence Survey, the Adherence Estimator, and barriers derived from a systematic review of studies in older adults with cognitive impairment. Participants with a diagnosis of MCI had a mean age of 72 years, 77% were female, and 37% were African-American. Participants with normal cognition had a mean age of 76 years, 79% were female, and 47% were African-American. Among all participants, 83% reported the presence of at least one barrier to medication adherence, and 62.5% reported two or more barriers to medication adherence. The most commonly reported barriers were difficulty remembering the amount or time of each medication to take (49%), difficulty opening or reading prescription bottles (42%), feeling worse when taking medications (29%), and trouble affording medications (26%). Considering the multiple comparisons made in this analysis, few significant differences in barrier frequencies were identified between the groups with MCI and normal cognition. CONCLUSION: Multiple medication adherence barriers were identified among all participants, including cognitive, physical, and financial barriers, although few significant differences were identified between those with and without MCI. Interventions capable of addressing multiple barriers are required to improve medication adherence in older adults with and without MCI. PMID- 26890915 TI - Emerging Role of Olanzapine for Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting. AB - The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) continues to pose a challenge for clinicians. The development of 5 hydroxytryptamine (serotonin) antagonists and neurokinin-1 receptor antagonists (NK1 -RAs) have demonstrated significant improvements in acute and delayed CINV for highly and moderately emetogenic chemotherapy. Delayed and breakthrough CINV, however, continue to be difficult to manage despite available treatment agents. Randomized clinical trial data suggest that olanzapine, a second-generation thienobenzodiazepine, traditionally used in the treatment of manifestations of psychotic disorders, is an effective agent in these clinical settings. The short term use of olanzapine has a favorable adverse event profile and was not associated with grade 3 or 4 toxicity in a phase III study. Olanzapine is recommended as an option within first-line prophylaxis for CINV in the National Comprehensive Cancer Network (NCCN) guidelines and is an option for treatment of refractory CINV in the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology and NCCN guidelines. PMID- 26890916 TI - Structure and cohesive energy of dipolar helices. AB - This paper deals with the investigation of cohesive energy in dipolar helices made up of hard spheres. Such tubular helical structures are ubiquitous objects in biological systems. We observe a complex dependence of cohesive energy on surface packing fraction and dipole moment distribution. As far as single helices are concerned, the lowest cohesive energy is achieved at the highest surface packing fraction. Besides, a striking non-monotonic behavior is reported for the cohesive energy as a function of the surface packing fraction. For multiple helices, we discover a new phase, exhibiting markedly higher cohesive energy. This phase is referred to as ZZ tube consisting of stacked crown rings (reminiscent of a pile of zig-zag rings), resulting in a local triangular arrangement with densely packed filaments parallel to the tube axis. PMID- 26890917 TI - The selection of children from low-income families into preschool. AB - Because children from low-income families benefit from preschool but are less likely than other children to enroll, identifying factors that promote their enrollment can support research and policy aiming to reduce socioeconomic disparities in education. In this study, we tested an accommodations model with data on 6,250 children in the Early Childhood Longitudinal Study-Birth Cohort. In general, parental necessity (e.g., maternal employment) and human capital considerations (e.g., maternal education) most consistently predicted preschool enrollment among children from low-income families. Supply side factors (e.g., local child care options) and more necessity and human capital factors (e.g., having fewer children, desiring preparation for school) selected such children into preschool over parental care or other care arrangements, and several necessity factors (e.g., being less concerned about costs) selected them into non Head Start preschools over Head Start programs. Systemic connections and child elicitation did not consistently predict preschool enrollment in this population. PMID- 26890919 TI - Packet Fragmentation and Reassembly in Molecular Communication. AB - This paper describes packet fragmentation and reassembly to achieve reliable molecular communication among bionanomachines. In the molecular communication described in this paper, a sender bionanomachine performs packet fragmentation, dividing a large molecular message into smaller pieces and embedding into smaller molecular packets, so that molecular packets have higher diffusivity to reach the receiver bionanomachine. The receiver bionanomachine then performs packet reassembly to retrieve the original molecular message from a set of molecular packets that it receives. To examine the effect of packet fragmentation and reassembly, we develop analytical models and conduct numerical experiments. Numerical results show that packet fragmentation and reassembly can improve the message delivery performance. Numerical results also indicate that packet fragmentation and reassembly may degrade the performance in the presence of drift in the environment. PMID- 26890918 TI - Attention Deficit/Hyperactivity Disorder and Urinary Nonylphenol Levels: A Case Control Study in Taiwanese Children. AB - OBJECTIVE: Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. METHODS: A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP IV) questionnaire was used to identify normal controls aged 4-15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. RESULTS: A total of 97 children with doctor diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57+/-0.73 vs. 1.73+/-0.77 MUg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52+/-3.22 MUg/g cr. vs. 4.64+/-2.95 MUg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. CONCLUSION: This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations. PMID- 26890920 TI - Prediction and Validation of Disease Genes Using HeteSim Scores. AB - Deciphering the gene disease association is an important goal in biomedical research. In this paper, we use a novel relevance measure, called HeteSim, to prioritize candidate disease genes. Two methods based on heterogeneous networks constructed using protein-protein interaction, gene-phenotype associations, and phenotype-phenotype similarity, are presented. In HeteSim_MultiPath (HSMP), HeteSim scores of different paths are combined with a constant that dampens the contributions of longer paths. In HeteSim_SVM (HSSVM), HeteSim scores are combined with a machine learning method. The 3-fold experiments show that our non machine learning method HSMP performs better than the existing non-machine learning methods, our machine learning method HSSVM obtains similar accuracy with the best existing machine learning method CATAPULT. From the analysis of the top 10 predicted genes for different diseases, we found that HSSVM avoid the disadvantage of the existing machine learning based methods, which always predict similar genes for different diseases. The data sets and Matlab code for the two methods are freely available for download at http://lab.malab.cn/data/HeteSim/index.jsp. PMID- 26890921 TI - Drug-Target Interaction Prediction with Graph Regularized Matrix Factorization. AB - Experimental determination of drug-target interactions is expensive and time consuming. Therefore, there is a continuous demand for more accurate predictions of interactions using computational techniques. Algorithms have been devised to infer novel interactions on a global scale where the input to these algorithms is a drug-target network (i.e., a bipartite graph where edges connect pairs of drugs and targets that are known to interact). However, these algorithms had difficulty predicting interactions involving new drugs or targets for which there are no known interactions (i.e., "orphan" nodes in the network). Since data usually lie on or near to low-dimensional non-linear manifolds, we propose two matrix factorization methods that use graph regularization in order to learn such manifolds. In addition, considering that many of the non-occurring edges in the network are actually unknown or missing cases, we developed a preprocessing step to enhance predictions in the "new drug" and "new target" cases by adding edges with intermediate interaction likelihood scores. In our cross validation experiments, our methods achieved better results than three other state-of-the art methods in most cases. Finally, we simulated some "new drug" and "new target" cases and found that GRMF predicted the left-out interactions reasonably well. PMID- 26890922 TI - A Modified Multiple Alignment Fast Fourier Transform with Higher Efficiency. AB - Multiple sequence alignment (MSA) is the most common task in bioinformatics. Multiple alignment fast Fourier transform (MAFFT) is the fastest MSA program among those the accuracy of the resulting alignments can be comparable with the most accurate MSA programs. In this paper, we modify the correlation computation scheme of the MAFFT for further efficiency improvement in three aspects. First, novel complex number based amino acid and nucleotide expressions are utilized in the modified correlation. Second, linear convolution with a limitation is proposed for computing the correlation of amino acid and nucleotide sequences. Third, we devise a fast Fourier transform (FFT) algorithm for computing linear convolution. The FFT algorithm is based on conjugate pair split-radix FFT and does not require the permutation of order, and it is new as only real parts of the final outputs are required. Simulation results show that the speed of the modified scheme is 107.58 to 365.74 percent faster than that of the original MAFFT for one execution of the function Falign() of MAFFT, indicating its faster realization. PMID- 26890923 TI - Efficient Constant-Time Complexity Algorithm for Stochastic Simulation of Large Reaction Networks. AB - Exact stochastic simulation is an indispensable tool for a quantitative study of biochemical reaction networks. The simulation realizes the time evolution of the model by randomly choosing a reaction to fire and update the system state according to a probability that is proportional to the reaction propensity. Two computationally expensive tasks in simulating large biochemical networks are the selection of next reaction firings and the update of reaction propensities due to state changes. We present in this work a new exact algorithm to optimize both of these simulation bottlenecks. Our algorithm employs the composition-rejection on the propensity bounds of reactions to select the next reaction firing. The selection of next reaction firings is independent of the number reactions while the update of propensities is skipped and performed only when necessary. It therefore provides a favorable scaling for the computational complexity in simulating large reaction networks. We benchmark our new algorithm with the state of the art algorithms available in literature to demonstrate its applicability and efficiency. PMID- 26890924 TI - Nephron Sparing Surgery for Renal Mass: Is There Any Difference between Oncocytoma and Malignant Lesions. AB - INTRODUCTION: A relatively high proportion of patients who undergo partial or radical nephrectomy for enhancing renal mass actually have oncocytoma, a benign renal tumor. Several parameters have been shown to be typical for oncocytoma, but only a small number of patients present with these parameters. The aim of our study was to report the clinical, operative and postoperative characteristics of patients who underwent nephron-sparing surgery in our center with a histopathological diagnosis of oncocytoma compared to patients with malignant renal tumor. PATIENTS AND METHODS: Sixty-three out of 530 patients who underwent nephron-sparing surgery for enhancing renal mass were diagnosed with oncocytoma. Clinical and radiological features and operational data of these patients were compared with patients who had malignant renal tumors. RESULTS: Mean age of patients with histologically proven non-malignant oncocytoma was significantly higher than that in patients with malignant renal cell carcinoma (66.7 vs. 61.4 years). All other analyzed variables showed no significant difference between the 2 groups. CONCLUSIONS: No reliable clinical, operative or radiological parameters can differentiate preoperatively between oncocytoma and malignant renal neoplasms. PMID- 26890925 TI - Robust Recurrent Kernel Online Learning. AB - We propose a robust recurrent kernel online learning (RRKOL) algorithm based on the celebrated real-time recurrent learning approach that exploits the kernel trick in a recurrent online training manner. The novel RRKOL algorithm guarantees weight convergence with regularized risk management through the use of adaptive recurrent hyperparameters for superior generalization performance. Based on a new concept of the structure update error with a variable parameter length, we are the first one to propose the detailed structure update error, such that the weight convergence and robust stability proof can be integrated with a kernel sparsification scheme based on a solid theoretical ground. The RRKOL algorithm automatically weighs the regularized term in the recurrent loss function, such that we not only minimize the estimation error but also improve the generalization performance through sparsification with simulation support. PMID- 26890926 TI - Mixtures of Conditional Random Fields for Improved Structured Output Prediction. AB - The conditional random field (CRF) is a successful probabilistic model for structured output prediction problems. In this brief, we consider to enlarge the representational capacity of CRF via mixture modeling. The motivation is that a single CRF can perform well if the data conform to the statistical dependence assumption imposed by the CRF model structure, whereas it may potentially fail to model the data that come from multiple different sources or domains. For the conventional conditional likelihood objective, we derive the expectation maximization algorithm in conjunction with the direct gradient ascent method for learning a CRF mixture with sequence or image-structured data. In addition, we provide alternative mixture learning algorithms that aim to maximize either the classification margin or the sitewise conditional likelihood, which were previously shown to outperform the conventional estimator for single CRF models in a variety of situations. We demonstrate the improved prediction accuracy of the proposed mixture learning algorithms on several important sequence labeling problems. PMID- 26890927 TI - Deep Direct Reinforcement Learning for Financial Signal Representation and Trading. AB - Can we train the computer to beat experienced traders for financial assert trading? In this paper, we try to address this challenge by introducing a recurrent deep neural network (NN) for real-time financial signal representation and trading. Our model is inspired by two biological-related learning concepts of deep learning (DL) and reinforcement learning (RL). In the framework, the DL part automatically senses the dynamic market condition for informative feature learning. Then, the RL module interacts with deep representations and makes trading decisions to accumulate the ultimate rewards in an unknown environment. The learning system is implemented in a complex NN that exhibits both the deep and recurrent structures. Hence, we propose a task-aware backpropagation through time method to cope with the gradient vanishing issue in deep training. The robustness of the neural system is verified on both the stock and the commodity future markets under broad testing conditions. PMID- 26890928 TI - Deep Neural Network for Structural Prediction and Lane Detection in Traffic Scene. AB - Hierarchical neural networks have been shown to be effective in learning representative image features and recognizing object classes. However, most existing networks combine the low/middle level cues for classification without accounting for any spatial structures. For applications such as understanding a scene, how the visual cues are spatially distributed in an image becomes essential for successful analysis. This paper extends the framework of deep neural networks by accounting for the structural cues in the visual signals. In particular, two kinds of neural networks have been proposed. First, we develop a multitask deep convolutional network, which simultaneously detects the presence of the target and the geometric attributes (location and orientation) of the target with respect to the region of interest. Second, a recurrent neuron layer is adopted for structured visual detection. The recurrent neurons can deal with the spatial distribution of visible cues belonging to an object whose shape or structure is difficult to explicitly define. Both the networks are demonstrated by the practical task of detecting lane boundaries in traffic scenes. The multitask convolutional neural network provides auxiliary geometric information to help the subsequent modeling of the given lane structures. The recurrent neural network automatically detects lane boundaries, including those areas containing no marks, without any explicit prior knowledge or secondary modeling. PMID- 26890929 TI - Learning Kernel Extended Dictionary for Face Recognition. AB - A sparse representation classifier (SRC) and a kernel discriminant analysis (KDA) are two successful methods for face recognition. An SRC is good at dealing with occlusion, while a KDA does well in suppressing intraclass variations. In this paper, we propose kernel extended dictionary (KED) for face recognition, which provides an efficient way for combining KDA and SRC. We first learn several kernel principal components of occlusion variations as an occlusion model, which can represent the possible occlusion variations efficiently. Then, the occlusion model is projected by KDA to get the KED, which can be computed via the same kernel trick as new testing samples. Finally, we use structured SRC for classification, which is fast as only a small number of atoms are appended to the basic dictionary, and the feature dimension is low. We also extend KED to multikernel space to fuse different types of features at kernel level. Experiments are done on several large-scale data sets, demonstrating that not only does KED get impressive results for nonoccluded samples, but it also handles the occlusion well without overfitting, even with a single gallery sample per subject. PMID- 26890930 TI - Learning Discriminative Subspaces on Random Contrasts for Image Saliency Analysis. AB - In visual saliency estimation, one of the most challenging tasks is to distinguish targets and distractors that share certain visual attributes. With the observation that such targets and distractors can sometimes be easily separated when projected to specific subspaces, we propose to estimate image saliency by learning a set of discriminative subspaces that perform the best in popping out targets and suppressing distractors. Toward this end, we first conduct principal component analysis on massive randomly selected image patches. The principal components, which correspond to the largest eigenvalues, are selected to construct candidate subspaces since they often demonstrate impressive abilities to separate targets and distractors. By projecting images onto various subspaces, we further characterize each image patch by its contrasts against randomly selected neighboring and peripheral regions. In this manner, the probable targets often have the highest responses, while the responses at background regions become very low. Based on such random contrasts, an optimization framework with pairwise binary terms is adopted to learn the saliency model that best separates salient targets and distractors by optimally integrating the cues from various subspaces. Experimental results on two public benchmarks show that the proposed approach outperforms 16 state-of-the-art methods in human fixation prediction. PMID- 26890931 TI - Ultrasonic Welding of Thermoplastic Composite Coupons for Mechanical Characterization of Welded Joints through Single Lap Shear Testing. AB - This paper presents a novel straightforward method for ultrasonic welding of thermoplastic-composite coupons in optimum processing conditions. The ultrasonic welding process described in this paper is based on three main pillars. Firstly, flat energy directors are used for preferential heat generation at the joining interface during the welding process. A flat energy director is a neat thermoplastic resin film that is placed between the parts to be joined prior to the welding process and heats up preferentially owing to its lower compressive stiffness relative to the composite substrates. Consequently, flat energy directors provide a simple solution that does not require molding of resin protrusions on the surfaces of the composite substrates, as opposed to ultrasonic welding of unreinforced plastics. Secondly, the process data provided by the ultrasonic welder is used to rapidly define the optimum welding parameters for any thermoplastic composite material combination. Thirdly, displacement control is used in the welding process to ensure consistent quality of the welded joints. According to this method, thermoplastic-composite flat coupons are individually welded in a single lap configuration. Mechanical testing of the welded coupons allows determining the apparent lap shear strength of the joints, which is one of the properties most commonly used to quantify the strength of thermoplastic composite welded joints. PMID- 26890932 TI - Homomorphic Deconvolution for MUAP Estimation From Surface EMG Signals. AB - This paper presents a technique for parametric model estimation of the motor unit action potential (MUAP) from the surface electromyography (sEMG) signal by using homomorphic deconvolution. The cepstrum-based deconvolution removes the effect of the stochastic impulse train, which originates the sEMG signal, from the power spectrum of sEMG signal itself. In this way, only information on MUAP shape and amplitude were maintained, and then, used to estimate the parameters of a time domain model of the MUAP itself. In order to validate the effectiveness of this technique, sEMG signals recorded during several biceps curl exercises have been used for MUAP amplitude and time scale estimation. The parameters so extracted as functions of time were used to evaluate muscle fatigue showing a good agreement with previously published results. PMID- 26890933 TI - Adaptive Dictionary Reconstruction for Compressed Sensing of ECG Signals. AB - This paper proposes a novel adaptive dictionary (AD) reconstruction scheme to improve the performance of compressed sensing (CS) with electrocardiogram signals (ECG). The method is based on the use of multiple dictionaries, created using dictionary learning (DL) techniques for CS signal reconstruction. The modified reconstruction framework is a two-stage process that leverages information about the signal from an initial signal reconstruction stage. By identifying whether a QRS complex is present and if so, determining a location estimate of the QRS, the most appropriate dictionary is selected and a second stage more refined signal reconstruction can be obtained. The performance of the proposed algorithm is compared with state-of-the-art CS implementations in the literature, as well as the set partitioning in hierarchical trees (SPIHT) wavelet-based lossy compression algorithm. The results indicate that the proposed reconstruction scheme outperforms all existing CS implementations in terms of signal fidelity at each compression ratio tested. The performance of the proposed approach also compares favorably with SPIHT in terms of signal reconstruction quality. Furthermore, an analysis of the overall power consumption of the proposed ECG compression framework as would be used in a body area network (BAN) demonstrates positive results for the proposed CS approach when compared with existing CS techniques and SPIHT. PMID- 26890934 TI - Interrater reliability of emergency physician-performed ultrasonography for diagnosing femoral, popliteal, and great saphenous vein thromboses compared to the criterion standard study by radiology. AB - PURPOSE: To assess the interrater reliability and test characteristics of lower limb sonographic examination for the diagnosis of deep venous and proximal great saphenous vein thrombosis when performed by Emergency Physicians (EPs) as compared to that by the Department of Radiology (Radiology). The secondary objective was to assess the effects of patient body mass index and EP satisfaction with bedside ultrasound on sensitivity and specificity. METHODS: A prospective study was conducted for patients with clinical suspicion for lower extremity thrombus. EPs evaluated for venous thrombosis in the common femoral vein, femoral vein of the thigh, popliteal vein, and proximal great saphenous vein. Subsequently, all patients received ultrasounds by Radiology, the criterion standard. RESULTS: One hundred ninety-seven patients (257 individual legs) were evaluated. There was 90-95% agreement between EP and Radiology, moderate kappa agreement for common femoral vein, and femoral vein of the thigh and fair kappa agreement for great saphenous vein and popliteal vein. The sensitivity and specificity of EP ultrasounds compared with criterion standard were lower than previously reported. There was no trend in patient body mass index or provider satisfaction influencing the test characteristics. CONCLUSIONS: Our study suggests that point-of-care sonography should not replace Radiology-performed scans. The required amount of training for EPs to be competent in this examination needs further investigation. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:360-367, 2016. PMID- 26890935 TI - The useful field of view assessment predicts simulated commercial motor vehicle driving safety. AB - OBJECTIVE: The Useful Field of View (UFOV) assessment, a measure of visual speed of processing, has been shown to be a predictive measure of motor vehicle collision (MVC) involvement in an older adult population, but it remains unknown whether UFOV predicts commercial motor vehicle (CMV) driving safety during secondary task engagement. The purpose of this study is to determine whether the UFOV assessment predicts simulated MVCs in long-haul CMV drivers. METHOD: Fifty licensed CMV drivers (Mage = 39.80, SD = 8.38, 98% male, 56% Caucasian) were administered the 3-subtest version of the UFOV assessment, where lower scores measured in milliseconds indicated better performance. CMV drivers completed 4 simulated drives, each spanning approximately a 22.50-mile distance. Four secondary tasks were presented to participants in a counterbalanced order during the drives: (a) no secondary task, (b) cell phone conversation, (c) text messaging interaction, and (d) e-mailing interaction with an on-board dispatch device. RESULTS: The selective attention subtest significantly predicted simulated MVCs regardless of secondary task. Each 20 ms slower on subtest 3 was associated with a 25% increase in the risk of an MVC in the simulated drive. The e-mail interaction secondary task significantly predicted simulated MVCs with a 4.14 times greater risk of an MVC compared to the no secondary task condition. Subtest 3, a measure of visual speed of processing, significantly predicted MVCs in the email interaction task. Each 20 ms slower on subtest 3 was associated with a 25% increase in the risk of an MVC during the email interaction task. CONCLUSIONS: The UFOV subtest 3 may be a promising measure to identify CMV drivers who may be at risk for MVCs or in need of cognitive training aimed at improving speed of processing. Subtest 3 may also identify CMV drivers who are particularly at risk when engaged in secondary tasks while driving. PMID- 26890936 TI - D-Penicillamine modulates hydrogen sulfide (H2S) pathway through selective inhibition of cystathionine-gamma-lyase. AB - BACKGROUND AND PURPOSE: Hydrogen sulfide (H2S) is a gasotransmitter produced from L-cysteine through the enzymatic action of cystathionine-gamma-lyase (CSE) and/or cystathionine-beta-synthase. D-Penicillamine is the d isomer of a dimethylated cysteine and has been used for the treatment of rheumatoid arthritis. AsD penicillamine is structurally very similar to cysteine, we have investigated whether D-penicillamine, as a cysteine analogue, has an effect on the H2 S pathway. EXPERIMENTAL APPROACH: We tested the effect of D-penicillamine (0.01-1 mM) in mouse aortic rings mounted in isolated organ baths and determined whether it could affect H2 S biosynthesis. In particular, we investigated any possible inhibitor or donor behaviour by using recombinant enzyme-based assays and an in vivo approach. KEY RESULTS: D-Penicillamine, per se, showed little or no vasodilator effect, and it cannot be metabolized as a substrate in place of l cysteine. However, d-penicillamine significantly reduced L-cysteine-induced vasodilatation in a concentration-dependent manner through inhibition of H2 S biosynthesis, and this effect occurred at concentrations 10 times lower than those needed to induce the release of H2 S. In particular, D-penicillamine selectively inhibited CSE in a pyridoxal-5'-phosphate-dependent manner. CONCLUSIONS AND IMPLICATIONS: Taken together, our results suggest that D penicillamine acts as a selective CSE inhibitor, leading to new perspectives in the design and use of specific pharmacological tools for H2 S research. In addition, the inhibitory effect of D-penicillamine on CSE could account for its beneficial action in rheumatoid arthritis patients, where H2 S has been shown to have a detrimental effect. PMID- 26890937 TI - The diagnostic accuracy of brief versions of the Geriatric Depression Scale: a systematic review and meta-analysis. AB - BACKGROUND: Depression in older adults is often under recognised despite it being the most common mental health illness in this age group. An increasing older adult population highlights the need for improved diagnostic rates. Brief versions (15 items or less) of the Geriatric Depression Scale (GDS), which are suitable for busy clinical practice, could improve detection rates. OBJECTIVE: Our aim is to establish the diagnostic accuracy of brief versions of the GDS. METHODS: Twelve electronic databases of published and unpublished literature were searched. Study selection was in accordance with predefined inclusion and exclusion criteria. A recognised gold-standard diagnostic instrument was used as a comparator against data pertaining to the use of a brief version of the GDS in an older adult population. The QUADAS-II was utilised for quality assessment. Narrative analysis and, where possible, meta-analysis were performed. RESULTS: Thirty-two studies were identified that provided diagnostic data regarding seven brief versions of the GDS (1, 4, 5, 7 8, 10 and 15-item versions). Pooled sensitivity was 0.89 (95% confidence interval (CI) 0.80-0.94), and specificity was 0.77 (95% CI 0.65-0.86) for the GDS-15 at the recommended cut-off score of 5. Meta-analysis of other brief versions was not possible because of an insufficient number of studies with standardised items. CONCLUSIONS: Results suggest the possibility of selective reporting of cut-off scores, and therefore, findings should be approached cautiously. Studies should report all cut-off scores, and all brief GDS versions should be compiled of standardised items. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890938 TI - Combination therapy with beta3 -adrenoceptor agonists and muscarinic acetylcholine receptor antagonists: Efficacy in rats with bladder overactivity. AB - OBJECTIVE: To investigate the efficacy of combination therapy of a selective beta3 -adrenoceptor agonist (mirabegron) and muscarinic acetylcholine receptor antagonists (a selective muscarinic acetylcholine receptor2 antagonist: methoctramine hemihydrate or a selective muscarinic acetylcholine receptor3 antagonist; 4-DAMP) compared with monotherapy of either agent in rats with oxotremorine methiodide (a non-selective muscarinic acetylcholine receptor agonist)-induced bladder overactivity. METHODS: Cystometry was carried out in conscious female rats with intravesical instillation of oxotremorine methiodide (200 MUmol/L). Either mirabegron (0.3-3 mg/kg), methoctramine (0.1-1 mg/kg) or 4 DAMP (0.03-0.3 mg/kg) was cumulatively applied intravenously. Also, the effects of combined application of mirabegron (3 mg/kg) plus methoctramine (1 mg/kg) or 4 DAMP (0.3 mg/kg) on cystometric parameters were compared with those of single agent monotherapy. RESULTS: Intravesical instillation of oxotremorine methiodide induced bladder overactivity, as evidenced by decreases in threshold pressure and bladder capacity. In oxotremorine methiodide-treated rats, single application of mirabegron (1, 3 mg/kg), methoctramine (0.3, 1 mg/kg) or 4-DAMP (0.1, 0.3 mg/kg) decreased baseline pressure and increased bladder capacity. In addition, reductions in threshold pressure and maximal voiding pressure were also seen after the administration of 4-DAMP (0.3 mg/kg). The combined treatment of mirabegron plus 4-DAMP induced a larger increase in bladder capacity compared with monotherapy of either drug, whereas there were no significant changes in cystometric parameters between the combination therapy of mirabegron plus methoctramine and monotherapy of either drug. CONCLUSION: These results suggest that the combination therapy of beta3 -adrenoceptor agonists plus muscarinic acetylcholine receptor3 antagonists is more effective compared with monotherapy for the treatment of bladder overactivity. In contrast, the efficacy of beta3 adrenoceptor agonists might not be increased by the addition of muscarinic acetylcholine receptor2 antagonists. PMID- 26890940 TI - Leader-Following Consensus of Nonlinear Multiagent Systems With Stochastic Sampling. AB - This paper is concerned with sampled-data leader-following consensus of a group of agents with nonlinear characteristic. A distributed consensus protocol with probabilistic sampling in two sampling periods is proposed. First, a general consensus criterion is derived for multiagent systems under a directed graph. A number of results in several special cases without transmittal delays or with the deterministic sampling are obtained. Second, a dimension-reduced condition is obtained for multiagent systems under an undirected graph. It is shown that the leader-following consensus problem with stochastic sampling can be transferred into a master-slave synchronization problem with only one master system and two slave systems. The problem solving is independent of the number of agents, which greatly facilitates its application to large-scale networked agents. Third, the network design issue is further addressed, demonstrating the positive and active roles of the network structure in reaching consensus. Finally, two examples are given to verify the theoretical results. PMID- 26890941 TI - A Benchmark Test Suite for Dynamic Evolutionary Multiobjective Optimization. AB - Growing trend of the dynamic multiobjective optimization research in the evolutionary computation community has increased the need for challenging and conceptually simple benchmark test suite to assess the optimization performance of an algorithm. This paper proposes a new dynamic multiobjective benchmark test suite which contains a number of component functions with clearly defined properties to assess the diversity maintenance and tracking ability of a dynamic multiobjective evolutionary algorithm (MOEA). Time-varying fitness landscape modality, tradeoff connectedness, and tradeoff degeneracy are considered as these properties rarely exist in the current benchmark test instances. Cross-problem comparative study is presented to analyze the sensitivity of a given algorithm to certain fitness landscape properties. To demonstrate the use of the proposed benchmark test suite, three evolutionary multiobjective algorithms, namely nondominated sorting genetic algorithm, decomposition-based MOEA, and recently proposed Kalman-filter-based prediction approach, are analyzed and compared. Besides, two problem-specific performance metrics are designed to assess the convergence and diversity performances, respectively. By applying the proposed test suite and performance metrics, microscopic performance details of these algorithms are uncovered to provide insightful guidance to the algorithm designer. PMID- 26890943 TI - An Overview and Empirical Comparison of Distance Metric Learning Methods. AB - In this paper, we first offer an overview of advances in the field of distance metric learning. Then, we empirically compare selected methods using a common experimental protocol. The number of distance metric learning algorithms proposed keeps growing due to their effectiveness and wide application. However, existing surveys are either outdated or they focus only on a few methods. As a result, there is an increasing need to summarize the obtained knowledge in a concise, yet informative manner. Moreover, existing surveys do not conduct comprehensive experimental comparisons. On the other hand, individual distance metric learning papers compare the performance of the proposed approach with only a few related methods and under different settings. This highlights the need for an experimental evaluation using a common and challenging protocol. To this end, we conduct face verification experiments, as this task poses significant challenges due to varying conditions during data acquisition. In addition, face verification is a natural application for distance metric learning because the encountered challenge is to define a distance function that: 1) accurately expresses the notion of similarity for verification; 2) is robust to noisy data; 3) generalizes well to unseen subjects; and 4) scales well with the dimensionality and number of training samples. In particular, we utilize well-tested features to assess the performance of selected methods following the experimental protocol of the state of-the-art database labeled faces in the wild. A summary of the results is presented along with a discussion of the insights obtained and lessons learned by employing the corresponding algorithms. PMID- 26890942 TI - Classifying a Person's Degree of Accessibility From Natural Body Language During Social Human-Robot Interactions. AB - For social robots to be successfully integrated and accepted within society, they need to be able to interpret human social cues that are displayed through natural modes of communication. In particular, a key challenge in the design of social robots is developing the robot's ability to recognize a person's affective states (emotions, moods, and attitudes) in order to respond appropriately during social human-robot interactions (HRIs). In this paper, we present and discuss social HRI experiments we have conducted to investigate the development of an accessibility aware social robot able to autonomously determine a person's degree of accessibility (rapport, openness) toward the robot based on the person's natural static body language. In particular, we present two one-on-one HRI experiments to: 1) determine the performance of our automated system in being able to recognize and classify a person's accessibility levels and 2) investigate how people interact with an accessibility-aware robot which determines its own behaviors based on a person's speech and accessibility levels. PMID- 26890944 TI - Stochastic Set-Based Particle Swarm Optimization Based on Local Exploration for Solving the Carpool Service Problem. AB - The growing ubiquity of vehicles has led to increased concerns about environmental issues. These concerns can be mitigated by implementing an effective carpool service. In an intelligent carpool system, an automated service process assists carpool participants in determining routes and matches. It is a discrete optimization problem that involves a system-wide condition as well as participants' expectations. In this paper, we solve the carpool service problem (CSP) to provide satisfactory ride matches. To this end, we developed a particle swarm carpool algorithm based on stochastic set-based particle swarm optimization (PSO). Our method introduces stochastic coding to augment traditional particles, and uses three terminologies to represent a particle: 1) particle position; 2) particle view; and 3) particle velocity. In this way, the set-based PSO (S-PSO) can be realized by local exploration. In the simulation and experiments, two kind of discrete PSOs-S-PSO and binary PSO (BPSO)-and a genetic algorithm (GA) are compared and examined using tested benchmarks that simulate a real-world metropolis. We observed that the S-PSO outperformed the BPSO and the GA thoroughly. Moreover, our method yielded the best result in a statistical test and successfully obtained numerical results for meeting the optimization objectives of the CSP. PMID- 26890939 TI - Rab6 Is Required for Multiple Apical Transport Pathways but Not the Basolateral Transport Pathway in Drosophila Photoreceptors. AB - Polarized membrane trafficking is essential for the construction and maintenance of multiple plasma membrane domains of cells. Highly polarized Drosophila photoreceptors are an excellent model for studying polarized transport. A single cross-section of Drosophila retina contains many photoreceptors with 3 clearly differentiated plasma membrane domains: a rhabdomere, stalk, and basolateral membrane. Genome-wide high-throughput ethyl methanesulfonate screening followed by precise immunohistochemical analysis identified a mutant with a rare phenotype characterized by a loss of 2 apical transport pathways with normal basolateral transport. Rapid gene identification using whole-genome resequencing and single nucleotide polymorphism mapping identified a nonsense mutation of Rab6 responsible for the apical-specific transport deficiency. Detailed analysis of the trafficking of a major rhabdomere protein Rh1 using blue light-induced chromophore supply identified Rab6 as essential for Rh1 to exit the Golgi units. Rab6 is mostly distributed from the trans-Golgi network to a Golgi-associated Rab11-positive compartment that likely recycles endosomes or transport vesicles going to recycling endosomes. Furthermore, the Rab6 effector, Rich, is required for Rab6 recruitment in the trans-Golgi network. Moreover, a Rich null mutation phenocopies the Rab6 null mutant, indicating that Rich functions as a guanine nucleotide exchange factor for Rab6. The results collectively indicate that Rab6 and Rich are essential for the trans-Golgi network-recycling endosome transport of cargoes destined for 2 apical domains. However, basolateral cargos are sorted and exported from the trans-Golgi network in a Rab6-independent manner. PMID- 26890946 TI - Improved Stability Condition for Takagi-Sugeno Fuzzy Systems With Time-Varying Delay. AB - In this paper, the stability analysis problem of Takagi-Sugeno fuzzy systems with time-varying delay is investigated. By utilizing the Wirtinger-based integral inequality and the improved reciprocally convex combination technique, an improved stability condition is derived in terms of linear matrix inequalities. A numerical example is given to demonstrate the efficiency of the obtained result. PMID- 26890947 TI - Robust Filtering for a Class of Networked Nonlinear Systems With Switching Communication Channels. AB - This paper is concerned with the problem of robust filter design for a class of discrete-time networked nonlinear systems. The Takagi-Sugeno fuzzy model is employed to represent the underlying nonlinear dynamics. A multi-channel communication scheme that involves a channel switching phenomenon described by a Markov chain is proposed for data transmission. Two typical communication imperfections, network-induced time-varying delays and packet dropouts are considered in each channel. The objective of this paper is to design an admissible filter such that the filter error system is stochastically stable and ensures a prescribed disturbance attenuation level bound. Based on the Lyapunov Krasovskii functional method and matrix inequality techniques, sufficient conditions on the existence of the desired filter are obtained. A numerical example is provided to illustrate the effectiveness of the proposed design approach. PMID- 26890949 TI - Movement Along the Spine Induced by Transcranial Electrical Stimulation Related Electrode Positioning. AB - STUDY DESIGN: A prospective, nonrandomized cohort study. OBJECTIVE: To describe a technique quantifying movement induced by transcranial electrical stimulation (TES) induced movement in relation to the positioning of electrodes during spinal deformity surgery. SUMMARY OF BACKGROUND DATA: TES induced movement may cause injuries and delay surgical procedures. When TES movements are evoked, muscles other than those being monitored any adjustments in stimulation protocols and electrode positioning may be expected to minimize movement whereas preserving quality of monitoring. In this study, seismic evoked responses (SER) induced through TES were studied at different electrode positions. METHODS: Intraoperative TES-motor evoked potentials were carried out in 12 patients undergoing corrective spine surgery. Accelerometer transducers recorded SER in two directions at four different locations of the spine for TES-electrode montage groups Cz-Fz and C3-C4. A paired t test was used to compare the means of SER and the relationship between movement and TES electrode positioning. RESULTS: SERs were strongest in the upper body. All mean SERs values for the Cz-Fz group were up to five times larger when compared with the C3-C4 group. However, there were no differences between the C3-C4 and Cz-Fz groups in the lower body locations. Both electrode montage groups showed a gradual stepwise reduction in all mean SER values along the spine from the cranial to caudal region. For the upper body locations, there were no significant associations between SER and both montages; in contrast, a significant association SER was demonstrated in the lumbar region. CONCLUSION: At supramaximum levels, movements resulting from multipulse TES are likely caused by relatively strong contractions from muscles in the neck resulting from direct extracranial stimulation. When interchanging electrode montages in individual cases, the movement in the neck may become reduced. At lumbar levels transcranial evoked muscle contractions dominate movement in the surgically exposed areas. LEVEL OF EVIDENCE: 4. PMID- 26890948 TI - Postoperative administration of dienogest for suppressing recurrence of disease and relieving pain in subjects with ovarian endometriomas. AB - To assess the effect of dienogest on recurrence of ovarian endometriomas and severity of pain after laparoscopic surgery, a retrospective study of 81 patients was performed at three institutions in Osaka, Japan. Patients had a six-month minimum follow-up after laparoscopic surgery for ovarian endometriomas performed between June 2012 and August 2014. Patients who chose to receive 2 mg dienogest daily and those who were managed expectantly postoperatively were included. Recurrence was defined as the presence of endometriomas of more than 2 cm. A visual analog scale (VAS) was used to score the intensity of pelvic pain. The cumulative recurrence rate and absolute VAS score changes between the baseline and at 6, 12, 18 and 24 months after the start of administration were evaluated in both groups. The recurrence rate was 16.5% and 24.0% in the expectant management group at 12 and 24 months, respectively. No recurrences occurred in the dienogest treatment group. The rate of VAS score reduction was significantly higher in the dienogest than in the expectant management group. Dienogest is effective on the recurrence of ovarian endometrioma and relieving pelvic pain after laparoscopic surgery. PMID- 26890950 TI - A Method to Prevent Occipitocervical Joint Violation Using Plain Radiography During Percutaneous Anterior Transarticular Screw Fixation. AB - STUDY DESIGN: A prospective study of anterior transarticular screw (ATS) fixation patients. OBJECTIVE: To develop a method to determine screw tip position through plain radiography after percutaneous ATS fixation to prevent occipitocervical joint (OCJ) violation. SUMMARY OF BACKGROUND DATA: No studies using plain radiography to prevent OCJ violation during percutaneous ATS fixation have been performed. METHODS: In total, 34 subjects (with 68 screws) who had undergone percutaneous ATS fixation were enrolled. To evaluate the screw tip location in relation to the C1 lateral mass (LM), the screw tip positions were graded 1, 2, or 3 on anteroposterior (AP) radiographs, and I, II, or III on lateral radiographs. OCJ violation was analyzed by postoperative computed tomography (CT). RESULTS: Screws with tips located lower (tip I) in the LM did not result in OCJ violation. Only one tip in the tip 3 position showed OCJ perforation, and this screw was also located in tip III. Screw perforation rates of tip 1-tip II, tip 1-tip III, and tip 2-tip III were the highest (100%), followed by tip 2-tip II (10.5%) and tip3-tip III (10%). CONCLUSION: This study provides insights into OCJ violation during percutaneous ATS fixation. According to AP radiography, a percutaneous ATS with the screw tip located in the lateral part of the LM resulted in a lower rate of OCJ perforation, whereas screws located in the medial LM resulted in the highest rate of perforation. Percutaneous ATS with the screw tip located in the neutral part of the LM should ensure that the screw tip is below the upper part of the LM, preventing OCJ violation. These findings may help surgeons assess screw positioning both during and after the operation. LEVEL OF EVIDENCE: 3. PMID- 26890951 TI - Lumbar Spondylolisthesis Progression and De Novo Spondylolisthesis in Elderly Chinese Men and Women: A Year-4 Follow-up Study. AB - STUDY DESIGN: Longitudinal follow-up study. OBJECTIVE: This current study aimed to further assess progression, incidence, and risk factors of lumbar spondylolisthesis in these subjects at 4-year follow-up. SUMMARY OF BACKGROUND DATA: A survey for osteoporotic fractures in Hong Kong during 2001 to 2003 represented the first large scale prospective population-based study on bone health in elderly (>=65 years) Chinese men and women. A follow-up study was performed at year-4. METHODS: The lateral lumbar radiographs of 1519 male and 1546 female subjects at year-4 follow-up were analyzed using the Meyerding classification, and compared with the baseline findings. RESULTS: Spondylolisthesis progressed in 13.0%, and de novo spondylolisthesis appeared in 12.4% in men. Spondylolisthesis progressed in 16.5%, and de novo spondylolisthesis appeared in 12.7% in women. In women, higher weight, body mass index, spine and hip bone mineral density (BMD), lower physical activity and lower grip strength were significant factors associated with spondylolisthesis progression, whereas only higher spine BMD was a marginally significant factor associated with spondylolisthesis progression for men. A weak association was noted between spondylolisthesis and lower back pain incidence in women, but not in men. CONCLUSION: Lumbar spondylolisthesis progression in elderly Chinese at 4 year follow-up was characterized by this study. LEVEL OF EVIDENCE: 3. PMID- 26890952 TI - Comparison of Cervical Kinematics, Pain, and Functional Disability Between Single and Two-level Anterior Cervical Discectomy and Fusion. AB - STUDY DESIGN: A prospective, time series design. OBJECTIVE: The purpose of this study is two-fold: firstly, to investigate the impact of altered cervical alignment and range of motion (ROM) on patients' self-reported outcomes after anterior cervical discectomy and fusion (ACDF), and secondly, to comparatively differentiate the influence of single- and two-level ACDF on the cervical ROM and adjacent segmental kinematics up to 12-month postoperatively. SUMMARY OF BACKGROUND DATA: ACDF is one of the most commonly employed surgical interventions to treat degenerative disc disease. However, there are limited in vivo data on the impact of ACDF on the cervical kinematics and its association with patient reported clinical outcomes. METHODS: Sixty-two patients (36 males; 55.63 +/- 11.6 yrs) undergoing either a single- or consecutive two-level ACDF were recruited. The clinical outcomes were assessed with the Pain Visual Analogue Scale (VAS) and the Neck Disability Index (NDI). Radiological results included cervical lordosis, global C2-C7 ROM, ROM of the Functional Spinal Unit (FSU), and its adjacent segments. The outcome measures were collected preoperatively and then at 3, 6, and 12-month postoperatively. RESULTS: A significant reduction of both VAS and NDI was found for both groups from the preoperative to 3-month period (P < 0.01). Pearson correlation revealed no significant correlation between global ROM with neither VAS (P = 0.667) nor NDI (P = 0.531). A significant reduction of global ROM was identified for the two-level ACDF group at 12 months (P = 0.017) but not for the single-level group. A significant interaction effect was identified for the upper adjacent segment ROM (P = 0.024) but not at the lower adjacent segment. CONCLUSION: Current study utilized dynamic radiographs to comparatively evaluate the biomechanical impact of single- and two-level ACDF. The results highlighted that the two-level group demonstrated a greater reduction of global ROM coupled with an increased upper adjacent segmental compensatory motions that is independent of patient-perceived recovery. LEVEL OF EVIDENCE: 3. PMID- 26890953 TI - How Effective is Physical Therapy for Common Low Back Pain Diagnoses?: A Multivariate Analysis of 4597 Patients. AB - STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study is to evaluate whether the treatment of low back pain with physical therapy results in clinically significant improvements in patient-reported pain and functional outcomes. SUMMARY OF BACKGROUND DATA: Low back pain is a major cause of morbidity and disability in health care. Previous studies have found poor efficacy for surgery in the absence of specific indications. A variety of nonoperative treatments are available; however, there is scant evidence to guide the practitioner as to the efficacy of these treatments. METHODS: Four thousand five hundred ninety-seven patients who underwent physical therapy for the nonoperative treatment of low back pain were included. The primary outcome measures were pre and post-treatment scores on the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) during activity, and NPRS during rest. Previously published thresholds for minimal clinically important difference (MCID) were used to determine the proportion of patients meeting MCID for each of our outcomes. Patients with starting values below the MCID for each variable were excluded from analysis. Logistic regression analysis was used to determine patient risk factors predictive of treatment failure. RESULTS: About 28.5% of patients met the MCID for improvement in ODI. Presence of night symptoms, obesity, and smoking were predictors of treatment failure for ODI. Fifty-nine percent of patients met the MCID for improvement in resting NPRS, with a history of venous thromboembolism, night symptoms, psychiatric disease, workers' compensation status, smoking, and obesity predictive of treatment failure. Sixty percent of patients met the MCID for improvement in activity NPRS, with night symptoms, workers' compensation status, and smoking predictive of treatment failure. CONCLUSION: We observed that a substantial percentage of the population did not meet MCID for pain and function following treatment of low back pain with physical therapy. Common risk factors for treatment failure included smoking and presence of night symptoms. LEVEL OF EVIDENCE: 4. PMID- 26890954 TI - Three-dimensional Cervical Movement Characteristics in Healthy Subjects and Subgroups of Chronic Neck Pain Patients Based on Their Pain Location. AB - STUDY DESIGN: A cross-sectional observational study of three-dimensional (3D) cervical kinematics in 41 chronic neck pain (CNPs) patients and 156 asymptomatic controls. OBJECTIVE: The objective was to investigate 3D cervical kinematics by analyzing and comparing quantitative and qualitative parameters in healthy subjects and CNPs. Furthermore, subgroups were formed to explore the influence of pain-location on cervical kinematics. The possible correlation of kinematic parameters with the degree of functional disability was examined as well. SUMMARY OF BACKGROUND DATA: In patients with chronic neck pain, a clear pathological cause is frequently not identifiable. Therefore, the need to assess neck pain with a broader view than structure or anatomical-based divergences is desirable. METHODS: Movements of the cervical spine were registered using an electromagnetic tracking system. Quantitative and qualitative kinematics were analyzed for active axial rotation, lateral bending, and flexion-extension motion components. RESULTS: During lateral bending, the range of the main motion demonstrated significant higher values (P = 0.001) in the controls (mean: 68.67 degrees +/- 15.17 degrees ) than patients (mean: 59.28 degrees +/- 15.41 degrees ). Significant differences were demonstrated between subgroups for several kinematic parameters (P < 0.05). Although differences were predominantly recorded between the "symmetrical" and "asymmetrical" pain group, some parameters also distinguished subgroups from controls. On average, the symmetrical group showed significant less harmonic movement patterns, expressed by qualitative parameters, in comparison with the "asymmetrical" group and controls. Furthermore, the "asymmetrical" group showed significant lower scores on quantitative parameters than the "symmetrical" group and controls. The degree of functional disability correlated moderately with changes in qualitative parameters. CONCLUSION: In this study, chronic neck pain patients with a symmetrical pain pattern showed significant poorer quality of movement, while those with asymmetrical pain showed a significant reduction in quantitative measures. Subgrouping of neck patients based on pain location may be of help for further research and clinics. LEVEL OF EVIDENCE: 4. PMID- 26890955 TI - Lymphocyte Count at 4 Days Postoperatively and CRP Level at 7 Days Postoperatively: Reliable and Useful Markers for Surgical Site Infection Following Instrumented Spinal Fusion. AB - STUDY DESIGN: A case-control study. OBJECTIVE: The objective of this study is to identify biochemical markers for surgical site infection (SSI) in posterior instrumented spinal fusion that are not affected by operative circumstances and to determine diagnostic cutoffs for these markers. SUMMARY OF BACKGROUND DATA: Numerous biochemical markers may be used for early detection of SSI; however, these markers may be affected by operative factors. METHODS: We reviewed data on C-reactive protein level and total white blood cell count and differential count before instrumented spinal fusion and at 1, 4, and 7 days postoperatively. The 141 patients in our sample were divided into an SSI group (patients who developed deep SSI) and a no-SSI group. We determined which markers differed significantly between groups and identified those not affected by operative circumstances (operating time, intraoperative blood loss, number of fusion segments) in the no SSI group. Then, we determined diagnostic cutoffs for these unaffected markers by using receiver-operating characteristic curves. RESULTS: Three markers were selected: lymphocyte count at 4 days postoperatively (cutoff 1180/MUL, sensitivity 90.9%, specificity 65.4%, area under the curve [AUC] 0.80), lymphocyte count of at 7 days postoperatively (cutoff <1090/MUL, sensitivity 63.6%, specificity 78.5%, AUC 0.77), and C-reactive protein level at 7 days postoperatively (cutoff >4.4 mg/dL, sensitivity 90.9%, specificity 89.2%, AUC 0.95). CONCLUSION: Lymphocyte count at 4 and 7 days postoperatively and C reactive protein level at 7 days postoperatively are reliable markers for SSI following instrumented spinal fusion. Lymphocyte count at 4 days should be useful for screening because of its high sensitivity and because it can be measured early. C-reactive protein level at 7 days should be useful for definitive diagnosis given its high sensitivity and specificity and large AUC. LEVEL OF EVIDENCE: 4. PMID- 26890956 TI - Drain Tip Culture is Not Prognostic for Surgical Site Infection in Spinal Surgery Under Prophylactic Use of Antibiotics. AB - STUDY DESIGN: A retrospective observational study. OBJECTIVE: We evaluated the prognostic value of drain tip culture performed for surgical site infection (SSI) after spinal surgery with a large number of subjects, and investigated whether the type of surgery or timing of drain removal correlated with positive drain culture and SSI rates. SUMMARY OF BACKGROUND DATA: In many institutions, routine culture of suction drain tips that are placed in the surgical site of spinal surgeries has been performed to detect contamination after removal. However, few reports have evaluated whether drain tip culture is prognostic for SSI after spinal surgery. METHODS: A total of 1240 suction drain tips that had been used in spinal surgeries were cultured after removal. Prophylactic antibiotics were administered during and after the surgery for 48 hours. We evaluated the correlation between the results of positive drain tip culture, SSI, and drain removal timing. RESULTS: Positive drain tip cultures were found in 55 cases (4.4%). True SSI was identified in 18 cases (1.5%). The most frequently isolated microorganism in the both cases was Staphylococcus. The sensitivity of drain tip culture for SSI after spinal surgery was calculated as 0% according to the concordance rate between bacteria isolated in drain tip culture and SSI cases. There was no correlation between the duration of suction drainage and the drain tip culture results or the onset of SSI within 72 hours. The results of suction drain tip culture could not reflect those of SSI regardless of the type of surgery (primary or revision), surgical region, surgical procedure, or implant use. CONCLUSION: Drain tip culture in spinal surgery was not prognostic for SSI or helpful in detecting pathogenic bacteria for SSI. Routine use of drain tip culture when prophylactic antibiotics are used is not supported by the results of this study. LEVEL OF EVIDENCE: 4. PMID- 26890957 TI - A Uniquely Shaped Rod Improves Curve Correction in Surgical Treatment of Adolescent Idiopathic Scoliosis. AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study is to determine the initial curve correction in patients surgically treated for adolescent idiopathic scoliosis (AIS) using either beam-like rods (BRs) or traditional circular rods (CRs). SUMMARY OF BACKGROUND DATA: Posterior fusion using all pedicle screw instrumentation has become the standard for the surgical treatment of AIS. Traditionally, the rod is circular in the cross-sectional plane. Recent biomechanical studies suggest that a beam-like structure of the rod may enhance the stiffness of the construct and thereby possibly improve curve correction. METHODS: Two consecutive series of patients surgically treated for AIS between May 2011 and May 2015 were included in the study. Patients were all treated with an ultralow profile all-pedicle screw implant system. In the first series, conventional 5.5 mm CoCr CR were used, and in the second series, 5.5 mm CoCr BR were used. Antero-posterior and lateral radiographs preoperatively and within seven days after surgery were used to measure the correction obtained. RESULTS: The first 60 patients were operated with CR and the subsequent 69 with BR. There was no statistical difference in age, gender, preoperative curve magnitude, Lenke type, or number of levels instrumented (P = 0.451). Major curve correction was significantly better in the BR group than in the CR group (66 vs. 57%) (P < 0.001). We found no difference in preoperative flexibility, secondary curve correction, sagittal balance, or coronal balance (P > 0.058). A postoperative decrease in thoracic kyphosis was seen with no significant difference between groups. Median T5-T12 change was -7 degrees versus -3 degrees for BR and CR, respectively (P = 0.051). CONCLUSION: A BR design results in a significantly better curve correction than conventional rods, but the difference is moderate and the clinical value is uncertain. LEVEL OF EVIDENCE: 3. PMID- 26890958 TI - Surgical Outcomes and Prognostic Factors in Patients With Diffuse Large B-cell Lymphoma-associated Metastatic Spinal Cord Compression. AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to discuss the factors that may affect surgical outcomes of patient with diffuse large B-cell lymphoma (DLBCL)-associated metastatic spinal cord compression (MSCC). SUMMARY OF BACKGROUND DATA: DLBCL in the spine is rare and minimal information has been published in the literature regarding this subject. Although DLBCL is highly sensitive to both chemotherapy and radiotherapy, surgical decompression is recommended in the treatment of DLBCL-associated MSCC. However, the prognostic factors affecting surgical outcomes of patients with DLBCL associated MSCC remain unknown. METHODS: We conducted a retrospective study to investigate the impact of surgical decompression on recovery from neurological deficit caused by DLBCL-associated MSCC. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival of spinal DLBCL. The survival rate was estimated by the Kaplan-Meier method, and differences were analyzed by the log-rank test. Factors with P values of 0.1 or less were subjected to multivariate analysis for survival rate by multivariate Cox proportional hazards analysis. RESULTS: A total of 37 patients with spinal DLBCL from 2003 to 2014 were included in the study. International Prognostic Index (IPI) (0-1/2-5), duration of preoperative symptoms (<=2m/>2m), and lactate dehydrogenase (normal/abnormal) were suggested as the potential prognostic factors through univariate analysis. However, as they were submitted to the multivariate Cox regression model, only IPI and duration of preoperative symptoms were found as independent prognostic factors. CONCLUSION: Surgical decompression improves recovery from neurological deficit. Patient IPI score plays an important role in decision making for surgical intervention, as it affects the length of survival and functional outcome. Patients with duration of preoperative symptoms no more than 2 months confer a very poor prognosis. LEVEL OF EVIDENCE: 4. PMID- 26890959 TI - Delayed Magnetic Resonance Imaging in Patients With Cervical Spinal Cord Injury Without Radiographic Abnormality. AB - STUDY DESIGN: A prospective imaging study to develop diagnostic criteria. OBJECTIVE: The aim of this study was to investigate image findings on delayed magnetic resonance imaging (MRI) after the acute phase of spinal cord injury without radiographic abnormality (SCIWORA) and their relationship with symptom severity. SUMMARY OF BACKGROUND DATA: MRI is used to diagnose acute neurological injury, with increased signal intensity (ISI) and prevertebral hyperintensity (PVH) often seen in patients with SCIWORA; however, changes after the acute phase are unclear. METHODS: We included 68 patients diagnosed with SCIWORA within 48 hours of injury. We then compared their acute (within 2 days) and delayed (after 2 weeks) MRI images. ISI grade (0-3) and ISI and PVH ranges (relative to the C3 vertebral height) were measured. Neurological status at admission and 2 weeks after injury was assessed by the Japanese Orthopaedic Association scoring system for cervical myelopathy (JOA score) and the American Spinal Injury Association impairment scale. RESULTS: For acute MRI, the rates of grade 0, 1, and 2 ISI were 4, 54, and 10 patients, respectively. For delayed MRI, the rates of grade 0, 1, and 2 ISI changed to 3, 31, and 34 patients, respectively. ISI ranges reduced in delayed MRI, but there was no significance. PVH ranges were 3.0 +/- 1.7 in acute MRI, and reduced to 1.3 +/- 0.9 with significant difference (P < 0.001). There were significant negative correlations with the JOA score for ISI grades on delayed MRI only (r = -0.49). However, there were significant negative correlations with the JOA score for the PVH range on both the acute (r = -0.55) and delayed (r = -0.46) MRI. CONCLUSION: When comparing acute and delayed MRI, there were significant differences in ISI and PVH findings. Delayed MRI also reflected the clinical symptom severity, giving useful information about the state of the spinal cord. LEVEL OF EVIDENCE: 3. PMID- 26890960 TI - Synthesis and properties of new mononuclear Ru(II)-based photocatalysts containing 4,4'-diphenyl-2,2'-bipyridyl ligands. AB - The synthesis and characterisation of a series of eleven new 4,4'-diphenyl-2,2' bipyridyl derivatives (N^N) with varying 4- or 3,5-substituents on the phenyl rings are reported. The molecular structures of two of these compounds, 4,4' bis(3,5-diheptyloxyphenyl)-2,2'-bipyridyl and 4,4'-bis(3,5-di-4,4,5,5,5 pentafluoropentyloxyphenyl)-2,2'-bipyridyl are confirmed by X-ray crystallography. Fourteen neutral complexes trans-Ru(II)Cl2(N^N)(CO)2 are prepared by reacting the new proligands and three known ones with the polymeric precursor [Ru(II)Cl2(CO)2]n, and their optical and electrochemical properties are studied. Density functional theory (DFT) and time-dependent DFT calculations have been carried out on selected complexes in order to rationalise their electronic structures and absorption properties. The low energy electronic absorption bands have metal-to-ligand charge-transfer and ligand-to-ligand charge-transfer (LLCT) character, but these dominate only in the 4-substituted species. In the 3,5 disubstituted ones, intraligand charge-transfer (ILCT) within the bpy ligands becomes more important. The complexes show only irreversible reductive electrochemistry and no signs of polymerisation. The photocatalytic oxidation behaviour of selected trans-Ru(II)Cl2(N^N)(CO)2 complexes and their mono-aquo derivatives [Ru(II)(H2O)(CO)2Cl(N^N)](+) with 4-methoxybenzyl alcohol is studied. Turnover numbers of up to ca. 130 are achieved when using [Ru(II)(bpy)3](2+) (bpy = 2,2'-bipyridyl) as photosensitizer and [Co(III)(NH3)5Cl](2+) as a sacrificial oxidant. PMID- 26890961 TI - The impact of solvents on the singlet and triplet states of selected fluorine corroles - absorption, fluorescence, and optoacoustic studies. AB - This paper examines the influence of aprotic solvents on the spectroscopic properties as well as the energy deactivation of two free-base corrole dyes substituted with C6F5 and/or 4-NO2C6H4 groups. Absorption, fluorescence and laser induced optoacoustic spectroscopy have been used to follow the singlet and triplet states of fluorine corroles belonging to the A2B and A3 type in toluene (TL), chloroform (CL), dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and also in solvent mixtures. Changes in the absorption and fluorescence spectra are influenced by the type of solvent mixture. The fluorescence behaviors of the two investigated corroles were extremely different - fluorescence of the nitro corrole in TL is dramatically quenched in the presence of DMF. In contrast, fluorescence quenching of fluorine corroles in DMF-TL mixtures is substantially weakened. Absorption, fluorescence, triplet population as well as singlet oxygen generation parameters are evaluated. The spectral experimental data are supported by quantum chemical calculations - time-dependent density functional theory (TD DFT) and cyclic voltammetry experiments. The presented results are discussed from a viewpoint of aggregation, tautomerization, and deprotonation effects occurring in the corroles. PMID- 26890963 TI - Metal-semiconductor pair nanoparticles by a physical route based on bipolar mixing. AB - In this report a methodology is described and demonstrated for preparing Au-Ge pair nanoparticles with known compositions by extending and modifying the basic steps normally used to synthesize nanoparticles in carrier gas. For the formation of pair nanoparticles by bipolar mixing, two oppositely charged aerosols of nanoparticles having the desired size are produced with the help of two differential mobility analyzers. Then both are allowed to pass through a tube, which provides sufficient residence time to result in nanoparticle pair formation due to Brownian collisions influenced by Coulomb forces. The effect of residence time on the formation of nanoparticle pairs as well as the influence of diffusion and discharging is described. Subsequently, necessary modifications to the experimental setup are demonstrated systematically. The kinetics of nanoparticles pair formation in a carrier gas is also calculated and compared with measurements made with the help of an online aerosol size analysis technique. This synthesis of nanoparticle pairs can be seen as a possible route towards Janus-type nanoparticles. PMID- 26890962 TI - Kid depletion in mouse oocytes associated with multinucleated blastomere formation and inferior embryo development. AB - This study investigated the knockdown (KD) of Kid on maturation developmental competence and multinucleation of mouse germinal vesicle (GV) oocytes after parthenogenetic activation. Data revealed that Kid messenger RNA (mRNA) was expressed in GV and MII stage oocyte and 1- and 2-cell embryos. Additionally, Kid mRNA expression in the Kid KD group decreased by nearly 46% compared to the control small interfering RNA (siRNA) groups. The rate of multinucleated embryos in the Kid KD group (52.4%) was significantly higher (P < 0.05) than the control siRNA group (4.7%). Finally, the developmental rates were significantly lower in the Kid siRNA group at > 4-cell stage (28.6% vs. 53.5%) and the blastocyst stage (2.4% vs. 23.3%) compared to the control siRNA groups. Suppression of Kid using siRNA caused multinucleation in early embryos with high frequency and it may increase 2- to 4-cell arrested embryos and reduce the developmental competence to blastocyst. PMID- 26890964 TI - Quantitative characterization of conformational-specific protein-DNA binding using a dual-spectral interferometric imaging biosensor. AB - DNA-binding proteins play crucial roles in the maintenance and functions of the genome and yet, their specific binding mechanisms are not fully understood. Recently, it was discovered that DNA-binding proteins recognize specific binding sites to carry out their functions through an indirect readout mechanism by recognizing and capturing DNA conformational flexibility and deformation. High throughput DNA microarray-based methods that provide large-scale protein-DNA binding information have shown effective and comprehensive analysis of protein DNA binding affinities, but do not provide information of DNA conformational changes in specific protein-DNA complexes. Building on the high-throughput capability of DNA microarrays, we demonstrate a quantitative approach that simultaneously measures the amount of protein binding to DNA and nanometer-scale DNA conformational change induced by protein binding in a microarray format. Both measurements rely on spectral interferometry on a layered substrate using a single optical instrument in two distinct modalities. In the first modality, we quantitate the amount of binding of protein to surface-immobilized DNA in each DNA spot using a label-free spectral reflectivity technique that accurately measures the surface densities of protein and DNA accumulated on the substrate. In the second modality, for each DNA spot, we simultaneously measure DNA conformational change using a fluorescence vertical sectioning technique that determines average axial height of fluorophores tagged to specific nucleotides of the surface-immobilized DNA. The approach presented in this paper, when combined with current high-throughput DNA microarray-based technologies, has the potential to serve as a rapid and simple method for quantitative and large-scale characterization of conformational specific protein-DNA interactions. PMID- 26890965 TI - Induction docetaxel and S-1 followed by concomitant radiotherapy with low-dose daily cisplatin in locally advanced head and neck carcinoma. AB - BACKGROUND: The purpose of this study was to assess the efficacy and safety of induction chemotherapy with docetaxel-S-1, and radiotherapy (RT) with concurrent daily cisplatin in locally advanced head and neck carcinoma. METHOD: Fifty patients received 2 cycles of induction chemotherapy with induction chemotherapy with docetaxel and S-1, followed by 7 cycles of RT with concurrent daily cisplatin. RESULTS: The most frequent grade 3 to 4 hematologic toxicity was neutropenia (14%). Forty of 50 patients who completed induction chemotherapy with docetaxel and S-1 subsequently started RT with concurrent daily cisplatin, all within 3 to 4 weeks after the start of the second cycle of induction chemotherapy with docetaxel and S-1. The best response to induction chemotherapy with docetaxel and S-1 and after completion of RT with concurrent daily cisplatin was partial response (PR) in 52.5% and complete response in 47.5%, respectively. With a median follow-up of 61 months, 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 65.7%, respectively. CONCLUSION: Administration of induction chemotherapy with docetaxel and S-1 before RT with concurrent daily cisplatin chemoradiotherapy (CRT) resulted in a high response rate with good tolerability, and did not compromise subsequent CRT. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1653-E1659, 2016. PMID- 26890967 TI - Design and Synthesis of Carbon Nanotube Segments. AB - The selective and predictable synthesis of structurally uniform carbon nanotubes (CNTs) represents a long-standing goal in both nanocarbon science and synthetic organic chemistry. This Review focuses on synthetic studies toward the controlled synthesis of CNTs with single chirality through the organic synthesis of CNT segments and the organic template assisted growth of CNTs. PMID- 26890966 TI - Neuroblastoma With Intraspinal Extension: Health Problems in Long-Term Survivors. AB - AIM: To evaluate the prevalence of health problems in 5-year survivors treated for neuroblastoma (NBL) with intraspinal extension. PATIENTS AND METHODS: Retrospective, single center cohort study (using data from Childhood Cancer Registry and medical records) of patients treated for NBL with intraspinal extension (between 1980 and 2007) who survived >= 5 years after diagnosis. Health problems were graded according to the Common Terminology Criteria for Adverse Events (CTCAEv.3.0). RESULTS: All eligible patients (n = 19) were included (n = 7 no neurological symptoms at diagnosis), median age at diagnosis was 1.2 years (0.6-10.8 years), and median follow-up time was 15.6 years (6.3-29.5 years). Ninety-five percent of survivors had >=1 health problem and 48% of survivors had >=4 health problem with a mean of 3.8 per survivor. Fifty-three percent of survivors had at least one severe (grade 3) or life-threatening/disabling (grade 4) health problem. The three most prevalent health problems were kyphosis and/or scoliosis (68% of patients), motor neuropathy (32% of patients), and sensory neuropathy (26% of patients). Of the 13 patients who underwent a laminectomy, 54% (seven of 13) developed a grade 3 and 23% (three of 13) developed a grade 4 health problem. Among six patients, without laminectomy, 17% developed (one of six) a grade 3 and in 17% developed (one of six) a grade 4 health problem. CONCLUSIONS: Ninety-five percent of 5-year survivors treated for a childhood intraspinal NBL have health problems. The high prevalence of grade 3 and 4 health problems (especially in the laminectomy group) emphasizes the importance of specialized long-term multidisciplinary follow-up and identifies optimal treatment with limited morbidity and maximal efficacy. PMID- 26890969 TI - Explosive Resistance Training Increases Rate of Force Development in Ankle Dorsiflexors and Gait Function in Adults With Cerebral Palsy. AB - Kirk, H, Geertsen, SS, Lorentzen, J, Krarup, KB, Bandholm, T, and Nielsen, JB. Explosive resistance training increases rate of force development in ankle dorsiflexors and gait function in adults with cerebral palsy. J Strength Cond Res 30(10): 2749-2760, 2016-Alterations in passive elastic properties of muscles and reduced ability to quickly generate muscle force contribute to impaired gait function in adults with cerebral palsy (CP). In this study, we investigated whether 12 weeks of explosive and progressive heavy-resistance training (PRT) increases rate of force development of ankle dorsiflexors (RFDdf), improves gait function, and affects passive ankle joint stiffness in adults with CP. Thirty five adults (age: 36.5; range: 18-59 years) with CP were nonrandomly assigned to a PRT or nontraining control (CON) group in this explorative trial. The PRT group trained ankle dorsiflexion, plantarflexion, leg press, hamstring curls, abdominal curls, and back extension 3 days per week for 12 weeks, with 3 sets per exercise and progressing during the training period from 12 to 6 repetition maximums. RFDdf, 3-dimensional gait analysis, functional performance, and ankle joint passive and reflex-mediated muscle stiffness were evaluated before and after. RFDdf increased significantly after PRT compared to CON. PRT also caused a significant increase in toe lift late in swing and a significantly more dorsiflexed ankle joint at ground contact and during stance. The increased toe lift amplitude was correlated to the increased RFDdf (r = 0.73). No other between group differences were observed. These findings suggest that explosive PRT may increase RFDdf and facilitate larger range of movement in the ankle joint during gait. Explosive PRT should be tested in clinical practice as part of a long-term training program for adults with CP. PMID- 26890968 TI - Relationship Between Maximum Aerobic Speed Performance and Distance Covered in Rugby Union Games. AB - Swaby, R, Jones, PA, and Comfort, P. Relationship between maximum aerobic speed performance and distance covered in rugby union games. J Strength Cond Res 30(10): 2788-2793, 2016-Researchers have shown a clear relationship between aerobic fitness and the distance covered in professional soccer, although no research has identified such a relationship in rugby union. Therefore, the aim of the study was to identify whether there was a relationship between maximal aerobic speed (MAS) and the distance covered in rugby union games. Fourteen professional rugby union players (age = 26 +/- 6 years, height = 1.90 +/- 0.12 m, mass = 107.1 +/- 24.1 kg) participated in this investigation. Each player performed a MAS test on 3 separate occasions during the preseason, to determine reliability and provide baseline data, and participated in 6 competitive games during the early stages of the season. Game data were collected using global positioning system technology. No significant difference (p > 0.05) in total distance covered was observed between games. Relationships between players' MAS and the average distance covered from 6 competitive games were explored using Pearson's correlation coefficients, with MAS performance showing a strong relationship with distance covered during match play (r = 0.746, p < 0.001). Significantly greater (p = 0.001, Cohen's d = 2.29) distances were covered by backs (6,544 +/- 573 m) compared with the forwards (4,872 +/- 857 m) during a game. Similarly, backs recorded a significantly (p = 0.001, Cohen's d = 2.20) higher MAS (4.9 +/- 0.13 m.s) compared with the forwards (4.2 +/- 0.43 m.s). Results of the study illustrate the importance of developing high levels of aerobic fitness to increase the distance that the athlete covers in the game. PMID- 26890970 TI - Physical Attributes and NFL Combine Performance Tests Between Italian National League and American Football Players: A Comparative Study. AB - Vitale, JA, Caumo, A, Roveda, E, Montaruli, A, La Torre, A, Battaglini, CL, and Carandente, F. Physical attributes and NFL Combine performance tests between Italian National League and American football players: a comparative study. J Strength Cond Res 30(10): 2802-2808, 2016-The purpose of this study was to examine anthropometric measurements and the results of a battery of performance tests administered during the National Football League (NFL) Combine between American football players who were declared eligible to participate in the NFL Combine and football players of a top Italian team (Rhinos Milan). Participants (N = 50) were categorized by position into 1 of 3 groups based on playing position: skill players (SP) included wide receivers, cornerbacks, free safeties, strong safeties, and running backs; big skill players (BSP) consisted of fullbacks, linebackers, tight ends, and defensive ends; lineman (LM) included centers, offensive guards, offensive tackles, and defensive tackles. A 1-way analysis of variance followed by the Tukey-Kramer post hoc test was used for comparisons between Italian players by playing position. Ninety-five percent CIs were used for comparisons between American and Italian football for the NFL Combine performance tests. Significant differences for all the variables between the 3 playing categories were observed among the Italian players; LM had higher anthropometric and body composition values than SP (p < 0.001) and BSP (p < 0.001), whereas LM performed significantly worse in the physical tests, except for the 225-lb bench press test when compared with SP (p < 0.002). American football players presented significantly higher anthropometric values and test performance scores when compared with Italian players. Administrators of professional football teams in Italy need to improve the player's physical attributes, so the gap that currently exists between American and Italian players can be reduced, which could significantly improve the quality of American football in Italy. PMID- 26890971 TI - Acute Anabolic Response and Muscular Adaptation After Hypertrophy-Style and Strength-Style Resistance Exercise. AB - Gonzalez, AM. Acute anabolic response and muscular adaptation after hypertrophy style and strength-style resistance exercise. J Strength Cond Res 30(10): 2959 2964, 2016-Resistance training paradigms are often divided into protocols designed to promote an increase in either hypertrophy or strength. Hypertrophy style protocols (HYPs) typically involve greater volume (3-6 sets; 8-12 repetitions), moderate intensities (<85% 1 repetition maximum [1RM]), and short rest intervals (30-90 seconds), whereas strength-style protocols (STRs) typically involve higher intensities (>=85% 1RM), low volumes (2-6 sets; <=6 repetitions), and longer rest intervals (3-5 minutes). However, the literature supporting such classifications is surprisingly sparse in trained individuals, and the distinct classifications of such protocols may be an oversimplification. Thus, the purpose of this review was to examine the acute anabolic responses and training-induced muscular adaptations after HYP and STR styles of resistance exercise in trained individuals. Despite the classification of training paradigms, HYP and STR resistance training routines appear to elicit similar magnitudes of muscle growth, although STR routines appear to be more conducive to increasing strength in resistance-trained individuals. Current evidence suggests that the classification of HYP and STR is an oversimplification, and practitioners are advised to look beyond the classification of resistance exercise protocols when aiming to elicit specific physiological responses. PMID- 26890972 TI - Comparing the Effectiveness of a Short-Term Vertical Jump vs. Weightlifting Program on Athletic Power Development. AB - Teo, SYM, Newton, MJ, Newton, RU, Dempsey, AR, and Fairchild, TJ. Comparing the effectiveness of a short-term vertical jump vs. weightlifting program on athletic power development. J Strength Cond Res 30(10): 2741-2748, 2016-Efficient training of neuromuscular power and the translation of this power to sport-specific tasks is a key objective in the preparation of athletes involved in team-based sports. The purpose of this study was to compare changes in center of mass (COM) neuromuscular power and performance of sport-specific tasks after short-term (6 week) training adopting either Olympic-style weightlifting (WL) exercises or vertical jump (VJ) exercises. Twenty-six recreationally active men (18-30 years; height: 178.7 +/- 8.3 cm; mass: 78.6 +/- 12.2 kg) were randomly allocated to either a WL or VJ training group and performance during the countermovement jump (CMJ), squat jump (SJ), depth jump (DJ), 20-m sprint, and the 5-0-5 agility test assessed pre and posttraining. Despite the WL group demonstrating larger increases in peak power output during the CMJ (WL group: 10% increase, d = 0.701; VJ group: 5.78% increase, d = 0.328) and SJ (WL group: 12.73% increase, d = 0.854; VJ group: 7.27% increase, d = 0.382), no significant between-group differences were observed in any outcome measure studied. There was a significant main effect of time observed for the 3 VJs (CMJ, SJ, and DJ), 0- to 5-m and 0- to 20-m sprint times, and the 5-0-5 agility test time, which were all shown to improve after the training (all main effects of time p < 0.01). Irrespective of the training approach adopted by coaches or athletes, addition of either WL or VJ training for development of power can improve performance in tasks associated with team-based sports, even in athletes with limited preseason training periods. PMID- 26890973 TI - Do Running Kinematic Characteristics Change over a Typical HIIT for Endurance Runners? AB - Garcia-Pinillos, F, Soto-Hermoso, VM, and Latorre-Roman, PA. Do running kinematic characteristics change over a typical HIIT for endurance runners?. J Strength Cond Res 30(10): 2907-2917, 2016-The purpose of this study was to describe kinematic changes that occur during a common high-intensity intermittent training (HIIT) session for endurance runners. Twenty-eight male endurance runners participated in this study. A high-speed camera was used to measure sagittal plane kinematics at the first and the last run during a HIIT (4 * 3 * 400 m). The dependent variables were spatial-temporal variables, joint angles during support and swing, and foot strike pattern. Physiological variables, rate of perceived exertion, and athletic performance were also recorded. No significant changes (p >= 0.05) in kinematic variables were found during the HIIT session. Two cluster analyses were performed, according to the average running pace-faster vs. slower, and according to exhaustion level reached-exhausted group vs. nonexhausted group (NEG). At first run, no significant differences were found between groups. As for the changes induced by the running protocol, significant differences (p <= 0.05) were found between faster and slower athletes at toe-off in thetahip and thetaknee, whereas some changes were found in NEG in thetahip during toe-off (+4.3 degrees ) and thetaknee at toe-off (-5.2 degrees ) during swing. The results show that a common HIIT session for endurance runners did not consistently or substantially perturb the running kinematics of trained male runners. Additionally, although some differences between groups have been found, neither athletic performance nor exhaustion level reached seems to be determinant in the kinematic response during a HIIT, at least for this group of moderately trained endurance runners. PMID- 26890975 TI - Postactivation Potentiation of Horizontal Jump Performance Across Multiple Sets of a Contrast Protocol. AB - Seitz, LB, Mina, MA, and Haff, GG. Postactivation potentiation of horizontal jump performance across multiple sets of a contrast protocol. J Strength Cond Res 30(10): 2733-2740, 2016-This study determined whether a postactivation potentiation (PAP) effect could be elicited across multiple sets of a contrast PAP protocol. Fourteen rugby league players performed a contrast PAP protocol comprising 4 sets of 2 paused box squats accommodated with bands alternated with 2 standing broad jumps. The rest period between the squats and the jumps and between the sets was 90 seconds. A control protocol with standing broad jumps only was performed on a separate session. A standing broad jump was performed ~2 minutes before each protocol and served as a baseline measurement. Standing broad jump distance was significantly greater (4.0 +/- 3.4% to 5.7 +/- 4.7%) than baseline during the 4 sets of the contrast PAP protocol with the changes being medium in the first, second, and fourth sets (effect size [ES]: 0.58, 0.67, and 0.69, respectively) and large for the third set (ES: 0.81). Conversely, no PAP effect was observed in the control protocol. Additionally, the stronger players displayed a larger PAP effect during each of the 4 sets of the contrast PAP protocol (Cohen's d: 0.28-1.68) and a larger mean effect across these 4 sets (Cohen's d: 1.29). Horizontal jump performance is potentiated after only 90 seconds of rest after an accommodating exercise, and this PAP effect can be elicited across 4 sets. Additionally, the PAP response is largely mediated by the individual's strength level. These results are of great importance for coaches seeking to incorporate PAP complexes involving horizontal jumps in their training programs. PMID- 26890974 TI - Effect of Coffee and Caffeine Ingestion on Resistance Exercise Performance. AB - Richardson, DL and Clarke, ND. Effect of coffee and caffeine ingestion on resistance exercise performance. J Strength Cond Res 30(10): 2892-2900, 2016-The aim of the present study was to determine the effect of ingesting caffeine dose matched anhydrous caffeine, coffee, or decaffeinated coffee plus anhydrous caffeine during resistance exercise on performance. Nine resistance-trained men (mean +/- SD: age, 24 +/- 2 years; weight, 84 +/- 8 kg; height, 180 +/- 8 cm) completed a squat and bench press exercise protocol at 60% 1 repetition maximum until failure on 5 occasions consuming 0.15 g.kg caffeinated coffee (COF), 0.15 g.kg decaffeinated coffee (DEC), 0.15 g.kg decaffeinated coffee plus 5 mg.kg anhydrous caffeine (D + C), 5 mg.kg anhydrous caffeine (CAF), or a placebo (PLA). Felt arousal and rating of perceived exertion (RPE) were used to assess perceptual variables and heart rate (HR) to assess physiological responses between trials. There were significant differences in total weight lifted for the squat between conditions (p < 0.01; (Equation is included in full-text article.)= 0.54) with a greater amount lifted during D + C compared with DEC (p < 0.01), CAF (p <= 0.05), and PLA (p <= 0.05) conditions. Total weight lifted during the COF condition was significantly greater than that lifted under PLA (p < 0.01), although not significantly greater than the amount of weight lifted during the DEC condition (p = 0.082). No significant differences were observed in total weight lifted in the bench press protocol between conditions (p = 0.186; (Equation is included in full-text article.)= 0.17). Significant differences in HR (p < 0.01; (Equation is included in full-text article.)= 0.39) but not RPE (squat: p = 0.690; (Equation is included in full-text article.)= 0.07; bench press: p = 0.165; (Equation is included in full-text article.)= 0.18) and felt arousal (p = 0.056; (Equation is included in full-text article.)= 0.24) were observed between conditions. Coffee and decaffeinated coffee plus caffeine have the ability to improve performance during a resistance exercise protocol, although possibly not over multiple bouts. PMID- 26890976 TI - Periodization Training Focused on Technical-Tactical Ability in Young Soccer Players Positively Affects Biochemical Markers and Game Performance. AB - Aquino, RLQT, Cruz Goncalves, LG, Palucci Vieira, LH, Oliveira, LP, Alves, GF, Pereira Santiago, PR, and Puggina, EF. Periodization training focused on technical-tactical ability in young soccer players positively affects biochemical markers and game performance. J Strength Cond Res 30(10): 2723-2732, 2016-The aim of this study was to investigate the effects of 22 weeks of periodized training, with an emphasis on technical-tactical ability, on indirect markers of muscle damage, and the on-field performance of young soccer players. Fifteen players (age 15.4 +/- 0.2 years, height 172.8 +/- 3.6 cm; body mass 61.9 +/- 2.9 kg; % fat 11.7 +/- 1.6; V[Combining Dot Above]O2max 48.67 +/- 3.24 ml.kg.min) underwent 4 stages of evaluation: prepreparatory stage-T0; postpreparatory stage-T1; postcompetitive stage I-T2 and; postcompetitive stage II-T3. The plasmatic activity of creatine kinase (CK) and lactate dehydrogenase (LDH) were evaluated, as well as the on-field performance (movement patterns, tactical variables). Regarding the plasmatic activity of CK and LDH, there was a significant reduction (p <= 0.05) throughout the periodization training (T0: 350 U.L; T3: 150 U.L). Significant increases were observed (p <= 0.05) in the intensity of the game, high-intensity activities (HIA) (T0: 22%; T3: 27%), maximum speed (T0: 30 km.h; T3: 34 km.h) and tactical performance, team surface area (T0: 515 m; T3: 683 m), and spread (T0: 130 m; T3: 148 m). In addition, we found significant inverse correlations between the percentage variation of T0 to T3 in CK and LDH activities with percentage variation in high-intensity running (r = -0.85; p <= 0.05 and r = -0.84; p < 0.01, respectively) and HIA (r = -0.71 and r = -0.70; p <= 0.05, respectively) during the matches. We concluded that there was reduced activity in biochemical markers related to muscle damage, as well as increases in game high-intensity performance and the tactical performance of the study participants. Furthermore, players who showed greater reduction in plasma activity of CK and LDH also obtained greater increases in-game high-intensity performance along the periodization. These results may contribute to the expansion and future consolidation of the knowledge of coaches and sport scientists to develop effective methodologies for training in soccer. PMID- 26890977 TI - A surprising mediator of oxidative DNA damage. PMID- 26890979 TI - Nickel-Catalyzed Asymmetric Alkene Hydrogenation of alpha,beta-Unsaturated Esters: High-Throughput Experimentation-Enabled Reaction Discovery, Optimization, and Mechanistic Elucidation. AB - A highly active and enantioselective phosphine-nickel catalyst for the asymmetric hydrogenation of alpha,beta-unsaturated esters has been discovered. The coordination chemistry and catalytic behavior of nickel halide, acetate, and mixed halide-acetate with chiral bidentate phosphines have been explored and deuterium labeling studies, the method of continuous variation, nonlinear studies, and kinetic measurements have provided mechanistic understanding. Activation of molecular hydrogen by a trimeric (Me-DuPhos)3Ni3(OAc)5I complex was established as turnover limiting followed by rapid conjugate addition of a nickel hydride and nonselective protonation to release the substrate. In addition to reaction discovery and optimization, the previously unreported utility high throughput experimentation for mechanistic elucidation is also described. PMID- 26890980 TI - Altering the Enantioselectivity of Tyrosyl-tRNA Synthetase by Insertion of a Stereospecific Editing Domain. AB - Translation of mRNAs by the ribosome is stereospecific, with only l-amino acids being incorporated into the nascent polypeptide chain. This stereospecificity results from the exclusion of d-amino acids at three steps during protein synthesis: (1) the aminoacylation of tRNA by aminoacyl-tRNA synthetases, (2) binding of aminoacyl-tRNAs to EF-Tu, and (3) recognition of aminoacyl-tRNAs by the ribosome. As a first step toward incorporating d-amino acids during protein synthesis, we have altered the enantioselectivity of tyrosyl-tRNA synthetase. This enzyme is unusual among aminoacyl-tRNA synthetases, as it can aminoacylate tRNA with d-tyrosine (albeit at a reduced rate compared to l-tyrosine). To change the enantioselectivity of tyrosyl-tRNA synthetase, we introduced the post transfer editing domain from Pyrococcus horikoshii phenylalanyl-tRNA synthetase into the connective polypeptide 1 (CP1) domain of Geobacillus stearothermophilus tyrosyl-tRNA synthetase (henceforth designated TyrRS-FRSed). We show that the phenylalanyl-tRNA synthetase editing domain is stereospecific, hydrolyzing l-Tyr tRNA(Tyr), but not d-Tyr-tRNA(Tyr). We further show that inserting the phenylalanyl-tRNA synthetase editing domain into the CP1 domain of tyrosyl-tRNA synthetase decreases the activity of the synthetic site in tyrosyl-tRNA synthetase. This decrease in activity is critical, as it prevents the rate of synthesis from overwhelming the ability of the editing domain to hydrolyze the l Tyr-tRNA(Tyr) product. Overall, inserting the phenylalanyl-tRNA synthetase editing domain results in a 2-fold shift in the enantioselectivity of tyrosyl tRNA synthetase toward the d-Tyr-tRNA(Tyr) product. When a 4-fold excess of d tyrosine is used, approximately 40% of the tRNA(Tyr) is aminoacylated with d tyrosine. PMID- 26890978 TI - The impact and cost-effectiveness of nonavalent HPV vaccination in the United States: Estimates from a simplified transmission model. AB - INTRODUCTION: The objective of this study was to assess the incremental costs and benefits of the 9-valent HPV vaccine (9vHPV) compared with the quadrivalent HPV vaccine (4vHPV). Like 4vHPV, 9vHPV protects against HPV types 6, 11, 16, and 18. 9vHPV also protects against 5 additional HPV types 31, 33, 45, 52, and 58. METHODS: We adapted a previously published model of the impact and cost effectiveness of 4vHPV to include the 5 additional HPV types in 9vHPV. The vaccine strategies we examined were (1) 4vHPV for males and females; (2) 9vHPV for females and 4vHPV for males; and (3) 9vHPV for males and females. In the base case, 9vHPV cost $13 more per dose than 4vHPV, based on available vaccine price information. RESULTS: Providing 9vHPV to females compared with 4vHPV for females (assuming 4vHPV for males in both scenarios) was cost-saving regardless of whether or not cross-protection for 4vHPV was assumed. The cost per quality adjusted life year (QALY) gained by 9vHPV for both sexes (compared with 4vHPV for both sexes) was < $0 (cost-saving) when assuming no cross-protection for 4vHPV and $8,600 when assuming cross-protection for 4vHPV. CONCLUSIONS: Compared with a vaccination program of 4vHPV for both sexes, a vaccination program of 9vHPV for both sexes can improve health outcomes and can be cost-saving. PMID- 26890981 TI - Fundamental Considerations for Biobank Legacy Planning. AB - Biobanking in its various forms is an activity involving the collection of biospecimens and associated data and their storage for differing lengths of time before use. In some cases, biospecimens are immediately used, but in others, they are stored typically for the term of a specified project or in perpetuity until the materials are used up or declared to be of little scientific value. Legacy planning involves preparing for the phase that follows either biobank closure or a significant change at an operational level. In the case of a classical finite collection, this may be brought about by the completion of the initial scientific goals of a project, a loss of funding, or loss of or change in leadership. Ultimately, this may require making a decision about when and where to transfer materials or whether to destroy them. Because biobanking in its entirety is a complex endeavour, legacy planning touches on biobank operations as well as ethical, legal, financial, and governance parameters. Given the expense and time that goes into setting up and maintaining biobanks, coupled with the ethical imperative to appropriately utilize precious resources donated to research, legacy planning is an activity that every biobanking entity should think about. This article describes some of the fundamental considerations for preparing and executing a legacy plan, and we envisage that this article will facilitate dialogue to help inform best practices and policy development in the future. PMID- 26890984 TI - Obesity and post-operative cognitive dysfunction: a systematic review and meta analysis. AB - BACKGROUND: Post-operative cognitive dysfunction, a condition distinct from post operative delirium (POD), occurs frequently after surgery, and is related to dementia and premature death. Obesity increases the risk of late-life cognitive impairment, but little is known about its role in post-operative cognitive dysfunction. We conducted a systematic review and meta-analysis of studies on the association between obesity and risk of post-operative cognitive dysfunction. METHODS: PubMed and the Cochrane Library were systematically searched. Studies were included if they had prospective designs, reported on human adults undergoing surgery, if cognitive function was measured pre- and post-surgery, if obesity, body mass index (BMI) and/or body weight were ascertained, and if associations with post-operative cognitive dysfunction were reported as relative risks or odds ratios. Underweight, weight loss, and post-operative delirium were not considered. RESULTS: Inclusion criteria were met by six articles. Samples totaled 1432 older patients (mean age >=62 years) who were followed up for 24 h to 12 months after surgery. Analysis of studies with obesity defined as a categorical measure found a non-significantly higher risk of post-operative cognitive dysfunction among persons with BMI > 30 kg/m(2) versus <=30 kg/m(2) (relative risk 1.27; 95% confidence interval 0.95, 1.70; p = 0.10). No such associations were found for studies that analysed BMI or body weight continuously as predictors of post-operative cognitive dysfunction (relative risk 0.98 per kg/m(2) ; 95% confidence interval 0.93, 1.03, p = 0.45; relative risk 0.99 per kg; 95% confidence interval 0.89, 1.09; p = 0.83, respectively). CONCLUSIONS: Few studies have addressed the topic, and the results of these studies provide only limited support for an increased risk of post-operative cognitive dysfunction in patients who are obese. Further large-scale, prospective investigations are necessary for clarification. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26890983 TI - Calreticulin variant stratified driver mutational status and prognosis in essential thrombocythemia. AB - About 85% of patients with essential thrombocythemia (ET) harbor one of three driver mutations: JAK2, calreticulin (CALR), and MPL; the remaining ( ~15%) are wild type for all three mutations and are referred to as being "triple negative." Furthermore, CALR mutations in ET are structurally classified as type 1/type 1 like or type 2/type 2-like variants. The objective of the current study was to examine the impact of CALR mutation variant stratified driver mutational status on overall (OS), myelofibrosis-free (MFFS), thrombosis-free, and leukemia-free survival (LFS) in ET; 495 patients (median age 58 years; 61% females) with ET were fully annotated for the their driver mutational status: 321 (65%) harbored JAK2, 109 (22%) CALR, and 12 (2%) MPL mutations and 11% were triple-negative. Among the 109 CALR-mutated cases, 52% were classified as type 1/type 1-like and 48% as type 2/type 2-like. In univariate analysis, triple-negative patients displayed the best and MPL mutated the worst OS (P = 0.007); however, the difference in OS was no longer apparent on multivariable analysis that included age and sex as covariates (P = 0.5). LFS was also similar among the different mutational groups (P = 0.6) whereas MFFS was significantly shorter in MPL-mutated patients on both univariate and multivariable analyses (age-adjusted P = 0.02; HR 7.9, 95% CI 2.0-31.5). Also in multivariable analysis that included thrombosis history, age, and cardiovascular risk factors, the presence of JAK2 or MPL mutations was independently associated with higher risk of thrombosis (P = 0.02; HR 1.9, 95% CI 1.1-3.4). In conclusion, driver mutational status in ET does not appear to influence overall or LFS, even after CALR variant stratification. However, the presence of MPL mutations might be associated with a higher risk of fibrotic transformation and the presence of JAK2/MPL mutations with higher risk of thrombosis. PMID- 26890982 TI - Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection. AB - Candida albicans (CA) is a kind of fungus that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with secreted aspartyl proteinases 2 (Sap2) can prevent the infection, it is proposed to use filamentous phage, a human-safe virus nanofiber specifically infecting bacteria (~900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val-Lys-Tyr-Thr-Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increases the survival rate of CA-infected mice. All these results, along with the fact that the virus nanofibers can be mass-produced by infecting bacteria cost-effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection. PMID- 26890986 TI - Polypharmacy and the use of medications in inpatients with acquired brain injury during post-acute rehabilitation: A cross-sectional study. AB - BACKGROUND: This study assessed the use of medications during inpatient post acute rehabilitation for acquired brain injury (ABI). MATERIALS AND METHODS: All inpatients with ABI undergoing post-acute rehabilitation in centres identified through the roster of the Italian Society for Rehabilitation Medicine were included. A designated physician in each centre collected information through a structured questionnaire. This study calculated (a) prevalence of medication use, (b) logistic regression Odds Ratio (OR), with 95% confidence interval (95% CI), of polypharmacy (>= 6 medications). RESULTS: A total of 484 patients (median age = 52 years, 63.4% men, median time from acute event = 18.5 weeks) were included; 33.8% had Rancho Los Amigos Levels of Cognitive Functioning Scale (RLAS) score 1 2, 8.1% had a score of 7-8, of whom 92.0% received medications, 51.8% had a score of 6-10, of whom 83.9% had at least one psychotropic medication and 66.9% had two or more; 51.8% received anti-epileptics, 32.1% anti-depressants, 14.5% anti psychotics, peaking in RLAS 4 (37.3%) and decreasing in RLAS 7-8. Polypharmacy was directly associated with age (55-64 years, OR = 2.1; 95% CI = 1.1-4.1; >= 65 years, OR = 1.7; 95% CI = 0.9-3.3), inversely with RLAS score (1-2 vs 7-8, OR = 4.3; 95% CI = 1.9-9.8). CONCLUSION: Polypharmacy and concurrent use of psychotropic medications was common, raising concern about drug-drug interactions. Safety and effectiveness of medications should be monitored, particularly when used concurrently. PMID- 26890985 TI - The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano. AB - Kaempferol has been identified as a potential cancer therapeutic agent by an increasing amount of evidences. However, the changes in the topography of cell membrane induced by kaempferol at subcellular- or nanometer-level were still unclear. In this work, the topographical changes of cytomembrane in human cervical cancer cell (SiHa) induced by kaempferol, as well as the role of kaempferol in apoptosis induction and its possible mechanisms, were investigated. At the macro level, MTT assays showed that kaempferol inhibited the proliferation of SiHa cells in a time- and dose-dependent manner. Flow cytometry analysis demonstrated that kaempferol could induce SiHa cell apoptosis, mitochondrial membrane potential disruption, and intracellular free calcium elevation. At the micro level, fluorescence imaging by laser scanning confocal microscopy (LSCM) indicated that kaempferol could also destroy the networks of microtubules. Using high resolution atomic force microscopy (AFM), we determined the precise changes of cellular membrane induced by kaempferol at subcellular or nanometer level. The spindle-shaped SiHa cells shrank after kaempferol treatment, with significantly increased cell surface roughness. These data showed structural characterizations of cellular topography in kaempferol-induced SiHa cell apoptosis and might provide novel integrated information from macro to nano level to assess the impact of kaempferol on cancer cells, which might be important for the understanding of the anti-cancer mechanisms of drugs. SCANNING 38:644-653, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26890987 TI - Serial measurement of type-specific human papillomavirus load enables classification of cervical intraepithelial neoplasia lesions according to occurring human papillomavirus-induced pathway. AB - This retrospective study examined whether human papillomavirus (HPV) type specific viral load changes measured in two or three serial cervical smears are predictive for the natural evolution of HPV infections and correlate with histological grades of cervical intraepithelial neoplasia (CIN), allowing triage of HPV-positive women. A cervical histology database was used to select consecutive women with biopsy-proven CIN in 2012 who had at least two liquid based cytology samples before the diagnosis of CIN. Before performing cytology, 18 different quantitative PCRs allowed HPV type-specific viral load measurement. Changes in HPV-specific load between measurements were assessed by linear regression, with calculation of coefficient of determination (R) and slope. All infections could be classified into one of five categories: (i) clonal progressing process (R>=0.85; positive slope), (ii) simultaneously occurring clonal progressive and transient infection, (iii) clonal regressing process (R>=0.85; negative slope), (iv) serial transient infection with latency [R<0.85; slopes (two points) between 0.0010 and -0.0010 HPV copies/cell/day], and (v) transient productive infection (R<0.85; slope: +/-0.0099 HPV copies/cell/day). Three hundred and seven women with CIN were included; 124 had single-type infections and 183 had multiple HPV types. Only with three consecutive measurements could a clonal process be identified in all CIN3 cases. We could clearly demonstrate clonal regressing lesions with a persistent linear decrease in viral load (R>=0.85; -0.003 HPV copies/cell/day) in all CIN categories. Type specific viral load increase/decrease in three consecutive measurements enabled classification of CIN lesions in clonal HPV-driven transformation (progression/regression) and nonclonal virion-productive (serial transient/transient) processes. PMID- 26890988 TI - T2-Weighted intracranial vessel wall imaging at 7 Tesla using a DANTE-prepared variable flip angle turbo spin echo readout (DANTE-SPACE). AB - PURPOSE: To optimize intracranial vessel wall imaging (VWI) at 7T for sharp wall depiction and high boundary contrast. METHODS: A variable flip angle turbo spin echo scheme (SPACE) was optimized for VWI. SPACE provides black-blood contrast, but has less crushing effect on cerebrospinal fluid (CSF). However, a delay alternating with nutation for tailored excitation (DANTE) preparation suppresses the signal from slowly moving spins of a few mm per second. Therefore, we optimized a DANTE-preparation module for 7T. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and signal ratio for vessel wall, CSF, and lumen were calculated for SPACE and DANTE-SPACE in 11 volunteers at the middle cerebral artery (MCA). An exemplar MCA stenosis patient was scanned with DANTE-SPACE. RESULTS: The 7T-optimized SPACE sequence improved the vessel wall point-spread function by 17%. The CNR between the wall and CSF was doubled (12.2 versus 5.6) for the DANTE-SPACE scans compared with the unprepared SPACE. This increase was significant in the right hemisphere (P = 0.016), but not in the left (P = 0.090). The CNR between wall and lumen was halved, but remained at a high value (24.9 versus 56.5). CONCLUSION: The optimized SPACE sequence improves VWI at 7T. Additional DANTE preparation increases the contrast between the wall and CSF. Increased outer boundary contrast comes at the cost of reduced inner boundary contrast. Magn Reson Med 77:655-663, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID- 26890990 TI - Selective Generation of the Radical Cation Isomers [CH3CN](*+) and [CH2CNH](*+) via VUV Photoionization of Different Neutral Precursors and Their Reactivity with C2H4. AB - Experimental and theoretical studies have been carried out to demonstrate the selective generation of two different C2H3N(+) isomers, namely, the acetonitrile [CH3CN](*+) and the ketenimine [CH2CNH](*+) radical cations. Photoionization and dissociative photoionization experiments from different neutral precursors (acetonitrile and butanenitrile) have been performed using vacuum ultraviolet (VUV) synchrotron radiation in the 10-15 eV energy range, delivered by the DESIRS beamline at the SOLEIL storage ring. For butanenitrile (CH3CH2CH2CN) an experimental ionization threshold of 11.29 +/- 0.05 eV is obtained, whereas the appearance energy for the formation of [CH2CNH](*+) fragments is 11.52 +/- 0.05 eV. Experimental findings are fully supported by theoretical calculations at the G4 level of theory (ZPVE corrected energies at 0 K), giving a value of 11.33 eV for the adiabatic ionization energy of butanenitrile and an exothermicity of 0.49 for fragmentation into [CH2CNH](*+) plus C2H4, hampered by an energy barrier of 0.29 eV. The energy difference between [CH3CN](*+) and [CH2CNH](*+) is 2.28 eV (with the latter being the lowest energy isomer), and the isomerization barrier is 0.84 eV. Reactive monitoring experiments of the [CH3CN](*+) and [CH2CNH](*+) isomers with C2H4 have been performed using the CERISES guided ion beam tandem mass spectrometer and exploiting the selectivity of ethylene that gives exothermic charge exchange and proton transfer reactions with [CH3CN](*+) but not with [CH2CNH](*+) isomers. In addition, minor reactive channels are observed leading to the formation of new C-C bonds upon reaction of [CH3CN](*+) with C2H4, and their astrochemical implications are briefly discussed. PMID- 26890989 TI - Suspected Rabies in Humans and Animals, Laikipia County, Kenya. PMID- 26890991 TI - Enhanced Antitumor Activity of EGFP-EGF1-Conjugated Nanoparticles by a Multitargeting Strategy. AB - Tumor stromal cells have been increasingly recognized to interact with tumor parenchyma cells and promote tumor growth. Therefore, we speculated that therapeutics delivery to both parenchyma cells and stromal cells simultaneously might treat a tumor more effectively. Tissue factor (TF) was shown to be extensively located in a tumor and was abundantly sited in both tumor parenchyma cells and stromal cells including neo-vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages, indicating it might function as a favorable target for drug delivery to multiple cell types simultaneously. EGFP EGF1 is a fusion protein derived from factor VII, the natural ligand of TF. It retains the specific TF binding capability but does not cause coagulation. In the present study, a nanoparticle modified with EGFP-EGF1 (ENP) was constructed as a multitargeting drug delivery system. The protein binding experiment showed EGFP EGF1 could bind well to A549 tumor cells and other stromal cells including neo vascular cells, tumor-associated fibroblasts, and tumor-associated macrophages. Compared with unmodified nanoparticles (NP), ENP uptake by A549 cells and those stromal cells was significantly enhanced but inhibited by excessive free EGFP EGF1. In addition, ENP induced more A549 tumor cell apoptosis than Taxol and NP when paclitaxel (PTX) was loaded. In vivo, ENP accumulated more specially in TF overexpressed A549 tumors by in vivo imaging, mainly regions unoccupied by factor VII and targeted tumor parenchyma cells as well as different types of stromal cells by immunofluorescence staining. Treatment with PTX-loaded ENP (ENP-PTX) significantly reduced the A549 tumor growth in nude mice while NP-PTX- and Taxol treated mice had lower response to the therapy. Furthermore, H&E and TUNEL staining revealed that ENP-PTX induced more severe tumor necrosis and more extensive cell apoptosis. Altogether, the present study demonstrated that ENP could target multiple key cell types in tumors through TF, which could be utilized to improve the therapeutic effect of anticancer drugs. PMID- 26890992 TI - Designed DNA Surfaces for in Vitro Modulation of Natural Killer Cells. AB - Natural killer (NK) cells are at the junction of the innate and the adaptive immune response and play a very important role in host defense against viral infections and cancer. They have numerous cell surface receptors that activate or inhibit various intracellular signaling cascades that are then integrated to determine the functional activity of these cells. Here we present a surface-based approach that aims to tackle the largely unknown molecular mechanisms of signal integration. We use DNA microarrays containing capture oligonucleotides for the DNA-directed immobilization (DDI) of oligonucleotide-tagged alphaCD16 antibodies as ligands for NK cells. We demonstrate that the resulting surfaces can be gradually tuned in terms of ligand density to trigger the activation of living NK cells, as evidenced by degranulation, the release of cytokines, and intracellular Ca(2+) flux, measured at the level of single cells. PMID- 26890993 TI - In Vitro Photoirradiation System for Simultaneous Irradiation with Different Light Doses at a Fixed Temperature. AB - OBJECTIVE: In this work an irradiance and temperature controlled in-vitro system for conducting investigations in PDT and phototherapy is presented. BACKGROUND DATA: The development of new light sources has caused a considerable increase in research and application of several photodynamic (PDT) therapeutic methods, as well as other light-based therapeutic techniques. However, further work is needed to fully understand and elucidate the mechanisms as well as to increase the effectiveness of PDT. Nowadays, there are no commercial systems to perform automated light exposure experiments with cultured cells. Also, there are very few reports of similar photoirradiation systems. MATERIALS AND METHODS: The system is composed of 24 independent light-emitting diodes that can be used to irradiate separate wells in a microwell plate. The system includes a module to measure changes in temperature within each irradiated well without contact. The light sources are placed on a plate that can easily be changed in order to irradiate at different wavelengths. The performance of the system is fully controlled with a computer, and all the experimental data are properly recorded. RESULTS: The design, construction, operation, and a full characterization of the system are presented. CONCLUSIONS: A novel fully automated photoirradiation system has been developed. The system allows the design of the experiments in this area with precise dosimetry, temperature, and irradiation regime controls reducing manipulation of the samples and saving time. PMID- 26890995 TI - Synthesis of Glc1Man9-Glycoprotein Probes by a Misfolding/Enzymatic Glucosylation/Misfolding Sequence. AB - Glycoproteins in non-native conformations are often toxic to cells and may cause diseases, thus the quality control (QC) system eliminates these unwanted species. Lectin chaperone calreticulin and glucosidase II, both of which recognize the Glc1 Man9 oligosaccharide on glycoproteins, are important components of the glycoprotein QC system. Reported herein is the preparation of Glc1 Man9 glycoproteins in both native and non-native conformations by using the following sequence: misfolding of chemically synthesized Man9 -glycoprotein, enzymatic glucosylation, and another misfolding step. By using synthetic glycoprotein probes, calreticulin was found to bind preferentially to a hydrophobic non-native glycoprotein whereas glucosidase II activity was not affected by glycoprotein conformation. The results demonstrate the ability of chemical synthesis to deliver homogeneous glycoproteins in several non-native conformations for probing the glycoprotein QC system. PMID- 26890996 TI - Novel application of bacteriophage for controlling foaming in wastewater treatment plant- an eco-friendly approach. AB - This addendum to "Novel application of bacteriophage for controlling foaming in wastewater treatment plant- an eco-friendly approach " includes characteristics of the phages NOC1, NOC2 and NOC3 not discussed in the previous paper. The phage adsorption and host interaction properties, their sensitivity to pH and temperature are inferred. NOC2 is seen to be more temperature resistant while others are not. All the phages show pH sensitivity. There is a variance observed in the behavior of these phages. Also, applicability of the phage based system to large scale reactors is studied and discussed here. PMID- 26890997 TI - Combining intra-dialytic exercise and nutritional supplementation in malnourished older haemodialysis patients: Towards better quality of life and autonomy. AB - Protein-energy wasting (PEW), defined as a loss of body protein mass and fuel reserves, is a powerful predictor of adverse outcomes in haemodialysis (HD) patients. Robust arguments suggest that intra-dialytic exercise, combined with oral/parenteral nutrition, enhances the effect of nutritional interventions in HD patients. This pilot randomized controlled trial investigated the feasibility and the effects of a 6 month intra-dialytic cycling program combined to a nutritional support on PEW, physical functioning (gait, balance, muscle strength) and quality of life (QoL) in older HD patients (mean age 69.7 +/- 14.2 years).Twenty-one patients fulfilling diagnostic criteria of PEW were randomly assigned to Nutrition-Exercise group (GN-Ex , n = 10) or Nutrition group (GN , n = 11). Both groups received nutritional supplements in order to reach recommended protein and energy intake goals. In addition GN-Ex completed a cycling program. No significant difference between groups was found in the number of patients having reached remission of PEW. Likewise, no change was observed in serum-albumin, prealbumin, C-reactive protein, body mass index, lean- and fat-tissue index, or quadriceps force. Interestingly, we found positive effects of exercise on physical function and QoL for the GN-Ex , as evidenced by a significant improvement in the 6-min walk test (+22%), the absence of decline in balance (unlike the GN ), and a noteworthy increase in QoL (+53%). Combining intra dialytic exercise and nutrition in HD patients is feasible, and well accepted, improves physical function and QoL but it appears not to have the potential to reverse PEW. PMID- 26890998 TI - Single Residue Substitutions That Confer Voltage-Gated Sodium Ion Channel Subtype Selectivity in the NaV1.7 Inhibitory Peptide GpTx-1. AB - There is interest in the identification and optimization of new molecular entities selectively targeting ion channels of therapeutic relevance. Peptide toxins represent a rich source of pharmacology for ion channels, and we recently reported GpTx-1 analogs that inhibit NaV1.7, a voltage-gated sodium ion channel that is a compelling target for improved treatment of pain. Here we utilize multi attribute positional scan (MAPS) analoging, combining high-throughput synthesis and electrophysiology, to interrogate the interaction of GpTx-1 with NaV1.7 and related NaV subtypes. After one round of MAPS analoging, we found novel substitutions at multiple residue positions not previously identified, specifically glutamic acid at positions 10 or 11 or lysine at position 18, that produce peptides with single digit nanomolar potency on NaV1.7 and 500-fold selectivity against off-target sodium channels. Docking studies with a NaV1.7 homology model and peptide NMR structure generated a model consistent with the key potency and selectivity modifications mapped in this work. PMID- 26891000 TI - Immunomodulatory Effects of Nontoxic Glycoprotein Fraction Isolated from Rice Bran. AB - Rice bran, a by-product of brown rice milling, is a rich source of dietary fiber and protein, and its usage as a functional food is expected to increase. In this study, immunomodulatory effects of glycoprotein obtained from rice bran were studied in normal mice and mouse models of cyclophosphamide-induced immunosuppression. We prepared glycoprotein from rice bran by using ammonium precipitation and anion chromatography techniques. Different doses of glycoprotein from rice bran (10, 25, and 50 mg/kg) were administered orally for 28 days. On day 21, cyclophosphamide at a dose of 100 mg/kg was administered intraperitoneally. Glycoprotein from rice bran showed a significant dose dependent restoration of the spleen index and white blood cell count in the immunocompromised mice. Glycoprotein from rice bran affected the immunomodulatory function by inducing the proliferation of splenic lymphocytes, which produce potential T and B cells. Moreover, it prevented cyclophosphamide-induced damage of Th1-type immunomodulatory function through enhanced secretion of Th1-type cytokines (interferon-gamma and interleukin-12). These results indicate that glycoprotein from rice bran significantly recovered cyclophosphamide-induced immunosuppression. Based on these data, it was concluded that glycoprotein from rice bran is a potent immunomodulator and can be developed to recover the immunity of immunocompromised individuals. PMID- 26890999 TI - Depression Change Profiles in Adolescents Treated for Comorbid Depression/Substance Abuse and Profile Membership Predictors. AB - Using data from a randomized trial in which adolescents with depressive and substance use disorders (SUD) received treatments for both disorders in either a sequenced or coordinated manner, we (a) determine the number and nature of depression response profiles through 1-year posttreatment and (b) examine whether 8 previously identified factors predict profile membership. There were 170 adolescents (M age = 16.4 years; 22% female; 28% Hispanic, 61% Non-Hispanic White) with comorbid depressive disorder/SUD randomized to one of three sequences of receiving the Adolescent Coping With Depression Course and Functional Family Therapy for SUD (depression treatment followed by SUD treatment; SUD treatment followed by depression treatment; coordinated treatment). Depression was assessed at 7 points from baseline to 1-year follow-up. A 4-class solution fit the data best, with groups labeled Mildly Depressed Responders (57.1%), Depressed Responders (18.8%), Depressed Non-Responders (12.9%), and Depressed with Recurrence (11.2%). The 4 change profiles differed on indices of all but 1 predictor (age); most differences were driven by lower scores among Mildly Depressed Responders. Profile membership was most strongly predicted by depression severity, cognitive distortions, hopelessness, and global functioning. The strongest predictor of Nonresponse was low family cohesion, whereas Recurrence was associated with hopelessness, suicide attempts, and starting treatment near the end of the school year. Most depressed adolescents experienced a positive response that was maintained. Understanding the most common profiles of depression change during and following treatment and the variables that predict change can help improve treatment outcomes and advance tailoring efforts. PMID- 26891001 TI - Comparative Study of Composition, Antioxidant, and Antimicrobial Activities of Essential Oils of Selected Aromatic Plants from Balkan Peninsula. AB - The objective of the present study to perform a comparative analysis of the chemical composition, antioxidant, and antimicrobial activities of the essential oils of plant species Hyssopus officinalis, Achillea grandifolia, Achillea crithmifolia, Tanacetum parthenium, Laserpitium latifolium, and Artemisia absinthium from Balkan Peninsula. The chemical analysis of essential oils was performed by using gas chromatography and gas chromatography-mass spectrometry. Monoterpenes were dominant among the recorded components, with camphor in T. parthenium, A. grandifolia, and A. crithmifolia (51.4, 45.4, and 25.4 %, respectively), 1,8-cineole in H. officinalis, A. grandifolia, and A. crithmifolia (49.1, 16.4, and 14.8 %, respectively), and sabinene in L. latifolium and A. absinthium (47.8 and 21.5 %). The antiradical and antioxidant activities were determined by using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and 2,2-diphenyl-1-picrylhydrazyl radical scavenging methods. The essential oil of A. grandifolia has shown the highest antioxidant activity [IC50 of 33.575 +/- 0.069 mg/mL for 2,2-diphenyl-1-picrylhydrazyl and 2.510 +/- 0.036 mg vitamin C/g for the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assay]. The antimicrobial activity against 16 multiresistant pathogenic bacteria isolated from human source material was tested by the broth microdilution assay. The resulting minimum inhibitory concentration/minimum bactericidal concentration values ranged from 4.72 to 93.2 mg/mL. Therefore, the essential oils of the plant species included in this study may be considered to be prospective natural sources of antimicrobial substances, and may contribute as effective agents in the battle against bacterial multiresistance. PMID- 26891002 TI - Drugs and Drug Candidates from Marine Sources: An Assessment of the Current "State of Play". AB - The potential of the marine environment to produce candidate compounds (structures) as leads to, or even direct drugs from, has been actively discussed for the last 50 or so years. Over this time frame, several compounds have led to drugs, usually in the area of cancer (due to funding sources). This review is designed to show where there have been successes, but also to show that in a number of disease areas, there are structures originally isolated from marine invertebrates and free-living microbes that have potential, but will need to be "adopted" by pharmaceutical houses in order to maximize their potential. PMID- 26891004 TI - Childhood obesity: research as a springboard for physical activity policies. PMID- 26891003 TI - Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. AB - BACKGROUND: Ataxia telangiectasia (AT) is a genetic multisystem disorder, presenting with progressive ataxia, immune deficiency, and propensity toward malignancy. Endocrine abnormalities (growth retardation, reproductive dysfunction, and diabetes) have been described, however detailed information regarding this aspect is lacking. We aimed to characterize endocrine anomalies and growth patterns in a large cohort of AT patients. METHODS: Retrospective study comprising all 52 patients (aged 2-26.2 y) followed at a national AT Clinic. Anthropometric and laboratory measurements were extracted from the charts. RESULTS: Median height-SDS was already subnormal during infancy, remaining negative throughout follow up to adulthood. Height-SDS was more impaired than weight-SDS up to age 4 y, thereafter weight-SDS steadily decreased, resulting in progressively lower BMI-SDS. IGF-I-SDS was low (-1.53 +/- 1.54), but did not correlate with height-SDS. Gonadal failure was present in all 13 females older than 10 y but only in one male. Two patients had diabetes and 10 had dyslipidemia. Vitamin D deficiency was observed in 52.2% of the evaluated patients. CONCLUSION: Our results suggest a primary growth abnormality in AT, rather than secondary to nutritional impairment or disease severity. Sex hormone replacement should be considered for female patients. Vitamin D levels should be followed and supplementation given if needed. PMID- 26891005 TI - From polyadenylation to splicing: Dual role for mRNA 3' end formation factors. AB - Recent genome-wide protein-RNA interaction studies have significantly reshaped our understanding of the role of mRNA 3' end formation factors in RNA biology. Originally thought to function solely in mediating cleavage and polyadenylation of mRNAs during their maturation, 3' end formation factors have now been shown to play a role in alternative splicing, even at internal introns--an unanticipated role for factors thought only to act at the 3' end of the mRNA. Here, we discuss the recent advances in our understanding of the role of 3' end formation factors in promoting global changes in alternative splicing at internal exon-intron junctions and how they act as cofactors for well known splicing regulators. Additionally, we review the mechanism by which these factors affect the recruitment of early intron recognition components to the 5' and 3' splice site. Our understanding of the roles of 3' end formation factors is still evolving, and the final picture might be more complex than originally envisioned. PMID- 26891008 TI - OR2W3 sequence variants are unlikely to cause inherited retinal diseases. AB - Because of its formidable throughput, whole exome sequencing (WES) is significantly increasing the power of investigations in ophthalmic genetics. However, when applied to Mendelian conditions, WES results often contain many false positives, e.g. candidate mutations that are unrelated to the disease. For instance, highly polymorphic genes such as olfactory receptor genes carry a plethora of both common and rare alleles that are part of the normal set of variations of the human genome. Following a WES-based study, the heterozygous missense variant p.R142W in the olfactory receptor gene OR2W3 was recently reported as a pathogenic mutation causing autosomal dominant retinitis pigmentosa (RP). This variant, however, was not scored against data contained in public WES repositories, indicating that p.R142W is present in ~1 in 6500 control individuals. Therefore, if it really was pathogenic, it would be responsible for a percentage of dominant RP cases corresponding to the double of those recorded so far worldwide, or 2/3 of all RP cases (dominant, recessive, and X-linked). We therefore conclude that this sequence variant, and hence the OR2W3 gene, do not cause RP. Prompted by these findings and based on simple principles of population genetics, we suggest that WES studies should consider DNA variants as the possible cause of dominant RP only if they are present in less than 1:100,000 individuals from the general population. In addition, we propose that DNA variants belonging to highly polymorphic genes should be carefully analyzed at the functional level before inferring their pathogenicity, in RP or other genetic diseases. PMID- 26891009 TI - Assessment of the hazard posed by metal forms in water and sediments. AB - This study aimed to describe the prevalence heavy metals (Zn, Cu, Pb, and Cd) forms in the ecosystem of the Utrata river in order to determine the mobile forms and bioavailability of metals. To extract the dissolved forms of metals in the water of the Utrata PHREEQC2 geochemical speciation model was used. The river waters show a high percentage of mobile and eco-toxic forms of Zn, Cu and Pb. The percentage of carbonate forms for all the studied metals was low (<1%). The content of carbonates in the water and the prevailing physical and chemical conditions (pH, hardness, alkalinity) reduce the share of toxic metal forms, which precipitate as hardly soluble carbonate salts of Zn, Cu, Cd and Pb. Cu in the water in 90% of cases appeared in the form of hydroxyl compounds. To identify the forms of metal occurrence in the sediments Tessier's sequential extraction was used, allowing to assay bound metals in five fractions (ion exchange, carbonate, adsorption, organic, residual), whose nature and bioavailability varies in aquatic environments. The study has shown a large share of metals in labile and bioavailable forms. The speciation analysis revealed an absolute dominance of the organic fraction in the binding of Cu and Pb. Potent affinity for this fraction was also exhibited by Cd. The rations of exchangeable Zn and Cu forms in the sediments were similar. Both these metals had the lowest share in the most mobile ion exchange fraction. PMID- 26891010 TI - Evaluating the roles of biotransformation, spatial concentration differences, organism home range, and field sampling design on trophic magnification factors. AB - Trophic magnification factors (TMFs) are field-based measurements of the bioaccumulation behavior of chemicals in food-webs. TMFs can provide valuable insights into the bioaccumulation behavior of chemicals. However, bioaccumulation metrics such as TMF may be subject to considerable uncertainty as a consequence of systematic bias and the influence of confounding variables. This study seeks to investigate the role of systematic bias resulting from spatially-variable concentrations in water and sediments and biotransformation rates on the determination of TMF. For this purpose, a multibox food-web bioaccumulation model was developed to account for spatial concentration differences and movement of organisms on chemical concentrations in aquatic biota and TMFs. Model calculated and reported field TMFs showed good agreement for persistent polychlorinated biphenyl (PCB) congeners and biotransformable phthalate esters (PEs) in a marine aquatic food-web. Model testing showed no systematic bias and good precision in the estimation of the TMF for PCB congeners but an apparent underestimation of model calculated TMFs, relative to reported field TMFs, for PEs. A model sensitivity analysis showed that sampling designs that ignore the presence of concentration gradients may cause systematically biased and misleading TMF values. The model demonstrates that field TMFs are most sensitive to concentration gradients and species migration patterns for substances that are subject to a low degree of biomagnification or trophic dilution. The model is useful in anticipating the effect of spatial concentration gradients on the determination of the TMF; guiding species collection strategies in TMF studies; and interpretation of the results of field bioaccumulation studies in study locations where spatial differences in chemical concentration exist. PMID- 26891006 TI - Innate lymphoid cells in asthma: Will they take your breath away? AB - Asthma is a complex and heterogeneous disease that is characterized by airway hyper-reactivity (AHR) and airway inflammation. Although asthma was long thought to be driven by allergen-reactive TH 2 cells, it has recently become clear that the pathogenesis of asthma is more complicated and associated with multiple pathways and cell types. A very exciting recent development was the discovery of innate lymphoid cells (ILCs) as key players in the pathogenesis of asthma. ILCs do not express antigen receptors but react promptly to "danger signals" from inflamed tissue and produce an array of cytokines that direct the ensuing immune response. The roles of ILCs may differ in distinct asthma phenotypes. ILC2s may be critical for initiation of adaptive immune responses in inhaled allergen driven AHR, but may also function independently of adaptive immunity, mediating influenza-induced AHR. ILC2s also contribute to resolution of lung inflammation through their production of amphiregulin. Obesity-induced asthma is associated with expansion of IL-17A-producing ILC3s in the lungs. Furthermore, ILCs may also contribute to steroid-resistant asthma. Although the precise roles of ILCs in different types of asthma are still under investigation, it is clear that inhibition of ILC function represents a potential target that could provide novel treatments for asthma. PMID- 26891011 TI - Assessment of temperature effect on childhood hand, foot and mouth disease incidence (0-5years) and associated effect modifiers: A 17 cities study in Shandong Province, China, 2007-2012. AB - BACKGROUND: Previous studies examining temperature-disease associations of hand, foot and mouth disease (HFMD) mainly focused on a single city. The results demonstrated great heterogeneity. A multi-city study is necessary to better understand temperature risk on the childhood incidence of HFMD and the associated modified factors. OBJECTIVE: To assess the effect of ambient temperature on childhood HFMD incidence and explore the potential associated effect modifiers in the study area. METHODS: Daily morbidity data and meteorological variables of the 17 cities were collected for the period from 2007 to 2012. Distributed lag non linear model (DLNM) was used to estimate city-specific effects of temperature on HFMD incidence. A multivariate meta-analysis was then applied to pool the estimated city-specific effect. Potential effect modifiers were included in the multivariate meta-regression as meta-predictors. RESULTS: A total of 504,017 childhood HFMD cases were included in the study. The high-incidence period of HFMD was detected in late spring and early summer (April to June). The temperature-disease associations of the 17 cities demonstrated great heterogeneity and the pooled exposure-response curve was an approximately inverted V-shape. Regional indicator, numbers of healthcare institution and annual household income were considered as associated modifiers. CONCLUSION: Our findings can provide a practical reference for the early warning and intervention strategies of HFMD. Different temperature-disease associations among different regions should be considered when formulating and optimizing public health policy. PMID- 26891012 TI - Irrigation salinity hazard assessment and risk mapping in the lower Macintyre Valley, Australia. AB - In the Murray-Darling Basin of Australia, secondary soil salinization occurs due to excessive deep drainage and the presence of shallow saline water tables. In order to understand the cause and best management, soil and vadose zone information is necessary. This type of information has been generated in the Toobeah district but owing to the state border an inconsistent methodology was used. This has led to much confusion from stakeholders who are unable to understand the ambiguity of the results in terms of final overall risk of salinization. In this research, a digital soil mapping method that employs various ancillary data is presented. Firstly, an electromagnetic induction survey using a Geonics EM34 and EM38 was used to characterise soil and vadose zone stratigraphy. From the apparent electrical conductivity (ECa) collected, soil sampling locations were selected and with laboratory analysis carried out to determine average (2-12m) clay and EC of a saturated soil-paste extract (ECe). EM34 ECa, land surface parameters derived from a digital elevation model and measured soil data were used to establish multiple linear regression models, which allowed for mapping of various hazard factors, including clay and ECe. EM38 ECa data were calibrated to deep drainage obtained from Salt and Leaching Fraction (SaLF) modelling of soil data. Expert knowledge and indicator kriging were used to determine critical values where the salinity hazard factors were likely to contribute to a shallow saline water table (i.e., clay <=35%; ECe>2.5dS/m, and deep drainage >100mm/year). This information was combined to produce an overall salinity risk map for the Toobeah district using indicator kriging. The risk map shows potential salinization areas and where detailed information is required and where targeted research can be conducted to monitor soil conditions and water table heights and determine best management strategies. PMID- 26891013 TI - Association between DbetaH 5'-insertion/deletion polymorphism and cognition in patients with chronic schizophrenia. AB - BACKGROUND: Cognitive deficits have been identified as a core feature of patients with schizophrenia. Many genes associated with the dopamine and norepinephrine systems are related to the cognitive deficits of patients with schizophrenia. Dopamine beta-hydroxylase (DbetaH) is a key enzyme that converts dopamine to norepinephrine and for which activity and levels are under strong genetic control. OBJECTIVE: To examine whether the DbetaH 5'-insertion/deletion (Ins/Del) polymorphism influences cognitive function in patients with chronic schizophrenia. METHOD: The presence of the DbetaH 5'-Ins/Del polymorphism was determined in 733 patients with chronic schizophrenia (diagnosed according to DSM IV) and 544 healthy controls using a case-control design. We assessed all of the patients' psychopathology using the Positive and Negative Syndrome Scale (PANSS) and cognition in 540 patients with chronic schizophrenia and 297 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This study was conducted between 2008 and 2011. RESULTS: The allelic and genotypic frequencies of the DbetaH 5'-Ins/Del polymorphism were not significantly different between patients with schizophrenia and healthy controls (both P values > .05). However, the cognitive test scores were significantly lower in patients than in the healthy controls for all scales (all P values < .05), except visuospatial/constructional (P > .05). The attention score significantly differed according to the genotypic group (P < .05) in patients but not in the healthy controls (P > .05). In patients with chronic schizophrenia, the mean +/- SD attention score was lower in the DbetaH 5'-Del/Del genotype (65.7 +/- 16.8) than in the DbetaH 5'-Ins/Del genotype (71.4 +/- 18.0; P = .007) and the DbetaH 5'-Ins/Ins genotype (70.8 +/- 17.1; P = .02). CONCLUSIONS: This study found that patients with chronic schizophrenia had poorer cognitive function than the healthy controls in all examined cognitive domains except for visuospatial/constructional. No significant association was found between the DbetaH 5'-Ins/Del polymorphism and patients with chronic schizophrenia. However, the DbetaH 5'-Del/Del genotype may be specific to attentional decrements in patients with chronic schizophrenia. PMID- 26891014 TI - An improved cumulative sum-based procedure for prospective disease surveillance for count data in multiple regions. AB - We present an improved procedure for detecting outbreaks in multiple spatial regions using count data. We combine well-known methods for disease surveillance with recent developments from other areas to provide a more powerful procedure that is still relatively simple and fast to implement. Disease counts from neighboring regions are aggregated to compute a Poisson cumulative sum statistic for each region of interest. Instead of controlling the average run length criterion in the monitoring process, we instead utilize the FDR, which is more appropriate in a public health context. Additionally, p-values are used to make decisions instead of traditional critical values. The use of the FDR and p-values in testing allows us to utilize recently developed multiple testing methodologies, greatly increasing the power of this procedure. This is verified using a simulation experiment. The simplicity and rapid detection ability of this procedure make it useful in disease surveillance settings. The procedure is successfully applied in detecting the 2011 Salmonella Newport outbreak in 16 German federal states. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891015 TI - Prevention of Youthful Marijuana Use. AB - Considerable money and effort have been expended in attempts to prevent drug use by youth, with disappointing results. Too often, prevention programs have singled out youth with simplistic messages of exaggerated risk and the same politically acceptable solution for all-abstinence. Historically, prevention efforts have been less effective by not being soundly based in science and failing also to address adult drug and alcohol use as part of the problem. The Institute of Medicine continuum of care model developed in 1994 offers a framework for a more sophisticated, three-tiered approach to prevention, defined as all services provided prior to a clinical diagnosis of a substance use disorder. By dividing prevention efforts into universal (delivered to broad populations without consideration of individual risk for developing substance use disorder), selected (targeting sub-groups of individuals identified on the basis of characteristics known to create an elevated risk for substance use disorder), and indicated (addressing individuals identified on the basis of manifest risk behaviors), prevention can be better tailored to meet different levels of need. Student Assistance Programs (SAPs) and community coalitions provide examples of how IOM's continuum of care model can be integrated into drug prevention programs for youth. PMID- 26891016 TI - Ultrafast Killing and Self-Gelling Antimicrobial Imidazolium Oligomers. AB - Infectious diseases and the increasing threat of worldwide pandemics have underscored the importance of antibiotics and hygiene. Intensive efforts have been devoted to developing new antibiotics to meet the rapidly growing demand. In particular, advancing the knowledge of the structure-property-activity relationship is critical to expedite the design and development of novel antimicrobial with the needed potential and efficacy. Herein, a series of new antimicrobial imidazolium oligomers are developed with the rational manipulation of terminal group's hydrophobicity. These materials exhibit superior activity, excellent selectivity, ultrafast killing (>99.7% killing within 30 s), and desirable self-gelling properties. Molecular dynamic simulations reveal the delicate effect of structural changes on the translocation motion across the microbial cell membrane. The energy barrier of the translocation process analyzed by free energy calculations provides clear kinetic information to suggest that the spontaneous penetration requires a very short timescale of seconds to minutes for the new imidazolium oligomers. PMID- 26891017 TI - Language-general biases and language-specific experience contribute to phonological detail in toddlers' word representations. AB - Although toddlers in their 2nd year of life generally have phonologically detailed representations of words, a consistent lack of sensitivity to certain kinds of phonological changes has been reported. The origin of these insensitivities is poorly understood, and uncovering their cause is crucial for obtaining a complete picture of early phonological development. The present study explored the origins of the insensitivity to the change from coronal to labial consonants. In cross-linguistic research, we assessed to what extent this insensitivity is language-specific (or would show both in learners of Dutch and a very different language like Japanese), and contrast/direction-specific to the coronal-to-labial change (or would also extend to the coronal-to-dorsal change). We measured Dutch and Japanese 18-month-old toddlers' sensitivity to labial and dorsal mispronunciations of newly learned coronal-initial words. Both Dutch and Japanese toddlers showed reduced sensitivity to the coronal-to-labial change, although this effect was more pronounced in Dutch toddlers. The lack of sensitivity was also specific to the coronal-to-labial change because toddlers from both language backgrounds were highly sensitive to dorsal mispronunciations. Combined with results from previous studies, the present outcomes are most consistent with an early, language-general bias specific to the coronal-to-labial change, which is modified by the properties of toddlers' early, language-specific lexicon. PMID- 26891018 TI - Social and physical aggression trajectories from childhood through late adolescence: Predictors of psychosocial maladjustment at age 18. AB - This research examined whether following social and physical aggression trajectories across Grades 3-12 predicted psychological maladjustment. Teachers rated participants' (n = 287, 138 boys) aggressive behavior at the end of each school year. Following the 12th grade, psychosocial outcomes were measured: rule breaking behaviors, internalizing symptoms, and narcissistic and borderline personality features. Following the highest social aggression trajectory predicted rule-breaking behavior; the medium social aggression trajectory was not a significant predictor of any outcome. Following the highest physical aggression trajectory predicted rule-breaking, internalizing symptoms, and narcissism, whereas the medium physical aggression trajectory predicted rule-breaking and internalizing symptoms. PMID- 26891019 TI - Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy. AB - Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 ug/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. PMID- 26891021 TI - Cancer's Moonshot. PMID- 26891020 TI - A galectin-specific signature in the gut delineates Crohn's disease and ulcerative colitis from other human inflammatory intestinal disorders. AB - Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn's disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for beta-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosal-associated galectins (Gal-1, -3, -4, -9) is dysregulated in inflamed tissues of IBD patients compared with non-inflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker. PMID- 26891022 TI - Diagnostic value of echocardiography in isolated congenital unilateral lung agenesis combined with different anomalies: Two rare cases in children. AB - Unilateral lung agenesis, a rare congenital deformity, is secondary to abnormal embryonic development, leading to a shift of the mediastinum and remaining lung. In our case reports, we describe the diagnostic courses of two pediatric patients with unilateral lung agenesis admitted to our hospital in 2014. We present and compare the findings in transthoracic echocardiography with that in CT. Echocardiography played a pivotal role in revealing pulmonary deformities and leading to the diagnosis. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:514-517, 2016. PMID- 26891023 TI - Nonalcoholic fatty liver disease and elastography: Incremental advances but work still to be done. PMID- 26891024 TI - Medical Tourism for CCSVI Procedures in People with Multiple Sclerosis: An Observational Study. AB - BACKGROUND: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non-evidence-based medical tourism for CCSVI procedures. METHODS: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. RESULTS: In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. CONCLUSIONS: Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized. PMID- 26891026 TI - Directed self-assembly of solvent-vapor-induced non-bulk block copolymer morphologies on nanopatterned substrates. AB - We report a study on directed self-assembly (DSA) with solvent annealing to induce the formation of non-bulk block copolymer microdomains on chemical patterns. Ultrathin films of symmetric polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) display morphologies of PMMA dots, stripes, and PS hexagons with increasing exposure time to acetone vapor, a PMMA-selective solvent. All three nanostructures form long-range-ordered and registered arrays on striped chemical patterns with periods (LS) commensurate to the solvated PS-b PMMA microdomain period (L0,s). Solvent annealing is shown to facilitate DSA on non-regular chemical patterns, on which the local periods are incommensurate to L0,s. DSA with feature density multiplication, via solvent annealing, is also demonstrated. PMID- 26891025 TI - BVES Regulates Intestinal Stem Cell Programs and Intestinal Crypt Viability after Radiation. AB - Blood vessel epicardial substance (BVES/Popdc1) is a junctional-associated transmembrane protein that is underexpressed in a number of malignancies and regulates epithelial-to-mesenchymal transition. We previously identified a role for BVES in regulation of the Wnt pathway, a modulator of intestinal stem cell programs, but its role in small intestinal (SI) biology remains unexplored. We hypothesized that BVES influences intestinal stem cell programs and is critical to SI homeostasis after radiation injury. At baseline, Bves(-/-) mice demonstrated increased crypt height, as well as elevated proliferation and expression of the stem cell marker Lgr5 compared to wild-type (WT) mice. Intercross with Lgr5-EGFP reporter mice confirmed expansion of the stem cell compartment in Bves(-/-) mice. To examine stem cell function after BVES deletion, we used ex vivo 3D-enteroid cultures. Bves(-/-) enteroids demonstrated increased stemness compared to WT, when examining parameters such as plating efficiency, stem spheroid formation, and retention of peripheral cystic structures. Furthermore, we observed increased proliferation, expression of crypt-base columnar "CBC" and "+4" stem cell markers, amplified Wnt signaling, and responsiveness to Wnt activation in the Bves(-/-) enteroids. Bves expression was downregulated after radiation in WT mice. Moreover, after radiation, Bves(-/-) mice demonstrated significantly greater SI crypt viability, proliferation, and amplified Wnt signaling in comparison to WT mice. Bves(-/-) mice also demonstrated elevations in Lgr5 and Ascl2 expression, and putative damage responsive stem cell populations marked by Bmi1 and TERT. Therefore, BVES is a key regulator of intestinal stem cell programs and mucosal homeostasis. Stem Cells 2016;34:1626-1636. PMID- 26891029 TI - Catalytic formal cycloadditions between anhydrides and ketones: excellent enantio and diastereocontrol, controllable decarboxylation and the formation of adjacent quaternary stereocentres. AB - It has been shown for the first time that enolisable anhydrides can participate in highly efficient and diastereo/enantioselective additions to activated ketones. In these reactions the anhydride component formally acts (initially) as the nucleophilic component. These processes are promoted by novel, readily prepared urea-substituted cinchona alkaloid-derived catalysts at low loadings under mild conditions. Three classes of enolisable anhydride and three different types of activated ketone were shown to be compatible with the process - generating a diverse range of structurally distinct and densely functionalised lactone products with the formation of two new stereocentres, one of which is quaternary. In one example, a product incorporating two contiguous quaternary stereocentres (one all carbon) was formed with outstanding enantiocontrol. It has been shown in the case of glutaconic anhydride derivatives that the cycloaddtion process is reversible, and can be accompanied by decarboxylation and olefin isomerisation. Reaction conditions can be modified to give access to three types of product with good-excellent ee. PMID- 26891028 TI - Candida haemulonii Complex Species, Brazil, January 2010-March 2015. PMID- 26891027 TI - The dynamic AMPA receptor extracellular region: a platform for synaptic protein interactions. AB - AMPA receptors (AMPARs) are glutamate-gated cation channels that mediate fast excitatory neurotransmission and synaptic plasticity. Structures of GluA2 homotetramers in distinct functional states, together with simulations, emphasise the loose architecture of the AMPAR extracellular region (ECR). The ECR encompasses ~80% of the receptor, and consists of the membrane-distal N-terminal domain (NTD) and ligand-binding domain (LBD), which is fused to the ion channel domain. Minimal contacts within and between layers, together with flexible peptide linkers connecting these three domains give rise to an organisation capable of dynamic rearrangements. This building plan is uniquely suited to engage interaction partners in the crowded environment of synapses, permitting the formation of new binding sites and the loss of existing ones. ECR motions are thereby expected to impact signalling as well as synaptic anchorage and may thereby influence AMPAR clustering during synaptic plasticity. PMID- 26891030 TI - Motorcycle fuel tanks and pelvic fractures: A motorcycle fuel tank syndrome. AB - OBJECTIVE: Pelvic injuries are a serious and commonly occurring injury to motorcycle riders involved in crashes, yet there has been limited research investigating the mechanisms involved in these injuries. This study aimed to investigate the mechanisms involved in pelvic injuries to crashed motorcyclists. METHOD: This study involved in-depth crash investigation and 2 convenience-based data sets were used. These data sets investigated motorcycle crashes in the Sydney, Newcastle, and Adelaide regions. Participants included motorcycle riders who had crashed either on a public road or private property within the study areas. The mechanism of injury and the type of injuries were investigated. RESULTS: The most frequent cause of pelvic injuries in crashed motorcyclists was due to contact with the motorcycle fuel tank during the crash (85%). For riders who had come into contact with the fuel tank, the injury types were able to be grouped into 3 categories based on the complexity of the injury. The complexity of the injury appeared to increase with impact speed but this was a nonsignificant trend. The pelvic injuries that did not occur from contact with the fuel tank in this sample differed in asymmetry of loading and did not commonly involve injury to the bladder. They were commonly one-sided injuries but this differed based on the point of loading; however, a larger sample of these injuries needs to be investigated. CONCLUSION: Overall improvements in road safety have not been replicated in the amelioration of pelvic injuries in motorcyclists and improvements in the design of crashworthy motorcycle fuel tanks appear to be required. PMID- 26891031 TI - Tracking Cells in GFP-transgenic Zebrafish Using the Photoconvertible PSmOrange System. AB - The rapid development of transparent zebrafish embryos (Danio rerio) in combination with fluorescent labelings of cells and tissues allows visualizing developmental processes as they happen in the living animal. Cells of interest can be labeled by using a tissue specific promoter to drive the expression of a fluorescent protein (FP) for the generation of transgenic lines. Using fluorescent photoconvertible proteins for this purpose additionally allows to precisely follow defined structures within the expression domain. Illuminating the protein in the region of interest, changes its emission spectrum and highlights a particular cell or cell cluster leaving other transgenic cells in their original color. A major limitation is the lack of known promoters for a large number of tissues in the zebrafish. Conversely, gene- and enhancer trap screens have generated enormous transgenic resources discretely labeling literally all embryonic structures mostly with GFP or to a lesser extend red or yellow FPs. An approach to follow defined structures in such transgenic backgrounds would be to additionally introduce a ubiquitous photoconvertible protein, which could be converted in the cell(s) of interest. However, the photoconvertible proteins available involve a green and/or less frequently a red emission state and can therefore often not be used to track cells in the FP background of existing transgenic lines. To circumvent this problem, we have established the PSmOrange system for the zebrafish. Simple microinjection of synthetic mRNA encoding a nuclear form of this protein labels all cell nuclei with orange/red fluorescence. Upon targeted photoconversion of the protein, it switches its emission spectrum to far red. The quantum efficiency and stability of the protein makes PSmOrange a superb cell-tracking tool for zebrafish and possibly other teleost species. PMID- 26891032 TI - Laboratory Scale X-ray Fluorescence Tomography: Instrument Characterization and Application in Earth and Environmental Science. AB - A new laboratory scale X-ray fluorescence (XRF) imaging instrument, based on an X ray microfocus tube equipped with a monocapillary optic, has been developed to perform XRF computed tomography experiments with both higher spatial resolution (20 MUm) and a better energy resolution (130 eV @Mn-K(alpha)) than has been achieved up-to-now. This instrument opens a new range of possible applications for XRF-CT. Next to the analytical characterization of the setup by using well defined model/reference samples, demonstrating its capabilities for tomographic imaging, the XRF-CT microprobe has been used to image the interior of an ecotoxicological model organism, Americamysis bahia. This had been exposed to elevated metal (Cu and Ni) concentrations. The technique allowed the visualization of the accumulation sites of copper, clearly indicating the affected organs, i.e. either the gastric system or the hepatopancreas. As another illustrative application, the scanner has been employed to investigate goethite spherules from the Cretaceous-Paleogene boundary, revealing the internal elemental distribution of these valuable distal ejecta layer particles. PMID- 26891036 TI - Does first-line antiretroviral regimen impact risk for chronic kidney disease whatever the risk group? AB - OBJECTIVES: We used the D:A:D risk score for chronic kidney disease (CKD) for patients starting antiretroviral therapy (ART) in the recent years, and investigated whether specific regimens enhanced the risk of CKD in the different risk groups. DESIGN: Retrospective analysis of a prospectively collected cohort of French HIV-infected patients. METHODS: Patients who started their first ART after January the 1st, 2004 with a baseline estimated glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were analyzed. CKD was defined by confirmed eGFR less than 60 ml/min per 1.73 m. Incidence of CKD was estimated by Kaplan-Meier method, and Poisson regression models were used to quantify the relationship between CKD, exposure to the initial ART regimens and the D:A:D score. RESULTS: We included 6301 patients representing 21 936 person-years of follow-up (PYFU), median eGFR at baseline was 101 ml/min per 1.73 m (inter quartile range 86; 118) and CKD incidence 9.6/1000 PYFU. Five years probabilities of CKD were 0.65, 4.6 and 15.9% in the low, medium and high-risk groups, respectively. In patients treated with a boosted protease inhibitor, incidences rates were 7.1/1000 and 9.0/1000 PYFU in the absence or presence of tenofovir, respectively, and markedly increased with increasing risk score. In the low-risk group the treatment choice had no impact on CKD incidence. CONCLUSION: When choosing the ideal first antiretroviral regimen for one given patient, clinicians should rely on the D:A:D score and avoid some drugs in high-risk patients, whereas in low-risk patients classic regimens may be safely prescribed, with an economic benefit due to soon available generic formulations. PMID- 26891035 TI - Association of increased CD8+ and persisting C-reactive protein levels with restenosis in HIV patients after coronary stenting. AB - OBJECTIVES: The life expectancy of HIV-infected patients has recently been increasing. Although the mortality and morbidity associated with AIDS is decreasing, those associated with cardiovascular diseases and percutaneous coronary intervention (PCI) are receiving greater attention. Only limited data regarding coronary restenosis are available in these patients. DESIGN: In this prospective, systematic angiographic follow-up study, we enrolled HIV patients who underwent PCI for de-novo lesions and subsequent routine angiographic follow up for 6-8 months. Angiographic restenosis was defined as stenosis of at least 50% of the in-segment area. METHODS: Univariate and multivariate analyses were performed to evaluate restenosis and its predictors. RESULTS: Between May 2002 and March 2014, 47 patients with HIV underwent PCI in two high-volume centers in Munich, Germany. Of these patients, 41 with 131 de-novo lesions underwent invasive surveillance. One-quarter of the lesions treated subsequently presented with restenosis. Univariate analysis indicated that CD8 T-cell levels (P = 0.006), serum cholesterol (P = 0.042) and low-density lipoprotein-cholesterol (P = 0.042) levels at baseline, total number of stents (P = 0.047), and C-reactive protein level (P = 0.001) at follow-up were associated with restenosis. Multivariate analysis indicated that CD8 T-cell levels (P = 0.006) and persistent C-reactive protein elevation at 6-month follow-up (P = 0.00013) were independent predictors of restenosis. CONCLUSION: Inflammation, represented by CD8 T-cell levels, and persistent C-reactive protein elevation are independent predictors of angiographic restenosis and should therefore be closely monitored in HIV patients undergoing PCI. PMID- 26891033 TI - Epigenome-wide profiling of DNA methylation in paired samples of adipose tissue and blood. AB - Many epigenetic association studies have attempted to identify DNA methylation markers in blood that are able to mirror those in target tissues. Although some have suggested potential utility of surrogate epigenetic markers in blood, few studies have collected data to directly compare DNA methylation across tissues from the same individuals. Here, epigenomic data were collected from adipose tissue and blood in 143 subjects using Illumina HumanMethylation450 BeadChip array. The top axis of epigenome-wide variation differentiates adipose tissue from blood, which is confirmed internally using cross-validation and externally with independent data from the two tissues. We identified 1,285 discordant genes and 1,961 concordant genes between blood and adipose tissue. RNA expression data of the two classes of genes show consistent patterns with those observed in DNA methylation. The discordant genes are enriched in biological functions related to immune response, leukocyte activation or differentiation, and blood coagulation. We distinguish the CpG-specific correlation from the within-subject correlation and emphasize that the magnitude of within-subject correlation does not guarantee the utility of surrogate epigenetic markers. The study reinforces the critical role of DNA methylation in regulating gene expression and cellular phenotypes across tissues, and highlights the caveats of using methylation markers in blood to mirror the corresponding profile in the target tissue. PMID- 26891037 TI - Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AB - OBJECTIVE: The protein kinase C (PKC) agonist bryostatin-1 has shown significant ex-vivo potency to revert HIV-1 latency, compared with other latency reversing agents (LRA). The safety of this candidate LRA remains to be proven in treated HIV-1-infected patients. METHODS: In this pilot, double-blind phase I clinical trial (NCT 02269605), we included aviraemic HIV-1-infected patients on triple antiretroviral therapy to evaluate the effects of two different single doses of bryostatin-1 (10 or 20 MUg/m) compared with placebo. RESULTS: Twelve patients were included, four in each arm. Bryostatin-1 was well tolerated in all participants. Two patients in the 20 MUg/m arm developed grade 1 headache and myalgia. No detectable increases of cell-associated unspliced (CA-US) HIV-1-RNA were observed in any study arm, nor differences in HIV-1 mRNA dynamics between arms (P = 0.44). The frequency of samples with low-level viraemia did not differ between arms and low-level viraemia did not correlate with CA-US HIV-1-RNA levels (P = 0.676). No changes were detected on protein kinase C (PKC) activity and in biomarkers of inflammation (sCD14 and interleukin-6) in any study arm. After the single dose of bryostatin-1, plasma concentrations were under detection limits in all the patients in the 10 MUg/m arm, and below 50 pg/ml (0.05 nmol/l) in those in the 20 MUg/m arm. CONCLUSION: Bryostatin-1 was safe at the single doses administered. However, the drug did not show any effect on PKC activity or on the transcription of latent HIV, probably due to low plasma concentrations. This study will inform next trials aimed at assessing higher doses, multiple dosing schedules or combination studies with synergistic drugs. PMID- 26891034 TI - Identification of sirtuin 1 as a promising therapeutic target for hypertrophic scars. AB - BACKGROUND AND PURPOSE: Sirtuin1 (SIRT1), the founding member of mammalian class III histone deacetylases, is reported to be a drug target involved in fibrotic diseases. However, whether it is an effective drug target in hypertrophic scar treatment is still not known. EXPERIMENTAL APPROACH: In the present study, we observed that SIRT1 localized to both the epidermis and the dermis of skin tissues by immunohistochemistry. After knock-down of SIRT1 by shRNA or up regulating SIRT1 by resveratrol, the expression of alpha-SMA, Col1 and Col3 in fibroblasts were detected by western blots. A mouse excision wound healing model was used to observe the changes in collagen fibre associated with the different expression levels of SIRT1. KEY RESULTS: SIRT1 expression was inhibited in hypertrophic scar tissue. The down-regulation of SIRT1 resulted in an increased expression of alpha-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts. In contrast, the up-regulation of SIRT1 not only inhibited the expression of alpha-SMA, Col1 and Col3 in hypertrophic scar-derived fibroblasts but also blocked the activation of TGFbeta1-induced normal skin-derived fibroblasts. In the mouse model of wound healing, the deletion of SIRT1 resulted in denser collagen fibres and a more disordered structure, whereas resveratrol treatment led to a more organized and thinner collagen fibre, which was similar to that observed during normal wound healing. CONCLUSIONS AND IMPLICATIONS: The results revealed that SIRT1 negatively regulates TGFbeta1-induced fibroblast activation and inhibits excessive scar formation and is, therefore, a promising drug target for hypertrophic scar formation. PMID- 26891038 TI - Differences in expression of gut-homing receptors on CD4+ T cells in black and white HIV-negative men who have sex with men. AB - HIV incidence rates are higher among black men who have sex with men (BMSM) as compared with MSM of other race/ethnicities in the USA. We found that blood memory CD4 cells from BMSM express higher levels of alpha4beta7, the gut-homing integrin, compared with white MSM. Higher expression of alpha4beta7 on blood CD4 cells correlated with higher percentage of proliferating CD4alpha4beta7 cells in rectal tissue suggesting increased trafficking of potential HIV target cells to rectal mucosa could increase HIV susceptibility among BMSM. PMID- 26891039 TI - Alkaline Earth Metal Zirconate Perovskites MZrO3 (M=Ba(2+), Sr(2+), Ca(2+)) Derived from Molecular Precursors and Doped with Eu(3+) Ions. AB - The effect of alkaline earth metal alkoxides on the protonation of zirconocene dichloride was investigated. This approach enabled the design of compounds with preset molecular structures for generating high-purity binary metal oxide perovskites MZrO3 (M=Ba(2+), Sr(2+), Ca(2+)). Single-source molecular precursors [Ba4 Zr2 (MU6 -O)(MU3 ,eta(2)-OR)8 (OR)2(eta(2) -HOR)2 (HOR)2 Cl4], [Sr4 Zr2 (MU6 -O)(MU3 ,eta(2)-OR)8 (OR)2 (HOR)4 Cl4], [Ca4 Zr2 (MU6-O)(MU3 ,eta(2)-OR)8 (OR)2 Cl4], and [Ca6 Zr2 (MU2 ,eta(2)-OR)12 (MU-Cl)2 (eta(2) -HOR)4 Cl6 ]?8 CH2 Cl2 were prepared via elimination of the cyclopentadienyl ring from Cp2 ZrCl2 as CpH in the presence of M(OR)2 and alcohol ROH (ROH=CH3OCH2 CH2OH) as a source of protons. The resulting complexes were characterized by elemental analysis, IR and NMR spectroscopy, and single-crystal X-ray diffraction. The compounds were then thermally decomposed to MCl2 /MZrO3 mixtures. Leaching of MCl2 from the raw powder with deionized water produced highly pure perovskite-like oxide particles of 40-80 nm in size. Luminescence studies on Eu(3+)-doped MZrO3 revealed that the perovskites are attractive host lattices for potential applications in display technology. PMID- 26891040 TI - Brain levels of high-energy phosphate metabolites and executive function in geriatric depression. AB - OBJECTIVES: Depression in late life has been associated with difficulties in cognitive processing, particularly in the domains of executive function, processing speed and memory, and increases the risk of developing dementia suggesting a neurodegenerative phenotype. Mitochondrial dysfunction is frequently an early event in neurodegenerative illnesses and may be operative in patients with late life depression. Phosphorus magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules produced by mitochondria. METHODS: Ten patients with late life depression and eight normal elderly controls were studied with Stroop color and interference tests, which are widely used measures of processing speed and executive function, respectively, followed by (31P) MRS 3-dimensional chemical-shift imaging measuring levels of adenosine triphosphate, phosphocreatine, inorganic phosphate, and pH over the whole brain. RESULTS: In all subjects, gray matter phosphocreatine was positively associated with Stroop interference. Levels of white matter adenosine triphosphate were associated with Stroop interference in subjects with late life depression but not normal elderly. There was also a complementary association between white matter inorganic phosphate and Stroop interference in late life depression patients. CONCLUSIONS: These findings suggest two independent sources of executive function dependence on bioenergetic state in the aging brain. The dependence of executive function performance in subjects with late life depression on ATP in white matter may be associated with mitochondrial impairment and is consistent with predictions of the vascular depression hypothesis. Further research with wider neuropsychological testing targeting bioenergetic markers could help clarify the scope of these effects. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891048 TI - Tumor Heterogeneity Assessed by 18F-FDG PET/CT Is Not Significantly Associated with Nodal Metastasis in Breast Cancer Patients. AB - INTRODUCTION: The purpose of this study was to evaluate the association of tumor heterogeneity as assessed by positron emission tomography/computed tomography (PET/CT) with pathological factors of breast cancer, and the prediction of nodal metastasis through tumor heterogeneity. METHODS: From January 2013 to December 2013, 102 patients with invasive ductal carcinoma of the breast were enrolled into this study. [18F]Fluorodeoxyglucose PET/CT was performed before surgery. The metabolic tumor volume (MTV) of each lesion was calculated and a series of standardized uptake value (SUV) thresholds (e.g. 40%, 50%, 60%, 70%, and 80% of SUVmax) was obtained. A threshold-volume (dV/dT) curve was acquired by plotting thresholds to MTV values automatically calculated with these thresholds. Tumor heterogeneity was calculated from the slope of the threshold-volume curve and defined as heterogeneity factor (HF). RESULTS: HF differed significantly according to T stage (p < 0.0001), N stage (p = 0.0131) and American Joint Committee on Cancer (AJCC) stage (p = 0.0006). Among the pathological parameters, dermal lymphatic involvement (p = 0.0039) showed the significant correlations with HF. Lymphovascular invasion (p = 0.0005) was the only independent factor for predicting nodal metastasis. CONCLUSIONS: Tumor heterogeneity measured by 18F-FDG PET/CT is significantly associated with dermal lymphatic involvement. However, PET might not be able to predict nodal metastasis in breast cancer. PMID- 26891047 TI - Molecular Individual-Based Approach on Triatoma brasiliensis: Inferences on Triatomine Foci, Trypanosoma cruzi Natural Infection Prevalence, Parasite Diversity and Feeding Sources. AB - We used an individual-based molecular multisource approach to assess the epidemiological importance of Triatoma brasiliensis collected in distinct sites and ecotopes in Rio Grande do Norte State, Brazil. In the semi-arid zones of Brazil, this blood sucking bug is the most important vector of Trypanosoma cruzi- the parasite that causes Chagas disease. First, cytochrome b (cytb) and microsatellite markers were used for inferences on the genetic structure of five populations (108 bugs). Second, we determined the natural T. cruzi infection prevalence and parasite diversity in 126 bugs by amplifying a mini-exon gene from triatomine gut contents. Third, we identified the natural feeding sources of 60 T. brasiliensis by using the blood meal content via vertebrate cytb analysis. Demographic inferences based on cytb variation indicated expansion events in some sylvatic and domiciliary populations. Microsatellite results indicated gene flow between sylvatic and anthropic (domiciliary and peridomiciliary) populations, which threatens vector control efforts because sylvatic population are uncontrollable. A high natural T. cruzi infection prevalence (52-71%) and two parasite lineages were found for the sylvatic foci, in which 68% of bugs had fed on Kerodon rupestris (Rodentia: Caviidae), highlighting it as a potential reservoir. For peridomiciliary bugs, Galea spixii (Rodentia: Caviidae) was the main mammal feeding source, which may reinforce previous concerns about the potential of this animal to link the sylvatic and domiciliary T. cruzi cycles. PMID- 26891049 TI - Diverse Effects of a Seven-Year Experimental Grassland Fragmentation on Major Invertebrate Groups. AB - Habitat fragmentation is a major driver of biodiversity loss, but observed effects vary and may depend on the group examined. Time since fragmentation may explain some differences between taxonomical groups, as some species and thus species composition respond with a delay to changes in their environment. Impacts of drivers of global change may thus be underestimated in short-term studies. In our study we experimentally fragmented nutrient-poor dry calcareous grasslands and studied the response of species richness, individual density and species composition of various groups of invertebrates (gastropods, ants, ground beetles, rove beetles, orthoptera, spiders, woodlice) in 12 small (1.5 m * 1.5 m) and 12 large (4.5 m * 4.5 m) fragments and their corresponding control plots after 7 years. We further examined responses to fragmentation in relation to body size and habitat preferences. Responses to fragmentation varied between taxonomical groups. While spider species richness and individual density were lower in fragments, the opposite was true for an orthopteran species and woodlice. Species composition and beta-diversity differed between fragments and control plots for some groups. However, the interaction treatment*plot size was rarely significant. Species with high occupancy rates in undisturbed control plots responded more negatively to the fragmentation, while species with large body size were relatively more abundant in fragments in some groups. No effect of the fragmentation was found for ants, which may have the longest lag times because of long-lived colonies. However, relationships between abundance and the species' preferences for environmental factors affected by edge effects indicate that ant diversity too may be affected in the longer-term. Our results show the importance of considering different groups in conservation management in times of widespread fragmentation of landscapes. While species richness may respond slowly, changes in abundance related to habitat preferences or morphology may allow insights into likely long-term changes. PMID- 26891051 TI - Blood-Borne Markers of Fatigue in Competitive Athletes - Results from Simulated Training Camps. AB - Assessing current fatigue of athletes to fine-tune training prescriptions is a critical task in competitive sports. Blood-borne surrogate markers are widely used despite the scarcity of validation trials with representative subjects and interventions. Moreover, differences between training modes and disciplines (e.g. due to differences in eccentric force production or calorie turnover) have rarely been studied within a consistent design. Therefore, we investigated blood-borne fatigue markers during and after discipline-specific simulated training camps. A comprehensive panel of blood-born indicators was measured in 73 competitive athletes (28 cyclists, 22 team sports, 23 strength) at 3 time-points: after a run in resting phase (d 1), after a 6-day induction of fatigue (d 8) and following a subsequent 2-day recovery period (d 11). Venous blood samples were collected between 8 and 10 a.m. Courses of blood-borne indicators are considered as fatigue dependent if a significant deviation from baseline is present at day 8 (Deltafatigue) which significantly regresses towards baseline until day 11 (Deltarecovery). With cycling, a fatigue dependent course was observed for creatine kinase (CK; Deltafatigue 54+/-84 U/l; Deltarecovery -60+/-83 U/l), urea (Deltafatigue 11+/-9 mg/dl; Deltarecovery -10+/-10 mg/dl), free testosterone (Deltafatigue -1.3+/-2.1 pg/ml; Deltarecovery 0.8+/-1.5 pg/ml) and insulin linke growth factor 1 (IGF-1; Deltafatigue -56+/-28 ng/ml; Deltarecovery 53+/-29 ng/ml). For urea and IGF-1 95% confidence intervals for days 1 and 11 did not overlap with day 8. With strength and high-intensity interval training, respectively, fatigue-dependent courses and separated 95% confidence intervals were present for CK (strength: Deltafatigue 582+/-649 U/l; Deltarecovery -618+/ 419 U/l; HIIT: Deltafatigue 863+/-952 U/l; Deltarecovery -741+/-842 U/l) only. These results indicate that, within a comprehensive panel of blood-borne markers, changes in fatigue are most accurately reflected by urea and IGF-1 for cycling and by CK for strength training and team sport players. PMID- 26891052 TI - SeXX Matters in Infectious Disease Pathogenesis. PMID- 26891050 TI - Microparticle-Induced Activation of the Vascular Endothelium Requires Caveolin 1/Caveolae. AB - Microparticles (MPs) are small membrane fragments shed from normal as well as activated, apoptotic or injured cells. Emerging evidence implicates MPs as a causal and/or contributing factor in altering normal vascular cell phenotype through initiation of proinflammatory signal transduction events and paracrine delivery of proteins, mRNA and miRNA. However, little is known regarding the mechanism by which MPs influence these events. Caveolae are important membrane microdomains that function as centers of signal transduction and endocytosis. Here, we tested the concept that the MP-induced pro-inflammatory phenotype shift in endothelial cells (ECs) depends on caveolae. Consistent with previous reports, MP challenge activated ECs as evidenced by upregulation of intracellular adhesion molecule-1 (ICAM-1) expression. ICAM-1 upregulation was mediated by activation of NF-kappaB, Poly [ADP-ribose] polymerase 1 (PARP-1) and the epidermal growth factor receptor (EGFR). This response was absent in ECs lacking caveolin 1/caveolae. To test whether caveolae-mediated endocytosis, a dynamin-2 dependent process, is a feature of the proinflammatory response, EC's were pretreated with the dynamin-2 inhibitor dynasore. Similar to observations in cells lacking caveolin-1, inhibition of endocytosis significantly attenuated MPs effects including, EGFR phosphorylation, activation of NF-kappaB and upregulation of ICAM 1 expression. Thus, our results indicate that caveolae play a role in mediating the pro-inflammatory signaling pathways which lead to EC activation in response to MPs. PMID- 26891054 TI - The Difference in Prognosis between Renal Sinus Fat and Perinephric Fat Invasion for pT3a Renal Cell Carcinoma: A Meta-Analysis. AB - BACKGROUND: In the current Tumour-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both renal sinus fat invasion (SFI) and perinephric fat invasion (PFI) are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI) in a more comprehensive way, this meta-analysis was performed. METHODS: To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR) and/or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. RESULTS: A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS) (HR: 1.47, 95% CI: 1.19-1.83; P<0.001) compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21-3.12; P = 0.006). T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies. CONCLUSION: The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings. PMID- 26891055 TI - Short versus long gonadotropin-releasing hormone analogue suppression protocols in advanced age women undergoing IVF/ICSI. AB - OBJECTIVE: To compare the effective of two GnRH-a protocols for ovarian stimulation in advanced age women undergoing IVF/ICSI cycles. STUDY DESIGN: A total of 1149 IVF-ET/ICSI cycles were retrospectively identified. The cycles were divided two groups, namely a long-protocol group and a short-protocol group. RESULTS: The numbers of oocytes retrieved, and high-quality embryos in the long protocol group were significantly greater than those in the short-protocol group. In the long-protocol group, the implantation and pregnancy rates were 17.22% and 33.67%, respectively, and these values were significantly higher than those in the short-protocol group (8.24% and 15.96%, p < 0.05). CONCLUSIONS: Our study demonstrated that the long protocol was superior to the short protocol for advanced age women. PMID- 26891053 TI - Mortality Outcomes of Patients with Chronic Kidney Disease and Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with higher mortality in the general population. We studied the associations between COPD and death among chronic kidney disease (CKD) patients along with reporting cause-specific death data. METHODS: We included 56,960 patients with stages 3 and 4 CKD who were followed in a large health care system. Associations between COPD and all-cause mortality and various causes of death (respiratory deaths, cardiovascular deaths, malignancy-related deaths and deaths due to other reasons) were studied using the Cox proportional hazards and competing risk models. RESULTS: Out of 56,960 CKD patients, 4.7% (n = 2,667) had underlying COPD. Old age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, and smoking were associated with higher risk for COPD. During a median follow-up of 3.7 years, 15,969 patients died. After covariate adjustment, COPD was associated with a 41% increased risk (95% CI 1.31-1.52) for all-cause mortality, and fourfold increased risk (sub-hazard ratio 4.36, 95% CI 3.54-5.37) for respiratory-related deaths. In a sensitivity analysis that was performed by defining COPD as the use of relevant International Classification of Diseases-9 codes and medications used to treat COPD, similar results were noted. CONCLUSIONS: COPD is associated with higher risk for death among those with CKD, and an underlying lung disease accounts for significant proportion of deaths. These data highlight the need for further prospective studies to understand the underlying mechanisms and potential interventions to improve outcomes in this population. PMID- 26891057 TI - Phosphorylation promotes Al(iii) binding to proteins: GEGEGSGG as a case study. AB - Aluminum, the third most abundant element in the Earth's crust and one of the key industrial components of our everyday life, has been associated with several neurodegenerative diseases due to its ability to promote neurofilament tangles and beta-amyloid peptide aggregation. However, the experimental characterization of aluminum speciation in vivo is a difficult task. In the present study, we develop a theoretical protocol that combines molecular dynamics simulations, clustering of structures, and density functional theory for the characterization of the binding of aluminum to the synthetic neurofilament analogue octapeptide GEGEGSGG and its phosphorylated variant. Our protocol is tested with respect to previous NMR experimental data, which allows for a full interpretation of the experimental information available and its relationship with key thermodynamic quantities. Our results demonstrate the importance of phosphorylation in the ability of a peptide to bind to aluminum. Thus, phosphorylation: (i) changes the binding pattern of aluminum to GEGEGSGG, shifting the preferential binding site from the C-terminal to S6(P); (ii) increases the binding affinity by a factor of around 15 kcal mol(-1) in free energy; and (iii) may cause significant changes in the secondary structure and stiffness of the polypeptide chain, specially in the case of bidentate binding modes. Our results shed light on the possibility of aluminum to induce aggregation of beta-amyloid proteins and neurofilament tangles. PMID- 26891056 TI - Bovine Host Genetic Variation Influences Rumen Microbial Methane Production with Best Selection Criterion for Low Methane Emitting and Efficiently Feed Converting Hosts Based on Metagenomic Gene Abundance. AB - Methane produced by methanogenic archaea in ruminants contributes significantly to anthropogenic greenhouse gas emissions. The host genetic link controlling microbial methane production is unknown and appropriate genetic selection strategies are not developed. We used sire progeny group differences to estimate the host genetic influence on rumen microbial methane production in a factorial experiment consisting of crossbred breed types and diets. Rumen metagenomic profiling was undertaken to investigate links between microbial genes and methane emissions or feed conversion efficiency. Sire progeny groups differed significantly in their methane emissions measured in respiration chambers. Ranking of the sire progeny groups based on methane emissions or relative archaeal abundance was consistent overall and within diet, suggesting that archaeal abundance in ruminal digesta is under host genetic control and can be used to genetically select animals without measuring methane directly. In the metagenomic analysis of rumen contents, we identified 3970 microbial genes of which 20 and 49 genes were significantly associated with methane emissions and feed conversion efficiency respectively. These explained 81% and 86% of the respective variation and were clustered in distinct functional gene networks. Methanogenesis genes (e.g. mcrA and fmdB) were associated with methane emissions, whilst host-microbiome cross talk genes (e.g. TSTA3 and FucI) were associated with feed conversion efficiency. These results strengthen the idea that the host animal controls its own microbiota to a significant extent and open up the implementation of effective breeding strategies using rumen microbial gene abundance as a predictor for difficult-to-measure traits on a large number of hosts. Generally, the results provide a proof of principle to use the relative abundance of microbial genes in the gastrointestinal tract of different species to predict their influence on traits e.g. human metabolism, health and behaviour, as well as to understand the genetic link between host and microbiome. PMID- 26891059 TI - Tip-induced gating of molecular levels in carbene-based junctions. AB - We study the conductance of N-heterocyclic carbene-based (NHC) molecules on gold by means of first-principles calculations based on density-functional theory and non-equilibrium Green's functions. We consider several tip structures and find a strong dependence of the position of the NHC molecular levels with the atomistic structure of the tip. The position of the lowest unoccupied molecular orbital (LUMO) can change by almost 0.8 eV with tip shape. Through an analysis of the net charge transfer, electron redistribution and work function for each tip structure, we rationalize the LUMO shifts in terms of the sum of the work function and the maximum electrostatic potential arising from charge rearrangement. These differences in the LUMO position, effectively gating the molecular levels, result in large conductance variations. These findings open the way to modulating the conductance of NHC-based molecular circuits through the controlled design of the tip atomistic structure. PMID- 26891060 TI - Novel nervous system mechanisms in visceral pain. AB - Visceral hypersensitivity is an important factor underlying abdominal pain in functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and can result from aberrant signaling from the gut to the brain or vice versa. Over the last two decades, research has identified several selective, intertwining pathways that underlie IBS-related visceral nociception, including specific receptors on afferent and efferent nerve fibers such as transient receptor potential channels (TRP) channels, opioid, and cannabinoid receptors. In this issue of Neurogastroenterology and Motility Gil et al. demonstrate that in an animal model with reduced descending inhibitory control, the sympathetic nervous system outflow is enhanced, contributing to visceral and somatic hypersensitivity. They also provide evidence that interfering with the activation of adrenergic receptors on sensory nerves can be an interesting new strategy to treat visceral pain in IBS. This mini-review places these findings in a broader perspective by providing an overview of promising novel mechanisms to alter the nervous control of visceral pain interfering with afferent or efferent neuronal signaling. PMID- 26891062 TI - Antibiotic use and subsequent development of functional gastrointestinal disorders: effect of symptom-reporting and consultation behavior. PMID- 26891058 TI - Linking databases on perinatal health: a review of the literature and current practices in Europe. AB - BACKGROUND: International comparisons of perinatal health indicators are complicated by the heterogeneity of data sources on pregnancy, maternal and neonatal outcomes. Record linkage can extend the range of data items available and thus can improve the validity and quality of routine data. We sought to assess the extent to which data are linked routinely for perinatal health research and reporting. METHODS: We conducted a systematic review of the literature by searching PubMed for perinatal health studies from 2001 to 2011 based on linkage of routine data (data collected continuously at various time intervals). We also surveyed European health monitoring professionals about use of linkage for national perinatal health surveillance. RESULTS: 516 studies fit our inclusion criteria. Denmark, Finland, Norway and Sweden, the US and the UK contributed 76% of the publications; a further 29 countries contributed at least one publication. Most studies linked vital statistics, hospital records, medical birth registries and cohort data. Other sources were specific registers for: cancer (70), congenital anomalies (56), ART (19), census (19), health professionals (37), insurance (22) prescription (31), and level of education (18). Eighteen of 29 countries (62%) reported linking data for routine perinatal health monitoring. CONCLUSION: Research using linkage is concentrated in a few countries and is not widely practiced in Europe. Broader adoption of data linkage could yield substantial gains for perinatal health research and surveillance. PMID- 26891063 TI - Antibiotics and onset of functional gastrointestinal disorders. PMID- 26891061 TI - Objective prediction of pharyngeal swallow dysfunction in dysphagia through artificial neural network modeling. AB - BACKGROUND: Pharyngeal pressure-flow analysis (PFA) of high resolution impedance manometry (HRIM) with calculation of the swallow risk index (SRI) can quantify swallow dysfunction predisposing to aspiration. We explored the potential use of artificial neural networks (ANN) to model the relationship between PFA swallow metrics and aspiration and to predict swallow dysfunction. METHODS: Two hundred consecutive dysphagia patients referred for videofluoroscopy and HRIM were assessed. Presence of aspiration was scored and PFA software derived 13 metrics and the SRI. An ANN was created and optimized over training cycles to achieve optimal classification accuracy for matching inputs (PFA metrics) to output (presence of aspiration on videofluoroscopy). Application of the ANN returned a value between 0.00 and 1.00 reflecting the degree of swallow dysfunction. KEY RESULTS: Twenty one patients were excluded due to insufficient number of swallows (<4). Of 179, 58 aspirated and 27 had aspiration pneumonia history. The SRI was higher in aspirators (aspiration 24 [9, 41] vs no aspiration 7 [2, 18], p < 0.001) and patients with pneumonia (pneumonia 27 [5, 42] vs no pneumonia 8 [3, 24], p < 0.05). The ANN Predicted Risk was higher in aspirators (aspiration 0.57 [0.38, 0.82] vs no aspiration 0.13 [0.4, 0.25], p < 0.001) and in patients with pneumonia (pneumonia 0.46 [0.18, 0.60] vs no pneumonia 0.18 [0.6, 0.49], p < 0.01). Prognostic value of the ANN was superior to the SRI. CONCLUSIONS & INFERENCES: In a heterogeneous cohort of dysphagia patients, PFA with ANN modeling offers enhanced detection of clinically significant swallowing dysfunction, probably more accurately reflecting the complex interplay of swallow characteristics that causes aspiration. PMID- 26891064 TI - Risk of swallowing-related chest infections in patients with nasopharyngeal carcinoma treated with definitive intensity-modulated radiotherapy. AB - BACKGROUND: Pulmonary complications secondary to dysphagia may be encountered in patients with nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiotherapy. The purpose of this study was to identify patients with NPC at risk of developing swallowing-related chest infections (SRCIs). METHODS: Retrospective chart review was performed on 217 patients with stage I to IVB NPC treated definitively with radiotherapy or chemoradiotherapy. RESULTS: Twenty-six patients (12.0%) developed SRCIs; 4 of these patients (15.3%) required intensive care unit (ICU) admission and 9 (34.6%) died of the complication. The median time interval between completions of radiotherapy to the development of SRCIs was 24.5 months. Advanced age, recurrent disease, and concurrent chemoradiotherapy were significantly associated with the development of SRCIs in the multivariable analysis. CONCLUSION: SRCI is a common and potentially fatal complication for postirradiated patients with NPC. Advanced age, concurrent chemoradiotherapy, and recurrent cancer were strong risk factors for postirradiated patients with NPC to develop SRCIs. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1660-E1665, 2016. PMID- 26891065 TI - Geometrical deployment for braided stent. AB - The prediction of flow diverter stent (FDS) implantation for the treatment of intracranial aneurysms (IAs) is being increasingly required for hemodynamic simulations and procedural planning. In this paper, a deployment model was developed based on geometrical properties of braided stents. The proposed mathematical description is first applied on idealized toroidal vessels demonstrating the stent shortening in curved vessels. It is subsequently generalized to patient specific vasculature predicting the position of the filaments along with the length and local porosity of the stent. In parallel, in vitro and in-vivo FDS deployments were measured by contrast-enhanced cone beam CT (CBCT) in idealized and patient-specific geometries. These measurements showed a very good qualitative and quantitative agreement with the virtual deployments and provided experimental validations of the underlying geometrical assumptions. In particular, they highlighted the importance of the stent radius assessment in the accuracy of the deployment prediction. Thanks to its low computational cost, the proposed model is potentially implementable in clinical practice providing critical information for patient safety and treatment outcome assessment. PMID- 26891066 TI - Evaluation of state-of-the-art segmentation algorithms for left ventricle infarct from late Gadolinium enhancement MR images. AB - Studies have demonstrated the feasibility of late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging for guiding the management of patients with sequelae to myocardial infarction, such as ventricular tachycardia and heart failure. Clinical implementation of these developments necessitates a reproducible and reliable segmentation of the infarcted regions. It is challenging to compare new algorithms for infarct segmentation in the left ventricle (LV) with existing algorithms. Benchmarking datasets with evaluation strategies are much needed to facilitate comparison. This manuscript presents a benchmarking evaluation framework for future algorithms that segment infarct from LGE CMR of the LV. The image database consists of 30 LGE CMR images of both humans and pigs that were acquired from two separate imaging centres. A consensus ground truth was obtained for all data using maximum likelihood estimation. Six widely-used fixed-thresholding methods and five recently developed algorithms are tested on the benchmarking framework. Results demonstrate that the algorithms have better overlap with the consensus ground truth than most of the n-SD fixed thresholding methods, with the exception of the Full-Width-at-Half-Maximum (FWHM) fixed-thresholding method. Some of the pitfalls of fixed thresholding methods are demonstrated in this work. The benchmarking evaluation framework, which is a contribution of this work, can be used to test and benchmark future algorithms that detect and quantify infarct in LGE CMR images of the LV. The datasets, ground truth and evaluation code have been made publicly available through the website: https://www.cardiacatlas.org/web/guest/challenges. PMID- 26891067 TI - Vincristine Sulfate Liposomes Injection (VSLI, Marqibo(r)): Results From a Phase I Study in Children, Adolescents, and Young Adults With Refractory Solid Tumors or Leukemias. AB - BACKGROUND: Vincristine sulfate liposome injection (VSLI; Marqibo(r)) is an encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical trials in adults have demonstrated safety, tolerability, and activity, leading to Food and Drug Administration (FDA) approval for adults with relapsed acute lymphoblastic leukemia (ALL). Pediatric experience with VSLI is limited. PROCEDURE: This single center, phase I dose escalation study examined the safety, toxicity, maximum tolerated dose, and pharmacokinetics of VSLI administered weekly to pediatric patients age <21 years with relapsed or chemotherapy-refractory solid tumors or leukemia. RESULTS: Twenty-one subjects were treated in total. Median age was 13.3 years (range 2-19). Fourteen subjects completed one 28-day cycle of therapy and five subjects completed more than one cycle. No subject experienced dose-limiting toxicity (DLT) at the first dose level (1.75 mg/m(2) /dose, dose range: 2-3.7 mg). At the second dose level (2.25 mg/m(2) /dose, dose range: 1.3-4.5 mg), one subject had transient dose-limiting grade 4 transaminase elevation, and this dose level was expanded with no additional DLT observed. The second dose level then opened to an expansion phase to evaluate activity in ALL. Clinical activity included minimal residual disease negative complete remission in one subject with ALL and stable disease in nine subjects. Clearance of total vincristine was found to be approximately 100-fold lower in comparison to published data using standard vincristine. CONCLUSIONS: Children tolerate 2.25 mg/m(2) /dose of weekly VSLI (the adult FDA-approved dose) with evidence for clinical activity without dose-limiting neurotoxicity. Future plans include studying VSLI as substitution for standard vincristine with combination chemotherapy in children with ALL. PMID- 26891068 TI - Chronic lower back pain in a young adult. PMID- 26891071 TI - JTI Welcomes New Members to its Editorial Team. PMID- 26891069 TI - Modeling cytokinesis of eukaryotic cells driven by the actomyosin contractile ring. AB - A three-dimensional (3D) hydrodynamic model for cytokinesis of eukaryotic cells is developed, in which we model dynamics of actomyosins in the cell cortex, in particular, along the cytokinetic ring formed in the cortex and in the neighborhood of the cell's division plane explicitly. Specifically, the active force actuated by the actomyosin's activity along the cytokinetic ring is modeled by a surface force whose strength is proportional to the actomyosin concentration while the cell morphology is tracked by a phase field model. The model is then solved in 3D space and time using a finite difference method on graphic processing units. Dynamical morphological patterns of eukaryotic cells during cytokinesis are numerically simulated with the model. These simulated morphological patterns agree quantitatively with experimental observations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891072 TI - Imaging of Diffuse Lung Disease: An Ever-evolving Challenge. PMID- 26891070 TI - Simultaneous Dual Encoding of Three-Dimensional Structures by Light-Induced Modular Ligation. AB - A highly efficient strategy for the simultaneous dual surface encoding of 2D and 3D microscaffolds is reported. The combination of an oligo(ethylene glycol)-based network with two novel and readily synthesized monomers with photoreactive side chains yields two new photoresists, which can be used for the fabrication of microstructures (by two-photon polymerization) that exhibit a dual-photoreactive surface. By combining both functional photoresists into one scaffold, a dual functionalization pattern can be obtained by a single irradiation step in the presence of adequate reaction partners based on a self-sorting mechanism. The versatility of the approach is shown by the dual patterning of halogenated and fluorescent markers as well as proteins. Furthermore, we introduce a new ToF-SIMS mode ("delayed extraction") for the characterization of the obtained microstructures that combines high mass resolution with improved lateral resolution. PMID- 26891073 TI - Computed Tomographic Scoring Systems in Sarcoidosis: Comparison With Cardiopulmonary Exercise Testing Parameters. AB - PURPOSE: The aim of the study was to correlate computed tomographic (CT) scoring systems for pulmonary sarcoidosis with cardiopulmonary exercise testing and evaluate which scoring system provides the most reliable information for assessing disease severity and predicting impairment of gas exchange during exercise. MATERIALS AND METHODS: The institutional review board approved this retrospective study. All 62 patients underwent thin-section CT, pulmonary function tests, and cardiopulmonary exercise test. Two observers scored CT images according to scoring systems published by Remy-Jardin and colleagues. Spearman rank correlation coefficients were calculated between CT patterns and pulmonary functional impairment parameters, and multiple regression analyses were performed to evaluate which CT abnormalities were significantly associated with pulmonary functional impairment parameters. RESULTS: Regardless of scoring system, PaO2max was significantly associated with the subscores of ground-glass opacity, linear opacity, and total CT scores. Multiple regression analyses showed that subscores of ground-glass and linear opacity in the Leung scoring system appeared to explain a significant amount of variance in functional parameters at rest and at maximal exercise. CONCLUSIONS: CT findings, particularly ground-glass opacity and linear abnormalities, can explain a significant amount of variance in cardiopulmonary exercise parameters. This suggests that CT-based scoring systems are valid measures of disease severity in sarcoidosis. PMID- 26891074 TI - ACR Appropriateness Criteria(r) Routine Chest Radiography. AB - Chest radiographs are sometimes taken before surgeries and interventional procedures on hospital admissions and outpatients. This manuscript summarizes the American College of Radiology review of the literature and recommendations on routinely performed chest radiographies in these settings. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 26891075 TI - Economic evaluation on infant hepatitis B vaccination combined with immunoglobulin in China, 2013. PMID- 26891076 TI - Hypoxia/ischemia promotes CXCL10 expression in cardiac microvascular endothelial cells by NFkB activation. AB - CXCL10, the chemokine with potent chemotactic activity on immune cells and other non-immune cells expressing its receptor CXCR3, has been demonstrated to involve in myocardial infarction, which was resulted from hypoxia/ischemia. The cardiac microvascular endothelial cells (CMECs) are the first cell type which is implicated by hypoxia/ischemia. However, the potential molecular mechanism by which hypoxia/ischemia regulates the expression of CXCL10 in CMECs remains unclear. In the present study, the expression of CXCL10 was firstly examined by real-time PCR and ELISA analysis. Several potential binding sites (BS) for transcription factors including NF-kappaB (NFkB), HIF1 alpha (HIF1alpha) and FoxO3a were identified in the promoter region of CXCL10 gene from -2000 bp to -1 bp using bioinformatics software. Luciferase reporter gene vectors for CXCL10 promoter and for activation of above transcription factors were constructed. The activation of NFkB, hypoxia-inducible transcription factor-1 alpha (HIF-1alpha) and FoxO3a was also analyzed by Western blotting. It was shown that the production of CXCL10 in CMECs was significantly increased by hypoxia/ischemia treatment, in parallel with the activation of CXCL10 promoter examined by reporter gene vector system. Furthermore, transcription factors including NFkB, HIF1alpha and FoxO3a were activated by hypoxia/ischemia in CMECs. However, over expression of NFkB, but not that of HIF1alpha or FoxO3a, significantly promoted the activation of CXCL10 promoter reporter gene. These findings indicated that CXCL10 production in CMECs was significantly increased by hypoxia/ischemia, at least in part, through activation of NFkB pathway and subsequently binding to CXCL10 promoter, finally promoted the transcription of CXCL10 gene. PMID- 26891077 TI - Regio- and Stereoselective Cyanotriflation of Alkynes Using Aryl(cyano)iodonium Triflates. AB - A novel, mild, and versatile approach for regioselective syn-addition of both the CN and OTf groups of aryl(cyano)iodonium triflates to alkynes is described. The reaction uses Fe-catalysis and can be conducted in gram scale. Products of the vicinal cyanotriflation can be stereospecifically readily further functionalized, rendering the method highly valuable. PMID- 26891078 TI - History dependence of the electromyogram: Implications for isometric steady-state EMG parameters following a lengthening or shortening contraction. AB - Residual force enhancement (RFE) and force depression (FD) refer to an increased or decreased force following an active lengthening or shortening contraction, respectively, relative to the isometric force produced at the same activation level and muscle length. Our intent was to determine if EMG characteristics differed in the RFE or FD states compared with a purely isometric reference contraction for maximal and submaximal voluntary activation of the adductor pollicis muscle. Quantifying these alterations to EMG in history-dependent states allows for more accurate modeling approaches for movement control in the future. For maximal voluntary contractions (MVC), RFE was 6-15% (P<0.001) and FD was 12 19% (P<0.001). The median frequency of the EMG was not different between RFE, FD and isometric reference contractions for the 100% and 40% MVC intensities (P>0.05). However, root mean square EMG (EMGRMS) amplitude for the submaximal contractions was higher in the FD and lower in the RFE state, respectively (P<0.05). For maximal contractions, EMGRMS was lower for the FD state but was the same for the RFE state compared to the isometric reference contractions (P>0.05). Neuromuscular efficiency (NME; force/EMG) was lower in the force depressed state and higher in the force enhanced state (P<0.05) compared to the isometric reference contractions. EMG spectral properties were not altered between the force-enhanced and depressed states relative to the isometric reference contractions, while EMG amplitude measures were. PMID- 26891079 TI - Examination of ClpB Quaternary Structure and Linkage to Nucleotide Binding. AB - Escherichia coli caseinolytic peptidase B (ClpB) is a molecular chaperone with the unique ability to catalyze protein disaggregation in collaboration with the KJE system of chaperones. Like many AAA+ molecular motors, ClpB assembles into hexameric rings, and this reaction is thermodynamically linked to nucleotide binding. Here we show that ClpB exists in a dynamic equilibrium of monomers, dimers, tetramers, and hexamers in the presence of both limiting and excess ATPgammaS. We find that ClpB monomer is only able to bind one nucleotide, whereas all 12 sites in the hexameric ring are bound by nucleotide at saturating concentrations. Interestingly, dimers and tetramers exhibit stoichiometries of ~3 and 7, respectively, which is one fewer than the maximum number of binding sites in the formed oligomer. This observation suggests an open conformation for the intermediates based on the need for an adjacent monomer to fully form the binding pocket. We also report the protein-protein interaction constants for dimers, tetramers, and hexamers and their dependencies on nucleotide. These interaction constants make it possible to predict the concentration of hexamers present and able to bind to cochaperones and polypeptide substrates. Such information is essential for the interpretation of many in vitro studies. Finally, the strategies presented here are broadly applicable to a large number of AAA+ molecular motors that assemble upon nucleotide binding and interact with partner proteins. PMID- 26891080 TI - Sample Confirmation Testing: A Short Tandem Repeat-Based Quality Assurance and Quality Control Procedure for the eyeGENE Biorepository. AB - Quality assurance and quality control (QA/QC) procedures are vital to good biorepository management. The National Eye Institute (NEI) core CLIA-certified laboratory of the eyeGENE((r)) Network receives blood from individuals with inherited eye conditions and isolates DNA for clinical genetic diagnostic testing and research. Clinical genetic test results are returned to the affected individuals, making it imperative that sample integrity is preserved throughout laboratory processing. A clinically validated, short tandem repeat (STR)-based approach, termed Sample Confirmation Testing (SCT), was developed to ensure that no significant laboratory errors occurred during processing. SCT uses modified protocols from commercial kits to create and compare STR profiles for each participant's original blood and derived DNA. This QA/QC procedure has been performed on 47% of the more than 6000 participants in the eyeGENE Biorepository and has identified significant laboratory errors in 0.4% of samples tested. SCT improves the quality of the data returned to affected individuals and the data distributed to researchers using eyeGENE samples by ensuring the integrity of the samples and aiding in curation of the biorepository. This approach serves as a model for other repositories to improve sample quality and management procedures. PMID- 26891081 TI - Syndecan-4 Enhances Therapeutic Angiogenesis after Hind Limb Ischemia in Mice with Type 2 Diabetes. AB - Delivering syndecan-4 with FGF-2 improves the effectiveness of FGF-2 therapy for ischemia in the diabetic disease state. The syndecan-4 proteoliposomes significantly enhance in vitro tubule formation as well as blood perfusion and vessel density in the ischemic hind limbs of diseased ob/ob mice. Syndecan-4 therapy also induces a marked immunomodulation in the tissues, increasing the polarization of macrophages toward the M2 phenotype. PMID- 26891082 TI - Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. AB - OBJECTIVE: Neuromyelitis optica (NMO) and its spectrum disorders (NMOSD) are inflammatory demyelinating diseases (IDDs) with a specific biomarker, aquaporin-4 immunoglobulin G (AQP4-IgG). Prior NMO/NMOSD epidemiological studies have been limited by lack of AQP4-IgG seroprevalence assessment, absence of population based USA studies, and under-representation of blacks. To overcome these limitations, we sought to compare NMO/NMOSD seroepidemiology across 2 ethnically divergent populations. METHODS: We performed a population-based comparative study of the incidence (2003-2011) and prevalence (on December 31, 2011) of NMO/NMOSD and AQP4-IgG seroincidence and seroprevalence (sera collected in 80-84% of IDD cases) among patients with IDD diagnosis in Olmsted County, Minnesota (82% white [Caucasian]) and Martinique (90% black [Afro-Caribbean]). AQP4-IgG was measured by M1 isoform fluorescence-activated cell-sorting assays. RESULTS: The age- and sex-adjusted incidence (7.3 vs 0.7/1,000,000 person-years [p < 0.01]) and prevalence (10 vs 3.9/100,000 [p = 0.01]) in Martinique exceeded that in Olmsted County. The AQP4-IgG age- and sex-adjusted seroincidence (6.5 vs 0.7/1,000,000 person-years [p < 0.01]) and seroprevalence (7.9 vs 3.3/100,000 [p = 0.04]) were also higher in Martinique than Olmsted County. The ethnicity-specific prevalence was similar in Martinique and Olmsted County: 11.5 and 13/100,000 in blacks, and 6.1 and 4.0/100,000 in whites, respectively. NMO/NMOSD represented a higher proportion of IDD cases in Martinique than Olmsted County (16% vs 1.4%; p < 0.01). The onset age (median = 35-37 years) and female:male distribution (5-9:1) were similar across both populations; 60% of prevalent cases were either blind in 1 eye, dependent on a gait aid, or both. INTERPRETATION: This study reports the highest prevalence of NMO/NMOSD in any population (10/100,000 in Martinique), estimates it affects 16,000 to 17,000 in the USA (higher than previous predictions), and demonstrates it disproportionately affects blacks. Ann Neurol 2016;79:775-783. PMID- 26891083 TI - Mir-217 promotes inflammation and fibrosis in high glucose cultured rat glomerular mesangial cells via Sirt1/HIF-1alpha signaling pathway. AB - BACKGROUND: Silent information regulator 1 (Sirt1) plays a protective role in kidney. Sirt1 suppresses activation of hypoxia-inducible factor-1 alpha (HIF 1alpha), with MircroRNA-217 (Mir-217) being closely related to Sirt1. The relationship of Sirt1, HIF-1alpha and Mir-217, however, has never been reported in high glucose cultured rat glomerular mesangial cells (RMCs). Thus, we explored the role of Mir-217 on inflammation and fibrosis in RMCs cultured with high glucose in vitro through Sirt1/HIF-1alpha signaling pathway. METHODS: Rat glomerular mesangial cells were pre-incubated with Sirt1 activator Resveratrol prior to high glucose treatment. Furthermore the cells were transiently transfected with Sirt1 small interfering RNA (siRNA), HIF-1alpha siRNA and Mir 217 inhibitor using Lipofectamine 2000. Real-time PCR was used to analyse the expression of Mir-217, Sirt1 mRNA and HIF-1alpha mRNA; Western Blot was used to observe protein expression of Sirt1, HIF-1alpha, connective tissue growth factor, endothelin-1 and fibronectin; enzyme-linked immunosorbent assay was used to detect protein expression of transforming growth factor-beta1 and vascular endothelial growth factor. RESULTS: High glucose increased Mir-217 expression. High glucose decreased Sirt1 expression, accompanied by the increased HIF-1alpha expression and then promoted inflammation and fibrosis. In addition, Mir-217 gene silencing or Resveratrol could suppress the expression of HIF-1alpha, which in turn restrained inflammation and fibrosis in rat glomerular mesangial cells cultured with high glucose. CONCLUSION: This study clarified the role of Mir-217 in high glucose cultured rat glomerular mesangial cells through Sirt1/HIF-1alpha signaling pathway and provided new therapeutic targets for diabetic nephropathy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891085 TI - Studies of a photochromic model system using NMR with ex-situ and in-situ irradiation devices. AB - The switching behavior of a photochromic model system was investigated in detail via NMR spectroscopy in order to improve understanding of the compound itself and to provide ways to obtain insights into composition trends of a photo switchable (polymeric) material containing spiropyran/merocyanine units. In addition to the classical irradiation performed outside the magnet (ex-situ), a device for irradiation inside the NMR spectrometer (in-situ) was tested. Both setups are introduced, their advantages and disadvantages as well as their limits are described and the setup for future investigations of photochromic materials is suggested. The influence of different sample concentrations, irradiation procedures, and light intensities on the model system was examined as well as the dependence on solvent, temperature, and irradiation wavelengths. Using the recently published LED illumination device, it was even possible to record two dimensional spectra on this model system with rather short half-life (7 min in DMSO). This way (13) C chemical shifts of the merocyanine form were obtained, which were unknown before. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891087 TI - Implementing an electronic observation and early warning score chart in the emergency department: a feasibility study. AB - BACKGROUND: Use of automated systems to aid identification of patient deterioration in routine hospital practice is limited and their impact on patient outcomes remains unclear. This study was designed to evaluate the feasibility of implementing an electronic observation chart with automated early warning score (EWS) calculation in the high-acuity area of an emergency department. METHODS: This study enrolled 3219 participants before and 3352 after implementation of an automated system, using bedside vital-sign entry on networked mobile devices. The primary outcome measure was the percentage of participants for whom an EWS was accurately recorded at each stage. RESULTS: Of the participants, 52.7% before and 92.9% after implementation of the electronic system had an accurate EWS recorded on charts available to the study team. Participant groups were well balanced for baseline characteristics and acuity. CONCLUSION: In this study, the feasibility and limitations of implementing an electronic observation chart in the ED were demonstrated. Accurate EWS documentation was more frequent after implementation of the electronic observation chart. Retrospective analysis suggests that the use of an electronic observation system may lead to a greater percentage of observations being taken from those patients with a higher EWS. PMID- 26891084 TI - Antimicrobial blue light inactivation of Pseudomonas aeruginosa by photo excitation of endogenous porphyrins: In vitro and in vivo studies. AB - Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is responsible for about 10% of all hospital-acquired infections. In the present study, we investigated the potential development of tolerance of P. aeruginosa to antimicrobial blue light by carrying 10 successive cycles of sublethal blue light inactivation. The high-performance liquid chromatographic (HPLC) analysis was performed to identify endogenous porphyrins in P. aeruginosa cells. In addition, we tested the effectiveness of antimicrobial blue light in a mouse model of nonlethal skin abrasion infection by using a bioluminescent strain of P. aeruginosa. The results demonstrated that no tolerance was developed to antimicrobial blue light in P. aeruginosa after 10 cycles of sub-lethal inactivation. HPLC analysis showed that P. aeruginosa is capable of producing endogenous porphyrins in particularly, coproporphyrin III, which are assumed to be responsible for the photodynamic effects of blue light alone. P. aeruginosa infection was eradicated by antimicrobial blue light alone (48 J/cm(2) ) without any added photosensitizer molecules in the mouse model. In conclusion, endogenous photosensitization using blue light should gain considerable attention as an effective and safe alternative antimicrobial therapy for skin infections. Lasers Surg. Med. 48:562-568, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26891086 TI - Duplex ultrasound in the early diagnosis of acute mesenteric ischemia: a longitudinal cohort multicentric study. AB - OBJECTIVE: Acute mesenteric ischemia (AMI) is a life-threatening condition requiring time-dependent treatment; thus, early recognition may improve outcomes. We hypothesized that clinician-performed mesenteric vessels duplex ultrasound (DUS) could facilitate early identification of patients with AMI in high-risk patients presenting with abdominal pain. METHODS: This was a single-operator, observational, prospective cohort study. Patients aged at least 65 presenting to Emergency Departments with acute abdominal pain and no clear diagnosis after an initial work-up were enrolled. All patients underwent multidetector computed tomography and these findings provided the reference standard in this study. DUS of the celiac artery and superior mesenteric artery (SMA) were obtained to measure the peak systolic velocity (PSV) and were performed within 24 h of admission. PSVs outside the normal range were considered to indicate AMI. RESULTS: Of 49 patients identified, 47 were consented to enrollment and diagnostic images were obtained in 45 (96%). Fifteen patients (33%) had AMI (six occlusive, nine nonocclusive disease). Among these, 12 (80%) had abnormal DUS velocities. SMA PSV showed a sensitivity of 78.57% [95% confidence interval (CI): 49.2-95.34], a specificity of 64.52% (95% CI: 45.37-80.77), a positive predictive value of 50% (95% CI: 28.22-71.78), and a negative predictive value of 86.96% (95% CI: 66.41-97.22) for AMI. DUS had a sensitivity of 100%, a specificity of 64%, and a negative predictive value of 100% for occlusive AMI. Assessment of celiac artery PSV did not improve diagnostic performance. CONCLUSION: In this single-operator pilot study, mesenteric vessel DUS was performed successfully in the Emergency Department, with a high proportion of diagnostic images obtained. A normal SMA PSV was associated with a low risk of occlusive AMI. PMID- 26891088 TI - Light-up fluorophore--DNA aptamer pair for label-free turn-on aptamer sensors. AB - We developed a light-up fluorophore-DNA aptamer pair for label-free aptamer sensors that fluoresce upon binding to the analyte. A 42mer DNA aptamer binding to the environment-sensitive fluorophore, dapoxyl, which increased the fluorescence by more than 700-fold upon binding, was successfully used to construct aptamer sensors by fusion with analyte-binding DNA aptamers. PMID- 26891090 TI - Synthesis, Electrochemistry, and Excited-State Properties of Three Ru(II) Quaterpyridine Complexes. AB - The complexes [Ru(qpy)LL'](2+) (qpy = 2,2':6',2":6",2'''-quaterpyridine), with 1: L = acetonitrile, L'= chloride; 2: L = L'= acetonitrile; and 3: L = L'= vinylpyridine, have been prepared from [Ru(qpy) (Cl)2]. Their absorption spectra in CH3CN exhibit broad metal-to-ligand charge transfer (MLCT) absorptions arising from overlapping (1)A1 -> (1)MLCT transitions. Photoluminescence is not observed at room temperature, but all three are weakly emissive in 4:1 ethanol/methanol glasses at 77 K with broad, featureless emissions observed between 600 and 1000 nm consistent with MLCT phosphorescence. Cyclic voltammograms in CH3CN reveal the expected Ru(III/II) redox couples. In 0.1 M trifluoroacetic acid (TFA), 1 and 2 undergo aquation to give [Ru(II)(qpy)(OH2)2](2+), as evidenced by the appearance of waves for the couples [Ru(III)(qpy)(OH2)2](3+)/[Ru(II)(qpy)(OH2)2](2+), [Ru(IV)(qpy)(O)(OH2)](2+)/[Ru(III)(qpy)(OH2)2](3+), and [Ru(VI)(qpy)(O)2](2+)/[Ru(IV)(qpy)(O)(OH2)](2+) in cyclic voltammograms. PMID- 26891089 TI - Preliminary Favorable Outcome for Medically and Surgically Managed Extensively Drug-Resistant Tuberculosis, France, 2009-2014. AB - We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation. PMID- 26891093 TI - Anodized Steel Electrodes for Supercapacitors. AB - Steel was anodized in 10 M NaOH to enhance its surface texture and internal surface area for application as an electrode in supercapacitors. A mechanism was proposed for the anodization process. Field-emission gun scanning electron microscopy (FEGSEM) studies of anodized steel revealed that it contains a highly porous sponge like structure ideal for supercapacitor electrodes. X-ray photoelectron spectroscopy (XPS) measurements showed that the surface of the anodized steel was Fe2O3, whereas X-ray diffraction (XRD) measurements indicated that the bulk remained as metallic Fe. The supercapacitor performance of the anodized steel was tested in 1 M NaOH and a capacitance of 18 mF cm(-2) was obtained. Cyclic voltammetry measurements showed that there was a large psueudocapacitive contribution which was due to oxidation of Fe to Fe(OH)2 and then further oxidation to FeOOH, and the respective reduction of these species back to metallic Fe. These redox processes were found to be remarkably reversible as the electrode showed no loss in capacitance after 10000 cycles. The results demonstrate that anodization of steel is a suitable method to produce high surface-area electrodes for supercapacitors with excellent cycling lifetime. PMID- 26891092 TI - Highly Concentrated Ethanol Solutions: Good Solvents for DNA as Revealed by Single-Molecule Observation. AB - We observed single DNA molecules at different ethanol concentrations by using fluorescence microscopy. Large single DNA molecules undergo reentrant conformational transitions from elongated coil into folded globule and then into elongated coil state, accompanied by the increase of the concentration of ethanol in a low-salt aqueous environment. The second transition from globule into the coil state occurs at around 70 % (v/v) ethanol. From circular dichroism (CD) measurements, it is confirmed that the reentrant transition of the higher order structure proceeds together with the transitions of the secondary structure from B to C and, then, from C to A in a cooperative manner. The determined mechanism of the reentrant transition is discussed in relation to the unique characteristics of solutions with higher ethanol content, for which clathrate like nanostructures of alcohol molecules are generated in the surrounding water. PMID- 26891094 TI - Biologics and biosimilars: a legal perspective from Canada. PMID- 26891095 TI - A Hormone-responsive 3D Culture Model of the Human Mammary Gland Epithelium. AB - The process of mammary epithelial morphogenesis is influenced by hormones. The study of hormone action on the breast epithelium using 2D cultures is limited to cell proliferation and gene expression endpoints. However, in the organism, mammary morphogenesis occurs in a 3D environment. 3D culture systems help bridge the gap between monolayer cell culture (2D) and the complexity of the organism. Herein, we describe a 3D culture model of the human breast epithelium that is suitable to study hormone action. It uses the commercially available hormone responsive human breast epithelial cell line, T47D, and rat tail collagen type 1 as a matrix. This 3D culture model responds to the main mammotropic hormones: estradiol, progestins and prolactin. The influence of these hormones on epithelial morphogenesis can be observed after 1- or 2-week treatment according to the endpoint. The 3D cultures can be harvested for analysis of epithelial morphogenesis, cell proliferation and gene expression. PMID- 26891096 TI - Rigid Conjugated Twisted Truxene Dimers and Trimers as Electron Acceptors. AB - A new class of rigid twisted truxenone oligomers with an enlarged pi backbone has been established by oxidative dimerization reactions. The resulting extended conjugated systems have large extinction coefficients and low-lying LUMO levels and show good solubility in common organic solvents, thus making them attractive compounds as new electron acceptors in organic electronics. Their suitability as electron acceptors has been demonstrated in bulk-heterojunction organic solar cells with poly({4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6 diyl}{3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl}) (PTB7) as the donor material. PMID- 26891098 TI - Changing Hydrogen-Bond Structure during an Aqueous Liquid-Liquid Transition Investigated with Time-Resolved and Two-Dimensional Vibrational Spectroscopy. AB - We investigate the putative liquid-liquid phase transition in aqueous glycerol solution, using the OD-stretch mode in dilute OD/OH isotopic mixtures to probe the hydrogen-bond structure. The conversion exhibits Avrami kinetics with an exponent of n = 2.9 +/- 0.1 (as opposed to n = 1.7 observed upon inducing ice nucleation and growth in the same sample), which indicates a transition from one liquid phase to another. Two-dimensional infrared (2D-IR) spectroscopy shows that the initial and final phases have different hydrogen-bond structures: the former has a single Gaussian distribution of hydrogen-bond lengths, whereas the latter has a bimodal distribution consisting of a broad distribution and a narrower, ice like distribution. The 2D-IR spectrum of the final phase is identical to that of ice/glycerol at the same temperature. Combined with the kinetic data this suggests that the liquid-liquid transformation is immediately followed by a rapid formation of small (probably nanometer-sized) ice crystals. PMID- 26891097 TI - Decoding the chemokine network that links leukocytes with decidual cells and the trophoblast during early implantation. AB - Chemokine network is central to the innate and adaptive immunity and entails a variety of proteins and membrane receptors that control physiological processes such as wound healing, angiogenesis, embryo growth and development. During early pregnancy, the chemokine network coordinates not only the recruitment of different leukocyte populations to generate the maternal-placental interface, but also constitutes an additional checkpoint for tissue homeostasis maintenance. The normal switch from a pro-inflammatory to an anti-inflammatory predominant microenvironment characteristic of the post-implantation stage requires redundant immune tolerance circuits triggered by key master regulators. In this review we will focus on the recruitment and conditioning of maternal immune cells to the uterus at the early implantation period with special interest on high plasticity macrophages and dendritic cells and their ability to induce regulatory T cells. We will also point to putative immunomodulatory polypeptides involved in immune homeostasis maintenance at the maternal-placental interface. PMID- 26891099 TI - Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer. AB - The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-kappaB, AKT, and ERK signaling, P gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer. PMID- 26891101 TI - Will mouth wash solutions of water, salt, sodiumbicarbonate or citric acid improve upper gastrointestinal symptoms in chronic kidney disease. AB - BACKGROUND: Uraemic symptoms including taste changes, nausea and dry retching are common in chronic kidney disease (CKD). Taste buds detect five basic tastes: sweet, salty, sour, umami and bitter. Saliva in CKD usually has increased concentrations of urea, sodium, potassium, phosphate and higher pH levels. Genetic sensitivities to the bitter taste, with the changes in saliva can cause taste changes and impact uraemic symptoms. AIM: The aim of this study was to assess if mouth wash solutions of water, salt, sodium bicarbonate or citric acid improves upper gastrointestinal (GI) symptoms in CKD patients. METHODS: An interventional crossover study with 42 CKD patients (21 men, 21 women) complaining of upper GI symptoms were recruited. Subjects completed a questionnaire to assess symptoms and tested for genetic taste sensitivities. Saliva samples were analysed. Mouth rinse solutions of salt, bicarbonate, citric acid and de-ionised water were trialled in randomized order for patient reaction and symptom improvement. RESULTS: All 42 patients experienced anorexia, 39 (93%) reported taste changes, 27 (48%) nausea and 27 (48%) dry retching. All solutions improved symptoms in some patients. Sodium bicarbonate (P = 0.005) gave the greatest improvement in mouth feel and symptom control compared with the least favoured citric acid solution. Sixty-six percent of patients found sodium bicarbonate beneficial with 40% preference over other solutions. CONCLUSION: Simple mouthwashes can be used to relieve or eliminate some uraemic symptoms. Rinsing the mouth with a sodium bicarbonate solution cleanses receptors on taste buds and may alter mouth pH thereby reducing some upper GI symptoms that CKD patients can experience. PMID- 26891102 TI - [The Prevalence of Current Depressive Symptoms in an Urban Adult Population]. AB - Objective We sought to provide prevalence rates of depressive symptoms in the adult population of the city of Leipzig, Germany (18 - 79 years; N = 8,861). Methods Data were derived from the Leipzig population-based study of adults (LIFE ADULT-Study). The German version of the Center for Epidemiological Studies Depression Scale (CES-D) was used to assess depressive symptoms using a cut-off score >= 23 points. Results The prevalence of current depressive symptoms was 6.4 % (95 %-KI = 5.4 - 7.4). Significantly higher prevalence rates were found in females than in males, in individuals in middle age (40 - 59 years) than in younger and older adults as well as in those individuals with lower socioeconomic status (SES). Conclusion The study findings did not indicate a generally increased risk of depressive symptoms in urban-living adults. PMID- 26891103 TI - [Subjective Experiences of Ward Rules on Wards for Treatment of Alcohol Dependency]. AB - Objective To examine the understanding of and attitudes towards ward rules among patients and staff on 5 wards for treatment of alcohol addiction in 5 hospitals. 4 wards were specialized, one was a general psychiatric ward. Methods Development of a questionnaire, measurement of patient satisfaction (ZUF-8), ward atmosphere (SBB), and hospital admission experience (FEA-P). Results For 24 previously identified areas, patients (N = 134) and staff (N = 41) reported 18.7 rules on average. Contentment with rules was generally high without significant differences between patients and staff. On the general ward, fewer rules were reported than on the specialized wards. Patient satisfaction, ward atmosphere and hospital admission experience were similar between normal and specialized wards. Conclusions Ward rules are common and detailed, and are highly valued by staff and patients. Rules can be considered as an important element of treatment for patients with alcohol addiction. There was no evidence of a superiority of the disorder-specific wards. PMID- 26891104 TI - "APEC Blue": Secondary Aerosol Reductions from Emission Controls in Beijing. AB - China implemented strict emission control measures in Beijing and surrounding regions to ensure good air quality during the 2014 Asia-Pacific Economic Cooperation (APEC) summit. We conducted synchronous aerosol particle measurements with two aerosol mass spectrometers at different heights on a meteorological tower in urban Beijing to investigate the variations in particulate composition, sources and size distributions in response to emission controls. Our results show consistently large reductions in secondary inorganic aerosol (SIA) of 61-67% and 51-57%, and in secondary organic aerosol (SOA) of 55% and 37%, at 260 m and ground level, respectively, during the APEC summit. These changes were mainly caused by large reductions in accumulation mode particles and by suppression of the growth of SIA and SOA by a factor of 2-3, which led to blue sky days during APEC commonly referred to as "APEC Blue". We propose a conceptual framework for the evolution of primary and secondary species and highlight the importance of regional atmospheric transport in the formation of severe pollution episodes in Beijing. Our results indicate that reducing the precursors of secondary aerosol over regional scales is crucial and effective in suppressing the formation of secondary particulates and mitigating PM pollution. PMID- 26891105 TI - Long-Term use of Modified Diets in Huntington's Disease: A Descriptive Clinical Practice Analysis on Improving Dietary Enjoyment. AB - Dysphagia is a very common occurrence in Huntington's disease (HD). As such, many people with HD require texture modified diets. This commentary discusses the implications for individuals living long-term on modified diets, including the loss of sensory stimulation and dietary enjoyment. Clinical practice analyses of two interventions aimed at promoting dietary satisfaction and involvement in food preparation for those with HD are described and parameters for future research are discussed. PMID- 26891107 TI - Bowen's disease presenting as erythema of the lower lid. PMID- 26891108 TI - The clinical picture of Alzheimer's disease in the decade before diagnosis: clinical and biomarker trajectories. AB - OBJECTIVE: Increasing evidence suggests that Alzheimer's disease begins at least a decade before the diagnosis of dementia. Earlier identification of the disease will have important implications for intervention; however, current models of preclinical changes are theoretical and require verification from empirical observations. Furthermore, these models have not incorporated psychiatric features. METHOD: Clinical and biological markers were examined at baseline (1999 2001) in 9,076 people aged 65 years and older. A nested case-control study included 830 cases with Alzheimer's disease diagnosed by DSM-IV criteria during the 10-year follow-up and twice as many controls. By taking the distance between baseline and diagnosis as the length of the preclinical period, disease marker trajectories were estimated using nonparametric locally weighted smoothing analysis. RESULTS: Significant differences for the cases compared to the controls were observed on both intercept and slope for truncated amyloid beta40 (P = .006; P = .003, respectively), C-reactive protein (P = .03; P = .05), verbal fluency (P < .0001; P < .0001), visual recall (P < .0001; P = .007), and hippocampal volume (P = .0002; P = .04) and on the slope only for truncated amyloid beta42 (P = .01). The cases showed higher levels of depressive symptoms (P = .003), which remained stable over the 10 years to diagnosis. CONCLUSIONS: As hypothesized by existing theoretical models, changes in plasma amyloid beta levels, hippocampal atrophy, cognitive loss, and C-reactive protein are already observed up to 10 years before diagnosis. An acceleration in cognitive decline appears to follow a significant increase in amyloid accumulation, and depressive symptomatology remains at a constantly higher level. Overall, clinical and biological markers do not follow the same trajectories; the clinical picture changes according to distance from dementia. PMID- 26891109 TI - Score test for association between recurrent events and a terminal event. AB - The statistical analysis of recurrent events relies on the assumption of independent censoring. When random effects are used, this means, in addition, that the censoring cannot depend on the random effect. Whenever the recurrent event process is terminated by death, this assumption might not be satisfied. Because joint models arising from such situations are more difficult to fit and interpret, clinicians rarely check whether joint modeling is preferred. In this paper, we propose and compare simple, yet efficient methods for testing whether the terminal event and the recurrent events are associated or not. The performance of the proposed methods is evaluated in a simulation study, and the sensitivity to misspecification of the model is assessed. Finally, the methods are illustrated on a data set comprising repeated observations of skin tumors on T-cell lymphoma patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891100 TI - Future Research Directions in the Positive Valence Systems: Measurement, Development, and Implications for Youth Unipolar Depression. AB - The Positive Valence Systems (PVS) have been introduced by the National Institute of Mental Health as a domain to help organize multiple constructs focusing on reward-seeking behaviors. However, the initial working model for this domain is strongly influenced by adult constructs and measures. Thus, the present review focuses on extending the PVS into a developmental context. Specifically, the review provides some hypotheses about the structure of the PVS, how PVS components may change throughout development, how family history of depression may influence PVS development, and potential means of intervening on PVS function to reduce onsets of depression. Future research needs in each of these areas are highlighted. PMID- 26891106 TI - Huntington's Disease Protein Huntingtin Associates with its own mRNA. AB - BACKGROUND: The Huntington's disease (HD) protein huntingtin (Htt) plays a role in multiple cellular pathways. Deregulation of one or more of these pathways by the mutant Htt protein has been suggested to contribute to the disease pathogenesis. Our recent discovery-based proteomics studies have uncovered RNA binding proteins and translation factors associated with the endogenous Htt protein purified from mouse brains, suggesting a potential new role for Htt in RNA transport and translation. OBJECTIVE: To investigate how Htt might affect RNA metabolism we set out to purify and analyze RNA associated with Htt. METHODS: RNA was extracted from immunopurified Htt-containing protein complexes and analyzed by microarrays and RNA-Seq. RESULTS: Surprisingly, the most enriched mRNA that co purified with Htt was Htt mRNA itself. The association of Htt protein and Htt mRNA was detected independent of intact ribosomes suggesting that it is not an RNA undergoing translation. Furthermore, we identified the recently reported mis spliced Htt mRNA encoding a truncated protein comprised of exon 1 and a portion of the downstream intron in the immunoprecipitates containing mutant Htt protein. We show that Htt protein co-localizes with Htt mRNA and that wild-type Htt reduces expression of a reporter construct harboring the Htt 3' UTR. CONCLUSIONS: HD protein is found in a complex with its own mRNA and RNA binding proteins and translation factors. Htt may be involved in modulating its expression through post-transcriptional pathways. It is possible that Htt shares mechanistic properties similar to RNA binding proteins such as TDP-43 and FUS implicated in other neurodegenerative diseases. PMID- 26891111 TI - Are antidepressants effective? A debate on their efficacy for the treatment of major depression in adults. AB - Recently, the efficacy of antidepressants, a treatment used by 11% of US American adults, has been debated. Thousands of randomized controlled trials (RCTs) have been used to study antidepressants, with the majority demonstrating at least moderate superiority over placebo. In contrast, studies have found antidepressant effects to be unspecific and mainly resulting from placebo. The effects of antidepressants may also be overestimated due to selective publishing and selection of patients who have a high chance of response in RCTs. Studies have also shown the drugs do not reduce suicidal events when compared to placebo, and efficacy differences to placebo are often too small to prove clinical relevance. Here, we review the claims for and against antidepressant efficacy. PMID- 26891110 TI - Mitigation of Marijuana-Related Legal Harms to Youth in California. AB - If recreational marijuana is legalized for adults in California, a rational implementation of public policy would neither criminalize youth possession, nor medically pathologize it by conflating possession with addiction. The harms of a criminal justice approach to juveniles should not exceed the harms of the drug itself. Juvenile arrests and probation have consequences: (1) arrest records, probation, and juvenile hall; (2) an incarceration subculture, "crime school," psychological and re-entry costs; (3) school "zero-tolerance" expulsions and suspensions; (4) ineligibility for federal school loans; (5) employment screening problems; (6) racial disparities in arrests; (7) fines and attorney's fees; and (8) immigration/naturalization problems. Marijuana-related arrest rates in California dropped after a 2011 law making possession under 1 oz. an infraction for all, but juvenile marijuana arrests continue to outnumber arrests for hard drugs. Recommendations for prudent implementation policy include: stable marijuana tax funding for Student Assistance Programs (SAPs) in high schools; elimination of "zero-tolerance" suspension/expulsion policies in favor of school retention and academic remediation programs; juvenile justice transparency discriminating among infractions, misdemeanors, and felonies. Criminal sanctions and durations must be proportional to the offense. Probation-based interventions should be reserved for larger possession amounts and recidivist offenders, and outcomes should be independently evaluated. PMID- 26891112 TI - Incidence of hepatocellular carcinoma after seroclearance is not reduced. PMID- 26891113 TI - Duane Retraction Syndrome Associated with a Small X Chromosome Deletion. PMID- 26891114 TI - Determination of metal ions in tea samples using task-specific ionic liquid-based ultrasound-assisted dispersive liquid-liquid microextraction coupled to liquid chromatography with ultraviolet detection. AB - Task-specific ionic liquid-based ultrasound-assisted dispersive liquid-liquid microextraction was used for the preconcentration of cadmium(II), cobalt(II), and lead(II) ions in tea samples, which were subsequently analyzed by liquid chromatography with UV detection. The proposed method of preconcentration is free of volatile organic compounds, which are often used as extractants and dispersing solvents in classic techniques of microextraction. A task-specific ionic liquid trioctylmethylammonium thiosalicylate was used as an extractant and a chelating agent. Ultrasound was used to disperse the ionic liquid. After microextraction, the phases were separated by centrifugation, and the ionic liquid phase was solubilized in methanol and directly injected into the liquid chromatograph. Selected microextraction parameters, such as the volume of ionic liquid, the pH of the sample, the duration of ultrasound treatment, the speed and time of centrifugation, and the effect of ionic strength, were optimized. Under optimal conditions an enrichment factor of 200 was obtained for each analyte. The limits of detection were 0.002 mg/kg for Cd(II), 0.009 mg/kg for Co(II), and 0.013 mg/kg for Pb(II). The accuracy of the proposed method was evaluated by an analysis of the Certified Reference Materials (INCT-TL-1, INCT-MPH-2) with the recovery values in the range of 90-104%. PMID- 26891115 TI - Randomized Controlled Trial Evaluating Dialkylcarbamoyl Chloride Impregnated Dressings for the Prevention of Surgical Site Infections in Adult Women Undergoing Cesarean Section. AB - BACKGROUND: Surgical site infections (SSI) occur in 1.8%-9.2% of women undergoing cesarean section (CS) and lead to greater morbidity rates and increased treatment costs. The aim of the study was to evaluate the efficacy and cost-effectiveness of dialkylcarbamoyl chloride (DACC) impregnated dressings to prevent SSI in women subject to CS. METHODS: Randomized, controlled trial was conducted at the Mazovian Brodno Hospital, a tertiary care center performing approximately 1300 deliveries per year, between June 2014 and April 2015. Patients were randomly allocated to receive either DACC impregnated dressing or standard surgical dressing (SSD) following skin closure. In order to analyze cost-effectiveness of the selected dressings in the group of patients who developed SSI, the costs of ambulatory visits, additional hospitalization, nursing care, and systemic antibiotic therapy were assessed. Independent risk factors for SSI were determined by multivariable logistic regression. RESULTS: Five hundred and forty three women undergoing elective or emergency CS were enrolled. The SSI rates in the DACC and SSD groups were 1.8% and 5.2%, respectively (p = 0.04). The total cost of SSI prophylaxis and treatment was greater in the control group as compared with the study group (5775 EUR vs. 1065 EUR, respectively). Independent risk factors for SSI included higher pre-pregnancy body mass index (adjusted odds ratio [aOR] = 1.08; [95% confidence interval [CI]: 1.0-1.2]; p < 0.05), smoking in pregnancy (aOR = 5.34; [95% CI: 1.6-15.4]; p < 0.01), and SSD application (aOR = 2.94; [95% CI: 1.1-9.3]; p < 0.05). CONCLUSION: The study confirmed the efficacy and cost-effectiveness of DACC impregnated dressings in SSI prevention among women undergoing CS. PMID- 26891116 TI - Interfacial dilatational deformation accelerates particle formation in monoclonal antibody solutions. AB - Protein molecules are amphiphilic moieties that spontaneously adsorb at the air/solution (A/S) interface to lower the surface energy. Previous studies have shown that hydrodynamic disruptions to these A/S interfaces can result in the formation of protein aggregates that are of concern to the pharmaceutical industry. Interfacial hydrodynamic stresses encountered by protein therapeutic solutions under typical manufacturing, filling, and shipping conditions will impact protein stability, prompting a need to characterize the contribution of basic fluid kinematics to monoclonal antibody (mAb) destabilization. We demonstrate that dilatational surface deformations are more important to antibody stability when compared to constant-area shear of the A/S interface. We have constructed a dilatational interfacial rheometer that utilizes simultaneous pressure and bubble shape measurements to study the mechanical stability of mAbs under interfacial aging. It has a distinct advantage over methods utilizing the Young-Laplace equation, which incorrectly describes viscoelastic interfaces. We provide visual evidence of particle ejection from dilatated A/S interfaces and spectroscopic data of ejected mAb particles. These rheological studies frame a molecular understanding of the protein-protein interactions at the complex-fluid interface. PMID- 26891118 TI - Iodine Supplementation of Mildly Iodine-Deficient Adults Lowers Thyroglobulin: A Randomized Controlled Trial. AB - CONTEXT: An inverse relationship between thyroglobulin (Tg) and urinary iodine concentration (UIC) has been found in children, potentially making Tg a viable blood marker of iodine status. The application of Tg in adults is unknown. OBJECTIVE: The objective of the study was to determine the efficacy of Tg to assess iodine status in adults. DESIGN: This was a randomized, double-blind, placebo-controlled, clinical trial. SETTING: The study was conducted in Dunedin, New Zealand. PARTICIPANTS: Mildly iodine deficient adults (n = 112) aged 18-40 years participated in the study. INTERVENTION: Participants were supplemented with 150 MUg of iodine as potassium iodate or placebo daily for 24 weeks. At baseline and 24 weeks, participants provided five casual urine samples for UIC determination; serum TSH and free T4 (FT4) was also measured. Tg was determined at baseline and 8, 16, and 24 weeks. MAIN OUTCOME MEASURES: A change in Tg concentration between the iodine-supplemented and placebo groups at 24 weeks. RESULTS: At baseline, the overall median UIC was 65 MUg/L, confirming that participants were mildly iodine deficient (ie, median UIC between 50 and 99 MUg/L). The overall median Tg was 16.6 MUg/L; TSH and FT4 were within normal reference ranges. At 24 weeks, the median UIC of the placebo and supplemented groups was significantly different, 79 and 168 MUg/L, respectively (P < .001). Tg in the iodine-supplemented group decreased by 12%, 20%, and 27% compared with the placebo group at 8 (P = .045), 16 (P < .001), and 24 weeks (P < .001); there were no significant changes in TSH and FT4. CONCLUSION: Improved iodine status as assessed by UIC was associated with a concomitant decrease in Tg concentration, demonstrating that Tg is a useful biomarker of iodine status in a group of adults. PMID- 26891117 TI - The Oxygen Environment at Birth Specifies the Population of Alveolar Epithelial Stem Cells in the Adult Lung. AB - Alveolar epithelial type II cells (AEC2) maintain pulmonary homeostasis by producing surfactant, expressing innate immune molecules, and functioning as adult progenitor cells for themselves and alveolar epithelial type I cells (AEC1). How the proper number of alveolar epithelial cells is determined in the adult lung is not well understood. Here, BrdU labeling, genetic lineage tracing, and targeted expression of the anti-oxidant extracellular superoxide dismutase in AEC2s are used to show how the oxygen environment at birth influences postnatal expansion of AEC2s and AEC1s in mice. Birth into low (12%) or high (>=60%) oxygen stimulated expansion of AEC2s through self-renewal and differentiation of the airway Scgb1a1 + lineage. This non-linear or hormesis response to oxygen was specific for the alveolar epithelium because low oxygen stimulated and high oxygen inhibited angiogenesis as defined by changes in V-cadherin and PECAM (CD31). Although genetic lineage tracing studies confirmed adult AEC2s are stem cells for AEC1s, we found no evidence that postnatal growth of AEC1s were derived from self-renewing Sftpc + or the Scbg1a1 + lineage of AEC2s. Taken together, our results show how a non-linear response to oxygen at birth promotes expansion of AEC2s through two distinct lineages. Since neither lineage contributes to the postnatal expansion of AEC1s, the ability of AEC2s to function as stem cells for AEC1s appears to be restricted to the adult lung. Stem Cells 2016;34:1396-1406. PMID- 26891119 TI - Progressive Generalized Lipodystrophy as a Manifestation of Autoimmune Polyglandular Syndrome Type 1. AB - We describe APS1 in a boy with generalized lipodystrophy, oral candidiasis, autoimmune hepatitis and adrenal insufficiency. It is the first time when generalized lipodystrophy is associated with APS1. PMID- 26891120 TI - Real social analytics: A contribution towards a phenomenology of a digital world. AB - This article argues against the assumption that agency and reflexivity disappear in an age of 'algorithmic power' (Lash 2007). Following the suggestions of Beer (2009), it proposes that, far from disappearing, new forms of agency and reflexivity around the embedding in everyday practice of not only algorithms but also analytics more broadly are emerging, as social actors continue to pursue their social ends but mediated through digital interfaces: this is the consequence of many social actors now needing their digital presence, regardless of whether they want this, to be measured and counted. The article proposes 'social analytics' as a new topic for sociology: the sociological study of social actors' uses of analytics not for the sake of measurement itself (or to make profit from measurement) but in order to fulfil better their social ends through an enhancement of their digital presence. The article places social analytics in the context of earlier debates about categorization, algorithmic power, and self presentation online, and describes in detail a case study with a UK community organization which generated the social analytics approach. The article concludes with reflections on the implications of this approach for further sociological fieldwork in a digital world. PMID- 26891121 TI - Natural Killer/T Cell Lymphoma, Nasal Type: A Retrospective Clinical Analysis in North-Western China. AB - BACKGROUND: Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is an aggressive non-Hodgkin's lymphoma with high mortality and poor prognosis despite radiotherapy and chemotherapy. The current analysis aimed to assess the pathological features, clinical features, and prognostic indicators of ENKTL. MATERIAL AND METHODS: 120 ENKTL patients were analyzed for pathologic diagnosis and clinical disease manifestations from April 2007 to October 2012. Complete remission, 2-year overall survival, and progression-free survival were analyzed. RESULTS: Compared with the nasal group, a greater percentage of patients in the non-nasal group intended to receive autologous stem cell transplantation had Epstein-Barr virus (EBV) DNA, Ann Arbor stage IV, Ki-67 expression >= 60%, and abnormal ferroprotein and beta-microglobulin levels. The rate of complete remission in the non-nasal group was higher than that in the nasal group. The overall survival rate was 74.9% at 24 months. Patients receiving chemotherapy and radiotherapy were more likely to have disease progression compared with patients who received chemotherapy or radiotherapy alone. CONCLUSIONS: Further understanding the pathological and clinical features of ENKTL will be critical for moving forward. Ki-67, beta-microglobulin, EBV DNA, and primary site prognostic indicators may be useful to stratify patients into different risk groups, to gain insight into patient-specific treatments, and to potentially improve survival. PMID- 26891122 TI - Thyroid calcifications: a pictorial essay. AB - Incidental diagnosis of thyroid nodules is very common on adult neck ultrasonography examination. Thyroid calcifications are encountered in benign thyroid nodules and goiters as well as in thyroid malignancy. Depiction and characterization of such calcifications within a thyroid nodule may be a key element in the thyroid nodule diagnosis algorithm. The goal of this paper is to display typical radio-pathological correlations of various thyroid pathologies of benign and malignant conditions in which the calcification type diagnosis can play a key role in the final diagnosis of the thyroid nodule. PMID- 26891123 TI - Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding. AB - BACKGROUND: The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (<=3 months) period after BS in morbid obesity. METHOD: In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS: Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS: Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term. PMID- 26891125 TI - Go Forth and Colonize: Dispersal from Clinically Important Microbial Biofilms. PMID- 26891124 TI - Carvedilol Improves Inflammatory Response, Oxidative Stress and Fibrosis in the Alcohol-Induced Liver Injury in Rats by Regulating Kuppfer Cells and Hepatic Stellate Cells. AB - AIM: To evaluate the anti-inflammatory, anti-oxidant and antifibrotic effects of carvedilol (CARV) in rats with ethanol-induced liver injury. METHODS: Liver injury was induced by gavage administration of alcohol (7 g/kg) for 28 consecutive days. Eighty Wistar rats were pretreated with oral CARV at 1, 3, or 5 mg/kg or with saline 1 h before exposure to alcohol. Liver homogenates were assayed for interleukin (IL)-1beta, IL-10, and tumor necrosis factor (TNF)-alpha level as well as for myeloperoxidase (MPO) activity and malonyldialdehyde (MDA) and glutathione (GSH) levels. Serum aspartate aminotransferase (AST) activity and liver triglyceride (TG) levels were also assayed. Immunohistochemical analyses of cyclooxygenase 2 (COX-2), receptor activator of nuclear factor kappa-B/ligand (RANK/RANKL), suppressor of cytokine signalling (SOCS1), the Kupffer cell marker IBA-1 (ionized calcium-binding adaptor molecule 1), intercellular adhesion molecule 1 (ICAM-1), superoxide dismutase (SOD-1), and glutathione peroxidase (GPx-1) expression were performed. Confocal microscopy analysis of IL-1beta and NF-kappaB expression and real-time quantitative PCR analysis for TNFalpha, PCI, PCIII, and NF-kappaB were performed. RESULTS: CARV treatment (5 mg/kg) during the alcohol exposure protocol was associated with reduced steatosis, hepatic cord degeneration, fibrosis and necrosis, as well as reduced levels of AST (p < 0.01), ALT (p < 0.01), TG (p < 0.001), MPO (p < 0.001), MDA (p < 0.05), and proinflammatory cytokines (IL-1beta and TNF-alpha, both p < 0.05), and increased levels of the anti-inflammatory cytokine IL-10 (p < 0.001) and GSH (p < 0.05), compared to the alcohol-only group. Treatment with CARV 5 mg/kg also reduced expression levels of COX-2, RANK, RANKL, IBA-1, and ICAM-1 (all p < 0.05), while increasing expression of SOCS1, SOD-1, and GPx-1 (all p < 0.05) and decreasing expression of IL-1beta and NF-kappaB (both, p < 0.05). Real-time quantitative PCR analysis showed that mRNA production of TNF-alpha, procollagen type I (PCI), procollagen type III (PCIII), and NF-kappaB were decreased in the alcohol-CARV 5 mg/kg group relative to the alcohol-only group. CONCLUSIONS: CARV can reduce the stress oxidative, inflammatory response and fibrosis in ethanol-induced liver injury in a rat model by downregulating signalling of Kuppfer cells and hepatic stellate cells (HSCs) through suppression of inflammatory cytokines. PMID- 26891127 TI - Mass Spectrometry Imaging of the Hypoxia Marker Pimonidazole in a Breast Tumor Model. AB - Although tumor hypoxia is associated with tumor aggressiveness and resistance to cancer treatment, many details of hypoxia-induced changes in tumors remain to be elucidated. Mass spectrometry imaging (MSI) is a technique that is well suited to study the biomolecular composition of specific tissue regions, such as hypoxic tumor regions. Here, we investigate the use of pimonidazole as an exogenous hypoxia marker for matrix-assisted laser desorption/ionization (MALDI) MSI. In hypoxic cells, pimonidazole is reduced and forms reactive products that bind to thiol groups in proteins, peptides, and amino acids. We show that a reductively activated pimonidazole metabolite can be imaged by MALDI-MSI in a breast tumor xenograft model. Immunohistochemical detection of pimonidazole adducts on adjacent tissue sections confirmed that this metabolite is localized to hypoxic tissue regions. We used this metabolite to image hypoxic tissue regions and their associated lipid and small molecule distributions with MALDI-MSI. We identified a heterogeneous distribution of 1-methylnicotinamide and acetylcarnitine, which mostly colocalized with hypoxic tumor regions. As pimonidazole is a widely used immunohistochemical marker of tissue hypoxia, it is likely that the presented direct MALDI-MSI approach is also applicable to other tissues from pimonidazole injected animals or humans. PMID- 26891126 TI - A radial sampling strategy for uniform k-space coverage with retrospective respiratory gating in 3D ultrashort-echo-time lung imaging. AB - The purpose of this work was to develop a 3D radial-sampling strategy which maintains uniform k-space sample density after retrospective respiratory gating, and demonstrate its feasibility in free-breathing ultrashort-echo-time lung MRI. A multi-shot, interleaved 3D radial sampling function was designed by segmenting a single-shot trajectory of projection views such that each interleaf samples k space in an incoherent fashion. An optimal segmentation factor for the interleaved acquisition was derived based on an approximate model of respiratory patterns such that radial interleaves are evenly accepted during the retrospective gating. The optimality of the proposed sampling scheme was tested by numerical simulations and phantom experiments using human respiratory waveforms. Retrospectively, respiratory-gated, free-breathing lung MRI with the proposed sampling strategy was performed in healthy subjects. The simulation yielded the most uniform k-space sample density with the optimal segmentation factor, as evidenced by the smallest standard deviation of the number of neighboring samples as well as minimal side-lobe energy in the point spread function. The optimality of the proposed scheme was also confirmed by minimal image artifacts in phantom images. Human lung images showed that the proposed sampling scheme significantly reduced streak and ring artifacts compared with the conventional retrospective respiratory gating while suppressing motion-related blurring compared with full sampling without respiratory gating. In conclusion, the proposed 3D radial-sampling scheme can effectively suppress the image artifacts due to non-uniform k-space sample density in retrospectively respiratory-gated lung MRI by uniformly distributing gated radial views across the k-space. PMID- 26891129 TI - Anatomical liver resection of segment 4a en bloc with the caudate lobe. AB - Anatomical segmentectomy is the complete resection of an area supplied by a segmental portal branch. Among segmentectomies, isolated segmentectomy 4 is a technically demanding procedure because there are two transection planes: on the left side along the umbilical fissure and, on the right side, along the middle hepatic vein. Although there are several reports on anatomic segmentectomies, only few regard the anatomic segmentectomy 4a. We report here the case of a 60 year-old man who underwent anatomical segmentectomy 4a en bloc with the caudate lobe to resect a colorectal liver metastasis located in segment 4a and involving the paracaval portion of the caudate lobe. This type of procedure was planned in order to maximize the postoperative functional hepatic reserve, thereby reducing the risk of postoperative liver failure and ultimately allowing the possibility for future repeat hepatectomy in case of recurrence. J. Surg. Oncol. 2016;113:665 667. (c) 2016 Wiley Periodicals, Inc. PMID- 26891128 TI - Identification of Novel Reference Genes Suitable for qRT-PCR Normalization with Respect to the Zebrafish Developmental Stage. AB - Reference genes used in normalizing qRT-PCR data are critical for the accuracy of gene expression analysis. However, many traditional reference genes used in zebrafish early development are not appropriate because of their variable expression levels during embryogenesis. In the present study, we used our previous RNA-Seq dataset to identify novel reference genes suitable for gene expression analysis during zebrafish early developmental stages. We first selected 197 most stably expressed genes from an RNA-Seq dataset (29,291 genes in total), according to the ratio of their maximum to minimum RPKM values. Among the 197 genes, 4 genes with moderate expression levels and the least variation throughout 9 developmental stages were identified as candidate reference genes. Using four independent statistical algorithms (delta-CT, geNorm, BestKeeper and NormFinder), the stability of qRT-PCR expression of these candidates was then evaluated and compared to that of actb1 and actb2, two commonly used zebrafish reference genes. Stability rankings showed that two genes, namely mobk13 (mob4) and lsm12b, were more stable than actb1 and actb2 in most cases. To further test the suitability of mobk13 and lsm12b as novel reference genes, they were used to normalize three well-studied target genes. The results showed that mobk13 and lsm12b were more suitable than actb1 and actb2 with respect to zebrafish early development. We recommend mobk13 and lsm12b as new optimal reference genes for zebrafish qRT-PCR analysis during embryogenesis and early larval stages. PMID- 26891130 TI - Intracochlear Position of Cochlear Implants Determined Using CT Scanning versus Fitting Levels: Higher Threshold Levels at Basal Turn. AB - OBJECTIVES: In this study, the effects of the intracochlear position of cochlear implants on the clinical fitting levels were analyzed. DESIGN: A total of 130 adult subjects who used a CII/HiRes 90K cochlear implant with a HiFocus 1/1J electrode were included in the study. The insertion angle and the distance to the modiolus of each electrode contact were determined using high-resolution CT scanning. The threshold levels (T-levels) and maximum comfort levels (M-levels) at 1 year of follow-up were determined. The degree of speech perception of the subjects was evaluated during routine clinical follow-up. RESULTS: The depths of insertion of all the electrode contacts were determined. The distance to the modiolus was significantly smaller at the basal and apical cochlear parts compared with that at the middle of the cochlea (p < 0.05). The T-levels increased toward the basal end of the cochlea (3.4 dB). Additionally, the M levels, which were fitted in our clinic using a standard profile, also increased toward the basal end, although with a lower amplitude (1.3 dB). Accordingly, the dynamic range decreased toward the basal end (2.1 dB). No correlation was found between the distance to the modiolus and the T-level or the M-level. Furthermore, the correlation between the insertion depth and stimulation levels was not affected by the duration of deafness, age at implantation or the time since implantation. Additionally, the T-levels showed a significant correlation with the speech perception scores (p < 0.05). CONCLUSIONS: The stimulation levels of the cochlear implants were affected by the intracochlear position of the electrode contacts, which were determined using postoperative CT scanning. Interestingly, these levels depended on the insertion depth, whereas the distance to the modiolus did not affect the stimulation levels. The T-levels increased toward the basal end of the cochlea. The level profiles were independent of the overall stimulation levels and were not affected by the biographical data of the patients, such as the duration of deafness, age at implantation or time since implantation. Further research is required to elucidate how fitting using level profiles with an increase toward the basal end of the cochlea benefits speech perception. Future investigations may elucidate an explanation for the effects of the intracochlear electrode position on the stimulation levels and might facilitate future improvements in electrode design. PMID- 26891132 TI - Revealing the Formation of Copper Nanoparticles from a Homogeneous Solid Precursor by Electron Microscopy. AB - The understanding of processes leading to the formation of nanometer-sized particles is important for tailoring of their size, shape and location. The growth mechanisms and kinetics of nanoparticles from solid precursors are, however, often poorly described. Here we employ transmission electron microscopy (TEM) to examine the formation of copper nanoparticles on a silica support during the reduction by H2 of homogeneous copper phyllosilicate platelets, as a prototype precursor for a coprecipitated catalyst. Specifically, time-lapsed TEM image series acquired of the material during the reduction process provide a direct visualization of the growth dynamics of an ensemble of individual nanoparticles and enable a quantitative evaluation of the nucleation and growth of the nanoparticles. This quantitative information is compared with kinetic models and found to be best described by a nucleation-and-growth scenario involving autocatalytic reduction of the copper phyllosilicate followed by diffusion-limited or reaction-limited growth of the copper nanoparticles. The plate-like structure of the precursor restricted the diffusion of copper and the autocatalytic reduction limited the probability for secondary nucleation. The combination of a uniform size of precursor particles and the autocatalytic reduction thus offers means to synthesize nanoparticles with well-defined sizes in large amounts. In this way, in situ observations made by electron microscopy provide mechanistic and kinetic insights into the formation of supported nanoparticles, essential for the rational design of nanomaterials. PMID- 26891131 TI - Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12. AB - Uterine leiomyosarcomas (ULMSs) are aggressive smooth muscle tumors associated with poor clinical outcome. Despite previous cytogenetic and molecular studies, their molecular background has remained elusive. To examine somatic variation in ULMS, we performed exome sequencing on 19 tumors. Altogether, 43 genes were mutated in at least two ULMSs. Most frequently mutated genes included tumor protein P53 (TP53; 6/19; 33%), alpha thalassemia/mental retardation syndrome X linked (ATRX; 5/19; 26%), and mediator complex subunit 12 (MED12; 4/19; 21%). Unlike ATRX mutations, both TP53 and MED12 alterations have repeatedly been associated with ULMSs. All the observed ATRX alterations were either nonsense or frameshift mutations. ATRX protein levels were reliably analyzed by immunohistochemistry in altogether 44 ULMSs, and the majority of tumors (23/44; 52%) showed clearly reduced expression. Loss of ATRX expression has been associated with alternative lengthening of telomeres (ALT), and thus the telomere length was analyzed with telomere-specific fluorescence in situ hybridization. The ALT phenotype was confirmed in all ULMSs showing diminished ATRX expression. Exome data also revealed one nonsense mutation in death-domain associated protein (DAXX), another gene previously associated with ALT, and the tumor showed ALT positivity. In conclusion, exome sequencing revealed that TP53, ATRX, and MED12 are frequently mutated in ULMSs. ALT phenotype was commonly seen in tumors, indicating that ATR inhibitors, which were recently suggested as possible new drugs for ATRX-deficient tumors, could provide a potential novel therapeutic option for ULMS. PMID- 26891133 TI - Caffeine intake enhances the benefits of sodium glucose transporter 2 inhibitor. AB - BACKGROUND: The effect of sodium glucose transporter 2 (SGLT-2) inhibitors is dependent on the glomerular filtration rate. It has been reported that caffeine intake increases glomerular filtration rate. However, the effect of caffeine intake on urinary glucose excretion in patients who take SGLT-2 inhibitors is unclear. METHODS: Six patients with type 2 diabetes took part in a randomized, open-label, crossover pilot study. The patients took SGLT-2 inhibitors (ipragliflozin) for 9 days. On day 3, 6 and 9, the patients were assigned to one of three studies: Water 500, patients drank 500 mL of water in 3 h; Water 1500, patients drank 1500 mL of water in 3 h; and Caffeine 500, patients drank 500 mL of water with 400 mg of caffeine in 3 h. In all of the studies, the patients' urine was collected over a 6-h period. In addition, we enrolled 60 patients with type 2 diabetes who newly took SGLT-2 inhibitors in a 3-month follow-up cohort study to investigate the effect of caffeine intake on glucose control. Caffeine intake was evaluated using questionnaires. RESULTS: The 6-h median (interquartile range) urinary glucose excretion was 9.5 (8.5-9.7) g in Water 500, 12.2 (10.3 27.2) g in Water 1500 and 15.7 (11.4-21.4) g in Caffeine 500 (p = 0.005 vs Water 500). In the cohort study, multiple regression analysis demonstrated that log (caffeine intake) was associated with a change in HbA1c (beta = -0.299, p = 0.043) after adjusting for covariates. CONCLUSIONS: Caffeine intake enhanced the effect of SGLT-2 inhibitors. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891135 TI - Urban Myths in Plastic Surgery: Postoperative Management of Surgical Drains. AB - BACKGROUND: Surgical patients are frequently discharged with surgical drains to assist in wound closure that could be disrupted by postoperative hematomas, lymphoceles, or seromas. In clinical practice, duration of drain use is typically dependent on daily output. OBJECTIVE: The aim of this paper was to examine the origins and justifications of drain removal criteria. The authors considered factors that may influence recommendations such as duration, area of surgical site, and risk of infection. METHODS: A literature review was performed regarding the indications for drain removal in patients undergoing reconstructive and breast surgeries. PubMed was queried for publications up to May 2015 with the following search terms: drain removal, hematomas, lymphoceles, seroma, volume, reconstruction, and mastectomy. Clinical trials, retrospective reviews, meta analyses, and literature reviews were included. RESULTS: Most plastic surgeons remove drains based on volume criteria; however, some evidence supports early, fixed-duration drain removal. Patients who produce large volumes of fluid from the surgical site are more likely to continue to do so after drain removal and may require increased duration of drain use. Surgical site surface area may also be a factor to consider when pulling a drain. CONCLUSION: Though drain-associated infection rates are low and appear unaffected by duration, poor outcomes such as implant loss and need for reoperation may be mitigated by antisepsis strategies. PMID- 26891134 TI - Generalized Cowpox Virus Infection in a Patient with HIV, Germany, 2012. PMID- 26891136 TI - Flow-through Instillation of Hypochlorous Acid in the Treatment of Necrotizing Fasciitis. AB - INTRODUCTION: Necrotizing fasciitis (NF) is a rare and rapidly progressing bacterial infection of soft tissues. Bacterial toxins cause local tissue damage and necrosis, as well as blunt immune system responses. A self-propagating cycle of bacterial invasion, toxin release and tissue destruction can continue until substantial amounts of tissue become necrotic. Neutralization of bacterial toxins should improve the results. MATERIALS AND METHODS: Pure hypochlorous acid (HOCl) (0.01% w/v) with no sodium hypochlorite impurity in saline pH 4-5, which was recently shown to both eradicate bacteria and neutralize bacterial toxins in vitro, was administered via flowthrough instillation to 6 patients with NF 4-6 times daily as needed. Utilizing a vacuum-assisted closure, 5-10 mL of pure 0.01% HOCl with no sodium hypochlorite impurity was instilled and removed frequently to irrigate the wounds. RESULTS: Of the 6 patients, no deaths or limb amputations occurred. All infected areas healed completely without major complications. CONCLUSION: The toxicity and immune dysfunction caused by bacterial toxins and toxins released from damaged cells may be mitigated by flow-through instillation with saline containing pure 0.01% HOCl with no sodium hypochlorite impurity. Randomized controlled clinical trial research of this relatively simple and inexpensive instillation protocol is suggested for identified cases of NF. PMID- 26891137 TI - A Simplified Vacuum Dressing System. AB - Negative pressure wound therapy (NPWT) may not necessarily require sophisticated equipment. In settings with limited medical resources, simplified vacuum dressings have been considered an effective alternative to the gold-standard vacuum-assisted closure system. The aim of this study was to evaluate the performance of a simplified vacuum dressing system in the treatment of complex wounds. MATERIALS AND METHODS: This was a prospective study in which difficult-to manage wounds were treated using a simplified vacuum dressing system. Thirty-nine patients with a total of 51 wounds were treated. The main complications were pain (15.7%), bleeding (9.6%), and extremity edema (5.2%). After NPWT, the wounds were closed by skin grafting or with a skin flap in 71.8% of patients. RESULTS: The results of NPWT were considered satisfactory in 87.2% of cases. The use of a simplified vacuum dressing system provided satisfactory results in the treatment of complex wounds in the studied population. CONCLUSION: The system proved easy to use, had a low complication rate and excellent costeffectiveness, and it may be considered as an effective alternative to the gold-standard vacuum-assisted closure system for patients requiring prolonged hospitalization due to the presence of extensive wounds that cannot be treated at home. PMID- 26891138 TI - Point Prevalence of Chronic Wounds at a Tertiary Hospital in Nigeria. AB - BACKGROUND: Chronic wounds are a drain on resources both for the patient and health institution. Management of chronic wounds based on evidence-based practice requires baseline data for adequate planning. OBJECTIVES: This study was carried out to determine the point prevalence of chronic wounds in a tertiary hospital (University College Hospital, Ibadan, Nigeria) and utilize this information for subsequent wound care planning. METHODS: The study was carried out within a 1 month period and included all patients seen in the hospital with chronic wounds. The data obtained was entered into a designed form and was subsequently analyzed. RESULTS: There were 48 patients with 78 wounds representing approximately 11% of patients seen in the Department of Plastic, Reconstructive, and Aesthetic Surgery each month. Their ages ranged from 3 months to 80 years; the median age was 48 years. The male to female ratio was 1.6 to 1. The duration of the wounds ranged from 6 weeks to 780 weeks; the median duration of the wounds was 10 weeks. The area of the wounds ranged from 1 cm(2) -1,248 cm(2) (median 24 cm(2)). The most common chronic wounds were diabetic wounds, followed by pressure ulcers, postinfection ulcers, posttraumatic ulcers, burn wounds, malignant ulcers, and venous ulcers. CONCLUSION: The point prevalence data serves as a basis for wound care planning. This, in turn, should result in improved wound management grounded in evidence-based practices. PMID- 26891139 TI - Factitious Ulcer Misdiagnosed as Pyoderma Gangrenosum. AB - Dermatitis artefacta may represent a real challenge for the clinician. As the patient does not admit self-inflicting the lesions, misdiagnosis with other diseases, such as pyoderma gangrenosum, is common. Consequently, these patients normally go through unnecessary tests and receive potentially harmful treatments as clinicians determine their diagnosis. The authors present the case of a recurrent factitious abdominal ulcer that was initially diagnosed and treated as pyoderma gangrenosum. This report focuses on the necessity of suspecting dermatitis artefacta when morphology, history, and treatment failures are difficult to explain. It is essential to establish a supportive and confident approach and avoid initial confrontation. In-patient treatment may be useful and long-term followup may prevent recurrences. PMID- 26891140 TI - A Firm and Painful Plaque on the Thorax: The Role of Ultrasound in the Detection of Foreign Bodies. AB - The presence of a subcutaneous foreign body may not be easily suspected after the initial history and exploration of the patient. The authors report a 54-year-old male who came to the Department of Dermatology, Hospital Universitario de Fuenlabrada, Madrid, Spain with a firm plaque, fixed to deep structures, which showed several draining orifices over the costal grid. After several tests, the authors performed an ultrasonography that revealed the presence of a fistula from a foreign body secondary to a previously untreated costal fracture that occurred several years before. The authors believe ultrasonography is a readily available and useful tool that may help dermatologists in daily clinical practice, with the advantage of being a noninvasive test. PMID- 26891142 TI - Unique Solvent Effects on Visible-Light CO2 Reduction over Ruthenium(II) Complex/Carbon Nitride Hybrid Photocatalysts. AB - Photocatalytic CO2 reduction using hybrids of carbon nitride (C3N4) and a Ru(II) complex under visible light was studied with respect to reaction solvent. Three different Ru(II) complexes, trans(Cl)-[Ru(X2bpy) (CO)2Cl2] (X2bpy = 2,2' bipyridine with substituents X in the 4-positions, X = COOH, PO3H2, or CH2PO3H2), were employed as promoters and will be abbreviated as RuC (X = COOH), RuP (X = PO3H2), and RuCP (X = CH2PO3H2). When C3N4 modified with a larger amount of RuCP (>7.8 MUmol g(-1)) was employed as a photocatalyst in a solvent having a relatively high donor number (e.g., N,N-dimethylacetamide (DMA), N,N dimethylformamide (DMF), and dimethyl sulfoxide (DMSO)) with the aid of triethanolamine (TEOA) as an electron donor, the hybrid photocatalyst exhibited high performance for CO2 reduction, producing CO and HCOOH with relatively high CO selectivity (40-70%). On the other hand, HCOOH was the major product when RuC/C3N4 or RuP/C3N4 was employed regardless of the loading amount of the Ru(II) complex and the reaction solvent. Results of photocatalytic reactions and UV visible diffuse reflectance spectroscopy indicated that polymeric Ru species, which were formed in situ from RuCP on C3N4 under irradiation in a solvent having a high donor number, were active catalysts for CO formation. Nonsacrificial CO2 reduction using RuP/C3N4 was accomplished in a DMA solution containing methanol as an electron donor, which means that visible light energy was stored as chemical energy in the form of CO and formaldehyde (DeltaG degrees = +67.6 kJ mol(-1)). This study demonstrated the first successful example of an energy conversion scheme using carbon nitride through photocatalytic CO2 reduction. PMID- 26891141 TI - Exudative cotton wool spots: an under-recognized variant of a common lesion. PMID- 26891143 TI - An overview of pharmaceutical patent litigation in China. PMID- 26891144 TI - Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease. AB - The epithelial barrier is the first innate defense of the gastrointestinal tract and selectively regulates transport from the lumen to the underlying tissue compartments, restricting the transport of smaller molecules across the epithelium and almost completely prohibiting epithelial macromolecular transport. This selectivity is determined by the mucous gel layer, which limits the transport of lipophilic molecules and both the apical receptors and tight junctional protein complexes of the epithelium. In vitro cell culture models of the epithelium are convenient, but as a model, they lack the complexity of interactions between the microbiota, mucous-gel, epithelium and immune system. On the other hand, in vivo assessment of intestinal absorption or permeability may be performed, but these assays measure overall gastrointestinal absorption, with no indication of site specificity. Ex vivo permeability assays using "intestinal sacs" are a rapid and sensitive method of measuring either overall intestinal integrity or comparative transport of a specific molecule, with the added advantage of intestinal site specificity. Here we describe the preparation of intestinal sacs for permeability studies and the calculation of the apparent permeability (Papp) of a molecule across the intestinal barrier. This technique may be used as a method of assessing drug absorption, or to examine regional epithelial barrier dysfunction in animal models of gastrointestinal disease. PMID- 26891145 TI - Iridium-Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (-)-Aspidophylline A. AB - The first enantioselective total synthesis of (-)-aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3-disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C-H activation conditions. PMID- 26891146 TI - Rapid induction of apoptosis in chronic lymphocytic leukemia cells by the microtubule disrupting agent BNC105. AB - Microtubule targeting agents, such as vinblastine, are usually thought to arrest cells in mitosis and subsequently induce apoptosis. However, they can also cause rapid induction of apoptosis in a cell-cycle phase independent manner. BNC105 is a novel vascular and microtubule disrupting drug that also induces apoptosis rapidly but with markedly increased potency compared to vinca alkaloids and combretastatin A4. BNC105 binds to the colchicine-binding site on tubulin resulting in activation of c-Jun N-terminal kinase (JNK), phosphorylation of ATF2, and induction of ATF3 and Noxa leading to acute apoptosis in chronic lymphocytic leukemia (CLL) cells. Apoptosis induced by BNC105 is dependent upon both JNK activation and Noxa induction. Normal leukocytes and one CLL sample also exhibited JNK activation but not Noxa induction and were resistant to BNC105. This study emphasizes the importance of Noxa and JNK for induction of apoptosis in CLL cells by microtubule targeting drugs, and highlights the potential of BNC105 as a potent therapeutic to treat haematopoietic malignancies. PMID- 26891147 TI - Modeling Chemotherapy Resistant Leukemia In Vitro. AB - It is well established that the bone marrow microenvironment provides a unique site of sanctuary for hematopoietic diseases that both initiate and progress in this site. The model presented in the current report utilizes human primary bone marrow stromal cells and osteoblasts as two representative cell types from the marrow niche that influence tumor cell phenotype. The in vitro co-culture conditions described for human leukemic cells with these primary niche components support the generation of a chemoresistant subpopulation of tumor cells that can be efficiently recovered from culture for analysis by diverse techniques. A strict feeding schedule to prevent nutrient fluxes followed by gel type 10 cross linked dextran (G10) particles recovery of the population of tumor cells that have migrated beneath the adherent bone marrow stromal cells (BMSC) or osteoblasts (OB) generating a "phase dim" (PD) population of tumor cells, provides a consistent source of purified therapy resistant leukemic cells. This clinically relevant population of tumor cells can be evaluated by standard methods to investigate apoptotic, metabolic, and cell cycle regulatory pathways as well as providing a more rigorous target in which to test novel therapeutic strategies prior to pre-clinical investigations targeted at minimal residual disease. PMID- 26891148 TI - Effect of Character-Audience Similarity on the Perceived Effectiveness of Antismoking PSAs via Engagement. AB - This study assesses the impact of character-audience similarity, a core aspect of tailored communication, on evaluation of antismoking public service announcements (PSAs). Smoker and persuader characters are distinguished to explore their different roles in message effectiveness. Daily adult smokers (n = 1,160) were exposed to four video PSAs randomly selected from a larger pool. Similarity scores were determined from matching in demographic (age, gender, race) and motivational factors (quitting status) between the audience and the PSA's characters. Results show that PSAs featuring distinctive smoker and/or persuader characters yielded significantly higher message engagement and perceived effectiveness (PE) than PSAs without characters. Given the presence of characters, smoker-audience similarity was positively associated with the engagement, which in turn enhanced PE. Persuader-audience similarity failed to predict increases in either engagement or PE. PMID- 26891150 TI - Effect of Exogenous Albumin on the Incidence of Postoperative Acute Kidney Injury in Patients Undergoing Off-pump Coronary Artery Bypass Surgery with a Preoperative Albumin Level of Less Than 4.0 g/dl. AB - BACKGROUND: Hypoalbuminemia may increase the risk of acute kidney injury (AKI). The authors investigated whether the immediate preoperative administration of 20% albumin solution affects the incidence of AKI after off-pump coronary artery bypass surgery. METHODS: In this prospective, single-center, randomized, parallel arm double-blind trial, 220 patients with preoperative serum albumin levels less than 4.0 g/dl were administered 100, 200, or 300 ml of 20% human albumin according to the preoperative serum albumin level (3.5 to 3.9, 3.0 to 3.4, or less than 3.0 g/dl, respectively) or with an equal volume of saline before surgery. The primary outcome measure was AKI incidence after surgery. Postoperative AKI was defined by maximal AKI Network criteria based on creatinine changes. RESULTS: Patient characteristics and perioperative data except urine output during surgery were similar between the two groups studied, the albumin group and the control group. Urine output (median [interquartile range]) during surgery was higher in the albumin group (550 ml [315 to 980]) than in the control group (370 ml [230 to 670]; P = 0.006). The incidence of postoperative AKI in the albumin group was lower than that in the control group (14 [13.7%] vs. 26 [25.7%]; P = 0.048). There were no significant between-group differences in severe AKI, including renal replacement therapy, 30-day mortality, and other clinical outcomes. There were no significant adverse events. CONCLUSION: Administration of 20% exogenous albumin immediately before surgery increases urine output during surgery and reduces the risk of AKI after off-pump coronary artery bypass surgery in patients with a preoperative serum albumin level of less than 4.0 g/dl. PMID- 26891149 TI - Epigenetic silencing of AKAP12 in juvenile myelomonocytic leukemia. AB - A-kinase anchor protein 12 (AKAP12) is a regulator of protein kinase A and protein kinase C signaling, acting downstream of RAS. Epigenetic silencing of AKAP12 has been demonstrated in different cancer entities and this has been linked to the process of tumorigenesis. Here, we used quantitative high resolution DNA methylation measurement by MassARRAY to investigate epigenetic regulation of all three AKAP12 promoters (i.e., alpha, beta, and gamma) within a large cohort of juvenile myelomonocytic leukemia (JMML) patient samples. The AKAP12alpha promoter shows DNA hypermethylation in JMML samples, which is associated with decreased AKAP12alpha expression. Promoter methylation of AKAP12alpha correlates with older age at diagnosis, elevated levels of fetal hemoglobin and poor prognosis. In silico screening for transcription factor binding motifs around the sites of most pronounced methylation changes in the AKAP12alpha promoter revealed highly significant scores for GATA-2/-1 sequence motifs. Both transcription factors are known to be involved in the haematopoietic differentiation process. Methylation of a reporter construct containing this region resulted in strong suppression of AKAP12 promoter activity, suggesting that DNA methylation might be involved in the aberrant silencing of the AKAP12 promoter in JMML. Exposure to DNMT- and HDAC-inhibitors reactivates AKAP12alpha expression in vitro, which could potentially be a mechanism underlying clinical treatment responses upon demethylating therapy. Together, these data provide evidence for epigenetic silencing of AKAP12alpha in JMML and further emphasize the importance of dysregulated RAS signaling in JMML pathogenesis. PMID- 26891151 TI - Symptoms and their recognition in adult haemodialysis patients: Interactions with quality of life. AB - AIM: We investigated the symptom burden in adults on haemodialysis, the recognition of symptoms by nurses and nephrologists, and the relationship between symptoms and quality of life. METHODS: In this cross-sectional observational study, symptoms and quality of life in haemodialysis patients were determined using validated surveys. Nurses and nephrologists independently estimated their patients' symptoms, and these estimates were compared with patient responses (sensitivity; kappa values for interrater agreement). Associations between symptoms and quality of life were assessed using multi-level regression. RESULTS: Forty-three patients, 18 nurses and 3 nephrologists participated. The commonest symptoms (95%CI) reported by patients were weakness, 69% (53 to 82); poor mobility, 44% (29 to 60); and drowsiness, 44% (29 to 60). Sensitivity less than 50% was seen towards 11 of 17 symptoms in nurse ratings compared with 15 of 17 in nephrologist ratings. Agreement with patient symptom ratings was mostly 'fair' (0.21-0.4), with nurses' scores showing greater agreement than nephrologists'. Physical, mental and kidney disease component summary scores of quality of life were negatively associated with total symptom score and the number of 'major' symptoms (r2 values 0.3-0.36); while with multivariate regression, 50% to 60% of the variance in these scores was accounted for by parsimonious models containing symptoms such as pain and poor mobility. CONCLUSION: Symptom burden worsened quality of life scores in haemodialysis patients. Clinician recognition of symptom burden was inaccurate, although nurses were more accurate than nephrologists. Using patient-completed surveys or including dialysis nurse feedback in routine outpatient settings may help improve symptom recognition by nephrologists. PMID- 26891153 TI - Cognitive impairment and mortality among the oldest-old Chinese. AB - OBJECTIVE: This study examined the relationship between cognitive impairment status and all-cause mortality among the oldest-old Chinese. METHODS: A total of 7474 survey participants 80 years of age and above came from the Chinese Longitudinal Healthy Longevity Survey 1998-2012 waves. Baseline cognitive impairment status was assessed using the Chinese version of the mini-mental state examination (MMSE), with total score ranging from 0 to 30. Cox proportional hazards regressions were performed to examine the relationship between baseline cognitive impairment status in 1998 and subsequent all-cause mortality during 1998-2012, adjusting for various individual characteristics at baseline. RESULTS: Compared with those with no or mild cognitive impairment (18 <= MMSE score <= 30) at baseline, participants with moderate-to-severe cognitive impairment (0 <= MMSE score <= 17) were 28% (95% confidence interval = 20%, 37%) more likely to die during the follow-up period from 1998 to 2012. A dose-response relationship between baseline severity level of cognitive impairment and mortality was evident. Compared with those without cognitive impairment (25 <= MMSE score <= 30) at baseline, those having mild cognitive impairment (18 <= MMSE score <= 24), moderate cognitive impairment (10 <= MMSE score <= 17), and severe cognitive impairment (0 <= MMSE score <= 9), were 20% (13%, 28%), 38% (27%, 51%), and 47% (33%, 62%) more likely to die during the follow-up period. No statistically significant gender differences in the relationship between cognitive impairment status and mortality were found. CONCLUSION: Baseline cognitive impairment was inversely associated with longevity among the oldest-old Chinese. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891152 TI - Remarkable Charge Separation and Photocatalytic Efficiency Enhancement through Interconnection of TiO2 Nanoparticles by Hydrothermal Treatment. AB - Although tremendous effort has been directed to synthesizing advanced TiO2 , it remains difficult to obtain TiO2 exhibiting a photocatalytic efficiency higher than that of P25, a benchmark photocatalyst. P25 is composed of anatase, rutile, and amorphous TiO2 particles, and photoexcited electron transfer and subsequent charge separation at the anatase-rutile particle interfaces explain its high photocatalytic efficiency. Herein, we report on a facile and rational hydrothermal treatment of P25 to selectively convert the amorphous component into crystalline TiO2 , which is deposited between the original anatase and rutile particles to increase the particle interfaces and thus enhance charge separation. This process produces a new TiO2 exhibiting a considerably enhanced photocatalytic efficiency. This method of synthesizing this TiO2 , inspired by a recently burgeoning zeolite design, promises to make TiO2 applications more feasible and effective. PMID- 26891154 TI - Trading scalpels for sheaths: Catheter-based treatment of vascular injury can be effectively performed by acute care surgeons trained in endovascular techniques. AB - BACKGROUND: The skill set of the acute care surgeon can be expanded by formal training. We report the first series of traumatic vascular injury (TVI) treated by acute care surgeons trained in endovascular techniques (ACSTEV). METHODS: We retrospectively reviewed patients admitted to our trauma center with TVI over 5 months who survived for more than 24 hours and had catheter diagnosis and/or therapy by ACSTEV. Demographics, admission data, and outcomes were reviewed. Follow-up ranged from 0 day to 150 days. RESULTS: Most patients were male (63%) and sustained blunt mechanism (91%). Mean (SD) age was 48.2 (21.9) years, and mean (SD) Injury Severity Score was 32.1 (11.8). Mean (SD) admission systolic blood pressure, heart rate, Glasgow Coma Scale (GCS) score were 126.12 (30.4) mm Hg, 101.21 (28.2) beats per minute, and 10.8 (4.73), respectively. Forty-six patients underwent 48 endovascular procedures for TVI: 32 angiograms and 16 venograms were obtained. Two pelvic angiograms and one aortic arch angiogram were negative and required no treatment. One superficial femoral artery arteriogram showed minor luminal defects requiring anticoagulation only. Pseudoaneurysms were found in 17 vessels, vessel truncation in 4, active extravasation in 5, stenosis in 1, and dissection with thrombus in 1. Four patients had resuscitative endovascular balloon occlusion of the aorta performed before catheter intervention for pelvic hemorrhage. Procedures included aortic repair (4), pelvic embolization (13), splenic embolization (5), lumbar artery embolization (1), bronchial artery embolization (1), profunda artery embolization (1), common carotid artery stent (1), celiac artery stent (1), inferior vena cava filter placement (14) and retrieval (2), and pharmacomechanical thrombolysis (1). Treatment material included coils (12), Gelfoam (4), and nitinol plugs (3). No procedural or device-related complications occurred. Mortality was 14.7% unrelated to any endovascular procedure. One patient had repeat coil embolization of a pelvic pseudoaneurysm on postoperative Day 7. CONCLUSION: ACSTEV can safely treat TVI with good success. We performed nearly 10 procedures per month underscoring the role of the ACSTEV for training and care of TVI in a high-volume trauma center. LEVEL OF EVIDENCE: Therapeutic study, level V. PMID- 26891155 TI - Determining the magnitude of surveillance bias in the assessment of lower extremity deep venous thrombosis: A prospective observational study of two centers. AB - BACKGROUND: Venous thromboembolism (VTE) remains a significant cause of morbidity and mortality in trauma. Controversy exists regarding the use of lower extremity duplex ultrasound screening and surveillance (LEDUS). Advocates cite earlier diagnosis and treatment of deep venous thrombosis (DVT) to prevent clot propagation and pulmonary embolism (PE). Opponents argue that LEDUS identifies more DVT (surveillance bias) but does not reduce the incidence of PE. We sought to determine the magnitude of surveillance bias associated with LEDUS and test the hypothesis that LEDUS does not decrease the incidence of PE after injury. METHODS: We compared data from two Level 1 trauma centers: Scripps Mercy Hospital, which used serial LEDUS, and Christiana Care Health System, which used LEDUS only for symptomatic patients. Beginning in 2013, both centers prospectively collected data on demographics, injury severity, and VTE risk for patients admitted for more than 48 hours. Both centers used mechanical and pharmacologic prophylaxis based on VTE risk assessment. RESULTS: Scripps Mercy treated 772 patients and Christiana Care treated 454 patients with similar injury severity and VTE risk. The incidence of PE was 0.4% at both centers. The odds of a DVT diagnosis were 5.3 times higher (odds ratio, 5.3; 95% confidence interval, 2.5-12.9; p < 0.0001) for patients admitted to Scripps Mercy than for patients admitted to Christiana Care. Of the 80 patients who developed DVT, PE, or both, 99% received prophylaxis before the event. Among those who received pharmacologic prophylaxis, the VTE rates between the two centers were not statistically significantly different (Scripps Mercy, 11% vs. Christiana Care, 3%; p = 0.06). CONCLUSION: The odds of a diagnosis of DVT are increased significantly when a program of LEDUS is used in trauma patients. Neither pharmacologic prophylaxis nor mechanical prophylaxis is completely effective in preventing VTE in trauma patients. VTE should not be considered a "never event" in this cohort. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III; therapeutic study, level III. PMID- 26891156 TI - Randomized controlled trial comparing dynamic simulation with static simulation in trauma. AB - BACKGROUND: Current general surgery residents have limited exposure to open trauma operative cases. Simulation supplements variable rotation volume and provides experience with critical but rarely performed procedures. Open simulation classically focuses on static models with anatomic accuracy but lacks practicality when hemorrhage control is the lifesaving maneuver. We sought to evaluate whether training on a dynamic simulator, while much less expensive than training on a static cadaver, might be at least as effective in training surgery residents to expeditiously place temporary vascular shunts (TVSs). METHODS: Our research team developed an inexpensive, reusable dynamic simulator with ongoing hemorrhage to instruct trainees in the steps of TVS placement. We enrolled 54 general surgery residents in a noninferiority randomized controlled trial comparing training of TVS placement on the dynamic simulator (n = 28) versus a cadaver arm (n = 26). After standardized video didactics, trainees practiced on either the simulator or cadaver arm. After the trainees achieved competency, they were tested on placing a TVS for a live swine femoral artery injury. Two blinded trauma surgeons evaluated the recorded performances. RESULTS: Residents did not differ in baseline characteristics between groups, and all residents in both groups successfully completed the TVS placement test. Subjects trained on the simulator placed the TVS faster than those trained on a cadaver (584 seconds vs. 751 seconds; difference, +167 seconds faster; 90% confidence interval [CI], +52 to +282 seconds), with a trend toward faster time to hemorrhage control (110 seconds vs. 148 seconds; difference, +38 seconds faster; 90% CI, -8 to +84). There was no significant difference in Objective Structured Assessment of Technical Skills scores (3.72 vs. 3.44; difference, +0.27 units better; 90% CI, 0.04 to +0.59). CONCLUSION: Training on a dynamic simulator resulted in noninferior time to completion of vascular shunt placement compared with training on a cadaver. The addition of dynamic hemorrhage to simulators might inexpensively augment trauma skills training. PMID- 26891157 TI - Extracorporeal liver support for trauma-induced hepatic dysfunction. PMID- 26891158 TI - Feasibility of a perfused and ventilated cadaveric model for assessment of lifesaving traumatic hemorrhage and airway management skills. AB - BACKGROUND: Training health care providers to manage common life-threatening traumatic injuries is an important endeavor. A fresh perfused cadaveric model with high anatomic and tissue fidelity was developed to assess performance of hemorrhage and airway management skills during a simulated polytrauma scenario. METHODS: Fresh human cadavers were obtained within 96 hours of death. Hemorrhage from a right traumatic amputation and left inguinal wound was simulated using cannulation of the right popliteal and left femoral artery, respectively. The thoracic aorta (thoracotomy method) or external iliac arteries (Pfannenstiel method) were used for catheter access points. Lung ventilation to simulate chest rise and fall was achieved using bilateral chest tubes connected to a bag valve mask. Participants underwent a simulated nighttime field care scenario in which they attempted tourniquet placement, direct wound pressure and packing, and endotracheal intubation. RESULTS: Twenty-four donors were obtained (58-95 years old; mean, 77). There were 305 total scenarios completed using 23 cadavers (mean, approximately 13 scenarios per cadaver). The cost for acquisition and preparation of donors can be estimated at $3,611 to $9,399. CONCLUSION: This model successfully allowed for the demonstration of hemorrhage and airway management skills with high anatomic and tissue fidelity. For the assessment of critical lifesaving skills that are nondestructive in nature, the use of a fresh perfused cadaveric model is feasible and suitable for evaluation of these procedures. PMID- 26891159 TI - Acute care surgery and emergency general surgery: Addition by subtraction. AB - INTRODUCTION: The formation of Acute Care Surgery services leads to decreased time to treatment and improved outcomes for emergency general surgery (EGS) patients. However, minimal work has focused on the ideal care delivery system and team structure. We hypothesize that the implementation of a dedicated EGS team (separate from trauma and surgical critical care), with EGS-specific protocols and dedicated operating room (OR) time, will increase productivity and improve mortality. METHODS: This is a retrospective review of financial and EGS registry data from fiscal year (FY) 12 to FY15. Data are from an academic, university based EGS team composed of two acute care surgery attending surgeons, advanced practitioners (APs), residents, and a fellow. In FY12, processes were implemented to standardize paging of consults, patient sign-out with attending surgeons' and APs' participation, clinical/billing protocols, OR availability, and quality improvement. Outcomes included relative value units (RVUs), surgical case volume, charges/payments, and number of patient encounters. The secondary outcome was mortality. The chi test was used to compare mortality, and p < 0.05 was considered significant. RESULTS: Total patient encounters increased from 6,723 in FY 12 to 9,238 in FY 15 (+37%). Relative value units increased from 18,422 in FY 12 to 25,314 in FY 15 (+37%). Charges increased by 76% and payments increased by 60% from FY 12 to FY 15. Charges per encounter increased from $461 in FY 12 to $591 in FY 15 (+28%) Additionally, both inpatient and surgical case loads increased. Mortality remained stable throughout the study period (FY 12, 4.5%; FY 13, 5.2%; FY 14, 5.3%; FY 15, 3.2%: p = 0.177). CONCLUSIONS: Implementation of dedicated OR time, defined EGS team structure, practice protocols, and active attending surgeons'/APs' participation was temporally related to increased case volume, patients seen, and revenue, while mortality remained unchanged. Further study is necessary to establish the translatability of these data to other systems. LEVEL OF EVIDENCE: Economic/decision, level III. PMID- 26891160 TI - Infected hardware after surgical stabilization of rib fractures: Outcomes and management experience. AB - BACKGROUND: Surgical stabilization of rib fracture (SSRF) is increasingly used for treatment of rib fractures. There are few data on the incidence, risk factors, outcomes, and optimal management strategy for hardware infection in these patients. We aimed to develop and propose a management algorithm to help others treat this potentially morbid complication. METHODS: We retrospectively searched a prospectively collected rib fracture database for the records of all patients who underwent SSRF from August 2009 through March 2014 at our institution. We then analyzed for the subsequent development of hardware infection among these patients. Standard descriptive analyses were performed. RESULTS: Among 122 patients who underwent SSRF, most (73%) were men; the mean (SD) age was 59.5 (16.4) years, and median (interquartile range [IQR]) Injury Severity Score was 17 (13-22). The median number of rib fractures was 7 (5-9) and 48% of the patients had flail chest. Mortality at 30 days was 0.8%. Five patients (4.1%) had a hardware infection on mean (SD) postoperative day 12.0 (6.6). Median Injury Severity Score (17 [range, 13-42]) and hospital length of stay (9 days [6 37 days]) in these patients were similar to the values for those without infection (17 days [range, 13-22 days] and 9 days [6-12 days], respectively). Patients with infection underwent a median (IQR) of 2 (range, 2-3) additional operations, which included wound debridement (n = 5), negative-pressure wound therapy (n = 3), and antibiotic beads (n = 4). Hardware was removed in 3 patients at 140, 190, and 192 days after index operation. Cultures grew only gram-positive organisms. No patients required reintervention after hardware removal, and all achieved bony union and were taking no narcotics or antibiotics at the latest follow-up. CONCLUSIONS: Although uncommon, hardware infection after SSRF carries considerable morbidity. With the use of an aggressive multimodal management strategy, however, bony union and favorable long-term outcomes can be achieved. LEVEL OF EVIDENCE: Therapeutic study, level V. PMID- 26891161 TI - Timing of pulmonary embolisms in femur fracture patients: Incidence and outcomes. AB - BACKGROUND: Femur fracture is a well-recognized risk factor for pulmonary embolism (PE). Despite recent reports of early PE after major trauma, the incidence and outcomes of PE in femur fracture patients are unknown. The aims of the study were to determine the incidence of PE after a femur fracture and to evaluate its timing and clinical significance. METHODS: We included all consecutive adult patients (>=18 years old) with femur fracture admitted to our emergency department from January 2010 to December 2014 who underwent subsequent PE computed tomography within 72 hours. Of 453 stable patients, 28 with a confirmed diagnosis of acute PE were compared against those without PE. RESULTS: Of 1,301 femur fracture patients who presented at our hospital, 453 were included in our present analysis, of whom 28 developed PE (2.2%). Proximal PE, defined as emboli located within the main or lobar arteries, constituted 78.6% and subsegmental PE constituted 21.4% of these 28 cases. The femur fracture sites were mainly intertrochanteric (50.3%) and the neck (43.9%). The median interval from injury to computed tomography was 13.0 hours (IQR, 9.0-24.0 hours). PE was detected in 57.1% (16 of 28) of patients in the first 24 hours after injury and in 89.3% (25 of 28) in the first 48 hours. Overall mortality was 0.7%, and no patient in the early PE group died of their injury. CONCLUSION: PE arises in femur fracture patients in the immediate period following injury and shows an incidence somewhat higher than commonly appreciated in other trauma events but is not fatal. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III. PMID- 26891162 TI - Exogenous S-nitrosoglutathione attenuates inflammatory response and intestinal epithelial barrier injury in endotoxemic rats. AB - BACKGROUND: Gut barrier injury in sepsis is a major contributor to distant organ dysfunction and bad clinical outcomes. Enteric glia-derived S-nitrosoglutathione (GSNO) has been recognized as a novel modulator of gut barrier integrity. In this study, we tested the potential therapeutic effect and mechanism of exogenous GSNO on endotoxin-induced inflammatory response and intestinal barrier injury in a rat model of endotoxemia. METHODS: Male Sprague-Dawley rats were randomly assigned to four groups as follows: control (saline only), GSNO, lipopolysaccharide (LPS), and LPS + GSNO. Femoral venous injection of LPS (10 mg/kg) or saline was followed by GSNO (1 mg/kg) or saline injection 15 minutes later. Distal ileum tissues and blood were harvested after 3 hours of LPS/saline injection. The intestinal barrier function was measured histologically and by intestinal permeability to fluorescein isothiocyanate dextran. The ultrastructural change of the epithelial tight junction was observed using transmission electron microscope, and the expression level of tight junction protein ZO-1 was analyzed using immunofluorescence and Western blot. Systemic and intestinal inflammation was measured by analyzing the tumor necrosis factor and interleukin 1beta levels in plasma and distal ileum tissue, respectively. The levels of nuclear factor kappaB (NF-kappaB) and myosin light-chain kinase in the distal ileum were measured by Western blot. RESULTS: Compared with the endotoxemic rats, the addition of GSNO reduced the intestinal injury observed in histologic sections, decreased permeability to fluorescein isothiocyanate dextran, attenuated damage of the junction between epithelia, and protected against the LPS-induced expression decrease of ZO-1. Furthermore, addition of GSNO reduced plasma and intestinal tumor necrosis factor and interleukin 1beta levels as well as inhibited the LPS induced up-regulation of myosin light-chain kinase expression and NF-kappaB p65 level in the intestine. CONCLUSION: The data indicate that GSNO protects against the LPS-induced systemic inflammatory response and attenuated intestinal inflammation and epithelial barrier injury in rats, possibly through the inhibition of the NF-kappaB pathway. PMID- 26891164 TI - General route for the decomposition of InAs quantum dots during the capping process. AB - The effect of the capping process on the morphology of InAs/GaAs quantum dots (QDs) by using different GaAs-based capping layers (CLs), ranging from strain reduction layers to strain compensating layers, has been studied by transmission microscopic techniques. For this, we have measured simultaneously the height and diameter in buried and uncapped QDs covering populations of hundreds of QDs that are statistically reliable. First, the uncapped QD population evolves in all cases from a pyramidal shape into a more homogenous distribution of buried QDs with a spherical-dome shape, despite the different mechanisms implicated in the QD capping. Second, the shape of the buried QDs depends only on the final QD size, where the radius of curvature is function of the base diameter independently of the CL composition and growth conditions. An asymmetric evolution of the QDs' morphology takes place, in which the QD height and base diameter are modified in the amount required to adopt a similar stable shape characterized by a averaged aspect ratio of 0.21. Our results contradict the traditional model of QD material redistribution from the apex to the base and point to a different universal behavior of the overgrowth processes in self organized InAs QDs. PMID- 26891163 TI - A Mathematical Model Coupling Tumor Growth and Angiogenesis. AB - We present a mathematical model for vascular tumor growth. We use phase fields to model cellular growth and reaction-diffusion equations for the dynamics of angiogenic factors and nutrients. The model naturally predicts the shift from avascular to vascular growth at realistic scales. Our computations indicate that the negative regulation of the Delta-like ligand 4 signaling pathway slows down tumor growth by producing a larger density of non-functional capillaries. Our results show good quantitative agreement with experiments. PMID- 26891165 TI - Efficient Thermal-Light Interconversions Based on Optical Topological Transition in the Metal-Dielectric Multilayered Metamaterials. AB - Metal-dielectric multilayered metamaterials are proposed to work as wideband spectral-selective emitters/absorbers due to the topological change in isofrequency contour around the epsilon-near-zero point. By setting the transition at the border between the visible and IR ranges, the metal-dielectric multilayered metamaterials become good absorbers/emitters for visible light and good reflectors for IR light, which are desirable for efficient thermal-light interconversions. PMID- 26891166 TI - American College of Sports Medicine Joint Position Statement. Nutrition and Athletic Performance. AB - It is the position of the Academy of Nutrition and Dietetics, Dietitians of Canada, and the American College of Sports Medicine that the performance of, and recovery from, sporting activities are enhanced by well-chosen nutrition strategies. These organizations provide guidelines for the appropriate type, amount, and timing of intake of food, fluids, and supplements to promote optimal health and performance across different scenarios of training and competitive sport. This position paper was prepared for members of the Academy of Nutrition and Dietetics, Dietitians of Canada (DC), and American College of Sports Medicine (ACSM), other professional associations, government agencies, industry, and the public. It outlines the Academy's, DC's and ACSM's stance on nutrition factors that have been determined to influence athletic performance and emerging trends in the field of sports nutrition. Athletes should be referred to a registered dietitian/nutritionist for a personalized nutrition plan. In the United States and in Canada, the Certified Specialist in Sports Dietetics (CSSD) is a registered dietitian/nutritionist and a credentialed sports nutrition expert. PMID- 26891167 TI - LiAlH4 -Induced Selective Ring Rearrangement of 2-(2-Cyanoethyl)aziridines toward 2-(Aminomethyl)pyrrolidines and 3-Aminopiperidines as Eligible Heterocyclic Building Blocks. AB - 2-(2-Cyanoethyl)aziridines and 2-aryl-3-(2-cyanoethyl)aziridines were deployed as substrates for an In(OTf)3 -mediated regio- and stereoselective ring rearrangement upon treatment with LiAlH4, affording a variety of novel 2 (aminomethyl)pyrrolidines and 3-aminopiperidines, respectively. Further synthetic elaboration of the obtained 3-aminopiperidines resulted in the formation of a peculiar and unexplored conformationally constrained imidazolidinone and diketopiperazine scaffold. PMID- 26891169 TI - Do We Need Basic Research in Cardiac Surgery? AB - Thinking about the daily practice of cardiac surgery, genetically altered mouse models, polymerase chain reactions, western blots, and other laboratory tools are the last that comes to mind. It is, therefore, not surprising that the pursuit of such basic science activities by practicing surgeons and those in training is often limited. However, there is an innate connection between these two seemingly different disciplines. To address and visualize this connection, we propose the following three hypotheses. First, cardiac surgery would not be at its present level of expertise without fundamental contributions of basic science. Second, without practicing cardiac surgeons performing basic research and translating their results to clinical practice next to their daily work, our ability to care for cardiac surgery patients would be poorer. Third, basic science training for those aiming to become practicing cardiac surgeons improves their ability to properly care for their patients. Finally, we will discuss some potentially even unexpected implications for our currently changing daily clinical practice. PMID- 26891168 TI - Endovascular Repair of Paravisceral Aortic Aneurysms Combining Chimney Grafts and the Nellix Endovascular Aneurysm Sealing Technology (Four-Vessel ChEVAS). AB - Background We demonstrate our initial experience and first results of the endovascular aneurysm sealing (EVAS) technology with chimney grafts for the treatment of paravisceral aneurysms. Methods We present a consecutive series of seven patients with a mean age of 75 years who had been treated by four-vessel chimney EVAS (ChEVAS) between May 2014 and May 2015. All patients were ASA grade >= III and were not eligible for fenestrated/branched endovascular aortic repair (fEVAR/brEVAR) due to urgency (n = 5) or anatomical constraints (n = 2). Results Total 28 renovisceral target vessels were treated by balloon-expandable covered stents and 14 Nellix devices were used to seal the paravisceral aorta. Overall, 16 Nellix (Endologix Inc., Irvine, California, United States) devices and 65 covered stents were implanted with a technical success of 100%. Perioperatively, one patient with ruptured aneurysm died due to respiratory failure following splenic laceration/splenectomy (mortality = 14%) and in one patient, laceration of an axillary access vessel occurred. At a median follow-up of 6 months, all six surviving patients were well and no reinterventions were necessary. One chimney was found occluded without clinical sequelae resulting in a patency rate of 96%. Conclusion Four-vessel ChEVAS may serve as alternative treatment option in highly selected cases of either acute paravisceral aortic pathology and/or situations, where the implantation of fEVAR/brEVAR is hampered by anatomical constraints. Further follow-up and a multicenter study are of course warranted to corroborate these initial results. PMID- 26891170 TI - High-resolution manometry in patients with eosinophilic esophagitis under topical steroid therapy-a prospective observational study (HIMEOS-study). AB - BACKGROUND: In eosinophilic esophagitis (EoE), dysphagia, which might reflect esophageal dysmotility, is the most common symptom. High-resolution manometry (HRM) has become widely accepted for evaluating esophageal motility disorders, but to date has been sparsely examined in EoE patients, particularly under therapy. The aim of this study was to evaluate HRM in symptomatic EoE-patients under topical steroid treatment. METHODS: In this prospective observational study, symptomatic EoE patients received HRM-examinations before and after 8 weeks of topical steroid treatment with budesonide. All HRM-abnormalities were assessed and interpreted according to the Chicago classification. The primary endpoint was the influence of topical steroid treatment on the intrabolus pressure (IBP). Clinical symptoms, endoscopic findings and histological esophageal eosinophilic load were also reported. KEY RESULTS: Twenty symptomatic EoE patients were included. Overall success of budesonide therapy was 85% regarding complete histologic remission and 80% regarding complete clinical remission. High-resolution manometry showed abnormal esophageal motility in 35% of patients at baseline, which was resolved after therapy in 86% of these patients. Most frequent HRM-findings were early pan-esophageal pressurizations and weak persitalsis. There was no significant reduction of the IBP under therapy (before: 12.5 +/- 4.9 mmHg, after: 10.9 +/- 2.9 mmHg; p = 0.119). CONCLUSIONS & INFERENCES: Although dysphagia is the leading symptom of EoE, HRM is able to identify esophageal motility disorders in only some EoE patients. Observed motility disorders resolve after successful treatment in almost all of these patients. Intrabolus pressure does not seem an optimal parameter for the monitoring of successful treatment response in EoE patients. PMID- 26891171 TI - Multi-scale finite element modeling of Eustachian tube function: influence of mucosal adhesion. AB - The inability to open the collapsible Eustachian tube (ET) leads to the development of chronic Otitis Media (OM). Although mucosal inflammation during OM leads to increased mucin gene expression and elevated adhesion forces within the ET lumen, it is not known how changes in mucosal adhesion alter the biomechanical mechanisms of ET function. In this study, we developed a novel multi-scale finite element model of ET function in adults that utilizes adhesion spring elements to simulate changes in mucosal adhesion. Models were created for six adult subjects, and dynamic patterns in muscle contraction were used to simulate the wave-like opening of the ET that occurs during swallowing. Results indicate that ET opening is highly sensitive to the level of mucosal adhesion and that exceeding a critical value of adhesion leads to rapid ET dysfunction. Parameter variation studies and sensitivity analysis indicate that increased mucosal adhesion alters the relative importance of several tissue biomechanical properties. For example, increases in mucosal adhesion reduced the sensitivity of ET function to tensor veli palatini muscle forces but did not alter the insensitivity of ET function to levator veli palatini muscle forces. Interestingly, although changes in cartilage stiffness did not significantly influence ET opening under low adhesion conditions, ET opening was highly sensitive to changes in cartilage stiffness under high adhesion conditions. Therefore, our multi-scale computational models indicate that changes in mucosal adhesion as would occur during inflammatory OM alter the biomechanical mechanisms of ET function. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891173 TI - Bottom-up electrochemical preparation of solid-state carbon nanodots directly from nitriles/ionic liquids using carbon-free electrodes and the applications in specific ferric ion detection and cell imaging. AB - Carbon nanodots (C-dots), a new type of potential alternative to conventional semiconductor quantum dots, have attracted numerous attentions in various applications including bio-chemical sensing, cell imaging, etc., due to their chemical inertness, low toxicity and flexible functionalization. Various methods including electrochemical (EC) methods have been reported for the synthesis of C dots. However, complex procedures and/or carbon source-containing electrodes are often required. Herein, solid-state C-dots were simply prepared by bottom-up EC carbonization of nitriles (e.g. acetonitrile) in the presence of an ionic liquid [e.g. 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6)], using carbon free electrodes. Due to the positive charges of BMIM(+) on the C-dots, the final products presented in a precipitate form on the cathode, and the unreacted nitriles and BMIMPF6 can be easily removed by simple vacuum filtration. The as prepared solid-state C-dots can be well dispersed in an aqueous medium with excellent photoluminescence properties. The average size of the C-dots was found to be 3.02 +/- 0.12 nm as evidenced by transmission electron microscopy. Other techniques such as UV-vis spectroscopy, fluorescence spectroscopy, X-ray photoelectron spectroscopy and atomic force microscopy were applied for the characterization of the C-dots and to analyze the possible generation mechanism. These C-dots have been successfully applied in efficient cell imaging and specific ferric ion detection. PMID- 26891172 TI - Combined IL-12 Plasmid and Recombinant SjGST Enhance the Protective and Anti pathology Effect of SjGST DNA Vaccine Against Schistosoma japonicum. AB - Schistosomiasis is listed as one of most important tropical diseases and more than 200 million people are estimated to be infected. Development of a vaccine is thought to be the most effective way to control this disease. Recombinant 26-kDa glutathione S-transferase (rSjGST) has previously been reported to achieve a worm reduction rate of 42-44%. To improve the efficiency of the vaccine against Schistosoma japonicum, we immunized mice with a combination of pcDNA vector encoded 26-kDa SjGST (pcDNA/SjGST), IL-12 expressing-plasmid (pIL-12), and rSjGST. Co-vaccination with pcDNA/SjGST, pIL-12, and rSjGST led to a reduction in worm burden, hepatic egg burden, and the size of liver tissue granulomas than that in the untreated infection controls. In addition, we detected high levels of specific IgG, IgG1, and IgG2a against the rSjGST antigen in infected mice vaccinated with this combination of pcDNA/SjGST, pIL-12, and rSjGST. Moreover, high expression levels of Th2 cytokines, including IL-4 and IL-10, were also detected in this group, without diminished levels of IL-12, INF-gamma, and TNF alpha cytokines that are related to parasite killing. In conclusion, we have developed a new vaccination regimen against S. japonicum infection and shown that co-immunization with pcDNA/SjGST vaccine, pIL-12, and rSjGST has significant anti parasite, anti-hepatic egg and anti-pathology effects in mice. The efficacy of this vaccination method should be further validated in large animals such as water buffalo. This method may help to reduce the transmission of zoonotic schistosomiasis japonica. PMID- 26891174 TI - Potentiating Cancer Immunotherapy Using Papaya Mosaic Virus-Derived Nanoparticles. AB - The recent development of novel immunotherapies is revolutionizing cancer treatment. These include, for example, immune checkpoint blockade, immunomodulation, or therapeutic vaccination. Although effective on their own, combining multiple approaches will most likely be required in order to achieve the maximal therapeutic benefit. In this regard, the papaya mosaic virus nanoparticle (PapMV) has shown tremendous potential as (i) an immunostimulatory molecule, (ii) an adjuvant, and (iii) a vaccine platform through its intrinsic capacity to activate the innate immune response in an IFN-alpha-dependent manner. Here, we demonstrate that intratumor administration of PapMV significantly slows down melanoma progression and prolongs survival. This correlates with enhanced chemokine and pro-inflammatory-cytokine production in the tumor and increased immune-cell infiltration. Proportions of total and tumor-specific CD8(+) T cells dramatically increase following PapMV treatment whereas those of myeloid-derived suppressor cells (MDSC) concomitantly decrease. Moreover, systemic PapMV administration prevents metastatic tumor-implantation in the lungs. Importantly, PapMV also synergistically improves the therapeutic benefit of dendritic cell (DC)-based vaccination and PD-1 blockade by potentiating antitumor immune responses. This study illustrates the immunostimulatory potential of a plant virus-derived nanoparticle for cancer therapy either alone or in conjunction with other promising immunotherapies in clinical development. PMID- 26891177 TI - Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies. AB - We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA. PMID- 26891175 TI - NSCLC harboring EGFR exon-20 insertions after the regulatory C-helix of kinase domain responds poorly to known EGFR inhibitors. AB - Anecdote clinical observations hint that non-small cell lung cancer (NSCLC) with exon-20 insertions might respond poorly to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), contrasting to those with classic mutations. Lack of patient-derived experimental models has been a major hurdle for the discovery of new treatment for the diseases. We established two NSCLC PDXs harboring two different exon-20 insertions, LU0387-adenocarcinoma (ADC) with a nine-base insertion at 2319 (H773-V774insNPH) and LU3075-squamous cell carcinoma (SCC) with a nine-base insertion at 2316 (P772-H773insDNP). Both insertions immediately follow the regulatory C-helix of the kinase domain. Contrary to the generally good responses to EGFR inhibitors observed in PDXs with classic mutations, both exon-20 insertions are largely resistant to cetuximab and TKIs in vivo, suggesting fundamental difference from the classic EGFR mutations, consistent with the poor response rate to TKI seen in anecdotal clinic reports. It is worth noting that although responses are generally poor, they differ between the two exon-20 mutants depending on the type of TKI. In vitro drug sensitivity assays using established primary cell lines from our two PDXs largely confirmed the in vivo data. Our data from patient-derived experimental models confirmed that exon-20 insertions in domain immediately following the C-helix confer poor response to all known EGFR inhibitors, and suggested that these models can be utilized to facilitate the discovery of new therapies targeting NSCLC harboring exon-20 insertions. PMID- 26891176 TI - Multimodal Swallowing Evaluation with High-Resolution Manometry Reveals Subtle Swallowing Changes in Early and Mid-Stage Parkinson Disease. AB - BACKGROUND: Parkinson disease (PD) has detrimental effects on swallowing function. Treatment options are largely behavioral; thus, patients would benefit from an earlier start to therapy. Early swallowing changes in PD are not well known, so patients do not typically receive swallowing treatment until later in the progression of PD. OBJECTIVE: We used predictive modeling to determine what quantitative swallowing variables best differentiate individuals with early to mid-stage PD from healthy controls. METHODS: Participants included twenty-six individuals with early to mid-stage PD and 26 healthy, age- and sex-matched controls. Swallowing was evaluated by simultaneous high-resolution manometry and videofluoroscopy as well as the Sydney Swallow Questionnaire (SSQ). Binomial logistic regression was performed on 4 sets of data: 1) high-resolution manometry only; 2) videofluoroscopy only; 3) SSQ only; and 4) all data combined. RESULTS: A model from a combined data set had the highest accuracy in differentiating individuals with PD from controls. The model included maximum pressure in the velopharynx (soft palate), pressure variability in the velopharynx, and the SSQ item concerning difficulty with swallowing saliva. No significant models could be generated using the videofluoroscopy data. CONCLUSIONS: Individuals with PD show quantitative changes in pressure generation and are able to self-assess aspects of swallowing function in the early and mid-stages of PD, even in the absence of swallowing changes seen on videofluoroscopy. A multimodal approach for the assessment of swallowing may be more accurate for determining subtle swallowing changes that occur in the early stages of PD. PMID- 26891178 TI - Unusual case of traumatic neuroma of the orbit. AB - Traumatic or amputation neuromas are neoformations developing after damage to a peripheral nerve. They are not proper tumors but rather a reactive process or a frustrated attempt of nerve regeneration. Traumatic neuromas are potentially found in every sensory peripheral nerve and often at the site of past surgical intervention, including orbital surgery. A 29-year-old Northern African migrant presented progressive exophthalmos and progressive loss of acuity in left eye, which had started about 6 months before after a cranio-facial trauma caused by a violent assault. MRI of the orbits showed a massive intra-orbital, intra-conical lesion, clearly compressing and dislocating the optic nerve and extending posteriorly to the orbital apex. Surgery was performed through lateral approach of Kroenlein and led to complete excision of the lesion. Histology revealed fibrotic, adipose and striated muscle tissues, a disordered, non-neoplastic overgrowth of small and large fascicles of nerves, inflammatory infiltrates, and fibrosis with sparse calcifications were diffusely observed in a background of fat, scar and striated muscle tissued. Patient was discharged on the fifth day in good health condition, without deficit of eye motion but without recovery of visual acuity. In conclusion, this case demonstrates that traumatic neuromas may arise in the orbit in patients with minor direct trauma to nerves and without previous surgical treatment. PMID- 26891180 TI - Fatty acid binding protein 3 is associated with skeletal muscle strength in polymyositis and dermatomyositis. AB - OBJECTIVE: To determine serum levels and histopathological characteristics of fatty acid binding protein 3 (FABP3) in patients with polymyositis (PM) and dermatomyositis (DM), and to evaluate the correlation between the FABP3 and muscle strength. METHODS: The study population included 24 subjects with PM/DM, 12 subjects with asymptomatic or minimally symptomatic hyper-creatine kinase-emia (AMSH), and 10 healthy control subjects. Muscle strength was measured by using the Manual Muscle Test (MMT8). Serum CK, myoglobin and FABP3 levels were tested. Correlations between variables were studied by using Spearman's rank and partial correlation analysis methods. Immunohistochemical and double immunofluorescent stainings of FABP3 were performed to investigate its distribution in skeletal muscle. RESULTS: PM/DM patients had significantly higher (P < 0.05) serum FABP3 levels (35.46 +/- 38.45 ng/mL) than did AMSH patients (3.77 +/- 1.21 ng/mL) and healthy control subjects (4.30 +/- 3.18 ng/mL). MMT8 scores correlated negatively with CK, myoglobin and FABP3 levels. Partial correlation analysis was performed and showed that the correlation coefficients between MMT8 score and serum CK, myoglobin and FABP3 levels were -0.276 (P > 0.05), -0.228 (P > 0.05) and -0.927 (P < 0.001), respectively. Immunohistochemical and double immunofluorescent staining showed that FABP3 expression increased in the skeletal muscle of PM/DM patients and was mainly distributed in slow twitch muscle fibers. CONCLUSION: Serum levels of FABP3 in PM/DM patients were significantly increased and were mainly distributed in slow twitch muscle fibers, displaying a closer association with muscle weakness than did serum levels of CK and myoglobin. FABP3 is likely to be a useful serum biomarker in PM/DM patients. PMID- 26891181 TI - Balancing risk and benefit in heavy drinkers treated with topiramate: implications for personalized care. AB - BACKGROUND: Despite topiramate's ability to reduce heavy drinking, its adverse effects may limit its clinical utility. METHOD: To evaluate the risks and benefits of topiramate, we reanalyzed data from a completed trial of the medication in 138 heavy drinkers whose goal was to reduce their drinking to safe levels. We used the number of patients who had no heavy drinking days during the last 4 weeks of treatment to calculate topiramate's number needed to treat (NNT). To balance the risks and benefits of topiramate, we adjusted the NNT using 2 different levels of adverse event severity: moderate or greater (NNT-AEmod+) and severe or greater (NNT-AEsev+). This measure helps to guide the clinical use of topiramate in heavy drinkers by incorporating both its beneficial and adverse effects in a single measure. Because a polymorphism (rs2832407) in the gene encoding a kainate receptor subunit appears to moderate topiramate's effects in heavy drinkers, we repeated the analyses based on rs2832407 genotype (C homozygote vs A-allele carrier) in the European American subsample (n = 122). RESULTS: Overall, the NNT for topiramate was 5.29, the NNT-AEmod+ was 7.52, and the NNT-AEsev+ was 6.12. Among European Americans with the rs2832407*CC genotype, the NNT was 2.28, the NNT-AEmod+ was 2.63, and the NNT-AEsev+ was 2.56. In contrast, for rs2832407*A-allele carriers, the NNT was 180.00, the NNT-AEmod+ was 322.16, and the NNT-AEsev+ was 217.45. CONCLUSIONS: In this sample of heavy drinkers, topiramate had a clinically important treatment effect that was most evident in European Americans with the rs2832407*CC genotype. In that group, in particular, it had a robust treatment effect, even when adjusted for adverse events. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00626925. PMID- 26891179 TI - Interactome Mapping Reveals the Evolutionary History of the Nuclear Pore Complex. AB - The nuclear pore complex (NPC) is responsible for nucleocytoplasmic transport and constitutes a hub for control of gene expression. The components of NPCs from several eukaryotic lineages have been determined, but only the yeast and vertebrate NPCs have been extensively characterized at the quaternary level. Significantly, recent evidence indicates that compositional similarity does not necessarily correspond to homologous architecture between NPCs from different taxa. To address this, we describe the interactome of the trypanosome NPC, a representative, highly divergent eukaryote. We identify numerous new NPC components and report an exhaustive interactome, allowing assignment of trypanosome nucleoporins to discrete NPC substructures. Remarkably, despite retaining similar protein composition, there are exceptional architectural dissimilarities between opisthokont (yeast and vertebrates) and excavate (trypanosomes) NPCs. Whilst elements of the inner core are conserved, numerous peripheral structures are highly divergent, perhaps reflecting requirements to interface with divergent nuclear and cytoplasmic functions. Moreover, the trypanosome NPC has almost complete nucleocytoplasmic symmetry, in contrast to the opisthokont NPC; this may reflect divergence in RNA export processes at the NPC cytoplasmic face, as we find evidence supporting Ran-dependent mRNA export in trypanosomes, similar to protein transport. We propose a model of stepwise acquisition of nucleocytoplasmic mechanistic complexity and demonstrate that detailed dissection of macromolecular complexes provides fuller understanding of evolutionary processes. PMID- 26891183 TI - Conditional Survival and Predictors of Late Death in Patients With Ewing Sarcoma. AB - PURPOSE: Long-term survivors of Ewing sarcoma (EWS) are at considerable risk for future complications, including late relapse and death. Data on prognostic factors for late death in those who have survived beyond 5 years are lacking. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. We obtained clinical features and outcome data on 1,351 patients with EWS who had survived 60 months or more. From these data, we performed univariate and multivariable analyses of overall survival (OS) using log-rank tests and Cox proportional hazard models. RESULTS: Of 1,351 patients in the cohort, there were 209 deaths, 144 (69%) of which were reported to be due to EWS. The OS for 5-year survivors at 10 years was 87.5% (95% confidence interval 85.4-89.3%). Univariate adverse prognostic factors for late death in 5-year survivors included age >= 18 years at initial diagnosis, male sex, and axial/pelvic primary site. Initial stage was not prognostic. Independent adverse prognostic factors for late death included black race (hazard ratio [HR] 2.16, P = 0.01), age >= 18 years at diagnosis (HR 2.02, P < 0.001), male sex (HR 1.43, P = 0.01), and axial/pelvic primary site (HR 1.43, P = 0.02). CONCLUSIONS: The majority of late deaths in 5-year survivors are due to EWS. Black race, age >=18 at diagnosis, male sex, and axial/pelvic primary site (but not stage at diagnosis) are independently associated with increased risk of late death. PMID- 26891182 TI - Adeno-associated virus-delivered artificial microRNA extends survival and delays paralysis in an amyotrophic lateral sclerosis mouse model. AB - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of motor neurons, resulting in progressive muscle weakness, paralysis, and death within 5 years of diagnosis. About 10% of cases are inherited, of which 20% are due to mutations in the superoxide dismutase 1 (SOD1) gene. Riluzole, the only US Food and Drug Administration-approved ALS drug, prolongs survival by only a few months. Experiments in transgenic ALS mouse models have shown decreasing levels of mutant SOD1 protein as a potential therapeutic approach. We sought to develop an efficient adeno-associated virus (AAV)-mediated RNAi gene therapy for ALS. METHODS: A single-stranded AAV9 vector encoding an artificial microRNA against human SOD1 was injected into the cerebral lateral ventricles of neonatal SOD1(G93A) mice, and impact on disease progression and survival was assessed. RESULTS: This therapy extended median survival by 50% and delayed hindlimb paralysis, with animals remaining ambulatory until the humane endpoint, which was due to rapid body weight loss. AAV9-treated SOD1(G93A) mice showed reduction of mutant human SOD1 mRNA levels in upper and lower motor neurons and significant improvements in multiple parameters including the numbers of spinal motor neurons, diameter of ventral root axons, and extent of neuroinflammation in the SOD1(G93A) spinal cord. Mice also showed previously unexplored changes in pulmonary function, with AAV9-treated SOD1(G93A) mice displaying a phenotype reminiscent of patient pathophysiology. INTERPRETATION: These studies clearly demonstrate that an AAV9-delivered SOD1-specific artificial microRNA is an effective and translatable therapeutic approach for ALS. PMID- 26891185 TI - Patient Diagnostic Rate as Indicator of Tuberculosis Case Detection, South Africa. AB - To address the uncertainty of the indirectly measured tuberculosis case detection rate, we used survey data stratified by HIV status to calculate the patient diagnostic rate, a directly measurable indicator, in 8 communities in South Africa. Rates were lower among HIV-negative than HIV-positive persons. Tuberculosis programs should focus on HIV-negative persons. PMID- 26891184 TI - Status and characteristics of ambient PM2.5 pollution in global megacities. AB - Ambient PM2.5 pollution is a substantial threat to public health in global megacities. This paper reviews the PM2.5 pollution of 45 global megacities in 2013, based on mass concentration from official monitoring networks and composition data reported in the literature. The results showed that the five most polluted megacities were Delhi, Cairo, Xi'an, Tianjin and Chengdu, all of which had an annual average concentration of PM2.5 greater than 89MUg/m(3). The five cleanest megacities were Miami, Toronto, New York, Madrid and Philadelphia, the annual averages of which were less than 10MUg/m(3). Spatial distribution indicated that the highly polluted megacities are concentrated in east-central China and the Indo-Gangetic Plain. Organic matter and SNA (sum of sulfate, nitrate and ammonium) contributed 30% and 36%, respectively, of the average PM2.5 mass for all megacities. Notable seasonal variation of PM2.5 polluted days was observed, especially for the polluted megacities of China and India, resulting in frequent heavy pollution episodes occurring during more polluted seasons such as winter. Marked differences in PM2.5 pollution between developing and developed megacities require more effort on local emissions reduction as well as global cooperation to address the PM2.5 pollution of those megacities mainly in Asia. PMID- 26891186 TI - Repeatability of a dynamic rollover test system. AB - OBJECTIVE: The goal of this study was to characterize the rollover crash and to evaluate the repeatability of the Dynamic Rollover Test System (DRoTS) in terms of initial roof-to-ground contact conditions, vehicle kinematics, road reaction forces, and vehicle deformation. METHODS: Four rollover crash tests were performed on 2 pairs of replicate vehicles (2 sedan tests and 2 compact multipurpose van [MPV] tests), instrumented with a custom inertial measurement unit to measure vehicle and global kinematics and string potentiometers to measure pillar deformation time histories. The road was instrumented with load cells to measure reaction loads and an optical encoder to measure road velocity. Laser scans of pre- and posttest vehicles were taken to provide detailed deformation maps. RESULTS: Initial conditions were found to be repeatable, with the largest difference seen in drop height of 20 mm; roll rate, roll angle, pitch angle, road velocity, drop velocity, mass, and moment of inertia were all 7% different or less. Vehicle kinematics (roll rate, road speed, roll and pitch angle, global Z' acceleration, and global Z' velocity) were similar throughout the impact; however, differences were seen in the sedan tests because of a vehicle fixation problem and differences were seen in the MPV tests due to an increase in reaction forces during leading side impact likely caused by disparities in roll angle (3 degrees difference) and mass properties (2.2% in moment of inertia [MOI], 53.5 mm difference in center of gravity [CG] location). CONCLUSIONS: Despite those issues, kinetic and deformation measures showed a high degree of repeatability, which is necessary for assessing injury risk in rollover because roof strength positively correlates with injury risk (Brumbelow 2009). Improvements of the test equipment and matching mass properties will ensure highly repeatable initial conditions, vehicle kinematics, kinetics, and deformations. PMID- 26891187 TI - Introduction. PMID- 26891188 TI - Synthetic studies towards putative yuremamine using an iterative C(sp(3))-H arylation strategy. AB - An overview of an iterative, 8-aminoquinoline (AQ)-directed C(sp(3))-H arylation strategy towards the pyrroloindole structure initially assigned to the alkaloid yuremamine is described. During initial efforts using a model indane system, it was discovered that the iodoresorcinol unit was not a viable C(sp(3))-H arylation partner when masked as its dimethyl ether but upon switching to a MOM group, the ether oxygen served to stabilise the high valent Pd intermediate during the reaction, thus promoting reductive elimination and leading to acceptable yields of the C(sp(3))-H arylation product. The second C(sp(3))-H arylation with an iodopyrogallol gave a 1,3-diarylated model yuremamine system possessing the desired 1,3-cis relationship. When the successful model studies were applied to a pyrroloindole system in pursuit of yuremamine, it became apparent that C9 underwent competing C(sp(2))-H arylation if left vacant, but installing a tryptamine side chain at this site prevented the desired C(sp(3))-H arylation from occurring altogether. However, a C9-methyl pyrroloindole underwent iterative C(sp(3))-H arylation at C1 with an iodoresorcinol followed by C3 with an iodopyrogallol to give a diarylated product with the aryl groups in the undesired 1,3-trans-relationship, arising from epimerisation at C1 during the second C(sp(3))-H arylation event. Although the synthesis of putative yuremamine was not accomplished, several findings are disclosed that will serve as useful additions to the burgeoning field of directed C(sp(3))-H arylations and related C-H functionalization reactions. PMID- 26891189 TI - Interval estimation of small tail probabilities - applications in food safety. AB - Often in food safety and bio-surveillance it is desirable to estimate the probability that a contaminant or a function thereof exceeds an unsafe high threshold. The probability or chance in question is very small. To estimate such a probability, we need information about large values. In many cases, the data do not contain information about exceedingly large contamination levels, which ostensibly renders the problem insolvable. A solution is suggested whereby more information about small tail probabilities are obtained by combining the real data with computer-generated data repeatedly. This method provides short yet reliable interval estimates based on moderately large samples. An illustration is provided in terms of lead exposure data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891190 TI - The borderlands of waking: Quantifying the transition from reflective thought to hallucination in sleep onset. AB - We lose waking consciousness spontaneously and regularly over the circadian cycle. It seems that every time we fall asleep, reflective thinking gradually gives way to our interactions with an imaginary, hallucinatory world that brings multimodal experiences in the absence of adequate external stimuli. The present study investigates this transition, proposing a new measure of hallucinatory states. Reflective thinking and motor imagery were quantified in 150 mentation reports provided by 16 participants after forced awakenings from different physiology-monitored time intervals after sleep onset. Cognitive agency analysis and motor agency analysis--which are objective (grammatical-semantic) tools derived from linguistic theories--show (i) a decrease in reflective thinking which sleepers would need to acknowledge the hallucinatory quality of their state, and (ii) an increase in motor imagery, indicating interactions with a hallucinatory world. By mapping these spontaneous changes in human consciousness onto physiology, we can in the long run explore the conditions of its decline, and possibilities for treatment. PMID- 26891191 TI - Individuals with pronounced schizotypal traits are particularly successful in tickling themselves. AB - We assessed self-tickling sensations in a group of participants high in schizotypal traits (n=27) and group of participants low in schizotypal traits (n=27). The groups were formed by screening a pool of 397 students for extreme scores in the French version of the Schizotypal Personality Questionnaire. As observed in a previous study involving psychiatric people with auditory hallucinations and/or passivity experiences our results showed that self-applied tactile stimulations are felt to be more ticklish by healthy individuals high in schizotypal traits. In contrast, there were no significant intergroup differences in the mean tickle rating in the externally-produced tickling condition. Furthermore, more successful self-tickling was associated with more frequent self reports of unusual perceptual experiences (such as supernatural experiences) and passivity experiences in particular (such as a feeling of being under the control of an outside force or power). PMID- 26891192 TI - Occlusions at event boundaries during encoding have a negative effect on infant memory. AB - The present study investigated the importance of Event Boundaries for 16- and 20 month-olds' (n=80) memory for cartoons. The infants watched one out of two cartoons with ellipses inserted covering the screen for 3s either at Event Boundaries or at Non-Boundaries. After a two-week delay both cartoons (one familiar and one novel) were presented simultaneously without ellipses while eye tracking the infants. According to recent evidence a familiarity preference was expected. However, following Event Segmentation Theory ellipses at Event Boundaries were expected to cause greater disturbance of the encoding and hence a weaker memory trace evidenced by reduced familiarity preference, relative to ellipses at Non-Boundaries. The results suggest that overall this was the case, documenting the importance of Boundaries for infant memory. Furthermore, planned analyses revealed that whereas the same pattern was found when looking at the 20 month-old infants, no significant difference was found between the two conditions in the youngest age-group. PMID- 26891194 TI - Novel Fused Arylpyrimidinone Based Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor. AB - Benzoquinazolinone 1 is a positive allosteric modulator (PAM) of the M1 muscarinic acetylcholine receptor (mAChR), which is significantly more potent than the prototypical PAM, 1-(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3 carboxylic acid (BQCA). In this study, we explored the structural determinants that underlie the activity of 1 as a PAM of the M1 mAChR. We paid particular attention to the importance of the tricyclic scaffold of compound 1, for the activity of the molecule. Complete deletion of the peripheral fused benzene ring caused a significant decrease in affinity and binding cooperativity with acetylcholine (ACh). This loss of affinity was rescued with the addition of either one or two methyl groups in the 7- and/or 8-position of the quinazolin 4(3H)-one core. These results demonstrate that the tricyclic benzo[h]quinazolin 4(3H)-one core could be replaced with a quinazolin-4(3H)-one core and maintain functional affinity. As such, the quinazolin-4(3H)-one core represents a novel scaffold to further explore M1 mAChR PAMs with improved physicochemical properties. PMID- 26891195 TI - Patient and Provider-Identified Factors Contributing to Surgical Readmission After Colorectal Surgery. AB - PURPOSE: Nearly one in seven surgical patients is readmitted to the hospital within 30 days of discharge. Few studies have identified patient-centric factors that raise the risk of both preventable and nonpreventable postoperative readmissions. MATERIALS AND METHODS: Over 6 months in 2012, 48 colorectal surgical patients were identified on re-admission within 30 days of discharge. We prospectively obtained information on the patient's and primary surgeon's views on factors that contributed to readmission, and compiled data to produce an external list of contributing factors. A standard cost analysis was performed. RESULTS: 48 colorectal surgery patients participated, and 47 were included in this patient-centric evaluation of factors leading to readmission. The three primary readmission diagnoses included dehydration, fever, and ileus or small bowel obstruction. Of all readmissions, 23% were considered to be preventable. 38% of patients had scheduled follow-up appointments that were documented in the medical record at the time of discharge. Providers identified several factors contributing to readmission including difficulty understanding discharge plan, medication management and premature discharge. Per patient, the cost of preventable readmission was $15,366 (+/-20%; $12,293-$18,439). Total preventable cost was $169,025 (+/-20%; $135,220-$202,829). CONCLUSIONS: The ability to obtain an outpatient postoperative appointment and the understanding of their own postoperative care were the most commonly identified barriers. Interventions to help reduce unnecessary readmissions include a standard discharge process and coordinator, and routine (<7 days) postdischarge outpatient appointments. Successful reduction of preventable readmissions would result in approximately $3.6 million in cost savings per 1,000 colorectal readmissions. PMID- 26891193 TI - The physiological and clinical importance of sodium potassium ATPase in cardiovascular diseases. AB - The Na/K-ATPase has been extensively studied, but it is only recently that its role as a scaffolding and signaling protein has been identified. It has been identified that cardiotonic steroids (CTS) such as digitalis mediate signal transduction through the Na/K-ATPase in a process found to result in the generation of reactive oxygen species (ROS). As these ROS also appear capable of initiating this signal cascade, a feed forward amplification process has been postulated and subsequently implicated in some disease pathways including uremic cardiomyopathy. PMID- 26891196 TI - Calibration of high flow rate thoracic-size selective samplers. AB - High flow rate respirable size selective samplers, GK4.126 and FSP10 cyclones, were calibrated for thoracic-size selective sampling in two different laboratories. The National Institute for Occupational Safety and Health (NIOSH) utilized monodisperse ammonium fluorescein particles and scanning electron microscopy to determine the aerodynamic particle size of the monodisperse aerosol. Fluorescein intensity was measured to determine sampling efficiencies of the cyclones. The Health Safety and Laboratory (HSL) utilized a real time particle sizing instrument (Aerodynamic Particle Sizer) and polydisperse glass sphere particles and particle size distributions between the cyclone and reference sampler were compared. Sampling efficiency of the cyclones were compared to the thoracic convention defined by the American Conference of Governmental Industrial Hygienists (ACGIH)/Comite Europeen de Normalisation (CEN)/International Standards Organization (ISO). The GK4.126 cyclone showed minimum bias compared to the thoracic convention at flow rates of 3.5 l min(-1) (NIOSH) and 2.7-3.3 l min(-1) (HSL) and the difference may be from the use of different test systems. In order to collect the most dust and reduce the limit of detection, HSL suggested using the upper end in range (3.3 l min(-1)). A flow rate of 3.4 l min(-1) would be a reasonable compromise, pending confirmation in other laboratories. The FSP10 cyclone showed minimum bias at the flow rate of 4.0 l min(-1) in the NIOSH laboratory test. The high flow rate thoracic-size selective samplers might be used for higher sample mass collection in order to meet analytical limits of quantification. PMID- 26891198 TI - Outpatient treatment of uncomplicated diverticulitis: a systematic review. AB - Acute diverticulitis occurs in up to 25% of patients with diverticulosis. The majority of cases are mild or uncomplicated and it has become a frequent reason for consultation in the emergency department. On the basis of the National Inpatient Sample database from the USA, 86% of patients admitted with diverticulitis were treated with medical therapy. However, several recent studies have shown that outpatient treatment with antibiotics is safe and effective. The aim of this systematic review is to update the evidence published in the outpatient treatment of uncomplicated acute diverticulitis. We performed a systematic review according to the PRISMA guidelines and searched in MEDLINE and Cochrane databases all English-language articles on the management of acute diverticulitis using the following search terms: 'diverticulitis', 'outpatient', and 'uncomplicated'. Data were extracted independently by two investigators. A total of 11 articles for full review were yielded: one randomized controlled trial, eight prospective cohort studies, and two retrospective cohort studies. Treatment successful rate on an outpatient basis, which means that no further complications were reported, ranged from 91.5 to 100%. Fewer than 8% of patients were readmitted in the hospital. Intolerance to oral intake and lack of family or social support are common exclusion criteria used for this approach, whereas severe comorbidities are not definitive exclusion criteria in all the studies. Ambulatory treatment of uncomplicated acute diverticulitis is safe, effective, and economically efficient when applying an appropriate selection in most reviewed studies. PMID- 26891197 TI - Upregulating Hif-1alpha by Hydrogel Nanofibrous Scaffolds for Rapidly Recruiting Angiogenesis Relative Cells in Diabetic Wound. AB - Nonhealing chronic wounds on foot are one of the most dreaded complications of diabetes, and biomedical scaffolds remain an attractive option for repairing or regenerating tissues. Accelerating angiogenesis in the early stage after injury is critical to wound healing process; however, the scaffolds accelerate the angiogenesis in the beginning but with the acceleration of vessel network formation the scaffold network hinders the process. In this study, the water soluble drugs-loaded hydrogel nanofibrous scaffolds are designed for rapidly recruiting angiogenesis relative cells and promoting wound healing. The sustained release profile of desferrioxamine (DFO), which continues for about 72 h, leads to significantly increase of neovascularization. The majority of the scaffold is degraded in 14 d, leaving enough space for cell proliferation and vessel formation. The in vitro results show that the scaffolds upregulate the expression of Hif-1alpha and vascular endothelial growth factor, and enhance the interaction between fibroblasts and endothelial cells. The in vivo studies show a higher expression of angiogenesis related cytokines. This study demonstrates that the DFO released from hydrogel nanofibrous scaffolds of quick degradation can interfere with the required prolyl-hydroxylases cofactors by acting as Fe(2+) chelator and upregulate the expression of Hif-1alpha, leading to a significant increase of the neovascularization. PMID- 26891199 TI - (1) H and (13) C NMR spectral assignments of 30 novel n-methoxylated polyphenols containing thiourea skeletons. PMID- 26891200 TI - Narrow band imaging for the diagnosis of head and neck squamous cell carcinoma: A systematic review. AB - Narrow band imaging (NBI) is reported to improve the diagnostic accuracy of head and neck cancers. The purpose of this review was to evaluate the diagnostic accuracy of NBI in the literature. A systematic review was performed in PubMed, Web of Knowledge, and the Cochrane Library until March 2015. Two reviewers independently assessed articles and extracted data. Meta-analyses were performed in MetaDisc 1.6. Five hundred seventeen studies were identified and 17 were included in this study. Combined use of NBI and white light imaging (WLI) showed high diagnostic accuracies for primary, recurrent, and nasopharyngeal lesions. Methodological heterogeneity exists and meta-analyses were only appropriate for cancers of unknown primary (CUP) in which NBI performed on 115 patients across 4 studies demonstrated high sensitivity (74.1%; 95% confidence interval [CI] = 52.5% to 100%) and specificity (94.1%; 95% CI = 23.7% to 100%). NBI may further help identify lesions in CUP not seen by positron emission tomography (PET)-CT. NBI offers a high level of diagnostic accuracy for head and neck cancers. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2358-E2367, 2016. PMID- 26891201 TI - Doping-free bandgap tuning in one-dimensional Magneli-phase nanorods of Mo4O11. AB - We synthesized one-dimensional (1D) Magneli-phase nanorods of Mo4O11 using the hot filament metal-oxide vapor deposition technique. The 1D Magneli-phase Mo4O11 nanorods synthesized at 1000, 1050, 1100, 1150, and 1200 degrees C contain varying combinations of two orthorhombic (alpha) and monoclinic (eta) phases, and various mixtures of Mo(4+), Mo(5+) and Mo(6+) cations, while those synthesized at a higher temperature look bluer. The shifts of the transmittance maximum and absorbance minimum of the 1D Magneli-phase Mo4O11 nanorods are inversely and linearly proportional to the elevated temperature, verifying that the bandgaps (Eg) are inversely proportional to the elevated temperature. The bandgap (Eg) of the 1D Magneli-phase Mo4O11 nanorods can be tuned by simply controlling the synthesis temperature without doping with other materials, giving the 1D Magneli phase Mo4O11 nanorods good potential for use in optoelectronic nanodevices and bandgap engineering. PMID- 26891202 TI - Ilya Mark Scheinker: Controversial Neuroscientist and Refugee From National Socialist Europe. AB - Russian-born, Vienna-trained neurologist and neuropathologist Ilya Mark Scheinker collaborated with Josef Gerstmann and Ernst Straussler in 1936 to describe the familial prion disorder now known as Gerstmann-Straussler-Scheinker disease. Because of Nazi persecution following the annexation of Austria by Nazi Germany, Scheinker fled from Vienna to Paris, then after the German invasion of France, to New York. With the help of neurologist Tracy Putnam, Scheinker ended up at the University of Cincinnati, although his position was never guaranteed. He more than doubled his prior publications in America, and authored three landmark neuropathology textbooks. Despite his publications, he was denied tenure and had difficulty professionally in the Midwest because of prejudice against his European mannerisms. He moved back to New York for personal reasons in 1952, dying prematurely just 2 years later. Scheinker was twice uprooted, but persevered and eventually found some success as a refugee. PMID- 26891203 TI - Evidence-Based Update to the U.S. Centers for Disease Control and Prevention and Healthcare Infection Control Practices Advisory Committee Guideline for the Prevention of Surgical Site Infection: Developmental Process. AB - Recommendations in the "Guideline for Prevention of Surgical Site Infection, 1999" were based on experts' selective interpretation of the scientific evidence. Effective 2009, the U.S. Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee (HICPAC) updated their guideline development process. This is a narrative summary of the updated process focusing on key changes and challenges specific to the Guideline for Prevention of Surgical Site Infection. The guideline development process now incorporates evidence-based methodology and provides explicit links between the evidence and the recommendations using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. There is also participation by professional surgical societies, an updated guideline structure (core and procedure-specific sections), additional planned related manuscripts (introductions to the guideline and research opportunities), and new proposed venues for publication. The new CDC and HICPAC "Guideline for the Prevention of Surgical Site Infection" represents a substantial advancement from recommendations for infection control practices based on expert opinion to evidence-based practices. The new structure is meant to facilitate future updates, in particular, those addressing specialty or procedure-specific surgical site infection prevention questions. Increased presence by the surgical community through the professional surgical societies' engagement in the guideline development process, lead authorship of related manuscripts, and proposed publication in the surgical literature not only increase adherence by the surgical community, but also promote an ongoing collaboration with public health and other partners in a multidisciplinary approach to SSI prevention. PMID- 26891204 TI - Can Obviously Intoxicated Patrons Still Easily Buy Alcohol at On-Premise Establishments? AB - BACKGROUND: Excessive alcohol consumption at licensed alcohol establishments (i.e., bars and restaurants) has been directly linked to alcohol-related problems such as traffic crashes and violence. Historically, alcohol establishments have had a high likelihood of selling alcohol to obviously intoxicated patrons (also referred to as "overservice") despite laws prohibiting these sales. Given the risks associated with overservice and the need for up-to-date data, it is critical that we monitor the likelihood of sales to obviously intoxicated patrons. METHODS: To assess the current likelihood of a licensed alcohol establishment selling alcohol to an obviously intoxicated patron, we conducted pseudo-intoxicated purchase attempts (i.e., actors attempt to purchase alcohol while acting out obvious signs of intoxication) at 340 establishments in 1 Midwestern metropolitan area. We also measured characteristics of the establishments, the pseudo-intoxicated patrons, the servers, the managers, and the neighborhoods to assess whether these characteristics were associated with likelihood of sales of obviously intoxicated patrons. We assessed these associations with bivariate and multivariate regression models. RESULTS: Pseudo intoxicated buyers were able to purchase alcohol at 82% of the establishments. In the fully adjusted multivariate regression model, only 1 of the characteristics we assessed was significantly associated with likelihood of selling to intoxicated patrons-establishments owned by a corporate entity had 3.6 greater odds of selling alcohol to a pseudo-intoxicated buyer compared to independently owned establishments. CONCLUSIONS: Given the risks associated with overservice of alcohol, more resources should be devoted first to identify effective interventions for decreasing overservice of alcohol and then to educate practitioners who are working in their communities to address this public health problem. PMID- 26891209 TI - High spatial and temporal resolution cell manipulation techniques in microchannels. AB - The advent of microfluidics has enabled thorough control of cell manipulation experiments in so called lab on chips. Lab on chips foster the integration of actuation and detection systems, and require minute sample and reagent amounts. Typically employed microfluidic structures have similar dimensions as cells, enabling precise spatial and temporal control of individual cells and their local environments. Several strategies for high spatio-temporal control of cells in microfluidics have been reported in recent years, namely methods relying on careful design of the microfluidic structures (e.g. pinched flow), by integration of actuators (e.g. electrodes or magnets for dielectro-, acousto- and magneto phoresis), or integrations thereof. This review presents the recent developments of cell experiments in microfluidics divided into two parts: an introduction to spatial control of cells in microchannels followed by special emphasis in the high temporal control of cell-stimulus reaction and quenching. In the end, the present state of the art is discussed in line with future perspectives and challenges for translating these devices into routine applications. PMID- 26891210 TI - Time for reassessment of remote ischaemic preconditioning. PMID- 26891211 TI - Influence of complications following immediate breast reconstruction on breast cancer recurrence rates. AB - BACKGROUND: The rate of immediate breast reconstruction is rising. Postoperative infections are more frequent in patients who undergo reconstruction. The inflammatory response to a postoperative infection can increase the risk of tumour recurrence in other forms of cancer through the release of proinflammatory mediators. The aim of this study was to assess the relationship between complications and breast cancer recurrence in patients undergoing immediate reconstruction. METHODS: This was a review of a prospectively maintained database of all patients who had immediate breast reconstruction between 2004 and 2009 at Galway University Hospital, a tertiary breast cancer referral centre serving the west of Ireland. All patients had a minimum follow-up of 5 years. Outcomes assessed included the development of wound complications and breast cancer recurrence. The data were evaluated by univariable and multivariable Cox regression analysis. RESULTS: A total of 229 patients who underwent immediate reconstruction were identified. The overall 5-year recurrence-free survival rate was 85.6 per cent. Fifty-three patients (23.1 per cent) had wound complications, of whom 44 (19.2 per cent) developed a wound infection. There was a significantly greater risk of developing systemic recurrence among patients who experienced a postoperative wound complication compared with those without a complication (hazard ratio 4.94, 95 per cent c.i. 2.72 to 8.95; P < 0.001). This remained significant after adjusting for Nottingham Prognostic Index group in the multivariable analysis. The 5-year recurrence-free survival rate for patients who had a wound complication was 64 per cent, compared with 89.2 per cent in patients without a complication (P < 0.001). CONCLUSION: This study has demonstrated that wound complications after immediate breast reconstructive surgery have significant implications for patients with breast cancer. Strategies are required to minimize the risk of postoperative wound complications in patients with breast cancer undergoing immediate reconstruction. PMID- 26891205 TI - Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. AB - Statins are associated with delayed fibrosis progression and a reduced risk of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV). Limited data exist regarding the most effective type and dose of statin in this population. We sought to determine the impact of statin type and dose upon fibrosis progression and HCC in patients with HCV. Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified all subjects initiated on HCV antibody (anti-HCV) therapy from 2001 to 2014, and all incident cases of cirrhosis and HCC. Statin use was measured using cumulative defined daily dose (cDDD). Multivariable Cox's proportional hazard regression models were used to examine the relationship between statin use and development of cirrhosis and HCC. Among 9,135 eligible subjects, 1,649 developed cirrhosis and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.53, 0.68). The adjusted HRs (95% CI) of fibrosis progression with statin cDDD 28-89, 89-180, and >180 were 0.74 (0.59, 0.93), 0.71 (0.59, 0.88), and 0.6 (0.53, 0.68), respectively. Mean change in FIB-4 score with atorvastatin (n = 944) and fluvastatin (n = 34) was -0.17 and -0.13, respectively (P = 0.04), after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted HR: 0.51; 95% CI: 0.36, 0.72). A similar dose-response relationship was observed. CONCLUSION: In patients with chronic HCV, statin use was associated with a dose dependent reduction in incident cirrhosis and HCC. Atorvastatin and fluvastatin were associated with the most significant antifibrotic effects, compared with other statins. (Hepatology 2016;64:47-57). PMID- 26891214 TI - Making the elderly fit for surgery. PMID- 26891212 TI - Effect of ischaemic preconditioning on recurrence of hepatocellular carcinoma in an experimental model of liver steatosis. AB - BACKGROUND: Livers with parenchymal abnormalities tolerate ischaemia-reperfusion (IR) injury poorly. IR injury is a risk factor for hepatocellular carcinoma (HCC) recurrence. This study assessed the link between liver parenchymal abnormalities and HCC recurrence, and evaluated the protective effect of ischaemic preconditioning. METHODS: C57BL/6 mice were fed a choline-deficient diet for 6 and 12 weeks, or standard chow. Hepatic IR and ischaemic preconditioning were achieved by clamping liver blood inflow. Hepa 1-6 HCC cells were inoculated through the spleen. Thereafter, tumour burden, serum alpha-fetoprotein and cancer cell aggressiveness were compared among groups. RESULTS: Hepatocellular damage and expression of inflammatory genes (encoding interleukin 6, tumour necrosis factor alpha, hypoxia inducible factor 1alpha and E-selectin) were exacerbated after IR injury in mice with severe steatosis. Compared with control livers or those with minimal steatosis, livers exposed to a prolonged choline-deficient diet developed larger tumour nodules and had higher serum alpha-fetoprotein levels. Non-ischaemic liver lobes from mice with steatosis were not protected from accelerated tumour growth mediated by IR injury. This remote effect was linked to promotion of the aggressiveness of HCC cells. Ischaemic preconditioning before IR injury reduced the tumour burden to the level of that in non-ischaemic steatotic controls. This protective effect was associated with decreased cancer cell motility. CONCLUSION: Livers with steatosis tolerated IR poorly, contributing to more severe HCC recurrence patterns in mice with increasingly severe steatosis. IR injury also had a remote effect on cancer cell aggressiveness. Ischaemic preconditioning before IR injury reduced tumour load and serum alpha-fetoprotein levels. SURGICAL RELEVANCE: Liver ischaemia reperfusion (IR) injury is associated with organ dysfunction and surgical morbidity. Livers with steatosis tolerate IR injury poorly in the setting of both liver resection and liver transplantation. Ischaemic preconditioning is a simple method to mitigate IR injury. This study shows that ischaemic preconditioning of mouse livers with steatosis reduces ischaemia-mediated tumour growth acceleration. Liver parenchymal abnormalities such as warm IR injury and liver steatosis should be taken into account to predict accurately the risk of liver cancer recurrence after surgical management. Ischaemic preconditioning strategies may hold therapeutic potential not only to mitigate surgical morbidity but also to reduce postoperative recurrence of liver cancer. PMID- 26891206 TI - Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage. AB - Numerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on "outside-in" signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis. Stem Cells 2016;34:1455-1463. PMID- 26891216 TI - Black Raspberry Extract Increased Circulating Endothelial Progenitor Cells and Improved Arterial Stiffness in Patients with Metabolic Syndrome: A Randomized Controlled Trial. AB - Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% +/- 10% vs. 3% +/- 14%, P < .05). CD34/CD133(+) cells at 12-week follow-up were significantly higher in the black raspberry group compared to the placebo group (19 +/- 109/MUL vs. -28 +/- 57/MUL, P < .05). Decreases from the baseline in interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were significantly greater in the black raspberry group compared to the placebo group (-0.5 +/- 1.4 pg/mL vs. -0.1 +/- 1.1 pg/mL, P < .05 and -5.4 +/- 4.5 pg/mL vs. 0.8 +/- 4.0 pg/mL, P < .05, respectively). Increases from the baseline in adiponectin levels (2.9 +/- 2.1 MUg/mL vs. -0.2 +/- 2.5 MUg/mL, P < .05) were significant in the black raspberry group. The use of black raspberry significantly lowered the augmentation index and increased circulating EPCs, thereby improving CV risks in patients with metabolic syndrome during the 12-week follow-up. PMID- 26891217 TI - Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014. AB - BACKGROUND: The aim of this study was to evaluate the treatment reality for outpatients with immune thrombocytopenia (ITP) managed by hematologists in routine care. PATIENTS AND METHODS: All patients with ITP diagnosed between 06/1995 and 12/2014 in a community-based oncology group practice in Germany were retrospectively analyzed. RESULTS: 422 patients with a median age of 55 years (range 7-91 years) were evaluated. 57% were female and 43% male. Only 198 (47%) patients needed therapy. First-line therapy (n = 198) consisted of steroids in 81%, intravenous immunoglobulins (IVIG) in 12%, and IVIG plus steroids in 6%. Patients received a median of 2 (range 1-10) lines of therapy. The most frequently used treatment modalities were steroids in 93%, IVIG in 55%, splenectomy in 21%, and other immunosuppressive agents (OISA) in 23% of patients. Rituximab and thrombopoietin receptor agonists (TRAs) were used in 10% and 6% only. 9 (2%) patients needed hospitalization due to bleeding complications. 72% of patients achieved a durable remission after their last line of therapy. 1 (0.2%) patient died due to bleeding complications. CONCLUSION: The treatment modalities most frequently used are steroids, immunoglobulins, splenectomy, and OISA. Rituximab and TRAs are only used infrequently. 72% of ITP patients achieve durable remissions. The rate of hospital admissions due to bleeding complications and the ITP-related mortality are low. The majority of ITP patients can be safely managed by hematologists on an outpatient basis. PMID- 26891219 TI - The effects of noise in cardiac diffusion tensor imaging and the benefits of averaging complex data. AB - There is growing interest in cardiac diffusion tensor imaging (cDTI), but, unlike other diffusion MRI applications, there has been little investigation of the effects of noise on the parameters typically derived. One method of mitigating noise floor effects when there are multiple image averages, as in cDTI, is to average the complex rather than the magnitude data, but the phase contains contributions from bulk motion, which must be removed first. The effects of noise on the mean diffusivity (MD), fractional anisotropy (FA), helical angle (HA) and absolute secondary eigenvector angle (E2A) were simulated with various diffusion weightings (b values). The effect of averaging complex versus magnitude images was investigated. In vivo cDTI was performed in 10 healthy subjects with b = 500, 1000, 1500 and 2000 s/mm(2). A technique for removing the motion-induced component of the image phase present in vivo was implemented by subtracting a low resolution copy of the phase from the original images before averaging the complex images. MD, FA, E2A and the transmural gradient in HA were compared for un-averaged, magnitude- and complex-averaged reconstructions. Simulations demonstrated an over-estimation of FA and MD at low b values and an under estimation at high b values. The transition is relatively signal-to-noise ratio (SNR) independent and occurs at a higher b value for FA (b = 1000-1250 s/mm(2)) than MD (b ~ 250 s/mm(2)). E2A is under-estimated at low and high b values with a transition at b ~ 1000 s/mm(2), whereas the bias in HA is comparatively small. The under-estimation of FA and MD at high b values is caused by noise floor effects, which can be mitigated by averaging the complex data. Understanding the parameters of interest and the effects of noise informs the selection of the optimal b values. When complex data are available, they should be used to maximise the benefit from the acquisition of multiple averages. The combination of complex data is also a valuable step towards segmented acquisitions. PMID- 26891218 TI - Evaluation of a Rapid Point of Care Test for Detecting Acute and Established HIV Infection, and Examining the Role of Study Quality on Diagnostic Accuracy: A Bayesian Meta-Analysis. AB - INTRODUCTION: Fourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy. METHODS: Two independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional). RESULTS: The overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3-99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1-93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8-100] and 99.6%, 95% CrI [99.0-99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7-99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1-44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality. CONCLUSIONS: Although the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation. PMID- 26891220 TI - Purification and Characterization of Glutaminase Free Asparaginase from Enterobacter cloacae: In-Vitro Evaluation of Cytotoxic Potential against Human Myeloid Leukemia HL-60 Cells. AB - Asparaginase is an important antileukemic agent extensively used worldwide but the intrinsic glutaminase activity of this enzymatic drug is responsible for serious life threatening side effects. Hence, glutaminase free asparaginase is much needed for upgradation of therapeutic index of asparaginase therapy. In the present study, glutaminase free asparaginase produced from Enterobacter cloacae was purified to apparent homogeneity. The purified enzyme was found to be homodimer of approximately 106 kDa with monomeric size of approximately 52 kDa and pI 4.5. Purified enzyme showed optimum activity between pH 7-8 and temperature 35-40 degrees C, which is close to the internal environment of human body. Monovalent cations such as Na+ and K+ enhanced asparaginase activity whereas divalent and trivalent cations, Ca2+, Mg2+, Zn2+, Mn2+, and Fe3+ inhibited the enzyme activity. Kinetic parameters Km, Vmax and Kcat of purified enzyme were found to be 1.58*10-3 M, 2.22 IU MUg-1 and 5.3 * 104 S-1, respectively. Purified enzyme showed prolonged in vitro serum (T1/2 = ~ 39 h) and trypsin (T1/2 = ~ 32 min) half life, which is therapeutically remarkable feature. The cytotoxic activity of enzyme was examined against a panel of human cancer cell lines, HL-60, MOLT-4, MDA-MB-231 and T47D, and highest cytotoxicity observed against HL-60 cells (IC50 ~ 3.1 IU ml-1), which was comparable to commercial asparaginase. Cell and nuclear morphological studies of HL-60 cells showed that on treatment with purified asparaginase symptoms of apoptosis were increased in dose dependent manner. Cell cycle progression analysis indicates that enzyme induces apoptosis by cell cycle arrest in G0/G1 phase. Mitochondrial membrane potential loss showed that enzyme also triggers the mitochondrial pathway of apoptosis. Furthermore, the enzyme was found to be nontoxic for human noncancerous cells FR-2 and nonhemolytic for human erythrocytes. PMID- 26891222 TI - Microfluidic Device for the Measurement of Amino Acid Secretion Dynamics from Murine and Human Islets of Langerhans. AB - Islets of Langerhans are the regulators of in vivo blood glucose levels through the secretion of endocrine hormones. Amino acids, released from various cells within islets or from intrapancreatic neurons, are hypothesized to further adjust hormone secretions. In contrast to the well-accepted mechanism of glucose stimulated insulin secretion, several questions remain as to the function of amino acids in the regulation of hormone release from islets. To understand the autocrine and paracrine roles that amino acids play in islet physiology, a microfluidic system was developed to perform online monitoring of the secretion profiles of amino acids from 2-5 islets. The device contained an islet chamber with the ability to perfuse stimulants and an amino acid measurement system with derivatization and electrophoretic separation integrated on a single microchip. The setup was optimized to allow -15 kV to be applied to the device for high efficiency and rapid separations of derivatized amino acids. The compositions of the derivatization and separation buffers were optimized to prevent precipitations in the channels, which allowed continuous monitoring of secretion for over 2 h. With this method, 10 amino acids were resolved with limits of detection ranging from 1 to 20 nM. When murine islets were perfused with 3 mM glucose, the secretion rates of 9 amino acids were measured and ranged from 30 to 400 fmol islet(-1) min(-1). As the glucose concentration was increased to 20 mM, the dynamic changes of amino acids were monitored. The biological relevance of the amino acid secretions was verified using 2,4-dinitrophenol as an inhibitor of the proton motive force. The microfluidic system was also used to measure dynamic changes of amino acid release from human islets, which showed different release profiles compared to their murine counterparts. PMID- 26891223 TI - Variations of mucosal-sparing septectomy for endonasal approach to the craniocervical junction. AB - OBJECTIVES/HYPOTHESIS: Recent advances in surgical techniques have rendered the craniocervical junction (CCJ) accessible transnasally. Endoscopic endonasal transclival and transodontoid approaches are routinely performed in leading skull base centers. Usually, these approaches involve a posterior bony and mucosal septectomy, which may compromise the vascularized pedicled nasoseptal flap (PNSF), a robust reconstructive option for repair of large skull base defects. With the possibility of an intraoperative cerebrospinal fluid leak and the reported success of the PNSF for repair of these defects, preserving the integrity of the PNSF is beneficial during the endoscopic endonasal approach to the CCJ. We describe three new variations/refinements of the endoscopic endonasal approach to the CCJ that preserve the mucosal integrity of the posterior nasal septum and PNSF. METHODS: Photo and video documentation of cadaveric dissections. RESULTS: The steps required for the different variations in approaching the CCJ are demonstrated. These three options are: 1) nonopposing Killian incisions with submucosal elevation of PNSFs laterally under the inferior turbinates (the PNSFs are retracted laterally and left attached superiorly onto the nasal septum and laterally under the inferior turbinate); 2) bilateral non-opposing PNSFs tucked beneath their respective middle turbinate or into the sphenoid sinus; and 3) a hybrid approach combining option 1 performed on one side and option 2 on the contralateral side. All three options allowed for a mucosal-sparing septectomy to provide ample access to the CCJ. CONCLUSION: These variations/refinements of the mucosal-sparing approach to the CCJ allowed adequate surgical access with sufficient maneuverability while preserving both PNSFs. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:2220-2225, 2016. PMID- 26891224 TI - Morphological dependence of silver electrodeposits investigated by changing the ionic liquid solvent and the deposition parameters. AB - The low toxicity and environmentally compatible ionic liquids (ILs) are alternatives to the toxic and harmful cyanide-based baths used in industrial silver electrodeposition. Here, we report the successful galvanostatic electrodeposition of silver films using the air and water stable ILs 1-ethyl-3 methylimidazolium trifluoromethylsulfonate ([EMIM]TfO) and 1-H-3 methylimidazolium hydrogen sulphate ([HMIM(+)][HSO4(-)]) as solvents and AgTfO as the source of silver. The electrochemical deposition parameters were thoughtfully studied by cyclic voltammetry before deposition. The electrodeposits were characterized by scanning electron microscopy coupled with X-ray energy dispersive spectroscopy and X-ray diffraction. Molecular dynamics (MD) simulations were used to investigate the structural dynamic and energetic properties of AgTfO in both ILs. Cyclic voltammetry experiments revealed that the reduction of silver is a diffusion-controlled process. The morphology of the silver coatings obtained in [EMIM]TfO is independent of the applied current density, resulting in nodular electrodeposits grouped as crystalline clusters. However, the current density significantly influences the morphology of silver electrodeposits obtained in [HMIM(+)][HSO4(-)], thus evolving from dendrites at 15 mA cm(-2) to the coexistence of dendrites and columnar shapes at 30 mA cm(-2). These differences are probably due to the greater interaction of Ag(+) with [HSO4(-)] than with TfO(-), as indicated by the MD simulations. The morphology of Ag deposits is independent of the electrodeposition temperature for both ILs, but higher values of temperature promoted increased cluster sizes. Pure face-centred cubic polycrystalline Ag was deposited on the films with crystallite sizes on the nanometre scale. The morphological dependence of Ag electrodeposits obtained in the [HMIM(+)][HSO4(-)] IL on the current density applied opens up the opportunity to produce different and predetermined Ag deposits. PMID- 26891221 TI - Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication. AB - Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication. PMID- 26891226 TI - Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes. AB - BACKGROUND: Pancreatic organ-specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D. METHODS: Ten Italian children with beta cell autoimmunity at risk for T1D and 10 healthy children were involved in a case control study. The lactulose/mannitol test was used to assess intestinal permeability. Analysis of microbiota composition was performed using polymerase chain reaction followed by denaturing gradient gel electrophoresis, based on the 16S rRNA gene. RESULTS: Intestinal permeability was significantly higher in children at risk for T1D than in healthy controls. Moreover, the gut microbiota of the former differed from that of the latter group: Three microorganisms were detected - Dialister invisus, Gemella sanguinis and Bifidobacterium longum - in association with the pre-pathologic state. CONCLUSIONS: The results of this study validated the hypothesis that increased intestinal permeability together with differences in microbiota composition are contemporaneously associated with the pre-pathological condition of T1D in a sample of Italian children. Further studies are necessary to confirm the microbial markers identified in this sample of children as well as to clarify the involvement of microbiota modifications in the mechanisms leading to increased permeability and the autoimmune mechanisms that promote diabetes onset. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891227 TI - Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review. AB - BACKGROUND: There is a proven link between Down syndrome and the early development of the neuropathological features of Alzheimer's disease (AD). Changes in the personality and behavior of adults with Down syndrome might indicate the early stages of dementia or of frontotemporal lobar degeneration. The objective of this study was to investigate the executive functions and changes in behavior associated with frontal lobe degeneration in individuals with Down syndrome who develop AD. We conducted a systematic review selecting studies employing cognitive assessments. SUMMARY: We identified few studies using objective measurements to determine whether cognitive aspects associated with the frontal lobe correlate with dementia in this population. We observed a tendency toward such correlations. KEY MESSAGES: There is a need for further studies in which objective measures of cognitive and behavioral factors are evaluated together with data related to brain function and morphology. PMID- 26891225 TI - RAB-6.1 and RAB-6.2 Promote Retrograde Transport in C. elegans. AB - Retrograde transport is a critical mechanism for recycling certain membrane cargo. Following endocytosis from the plasma membrane, retrograde cargo is moved from early endosomes to Golgi followed by transport (recycling) back to the plasma membrane. The complete molecular and cellular mechanisms of retrograde transport remain unclear. The small GTPase RAB-6.2 mediates the retrograde recycling of the AMPA-type glutamate receptor (AMPAR) subunit GLR-1 in C. elegans neurons. Here we show that RAB-6.2 and a close paralog, RAB-6.1, together regulate retrograde transport in both neurons and non-neuronal tissue. Mutants for rab-6.1 or rab-6.2 fail to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. Loss of both rab-6.1 and rab-6.2 results in an additive effect on GLR-1 retrograde recycling, indicating that these two C. elegans Rab6 isoforms have overlapping functions. MIG-14 (Wntless) protein, which undergoes retrograde recycling, undergoes a similar degradation in intestinal epithelia in both rab-6.1 and rab 6.2 mutants, suggesting a broader role for these proteins in retrograde transport. Surprisingly, MIG-14 is localized to separate, spatially segregated endosomal compartments in rab-6.1 mutants compared to rab-6.2 mutants. Our results indicate that RAB-6.1 and RAB-6.2 have partially redundant functions in overall retrograde transport, but also have their own unique cellular- and subcellular functions. PMID- 26891229 TI - Water-Soluble NIR-Absorbing Rylene Chromophores for Selective Staining of Cellular Organelles. AB - Biocompatible organic dyes emitting in the near-infrared are highly desirable in fluorescence imaging techniques. Herein we report a synthetic approach for building novel small peri-guanidine-fused naphthalene monoimide and perylene monoimide chromophores. The presented structures possess near-infrared absorption and emission, high photostability, and good water solubility. After a fast cellular uptake, they selectively stain mitochondria with a low background in live and fixed cells. They can be additionally modified in a one-step reaction with functional groups for covalent labeling of proteins. The low cytotoxicity allows a long time exposure of live cells to the dyes without the necessity of washing. Successful application in localization super-resolution microscopy was demonstrated in phosphate-buffered saline without any reducing or oxidizing additives. PMID- 26891228 TI - Synergistic Control of Kinetochore Protein Levels by Psh1 and Ubr2. AB - The accurate segregation of chromosomes during cell division is achieved by attachment of chromosomes to the mitotic spindle via the kinetochore, a large multi-protein complex that assembles on centromeres. The budding yeast kinetochore comprises more than 60 different proteins. Although the structure and function of many of these proteins has been investigated, we have little understanding of the steady state regulation of kinetochores. The primary model of kinetochore homeostasis suggests that kinetochores assemble hierarchically from the centromeric DNA via the inclusion of a centromere-specific histone into chromatin. We tested this model by trying to perturb kinetochore protein levels by overexpressing an outer kinetochore gene, MTW1. This increase in protein failed to change protein recruitment, consistent with the hierarchical assembly model. However, we find that deletion of Psh1, a key ubiquitin ligase that is known to restrict inner kinetochore protein loading, does not increase levels of outer kinetochore proteins, thus breaking the normal kinetochore stoichiometry. This perturbation leads to chromosome segregation defects, which can be partially suppressed by mutation of Ubr2, a second ubiquitin ligase that normally restricts protein levels at the outer kinetochore. Together these data show that Psh1 and Ubr2 synergistically control the amount of proteins at the kinetochore. PMID- 26891230 TI - Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections. AB - We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013-2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (<5 single-nucleotide polymorphisms), and >21,000 single nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures. PMID- 26891232 TI - Human CYP27A1 catalyzes hydroxylation of beta-sitosterol and ergosterol. AB - beta-Sitosterol and ergosterol are the equivalents of cholesterol in plants and fungi, respectively, and common sterols in the human diet. In the current work, both were identified as novel CYP27A1 substrates by in vitro experiments applying purified human CYP27A1 and its redox partners adrenodoxin (Adx) and adrenodoxin reductase (AdR). A Bacillus megaterium based biocatalyst recombinantly expressing the same proteins was utilized for the conversion of the substrates to obtain sufficient amounts of the novel products for a structural NMR analysis. beta Sitosterol was found to be converted into 26-hydroxy-beta-sitosterol and 29 hydroxy-beta-sitosterol, whereas ergosterol was converted into 24 hydroxyergosterol, 26-hydroxyergosterol and 28-hydroxyergosterol. PMID- 26891231 TI - MiR-449a Affects Epithelial Proliferation during the Pseudoglandular and Canalicular Phases of Avian and Mammal Lung Development. AB - Congenital diaphragmatic hernia is associated with pulmonary hypoplasia and respiratory distress, which result in high mortality and morbidity. Although several transgenic mouse models of lung hypoplasia exist, the role of miRNAs in this phenotype is incompletely characterized. In this study, we assessed microRNA expression levels during the pseudoglandular to canalicular phase transition of normal human fetal lung development. At this critical time, when the distal respiratory portion of the airways begins to form, microarray analysis showed that the most significantly differentially expressed miRNA was miR-449a. Prediction algorithms determined that N-myc is a target of miR-449a and identified the likely miR-449a:N-myc binding sites, confirmed by luciferase assays and targeted mutagenesis. Functional ex vivo knock-down in organ cultures of murine embryonic lungs, as well as in ovo overexpression in avian embryonic lungs, suggested a role for miR-449a in distal epithelial proliferation. Finally, miR-449a expression was found to be abnormal in rare pulmonary specimens of human fetuses with Congenital Diaphragmatic Hernia in the pseudoglandular or canalicular phase. This study confirms the conserved role of miR-449a for proper pulmonary organogenesis, supporting the delicate balance between expansion of progenitor cells and their terminal differentiation, and proposes the potential involvement of this miRNA in human pulmonary hypoplasia. PMID- 26891233 TI - Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component. AB - Carcinosarcomas (CS) are biphasic tumors with malignant epithelial and mesenchymal elements. The sarcomatoid elements of CS can include chondrosarcoma, malignant fibrous histiocytoma, osteosarcoma, leiomyosarcoma, fibrosarcoma, or liposarcoma. CS of the upper urinary tract are extremely rare but are associated with a poor prognosis. We report a case of a 44-year-old man with a localized right renal pelvis mass treated with a right nephroureterectomy. The pathological examination showed a high-grade urothelial carcinoma of the renal pelvis, stage III (pT3aNxM0). A few days later, he developed lower back pain, hematuria, cough with hemoptoic sputum and progressive dyspnea. Radiological explorations showed multiple bilateral lung nodules and a retroperitoneal mass. A CT-guided biopsy of the retroperitoneal mass revealed a high-grade angiosarcoma. A review of the nephrectomy specimen showed a microscopic focus of angiosarcoma in the urothelial carcinoma. Therefore, the initial diagnosis was changed to CS of the renal pelvis with an angiosarcoma component. The patient developed progressive respiratory failure and died 8 weeks after surgery. An autopsy revealed a large retroperitoneal mass with metastatic nodules to the abdominal wall, diaphragm, small intestine, liver, spleen, and lung. All lesions were angiosarcoma, with no evidence of urothelial carcinoma. This is the first case reported of a patient with CS of the upper urinary tract with an angiosarcoma component with a very aggressive course that caused the immediate appearance of multiple angiosarcoma metastases. We also describe the clinical and molecular characteristics of CS, which will help to contribute to a better understanding of this type of tumor. PMID- 26891234 TI - Photochemical Oxidative Growth of Iridium Oxide Nanoparticles on CdSe@CdS Nanorods. AB - We demonstrate a procedure for the photochemical oxidative growth of iridium oxide catalysts on the surface of seeded cadmium selenide-cadmium sulfide (CdSe@CdS) nanorod photocatalysts. Seeded rods are grown using a colloidal hot injection method and then moved to an aqueous medium by ligand exchange. CdSe@CdS nanorods, an iridium precursor and other salts are mixed and illuminated. The deposition process is initiated by absorption of photons by the semiconductor particle, which results with formation of charge carriers that are used to promote redox reactions. To insure photochemical oxidative growth we used an electron scavenger. The photogenerated holes oxidize the iridium precursor, apparently in a mediated oxidative pathway. This results in the growth of high quality crystalline iridium oxide particles, ranging from 0.5 nm to about 3 nm, along the surface of the rod. Iridium oxide grown on CdSe@CdS heterostructures was studied by a variety of characterization methods, in order to evaluate its characteristics and quality. We explored means for control over particle size, crystallinity, deposition location on the CdS rod, and composition. Illumination time and excitation wavelength were found to be key parameters for such control. The influence of different growth conditions and the characterization of these heterostructures are described alongside a detailed description of their synthesis. Of significance is the fact that the addition of iridium oxide afforded the rods astounding photochemical stability under prolonged illumination in pure water (alleviating the requirement for hole scavengers). PMID- 26891236 TI - Bioisosteric Exchange of Csp3 -Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues. AB - Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpenin A5, are described. These analogues were selected on the basis of Cl->CH3 or H3 C->Cl exchanges in the side-chain of atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC50 values. This suggests that Cl<->Me bioisosteric exchange can be realized in aliphatic settings. PMID- 26891235 TI - Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta Analysis of Randomized Controlled Trials. AB - BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects. METHODS: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia). RESULTS: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67 0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased. CONCLUSION: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI. PMID- 26891237 TI - Modulation of host CD59 expression by varicella-zoster virus in human xenografts in vivo. AB - Varicella-zoster virus (VZV) is the causative agent of both chickenpox (varicella) and shingles (zoster). VZV survives host defenses, even with an intact immune system, and disseminates in the host before causing disease. To date, several diverse immunomodulatory strategies used by VZV to undermine host immunity have been identified; however, few studies have addressed the complement evasion strategies used by this virus. Here, we show that expression of CD59, which is a key member of host regulators of complement activation (RCA), is significantly upregulated in response to VZV infection in human T cells and dorsal root ganglia (DRG) but not in human skin xenografts in SCID-hu mice in vivo. This is the first report demonstrating that VZV infection upregulates host CD59 expression in a tissue-specific manner in vivo, which may aid VZV in complement evasion and pathogenesis. PMID- 26891238 TI - A systematic review of the diagnostic test accuracy of brief cognitive tests to detect amnestic mild cognitive impairment. AB - OBJECTIVE: People with amnestic mild cognitive impairment (aMCI) are at an increased risk of developing dementia. Efficient ways of identifying this 'at risk' population are required for larger-scale research studies. This systematic review describes the diagnostic accuracy of brief cognitive tests for detecting aMCI. METHODS: Fifteen databases were searched from 1999 to July 2013 to identify papers for inclusion. Prospective studies assessing the diagnostic test accuracy of simple and brief cognitive tests for identifying people with aMCI against a reference standard (Petersen criteria) were included. Sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Predictive validity and test-retest reliability were also extracted, when provided. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. RESULTS: Thirty-nine studies assessing 42 index tests were included. The Montreal Cognitive Assessment was the most comprehensively assessed test with evidence of high sensitivity for aMCI and good test-retest reliability, but low specificity was reported by the only study judged to be at low risk of bias. Other brief cognitive tests that include an assessment of word recall and multi-task tests that assess several cognitive domains were also found to exhibit high sensitivities and reasonable specificities. However, the confidence of the findings was affected by overall low quality of the contributing studies. CONCLUSION: Several brief cognitive tests have shown promising diagnostic test accuracy results for identifying aMCI. However, concerns over the quality of the constituent studies and lack of evidence on the predictive validity of these tests mean that new validation studies are warranted. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891239 TI - Inkjet-Assisted Nanotransfer Printing for Large-Scale Integrated Nanopatterns of Various Single-Crystal Organic Materials. AB - Inkjet-assisted nanotransfer printing (inkjet-NTP) facilitates spatial control of many arrays of various organic functional materials on a single substrate with a high-throughput integration process, enabling monolithic integration of various organic nanopatterns. Inkjet-NTP enables wafer-scale organic electronic circuits composed of field-effect transistors, complementary inverters, and p-n diodes, demonstrating its capability to produce a high-performance, multifunctional organic chip. PMID- 26891240 TI - Olfactory bulbectomy-induced changes in phospholipids and protein profiles in the hippocampus and prefrontal cortex of rats. A preliminary study using a FTIR spectroscopy. AB - BACKGROUND: Dysfunctions in neuronal proteins can lead to development of depression. Lipids determine the localization and function of proteins in the cell membrane and thereby regulate synaptic throughput in neurons. The aim of study was to examine changes in the phospholipid-protein balance in the olfactory bulbectomy (OB) model of depression in rats using a Fourier transform infra-red (FTIR) spectroscopy. METHODS: Sprague Dawley rats were subjected to the OB procedure and treated with amitriptyline (AMI, 10mg/kg). The FTIR measurements were performed in the hippocampus and prefrontal cortex. RESULTS: The obtained results show a decrease in the phospholipids and protein fractions (as well as changes in their secondary structures) in both brain areas of bulbectomized rats. AMI treatment reduced phospholipids' and increased the proteins' brain level, yet did not affect the level of phospholipids or increase the proteins in OB rats. Second derivatives calculated from the FTIR spectra provided information that the proteins (but not phospholipids) in both structures of the OB_AMI rats were normalized after antidepressant treatment. CONCLUSIONS: Our findings prove that the changes in the phospholipid-protein balance in the hippocampus and prefrontal cortex may be related to depressive disorders, thus leading to the development of adverse changes in the molecules necessary for the correct functioning of the brain. Furthermore, these results suggest a stability of the structure changes/damage of phospholipids in depression, which are present in brain tissues even after effective pharmacotherapy. This study also shows that an infrared spectroscopy can be applied for monitoring changes in mood disorders. PMID- 26891241 TI - The effects of silibin administration for different time periods on mouse liver with Ehrlich ascites carcinoma. AB - BACKGROUND: Ehrlich ascites carcinoma is the one of the animal cancer models having high malignancy and rapid growth resistance. Silibin has reported to be an antioxidant in previous studies. We aimed to investigate the effects of silibin on mouse liver with Ehrlich ascites tumor (EAT) cells in different time periods. METHODS: Balb/c mice were divided into five groups. Group I (Control): The saline buffer (sb) was injected intraperitoneally (ip) to the mice for 15 days. Group II (Silibin): 150mg/kg silibin was injected ip for 15 days. Group III (Ehrlich): 2*10(5) cells were transferred from the donor mouse to healthy mice on first day. Group IV (Ehrlich+Silibin): Silibin was given between 5th and 15th days to mice inoculated with EAT. Group V (Silibin+Ehrlich): Silibin was injected for 15 days after EAT cells. The liver sections were stained with matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), caspase 3, caspase 8, and proliferating cell nuclear antigen (PCNA) antibodies by the streptavidin-biotin-peroxidase technique. Biochemical analysis and Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick-end labeling (TUNEL) method were performed in the liver. RESULTS: Superoxide dismutase levels of liver increased in Ehrlich+Silibin group compared with Ehrlich group. Malondialdehyde levels significantly decreased in Silibin+Ehrlich group compared with Ehrlich+Silibin. MMP-2 and MMP-9 immunopositive cells increased in Silibin+Ehrlich compared with Ehrlich group. Caspase 3 and TUNEL signals significantly increased in Silibin+Ehrlich group compared with Ehrlich group. PCNA positive signals significantly increased in Ehrlich+Silibin group compared with Ehrlich group. CONCLUSION: According to our findings, we suggest that silibin treatment after EAT cells inoculation has more effective than concurrently EAT and silibin treatment. PMID- 26891243 TI - Management of side effects of mTOR inhibitors in tuberous sclerosis patients. AB - mTOR inhibitors represent a relatively new therapeutic option in the management of patients affected by tuberous sclerosis complex (TSC). Randomized clinical trials support the use of everolimus in the treatment of subependymal giant cell astrocytomas (SEGA) and renal angiomyolipomas (AML) related to TSC. Accumulating data suggest also systemic disease-modifying potential of mTOR inhibitors. Given that increasing number of patients with TSC receive mTOR inhibitors, the issue of adverse events associated with this therapy becomes practically important. In the present study we provide the overview of clinical manifestations and therapeutic options for the most common adverse events related to mTOR inhibitors in TSC patients. PMID- 26891244 TI - Role of silicon dangling bonds in the electronic properties of epitaxial graphene on silicon carbide. AB - In this paper, we study the electronic properties of epitaxial graphene (EG) on silicon carbide by means of ab initio calculations based on the local spin density approximation + U method taking into account the Coulomb interaction between Si localized electrons. We show that this interaction is not completely suppressed but is screened by carbon layers grown on-top of silicon carbide. This finding leads to a good qualitative understanding of the experimental results reported on EG on silicon carbide. Our results highlight the presence of the Si localized states and might explain the anomalous Hanle curve and the high values of spin relaxation time in EG. PMID- 26891242 TI - Antinociceptive activity of novel amide derivatives of imidazolidine-2,4-dione in a mouse model of acute pain. AB - BACKGROUND: Antiepileptic drugs are commonly used in non-epileptic disorders. For example, phenytoin and levetiracetam demonstrate analgesic properties in rodent models of pain. In order to enhance their antinociceptive activity, structural features of phenytoin and levetiracetam, such as imidazolidine-2,4-dione and amide bond in alkyl chain, were combined in one molecule. Furthermore, in preliminary studies, methoxyphenylpiperazinpropyl derivatives of imidazolidine 2,4-dione acted as antinociceptive agents in several rodent models of acute pain. METHODS: The final compounds and the reference drugs - levetiracetam and phenytoin were evaluated in the hot plate test to assess their antinociceptive activity in this acute pain model. Furthermore, for the analgesic active compounds the impact on animals' locomotor activity and motor performance were estimated and the affinity to serotonergic (5-HT1A, 5-HT7) and adrenergic (alpha1) receptors was determined. RESULTS: Three of the tested compounds: 7, 15 and 18 showed statistically significant antinociceptive properties at the dose of 30mg/kg. Among them, compound 18, 1-methyl-3-[1-(morpholin-4-yl)-1-oxobutan-2 yl]imidazolidine-2,4-dione, exhibited the most significant and long-lasting antinociceptive activity. Noteworthy, this activity was not associated with a negative effect on animals' motor functions. Serotonergic or adrenergic neurotransmission is not involved in this antinociceptive effect. CONCLUSION: Some amide derivatives of imidazolidine-2,4-diones possess antinociceptive properties in mice but further studies are needed to explain their mechanism of action and assess their toxicity. PMID- 26891246 TI - pH-Responsive Hydrogel With an Anti-Glycation Agent for Modulating Experimental Periodontitis. AB - BACKGROUND: Stimulus-responsive devices have emerged as a novel approach for local drug delivery. This study investigates the feasibility of a novel chitosan based, pH-responsive hydrogel loaded with N-phenacylthiazolium bromide (PTB), which cleaves the crosslinks of advanced glycation end products on the extracellular matrix. METHODS: A chitosan-based hydrogel loaded with PTB was fabricated, and the in vitro release profile was evaluated within pH 5.5 to 7.4. BALB/cJ mice and Sprague-Dawley rats were used to evaluate the effects during the induction and recovery phases of periodontitis, respectively, and animals in each phase were divided into four groups: 1) no periodontitis induction; 2) ligature induced experimental periodontitis (group PR); 3) experimental periodontitis plus hydrogel without PTB (group PH); and 4) experimental periodontitis plus hydrogel with PTB (group PP). The therapeutic effects were evaluated by microcomputed tomographic imaging of periodontal bone level (PBL) loss and histomorphometry for inflammatory cell infiltration and collagen density. RESULTS: PTB was released faster at pH 5.5 to 6.5 and consistently slower at pH 7.4. In the induction phase, PBL and inflammatory cell infiltration were significantly reduced in group PP relative to group PR, and the loss of collagen matrix was significantly reduced relative to that observed in group PH. In the recovery phase, PBL and inflammatory cell infiltration were significantly reduced, and significantly greater collagen deposition was noted in group PP relative to groups PR and PH at 4 and 14 days after silk removal. CONCLUSION: Chitosan-based, pH-responsive hydrogels loaded with PTB can retard the initiation of and facilitate the recovery from experimental periodontitis. PMID- 26891245 TI - Is "Sexual Competence" at First Heterosexual Intercourse Associated With Subsequent Sexual Health Status? AB - The timing of first sexual intercourse is often defined in terms of chronological age, with particular focus on "early" first sex. Arguments can be made for a more nuanced concept of readiness and appropriateness of timing of first intercourse. Using data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), conducted in 2010-2012, this study examined whether a context-based measure of first intercourse-termed sexual competence-was associated with subsequent sexual health in a population-based sample of 17-to 24-year-olds residing in Britain (n = 2,784). Participants were classified as "sexually competent" at first intercourse if they reported the following four criteria: contraceptive protection, autonomy of decision (not due to external influences), that both partners were "equally willing," and that it happened at the "right time." A lack of sexual competence at first intercourse was independently associated with testing positive for human papillomavirus (HPV) at interview; low sexual function in the past year; and among women only, reported sexually transmitted infection (STI) diagnosis ever; unplanned pregnancy in the past year; and having ever experienced nonvolitional sex. These findings provide empirical support for defining the nature of first intercourse with reference to contextual aspects of the experience, as opposed to a sole focus on chronological age at occurrence. PMID- 26891247 TI - Depression and health-related quality of life among persons with sensory disabilities in a health professional shortage area. AB - OBJECTIVE: The authors examined depression and health-related quality of life among individuals with self-reported sensory impairments living in a health professional shortage area. RESEARCH METHOD: Health surveys of residents were conducted in 2006 and 2010. Responses were analyzed by groups of residents reporting vision loss, hearing loss, dual hearing and vision loss, and no sensory loss. In 2006, the total sample size was n = 2,591, and in 2010, it was n = 3,955. MAIN OUTCOME MEASURES: The CESD-5 scale (Shrout & Yager, 1989) was included in 2006, and the PHQ-9 (Kroenke, Spitzer, & Williams, 2001) was included in 2010. Rates of depression on the CESD-5 were determined by the recommended cut off scores and on the PHQ-9 by the recommended algorithm. The Centers for Disease Control (CDC) Healthy Days instrument (Moriarty, Zack, & Kobau, 2003) was used in both surveys to assess health-related quality of life. RESULTS: In both surveys, individuals who reported sensory loss had higher rates of depression and lower health-related quality of life than individuals with no reported sensory loss. CONCLUSIONS: Individuals reporting sensory loss had high rates of depression and a compromised quality of life compared to respondents without these impairments. These data imply strategic community-based health care services, including mental health initiatives, may be indicated for individuals with sensory loss living in underserved regions. Implications for rehabilitation psychology research, service, and policy are discussed as innovations in these areas are needed to better understand and address the disparities that may compromise the overall well-being of residents of underserved communities. (PsycINFO Database Record PMID- 26891248 TI - Neuropsychological functioning, coping, and quality of life among returning war veterans. AB - PURPOSE: The present research tested the hypothesis that action- and emotion focused coping strategies would mediate the relationship between neuropsychological functioning and quality of life among a sample of returning Iraq/Afghanistan veterans. METHOD: Veterans (N = 130) who served as part of the wars in Iraq and Afghanistan completed a diagnostic assessment of PTSD, a battery of questionnaires assessing coping style, traumatic brain injury (TBI), and quality of life, and neuropsychological tests measuring attention, learning and memory, working memory, inhibition, executive control, and visual motor coordination. RESULTS: Executive control, immediate and delayed verbal recall, and visual motor coordination were associated with quality of life. However, after controlling for the effects of combat exposure, PTSD, and probable TBI, no measure of neuropsychological functioning was directly associated with quality of life. Mediation analyses indicated that delayed verbal recall influenced quality of life through its effect on action-focused coping. CONCLUSIONS: Although replication is needed, these findings indicate that delayed verbal recall may indirectly influence quality of life among Iraq/Afghanistan veterans through its association with action-focused coping strategies. Psychologists who are working with veterans that are experiencing memory difficulties and poor quality of life may consider focusing on improving coping skills prior to rehabilitation of memory deficits. (PsycINFO Database Record PMID- 26891251 TI - Multitarget Drugs: an Epigenetic Epiphany. AB - Epigenetics refers to changes in a biological phenotype that are not due to an underlying change in genotype. In eukaryotes, epigenetics involves a set of chemical modifications of the DNA and the histone proteins in nucleosomes. These dynamic changes are carried out by enzymes and modulate protein-protein and protein-nucleic acid interactions to determine whether specific genes are expressed or silenced. Both the epigenetic enzymes and recognition domains are currently important drug discovery targets, particularly for the treatment of cancer. This review summarizes the progress of epigenetic targets that have reached a clinical stage: DNA methyltransferases, histone deacetylases, lysine methyltransferases, lysine demethylases, and bromodomains; this is followed by a comprehensive survey of multitarget drugs that have included an epigenetic target as one of their mechanisms of action. PMID- 26891252 TI - Bismuth(III)dichalcogenones as highly active catalysts in multiple C-C bond formation reactions. AB - Thirteen new bismuth(III) dichalcogenone derivatives of triflates and halides were synthesized and structurally characterized. The mono, di, tetra and heptanuclear complexes were isolated with different bismuth(III) coordination environments. These newly isolated bismuth(III)dichalcogenones were characterized by multinuclear NMR, FT-IR, UV-vis, TGA and single crystal X-ray diffraction techniques. These complexes were tested for the synthesis of symmetrical triaryl- or triheteroarylmethanes and the catalysts were found to be highly active. In particular, the selone complexes were relatively more active than thione complexes. Subsequently, the scope of the catalytic reactions was further explored with different substituents. PMID- 26891254 TI - Mucosal serotonin overflow is associated with colonic stretch rather than phasic contractions. AB - BACKGROUND: Many studies have shown that mucosal serotonin (5-HT) is associated with motility, however, recently there have been some questions to the precise role of this transmitter. The majority of studies have focused on understanding the role of mucosal 5-HT on colonic migratory motor complexes, but very few studies have been carried out to understand how 5-HT release may be associated with other motility patterns. METHODS: Using distal colon segments from C57BL/6J mice, mucosal 5-HT overflow was monitored using amperometry while applying tension in longitudinal or circular directions to stretch the tissue. KEY RESULTS: Phasic and basal 5-HT levels were not associated with the strength of phasic contractions, while being altered using scopolamine and L-NNA. There was a significant increase in mucosal 5-HT with longitudinal and circular muscle stretch. A greater applied force was needed to activate 5-HT release in the circular muscle. In the longitudinal muscle, 5-HT levels increased with stretch until 3 mN, after which the levels returned back to baseline. This stretch-evoked 5-HT overflow was inhibited by transient receptor potential A1 (TRPA1) agonist, 30 MUM ruthenium red in both circular and longitudinal muscle preparations. The decreased 5-HT overflow after 3 mN of tension was reversed using a 5-HT4 antagonist 100 nM GR113808. CONCLUSIONS & INFERENCES: Our findings show a relationship between colonic stretch and mucosal 5-HT overflow, while no relationship is observed with phasic colonic contractions. Such findings provide more insight into the role of mucosal 5-HT in influencing the pattern of colonic motility to diversify fecal propulsion. PMID- 26891253 TI - Prediabetes and diabetes among HIV-infected adults in Cameroon. AB - BACKGROUND: Human immunodeficiency virus (HIV) and certain antiretrovirals are associated with diabetes. Few studies have examined the prevalence of and factors associated with diabetes among HIV-infected individuals on combination antiretroviral therapy (cART) in sub-Saharan Africa; some report prevalence estimates between 3.5-26.5% for diabetes in Cameroon and 20.2-43.5% for prediabetes in sub-Saharan Africa. METHODS: In a cross-sectional study, HIV infected individuals (16-65 years old) were screened for diabetes using haemoglobin A1c (HbA1c ). We further categorized HbA1C as normoglycemia (HbA1c < 5.7%), prediabetes (HbA1c 5.7-6.4%) or diabetes (HbA1c >= 6.5%). Dysglycemia was defined as HbA1c >= 5.7%. Logistic regression modelling was used to assess factors associated with having dysglycemia. RESULTS: Of 500 participants, 363 (72.6%) were female. Median age was 42.5 years [interquartile range (IQR): 36.5 49.5]. Nineteen patients (3.8%) had diabetes and 170 patients (34%) were classified as having prediabetes. One hundred nine (22%) had a CD4+ count <200 cells/mm(3) , and 464 (93%) had received >28 days of ART at time of screening. Median abdominal circumference for women was 79.5 cm (IQR: 75.5-85.3) and for men, 86.5 cm (IQR: 81.7-90.5). Adjusting for age, sex, socio-economic status, CD4 cell count, being on cART >28 days, body mass index, hypertension, history of hypertension, abdominal circumference and duration of HIV infection, larger abdominal circumference was associated with higher prevalence of prediabetes or diabetes (adjusted odds ratio = 1.07, 95% confidence interval: 1.03-1.11), while being on cART (adjusted odds ratio = 0.46, confidence interval: 0.22-0.99) was associated with lower prevalence. CONCLUSIONS: There was a high prevalence of dysglycemia among Cameroonian HIV-infected adults. Larger abdominal circumference was associated with higher prevalence, while cART was associated with lower prevalence. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891250 TI - Finite element models of the human shoulder complex: a review of their clinical implications and modelling techniques. AB - The human shoulder is a complicated musculoskeletal structure and is a perfect compromise between mobility and stability. The objective of this paper is to provide a thorough review of previous finite element (FE) studies in biomechanics of the human shoulder complex. Those FE studies to investigate shoulder biomechanics have been reviewed according to the physiological and clinical problems addressed: glenohumeral joint stability, rotator cuff tears, joint capsular and labral defects and shoulder arthroplasty. The major findings, limitations, potential clinical applications and modelling techniques of those FE studies are critically discussed. The main challenges faced in order to accurately represent the realistic physiological functions of the shoulder mechanism in FE simulations involve (1) subject-specific representation of the anisotropic nonhomogeneous material properties of the shoulder tissues in both healthy and pathological conditions; (2) definition of boundary and loading conditions based on individualised physiological data; (3) more comprehensive modelling describing the whole shoulder complex including appropriate three dimensional (3D) representation of all major shoulder hard tissues and soft tissues and their delicate interactions; (4) rigorous in vivo experimental validation of FE simulation results. Fully validated shoulder FE models would greatly enhance our understanding of the aetiology of shoulder disorders, and hence facilitate the development of more efficient clinical diagnoses, non surgical and surgical treatments, as well as shoulder orthotics and prosthetics. (c) 2016 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd. PMID- 26891256 TI - Fecal Immunochemical Test Versus Fecal Calprotectin for Prediction of Mucosal Healing in Crohn's Disease. AB - BACKGROUND: Mucosal healing (MH) has been proposed as a treatment goal of inflammatory bowel disease patients. We reported recently that not only fecal calprotectin (Fcal) but also the fecal immunochemical test (FIT) can predict MH in ulcerative colitis. However, the predictive power of the fecal markers for MH in Crohn's disease (CD), particularly with small bowel lesions, has not been reported in detail. The aim of this study was to evaluate the predictability of FIT versus Fcal for MH in CD. METHODS: Consecutive CD patients underwent colonoscopy or balloon-assisted enteroscopy according to the disease location. FIT and Fcal were examined using stool samples collected the day before endoscopy. RESULTS: Seventy-one CD patients were analyzed, of whom 42 (59%) underwent balloon-assisted enteroscopy because of the presence of affected lesions in the small intestine. Both the Fcal and the FIT results were significantly correlated with endoscopic activity (r = 0.67 and 0.54, respectively). However, the FIT results did not correlate with the activity in patients with small bowel lesions alone, whereas Fcal did (r = 0.42 versus 0.78). Fcal predicted MH in CD with 87% sensitivity and 71% specificity, whereas the values for FIT were 96% and 48%, respectively. The specificity for MH among patients with small bowel lesions alone was low for FIT (40%) compared with Fcal (80%). CONCLUSIONS: Both FIT and Fcal were correlated with the mucosal status of CD. However, the specificity of FIT was not satisfactory, particularly for small bowel lesions. PMID- 26891255 TI - HLA-C*01 is a Risk Factor for Crohn's Disease. AB - BACKGROUND: A dysregulated mucosal immune response to the intestinal environment in a genetically susceptible host is hypothesized to be critical to the pathogenesis of Crohn's disease (CD). Therefore, we examined CD-susceptibility genes involved in the immune response through a genome-wide association study and consecutive genotyping of human leukocyte antigens (HLAs) and killer cell immunoglobulin-like receptors. METHODS: An initial genome-wide association study was performed with 275 CD patients and 2369 controls from a Korean population. To validate the loci identified in the genome-wide association study, replication genotyping was performed in a different cohort of 242 CD patients and 1066 controls. Finally, high-resolution genotyping of HLA and killer cell immunoglobulin-like receptor was performed. RESULTS: Four susceptibility loci, a promoter region in tumor necrosis factor (ligand) superfamily member (TNFSF15) and 3 independent regions in HLAs, showed significant associations with CD. Among them, rs114985235 in the intergenic region between HLA-B and HLA-C showed the strongest association, with an increased risk of CD (P = 8.71 * 10; odds ratio, 2.25). HLA typing in this region showed HLA-C*01 to be responsible for the association of CD among 43 HLA-B and HLA-C genotypes identified in the Korean population. However, the interaction of HLA-C with killer cell immunoglobulin like receptor had little effect on the development of CD. CONCLUSIONS: We newly identified HLA-C*01 as a prominent CD-susceptibility HLA allotype in the Korean population. In addition, these results confirm that genetic variations in immune response genes, such as HLAs and TNFSF15, are important host factors for the pathogenesis of CD. PMID- 26891257 TI - PDCD4 Deficiency Aggravated Colitis and Colitis-associated Colorectal Cancer Via Promoting IL-6/STAT3 Pathway in Mice. AB - BACKGROUND: Although programmed cell death (PDCD) 4 is generally considered to be a new tumor suppressor, the consequence of Pdcd4 deficiency in tumorigenesis is not well established. The role of PDCD4 in colitis-associated colorectal carcinoma (CRC) remains unknown. METHODS: Experimental colitis and CRC were induced by dextran sodium sulfate and dextran sodium sulfate with azoxymethane, respectively, in wild type and Pdcd4 knockout (Pdcd4(-/-)) mice and were evaluated by clinical examination and histopathology. Levels of cytokines were detected by enzyme-linked immunosorbent assay. Changes in signaling pathways were examined by Western blot and immunofluorescent staining. Cell proliferation was determined by BrdU incorporation and Cell Counting Kit-8 staining. RESULTS: Pdcd4 deficiency not only aggravated the dextran sodium sulfate-induced acute colitis but also promoted the development of colitis-induced CRC. Mechanically, Pdcd4 deficiency accelerated epithelial cell proliferation during tumorigenesis, markedly up-regulated the expression of proinflammatory cytokines, such as interleukin (IL)-6, and enhanced the activation of signal transducer and activator of transcription (STAT3), a IL-6 downstream effector. Using purified cells, we found that Pdcd4 deficiency increased IL-6 expression in vitro and the susceptibility to IL-6/STAT3 pathway-mediated cell proliferation significantly. Furthermore, blockade of IL-6/STAT3 pathway through sgp130Fc reversed the promoting effect of Pdcd4 deficiency on colonic epithelial cell proliferation in vivo. CONCLUSION: The Pdcd4 deficiency accelerates colitis and colitis-associated CRC presumably through up-regulating IL-6/STAT3 pathway, suggesting that PDCD4 plays a protective role in inflammation-associated carcinoma and might be a potential target for the treatment of CRC. PMID- 26891258 TI - Reduced Human alpha-defensin 6 in Noninflamed Jejunal Tissue of Patients with Crohn's Disease. AB - BACKGROUND: Mucosal barrier dysfunction is considered a critical component of Crohn's disease (CD) pathogenesis after the identification of susceptibility genes. However, the precise mechanism underlying mucosal barrier dysfunction has not yet been elucidated. We therefore aimed to elucidate the molecular mechanism underlying the expression of human alpha-defensin 6 (HD6) in patients with CD. METHODS: HD6 expression was induced by the transfection of an atonal homolog 1 (Atoh1) transgene and was assessed by reverse transcription polymerase chain reaction. The HD6 promoter region targeted by Atoh1 and beta-catenin was determined by reporter analysis and chromatin immunoprecipitation assay. HD5/HD6/Atoh1/beta-catenin expression in noninflamed jejunal samples collected by balloon endoscopy from 15 patients with CD and 9 non-inflammatory bowel disease patients were assessed by immunofluorescence. RESULTS: Both promoter activity and gene expression of HD6 was significantly upregulated by the Atoh1 transgene in human colonic cancer cell line. We identified a TCF4 binding site and an E-box site, critical for the regulation of HD6 transcriptional activity by directly binding of Atoh1 in the 200-bp HD6 promoter region. The treatment with beta catenin inhibitor also decreases HD6 promoter activity and gene expression. Moreover, HD6 expression, but not HD5 expression, was found to be decreased in noninflamed jejunal regions from patients with CD. In HD6-negative crypts, nuclear accumulation of beta-catenin was impaired. CONCLUSIONS: HD6 expression was found to be regulated by cooperation between Atoh1 and beta-catenin within the HD6 promoter region. Downregulation of HD6 in noninflamed mucosa may contribute to mucosal barrier dysfunction of patients with CD. PMID- 26891259 TI - Clostridium Difficile Infection in Ulcerative Colitis: Can Alteration of the Gut associated Microbiome Contribute to Pouch Failure? AB - BACKGROUND: Ulcerative colitis is frequently treated with total proctocolectomy and ileal pouch-anal anastomosis reconstruction. Causes of pouch failure and criteria for improved patient selection remain poorly understood. We aimed to identify risk factors for pouch failure. METHODS: We performed a retrospective chart review of patients in a prospectively maintained database. Consecutive patients undergoing ileal pouch-anal anastomosis for inflammatory bowel disease between 2000 and 2010 at our institution were included. The primary outcome was pouch failure, defined as permanent ostomy diversion or pouch excision. RESULTS: Of 417 total patients, 28 (6.7%) patients developed pouch failure. Pouch failure was associated with female gender, anastomotic leak, Crohn's disease of the pouch and preoperative Clostridium difficile colitis. The use of anti-tumor necrosis factor alpha biologics was not associated with pouch failure. Notably, 14.9% of patients were diagnosed with preoperative C. difficile colitis, a factor independently associated with pouch failure (hazard ratio 3.02; 95% confidence interval, 1.23-7.44; P = 0.016). C. difficile colitis did not contribute to failure by increasing the incidence of anastomotic leak but was associated with a diagnosis of Crohn's disease of the pouch (adjusted hazard ratio 2.27 [1.08 4.79]; P = 0.031). Anastomotic leak (P < 0.001) and pelvic abscess requiring drainage (P = 0.031) were other independent risk factors for pouch failure. CONCLUSIONS: In addition to previously known risk factors, history of preoperative C. difficile colitis was associated with pouch failure after reconstruction, suggesting the need for further study into the role of the gut associated microbiome in pouch outcomes. PMID- 26891262 TI - Editorial. PMID- 26891261 TI - How to Diagnose and Treat IBD Mimics in the Refractory IBD Patient Who Does Not Have IBD. AB - Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and includes both Crohn's disease and ulcerative colitis. Patients with IBD often present with abdominal pain, diarrhea, and rectal bleeding but may also have a wide variety of other symptoms such as weight loss, fever, nausea, vomiting, and possibly obstruction. Given that the presentation of IBD is not specific, the differential diagnosis is broad and encompasses a wide spectrum of diseases, many of which can mimic and/or even coexist with IBD. It is important for physicians to differentiate symptoms due to refractory IBD from symptoms due to IBD mimics when a patient is not responding to standard IBD treatment. Many of the various IBD mimics include infectious etiologies (viral, bacterial, mycobacterial, fungal, protozoal, and helminthic infections), vascular causes, other immune causes including autoimmune etiologies, drug-induced processes, radiation-induced, and other etiologies such as small intestinal bacterial overgrowth, diverticulitis, and bile acid malabsorption. Thoughtful consideration and evaluation of these potential etiologies through patient history and physical examination, as well as appropriate tests, endoscopic evaluation, and cross-sectional imaging is required to evaluate any patient presenting with symptoms consistent with IBD. PMID- 26891263 TI - Identification of by-products in support of process development of Muraglitazar. PMID- 26891260 TI - Inhibition of Interleukin-10 Signaling Induces Microbiota-dependent Chronic Colitis in Apolipoprotein E Deficient Mice. AB - BACKGROUND: Apolipoprotein E (ApoE) mediates potent antiinflammatory and immunomodulatory properties in addition to its roles in regulating cholesterol transport and metabolism. However, its role in the intestine, specifically during inflammation, is largely unknown. METHODS: Mice (C57BL/6 or ApoE-deficient [ApoE KO] mice) were administered either single or 4 injections (weekly) of anti interleukin (IL)-10 receptor monoclonal antibody (1.0 mg/mouse; intraperitoneally) and euthanized 1 week after the last injection. 16S rRNA sequencing was performed in fecal samples to analyze the gut bacterial load and its composition. Microbiota was ablated by administration of broad-spectrum antibiotics in drinking water. IL-10KO mice were cohoused with ApoE-KO mice or their wild-type littermates to monitor the colitogenic potential of gut microbiota harbored in ApoE-KO mice. RESULTS: ApoE-KO mice developed severe colitis upon neutralization of IL-10 signaling as assessed by every parameter analyzed. 16S rRNA sequencing revealed that the ApoE-KO mice display elevated and altered gut microbiota that were accompanied with impaired production of intestinal antimicrobial peptides. Interestingly, microbiota ablation ameliorates colitis development in ApoE-KO mice. Exacerbated and accelerated colitis was observed in IL-10KO mice when cohoused with ApoE-KO mice. CONCLUSIONS: Our study highlights a novel interplay between ApoE and IL-10 in maintaining gut homeostasis and that such crosstalk may play a critical role in the pathogenesis of inflammatory bowel disease. Gut sterilization and the cohousing experiment suggest that microbiota play a pivotal role in the development of inflammatory bowel disease in mice lacking ApoE. PMID- 26891265 TI - Intraoperative transconjunctival mitomycin-C application for needle revision of trabeculectomy. PMID- 26891264 TI - No Interaction with Alcohol Consumption, but Independent Effect of C12orf51 (HECTD4) on Type 2 Diabetes Mellitus in Korean Adults Aged 40-69 Years: The KoGES_Ansan and Ansung Study. AB - Previously, genetic polymorphisms of C12orf51 (HECTD4) (rs2074356 and/or rs11066280) have been shown to be related to alcohol consumption and type 2 diabetes (T2D). This study aimed to prospectively examine whether C12orf51 had an interaction with or independent effect on alcohol consumption and the risk of T2D. The present study included 3,244 men and 3,629 women aged 40 to 69 years who participated in the Korean Genome and Epidemiology Study (KoGES)_Ansan and Ansung Study. Cox proportional hazards models were used to estimate HRs and 95% CIs for T2D. rs2074356 and rs11066280 were associated with the risk of T2D after adjusting for alcohol consumption (rs2074356 for AA: HR = 0.39 and 95% CI = 0.17 0.87 in men, and HR = 0.36 and 95% CI = 0.13-0.96 in women; rs11066280 for AA: HR = 0.44 and 95% CI = 0.23-0.86 in men, and HR = 0.39 and 95% CI = 0.16-0.94 in women). We identified that the association of each variant (rs2074356 and rs11065756) in C12orf51 was nearly unchanged after adjusted for alcohol consumption. Therefore, the association of 2 SNPs in C12orf51 with diabetes may not be mediated by alcohol use. There was no interaction effect between alcohol consumption and the SNPs with T2D. However, even in never-drinkers, minor allele homozygote strongly influenced T2D risk reduction (rs2074356 for AA: HR = 0.35, 95% CI = 0.14-0.90, and p-trend = 0.0035 in men and HR = 0.34, 95% CI = 0.13 0.93, and p-trend = 0.2348 in women; rs11066280 for AA: HR = 0.36, 95% CI = 0.16 0.82, and p-trend = 0.0014 in men and HR = 0.39, 95% CI = 0.16-0.95, and p-trend = 0.3790 in women), while alcohol consumption did not influence the risk of T2D within each genotype. rs2074356 and rs11066280 in or near C12orf51, which is related to alcohol drinking behavior, may longitudinally decrease the risk of T2D, but not through regulation of alcohol consumption. PMID- 26891267 TI - Matrix metalloprotease activity shapes the magnitude of EPSPs and spike plasticity within the hippocampal CA3 network. PMID- 26891269 TI - Multi-pollutant exposure profiles associated with term low birth weight in Los Angeles County. AB - Research indicates that multiple outdoor air pollutants and adverse neighborhood conditions are spatially correlated. Yet health risks associated with concurrent exposure to air pollution mixtures and clustered neighborhood factors remain underexplored. Statistical models to assess the health effects from pollutant mixtures remain limited, due to problems of collinearity between pollutants and area-level covariates, and increases in covariate dimensionality. Here we identify pollutant exposure profiles and neighborhood contextual profiles within Los Angeles (LA) County. We then relate these profiles with term low birth weight (TLBW). We used land use regression to estimate NO2, NO, and PM2.5 concentrations averaged over census block groups to generate pollutant exposure profile clusters and census block group-level contextual profile clusters, using a Bayesian profile regression method. Pollutant profile cluster risk estimation was implemented using a multilevel hierarchical model, adjusting for individual-level covariates, contextual profile cluster random effects, and modeling of spatially structured and unstructured residual error. Our analysis found 13 clusters of pollutant exposure profiles. Correlations between study pollutants varied widely across the 13 pollutant clusters. Pollutant clusters with elevated NO2, NO, and PM2.5 concentrations exhibited increased log odds of TLBW, and those with low PM2.5, NO2, and NO concentrations showed lower log odds of TLBW. The spatial patterning of pollutant cluster effects on TLBW, combined with between-pollutant correlations within pollutant clusters, imply that traffic-related primary pollutants influence pollutant cluster TLBW risks. Furthermore, contextual clusters with the greatest log odds of TLBW had more adverse neighborhood socioeconomic, demographic, and housing conditions. Our data indicate that, while the spatial patterning of high-risk multiple pollutant clusters largely overlaps with adverse contextual neighborhood cluster, both contribute to TLBW while controlling for the other. PMID- 26891268 TI - Ingression Progression Complexes Control Extracellular Matrix Remodelling during Cytokinesis in Budding Yeast. AB - Eukaryotic cells must coordinate contraction of the actomyosin ring at the division site together with ingression of the plasma membrane and remodelling of the extracellular matrix (ECM) to support cytokinesis, but the underlying mechanisms are still poorly understood. In eukaryotes, glycosyltransferases that synthesise ECM polysaccharides are emerging as key factors during cytokinesis. The budding yeast chitin synthase Chs2 makes the primary septum, a special layer of the ECM, which is an essential process during cell division. Here we isolated a group of actomyosin ring components that form complexes together with Chs2 at the cleavage site at the end of the cell cycle, which we named 'ingression progression complexes' (IPCs). In addition to type II myosin, the IQGAP protein Iqg1 and Chs2, IPCs contain the F-BAR protein Hof1, and the cytokinesis regulators Inn1 and Cyk3. We describe the molecular mechanism by which chitin synthase is activated by direct association of the C2 domain of Inn1, and the transglutaminase-like domain of Cyk3, with the catalytic domain of Chs2. We used an experimental system to find a previously unanticipated role for the C-terminus of Inn1 in preventing the untimely activation of Chs2 at the cleavage site until Cyk3 releases the block on Chs2 activity during late mitosis. These findings support a model for the co-ordinated regulation of cell division in budding yeast, in which IPCs play a central role. PMID- 26891270 TI - Time trends of perfluorinated alkyl acids in serum from Danish pregnant women 2008-2013. AB - We aimed to estimate the levels and time trends of perfluorinated alkyl acids (PFAAs) in serum of 1533 Danish pregnant nulliparous women between 2008 and 2013. The selection criterion of only including nulliparous women was chosen to avoid confounding from parity. The serum samples were analyzed for sixteen PFAAs using solid phase extraction and liquid chromatography tandem mass spectrometry (LC MS/MS). We investigated the time trends for seven PFAAs, which were detected in more than 50% of the samples: perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnA). We found that the serum levels of all seven PFAAs decreased during the period from 2008 to 2013; on average PFHxS decreased with 7.0% per year, PFHpS with 14.8%, PFOS with 9.3%, PFOA with 9.1%, PFNA with 6.2%, PFDA with 6.3%, and PFUnA with 7.1% per year. Adjustment for maternal age, body mass index (BMI), educational level and gestational age at blood sampling did not change the time trends much. To our knowledge, we are the first to report decreasing trends of PFNA, PFDA and PFUnA since year 2000, thereby indicating that the phase-out of these compounds are beginning to show an effect on human serum levels. PMID- 26891271 TI - Chronic liquid nutrition feeding affects blood pressure, heart and kidney morphology, and serum lipid profile in Wistar rats. AB - We determined the effect of chronic liquid nutrition (Fresubin) intake in different developmental stages on the cardiovascular and renal system of male Wistar rats. Body weight, water intake and blood pressure were periodically measured. Selected serum and urine biochemical parameters reflecting metabolic and homeostatic changes after Fresubin intake were investigated as well. Heart and kidney weight, diameter of cardiomyocytes, diameter and length of cardiomyocyte nuclei, wall thickness of thoracic aorta, the diameter and the area of renal corpuscles and serum and urine biochemical parameters were assessed at the end of experiment. We showed that Fresubin intake differently affects the investigated morphological and biochemical parameters in rats and this effect was dependent on the developmental stage when Fresubin was provided. Importantly, we have shown that Fresubin-induced elevation of blood pressure is a reversible phenomenon and it is independent of weight gain and subsequent development of obesity. PMID- 26891272 TI - Sonodynamic therapy induces apoptosis of human leukemia HL-60 cells in the presence of protoporphyrin IX. AB - Sonodynamic therapy (SDT) is expected to be a novel therapeutic strategy for tumor. The protoporphyrin IX disodium salt (PpIX), a photosensitizer, can be activated by ultrasound. The present study aims to investigate apoptosis of HL-60 cells induced by PpIX-mediated SDT. 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was adopted to examine cell toxicity. Apoptosis was detected using Annexin V-PE/7-amino-actinomycin D (7-AAD) double staining. Detection of apoptotic bodies was examined by Hoechst33342 (HO) staining. Western blotting was used to analyze the protein of caspase-3 and poly ADP-ribose polymerase (PARP). Intracellular reactive oxygen species (ROS) was detected by a flow cytometer after exposures. Compared with PpIX alone and ultrasound alone groups, the synergistic cytotoxicity of PpIX plus ultrasound were significantly boosted. In addition, as determined by Annexin V-PE/7-AAD staining, SDT significantly induced HL-60 cell apoptosis, the obvious nuclear condensation was also found with HO staining at 4 hours post-SDT treatment. Furthermore, Western blotting showed visible enhancement of caspase-3 and PARP cleavage in this process. Besides, intracellular ROS production was significantly enhanced after SDT. Our findings demonstrate that PpIX-mediated SDT could induce apoptosis on HL 60 cells, suggesting that apoptosis is an important mechanism of cell death induced by PpIX-mediated SDT. PMID- 26891273 TI - beta-Adrenergic signaling in rat heart is similarly affected by continuous and intermittent normobaric hypoxia. AB - Chronic hypoxia may produce a cardioprotective phenotype characterized by increased resistance to ischemia-reperfusion injury. Nevertheless, the molecular basis of cardioprotective effects of hypoxia is still not quite clear. The present study investigated the consequences of a 3-week adaptation to cardioprotective (CNH, continuous normobaric hypoxia) and nonprotective (INH, intermittent normobaric hypoxia; 23 h/day hypoxia followed by 1 h/day reoxygenation) regimen of hypoxia on beta-adrenergic signaling in the rat myocardium. Both regimens of hypoxia lowered body weight and led to marked right ventricular (RV) hypertrophy, which was accompanied by 25% loss of beta1 adrenergic receptors (beta1-ARs) in the RV. No significant changes were found in beta-ARs in left ventricular (LV) preparations from animals adapted to hypoxia. Although adenylyl cyclase (AC) activity stimulated through the G proteins was decreased in the RV and increased in the LV after exposure to hypoxia, there were no significant changes in the expression of the dominant myocardial AC 5/6 isoforms and the stimulatory G proteins. These data suggest that chronic normobaric hypoxia may strongly affect myocardial beta-adrenergic signaling but adaptation to cardioprotective and nonprotective regimens of hypoxia does not cause notably diverse changes. PMID- 26891275 TI - Comparative analysis of mesenchymal stromal cells from different tissue sources in respect to articular cartilage tissue engineering. AB - The main goal of this study was a comparison of biological properties of mesenchymal stromal cells (MSCs) obtained from bone marrow, adipose tissue and umbilical cord with respect to articular cartilage regeneration. MSCs were isolated and expanded in vitro up to the third passage. The kinetics of proliferation was analyzed by cell analyzer CEDEX XS and expression of selected markers was assessed by flow cytometry. The morphology was analyzed by inverted microscope and TEM. Pellet culture system and chondrogenic medium containing TGF beta1 was used to induce chondrogenic differentiation. Chondrogenesis was analyzed by real-time PCR; the expression of collagen type I and type II was compared. MSCs from all sources showed similar kinetics of proliferation and shared expression of CD73, CD90 and CD105; and were negative for CD14, CD20, CD34 and CD45. Observation under inverted microscope and TEM showed similar morphology of all analyzed MSCs. Cells from all sources underwent chondrogenic differentiation - they expressed collagen type II and acid mucopolysaccharides typical for hyaline cartilage. On the basis of obtained results it should be emphasized that MSCs from bone marrow, adipose tissue and umbilical cord share biological properties. They possess the chondrogenic potential and may be utilized in cartilage tissue engineering. PMID- 26891274 TI - Photoactivated hypericin is not genotoxic. AB - The study was designed to test the potential photogenotoxicity of hypericin (HYP) at three different levels: primary DNA damages, gene mutations and chromosome aberrations. Primary genetic changes were detected using the comet assay. The potential mutagenic activity of HYP was assessed using the Ames/Salmonella typhimurium assay. Finally, the ability of photoactivated HYP to induce chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test and compared to that of non-photoactivated HYP. The results have shown that photoactivated HYP can only induce primary DNA damages (single-strand DNA breaks), acting in a dose-response manner. This activity depended both on HYP concentrations and an intensity of the light energy needed for its photoactivation. However, mutagenic effect of photoactivated HYP evaluated in the Ames assay using three bacterial strains S. typhimurium (TA97, TA98 and TA100) was not confirmed. Moreover, photoactivated HYP in the range of concentrations (0.005-0.01 ug/ml) was not found to be clastogenic against HepG2 cells. Our findings from both the Ames assay and the chromosome aberrations test provide evidence that photoactivated HYP is not genotoxic, which might be of great importance mainly in terms of its use in the photodynamic therapy. PMID- 26891276 TI - Selective Inhibition of Aggregation and Toxicity of a Tau-Derived Peptide using Its Glycosylated Analogues. AB - Protein glycosylation is a ubiquitous post-translational modification that regulates the folding and function of many proteins. Misfolding of protein monomers and their toxic aggregation are the hallmark of many prevalent diseases. Thus, understanding the role of glycans in protein aggregation is highly important and could contribute both to unraveling the pathology of protein misfolding diseases as well as providing a means for modifying their course for therapeutic purposes. Using beta-O-linked glycosylated variants of the highly studied Tau-derived hexapeptide motif VQIVYK, which served as a simplified amyloid model, we demonstrate that amyloid formation and toxicity can be strongly attenuated by a glycan unit, depending on the nature of the glycan itself. Importantly, we show for the first time that not only do glycans hinder self aggregation, but the glycosylated peptides are capable of inhibiting aggregation of the non-modified corresponding amyloid scaffold. PMID- 26891277 TI - Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy. AB - Fibroblast growth factor homologous factors (FHFs) belong to the fibroblast growth factor (FGF) superfamily, which plays an important role in prostate cancer (PCa). Mining of public database suggests that FGF13 (FHF2) mRNA expression is altered in over 30% of PCa cases. This study examined the FGF13 expression pattern in human PCa specimens and evaluated its potential as a biomarker for patient outcome after radical prostatectomy (RP). Immunohistochemistry (IHC) showed that FGF13 was detectable in the majority of human PCa samples, and FGF13 IHC scores were higher in high-grade prostatic intraepithelial neoplasia, in primary PCa and in metastatic PCa than in benign prostatic tissue. There was a significant association between high cytoplasmic FGF13 staining and a risk of biochemical recurrence (BCR) after RP. This was also evident in the intermediate to high-risk patient groups. In contrast, positive nuclear FGF13 staining along with low cytoplasmic FGF13 group showed a decreased BCR risk. Multivariate regression analysis indicated that high cytoplasmic FGF13 staining was associated with BCR and that this could serve as an independent prognostic marker in PCa. Several PCa cell lines showed increased FGF13 expression at the mRNA and protein levels compared to the immortalized prostate epithelial cell line PNT1a. Analysis of co-labeled cells suggested a possible interaction of FGF13 with alpha-tubulin and the voltage-gated sodium channel proteins (Na(V)s/VGSCs). Our data indicate that, for PCa patients after RP, FGF13 serves as a potential novel prognostic marker that improves prediction of BCR-free survival, in particular if combined with other clinical parameters. PMID- 26891278 TI - Use of Galvanic Skin Responses, Salivary Biomarkers, and Self-reports to Assess Undergraduate Student Performance During a Laboratory Exam Activity. AB - Typically, self-reports are used in educational research to assess student response and performance to a classroom activity. Yet, addition of biological and physiological measures such as salivary biomarkers and galvanic skin responses are rarely included, limiting the wealth of information that can be obtained to better understand student performance. A laboratory protocol to study undergraduate students' responses to classroom events (e.g., exams) is presented. Participants were asked to complete a representative exam for their degree. Before and after the laboratory exam session, students completed an academic achievement emotions self-report and an interview that paralleled these questions when participants wore a galvanic skin sensor and salivary biomarkers were collected. Data collected from the three methods resulted in greater depth of information about students' performance when compared to the self-report. The work can expand educational research capabilities through more comprehensive methods for obtaining nearer to real-time student responses to an examination activity. PMID- 26891279 TI - Copper(II)-catalyzed C5 and C7 halogenation of quinolines using sodium halides under mild conditions. AB - A simple and mild protocol for copper catalyzed halogenation of quinoline at C5 and C7 positions was developed, affording the desired remote C-H activation products in moderate to good yields. This reaction proceeds with low-cost sodium halides (NaX, X = Cl, Br, I) and features excellent substrate tolerance. A series of control experiments were carried out to illustrate a single-electron-transfer process which plays a vital role in the halogenation. PMID- 26891280 TI - Reply to Comment on: The UK Experience of a Treatment Strategy for Pediatric Metastatic Medulloblastoma Comprising Intensive Induction Chemotherapy, Hyperfractionated Accelerated Radiotherapy, and Response-Directed High-Dose Myeloablative Chemotherapy or Maintenance Chemotherapy (Milan Strategy). PMID- 26891282 TI - Synthesis of Cd-free InP/ZnS Quantum Dots Suitable for Biomedical Applications. AB - Fluorescent nanocrystals, specifically quantum dots, have been a useful tool for many biomedical applications. For successful use in biological systems, quantum dots should be highly fluorescent and small/monodisperse in size. While commonly used cadmium-based quantum dots possess these qualities, they are potentially toxic due to the possible release of Cd(2+) ions through nanoparticle degradation. Indium-based quantum dots, specifically InP/ZnS, have recently been explored as a viable alternative to cadmium-based quantum dots due to their relatively similar fluorescence characteristics and size. The synthesis presented here uses standard hot-injection techniques for effective nanoparticle growth; however, nanoparticle properties such as size, emission wavelength, and emission intensity can drastically change due to small changes in the reaction conditions. Therefore, reaction conditions such temperature, reaction duration, and precursor concentration should be maintained precisely to yield reproducible products. Because quantum dots are not inherently soluble in aqueous solutions, they must also undergo surface modification to impart solubility in water. In this protocol, an amphiphilic polymer is used to interact with both hydrophobic ligands on the quantum dot surface and bulk solvent water molecules. Here, a detailed protocol is provided for the synthesis of highly fluorescent InP/ZnS quantum dots that are suitable for use in biomedical applications. PMID- 26891283 TI - Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4 Hydroxyproline. AB - A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB 231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 umol/L). PMID- 26891281 TI - An enzymatic deconjugation method for the analysis of small molecule active drugs on antibody-drug conjugates. AB - Antibody-drug conjugates (ADCs) are complex therapeutic agents that use the specific targeting properties of antibodies and the highly potent cytotoxicity of small molecule drugs to selectively eliminate tumor cells while limiting the toxicity to normal healthy tissues. Two critical quality attributes of ADCs are the purity and stability of the active small molecule drug linked to the ADC, but these are difficult to assess once the drug is conjugated to the antibody. In this study, we report a enzyme deconjugation approach to cleave small molecule drugs from ADCs, which allows the drugs to be subsequently characterized by reversed-phase high performance liquid chromatography. The model ADC we used in this study utilizes a valine-citrulline linker that is designed to be sensitive to endoproteases after internalization by tumor cells. We screened several proteases to determine the most effective enzyme. Among the 3 cysteine proteases evaluated, papain had the best efficiency in cleaving the small molecule drug from the model ADC. The deconjugation conditions were further optimized to achieve complete cleavage of the small molecule drug. This papain deconjugation approach demonstrated excellent specificity and precision. The purity and stability of the active drug on an ADC drug product was evaluated and the major degradation products of the active drug were identified. The papain deconjugation method was also applied to several other ADCs, with the results suggesting it could be applied generally to ADCs containing a valine-citrulline linker. Our results indicate that the papain deconjugation method is a powerful tool for characterizing the active small molecule drug conjugated to an ADC, and may be useful in ensuring the product quality, efficacy and the safety of ADCs. PMID- 26891284 TI - Constructing a MoS2 QDs/CdS Core/Shell Flowerlike Nanosphere Hierarchical Heterostructure for the Enhanced Stability and Photocatalytic Activity. AB - MoS2 quantum dots (QDs)/CdS core/shell nanospheres with a hierarchical heterostructure have been prepared by a simple microwave hydrothermal method. The as-prepared samples are characterized by XRD, TEM, SEM, UV-VIS diffuse reflectance spectra (DRS) and N2-sorption in detail. The photocatalytic activities of the samples are evaluated by water splitting into hydrogen. Results show that the as-prepared MoS2 QDs/CdS core/shell nanospheres with a diameter of about 300 nm are composed of the shell of CdS nanorods and the core of MoS2 QDs. For the photocatalytic reaction, the samples exhibit a high stability of the photocatalytic activity and a much higher hydrogen evolution rate than the pure CdS, the composite prepared by a physical mixture, and the Pt-loaded CdS sample. In addition, the stability of CdS has also been greatly enhanced. The effect of the reaction time on the formations of nanospheres, the photoelectric properties and the photocatalytic activities of the samples has been investigated. Finally, a possible photocatalytic reaction process has also been proposed. PMID- 26891285 TI - Synthesis, Molecular Structure Optimization, and Cytotoxicity Assay of a Novel 2 Acetyl-3-amino-5-[(2-oxopropyl)sulfanyl]-4-cyanothiophene. AB - A novel thiophene-containing compound, 2-acetyl-3-amino-5-[(2-oxopropyl)sulfanyl] 4-cyanothiophene (4) was synthesized by reaction of malononitrile with CS2 in the presence of K2CO3 under reflux in DMF and the subsequent reaction with chloroacetone followed by cyclization. This compound has been characterized by means of FT-IR, 1H-NMR, (13)C-NMR, and mass spectrometry as well as elemental analysis. In addition, the molecular structures of compound 4 was determined by X ray crystallography. The geometry of the molecule is stabilized by an intramolecular interaction between N1-H1...O1 to form S6 graf set ring motif. In the crystal, molecules are linked via N1-H2...O1 and C7-H7A...N2 interactions to form a three-dimensional network. Molecular structure and other spectroscopic properties of compound 4 were calculated using DFT B3LYP/6-31G (d,p) method. Results revealed a good agreement between the optimized geometric parameters and the observed X-ray structure. Furthermore, and by employing the natural bond orbital (NBO) method, the intramolecular charge transfer (ICT) interactions along with natural atomic charges at different sites, were calculated; results indicated strong n->pi* ICT from LP(1)N5->BD*(2)C15-C16 (63.23 kcal/mol). In addition, the stabilization energy E(2) of the LP(2)O3-> BD*(1)N5-H6 ICT (6.63 kcal/mol) indicated the presence of intramolecular N-H...OH bonding. Similarly, calculations of the electronic spectra of compound 4 using, TD-DFT revealed a good agreement with the experimental data. Finally, compound 4 was evaluated for its in vitro cytotoxic effect against PC-3 and HeLa cell lines, as an anticancer agent, and found to be nontoxic. PMID- 26891286 TI - Inhibition of CYP2B6 by Medicinal Plant Extracts: Implication for Use of Efavirenz and Nevirapine-Based Highly Active Anti-Retroviral Therapy (HAART) in Resource-Limited Settings. AB - Highly active antiretroviral therapy (HAART) has greatly improved health parameters of HIV infected individuals. However, there are several challenges associated with the chronic nature of HAART administration. For populations in health transition, dual use of medicinal plant extracts and conventional medicine poses a significant challenge. There is need to evaluate interactions between commonly used medicinal plant extracts and antiretroviral drugs used against HIV/AIDS. Efavirenz (EFV) and nevirapine (NVP) are the major components of HAART both metabolized by CYP2B6, an enzyme that can potentially be inhibited or induced by compounds found in medicinal plant extracts. The purpose of this study was to evaluate the effects of extracts of selected commonly used medicinal plants on CYP2B6 enzyme activity. Recombinant human CYP2B6 was used to evaluate inhibition, allowing the assessment of herb-drug interactions (HDI) of medicinal plants Hyptis suaveolens, Myrothamnus flabellifolius, Launaea taraxacifolia, Boerhavia diffusa and Newbouldia laevis. The potential of these medicinal extracts to cause HDI was ranked accordingly for reversible inhibition and also classified as potential time-dependent inhibitor (TDI) candidates. The most potent inhibitor for CYP2B6 was Hyptis suaveolens extract (IC50 = 19.09 +/- 1.16 ug/mL), followed by Myrothamnus flabellifolius extract (IC50 = 23.66 +/- 4.86 ug/mL), Launaea taraxacifolia extract (IC50 = 33.87 +/- 1.54 ug/mL), and Boerhavia diffusa extract (IC50 = 34.93 +/- 1.06 ug/mL). Newbouldia laevis extract, however, exhibited weak inhibitory effects (IC50 = 100 +/- 8.71 ug/mL) on CYP2B6. Launaea taraxacifolia exhibited a TDI (3.17) effect on CYP2B6 and showed a high concentration of known CYP450 inhibitory phenolic compounds, chlorogenic acid and caffeic acid. The implication for these observations is that drugs that are metabolized by CYP2B6 when co-administered with these herbal medicines and when adequate amounts of the extracts reach the liver, there is a high likelihood of standard doses affecting drug plasma concentrations which could lead to toxicity. PMID- 26891287 TI - Molecular and Functional Characterization of FLOWERING LOCUS T Homologs in Allium cepa. AB - Onion bulbing is an important agricultural trait affecting economic value and is regulated by flowering-related genes. FLOWERING LOCUS T (FT)-like gene function is crucial for the initiation of flowering in various plant species and also in asexual reproduction in tuber plants. By employing various computational analysis using RNA-Seq data, we identified eight FT-like genes (AcFT) encoding PEBP (phosphatidylethanolamine-binding protein) domains in Allium cepa. Sequence and phylogenetic analyses of FT-like proteins revealed six proteins that were identical to previously reported AcFT1-6 proteins, as well as one (AcFT7) with a highly conserved region shared with AcFT6 and another (comp106231) with low similarity to MFT protein, but containing a PEBP domain. Homology modelling of AcFT7 proteins showed similar structures and conservation of amino acids crucial for function in AtFT (Arabidopsis) and Hd3a (rice), with variation in the C terminal region. Further, we analyzed AcFT expression patterns in different transitional stages, as well as under SD (short-day), LD (long-day), and drought treatment in two contrasting genotypic lines EM (early maturation, 36101) and LM (late maturation, 36122). The FT transcript levels were greatly affected by various environmental factors such as photoperiod, temperature and drought. Our results suggest that AcFT7 is a member of the FT-like genes in Allium cepa and may be involved in regulation of onion bulbing, similar to other FT genes. In addition, AcFT4 and AcFT7 could be involved in establishing the difference in timing of bulb maturity between the two contrasting onion lines. PMID- 26891288 TI - Comparison of Properties among Dendritic and Hyperbranched Poly(ether ether ketone)s and Linear Poly(ether ketone)s. AB - Poly(ether ether ketone) dendrimers and hyperbranched polymers were prepared from 3,5-dimethoxy-4'-(4-fluorobenzoyl)diphenyl ether and 3,5-dihydroxy-4'-(4 fluorobenzoyl)diphenyl ether through aromatic nucleophilic substitution reactions. 1-(tert-Butyldimethylsiloxy)-3,5-bis(4-fluorobenzoyl)benzene was polycondensed with bisphenols, followed by cleavage of the protective group to form linear poly(ether ketone)s having the same hydroxyl groups in the side chains as the chain ends of the dendrimer and hyperbranched polymers. Their properties, such as solubilities, reduced viscosities, and thermal properties, were compared with one another. Similar comparisons were also carried out among the corresponding methoxy group polymers, and the size of the molecules was shown to affect the properties. PMID- 26891289 TI - Focus on Chirality of HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors. AB - Chiral HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are of great interest since one enantiomer is often more potent than the corresponding counterpart against the HIV-1 wild type (WT) and the HIV-1 drug resistant mutant strains. This review exemplifies the various studies made to investigate the effect of chirality on the antiretroviral activity of top HIV-1 NNRTI compounds, such as nevirapine (NVP), efavirenz (EFV), alkynyl- and alkenylquinazolinone DuPont compounds (DPC), diarylpyrimidine (DAPY), dihydroalkyloxybenzyloxopyrimidine (DABO), phenethylthiazolylthiourea (PETT), indolylarylsulfone (IAS), arylphosphoindole (API) and trifluoromethylated indole (TFMI) The chiral separation, the enantiosynthesis, along with the biological properties of these HIV-1 NNRTIs, are discussed. PMID- 26891290 TI - Bioactive ZnO Coatings Deposited by MAPLE-An Appropriate Strategy to Produce Efficient Anti-Biofilm Surfaces. AB - Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections. PMID- 26891291 TI - MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion. AB - This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR 9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 beta (GSK3beta), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5 mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3beta, ATP8A2, and EIF4EBP1, respectively. PMID- 26891292 TI - Herbal Medicine in Mexico: A Cause of Hepatotoxicity. A Critical Review. AB - In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products. PMID- 26891293 TI - Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer. AB - Non-small cell lung cancer (NSCLC) represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs) negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations. PMID- 26891294 TI - The Chinese Herbal Medicine Formula mKG Suppresses Pulmonary Fibrosis of Mice Induced by Bleomycin. AB - Pulmonary fibrosis (PF) is a serious progressive lung disease and it originates from inflammation-induced parenchymal injury with excessive extracellular matrix deposition to result in the destruction of the normal lung architecture. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicine, has a prominent anti-inflammatory effect. The present study is to explore the inhibitory effects of mKG on bleomycin (BLM)-induced pulmonary fibrosis in mice. mKG significantly decreased pulmonary alveolitis, fibrosis scores, and interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-beta (TGF-beta) and hydroxyproline (HYP) levels in lung tissue of mice compared with BLM treatment. It markedly alleviated the increase of HYP content in the lung tissues and pathologic changes of pulmonary fibrosis caused by BLM instillation. In conclusion, mKG has an anti-fibrotic effect and might be employed as a therapeutic candidate agent for attenuating pulmonary fibrosis. PMID- 26891295 TI - Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms. AB - In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress-induced GC resistance in human macrophage-like cells. Cells were pre-treated with H2O2 (800 uM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2',7'-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect. PMID- 26891298 TI - Enhanced ICP for the Registration of Large-Scale 3D Environment Models: An Experimental Study. AB - One of the main applications of mobile robots is the large-scale perception of the outdoor environment. One of the main challenges of this application is fusing environmental data obtained by multiple robots, especially heterogeneous robots. This paper proposes an enhanced iterative closest point (ICP) method for the fast and accurate registration of 3D environmental models. First, a hierarchical searching scheme is combined with the octree-based ICP algorithm. Second, an early-warning mechanism is used to perceive the local minimum problem. Third, a heuristic escape scheme based on sampled potential transformation vectors is used to avoid local minima and achieve optimal registration. Experiments involving one unmanned aerial vehicle and one unmanned surface vehicle were conducted to verify the proposed technique. The experimental results were compared with those of normal ICP registration algorithms to demonstrate the superior performance of the proposed method. PMID- 26891296 TI - Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis. AB - MicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP), while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor kappa-B ligand (RANKL) predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET) technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP. PMID- 26891299 TI - Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning. AB - A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called "MSG preconditioning". However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID- 26891297 TI - Atypical Antipsychotics in the Treatment of Acute Bipolar Depression with Mixed Features: A Systematic Review and Exploratory Meta-Analysis of Placebo-Controlled Clinical Trials. AB - Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD -0.74, 95% CI -1.20 to -0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery-Asberg Depression Rating Scale (MADRS) scores (SMD -1.08, 95% CI -1.35 to -0.81, p < 0.001) vs. placebo (n = 678). Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and clinically definitive conclusions. PMID- 26891300 TI - A Collaborative Secure Localization Algorithm Based on Trust Model in Underwater Wireless Sensor Networks. AB - Localization is one of the hottest research topics in Underwater Wireless Sensor Networks (UWSNs), since many important applications of UWSNs, e.g., event sensing, target tracking and monitoring, require location information of sensor nodes. Nowadays, a large number of localization algorithms have been proposed for UWSNs. How to improve location accuracy are well studied. However, few of them take location reliability or security into consideration. In this paper, we propose a Collaborative Secure Localization algorithm based on Trust model (CSLT) for UWSNs to ensure location security. Based on the trust model, the secure localization process can be divided into the following five sub-processes: trust evaluation of anchor nodes, initial localization of unknown nodes, trust evaluation of reference nodes, selection of reference node, and secondary localization of unknown node. Simulation results demonstrate that the proposed CSLT algorithm performs better than the compared related works in terms of location security, average localization accuracy and localization ratio. PMID- 26891301 TI - Grut: A Gardening Sensor Kit for Children. AB - Food waste is one of the main problems in our society. This is mainly caused by people's behaviors and attitudes, which influence the whole food chain, from production to final consumption. In fact, food is generally perceived as a commodity by adults, who transmit this behavior to children, who in turn do not develop any consciousness about food's source. One way to reduce the problem seems to be by changing consumers' attitudes, which develop during the early years of childhood. Research has shown that after attending school garden classes, children's food-related behavior changes. Growing crops is not always easy--it can't be done in the domestic space, and this lead to a loss of the long term positive effects. This paper presents a project that tries to teach children how to grow their own food indoors and outdoors, mixing real and virtual reality, connecting something natural like a plant to the Internet of Things (or IOT, a network of physical objects virtually connected to each other and to the web). The use of sensors related to an app makes this process more fun and useful for educational purposes. The aim of the project is to change children's attitude towards food, increasing their knowledge about production and consumption, in order to reduce waste on a long term basis. The research has been developed in collaboration with Cisco NL and MediaLAB Amsterdam. The user testing has been executed with Dutch children in Amsterdam. PMID- 26891302 TI - Suppression of Strong Background Interference on E-Nose Sensors in an Open Country Environment. AB - The feature extraction technique for an electronic nose (e-nose) applied in tobacco smell detection in an open country/outdoor environment with periodic background strong interference is studied in this paper. Principal component analysis (PCA), Independent component analysis (ICA), re-filtering and a priori knowledge are combined to separate and suppress background interference on the e nose. By the coefficient of multiple correlation (CMC), it can be verified that a better separation of environmental temperature, humidity, and atmospheric pressure variation related background interference factors can be obtained with ICA. By re-filtering according to the on-site interference characteristics a composite smell curve was obtained which is more related to true smell information based on the tobacco curer's experience. PMID- 26891304 TI - Data Mining and NIR Spectroscopy in Viticulture: Applications for Plant Phenotyping under Field Conditions. AB - Plant phenotyping is a very important topic in agriculture. In this context, data mining strategies may be applied to agricultural data retrieved with new non invasive devices, with the aim of yielding useful, reliable and objective information. This work presents some applications of machine learning algorithms along with in-field acquired NIR spectral data for plant phenotyping in viticulture, specifically for grapevine variety discrimination and assessment of plant water status. Support vector machine (SVM), rotation forests and M5 trees models were built using NIR spectra acquired in the field directly on the adaxial side of grapevine leaves, with a non-invasive portable spectrophotometer working in the spectral range between 1600 and 2400 nm. The nu-SVM algorithm was used for the training of a model for varietal classification. The classifiers' performance for the 10 varieties reached, for cross- and external validations, the 88.7% and 92.5% marks, respectively. For water stress assessment, the models developed using the absorbance spectra of six varieties yielded the same determination coefficient for both cross- and external validations (R2 = 0.84; RMSEs of 0.164 and 0.165 MPa, respectively). Furthermore, a variety-specific model trained only with samples of Tempranillo from two different vintages yielded R2 = 0.76 and RMSE of 0.16 MPa for cross-validation and R2 = 0.79, RMSE of 0.17 MPa for external validation. These results show the power of the combined use of data mining and non-invasive NIR sensing for in-field grapevine phenotyping and their usefulness for the wine industry and precision viticulture implementations. PMID- 26891305 TI - Detection and Inspection of Steel Bars in Reinforced Concrete Structures Using Active Infrared Thermography with Microwave Excitation and Eddy Current Sensors. AB - The purpose of this paper is to present a multi-sensor approach to the detection and inspection of steel bars in reinforced concrete structures. In connection with our past experience related to non-destructive testing of different materials, we propose using two potentially effective methods: active infrared thermography with microwave excitation and the eddy current technique. In this article active infrared thermography with microwave excitation is analyzed both by numerical modeling and experiments. This method, based on thermal imaging, due to its characteriatics should be considered as a preliminary method for the assessment of relatively shallowly located steel bar reinforcements. The eddy current technique, on the other hand, allows for more detailed evaluation and detection of deeply located rebars. In this paper a series of measurement results, together with the initial identification of certain features of steel reinforcement bars will be presented. PMID- 26891303 TI - Development of Microfluidic Systems Enabling High-Throughput Single-Cell Protein Characterization. AB - This article reviews recent developments in microfluidic systems enabling high throughput characterization of single-cell proteins. Four key perspectives of microfluidic platforms are included in this review: (1) microfluidic fluorescent flow cytometry; (2) droplet based microfluidic flow cytometry; (3) large-array micro wells (microengraving); and (4) large-array micro chambers (barcode microchips). We examine the advantages and limitations of each technique and discuss future research opportunities by focusing on three key performance parameters (absolute quantification, sensitivity, and throughput). PMID- 26891306 TI - Development of a Rapid Throughput Assay for Identification of hNav1.7 Antagonist Using Unique Efficacious Sodium Channel Agonist, Antillatoxin. AB - Voltage-gated sodium channels (VGSCs) are responsible for the generation of the action potential. Among nine classified VGSC subtypes (Nav1.1-Nav1.9), Nav1.7 is primarily expressed in the sensory neurons, contributing to the nociception transmission. Therefore Nav1.7 becomes a promising target for analgesic drug development. In this study, we compared the influence of an array of VGSC agonists including veratridine, BmK NT1, brevetoxin-2, deltamethrin and antillatoxin (ATX) on membrane depolarization which was detected by Fluorescence Imaging Plate Reader (FLIPR) membrane potential (FMP) blue dye. In HEK-293 cells heterologously expressing hNav1.7 alpha-subunit, ATX produced a robust membrane depolarization with an EC50 value of 7.8 +/- 2.9 nM whereas veratridine, BmK NT1, and deltamethrin produced marginal response. Brevetoxin-2 was without effect on membrane potential change. The ATX response was completely inhibited by tetrodotoxin suggesting that the ATX response was solely derived from hNav1.7 activation, which was consistent with the results where ATX produced a negligible response in null HEK-293 cells. Six VGSC antagonists including lidocaine, lamotrigine, phenytoin, carbamazepine, riluzole, and 2-amino-6 trifluoromethylthiobenzothiazole all concentration-dependently inhibited ATX response with IC50 values comparable to that reported from patch-clamp experiments. Considered together, we demonstrate that ATX is a unique efficacious hNav1.7 activator which offers a useful probe to develop a rapid throughput screening assay to identify hNav1.7 antagonists. PMID- 26891307 TI - Effect of Climate Factors on the Childhood Pneumonia in Papua New Guinea: A Time Series Analysis. AB - This study aimed to assess the association between climate factors and the incidence of childhood pneumonia in Papua New Guinea quantitatively and to evaluate the variability of the effect size according to their geographic properties. The pneumonia incidence in children under five-year and meteorological factors were obtained from six areas, including monthly rainfall and the monthly average daily maximum temperatures during the period from 1997 to 2006 from national health surveillance data. A generalized linear model was applied to measure the effect size of local and regional climate factor. The pooled risk of pneumonia in children per every 10 mm increase of rainfall was 0.24% (95% confidence interval: -0.01%-0.50%), and risk per every 1 degrees C increase of the monthly mean of the maximum daily temperatures was 4.88% (95% CI: 1.57-8.30). Southern oscillation index and dipole mode index showed an overall negative effect on childhood pneumonia incidence, -0.57% and -4.30%, respectively, and the risk of pneumonia was higher in the dry season than in the rainy season (pooled effect: 12.08%). There was a variability in the relationship between climate factors and pneumonia which is assumed to reflect distribution of the determinants of and vulnerability to pneumonia in the community. PMID- 26891309 TI - Pathogens in Ornamental Waters: A Pilot Study. AB - In parks, ornamental waters of easy access and populated with animals are quite attractive to children and yet might hide threats to human health. The present work focuses on the microbiota of the ornamental waters of a Lisboa park, characterized during 2015. The results show a dynamic microbiota integrating human pathogens such as Klebsiella pneumoniae, Aeromonas spp. and Enterobacter spp., and also antibiotic resistant bacteria. K. pneumoniae and Aeromonas spp. were present as planktonic and biofilm organized bacteria. In vitro K. pneumoniae and Aeromonas spp. showed an enhanced ability to assemble biofilm at 25 degrees C than at 37 degrees C. Bacteria recovered from biofilm samples showed an increased antibiotic resistance compared to the respective planktonic counterparts. PMID- 26891308 TI - Exposure to PM2.5 and Blood Lead Level in Two Populations in Ulaanbaatar, Mongolia. AB - Approximately 60% of the households in Ulaanbaatar live in gers (a traditional Mongolian dwelling) in districts outside the legal limits of the city, without access to basic infrastructure, such as water, sewage systems, central heating, and paved roads, in contrast to apartment residents. This stark difference in living conditions creates different public health challenges for Ulaanbaatar residents. Through this research study we aim to test our hypothesis that women living in gers burning coal in traditional stoves for cooking and heating during the winter are exposed to higher concentrations of airborne PM2.5 than women living in apartments in Ulaanbaatar, Mongolia, and this exposure may include exposures to lead in coal with effects on blood lead levels. This cross-sectional study recruited a total of 50 women, 40-60 years of age, from these two settings. Air sampling was carried out during peak cooking and heating times, 5:00 p.m. 11:00 p.m., using a direct-reading instrument (TSI SidePakTM) and integrated polytetrafluoroethylene (PTFE) filters using the SKC Personal Environmental Monitor. Blood lead level (BLL) was measured using a LeadCare II rapid field test method. In our study population, measured PM2.5 geometric mean (GM) concentrations using the SidePakTM in the apartment group was 31.5 (95% CI:17-99) MUg/m3, and 100 (95% CI: 67-187) MUg/m3 in ger households (p < 0.001). The GM integrated gravimetric PM2.5 concentrations in the apartment group were 52.8 (95% CI: 39-297) MUg/m3 and 127.8 (95% CI: 86-190) MUg/m3 in ger households (p = 0.004). The correlation coefficient for the SidePakTM PM2.5 concentrations and filter based PM2.5 concentrations was r = 0.72 (p < 0.001). Blood Lead Levels were not statistically significant different between apartment residents and ger residents (p = 0.15). The BLL is statistically significant different (p = 0.01) when stratified by length of exposures outside of the home. This statistically significant difference in increased BLL could be due to occupational or frequent exposure to other sources of indoor or outdoor air pollution that were not measured. Blood lead levels from our study population are the first study measurements published on women aged 40-60 years of age in Mongolia. PMID- 26891310 TI - A Review of Groundwater Arsenic Contamination in Bangladesh: The Millennium Development Goal Era and Beyond. AB - Arsenic contamination in drinking water has a detrimental impact on human health which profoundly impairs the quality of life. Despite recognition of the adverse health implications of arsenic toxicity, there have been few studies to date to suggest measures that could be taken to overcome arsenic contamination. After the statement in 2000 WHO Bulletin that Bangladesh has been experiencing the largest mass poisoning of population in history, we researched existing literature to assess the magnitude of groundwater arsenic contamination in Bangladesh. The literature reviewed related research that had been initiated and/or completed since the implementation of the Millennium Development Goals (MDGs) under four domains: (1) extent of arsenic contamination; (2) health consequences; (3) mitigation and technologies and (4) future directions. To this means, a review matrix was established for analysis of previous literature based on these four core domains. Our findings revealed that several high-quality research articles were produced at the beginning of the MDG period, but efforts have dwindled in recent years. Furthermore, there were only a few studies conducted that focused on developing suitable solutions for managing arsenic contamination. Although the government of Bangladesh has made its population's access to safe drinking water a priority agenda item, there are still pockets of the population that continue to suffer from arsenic toxicity due to contaminated water supplies. PMID- 26891311 TI - Chronic Stress and Suicidal Thinking Among Medical Students. AB - INTRODUCTION: The subject of chronic stress and ways of dealing with it are very broad. The aim of this study was to analyze stress and anxiety and their influence on suicidal thinking among medical students. MATERIALS AND METHODS: The study was conducted in the years 2014 to 2015 in Poland, at the Medical University-Nicolaus Copernicus University, Collegium Medicum. The objective of this study was to assess chronic stress and suicidal thinking among students and how students cope with this huge problem. Descriptive statistics and chi-square analyses were conducted to detect differences. RESULTS: Analyses showed that students' life is full of stressors. Students toward the end of their education cope better with stress than students starting their university studies. Chronic stress has a strong impact on mental health and suicidal thinking among students. CONCLUSIONS: The results of the study confirmed that chronic stress and anxiety have a negative influence on mental health and also confirm a relation to suicidal thinking in medical students. Students cope with stress by listening to music, talking to relatives or people close to them, resting or engaging in sports, with cycling, running and swimming being the most common methods used to affect suicidal thinking. PMID- 26891313 TI - What Effect Does International Migration Have on the Nutritional Status and Child Care Practices of Children Left Behind? AB - Despite an increasing trend in labour migration and economic dependence on foreign migrant workers in Sri Lanka, very little is known about the child care and nutritional status of "children left behind". The aim of this study was to examine the factors influencing the nutritional status and care practices of children left behind. A sample of 321 children, 6-59 months old of international migrant workers from a cross-sectional nationally represented study were included. Care practices were assessed using ten caregiving behaviours on personal hygiene, feeding, and use of health services. Results revealed the prevalence of stunting, wasting and underweight to be 11.6, 18.2 and 24.0 percent, respectively. Father being a migrant worker has a positive effect on childcare practices and birthweight of the child. This study indicates that undernutrition remains a major concern, particularly in the poorest households where the mother is a migrant worker, also each additional 100 g increase in the birthweight of a child in a migrant household, decreases the probability of being wasted, stunted and underweight by 6%, 8% and 23% respectively. In depth study is needed to understand how labour migration affects household level outcomes related to child nutrition and childcare in order to build skills and capacities of migrant families. PMID- 26891312 TI - Leisure Time Physical Inactivity and Sedentary Behaviour and Lifestyle Correlates among Students Aged 13-15 in the Association of Southeast Asian Nations (ASEAN) Member States, 2007-2013. AB - The aim of this study was to examine the relationship between self-reported leisure time physical inactivity frequency and sedentary behaviour and lifestyle correlates among school children in the Association of Southeast Asian Nations (ASEAN) region. The analysis included 30,284 school children aged 13-15 years from seven ASEAN countries that participated in the Global School-based Student Health Survey (GSHS) between 2007 and 2013. The measure asked about overall physical activity, walking or biking to school, and on time spent sitting. Overall, the prevalence of physical inactivity was 80.4%, ranging from 74.8% in Myanmar to 90.7% in Cambodia and sedentary behaviour 33.0%, ranging from 10.5% in Cambodia and Myanmar to 42.7% in Malaysia. In multivariate logistic regression, not walking or biking to school, not attending physical education classes, inadequate vegetable consumption and lack of protective factors (peer and parental or guardian support) were associated with physical inactivity, and older age (14 and 15 years old), coming from an upper middle income country, being overweight or obese, attending physical education classes, alcohol use, loneliness, peer support and lack of parental or guardian supervision were associated with sedentary behaviour. In boys, lower socioeconomic status (in the form of having experienced hunger) and coming from a low income or lower middle income country were additionally associated with physical inactivity, and in girls, higher socioeconomic status, not walking or biking to school and being bullied were additionally associated with sedentary behaviour. In conclusion, a very high prevalence of leisure physical inactivity and sedentary behaviour among school going adolescents in ASEAN was found and several factors identified that may inform physical activity promotion programmes in school-going adolescents in ASEAN. PMID- 26891314 TI - Bioremediation of Crude Oil Contaminated Desert Soil: Effect of Biostimulation, Bioaugmentation and Bioavailability in Biopile Treatment Systems. AB - This work was aimed at evaluating the relative merits of bioaugmentation, biostimulation and surfactant-enhanced bioavailability of a desert soil contaminated by crude oil through biopile treatment. The results show that the desert soil required bioaugmentation and biostimulation for bioremediation of crude oil. The bioaugmented biopile system led to a total petroleum hydrocarbon (TPH) reduction of 77% over 156 days while the system with polyoxyethylene (20) sorbitan monooleate (Tween 80) gave a 56% decrease in TPH. The biostimulated system with indigenous micro-organisms gave 23% reduction in TPH. The control system gave 4% TPH reduction. The addition of Tween 80 led to a respiration rate that peaked in 48 days compared to 88 days for the bioaugmented system and respiration declined rapidly due to nitrogen depletion. The residual hydrocarbon in the biopile systems studied contained polyaromatics (PAH) in quantities that may be considered as hazardous. Nitrogen was found to be a limiting nutrient in desert soil bioremediation. PMID- 26891315 TI - Association between Polymorphisms and Haplotype in the ABCA1 Gene and Overweight/Obesity Patients in the Uyghur Population of China. AB - OBJECTIVE: This study aimed to detect the association between polymorphisms and haplotype in the ATP-binding cassette transporter A1 (ABCA1) gene and overweight/obese Uyghur patients in China. METHODS: A total of 259 overweight/obese patients and 276 normal weight subjects, which were randomly selected from among 3049 adult Uyghurs, were matched for age. We genotyped ABCA1 single nucleotide polymorphisms of rs2515602, rs3890182, rs2275542, rs2230806, rs1800976, and rs4149313. RESULTS: (1) The genotypic and allelic frequencies of rs2515602 and rs4149313 differed between the control group and case group. The genotypic frequency of rs2275542 also differed between the control group and case group (p < 0.05); (2) rs2515602, rs2230806, and rs4149313 polymorphisms were significantly related to risk of overweight/obese; (3) a significant linkage disequilibrium (LD) was observed between the ABCA1 gene rs2275542 with rs3890182 and rs2515602 with rs4149313. (4) the C-C-C-A-G-G, T-C-G-A-G-G, and T-T-G-G-G-A haplotypes were significant in normal weight and overweight/obese subjects (p < 0.05); (5) the levels of HDL-C (rs2515602, rs2275542, rs4149313) in normal weight subjects were different among the genotypes (p < 0.05); the levels of TC, LDL-C and TG (rs1800976) in overweight/obese subjects were different among the genotypes (p < 0.05). CONCLUSIONS: The rs2515602, rs4149313, and rs2275542 polymorphisms were associated with overweight/obese conditions among Uyghurs. Strong LD was noted between rs2275542 with rs3890182 and rs2515602 with rs4149313. The C-C-C-A-G-G and T-C-G-A-G-G haplotypes may serve as risk factors of overweight/obesity among Uyghurs. The T-T-G-G-G-A haplotype may serve as a protective factor of overweight/obesity among Uyghurs. Rs2515602, rs2275542, rs4149313, and rs1800976 polymorphisms in the ABCA1 gene may influence lipid profiles. PMID- 26891316 TI - NF45 and NF90 Bind HIV-1 RNA and Modulate HIV Gene Expression. AB - A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 and NF90 diminished the enhancement of HIV infection and gene expression. Both proteins were found to interact with the HIV RNA. RNA decay assays demonstrated that NF90, but not NF45, increased the half-life of the HIV RNA. Overall, these studies indicate that both NF45 and NF90 potentiate HIV infection through their RNA binding domains. PMID- 26891317 TI - Profile of Free Fatty Acids and Fractions of Phospholipids, Cholesterol Esters and Triglycerides in Serum of Obese Youth with and without Metabolic Syndrome. AB - The study evaluated the profile of circulating fatty acids (FA) in obese youth with and without metabolic syndrome (MetS) to determine its association with nutritional status, lifestyle and metabolic variables. A cross-sectional study was conducted in 96 young people, divided into three groups: obese with MetS (OBMS), obese (OB) and appropriate weight (AW). FA profiles were quantified by gas chromatography; waist circumference (WC), fat folds, lipid profile, high sensitivity C-reactive protein, glucose, insulin, the homeostasis model assessment (HOMA index), food intake and physical activity (PA) were assessed. The OBMS group had significantly greater total free fatty acids (FFAs), palmitic 16:0 in triglyceride (TG), palmitoleic-16:1n-7 in TG and phospholipid (PL); in the OB group, these FAs were higher than in the AW group. Dihomo-gamma-linolenic (DHGL-20:3n-6) was higher in the OBMS than the AW in PL and FFAs. Linoleic-18:2n 6 in TG and PL had the lowest proportion in the OBMS group. WC, PA, total FFA, linoleic-18:2n-6 in TG and DHGL-20:3n-6 in FFAs explained 62% of the HOMA value. The OB group presented some higher proportions of FA and biochemical values than the AW group. The OBMS had proportions of some FA in the TG, PL and FFA fractions that correlated with disturbances of MetS. PMID- 26891318 TI - Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition. AB - Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH). In the early stages, all branched-chain amino acids (BCAA) are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD) consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance. PMID- 26891319 TI - Micronutrient Fortified Condiments and Noodles to Reduce Anemia in Children and Adults--A Literature Review and Meta-Analysis. AB - Micronutrient deficiencies impose a considerable burden of disease on many middle and low income countries. Several strategies have been shown to be effective in improving micronutrient deficiencies. However, the impact of fortified condiments as well as fortified noodles is less well documented. We aimed to investigate existing evidence on the impact of micronutrient fortified condiments and noodles on hemoglobin, anemia, and functional outcomes in children and adults (age: 5 to 50 years). We conducted a literature review in electronic databases. In addition, we screened the homepages of relevant organizations and journals. We included randomized controlled trials (RCT). Of 1046 retrieved studies, 14 RCT provided data for the meta-analysis. Micronutrient fortification of condiments and noodles increased hemoglobin concentrations by 0.74 g/dL (95%-confidence intervals (95% CI): 0.56 to 0.93; 12 studies) and 0.3 g/dL (95%-CI: 0.12 to 0.48; 1 study), respectively. Micronutrient fortification also led to a reduced risk of having anemia (risk ratio 0.59 (95%-CI 0.44 to 0.80)). Ferritin concentrations increased with fortified condiments. Functional outcomes were rarely assessed and showed mixed results. The use of micronutrient fortified condiments can be a strategy to reduce anemia in children and adults due to micronutrient deficiencies. The effect of fortified noodles seems to be smaller. PMID- 26891320 TI - Is Higher Consumption of Animal Flesh Foods Associated with Better Iron Status among Adults in Developed Countries? A Systematic Review. AB - Iron deficiency (ID) is the most prevalent nutrient deficiency within the developed world. This is of concern as ID has been shown to affect immunity, thermoregulation, work performance and cognition. Animal flesh foods provide the richest and most bioavailable source of dietary (haem) iron, however, it is unclear whether low animal flesh diets contribute to ID. This systematic review aimed to investigate whether a higher consumption of animal flesh foods is associated with better iron status in adults. CINAHL, Cochrane, EMBASE and MEDLINE were searched for published studies that included adults (>=18 years) from developed countries and measured flesh intakes in relation to iron status indices. Eight experimental and 41 observational studies met the inclusion criteria. Generally, studies varied in population and study designs and results were conflicting. Of the seven high quality studies, five showed a positive association between animal flesh intake (85-300 g/day) and iron status. However, the optimum quantity or frequency of flesh intake required to maintain or achieve a healthy iron status remains unclear. Results show a promising relationship between animal flesh intake and iron status, however, additional longitudinal and experimental studies are required to confirm this relationship and determine optimal intakes to reduce ID development. PMID- 26891323 TI - Automatic 1H-NMR Screening of Fatty Acid Composition in Edible Oils. AB - In this work, we introduce an NMR-based screening method for the fatty acid composition analysis of edible oils. We describe the evaluation and optimization needed for the automated analysis of vegetable oils by low-field NMR to obtain the fatty acid composition (FAC). To achieve this, two scripts, which automatically analyze and interpret the spectral data, were developed. The objective of this work was to drive forward the automated analysis of the FAC by NMR. Due to the fact that this protocol can be carried out at low field and that the complete process from sample preparation to printing the report only takes about 3 min, this approach is promising to become a fundamental technique for high-throughput screening. To demonstrate the applicability of this method, the fatty acid composition of extra virgin olive oils from various Spanish olive varieties (arbequina, cornicabra, hojiblanca, manzanilla, and picual) was determined by 1H-NMR spectroscopy according to this protocol. PMID- 26891324 TI - Dietary Flavonols Intake and Risk of Esophageal and Gastric Cancer: A Meta Analysis of Epidemiological Studies. AB - BACKGROUND: Esophageal cancer (EC) and gastric cancer (GC) are common cancers and leading causes of cancer deaths worldwide. Many studies have investigated the association between dietary flavonols intake and the risk of EC and GC, but the results are inconsistent. Hence, we conducted a systematic analysis of relevant population-based studies to assess the association and derive a more precise estimation. METHODS: The Cochrane, PubMed and Embase databases were searched to identify articles published through January 2016 that met the predetermined inclusion criterion. Twelve studies involving 4593 patients and 519,378 controls were included. RESULTS: The summary odds ratios (ORs) of EC, GC and the two combined were respectively 0.88 (95% CI: 0.73-1.08), 0.80 (95% CI: 0.70-0.91) and 0.83 (95% CI: 0.74-0.92) for the highest category of dietary flavonols intake compared with the lowest. No significant heterogeneities were observed in these studies. Further analysis showed that the pooled ORs of EC and GC for cohort, population-based case-control and hospital-based case-control studies were 0.90 (95% CI: 0.61-1.34), 0.92 (95% CI: 0.72-1.18), 0.68 (95% CI: 0.38-1.24) and 0.83 (95% CI: 0.65-1.06), 0.84 (95% CI: 0.45-1.59), 0.70 (95% CI: 0.56-0.88). The subgroup analyses revealed a significant association of flavonol intake with a reduced risk of noncardia gastric adenocarcinoma but not gastric cardia adenocarcinoma. Moreover, significant inverse associations of flavonol intake with GC risk were observed in women but not in men, in smokers but not in nonsmokers, in European populations but not in American populations. Similarly, a significant inverse association of flavonols intake with EC risk was also observed in smokers but not in nonsmokers. CONCLUSION: High intake of dietary flavonols is significantly related to a reduced risk of GC, especially in women and smokers. PMID- 26891322 TI - Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet. AB - Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0.02%, w/w). The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT) weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, interferon-gamma, and interleukin-6, and prevented HFD induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance. PMID- 26891325 TI - An Insight into the Triabin Protein Family of American Hematophagous Reduviids: Functional, Structural and Phylogenetic Analysis. AB - A transcriptomic analysis of the saliva of T. pallidipennis together with a short proteomic analysis were carried out to reveal novel primary structures of the lipocalin/triabin protein families in this reduviid. Although triabins share some structural characteristics to lipocalins and they are classified as in the calcyn/lipocalin superfamily, triabins differ from lipocalins in the direction of beta-strands in the general conformation of the beta-barrel. The triabin protein family encompasses a wide variety of proteins, which disrupt the hemostasis of warm-blooded animals. Likewise, the function of proteins classified as triabins includes proteins that are carriers of small molecules, protease inhibitors, binders of specific cell-surface receptors as well as proteins that form complexes with other macromolecules. For example, triabin and pallidipin from the saliva of T. pallidipennis are thrombin and platelet aggregation inhibitors, respectively; triplatin from T. infestans binds to thromboxane A2; and nitrophorin from Rhodnius prolixus carries nitric oxide. Therefore, based on 42 new transcriptome sequences of triabins from the salivary glands of T. pallidipennis reported at present, and on triabin sequences of other American hematophagous reduviids already reported in the literature, subfamilies of triabins were proposed following phylogenetic analyses and functional characterization of triabin members. Eight subfamilies of proteins were recognized with known functions, which were the nitrophorin and amine binding proteins, Rhodnius prolixus aggregation inhibitor, triafestin, triatin, dipetalodipin and pallidipin, triplatin and infestilin, dimiconin and triabin, and procalin subfamilies. Interestingly, 70% of the analyzed sequences came from these eight subfamilies because there was no biological function associated with them, implying the existence of a vast number of proteins with potential novel biological activities. PMID- 26891321 TI - Myricetin: A Dietary Molecule with Diverse Biological Activities. AB - Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson's and Alzheimer's. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound's ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities. PMID- 26891326 TI - Mycotoxin Contamination in the EU Feed Supply Chain: A Focus on Cereal Byproducts. AB - Mycotoxins represent a risk to the feed supply chain with an impact on economies and international trade. A high percentage of feed samples have been reported to be contaminated with more than one mycotoxin. In most cases, the concentrations were low enough to ensure compliance with the European Union (EU) guidance values or maximum admitted levels. However, mycotoxin co-contamination might still exert adverse effects on animals due to additive/synergistic interactions. Studies on the fate of mycotoxins during cereal processing, such as milling, production of ethanol fuels, and beer brewing, have shown that mycotoxins are concentrated into fractions that are commonly used as animal feed. Published data show a high variability in mycotoxin repartitioning, mainly due to the type of mycotoxins, the level and extent of fungal contamination, and a failure to understand the complexity of food processing technologies. Precise knowledge of mycotoxin repartitioning during technological processes is critical and may provide a sound technical basis for feed managers to conform to legislation requirements and reduce the risk of severe adverse market and trade repercussions. Regular, economical and straightforward feed testing is critical to reach a quick and accurate diagnosis of feed quality. The use of rapid methods represents a future challenge. PMID- 26891327 TI - Lolitrem B and Indole Diterpene Alkaloids Produced by Endophytic Fungi of the Genus Epichloe and Their Toxic Effects in Livestock. AB - Different group of alkaloids are produced during the symbiotic development of fungal endophytes of the genus Epichloe in grass. The structure and toxicity of the compounds vary considerably in mammalian herbivores and in crop pests. Alkaloids of the indole-diterpene group, of which lolitrem B is the most toxic, were first characterized in endophyte-infected perennial ryegrass, and are responsible for "ryegrass staggers." Ergot alkaloids, of which ergovaline is the most abundant ergopeptide alkaloid produced, are also found in ryegrass, but generally at a lower rate than lolitrem B. Other alkaloids such as lolines and peramine are toxic for crop pests but have weak toxicological properties in mammals. The purpose of this review is to present indole-diterpene alkaloids produced in endophyte infected ryegrass from the first characterization of ryegrass staggers to the determination of the toxicokinetics of lolitrem B and of their mechanism of action in mammals, focusing on the different factors that could explain the worldwide distribution of the disease. Other indole diterpene alkaloids than lolitrem B that can be found in Epichloe infected ryegrass, and their tremorgenic properties, are presented in the last section of this review. PMID- 26891328 TI - Functional Genomic Analysis of Aspergillus flavus Interacting with Resistant and Susceptible Peanut. AB - In the Aspergillus flavus (A. flavus)-peanut pathosystem, development and metabolism of the fungus directly influence aflatoxin contamination. To comprehensively understand the molecular mechanism of A. flavus interaction with peanut, RNA-seq was used for global transcriptome profiling of A. flavus during interaction with resistant and susceptible peanut genotypes. In total, 67.46 Gb of high-quality bases were generated for A. flavus-resistant (af_R) and susceptible peanut (af_S) at one (T1), three (T2) and seven (T3) days post inoculation. The uniquely mapped reads to A. flavus reference genome in the libraries of af_R and af_S at T2 and T3 were subjected to further analysis, with more than 72% of all obtained genes expressed in the eight libraries. Comparison of expression levels both af_R vs. af_S and T2 vs. T3 uncovered 1926 differentially expressed genes (DEGs). DEGs associated with mycelial growth, conidial development and aflatoxin biosynthesis were up-regulated in af_S compared with af_R, implying that A. flavus mycelia more easily penetrate and produce much more aflatoxin in susceptible than in resistant peanut. Our results serve as a foundation for understanding the molecular mechanisms of aflatoxin production differences between A. flavus-R and -S peanut, and offer new clues to manage aflatoxin contamination in crops. PMID- 26891330 TI - Nephrotoxicity as a Dose-Limiting Factor in a High-Dose Cisplatin-Based Chemoradiotherapy Regimen for Head and Neck Carcinomas. AB - PURPOSE: Loco-regional control and organ preservation are significantly improved with concomitant cisplatin/radiotherapy and are compromised with less than 5% grade 3 nephrotoxicity (creatinine clearance 15-29 mL/min). However, although clinically important, in none of the randomized trials is grade 2 nephrotoxicity (defined as creatinine clearance 59-30 mL/min) mentioned. In this study, we assessed nephrotoxicity in daily practice among patients treated with high-dose cisplatin (100 mg/m2 on days 1, 22, and 43), concurrently with chemoradiotherapy (CCRT) and the impact on treatment modifications. METHODS: 208 patients with advanced-stage malignancies of the head and neck region were evaluated. All patients were treated with high-dose cisplatin CCRT. The main outcome parameters were nephrotoxicity (defined as creatinine clearance grade 2 or more) and cumulative doses of cisplatin and radiation. RESULTS: 133 patients (64%) completed all pre-planned courses of cisplatin. Nephrotoxicity was the main reason to discontinue the chemotherapy. Grade 3 nephrotoxicity was seen in 16 patients (8%) while grade 2 nephrotoxicity was seen in 53 patients (25%). Thirty six patients (17%) could not complete the pre-planned chemotherapy due to nephrotoxicity. CONCLUSIONS: In head and neck cancer patients, nephrotoxicity grade 2 is under-reported but is the major factor for discontinuing cisplatin during CCRT. PMID- 26891332 TI - Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria. AB - During asymptomatic bacteriuria (ABU), bacteria colonize the urinary tract for extended periods of time without causing symptoms of urinary tract infection. Previous studies indicate that many Escherichia coli (E. coli) strains that cause ABU have evolved from uropathogenic E. coli (UPEC) by reductive evolution and loss of the ability to express functional virulence factors. For instance, the prototype ABU strain 83972 has a smaller genome than UPEC strains with deletions or point mutations in several virulence genes. To understand the mechanisms of bacterial adaptation and to find out whether the bacteria adapt in a host specific manner, we compared the complete genome sequences of consecutive reisolates of ABU strain 83972 from different inoculated individuals and compared them with the genome of the parent strain. Reisolates from different hosts exhibited individual patterns of genomic alterations. Non-synonymous SNPs predominantly occurred in coding regions and often affected the amino acid sequence of proteins with global or pleiotropic regulatory function. These gene products are involved in different bacterial stress protection strategies, and metabolic and signaling pathways. Our data indicate that adaptation of E. coli 83972 to prolonged growth in the urinary tract involves responses to specific growth conditions and stresses present in the individual hosts. Accordingly, modulation of gene expression required for survival and growth under stress conditions seems to be most critical for long-term growth of E. coli 83972 in the urinary tract. PMID- 26891331 TI - Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism in Modulating Cancer Risk in Asian Population. AB - Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p <= 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p <= 0.0001; AA vs. GG + GA; OR = 1.52, p <= 0.004, A vs. G allele: OR = 1.41, p <= 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p <= 0.0001; CT + TT vs. CC: OR = 1.24, p <= 0.0001; TT vs. CC + CT; OR = 1.17, p <= 0.005, T vs. C allele: OR = 1.16, p <= 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk. PMID- 26891333 TI - Improving the Understanding of Psychological Factors Contributing to Horse Related Accident and Injury: Context, Loss of Focus, Cognitive Errors and Rigidity. AB - While the role of the horse in riding hazards is well recognised, little attention has been paid to the role of specific theoretical psychological processes of humans in contributing to and mitigating risk. The injury, mortality or compensation claim rates for participants in the horse-racing industry, veterinary medicine and equestrian disciplines provide compelling evidence for improving risk mitigation models. There is a paucity of theoretical principles regarding the risk of injury and mortality associated with human-horse interactions. In this paper we introduce and apply the four psychological principles of context, loss of focus, global cognitive style and the application of self as the frame of reference as a potential approach for assessing and managing human-horse risks. When these principles produce errors that are combined with a rigid self-referenced point, it becomes clear how rapidly risk emerges and how other people and animals may repeatedly become at risk over time. Here, with a focus on the thoroughbred racing industry, veterinary practice and equestrian disciplines, we review the merits of contextually applied strategies, an evolving reappraisal of risk, flexibility, and focused specifics of situations that may serve to modify human behaviour and mitigate risk. PMID- 26891334 TI - Look Before You Leap: What Are the Obstacles to Risk Calculation in the Equestrian Sport of Eventing? AB - All horse-riding is risky. In competitive horse sports, eventing is considered the riskiest, and is often characterised as very dangerous. But based on what data? There has been considerable research on the risks and unwanted outcomes of horse-riding in general, and on particular subsets of horse-riding such as eventing. However, there can be problems in accessing accurate, comprehensive and comparable data on such outcomes, and in using different calculation methods which cannot compare like with like. This paper critically examines a number of risk calculation methods used in estimating risk for riders in eventing, including one method which calculates risk based on hours spent in the activity and in one case concludes that eventing is more dangerous than motorcycle racing. This paper argues that the primary locus of risk for both riders and horses is the jump itself, and the action of the horse jumping. The paper proposes that risk calculation in eventing should therefore concentrate primarily on this locus, and suggests that eventing is unlikely to be more dangerous than motorcycle racing. The paper proposes avenues for further research to reduce the likelihood and consequences of rider and horse falls at jumps. PMID- 26891329 TI - Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors. AB - The sonic hedgehog (Shh) signaling pathway is a major regulator of cell differentiation, cell proliferation, and tissue polarity. Aberrant activation of the Shh pathway has been shown in a variety of human cancers, including, basal cell carcinoma, malignant gliomas, medulloblastoma, leukemias, and cancers of the breast, lung, pancreas, and prostate. Tumorigenesis, tumor progression and therapeutic response have all been shown to be impacted by the Shh signaling pathway. Downstream effectors of the Shh pathway include smoothened (SMO) and glioma-associated oncogene homolog (GLI) family of zinc finger transcription factors. Both are regarded as important targets for cancer therapeutics. While most efforts have been devoted towards pharmacologically targeting SMO, developing GLI-targeted approach has its merit because of the fact that GLI proteins can be activated by both Shh ligand-dependent and -independent mechanisms. To date, two SMO inhibitors (LDE225/Sonidegib and GDC 0449/Vismodegib) have received FDA approval for treating basal cell carcinoma while many clinical trials are being conducted to evaluate the efficacy of this exciting class of targeted therapy in a variety of cancers. In this review, we provide an overview of the biology of the Shh pathway and then detail the current landscape of the Shh-SMO-GLI pathway inhibitors including those in preclinical studies and clinical trials. PMID- 26891335 TI - Cancer Risk and Eicosanoid Production: Interaction between the Protective Effect of Long Chain Omega-3 Polyunsaturated Fatty Acid Intake and Genotype. AB - Dietary inclusion of fish and fish supplements as a means to improve cancer prognosis and prevent tumour growth is largely controversial. Long chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA), eicosapentaenoic acid and docosahexaenoic acid, may modulate the production of inflammatory eicosanoids, thereby influencing local inflammatory status, which is important in cancer development. Although in vitro studies have demonstrated inhibition of tumour cell growth and proliferation by LCn-3 PUFA, results from human studies have been mainly inconsistent. Genes involved in the desaturation of fatty acids, as well as the genes encoding enzymes responsible for eicosanoid production, are known to be implicated in tumour development. This review discusses the current evidence for an interaction between genetic polymorphisms and dietary LCn-3 PUFA in the risk for breast, prostate and colorectal cancers, in regards to inflammation and eicosanoid synthesis. PMID- 26891336 TI - Melatonin and Sleep-Wake Rhythms before and after Ocular Lens Replacement in Elderly Humans. AB - Light of short wavelengths has been shown to play a key role in non-image forming responses. Due to aging, the ocular lens becomes more yellow reducing the transmission of short wavelengths in the elderly. In the present study, we make use of cataract surgery to investigate the effects of a relative increase of short wavelength transmission on melatonin- and sleep-wake rhythms (N = 14). We observed, on average, a delay of the sleep-wake and the nocturnal melatonin rhythms after cataract surgery. This delay is tentatively attributed to a relatively large increase of light transmittance in the evening hours more than an increase of the already relatively high light intensities found in the daytime. The later phase that we observed after cataract surgery (clear lens) as compared to the earlier phase observed before cataract (yellowish lens) is in agreement with the general later phase reported in the young (clear lens) population. PMID- 26891338 TI - Subjective well-being: gender differences in Holocaust survivors-specific and cross-national effects. AB - OBJECTIVES: Subjective well-being (SWB) has become an important concept in evaluating older adults' quality of life. The cognitive and emotional evaluations which are used to appraise it differ in structure, characteristics, and effects on life. The purpose of this study was to support hypotheses regarding expected Holocaust survivors-specific effects and cross-cultural differences on three indicators of SWB. METHOD: We recruited samples of 50 male and female Israeli Holocaust survivors, other older Israelis, and older Canadians (N = 300) for allowing us to distinguish survivors-specific effects from cross-national differences. State anxiety, depressive symptoms, and life-satisfaction were compared across groups of men and women. Where univariate differences were detected, post hoc comparisons were computed to determine which of the groups significantly differed. RESULTS: In general, a higher level of SWB was found among Canadians in comparison to both comparative Israeli groups. Level of depressive symptoms was significantly higher among women survivors than in the other two groups. Both groups of Israeli women had higher scores on anxiety than Canadian Women; less apparent were differences across groups of men. Life satisfaction did not differ among the groups. CONCLUSIONS: Our findings regarding depression support the survivor-specific effect hypothesis for women, and a national effect on anxiety, but not any effect on life-satisfaction. These findings suggest significant differences in impacts of traumatic life events on cognitive versus emotional indicators of SWB. This issue should be further investigated due to its practical implications in use of various measures of SWB with people who experienced traumatic events. PMID- 26891337 TI - The Time Is Right to Focus on Model Organism Metabolomes. AB - Model organisms are an essential component of biological and biomedical research that can be used to study specific biological processes. These organisms are in part selected for facile experimental study. However, just as importantly, intensive study of a small number of model organisms yields important synergies as discoveries in one area of science for a given organism shed light on biological processes in other areas, even for other organisms. Furthermore, the extensive knowledge bases compiled for each model organism enable systems-level understandings of these species, which enhance the overall biological and biomedical knowledge for all organisms, including humans. Building upon extensive genomics research, we argue that the time is now right to focus intensively on model organism metabolomes. We propose a grand challenge for metabolomics studies of model organisms: to identify and map all metabolites onto metabolic pathways, to develop quantitative metabolic models for model organisms, and to relate organism metabolic pathways within the context of evolutionary metabolomics, i.e., phylometabolomics. These efforts should focus on a series of established model organisms in microbial, animal and plant research. PMID- 26891339 TI - Integrated approach to health screening of former department of energy workers detects both occupational and non-occupational illness. AB - BACKGROUND: The National Supplemental Screening Program (NSSP) uses a Total Worker Health(TM) approach to address U.S. Department of Energy (DOE) former worker health. This article provides the design of the integrated occupational health screening and promotion program. METHODS: The NSSP implemented a web-based relational health records system to process demographic, exposure, and clinical data. We present medical findings for 12,000 DOE former workers that completed an initial NSSP medical screening between October 1, 2005 and October 4, 2013. We discuss the DOE former worker participant population and the exposure-based and non-occupational medical screening tests used. RESULTS: The NSSP identified potential occupationally related health conditions in 40.5% of those screened. Notably, we identified 85.8% of participants with addressable non-occupational health conditions, many of which were previously undiagnosed. CONCLUSION: The NSSP demonstrates that the identification of potential occupational health issues in conjunction with addressable non-occupational health conditions provides former workers with information to more effectively manage health. PMID- 26891340 TI - Misuse of booster cushions among children and adults in Shanghai-an observational and attitude study during buckling up. AB - OBJECTIVE: Traffic crashes are one of the leading causes of fatalities among Chinese children. Booster cushion usage in China is low, and there are no studies showing how a population with limited experience handles booster cushions during buckling up. The purpose of this study was to evaluate the handling of and explore the attitudes toward booster cushions among children, parents, and grandparents in Shanghai. METHODS: An observational study including a convenience sample of 254 children aged 4-12 years was conducted in 2 passenger cars at a shopping center in Shanghai. Parents, grandparents, or the children themselves buckled up the child on 2 types of booster cushions, a 2-stage integrated booster cushion (IBC) and an aftermarket booster cushion (BC). The test participants were observed during buckling up, first without and then with instructions. The test leaders conducted structured interviews. RESULTS: Ninety-eight percent of the uninstructed participants failed to buckle up without identified misuse on the aftermarket booster cushion and 31% of those uninstructed on the integrated booster cushion. The majority of misuse was severe, including placing the belt behind the arm and the lap belt routing above the guiding loops. Instruction reduced misuse to 58% (BC) and 12% (IBC), respectively, and, in particular, severe misuse. Some misuse was related to limited knowledge of how to buckle up on the booster cushion, and some misuse was intentional in order to reduce discomfort. The participants, both children and adults, reported that they preferred the IBC due to good comfort and convenience. Safety was reported as the main reason for adults using booster cushions in general, whereas children reported comfort as the most important motivation. CONCLUSIONS: Education is needed to ensure frequent and correct use of booster cushions in China and to raise safety awareness among children and adults. Furthermore, it is important that the booster cushions offer intuitively correct usage to a population with limited experience of booster cushions. This is the first study published on the handling of and attitude toward booster cushions after child restraints laws were introduced in Shanghai 2014. PMID- 26891341 TI - Traumatic luxation of the globe: A 6-year follow-up. AB - A 25-year-old man was involved in a motor vehicle accident. The left globe was luxated out of orbit with total optic nerve avulsion. The globe was intact without any penetration and put back into the orbit. Although the patient has no light perception, he is grateful for satisfactory cosmetic results with 6-year follow-up. PMID- 26891342 TI - Bayesian assurance and sample size determination in the process validation life cycle. AB - Validation of pharmaceutical manufacturing processes is a regulatory requirement and plays a key role in the assurance of drug quality, safety, and efficacy. The FDA guidance on process validation recommends a life-cycle approach which involves process design, qualification, and verification. The European Medicines Agency makes similar recommendations. The main purpose of process validation is to establish scientific evidence that a process is capable of consistently delivering a quality product. A major challenge faced by manufacturers is the determination of the number of batches to be used for the qualification stage. In this article, we present a Bayesian assurance and sample size determination approach where prior process knowledge and data are used to determine the number of batches. An example is presented in which potency uniformity data is evaluated using a process capability metric. By using the posterior predictive distribution, we simulate qualification data and make a decision on the number of batches required for a desired level of assurance. PMID- 26891343 TI - Diesel exhaust exposures in port workers. AB - Exposure to diesel engine exhaust has been linked to increased cancer risk and cardiopulmonary diseases. Diesel exhaust is a complex mixture of chemical substances, including a particulate fraction mainly composed of ultrafine particles, resulting from the incomplete combustion of fuel. Diesel trucks are known to be an important source of diesel-related air pollution, and areas with heavy truck traffic are associated with higher air pollution levels and increased public health problems. Several indicators have been proposed as surrogates for estimating exposures to diesel exhaust but very few studies have focused specifically on monitoring the ultrafine fraction through the measurement of particle number concentrations. The aim of this study is to assess occupational exposures of gate controllers at the port of Montreal, Canada, to diesel engine emissions from container trucks by measuring several surrogates through a multimetric approach which includes the assessment of both mass and number concentrations and the use of direct reading devices. A 10-day measurement campaign was carried out at two terminal checkpoints at the port of Montreal. Respirable elemental and organic carbon, PM1, PM2.5, PMresp (PM4), PM10, PMtot (inhalable fraction), particle number concentrations, particle size distributions, and gas concentrations (NO2, NO, CO) were monitored. Gate controllers were exposed to concentrations of contaminants associated with diesel engine exhaust (elemental carbon GM = 1.6 ug/m(3); GSD = 1.6) well below recommended occupational exposure limits. Average daily particle number concentrations ranged from 16,544-67,314 particles/cm3 (GM = 32,710 particles/cm3; GSD = 1.6). Significant Pearson correlation coefficients were found between daily elemental carbon, PM fractions and particle number concentrations, as well as between total carbon, PM fractions and particle number concentrations. Significant correlation coefficients were found between particle number concentrations and the number of trucks and wind speed (R(2) = 0.432; p < 0.01). The presence of trucks with cooling systems and older trucks with older exhaust systems was associated with peak concentrations on the direct reading instruments. The results highlight the relevance of direct reading instruments in helping to identify sources of exposure and suggest that monitoring particle number concentrations improves understanding of workers' exposures to diesel exhaust. This study, by quantifying workers' exposure levels through a multimetric approach, contributes to the further understanding of occupational exposures to diesel engine exhaust. PMID- 26891346 TI - Does cerebral hypoxia facilitate central fatigue? AB - NEW FINDINGS: What is the topic of this review? This review addresses whether a mismatch between cerebral O2 demand and delivery accelerates the development of central fatigue during endurance-type exercise. What advances does it highlight? The difficulty with studying the importance of cerebral O2 availability for exercise performance is to manipulate cerebral O2 availability independently of muscular O2 availability. The different approaches to overcome this limitation indicate that cerebral oxygenation is not a major limiting factor in normoxia, but may limit performance in submaximal exercise tasks in hypoxia. Central fatigue originates within the central nervous system and is characterized by a decrease in voluntary muscle activation. Reduced systemic O2 availability can facilitate central fatigue by enhancing the afferent input of the chemosensitive nerves that play a pivotal role in development of central fatigue. There is accumulating evidence that, in some situations, inadequate O2 availability to the brain itself promotes central fatigue. This short review presents some of the recent findings supporting a direct effect of inadequate cerebral O2 availability on central fatigue and addresses the persisting limitations. PMID- 26891347 TI - An Universal and Easy-to-Use Model for the Pressure of Arbitrary-Shape 3D Multifunctional Integumentary Cardiac Membranes. AB - Recently developed concepts for 3D, organ-mounted electronics for cardiac applications require a universal and easy-to-use mechanical model to calculate the average pressure associated with operation of the device, which is crucial for evaluation of design efficacy and optimization. This work proposes a simple, accurate, easy-to-use, and universal model to quantify the average pressure for arbitrary-shape organs. PMID- 26891345 TI - Interactive Relationships Between Sex-Related Alcohol Expectancies and Delay Discounting on Risky Sex. AB - BACKGROUND: Sex-related alcohol expectancies reflect the degree to which a person believes alcohol will affect her or his sexual behavior. Sex-related alcohol expectancies have been found to be predictors of drinking in sexual situations and engagement in risky sexual behavior after drinking. However, less is known about individual characteristics that may moderate these associations. Building upon recent evidence that steep delay discounting is associated with alcohol related sexual risk taking, this study aimed to test the hypothesis that the associations between sex-related alcohol expectancies and alcohol-related sexual risk taking would be stronger among individuals who discount delayed rewards more steeply. METHODS: The current sample comprised 126 Emergency Department patients (Mage = 27.37; 55% male) who reported high-risk alcohol use and sexual behavior during the past 3 months. Sex-related alcohol expectancies were assessed in 3 behavioral domains: increased riskiness, decreased nervousness, and enhanced sexuality. RESULTS: All 3 expectancy domains were associated with quantity and frequency of alcohol use, as well as percentage of alcohol-related condomless sex. Delay discounting moderated 2 of these relationships, such that the associations between expectancies for alcohol-induced sexual risk taking and the enhancement of sexuality and percentage of alcohol-related sexual risk-taking were significantly stronger in individuals who exhibited steeper delay discounting. CONCLUSIONS: These findings suggest that individuals who both discount delayed rewards more steeply and hold strong sex-related alcohol expectancies are a particularly high-risk population. Such individuals may benefit from a combination of novel preventive strategies targeting sex-related alcohol expectancies and impulsive decision making. PMID- 26891348 TI - Facile Preparation of Ni2P with a Sulfur-Containing Surface Layer by Low Temperature Reduction of Ni2P2S6. AB - Preparation of Ni2P by temperature-programmed reduction (TPR) of a phosphate precursor is challenging because the P-O bond is strong. An alternative approach to synthesizing Ni2P, by reduction of nickel hexathiodiphosphate (Ni2P2S6), is presented. Conversion of Ni2P2S6 into Ni2P occurs at 200-220 degrees C, a temperature much lower than that required by the conventional TPR method (typically 500 degrees C). A sulfur-containing layer with a thickness of about 4.7 nm, composed of tiny crystallites, was observed at the surface of the obtained Ni2 P catalyst (Ni2P-S). This is a direct observation of the sulfur containing layer of Ni2P, or the so-called nickel phosphosulfide phase. Both the hydrodesulfurization activity and the selective hydrogenation performance of Ni2P S were superior to that of the catalyst prepared by the TPR method, suggesting a positive role of sulfur on the surface of Ni2P-S. These features render Ni2P-S a legitimate alternative non-precious metal catalyst for hydrogenation reactions. PMID- 26891344 TI - Visceral Fat Accumulation, Insulin Resistance, and Elevated Depressive Symptoms in Middle-Aged Japanese Men. AB - OBJECTIVE: To investigate visceral fat accumulation and markers of insulin resistance in relation to elevated depressive symptoms (EDS). METHODS: Participants were 4,333 male employees (mean age, 49.3 years) who underwent abdominal computed tomography scanning, measured fasting insulin, and did not self-report diabetes and mental disorders under treatment and history of cancer, myocardial infarction, and stroke. Multivariable logistic regression was used to assess the association of EDS with abdominal fat deposition and markers of insulin resistance. RESULTS: Visceral fat area (VFA) and fasting insulin were significantly, positively associated with EDS. Multivariable-adjusted odds ratios (95% confidence interval) of high VFA for the lowest through highest quartile of depression score were 1 (reference), 1.18 (0.97-1.42), 1.25 (1.02-1.54), 1.23 (1.01-1.51), respectively, and corresponding figures for high fasting insulin were 1 (reference), 0.98 (0.80-1.19), 1.12 (0.91-1.38), and 1.29 (1.06-1.57), respectively. Subcutaneous fat area was not associated with EDS. CONCLUSIONS: Results suggest that EDS is related to visceral, but not subcutaneous, fat accumulation and insulin resistance in middle-aged Japanese men. PMID- 26891349 TI - Establishment of a Wolbachia Superinfection in Aedes aegypti Mosquitoes as a Potential Approach for Future Resistance Management. AB - Wolbachia pipientis is an endosymbiotic bacterium estimated to chronically infect between 40-75% of all arthropod species. Aedes aegypti, the principle mosquito vector of dengue virus (DENV), is not a natural host of Wolbachia. The transinfection of Wolbachia strains such as wAlbB, wMel and wMelPop-CLA into Ae. aegypti has been shown to significantly reduce the vector competence of this mosquito for a range of human pathogens in the laboratory. This has led to wMel transinfected Ae. aegypti currently being released in five countries to evaluate its effectiveness to control dengue disease in human populations. Here we describe the generation of a superinfected Ae. aegypti mosquito line simultaneously infected with two avirulent Wolbachia strains, wMel and wAlbB. The line carries a high overall Wolbachia density and tissue localisation of the individual strains is very similar to each respective single infected parental line. The superinfected line induces unidirectional cytoplasmic incompatibility (CI) when crossed to each single infected parental line, suggesting that the superinfection would have the capacity to replace either of the single constituent infections already present in a mosquito population. No significant differences in fitness parameters were observed between the superinfected line and the parental lines under the experimental conditions tested. Finally, the superinfected line blocks DENV replication more efficiently than the single wMel strain when challenged with blood meals from viremic dengue patients. These results suggest that the deployment of superinfections could be used to replace single infections and may represent an effective strategy to help manage potential resistance by DENV to field deployments of single infected strains. PMID- 26891351 TI - Transport of carboxymethyl cellulose-coated zerovalent iron nanoparticles in a sand tank: Effects of sand grain size, nanoparticle concentration and injection velocity. AB - The transport of nanoscale zerovalent iron (NZVI) particles colloidally stabilized with 70,000 Da carboxymethyl cellulose (CMC), through sands with mean grain diameters of 180, 340 and 1140 MUm (referred to as fine, intermediate and coarse-sized sand, respectively) was investigated in a 70-cm long, two dimensional tank. The effect of NZVI concentrations (1 and 3 g-Fe L(-1)) and CMC concentrations (1 and 2 g L(-1)) and injection velocities (0.96 and 0.40 cm min( 1)) on particle transport were also evaluated with the intermediate sand. The overall NZVI mass fractions eluted from the tank were 36%, 25% and 16% in the coarse, intermediate and fine sands, respectively, when injected with 1 g L(-1) NZVI stabilized in 1 g L(-1) CMC. However, the mass fraction eluted reduced to 2.33% when the injection velocity was reduced from 0.96 to 0.40 cm min(-1) in the intermediate-sized sand. Maximum transport efficiency (38% NZVI mass eluted) in the intermediate-sized sand was achieved with 3 g L(-1) NZVI suspended in 2 g L( 1) CMC at an injection velocity of 0.96 cm min(-1). The transport efficiency was substantially decreased (11% NZVI mass eluted) when 3 g L(-1) NZVI was stabilized with only 1 g L(-1) CMC. The NZVI mean particle diameters in the porewaters remained unchanged at different locations in the tank suggesting that straining or gravity settling did not influence NZVI deposition. After NZVI injection, the hydraulic conductivity in the tank reduced by 80%-96%, depending on the CMC concentration and injection velocity. PMID- 26891352 TI - Effects of adding bulking agent, inorganic nutrient and microbial inocula on biopile treatment for oil-field drilling waste. AB - Contamination from oil-field drilling waste is a worldwide environmental problem. This study investigated the performance of four bench-scale biopiles in treating drilling waste: 1) direct biopile (DW), 2) biopile plus oil-degrading microbial consortium (DW + M), 3) biopile plus microbial consortium and bulking agents (saw dust) (DW + M + BA), 4) biopile plus microbial consortium, bulking agents, and inorganic nutrients (Urea and K2HPO4) (DW + M + BA + N). Ninety days of biopiling removed 41.0%, 44.0%, 55.7% and 87.4% of total petroleum hydrocarbon (TPH) in the pile "DW", "DW + M", "DW + M + BA", and "DW + M + BA + N" respectively. Addition of inorganic nutrient and bulking agents resulted in a 56.9% and 26.6% increase in TPH removal efficiency respectively. In contrast, inoculation of hydrocarbon degrading microorganisms only slightly enhanced the contaminant removal (increased 7.3%). The biopile with stronger contaminant removal also had higher pile temperature and lower pile pH (e.g., in "DW + M + BA + N"). GC-MS analysis shows that biopiling significantly reduced the total number of detected contaminants and changed the chemical composition. Overall, this study shows that biopiling is an effective remediation technology for drilling waste. Adding inorganic nutrients and bulking agents can significantly improve biopile performance while addition of microbial inocula had minimal positive impacts on contaminant removal. PMID- 26891353 TI - Simultaneous Cr(VI) removal and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) biodegradation by Pseudomonas aeruginosa in liquid medium. AB - Simultaneous Cr(VI) removal and 2,2',4,4'-tetra brominated diphenyl ether (BDE 47) biodegradation by Pseudomonas aeruginosa in liquid medium were investigated in this study, with the goal of elucidating the interaction between concomitant pollutants Cr(VI) and BDE-47 during microbial remediation. The experimental results revealed that the degradation efficiency of 1 mg L(-1) BDE-47 by 60 mg L( 1) biomass achieved 51.3% within 7 d when 2 mg L(-1) Cr(VI) coexisted. The degradation efficiency was accelerated at low concentrations of Cr(VI) (<=5 mg L( 1)), but inhibited at higher levels (>=10 mg L(-1)). Cr(VI) of 2 mg L(-1) facilitated the secretion of rhamnolipid from the strain, altered cell surface hydrophobicity and cell membrane permeability, and promoted intracellular BDE-47 accumulation, thus improving BDE-47 biotransformation. In addition, the stimulation of intracellular enzyme synthesis by 2 mg L(-1) Cr(VI) contributed to more BDE-47 elimination in the cells. The achievement of BDE-47 biodegradation was coupled with cell growth, enzyme extraction, cell membrane permeability change, and ATPase activity increase. The study also indicated that the improvement of Cr(VI) removal in BDE-47/Cr(VI) co-contaminated condition was mostly due to the increasing synthesis of extracellular enzyme in the presence of low concentrations of BDE-47. The whole study demonstrated that P. aeruginosa was available for the removal of toxic Cr(VI) and degradation of BDE-47 simultaneously in the liquid. PMID- 26891350 TI - Large-Scale Assessment of a Fully Automatic Co-Adaptive Motor Imagery-Based Brain Computer Interface. AB - In the last years Brain Computer Interface (BCI) technology has benefited from the development of sophisticated machine leaning methods that let the user operate the BCI after a few trials of calibration. One remarkable example is the recent development of co-adaptive techniques that proved to extend the use of BCIs also to people not able to achieve successful control with the standard BCI procedure. Especially for BCIs based on the modulation of the Sensorimotor Rhythm (SMR) these improvements are essential, since a not negligible percentage of users is unable to operate SMR-BCIs efficiently. In this study we evaluated for the first time a fully automatic co-adaptive BCI system on a large scale. A pool of 168 participants naive to BCIs operated the co-adaptive SMR-BCI in one single session. Different psychological interventions were performed prior the BCI session in order to investigate how motor coordination training and relaxation could influence BCI performance. A neurophysiological indicator based on the Power Spectral Density (PSD) was extracted by the recording of few minutes of resting state brain activity and tested as predictor of BCI performances. Results show that high accuracies in operating the BCI could be reached by the majority of the participants before the end of the session. BCI performances could be significantly predicted by the neurophysiological indicator, consolidating the validity of the model previously developed. Anyway, we still found about 22% of users with performance significantly lower than the threshold of efficient BCI control at the end of the session. Being the inter-subject variability still the major problem of BCI technology, we pointed out crucial issues for those who did not achieve sufficient control. Finally, we propose valid developments to move a step forward to the applicability of the promising co-adaptive methods. PMID- 26891354 TI - Improvement of tolerance to lead by filamentous fungus Pleurotus ostreatus HAU-2 and its oxidative responses. AB - Wastewater contaminated with heavy metals is a world-wide concern. One biological treatment strategy includes filamentous fungi capable of extracellular adsorption and intracellular bioaccumulation. Here we report that an acclimated strain of filamentous fungus Pleurotus ostreatus HAU-2 can withstand Pb up to 1500 mg L(-1) Pb, conditions in which the wildtype strain cannot grow. The acclimated strain grew in liquid culture under 500 mg L(-1) Pb without significant abnormity in biomass and morphology, and was able to remove significant amounts of heavy metals with rate of 99.1% at 200 mg L(-1) and 63.3% at 1500 mg L(-1). Intracellular bioaccumulation as well as extracellular adsorption both contributed the Pb reduction. Pb induced levels of H2O2, and its concentration reached 72.9-100.9 MUmol g(-1) under 200-1000 mg L(-1) Pb. A relatively higher malonaldehyde (MDA) concentration (8.06-7.59 nmol g(-1)) was also observed at 500 1500 mg L(-1) Pb, indicating that Pb exposure resulted in oxidative damage. The fungal cells also defended against the attack of reactive oxygen species by producing antioxidants. Of the three antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), CAT was the most responsive and the maximal enzyme activity was 15.8 U mg(-1) protein. Additionally, glutathione (GSH) might also play a role (3.16-3.21 mg g(-1) protein) in detoxification under relatively low Pb concentration (100-200 mg L(-1)). Our findings suggested that filamentous fungus could be selected for increased tolerance to heavy metals and that CAT and GSH might be important components of this tolerance. PMID- 26891356 TI - Influence of activated carbon preloading by EfOM fractions from treated wastewater on adsorption of pharmaceutically active compounds. AB - In this study, the preloading effects of different fractions of wastewater effluent organic matter (EfOM) on the adsorption of trace-level pharmaceutically active compounds (PhACs) onto granular activated carbon (GAC) were investigated. A nanofiltration (NF) membrane was employed to separate the EfOM by size, and two GACs with distinct pore structures were chosen for comparison. The results showed that preloading with EfOM substantially decreased PhAC uptake of the GACs; however, comparable PhAC adsorption capacities were achieved on GACs preloaded by feed EfOM and the NF-permeating EfOM. This indicates that: (1) the NF-rejected, larger EfOM molecules with an expectation to block the PhAC adsorption pores exerted little impact on the adsorbability of PhACs; (2) the smaller EfOM molecules present in the NF permeate contributed mainly to the decrease in PhAC uptake, mostly due to site competition. Of the two examined GACs, the wide pore size-distributed GAC was found to be more susceptible to EfOM preloading than the microporous GAC. Furthermore, among the fourteen investigated PhACs, the negatively charged hydrophilic PhACs were generally subjected to a greater EfOM preloading impact. PMID- 26891355 TI - Efficient degradation of Acid Orange 7 in aqueous solution by iron ore tailing Fenton-like process. AB - An effective method based on iron ore tailing Fenton-like process was studied for removing an azo dye, Acid Orange 7 (AO7) in aqueous solution. Five tailings were characterized by X-ray fluorescence spectroscope (XFS), Brunner-Emmet-Teller (BET) measurement, and Scanning Electron Microscope (SEM). The result of XFS showed that Fe, Si and Ca were the most abundant elements and some toxic heavy metals were also present in the studied tailings. The result of BET analysis indicated that the studied tailings had very low surface areas (0.64-5.68 m(2) g( 1)). The degradation efficiencies of AO7 were positively correlated with the content of iron oxide and cupric oxide, and not related with the BET surface area of the tailings. The co-existing metal elements, particularly Cu, might accelerate the heterogeneous Fenton-like reaction. The effects of other parameters on heterogeneous Fenton-like degradation of AO7 by a converter slag iron tailing (tailing E) which contains highest iron oxide were also investigated. The tailing could be reused 10 times without significant decrease of the catalytic capacity. Very low amount of iron species and almost undetectable toxic elements were leached in the catalytic degradation of AO7 by the tailing E. The reaction products were identified by gas chromatography-mass spectrometry and a possible pathway of AO7 degradation was proposed. This study not only provides an effective method for removing azo dyes in polluted water by employing waste tailings as Fenton-like catalysts, but also uses waste tailings as the secondary resource. PMID- 26891357 TI - Chemical speciation of cadmium: An approach to evaluate plant-available cadmium in Ecuadorian soils under cacao production. AB - Elevated concentration of cadmium (Cd) in cacao beans has raised serious concerns about the chocolate consumption on human health. Accumulation of Cd in cacao bean in southern Ecuador has been related to soil contamination. In this study, soil fractionation approach was used to identify available Cd pools in the soils and to correlate these Cd pools with bean Cd concentration and soil test indexes. The distribution of soil Cd fractions decreased in the order: oxidizable > acid soluble > residual > reducible >> water-soluble (+exchangeable). Oxidizable and acid-soluble fractions accounted for 59 and 68% of the total recoverable Cd for the 0-5 and 5-15 cm soil depth, respectively. Acid-soluble fraction was closely related to bean-Cd, with correlation coefficients (r) of 0.70 and 0.81 (P < 0.01) for the 0-5 and 5-15 cm soil depth, respectively. Acid-soluble Cd was significantly correlated with 0.01 M HCl- (r = 0.99, P < 0.01) or Mehlich 3- extractable Cd (r = 0.97, P < 0.01). These results indicate that acid-soluble Cd fraction is an important part of available Cd pool. Since approximately 60% of Cd in the cacao-growing soils is related to the acid-soluble fraction and bound to organic matter, remediation of the contaminated soils should consider to the dynamics of soil pH and organic matter content. PMID- 26891358 TI - The influences of dissolved organic matter and surfactant on the desorption of Cu and Zn from road-deposited sediment. AB - This study showcases the desorption behaviours of copper (Cu) and zinc (Zn) in road-deposited sediment (RDS). Batch tests were conducted to investigate the influences of rainwater, major wastewater constituents of dissolved organic matter (DOM) and surfactant on the metals leaching from RDS. Results show that the rainwater solutions considerably enhanced the total amounts of Cu (319 +/- 46% of the total leaching amount by blank solutions) and Zn (617 +/- 130%) released from RDS compared with blank solutions. DOM enhanced the leaching of Cu from RDS at a neutral pH. By contrast, DOM had an adverse effect on the mobilization of Zn. In the absence of DOM, a higher concentration of sodium dodecyl sulfonate (SDS) slightly increased the release of Cu from RDS than a lower concentration of SDS. However, the existence of SDS suppressed the release of Zn from RDS. PMID- 26891359 TI - Evidence for the generation of reactive oxygen species from hydroquinone and benzoquinone: Roles in arsenite oxidation. AB - Natural organic matter (NOM) significantly affects the fate, bioavailability, and toxicity of arsenic in the environment. In the present study, we investigated the oxidation of As(III) in the presence of hydroquinone (HQ) and benzoquinone (BQ), which were selected as model quinone moieties for NOM. It was found that As(III) was oxidized to As(V) in the presence of HQ or BQ at neutral conditions, and the oxidation efficiency of As(III) increased from 33% to 92% in HQ solutions and from 0 to 80% in BQ solutions with pH increasing from 6.5 to 8.5. The oxidation mechanism was further explored with electron spin resonance (ESR) technique. The results showed that semiquinone radicals (SQ(-)) were generated from the comproportionation reaction between BQ and HQ, which mediated the formation of superoxide anion (O2(-)), hydrogen peroxide (H2O2) and hydroxyl radical (OH). Both the SQ(-), H2O2 and OH contributed to the oxidation of As(III). The increase of pH favored the formation of SQ(-), and thus promoted the generation of reactive oxygen species (ROS) as well as As(III) oxidation. Increasing concentrations of HQ and BQ from 0.1 to 1.0 mM enhanced As(III) oxidation from 65% to 94% and from 10% to 53%, respectively. The findings of this study facilitate our understanding of the fate and transformation of As(III) in organic rich aquatic environments and highlight quinone moieties as the potential oxidants for As(III) in the remediation of arsenic contaminated sites. PMID- 26891361 TI - Abiotic degradation of methyl parathion by manganese dioxide: Kinetics and transformation pathway. AB - Methyl parathion, a widely used insecticide around the world, has aroused gradually extensive concern of researchers due to its degradation product such as methyl paraoxon, with higher toxicity for mammals and more recalcitrant. Given the ubiquity of manganese dioxide (MnO2) in soils and aquatic sediments, the abiotic degradation of methyl parathion by alpha-MnO2 was investigated in batch experiments. It was found that methyl parathion was decomposed up to 90% by alpha MnO2 in 30 h and the removal efficiency of methyl parathion depended strongly on the loading of alpha-MnO2 and pH value in the solution where the reactions followed pseudo-first-order model well. The coexisting metal ions (such as Ca(2+), Mg(2+) and Mn(2+)) weakened markedly the degradation of methyl parathion by alpha-MnO2. However, the effect of dissolved organic matter (HA-Na) on reaction rates presented two sides: to improve hydrolysis rate but deteriorate oxidation rate of methyl parathion. Based on the degradation products identified by gas chromatography-mass spectrometer (GC/MS) and liquid chromatography high resolution mass spectrometer (LC/HRMS), both hydrolysis and oxidation processes were proposed to be two predominant reaction mechanisms contributing to methyl parathion degradation by alpha-MnO2. This study provided meaningful information to elucidate the abiotic dissipation of methyl parathion by manganese oxide minerals in the environment. PMID- 26891360 TI - The importance of evaluating metal exposure and predicting human health risks in urban-periurban environments influenced by emerging industry. AB - The human population boom, urbanization and rapid industrialization have either directly or indirectly resulted in the serious environmental toxification of the soil-food web by metal exposure from anthropogenic sources in most of the developing industrialized world. The present study was conducted to analyze concentrations of Cd, Cr, Cu, Mn, Ni, Pb, and Zn in soil and vegetables in the urban-periurban areas influenced by emerging industry. Vegetables and their corresponding soil samples were collected and analyzed for heavy metals contents from six random sites. According to the results, the potential health risks from metals to the local communities were assessed by following the methodology described by the US-EPA. In general, the total non-carcinogenic risks were shown to be less than the limits set by the US-EPA. However, the potential risk of developing carcinogenicity in humans over a lifetime of exposure could be increased through the dietary intake of Cd, Cr and Ni. In some cases, Pb was also marginally higher than the safe level. It was concluded that some effective remedial approaches should be adopted to mitigate the risks of Cd, Cr, Ni and Pb in the study area because these metal levels have exceeded the safe limits for human health. However, new studies on gastrointestinal bioaccessibility in human are required to heighten our understanding about metals exposure and health risk assessment. PMID- 26891362 TI - Effects of source rocks, soil features and climate on natural gamma radioactivity in the Crati valley (Calabria, Southern Italy). AB - The study, which represents an innovative scientific strategy to approach the study of natural radioactivity in terms of spatial and temporal variability, was aimed to characterize the background levels of natural radionuclides in soil and rock in the urban and peri-urban soil of a southern Italy area; to quantify their variations due to radionuclide bearing minerals and soil properties, taking into account nature and extent of seasonality influence. Its main novelty is taking into account the effect of climate in controlling natural gamma radioactivity as well as analysing soil radioactivity in terms of soil properties and pedogenetic processes. In different bedrocks and soils, activities of natural radionuclides ((238)U, (232)Th (4) K) and total radioactivity were measured at 181 locations by means of scintillation gamma-ray spectrometry. In addition, selected rocks samples were collected and analysed, using a Scanning Electron Microscope (SEM) equipped with an Energy Dispersive Spectrometer (EDS) and an X-Ray Powder Diffraction (XRPD), to assess the main sources of radionuclides. The natural gamma background is intimately related to differing petrologic features of crystalline source rocks and to peculiar pedogenetic features and processes. The radioactivity survey was conducted during two different seasons with marked changes in the main climatic characteristics, namely dry summer and moist winter, to evaluate possible effects of seasonal climatic variations and soil properties on radioactivity measurements. Seasonal variations of radionuclides activities show their peak values in summer. The activities of (238)U, (232)Th and (4) K exhibit a positive correlation with the air temperature and are negatively correlated with precipitations. PMID- 26891363 TI - Monitoring Therapy Compliance of Tuberculosis Patients by using Video-Enabled Electronic Devices. AB - A recent innovation to help patients adhere to daily tuberculosis (TB) treatment over many months is video (or virtually) observed therapy (VOT). VOT is becoming increasingly feasible as mobile telephone applications and tablet computers become more widely available. Studies of the effectiveness of VOT in improving TB patient outcomes are being conducted. PMID- 26891367 TI - A One-Structure-Based Hybridized Nanogenerator for Scavenging Mechanical and Thermal Energies by Triboelectric-Piezoelectric-Pyroelectric Effects. AB - A hybridized nanogenerator is demonstrated, which has the structure of PVDF nanowires-PDMS composite film/indium tin oxide (ITO) electrode/polarized PVDF film/ITO electrode, and which can individually/simultaneously scavenge mechanical and thermal energies using piezoelectric, triboelectric, and pyroelectric effects. As compared with the individual energy harvesting unit, the hybridized nanogenerator has a much better charging performance. This work may push forward a significant step toward multienergy harvesting technology. PMID- 26891364 TI - Prediction of Certain Well-Characterized Domains of Known Functions within the PE and PPE Proteins of Mycobacteria. AB - The PE and PPE protein family are unique to mycobacteria. Though the complete genome sequences for over 500 M. tuberculosis strains and mycobacterial species are available, few PE and PPE proteins have been structurally and functionally characterized. We have therefore used bioinformatics tools to characterize the structure and function of these proteins. We selected representative members of the PE and PPE protein family by phylogeny analysis and using structure-based sequence annotation identified ten well-characterized protein domains of known function. Some of these domains were observed to be common to all mycobacterial species and some were species specific. PMID- 26891366 TI - Down syndrome: perinatal mortality risks with each additional week of expectant management. AB - OBJECTIVE: To evaluate the gestational age (GA) at which perinatal mortality risk is minimized for fetuses with Down syndrome (DS). METHODS: Retrospective cohort of singleton pregnancies delivered between 24 and 41 weeks, using 2005-2006 United States linked birth and death certificate data. Among fetal DS cases, prospective risk of intrauterine fetal demise (IUFD) and risk of infant death were calculated for each week, and composite risk of fetal/infant mortality with expectant management was compared to delivery. RESULTS: Of 3,113,098 pregnancies, 1766 had fetal DS (0.06%). IUFD occurred in 7.4% with DS, and infant death in 6.5%. Prospective risk of IUFD increased from 37 weeks onward to reach 50.7 per 1000 pregnancies (95% CI 33.2-68.3) at 42 weeks. Comparing mortality with expectant management to delivery, expectant management carried increasing risk from 38 (RR 1.18; 95% CI 1.05-1.33) to 41 weeks (RR 1.84; 95% CI 1.66-2.05). Further, number needed to deliver to avoid one excess death decreased from 38 (109.17; 95% CI 64.52-344.83) to 41 weeks (24.08; 95% CI 20.59-29.04). CONCLUSIONS: Although further research is needed to clarify risk factors for fetal and neonatal death in cases of DS, risk of perinatal mortality appears to be minimized with delivery at 38 weeks. PMID- 26891365 TI - Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism. AB - Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and beta-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID- 26891368 TI - An Unusual Cause of Altered Mental Status: Recurrent Cerebral Air Embolism. PMID- 26891369 TI - Dressings Loaded with Cyclodextrin-Hamamelitannin Complexes Increase Staphylococcus aureus Susceptibility Toward Antibiotics Both in Single as well as in Mixed Biofilm Communities. AB - Bacteria reside within biofilms at the infection site, making them extremely difficult to eradicate with conventional wound care products. Bacteria use quorum sensing (QS) systems to regulate biofilm formation, and QS inhibitors (QSIs) have been proposed as promising antibiofilm agents. Despite this, few antimicrobial therapies that interfere with QS exist. Nontoxic hydroxypropyl-beta-cyclodextrin functionalized cellulose gauzes releasing a burst of the antibiotic vancomycin and the QSI hamamelitannin are developed, followed by a sustained release of both. The gauzes affect QS and biofilm formation of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro model of chronic wound infection and can be considered as candidates to be used to prevent wound infection as well as treat infected wounds. PMID- 26891370 TI - Radioiodine therapy versus antithyroid medications for Graves' disease. AB - BACKGROUND: Graves' disease is the most common cause of hyperthyroidism. Both antithyroid medications and radioiodine are commonly used treatments but their frequency of use varies between regions and countries. Despite the commonness of the diagnosis, any possible differences between the two treatments with respect to long-term outcomes remain unknown. OBJECTIVES: To assess the effects of radioiodine therapy versus antithyroid medications for Graves' disease. SEARCH METHODS: We performed a systematic literature search in the Cochrane Library, MEDLINE and EMBASE and the trials registers ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was September 2015 for all databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of radioiodine therapy versus antithyroid medications for Graves' disease with at least two years follow-up. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for relevance. One author carried out screening for inclusion, data extraction and 'Risk of bias' assessment and a second author checked this. We presented data not suitable for meta-analysis as descriptive data. We analysed the overall quality of evidence utilising the GRADE instrument. MAIN RESULTS: We included two RCTs involving 425 adult participants with Graves' disease in this review. Altogether 204 participants were randomised to radioiodine therapy and 221 to methimazole therapy. A single dose of radioiodine was administered. The duration of methimazole medication was 18 months. The period of follow-up was at least two years, depending on the outcome measured. For most outcome measures risk of bias was low; for the outcomes health related quality of life as well as development and worsening of Graves' ophthalmopathy risks of performance bias and detection bias were high in at least one of the two RCTs.Health-related quality of life appeared to be similar in the radioiodine and methimazole treatment groups, however no quantitative data were reported (425 participants; 2 trials; low quality evidence). The development and worsening of Graves' ophthalmopathy was observed in 76 of 202 radioiodine-treated participants (38%) and in 40 of 215 methimazole-treated participants (19%): risk ratio (RR) 1.94 (95% confidence interval (CI) 1.40 to 2.70); 417 participants; 2 trials; low quality evidence. A total of 35% to 56% of radioiodine-treated participants and 42% of participants treated with methimazole were smokers, which is associated with the risk of worsening or development of Graves' ophthalmopathy. Euthyroidism was not achieved by any participant being treated with radioiodine compared with 64/68 (94%) of participants after methimazole treatment (112 participants; 1 trial). In this trial thyroxine therapy was not introduced early in both treatment arms to avoid hypothyroidism. Recurrence of hyperthyroidism (relapse) in favour of radioiodine treatment showed a RR of 0.20 (95% CI 0.01 to 2.66); P value = 0.22; 417 participants; 2 trials; very low quality evidence. Heterogeneity was high (I2 = 91%) and the RRs were 0.61 or 0.06 with non-overlapping CIs. Adverse events other than development of worsening of Graves' ophthalmopathy for radioiodine therapy were hypothyroidism (39 of 41 participants (95%) compared with 0% of participants receiving methimazole, however thyroxine treatment to avoid hypothyroidism was not introduced early in the radioiodine group - 104 participants; 1 trial; very low quality evidence) and drug-related adverse events for methimazole treatment (23 of 215 participants (11%) reported adverse effects likely related to methimazole therapy - 215 participants; 2 trials; very low quality evidence). The outcome measures all cause mortality and bone mineral density were not reported in the included trials. One trial (174 participants) reported socioeconomic effects: costs based on the official hospital reimbursement system in Sweden for patients without relapse and methimazole treatment were USD 1126/1164 (young/older methimazole group) and for radioiodine treatment USD 1862. Costs for patients with relapse and methimazole treatment were USD 2284/1972 (young/older methimazole group) and for radioiodine treatment USD 2760. AUTHORS' CONCLUSIONS: The only antithyroid drug investigated in the two included trials was methimazole, which might limit the applicability of our findings with regard to other compounds such as propylthiouracil. Results from two RCTs suggest that radioiodine treatment is associated with an increased risk of Graves' ophthalmopathy. Our findings suggest some benefit from radioiodine treatment for recurrence of hyperthyroidism (relapse) but there is uncertainty about the magnitude of the effect size. PMID- 26891371 TI - Modulating myosin restores muscle function in a mouse model of nemaline myopathy. AB - OBJECTIVE: Nemaline myopathy, one of the most common congenital myopathies, is associated with mutations in various genes including ACTA1. This disease is also characterized by various forms/degrees of muscle weakness, with most cases being severe and resulting in death in infancy. Recent findings have provided valuable insight into the underlying pathophysiological mechanisms. Mutations in ACTA1 directly disrupt binding interactions between actin and myosin, and consequently the intrinsic force-generating capacity of muscle fibers. ACTA1 mutations are also associated with variations in myofiber size, the mechanisms of which have been unclear. In the present study, we sought to test the hypotheses that the compromised functional and morphological attributes of skeletal muscles bearing ACTA1 mutations (1) would be directly due to the inefficient actomyosin complex and (2) could be restored by manipulating myosin expression. METHODS: We used a knockin mouse model expressing the ACTA1 His40Tyr actin mutation found in human patients. We then performed in vivo intramuscular injections of recombinant adeno associated viral vectors harboring a myosin transgene known to facilitate muscle contraction. RESULTS: We observed that in the presence of the transgene, the intrinsic force-generating capacity was restored and myofiber size was normal. INTERPRETATION: This demonstrates a direct link between disrupted attachment of myosin molecules to actin monomers and muscle fiber atrophy. These data also suggest that further therapeutic interventions should primarily target myosin dysfunction to alleviate the pathology of ACTA1-related nemaline myopathy. Ann Neurol 2016;79:717-725. PMID- 26891372 TI - Intermittent Intraoperative Neural Monitoring Technology in Minimally Invasive Video-Assisted Thyroidectomy: A Preliminary Study. AB - PURPOSE: Intraoperative neural monitoring (IONM) technology was applied in minimally invasive video-assisted thyroidectomy (MIVAT) to explore its safety and effectiveness. MATERIALS AND METHODS: Data were collected retrospectively from October 2009 to August 2011. Inclusion criteria included the following: (1) benign thyroid nodule with maximum diameter less than 4.0 cm by preoperative ultrasound evaluation; (2) no previous thyroid surgeries; (3) no cervical radiation history; (4) normal function of recurrent laryngeal nerve (RLN) examined by preoperative laryngoscopy; (5) patients who did not accept to take a "wait and see" follow-up strategy. Enrolled patients were randomly allocated into NIM group and control group. RESULTS: 46 patients were enrolled in NIM group, and 51 patients were enrolled in control group. All surgeries in NIM group were performed successfully, and majority of tracheal intubations were placed with one attempt. 47 RLNs in NIM group and 60 RLNs in control group were exposed. The time of RLN locating was 6.06 +/- 1.48 min in NIM group and 6.92 +/- 1.34 min in control group (p = .02). The time of RLN tracing and exposing was 28.96 +/- 4.75 min in NIM group and 32.17 +/- 5.56 min in control group (p = .02). 1 case of temporary RLN paralysis was observed in both groups, and no permanent RLN paralysis was reported. CONCLUSIONS: The application of intermittent IONM in MIVAT is feasible. Intermittent IONM can help reduce the time of RLN locating and the time of RLN tracing and exposing. PMID- 26891373 TI - Serum myeloid-related protein 8/14 in minimal change- and glomerulonephritis related nephrotic syndrome. AB - BACKGROUND: Myeloid-related protein 8/14 (MRP8/14) forms stable heterodimers and is the major calcium-binding protein secreted by activated granulocytes and monocytes. We evaluated whether serum MRP8/14 level is a useful indicator for a differential diagnosis of glomerulonephritis (GN)- and minimal change disease (MC)- related nephrotic syndrome (NS). METHODS: Serum MRP8/14 complex was evaluated in 37 NS patients with MC or GN. These patients were divided into two groups. Group 1 consisted of 13 NS patients with MC, and group 2 consisted of 24 NS patients with GN. Group 2 was further divided into four subgroups: IgA nephropathy (IgAN; n = 5), Henoch-Schonlein purpura nephritis (HSPN; n = 6), focal segmental glomerulosclerosis (FSGS; n = 12), and acute GN Poststreptococcal acute glomeruloNephritis (PSAGN; n = 1). RESULTS: The clinical manifestations, laboratory findings, serum MRP8/14 level, and renal accumulation of MRP8 were investigated for each group. No significant inter-group differences were observed for serum total protein, serum albumin, or blood urea nitrogen and urinary protein excretions. Mean serum MRP8/14 in the IgAN, HSPN, FSGS, and PSAGN groups was higher than in group 1. Further, the mean glomerular and interstitial MRP8 staining scores in the IgAN, HSPN, and PSAGN groups were higher than in group 1. CONCLUSIONS: Serum MRP8/14 level may be a useful indicator for differential diagnosis between GN- and MC- related NS. PMID- 26891375 TI - Alleviating anemia and thrombocytopenia in myelofibrosis patients. AB - Anemia and thrombocytopenia are frequent clinical manifestations of myelofibrosis as well as important prognostic factors of the disease. Concerning the treatment of anemia, the first step should be the correction of reversible contributing factors, such as possible iron, folate and vitamin B12 deficiency. Then, treatment options include erythropoiesis stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy. Anemia responses may also be observed in some patients treated with JAK inhibitors. However, most patients eventually fail to such therapies and become transfusion dependent. Some of the aforementioned therapies can also improve thrombocytopenia, but the responses are usually observed in patients with moderate platelet count decrease. Allogeneic hematopoietic stem cell transplantation, the only curative treatment of myelofibrosis, can be an alternative for selected patients with cytopenias who are refractory to conventional therapies. However, for the majority of patients, the management of anemia and severe thrombocytopenia remains an unmet need. PMID- 26891374 TI - Correction of Mutant p63 in EEC Syndrome Using siRNA Mediated Allele-Specific Silencing Restores Defective Stem Cell Function. AB - Ectrodactyly-Ectodermal dysplasia-Clefting (EEC) syndrome is a rare autosomal dominant disease caused by heterozygous mutations in the p63 gene and characterized by limb defects, orofacial clefting, ectodermal dysplasia, and ocular defects. Patients develop progressive total bilateral limbal stem cell deficiency, which eventually results in corneal blindness. Medical and surgical treatments are ineffective and of limited benefit. Oral mucosa epithelial stem cells (OMESCs) represent an alternative source of stem cells capable of regenerating the corneal epithelium and, combined with gene therapy, could provide an attractive therapeutic avenue. OMESCs from EEC patients carrying the most severe p63 mutations (p.R279H and p.R304Q) were characterized and the genetic defect of p.R279H silenced using allele-specific (AS) small interfering RNAs (siRNAs). Systematic screening of locked nucleic acid (LNA)-siRNAs against R279H-p63 allele in (i) stable WT-DeltaNp63alpha-RFP and R279H-DeltaNp63alpha EGFP cell lines, (ii) transient doubly transfected cell lines, and (iii) p.R279H OMESCs, identified a number of potent siRNA inhibitors for the mutant allele, which had no effect on wild-type p63. In addition, siRNA treatment led to longer acquired life span of mutated stem cells compared to controls, less accelerated stem cell differentiation in vitro, reduced proliferation properties, and effective ability in correcting the epithelial hypoplasia, thus giving rise to full thickness stratified and differentiated epithelia. This study demonstrates the phenotypic correction of mutant stem cells (OMESCs) in EEC syndrome by means of siRNA mediated AS silencing with restoration of function. The application of siRNA, alone or in combination with cell-based therapies, offers a therapeutic strategy for corneal blindness in EEC syndrome. Stem Cells 2016;34:1588-1600. PMID- 26891376 TI - Is Intracranial Pressure Monitoring of Patients With Diffuse Traumatic Brain Injury Valuable? An Observational Multicenter Study. AB - BACKGROUND: Although intracranial pressure (ICP) monitoring of patients with severe traumatic brain injury (TBI) is recommended by the Brain Trauma Foundation, any benefits remain controversial. OBJECTIVE: To evaluate the effects of ICP monitoring on the mortality of and functional outcomes in patients with severe diffuse TBI. METHODS: Data were collected on patients with severe diffuse TBI (Glasgow Coma Scale [GCS] score on admission <9 and Marshall Class II-IV) treated from January 2012 to December 2013 in 24 hospitals (17 level I trauma centers and 7 level II trauma centers) in 9 Chinese provinces. We evaluated the impact of ICP monitoring on 6-month mortality and favorable outcome using propensity score-matched analysis after controlling for independent predictors of these outcomes. RESULTS: ICP monitors were inserted into 287 patients (59.5%). After propensity score matching, ICP monitoring significantly decreased 6-month mortality. ICP monitoring also had a greater impact on the most severely injured patients on the basis of head computed tomography data (Marshall computed tomography classification IV) and on patients with the lowest level of consciousness (GCS scores 3-5). After propensity score matching, monitoring remained nonassociated with a 6-month favorable outcome for the overall sample. However, monitoring had a significant impact on the 6-month favorable outcomes of patients with the lowest level of consciousness (GCS scores 3-5). CONCLUSION: ICP monitor placement was associated with a significant decrease in 6-month mortality after adjustment for the baseline risk profile and the monitoring propensity of patients with diffuse severe TBI, especially those with GCS scores of 3 to 5 or of Marshall computed tomography classification IV. PMID- 26891377 TI - A Phase III Clinical Trial Showing Limited Efficacy of Autologous Mesenchymal Stem Cell Therapy for Spinal Cord Injury. AB - BACKGROUND: In our previous report, 3 of 10 patients with spinal cord injury who were injected with autologous mesenchymal stem cells (MSCs) showed motor improvement in the upper extremities and in activities of daily living. OBJECTIVE: To report on the results of a phase III clinical trial of autologous MSCs therapy. METHODS: Patients were selected based on the following criteria: chronic American Spinal Injury Association B status patients who had more than 12 months of cervical injury, and no neurological changes during the recent 3 months of vigorous rehabilitation. We injected 1.6 * 10 autologous MSCs into the intramedullary area at the injured level and 3.2 * 10 autologous MSCs into the subdural space. Outcome data were collected over 6 months regarding neurological examination, magnetic resonance imaging with diffusion tensor imaging, and electrophysiological analyses. RESULTS: Among the 16 patients, only 2 showed improvement in neurological status (unilateral right C8 segment from grade 1 to grade 3 in 1 patient and bilateral C6 from grade 3 to grade 4 and unilateral right C8 from grade 0 to grade 1 in 1 patient). Both patients with neurological improvement showed the appearance of continuity in the spinal cord tract by diffusion tensor imaging. There were no adverse effects associated with MSCs injection. CONCLUSION: Single MSCs application to intramedullary and intradural space is safe, but has a very weak therapeutic effect compared with multiple MSCs injection. Further clinical trials to enhance the effect of MSCs injection are necessary. PMID- 26891379 TI - Relationship Between Biotype and Bone Morphology in the Lower Anterior Mandible: An Observational Study. AB - BACKGROUND: Different clinical parameters have been advocated as potential predictors of alveolar and basal jawbone morphology. The aim of this study is to describe, by tomographic means, alveolar and basal osseous dimensions of the anterior mandible in healthy individuals and evaluate potential correlations with biotype, along with other clinical parameters. METHODS: One hundred consecutive healthy patients needing surgery in the posterior mandible were enrolled in this observational study (group 1 = 50 patients with thin biotype; group 2 = 50 patients with thick biotype). Data were collected for: 1) Little irregularity index for anterior crowding; 2) molar and canine class relationship; 3) previous orthodontic treatment; 4) gingival recession; and 5) band of keratinized gingiva for each of the six anterior mandibular teeth (#22 through #27). At the most mid buccal computerized tomography slice of each tooth, other parameters were measured, including: 1) distance from the cemento-enamel junction to the bone crest; 2) tooth torque (TT); 3) labial cortical bone thickness (BT) for alveolar and basal bone; and 4) BT 5 and 10 mm apical to the tooth apex. Data were statistically analyzed, and significance was set at P <=0.05. RESULTS: Mean thickness of alveolar bone ranged from 6.66 to 4.51 mm (standard deviation [SD] = 1.46 for tooth #27; SD = 1.01 for tooth #25) whereas mean thickness of basal bone ranged from 8.9 to 8.2 mm (SD = 2.06 for tooth #22; SD = 2.06 for tooth #26). Mean thickness of bone at 5 mm from apex ranged from 11.94 to 10.47 mm (SD = 2.96 for tooth #25; SD = 2.22 for tooth #22), whereas mean thickness of bone at 10 mm from apex ranged from 13.75 to 11.08 mm (SD = 2.79 for tooth #25; SD = 2.53 for tooth #27). No statistically significant differences were detected among biotypes, whereas: 1) TT, 2) age, and 3) smoking habit were often predictors of reduction in BT in a multiple linear regression model. Male sex was often a predictor of positive changes in BT, and previous orthodontic therapy was a protective factor against developing bone loss >5 mm. CONCLUSIONS: Although some differences were detected among biotypes, data indicate that biotype does not play a fundamental role in influencing alveolar BT, whereas other variables (i.e., TT, sex, age, and smoking habit) do influence alveolar BT. Further studies are needed to better understand the extent of influence of each clinical variable. PMID- 26891381 TI - Percolative switching in transition metal dichalcogenide field-effect transistors at room temperature. AB - We have addressed the microscopic transport mechanism at the switching or 'on off' transition in transition metal dichalcogenide (TMDC) field-effect transistors (FETs), which has been a controversial topic in TMDC electronics, especially at room temperature. With simultaneous measurement of channel conductivity and its slow time-dependent fluctuation (or noise) in ultrathin WSe2 and MoS2 FETs on insulating SiO2 substrates where noise arises from McWhorter type carrier number fluctuations, we establish that the switching in conventional backgated TMDC FETs is a classical percolation transition in a medium of inhomogeneous carrier density distribution. From the experimentally observed exponents in the scaling of noise magnitude with conductivity, we observe unambiguous signatures of percolation in a random resistor network, particularly, in WSe2 FETs close to switching, which crosses over to continuum percolation at a higher doping level. We demonstrate a powerful experimental probe to the microscopic nature of near-threshold electrical transport in TMDC FETs, irrespective of the material detail, device geometry, or carrier mobility, which can be extended to other classes of 2D material-based devices as well. PMID- 26891380 TI - Decompressive laparotomy for abdominal compartment syndrome. AB - BACKGROUND: The effect of decompressive laparotomy on outcomes in patients with abdominal compartment syndrome has been poorly investigated. The aim of this prospective cohort study was to describe the effect of decompressive laparotomy for abdominal compartment syndrome on organ function and outcomes. METHODS: This was a prospective cohort study in adult patients who underwent decompressive laparotomy for abdominal compartment syndrome. The primary endpoints were 28-day and 1-year all-cause mortality. Changes in intra-abdominal pressure (IAP) and organ function, and laparotomy-related morbidity were secondary endpoints. RESULTS: Thirty-three patients were included in the study (20 men). Twenty-seven patients were surgical admissions treated for abdominal conditions. The median (i.q.r.) Acute Physiology And Chronic Health Evaluation (APACHE) II score was 26 (20-32). Median IAP was 23 (21-27) mmHg before decompressive laparotomy, decreasing to 12 (9-15), 13 (8-17), 12 (9-15) and 12 (9-14) mmHg after 2, 6, 24 and 72 h. Decompressive laparotomy significantly improved oxygenation and urinary output. Survivors showed improvement in organ function scores, but non-survivors did not. Fourteen complications related to the procedure developed in eight of the 33 patients. The abdomen could be closed primarily in 18 patients. The overall 28-day mortality rate was 36 per cent (12 of 33), which increased to 55 per cent (18 patients) at 1 year. Non-survivors were no different from survivors, except that they tended to be older and on mechanical ventilation. CONCLUSION: Decompressive laparotomy reduced IAP and had an immediate effect on organ function. It should be considered in patients with abdominal compartment syndrome. PMID- 26891383 TI - Focus on Physiology to Improve Cardiopulmonary Resuscitation. PMID- 26891384 TI - Midazolam for Anxiolysis and Postoperative Nausea and Vomiting Prophylaxis: Can We Kill Two Birds with One Stone? PMID- 26891385 TI - Will Xenon Be a Valuable Addition in Perioperative and Critical Care Settings? PMID- 26891382 TI - Surface dynamics of voltage-gated ion channels. AB - Neurons encode information in fast changes of the membrane potential, and thus electrical membrane properties are critically important for the integration and processing of synaptic inputs by a neuron. These electrical properties are largely determined by ion channels embedded in the membrane. The distribution of most ion channels in the membrane is not spatially uniform: they undergo activity driven changes in the range of minutes to days. Even in the range of milliseconds, the composition and topology of ion channels are not static but engage in highly dynamic processes including stochastic or activity-dependent transient association of the pore-forming and auxiliary subunits, lateral diffusion, as well as clustering of different channels. In this review we briefly discuss the potential impact of mobile sodium, calcium and potassium ion channels and the functional significance of this for individual neurons and neuronal networks. PMID- 26891386 TI - Primus Inter Pares? The Angle of View Varies. PMID- 26891387 TI - Evolving Definitions and Pharmacologic Management of Complex Regional Pain Syndrome. PMID- 26891388 TI - 2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients After Transfusion. AB - BACKGROUND: Stored red blood cells (RBCs) are deficient in 2,3-diphosphoglycerate (2,3-DPG), but it is unclear how autologous salvaged blood (ASB) compares with stored blood and how rapidly 2,3-DPG levels return to normal after transfusion. Therefore, we compared levels of 2,3-DPG in stored versus ASB RBCs and in patients' blood after transfusion. METHODS: Twenty-four patients undergoing multilevel spine fusion surgery were enrolled. We measured 2,3-DPG and the oxyhemoglobin dissociation curve (P50) in samples taken from the ASB and stored blood bags before transfusion and in blood samples drawn from patients before and after transfusion. RESULTS: The mean storage duration for stored RBCs was 24 +/- 8 days. Compared with fresh RBCs, stored RBCs had decreased 2,3-DPG levels (by approximately 90%; P < 0.0001) and a decreased P50 (by approximately 30%; P < 0.0001). However, ASB RBCs did not exhibit these changes. The mean 2,3-DPG concentration decreased by approximately 20% (P < 0.05) in postoperative blood sampled from patients who received 1 to 3 stored RBC units and by approximately 30% (P < 0.01) in those who received >=4 stored RBC units. 2,3-DPG was unchanged in patients who received no stored blood or ASB alone. After surgery, 2,3-DPG levels recovered gradually over 3 postoperative days in patients who received stored RBCs. CONCLUSIONS: Stored RBCs, but not ASB RBCs, have decreased levels of 2,3-DPG and a left-shift in the oxyhemoglobin dissociation curve. Postoperatively, 2,3-DPG levels remain below preoperative baseline levels for up to 3 postoperative days in patients who receive stored RBCs but are unchanged in those who receive only ASB RBCs. PMID- 26891390 TI - High-Velocity Jet in the Right Atrium: What Is the Diagnosis? PMID- 26891389 TI - Imaging Artifacts in Echocardiography. AB - Artifacts are frequently encountered during echocardiographic examinations. An understanding of the physics and underlying assumptions of ultrasound processing involved with image generation is important for accurate interpretation of 2D grayscale, spectral Doppler, color flow Doppler, and 3D artifacts and their clinical implications. PMID- 26891391 TI - Transesophageal Echocardiogram-Guided Percutaneous AngioVac Extraction of a Right Atrial Embolus. PMID- 26891392 TI - Pharmacokinetics and Pharmacodynamics of Drugs Commonly Used in Pregnancy and Parturition. AB - The majority of pregnant women will be treated with a medication other than a vitamin supplement during their pregnancy. Almost half of these medications will be category C or D according to the former US Food and Drug Administration classification system, indicating a lack of human studies with animal studies suggesting adverse fetal effects (category C) or evidence of risk in humans (category D). Changes in maternal physiology alter drug bioavailability, distribution, clearance, and thus the drug half-life in often unpredictable ways. For many drugs, good pharmacokinetic and pharmacodynamic data in pregnancy and parturition are lacking. For other drugs, recent studies demonstrate major pharmacokinetic or pharmacodynamic changes that require dose adjustment in pregnancy, but current dosing guidelines do not reflect these data. In this review, we address the principles that underlie changes in pharmacology and physiology in pregnancy and provide information on drugs that anesthesiologists commonly encounter in treating pregnant patients. PMID- 26891394 TI - Limitations of Significance Testing in Clinical Research: A Review of Multiple Comparison Corrections and Effect Size Calculations with Correlated Measures. AB - Modern clinical research commonly uses complex designs with multiple related outcomes, including repeated-measures designs. While multiple comparison corrections and effect size calculations are needed to more accurately assess an intervention's significance and impact, understanding the limitations of these methods in the case of dependency and correlation is important. In this review, we outline methods for multiple comparison corrections and effect size calculations and considerations in cases of correlation and summarize relevant simulation studies to illustrate these concepts. PMID- 26891393 TI - Net Reclassification Improvement. AB - When adding new markers to existing prediction models, it is necessary to evaluate the models to determine whether the additional markers are useful. The net reclassification improvement (NRI) has gained popularity in this role because of its simplicity, ease of estimation, and understandability. Although the NRI provides a single-number summary describing the improvement new markers bring to a model, it also has several potential disadvantages. Any improved classification by the new model is weighted equally, regardless of the direction of reclassification. In prediction models that already identify the high- and low risk groups well, a positive NRI may not mean better classification of those with medium risk, where it could make the most difference. Also, overfitting, or otherwise misspecified training models, produce overly positive NRI results. Because of the unaccounted for uncertainty in the model coefficient estimation, investigators should rely on bootstrapped confidence intervals rather than on tests of significance. Keeping in mind the limitations and drawbacks, the NRI can be helpful when used correctly. PMID- 26891395 TI - Decreasing the Hours That Anesthesiologists and Nurse Anesthetists Work Late by Making Decisions to Reduce the Hours of Over-Utilized Operating Room Time. AB - In this special article, we evaluate how to reduce the number of hours that anesthesiologists and nurse anesthetists work beyond the end of their scheduled shifts. We limit consideration to surgical suites where the hours of cases in each operating room (OR) average 8 hours or more per day. Let "allocated hours" refer to the hours into which cases are scheduled, calculated months in advance for each combination of service and day of the week. Over-Utilized time is the OR workload exceeding allocated time. Reducing Over-Utilized time is the key to reducing the hours that anesthesia providers work late. Certain decisions that reduce Over-Utilized time and reduce the hours that anesthesiologists and nurse anesthetists work late are made by the surgical committee or perioperative medical director months in advance. Such decisions include increasing the number of first case starts and planning staffing for turnovers and lunch breaks during the busiest times of the day. However, most decisions substantively influencing Over-Utilized OR time are made within 1 workday before the day of surgery and on the day of surgery, because only then are ORs sufficiently full that changes can be made to minimize Over-Utilized time. Decisions to reduce Over-Utilized time on the day of surgery include targeting ORs with expected Over-Utilized time and taking steps to reduce it, including making effective staff assignments and appropriately scheduling add-on cases. PMID- 26891396 TI - Intravenous Therapies for Complex Regional Pain Syndrome: A Systematic Review. AB - Complex regional pain syndrome (CRPS) remains a challenging clinical pain condition. Multidisciplinary approaches have been advocated for managing CRPS. Compared with spinal cord stimulation and intrathecal targeted therapy, IV treatments are less invasive and less costly. We aimed to systemically review the literature on IV therapies and determine the level of evidence to guide the management of CRPS. We searched PubMed, Embase, Scopus, and the Cochrane databases for articles published on IV therapies of CRPS up through February 2015. The search yielded 299 articles, of which 101 were deemed relevant by reading the titles and 63 by reading abstracts. All these 63 articles were retrieved for analysis and discussion. We evaluated the relevant studies and provided recommendations according to the level of evidence. We conclude that there is evidence to support the use of IV bisphosphonates, immunoglobulin, ketamine, or lidocaine as valuable interventions in selected patients with CRPS. However, high-quality studies are required to further evaluate the safety, efficacy, and cost-effectiveness of IV therapies for CRPS. PMID- 26891397 TI - Transforaminal Epidural Steroid Injections for Treating Lumbosacral Radicular Pain from Herniated Intervertebral Discs: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Steroids often are administered into the epidural space through the transforaminal epidural (TFE) route to treat lumbosacral radicular pain secondary to herniated intervertebral discs. However, their efficacy and safety compared with transforaminal epidural local anesthetics (LAs) or saline injections is unclear. METHODS: We reviewed randomized controlled trials that compared TFE injections of steroids (with or without LA) with LA or saline in adult outpatients with lumbosacral radicular pain secondary to herniated intervertebral disks. Databases searched included MEDLINE, EMBASE, Cochrane central register of controlled trials, Cochrane database of systematic reviews, and Google Scholar up to February 2015. Data on scores of numerical rating scale for pain, validated scores for measuring physical disability and quality of life, and incidence of surgery measured at 1 month to 2 years after the interventions were meta analyzed. Strength of evidence was classified with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Eight randomized controlled trials including 771 patients (366 in steroid and 405 in comparator groups) were included. There was variability in the studies in the dose of TFE steroids, frequency, and number of procedures. Patients who received TFE steroids reported a significant, but clinically modest, reduction in mean pain scores (0 10 scale) compared with LA/saline (-0.97 points; 95% confidence interval, -1.42 to -0.51 points; P < 0.0001, I2 = 90%; GRADE weak recommendation; moderate quality evidence) at 3 months after the interventions. TFE steroids did not decrease physical disability at 1 to 3 months after the intervention (GRADE strong recommendation ?; high-quality evidence) or incidence of surgery at 12 months after the intervention (GRADE strong recommendation ?; moderate-quality evidence) compared with LA/saline. CONCLUSIONS: TFE steroids provide modest analgesic benefit at 3 months in patients with lumbosacral radicular pain secondary to herniated intervertebral disks, but they have no impact on physical disability or incidence of surgery. There was a high degree of heterogeneity among the publications included in this meta-analysis. Well-designed, large, randomized studies are required to evaluate appropriate dosages, adverse effects, number of procedures, and the effect of this intervention on psychological disability and quality of life. PMID- 26891398 TI - Human Lumbar Ligamentum Flavum Anatomy for Epidural Anesthesia: Reviewing a 3D MR Based Interactive Model and Postmortem Samples. AB - The ligamentum flavum (LF) forms the anatomic basis for the loss-of-resistance technique essential to the performance of epidural anesthesia. However, the LF presents considerable interindividual variability, including the possibility of midline gaps, which may influence the performance of epidural anesthesia. We devise a method to reconstruct the anatomy of the digitally LF based on magnetic resonance images to clarify the exact limits and edges of LF and its different thickness, depending on the area examined, while avoiding destructive methods, as well as the dissection processes. Anatomic cadaveric cross sections enabled us to visually check the definition of the edges along the entire LF and compare them using 3D image reconstruction methods. Reconstruction was performed in images obtained from 7 patients. Images from 1 patient were used as a basis for the 3D spinal anatomy tool. In parallel, axial cuts, 2 to 3 cm thick, were performed in lumbar spines of 4 frozen cadavers. This technique allowed us to identify the entire ligament and its exact limits, while avoiding alterations resulting from cutting processes or from preparation methods. The LF extended between the laminas of adjacent vertebrae at all vertebral levels of the patients examined, but midline gaps are regularly encountered. These anatomical variants were reproduced in a 3D portable document format. The major anatomical features of the LF were reproduced in the 3D model. Details of its structure and variations of thickness in successive sagittal and axial slides could be visualized. Gaps within LF previously studied in cadavers have been identified in our interactive 3D model, which may help to understand their nature, as well as possible implications for epidural techniques. PMID- 26891399 TI - Opioids and Sleep Apnea: More Than Perioperative Impact. PMID- 26891400 TI - In Response. PMID- 26891401 TI - Association of Sodium Homeostasis with Blood Transfusions During Liver Transplantation. PMID- 26891402 TI - In Response. PMID- 26891403 TI - Ketamine and Mitochondrial Function. PMID- 26891404 TI - In Response. PMID- 26891405 TI - Can We Claim Accuracy from a Regional Near-Infrared Spectroscopy Oximeter? PMID- 26891406 TI - In Response. PMID- 26891407 TI - Dangerous Regulations for a Level 1 Trauma Operating Room. PMID- 26891408 TI - Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study. AB - Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2 nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated in vitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated in vitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers. PMID- 26891409 TI - Update on current evaluation and management of pediatric nasal dermoid. AB - OBJECTIVES/HYPOTHESIS: To review the presentation of congenital pediatric nasal dermoid and present guidelines for its evaluation and management. STUDY DESIGN: Retrospective chart review from 1970 to 2014 at a tertiary referral children's hospital. METHODS: The medical records of all patients diagnosed with a nasal dermoid during the study period were reviewed for demographics, lesion characteristics, imaging, operative details, and outcomes. RESULTS: Ninety-six patients underwent excision of a congenital nasal dermoid during the study period. The mean age at presentation was 3.1 years (range, 0.1-19.3 years). Thirty-four (35%) females and 62 (65%) males were included. The most common presentation was a nasal dorsal mass in 66 (69%) patients. Ninety-two (96%) of the patients underwent preoperative imaging. Seventy-eight (82%) of the patients did not show any clinical or radiographic evidence of intracranial extension preoperatively. Eighty-five (89%) of the patients underwent extracranial excision, and 11 (11%) underwent combined intracranial and extracranial excision. Eight patients (8%) presented with recurrence, on average 3.3 years (range, 1-6 years) after initial excision. Mean follow-up time was 8 years (range, 1-18 years). CONCLUSION: Preoperative imaging of nasal dermoid is crucial to evaluate for intracranial extension, thus facilitating complete removal. Thin section, high-resolution magnetic resonance with contrast provides excellent detail of the extent of the nasal dermoid including intracranial extension. Thin-section high resolution computed tomography with multiplanar reformatted images provides complimentary information regarding the bone anatomy of the frontonasal region. Surgical strategy is dictated by preoperative imaging and is dependent on the extent of the lesion, but limited facial incisions are preferred. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2151-2160, 2016. PMID- 26891410 TI - Soft implantable microelectrodes for future medicine: prosthetics, neural signal recording and neuromodulation. AB - Implantable devices have provided various potential diagnostic options and therapeutic methods in diverse medical fields. A variety of hard-material-based implantable electrodes have been developed. However, several limitations for their chronic implantation remain, including mechanical mismatches at the interface between the electrode and the soft tissue, and biocompatibility. Soft material-based implantable devices are suitable candidates for complementing the limitations of hard electrodes. Advances in microtechnology and materials science have largely solved many challenges, such as optimization of shape, minimization of infection, enhancement of biocompatibility and integration with components for diverse functions. Significant strides have also been made in mechanical matching of electrodes to soft tissue. In this review, we provide an overview of recent advances in soft-material-based implantable electrodes for medical applications, categorized according to their implantation site and material composition. We then review specific applications in three categories: neuroprosthetics, neural signal recording, and neuromodulation. Finally, we describe various strategies for the future development and application of implantable, soft-material-based devices. PMID- 26891411 TI - Smooth muscle and neural dysfunction contribute to different phases of murine postoperative ileus. AB - BACKGROUND: Postoperative ileus (POI) is characterized by a transient inhibition of gastrointestinal (GI) motility after abdominal surgery mediated by the inflammation of the muscularis externa (ME). The aim of this study was to identify alterations in the enteric nervous system that may contribute to the pathogenesis of POI. METHODS: Gastrointestinal transit, contractility of isolated smooth muscle strips and inflammatory parameters were evaluated at different time points (1.5 h to 10 days) after intestinal manipulation (IM) in mice. Immune labeling was used to visualize changes in myenteric neurons. KEY RESULTS: Intestinal manipulation resulted in an immediate inhibition of GI transit recovering between 24 h and 5 days. In vitro contractility to K(+) (60 mM) or carbachol (10(-9) to 10(-4) M) was biphasically suppressed over 24 h after IM (with transient recovery at 6 h). The first phase of impaired myogenic contractility was associated with increased expression of TNF-alpha, IL-6 and IL 1alpha. After 24 h, we identified a significant reduction in electrical field stimulation-evoked contractions and relaxations, lasting up to 10 days after IM. This was associated with a reduced expression of chat and nos1 genes. CONCLUSIONS & INFERENCES: Intestinal manipulation induces two waves of smooth muscle inhibition, most likely mediated by inflammatory cytokines, lasting up to 3 days after IM. Further, we here identify a late third phase (>24 h) characterized by impaired cholinergic and nitrergic neurotransmission persisting after recovery of muscle contractility. These findings illustrate that POI results from inflammation-mediated impaired smooth muscle contraction, but also involves a long-lasting impact of IM on the enteric nervous system. PMID- 26891412 TI - Risk-Adapted Therapy in Early-Stage Chronic Lymphocytic Leukemia. AB - Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and usually affects the elderly patient. More than 50% of CLL cases are diagnosed at an early disease stage, often as an incidental lymphocytosis found in a routine blood screen. For about 40 years, the classifications according to Binet or Rai have been the hands-on staging systems to stratify patients in daily clinical practice. An increasing molecular understanding of the disease and the identification of strong prognostic markers, such as genetic lesions in TP53, have urged clinical scientists to create new scoring systems that improve prognostic risk assessment and treatment allocation. Until today, studies on early treatment interventions in asymptomatic patients using single chemo- or combined chemoimmunotherapy have failed to demonstrate a survival benefit. However, improved risk stratification tools integrating molecular disease features and the availability of new targeted drugs with attractive efficacy and limited toxicity might open new possibilities to re-investigate early treatment in well-defined clinical settings in the future. PMID- 26891413 TI - Genetically Modified Foods: A Brief Overview of the Risk Assessment Process. AB - Billions of people worldwide are unable to meet their daily micro nutritional needs. Genetically modified (GM) foods, while initially developed to tolerate herbicides and resist disease and insects, have the potential to help alleviate this issue that is currently posing a serious public health concern. However, there is a negative public perception surrounding GM foods, calling for more research regarding the risks that GM foods could pose to the public, specifically on the topics of allergenicity and gene transfer. The risk assessments of GM foods should be performed on a case-by-case basis, by a process outlined by the WHO. The goal of determining food safety is to obtain reasonable certainty that under normal levels of consumption, there will be no harm to people. Current research has shown that GM foods do not cause increased allergenicity or have a meaningful risk of gene transfer to people. GM foods should become publicly accepted products that can bring significant benefit to people at risk of under nutrition. PMID- 26891414 TI - Quadrupole interactions: NMR, NQR, and in between from a single viewpoint. AB - Nuclear spins with quantum numbers >1/2 can interact with a static magnetic field, or a local electric field gradient, to produce quantized energy levels. If the magnetic field interaction dominates, we are doing nuclear magnetic resonance (NMR). If the interaction of the nuclear electric quadrupole with electric field gradients is much stronger, this is nuclear quadrupole resonance (NQR). The two are extremes of a continuum, as the ratio of one interaction to the other changes. In this work, we look at this continuum from a single, unified viewpoint based on a Liouville-space approach: the direct method. This method does not require explicit operators and their commutators, unlike Hamiltonian methods. We derive both the quadrupole-perturbed NMR solution and also the Zeeman-perturbed NQR results. Furthermore, we examine the polarization of these signals, because this is different between pure NMR and pure NQR spectroscopy. Spin 3/2 is the focus here, but the approach is perfectly general and can be applied to any spin. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891416 TI - Evidence level. PMID- 26891415 TI - Biochemical analysis of the living human vitreous. AB - BACKGROUND: To date, our understanding of the biochemical composition of the living human vitreous relies on extrapolations from animal or human post-mortem studies. METHODS: This was a cross-sectional study of vitreous samples from 27 individuals scheduled for retinal surgery within a tertiary hospital. From each vitreous sample, the concentrations of sodium, potassium, chloride, calcium, magnesium, glucose, lactate, beta- hydroxybutyrate, copper, zinc, selenium, iron, ferritin and transferrin and osmolality were measured. Perioperative serum samples were also obtained for comparison. RESULTS: The following vitreous mean +/- standard deviation (95% confidence interval of the mean) was observed for each analyte: sodium, 146.7 +/- 3.3 (145.4-148.0) mmol/L; potassium, 5.73 +/- 0.86 (5.39-6.08) mmol/L; chloride, 121.6 +/- 2.6 (120.6-122.7) mmol/L; calcium, 1.128 +/- 0.518 (0.923-1.333) mmol/L; magnesium, 0.900 +/- 0.158 (0.838-0.962) mmol/L; glucose, 2.97 +/- 0.98 (2.58-3.36) mmol/L; lactate, 3.97 +/- 1.09 (3.54 4.40) mmol/L; osmolality, 289.5 +/- 6.9 (286.6-292.5) mOsm/kg; BOHB, 0.0937 +/- 0.0472 (0.0750-0.1124) mmol/L; copper, 0.519 +/- 0.269 (0.412-0.625) umol/L; zinc, 1.95 +/- 1.09 (1.52-2.38) umol/L; selenium, 0.1035 +/- 0.0276 (0.0923 0.1146) umol/L; iron, 3.11 +/- 1.40 (2.56-3.66) umol/L; ferritin, 19.5 +/- 10.3 (15.5-23.6) ug/L; transferrin, 0.0878 +/- 0.0526 (0.0670-0.1086) g/L. Vitreous biochemistry was not significantly different between male and female participants. Vitreous biochemistry was significantly different between non diabetic and diabetic participants. Vitreous biochemistry was significantly different from the vitreous substitute BSS Plus (Alcon, USA). The vitreous extracted from living humans was markedly different from the commonly reported reference values obtained from animal studies. CONCLUSIONS: The current data provide hitherto unavailable information about the biochemical composition of the living human vitreous. PMID- 26891417 TI - Association of thiol disulfide homeostasis with slow coronary flow. AB - Objective The aim of this study was to investigate the role of thiol disulfide homeostasis in the presence of slow coronary flow. Material and methods In this cross-sectional study, a total of 110 patients who admitted to our hospital between March 2014 and December 2015 were included in the study. There were 65 patients in the slow coronary flow, and 45 patients in the normal flow groups. Results We found significant differences between slow coronary flow and the normal flow groups for thiol disulfide homeostasis, and the results of our study indicated that hsCRP, and thiol disulfide ratio were independently associated with slow coronary flow. Conclusion Our study showed that thiol disulfide homeostasis was significantly and independently related to the presence of slow coronary flow. PMID- 26891419 TI - Effect of Structural Modifications on the Self-Assembly of Oligoprolines Conjugated with Sterically Demanding Chromophores. AB - Conjugates between oligoprolines and sterically demanding perylene monoimides (PMIs) form hierarchical supramolecular self-assemblies. The influence of the length and stereochemistry at the attachment site between the peptide backbone and the chromophore on the self-assembly properties of the conjugates was explored. Comparison between oligoprolines bearing 4R- or 4S-configured azidoprolines (Azp) for the conjugation with the PMIs revealed that diastereoisomers with 4R configuration guide the self-assembly consistently better than conjugates with 4S configuration. Elongating the peptide chain beyond nine proline residues or introducing structural "errors", by altering the absolute configuration of one stereogenic center at the outside of the functionalizable oligoproline helix, lowered the efficacy of self-assembly significantly, both in solution phase and in the solid state. The results showed how subtle structural modifications allow for tuning the self-assembly of chromophores and provided further design principles for the development of peptide-chromophore conjugates into nanostructured materials. PMID- 26891418 TI - On-treatment HCV RNA in patients with varying degrees of fibrosis and cirrhosis in the SOLAR-1 trial. AB - BACKGROUND: In the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease. METHODS: We performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS(r) Ampliprep(r)/Cobas TaqMan HCV Test, Version 2.0 with a lower limit of quantification (LLOQ) of 15 IU/ml. RESULTS: Most patients achieved HCV RNA 60%, and selection of embryo-fetal cells was achieved by micromanipulation. In all 302 cases, there was concordance between DNA obtained from celomic fluid samples and fetal or newborn DNA. CONCLUSIONS: Celocentesis can be a reliable procedure for earlier prenatal diagnosis of fetal monogenic diseases. PMID- 26891447 TI - Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications. AB - Reactive oxygen species (ROS) play important roles in cell signaling pathways, while increased production of ROS may disrupt cellular homeostasis, giving rise to oxidative stress and a series of diseases. Utilizing these cell-generated species as triggers for selective tuning polymer structures and properties represents a promising methodology for disease diagnosis and treatment. Recently, significant progress has been made in fabricating biomaterials including nanoparticles and macroscopic networks to interact with this dynamic physiological condition. These ROS-responsive platforms have shown potential in a range of biomedical applications, such as cancer targeted drug delivery systems, cell therapy platforms for inflammation related disease, and so on. PMID- 26891449 TI - Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study. AB - OBJECTIVE: High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. METHODS AND RESULTS: Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmo Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. CONCLUSIONS: Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded. PMID- 26891448 TI - Transcriptome-Wide Analysis of Hepatitis B Virus-Mediated Changes to Normal Hepatocyte Gene Expression. AB - Globally, a chronic hepatitis B virus (HBV) infection remains the leading cause of primary liver cancer. The mechanisms leading to the development of HBV associated liver cancer remain incompletely understood. In part, this is because studies have been limited by the lack of effective model systems that are both readily available and mimic the cellular environment of a normal hepatocyte. Additionally, many studies have focused on single, specific factors or pathways that may be affected by HBV, without addressing cell physiology as a whole. Here, we apply RNA-seq technology to investigate transcriptome-wide, HBV-mediated changes in gene expression to identify single factors and pathways as well as networks of genes and pathways that are affected in the context of HBV replication. Importantly, these studies were conducted in an ex vivo model of cultured primary hepatocytes, allowing for the transcriptomic characterization of this model system and an investigation of early HBV-mediated effects in a biologically relevant context. We analyzed differential gene expression within the context of time-mediated gene-expression changes and show that in the context of HBV replication a number of genes and cellular pathways are altered, including those associated with metabolism, cell cycle regulation, and lipid biosynthesis. Multiple analysis pipelines, as well as qRT-PCR and an independent, replicate RNA seq analysis, were used to identify and confirm differentially expressed genes. HBV-mediated alterations to the transcriptome that we identified likely represent early changes to hepatocytes following an HBV infection, suggesting potential targets for early therapeutic intervention. Overall, these studies have produced a valuable resource that can be used to expand our understanding of the complex network of host-virus interactions and the impact of HBV-mediated changes to normal hepatocyte physiology on viral replication. PMID- 26891450 TI - Transcriptome Analysis and Discovery of Genes Relevant to Development in Bradysia odoriphaga at Three Developmental Stages. AB - Bradysia odoriphaga (Diptera: Sciaridae) is the most important pest of Chinese chive (Allium tuberosum) in Asia; however, the molecular genetics are poorly understood. To explore the molecular biological mechanism of development, Illumina sequencing and de novo assembly were performed in the third-instar, fourth-instar, and pupal B. odoriphaga. The study resulted in 16.2 Gb of clean data and 47,578 unigenes (>=125 bp) contained in 7,632,430 contigs, 46.21% of which were annotated from non-redundant protein (NR), Gene Ontology (GO), Clusters of Orthologous Groups (COG), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. It was found that 19.67% of unigenes matched the homologous species mainly, including Aedes aegypti, Culex quinquefasciatus, Ceratitis capitata, and Anopheles gambiae. According to differentially expressed gene (DEG) analysis, 143, 490, and 309 DEGs were annotated as involved in the developmental process in the GO database respectively, in the comparisons of third-instar and fourth-instar larvae, third instar larvae and pupae, and fourth-instar larvae and pupae. Twenty-five genes were closely related to these processes, including developmental process, reproduction process, and reproductive organs development and programmed cell death (PCD). The information of unigenes assembled in B. odoriphaga through transcriptome and DEG analyses could provide a detailed genetic basis and regulated information for elaborating the developmental mechanism from the larval, pre-pupal to pupal stages of B. odoriphaga. PMID- 26891451 TI - Puerarin for ischaemic stroke. AB - BACKGROUND: Puerarin, a form of herbal medicine, is widely used in the treatment of ischaemic stroke in China. OBJECTIVES: To assess the effects of puerarin in people with ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register and the Chinese Stroke Trials Register (last searched August 2015). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 7), MEDLINE (1948 to August 2015), EMBASE (1980 to August 2015), AMED (the Allied and Complementary Medicine Database, 1985 to August 2015) and the China Biological Medicine Database (CBM disc 1979 to August 2015). We searched reference lists, relevant clinical trials and research registers and contacted pharmaceutical companies and researchers in an effort to identify further published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled clinical trials comparing puerarin with placebo or open control (no placebo) in people with ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, assessed trial quality and risk of bias, and extracted the data. MAIN RESULTS: We included 20 RCTs with 1574 participants in this updated review. All trials were published in Chinese language journals. We included 14 trials that we had excluded in the previous version of the review after we added a new outcome in this update. Time windows within which the participants were randomised ranged from 4.5 hours to 10 days. Ischaemic stroke was confirmed by computerised tomography (CT) or magnetic resonance imaging (MRI) in 18 trials. Meta-analysis of two trials with 164 participants showed that treatment with puerarin did not reduce death or dependency at final follow-up (RR 0.79, 95% CI 0.45 to 1.36). One trial with 83 participants reported that the mean value of the Barthel Index in the puerarin group was below that in the control group. Meta-analysis of 16 trials with 1305 participants showed that puerarin reduced the proportion of participants without improvement of neurological deficit at the end of follow-up (RR 0.42, 95% CI 0.33 to 0.55). None of the included trials reported serious adverse effects.The quality of evidence was low due to incomplete reporting of the methods and short term follow-up. AUTHORS' CONCLUSIONS: There is not enough evidence to evaluate the effect of puerarin on survival or dependency in people with ischaemic stroke. High quality and large-scale RCTs with long-term follow-up are needed to assess its efficacy. PMID- 26891453 TI - Effect of Stabilization on the Healing Process of Femur Fractures in Aged Mice. AB - BACKGROUND: The influence of mechanical stability on fracture healing has previously been studied in adult mice, but is poorly understood in aged animals. Therefore, we herein studied the effect of stabilization on the healing process of femur fractures in aged mice. METHODS: Twenty-four 18-month-old CD-1 mice were stabilized after midshaft fracture of the femur with an intramedullary screw. In another 24 18-month-old mice, the femur fractures were left unstabilized. Bone healing was studied by radiological, biomechanical, histomorphometric, and protein expression analyses. RESULTS: After 2 and 5 weeks of healing, the callus of nonstabilized fractures compared to stabilized fractures was significantly larger, containing a significantly smaller amount of osseous tissue and a higher amount of cartilaginous tissue. This was associated with a significantly lower biomechanical stiffness during the early phase of healing. However, during the late phase of fracture healing both nonstabilized and stabilized fractures showed a biomechanical stiffness of ~40%. Of interest, Western blot analyses of callus tissue demonstrated that the expression of proteins related to angiogenesis, bone formation and remodeling, i.e. VEGF, CYR61, BMP-2, BMP-4, Col-2, Col-10, RANKL, OPG, did not differ between nonstabilized and stabilized fractures. CONCLUSION: Nonstabilized fractures in aged mice show delayed healing and remodeling. This is not caused by an altered protein expression in the callus but rather by the excessive interfragmentary movements. PMID- 26891452 TI - Dynamic Imaging of Individual Remyelination Profiles in Multiple Sclerosis. AB - BACKGROUND: Quantitative in vivo imaging of myelin loss and repair in patients with multiple sclerosis (MS) is essential to understand the pathogenesis of the disease and to evaluate promyelinating therapies. Selectively binding myelin in the central nervous system white matter, Pittsburgh compound B ([11 C]PiB) can be used as a positron emission tomography (PET) tracer to explore myelin dynamics in MS. METHODS: Patients with active relapsing-remitting MS (n = 20) and healthy controls (n = 8) were included in a longitudinal trial combining PET with [11 C]PiB and magnetic resonance imaging. Voxel-wise maps of [11 C]PiB distribution volume ratio, reflecting myelin content, were derived. Three dynamic indices were calculated for each patient: the global index of myelin content change; the index of demyelination; and the index of remyelination. RESULTS: At baseline, there was a progressive reduction in [11 C]PiB binding from the normal-appearing white matter to MS lesions, reflecting a decline in myelin content. White matter lesions were characterized by a centripetal decrease in the tracer binding at the voxel level. During follow-up, high between-patient variability was found for all indices of myelin content change. Dynamic remyelination was inversely correlated with clinical disability (p = 0.006 and beta-coefficient = -0.67 with the Expanded Disability Status Scale; p = 0.003 and beta-coefficient = -0.68 with the MS Severity Scale), whereas no significant clinical correlation was found for the demyelination index. INTERPRETATION: [11 C]PiB PET allows quantification of myelin dynamics in MS and enables stratification of patients depending on their individual remyelination potential, which significantly correlates with clinical disability. This technique should be considered to assess novel promyelinating drugs. Ann Neurol 2016;79:726-738. PMID- 26891454 TI - Functional significance of transgelin-2 in uterine cervical squamous cell carcinoma. AB - AIM: Transgelin-2 (TAGLN2) has previously been found to be highly expressed in uterine cervical squamous cell carcinoma (SCC) tissues by proteomic analyses. The present study investigated the role of TAGLN2 in the malignant behaviors of cervical SCC cells in vitro and in vivo, and the clinical significance of TAGLN2 using immunohistochemistry for human cervical SCC tissues. METHODS: Antisense (AS) constructs of TAGLN2 cDNA (AS clones) and the empty vector (control clone) were transfected into a human uterine SCC cell line (SKG IIIa), and malignant behaviors were analyzed in vitro. In an in vivo experiment, 10(7) cells of the AS and control clones were subcutaneously inoculated into female BALB/c nude mice. In immunohistochemistry with anti-TAGLN2 antibodies for human cervical SCC, FIGO stage IA and IB (n = 75), the expression patterns of TAGLN2 were divided into two groups: weak and strong. The relation between expression pattern and prognosis was analyzed. RESULTS: Suppression of TAGLN2 inhibited cancer cell migration and secretion of matrix metalloproteinases. Tumors in the control clone group continued to grow, whereas those in the AS clone group clearly stopped growing. Six weeks after injection, the tumor size was significantly smaller in the AS clone group than in the control clone group. Immunohistochemistry revealed that the strong pattern was associated with poor overall survival compared with the weak pattern by the Kaplan-Meier method. CONCLUSION: TAGLN2 plays functional roles in the progression of cervical SCC. Suppression of TAGLN2 may be a new strategy for the treatment of cervical SCC. PMID- 26891455 TI - Mesenchymal Stem Cells Induce Suppressive Macrophages Through Phagocytosis in a Mouse Model of Asthma. AB - Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti-inflammatory therapy in allergic asthma. However, the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)-induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and decreased ex vivo carbachol-induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To evaluate in vivo MSC survival, MSCs were labeled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digested to obtain single-cell suspensions. 91.5 +/- 2.3% and 86.6 +/- 6.3% of the recovered PKH26(+) lung cells expressed specific macrophage markers in control and Der f mice, respectively, suggesting that macrophages had phagocyted in vivo the injected MSCs. Interestingly, only PKH26(+) macrophages expressed M2 phenotype, while the innate PKH26(-) macrophages expressed M1 phenotype. Finally, the remaining 0.5% PKH26(+) MSCs expressed 10- to 100-fold more COX-2 than before injection, suggesting in vivo MSC phenotype modification. Together, the results of this study indicate that MSCs attenuate asthma by being phagocyted by lung macrophages, which in turn acquire a M2 suppressive phenotype. Stem Cells 2016;34:1836-1845. PMID- 26891456 TI - In Situ Synthesis of Antimicrobial Silver Nanoparticles within Antifouling Zwitterionic Hydrogels by Catecholic Redox Chemistry for Wound Healing Application. AB - A multifunctional hydrogel that combines the dual functionality of both antifouling and antimicrobial capacities holds great potential for many bioapplications. Many approaches and different materials have been employed to synthesize such a material. However, a systematic study, including in vitro and in vivo evaluation, on such a material as wound dressings is highly scarce at present. Herein, we report on a new strategy that uses catecholic chemistry to synthesize antimicrobial silver nanoparticles impregnated into antifouling zwitterionic hydrogels. For this purpose, hydrophobic dopamine methacrylamide monomer (DMA) was mixed in an aqueous solution of sodium tetraborate decahydrate and DMA monomer became soluble after increasing pH to 9 due to the complexation between catechol groups and boron. Then, cross-linking polymerization of zwitterionic monomer was carried out with the solution of the protected dopamine monomer to produce a new hydrogel. When this new hydrogel comes in contact with a silver nitrate solution, silver nanoparticles (AgNPs) are formed in its structure as a result of the redox property of the catechol groups and in the absence of any other external reducing agent. The results obtained from TEM and XRD measurements indicate that AgNPs with diameters of around 20 nm had formed within the networks. FESEM images confirmed that the silver nanoparticles were homogeneously incorporated throughout the hydrogel network, and FTIR spectroscopy demonstrated that the catechol moiety in the polymeric backbone of the hydrogel is responsible for the reduction of silver ions into the AgNPs. Finally, the in vitro and in vivo experiments suggest that these mussel-inspired, antifouling, antibacterial hydrogels have great potential for use in wound healing applications. PMID- 26891457 TI - Inhibited attachment behaviour and disinhibited social engagement behaviour as relevant concepts in referred home reared children. AB - BACKGROUND: Disorders of attachment and social engagement have mainly been studied in children, reared in institutions and foster care. There are few studies amongst home reared children living with biological parents. The aim of this study was to test the clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children, referred for treatment of emotional and behavioural problems, compared with young children in treatment foster care. METHODS: The Disturbances of Attachment Interview, Maltreatment Classification System, the Child Behaviour Checklist and Parenting Stress Index were used in 141 referred home reared children and 59 referred foster children, aged 2.0-7.9 years (M = 4.7, SE = 1.3), 71% boys. RESULTS: Inhibited attachment behaviour was less prevalent in the referred home reared group (9%) than in the foster care group (27%). Disinhibited social engagement behaviour was found in 42% of the home reared group, similar to the foster care group. Inhibited attachment behaviour and disinhibited social engagement behaviour were not associated with child maltreatment. More inhibited attachment behaviour was associated with clinical levels of child internalizing and externalizing behaviour in the home reared group, not in the foster care group. In both groups, more disinhibited social engagement behaviour was associated with clinical levels of externalizing behaviour and with more parenting stress. CONCLUSIONS: Even without evident links to maltreatment, results of this study suggest clinical significance of inhibited attachment behaviour and disinhibited social engagement behaviour in young home reared children referred for treatment of emotional and behavioural problems. PMID- 26891458 TI - The impact of comorbidity on cancer and its treatment. AB - Answer questions and earn CME/CNE Comorbidity is common among cancer patients and, with an aging population, is becoming more so. Comorbidity potentially affects the development, stage at diagnosis, treatment, and outcomes of people with cancer. Despite the intimate relationship between comorbidity and cancer, there is limited consensus on how to record, interpret, or manage comorbidity in the context of cancer, with the result that patients who have comorbidity are less likely to receive treatment with curative intent. Evidence in this area is lacking because of the frequent exclusion of patients with comorbidity from randomized controlled trials. There is evidence that some patients with comorbidity have potentially curative treatment unnecessarily modified, compromising optimal care. Patients with comorbidity have poorer survival, poorer quality of life, and higher health care costs. Strategies to address these issues include improving the evidence base for patients with comorbidity, further development of clinical tools to assist decision making, improved integration and coordination of care, and skill development for clinicians. CA Cancer J Clin 2016;66:337-350. (c) 2016 American Cancer Society. PMID- 26891459 TI - Amorphous Ni-B alloy nanoparticle film on Ni foam: rapid alternately dipping deposition for efficient overall water splitting. AB - It is highly attractive, but still remains challenging, to develop noble metal free bifunctional electrocatalysts efficient for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline media. In this letter, we describe the rapid electroless deposition of amorphous Ni-B nanoparticle film on Ni foam (Ni-B/Ni foam) by alternative dipping of Ni foam into Ni precursor and reducing solutions. This Ni-B/Ni foam acts as an efficient and durable 3D catalytic electrode for water splitting, affording 100 mA cm(-2) at 360 mV overpotential for the OER and 20 mA cm(-2) at 125 mV overpotential for the HER in 1.0 M KOH, and its two-electrode electrolyzer demands a cell voltage of 1.69 V to afford 15 mA cm(-2) water-splitting current. Moreover, the catalyst loading can be easily tuned and this alternately dipping deposition technique works universally for other conductive substrates. PMID- 26891460 TI - Spectrum of factor X gene mutations in Iranian patients with congenital factor X deficiency. AB - Congenital factor X deficiency is one of the most severe forms of rare bleeding disorders transmitted in autosomal recessive manner. According to the World Federation of Hemophilia survey, 153 patients with factor X deficiency (FXD) live in Iran, but a few studies have been performed to determine the precise distribution of FXD in different parts of the country and to assess molecular basis of this disorder in Iranian patients. This study was conducted to assess the spectrum of factor X gene mutation in Iranian patients with congenital FXD. All relevant English and Persian-language publications were searched (until 2015). Clinical presentations or molecular basis of nearly 90 Iranian patients were reported in different studies. Most of these studies focused on clinical presentations of patients, whereas molecular analyses were rarely performed. Most molecular studies found a diversity in factor X disease causing mutations in Iranian patients. Like other parts of the world, the majority of mutations in Iranian patients were missense mutations, but splice-site mutations were relatively common. Three extremely rare cases of combined factor X and factor VII deficiencies were observed in two cases of which this disorder resulted from different missense mutations in respective factor genes. A wide spectrum of factor X gene mutations was observed in Iranian patients with congenital FXD that revealed diversity in FXD gene mutations. PMID- 26891461 TI - Small-Molecule CD4 Mimics Containing Mono-cyclohexyl Moieties as HIV Entry Inhibitors. AB - CD4 mimics are small molecules that inhibit the protein-protein interaction between gp120 and CD4, which is a key interaction for the entry of human immunodeficiency virus (HIV) into host immune cells. In the present study, mono cyclohexyl-type CD4 mimics were designed to form hydrophobic and electrostatic interactions with Val430 and Asp368 located in the entrance of the Phe43 cavity of gp120, the interaction site of CD4. YIR-329, a novel 1-azaspiro[5.5]undecane derivative with a cyclohexyl ring attached to the piperidine ring, exhibited only slightly weaker anti-HIV activity than a previously described lead HAR-171, and modeling results indicated the formation of advantageous interactions by the para chlorophenyl moiety of YIR-329. To introduce an electrostatic interaction with Asp368, derivatives with a guanidino group on the piperidine nitrogen atom were synthesized. Mono-cyclohexyl-type CD4 mimics with a guanidino group, such as YIR 819 (N(1) -(4-chlorophenyl)-N(2) -(1-(2-(N-(amidino)glycinamide)ethyl)-2 cyclohexylpiperidin-4-yl)oxalamide) and YIR-821 (1-(2-(5 guanidinovaleramide)ethyl derivative of YIR-819), were identified that exhibit approximately fivefold more potent anti-HIV activity than YIR-329. In combination with a neutralizing antibody, their anti-HIV activities were augmenting. Modeling results suggest that these compounds interact effectively with Val430 and either Asp368 or Asp474 in the gp120 Phe43 cavity. YIR-819 and YIR-821 represent useful lead compounds for the further development of HIV-1 entry inhibitors and could potentially be useful for co-administration with neutralizing antibodies for the treatment of HIV infection and AIDS. PMID- 26891462 TI - Neurite outgrowth enhancement by jiadifenolide: possible targets. AB - Covering: 1860-2016A mechanistic link may exist between convulsant plant substances typified by picrotoxinin, and 'neurotrophic' sesquiterpenes like jiadifenolide. Picrotoxinin elicits convulsion by anion blockade of the Cys-loop family of neurotransmitter-gated ion channels. These same receptors mediate neuronal development and neurite outgrowth prior to synapse formation. Due to its structural homology with picrotoxin and anisatin, it is possible that jiadifenolide enhances NGF-stimulated neurite outgrowth by modulation of the Cys loop family of receptors. PMID- 26891464 TI - Objective and subjective measures of cross-situational learning. AB - Statistical learning is often considered to be automatic and implicit, but little is known about the extent to which the resulting representations are available to conscious awareness. In the present study, we focus on whether the knowledge acquired in statistical learning of word-referent pairs is available to conscious control. Using a cross-situational learning paradigm, adult participants were first exposed to a set of pictures associated with auditorily presented words. Immediately thereafter, they were exposed to a second set of word-picture pairs. After the exposure phase, learning and conscious accessibility to the acquired knowledge were measured by using an adaptation of the Process Dissociation Procedure (Jacoby, 1991): two recognition tasks that only differed by instructions. In the Inclusion task, participants were instructed to accept all the correct associations (either from the first or the second set) and reject all the incorrect associations. In the Exclusion task, they had to accept all the correct associations from one of the sets and reject both the correct associations from the other set as well as all incorrect associations. Moreover, binary confidence judgments were recorded after each trial. Results show that participants were able to control the acquired knowledge. However, confidence judgments revealed that participants correctly identified the learned associations even when they claimed to guess, suggesting that cross-situational learning involves a mixture of both conscious and unconscious influences. PMID- 26891463 TI - The contribution of caregiver psychosocial factors to distress associated with behavioural and psychological symptoms in dementia. AB - OBJECTIVE: The objective of the study is to examine caregiver factors as predictors of BPSD-related distress and their potential mechanisms. METHOD: Informal caregivers of people with dementia (n = 157) recruited from 28 community mental health teams in six NHS Trusts across England completed questionnaires regarding psychosocial factors (relationship quality, competence, guilt, health related quality of life in the caregiver and person with dementia, reactivity to behavioural and psychological symptoms in dementia [BPSD] and burden) and frequency of BPSD. Analyses of BPSD-related distress include hierarchical multiple regression, mediation, moderation and path analysis. RESULTS: Caregiver psychosocial factors explained 56% of the variance in BPSD-related distress. After controlling for these factors, frequency of BPSD was not a significant predictor of BPSD-related distress. Caregiver reactivity to BPSD, burden, competence and relationship quality directly influenced BPSD-related distress. Guilt influenced distress indirectly via competence, burden and reactivity to BPSD. The final model accounted for 41% of the variance in BPSD-related distress and achieved a good fit to the data (chi2 = 23.920, df = 19, p = 0.199). CONCLUSIONS: Caregiver psychosocial factors including sense of competence, guilt, burden and reactivity to BPSD contribute to BPSD-related distress. Tailored interventions for managing behaviour problems in family settings could focus on these factors associated with BPSD-related distress to minimise distress in families. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891465 TI - Observed activation status of lane departure warning and forward collision warning of Honda vehicles at dealership service centers. AB - OBJECTIVE: There are little objective data on whether drivers with lane departure warning and forward collision warning systems actually use them, but self-report data indicate that lane departure warning may be used less and viewed less favorably than forward collision warning. The current study assessed whether the systems were turned on when drivers brought their vehicles to dealership service stations and whether the observational protocol is a feasible method for collecting similar data on various manufacturers' systems. METHODS: Observations of 2013-2015 Honda Accords, 2014-2015 Odysseys, and 2015 CR-Vs occurred at 2 U.S. Honda dealerships for approximately 4 weeks during Summer 2015. RESULTS: Of the 265 vehicles observed to have the 2 systems, 87 (32.8%) had lane departure warning turned on. Accords were associated with a 66% increase in the likelihood that lane departure warning was turned on compared with Odysseys, but the rate was still only about 40% in Accords. In contrast, forward collision warning was turned on in all but one of the observed vehicles. CONCLUSIONS: Observations found that the activation rate was much higher for forward collision warning than lane departure warning. The observation method worked well and appears feasible for extending to other manufacturers. PMID- 26891466 TI - Shen's Whole-Layer Tightly Appressed Anastomosis Technique for Duct-to-Mucosa Pancreaticojejunostomy in Pancreaticoduodenectomy. AB - BACKGROUND Postoperative pancreatic fistulas (POPFs) due to anastomotic leaks are always closely related to significant morbidity and mortality following pancreaticoduodenectomy (PD). A series of modified anastomotic methods have been proposed. The object of our study was to provide a novel anastomotic method for operations involving the Child technique, termed the "whole-layer tightly appressed anastomosis technique". MATERIAL AND METHODS An improved pancreatic whole-layer suture technique was used when we performed the duct-to-mucosa pancreaticojejunostomies; this method ensured the tight joining of the pancreatic stump and jejunum and decreased the pinholes in the pancreatic stump. This new method was used in 41 patients, and was compared with the traditional duct-to mucosa anastomosis technique that was used in 50 patients as controls. RESULTS The POPF rate was much lower in the new method group than in the control group (6, 14.63% and 20, 40.00%, respectively, P=0.010). There were 5 grade A POPF patients and 1 grade B POPF patient in the study group. In the control group there were 12 grade A POPFs patients, 7 grade B POPFs patients, and 1 grade C POPF patient. The study group exhibited a lower morbidity rate (7, 17.07% vs. 16, 32.00%, P=0.022) and a reduced hospital stay (17.16 d vs. 22.92 d, P=0.001). CONCLUSIONS The whole-layer tightly appressed anastomosis technique presented in our study is a safer anastomotic method than the traditional duct-to-mucosa pancreaticojejunostomy technique. This new technique effectively reduced the incidence of POPF after PD and decreased the postoperative morbidity. PMID- 26891467 TI - Docetaxel-based adjuvant therapy for breast cancer patients in Asia-Pacific region: Results from 5 years follow-up on Asia-Pacific Breast Initiative-I. AB - AIM: To acquire patient characteristics, safety, relapse and survival outcomes of early-stage breast cancer patients receiving docetaxel (Taxotere(R))-based regimen in adjuvant setting from the Asia-Pacific region. METHODS: This was an open-label, international, longitudinal, multicenter, observational, prospective cohort of consecutive early breast cancer (EBC) patients with a high risk of recurrence being treated with various docetaxel-containing anthracycline and non anthracycline adjuvant regimens during 2006-2013. RESULTS: In this study, 1542 patients were enrolled. Anthracycline-containing regimens were administered in 92% of patients, while 8% of patients received non-anthracycline-containing docetaxel-based regimens. The mean dose intensity of docetaxel was 25.8, 22.4 and 25.4 mg/m(2) /week among patients receiving docetaxel-based monotherapy, combination and sequential therapy, respectively. Adverse events were reported in 94.9% of patients (anthracycline vs non-anthracycline regimen; 95.1% vs 93.5%). Serious adverse events were reported in 12.6% of patients (12.4% vs 14.6%). Grade 4 neutropenia was reported in 25.2% of patients (24.7% vs 30.9%) and febrile neutropenia in 1.9% of patients (2% vs 0.8%). Only 7% of patients had a relapse or a second primary malignancy. At 5-year follow-up, there were 127 (8.3%) deaths (8.4% vs 6.5%). CONCLUSION: The Asia-Pacific Breast Initiative-I registry highlights the important patient and treatment characteristics of EBC patients treated with adjuvant docetaxel chemotherapy from the Asia-Pacific region that will help physicians to understand the impact of different docetaxel treatments on the clinical outcomes in this population. PMID- 26891469 TI - Buckling prevention strategies in nature as inspiration for improving percutaneous instruments: a review. AB - A typical mechanical failure mode observed in slender percutaneous instruments, such as needles and guidewires, is buckling. Buckling is observed when the axial compressive force that is required to penetrate certain tissue types exceeds the critical load of the instrument and manifests itself by sudden lateral deflection of the instrument. In nature, several organisms are able to penetrate substrates without buckling while using apparatuses with diameters smaller than those of off the-shelf available percutaneous needles and guidewires. In this study we reviewed the apparatuses and buckling prevention strategies employed by biological organisms to penetrate substrates such as wood and skin. A subdivision is made between buckling prevention strategies that focus on increasing the critical load of the penetration tool and strategies that focus on decreasing the penetration load of the substrate. In total, 28 buckling prevention strategies were identified and categorized. Most organisms appear to be using a combination of buckling prevention strategies simultaneously. Integration and combination of these biological buckling prevention strategies in percutaneous instruments may contribute to increasing the success rate of percutaneous interventions. PMID- 26891468 TI - Pulsed electromagnetic fields promote in vitro osteoblastogenesis through a Wnt/beta-catenin signaling-associated mechanism. AB - Substantial evidence indicates that pulsed electromagnetic fields (PEMF) could accelerate fracture healing and enhance bone mass, whereas the unclear mechanism by which PEMF stimulation promotes osteogenesis limits its extensive clinical application. In the present study, effects and potential molecular signaling mechanisms of PEMF on in vitro osteoblasts were systematically investigated. Osteoblast-like MC3T3-E1 cells were exposed to PEMF burst (0.5, 1, 2, or 6 h/day) with 15.38 Hz at various intensities (5 Gs (0.5 mT), 10 Gs (1 mT), or 20 Gs (2 mT)) for 3 consecutive days. PEMF stimulation at 20 Gs (2 mT) for 2 h/day exhibited most prominent promotive effects on osteoblastic proliferation via Cell Counting kit-8 analyses. PEMF exposure induced well-organized cytoskeleton, and promoted formation of extracellular matrix mineralization nodules. Significantly increased proliferation-related gene expressions at the proliferation phase were observed after PEMF stimulation, including Ccnd 1 and Ccne 1. PEMF resulted in significantly increased gene and protein expressions of alkaline phosphatase and osteocalcin at the differentiation phase of osteoblasts rather than the proliferation phase via quantitative reverse transcription polymerase chain reaction and Western blotting analyses. Moreover, PEMF upregulated gene and protein expressions of collagen type 1, Runt-related transcription factor 2 and Wnt/beta-catenin signaling (Wnt1, Lrp6, and beta-catenin) at proliferation and differentiation phases. Together, our present findings highlight that PEMF stimulated osteoblastic functions through a Wnt/beta-catenin signaling-associated mechanism and, hence, regulates downstream osteogenesis-associated gene/protein expressions. Bioelectromagnetics. 37:152-162, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26891470 TI - Covalent Modification of MoS2 with Poly(N-vinylcarbazole) for Solid-State Broadband Optical Limiters. AB - New soluble MoS2 nanosheets covalently functionalized with poly(N-vinylcarbazole) (MoS2-PVK) were in situ synthesized for the first time. In contrast to MoS2 and MoS2 /PVK blends, both the solution of MoS2 -PVK in DMF and MoS2-PVK/poly(methyl methacrylate) (PMMA) film show superior nonlinear optical and optical limiting responses. The MoS2-PVK/PMMA film shows the largest nonlinear coefficients (betaeff) of about 917 cm GW(-1) at lambda=532 nm (cf. 100.69 cm GW(-1) for MoS2/PMMA and 125.12 cm GW(-1) for MoS2/PVK/PMMA) and about 461 cm GW(-1) at lambda=1064 nm (cf. -48.92 cm GW(-1) for MoS2/PMMA and 147.56 cm GW(-1) for MoS2/PVK/PMMA). A larger optical limiting effect, with thresholds of about 0.3 GW cm(-2) at lambda=532 nm and about 0.5 GW cm(-2) at lambda=1064 nm, was also achieved from the MoS2-PVK/PMMA film. These values are among the highest reported for MoS2-based nonlinear optical materials. These results show that covalent functionalization of MoS2 with polymers is an effective way to improve nonlinear optical responses for efficient optical limiting devices. PMID- 26891472 TI - L1 syndrome diagnosis complemented with functional analysis of L1CAM variants located to the two N-terminal Ig-like domains. AB - L1CAM gene mutations cause neurodevelopmental disorders collectively termed L1 syndrome. Insufficient information about L1CAM variants complicates clinical prognosis, genetic diagnosis and genetic counseling. We combined clinical data, in silico effect predictions and functional analysis of four L1CAM variants, p.I37N, p.T38M, p.M172I and p.D202Y, located to the two N-terminal Ig-like domains present in five families with symptoms of L1 syndrome. Software tools predicted destabilizing effects of p.I37N and p.D202Y but results for p.T38M and p.M172I were inconsistent. Cell surface expression of mutant proteins L1-T38M, L1 M172I and L1-D202Y was normal. Conversely, L1-I37N accumulated in the endoplasmic reticulum (ER) and showed temperature-sensitive protein maturation suggesting that p.I37N induces protein misfolding. L1CAM-mediated cell-cell aggregation was severely impaired by L1CAM variants p.I37N, p.M172I and p.D202Y but was preserved by the variant p.T38M. Our experimental data indicate that protein misfolding and accumulation in the ER affect function of the L1CAM variant p.I37N whereas the variants p.M172I and p.D202Y impair homophilic interaction at the cell surface. PMID- 26891473 TI - Enhancement of finger motion range with compliant anthropomorphic joint design. AB - Robotic researchers have been greatly inspired by the human hand in the search to design and build adaptive robotic hands. Especially, joints have received a lot of attention upon their role in maintaining the passive compliance that gives the fingers flexibility and extendible motion ranges. Passive compliance, which is the tendency to be employed in motion under the influence of an external force, is the result of the stiffness and the geometrical constraints of the joints that define the direction of the motion. Based on its building elements, human finger joints have multi-directional passive compliance which means that they can move in multiple axis of motion under external force. However, due to their complex anatomy, only simplified biomechanical designs based on physiological analysis are preferred in present day robotics. To imitate the human joints, these designs either use fixed degree of freedom mechanisms which substantially limit the motion axes of compliance, or soft materials that can deform in many directions but hinder the fingers' force exertion capacities. In order to find a solution that lies between these two design approaches, we are using anatomically correct finger bones, elastic ligaments and antagonistic tendons to build anthropomorphic joints with multi-directional passive compliance and strong force exertion capabilities. We use interactions between an index finger and a thumb to show that our joints allow the extension of the range of motion of the fingers up to 245% and gripping size to 63% which can be beneficial for mechanical adaptation in gripping larger objects. PMID- 26891474 TI - Classifying continuous, real-time e-nose sensor data using a bio-inspired spiking network modelled on the insect olfactory system. AB - In many application domains, conventional e-noses are frequently outperformed in both speed and accuracy by their biological counterparts. Exploring potential bio inspired improvements, we note a number of neuronal network models have demonstrated some success in classifying static datasets by abstracting the insect olfactory system. However, these designs remain largely unproven in practical settings, where sensor data is real-time, continuous, potentially noisy, lacks a precise onset signal and accurate classification requires the inclusion of temporal aspects into the feature set. This investigation therefore seeks to inform and develop the potential and suitability of biomimetic classifiers for use with typical real-world sensor data. Taking a generic classifier design inspired by the inhibition and competition in the insect antennal lobe, we apply it to identifying 20 individual chemical odours from the timeseries of responses of metal oxide sensors. We show that four out of twelve available sensors and the first 30 s (10%) of the sensors' continuous response are sufficient to deliver 92% accurate classification without access to an odour onset signal. In contrast to previous approaches, once training is complete, sensor signals can be fed continuously into the classifier without requiring discretization. We conclude that for continuous data there may be a conceptual advantage in using spiking networks, in particular where time is an essential component of computation. Classification was achieved in real time using a GPU accelerated spiking neural network simulator developed in our group. PMID- 26891475 TI - Human Mesenchymal Stromal Cells Improve Cardiac Perfusion in an Ovine Immunocompetent Animal Model. AB - BACKGROUND: Mesenchymal stromal cells (MSCs) hold considerable promise in the treatment of ischemic heart disease. Most preclinical studies of MSCs for acute myocardial infarction (AMI) have been performed either in syngeneic animal models or with human cells in xenogeneic immunodeficient animals. A preferable pre clinical model, however, would involve human MSCs in an immunocompetent animal. METHODS: AMI was generated in adult sheep by inducing ischemia reperfusion of the second diagonal branch. Sheep (n = 10) were randomized to receive an intravenous injection of human MSCs (1 * 10(6) cells/kg) or phosphate buffered saline. Cardiac function and remodeling were evaluated with echocardiography. Perfusion scintigraphy was used to identify sustained myocardial ischemia. Interaction between human MSCs and ovine lymphocytes was assessed by a mixed lymphocyte response (MLR). RESULTS: Sheep receiving human MSCs showed significant improvement in myocardial perfusion at 1 month compared with baseline measurements. There was no change in ventricular dimensions in either group after 1 month of AMI. No adverse events or symptoms were observed in the sheep receiving human MSCs. The MLR was negative. CONCLUSION: The immunocompetent ovine AMI model demonstrates the clinical safety and efficacy of human MSCs. The human cells do not appear to be immunogenic, further suggesting that immunocompetent sheep may serve as a suitable pre-clinical large animal model for testing human MSCs. PMID- 26891476 TI - Zebrafish response to 3D printed shoals of conspecifics: the effect of body size. AB - Recent progress in three-dimensional (3D) printing technology has enabled rapid prototyping of complex models at a limited cost. Virtually every research laboratory has access to a 3D printer, which can assist in the design and implementation of hypothesis-driven studies on animal behavior. In this study, we explore the possibility of using 3D printing technology to understand the role of body size in the social behavior of the zebrafish model organism. In a dichotomous preference test, we study the behavioral response of zebrafish to shoals of 3D printed replicas of varying size. We systematically vary the size of each replica without altering the coloration, aspect ratio, and stripe patterns, which are all selected to closely mimic zebrafish morphophysiology. The replicas are actuated through a robotic manipulator, mimicking the natural motion of live subjects. Zebrafish preference is assessed by scoring the time spent in the vicinity of the shoal of replicas, and the information theoretic construct of transfer entropy is used to further elucidate the influence of the replicas on zebrafish motion. Our results demonstrate that zebrafish adjust their behavior in response to variations in the size of the replicas. Subjects exhibit an avoidance reaction for larger replicas, and they are attracted toward and influenced by smaller replicas. The approach presented in this study, integrating 3D printing technology, robotics, and information theory, is expected to significantly aid preclinical research on zebrafish behavior. PMID- 26891477 TI - Bio-inspired fabrication of stimuli-responsive photonic crystals with hierarchical structures and their applications. AB - When the constitutive materials of photonic crystals (PCs) are stimuli responsive, the resultant PCs exhibit optical properties that can be tuned by the stimuli. This can be exploited for promising applications in colour displays, biological and chemical sensors, inks and paints, and many optically active components. However, the preparation of the required photonic structures is the first issue to be solved. In the past two decades, approaches such as microfabrication and self-assembly have been developed to incorporate stimuli responsive materials into existing periodic structures for the fabrication of PCs, either as the initial building blocks or as the surrounding matrix. Generally, the materials that respond to thermal, pH, chemical, optical, electrical, or magnetic stimuli are either soft or aggregate, which is why the manufacture of three-dimensional hierarchical photonic structures with responsive properties is a great challenge. Recently, inspired by biological PCs in nature which exhibit both flexible and responsive properties, researchers have developed various methods to synthesize metals and metal oxides with hierarchical structures by using a biological PC as the template. This review will focus on the recent developments in this field. In particular, PCs with biological hierarchical structures that can be tuned by external stimuli have recently been successfully fabricated. These findings offer innovative insights into the design of responsive PCs and should be of great importance for future applications of these materials. PMID- 26891471 TI - Forging Colloidal Nanostructures via Cation Exchange Reactions. AB - Among the various postsynthesis treatments of colloidal nanocrystals that have been developed to date, transformations by cation exchange have recently emerged as an extremely versatile tool that has given access to a wide variety of materials and nanostructures. One notable example in this direction is represented by partial cation exchange, by which preformed nanocrystals can be either transformed to alloy nanocrystals or to various types of nanoheterostructures possessing core/shell, segmented, or striped architectures. In this review, we provide an up to date overview of the complex colloidal nanostructures that could be prepared so far by cation exchange. At the same time, the review gives an account of the fundamental thermodynamic and kinetic parameters governing these types of reactions, as they are currently understood, and outlines the main open issues and possible future developments in the field. PMID- 26891478 TI - Highly efficient blue and warm white organic light-emitting diodes with a simplified structure. AB - Two blue fluorescent emitters were utilized to construct simplified organic light emitting diodes (OLEDs) and the remarkable difference in device performance was carefully illustrated. A maximum current efficiency of 4.84 cd A(-1) (corresponding to a quantum efficiency of 4.29%) with a Commission Internationale de l'Eclairage (CIE) coordinate of (0.144, 0.127) was achieved by using N,N diphenyl-4"-(1-phenyl-1H-benzo[d]imidazol-2-yl)-[1, 1':4', 1"-terphenyl]-4-amine (BBPI) as a non-doped emission layer of the simplified blue OLEDs without carrier transport layers. In addition, simplified fluorescent/phosphorescent (F/P) hybrid warm white OLEDs without carrier-transport layers were fabricated by utilizing BBPI as (1) the blue emitter and (2) the host of a complementary yellow phosphorescent emitter (PO-01). A maximum current efficiency of 36.8 cd A(-1) and a maximum power efficiency of 38.6 lm W(-1) were achieved as a result of efficient energy transfer from the host to the guest and good triplet exciton confinement on the phosphorescent molecules. The blue and white OLEDs are among the most efficient simplified fluorescent blue and F/P hybrid white devices, and their performance is even comparable to that of most previously reported complicated multi-layer devices with carrier-transport layers. PMID- 26891479 TI - Nanoporous capsules of block co-polymers of [(MeO-PEG-NH)-b-(L-GluA)]-PCL for the controlled release of anticancer drugs for therapeutic applications. AB - Herein, new nanoporous capsules of the block co-polymers of MeO-PEG-NH-(L-GluA)10 and polycaprolactone (PCL) have been synthesized through a surfactant-free cost effective self-assembled soft-templating approach for the controlled release of drugs and for therapeutic applications. The nanoporous polymer capsules are designed to be biocompatible and are capable of encapsulating anticancer drugs (e.g., doxorubicin hydrochloride (DOX) and imatinib mesylate (ITM)) with a high extent (~279 and ~480 ng MUg(-1), respectively). We have developed a nanoformulation of porous MeO-PEG-NH-(L-GluA)10-PCL capsules with DOX and ITM. The porous polymer nanoformulations have been programmed in terms of the release of anticancer drugs with a desired dose to treat the leukemia (K562) and human carcinoma cells (HepG2) in vitro and show promising IC50 values with a very high mortality of cancer cells (up to ~96.6%). Our nanoformulation arrests the cell divisions due to 'cellular scenescence' and kills the cancer cells specifically. The present findings could enrich the effectiveness of idiosyncratic nanoporous polymer capsules for use in various other nanomedicinal and biomedical applications, such as for killing cancer cells, immune therapy, and gene delivery. PMID- 26891480 TI - Small interfering RNA delivery through positively charged polymer nanoparticles. AB - Small interfering RNA (siRNA) is receiving increasing attention with regard to the treatment of many genetic diseases, both acquired and hereditary, such as cancer and diabetes. Being a high molecular weight (MW) polyanion, siRNA is not able to cross a cell membrane, and in addition it is unstable in physiological conditions. Accordingly, a biocompatible nanocarrier able to deliver siRNA into cells is needed. In this work, we synthesized biocompatible positively charged nanoparticles (NPs) following a two-step process that involves ring opening polymerization (ROP) and emulsion free radical polymerization (EFRP). Firstly, we proved the possibility of fine tuning the NPs' characteristics (e.g. size and surface charge) by changing the synthetic process parameters. Then the capability in loading and delivering undamaged siRNA into a cancer cell cytoplasm has been shown. This latter process occurs through the biodegradation of the polymer constituting the NPs, whose kinetics can be tuned by adjusting the polymer's MW. Finally, the ability of NPs to carry siRNA inside the cells in order to inhibit their target gene has been demonstrated using green flourescent protein positive cells. PMID- 26891481 TI - In situ nanojoining of Y- and T-shaped silver nanowires structures using femtosecond laser radiation. AB - We report the in situ joining of spatially separated silver nanowires without additional filler material by controlled irradiation with femtosecond laser pulses. Nanojoining under these conditions arises from highly localized heat generation in the vicinity of the gap between adjacent silver nanowires. Melting, followed by the flow of silver into the gap, is optimized by adjusting the direction of laser polarization relative to gap geometry. Our results show that melting of silver occurs on both nanowires in the vicinity of the gap between the two components. Successful formation of a joint is found to be a function of the angle between the long axis of the nanowires and the gap distance. Finite element simulations show that the strong localized electric field generated by optical excitation determines the location and the morphology of the resulting bond. Light coupling and the resulting emission properties of these Y-shaped nanowire structures have been simulated and are compared to similar structures where the gap remains open. It is suggested that joined Y-shaped couplers will have a higher switching ratio between emitted nanowire ends than those occurring in open gap structures. Nanojoining induced by localized heating under strong field excitation may enable the production of robust branched metal nanowire structures for optical applications. PMID- 26891482 TI - Reconstructing Curvilinear Networks Using Path Classifiers and Integer Programming. AB - We propose a novel approach to automated delineation of curvilinear structures that form complex and potentially loopy networks. By representing the image data as a graph of potential paths, we first show how to weight these paths using discriminatively-trained classifiers that are both robust and generic enough to be applied to very different imaging modalities. We then present an Integer Programming approach to finding the optimal subset of paths, subject to structural and topological constraints that eliminate implausible solutions. Unlike earlier approaches that assume a tree topology for the networks, ours explicitly models the fact that the networks may contain loops, and can reconstruct both cyclic and acyclic ones. We demonstrate the effectiveness of our approach on a variety of challenging datasets including aerial images of road networks and micrographs of neural arbors, and show that it outperforms state-of the-art techniques. PMID- 26891483 TI - Deep Independence Network Analysis of Structural Brain Imaging: Application to Schizophrenia. AB - Linear independent component analysis (ICA) is a standard signal processing technique that has been extensively used on neuroimaging data to detect brain networks with coherent brain activity (functional MRI) or covarying structural patterns (structural MRI). However, its formulation assumes that the measured brain signals are generated by a linear mixture of the underlying brain networks and this assumption limits its ability to detect the inherent nonlinear nature of brain interactions. In this paper, we introduce nonlinear independent component estimation (NICE) to structural MRI data to detect abnormal patterns of gray matter concentration in schizophrenia patients. For this biomedical application, we further addressed the issue of model regularization of nonlinear ICA by performing dimensionality reduction prior to NICE, together with an appropriate control of the complexity of the model and the usage of a proper approximation of the probability distribution functions of the estimated components. We show that our results are consistent with previous findings in the literature, but we also demonstrate that the incorporation of nonlinear associations in the data enables the detection of spatial patterns that are not identified by linear ICA. Specifically, we show networks including basal ganglia, cerebellum and thalamus that show significant differences in patients versus controls, some of which show distinct nonlinear patterns. PMID- 26891484 TI - AggNet: Deep Learning From Crowds for Mitosis Detection in Breast Cancer Histology Images. AB - The lack of publicly available ground-truth data has been identified as the major challenge for transferring recent developments in deep learning to the biomedical imaging domain. Though crowdsourcing has enabled annotation of large scale databases for real world images, its application for biomedical purposes requires a deeper understanding and hence, more precise definition of the actual annotation task. The fact that expert tasks are being outsourced to non-expert users may lead to noisy annotations introducing disagreement between users. Despite being a valuable resource for learning annotation models from crowdsourcing, conventional machine-learning methods may have difficulties dealing with noisy annotations during training. In this manuscript, we present a new concept for learning from crowds that handle data aggregation directly as part of the learning process of the convolutional neural network (CNN) via additional crowdsourcing layer (AggNet). Besides, we present an experimental study on learning from crowds designed to answer the following questions. 1) Can deep CNN be trained with data collected from crowdsourcing? 2) How to adapt the CNN to train on multiple types of annotation datasets (ground truth and crowd based)? 3) How does the choice of annotation and aggregation affect the accuracy? Our experimental setup involved Annot8, a self-implemented web-platform based on Crowdflower API realizing image annotation tasks for a publicly available biomedical image database. Our results give valuable insights into the functionality of deep CNN learning from crowd annotations and prove the necessity of data aggregation integration. PMID- 26891485 TI - Image Segmentation Using Parametric Contours With Free Endpoints. AB - In this paper, we introduce a novel approach for active contours with free endpoints. A scheme for image segmentation is presented based on a discrete version of the Mumford-Shah functional where the contours can be both closed and open curves. Additional to a flow of the curves in normal direction, evolution laws for the tangential flow of the endpoints are derived. Using a parametric approach to describe the evolving contours together with an edge-preserving denoising, we obtain a fast method for image segmentation and restoration. The analytical and numerical schemes are presented followed by numerical experiments with artificial test images and with a real medical image. PMID- 26891486 TI - Graph-Based Compression of Dynamic 3D Point Cloud Sequences. AB - This paper addresses the problem of compression of 3D point cloud sequences that are characterized by moving 3D positions and color attributes. As temporally successive point cloud frames share some similarities, motion estimation is key to effective compression of these sequences. It, however, remains a challenging problem as the point cloud frames have varying numbers of points without explicit correspondence information. We represent the time-varying geometry of these sequences with a set of graphs, and consider 3D positions and color attributes of the point clouds as signals on the vertices of the graphs. We then cast motion estimation as a feature-matching problem between successive graphs. The motion is estimated on a sparse set of representative vertices using new spectral graph wavelet descriptors. A dense motion field is eventually interpolated by solving a graph-based regularization problem. The estimated motion is finally used for removing the temporal redundancy in the predictive coding of the 3D positions and the color characteristics of the point cloud sequences. Experimental results demonstrate that our method is able to accurately estimate the motion between consecutive frames. Moreover, motion estimation is shown to bring a significant improvement in terms of the overall compression performance of the sequence. To the best of our knowledge, this is the first paper that exploits both the spatial correlation inside each frame (through the graph) and the temporal correlation between the frames (through the motion estimation) to compress the color and the geometry of 3D point cloud sequences in an efficient way. PMID- 26891488 TI - Stochastic Optimal Regulation of Nonlinear Networked Control Systems by Using Event-Driven Adaptive Dynamic Programming. AB - In this paper, an event-driven stochastic adaptive dynamic programming (ADP) based technique is introduced for nonlinear systems with a communication network within its feedback loop. A near optimal control policy is designed using an actor-critic framework and ADP with event sampled state vector. First, the system dynamics are approximated by using a novel neural network (NN) identifier with event sampled state vector. The optimal control policy is generated via an actor NN by using the NN identifier and value function approximated by a critic NN through ADP. The stochastic NN identifier, actor, and critic NN weights are tuned at the event sampled instants leading to aperiodic weight tuning laws. Above all, an adaptive event sampling condition based on estimated NN weights is designed by using the Lyapunov technique to ensure ultimate boundedness of all the closed loop signals along with the approximation accuracy. The net result is event driven stochastic ADP technique that can significantly reduce the computation and network transmissions. Finally, the analytical design is substantiated with simulation results. PMID- 26891487 TI - Movement Anticipation and EEG: Implications for BCI-Contingent Robot Therapy. AB - Brain-computer interfacing is a technology that has the potential to improve patient engagement in robot-assisted rehabilitation therapy. For example, movement intention reduces mu (8-13 Hz) oscillation amplitude over the sensorimotor cortex, a phenomenon referred to as event-related desynchronization (ERD). In an ERD-contingent assistance paradigm, initial BCI-enhanced robotic therapy studies have used ERD to provide robotic assistance for movement. Here we investigated how ERD changed as a function of audio-visual stimuli, overt movement from the participant, and robotic assistance. Twelve unimpaired subjects played a computer game designed for rehabilitation therapy with their fingers using the FINGER robotic exoskeleton. In the game, the participant and robot matched movement timing to audio-visual stimuli in the form of notes approaching a target on the screen set to the consistent beat of popular music. The audio visual stimulation of the game alone did not cause ERD, before or after training. In contrast, overt movement by the subject caused ERD, whether or not the robot assisted the finger movement. Notably, ERD was also present when the subjects remained passive and the robot moved their fingers to play the game. This ERD occurred in anticipation of the passive finger movement with similar onset timing as for the overt movement conditions. These results demonstrate that ERD can be contingent on expectation of robotic assistance; that is, the brain generates an anticipatory ERD in expectation of a robot-imposed but predictable movement. This is a caveat that should be considered in designing BCIs for enhancing patient effort in robotically-assisted therapy. PMID- 26891489 TI - [Frontline of vascular regenerative therapy for refractory peripheral arterial diseases]. PMID- 26891490 TI - [Trends in vocal cord surgery]. PMID- 26891491 TI - [Impact of Kampo medicine upon the field of otorhinolaryngology--from head-and neck neoplasms to otitis media]. PMID- 26891492 TI - [Pathophysiology of Meniere's disease--point of views from the study on endolymphatic sac]. PMID- 26891493 TI - [Diagnosis of and therapy for dizziness]. PMID- 26891494 TI - [New standard of cochlear implantation for children]. PMID- 26891496 TI - [New therapeutic strategy for head-and-neck neoplasms]. PMID- 26891495 TI - [New molecular target therapy for thyroid neoplasms and malignant melanomas]. PMID- 26891497 TI - Looking forward. PMID- 26891499 TI - 2016 CPT coding changes and their effects. PMID- 26891498 TI - Provisions in the 2016 Medicare physician fee schedule that will affect surgical practice: An overview. PMID- 26891501 TI - Statement on the aging surgeon. PMID- 26891500 TI - The 2015 RAS-ACS annual Communications Committee essay contest: An introduction. PMID- 26891502 TI - Statement on older adult burn prevention. PMID- 26891503 TI - Statement on prevention of non-traffic vehicle-related injuries in children. PMID- 26891504 TI - Statement on safety belt laws and enforcement. PMID- 26891505 TI - The one-year grace period for correct use of ICD-10 codes. PMID- 26891506 TI - ACS Advisory Council for Rural Surgery hard at work. PMID- 26891507 TI - The defeat of Proposition 46 in California: A case study of successful surgeon advocacy. PMID- 26891508 TI - Rectal cancer resection: Laparoscopic or open--which way forward?. PMID- 26891509 TI - Dr. Charles McBurney: A pioneer in the surgical treatment of appendicitis. PMID- 26891511 TI - Antibiotic resistance causing issues for surgical patients. PMID- 26891510 TI - Dr. and Mrs. M. J. Jurkiewicz: A distinctive legacy of giving. PMID- 26891512 TI - NTDB data points: Annual report 2015: regional trauma. PMID- 26891513 TI - In memoriam: Dr. Isidore Cohn, Jr.: A life well-lived. PMID- 26891514 TI - High prevalence of Plasmodium falciparum pfcrt K76T mutation in children with sickle cell disease at a tertiary hospital in north-western Tanzania. AB - The high prevalence of sickle cell disease (SCD) and trait in Sub-Saharan Africa coincides with the distribution of Plasmodiumfalciparum malaria. Due to prolonged heavy use of chloroquine (CQ) as an antimalarial, drug resistance has developed. Many countries including Tanzania abandoned the use of CQ for uncomplicated malaria, except its use as prophylaxis in patients with sickle cell disease. This study investigated the prevalence of malaria in SCD patients and mutations associated with CQ resistance. Children diagnosed with sickle cell disease attending both outpatient clinic and those admitted at Bugando Medical Centre in northwestern Tanzania were screened for malaria using thick blood smear. A dried blood spot on Whatman filter paper was also taken for polymerase chain reaction (PCR) and restriction fragment length polymorphism. Among 123 known patients with sickle cell disease, the prevalence of malaria by blood smear microscopy was 3.2% and by PCR was 13.8%. The prevalence of K76T mutation among the patients was 81.3%. The majority of the patients (72.4%) were using chloroquine prophylaxis. In conclusion, the prevalence of malaria parasitaemia among children with sickle cell disease attending BMC is low (3.2%) by microscopy but several children maintain sub patent infection detectable by PCR. The prevalence of chloroquine resistant P falciparum in these children was higher than that previously seen in normal population in Tanzania. We recommend special attention to be paid to patients with sickle cell disease while studying the dynamics of drug resistant parasites. PMID- 26891515 TI - Profile of plasma lipids and degree of derangements among the elderly of Morogoro region, Tanzania. AB - Changes in lifestyles and ageing have been associated with growing rates of modifiable cardiovascular risk factors (CRF). Dyslipidemia is one ofthe CRF associated with numbers of cardiovascular diseases. This descriptive cross sectional study was conducted to determine the profile and degree of derangements of plasma lipids among 300 (176 females and 124 males) elderly individuals aged >= 60 years in Morogoro, Tanzania. The calorimetric enzymatic methods and the Friedewal's equation were used for determination of cholesterols and triglycerides (TG). Social and demographic characteristics were gathered by structured questionnaires. The logistic regression models were used to identify the determinants of abnormal serum lipids level. Mean Total Cholesterols (TC) and Low Density Lipoprotein Cholesterols (LDL-C) in females exceeded significantly that of males. Mean TC, LDL-C as well as TG (mg/dL) declined significantly with age while mean High Density Lipoprotein Cholesterols (HDL-C) also declined but only slightly. Elderly females were two times more likely to have elevated TC (OR = 2.11; 95% CI: 1.04-4.28: P = 0.05) and LDL-C (OR = 2.15; 95% CI: 1.17- 3.97: P = 0.019) and three times to have lowered HDL-C (OR = 3; 95% CI: 1.97-5.30: P < 0.001) than males. Urban residents were about two times more likely to have elevated LDL-C (OR = 1.84; 95% CI: 1.04-3.25: P = 0.047) than their rural counterparts. Body Mass Index of >= 30 kg/m2 was also associated with elevated LDL-C (OR = 1.89; 95% CI: 1.05-3.42: P = 0.045) and lowered HDL-C (OR = 2.18; 95% CI: 1.3-3.65: P = 0.004), respectively. The present study has established the profile and level of derangements of serum lipids among the elderly of Morogoro region in Tanzania. It appears that, female sex and BMI of >= 30 kg/m2 are significant factors for elevated TC, LDL-C and lowered HDL-C while urban life is a significant factor for elevated LDL-C. PMID- 26891516 TI - Assessment of physicochemical characteristics and hygienic practices along the value chain of raw fruit juice vended in Dar es Salaam City, Tanzania. AB - Fresh fruit juice is an essential component of human diet and there is considerable evidence of health and nutritional benefits. However, nature of the fruits used in juicing and unhygienic processes in the value chain may cause poor quality of juice. This cross- sectional study was conducted to assess physicochemical characteristics and hygienic practices along the value chain of raw fruit juice vended in Dar es Salaam, Tanzania. A total of 90 juice vendors were interviewed. Ninety juice samples were collected and analysed for physicochemical quality. The pH of juices ranged between 2.7 and 6.4, acidity 0.01% and 1.3% and, total soluble solids ranged between -1.5 and 18.04 degrees Brix. Most juices (67.8%) had -Brix levels below Codex recommended values classified as weak and watery. Juices were made of mango, passion, tamarind, sugar cane and mixture of these fruits sourced from open markets in the city. Water for washing of fruits and dilution of juices was from deep wells (53.3%) and taps (46.7%). About one third (37.8%) of the juice vendors didn't wash the fruits before juicing and 44.4% didn't boil water for juice dilution. Juice extraction was done by kitchen blenders, boiling in water and squeezing by simple machines. Juice pasteurization was not done. The majority of vendors (78.9%) stored juices in plastic buckets and juice was sold in glass cups, reused plastic bottles and disposable cups. Vending sites were restaurants, bus stands and along roadsides. The majority of premises (78.9%) were in unhygienic condition that likely encouraged or introduced contaminants to the juices. It is concluded that, the overall handling, preparation practices and physicochemical quality of raw fruit juices vended in Dare es Salaam City are poor. The government should educate the vendors on food safety and hygiene as well as enforcing regular monitoring of the quality of street fruit juices. PMID- 26891517 TI - Injury outcome among helmeted and non-helmeted motorcycle riders and passengers at a tertiary care hospital in north-western Tanzania. AB - Motorcycle helmets have been reported to reduce the risk of death and head injuries following motorcycle accidents. The aim of this descriptive prospective study was to determine the injury outcome among helmeted and non-helmeted motorcyclists and passengers at a tertiary hospital in north-western Tanzania. A total of 654 patients involved in the motorcycle accident were studied. Of these, 468 (71.6%) were motorcyclists (riders) and the remaining 186 (28.4%) were passengers. The median age of patients at presentation was 26 years. Male outnumbered females by a ratio of 4.5: 1. Helmet use was reported in 312 (47.7%) patients. Non- helmeted patients were young compared with helmeted patients and this was statistically significant (p = 0.021). The rate of helmet use was significantly higher among motorcyclists than among passengers (p = 0.004). History of alcohol consumption prior to the accident was reported in 212 (32.4%) patients. The rate of helmet use was significantly low among alcohol consumers compared with non-alcohol consumers (p = 0.011). Lack of helmet use was significantly associated with abnormal head Computed Tomography scans, admission to the Intensive care unit, severe trauma, and worse traumatic brain injury severity (p < 0.001). Helmet use was significantly associated with shorter period of hospitalization and reduced mortality rate (p < 0.001). Motorcycle helmet use is still low in this part of Tanzania and this poses a great impact on injury outcome among motorcycle injury patients. This observation calls for action to implement more widespread injury prevention and helmet safety education and advocacy. PMID- 26891518 TI - Aetiological agents of surgical site infection in a specialist hospital in Kano, north-western Nigeria. AB - Despite the advances made in asepsis, antimicrobial drugs, sterilization and operative techniques, surgical site infections (SSI) continue to be a major problem in all branches of surgery in the hospitals. The objective of this study was to establish the incidence of SSI, the type and frequency of various pathogens and their antibiotic susceptibility pattern in Murtala Mohammed Specialist Hospital (MMSH), Kano, Nigeria. A total of 2,920 consecutive patients who underwent different surgical procedures between January 2009 and December 2010 at Murtala Mohammed Specialist Hospital were enrolled in this study. Samples of pus were collected from infected cases and screened for bacterial and fungal pathogens by standard microbiological methods. Antibiotic susceptibility tests were done by disc diffusion technique. A total 878 patients were found to be clinically infected and 919 isolates were obtained in all. This gave an incidence of 30.1% infection rate. While 783 (89.2%) cultures yielded single organism, 77 (9.8%) yielded mixed growth and 18(8.1%) cultures yielded no growth. The most frequently isolated organism was E. coli (25.5%) followed by Staphylococcus aureus 20.6%. The incidence of Methicillin resistant Staphylococcus aureus was 35.7%. Ceftriaxone, ceftazidime and ofloxacin showed good results against most isolates while ampicillin and cotrimoxazole which are commonly used drugs were ineffective. An understanding of the various types of pathogen involved in SSI and their antibiotic susceptibility pattern will reduce indiscriminate prescription of antibiotics and help in infection control. PMID- 26891519 TI - Knowledge, attitudes and acceptability to provider-initiated HIV testing and counseling: patients' perspectives in Moshi and Rombo Districts, Tanzania. AB - Provider-initiated HIV testing and counseling (PITC) is referred to as routine testing in a clinical setting as part of a standard programme of medical services. PITC is initiated in order to avoid missed opportunities for people to get tested for HIV. While advocated as a strategy, there is dearth of information on patients' views on PITC in a number of districts in Tanzania. The objective of this study was to assess the knowledge, attitude and acceptability to PITC services among patients attending health care facilities in rural and urban settings in Kilimanjaro region A total of 12 focus group discussions (FGDs) were conducted with 99 (73 female and 26 male) patients enrolled into out-patient clinics in 8 (2 hospitals and 6 primary care centers) health facilities in Moshi Urban and Rombo districts in northern Tanzania. The study explored on knowledge, attitudes and acceptability of PITC, perceived benefits and barriers of PITC, and ethical issues related to PITC. Interviews were audio taped, transcribed, translated, and analyzed using Non-numerical Unstructured Data Indexing and Theorizing (NUDIST) software. Knowledge about PITC services was generally low. Compared to men, women had a more positive attitude towards PITC services, because of its ability to identify and treat undiagnosed HIV cases. HIV stigma was regarded as a major barrier to patients' uptake of PITC. Institutional factors such as lack of supplies and human resources were identified as barriers to successful provision of PITC. In conclusion, the findings highlight both opportunities and potential barriers in the successful uptake of PITC, and underscore the importance of informed consent, counseling and confidentiality and the need for specific strategies on advocacy for the service. PMID- 26891520 TI - Overweight, obesity and perceptions about body weight among primary schoolchildren in Dar es Salaam, Tanzania. AB - The increasing prevalence of overweight and obesity among children has become a public health concern both in developing and developed countries. Previous research studies have shown that favourable perception of one's body weight is an important factor in weight control. This study determined prevalence of overweight and obesity and assessed perception about body weight among primary schoolchildren in Dar es Salaam, Tanzania. In this cross sectional study, nine schools were selected randomly from a list of all primary schools in Dar es Salaam. A structured questionnaire was used to collect data on socio-demographic characteristics and lifestyle information including perception about body weight. Height and weight were measured following standard procedures. Chi- square tests and multiple logistic regressions were used to determine factors which influence perceptions about body weight. A total of 446 children were included into the study. The mean body mass index (BMI) was 16.6 +/- 4.0 kg/m2 (16.1 +/- 4.0 for males and 17.0 +/- 4.0 for females). Prevalence of overweight and obesity was 9.8% and 5.2%, respectively. The prevalence of overweight and obesity was significantly higher among girls, 13.1% and 6.3% compared to boys with 6.3% and 3.8% overweight and obese respectively (P=0.0314). Overall, the prevalence of overweight and obesity was 15.0% (10.1% among boys and 19.4% among girls). One third (33.3%) of the children perceived their body weight as overweight or obese. Among overweight and obese children, 35.4% had unfavourable perception of their body weights. There was a statistically significant difference between perceived body weight and actual body weight as indicated by BMI for both boys and girls (P < 0.05). Age of the child (AOR = 0.55 95% CI 0.36-0.85) and area of residence (COR = 0.64 95% CI 0.44-0.95) were found to be significant predictors of favourable perception of one's body weight. In conclusion, the prevalence of overweight and obesity is not very high in this population. However over a third of overweight and obese children, had unfavourable perception of their body weights. We recommend targeted educational programmes about overweight and obesity and the associated health effects in order to instil a behaviour of self consciousness on overweight and obesity among children in Tanzania. PMID- 26891521 TI - Influence of pregnancy perceptions on patterns of seeking antenatal care among women in reproductive age of Masaka District, Uganda. AB - Maternal mortality remains a challenge in Sub-Saharan Africa including Uganda. Antenatal Care (ANC) is one of the recommended measures to improve maternal and child health. However, the influence of pregnancy definition and perception on patterns of seeking regular and timely antenatal care among women in the reproductive age group (15-49 years) is not known. The objectives of this study were to: (i) understand the women's social definitions and perceptions on their pregnancy; (ii) understand the socio-cultural beliefs related to pregnancy among women of the reproductive age group; and, (iii) examine the influence of social definitions, perceptions and beliefs about pregnancy on women's antenatal care seeking behaviour patterns to inform the decentralised health care delivery system in Uganda. A total of 45 women, mothers and expectant women who were purposively selected from Kimanya sub county of Masaka district in Uganda participated in the study. Ten key informant interviews and four Focus Group Discussions (FGDs) were also conducted. Key findings indicate that the women's socio-definitions and perceptions of pregnancy influence their seeking behaviour on antenatal health care. To the women with a positive orientation towards antenatal care, pregnancy provides joy, happiness, pride, promotes their social status and safe-guards their marriage. Pregnancy is rewarding with care, love, support and gifts. Women who shun antenatal care perceive pregnancy to be a source of misery, sadness, pain and suffering. It is an uncomfortable and regrettable experience. Women also hold socio-cultural beliefs on pregnancy, which are culturally constructed and rooted in taboos, rituals and practices of their communities. It is therefore important to sensitise women and those who attend to them when they are pregnant to understand these perceptions and definitions to motivate them to seek antenatal and postnatal care for better maternal and child health. PMID- 26891522 TI - Living with vesico-vaginal fistula: experiences of women awaiting repairs in Ebonyi State, Nigeria. AB - Vesico-vaginal fistula (VVF) is one of maternal health problems confronting public health workers in Nigeria today. Information on how women suffering from this condition cope is important in that it can inform the design and delivery of programmes and interventions to address the challenges that face victims of VVF. The objective of this study was to highlight how women living with VVF cope with the health problem in Ebonyi state, Nigeria. In-depth interviews were conducted with ten women awaiting repairs at the National Fistula Centre at Abakaliki in Nigeria. Six of the women have lived with the health problem for more than ten years. Findings show that nearly all the women attributed their health problem to supernatural causes. The women stated that they go through a lot of physical and emotional problems. Some of the ways they have devised of physically coping with the problem include bathing regularly and use of strips of old wrappers as pads. Many of them cope emotionally and financially by attending religious gatherings and having some form of income yielding business. The study recommends the need for repairs to go hand in hand with vocational training so that they will have some income yielding business after repairs. PMID- 26891523 TI - Increased tolerance of Anopheles gambiae s.s. to chemical insecticides after exposure to agrochemical mixture. AB - Resistance of mosquitoes to insecticides is mainly attributed to their adaptation to insecticide-based vector control interventions. Although pesticides used in agriculture have been frequently mentioned as an additional force driving the selection of resistance, only a few studies were dedicated to validate this hypothesis. The objective of this study was to investigate the effect of exposure of the malaria mosquito, Anopheles gambiae s.s. larvae for 72h to sub-lethal concentrations of the agrochemical mixture (pesticides, herbicides and fungicides). Their subsequent tolerances were measured to deltamethrin (pyrethroid), DDT (organochlorine) and bendiocarb (carbamate) currently used for vector control. The mean LC50 was determined and tolerance ratios for larvae exposed to agrochemical comparatively with unexposed larvae were calculated and expressed as fold increased tolerance. Bioassays revealed a significant increase in larval tolerance to detamethrin (1.83-2.86 fold), DDT (1.31-1.53 fold) and bendiocarb (1.14-1.19 fold) following exposure to 0.1 uM and 1 uM agrochemical mixture. The observed increased tolerance in this study is likely to be based on metabolic resistance mechanisms. Overall, this study reveals the potential of agrochemicals to increase the tolerance of mosquito larvae to chemical insecticides. PMID- 26891525 TI - The da Vinci robotic system in head and neck surgery. AB - Intuitive Surgical Inc. (Sunnyvale, Ca, USA) extended the use of the da Vinci robot to head and neck surgery in 2005 following the previous use in urological, gynecological and cardiothoracic surgery. It then gained wide popularity throughout the globe. Our aim is to describe the da Vinci Robot System and discuss its applications in head and neck surgery. Continued refinements and applications in robotic surgery for otolaryngology will in time be possible as new robotic procedures are developed for endolaryngeal work. PMID- 26891524 TI - Isolated tubercular hepatic abscess with diffuse pattern mimicking hepatocellular carcinoma in HIV positive patient: a case report. AB - Isolated hepatic tuberculosis presenting as a mass either with or without fever can be confused with hepatocellular carcinoma. Clinical examination and laboratory investigations are not specific. Radiological investigations such as ultrasound and computed tomography cannot confirm the diagnosis; hence it is vital to always make an effort to demonstrate presence of acid fast bacilli in aspirated pus or necrotic material from a liver mass. We present a case of 50 years old male patient with HIV/AIDS who presented with non-specific symptoms without fever, clinically with hepatomegaly mimicking hepatocellular carcinoma with metastasis. Abdominal ultrasound revealed a mass in the left liver lobe, with diffuse involvement in the right liver lobe. Liver mass histology showed granulomatous pattern with epitheloid cell aggregation. Aspirated blood from fine needle guided biopsy stained on Ziehl Neelsen for acid fast bacilli turned out positive. Clinical examination did not reveal lymphadenopathy, abdominal ultrasound also ruled out para-aortic lymphadenopathy, and chest x-ray was essentially normal. Evaluation of the patient six months after completing quadruple treatment for tuberculosis showed marked clinical improvement. The objective of this case report is to highlight the importance of considering hepatic tuberculosis as a differential diagnosis in cases of hepatomegaly and initiate appropriate investigations to rule out a possibility of Tuberculosis which is potentially treatable with early diagnosis. PMID- 26891526 TI - Transoral robotic surgery in head neck cancer management. AB - Head and Neck cancer can be treated by non-surgical or surgical modalities. Current surgical techniques include open surgery and transoral resections. The latter have the distinct advantage of quicker recovery and reduced hospital stay. The further down the aerodigestive tract tumours are sited, the more difficult is the transoral access, requiring techniques that combine magnification and finer instrumentation. Thus, while oral cavity tumours can be removed transorally without special equipment, the need to address oropharyngeal and laryngeal cancers led to the evolution of transoral laser microsurgery. Transoral robotic surgery (TORS) improves the visualisation, the instrumentation and the ergonomics in transoral resections and is also used primarily in the treatment of oropharyngeal and laryngeal cancer. Current evidence suggests that the oncologic and functional outcome of TORS surgery is good as speech and swallowing mechanisms are better preserved. This review will provide the reader an insight into the role of TORS in head and neck practice. PMID- 26891527 TI - Functional outcomes after transoral robotic surgery for squamous cell carcinoma of the oropharynx. AB - Over the past decade, the development of transoral robotic surgery (TORS) brought a new opportunity in the treatment of early T-stage oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to review the functional outcomes after TORS. Indeed, dysphagia is among the most commonly cited functional impairments in OPSCC survivors treated by surgeries with an open approach or conventional radiotherapy. We performed a review of the literature and analysed functional outcomes after TORS. Althought the technique is very recent, early functional and oncologic outcome data are promising and the major studies analysing these parameters support that TORS is feasible and safe as well as oncologically and functionally efficacious. PMID- 26891528 TI - Early experience in transoral robotic surgery (TORS) for non-oropharyngeal head and neck malignancies: a review of functional and oncologic outcomes. AB - OBJECTIVE: To review and summarize functional and oncologic outcomes after transoral robotic surgery (TORS) for non-oropharyngeal head and neck malignancies. DATA SOURCES: The MEDLINE database and bibliographies of relevant studies were searched through December 2014. METHODS: Search strategy was ((transoral) AND surgery) AND robotics) OR TORS. Abstracts and titles were screened for relevance and full articles of the selected records were evaluated and critically appraised after inclusion. Data concerning functional and oncologic outcomes as well as adverse effects were collected. RESULTS: 22 records were eventually included in the review. For TORS in the treatment of glottic, hypopharyngeal ands supraglottic cancer we retained 3 case series (26 patients), 5 case series (36 patients) and 6 case series (67 patients) respectively. 8 case reports/series (14 patients) assessing safety and feasibility of TORS for tumours in the parapharyngeal space, nasopharynx and skull base were also evaluated. In general, treatment of laryngeal and hypopharyngeal cancer by means of TORS seems to be feasible and safe with satisfying functional and short-term oncologic results. For treatment of malignant tumours in the parapharyngeal space, nasopharynx and skull base, the benefits of TORS, when compared to classic surgical techniques, are still uncertain and are particularly based on theoretical advantages. CONCLUSION: TORS offers an interesting new approach for treating non-oropharyngeal head and neck malignancies. However, long-term results are still not reported and TORS should be directly compared to existing therapeutic options in randomized controlled trials. Until then, its use should be subject to critical appraisal. PMID- 26891529 TI - TORS for head and neck squamous cell carcinoma (HNSCC): the Hamburg experience. AB - OBJECTIVE: To report 2.5-year survival outcomes for head and neck squamous cell carcinoma treated primarily with transoral robotic-assisted resection. PATIENTS AND METHODS: Fifty consecutive, appropriately staged patients were enrolled prospectively, and underwent transoral robotic surgery between September 2011 and August 2013. There were 18 patients with overall Stage I-II and 32 patients with Stage III-IV disease. Adjuvant treatment could be spared for 20 patients. Another 5 patients refused the recommended adjuvant treatment. Seventeen patients received 60 Gy adjuvant radiotherapy and 8 patients underwent 66 Gy adjuvant chemo-radiotherapy. RESULTS: Overall survival was 94% with two disease-specific deaths and one unrelated death. The 2.5-year disease free survival rate was 88%, and the 2.5-year recurrence-free survival was 80%. Local recurrence rate was 10% after 2.5 years. CONCLUSION: Using TORS as their primary modality, 40% of the patients did not need adjuvant treatment and showed similar survival rates to that of conventional surgery or primary chemoradiotherapy. In another 34% of the patients, adjuvant chemotherapy could be spared and adjuvant radiotherapy could be reduced by 10 Gy, compared to primary chemoradiotherapy of 70 Gy. This invited report is based on previously published data by the same authors. PMID- 26891530 TI - Clinical outcomes of transoral robotic surgery for supraglottic squamous cell carcinoma: experience of a french evaluation cooperative subgroup of gettec. AB - BACKGROUND: Transoral, minimally invasive, organ preservation surgeries are increasingly used to treat laryngopharyngeal carcinomas to avoid the toxicity associated with combined chemoradiotherapy regimens. This study investigated the efficiency, safety, and functional outcomes of using transoral robotic surgery (TORS) to perform supraglottic laryngectomy (SGL). METHODS: This was a multicenter study using a case series with planned data collection from 2009 to 2012 for patients with supraglottic squamous cell carcinomas (SCC) who underwent SGL using TORS. RESULTS: Eighty-four (84) of 262 patients underwent TORS for supraglottic SCC. Within 24 hours of surgery, 24% of the patients started on an oral diet. The median use of a feeding tube was 8 days for 76% of other patients. Definitive percutaneous gastrostomy feeding was necessary for 9.5% of the patients. 24% of the patients did require a tracheostomy, and the median use was 8 days. One percent (1%) of the patients had a definitive tracheostomy. Aspiration pneumonia was observed in 23% of the patients during the postoperative course, and was responsible for the death of one patient. Postoperative bleeding occurred in 18% of the patients. Based on the pathology results, 51% of the patients received adjuvant radiation therapy. CONCLUSION: TORS for SGL in intermediate stage SCC is a safe procedure with good functional outcomes and fast recovery times. However, adverse events can occur. Consequently, this technique requires good patient selection criteria to reduce the risk of postoperative complications. PMID- 26891532 TI - Transoral robotic tongue base reduction in surgical management of obstructive sleep apnea syndrome. AB - Management of base of tongue (BOT) is a challenging topic in surgical management of obstructive sleep apnea syndrome. After the introduction of transoral robotic surgery technology (TORS) into the otolaryngology practice, surgery on the BOT was performed more effectively. Base of tongue reduction can be performed alone or as a part of a multilevel surgery. Patient selection is important and will be discussed further in this study. Available studies show promising and encouraging results for TORS future use in BOT. PMID- 26891531 TI - Transoral robotic surgery for base of tongue neoplasms. AB - Surgery to the base of tongue (BOT) in the presence of neoplasm is a challenging topic for head and neck surgeons. This area is difficult to access and includes important neurovascular structures such as the hypoglossal nerve and lingual artery. The pivotal role of the tongue base in swallowing makes planning the surgical approach more challenging. The surgical approaches vary from open neck/mandibulotomy to transoral laser surgery (TLS) which have significant disadvantages. After introduction of transoral robotic surgery (TORS) to otolaryngology practice with the da Vinci Surgical system, we have in our armamentarium a new approach to the BOT. The improved exposure with new retractors, 3-dimensional (3-D) visualization and magnification and advanced motion capacity allow for increased ease to perform surgery in this difficult area. In recent years, several articles published the data about safety and feasibility of TORS for various conditions. This article presents our approach to the BOT for neoplasms including malignant and benign lesions. PMID- 26891533 TI - Transoral robotic surgery for parapharyngeal lesions: a case series of four benign tumours. AB - OBJECTIVES: The parapharyngeal space (PPS) is an anatomically complex space in the vicinity of vital structures. With the introduction of the daVinci robot in head and neck surgery, the surgical robotic system is now being used to gain direct access to the parapharyngeal space and to excise the tumors endoscopically. This study evaluates the outcomes of four patients with benign PPS tumors treated with a transoral robotic surgery approach in a single centre. MATERIAL AND METHODS: All patients with benign tumors of the PPS who underwent transoral resection (between January 2012 and June 2014) using the robot were included in this retrospective study. RESULTS: The study population comprised of two males and two females with a mean age of 52 (range 34-66 years). The parapharyngeal mass was successfully transorally removed in all cases. Overall, mean length of stay was 3.25 days with mean time to oral diet of one day. No intraoperative, perioperative or postoperative complications were encountered. The histological diagnosis was pleomorphic adenoma in two cases (50%). The other two cases were: schwannoma and angioma. There were no recurrences on radiological investigations during a mean follow-up of 14.5 months. MRI scan showed a stable residual fibrotic lesion in case of the angioma. The preoperative complaints of mucus in the throat, painless swelling of the soft palate or throat burden of all patients resolved after surgery. CONCLUSION: With the assistance of the surgical robotic system, benign tumors within the PPS can be excised safely without neck incisions. Further long-term evaluation is needed to define patient selection and the role of TORS for PPS neoplasms. PMID- 26891534 TI - Transaxillary robotic thyroidectomy: Belgian team learning from the first 50 cases. AB - BACKGROUND: In search for less invasive operative techniques, the da Vinci Robot System was introduced in thyroid surgery. Previous studies have reported on safety, effectiveness and improved cosmetics of transaxillary endoscopic thyroidectomy procedures in selected cases. METHODS: We report on the first 50 patients that have been treated with a gasless transaxillary robot-assisted thyroidectomy in a Belgian institution. We describe the implementation, the operative technique and results of robotic thyroid surgery. RESULTS: 48 hemithyroidectomy and 2 total thyroidectomy procedures were performed. The mean ultrasound dimensions of the nodules were 3.4 +/- 1.0 cm (range 1.0-8.0 cm). The mean operative time was significantly longer than with a conventional open approach: 215 min +/- 55 min (range 133 min-347 min). No major complications were observed. All patients were "satisfied" about the cosmetic outcome. CONCLUSION: Transaxillary robotic thyroid surgery is demanding, but feasible. Selected patients can benefit from this technique with an optimal cosmetic outcome. Ideal indication in the hand of our team is a hemithyroidectomy for benign nodules ranging up to 5 cm. PMID- 26891535 TI - Swallowing dysfunction in myotonic dystrophy: a retrospective study of symptomatology and radiographic findings. AB - BACKGROUND: Swallowing dysfunction is a common symptom of myotonic dystrophy, but it is poorly documented in large patient series. This retrospective study was designed to investigate the presence of swallowing symptoms in a large study population and to describe a specific pattern of clinical and radiographic abnormalities. METHODS: A retrospective analysis was made of 169 files of patients with confirmed MD. Neuromuscular assessment was made by means of a standardised neurological examination; clinical swallowing symptoms were listed, and video-fluoroscopic images were analysed. RESULTS: More than half the patients reported swallowing complaints. The major symptoms were frequent choking, difficult pharyngeal transport and piecemeal deglutition. The pharyngeal phase of swallowing was most frequently compromised. This was shown radiographicaly in reduced pharyngeal peristalsis, hypopharyngeal stasis and fragmented swallowing. Aspiration was seen in half of the patients, mostly during swallowing. A typical 'hung position' of the hyoid was also seen. Different onset types of MD seem to be accompanied by comparable subjective complaints and radiographic symptoms. CONCLUSIONS: Pharyngeal transport was most affected in this patient population. Muscular weakness seems to be the major contributor to swallowing impairment in MD. Swallowing abnormalities may be present even if patients report only a few symptoms and even if the severity of the disease is not pronounced. PMID- 26891537 TI - Outcomes in open structure septorhinoplasty. AB - OBJECTIVES: This study assessed the patient-related outcome measures and complications of post-open structure septorhinoplasty. It also investigated the factors associated with the need for revision surgery. METHODS: We prospectively reviewed the case notes of patients who underwent septorhinoplasty performed by a single rhinologist at our institute between August 2011 and August 2013. Patient satisfaction was assessed using the Rhinoplasty Outcomes Evaluation (ROE) tool. RESULTS: A total of 120 patients were included with a mean follow-up time of 28.2 months. Eight patients (6.7%) required revision nasal surgery. There was a significant increase in the mean post-operative ROE score of all patients who underwent surgery (19.5 +/- 9.41 vs. 68.4 +/- 23.7,p < 0.001). The rate of revision surgery was significantly higher in patients with complex surgeries (3/12 vs. 5/108, p = 0.03). There were higher rates of nasal tip deformity surgery and augmentation surgery in the revision surgery group compared to the primary surgery group: 8/17 vs. 20/103, p = 0.03 for nasal tip and 10/17 vs. 27/103, p = 0.01 for augmentation. CONCLUSIONS: Open structure septorhinoplasty significantly increased the ROE score. Our rate of revision surgery, 6.7%, was lower than the average rate of 10%-18% reported in the literature. The rate of revision surgery was higher in cases judged pre-operatively to be more complex. PMID- 26891538 TI - Idiopathic epistaxis and meteorological factors: case-control study. AB - OBJECTIVE: The aim of this study was to determine the relationship between the occurrence of idiopathic epistaxis and daily values of air pressure, temperature, and humidity. We also investigated whether biometeorological forecasts should be addressed to persons with a history of nosebleed diathesis. METHODS: We analyzed consecutive idiopathic epistaxis events over a 3-year period. Patients were included if they had been in the municipality of Mostar, Bosnia and Herzegovina at least 24 hours before the epistaxis occurrence. The monthly variation in epistaxis events was determined. Epistaxis days (Days "0", 0 = day with epistaxis occurrence) and selected nonepistaxis days (Days "-1", -1 = each first single day without epistaxis prior to Day 0) were compared according to daily values of mean, minimum, and maximum temperature; diurnal temperature range; minimum and maximum atmospheric pressure; diurnal pressure range; and mean relative humidity. RESULTS: The greatest and smallest percentage of epistaxis events occurred in the months of March and August, respectively. There were no significant differences between Days 0 and Days -1 with respect to the examined meteorological factors. CONCLUSION: In this region with a Mediterranean climate, we found a seasonal variation with an incidence peak during the spring transition months, but we did not identify any meteorological trigger factors for epistaxis. Thus, there is no need for biometeorological forecasts to be addressed to persons with a history of nosebleed diathesis. PMID- 26891536 TI - Septoplasty is a proven and effective procedure: an expert's view of a burning issue. AB - PROBLEM: The scientific research agenda of the Dutch Association of Otorhinolaryngology and Head & Neck Surgery claims that there is a knowledge gap with regard to the efficacy of septoplasty for a blocked nose. This assertion is based on a restrictive approach to evidence-based medicine that could result in unnecessary trials and the abolition or rationing of sound treatment options. METHODOLOGY: The arguments in favour of the effectiveness of septoplasty are based on the total spectrum of evidence from research, clinical experience and basic science. RESULTS: The best available evidence shows that this form of treatment is satisfactory for more than two thirds of all patients. CONCLUSION: If all levels of evidence are taken into account, it becomes clear that there is no knowledge gap with regard to the efficacy of septoplasty for blocked nose. PMID- 26891539 TI - Tool for assessing surgical tracheostomy skills in otolaryngology residents. AB - OBJECTIVE: The tracheostomy is an essential component of otolaryngology surgery training. There is a pressing need for a reliable, valid, intra-operative assessment tool for assessing the tracheostomy skills of residents in training programs. This study aimed to develop an assessment tool for surgical tracheostomy that was valid, reliable, and feasible. METHODOLOGY: Based on a previously developed tool, the Objective Structured Assessment of Technical Skills, we developed an objective structured tool specifically for assessing tracheostomy skills (OSTS). Our panel included Otorhinolaryngology Head & Neck Surgery faculty members, academic otolaryngologists, and medical education experts. To test the OSTS, 8 board certified otolaryngologists assessed 44 residents from 5-year residency programs in the operating theater, from July 2010 to May 2012, in three tertiary level academic institutions. Residents received constructive feedback after the assessments. RESULTS: The OSTS displayed good reliability, in terms of internal consistency (alpha = 0.761). Its validity was established based on significant improvement in senior resident scores compared to junior resident scores, assessed with an ANOVA (F = 5.31, p = 0.001). The tool also displayed an overall trend of score improvement with an individual's advancement through each year of postgraduate training. The evaluators considered the OSTS easy to understand, complete, practical, and time-efficient, which established its face validity. CONCLUSION: The OSTS is a valid, reliable tool for evaluating surgical competency of residents performing tracheostomy. It provided systematic and comprehensive feedback. The examiners and examinees both displayed positive attitudes towards the instrument. PMID- 26891540 TI - Sialendoscopy learning curve: comparing our first and last 100 procedures. AB - OBJECTIVES: Sialendoscopy is a relatively new minimally invasive technique that permits direct salivary tree visualization and is important in obstructive sialadenitis management and treatment. The present study aimed to examine the sialendoscopy learning curve between March 2009 and March 2013. METHODOLOGY: We compared the first and last 100 sialendoscopies performed in our department with regard to anaesthesia type, operating time, success rate, technical difficulty, major complications, and clinical improvement. RESULTS: General anaesthesia rates were 63% and 38% (P = 0.0004) among the first and last 100 sialendoscopies, respectively. Among the first and last 100 procedures, respectively, average operating times were 39 and 25 minutes (P = 0.00055) for diagnostic sialendoscopies and 68 and 65 minutes (P = 0.35) for interventional sialendoscopies. Successful stone extraction rates were 65% and 90.2% (P = 0.0058) among the first and last 100 procedures, respectively, while the corresponding rates of successful stenosis dilation were 92.5% and 97.1% (P = 0.27). Technical difficulty was encountered in 25% and 17% (P = 0.164) of the first and last 100 sialendoscopies, respectively. Neither group experienced major complications. All patients tolerated the procedures well and had excellent outcomes. CONCLUSION: Progressive learning regarding sialendoscopy enabled more frequent operation under local anaesthesia, thus better meeting the requirements of a minimally invasive technique. We were able to decrease the operative time in diagnostic sialendoscopy. These two factors support the inclusion of diagnostic sialendoscopy into the diagnostic panel in obstructive glandular diseases. PMID- 26891541 TI - Inflammatory pseudotumour of the temporomandibular joint. AB - Head and neck inflammatory pseudotumors (IPs) are rare, idiopathic, non neoplastic lesions that most commonly affect the orbit, but may involve other areas such as the larynx, oropharynx, paranasal sinuses, and meninges. We report the case of a 55-year-old man who presented with progressive left-sided hearing loss, aural fullness, and otalgia. Computed tomography and magnetic resonance imaging (MRI) detected a soft-tissue mass in the left temporomandibular joint (TMJ). Histopathologic examination showed overlying squamous epithelium with hyperkeratosis, parakeratosis, subepithelial fibrosis, and chronic inflammatory infiltrate, which were consistent with an IP. Radiologic images and MRI indicated an ill-defined soft tissue involving the roof and posterior aspect of the TMJ, extending into the anterior external auditory canal. Our case was treated with a 2-week course of high dose prednisone (1 mg/kg) and a 2-week taper with resolution of symptoms. Two years after treatment, the patient shows no evidence of recurrence on MRI. PMID- 26891542 TI - Dutch health-related quality of life measure for chronic otitis media. AB - OBJECTIVE: Chronic otitis media (COM) describes a variety of symptoms and physical findings that result from prolonged damage to the middle ear by infection and inflammation. The Health-Related Quality of Life measure for COM (COMQ-12) is a new questionnaire for the assessment of COM that evaluates the overall burden of disease from the patient's perspective. The aim of this study was to develop and appraise the psychometric properties of the Dutch version of the COMQ-12. MATERIALS AND METHODS: The Dutch version of the COMQ-12 was obtained through translation and back-translation. Fifty adult patients with a history of active COM completed the Dutch version of the COMQ-12. The internal consistency of this questionnaire was evaluated using Cronbach's alpha coefficient. RESULTS: The average COMQ-12 score was 22.4 (SD 11.9). The internal consistency of the Dutch version of the COMQ-12 was high, with a Cronbach's alpha value of 0.833. CONCLUSIONS: The Dutch version of the COMQ-12 provides appropriate health-related quality of life outcome measures in patients with a history of COM. This questionnaire is a useful tool to evaluate the overall burden of disease from the patient's perspective. PMID- 26891543 TI - Slight conductive hearing loss in children with narrowed maxilla and deep palatal vault. AB - PROBLEM/OBJECTIVES: Maxillary constriction and high palatal arch are associated with increased risk of chronic eustachian tube dysfunction and conductive hearing loss (CHL) due to chronic effusion. However, this relationship has not been clearly demonstrated. This study assessed CHL in school children with a narrowed maxilla and deep palatal vault. METHODOLOGY: Thirty-two children with maxillary constriction were randomly selected for the study group and 28 children with normal transverse maxillary development were selected for the control group. Pure tone audiograms were obtained for all children, and hearing levels and air-bone gaps were measured. RESULTS: Air-bone gap measurements in the control group ranged from 5.50 to 14.50 decibels (dB), and in the study group they were between 5.00 and 24.00 dB. In the study group, 14 (43.8%) children had slight CHL, and the remaining 18 (56.2%) children had normal hearing levels. In the control group, all of the children had normal hearing levels. Hearing levels and air-bone gaps were greater in the study group than the control group. CONCLUSION: This study showed that children with a narrowed maxilla and deep palatal vault may have slight CHL. Therefore, the onset of CHL should be followed with hearing screening programs. PMID- 26891544 TI - Incidence of congenital CMV in children at a hearing rehabilitation center. AB - OBJECTIVE: To evaluate the incidence of children with congenital CMV (cCMV) infection in a hearing rehabilitation center. METHODOLOGY: This was a retrospective review of 309 children followed in a rehabilitation center for mild to total sensorineural hearing loss (SNHL). Seventy-five children had dried blood spots that we retrieved and retrospectively analyzed for the presence of CMV DNA by real time PCR. The children were born in Belgium after January 1996. The etiology of the SNHL was investigated for each child. RESULTS: The CMV DNA was detected in the dried blood spots for 8 of the 75 children tested (10.6%) by real time PCR. In three children, an alternative etiology of SNHL was suspected before the cCMV infection was diagnosed. CONCLUSIONS: The incidence of children infected with cCMV in a hearing rehabilitation center is high (10.6%). The detection of CMV DNA in dried blood spots is useful and improves the etiological diagnosis of SNHL. PMID- 26891545 TI - Incidental findings of a Vestibular Schwannoma on Brain MRI. AB - Brain magnetic resonance imaging (MRI) is the gold standard for diagnosing a vestibular schwannoma (VS). The prevalence of VS ranges from 0.02-2.4%; the incidence is 20 per million per year. This case report describes two cases of VS identified on brain MRIs that were not related to the purpose of the MRI examination. A literature search was performed to find existing audiometric-based protocols for guiding MRI referrals. Asymmetric sensorineural hearing loss appeared to be the most important indication for excluding VS. However, no consensus was found on the significance of asymmetry or on the severity required to exclude VS. In light of the current absence of a reliable audiometric-based protocol for MRI referral, it seems reasonable to refer every patient with audiovestibular symptoms for a brain MRI, despite the view that the low number of incidental findings may not justify the additional cost. PMID- 26891546 TI - Congenital laryngeal cyst: an unusual cause of stridor in the neonate. AB - BACKGROUND: Congenital laryngeal cysts are a rare, but potentially fatal, cause of airway obstruction in infants and children. Most laryngeal cysts are acquired. Here, we describe a congenital laryngeal cyst, its treatment, and its presentation immediately after birth. CASE REPORT: A newborn child developed stridor very shortly after birth, due to a large, congenital saccular cyst. The diagnosis was based on a laryngoscopy and imaging studies, which detected an extralaryngeal extension through the cricothyroid membrane. The cyst was removed with an endoscopic procedure and a CO2-laser. Afterwards, the cyst recurred, but was successfully removed with an external approach. CONCLUSION: Clinical manifestations of laryngeal cysts in neonates shortly after birth are rare. Here, we present an interesting clinical case. We also concisely reviewed the literature on the epidemiology, clinical presentation, diagnosis, classification, and therapy for laryngeal cysts. PMID- 26891547 TI - Case report: Endoscopic endonasal removal of large osteoma in the ethmoid sinus. AB - PROBLEM: A 25-year-old man presented with a large osteoma in the right ethmoidal sinus. METHODOLOGY: The osteoma was removed by an endoscopic endonasal approach with a curved diamond drill and an electromagnetic navigation system. RESULT: Computed tomography 3 days after surgery showed complete removal of the osteoma and normal position of the right eyeball. No long-term follow-up results were available. CONCLUSIONS: This clinical case highlights the use of the endoscopic endonasal approach for the safe and reliable treatment of sinus osteomas, particularly large osteomas. We also describe various manifestations of osteoma, its diagnosis, and surgical management. PMID- 26891548 TI - Enzyme Therapy: Current Perspectives. AB - Enzymes control all metabolic processes in human system from simple digestion of food to highly complex immune response. Physiological reactions occuring in healthy individuals are disturbed when enzymes are deficient or absent. Enzymes are administered for normalizing biological function in certain pathologies. Initially, crude proteolytic enzymes were used for the treatment of gastrointestinal disorders. Recent advances have enabled enzyme therapy as a promising tool in the treatment of cardiovascular, oncological and hereditary diseases. Now, a spectrum of other diseases are also covered under enzyme therapy. But, the available information on the use of enzymes as therapeutic agents for different diseases is scanty. This review details the enzymes which have been used to treat various diseases/disorders. PMID- 26891549 TI - Testicular cytology indicates differences in Sertoli cell counts between "good freezer" and "poor freezer" bulls. AB - In artificial insemination, poor quality of semen unsuitable for cryopreservation and susceptibility of spermatozoa to cryodamage in crossbred bulls have been a matter of concern. Present study was designed to identify the testicular cytology indices that might be used to predict the semen quality and cryotolerance of spermatozoa in bulls. Based on the ejaculate rejection rate and sperm cryotolerance, bulls (Holstein Friesian X Tharparkar crossbred) were classified into either good (producing good quality semen with spermatozoa having good cryotolerance; n = 4) or poor (producing poor quality semen with spermatozoa having poor cryotolerance; n = 4). Testicular cytology was studied in all the 8 bulls using fine needle aspiration technique. Testicular cytology of good bulls and poor bulls differed significantly. The proportion of Sertoli cells was significantly higher in good bulls (25.3 +/- 1.6) compared to poor bulls (11.0 +/ 0.8). The Sertoli cell index was 46.1 +/- 5.0 in good bulls while it was only 13.8 +/- 1.3 in poor bulls. The cut off values, as determined using Receiver Operating Characteristics analysis, indicate that the bulls having testicular cytogram comprising of < 15.5% Sertoli cells, < 24.3 Sertoli cell index and > 4.0 spermatogenic cells to Sertoli cell ratio might be a poor bull in terms of semen quality and cryotolerance of spermatozoa. The proportion of Sertoli cells in the testicular cytology had positive (P < 0.05) relationship with semen quality and cryotolerance of spermatozoa. PMID- 26891550 TI - Cloning and characterization of a water deficit stress responsive transcription factor gene from Oryza sativa L. AB - Understanding the biochemical and molecular basis of drought mechanism in rice is important as drought is one of the major causes affecting rice crop adversely. A 1017 bp gene sequence encoding AP2/ERF family TF was isolated from Oryza sativa sp. Indica cv N22 encoding a protein of 338 amino acid residues, with a molecular weight of 36.58 kDa, and no intron in the ORF. The gene was named as AP2/ERF N22(2) different from the drought responsive gene AP2/ERF-N22 that we reported earlier. AP2/ERF-N22(2) has entirely different characteristics from that of AP2/ERF-N22. It has a single AP2 domain of 55 amino acid residues and a cluster of acidic amino acid residues at the C-terminal region, which could function as a trans-activation domain. Presence of NLS indicates that it is a nuclear localized transcription factor encoding gene. It falls in group VI L, sharing characteristic similarities. Arabidopsis members of group VI L have been shown to be involved in response to cytokinin under drought stress. PMID- 26891551 TI - Potential of Vigna radiata (L.) sprouts in the management of inflammation and arthritis in rats: Possible biochemical alterations. AB - Vigna radiata (Fabaceae) is an important pulse crop widespread throughout the tropics and warm temperature regions. In this study, we evaluated the in vitro anti-inflammatory and in vivo antiarthritic activity of Vigna radiata sprouts in rats. The in vitro anti-inflammatory activity was determined by membrane stabilization and protein denaturation method. Whereas, the antiarthritic activity of the ethanolic extract of the sprouts was evaluated by complete Freund's adjuvant model with diclofenac sodium as the standard drug. Body weights, paw volume, biochemical parameters such as lipid peroxidation, total reduced glutathione, myeloperoxidase and lysosomal enzymes like cathepsin-D, N acetyl beta-D-glucosamindase and beta-D-glucuronidase were estimated. Treatment with ethanolic extract of V. radiata exhibited significant membrane stabilization activity and protein denaturation activity, and significantly attenuated the biochemical changes induced by administration of complete Freund's adjuvant. The findings of the present study suggest the possible role of Vigna radiata in the therapeutics of arthritis. PMID- 26891552 TI - Protective role of diet supplements Spirulina and Tamarind fruit pulp on kidney in sodium fluoride exposed Swiss albino mice: Histological and biochemical indices. AB - Fluoride toxicity through potable water, particularly ground water, is not uncommon in countries such as India, China, Iran, Iraq, Turkey, parts of Africa and Afghanistan. Kidney being the main organ involved in fluoride removal, it accumulates considerable amount of fluoride. Here, we report toxic effects of oral exposure of Swiss albino mice to fluoride (sub-acute: 190 mg/kg body wt. for 7 days; and sub-chronic: 94 mg/kg body wt. for 90 days) and recovery of sub chronic fluoride exposed mice after 90 days of sodium fluoride (NaF) withdrawal. The role of diet supplements (Spirulina and tamarind fruit pulp @ 230 mg/kg body wt. independently as well as in combination) in amelioration of fluoride toxicity has also been screened. Compared with controls, feed intake decreased from 3-43%, body wt. 4-18%, and kidney wt. 5-12% in treated mice (except diet supplement groups of sub-chronic exposure) while their water intake increased from 4-43%. Histopathological changes in the cortical region of kidney in fluoride treated mice were as follows: dilation of bowman's capsule and thickening of its parietal and visceral layer; alterations in glomeruli size and their sclerotization; increase in bowman's space; proliferation of mesangial cells; reduction in podocyte counts; and dilation of proximal and distal tubules. Fluoride exposure altered tissue biochemistry (protein, acid phosphatase and alkaline phosphatase content) and increased urea (23-58%) and creatinine content (14-127%) in the serum. Sub-acute exposure was found more toxic. The diet modulation not only reduced fluoride toxicity but also led to better recovery of treated mice after withdrawal, especially in combination. PMID- 26891553 TI - Effect of sweetener and flavoring agent on oxidative indices, liver and kidney function levels in rats. AB - Food additives while attract consumers, improve quality, control weight and replace sugar, may affect seriously children and adults health. Here, we investigated the adverse effects of saccharin and methylsalicyltaes as sweetener and flavoring agent on lipid profile, blood glucose, renal, hepatic function and oxidative stress/antioxidants (lipid peroxidation, catalase and reduced glutathione in liver tissues). Saccharin and methylsalicylate were administered orally in young male albino rats at low and high dose for 30 days. Rats were divided into 5 groups, 1st control group, 2nd and 3rd (low and high saccharin treated groups) and 4th and 5th (low and high methylsalicylate-treated group). Serum total cholesterol, triglyceride, glucose levels and body weight gain were found decreased in saccharin high dose group compared to control. Rats consumed high dose of saccharin showed a significant decrease in serum triglycerides, cholesterol and LDL levels. Low and high doses of saccharin exhibited a significant increase in liver function marker of ALT, AST, ALP activity, total proteins and albumin levels and renal function test (urea and creatinine levels) in comparison with control group. Further, saccharin at high dose induced significant decrease in liver GSH levels, catalase and SOD activity and increase in hepatic MDA level. Overall saccharin harmfully altered biochemical markers in liver and kidney at higher as well as lower doses. Whereas, methyl salicylates did not pose a risk for renal function and hepatic oxidative markers. PMID- 26891555 TI - Production of alpha-galactosidase from Aspergillus foetidus MTCC 6322 by solid state fermentation and its application in soymilk hydrolysis. AB - The production of alpha-galactosidase from the wild fungal strain Aspergillus foetidus MTCC 6322 using solid state fermentation (SSF), its characterization, and its efficacy in the hydrolysis of soymilk using response surface methodology were studied. The optimum conditions for production of alpha-galactosidase by SSF were: wheat bran (10 g), moisture content (64%), inoculum volume (1.0 mL; 6 x 10(7) spores/mL) with a yield of 4.1 x 10(3) units per gram dry substrate (U/gds) at 96 h. The enzyme showed optimum activity at 6.0, temperature 40 degrees C, pH stability between 5.0-8.0, and temperature stability between 30-40 degrees C. The enzyme was stable in the presence of trypsin, lipase, and collagenase and it showed susceptibility of the substrates such as raffinose, melibiose, guar gum and soymilk to hydrolysis in varying degrees. The optimized conditions for soymilk hydrolysis were: soymilk (10 mL) from defatted soybean meal (1.5%), alpha galactosidase (0.15 UmL(-1) at 30 degrees C, pH 6.0 and duration of 1 h. PMID- 26891554 TI - Purification and characterization of chitinase from Streptomyces violascens NRRL B2700. AB - Chitinase is one of the important enzymes as it is directly linked to Chitin that has wide applications in industrial, medical and commercial fields for its biocompatibility and biodegradability. Here, we report extracellular chitinase production by Streptomyces violascens NRRL B2700 under submerged fermentation condition. Chitinase production started after 10 h of incubation and reached to maximum level at 72 h of cultivation. Studies on the influence of additional carbon and nitrogen sources on chitinase production revealed that maltose, xylose, fructose, lactose, soybean meal and ammonium nitrate served as good carbon and nitrogen sources to enhance chitinase yield by 1.6 to 6 fold. Medium supplemented with 1% colloidal chitin produced high chitinase concentration (0.1714 U/mg). The enzyme chitinase was purified from the culture broth by 75% ammonium sulphate precipitation, DEAE-cellulose ion-exchange and sephadex G-100 gel filtration. The molecular mass of the purified chitinase was 65 kDa as estimated by SDS-PAGE. The apparent Michaelis constant (K(m)) and the maximum rate (V(max)) of the enzyme for colloidal chitin were 1.556 mg/mL and 2.680 MUM/min/mg, respectively suggested high affinity towards-chitin. Possibly, it is the first report on production of chitinase from S. violascens NRRL B2700. The findings were encouraging, especially for cost effective production, and further warrants media and purification optimization studies for enhanced yield. PMID- 26891556 TI - The Documented Past and the Exciting Future. PMID- 26891557 TI - Clinical Perspectives in Compounding: Compounding Gains and Losses Since I Met "Careless arithmetic nullifies careful compounding". PMID- 26891558 TI - International Academy of Compounding Pharmacists' Legislative Regulatory Update: Take Action! Stop the U.S. Food and Drug Administration's Misguided Veterinary Guidance. PMID- 26891559 TI - Applying Quality by Design Concepts to Pharmacy Compounding. AB - Compounding of medications is an important part of the practice of the pharmacy profession. Because compounded medications do not have U.S. Food and Drug Administration approval, a pharmacist has the responsibility to ensure that compounded medications are of suitable quality, safety, and efficacy. The Federal Government and numerous states have updated their laws and regulations regarding pharmacy compounding as a result of recent quality issues. Compounding pharmacists are expected to follow good preparation prodecures in their compounding practices in much the same way pharmaceutical manufacturers are required to follow Current Good Manufacturing Procedures as detailed in the United States Code of Federal Regulations. Application of Quality by Design concepts to the preparation process for a compounded medication can help in understanding the potential pitfalls and the means to mitigate their impact. The goal is to build quality into the compounding process to ensure that the resultant compounded prescription meets the human or animal patients' requirements. PMID- 26891560 TI - Root Cause Analysis, Part 1: Nonsterile Compounding. AB - When an adverse event or near miss occurs in a pharmacy, eliminating the root cause to prevent recurrence is critically important. We occasionally see pharmacies address deviations in a manner that only superficially addresses the adverse event, but does not address the root cause of the problem, thereby putting patients and the pharmacy at risk of a recurrence. This article proposes a method for performing Root Cause Analysis. PMID- 26891562 TI - Mixing In a Compounding Pharmacy in the 21st Century. AB - When it comes to combining ingredients for topical preparations, compounding pharmacists utilize either the manual methods such as a spatula and pill tile or a mortar and pestle, typically an electronic mortar and pestle. If a topical preparation must be pre-ground or requires trituration, or any level of particle size reduction, historically the manual method of combining ingredients in such a preparation would include the initial use of a mortar and pestle; however with micronized substances this is not as much a concern today as in the past. There is, of course, the concern of a lack of reproducibility, knowing that each compounder might utilize the equipment differently, would mix for varying times, and would also mix with varying amounts of physical pressure applied to the pestle. If the discipline of uniform usage is great enough in the lab, this method could probably produce consistent results, but, because of the preparation and cleanup time and the fact that newer technology is available, this method is not recommended as the common compounding method in a compounding pharmacy that does more than a handful of compounded topical preparations per week. This article is not meant to say these methods are not appropriate, but, rather, to point out that newer technology is available and might be preferable in order to provide a cleaner, more efficient, and more reproducible lab environment. PMID- 26891561 TI - Basic Principles of Lyophilization, Part 1. AB - The achievement of a high-quality lyophilized (freeze-dried) dosage form involves the combination of optimal formulation design and optimal freeze-dry cycle design. This 2-part article describes how this can be done. Part 1 discusses the basic principles and procedures of lyophilization up to a discussion on the different stages of lyophilization. The stages of lyophilization are discussed in part 2. PMID- 26891563 TI - U.S. Food and Drug Administration. "Evaluation Criteria" for Difficult to Compound Drugs. AB - This is part 2 of a 2-part article on the topic of Nominations of Difficult to Compound Drugs to the FDA-PCAC. Part 1 provided a current list of Nominations of Difficult to Compound Drugs to the FDA-PCAC. This article discusses the evaluation procedure for determining which drugs are demonstrably difficult to compound. PMID- 26891564 TI - Sterile Product Packaging and Delivery Systems. AB - Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology. PMID- 26891565 TI - Pharmacists' Perceptions of the Economic Value of Compounded Pharmaceuticals: A Comparison of Compounded and Commercial Pharmaceuticals in Select Disease States. AB - Studies have been conducted to assess patient satisfaction with compounded pharmaceuticals and to directly compare compounded pharmaceuticals with their comparable commercial pharmaceuticals. Yet, the economic value of or potential for economic value derived from compounded pharmaceuticals relative to commercial pharmaceuticals is still not known. Therefore, the purpose of this study was to assess and compare compounding and non-compounding pharmacists' perceptions of the economic value of compounded preparations relative to commercial products. In depth interviews with 10 compounding pharmacists and physicians who prescribe compounded prescription pharmaceutical preparations were conducted to help develop a self-administered questionnaire distributed to 50 compounding and 50 non-compounding pharmacists. Compounding and non-compounding pharmacists' perceptions differed most often in the context of compounded pharmaceuticals for pediatric patients. However, both groups responded with moderate agreement that compounded prescription treatments are more profitable for the pharmacy than commercial prescription treatments in most therapeutic areas. This research sought to understand the perception of pharmacists of areas for potential direct and indirect economic cost savings as a result of compounding. For all items whereby compounding and non-compounding pharmacists' ratings were significantly different, compounding pharmacists more strongly believed that compounding pharmaceuticals offered benefit and vice versa. The differences in ratings that were most common were those that directly compared the economic value of compounding and commercial pharmaceuticals, with compounding pharmacists more strongly agreeing with the potential cost savings associated with compounded pharmaceuticals. Based on these findings, prescription compounds are believed to have a benefit to the health system by those who provide them. Future research should proactively explore the economic benefit of compounded preparations compared to conventionally manufactured products to determine the economic value of compounded pharmaceuticals for patients, pharmacies, physicians, and the healthcare system. PMID- 26891567 TI - Pharmacy Fellowship Program: Building a Stronger Profession. PMID- 26891566 TI - Long-term Stability of Esomeprazole in 5% Dextrose Infusion Polyolefin Bags at 5 degrees C +/- 3 degrees C after Microwave Freeze-thaw Treatment. AB - To improve quality assurance, security, time management, and cost saving of drug delivery, preparation in advance of intravenous solutions has been developed for several infusion solutions. The objective of this study was to investigate the stability of esomeprazole 0.4 mg/mL and 0.8 mg/mL in 5% dextrose polyolefin bags after freezing, long-term storage, and microwave thawing. The stability of five polyolefin bags containing approximately 0.4 mg/mL of esomeprazole and five other bags containing approximately 0.8 mg/mL in 5% dextrose prepared under aseptic conditions was studied after freezing for 1 month at -20 degrees C, thawing in a microwave oven with a validated cycle, and stored at 5 degrees C +/- 3 degrees C. Esomeprazole concentration was measured by high-pressure liquid chromatography using a reversed-phase column C8, a mobile phase consisting of 35% of acetonitrile and 65% of Na2HPO4 buffer at pH 7.59 with HPO4 (2 M) and NaOH (0.5 M), and detection with a diode array detector at 280 nm. Visual, microscopic, and spectrophotometric observation and pH measurements were also performed. No precipitation occurred in the preparations but little change of color was observed. No microaggregate was observed with optical microscopy or revealed by a change of absorbance at 350, 410, and 550 nm. Based on a shelf life of 90% residual potency, esomeprazole solutions (0.4 and 0.8 mg/mL) were stable for at least 20 or 29 days, respectively, after a freezing and microwave thawing period, where 95% one-side lower confidence limit of the concentration-time profile remained superior to 90% of the initial concentration. During this period, the pH values of drug solutions have been observed to decrease without affecting chromatographic parameters. Within these limits, esomeprazole (0.4 and 0.8 mg/mL) in 5% dextrose infusions may be prepared and frozen in advance by a centralized intravenous admixture service, thawed, and stored at least 20 days at 5 degrees C +/- 3 degrees C before use in clinical units. PMID- 26891568 TI - [#practiceforms]. PMID- 26891569 TI - [Equinella: Most important results from the evaluation of the pilot phase 2014 2015]. PMID- 26891570 TI - [Calling into question the tax-free financial profit made by the purchase of businesses]. PMID- 26891571 TI - [50 years of Swine Health Service (SGD)]. PMID- 26891572 TI - [Lung and pleural lesions before and after implementation of a national eradication program against enzootic pneumonia and actinobacillosis as well as changes of slaughter carcass organs in slaughter pigs in Switzerland]. AB - In a representative cross-sectional study during 12 months of the years 2008/2009 in four abattoirs in Switzerland, lung and pleura lesions as well as lesions of slaughter carcasses and organs of 34 706 pigs were studied for frequency and type of macroscopic lesions. Of the 24276 examined pigs, 91.2% of the lungs, 94.4% of the heart and 95.5% of the livers showed no macroscopically visible lesions. Pigs that were produced for a label program had significantly less bronchopneumonia and pneumonia residuals, pleuritis and liver lesions due to echinococcosis. Pigs supervised by the Swiss Pig Health Service (SGD), showed significantly less bronchopneumonia and pneumonia residuals, diffuse pleuritis, pleuritis/pericarditis and milkspots compared to the non-SGD supervised farms. Thanks to the national eradication program for enzootic pneumonia (EP) and actinobacillosis, the health-status of lungs has been considerably improved and the prevalence of pleurisy decreased considerably. The results of this study indicate a good herd health in Swiss pig production. PMID- 26891573 TI - [Influence of personal attitude of the manager on antibiotic use in pig production]. AB - The attitude as well as the expertise of a person affect the behavior and actions in daily life. To investigate the influence of attitude and knowledge of pig producers on the use of antibiotics in farms, 220 Swiss pig producers were questioned on health awareness, attitude towards sustainable production, risk behavior, intrinsic motivation and knowledge about antibiotics and resistance development. In addition, the strategy of antibiotic use (therapeutic or prophylactic) and the business practice (single or group therapy) for the amount of antibiotics on one hand and for the risk of antibiotic resistance development on the other hand, were determined in a personal interview. Farmers using antibiotics only therapeutically had a better business practice. A direct link between the personal attitude and the antibiotic use or a higher risk of development of antibiotic resistance was not found in this investigation. PMID- 26891574 TI - [Risk factors for the oral use of antibiotics and animal treatment incidence of weaners in Switzerland]. AB - In the present study, risk factors for the use of oral antibiotics in weaned piglets were collected on 112 pig farms by a personal questionaire. The most common indication for an antibiotic group therapy was diarrhoea, and the most frequently used antibiotic was Colistin. On average, 27.33 daily doses in the control farms and 387.21 daily doses in the problem farms per 1000 weaners were administered on a given day. The significant risk factors in the multivariate model were poor hygiene in the water supply of suckling piglets, less than two doses ofprestarter feed daily, lack of an all-in-and-all-out production system in weaners, no herd book performance data analysis, and less than two of the legally prescribed veterinary visits per year. Furthermore, the treatment incidence of weaners for oral antibiotics was calculated on the basis of the drug inventory. This study provides evidence that the use of oral antibiotics in weaners can be reduced by interventions in hygiene and management. PMID- 26891576 TI - IMPACT OF MORNING STIFFNESS, EDUCATION, AND AGE ON THE FUNCTIONAL STATUS OF PATIENTS WITH RHEUMATOID ARTHRITIS. AB - The purpose of this study was to explore the relationship between disability status and duration of morning stiffness in hands with regard to age, level of education, and gender in patients with rheumatoid arthritis (RA). Also, the authors wanted to investigate this relationship with regard to the presence of rheumatoid factor, i.e., the serological status. A retrospective study was conducted in 250 patients with the classic form of RA (186 females, s64 males, mean age Xb = 49.96 y ears, range 25-60 years, disease duration 1-27 years, Xb = 6.41) previously diagnosed with RA according to the ACR (American College of Rheumatology 1987 criteria). All patients were in Steinbrocker functional classes II and III. The probability level was expressed by p < 0.01 and p < 0.05. The relationship between the variables was measured by point-biserial correlation. The correlation between duration of morning stiffness and functional class was positive but low [(r = 0.10, y = 0.00x + 2.37, p > 0.05) seronegative, (r = 0.12, y = 0.00x + 2.30, p > 0.05) seropositive]. High positive values were obtained for the linear correlation coefficient between duration of the disease and functional class (p < 0.01). Also, high values were obtained regarding the coefficient of correlation between age and functional class [(r = 0.29, p < 0.01) seronegative, (r = 0.47, p < 0.01) seropositive]. Uneducated patients were significantly more represented in functional class III [ 23 (50%) seronegative, 19 (42.2%) seropositive] than in functional class II [16 (20.3%) seronegative, 22 (27.5%) seropositive]. In conclusion, in this study of patients with rheumatoid arthritis, increased duration of morning stiffness was associated with functional disability. Functional disability increased with the duration of the disease, depended on age and educational level, and was more pronounced in older age, regardless of RA serological status. With regard to serological status and sex, the differences were non-significant. PMID- 26891575 TI - [Evaluation of risk factors for Mastitis-Metritis-Agalactia in pig farms in Switzerland]. AB - Mastitis-Metritis-Agalactia (MMA), also known as postpartum dysgalactia syndrome (PPDS) is the most important disease complex in sows after birth. The present study compared 30 MMA problem herds (over 12% of farrowing sows affected) with 30 control farms (less than 10% of farrowing sows affected) to identify risk factors and treatment incidence. Important risk factors identified were in gilts the integration into the herd after the first farrowing, in gestating sows firm fecal consistency as well as in lactating sows soiled troughs, a low flow rate (<2 liters per minute) in drinking nipples and a high prevalence of lameness. The treatment incidence was also significantly different between the two groups. The MMA prevalence could be reduced through optimization of husbandry, feeding and management, which could essentially diminish the use of antibiotics. PMID- 26891579 TI - [Not Available]. PMID- 26891577 TI - [PATHOGENESIS OF UNDIFFERENTIATED SPONDYLOARTHRITIS]. AB - Spondyloarthritis or spondyloarthropathy (SpA) is a multifactorial disease in which a disturbed interplay occurs between the immune system and environmental factors on a predisposing genetic background, which leads to inflammation and structural damage of target tissue. Many recent researches on development of SpA showed important role of innate and adaptive immunity as well as of prominent bone tissue remodeling which leads to osteoproliferation and ankylosis. It is believed that possible sites of inflammation in SpA are entheses, sinovium and gut. Current knowledge on inflammation and tissue destruction leads to conclusion that SpA is disease characterized by disorders on different levels. Disorder on the first level is disturbed pathogen recognition and immune response activation, on second level disturbed inflammatory cells migration and on third level disturbed immune response regulation. As follows, disease progress depends on range of disturbances: disease course can be short, as in reactive arthritis, or long-lasting with substantial structural damage, as in ankylosing spondylitis. Unfortunately, there are still no confident markers of disease progression, so at the mere beginning disease is often described as undifferentiated. PMID- 26891578 TI - [CRYOGLOBULINEMICVASCULITIS AS A MANIFESTATION OF PARANEOPLASTIC SYNDROME--A CASE REPORT]. AB - Cryoglobulinemia refers to the presence of circulating cryoglobulins in the serum which may lead to organ damage and systemic response characterized by fatigue, arthralgias, purpura, glomerulonephritis and neuropathy. The disease mainly affects small and medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Mixed cryoglobulinemia (type I and II) are most often associated with infections, especially hepatitis C virus (HCV), but may occur as part of lymphoproliferative and autoimmune diseases. We present a 75-year-old male patient with acrocyanosis and digital necrosis of the left hand and purpura of the lower extremities. Since 2001 the patient was treated for Non-Hodgkin's lymphoma of the stomach (MALT) and since 2002 for Sjogren's syndrome. Extensive diagnostic procedures revealed cryoglobulinemia type II, but without evidence of HCV infection or relapse of lymphoproliferative disorder. Furthermore, poorly differentiated prostate adenocarcinoma was diagnosed and antiandrogen treatment was initiated. One year after the onset of symptoms acrocyanosis and digital necrosis, gastric adenocarcinoma was diagnosed, without metastatic disease, and surgical treatment was performed. However, postoperatively recurrence of new digital necrosis of the hands occurred along with clinical deterioration and multiple organ failure leading to lethal outcome. Association of cryoglobulinemia and solid tumors is rarely described in the literature, so it is very important to perform comprehensive diagnostic evaluation and detect potential underlying disease as soon as possible. PMID- 26891580 TI - [Not Available]. PMID- 26891581 TI - [Not Available]. PMID- 26891583 TI - [Not Available]. PMID- 26891582 TI - [Not Available]. PMID- 26891584 TI - [Not Available]. PMID- 26891585 TI - [Not Available]. PMID- 26891586 TI - [Not Available]. PMID- 26891587 TI - [Not Available]. PMID- 26891588 TI - miR-17-92 plays an oncogenic role and conveys chemo-resistance to cisplatin in human prostate cancer cells. AB - The mir-17-92 cluster consists of six mature miRNAs and is implicated in diverse human cancers by targeting mRNAs involved in distinct pathways that either promote or inhibit carcinogenesis. However, the molecular mechanism underlying the mir-17-92 cluster-mediated pro-tumorigenic or anti-tumorigenic effects has not been clearly elucidated in prostate cancer. In the present study, the role of the mir-17-92 cluster in diverse aspects of prostate cancer cells has been thoroughly investigated. Forced introduction of the mir-17-92 cluster into the androgen-independent DU145 prostate cancer cells evidently promoted cell growth due to disruption of the balance between cellular proliferation and apoptosis. Overexpression of the mir-17-92 cluster significantly improved the migration and invasion of the DU145 cells, attributed to the induction of integrin beta-1. Notably, the mir-17-92 cluster conveyed chemo-resistance to cisplatin. We demonstrated that the mir-17-92 cluster suppressed the expression of inhibitor of the AKT signaling pathway and activated the AKT pathway subsequently, which played a central role in regulating cellular proliferation, apoptosis and chemo resistance. Continuously activated ERK1/2 signaling also contributed importantly to these processes. The present study provides key evidence for crucial oncogenic role of the miR-17-92 cluster in prostate cancer cells. Further investigations are warranted to determine whether miR-17-92 cluster can be targeted for future treatment of human prostate cancer. PMID- 26891589 TI - Root growth restraint can be an acclimatory response to low pH and is associated with reduced cell mortality: a possible role of class III peroxidases and NADPH oxidases. AB - Low pH (<5.0) can significantly decrease root growth but whether this is a direct effect of H(+) or an active plant response is examined here. Tomato (Solanum lycopersicum cv Micro-Tom) roots were exposed directly or gradually to low pH through step-wise changes in pH over periods ranging from 4 to 24 h. Roots exposed gradually to pH 4.5 grew even less than those exposed directly, indicating a plant-coordinated response. Direct exposure to pH 4.0 suppressed root growth and caused high cell mortality, in contrast to roots exposed gradually, in which growth remained inhibited but cell viability was maintained. Total class III peroxidase activity increased significantly in all low pH treatments, but was not correlated with the observed differential responses. Use of the enzyme inhibitors salicylhydroxamic acid (SHAM) or diphenyleneiodonium chloride (DPI) suggest that peroxidase and, to a lesser extent, NADPH oxidase were required to prevent or reduce injury in all low pH treatments. However, a role for other enzymes, such as the alternative oxidase is also possible. The results with SHAM, but not DPI, were confirmed in tobacco BY-2 cells. Our results indicate that root growth inhibition from low pH can be part of an active plant response, and suggest that peroxidases may have a critical early role in reducing loss of cell viability and in the observed root growth constraint. PMID- 26891590 TI - Synthesis and application of a nanoporous ion-imprinted polymer for the separation and preconcentration of trace amounts of vanadium from food samples before determination by electrothermal atomic absorption spectrometry. AB - A vanadium ion-imprinted polymer was synthesized in the presence of V(V) and N benzoyl-N-phenyl hydroxyl amine using 4-vinyl pyridine as the monomer, ethylene glycol dimethacrylate as the cross linker and 2,2'-azobis(isobutyronitrile) as the initiator. The imprinted V(V) ions were completely removed by leaching the polymer with 5 mol/L nitric acid, and the polymer structure was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The ion imprinted polymer was used as the sorbent in the development of the solid-phase extraction method for V(V) prior to its determination by electrothermal atomic absorption spectrometry. The maximum sorption capacity for V(V) ions was 26.7 mg/g at pH 4.0. Under the optimum conditions, for a sample volume of 150.0 mL, an enrichment factor of 289.0 and a detection limit of 6.4 ng/L were obtained. The developed method was successfully applied to the determination of vanadium in parsley, zucchini, black tea, rice, and water samples. PMID- 26891591 TI - Antiatherogenic effects of ellagic acid and urolithins in vitro. AB - Atherosclerosis, one of the leading causes of death worldwide, is characterized by impaired endothelial function and lipid metabolism, among other factors. Ellagitannins are a class of phenolic compounds that may play a role in cardiovascular health. This work aimed to study the potential atheroprotective effects of urolithins, ellagitannin-derived gut microbiota metabolites, on different key factors in atherosclerosis development: the ability of monocytes to adhere to endothelial cells and the uptake and efflux of cholesterol by macrophages. The biotransformations urolithins undergo in peripheral cells were also evaluated. Results indicated that some urolithins and ellagic acid were able to reduce the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the secretion of a cellular adhesion molecule (sVCAM-1) and pro-inflammatory cytokine (IL-6). Urolithin C, a combination of urolithins A and B, and ellagic acid also decreased the accumulation of cholesterol in THP-1 derived macrophages, but they were not able to promote cholesterol efflux. The analysis of cell media by UHPLC-ESI-MS(n) indicated urolithins and ellagic underwent extensive metabolism, with sulfate and methyl conjugation. This evidence indicates that atherosclerotic processes may be attenuated by urolithins, but future human intervention trials are required to establish if is translated in vivo. PMID- 26891593 TI - Boron nitride nanotubes as vehicles for intracellular delivery of fluorescent drugs and probes. AB - AIM: To evaluate the response of cells to boron nitride nanotubes (BNNTs) carrying fluorescent probes or drugs in their inner channel by assessment of the cellular localization of the fluorescent cargo, evaluation of the in vitro release and biological activity of a drug (curcumin) loaded in BNNTs. METHODS: Cells treated with curcumin-loaded BNNTs and stimulated with lipopolysaccharide were assessed for nitric oxide release and stimulation of IL-6 and TNF-alpha. The cellular trafficking of two cell-permeant dyes and a non-cell-permeant dye loaded within BNNTs was imaged. RESULTS: BNNTs loaded with up to 13 wt% fluorophores were internalized by cells and controlled release of curcumin triggered cellular pathways associated with the known anti-inflammatory effects of the drug. CONCLUSION: The overall findings indicate that BNNTs can function as nanocarriers of biologically relevant probes/drugs allowing one to examine/control their local intracellular localization and biochemical effects, leading the way to applications as intracellular nanosensors. PMID- 26891594 TI - Using optimal combination of teaching-learning methods (open book assignment and group tutorials) as revision exercises to improve learning outcome in low achievers in biochemistry. AB - Graduate medical students of India are taught Biochemistry by didactic lectures and they hardly get any opportunity to clarify their doubts and reinforce the concepts which they learn in these lectures. We used a combination of teaching learning (T-L) methods (open book assignment followed by group tutorials) to study their efficacy in improving the learning outcome. About 143 graduate medical students were classified into low (<50%: group 1, n = 23), medium (50 75%: group 2, n = 74), and high (>75%: group 3, n = 46) achievers, based on their internal assessment marks. After the regular teaching module on the topics "Vitamins and Enzymology", all the students attempted an open book assignment without peer consultation. Then all the students participated in group tutorials. The effects on the groups were evaluated by pre and posttests at the end of each phase, with the same set of MCQs. Gain from group tutorials and overall gain was significantly higher in the low achievers, compared to other groups. High and medium achievers obtained more gain from open book assignment, than group tutorials. The overall gain was significantly higher than the gain obtained from open book assignment or group tutorials, in all three groups. All the three groups retained the gain even after 1 week of the exercise. Hence, optimal use of novel T-L methods (open book assignment followed by group tutorials) as revision exercises help in strengthening concepts in Biochemistry in this oft neglected group of low achievers in graduate medical education. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):321-325, 2016. PMID- 26891595 TI - Low-energy, Mobile Grain Boundaries in Magnesium. AB - The strong basal texture that is commonly developed during the rolling of magnesium alloy and can even increase during annealing motivates atomic-level study of dislocation structures of both <0001> tilt and twist grain boundaries (GBs) in Magnesium. Both symmetrical tilt and twist GBs over the entire range of rotation angles theta between 0 degrees and 60 degrees are found to have an ordered atomic structure and can be described with grain boundary dislocation models. In particular, 30 degrees tilt and twist GBs are corresponding to energy minima. The 30 degrees tilt GB is characterized with an array of Shockley partial dislocations bp:-bp on every basal plane and the 30 degrees twist GB is characterized with a stacking faulted structure. More interesting, molecular dynamics simulations explored that both 30 degrees tilt and twist GBs are highly mobile associated with collective glide of Shockley partial dislocations. This could be responsible for the formation of the strong basal texture and a significant number of 30 degrees misorientation GBs in Mg alloy during grain growth. PMID- 26891597 TI - Relationship between choroidal thickness and visual impairment in multiple evanescent white dot syndrome. PMID- 26891592 TI - Structural determinants of muscle thin filament cooperativity. AB - End-to-end connections between adjacent tropomyosin molecules along the muscle thin filament allow long-range conformational rearrangement of the multicomponent filament structure. This process is influenced by Ca(2+) and the troponin regulatory complexes, as well as by myosin crossbridge heads that bind to and activate the filament. Access of myosin crossbridges onto actin is gated by tropomyosin, and in the case of striated muscle filaments, troponin acts as a gatekeeper. The resulting tropomyosin-troponin-myosin on-off switching mechanism that controls muscle contractility is a complex cooperative and dynamic system with highly nonlinear behavior. Here, we review key information that leads us to view tropomyosin as central to the communication pathway that coordinates the multifaceted effectors that modulate and tune striated muscle contraction. We posit that an understanding of this communication pathway provides a framework for more in-depth mechanistic characterization of myopathy-associated mutational perturbations currently under investigation by many research groups. PMID- 26891598 TI - An efficient synthesis of iminoquinones by a chemoselective domino ortho hydroxylation/oxidation/imidation sequence of 2-aminoaryl ketones. AB - An efficient chemoselective domino oxidative homocoupling of 2-aminoaryl ketones in the presence of 2-iodoxybenzoic acid (IBX) for the synthesis of iminoquinone has been developed. The domino reaction proceeds via three consecutive steps, such as domino ortho-hydroxylation of 2-aminoaryl ketones, oxidation of a phenol derivative to benzoquinone and dimerization through imine formation to yield iminoquinone. Importantly, this reaction allows the recycling of the oxidant IBX by recovering the by-product iodosobenzoic acid (IBA) and oxidizing it back to IBX. A four step domino strategy for the synthesis of iminoquinone through in situ generation of 2-amino benzophenone from (2-amino phenyl)(phenyl)methanol was also developed. PMID- 26891596 TI - Update: Influenza Activity--United States, October 4, 2015-February 6, 2016. AB - From October through mid-December 2015, influenza activity remained low in most regions of the United States. Activity began to increase in late December 2015 and continued to increase slowly through early February 2016. Influenza A viruses have been most frequently identified, with influenza A (H3N2) viruses predominating during October until early December, and influenza A (H1N1)pdm09 viruses predominating from mid-December until early February. Most of the influenza viruses characterized during that time are antigenically similar to vaccine virus strains recommended for inclusion in the 2015-16 Northern Hemisphere vaccines. This report summarizes U.S. influenza activity* during October 4, 2015-February 6, 2016, and updates the previous summary (1). PMID- 26891599 TI - Structural effects of simvastatin on liver rat [corrected] tissue: Fourier transform infrared and Raman microspectroscopic studies. AB - Simvastatin is one of the most frequently prescribed statins because of its efficacy in the treatment of hypercholesterolemia, reducing cardiovascular risk and related mortality. Determination of its side effects on different tissues is mandatory to improve safe use of this drug. In the present study, the effects of simvastatin on molecular composition and structure of healthy rat livers were investigated by Fourier transform infrared and Raman imaging. Simvastatin-treated groups received 50 mg/kg/day simvastatin for 30 days. The ratio of the area and/or intensity of the bands assigned to lipids, proteins, and nucleic acids were calculated to get information about the drug-induced changes in tissues. Loss of unsaturation, accumulation of end products of lipid peroxidation, and alterations in lipid-to-protein ratio were observed in the treated group. Protein secondary structure studies revealed significant decrease in alpha-helix and increase in random coil, while native beta-sheet decreases and aggregated beta sheet increases in treated group implying simvastatin-induced protein denaturation. Moreover, groups were successfully discriminated using principal component analysis. Consequently, high-dose simvastatin treatment induces hepatic lipid peroxidation and changes in molecular content and protein secondary structure, implying the risk of liver disorders in drug therapy. PMID- 26891600 TI - Quantitative performance characterization of three-dimensional noncontact fluorescence molecular tomography. AB - Fluorescent proteins and dyes are routine tools for biological research to describe the behavior of genes, proteins, and cells, as well as more complex physiological dynamics such as vessel permeability and pharmacokinetics. The use of these probes in whole body in vivo imaging would allow extending the range and scope of current biomedical applications and would be of great interest. In order to comply with a wide variety of application demands, in vivo imaging platform requirements span from wide spectral coverage to precise quantification capabilities. Fluorescence molecular tomography (FMT) detects and reconstructs in three dimensions the distribution of a fluorophore in vivo. Noncontact FMT allows fast scanning of an excitation source and noninvasive measurement of emitted fluorescent light using a virtual array detector operating in free space. Here, a rigorous process is defined that fully characterizes the performance of a custom built horizontal noncontact FMT setup. Dynamic range, sensitivity, and quantitative accuracy across the visible spectrum were evaluated using fluorophores with emissions between 520 and 660 nm. These results demonstrate that high-performance quantitative three-dimensional visible light FMT allowed the detection of challenging mesenteric lymph nodes in vivo and the comparison of spectrally distinct fluorescent reporters in cell culture. PMID- 26891601 TI - Reflective Fourier ptychography. AB - The Fourier ptychography technique in reflection mode has great potential applications in tissue imaging and optical inspection, but the current configuration either has a limitation on cut-off frequency or is not practical. By placing the imaging aperture stop outside the illumination path, the illumination numerical aperture (NA) can be greater than the imaging NA of the objective lens. Thus, the cut-off frequency achieved in the proposed optical system is greater than twice the objective's NA divided by the wavelength (2NAobj/lambda ), which is the diffraction limit for the cut-off frequency in an incoherent epi-illumination configuration. We experimentally demonstrated that the synthesized NA is increased by a factor of 4.5 using the proposed optical concept. The key advantage of the proposed system is that it can achieve high resolution imaging over a large field of view with a simple objective. It will have a great potential for applications in endoscopy, biomedical imaging, surface metrology, and industrial inspection. PMID- 26891603 TI - Competence-sensitive outcomes. PMID- 26891602 TI - Current state and future prospects of research on fear of cancer recurrence. AB - Despite a rapidly growing research interest in fear of cancer recurrence, lack of consensus on definition and measurement including clinical fear of cancer recurrence, sparse model development and testing, and limited available clinical interventions have impeded knowledge transfer into patient services. To move forward, a 2-day colloquium was held in Ottawa, Canada in August 2015 to progress knowledge and identify future research directions. A comprehensive research program was proposed, including development of a clinical definition, an updated review of screening measures, and a review of existing interventions. A new special interest group was created with the International Psychosocial Oncology Society to facilitate the implementation of this research program and future international collaborations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891604 TI - Concordance of Advance Care Plans With Inpatient Directives in the Electronic Medical Record for Older Patients Admitted From the Emergency Department. AB - CONTEXT: Measuring What Matters identified quality indicators to examine the percentage of patients with documentation of a surrogate decision maker and preferences for life-sustaining treatments. OBJECTIVES: To determine the rate of advance care planning in older adults presenting to the emergency department (ED) and translation into medical directives in the electronic medical record (EMR). METHODS: A convenience sample of adults 65 years or older was recruited from a large urban ED beginning in January 2012. We administered a baseline interview and survey in English or Spanish, including questions about whether patients had a documented health care proxy or living will. For patients admitted to the hospital who had a health care proxy or living will, chart abstraction was performed to determine whether their advance care preferences were documented in the EMR. RESULTS: From February 2012 to May 2013, 53.8% (367 of 682) of older adults who completed the survey in the ED reported having a health care proxy, and 40.2% (274 of 682) had a living will. Of those admitted to the hospital, only 4% (4 of 94) of patients who said they had a living will had medical directives documented in the EMR. Similarly, only 4% (5 of 115) of patients who had a health care proxy had the person's name or contact information documented in their medical record. CONCLUSION: About half of the patients 65 years or older arriving in the ED have done significant advance care planning, but most plans are not recorded in the EMR. PMID- 26891605 TI - Living With an Older Person Dying From Cancer, Lung Disease, or Dementia: Health Outcomes From a General Practice Cohort Study. AB - CONTEXT: Increasing numbers of people will die from chronic disease. Families contribute significantly to end-of-life care, but their role may not be recognized. OBJECTIVES: To 1) establish the proportion of older cohabitees identified in primary care as "carers"; 2) describe demographic and lifestyle characteristics of cohabitees of people terminally ill with cancer, dementia, and chronic obstructive pulmonary disease (COPD); 3) describe their health a year before and after bereavement; and 4) compare health outcomes between cohabitees of people dying with cancer, COPD, or dementia. METHODS: Retrospective cohort study using a U.K. primary care database (The Health Improvement Network) of 13,693 bereaved cohabitees (a proxy marker for being a carer), aged 60 years or older of people dying from cancer, COPD, or dementia. Characteristics were described one year before and after bereavement. We compared cancer, COPD, and dementia cohabitee outcomes using incidence rate ratios one year before and after bereavement and calculated mortality risk after bereavement. RESULTS: A total of 6.9% of cohabitees were recorded as carers. Health outcomes differed little between the three groups of cohabitees in the year before or after bereavement. The proportion of cohabitees with six or more consultations increased the year after bereavement (cancer cohabitees 16.0% to 18.8%, COPD cohabitees 17.8% to 20.4%, and dementia cohabitees 15.5% to 17.5%). At postbereavement (follow-up median 3 years, interquartile range 1.3-5.4), we found no mortality differences between the three groups. CONCLUSION: Recording of carers of terminally ill people was suboptimal. Cause of bereavement produced few differential effects on health outcomes or mortality. PMID- 26891606 TI - Anticipatory Nausea, Risk Factors, and Its Impact on Chemotherapy-Induced Nausea and Vomiting: Results From the Pan European Emesis Registry Study. AB - CONTEXT: Anticipatory (prechemotherapy) nausea (AN) is a classic conditioned symptom not responding well to current antiemetics. Minimal work has been done to assess its risk factors and impact on chemotherapy-induced nausea and vomiting (CINV). OBJECTIVES: To evaluate risk factors for AN and assess its impact on CINV development. METHODS: We analyzed data (n = 991) from a prospective observational multisite study in eight European countries over three cycles of chemotherapy. Patient/treatment characteristics were collected before chemotherapy. History of nausea/vomiting (yes/no), patient expectation of CINV (0-100 mm visual analog scale, [VAS]), and prechemotherapy anxiety (0-100 mm VAS) also were collected before chemotherapy. A patient-completed diary during each chemotherapy cycle obtained information on AN in the 24 hours before chemotherapy administration and nausea and vomiting (episodes of vomiting and severity of nausea) daily for five days after administration of chemotherapy (0-100 mm VAS). RESULTS: AN was reported by 8.3%-13.8% of patients, increasing in frequency and intensity over each cycle. Every 1 mm increase in AN on the VAS was significantly associated with 2%-13% of increase in the likelihood of CINV (all P-values <0.05). Key predictors of AN in Cycle 1 included metastatic disease and prechemotherapy anxiety. However, predictors of AN in subsequent cycles included prechemotherapy anxiety and AN and CINV experience in the previous cycle, the latter being the strongest predictor (odds ratio = 3.30-4.09 for CINV outcomes over the cycles). CONCLUSION: AN is a challenging symptom, and its prevention needs to consider better CINV prevention in the previous cycles as well as managing prechemotherapy anxiety. PMID- 26891607 TI - Prospective Study of Patient-Reported Symptom Burden in Patients With Non-Small Cell Lung Cancer Undergoing Proton or Photon Chemoradiation Therapy. AB - CONTEXT: Intensity-modulated radiation therapy (IMRT), three-dimensional conformal radiation therapy (3DCRT), and proton-beam therapy (PBT) are chemoradiotherapy modalities for treating locally advanced non-small-cell lung cancer. Although therapy is carefully planned to maximize treatment benefit while minimizing risk for adverse side effects, most patients develop radiation-induced symptom burden. OBJECTIVES: To demonstrate the MD Anderson Symptom Inventory's ability to detect fine differences in symptom development among these modalities. METHODS: This was a longitudinal observational study. Patients with unresectable primary or recurrent non-small-cell lung cancer (n = 82) underwent 3DCRT, IMRT, or PBT. Patients rated MD Anderson Symptom Inventory symptoms weekly for up to 12 weeks. We used mixed-effect modeling to estimate development of symptoms and functional interference. RESULTS: The PBT group received a significantly higher radiation target dose than did the IMRT and 3DCRT groups (P < 0.001). Fatigue was the most severe symptom over time for all groups. Controlling for patient and clinical factors (age, sex, race, cancer stage, performance status, body mass index, previous cancer therapy, total radiation dose), we found that pain, as a major esophagitis-related symptom, increased more during therapy (P = 0.019) and decreased more after (P = 0.013) therapy in the 3DCRT and IMRT groups than in the PBT group. Compared with the PBT group, the 3DCRT and IMRT groups reported greater decrease in systemic symptoms (fatigue, drowsiness, lack of appetite, disturbed sleep) after therapy (P = 0.016). CONCLUSION: Patients receiving PBT reported significantly less severe symptoms than did patients receiving IMRT or 3DCRT. These results should be confirmed in a randomized study with comparable tumor burden among therapies. PMID- 26891610 TI - Attitudes Among Patients With Advanced Cancer Toward Euthanasia and Living Wills. PMID- 26891608 TI - Role of the Nasogastric Tube and Lingzhi (Ganoderma lucidum) in Palliative Care. AB - Decision-making on behalf of an incapacitated patient at the end of life is a complex process, particularly in family-centric societies. The situation is more complex when attempts are made to accommodate Eastern concepts of end-of-life care with more conventional Western approaches. In this case report of an incapacitated 74-year-old Singaporean man of Malay descent with relapsed Stage 4 diffuse large B cell lymphoma who was without an established lasting power of attorney, we highlight the difficult deliberations that ensue when the patient's family, acting as his proxy, elected to administer lingzhi through his nasogastric tube (NGT). Focusing on the questions pertaining to end-of-life decision-making in Asia, we consider the issues surrounding the use of NGT and lingzhi in palliative care (PC) and the implementation of NGT for administering lingzhi in a PC setting, particularly in light of a dearth of data on such treatment measures among PC patients. PMID- 26891609 TI - Complementary and Alternative Medicine Approaches for Pain in Underserved Chinese American Cancer Patients: Prevalence and Correlates. PMID- 26891611 TI - Saw Palmetto for Symptom Management During Radiation Therapy for Prostate Cancer. AB - CONTEXT: Lower urinary tract symptoms (LUTSs) affect 75%-80% of men undergoing radiation therapy (RT) for prostate cancer. OBJECTIVES: To determine the safety, maximum tolerated dose (MTD), and preliminary efficacy of Serenoa repens commonly known as saw palmetto (SP) for management of LUTS during RT for prostate cancer. METHODS: The dose finding phase used the time-to-event continual reassessment method to evaluate safety of three doses (320, 640, and 960 mg) of SP. Dose limiting toxicities were assessed for 22 weeks using the Common Terminology Criteria for Adverse Events for nausea, gastritis, and anorexia. The exploratory randomized controlled trial phase assessed preliminary efficacy of the MTD against placebo. The primary outcome of LUTS was measured over 22 weeks using the International Prostate Symptom Score. Additional longitudinal assessments included quality of life measured with the Functional Assessment of Cancer Therapy-Prostate. RESULTS: The dose finding phase was completed by 27 men who reported no dose-limiting toxicities and with 20 participants at the MTD of 960 mg daily. The exploratory randomized controlled trial phase included 21 men, and no statistically significant differences in the International Prostate Symptom Score were observed. The prostate-specific concerns score of the Functional Assessment of Cancer Therapy-Prostate improved in the SP group (P = 0.03). Of 11 men in the placebo group, two received physician-prescribed medications to manage LUTS compared with none of the 10 men in the SP group. CONCLUSION: SP at 960 mg may be a safe herbal supplement, but its efficacy in managing LUTS during RT needs further investigation. PMID- 26891612 TI - How recent advances in molecular tests could impact the diagnosis of pneumonia. AB - Molecular diagnostic tests have been the single major development in pneumonia diagnostics over recent years. Nucleic acid detection tests (NATs) have greatly improved the ability to detect respiratory viruses and bacterial pathogens that do not normally colonize the respiratory tract. In contrast, NATs do not yet have an established role for diagnosing pneumonia caused by bacteria that commonly colonize the nasopharynx due to difficulties discriminating between pathogens and coincidental carriage strains. New approaches are needed to distinguish infection from colonization, such as through use of quantitative methods and identification of discriminating cut-off levels. The recent realization that the lung microbiome exists has provided new insights into the pathogenesis of pneumonia involving the interaction between multiple microorganisms. New developments in molecular diagnostics must account for this new paradigm. PMID- 26891613 TI - Cell Density and Joint microRNA-133a and microRNA-696 Inhibition Enhance Differentiation and Contractile Function of Engineered Human Skeletal Muscle Tissues. AB - To utilize three-dimensional (3D) engineered human skeletal muscle tissue for translational studies and in vitro studies of drug toxicity, there is a need to promote differentiation and functional behavior. In this study, we identified conditions to promote contraction of engineered human skeletal muscle bundles and examined the effects of transient inhibition of microRNAs (miRs) on myogenic differentiation and function of two-dimensional (2D) and 3D cultures of human myotubes. In 2D cultures, simultaneously inhibiting both miR-133a, which promotes myoblast proliferation, and miR-696, which represses oxidative metabolism, resulted in an increase in sarcomeric alpha-actinin protein and the metabolic coactivator PGC-1alpha protein compared to transfection with a scrambled miR sequence (negative control). Although PGC-1alpha was elevated following joint inhibition of miRs 133a and 696, there was no difference in myosin heavy chain (MHC) protein isoforms. 3D engineered human skeletal muscle myobundles seeded with 5 * 10(6) human skeletal myoblasts (HSkM)/mL and cultured for 2 weeks after onset of differentiation consistently did not contract when stimulated electrically, whereas those seeded with myoblasts at 10 * 10(6) HSkM/mL or higher did contract. When HSkM were transfected with both anti-miRs and seeded into fibrin hydrogels and cultured for 2 weeks under static conditions, twitch and tetanic specific forces after electrical stimulation were greater than for myobundles prepared with HSkM transfected with scrambled sequences. Immunofluorescence and Western blots of 3D myobundles indicate that anti-miR-133a or anti-miR-696 treatment led to modest increases in slow MHC, but no consistent increase in fast MHC. Similar to results in 2D, only myobundles prepared with myoblasts treated with anti-miR-133a and anti-miR-696 produced an increase in PGC 1alpha mRNA. PGC-1alpha targets were differentially affected by the treatment. HIF-2alpha mRNA showed an expression pattern similar to that of PGC-1alpha mRNA, but COXII mRNA levels were not affected by the anti-miRs. Overall, joint inhibition of miR-133a and miR-696 accelerated differentiation, elevated the metabolic coactivator PGC-1alpha, and increased the contractile force in 3D engineered human skeletal muscle bundles. PMID- 26891614 TI - Inflammation and immunity in organ regeneration. AB - The ability of vertebrates to regenerate amputated appendages is increasingly well-understood at the cellular level. Cells mediating an innate immune response and inflammation in the injured tissues are a prominent feature of the limb prior to formation of a regeneration blastema, with macrophage activity necessary for blastema growth and successful development of the new limb. Studies involving either anti-inflammatory or pro-inflammatory agents suggest that the local inflammation produced by injury and its timely resolution are both important for regeneration, with blastema patterning inhibited in the presence of unresolved inflammation. Various experiments with Xenopus larvae at stages where regenerative competence is declining show improved digit formation after treatment with certain immunosuppressive, anti-inflammatory, or antioxidant agents. Similar work with the larval Xenopus tail has implicated adaptive immunity with regenerative competence and suggests a requirement for regulatory T cells in regeneration, which also occurs in many systems of tissue regeneration. Recent analyses of the human nail organ indicate a capacity for local immune tolerance, suggesting roles for adaptive immunity in the capacity for mammalian appendage regeneration. New information and better understanding regarding the neuroendocrine-immune axis in the response to stressors, including amputation, suggest additional approaches useful for investigating effects of the immune system during repair and regeneration. PMID- 26891615 TI - Negligible elongation of mucin glycans with Gal beta1-3 units distinguishes the laminated layer of Echinococcus multilocularis from that of Echinococcus granulosus. AB - The larval stages of the cestodes Echinococcus multilocularis and Echinococcus granulosus cause the important zoonoses known as larval echinococcoses. These larvae are protected by a unique, massive, mucin-based structure known as the laminated layer. The mucin glycans of the E. granulosus laminated layer are core 1- or core 2-based O-glycans in which the core Galpbeta1-3 residue can initiate a chain comprising one to three additional Galpbeta1-3 residues, a motif not known in mammalian carbohydrates. This chain can be capped with a Galpalpha1-4 residue, and can be ramified with GlcNAcpbeta1-6 residues. These, as well as the GlcNAcpbeta1-6 residue in core 2, can be decorated with the Galpalpha1-4Galpbeta1 4 disaccharide. Here we extend our analysis to the laminated layer of E. multilocularis, showing that the non-decorated cores, together with Galpbeta1 3(Galpalpha1-4Galpbeta1-4GlcNAcpbeta1-6)GalNAc, comprise over 96% of the glycans in molar terms. This simple laminated layer glycome is exhibited by E. multilocularis grown either in vitro or in vivo. Interestingly, all the differences with the complex laminated layer glycome found in E. granulosus may be explained in terms of strongly reduced activity in E. multilocularis of a putative glycosyltransferase catalysing the elongation with Galpbeta1-3. Comparative inter-species analysis of available genomic and transcriptomic data suggested a candidate for this enzyme, amongst more than 20 putative (non-core 1) Gal/GlcNAc beta1-3 transferases present in each species as a result of a taeniid specific gene expansion. The candidate gene was experimentally verified to be transcribed at much higher levels in the larva of E. granulosus than that of E. multilocularis. PMID- 26891617 TI - Editorial: Editors are Not Publication Police. PMID- 26891616 TI - Selection of highly efficient sgRNAs for CRISPR/Cas9-based plant genome editing. AB - The CRISPR/Cas9-sgRNA system has been developed to mediate genome editing and become a powerful tool for biological research. Employing the CRISPR/Cas9-sgRNA system for genome editing and manipulation has accelerated research and expanded researchers' ability to generate genetic models. However, the method evaluating the efficiency of sgRNAs is lacking in plants. Based on the nucleotide compositions and secondary structures of sgRNAs which have been experimentally validated in plants, we instituted criteria to design efficient sgRNAs. To facilitate the assembly of multiple sgRNA cassettes, we also developed a new strategy to rapidly construct CRISPR/Cas9-sgRNA system for multiplex editing in plants. In theory, up to ten single guide RNA (sgRNA) cassettes can be simultaneously assembled into the final binary vectors. As a proof of concept, 21 sgRNAs complying with the criteria were designed and the corresponding Cas9/sgRNAs expression vectors were constructed. Sequencing analysis of transgenic rice plants suggested that 82% of the desired target sites were edited with deletion, insertion, substitution, and inversion, displaying high editing efficiency. This work provides a convenient approach to select efficient sgRNAs for target editing. PMID- 26891618 TI - Self-adhesive Luting of Partial Ceramic Crowns: Selective Enamel Etching Leads to Higher Survival after 6.5 Years In Vivo. AB - PURPOSE: To investigate the influence of selective enamel etching on long-term clinical performance of partial ceramic crowns (PCCs) luted with a self-adhesive luting material (RXU: RelyX Unicem). MATERIALS AND METHODS: At baseline, 34 patients received the intended treatment: two PCCs (Vita Mark II; Cerec 3D) for the restoration of extended lesions with multiple-cusp coverage were placed in a split-mouth design with a self-adhesive luting material, one without (RXU) and one with selective enamel etching (RXU+E). Patients were evaluated clinically (modified USPHS criteria) at baseline and up to 6.5 years (70 to 88 months). The chi-square test was used for statistical analyses (alpha=0.05). Clinical survival of all restorations (n=68) after 6.5 years was evaluated by Kaplan-Meier analysis. RESULTS: After 6.5 years, 18 patients (9 male, 9 female; median age 41, range 25 to 59 years) with 36 RXU and RXU+E restorations were available for clinical assessment (patient recall rate: 53%), with 13 RXU and 14 RXU+E PCCs placed in molars and 5 RXU and 4 RXU+E PCCs in premolars. Clinically, no statistically significant differences between the luting procedures were detected. Both RXU and RXU+E revealed significant changes over time with respect to marginal adaptation (significant deterioration) and marginal discoloration (significant increase). RXU revealed no cases of postoperative hypersensitivity and RXU+E only did so at baseline (n=5). Kaplan-Meier analysis showed a cumulative survival for RXU of 60% and for RXU+E of 82%, indicating a significantly higher survival rate for RXU+E. CONCLUSION: Clinically, RXU and RXU+E perform similarly. In PCC restorations with multiple-cusp coverage, lack of retention due to adhesive preparation, and little dentin available for adhesion caused by extensive core buildups or cavity linings, selective enamel etching is recommended. PMID- 26891620 TI - Surface Conditioning and Bonding Protocol for Nanocomposite Indirect Restorations: How and Why? PMID- 26891621 TI - STRENGTHENING THE REFLECTIVE FUNCTIONING CAPACITIES OF PARENTS WHO HAVE A CHILD WITH A NEURODEVELOPMENTAL DISABILITY THROUGH A BRIEF, RELATIONSHIP-FOCUSED INTERVENTION. AB - This randomized controlled trial examined the reflective functioning capacities of caregivers who have a child with a neurodevelopmental disorder between the ages of 2 years 0 months and 6 years 11 months. Children with a neurodevelopmental disorder receive a range of diagnoses, including sutism; however, they all exhibit social communication challenges that can derail social relationships. Forty parent-child dyads in Barbados were randomly assigned to either a developmental individual-difference, relationship based/floortime(DIR/FT) group (n = 20), or a psychoeducational (wait-list) group (n = 20) with parental reflective functioning measured before and after a 12-week DIR/FT treatment intervention. Results revealed significant gains in parental reflective functioning in the treatment group, as compared to the psychoeducational (wait-list) group, after the 12-week relationship-focused intervention. PMID- 26891623 TI - Clinical research for older adults in rural areas: the MINDED study experience. AB - Due to the growing need to make clinical decisions based on valid and objective scientific evidence, the number of randomized controlled trials (RCTs) has increased over the last three decades. Nevertheless, evidence-based medicine has still limited applicability in older adults, because they are often excluded from clinical trials. Evidence-based medicine is even more challenging in rural areas, as its remote environment provides additional barriers. Nevertheless, given the high prevalence of older adults living in rural settings, research in this type of environment has become crucial. This can only be accomplished by considering the multiple additional challenges of these regions. In this paper, we examine potential environmental, procedural, and participants' barriers to the management of a RCT in a rural area. Possible solutions and suggestions are provided based on our experience-from the Multidomain Intervention to preveNt Disability in ElDers (MINDED) project. PMID- 26891622 TI - A DNA aptamer recognising a malaria protein biomarker can function as part of a DNA origami assembly. AB - DNA aptamers have potential for disease diagnosis and as therapeutics, particularly when interfaced with programmable molecular technology. Here we have combined DNA aptamers specific for the malaria biomarker Plasmodium falciparum lactate dehydrogenase (PfLDH) with a DNA origami scaffold. Twelve aptamers that recognise PfLDH were integrated into a rectangular DNA origami and atomic force microscopy demonstrated that the incorporated aptamers preserve their ability to specifically bind target protein. Captured PfLDH retained enzymatic activity and protein-aptamer binding was observed dynamically using high-speed AFM. This work demonstrates the ability of DNA aptamers to recognise a malaria biomarker whilst being integrated within a supramolecular DNA scaffold, opening new possibilities for malaria diagnostic approaches based on DNA nanotechnology. PMID- 26891624 TI - Solitary Wave in One-dimensional Buckyball System at Nanoscale. AB - We have studied the stress wave propagation in one-dimensional (1-D) nanoscopic buckyball (C60) system by molecular dynamics (MD) simulation and quantitative modeling. Simulation results have shown that solitary waves are generated and propagating in the buckyball system through impacting one buckyball at one end of the buckyball chain. We have found the solitary wave behaviors are closely dependent on the initial temperature and impacting speed of the buckyball chain. There are almost no dispersion and dissipation of the solitary waves (stationary solitary wave) for relatively low temperature and high impacting speed. While for relatively high temperature and low impacting speed the profile of the solitary waves is highly distorted and dissipated after propagating several tens of buckyballs. A phase diagram is proposed to describe the effect of the temperature and impacting speed on the solitary wave behaviors in buckyball system. In order to quantitatively describe the wave behavior in buckyball system, a simple nonlinear-spring model is established, which can describe the MD simulation results at low temperature very well. The results presented in this work may lay a solid step towards the further understanding and manipulation of stress wave propagation and impact energy mitigation at nanoscale. PMID- 26891625 TI - Vicarious trial and error. AB - When rats come to a decision point, they sometimes pause and look back and forth as if deliberating over the choice; at other times, they proceed as if they have already made their decision. In the 1930s, this pause-and-look behaviour was termed 'vicarious trial and error' (VTE), with the implication that the rat was 'thinking about the future'. The discovery in 2007 that the firing of hippocampal place cells gives rise to alternating representations of each of the potential path options in a serial manner during VTE suggested a possible neural mechanism that could underlie the representations of future outcomes. More-recent experiments examining VTE in rats suggest that there are direct parallels to human processes of deliberative decision making, working memory and mental time travel. PMID- 26891627 TI - Stroke vision, aphasia, neglect (VAN) assessment-a novel emergent large vessel occlusion screening tool: pilot study and comparison with current clinical severity indices. AB - BACKGROUND: Identification of emergent large vessel occlusion (ELVO) stroke has become increasingly important with the recent publications of favorable acute stroke thrombectomy trials. Multiple screening tools exist but the length of the examination and the false positive rate range from good to adequate. A screening tool was designed and tested in the emergency department using nurse responders without a scoring system. METHODS: The vision, aphasia, and neglect (VAN) screening tool was designed to quickly assess functional neurovascular anatomy. While objective, there is no need to calculate or score with VAN. After training participating nurses to use it, VAN was used as an ELVO screen for all stroke patients on arrival to our emergency room before physician evaluation and CT scan. RESULTS: There were 62 consecutive code stroke activations during the pilot study. 19 (31%) of the patients were VAN positive and 24 (39%) had a National Institutes of Health Stroke Scale (NIHSS) score of >=6. All 14 patients with ELVO were either VAN positive or assigned a NIHSS score >=6. While both clinical severity thresholds had 100% sensitivity, VAN was more specific (90% vs 74% for NIHSS >=6). Similarly, while VAN and NIHSS >=6 had 100% negative predictive value, VAN had a 74% positive predictive value while NIHSS >=6 had only a 58% positive predictive value. CONCLUSIONS: The VAN screening tool accurately identified ELVO patients and outperformed a NIHSS >=6 severity threshold and may best allow clinical teams to expedite care and mobilize resources for ELVO patients. A larger study to both validate this screening tool and compare with others is warranted. PMID- 26891626 TI - Extracellular vesicles round off communication in the nervous system. AB - Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system. PMID- 26891630 TI - 20 years of JBMT - Changes and continuity. PMID- 26891628 TI - L1CAM Expression is Related to Non-Endometrioid Histology, and Prognostic for Poor Outcome in Endometrioid Endometrial Carcinoma. AB - The majority of endometrial carcinomas are classified as Type I endometrioid endometrial carcinomas (EECs) and have a good prognosis. Type II non-endometrioid endometrial carcinomas (NEECs) have a significant worse outcome. Yet, 20 % of the EECs are associated with an unexplained poor outcome. The aim of this study was to determine if L1CAM expression, a recently reported biomarker for aggressive tumor behavior in endometrial carcinoma, was associated with clinicopathological features of EECs. A total of 103 patients diagnosed as EEC at the Radboud University Medical Centre, based on the pathology report were selected. L1CAM status of these tumors was determined, and histologic slides were reviewed by two expert pathologists. L1CAM-positivity was observed in 17 % (18/103). Review of the diagnostic slides revealed that 11 out of these 18 L1CAM-positive tumors (61 %) contained a serous- or mixed carcinoma component that was not initially mentioned in the pathology report. L1CAM-expression was associated with advanced age, poor tumor grade, and lymphovascular space invasion. A worse five year progression free survival rate was observed for patients with L1CAM-positive tumors (55.6 % for the L1CAM-positive group, compared to 83.3 % for the L1CAM negative group P = 0.01). L1CAM expression carries prognostic value for histologically classified EEC and supports the identification of tumors with a NEEC component. PMID- 26891629 TI - In vitro fermentation of alginate and its derivatives by human gut microbiota. AB - Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health. PMID- 26891633 TI - Effects of unilateral posteroanterior mobilization in subjects with sacralized lumbosacral transitional vertebrae. AB - AIM OF THE STUDY: To find out the efficacy of unilateral posteroanterior (PA) mobilization over type IA and type IIA sacralized lumbosacral transitional vertebrae in patients with low back pain with or without leg pain. RESEARCH DESIGN: experimental randomized control study. SAMPLE SIZE: 30 subjects, SAMPLING: simple random sampling. GROUP A - 15 subjects - self lumbar mobility and stretching exercises + Unilateral PA mobilization + hot pack. GROUP B - 15 subjects - self lumbar mobility and stretching exercises + hot pack. Before initiating treatment, subjects were assessed for dependent variables: Pain intensity by VAS, Forward bending and side bending ROM by modified finger to floor method with the help of an inch-tape and functions by Modified Oswestry Functional Disability Questionnaires. Post test measurements were taken after completion 2 weeks of therapy. The results of the study suggest that unilateral PA pressure is an effective mobilization method in reducing low back pain, improving ROM and related disability as compared to impairment based exercises alone in patients with low back pain with or without radiation to lower limbs having abnormally large transverse processes and hypomobile type IA and IIA lumbo sacral transitional vertebrae. PMID- 26891631 TI - Muscle timing in injured and non-injured leg of athletes with chronic ankle instability in response to a visual stimulus during forward jumping. AB - OBJECTIVE: The aim of this study was to investigate premotor time, motor time and reaction time of the injured and non-injured leg muscles of athletes with chronic ankle instability in response to a visual stimulus during forward jumping. METHODS: Surface electromyography was performed on injured and non-injured leg of eight athletes with chronic ankle instability during forward jumping. RESULTS: Results showed that premotor time of the peroneus longus was significantly longer in non-injured leg compared with injured leg (489.37 +/- 220.22 ms vs. 306.46 +/- 142.92 ms, P = 0.031); on the contrary, motor time of the peroneus longus was significantly shorter in non-injured leg compared with injured leg (569.04 +/- 318.62 ms vs. 715.12 +/- 328.72 ms, P = 0.022). No significant difference was noted in the timing of other calf muscles (P > 0.05). CONCLUSION: According to the results of this study, rehabilitation protocols, regarding ankle instability, need to put greater emphasis on tasks that require proper timing of muscles and muscle re-education so that protocols could reduce residual symptoms after sprain and prevent recurrent sprains. PMID- 26891632 TI - Training for improved neuro-muscular control of balance in middle aged females. AB - This study examined improvements in static balance and muscle electromyographic (EMG) activity following a four week progressive training program in 16 middle aged females (mean age = 46.9 +/- 8.7 yrs; height 161.1 +/- 6.0 cm; weight 65.4 +/- 11.2 kg). Participants trained 3 times per week for 4 weeks, for 50 min per session, progressing base of support, stability, vision, resistance and torque in each of six basic exercises. Pre and post training measures of balance included feet together standing, a tandem stance and a one-leg stand (unsupported leg in the saggital plane) performed with the eyes closed, and a Stork Stand (unsupported leg in the frontal plane) with both eyes open and closed. In each position postural deviations were tallied for each individual while muscle recruitment was determined using root mean squared (RMS) EMG activity for the soleus, biceps femoris, erector spinae, rectus abdominis and internal oblique muscles of the dominant foot side. Balance scores were significantly improved post training in both the Balance Error Score System (p < 0.05) and stork stand positions (p < 0.01). Muscle activity was reduced post-training in all muscles in each condition except the soleus in the tandem position, although not all significantly. Reduced biceps femoris activity suggest that improved core stability allowed participants to move from a hip to an ankle postural control strategy through improved coordination of muscles involved in balance and reduced body sway. The core muscles were able to control body position with less activity post training suggesting improved muscle coordination and efficiency. These results suggest that short term progressive floor to BOSUTM balance training can improve standing balance in middle aged women. PMID- 26891634 TI - Differential activation of scapular muscles, during arm elevation, with and without trigger points. AB - BACKGROUND: Latent Myofascial Trigger Points (LMTrPs) are defined as certain pain free hyperirritable spots in a muscle taut band which lead to muscle activation pattern alternation in both loaded and unloaded conditions during scaption. The current study aimed to investigate the onset of upward scapular rotator muscle activations during rapid arm elevation in three planes of movement in patients with upper trapezius LMTrPs compared to healthy control participants. METHOD: Three planes of scapular movement were evaluated. The onset of Deltoid (DEL) was considered as the starting point in marking the onset of Upper Trapezius (UT) and Serratus Anterior (SA) muscle activations. RESULTS: There were significant differences in the relative muscle latencies between the LMTrPs and the control group. Those with LMTrPs showed a delayed and inconsistent activity of UT during all three planes of elevation (p < 0.05) and the same pattern happened for SA during flexion (p < 0.05). CONCLUSIONS: Both hosted and synergistic muscles experience delay in muscle activation and alterations in their recruitment pattern during rapid arm elevation in all planes of movement. These changes may serve as adaptive motor control strategies due to the presence of LMTrPs in UT muscles. PMID- 26891635 TI - Equilibrium in women with osteoporosis submitted to balance training with and without an oscillating vibratory pole. AB - OBJECTIVES: An eight-week balance training program, with and without oscillation of vibratory pole, was shown to have a medium-term persistence effect on the performance of elderly physically-active women with osteoporosis. METHODS: The 29 women who completed the study were randomly separated into two groups: an Oscillating Pole Group (OPG; 69.6 +/- 5.8 years; n = 14) and a Non-Oscillating Pole Group (NPG; 70.9 +/- 7.4 years; n = 15). The improvement in equilibrium was evaluated using the Berg Balance Scale before training, after training and in the Follow-Up (eight-weeks after the conclusion of the training). RESULTS AND DISCUSSION: The NPG presented both Post-Training (p = .018 relative to pre training) and Follow-Up (p = .007) improvements in equilibrium. The improvement for OPG was near significant (p = .051 relative to pre-training) in Post-Training and significant (p = .038) in the Follow-Up. There were no significant differences between Post-Training and Post-Follow-Up (p = .999) for either group or in the intergroup comparisons (no statistically-significant effect of oscillation of the pole). PMID- 26891636 TI - Pilot study of the effects of mixed light touch manual therapies on active duty soldiers with chronic post-traumatic stress disorder and injury to the head. AB - This pilot study was designed to examine the effects of mixed Light Touch Manual Therapies (LTMT) on headache, anxiety and other symptoms suffered by active duty United States service members experiencing chronic Post-Traumatic Stress Disorder (PTSD). Ten service members diagnosed with PTSD and having a self-reported injury to the head acquired at least two years prior, were provided with two hour-long sessions of mixed LTMT given a week apart. Data to assess the immediate and durable effects were gathered before and after the LTMT sessions. Results indicate that headache, anxiety, and pain interference were significantly reduced during the course of the pilot study. This suggests that mixed LTMT may be helpful in reducing some of the symptoms of PTSD and injury to the head. Further studies will be needed to determine if LTMT is an effective non-pharmacological treatment for headache, anxiety or other problems associated with PTSD or injury to the head. PMID- 26891637 TI - Range of motion and cervical myofascial pain. AB - Several studies investigating myofascial pain syndrome include assessments of range of motion (ROM) as a diagnostic criterion. However, the value of ROM in this context has not yet been evaluated in controlled clinical studies. We aimed to examine whether patients with myofascial pain syndrome display alterations of ROM when compared to healthy subjects. Twenty-two individuals (13 females, 9 males; aged 33.4 +/- 13.9 yrs) afflicted with active myofascial trigger points in the upper trapezius muscle as well as 22 age and sex matched healthy controls were included. All subjects underwent an examination of maximal active cervical ROM in flexion/extension assessed by means of a 3D ultrasonic movement analysis system (30 Hz; Zebris CMS 70). In the patients group, pressure pain threshold (PPT) of the trigger points was determined using a pressure algometer. Maximum range of motion in the sagittal plane did not differ between individuals with MTrP (125.9 +/- 23.2 degrees , 95% CI: 116.2-135.6 degrees ) and asymptomatic subjects (128.2 +/- 20.4 degrees , 95% CI: 119.7-136.7 degrees ; p > .05). In patients, PPT (1.7 +/- .6, 95% CI: 1.5-1.9) was not correlated with cervical mobility (r = -.13; p > .05). Based on these pilot data, range of motion in flexion/extension is not a valid criterion for the detection of myofascial trigger points. Additional research incorporating movement amplitudes in other anatomical planes and additional afflicted muscles should be conducted in order to further delineate the relative impact of MTrP on range of motion. PMID- 26891639 TI - Walking with a four wheeled walker (rollator) significantly reduces EMG lower limb muscle activity in healthy subjects. AB - OBJECTIVE: To investigate the immediate effect of four-wheeled- walker(rollator)walking on lower-limb muscle activity and trunk-sway in healthy subjects. METHODS: In this cross-sectional design electromyographic (EMG) data was collected in six lower-limb muscle groups and trunk-sway was measured as peak to-peak angular displacement of the centre-of-mass (level L2/3) in the sagittal and frontal-planes using the SwayStar balance system. 19 subjects walked at self selected speed firstly without a rollator then in randomised order 1. with rollator 2. with rollator with increased weight-bearing. RESULTS: Rollator walking caused statistically significant reductions in EMG activity in lower-limb muscle groups and effect-sizes were medium to large. Increased weight-bearing increased the effect. Trunk-sway in the sagittal and frontal-planes showed no statistically significant difference between conditions. CONCLUSION: Rollator walking reduces lower-limb muscle activity but trunk-sway remains unchanged as stability is likely gained through forces generated by the upper-limbs. Short term stability is gained but the long-term effect is unclear and requires investigation. PMID- 26891638 TI - Bracing and exercise-based treatment for idiopathic scoliosis. AB - BACKGROUND: Various conservative therapies are available for treating adolescent idiopathic scoliosis (AIS), however, the disparities between them and the evidence of their efficacy and effectiveness is still unclear. OBJECTIVES: To evaluate the effectiveness of different conservative treatments on AIS. METHODS: A literature-based narrative review of the English language medical literature. RESULTS AND CONCLUSIONS: The most appropriate treatment for each patient should be chosen individually and based on various parameters. Bracing has been found to be a most effective conservative treatment for AIS. There is limited evidence that specific physical exercises also an effective intervention for AIS. Exercise based physical therapy, if correctly administered, can prevent a worsening of the curve and may decrease need for bracing. In addition, physical exercises were found to be the only treatment improving respiratory function. Combining bracing with exercise increases treatment efficacy compared with a single treatment. Additional, well-designed and good quality studies are required to assess the effectiveness of different conservative methods in treating AIS. PMID- 26891640 TI - Equipment-based Pilates reduces work-related chronic low back pain and disability: A pilot study. AB - OBJECTIVE: This study investigated effectiveness of an equipment-based Pilates protocol for reducing pain and disability in individuals with work-related chronic low back pain (CLBP). METHODS: Twelve workers with non-specific CLBP participated in a quasi-experimental, one-group, pretest-posttest pilot study of supervised 6-week equipment-based Pilates exercise. Pain severity was assessed using a 100-mm visual analog scale (VAS). Physical function was assessed using the Oswestry disability index (ODI). RESULTS: The Pilates intervention significantly reduced pain (mean decrease in VAS 30.75 +/- 20.27, p < 0.0001) and disability (mean decrease in ODI 11.25 +/- 13.20, p < 0.02) with large and borderline large effect sizes, respectively. CONCLUSIONS: Rehabilitative Pilates exercise reduced pain and disability in workers with CLBP. Further research is needed to investigate Pilates exercise for rehabilitation of work-related injuries in large populations. PMID- 26891641 TI - Basic Body Awareness Therapy for patients with stroke: Experiences among participating patients and physiotherapists. AB - BACKGROUND: After a stroke many patients have muscle weakness, spasticity and compromised sensation leading to decreased postural stability. Basic Body Awareness Therapy includes slow movements that challenge postural control. AIM: The aim was to describe experiences of 8 weeks of Basic Body Awareness Therapy from the perspective of both patients with stroke and physiotherapists. METHOD: This study had a qualitative design. Twenty-one patients and four physiotherapists were interviewed. The interviews were analysed using manifest and latent content analysis. RESULTS: One overall theme emerged "Simple yet challenging" which was based on six categories: "Facing one's limitations", "Individualized movements", "A feeling of harmony", "Improved balance", "Integrated knowledge" and "Frustration and doubt". The patients described improvement in balance and stability, as well as increased wellbeing. CONCLUSION: The patients and physiotherapists related that Basic Body Awareness Therapy challenges balance but also provides an opportunity to reflect on the body. PMID- 26891642 TI - Both anticipatory and compensatory postural adjustments are adapted while catching a ball in unstable standing posture. AB - The main objective of this study was to analyze the role of balance exercises on anticipatory (APA) and compensatory (CPA) postural adjustments in different conditions of postural stability. Sixteen subjects were required to catch a ball while standing on rigid floor, trampoline and foam cushion surfaces. Electromyographic activities (EMG) of postural muscles were analyzed during time windows typical for APAs and CPAs. Overall there were a reciprocal activation of the muscles around the ankle and co-activations between ventral and dorsal muscles of the thigh and trunk during the catching a ball task. Compared to the rigid floor, the tibialis anterior activation was greater during the trampoline condition (CPA: p = 0.006) and the soleus muscle inhibition was higher during foam cushion condition (APA: p = 0.001; CPA: p = 0.007). Thigh and trunk muscle activities were similar across the conditions. These results advance the knowledge in postural control during body perturbations standing on unstable surfaces. PMID- 26891643 TI - A pilot study of balance performance benefit of myofascial release, with a tennis ball, in chronic stroke patients. AB - BACKGROUND: We hypothesised that the balance of spastic chronic stroke patients is related to myofascial problems. We performed myofascial release (MFR) with a tennis ball on the affected limb, as suggested by Myers. PURPOSE: This study investigated the benefits of 8 weeks of MFR using a tennis ball on the balance of spastic patients. METHODS: Eight stroke patients were enrolled voluntarily after providing informed consent. All subjects received 8-week interventions with MFR using a tennis ball three times per week. The patients were evaluated using the Berg Balance Scale (BBS) and Timed 'Up & Go' (TUG) test before and after 4 and 8 weeks of the intervention. RESULTS: There were significant differences in the BBS scores (p = 0.001). The TUG time decreased significantly at 4 and 8 weeks (p = 0.034). CONCLUSION: Myofascial release appears to improve the balance of spastic chronic stroke patients; however, further studies should evaluate the effective of MFR on walking in stroke patients and determine the mechanism of the effect of MFR. PMID- 26891644 TI - Multifactoral measures of fall risk in the visually impaired population: A pilot study. AB - OBJECTIVE: To determine the feasibility of taking multiple measures of visual and physical function in adults with visual impairment. A second objective was to obtain preliminary data on risk for falls in this population. DESIGN: Cohort feasibility study. SETTING: University ambulatory patient care center and research center. PARTICIPANTS: Convenience sample of community-dwelling men and women over age 18 with visual impairment (n = 12). Thirteen subjects were enrolled in the study; one was subsequently excluded due to self-reported cognitive decline at time of testing. Subjects were grouped by prospective fall incidence. INTERVENTIONS: Verbal education. MAIN OUTCOME MEASURES: Subjective measures of function; objective measures of visual and physical function. RESULTS: Visually impaired adults can safely complete a battery of physical functions to predict fall risk. Recent onset of visual impairment was correlated with higher fall risk [-0.53 +/- 0.22, p = 0.04]. CONCLUSIONS: It is feasible for an interdisciplinary team to measure risk for falls in adults with a visual impairment. Further investigation is needed to identify predictors of falls in adults of all ages with visual impairment. PMID- 26891645 TI - Effect of the Pilates method on women with temporomandibular disorders: A study protocol for a randomized controlled trial. AB - BACKGROUND: There is no consensus regarding the influence of temporomandibular disorders (TMD) on postural changes, but it is believed that an imbalance in one may influence the other. The aim of this study is to evaluate changes in the level of pain, the severity of TMD, the EMG activity of masticatory muscles and posture of young women undergoing training in Pilates, as well as correlating postural changes, pain level, severity of TMD and EMG activity of masticatory muscles. METHODS/DESIGN: A randomized clinical trial with blinded assessors will be held. 40 patients divided randomly into two groups will be assessed. The control group will receive conventional treatment with occlusal splint while the intervention group, in addition to conventional treatment will participate in Pilates sessions. Both groups will consist of women aged 18-35 years with TMD and pain. The research follow-up period will be 15 weeks. PMID- 26891646 TI - Effects of scapular stabilization exercise on pain related parameters in patients with scapulocostal syndrome: A randomized controlled trial. AB - The aim of this study was to evaluate the effects of scapular stabilization exercise (SSE) on pain intensity, pressure pain threshold (PPT), muscle tension and anxiety in patients with scapulocostal syndrome (SCS). Thirty-six patients were randomly assigned to receive a 30-minute session of either SSE or control (relaxed by lying supine quietly) for 12 sessions over a period of 4 weeks. Pain intensity, PPT, muscle tension and anxiety were assessed before and after a 4 week intervention period and 2 weeks after the intervention period. The adverse effects were evaluated after completion of the intervention period. Results indicated that the SSE group showed a significant improvement in all parameters after the intervention period and at 2 weeks after the intervention period (p < 0.05). For all outcomes, similar changes were not found in the control group. The adjusted post-test mean values of each assessment time point for pain intensity, muscle tension and anxiety were significantly lower in the SSE group than those of the control group (p < 0.05). Moreover, the values for PPT were significantly higher in the SSE group (p > 0.05). There were no reports of adverse effects in either group. We therefore conclude that SSE can improve pain related parameters and could be an effective intervention for SCS. PMID- 26891647 TI - Effects of the Pilates method on variables related to functionality of a patient with traumatic spondylolisthesis at L4-L5: A case study. AB - INTRODUCTION: Traumatic spondylolisthesis at L4-L5 is a rare complication in the spine, which impairs variables related to the functionality of the person affected. OBJECTIVE: To verify the effects of the Pilates method on strength and muscular resistance, flexibility, postural balance and level of pain in a patient with traumatic spondylolisthesis at L4-L5. METHODS: The following evaluations were performed pre and post-intervention: resistance of the flexor and extensor muscles of the trunk; isokinetic peak torque of the extensor and flexor muscles of the knee; hip and torso flexibility; static postural balance; and the visual analog scale of pain. The treatment consisted of three weekly sessions of Pilates, performed over 12 weeks. RESULTS: There was improvement in all the tests, except for one variable related to postural balance. CONCLUSIONS: The Pilates method was effective for improving muscle resistance and strength, flexibility, postural balance and pain, in a patient with traumatic spondylolisthesis at L4-L5. PMID- 26891650 TI - Fascial nomenclature. PMID- 26891649 TI - A fascia and the fascial system. PMID- 26891648 TI - Kinesiology taping does not change fibularis longus latency time and postural sway. AB - BACKGROUND: Kinesiology tape seems to improve muscle force, although little is known regarding its effect on latency time and postural sway. OBJECTIVES: To examine the effects of kinesiology taping on fibularis longus latency time and postural sway in healthy subjects. METHODS: Thirty participants were equally randomized into three groups, two experimental groups receiving kinesiology tape (EG1, from origin to insertion; EG2, from insertion to origin) and a control group. Before and 20-min after the intervention, postural sway was assessed on a force platform and fibularis longus latency time was recorded with surface electromyography during a sudden inversion perturbation. RESULTS: At baseline, no differences were found between groups regarding age, anthropometrics variables, postural sway and fibularis longus latency time. In both experimental groups, the application of tape did not change postural sway and fibularis longus latency time (EG1: 93.7 +/- 15.0 to 89.9 +/- 15.6 ms; EG2, 81.24 +/- 14.21 to 81.57 +/- 16.64, p < 0.05). Also, no changes were observed in the control group. CONCLUSION: Kinesiology tape seems not to enhance fibularis longus reaction time and postural sway in young healthy subjects. PMID- 26891651 TI - A critical overview of the current myofascial pain literature - January 2016. AB - Reflecting on the past year, the number of publications on myofascial pain continues to increase in a steady rate. The current review includes 30 basic and clinical studies, case reports, reviews, and reports from fifteen different countries about trigger points (TrP), myofascial pain (MP), dry needling (DN) and other related interventions. We are pleased that during 2015 this article made the top 15 of most downloaded articles as many as three times! In general, the quality of published papers is improving as well. Nevertheless, several papers included in this overview, mention the application of "ischemic compression", which is a questionable concept in the context of TrP inactivation. As we have outlined previously, in the current thinking about myofascial pain, TrPs feature significant hypoxia and a lowered pH (Ballyns et al., 2011; Shah and Gilliams, 2008), and attempts to induce more ischemia would be counterproductive. Already in 1999, Simons, Travell and Simons changed the terminology from ischemic compression to TrP compression (Simons et al., 1999) and we recommend that contemporary researchers and clinicians adopt the new terminology and stop using the term "ischemic compression." PMID- 26891652 TI - Prevalence and characteristics of women who consult with osteopathic practitioners during pregnancy; a report from the Australian Longitudinal Study on Women's Health (ALSWH). AB - BACKGROUND/AIM: The use of complementary medicine (CM) is common during pregnancy with visits to osteopathic practitioners growing in recent years. This study was conducted to investigate the prevalence and characteristics of women who consult osteopathic practitioners during pregnancy. METHOD: The study sample was obtained via the Australian Longitudinal Study on Women's Health (ALSWH). The women answered questions about consultations with osteopathic practitioners, pregnancy related health concerns and attitudes to CM use. RESULTS: A total response rate of 79.2% (1835) was obtained. Of these, 104 women (6.1%) consulted with an osteopath during pregnancy for a pregnancy-related health condition. Women were more likely to consult an osteopath if they suffered from back pain, sadness, weight management issues, or had a history of retained placenta. CONCLUSION: Women are visiting osteopaths for help with common pregnancy health complaints, highlighting the need for research to evaluate the safety, clinical and cost effectiveness of osteopathy in pregnancy. PMID- 26891653 TI - New is the well-forgotten old: The use of dry cupping in musculoskeletal medicine. AB - Cupping is an ancient technique used in treating pain and various disorders. Different techniques have been developed over time, however, applying a cup to create suction over a painful area, is common to all. Dry or fire cupping, used on the intact skin, leaves bluish circular hematomas. Recently, interest in cupping has re-emerged and subsequently, several studies have begun to investigate the mechanisms of cupping therapy. Mechanically, cupping increases blood circulation, whereas physiologically it activates the immune system and stimulates the mechanosensitive fibers, thus leading to a reduction in pain. There is initial scientific evidence that dry cupping is able to reduce musculoskeletal pain. Since cupping is an inexpensive, noninvasive and low-risk (if performed by a trained practitioner) therapeutic modality, we believe that it should be included in the arsenal of musculoskeletal medicine. It is essential to perform additional studies clarifying the biological mechanism and clinical effects of cupping. PMID- 26891654 TI - Dynamic tape. Is it all about controlling load? PMID- 26891655 TI - A tailored exercise program versus general exercise for a subgroup of patients with low back pain and movement control impairment: Short-term results of a randomised controlled trial. AB - BACKGROUND: Exercise is an effective treatment for patients with sub-acute and chronic low back pain (LBP). Patients with a movement control impairment (MCI) can be diagnosed as a subgroup of patients with LBP. Unknown is which exercise intervention is most beneficial for this subgroup. This study assessed the short term effect of a specific exercise program targeting movement control impairment versus general exercise treatment on disability in patients with LBP and MCI. METHODS: In a multicentre parallel group randomised controlled pragmatic trial, patients with sub-acute and chronic LBP were included. Further inclusion criteria were disability of >=5 points on the Roland-Morris Disability Questionnaire and >=2 positive tests out of a set of 6 movement control impairment tests. A total of 106 patients were randomly assigned to either tailored movement control exercise intervention (MC, n = 52) or a general exercise intervention (GE, n = 54); both 9-18 individual treatment sessions, over a maximum of 12 weeks. The primary outcome was disability measured with the Patient Specific Functional scale (PSFS). Secondary outcome was the Roland-Morris disability scale (RMDQ). Measurements were taken pre- and posttreatment. RESULTS: No significant difference was found following the treatment period. Baseline-adjusted between group mean difference for the PSFS was 0.5 (SD = 0.5; p = 0.32) in favour of MC exercises. The Roland-Morris Disability Questionnaire revealed a significant, but not clinically relevant, between-group difference of 2.0 points (SD = 0.8; p = 0.01). CONCLUSION: Disability in LBP patients was reduced considerably by both interventions. However, the limited contrast between the two exercise programs may have influenced outcomes. PMID- 26891658 TI - The Windowpane Squat. PMID- 26891656 TI - Influence of kinesio tape application direction on peak force of biceps brachii muscle: A repeated measurement study. AB - BACKGROUND: According to the kinesio tape (KT) method, proximal-to-distal (P-to D) application of KT should facilitate muscle activity (increase strength), distal-to- proximal (D-to-P) should decrease muscle activity (decrease strength) and applications in other directions should not influence muscle strength. OBJECTIVE: To evaluate the influence of KT application direction on peak force of biceps brachii in healthy subjects. METHODS: 16 students participated in a single group repeated measurements study. KT was applied randomly on both anterior arms as follows: no KT; P-to-D; D-to-P; or two horizontal stripes. Peak force of biceps was measured after each application by a blinded investigator. RESULTS: No difference in biceps peak force was found after evaluating no KT, P-to-D and D-to P. After the horizontal application, peak force was found statistically significantly higher than in the other conditions. CONCLUSIONS: Traditional assumptions of the KT method, suggesting that P-to-D application stimulates muscle and D-to-P relaxes the muscle, seem to be false. However, we do confirm that applying KT in various directions differently effects muscle strength. PMID- 26891657 TI - Correlation between deep cervical flexor muscle thickness at rest and sternocleidomastoid activity during the craniocervical flexion test. AB - The purpose of this study was to clarify the relationship between the thickness of the deep cervical flexor muscles (longus capitis and longus colli) at rest and sternocleidomastoid activity during the craniocervical flexion test (CCFT). Thirteen healthy males participated in this study. The thickness of the deep cervical flexor muscles was measured by ultrasound imaging in a relaxed supine position. Activity of the sternocleidomastoid was measured by electromyography during the CCFT at five incremental levels (22, 24, 26, 28, and 30 mm Hg). Correlations between normalized muscle thickness relative to body mass index and sternocleidomastoid activity were determined. Significant negative correlations were observed between normalized muscle thickness and activity of the sternocleidomastoid at 26 (r = -0.622, P = 0.023) and 28 mmHg (r = -0.653, P = 0.015). Individuals with smaller deep cervical flexor muscles exhibited increased activity in the sternocleidomastoid during the CCFT. PMID- 26891659 TI - Radiologic Percutaneous Gastrostomy in Nondistended Stomach: A Modified Approach. AB - INTRODUCTION: Gastrostomy tube placement for patients requiring long-term nutritional support may be performed using different techniques including endoscopic, surgical, and percutaneous radiologically guided methods. Radiologically inserted gastrostomy (RIG), typically performed when percutaneous endoscopic gastrostomy is not possible, requires proper gastric distension that is achieved by insufflating air through a nasogastric tube. We describe a simple technique to prevent air escape from the stomach during gastrostomy tube placement. To the best of our knowledge, this technique has not yet been described in the literature. MATERIALS AND METHODS: Four patients with unsuccessful percutaneous endoscopic gastrostomy were referred for fluoroscopic guided gastrostomy. One patient had a pyriform sinus tumor and three had an ischemic stroke causing dysphagia. Gastric distention was not achieved in the patients due to air escaping into the bowel during the standard RIG procedure. A modified approach using a balloon catheter inflated in the pylorus to avoid air passing into the duodenum permitted successful RIG. RESULTS: The modified RIG procedure was successfully carried out in all cases without complications. DISCUSSION: Inadequate air distension of the stomach is an unusual event that causes a failure of gastrostomy tube placement and an increased risk of both major and minor complications. The use of a balloon catheter inflated in the first part of the duodenum prevents the air passage into the bowel allowing the correct positioning of the gastrostomy. PMID- 26891660 TI - Platelet-derived Growth Factor Receptor-beta is Differentially Regulated in Primary Mouse Pericytes and Brain Slices. AB - Pericytes are perivascular cells and have heterogenous roles in the brain, such as controlling blood flow and entry of immune cells or regulating the blood-brain barrier. Platelet-derived growth factor (PDGF) receptor-beta (PDGFRbeta) is highly expressed in pericytes, representing the most selective biomarker. The aim of the present study was to culture primary mouse pericytes and to determine the expression pattern by Western Blot as well as immunostainings. We will study the effects of different exogenous stimuli (such as transforming growth factor-beta (TGFbeta1), PDGF-BB, oxygendeprivation, beta-amyloid or serumfree conditions) on the different pericyte markers. Using Western Blot analyses, we show that PDGFRbeta is selectively expressed in pericytes as a 160 kDa protein. Nestin, although not exclusively specific, is also expressed by pericytes, but markedly downregulated under serum-free conditions. PDGF-BB and oxygen-deprivation dramatically reduced PDGFRbeta expression, while TGFbeta1 increased its expression. The expression of PDGFRbeta was intracellular as shown by confocal microscopy. Using Western Blot analyses, we demonstrate that pericytes also contain a 100 kDa PDGFRbeta protein. However, in contrast to cortex brain slices, pericytes do not express a phosphorylated (Y740) isoform. Interestingly, PDGF-BB markedly reduced the 160 kDa isoform of PDGFRbeta. In conclusion, our data show a detailed expression of different forms of PDGFRbeta in primary pericytes, which is different to brain slices. However, we suggest that PDGFRbeta is a highly selective marker for pericytes. PMID- 26891661 TI - Biomarkers in Post-stroke Depression. AB - Depression is the most frequent neuropsychiatric complication after a stroke. Post-stroke depression has a significant impact on the outcome and prognosis of affected patients. Its diagnosis is complex and currently based only on clinical parameters. In recent years, efforts have been made to find biomarkers related to post-stroke outcomes, including complications such as depression. We carried out a systematic review of the literature looking for studies that investigated biomarkers associated with post-stroke depression (PSD) in Medline, Lilacs and PsycInfo databases. The results of 37 studies are discussed, describing the evidence for each evaluated biomarker. In conclusion, no evidence was found supporting the use of a particular biomarker for PSD. However, several changes were observed in inflammatory balance, oxidative stress, glutamatergic neurotransmission, production of neurotrophic factors, and genetic susceptibility that can be related to PSD. Research in the area of post-stroke biomarkers has the potential to provide personalized approach of stroke patients, also aiding in the diagnosis and understanding of the pathophysiology of this common neuropsychiatric complication. PMID- 26891662 TI - Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitus. AB - This study was designed to investigate the effects of treatment with the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX) in intracellular pathways in the brain of diabetic rats. To conduct this study we induced diabetes in Wistar rats with a single injection of alloxan, and afterwards rats were treated with NAC or DFX for 14 days. Following treatment completion, the immunocontent of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase 38 (MAPK38), brain-derived neurotrophic factor (BDNF), and protein kinases A and C (PKA and PKC) were determined in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). DFX treatment increased JNK content in the PFC and NAc of diabetic rats. In the amygdala, JNK was increased in diabetics treated with saline or NAC. MAPK38 was decreased in the PFC of control and in diabetic rats treated with NAC or DFX; and in the NAc in all groups. PKA was decreased in the PFC with DFX treatment. In the amygdala, PKA content was increased in diabetic rats treated with either saline or NAC, compared to controls; and it was decreased in either NAC or DFX-treated groups, compared to saline-treated diabetic animals. In the NAc, PKA was increased in NAC-treated diabetic rats. PKC was increased in the amygdala of NAC-treated diabetic rats. In the PFC, the BDNF levels were decreased following treatment with DFX in diabetic rats. In the hippocampus of diabetic rats the BDNF levels were decreased. However, treatment with DFX reversed this effect. In the amygdala the BDNF increased with DFX in non-diabetic rats. In the NAc DFX treatment increased the BDNF levels in diabetic rats. In conclusion, both diabetes and treatment with antioxidants were able to alter intracellular pathways involved in the regulation of cell survival in a brain area and treatment-dependent fashion. PMID- 26891663 TI - Knockdown of B7-H6 inhibits tumor progression and enhances chemosensitivity in B cell non-Hodgkin lymphoma. AB - B7 homologue 6 (B7-H6) is a new member of the B7 family molecules and is selectively expressed on tumor cells, especially in hematologic malignancies. However, the role of B7-H6 in lymphoma progression and chemosensitivity remains unclear. We determined the effects of downregulating B7-H6 expression on tumorigenesis and chemosensitivity in B-cell lymphoma. Stable B7-H6 knockdown in CA46 cells was established with a lentiviral system. The expression of mRNA was measured by PCR while protein expression was detected by western blotting and flow cytometry. Cell viability, apoptosis and cell cycle distribution were analyzed using CCK-8, colony formation and flow cytometry assays, respectively. Cell migration and invasion were determined using the Transwell chamber assay. B7 H6 was widely expressed in B-cell lymphomas. Knockdown of B7-H6 inhibited cell proliferation, colony formation and migration and invasion of lymphoma cells. After B7-H6 silencing, CA46 cells were arrested in G0/G1 phase. Moreover, the silencing of B7-H6 increased cell apoptosis and sensitivity to vincristine and dexamethasone. Investigation of expression of downstream targets of STAT3 supported a theory in which B7-H6 knockdown may confer an antitumor effect via abrogation of the STAT3 pathway. This study demonstrates that B7-H6 plays an important role in the pathogenesis and chemosensitivity of lymphoma. B7-H6 is therefore a potential clinical biomarker and therapeutic target in B-cell lymphomas. PMID- 26891664 TI - Drug-induced hypersensitivity syndrome by ethambutol: A case report. PMID- 26891665 TI - Erratum to: Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer. PMID- 26891666 TI - Regulation of proliferation, angiogenesis and apoptosis in hepatocellular carcinoma by miR-26b-5p. AB - MicroRNAs (miRNAs) play vital roles in cell proliferation, differentiation and apoptosis in hepatocellular carcinoma (HCC). miR-26b has been confirmed as an important regulator in carcinogenesis and other pathological processes. miR-26b 5p is one member of the mature miR-26 family, and its functional role in proliferation, angiogenesis and apoptosis in HCC remains unknown. Here, we demonstrate that miR-26b-5p expression was significantly decreased in HCC tissues and HCC cell lines compared with normal liver tissues and liver cells by quantitative real-time polymerase chain reaction (qRT-PCR). The relationships between miR-26b-5p and the clinical characteristics of HCC patients were further analysed, and miR-26b-5p was positively correlated with the differentiation of HCC cells. Computational searches were further used to identify the downstream targets and signalling pathways of miR-26b-5p in HCC cells. Cell viability, proliferation and tube formation abilities were assessed by scrape, 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and three-dimensional culture assays to confirm that miR-26b-5p inhibited HCC cell growth and impaired the tube formation ability of the HCC cells. Both in vitro and in vivo studies showed that miR-26b-5p could suppress vascular mimicry (VM) and angiogenesis by down-regulating the expression of VE-cadherin, Snail and MMP2 and could inhibit the apoptosis of HCC cells. Using mouse models, we revealed that tumours derived from miR-26b-5p-expressing HCC cells displayed a significant decrease in microvessel density compared with those derived from control cells. Therefore, our data provide further insight into the role of miR-26b-5p as a negative regulator of proliferation, angiogenesis, and apoptosis in HCC. PMID- 26891668 TI - Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line. AB - Leukemia is a hematological malignancy which is produced by uncontrolled proliferation of leukocyte precursors. Currently, alternative medicines, using herb extracts, have been developed for cancer treatment. In this study, the effect of diallyl disulfide (DADS) on the induction of apoptosis and autophagy was investigated in K562 and NB4 myeloid leukemia cells. Leukemia cells were treated with various concentrations of DADS for 24 and 48 h. The percentage of cell viability was measured using an MTT assay. The percentages of apoptosis and autophagy were analyzed by staining with annexin-FITC and anti-LC3 FITC conjugated antibodies, respectively. Then, the stained cells were detected by flow cytometry. In addition, PP242, a mammalian target rapamycin (mTOR) inhibitor, was used to study the involvement of the mTOR pathway in DADS-induced apoptosis and autophagy. mTOR mRNA expression was measured by real-time PCR. The results showed that DADS decreased cell viability and increased the percentage of cell apoptosis in a dose- and time-dependent manner. mTOR expression was significantly decreased in DADS- and mTOR inhibitor-treated cells. The highest percentages of apoptosis and autophagy were shown in cells treated with 100 MUg/ml DADS combined with 10 MUM of the mTOR inhibitor. According to our results, DADS could induce apoptosis and autophagy via the mTOR pathway in both K562 and NB4 myeloid leukemia cell lines. PMID- 26891667 TI - Platinum-zoledronate complex blocks gastric cancer cell proliferation by inducing cell cycle arrest and apoptosis. AB - A series of novel dinuclear platinum complexes based on the bisphosphonate ligands have been synthesized and characterized in our recent study. For the purpose of discovering the pharmacology and action mechanisms of this kind of compounds, the most potent compound [Pt(en)]2ZL was selected for systematic investigation. In the present study, the inhibition effect on the human gastric cancer cell lines SGC7901 and action mechanism of [Pt(en)]2ZL were investigated. The traditional 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and colony formation assay were carried out to study the effect of [Pt(en)]2ZL on the cell viability and proliferation capacity, respectively. The senescence-associated beta-galactosidase staining and immunofluorescence staining were also performed to assess the cell senescence and microtubule polymerization. Fluorescence staining and flow cytometry (FCM) were used to monitor the cell cycle distribution and apoptosis, and Western blot analysis was applied to examine the expression of several apoptosis-related proteins. The results demonstrated that [Pt(en)]2ZL exhibited remarkable cytotoxicity and anti proliferative effects on the SGC7901 cells in a dose- and time-dependent manner, and it also induced cell senescence and abnormal microtubule assembly. The cell apoptosis and cell cycle arrest induced by [Pt(en)]2ZL were also observed with the fluorescence staining and FCM. The expressions of cell cycle regulators (p53, p21, cyclin D1, cyclin E, and cyclin-dependent kinase (CDK)2) and apoptosis related proteins (Bcl-2, Bax, caspase-3, poly ADP ribose polymerase (PARP), and survivin) were regulated by the treatment of [Pt(en)]2ZL, resulting in the cell cycle arrest and apoptosis. Therefore, [Pt(en)]2ZL exerted anti-tumor effect on the gastric cancer via inducing cell cycle arrest at G1/S phase and apoptosis. PMID- 26891669 TI - A new evaluation of heat distribution on facial skin surface by infrared thermography. AB - OBJECTIVE: The aim of this study was to identify the facial areas defined by thermal gradient, in individuals compatible with the pattern of normality, and to quantify and describe them anatomically. METHODS: The sample consisted of 161 volunteers, of both genders, aged between 26 and 84 years (63 +/- 15 years). RESULTS: The results demonstrated that the thermal gradient areas suggested for the study were present in at least 95% of the thermograms evaluated and that there is significant difference in temperature between the genders, racial group and variables "odontalgia", "dental prothesis" and "history of migraine" (p < 0.05). Moreover, there was no statistically significant difference in the absolute temperatures between ages, and right and left sides of the face, in individuals compatible with the pattern of normality (DeltaT = 0.11 degrees C). CONCLUSIONS: The authors concluded that according to the suggested areas of thermal gradients, these were present in at least 95% of all the thermograms evaluated, and the areas of high intensity found in the face were medial palpebral commissure, labial commissure, temporal, supratrochlear and external acoustic meatus, whereas the points of low intensity were inferior labial, lateral palpebral commissure and nasolabial. PMID- 26891670 TI - Molecular aspects of monoamine oxidase B. AB - Monoamine oxidases (MAO) influence the monoamine levels in brain by virtue of their role in neurotransmitter breakdown. MAO B is the predominant form in glial cells and in platelets. MAO B structure, function and kinetics are described as a background for the effect of alterations in its activity on behavior. The need to inhibit MAO B to combat decreased brain amines continues to drive the search for new drugs. Reversible and irreversible inhibitors are now designed using data mining, computational screening, docking and molecular dynamics. Multi-target ligands designed to combat the elevated activity of MAO B in Alzheimer's and Parkinson's Diseases incorporate MAO inhibition (usually irreversible) as well as iron chelation, antioxidant or neuroprotective properties. The main focus of drug design is the catalytic activity of MAO, but the imidazoline I2 site in the entrance cavity of MAO B is also a pharmacological target. Endogenous regulation of MAO B expression is discussed briefly in light of new studies measuring mRNA, protein, or activity in healthy and degenerative samples, including the effect of DNA methylation on the expression. Overall, this review focuses on examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B. PMID- 26891671 TI - Clinics in diagnostic imaging (165). Oesophageal rupture secondary to malposition of an SB tube gastric balloon. AB - Oesophageal rupture is a life-threatening complication of balloon tamponade for bleeding oesophageal varices. We herein describe the clinical course and imaging findings in a 33-year-old Indian man who had a Sengstaken-Blakemore (SB) tube inserted for uncontrolled haematemesis, which was unfortunately complicated by malposition of the gastric balloon with resultant oesophageal rupture. The inflated SB tube gastric balloon was visualised within the right hemithorax on chest radiography after the SB tube insertion. Further evaluation of the thorax on computed tomography confirmed the diagnosis of oesophageal rupture associated with right-sided haemopneumothorax. It is crucial for both the referring clinician and reporting radiologist to recognise early the imaging features of an incorrectly positioned SB tube gastric balloon, so as to ensure prompt intervention and a reduction in patient morbidity and mortality. PMID- 26891672 TI - Evidence of a complex species controlling the setting reaction of glass ionomer cements. AB - OBJECTIVE: To elucidate the mechanism(s) responsible for the profound impact germanium has on the setting reaction of zinc silicate glass ionomer cements (GICs). METHODS: Five <45MUm glass powder compositions (0.48-xSiO2, xGeO2, 0.36 ZnO, 0.16 CaO; where x=0.12, 0.24, 0.36, 0.48mol. fraction) were synthesized. Glass degradation was assessed under simulated setting conditions using acetic acid from 0.5 to 60min, monitoring the concentrations of ions released using ICP OES. Subsequently, GICs were prepared by mixing fresh glass powders with polyacrylic acid (PAA, Mw=12,500g/mol, 50wt% aq. solution) at a 1:0.75 ratio. Cement structure and properties were evaluated using ATR-FTIR and rheology (for 60min), as well as 24h biaxial flexural strength. RESULTS: Reduced Si:Ge ratios yielded faster degrading glasses, yet contrary to expectation, the corresponding ATR-FTIR spectra indicated slower crosslinking within the GIC matrix. Rheology testing found the initial viscosity cement pastes reduced with decreased Si:Ge, and Ge containing cements all set significantly slower than the Si based GIC. Interestingly, biaxial flexural strength remained consistent regardless of setting behavior. SIGNIFICANCE: This counter-intuitive combination of behaviors is attributed to the presence of a chemical complex species specific to Ge containing glasses that delays, but does not hinder, the formation of the GIC matrix. These findings embody chemical complex species as a mechanism to decouple glass reactivity from cement setting rate, a mechanism with the potential to enhance the utility of GICs in both dental and orthopaedic applications. PMID- 26891673 TI - Pigment Degradation in Oil Paint Induced by Indoor Climate: Comparison of Visual and Computational Backscattered Electron Images. AB - For the first time the degradation of lead white pigment in mature oil paint has been used as an internal marker for the degree of saponification and hence chemical degradation of oil paint. Computational image analysis of the backscattered electron images quantified the degree of the intact lead white pigment versus the nonpigmented and lead-rich areas (degraded lead white) in the paint layers. This new methodology was applied to a series of paint samples taken from four painted wall hangings (dated 1778), which makes it possible to study the influence of indoor climate on chemical degradation of aged oil paintings. The visual interpretation and computational image analysis of the backscattered electron images revealed clear trends. The highest degree of lead white degradation in the room was found in samples from the north wall close to the windows, whereas degradation diminished further away from the window. Lead white from the south wall was less degraded, but showed a similar trend as in the paintings on the north wall. These results imply a strong relationship between chemical degradation of paint and location of the paint in the room. PMID- 26891674 TI - Is mechanical ventilation a cure for ARDS? PMID- 26891675 TI - Risk of oxalate nephropathy with the use of cyanide antidote hydroxocobalamin in critically ill burn patients. PMID- 26891676 TI - Sensitivity and specificity of Critical Care Pain Observation Tool used for intubated patients following open-heart surgery. PMID- 26891678 TI - Acquisition of dental skills in preclinical technique courses: influence of spatial and manual abilities. AB - Sixty years of research have not added up to a concordant evaluation of the influence of spatial and manual abilities on dental skill acquisition. We used Ackerman's theory of ability determinants of skill acquisition to explain the influence of spatial visualization and manual dexterity on the task performance of dental students in two consecutive preclinical technique courses. We measured spatial and manual abilities of applicants to Hamburg Dental School by means of a multiple choice test on Technical Aptitude and a wire-bending test, respectively. Preclinical dental technique tasks were categorized as consistent-simple and inconsistent-complex based on their contents. For analysis, we used robust regression to circumvent typical limitations in dental studies like small sample size and non-normal residual distributions. We found that manual, but not spatial ability exhibited a moderate influence on the performance in consistent-simple tasks during dental skill acquisition in preclinical dentistry. Both abilities revealed a moderate relation with the performance in inconsistent-complex tasks. These findings support the hypotheses which we had postulated on the basis of Ackerman's work. Therefore, spatial as well as manual ability are required for the acquisition of dental skills in preclinical technique courses. These results support the view that both abilities should be addressed in dental admission procedures in addition to cognitive measures. PMID- 26891680 TI - Pollution characterization of liquid waste of the factory complex Fertial (Arzew, Algeria). AB - The industrial development in Algeria has made a worrying situation for all socioeconomic stakeholders. Indeed, this economic growth is marked in recent years by the establishment of factories and industrial plants that discharge liquid waste in marine shorelines. These releases could destabilize the environmental balance in the coming years, hence the need to support the processing of all sources of pollution. Remediation of such discharges requires several steps of identifying the various pollutants to their treatments. Therefore, the authors conducted this first work of characterization of industrial effluents generated by the mineral fertilizer factory complex Fertial (Arzew), and discussed the pollution load generated by this type of industry. This monitoring would establish a tool for reflection and decision support developed by a management system capable of ensuring effective and sustainable management of effluents from industrial activities of Fertial. IMPLICATIONS: The authors conducted this first work of characterization of industrial effluents generated by the mineral fertilizer factory complex Fertial (Arzew), and discussed the pollution load generated by this type of industry. This monitoring would establish a tool for reflection and decision support developed by a management system capable of ensuring effective and sustainable management of effluents from industrial activities of Fertial. PMID- 26891677 TI - Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. AB - PURPOSE: In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock. METHODS: We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60 65 mmHg) versus a higher (75-80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups. RESULTS: A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95% CI 7-11). In the lower and higher MAP groups, we observed deviations on 12 versus 8% of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36%, p = 0.07) and hospital mortality (30 versus 33%, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60%, p = 0.03) but not in younger patients. CONCLUSIONS: This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy. PMID- 26891679 TI - The attributes of an effective teacher differ between the classroom and the clinical setting. AB - Most training programs use learners' subjective ratings of their teachers as the primary measure of teaching effectiveness. In a recent study we found that preclinical medical students' ratings of classroom teachers were associated with perceived charisma and physical attractiveness of the teacher, but not intellect. Here we explored whether the relationship between these variables and teaching effectiveness ratings holds in the clinical setting. We asked 27 Internal Medicine residents to rate teaching effectiveness of ten teachers with whom they had worked on a clinical rotation, in addition to rating each teacher's clinical skills, physical attractiveness, and charisma. We used linear regression to study the association between these explanatory variables and teaching effectiveness ratings. We found no association between rating of physical attractiveness and teaching effectiveness. Clinical skill and charisma were independently associated with rating of teaching effectiveness (regression coefficients [95 % confidence interval] 0.73 [0.60, 0.85], p < 0.001 and 0.12 [0.01, 0.23], p = 0.03, respectively). The variables associated with effectiveness of classroom and clinical teachers differ, suggesting context specificity in teaching effectiveness ratings. Context specificity may be explained by differences in the exposure that learners have to teachers in the classroom versus clinical setting so that raters in the clinical setting may base ratings upon observed behaviours rather than stereotype data. Alternatively, since subjective ratings of teaching effectiveness inevitably incorporate learners' context-specific needs, the attributes that make a teacher effective in one context may not meet the needs of learners in a different context. PMID- 26891681 TI - Greenhouse gas emissions from dairy open lot and manure stockpile in northern China: A case study. AB - The open lots and manure stockpiles of dairy farm are major sources of greenhouse gas (GHG) emissions in typical dairy cow housing and manure management system in China. GHG (CO(2), CH(4) and N(2)O) emissions from the ground level of brick paved open lots and uncovered manure stockpiles were estimated according to the field measurements of a typical dairy farm in Beijing by closed chambers in four consecutive seasons. Location variation and manure removal strategy impacts were assessed on GHG emissions from the open lots. Estimated CO(2), CH(4) and N(2)O emissions from the ground level of the open lots were 137.5+/-64.7 kg hd(-1) yr( 1), 0.45+/-0.21 kg hd(-1) yr(-1) and 0.13+/-0.08 kg hd(-1) yr(-1), respectively. There were remarkable location variations of GHG emissions from different zones (cubicle zone vs. aisle zone) of the open lot. However, the emissions from the whole open lot were less affected by the locations. After manure removal, lower CH(4) but higher N(2)O emitted from the open lot. Estimated CO(2), CH(4) and N(2)O emissions from stockpile with a stacking height of 55+/-12 cm were 858.9+/ 375.8 kg hd(-1) yr(-1), 8.5+/-5.4 kg hd(-1) yr(-1) and 2.3+/-1.1 kg hd(-1) yr( 1), respectively. In situ storage duration, which estimated by manure volatile solid contents (VS), would affect GHG emissions from stockpiles. Much higher N(2)O was emitted from stockpiles in summer due to longer manure storage. IMPLICATIONS: This study deals with greenhouse gas (GHG) emissions from open lots and stockpiles. It's an increasing area of concern in some livestock producing countries. The Intergovernmental Panel on Climate Change (IPCC) methodology is commonly used for estimation of national GHG emission inventories. There is a shortage of on-farm information to evaluate the accuracy of these equations and default emission factors. This work provides valuable information for improving accounting practices within China or for similar manure management practice in other countries. PMID- 26891682 TI - Weak localization effect in topological insulator micro flakes grown on insulating ferrimagnet BaFe12O19. AB - Many exotic physics anticipated in topological insulators require a gap to be opened for their topological surface states by breaking time reversal symmetry. The gap opening has been achieved by doping magnetic impurities, which however inevitably create extra carriers and disorder that undermine the electronic transport. In contrast, the proximity to a ferromagnetic/ferrimagnetic insulator may improve the device quality, thus promises a better way to open the gap while minimizing the side-effects. Here, we grow thin single-crystal Sb1.9Bi0.1Te3 micro flakes on insulating ferrimagnet BaFe12O19 by using the van der Waals epitaxy technique. The micro flakes show a negative magnetoresistance in weak perpendicular fields below 50 K, which can be quenched by increasing temperature. The signature implies the weak localization effect as its origin, which is absent in intrinsic topological insulators, unless a surface state gap is opened. The surface state gap is estimated to be 10 meV by using the theory of the gap induced weak localization effect. These results indicate that the magnetic proximity effect may open the gap for the topological surface attached to BaM insulating ferrimagnet. This heterostructure may pave the way for the realization of new physical effects as well as the potential applications of spintronics devices. PMID- 26891684 TI - Determination of a steroid profile in heel prick blood using LC-MS/MS. AB - BACKGROUND: The aim of this study was to improve the sensitivity of the congenital adrenal hyperplasia (CAH) neonatal screening by including second-tier steroid profiling on a DBS using LC-MS. RESULTS: We developed a method to measure the steroid profile in DBS and established gestational age-specific reference ranges of cortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, 17 hydroxyprogesterone, testosterone, Delta4-androstenedione, corticosterone and 11 deoxycorticosterone using 450 heel prick samples of neonates, participating in the Dutch Screening Program. Analyzing 92 cards with a positive CAH screening showed that only 21-deoxycortisol was 100% specific for diagnosed CAH patients. CONCLUSION: Steroid precursors can be measured in DBS and we suggest to implement the method as a second tier testing for CAH in The Netherlands. PMID- 26891683 TI - Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells. AB - Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a 'persister' state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit--and may even provide a latent reservoir of cells for--the emergence of heterogeneous drug-resistance mechanisms. PMID- 26891685 TI - Boldine suppresses dextran sulfate sodium-induced mouse experimental colitis: NF kappaB and IL-6/STAT3 as potential targets. AB - Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration, and upregulation of inflammatory mediators. Boldine is an alkaloid compound found in Boldo tree, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Hence, the effect of boldine for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced UC in BALB/c mice was studied. Administration of boldine to DSS-induced mice protects colon damage by reduced disease activity index, spleen weight, and increased colon length. Also administration of boldine showed a reduction in the activity of myeloperoxidase (MPO) and CD 68+ expression. Boldine reduced the colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis in vivo showed clear decrease in the production of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-6, IL-17, and signal transducer and activator of transcription-(p-STAT3)(Y705) with nuclear factor (p65-NF-kappaB) production being reduced significantly. Moreover, p65-NF-kappaB activation was reduced in mouse macrophage RAW 264.7 cells in vitro. The data demonstrated that boldine may be beneficial in colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of p65-NF-kappaB and STAT3 signaling pathways. (c) 2016 BioFactors, 42(3):247-258, 2016. PMID- 26891687 TI - Visa changes could lead to hundreds of doctors leaving the NHS, warns BMA. PMID- 26891686 TI - Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study. AB - BACKGROUND: Vertebral endplate (Modic) abnormalities are important structural lesions in the spine, but their association with body composition and fat distribution have not been examined. Moreover, no study has examined whether Modic change are related to other structural features of low back pain, such as reduced intervertebral disc height. METHODS: Seventy-two community-based individuals not selected for low back pain had lumbar vertebral Modic change and intervertebral disc height assessed from MRI. Dual energy x-ray absorptiometry measured body composition and fat distribution. RESULTS: The predominance of Modic change was type 2. Modic change was associated with an increased fat mass index (OR 1.20, 95 % CI 1.01 to 1.43), and tended to be associated with a reduced fat-free mass index (OR 0.62, 95 % CI 0.37 to 1.03, p = 0.07). While an increased percentage of gynoid fat was associated with a reduced risk (OR 0.62, 95 % CI 0.43 to 0.89), an increased percentage of android fat was associated with an increased risk of Modic change (OR 2.11, 95 % CI 1.18 to 3.76). Modic change was also associated with reduced intervertebral disc height at L2/3, L4/5 and L5/S1 (OR range 1.4 to 1.8; all p <= 0.03). CONCLUSION: Modic type 2 change is associated with reduced intervertebral disc height and an increased fat mass index. Whereas gynoid fat distribution protected against Modic type 2 change, an android pattern increased the risk of this lesion. Modic type 2 change, which histologically represent fat replacement, might have a metabolic component to its aetiology. PMID- 26891689 TI - Trapping the intruder - immune receptor domain fusions provide new molecular leads for improving disease resistance in plants. AB - A new study uses genomics to show that fusions of plant immune receptors and other protein domains occur in significant numbers. This finding will generate many new research hypotheses and provide new opportunities for breeding resistant plant varieties. PMID- 26891688 TI - CD200R1 agonist attenuates glial activation, inflammatory reactions, and hypersensitivity immediately after its intrathecal application in a rat neuropathic pain model. AB - BACKGROUND: Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases. METHODS: Immunofluorescence staining, western blot analysis, and RT-PCR were used to investigate the modulatory effects of CD200 fusion protein (CD200Fc) on activation of microglia and astrocytes as well as synthesis of pro- (TNF, IL 1beta, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in the L4-L5 spinal cord segments in relation to behavioral signs of neuropathic pain after unilateral sterile chronic constriction injury (sCCI) of the sciatic nerve. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were measured in hind paws 1 day before operation; 1, 3, and 7 days after sCCI operation; and then 5 and 24 h after intrathecal application of artificial cerebrospinal fluid or CD200Fc. RESULTS: Seven days from sCCI operation and 5 h from intrathecal application, CD200Fc reduced mechanical and thermal hypersensitivity when compared with control animals. Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels. Administration of CD200Fc also diminished elevation of CD200 and CD200R proteins as a concomitant reaction of the modulatory system to increased neuroinflammatory reactions after nerve injury. The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application. CONCLUSIONS: Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development. This may constitute a promising and novel therapeutic approach for the treatment of neuropathic pain. PMID- 26891690 TI - Do not let death do us part: 'find-me' signals in communication between dying cells and the phagocytes. AB - The turnover and clearance of cells is an essential process that is part of many physiological and pathological processes. Improper or deficient clearance of apoptotic cells can lead to excessive inflammation and autoimmune disease. The steps involved in cell clearance include: migration of the phagocyte toward the proximity of the dying cells, specific recognition and internalization of the dying cell, and degradation of the corpse. The ability of phagocytes to recognize and react to dying cells to perform efficient and immunologically silent engulfment has been well-characterized in vitro and in vivo. However, how apoptotic cells themselves initiate the corpse removal and also influence the cells within the neighboring environment during clearance was less understood. Recent exciting observations suggest that apoptotic cells can attract phagocytes through the regulated release of 'find-me' signals. More recent studies also suggest that these find-me signals can have additional roles outside of phagocyte attraction to help orchestrate engulfment. This review will discuss our current understanding of the different find-me signals released by apoptotic cells, how they may be relevant in vivo, and their additional roles in facilitating engulfment. PMID- 26891691 TI - Immunogenic versus tolerogenic phagocytosis during anticancer therapy: mechanisms and clinical translation. AB - Phagocytosis of dying cells is a major homeostatic process that represents the final stage of cell death in a tissue context. Under basal conditions, in a diseased tissue (such as cancer) or after treatment with cytotoxic therapies (such as anticancer therapies), phagocytosis has a major role in avoiding toxic accumulation of cellular corpses. Recognition and phagocytosis of dying cancer cells dictate the eventual immunological consequences (i.e., tolerogenic, inflammatory or immunogenic) depending on a series of factors, including the type of 'eat me' signals. Homeostatic clearance of dying cancer cells (i.e., tolerogenic phagocytosis) tends to facilitate pro-tumorigenic processes and actively suppress antitumour immunity. Conversely, cancer cells killed by immunogenic anticancer therapies may stimulate non-homeostatic clearance by antigen-presenting cells and drive cancer antigen-directed immunity. On the other hand, (a general) inflammatory clearance of dying cancer cells could have pro tumorigenic or antitumorigenic consequences depending on the context. Interestingly, the immunosuppressive consequences that accompany tolerogenic phagocytosis can be reversed through immune-checkpoint therapies. In the present review, we discuss the pivotal role of phagocytosis in regulating responses to anticancer therapy. We give particular attention to the role of phagocytosis following treatment with immunogenic or immune-checkpoint therapies, the clinical prognostic and predictive significance of phagocytic signals for cancer patients and the therapeutic strategies that can be employed for direct targeting of phagocytic determinants. PMID- 26891692 TI - Exposure of phosphatidylserine on the cell surface. AB - Phosphatidylserine (PtdSer) is a phospholipid that is abundant in eukaryotic plasma membranes. An ATP-dependent enzyme called flippase normally keeps PtdSer inside the cell, but PtdSer is exposed by the action of scramblase on the cell's surface in biological processes such as apoptosis and platelet activation. Once exposed to the cell surface, PtdSer acts as an 'eat me' signal on dead cells, and creates a scaffold for blood-clotting factors on activated platelets. The molecular identities of the flippase and scramblase that work at plasma membranes have long eluded researchers. Indeed, their identity as well as the mechanism of the PtdSer exposure to the cell surface has only recently been revealed. Here, we describe how PtdSer is exposed in apoptotic cells and in activated platelets, and discuss PtdSer exposure in other biological processes. PMID- 26891693 TI - NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. AB - Nod-like receptor, pyrin containing 3 (NLRP3) is characterized primarily as a canonical caspase-1 activating inflammasome in macrophages. NLRP3 is also expressed in the epithelium of the kidney and gut; however, its function remains largely undefined. Primary mouse tubular epithelial cells (TEC) lacking Nlrp3 displayed reduced apoptosis downstream of the tumor necrosis factor (TNF) receptor and CD95. TECs were identified as type II apoptotic cells that activated caspase-8, tBid and mitochondrial apoptosis via caspase-9, responses that were reduced in Nlrp3-/- cells. The activation of caspase-8 during extrinsic apoptosis induced by TNFalpha/cycloheximide (TNFalpha/CHX) was dependent on adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) and completely independent of caspase-1 or caspase-11. TECs and primary human proximal tubular epithelial cells (HPTC) did not activate a canonical inflammasome, caspase-1, or IL-1beta secretion in response to TNFalpha/CHX or NLRP3-dependent triggers, such as ATP or nigericin. In cell fractionation studies and by confocal microscopy, NLRP3 colocalized with ASC and caspase-8 in speck-like complexes at the mitochondria during apoptosis. The formation of NLRP3/ASC/caspase-8 specks in response to TNFalpha/CHX was downstream of TNFR signaling and dependent on potassium efflux. Epithelial ASC specks were present in enteroids undergoing apoptosis and in the injured tubules of wild-type but not Nlrp3-/- or ASC-/- mice following ureteric unilateral obstruction in vivo. These data show that NLRP3 and ASC form a conserved non-canonical platform for caspase-8 activation, independent of the inflammasome that regulates apoptosis within epithelial cells. PMID- 26891694 TI - Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease. AB - Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies. PMID- 26891696 TI - A longitudinal study of the durability of long-lasting insecticidal nets in Zambia. AB - BACKGROUND: A key goal of malaria control is to achieve universal access to, and use of, long-lasting insecticidal nets (LLINs) among people at risk for malaria. Quantifying the number of LLINs needed to achieve and maintain universal coverage requires knowing when nets need replacement. Longitudinal studies have observed physical deterioration in LLINs well before the assumed net lifespan of 3 years. The objective of this study was to describe attrition, physical integrity and insecticide persistence of LLINs over time to assist with better quantification of nets needing replacement. METHODS: 999 LLINs distributed in 2011 in two highly endemic provinces in Zambia were randomly selected, and were enrolled at 12 months old. LLINs were followed every 6 months up to 30 months of age. Holes were counted and measured (finger, fist, and head method) and a proportional hole index (pHI) was calculated. Households were surveyed about net care and repair and if applicable, reasons for attrition. Functional survival was defined as nets with a pHI <643 and present for follow-up. At 12 and 24 months of age, 74 LLINs were randomly selected for examination of insecticidal activity and content using bioassay and chemical analysis methods previously described by the World Health Organization (WHO). RESULTS: A total of 999 LLINs were enrolled; 505 deltamethrin treated polyester nets and 494 permethrin-treated polyethylene nets. With 74 used to examine insecticide activity, 925 were available for full follow-up. At 30 months, 325 (33 %) LLINs remained. Net attrition was primarily due to disposal (29 %). Presence of repairs and use over a reed mat were significantly associated with larger pHIs. By 30 months, only 56 % of remaining nets met criteria for functional survival. A shorter functional survival was associated with having been washed. At 24 months, nets had reduced insecticidal activity (57 % met WHO minimal criteria) and content (5 % met WHO target insecticide content). CONCLUSIONS: The median functional survival time for LLINs observed the study was 2.5-3 years and insecticide activity and content were markedly decreased by 2 years. A better measure of net survival incorporating insecticidal field effectiveness, net physical integrity, and attrition is needed. PMID- 26891697 TI - Evaluation of ceftriaxone utilization in medical and emergency wards of Tikur Anbessa specialized hospital: a prospective cross-sectional study. AB - BACKGROUND: Ceftriaxone is one of the most commonly used antibiotics due to its high antibacterial potency, wide spectrum of activity and low potential for toxicity. However, the global trend shows misuse of this drug. The aim of this study was to evaluate prospectively the appropriateness of ceftriaxone use in medical and emergency wards of Tikur Anbessa Specialized Hospital. METHODS: A prospective cross-sectional study was conducted by reviewing medication records of patients receiving ceftriaxone during hospitalization at Tikur Anbessa Specialized Hospital between February 1 and June 30, 2014. Drug use evaluation was conducted to determine whether ceftriaxone was being used appropriately based on six criteria namely indication for use, dose, frequency of administration, duration of treatment, drug-drug interaction, culture and sensitivity test. The evaluation was made as per the protocol developed from current treatment guidelines. RESULTS: The total of 314 records of patients receiving ceftriaxone was reviewed. The prescribing rate of ceftriaxone was found to be very high (58 % point prevalence). Ceftriaxone use was empiric in 274 (87.3 %) cases. The most common indication for ceftriaxone use was pneumonia; observed in 110 (35.0 %) cases. The most common daily dosage, frequency of administration and duration of treatment with ceftriaxone were 2 g (88.9 %), twice-daily (98.4 %) and 8-14 days (46.2 %), respectively. Inappropriate use of ceftriaxone was observed in most of cases (87.9 %), the greatest proportion of which was attributed to inappropriate frequency of administration (80.3 %), followed by absence of culture and sensitivity test (53.2 %). CONCLUSION: This study revealed that the inappropriate use of ceftriaxone was very high in the medical and emergency wards of Tikur Anbessa Specialized Hospital. This may lead to emergence of resistant pathogens which in turn lead to treatment failure and increased cost of therapy. Therefore, adherence to current evidence-based guidelines is recommended. PMID- 26891695 TI - Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation. AB - A-Raf belongs to the family of oncogenic Raf kinases that are involved in mitogenic signaling by activating the MEK-ERK pathway. Low kinase activity of A Raf toward MEK suggested that A-Raf might have alternative functions. We recently identified A-Raf as a potent inhibitor of the proapoptotic mammalian sterile 20 like kinase (MST2) tumor suppressor pathway in several cancer entities including head and neck, colon, and breast. Independent of kinase activity, A-Raf binds to MST2 thereby efficiently inhibiting apoptosis. Here, we show that the interaction of A-Raf with the MST2 pathway is regulated by subcellular compartmentalization. Although in proliferating normal cells and tumor cells A-Raf localizes to the mitochondria, differentiated non-carcinogenic cells of head and neck epithelia, which express A-Raf at the plasma membrane. The constitutive or induced re localization of A-Raf to the plasma membrane compromises its ability to efficiently sequester and inactivate MST2, thus rendering cells susceptible to apoptosis. Physiologically, A-Raf re-localizes to the plasma membrane upon epithelial differentiation in vivo. This re-distribution is regulated by the scaffold protein kinase suppressor of Ras 2 (KSR2). Downregulation of KSR2 during mammary epithelial cell differentiation or siRNA-mediated knockdown re-localizes A-Raf to the plasma membrane causing the release of MST2. By using the MCF7 cell differentiation system, we could demonstrate that overexpression of A-Raf in MCF7 cells, which induces differentiation. Our findings offer a new paradigm to understand how differential localization of Raf complexes affects diverse signaling functions in normal cells and carcinomas. PMID- 26891698 TI - Retained needle after cement injection during vertebral augmentation and its management strategy. AB - A middle aged patient with multiple myeloma resulting in numerous pathological fractures underwent an L2, L3, and L5 vertebral cement augmentation for pain relief. After injection, the trocar at L2, the final level, could not be withdrawn despite several attempts of needle rotation, a second needle inserted to distract on, and rocking the needle on the pedicle. After a neurosurgical consultation, the patient was transferred to the operating room for open removal. As the needle protruded approximately 3 inches from the patient's back, the patient could not be positioned supine, and was anesthetized and intubated in the right semi-prone position prior to being placed prone on the operating room table. The needle was surgically exposed, cut off at the pedicular bone edge, and its free component was removed. PMID- 26891699 TI - Acute eosinophilic pneumonia. AB - We report the case of an 18-year-old woman who presented to an outside hospital in respiratory distress and was found to have pulmonary eosinophilia. She remained profoundly hypoxaemic despite maximal ventilatory strategies and underwent cannulation for veno-venous extra corporeal membrane oxygenation (ECMO). The respiratory failure improved with time, using corticosteroids, and the veno-venous ECMO helped in stabilisation of the patient in the setting of profound hypoxaemia. PMID- 26891701 TI - Naphtho[2,3-c][1,2,5]thiadiazole and 2H-Naphtho[2,3-d][1,2,3]triazole-Containing D-A-pi-A Conjugated Organic Dyes for Dye-Sensitized Solar Cells. AB - Dipolar dyes comprising an arylamine as the electron donor, a cyanoacrylic acid as electron acceptor, and an electron deficient naphtho[2,3-c][1,2,5]thiadiazole (NTD) or naphtho[2,3-d][1,2,3]triazole (NTz) entity in the conjugated spacer, were developed and used as the sensitizers in dye-sensitized solar cells (DSSCs). The introduction of the NTD unit into the molecular frame distinctly narrows the HOMO/LUMO gap with electronic absorption extending to >650 nm. However, significant charge trapping and dye aggregation were found in these dyes. Under standard global AM 1.5 G illumination, the best cell photovoltaic performance achieved 6.37 and 7.53% (~94% relative to N719-based standard cell) without and with chenodeoxycholic acid (CDCA) coadsorbent, respectively. Without CDCA, the NTz dyes have higher power conversion efficiency (7.23%) than NTD dyes due to less charge trapping, dye aggregation, and better dark current suppression. PMID- 26891702 TI - An Enantioselective Oxidative C-H/C-H Cross-Coupling Reaction: Highly Efficient Method To Prepare Planar Chiral Ferrocenes. AB - A Pd-catalyzed, asymmetric oxidative cross-coupling reaction between ferrocenes and heteroarenes is described. The process, which takes place via a twofold C-H bond activation pathway, proceeds with modest to high efficiencies (36-86%) and high levels of regio- and enantioselectivity (95-99% ee). In the reaction, air oxygen serves as a green oxidant and excess amounts of the coupling partners are not required. The process is the first example of a catalytic asymmetric biaryl coupling reaction that occurs via double C-H bond activation. Finally, the generated coupling products can be readily transformed into chiral ligands and catalysts. PMID- 26891700 TI - Comparison of the TOF-ScanTM acceleromyograph to TOF-Watch SXTM: Influence of calibration. AB - INTRODUCTION: Quantitative neuromuscular monitoring is now widely recommended during anesthesia using neuromuscular blocking agents to prevent postoperative residual paralysis and its related complications. We compared the TOF-Watch SXTM accelerometer requiring initial calibration to the TOF-ScanTM, a new accelerometer with a preset stimulation intensity of 50mA not necessitating calibration. STUDY DESIGN: This pilot, prospective, observational study included adults undergoing general anesthesia with endotracheal intubation and muscle relaxation, having both arms free during surgery. Accelerometers were set up randomly on each arm. Anesthesia was started with remifentanil and propofol before an intubation dose of atracurium or rocuronium. Train of four stimulation was performed every 15s. Differences between measures were tested using Student's t-test and agreement assessed by Bland and Altman analysis. RESULTS: Thirty-two patients were included. During onset, a mean bias of -26seconds with a limit of agreement from -172 to +119seconds was observed between TOF-Watch SXTM and TOF ScanTM to obtain 0 response to TOF. During recovery, TOF-ScanTM showed a significantly later recovery from 1 response to T4/T1>10%, but a bias of 0minute and limits of agreement from -4 to +4minutes for T4/T1>90% (NS). CONCLUSION: These results suggest a poor agreement between the calibrated TOF-Watch SXTM and the fix intensity TOF-ScanTM for onset and early recovery of relaxation (i.e. deep neuromuscular blockade) but a good agreement for recovery to TOF 90%. Data are not interchangeable between the devices, but both can be useful to detect residual paralysis. PMID- 26891704 TI - Cucurbit[8]uril-Containing Multilayer Films for the Photocontrolled Binding and Release of a Guest Molecule. AB - The powerful host-guest chemistry of cucurbit[8]uril (CB[8]) was employed to obtain photoresponsive polyelectrolyte multilayer films for the reversible and photocontrolled binding and release of an organic guest molecule. For this purpose, we designed and synthesized a polyelectrolyte with azobenzene side groups. Then, CB[8] was associated with the azo side group to obtain a supramolecular host-guest complex that was further used as building block in order to prepare photoresponsive and CB[8]-containing polyelectrolyte multilayer films. Ultraviolet spectroscopy and a dissipative quartz crystal microbalance are employed to monitor the formation of the host-guest complex and the layer-by layer self-assembly of the multilayer films, respectively. We demonstrate that the photoresponsive properties of the azo side groups are maintained before and after host-guest complexation with CB[8] in solution and within the multilayer films, respectively. A guest molecule was then specifically included as second binding partner into the CB[8]-containing multilayer films. Subsequently, the release of the guest was performed by UV light irradiation due to the trans-cis isomerization of the adjacent azo side groups. Re-isomerization of the azo side groups was achieved by VIS light irradiation and enabled the rebinding of the guest into CB[8]. Finally, we demonstrate that the photocontrolled binding and release within CB[8]-containing multilayer films can reliably and reversibly be performed over a period of more than 2 weeks with constant binding efficiency. Therefore, we expect such novel type of photosensitive films to have promising future applications in the field of stimuli-responsive nanomaterials. PMID- 26891703 TI - Association of Body Composition With Survival and Locoregional Control of Radiotherapy-Treated Head and Neck Squamous Cell Carcinoma. AB - IMPORTANCE: Major weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy (RT). How baseline and posttreatment body composition affects outcome is unknown. OBJECTIVE: To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control. DESIGN, SETTING, AND PARTICIPANT: Retrospective study of 2840 patients with pathologically proven HNSCC undergoing curative RT at a single academic cancer referral center from October 1, 2003, to August 31, 2013. One hundred ninety patients had computed tomographic (CT) scans available for analysis of skeletal muscle (SM). The effect of pre-RT and post-RT SM depletion (defined as a CT-measured L3 SM index of less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women) on survival and disease control was evaluated. Final follow-up was completed on September 27, 2014, and data were analyzed from October 1, 2014, to November 29, 2015. MAIN OUTCOMES AND MEASURES: Primary outcomes were overall and disease-specific survival and locoregional control. Secondary analyses included the influence of pre-RT body mass index (BMI) and interscan weight loss on survival and recurrence. RESULTS: Among the 2840 consecutive patients who underwent screening, 190 had whole-body positron emission tomography-CT or abdominal CT scans before and after RT and were included for analysis. Of these, 160 (84.2%) were men and 30 (15.8%) were women; their mean (SD) age was 57.7 (9.4) years. Median follow up was 68.6 months. Skeletal muscle depletion was detected in 67 patients (35.3%) before RT and an additional 58 patients (30.5%) after RT. Decreased overall survival was predicted by SM depletion before RT (hazard ratio [HR], 1.92; 95% CI, 1.19-3.11; P = .007) and after RT (HR, 2.03; 95% CI, 1.02-4.24; P = .04). Increased BMI was associated with significantly improved survival (HR per 1-U increase in BMI, 0.91; 95% CI, 0.87-0.96; P < .001). Weight loss without SM depletion did not affect outcomes. Post-RT SM depletion was more substantive in competing multivariate models of mortality risk than weight loss-based metrics (Bayesian information criteria difference, 7.9), but pre-RT BMI demonstrated the greatest prognostic value. CONCLUSIONS AND RELEVANCE: Diminished SM mass assessed by CT imaging or BMI can predict oncologic outcomes for patients with HNSCC, whereas weight loss after RT initiation does not predict SM loss or survival. PMID- 26891707 TI - Effects of boiling and in vitro gastrointestinal digestion on the antioxidant activity of Sonchus oleraceus leaves. AB - Leaves of Sonchus oleraceus L. are especially rich in phenolic compounds and have potent extractable antioxidants. However, it is not known how their antioxidant activity changes after cooking and gastrointestinal digestion. We recorded the profile of phenolics and their associated antioxidant activity in both raw and boiled S. oleraceus leaf extracts after in vitro gastric and intestinal digestion, and quantified their antioxidant potentials using Caco-2 and HepG2 cells. Boiling significantly diminished the oxygen radical absorbance capacity (ORAC) and concentrations of ascorbate and chicoric acid in the soluble fractions. In contrast, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and concentrations of caftaric and chlorogenic acids were unaffected. Phenolics in the soluble fraction were absorbed into cultured human cells and exerted antioxidant activity. Only chlorogenic acid content remained stable during gastrointestinal digestion. S. oleraceus appears to be an excellent dietary source of phenolic antioxidants. PMID- 26891706 TI - Finite sample pointwise confidence intervals for a survival distribution with right-censored data. AB - We review and develop pointwise confidence intervals for a survival distribution with right-censored data for small samples, assuming only independence of censoring and survival. When there is no censoring, at each fixed time point, the problem reduces to making inferences about a binomial parameter. In this case, the recently developed beta product confidence procedure (BPCP) gives the standard exact central binomial confidence intervals of Clopper and Pearson. Additionally, the BPCP has been shown to be exact (gives guaranteed coverage at the nominal level) for progressive type II censoring and has been shown by simulation to be exact for general independent right censoring. In this paper, we modify the BPCP to create a 'mid-p' version, which reduces to the mid-p confidence interval for a binomial parameter when there is no censoring. We perform extensive simulations on both the standard and mid-p BPCP using a method of moments implementation that enforces monotonicity over time. All simulated scenarios suggest that the standard BPCP is exact. The mid-p BPCP, like other mid p confidence intervals, has simulated coverage closer to the nominal level but may not be exact for all survival times, especially in very low censoring scenarios. In contrast, the two asymptotically-based approximations have lower than nominal coverage in many scenarios. This poor coverage is due to the extreme inflation of the lower error rates, although the upper limits are very conservative. Both the standard and the mid-p BPCP methods are available in our bpcp R package. Published 2016. This article is US Government work and is in the public domain in the USA. PMID- 26891705 TI - Activation of the TGFbeta pathway impairs endothelial to haematopoietic transition. AB - The endothelial to haematopoietic transition (EHT) is a key developmental process where a drastic change of endothelial cell morphology leads to the formation of blood stem and progenitor cells during embryogenesis. As TGFbeta signalling triggers a similar event during embryonic development called epithelial to mesenchymal transition (EMT), we hypothesised that TGFbeta activity could play a similar role in EHT as well. We used the mouse embryonic stem cell differentiation system for in vitro recapitulation of EHT and performed gain and loss of function analyses of the TGFbeta pathway. Quantitative proteomics analysis showed that TGFbeta treatment during EHT increased the secretion of several proteins linked to the vascular lineage. Live cell imaging showed that TGFbeta blocked the formation of round blood cells. Using gene expression profiling we demonstrated that the TGFbeta signalling activation decreased haematopoietic genes expression and increased the transcription of endothelial and extracellular matrix genes as well as EMT markers. Finally we found that the expression of the transcription factor Sox17 was up-regulated upon TGFbeta signalling activation and showed that its overexpression was enough to block blood cell formation. In conclusion we showed that triggering the TGFbeta pathway does not enhance EHT as we hypothesised but instead impairs it. PMID- 26891708 TI - [Care pathways of cancer patients: Modeling and risks analysis induced by oral anticancer drugs]. AB - The care pathway of cancer patients is complex and therefore difficult to define. The oral anticancers (AKPO) have shown their benefits to patients and health professionals, however, the risks induced on the care pathway remain unknown. The objective of the study is to define, quantify the risks from AKPO and their effects on the care pathway (breakdown [Ds], rupture [Rt]). From the proposed care pathway model, FMEA method is used to analyze risks. For the 3 identified processes (1 monotherapy, 2 bitherapies: 2 AKPO or 1 AKPO/1 AKIV), analysis revealed an average of 91 risks, 173 Ds, 147 Rt, increased for 1 AKPO/1 AKIV therapy. The administration and delivery are the most risky steps. The lack of training and information of patients and healthcare professionals generates 80% of Ds and Rt. This model confirms the complexity, variability of the care pathway. The development of actions to improve town-hospital coordination and exchange of information is required to optimize and secure the route, confirming the objectives of "Plan Cancer 3". PMID- 26891709 TI - Migraineurs Initially Visiting the Gastroenterology Department. AB - BACKGROUND AND OBJECTIVES: Migraine-related nausea and vomiting are usually associated with severe and debilitating headache. However, there are unique headache patients with a chief complaint of prominent gastrointestinal (GI) discomfort, instead of headache. We sought to investigate distinctive characteristics and clinical outcomes of such patients, compared to migraine patients initially visiting headache clinic. METHODS: This was a retrospective case-control study using a headache registry from April 2012 to December 2013. Case subjects were defined as patients who had first visited the gastroenterology clinic with chief complaint of nausea and/or vomiting, but then referred to the headache clinic for evaluation and management of concurrent headache. They were 1:2 matched to control subjects who met the migraine criteria based on propensity scores adjusted for age, sex, aura, headache frequency, and headache intensity. RESULTS: We identified 51 case subjects, of which 80.4% were compatible with the migraine criteria. In multivariate testing, the case subjects were inversely associated with family history of headache (odds ratios [OR]: 0.36, 95% confidence interval [CI]: 0.13-0.99), alcohol drinking (OR: 0.18, 95% CI: 0.05 0.69), and aggravation by physical activity (OR: 0.19, 95% CI: 0.08-0.43). The proportions of subjects with a favorable clinical outcome in migraine management did not differ between the case and control groups (82.2% vs 79.1%, P = .670). CONCLUSIONS: Primary symptoms of the case subjects had been GI; however, migraine management was most effective in relieving both prominent GI discomfort and headache. Our findings suggest that physicians should consider and investigate for the presence of migraine in patients with prominent GI symptoms and concurrent headache. PMID- 26891710 TI - Brain imaging demonstrates a reduced neural impact of eating in obesity. AB - OBJECTIVE: This study investigated functional brain response differences to food in women with BMI either <25 kg/m(2) (lean) or >35 kg/m(2) (severe obesity). DESIGN AND METHODS: Thirty women, 18-65 years old, from academic medical centers participated. Baseline brain perfusion was measured with arterial spin labeling. Brain activity was measured via blood-oxygen-level-dependent functional magnetic resonance imaging in response to food cues, and appeal to cues was rated. Subjective hunger/fullness was reported pre- and post-imaging. After a standard meal, measures were repeated. RESULTS: When fasting, brain perfusion did not differ significantly between groups; and both groups showed significantly increased activity in the neo- and limbic cortices and midbrain compared with baseline (P < 0.05, family-wise-error whole-brain corrected). Once fed, the lean group showed significantly decreased activation in these areas, especially the limbic cortex, whereas the group with severe obesity showed no such decreases (P < 0.05, family-wise-error whole-brain corrected). After eating, appeal ratings of food decreased only in lean women. Within groups, hunger decreased (P < 0.001) and fullness increased (P < 0.001) fasted to fed. CONCLUSIONS: While fasting, brain response to food cues in women did not differ significantly despite BMI. After eating, brain activity quickly diminished in lean women but remained elevated in women with severe obesity. These brain activation findings confirm previous studies. PMID- 26891711 TI - Impact of left ventricular function on clinical outcomes of functional mitral regurgitation patients undergoing transcatheter mitral valve repair. AB - OBJECTIVES: To evaluate the impact of baseline left ventricular (LV) function on the clinical outcomes of patients with functional mitral regurgitation (FMR) treated with MitraClip. BACKGROUND: It is unknown whether patients with significant FMR and severe LV dysfunction benefit from MitraClip. METHODS: A cohort of 77 patients with significant FMR undergoing MitraClip procedure between December 2010 and January 2015 was categorized by baseline LV ejection fraction (LVEF) into tertiles: LVEF <27% (n = 27), LVEF 27-37% (n = 25), and LVEF >37% (n = 25). We sought to evaluate the impact of LVEF on all-cause mortality at follow up. RESULTS: There were no significant differences in baseline comorbidities, medical treatment and MR severity among tertiles of LVEF. Overall procedural success was 94%, with no differences among groups (LVEF <27%: 89%; LVEF 27-37%: 100%; LVEF >37%: 92%; P = 0.25). Median follow-up was 372 days (interquartile range: 128-627 days). MR severity improved in all three groups, as compared to baseline. There were no differences in the prevalence of MR <=2+ on follow-up (P = 0.40). Mortality was highest in patients with LVEF <27% (41%), as compared with LVEF 27-37% (16%) and LVEF >37% (4%), P = 0.004. Patient who died had a lower baseline LVEF compared to those who survived (24.8 +/- 7.7% versus 35.5 +/- 13.7%, P < 0.001). An LVEF <27% was an independent predictor of mortality after adjusting for procedural success: hazard ratio 3.4 (95% CI: 1.1 to 10.0; P = 0.030). CONCLUSIONS: MitraClip is effective in FMR patients regardless of the severity of LV dysfunction. However, low baseline LVEF is associated with increased mortality, despite procedural success. (c) 2016 Wiley Periodicals, Inc. PMID- 26891712 TI - Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells. AB - Hepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. Infection usually leads to acute hepatitis that can become fulminant, particularly among pregnant women and in patients with preexisting liver disease, or may evolve to a chronic state, especially in immunosuppressed individuals. HEV has been shown to produce a range of extra-hepatic manifestations including aplastic anaemia, acute thyroiditis, glomerulonephritis as well as neurological disorders such as Guillain-Barre syndrome, neuralgic amyotrophy and encephalitis. The pathogenesis of these neurological injuries remains largely unknown, and it is also uncertain whether or not HEV can directly infect neuronal cells. In this study, we investigated whether HEV is capable of completing the viral life cycle in human neuronal-derived cell lines such as neuroepithelioma (SK-N-MC), desmoplastic cerebellar medulloblastoma (DAOY), glioblastoma multiforme (DBTRG), glioblastoma astrocytoma (U-373 MG) and oligodendrocytic (M03.13) cells. Following transfection of these cells with HEV Gaussia luciferase reporter virus, all tested cell lines supported HEV RNA replication. Furthermore, extra- and intracellular viral capsid was detected by an HEV antigen ELISA as a marker for virus assembly and release. Permissiveness for HEV cell entry could be demonstrated for the oligodendrocytic cell line M03.13. In conclusion, these results indicate that HEV tropism is not restricted to the liver and HEV can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurologic disorders during HEV infection. PMID- 26891714 TI - Genetic determinants of cardiometabolic risk factors in rural families in Brazil. AB - OBJECTIVES: The purpose of this study was to estimate the heritability of genetic and environmental correlations between cardiometabolic risk factors in extended pedigrees. METHODS: The Jequitinhonha Community Family Study Cohort (JCFSC) consists of individuals aged >=18 years living in rural villages. Family pedigrees were constructed of the cohort. The following data were collected: demographic and socioeconomic status, lifestyle variables, anthropometrics, and lipid traits. RESULTS: The JCFSC consists of 931 individuals distributed into 69 pedigrees with 4,907 members in total. The heritabilities were 0.47 for total cholesterol (TC), 0.44 for triglycerides (TG) and 0.42 for high-density lipoprotein cholesterol (HDLc), 0.49 for metabolic syndrome, approximately 0.60 for anthropometric traits and 0.30 for blood pressure/hypertension. Significant genetic correlations (rhog ) were found mainly between TG and TC (rhog = 0.58) and hypertension and TG (rhog = 0.52). Systolic blood pressure (SBP) was correlated with TG (rhog = 0.39) and HDLc (rhog = -0.30). Diastolic blood pressures correlated with TG (rhog =0.56) and TC (rhog =0.30). Genetic correlations were also found between anthropometric traits, including: body mass index (BMI) and TG (rhog =0.34), waist circumference (WC) and TG (rhog =0.42), and WC and HDLc (rhog =-0.33). Household effects were found for HDLc (c(2) = 0.19), SBP (c(2) = 0.14) and Hypertension (c(2) = 0.14). CONCLUSIONS: To some phenotypes, including lipids, hypertension, blood pressure, and anthropometric traits, genetic contribution is important in the determination of cardiometabolic risk factors. This study provides a foundation for future studies. These will mainly focus on rare variants that could describe the genetic mechanisms influencing cardiometabolic risk. Am. J. Hum. Biol. 28:619-626, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26891715 TI - Nonmotor symptoms in patients without evidence of dopaminergic deficit. PMID- 26891716 TI - The ambulatory hypotensive effect of aerobic training: a reappraisal through a meta-analysis of selected moderators. AB - The effectiveness of regular exercise in decreasing both systolic and diastolic blood pressure (BP) is well-established. Our purpose was to assess the impact of both subject and physical activity program characteristics on ambulatory BP through a meta-analysis of the existing literature. Three databases (PubMed, Embase, Web of Science) were searched using relevant terms and strategies. From 637 identified records, 37 studies met inclusion criteria: details about training intervention and participant characteristics, pre- and post-training ambulatory BP measurements, at home (HBPM) or during 24-h (ABPM). The weighted mean difference was for 24-h systolic/diastolic ABPM (n = 847 participants): -4.06/ 2.77 mmHg (95%CI: -5.19 to -2.93/-3.58 to -1.97; P < 0.001), for daytime (ABPM or HBPM, n = 983): -3.78/-2.73 mmHg (95%CI: -5.09 to -2.47/-3.57 to -1.89; P < 0.001) and nighttime ABPM periods (n = 796): -2.35/-1.70 mmHg (95%CI: -3.26 to 1.44/-2.45 to -0.95; P < 0.001). Characteristics significantly influencing BP improvement were: an initial office BP >=130/85 mmHg and diet-induced weight loss. We found no differences according to sex, age, or training characteristics (intensity, number of sessions, training duration). Antihypertensive effects of aerobic training assessed by ambulatory BP measurements appear significant and clinically relevant for both daytime and nighttime periods, in particular for participants with an office BP >=130/85 mmHg. PMID- 26891713 TI - High frequency of +1 programmed ribosomal frameshifting in Euplotes octocarinatus. AB - Programmed -1 ribosomal frameshifting (-1 PRF) has been identified as a mechanism to regulate the expression of many viral genes and some cellular genes. The slippery site of -1 PRF has been well characterized, whereas the +1 PRF signal and the mechanism involved in +1 PRF remain poorly understood. Previous study confirmed that +1 PRF is required for the synthesis of protein products in several genes of ciliates from the genus Euplotes. To accurately assess the frequency of genes requiring frameshift in Euplotes, the macronuclear genome and transcriptome of Euplotes octocarinatus were analyzed in this study. A total of 3,700 +1 PRF candidate genes were identified from 32,353 transcripts, and the gene products of these putative +1 PRFs were mainly identified as protein kinases. Furthermore, we reported a putative suppressor tRNA of UAA which may provide new insights into the mechanism of +1 PRF in euplotids. For the first time, our transcriptome-wide survey of +1 PRF in E. octocarinatus provided a dataset which serves as a valuable resource for the future understanding of the mechanism underlying +1 PRF. PMID- 26891717 TI - A simple approach for an optically transparent nanochannel device prototype. AB - Compared with microfluidic devices, the fabrication of structure-controllable and designable nanochannel devices has been considered to have high costs and complex procedures, which require expensive equipment and high-quality raw materials. Exploring fast, simple and inexpensive approaches in nanochannel fabrication will be greatly helpful to speed up laboratory studies of nanofluidics. Here we developed a simple and inexpensive approach to fabricate a nanochannel device with a glass/epoxy resin/glass structure. The grooves were engraved using a UV laser on an aluminum sacrificial layer on the substrate glass, and epoxy resin was coated on the substrate and stuffed fully into the grooves. Another glass plate with holes for fluidic inlets and outlets was bonded on the top of the resin layer. The nanochannels were formed by etching thin sacrificial layers electrochemically. Meanwhile, the microstructures of the fluidic outlets and inlets could be fabricated simultaneously to the nanochannel formation. The total processing time for the simple nanochannel device took less than 10 hours. Optically transparent nanochannels with a depth of up to 20 nm were achieved. Nanofluidic behaviors in the nanochannels were observed under both optical and fluorescence microscopes. PMID- 26891719 TI - The Influence of Psychological and Lifestyle Factors on the Reporting of Postconcussion-Like Symptoms. AB - Self-reported symptoms are an integral part of the assessment and management of a sports-related concussion. However, postconcussion-like symptoms are reported by non-concussed individuals. Moreover, the current best practice in the reporting of symptoms does not take into account the potential influence of psychological and lifestyle factors. This study aimed to explore the influence of these factors on the reporting of postconcussion-like symptoms. University students (N= 603) completed the Sport Concussion Assessment Tool 2 postconcussion symptom scale along with other predictor variables via a cross-sectional web-based survey. Linear regression analyses revealed six modifiers contributing to the total symptom score with the strongest being alcohol consumption (Estimate = 2.75, p < .001). Following these findings, clinicians need to exercise caution when interpreting the symptom scores for making decisions on the return-to-play (RTP). A failure to do so may lead the health professional to either prematurely RTP or not clear the concussed athlete to resume their sport. PMID- 26891718 TI - The use of purposeful sampling in a qualitative evidence synthesis: A worked example on sexual adjustment to a cancer trajectory. AB - BACKGROUND: An increasing number of qualitative evidence syntheses papers are found in health care literature. Many of these syntheses use a strictly exhaustive search strategy to collect articles, mirroring the standard template developed by major review organizations such as the Cochrane and Campbell Collaboration. The hegemonic idea behind it is that non-comprehensive samples in systematic reviews may introduce selection bias. However, exhaustive sampling in a qualitative evidence synthesis has been questioned, and a more purposeful way of sampling papers has been proposed as an alternative, although there is a lack of transparency on how these purposeful sampling strategies might be applied to a qualitative evidence synthesis. We discuss in our paper why and how we used purposeful sampling in a qualitative evidence synthesis about 'sexual adjustment to a cancer trajectory', by giving a worked example. METHODS: We have chosen a mixed purposeful sampling, combining three different strategies that we considered the most consistent with our research purpose: intensity sampling, maximum variation sampling and confirming/disconfirming case sampling. RESULTS: The concept of purposeful sampling on the meta-level could not readily been borrowed from the logic applied in basic research projects. It also demands a considerable amount of flexibility, and is labour-intensive, which goes against the argument of many authors that using purposeful sampling provides a pragmatic solution or a short cut for researchers, compared with exhaustive sampling. Opportunities of purposeful sampling were the possible inclusion of new perspectives to the line-of-argument and the enhancement of the theoretical diversity of the papers being included, which could make the results more conceptually aligned with the synthesis purpose. CONCLUSIONS: This paper helps researchers to make decisions related to purposeful sampling in a more systematic and transparent way. Future research could confirm or disconfirm the hypothesis of conceptual enhancement by comparing the findings of a purposefully sampled qualitative evidence synthesis with those drawing on an exhaustive sample of the literature. PMID- 26891720 TI - Normative Data of the Montreal Cognitive Assessment in the Greek Population and Parkinsonian Dementia. AB - The Montreal Cognitive Assessment (MoCA) is a brief cognitive instrument for the measurement of dementia. The aim of the present study is to provide normative data for the MoCA test in the Greek speaking population and to measure its validity in a clinical group of parkinsonian dementia participants. A total of 710 healthy Greek speaking participants and 19 parkinsonian dementia participants took part in the study. Both, the MoCA test and a neuropsychological test battery (digit span, semantic verbal fluency, phonemic verbal fluency, Color Trails Test) were administered to the normative and clinical samples. The test was found to correlate with all neuropsychological tests used in the test battery and it showed high discriminant validity (optimal screening cutoff point = 21, sensitivity = 0.82, specificity = 0.90) in the parkinsonian dementia participants. Further research is needed to use it in larger clinical samples and in different neurological diseases. PMID- 26891721 TI - The thorax of the cave cricket Troglophilus neglectus: anatomical adaptations in an ancient wingless insect lineage (Orthoptera: Rhaphidophoridae). AB - BACKGROUND: Secondary winglessness is a common phenomenon found among neopteran insects. With an estimated age of at least 140 million years, the cave crickets (Rhaphidophoridae) form the oldest exclusively wingless lineage within the long horned grasshoppers (Ensifera). With respect to their morphology, cave crickets are generally considered to represent a 'primitive' group of Ensifera, for which no apomorphic character has been reported so far. RESULTS: We present the first detailed investigation and description of the thoracic skeletal and muscular anatomy of the East Mediterranean cave cricket Troglophilus neglectus (Ensifera: Rhaphidophoridae). T. neglectus possesses sternopleural muscles that are not yet reported from other neopteran insects. Cave crickets in general exhibit some unique features with respect to their thoracic skeletal anatomy: an externally reduced prospinasternum, a narrow median sclerite situated between the meso- and metathorax, a star-shaped prospina, and a triramous metafurca. The thoracic muscle equipment of T. neglectus compared to that of the bush cricket Conocephalus maculatus (Ensifera: Tettigoniidae) and the house cricket Acheta domesticus (Ensifera: Gryllidae) reveals a number of potentially synapomorphic characters between these lineages. CONCLUSIONS: Based on the observed morphology we favor a closer relationship of Rhaphidophoridae to Tettigoniidae rather than to Gryllidae. In addition, the comparison of the thoracic morphology of T. neglectus to that of other wingless Polyneoptera allows reliable conclusions about anatomical adaptations correlated with secondary winglessness. The anatomy in apterous Ensifera, viz. the reduction of discrete direct and indirect flight muscles as well as the strengthening of specific leg muscles, largely resembles the condition found in wingless stick insects (Euphasmatodea), but is strikingly different from that of other related wingless insects, e.g. heel walkers (Mantophasmatodea), ice crawlers (Grylloblattodea), and certain grasshoppers (Caelifera). The composition of direct flight muscles largely follows similar patterns in winged respectively wingless species within major polyneopteran lineages, but it is highly heterogeneous between those lineages. PMID- 26891722 TI - The impact of retirement on health: quasi-experimental methods using administrative data. AB - BACKGROUND: Is retirement good or bad for health? Disentangling causality is difficult. Much of the previous quasi-experimental research on the effect of health on retirement used self-reported health and relied upon discontinuities in public retirement incentives across Europe. The current study investigated the effect of retirement on health by exploiting discontinuities in private retirement incentives to test the effect of retirement on health using a quasi experimental study design. METHODS: Secondary data (1997-2009) on a cohort of male manufacturing workers in a United States setting. Health status was determined using claims data from private insurance and Medicare. Analyses used employer-based administrative and claims data and claim data from Medicare. RESULTS: Widely used selection on observables models overstate the negative impact of retirement due to the endogeneity of the decision to retire. In addition, health status as measured by administrative claims data provide some advantages over the more commonly used survey items. Using an instrument and administrative health records, we find null to positive effects from retirement on all fronts, with a possible exception of increased risk for diabetes. CONCLUSIONS: This study provides evidence that retirement is not detrimental and may be beneficial to health for a sample of manufacturing workers. In addition, it supports previous research indicating that quasi-experimental methodologies are necessary to evaluate the relationship between retirement and health, as any selection on observable model will overstate the negative relationship of retirement on health. Further, it provides a model for how such research could be implemented in countries like the United States that do not have a strong public pension program. Finally, it demonstrates that such research need-not rely upon survey data, which has certain shortcomings and is not always available for homogenous samples. PMID- 26891723 TI - Dual-specificity phosphatase 14 protects the heart from aortic banding-induced cardiac hypertrophy and dysfunction through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. AB - Dual-specificity phosphatase 14 (Dusp14), an important negative modulator of mitogen-activated protein kinase (MAPK) signaling pathways, has been implicated in inflammatory immune response, cancers, cell differentiation and proliferation. The role of Dusp14 in chronic pressure overload-induced cardiac hypertrophy has not been explored. Here we have shown that Dusp14-/- knockout mice and cardiac specific Dusp14 transgenic mice were generated and subjected to aortic banding (AB) for 4 weeks. Our results demonstrated that genetic loss of Dusp14 significantly aggravated cardiac hypertrophy, fibrosis, ventricular dilation and dysfunction, whereas transgenic cardiac-specific Dusp14 overexpression significantly attenuated AB-induced cardiac dysfunction and remodeling. In vitro, adenoviral overexpression of constitutive Dusp14 blocked angiotensin II-induced hypertrophic growth of cardiomyocytes, while Dusp14 knockdown led to opposite effects. Mechanistically, excessive phosphorylation of TAK1, P38MAPK and JNK1/2 was evidenced in Dusp14-/- knockout mice post-AB and inactivation of TAK1-P38MAPK and -JNK1/2 signaling using TAK1 inhibitor 5Z-7-ox shares similar antihypertrophic effect as Dusp14 overexpression. Moreover, we show that Dusp14 directly interacted with TAK1. Results from present experiments indicate that Dusp14 protects the heart from AB-induced cardiac hypertrophy and dysfunction possibly through inactivation of TAK1-P38MAPK/-JNK1/2 signaling pathway. Future studies are warranted to test the feasibility of overexpressing Dusp14 as a therapeutic strategy to attenuate cardiac hypertrophy and failure. PMID- 26891725 TI - Current Controversies in Radiofrequency Ablation Therapy for Barrett's Esophagus. AB - OPINION STATEMENT: Barrett's esophagus (BE) is the most important risk factor for esophageal adenocarcinoma. Through the sequence of no dysplasia to low-grade dysplasia (LGD) and high-grade dysplasia (HGD), eventually early cancer (EC) may develop. The risk of neoplastic progression is relatively low, 0.5-0.9 % per patient per year. However, once diagnosed, esophageal adenocarcinoma is often irresectable, and 5-year survival is only 15 %. Therefore, non-dysplastic BE patients are kept under endoscopic surveillance to detect early neoplasia in a curable stage. In case of LGD confirmed by an expert pathologist, risk of neoplastic progression is high. In these confirmed LGD patients, prophylactic ablation using radiofrequency ablation (RFA) of the Barrett's segment has proven to significantly reduce risk of neoplastic progression. Once patients are diagnosed with HGD or EC, they have a clear indication for endoscopic treatment. The cornerstone for endoscopic management of early Barrett's neoplasia is endoscopic resection of mucosal abnormalities. Endoscopic resection (ER) provides a large tissue specimen for accurate histological evaluation to select those patients for further endoscopic management, who have neoplasia limited to the mucosa, well to moderately differentiated and without lymph-vascular invasion. After ER, the remainder of the Barrett's mucosa can be eradicated with RFA, to prevent occurrence of metachronous lesions. PMID- 26891726 TI - Renal failure from birth-AKI or CKD? Questions. AB - A case is presented of a neonate born at 32 weeks of gestation with intra-uterine growth retardation. The renal scan performed at 31 weeks showed oligohydramnios but normal kidneys. The neonate was oliguric from birth and required early peritoneal dialysis. Her urine showed heavy proteinuria, and the plasma albumin was very low. Post-natal ultrasonography showed large bright kidneys with reduced corticomedullary differentiation but no dysplastia; arterial and venous flow was normal on Doppler ultrasound. The quiz discusses the differential diagnosis with particular reference to whether this picture represents acute kidney injury with expected improvement or chronic kidney disease. Further questions discuss mechanisms of renal failure in this situation. Finally, with reference to previous case reports and series, a correlation between a specific mutation and this severe phenotype is proposed. PMID- 26891724 TI - Atheroprotection through SYK inhibition fails in established disease when local macrophage proliferation dominates lesion progression. AB - Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6C(high) monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participate in downstream signaling of various receptors that mediate these processes. We tested the effect of the SYK inhibitor fostamatinib on hypercholesterolemia-associated myelopoiesis and plaque formation in Apoe(-/-) mice during early and established atherosclerosis. Mice consuming a high cholesterol diet supplemented with fostamatinib for 8 weeks developed less atherosclerosis. Histologic and flow cytometric analysis of aortic tissue showed that fostamatinib reduced the content of Ly6C(high) monocytes and macrophages. SYK inhibition limited Ly6C(high) monocytosis through interference with GM-CSF/IL 3 stimulated myelopoiesis, attenuated cell adhesion to the intimal surface, and blocked M-CSF stimulated monocyte to macrophage differentiation. In Apoe(-/-) mice with established atherosclerosis, however, fostamatinib treatment did not limit macrophage accumulation or lesion progression despite a significant reduction in blood monocyte counts, as lesional macrophages continued to proliferate. Thus, inhibition of hypercholesterolemia-associated monocytosis, monocyte infiltration, and differentiation by SYK antagonism attenuates early atherogenesis but not established disease when local macrophage proliferation dominates lesion progression. PMID- 26891727 TI - Renal failure from birth-AKI or CKD? Answers. PMID- 26891728 TI - Significance of Programmed Death Ligand 1 (PD-L1) Immunohistochemical Expression in Colorectal Cancer. AB - INTRODUCTION: The significance of programmed death ligand 1 (PD-L1) expression in the prognosis of patients with colorectal cancer remains to be determined. METHODS: We assessed the levels of PD-L1 expression in tumor-infiltrating immune cells as well as tumor cells, and evaluated the association between PD-L1 expression and clinical outcome in 262 colorectal cancer patients. RESULTS: In univariate analysis, TNM stage (p < 0.001), PD-L1 expression in tumor infiltrating immune cells (p = 0.016), tumor location (p = 0.033), and tumor size (p = 0.019) were associated with survival. In multivariate analysis, PD-L1 expression in tumor infiltrating immune cells and TNM stage were independent prognostic factors (HR 1.83, 95 % CI 1.09-3.05, p = 0.021; HR 2.49, 95 % CI 1.51 4.12, p < 0.001, respectively). Eight percent of patients had positive PD-L1 expression in tumor cells. In contrast, PD-L1 expression in tumor cells was not significantly associated with patient clinical outcome. CONCLUSIONS: Our data indicate that PD-L1 status in tumor-infiltrating immune cells is a significant prognostic factor in colorectal cancer patients. There is a need for randomized studies that evaluate the role of PD-L1 expression in colorectal cancer in treatment decision protocols for novel immunotherapy. PMID- 26891729 TI - therascreen(r) EGFR RGQ PCR Kit: A Companion Diagnostic for Afatinib and Gefitinib in Non-Small Cell Lung Cancer. AB - therascreen((r)) EGFR RGQ PCR Kit is a real-time polymerase chain reaction test kit for the qualitative detection of exon 19 deletions and L858R mutation of the human EGFR gene in formalin-fixed paraffin-embedded non-small cell lung cancer (NSCLC) tissue. The US FDA has approved the kit for selecting patients with NSCLC for treatment with afatinib or gefitinib. The test has good analytical sensitivity and specificity. It requires only two 5 um tissue sections, is easy to use, provides automated interpretation of results and can be performed in <8 h. There is good concordance between EGFR mutation test results obtained with this kit and several other assays. The clinical utility of the kit has been validated in phase 3 or 4 trials in which NSCLC patients with EGFR mutations as detected by the kit had greater clinical benefits with afatinib or gefitinib than with standard chemotherapy. PMID- 26891731 TI - Impact of Prothrombotic Risk Factors in a Cohort of Egyptian Hemophilia A Patients. AB - INTRODUCTION: Hemophilias are a group of related bleeding disorders that show an X-linked pattern of inheritance. The clinical phenotype of severe hemophilia may vary markedly among patients as a result of many factors, including genetic prothrombotic risk factors. OBJECTIVES: Our objective was to study the incidence of the most common prothrombotic risk factors for additive effects among Egyptian patients with hemophilia A and their impact on clinical phenotype; annual bleeding frequency and severity of hemophilic arthropathy, as well as the effect of a single variation in these patients. METHODS: This study was carried out in 100 patients with hemophilia A. Genotyping for factor V Leiden (FVL) G1691A, prothrombin G20210A, MTHFR C677T, and A1298C mutations was conducted using a real time-polymerase chain reaction (RT-PCR) assay. RESULTS: Our study revealed mutations in hemophilia patients as follows: prothrombin G20210A (3 %), FVL (14 %), MTHFR C677T (42 %), and A1298C (59 %). Despite a lack of statistical significance when each gene was analysed separately, heterozygosity of prothrombin G20210A or FVL was always associated with either a mild or moderate, but never a severe, clinical presentation. The lowest bleeding frequency (less than once per month) was identified among patients with two heterozygous variants irrespective of the involved genes. In addition, the incidence of hemarthrosis was significantly higher among patients with a wild genotype of the prothrombin gene and FVL, and the average number of affected joints was significantly higher among patients with wild-type prothrombin and FVL genes than among heterozygous patients. CONCLUSION: These prothrombotic mutations have a cumulative effect in amelioration of the severity of bleeding in hemophiliacs. The most prominent effect is that of prothrombin G20210A and FVL, while MTHFR C677A and A1298C gene mutations are less conclusive. PMID- 26891730 TI - miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development. AB - Breast cancer (BC) is a heterogeneous disease that develops into a large number of varied phenotypes. One of the features used in its classification and therapy selection is invasiveness. MicroRNA-21 (miR-21) is considered to be an important element of BC invasiveness, and miR-21 levels are frequently increased in different tumor types compared with normal tissue, including the breast. Experimental and literature research has highlighted that miR-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. The main goal of this research was to specify the predominant role of miR-21 in the different phases of BC pathogenesis, i.e. whether it was involved in the early (initiation), later (promotion), or late (propagation, progression) phases. Our second goal was to explain the roles of miR-21 targets in BC by an in silico approach and literature review, and to associate the importance of miR-21 with particular phases of BC pathogenesis through the action of its target genes. Analysis has shown that changes in miR-21 levels might be important for the later and/or late phases of breast cancerogenesis rather than for the initial early phases. Targets of miR-21 (TIMP3, PDCD4, PTEN, TPM1 and RECK) are also primarily involved in BC promotion and progression, especially invasion, angiogenesis and metastasis. miR-21 expression levels could perhaps be used in conjunction with the standard diagnostic parameters as an indicator of BC presence, and to indicate a phenotype likely to show early invasion/metastasis detection and poor prognosis. PMID- 26891732 TI - Miniaturization Technologies for Efficient Single-Cell Library Preparation for Next-Generation Sequencing. AB - As the cost of next-generation sequencing has decreased, library preparation costs have become a more significant proportion of the total cost, especially for high-throughput applications such as single-cell RNA profiling. Here, we have applied novel technologies to scale down reaction volumes for library preparation. Our system consisted of in vitro differentiated human embryonic stem cells representing two stages of pancreatic differentiation, for which we prepared multiple biological and technical replicates. We used the Fluidigm (San Francisco, CA) C1 single-cell Autoprep System for single-cell complementary DNA (cDNA) generation and an enzyme-based tagmentation system (Nextera XT; Illumina, San Diego, CA) with a nanoliter liquid handler (mosquito HTS; TTP Labtech, Royston, UK) for library preparation, reducing the reaction volume down to 2 uL and using as little as 20 pg of input cDNA. The resulting sequencing data were bioinformatically analyzed and correlated among the different library reaction volumes. Our results showed that decreasing the reaction volume did not interfere with the quality or the reproducibility of the sequencing data, and the transcriptional data from the scaled-down libraries allowed us to distinguish between single cells. Thus, we have developed a process to enable efficient and cost-effective high-throughput single-cell transcriptome sequencing. PMID- 26891733 TI - Early identification of cerebrovascular events in patients presenting with vertigo or dizziness. PMID- 26891734 TI - Specific autoantigens in experimental autoimmunity-associated atherosclerosis. AB - Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated atherosclerosis by transplanting bone marrow from FcgammaRIIB knockout (FcRIIB(-/-)) mice into LDL receptor knockout mice. We characterized the cellular and molecular mechanisms of atherogenesis and identified specific aortic autoantigens using serologic proteomic studies. En face lesion area analysis showed more aggressive atherosclerosis in autoimmune mice compared with control mice (0.64 +/- 0.12 vs 0.32 +/- 0.05 mm(2); P < 0.05, respectively). At the cellular level, FcRIIB(-/-) macrophages showed significant reduction (46-72%) in phagocytic capabilities. Proteomic analysis revealed circulating autoantibodies in autoimmune mice that targeted 25 atherosclerotic lesion proteins, including essential components of adhesion complex, cytoskeleton, and extracellular matrix, and proteins involved in critical functions and pathways. Microscopic examination of atherosclerotic plaques revealed essential colocalization of autoantibodies with endothelial cells, their adherence to basement membranes, the internal elastica lamina, and necrotic cores. The new vascular autoimmunosome may be a useful target for diagnostic and immunotherapeutic interventions in autoimmunity-associated diseases that have accelerated atherosclerosis.-Merched, A. J., Daret, D., Li, L., Franzl, N., Sauvage-Merched, M. Specific autoantigens in experimental autoimmunity-associated atherosclerosis. PMID- 26891735 TI - Chronic exposure to air pollution particles increases the risk of obesity and metabolic syndrome: findings from a natural experiment in Beijing. AB - Epidemiologic evidence suggests that air pollution is a risk factor for childhood obesity. Limited experimental data have shown that early-life exposure to ambient particles either increases susceptibility to diet-induced weight gain in adulthood or increases insulin resistance, adiposity, and inflammation. However, no data have directly supported a link between air pollution and non-diet-induced weight increases. In a rodent model, we found that breathing Beijing's highly polluted air resulted in weight gain and cardiorespiratory and metabolic dysfunction. Compared to those exposed to filtered air, pregnant rats exposed to unfiltered Beijing air were significantly heavier at the end of pregnancy. At 8 wk old, the offspring prenatally and postnatally exposed to unfiltered air were significantly heavier than those exposed to filtered air. In both rat dams and their offspring, after continuous exposure to unfiltered air we observed pronounced histologic evidence for both perivascular and peribronchial inflammation in the lungs, increased tissue and systemic oxidative stress, dyslipidemia, and an enhanced proinflammatory status of epididymal fat. Results suggest that TLR2/4-dependent inflammatory activation and lipid oxidation in the lung can spill over systemically, leading to metabolic dysfunction and weight gain.-Wei, Y., Zhang, J., Li, Z., Gow, A., Chung, K. F., Hu, M., Sun, Z., Zeng, L., Zhu, T., Jia, G., Li, X., Duarte, M., Tang, X. Chronic exposure to air pollution particles increases the risk of obesity and metabolic syndrome: findings from a natural experiment in Beijing. PMID- 26891736 TI - Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat. AB - Vaccenic acid (VA), the predominant ruminant-derivedtransfat in the food chain, ameliorates hyperlipidemia, yet mechanisms remain elusive. We investigated whether VA could influence tissue endocannabinoids (ECs) by altering the availability of their biosynthetic precursor, arachidonic acid (AA), in membrane phospholipids (PLs). JCR:LA-cprats were assigned to a control diet with or without VA (1% w/w),cis-9,trans-11 conjugated linoleic acid (CLA) (1% w/w) or VA+CLA (1% + 0.5% w/w) for 8 weeks. VA reduced the EC, 2-arachidonoylglycerol (2 AG), in the liver and visceral adipose tissue (VAT) relative to control diet (P< 0.001), but did not change AA in tissue PLs. There was no additive effect of combining VA+CLA on 2-AG relative to VA alone (P> 0.05). Interestingly, VA increased jejunal concentrations of anandamide and those of the noncannabinoid signaling molecules, oleoylethanolamide and palmitoylethanolamide, relative to control diet (P< 0.05). This was consistent with a lower jejunal protein abundance (but not activity) of their degrading enzyme, fatty acid amide hydrolase, as well as the mRNA expression of TNFalpha and interleukin 1beta (P< 0.05). The ability of VA to reduce 2-AG in the liver and VAT provides a potential mechanistic explanation to alleviate ectopic lipid accumulation. The opposing regulation of ECs and other noncannabinoid lipid signaling molecules by VA suggests an activation of benefit via the EC system in the intestine. PMID- 26891737 TI - Detection and confirmation of serum lipid biomarkers for preeclampsia using direct infusion mass spectrometry. AB - Despite substantial research, the early diagnosis of preeclampsia remains elusive. Lipids are now recognized to be involved in regulation and pathophysiology of some disease. Shotgun lipidomic studies were undertaken to determine whether serum lipid biomarkers exist that predict preeclampsia later in the same in pregnancy. A discovery study was performed using sera collected at 12 14 weeks pregnancy from 27 controls with uncomplicated pregnancies and 29 cases that later developed preeclampsia. Lipids were extracted and analyzed by direct infusion into a TOF mass spectrometer. MS signals, demonstrating apparent differences were selected, their abundances determined, and statistical differences tested. Statistically significant lipid markers were reevaluated in a second confirmatory study having 43 controls and 37 preeclampsia cases. Multi marker combinations were developed using those lipid biomarkers confirmed in the second study. The initial study detected 45 potential preeclampsia markers. Of these, 23 markers continued to be statistically significant in the second confirmatory set. Most of these markers, representing several lipid classes, were chemically characterized, typically providing lipid class and potential molecular components using MS(2) Several multi-marker panels with areas under the curve >0.85 and high predictive values were developed. Developed panels of serum lipidomic biomarkers appear to be able to identify most women at risk for preeclampsia in a given pregnancy at 12-14 weeks gestation. PMID- 26891738 TI - HDL is redundant for adrenal steroidogenesis in LDLR knockout mice with a human like lipoprotein profile. AB - The contribution of HDL to adrenal steroidogenesis appears to be different between mice and humans. In the current study, we tested the hypothesis that a difference in lipoprotein profile may be the underlying cause. Hereto, we determined the impact of HDL deficiency on the adrenal glucocorticoid output in genetically modified mice with a human-like lipoprotein profile. Genetic deletion of APOA1 in LDL receptor (LDLR) knockout mice was associated with HDL deficiency and a parallel increase in the level of cholesterol associated with nonHDL fractions. Despite a compensatory increase in the adrenal relative mRNA expression levels of the cholesterol synthesis gene, HMG-CoA reductase, adrenals from APOA1/LDLR double knockout mice were severely depleted of neutral lipids, as compared with those of control LDLR knockout mice. However, basal corticosterone levels and the adrenal glucocorticoid response to stress were not different between the two types of mice. In conclusion, we have shown that HDL is not critical for proper adrenal glucocorticoid function when mice are provided with a human-like lipoprotein profile. Our findings provide the first experimental evidence that APOB-containing lipoproteins may facilitate adrenal steroidogenesis, in an LDLR-independent manner, in vivo in mice. PMID- 26891740 TI - Ascending Aortic Aneurysm in Angiotensin II-Infused Mice: Formation, Progression, and the Role of Focal Dissections. AB - OBJECTIVE: To understand the anatomy and physiology of ascending aortic aneurysms in angiotensin II-infused ApoE(-/-) mice. APPROACH AND RESULTS: We combined an extensive in vivo imaging protocol (high-frequency ultrasound and contrast enhanced microcomputed tomography at baseline and after 3, 10, 18, and 28 days of angiotensin II infusion) with synchrotron-based ultrahigh resolution ex vivo imaging (phase contrast X-ray tomographic microscopy) in n=47 angiotensin II infused mice and 6 controls. Aortic regurgitation increased significantly over time, as did the luminal volume of the ascending aorta. In the samples that were scanned ex vivo, we observed one or several focal dissections, with the largest located in the outer convex aspect of the ascending aorta. The volume of the dissections moderately correlated to the volume of the aneurysm as measured in vivo (r(2)=0.46). After 3 days of angiotensin II infusion, we found an interlaminar hematoma in 7/12 animals, which could be linked to an intimal tear. There was also a significant increase in single laminar ruptures, which may have facilitated a progressive enlargement of the focal dissections over time. At later time points, the hematoma was resorbed and the medial and adventitial thickness increased. Fatal transmural dissection occurred in 8/47 mice at an early stage of the disease, before adventita remodeling. CONCLUSIONS: We visualized and quantified the dissections that lead to ascending aortic aneurysms in angiotensin II-infused mice and provided unique insight into the temporal evolution of these lesions. PMID- 26891739 TI - Extracellular Matrix Disarray as a Mechanism for Greater Abdominal Versus Thoracic Aortic Stiffness With Aging in Primates. AB - OBJECTIVE: Increased vascular stiffness is central to the pathophysiology of aging, hypertension, diabetes mellitus, and atherosclerosis. However, relatively few studies have examined vascular stiffness in both the thoracic and the abdominal aorta with aging, despite major differences in anatomy, embryological origin, and relation to aortic aneurysm. APPROACH AND RESULTS: The 2 other unique features of this study were (1) to study young (9+/-1 years) and old (26+/-1 years) male monkeys and (2) to study direct and continuous measurements of aortic pressure and thoracic and abdominal aortic diameters in conscious monkeys. As expected, aortic stiffness, beta, was increased P<0.05, 2- to 3-fold, in old versus young thoracic aorta and augmented further with superimposition of acute hypertension with phenylephrine. Surprisingly, stiffness was not greater in old thoracic aorta than in young abdominal aorta. These results can be explained, in part, by the collagen/elastin ratio, but more importantly, by disarray of collagen and elastin, which correlated best with vascular stiffness. However, vascular smooth muscle cell stiffness was not different in thoracic versus abdominal aorta in either young or old monkeys. CONCLUSIONS: Thus, aortic stiffness increases with aging as expected, but the most severe increases in aortic stiffness observed in the abdominal aorta is novel, where values in young monkeys equaled, or even exceeded, values of thoracic aortic stiffness in old monkeys. These results can be explained by alterations in collagen/elastin ratio, but even more importantly by collagen and elastin disarray. PMID- 26891742 TI - Effect of a Metalloantibiotic Produced by Pseudomonas aeruginosa on Klebsiella pneumoniae Carbapenemase (KPC)-producing K. pneumoniae. AB - Multidrug-resistant organisms (MDRO) are a great problem in hospitals, where thousands of people are infected daily, with the occurrence of high mortality rates, especially in infections caused by Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-producing Kpn). The challenge is to find new compounds that can control KPC producing-Kpn infections. The aim of this study was to evaluate the antibiotic activity of the F3d fraction produced by the Pseudomonas aeruginosa LV strain against clinical isolates of KPC-producing Kpn. The results showed that the minimum inhibitory concentration of F3d (62.5 ug mL( 1)), containing an organic metallic compound, killed planktonic cells of KPC producing Kpn strains after 30 min of incubation. At the same concentration, this fraction also showed an inhibitory effect against biofilm of these bacteria after 24 h of incubation. Treatment with the F3d fraction caused pronounced morphological alterations in both planktonic and biofilm cells of the bacteria. The inhibitory effect of the F3d fraction seems to be more selective for the bacteria than the host cells, indicating its potential in the development of new drugs for the treatment of infections caused by KPC-producing Kpn and other MDRO. PMID- 26891741 TI - Loss of Thrombomodulin in Placental Dysfunction in Preeclampsia. AB - OBJECTIVE: Preeclampsia is a pregnancy-specific syndrome characterized by placental dysfunction and an angiogenic imbalance. Systemically, levels of thrombomodulin, an endothelium- and syncytiotrophoblast-bound protein that regulates coagulation, inflammation, apoptosis, and tissue remodeling, are increased. We aimed to investigate placental thrombomodulin dysregulation and consequent downstream effects in the pathogenesis of preeclampsia. APPROACH AND RESULTS: Placentas from 28 preeclampsia pregnancies, 30 uncomplicated pregnancies, and 21 pregnancies complicated by growth restriction as extra controls were included. Immunohistochemical staining of thrombomodulin, caspase 3, and fibrin was performed. Placental mRNA expression of thrombomodulin, inflammatory markers, matrix metalloproteinases 2 and 9, and soluble Flt-1 were measured with quantitative polymerase chain reaction. Thrombomodulin mRNA expression was determined in vascular endothelial growth factor-transfected trophoblast cell lines. Thrombomodulin protein and mRNA expression were decreased in preeclampsia as compared with both control groups (P=0.001). Thrombomodulin mRNA expression correlated with maternal body mass index (P<0.01) and diastolic blood pressure (P<0.05) in preeclampsia. An increase in placental apoptotic cells was associated with preeclampsia (P<0.001). Thrombomodulin expression correlated positively with matrix metalloproteinase expression (P<0.01) in preeclampsia, but not with fibrin deposits or inflammatory markers. Placental soluble Flt-1 expression correlated with decreased thrombomodulin expression. Vascular endothelial growth factor induced upregulation of thrombomodulin expression in trophoblast cells. CONCLUSIONS: Decreased thrombomodulin expression in preeclampsia may play a role in placental dysfunction in preeclampsia and is possibly caused by an angiogenic imbalance. Hypertension and obesity are associated with thrombomodulin downregulation. These results set the stage for further basic and clinical research on thrombomodulin in the pathogenesis of preeclampsia and other syndromes characterized by endothelial dysfunction. PMID- 26891743 TI - Four cases of echogenic breast lesions: a case series and review. AB - Echogenic breast lesions are generally thought to be benign. We herein report four cases of echogenic breast lesions that were seen at our centre over 38 months. One patient had a prior history of wide excision and radiotherapy for breast cancer and was imaged as part of routine cancer surveillance, while the other three were recalled for further assessment following an abnormal screening mammogram. All four patients were assessed on ultrasonography, which demonstrated an echogenic lesion in each patient. All four lesions underwent ultrasonography guided core biopsy, followed by excision biopsy. The indications for biopsy were interval increase in the size of lesion or indeterminate features demonstrated in the lesion. Three lesions were benign, while the lesion from the patient who had received previous radiotherapy was angiosarcoma. Not all echogenic lesions are benign and lesions with suspicious features on ultrasonography should undergo biopsy. PMID- 26891744 TI - Endoscopic facelift of the frontal and temporal areas in multiple planes. AB - INTRODUCTION: The detachment planes used in endoscopic facelifts play an important role in determining the results of facial rejuvenation. In this study, we introduced the use of multiple detachment planes for endoscopic facelifts of the frontal and temporal areas, and examined its outcome. METHODS: This study included 47 patients (38 female, 9 male) who requested frontal and temporal facelifts from January 2009 to January 2014. The technique of dissection in multiple planes was used for all 47 patients. In this technique, the frontal dissection was first carried out in the subgaleal plane, before being changed to the subperiosteal plane about 2 cm above the eyebrow line. Temporal dissection was carried out in both the subcutaneous and subgaleal planes. After detachment, frontal and temporal fixations were achieved using nonabsorbable sutures, and the incisions were closed. During follow-up (ranging from 6-24 months after surgery), the patients were shown their pre- and postoperative images, and asked to rate their satisfaction with the procedure. Complications encountered were documented. RESULTS: All 47 patients had complete recovery without any serious complications. The patient satisfaction rate was 93.6%. Minor complications included dimpling at the suture site, asymmetry, overcorrection, transitory paralysis, late oedema, haematoma, infection, scarring and hair loss. These complications resolved spontaneously and were negligible after complete recovery. CONCLUSION: Dissection in multiple planes is valuable in frontal and temporal endoscopic facelifts. It may be worthwhile to introduce the use of this technique in frontal and temporal facelifts, as it may lead to improved outcomes. PMID- 26891745 TI - Evaluation of a training programme to induct medical students in delivering public health talks. AB - INTRODUCTION: It is uncommon for medical students to deliver public health talks as part of their medical education curriculum. This study evaluated the effectiveness of a novel training programme that required medical students to deliver public health talks during their family medicine (FM) clerkship in a Singapore primary care institution. METHODS: The FM faculty staff guided teams of third-year medical students to select appropriate topics for health talks that were to be conducted at designated polyclinics. The talks were video-recorded and appraised for clarity, content and delivery. The appraisal was done by the student's peers and assigned faculty staff. The audience was surveyed to determine their satisfaction level and understanding of the talks. The students also self-rated the effectiveness of this new teaching activity. RESULTS: A total of 120 medical students completed a questionnaire to rate the effectiveness of the new teaching activity. 85.8% of the students felt confident about the delivery of their talks, 95.8% reported having learnt how to deliver talks and 92.5% perceived this new training modality as useful in their medical education. Based on the results of the audience survey, the speakers were perceived as knowledgeable (53.1%), confident (51.3%) and professional (39.0%). Assessment of 15 video-recorded talks showed satisfactory delivery of the talks by the students. CONCLUSION: The majority of the students reported a favourable overall learning experience under this new training programme. This finding is supported by the positive feedback garnered from the audience, peers of the medical students and the faculty staff. PMID- 26891746 TI - Changes of the corticospinal tract in the unaffected hemisphere in stroke patients: A diffusion tensor imaging study. AB - We investigated changes of the corticospinal tract (CST) in the unaffected hemisphere according to severity of the CST injury, using diffusion tensor imaging (DTI). According to the severity of the CST injury in the affected hemisphere, the stroke patients showed different aspects of fiber volume increment of the CST in the unaffected hemisphere; the fiber volume was increased in the early phase in patients with mild injury of CST and later phase in patients with severe injury of CST. PMID- 26891747 TI - The effect of anatomical noise on perception of low contrast in intra-oral radiographs: an in vitro study. AB - OBJECTIVES: Radiographic images suffer from varying amounts of noise. The most studied and discussed of these is random noise. However, recent research has shown that the projected anatomy contributes substantially to noise, especially when detecting low-contrast objects in the images. Our aim, therefore, was to evaluate the extent to which overprojected anatomical noise affects the detection of low-contrast objects in intra-oral images. METHODS: Our study used four common sensor models. With each sensor, we took four series of images, three series with and one series without an anatomical phantom present. In each series, we exposed a low-contrast phantom at 18 different exposure times using a standardized method. 4 observers evaluated all 288 images. RESULTS: The low-contrast characteristics differed substantially when imaging low contrast on a homogeneous background compared with imaging low contrast when an anatomical phantom was present. For three of the sensors, optimal exposure times for low-contrast imaging were found, while the fourth sensor displayed a completely different behaviour. CONCLUSIONS: Calibrating the low-contrast properties of an imaging system using low-contrast objects on a homogeneous background is not recommended. On an anatomical background, low-contrast properties are completely different, and these will mimic the clinical situation much more closely, directing the operator how to best use the system. There is a clear demand for further research on this subject. PMID- 26891748 TI - Calcium phosphate nanocoatings and nanocomposites, part 2: thin films for slow drug delivery and osteomyelitis. AB - During the last two decades although many calcium phosphate based nanomaterials have been proposed for both drug delivery, and bone regeneration, their coating applications have been somehow slow due to the problems related to their complicated synthesis methods. In order to control the efficiency of local drug delivery of a biomaterial the critical pore sizes as well as good control of the chemical composition is pertinent. A variety of calcium phosphate based nanocoated composite drug delivery systems are currently being investigated. This review aims to give an update into the advancements of calcium phosphate nanocoatings and thin film nanolaminates. In particular recent research on PLA/hydroxyapatite composite thin films and coatings into the slow drug delivery for the possible treatment of osteomyelitis is covered. PMID- 26891749 TI - Fibulin-5 downregulates Ki-67 and inhibits proliferation and invasion of breast cancer cells. AB - Fibulins not only function as molecular bridges within the cellular microenvironment but also influence cell behavior. Thus, fibulins may contribute to create a permissive microenvironment for tumor growth but can also stimulate different mechanisms that may impede tumor progression. This is the case with Fibulin-5, which has been shown to display both tumor-promoting and tumor protective functions by mechanisms that are not totally defined. We show new evidence on the tumor-protective functions displayed by Fibulin-5 in MCF-7, T47D and MDA-MB-231 breast cancer cells including the inhibition of invasion and proliferation capacity and hampering the ability to form mammospheres. Reduction in the level of phosphorylation of Ser residues involved in the nuclear translocation of beta-catenin may underlie these antitumor effects. We also found that Fibulin-5 reduces the level of expression of Ki-67, a nuclear protein associated with cell proliferation. Moreover, reduction in Fibulin-5 expression corresponds to an increase of Ki-67 detection in breast tissue samples. Overall, our data provide new insights into the influence of Fibulin-5 to modify breast cancer cell behavior and contribute to better understand the connections between fibulins and cancer. PMID- 26891750 TI - Dual-energy computed tomography has limited sensitivity for non-tophaceous gout: a comparison study with tophaceous gout. AB - BACKGROUND: Dual-energy computed tomography (DECT) is a new diagnostic tool for gout, but its sensitivity has not been established. Our goal was to assess the sensitivity of DECT for the detection of monosodium urate (MSU) deposits in non tophaceous and tophaceous gout, both at the level of the patient and that of the individual joint or lesion. METHODS: DECT was performed on 11 patients with crystal-proven non-tophaceous gout and 10 with tophaceous gout and included both the upper and lower extremities in 20/21 patients. DECT images were simultaneously acquired at 80 and 140 kV and then processed on a workstation with proprietary software using a two-material decomposition algorithm. MSU deposits were color coded as green by the software and fused onto grey-scale CT images. The number and location of these deposits was tallied independently by two DECT trained radiologists blinded to the clinical characteristics of the patient. Sensitivity of DECT was defined as the proportion of patients with a confirmed diagnosis of gout which was correctly identified as such by the imaging technique. All patients provided informed consent to participate in this IRB approved study. RESULTS: MSU deposits were detected by DECT in >=1 joint area in 7/11 (64 %) patients with non-tophaceous gout, but were only detected in 3/12 (25 %) joints proven by aspiration to be affected with gout. Inclusion of the upper extremity joints in the scanning protocol did not improve sensitivity. All 10 patients with tophaceous gout had MSU deposits evident by DECT. The sensitivity of DECT for individual gouty erosions was assessed in 3 patients with extensive foot involvement. MSU deposits were detected by DECT within or immediately adjacent to 13/26 (50 %) erosions. CONCLUSIONS: A DECT protocol that includes all lower extremity joints has moderate sensitivity in non-tophaceous and high sensitivity in tophaceous gout. However, DECT has lower sensitivity when restricted to individual crystal-proven gouty joints in non-tophaceous disease or individual erosive lesions in tophaceous gout. The detection of MSU deposits by DECT relates to their size and density and the detection parameters of the DECT scanner and adjustment of the latter might improve sensitivity. PMID- 26891751 TI - Kinematic and kinetic assessment of upper limb movements in patients with writer's cramp. AB - BACKGROUND: The assessment and treatment of writer's cramp is complicated due to the variations in the forces and angles of involved joints. Additionally, in some cases compensatory movements for cramp relief further complicates assessment. Currently these variables are subjectively measured with clinical scales and visual assessments. This subjectivity makes it difficult to successfully administer interventions such as Botulinum toxin injection or orthotics resulting in poor efficacy and significant side effects. METHOD: A multi-sensor system was used to record finger and wrist forces along with deviation angles at the wrist, elbow and shoulder while 9 patients with writer's cramp performed a series of standardized tasks on surfaces inclined at different angles. Clinical, kinetic, and kinematic information regarding cramping was collected. RESULTS: First, four tasks appeared to best predict cramp occurrence. Second, unique biomechanical profiles emerged for patients regarding force, angles and cramp severity. Third, cluster analyses using these features showed a clear separation of patients into two severity classes. Finally, a relationship between severity and kinetic kinematic information suggested that primary cramping versus compensatory movements could be potentially inferred. CONCLUSIONS: The results demonstrate that using a set of standardized tasks and objective measures, individual profiles for arm movements and applied forces associated with writer's cramp can be generated. The clinician can then accurately target the biomechanics specifically, whether it is with injection or other rehabilitative measures, fulfilling an important unmet need in the treatment of writer's cramp. PMID- 26891752 TI - Implementation of CE-MS-identified proteome-based biomarker panels in drug development and patient management. AB - The recent advancements in clinical proteomics enabled identification of biomarker panels for a large range of diseases. A number of CE-MS-identified biomarker panels were verified and implemented in clinical studies. Despite multiple challenges, accumulating evidence supports the value and the need for proteome-based biomarker panels. In this perspective, we provide an overview of clinical studies indicating the added value of CE-MS biomarker panels over traditional diagnostics and monitoring methods. We outline apparent advantages of applying novel proteomic biomarker panels for disease diagnosis, prognosis, staging, drug development and patient management. Facing the plethora of benefits associated with the use of CE-MS biomarker panels, we envision their implementation into the medical practice in the near future. PMID- 26891753 TI - The combined effect of subcutaneous granulocyte- colony stimulating factor and myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride on post-infarction left ventricular function, the RIGENERA 2.0 trial: study protocol for a randomized controlled trial. AB - BACKGROUND: Several clinical trials and recent meta-analyses have demonstrated that administration of recombinant human granulocyte-colony stimulating factor (G CSF) is safe and, only in patients with large acute myocardial infarction (AMI), is associated with an improvement in left ventricular ejection fraction. Moreover, the mobilization and engraftment of the bone marrow-derived cells may differ significantly among patients, interfering with the restoration of left ventricular function after treatment. Therefore, the clinical potential application of the G-CSF has not yet been fully elucidated. METHODS/DESIGN: The RIGENERA 2.0 trial is a multicenter, phase II, placebo-controlled, randomized, open-label, with blinded evaluation of endpoints (PROBE) trial in which 120 patients with an acute ST-elevation myocardial infarction (STEMI) undergoing successful revascularization but with residual myocardial dysfunction will be enrolled. In cases where there is a left ventricular ejection fraction (LVEF) <= 45% the patient will be electronically randomized (1:1 ratio) to receive either subcutaneous recombinant human G-CSF (group 1) or placebo (group 2) both added on top of optimal standard of care. Both groups will undergo myocardial contrast echocardiography with intravenous infusion of sulfur hexafluoride (MCE) whilst undergoing the echocardiogram. The primary efficacy endpoint is the evaluation of the LVEF at 6 months after AMI assessed by cardiac magnetic resonance. Secondary efficacy endpoints are the evaluation of LVEF at 6 months after AMI assessed by echocardiography, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) assessed by cardiac magnetic resonance and echocardiography at 6 months, together with the incidence of major adverse clinical events (MACE) defined as death, myocardial infarction, sustained cardiac arrhythmias, cardiogenic shock, stroke and re-hospitalization due to heart failure at 1 year. DISCUSSION: The RIGENERA 2.0 trial will test whether G-CSF administration and MCE, through the enhancement of the bone marrow-derived cells homing in the myocardium, determines an improvement in regional and global contractile function, myocardial perfusion and infarct extension in patients with large AMI. The results of the present study are expected to envision routine clinical use of this safe, affordable and reproducible approach in patients with successful revascularization after AMI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02502747 (29 June 2015); EudraCT: 2015-002189-21 (10 July 2015). PMID- 26891755 TI - Back to the future: re-evaluation of the possible role for oxygen supplementation during exercise in chronic heart failure. PMID- 26891754 TI - The effect of increasing inspired oxygen on exercise performance in patients with chronic heart failure. AB - OBJECTIVE: Chronic heart failure is characterised by reduced exercise tolerance. We assessed the effects of different fractions of inspired oxygen (FiO2) on exercise capacity using cycle ergometry to see if there is a dose-response relationship between FiO2 and exercise performance. METHODS: This was a single centre, randomised, single-blinded, cross-over study. Thirty-one patients with chronic heart failure undertook three maximal incremental exercise tests. For each test, a different FiO2 was used: room air (20.9%), 28% or 40%. The patient had to breathe in via a venturi mask allowing the investigator to control the FiO2 and maintain the patient's blinding. The three tests were carried out in random order with a minimum of 4 days' rest between any two tests. RESULTS: Exercise time increased from (mean+/-standard deviations) 501+/-24.9 s on room air to 525+/-25.1 s (p=0.042) and 536+/-24.2 (p<0.001) seconds, with FiO2 of 28% and 40%, respectively. Maximal metabolic equivalents were 3.47+/-0.16 on room air and 3.67+/-0.16 (p=0.002) and 3.70+/-0.15 (p<0.001) on 28% and 40% oxygen, respectively. Maximal workload was 78.4+/-4.5 W on room air and 82.6+/-4.3 (p=0.021) and 84.2+/-4.2 (p=0.005) on 28% and 40% oxygen, respectively. Increasing FiO2 resulted in higher mean oxygen saturations during exercise. The mean heart rate during exercise was lower with FiO2 of 28% with no further drop at 40%. Changing FiO2 had no effect on blood pressure. CONCLUSIONS: Increasing FiO2 to 28% or 40% acutely improves exercise capacity in patients with chronic heart failure. TRIAL REGISTRATION NUMBER: Eudract number: 2014-003380-38; Results. PMID- 26891756 TI - Ticagrelor and aspirin for the prevention of cardiovascular events after coronary artery bypass graft surgery. AB - BACKGROUND: Ticagrelor was shown to reduce mortality in patients who underwent coronary artery bypass grafting (CABG), but its effect on graft patency is unknown. METHODS: We performed a prospective, randomised, double-blind, placebo controlled trial, comparing ticagrelor 90 mg twice daily versus placebo for 3 months added to aspirin 81 mg/day, following isolated CABG. Aspirin was started within 12 h, and study medication within 72 h after CABG. Primary outcome was graft occlusion on CT angiography (CTA) performed 3 months post CABG. Patients were followed to 12 months for death, myocardial infarction, stroke, repeat revascularisation and bleeding. RESULTS: The study was terminated prematurely after randomising 70 patients between September 2011 and August 2014 because of slow recruitment. CTA was performed in 56 patients who completed >1 month of study drug. Graft occlusion occurred in 7/25 (28.0%) patients on ticagrelor and 17/31 (48.3%) on placebo, p=0.044. Of 207 analysable grafts, graft occlusion occurred in 9/87 (10.3%) with ticagrelor and 22/120 (18.3%) with placebo, p=0.112. Graft occlusion or stenosis >=50% occurred in 10/87 (11.5%) ticagrelor vs 32/120 (26.7%) placebo, p=0.007. There was no major bleeding, but minor bleeding was higher with ticagrelor (31.4% vs 2.9%, p=0.003). In univariate analysis, ticagrelor use reduced graft occlusion (OR 0.32, 95% CI 0.10 to 0.97, p=0.047), which remained significant on multivariable analysis (OR 0.25, 95% CI 0.073 to 0.873, p=0.03). CONCLUSIONS: Ticagrelor added to aspirin after CABG reduced the proportion of patients with graft occlusion, and was a significant univariate and multivariable predictor of graft occlusion. These results are hypothesis-generating and should be confirmed in larger studies. TRIAL REGISTRATION NUMBER: NCT01373411: Results. PMID- 26891757 TI - Rheumatic heart disease echocardiographic screening: approaching practical and affordable solutions. AB - Rheumatic heart disease (RHD) affects at least 32.9 million people worldwide and ranks as a leading cause of death and disability in low-income and middle-income countries (LMICs). Echocardiographic screening has been demonstrated to be a powerful tool for early RHD detection, and holds potential for global RHD control. However, national screening programmes have not emerged. Major barriers to implementation include the lack of human and financial resources in LMICs. Here, we focus on recent research advances that could make echocardiographic screening more practical and affordable, including handheld echocardiography devices, simplified screening protocols and task shifting of echocardiographic screening to non-experts. Additionally, we highlight some important remaining questions before echocardiographic screening can be widely recommended, including demonstration of cost-effectiveness, assessment of the impact of screening on children and communities, and determining the importance of latent RHD. While a single strategy for echocardiographic screening in all high-prevalence areas is unlikely, we believe recent advancements are bringing the public health community closer to developing sustainable programmes for echocardiographic screening. PMID- 26891760 TI - Autofluorescence-delineated macular hole size predicts postoperative visual outcome. PMID- 26891758 TI - Effectiveness of insecticidal nets on uncomplicated clinical malaria: a case control study for operational evaluation. AB - BACKGROUND: In a context of large-scale implementation of malaria vector control tools, such as the distribution of long-lasting insecticide nets (LLIN), it is necessary to regularly assess whether strategies are progressing as expected and then evaluate their effectiveness. The present study used the case-control approach to evaluate the effectiveness of LLIN 42 months after national wide distribution. This study design offers an alternative to cohort study and randomized control trial as it permits to avoid many ethical issues inherent to them. METHODS: From April to August 2011, a case-control study was conducted in two health districts in Benin; Ouidah-Kpomasse-Tori (OKT) in the south and Djougou-Copargo-Ouake (DCO) in the north. Children aged 0-60 months randomly selected from community were included. Cases were children with a high axillary temperature (>=37.5 degrees C) or a reported history of fever during the last 48 h with a positive rapid diagnostic test (RDT). Controls were children with neither fever nor signs suggesting malaria with a negative RDT. The necessary sample size was at least 396 cases and 1188 controls from each site. The main exposure variable was "sleeping every night under an LLIN for the 2 weeks before the survey" (SL). The protective effectiveness (PE) of LLIN was calculated as PE = 1 - odds ratio. RESULTS: The declared SL range was low, with 17.0 and 27.5 % in cases and controls in the OKT area, and 44.9 and 56.5 % in cases and controls, in the DCO area, respectively. The declared SL conferred 40.5 % (95 % CI 22.2-54.5 %) and 55.5 % (95 % CI 28.2-72.4 %) protection against uncomplicated malaria in the OKT and the DCO areas, respectively. Significant differences in PE were observed according to the mother's education level. CONCLUSION: In the context of a mass distribution of LLIN, their use still conferred protection in up to 55 % against the occurrence of clinical malaria cases in children. Social factors, the poor use and the poor condition of an LLIN can be in disfavour with its effectiveness. In areas, where LLIN coverage is assumed to be universal or targeted at high-risk populations, case-control studies should be regularly conducted to monitor the effectiveness of LLIN. The findings will help National Malaria Control Programme and their partners to improve the quality of malaria control according to the particularity of each area or region as far as possible. PMID- 26891759 TI - EMOTIONAL AVAILABILITY IN EARLY MOTHER-CHILD INTERACTIONS FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS, OTHER PSYCHIATRIC DISORDERS, AND DEVELOPMENTAL DELAY. AB - Emotional availability (EA) is a method to assess early parent-child dyadic interactions for emotional awareness, perception, experience, and expression between child and parent that describe global relational quality (Z. Biringen & M. Easterbrooks, 2012). The current study aimed to examine the effects of an infant's diagnosis of autism spectrum disorders (ASDs), other psychiatric disorders (OPD), and developmental delay (DD) on the maternal EA Scale (EAS; Z. Biringen & M. Easterbrooks, 2012; Z. Biringen, J.L. Robinson, & R.N. Emde, 2000) scores and the relative contributions of infant's age, gender, diagnosis, developmental level, and maternal education on EAS scores in a clinical Turkish sample. Three hundred forty-five infant-mother dyads participated in this study. Results of the research indicated that EAS adult scores were associated with maternal education and infant's diagnosis whereas child scores were associated with infant's age, diagnosis, and developmental level. Infants' involvement and responsiveness to the mother were lower in the group with ASD. Children with OPD, particularly when their mothers have lower education, might be at increased risk of having problems in parent-child interactions. Young ASD subjects with developmental delay are in greatest need of support to increase reactions toward their mother. These findings underscore the importance of using all of the EA dimensions rather than only one measure on children in high-risk populations. PMID- 26891763 TI - Air humidity as key determinant of morphogenesis and productivity of the rare temperate woodland fern Polystichum braunii. AB - (1) Most ferns are restricted to moist and shady habitats, but it is not known whether soil moisture or atmospheric water status are decisive limiting factors, or if both are equally important. (2) Using the rare temperate woodland fern Polystichum braunii, we conducted a three-factorial climate chamber experiment (soil moisture (SM) * air humidity (RH) * air temperature (T)) to test the hypotheses that: (i) atmospheric water status (RH) exerts a similarly large influence on the fern's biology as soil moisture, and (ii) both a reduction in RH and an increase in air temperature reduce vigour and growth. (3) Nine of 11 morphological, physiological and growth-related traits were significantly influenced by an increase in RH from 65% to 95%, leading to higher leaf conductance, increased above- and belowground productivity, higher fertility, more epidermal trichomes and fewer leaf deformities under high air humidity. In contrast, soil moisture variation (from 66% to 70% in the moist to ca. 42% in the dry treatment) influenced only one trait (specific leaf area), and temperature variation (15 degrees C versus 19 degrees C during daytime) only three traits (leaf conductance, root/shoot ratio, specific leaf area); RH was the only factor affecting productivity. (4) This study is the first experimental proof for a soil moisture-independent air humidity effect on the growth of terrestrial woodland ferns. P. braunii appears to be an air humidity hygrophyte that, whithin the range of realistic environmental conditions set in this study, suffers more from a reduction in RH than in soil moisture. A climate warming-related increase in summer temperatures, however, seems not to directly threaten this endangered species. PMID- 26891764 TI - Comparative embryogenesis of Mecoptera and Lepidoptera with special reference to the abdominal prolegs. AB - The eruciform larvae of holometabolous insects are primarily characterized by bearing a varying number of abdominal prolegs in addition to three pairs of thoracic legs. However, whether the prolegs are evolutionarily homologous among different insect orders is still a disputable issue. We examined the embryonic features and histological structure of the prolegs of the scorpionfly Panorpa byersi Hua and Huang (Mecoptera: Panorpidae) and the Oriental armyworm Mythimna separata (Walker) (Lepidoptera: Noctuidae) to investigate whether the prolegs are homologous between these two holometabolous insect orders. In the scorpionfly, paired lateral process primordia arise on abdominal segments I-VIII (A1-A8) in line with the thoracic legs in early embryonic stages, but degenerate into triangular protuberances in later stages, and paired medial processes appear along the midventral line before dorsal closure and eventually develop into unjointed, cone-shaped prolegs. Histological observation showed that the lumina of the prolegs are not continuous with the hemocoel, differing distinctly from that of the basic appendicular plan of thoracic legs. These results suggest that the prolegs are likely secondary outgrowths in Mecoptera. In the armyworm, lateral process primordia appear on A1-A10 in alignment with the thoracic legs in the early embryonic stages, although only the rudiments on A3-A6 and A10 develop into segmented prolegs with the lumina continuous with the hemocoel and others degenerate eventually, suggesting that the prolegs are true segmental appendages serially homologous with the thoracic legs in Lepidoptera. Therefore, we conclude that the larval prolegs are likely not evolutionarily homologous between Mecoptera and Lepidoptera. PMID- 26891761 TI - Graphene Facilitated Removal of Labetalol in Laccase-ABTS System: Reaction Efficiency, Pathways and Mechanism. AB - The widespread occurrence of the beta-blocker labetalol causes environmental health concern. Enzymatic reactions are highly efficient and specific offering biochemical transformation of trace contaminants with short reaction time and little to none energy consumption. Our experiments indicate that labetalol can be effectively transformed by laccase-catalyzed reaction using 2, 2-Azino-bis-(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a mediator, while no significant removal of labetalol can be achieved in the absence of ABTS. A total of three products were identified. It is interesting that the presence of graphene greatly increased the reaction rate while not changed the products. In the presence of 100 MUg/L graphene, the pseudo-first-order reaction rate constant was increased ~50 times. We found that the enhancement of graphene is probably attributed to the formation and releasing of ABTS(2+) which has a much greater reactivity towards labetalol when graphene is present. This study provides fundamental information for laccase-ABTS mediated labetalol reactions and the effect of graphene, which could eventually lead to development of novel methods to control beta-blocker contamination. PMID- 26891762 TI - Combined strategies for optimal detection of the contact point in AFM force indentation curves obtained on thin samples and adherent cells. AB - Atomic Force Microscopy (AFM) is a widely used tool to study cell mechanics. Current AFM setups perform high-throughput probing of living cells, generating large amounts of force-indentations curves that are subsequently analysed using a contact-mechanics model. Here we present several algorithms to detect the contact point in force-indentation curves, a crucial step to achieve fully-automated analysis of AFM-generated data. We quantify and rank the performance of our algorithms by analysing a thousand force-indentation curves obtained on thin soft homogeneous hydrogels, which mimic the stiffness and topographical profile of adherent cells. We take advantage of the fact that all the proposed algorithms are based on sequential search strategies, and show that a combination of them yields the most accurate and unbiased results. Finally, we also observe improved performance when force-indentation curves obtained on adherent cells are analysed using our combined strategy, as compared to the classical algorithm used in the majority of previous cell mechanics studies. PMID- 26891765 TI - A competitive and reversible deactivation approach to catalysis-based quantitative assays. AB - Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation. PMID- 26891766 TI - Revisiting the link between hypertension and hemifacial spasm. AB - The relationship between hypertension and hemifacial spasm (HFS) has been debated. Microvascular decompression surgery is effective in some HFS patients with uncontrolled hypertension. To address current gaps in knowledge, we conducted a meta-analysis of case-control studies that have examined the prevalence of hypertension in HFS patients compared to non-HFS controls. We also evaluated the implications and limitations of the pooled studies. We identified 62 studies from PubMed, The Cochrane Library, Web of Science and Scholar.google.com and six studies that fit our inclusion criteria were included. A random-effects model was used to derive the pooled estimate of the Odds Ratio. The data was plotted on a Forest plot. A pooled analysis involving 51585 subjects, 549 cases, 720 neurological controls and 50316 controls from the general population, showed that HFS patients had a higher chance of developing hypertension (OR = 1.72, 95% CI = (1.12, 2.31), p-value <0.001). The prevalence of hypertension was higher in HFS patients as compared to non-HFS patients. This meta-analysis highlights a positive correlation between hypertension and HFS. Blood pressure should be closely monitored during the follow-up of HFS patients. Preliminary links between ventrolateral medullary (VLM) compression and HFS should be further evaluated in future studies. PMID- 26891767 TI - Parkinsonism, movement disorders and genetics in frontotemporal dementia. AB - Frontotemporal dementia (FTD) refers to a group of clinically and genetically heterogeneous neurodegenerative disorders that are a common cause of adult-onset behavioural and cognitive impairment. FTD often presents in combination with various hyperkinetic or hypokinetic movement disorders, and evidence suggests that various genetic mutations underlie these different presentations. Here, we review the known syndromatic-genetic correlations in FTD. Although no direct genotype-phenotype correlations have been identified, mutations in multiple genes have been associated with various presentations. Mutations in the genes that encode microtubule-associated protein tau (MAPT) and progranulin (PGRN) can manifest as symmetrical parkinsonism, including the phenotypes of Richardson syndrome and corticobasal syndrome (CBS). Expansions in the C9orf72 gene are most frequently associated with familial FTD, typically combined with motor neuron disease, but other manifestations, such as symmetrical parkinsonism, CBS and multiple system atrophy-like presentations, have been described in patients with these mutations. Less common gene mutations, such as those in TARDBP, CHMP2B, VCP, FUS and TREM2, can also present as atypical parkinsonism. The most common hyperkinetic movement disorders in FTD are motor and vocal stereotypies, which have been observed in up to 78% of patients with autopsy-proven FTD. Other hyperkinetic movements, such as chorea, orofacial dyskinesias, myoclonus and dystonia, are also observed in some patients with FTD. PMID- 26891770 TI - Stroke: MCEMP1--a new prognostic and diagnostic biomarker for stroke? PMID- 26891771 TI - Generalized granuloma annulare successfully treated with narrowband ultraviolet B and anti-hepatitis C virus therapy. PMID- 26891768 TI - Ultrasound treatment of neurological diseases--current and emerging applications. AB - Like cardiovascular disease and cancer, neurological disorders present an increasing challenge for an ageing population. Whereas nonpharmacological procedures are routine for eliminating cancer tissue or opening a blocked artery, the focus in neurological disease remains on pharmacological interventions. Setbacks in clinical trials and the obstacle of access to the brain for drug delivery and surgery have highlighted the potential for therapeutic use of ultrasound in neurological diseases, and the technology has proved useful for inducing focused lesions, clearing protein aggregates, facilitating drug uptake, and modulating neuronal function. In this Review, we discuss milestones in the development of therapeutic ultrasound, from the first steps in the 1950s to recent improvements in technology. We provide an overview of the principles of diagnostic and therapeutic ultrasound, for surgery and transient opening of the blood-brain barrier, and its application in clinical trials of stroke, Parkinson disease and chronic pain. We discuss the promising outcomes of safety and feasibility studies in preclinical models, including rodents, pigs and macaques, and efficacy studies in models of Alzheimer disease. We also consider the challenges faced on the road to clinical translation. PMID- 26891772 TI - Optimized and validated high-performance liquid chromatography method for the determination of deoxynivalenol and aflatoxins in cereals. AB - A simple, sensitive and accurate analytical method was optimized and developed for the determination of deoxynivalenol and aflatoxins in cereals intended for human consumption using high-performance liquid chromatography with diode array and fluorescence detection and a photochemical reactor for enhanced detection. A response surface methodology, using a fractional central composite design, was carried out for optimization of the water percentage at the beginning of the run (X1, 80-90%), the level of acetonitrile at the end of gradient system (X2, 10 20%) with the water percentage fixed at 60%, and the flow rate (X3, 0.8-1.2 mL/min). The studied responses were the chromatographic peak area, the resolution factor and the time of analysis. Optimal chromatographic conditions were: X1 = 80%, X2 = 10%, and X3 = 1 mL/min. Following a double sample extraction with water and a mixture of methanol/water, mycotoxins were rapidly purified by an optimized solid-phase extraction protocol. The optimized method was further validated with respect to linearity (R(2) >0.9991), sensitivity, precision, and recovery (90 112%). The application to 23 commercial cereal samples from Greece showed contamination levels below the legally set limits, except for one maize sample. The main advantages of the developed method are the simplicity of operation and the low cost. PMID- 26891769 TI - Auditory neuropathy--neural and synaptic mechanisms. AB - Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they "can hear but cannot understand". This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function--resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca(2+) influx, or synaptic vesicle exocytosis--leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies. PMID- 26891773 TI - Combining the absorptive and radiative loss in metasurfaces for multi-spectral shaping of the electromagnetic scattering. AB - The absorptive and radiative losses are two fundamental aspects of the electromagnetic responses, which are widely occurring in many different systems such as waveguides, solar cells, and antennas. Here we proposed a metasurface to realize the control of the absorptive and radiative loss and to reduce the radar cross section (RCS) in multi-frequency bands. The anti-phase gradient and absorptive metasurfaces were designed that consists of metallic square patch and square loop structure inserted with resistors, acting as an phase gradient material in the X and Ku band, while behaving as an absorber in the S band. The simulation and experiment results verified the double-band, wideband and polarization-independent RCS reduction by the absorptive and anti-phase gradient metasurfaces. PMID- 26891774 TI - Factors influencing health-related quality of life among Korean cancer survivors. AB - OBJECTIVE: Early cancer detection and remarkable improvements in cancer treatment have seen the cancer survival rate grow steadily for the past 40 years. Despite expectations regarding treatment effectiveness, acceptable quality of life, and a comfortable death, patients with cancer generally have a decreased quality of life. The study aim was to examine the factors influencing health-related quality of life among South Korean cancer survivors for future development of an intervention to enhance their survivorship. METHODS: Korea National Health and Nutrition Examination Survey 2008-2012 data regarding 1020 cancer survivors were used for analysis. Health-related quality of life was measured using the EuroQol 5-Dimension. RESULTS: The factors influencing health-related quality of life were age, educational status, employment status, income, smoking, time since diagnosis, subjective health status, stress, depression, and suicidal ideation. CONCLUSIONS: Individual-centered clinical interventions that consider dimensional influencing factors, including subjective health status, are needed to improve cancer survivors' health-related quality of life. Subsequent systematic studies are needed regarding dimension-specific differences according to cancer types and time since diagnosis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891775 TI - Non-stop lab week: A real laboratory experience for life sciences postgraduate courses. AB - At the Portuguese universities, practical classes of life sciences are usually professor-centered 2-hour classes. This approach results in students underprepared for a real work environment in a research/clinical laboratory. To provide students with a real-life laboratory environment, the Non-Stop Lab Week (NSLW) was created in the Molecular Biomedicine master program at the University of Aveiro, Portugal. The unique feature of the NSLW is its intensity: during a 1 week period, students perform a subcloning and a protein expression project in an environment that mimics a real laboratory. Students work autonomously, and the progression of work depends on achieving the daily goals. Throughout the three curricular years, most students considered the intensity of the NSLW a very good experience and fundamental for their future. Moreover, after some experience in a real laboratory, students state that both the techniques and the environment created in the NSLW were similar to what they experience in their current work situation. The NSLW fulfills a gap in postgraduate students' learning, particularly in practical skills and scientific thinking. Furthermore, the NSLW experience provides skills to the students that are crucial to their future research area. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44:297-303, 2016. PMID- 26891776 TI - Spatially resolved TiOx phases in switched RRAM devices using soft X-ray spectromicroscopy. AB - Reduction in metal-oxide thin films has been suggested as the key mechanism responsible for forming conductive phases within solid-state memory devices, enabling their resistive switching capacity. The quantitative spatial identification of such conductive regions is a daunting task, particularly for metal-oxides capable of exhibiting multiple phases as in the case of TiOx. Here, we spatially resolve and chemically characterize distinct TiOx phases in localized regions of a TiOx-based memristive device by combining full-field transmission X-ray microscopy with soft X-ray spectroscopic analysis that is performed on lamella samples. We particularly show that electrically pre-switched devices in low-resistive states comprise reduced disordered phases with O/Ti ratios around 1.37 that aggregate in a ~100 nm highly localized region electrically conducting the top and bottom electrodes of the devices. We have also identified crystalline rutile and orthorhombic-like TiO2 phases in the region adjacent to the main reduced area, suggesting that the temperature increases locally up to 1000 K, validating the role of Joule heating in resistive switching. Contrary to previous studies, our approach enables to simultaneously investigate morphological and chemical changes in a quantitative manner without incurring difficulties imposed by interpretation of electron diffraction patterns acquired via conventional electron microscopy techniques. PMID- 26891779 TI - Pd-Catalyzed regioselective hydroesterification of 2-allylphenols to seven membered lactones without external CO gas. AB - Effective Pd-catalyzed regioselective hydroesterification of 2-allylphenols with phenyl formate is described. A variety of seven-membered lactones can be obtained in good yields under mild conditions without the use of toxic CO gas. PMID- 26891781 TI - Solvent-dependent on/off valving using selectively permeable barriers in paper microfluidics. AB - We report on a new way to control solvent flows in paper microfluidic devices, based on the local patterning of paper with alkyl ketene dimer (AKD) to form barriers with selective permeability for different solvents. Production of the devices is a two-step process. In the first step, AKD-treated paper (hydrophobic) is exposed to oxygen plasma for re-hydrophilization. 3D-printed masks are employed to shield certain areas of this paper to preserve well-defined hydrophobic patterns. In the second step, concentrated AKD in hexane is selectively deposited onto already hydrophobic regions of the paper to locally increase the degree of hydrophobicity. Hydrophilic areas formed in the previous oxygen plasma step are protected from AKD by wetting them with water first to prevent the AKD hexane solution from entering them (hydrophilic exclusion). Characterization of the patterns after both steps shows that reproducible patterns are obtained with linear dependence on the dimensions of the 3D-printed masks. This two-step methodology leads to differential hydrophobicity on the paper: (i) hydrophilic regions, (ii) low-load AKD gates, and (iii) high-load AKD walls. The gates are impermeable to water, yet can be penetrated by most alcohol/water mixtures; the walls cannot. This concept for solvent-dependent on/off valving is demonstrated in two applications. In the first example, a device was developed for multi-step chemical reactions. Different compounds can be spotted separately (closed gates). Upon elution with an alcohol/water mixture, the gates become permeable and the contents are combined. In the second example, volume-defined sampling is introduced. Aqueous sample is allowed to wick into a device and fill a sample chamber. The contents of this sample chamber are eluted perpendicularly with an alcohol/water mixture through a selectively permeable gate. This system was tested with dye solution, and a linear dependence of magnitude of the signal on the sample chamber size was obtained. PMID- 26891778 TI - Construction of pH-responsive and up-conversion luminescent NaYF4:Yb3+/Er3+@SiO2@PMAA nanocomposite for colon targeted drug delivery. AB - Colon-targeted drug delivery system has attracted much interest because it can improve therapeutic efficacy and reduce the side effect in practical clinic. Herein, we constructed a multifunctional drug delivery system with colonic targeting and tracking by up-conversion (UC) luminescence based on core-shell structured NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite. The resultant materials exhibited bright UC luminescence, pH-responsive property and excellent biocompatibility. The drug release behaviors in different pH environment were investigated using 5-aminosalicylic acid (5-ASA) as a model drug. The 5-ASA molecules release from NaYF4:Yb(3+)/Er(3+)@SiO2@PMAA nanocomposite exhibit a significant pH-responsive colon targeted property, i.e., a little amount of drug release in simulated gastric fluid (SGF, pH = 1.2) but a large amount of drug release in simulated colonic fluid (SCF, pH = 7.4) Moreover, the drug release process could be monitored by the change of UC emission intensity. These results implied that the multifunctional nanocomposite is a promising drug carrier for targeted release of 5-ASA in the colon. PMID- 26891782 TI - No implementation without evaluation: the case of mesh in vaginal prolapse surgery. PMID- 26891780 TI - Treatment Effect Estimation Using Nonlinear Two-Stage Instrumental Variable Estimators: Another Cautionary Note. AB - OBJECTIVE: To examine the settings of simulation evidence supporting use of nonlinear two-stage residual inclusion (2SRI) instrumental variable (IV) methods for estimating average treatment effects (ATE) using observational data and investigate potential bias of 2SRI across alternative scenarios of essential heterogeneity and uniqueness of marginal patients. STUDY DESIGN: Potential bias of linear and nonlinear IV methods for ATE and local average treatment effects (LATE) is assessed using simulation models with a binary outcome and binary endogenous treatment across settings varying by the relationship between treatment effectiveness and treatment choice. PRINCIPAL FINDINGS: Results show that nonlinear 2SRI models produce estimates of ATE and LATE that are substantially biased when the relationships between treatment and outcome for marginal patients are unique from relationships for the full population. Bias of linear IV estimates for LATE was low across all scenarios. CONCLUSIONS: Researchers are increasingly opting for nonlinear 2SRI to estimate treatment effects in models with binary and otherwise inherently nonlinear dependent variables, believing that it produces generally unbiased and consistent estimates. This research shows that positive properties of nonlinear 2SRI rely on assumptions about the relationships between treatment effect heterogeneity and choice. PMID- 26891783 TI - Dissection of expression-quantitative trait locus and allele specificity using a haploid/diploid plant system - insights into compensatory evolution of transcriptional regulation within populations. AB - Regulation of gene expression plays a central role in translating genotypic variation into phenotypic variation. Dissection of the genetic basis of expression variation is key to understanding how expression regulation evolves. Such analyses remain challenging in contexts where organisms are outbreeding, highly heterozygous and long-lived such as in the case of conifer trees. We developed an RNA sequencing (RNA-seq)-based approach for both expression quantitative trait locus (eQTL) mapping and the detection of cis-acting (allele specific) vs trans-acting (non-allele-specific) eQTLs. This method can be potentially applied to many conifers. We used haploid and diploid meiotic seed tissues of a single self-fertilized white spruce (Picea glauca) individual to dissect eQTLs according to linkage and allele specificity. The genetic architecture of local eQTLs linked to the expressed genes was particularly complex, consisting of cis-acting, trans-acting and, surprisingly, compensatory cis-trans effects. These compensatory effects influence expression in opposite directions and are neutral when combined in homozygotes. Nearly half of local eQTLs were under compensation, indicating that close linkage between compensatory cis-trans factors is common in spruce. Compensated genes were overrepresented in developmental and cell organization functions. Our haploid-diploid eQTL analysis in spruce revealed that compensatory cis-trans eQTLs segregate within populations and evolve in close genetic linkage. PMID- 26891784 TI - Efficacy and Safety of Gabapentin vs. Carbamazepine in the Treatment of Trigeminal Neuralgia: A Meta-Analysis. AB - To evaluate the safety and efficacy of gabapentin in comparison with carbamazepine in the treatment of trigeminal neuralgia, a meta-analysis of randomized controlled trials was performed. Two reviewers independently selected studies, assessed study quality, and extracted data. Sixteen randomized controlled trials that included 1,331 patients were assessed. The meta-analysis showed that the total effective rate of gabapentin therapy group was similar with carbamazepine therapy group (OR = 1.600, 95% CI 1.185, 2.161, P = 0.002). While the effective rate of gabapentin therapy for 4 weeks was higher than that of carbamazepine therapy (OR = 1.495, 95% CI 1.061, 2.107, P = 0.022, heterogeneity: x2 = 7.12, P = 0.625, I2 = 0.0%), the life satisfaction improvement is also better in the gabapentin therapy group after a 4-week treatment (SMD = 0.966, 95% CI 0.583, 1.348, P < 0.001). Furthermore, our meta-analysis suggested that the adverse reaction rate of gabapentin therapy group was significantly lower than that of carbamazepine therapy group (OR = 0.312, 95% CI 0.240, 0.407, P < 0.001). In conclusion, present trials comparing gabapentin with carbamazepine are all poor in terms of methodological quality. Based on the available evidence, it is not possible to draw conclusions regarding the efficacy and side effects of gabapentin being superior to carbamazepine. PMID- 26891786 TI - Jumping for recognition: Women's ski jumping viewed as a struggle for rights. AB - With the campaign for women's participation in international and Olympic ski jumping as a practical case, sport's potential for recognition of individual rights is explored. In line with Honneth's influential ethical theory, recognition of rights refers to a mutual recognition between persons of each other as rational and responsible agents with an equal right to take part in the public formation and development of their community or practice. The argument is that women ski jumpers were entitled to compete as they had actual and/or potential capabilities and skills to contribute in the public formation and development of their sport. Their exclusion was a violation of individual rights. At a more general level, sport is discussed as a sphere for recognition of rights. It is argued that the basic principles of equal opportunity to take part and to perform make sport a particularly clear and potent sphere for such recognition, and also for the identification of rights violations. In sport, rights, or the violation of rights, are demonstrated in concrete and embodied ways. It is concluded that struggles for recognition and individual rights are a continuous process in sport as in most other human institutions and practices. PMID- 26891785 TI - Stability of Routine Biochemical Analytes in Whole Blood and Plasma From Lithium Heparin Gel Tubes During 6-hr Storage. AB - BACKGROUND: The stability of biochemical analytes has already been investigated, but results strongly differ depending on parameters, methodologies, and sample storage times. We investigated the stability for many biochemical parameters after different storage times of both whole blood and plasma, in order to define acceptable pre- and postcentrifugation delays in hospital laboratories. METHODS: Twenty-four analytes were measured (Modular(r) Roche analyzer) in plasma obtained from blood collected into lithium heparin gel tubes, after 2-6 hr of storage at room temperature either before (n = 28: stability in whole blood) or after (n = 21: stability in plasma) centrifugation. Variations in concentrations were expressed as mean bias from baseline, using the analytical change limit (ACL%) or the reference change value (RCV%) as acceptance limit. RESULTS: In tubes stored before centrifugation, mean plasma concentrations significantly decreased after 3 hr for phosphorus (-6.1% [95% CI: -7.4 to -4.7%]; ACL 4.62%) and lactate dehydrogenase (LDH; -5.7% [95% CI: -7.4 to -4.1%]; ACL 5.17%), and slightly decreased after 6 hr for potassium (-2.9% [95% CI: -5.3 to -0.5%]; ACL 4.13%). In plasma stored after centrifugation, mean concentrations decreased after 6 hr for bicarbonates (-19.7% [95% CI: -22.9 to -16.5%]; ACL 15.4%), and moderately increased after 4 hr for LDH (+6.0% [95% CI: +4.3 to +7.6%]; ACL 5.17%). Based on RCV, all the analytes can be considered stable up to 6 hr, whether before or after centrifugation. CONCLUSION: This study proposes acceptable delays for most biochemical tests on lithium heparin gel tubes arriving at the laboratory or needing to be reanalyzed. PMID- 26891787 TI - PAEDIATRIC NECK MULTIDETECTOR COMPUTED TOMOGRAPHY: THE EFFECT OF BISMUTH SHIELDING ON THYROID DOSE AND IMAGE QUALITY. AB - This study investigated the effect of bismuth shielding on thyroid dose and image quality in paediatric neck multidetector computed tomography (MDCT) performed with fixed tube current (FTC) and automatic exposure control (AEC). Four paediatric anthropomorphic phantoms representing the equivalent newborn, 1-, 5- and 10-y-old child were subjected to neck CT using a 16-slice MDCT system. Each scan was performed without and with single- and double-layered bismuth shield placed on the skin surface above the thyroid. Scans were repeated with cotton spacers of 1, 2 and 3 cm thick placed between the skin and shield, to study the effect of skin-to-shielding distance on image noise. Thyroid dose was measured with thermoluminescent dosemeters. The location of the thyroid within the phantom slices was determined by anthropometric data from patients' CT examinations whose body stature closely matched the phantoms. Effective dose (E) was estimated using the dose-length product (DLP) method. Image quality of resulted CT images was assessed through the image noise. Activation of AEC was found to decrease the thyroid dose by 46 % to the 10-y-old phantom subjected to neck CT. When FTC technique is used, single- and double-layered bismuth shielding was found to reduce the thyroid dose to the same phantom by 35 and 47 %, respectively. The corresponding reductions in AEC-activated scans were 60 and 66 %, respectively. Elevation of shields by 1-, 2- and 3-cm cotton spacers decreased the image noise by 69, 87 and 92 %, respectively, for single-layered FTC, without considerably affecting the thyroid dose. AEC was more effective in thyroid dose reduction than in-plane bismuth shields. Application of cotton spacers had no significant impact on thyroid dose, but significantly decreased the image noise. PMID- 26891788 TI - A REVIEW OF TWO METHODS USED IN THE USA TO ASSESS HE DURING FLUOROSCOPIC-BASED RADIOLOGY. AB - Dosemeter results for ~81 500 people performing fluoroscopic and interventional radiology procedures were examined to identify differences between groups monitored either by using two dosemeters, one placed at the collar above the apron and a second placed under the apron on the torso (EDE1) or by using one single dosemeter placed at the collar above the apron (EDE2). The median annual HE was 0.17 mSv for those monitored using the EDE1 protocol and 0.26 mSv for the group using the EDE2 protocol. The EDE2 method was used most frequently with the EDE1 method preferred for those more highly exposed. Approximately, 22 % of dosemeter results for EDE1 were inconsistent with expected norms based on over and under apron dosemeter relationships. PMID- 26891789 TI - Letter to the Editor. PMID- 26891790 TI - COMPARISON STUDY OF VARIOUS PLASTICS AS THE WALL MATERIAL OF THGEM-BASED MICRODOSEMETERS FOR FAST NEUTRON MEASUREMENTS. AB - To find appropriate substitutions for the expensive plastics of A-150 and rexolite used in the construction of thick gas electron multiplier (THGEM)-based tissue-equivalent proportional counters, in the present work, the responses of a THGEM-based microdosimetric detector made of A-150 and rexolite and three others composed of plexiglas (PMMA), polyethylene and polystyrene plastics as the wall materials have been compared. Lineal energy distribution, frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose equivalent for 0.1, 1 and 10 MeV neutrons and also for 241Am-Be neutrons are calculated using Geant4 simulation toolkit. Frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent values for all plastics are found similar. In addition, the response of an indigenously constructed microdosemeter with PMMA walls is also measured for 241Am-Be neutrons. The experimental results are in good agreement with the simulation predictions. Conclusively, it was found that the three considered plastics can be used as good candidates instead of A-150 and rexolite plastics in fast neutron microdosimetry. PMID- 26891791 TI - DOSIMETRIC VARIATION IN HUMAN EXPOSURE TO 20 MHZ-3 GHZ ELECTROMAGNETIC FIELDS DUE TO CHANGES IN DIELECTRIC PROPERTIES. AB - Specific energy absorption rate (SAR) is often used to assess human exposure to electromagnetic radiation. SAR is strongly related to incident field parameters, characteristics of the body exposed, ground effects and other factors. In this study, changes in dielectric properties, due to health and age status, were taken into account in the simulation of SAR in a Chinese male model exposed to eight orthogonal plane-wave configurations at the frequency range of 20 MHz-3 GHz. The results show that changes in dielectric properties can cause variations in SAR. Moreover, the variation in SAR was influenced by frequency, electric polarisation and incident direction. Therefore, it is of great significance to distinguish the frequency and exposure configuration when a change in dielectric properties is applied in the evaluation of SAR. In addition, more general cases with a random change in dielectric properties should be performed, which are more realistic. PMID- 26891792 TI - Calcium modulation of doxorubicin cytotoxicity in yeast and human cells. AB - Doxorubicin is a widely used chemotherapeutic agent, but its utility is limited by cellular resistance and off-target effects. To understand the molecular mechanisms regulating chemotherapeutic responses to doxorubicin, we previously carried out a genomewide search of doxorubicin-resistance genes in Schizosaccharomyces pombe fission yeast and showed that these genes are organized into networks that counteract doxorubicin cytotoxicity. Here, we describe the identification of a subgroup of doxorubicin-resistance genes that, when disrupted, leads to reduced tolerance to exogenous calcium. Unexpectedly, we observed a suppressive effect of calcium on doxorubicin cytotoxicity, where concurrent calcium and doxorubicin treatment resulted in significantly higher cell survival compared with cells treated with doxorubicin alone. Conversely, inhibitors of voltage-gated calcium channels enhanced doxorubicin cytotoxicity in the mutants. Consistent with these observations in fission yeast, calcium also suppressed doxorubicin cytotoxicity in human breast cancer cells. Further epistasis analyses in yeast showed that this suppression of doxorubicin toxicity by calcium was synergistically dependent on Rav1 and Vph2, two regulators of vacuolar-ATPase assembly; this suggests potential modulation of the calcium doxorubicin interaction by fluctuating proton concentrations within the cellular environment. Thus, the modulatory effects of drugs or diet on calcium concentrations should be considered in doxorubicin treatment regimes. PMID- 26891793 TI - Evaluation of the relative accuracy of anthropometric indicators to assess body fatness as measured by air displacement plethysmography in Indian women. AB - OBJECTIVE: To assess the relative accuracy of anthropometric indicators of body fatness or adiposity as compared to the percent fat measured by air displacement plethysmography in Indian women with normal body mass index (BMI). METHODS: Percent body fat was assessed using the BodPod in 58 women, aged 30-56 years. The relative accuracy of anthropometric indicators of body fatness like BMI, waist stature-ratio (WSR), waist-thigh-ratio (WTR), waist-hip-ratio (WHR), and circumferences at arm, neck, chest, waist, hip, and thigh were tested using an ROC curve analysis. RESULTS: Seventy-nine percent women had excess body fat (>=30%). Among the 10 indicators tested, BMI and arm circumference (AC) demonstrated high accuracy (AUC > 0.9) to assess body fatness with derived cutoffs of 21.2 kg/m(2) and 24.2 cm, respectively. WSR and circumferences at neck, chest, waist, hip, and thigh showed moderate accuracy to assess body fatness, whereas WHR and WTR demonstrated poor accuracy. CONCLUSIONS: BMI and AC were the best performing indicators of adiposity among the indicators studied. AC, being a single measurement, is practical and a good choice. Am. J. Hum. Biol. 28:743-745, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26891795 TI - Lossless Airy Surface Polaritons in a Metamaterial via Active Raman Gain. AB - We propose a scheme to realize a lossless propagation of linear and nonlinear Airy surface polaritons (SPs) via active Raman gain (ARG). The system we suggest is a planar interface superposed by a negative index metamaterial (NIMM) and a dielectric, where three-level quantum emitters are doped. By using the ARG from the quantum emitters and the destructive interference effect between the electric and magnetic responses from the NIMM, we show that not only the Ohmic loss of the NIMM but also the light absorption of the quantum emitters can be completely eliminated. As a result, non-diffractive Airy SPs may propagate for very long distance without attenuation. We also show that the Kerr nonlinearity of the system can be largely enhanced due to the introduction of the quantum emitters and hence lossless Airy surface polaritonic solitons with very low power can be generated in the system. PMID- 26891794 TI - Metabolomics in diabetic complications. AB - With a global prevalence of 9%, diabetes is the direct cause of millions of deaths each year and is quickly becoming a health crisis. Major long-term complications of diabetes arise from persistent oxidative stress and dysfunction in multiple metabolic pathways. The most serious complications involve vascular damage and include cardiovascular disease as well as microvascular disorders such as nephropathy, neuropathy, and retinopathy. Current clinical analyses like glycated hemoglobin and plasma glucose measurements hold some value as prognostic indicators of the severity of complications, but investigations into the underlying pathophysiology are still lacking. Advancements in biotechnology hold the key to uncovering new pathways and establishing therapeutic targets. Metabolomics, the study of small endogenous molecules, is a powerful toolset for studying pathophysiological processes and has been used to elucidate metabolic signatures of diabetes in various biological systems. Current challenges in the field involve correlating these biomarkers to specific complications to provide a better prediction of future risk and disease progression. This review will highlight the progress that has been made in the field of metabolomics including technological advancements, the identification of potential biomarkers, and metabolic pathways relevant to macro- and microvascular diabetic complications. PMID- 26891796 TI - Head to head comparison of the propensity score and the high-dimensional propensity score matching methods. AB - BACKGROUND: Comparative performance of the traditional propensity score (PS) and high-dimensional propensity score (hdPS) methods in the adjustment for confounding by indication remains unclear. We aimed to identify which method provided the best adjustment for confounding by indication within the context of the risk of diabetes among patients exposed to moderate versus high potency statins. METHOD: A cohort of diabetes-free incident statins users was identified from the Quebec's publicly funded medico-administrative database (Full Cohort). We created two matched sub-cohorts by matching one patient initiated on a lower potency to one patient initiated on a high potency either on patients' PS or hdPS. Both methods' performance were compared by means of the absolute standardized differences (ASDD) regarding relevant characteristics and by means of the obtained measures of association. RESULTS: Eight out of the 18 examined characteristics were shown to be unbalanced within the Full Cohort. Although matching on either method achieved balance within all examined characteristic, matching on patients' hdPS created the most balanced sub-cohort. Measures of associations and confidence intervals obtained within the two matched sub-cohorts overlapped. CONCLUSION: Although ASDD suggest better matching with hdPS than with PS, measures of association were almost identical when adjusted for either method. Use of the hdPS method in adjusting for confounding by indication within future studies should be recommended due to its ability to identify confounding variables which may be unknown to the investigators. PMID- 26891797 TI - Study on LOC426217 as a candidate gene for beak deformity in chicken. AB - BACKGROUND: The beak deformity (crossed beaks) was found in some indigenous chickens of China, such as Beijing-You (BJY), Qingyuan Partridge, and Huxu Chickens. Birds with deformed beaks have reduced feed intake and drinking, impeded growth rate, and poor production performance. Beak deformity reduces the economy of poultry industry and affects animal welfare as well. The genetic basis of this malformation remains incompletely understood. LOC426217, also named claw keratin-like, was the most up-regulated gene in the deformed beaks from a previous digital gene expression (DGE) analysis and was selected as an important candidate gene for further analysis. RESULTS: In the present study, quantitative real-time PCR (qRT-PCR) was firstly performed to determine the expression pattern of LOC426217 gene in deformed and normal beaks to verify the DGE results. Tissue specific expression profile of this gene in 14 tissues was also determined using qRT-PCR. The LOC426217 was amplified from the genomic DNA of 171 deformed and 164 normal beaks, and sequenced to detect the single nucleotide polymorphisms (SNPs). The results showed that LOC426217 was significantly high-expressed in the deformed beaks, which was in good agreement with the DGE results. This gene was specifically high-expressed in beaks than other tissues. Eight SNPs were detected in LOC426217: -62G > T, 24 T > C, 36G > C, 192A > T, 204C > T, 222 T > C, 285G > T, and 363 T > C. Genotype frequency of G-62 T, T24C, G36C, T222C, and T363C loci was significant different between deformed and normal beaks. Haplotype analysis revealed one block with SNPs T24C and G36C, and one block with SNPs A192T, C204T, T222C, and G285T in normal birds, while the block with SNPs G36C and A192T in deformed ones. CONCLUSIONS: It was concluded from these results that the over expression of LOC426217 in the beak maybe related to the malformation. The polymorphisms of LOC426217 gene were associated with the beak deformity trait where the SNPs of G-62 T, T24C, G36C, T222C, and T363C loci maybe used as markers. The specific haplotype block in deformed birds may be a potential linkage marker for this trait. PMID- 26891799 TI - A simple interfacial pH detection method for cationic amphiphilic self-assemblies utilizing a Schiff-base molecule. AB - A simple pH-sensing method for cationic micelle and vesicle interfaces is introduced, utilizing a Schiff-base molecule, 2-((4H-1,2,4-triazol-4 ylimino)methyl)-6-(hydroxymethyl)-4-methylphenol (AH). AH containing a phenolic moiety was obtained by the reaction between 4-amino-4H-1,2,4-triazole containing polar O- and N-centres with opposite polarity to the cationic interface and 2 hydroxy-3-(hydroxymethyl)-5-methylbenzaldehyde. The acid/base equilibrium of AH was investigated at the interfaces of cetrimonium bromide (CTAB) micelles, tri block-copolymeric micelles (TBPs) and large unilamellar vesicles (LUVs) of different lipid compositions using steady state UV-Vis absorption spectroscopy. AH interacted strongly with the micelle and vesicle interfaces, according to the binding studies with LUV. A larger amount of AH proton dissociation was observed when localized at the interface of micelles and vesicles compared to that in the bulk phase, indicating that the pH values at the cationic interfaces are higher than in the bulk phase. The pH values were about 2.2 and 1.6 units higher at the CTAB and TBP micelle interfaces, respectively, than the bulk pH. The pH variation decreased from 2.4 to 1.5 units by increasing the neutral 1,2-dioleoyl-sn-glycero 3-phosphocholine (DOPC) lipid content from 0 to 50% in the cationic dimethyldioctadecylammonium (DDAB) LUV, indicating that the interfacial positive charges are responsible for the higher interfacial pH. Detailed structural and absorption characteristics of neutral AH and its anionic A(-) forms were investigated by fluorescence spectroscopic measurements and DFT based theoretical calculations. The present simple pH detection method may be applied to various biological micelle and vesicle interfaces. PMID- 26891801 TI - E2F1 promotes tumor cell invasion and migration through regulating CD147 in prostate cancer. AB - Increased expression of E2F1 has been reported to be associated with tumor growth and cell survival of prostate cancer (PCa). However, its roles and mechanisms on PCa have not been fully elucidated. The present study found that E2F1 overexpression in PCa tissues was significantly associated with high Gleason score (P=0.01) and advanced pathological stage (P=0.02). In addition, PCa patients with high E2F1 expression more frequently had shorter biochemical recurrence-free survival (P=0.047) than those with low E2F1 expression. Then, we confirmed that the knock-down of E2F1 expression was able to inhibit cell cycle progression, invasion and migration of PCa cell lines in vitro, along with tumor xenograft growth and epithelial-to-mesenchymal transition (EMT) in vivo. Moreover, we identified CD147 as a novel interaction partner for E2F1 through bio informatic binding site prediction, combined with chromatin immunoprecipitation PCR (ChIP-PCR) and western blot analysis. Taken together, our data delineate an as yet unrecognized function of E2F1 as enhancer of tumor invasion and migration of PCa via regulating the expression of CD147 in PCa. Importantly, E2F1 may function as a biomarker that can differentiate patients with biochemical recurrent and non-biochemical recurrent disease following radical prostatectomy, highlighting its potential as a therapeutic target. PMID- 26891800 TI - Patients and gastroenterologists' perceptions of treatments for inflammatory bowel diseases: do their perspectives match? AB - BACKGROUND: Perceptions of appropriateness of treatments may differ between gastroenterologists (GIs) and inflammatory bowel disease (IBD) patients. The aim of this study was to explore and compare GIs' and patients' perceptions of risks and benefits of treatments and prioritization of expected outcomes. METHODS: Four vignette cases were drawn from clinical situations and used in three independent focus groups with GIs (n = 7), ulcerative colitis (UC-p, n = 8) and Crohn's disease patients (CD-p, n = 6). Content analysis was performed based on the conversation transcripts. RESULTS: UC-p agreed more often with GIs' treatment choices than CD-p. CD-p often considered 5-ASA as a placebo. UC-p saw topical 5 ASA as a temporary solution, neither comfortable nor practical when professionally active. Azathioprine was considered as the treatment for which the risks versus benefits were perceived as the highest. The main risk perceived by patients on anti-TNFs was a potential loss of response. Divergences were observed on 1) stop of treatment: UC-p did not easily concur with stopping a treatment, which differed from GIs' expectation of patients' perceptions; CD-p were more prone to consider stopping treatment than GIs, 2) perception of outcomes: physicians had a focus on long-term objective goals. Patients' expectations were of shorter term and mainly concerned stress management, nutritional advice, and information on the treatments effects. CONCLUSIONS: Overall, patients and GIs agreed on perceptions of IBD treatments. GIs seemed more concerned about objective and scientific measures of remission whereas patients focused on quality of life and social outcomes when it came to evaluating a therapy. PMID- 26891802 TI - In vivo drug metabolite identification in preclinical ADME studies by means of UPLC/TWIMS/high resolution-QTOF MS(E) and control comparison: cost and benefit of vehicle-dosed control samples. AB - 1. Liquid chromatography (LC)-high resolution mass spectrometry (HRMS) techniques proved to be well suited for the identification of predicted and unexpected drug metabolites in complex biological matrices. 2. To efficiently discriminate between drug-related and endogenous matrix compounds, however, sophisticated postacquisition data mining tools, such as control comparison techniques are needed. For preclinical absorption, distribution, metabolism and excretion (ADME) studies that usually lack a placebo-dosed control group, the question arises how high-quality control data can be yielded using only a minimum number of control animals. 3. In the present study, the combination of LC-traveling wave ion mobility separation (TWIMS)-HRMS(E) and multivariate data analysis was used to study the polymer patterns of the frequently used formulation constituents polyethylene glycol 400 and polysorbate 80 in rat plasma and urine after oral and intravenous administration, respectively. 4. Complex peak patterns of both constituents were identified underlining the general importance of a vehicle dosed control group in ADME studies for control comparison. Furthermore, the detailed analysis of administration route, blood sampling time and gender influences on both vehicle peak pattern as well as endogenous matrix background revealed that high-quality control data is obtained when (i) control animals receive an intravenous dose of the vehicle, (ii) the blood sampling time point is the same for analyte and control sample and (iii) analyte and control samples of the same gender are compared. PMID- 26891798 TI - Comparative analysis of plant immune receptor architectures uncovers host proteins likely targeted by pathogens. AB - BACKGROUND: Plants deploy immune receptors to detect pathogen-derived molecules and initiate defense responses. Intracellular plant immune receptors called nucleotide-binding leucine-rich repeat (NLR) proteins contain a central nucleotide-binding (NB) domain followed by a series of leucine-rich repeats (LRRs), and are key initiators of plant defense responses. However, recent studies demonstrated that NLRs with non-canonical domain architectures play an important role in plant immunity. These composite immune receptors are thought to arise from fusions between NLRs and additional domains that serve as "baits" for the pathogen-derived effector proteins, thus enabling pathogen recognition. Several names have been proposed to describe these proteins, including "integrated decoys" and "integrated sensors". We adopt and argue for "integrated domains" or NLR-IDs, which describes the product of the fusion without assigning a universal mode of action. RESULTS: We have scanned available plant genome sequences for the full spectrum of NLR-IDs to evaluate the diversity of integrations of potential sensor/decoy domains across flowering plants, including 19 crop species. We manually curated wheat and brassicas and experimentally validated a subset of NLR-IDs in wild and cultivated wheat varieties. We have examined NLR fusions that occur in multiple plant families and identified that some domains show re-occurring integration across lineages. Domains fused to NLRs overlap with previously identified pathogen targets confirming that they act as baits for the pathogen. While some of the integrated domains have been previously implicated in disease resistance, others provide new targets for engineering durable resistance to plant pathogens. CONCLUSIONS: We have built a robust reproducible pipeline for detecting variable domain architectures in plant immune receptors across species. We hypothesize that NLR-IDs that we revealed provide clues to the host proteins targeted by pathogens, and that this information can be deployed to discover new sources of disease resistance. PMID- 26891803 TI - Corrigendum. PMID- 26891805 TI - Gastrophysics of the Oral Cavity. AB - BACKGROUND: Gastrophysics is the science that pertains to the physical and physico-chemical description of the empirical world of gastronomy, with focus on sensory perception in the oral cavity and how it is related to the materials properties of food and cooking processes. Flavor (taste and smell), mouthfeel, chemesthesis, and astringency are all related to the chemical properties and the texture of the food and how the food is transformed in the oral cavity. METHODS: The present topical review will primarily focus attention on the somatosensory perception of food (mouthfeel or texture) and how it interacts with basic tastes (sour, bitter, sweet, salty, and umami) and chemesthetic action. RESULTS: Issues regarding diet, nutrition, and health will be put into an evolutionary perspective, and some mention will be made of umami and its importance for (oral) health. PMID- 26891804 TI - Genomic profiling of the genes on chromosome 3p in sporadic clear cell renal cell carcinoma. AB - Somatic mutations of the BRCA1 associated protein-1 (BAP1) gene, which maps to 3p21, have been found in several tumors including malignant mesothelioma, uveal melanoma, and renal cell carcinoma (RCC). The role of BAP1 inactivation in tumor development remains unclear. It has been reported that Vhl knock-out mice did not develop RCC, but Vhl knock-out mice with single allele loss of Bap1 in nephron progenitor cells developed RCC, indicating that Bap1 inactivation may be essential in murine renal tumorigenesis. To clarify the role of BAP1 in human RCC development, we performed mutation analyses, including copy number detection of BAP1 and assessment of allelic imbalance using microsatellite polymorphisms on 3p, in 45 RCC samples derived from 45 patients without VHL or BAP1 germline mutation. Additionally, we analyzed the sequences of the VHL, PBRM1, and SETD2 genes, and examined promoter methylation of VHL. Using immunostaining, we also checked for expression of BAP1 protein, which is normally located in the nuclei. None of the RCCs had biallelic deletion of BAP1, but five (11.1%) showed a biallelic mutation (four with a sequence-level mutation with monoallelic loss and one with a biallelic sequence-level mutation); these cells were negative for nuclear BAP1 staining. These patients had worse recurrence-free survival than the patients without a biallelic mutation (p=0.046). However, there were no significant differences in worse outcome by multivariate analysis combined with age, T stage, histological subtype, infiltration and vascular invasion. In 35 RCCs (77.8%), monoallelic loss of BAP1 was accompanied by VHL biallelic mutation or VHL promoter hypermethylation. In five RCCs (11.1%), we detected 3p loss-of heterozygosity, but the copy number of BAP1 was normal. Surprisingly, nuclear staining of BAP1 was negative in 10 out of 31 tumors (32.3%) with hemizygous normal BAP1, suggesting that haploinsufficiency may relate to RCC development. PMID- 26891806 TI - Treatment for Cancer Patients with Oral Mucositis: Assessment Based on the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer in International Society of Oral Oncology (MASCC/ISOO) in 2013 and Proposal of Possible Novel Treatment with a Japanese Herbal Medicine. AB - The cancer patients who received chemotherapy, radiotherapy, hematopoietic stem cell transplant and terminal care often have a wide range of stomatitis, which induces severe pain and limits fundamental life behaviors such as "eating, drinking and talking". In addition, oral mucositis frequently leads to systemic infection through opportunistic microorganisms, which causes extension of hospitalization. Severe oral mucositis often causes cancer patients to partially or completely discontinue/modify cancer therapy regimen, which adversely affects the curative effects of cancer. Therefore, the control of oral mucositis is important and indispensable for improvement of quality of life and prognosis. In this review, we introduce recent trends of the oral mucositis management in cancer patients, according to the following sentences; 1) pathophysiological mechanisms of oral mucositis, 2) assessment, 3) risk factors, 4) prevention and treatment, and 5) development of novel therapy for oral mucositis. PMID- 26891807 TI - Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement: Meta-Analysis of Clinical Outcomes and Cost-Effectiveness. AB - OBJECTIVE: Transcatheter aortic valve implantation (TAVI) has emerged as a feasible alternative treatment to conventional surgical aortic valve replacement (AVR) for high-risk patients with aortic stenosis. The present systematic review aimed to assess the comparative clinical and cost-effectiveness outcomes of TAVI versus AVR, and meta-analyse standardized clinical endpoints. METHODS: An electronic search was conducted on 9 online databases to identify all relevant studies. Eligible studies had to report on either periprocedural mortality or incremental cost-effectiveness ratio (ICER) to be included for analysis. RESULTS: The systematic review identified 24 studies that reported on comparative clinical outcomes, including three randomized controlled trials and ten matched observational studies involving 7906 patients. Meta-analysis demonstrated no significant differences in regards to mortality, stroke, myocardial infarction or acute renal failure. Patients who underwent TAVI were more likely to experience major vascular complications or arrhythmias requiring permanent pacemaker insertion. Patients who underwent AVR were more likely to experience major bleeding. Eleven analyses from 7 economic studies reported on ICER. Six analyses defined TAVI to be low value, 2 analyses defined TAVI to be intermediate value, and three analyses defined TAVI to be high value. CONCLUSION: The present study demonstrated no significant differences in regards to mortality or stroke between the two therapeutic procedures. However, the cost-effectiveness and long-term efficacy of TAVI may require further investigation. Technological improvement and increased experience may broaden the clinical indication for TAVI for low intermediate risk patients in the future. PMID- 26891808 TI - Oxidative Stress, Sarcopenia, Antioxidant Strategies and Exercise: Molecular Aspects. AB - Sarcopenia could be currently defined as a geriatric syndrome initially characterized by a decrease in muscle mass that will get worse causing deterioration in strength and physical performance. A negative protein turnover, impaired mitochondrial dynamics and functions, a decreased muscle regeneration capacity, as well as an exacerbation of apoptosis are usually considered to be cellular mechanisms involved in muscle atrophy leading to sarcopenia. In this review, we first present that muscle overproduction of reactive oxygen and nitrogen species (RONS) and oxidative stress observed during aging are associated with sarcopenia, and then discuss how RONS are involved in redox-sensitive signaling pathways leading to sarcopenia. The identification of cost effectiveness interventions to maintain muscle mass and physical functions in the elderly is one of the most important public health challenges. Here, we also discuss about the efficiency of different kind of antioxidant strategies against sarcopenia. Since exercise is the best strategy to prevent and reverse sarcopenia, we also highlight that exercise acts as an antioxidant. PMID- 26891809 TI - Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis. AB - INTRODUCTION: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. AREAS COVERED: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). EXPERT OPINION: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis. PMID- 26891810 TI - Quantitative analysis of factor P (Properdin) in monkey serum using immunoaffinity capturing in combination with LC-MS/MS. AB - AIM: Factor P (Properdin), an endogenous glycoprotein, plays a key role in innate immune defense. Its quantification is important for understanding the pharmacodynamics (PD) of drug candidate(s). RESULTS: In the present work, an immunoaffinity capturing LC-MS/MS method has been developed and validated for the first time for the quantification of factor P in monkey serum with a dynamic range of 125 to 25,000 ng/ml using the calibration standards and QCs prepared in factor P depleted monkey serum. The intra- and inter-run precision was <=7.2% (CV) and accuracy within +/-16.8% (%Bias) across all QC levels evaluated. Results of other evaluations (e.g., stability) all met the acceptance criteria. CONCLUSION: The validated method was robust and implemented in support of a preclinical PK/PD study. PMID- 26891812 TI - Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells. AB - The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis. PMID- 26891813 TI - Assessment of cosmetic ingredients in the in vitro reconstructed human epidermis test method EpiSkinTM using HPLC/UPLC-spectrophotometry in the MTT-reduction assay. AB - Cosmetics Europe recently established HPLC/UPLC-spectrophotometry as a suitable alternative endpoint detection system for measurement of formazan in the MTT reduction assay of reconstructed human tissue test methods irrespective of the test system involved. This addressed a known limitation for such test methods that use optical density for measurement of formazan and may be incompatible for evaluation of strong MTT reducer and/or coloured chemicals. To build on the original project, Cosmetics Europe has undertaken a second study that focuses on evaluation of chemicals with functionalities relevant to cosmetic products. Such chemicals were primarily identified from the Scientific Committee on Consumer Safety (SCCS) 2010 memorandum (addendum) on the in vitro test EpiSkinTM for skin irritation testing. Fifty test items were evaluated in which both standard photometry and HPLC/UPLC-spectrophotometry were used for endpoint detection. The results obtained in this study: 1) provide further support for Within Laboratory Reproducibility of HPLC-UPLC-spectrophotometry for measurement of formazan; 2) demonstrate, through use a case study with Basazol C Blue pr. 8056, that HPLC/UPLC-spectrophotometry enables determination of an in vitro classification even when this is not possible using standard photometry and 3) addresses the question raised by SCCS in their 2010 memorandum (addendum) to consider an endpoint detection system not involving optical density quantification in in vitro reconstructed human epidermis skin irritation test methods. PMID- 26891811 TI - CD4+ T-cell epitope prediction using antigen processing constraints. AB - T-cell CD4+ epitopes are important targets of immunity against infectious diseases and cancer. State-of-the-art methods for MHC class II epitope prediction rely on supervised learning methods in which an implicit or explicit model of sequence specificity is constructed using a training set of peptides with experimentally tested MHC class II binding affinity. In this paper we present a novel method for CD4+ T-cell eptitope prediction based on modeling antigen processing constraints. Previous work indicates that dominant CD4+ T-cell epitopes tend to occur adjacent to sites of initial proteolytic cleavage. Given an antigen with known three-dimensional structure, our algorithm first aggregates four types of conformational stability data in order to construct a profile of stability that allows us to identify regions of the protein that are most accessible to proteolysis. Using this profile, we then construct a profile of epitope likelihood based on the pattern of transitions from unstable to stable regions. We validate our method using 35 datasets of experimentally measured CD4+ T cell responses of mice bearing I-Ab or HLA-DR4 alleles as well as of human subjects. Overall, our results show that antigen processing constraints provide a significant source of predictive power. For epitope prediction in single-allele systems, our approach can be combined with sequence-based methods, or used in instances where little or no training data is available. In multiple-allele systems, sequence-based methods can only be used if the allele distribution of a population is known. In contrast, our approach does not make use of MHC binding prediction, and is thus agnostic to MHC class II genotypes. PMID- 26891814 TI - Evaluation of the genotoxicity/mutagenicity and antigenotoxicity/antimutagenicity induced by propolis and Baccharis dracunculifolia, by in vitro study with HTC cells. AB - The ethanolic extract of propolis, especially the Brazilian green type, is widely and mainly used for therapeutic purposes despite the lack of knowledge about its effects and its cellular mode of action. This type of propolis, derived from Baccharis dracunculifolia (alecrim-do-campo), has been extensively commercialized and the consumers use it to enhance health. This work aimed to assess the genotoxic/mutagenic and antigenotoxic/antimutagenic potentials of the ethanolic extracts of Brazilian green propolis and of B. dracunculifolia, on mammalian cells. It was not observed genotoxic and mutagenic effects by both extracts. After evaluate the exposure of the cells to each extract with a recognized mutagen, simultaneously, the results showed a significant reduction on DNA damage. The experiment carried out with a pre-incubation period was more effective than without incubation test, showing that the tested extracts were able to inactivate the mutagen before it could react with the DNA. PMID- 26891815 TI - Potential role of autophagy in smokeless tobacco extract-induced cytotoxicity and in morin-induced protection in oral epithelial cells. AB - Toxic components of STE induced serious, adverse human oral health outcomes. In the present study, we observed that STE was involved in oral toxicity by reducing the viability of human squamous epithelial cells, SCC-25, along with the simultaneous induction of both apoptosis and autophagic signaling. STE was also found to induce significant amount ROS generation in SCC-25 cells. The dietary flavonoid morin, found abundantly in a variety of herbs, fruits and wine, has been reported to attenuate ROS-induced pathogenesis including autophagy. In this study we designed three different treatment regimes of morin treatment, such as pre, co, and post - treatment of STE challenged SCC-25 cells. In all cases morin provided cytoprotection to STE challenged SCC-25 cells by augmenting STE induced ROS-dependent cytotoxic autophagy. Hence, morin is a potential option for antioxidant therapy in treatment of STE induced toxicity. PMID- 26891816 TI - The toxic effects of combined aflatoxins and zearalenone in naturally contaminated diets on laying performance, egg quality and mycotoxins residues in eggs of layers and the protective effect of Bacillus subtilis biodegradation product. AB - The toxic effect of aflatoxins (AF) and zearalenone (ZEA) and their combination on laying performance, egg quality and toxins residues in eggs, as well as the efficacy of Bacillus subtilis biodegradation product (BDP) for ameliorating these effects in layers were evaluated. Layers were submitted to a two phase experiment. The first phase was an intoxication period (18-23 wk) with birds fed 7 (3 * 2 + 1) diets (3 treatments with mycotoxins: AF (123.0 MUg/kg), ZEA (260.2 MUg/kg), or AF + ZEA (123.0 + 260.2 MUg/kg); 2 treatments with or without BDP (1000 g/t); and a control group contained no toxins nor BDP). The next phase was a recovery period (24-29 wk) in which birds were fed a toxin-free diet. In the intoxication period, AF and AF + ZEA groups exhibited lower egg production, feed intake and shell thickness, and higher AFB1, AFB2 and AFM1 residues as compared with the control group. In addition, AF and ZEA exerted synergistic effects on egg production and feed intake. Moreover, AF alone or combined with ZEA had a continuous toxic effect on laying performance in the recovery phase. Addition of BDP offset these negative effects, showing that BDP has a protective effect on layers fed contaminated diets. PMID- 26891817 TI - Molecular modeling of lipid probes and their influence on the membrane. AB - In this review a number of Molecular Dynamics simulation studies are discussed which focus on the understanding of the behavior of lipid probes in biomembranes. Experiments often use specialized probe moieties or molecules to report on the behavior of a membrane and try to gain information on the membrane as a whole from the probe lipids as these probes are the only things an experiment sees. Probes can be used to make NMR, EPR and fluorescence accessible to the membrane and use fluorescent or spin-active moieties for this purpose. Clearly membranes with and without probes are not identical which makes it worthwhile to elucidate the differences between them with detailed atomistic simulations. In almost all cases these differences are confined to the local neighborhood of the probe molecules which are sparsely used and generally present as single molecules. In general, the behavior of the bulk membrane lipids can be qualitatively understood from the probes but in most cases their properties cannot be directly quantitatively deduced from the probe behavior. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26891818 TI - Computational studies of transport in ion channels using metadynamics. AB - Molecular dynamics simulations have played a fundamental role in numerous fields of science by providing insights into the structure and dynamics of complex systems at the atomistic level. However, exhaustive sampling by standard molecular dynamics is in most cases computationally prohibitive, and the time scales accessible remain significantly shorter than many biological processes of interest. In particular, in the study of ion channels, realistic models to describe permeation and gating require accounting for large numbers of particles and accurate interaction potentials, which severely limits the length of the simulations. To overcome such limitations, several advanced methods have been proposed among which is metadynamics. In this algorithm, an external bias potential to accelerate sampling along selected collective variables is introduced. This bias potential discourages visiting regions of the configurational space already explored. In addition, the bias potential provides an estimate of the free energy as a function of the collective variables chosen once the simulation has converged. In this review, recent contributions of metadynamics to the field of ion channels are discussed, including how metadynamics has been used to search for transition states, predict permeation pathways, treat conformational flexibility that underlies the coupling between gating and permeation, or compute free energy of permeation profiles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26891819 TI - The 5-HT2A serotonin receptor in executive function: Implications for neuropsychiatric and neurodegenerative diseases. AB - Executive function entails the interplay of a group of cognitive processes enabling the individual to anticipate consequences, attain self-control, and undertake appropriate goal-directed behaviour. Serotonin signalling at serotonin 2A receptors (5-HT2AR) has important effects on these behavioural and cognitive pathways, with the prefrontal cortex (PFC) as the central actor. Indeed, the 5 HT2ARs are highly expressed in PFC, where they modulate cortical activity and local network oscillations (brain waves). Numerous psychiatric and neurodegenerative diseases result in disrupted executive function. Animal and human studies have linked these disorders with alterations in the 5-HT2AR system, making this an important pharmacological target for the treatment of disorders with impaired cognitive function. This review aims to describe the current state of knowledge on the role of 5-HT2AR signalling in components of executive function, and how 5-HT2AR systems may relate to executive dysfunctions occurring in psychiatric and neurodegenerative diseases. We hope thereby to provide insight into how pharmacotherapy targeting the 5-HT2AR may ameliorate (or exacerbate) aspects of these disorders. PMID- 26891821 TI - Reply by Authors. PMID- 26891820 TI - Special Section. PMID- 26891822 TI - Should Psychological Assessment be a Part of Incontinence Management in Children and Adolescents? PMID- 26891823 TI - Chronic venlafaxine treatment fails to alter the levels of galanin system transcripts in normal rats. AB - It is widely accepted that efficacy and speed of current antidepressants' therapeutic effect are far from optimal. Thus, there is a need for the development of antidepressants with new mechanisms of action. The neuropeptide galanin and its receptors (GalR1, GalR2 and GalR3) are among the promising targets. However, it is not clear whether or not the galanin system is involved in the antidepressant effect exerted by the currently much used inhibitors of the reuptake of serotonin and/or noradrenaline. To answer this question we administered the selective serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine (40mg/kg/day via osmotic minipumps) to normal rats and examined the levels of the transcripts for galanin and GalR1-3 after a 3-week venlafaxine treatment in the dorsal raphe, hippocampus and frontal cortex. These areas are known to be involved in the effects of antidepressants and in depression itself. Venlafaxine failed to alter the expression of any of the galanin system genes in these areas. Our results show that one of the most efficient, currently used SNRIs does not alter transcript levels of galanin or its three receptors in normal rats. These findings suggest that the pro- and antidepressive-like effects of galanin reported in animal experiments may employ a novel mechanism(s). PMID- 26891824 TI - Acute Increase in Intraocular Pressure in a Patient With a Glaucoma Drainage Implant. PMID- 26891825 TI - Neurons that detect interocular conflict during binocular rivalry revealed with EEG. AB - When the two eyes view incompatible images, perception alternates between them. What neural computations underlie this binocular rivalry? Perceptual alternations may simply reflect competition between the sets of monocular neurons that respond to each image, with the stronger driving perception. Here, we test an alternative hypothesis, that the computations that resolve rivalry make use of an active signal that reflects interocular conflict. Images presented to each eye were flickered at different frequencies while we measured steady-state visually evoked potentials (SSVEP). Signals at frequencies that are combinations of the two input frequencies can arise only from binocular neurons. In a first experiment, we measured energy at these "intermodulation" frequencies during binocular rivalry and found it to be highest immediately before rivalry restarted following a period of incomplete resolution of rivalry (a "mixed" percept). This suggests that the intermodulation signals may arise from neurons important for resolving the conflict between the two eyes' inputs. In a second experiment, we tested whether the intermodulation signal arose from neurons that measure interocular conflict by parametrically increasing conflict while simultaneously reducing image contrast. The activity of neurons that receive input from both eyes but are not sensitive to conflict should reduce monotonically as contrast decreases. The intermodulation response, however, peaked at intermediate levels of conflict, suggesting that it arises in part from neurons that respond to interocular conflict. Binocular rivalry appears to depend on an active mechanism that detects interocular conflict, whose levels of activity can be measured by the intermodulation frequencies of the SSVEP. PMID- 26891826 TI - The effect of supine body position on human heading perception. AB - The use of virtual environments in functional imaging experiments is a promising method to investigate and understand the neural basis of human navigation and self-motion perception. However, the supine position in the fMRI scanner is unnatural for everyday motion. In particular, the head-horizontal self-motion plane is parallel rather than perpendicular to gravity. Earlier studies have shown that perception of heading from visual self-motion stimuli, such as optic flow, can be modified due to visuo-vestibular interactions. With this study, we aimed to identify the effects of the supine body position on visual heading estimation, which is a basic component of human navigation. Visual and vestibular heading judgments were measured separately in 11 healthy subjects in upright and supine body positions. We measured two planes of self-motion, the transverse and the coronal plane, and found that, although vestibular heading perception was strongly modified in a supine position, visual performance, in particular for the preferred head-horizontal (i.e., transverse) plane, did not change. This provides behavioral evidence in humans that direction estimation from self-motion consistent optic flow is not modified by supine body orientation, demonstrating that visual heading estimation is one component of human navigation that is not influenced by the supine body position required for functional brain imaging experiments. PMID- 26891827 TI - Sensitivity of vergence responses of 5- to 10-week-old human infants. AB - Infants have been shown to make vergence eye movements by 1 month of age to stimulation with prisms or targets moving in depth. However, little is currently understood about the threshold sensitivity of the maturing visual system to such stimulation. In this study, 5- to 10-week-old human infants and adults viewed a target moving in depth as a triangle wave of three amplitudes (1.0, 0.5, and 0.25 meter angles). Their horizontal eye position and the refractive state of both eyes were measured simultaneously. The vergence responses of the infants and adults varied at the same frequency as the stimulus at the three tested modulation amplitudes. For a typical infant of this age, the smallest amplitude is equivalent to an interocular change of approximately 2 degrees of retinal disparity, from nearest to farthest points. The infants' accommodation responses only modulated reliably to the largest stimulus, while adults responded to all three amplitudes. Although the accommodative system appears relatively insensitive, the sensitivity of the vergence responses suggests that subtle cues are available to drive vergence in the second month after birth. PMID- 26891830 TI - Detection of between-eye differences in color: Interactions with luminance. AB - Between-eye differences in color or luminance result in the appearance of luster, which provides a cue for detecting between-eye differences. We measured thresholds for detecting between-eye differences in both hue and chromatic contrast (saturation) in dichoptically superimposed color patches. Sensitivity was found to be highest at isoluminance and decreased with the addition of task irrelevant, spatially coextensive, binocular (i.e., same in both eyes) luminance contrast. However, when the members of each dichoptic pair were presented side by side on the screen and viewed with the same eye, the added luminance contrast had no effect on the detection of their differences. If the effect of the luminance contrast was simply to dilute or desaturate the chromatic signals, we would expect thresholds to increase for the within-eye and not just the between-eye (dichoptic) conditions. We suggest that the presence of binocular luminance contrast reduces the interocular suppression between the dichoptic colors, causing the dichoptic color pairs to blend, thus rendering their differences harder to detect. PMID- 26891829 TI - Tracking the changing feature of a moving object. AB - The mind can track not only the changing locations of moving objects, but also their changing features, which are often meaningful for guiding action. How does the mind track such features? Using a task in which observers tracked the changing orientation of a rolling wheel's spoke, we found that this ability is enabled by a highly feature-specific process which continuously tracks the orientation feature itself--even during occlusion, when the feature is completely invisible. This suggests that the mental representation of a changing orientation feature and its moving object are continuously transformed and updated, akin to studies showing continuous tracking of an object's boundaries alone. We also found a systematic error in performance, whereby the orientation was reliably perceived to be further ahead than it truly was. This effect appears to occur because during occlusion the mental representation of the feature is transformed beyond the veridical position, perhaps in order to conservatively anticipate future feature states. PMID- 26891831 TI - Effect of motion discontinuities on discrimination of periodic trajectories. AB - Many biologically important motions are described by periodic trajectories. Radial frequency (RF) trajectories are one example, in which the motion of a difference of Gaussians (DOG) target moves along a path described by a sinusoidal deviation of the radius from a perfect circle (Or, Thabet, Wilkinson, & Wilson, 2011). Here we explore the hypothesis that visual processing of RF trajectories involves global spatio-temporal processes that are disrupted by motion discontinuity. To test this hypothesis, RF trajectories were used that interspersed smooth, continuous motion with three or four discontinuous jumps to other portions of the trajectory. These jumps were arranged so that the entire trajectory was traversed in the same amount of time as in the continuous motion control condition. The motion discontinuities increased thresholds by a factor of approximately 2.1 relative to continuous motion. This result provides support for global spatio-temporal processing of RF motion trajectories. Comparison with previous results suggests that motion discontinuities erase memory for earlier parts of the trajectory, thereby causing thresholds to be based on only the final segment viewed. Finally, it is shown that RF trajectories obey the 1/3 power law characteristic of biological motion. PMID- 26891832 TI - Equal-magnitude size-weight illusions experienced within and between object categories. AB - In the size-weight illusion (SWI), small objects feel heavier than larger objects of the same mass. This effect is typically thought to be a consequence of the lifter's expectation that the large object will outweigh the small object, because objects of the same type typically get heavier as they get larger. Here, we show that this perceptual effect can occur across object category, where there are no strong expectations about the correspondence between size and mass. One group of participants lifted same-colored large and small cubes with the same mass as one another, while another group lifted differently-colored large and small cubes with the same mass as one another. The group who lifted the same colored cubes experienced a robust SWI and initially lifted the large object with more force than the small object. By contrast, the group who lifted the different colored objects did so with equal initial forces on the first trial, but experienced just as strong an illusion as those who lifted the same-colored objects. These results demonstrate that color cues can selectively influence the application of fingertip force rates while not impacting at all upon the lifter's perception of object weight, highlighting a stark dissociation in how prior information affects perception and action. PMID- 26891828 TI - Multisensory simultaneity judgment and proximity to the body. AB - The integration of information across different sensory modalities is known to be dependent upon the statistical characteristics of the stimuli to be combined. For example, the spatial and temporal proximity of stimuli are important determinants with stimuli that are close in space and time being more likely to be bound. These multisensory interactions occur not only for singular points in space/time, but over "windows" of space and time that likely relate to the ecological statistics of real-world stimuli. Relatedly, human psychophysical work has demonstrated that individuals are highly prone to judge multisensory stimuli as co-occurring over a wide range of time--a so-called simultaneity window (SW). Similarly, there exists a spatial representation of peripersonal space (PPS) surrounding the body in which stimuli related to the body and to external events occurring near the body are highly likely to be jointly processed. In the current study, we sought to examine the interaction between these temporal and spatial dimensions of multisensory representation by measuring the SW for audiovisual stimuli through proximal-distal space (i.e., PPS and extrapersonal space). Results demonstrate that the audiovisual SWs within PPS are larger than outside PPS. In addition, we suggest that this effect is likely due to an automatic and additional computation of these multisensory events in a body-centered reference frame. We discuss the current findings in terms of the spatiotemporal constraints of multisensory interactions and the implication of distinct reference frames on this process. PMID- 26891833 TI - Management of skull fractures in children less than 1 year of age. AB - BACKGROUND: Management of skull fracture (SF) in pediatric patients varies from observation in the emergency department (ED) to floor admission. Since 2010, a protocol for admitting children with SF specifically to the trauma service was implemented at our institution. The purpose of our study was to review the management of children with SF younger than 1 year of age. METHODS: Retrospective chart review of all patients between 0 and 1year of age seen in our ED for a SF was done from 2010 to 2013. RESULTS: A total of 180 patients with a mean age of 4.5months (1day-12months) were identified. Of these, 131 patients (73%) were admitted. Mean length of stay was 1.6days. Admitted patients had more depressed (21 vs. 8%) and diastatic (43 vs. 14%) fractures. Fifty-seven children had intracranial hemorrhages (32%) but only 8 patients required non-emergent surgery for depressed fractures. Admission to the trauma service increased from none to 76% with phone follow-ups increasing from 12% to 91%. CONCLUSIONS: Instituting a protocol allowed a safer management of patients with SF. Moreover, we argue that asymptomatic infants with isolated SF can be safely discharged home after brief observation in the ED. PMID- 26891834 TI - The contribution of practice variation to length of stay for children with perforated appendicitis. AB - BACKGROUND: Postoperative length of stay (pLOS) is an easily tracked outcome that reflects health care efficiency and resource utilization. The purpose of this study was to determine the contribution of practice variation on pLOS for children with perforated appendicitis. METHODS: Children ages 2-18years with appendectomy for complicated appendicitis were selected from the National Surgical Quality Improvement Program-Pediatric. Extended pLOS (EpLOS) was defined as >=7days (75th percentile). The contribution of comorbidities, operative traits, and postoperative complications to EpLOS was evaluated using regression models and matched subgroup analyses. RESULTS: Of 2585 children with complicated appendicitis in our study, 835 had EpLOS. Regression analysis found that EpLOS was associated with extended operative time (odds ratio (OR) 1.99; 95% confidence interval (CI) 1.63-2.44), dehiscence (OR 13.19; 95% CI 1.52-114.23), wound infection (OR 7.39; 95% CI 2.63-20.80), organ space infection (OR 92.51; 95% CI 34.03-251.50), and pneumonia (OR 4.55; 95% CI 1.06-19.44). Over three-fourths of the variation in pLOS could not be explained by preoperative, intraoperative, or postoperative factors. CONCLUSIONS: There is significant variation in pLOS for children undergoing appendectomy that is not accounted for by comorbidities, operative traits, or complications indicating an opportunity to improve outcomes through modifying practice patterns. PMID- 26891835 TI - Fecal calprotectin in the prediction of postoperative recurrence of Crohn's disease in children and adolescents. AB - BACKGROUND: Fecal calprotectin (FC) correlates with endoscopic recurrence of Crohn's disease (CD) in adults but has not been studied among children postoperatively. We aimed to analyze whether FC relates with postoperative CD recurrence in children. METHODS: Altogether 51 postoperative endoscopies and FC measurements from 22 patients having undergone surgery for CD at age <=18years were included. RESULTS: Ileocecal resection (n=15), small bowel resection (n=6), or left hemicolectomy (n=1) was performed at median age of 15.1 (interquartile range 14.4-17.6) years. Following surgery, FC decreased significantly (659 vs. 103MUg/g, p=0.001). During median follow-up of 5.7 (4.2-7.7) years, either endoscopic or histological recurrence occurred in 17 patients (77%). FC >139MUg/g at time of endoscopy or FC increase of 79MUg/g compared to first postoperative value was suggestive of endoscopic recurrence (Rutgeerts score i2-i4), while FC >101MUg/g or increase of 21MUg/g indicated histological recurrence. Best accuracy for prediction of recurrence was obtained by combining FC at endoscopy and the postoperative increase of FC. The corresponding AUROC values were 0.74 (95% 0.58 0.89) for endoscopic recurrence whereas 0.81 (95% CI 0.67-0.95) for histological recurrence. CONCLUSION: FC is a useful surrogate marker of postoperative recurrence also in pediatric CD patients. PMID- 26891836 TI - Effectiveness and mode of action of a combination therapy for heterotopic ossification with a retinoid agonist and an anti-inflammatory agent. AB - Heterotopic ossification (HO) consists of ectopic cartilage and bone formation following severe trauma or invasive surgeries, and a genetic form of it characterizes patients with Fibrodysplasia Ossificans Progressiva (FOP). Recent mouse studies showed that HO was significantly inhibited by systemic treatment with a corticosteroid or the retinoic acid receptor gamma agonist Palovarotene. Because these drugs act differently, the data raised intriguing questions including whether the drugs affected HO via similar means, whether a combination therapy would be more effective or whether the drugs may hamper each other's action. To tackle these questions, we used an effective HO mouse model involving subcutaneous implantation of Matrigel plus rhBMP2, and compared the effectiveness of prednisone, dexamathaosone, Palovarotene or combination of. Each corticosteroid and Palovarotene reduced bone formation at max doses, and a combination therapy elicited similar outcomes without obvious interference. While Palovarotene had effectively prevented the initial cartilaginous phase of HO, the steroids appeared to act more on the bony phase. In reporter assays, dexamethasone and Palovarotene induced transcriptional activity of their respective GRE or RARE constructs and did not interfere with each other's pathway. Interestingly, both drugs inhibited the activity of a reporter construct for the inflammatory mediator NF-kappaB, particularly in combination. In good agreement, immunohistochemical analyses showed that both drugs markedly reduced the number of mast cells and macrophages near and within the ectopic Matrigel mass and reduced also the number of progenitor cells. In sum, corticosteroids and Palovarotene appear to block HO via common and distinct mechanisms. Most importantly, they directly or indirectly inhibit the recruitment of immune and inflammatory cells present at the affected site, thus alleviating the effects of key HO instigators. PMID- 26891838 TI - Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis. AB - BACKGROUND: Aggrecan degradation is the hallmark of cartilage degeneration in osteoarthritis (OA), though it is unclear whether a common proteolytic process occurs in all individuals. METHODS: Aggrecan degradation in articular cartilage from the knees of 33 individuals with OA, who were undergoing joint replacement surgery, was studied by immunoblotting of tissue extracts. RESULTS: Matrix metalloproteinases (MMPs) and aggrecanases are the major proteases involved in aggrecan degradation within the cartilage, though the proportion of aggrecan cleavage attributable to MMPs or aggrecanases was variable between individuals. However, aggrecanases were more associated with the increase in aggrecan loss associated with OA than MMPs. While the extent of aggrecan cleavage was highly variable between individuals, it was greatest in areas of cartilage adjacent to sites of cartilage erosion compared to sites more remote within the same joint. Analysis of link protein shows that in some individuals additional proteolytic mechanisms must also be involved to some extent. CONCLUSIONS: The present studies indicate that there is no one protease, or a fixed combination of proteases, responsible for cartilage degradation in OA. Thus, rather than targeting the individual proteases for OA therapy, directing research to techniques that control global protease generation may be more productive. PMID- 26891837 TI - Discovery of novel polyamine analogs with anti-protozoal activity by computer guided drug repositioning. AB - Chagas disease is a parasitic infection caused by the protozoa Trypanosoma cruzi that affects about 6 million people in Latin America. Despite its sanitary importance, there are currently only two drugs available for treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects and limited efficacy in the chronic stage of the disease. Polyamines are ubiquitous to all living organisms where they participate in multiple basic functions such as biosynthesis of nucleic acids and proteins, proliferation and cell differentiation. T. cruzi is auxotroph for polyamines, which are taken up from the extracellular medium by efficient transporters and, to a large extent, incorporated into trypanothione (bis-glutathionylspermidine), the major redox cosubstrate of trypanosomatids. From a 268-compound database containing polyamine analogs with and without inhibitory effect on T. cruzi we have inferred classificatory models that were later applied in a virtual screening campaign to identify anti-trypanosomal compounds among drugs already used for other therapeutic indications (i.e. computer-guided drug repositioning) compiled in the DrugBank and Sweetlead databases. Five of the candidates identified with this strategy were evaluated in cellular models from different pathogenic trypanosomatids (T. cruzi wt, T. cruzi PAT12, T. brucei and Leishmania infantum), and in vitro models of aminoacid/polyamine transport assays and trypanothione synthetase inhibition assay. Triclabendazole, sertaconazole and paroxetine displayed inhibitory effects on the proliferation of T. cruzi (epimastigotes) and the uptake of putrescine by the parasite. They also interfered with the uptake of others aminoacids and the proliferation of infective T. brucei and L. infantum (promastigotes). Trypanothione synthetase was ruled out as molecular target for the anti-parasitic activity of these compounds. PMID- 26891839 TI - HPTN 068: A Randomized Control Trial of a Conditional Cash Transfer to Reduce HIV Infection in Young Women in South Africa-Study Design and Baseline Results. AB - Young women in South Africa are at high risk for HIV infection. Cash transfers offer promise to reduce HIV risk. We present the design and baseline results from HPTN 068, a phase III, individually randomized trial to assess the effect of a conditional cash transfer on HIV acquisition among South African young women. A total of 2533 young women were randomized to receive a monthly cash transfer conditional on school attendance or to a control group. A number of individual-, partner-, household- and school-level factors were associated with HIV and HSV-2 infection. After adjusting for age, all levels were associated with an increased odds of HIV infection with partner-level factors conveying the strongest association (aOR 3.05 95 % CI 1.84-5.06). Interventions like cash transfers that address structural factors such as schooling and poverty have the potential to reduce HIV risk in young women in South Africa. PMID- 26891841 TI - Molecular characterisation of a novel recombinant Ribgrass mosaic virus strain FSHS. AB - BACKGROUND: The genus Tobamovirus (Virgaviridae) comprises 33 accepted species with the recent addition of eight new viruses and is divided in to three subgroups based on the origin of assembly of the virion and host range. Within the subgroup 1 tobamoviruses the orchid-associated tobamovirus was hypothesized to be a chimeric derivative of recombinations between genome fragments from subgroup 3 and 1. Recombination events involving RdRp, movement and coat protein genes are recorded within subgroup 1 and 2. However natural recombinations have not previously been reported between subgroup 3 tobamoviruses. FINDINGS: The organization and phylogenetic analyses of the complete genome and the different ORFs placed the new isolate within the Ribgrass mosaic virus clade of subgroup 3 tobamoviruses. Recombination detection analyses indicated that the isolate was a chimeric genome with fragments of high similarity to Ribgrass mosaic virus (RMV) strains NZ-439 (HQ667978) and Actinidia-AC (GQ401365.1) infecting herbaceous Plantago sp. and woody Actinidia spp., respectively. The recombinant differed across the whole genome by 3-8 % from other published RMV genomes. CONCLUSION: In this investigation we report an intra-specific recombination between RMV strains NZ-439 (HQ667978) and Actinidia-AC (GQ401365.1), in the replicase component between viral-methyltransferase and viral-helicase regions, resulting in a novel RMV strain FSHS (JQ319720.1) that represents the first described natural recombinant within the RMV cluster of subgroup 3 tobamoviruses. PMID- 26891842 TI - The development of an evidenced-based and clinically trialled Oral Health Protocol for Paediatric Oncology Patients at the Women's and Children's Hospital, Adelaide, South Australia. PMID- 26891840 TI - Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support. AB - Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting ("beneficiary") and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts. PMID- 26891843 TI - Medical advocacy among African-American women diagnosed with breast cancer: from recipient to resource. AB - PURPOSE: Medical advocacy at multiple levels (self, community/interpersonal, national/public health interest) may be helpful to address the disproportionate burden of breast cancer African-American women encounter. Little, however, is known about the interplay of medical advocacy at different levels. METHODS: We analyzed qualitative data from two studies focused on the psychosocial experiences of breast cancer among 38 African-American women living in Western Washington State. RESULTS: Emergent themes suggested that survivors received community/interpersonal advocacy from different members of social networks in the form of social support (appraisal, emotional, informational, instrumental). Survivors indicated that receiving this support was associated with greater self advocacy in terms of their own care experiences, as well as greater community/interpersonal advocacy on their part as resources to other women diagnosed with breast cancer, their family, friends, and larger communities. CONCLUSION: Our findings suggest that community/interpersonal advocacy, including providing different types of support, may lead to improved self-advocacy as well as health-protective impacts for the networks in which survivors are embedded. Future quantitative research is warranted to support these findings and assess how this interplay is associated with improved outcomes among this marginalized and resilient population. PMID- 26891844 TI - Plasma Levels of Endothelial Microparticles Bearing Monomeric C-reactive Protein are Increased in Peripheral Artery Disease. AB - C-reactive protein (CRP) as an indicator of cardiovascular disease (CVD) has shown limited sensitivity. We demonstrate that two isoforms of CRP (pentameric, pCRP and monomeric, mCRP) present in soluble form or on microparticles (MPs) have different biological effects and are not all measured by clinical CRP assays. The high-sensitivity CRP assay (hsCRP) did not measure pCRP or mCRP on MPs, whereas flow cytometry did. MPs derived from endothelial cells, particularly those bearing mCRP, were elevated in peripheral artery disease (PAD) patients compared to controls. The numbers of mCRP(+) endothelial MPs did not correlate with hsCRP measurements of soluble pCRP, indicating their independent modulation. In controls, statins lowered mCRP(+) endothelial MPs. In a model of vascular inflammation, mCRP induced endothelial shedding of MPs and was proinflammatory, while pCRP was anti-inflammatory. mCRP on endothelial MPs may be both an unmeasured indicator of, and an amplifier of, vascular disease, and its detection might improve risk sensitivity. PMID- 26891846 TI - Editorial. Biobanking Eggs and Embryos for Research. PMID- 26891848 TI - Plasmodium falciparum histidine rich protein-2 diversity and the implications for PfHRP 2: based malaria rapid diagnostic tests in Ghana. AB - BACKGROUND: Malaria rapid diagnostic tests (RDTs) play a key role in malaria management and control. The PfHRP-2 based RDT is the most widely used RDT for malaria diagnosis in Ghana. Deletion of pfhrp2 in Plasmodium falciparum parasites affect the diagnostic accuracy of PfHRP-2 based RDT kits. Identifying the prevalence and distribution of P. falciparum parasites with deleted pfhrp2 is important for malaria control. AIM: The purpose of this study was to identify and confirm the prevalence of pfhrp2 deletant P. falciparum parasites circulating within different regions of Ghana. METHODS: DNA was extracted from the membrane of spent CareStartTM PfHRP-2 RDT kits and dried filter paper blood blots using Chelex-100. Exon 2 of pfhrp2 and pfhrp3 genes were amplified by polymerase chain reaction (PCR), resolved by agarose gel electrophoresis and visualized under UV light. RESULTS: Microscopic analysis of blood smears from samples that were PfHRP 2 RDT positive revealed a parasite prevalence of 54/114 (47.4 %) and 2/26 (7.7 %) in Accra and Cape Coast, respectively. PCR analysis increased parasite prevalence in the RDT positive samples to 94/114 (82.5 %) and 6/26 (23.1 %) in Accra and Cape Coast respectively. The exon 2 of the pfhrp2 gene was deleted in 18/54 (33.3 %) of the microscopy confirmed and 36.2 % (34/94) of the PCR confirmed RDT positive samples collected in Accra. No RDT sample, confirmed to contain parasites by either PCR or microscopy was negative by pfhrp2 exon 2 PCR in Cape Coast. A survey of an additional 558 DBS revealed that 22.4 % (46/205) and 40 % (44/110) of PCR positive samples in Accra and Cape Coast, respectively, lacked the exon 2 region of pfhrp2 and possibly the entire pfhrp2 gene. CONCLUSIONS: A high number of P. falciparum parasites, which lack pfhrp2 exon 2 gene have been identified in two communities in Ghana. Continuous nationwide monitoring of the prevalence of pfhrp2 deletant parasites would be essential to malaria control. The use of RDT kits that are effective at malaria diagnosis despite deletion of pfhrp2, such as the PfHRP-2/PfLDH combo RDT kit could enhance the diagnosis of clinical malaria in Ghana. PMID- 26891845 TI - Calcific Aortic Valve Disease: Part 1--Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks. AB - Aortic valvular stenosis (AVS), produced by calcific aortic valve disease (CAVD) causing reduced cusp opening, afflicts mostly older persons eventually requiring valve replacement. CAVD had been considered "degenerative," but newer investigations implicate active mechanisms similar to atherogenesis--genetic predisposition and signaling pathways, lipoprotein deposits, chronic inflammation, and calcification/osteogenesis. Consequently, CAVD may eventually be controlled/reversed by lifestyle and pharmacogenomics remedies. Its management should be comprehensive, embracing not only the valve but also the left ventricle and the arterial system with their interdependent morphomechanics/hemodynamics, which underlie the ensuing diastolic and systolic LV dysfunction. Compared to even a couple of decades ago, we now have an increased appreciation of genomic and cytomolecular pathogenetic mechanisms underlying CAVD. Future pluridisciplinary studies will characterize better and more completely its pathobiology, evolution, and overall dynamics, encompassing intricate feedback processes involving specific signaling molecules and gene network cascades. They will herald more effective, personalized medicine treatments of CAVD/AVS. PMID- 26891847 TI - Neuregulin 1 confers neuroprotection in SOD1-linked amyotrophic lateral sclerosis mice via restoration of C-boutons of spinal motor neurons. AB - INTRODUCTION: Increasing evidence implicates the role of the cell types surrounding motor neurons, such as interneurons and glial cells, in non-cell autonomous neurodegeneration of amyotrophic lateral sclerosis (ALS). C-boutons, the large cholinergic synapses that innervate spinal alpha-motor neurons to control their excitability, are progressively lost from motor neurons in both human ALS and mutant Cu/Zn superoxide dismutase 1 (SOD1)-ALS mice. Neuregulin-1 (NRG1), a trophic factor implicated in neural development, transmission, and synaptic plasticity, has been reported to localize in the synapse of C-boutons. However, the roles of NRG1 in maintenance of motor neuron health and activity, as well as the functional consequences of its alteration in motor neuron disease, are not fully understood. RESULTS: NRG1 was localized to the post-synaptic face of C-boutons and its expression was significantly lost in SOD1-ALS mice and human ALS patients. Losses of NRG1 expression and C-boutons occurred almost contemporaneously in SOD1-ALS mice. In addition, expressions of ErbB3 and ErbB4, receptors for NRG1, were reduced in the motor neurons of SOD1-ALS mice. Furthermore, viral-mediated delivery of type III-NRG1 to the spinal cord restored the number of C-boutons and extended the survival time of SOD1-ALS mice. CONCLUSIONS: These results suggest that maintenance of NRG1-ErbB4/3 axis by supplementation of NRG1 confers neuroprotection in motor neuron disease, partly through the maintenance of C-boutons of spinal motor neurons. PMID- 26891849 TI - Patient characteristics and outcomes of a hip fracture and concomitant fracture compared with hip fracture alone: results from a United Kingdom teaching hospital. AB - INTRODUCTION: A proportion of patients sustaining hip fractures present with a concomitant fracture. We aimed to evaluate the relationship between patient characteristics and clinical outcomes, in those with a hip and concomitant fracture compared with those sustaining a hip fracture alone from a clinical service registry. METHOD: Cross-sectional study using data obtained from a clinical service registry (Nottingham Hip Fracture Database) on patients aged 50 and above who suffered a hip fracture between 1/1/2003 and 31/12/2012. Data was collected on patient demographics, fracture information and healthcare outcomes. RESULTS: 7338 patients of which 75 % were female (mean age 82 (SD 9.4), had a hip fracture with 334 (4.6 %) patients having a concomitant fracture. The majority (58 %) were distal radius or proximal humeral fractures. Only females (p = 0.002), those taking three or fewer medications (p = 0.018) and those on long term steroids (p = 0.048) were more likely to suffer a concomitant fracture. There was no difference in mortality, rates of postoperative complication, intensive care unit or care home admission between both groups. Patients with a concomitant fracture have a 16 % longer average length of stay in hospital (mean difference 1.16; 95 % CI 1.07-1.25, p < 0.001). CONCLUSIONS: Patients with concomitant fractures have similar patient characteristics, except gender, polypharmacy and long term steroid use; and outcomes to those presenting with hip fracture alone, except a longer average inpatient stay. PMID- 26891850 TI - Decreased femoral periprosthetic bone mineral density: a comparative study using DXA in patients after cementless total hip arthroplasty with osteonecrosis of the femoral head versus primary osteoarthritis. AB - INTRODUCTION: Trabecular properties in osteonecrosis of the femoral head (ONFH) are altered for bone volume and structure in the femoral head and proximal femoral canal. We analysed the periprosthetic bone mineral density (BMD) as a correlate to bony ingrowth in patients with ONFH who received a cementless THA. MATERIALS AND METHODS: We performed a matched-pair analysis of 100 patients with ONFH (n = 50) and primary osteoarthritis (n = 50) who received the same, unilateral cementless THA. We compared the periprosthetic BMD 5 years after surgery by means of dual energy X-ray absorptiometry (DXA) analysing the seven femoral regions of interest (ROIs) according to Gruen. RESULTS: Within the ONFH group, significantly lower BMD values were found in the ROI 1 and 7 (p < 0.05). No statistically significant difference was found for ROIs 2-6. CONCLUSIONS: An altered periprosthetic bone stock in the proximal femur in patients with prior ONFH might be a possible risk factor for premature loosening of the femoral stem in THA. Surgeons need to consider coating and fixation philosophy of cementless implants when choosing the right stem for patients with ONFH. PMID- 26891851 TI - Evidence for photo-induced charge separation between dye molecules adsorbed to aluminium oxide surfaces. AB - Excited state dynamics and photo-induced charge transfer of dye molecules have been widely studied due to their relevance for organic and dye-sensitised solar cells. Herein, we present a femtosecond transient absorption spectroscopy study of the indolene dye D131 when adsorbed to inert Al2O3 substrates for different surface concentration of the dye. Surprisingly, we find that at high surface concentrations, the first singlet excited state of the dye is converted into a new state with an efficiency of about 80%. We assign the absorption features of this state to the oxidised dye and discuss the possibility of photo-induced charge separation between neighboring dye molecules. Our study is the first to show that this process can be highly efficient without the use of donor and acceptor molecules of different chemical structures. PMID- 26891852 TI - Peer-to-Peer, Interactive GP Education can Reduce Barriers to Best Practice in Diabetes Management. AB - INTRODUCTION: Perceived difficulties in initiating insulin in patients with type 2 diabetes (T2D) may prevent many general practitioners (GPs) from using insulin even when recommended in guidelines. This paper describes a Royal Australian College of General Practitioners accredited education program on starting insulin in T2D, and its impact on GPs' attitudes and behavior. METHODS: A faculty comprising GPs with diabetes expertise, Credentialed Diabetes Nurse Educators, and endocrinologist developed and implemented the education program. The program content was highly procedure focussed, emphasizing simple, best-practice processes for starting insulin therapy and focussing on multidisciplinary models of care. The highly interactive format of the workshops included peer-to-peer learning, in which education was led by diabetes-experienced GP educators, as well as case study-based approaches and small group discussions. GP attendees were asked to rate their individual confidence and attitudes at the beginning and end of the meeting. In addition, participants (n = 220) from two workshops in 2013 were sent a survey 3 months after the meeting to gauge the longer-term impact on their clinical practice. RESULTS: Since 2008, more than 2500 GPs have attended the workshops, and report substantial improvements in confidence; after attending, more GPs were willing to start insulin within their practice. Evaluations at 3 months post-meeting indicate that the increased confidence was associated with behavioral changes in the subgroup evaluated at this time (n = 48). Success of this program was attributed to peer-to-peer education, multidisciplinary input, easily implemented best practice procedures and checklists for starting insulin, and constant adjustment of meeting process and content based on feedback and guideline changes. CONCLUSION: A peer-to-peer, interactive GP education program reduced GPs' perceptions of the difficulties of starting insulin in T2D and achieved changes in attendees' clinical practice. This education program offers an effective approach to overcome the therapeutic inertia that is too common in diabetes management. PMID- 26891853 TI - Concerning "Pathological findings in patients with low anterior inferior iliac spine impingement". PMID- 26891854 TI - Allergic rhinitis affects the duration of rapid eye movement sleep in children with sleep-disordered breathing without sleep apnea. AB - BACKGROUND: Our goals were to assess whether allergic rhinitis (AR) is an aggravating factor that affects the severity of sleep apnea in children with tonsils/adenoid hypertrophy (T&A) and to compare polysomnographic data from children with and without AR. METHODS: This prospective study included 135 children (age range, 3 to 14 years) with sleep-disordered breathing (SDB) resulting from T&A. Children with lung, neurological, or craniofacial problems; septal deviations; previous pharyngeal surgeries; or orthodontic treatments were excluded. All children underwent a clinical evaluation, nasopharyngoscopy or lateral X-ray imaging, sleep study, and hypersensitivity skin-prick test. RESULTS: The mean patient age was 6.44 +/- 2.55 years (83 males). AR was present in 42.2% of the children; 40% presented with sleep apnea; and 17.04% had sleep apnea and AR. The percentage of time spent in the rapid eye movement (REM) sleep stage was lower among children with AR without sleep apnea (p = 0.028); however, the percentage of REM sleep was not significantly different among children with apnea (p = 0.2922). No difference in the apnea-hypopnea index (AHI) was observed between the children with (AHI = 2.79 events/hour) and without AR (3.75 events/hour, p = 0.4427). A multivariate analysis showed that nasal congestion was an important factor that can affect the duration of the REM sleep stage. CONCLUSION: AR affects REM sleep in children with SDB without sleep apnea, and AR is not an aggravating factor regarding the severity of AHI. PMID- 26891855 TI - Design of Synthetic Polymer Nanoparticles That Facilitate Resolubilization and Refolding of Aggregated Positively Charged Lysozyme. AB - Designed polymer hydrogel nanoparticles (NPs) capable of facilitating resolubilization and refolding of an aggregated protein, positively charged lysozyme, are prepared. NPs designed to interact strongly with denatured lysozyme and relatively weakly with native lysozyme, facilitated resolubilization and refolding of aggregated lysozyme. Such NPs could be prepared by copolymerizing optimized combinations and populations of functional monomers. The refolded lysozyme showed native conformation and enzymatic activity. Eleven grams of aggregated protein was refolded by 1 g of NPs. However, NPs having low affinity to denatured lysozyme and NPs having high affinity to both denatured and native lysozyme showed relatively low facilitation activity. Our results suggest a potential strategy for the design of artificial chaperones with high facilitating activity. PMID- 26891858 TI - What more can TOF-SIMS bring than other MS imaging methods? PMID- 26891856 TI - Pro-oxidant and Antioxidant Effects in Photodynamic Therapy: Cells Recognise that Not All Exogenous ROS Are Alike. AB - Photodynamic therapy (PDT) uses light, photosensitizer molecules and oxygen to generate reactive oxygen species (ROS) that kill cancer cells. Redaporfin, a new photosensitizer in clinical trials, generates both singlet oxygen and superoxide ions. We report the potentiation of redaporfin-PDT in combination with ascorbate and with the inhibition of antioxidant enzymes in A549 (human lung adenocarcinoma) and CT26 (mouse colon adenocarcinoma) cells. The addition of ascorbate and the inhibition of superoxide dismutase (SOD) strongly increased the phototoxicity of redaporfin towards A549 cells but not towards CT26 cells. The inhibition of catalase and the depletion of the glutathione pool also potentiate redaporfin-PDT towards A549 cells. The lower SOD activity of A549 cells might explain this difference. SOD activity levels may be explored to increase the selectivity and efficacy of PDT with photosensitizers that generate radical species. PMID- 26891857 TI - Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria. AB - INTRODUCTION: Extended spectrum beta-lactamases (ESBL) and AmpC beta-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed. AREAS COVERED: This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly beta-lactam-beta-lactamase inhibitor combinations and cefepime (FEP). EXPERT OPINION: Based on available data, the use of piperacillin tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC beta-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally. PMID- 26891859 TI - Extracellular nucleotide regulation and signaling in cardiac fibrosis. AB - Following myocardial infarction, purinergic nucleotides and nucleosides are released via non-specific and specific mechanisms in response to cellular activation, stress, or injury. These extracellular nucleotides are potent mediators of physiologic and pathologic responses, contributing to the inflammatory and fibrotic milieu within the injured myocardium. Via autocrine or paracrine signaling, cell-specific effects occur through differentially expressed purinergic receptors of the P2X, P2Y, and P1 families. Nucleotide activation of the ionotropic (ligand-gated) purine receptors (P2X) and several of the metabotropic (G-protein-coupled) purine receptors (P2Y) or adenosine activation of the P1 receptors can have profound effects on inflammatory cell function, fibroblast function, and cardiomyocyte function. Extracellular nucleotidases that hydrolyze released nucleotides regulate the magnitude and duration of purinergic signaling. While there are numerous studies on the role of the purinergic signaling pathway in cardiovascular disease, the extent to which the purinergic signaling pathway modulates cardiac fibrosis is incompletely understood. Here we provide an overview of the current understanding of how the purinergic signaling pathway modulates cardiac fibroblast function and myocardial fibrosis. PMID- 26891860 TI - Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress. AB - Interleukin-1beta is one of the main mediators in the cross-talk between the immune system and the central nervous system. Higher interleukin-1beta levels are found in mood spectrum disorders, and the stress-induced expression rate of the interleukin-1beta gene (IL1B) is altered by polymorphisms in the region. Therefore we examined the effects of rs16944 and rs1143643 single nucleotide polymorphisms (SNPs) within the IL1B gene on depressive and anxiety symptoms, as measured by the Brief Symptom Inventory, in a Hungarian population sample of 1053 persons. Distal and proximal environmental stress factors were also included in our analysis, namely childhood adversity and recent negative life-events. We found that rs16944 minor (A) allele specifically interacted with childhood adversity increasing depressive and anxiety symptoms, while rs1143643's minor (A) allele showed protective effect against depressive symptoms after recent life stress. The genetic main effects of the two SNPs were not significant in the main analysis, but the interaction effects remained significant after correction for multiple testing. In addition, the effect of rs16944 A allele was reversed in a subsample with low-exposure to life stress, suggesting a protective effect against depressive symptoms, in the post hoc analysis. In summary, both of the two IL1B SNPs showed specific environmental stressor-dependent effects on mood disorder symptoms. We also demonstrated that the presence of exposure to childhood adversity changed the direction of the rs16944 effect on depression phenotype. Therefore our results suggest that it is advisable to include environmental factors in genetic association studies when examining the effect of the IL1B gene. PMID- 26891861 TI - Frequency of early warning score assessment and clinical deterioration in hospitalized patients: A randomized trial. AB - AIM: To explore whether early warning score (EWS) measurements at 8h intervals is associated with better outcomes than 12h intervals. We hypothesized that the proportion of patients that deteriorated to a higher EWS at 24h after hospital admission would be lower with 8h interval than with 12h interval. METHOD: This was a pragmatic, ward-level randomized, non-blinded, controlled trial at an urban University hospital. During two six weeks periods acutely admitted surgical and medical patients, with an initial EWS of 0 or 1, were monitored either every 8th hour or every 12th hour. The primary outcome was clinical deterioration 24h post admission, estimated by the proportion of patients with an EWS>=2 at 24h after the initial EWS on admission. RESULTS: Of 3185 patients screened for eligibility, 1346 patients were included to the trial. Forty-nine percent were allocated to the 8h group and 51% to the 12h group; of these, 23% and 20% had an elevated EWS>=2 at 24h, respectively (p=0.456), OR 1.17 (0.78-1.76); 3.4% and 2.2%, respectively had an EWS>=5 (p=0.391), and one patient in each group had an EWS>=7 at 24h (p=1.0). Multiple logistic regression analysis showed no significant interactions for the primary outcome and the predefined variables: age, gender, ward type, and inclusion period, with an adjusted OR 1.20 (0.79-1.82). There were no significant differences in regard to the secondary outcomes: cardiac arrests, ICU admissions, review by medical emergency team (MET), length of hospital stay, or elevated EWS at 48 h. Thirty-day mortality was 1.1% vs. 1.8% (p=0.357) in the 8h group and the 12h-group, respectively (OR=0.60 (0.23-1.50), p=0.279). CONCLUSION: We found no significant reduction in the proportion of clinical deterioration with monitoring frequencies of 3 vs. 2 times daily among patients acutely admitted to a surgical or medical ward and an initial EWS of 0-1. PMID- 26891862 TI - Automatic cardiac rhythm interpretation during resuscitation. AB - AIM: Resuscitation guidelines recommend different treatments depending on the patient's cardiac rhythm. Rhythm interpretation is a key tool to retrospectively evaluate and improve the quality of treatment. Manual rhythm annotation is time consuming and an obstacle for handling large resuscitation datasets efficiently. The objective of this study was to develop a system for automatic rhythm interpretation by using signal processing and machine learning algorithms. METHODS: Data from 302 out of hospital cardiac arrest patients were used. In total 1669 3-second artifact free ECG segments with clinical rhythm annotations were extracted. The proposed algorithms combine 32 features obtained from both wavelet- and time-domain representations of the ECG, followed by a feature selection procedure based on the wrapper method in a nested cross-validation architecture. Linear and quadratic discriminant analyses (LDA and QDA) were used to automatically classify the segments into one of five rhythm types: ventricular tachycardia (VT), ventricular fibrillation (VF), pulseless electrical activity (PEA), asystole (AS), and pulse generating rhythms (PR). RESULTS: The overall accuracy for the best algorithm was 68%. VT, VF, and AS are recognized with sensitivities of 71%, 75%, and 79%, respectively. Sensitivities for PEA and PR were 55% and 56%, respectively, which reflects the difficulty of identifying pulse using only the ECG. CONCLUSIONS: An ECG based automatic rhythm interpreter for resuscitation has been demonstrated. The interpreter handles VT, VF and AS well, while PEA and PR discrimination poses a more difficult problem. PMID- 26891863 TI - Effect of Confinement on the Properties of Sequestered Mixed Polar Solvents: Enzymatic Catalysis in Nonaqueous 1,4-Bis-2-ethylhexylsulfosuccinate Reverse Micelles. AB - The influence of different glycerol, N,N-dimethylformamide (DMF) and water mixtures encapsulated in 1,4-bis-2-ethylhexylsulfosuccinate (AOT)/n-heptane reverse micelles (RMs) on the enzymatic hydrolysis of 2-naphthyl acetate by alpha chymotrypsin is demonstrated. In the case of the mixtures with DMF and protic solvents it has been previously shown, using absorption, emission and dynamic light-scattering techniques, that solvents are segregated inside the polar core of the RMs. Protic solvents anchor to the AOT, whereas DMF locates to the polar core of the aggregate. Thus, DMF not only helps to solubilize the hydrophobic substrate, increasing its effective concentrations but surprisingly, it does not affect the enzyme activity. The importance of ensuring the presence of RMs, encapsulation of the polar solvents and the corrections by substrate partitioning in order to obtain reliable conclusions is highlighted. Moreover, the effect of a constrained environment on solvent-solvent interactions in homogenous media and its impact on the use of RMs as nanoreactors is stressed. PMID- 26891864 TI - Alkaptonuria: An example of a "fundamental disease"--A rare disease with important lessons for more common disorders. AB - "Fundamental diseases" is a term introduced by the charity Findacure to describe rare genetic disorders that are gateways to understanding common conditions and human physiology. The concept that rare diseases have important lessons for biomedical science has been recognised by some of the great figures in the history of medical research, including Harvey, Bateson and Garrod. Here we describe some of the recently discovered lessons from the study of the iconic genetic disease alkaptonuria (AKU), which have shed new light on understanding the pathogenesis of osteoarthritis. In AKU, ochronotic pigment is deposited in cartilage when collagen fibrils become susceptible to attack by homogentisic acid (HGA). When HGA binds to collagen, cartilage matrix becomes stiffened, resulting in the aberrant transmission of loading to underlying subchondral bone. Aberrant loading leads to the formation of pathophysiological structures including trabecular excrescences and high density mineralised protrusions (HDMPs). These structures initially identified in AKU have subsequently been found in more common osteoarthritis and appear to play a role in joint destruction in both diseases. PMID- 26891866 TI - Activating AMP-activated protein kinase by an alpha1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death. AB - Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel alpha1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13' cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKalpha1, or dominant negative mutation of AMPKalpha1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKalpha1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca AMPKalpha1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKalpha1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. PMID- 26891865 TI - Sphenoid sinus malignancies: a population-based comprehensive analysis. AB - BACKGROUND: Sinonasal malignancies are rare, representing less than 1% of all cancers, with the sphenoid sinus accounting for 1% to 2% of these cases. Sphenoid sinus malignancies exhibit very poor outcomes. There is a paucity of literature describing their histopathological features, incidence trends, treatment, and survival. We seek to elucidate these factors using a national population-based resource. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify malignant sphenoid sinus tumors. The results were analyzed for demographics, incidence, and clinicopathologic trends. Survival was calculated using Kaplan-Meier analysis. RESULTS: The search identified 472 cases. The mean and median age at diagnosis was 60.0 years. Males represented 54.9% of cases. By race/ethnicity, 82.4% were white and 8.5% were black. The four most common histopathologies were squamous cell neoplasms (29.4%), adenocarcinomas (14.4%), non-Hodgkin's mature B-cell lymphomas (13.1%), and unspecified epithelial neoplasms (11.0%). The overall incidence from 2000 to 2012 was 0.030 per 100,000. Kaplan-Meier analysis demonstrated an overall 5-year disease specific survival (DSS) of 48.1%. Of the most common histopathological subtypes, 5-year DSS was best for mature B-cell NHL (64.0%) and worst for unspecified epithelial neoplasms (25.6%). CONCLUSION: Sphenoid sinus malignancies are rare, with high prevalence in white males. The most common histopathology is squamous cell neoplasms. They exhibit significant locoregional extension. Of the common sphenoid sinus malignant subtypes, 5-year DSS is best for mature B-cell NHL and worst for unspecified epithelial neoplasms. PMID- 26891867 TI - Repression of a chromatin modifier aggravates lipopolysaccharide-induced acute lung injury in mouse. AB - Local inflammatory responses and alveolar epithelial cells (AECs) apoptosis are both important for the development of the acute lung injury (ALI), a clinically important complication causing high morbidity and mortality, but little is known about the molecular mechanisms underlying the pathogenesis. Herein, we showed for the first time that expression of Metastasis-associated protein 1 (MTA1), a master transcriptional regulator with the ability to regulate divergent cellular pathways by modifying the acetylation status of crucial target genes, was up regulated in the alveolar cells of the Escherichia coli lipopolysaccharide (LPS) induced murine ALI model. Inhibition of MTA1 expression by in vivo siRNA treatment exacerbated the pathology of LPS-induced ALI, by selectively promoting the expression of NF-kappaB-regulated inflammatory cytokines. Moreover, ablation of MTA1 expression promoted the LPS-induced apoptosis in AEC II cells, leaving AEC I cells unaffected. These data collectively underscore an alveolar facet of this important chromatin modifier, which may represent as a novel regulator and a new therapeutic target for the treatment of ALI. PMID- 26891868 TI - Vascular complications in diabetes: Microparticles and microparticle associated microRNAs as active players. AB - The recognition of the importance of diabetes in vascular disease has greatly increased lately. Common risk factors for diabetes-related vascular disease include hyperglycemia, insulin resistance, dyslipidemia, inflammation, hypercoagulability, hypertension, and atherosclerosis. All of these factors contribute to the endothelial dysfunction which generates the diabetic complications, both macro and microvascular. Knowledge of diabetes-related vascular complications and of associated mechanisms it is becoming increasingly important for therapists. The discovery of microparticles (MPs) and their associated microRNAs (miRNAs) have opened new perspectives capturing the attention of basic and clinical scientists for their potential to become new therapeutic targets and clinical biomarkers. MPs known as submicron vesicles generated from membranes of apoptotic or activated cells into circulation have the ability to act as autocrine and paracrine effectors in cell-to-cell communication. They operate as biological vectors modulating the endothelial dysfunction, inflammation, coagulation, angiogenesis, thrombosis, subsequently contributing to the progression of macro and microvascular complications in diabetes. More recently, miRNAs have started to be actively investigated, leading to first exciting reports, which suggest their significant role in vascular physiology and disease. The contribution of MPs and also of their associated miRNAs to the development of vascular complications in diabetes was largely unexplored and undiscussed. In essence, with this review we bring light upon the understanding of impact diabetes has on vascular biology, and the significant role of MPs and MPs associated miRNAs as novel mediators, potential biomarkers and therapeutic targets in vascular complications in diabetes. PMID- 26891869 TI - The molecular mechanisms between metabolic syndrome and breast cancer. AB - Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease. PMID- 26891870 TI - Zinc-binding protein-89 (ZBP-89) cooperates with NF-kappaB to regulate expression of matrix metalloproteinases (MMPs) in response to inflammatory cytokines. AB - Matrix metalloproteinases (MMPs) have both protective and pathological roles in inflammation, and transcriptional mechanisms are important in regulating physiological levels to maintain health. Zinc-binding protein-89 (ZBP-89) is a transcription factor with roles in regulating vital cellular processes, acting through complex interactions with other proteins to ensure appropriate expression of tightly regulated genes. ZBP-89 binds the MMP-3 promoter at a polymorphic (5A/6A) site along with NF-kappaB. This polymorphism affects MMP-3 protein levels in tissues. In disease association studies, both over- and under-expression has negative consequences to health, and this promoter element is important in maintaining balanced expression. There is evidence that effects of the polymorphism vary under different conditions, but the role of ZBP-89 in these differences is not known. ZBP-89 was stably knocked-down in MG-63 osteosarcoma cells in order to study its role in regulation of MMP-3 expression in response to cytokines, and evaluate the functionality of a putative binding site in the MMP-1 promoter. Results show ZBP-89 is needed for maximal induction of both genes by IL 1beta and TNFalpha. Binding of both ZBP-89 and NF-kappaB to both promoters was decreased in the knock-down cells under basal and TNF-induced conditions, and protein interactions between ZBP-89 and NF-kappaB were suggested. These data provide the first evidence of a role for ZBP-89 in regulation of MMP-1 expression, and suggest the possibility of a larger role for ZBP-89 in inflammation through interactions with NF-kappaB. PMID- 26891872 TI - In Vitro CYP2D Inhibitory Effect and Influence on Pharmacokinetics and Pharmacodynamic Parameters of Metoprolol Succinate by Terminalia arjuna in Rats. AB - BACKGROUND: Terminalia arjuna Wight & Arn. (Combretaceae) is a tree having an extensive medicinal potential in cardiovascular disorders. T. arjuna bark extract has been reported to play a significant role as a cardiac stimulant for its beneficial effects in angina. Herb - drug interactions (HDI) are one of the most important clinical concerns in the concomitant consumption of herbs and prescription drugs. Our study was to investigate the in vitro CYP2D inhibition potential of Terminalia arjuna (T. arjuna) extracts in rat liver microsomes and to study the influence of aqueous bark extract of T. arjuna on the oral pharmacokinetics and pharmacodynamics of metoprolol succinate in rats. METHODS: The CYP2D inhibition potential of herbal extracts of T. arjuna was investigated in rat liver microsomes. Pharmacokinetic-pharmacodynamic interaction of aqueous extract of T. arjuna with metoprolol succinate was investigated in rats. RESULTS: The ethyl acetate, alcoholic & aqueous bark extracts of T. arjuna showed potent reversible non-competitive inhibition CYP2D enzyme in rat liver microsomes with IC50 values less than 40 MUg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP2D enzyme in rat liver microsomes. Pharmacokinetic studies showed that aqueous bark extract of T. arjuna led to a significant reduction (P < 0.05) in AUC0-24h and Cmax of metoprolol succinate in rats, when co-administered. Pharmacodynamic studies reveal a significant reduction in therapeutic activity of metoprolol succinate on co-administration with aqueous bark extract of T. arjuna. CONCLUSION: Based on our in vitro and in vivo findings and until further clinical drug interaction experiments are conducted, the co-administration of drugs, especially those primarily cleared via CYP2D catalyzed metabolism, with T. arjuna extracts should be done with caution. PMID- 26891871 TI - Impact of CYP3A4*1G Allele on Clinical Pharmacokinetics and Pharmacodynamics of Clopidogrel. AB - BACKGROUND AND OBJECTIVES: Resistance to the antiplatelet treatment with clopidogrel has both genetic and non-genetic causes. Polymorphic variants of cytochrome P450 3A4 isoenzyme involved in the bioactivation of clopidogrel might have an influence on responsiveness to the drug. The aim of this study was to evaluate the influence of CYP3A4*1G (IVS10+12G>A, rs2242480) on the pharmacokinetics and pharmacodynamics of clopidogrel. METHODS: CYP3A4*1G polymorphism was determined in a group of 82 patients undergoing percutaneous coronary intervention and taking 75 mg of clopidogrel daily. Concentrations of clopidogrel and its metabolites, inactive carboxylic acid derivative and two diastereoisomers of active thiol metabolite: H3 and H4, were determined by a validated HPLC-MS/MS method. Pharmacodynamic effect was measured by an impedance method with a Multiplate analyzer. Moreover, an effect of factors, such as CYP2C19 phenotype, age, gender, body mass index and interactions with drugs metabolized by CYP3A4 were also investigated. RESULTS: In the studied group allele frequencies were: wt-0.921, *1G-0.079. Pharmacokinetic parameters of clopidogrel and its metabolites were not significantly different in carriers of *1G allele, comparing to wt/wt homozygotes. Platelet aggregation was higher in heterozygotes than in wt/wt carriers; however, the difference was not statistically significant (p = 0.484). In a multivariate analysis, which included age, body mass index, co-morbidities and coadministered drugs, CYP3A4*1G was not a predictor of values of H3 and H4 pharmacokinetic parameters and platelet aggregation. CONCLUSION: CYP3A4*1G might not be a significant contributor to the variability in pharmacokinetic and pharmacodynamic response to clopidogrel therapy. PMID- 26891873 TI - In Vitro Study of UGT Metabolism and Permeability of Orientin and Isoorientin, Two Active flavonoid C-glycosides. AB - C-glycosides are important flavonoids with significant pharmacological activities implicated in anticancer and antioxidative effects. However, their characteristics of metabolism and transportation have been rarely investigated. This research aimed to examine the metabolic characteristics of two active C glycosides, namely, orientin and isoorientin, in human liver microsomes (HLMs) and rat liver microsomes (RLMs) and to confirm the specific uridine 5'-diphospho glucuronosyltransferase (UGT) isoforms involved in glucuronidation by HLMs. Furthermore, the permeability of orientin and isoorientin was also determined by using Caco-2 cell monolayers. Results revealed that orientin and isoorientin could generate two metabolites, which were identified as monoglucuronides. HLM- and RLM-mediated glucuronide formations were in accordance with typical Michaelis Menten kinetics. Conversely, RLM initially metabolized orientin to its corresponding metabolite, and this process was consistent with biphasic kinetics. Among the UGT isoform, UGT1A1, 1A8, 1A9 and 1A10 exhibited the highest enzyme activity. Passive diffusion was the predominant orientin and isoorientin transportation mechanism in Caco-2 cell monolayers, and their apparent permeability further confirmed that orientin and isoorientin were well absorbed. Therefore, orientin and isoorientin can be metabolized by UGT isoforms and microsomes; these flavonoids can also be transported via passive diffusion in Caco-2 cells, which are relatively permeable. PMID- 26891874 TI - Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats. AB - BACKGROUND: The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. NEW METHOD: The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. RESULTS: Injection of Complete Freund's Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in male and female rats. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). COMPARISON WITH EXISTING METHODS: Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. CONCLUSIONS: The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID- 26891875 TI - Source modeling of ElectroCorticoGraphy (ECoG) data: Stability analysis and spatial filtering. AB - BACKGROUND: Electrocorticography (ECoG) measures the distribution of the electrical potentials on the cortex produced by the neural currents. A full interpretation of ECoG data requires solving the ill-posed inverse problem of reconstructing the spatio-temporal distribution of the neural currents. This study addresses the ECoG source modeling developing a beamformer method. NEW METHOD: We computed the lead-field matrix by using a novel routine provided by the OpenMEEG software. We performed an analysis of the numerical stability of the ECoG inverse problem by computing the condition number of the lead-field matrix for different configurations of the electrodes grid. We applied a Linear Constraint Minimum Variance (LCMV) beamformer to both synthetic data and a set of real measurements recorded during a rapid visual categorization task. RESULTS: For all considered grids the condition number indicates that the ECoG inverse problem is mildly ill-conditioned. For realistic SNR we found a good performance of the LCMV algorithm for both localization and waveforms reconstruction. COMPARISON WITH EXISTING METHOD: The flow of information reconstructed by analyzing real data seems consistent with both invasive monkey electrophysiology studies and non-invasive (MEG and fMRI) human studies. CONCLUSIONS: Despite a growing interest from the neuroscientific community, solving the ECoG inverse problem has not quite yet reached the level of systematicity found for EEG and MEG. Starting from an analysis of the numerical stability of the problem we considered the most widely utilized method for modeling neurophysiological data based on the beamformer method in the hope to establish benchmarks for future studies. PMID- 26891876 TI - A nationwide survey of co-occurrence of malignant lymphomas and myelodysplastic syndromes/myeloproliferative neoplasms. PMID- 26891877 TI - Leukemogenic potency of the novel FLT3-N676K mutant. AB - The novel FMS-like tyrosine kinase 3 (FLT3)-N676K point mutation within the FLT3 kinase domain-1 was recently identified in 6 % of de novo acute myeloid leukemia (AML) patients with inv(16). Because FLT3-N676K was encountered almost exclusively in inv(16) AML, we investigated the transforming potential of FLT3 N676K, the cooperation between FLT3-N676K and core binding factor beta-smooth muscle myosin heavy chain (CBFbeta-SMMHC) (encoded by the inv(16) chimeric gene CBFB-MYH11) in inducing acute leukemia, and tested the sensitivity of FLT3-N676K positive leukemic cells to FLT3 inhibitors. Retroviral expression of FLT3-N676K in myeloid 32D cells induced AML in syngeneic C3H/HeJ mice (n = 11/13, median latency 58 days), with a transforming activity similar to FLT3-internal tandem duplication (ITD) (n = 8/8), FLT3-TKD D835Y (n = 8/9), and FLT3-ITD-N676K (n = 9/9) mutations. Three out of 14 (21.4 %) C57BL/6J mice transplanted with FLT3 N676K-transduced primary hematopoietic progenitor cells developed acute leukemia (latency of 68, 77, and 273 days), while no hematological malignancy was observed in the control groups including FLT3-ITD. Moreover, co-expression of FLT3 N676K/CBFbeta-SMMHC did not promote acute leukemia in three independent experiments (n = 16). In comparison with FLT3-ITD, FLT3-N676K induced much higher activation of FLT3 and tended to trigger stronger phosphorylation of MAPK and AKT. Importantly, leukemic cells carrying the FLT3-N676K mutant in the absence of an ITD mutation were highly sensitive to FLT3 inhibitors AC220 and crenolanib, and crenolanib even retained activity against the AC220-resistant FLT3-ITD-N676K mutant. Taken together, the FLT3-N676K mutant is potent to transform murine hematopoietic stem/progenitor cells in vivo. This is the first report of acute leukemia induced by an activating FLT3 mutation in C57BL/6J mice. Moreover, further experiments investigating molecular mechanisms for leukemogenesis induced by FLT3-N676K mutation and clinical evaluation of FLT3 inhibitors in FLT3-N676K positive AML seem warranted. PMID- 26891878 TI - Tyrosine kinase inhibitors in Ph+ acute lymphoblastic leukaemia: facts and perspectives. AB - Two tyrosine kinase inhibitors (TKIs), imatinib and dasatinib, are registered for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) in adults. Other two TKIs (nilotinib and ponatinib) have been tested in the second-line, can offer an alternative in the patients who fail the first-line, and can acquire a role also in the first-line. Here, we provide a summary of the reports of TKIs, used alone, and in combination with chemotherapy. TKIs are very effective alone and with corticosteroids and are likely to improve substantially the outcome when they are combined with standard or dose-adapted chemotherapy. While the complete haematologic remission rate is always very high, close to 100 %, the cytogenetic and molecular remission rates are lower, so that TKIs are still considered as a complement to chemotherapy and as a bridge to allogeneic stem cell transplantation (allo-SCT). However, many patients relapse before transplant, and many patients still relapse, even if they have been submitted to allo-SCT. A proper use of TKIs, the introduction of ponatinib, and of "new generation" TKIs should improve further on the outcome of Ph+ ALL. PMID- 26891879 TI - Psychopharmacological interventions in autism spectrum disorder. AB - INTRODUCTION: Individuals with autism spectrum disorder (ASD) commonly present for treatment of emotional and behavioral disturbances associated with ASD's "core" symptoms. Psychotropic medications are widely utilized in alleviating associated emotional and behavioral symptoms. AREAS COVERED: Emotional and behavioral disturbances associated with ASD include irritability/severely disruptive behavior, which comprises the heaviest symptom burden; hyperactivity and other Attention-Deficit-Hyperactivity-Disorder (ADHD)-type symptoms; repetitive/stereotyped behaviors; and social withdrawal. Existing evidence for medications for each of these symptom clusters will be examined in this review. EXPERT OPINION: Psychopharmacological treatment of core and associated symptoms in ASD is challenging, in large part because of the heterogeneity in the presentation of ASD. Furthermore, children and adolescents with ASD are more vulnerable to the side effects of psychopharmacological intervention than their age-matched, typically developing counterparts. Currently, risperidone and aripiprazole are the only medications that have been (relatively) reliably shown to help treat certain symptom clusters associated with ASD, namely severely disruptive behavior and hyperactivity. Recent studies have begun to look at medications with mechanisms that are novel in the treatment of ASD and that may address underlying pathophysiology and/or core symptoms such as glutamate modulating agents. Overall, randomized, placebo-controlled studies of medications for the treatment of ASD are scarce. PMID- 26891880 TI - Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies. AB - TOPIC: Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular parameters, specifically the ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL), with the accuracy of RNFL parameters for detecting manifest glaucoma is important to guide clinical practice and future research. METHODS: Studies using spectral domain optical coherence tomography (SD OCT) and reporting macular parameters were included if they allowed the extraction of accuracy data for diagnosing manifest glaucoma, as confirmed with automated perimetry or a clinician's optic nerve head (ONH) assessment. Cross-sectional cohort studies and case-control studies were included. The QUADAS 2 tool was used to assess methodological quality. Only direct comparisons of macular versus RNFL parameters (i.e., in the same study) were conducted. Summary sensitivity and specificity of each macular or RNFL parameter were reported, and the relative diagnostic odds ratio (DOR) was calculated in hierarchical summary receiver operating characteristic (HSROC) models to compare them. RESULTS: Thirty-four studies investigated macular parameters using RTVue OCT (Optovue Inc., Fremont, CA) (19 studies, 3094 subjects), Cirrus OCT (Carl Zeiss Meditec Inc., Dublin, CA) (14 studies, 2164 subjects), or 3D Topcon OCT (Topcon, Inc., Tokyo, Japan) (4 studies, 522 subjects). Thirty-two of these studies allowed comparisons between macular and RNFL parameters. Studies generally reported sensitivities at fixed specificities, more commonly 0.90 or 0.95, with sensitivities of most best-performing parameters between 0.65 and 0.75. For all OCT devices, compared with RNFL parameters, macular parameters were similarly or slightly less accurate for detecting glaucoma at the highest reported specificity, which was confirmed in analyses at the lowest specificity. Included studies suffered from limitations, especially the case-control study design, which is known to overestimate accuracy. However, this flaw is less relevant as a source of bias in direct comparisons conducted within studies. CONCLUSIONS: With the use of OCT, RNFL parameters are still preferable to macular parameters for diagnosing manifest glaucoma, but the differences are small. Because of high heterogeneity, direct comparative or randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential. PMID- 26891881 TI - CE-MS in metabolomics: status quo and the way forward. PMID- 26891882 TI - Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S transferase pi are required for its peroxidase but not phospholipase A2 activity. AB - Peroxiredoxin 6 (Prdx6) is a unique 1-Cys member of the peroxiredoxin family with both GSH peroxidase and phospholipase A2 (PLA2) activities. It is highly expressed in the lung where it plays an important role in antioxidant defense and lung surfactant metabolism. Glutathionylation of Prdx6 mediated by its heterodimerization with GSH S-transferase pi (piGST) is required for its peroxidatic catalytic cycle. Recombinant human Prdx6 crystallizes as a homodimer and sedimentation equilibrium analysis confirmed that this protein exists as a high affinity dimer in solution. Based on measurement of molecular mass, dimeric Prdx6 that was oxidized to the sulfenic acid formed a sulfenylamide during storage. After examination of the dimer interface in the crystal structure, we postulated that the hydrophobic amino acids L145 and L148 play an important role in homodimerization of Prdx6 as well as in its heterodimerization with piGST. Oxidation of Prdx6 also was required for its heterodimerization. Sedimentation equilibrium analysis and the Duolink proximity ligation assay following mutation of the L145 and L148 residues of Prdx6 to Glu indicated greatly decreased dimerization propensity reflecting the loss of hydrophobic interactions between the protein monomers. Peroxidase activity was markedly reduced by mutation at either of the Leu sites and was essentially abolished by the double mutation, while PLA2 activity was unaffected. Decreased peroxidase activity following mutation of the interfacial leucines presumably is mediated via impaired heterodimerization of Prdx6 with piGST that is required for reduction and re activation of the oxidized enzyme. PMID- 26891886 TI - Partial-Homogeneity-Based Two-Dimensional High-Resolution Nuclear Magnetic Resonance Spectroscopy under Inhomogeneous Magnetic Fields. AB - High-resolution multidimensional nuclear magnetic resonance (NMR) spectroscopy serves as an irreplaceable and versatile tool in various chemical investigations. In this study, a method based on the concept of partial homogeneity is developed to offer two-dimensional (2D) high-resolution NMR spectra under inhomogeneous fields. Oscillating gradients are exerted to encode the high-resolution information, and a field-inhomogeneity correction algorithm based on pattern recognition is designed to recover high-resolution spectra. Under fields where inhomogeneity primarily distributes along a single orientation, the proposed method will improve performances of 2D NMR spectroscopy without increasing the experimental duration or significant loss in sensitivity, and thus may open important perspectives for studies of inhomogeneous chemical systems. PMID- 26891887 TI - Reperfusion of Retinal Vasculature With Improved Visual Acuity in Ischemic Occlusive Vasculitis. PMID- 26891888 TI - Syncope with Swallowing. AB - Swallowing can be a trigger for syncope and can cause significant morbidity and mortality if not recognized. A 13-year-old presented with clusters of transient complete atrioventricular block after repair of a sinus venosus atrial septal defect. Pacemaker implantation was successful in treating these symptoms. PMID- 26891889 TI - Nitroxide antioxidant as a potential strategy to attenuate the oxidative/nitrosative stress induced by hydrogen peroxide plus nitric oxide in cultured neurons. AB - Oxidative/nitrosative stress contributes to the etiology of the neurological disorders, including ischemic stroke and chronic neurodegeneration. Neurotoxic modifications mediated by reactive oxygen species (ROS) or reactive nitrogen species (RNS) are closely associated with the destruction of key macromolecules and inactivation of antioxidant enzymes, which compromises antioxidant defenses. Approaches to expel ROS/RNS and alleviate toxic oxidative/nitrosative stress in neurons have not completely been defined. Here, we aimed to evaluate the efficacy of various antioxidants that serve as the neuroprotectors under a toxic stress created by ROS plus nitric oxide (NO). Sublytic concentrations of hydrogen peroxide (H2O2) plus NO donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP) enabled to induce a toxic oxidative/nitrosative stress through activating both p38 MAPK and p53 cascades, and cause DNA damage and protein tyrosine nitration in primary neuronal cultures. After comparing six antioxidants, including superoxide dimutase (SOD), catalase, 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO), N acetylcysteine, dimethylthiourea, and uric acid, TEMPO was the superior antioxidant that comprehensively and efficaciously decreased H2O2 plus SNAP evoked activation of stress cascades of p38 MAPK and p53, production of NO, ROS, and peroxynitrite, double-strand breaks of DNA, and nitration of protein tyrosine residues. SOD increased the peroxynitrite formation and was unable to reduce the level of protein nitration. All antioxidants tested, except SOD, effectively reduced neuronal damage and DNA breakage caused by the toxic H2O2/SNAP combination. In conclusion, these results suggest that TEMPO ensures excellent ROS/RNS clearance and stress-signaling inhibition, thus effectively rescuing neurons from ROS/H2O2 plus NO/SNAP-induced insult. This study reveals a potential strategy for nitroxide antioxidants as a therapeutic agent against oxidative/nitrosative neurotoxicity. PMID- 26891890 TI - Nitric oxide signaling in human ovarian cancer: A potential therapeutic target. AB - Ovarian cancer is the leading cause of death due to gynecologic malignancies worldwide. Current therapy regimens are ineffective to treat advanced ovarian cancers, presenting a need to develop novel therapeutic strategies. Nitric oxide (NO) is a multifunctional gaseous molecule that is generated by cancer, stromal and endothelial cells and plays a multifaceted role in cancer biology through multiple mechanisms. Accumulating evidence suggests that NO signaling is involved in multiple aspects of ovarian cancer, including growth, apoptosis, cancer stromal cell interaction, angiogenesis and response to chemotherapy. This review will discuss the experimental and clinical evidence of the involvement of NO signaling in ovarian cancer and the therapeutic potential of targeting NO signaling in ovarian cancer. PMID- 26891891 TI - Sweet syndrome and disseminated Mycobacterium tuberculosis infection. PMID- 26891892 TI - An alternative interpretation of cellular 'selfish spermatogonial selection' clusters in the human testis indicates the need for 3-D-analyses. AB - The 'selfish spermatogonial selection'- model was proposed to explain the paternal age effect (PAE) of some congenital disorders associated with point mutations in male germ cells. According to this, spermatogonia carrying pathogenic mutations gain a selection advantage over non-mutated spermatogonia which leads to an increased number of mutated spermatogonia and consequently spermatozoa over time. Recently, an immunohistochemical approach using the premeiotic marker melanoma antigen family A4 (MAGE A4) was undertaken by the Wilkie group to confirm the presence of microclones of putatively mutated spermatogonia in testes of elderly men. The objective of our study was the age dependent assessment of testes from men with normal spermatogenesis using MAGE A4 immunohistochemistry to identify and corroborate cellular clusters indicative for 'selfish spermatogonial selection' in our cohort. We analyzed testicular tissues obtained from men with normal spermatogenesis assigned to three age groups [(1) 28.8 +/- 2.7 years; (2) 48.1 +/- 1 years; (3) 71.9 +/- 6.8 years, n/group = 8]. We could detect very similar distribution patterns of MAGE A4-positive cells and the presence of several types of microclusters as reported previously. However, these cellular clusters, indicative for clonal expansion, were not only present in testes from elderly men but also in those from age group 1 and 2. Using graphical three-dimensional modelling, we identified that cross-section directions e.g. longitudinal sections might provoke misleading interpretation of spermatogonial clusters, in particular when the tissue processing is limited. Thus, appropriate fixation and embedding is needed for reliable analysis of testicular sections. We therefore propose a more careful interpretation of such spermatogonial clusters and recommend a 3-D analysis to unequivocally determine 'selfish spermatogonial selection'-manifestations. PMID- 26891893 TI - PACO: PArticle COunting Method To Enforce Concentrations in Dynamic Simulations. AB - We present PACO, a computationally efficient method for concentration boundary conditions in nonequilibrium particle simulations. Because it requires only particle counting, its computational effort is significantly smaller than other methods. PACO enables Brownian dynamics simulations of micromolar electrolytes (3 orders of magnitude lower than previously simulated). PACO for Brownian dynamics is integrated in the BROWNIES package (www.phys.rush.edu/BROWNIES). We also introduce a molecular dynamics PACO implementation that allows for very accurate control of concentration gradients. PMID- 26891894 TI - CORR ((r)) Curriculum - Orthopaedic Education: Mentorship in Surgical Training: Can Personality Assessment Help? PMID- 26891895 TI - What Is the Impact of Center Variability in a Multicenter International Prospective Observational Study on Developmental Dysplasia of the Hip? AB - BACKGROUND: Little information exists concerning the variability of presentation and differences in treatment methods for developmental dysplasia of the hip (DDH) in children < 18 months. The inherent advantages of prospective multicenter studies are well documented, but data from different centers may differ in terms of important variables such as patient demographics, diagnoses, and treatment or management decisions. The purpose of this study was to determine whether there is a difference in baseline data among the nine centers in five countries affiliated with the International Hip Dysplasia Institute to establish the need to consider the center as a key variable in multicenter studies. QUESTIONS/PURPOSES: (1) How do patient demographics differ across participating centers at presentation? (2) How do patient diagnoses (severity and laterality) differ across centers? (3) How do initial treatment approaches differ across participating centers? METHODS: A multicenter prospective hip dysplasia study database was analyzed from 2010 to April 2015. Patients younger than 6 months of age at diagnosis were included if at least one hip was completely dislocated, whereas patients between 6 and 18 months of age at diagnosis were included with any form of DDH. Participating centers (academic, urban, tertiary care hospitals) span five countries across three continents. Baseline data (patient demographics, diagnosis, swaddling history, baseline International Hip Dysplasia Institute classification, and initial treatment) were compared among all nine centers. A total of 496 patients were enrolled with site enrolment ranging from 10 to 117. The proportion of eligible patients who were enrolled and followed at the nine participating centers was 98%. Patient enrollment rates were similar across all sites, and data collection/completeness for relevant variables at initial presentation was comparable. RESULTS: In total, 83% of all patients were female (410 of 496), and the median age at presentation was 2.2 months (range, 0-18 months). Breech presentation occurred more often in younger (< 6 months) than in older (6-18 months at diagnosis) patients (30% [96 of 318] versus 9% [15 of 161]; odds ratio [OR], 4.2; 95% confidence interval [CI], 2.3-7.5; p < 0.001). The Australia site was underrepresented in breech presentation in comparison to the other centers (8% [five of 66] versus 23% [111 of 479]; OR, 0.3, 95% CI, 0.1-0.7; p = 0.034). The largest diagnostic category was < 6 months, dislocated reducible (51% [253 of 496 patients]); however, the Australia and Boston sites had more irreducible dislocations compared with the other sites (ORs, 2.1 and 1.9; 95% CIs, 1.2-3.6 and 1.1-3.4; p = 0.02 and 0.015, respectively). Bilaterality was seen less often in older compared with younger patients (8% [seven of 93] versus 26% [85 of 328]; p < 0.001). The most common diagnostic group was Grade 3 (by International Hip Dysplasia Institute classification), which included 58% (51 of 88) of all classified dislocated hips. Splintage was the primary initial treatment of choice at 80% (395 of 496), but was far more likely in younger compared with older patients (94% [309 of 328] versus 18% [17 of 93]; p < 0.001). CONCLUSIONS: With the lack of strong prognostic indicators for DDH identified to date, the center is an important variable to include as a potential predictor of treatment success or failure. PMID- 26891897 TI - Obituary: A Remembrance of George E. Omer Jr. MD (1922-2014). PMID- 26891883 TI - Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury. AB - There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury. PMID- 26891896 TI - How Does Wear Rate Compare in Well-functioning Total Hip and Knee Replacements? A Postmortem Polyethylene Liner Study. AB - BACKGROUND: The longevity of total hip (THR) and knee replacements (TKR) that used historical bearing materials of gamma-in-air sterilized UHMWPE was affected more by osteolysis in THRs than in TKRs, although osteolysis remains a concern in TKRs. Therefore, the study of polyethylene wear is still of interest for the knee, particularly because few studies have investigated volumetric material loss in tibial knee inserts. For this study, a unique collection of autopsy-retrieved TKR and THR components that were well-functioning at the time of retrieval was used to compare volumetric wear differences between hip and knee polyethylene components made from identical material. QUESTIONS/PURPOSES: The following questions were addressed: (1) How much did the hip liners wear and what wear patterns did they exhibit? (2) How much did the knee inserts wear and what wear patterns did they exhibit? (3) What is the ratio between TKR and THR wear after controlling for implantation time and patient age? METHODS: We compared 23 THR components (Harris-Galante [HG] and HG II) and 20 TKR components (Miller-Galante [MG II]) that were retrieved postmortem. The components were made from the same polyethylene formulation and with similar manufacturing and sterilization (gamma in-air) processes. Twenty-one patients (12 males, nine females) had THRs and 16 (four males, 12 females) had TKRs. Patients who had TKRs had an older (p = 0.001) average age than patients who had THRs (age, 75 years; SD, 10, versus 66 years; SD, 12, respectively). Only well-functioning components were included in this study. Therefore, implants retrieved postmortem from physically active patients and implanted for at least 2 years were considered. In addition, only normally wearing TKR components were considered, ie, those with fatigue wear (delamination) were excluded. The wear volume of each component was measured using metrology. For the tibial inserts an autonomous mathematic reconstruction method was used for quantification. RESULTS: The acetabular liners of the THR group had a wear rate of 38 mm(3) per year (95% CI, 29-47 mm(3)/year). Excluding patients with low-activity, the wear rate was 47 mm(3) per year (95% CI, 37-56 mm(3)/year). The wear rate of normally wearing tibial inserts was 17 mm(3) per year (95% CI, -6 to 40 mm(3)/year). After controlling for the relevant confounding variable of age, we found a TKR/THR wear rate ratio of 0.5 (95% CI, 0.29-0.77) at 70 years of age with a slightly increasing difference with increasing age. CONCLUSIONS: Excluding delamination, TKRs exhibited lower articular wear rates than THRs for historical polyethylene in these two unique cohorts of postmortem retrievals. CLINICAL RELEVANCE: The lower TKR wear rate is in line with the lower incidence of osteolysis in TKRs compared with THRs. PMID- 26891898 TI - Does Preadmission Cutaneous Chlorhexidine Preparation Reduce Surgical Site Infections After Total Hip Arthroplasty? AB - BACKGROUND: Periprosthetic hip infections are among the most catastrophic complications after total hip arthroplasty (THA). We had previously proven that the use of chlorhexidine cloths before surgery may help decrease these infections; hence, we increased the size of the previously reported cohort. QUESTIONS/PURPOSES: (1) Does a preadmission chlorhexidine cloth skin preparation protocol decrease the risk of surgical site infection in patients undergoing THA? (2) When stratified using the National Healthcare Safety Network (NHSN) risk categories, which categories are associated with risk reduction from the preadmission chlorhexidine preparation protocol? METHODS: Between 2007 and 2013, a group of 998 patients used chlorhexidine cloths before surgery, whereas a group of 2846 patients did not use them and underwent standard perioperative disinfection only. Patient records were reviewed to determine the development of periprosthetic infection in both groups of patients. RESULTS: Patients without the preoperative chlorhexidine gluconate disinfection protocol had a higher risk of infections (infections with protocol: six of 995 [0.6%]; infections in control: 46 of 2846 [1.62%]; relative risk: 2.68 [95% confidence interval {CI}, 1.15-0.26]; p = 0.0226). When stratified based on risk category, no differences were detected; preadmission chlorhexidine preparation was not associated with reduced infection risk for low, medium, and high NHSN risk categories (p = 0.386, 0.153, and 0.196, respectively). CONCLUSIONS: The results of our study suggest that this cloth application appears to reduce the risk of infection in patients undergoing THA. When stratified by risk categories, we found no difference in the infection rate, but these findings were underpowered. Although future multicenter randomized trials will need to confirm these preliminary findings, the intervention is inexpensive and is unlikely to be risky and so might be considered on the basis of this retrospective, comparative study. LEVEL OF EVIDENCE: Level III, therapeutic study. PMID- 26891901 TI - Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum. AB - There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-beta2 (TGF-beta2), alpha defensin 5 (HD5), beta defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-gamma, TNF-alpha and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-beta2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk. PMID- 26891899 TI - Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis. AB - Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (-) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (-) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (-) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers. PMID- 26891903 TI - Unfolding the physics of URu2Si2 through silicon to phosphorus substitution. AB - The heavy fermion intermetallic compound URu2Si2 exhibits a hidden-order phase below the temperature of 17.5 K, which supports both anomalous metallic behavior and unconventional superconductivity. While these individual phenomena have been investigated in detail, it remains unclear how they are related to each other and to what extent uranium f-electron valence fluctuations influence each one. Here we use ligand site substituted URu2Si(2-x)P(x) to establish their evolution under electronic tuning. We find that while hidden order is monotonically suppressed and destroyed for x<=0.035, the superconducting strength evolves non monotonically with a maximum near x~0.01 and that superconductivity is destroyed near x~0.028. This behavior reveals that hidden order depends strongly on tuning outside of the U f-electron shells. It also suggests that while hidden order provides an environment for superconductivity and anomalous metallic behavior, it's fluctuations may not be solely responsible for their progression. PMID- 26891904 TI - "I was so worried about every drop of milk" - feeding problems at home are a significant concern for parents after major heart surgery in infancy. AB - Increasing numbers of operations in small infants with complex congenital heart disease are being carried out in the UK year on year, with more surviving the initial operation. However, even after successful surgery some of these infants remain fragile when they are discharged home. The aim of the study was to elicit parents' experiences of caring for a child with complex needs after major congenital heart surgery. We conducted a qualitative study involving semi structured interviews with parents of 20 children (aged <1-5 months at hospital discharge), who had undergone open heart surgery and subsequently died or been readmitted unexpectedly to intensive care following their initial discharge home. Feeding difficulties following discharge from the specialist surgical centre emerged as one of the most significant parental concerns spontaneously raised in interviews. For some parents the impact of feeding difficulties overshadowed any other cardiac concerns. Key themes centred around feeding management (particularly the practical challenges of feeding their baby), the emotional impact of feeding for parents and the support parents received or needed after discharge with respect to feeding. Caring for a child with congenital heart disease following surgery is demanding, with feeding difficulties being one of the most significant parent stressors. Local health professionals can be a good source of support for parents provided that they are well informed about the needs of a cardiac baby and have realistic expectations of weight gain. Specialist surgical centres should consider addressing issues of parental stress around feeding and weight gain prior to hospital discharge. (c) 2016 Blackwell Publishing Ltd. PMID- 26891900 TI - Amino acid recognition for automatic resonance assignment of intrinsically disordered proteins. AB - Resonance assignment is a prerequisite for almost any NMR-based study of proteins. It can be very challenging in some cases, however, due to the nature of the protein under investigation. This is the case with intrinsically disordered proteins, for example, whose NMR spectra suffer from low chemical shifts dispersion and generally low resolution. For these systems, sequence specific assignment is highly time-consuming, so the prospect of using automatic strategies for their assignment is very attractive. In this article we present a new version of the automatic assignment program TSAR dedicated to intrinsically disordered proteins. In particular, we demonstrate how the automatic procedure can be improved by incorporating methods for amino acid recognition and information on chemical shifts in selected amino acids. The approach was tested in silico on 16 disordered proteins and experimentally on alpha-synuclein, with remarkably good results. PMID- 26891905 TI - Stopping antidepressants following depression. PMID- 26891902 TI - Preventive obesity agent montmorillonite adsorbs dietary lipids and enhances lipid excretion from the digestive tract. AB - Western diets are typically high in fat and are associated with long-term complications such as obesity and hepatic steatosis. Because of the enjoyable taste of high-fat diets (HFDs), we are interested in determining how to decrease lipid absorption and enhance lipid excretion from the digestive tract after the consumption of eating fatty foods. Montmorillonite was initially characterized as a gastrointestinal mucosal barrier protective agent for the treatment of diarrhoea. Dietary lipid adsorbent- montmorillonite (DLA-M) was isolated and purified from Xinjiang montmorillonite clay via the water extraction method. Here, we show that DLA-M has an unexpected role in preventing obesity, hyperlipidaemia and hepatic steatosis in HFD-fed rats. Interestingly, combined application of polarized light microscopy and lipid staining analyses, showed that DLA-M crystals have dietary lipid-adsorbing ability in vitro and in vivo, which enhances lipid excretion via bowel movements. In summary, our results indicate that DLA-M prevent HFD-induced obesity. This novel dietary lipid adsorbing agent can help prevent obesity and its comorbidities. PMID- 26891906 TI - Botryosphaeriaceae associated with the die-back of ornamental trees in the Western Balkans. AB - Extensive die-back and mortality of various ornamental trees and shrubs has been observed in parts of the Western Balkans region during the past decade. The disease symptoms have been typical of those caused by pathogens residing in the Botryosphaeriaceae. The aims of this study were to isolate and characterize Botryosphaeriaceae species associated with diseased ornamental trees in Serbia, Montenegro, Bosnia and Herzegovina. Isolates were initially characterized based on the DNA sequence data for the internal transcribed spacer rDNA and six major clades were identified. Representative isolates from each clade were further characterized using DNA sequence data for the translation elongation factor 1 alpha, beta-tubulin-2 and large subunit rRNA gene regions, as well as the morphology of the asexual morphs. Ten species of the Botryosphaeriaceae were identified of which eight, i.e., Dothiorella sarmentorum, Neofusicoccum parvum, Botryosphaeria dothidea, Phaeobotryon cupressi, Sphaeropsis visci, Diplodia seriata, D. sapinea and D. mutila were known taxa. The remaining two species could be identified only as Dothiorella spp. Dichomera syn-asexual morphs of D. sapinea, Dothiorella sp. 2 and B. dothidea, as well as unique morphological characters for a number of the known species are described. Based on host plants and geographic distribution, the majority of Botryosphaeriaceae species found represent new records. The results of this study contribute to our knowledge of the distribution, host associations and impacts of these fungi on trees in urban environments. PMID- 26891907 TI - Posterior dynamic stabilization in the lumbar spine - 24 months results of a prospective clinical and radiological study with an interspinous distraction device. AB - BACKGROUND: Interspinous distraction devices (IDD) are due to maintain or restore intersegmental range of motion (iROM) in a controlled fashion with the aim of stabilization the affected level dynamically. The following study is the first to present clinical and radiological data with the Wallis(r) spacer during a follow up of 24 months. METHODS: Ten patients underwent posterior dynamic stabilization (PDS) of the lumbar spine with an IDD (Wallis(r) spacer) and were controlled clinically and radiologically after 3, 6, 12, and 24 months in a prospective study design. Pain intensity, functional disability and life quality were assessed by use of subjective scores. Motion analyses were performed with the help of lateral functional x-rays to determine the iROM of the operated segments and total ROM (tROM) of the lumbar spine. In addition, roentgen stereophotogrammetric analysis (RSA) was used to measure the iROM of the treated levels. RESULTS: During the postoperative course pain and disability most clinical scores were significantly improved. After 24 months we observed statistically significant reduction in back pain intensity with a mean value of 6.0 on visual analog scale (VAS) before surgery and of 2.7 at the latest evaluation. The leg pain was also decreased without statistical significance from 4.7 preoperatively to 2.1 at final follow-up. The functional disability according to Oswestry Disability Index (ODI) and Roland-Morris Disability Questionnaire (RM) was decreased both with statistical significance at all examination dates with a mean value in ODI of 40.0 % before operation and of 17.3 % after 2 years and an initial mean value in RM of 55.2 and of 23.5 % after latest follow-up. After 24 months, the results of the health related quality of life score also showed much better values with only two exceptions. The iROM of the treated levels was reduced during each follow-up examination with preserved residual mobility. Directly postoperatively and after 3 and 12 months intersegmental mobility was statistically significantly decreased with an average iROM of 6.62 degrees before operation and of 2.69 degrees few days after surgery, of 3.79 degrees and 3.16 degrees 3 and 12 months later. At 6 (4.37 degrees ) and 24 (4.01 degrees ) months follow-up iROM was also but not statistically significantly reduced. The mean tROM did not change significantly during all postoperative controls. CONCLUSIONS: The radiological findings support the thesis of posterior dynamic stabilization by the used implant. The positive clinical findings should be interpreted with caution because of the limited number of patients and the missing control group. PMID- 26891908 TI - Design and synthesis of some new 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl piperazine1-yl)-phenyl-ureas as potent anticonvulsant and antidepressant agents. AB - A series of 1-phenyl-3/4-[4-(aryl/heteroaryl/alkyl-piperazine1-yl)-phenyl-urea derivatives (29-42) were designed, synthesized and evaluated for their anticonvulsant activity by using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) seizure tests. The acute neurotoxicity was checked by rotarod assay. Most of the test compounds were found effective in both seizure tests. Compound 30 (1-{4-[4-(4-chloro-phenyl)-piperazin-1-yl]-phenyl}-3-phenyl urea) exhibited marked anticonvulsant activity in MES as well as scPTZ tests. The phase II anticonvulsant quantification study of compound 30 indicates the ED50 value of 28.5 mg/kg against MES induced seizures. In addition, this compound also showed considerable protection against pilocarpine induced status epilepticus in rats. Seizures induced by 3-mercaptopropionic acid model and thiosemicarbazide were significantly attenuated by compound 30, which suggested its broad spectrum of anticonvulsant activity. Interestingly, compound 30 displayed better antidepressant activity than standard drug fluoxetine. Moreover, compound 30 appeared as a non-toxic chemical entity in sub-acute toxicity studies. PMID- 26891911 TI - Erratum to: 'Perioperative use of crystalloids in patients undergoing open radical cystectomy: balanced Ringer's maleate versus a glucose 5%/potassium-based balanced solution: study protocol for a randomized controlled trial'. PMID- 26891910 TI - Is serum HER2 ECD a predictive biomarker for response to trastuzumab in advanced gastric cancer? PMID- 26891909 TI - Direct evidence for activated CD8+ T cell transmigration across portal vein endothelial cells in liver graft rejection. AB - BACKGROUND: Lymphocyte recruitment into the portal tract is crucial not only for homeostatic immune surveillance but also for many liver diseases. However, the exact route of entry for lymphocytes into portal tract is still obscure. We investigated this question using a rat hepatic allograft rejection model. METHODS: A migration route was analyzed by immunohistological methods including a recently developed scanning electron microscopy method. Transmigration-associated molecules such as selectins, integrins, and chemokines and their receptors expressed by hepatic vessels and recruited T-cells were analyzed by immunohistochemistry and flow cytometry. RESULTS: The immunoelectron microscopic analysis clearly showed CD8beta(+) cells passing through the portal vein (PV) endothelia. Furthermore, the migrating pathway seemed to pass through the endothelial cell body. Local vascular cell adhesion molecule-1 (VCAM-1) expression was induced in PV endothelial cells from day 2 after liver transplantation. Although intercellular adhesion molecule-1 (ICAM-1) expression was also upregulated, it was restricted to sinusoidal endothelia. Recipient T cells in the graft perfusate were CD25(+)CD44(+)ICAM-1(+)CXCR3(+)CCR5(-) and upregulated alpha4beta1 or alphaLbeta2 integrins. Immunohistochemistry showed the expression of CXCL10 in donor MHCII(high) cells in the portal tract as well as endothelial walls of PV. CONCLUSIONS: We show for the first time direct evidence of T-cell transmigration across PV endothelial cells during hepatic allograft rejection. Interactions between VCAM-1 on endothelia and alpha4beta1 integrin on recipient effector T-cells putatively play critical roles in adhesion and transmigration through endothelia. A chemokine axis of CXCL10 and CXCR3 also may be involved. PMID- 26891912 TI - Improved delivery of poorly soluble compounds using nanoparticle technology: a review. AB - Although a large number of new drug molecules with varied therapeutic potentials have been discovered in the recent decade, yet most of them are still in developmental process. This can be attributed to the limited aqueous solubility which governs the bioavailability of such drug molecules. Hence, there is a requisite for a technology-based product (formulation) in order to overcome such issues without compromising on the therapeutic response. The purpose of this review is to provide an insight to the formulation of drug nanoparticles for enhancing solubility and dissolution velocity with concomitant enhancement in bioavailability. In the recent decade, nanonization has evolved from a concept to reality owing to its versatile applications, especially in the development of drugs having poor solubility. In this review, a relatively simple and scalable approach for the manufacture of drug nanoparticles and latest characterization techniques utilized to evaluate the drug nanoparticles are discussed. The drug nanoparticulate approach described herein provides a general applicability of the platform technology in designing a formulation for drugs associated with poor aqueous solubility. PMID- 26891913 TI - Phase I study of concurrent selective lymph node late-course accelerated hyperfractionated radiotherapy and S-1 plus cisplatin for locally advanced oesophageal squamous cell carcinoma. AB - OBJECTIVE: This Phase I study aimed to assess the safety and efficacy of concurrent selective lymph node (SLN) late-course accelerated hyperfractionated (LCAF) intensity-modulated radiotherapy (IMRT) and S-1 plus cisplatin (CDDP) for the locally advanced oesophageal squamous-cell carcinoma (ESCC). METHODS: The total dose of SLN LCAF IMRT was 59.6 Gy/34 fractions in 5.4 weeks. The concurrent chemotherapy (CCRT) was administered as follows: CDDP 25 mg m(-2) on Days 1-3 and Days 22-24; S-1 was applied in a de-escalating dosage with a decrement of 10 mg m(-2) per day, from its full dose level of 80 mg m(-2), orally twice daily on Days 1-14 and Days 22-35. We inferred the maximum-tolerated dose (MTD), dose limiting toxicities (DLTs) and recommended dose, according to adverse reaction during CCRT. RESULTS: Totally, 15 patients with ESCC with T2-4N0-1M0-1a were enrolled in Dose Level 1 (80 mg m(-2)). In the initial five patients, two patients developed DLTs. As MTD was not reached, five additional patients were treated with the same dose level, and DLTs occurred in only one patient. Similar results were found in the last five patients. After CCRT, the objective response rates were 100% for primary tumours and 86.2% for metastatic lymph nodes, respectively. Totally, the observed Grade 3 toxicities during CCRT were leukopenia (20%), neutropenia (20%) and dermatitis (13.3%), and no Grade 4 toxicity occurred. The Kaplan-Meier-estimated overall and progression survival rates were 86.7% and 66.7% (1 year), 73.3% and 60% (2 years) and 73.3% and 60% (3 years). CONCLUSION: The concurrent SLN LCAF IMRT and chemotherapy with S-1 and CDDP was well tolerated and showed promising efficacy. The dose of S-1 in this regimen was recommended with 80 mg m(-2) orally twice daily on Days 1-14 and Days 22-35. ADVANCES IN KNOWLEDGE: CCRT with S-1 plus CDDP exhibited encouraging results with milder toxicities, high objective response rates and ideal overall survival time. PMID- 26891914 TI - Resveratrol augments ER stress and the cytotoxic effects of glycolytic inhibition in neuroblastoma by downregulating Akt in a mechanism independent of SIRT1. AB - Cancer cells typically display increased rates of aerobic glycolysis that are correlated with tumor aggressiveness and a poor prognosis. Targeting the glycolytic pathway has emerged as an attractive therapeutic route mainly because it should spare normal cells. Here, we evaluate the effects of combining the inhibition of glycolysis with application of the polyphenolic compound resveratrol (RSV) in neuroblastoma (NB) cancer cell lines. Inhibiting glycolysis with 2-deoxy-D-glucose (2-DG) significantly reduced NB cell viability and was associated with increased endoplasmic reticulum (ER) stress and Akt activity. Administration of 2-DG increased the expression of the ER molecular chaperones GRP78 and GRP94, the prodeath protein C/EBP homology protein (CHOP) and the phosphorylation of Akt at S473, T450 and T308. Combined treatment with both RSV and 2-DG reduced GRP78, GRP94 and Akt phosphorylation but increased CHOP and NB cell death when compared with the administration of 2-DG alone. The selective inhibition of Akt activity also decreased 2-DG-induced GRP78 and GRP94 expression and increased CHOP expression, suggesting that Akt can modulate ER stress. Protein phosphatase 1alpha (PP1alpha) was activated by RSV, as indicated by a reduction in PP1alpha phosphorylation at T320. Pretreatment of cells with tautomycin, a selective PP1alpha inhibitor, prevented the RSV-mediated decrease in Akt phosphorylation, suggesting that RSV enhances 2-DG-induced cell death by activating PP1 and downregulating Akt. The RSV-mediated inhibition of Akt in the presence of 2-DG was not prevented by the selective inhibition of SIRT1, a known target of RSV, indicating that the effects of RSV on this pathway are independent of SIRT1. We propose that RSV inhibits Akt activity by increasing PP1alpha activity, thereby potentiating 2-DG-induced ER stress and NB cell death. PMID- 26891916 TI - Proteomics of edible mushrooms: A mini-review. AB - Mushrooms are considered an important food for their traditionally famous nutritional and medicinal values, although much information about their potential at the molecular level is unfortunately unknown. Edible mushrooms include fungi that are either collected wild or cultivated. Many important species are difficult to cultivate but attempts have been made with varying degrees of success, with the results showing unsatisfactory economical cultivation methods. Recently, proteomic analysis has been developed as a powerful tool to study the protein content of fungi, particularly basidiomycetes. This mini-review article highlights the contribution of proteomics platforms to the study of edible mushrooms, focusing on the molecular mechanisms involved in developmental stages. This includes extracellular and cytoplasmic effector proteins that have potential or are involved in the synthesis of anticancer, antidiabetic, antioxidant, and antibiotic, in blood pressure control, in the supply of vitamins and minerals, and in other responses to environmental changes. The contribution of different proteomics techniques including classical and more advanced techniques is also highlighted. PMID- 26891915 TI - The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review. AB - BACKGROUND: Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. METHODS: A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil. RESULTS: The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy. CONCLUSION: These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness. STUDY REGISTRATION: CRD42015023756 (PROSPERO). PMID- 26891918 TI - Note to readers. PMID- 26891917 TI - Multi-stability of circadian phase wave within early postnatal suprachiasmatic nucleus. AB - The suprachiasmatic nucleus (SCN) is a group of cells that functions as a biological master clock. In different SCN cells, oscillations of biochemical markers such as the expression-level of clock genes, are not synchronized but instead form slow circadian phase waves propagating over the whole cell population spatio-temporal structure is a fixed property set by the anatomy of a given SCN. Here, we show that this is not the case in early postnatal SCN. Earlier studies presumed that their Based on bioluminescence imaging experiments with Per2-Luciferase mice SCN cultures which guided computer simulations of a realistic model of the SCN, we demonstrate that the wave is not unique but can be in various modes including phase- coherent oscillation, crescent-shaped wave, and most notably, a rotating pinwheel wave that conceptually resembles a wall clock with a rotating hand. Furthermore, mode transitions can be induced by a pulse of 38.5 degrees C temperature perturbation. Importantly, the waves support a significantly different period, suggesting that neither a spatially-fixed phase ordering nor a specialized pacemaker having a fixed period exist in these studied SCNs. These results lead to new important questions of what the observed multi stability means for the proper function of an SCN and its arrhythmia. PMID- 26891919 TI - Estimating finite-population reproductive numbers in heterogeneous populations. AB - The basic reproductive number, R0, is one of the most important epidemiological quantities. R0 provides a threshold for elimination and determines when a disease can spread or when a disease will die out. Classically, R0 is calculated assuming an infinite population of identical hosts. Previous work has shown that heterogeneity in the host mixing rate increases R0 in an infinite population. However, it has been suggested that in a finite population, heterogeneity in the mixing rate may actually decrease the finite-population reproductive numbers. Here, we outline a framework for discussing different types of heterogeneity in disease parameters, and how these affect disease spread and control. We calculate "finite-population reproductive numbers" with different types of heterogeneity, and show that in a finite population, heterogeneity has complicated effects on the reproductive number. We find that simple heterogeneity decreases the finite population reproductive number, whereas heterogeneity in the intrinsic mixing rate (which affects both infectiousness and susceptibility) increases the finite population reproductive number when R0 is small relative to the size of the population and decreases the finite-population reproductive number when R0 is large relative to the size of the population. Although heterogeneity has complicated effects on the finite-population reproductive numbers, its implications for control are straightforward: when R0 is large relative to the size of the population, heterogeneity decreases the finite-population reproductive numbers, making disease control or elimination easier than predicted by R0. PMID- 26891920 TI - A Microstructured Fiber with Defined Borosilicate Regions to Produce a Radial Micronozzle Array for Nanoelectrospray Ionization. AB - This work highlights the possibility of using microstructured fibres with predefined doped regions to produce functional microstructures at a fibre facet with differential chemical etching. A specially designed silica microstructured fibre (MSF) that possesses specific boron-doped silica regions was fabricated for the purpose of generating a radial micronozzle array. The MSF was drawn from a preform comprising pure silica capillaries surrounded by boron-doped silica rods. Different etching rates of the boron-doped and silica regions at the fiber facet produces raised nozzles where the silica capillaries were placed. Fabrication parameters were explored in relation to the fidelity and protrusion length of the nozzle. Using etching alone, the nozzle protrusion length was limited, and the inner diameter of the channels in the array is expanded. However with the addition of a protective water counter flow, nozzle protrusion is increased to 60 MUm with a limited increase in hole diameter. The radial micronozzle array generated nine individual electrosprays which were characterized using spray current measurements and related to theoretical prediction. Signal enhancement for the higher charge state ions for two peptides showed a substantial signal enhancement compared to conventional emitter technology. PMID- 26891921 TI - Return to the operating room following decompression surgery-infection or not infection? That is the question. AB - COMMENTARY ON: Yang S, Werner BC, Cancienne JM, Hassanzadeh H, Shimer AL, Shen FH, Singla A. Preoperative epidural injections are associated with increased risk of infection after single-level lumbar decompression. Spine J 2016:16:190-5 (in this issue). PMID- 26891922 TI - Commentary on the primary stability of three different iliosacral screw fixation techniques in osteoporotic cadaver specimens-a biomechanical investigation. AB - COMMENTARY ON: Oberkircher L, Masaeli A, Bliemel C, Debus F, Ruchholtz S, Kruger A. Primary stability of three different iliosacral screw fixation techniques in osteoporotic cadaver specimens-a biomechanical investigation. Spine J 2016:16:225 31 (in this issue). PMID- 26891923 TI - Reoperation rate and risk factors of elective spinal surgery for degenerative spondylolisthesis: still more challenges lie ahead. PMID- 26891924 TI - Reply to "Reoperation rate and risk factors of elective spinal surgery for degenerative spondylolisthesis: still more challenges lie ahead". PMID- 26891926 TI - Biotransformation of Microcystins in Eukaryotic Cells - Possible Future Research Directions. AB - Due to eutrophication processes in our water bodies, cyanobacterial blooms can develop worldwide. Most of these blooms are toxic. The most prominent cyanobacterial toxins are the group of the microcystins, which are cyclic heptapeptides, currently with more than 100 congeners known. The biotransformation of microcystins starts with the conjugation to the cell internal tripeptide glutathione, catalysed by glutathione S-transferase enzymes. This conjugate is further broken down to a cysteine conjugate, enhancing the cell internal transport and excretion of the conjugated toxin from the organisms. Still many questions remain open, thinking on an obviously good working detoxification system on the one side and the often seen negative effects up to the death of humans on the other sides. PMID- 26891927 TI - The Effects of Microcystins (Cyanobacterial Heptapeptides) on the Eukaryotic Cytoskeletal System. AB - Microcystins (MCYs) are cyanobacterial heptapeptides known for their high toxicity in eukaryotic cells and for their potential human health hazards. They are potent and specific inhibitors of type 1 and 2A, serine-threonine protein phosphatases (PP1 and PP2A) and as such, interfere with key cellular and metabolic events. Moreover, they induce oxidative stress involving reactive oxygen species (ROS) generation. Their cytoskeletal effects involve both mitotic and differentiated eukaryotic cells. The main objective of the present review is to summarize the most important cytoskeletal effects of MCY on human, animal and plant cells known to date and to give an insight into the cellular and molecular background of these alterations. Disruptions of microtubule (MTs), microfilament (MF) and intermediate filament (IF) organization have all been described, having consequences on cell shape, tissue integrity and functionality and mitotic division. Most of these subcellular changes are closely related to PP1 and PP2A inhibition and involve misfunctioning of cytoskeleton associated proteins. However, several cytoskeletal alterations are likely to be related to the induction of oxidative stress. MCY induced changes in MT, MF and IF assembly may have severe human health consequences. The main target of cyanotoxin in human/ animal cells is liver and cytoskeletal disruption alters structure and functioning of hepatocytes. However, many other cell types undergo alterations similar to those observed in hepatocytes. Both PP1/PP2A inhibition and ROS generation are involved and the activation of mitogen activated protein kinases (MAPKs) seems to play a crucial role in the molecular events leading to cytoskeletal disruption. PMID- 26891928 TI - New Insights on the Mode of Action of Microcystins in Animal Cells - A Review. AB - Microcystins (MCs) are the most commonly occurring hepatotoxins produced by cyanobacteria. The inhibition of PP2A is widely assumed as the principal mechanism of toxicity of MCs, however recently it has been found that MC modulates PP2A activity not only by direct inhibition of its activity, but also by regulating its expression. Nevertheless the mechanisms of toxicity of MCs seem to be more complex to interpret than expected. The induction of some cellularmolecular mechanisms appears to be biphasic in time and concentration of MC and in most cases related with the intracellular ROS generation. These intracellular ROS levels cause oxidative stress which leads to changes in several markers of MC-LR-induced oxidative stress ultimately resulting in apoptosis or cell damage and also genotoxicity. MCs can also induce severe changes in the cytoskeleton elements: microfilaments, intermediate filaments and microtubules, which results in changes in the cytoskeleton architecture and cell viability. There are also indications that there are second messengers involved in MC-LR mediated cytotoxicity and apoptosis. Different congeners of these toxins induce different degrees of responses in the cell, assumed to be related with the capacity of toxin internalization, affinity towards PP1 and PP2A, and the ability to cause oxidative stress. MCs have also been implicated in neurotoxicity and in damages in reproductive organs. The regulation of transcription factors and proto oncogenes by MC is the mode of action of MCs tumor promotion. This review summarizes mainly the findings from the last five years about the molecular mechanisms behind MC toxicity in animal cells. PMID- 26891929 TI - Mechanisms of Microcystin-induced Cytotoxicity and Apoptosis. AB - In recent years, cyanobacterial blooms have dramatically increased and become an ecological disaster worldwide. Cyanobacteria are also known to produce a wide variety of toxic secondary metabolites, i.e. cyanotoxins. Microcystins (MCs), a group of cyclic heptapeptides, are considered to be one of the most common and dangerous cyanobacterial toxins. MCs can be incorporated into the cells via organic anion transporting polypeptides (Oatps). It's widely accepted that inhibition of protein phosphatases (PPs) and induction of oxidative stress are the main toxic mechanisms of MCs. MCs are able to induce a variety of toxic cellular effects, including DNA damage, cytoskeleton disruption, mitochondria dysfunction, endoplasmic reticulum (ER) disturbance and cell cycle deregulation, all of which can contribute to apoptosis/programmed cell death. This review aimed to summarize the increasing data regarding the intracellular biochemical and molecular mechanisms of MC-induced toxicity and cell death. PMID- 26891931 TI - Nanoemulsion: A Novel Eon in Cancer Chemotherapy. AB - Cancer refers to an assemblage of lethal diseases characterized by abnormal growth of cells. The most celebrated adverse effects accredited to the cytotoxic class of anticancer agents are constructed owing to their inability to differentiate between the abnormally multiplying cancerous cell mass and the rapidly dividing healthy cells of the human body. Consequently, unknown targets chemotherapy for cancer play host to a multitude of adverse effects ranging from nausea, alopecia to torturous ages associated with the current treatment etiquette. Nano-pharmaceuticals constitute the advanced scale drug targeting technologies. Nanoemulsion is an important tool in the nano-technological arena designed for clinical and therapeutic application. Currently among different nano carriers, nanoemulsions are extensively envisaged as efficient drug delivery systems for the targeted delivery of lipophilic cytotoxic antineoplastic agents. Beauties of nanoemulsion include optical clarity, biocompatibility, non immunogenic, biodegradable, drug encapsulation, sustained and controlled release, nanometric size, large surface area, ease of preparation and thermodynamic stability. After excessive delving, the research fraternity has acknowledged nanoemulsions as proficient nanocarriers capable of effectively addressing the low bioavailability and noncompliance issues associated with the conventional anticancerous chemotherapeutic dosage forms. This review attempts to shed new light on the current status of nanoemulsion in the cancer therapeutics, and commercial field on the basis of morphology, formulation, characteristics and characterization parameters. PMID- 26891930 TI - Nanomedicine to Deal With Cancer Cell Biology in Multi-Drug Resistance. AB - Today Cancer still remains a major cause of mortality and death worldwide, in humans. Chemotherapy, a key treatment strategy in cancer, has significant hurdles such as the occurrence of chemoresistance in cancer, which is inherent unresponsiveness or acquired upon exposure to chemotherapeutics. The resistance of cancer cells to an antineoplastic agent accompanied to other chemotherapeutic drugs with different structures and mechanisms of action called multi-drug resistance (MDR) plays an important role in the failure of chemo- therapeutics. MDR is primarily based on the overexpression of drug efflux pumps in the cellular membrane, which belongs to the ATP-binding cassette (ABC) superfamily of proteins, are P-gp (P-glycoprotein) and multidrug resistance-associated protein (MRP). Over the years, various strategies have been evaluated to overcome MDR, based not only on the use of MDR modulators but also on the implementation an innovative approach and advanced nanosized drug delivery systems. Nanomedicine is an emerging tool of chemotherapy that focuses on alternative drug delivery for improvement of the treatment efficacy and reducing side effects to normal tissues. This review aims to focus on the details biology, reversal strategies option with the limitation of MDR and various advantages of the present medical science nanotechnology with intracellular delivery aspects for overcoming the significant potential for improving the treatment of MDR malignancies. PMID- 26891932 TI - Theranostic Nanomedicine; A Next Generation Platform for Cancer Diagnosis and Therapy. AB - In the recent years, theranostic nanomedicine based strategies have gained much attention in the field of oncology particularly, in the development of new generation cancer diagnostic and therapeutic tools. Today, various approaches have been developed for bioactive(s) targeting to predefined pathological sites, as well as for quantification of physiological processes and visualization. Significant attempts have been made to combine therapeutic and diagnostic properties in to a single effective nanomedicine formulation. This concept, coined as "theranostics" is smart nanosystem(s), able to diagnose, bioactive(s) delivery and monitoring of therapeutic response. By combining therapeutic functionalities with molecular imaging, theranostic based strategies may be beneficial in the selection of therapy, planning of treatment, monitoring of objective response and planning of follow-up therapy based on the specific molecular characteristics of a disease. In this manuscript, we reviewed the recent development of theranostic approaches, various nanosystems as theranostic agents and applications of theranostic in cancer therapeutics and diagnostics. PMID- 26891933 TI - Experimental Models for Evaluation of Nanoparticles in Cancer Therapy. AB - Nanoparticles (NPs), the submicron-sized colloidal particles, have recently generated enormous interest among biomedical scientists, particularly in cancer therapy. A number of models are being used for exploring NPs safety and efficacy. Recently, cancer cell lines have explored as prominent experimental models for evaluating pharmacokinetic parameters, cell viability, cytotoxicity and drug efficacy in tumor cells. This review aims at thorough compilation of various cancer cell lines and in vivo models for evaluation of efficacy of NPs on one platform. This will provide a basis to explore and improvise pre-clinical models as a prelude to successful cancer research. PMID- 26891934 TI - Significance of Various Experimental Models and Assay Techniques in Cancer Diagnosis. AB - The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer. PMID- 26891935 TI - Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection. AB - Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized. PMID- 26891936 TI - Multimodal Nanomedicine Strategies for Targeting Cancer Cells as well as Cancer Stem Cell Signalling Mechanisms. AB - Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed. PMID- 26891938 TI - Activation of Organic Photovoltaic Light Detectors Using Bend Leakage from Optical Fibers. AB - This work investigates the detection and subsequent utilization of leaked light from bends in a silica optical fiber using organic photovoltaic detectors. The optic power lost by single mode and multimode silica optical fibers was calibrated for bend radii between 1 and 7 mm for 532 and 633 nm light, exhibiting excellent agreement with previous theoretical solutions. The spatial location of maximum power leakage on the exterior of the fiber was found to exist in the same plane as the fiber, with a 10 degrees offset from the normal. Two different organic photovoltaic detectors fabricated using a poly(3-hexylthiophene):indene C60-bisadduct donor-acceptor blend cast from chloroform and chlorobenzene were fabricated to detect the leaked light. The two detectors exhibited different photovoltaic performances, predominantly due to different active layer thicknesses. Both devices showed sensitivity to leakage light, exhibiting voltages between 200 and 300 mV in response to leaked light from the fiber. The temporal responses of the devices were observed to differ, with a rise time from 10% to 90% of maximum voltage of 1430 MUs for the chlorobenzene device, and a corresponding rise time of 490 MUs for the higher performing chloroform device. The two OPVs were used to simultaneously detect leaked light from induced bends in the optical fiber, with the differing temporal profiles employed to create a unique time-correlated detection signal with enhanced security. The delay between detection of each OPV voltage could be systematically varied, allowing for either a programmable and secure single detection signal or triggering of multiple events with variable time resolution. The results reported in this study present exciting avenues toward the deployment of this simple and noninvasive optical detection system in a range of different applications. PMID- 26891937 TI - Peripheral activities of growth hormone-releasing hormone. AB - Growth hormone (GH)-releasing hormone (GHRH) is produced by the hypothalamus and stimulates GH synthesis and release in the anterior pituitary gland. In addition to its endocrine role, GHRH exerts a wide range of extrapituitary effects which include stimulation of cell proliferation, survival and differentiation, and inhibition of apoptosis. Accordingly, expression of GHRH, as well as the receptor GHRH-R and its splice variants, has been demonstrated in different peripheral tissues and cell types. Among the direct peripheral activities, GHRH regulates pancreatic islet and beta-cell survival and function and endometrial cell proliferation, promotes cardioprotection and wound healing, influences the immune and reproductive systems, reduces inflammation, indirectly increases lifespan and adiposity and acts on skeletal muscle cells to inhibit cell death and atrophy. Therefore, it is becoming increasingly clear that GHRH exerts important extrapituitary functions, suggesting potential therapeutic use of the peptide and its analogs in a wide range of medical settings. PMID- 26891940 TI - Antifungal activity of Rubus chingii extract combined with fluconazole against fluconazole-resistant Candida albicans. AB - This study aimed to investigate the antifungal activity of Rubus chingii extract in combination with fluconazole (FLC) against FLC-resistant Candida albicans 100 in vitro. A R. chingii extract and FLC-resistant C. albicans fungus suspension were prepared. The minimum inhibitory concentration and fractional inhibitory concentration index of R. chingii extract combined with FLC against C. albicans were determined, after which growth curves for C. albicans treated with R. chingii extract, FLC alone and a combination of these preparations were constructed. Additionally, the mechanisms of drug combination against C. albicans were explored by flow cytometry, gas chromatographic mass spectrometry and drug efflux pump function detection. R. chingii extract combined with FLC showed significant synergy. Flow cytometry suggested that C. albicans cells mainly arrest in G1 and S phases when they have been treated with the drug combination. The drug combination resulted in a marked decrease in the ergosterol content of the cell membrane. Additionally, efflux of Rhodamine 6G decreased with increasing concentrations of R. chingii extract. R. chingii extract combined with FLC has antifungal activity against FLC-resistant C. albicans. PMID- 26891939 TI - Inorganic arsenic and respiratory health, from early life exposure to sex specific effects: A systematic review. AB - This systematic review synthesizes the diverse body of epidemiologic research accrued on inorganic arsenic exposure and respiratory health effects. Twenty-nine articles were identified that examined the relationship between inorganic arsenic exposure and respiratory outcomes (i.e. lung function, symptoms, acute respiratory infections, chronic non-malignant lung diseases, and non-malignant lung disease mortality). There was strong evidence of a general association between arsenic and non-malignant respiratory illness, including consistent evidence on lung function impairment, acute respiratory tract infections, respiratory symptoms, and non-malignant lung disease mortality. Overall, early life exposure (i.e. in utero and/or early-childhood) had a marked effect throughout the lifespan. This review also identified some research gaps, including limited evidence at lower levels of exposure (water arsenic <100MUg/L), mixed evidence of sex differences, and some uncertainty on arsenic and any single non-malignant respiratory disease or pathological process. Common limitations, including potential publication bias; non-comparability of outcome measures across included articles; incomplete exposure histories; and limited confounder control attenuated the cumulative strength of the evidence as it relates to US populations. This systematic review provides a comprehensive assessment of the epidemiologic evidence and should be used to guide future research on arsenic's detrimental effects on respiratory health. PMID- 26891941 TI - Association of TRPM3 Polymorphism (rs10780946) and Aspirin-Exacerbated Respiratory Disease (AERD). AB - INTRODUCTION: Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma rhinosinusitis and poliposis; ingestion of aspirin or other non-steroid anti-inflammatory drugs exacerbate asthma-like symptoms. The pathogenesis of AERD is unknown, and genetic and environmental factors contribute to the disease. Our objective is identifying polymorphisms associated with susceptibility in a Mexican mestizo population. METHODS: Primarily we performed custom Illumina goldengate array-based genotyping of 1512 SNPs, carefully selected from a variety of acute/chronic inflammatory lung conditions previously reported. Four SNPs in TRPM3 gene showed the lowest p-values (rs10780946, rs7025694, rs1889915, and rs7047645). We further selected rs10780946 and rs7025694 for validation using Taqman genotyping (n = 743; 288 AERD, 272 ATA, and 183 HC). RESULTS: rs10780946 showed association when compared between AERD and ATA groups under co-dominant (p = 0.006), dominant (p = 0.002), overdominant (p = 0.01), and log-additive (p = 0.03) genetic models. AERD showed increased heterozygous TC (rs10780946-rs7025694) haplotype compared to ATA and HC (p < 0.05). We could not confirm any association between rs7025694 and AERD. CONCLUSION: rs10780946 TRPM3 polymorphism is associated with AERD susceptibility. PMID- 26891943 TI - Protection or Vulnerability? A Meta-Analysis of the Relations Between the Positive and Negative Components of Self-Compassion and Psychopathology. AB - Self-compassion is increasingly explored as a protective factor in relation to psychopathology. The Self-Compassion Scale (SCS) and its Short Form variant (SCS SF) are the most widely used instruments for measuring this psychological construct, and previous studies have indeed shown that the total score of this scale is negatively associated with psychopathology. In this article, we point out that half of the items of the SCS and SCS-SF are positive indicators of self compassion and directly refer to the three key components of self-kindness, common humanity and mindfulness, while the other half of the items are negative indicators of the construct and reflect the precise opposite of the key components, namely self-judgment, isolation and over-identification. A meta analysis was conducted including 18 studies that reported on the positive and negative indicators of self-compassion as indexed by the SCS/SCS-SF and their relations to various types of psychopathology. Results showed that positive indicators of self-compassion were negatively associated with psychopathology, which confirms their hypothesized protective influence. However, the negative indicators were positively linked to psychopathology, suggesting that these scales tap increased vulnerability to mental health problems. Moreover, tests comparing the strength of the relations between various SCS/SCS-SF counterparts (i.e., self-kindness versus self-judgment, common humanity versus isolation and mindfulness versus over-identification) and psychopathology showed that the negative indicators were significantly stronger linked to mental health problems than the positive indicators. This provides support for the idea that the use of a total self-compassion score of the SCS or SCS-SF, which typically includes the reversely scored negative subscales, will probably result in an inflated relationship with symptoms of psychopathology. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26891942 TI - Modelling semi-attributable toxicity in dual-agent phase I trials with non concurrent drug administration. AB - In oncology, combinations of drugs are often used to improve treatment efficacy and/or reduce harmful side effects. Dual-agent phase I clinical trials assess drug safety and aim to discover a maximum tolerated dose combination via dose escalation; cohorts of patients are given set doses of both drugs and monitored to see if toxic reactions occur. Dose-escalation decisions for subsequent cohorts are based on the number and severity of observed toxic reactions, and an escalation rule. In a combination trial, drugs may be administered concurrently or non-concurrently over a treatment cycle. For two drugs given non-concurrently with overlapping toxicities, toxicities occurring after administration of the first drug yet before administration of the second may be attributed directly to the first drug, whereas toxicities occurring after both drugs have been given some present ambiguity; toxicities may be attributable to the first drug only, the second drug only or the synergistic combination of both. We call this mixture of attributable and non-attributable toxicity semi-attributable toxicity. Most published methods assume drugs are given concurrently, which may not be reflective of trials with non-concurrent drug administration. We incorporate semi attributable toxicity into Bayesian modelling for dual-agent phase I trials with non-concurrent drug administration and compare the operating characteristics to an approach where this detail is not considered. Simulations based on a trial for non-concurrent administration of intravesical Cabazitaxel and Cisplatin in early stage bladder cancer patients are presented for several scenarios and show that including semi-attributable toxicity data reduces the number of patients given overly toxic combinations. (c) 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID- 26891945 TI - Corrigendum. PMID- 26891944 TI - Clinical implications of omics and systems medicine: focus on predictive and individualized treatment. AB - Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples. PMID- 26891946 TI - Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. AB - Brivaracetam is the latest approved antiepileptic drug in focal epilepsy and exhibits high affinity as SV2A-ligand. More than two thousand patients have received brivaracetam within randomized placebo-controlled trials. Significant median seizure reduction rates of 30.5% to 53.1% for 50 mg/d, 32.5% to 37.2% for 100 mg/d and 35.6% for 200 mg/d were reported. Likewise, 50% responder rates were 32.7% to 55.8% for 50 mg/d, 36% to 38.9% for 100 mg/d and 37.8% for 200 mg/d. Overall, brivaracetam is well tolerated. The main adverse events are fatigue, dizziness, and somnolence. Immediate switch from levetiracetam to brivaracetam at a conversion ratio between 10:1 to 15:1 is feasible, and might alleviate the behavioral side effects associated with levetiracetam. Brivaracetam has the potential to perform as an important, possibly broad-spectrum AED, initially in patients with drug-refractory epilepsies. Its intravenous formulation may be a new and desirable alternative for status epilepticus, but there is so far no experience in these patients. PMID- 26891947 TI - Introduction: Engaging researchers on developing, using, and improving knowledge synthesis methods: a series of articles describing the results of a scoping review on emerging knowledge synthesis methods. PMID- 26891948 TI - Knowledge synthesis methods for integrating qualitative and quantitative data: a scoping review reveals poor operationalization of the methodological steps. AB - OBJECTIVES: To describe and compare, through a scoping review, emerging knowledge synthesis methods for integrating qualitative and quantitative evidence in health care, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. STUDY DESIGN AND SETTING: Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. RESULTS: In total, 121 articles reporting seven knowledge synthesis methods (critical interpretive synthesis, integrative review, meta-narrative review, meta summary, mixed studies review, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Common similarities among methods related to the entire synthesis process, while common differences related to the research question and eligibility criteria. The most common strength was a comprehensive synthesis providing rich contextual data, whereas the most common weakness was a highly subjective method that was not reproducible. For critical interpretive synthesis, meta-narrative review, meta summary, and narrative synthesis, guidance was not provided for some steps of the review process. CONCLUSION: Some of the knowledge synthesis methods provided guidance on all steps, whereas other methods were missing guidance on the synthesis process. Further work is needed to clarify these emerging knowledge synthesis methods. PMID- 26891949 TI - A scoping review identifies multiple emerging knowledge synthesis methods, but few studies operationalize the method. AB - OBJECTIVES: To systematically identify, define, and classify emerging knowledge synthesis methods through a scoping review. STUDY DESIGN AND SETTING: MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Methodology Register, the Cochrane Database of Systematic Reviews, Social Sciences Abstracts, Library and Information Science Abstracts, Philosopher's Index, and Education Resources Information Center were searched to identify articles reporting emerging knowledge synthesis methods across the disciplines of health, education, sociology, and philosophy. Two reviewers independently selected studies and abstracted data for each article. RESULTS: In total, 409 articles reporting on 25 knowledge synthesis methods were included after screening of 17,962 titles and abstracts and 1,010 potentially relevant full-text articles. Most of the included articles were an application of the method (83.9%); only 3.7% were seminal articles that fully described the method (i.e., operationalized the steps). Most of the included articles were published after 2005. The methods were most commonly used across the fields of nursing, health care science and services, and health policy. CONCLUSION: We found a lack of guidance on how to select a knowledge synthesis method. We propose convening an international group of leaders in the knowledge synthesis field to help clarify emerging approaches to knowledge synthesis. PMID- 26891950 TI - Diverse criteria and methods are used to compare treatment effect estimates: a scoping review. AB - OBJECTIVES: To determine what criteria researchers use to assess whether the estimates of effect of an intervention on a dichotomous outcome are different when obtained using different study designs. STUDY DESIGN AND SETTING: Scoping review of the literature. We included studies of dichotomous outcomes in which authors compared the estimates of effects from different study designs. We performed searches in electronic databases and in the list of references of relevant studies. Two reviewers independently selected studies and abstracted data. We created a list of the criteria used to compare estimates of effects between study designs, described their main features, and classified them using a clinical perspective. RESULTS: We included 26 studies, from which we identified 24 criteria. Most of the studies focused on comparing estimates from observational studies and randomized controlled trials (n = 19). The most common criteria aimed to determine whether there was a difference or not (n = 18), provided guidance for such a judgment (n = 16), and were based on the point estimates (n = 11). We judged 14 criteria to be appropriate and classified them as either statistically related or clinically related. CONCLUSION: We found that diverse criteria are used to compare effect estimates between study designs. Familiarity with these would aid in the interpretation of results from different studies regarding the same question. PMID- 26891951 TI - Knowledge synthesis methods for generating or refining theory: a scoping review reveals that little guidance is available. AB - OBJECTIVES: To describe and compare, through a scoping review, emerging knowledge synthesis methods for generating and refining theory, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. STUDY DESIGN AND SETTING: Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. RESULTS: In total, 287 articles reporting nine knowledge synthesis methods (concept synthesis, critical interpretive synthesis, integrative review, meta-ethnography, meta interpretation, meta-study, meta-synthesis, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Strengths of the methods included comprehensive synthesis providing rich contextual data and suitability for identifying gaps in the literature, informing policy, aiding in clinical decisions, addressing complex research questions, and synthesizing patient preferences, beliefs, and values. However, many of the methods were highly subjective and not reproducible. For integrative review, meta-ethnography, and realist review, guidance was provided on all steps of the review process, whereas meta-synthesis had guidance on the fewest number of steps. CONCLUSION: Guidance for conducting the steps was often vague and sometimes absent. Further work is needed to provide direction on operationalizing these methods. PMID- 26891952 TI - Figure analysis: A teaching technique to promote visual literacy and active Learning. AB - Learning often improves when active learning techniques are used in place of traditional lectures. For many of these techniques, however, students are expected to apply concepts that they have already grasped. A challenge, therefore, is how to incorporate active learning into the classroom of courses with heavy content, such as molecular-based biology courses. An additional challenge is that visual literacy is often overlooked in undergraduate science education. To address both of these challenges, a technique called figure analysis was developed and implemented in three different levels of undergraduate biology courses. Here, students learn content while gaining practice in interpreting visual information by discussing figures with their peers. Student groups also make connections between new and previously learned concepts on their own while in class. The instructor summarizes the material for the class only after students grapple with it in small groups. Students reported a preference for learning by figure analysis over traditional lecture, and female students in particular reported increased confidence in their analytical abilities. There is not a technology requirement for this technique; therefore, it may be utilized both in classrooms and in nontraditional spaces. Additionally, the amount of preparation required is comparable to that of a traditional lecture. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):336-344, 2016. PMID- 26891954 TI - Significant association between FasL gene -844T/C polymorphism and risk to hepatocellular carcinoma in Egyptian patients. AB - Fas/Fas ligand (FasL) system is the most critical apoptotic signaling entity in the extrinsic apoptotic pathway; hence mutations affecting this pathway may prevent the immune system from the removal of newly-formed tumor cells, and thus lead to tumor formation. The present study investigated the association between the FasL -844T/C polymorphism and the risk of hepatocellular carcinoma (HCC) in a cohort of Egyptian patients and explored the relationship of various clinical and pathological parameters with this single nucleotide polymorphism (SNP). Blood samples were withdrawn from hundred HCC patients and 100 age-, sex- and ethnically matched controls. The FasL -844T/C (rs763110) gene polymorphism was typed from genomic DNA using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Genotype distributions and allelic frequencies between patients and control subjects showed that the TT homozygous patients were two times more likely to develop HCC (p=0.011). Also, the T allele was found to be a significant risk factor for the disease (OR 1.970, 95% CI 1.250 3.105, p=0.003). No association was detected between different parameters of the disease and the SNP. For the first time, our results suggest that the -844T/C polymorphism in the FasL gene confers risk to HCC. The alarming increase in the incidence of HCC in Egypt encourages further studies to document our results in a larger sample, and recommends more genetic studies hoping to define a genomic risk prediction specific to this cancer in our population. PMID- 26891953 TI - Prognostic role of microscopically positive margins for primary gastrointestinal stromal tumors: a systematic review and meta-analysis. AB - The impact and management of microscopically positive margins in gastrointestinal stromal tumors (GISTs) remain unclear. The aim of this study is to estimate the prognostic value of surgical margins for disease-free survival (DFS) and overall survival (OS) in patients with primary GISTs. Twelve studies with 1985 GIST patients were included. The overall recurrence rate in R1 resection and R0 resection group was 0.364 (95% CI 0.299-0.429) and 0.296 (95% CI 0.161-0.430), respectively. Meta-analysis confirmed that a microscopically positive margin could significantly impact the disease-free survival (HR 1.596, 95% CI 1.128 2.258; I(2) = 37.5%, P value = 0.091), but had no influence on overall survival (HR 1.430, 95% CI 0.608-3.363; I(2) = 60.8%, P value = 0.013). Importantly, subgroup analysis revealed that adjuvant imatinib treatment could attenuate the risk of recurrence for primary GIST patients who received R1 resection. (HR 1.308, 95% CI 0.583-2.935; I(2) = 53.2%, P value = 0.074). The level of evidence achieved in this study was "moderate" for DFS and "low" for OS. In conclusion, this study revealed that a microscopically positive margin is an unfavorable prognostic factor for GIST patients with R1 resection, and adjuvant imatinib treatment is proved to be effective. PMID- 26891956 TI - Phase II study of bevacizumab plus irinotecan on the treatment of relapsed resistant small cell lung cancer. AB - PURPOSE: This phase II study investigates the efficacy and safety of DNA topoisomerase I inhibitor irinotecan plus bevacizumab a monoclonal antibody against VEGF (BEVIRI) in patients with relapsed chemo-resistant SCLC. METHODS: Patients who previously completed treatment with cisplatin-etoposide who relapsed within 3 months, had measurable extensive-stage SCLC, ECOG performance status 0-2 and adequate hematologic, renal and hepatic function, were given intravenous irinotecan 175 mg/m(2) plus intravenous bevacizumab 7.5 mg/kg on day 1 and 15 in 30 day cycles for a target of at least four cycles. No patients had received prophylactic intracranial irradiation. Treatment response was assessed with computer tomography scans with the completion of two consecutive cycles. Primary endpoint was overall response rate (ORR). RESULTS: Thirty-two patients were enrolled and 28 of them were eligible for evaluation of response, toxicity and survival. The median age was 63.5 years (range 48-73). The ORR (CR and PR) was 25 % (95 % CI 8.9-41.0) and including patients with stable disease overall disease control rate at 2 months was 89 % (95 % CI 77.41-100). The median duration of response was 6 months, median progression-free survival was 3 months (mean PFS: 3.2, 95 % CI 2.7-3.7), and median overall survival was 6 months (mean OS: 6.3, 95 % CI 5.4-7.1). The PFS rate at 6 months was 3.6 %, and 1-year OS rate was 3.6 %. The median number of cycles received was 4.5 (range 1-6). There were two (7.1 %) hematologic (neutropenia) and one (3.5 %) non-hematologic (proteinuria) serious grades 3-4 adverse reactions without necessitating treatment discontinuation. CONCLUSION: BEVIRI combination in relapsed chemo-resistant SCLC patients demonstrates promising efficacy and low toxicity compared to historical controls. Further investigation is warranted. PMID- 26891957 TI - Predictive value of repeated F-18 FDG PET/CT parameters changes during preoperative chemoradiotherapy to predict pathologic response and overall survival in locally advanced esophageal adenocarcinoma patients. AB - INTRODUCTION: The goal of the current study was to investigate the predictive and prognostic values of repeated F-18 FDG PET/CT parameter changes for prediction of complete pathologic response (pCR) in patients with adenocarcinoma of locally advanced esophageal cancer (LAEC) who received preoperative concurrent chemoradiotherapy (PCRT). METHODS: A total 53 patients with LAEC patients were included in the current study. All patients were evaluated by F-18 FDG PET/CT before and during chemoradiotherapy. The percent changes (?, %) in F-18 FDG PET/CT parameters were used to predict pCR and to calculate overall survival (OS). The predictive value for pCR of F-18 FDG PET/CT cutoff values was determined by ROC analysis. The prognostic significance was assessed using Kaplan Meier analysis. RESULTS: pCR occurred in 15 patients (28.3 %). When DeltaSUVmax > 23.5 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 % and 52.6, respectively. The AUC was 0.750 (95 % CI; 0.612-0.859), and standard error (SE) was 0.0633 (p = 0.0002). DeltaMTV resulted in 80 % sensitivity, 76.3 % specificity, and 0.731 AUC (95 % CI; 0.591-0.843, SE = 0.077, p = 0.0027) for cutoff values >25.5 %. When DeltaTLG > 44.8 % was used as cutoff, the sensitivity and specificity of F-18 FDG PET/CT for prediction of pCR were 100 and 65.8 %, respectively. The AUC was 0.893 (95 % CI; 0.777-0.961), and SE was 0.0431 (p < 0.0001). Kaplan-Meier analysis showed that high DeltaSUVmax, DeltaMTV, and DeltaTLG were associated with improved OS. CONCLUSION: In conclusion, the current study shows the capability of the changes (Delta) in repeated F-18 FDG PET/CT parameters to predict the achievement of pCR during PCRT in LAEC patients. Among the parameters, the DeltaSUVmax, DeltaMTV, and DeltaTLG were predictors for pCR and well associated with OS. PMID- 26891955 TI - An embryonic atrazine exposure results in reproductive dysfunction in adult zebrafish and morphological alterations in their offspring. AB - The herbicide atrazine, a suspected endocrine disrupting chemical (EDC), frequently contaminates potable water supplies. Studies suggest alterations in the neuroendocrine system along the hypothalamus-pituitary-gonadal axis; however, most studies address either developmental, pubertal, or adulthood exposures, with few investigations regarding a developmental origins hypothesis. In this study, zebrafish were exposed to 0, 0.3, 3, or 30 parts per billion (ppb) atrazine through embryogenesis and then allowed to mature with no additional chemical exposure. Reproductive function, histopathology, hormone levels, offspring morphology, and the ovarian transcriptome were assessed. Embryonic atrazine exposure resulted in a significant increase in progesterone levels in the 3 and 30 ppb groups. A significant decrease in spawning and a significant increase in follicular atresia in the 30 ppb group were observed. In offspring, a decrease in the head length to body ratio in the 30 ppb group, along with a significant increase in head width to body ratio in the 0.3 and 3 ppb groups occurred. Transcriptomic alterations involved genes associated with endocrine system development and function, tissue development, and behavior. This study provides evidence to support atrazine as an EDC causing reproductive dysfunction and molecular alterations in adults exposed only during embryogenesis and morphological alterations in their offspring. PMID- 26891958 TI - Evidence for possible role of toll-like receptor 3 mediating virus-induced progression of pituitary adenomas. AB - Tumor-related viruses are known to be involved in initiation and progression of certain tumors. However, the relationship between virus and pituitary adenomas (PAs) remains unknown. Here, we investigated infection status of three types of viruses (HPV16, HHV6B and HSV1) and expression level of toll-like receptor 3 (TLR3) in 60 human PA samples. We also determined the role of TLR3 signaling pathway on a PA cell line (GH3). We firstly found that positive rates of HPV16 and HHV6B infection were significantly higher in invasive PA samples than in noninvasive samples (P < 0.01). Similarly, TLR3 mRNA and protein expression also increased in invasive PA samples (P < 0.01). In vitro analysis indicated that GH3 cell proliferation and survival were enhanced by TLR3 activation, which was accompanied by NF-kappaB activation. Our data indicate that HPV16 and HHV6B viruses may be involved in promoting the progression of PA by activating the TLR3 signaling pathway. PMID- 26891959 TI - Alu RNA accumulation in hyperglycemia augments oxidative stress and impairs eNOS and SOD2 expression in endothelial cells. AB - Endothelial dysfunction resulting from oxidative stress and inflammation plays a dominant role in hyperglycemia-induced vasculopathy. While double-stranded RNA (dsRNA) accumulates in redox and inflammatory conditions, its precise role in hyperglycemia-associated endothelial dysfunction remains unclear. This study aimed to investigate whether and how endogenous dsRNA contributes to endothelial dysfunction via oxidative stress. We used a dsRNA-specific antibody J2 to detect and immunoprecipitate cellular dsRNA. Acquired dsRNA was recognized by cDNA library construction and DNA sequencing. Quantitative PCR, ELISA and immunoassays were performed to identify changes induced by acquired dsRNA in primary human umbilical vein endothelial cells (HUVEC). Our data showed that endogenous dsRNA homologous to Alu Sc subfamily accumulated in hyperglycemic HUVEC. Comparing Alu transfected HUVEC with high-glucose treated HUVEC, we found that Alu RNA elicited the production of reactive oxygen species (ROS) and up-regulated interleukin 1beta (IL-1beta) expression and secretion in a similar manner as high-glucose treatment. Moreover, Alu RNA impeded the expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase 2 (SOD2), increased ROS production and activated nuclear factor NFkappaB by chemically scavenging ROS and inactivation of NFkappaB. The repressed expression of eNOS and SOD2 resulted from Alu RNA mediated negative regulatory mechanisms. Our study uncovered endogenous Alu RNA accumulation in hyperglycemic endothelial cells that provoked endothelial oxidative stress and dysfunction by suppressing SOD2 and eNOS expression at both transcription and translation levels via NFkappaB signaling pathway. These findings suggest a novel regulatory mechanism that involves endogenous dsRNA in endothelial oxidative stress and dysfunction. PMID- 26891960 TI - Impact of a concept map teaching approach on nursing students' critical thinking skills. AB - Nurses confront complex problems and decisions that require critical thinking in order to identify patient needs and implement best practices. An active strategy for teaching students the skills to think critically is the concept map. This study explores the development of critical thinking among nursing students in a required pathophysiology and pharmacology course during the first year of a Bachelor of Science in Nursing in response to concept mapping as an interventional strategy, using the Health Education Systems, Incorporated critical thinking test. A two-group experimental study with a pretest and posttest design was used. Participants were randomly divided into a control group (n = 42) taught by traditional didactic lecturing alone, and an intervention group (n = 41), taught by traditional didactic lecturing with concept mapping. Students in the concept mapping group performed much better on the Health Education Systems, Incorporated than students in the control group. It is recommended that deans, program directors, and nursing faculties evaluate their curricula to integrate concept map teaching strategies in courses in order to develop critical thinking abilities in their students. PMID- 26891962 TI - Pharmacological interventions for generalised itching (not caused by systemic disease or skin lesions) in pregnancy. AB - BACKGROUND: Generalised itching is one of the most common dermatological symptoms in pregnant women. Having itchy skin during pregnancy may be very frustrating and can lead to poor sleep, exhaustion and impaired quality of life. There is a need for a systematic review to evaluate the effectiveness and safety of pharmacological interventions for treating itching in pregnancy. OBJECTIVES: To assess the effectiveness and safety of pharmacological interventions for treating generalised itching (not caused by systemic diseases or skin lesions) in pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2016) and the reference list of the one identified study. SELECTION CRITERIA: All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating interventions for itching in pregnancy.Quasi-RCTs, cluster-RCTs, RCTs using a cross-over design, and studies reported in abstract form (without full text) were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the one trial report that was identified from the search strategy and this was subsequently excluded. MAIN RESULTS: There are no included studies as we did not identify any relevant trials. AUTHORS' CONCLUSIONS: Generalised itching (not caused by systemic disease or skin lesions) is quite a common symptom in pregnancy. However, there is no evidence from randomised controlled trials to guide practice in terms of the effectiveness and safety of pharmacological interventions for treating this condition.Well-designed randomised controlled trials are needed in order to evaluate the effectiveness of topical and systemic pharmacological interventions as well as any adverse effects of the interventions. Such studies should consider important outcomes such as relief of itching, women's satisfaction, sleep disturbance, and adverse effects. PMID- 26891961 TI - Relationships between ovulation rate and embryonic and placental characteristics in multiparous sows at 35 days of pregnancy. AB - The objective of this study was to investigate relationships between ovulation rate (OR) and embryonic and placental development in sows. Topigs Norsvin(r) sows (n=91, parity 2 to 17) from three different genetic backgrounds were slaughtered at 35 days of pregnancy and the reproductive tract was collected. The corpora lutea (CL) were counted and the number of vital and non-vital embryos, embryonic spacing (distance between two embryos), implantation length, placental length, placental weight and embryonic weight were assessed. The difference between number of CL and total number of embryos was considered as early embryonic mortality. The number of non-vital embryos was considered as late mortality. Relationships between OR and all other variables were investigated using two models: the first considered parity as class effect (n=91) and the second used a subset of sows with parities 4 to 10 (n=47) to analyse the genetic background as class effect. OR was significantly affected by parity (P<0.0001), but was not affected by the genetic background of the sows. Parity and genetic background did not affect embryonic and placental characteristics at 35 days of pregnancy. OR (varying from 17 to 38 CL) was positively related with early embryonic mortality (beta=0.49+/-0.1 n/ovulations, P<0.0001), with late embryonic mortality or number of non-vital embryos (beta=0.24+/-0.1 n/ovulations, P=0.001) and with the number of vital embryos (beta=0.26+/-0.1 n/ovulations, P=0.01). However, dividing OR in four classes, showed that the number of vital embryos was lowest in OR class 1 (17 to 21 CL), but not different for the other OR classes, suggesting a plateau for number of vital embryos for OR above 22. There was a negative linear relationship between OR and vital embryonic spacing (beta=-0.45+/-0.1 cm/ovulation, P=0.001), implantation length (beta=-0.35+/-0.1 cm/ovulation, P=0.003), placental length (beta=-0.38+/-0.2 cm/ovulation, P=0.05) and empty space around embryonic-placental unit (beta=-0.4+/-0.2 cm/ovulation, P=0.02), indicating uterine crowding. Further analyses showed that effects of OR on embryonic and uterine parameters were related with the increase in late mortality and not early embryonic mortality. Therefore, we conclude that a high OR results in an moderate increase in the number of vital embryos at day 35 of pregnancy, but compromises development in the surviving embryonic/placental units, suggesting that the future growth and survival of the embryos might be further compromised. PMID- 26891963 TI - The use of a robotic tibial rotation device and an electromagnetic tracking system to accurately reproduce the clinical dial test. AB - PURPOSE: The purpose of this study was to: (1) determine whether a robotic tibial rotation device and an electromagnetic tracking system could accurately reproduce the clinical dial test at 30 degrees of knee flexion; (2) compare rotation data captured at the footplates of the robotic device to tibial rotation data measured using an electromagnetic sensor on the proximal tibia. METHODS: Thirty-two unilateral ACL-reconstructed patients were examined using a robotic tibial rotation device that mimicked the dial test. The data reported in this study is only from the healthy legs of these patients. Torque was applied through footplates and was measured using servomotors. Lower leg motion was measured at the foot using the motors. Tibial motion was also measured through an electromagnetic tracking system and a sensor on the proximal tibia. Load deformation curves representing rotational motion of the foot and tibia were compared using Pearson's correlation coefficients. Off-axis motions including medial-lateral translation and anterior-posterior translation were also measured using the electromagnetic system. RESULTS: The robotic device and electromagnetic system were able to provide axial rotation data and translational data for the tibia during the dial test. Motion measured at the foot was not correlated to motion of the tibial tubercle in internal rotation or in external rotation. The position of the tibial tubercle was 26.9 degrees +/- 11.6 degrees more internally rotated than the foot at torque 0 Nm. Medial-lateral translation and anterior-posterior translation were combined to show the path of the tubercle in the coronal plane during tibial rotation. CONCLUSIONS: The information captured during a manual dial test includes both rotation of the tibia and proximal tibia translation. All of this information can be captured using a robotic tibial axial rotation device with an electromagnetic tracking system. The pathway of the tibial tubercle during tibial axial rotation can provide additional information about knee instability without relying on side-to-side comparison between knees. The translation of the proximal tibia is important information that must be considered in addition to axial rotation of the tibia when performing a dial test whether done manually or with a robotic device. Instrumented foot position cannot provide the same information. LEVEL OF EVIDENCE: IV. PMID- 26891965 TI - Back to the future: bacteriophages as promising therapeutic tools. AB - Bacteriophages (phages), natural predators of bacteria, are becoming increasingly attractive in medical and pharmaceutical applications. After their discovery almost a century ago, they have been particularly instrumental in the comprehension of basic molecular biology and genetics processes. The more recent emergence of multi-drug-resistant bacteria requires novel therapeutic strategies, and phages are being (re)considered as promising potential antibacterial tools. Furthermore, phages are also used for other purposes, e.g. vaccine production, gene/drug carriers, bacterial detection and typing. These new alternative approaches using phages are of major interest and have allowed unexpected developments, from the decipherment of fundamental biological processes to potential clinical applications. PMID- 26891964 TI - Gait analysis before and after corrective osteotomy in patients with knee osteoarthritis and a valgus deformity. AB - PURPOSE: In this prospective study, the changes in kinetics and kinematics of gait and clinical outcomes after a varus osteotomy (tibial, femoral or double osteotomy) in patients with osteoarthritis (OA) of the knee and a valgus leg alignment were analysed and compared to healthy subjects. METHODS: Twelve patients and ten healthy controls were included. Both kinetics and kinematics of gait and clinical and radiographic outcomes were evaluated. RESULTS: The knee adduction moment increased significantly postoperatively (p < 0.05) and almost similar to the control group. Patients showed less knee and hip flexion/extension motion and moment during gait pre- and postoperatively compared to the controls. A significant improvement was found in WOMAC [80.8 (SD 16.1), p = 0.000], KOS [74.9 (SD 14.7), p = 0.018], OKS [21.2 (SD 7.5), p = 0.000] and VAS-pain [32.9 (SD 20.9), p = 0.003] in all patients irrespective of the osteotomy technique used. The radiographic measurements showed a mean hip knee ankle (HKA) angle correction of 10.4 degrees (95 % CI 6.4 degrees -14.4 degrees ). CONCLUSION: In patients with knee OA combined with a valgus leg alignment, the varus-producing osteotomy is a successful treatment. Postoperatively, the patients showed kinetics and kinematics of gait similar as that of a healthy control group. A significant increase in the knee adduction moment during stance phase was found, which was related to the degree of correction. The HKA angle towards zero degrees caused a medial shift in the dynamic knee loading. The medial shift will optimally restore cartilage loading forces and knee ligament balance and reduces progression of OA or the risk of OA. A significant improvement in all clinical outcomes was also found. LEVEL OF EVIDENCE: III. PMID- 26891966 TI - Surgical treatment of primary cardiac valve tumor: early and late results in eight patients. AB - BACKGROUND: To report early and late outcomes of patients with the primary cardiac valve tumor undergoing surgical treatment over a 30-year period in our cardiovascular center. METHODS: From January 1980 to December 2014, a total of 211 patients with primary cardiac tumors accepted surgical treatments, of which only 8 (3.8 %) were primary cardiac valve tumor patients in our surgical center of cardiovascular. RESULTS: The diagnosis was identified by echocardiography preoperatively and pathological analysis postoperatively. All patients underwent intracardiac procedures with extracorporeal circulation. Intracardiac procedures included resection of tumor on leaflet in 2 patients (25 %), resection of tumor and native valvuloplasty in 2 patients (25 %), resection of neoplasm and replacement of native valve with prosthetic valve in 4 patients (50 %). One man was performed a resection of tumor on aortic noncoronary leaflet and a coronary artery bypass graft. Eight cases of primary valve tumor occurred in all of four cardiac valves. The majority of valvular tumor was myxoma in 3 cases (37.5 %), followed by the papillary fibroelastomas in 2 cases (25 %). There were one rhabdomyoma (12.5 %), one lipoma (12.5 %) and one mild malignant sarcoma (12.5 %). The mitral valve was the most commonly original valve (62.5 %). There was pulmonic (12.5 %), aortic (12.5 %) and tricuspid (12.5 %) valve tumor each one patient. There was no death and recrudescence in the series. Follow-up of all patients ranged from 1 to 16 years (mean 7.06 +/- 4.24 years). There was no recrudesce and cardiac valve dysfunction. CONCLUSION: The incidence of primary valve tumor was very low. More understanding of the rare disease and widespread use of echocardiography would greatly improve the diagnosis of primary valve tumor in the early stage. Echocardiography could detect millimeters in diameter neoplasms on cardiac valve. The diagnoses were based on imaging findings and the classical triad symptoms associated with the hemodynamic abnormalities, the organ embolism and the systemic symptoms directly from tumors. The intraoperative frozen sections and postoperative pathology analysis provided accurate diagnosis and supported the treatment strategies. Early diagnosis and intervention were keys to reserve the normal original valve function. Prompt surgical resection is necessary to prevent potential critical events. PMID- 26891967 TI - Dinutuximab: A Review in High-Risk Neuroblastoma. AB - Dinutuximab (ch14.18; UnituxinTM) is a chimeric human-mouse monoclonal antibody that binds to the glycolipid antigen disialoganglioside, which is highly expressed on the surface of neuroblastoma cells. This intravenous drug is approved in the EU and USA as combination therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-2 and isotretinoin for the postconsolidation treatment of patients with high-risk neuroblastoma. In a multinational, phase III study in this patient population, event-free survival (EFS) benefits with the dinutuximab-containing regimen versus isotretinoin alone were observed at the time of the primary (p = 0.0115) and confirmatory (p = 0.0330) efficacy analyses, although the observed p-value for the between-group difference in EFS for the primary efficacy analysis did not cross the prespecified boundary for statistical significance (p < 0.0108). Significant and sustained (5 years) overall survival benefits were seen with the dinutuximab containing regimen versus isotretinoin alone. Despite pretreatment with analgesics, antihistamines and antipyretics, serious adverse reactions have been reported with the dinutuximab-containing regimen, with infusion reactions and neuropathy prompting the US FDA to issue boxed warnings. Dinutuximab administered in combination with GM-CSF, IL-2 and isotretinoin represents an important advance in the postconsolidation treatment of patients with high-risk neuroblastoma, with its benefits outweighing its risks in a patient population with a poor prognosis and limited therapeutic options. PMID- 26891970 TI - Structure-activity correlation in transfection promoted by pyridinium cationic lipids. AB - The efficiency of the transfection of a plasmid DNA encoding a galactosidase promoted by a series of pyridinium lipids in mixtures with other cationic lipids and neutral lipids was assessed in CHO-K1 cells. We identify key molecular parameters of the lipids in the mixture - clog P, lipid length, partial molar volume - to predict the morphology of the lipid-DNA lipoplex and then correlate these same parameters with transfection efficiency in an in vitro assay. We define a Transfection Index that provides a linear correlation with normalized transfection efficiency over a series of 90 different lipoplex compositions. We also explore the influence of the same set of molecular parameters on the cytotoxicity of the formulations. PMID- 26891968 TI - Cardiovascular risk profile of patients with peripheral arterial occlusive disease during nilotinib therapy. AB - BACKGROUND: Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. OBJECTIVE: We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). PATIENTS/METHODS: We selected all cases of "vascular disorders," as the System Organ Class in MedDRA(r), in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. RESULTS: We identified 25 cases of POAD. Most of the patients were older than 60 years (84 %) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72 %). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24 months and was significantly longer in patients aged less than 60 years compared with those aged over 60 years (33.8 +/- 24.6 months vs. 22.6 +/- 17.5 months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. CONCLUSIONS: The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60 years of age; in patients younger than 60 years of age, long-term surveillance has to be maintained. PMID- 26891969 TI - Cost and quality of life analysis of HIV self-testing and facility-based HIV testing and counselling in Blantyre, Malawi. AB - BACKGROUND: HIV self-testing (HIVST) has been found to be highly effective, but no cost analysis has been undertaken to guide the design of affordable and scalable implementation strategies. METHODS: Consecutive HIV self-testers and facility-based testers were recruited from participants in a community cluster randomised trial ( ISRCTN02004005 ) investigating the impact of offering HIVST in addition to facility-based HIV testing and counselling (HTC). Primary costing studies were undertaken of the HIVST service and of health facilities providing HTC to the trial population. Costs were adjusted to 2014 US$ and INT$. Recruited participants were asked about direct non-medical and indirect costs associated with accessing either modality of HIV testing, and additionally their health related quality of life was measured using the EuroQol EQ-5D. RESULTS: A total of 1,241 participants underwent either HIVST (n = 775) or facility-based HTC (n = 446). The mean societal cost per participant tested through HIVST (US$9.23; 95 % CI: US$9.14-US$9.32) was lower than through facility-based HTC (US$11.84; 95 % CI: US$10.81-12.86). Although the mean health provider cost per participant tested through HIVST (US$8.78) was comparable to facility-based HTC (range: US$7.53-US$10.57), the associated mean direct non-medical and indirect cost was lower (US$2.93; 95 % CI: US$1.90-US$3.96). The mean health provider cost per HIV positive participant identified through HIVST was higher (US$97.50) than for health facilities (range: US$25.18-US$76.14), as was the mean cost per HIV positive individual assessed for anti-retroviral treatment (ART) eligibility and the mean cost per HIV positive individual initiated onto ART. In comparison to the facility-testing group, the adjusted mean EQ-5D utility score was 0.046 (95 % CI: 0.022-0.070) higher in the HIVST group. CONCLUSIONS: HIVST reduces the economic burden on clients, but is a costlier strategy for the health provider aiming to identify HIV positive individuals for treatment. The provider cost of HIVST could be substantially lower under less restrictive distribution models, or if costs of oral fluid HIV test kits become comparable to finger-prick kits used in health facilities. PMID- 26891971 TI - Trapping and viability of swimming bacteria in an optoelectric trap. AB - Non-contact manipulation methods capable of trapping and transporting swimming bacteria can significantly aid in chemotaxis studies. However, high swimming speed makes the trapping of these organisms an inherently challenging task. We demonstrate that an optoelectric technique, rapid electrokinetic patterning (REP), can effectively trap and manipulate Enterobacter aerogenes bacteria swimming at velocities greater than 20 MUm s(-1). REP uses electro-orientation, laser-induced AC electrothermal flow, and particle-electrode interactions for capturing these cells. In contrast to trapping non-swimming bacteria and inert microspheres, we observe that electro-orientation is critical to the trapping of the swimming cells, since unaligned bacteria can swim faster than the radially inward electrothermal flow and escape the trap. By assessing the cell membrane integrity, we study the effect of REP trapping conditions, including optical radiation, laser-induced heating, and the electric field on cell viability. When applied individually, the optical radiation and laser-induced heating have negligible effect on cells. At the standard REP trapping conditions fewer than 2% of cells have a compromised membrane after four minutes. To our knowledge this is the first study detailing the effect of REP trapping on cell viability. The presented results provide a clear guideline on selecting suitable REP parameters for trapping living bacteria. PMID- 26891972 TI - Design of nanomaterial based systems for novel vaccine development. AB - With lower cell toxicity and higher specificity, novel vaccines have been greatly developed and applied to emerging infectious and chronic diseases. However, due to problems associated with low immunogenicity and complicated processing steps, the development of novel vaccines has been limited. With the rapid development of bio-technologies and material sciences, nanomaterials are playing essential roles in novel vaccine design. Incorporation of nanomaterials is expected to improve delivery efficiency, to increase immunogenicity, and to reduce the administration dosage. The purpose of this review is to discuss the employment of nanomaterials, including polymeric nanoparticles, liposomes, virus-like particles, peptide amphiphiles micelles, peptide nanofibers and microneedle arrays, in vaccine design. Compared to traditional methods, vaccines made from nanomaterials display many appealing benefits, including precise stimulation of immune responses, effective targeting to certain tissue or cells, and desirable biocompatibility. Current research suggests that nanomaterials may improve our approach to the design and delivery of novel vaccines. PMID- 26891974 TI - A Machine Learning Framework for Plan Payment Risk Adjustment. AB - OBJECTIVE: To introduce cross-validation and a nonparametric machine learning framework for plan payment risk adjustment and then assess whether they have the potential to improve risk adjustment. DATA SOURCES: 2011-2012 Truven MarketScan database. STUDY DESIGN: We compare the performance of multiple statistical approaches within a broad machine learning framework for estimation of risk adjustment formulas. Total annual expenditure was predicted using age, sex, geography, inpatient diagnoses, and hierarchical condition category variables. The methods included regression, penalized regression, decision trees, neural networks, and an ensemble super learner, all in concert with screening algorithms that reduce the set of variables considered. The performance of these methods was compared based on cross-validated R2 . PRINCIPAL FINDINGS: Our results indicate that a simplified risk adjustment formula selected via this nonparametric framework maintains much of the efficiency of a traditional larger formula. The ensemble approach also outperformed classical regression and all other algorithms studied. CONCLUSIONS: The implementation of cross-validated machine learning techniques provides novel insight into risk adjustment estimation, possibly allowing for a simplified formula, thereby reducing incentives for increased coding intensity as well as the ability of insurers to "game" the system with aggressive diagnostic upcoding. PMID- 26891973 TI - Conjunctival Lymphoma--An International Multicenter Retrospective Study. AB - IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter study was performed. Patient data were collected from January 1, 1980, through December 31, 2010. The dates of the analysis were May 15, 2015, to August 20, 2015. The median follow-up period was 43 months. Seven eye cancer centers were involved in the study. In total, 268 patients with CL were identified, 5 of whom were excluded because of missing clinical data. MAIN OUTCOMES AND MEASURES: Overall survival, disease-specific survival, and progression-free survival were the primary end points. RESULTS: Two hundred sixty three patients with CL were included in the study. Their mean age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were frequently secondary diseases (41.7% [5 of 12] and 88.9% [16 of 18], respectively), with MCL showing a frequent occurrence of stage IVE lymphoma (61.1% [11 of 18]) and bilateral manifestation (77.8% [14 of 18]). Localized disease (stage IE or IIE) was commonly treated with external beam radiation therapy (EBRT) with or without chemotherapy, while widespread lymphoma (stage IIIE or IVE) and MCL of any stage were managed with chemotherapy with or without EBRT. Diffuse large B-cell lymphoma and MCL had a poor prognosis, with 5-year disease-specific survival of 55.0% and 9.0%, respectively, in contrast to EMZL (97.0%) and FL (82.0%). Further survival predictors included age (EMZL), sex (FL), and Ann Arbor staging classification (EMZL and FL). The American Joint Committee on Cancer TNM staging showed limited prognostic usefulness, only being able to predict survival for patients with DLBCL. CONCLUSIONS AND RELEVANCE: Conjunctival lymphoma consists of mainly 4 subtypes of B-cell non-Hodgkin lymphoma: EMZL, FL, MCL, and DLBCL. Mantle cell lymphoma is characterized by a particularly high frequency of secondary disease of stage IVE and bilateral manifestation. The histological subtype is the main outcome predictor, with MCL and DLBCL having a markedly poorer prognosis than EMZL and FL. PMID- 26891975 TI - Lenalidomide in an in vitro Dendritic Cell Model for Malignant Gliomas. AB - Malignant gliomas are tumors with a very unfavorable prognosis. They are characterized by rapid proliferation and invasion in the surrounding healthy tissue. Complete resection of the tumor is still the most important therapeutic option. Despite a variety of therapy modifications in the last years, long term survivors are still rare. Dendritic cell vaccination (DCV) might offer a new therapy option for the treatment of malignant gliomas. Hereby, tumorlysate pulsed dendritic cells (TPDC) can prime T cells to generate anti-tumor immune responses. Lenalidomide is an immune-modulatory piperidine-dione that has demonstrated activity especially in the treatment of hematopoietic malignancies. Here, we tested the combination of DCV and lenalidomide in an in vitro model for immunotherapy of malignant gliomas. No changes of T or NK cell subsets were observed when lenalidomide was used. In addition, interferon gamma enzyme linked immunospot (ELISPOT) showed no effects after priming of autologous peripheral blood mononuclear cells (PBMC) with TPDC and challenge with tumor cells. Although analyses of supernatants did not show higher amounts of interferon gamma and tumor necrosis factor alpha in the presence of lenalidomide, enhanced immune reaction by lenalidomide was detectable by granzyme B ELISPOT. Significantly higher numbers of spots were detected after challenge of TPDCprimed PBMC with tumor cells in the case that lenalidomide was present in the culture medium during priming. Our data suggest that the combination of DCV with lenalidomide might improve immunotherapy for malignant gliomas. PMID- 26891976 TI - Comparison of Molecular, Microscopic, and Culture Methods for Diagnosis of Cutaneous Leishmaniasis. AB - Cutaneous leishmaniasis (CL) is endemic in the northwest of Isfahan province, Iran. Increase in the incidence of the disease in Kashan has made it necessary to find out the best method for diagnosis and molecular characterization of Leishmania species. In the present study, 130 patients suspected to cutaneous leishmaniosis referred to health care centers of Kashan were examined. Serosity of lesion was collected for smear preparation and cultured in Novy-Nicolle-McNeal medium. DNA was extracted from serosity, and Leishmania species was determined by polymerase chain reaction (PCR) and nested PCR using kinetoplast DNA (kDNA) specific primers. The diagnostic criteria of CL were based on the observation of amastigotes in the smear, promastigotes in culture, presence of expected bands in PCR, or nested PCR. Of 130 specimens, 87 (66.9%), 72 (56.2%), 98 (75.4 %), 96 (73.8%), and 99 (76.2%) were positive for microscopic culture, PCR, nested PCR, and combined PCR and microscopy (proposed method), respectively. Sensitivity, specificity, positive and negative predictive values of PCR were 99%, 100%, 100%, 96.9%, respectively, for microscopy 87.9%, 100%, 100%, 72.1%, for culture 72.7%, 100%, 100%, 53.4 %, and for nested PCR 97%, 100%, 100%, 91.2%, respectively. Based on the results of the study, kDNA-PCR was the most sensitive method for diagnosis of CL. PMID- 26891977 TI - Selective use of corifollitropin for controlled ovarian stimulation for IVF in patients with low anti-Mullerian hormone. AB - Corifollitropin, a long-acting follicle-stimulating hormone (FSH) analogue used for in vitro fertilization (IVF), does not allow individualization of dosage, and the ovarian response is similar to around 300 IU of daily recombinant FSH. This has raised concerns about the risk of ovarian hyperstimulation syndrome (OHSS) when used in standard patients. We administered corifollitropin selectively to patients with anticipated low to moderate ovarian response based on antimullerian hormone levels in the lower quartile. The end points were oocyte distribution and occurrence of OHSS in women with AMH <=15 pmol/L. The study included a cohort of 368 patients treated in 599 cycles. Post hoc the cohort was subdivided according to AMH. With increasing baseline AMH, the number of oocytes increased from a mean of 2.7 (range 0-8 with AMH <3 pmol/L) to 6.3 (range 0-15 with AMH 10-15 pmol/L) oocytes. Cancellations of retrievals and transfers decreased significantly with increasing AMH. Overall, the ongoing live pregnancy rate per started cycle was 15.2%. None developed OHSS. No cycles were cancelled or needed triggering of ovulation using a GnRH agonist due to risk of OHSS. Selective use of corifollitropin in patients with AMH in the lower quartile is a safe and appropriate way of optimising stimulation. PMID- 26891979 TI - Dendrimer technologies for brain tumor. AB - Despite low prevalence, brain tumors are one of the most lethal forms of cancer. Unfortunately the blood-brain barrier (BBB), a highly regulated, well coordinated and efficient barrier, checks the permeation of most of the drugs across it. Hence, crossing this barrier is one of the most significant challenges in the development of efficient central nervous system therapeutics. Surface-engineered dendrimers improve biocompatibility, drug-release kinetics and aptitude to target the BBB and/or tumors and facilitate transportation of anticancer bioactives across the BBB. This review sheds light on different aspects of brain tumors and dendrimers based on different approaches for treatment including recent research, opportunities and challenges encountered in development of novel and efficient dendrimer-based therapeutics for the treatment of brain tumors. PMID- 26891978 TI - Quantifying the chameleonic properties of macrocycles and other high-molecular weight drugs. AB - Key to the pharmaceutical utility of certain macrocyclic drugs is a 'chameleonic' ability to change their conformation to expose polar groups in aqueous solution, but bury them when traversing lipid membranes. Based on analysis of the structures of 20 macrocyclic compounds that are approved oral drugs, we propose that good solubility requires a topological polar surface area (TPSA, in A(2)) of >=0.2*molecular weight (MW). Meanwhile, good passive membrane permeability requires a molecular (i.e., 3D) PSA in nonpolar environments of <=140A(2). We show that one or other of these limits is almost invariably violated for compounds with MW>600Da, suggesting that some degree of chameleonic behavior is required for most high MW oral drugs. PMID- 26891980 TI - p53 family interactions and yeast: together in anticancer therapy. AB - The p53 family proteins are among the most appealing targets for cancer therapy. A deeper understanding of the complex interplay that these proteins establish with murine double minute (MDM)2, MDMX, and mutant p53 could reveal new exciting therapeutic opportunities in cancer treatment. Here, we summarize the most relevant advances in the biology of p53 family protein-protein interactions (PPIs), and the latest pharmacological developments achieved from targeting these interactions. We also highlight the remarkable contributions of yeast-based assays to this research. Collectively, we emphasize promising strategies, based on the inhibition of p53 family PPIs, which have expedited anticancer drug development. PMID- 26891982 TI - Gene co-expression analyses: an overview from microarray collections in Arabidopsis thaliana. AB - Bioinformatics web-based resources and databases are precious references for most biological laboratories worldwide. However, the quality and reliability of the information they provide depends on them being used in an appropriate way that takes into account their specific features. Huge collections of gene expression data are currently publicly available, ready to support the understanding of gene and genome functionalities. In this context, tools and resources for gene co expression analyses have flourished to exploit the 'guilty by association' principle, which assumes that genes with correlated expression profiles are functionally related. In the case of Arabidopsis thaliana, the reference species in plant biology, the resources available mainly consist of microarray results. After a general overview of such resources, we tested and compared the results they offer for gene co-expression analysis. We also discuss the effect on the results when using different data sets, as well as different data normalization approaches and parameter settings, which often consider different metrics for establishing co-expression. A dedicated example analysis of different gene pools, implemented by including/excluding mutant samples in a reference data set, showed significant variation of gene co-expression occurrence, magnitude and direction. We conclude that, as the heterogeneity of the resources and methods may produce different results for the same query genes, the exploration of more than one of the available resources is strongly recommended. The aim of this article is to show how best to integrate data sources and/or merge outputs to achieve robust analyses and reliable interpretations, thereby making use of diverse data resources an opportunity for added value. PMID- 26891981 TI - Recent developments in using mechanistic cardiac modelling for drug safety evaluation. AB - On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making. PMID- 26891983 TI - A benchmark of gene expression tissue-specificity metrics. AB - One of the major properties of genes is their expression pattern. Notably, genes are often classified as tissue specific or housekeeping. This property is of interest to molecular evolution as an explanatory factor of, e.g. evolutionary rate, as well as a functional feature which may in itself evolve. While many different methods of measuring tissue specificity have been proposed and used for such studies, there has been no comparison or benchmarking of these methods to our knowledge, and little justification of their use. In this study, we compare nine measures of tissue specificity. Most methods were established for ESTs and microarrays, and several were later adapted to RNA-seq. We analyse their capacity to distinguish gene categories, their robustness to the choice and number of tissues used and their capture of evolutionary conservation signal. PMID- 26891984 TI - Cerebral Cortical Circuitry Formation Requires Functional Glycine Receptors. AB - The development of the cerebral cortex is a complex process that requires the generation, migration, and differentiation of neurons. Interfering with any of these steps can impair the establishment of connectivity and, hence, function of the adult brain. Neurotransmitter receptors have emerged as critical players to regulate these biological steps during brain maturation. Among them, alpha2 subunit-containing glycine receptors (GlyRs) regulate cortical neurogenesis and the present work demonstrates the long-term consequences of their genetic disruption on neuronal connectivity in the postnatal cerebral cortex. Our data indicate that somatosensory cortical neurons of Glra2 knockout mice (Glra2KO) have more dendritic branches with an overall increase in total spine number. These morphological defects correlate with a disruption of the excitation/inhibition balance, thereby increasing network excitability and enhancing susceptibility to epileptic seizures after pentylenetetrazol tail infusion. Taken together, our findings show that the loss of embryonic GlyRalpha2 ultimately impairs the formation of cortical circuits in the mature brain. PMID- 26891985 TI - Language Ability Predicts Cortical Structure and Covariance in Boys with Autism Spectrum Disorder. AB - There is significant clinical heterogeneity in language and communication abilities of individuals with Autism Spectrum Disorders (ASD). However, no consistent pathology regarding the relationship of these abilities to brain structure has emerged. Recent developments in anatomical correlation-based approaches to map structural covariance networks (SCNs), combined with detailed behavioral characterization, offer an alternative for studying these relationships. In this study, such an approach was used to study the integrity of SCNs of cortical thickness and surface area associated with language and communication, in 46 high-functioning, school-age children with ASD compared with 50 matched, typically developing controls (all males) with IQ > 75. Findings showed that there was alteration of cortical structure and disruption of fronto temporal cortical covariance in ASD compared with controls. Furthermore, in an analysis of a subset of ASD participants, alterations in both cortical structure and covariance were modulated by structural language ability of the participants, but not communicative function. These findings indicate that structural language abilities are related to altered fronto-temporal cortical covariance in ASD, much more than symptom severity or cognitive ability. They also support the importance of better characterizing ASD samples while studying brain structure and for better understanding individual differences in language and communication abilities in ASD. PMID- 26891987 TI - Acute otalgia and otorrhoea in primary care. PMID- 26891988 TI - Epilepsia partialis continua triggered by traumatic hand injury: a peripheral tuning of brain excitability? AB - Epilepsia partialis continua is often refractory to antiepileptic medication and its causal relation to peripheral sensory stimuli has only rarely been suggested. We report a man who received surgery for temporal lobe epilepsy 10 years ago, who presented "de novo" epilepsia partialis continua following mild traumatic injury of the left hand. Continuous myoclonus of the left upper limb started the day after injury and persisted unabated for several weeks. Non-invasive evaluation was inconclusive. Acute electrocorticography during surgery under local anaesthesia revealed continuous, rhythmic spiking over the right sensorimotor cortex. Tailored excision of the posterior bank of the motor and adjacent sensory cortex immediately stopped the continuous myoclonus. Histopathology showed abnormal radial lamination and was compatible with focal cortical dysplasia type IA. Epilepsia partialis continua did not recur for seven years. Afferent stimuli from peripheral injury can disinhibit hyperexcitable sensorimotor cortex leading to epilepsia partialis continua. [Published with video sequences online]. PMID- 26891990 TI - Suppression of lysyl-tRNA synthetase, KRS, causes incomplete epithelial mesenchymal transition and ineffective cell-extracellular matrix adhesion for migration. AB - The cell-adhesion properties of cancer cells can be targeted to block cancer metastasis. Although cytosolic lysyl-tRNA synthetase (KRS) functions in protein synthesis, KRS on the plasma membrane is involved in cancer metastasis. We hypothesized that KRS is involved in cell adhesion-related signal transduction for cellular migration. To test this hypothesis, colon cancer cells with modulated KRS protein levels were analyzed for cell-cell contact and cell substrate adhesion properties and cellular behavior. Although KRS suppression decreased expression of cell-cell adhesion molecules, cells still formed colonies without being scattered, supporting an incomplete epithelial mesenchymal transition. Noteworthy, KRS-suppressed cells still exhibited focal adhesions on laminin, with Tyr397-phopshorylated focal adhesion kinase (FAK), but they lacked laminin-adhesion-mediated extracellular signal-regulated kinase (ERK) and paxillin activation. KRS, p67LR and integrin alpha6beta1 were found to interact, presumably to activate ERK for paxillin expression and Tyr118 phosphorylation even without involvement of FAK, so that specific inhibition of ERK or KRS in parental HCT116 cells blocked cell-cell adhesion and cell-substrate properties for focal adhesion formation and signaling activity. Together, these results indicate that KRS can promote cell-cell and cell-ECM adhesion for migration. PMID- 26891986 TI - Genetic and Environmental Contributions to Functional Connectivity Architecture of the Human Brain. AB - One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain. PMID- 26891989 TI - cGMP Signalling Mediates Water Sensation (Hydrosensation) and Hydrotaxis in Caenorhabditis elegans. AB - Animals have developed the ability to sense the water content in their habitats, including hygrosensation (sensing humidity in the air) and hydrosensation (sensing the water content in other microenvironments), and they display preferences for specific water contents that influence their mating, reproduction and geographic distribution. We developed and employed four quantitative behavioural test paradigms to investigate the molecular and cellular mechanisms underlying sensing the water content in an agar substrate (hydrosensation) and hydrotaxis in Caenorhabditis elegans. By combining a reverse genetic screen with genetic manipulation, optogenetic neuronal manipulation and in vivo Ca(2+) imaging, we demonstrate that adult worms avoid the wetter areas of agar plates and hypo-osmotic water droplets. We found that the cGMP signalling pathway in ciliated sensory neurons is involved in hydrosensation and hydrotaxis in Caenorhabditis elegans. PMID- 26891993 TI - Corrigendum. PMID- 26891991 TI - Multicenter prospective longitudinal study of magnetic resonance biomarkers in a large duchenne muscular dystrophy cohort. AB - OBJECTIVE: The aim of this study was to describe Duchenne muscular dystrophy (DMD) disease progression in the lower extremity muscles over 12 months using quantitative magnetic resonance (MR) biomarkers, collected across three sites in a large cohort. METHODS: A total of 109 ambulatory boys with DMD (8.7 +/- 2.0 years; range, 5.0-12.9) completed baseline and 1-year follow-up quantitative MR imaging (transverse relaxation time constant; MRI-T2 ), MR spectroscopy (fat fraction and (1) H2 O T2 ), and 6-minute walk test (6MWT) measurements. A subset of boys completed additional measurements after 3 or 6 months. RESULTS: MRI-T2 and fat fraction increased significantly over 12 months in all age groups, including in 5- to 6.9-year-old boys. Significant increases in vastus lateralis (VL) fat fraction were observed in 3 and 6 months. Even in boys whose 6MWT performance improved or remained stable over 1 year, significant increases in MRI T2 and fat fraction were found. Of all the muscles examined, the VL and biceps femoris long head were the most responsive to disease progression in boys with DMD. INTERPRETATION: MR biomarkers are responsive to disease progression in 5- to 12.9-year-old boys with DMD and able to detect subclinical disease progression in DMD, even within short (3-6 months) time periods. The measured sensitivity of MR biomarkers in this multicenter study may be critically important to future clinical trials, allowing for smaller sample sizes and/or shorter study windows in this fatal rare disease. PMID- 26891994 TI - Corrigendum. PMID- 26891992 TI - Subgroup analyses in confirmatory clinical trials: time to be specific about their purposes. AB - BACKGROUND: It is well recognized that treatment effects may not be homogeneous across the study population. Subgroup analyses constitute a fundamental step in the assessment of evidence from confirmatory (Phase III) clinical trials, where conclusions for the overall study population might not hold. Subgroup analyses can have different and distinct purposes, requiring specific design and analysis solutions. It is relevant to evaluate methodological developments in subgroup analyses against these purposes to guide health care professionals and regulators as well as to identify gaps in current methodology. METHODS: We defined four purposes for subgroup analyses: (1) Investigate the consistency of treatment effects across subgroups of clinical importance, (2) Explore the treatment effect across different subgroups within an overall non-significant trial, (3) Evaluate safety profiles limited to one or a few subgroup(s), (4) Establish efficacy in the targeted subgroup when included in a confirmatory testing strategy of a single trial. We reviewed the methodology in line with this "purpose-based" framework. The review covered papers published between January 2005 and April 2015 and aimed to classify them in none, one or more of the aforementioned purposes. RESULTS: In total 1857 potentially eligible papers were identified. Forty-eight papers were selected and 20 additional relevant papers were identified from their references, leading to 68 papers in total. Nineteen were dedicated to purpose 1, 16 to purpose 4, one to purpose 2 and none to purpose 3. Seven papers were dedicated to more than one purpose, the 25 remaining could not be classified unambiguously. Purposes of the methods were often not specifically indicated, methods for subgroup analysis for safety purposes were almost absent and a multitude of diverse methods were developed for purpose (1). CONCLUSIONS: It is important that researchers developing methodology for subgroup analysis explicitly clarify the objectives of their methods in terms that can be understood from a patient's, health care provider's and/or regulator's perspective. A clear operational definition for consistency of treatment effects across subgroups is lacking, but is needed to improve the usability of subgroup analyses in this setting. Finally, methods to particularly explore benefit-risk systematically across subgroups need more research. PMID- 26891995 TI - Smoking Induced Hemolysis: Spectral and microscopic investigations. AB - Smoking is one of the major causes of lifestyle associated mortality and morbidity such as cancer of the oral cavity and lungs, and also cardiovascular diseases. In this study, we have provided evidences for the smoking-induced hemolysis using two methods: spectra of blood components and atomic force microscopic analysis of surface morphology. A total of 62 subjects (control = 31; smoker = 31: 21 male; 10 female in each set) were considered for the study. The findings indicate that smoking leads to potholes on the surface, swelling of shape, rupturing of erythrocytes, removal of hematoporphyrin and flushing into the plasma as metabolites of the erythrocyte. The overall morphology of the erythrocytes of the smoker group appears more like a Mexican hat. The mean surface roughness was 5.5 +/- 3 nm for the smoker group, but 1.2 +/- 0.2 nm for the control group. Such damages might help the toxins, (CO, peroxidants, aldehydes etc.,) to gain easy access and get strongly absorbed by the hemoglobin, leading to enhanced rates of hemolysis as shown by the spectral features of metabolites. This indicates that the average life span of the smoker's erythrocytes is significantly less than that of the control group. PMID- 26891997 TI - Genome analysis of the kiwifruit canker pathogen Pseudomonas syringae pv. actinidiae biovar 5. AB - Pseudomonas syringae pv. actinidiae (Psa) is a destructive pathogen of kiwifruit bacterial canker disease, causing severe economic losses to kiwifruit industry worldwide. Biovar 5 is the most recently reported biovar of Psa, and is found in only a local area of Japan at present. There is not much information of genetic characteristics of biovar 5. Thus, the genome of biovar 5 was sequenced and analyzed to clarify its detailed genetic characteristics. Here, the genomes of strain MAFF 212056 and MAFF 212061 of biovar 5 were estimated to be about 6.3 Mbp and 6.5 Mbp, respectively, and their phylogenetic positions were proved to be near that of biovar 2 in the phylogenetic tree. However, it was confirmed that biovar 5 had neither the coronatine biosynthetic genes conserved in biovar 2, its phylogenetic neighbor, nor the phaseolotoxin biosynthetic genes conserved in biovar 1, Japanese native pathogen. In addition, 45 genes of type III secreted effectors were identified in biovar 5 genomes, showing that their composition is different from that in the other biovars. Moreover, some biovar 5-specific regions were identified. Then, biovar 5-specific PCR primers for targeting these regions were designed, and proved to be applicable for detecting biovar 5 specifically. PMID- 26891998 TI - National Lipid Association Annual Summary of Clinical Lipidology 2016. AB - The National Lipid Association (NLA) Annual Summary of Clinical Lipidology is a yearly updated summary of principles important to the patient-centered evaluation, management, and care of patients with dyslipidemia. This summary is intended to be a "living document," with future annual updates based on emerging science, clinical considerations, and new NLA Position, Consensus, and Scientific Statements, thus providing an ongoing resource that applies the latest in medical science towards the clinical management of patients with dyslipidemia. Topics include the NLA Recommendations for Patient-Centered Management of Dyslipidemia, genetics, Familial Hypercholesterolemia, secondary causes of dyslipidemia, biomarkers and advanced lipid testing, nutrition, physical activity, obesity, adiposopathy, metabolic syndrome, diabetes mellitus, lipid pharmacotherapy, lipid altering drug interactions, lipoprotein apheresis, dyslipidemia management and treatment based upon age (children, adolescents, and older individuals), dyslipidemia considerations based upon race, ethnicity and gender, dyslipidemia and human immune virus infection, dyslipidemia and immune disorders, adherence strategies and collaborative care, and lipid-altering drugs in development. Hyperlinks direct the reader to sentinel online tables, charts, and figures relevant to lipidology, access to online atherosclerotic cardiovascular disease risk calculators, worldwide lipid guidelines, recommendations, and position/scientific statements, as well as links to online audio files, websites, slide shows, applications, continuing medical education opportunities, and patient information. PMID- 26891996 TI - Estrogen replacement therapy-induced neuroprotection against brain ischemia reperfusion injury involves the activation of astrocytes via estrogen receptor beta. AB - The incidence of ischemic stroke is significantly increased in postmenopausal women. However, the neuroprotective effects of estrogen replacement therapy (ERT) against stroke remain controversial, and the role of astrocytes in ERT has rarely been explored. In this study, we investigated the effects of estrogen and selective estrogen receptor (ER) agonists on astrocytes activation and neuronal apoptosis in mice under conditions of cell culture oxygen and glucose deprivation and reperfusion (OGD-R), and global cerebral ischemia (GCI). We demonstrated that hippocampal astrocytes primarily express ERbeta. In astrocytes, 2.5-20 nM 17beta estradiol (E2) or 10 nM DPN (ERbeta agonist) not 10 nM PPT (ERalpha agonist), significantly increased GFAP expression. And 10 nM E2, DPN or E2+MPP (ERalpha antagonist), but not PPT or E2+PHTPP (ERbeta antagonist), significantly reduced neuronal apoptosis following the subjection of astrocyte and neuronal cocultures to OGD-R. We also found that either 50 MUg/kg E2 or 8 mg/kg DPN replacement (3 weeks) significantly increased GFAP expression and reduced GCI-induced neuronal apoptosis in hippocampal CA1 region of ovariectomized mice. These results indicate that estrogen-induced neuroprotection against ischemia-reperfusion injury involves activation of astrocytes via ERbeta. Thus, the discovery and design of astrocyte-selective ERbeta modulators may offer a new strategy for ERT of ischemic stroke. PMID- 26891999 TI - Herbal preparation (HemoHIM) enhanced functional maturation of bone marrow derived dendritic cells mediated toll-like receptor 4. AB - BACKGROUND: HemoHIM, which is an herbal preparation of three edible herbs (Angelicam gigas Nakai, Cnidium offinale Makino, and Peaonia japonica Miyabe), is known to have various biological and immunological activities, but the modulatory effects of this preparation on dendritic cells (DCs)-mediated immune responses have not been examined previously. DCs are a unique group of white blood cells that initiate primary immune responses by capturing, processing, and presenting antigens to T cells. RESULTS: In the present study, we investigated the effect of HemoHIM on the functional and phenotypic maturation of murine bone marrow-derived dendritic cells (BMDCs) both in vitro and in vivo. The expression of co stimulatory molecules (CD40, CD80, CD86, MHC I, and MHC II) and the production of cytokines (IL-1beta, IL-6, IL-12p70, and TNF-alpha) were increased by HemoHIM in BMDCs. Furthermore, the antigen-uptake ability of BMDCs was decreased by HemoHIM, and the antigen-presenting ability of HemoHIM-treated mature BMDCs increased TLR4 dependent CD4(+) and CD8(+) T cell responses. CONCLUSIONS: Our findings demonstrated that HemoHIM induces TLR4-mediated BMDCs functional and phenotypic maturation through in vivo and in vitro. And our study showed the antigen presenting ability that HemoHIM-treated mature BMDCs increase CD4(+) and CD8(+) T cell responses by in vitro. These results suggest that HemoHIM has the potential to mediate DC immune responses. PMID- 26892000 TI - Metabolic and transcriptomic changes induced in host during hypersensitive response mediated resistance in rice against the Asian rice gall midge. AB - BACKGROUND: An incompatible interaction between rice (Oryza sativa) and the Asian rice gall midge (AGM, Orseolia oryzae Wood-Mason), that is usually manifested through a hypersensitive response (HR), represents an intricate relationship between the resistant host and its avirulent pest. We investigated changes in the transcriptome and metabolome of the host (indica rice variety: RP2068-18-3-5, RP), showing HR when attacked by an avirulent gall midge biotype (GMB1), to deduce molecular and biochemical bases of such a complex interaction. Till now, such an integrated analysis of host transcriptome and metabolome has not been reported for any rice-insect interaction. RESULTS: Transcript and metabolic profiling data revealed more than 7000 differentially expressed genes and 80 differentially accumulated metabolites, respectively, in the resistant host. Microarray data revealed deregulation of carbon (C) and nitrogen (N) metabolism causing a C/N shift; up-regulation of tetrapyrrole synthesis and down-regulation of chlorophyll synthesis and photosynthesis. Integrated results revealed that genes involved in lipid peroxidation (LPO) were up-regulated and a marker metabolite for LPO (azelaic acid) accumulated during HR. This coincided with a greater accumulation of GABA (neurotransmitter and an insect antifeedant) at the feeding site. Validation of microarray results by semi-quantitative RT-PCR revealed temporal variation in gene expression profiles. CONCLUSIONS: The study revealed extensive reprogramming of the transcriptome and metabolome of RP upon GMB1 infestation leading to an HR that was induced by the generation and release of reactive oxygen species i.e. singlet oxygen and resulted in LPO-mediated cell death. RP thus used HR as a means to limit nutrient supply to the feeding maggots and simultaneously accumulated GABA, strategies that could have led to maggot mortality. The integrated results of transcript and metabolic profiling, for the first time, provided insights into an HR+ type of resistance in rice against gall midge. PMID- 26892002 TI - Low level of attention to health inequalities in prevention planning activities of the Italian Regions. AB - BACKGROUND: Health promotion and prevention activities should tackle health inequalities to reduce disparities in health among disadvantaged populations. This study aimed to assess the extent to which the Italian Regions considered health inequalities during the planning of prevention activities, to detect geographical differences and to identify the possible determinants of differences in attention to health inequalities. METHODS: The 19 Regional Prevention Plans (RPPs) developed by Italian Regions within the National Prevention Plan (NPP) 2010-2013 were assessed using a specific tool to address the level of attention to health inequalities. Univariate and multivariate analyses were performed to identify regional characteristics associated with a higher level of attention to health inequalities. RESULTS: Of the 702 projects included in the 19 RPPs, only 56 (8.0 %) specifically addressed issues related to health inequalities. The results of the multivariate analysis showed that a higher level of attention was associated with the macroarea of intervention 'prevention in high-risk groups', with the higher quality of the Strategic Plan Section of the RPP and with the higher percentage of migrants in the Region in 2010. Moreover, projects that addressed the topic of health inequalities were more likely to be developed in the Northern Regions, in Regions with a lower level of 'linking social capital' and with a Higher Regional Health Care Expenditure (RHCE) as a percentage of Regional Gross Domestic Product (RGDP) in 2010. CONCLUSIONS: The level of attention to health inequalities in the regional planning process of prevention activities 2010-2013 in Italy is low. The results of this study supported the new round of prevention planning in Italy, and highlight the urgent need to increase the number of policies and interventions able to reduce health inequalities. PMID- 26892003 TI - Embedding Evidence-based Practice Education into a Post-graduate Physiotherapy Program: Eight Years of pre-Post Course Evaluations. AB - BACKGROUND AND PURPOSE: Little has been published about the effectiveness of training postgraduate physiotherapy coursework students in research methods and evidence-based practice (EBP) theory. Graduate qualities in most universities include lifelong learning. Inclusion of EBP in post-graduate coursework students' training is one way for students to develop the knowledge and skills needed to implement current best evidence in their clinical practice after graduation, thereby facilitating lifelong learning. This paper reports on change in confidence and anxiety in knowledge of statistical terminology and concepts related to research design and EBP in eight consecutive years of post-graduate physiotherapy students at one Australian university. METHODS: Pre-survey/post survey instruments were administered to students in an intensive 3-week post graduate course, which taught health research methods, biostatistics and EBP. This course was embedded into a post-graduate physiotherapy programme from 2007 to 2014. The organization and delivery of the course was based on best pedagogical evidence for effectively teaching adult physiotherapists. The course was first delivered each year in the programme, and no other course was delivered concurrently. RESULTS: There were significant improvements in confidence, significantly decreased anxiety and improvements in knowledge of statistical terminology and concepts related to research design and EBP, at course completion. Age, gender and country of origin were not confounders on learning outcomes, although there was a (non-significant) trend that years of practice negatively impacted on learning outcomes (p = 0.09). There was a greater improvement in confidence in statistical terminology than in concepts related to research design and EBP. CONCLUSION: An intensive teaching programme in health research methods and biostatistics and EBP, based on best practice adult physiotherapy learning principles, is effective immediately post-course, in decreasing anxiety and increasing confidence in the terminology used in research methods and EBP. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892001 TI - Virtual reality cue exposure for the relapse prevention of tobacco consumption: a study protocol for a randomized controlled trial. AB - BACKGROUND: Successful interventions have been developed for smoking cessation, but the success of smoking relapse prevention interventions has been limited. In particular, cognitive behavioural therapy (CBT) has been hampered by a high relapse rate. Because relapses can be due to the presence of conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality exposure therapy (VRET) can generate synthetic environments that represent risk situations for the patient in the context of relapse prevention. The primary objective of this study is to evaluate the effectiveness of CBT coupled with VRET, in comparison to CBT alone, in the prevention of smoking relapse. The secondary objectives are to assess the impact of CBT coupled with VRET on anxiety, depression, quality of life, self-esteem and addictive comorbidities (such as alcohol, cannabis, and gambling). A third objective examines the feasibility and acceptability of VR use considering elements such as presence, cybersickness and number of patients who complete the VRET program. METHOD/DESIGN: The present study is a 14-month (2 months of therapy followed by 12 months of follow-up), prospective, comparative, randomized and open clinical trial, involving two parallel groups (CBT coupled with VRET versus CBT alone). The primary outcome is the proportion of individuals with tobacco abstinence at 6 months after the end of the therapy. Abstinence is defined by the total absence of tobacco consumption assessed during a post-test interview and with an apparatus that measures the carbon monoxide levels expired. A total of 60 individuals per group will be included. DISCUSSION: This study is the first to examine the efficacy of CBT coupled with VRET in the prevention of smoking relapse. Because VRET is simple to use and has a low cost, this interactive therapeutic method might be easily implemented in clinical practice if the study confirms its efficacy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02205060 (registered 25 July 2014). PMID- 26892005 TI - Education and training to support the use of clinical telehealth: A review of the literature. AB - Introduction Despite a growing literature base, substantial investment, and policy changes within governments, the integration of telehealth into routine clinical care has been limited. The availability of appropriate systematic education and training for practitioners has been highlighted as necessary for strong adoption. However, the availability and nature of telehealth-related education and training for practitioners is not understood. By reviewing the literature, we aimed to describe the delivery of education and training in telehealth, with particular focus on content, modes of delivery, types of institutions, and target clinician groups. Methods We performed searches using PubMed, Scopus, Embase, Web of Science, PsycINFO, the Cochrane Library, and ERIC. We included studies that were focused on the delivery of telehealth-related academic or vocational education and training. We extracted information pertaining to country, programs and their participants, and tabulated the results. Results Altogether 388 articles were identified, of which nine studies were selected for final review. Programs from five countries were represented and articles were spread across telemedicine and clinically oriented journals. Education and training in telehealth has been provided as both university level and vocational courses using conventional classroom based delivery methods and e learning. Reported curriculum items included terminology, clinical applications, the evidence-base, and technological aspects. Conclusions Published evidence in peer-reviewed literature on telehealth education and training is limited. According to this review, a number of topics relating to telehealth have been covered by existing education programs both within tertiary and professional development levels. PMID- 26892006 TI - Comparative Efficacy of Newer Antidepressants in Combination with Pregabalin for Fibromyalgia Syndrome: A Controlled, Randomized Study. AB - BACKGROUND: This controlled, randomized study investigated the hypothesis that the combined use of pregabalin plus paroxetine for fibromyalgia management would be associated with comparable Somatic Symptoms Scale-8 (SSS-8) and Center for Epidemiological Studies Depression Scale (CESDS) scores, but higher tolerability than the combined use of pregabalin plus either amitriptyline or venlafaxine. METHODS: After institutional ethics committee approval, 75 female subjects diagnosed with fibromyalgia and in receipt of pregabalin (75 mg/day) were randomly allocated to concurrently receive amitriptyline (25 mg/day; n = 24), venlafaxine (75 mg/day; n = 25), or paroxetine (25 mg/day; n = 26). All patients were assessed bimonthly for 6 consecutive months for changes in SSS-8 and CESDS scores, life satisfaction, mood, sleep quality, fatigue, medication tolerability, and adverse events. RESULTS: Compared with pregabalin plus amitriptyline or venlafaxine, the combined use of pregabalin plus paroxetine in fibromyalgia patients resulted in significantly lower SSS-8 and CESDS scores from 18 (P < 0.05) and 10 weeks (P < 0.001) after the initiation of study medications, respectively; higher medication tolerability (P < 0.001); improved life satisfaction, mood, and sleep quality at most observation times (P < 0.05); and fewer instances of dry mouth and elevated blood pressure (P < 0.02). Medication termination due to poor tolerability was observed most frequently in the venlafaxine group (P < 0.05), while drowsiness, dizziness, blurred vision, abnormal taste, hunger, hallucination, urination problems, and sexual dysfunction were observed most frequently in the amitriptyline group (P < 0.02). CONCLUSION: The combined use of pregabalin plus paroxetine offers an effective method with increased tolerability to reduce the somatic and depressive symptoms of fibromyalgia and to enhance the quality of life in affected individuals. PMID- 26892007 TI - Valorization of Palm Oil Industrial Waste as Feedstock for Lipase Production. AB - The use of residues from the industrial processing of palm oil as carbon source and inducer for microbial lipase production can be a way to add value to such residues and to contribute to reduced enzyme costs. The aim of this work was to investigate the feasibility of using palm oil industrial waste as feedstock for lipase production in different cultivation systems. Evaluation was made of lipase production by a selected strain of Aspergillus niger cultivated under solid-state (SSF) and submerged fermentation (SmF). Lipase activity levels up to 15.41 IU/mL were achieved under SSF. The effects of pH and temperature on the lipase activity of the SSF extract were evaluated using statistical design methodology, and maximum activities were obtained between pH 4.0 and 6.5 and at temperatures between 37 and 55 degrees C. This lipase presented good thermal stability up to 60 degrees C and higher specificity towards long carbon chain substrates. The results demonstrate the potential application of palm oil industrial residues for lipase production and contribute to the technological advances needed to develop processes for industrial enzymes production. PMID- 26892004 TI - Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. AB - Autism spectrum disorder (ASD) is more prevalent in males, and the mechanisms behind this sex-differential risk are not fully understood. Two competing, but not mutually exclusive, hypotheses are that ASD risk genes are sex-differentially regulated, or alternatively, that they interact with characteristic sexually dimorphic pathways. Here we characterized sexually dimorphic gene expression in multiple data sets from neurotypical adult and prenatal human neocortical tissue, and evaluated ASD risk genes for evidence of sex-biased expression. We find no evidence for systematic sex-differential expression of ASD risk genes. Instead, we observe that genes expressed at higher levels in males are significantly enriched for genes upregulated in post-mortem autistic brain, including astrocyte and microglia markers. This suggests that it is not sex-differential regulation of ASD risk genes, but rather naturally occurring sexually dimorphic processes, potentially including neuron-glial interactions, that modulate the impact of risk variants and contribute to the sex-skewed prevalence of ASD. PMID- 26892008 TI - Purification, Characterization, and Optimum Conditions of Fermencin SD11, a Bacteriocin Produced by Human Orally Lactobacillus fermentum SD11. AB - Fermencin SD11, a bacteriocin produced by human orally Lactobacillus fermentum SD11, was purified, characterized, and optimized in conditions for bacterial growth and bacteriocin production. Fermencin SD11 was purified using three steps of ammonium sulfate precipitation, gel filtration chromatography, and reverse phase high-performance liquid chromatography. The molecular weight was found to be 33,000 Da using SDS-PAGE and confirmed as 33,593.4 Da by liquid chromatography mass spectrometry. Fermencin SD11 exhibited activity against a wide range of oral pathogens including cariogenic and periodontogenic pathogens and Candida. The active activity was stable between 60 - 80 degrees C in a pH range of 3.0 to 7.0. It was sensitive to proteolytic enzymes (proteinase K and trypsin), but it was not affected by alpha-amylase, catalase, lysozyme, and saliva. The optimum conditions for growth and bacteriocin production of L. fermentum SD11 were cultured at acidic with pH of 5.0-6.0 at 37 or 40 degrees C under aerobic or anaerobic conditions for 12 h. It is promising that L. fermentum SD11 and its bacteriocin may be an alternative approach for promoting oral health or prevention of oral diseases, e.g., dental caries and periodontitis, which would require further clinical trials. PMID- 26892009 TI - Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells. AB - Sec6 and Sec8, which are components of the exocyst complex, has been concerned with various roles independent of its role in secretion, such as cell migration, invadopodia formation, cytokinesis, glucose uptake, and neural development. Given the vital roles of the exocyst complex in cellular and developmental processes, the disruption of its function may be closely related to various diseases such as cancer, diabetes, and neuronal disorders. Malignant peripheral nerve sheath tumors (MPNSTs) have high malignant potential and poor prognosis because of aggressive progression and metastasis. To date, no chemotherapeutic agents have been validated for MPNSTs treatment because how MPNSTs are resistant to chemotherapeutic agents remains unknown. This study demonstrates that combination of doxorubicin and sorafenib induces apoptosis in MPNST cells through downregulation of B cell lymphoma protein 2 (Bcl-2), Bcl-2-related protein long form of Bcl-x (Bcl-xl), and myeloid cell leukemia 1 (Mcl-1). Moreover, both Sec6 and Sec8 levels decreased after treatment with doxorubicin and sorafenib and were found to be associated with Bcl-2 and Mcl-1 expressions, but not Bcl-xl. Although Sec8 was found to be involved in the regulation of both Bcl-2 and Mcl-1 at the mRNA level, Sec6 regulated Bcl-2 at the mRNA level and the binding affinity of F box and WD repeat domain containing 7 and Mcl-1, thereby controlling Mcl-1 at the protein level. Bcl-2 or Mcl-1 mRNA suppression by Sec6 or Sec8 depletion resulted in significant changes in nuclear factor-kappa B, cAMP response element, and p53 transcriptional activity. These results suggest that Sec6 and Sec8 are therapeutic target molecules in MPNST. PMID- 26892010 TI - The downside of choice: Having a choice benefits enjoyment, but at a cost to efficiency and time in visual search. AB - The efficiency of how people search for an item in visual search has, traditionally, been thought to depend on bottom-up or top-down guidance cues. However, recent research has shown that the rate at which people visually search through a display is also affected by cognitive strategies. In this study, we investigated the role of choice in visual search, by asking whether giving people a choice alters both preference for a cognitively neutral task and search behavior. Two visual search conditions were examined: one in which participants were given a choice of visual search task (the choice condition), and one in which participants did not have a choice (the no-choice condition). The results showed that the participants in the choice condition rated the task as both more enjoyable and likeable than did the participants in the no-choice condition. However, despite their preferences, actual search performance was slower and less efficient in the choice condition than in the no-choice condition (Exp. 1). Experiment 2 showed that the difference in search performance between the choice and no-choice conditions disappeared when central executive processes became occupied with a task-switching task. These data concur with a choice-impaired hypothesis of search, in which having a choice leads to more motivated, active search involving executive processes. PMID- 26892011 TI - Molecular alterations induced by a high-fat high-fiber diet in porcine adipose tissues: variations according to the anatomical fat location. AB - BACKGROUND: Changing the energy and nutrient source for growing animals may be an effective way of limiting adipose tissue expansion, a response which may depend on the genetic background of the animals. This study aims to describe the transcriptional modulations present in the adipose tissues of two pig lines divergently selected for residual feed intake which were either fed a high-fat high-fiber (HF) diet or an isocaloric low-fat high-starch diet (LF). RESULTS: Transcriptomic analysis using a porcine microarray was performed on 48 pigs (n = 12 per diet and per line) in both perirenal (PRAT) and subcutaneous (SCAT) adipose tissues. There was no interaction between diet and line on either adiposity or transcriptional profiles, so that the diet effect was inferred independently of the line. Irrespective of line, the relative weights of the two fat depots were lower in HF pigs than in LF pigs after 58 days on dietary treatment. In the two adipose tissues, the most apparent effect of the HF diet was the down-regulation of several genes associated with the ubiquitin-proteasome system, which therefore may be associated with dietary-induced modulations in genes acting in apoptotic and cell cycle regulatory pathways. Genes involved in glucose metabolic processes were also down-regulated by the HF diet, with no significant variation or decreased expression of important lipid-related genes such as the low-density lipoprotein receptor and leptin in the two fat pads. The master regulators of glucose and fatty acid homeostasis SREBF1 and MLXIPL, and peroxisome proliferator-activated receptor (PPAR)delta and its heterodimeric partner RXRA were down-regulated by the HF diet. PPARgamma which has pleiotropic functions including lipid metabolism and adipocyte differentiation, was however up-regulated by this diet in PRAT and SCAT. Dietary-related modulations in the expression of genes associated with immunity and inflammation were mainly revealed in PRAT. CONCLUSION: A high-fat high-fiber diet depressed glucose and lipid anabolic molecular pathways, thus counteracting adipose tissue expansion. Interaction effects between dietary intake of fiber and lipids on gene expression may modulate innate immunity and inflammation, a response which is of interest with regard to chronic inflammation and its adverse effects on health and performance. PMID- 26892012 TI - Non-random chromosome arrangement in triploid endosperm nuclei. AB - The endosperm is at the center of successful seed formation in flowering plants. Being itself a product of fertilization, it is devoted to nourish the developing embryo and typically possesses a triploid genome consisting of two maternal and one paternal genome complement. Interestingly, endosperm development is controlled by epigenetic mechanisms conferring parent-of-origin-dependent effects that influence seed development. In the model plant Arabidopsis thaliana, we have previously described an endosperm-specific heterochromatin fraction, which increases with higher maternal, but not paternal, genome dosage. Here, we report a detailed analysis of chromosomal arrangement and association frequency in endosperm nuclei. We found that centromeric FISH signals in isolated nuclei show a planar alignment that may results from a semi-rigid, connective structure between chromosomes. Importantly, we found frequent pairwise association of centromeres, chromosomal segments, and entire arms of chromosomes in 3C endosperm nuclei. These associations deviate from random expectations predicted by numerical simulations. Therefore, we suggest a non-random chromosomal organization in the triploid nuclei of Arabidopsis endosperm. This contrasts with the prevailing random arrangement of chromosome territories in somatic nuclei. Based on observations on a series of nuclei with varying parental genome ratios, we propose a model where chromosomes associate pairwise involving one maternal and one paternal complement. The functional implications of this predicted chromosomal arrangement are discussed. PMID- 26892015 TI - Large-Scale Expansion and Differentiation of Mesenchymal Stem Cells in Microcarrier-Based Stirred Bioreactors. AB - Mesenchymal stem cells (MSCs) have emerged as an important tool for tissue engineering, thanks to their differentiation potential and their broad trophic activities. However, for clinical purposes or for relevant in vitro applications, large quantities of MSCs are required, which could hardly be reached using conventional cultivation in plastic dishes. Microcarriers have high surface to volume ratio, which enables the easy scale-up of the expansion and differentiation of MSCs. In addition, the agitation in stirred tank bioreactors limits the diffusion gradient of nutrients or morphogens, thus providing a physiologically relevant environment to favor MSC production at large scale. This work describes a simple method for the mass expansion and differentiation of MSCs, including the procedures to monitor the proliferation, metabolic status and phenotype of MSCs during suspension culture. Moreover, this work proposes suitable materials for cGMP compliant culture conditions enabling the clinical grade production of MSCs. PMID- 26892016 TI - Isolation and Culture of Embryonic Stem Cells, Mesenchymal Stem Cells, and Dendritic Cells from Humans and Mice. AB - Stem cells are cells capable of proliferation, self-renewal, and differentiation into specific phenotypes. They are an essential part of tissue engineering, which is used in regenerative medicine in case of degenerative diseases. In this chapter, we describe the methods of isolating and culturing various types of stem cells, like human embryonic stem cells (hESCs), human umbilical cord derived mesenchymal stem cells (hUC-MSCs), murine bone marrow derived mesenchymal stem cells (mBM-MSCs), murine adipose tissue derived mesenchymal stem cells (mAD MSCs), and murine bone marrow derived dendritic cells (mBMDCs). All these cell types can be used in tissue engineering techniques. PMID- 26892013 TI - Non-farnesylated B-type lamin can tether chromatin inside the nucleus and its chromatin interaction requires the Ig-fold region. AB - Lamins are thought to direct heterochromatin to the nuclear lamina (NL); however, this function of lamin has not been clearly demonstrated in vivo. To address this, we analyzed polytene chromosome morphology when artificial lamin variants were expressed in Drosophila endoreplicating cells. We found that the CaaX-motif deleted B-type lamin Dm0, but not A-type lamin C, was able to form a nuclear envelope-independent layer that was closely associated with chromatin. Other nuclear envelope proteins were not detected in this "ectopic lamina," and the associated chromatin showed a repressive histone modification maker but not a permissive histone modification marker nor RNA polymerase II proteins. Furthermore, deletion of the C-terminal lamin-Ig-fold domain prevents chromatin association with this ectopic lamina. Thus, non-farnesylated B-type lamin Dm0 can form an ectopic lamina and induce changes to chromatin structure and status inside the interphase nucleus. PMID- 26892014 TI - Drosophila Nnf1 paralogs are partially redundant for somatic and germ line kinetochore function. AB - Kinetochores allow attachment of chromosomes to spindle microtubules. Moreover, they host proteins that permit correction of erroneous attachments and prevent premature anaphase onset before bi-orientation of all chromosomes in metaphase has been achieved. Kinetochores are assembled from subcomplexes. Kinetochore proteins as well as the underlying centromere proteins and the centromeric DNA sequences evolve rapidly despite their fundamental importance for faithful chromosome segregation during mitotic and meiotic divisions. During evolution of Drosophila melanogaster, several centromere proteins were lost and a recent gene duplication has resulted in two Nnf1 paralogs, Nnf1a and Nnf1b, which code for alternative forms of a Mis12 kinetochore complex component. The rapid evolutionary divergence of centromere/kinetochore constituents in animals and plants has been proposed to be driven by an intragenome conflict resulting from centromere drive during female meiosis. Thus, a female meiosis-specific paralog might be expected to evolve rapidly under positive selection. While our characterization of the D. melanogaster Nnf1 paralogs hints at some partial functional specialization of Nnf1b for meiosis, we have failed to detect evidence for positive selection in our analysis of Nnf1 sequence evolution in the Drosophilid lineage. Neither paralog is essential, even though we find some clear differences in subcellular localization and expression during development. Loss of both paralogs results in developmental lethality. We therefore conclude that the two paralogs are still in early stages of differentiation. PMID- 26892017 TI - EGF-liposomes promote efficient EGFR targeting in xenograft colocarcinoma model. AB - AIM: Development of EGF-liposomes (LP-EGF) for selective molecules delivery in tumors expressing EGFR. MATERIAL & METHODS: In vitro cellular interaction of EGF LP and nontargeted liposomes (LP-N) was assayed at 37 and 4 degrees C in cells expressing different EGFR levels. Receptor-mediated uptake was investigated by competition with a monoclonal antibody anti-EGFR. Selective intracellular drug delivery and efficacy was tested by oxaliplatin encapsulation. In vivo biodistribution of LP-N and LP-EGF was done in xenograft model. RESULTS: LP-EGF was internalized by an active and selective mechanism through EGFR without receptor activation. Oxaliplatin LP-EGF decreased IC50 between 48 and 13% in cell EGFR+. LP-EGF was accumulated in tumor over 72 h postdosing, while LP-N in spleen. CONCLUSION: LP-EGF represents an attractive nanosystem for cancer therapy or diagnosis. PMID- 26892018 TI - A rapid and sensitive colorimetric measurement of antibiotic efficacy against Escherichia coli in vitro. AB - A common dye of prussian blue (PB) as an indicator was used to develop a colorimetric method for detecting the efficacy of the antibiotics in vitro. Considering the electronic production capacity of microbial respiration, ferricyanide was employed in transferring electrons from target microorganism of Escherichia coli (E. coli) to produce ferrocyanide. Subsequently, ferrocyanide reacted with ferric ions to form PB. In view of relationship between the PB yield and the bacterial activity, the efficacy of the antibiotics on E. coli was directly detected at 700 nm of PB absorption. When the 5% activity of antibiotics on 20 isolates of E. coli was quantified as 5% efficacy, the applied concentrations of eight antibiotics, such as cefepime, ceftriaxone sodium, cefoperazone sodium, piperacillin sodium, amoxicillin, gentamicin, amikacin and levofloxacin were 2, 2, 4, 4, 10, 4, 8 and 8 MUg mL-1, respectively. To compare with minimum inhibitory concentration results obtained by Clinical and Laboratory Standards Institute broth macrodilution method, the results of PB methods showed good agreements except with gentamicin. Paired t-test result (P) also showed that difference between two methods was statistically significant (P = 0.006). PMID- 26892019 TI - Construction and characterization of three protein-targeting expression system in Lactobacillus casei. AB - We previously reported that the beta-1,4-Mannanase (manB) gene from Bacillus pumilus functions as a good reporter gene in Lactobacillus casei. Two vectors were constructed. One carries the signal peptide of secretion protein Usp45 (SPUsp45) from Lactococcus lactis (pELSH), and the other carries the full-length S-layer protein, SlpA, from L. acidophilus (pELWH). In this work, another vector, pELSPH, was constructed to include the signal peptide of protein SlpA (SPSlpA), and the capacity of all three vectors to drive expression of the manB gene in L. casei was evaluated. The results showed that SPUsp45 is functionally recognized and processed by the L. casei secretion machinery. The SPUsp45-mediated secretion efficiency was ~87%, and SPSlpA drove the export of secreted ManB with ~80% efficiency. SPSlpA secretion was highly efficient, and expressed SlpA was anchored to the cell wall by an unknown secretion mechanism. Full-length SlpA drove the cell wall-anchored expression of an SlpA-ManB fusion protein but at a much lower level than that of protein SlpA. PMID- 26892020 TI - Protective roles of katG-homologous genes against extrinsic peroxides in Vibrio parahaemolyticus. AB - The marine foodborne enteropathogen, Vibrio parahaemolyticus, has four putative catalase genes. Function of the katG-homologous genes, katG1(VPA0768) and katG2(VPA0453), was examined using gene deletion mutants, and compared with those of the katE-homologous genes, katE1(VPA1418) and katE2(VPA0305). Bacterial growth of DeltakatG1 was significantly delayed in the presence of 200-300 MUM H2O2, and such inhibition was enhanced when incubation temperature was lowered from 37 degrees C to 22 degrees C. In the stationary phase, the DeltakatG1 strain was more susceptible to the lethal dosage of H2O2 than the DeltakatE1 strain. The minimum inhibitory concentrations and minimum bactericidal concentrations revealed that DeltakatE1/DeltakatE2 strains were more susceptible to H2O2 than the DeltakatG1/DeltakatG2 strains in exponential phase, while DeltakatG1 was more susceptible than the DeltakatE1/DeltakatE2 strains in the starved culture. This study demonstrated the chief antioxidative role of katG1 in the stationary phase and starved culture of V. parahaemolyticus, while katG1 and katG2 were also responsive to H2O2 and cumene hydroperoxide in the exponential phase. PMID- 26892021 TI - PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus. AB - Activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) is tightly regulated during various physiological processes, such as cell proliferation, survival, and differentiation, and aberrant STAT3 activation results in tumorigenesis. In this study, we identified the cancer/testis antigen PASD1 as a positive regulator of STAT3 activity. Overexpression of PASD1 activated STAT3 and potentiated IL-6-induced activation of STAT3, whereas knockdown of PASD1 had opposite effects. Endogenous coimmunoprecipitation experiments indicated that PASD1 interacted with STAT3 in the nucleus. Overexpression of PASD1 enhanced both basal and IL-6-induced STAT3 phosphorylation at Y705, whereas knockdown of PASD1 had opposite effects. Mechanistically, PASD1 competed with TC45, a nuclear protein tyrosine phosphatase, to associate with STAT3, thus inhibited TC45-mediated dephosphorylation of STAT3. Consistently, knockdown of PASD1 inhibited expression of many pro-oncogenic genes, leading to suppression of cell proliferation, anchorage-independent growth, cell migration, and tumor growth in nude mice. Our findings demonstrate that PASD1 serves as a critical nuclear positive regulator of STAT3-mediated gene expression and tumorigenesis. PMID- 26892022 TI - Interleukin-38 is released from apoptotic cells to limit inflammatory macrophage responses. AB - Different modes of cell death regulate immunity. Whereas necrotic (necroptotic, pyroptotic) cell death triggers inflammation, apoptosis contributes to its resolution. Interleukin-1 (IL-1) family cytokines are key players in this interaction. A number of IL-1 family cytokines are produced by necrotic cells to induce sterile inflammation. However, release of IL-1 family proteins from apoptotic cells to regulate inflammation was not described. Here we show that IL 38, a poorly characterized IL-1 family cytokine, is produced selectively by human apoptotic cells to limit inflammation. Depletion of IL-38 in apoptotic cells provoked enhanced IL-6 and IL-8 levels and AP1 activation in co-cultured human primary macrophages, subsequently inducing Th17 cell expansion at the expense of IL-10-producing T cells. IL-38 was N-terminally processed in apoptotic cells to generate a mature cytokine with distinct properties. Both full-length and truncated IL-38 bound to X-linked interleukin-1 receptor accessory protein-like 1 (IL1RAPL1). However, whereas the IL-38 precursor induced an increase in IL-6 production by human macrophages, truncated IL-38 reduced IL-6 production by attenuating the JNK/AP1 pathway downstream of IL1RAPL1. In conclusion, we identified a mechanism of apoptotic cell-dependent immune regulation requiring IL 38 processing and secretion, which might be relevant in resolution of inflammation, autoimmunity, and cancer. PMID- 26892023 TI - Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver. AB - Mitochondria-associated endoplasmic reticulum membranes (MAM) play a key role in mitochondrial dynamics and function and in hepatic insulin action. Whereas mitochondria are important regulators of energy metabolism, the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown. In this study, we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum mitochondria contact points in mouse liver. Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A (PP-PP2A) pathway, induced mitochondria fission, and impaired respiration. Blocking MAM reduction counteracted glucose-induced mitochondrial alterations. Furthermore, disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function. This glucose-sensing system is deficient in the liver of insulin resistant ob/ob and cyclophilin D-KO mice, both characterized by chronic disruption of MAM integrity, mitochondrial fission, and altered mitochondrial respiration. These data indicate that MAM contribute to the hepatic glucose sensing system, allowing regulation of mitochondria dynamics and function during nutritional transition. Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance. PMID- 26892024 TI - Extraocular muscle injury during endoscopic sinus surgery: an ophthalmologic perspective. AB - PurposeThe purpose of this study is to describe the clinical characteristics and treatment results of medial rectus muscle (MR) transection incurred during endoscopic sinus surgery.MethodsThis retrospective study included 16 patients with MR transection incurred during endoscopic sinus surgery between 1994 and 2015. The operative notes of the surgical procedure, the pattern of strabismus, the type of muscle injury, the type of corrective strabismus surgery, and the surgical outcomes were reviewed.ResultsNine patients had partial resection of MR and seven patients had complete transection of MR, resulting from an injury incurred during endoscopic sinus surgery. Three of the nine patients with partial resection injury were initially diagnosed as complete resection and subsequently re-diagnosed as partial resection in a review of the images during this study. Five of the nine patients with partial MR resection underwent only simple recession/resection surgery. Patients with complete MR transection underwent muscle transposition or globe fixation surgeries and often multiple operations were required.ConclusionsThe results of this study showed that the treatment strategies could vary depending on the nature of muscle injury. In cases with complete transection, muscle transposition or globe fixation surgeries are often required, with multiple operations. However, partial muscle resection with only simple recession/resection surgery shows a favorable outcome in many cases. The use of proper imaging techniques, a thorough review of the images with various planes, and close follow-up are important for determining the nature of the muscle injury. PMID- 26892025 TI - Adjusting for unmeasured confounding due to either of two crossed factors with a logistic regression model. AB - Motivated by an investigation of the effect of surface water temperature on the presence of Vibrio cholerae in water samples collected from different fixed surface water monitoring sites in Haiti in different months, we investigated methods to adjust for unmeasured confounding due to either of the two crossed factors site and month. In the process, we extended previous methods that adjust for unmeasured confounding due to one nesting factor (such as site, which nests the water samples from different months) to the case of two crossed factors. First, we developed a conditional pseudolikelihood estimator that eliminates fixed effects for the levels of each of the crossed factors from the estimating equation. Using the theory of U-Statistics for independent but non-identically distributed vectors, we show that our estimator is consistent and asymptotically normal, but that its variance depends on the nuisance parameters and thus cannot be easily estimated. Consequently, we apply our estimator in conjunction with a permutation test, and we investigate use of the pigeonhole bootstrap and the jackknife for constructing confidence intervals. We also incorporate our estimator into a diagnostic test for a logistic mixed model with crossed random effects and no unmeasured confounding. For comparison, we investigate between within models extended to two crossed factors. These generalized linear mixed models include covariate means for each level of each factor in order to adjust for the unmeasured confounding. We conduct simulation studies, and we apply the methods to the Haitian data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892026 TI - Evidence for spinal N-methyl-d-aspartate receptor involvement in prolonged chemical nociception in the rat. AB - We used in vivo electrophysiology and a model of more persistent nociceptive inputs to monitor spinal cord neuronal activity in anaesthetised rats to reveal the pharmacology of enhanced pain signalling. The study showed that all responses were blocked by non-selective antagonism of glutamate receptors but a selective and preferential role of the N-methyl-d-aspartate (NMDA) receptor in the prolonged plastic responses was clearly seen. The work lead to many publications, initially preclinical but increasingly from patient studies, showing the importance of the NMDA receptor in central sensitisation within the spinal cord and how this could relate to persistent pain states. This article is part of a Special Issue entitled SI:50th Anniversary Issue. PMID- 26892027 TI - PDZ1 inhibitor peptide protects neurons against ischemia via inhibiting GluK2-PSD 95-module-mediated Fas signaling pathway. AB - Respecting the selective inhibition of peptides on protein-protein interactions, they might become potent methods in ischemic stroke therapy. In this study, we investigated the effect of PDZ1 inhibitor peptide on ischemic neuron apoptosis and the relative mechanism. Results showed that PDZ1 inhibitor peptide, which significantly disrupted GluK2-PSD-95 interaction, efficiently protected neuron from ischemia/reperfusion-induced apoptosis. Further, PDZ1 inhibited FasL expression, DISC assembly and activation of Caspase 8, Bid, Caspase 9 and Caspase 3 after global brain ischemia. Based on our previous report that GluK2-PSD-95 pathway increased FasL expression after global brain ischemia, the neuron protection effect of PDZ1 inhibitor peptide was considered to be achieved by disrupting GluK2-PSD-95 interaction and subsequently inhibiting FasL expression and Fas apoptosis pathway. PMID- 26892028 TI - Back pain prevalence in adolescent athletes. AB - The research aimed to investigate back pain (BP) prevalence in a large cohort of young athletes with respect to age, gender, and sport discipline. BP (within the last 7 days) was assessed with a face scale (face 1-2 = no pain; face 3-5 = pain) in 2116 athletes (m/f 61%/39%; 13.3 +/- 1.7 years; 163.0 +/- 11.8 cm; 52.6 +/- 13.9 kg; 4.9 +/- 2.7 training years; 8.4 +/- 5.7 training h/week). Four different sports categories were devised (a: combat sports, b: game sports; c: explosive strength sport; d: endurance sport). Analysis was described descriptively, regarding age, gender, and sport. In addition, 95% confidence intervals (CI) were calculated. About 168 (8%) athletes were allocated into the BP group. About 9% of females and 7% of males reported BP. Athletes, 11-13 years, showed a prevalence of 2-4%; while prevalence increased to 12-20% in 14- to 17-year olds. Considering sport discipline, prevalence ranged from 3% (soccer) to 14% (canoeing). Prevalences in weight lifting, judo, wrestling, rowing, and shooting were >=10%; in boxing, soccer, handball, cycling, and horse riding, <=6%. 95% CI ranged between 0.08-0.11. BP exists in adolescent athletes, but is uncommon and shows no gender differences. A prevalence increase after age 14 is obvious. Differentiated prevention programs in daily training routines might address sport discipline specific BP prevalence. PMID- 26892029 TI - Application of multiwalled carbon nanotubes as sorbents for the extraction of mycotoxins in water samples and infant milk formula prior to high performance liquid chromatography mass spectrometry analysis. AB - In this work, a simple and environmental friendly methodology has been developed for the analysis of a group of six mycotoxins with estrogenic activity produced by Fusarium species (i.e. zearalanone, zearalenone, alpha-zearalanol, beta zearalanol, alpha-zearalenol, and beta-zearalenol), using microdispersive SPE the symbol micro should de before dSPE with multiwalled carbon nanotubes as sorbent. Separation, determination, and quantification were achieved by HPLC coupled to ion trap MS with an ESI interface. Parameters affecting the extraction efficiency of u-dSPE such as pH of the sample, amount of multiwalled carbon nanotubes, and type and volume of elution solvent, were studied and optimized. The methodology was validated for mineral, pond, and wastewater as well as for powdered infant milk using 17beta-estradiol-2,4,16,16,17-d5 (17beta-E2 -D5 ) as internal standard, obtaining recoveries ranging from 85 to 120% for the three types of water samples and from 77 to 115% for powdered infant milk. RSD values were lower than 10%. The LOQs achieved were in the range 0.05-2.90 MUg/L for water samples and 2.02-31.9 MUg/L for powdered infant milk samples. PMID- 26892031 TI - Comment on: High stop-bang questionnaire scores predict intraoperative and early postoperative adverse events. PMID- 26892030 TI - Neural basis of uncertain cue processing in trait anxiety. AB - Individuals with high trait anxiety form a non-clinical group with a predisposition for an anxiety-related bias in emotional and cognitive processing that is considered by some to be a prerequisite for psychiatric disorders. Anxious individuals tend to experience more worry under uncertainty, and processing uncertain information is an important, but often overlooked factor in anxiety. So, we decided to explore the brain correlates of processing uncertain information in individuals with high trait anxiety using the learn-test paradigm. Behaviorally, the percentages on memory test and the likelihood ratios of identifying novel stimuli under uncertainty were similar to the certain fear condition, but different from the certain neutral condition. The brain results showed that the visual cortex, bilateral fusiform gyrus, and right parahippocampal gyrus were active during the processing of uncertain cues. Moreover, we found that trait anxiety was positively correlated with the BOLD signal of the right parahippocampal gyrus during the processing of uncertain cues. No significant results were found in the amygdala during uncertain cue processing. These results suggest that memory retrieval is associated with uncertain cue processing, which is underpinned by over-activation of the right parahippocampal gyrus, in individuals with high trait anxiety. PMID- 26892032 TI - Trace elements in farmed fish (Cyprinus carpio, Ctenopharyngodon idella and Oncorhynchus mykiss) from Beijing: implication from feed. AB - Concentrations of 30 trace elements, Li, V, Cr, Mn, Fe, Ni, Cu, Mo, Zn, Se, Sr, Co, Al, Ti, As, Cs, Sc, Te, Ba, Ga, Pb, Sn, Cd, Sb, Ag, Tm, TI, Be, Hg and U in major cultured freshwater fish species (common carp-Cyprinus carpio, grass carp Ctenopharyngodon idella and rainbow trout-Oncorhynchus mykiss) with the corresponding feed from 23 fish farms in Beijing, China, were investigated. The results revealed that Fe, Zn, Cu, Mn, Sr, Se were the major accumulated essential elements and Al, Ti were the major accumulated non-essential elements, while Mo, Co, Ga, Sn, Cd, Sb, Ag, Tm, U, TI, Be, Te, Pb and Hg were hardly detectable. Contents of investigated trace elements were close to or much lower than those in fish from other areas in China. Correlation analysis suggested that the elemental concentrations in those fish species were relatively constant and did not vary much with the fish feed. In comparison with the limits for aquafeeds and fish established by Chinese legislation, Cd in 37.5% of rainbow trout feeds and As in 20% of rainbow trout samples exceeded the maximum limit, assuming that inorganic As accounts for 10% of total As. Further health risk assessment showed that fish consumption would not pose risks to consumers as far as non-essential element contaminants are concerned. However, the carcinogenic risk of As in rainbow trout for the inhabitants in Beijing exceeded the acceptable level of 10(-)(4), to which more attention should be paid. PMID- 26892033 TI - Icariin displays anticancer activity against human esophageal cancer cells via regulating endoplasmic reticulum stress-mediated apoptotic signaling. AB - In this study, we investigated the antitumor activity of icariin (ICA) in human esophageal squamous cell carcinoma (ESCC) in vitro and in vivo and explored the role of endoplasmic reticulum stress (ERS) signaling in this activity. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human EC109 and TE1 ESCCs. Additionally, ICA exhibited strong antitumor activity, as evidenced by reductions in cell migration, adhesion, and intracellular glutathione (GSH) levels and by increases in the EC109 and TE1 cell apoptotic index, Caspase 9 activity, reactive oxygen species (ROS) level, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. Furthermore, ICA treatments upregulated the levels of ERS-related molecules (p-PERK, GRP78, ATF4, p-eIF2alpha, and CHOP) and a pro-apoptotic protein (PUMA) and simultaneously downregulated an anti-apoptotic protein (Bcl2) in the two ESCC cell lines. The downregulation of ERS signaling using eIF2alpha siRNA desensitized EC109 and TE1 cells to ICA treatment, and the upregulation of ERS signaling using thapsigargin sensitized EC109 and TE1 cells to ICA treatment. In summary, ERS activation may represent a mechanism of action for the anticancer activity of ICA in ESCCs, and the activation of ERS signaling may represent a novel therapeutic intervention for human esophageal cancer. PMID- 26892036 TI - Visible-Light-Induced Specific Desulfurization of Cysteinyl Peptide and Glycopeptide in Aqueous Solution. AB - Visible-light-induced specific desulfurization of cysteinyl peptides has been explored. The photocatalytic desulfurization catalyzed by Ru(bpy)3(2+) can proceed efficiently at room temperature in aqueous solution or in binary mixtures of aqueous/organic solvent and be compatible with the presence of residues of amino acids, carbohydrates, and various sulfur-containing functional groups. This approach was successfully applied to synthesize linear and cyclic peptides through the ligation-desulfurization protocol. PMID- 26892035 TI - Evaluation of the Compulsive Exercise Test (CET) in Adolescents with Eating Disorders: Factor Structure and Relation to Eating Disordered Psychopathology. AB - OBJECTIVE: The aims of this study were to explore the factor structure of the Compulsive Exercise Test (CET) in a clinical sample of Swedish adolescents with eating disorders (ED) and to study the relationship of CET with ED cognitions, body weight and exercise frequency. METHODS: The compulsive Exercise Test, the Eating Disorders Examination-Questionnaire, body mass index (BMI) and exercise frequency were available at assessment of 210 adolescents (age 14.4 +/- 1.6 years) with ED. RESULTS: Factor analysis generated four factors with close similarity to factors previously obtained in a community sample of adolescents samples and supported the use of the original version of CET. Exercise for weight control was strongly related to ED cognitions but less to exercise frequency and BMI. Exercise for regulation of mood was related to ED cognitions and exercise frequency but not to BMI. DISCUSSION: In adolescents with ED, different aspects of exercise are related to ED cognitions. This needs addressing in the treatment of adolescents with ED. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 26892034 TI - Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies. AB - The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I-IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are not included in the current guidelines that can be used for selected categories of patients based on their disease phenotype, clinician experience and access to new biologic therapies. PMID- 26892037 TI - RT-qPCR demonstrates light-dependent AtRBCS1A and AtRBCS3B mRNA expressions in Arabidopsis thaliana leaves. AB - Reverse transcription quantitative polymerase chain reaction (RT-qPCR) is widely used in diagnosis and research to determine specific mRNA expressions in cells. As RT-qPCR applications increase, it's necessary to provide undergraduates hands on experience of this modern technique. Here, we report a 3-week laboratory exercise using RT-qPCR to demonstrate the light-dependent expressions of AtRBCS1A and AtRBCS3B genes encoding two Arabidopsis thaliana small subunits of the ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). In the first week, students purified and quantified total RNA from leaves of A. thaliana pretreated in the dark for 96 hr and untreated controls. In the second week, RNA samples were separated by formaldehyde gel electrophoresis and used for RT-qPCR. Students calculated expressions of the two genes in dark treated leaves as percentages of those of the controls by using the 2(-DeltaDeltaC) T method and the collected CT s. In the third week, class CT s, melting curves, students' calculations, and factors affecting the reliability of RT-qPCR results were summarized and discussed. Students' results show that (i) relatively pure and intact RNA samples are obtained; (ii) ACTIN2 is a better reference gene than the 18S rRNA; (iii) the dark treatment reduces both gene expressions to < 1%; (iv) the reduction in the expression of AtRBCS3B is significantly more than that of the AtRBCS1A. Results from pre- and post-lab tests indicate that besides the theory, this exercise helps students learn the applications and associated techniques of RT-qPCR. Future modifications and new experiments that can be developed based on students' learning outcomes and assessment are also discussed. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):405-411, 2016. PMID- 26892038 TI - Oxidation of cholesterol and O-protected derivatives by the environmental pollutant NO2. AB - Exposure of O-protected and free cholesterol to NO2 under exclusion of water leads to nitroimine nitrates through a non-radical mechanism, which reveals the high susceptibility of the pi system to oxidative damage. In the presence of moisture the reaction leads to 6-nitrocholesterols , which result from hydrolysis and oxidation of 2. PMID- 26892039 TI - Awareness and Knowledge of Emergent Ophthalmic Disease Among Patients in an Internal Medicine Clinic. AB - IMPORTANCE: Emergent ophthalmic disease can lead to permanent visual impairment or blindness if medical attention is delayed. Awareness and knowledge of emergent ophthalmic disease may be important for early medical presentation and maximization of visual prognosis in some cases. OBJECTIVE: To assess public awareness and knowledge of 4 emergent ophthalmic diseases. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted from June 1 to July 30, 2015, in the waiting rooms of the outpatient internal medicine resident clinic at Mount Sinai Hospital. A written survey was administered to evaluate awareness and knowledge of retinal detachment, acute angle-closure glaucoma, giant cell arteritis, and central retinal artery occlusion. Awareness of each disease was assessed by whether participants knew what the diseases were (yes or no). Knowledge was evaluated by responses to 3 questions for each disease, including 1 question about basic pathophysiologic features, 1 question about basic symptoms, and 1 question about basic treatment options. All English-speaking patients who were physically and cognitively able to fill out the survey without assistance were considered eligible and offered the opportunity to participate during times of survey distribution; 237 completed the survey. Demographic information, including age, sex, race, income, and educational level, was collected. Data were assessed from August 1 to 7, 2015. MAIN OUTCOMES AND MEASURES: Awareness of each ophthalmic disease was determined by the proportion of respondents who answered yes, and knowledge was determined by the proportion of aware respondents who answered the knowledge questions correctly. RESULTS: Two hundred thirty-seven patients (of 227 who gave complete demographic information, 76 men [33.5%], 151 women [66.5%], and mean [SD] age, 51.3 [16.8] years) completed the survey. Awareness of each of the diseases studied was low; 61 of 220 respondents (27.7%; 95% CI, 21.8%-33.6%) were aware of retinal detachment; 32 of 219 respondents (14.6%; 95% CI, 9.9%-19.3%), acute angle-closure glaucoma; 11 of 216 respondents (5.1%; 95% CI, 2.2%-8.0%), giant cell arteritis; and 10 of 218 respondents (4.6%; 95% CI, 1.8%-7.4%), central retinal artery occlusion. Respondents who were aware and knowledgeable ranged from 29 of 199 (14.6%) for the pathophysiologic features of retinal detachment, 1 of 208 (0.5%) for the symptoms and 2 of 203 (1.0%) for treatment of giant cell arteritis, and 1 of 193 (0.5%) for the pathophysiologic features of central retinal artery occlusion. CONCLUSIONS AND RELEVANCE: Levels of awareness and knowledge of emergent ophthalmic diseases are low. These results indicate a need to educate the public about these acutely vision-threatening entities to ensure early medical presentation, to achieve the best possible visual prognosis, and to preserve quality of life. PMID- 26892040 TI - Vertebral fracture assessment by DXA is inferior to X-ray in clinical severe osteoporosis. AB - Spine fractures are diagnosed by X-ray or vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) scanning. The use of VFA evaluation by DXA is still debated. We demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine and therefore with a reduced diagnostic performance in detecting fractures. INTRODUCTION: Vertebral fracture assessment (VFA) by DXA has been evaluated for many years, and its use in clinical practice is still debated. In a cross-sectional setting, we aimed to compare VFA with traditional radiography in vertebral fracture (VF) diagnosis in severe osteoporotic patient. METHODS: A total of 207 patients referred to the outpatient clinic for teriparatide treatment were screened, out of whom 35 (16.9 %) severe osteoporotic patients were identified (mean age 67.5 +/- 11.3 years and median T-score -3.2 interquartile range (IQR) (-1.9 to -3.7). VF diagnosis was performed independently using VFA and X-ray in accordance with the semiquantitative (SQ) approach. The same technician performed the primary interpretation on both sets of images, after which a radiologist and an endocrinologist reviewed the evaluation for a conclusive judgement. RESULTS: In total, 180 radiographic fractures were detected, corresponding to 5.1 fractures per individual. Using VFA, 18.5 % of vertebrae were considered unreadable, compared to 2.0 % on X-ray. The accuracy of VFA in VF detection using X-ray as a reference resulted in sensitivity and specificity of 75.5 and 86.7 %, respectively. Sensitivity decreased from the lumbar to thoracic level. Nevertheless, VFA only identified fractures consistently between Th11 and L3. CONCLUSION: Our data, based on a severe osteoporotic population, demonstrate that VFA is inferior relative to X-ray in visualizing vertebrae properly in the upper spine, resulting in vertebrae not being assessable for analysis and a reduced diagnostic performance in detecting fractures. Improvements in DXA techniques are needed for it to be comparable with X-ray in VF diagnosis. PMID- 26892041 TI - Severe non-infective systemic inflammatory response syndrome, shock, and end organ dysfunction after zoledronic acid administration in a child. AB - INTRODUCTION: Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. Its safety profile compares well with pamidronate in pediatric patients. We describe an acute, severe, life-threatening, inflammatory reaction in a child. METHODS: A 7-year-old boy with complex medical problems and chronic ventilator requirements was admitted to the pediatric intensive care unit (due to ventilator needs) for zoledronic acid infusion and subsequent monitoring. His history was significant for osteoporosis secondary to immobilization with multiple fractures since 2 years of age, hypoxic-ischemic encephalopathy, quadriplegic cerebral palsy, seizure disorder, ventilator dependence, and pulmonary hypertension. He had previously been treated with four cycles of pamidronate without adverse events. He received 0.013 mg/kg of zoledronic acid infused over 30 minutes. Beginning 3 hours after completion of the infusion, he developed progressive tachycardia, fever, hypotension requiring vasopressor infusion, and increasing oxygen requirements. Laboratory studies revealed leukopenia, thrombocytopenia, elevated C-reactive protein, abnormal coagulation profile, metabolic acidosis, and negative cultures. The following day, he developed moderate acute respiratory distress syndrome and pulmonary hemorrhage requiring higher ventilatory settings, and subsequently diarrhea and abdominal distension. Initial clinical resolution was noted from the third day onward, and he was discharged on the sixth day after zoledronate administration. RESULTS: Our pediatric patient demonstrated an acute, severe, life-threatening reaction to zoledronic acid requiring intensive cardiorespiratory support without an underlying pre-existing inflammatory disorder. CONCLUSION: Our case highlights the importance of careful monitoring of children following zoledronic acid therapy. We recommend inpatient observation after an initial infusion of zoledronic acid in medically complex children. Children and their parents should be thoroughly counseled on the potential risks of bisphosphonate treatment, which can sometimes be severe and life threatening. PMID- 26892048 TI - Relationship between tumour location and preoperative seizure incidence depends on glioma grade of malignancy. PMID- 26892044 TI - THE PREVALENCE OF CONSANGUINEOUS MARRIAGES AND AFFECTING FACTORS IN TURKEY: A NATIONAL SURVEY. AB - This study was carried out by the Turkish Republic Ministry of Health to determine the prevalence of consanguineous marriage and its correlates with socio demographic and obstetric risk factors in women in Turkey. The cross-sectional, national-level study was carried out from October to December 2013. The study population was composed of women between the ages of 15 and 65 years living in Turkey. The sample size was calculated as 9290 houses within Turkey's 81 provinces so as to improve the Turkish rural-urban expectations by means of systematic stack sampling according to the Turkish Statistical Institute's address-based vital statistics system. The target sample size was 6364, but only eligible 4913 women, who had been married, were included in the study. The consanguineous marriage frequency in the sample was found to be 18.5%, and of these 57.8% were first cousin marriages. Women living in an extended family and whose education level and first marriage ages were low, and whose perceived economic status was poor, had higher frequencies of consanguineous marriage (p<0.001). Consanguineous marriage frequencies were higher (p<0.001) for women who had spontaneous abortions and stillbirths or who had given birth to infants with a congenital abnormality. In this context, it is important to develop national policies and strategies to prevent consanguineous marriages in Turkey. PMID- 26892049 TI - Electronic health record--a step in the right direction. PMID- 26892050 TI - Legends in Urology. PMID- 26892051 TI - Renal biopsy for medical renal disease: indications and contraindications. AB - INTRODUCTION: Percutaneous renal biopsy (PRB) is a safe and effective modality for sampling kidney tissue. In limited circumstances, alternative methods for kidney biopsy may be indicated. Historical contraindications for PRB such as bleeding diathesis, morbid obesity and solitary kidney have been called into question in the literature. We present a review of the literature on PRB and the risks and benefits associated with alternatives. MATERIALS AND METHODS: A review of the literature was performed through MEDLINE and PubMed. A total of 726 articles exist under the query, "percutaneous renal biopsy." Large series describing indications, contraindications, procedural methods, and complications were extracted. To further investigate the risks of percutaneous renal biopsy on solitary kidneys, the literature on percutaneous nephrolithotomy (PCNL) and biopsy of transplant kidneys were queried. Summaries of the data were compiled and synthesized in the body of the text. RESULTS: Percutaneous renal biopsy is safe and effective in the majority of kidney units for the evaluation of medical renal disease. Rates of bleeding range from 0.3%-7.4%, and nephrectomy rates are exceedingly low (0.1%-0.5%). Bleeding rates in open and laparoscopic approaches are comparable and range from 0%-7.0%, with major complications ranging from 0% 6.1%. CONCLUSIONS: The successes of percutaneous methods have called into question traditional contraindications such as solitary kidney, bleeding diathesis, and morbid obesity. In limited cases, alternative methods may be appropriate. We present a review of the literature for the various approaches and their associated complication rates. PMID- 26892042 TI - Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis. AB - Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy. PMID- 26892043 TI - Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells. AB - Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BDeltaSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020 mediated inhibition of cell proliferation. Expression of PR-BDeltaSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BDeltaSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. PMID- 26892052 TI - Is percent seminoma associated with intraoperative morbidity during post chemotherapy RPLND? AB - INTRODUCTION: To evaluate whether varying degrees of seminomatous elements in the primary orchiectomy specimen would be predictive of patient morbidity during post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) since the desmoplastic reaction with seminoma is associated with increased intraoperative complexity. MATERIALS AND METHODS: We retrospectively identified 127 patients who underwent PC-RPLND for residual retroperitoneal masses. Clinicodemographic, intraoperative, and 30 day postoperative outcomes were compared for patients with pure seminoma (SEM), mixed germ cell tumors (GCT) containing seminoma elements (NS+SEM), and tumors with no seminoma elements (NS). Multivariate logistic regression was used to determine independent predictors of intraoperative and postoperative 30 day complications. RESULTS: We excluded 19 patients who received chemotherapy prior to orchiectomy, 2 patients with primary extragonadal GCT, and 3 patients who underwent re-do RPLND, leaving 103 patients for analysis. Fourteen patients (13.6%) had SEM, 18 (17.5%) had NS+SEM, and 71 (68.9%) had only NS elements. SEM patients were older (p = 0.03), had more intraoperative blood loss (p = 0.03), and were more likely to have residual seminomatous components in their post-chemotherapy lymph node (LN) histology (p = 0.01). Percent seminoma in the orchiectomy specimen was an independent predictor of estimated blood loss > 1.5 liters (odds ratio: 1.04, 95% confidence interval: 1.01-1.07; p = 0.013) after adjusting for age, stage, IGCCC risk category, preop chemotherapy, number and largest LN removed, need for vascular or adjacent organ resection (including nephrectomy), and LN histology. CONCLUSIONS: Higher percentage of seminoma in the orchiectomy specimen is associated with increased estimated blood loss during PC RPLND. Percent seminoma, therefore, may be a useful prognostic tool for appropriate pre-surgical planning prior to PC-RPLND. PMID- 26892053 TI - A novel nomogram for prediction of spermatogenic improvement following empiric medical therapy for moderate-severe oligospermia. AB - INTRODUCTION: To identify pre-treatment clinical variables and hormonal responses predictive of successful spermatogenic response to empiric medical therapy (EMT), then to create a nomogram to guide clinical therapy. MATERIALS AND METHODS: All men who had been treated at our institution with EMT for moderate-severe oligospermia (<= 10 million sperm/mL) from 2003 to 2014 were included in our study. Men with hypogonadotropic hypogonadism, azoospermia, or those who had varicocelectomy or had received fertility altering medications within 6 months of initiating EMT were excluded, as well as those who did not obtain a follow up semen analysis. Pre-treatment clinical variables, hormonal responses, and spermatogenic responses were assessed. Success was defined by improvements in baseline sperm concentrations as follows: (1) cryptospermia to >= 0.3 million/mL, (2) > 100% increase in sperm concentration for men with baseline concentration < 1 million/mL, or (3) a 30% increase in sperm concentration for men with a baseline concentration between 1-10 million/mL. We performed univariate analysis to evaluate for predictors of success. The Wilcoxon rank sum test was used for continuous variables and the Fisher's exact test was used for categorical variables. Multivariable logistic regression was then used to build a nomogram. RESULTS: We identified 107 men who were treated with EMT for oligospermia (<= 10 million sperm/mL) who met our inclusion criteria. Forty-five men (42%) exhibited a poor spermatogenic response to EMT and 62 men (58%) exhibited a good response. Univariate analysis did not identify significant differences in any variable between the two groups. Multivariate analysis did identify predictive combinations which allowed the development of a nomogram with a high concordance index (0.78) for predicting spermatogenic response to EMT. CONCLUSIONS: While none of the individual pre-treatment clinical variables or hormonal responses were predictive of success following EMT, analysis of multiple factors in concert yielded a clinically useful nomogram with a high concordance index. PMID- 26892054 TI - Predicting lymph node invasion in patients treated with robot-assisted radical prostatectomy. AB - INTRODUCTION: To develop a nomogram to predict lymph node invasion (LNI) in the contemporary North American patient treated with robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: We included 2,007 patients treated with RARP and pelvic lymph node dissection (PLND) at a single institution between 2008 and 2012. D'Amico low risk patients underwent an obturator and hypogastric PLND, while extended PLND was reserved for intermediate/high risk patients. Logistic regression analysis tested the relationship between LNI and all available predictors. Independent predictors of LNI were used to develop a novel nomogram. Discrimination, calibration and decision-curve analysis were used to analyze the performance of our novel nomogram, and compare it to open radical prostatectomy (ORP)-based models, namely the Godoy nomogram. RESULTS: Overall, 5.3% of our patients harbored LNI. Median number of lymph nodes removed was 6.0 (interquartile range: 4-11). The most parsimonious multivariable model to predict LNI consisted of the following independent predictors: PSA value, clinical stage, and primary and secondary Gleason scores (all p <= 0.02). The discrimination of our novel model was 86.2%, and its calibration was virtually optimal. Using a 2% nomogram cut off, 58% of patients would be spared PLND, while missing only 9.4% of individuals with LNI. The novel nomogram compared favorably to the Godoy nomogram, when discrimination, calibration and net-benefit were used as benchmarks. CONCLUSIONS: Approximately 5% of contemporary North American patients harbor LNI at RARP. Our novel nomogram can accurately identify these patients, and this may help to improve patient selection, and avoid unnecessary PLND in the majority of patients. PMID- 26892056 TI - Prognostic markers for urologic cancers. PMID- 26892055 TI - The prognostic utility of preoperative neutrophil-to-lymphocyte ratio in localized clear cell renal cell carcinoma. AB - INTRODUCTION: To explore whether the association between preoperative neutrophil to-lymphocyte ratio (NLR) elevation and worse survival is of use prognostically or merely a reflection of medical comorbidities in clear cell renal cell carcinoma (CC RCC). MATERIALS AND METHODS: We identified 1970 patients treated at Memorial Sloan Kettering Cancer Center from 1998-2012 by partial or radical nephrectomy for non-metastatic CC RCC. NLR was calculated by dividing absolute neutrophil count by absolute lymphocyte count; both were obtained from preoperative complete blood count. Uni- and multivariable Cox proportional hazards regression, which included established prognostic variables, were used to test for association between NLR and recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). RESULTS: Univariate analysis identified elevated NLR as significantly associated with worse RFS, CSS, and OS (all p < 0.0001). However, upon multivariable analysis, elevated NLR was significantly associated with only worse OS (p < 0.0001). After adding markers of comorbidity that were significantly correlated with NLR elevation-higher American Society of Anesthesiologists class (p = 0.013), older age, and higher estimated glomerular filtration rate (both p < 0.0001)--into the multivariable model, NLR remained significantly associated with OS (p = 0.001). The addition of NLR into the prognostic model for OS did not increase Harrell's concordance index from 0.776. CONCLUSIONS: In our cohort, preoperative NLR elevation is associated with worse OS, but there was no significant association with RFS or CSS on multivariable analysis. Preoperative NLR does not add unique prognostic information for patients undergoing surgical resection of renal tumors. PMID- 26892057 TI - Partial and hemi-nephrectomy for renal malignancy in patients with horseshoe kidney. AB - INTRODUCTION: Horseshoe kidney is the most common congenital renal fusion anomaly, with an estimated incidence of 1.7 to 2.5 cases per 1000 live births. In these patients, nephron-sparing surgical management of renal tumors may be complicated by abnormal renal location, aberrant vasculature, and the presence of a renal isthmus. We present the largest known series of patients with renal malignancy in horseshoe kidneys managed by partial or hemi-nephrectomy with associated outcomes. MATERIALS AND METHODS: A retrospective review of our institution's electronic medical record was conducted to identify consecutive cases over an 11 year period. Pediatric patients and those who underwent surgery for benign indications were excluded from analysis. RESULTS: Eight patients with horseshoe kidney who underwent partial or hemi-nephrectomy for renal malignancy were identified. Median tumor size was 6.0 cm (IQR 3.7 cm-9.5 cm). Six patients had clear cell renal cell carcinoma (RCC), 1 patient had papillary RCC, and 1 patient had a renal carcinoid tumor with concurrent adenocarcinoma. Median length of stay was 4 days (IQR 2-.5.5 days). Median perioperative change in eGFR was -6 mL/min/1.732 (IQR -2.6-8.6 mL/min/1.73m2). One patient developed postoperative urine leak requiring percutaneous drainage and ureteral stent placement. Median follow up was 38.5 months, with a cancer-specific survival of 87.5% and an overall survival of 62.5%. CONCLUSION: Partial and hemi-nephrectomy for renal malignancy can safely be performed in patients with horseshoe kidney with acceptable operative and oncologic outcomes. PMID- 26892058 TI - Incorporation of the da Vinci Surgical Skills Simulator at urology Objective Structured Clinical Examinations (OSCEs): a pilot study. AB - INTRODUCTION: To incorporate the da Vinci Surgical Skills Simulator (dVSSS) into Objective Structured Clinical Examinations (OSCEs) and to assess basic robotic skills of urology Post-Graduate Trainees (PGTs). MATERIALS AND METHODS: PGTs in post-graduate years (PGY-3 to PGY-5) from two Quebec urology training programs were recruited. During a 20 minute OSCE station, PGTs were asked to fill in a questionnaire and perform two tasks: pick and place, and energy dissection level 1. For each exercise, the norm-referenced method was used to establish a passing score to determine competency. The participant was considered competent in these two basic dVSSS exercises if he/she gained the passing score on both tasks. RESULTS: All nine PGTs who attended the OSCE voluntarily participated in the study. They had performed a median of 10 (IQR: 2.5-16) laparoscopic procedures, 2 (0-8) robotic procedures, and assisted 10 (IQR: 0-15) robotic procedures at the bedside prior to this OSCE. Based on a passing score of 90 for task 1 and 72 for task 2, there were 3 (33%) competent PGTs, all of whom were from PGY-5 level. Therefore, there was significant difference among PGY levels in terms of competency for the basic robotic skills tested (p = 0.01). When compared with PGTs, experts had performed significantly higher numbers of robotic procedures (5.2 +/- 2.4 versus 25 +/- 8.7; p = 0.02). However, there was no significant difference in the performance parameters between PGTs and experts in both tasks. CONCLUSION: This study confirms the feasibility of incorporating dVSSS into OSCEs to assess basic robotic skills of urology PGTs. Future studies need to include more complex exercises and larger sample size to expand on these results. PMID- 26892059 TI - Robotic VR simulation to measure competency: a step in the right direction. PMID- 26892060 TI - Magnetic resonance imaging of the ankle performed on an InterStim patient. AB - Patients undergoing InterStim implantation often have comorbidities, which require magnetic resonance imaging (MRI) for diagnosis. Although MRI of the head has been recently approved for use with the InterStim neurostimulator, imaging of other regions remains controversial. We present a case of Achilles tendinitis diagnosed on MRI of the ankle in a patient with an InterStim device. The neurostimulator was deactivated, and using a transmit/receive extremity coil, the left ankle was imaged without any adverse events. At 9 months post-imaging, the patient continued to have good control of symptoms with InterStim, with no negative effects from MRI. MRI of the ankle is feasible in patients with InterStim implants using transmit/receive coils. Further evaluation is warranted to study the safety of MRI of other body region in InterStim patients. PMID- 26892061 TI - Primary malignant melanoma of the urinary bladder and ureter. AB - Primary malignant melanoma of the urinary bladder is a rare lesion. We report the case of a 78-year-old male with no previous history of cutaneous melanoma who presented with hematuria. Further investigation with imaging and cystoscopy raised suspicion of a primary bladder and ureteric melanoma, which had subsequently metastasized. This was confirmed with histological assessment and a thorough search for alternative primary lesions. Unfortunately, our patient passed away prior to receiving any oncological treatment for his metastatic melanoma, underscoring both the high mortality of this lesion and the need for a consensus on definitive treatment. PMID- 26892062 TI - 'Spousal Revenge Syndrome'--description of a new chronic pelvic pain syndrome patient cohort. AB - Psychological factors may play a role in the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This case series describes a cohort of 10 men presenting with CP/CPPS whose symptoms began after an extramarital sexual encounter, who strongly believed they had a sexually transmitted infection (STI) despite negative testing, and who have had no improvement with empiric antibiotic treatment. Patients' clinical presentation and physical exam findings are reviewed. All men were clinically phenotyped with the UPOINT system. Pelvic floor spasm and not infection was prominent in these men. Treatment recommendations are proposed and compliance assessed. PMID- 26892063 TI - Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix. AB - The gonadotropin-releasing hormone (GnRH) receptor antagonist degarelix has several unique characteristics compared to luteinizing hormone-releasing hormone (LHRH) analogs used in the management of prostate cancer. Notable differences of GnRH receptor antagonists include no flare reaction, and a more rapid suppression of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate-specific antigen (PSA) compared to LHRH analogs. Despite emerging evidence supporting the use of GnRH receptor antagonists over the more widely used LHRH analogs in the management of prostate cancer, physicians may be reluctant to prescribe degarelix. They may be concerned about patient complaints about injection-site reactions (ISRs). The subcutaneous injection of degarelix has been associated with a higher rate of ISRs compared with the intramuscular injections of LHRH analogs. This "How I Do It" article describes techniques and strategies that have been developed by physicians and nurses to reduce the discomfort associated with the subcutaneous delivery of degarelix. PMID- 26892064 TI - Technical refinements to improve outcomes following distal hypospadias repair. AB - INTRODUCTION: Hypospadias complications, most notably meatal stenosis, are commonly reported to occur after tubularized incised plate (TIP) hypospadias repair. We focus on a point of technique in TIP repair and its effect on outcome of this possible complication, as well as other commonly reported complications. Meatal stenosis after TIP can be avoided if the urethra and overlying glans are dissected and sutured separately with no attempt at cross suturing whether the urethra ends below, behind, or above the glans sutures. This hypothesis was evaluated by a prospective data collection before and after implementation to evaluate the effect of a technical refinement on rates of meatal stenosis in TIP hypospadias repair. MATERIALS AND METHODS: All cases of coronal to midpenile hypospadias repair during two periods were included in our study. Group 1 included 140 consecutive patients over a 30 month period. Group 2 included 122 consecutive patients over a 36 month period during which the above mentioned technical changes were implemented by all participating pediatric urologists. Rates of complications between the two groups were compared with special emphasis on meatal stenosis. RESULTS: Median follow up for both groups was > 1 year. Overall complication rate in Group 1 was 31.5% compared to 9.8% in Group 2. Meatal stenosis was significantly reduced from 13 patients (9.3%) in Group 1 to 2 patients (1.6%) in Group 2, p = 0.008. CONCLUSION: The technical refinements described resulted in reduction of complication rates and a decrease in incidence of meatal stenosis. PMID- 26892065 TI - Impact of mild preoperative renal insufficiency on in-hospital and long-term outcomes after off-pump coronary artery bypass grafting: a retrospective propensity score matching analysis. AB - BACKGROUND: Mild preoperative renal insufficiency is not rare in patients receiving isolated off-pump coronary artery bypass grafting surgery (OPCAB) surgery. However, there is less study aimed to evaluate the impact of mild preoperative renal insufficiency on in-hospital and follow-up outcomes after isolated OPCAB surgery. This single-centre, retrospective propensity score matching study aimed to evaluate the impact of mild preoperative renal insufficiency on in-hospital and long-term outcomes after first isolated OPCAB surgery. METHODS: After propensity score matching, 1236 patients with preoperative estimated glomerular filtration rate (eGFR) of more than 60 ml/min/1.73 m(2) undergoing first isolated OPCAB surgery from January 2007 to December 2011 were entered into this study and were divided to normal group (eGFR >= 90 ml/min/1.73 m(2), n = 618) and mild group (eGFR of 60-89 ml/min/1.73 m(2), n = 618). The in-hospital and long-term outcomes were investigated and retrospectively analyzed. RESULTS: The 2 propensity score-matched groups had similar baseline and procedural characteristics except the baseline eGFR. Thirty five patients died during the same hospitalization or within 30 days of operation, with a surgical mortality of 2.8 %. Sixty-seven patients died during follow-up, with a long-term survival of 94.1 %. Univariate factor analysis showed that the 2 propensity score-matched groups have similar rates among in-hospital outcomes. Kaplan-Meier curves displayed a similar in-hospital survival between the 2 groups (chi(2) = 0.728, p = 0.393), while a better long-term survival in patients with normal preoperative renal function compared with mild preoperative renal insufficiency (chi(2) = 4.722, p = 0.030). After Cox proportional model was used, the hazard ratio for long-term mortality in patients with mild preoperative renal insufficiency compared with normal preoperative renal function was 1.72 (95 % CI 1.06-2.83, p = 0.032). CONCLUSIONS: Mild preoperative renal insufficiency compared with normal preoperative renal function reduced long-term survival, without evidence of worse in-hospital outcomes. PMID- 26892067 TI - Whole-body MRI: non-oncological applications in paediatrics. AB - Whole-body magnetic resonance imaging (WBMRI) is a fast and accurate method for detecting and monitoring of diseases throughout the entire body without exposure to ionizing radiation. Among emerging non-oncological potential applications of WBMRI, rheumatological diseases play an important role. Rheumatological WBMRI applications include the evaluation of chronic multifocal recurrent osteomyelitis, dermatomyositis, fever of unknown origin, arthritis, and connective tissue diseases. Aim of this review is to give an overview of the use of WBMRI in rheumatological field. PMID- 26892066 TI - Comparative genomics and functional analysis of the 936 group of lactococcal Siphoviridae phages. AB - Genome sequencing and comparative analysis of bacteriophage collections has greatly enhanced our understanding regarding their prevalence, phage-host interactions as well as the overall biodiversity of their genomes. This knowledge is very relevant to phages infecting Lactococcus lactis, since they constitute a significant risk factor for dairy fermentations. Of the eighty four lactococcal phage genomes currently available, fifty five belong to the so-called 936 group, the most prevalent of the ten currently recognized lactococcal phage groups. Here, we report the genetic characteristics of a new collection of 936 group phages. By combining these genomes to those sequenced previously we determined the core and variable elements of the 936 genome. Genomic variation occurs across the 936 phage genome, such as genetic elements that (i) lead to a +1 translational frameshift resulting in the formation of additional structures on the phage tail, (ii) specify a double neck passage structure, and (iii) encode packaging module-associated methylases. Hierarchical clustering of the gene complement of the 936 group phages and nucleotide alignments allowed grouping of the ninety 936 group phages into distinct clusters, which in general appear to correspond with their geographical origin. PMID- 26892069 TI - Nanoscale imaging of the photoresponse in PN junctions of InGaAs infrared detector. AB - Electronic layout, such as distributions of charge carriers and electric field, in PN junction is determinant for the photovoltaic devices to realize their functionality. Considerable efforts have been dedicated to the carrier profiling of this specific region with Scanning Probe Microscope, yet reliable analysis was impeded by the difficulty in resolving carriers with high mobility and the unclear surface effect, particularly on compound semiconductors. Here we realize nanometer Scanning Capacitance Microscopic study on the cross-section of InGaAs/InP photodetectors with the featured dC/dV layout of PN junction unveiled for the first time. It enables us to probe the photo-excited minority carriers in junction region and diagnose the performance deficiency of the diode devices. This work provides an illuminating insight into the PN junction for assessing its basic capability of harvesting photo-carriers as well as blocking leakage current in nanoscopic scale. PMID- 26892068 TI - Combined pulmonary fibrosis and emphysema (CPFE): what radiologist should know. AB - Combined pulmonary fibrosis and emphysema is a relatively newly defined entity, which has been deeply studied in the recent years. Despite the wide numbers of papers on this topic, there are still several open questions about pathogenesis, epidemiology, natural history and prognosis. The diagnosis could be assessed only after HRCT scan as functional tests often result in an underestimation of this syndrome. What radiologists need to know about this syndrome consists in the heterogeneity of appearances: emphysema is mainly paraseptal and fibrotic pattern could be variable, including the variant of airspace enlargement with fibrosis which needs to be differentiated from honeycombing. A special attention must be paid on complications which could worsen the prognosis, such as pulmonary hypertension and lung cancer. Further studies are needed to address if the type of fibrotic pattern as well as fibrosis CT index could be considered as prognostic factors. Thus, the role of radiologists in the management of these patients is crucial as it involves diagnosis, detection of complications and could possible concerns the identification of patients at higher risk. PMID- 26892071 TI - Using Deep Learning for Compound Selectivity Prediction. AB - Compound selectivity prediction plays an important role in identifying potential compounds that bind to the target of interest with high affinity. However, there is still short of efficient and accurate computational approaches to analyze and predict compound selectivity. In this paper, we propose two methods to improve the compound selectivity prediction. We employ an improved multitask learning method in Neural Networks (NNs), which not only incorporates both activity and selectivity for other targets, but also uses a probabilistic classifier with a logistic regression. We further improve the compound selectivity prediction by using the multitask learning method in Deep Belief Networks (DBNs) which can build a distributed representation model and improve the generalization of the shared tasks. In addition, we assign different weights to the auxiliary tasks that are related to the primary selectivity prediction task. In contrast to other related work, our methods greatly improve the accuracy of the compound selectivity prediction, in particular, using the multitask learning in DBNs with modified weights obtains the best performance. PMID- 26892070 TI - Intra-uterine insemination for unexplained subfertility. AB - BACKGROUND: Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive thAppendixan in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rate. This is an update of a Cochrane review (Veltman-Verhulst 2012) originally published in 2006 and updated in 2012. OBJECTIVES: To determine whether, for couples with unexplained subfertility, IUI improves the live birth rate compared with timed intercourse (TI), or expectant management, both with and without ovarian hyperstimulation (OH). SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (formerly Cochrane Menstrual Disorders and Subfertility Group) Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, inception to Issue 11, 2015), Ovid MEDLINE, Ovid EMBASE, PsycINFO and trial registers, all from inception to December 2015 and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. The evidence is current to December 2015. SELECTION CRITERIA: Truly randomised controlled trial (RCT) comparisons of IUI versus TI, in natural or stimulated cycles. Only couples with unexplained subfertility were included. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, quality assessment and data extraction. We extracted outcomes, and pooled data and, where possible, we carried out subgroup and sensitivity analyses. MAIN RESULTS: We included 14 trials including 1867 women. IUI versus TI or expectant management both in natural cycleLive birth rate (all cycles)There was no evidence of a difference in cumulative live births between the two groups (Odds Ratio (OR) 1.60, 95% confidence interval (CI) 0.92 to 2.78; 1 RCT; n = 334; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI was assumed to be 16%, that of IUI would be between 15% and 34%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.50, 95% CI 0.04 to 5.53; 1 RCT; n = 334; moderate quality evidence). IUI versus TI or expectant management both in stimulated cycleLive birth rate (all cycles)There was no evidence of a difference between the two treatment groups (OR 1.59, 95% CI 0.88 to 2.88; 2 RCTs; n = 208; I(2) = 72%; moderate quality evidence). The evidence suggested that if the chance of achieving a live birth in TI was assumed to be 26%, the chance of a live birth with IUI would be between 23% and 50%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rates between the two treatment groups (OR 1.46, 95% CI 0.55 to 3.87; 4 RCTs, n = 316; I(2) = 0%; low quality evidence). IUI in a natural cycle versus IUI in a stimulated cycle Live birth rate (all cycles)An increase in live birth rate was found for women who were treated with IUI in a stimulated cycle compared with those who underwent IUI in natural cycle (OR 0.48, 95% CI 0.29 to 0.82; 4 RCTs, n = 396; I(2) = 0%; moderate quality evidence). The evidence suggested that if the chance of a live birth in IUI in a stimulated cycle was assumed to be 25%, the chance of a live birth in IUI in a natural cycle would be between 9% and 21%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 0.33, 95% CI 0.01 to 8.70; 2 RCTs; n = 65; low quality evidence). IUI in a stimulated cycle versus TI or expectant management in a natural cycleLive birth rate (all cycles)There was no evidence of a difference in live birth rate between the two treatment groups (OR 0.82, 95% CI 0.45 to 1.49; 1 RCT; n = 253; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI or expectant management in a natural cycle was assumed to be 24%, the chance of a live birth in IUI in a stimulated cycle would be between 12% and 32%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the two treatment groups (OR 2.00, 95% CI 0.18 to 22.34; 2 RCTs; n = 304; moderate quality evidence). IUI in natural cycle versus TI or expectant management in stimulated cycle Live birth rate (all cycles)There was evidence of an increase in live births for IUI (OR 1.95, 95% CI 1.10 to 3.44; 1 RCT, n = 342; moderate quality evidence). The evidence suggested that if the chance of a live birth in TI in a stimulated cycle was assumed to be 13%, the chance of a live birth in IUI in a natural cycle would be between 14% and 34%.Multiple pregnancy rateThere was no evidence of a difference in multiple pregnancy rate between the groups (OR 1.05, 95% CI 0.07 to 16.90; 1 RCT; n = 342; moderate quality evidence).The quality of the evidence was assessed using GRADE methods. Quality ranged from low to moderate, the main limitation being imprecision in the findings for both live birth and multiple pregnancy.. AUTHORS' CONCLUSIONS: This systematic review did not find conclusive evidence of a difference in live birth or multiple pregnancy in most of the comparisons for couples with unexplained subfertility treated with intra-uterine insemination (IUI) when compared with timed intercourse (TI), both with and without ovarian hyperstimulation (OH). There were insufficient studies to allow for pooling of data on the important outcome measures for each of the comparisons. PMID- 26892072 TI - Social functioning in patients with a psychotic disorder and first rank symptoms. AB - There have been suggestions that a sense of self emerges through social interaction, which requires an intact capability to distinguish self from others. Here we investigated the contribution of first rank delusions and hallucinations, i.e. symptom expressions of a disturbed sense of self, to social functioning in patients with a psychotic disorder. Life-time and present-state positive symptom clusters (e.g. first rank delusions and hallucinations) and present-state negative symptoms were submitted to hierarchical multiple-regression analyses with (different domains of) social functioning as dependent variable. In addition to negative symptoms (beta=-0.48), the life-time presence of first rank delusions is significantly negative associated with level of social functioning, in particular with the quality of interpersonal interactions, with a modest standardized regression coefficient (beta=-0.14). We reconfirmed the well established relationship between negative symptoms and social functioning, but the life-time presence of first rank delusions may also have an subtle ongoing effect on the quality of the interaction with others. We propose that the experience of first rank delusions may be an expression of enduring self disturbances, leaving patients unsure on how to behave in social interactions. PMID- 26892073 TI - The Effectiveness of Incorporating a Play-based Intervention to Improve Functional Mobility for a Child with Relapsed Acute Lymphoblastic Leukaemia: A Case Report. AB - BACKGROUND AND PURPOSE: Acute lymphoblastic leukaemia (ALL) is one of the most common forms of cancer seen in children, accounting for one-fourth of all childhood cancers. These children typically present with decreased functional mobility, weakened lower extremity muscle strength and reduced exercise endurance and interests because of disease progressions and chemotherapy treatments. The purpose of this case report was to examine the effectiveness of incorporating a play-based physical therapy (PT) intervention programme to improve functional mobility for an inpatient with relapsed ALL undergoing chemotherapy. CASE DESCRIPTION: The patient was a 3-year-old male admitted to the hospital for relapsed ALL. He was diagnosed approximately 1 year earlier for which he had undergone chemotherapy and was later considered in remission at that time. When the patient relapsed, he underwent another round of chemotherapy and was waiting for a bone marrow transplant during his treatment during the course of this case report. For PT intervention, therapeutic exercises were incorporated into play to strengthen his lower extremity strength and muscle endurance. Functional activities were also incorporated into play to improve his aerobic capacity and overall quality of life. Multi-attribute health status classification system (HUI3) utility scores, 6-minute walk test distance (6MWT), lower extremity (LE) strength, transfer and tolerated treatment time were assessed to identify the effect of a PT intervention. OUTCOMES: Despite experiencing fatigue, the patient completed most of the treatments incorporated into play. After 5 weeks of PT intervention, the participant improved on HUI3 (pre: 0.72 and post: 0.92), 6MWT (pre: 156 ft and post: 489 ft), LE strength (squat), transfer (sit to stand) and tolerated treatment time (pre: 16 minutes and post: 44 minutes). DISCUSSION: This case report suggests that incorporating a play-based PT intervention programme could be physically tolerable and functionally beneficial for a young child with relapsed ALL undergoing inpatient chemotherapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892075 TI - Generation and characterization of novel DNA aptamers against coat protein of grouper nervous necrosis virus (GNNV) with antiviral activities and delivery potential in grouper cells. AB - Nervous necrosis virus (NNV) infected larvae and juveniles of more than 50 fish species, resulting in mortality rates of greater than 95%. However, there is no efficient method to control NNV infections. Aptamers generated by selective evolution of ligands by exponential enrichment (SELEX) are short, single-stranded nucleic acid oligomers. They display a high degree of affinity and specificity for many targets, such as viruses and viral proteins. In this study, three novel DNA aptamers (A5, A10, and B11) that specifically target the coat protein (CP) of grouper nervous necrosis virus (GNNV) were selected using SELEX. Secondary structures and minimum free energy (DeltaG) predictions indicated that these aptamers could form stable, secondary stem-loop structures. Electrophoretic mobility shift assays, enzyme-linked immunosorbent assays, Kd measurements, the co-localization of tetramethylrhodamine (TAMRA) labeled-aptamers with the CP and flow cytometry analysis revealed that these aptamers could specifically bind the CP with high (nanomolar) affinities. In addition, competition analysis suggested the aptamers shared some common CP binding sites with the anti-CP antibody. Moreover, all three aptamers did not show any cytotoxic effects in vitro or in vivo, and anti-viral analysis indicated the selected aptamers could inhibit NNV infection in vitro and in vivo. Compared with controls, mortality of GNNV infected fish decreased by 40% and 80% after 10 days infection, when the GNNV was pre-incubated with the 1000 nM A10 and B11, respectively. TAMRA-labeled aptamers could bind to NNV virions and directly enter NNV-infected cells, suggesting they could be used as tracers to study the mechanism of viral infection, as well as for targeted therapy. This is the first time that aptamers targeting a viral protein of marine fish have been generated and characterized. These aptamers hold promise as diagnostic, therapeutic, and targeted drug delivery agents for controlling NNV infections. PMID- 26892074 TI - Does providing written dietary advice improve the ingestion of non-allergic nuts in children with existing nut allergies? - A randomized controlled trial. AB - BACKGROUND: Allergy to one or more nuts is common in children and often complete nut avoidance is advised. More recently, introduction of non-allergic nuts into the diet is advised by some allergists. OBJECTIVE: This study aims to determine whether the provision of additional written dietary advice increases the ingestion of non-allergic nuts by children with nut allergy. Secondary aims include determining which factors facilitate or prevent successful inclusion of non-allergic nuts in the diet, and how inclusion influences quality of life, sensitization and the rate of nut reactions. METHODS: This is a randomized, double-blinded, controlled trial of children with nut allergy who were asked to ingest one or more non-allergic nuts. Participants were 75 children aged 2-16 years (Intervention=36, Control=39), recruited in Adelaide, Australia. Randomized participants were supplied with the intervention (recipe booklet and monthly reminder text messages) or provided standard verbal dietary advice. After 6 months participants were assessed by a blinded investigator with regard to nut ingestion, quality of life, sensitization and nut reactions. RESULTS: The intervention did not increase the ingestion of non-allergic nuts. A negative hospital challenge was a predictor of successful introduction. Parental report of child concern about a reaction was the greatest barrier. Ingestion of non allergic nuts did not improve quality of life or change nut sensitization. Few nut reactions occurred during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of non-allergic nuts by children with nut allergy was not improved by additional dietary intervention. Selective introduction of non-allergic nuts is difficult to achieve when the child is anxious about introduction and challenges cannot be done in a medically supervised setting. CAPSULE SUMMARY: This dietary intervention did not improve non-allergic nut ingestion by nut allergic children. Hospital challenge increased introduction rates, whilst parentally reported child concern about a reaction reduced success. Non-allergic nut ingestion did not change quality of life or sensitization. PMID- 26892078 TI - Discussion. PMID- 26892076 TI - Early outcomes after isolated aortic valve replacement with rapid deployment aortic valve. AB - OBJECTIVE: Minimal access aortic valve replacement is associated with favorable clinical outcomes; however, several meta-analyses have reported significantly longer crossclamp times compared with a full sternotomy. We examined the procedural and early safety outcomes after isolated rapid deployment aortic valve replacement by surgical approach in patients enrolled in the Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve trial. METHODS: The Surgical Treatment of Aortic Stenosis With a Next Generation Surgical Aortic Valve trial was a prospective, multicenter, single-arm study, with successful implants in 287 patients with aortic valve stenosis who underwent rapid deployment aortic valve replacement using the EDWARDS INTUITY Valve System (Edwards Lifesciences, Irvine, Calif). Patients were evaluated perioperatively for procedural times and technical success rates; at discharge, for hospital length of stay; and, at 30 days, for early adverse events. RESULTS: A total of 158 patients underwent isolated aortic valve replacement through a full sternotomy (n = 71), upper hemisternotomy (n = 77), or right anterior thoracotomy (n = 10). Mean age at baseline was 75.7 +/- 7.2 years. Mean aortic crossclamp and cardiopulmonary bypass times (minutes) were similar for full sternotomy and upper hemisternotomy, 43.5 +/- 32.5/71.6 +/- 41.8 and 43.1 +/- 13.1/69.6 +/- 19.1, respectively, and significantly longer for right anterior thoracotomy, 88.3 +/- 18.6/122.2 +/- 22.1 (P < .000). Early adverse event rates were similar, and in hospital mortality rates were low regardless of surgical approach. CONCLUSIONS: These data suggest that isolated rapid deployment aortic valve replacement through an upper hemisternotomy can lead to shorter crossclamp times than has been reported historically in the literature. This may facilitate minimal access aortic valve replacement by eliminating the issue of prolonged crossclamp times. Further, low in-hospital mortality and new permanent pacemaker implant rates were observed regardless of surgical approach. PMID- 26892077 TI - The American Association for Thoracic Surgery Consensus Guidelines: Reasons and purpose. AB - The time interval for the doubling of medical knowledge continues to decline. Physicians, patients, administrators, government officials, and payors are struggling to keep up to date with the waves of new information and to integrate the knowledge into new patient treatment protocols, processes, and metrics. Guidelines, Consensus Guidelines, and Consensus Statements, moderated by seasoned content experts, offer one method to rapidly distribute new information in a timely manner and also guide minimal standards of treatment of clinical care pathways as they are developed as part of bundled care programs. These proposed Consensus Guidelines advance The American Association for Thoracic Surgery's mission of leading in cardiothoracic health care, education, innovation, and modeling excellence. PMID- 26892079 TI - Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. AB - BACKGROUND: The accumulation of soluble oligomeric amyloid-beta peptide (oAbeta) proceeding the formation of senile plaques contributes to synaptic and memory deficits in Alzheimer's disease. Our previous studies have indentified scavenger receptor A (SR-A), especially SR-A type I (SR-AI), as prominent scavenger receptors on mediating oAbeta clearance by microglia while glycan moiety and scavenger receptor cysteine-rich (SRCR) domain may play the critical role. Macrophage receptor with collagenous structure (MARCO), another member of class A superfamily with a highly conserved SRCR domain, may also play the similar role on oAbeta internalization. However, the role of N-glycosylation and SRCR domain of SR-AI and MARCO on oAbeta internalization remains unclear. RESULT: We found that oAbeta internalization was diminished in the cells expressing SR-AI harboring mutations of dual N-glycosylation sites (i.e. N120Q-N143Q and N143Q N184Q) while they were normally surface targeted. Normal oAbeta internalization was observed in 10 SR-AI-SRCR and 4 MARCO-SRCR surface targeted mutants. Alternatively, the SRCR mutants at beta-sheet and alpha-helix and on disulfide bone formation obstructed receptor's N-glycosylation and surface targeting. CONCLUSION: Our study reveals that N-glycan moiety is more critical than SRCR domain for SR-A-mediated oAbeta internalization. PMID- 26892081 TI - No More Debate Over Left Main Stenting Versus Bypass Surgery. PMID- 26892080 TI - Left Main Stenting in Comparison With Surgical Revascularization: 10-Year Outcomes of the (Left Main Coronary Artery Stenting) LE MANS Trial. AB - OBJECTIVES: This study has reported 10-year clinical follow-up of patients enrolled in the prospective, randomized LE MANS (Left Main Stenting) trial. BACKGROUND: The very long-term outcome after left main stenting in comparison with surgical revascularization remains unknown. METHODS: In this prospective, multicenter trial, we randomly assigned 105 patients with unprotected left main coronary artery stenosis with low and medium complexity of coexisting coronary artery disease according to SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score to percutaneous coronary intervention (PCI) with stenting (n = 52) or coronary artery bypass grafting (CABG) (n = 53). Drug-eluting stents were implanted in 35%, whereas arterial grafts to the left anterior descending artery were utilized in 81%. Currently, the mean long-term follow-up was collected at 9.8 +/- 1.0 years. Follow up for all-cause mortality is complete, whereas the incidence of major adverse cardiovascular and cerebral events (MACCE) was reported from 90% of patients. Ambulatory follow-up was completed in 46 (43.9%) patients. RESULTS: At 10 years, there was a trend toward higher ejection fraction in stenting when compared with surgery (54.9 +/- 8.3% vs. 49.8 +/- 10.3%; p = 0.07). The mortality (21.6% vs. 30.2%; p = 0.41) and MACCE (51.1% vs. 64.4%; p = 0.28) were statistically not different between groups; however, numerically the difference was in favor of stenting. Similarly, there was no difference in the occurrence of myocardial infarction (8.7 vs. 10.4%; p = 0.62), stroke (4.3 vs. 6.3%; p = 0.68), and repeated revascularization rates (26.1% vs. 31.3%; p = 0.64). The probability of very long-term survival up to 14 years was comparable between PCI and CABG (74.2% vs. 67.5%; p = 0.34; hazard ratio: 1.45, 95% confidence interval: 0.67 to 3.13); however, there was a trend toward higher MACCE-free survival in the PCI group (34.7% vs. 22.1%; p = 0.06; hazard ratio: 1.71, 95% confidence interval: 0.97 to 2.99). CONCLUSIONS: In patients with unprotected left main coronary artery stenosis with low and medium complexity of coexisting coronary artery disease, stenting offers numerically, but statistically nonsignificant, favorable long term outcome up to 10 years in terms of safety and efficacy outcome measures, therefore, constitutes an alternative therapy for CABG. PMID- 26892083 TI - Newer-Generation Devices for Transcatheter Aortic Valve Replacement: Resolving the Limitations of First-Generation Valves? PMID- 26892085 TI - Transcatheter Aortic Valve Replacement: The Good Results of the New Generation of Transcatheter Aortic Valve Replacement Devices Are Confirmed. PMID- 26892082 TI - Transcatheter Aortic Valve Replacement Using the Repositionable LOTUS Valve: United Kingdom Experience. AB - OBJECTIVES: This study sought to present the U.K. experience to date with the second-generation LOTUS bioprosthesis (Boston Scientific, Natick, Massachusetts). BACKGROUND: First-generation transcatheter aortic valves have limitations. Second generation repositionable valves may improve on some of those limitations. METHODS: Prospectively collected data relating to procedural and in-hospital outcome was analyzed from 10 implantation centers in the United Kingdom. RESULTS: Implants in 228 patients age 81.4 +/- 7.6 years were studied; 53.5% were male. Mean logistic EuroScore was 17.5 +/- 12.4. One hundred eighty-seven (82.0%) were undertaken for aortic stenosis, 7 (3.1%) for aortic regurgitation, and 34 (14.9%) for mixed aortic valve disease. A total of 67.1% of cases were done under local anesthetic and/or sedation with transfemoral access in 94.7% and transaortic in 5.3%. Three device sizes were used: 23 mm (n = 66, 28.9%), 25 mm (n = 39, 17.1%), and 27 mm (n = 123, 53.9%). The valve was successfully deployed in 99.1% of procedures. After implantation, the mean aortic gradient was 11.4 +/- 5.4 mm Hg and aortic valve area 1.6 +/- 0.5 cm(2). In-hospital mortality was 1.8% (n = 4). Complications included cardiac tamponade (1.8%), conversion to sternotomy (1.3%), stroke (3.9%), vascular access-related (7.0%), and acute kidney injury (7.9%). The incidence of moderate/severe aortic regurgitation was 0.8% (n = 2). A total of 31.8% of patients required new permanent pacemaker implantation. CONCLUSIONS: This analysis represents the largest published series on use of the LOTUS valve. Outcomes using this valve are excellent. In-hospital mortality is very low. Complication rates are low, and the LOTUS valve improves on first-generation valves, particularly with regard to residual aortic regurgitation. PMID- 26892084 TI - 1-Year Outcomes With the Fully Repositionable and Retrievable Lotus Transcatheter Aortic Replacement Valve in 120 High-Risk Surgical Patients With Severe Aortic Stenosis: Results of the REPRISE II Study. AB - OBJECTIVES: This analysis presents the first report of 1-year outcomes of the 120 patients enrolled in the REPRISE II (Repositionable Percutaneous Placement of Stenotic Aortic Valve Through Implantation of Lotus Valve System-Evaluation of Safety and Performance) study. BACKGROUND: The fully repositionable and retrievable Lotus Valve (Boston Scientific, Marlborough, Massachusetts) was designed to facilitate accurate positioning, early valve function, and hemodynamic stability during deployment and to minimize paravalvular regurgitation in patients undergoing transcatheter aortic valve replacement. METHODS: The study enrolled 120 symptomatic patients 70 years of age or older at 14 centers in Australia and Europe. Patients had severe calcific aortic stenosis and were deemed to be at high or extreme risk of surgery based on assessment by the heart team. RESULTS: The mean age was 84.4 +/- 5.3 years, 57% (68 of 120) of patients were women, and the mean Society of Thoracic Surgeons score was 7.1 +/- 4.6. The mean baseline aortic valve area was 0.7 +/- 0.2 cm(2), and the mean transvalvular pressure gradient was 46.4 +/- 15.0 mm Hg. All patients were successfully implanted with a Lotus Valve, and 1-year clinical follow-up was available for 99.2% (119 of 120 of patients). The mean 1-year transvalvular aortic pressure gradient was 12.6 +/- 5.7 mm Hg, and the mean valve area was 1.7 +/- 0.5 cm(2). A total of 88.6% patients had no or trivial paravalvular aortic regurgitation at 1 year by independent core lab adjudication, and 97.1% of patients were New York Heart Association functional class I or II. At 1 year, the all-cause mortality rate was 10.9% (13 of 119 patients), disabling stroke rate was 3.4% (4 of 119 patients), disabling bleeding rate was 5.9% (7 of 119 patients), with no repeat procedures for valve-related dysfunction. A total of 31.9% (38 of 119 patients) underwent new permanent pacemaker implantation at 1 year. CONCLUSIONS: At 1 year of follow-up, the Lotus Valve demonstrated excellent valve hemodynamics, no moderate or severe paravalvular regurgitation, and significant and sustained improvement in New York Heart Association functional class status, with good clinical outcomes. (Repositionable Percutaneous Placement of Stenotic Aortic Valve Through Implantation of Lotus Valve System-Evaluation of Safety and Performance [REPRISE II]; NCT01627691). PMID- 26892086 TI - 1-Year Follow-Up Optical Frequency Domain Imaging of Multiple Bioresorbable Vascular Scaffolds for the Treatment of Spontaneous Coronary Artery Dissection. PMID- 26892087 TI - Reply: Microvascular Function in Ischemic Heart Disease: There May Be Room for Improvement. PMID- 26892088 TI - Reply: Microvascular Function in Ischemic Heart Disease: There May Be Room for Improvement. PMID- 26892089 TI - Reply: Microvascular Function in Ischemic Heart Disease: There May Be Room for Improvement. PMID- 26892090 TI - Reply: Low Incidence of Diabetes Mellitus in Coronary Microvascular Dysfunction: An Intriguing Association. PMID- 26892091 TI - Mortality Is Not an Adequate Surrogate for Percutaneous Coronary Intervention Quality. PMID- 26892092 TI - Transcatheter Mitral Valve Implantation in a Patient With an Aortic Mechanical Valve. PMID- 26892093 TI - Hsp90 inhibitor, BIIB021, induces apoptosis and autophagy by regulating mTOR-Ulk1 pathway in imatinib-sensitive and -resistant chronic myeloid leukemia cells. AB - Development of drug resistance due to BCR-ABL point mutations and the persistence of leukemia initiating cells has become a major obstacle for tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML). The BCR-ABL protein is an important client protein of heat shock protein 90 (Hsp90). BIIB021, an orally available Hsp90 inhibitor, has activity against various cancer cells. However, little is known about the inhibitory effect of BIIB021 on CML cells. We evaluated the inhibitory effects of BIIB021 on K562, K562/G (an imatinib resistant cell lines), as well as 32D mouse leukemic cells expressing wild-type BCR-ABL (b3a2, 32Dp210) and T315I mutant BCR-ABL (32Dp210-T315I) cells. Our data showed that BIIB021 induced significant growth inhibition and apoptosis that was predominantly mediated by the mitochondrial pathway. BIIB021 also resulted in proteasomal degradation of BCR-ABL proteins. In addition to induction of apoptosis, we report for the first time that BIIB021 induced autophagic response as evidenced by the formation of autophagosome, increased conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, decreased p62 (SQSTM1) protein levels. Further study suggested that Akt-mTOR-Ulk1 signaling pathway was involved in BIIB021-triggered autophagy. Moreover, blocking autophagy using pharmacological inhibitor 3-methyladenine and bafilomycin A1 significantly enhanced cell death and apoptosis induced by BIIB021, indicating the cytoprotective role of autophagy in BIIB021-treated CML cells. Collectively, these data provide possible molecular mechanisms for the antileukemic effect of BIIB021 on imatinib-sensitive and -resistant CML cells and provide new insights into the future application of BIIB021 in the clinical treatment of CML. PMID- 26892094 TI - Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis. AB - Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses. PMID- 26892096 TI - Editorial: Innovative practice. PMID- 26892095 TI - Apparent mineralocorticoid excess and the long term treatment of genetic hypertension. AB - Apparent mineralocorticoid excess (AME) is a genetic disorder causing severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism owing to deficient 11 beta-hydroxysteroid dehydrogenase type-2 (11betaHSD2) enzyme activity. The 11betaHSD2 enzyme confers mineralocorticoid receptor specificity for aldosterone by converting cortisol to its inactive metabolite, cortisone and inactivating the cortisol-mineralocorticoid receptor complex. The 20year follow-up of a consanguineous Iranian family with three sibs affected with AME shows the successes and pitfalls of medical therapy with spironolactone. The three sibs, (female, male, female) were diagnosed at the ages of 14, 11, and 4 years, respectively. At diagnosis, hypertensive retinopathy and left ventricular hypertrophy were present in the eldest female and retinopathy was noted in the male sib. Spironolactone treatment resulted in decreased blood pressure and rise in serum potassium levels. The older female, age 36, developed reduced left ventricular function with mitral and tricuspid regurgitation and renal failure after her second pregnancy. She was treated with renal transplantation resulting in cure of AME with decreased blood pressure and weaning from antihypertensives. Her younger sibs, age 34 and 26, do not have end organ damage. Early and vigilant treatment improves morbidity in patients with AME. Mineralocorticoid receptor antagonists normalize blood pressure, correct hypokalemia and reduce hypertensive end-organ damage in patients with AME. Low dose dexamethasone can be considered, though the response may be variable. Future directions of therapy include selective mineralocorticoid antagonists. PMID- 26892101 TI - Recent developments in synthetic methods for benzo[b]heteroles. AB - Benzo[b]heteroles containing heteroatoms other than nitrogen and oxygen have received considerable attention for their potential applications in materials science. This poses an increasing demand for efficient, selective, and broad scope methods for their synthesis. This review article summarizes the recent developments in synthetic methods and approaches to access representative members of the benzoheterole family. PMID- 26892099 TI - "Come on Baby. You Know I Love You": African American Women's Experiences of Communication with Male Partners and Disclosure in the Context of Unwanted Sex. AB - We examined African American women's experiences of communication with their male intimate partners a couple of hours before and after an incident of unwanted sex. We also examined women's experiences of disclosure following an incident of unwanted sex. Semi-structured qualitative interviews were conducted with a community-based sample of sexually active African American women (n = 19) reporting at least one incident of sexual coercion (i.e., being pressured into unwanted sex without consent) by an intimate male partner since the age of 18. Our analysis was guided by "the sexual division of power" from Connell's (1987) theory of gender and power. Data were analyzed inductively by examining the interviews for common themes in the following domains: communication before the unwanted sex, communication after the unwanted sex, and disclosure to others. Men pressured partners for unwanted sex through verbal and non-verbal tactics, ranging from pestering and blunt requests for sex to verbal bullying and violence. Many women responded by clearly saying no. However, many women also described eventually ceasing to resist their partners and engaging in unwanted sex. After the unwanted sex, men actively and passively avoided discussing the incident. Although many women discussed the unwanted sex with family and friends, less women disclosed to trained professionals. In some cases, women did not discuss the incident with anyone at all. These findings indicate that, when addressing sexual violence against women, there is a need to target men as well as the norms of masculinity that underpin physical and sexual violence against women. PMID- 26892100 TI - Gender Differences in HIV Sexual Risk Behaviors Among Clients of Substance Use Disorder Treatment Programs in the U.S. AB - This study examined differences in sexual risk behaviors by gender and over time among 1281 patients (777 males and 504 females) from 12 community-based substance use disorder treatment programs throughout the United States participating in CTN 0032, a randomized control trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Zero-inflated negative binomial and negative binomial models were used in the statistical analysis. Results indicated significant reductions in most types of sexual risk behaviors among substance users regardless of the intervention arms. There were also significant gender differences in sexual risk behaviors. Men (compared with women) reported more condomless sex acts with their non-primary partners (IRR = 1.80, 95 % CI 1.21 2.69) and condomless anal sex acts (IRR = 1.74, 95 % CI 1.11-2.72), but fewer condomless sex partners (IRR = 0.87, 95 % CI 0.77-0.99), condomless vaginal sex acts (IRR = 0.83, 95 % CI 0.69-1.00), and condomless sex acts within 2 h of using drugs or alcohol (IRR = 0.70, 95 % CI 0.53-0.90). Gender-specific intervention approaches are called for in substance use disorder treatment. PMID- 26892102 TI - Psychology in Japan. AB - The purpose of this article is to provide information about Japan and its psychology in advance of the 31st International Congress of Psychology (ICP), to be held in Yokohama, Japan, in 2016. The article begins with the introduction of the Japanese Psychological Association (JPA), the hosting organization of the ICP 2016, and the Japanese Union of Psychological Associations consisting of 51 associations/societies, of which the JPA is a member. This is followed by a brief description of a history of psychology of Japan, with emphasis on the variation in our approach to psychology in three different periods, that is, the pre- and post-Pacific War periods, and the post-1960 period. Next, the international contributions of Japanese psychology/psychologists are discussed from the point of view of their visibility. Education and training in psychology in Japanese universities is discussed with a final positive remark about the long-awaited enactment of the Accredited Psychologist Law in September, 2015. PMID- 26892103 TI - Finding of pentastomes of genus Reighardia (Pentastomida) in the Belcher's gull (Larus belcheri). AB - This report describes the finding of Reighardia sp. (Pentastomida) infecting the air sac of two Belcher's gulls (Larus belcheri) found dead on the beaches of Pucusana, a district in southern Lima, Peru. Three pentastomes were collected from two Belcher's gulls. Then, they were morphologically and molecular analyzed. Molecular characterization of the parasite was achieved by amplifying a fragment of the small subunit ribosomal RNA gene (SSU rRNA). Based on both morphological and molecular data the pentastomes were identified as pentastomes of the genus Reighardia. This is the first report showing that the Belcher's gull is a new natural definitive host for this pentastome. PMID- 26892104 TI - In vivo assay of IgE activities on the expulsion of intestinal adult worms. AB - A physiological role of immunoglobulin E (IgE) is to promote parasitic helminth expulsion. This assertion is largely based on a series of studies carried out by Capron's laboratory. They observed that IgE is an essential component of protective immunity against Schistosoma mansoni larvae both in vitro and in vivo. Then, another group reported that IgE-deficient mice show higher worm burdens than wild-type (WT) mice when mice are infected with Trichinella spiralis. Although these studies indicate anti-helminth activities of IgE targeted on larvae forms, they do not prove the fighting effects of IgE on adult worms. In contrast, a recent study demonstrates an expelling activity of IgE for adult worms through an adoptive transfer of immune serum-derived IgE into Strongyloides venezuelensis-infected mice. Here, I describe how IgE is purified from S. venezuelensis-immune sera and is transferred into infected mice to examine its effect on worm expulsion. This method will be used to advance our understanding the mechanism of S. venezuelensis expulsion and explore S. venezuelensis antigens recognized by IgE. Moreover, adoptive transfers of IgE purified from immune sera will be applicable to other helminth infection models to investigate physiological roles of IgE. PMID- 26892105 TI - Circulating Tumor Cells and Tumor Stem Cells Detection in the Peripheral Blood Mononuclear Cells of Breast Cancer. AB - BACKGROUND: Our aim was to retrospectively analyze the relationships between circulating tumor cells (CTCs) and the development of breast cancer, for elucidating the role of CTCs in breast cancer. METHODS: A total of 107 female patients with primary breast cancer and 48 matched healthy female volunteers were recruited. After blood collection, isolation of peripheral blood mononuclear cells (PBMC) was performed followed by the detection of cytokeratin 19 positive (CK19(+) ) and CD44(+) /CD24(-/low) cells, as well as estrogen receptor (ER), progesterone, and CerbB2. Data were analyzed with the SPSS 20.0 software. RESULTS: None of the 48 volunteers were detected with CK19(+) cells in their PBMC, while in 77 patients, 72% of 107 female patients with primary breast cancer, the CK19(+) cells were detected. CK19(+) could also be detected among patients in each grouping by different clinical staging and lymph node metastasis, with statistical differences (all P < 0.05). Further, among the 83 CK19(+) specimens, 32 were also detected with CD44(+) /CD24(-/low) cells. Comparisons of CK19(+) and CD44(+) /CD24(-/low) cells in patients with different clinical features (ER positive vs. ER negative, C-erbB2 positive vs. C-erbB2 negative) and molecular subtypes (triple-negative breast cancer, ER positive, and C-erbB2 positive) showed no obvious difference (all P > 0.05). CONCLUSIONS: Both CTCs and tumor stem cells (TSCs) could be detected in the PBMC of breast cancer patients; besides, positive expression rate of CTCs might be obviously associated with the clinical stage and metastasis. Positive relationship of TSCs and the clinical stage of breast cancer was also proved in this study. PMID- 26892107 TI - Risk Assessment Study of Fluoride Salts: Probability-Impact Matrix of Renal and Hepatic Toxicity Markers. AB - The present risk assessment study of fluoride salts was conducted by oral administration of three different doses of sodium and potassium fluorides (NaF, KF) and zinc fluoride tetrahydrate (ZnF2 *4H2O) to male Wistar rats. The rats were divided into control and nine experimental groups, to which oral injections of 0.5 mL distilled water and 0.5 mL of fluoride solutions, respectively, were given. The dosage of fluoride compounds was adjusted to contain 2.1 mg (low-dose group, LG), 4.3 mg (mid-dose group, MG), and 5.4 mg fluoride per 200 g rat body weight (high-dose group, HG) corresponding to 5, 10, and 12.5 % of LD50 values for NaF. The 24-h urine volume, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine clearance (Ccr) were measured as markers of possible acute renal impact. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined in serum samples as markers of acute hepatic impact. The levels of serum and urinary fluoride were determined to evaluate fluoride bioavailability. The results reveal that higher doses of NaF, KF, and ZnF2 induced renal damage as indicated by higher urinary NAG (p < 0.05 with >=90th percentile of control). High doses of ZnF2 also induced a significant Ccr decrease (p < 0.05 with <=10th percentile of control). Low doses of NaF and mid-doses of ZnF2 induced polyuria (p < 0.05 with >=90th percentile of control) while medium doses of NaF and low doses of KF also induced liver damage, as indicated by a high level of AST (p < 0.05 with >=90th percentile of control). These findings suggest that oral administration of fluoride is a potential, dose dependent risk factor of renal tubular damage. PMID- 26892106 TI - Use of mobile and cordless phones and cognition in Australian primary school children: a prospective cohort study. AB - BACKGROUND: Use of mobile (MP) and cordless phones (CP) is common among young children, but whether the resulting radiofrequency exposure affects development of cognitive skills is not known. Small changes have been found in older children. This study focused on children's exposures to MP and CP and cognitive development. The hypothesis was that children who used these phones would display differences in cognitive function compared to those who did not. METHODS: We recruited 619 fourth-grade students (8-11 years) from 37 schools around Melbourne and Wollongong, Australia. Participants completed a short questionnaire, a computerised cognitive test battery, and the Stroop colour-word test. Parents completed exposure questionnaires on their child's behalf. Analysis used multiple linear regression. The principal exposure-metrics were the total number of reported MP and CP calls weekly categorised into no use ('None'); use less than or equal to the median amount ('Some'); and use more than the median ('More'). The median number of calls/week was 2.5 for MP and 2.0 for CP. RESULTS: MP and CP use for calls was low; and only 5 of 78 comparisons of phone use with cognitive measures were statistically significant. The reaction time to the response inhibition task was slower in those who used an MP 'More' compared to the 'Some' use group and non-users. For CP use, the response time to the Stroop interference task was slower in the 'More' group versus the 'Some' group, and accuracy was worse in visual recognition and episodic memory tasks and the identification task. In an additional exploratory analysis, there was some evidence of a gender effect on mean reaction times. The highest users for both phone types were girls. CONCLUSIONS: Overall, there was little evidence cognitive function was associated with CP and MP use in this age group. Although there was some evidence that effects of MP and CP use on cognition may differ by gender, this needs further exploration. CP results may be more reliable as parents estimated children's phone use and the CPs were at home; results for CP use were broadly consistent with our earlier study of older children. PMID- 26892108 TI - Factors shaping how clinical educators use their educational knowledge and skills in the clinical workplace: a qualitative study. AB - BACKGROUND: In order to consolidate their educational knowledge and skills and develop their educational role, many clinicians undertake professional development in clinical education and supervision. It is well established that these educationally-focussed professional development activities have a positive impact. However, it is less clear what factors within the clinical workplace can shape how health professionals may use and apply their educational knowledge and skills and undertake their educational role. Looking through the lens of workplace affordances, this paper draws attention to the contextual, personal and interactional factors that impact on how clinical educators integrate their educational knowledge and skills into the practice setting, and undertake their educational role. METHODS: Data were gathered via a survey of 387 clinical educators and semi-structured interviews with 12 clinical educators and 6 workplace managers. In this paper, we focus on analysing and reporting the qualitative data gathered in this study. This qualitative data were subject to a thematic analysis and guided by theoretical constructs related to workplace affordances. RESULTS: Three key themes were identified including contextual, personal and interactional factors. Contextual elements referred to organisational structures and systems that impact on participants' educational role, how participants' clinical education role was articulated and configured within the organisation, and how the organisation shaped the educational opportunities available to clinicians. Personal factors encompassed clinicians' personal motivations and goals to teach and be involved in education, develop their own educational skills and function as a role model for students. Interactional factors referred to the professional interactions and networks through which clinicians shared their educational knowledge and skills and further consolidated their profile as educational advocates in their workplace. CONCLUSIONS: There are a number of contextual, personal and interactional factors which interrelate in complex ways and impact on how clinical educators use their educational knowledge and skills and undertake their educational role in the clinical setting. To fully realise the potential of and fulfil the requirements of their educational role, clinical educators need to be provided appropriate experiential and meaningful workplace opportunities and the guidance to use, share and reflect on their educational knowledge and skills in the clinical workplace. PMID- 26892110 TI - National Society Of Genetic Counselors Natalie Weissberger Paul National Leadership Award Address: "Patients and Research: Paths to Personal and Professional Growth". PMID- 26892111 TI - Fyn Plays a Pivotal Role in Fetomaternal Tolerance Through Regulation of Th17 Cells. AB - PROBLEM: Spontaneous abortion is a poorly understood phenomenon, although fetomaternal intolerance is known to play an important role in its pathogenesis. The tyrosine-specific phosphotransferase Fyn has been reported as a significant regulator in immune response. However, its role in fetomaternal immune tolerance and contribution to spontaneous abortion remains unclear. METHODS OF STUDY: Fyn expression was evaluated at the fetomaternal interface of normal pregnant and abortion-prone mice, as well as in decidual tissue obtained from normal human pregnancies and idiopathic miscarriages. A Fyn inhibitor was administrated into the LPS-induced abortion mice to investigate the variation of embryo resorption and local immunity. RESULTS: Fyn expression fluctuated with the progress of normal pregnancy and was elevated in abortion-prone mice and patients with recurrent spontaneous abortion. The Fyn inhibitor reversed LPS-induced embryo absorption and aberrant inflammatory status including redundant expression of IRF4 and increased proportion of Th17 cells. CONCLUSION: Fyn is confirmed as a negative regulator in fetomaternal immune tolerance, through promoting Th17 cell expansion and proinflammatory factors expression. PMID- 26892112 TI - Successful multidisciplinary treatment of refractory cytomegalovirus infection after living donor liver transplantation using mixed lymphocyte reactions: report of a case. AB - A 52-year-old Japanese male underwent ABO-incompatible living donor liver transplantation for acute-on-chronic hepatitis B infection. Fifty-one months later, he became feverish and a cytomegalovirus (CMV) infection was diagnosed. A dramatically high CMV pp65 antigen (C10/C11) load (2,412) was measured, which did not respond to ganciclovir and immune globulin treatment, and increased further to 5,353. The next treatment strategy was the reduction of immunosuppressants, but to simply reduce immunosuppressants can lead to graft loss. Therefore, before using this strategy, responses to alloantigens were evaluated using a carboxyfluorescein-diacetate-succimidyl ester-labeled mixed lymphocyte reaction (CFSE-MLR). Only limited CD4(+) and CD8(+) T-cell proliferation was observed, suggesting the patient was hyporesponsive. After reducing tacrolimus levels from 3-4 ng/mL to <1.5-1.8 ng/mL, the fever dropped immediately and C10/C11 disappeared after 2 months. In conclusion, CFSE-MLR could be a useful tool for the treatment of refractory infectious disease after transplantation and, importantly, for checking a patient's immunosuppressive state beyond the perioperative period. PMID- 26892109 TI - Influence of light alcohol consumption on lifestyle-related diseases: a predictor of fatty liver with liver enzyme elevation in Japanese females with metabolic syndrome. AB - BACKGROUND: Although heavy drinking is known to lead to liver injury, some recent studies have reported that light alcohol consumption (LAC) may play a protective role against fatty liver in the general population, and may even play a protective role against non-alcoholic fatty liver disease (NAFLD) in males with metabolic syndrome (MS). However, the association between LAC and fatty liver with liver enzyme elevation in females with MS is unclear. METHODS: Participants of this study were 20,853 females who underwent a regular health check-up between April 2008 and March 2012 at our hospital. Enrolled subjects were 1141 females with MS, who underwent all necessary tests and drank less than 20 g/day of alcohol. We investigated the presence of fatty liver with liver enzyme elevation, defined in this study as alanine aminotransferase (ALT) levels ?31 IU/I, and the association between LAC and fatty liver with ALT elevation. RESULTS: There was no significant difference in the prevalence of fatty liver and ALT between light drinkers and non-drinkers. The prevalence of individuals receiving a treatment for dyslipidemia and impaired glucose tolerance (IGT) was significantly lower in light drinkers than in non-drinkers. Body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), triglyceride (TG), uric acid (UA), IGT, and visceral fat type MS (V-type MS) were significant predictors of the prevalence of fatty liver with ALT elevation in logistic regression analysis. The odds ratio [OR] (95 % confidence interval [CI], p value) for fatty liver with ALT elevation were as follows: BMI, 2.181 (1.445-3.293, p <0.001); WC, 1.853 (1.280-2.684, p <0.01); DBP, 1.604 (1.120-2.298, p <0.05); TG, 2.202 (1.562-3.105, p <0.001); UA, 2.959 (1.537-5.698, p <0.01); IGT, 1.692 (1.143-2.506, p <0.01); and V-type MS, 3.708 (2.529-5.437, p <0.001). CONCLUSIONS: There was no significant difference in the prevalence of fatty liver with ALT elevation in females with MS between light drinkers and non-drinkers, suggesting that other factors such as BMI, WC, V type MS, and lifestyle-related disease may be more important than LAC for the prevalence of fatty liver with ALT elevation. PMID- 26892113 TI - The effect of animacy on metamemory. AB - Previous research has shown that the animacy quality of materials affects basic cognitive processes such as memory (i.e., animate stimuli are remembered better than are inanimate stimuli). This is referred to as the animacy effect. Little research has examined, however, whether this effect can be extended to higher cognitive processes such as metamemory. In the present studies, we investigated the influence of animacy on judgments of learning (JOLs) and the underlying basis of the animacy effect, namely, processing fluency and beliefs about the animacy effect. In Experiment 1, participants studied animate and inanimate words and made immediate JOLs. Results revealed that participants gave higher estimates for animate than they did for inanimate words. In Experiments 2a and 2b, we evaluated the contribution of processing fluency to the animacy effect either by measuring self-paced study time or by disrupting fluency by presenting half of the words in an easy or difficult font style. Results from both experiments indicated that processing fluency contributes minimally to the animacy effect. In questionnaire based Experiment 3, participants estimated hypothetical participants would better remember the animate words than the inanimate words, suggesting the potential role of beliefs on the animacy effect on JOLs. To conclude, these findings suggest that animacy is a reliable cue when people monitor their learning in higher cognitive processes. The beliefs, not processing fluency, contribute substantially to the animacy effect on JOLs. PMID- 26892115 TI - EuroQol-5 dimensions utility gain according to British and Swedish preference sets in rheumatoid arthritis treated with abatacept, rituximab, tocilizumab, or tumour necrosis factor inhibitors: a prospective cohort study from southern Sweden. AB - BACKGROUND: The development of EuroQol-5 dimensions (EQ-5D) utility over time in rheumatoid arthritis (RA) patients, treated with biologics other than tumour necrosis factor inhibitors (TNFi), based on the standard British (UK) and the new Swedish (SE) EQ-5D preference sets, has not been previously described. METHODS: Demographics, core set data, EQ-5D utility, and treatment characteristics for patients with established RA, receiving biologics in southern Sweden from January 2006 to March 2014, were retrieved from observational databases. Theoretical, UK, and experience-based, SE, EQ-5D mean utilities were plotted over time. RESULTS: Data regarding 2418 treatment courses with abatacept (ABA, n = 100), rituximab (RTX, n = 230), tocilizumab (TOC, n = 121), or TNFi (n = 1967) were included in the analysis. Patients starting TNFi treatment, as expected, had shorter disease duration and less previous biologics. Baseline utilities of patients commencing ABA and TOC, but not RTX, were also lower than in the TNFi group. Following treatment initiation, rapid utility improvements were seen with all therapies, reaching plateaus after approximately 1.5 months, and then remaining fairly stable throughout follow-up in patients adhering to therapy. SE utilities were consistently higher than UK, with baseline values at around 0.7 leaving little room for improvement. CONCLUSIONS: ABA, RTX, TOC, and TNFi treatments were all associated with favourable EQ-5D utility developments in RA patients adhering to therapy. The compression of the experience-based SE preference set towards higher utilities may compromise its ability to detect between-group differences in quality-adjusted life-years, thus making cost-effectiveness harder to demonstrate in cost-utility analyses applying this preference set, rather than the standard UK. PMID- 26892114 TI - Targeted antibiotic delivery using low temperature-sensitive liposomes and magnetic resonance-guided high-intensity focused ultrasound hyperthermia. AB - Chronic non-healing wound infections require long duration antibiotic therapy, and are associated with significant morbidity and health-care costs. Novel approaches for efficient, readily-translatable targeted and localised antimicrobial delivery are needed. The objectives of this study were to 1) develop low temperature-sensitive liposomes (LTSLs) containing an antimicrobial agent (ciprofloxacin) for induced release at mild hyperthermia (~42 degrees C), 2) characterise in vitro ciprofloxacin release, and efficacy against Staphylococcus aureus plankton and biofilms, and 3) determine the feasibility of localised ciprofloxacin delivery in combination with MR-HIFU hyperthermia in a rat model. LTSLs were loaded actively with ciprofloxacin and their efficacy was determined using a disc diffusion method, MBEC biofilm device, and scanning electron microscopy (SEM). Ciprofloxacin release from LTSLs was assessed in a physiological buffer by fluorescence spectroscopy, and in vivo in a rat model using MR-HIFU. Results indicated that < 5% ciprofloxacin was released from the LTSL at body temperature (37 degrees C), while >95% was released at 42 degrees C. Precise hyperthermia exposures in the thigh of rats using MR-HIFU during intravenous (i.v.) administration of the LTSLs resulted in a four fold greater local concentration of ciprofloxacin compared to controls (free ciprofloxacin + MR-HIFU or LTSL alone). The biodistribution of ciprofloxacin in unheated tissues was fairly similar between treatment groups. Triggered release at 42 degrees C from LTSL achieved significantly greater S. aureus killing and induced membrane deformation and changes in biofilm matrix compared to free ciprofloxacin or LTSL at 37 degrees C. This technique has potential as a method to deliver high concentration antimicrobials to chronic wounds. PMID- 26892116 TI - Root-knot nematodes induce pattern-triggered immunity in Arabidopsis thaliana roots. AB - Root-knot nematodes (RKNs; Meloidogyne spp.) are plant parasites with a broad host range causing great losses worldwide. To parasitize their hosts, RKNs establish feeding sites in roots known as giant cells. The majority of work studying plant-RKN interactions in susceptible hosts addresses establishment of the giant cells and there is limited information on the early defense responses. Here we characterized early defense or pattern-triggered immunity (PTI) against RKNs in Arabidopsis thaliana. To address PTI, we evaluated known canonical PTI signaling mutants with RKNs and investigated the expression of PTI marker genes after RKN infection using both quantitative PCR and beta-glucuronidase reporter transgenic lines. We showed that PTI-compromised plants have enhanced susceptibility to RKNs, including the bak1-5 mutant. BAK1 is a common partner of distinct receptors of microbe- and damage-associated molecular patterns. Furthermore, our data indicated that nematode recognition leading to PTI responses involves camalexin and glucosinolate biosynthesis. While the RKN induced glucosinolate biosynthetic pathway was BAK1-dependent, the camalexin biosynthetic pathway was only partially dependent on BAK1. Combined, our results indicate the presence of BAK1-dependent and -independent PTI against RKNs in A. thaliana, suggesting the existence of diverse nematode recognition mechanisms. PMID- 26892117 TI - From the Editor: New drugs, old lessons. PMID- 26892118 TI - JCL roundtable: PCSK9 inhibitors in clinical practice. AB - The roundtable this month will involve a discussion of two new drugs that have been approved by the Food and Drug Administration for the reduction of low density lipoprotein cholesterol (LDL-C). The Food and Drug Administration approved the first of these, alirocumab as an "adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL [low-density lipoprotein]-cholesterol." Evolucumab has similar indications plus an indication specifically for treatment of homozygous familial hypercholesterolemia. This sets the stage for their clinical use and in this roundtable, we will discuss with two experts, the implications of these indications for the practicing physician. Dr McKenney and Dr Moriarty have had extensive experience in the conduct of clinical trials that provided the evidence of safety and efficacy of these so called PCSK9 inhibitors. PMID- 26892119 TI - Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: EXECUTIVE SUMMARY. AB - Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on data published through June 2015. Part 1 of this 2-part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of: (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on cardiovascular disease; and finally (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the executive summary of part 1. PMID- 26892121 TI - Chelation therapy in the treatment of cardiovascular diseases. AB - OBJECTIVE: We examined the effect of chelation therapy on cardiovascular diseases (CVDs). BACKGROUND: EDTA is a chelating agent that binds to metals including calcium and facilitates their excretion. Chelation with EDTA is recommended by some practitioners to treat CVD with the hypothesis that reducing calcium reduces atherosclerotic calcification of arteries. However, chelation therapy has not been approved by the Food and Drug Administration, and its effectiveness is unclear. METHODS: We searched PubMed for English language articles addressing the effect of chelation therapy on CVD events. Articles pertinent to the topic were reviewed in detail. RESULTS: We identified 128 articles addressing the therapeutic value of chelation therapy on CVD; 38 were reviewed in detail including 20 case series and 7 randomized controlled trials. Sixteen case series and 3 randomized controlled trials showed benefit with chelation. The Trial to Assess Chelation Therapy included 1708 post-myocardial infarction patients and demonstrated benefit with chelation therapy, but the Trial to Assess Chelation Therapy investigators concluded that their results did not support the routine use of chelation therapy for post-myocardial infarction patients. CONCLUSIONS: The effectiveness of chelation therapy in reducing recurrent CVD events is unclear, but possible, and warrants additional, carefully designed clinical trials. PMID- 26892120 TI - Lipids and bariatric procedures part 1 of 2: Scientific statement from the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and Obesity Medicine Association: FULL REPORT. AB - Bariatric procedures often improve lipid levels in patients with obesity. This 2 part scientific statement examines the potential lipid benefits of bariatric procedures and represents the contributions from authors representing the National Lipid Association, American Society for Metabolic and Bariatric Surgery, and the Obesity Medicine Association. The foundation for this scientific statement was based on published data through June 2015. Part 1 of this 2 part scientific statement provides an overview of: (1) adipose tissue, cholesterol metabolism, and lipids; (2) bariatric procedures, cholesterol metabolism, and lipids; (3) endocrine factors relevant to lipid influx, synthesis, metabolism, and efflux; (4) immune factors relevant to lipid influx, synthesis, metabolism, and efflux; (5) bariatric procedures, bile acid metabolism, and lipids; and (6) bariatric procedures, intestinal microbiota, and lipids, with specific emphasis on how the alterations in the microbiome by bariatric procedures influence obesity, bile acids, and inflammation, which in turn, may all affect lipid levels. Included in part 2 of this comprehensive scientific statement will be a review of (1) the importance of nutrients (fats, carbohydrates, and proteins) and their absorption on lipid levels; (2) the effects of bariatric procedures on gut hormones and lipid levels; (3) the effects of bariatric procedures on nonlipid cardiovascular disease (CVD) risk factors; (4) the effects of bariatric procedures on lipid levels; (5) effects of bariatric procedures on CVD; and finally, (6) the potential lipid effects of vitamin, mineral, and trace element deficiencies that may occur after bariatric procedures. This document represents the full report of part 1. PMID- 26892122 TI - Assessment of statin therapy, LDL-C levels, and cardiovascular events among high risk patients in the United States. AB - BACKGROUND: Statins have demonstrated significant benefit in reducing cardiovascular disease (CVD) risk. OBJECTIVE: To evaluate statin treatment patterns by intensity, elevated low-density lipoprotein cholesterol (LDL-C) levels, and cardiovascular (CV) events in high-risk CVD patients. METHODS: Patients included were aged >= 18 years, with a coronary heart disease (CHD; Jan 1, 2007-Dec 31, 2011, index date) or CHD risk equivalent (CHD RE) diagnosis (Jan 1, 2007-Dec 31, 2010, index date), in the Truven MarketScan claims database, continuously enrolled for 2 years pre- and up to 1 (CHD) or 2 (CHD RE) years post index. Patients with CHD, CHD RE, rhabdomyolysis, or chronic kidney disease any time pre-index were excluded. Statin therapy was assessed at baseline, 30, 90, and 365 days post-index. LDL-C values were captured in patients with available data at 30-day intervals up to 1 year. CV events were evaluated up to 1 year post index. Descriptive statistics were used to report results. RESULTS: There were 175,103 CHD and 68,290 CHD RE patients; 3333 CHD RE patients had post-index CV events. At 1 year, 38.7% of CHD patients and 44.3% of CHD RE patients with post index CV events were not prescribed statins. Most patients who were prescribed statins, received a moderate-intensity statin. The percentage of patients with LDL-C >= 100 mg/dL reduced over time, but at 1 year, 29.3% of CHD and 30.0% of CHD RE patients with post-index CV events had LDL-C >= 100 mg/dL. At 1 year post index, 9.9% CHD and 7.3% CHD RE patients had at least 1 CV event. CONCLUSION: There is room for better LDL-C management among high-risk CVD patients to reduce their overall CV risk. PMID- 26892124 TI - Cross-sectional associations of plasma fatty acid composition and estimated desaturase and elongase activities with cardiometabolic risk in Finnish children- The PANIC study. AB - BACKGROUND: Knowledge on the association of plasma fatty acid (FA) composition in triacylglycerol (TG) and phospholipid (PL) fractions with cardiometabolic risk in population-based samples of children is lacking. OBJECTIVE: We investigated the associations of proportions of FA in plasma TG and PL fractions as well as estimated desaturase and elongase activities with cardiometabolic risk in a population sample of 384 children aged 6-8 years. METHODS: Plasma FA composition was analyzed by gas chromatography. Desaturase and elongase activities were estimated as product-to-precursor FA ratios. Cardiometabolic risk was assessed using a continuous cardiometabolic risk score (CRS) variable. RESULTS: Higher proportions of myristic and palmitoleic acids in plasma TG and PL were associated with a higher CRS. A lower proportion of linoleic acid in plasma TG was related to a higher CRS. Estimated stearoyl-CoA-desaturase and Delta6-desaturase activities in plasma TG and PL were directly associated with CRS, whereas estimated elongase activity in plasma TG and PL was inversely related to CRS. CONCLUSIONS: Greater proportions of myristic and palmitoleic acids and a smaller proportion of linoleic acid in plasma, as well as higher estimated stearoyl-CoA desaturase and Delta6-desaturase activities and a lower estimated elongase activity, are associated with cardiometabolic risk factors among children. These findings reinforce the evidence that FA metabolism is closely associated with cardiometabolic risk, starting already from childhood. PMID- 26892123 TI - Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. AB - BACKGROUND: Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG). OBJECTIVE: Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function. METHODS: We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (>= 20-30 ng/mL), and optimal (>= 30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression. RESULTS: In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group. CONCLUSION: Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG. Future trials examining vitamin D supplementation and cardiovascular disease risk should consider using changes in an extended lipid panel as an additional outcome measurement. PMID- 26892125 TI - Novel mutations in the GPIHBP1 gene identified in 2 patients with recurrent acute pancreatitis. AB - BACKGROUND: Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) has been demonstrated to be essential for the in vivo function of lipoprotein lipase (LPL), the major triglyceride (TG)-hydrolyzing enzyme involved in the intravascular lipolysis of TG-rich lipoproteins. Recently, loss-of-function mutations of GPIHBP1 have been reported as the cause of type I hyperlipoproteinemia in several patients. METHODS: Two unrelated patients were referred to our Lipid Units because of a severe hypertriglyceridemia and recurrent pancreatitis. We measured LPL activity in postheparin plasma and serum ApoCII and sequenced LPL, APOC2, and GPIHBP1. RESULTS: The 2 patients exhibited very low LPL activity not associated with mutations in LPL gene or with ApoCII deficiency. The sequence of GPIHBP1 revealed 2 novel point mutations. One patient (proband 1) was found to be homozygous for a C>A transversion in exon 3 resulting in the conversion of threonine to lysine at position 80 (p.Thr80Lys). The other patient (proband 2) was found to be homozygous for a G>T transversion in the third base of the ATG translation initiation codon in exon 1, resulting in the conversion of methionine to isoleucine (p.Met1Ile). CONCLUSION: In conclusion, we have identified 2 novel GPIHBP1 missense mutations in 2 unrelated patients as the cause of their severe hypertriglyceridemia. PMID- 26892127 TI - Variability of triglyceride levels and incidence of microalbuminuria in type 2 diabetes. AB - BACKGROUND: Experimental and clinical studies have shown a strong association between hypertriglyceridemia and diabetic nephropathy. A variability of triglyceride (TG) levels has been reported in diabetes. OBJECTIVES: To investigate the relationship of TG variability with the incidence of microalbuminuria (albumin excretion rate > 20 MUg/min), in patients with type 2 diabetes. METHODS: A longitudinal, retrospective, observational study was performed on a consecutive series of 457 normoalbuminuric outpatients, with measurements of HbA1c, lipids and microalbuminuria thrice per year with 6.8-year follow-up. TG variability, defined as standard deviation of TG (TG-SD) and TG-SD adjusted for the number of visits was calculated. A nested case-control sensitivity analysis was performed to validate the results of the primary cohort study. RESULTS: Incident microalbuminuria (N = 124, 27.1%) was associated with higher median TG-SD (33.6 mg/dL vs 29.0 mg/dL, P < .05) and TG-SD adjusted for the number of visits (31.4 mg/dL vs 26.7 mg/dL, P < .05). At multivariate (Cox) analysis, logTG-SD and adj-logTG-SD were significant predictors of incident microalbuminuria (hazard ratio 2.1 [1.1-4.2], P = .028 and 1.5 [1.1-3.3], P = .042, respectively). In the case-control analysis, time spent with TG > 150 mg/dL during the follow-up was significantly higher in cases vs controls (27.2 +/- 19 vs 16.7 +/- 12.5 months, P < .05) with hazard ratio 2.0 (1.1-5.1), P < .05, for adj-logTG-SD. CONCLUSIONS: A higher intraindividual TG variability is a predictor of incident microalbuminuria in type 2 diabetes. In addition, time of exposure to elevated TG levels (>150 mg/dL) predicts incident microalbuminuria. PMID- 26892126 TI - Premature coronary heart disease and autosomal dominant hypercholesterolemia: Increased risk in women with LDLR mutations. AB - BACKGROUND: For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations. OBJECTIVE: This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex. METHODS: Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH. RESULTS: Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42 8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile. CONCLUSIONS: Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers. PMID- 26892128 TI - Inverse relationship between high-density lipoprotein cholesterol raising and high-sensitivity C-reactive protein reduction in older patients treated with lipid-lowering therapy. AB - BACKGROUND: Little is known regarding relationships between high-sensitivity C reactive protein (hsCRP) and lipoproteins other than low-density lipoprotein cholesterol (LDL-C). High-density lipoprotein (HDL), with both anti-inflammatory and cholesterol-mediating effects, is of particular interest. This exploratory analysis assessed associations between hsCRP and lipids in older (>65 years) patients with moderate and/or high cardiovascular disease risk, before and after treatment with ezetimibe/simvastatin (E/S) or atorvastatin (ATV). METHODS: An analysis of a multicenter, randomized, double-blind, 12-week study. Correlations were assessed in 1054 patients with both baseline and 12-week hsCRP <= 10 mg/L, pooled across doses of E/S (10/20 and 10/40 mg) and ATV (10, 20, and 40 mg), and combined E/S + ATV treatments. Because of multiple comparisons, observed relationships were considered significant only if P values were < .01. RESULTS: Correlations between baseline levels of hsCRP and either LDL-C, non-HDL-C, or apolipoprotein B were weak and nonsignificant in the E/S, ATV, and E/S + ATV groups. After 12 weeks of treatment, these correlations increased slightly and significantly in all groups, except for LDL-C in the ATV group. HDL-C was significantly but inversely correlated with hsCRP in the ATV and E/S + ATV groups at baseline, and in all groups at 12 weeks. Only with HDL-C did change correlate with change in hsCRP in both the E/S and combined groups. CONCLUSIONS: Relationships between hsCRP and lipid factors in older patients were weak at baseline and somewhat stronger after treatment. HDL-C was inversely and consistently correlated with baseline and 12-week on-treatment hsCRP and with therapy-induced changes in HDL-C and hsCRP. PMID- 26892129 TI - Small, dense high-density lipoprotein 3 particles exhibit defective antioxidative and anti-inflammatory function in familial hypercholesterolemia: Partial correction by low-density lipoprotein apheresis. AB - BACKGROUND: Familial hypercholesterolemia (FH) features elevated oxidative stress and accelerated atherosclerosis driven by elevated levels of atherogenic lipoproteins relative to subnormal levels of atheroprotective high-density lipoprotein (HDL). Small, dense HDL3 potently protects low-density lipoprotein (LDL) against proinflammatory oxidative damage. OBJECTIVE: To determine whether antioxidative and/or anti-inflammatory activities of HDL are defective in FH and whether such defects are corrected by LDL apheresis. METHODS: Antioxidative and antiinflammatory activities of HDL were evaluated as protection of reference LDL from oxidative stress and capacity to prevent accumulation of proinflammatory oxidised lipids, respectively. Lipid surface rigidity of HDL was assessed using a fluorescent probe. HDL components were measured by analytical approaches. Systemic oxidative stress was characterized as plasma 8-isoprostanes. RESULTS: Pre-LDL-apheresis, FH patients (n = 10) exhibited elevated systemic oxidative stress (3.3-fold, P < 0.001) vs. sex- and age-matched normolipidemic controls (n = 10). Both antioxidative and antiinflammatory activity of HDL3 were impaired (up to -91%, P < 0.01) in FH. Sphingomyelin and saturated fatty acid contents were elevated in FH HDL3, resulting in enhanced lipid surface rigidity. The surface lipid content (phospholipids, free cholesterol) was reduced in FH (up to -15%, P < 0.001), whereas content of core lipids (cholesteryl esters, triglycerides) was elevated (up to +17%, P < 0.001). Molar apolipoprotein A-I content of HDL3 was subnormal in FH. A single LDL-apheresis session partially corrected (by up to 76%) deficient HDL antiatherogenic activities, attenuated systemic oxidative stress and partially normalised both the lipid composition and surface rigidity of HDL particles. CONCLUSIONS: FH features elevated oxidative stress and deficient antioxidative and anti-inflammatory activities of small, dense HDL3; such functional deficiency is intimately linked to anomalies in lipid and protein composition, which may impair the capacity of HDL to acquire and inactivate oxidized lipids. PMID- 26892130 TI - Patterns of statin use and cholesterol goal attainment in a high-risk cardiovascular population: A retrospective study of primary care electronic medical records. AB - OBJECTIVE: To describe real-life patterns of statin use and cholesterol goal attainment in a retrospective cohort of patients with high cardiovascular risk. METHODS: Retrospective cohort study of 21,636 individuals, 18.34% women, mean age 63.30 years (standard deviation 6.29). New statin users aged 35 to 74 years at high cardiovascular risk and with no previous cardiovascular disease in primary care electronic medical records (2006-2011). Patterns of statin use were based on statin type, potency, and 1-year statin switches. OUTCOMES: Relative mean reductions over 1 year and probability of goal attainment (<3.3 mmol/L). Natural patterns of statin use were identified using multiple correspondence analysis; general linear and logistic models were used to estimate low-density lipoprotein cholesterol (LDL-C) reductions and goal attainment probability. RESULTS: Three patterns of statin use were defined: low (3.82% of the population), moderate (71.94%), and high intensity (24.24%). After 1 year, potency decreased 42.74%, 64.16%, and 50.94%, respectively, and 37.41%, 29.47%, and 30.16% of the population stopped taking statins in low, moderate, and high patterns, respectively. Relative reductions in LDL-C: low intensity, 15.7% (95% confidence interval [CI]: -22.96 to 54.36); moderate intensity, 29.72% (95% CI: 29.12 30.32); and high intensity, 24.20% (95% CI: -8.08 to 40.32). There was a direct relationship between higher intensity patterns and greater probability of goal attainment. CONCLUSIONS: Three real-life patterns of statin use were identified. Lipid management strategies in primary care should focus on improving adherence to treatment. People starting at low potency should switch to a moderate pattern; more intensive therapies should be considered in who require a larger LDL-C reduction to reach therapeutic targets, patients with good treatment adherence who do not achieve the goal with a moderate pattern of therapy or patients at very high risk. PMID- 26892131 TI - Comparison between European and Iranian cutoff points of triglyceride/high density lipoprotein cholesterol concentrations in predicting cardiovascular disease outcomes. AB - BACKGROUND: High triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) are important cardiovascular risk factors. The exact prognostic value of the TG/HDL-C ratio, a marker for cardiovascular events, is currently unknown among Iranians so this study sought to determine the optimal cutoff point for the TG/HDL-C ratio in predicting cardiovascular disease events in the Iranian population. METHOD: The Isfahan Cohort Study (ICS) is an ongoing, longitudinal, population-based study that was originally conducted on adults aged >= 35 years, living in urban and rural areas of three districts in central Iran. After 10 years of follow-up, 5431 participants were re-evaluated using a standard protocol similar to the one used for baseline. At both measurements, participants underwent medical interviews, physical examinations, and fasting blood measurements. "High-risk" subjects were defined by the discrimination power of indices, which were assessed using receiver operating characteristic (ROC) analysis; the optimal cutoff point value for each index was then derived. RESULTS: The mean age of the participants was 50.7 +/- 11.6 years. The TG/HDL-C ratio, at a threshold of 3.68, was used to screen for cardiovascular events among the study population. Subjects were divided into two groups ("low" and "high" risk) according to the TG/HDL-C concentration ratio at baseline. A slightly higher number of high-risk individuals were identified using the European cutoff points of 63.7% in comparison with the ICS cutoff points of 49.5%. The unadjusted hazard ratio (HR) was greatest in high-risk individuals identified by the ICS cutoff points (HR = 1.54, 95% CI [1.33-1.79]) vs European cutoff points (HR = 1.38, 95% [1.17-1.63]). There were no remarkable changes after adjusting for differences in sex and age (HR = 1.58, 95% CI [1.36-1.84] vs HR = 1.44, 95% CI [1.22-1.71]) for the ICS and European cutoff points, respectively. CONCLUSION: The threshold of TG/HDL >= 3.68 is the optimal cutoff point for predicting cardiovascular events in Iranian individuals. PMID- 26892133 TI - Impact of avocado-enriched diets on plasma lipoproteins: A meta-analysis. AB - BACKGROUND: Optimizing plasma lipoproteins is the primary goal of pharmacotherapy and diet interventions in people at risk for cardiovascular diseases. Avocados offer a rich source of monounsaturated fat and may pose beneficial effects on the lipid profile. OBJECTIVE: We aimed to perform a meta-analysis of randomized clinical trials assessing the impact of avocados on TC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and/or triglycerides (TG). METHODS: We searched PUBMED, Cumulative Index to Nursing and Allied Health Literature, Index to Nursing and Allied Health Literature, and the Cochrane Database of Systemic Reviews from their inception to February 2015. The weighted mean difference from baseline was calculated for all endpoints. Subgroup analyses were performed to assess heterogeneity, and funnel plots inspected to assess publication bias. RESULTS: Ten unique studies (n = 229) were included. Avocado consumption significantly reduced TC, LDL-C, and TG by -18.80 mg/dL (95% confidence interval [CI], -24.56 to -13.05; I(2), 46.9%), -16.50 mg/dL (95% CI, 22.91 to -10.10; I(2), 72.5%), -27.20 mg/dL (95% CI, -44.41 to -9.99; I(2), 91.1%) respectively. High-density lipoprotein cholesterol decreased nonsignificantly by -0.18 mg/dL (95% CI, -3.23 to 2.88; I(2), 84.8%). CONCLUSION: Avocado-substituted diets significantly decrease TC, LDL-C, and TG levels. Substituting dietary fats with avocados versus adding to the free diet should be the primary recommendation strategy. Larger trials looking at the impact of avocados on major adverse cardiovascular events are warranted. PMID- 26892132 TI - Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China. AB - OBJECTIVE: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. MATERIALS AND METHODS: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. RESULTS: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. CONCLUSION: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients. PMID- 26892135 TI - Icosabutate for the treatment of very high triglycerides: A placebo-controlled, randomized, double-blind, 12-week clinical trial. AB - BACKGROUND: Icosabutate is a structurally enhanced omega-3 fatty acid molecule developed with the aim of achieving improved triglyceride (TG)-lowering efficacy, increased potency, and preserved safety compared with conventional prescription omega-3 fatty acid. OBJECTIVE: To evaluate the efficacy and safety of icosabutate 600 mg once daily in patients with very high TGs. METHODS: After a 6-8 week run in period, men and women with TG levels >= 500 mg/dL and <= 1500 mg/dL were randomized to double-blind treatment with placebo or icosabutate 600 mg for 12 weeks. The primary end point was % change from baseline in TGs at 12 weeks. RESULTS: A total of 87 subjects were randomized. At baseline, median TG (interquartile range) levels were 611 (543-878) and 688 (596-892) mg/dL, and the median change after 12 weeks of treatment was -51% and -17%, respectively, for a placebo-corrected change of -33% (P < .001). Adjusted for placebo, icosabutate significantly reduced very low-density lipoprotein cholesterol (-36%, P < .001), remnant lipoprotein cholesterol (-34%, P < .001), apolipoprotein (Apo) C-III ( 35%, P < .001), trended toward reduced non-high-density lipoprotein cholesterol ( 7%, P = .064); significantly increased high-density lipoprotein cholesterol (18%, P < .001) and low-density lipoprotein cholesterol (28%, P < .001), with a trend of an increased lipoprotein (a; 10%, P = .054). No changes were observed in total cholesterol, apolipoprotein B, or apolipoprotein A1. Fasting plasma glucose was unchanged, whereas fasting plasma insulin was reduced (P = .001) with icosabutate. Icosabutate was generally well tolerated. CONCLUSION: Treatment with icosabutate once daily significantly reduced TG, very low-density lipoprotein cholesterol, and Apo C-III levels in patients with very high TG levels. This trial was registered at www.clinicaltrials.gov as NCT01893515. PMID- 26892136 TI - Increased statin eligibility based on ACC/AHA versus NCEP guidelines for high cholesterol management in Chile. AB - BACKGROUND: In 2013, the American College of Cardiology and the American Heart Association (ACC/AHA) jointly released new guidelines for cardiovascular risk assessment and cholesterol management that substantially modified the previous recommendations proposed by the National Cholesterol Education Program (NCEP) in 2001. The relative impact of these new guidelines on potential statin use has not been estimated in Latin American populations. OBJECTIVE: To estimate and compare eligibility for statin therapy based on ACC/AHA and NCEP guidelines in adult Chilean population. METHODS: Using data from the last National Health Survey (2009-2010 NHS), we conducted a cross-sectional analysis in a representative sample of the Chilean adult population and calculated the proportion of individuals that would receive statins under each set of guidelines. RESULTS: According to ACC/AHA guidelines, the population eligible for statin treatment increased from 21.7% (NCEP guidelines) to 33.2% (overall 53% increase). This effect was more pronounced among women (29.6% under ACC/AHA vs 15.6% under NCEP) and with those of advanced age (75% of the subjects >60 years of age compared with 46% under NCEP). The newly eligible group included more women and older subjects and individuals with lower LDL cholesterol levels. CONCLUSION: Compared with NCEP recommendations, the new ACC/AHA guidelines significantly increased the number of Chilean adults eligible for statin therapy. Full implementation of the new recommendations may have important public health implications in Chile and other Latin American countries, as more women and older subjects without cardiovascular disease would qualify for statin treatment. PMID- 26892138 TI - Two novel mutations in the ABCG5 gene, c.144 -1G>A and c.1523 delC, in a Mexican family with sitosterolemia. AB - Sitosterolemia is a disease characterized by an intestinal hyperabsorption of plant sterols and cholesterol. Affected individuals have mutations in both alleles of either ABCG5 or ABCG8 genes, leading to a total loss of one of the proteins and subsequent functional deficiency. We here report a Mexican family with clinical and biochemical features of sitosterolemia carrying 2 new mutations of the ABCG5 gene. Concentrations of sitosterol, campesterol, and cholesterol were found to be higher for the index case (a 10-year-old girl) than for her also affected sibling (64.1 vs 19 mg/dL, 32 vs 12.1 mg/dL, and cholesterol 295 vs 235 mg/dL, respectively). Both individuals showed 2 new ABCG5 gene mutations identified by sequencing, which is concordant with their biochemical diagnosis of sitosterolemia. The first mutation was a c.144 -1G>A transition that disrupts the intron 1 splicing acceptor site. The second mutation is the deletion c.1523 delC, which occurred in exon 11, causing an amino acid change at codon 510 (p.His510Thr) and a stop codon at codon 511 (p.Leu511X). The father is heterozygote for the mutation c.144 -1G>A, whereas the mother is heterozygote for the mutation c.1523 delC. In conclusion, we here report the first case of a Mexican family with sitosterolemia carrying two new ABCG5 gene mutations. PMID- 26892134 TI - Serum level of LOX-1 ligand containing ApoB is associated with increased carotid intima-media thickness in Japanese community-dwelling men, especially those with hypercholesterolemia LOX-1 ligand and IMT in Japanese. AB - BACKGROUND: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than usual lipid parameters; however, the relationship between LAB and carotid intima-media thickness (IMT) was not clear even in Asian populations. METHODS: A total of 992 community-dwelling Japanese men, aged 40 to 79 years, were enrolled in the present study. Serum LAB levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody. RESULTS: Serum LAB levels (median [interquartile range], MUg cs/L) were 5341 MUg cs/L (4093-7125). The mean average IMT of the common carotid artery was highest in the fourth LAB quartile (842 MUm) compared with the first quartile (797 MUm) after adjustment for age, high-density lipoprotein cholesterol, triglyceride, body mass index, hypertension, diabetes, high sensitivity C-reactive protein, smoking, and alcohol drinking. However, this statistically significant difference was lost after further adjustment for total cholesterol (TC). After stratification using the combination of median LAB and hypercholesterolemia (serum TC >= 6.21 mmol/L and/or lipid-lowering medication), the adjusted mean average IMT (standard error) in the high LAB/hypercholesterolemia group was 886 MUm (12.7), 856 MUm (16.7) in the low LAB/hypercholesterolemia group, and 833 MUm (8.4) in the low LAB/normal cholesterol group (P = .004). After further adjustment for TC, mean average IMT in the high LAB group was significantly higher than that measured in the low LAB group in hypercholesterolemic participants not taking lipid-lowering medication. CONCLUSION: Serum LAB was associated with an increased carotid IMT in Japanese men, especially those with hypercholesterolemia. PMID- 26892137 TI - A Chinese patient with recurrent pancreatitis during pregnancy induced by hypertriglyceridemia associated with compound heterozygosity (Glu242Lys and Leu252VaL) in the lipoprotein lipase gene. AB - We herein report a novel compound heterozygote of Glu242Lys and Leu252Val in a Chinese patient, characterized by recurrent hypertriglyceridemia-induced acute pancreatitis caused by lipoprotein lipase deficiency. The proband's LPL level after injection of heparin was measured at 184 U/L, considerably lower than the normal controls (382 U/L). Furthermore, LPL activity in the proband was 16.7% of the normal controls. However, the hepatic lipase activity was 80% of the normal controls. These results indicated that the compound mutation was associated with hypertriglyceridemia due to both LPL deficiency and defective LPL function. The LPL deficiency was partially compensated by the roughly normal hepatic lipase, resulting in the apparent normal phenotype of the proband until pregnancy. PMID- 26892139 TI - Comment on the article by Moriarty et al. PMID- 26892140 TI - Authors' reply: Comment on: High stop-bang questionnaire scores predict intraoperative and early postoperative adverse events. PMID- 26892141 TI - Natural products discovery needs improved taxonomic and geographic information. AB - Covering: up to 2016Marine and terrestrial organisms yield a remarkable chemical diversity and are important sources for discovery of new chemical products. In order to maximize the bioprospecting efficiency of natural products (NP), taxonomy, geography and biodiversity are starting to be used to draw conclusions on which taxonomic groups and/or regions may be of interest for future research. However, accurate taxonomic information and sampling location of source organisms have often been overlooked. Although these issues were already reported a few decades ago and improvements have been made, such outstanding problems are still recurrent in recent peer-reviewed literature. Here, we focus on the importance of taxonomic and geographic identification of source material and illustrate how taxonomic and geographic data of source organisms continues to be poorly handled. It is our opinion that this issue needs to be discussed within the NP community with the ultimate goal of improving publication standards and guaranteeing the scientific principle of research reproducibility. Moreover, by doing so, it will be possible to take advantage of information available in the literature to develop cross-disciplinary meta-analyses that may help to advance the state of the art of NP research and future bioprospecting endeavours. PMID- 26892143 TI - Long-term results after artificial iris implantation in patients with aniridia. AB - BACKGROUND: The custom-made, flexible artificial iris developed by HumanOptics and Koch can reconstruct the anterior segment of patients with aniridia. The aim of this study was to evaluate the long-term clinical outcome and complication spectrum after artificial iris implantation and the role of the embedded fiber mesh in view of specific complications. METHODS: In this retrospective interventional case series, patients received an artificial iris between 2004 and 2013. Only eyes with a minimum follow-up period of 2 years were included. Indications were congenital, traumatic, or iatrogenic aniridia. The artificial iris was used either with or without embedded fiber mesh for partial or full prostheses. RESULTS: We included 34 patients (mean age 48.8 years; SD +/-17.2) with a mean follow-up of 50.0 months (SD +/-18.9 months). No repositioning of prostheses was necessary. In cases of keratopathy (17.6 %) visual function increased from baseline mean 1.6 logMAR (SD +/-0.7) to 1.2 logMAR (SD +/-0.7) after artificial iris implantation. The remaining iris tissue darkened during the follow-up in 23.5 % (83.3 % with and 10.7 % without mesh), 8.8 % developed glaucoma (50 % with and 0 % without mesh) and 14.7 % needed consecutive surgery after prostheses implantation (50 % with and 7.1 % without mesh). In three out of seven trauma cases (42.9 %) silicone oil was spilled into the anterior chamber after 2.5 years on average. CONCLUSION: The artificial iris prosthesis revealed a good clinical outcome in terms of long-term stability, cosmetic appearance, visual function, and represents a good functional iris diaphragm for compartmentalisation. Complications such as glaucoma, darkening of iris tissue, and need for consecutive anterior segment surgery are clearly associated with implants with integrated fiber mesh, but not to those without. Hence, the use of full iris prostheses without embedded fiber mesh, even in cases with remnant iris, and the use of slightly smaller implants than officially recommended may be beneficial. PMID- 26892142 TI - Purity matters: A workflow for the valid high-resolution lipid profiling of mitochondria from cell culture samples. AB - Subcellular lipidomics is a novel field of research that requires the careful combination of several pre-analytical and analytical steps. To define a reliable strategy for mitochondrial lipid profiling, we performed a systematic comparison of different mitochondria isolation procedures by western blot analyses and comprehensive high-resolution lipidomics. Using liver-derived HepG2 cells, we compared three common mitochondria isolation methods, differential centrifugation (DC), ultracentrifugation (UC) and a magnetic bead-assisted method (MACS). In total, 397 lipid species, including 32 cardiolipins, could be quantified in only 100 MUg (by protein) of purified mitochondria. Mitochondria isolated by UC showed the highest enrichment in the mitochondria-specific cardiolipins as well as their precursors, phosphatidylglycerols. Mitochondrial fractions obtained by the commonly used DC and the more recent MACS method contained substantial contaminations by other organelles. Employing these isolation methods when performing lipidomics analyses from cell culture mitochondria may lead to inaccurate results. To conclude, we present a protocol how to obtain reliable mitochondria-specific lipid profiles from cell culture samples and show that quality controls are indispensable when performing mitochondria lipidomics. PMID- 26892144 TI - Emerging surgical treatments for renal cell carcinoma. AB - Treatment of renal cell carcinoma has evolved considerably over the last few years. While total nephrectomy is necessary at times, nephron-sparing surgery, with a goal of renal function preservation, should always be considered. Although open partial nephrectomy is considered the gold standard approach for nephron sparing surgery, laparoscopic- or robotic-assisted techniques allow urologists to perform renal surgery less invasively, with excellent long-term oncological outcomes. Cryotherapy and radiofrequency ablation are less invasive management approaches for carefully selected patients with small renal masses. Active surveillance should be considered in elderly or patients who are unfit for surgery. Ultimately, the method chosen for management of a renal mass is an informed decision made by the physician and patient. PMID- 26892145 TI - Hypoxic conditioned medium of placenta-derived mesenchymal stem cells protects against scar formation. AB - AIMS: Scar formation after wound repair affects people's daily life. Mesenchymal stem cells were reported to have a beneficial role in attenuating the scar formation. In the present study, placenta-derived mesenchymal stem cells (PMSCs) were isolated and the effects of hypoxic conditioned medium of PMSCs on scar formation were explored. MAIN METHODS: To evaluate the effect of hypoxia on PMSCs, proliferation of PMSCs was detected by trypan blue staining and the HIF 1alpha level was detected by western blot. Then in vivo scar formation assay was performed and the histopathologic changes were evaluated by HE staining and levels of TGF-beta1 and collagen I were detected by quantitative real-time PCR. The IL-10 level was detected by ELISA and then migration of HFF-1 cells was detected by wound healing assay after treatment with IL-10 or IL-10 antibody. KEY FINDINGS: Our study showed that hypoxic conditioned medium of PMSCs reduced scar formation in vivo and inhibited the proliferation and migration of skin fibroblasts in vitro. Further mechanism study showed that, the level of IL-10 was affected by hypoxia, treatment with IL-10 mimicked the function of hypoxic conditioned medium of PMSCs and inhibition of IL-10 reversed the protective role of hypoxic conditioned medium of PMSCs. Thus, hypoxic conditioned medium of PMSCs may perform the protective role against scar formation through IL-10. SIGNIFICANCE: Our study reveals a possible mechanism of the protective effect of PMSCs against scar formation and provides evidence for the hypothesis that PMSCs may be a promising therapy for the treatment of wounds. PMID- 26892146 TI - Exercise training activates neuregulin 1/ErbB signaling and promotes cardiac repair in a rat myocardial infarction model. AB - AIMS: Exercise training (ET) has a cardioprotective effect and can alter the molecular response to myocardial infarction (MI). The Neuregulin 1 (NRG1)/ErbB signaling plays a critical role in cardiac repair and regeneration in the failing heart. We sought to investigate whether ET following MI could activate the NRG1/ErbB signaling and promote cardiac repair and regeneration. MAIN METHODS: Male Sprague-Dawley rats were used to establish the MI model. Exercise-trained animals were subjected to four weeks of exercise (16m/min, 50min/d, 5d/wk) following the surgery. AG1478 was used as an inhibitor of ErbB (1mg/kg body weight, administered i.v. every other day during the process of training). NRG1/ErbB signaling activation, cardiomyocyte (CM) proliferation and apoptosis were evaluated. KEY FINDINGS: In the exercise-trained rats, NRG1 expression was up-regulated and ErbB/PI3K/Akt signaling was activated compared with the MI group. In addition, ET preserved heart function accompanied with increased numbers of BrdU(+) CMs, PCNA(+) CMs and c-kit(+) cells, and reduced apoptosis level in the MI rats. In contrast, blocking ErbB signaling by AG1478 attenuated the ET-induced cardiac repair and regeneration. SIGNIFICANCE: ET up-regulates NRG1 expression and activates ErbB2, ErbB4 and PI3K/Akt signal transduction to promote cardiac repair through endogenous regeneration. Activation of ErbB may be an underlying mechanism for the ET-induced cardiac repair and regeneration following MI. PMID- 26892147 TI - Arsenic trioxide augments all-trans retinoic acid-induced differentiation of HL 60 cells. AB - AIMS: All-trans retinoic acid (ATRA) is used to treat patients with acute promyelocytic leukemia (APL) due to its ability to resume the differentiation of APL cells. Recently, clinical trials have been started to evaluate ATRA plus arsenic trioxide (ATO) as a combination treatment for APL patients. However, little is known about the detailed mechanisms underlying its efficacy. We therefore investigated the effects of this combination on the differentiation and differentiation-related gene expression. MAIN METHODS: Human leukemia HL-60 cells differentiation was examined using nitro blue tetrazolium and CD11b. The levels of mRNA and protein were determined by RT-qPCR, microarray, western blot and ELISA, respectively. The promoter activity was assessed by luciferase activity. The arsenic concentration was determined by ICP-MS. KEY FINDINGS: ATRA-induced HL 60 differentiation was augmented by co-treatment with ATO. A microarray analysis showed that ATRA plus ATO treatment markedly down-regulated the expression of proteinase 3 (PRTN3), which is involved in the differentiation arrest of leukemia cells, compared with treatment with ATRA alone. The PRTN3 mRNA level was suppressed by treatment with ATRA alone, and then further suppressed by co treatment with ATO, accompanied by a concomitant increase in Sp1 protein, which is known to facilitate differentiation. The expression levels of azurocidin, telomerase reverse transcriptase, ferritin, and interleukin-1beta were also altered by co-treatment with ATO. SIGNIFICANCE: Co-treatment with ATO enhances ATRA-induced HL-60 differentiation by altering the expression of genes involved in cell differentiation, providing the molecular basis for a combination therapy using ATO plus ATRA to treat leukemia patients. PMID- 26892148 TI - JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice. AB - AIM: To assess the beneficial effects of JiangTang XiaoKe (JTXK) granule on the bone metabolism in high fat diet (HFD) fed KK-Ay diabetic mice. MATERIALS AND METHODS: The KK-Ay mice were used as a diabetic model, while C57BL/6 mice were utilized as the non-diabetic control. The left tibia was used for determining bone mineral density (BMD) and bone ash coefficient. The HE and alizarin red S staining of femur were employed to evaluate bone pathology and calcium deposition. The expressions of alkaline phosphatase (ALP), insulin growth factor 1 (IGF-1) and cathepsin K were assessed by western blotting and immunohistochemical staining. KEY FINDINGS: JTXK granule significantly improved the bone ash coefficient, the distribution of trabecular bone and the calcification nodules deposition in KK-Ay mice with diabetes. IGF-1 and ALP expressions were significantly decreased, and cathepsin K expression was dramatically increased in the HFD fed KK-Ay diabetic model mice, which can be reversed by JTXK granule treatment. JTXK granule at medium or high dosage was more efficient in improving diabetic bone quality when compared with that in mice with a low dosage. However, the BMD values in each group of KK-Ay diabetic mice were not significantly different. SIGNIFICANCE: We demonstrate that cathepsin K expression is increased in KK-Ay diabetic mouse model. JTXK granule treatment inhibits osteoclastic bone resorption and promotes the new bone formation by decreasing cathepsin K activity and increasing IGF-1 and ALP levels. These changes may contribute to the increase of bone strength and thus reducing the risk of bone fractures. PMID- 26892149 TI - Aggression on inpatient units: Clinical characteristics and consequences. AB - Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation. PMID- 26892150 TI - Erratum. PMID- 26892151 TI - Management of Metastatic HER2-Positive Breast Cancer: Where Are We and Where Do We Go From Here? AB - Human epidermal growth factor receptor 2 (HER2)/neu-positive breast cancer has changed from being an aggressive disease with a poor prognosis to a disease that is highly treatable, with prolonged survival possible even in patients with metastatic disease. A better understanding of HER2 biology has led to the development of powerful targeted therapies, and four drugs are already approved by the US Food and Drug Administration for treatment in the metastatic setting (trastuzumab, pertuzumab, lapatinib, and trastuzumab emtansine). Optimizing how these drugs are delivered and in what sequence is an important part of modern management of HER2-positive breast cancer. However, while the prognosis has improved, metastatic disease is still not curable; newer, better drugs are needed. This review will summarize the current standard of care; key issues that arise when treating patients with HER2-positive disease; and developments in novel therapeutics, including small-molecule inhibitors, nanoparticles, immunotherapy, and agents targeting resistance pathways. PMID- 26892152 TI - Metastatic HER2-Positive Breast Cancer: Tailoring Treatment Un-'TIL' We Get It Right... PMID- 26892153 TI - Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer. AB - Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical markers are routinely employed in the diagnosis of epithelial ovarian carcinomas. However, molecular testing of these tumors, unlike in endometrial carcinoma, is not routinely used in clinical practice. PMID- 26892154 TI - Ovarian Carcinoma Histotypes: Their Emergence as Important Prognostic and Predictive Markers. PMID- 26892155 TI - Man With Recurring Chordoma and Progressive Disease Despite Radiotherapy and Radical Resection. PMID- 26892157 TI - Greater adverse effects of alcohol consumption in deprived communities are explained in study. PMID- 26892156 TI - Characters related to higher starch accumulation in cassava storage roots. AB - Cassava (Manihot esculenta) is valued mainly for high content starch in its roots. Our understanding of mechanisms promoting high starch accumulation in the roots is, however, still very limited. Two field-grown cassava cultivars, Huanan 124(H124) with low root starch and Fuxuan 01(F01) with high root starch, were characterised comparatively at four main growth stages. Changes in key sugars in the leaves, stems and roots seemed not to be strongly associated with the final amount of starch accumulated in the roots. However, when compared with H124, F01 exhibited a more compact arrangement of xylem vascular bundles in the leaf axils, much less callose around the phloem sieve plates in the stems, higher starch synthesis-related enzymatic activity but lower amylase activity in the roots, more significantly up-regulated expression of related genes, and a much higher stem flow rate (SFR). In conclusion, higher starch accumulation in the roots results from the concurrent effects of powerful stem transport capacity highlighted by higher SFR, high starch synthesis but low starch degradation in the roots, and high expression of sugar transporter genes in the stems. A model of high starch accumulation in cassava roots was therefore proposed and discussed. PMID- 26892158 TI - Efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer: a systematic review and meta-analysis. AB - AIM: Chronomodulated chemotherapy has been reported to be superior to conventional chemotherapy, but the results from randomized controlled trials (RCTs) are inconsistent. We performed a meta-analysis to summarize the efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer. METHODS: A literature search for relevant RCTs comparing the efficacy and safety of chronomodulated chemotherapy and conventional chemotherapy was performed. The main outcomes were overall survival (OS), objective response rate (ORR) and toxicity (grade 3/4), which included vomiting and nausea, diarrhea, mucositis, neutropenia and peripheral sensory neuropathy. Pooled relative risks (RRs) and hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were estimated. RESULTS: Six RCTs involving 1347 patients were included. Chronomodulated chemotherapy showed no advantages for OS (HR = 0.95; 95% CI, 0.84-1.08; P = 0.463) or ORR (RR = 1.06; 95% CI, 0.81-1.39; P = 0.499). The two groups were similar in terms of grade 3/4 vomiting and nausea (RR = 1.02; 95% CI, 0.78-1.35; P = 0.872), diarrhea (RR = 1.44; 95% CI, 0.87-2.36; P = 0.149) or peripheral sensory neuropathy (RR = 0.86; 95% CI, 0.56-1.34; P = 0.512), whereas decreased risks of mucositis (RR = 0.31; 95% CI, 0.14-0.66; P = 0.000) and neutropenia (RR = 0.40; 95% CI, 0.27-0.57; P = 0.000) were observed in chronomodulated chemotherapy. CONCLUSION: Chronomodulated chemotherapy may be favorable to reduce the risks of certain side effects, but there is no current evidence for improvement in OS or ORR. Our analysis suggests that the available data does not support the use of chronomodulated chemotherapy. PMID- 26892159 TI - Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. AB - Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. PMID- 26892161 TI - Acetaminophen attenuates error evaluation in cortex. AB - Acetaminophen has recently been recognized as having impacts that extend into the affective domain. In particular, double blind placebo controlled trials have revealed that acetaminophen reduces the magnitude of reactivity to social rejection, frustration, dissonance and to both negatively and positively valenced attitude objects. Given this diversity of consequences, it has been proposed that the psychological effects of acetaminophen may reflect a widespread blunting of evaluative processing. We tested this hypothesis using event-related potentials (ERPs). Sixty-two participants received acetaminophen or a placebo in a double blind protocol and completed the Go/NoGo task. Participants' ERPs were observed following errors on the Go/NoGo task, in particular the error-related negativity (ERN; measured at FCz) and error-related positivity (Pe; measured at Pz and CPz). Results show that acetaminophen inhibits the Pe, but not the ERN, and the magnitude of an individual's Pe correlates positively with omission errors, partially mediating the effects of acetaminophen on the error rate. These results suggest that recently documented affective blunting caused by acetaminophen may best be described as an inhibition of evaluative processing. They also contribute to the growing work suggesting that the Pe is more strongly associated with conscious awareness of errors relative to the ERN. PMID- 26892164 TI - 5th Conference of the EHSF 2016, February 10-12, 2016, Langenbeck-Virchow Haus, Berlin, Germany. PMID- 26892162 TI - Adding insult to injury: neural sensitivity to social exclusion is associated with internalizing symptoms in chronically peer-victimized girls. AB - Despite evidence documenting activation of the social pain network in response to social rejection and its link to temporary distress, far less is known regarding its role in pervasive emotional difficulties. Moreover, research has not considered the intersection between neural activation to experimentally induced social exclusion and naturally occurring social adversity. This study examined an integrated social pain model of internalizing symptoms, which posits that (i) neural sensitivity in the social pain network is associated with internalizing symptoms, (ii) this linkage is more robust in youth with than without a history of social adversity, and (iii) heightened avoidance motivation serves as one pathway linking neural sensitivity and internalizing symptoms. During a functional magnetic resonance imaging scan, 47 adolescent girls (M age = 15.46 years, SD = .35) with well-characterized histories of peer victimization were exposed to social exclusion. Whole-brain analyses revealed that activation to exclusion in the social pain network was associated with internalizing symptoms. As anticipated, this linkage was stronger in chronically victimized than non victimized girls and was partially accounted for by avoidance motivation. This research indicates the importance of integrating neural, social and psychological systems of development in efforts to elucidate risk for internalizing symptoms among adolescent girls. PMID- 26892163 TI - Spirocyclopropanation Reaction of para-Quinone Methides with Sulfonium Salts: The Synthesis of Spirocyclopropanyl para-Dienones. AB - A novel DBU-mediated stereoselective spirocyclopropanation of para-quinone methides with sulfonium salts has been developed on the basis of the mode involving a 1,6-conjugate addition/intramolecular dearomatizing cyclization cascade. This reaction provides a mild and effective method for the assembly of synthetically and structurally interesting spirocyclopropanyl para-dienones. The feasibility for the enantioselective access to such functionalized para-dienones has also been explored by using the axially chiral sulfonium salt. Importantly, the regioselective ring openings of the related spirocyclopropanyl para-dienones have been achieved divergently. PMID- 26892160 TI - Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project. AB - PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice. PMID- 26892165 TI - Application of brain multi-b-value diffusion-weighted imaging (DWI) in adolescent orphans from AIDS families. AB - OBJECTIVE: To evaluate the application value of multi-b-value diffusion-weighted imaging (DWI) with mono-exponential model and stretched-exponential model in the diagnosis of HIV-positive patients. METHODS: Multi-b-value (0, 50, 150, 200, 400, 600, 800 s mm(-2)) DWI was performed in 23 adolescent orphans from AIDS families, including 15 HIV-positive subjects and 8 HIV-negative healthy subjects. Apparent diffusion coefficient (ADC) values were fitted by mono-exponential model; distribution diffusion coefficient (DDC) values and heterogeneity index (alpha) values were fitted by stretched-exponential model in bilateral basal ganglia, then non-parametric tests were performed. RESULTS: The signal intensity attenuation in multi-b-value DWI could be well described by both mono-exponential model and stretched-exponential model. In the left basal ganglia, mean alpha values in HIV-positive subjects (alpha = 0.848 +/- 0.068) were significantly lower than that in healthy subjects (alpha = 0.923 +/- 0.050, p = 0.013). There was no statistical difference of alpha-values between HIV-positive subjects and healthy control subjects in the right basal ganglia. Apart from these, there were also no statistical differences of DDC values or ADC values between two groups in bilateral basal ganglia (all p > 0.05). In bilateral basal ganglia, DDC values were positively correlated with ADC values in HIV-positive patients (right basal ganglia: r = 0.832, p = 0.000; left basal ganglia: r = 0.770, p = 0.001) as well as in healthy cases (right basal ganglia: r = 0.927, p = 0.001; left basal ganglia: r = 0.878, p = 0.004). Receiver operating characteristic (ROC) curve analysis yielded area under the ROC curve (Az) values of 0.817 (p = 0.014 < 0.05) in the left basal ganglia. The sensitivity and specificity were 62.5% and 86.7%, respectively. CONCLUSION: Through the study of asymptomatic HIV-positive subjects when b < 1000 s mm(-2), we can see stretched-exponential model DWI can provide more information than mono-exponential model DWI. ADVANCES IN KNOWLEDGE: Multi-b value DWI was performed in subjects with HIV. DWI measurements could be neuroimaging biomarkers of cerebral injury in the course of HIV infection. PMID- 26892166 TI - Ectopic Pancreas in the Wall of the Small Intestine. AB - Ectopic pancreas is an uncommon and benign finding. However, these lesions can cause symptoms including abdominal pain and often require removal. We present the case of a 27-year-old patient with long-standing vague abdominal symptoms eventually found to have ectopic pancreas tissue in the proximal jejunum. PMID- 26892167 TI - Pancreatic Metastasectomy-an Analysis of Survival Outcomes and Prognostic Factors. AB - BACKGROUND: The pancreas and peripancreatic region may be a site of metastasis from distant sites. Recent data suggest that pancreatic metastasectomy may achieve long-term survival. We seek to examine our experience with this metastasectomy by reporting the perioperative and survival outcomes. METHODS: Patients undergoing resection of isolated pancreatic metastasis were identified from a prospective pancreatic surgical database at the Department of Gastrointestinal Surgery, North Shore campus of the University of Sydney between January 2004 and June 2015 and selected for retrospective review. Data on operative morbidity and mortality were reported. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Fifteen patients underwent pancreatic metastasectomy after a median disease-free interval of 63 months (range 0 to 199). Pancreatoduodenectomy was performed in six patients (40 %), distal pancreatectomy with or without splenectomy in three patients (20 %), and pancreatectomy with other visceral organ resection in six patients (40 %). Major complications occurred in six patients (40 %) without mortality. The median survival was 40 months (95 % CI 24.3 to 53.7), and 1-, 3-, and 5-year survival were 76, 48, and 31 % respectively. Cox proportional hazard model identified margin negative resection (hazard ratio (HR) 10.5; P = 0.044) as a predictor of improved survival. CONCLUSION: Long-term survival may be achieved in selected patients with pancreatic metastasis through pancreatic metastasectomy with acceptable morbidity. Selection of patients should be individualized and based on their primary disease origin, biological behavior of the tumor, resectability of the tumor, and the relative effectiveness of systemic or targeted therapies. PMID- 26892168 TI - High Incidence of Redo Surgery After Frey Procedure for Chronic Pancreatitis in the Long-Term Follow-up. PMID- 26892169 TI - The Influence of Structure Heights and Opening Angles of Micro- and Nanocones on the Macroscopic Surface Wetting Properties. AB - We discuss the influence of surface structure, namely the height and opening angles of nano- and microcones on the surface wettability. We show experimental evidence that the opening angle of the cones is the critical parameter on sample superhydrophobicity, namely static contact angles and roll-off angles. The textured surfaces are fabricated on silicon wafers by using a simple one-step method of reactive ion etching at different processing time and gas flow rates. By using hydrophobic coating or hydrophilic surface treatment, we are able to switch the surface wettability from superhydrophilic to superhydrophobic without altering surface structures. In addition, we show examples of polymer replicas (polypropylene and poly(methyl methacrylate) with different wettability, fabricated by injection moulding using templates of the silicon cone-structures. PMID- 26892172 TI - Delayed seizure control with responsive neurostimulation: patience is a virtue. PMID- 26892170 TI - SNP discovery and genetic mapping using genotyping by sequencing of whole genome genomic DNA from a pea RIL population. AB - BACKGROUND: Progress in genetics and breeding in pea still suffers from the limited availability of molecular resources. SNP markers that can be identified through affordable sequencing processes, without the need for prior genome reduction or a reference genome to assemble sequencing data would allow the discovery and genetic mapping of thousands of molecular markers. Such an approach could significantly speed up genetic studies and marker assisted breeding for non model species. RESULTS: A total of 419,024 SNPs were discovered using HiSeq whole genome sequencing of four pea lines, followed by direct identification of SNP markers without assembly using the discoSnp tool. Subsequent filtering led to the identification of 131,850 highly designable SNPs, polymorphic between at least two of the four pea lines. A subset of 64,754 SNPs was called and genotyped by short read sequencing on a subpopulation of 48 RILs from the cross 'Baccara' x 'PI180693'. This data was used to construct a WGGBS-derived pea genetic map comprising 64,263 markers. This map is collinear with previous pea consensus maps and therefore with the Medicago truncatula genome. Sequencing of four additional pea lines showed that 33 % to 64 % of the mapped SNPs, depending on the pairs of lines considered, are polymorphic and can therefore be useful in other crosses. The subsequent genotyping of a subset of 1000 SNPs, chosen for their mapping positions using a KASPTM assay, showed that almost all generated SNPs are highly designable and that most (95 %) deliver highly qualitative genotyping results. Using rather low sequencing coverages in SNP discovery and in SNP inferring did not hinder the identification of hundreds of thousands of high quality SNPs. CONCLUSIONS: The development and optimization of appropriate tools in SNP discovery and genetic mapping have allowed us to make available a massive new genomic resource in pea. It will be useful for both fine mapping within chosen QTL confidence intervals and marker assisted breeding for important traits in pea improvement. PMID- 26892171 TI - Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device. AB - In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole. PMID- 26892173 TI - Figure analysis: An implementation dialogue. AB - Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver information to students. Here, a "how to" guide is presented in the form of an in-class dialogue, displaying the difficulties in visual interpretation that some students may experience while figure analysis is being implemented in an upper-level, cell biology course. Additionally, the dialogue serves as a guide for instructors who may implement the active learning technique as they consider how to respond to students' concerns in class. (c) 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):345-348, 2016. PMID- 26892174 TI - Estimating optimal treatment regimes via subgroup identification in randomized control trials and observational studies. AB - With new treatments and novel technology available, personalized medicine has become an important piece in the new era of medical product development. Traditional statistics methods for personalized medicine and subgroup identification primarily focus on single treatment or two arm randomized control trials. Motivated by the recent development of outcome weighted learning framework, we propose an alternative algorithm to search treatment assignments which has a connection with subgroup identification problems. Our method focuses on applications from clinical trials to generate easy to interpret results. This framework is able to handle two or more than two treatments from both randomized control trials and observational studies. We implement our algorithm in C++ and connect it with R. Its performance is evaluated by simulations, and we apply our method to a dataset from a diabetes study. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892175 TI - Epitope mapping of Brugia malayi ALT-2 and the development of a multi-epitope vaccine for lymphatic filariasis. AB - Human lymphatic filariasis is a neglected tropical disease, causing permanent and long-term disability with severe immunopathology. Abundant larval transcript (ALT) plays a crucial role in parasite establishment in the host, due to its multi-faceted ability in host immune regulation. Although ALT protein is a key filarial target, its exact function is yet to be explored. Here, we report epitope mapping and a structural model of Brugia malayi ALT-2, leading to development of a multi-epitope vaccine. Structural analysis revealed that ALT represents unique parasitic defence proteins belonging to a toxin family that carries a 'knottin' fold. ALT-2 has been a favourite vaccine antigen and was protective in filarial models. Due to the immunological significance of ALT-2, we mapped B-cell epitopes systematically and identified two epitope clusters, 1-30 and 89-128. To explore the prophylactic potential of epitope clusters, a recombinant multi-epitopic gene comprising the epitopic domains was engineered and the protective efficacy of recombinant ALT epitope protein (AEP) was tested in the permissive model, Mastomys coucha. AEP elicited potent antibody responses with predominant IgG1 isotype and conferred significantly high protection (74.59%) compared to ALT-2 (61.95%). This proved that these epitopic domains are responsible for the protective efficacy of ALT-2 and engineering protective epitopes as a multi-epitope protein may be a novel vaccine strategy for complex parasitic infections. PMID- 26892176 TI - Focal Mechanical Vibration Does not Change Laser-Pain Perception and Laser-Evoked Potentials: A Pilot Study. AB - BACKGROUND: Nonpainful tactile and electrical stimulation of the large myelinated fibers reduces spontaneous pain and the amplitude of laser-evoked potentials (LEPs), which represent the most reliable technique to assess the nociceptive pathway function. Focal mechanical vibration stimulates the Abeta afferents selectively; thus, it is conceivable its action on nociceptive pathways. AIM: The aim of this study was to investigate the effect of vibratory stimuli, activating either both muscle and skin receptors or cutaneous afferents only on the LEPs and subjective laser-pain rating. METHODS: Ten healthy volunteers were studied. The subjects were evaluated in two different sessions to test muscle and skin receptors or cutaneous afferents only. In each session, LEPs were recorded to stimulation of the dorsal hand skin in radial and ulnar territory bilaterally, while the vibratory stimulus was delivered on the radial territory of the right forearm. RESULTS: The results showed a substantial stability of the potential N1 and N2/P2 after the two protocols, with a declining trend from the initial to the last test of the same session, probably due to habituation. Accordingly, the laser-pain perception did not change during the experimental setting. CONCLUSIONS: We conclude that a vibratory stimulus is ineffective in reducing the laser-evoked potentials and laser-pain perception. PMID- 26892177 TI - Downregulation of cytokeratin 18 is associated with paclitaxel-resistance and tumor aggressiveness in prostate cancer. AB - Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients. PMID- 26892178 TI - Usefulness of opening pressure grading just prior to Ahmed glaucoma valve implantation to predict early postoperative hypotony. PMID- 26892179 TI - Stereoselective synthesis and structural elucidation of dicarba peptides. AB - A facile stereoselective synthesis of cis and trans unsaturated dicarba peptides has been established using preformed diaminosuberic acid derivatives as bridging units. In addition, characteristic spectral differences in the (13)C-NMR spectra of the cis- and trans-isomers show that the chemical shift of carbons in the Delta4,5-diaminosuberic acid residue can be used to assign stereochemistry in unsaturated dicarba peptides formed from ring closing metathesis of linear peptide sequences. PMID- 26892180 TI - Early detection of germinated wheat grains using terahertz image and chemometrics. AB - In this paper, we propose a feasible tool that uses a terahertz (THz) imaging system for identifying wheat grains at different stages of germination. The THz spectra of the main changed components of wheat grains, maltose and starch, which were obtained by THz time spectroscopy, were distinctly different. Used for original data compression and feature extraction, principal component analysis (PCA) revealed the changes that occurred in the inner chemical structure during germination. Two thresholds, one indicating the start of the release of alpha amylase and the second when it reaches the steady state, were obtained through the first five score images. Thus, the first five PCs were input for the partial least-squares regression (PLSR), least-squares support vector machine (LS-SVM), and back-propagation neural network (BPNN) models, which were used to classify seven different germination times between 0 and 48 h, with a prediction accuracy of 92.85%, 93.57%, and 90.71%, respectively. The experimental results indicated that the combination of THz imaging technology and chemometrics could be a new effective way to discriminate wheat grains at the early germination stage of approximately 6 h. PMID- 26892181 TI - Aeromicrobium halotolerans sp. nov., isolated from desert soil sample. AB - A Gram-positive, aerobic, and non-motile, rod-shaped actinomycete strain, designated YIM Y47(T), was isolated from soils collected from Turpan desert, China, and subjected to a polyphasic taxonomic study. Phylogenetic analysis indicated that strain YIM Y47(T) belonged to the genus Aeromicrobium. YIM Y47(T) shared highest 16S rRNA gene sequence similarities with Aeromicrobium massiliense JC14(T) (96.47 %). Growth occurs at 20-45 degrees C (optimum at 30 degrees C), pH 6.0-8.0 (optimum at pH 7.0), and salinities of 0-7.0 % NaCl (optimum at 4.0 %). The strain YIM Y47(T) exhibits chemotaxonomic features with menaquinone-7 (MK 7) as the predominant quinone, C16:0, C18:1 omega9c and 10-methyl C18:0 (>10 %) as major fatty acids. The cell-wall peptidoglycan of strain YIM Y47(T) contained LL-diaminopimelic acid as the diagnostic diamino acid. The polar lipids were found to consist of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, and unknown phospholipids. The G+C content of the genomic DNA of strain YIM Y47(T) was found to be 44.7 mol%. On the basis of phylogenetic analyses and phenotypic data, it is proposed that strain YIM Y47(T) should be classified as representing a novel species of the genus Aeromicrobium, with the name Aeromicrobium halotolerans sp. nov. The type strain is YIM Y47(T) (=KCTC 39113(T)=CGMCC 1.15063(T)=DSM 29939(T)=JCM 30627(T)). PMID- 26892183 TI - Molecular cloning of plane pollen allergen Pla a 3 and its utility as diagnostic marker for peach associated plane pollen allergy. AB - BACKGROUND: Non-specific lipid transfer proteins (nsLTP) are considered to provoke allergic symptoms to plane tree pollen, which are frequently associated with peach allergy. OBJECTIVE: The objective was to clone the cDNA of plane pollen nsLTP Pla a 3, to characterize IgE-binding and allergenic potency of recombinant Pla a 3 in comparison to its natural counterpart and peach nsLTP Pru p 3. METHODS: Natural Pla a 3 was purified from plane pollen and analysed by mass spectrometry (MS). Recombinant Pla a 3 was characterized by SDS-PAGE and CD spectroscopy. Specific IgE to extract, components of plane pollen and Pru p 3 was measured by ImmunoCAP in sera of patients allergic to either plane pollen (n = 10), peach (n = 15) or both (n = 15). Biological potency of the proteins was investigated by in vitro mediator release assays and IgE cross-reactivity by competitive ELISA. RESULTS: Two Pla a 3 isoforms were identified. Recombinant Pla a 3 showed high purity, structural integrity, IgE-binding capacity comparable to nPla a 3 and biological potency. Sensitization to plane pollen extract was confirmed in 24/25 plane pollen allergics. The frequency of sensitization to Pla a 3 was 53% among patients allergic to both plane pollen and peach and 10% among plane pollen allergics tolerating peach where most patients were sensitized to Pla a 1. Pla a 3 and Pru p 3 showed strong bi-directional IgE cross-reactivity in patients allergic to peach and plane pollen, but not in peach allergics tolerating plane pollen. Levels of IgE-binding were generally higher to Pru p 3 than to Pla a 3. CONCLUSION: Sensitization to Pla a 3 is relevant in a subgroup of plane pollen allergics with concomitant peach allergy. IgE testing with Pla a 3 may serve as a marker to identify plane pollen allergic patients at risk of LTP mediated food reactions and thereby improve in vitro diagnostic procedures. PMID- 26892185 TI - Dominance relationships in male Nepal gray langurs (Semnopithecus schistaceus). AB - OBJECTIVES: Reproductive skew is proposed to link to despotism in dominance hierarchies. While studies illustrating male skew are plentiful, demonstrating the link to despotism is rare. Likewise, it is often unknown which factors (e.g., resource holding potential, age, physical condition) affect a male's dominance rank. Here we investigated correlates of male rank and hierarchy characteristics in Nepal gray langurs (Semnopithecus schistaceus), a population with high male reproductive skew, and compared the results to other multi-male groups of nonhuman primates. METHODS: We collected dyadic displacement interactions from two groups (mean 3.0 and 4.1 adult males) for five years each. We assessed dominance ranks for demographically stable phases (n = 11, n = 28) and analyzed the effects of age and physical condition through linear mixed models (LMM). We analyzed hierarchy characteristics via the program MatMan. We used data from 27 primate groups (cercopithecines, colobines, hominoids) as a comparative sample. RESULTS: The highest ranks were attained by adults in one group (LMM, P < 0.091) and by young adults in the other group (LMM, P < 0.001). With some exceptions, rank was highest for males with higher physical condition scores (LMM, P < 0.05). Hierarchies had high directional consistency (mean > 0.93) and linearity (mean >0.81) and were relatively steep (mean >0.66) when compared with other species. DISCUSSION: Dominance rank followed a pattern predicted by resource holding potential, but other individual attributes and group composition also seemed important. As predicted, hierarchy characteristics indicated a despotic system in line with the strong reproductive skew. Across primates, however, the degree of despotism did not appear to match the degree of reproductive skew. Am J Phys Anthropol 160:208-219, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26892182 TI - Synthesis and Biological Evaluation of Pentacycloundecylamines and Triquinylamines as Voltage-Gated Calcium Channel Blockers. AB - Preclinical studies for neurodegenerative diseases have shown a multi-targeted approach to be successful in the treatment of these complex disorders with several pathoetiological pathways. Polycyclic compounds, such as NGP1-01 (7a), have demonstrated the ability to target multiple mechanisms of the complex etiology and are referred to as multifunctional compounds. These compounds have served as scaffolds with the ability to attenuate Ca(2+) overload and excitotoxicity through several pathways. In this study, our focus was on mitigating Ca(2+) overload through the L-type calcium channels (LTCC). Here, we report the synthesis and biological evaluation of several novel polycyclic compounds. We determined the IC50 values for both the pentacycloundecylamines and the triquinylamines by means of a high-throughput fluorescence calcium flux assay utilizing Fura-2/AM. The potential of these compounds to offer protection against hydrogen peroxide-induced cell death was also evaluated. Overall, 8-benzylamino 8,11-oxapentacyclo[5.4.0.0(2,6) .0(3,10) .0(5,9) ]undecane (NGP1-01, 7a) had the most favorable pharmacological profile with an IC50 value of 86 uM for LTCC inhibition and significant reduction of hydrogen peroxide-induced cell death. In general, the triquinylamines were more active as LTCC blockers than the oxa pentacycloundecylamines. The aza-pentacycloundecylamines were potent LTCC inhibitors, with 8-hydroxy-N-phenylethyl-8,11-azapentacyclo[5.4.0.0(2,6) .0(3,10) .0(5,9) ]undecane (8b) also able to offer significant protection in the cell viability assays. PMID- 26892184 TI - Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications. AB - Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naive patients with schizophrenia, as well as in the animal models of both drug-naive rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKalpha (NPY: neuropeptide Y; AMPKalpha: AMP-activated protein kinase alpha) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKalpha-SREBP-1-PPARalpha-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARalpha: Peroxisome proliferator activated receptor-alpha) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental disorders. PMID- 26892187 TI - New Facial Weakness After 5 Years of Facial Asymmetry. PMID- 26892186 TI - Volatile Oil of Acori Graminei Rhizoma-Induced Apoptosis and Autophagy are dependent on p53 Status in Human Glioma Cells. AB - Acori Graminei Rhizoma is well known for the beneficial effects on CNS disorders in traditional medicine. Though it is frequently prescribed in formulations for brain tumors, the anti-glioma effect has not been examined. We used volatile oil of Acori Graminei Rhizoma (VOA) and human glioblastoma multiforme (GBM) cells in this study. We found that VOA exhibited greater growth suppression in p53 wild type cells than p53 mutant cells and very low effect on fibroblasts and human glial HEB cells. Apoptosis was triggered by VOA with a caspase-dependent way in p53 wild-type A172 cells, while a caspase-independent way in p53 mutant U251 cells. Meanwhile, both A172 and U251 cells treated by VOA displayed autophagic features. Furthermore, p53 decrease was observed along with VOA-induced apoptosis and autophagy in A172 cells. VOA-induced autophagy was mediated through a p53/AMPK/mTOR signaling pathway in A172 cells, while an mTOR-independent signaling pathway in U251 cells. Finally, blockage of autophagy potentiated the proapoptotic effect in both A172 and U251 cells, indicating a protective role of autophagy in VOA-induced cell death. Together, VOA exhibited anti-tumor activity in human GBM cells and induced apoptotic cell death and protective autophagy, which is cell type specific and dependent on p53 status. PMID- 26892189 TI - Musculoskeletal architecture of the prey capture apparatus in salamandrid newts with multiphasic lifestyle: does anatomy change during the seasonal habitat switches? AB - Some newt species change seasonally between an aquatic and a terrestrial life as adults, and are therefore repeatedly faced with different physical circumstances that affect a wide range of functions of the organism. For example, it has been observed that seasonally habitat-changing newts display notable changes in skin texture and tail fin anatomy, allowing one to distinguish an aquatic and a terrestrial morphotype. One of the main functional challenges is the switch between efficient aquatic and terrestrial prey capture modes. Recent studies have shown that newts adapt quickly by showing a high degree of behavioral flexibility, using suction feeding in their aquatic stage and tongue prehension in their terrestrial stage. As suction feeding and tongue prehension place different functional demands on the prey capture apparatus, this behavioral flexibility may clearly benefit from an associated morphological plasticity. In this study, we provide a detailed morphological analysis of the musculoskeletal system of the prey capture apparatus in the two multiphasic newt species Ichthyosaura alpestris and Lissotriton vulgaris by using histological sections and micro-computed tomography. We then test for quantitative changes of the hyobranchial musculoskeletal system between aquatic and terrestrial morphotypes, The descriptive morphology of the cranio-cervical musculoskeletal system provides new insights on form and function of the prey capture apparatus in newts, and the quantitative approach shows hypertrophy of the hyolingual musculoskeletal system in the terrestrial morphotype of L. vulgaris but hypertrophy in the aquatic morphotype of I. alpestris. It was therefore concluded that the seasonal habitat shifts are accompanied by a species-dependent muscular plasticity of which the potential effect on multiphasic feeding performance in newts remains unclear. PMID- 26892188 TI - Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains. AB - Intracerebral complement activation after severe traumatic brain injury (TBI) leads to a cascade of neuroinflammatory pathological sequelae that propagate host mediated secondary brain injury and adverse outcomes. There are currently no specific pharmacological agents on the market to prevent or mitigate the development of secondary cerebral insults after TBI. A novel chimeric CR2-fH compound (mTT30) provides targeted inhibition of the alternative complement pathway at the site of tissue injury. This experimental study was designed to test the neuroprotective effects of mTT30 in a mouse model of closed head injury. The administration of 500 MUg mTT30 i.v. at 1 h, 4 h and 24 h after head injury attenuated complement C3 deposition in injured brains, reduced the extent of neuronal cell death, and decreased post-injury microglial activation, compared to vehicle-injected placebo controls. These data imply that site-targeted alternative pathway complement inhibition may represent a new promising therapeutic avenue for the future management of severe TBI. PMID- 26892190 TI - Dramatic pressure-driven enhancement of bulk skyrmion stability. AB - The recent discovery of magnetic skyrmion lattices initiated a surge of interest in the scientific community. Several novel phenomena have been shown to emerge from the interaction of conducting electrons with the skyrmion lattice, such as a topological Hall-effect and a spin-transfer torque at ultra-low current densities. In the insulating compound Cu2OSeO3, magneto-electric coupling enables control of the skyrmion lattice via electric fields, promising a dissipation-less route towards novel spintronic devices. One of the outstanding fundamental issues is related to the thermodynamic stability of the skyrmion lattice. To date, the skyrmion lattice in bulk materials has been found only in a narrow temperature region just below the order-disorder transition. If this narrow stability is unavoidable, it would severely limit applications. Here we present the discovery that applying just moderate pressure on Cu2OSeO3 substantially increases the absolute size of the skyrmion pocket. This insight demonstrates directly that tuning the electronic structure can lead to a significant enhancement of the skyrmion lattice stability. We interpret the discovery by extending the previously employed Ginzburg-Landau approach and conclude that change in the anisotropy is the main driver for control of the size of the skyrmion pocket. PMID- 26892191 TI - Audit feedback on reading performance of screening mammograms: An international comparison. AB - OBJECTIVE: Providing feedback to mammography radiologists and facilities may improve interpretive performance. We conducted a web-based survey to investigate how and why such feedback is undertaken and used in mammographic screening programmes. METHODS: The survey was sent to representatives in 30 International Cancer Screening Network member countries where mammographic screening is offered. RESULTS: Seventeen programmes in 14 countries responded to the survey. Audit feedback was aimed at readers in 14 programmes, and facilities in 12 programmes. Monitoring quality assurance was the most common purpose of audit feedback. Screening volume, recall rate, and rate of screen-detected cancers were typically reported performance measures. Audit reports were commonly provided annually, but more frequently when target guidelines were not reached. CONCLUSION: The purpose, target audience, performance measures included, form and frequency of the audit feedback varied amongst mammographic screening programmes. These variations may provide a basis for those developing and improving such programmes. PMID- 26892192 TI - Surgical treatment of posterior nutcracker syndrome presented with hyperaldosteronism. AB - Posterior nutcracker syndrome is caused by the compression of left renal vein between the abdominal aorta and the vertebral body. Most seen symptoms are haematuria, left flank pain, abdominal pain and varicocele. The nutcracker syndrome may lead to left renal vein thrombosis due to blood congestion within compression of the vessel. Both endovascular and open surgical interventions can relieve symptoms; however, traditional surgical repair is still considered as the gold standard. Here, we present the surgical treatment of a 36-year old female with complaints of hypertension, hyperaldosteronism and diagnosed with posterior nutcracker syndrome. PMID- 26892193 TI - Prospective validation of a predictive scoring system for deep sternal wound infection after routine bilateral internal thoracic artery grafting. AB - OBJECTIVES: The Gatti score is a weighted scoring system based on risk factors for deep sternal wound infection (DSWI) that has been specifically created to predict DSWI risk after routine bilateral internal thoracic artery (BITA) grafting. It has not undergone an external validation. The aim of the present study was to perform this validation. METHODS: BITA grafts were used as skeletonized conduits in 304 (90.7%) of 335 consecutive patients with multivessel coronary artery disease who underwent isolated coronary bypass surgery at the authors' institution between January 2014 and July 2015. Baseline characteristics, operative data and immediate outcomes of every patient were prospectively collected in a computerized data registry. A score was assigned to each patient preoperatively. The goodness-of-fit and the discrimination power of both models, preoperative and combined, of the Gatti score were assessed with the Hosmer-Lemeshow test and the calculation of the area under the receiver-operating characteristic curve, respectively. RESULTS: Eighteen (5.9%) patients suffered from DSWI. Major differences were found between the original series whence the Gatti score has been derived and the present prospective series. The Gatti score goodness-of-fit was satisfactory for both the preoperative (P = 0.61) and the combined model (P = 0.81). The area under the receiver-operating characteristic curve was 0.82 (95% confidence interval: 0.72-0.91) for the preoperative model and 0.8 (95% confidence interval: 0.71-0.9) for the combined model. CONCLUSIONS: On the basis of the results of the present prospective study, the Gatti score has proved to be effective in predicting DSWI following BITA grafting despite some differences between the original and the present series of patients. More studies have to be performed in order to strengthen the evidence of this first external validation. PMID- 26892194 TI - Multicentre, propensity-matched study to evaluate long-term impact of implantation technique in isolated aortic valve replacement on mortality and incidence of redo surgery. AB - OBJECTIVES: Studies suggest that the use of semicontinuous suture (SC) technique increases the risk of redo valve surgery after aortic valve replacement (AVR). The objective of this study was to identify 30-day mortality, rate of redo operation and long-term outcomes after AVR using either a semicontinuous suture or interrupted suture (IS) technique. METHODS: A total of 1617 patients from 2 cardiothoracic centres, undergoing isolated AVR between April 2005 and August 2013 were included. AVR was performed using SC technique in 765 patients and IS technique in 852 patients. Data were collected prospectively and follow-up was obtained to date for all patients. We compared 30-day mortality, rate of redo operation and long-term mortality in SC and IS groups. One-to-one propensity matching analysis was performed using IBM SPSS version 22 to evaluate outcomes. RESULTS: Four hundred and eleven patients in the SC group were matched to 411 patients in the IS group (total of 822 patients) using propensity-score matching. The baseline characteristics were similar between SC and IS groups after matching. There were no statistically significant differences in 30-day mortality (3.9 vs 2.7%; P = 0.328), long-term mortality at 9-year follow-up (14.4 vs 15.3%; log-rank = 0.524) or rate of redo surgery (2.9 vs 2.0%; P = 0.320) between SC and IS, respectively. However, shorter cross-clamp time (51.9 +/- 15.2 vs 60.9 +/- 17.6 min; P < 0.001), bypass time (71.3 +/- 23.0 vs 81.3 +/- 37.8 min; P < 0.001) and the use of larger valve sizes (23.4 +/- 2.1 vs 21.9 +/- 2.2 mm; P < 0.001) were observed in SC patients compared with IS patients. Multivariate analysis did not show the suture technique as a significant determinant of redo valve surgery. CONCLUSIONS: This multicentre study demonstrates that neither mortality nor the risk of redo surgery was influenced by the choice of implantation technique using semicontinuous vs interrupted suture techniques. The SC technique allowed shorter operations and larger size valves to be utilized. PMID- 26892195 TI - Aortic and/or mitral valve surgery in patients with pulmonary hypertension performed via a minimally invasive approach. AB - Pulmonary hypertension (PH) in the setting of left-sided valvular heart disease is common, and significantly increases the risk of perioperative morbidity and mortality in patients undergoing aortic and/or mitral valve surgery. Minimally invasive valve surgery is associated with a decreased incidence of perioperative complications, and a faster recovery, when compared with conventional sternotomy. In the present study, the outcomes of 569 patients with PH who underwent minimally invasive aortic and/or mitral valve surgery were analysed. The operative mortality was 3.5%, and postoperative strokes occurred in 1.4%. The mean intensive care unit and hospital length of stays were 50 +/- 14 h and 7 +/- 1 days, respectively. Patients with severe PH (mean pulmonary artery pressure >=40 mmHg) had a longer duration of postoperative ventilation and intensive care unit length of stay, when compared with mild/moderate PH, and similar clinical outcomes. In conclusion, a minimally invasive approach to aortic and/or mitral valve surgery in patients with PH is safe and feasible, and may be considered as an alternative to conventional median sternotomy. PMID- 26892196 TI - Disordered Eating, Compulsive Exercise, and Sport Participation in a UK Adolescent Sample. AB - The sport literature has produced equivocal results as to whether sport participation is a protective or risk factor for disordered eating. One mechanism by which it could be a risk factor is the increased drive or compulsion to exercise. This study compared the levels of disordered eating and compulsive exercise between adolescent sport and non-sport participants. A sample of 417 male and female adolescents, aged 14-16 years old, was recruited from UK secondary schools. Participants completed questionnaire packs that included: the Eating Disorder Inventory; a measure of exercise behaviour; and the Compulsive Exercise Test (CET). Non-sport participants reported significantly greater body dissatisfaction than sport participants, and this was true for boys and girls. Significant group differences were also reported for many of the CET scales, with sport participants generally reporting greater levels of compulsive exercise than non-sport participants. Implications of these results are discussed. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 26892197 TI - Fusarium mycotoxins in cereals harvested from Hungarian fields. AB - The Fusarium mycotoxins deoxynivalenol (DON), zearalenone (ZEN) and T-2 frequently contaminate grain crops in Middle and Eastern Europe. In this survey, 116 cereal samples (maize, wheat, barley and oat) were examined for DON, ZEN and T-2 mycotoxins. Samples were collected from different areas in two Hungarian regions (North and South Transdanubia). The method of analysis was indirect competitive ELISA. Maize was the most contaminated grain regarding DON (86%), ZEN (41%) and T-2 (55%) toxins. The average results of the deoxynivalenol and zearalenone tests of maize proved to be significantly higher than those of barley or oat. DON was the most represented Fusarium mycotoxin followed by T-2 and ZEN. The examination of these mycotoxins would be necessary at a larger scale as to re evaluate permissible levels, so increase of the monitoring programme would be advisable for the future. PMID- 26892198 TI - Loss of Control as a Discriminating Factor Between Different Latent Classes of Disordered Gambling Severity. AB - Analyses of disordered gambling assessment data have indicated that commonly used screens appear to measure latent categories. This stands in contrast to the oft held assumption that problem gambling is at the extreme of a continuum. To explore this further, we report a series of latent class analyses of a number of prevalent problem gambling assessments (PGSI, SOGS, DSM-IV Pathological Gambling based assessments) in nationally representative British surveys between 1999 and 2012, analysing data from nearly fifty thousand individuals. The analyses converged on a three class model in which the classes differed by problem gambling severity. This identified an initial class of gamblers showing minimal problems, a additional class predominantly endorsing indicators of preoccupation and loss chasing, and a third endorsing a range of disordered gambling criteria. However, there was considerable evidence to suggest that classes of intermediate and high severity disordered gamblers differed systematically in their responses to items related to loss of control, and not simply on the most 'difficult' items. It appeared that these differences were similar between assessments. An important exception to this was one set of DSM-IV criteria based analyses using a specific cutoff, which was also used in an analysis that identified an increase in UK problem gambling prevalence between 2007 and 2010. The results suggest that disordered gambling has a mixed latent structure, and that present assessments of problem gambling appear to converge on a broadly similar construct. PMID- 26892199 TI - Colonoscopy Surveillance After Colorectal Cancer Resection: Recommendations of the US Multi-Society Task Force on Colorectal Cancer. AB - The US Multi-Society Task Force has developed updated recommendations to guide health care providers with the surveillance of patients after colorectal cancer (CRC) resection with curative intent. This document is based on a critical review of the literature regarding the role of colonoscopy, flexible sigmoidoscopy, endoscopic ultrasound, fecal testing and CT colonography in this setting. The document addresses the effect of surveillance, with focus on colonoscopy, on patient survival after CRC resection, the appropriate use and timing of colonoscopy for perioperative clearing and for postoperative prevention of metachronous CRC, specific considerations for the detection of local recurrence in the case of rectal cancer, as well as the place of CT colonography and fecal tests in post-CRC surveillance. PMID- 26892200 TI - The role of transport processes of particulate mercury in modifying marine anthropogenic secondary sources, the case of Haifa bay, Israel. AB - We have assessed the redistribution of a secondary source of sedimentary anthropogenic mercury in the Haifa bay (HB) area (SE Levantine basin), which is the northern sink for Nile-driven sand. A long-term (30years) ~80% decrease of the total sedimentary mercury concentrations (THg) was recorded in the inner bay, while an up to 3-fold increase was recorded in the top sediments of the outer bay. Sedimentary THg depth profiles and their temporal variability were used to model the main re-distribution processes, mainly resuspension associated with winter storm-derived transport. This mechanism transforms a secondary, sandy and well-aerated sink into a tertiary, more silty and hypoxic source at adjacent peripheral areas, affecting mercury bioavailability. We revisited the concept of environmental relaxation, i.e. the rate of return of a polluted environment to an acceptable state, showing that sedimentary transport processes may affect the associated ecological risks, mainly at shallow-water coastal sites. PMID- 26892201 TI - Spatial distribution and sources of polychlorinated biphenyls in surface sediments from the Zhoushan Archipelago and Xiangshan Harbor, East China Sea. AB - This study investigated ambient concentrations and potential sources of polychlorinated biphenyls (PCBs) in surface sediments from the Zhoushan Archipelago and adjacent Xiangshan Harbor. The ?18PCB (total 18 PCB) concentrations ranged between 1.48 and 7.94ng/g d.w., average at 4.20ng/g d.w., presenting a low adverse environmental risk. Penta-CB was the dominant congener, contributing 46.01%-86.44% of the total PCBs. Concentrations of PCBs were highest in the northeastern part of the Zhoushan Archipelago and Xiangshan Harbor. Principal component analysis (PCA) showed that PCBs have a mixed origin; atmospheric deposition and PCB dispersion from paint flakings being the main sources of PCB pollution. Aroclor 1245 and Clophen A50 were the potential PCB sources in all sampling sites. This paper provides the first intensive survey and statistical analyses of PCB distributions and sources in the Zhoushan Archipelago and adjacent Xiangshan Harbor. This study may provide a reference to environmental protection and monitoring of PCB pollution in the East China Sea. PMID- 26892202 TI - Variation in macrofaunal communities of sea grass beds along a pollution gradient in Bolinao, northwestern Philippines. AB - This study examined the variation of macrofaunal communities in sea grass beds along a pollution gradient in Bolinao, northwestern Philippines. We established four stations and compared the diversity and abundance of macrofauna between them. The Shannon diversity index in the least polluted station was more than twice higher than that in the most polluted one. Abundance was more than thrice higher in the most polluted station. The species composition generally varied, with community difference explained largely by the predominance of the filter feeding bivalve Gafrarium pectinatum and polychaete Capitella capitata. Species heterogeneity was reduced along the pollution gradient by approximately 19% from the least polluted to the most polluted station. This reduction indicates biodiversity alteration, which has a significant impact on ecosystem functioning. Aspects of species heterogeneity should be considered in environmental impact assessments and the management of coastal areas encountered with anthropogenic disturbances. PMID- 26892204 TI - Spatial variability and response to anthropogenic pressures of assemblages dominated by a habitat forming seaweed sensitive to pollution (northern coast of Alboran Sea). AB - The Cystoseira ericaefolia group is conformed by three species: C. tamariscifolia, C. mediterranea and C. amentacea. These species are among the most important habitat forming species of the upper sublittoral rocky shores of the Mediterranean Sea and adjacent Atlantic coast. This species group is sensitive to human pressures and therefore is currently suffering important losses. This study aimed to assess the influence of anthropogenic pressures, oceanographic conditions and local spatial variability in assemblages dominated by C. ericaefolia in the Alboran Sea. The results showed the absence of significant effects of anthropogenic pressures or its interactions with environmental conditions in the Cystoseira assemblages. This fact was attributed to the high spatial variability, which is most probably masking the impact of anthropogenic pressures. The results also showed that most of the variability occurred on at local levels. A relevant spatial variability was observed at regional level, suggesting a key role of oceanographic features in these assemblages. PMID- 26892203 TI - Wave energy level and geographic setting correlate with Florida beach water quality. AB - Many recreational beaches suffer from elevated levels of microorganisms, resulting in beach advisories and closures due to lack of compliance with Environmental Protection Agency guidelines. We conducted the first statewide beach water quality assessment by analyzing decadal records of fecal indicator bacteria (enterococci and fecal coliform) levels at 262 Florida beaches. The objectives were to depict synoptic patterns of beach water quality exceedance along the entire Florida shoreline and to evaluate their relationships with wave condition and geographic location. Percent exceedances based on enterococci and fecal coliform were negatively correlated with both long-term mean wave energy and beach slope. Also, Gulf of Mexico beaches exceeded the thresholds significantly more than Atlantic Ocean ones, perhaps partially due to the lower wave energy. A possible linkage between wave energy level and water quality is beach sand, a pervasive nonpoint source that tends to harbor more bacteria in the low-wave-energy environment. PMID- 26892205 TI - Using an integrated approach to assess the sediment quality of an estuary from the semi-arid coast of Brazil. AB - The Jundiai-Potengi Estuary (JPE) on the semi-arid coast of Brazil is influenced by multiple sources of pollution. Sediment quality at 10 JPE sites was evaluated through an integrated approach. Rainy and dry seasons were considered. Collected sediments were analyzed for texture, metal, nitrogen, phosphorus concentrations, and toxicity to invertebrates. Geochemical and ecotoxicological data were integrated using qualitative approaches and multivariate techniques. We observed decreased sediment quality in both seasons, particularly in the mid-estuary. In the dry season, the contamination-toxicity relationship was clearer, as hydrological conditions favor contaminant retention within the estuary. Rainy season conditions were found to be worse, since stormwater drainage from agricultural and urban areas carries the contamination into the estuary. Because of the contamination sources and dissolved and particle-bound metal transport, contamination and toxicity did not correlate as clearly in the rainy season. The results suggest that unmeasured contaminants are contributing to JPE sediment degradation. PMID- 26892207 TI - Is It Time to Share Pediatric Guideline Development? PMID- 26892206 TI - Vital Autotransplantation and Orthodontic Treatment of a Transmigrant Mandibular Canine. AB - The purpose of this study was to present the case of a 14-year-old patient with an apically closed, transmigrated permanent canine that was autotransplanted into its natural position without endodontic treatment and orthodontically aligned into ideal occlusion. The transplanted canine maintained long-term tooth vitality, physiologic mobility, and normal masticatory function. Also discussed are the clinical considerations and rationale behind this treatment, the clinical procedure, and factors for successully implementing this alternative approach in managing this relatively common developmental dental anomaly. PMID- 26892208 TI - Letter to the Editor. PMID- 26892209 TI - Letter to the Editor. PMID- 26892210 TI - Survival Rate of Atraumatic Restorative Treatment (ART) Restorations Using a Glass Ionomer Bilayer Technique with a Nanofilled Coating: A Bi-center Randomized Clinical Trial. AB - PURPOSE: The high-viscosity consistency of glass ionomer cement (GIC) contributes to its inappropriate adaptation, while the material's premature exposure to humidity decreases its mechanical properties. This study's purposes were to: (1) investigate approximal atraumatic restorative treatment (ART) restorations' survival in primary molars using two different insertion techniques and two surface protection materials; and (2) compare the results of cities where treatments were performed. METHODS: A total of 389 six- to seven-year-olds were selected from two cities in Brazil and randomly assigned into four groups: (1) ART restorations plus petroleum jelly (PJ); (2) bilayer-ART restorations plus PJ; (3) ART restorations plus nanofilled coating for GIC (NC); (4) bilayer-ART restorations plus NC. Restorations were evaluated after one, six, 12, 18, and 24 months. Kaplan-Meier survival analysis, log-rank test, and Cox regression analysis were performed. RESULTS: Restorations' cumulative survival was 46.4 percent. There was a higher survival of bilayer-ART restorations (P=0.03). No difference was observed between surface protection materials (P=0.57). Restorations made in Barueri were almost 2.5-fold more likely to survive than those from Recife (P<0.001). CONCLUSIONS: The bilayer technique improves approximal ART restorations' survival in primary molars. The nanofilled coating does not influence restorations' survival rate, and the city where treatments were performed influences restoration survival. PMID- 26892211 TI - Double-Blind Crossover Study to Compare Pain Experience During Inferior Alveolar Nerve Block Administration Using Buffered Two Percent Lidocaine in Children. AB - PURPOSE: Buffering of anesthetic solutions has been suggested to reduce pain on injection and onset of anesthesia. The purpose of this study was to assess the reduction in pain on injection during inferior alveolar nerve block administration in children. METHODS: A double blind crossover study was designed where 30 six- to 12-year-old patients received two sessions of inferior alveolar nerve block scheduled one week apart. Two percent lidocaine with 1:200,000 epinephrine was given during one appointment, and a buffered solution was given during the other. Pain on injection was assessed using the sound, eye, and motor (SEM) scale, and the time to onset was assessed after gingival probing. The Heft Parker visual analogue scale (HP-VAS) was self recorded by the patient after administration of local anesthesia. RESULTS: When tested using Mann-Whitney analysis, no significant differences were found between the SEM scores (P=0.71) and HP-VAS scores (P=0.93) for the two solutions used. Student's t test was used to assess the difference in the onset of anesthesia, which was also found to be statistically insignificant (P=0.824). CONCLUSION: Buffered lidocaine did not reduce the pain on injection or time to onset of anesthesia for inferior alveolar nerve block in children. PMID- 26892212 TI - Parental Attitudes Toward Advanced Behavior Guidance Techniques Used in Pediatric Dentistry. AB - PURPOSE: To re-examine parental attitudes toward advanced behavior management techniques in pediatric dentistry and determine whether cost, urgency, and amount of treatment influence parental preferences. METHODS: Parents viewed previously validated videotaped clinical vignettes of four advanced behavior guidance techniques: (1) passive immobilization; (2) active immobilization; (3) general anesthesia; and (4) oral sedation. The study was conducted in a children's hospital dental clinic and a suburban private pediatric dentistry office. Parents rated overall acceptance of the techniques, and acceptance under specified conditions using an anchored visual analogue scale. RESULTS: One hundred five parents completed the survey; 55 from the children's hospital and 50 from private practice. Oral sedation was rated as the most acceptable technique, followed by general anesthesia, active immobilization, and passive immobilization. As urgency, convenience, and previous experience increased, parental acceptance of the technique increased. As cost of treatment increased, parental acceptance decreased. Ratings between the children's hospital group and private practice group differed, as did the demographic variables of insurance, income, and race. CONCLUSIONS: The hierarchy of parental acceptance of advanced behavior guidance techniques is changing with increasing approval of pharmacological management and decreasing approval of physical management. The health care delivery system, urgency, convenience, previous experience, and cost all influence parental acceptance. PMID- 26892213 TI - Clinical Evaluation of Conventional Radiography, Radiovisiography, and an Electronic Apex Locator in Determining the Working Length in Primary Teeth. AB - PURPOSE: This study's purposes were to: (1) compare the accuracy of conventional radiography (CR), radiovisiography (RVG), and the Root ZX mini apex locator (EAL) in determining the working length in primary teeth; and (2) determine the effect of wet/dry conditions on the accuracy of the EAL. METHODS: Twenty-two children (six to 15 years old), with 41 root canals of primary teeth with or without resorption indicated for extraction, were selected. CR and RVG were used to determine the working length, followed by EAL, according to the manufacturer's instructions in both dry and wet fields (saline). Following extraction of the teeth, the actual working length was determined under stereo microscope (2X). The data was tabulated and statistically analyzed using one-way analysis of variance and student's t test. RESULTS: The highest percentage of accurate working length measurements within the acceptable range of +/-0.5 mm were for EAL (95.1 percent), followed by RVG (75.6 percent) and CR (75.6 percent). There were no statistically significant differences between the three techniques (P>0.05), and the readings obtained by the apex locator were not affected by resorption or the medium (wet/dry). CONCLUSIONS: The Root ZX mini apex locator showed the most promising results, followed by radiovisiography and conventional radiography. PMID- 26892214 TI - Comparison of Amount of Primary Tooth Reduction Required for Anterior and Posterior Zirconia and Stainless Steel Crowns. AB - PURPOSE: To determine if aggressiveness of primary tooth preparation varied among different brands of zirconia and stainless steel (SSC) crowns. METHODS: One hundred primary typodont teeth were divided into five groups (10 posterior and 10 anterior) and assigned to: Cheng Crowns (CC); EZ Pedo (EZP); Kinder Krowns (KKZ); NuSmile (NSZ); and SSC. Teeth were prepared, and assigned crowns were fitted. Teeth were weighed prior to and after preparation. Weight changes served as a surrogate measure of tooth reduction. RESULTS: Analysis of variance showed a significant difference in tooth reduction among brand/type for both the anterior and posterior. Tukey's honest significant difference test (HSD), when applied to anterior data, revealed that SSCs required significantly less tooth removal compared to the composite of the four zirconia brands, which showed no significant difference among them. Tukey's HSD test, applied to posterior data, revealed that CC required significantly greater removal of crown structure, while EZP, KKZ, and NSZ were statistically equivalent, and SSCs required significantly less removal. CONCLUSIONS: Zirconia crowns required more tooth reduction than stainless steel crowns for primary anterior and posterior teeth. Tooth reduction for anterior zirconia crowns was equivalent among brands. For posterior teeth, reduction for three brands (EZ Pedo, Kinder Krowns, NuSmile) did not differ, while Cheng Crowns required more reduction. PMID- 26892216 TI - Dental Visits by Age One: General Dentist Availability for Privately Insured Children in a Rural State. AB - PURPOSE: To evaluate the availability of general dentists who treat very young children with private insurance in the context of recommendations for age one dental visit. METHODS: Administrative data from Delta Dental of Iowa were analyzed to identify general dentists providing care to children younger than 18 years old in 2005 and 2012. Characteristics of dentists providing care to children younger than two years old were compared, examining changes over time. Geographical distribution of dentists who treated children younger than two years old was examined. RESULTS: The proportion of dentists treating children younger than two years old increased from six percent in 2005 to 18 percent in 2012. Younger dentists, females, graduates of The University of Iowa College of Dentistry, and those in metropolitan locations were significantly more likely to treat children younger than two years old. Fifty-one of 99 counties lacked any dentists who had provided care to privately insured children younger than two years old. CONCLUSIONS: The proportion of dentists in Iowa treating privately insured children younger than two years old has increased since 2005. However, relatively few general dentists provided care to very young children when compared to previous survey-based figures. Geographic distribution of providers supports the hypothesis that provider availability may pose a barrier to early dental visits. PMID- 26892218 TI - Caries Experience in Individuals with Moebius Syndrome. AB - PURPOSE: Moebius syndrome (MS) is a rare congenital facial diplegia characterized by partial or complete sixth and seventh cranial nerve palsy. Orofacial manifestations include micrognathia, increased overbite, high arched palate, morphological changes in the tongue, and dental crowding. Case reports and small case series have shown a high prevalence of caries in MS patients. The purpose of this study was to compare the prevalence of caries between individuals with Moebius syndrome and controls using the International Caries Detection and Assessment System (ICDAS). METHODS: A total of 90 participants were divided into two groups: (1) the study group, comprising 34 individuals with MS; and (2) the control group, comprising 56 age- and gender-matched healthy subjects without MS. All individuals were evaluated for the presence of caries using the ICDAS. For statistical analysis, different ICDAS scores were used as cutoff points. RESULTS: The number of carious lesions in the MS group was higher only for early-stage caries (i.e., ICDAS scores of 1 and 2; 27.0+/-23.0 versus 16.0+/-14.1 and 26.3+/ 23.2 versus 15.2+/-13.6, respectively). CONCLUSION: Moebius syndrome patients have more early carious lesions than controls without the syndrome. PMID- 26892217 TI - Maryland Physicians' Knowledge, Opinions, and Practices Related to Dental Caries Etiology and Prevention in Children. AB - PURPOSE: The purpose of this study was to assess Maryland physicians' knowledge and understanding of dental caries etiology and prevention, opinions related to prevention effectiveness, and their prevention practices. METHODS: In 2010, a 30 item, self-administered survey questionnaire was mailed to a random sample of 1,472 Maryland family physicians and pediatricians, with 294 surveys being returned and usable, yielding a 20 percent return rate. Statistical analyses in this descriptive study included distributions and cross-tabulations for the survey responses. RESULTS: Thirty-five percent of family physicians and 45 percent of pediatricians indicated they provide caries prevention education to their patients. Approximately half of the physicians reported performing some type of caries risk assessment. Out of 10 dental caries knowledge questions, there was not a single question that the majority of physicians answered correctly with certainty. Nine percent of family physicians and 12 percent of pediatricians reported they provided fluoride varnish treatment to their three- to six-year-old patients at the time of this survey. CONCLUSIONS: This study identified specific areas, related to Maryland physicians' dental caries etiology and prevention knowledge, that continuing education and training programs could enhance. PMID- 26892215 TI - Validation and Impact of Caregivers' Oral Health Knowledge and Behavior on Children's Oral Health Status. AB - PURPOSE: To validate oral health knowledge and behavior measures from the Basic Research Factors Questionnaire, developed to capture specific themes contributing to children's oral health outcomes and the influence of caregivers. METHODS: Data were collected as part of a randomized clinical trial (n equals 992) aimed at reducing dental caries in young children. Participants were American Indian/Alaska Native caregivers with a three- to five-year-old child enrolled in a Navajo Nation Head Start Center. Caregivers completed the questionnaire at enrollment with concomitant evaluation of children for decayed, missing, and filled tooth surfaces (dmfs). Oral health knowledge and behavior outcomes were compared with convergent measures (participant sociodemographic characteristics, oral health attitudes, and indicators of oral health status). RESULTS: Caregiver oral health knowledge was significantly associated with education, income, oral health behavior, and all but one of the oral health attitude measures. Behavior was significantly associated with several measures of oral health attitudes and all but one measure of oral health status. As the behavior score improved, dmfs scores declined, child/caregiver overall oral health status improved, and pediatric oral health quality of life improved. CONCLUSIONS: Questionnaire measures were valid for predicting specific caregiver factors potentially contributing to children's oral health status. PMID- 26892219 TI - Recent conjugation strategies of small organic fluorophores and ligands for cancer-specific bioimaging. AB - Conjugation between various small fluorophores and specific ligands has become one of the main strategies for bioimaging in disease diagnosis, medicinal chemistry, immunology, and fluorescence-guided surgery, etc. Herein, we present our review of recent studies relating to molecular fluorescent imaging techniques for various cancers in cell-based and animal-based models. Various organic fluorophores, especially near-infrared (NIR) probes, have been employed with specific ligands. Types of ligands used were small molecules, peptides, antibodies, and aptamers; each has specific affinities for cellular receptor proteins, cancer-specific antigens, enzymes, and nucleic acids. This review can aid in the selection of cancer-specific ligands and fluorophores, and may inspire the further development of new conjugation strategies in various cellular and animal models. PMID- 26892221 TI - Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation. AB - Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. PMID- 26892220 TI - Carboxylesterases: General detoxifying enzymes. AB - Carboxylesterases (CE) are members of the esterase family of enzymes, and as their name suggests, they are responsible for the hydrolysis of carboxylesters into the corresponding alcohol and carboxylic acid. To date, no endogenous CE substrates have been identified and as such, these proteins are thought to act as a mechanism to detoxify ester-containing xenobiotics. As a consequence, they are expressed in tissues that might be exposed to such agents (lung and gut epithelia, liver, kidney, etc.). CEs demonstrate very broad substrate specificities and can hydrolyze compounds as diverse as cocaine, oseltamivir (Tamiflu), permethrin and irinotecan. In addition, these enzymes are irreversibly inhibited by organophosphates such as Sarin and Tabun. In this overview, we will compare and contrast the two human enzymes that have been characterized, and evaluate the biology of the interaction of these proteins with organophosphates (principally nerve agents). PMID- 26892222 TI - Economic burden of underweight and overweight among adults in the Asia-Pacific region: a systematic review. AB - OBJECTIVE: To assess the economic burden of underweight and overweight among adults in the Asia-Pacific region. METHOD: Systematic review of articles published until March 2015. RESULTS: Seventeen suitable articles were found, of which 13 assess the economic burden of overweight/obesity and estimate that it accounts for 1.5-9.9% of a country's total healthcare expenditure. Four articles on the economic burden of underweight estimate it at 2.5-3.8% of the country's total GDP. Using hospital data, and compared to normal weight individuals, four articles estimated extra healthcare costs for overweight individuals of 7-9.8% and more, and extra healthcare costs for obese individuals of 17-22.3% and higher. CONCLUSION: Despite methodological diversity across the studies, there is a consensus that both underweight and overweight impose a substantial financial burden on healthcare systems in the Asia-Pacific region. PMID- 26892223 TI - Adhesion of Pseudomonas fluorescens biofilms to glass, stainless steel and cellulose. AB - OBJECTIVES: The adhesion of colloidal probes of stainless steel, glass and cellulose to Pseudomonas fluorescens biofilms was examined using atomic force microscopy (AFM) to allow comparisons between surfaces to which biofilms might adhere. RESULTS: Biofilm was grown on a stainless steel substrate and covered most of the surface after 96 h. AFM approach and retraction curves were obtained when the biofilm was immersed in a tryptone/soy medium. On approach, all the colloidal probes experienced a long non-contact phase more than 100 nm in length, possibly due to the steric repulsion by extracellular polymers from the biofilm and hydrophobic effects. Retraction data showed that the adhesion varied from position to position on the biofilm. The mean value of adhesion of glass to the biofilm (48 +/- 7 nN) was the greatest, followed by stainless steel (30 +/- 7 nN) and cellulose (7.8 +/- 0.4 nN). CONCLUSION: The method allows understanding of adhesion between the three materials and biofilm, and development of a better strategy to remove the biofilm from these surfaces relevant to different industrial applications. PMID- 26892224 TI - Determination of glutathione in apoptotic SMMC-7221 cells induced by xylitol selenite using capillary electrophoresis. AB - OBJECTIVE: To determine the glutathione (GSH) content in a human hepatoma cell line (SMMC-7221) treated with xylitol/selenite, providing a part of an investigation of its anti-cancer mechanisms. RESULTS: The nuclei of SMMC-7221 cells were stained with Hoechst 33258 in an apoptosis assay, and their morphology subsequently changed from circular to crescent shape. The calibration curve (r(2) = 0.992) was established, and GSH content markedly decreased after treated with 0.5 and 1 mg xylitol/selenite l(-1) for 12, 36 and 60 h (12 h: from 95.57 +/- 19.57 to 29.09 +/- 7.74 and 24.27 +/- 11.15; 36 h: from 70.73 +/- 11.35 to 19.54 +/- 6.39 and 9.35 +/- 6.69; 60 h: from 72.63 +/- 16.94 to 7.432 +/- 3.84 and 0). The depletion rate of GSH was more related to the concentration of xylitol/selenite than the treatment time (from 69.95 +/- 1.87 to 100 % vs. 0.22 +/- 0.2 to 100 %). CONCLUSIONS: Xylitol/selenite is a promising anti-cancer drug to induce apoptosis in SMMC-7221 cells. It may regulate the apoptosis through the co-action of multiple mechanisms related to GSH depletion. PMID- 26892225 TI - Improved delivery of Cas9 protein/gRNA complexes using lipofectamine CRISPRMAX. AB - OBJECTIVES: To identify the best lipid nanoparticles for delivery of purified Cas9 protein and gRNA complexes (Cas9 RNPs) into mammalian cells and to establish the optimal conditions for transfection. RESULTS: Using a systematic approach, we screened 60 transfection reagents using six commonly-used mammalian cell lines and identified a novel transfection reagent (named Lipofectamine CRISPRMAX). Based on statistical analysis, the genome modification efficiencies in Lipofectamine CRISPRMAX-transfected cell lines were 40 or 15 % higher than those in Lipofectamine 3000 or RNAiMAX-transfected cell lines, respectively. Upon optimization of transfection conditions, we observed 85, 75 or 55 % genome editing efficiencies in HEK293FT cells, mouse ES cells, or human iPSCs, respectively. Furthermore, we were able to co-deliver donor DNA with Cas9 RNPs into a disrupted EmGFP stable cell line, resulting in the generation of up to 17 % EmGFP-positive cells. CONCLUSION: Lipofectamine CRISPRMAX was characterized as the best lipid nanoparticles for the delivery of Cas9 RNPs into a variety of mammalian cell lines, including mouse ES cells and iPSCs. PMID- 26892226 TI - Advanced mechanical circulatory support for post-cardiotomy cardiogenic shock: a 20-year outcome analysis in a non-transplant unit. AB - BACKGROUND: Post-cardiotomy cardiogenic shock (PCCS) has an incidence of 2-6 % after routine adult cardiac surgery. 0.5-1.5 % are refractory to inotropic and intra-aortic balloon pump (IABP) support. Advanced mechanical circulatory support (AMCS) can be used to salvage carefully selected number of such patients. High costs and major complication rates have lead to centralization and limited funding for such devices in the UK. We have looked the outcomes of such devices in a non-transplant, intermediate-size adult cardiothoracic surgery unit. METHODS: Inclusion criteria included any adult patient who had received salvage veno-arterial extra-corporeal membrane oxygenation (V-A ECMO) or a ventricular assist device (VAD) for PCCS refractory to IABP and inotropic support following cardiac surgery from April 1995-April 2015. RESULTS: Sixteen patients met the inclusion criteria. Age range was 34-83 years (median 71). There was a male predominance of 12 (75 %). Overall, 15 (94 %) had received ECMO of which, 10 (67 %) had received central ECMO and 5 (33 %) had received peripheral ECMO. One patient (6 %) had a VAD. The most common complication was haemorrhage. Stroke, femoral artery pseudo-aneurysm, sepsis and renal failure also occurred. Thirty day survival was 37.5 %. Survival rate to hospital discharge was 31.2 %. All survivors had NYHA class I-II at 24 months follow-up. CONCLUSIONS: Our survival rate is similar to that reported in several previous studies. However, the use of AMCS for refractory PCCS is associated with serious complications. The survivors in our cohort appear to maintain an acceptable quality of life. PMID- 26892227 TI - The effect of capacitively coupled (CC) electrical stimulation on human disc nucleus pulposus cells and the relationship between CC and BMP-7. AB - PURPOSE: An in vitro study using human intervertebral disc nucleus pulposus cells to evaluate the effects of CC stimulation on disc-matrix macromolecule production. METHODS: Nucleus pulposus cells were cultured in alginate beads and treated with CC stimulation. The effect of BMP on CC stimulation of the cells was evaluated by applying a BMP blocker (noggin) or by applying additional BMP-7 to the culture. The mRNA levels of the disc extracellular matrix genes (collagen I, II, aggrecan) and BMPs were measured by real-time PCR. The protein levels of aggrecan, collagen II, and BMPs were determined by ELISAs and Western blots. Sulfated glycosaminoglycan (sGAG) content was assayed using the DMMB method. RESULTS: (1) CC stimulation upregulates the production of the disc-matrix macromolecular components: sGAG, aggrecan and collagen II; (2) CC stimulation increases the ratio of mRNA expression levels of collagen II to collagen I; (3) CC stimulation induces the expression of endogenous BMP-4 and BMP-7; (4) inhibition of BMP activity (using noggin) reduces CC-mediated upregulation of aggrecan and collagen II; (5) CC and BMP-7 act in synergy to increase the upregulation of disc-matrix macromolecules. CONCLUSION: CC stimulation upregulates the production of the intervertebral disc-matrix macromolecules aggrecan, collagen II, and sGAG by a mechanism involving BMPs. CC stimulation acts in synergy with BMP-7 to increase the upregulation of these disc-matrix macromolecules. PMID- 26892228 TI - Learning changes the attentional status of prospective memories. AB - Objects in visual working memory (VWM) that are only prospectively relevant can nevertheless affect the guidance of attention in an ongoing visual search task. Here we investigated whether learning changes the attentional status of such prospective memories. Observers performed a visual search while holding an item in memory for a later memory test. This prospective memory was then repeated for several trials. When the memory was new, it interfered with the ongoing search task. However, with repetition, memory performance increased but memory-based interference rapidly diminished, suggesting that observers learned to shield the prospective memory from the ongoing task. This contrasts with earlier findings showing stronger attentional biases from learned memories when these are immediately task-relevant. Interestingly, interference resurfaced again in anticipation of a new memory, suggesting a reactivation of VWM. These effects were sensitive to task context, indicating that the attentional status of prospective memories is flexible. PMID- 26892230 TI - The preventative effect of Akt knockout on liver cancer through modulating NF kappaB-regulated inflammation and Bad-related apoptosis signaling pathway. AB - Primary liver cancer is globally the sixth most frequent cancer, and the second leading cause of cancer death and its incidence is increasing in many countries, thus, becoming serious threat to human health. Substantial research has focused on the treatment and prevention of liver cancer. However, the underlying molecular mechanism of liver cancer are still not fully understood, and therefore development of treatments are delayed. Akt has been suggested to play an essential role in the progression of inflammation response and apoptosis. Hence, in the present study, Akt knockout mice and cell lines were used as a model to investigate the molecular mechanism of Akt-associated inflammatory and apoptotic signaling pathway with NF-kappaB and Bad in the progression of liver cancer. Western blotting, quantitative RT-PCR (qRT-PCR), immunohistochemistry, ELISA and flow cytometric analysis were used to determine the key signaling pathway in the development of liver cancer. The results indicated that, compared to the normal liver cells, the expression of Akt was significantly higher in liver cancer cell lines. In addition, Akt-knockout liver cancer cells showed lower Akt expression. we also, found that Akt-knockout cancer cell lines modulated inflammation response and apoptosis via inhibiting NF-kappaB expression and suppressing apoptotic activation. Our results indicated that the downstream signals, including cytokines regulated by NF-kappaB signaling pathway and caspase-3 activated apoptosis affected by Bad were downregulated for knockout of Akt. These findings demonstrated that Akt is related to NF-kappaB and Bad signaling pathway possibly playing a direct role in the progression of liver cancer. Thus, Akt might be an important and potential treatment choice for the clinical diagnosis and treatment in the future. PMID- 26892229 TI - Efficacy and Safety of rAAV2-ND4 Treatment for Leber's Hereditary Optic Neuropathy. AB - Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited disease leading to blindness. A mitochondrial DNA point mutation at the 11778 nucleotide site of the NADH dehydrogenase subunit 4 (ND4) gene is the most common cause. The aim of this study was to evaluate the efficacy and safety of a recombinant adeno associated virus 2 (AAV2) carrying ND4 (rAAV2-ND4) in LHON patients carrying the G11778A mutation. Nine patients were administered rAAV2-ND4 by intravitreal injection to one eye and then followed for 9 months. Ophthalmologic examinations of visual acuity, visual field, and optical coherence tomography were performed. Physical examinations included routine blood and urine. The visual acuity of the injected eyes of six patients improved by at least 0.3 log MAR after 9 months of follow-up. In these six patients, the visual field was enlarged but the retinal nerve fibre layer remained relatively stable. No other outcome measure was significantly changed. None of the nine patients had local or systemic adverse events related to the vector during the 9-month follow-up period. These findings support the feasible use of gene therapy for LHON. PMID- 26892231 TI - Detection of Treponema pallidum Sp. Pallidum DNA in Cerebrospinal Fluid (CSF) by Two PCR Techniques. AB - BACKGROUND: Laboratory diagnosis of neurosyphilis is complicated especially when it is asymptomatic, no single laboratory test result being appropriate to diagnose central nervous system infectivity caused by Treponema pallidum. Our objective was to evaluate two polymerase chain reaction (PCR) techniques for the detection of T. pallidum DNA in the cerebrospinal fluid (CSF) of patients with syphilis. METHODS: One hundred twenty-four CSF samples from patients with reactive blood tests for syphilis were obtained. Two PCR techniques (47-PCR, polA PCR) were used to detect T. pallidum DNA. The laboratory criteria used for the diagnosis of neurosyphilis to which the PCR techniques were compared were those recommended by the IUSTI: 2008 European guidelines on the management of syphilis. RESULTS: Treponema pallidum DNA was detected amplified in 37 of 124 (29.8%) and 30 of 124 (24.2%) samples with the 47-PCR and polA-PCR, respectively. Sensitivities were 75.8% and 69.7% and specificities 86.8% and 92.3%, respectively, for 47-PCR and polA-PCR techniques, respectively. The three CSF samples of patients with primary syphilis did not fulfill the criteria of neurosyphilis and DNA was only detected in one by the 47-PCR. In samples from secondary syphilis and neurosyphilis, three of nine and nine of nine respectively, results were coincident for the two PCR techniques and neurosyphilis criteria. Major discrepancies between the two PCR techniques and neurosyphilis diagnostic criteria were observed in latent syphilis. CONCLUSION: Beyond some limitations of the study, which are discussed here, both PCR techniques seem to be useful for the diagnosis of neurosyphilis, although 47-PCR presents a higher sensitivity and polA-PCR a higher specificity. PMID- 26892234 TI - Capillary interaction of microspheres with pinned boundary conditions: a clarification. AB - It is the aim of this short note to point out that a quadratic contribution in the deviatoric curvature to the capillary interaction of microspheres with pinned contact lines is indeed compatible with the experimental measurements, in contrast to what has been reported in N. Sharifi-Mood, I. B. Liu and K. J. Stebe, Soft Matter, 2016, 12, 333. PMID- 26892232 TI - Challenging immunosuppression treatment in lung transplant recipients with kidney failure. AB - Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results. PMID- 26892233 TI - Characterization of tau positron emission tomography tracer [18F]AV-1451 binding to postmortem tissue in Alzheimer's disease, primary tauopathies, and other dementias. AB - INTRODUCTION: Aggregation of tau is a hallmark of many neurodegenerative diseases, and tau imaging with positron emission tomography (PET) may allow early diagnosis and treatment monitoring. We assessed binding of the PET tracer [18F]AV 1451 in a range of dementias. METHODS: Phosphorimaging was used to quantify binding to postmortem brain tissue from 33 patients with different, histopathologically characterized, neurodegenerative dementias. RESULTS: [18F]AV 1451 showed high specific binding in cases with Alzheimer's disease (AD), moderate binding in Pick's disease and frontotemporal dementia with parkinsonism 17, and low but displaceable binding in corticobasal degeneration, progressive supranuclear palsy, non-tau proteinopathies, and in controls without pathology. Tracer binding did not correlate with tau load within disease groups. DISCUSSION: [18F]AV-1451 binds to tau in AD, and some other tauopathies. However, evidence for a non-tau binding site and lack of correlation between tracer binding and antibody staining suggest that reliable quantification of tau load with this tracer is problematic. PMID- 26892236 TI - Co-expression networks in generation of induced pluripotent stem cells. AB - We developed an adenoviral vector, in which Yamanaka's four reprogramming factors (RFs) were controlled by individual CMV promoters in a single cassette (Ad SOcMK). This permitted coordinated expression of RFs (SOX2, OCT3/4, c-MYC and KLF4) in a cell for a transient period of time, synchronizing the reprogramming process with the majority of transduced cells assuming induced pluripotent stem cell (iPSC)-like characteristics as early as three days post-transduction. These reprogrammed cells resembled human embryonic stem cells (ESCs) with regard to morphology, biomarker expression, and could be differentiated into cells of the germ layers in vitro and in vivo. These iPSC-like cells, however, failed to expand into larger iPSC colonies. The short and synchronized reprogramming process allowed us to study global transcription changes within short time intervals. Weighted gene co-expression network analysis (WGCNA) identified sixteen large gene co-expression modules, each including members of gene ontology categories involved in cell differentiation and development. In particular, the brown module contained a significant number of ESC marker genes, whereas the turquoise module contained cell-cycle-related genes that were downregulated in contrast to upregulation in human ESCs. Strong coordinated expression of all four RFs via adenoviral transduction may constrain stochastic processes and lead to silencing of genes important for cellular proliferation. PMID- 26892235 TI - Type I Interferon Regulates the Placental Inflammatory Response to Bacteria and is Targeted by Virus: Mechanism of Polymicrobial Infection-Induced Preterm Birth. AB - PROBLEM: Preterm birth (PTB) affects approximately 12% of pregnancies and at least 50% of cases have no known risk factors. We hypothesize that subclinical viral infections of the placenta are a factor sensitizing women to intrauterine bacterial infection. Specifically, we propose that viral-induced placental IFN beta inhibition results in a robust inflammatory response to low concentrations of bacteria. METHODS: Human trophoblast SW.71, C57BL/6, and interferon (IFN) receptor knockout animals were used to determine IFN function. Illumina and Bio Rad microarrays identified pathways. RESULTS: Inhibiting the IFN-beta pathway resulted in a significant increase in inflammatory cytokines such as IL-1B in response to LPS. Twist was positively correlated with IFN-beta expression and STAT3 phosphorylation and overexpressing Twist reduced IL-1B. Treating IFNAR-/- mice with low-dose LPS at E15.5 caused preterm birth. CONCLUSION: IFN-beta was identified as a key modulator of placental inflammation and, importantly, is commonly affected by viruses. We propose dysregulation of IFN-beta is a major determinant for preterm birth associated with polymicrobial infection. PMID- 26892237 TI - Genetic basis of hindlimb loss in a naturally occurring vertebrate model. AB - Here we genetically characterise pelvic finless, a naturally occurring model of hindlimb loss in zebrafish that lacks pelvic fin structures, which are homologous to tetrapod hindlimbs, but displays no other abnormalities. Using a hybrid positional cloning and next generation sequencing approach, we identified mutations in the nuclear localisation signal (NLS) of T-box transcription factor 4 (Tbx4) that impair nuclear localisation of the protein, resulting in altered gene expression patterns during pelvic fin development and the failure of pelvic fin development. Using a TALEN-induced tbx4 knockout allele we confirm that mutations within the Tbx4 NLS (A78V; G79A) are sufficient to disrupt pelvic fin development. By combining histological, genetic, and cellular approaches we show that the hindlimb initiation gene tbx4 has an evolutionarily conserved, essential role in pelvic fin development. In addition, our novel viable model of hindlimb deficiency is likely to facilitate the elucidation of the detailed molecular mechanisms through which Tbx4 functions during pelvic fin and hindlimb development. PMID- 26892238 TI - Analysis of coelom development in the sea urchin Holopneustes purpurescens yielding a deuterostome body plan. AB - An analysis of early coelom development in the echinoid Holopneustes purpurescens yields a deuterostome body plan that explains the disparity between the pentameral plan of echinoderms and the bilateral plans of chordates and hemichordates, the three major phyla of the monophyletic deuterostomes. The analysis shows an early separation into a medial hydrocoele and lateral coelomic mesoderm with an enteric channel between them before the hydrocoele forms the pentameral plan of five primary podia. The deuterostome body plan thus has a single axial or medial coelom and a pair of lateral coeloms, all surrounding an enteric channel, the gut channel. Applied to the phyla, the medial coelom is the hydrocoele in echinoderms, the notochord in chordates and the proboscis coelom in hemichordates: the lateral coeloms are the coelomic mesoderm in echinoderms, the paraxial mesoderm in chordates and the lateral coeloms in hemichordates. The plan fits frog and chick development and the echinoderm fossil record, and predicts genes involved in coelomogenesis as the source of deuterostome macroevolution. PMID- 26892239 TI - Anamnestic responses in pigs to the Taenia solium TSOL18 vaccine and implications for control strategies. AB - Specific antibody responses were assessed in pigs immunized with the Taenia solium vaccine TSOL18. Anti-TSOL18 responses were compared 2 weeks after secondary immunization, where the interval between primary and secondary immunization was 4, 8, 12, 16 or 20 weeks. All animals responded to the vaccine and there was no diminution in antibody responses in animals receiving their second injection after an interval up to 20 weeks. Pigs receiving vaccinations at an interval of 12 weeks developed significantly increased antibody responses compared with animals receiving immunizations 4 weeks apart (P = 0.046). The ability to deliver TSOL18 vaccination effectively where the revaccination schedule can be delayed for up to 12-16 weeks in pigs increases the options available for designing T. solium control interventions that incorporate TSOL18 vaccination. PMID- 26892241 TI - Anti-angiogenic therapy (bevacizumab) in the management of oral lichen planus. AB - Oral lichen planus (OLP), a mucocutaneous chronic inflammatory disease, is conventionally managed using topical corticosteroid therapy. Given the fact that OLP is strongly linked to angiogenesis, anti-angiogenic drugs, such as bevacizumab, might be introduced as an alternative treatment for contraindicated, non-responsive patients. The aim of the present study was to report the short term effectiveness and safety of intralesional bevacizumab injection in the management of atrophic/erosive OLP. A case series study was conducted in patients with atrophic/erosive OLP in the buccal mucosa, assigned to receive either 2.5 mg of bevacizumab, by intralesional injection (n = 20, test), or topical 0.1% triamcinolone acetonide ointment (n = 20, control). The size, score, and pain intensity of the lesions were assessed pre- and post-treatment. Tissue biopsies were collected for histopathologic, immunohistochemical, and ultrastructural examination. After 1 wk, the test group had significant reductions both in lesion seize and in pain scores compared with controls. A marked decrease in vascular endothelial growth factor (VEGF) and interleukin-8 immunoexpression was noted in tissue biopsies from bevacizumab-treated lesions compared with control lesions. Furthermore, ultrastructural examination of OLP tissue specimens revealed significant healing signs associated with bevacizumab treatment. Short-term data suggest that intralesional bevacizumab injection effectively and safely achieved resolution of atrophic/erosive OLP lesions without disease exacerbations during a 3-month follow-up period. PMID- 26892240 TI - An Evaluation of Central Sensitization in Patients With Sickle Cell Disease. AB - Central sensitization (CS), nociceptive hyperexcitability known to amplify and maintain clinical pain, has been identified as a leading culprit responsible for maintaining pain in several chronic pain conditions. Recent evidence suggests that it may explain differences in the symptom experience of individuals with sickle cell disease (SCD). Quantitative sensory testing (QST) can be used to examine CS and identify individuals who may have a heightened CS profile. The present study categorized patients with SCD on the basis of QST responses into a high or low CS phenotype and compared these groups according to measures of clinical pain, vaso-occlusive crises, psychosocial factors, and sleep continuity. Eighty-three adult patients with SCD completed QST, questionnaires, and daily sleep and pain diaries over a 3-month period, weekly phone calls for 3 months, and monthly phone calls for 12 months. Patients were divided into CS groups (ie, no/low CS [n = 17] vs high CS [n = 21]), on the basis of thermal and mechanical temporal summation and aftersensations, which were norm-referenced to 47 healthy control subjects. High CS subjects reported more clinical pain, vaso-occlusive crises, catastrophizing, and negative mood, and poorer sleep continuity (Ps < .05) over the 18-month follow-up period. Future analyses should investigate whether psychosocial disturbances and sleep mediate the relationship between CS and pain outcomes. PERSPECTIVE: In general, SCD patients with greater CS had more clinical pain, more crises, worse sleep, and more psychosocial disturbances compared with the low CS group. PMID- 26892242 TI - Genetic spectrum of dyschromatosis symmetrica hereditaria in Chinese patients including a novel nonstop mutation in ADAR1 gene. AB - BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We present a clinical and genetic study of seven unrelated families and two sporadic cases with DSH for mutations in the full coding sequence of ADAR1 gene. METHODS: ADAR1 gene was sequenced in seven unrelated families and two sporadic cases with DSH and 120 controls. Functional significance of the observed ADAR1 mutations was analyzed using PolyPhen 2, SIFT and DDIG-in. RESULTS: We describe six novel mutations of the ADAR1 gene in Chinese patients with DSH including a nonstop mutation p.Stop1227R, which was firstly reported in ADAR1 gene. In silico analysis proves that all the mutations reported here are pathogenic. CONCLUSION: This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH. PMID- 26892243 TI - Effects of agricultural practices on organic matter degradation in ditches. AB - Agricultural practices can result in differences in organic matter (OM) and agricultural chemical inputs in adjacent ditches, but its indirect effects on OM composition and its inherent consequences for ecosystem functioning remain uncertain. This study determined the effect of agricultural practices (dairy farm grasslands and hyacinth bulb fields) on OM degradation by microorganisms and invertebrates with a consumption and food preference experiment in the field and in the laboratory using natural OM collected from the field. Freshly cut grass and hyacinths were also offered to control for OM composition and large- and small mesh-sizes were used to distinguish microbial decomposition and invertebrate consumption. Results show that OM decomposition by microorganisms and consumption by invertebrates was similar throughout the study area, but that OM collected from ditches adjacent grasslands and freshly cut grass and hyacinths were preferred over OM collected from ditches adjacent to a hyacinth bulb field. In the case of OM collected from ditches adjacent hyacinth bulb fields, both microbial decomposition and invertebrate consumption were strongly retarded, likely resulting from sorption and accumulation of pesticides. This outcome illustrates that differences in agricultural practices can, in addition to direct detrimental effects on aquatic organisms, indirectly alter the functioning of adjacent aquatic ecosystems. PMID- 26892244 TI - Genetic diversity of historical Atlantic walruses (Odobenus rosmarus rosmarus) from Bjornoya and Haoya (Tusenoyane), Svalbard, Norway. AB - BACKGROUND: The population size of Atlantic walruses (Odobenus rosmarus rosmarus) is depleted relative to historical abundance levels. In Svalbard, centuries of over-exploitation brought the walrus herds to the verge of extinction, and such bottlenecks may have caused loss of genetic variation. To address this for Svalbard walruses, mitochondrial haplotypes of historical walruses from two major haul-out sites, Bjornoya and Haoya, within the Archipelago were explored using bone samples from animals killed during the peak period of harvesting. RESULTS: Using ancient DNA methodologies, the mitochondrial NADH dehydrogenase 1 (ND1) gene, the cytochrome c oxidase 1 (COI) gene, and the control region (CR) were targeted for 15 specimens from Bjornoya (of which five were entirely negative) and 9 specimens from Haoya (of which one was entirely negative). While ND1 and COI sequences were obtained for only a few samples, the CR delivered the most comprehensive data set, and the average genetic distance among historic Svalbard samples was 0.0028 (SD = 0.0023). CONCLUSIONS: The CR sequences from the historical samples appear to be nested among contemporary Atlantic walruses, and no distinct mitochondrial haplogroups were identified in the historical samples that may have been lost during the periods of extensive hunting. However, given the low sample size and poor phylogenetic resolution it cannot be excluded that such haplogroups existed. PMID- 26892245 TI - Reflex operculoinsular seizures. AB - Activation of specific cortical territories by certain stimuli is known to trigger focal seizures. We report three cases of well documented operculo-insular reflex seizures, triggered by somatosensory stimuli in two and loud noises in the third. Limited operculoinsular resection resulted in an excellent outcome for all. We discuss these observations in regard to the literature on reflex epilepsy and known functions of the insula. [Published with video sequences online]. PMID- 26892247 TI - The state of JTH. PMID- 26892246 TI - Calpain inhibition rescues troponin T3 fragmentation, increases Cav1.1, and enhances skeletal muscle force in aging sedentary mice. AB - Loss of strength in human and animal models of aging can be partially attributed to a well-recognized decrease in muscle mass; however, starting at middle-age, the normalized force (force/muscle cross-sectional area) in the knee extensors and single muscle fibers declines in a curvilinear manner. Strength is lost faster than muscle mass and is a more consistent risk factor for disability and death. Reduced expression of the voltage sensor Ca(2+) channel alpha1 subunit (Cav1.1) with aging leads to excitation-contraction uncoupling, which accounts for a significant fraction of the decrease in skeletal muscle function. We recently reported that in addition to its classical cytoplasmic location, fast skeletal muscle troponin T3 (TnT3) is fragmented in aging mice, and both full length TnT3 (FL-TnT3) and its carboxyl-terminal (CT-TnT3) fragment shuttle to the nucleus. Here, we demonstrate that it regulates transcription of Cacna1s, the gene encoding Cav1.1. Knocking down TnT3 in vivo downregulated Cav1.1. TnT3 downregulation or overexpression decreased or increased, respectively, Cacna1s promoter activity, and the effect was ablated by truncating the TnT3 nuclear localization sequence. Further, we mapped the Cacna1s promoter region and established the consensus sequence for TnT3 binding to Cacna1s promoter. Systemic administration of BDA-410, a specific calpain inhibitor, prevented TnT3 fragmentation, and Cacna1s and Cav1.1 downregulation and improved muscle force generation in sedentary old mice. PMID- 26892249 TI - Beyond (Models of) Disability? AB - The strategy of developing an ontology or models of disability as a prior step to settling ethical issues regarding disabilities is highly problematic for two reasons. First, key definitional aspects of disability are normative and cannot helpfully be made value-neutral. Second, if we accept that the contested concept of disability is value-laden, it is far from obvious that there are definitive reasons for choosing one interpretation of the concept over another. I conclude that the concept of disability is better left ethically open-ended or broad enough to encompass the examination of various ethical issues (such as oppression, minority rights, or physical discomfort). Alternatively, the concept of disability could be altogether abandoned in order to focus on specific issues without being hindered by debates about the nature of disability. Only political costs, rather than conceptual considerations internal to the models, could be weighed against such a conclusion. PMID- 26892250 TI - Influence of initial caries lesions on quality of life in preschool children: a 2 year cohort study. AB - OBJECTIVES: We aimed to assess the impact of the presence of initial and other stages of dental caries on the impairment of oral health-related quality of life in preschool children (COHRQoL) through a cohort study. METHODS: During an epidemiological survey, 478 children (12-59 months old) were examined for dental caries using the International Caries and Detection Assessment System (ICDAS), and their parents answered the Early Childhood Oral Health Impact Scale (ECOHIS). Children were categorized based on the presence of dental caries as follows: children with no caries lesions, children with only initial lesions (ICDAS scores 1 and 2), children with at least one moderate lesion (ICDAS scores 3 and 4) and children with extensive lesions (ICDAS scores 5 and 6). After 2 years, 352 children were re-examined for the presence of dentine cavitations, and their parents completed a new ECOHIS questionnaire. Multilevel Poisson regression analysis was performed to evaluate the impact of the presence of different stages of caries lesions at the baseline on COHRQoL impairment at the follow-up, considering two outcome variables: worsening and severe worsening of COHRQoL. Relative risk values (RR) and respective 95% confidence intervals (95% CI) were calculated. RESULTS: Worsening or severe worsening of the COHRQoL at the follow up were observed only in children with moderate lesions (RR = 2.00; 95% CI = 1.30 3.08 and RR = 2.38; 95% CI = 1.31-4.34, respectively) or children with extensive lesions (RR = 1.59; 95% CI = 1.10-2.30 for worsening and RR = 1.88; 95% CI = 1.13 3.12 for severe worsening). On the other hand, the presence of only initial caries lesions was not a significant predictor of COHRQoL impairment. CONCLUSIONS: The presence of only initial caries lesions does not impair COHRQoL of preschool children; however, moderate and extensive lesions are risk factors for worsening of the COHRQoL. PMID- 26892248 TI - Ethnic Classification in the New Zealand Health Care System. AB - The ethnic or "racial" classification of Maori and non-Maori is a pivotal feature of New Zealand's health system and affects government policy and professional practice within the context of Treaty of Waitangi "partnership" politics. Although intended to empower Maori, ethnic categorization can have unintended and negative consequences by ignoring the causality of material forces in social phenomena. The authors begin by showing how the use of ethnic categories in health policy is justified by the Treaty of Waitangi partnership policies. This provides the context for the argument made in the manuscript that an understanding of the social experience of ethnicity within the complex interaction of sociocultural factors such as socioeconomic location and lifestyle is more useful than using the political construct of ethnic categories in explaining the persistence of low health status for a section of the Maori population. PMID- 26892251 TI - Review of Cardiovascular Imaging in the Journal of Nuclear Cardiology in 2015 Part 2 of 2: Myocardial perfusion imaging. AB - In 2015, the Journal of Nuclear Cardiology ((r)) published many high-quality articles. In this series, we will summarize key articles that have appeared in the Journal last year to provide for the interested reader a quick review of the advancements that have recently occurred in the field. In the first article of this 2-part series, we concentrated on publications dealing with plaque imaging, cardiac positron emission tomography, computed tomography, and magnetic resonance. This review will focus on myocardial perfusion imaging summarizing advances in the field including in diagnosis, prognosis, and appropriate use. PMID- 26892252 TI - Have SPECT artifacts breathed their last? PMID- 26892253 TI - Simple multimodality imaging: An easy, rapid, and inexpensive approach to improve non-invasive test accuracy. PMID- 26892254 TI - Assessment model for the justification of intrusive lifestyle interventions: literature study, reasoning and empirical testing. AB - BACKGROUND: In many countries health insurers, employers and especially governments are increasingly using pressure and coercion to enhance healthier lifestyles. For example by ever higher taxes on cigarettes and alcoholic beverages, and ever stricter smoke-free policies. Such interventions can enhance healthier behaviour, but when they become too intrusive, an unfree society can emerge. Which lifestyle interventions that use pressure or coercion are justifiable and which are not? We tried to develop an assessment model that can be used for answering this question, on a generally acceptable way, for all sorts of lifestyle interventions. METHODS: The intended assessment model was developed in three phases. In the first phase the model was theoretically developed on the basis of literature study and reasoning. In the second phase the model was empirically tested by assessing two detailed cases from everyday practice using the model. The model was improved again and again. In the third phase (publication phase) the 10(th) version of the model was developed while writing this article. RESULTS: An assessment model for the justification of intrusive lifestyle interventions. It comprises three components: (1) 12 assessment criteria (necessity, causality, responsibility, appropriate design, effectiveness, intrusiveness, burdens-benefits-ratio, fairness, support, complementary policies, verifiability, implementation capacity); (2) an assessment structure with three filters (design logic, effects and side effects, implementation); (3) a way of assessing (based on reasonableness and transparency). CONCLUSIONS: We have developed an assessment model for the justification of lifestyle interventions that use pressure or coercion to promote health. The correctness, completeness and practicality of the model are likely. Important principles for the justification are the logic and completeness of the underlying argumentation and the proper use of the available scientific information. Parties for and against a particular intervention could use the model to test and strengthen their argumentation and to improve the quality of the intervention. PMID- 26892255 TI - Tunable integration of absorption-membrane-adsorption for efficiently separating low boiling gas mixtures near normal temperature. AB - Separation of low boiling gas mixtures is widely concerned in process industries. Now their separations heavily rely upon energy-intensive cryogenic processes. Here, we report a pseudo-absorption process for separating low boiling gas mixtures near normal temperature. In this process, absorption-membrane-adsorption is integrated by suspending suitable porous ZIF material in suitable solvent and forming selectively permeable liquid membrane around ZIF particles. Green solvents like water and glycol were used to form ZIF-8 slurry and tune the permeability of liquid membrane surrounding ZIF-8 particles. We found glycol molecules form tighter membrane while water molecules form looser membrane because of the hydrophobicity of ZIF-8. When using mixing solvents composed of glycol and water, the permeability of liquid membrane becomes tunable. It is shown that ZIF-8/water slurry always manifests remarkable higher separation selectivity than solid ZIF-8 and it could be tuned to further enhance the capture of light hydrocarbons by adding suitable quantity of glycol to water. Because of its lower viscosity and higher sorption/desorption rate, tunable ZIF-8/water glycol slurry could be readily used as liquid absorbent to separate different kinds of low boiling gas mixtures by applying a multistage separation process in one traditional absorption tower, especially for the capture of light hydrocarbons. PMID- 26892256 TI - Amperometric Quantification of S-Nitrosoglutathione Using Gold Nanoparticles: A Step toward Determination of S-Nitrosothiols in Plasma. AB - S-Nitrosothiols (RSNOs) are carriers of nitric oxide (NO) and have important biological activities. We propose here the use of gold nanoparticles (AuNPs) and NO-selective amperometric microsensor for the detection and quantification of S nitrosoglutathione (GSNO) as a step toward the determination of plasma RSNOs. AuNPs were used to decompose RSNOs with the quantitative release of free NO which was selectively detected with a NO microsensor. The optimal [GSNO]/[AuNPs] ratio was determined, corresponding to an excess of AuNP surface relative to the molar GSNO amount. Moreover, the influence of free plasma thiols on this method was investigated and a protocol based on the blocking of free thiols with iodoacetic acid, forming the carboxymethyl derivative of the cysteine residues, is proposed. PMID- 26892257 TI - An effective approach for annotation of protein families with low sequence similarity and conserved motifs: identifying GDSL hydrolases across the plant kingdom. AB - BACKGROUND: The massive accumulation of protein sequences arising from the rapid development of high-throughput sequencing, coupled with automatic annotation, results in high levels of incorrect annotations. In this study, we describe an approach to decrease annotation errors of protein families characterized by low overall sequence similarity. The GDSL lipolytic family comprises proteins with multifunctional properties and high potential for pharmaceutical and industrial applications. The number of proteins assigned to this family has increased rapidly over the last few years. In particular, the natural abundance of GDSL enzymes reported recently in plants indicates that they could be a good source of novel GDSL enzymes. We noticed that a significant proportion of annotated sequences lack specific GDSL motif(s) or catalytic residue(s). Here, we applied motif-based sequence analyses to identify enzymes possessing conserved GDSL motifs in selected proteomes across the plant kingdom. RESULTS: Motif-based HMM scanning (Viterbi decoding-VD and posterior decoding-PD) and the here described PD/VD protocol were successfully applied on 12 selected plant proteomes to identify sequences with GDSL motifs. A significant number of identified GDSL sequences were novel. Moreover, our scanning approach successfully detected protein sequences lacking at least one of the essential motifs (171/820) annotated by Pfam profile search (PfamA) as GDSL. Based on these analyses we provide a curated list of GDSL enzymes from the selected plants. CLANS clustering and phylogenetic analysis helped us to gain a better insight into the evolutionary relationship of all identified GDSL sequences. Three novel GDSL subfamilies as well as unreported variations in GDSL motifs were discovered in this study. In addition, analyses of selected proteomes showed a remarkable expansion of GDSL enzymes in the lycophyte, Selaginella moellendorffii. Finally, we provide a general motif-HMM scanner which is easily accessible through the graphical user interface ( http://compbio.math.hr/ ). CONCLUSIONS: Our results show that scanning with a carefully parameterized motif-HMM is an effective approach for annotation of protein families with low sequence similarity and conserved motifs. The results of this study expand current knowledge and provide new insights into the evolution of the large GDSL-lipase family in land plants. PMID- 26892258 TI - High-internal-phase emulsions stabilized by metal-organic frameworks and derivation of ultralight metal-organic aerogels. AB - To design high-internal-phase emulsion (HIPE) systems is of great interest from the viewpoints of both fundamental researches and practical applications. Here we demonstrate for the first time the utilization of metal-organic framework (MOF) for HIPE formation. By stirring the mixture of water, oil and MOF at room temperature, the HIPE stabilized by the assembly of MOF nanocrystals at oil-water interface could be formed. The MOF-stabilized HIPE provides a novel route to produce highly porous metal-organic aerogel (MOA) monolith. After removing the liquids from the MOF-stabilized HIPE, the ultralight MOA with density as low as 0.01 g.cm(-3) was obtained. The HIPE approach for MOA formation has unique advantages and is versatile in producing different kinds of ultralight MOAs with tunable porosities and structures. PMID- 26892259 TI - Noisy galvanic vestibular stimulation enhances spatial memory in cognitive impairment-induced by intracerebroventricular-streptozotocin administration. AB - There are several anatomical connections between vestibular system and brain areas construct spatial memory. Since subliminal noisy galvanic vestibular stimulation (GVS) has been demonstrated to enhance some types of memory, we speculated that application of noisy GVS may improve spatial memory in a rat model of intracerebroventricular streptozotocin (ICV-STZ)-induced cognitive impairment. Moreover, we attempted to determine the effect of repeated exposure to GVS on spatial memory performance. The spatial memory was assessed using Morris water maze test. The groups received 1 (ICV-STZ/GVS-I) or 5 (ICV-STZ/GVS II) sessions, each lasting 30 min, of low amplitude noisy GVS, or no GVS at all (Control, ICV-saline, ICV-STZ/noGVS). Hippocampal morphological changes investigated with cresyl violet staining and the immediate early gene product c Fos, as a neuronal activity marker, was measured. Hippocampal c-Fos positive cells increased in both GVS stimulated groups. We observed significantly improved spatial performance only in ICV-STZ/GVS-II group. Histological evaluation showed normal density in ICV-STZ/GVS-II group whereas degeneration observed in ICV STZ/GVS-I group similar to ICV-STZ/noGVS. The results showed the improvement of memory impairment after repeated exposure to GVS. This effect may be due in part to frequent activation of the vestibular neurons and the hippocampal regions connected to them. Our current study suggests the potential role of GVS as a practical method to combat cognitive decline induced by sporadic Alzheimer disease. PMID- 26892260 TI - High-mobility group AT-hook protein 2 expression and its prognostic significance in MGMT methylated and unmethylated glioblastoma. AB - High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6 methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 +/- 15.7 years, and the median survival was 16 months (SE 2.8; 95% CI, 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean, 0.35; SD, 0.27 vs. 0.03, SD, 0.05) and IHC levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer. PMID- 26892261 TI - Percutaneous CT-guided thermal ablation as salvage therapy for recurrent non small cell lung cancer after external beam radiotherapy: A retrospective study. AB - PURPOSE: The aim of this study was to evaluate radiofrequency ablation (RFA) and microwave ablation (MWA) as a viable salvage option for patients with locally recurrent non-small cell lung cancer (NSCLC) after radiotherapy. MATERIALS AND METHODS: This retrospective study was conducted on patients who had received thermal ablation for recurrent NSCLC post-curative radiotherapy. Medical records and follow-up imaging with computed tomography (CT) and PET-CT were analysed to determine time to local progression (TTLP) and overall survival (OS). TTLP was determined according to the modified RECIST criteria. RESULTS: Twelve patients, mean age 71 +/- 7 years, received 17 thermal ablation sessions, with RFA performed for four lesions and MWA for 13. Nine tumours were squamous cell cancers (SCC) and eight were adenocarcinomas. Eleven tumours had recurred post external beam radiation and one post-stereotactic body radiation therapy. Mean tumour size was 34.2 +/- 12.8 mm, tumour stages prior to radiotherapy were Ia (2), Ib (3), IIa (4), IIb (1) and III (2). Follow-up period was 19 +/- 11 months. Overall median TTLP was 14 months (95% CI: 8, 19), and median OS was 35 months (95% CI: 12, 58). Mean TTLP for tumours <30 mm was 23 months and for tumours >30 mm 14 months (p = 0.20). Recurrence rates reduced from 50% after initial ablation to 20% with a second ablation. Complication rate for pneumothorax requiring intervention was 17%. CONCLUSION: Both RFA and MWA ablation prolonged local tumour control with minimal morbidity in this study group of recurrent NSCLC after radiotherapy. PMID- 26892262 TI - Influence of depression in a sample of people with hallux valgus. AB - Hallux valgus (HV) is a highly-prevalent forefoot deformity associated with progressive subluxation and osteoarthritis of the first metatarsophalangeal joint; it is believed to be associated with depression. The aim of the present study was to determine the association of patients with varying degrees of HV involvement to depression using the Beck Depression Inventory (BDI). The sample consisted of 102 participants (mean age: 45.1 +/- 1.6), who attended an outpatient centre where self-report data were recorded. The degree of HV deformity was determined in both feet, and the scores on the BDI were compared. A total of 38.24% of the sample had depression, with an average BDI score of 10.55 +/- 12.36 points. There was a statistically-significant association between the degree and presence of HV in both feet (P = 0.0001). People with a greater degree of HV deformity in any foot also have a significant increase in depression based on BDI scores, regardless of sex. PMID- 26892263 TI - Near Full-Length Genomic Characterization of a Novel HIV Type 1 CRF01_AE/CRF07_BC Recombinant Form Transmitted Between a Heterosexual Couple in Guangxi, China. AB - In this research, we reported a new second generation recombinant form (GXDY460B) between circulating recombinant form (CRF)01_AE and CRF07_BC in a seroconversion couple who obtained the virus from her husband by heterosexual behavior. The analysis result of the near full-length genomic characterization showed that the genome comprises at least 12 interlaced segments, including six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. Cocirculation of multiple virus subtypes and multiple infection routes have existed for a long time in Guangxi, but the recombinant strain was rarely reported among heterosexual transmission population because of its lower crowd confounding degree than men who have sex with men and injecting drug user population. It is the first time that the unique recombinant form (URF) between CRF01_AE and CRF07_BC was identified among heterosexual transmission in Guangxi. The emergence of the novel recombinant helps to understand the pattern of the URF virus. PMID- 26892264 TI - Comment on: Monitoring treatment practices of childhood asthma in singapore: a questionnaire study. PMID- 26892265 TI - Global analysis of the developmental dynamics of Gossypium hirsutum based on strand-specific transcriptome. AB - Cotton is an economically important crop that provides both natural fiber and by products such as oil and protein. Its global gene expression could provide insight into the biological processes underlying growth and development, which involve suites of genes expressed with temporal and spatial control by regulatory networks. Generally, the goal for cotton breeding is improvement of the fiber; thus, most previous research has focused on identifying genes specific to the fiber. However, seeds may also play an important role in fiber development. In this study, we constructed and systematically analyzed 21 strand-specific RNA-Seq libraries for Gossypium hirsutum, covering different tissues, organs and development stages, from which approximately 970 million reads were generated to provide a global view of gene expression during cotton development. The organ (tissue)-specific gene expression patterns were investigated, providing further insight into the dynamic programming associated with developmental processes and a way to study the coordination of development between fiber cells and ovules. Series of transcription factors and seed-specific genes have been identified as candidate genes that could elucidate key mechanisms and regulatory networks in nutrient accumulation during ovule development and in fiber development. This study reports comprehensive transcriptome dynamics at various stages of cotton development and will serve as a valuable genome-wide transcriptome resource for initial gene discovery and functional characterization of genes in cotton. PMID- 26892266 TI - Usefulness of diffusion-weighted MR imaging for differentiating between benign and malignant superficial soft tissue tumours and tumour-like lesions. AB - OBJECTIVE: To evaluate the usefulness of adding diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping to conventional 3.0-T MRI to differentiate between benign and malignant superficial soft-tissue masses (SSTMs). METHODS: The institutional review board approved this study and informed consent was waived. The authors retrospectively analyzed conventional MR images including diffusion-weighted images (b-values: 0, 400, 800 s mm(-2)) in 60 histologically proven SSTMs (35 benign and 25 malignant) excluding lipomas. Two radiologists independently evaluated the conventional MRI alone and again with the additional DWI for the evaluation of malignant masses. The mean ADC values measured within an entire mass and the contrast-enhancing solid portion were used for quantitative analysis. Diagnostic performances were compared using receiver operating characteristic analysis. RESULTS: For an inexperienced reader, using only conventional MRI, the sensitivity, specificity and accuracy were 84%, 80% and 81.6%, respectively. When combining conventional MRI and DWI, the sensitivity, specificity and accuracy were 96%, 85.7% and 90%, respectively. Additional DWI influenced the improvement of the rate of correct diagnosis by 8.3% (5/60). For an experienced reader, additional DWI revealed the same accuracy of 86.7% without added value on the correct diagnosis. The group mean ADCs of malignant SSTMs were significantly lower than that of benign SSTMs (p < 0.001). The best diagnostic performance with respect to differentiation of SSTMs could be obtained when conventional MRI was assessed in combination with DWI. CONCLUSION: Adding qualitative and quantitative DWI to conventional MRI can improve the diagnostic performance for the differentiation between benign and malignant SSTMs. ADVANCES IN KNOWLEDGE: Because the imaging characteristics of many malignant superficial soft-tissue lesions overlap with those of benign ones, inadequate surgical resection due to misinterpretation of MRI often occurs. Adding DWI to conventional MRI yields greater diagnostic performances [area under the receiver-operating characteristic curve (AUC), 0.83-0.99] than does the use of conventional MRI alone (AUC, 0.71-0.93) in the evaluation of malignant superficial masses by inexperienced readers. PMID- 26892268 TI - A room temperature approach for the fabrication of aligned TiO2 nanotube arrays on transparent conductive substrates. AB - A novel solution approach is reported for the fabrication of TiO2 nanotube arrays on transparent conductive substrates via in situ conversion from nanowires. The as-prepared nanotube arrays not only demonstrate a larger surface area in comparison with the primary NWs, but also longer charge carrier lifetime than that of randomly packed nanoparticle films. PMID- 26892270 TI - High-resolution ultrasound biomicroscopy as an adjunctive diagnostic tool for anterior scleral inflammatory disease. AB - PURPOSE: To study high-resolution ultrasound biomicroscopy (UBM) findings in anterior scleral inflammatory disease and evaluate the efficacy of high resolution UBM as an adjunctive diagnostic tool. METHODS: A cross-sectional study. The medical records of 30 patients (33 eyes) with episcleritis or anterior scleritis were reviewed for clinical features and high-resolution UBM findings. Ultrasound biomicroscopy (UBM) examination was performed using 50 MHz Aviso S (Quantel Medical, Clermont-Ferrand, France). RESULTS: Seventeen eyes had episcleritis [nodular (12), simple (five)], and 16 eyes had anterior scleritis [nodular (14), diffuse (two)] as classified by UBM. The use of high-resolution UBM allowed high-resolution imaging of the sclera and episclera and showed characteristic patterns of episcleritis and anterior scleritis. The clinical classification matched UBM findings in 25 (76%) eyes. In the other eight eyes (24%), UBM analysis led to a change in the final classification: four eyes with suspected episcleritis were classified with scleritis, and four eyes with suspected scleritis were classified with episcleritis. Eleven patients (36.7%) had an associated systemic disease. CONCLUSION: High-resolution UBM enabled visualization of distinct imaging findings of episcleritis and anterior scleritis, indicating its usefulness in the classification of challenging cases of anterior scleral inflammatory disease. PMID- 26892269 TI - Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner. AB - Physical forces arising in the extra-cellular environment have a profound impact on cell fate and gene regulation; however the underlying biophysical mechanisms that control this sensitivity remain elusive. It is hypothesized that gene expression may be influenced by the physical deformation of the nucleus in response to force. Here, using 3T3s as a model, we demonstrate that extra cellular forces cause cell nuclei to rapidly deform (<1 s) preferentially along their shorter nuclear axis, in an anisotropic manner. Nuclear anisotropy is shown to be regulated by the cytoskeleton within intact cells, with actin and microtubules resistant to orthonormal strains. Importantly, nuclear anisotropy is intrinsic, and observed in isolated nuclei. The sensitivity of this behaviour is influenced by chromatin organization and lamin-A expression. An anisotropic response to force was also highly conserved amongst an array of examined nuclei from differentiated and undifferentiated cell types. Although the functional purpose of this conserved material property remains elusive, it may provide a mechanism through which mechanical cues in the microenvironment are rapidly transmitted to the genome. PMID- 26892267 TI - The Role of Maternal-Effect Genes in Mammalian Development: Are Mammalian Embryos Really an Exception? AB - The essential contribution of multiple maternal factors to early mammalian development is rapidly altering the view that mammals have a unique pattern of development compared to other species. Currently, over 60 maternal-effect mutations have been described in mammalian systems, including critical determinants of pluripotency. This data, combined with the evidence for lineage bias and differential gene expression in early blastomeres, strongly suggests that mammalian development is to some extent mosaic from the four-cell stage onward. PMID- 26892272 TI - Lupeol enhances inhibitory effect of 5-fluorouracil on human gastric carcinoma cells. AB - Lupeol, a dietary triterpene present in many fruits and medicinal plants, has been reported to possess many pharmacological properties including cancer preventive and anti-cancer effects in vitro and in vivo. Here, we investigated the anti-cancer efficacy and adjuvant chemotherapy action of lupeol in gastric cancer (GC) cells (SGC7901 and BGC823) and explored the underlying mechanisms. Cells were treated with lupeol and/or 5-fluorouracil (5-Fu) and subjected to cell viability, colony formation, apoptosis, western blot, semiquantitative RT-PCR, and xenograft tumorigenicity assay. Our results showed that lupeol and 5-Fu inhibited the proliferation of SGC7901 and BGC823 cells, and combination treatment with lupeol and 5-Fu resulted in a combination index < 1, indicating a synergistic effect. Co-treatment with lupeol and 5-Fu induced apoptosis through up-regulating the expressions of Bax and p53 and down-regulating the expressions of survivin and Bcl-2. Furthermore, co-treatment displayed more efficient inhibition of tumor weight and volume on BGC823 xenograft mouse model than single agent treatment with 5-Fu or lupeol. Taken together, our findings highlight that lupeol sensitizes GC to 5-Fu treatment, and combination treatment with lupeol and 5-Fu would be a promising therapeutic strategy for human GC treatment. PMID- 26892271 TI - Inhibitory effect of a histamine 4 receptor antagonist on CCL17 and CCL22 production by monocyte-derived Langerhans cells in patients with atopic dermatitis. AB - We examined the inhibitory effect of a histamine 4 receptor (H4R) antagonist (JNJ7777120) on CCL17 and CCL22 chemokine production by human monocyte-derived Langerhans cells (MoLC) in patients with atopic dermatitis (AD) and healthy controls (HC). We confirmed the significantly higher production of both CCL17 and CCL22 in the MoLC of AD patients compared with HC. The H4R antagonist significantly inhibited the production of both CCL17 and CCL22 in the MoLC of AD patients. With regard to TLR2-signaled enhancement, peptidoglycan (PGN)-enhanced production of CCL17 and CCL22 by MoLC was inhibited by the H4R. Immunoblotting analysis demonstrated that phosphorylated p38 mitogen-activated protein kinase was induced by PGN and that this enhancement was attenuated by the application of the H4R antagonist. These data indicate that H4 signaling modulates the production of T-helper 2 chemokine in MoLC and contributes to chronic inflammation in AD patients. Our data suggest a possible novel therapeutic approach using a H4R antagonist in the treatment of patients with AD. PMID- 26892274 TI - Continuous endpoints in Bayesian two-stage designs. AB - Single-arm two-stage designs for phase II of clinical trials typically focus on a binary endpoint obtained by dichotomizing an underlying continuous measure of treatment efficacy. To avoid the resulting loss of information, we propose a two stage design based on a Bayesian predictive approach that directly uses the original continuous endpoint. Numerical results are provided with reference to phase II cancer trials aimed at assessing tumor shrinking effect of an experimental treatment. PMID- 26892273 TI - Amplified RLR signaling activation through an interferon-stimulated gene endoplasmic reticulum stress-mitochondrial calcium uniporter protein loop. AB - Type I interferon (IFN-I) is critical for a host against viral and bacterial infections via induction of hundreds of interferon-stimulated genes (ISGs), but the mechanism underlying the regulation of IFN-I remains largely unknown. In this study, we first demonstrate that ISG expression is required for optimal IFN-beta levels, an effect that is further enhanced by endoplasmic reticulum (ER) stress. Furthermore, we identify mitochondrial calcium uniporter protein (MCU) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein that is important for ER stress induction and amplified MAVS signaling activation. In addition, by performing an ectopic expression assay to screen a library of 117 human ISGs for effects on IFN-beta levels, we found that tumor necrosis factor receptor 1 (TNFR1) significantly increases IFN-beta levels independent of ER stress. Altogether, our findings suggest that MCU and TNFR1 are involved in the regulation of RIG-I-like receptors (RLR) signaling. PMID- 26892275 TI - Exercise, but not antioxidants, reversed ApoE4-associated motor impairments in adult GFAP-ApoE mice. AB - Motor dysfunction has been found to be predictive of cognitive dysfunction in Alzheimer's disease and to occur earlier than cognitive impairments. While apolipoprotein (Apo) E4 has been associated with cognitive impairments, it remains unclear whether it also increases risk for motor dysfunction. Exercise and antioxidants are often recommended to reduce cognitive declines, however it is unclear whether they can successfully improve motor impairments. This study was designed to determine the extent of the impact of apolipoprotein genotype on motor function, and whether interventions such as exercise and antioxidant intake can improve motor function. This study is the first to identify the nature of the interaction between antioxidant intake and exercise using a mouse model expressing either the human ApoE3 or ApoE4 isoforms under glial fibrillary acid protein promoter (GFAP-ApoE3 and GFAP-ApoE4 mice). The mice were fed either a control diet or the control diet supplemented with vitamins E and C (1.12 IU/g diet alpha-tocopheryl acetate and 1.65mg/g ascorbic acid). Each genotype/diet group was further divided into a sedentary group or a group that followed a 6 days a week exercise regimen. After 8 weeks on their respective treatment, the mice were administered a battery of motor tests to measure reflexes, strength, coordination and balance. GFAP-ApoE4 mice exhibited impaired motor learning and diminished strength compared to the GFAP-ApoE3 mice. Exercise alone was more efficient at improving motor function and reversing ApoE4-associated impairments than antioxidants alone, even though improvements were rather subtle. Contrarily to expected outcomes, combination of antioxidants and exercise did not yield further improvements of motor function. Interestingly, antioxidants antagonized the beneficial effects of exercise on strength. These data suggest that environmental and genetic factors influence the outcome of interventions on motor function and should be investigated more thoroughly and taken into consideration when implementing changes in lifestyles. PMID- 26892277 TI - 3D Oxidized Graphene Frameworks for Efficient Nano Sieving. AB - The small size of Na(+) and Cl(-) ions provides a bottleneck in desalination and is a challenge in providing alternatives for continuously depleting fresh water resources. Graphene by virtue of its structural properties has the potential to address this issue. Studies have indicated that use of monolayer graphene can be used to filter micro volumes of saline solution. Unfortunately it is extremely difficult, resource intensive and almost impractical with current technology to fabricate operational devices using mono-layered graphene. Nevertheless, graphene based devices still hold the key to solve this problem due to its nano-sieving ability. Here we report synthesis of oxidized graphene frameworks and demonstrate a functional device to desalinate and purify seawater from contaminants including Na(+) and Cl(-) ions, dyes and other microbial pollutants. Micro-channels in these frameworks help in immobilizing larger suspended solids including bacteria, while nano-sieving through graphene enables the removal of dissolved ions (e.g. Cl(-)). Nano-sieving incorporated with larger frameworks has been used in filtering Na(+) and Cl(-) ions in functional devices. PMID- 26892276 TI - High-dose cutaneous exposure to mite allergen induces IgG-mediated protection against anaphylaxis. AB - BACKGROUND: The relationship among natural allergen exposure, induction of blocking antibody and the occurrence of atopic allergy-particularly in the presence of IgE production-is debatable. OBJECTIVE: To clarify the relationship between the dose of cutaneous exposure to dust mite allergen and susceptibility to the IgE-mediated allergic response in relation to IgG production. METHODS: NC/Nga mice were epicutaneously exposed to various doses of Dermatophagoides pteronyssinus allergen to induce atopic dermatitis-like skin lesions. We then evaluated the skin lesions, induction of mite-specific immune responses, and susceptibility to anaphylaxis. RESULTS: Dose-dependent exacerbation of atopic dermatitis-like skin lesions and increases in mite-specific IgG and IgE production were observed. However, mice exposed to relatively low doses of mite allergen showed hypersusceptibility to mite allergen-specific anaphylaxis. We also showed that adoptive transfer of total IgG from Dp-sensitized mice rescued mice from the hypersusceptibility seen in those exposed to low doses of mite allergen. CONCLUSIONS AND CLINICAL RELEVANCE: High-dose cutaneous exposure to dust mites induced effective blocking IgG production, even if accompanied by IgE production. Our data might support the concept that an increase in IgG titre, not a decrease in IgE titre, is a marker of clinical improvement in allergen-specific immunotherapy. PMID- 26892278 TI - Vascularized jejunal mesenteric lymph node transfer for treatment of extremity lymphedema. PMID- 26892279 TI - Assessment of Home-Time After Acute Ischemic Stroke in Medicare Beneficiaries. AB - BACKGROUND AND PURPOSE: Stroke survivors have identified home-time as a meaningful outcome. We evaluated home-time as a patient-centered outcome in Medicare beneficiaries with ischemic stroke in comparison with modified Rankin Scale (mRS) score at 90 days and at 1 year post event. METHODS: Patients enrolled in Get With The Guidelines-Stroke (GWTG-Stroke) and Adherence Evaluation After Ischemic Stroke-Longitudinal (AVAIL) registries were linked to Medicare claims to ascertain home-time, defined as time spent alive and out of a hospital, inpatient rehabilitation, or skilled nursing facilities, at 90 days and at 1 year after admission. The correlation of home-time with mRS at 90 days and at 1 year was evaluated by Pearson correlation coefficients, and the ability of home-time to discriminate mRS (0-2) was assessed by c-index. RESULTS: There were 815 patients with ischemic stroke (age median, 76 years [interquartile range {IQR}, 70-82]; 46% women; National Institutes of Health Stroke Scale median, 4 [IQR, 2-7]) from 88 hospitals. The 90-day and 1-year median home-times were 79 (IQR, 52-86) days and 349 (IQR, 303-360) days and median mRS were 2 (IQR, 1-4) and 2 (IQR, 1-4). Greater home-time within 90 days was significantly correlated with lower 90-day mRS (Pearson correlation coefficient, -0.731; P<0.0001) and showed strong ability to discriminate functional independence with mRS 0 to 2 (c-index, 0.837). Similar findings were observed at 1 year. CONCLUSIONS: In a population of older patients with ischemic stroke, home-time was readily available from administrative data and associated with mRS at 90 days and 1 year. Home-time represents a novel, easily measured, patient-centered, outcome measure for an episode of stroke care. PMID- 26892280 TI - Stroke in Commercial Flights. AB - BACKGROUND AND PURPOSE: Stroke on board aircraft has been reported in retrospective case series, mainly focusing on economy class stroke syndrome. Data on the actual incidence, pathogenesis, and prognosis of stroke in commercial flights are lacking. METHODS: A prospective registry was designed to include all consecutive patients referred from an international airport (40 million passengers a year) to our hospital with a diagnosis of ischemic stroke or transient ischemic attack and onset of symptoms during a flight or immediately after landing. RESULTS: Forty-four patients (32 ischemic strokes and 12 transient ischemic attacks) were included over a 76-month period (January 2008 to April 2014). The estimated incidence of stroke was 1 stroke in 35 000 flights. Pathogeneses of stroke or transient ischemic attack were atherothrombotic in 16 (36%), economy class stroke syndrome in 8 (18%), cardioembolic in 7 (16%), arterial dissection in 4 (9%), lacunar stroke in 4 (9%), and undetermined in 5 (12%) patients. Carotid stenosis >70% was found in 12 (27%) of the patients. Overall prognosis was good, and thrombolysis was applied in 44% of the cases. The most common reason for not treating patients who had experienced stroke onset midflight was the delay in reaching the hospital. Only 1 patient with symptom onset during the flight prompted a flight diversion. CONCLUSIONS: We found a low incidence of stroke in the setting of air travel. Economy class stroke syndrome and arterial dissection were well represented in our sample. However, the main pathogenesis was atherothrombosis with a high proportion of patients with high carotid stenosis. PMID- 26892282 TI - Streamlined Hyperacute Magnetic Resonance Imaging Protocol Identifies Tissue-Type Plasminogen Activator-Eligible Stroke Patients When Clinical Impression Is Stroke Mimic. AB - BACKGROUND AND PURPOSE: Stroke mimics (SM) challenge the initial assessment of patients presenting with possible acute ischemic stroke (AIS). When SM is considered likely, intravenous tissue-type plasminogen activator (tPA) may be withheld, risking an opportunity to treat AIS. Although computed tomography is routinely used for tPA decision making, magnetic resonance imaging (MRI) may diagnose AIS when SM is favored but not certain. We hypothesized that a hyperacute MRI (hMRI) protocol would identify tPA-eligible AIS patients among those initially favored to have SM. METHODS: A streamlined hMRI protocol was designed based on barriers to rapid patient transport, MRI acquisition, and post MRI tPA delivery. Neurologists were trained to order hMRI when SM was favored and tPA was being withheld. The use of hMRI for tPA decision making, door-to-needle times, and outcomes were compared before hMRI implementation (pre-hMRI: August 1, 2011 to July 31, 2013) and after (post-hMRI, August 1, 2013, to January 15, 2015). RESULTS: Post hMRI, 57 patients with suspected SM underwent hMRI (median MRI-order-to-start time, 29 minutes), of whom, 11 (19%) were diagnosed with AIS and 7 (12%) received tPA. Pre-hMRI, no tPA-treated patients were screened with hMRI. Post hMRI, 7 of 106 (6.6%) tPA-treated patients underwent hMRI to aid in decision making because of suspected SM (0% versus 6.6%; P=0.001). To ensure standard care was maintained after implementing the hMRI protocol, pre- versus post-hMRI tPA-treated cohorts were compared and did not differ: door-to-needle time (39 versus 37 minutes; P=0.63), symptomatic hemorrhage rate (4.5% versus 1.9%; P=0.32), and favorable discharge location (85% versus 89%; P=0.37). CONCLUSIONS: A streamlined hMRI protocol permitted tPA administration to a small, but significant, subset of AIS patients initially considered to have SM. PMID- 26892281 TI - Racial and Socioeconomic Disparities in Gastrostomy Tube Placement After Intracerebral Hemorrhage in the United States. AB - BACKGROUND AND PURPOSE: Percutaneous endoscopic gastrostomy (PEG) tubes are widely used for enteral feeding of patients after intracerebral hemorrhage (ICH). We sought to determine whether PEG placement after ICH differs by race and socioeconomic status. METHODS: Patient discharges with ICH as the primary diagnosis from 2007 to 2011 were queried from the Nationwide Inpatient Sample. Logistic regression was used to evaluate the association between race, insurance status, and household income with PEG placement. RESULTS: Of 49 946 included ICH admissions, a PEG was placed in 4464 (8.94%). Among PEG recipients, 47.2% were minorities and 15.6% were Medicaid enrollees, whereas 33.7% and 8.2% of patients without a PEG were of a race other than white and enrolled in Medicaid, respectively (P<0.001). Compared with whites, the odds of PEG were highest among Asians/Pacific Islanders (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.32 1.99) and blacks (OR 1.42, 95% CI 1.28-1.59). Low household income (OR 1.25, 95% CI 1.09-1.44 in lowest compared with highest quartile) and enrollment in Medicaid (OR 1.36, 95% CI 1.17-1.59 compared with private insurance) were associated with PEG placement. Racial disparities (minorities versus whites) were most pronounced in small/medium-sized hospitals (OR 1.77, 95% CI 1.43-2.20 versus OR 1.31, 95% CI 1.17-1.47 in large hospitals; P value for interaction 0.011) and in hospitals with low ICH case volume (OR 1.58, 95% CI 1.38-1.81 versus OR 1.29, 95% CI 1.12 1.50 in hospitals with high ICH case volume; P value for interaction 0.007). CONCLUSIONS: Minority race, Medicaid enrollment, and low household income are associated with PEG placement after ICH. PMID- 26892285 TI - Population inference from contemporary American craniometrics. AB - OBJECTIVES: This analysis delivers a composite picture of population structure, admixture, ancestry variation, and personal identity in the United States, as observed through the lens of forensic anthropological casework and modern skeletal collections. It tests the applicability of the probabilistic clustering methods commonly used in human population genetics for the analysis of continuous, cranial measurement data, to improve population inference for admixed individuals without prior knowledge of sample origins. MATERIALS AND METHODS: The unsupervised model-based clustering methods of finite mixture analysis are used here to reveal latent population structure and generate admixture proportions for craniofacial measurements from the Forensic Anthropology Data Bank (FDB). Craniometric estimates of ancestry are also generated under a three contributor model, sourcing parental reference populations from the Howells Craniometric Dataset. Tests of association are made among the coefficients of cluster memberships and the demographic information documented for each individual in the FDB. Clustering results are contextualized within the framework of conventional approaches to population structure analysis and individual ancestry estimation to discuss method compatibility. RESULTS: The findings reported here for contemporary American craniometrics are in agreement with the expected patterns of intergroup relationships, geographic origins and results from published genetic analyses. DISCUSSION: Population inference methods that allow for the model-bound estimation of admixture and ancestry proportions from craniometric data not only enable parallel-skeletal and genetic-analyses but they are also shown to be more informative than those methods that perform hard classifications using externally-imposed categories or seek to explain gross variation by low dimensional projections. Am J Phys Anthropol 160:604-624, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26892283 TI - Magnitude of Hematoma Volume Measurement Error in Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: Limiting intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) expansion is a common target for acute ICH studies and, therefore, accurate measurement of hematoma volumes is required. We investigated the amount of hematoma volume difference between computed tomography scans that can be considered as measurement error. METHODS: Five raters performed baseline (<6 hours) and 24-hour total hematoma (ICH+IVH) computer-assisted volumetric analysis from 40 selected ICH patients from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study cohort twice. Estimates of intrarater and interrater reliability are expressed as intraclass correlation coefficients and minimum detectable difference (MDD). RESULTS: Total hematoma volumetric analyses had excellent intra and interrater agreements (intraclass correlation coefficients 0.994 and 0.992, respectively). MDD for intra- and interrater volumes was 6.68 and 7.72 mL, respectively, and were higher the larger total hematoma volume was and in patients with subarachnoid hemorrhage or IVH. MDD for total hematoma volume measurement of 10.4 mL was found in patients with largest hematoma volumes. In patients with subarachnoid hemorrhage or IVH, MDD for total hematoma volume was 10.3 and 10.4 mL, respectively. In patients without IVH, MDD for intra- and interrater pure ICH volumes were 3.82 and 5.83 mL, respectively. CONCLUSIONS: A threshold higher than 10.4 mL seems to be reliable to avoid error of total hematoma volume measurement in a broad range of patients. An absolute ICH volume increase of >6 mL, commonly used as outcome in ICH studies, seems well above MDD and, therefore, could be used to reliably detect ICH expansion. PMID- 26892286 TI - A Rare Cause of Bilateral Conductive Hearing Loss in a Young Boy. PMID- 26892284 TI - Intra-Arterial Therapy and Post-Treatment Infarct Volumes: Insights From the ESCAPE Randomized Controlled Trial. AB - BACKGROUND AND PURPOSE: The goal of reperfusion therapy in acute ischemic stroke is to limit brain infarction. The objective of this study was to investigate whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in post-treatment infarct volume. METHODS: The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 315 enrolled subjects (endovascular treatment n=165; control n=150), 314 subject's infarct volumes at 24 to 48 hours on magnetic resonance imaging (n=254) or computed tomography (n=60) were measured. Post-treatment infarct volumes were compared by treatment assignment and recanalization/reperfusion status. Appropriate statistical models were used to assess relationship between baseline clinical and imaging variables, post-treatment infarct volume, and functional status at 90 days (modified Rankin Scale). RESULTS: Median post-treatment infarct volume in all subjects was 21 mL (interquartile range =65 mL), in the intervention arm, 15.5 mL (interquartile range =41.5 mL), and in the control arm, 33.5 mL (interquartile range =84 mL; P<0.01). Baseline National Institute of Health Stroke Scale (P<0.01), site of occlusion (P<0.01), baseline noncontrast computed tomographic scan Alberta Stroke Program Early CT score (ASPECTS) (P<0.01), and recanalization (P<0.01) were independently associated with post treatment infarct volume, whereas age, sex, treatment type, intravenous alteplase, and time from onset to randomization were not (P>0.05). Post-treatment infarct volume (P<0.01) and delta National Institute of Health Stroke Scale (P<0.01) were independently associated with 90-day modified Rankin Scale, whereas laterality (left versus right) was not. CONCLUSIONS: These results support the primary results of the ESCAPE trial and show that the biological underpinning of the success of endovascular therapy is a reduction in infarct volume. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335. PMID- 26892287 TI - The Putative Use of Lithium in Alzheimer's Disease. AB - Alzheimer's disease is a progressive neurodegenerative illness characterized by the invariant existence of beta-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Abeta cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using "microdose" lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit. PMID- 26892288 TI - Population Studies of Association Between Lithium and Risk of Neurodegenerative Disorders. AB - BACKGROUND: Lithium shows neuroprotective and neurotrophic effects in vitro and in vivo. Due to its involvement in hippocampal neurogenesis and the interaction with beta-amyloid and neurofibrillary tangle metabolism it has been hypothesized that lithium could have the potential to influence the development of dementia. METHOD: Using the PubMed database and cross-reference search strategies our aim was to specifically identify population (cohort or case-control) studies investigating the association between lithium and dementia. RESULTS: Data from large cohort studies suggest an association between lithium treatment and dementia risk reduction or reduced dementia severity. Studies with smaller sample sizes yield more variable findings. CONCLUSIONS: Lithium may reduce the risk of dementia among middle-aged and older people. Beneficial lithium effects are possibly limited to specific types of neurodegenerative processes. PMID- 26892289 TI - Lithium, a Therapy for AD: Current Evidence from Clinical Trials of Neurodegenerative Disorders. AB - BACKGROUND: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer's disease (AD), Huntigton's disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. METHODS: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014. RESULTS: Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (aMCI, 1 study) and AD (2 studies), even with doses lower than those used for mood stabilisation. Studies of Li in HD, MSA and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease. CONCLUSION: In absence of disease modifying treatments for any neurodegenerative disorders, the fact that at least 3 studies supported the effect of lithium in aMCI/AD is noteworthy. Future studies should focus on defining the dose range necessary for neuroprotective effects to occur. PMID- 26892290 TI - Neuroprotective Effects of Lithium in Human Brain? Food for Thought. AB - BACKGROUND: There is a growing body of pre-clinical evidence suggesting that lithium (Li) may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects? METHODS: We reviewed the neuroimaging literature investigating the association between Li treatment and brain structure. RESULTS: There is level I evidence for positive association between Li treatment and brain grey matter volume, which is one of the most replicated neuroimaging findings. It has been reported in the majority of cross sectional studies, all 8 prospective studies, including a randomized controlled trial as well as in 2 meta-analyses and one mega-analysis. The association between Li treatment and grey matter volume occurs regardless of mood state, diagnostic subtype, presence or absence of concomitant medications. It was documented in multiple brain regions, including hippocampus, amygdala, anterior cingulate, subgenual cingulate, inferior frontal gyrus, postcentral gyrus, habenula. CONCLUSION: Although some methodological and clinical issues complicate the interpretation of findings, there is robust and highly replicated level 1 evidence for positive association between Li treatment and grey matter volumes. These "neuroprotective" effects of Li have been shown even in healthy subjects and appear independent of prophylactic treatment response. Consequently, Li might help maintain brain health even in patients without bipolar disorders and could possibly demonstrate diseasemodifying properties in neurodegenerative disorders. PMID- 26892291 TI - Lithium Distinctly Modulates the Secretion of Pro- and Anti- Inflammatory Interleukins in Co-Cultures of Neurons and Glial Cells at Therapeutic and Sub Therapeutic Concentrations. AB - Lithium is associated with various effects on immune functions, some of which are still poorly understood. The roles of many cytokines have been characterized in a variety of neurodevelopmental processes including neurogenesis, neuronal and glial cell migration, proliferation, differentiation, synaptic maturation and synaptic pruning. This work aims to evaluate the effects of different doses of lithium (0.02; 0.2 and 2mM) on the secretion of cytokines in co-cultures of cortical and hippocampal neurons with glial cells. Our results indicate that chronic treatment with lithium chloride at subtherapeutic concentrations are able to modify the secretion of pro- and anti-inflammatory interleukins in co-cultures of cortical and hippocampal neurons with glial cells. PMID- 26892292 TI - Describing a complex and changing landscape: metrics for understanding and planning chlamydia control. PMID- 26892293 TI - Effects of developmental hyperserotonemia on the morphology of rat dentate nuclear neurons. AB - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social cognition, disordered communication, restricted interests and repetitive behaviors. Furthermore, abnormalities in basic motor control, skilled motor gestures, and motor learning, are common in ASD. These characteristics have been attributed to a possible defect in the pre- and postnatal development of specific neural networks including the dentate-thalamo-cortical pathway, which is involved in motor learning, automaticity of movements, and higher cognitive functions. The current study utilized custom diolistic labeling and unbiased stereology to characterize morphological alterations in neurons of the dentate nucleus of the cerebellum in developing rat pups exposed to abnormally high levels of the serotonergic agonist 5-methyloxytryptamine (5-MT) pre-and postnatally. Occurring in as many as 30% of autistic subjects, developmental hyperserotonemia (DHS) is the most consistent neurochemical finding reported in autism and has been implicated in the pathophysiology of ASD. This exposure produced dramatic changes in dendritic architecture and synaptic features. We observed changes in the dendritic branching morphology which did not lead to significant differences (p>0.5) in total dendritic length. Instead, DHS groups presented with dendritic trees that display changes in arborescence, that appear to be short reaching with elaborately branched segments, presenting with significantly fewer (p>0.001) dendritic spines and a decrease in numeric density when compared to age-matched controls. These negative changes may be implicated in the neuropathological and functional/behavioral changes observed in ASD, such as delays in motor learning, difficulties in automaticity of movements, and deficits in higher cognitive functions. PMID- 26892296 TI - Effect of circadian rhythm disturbance on morphine preference and addiction in male rats: Involvement of period genes and dopamine D1 receptor. AB - It is claimed that a correlation exists between disturbance of circadian rhythms by factors such as alteration of normal light-dark cycle and the development of addiction. However, the exact mechanisms involved in this relationship are not much understood. Here we have studied the effect of constant light on morphine voluntary consumption and withdrawal symptoms and also investigated the involvement of Per1, Per2 and dopamine D1 receptor in these processes. Male wistar rats were kept under standard (LD) or constant light (LL) conditions for one month. The plasma concentration of melatonin was evaluated by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was used to determine the mRNA expression of Per1, Per2 and dopamine D1 receptor in the striatum and prefrontal cortex. Morphine preference (50mg/L) was evaluated in a two-bottle-choice paradigm for 10 weeks and withdrawal symptoms were recorded after administration of naloxone (3mg/kg). One month exposure to constant light resulted in a significant decrease of melatonin concentration in the LL group. In addition, mRNA levels of Per2 and dopamine D1 receptor were up-regulated in both the striatum and prefrontal cortex of the LL group. However, expression of Per1 gene was only up-regulated in the striatum of LL rats in comparison to LD animals. Furthermore, after one month exposure to constant light, morphine consumption and preference ratio and also severity of naloxone-induced withdrawal syndrome were significantly greater in LL animals. It is concluded that exposure to constant light by up-regulation of Per2 and dopamine D1 receptor in the striatum and prefrontal cortex and up-regulation of Per1 in the striatum and the possible involvement of melatonin makes animals vulnerable to morphine preference and addiction. PMID- 26892294 TI - Toward understanding the impact of trauma on the early developing human brain. AB - Traumatic experiences early in life predispose animals and humans to later cognitive-behavioral, emotional, and somatic problems. In humans, traumatic experiences are strong predictors of psychiatric illness. A growing body of research has emphasized alterations in neurological structure and function that underscore phenotypic changes following trauma. However, results are mixed and imprecise. We argue that future translation of neurological findings to clinical practice will require: (1) discovery of neurobehavioral associations within a longitudinal context, (2) dissociation of trauma types and of trauma versus chronic stress, and (3) better localization of neural sequelae considerate of the fine resolution of neural circuitry. We provide a brief overview of early brain development and highlight the role of longitudinal research in unearthing brain behavior relations in youth. We relay an emergent framework in which dissociable trauma types are hypothesized to impact distinct, rationally informed neural systems. In line with this, we discuss the long-standing challenge of separating effects of chronic stress and trauma, as these are often intertwined. We bring to light inconsistencies in localization of neural correlates of trauma, emphasizing results in medial prefrontal regions. We assert that more precise spatial brain localization will help to advance prevailing models of trauma pathways and inform future research. PMID- 26892295 TI - Developmental ethanol exposure-induced sleep fragmentation predicts adult cognitive impairment. AB - Developmental ethanol (EtOH) exposure can lead to long-lasting cognitive impairment, hyperactivity, and emotional dysregulation among other problems. In healthy adults, sleep plays an important role in each of these behavioral manifestations. Here we explored circadian rhythms (activity, temperature) and slow-wave sleep (SWS) in adult mice that had received a single day of EtOH exposure on postnatal day 7 and saline littermate controls. We tested for correlations between slow-wave activity and both contextual fear conditioning and hyperactivity. Developmental EtOH resulted in adult hyperactivity within the home cage compared to controls but did not significantly modify circadian cycles in activity or temperature. It also resulted in reduced and fragmented SWS, including reduced slow-wave bout duration and increased slow-wave/fast-wave transitions over 24-h periods. In the same animals, developmental EtOH exposure also resulted in impaired contextual fear conditioning memory. The impairment in memory was significantly correlated with SWS fragmentation. Furthermore, EtOH treated animals did not display a post-training modification in SWS which occurred in controls. In contrast to the memory impairment, sleep fragmentation was not correlated with the developmental EtOH-induced hyperactivity. Together these results suggest that disruption of SWS and its plasticity are a secondary contributor to a subset of developmental EtOH exposure's long-lasting consequences. PMID- 26892297 TI - Postnatal development of GABAergic interneurons in the neocortical subplate of mice. AB - The subplate (SP) plays important roles in developmental and functional events in the neocortex, such as thalamocortical and corticofugal projection, cortical oscillation generation and corticocortical connectivity. Although accumulated evidence indicates that SP interneurons are crucial for SP function, the molecular composition of SP interneurons as well as their developmental profile and distribution remain largely unclear. In this study, we systematically investigated dynamic development of SP thickness and chemical marker expression in SP interneurons in distinct cortical regions during the first postnatal month. We found that, although the relative area of the SP in the cerebral cortex significantly declined with postnatal development, the absolute thickness did not change markedly. We also found that somatostatin (SOM), the ionotropic serotonin receptor 3A (5HT3AR), and parvalbumin (PV) reliably identify three distinct non overlapping subpopulations of SP interneurons. The SOM group, which represents ~30% of total SP interneurons, expresses neuronal nitric oxide synthase (nNOS) and calbindin (CB) and colocalizes entirely with neuropeptide Y (NPY). The 5HT3AR group, which accounts for ~60% of the total interneuronal population, expresses calretinin (CR) and GABA-A receptor subunit delta (GABAARdelta). The PV group accounts for ~10% of total SP interneurons and coexpressed GABAARdelta. Moreover, distinct interneuron subtypes show characteristic temporal and spatial distribution in the SP. nNOS(+) interneurons in the SP increase from the anterior motor cortex to posterior visual cortex, while CR(+) and CB(+) interneurons the opposite. Interestedly, the majority of GABAARdelta(+) neurons in SP are non GABAergic neurons in contrast to other cortical layers. These findings clarify and extend our understanding of SP interneurons in the developing cerebral cortex and will underpin further study of SP function. PMID- 26892299 TI - Neocortical slices from adult chronic epileptic rats exhibit discharges of higher voltages and broader spread. AB - Much of the current understanding of epilepsy mechanisms has been built on data recorded with one or a few electrodes from temporal lobe slices of normal young animals stimulated with convulsants. Mechanisms of adult, extratemporal, neocortical chronic epilepsy have not been characterized as much. A more advanced understanding of epilepsy mechanisms can be obtained by recording epileptiform discharges simultaneously from multiple points of an epileptic focus so as to define their sites of initiation and pathways of spreading. Brain slice recordings can characterize epileptic mechanisms in a simpler, more controlled preparation than in vivo. Yet, the intrinsic hyper-excitability of a chronic epileptic focus may not be entirely preserved in slices following the severing of connections in slice preparation. This study utilizes recordings of multiple electrode arrays to characterize which features of epileptic hyper-excitability present in in vivo chronic adult neocortical epileptic foci are preserved in brain slices. After tetanus toxin somatosensory cortex injections, adult rats manifest chronic spontaneous epileptic discharges both in the injection site (primary focus) and in the contralateral side (secondary focus). We prepared neocortical slices from these epileptic animals. When perfused with 4 Aminopyridine in a magnesium free medium, epileptic rat slices exhibit higher voltage discharges and broader spreading than control rat slices. Rates of discharges are similar in slices of epileptic and normal rats, however. Ictal and interictal discharges are distributed over most cortical layers, though with significant differences between primary and secondary foci. A chronic neocortical epileptic focus in slices does not show increased spontaneous pacemakers initiating epileptic discharges but shows discharges with higher voltages and broader spread, consistent with an enhanced synchrony of cellular and synaptic generators over wider surfaces. PMID- 26892298 TI - Anodal transcranial direct current stimulation enhances time to task failure of a submaximal contraction of elbow flexors without changing corticospinal excitability. AB - BACKGROUND: The increase in corticospinal excitability in response to anodal transcranial direct current stimulation (a-tDCS) may contribute to decrease neuromuscular fatigability. OBJECTIVE: This study investigated the effects of a tDCS on neuromuscular fatigability in relation with changes in corticospinal excitability. METHODS: Eleven adults participated in two experimental sessions consisting of two submaximal voluntary contractions (35% maximal torque) performed to failure, one hour apart with the right elbow flexor muscles. Sham stimulation (90 s) and a-tDCS (10 min) were applied in two separate sessions 10 min prior to the second fatiguing contraction. Corticospinal excitability was assessed by recording motor-evoked potential (MEP), elicited by transcranial magnetic stimulation (TMS) of the motor cortex, in biceps brachii, brachioradialis and triceps brachii during the first (C1) and second (C2) fatiguing contractions. The silent period (SP) in electromyogramme (EMG) that followed MEP was also recorded for biceps brachii and brachioradialis. RESULTS: Time to failure was briefer for C2 than C1 in both experimental sessions, but the decrease was less pronounced after a-tDCS (-14.4+/-12.7%) than sham stimulation ( 23.3+/-11.9%; p=0.04). MEP amplitude (+9.7+/-4.0%) and SP duration (+22.5+/ 12.8%) in biceps brachii and brachioradialis increased significantly (p<0.05) during C1 and C2, but to a similar extent in both sessions (p>0.05). A similar result was observed for MEP amplitude in triceps brachii. No association was found between changes in time to task failure of C2 and corticospinal excitability. CONCLUSION: The reduced neuromuscular fatigability induced by a tDCS does not rely on changes in the excitability of the corticospinal pathway of both agonist and antagonist muscles. PMID- 26892300 TI - Treatment modalities for advanced ALK-rearranged non-small-cell lung cancer. AB - The ALK gene plays a key role in the pathogenesis of non-small-cell lung cancer (NSCLC). Patients with NSCLC harboring an ALK-rearrangement represent the second oncogene addiction to be identified in this disease. Crizotinib was the first ALK inhibitor showing pronounced clinical activity, and is now a reference treatment for ALK-positive NSCLC disease. However, despite initial impressive responses to crizotinib, acquired resistance almost invariably develops within 12 months. The pressing need for effective second-line agents has prompted the rapid development of next-generation ALK inhibitors. These agents, notably ceritinib and alectinib as the most developed, have a higher potency against ALK than crizotinib, along with activity against tumors harboring crizotinib-resistant mutations and potentially improved CNS penetration. PMID- 26892303 TI - The bereavement experience of spousal caregivers to persons with dementia: Reclaiming self. AB - Spouses of persons living with dementia both anticipate future loss and grieve for multiple losses occurring with caregiving and this ultimately influences their bereavement experience. Little research has been conducted regarding the bereavement experience in the caregiving journey with dementia and what does exist is mostly quantitative in nature. The purpose of this study is to describe the bereavement experience of spousal caregivers ( n = 10) utilizing Thorne's interpretive description. Thematic analysis revealed the features and facilitators of the bereavement process for spousal caregivers to persons with dementia. The unique contribution of this study to the dementia literature is the finding that the overall process of reclaiming self is significant to the bereavement journey. Future work should investigate identity as understood by spousal caregivers to persons with dementia, and further explore the processes, facilitators, and barriers to healthy bereavement in this population. PMID- 26892301 TI - Stereological assessment of sexual dimorphism in the rat liver reveals differences in hepatocytes and Kupffer cells but not hepatic stellate cells. AB - There is long-standing evidence that male and female rat livers differ in enzyme activity. More recently, differences in gene expression profiling have also been found to exist; however, it is still unclear whether there is morphological expression of male/female differences in the normal liver. Such differences could help to explain features seen at the pathological level, such as the greater regenerative potential generally attributed to the female liver. In this paper, hepatocytes (HEP), Kupffer cells (KC) and hepatic stellate cells (HSC) of male and female rats were examined to investigate hypothesised differences in number, volume and spatial co-localisation of these cell types. Immunohistochemistry and design-based stereology were used to estimate total numbers, numbers per gram and mean cell volumes. The position of HSC within lobules (periportal vs. centrilobular) and their spatial proximity to KC was also assessed. In addition, flow cytometry was used to investigate the liver ploidy. In the case of HEP and KC, differences in the measured cell parameters were observed between male and female specimens; however, no such differences were detected for HSC. Female samples contained a higher number of HEP per gram, with more binucleate cells. The HEP nuclei were smaller in females, which was coincident with more abundant diploid particles in these animals. The female liver also had a greater number of KC per gram, with a lower percentage of KC in the vicinity of HSC compared with males. In this study, we document hitherto unknown morphological sexual dimorphism in the rat liver, namely in HEP and KC. These differences may account for the higher regenerative potential of the female liver and lend weight to the argument for considering the rat liver as a sexually dimorphic organ. PMID- 26892302 TI - Elevated pulmonary artery pressure and brain natriuretic peptide in high altitude pulmonary edema susceptible non-mountaineers. AB - Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 +/- 3.63 vs 15.68 +/- 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 +/- 32.9 vs 15.05 +/- 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 +/- 5.8 vs 19.33 +/- 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID- 26892304 TI - Measuring positive attitudes toward persons with dementia: A validation of the Allophilia scale. AB - Efforts to combat ageism typically focus on negative attitudes toward members of an out-group. Changing attitudes also requires assessment and enhancement of positive attitudes. This study examined the psychometric properties of Allophilia scale when used to measure college students' positive attitudes toward persons with dementia. Data collected from 465 students were analyzed using confirmatory factor analysis and multigroup analysis by gender to assess the validity and reliability of the Allophilia scale. Results showed that the Allophilia scale is valid both for male and female students. The Allophilia scale is a valid assessment tool for measuring positive attitudes toward persons with dementia. Use of this scale will contribute to our understanding of attitudes toward persons with dementia and has implications for the design of interventions to facilitate positive attitudes toward members of this out-group. PMID- 26892306 TI - Editorial: Generation and cohort effects: Toward a better understanding of the nurse - elder relationship. PMID- 26892305 TI - Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease. AB - Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood-brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid beta (Abeta) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Abeta pathology clearly visualize Abeta in the brain. The PET signal increases with age and correlates closely with brain Abeta levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging. PMID- 26892307 TI - Changes in Olfactory Receptor Expression Are Correlated With Odor Exposure During Early Development in the zebrafish (Danio rerio). AB - We have previously shown that exposure to phenyl ethyl alcohol (PEA) causes an increase in the expression of the transcription factor otx2 in the olfactory epithelium (OE) of juvenile zebrafish, and this change is correlated with the formation of an odor memory of PEA. Here, we show that the changes in otx2 expression are specific to betaPEA: exposure to alphaPEA did not affect otx2 expression. We identified 34 olfactory receptors (ORs) representing 16 families on 4 different chromosomes as candidates for direct regulation of OR expression via Otx2. Subsequent in silico analysis uncovered Hnf3b binding sites closely associated with Otx2 binding sites in the regions flanking the ORs. Analysis by quantitative polymerase chain reaction and RNA-seq of OR expression in developing zebrafish exposed to different isoforms of PEA showed that a subset of ORs containing both Otx2/Hnf3b binding sites were downregulated only in betaPEA exposed juveniles and this change persisted through adult life. Localization of OR expression by in situ hybridization indicates the downregulation occurs at the level of RNA and not the number of cells expressing a given receptor. Finally, analysis of immediate early gene expression in the OE did not reveal changes in c fos expression in response to either alphaPEA or betaPEA. PMID- 26892308 TI - TongueSim: Development of an Automated Method for Rapid Assessment of Fungiform Papillae Density for Taste Research. AB - Taste buds are found on the tongue in 3 types of structures: the fungiform papillae, the foliate papillae, and the circumvallate papillae. Of these, the fungiform papillae (FP) are present in the greatest numbers on the tongue, and are thought to be correlated to the overall number of taste buds. For this reason, FP density on the tongue is often used to infer taste function, although this has been controversial. Historically, videomicroscopy techniques were used to assess FP. More recently, advances in digital still photography and in software have allowed the development of rapid methods for obtaining high quality images in situ. However, these can be subject to inter-researcher variation in FP identification, and are somewhat limited in the parameters that can be measured. Here, we describe the development of a novel, automated method to count the FP, using the TongueSim suite of software. Advantages include the reduction in time required for image analysis, elimination of researcher bias, and the added potential to measure characteristics such as the degree of roundness of each papilla. We envisage that such software has a wide variety of novel research applications. PMID- 26892309 TI - Behavioral Responses of CD-1 Mice to Six Predator Odor Components. AB - Mammalian prey species are able to detect predator odors and to display appropriate defensive behavior. However, there is only limited knowledge about whether single compounds of predator odors are sufficient to elicit such behavior. Therefore, we assessed if predator-naive CD-1 mice (n = 60) avoid sulfur-containing compounds that are characteristic components of natural predator odors and/or display other indicators of anxiety. A 2-compartment test arena was used to assess approach/avoidance behavior, general motor activity, and the number of fecal pellets excreted when the animals were presented with 1 of 6 predator odor components in one compartment and a blank control in the other compartment. We found that 2 of the 6 predator odor components (2-propylthietane and 3-methyl-1-butanethiol) were significantly avoided by the mice. The remaining 4 predator odor components (2,2-dimethylthietane, 3-mercapto-3-methylbutan-1-ol, 3-mercapto-3-methylbutyl-1-formate, and methyl-2-phenylethyl sulphide) as well as a nonpredator-associated fruity odor (n-pentyl acetate) were not avoided. Neither the general motor activity nor the number of excreted fecal pellets, both widely used measures of stress- or anxiety-related behavior, were systematically affected by any of the odorants tested. Further, we found that small changes in the molecular structure of a predator odor component can have a marked effect on its behavioral significance as 2-propylthietane was significantly avoided by the mice whereas the structurally related 2,2-dimethylthietane was not. We conclude that sulfur-containing volatiles identified as characteristic components of the urine, feces, and anal gland secretions of mammalian predators can be, but are not necessarily sufficient to elicit defensive behaviors in a mammalian prey species. PMID- 26892311 TI - Self-assembly of supramolecular triarylamine nanowires in mesoporous silica and biocompatible electrodes thereof. AB - Biocompatible silica-based mesoporous materials, which present high surface areas combined with uniform distribution of nanopores, can be organized in functional nanopatterns for a number of applications. However, silica is by essence an electrically insulating material which precludes applications for electro chemical devices. The formation of hybrid electroactive silica nanostructures is thus expected to be of great interest for the design of biocompatible conducting materials such as bioelectrodes. Here we show that we can grow supramolecular stacks of triarylamine molecules in the confined space of oriented mesopores of a silica nanolayer covering a gold electrode. This addressable bottom-up construction is triggered from solution simply by light irradiation. The resulting self-assembled nanowires act as highly conducting electronic pathways crossing the silica layer. They allow very efficient charge transfer from the redox species in solution to the gold surface. We demonstrate the potential of these hybrid constitutional materials by implementing them as biocathodes and by measuring laccase activity that reduces dioxygen to produce water. PMID- 26892313 TI - [A change of eye color]. PMID- 26892315 TI - Megaphone diplomacy fails in junior doctor contract dispute. PMID- 26892312 TI - Comparison of 3 intranasal mists for anesthetizing maxillary teeth in adults: A randomized, double-masked, multicenter phase 3 clinical trial. AB - BACKGROUND: This double-masked, parallel-design, clinical trial assessed whether a combination nasal spray (K305; 3% tetracaine hydrochloride and 0.05% oxymetazoline hydrochloride) compared with a tetracaine-only spray and a placebo spray would be safer and superior in producing local anesthesia sufficient to complete a direct restorative procedure in maxillary nonmolar teeth. METHODS: The authors randomized eligible patients to receive K305 spray (n = 44), tetracaine hydrochloride spray (n = 44), or a placebo solution (n = 22). The authors compared the incidence of the primary efficacy end point-completion of the procedure without rescue local anesthetic-by means of a 1-tailed Fisher exact test. RESULTS: The end point incidence was 84.1% (95% confidence interval [CI], 69.9-93.4) with K305, 27.3% (95% CI, 15.0-42.8) with tetracaine only, and 27.3% (95% CI, 10.7-50.2) with placebo (P < .001 for K305 versus tetracaine only and versus placebo). Combination spray was associated with statistically significant but transient increases in blood pressure. The most frequent adverse events were rhinorrhea and nasal congestion, which resolved within 2 hours after treatment and occurred more often in the K305 group and tetracaine-only group. CONCLUSIONS: In this study population, the K305 combination nasal spray was safe and more effective in attaining pulpal anesthesia of maxillary teeth from premolar to premolar compared with tetracaine-only and placebo sprays. PRACTICAL IMPLICATIONS: The combination nasal spray might represent a valuable alternative to injected local anesthetic for patients undergoing invasive maxillary dental procedures. Clinicaltrials.gov: NCT01710787. PMID- 26892314 TI - L2 Spelling Errors in Italian Children with Dyslexia. AB - The present study aimed to investigate L2 spelling skills in Italian children by administering an English word dictation task to 13 children with dyslexia (CD), 13 control children (comparable in age, gender, schooling and IQ) and a group of 10 children with an English learning difficulty, but no L1 learning disorder. Patterns of difficulties were examined for accuracy and type of errors, in spelling dictated short and long words (i.e. disyllables and three syllables). Notably, CD were poor in spelling English words. Furthermore, their errors were mainly related with phonological representation of words, as they made more 'phonologically' implausible errors than controls. In addition, CD errors were more frequent for short than long words. Conversely, the three groups did not differ in the number of plausible ('non-phonological') errors, that is, words that were incorrectly written, but whose reading could correspond to the dictated word via either Italian or English rules. Error analysis also showed syllable position differences in the spelling patterns of CD, children with and English learning difficulty and control children. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892310 TI - Is the closest facility the one actually used? An assessment of travel time estimation based on mammography facilities. AB - BACKGROUND: Characterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access--which is a critical component of health care planning and equity almost everywhere. METHOD: We analyzed one mammogram from each of 646,553 women participating in the US based Breast Cancer Surveillance Consortium for years 2005-2012. We geocoded each record to street level address data in order to calculate travel time to the closest and to the actually used mammography facility. Travel time between the closest and the actual facility used was explored by woman-level and facility characteristics. RESULTS: Only 35% of women in the study population used their closest facility, but nearly three-quarters of women not using their closest facility used a facility within 5 min of the closest facility. Individuals that by-passed the closest facility tended to live in an urban core, within higher income neighborhoods, or in areas where the average travel times to work was longer. Those living in small towns or isolated rural areas had longer closer and actual median drive times. CONCLUSION: Since the majority of US women accessed a facility within a few minutes of their closest facility this suggests that distance to the closest facility may serve as an adequate proxy for utilization studies of geographically abundant services like mammography in areas where the transportation networks are well established. PMID- 26892316 TI - Mycotoxins in wheat flour and intake assessment in Shandong province of China. AB - In the present study, the occurrence and contamination levels of eight mycotoxins were investigated in wheat flour samples (n = 359) from Shandong Province of China. Samples were determined using a multi-mycotoxin method based on isotope dilution ultrahigh performance liquid chromatography-tandem mass spectrometry. The results indicated that the most frequently found mycotoxins were deoxynivalenol (DON) (97.2%), nivalenol (40.4%) and deoxynivalenol-3-glucoside (33.4%), and mean contamination levels in positive samples were 86.7, 3.55 and 3.34 ug kg(-1), respectively. The obtained data were further used to estimate the daily intake of the local population, and indicated that wheat flour consumption contributes little to DON exposure. However, with the aim to keep the contamination levels under control and to establish a more precise evaluation of the mycotoxin burden in Shandong Province, more sample data from different harvest years and seasons are needed in the future. PMID- 26892317 TI - Association between sleep disorders and injury: a nationwide population-based retrospective cohort study. AB - BACKGROUND: The evidence is insufficient for the association between the exposure of sleep disorders and the risk of injury. The aim of this study was to examine the association between patients with sleep disorders and the risk of injury. METHODS: This was a population-based retrospective cohort study using Taiwan National Health Insurance Research Database from 2005 to 2010. A total of 15 109 patients with sleep disorders were identified as the study cohort. The non-sleep disorders control cohort comprised 29 955 age- and sex-matched patients. We conducted a Cox proportional hazard regression analysis to estimate the effects of sleep disorders on the risk of injury. RESULTS: The overall incidence of injury was 77.03 per 1000 person-years for patients with sleep disorders, which was significantly higher than that of the control cohort (60.63 per 1000 person years). Overall, patients with sleep disorders had a higher risk of injury compared with control cohort (adjusted HR=1.27, 95% CI 1.26 to 1.28). Comparing to the control cohort, patients with insomnia had a 12% higher risk for injury (adjusted HR, 1.12 (95% CI 1.01 to 1.41)). CONCLUSIONS: Comparing to patients with non-sleep disorders, patients with sleep disorders had a higher risk of injury and the risk was particularly pronounced in those who had insomnia. PMID- 26892318 TI - Urinary tract infections in multiple sclerosis. AB - BACKGROUND: Urinary tract infections (UTIs) are commonly reported by people with multiple sclerosis (PwMS) and significantly impact quality of life. OBJECTIVE: To provide an overview of the problem of UTIs in PwMS and offer a practical approach for the diagnosis and management. METHODS: A review of the literature through a Pubmed search up to October 2015 was performed using the following keywords: multiple sclerosis, neurogenic bladder, urinary tract infections, relapse, dipsticks, culture, recurrent and prevention. RESULTS: Noteworthy topics include the definition of a confirmed symptomatic UTI as a positive urine culture defined by >10(5) colony-forming units (CFU)/mL or >10(4) CFU/mL if a urethral catheter urine sample is taken, or any count of bacteria in a suprapubic bladder puncture specimen, both in addition to symptoms including fever, pain, changes in lower urinary tract symptoms or neurological status. Urinalysis is useful to exclude a UTI; however, on its own is insufficient to confirm a UTI, for which urine culture is required. Experts advise asymptomatic UTIs should not be treated except in the context of an acute relapse. From international guidelines, there is no validated strategy to prevent recurrent UTIs in PwMS. CONCLUSION: This review provides an overview of the diagnosis, treatment and prevention of UTIs in the setting of multiple sclerosis (MS). PMID- 26892319 TI - Massive Subcutaneous Emphysema. PMID- 26892321 TI - Capsule Commentary on Reese et al., Two Randomized Controlled Pilot Trials of Social Forces to Improve Statin Adherence Among Patients with Diabetes. PMID- 26892320 TI - Preventable Admissions on a General Medicine Service: Prevalence, Causes and Comparison with AHRQ Prevention Quality Indicators-A Cross-Sectional Analysis. AB - BACKGROUND: Rates of preventable admissions will soon be publicly reported and used in calculating performance-based payments. The current method of assessing preventable admissions, the Agency of Healthcare Research and Quality (AHRQ) Preventable Quality Indicators (PQI) rate, is drawn from claims data and was originally designed to assess population-level access to care. OBJECTIVE: To identify the prevalence and causes of preventable admissions by attending physician review and to compare its performance with the PQI tool in identifying preventable admissions. DESIGN: Cross-sectional survey. SETTING: General medicine service at an academic medical center. PARTICIPANTS: Consecutive inpatient admissions from December 1-15, 2013. MAIN MEASURES: Survey of inpatient attending physicians regarding the preventability of the admissions, primary contributing factors and feasibility of prevention. For the same patients, the PQI tool was applied to determine the claims-derived preventable admission rate. KEY RESULTS: Physicians rated all 322 admissions and classified 122 (38 %) as preventable, of which 31 (25 %) were readmissions. Readmissions were more likely to be rated preventable than other admissions (49 % vs. 35 %, p = 0.04). Application of the AHRQ PQI methodology identified 75 (23 %) preventable admissions. Thirty-one admissions (10 %) were classified as preventable by both methods, and the majority of admissions considered preventable by the AHRQ PQI method (44/78) were not considered preventable by physician assessment (K = 0.04). Of the preventable admissions, physicians assigned patient factors in 54 (44 %), clinician factors in 36 (30 %) and system factors in 32 (26 %). CONCLUSIONS: A large proportion of admissions to a general medicine service appeared preventable, but AHRQ's PQI tool was unable to identify these admissions. Before initiation of the PQI rate for use in pay-for-performance programs, further study is warranted. PMID- 26892322 TI - Diffuse Alveolar Hemorrhage: Blood, Sweat and Tears. PMID- 26892324 TI - Exome sequencing reveals genetic differentiation due to high-altitude adaptation in the Tibetan cashmere goat (Capra hircus). AB - BACKGROUND: The Tibetan cashmere goat (Capra hircus), one of the most ancient breeds in China, has historically been a critical source of meat and cashmere production for local farmers. To adapt to the high-altitude area, extremely harsh climate, and hypoxic environment that the Tibetan cashmere goat lives in, this goat has developed distinct phenotypic traits compared to lowland breeds. However, the genetic components underlying this phenotypic adaptation remain largely unknown. RESULTS: We obtained 118,700 autosomal SNPs through exome sequencing of 330 cashmere goats located at a wide geographic range, including the Tibetan Plateau and low-altitude regions in China. The great majority of SNPs showed low genetic differentiation among populations; however, approximately 2-3% of the loci showed more genetic differentiation than expected under a selectively neutral model. Together with a combined analysis of high- and low-altitude breeds, we revealed 339 genes potentially under high-altitude selection. Genes associated with cardiovascular system development were significantly enriched in our study. Among these genes, the most evident one was endothelial PAS domain protein 1 (EPAS1), which has been previously reported to be involved in complex oxygen sensing and significantly associated with high-altitude adaptation of human, dog, and grey wolf. The missense mutation Q579L that we identified in EPAS1, which occurs next to the Hypoxia-Inducible Factor-1 (HIF-1) domain, was exclusively enriched in the high-altitude populations. CONCLUSIONS: Our study provides insights concerning the population variation in six different cashmere goat populations in China. The variants in cardiovascular system-related genes may explain the observed phenotypic adaptation of the Tibetan cashmere goat. PMID- 26892323 TI - Nanodrug formulations to enhance HIV drug exposure in lymphoid tissues and cells: clinical significance and potential impact on treatment and eradication of HIV/AIDS. AB - Although oral combination antiretroviral therapy effectively clears plasma HIV, patients on oral drugs exhibit much lower drug concentrations in lymph nodes than blood. This drug insufficiency is linked to residual HIV in cells of lymph nodes. While nanoformulations improve drug solubility, safety and delivery, most HIV nanoformulations are intended to extend plasma levels. A stable nanodrug combination that transports, delivers and accumulates in lymph nodes is needed to clear HIV in lymphoid tissues. This review discusses limitations of current oral combination antiretroviral therapy and advances in anti-HIV nanoformulations. A 'systems approach' has been proposed to overcome these limitations. This concept has been used to develop nanoformulations for overcoming drug insufficiency, extending cell and tissue exposure and clearing virus for treating HIV/AIDS. PMID- 26892326 TI - Florbetapir F18 PET Amyloid Neuroimaging and Characteristics in Patients With Mild and Moderate Alzheimer Dementia. AB - BACKGROUND: Clinical diagnosis of Alzheimer disease (AD) is challenging, with a 70.9%-87.3% sensitivity and 44.3%-70.8% specificity, compared with autopsy diagnosis. Florbetapir F18 positron emission tomography (FBP-PET) estimates beta amyloid plaque density antemortem. METHODS: Of 2052 patients (>=55 years old) clinically diagnosed with mild or moderate AD dementia from 2 solanezumab clinical trials, 390 opted to participate in a FBP-PET study addendum. We analyzed baseline prerandomization characteristics. RESULTS: A total of 22.4% had negative FBP-PET scans, whereas 72.5% of mild and 86.9% of moderate AD patients had positive results. No baseline clinical variable reliably differentiated negative from positive FBP-PET scan groups. CONCLUSIONS: These data confirm the challenges of correctly diagnosing AD without using biomarkers. FBP-PET can aid AD dementia differential diagnosis by detecting amyloid pathology antemortem, even when the diagnosis of AD is made by expert clinicians. PMID- 26892325 TI - Diabetes is an independent predictor of right ventricular dysfunction post ST elevation myocardial infarction. AB - BACKGROUND: Diabetes mellitus (DM) is estimated to become the 7th leading cause of death by 2030. Right ventricular dysfunction (RVD) complicating ST elevation myocardial infarction (STEMI) is independently associated with a higher mortality; however the relationship between DM and RVD is currently unknown. The purpose of this study was to determine whether DM is an independent predictor for the presence of right ventricular dysfunction (RVD) post STEMI. METHODS: 106 patients post primary PCI for STEMI were enrolled in the study. Cardiac MRI was performed within 48-72 h after admission in order to assess ventricular function. Statistical analysis consisted initially of descriptive statistics including Chi square, Fisher's exact, or the Wilcoxon rank sum as appropriate. Subsequently, logistic regression analysis was performed to determine independent predictors of RVD. RESULTS: The median age in the study was 58 years (IQR 53, 67). 30 % of the patients had diabetes. Of 99 patients for which RV data was available, 40 had RVD and 59 did not. Patients with DM were significantly more likely to have RVD when compared to those without diabetes (45 vs 22 %, p = 0.03). There was no significant difference in age, hypertension, smoking status, dyslipidemia, serum creatinine or peak CK levels between the two groups. After adjusting for other factors, presence of DM remained an independent predictor for the presence of RV dysfunction (OR 2.78, 95 % CI 1.12, 6.87, p = 0.03). Amongst diabetic patients, those with HbA1C >= 7 % had greater odds of having RVD vs those with HbA1C < 7 % (OR 5.58 (1.20, 25.78), p = 0.02). CONCLUSIONS: The presence of DM conferred an approximately threefold greater odds of being associated with RVD post STEMI. No other major cardiovascular risk factors were independently associated with the presence of RVD. PMID- 26892327 TI - Epileptic Catatonia: A Case Series and Systematic Review. PMID- 26892329 TI - 'There's the record, closed and final': Rough for Theatre II as Psychiatric Encounter. AB - A co-authored collaboration between a theatre practitioner and a clinical psychiatrist, this paper will examine Rough for Theatre II (RFTII) and Beckett's demonstration of the way records are used to understand the human subject. Using Beckett's play to explore interdisciplinary issues of embodiment and diagnosis, the authors will present a dialogue that makes use of the 'best sources' in precisely the same manner as the play's protagonists. One of those sources will be Beckett himself, as Heron will locate the play in its theatrical context through reflections upon his own practice (with Fail Better Productions, UK) as well as recent studies such as Beckett, Technology and the Body (Maude 2009) and Performing Embodiment in Samuel Beckett's Drama (McMullan 2010); another source will be the philosopher Wilhelm Windleband, whose 1901 History of Philosophy was read and noted upon by Beckett in the 1930s, as Broome will introduce a philosophical and psychiatric context to the exchange. Windelband is now a neglected figure in philosophy; but as one of the key figures of Neo-Kantianism in the late 19(th) century, his work was an important impetus to that of Rickert, Weber and Heidegger. Specifically, Windelband gives us the distinction between idiographic and nomothetic understanding of individuals, an approach that is of relevance to the psychiatric encounter. This academic dialogue will consider tensions between subjectivity and objectivity in clinical and performance practice, while examining Beckett's analysis of the use of case notes and relating them back to Windelband's ideas on the understanding of others. The dialogue took place in 2011 at the University of Warwick, and has since been edited by the authors. PMID- 26892328 TI - Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis. AB - BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 * 109 /L) and faecal calprotectin (HR 2.95 for >50 MUg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission. PMID- 26892331 TI - Retroileal colorectal anastomosis after extended left colectomy: application for laparoscopic surgery. AB - Tension-free anastomosis is often difficult to achieve after extended left hemicolectomy because the residual colon is too short to reach the rectal stump. Retroileal colorectal anastomosis is very simple and useful for obtaining tension free anastomosis. We first applied this technique to laparoscopic operations. We herein describe the procedure of laparoscopic retroileal colorectal anastomosis. PMID- 26892330 TI - Dementia-linked amyloidosis is associated with brain protein deamidation as revealed by proteomic profiling of human brain tissues. AB - BACKGROUND: Aggregation of malformed proteins is a key feature of many neurodegenerative diseases, but the mechanisms that drive proteinopathy in the brain are poorly understood. We aimed to characterize aggregated proteins in human brain tissues affected by dementia. RESULTS: To characterize amyloidal plaque purified from post-mortem brain tissue of dementia patient, we applied ultracentrifugation-electrostatic repulsion hydrophilic interaction chromatography (UC-ERLIC) coupled mass spectrometry-based proteomics technologies. Proteomics profiling of both soluble and aggregated amyloidal plaque demonstrated significant enrichment and deamidation of S100A9, ferritin, hemoglobin subunits, creatine kinase and collagen protein among the aggregated brain proteins. Amyloidal plaques were enriched in the deamidated variant of protein S100A9, and structural analysis indicated that both the low- and high affinity calcium binding motifs of S100A9 were deamidated exclusively in the aggregated fraction, suggesting altered charge state and function of this protein in brain tissues affected by dementia. The multiple deamidated residues of S100A9 predicts introduction of negative charge that alter Ca(++) binding, suggesting increased capacity to form pathological aggregates in the brain. CONCLUSION: UC coupled proteomics revealed that brain amyloidal plaques are enriched in deamidated proteins, and suggested that altered charge state and calcium-binding capacity of S100A9 may enhance protein aggregation and promote neurodegeneration in the human brain. PMID- 26892332 TI - Surgical and non-surgical management of repeat pulmonary metastasis from sarcoma following first pulmonary metastasectomy. AB - PURPOSE: Although repeat pulmonary metastasectomy for sarcoma is not uncommon and associated with a favorable survival in select patients, there is a paucity of data on the demographics and tumor characteristics of patients with repeat pulmonary metastasis following complete resection of pulmonary metastases from osteogenic or soft tissue sarcoma. METHODS: A retrospective chart review was performed to identify patients with isolated repeat pulmonary metastasis after complete resection of pulmonary metastases from sarcoma at Kyoto University Hospital between January 1990 and December 2014. Isolated pulmonary metastasis was defined as limited to presumable pulmonary metastasis according to the follow up radiologic workup. RESULTS: Thirty-five patients were identified to have repeat pulmonary metastasis. Thirty patients underwent attempted repeat pulmonary metastasectomy (including 21 undergoing documented complete resection and 7 undergoing documented incomplete or aborted resections). Five patients received non-surgical management. The median follow-up period was 16 months (range 1-234) from repeat pulmonary metastasis. The five-year overall survival of the whole patient cohort and those undergoing repeat pulmonary metastasectomy were 37.6 and 41.1 %, respectively, from repeat pulmonary metastasis. CONCLUSIONS: A majority of patients with repeat pulmonary metastasis from sarcoma undergo repeat metastasectomy, which is associated with favorable survival outcomes. However, a greater accumulation of data on non-surgically managed patients is needed as such information is currently limited available. PMID- 26892333 TI - A family planning clinic-based intervention to address reproductive coercion: a cluster randomized controlled trial. AB - OBJECTIVE: We assessed the effectiveness of a provider-delivered intervention targeting reproductive coercion, an important factor in unintended pregnancy. STUDY DESIGN: We randomized 25 family planning clinics (17 clusters) to deliver an education/counseling intervention or usual care. Reproductive coercion and partner violence victimization at 1 year follow-up were primary outcomes. Unintended pregnancy, recognition of sexual and reproductive coercion, self efficacy to use and use of harm reduction behaviors to reduce victimization and contraception nonuse, and knowledge and use of partner violence resources were secondary outcomes. Analyses included all available data using an intention-to treat approach. RESULTS: Among 4009 females ages 16 to 29 years seeking care, 3687 completed a baseline survey prior to clinic visit from October 2011 to November 2012; 3017 provided data at 12-20weeks post-baseline (T2) and 2926 at 12months post-baseline (T3) (79% retention). Intervention effects were not significant for reproductive coercion [adjusted risk ratio (ARR) 1.50 (95% confidence interval 0.95-2.35)] or partner violence [ARR 1.07 (0.84-1.38)]. Intervention participants reported improved knowledge of partner violence resources [ARR 4.25 (3.29-5.50)] and self-efficacy to enact harm reduction behaviors [adjusted mean difference 0.06 (0.02-0.10)]. In time point-specific models which included moderating effects of exposure to reproductive coercion at baseline, a higher reproductive coercion score at baseline was associated with a decrease in reproductive coercion 1 year later (T3). Use and sharing of the domestic violence hotline number also increased. CONCLUSION: This brief clinic intervention did not reduce partner violence victimization. The intervention enhanced two outcomes that may increase safety for women, specifically awareness of partner violence resources and self-efficacy to enact harm reduction behaviors. It also appeared to reduce reproductive coercion among women experiencing multiple forms of such abuse. PMID- 26892334 TI - Detection of metastatic tumors after gamma-irradiation using longitudinal molecular imaging and gene expression profiling of metastatic tumor nodules. AB - A few recent reports have indicated that metastatic growth of several human cancer cells could be promoted by radiotherapy. C6-L cells expressing the firefly luciferase (fLuc) gene were implanted subcutaneously into the right thigh of BALB/c nu/nu mice. C6-L xenograft mice were treated locally with 50-Gy gamma irradiation (gamma-IR) in five 10-Gy fractions. Metastatic tumors were evaluated after gamma-IR by imaging techniques. Total RNA from non-irradiated primary tumor (NRPT), gamma-irradiated primary tumor (RPT), and three metastatic lung nodule was isolated and analyzed by microarray. Metastatic lung nodules were detected by BLI and PET/CT after 6-9 weeks of gamma-IR in 6 (17.1%) of the 35 mice. The images clearly demonstrated high [18F]FLT and [18F]FDG uptake into metastatic lung nodules. Whole mRNA expression patterns were analyzed by microarray to elucidate the changes among NRPT, RPT and metastatic lung nodules after gamma-IR. In particular, expression changes in the cancer stem cell markers were highly significant in RPT. We observed the metastatic tumors after gamma-IR in a tumor bearing animal model using molecular imaging methods and analyzed the gene expression profile to elucidate genetic changes after gamma-IR. PMID- 26892335 TI - Family planning, antenatal and delivery care: cross-sectional survey evidence on levels of coverage and inequalities by public and private sector in 57 low- and middle-income countries. AB - OBJECTIVE: The objective of this study was to assess the role of the private sector in low- and middle-income countries (LMICs). We used Demographic and Health Surveys for 57 countries (2000-2013) to evaluate the private sector's share in providing three reproductive and maternal/newborn health services (family planning, antenatal and delivery care), in total and by socio-economic position. METHODS: We used data from 865 547 women aged 15-49, representing a total of 3 billion people. We defined 'met and unmet need for services' and 'use of appropriate service types' clearly and developed explicit classifications of source and sector of provision. RESULTS: Across the four regions (sub-Saharan Africa, Middle East/Europe, Asia and Latin America), unmet need ranged from 28% to 61% for family planning, 8% to 22% for ANC and 21% to 51% for delivery care. The private-sector share among users of family planning services was 37-39% across regions (overall mean: 37%; median across countries: 41%). The private sector market share among users of ANC was 13-61% across regions (overall mean: 44%; median across countries: 15%). The private-sector share among appropriate deliveries was 9-56% across regions (overall mean: 40%; median across countries: 14%). For all three healthcare services, women in the richest wealth quintile used private services more than the poorest. Wealth gaps in met need for services were smallest for family planning and largest for delivery care. CONCLUSIONS: The private sector serves substantial numbers of women in LMICs, particularly the richest. To achieve universal health coverage, including adequate quality care, it is imperative to understand this sector, starting with improved data collection on healthcare provision. PMID- 26892337 TI - Use of scientific social networking to improve the research strategies of PubMed readers. AB - BACKGROUND: Keeping up with journal articles on a daily basis is an important activity of scientists engaged in biomedical research. Usually, journal articles and papers in the field of biomedicine are accessed through the Medline/PubMed electronic library. In the process of navigating PubMed, researchers unknowingly generate user-specific reading profiles that can be shared within a social networking environment. This paper examines the structure of the social networking environment generated by PubMed users. METHODS: A web browser plugin was developed to map [in Medical Subject Headings (MeSH) terms] the reading patterns of individual PubMed users. RESULTS: We developed a scientific social network based on the personal research profiles of readers of biomedical articles. A browser plugin is used to record the digital object identifier or PubMed ID of web pages. Recorded items are posted on the activity feed and automatically mapped to PubMed abstract. Within the activity feed a user can trace back previously browsed articles and insert comments. By calculating the frequency with which specific MeSH occur, the research interests of PubMed users can be visually represented with a tag cloud. Finally, research profiles can be searched for matches between network users. CONCLUSIONS: A social networking environment was created using MeSH terms to map articles accessed through the Medline/PubMed online library system. In-network social communication is supported by the recommendation of articles and by matching users with similar scientific interests. The system is available at http://bioknol.org/en/. PMID- 26892336 TI - Simultaneous occurrence of fibrillary glomerulonephritis and renal lesions in nonmalignant monoclonal IgM gammopathy. AB - BACKGROUND: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that seldom coexists with other diseases. Membranoproliferative glomerulonephritis is a pathologic finding of renal lesions associated with IgM secreting monoclonal proliferations. We present a case study of a patient with unusual simultaneous FGN and IgM-related renal disorder in nonmalignant monoclonal IgM gammopathy. CASE PRESENTATION: A 63-year-old male presented with nephrotic syndrome and elevated serum creatinine levels. Laboratory examination revealed elevated levels of serum IgM and low C3 levels. Serum and urine immunofixation electrophoresis showed a monoclonal IgM with a kappa light chain. A bone marrow biopsy revealed less than 5 % bone marrow infiltration by lymphoplasmacytic lymphoma, and a renal biopsy revealed mesangiocapillary glomerulonephritis on light microscopy. Immunofluorescent and immunohistochemical staining indicated granular deposits of immunoglobulin G in the mesangium and granular deposits of immunoglobulin M and kappa light chains along the capillary wall. Electron microscopy revealed randomly arranged nonbranching fibrils of approximately 15 nm in diameter in the glomerular mesangium and subendothelial electron-dense deposits. According to these results, we confirmed FGN and membranoproliferative glomerulonephritis, which were attributed to monoclonal IgM deposits. CONCLUSION: To the best of our knowledge, this is the first report of simultaneous FGN and membranoproliferative glomerulonephritis in nonmalignant IgM monoclonal gammopathy. PMID- 26892339 TI - Common trajectories of physical functioning in the Doetinchem Cohort Study. AB - PURPOSE: to describe common trajectories of physical functioning and their determinants among an adult cohort, followed over a period of 15 years. METHODS: the study sample consisted of 4,123 participants (initial ages 26-70 years) from the Doetinchem Cohort Study, who participated in three or four measurement cycles. Physical functioning was measured with the Dutch version of the SF-36. Using a group-based modelling strategy, trajectories of physical functioning were determined. Weighted multinomial logistic regression analyses were performed to identify socio-demographic, lifestyle and health characteristics that differentiate between the trajectories at baseline. RESULTS: five common physical functioning trajectories were distinguished, labelled as 'stable not limited' (27% of the population), 'stable slightly limited' (54%), 'slightly limited substantial deterioration' (7%), 'moderately limited gradual improvement' (9%) and 'stable severely limited' (3%). The characteristics that differentiate between the trajectories with limitations and the trajectory 'stable not limited' were being female, older, physically inactive, overweight or obese, having one or more chronic conditions, poor mental health and poor self-perceived health at baseline. Being younger, physically active, less obese, living with a partner and a good perceived health were characteristics of the trajectory 'moderately limited gradual improvement' compared with 'stable severely limited'. CONCLUSION: five common trajectories of physical functioning were distinguished in an adult cohort, with most individuals following a stable but slightly limited course of physical functioning. Some early risk indicators were found that in the future might be used to early identify those with limitations in physical functioning. PMID- 26892338 TI - Aqueous Extracts of Hibiscus sabdariffa Calyces to Control Aichi Virus. AB - Aqueous Hibiscus sabdariffa extracts possess antimicrobial properties with limited information available on their antiviral effects. Aichi virus (AiV) is an emerging foodborne pathogen that causes gastroenteritis. Vaccines are currently unavailable to prevent their disease transmission. The objective of this study was to determine the antiviral effects of aqueous H. sabdariffa extracts against AiV. AiV at ~5 log PFU/ml was incubated with undiluted (200 mg/ml), 1:1 (100 mg/ml) or 1:5 (40 mg/ml) diluted aqueous hibiscus extract (pH 3.6), phosphate buffered saline (pH 7.2 as control), or malic acid (pH 3.0, acid control) at 37 degrees C over 24 h. Treatments were stopped by serially diluting in cell-culture media containing fetal bovine serum and titers were determined using plaque assays on confluent Vero cells. Each treatment was replicated thrice and assayed in duplicate. AiV did not show any significant reduction with 1:1 (100 mg/ml) or 1:5 (40 mg/ml) diluted aqueous hibiscus extracts or malic acid after 0.5, 1, or 2 h at 37 degrees C. However, AiV titers were reduced to non-detectable levels after 24 h with all the three tested concentrations, while malic acid showed only 0.93 log PFU/ml reduction after 24 h. AiV was reduced by 0.5 and 0.9 log PFU/ml with undiluted extracts (200 mg/ml) after 2 and 6 h, respectively. AiV treated with 1:1 (100 mg/ml) and 1:5 (40 mg/ml) diluted extracts showed a minimal ~0.3 log PFU/ml reduction after 6 h. These extracts show promise to reduce AiV titers mainly through alteration of virus structure, though higher concentrations may have improved effects. PMID- 26892341 TI - RFT1-congenital disorder of glycosylation (CDG) syndrome: a cause of early-onset severe epilepsy. AB - RFT1-congenital disorder of glycosylation (CDG) syndrome, a recessive N glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online]. PMID- 26892340 TI - Scanning for alpha-Hemoglobin Variants by High-Resolution Melting Analysis. AB - BACKGROUND: Definitive detection of hemoglobin (Hb) variants requires DNA sequencing. High-resolution melting (HRM) analysis of polymerase chain reaction (PCR) amplicons was applied to detect and discriminate among uncommon alpha-Hb variants found in Thailand. METHODS: Uncommon suspected alpha-Hb variants observed in Hb typing were identified by sequencing of DNA from whole blood samples. Three pairs of PCR primers covering the mutation regions in the three alpha-globin exons then were used for PCR coupled with difference in HRM analysis to subtract out the concomitant melting profile of the normal allele in the heterozygous state. RESULTS: DNA sequencing identified six heterozygous alpha-Hb variants, namely, Hb G-Waimanalo (HBA2: exon 2, codon 64 G>A), Hb J-Buda (HBA1: exon 2, codon 61 G>T), Hb Kurosaki (HBA2: exon 1; codon 7 A>G), Hb O-Indonesia (HBA1: exon 3 codon 116 G>A), Hb Q-India (HBA1:exon 2, codon 64 G>C), and Hb Q Thailand (HBA1: exon 2 codon 74 G>C). Difference HRM analysis showed one temperature melting profile using exon 1 primer pair, four different profiles with exon 2 primer pair, and one profile with exon 3 primer pair. CONCLUSIONS: PCR-HRM analysis was effective in detecting and discriminating among single point mutations causing six uncommon alpha-Hb variants in heterozygous individuals. The method can be applied for routine screening due to its simplicity and relatively low cost. PMID- 26892342 TI - Distinct courses of infection with Leishmania (L.) amazonensis are observed in BALB/c, BALB/c nude and C57BL/6 mice. AB - Leishmania (L.) amazonensis [L. (L.) amazonensis] is widely distributed in Brazil and its symptomatic infections usually lead to few localized lesions and sometimes to diffuse cutaneous form, with nodules throughout the body, anergy to parasite antigens and poor therapeutic response. The variability of these manifestations draws attention to the need for studies on the pathophysiology of infection by this species. In this study, we analysed the course and immunological aspects of L. (L.) amazonensis infection in BALB/c and C57BL/6 strains, both susceptible, but displaying different clinical courses, and athymic BALB/c nude, to illustrate the role of T cell dependent responses. We analysed footpad thickness and parasite burden by in vivo imaging. Furthermore, we evaluated the cellular profile and cytokine production in lymph nodes and the inflammatory infiltrates of lesions. Nude mice showed delayed lesion development and less inflammatory cells in lesions, but higher parasite burden than BALB/c and C57BL/6. BALB/c and C57BL/6 mice had similar parasite burdens, lesion sizes and infiltrates until 6 weeks after infection, and after that C57BL/6 mice controlled the infection. Small differences in parasite numbers were observed in C57BL/6 macrophages in vitro, indicating that in vivo milieu accounts for most differences in infection. We believe our results shed light on the role of host immune system in the course of L. (L.) amazonensis infection by comparing three mouse strains that differ in parasitaemia and inflammatory cells. PMID- 26892344 TI - Measuring motivation for medical treatment: confirming the factor structure of the Achievement Motivation Index for Medical Treatment (AMI-MeT). AB - BACKGROUND: Developments in chemotherapy have led to changes in cancer care in Japan, with the government promoting a transition to outpatient chemotherapy. This requires patients and their families to participate more actively in treatment than in the past. However, it remains unclear how patients' motivation for medical treatment affects clinical consultations with their physicians. To investigate this, we developed a psychological index called the Achievement Motive Index for Medical Treatment (AMI-MeT), which comprises self-derived achievement motivation (AMS) and achievement motivation derived from others (AMO). However, its factor structure has not yet been confirmed in populations other than healthy university students. Thus, the aims of this study were to confirm the factor structure of the AMI-MeT in other groups and to determine the convergent and divergent validity of the AMI-MeT. METHODS: The AMI-MeT was administered to university students (n = 414), apparently healthy workers (n = 154), and cancer patients (n = 51). Multi-group confirmatory factor analysis was conducted and the mean scores of the AMI-MeT were compared between the groups. Correlations between the AMI-MeT and the Self-Construal Scale, comprising independent self-construal (IndSC) and interdependent self-construal (InterSC) subscales, were investigated in another group of students (n = 335). RESULTS: The multi-group confirmatory factor analysis supported a two-factor structure of the AMI-MeT: the weak invariance model was the best fit for the data. The mean scores of the AMI-MeT in apparently healthy workers and cancer patients were significantly higher than that in students (P < .01). The correlation analysis revealed that AMS scores were associated with IndSC scores (r = .25, P < .01) and AMO scores with InterSC scores (r = .30, P < .01). CONCLUSION: The two-factor model of the AMI-MeT was deemed appropriate for all three groups, and the subscales of the AMI-MeT successfully reflected the self and other dimensions. The AMI-MeT appears to be an effective tool for measuring medical treatment motivation, making it useful in participant observational research on medical consultations for Japanese cancer treatment. PMID- 26892343 TI - Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation. AB - Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-beta stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF beta. PMID- 26892345 TI - De novo 14q24.2q24.3 microdeletion including IFT43 is associated with intellectual disability, skeletal anomalies, cardiac anomalies, and myopia. AB - We report an 11-year-old girl with mild intellectual disability, skeletal anomalies, congenital heart defect, myopia, and facial dysmorphisms including an extra incisor, cup-shaped ears, and a preauricular skin tag. Array comparative genomic hybridization analysis identified a de novo 4.5-Mb microdeletion on chromosome 14q24.2q24.3. The deleted region and phenotype partially overlap with previously reported patients. Here, we provide an overview of the literature on 14q24 microdeletions and further delineate the associated phenotype. We performed exome sequencing to examine other causes for the phenotype and queried genes present in the 14q24.2q24.3 microdeletion that are associated with recessive disease for variants in the non-deleted allele. The deleted region contains 65 protein-coding genes, including the ciliary gene IFT43. Although Sanger and exome sequencing did not identify variants in the second IFT43 allele or in other IFT complex A-protein-encoding genes, immunocytochemistry showed increased accumulation of IFT-B proteins at the ciliary tip in patient-derived fibroblasts compared to control cells, demonstrating defective retrograde ciliary transport. This could suggest a ciliary defect in the pathogenesis of this disorder. (c) 2016 Wiley Periodicals, Inc. PMID- 26892347 TI - Mathematical Modeling of the Biomarker Milieu to Characterize Preterm Birth and Predict Adverse Neonatal Outcomes. AB - PROBLEM: To identify preterm neonates at risk for adverse neonatal outcomes. METHOD OF STUDY: A nested case-control study from the prospectively followed Boston Birth Cohort of mother-neonate pairs was performed. A classification model for preterm-born neonates was derived from 27 cord blood biomarkers using orthogonal projections to latent structures discriminant analysis. Predictive relationships were made between biomarkers and adverse outcomes using logistic regression. RESULTS: From 926 births (53% of which were preterm), using weighted values for 27 biomarkers, a score was created that classified 73% of preterm deliveries. Soluble TNF-R1, NT-3, MCP-1, BDNF, IL-4, MMP-9, TREM-1, TNF-alpha, IL 5 and IL-10 were most influential. Our model was more sensitive for birth <34 weeks (sensitivity 89.5%, specificity 76.9%). IL-10, TNF-alpha, BDNF, NT-3, MMP 9, sTNF-R1 and MCP-1 were significantly predictive of NEC, IVH, sepsis and infections. CONCLUSION: We developed a novel mathematical model of 27 biomarkers associated with adverse neonatal outcomes in neonates born preterm. PMID- 26892346 TI - TRPC6 G757D Loss-of-Function Mutation Associates with FSGS. AB - FSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of FSGS have been linked to mutations in the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene encoding a nonselective cation channel. Most of these TRPC6 mutations cause a gain-of function phenotype, leading to calcium-triggered podocyte cell death, but the underlying molecular mechanisms are unclear. We studied the molecular effect of disease-related mutations using tridimensional in silico modeling of tetrameric TRPC6. Our results indicated that G757 is localized in a domain forming a TRPC6 TRPC6 interface and predicted that the amino acid exchange G757D causes local steric hindrance and disruption of the channel complex. Notably, functional characterization of model interface domain mutants suggested a loss-of-function phenotype. We then characterized 19 human FSGS-related TRPC6 mutations, the majority of which caused gain-of-function mutations. However, five mutations (N125S, L395A, G757D, L780P, and R895L) caused a loss-of-function phenotype. Coexpression of wild-type TRPC6 and TRPC6 G757D, mimicking heterozygosity observed in patients, revealed a dominant negative effect of TRPC6 G757D. Our comprehensive analysis of human disease-causing TRPC6 mutations reveals loss of TRPC6 function as an additional concept of hereditary FSGS and provides molecular insights into the mechanism responsible for the loss-of-function phenotype of TRPC6 G757D in humans. PMID- 26892348 TI - Longitudinal study of caries progression in 2- and 3-year-old German children. AB - OBJECTIVE: This 2-year longitudinal study in 2- and 3-year-old kindergarten children investigated lesion progression on different surfaces of primary teeth. METHODS: The study was conducted between September 2008 and September 2010 on a sample of 400 children from the Kyffhauser district (Thuringia, Germany). A calibrated investigator recorded (non)cavitated caries lesions according to World Health Organization (WHO), International Caries Detection and Assessment System (ICDAS) and Universal Visual Scoring System (UniViSS) criteria. Nonparametric methods and linear regression using a mixed-effects model with an unbalanced design were used for data analysis. RESULTS: There was a significant increase in the prevalence of noncavitated caries lesions during the 2-year period, with the highest chance for change on all surfaces compared to cavitated lesions. First visible sign lesions on occlusal surfaces had the highest chance for change (estimate 0.38), whereas established lesions revealed the highest chance for change on proximal (estimate 1.05) and smooth surfaces (estimate 0.62). Proximal lesions exhibited the greatest chance for change irrespective of severity level. CONCLUSION: Our study demonstrated that each type of carious lesion had different changing rates. Greater lesion severity correlated with greater chances to change and receive treatment. This information is crucial for dental practitioners in decision-making processes. PMID- 26892349 TI - Intra- and interspecies gene expression models for predicting drug response in canine osteosarcoma. AB - BACKGROUND: Genomics-based predictors of drug response have the potential to improve outcomes associated with cancer therapy. Osteosarcoma (OS), the most common primary bone cancer in dogs, is commonly treated with adjuvant doxorubicin or carboplatin following amputation of the affected limb. We evaluated the use of gene-expression based models built in an intra- or interspecies manner to predict chemosensitivity and treatment outcome in canine OS. Models were built and evaluated using microarray gene expression and drug sensitivity data from human and canine cancer cell lines, and canine OS tumor datasets. The "COXEN" method was utilized to filter gene signatures between human and dog datasets based on strong co-expression patterns. Models were built using linear discriminant analysis via the misclassification penalized posterior algorithm. RESULTS: The best doxorubicin model involved genes identified in human lines that were co expressed and trained on canine OS tumor data, which accurately predicted clinical outcome in 73 % of dogs (p = 0.0262, binomial). The best carboplatin model utilized canine lines for gene identification and model training, with canine OS tumor data for co-expression. Dogs whose treatment matched our predictions had significantly better clinical outcomes than those that didn't (p = 0.0006, Log Rank), and this predictor significantly associated with longer disease free intervals in a Cox multivariate analysis (hazard ratio = 0.3102, p = 0.0124). CONCLUSIONS: Our data show that intra- and interspecies gene expression models can successfully predict response in canine OS, which may improve outcome in dogs and serve as pre-clinical validation for similar methods in human cancer research. PMID- 26892350 TI - Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion. AB - Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has been demonstrated to have significant effects on tumor migration by previous studies, but its specific contribution to hepatocellular carcinoma (HCC) is currently unknown. The aim of this study was to evaluate the prognostic value of TRIM16 and investigate its functional roles in HCC. The expression of TRIM16 in HCC patient samples were examined using qRT-PCR and western blotting. HCC cell lines with either TRIM16 overexpression or knockdown were established. The effect of TRIM16 on HCC cell migration and invasion was investigated using these cells. Compared with paired normal liver tissues in clinical cancer samples, we found that the expression of TRIM16 was significantly downregulated in HCC lesions. We also found knockdown of TRIM16 promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. Mechanistically, TRIM16 inhibited ZEB2 expression, which in turn inhibited transcription of the pivotal ZEB2 target gene E-cadherin. RNA interference-mediated silencing of ZEB2 attenuated shTRIM16 enhanced cell migration and invasion. In conclusion, our findings define TRIM16 as an inhibitor of EMT and metastasis in HCC that predicts poor clinical outcomes. PMID- 26892351 TI - Influence of supragingival biofilm control and smoking habit on Interleukin-1beta concentration. AB - This investigation compared gingival crevicular fluid (GCF) interleukin-1beta (IL 1beta) concentrations in periodontitis patients subjected to a strict supragingival biofilm control (Supra) for 6 months. Never-smokers (23) and smokers (n = 20; 19.6 +/- 11.8 cigarettes/day) moderate-to-severe chronic periodontitis patients underwent a 6 months period of supragingival control with weekly recall visits. Periodontal probing depth (PPD), bleeding on probing (BOP) and GCF samples (from different PPD category sites: 3-5 mm and 6-10 mm) were obtained at the baseline, 30, and 180 days. IL-1beta was assessed by enzyme linked immunosorbent assay. Generalized estimating equations were used to fit prediction models of IL-1beta changes, considering the dependence between the examinations, and using only data from experimental sites. Overall IL-1beta concentrations decreased from 3.2 pg/uL to 1.9 pg/uL. Higher baseline IL-1beta concentrations were associated with higher baseline PPD values in both groups. There were no differences in IL-1beta concentrations between never-smokers and smokers over time for any PPD category. Higher baseline PPD values and the presence of BOP on day 180 were significantly associated with higher IL-1beta concentrations. A strict Supra regimen reduced IL-1beta concentrations over time in periodontitis patients. The benefits observed for smokers underline the importance of oral hygiene measures, even considering the presence of this important risk factor. PMID- 26892352 TI - Fluoride stability in dentifrices stored in schools in a town of northern Brazil. AB - The aim of this study was to analyze fluoride stability in dentifrices stored during nine months in schools from Careiro da Varzea, State of Amazonas, Brazil. Analysis of total fluoride concentration, total soluble fluoride, and ionic fluoride in the dentifrice samples was performed in four different time periods: at the time of purchase (baseline); after three months, after six months, and after nine months of storage. Fluoride concentration was determined using a specific electrode (Orion 96-09) connected to an ion analyzer (Orion A-720) and calibrated with fluoride standard solutions containing 2.0 to 32.0 ppm F. The results obtained during the measurements were analyzed by analysis of variance (one-way ANOVA), followed by Tukey's test for comparison of the means. After nine months of storage, total soluble fluoride, the active form of fluoride, decreased by 21.9%. As total soluble fluoride was below the minimum required for anticaries efficacy (1,000 ppm F) in the fourth analysis, it may be concluded that anticaries potential decreased with storage time. PMID- 26892353 TI - Digital panoramic radiography for diagnosis of the temporomandibular joint: CBCT as the gold standard. AB - Three-dimensional imaging modalities have been reported to be more accurate than panoramic radiographs (PR) for the assessment of bone components of the temporomandibular joint (TMJ). No exact prior information is available that demonstrates which specific limitations occur in terms of TMJ diagnosis when using PR for this purpose. This study aimed to assess the clinical validity of digital panoramic radiography (DPR) when diagnosing morphological disorders of the TMJ using cone-beam computed tomography (CBCT) images as the gold standard. A sample composed of TMJ images (N = 848), including 212 DPR and 212 CBCT images obtained from the same patient, was used to assess any morphological changes in the TMJ. Four appraisers diagnosed all of the DPR images, whereas the CBCT images were used to establish the gold standard. The reliability of each appraiser's response pattern was analyzed using the Kappa test (kappa), and diagnostic tests were performed to assess each appraiser's performance using a significance level setting of 5% (alpha = 0.05). Reliability of each appraiser's response pattern compared to the gold standard ranged from a slight-to-moderate agreement (0.18 <= kappa <= 0.45); and among the different appraisers, the response pattern showed a fair agreement (0.22 <= kappa <= 0.39). Diagnostic tests showed a wide range among the different possible morphological changes diagnosed. DPR does not have validity when diagnosing morphological changes in the TMJ; it underestimates the radiological findings with higher prevalence, and thus, it cannot be used effectively as a diagnostic tool for bone components within this region. PMID- 26892354 TI - Dental caries and social factors: impact on quality of life in Brazilian children. AB - The objective of this study was to evaluate the impact of dental caries and social determinants in the Oral Health Related Quality of Life (OHRQoL) of children in Belo Horizonte, Brazil. This is a population-based cross-sectional study with a representative sample of 1,204 children aged 8 to 10 years randomly selected from 19 public and private schools. The children were clinically examined at school by two trained and calibrated examiners (Kappa = 0.78 - 1.00). The Decayed, Missing and Filled Teeth Index (DMF-T and dmf-t) was used for the diagnosis of dental caries. The social factors were determined by parents'/caregivers' schooling, household income, number of people in the household, type of school, and by the Social Vulnerability Index. The Brazilian version of the Child Perceptions Questionnaire for ages 8 to 10 years was used to assess the impact on quality of life. A total of 278 (23.1%) out of 1,204 children had at least one cavitated carious lesion and 47.0% presented a negative impact on OHRQoL. In the final multivariate Poisson's regression model, household income and presence of untreated dental caries were statistically associated with a negative impact on OHRQoL (p < 0.001).Children with dental caries and from low income families had a higher negative impact on OHRQoL. PMID- 26892355 TI - Influence of polymeric matrix on the physical and chemical properties of experimental composites. AB - Nowadays, the main reasons for replacement of resin-based composite restorations are fracture or problems with the integrity of their interface, such as marginal staining, microleakage, or secondary caries. The aim of the present study was to evaluate the influence of the organic matrix on polymerization stress (PS), degree of conversion (DC), elastic modulus (E), flexural strength (FS), Knoop hardness (KHN), sorption (SP), and solubility (SL). In order to obtain a material which combines better mechanical properties with lower PS, seven experimental composites were prepared using BisGMA to TEGDMA molar ratios of 2:8, 3:7, 4:6, 5:5, 6:4, 7:3 and 8:2 and 40% of silica. PS was obtained in a universal testing machine, using acrylic as bonding substrate. DC was determined using Fourier Transform Raman spectroscopy. E and FS were obtained by the three-point bending test. KHN was measured by a microindentation test using a load of 25 g for 30 s. SP and SL were assessed according to ISO 4049. The data were submitted to one-way ANOVA. The increase in BisGMA concentration resulted in the decrease of PS, DC, E, FS and KHN. However, it did not change the SP and SL values. FS, E and KHN showed a strong and direct relationship with the DC of the materials. The composite material with a BisGMA to TEGDMA molar ratio of 1:1 was the one with better mechanical properties and lower PS. PMID- 26892356 TI - How erosive drinks and enzyme inhibitors impact bond strength to dentin. AB - Concern has been raised about the bonding of restorative procedures to an erosive lesion, given the change in organic and inorganic composition and structure of this substrate. This in vitro study evaluated the effect of erosive drinks and an enzyme inhibitor (2% chlorhexidine digluconate - 2% CHX) on bond strength to dentin. Sixty sound human third molars were selected, and the occlusal enamel was flattened, exposing the dentin surface. The specimens were randomly divided into three groups: AS-Artificial saliva (control group), RC- Regular Cola and ZC- Zero Cola. Twenty specimens were immersed in their respective solution for 1 minute, 3 times a day, over the course of 5 days. After acid etching and before bonding with Adper Single Bond 2, half of the samples of each group (n = 10) were treated with 2% CHX, whereas the other half (n = 10) were not, forming the control group (CONV). All the specimens were restored with Filtek Z250 composite resin filled in Tygon tubes (0.48 mm2), yielding six microcylinders for microshear bond strength testing. Three composite resin microcylinders of each specimen were tested after 1 month, and the remaining microcylinders were tested after 6 months. Failure modes were determined using a stereomicroscope (40x). The data were statistically analyzed by three-way ANOVA and Tukey tests (alpha = 0.05). Overall bonding was reduced after 6 months, regardless of treatment. The 2% CHX enhanced bond strength after 1 month only in the ZC group, and did not enhance bonding performance to demineralized dentin by erosive protocol after 6 months in any group. PMID- 26892357 TI - Quantitative ultrasound at the hand phalanges in patients with bisphosphonate related osteonecrosis of the jaws. AB - Patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) who received intravenous or oral bisphosphonates (BP) were selected for determination of their bone microarchitecture as a risk predictor of BRONJ development. The diagnosis of BRONJ was made based on clinical and radiographic findings. The control group consisted of healthy patients. All patients underwent quantitative and qualitative ultrasound measurements of bone at the hand phalanges carried out using the DBM Sonic BP. Ultrasound bone profile index (UBPI), amplitude-dependent speed of sound (AD-SoS), bone biophysics profile (BBP), and bone transmission time (BTT) were measured. The BRONJ group consisted of 17 patients (62 +/- 4.24; range: 45-82); 10 (58.8%) were male and seven (41.1%) were female, of whom 11 (64.7%) suffered from multiple myeloma, three (17.6%) from osteoporosis, one (5.8%) from prostate cancer, one (5.8%) from kidney cancer, and one (5.8%) from leukemia. Fourteen (82.3%) of them received intravenous BP whereas three (17.6%) received oral BP. Nine (9/17; 52.9%) patients developed bone exposure: two in the maxilla and seven in the mandible. Regarding quantitative parameters, Ad-SoS was low in the BRONJ group, but not significant. The UBPI score was significantly reduced in BRONJ patients with exposed bone when compared to controls (0.47 +/- 0.12 vs. 0.70 +/- 0.15; p = 0.004). The present study demonstrated that quantitative ultrasound was able to show bone microarchitecture alterations in BRONJ patients, and suggests that these analyses may be an important tool for early detection of bone degeneration associated with BRONJ. PMID- 26892358 TI - Antimicrobial efficacy of the EndoVac system plus PDT against intracanal Candida albicans: an ex vivo study. AB - This study evaluated the ex vivoantimicrobial efficacy of the EndoVac system and the photodynamic therapy (PDT) associated with chemomechanical debridement (CMD) and intracanal medication on Candida albicans. Seventy-eight sterile premolars were contaminated withC. albicans (ATCC 21433) for 30 days. The teeth were randomly assigned into four groups: Control (CMD with conventional irrigation); Endovac (CMD with EndoVac system); PDT (CMD with conventional irrigation and PDT); and Endovac + PDT (CMD with EndoVac and PDT). After the therapies, intracanal dressing (calcium hydroxide) was applied to all teeth for seven days. Samples were obtained before (T1) and after the therapeutic procedures (T2), and after intracanal medication (T3), plated onto BHI agar and incubated (37 degrees C, 48 h) to determine the colony-forming units (CFU)/mL. The overall mean level ofC. albicans at baseline was relatively high (1.85 x 106 +/- 2.7 x 106 CFU mL 1). A significant reduction of C. albicans(p < 0.05) was observed over time (T1 to T2 and T1 to T3) in all groups. An additional significant reduction from T2 to T3 was observed only in the Endovac group (p < 0.05). No differences in mean reduction of C. albicans were observed among groups. However, the Endovac group presented the lowest mean counts of C. albicans at T3, whereas the PDT group had the highest counts of this microorganism (p < 0.05). The EndoVac system of irrigation/aspiration associated with CMD was the most effective therapeutic protocol for reducing intracanal levels of C. albicans. PDT showed a very limited efficacy against this species. PMID- 26892359 TI - Oral midazolam reduces cortisol levels during local anaesthesia in children: a randomised controlled trial. AB - Little is known about whether midazolam sedation can reduce salivary cortisol levels and consequently influence children's behaviour during dental treatment. The aim of this study was to evaluate the effect of midazolam sedation on salivary cortisol and its correlation with children's behaviour during restorative dental treatment. Eighteen healthy children, aged two to five years, were randomly assigned to two dental treatment appointments, both with physical restraint: oral midazolam 1 mg/kg (MS) and placebo (PS). An observer assessed the children's behaviour (videos) using the Ohio State University Behavioral Rating Scale (OSUBRS). The children's saliva was collected just after waking up, on arrival at the dental school, 25 minutes after local anaesthesia, and 25 minutes after the end of the procedure. Salivary cortisol levels were determined using the enzyme-linked immunoabsorbent assay. The data were analysed by bivariate tests and multivariate analysis of variance (5% level). Salivary cortisol levels were lower in the MS group than in the PS group at the time of anaesthesia (p = 0.004), but did not vary during the appointment within sedation (p = 0.319) or placebo (p = 0.080) groups. Children's behaviour was negative most of the time and did not differ between MS and PS; however, the behaviour (OSUBRS) did not correlate with salivary cortisol levels. Oral midazolam is able to control salivary cortisol levels during dental treatment of pre-schoolers, which might not lead to better clinical behaviour. PMID- 26892360 TI - Validation of micro-computed tomography for occlusal caries detection: an in vitro study. AB - Conventional methods of caries detection, including the gold standard of histological examination, have certain disadvantages that must be addressed prior to validating any other diagnostic technique-current or new. Here we evaluated the validity of micro-computed tomography (micro-CT) as an alternative gold standard technique for caries detection. Sixty teeth with suspected occlusal caries were chosen from a pool of teeth extracted for orthodontic, periodontal, or surgical reasons. Identical reference points were marked on photographs taken for teeth and were used to evaluate each method. Dimensions of caries were assessed by two calibrated examiners using the ICDAS-II visual examination system, bitewing radiographs, and micro-CT. The teeth included in the study were selected randomly from solution before all measurements. For micro-CT, the device was set to 50 kV, 800 uA, pixel size 15 um (at 1024 * 1024 resolution), and 1 degrees rotation step. NRecon software (SkyScan) was used to obtain reconstructed images. For each diagnostic method, results were compared with histology results using the McNemar test. Receiver operator characteristic (ROC) analysis was also performed for each method (Z-test; p < 0.05). Besides showing a high correlation with histology results, micro-CT yielded the greatest values at the D3 threshold; moreover, accuracy and area under the ROC curve (AUC) values were greatest at the D1threshold. Our results indicate that micro-CT performs as well as or better than histological examination for the purpose of comparing methods for caries detection. PMID- 26892361 TI - Caries-risk profiles in Italian adults using computer caries assessment system and ICDAS. AB - The aim of this study was to examine the correlation among socio-behavioral factors, caries status and caries risk, calculated through Cariogram, in an adult population. Four hundred eighty subjects (mean age 40.73, SE +/- 0.33) randomly selected from the municipal electoral registry consented to participate in the survey. Subjects were examined, and the International Caries Detection Assessment System (ICDAS) index was registered. A highly structured questionnaire was submitted to investigate (1) personal data (i.e., age, gender, educational level, job categorization), (2) life-style behavior (i.e., smoking and dietary habits), and (3) oral health behavior (i.e., tooth brushing, use of fluoride and dental check-up frequency). An evaluation of the mutans streptococci concentration in saliva was also performed. Information on caries-related factors was entered into the Cariogram in order to generate an individual caries risk profile for each subject. Multinomial logistic regression was performed using Cariogram levels as the dependent variable. The possible correlated variables were analyzed using the principal component analysis (PCA). Considering ICDAS scores, 5.62% of the sample had at least an initial decay (ICDAS = 1-2), whereas 40.83% of the sample presented at least one moderate decay (ICDAS = 3-4) and 17.08% a severe decay (ICDAS = 5-6). Decay at ICDAS levels 5-6 and more than 5 missing teeth were statistically associated with Cariogram scores (OR = 2.36, 95%CI = 1.83-3.03 and OR = 1.43, 95%CI = 1.13-1.82, respectively). The results suggest that the Cariogram model was able to identify caries-related factors in an adult population. A direct association among the risk categories from Cariogram, the caries status and some socio-behavioral variables was verified. PMID- 26892363 TI - Corrigendum. PMID- 26892364 TI - Cuspal Deflection of Premolars Restored with Bulk-Fill Composite Resins. AB - OBJECTIVE: This in vitro study compared cuspal deflection of premolars restored with three bulk-fill composite resins to that of incrementally-restored ones with a low-shrinkage silorane-based restorative material. MATERIALS AND METHODS: Forty freshly-extracted intact human upper premolars were used. Reference points at buccal and palatal cusp tips were acid-etched and composite rods were horizontally bonded to them (TPH-Spectra-HV, Dentsply). Two acrylic resin guiding paths were made for each premolar to guide beaks of a digital micrometer used for cuspal deflection measurements. Standardized MOD cavities, 3 mm wide bucco lingually and 3.5 mm deep, were prepared on each premolar. Prepared teeth were then equally divided into four groups (n = 10) and each group was assigned to one of four composite resin (QuiXX, Dentsply; X-tra fil, Voco; Tetric EvoCeram Bulk Fill, Ivoclar Vivadent; low-shrinkage Filtek LS, 3M/ESPE). Adper Single Bond Plus, 3M/ESPE was used with all bulk-fill restoratives. LS-System Adhesive, 3M/ESPE was used with Filtek LS. For each prepared premolar, cuspal deflection was measured in microns as the difference between two readings between reference points before and after restoration completion. Means and SDs were calculated and data statistically-analyzed using One-way ANOVA and Tukey's test. RESULTS: Filtek LS showed the lowest mean cuspal deflection value 6.4(0.84)MUm followed by Tetric EvoCeram Bulk Fill 10.1(1.2) MUm and X-tra fil 12.4(1.35)MUm, while QuiXX showed the highest mean 13(1.05)MUm. ANOVA indicated significant difference among mean values of groups (p < 0.001). Tukey's test indicated no significant difference in mean values between QuiXX and X-tra fil (p = 0.637). CONCLUSIONS: Tetric EvoCeram Bulk Fill had significantly lower mean cuspal deflection compared with the two other bulk-fill composite resins tested. Filtek LS had the lowest significant mean cuspal deflection in comparison to all tested bulk-fill restoratives. CLINICAL SIGNIFICANCE: The use of Tetric EvoCeram Bulk fill composite resin restorative for class II MOD cavities resulted in reduced cuspal deflection in comparison to the two other bulk-fill composite resins tested. The silorane-based Filtek LS restorative resulted in the least cuspal deflection in comparison to all tested bulk-fill composite restoratives. PMID- 26892362 TI - Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner. AB - Progranulin (PGRN), a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host-defense. PGRN also has potent anti-inflammatory functionality, and deregulated PGRN is associated with rheumatoid arthritis and inflammatory bowel disease. We have previously reported that PGRN directly binds to TNFR and significantly enhances Treg population and stimulates IL-10 production. To further investigate PGRN's function in the immune system we performed a gene array analysis on CD4+ T cells from wild type B6 mice and PGRN -/- mice. We identified many chemokines and their receptors, among which CXCL9 and CXCL10 were most prominent, that were significantly induced in PGRN null mice. Administration of recombinant PGRN protein strongly inhibited TNF and IFN-gamma-induced CXCL9 and CXCL10 expression. In addition, CXCL9 expression is strongly upregulated in PGRN KO mice and its level is correlated with severity of inflammation in a dermatitis model. Further, we have demonstrated that PGRN mediated inhibition of chemokine expression largely depends on TNFR1. Taken together, this study provides new insights into the mechanisms underlying PGRN mediated regulation of various inflammatory and autoimmune diseases. PMID- 26892365 TI - Extracorporeal photopheresis in solid organ transplant-associated acute graft versus-host disease. AB - BACKGROUND: Extracorporeal photopheresis (ECP) culls pathogenic T lymphocytes, be these the clones of cutaneous T-cell lymphoma, or mediators of chronic graft versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT GVHD). Whether or not ECP may have an effect in the rarer instances of solid organ transplantation-associated GVHD (SOT-GVHD) is unclear. Mortality rates in SOT-GVHD rival those of transfusion-associated GVHD, with fatalities preceded by pancytopenia and peripheral blood chimerism (PBC) levels exceeding 20%. ECP has been described in two SOT-GVHD cases to date, with one surviving. STUDY DESIGN AND METHODS: Clinicolaboratory features (including HLA relationships) in a case of multivisceral transplantation were reviewed from the time of surgery to the onset and progression of SOT-GVHD. ECP, which was introduced as a less immunosuppressive and more selective intervention, was assessed for its effect on serial PBC (as measured by short-tandem-repeat analysis) and clinical outcome. RESULTS: Multivisceral SOT-GVHD manifested with erythroderma, neutropenic sepsis, and PBC increasing from 6% on Posttransplant Day (PTD) 38 to 78% by PTD 60 (at a doubling time of 6 days despite corticosteroids). ECP was administered on PTDs 62 and 67 and was associated with the first evidence of PBC decay to 67% on PTD 69. Death nevertheless ensued on the last day of salvage antithymocyte globulin (PTDs 69-73) despite further PBC reduction to 41%. CONCLUSION: Further study is needed to determine if the sooner or more frequent application of ECP might attenuate the high case fatality rates of SOT-GVHD. PMID- 26892366 TI - Synthesis of Highly Crystalline Multilayered Boron Niride Microflakes. AB - Boron niride microflakes of 2-5 MUm in diameter and greater than 40 MUm in length with multilayer structure and highly crystalline nature are synthesized in two states of catalysts and dual role of nitrogen at 1100 degrees C. Most of the microflakes are flat, smooth and vertically aligned with a wall-like view from the top. Transmission electron microscopy shows overlapped layers of microflakes with an interlayer spacing of 0.34 nm. The h-BN components of the synthesized microflakes are verified from B 1s and N1 s peaks at 190. 7 and 397.9 eV. Raman shift at 1370 (cm(-1)) and sharp peaks in the XRD pattern further confirm the h BN phase and crystalline nature of the synthesized microflakes. Microflakes of h BN with the above characteristics are highly desirable for the development of a solid state neutron detector with higher detection efficiency. PMID- 26892367 TI - Authors' reply: Comment on: Monitoring treatment practices of childhood asthma in singapore: a questionnaire study. PMID- 26892370 TI - Magnetic resonance imaging findings in spinal hemangioblastoma case. PMID- 26892369 TI - Cellulose-Based Biosensors for Esterase Detection. AB - Cellulose has emerged as an attractive substrate for the production of economical, disposable, point-of-care (POC) analytical devices. Development of novel methods of (bio)activation is central to broadening the application space of cellulosic materials. Ironically, such efforts are stymied by the inherent biocompatibility and recalcitrance of cellulose fibers. Here, we have elaborated a versatile, chemo-enzymatic approach to activate cellulosic materials for CuAAC "click chemistry", to develop new fluorogenic esterase sensors. Gentle, aqueous modification conditions facilitate broad applicability to cellulose papers, gauzes, and hydrogels. Tethering of the released fluorophore to the cellulose surface prevents signal degradation due to diffusion and enables straightforward, sensitive visualization with a simple light source in resource-limited situations. PMID- 26892368 TI - Expression partitioning of homeologs and tandem duplications contribute to salt tolerance in wheat (Triticum aestivum L.). AB - Salt stress dramatically reduces crop yield and quality, but the molecular mechanisms underlying salt tolerance remain largely unknown. To explore the wheat transcriptional response to salt stress, we performed high-throughput transcriptome sequencing of 10-day old wheat roots under normal condition and 6, 12, 24 and 48 h after salt stress (HASS) in both a salt-tolerant cultivar and salt-sensitive cultivar. The results demonstrated global gene expression reprogramming with 36,804 genes that were up- or down-regulated in wheat roots under at least one stress condition compared with the controls and revealed the specificity and complexity of the functional pathways between the two cultivars. Further analysis showed that substantial expression partitioning of homeologous wheat genes occurs when the plants are subjected to salt stress, accounting for approximately 63.9% (2,537) and 66.1% (2,624) of the homeologous genes in 'Chinese Spring' (CS) and 'Qing Mai 6' (QM). Interestingly, 143 salt-responsive genes have been duplicated and tandemly arrayed on chromosomes during wheat evolution and polyploidization events, and the expression patterns of 122 (122/143, 85.3%) tandem duplications diverged dynamically over the time-course of salinity exposure. In addition, constitutive expression or silencing of target genes in Arabidopsis and wheat further confirmed our high-confidence salt stress responsive candidates. PMID- 26892371 TI - Ischiofemoral impingement syndrome: another cause of extraspinal sciatica. PMID- 26892373 TI - Tuberculosis of the spine. PMID- 26892372 TI - Congenital cervicothoracic spondyloptosis in a 7-month-old patient. PMID- 26892374 TI - Gunshot wound causing anterior spinal cord infarction due to injury to the artery of Adamkiewicz. PMID- 26892375 TI - Postpartum sacral insufficiency fracture. PMID- 26892376 TI - Hyperresistinemia and metabolic dysregulation: a risky crosstalk in obese breast cancer. AB - Breast cancer is the most common malignancy among women worldwide. There is extensive literature on the relationship between body weight and breast cancer risk but some doubts still remain about the role of adipokines per se, the role of insulin and glucose regardless of obesity, as well as the crosstalk between these players. Thus, in this study, we intend to determine the relation between body mass index (BMI), glycaemia, insulinemia, insulin-resistance, blood adipokine levels and tumour characteristics in a Portuguese group of pre- and postmenopausal overweight/obese women with breast cancer. We evaluated clinical and biochemical data in 154 participants, divided in 4 groups: (1) control with BMI <25 kg/m(2), n = 29 (CT); (2) control with BMI >25 kg/m(2), n = 48 (CTOb); (3) breast cancer with BMI <25 kg/m(2), n = 30 (BC); and (4) breast cancer with BMI >25 kg/m(2), n = 47 (BCOb). In women with breast cancer, we also performed tumour characterization. We found that BCOb present increased fasting blood glucose, insulin, resistin and monocyte chemoattractant protein 1, insulin resistance and more aggressive tumours. Notably, this profile is not correlated with BMI, proposing the involvement of other processes than adiposity. Altogether, our results suggest that glucose dysmetabolism, insulin resistance and changes in adipokine secretion, in particular resistin, may be involved in the development and progression of breast cancer in overweight/obese pre- and postmenopausal women. PMID- 26892378 TI - Parotid gland lesions: separate and combined diagnostic value of conventional MRI, diffusion-weighted imaging and dynamic contrast-enhanced MRI. AB - OBJECTIVE: To evaluate the ability of conventional MRI, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) MRI to differentiate malignant and benign parotid lesions. METHODS: A retrospective review of MRI findings was performed in patients with pathologically confirmed parotid lesions between January 2010 and December 2014. Morphological MRI characteristics and functional characteristics such as apparent diffusion coefficient (ADC) and pattern of time signal intensity curve (TIC) were recorded and compared. For each lesion, summed scores were respectively calculated for conventional MRI alone, conventional MRI with DWI and/or with DCE-MRI. Statistical analyses were performed to assess the association of these characteristics and summed scores with malignancy. RESULTS: A total of 207 patients (111 males and 96 females; age: 48.4 +/- 17.0 years) were included, consisting of 156 benign and 51 malignant tumours. After adjusting for age, sex, smoking status, alcohol use and tumour size, the lesions with ill defined margin, adjacent tissue infiltration, cervical lymphadenopathy, ADC <=1.01 * 10(-3) mm(2) s(-1) and plateau TIC pattern are more likely to be malignant than those without these findings. Significant difference in receiver operator characteristic was detected after adding DWI to conventional MRI (p = 0.003), generating a sensitivity and specificity of 54.05% and 91.30%, respectively. Compared with lesions score <3, lesions with score >=5 in the combination of conventional MRI and DWI were approximately 90 times more likely to be malignant parotid tumour. Additional DCE-MRI did not improve differential ability of conventional MRI. CONCLUSION: Morphological and functional MRI characteristics are associated with malignancy in parotid gland. The diagnostic value of MRI would increase when DWI is applied in combination with conventional MRI. ADVANCES IN KNOWLEDGE: The parotid lesions with ill-defined margin, adjacent tissue infiltration, cervical lymphadenopathy, ADC <=1.01 * 10(-3) mm(2) s(-1) and plateau TIC pattern are more likely to be malignant. The diagnostic value of conventional MRI would be increased when DWI is applied in combination, whereas additional DCE-MRI did not improve differential ability of conventional MRI. PMID- 26892377 TI - From disease to treatment: from rare skeletal disorders to treatments for osteoporosis. AB - During the past 15 years there has been an expansion of our knowledge of the cellular and molecular mechanisms regulating bone remodeling that identified new signaling pathways fundamental for bone renewal as well as previously unknown interactions between bone cells. Central for these developments have been studies of rare bone disorders. These findings, in turn, have led to new treatment paradigms for osteoporosis some of which are at late stages of clinical development. In this article, we review three rare skeletal disorders with case descriptions, pycnodysostosis and the craniotubular hyperostoses sclerosteosis and van Buchem disease that led to the development of cathepsin K and sclerostin inhibitors, respectively, for the treatment of osteoporosis. PMID- 26892381 TI - Dermoscopy of Grover's disease: Variability according to histological subtype. AB - Distinguishing Grover's disease from other papular dermatoses is often a troublesome task. According to two relatively recent case reports, dermoscopy may be useful in assisting the diagnosis of such a disorder by showing a peculiar pattern. The aim of this study was to evaluate the dermoscopic features of Grover's disease in a larger series of patients and correlate dermoscopy with histopathological findings. Seven patients with histopathologically confirmed Grover's disease were included in the study, with three of them displaying a Darier-like histology and the remaining four cases having a spongiotic histological pattern. The results of our study suggest that Grover's disease may display different features according to the histological subtype, with a central star-shaped/branched polygonal/roundish-oval brownish area surrounded by a whitish halo being characteristic of the Darier-like histological subtype and whitish scales over a reddish-yellowish background being characteristic of the spongiotic histological subtype. PMID- 26892379 TI - Nicotinic effects of tobacco smoke constituents in nonhuman primates. AB - RATIONALE: Recent studies in rodents suggest that non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may promote tobacco consumption either through their own pharmacological effects or by augmenting the effects of nicotine. However, there is scant information on the behavioral pharmacology of minor tobacco alkaloids in primate species. OBJECTIVE: The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine, anabasine, anatabine, myosmine, and cotinine exhibit nicotine-like behavioral effects in squirrel monkeys. METHODS: Initial experiments were conducted to determine the effects of nicotine (0.032-1.0 mg/kg) and the minor tobacco alkaloids nornicotine (1-1.8 mg/kg), anabasine (0.1-1.0 mg/kg), anatabine (10-32 mg/kg), myosmine (0.32-1.8 mg/kg), and cotinine (10-180 mg/kg) on food-maintained performance (n = 4). Next, the ability of tobacco alkaloids to substitute for the alpha4beta2-selective nicotinic agonist (+)-epibatidine in drug discrimination experiments was evaluated in a separate group of monkeys (n = 4). RESULTS: Results show that nicotine and each minor tobacco alkaloid except cotinine (a) produced dose-related decreases in food-maintained responding; (b) substituted for (+)-epibatidine and, in additional experiments, produced additive effects when combined with nicotine; (c) induced emesis or tremor at doses that reduced food-maintained responding and had (+)-epibatidine-like discriminative-stimulus effects; and (d) based on correlation with reported receptor binding affinities, likely produced their behavioral effects through alpha4beta2 receptor mechanisms. CONCLUSION: Selected minor tobacco alkaloids have nicotinic-like effects that may contribute to tobacco consumption and addiction. PMID- 26892383 TI - Multiple contrast type tests for the evaluation of animal carcinogenicity studies. AB - The Cochran-Armitage (CA) test is frequently used for testing the dose-response relationship in tumor incidence. This test is based on a weighted linear regression of proportions. It is well known that the CA test lacks power for nonlinear tumor outcomes. For general shape of outcomes, Hothorn and Bretz (2000) proposed a multiple contrast (MC) test. This test suggests the use of the maximum over several single contrasts, where each of them is chosen appropriately to cover a specific dose-response shape. In this work, two new test procedures are proposed and they are compared to the CA and MC tests using power. PMID- 26892380 TI - Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. AB - RATIONALE: Hypofunction of striatal dopamine neurotransmission, or hypodopaminergia, is a consequence of excessive ethanol use and is hypothesized to be a critical component of alcoholism, driving alcohol intake in an attempt to restore dopamine levels; however, the neurochemical mechanisms involved in these dopaminergic deficiencies are not fully understood. OBJECTIVE: Here we examined the specific dopaminergic adaptations that produce hypodopaminergia and contribute to alcohol use disorders using direct, sub-second measurements of dopamine signaling in nonhuman primates following chronic ethanol self administration. METHODS: Female rhesus macaques completed 1 year of daily (22 h/day) ethanol self-administration. Subsequently, fast-scan cyclic voltammetry was used in nucleus accumbens core brain slices to determine alterations in dopamine terminal function, including release and uptake kinetics, and sensitivity to quinpirole (D2/D3 dopamine receptor agonist) and U50,488 (kappa opioid receptor agonist) induced inhibition of dopamine release. RESULTS: Ethanol drinking greatly increased uptake rates, which were positively correlated with lifetime ethanol intake. Furthermore, the sensitivity of dopamine D2/D3 autoreceptors and kappa opioid receptors, which both act as negative regulators of presynaptic dopamine release, was moderately and robustly enhanced in ethanol drinkers. CONCLUSIONS: Greater uptake rates and sensitivity to D2-type autoreceptor and kappa opioid receptor agonists could converge to drive a hypodopaminergic state, characterized by reduced basal dopamine and an inability to mount appropriate dopaminergic responses to salient stimuli. Together, we outline the specific alterations to dopamine signaling that may drive ethanol induced hypofunction of the dopamine system and suggest that the dopamine and dynorphin/kappa opioid receptor systems may be efficacious pharmacotherapeutic targets in the treatment of alcohol use disorders. PMID- 26892382 TI - Circulation of HIV-1 Multiple Complexity Recombinant Forms Among Female Sex Workers Recently Infected with HIV-1 in Thailand. AB - The circulating subtype distribution of HIV-1 has not been well characterized in female sex worker (FSW) populations in Thailand. To understand the mechanisms and interrelationships of epidemics involving FSWs in Thailand, we performed a large molecular epidemiological study of FSWs aged 25 years with recently acquired HIV 1 infections. The samples were collected in 2005, 2007, 2009, and 2011 in 38 provinces, representing every region of Thailand. After gag (p24), pol (pro-RT), and env (C2/V3) were sequenced, comprehensive genome analysis was performed. Genetic subtypes were determined in 159 plasma samples. The percentage of circulating recombinant forms (CRFs) CRF01_AE (90.6%) predominated, while subtype B (1.3%), other CRFs (1.9%), and unique recombinant forms (URFs) (6.2%) were identified as minor populations. Interestingly, the unique recombinant nature of these HIV-1 strains was verified in 10 specimens, indicating the presence of new forms of HIV-1 intersubtypes G/A, C/B, AE/B/C, and AE/B with different recombination breakpoints. Subtype B has contributed to these new generations of unique CRF01/B recombinants, especially in the pol (RT) gene, in which the template switching of the RT genomes occurred during reverse transcription. These results imply that the several unique recombinant viruses circulating in Thailand were probably generated in the population or introduced from neighboring countries. Our study helps clarify the patterns of viral transmission and define transmission pathways in Thailand. PMID- 26892384 TI - Passive trapping of rigid rods due to conformation-dependent electrophoretic mobility. AB - We present computer simulations of a rigid rod in a combination of an extensional fluid flow and extensional electric field. The electrophoretic mobility of the rod is different parallel or perpendicular to the rod. The dependence of the mobility on the conformation (orientation) leads to a new phenomenon where the rods can be passively trapped in all directions at the stagnation point. This contrasts with the behavior in either fluid flow or electric field alone, in which an object can be pushed towards the stagnation point along some directions but is pushed away in others. We have determined the state space where trapping occurs and have developed a model that describes the strength of trapping when it does occur. This new phenomenon could be used in the future to separate objects based on a coupling between their mobility and ability to be oriented. PMID- 26892385 TI - Structural and electronic features of binary Li2S-P2S5 glasses. AB - The atomic and electronic structures of binary Li2S-P2S5 glasses used as solid electrolytes are modeled by a combination of density functional theory (DFT) and reverse Monte Carlo (RMC) simulation using synchrotron X-ray diffraction, neutron diffraction, and Raman spectroscopy data. The ratio of PSx polyhedral anions based on the Raman spectroscopic results is reflected in the glassy structures of the 67Li2S-33P2S5, 70Li2S-30P2S5, and 75Li2S-25P2S5 glasses, and the plausible structures represent the lithium ion distributions around them. It is found that the edge sharing between PSx and LiSy polyhedra increases at a high Li2S content, and the free volume around PSx polyhedra decreases. It is conjectured that Li(+) ions around the face of PSx polyhedra are clearly affected by the polarization of anions. The electronic structure of the DFT/RMC model suggests that the electron transfer between the P ion and the bridging sulfur (BS) ion weakens the positive charge of the P ion in the P2S7 anions. The P2S7 anions of the weak electrostatic repulsion would causes it to more strongly attract Li(+) ions than the PS4 and P2S6 anions, and suppress the lithium ionic conduction. Thus, the control of the edge sharing between PSx and LiSy polyhedra without the electron transfer between the P ion and the BS ion is expected to facilitate lithium ionic conduction in the above solid electrolytes. PMID- 26892386 TI - A multi-parametric assessment of decontamination protocols for the subglacial Lake Ellsworth probe. AB - Direct measurement and sampling of pristine environments, such as subglacial lakes, without introducing contaminating microorganisms and biomolecules from the surface, represents a significant engineering and microbiological challenge. In this study, we compare methods for decontamination of titanium grade 5 surfaces, the material extensively used to construct a custom-made probe for reaching, measuring and sampling subglacial Lake Ellsworth in West Antarctica. Coupons of titanium were artificially contaminated with Pseudomonas fluorescens bacteria and then exposed to a number of decontamination procedures. The most effective sterilants were (i) hydrogen peroxide vapour, and (ii) BiocleanseTM, a commercially available, detergent-based biocidal solution. After each decontamination procedure the bacteria were incapable of proliferation, and showed no evidence of metabolic activity based on the generation of adenosine triphosphate (ATP). The use of ultraviolet irradiation or ethyl alcohol solution was comparatively ineffective for sterilisation. Hydrogen peroxide vapour and ultraviolet irradiation, which directly damage nucleic acids, were the most effective methods for removing detectable DNA, which was measured using 16S rRNA gene copy number and fluorescence-based total DNA quantification. Our results have not only been used to tailor the Ellsworth probe decontamination process, but also hold value for subsequent engineering projects, where high standards of decontamination are required. PMID- 26892388 TI - Role of skeletal muscle in motor neuron development. AB - The current paper is a continuation of our work most recently described in Kablar, 2011. Here, we show lists of up- and down-regulated genes obtained by a cDNA microarray analysis that compared developing mouse MyoD-/- limb musculature (MyoD-dependent, innervated by Lateral Motor Column motor neurons) and Myf5-/- back (epaxial) musculature (Myf5-dependent, innervated by Medial Motor Column motor neurons) to the control and to each other, at embryonic day 13.5 which coincides with the robust programmed cell death of motor neurons and the inability of myogenesis to undergo its normal progression in the absence of Myf5 and MyoD that at this embryonic day cannot substitute for each other. We wanted to see if/how the myogenic program couples with the neurotrophic one, and also to separate Lateral from Medial column trophic requirements, potentially relevant to Motor Neuron Diseases with the predilection for the Lateral column. Several follow-up steps revealed that Kif5c, Stxbp1 and Polb, differentially expressed in the MyoD-/- limb muscle, and Ppargc1a, Glrb and Hoxd10, differentially expressed in the Myf5-/- back muscle, are actually regulators of motor neuron numbers. We propose a series of follow-up experiments and various ways to consider our current data. PMID- 26892387 TI - Acute ecotoxicology of natural oil and gas condensate to coral reef larvae. AB - Risks posed by oil spills to coral reefs are difficult to evaluate, partially due to the absence of studies that adequately assess toxicity to relevant coral reef species. Here we experimentally tested the acute toxicity of condensate, representing a fraction of light crude oil, to coral (Acropora tenuis) and sponge (Rhopaloeides odorabile) larvae. The metamorphosis of coral larvae was inhibited at total petroleum aromatic hydrocarbon (TPAH) concentrations of water accommodated fractions (WAF) as low as 103 MUg l(-1), similar to concentrations detected in seawater following large spills. The sensitivity of coral larvae increased by 40% when co-exposed to UV light that they might encounter in shallow reefal systems. Condensate WAF was more toxic to coral larvae than predicted by summing the toxicity of its main components (benzene, toluene, p-xylene and napthalene). In contrast, the sensitivity of sponge larvae to condensate WAF (>10,000 MUg l(-1) TPAH) was far less than coral in the presence and absence of UV, but similar to that of other marine invertebrates. While these results highlight the relative sensitivity of coral larvae to oil, further research is needed to better understand and predict the impacts and risks posed by hydrocarbons to tropical reef systems. PMID- 26892389 TI - Lung-gut cross-talk: evidence, mechanisms and implications for the mucosal inflammatory diseases. AB - The mucosal immune system (including airway, intestinal, oral and cervical epithelium) is an integrated network of tissues, cells and effector molecules that protect the host from environmental insults and infections at mucous membrane surfaces. Dysregulation of immunity at mucosal surfaces is thought to be responsible for the alarming global increase in mucosal inflammatory diseases such as those affecting the gastrointestinal (Crohn's disease, ulcerative colitis and irritable bowel syndrome) and respiratory (asthma, allergy and chronic obstructive pulmonary disorder) system. Although immune regulation has been well studied in isolated mucosal sites, the extent of the immune interaction between anatomically distant mucosal sites has been mostly circumstantial and the focus of much debate. With novel technology and more precise tools to examine histological and functional changes in tissues, today there is increased appreciation of the 'common mucosal immunological system' originally proposed by Bienenstock nearly 40 years ago. Evidence is amounting which shows that stimulation of one mucosal compartment can directly and significantly impact distant mucosal site, however the mechanisms are unknown. Today, we are only beginning to understand the complexity of relationships and communications that exist between different mucosal compartments. A holistic approach to studying the mucosal immune system as an integrated global organ is imperative for future advances in understanding mucosal immunology and for future treatment of chronic diseases. In this review, we particularly focus on the latest evidence and the mechanisms operational in driving the lung-gut cross-talk. PMID- 26892390 TI - Living through a volcanic eruption: Understanding the experience of survivors as a phenomenological existential phenomenon. AB - Mount Merapi in Indonesia is the most active volcano in the world with its 4-6 year eruption cycle. The mountain and surrounding areas are populated by hundreds of thousands of people who live near the volcano despite the danger posed to their wellbeing. The aim of this study was to explore the lived experience of people who survived the most recent eruption of Mount Merapi, which took place in 2010. Investigators conducted interviews with 20 participants to generate textual data that were coded and themed. Three themes linked to the phenomenological existential experience (temporality and relationality) of living through a volcanic eruption emerged from the data. These themes were: connectivity, disconnection and reconnection. Results indicate that the close relationship individuals have with Mount Merapi and others in their neighbourhood outweighs the risk of living in the shadow of an active volcano. This is the first study to analyze the phenomenological existential elements of living through a volcanic eruption. PMID- 26892391 TI - The photocatalytic properties of ultrathin bismuth oxychloride nanosheets: a first principles study. AB - Two-dimensional (2D) nanosheet structures have obvious advantages with respect to their bulk counterparts in photocatalytic reaction due to their extraordinary electronic and optical properties. So do the 2D BiOCl nanosheets with significant improvement of photocatalytic activity in the degradation of dyes shown by recent studies. In the present work, the surface energies, electronic structure and photocatalytic properties of ultrathin BiOCl nanosheets are examined by means of density functional theory to investigate the origin of their high photocatalytic performance. The results show that the Cl atom terminated BiOCl(001) surface possesses lower surface energy than others and is very likely to be introduced in the ultrathin nanosheet. Moreover, our proposed model accounts well for the origin of band edge upshift of the ultrathin BiOCl nanosheets with respect to BiOCl nanoplates observed in experiments. In addition, the presence of Bi vacancies on the surfaces of nanosheets can enhance the built-in electric field and further promote the separation of photo-generated carriers, which is extremely advantageous for the photocatalytic process. Our results provide a new insight into the high photocatalytic performance of BiOCl(001) nanosheets. PMID- 26892393 TI - Computed Tomography for Coronary Artery Calcification Scoring: Mammogram for the Heart. AB - Coronary artery calcium (CAC), identified via low-radiation, non-contrast computed tomography of the heart, quantifies the burden of calcified coronary atherosclerosis. This modality is highly useful for cardiovascular (CV) risk stratification among individuals without known coronary heart disease (CHD), especially for those at intermediate risk. The presence of CAC is associated with up to a 10-fold higher risk of adverse CV events, even after fully adjusting for the standard CV risk factors. In fact, the CAC score is among the strongest clinically available predictors of future risk of adverse CV events among primary prevention patients. Additionally, the absence of CAC in asymptomatic individuals confers a very low risk of CV events. Even in the presence of a benign CV risk factor profile and normal cardiac stress test, a very high CAC score portends a high risk of adverse CV events. On the other hand, a CAC score of zero is associated with a low CHD risk despite significant CV risk factor profiles. CAC scoring is a quick, low-cost screening tool to help risk-stratify patients and identify those likely to benefit from aggressive preventive treatments (such as high-intensity statin therapy, ezetimibe, PCSK9 inhibitors, and aspirin) and to identify those likely who warrant close monitoring. Moreover, individuals with a zero CAC score may be at low enough risk to avoid or defer daily aspirin therapy and pharmacological therapy for cholesterol management, and instead work on therapeutic lifestyle changes. An abnormal CAC score may also lead to better adherence to pharmacological regimens and suggested lifestyle changes. PMID- 26892392 TI - Discovering gene re-ranking efficiency and conserved gene-gene relationships derived from gene co-expression network analysis on breast cancer data. AB - Systemic approaches are essential in the discovery of disease-specific genes, offering a different perspective and new tools on the analysis of several types of molecular relationships, such as gene co-expression or protein-protein interactions. However, due to lack of experimental information, this analysis is not fully applicable. The aim of this study is to reveal the multi-potent contribution of statistical network inference methods in highlighting significant genes and interactions. We have investigated the ability of statistical co expression networks to highlight and prioritize genes for breast cancer subtypes and stages in terms of: (i) classification efficiency, (ii) gene network pattern conservation, (iii) indication of involved molecular mechanisms and (iv) systems level momentum to drug repurposing pipelines. We have found that statistical network inference methods are advantageous in gene prioritization, are capable to contribute to meaningful network signature discovery, give insights regarding the disease-related mechanisms and boost drug discovery pipelines from a systems point of view. PMID- 26892394 TI - MyoD Overexpressed Equine Adipose-Derived Stem Cells Enhanced Myogenic Differentiation Potential. AB - Mesenchymal stem cells could potentially be used in the clinical treatment of muscle disorders and muscle regeneration. Adipose-derived stem cells (ADSCs) can be easily isolated from adipose tissue, as opposed to stem cells of other tissues. We believe that cell therapy using ADSCs could be applied to muscle disorders in horses and other species. We sought to improve the myogenic differentiation potential of equine ADSCs (eqADSCs) using a MyoD lentiviral vector. MyoD lentiviruses were transduced into eqADSCs and selected using puromycin. Cells were cultured in differentiation media containing 5% horse serum, and after 5 days the MyoD-transduced cells differentiated into myogenic cells (MyoD-eqADSCs). Using green fluorescent protein (GFP), MyoD-eqADSCs were purified and transplanted into the tibialis anterior muscles of mice after they were injured with the myotoxin notexin. The mice were sacrificed to examine any regeneration in the tibialis anterior muscle 4 weeks after the MyoD-eqADSCs were injected. The MyoD-eqADSCs cultured in growth media expressed murine and equine MyoD; however, they did not express late differentiation markers such as myogenin (MYOG). When cells were grown in differentiation media, the expression of MYOG was clearly observed. According to our reverse transcription polymerase chain reaction and immunocytochemistry results, MyoD-eqADSCs expressed terminal myogenic phase genes, such as those encoding dystrophin, myosin heavy chain, and troponin I. The MyoD-eqADSCs fused to each other, and the formation of myotube like cells from myoblasts in differentiation media occurred between days 5 and 14 postplating. In mice, we observed GFP-positive myofibers, which had differentiated from the injected MyoD-eqADSCs. Our approaches improved the myogenic differentiation of eqADSCs through the forced expression of murine MyoD. Our findings suggest that limitations in the treatment of equine muscle disorders could be overcome using ADSCs. PMID- 26892395 TI - Sleep-disordered breathing and daytime postural stability. AB - OBJECTIVE: Postural stability depends on the coordination of the central nervous system with visual sense, proprioceptive and vestibular information. Sleep deprivation has been shown to affect this function. The objective of our study was to assess the effects of sleep-disordered breathing (SDB) on postural stability. METHODS: 158 subjects referred for suspected SDB had an overnight sleep study and were placed on a posturographic platform in late afternoon. This platform allows measuring the centre of pressure (CoP) oscillations and to calculate: total displacement of CoP in X and Y axes, mean speed of CoP displacement and the length as function of surface (LFS) ratio (length of CoP displacement/surface of CoP trajectory). RESULTS: 98 men and 60 women were included. Mean age+/-SD was 45.4+/-5.5 years old, body mass index (BMI) 27.5+/ 5.6 kg/m(2) and apnoea-hypopnoea index (AHI) 13.6+/-16.1/h. AHI was <5/h in 64 (41%) subjects, 5-15/h in 43 (27%), 15-30/h in 30 (19%) and >30/h in 21 (13%). In patients with an AHI >5/h versus AHI <5/h, we observed an important increase in LFS (+21%, p<0.001), in XY length (+23%, p<0.001) and in mean speed (+23%, p<0.001). After controlling for age, BMI and sleepiness (Epworth) in multivariate regression models, there was a positive association between all nocturnal breathing parameters (specifically: mean SpO2, AHI, oxygen desaturation index 3% and % time with SpO2 <90%) and the main stability outcomes (all p<0.05). CONCLUSIONS: SDB severity, especially the mean nocturnal SpO2 level, is associated with impaired daytime postural stability. PMID- 26892397 TI - Involvement of Transient Receptor Potential Cation Channel Vanilloid 1 (TRPV1) in Myoblast Fusion. AB - The mechanisms that underlie the complex process of muscle regeneration after injury remain unknown. Transient receptor potential cation channel vanilloid 1 (TRPV1) is expressed in several cell types, including skeletal muscle, and is activated by high temperature and by certain molecules secreted during tissue inflammation. Severe inflammation and local temperature perturbations are induced during muscle regeneration, which suggests that TRPV1 might be activated and involved in the process. The aim of this study, was to clarify the role of TRPV1 in the myogenic potential of satellite cells responsible for muscle regeneration. We found that mRNA and protein levels of TRPV1 increased during regeneration after cardiotoxin (CTX)-induced muscle injury in mice. Using isolated mouse satellite cells (i.e., myoblasts), we observed that activation of TRPV1 by its agonist capsaicin (CAP) augmented myogenin protein levels. Whereas CAP did not alter myoblast proliferation, it facilitated myoblast fusion (evaluated using myonucleii number per myotube and fusion index). In contrast, suppression of TRPV1 by siRNA impaired myoblast fusion. Using mice, we also demonstrated that intramuscular injection of CAP facilitated muscle repair after CTX-induced muscle injury. Moreover, we showed that these roles of TRPV1 might be mediated by interleukin-4 and calcium signaling during myoblast fusion. Collectively, these results suggest that TRPV1 underlies normal myogenesis through promotion of myoblast fusion. J. Cell. Physiol. 231: 2275-2285, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26892396 TI - Remission of depression following electroconvulsive therapy (ECT) is associated with higher levels of brain-derived neurotrophic factor (BDNF). AB - INTRODUCTION: Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels. METHODS: Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions. RESULTS: Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission * time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald chi(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16). CONCLUSION: ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge. PMID- 26892400 TI - The Significance of Retropharyngeal Nodes in Treatment Deintensification. PMID- 26892398 TI - Investigating tumor perfusion by hyperpolarized 13 C MRI with comparison to conventional gadolinium contrast-enhanced MRI and pathology in orthotopic human GBM xenografts. AB - PURPOSE: Dissolution dynamic nuclear polarization (DNP) enables the acquisition of 13 C magnetic resonance data with a high sensitivity. Recently, metabolically inactive hyperpolarized 13 C-labeled compounds have shown to be potentially useful for perfusion imaging. The purpose of this study was to validate hyperpolarized perfusion imaging methods by comparing with conventional gadolinium (Gd)-based perfusion MRI techniques and pathology. METHODS: Dynamic 13 C data using metabolically inactive hyperpolarized bis-1,1-(hydroxymethyl)-[1-13 C]cyclopropane-d8 (HMCP) were obtained from an orthotopic human glioblastoma (GBM) model for the characterization of tumor perfusion and compared with standard Gd-based dynamic susceptibility contrast (DSC) MRI data and immunohistochemical analysis from resected brains. RESULTS: Distinct HMCP perfusion characteristics were observed within the GBM tumors compared with contralateral normal brain tissue. The perfusion parameters obtained from the hyperpolarized HMCP data in tumor were strongly correlated with normalized peak height measured from the DSC images. The results from immunohistochemical analysis supported these findings by showing a high level of vascular staining for tumor that exhibited high levels of hyperpolarized HMCP signal. CONCLUSION: The results from this study have demonstrated that hyperpolarized HMCP data can be used as an indicator of tumor perfusion in an orthotopic xenograft model for GBM. Magn Reson Med 77:841-847, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26892399 TI - Consumption of echium oil increases EPA and DPA in blood fractions more efficiently compared to linseed oil in humans. AB - BACKGROUND: A plant-based strategy to improve long-chain (LC) omega (n)-3 PUFA supply in humans involves dietary supplementation with oils containing alpha linolenic acid (ALA) alone or in combination with stearidonic acid (SDA). The study aimed to compare the effects of echium oil (EO) and linseed oil (LO) on LC n-3 PUFA accumulation in blood and on clinical markers. METHODS: In two double blind, parallel-arm, randomized controlled studies, all volunteers started with 17 g/d run-in oil (2 weeks). Thereafter, subjects received diets enriched in study 1 with EO (5 g ALA + 2 g SDA; n = 59) or in study 2 with LO (5 g ALA; n = 9) daily for 8 weeks. The smaller control groups received fish oil (FO; n = 19) or olive oil (OO; n = 18). Participants were instructed to restrict their dietary n-3 PUFA intake throughout the studies (e.g., no fish). To investigate the influence of age and BMI on the conversion of ALA and SDA as well as clinical markers, the subjects recruited for EO and LO treatment were divided into three subgroups (two age groups 20-35 y; 49-69 y with BMI 18-25 kg/m(2) and one group with older, overweight subjects (age 49-69 y; BMI >25 kg/m(2)). RESULTS: In plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC), EPA and docosapentaenoic acid (DPA) were ~25 % higher following EO compared to LO. Comparing all treatments, the effectiveness of increasing EPA and DPA in plasma, RBC, and PBMC was on average 100:25:10:0 and 100:50:25:0 for FO:EO:LO:OO, respectively. EO led to a lower arachidonic acid/EPA-ratio compared to LO in plasma, RBC, and PBMC. Following EO, final DHA was not greater compared to LO. Higher BMI correlated negatively with increases in plasma EPA and DPA after EO supplementation, but not after LO supplementation. Decreasing effect on plasma LDL-C and serum insulin was greater with EO than with LO. CONCLUSIONS: Daily intake of SDA-containing EO is a better supplement than LO for increasing EPA and DPA in blood. However, neither EO nor LO maintained blood DHA status in the absence of fish/seafood consumption. TRIAL REGISTRATION: ClinicalTrials.gov Reg No. NCT01856179; ClinicalTrials.gov Reg No. NCT01317290. PMID- 26892402 TI - Robust adaptive backstepping neural networks control for spacecraft rendezvous and docking with input saturation. AB - This paper presents a robust adaptive neural networks control strategy for spacecraft rendezvous and docking with the coupled position and attitude dynamics under input saturation. Backstepping technique is applied to design a relative attitude controller and a relative position controller, respectively. The dynamics uncertainties are approximated by radial basis function neural networks (RBFNNs). A novel switching controller consists of an adaptive neural networks controller dominating in its active region combined with an extra robust controller to avoid invalidation of the RBFNNs destroying stability of the system outside the neural active region. An auxiliary signal is introduced to compensate the input saturation with anti-windup technique, and a command filter is employed to approximate derivative of the virtual control in the backstepping procedure. Globally uniformly ultimately bounded of the relative states is proved via Lyapunov theory. Simulation example demonstrates effectiveness of the proposed control scheme. PMID- 26892403 TI - Morphological models of trabecular bone suitable for high-porosity regions and vertebrae. AB - The complex microarchitecture of trabecular bone makes it difficult to perform computational analyses on the real structure. Researchers have often resorted to using morphological idealizations employing simplified geometries. One such idealized structure, based on the gyroid, was found to mimic trabecular bone well. However, structures generated using the basic gyroid equation manifested discontinuities at high porosities. Another disadvantage of the gyroid is that it cannot model vertebral trabecular bone, which generally resembles cubic cells. To address these two shortcomings, we describe: (i) a modified structure based on the skeletal gyroid, which remains connected even at extremely high porosities, (ii) a cubic grid-like structure, based on the primitive minimal surface, for studying vertebrae. PMID- 26892401 TI - A UHPLC-UV Method to Quantify Skin Deposition and Transdermal Permeation of Tizanidine Hydrochloride. AB - Tizanidine hydrochloride is an alpha2-adrenergic agonist used for the symptomatic relief of spasticity associated with multiple sclerosis or with spinal cord injury or disease. The objective of this study was to develop an isocratic, robust and sensitive ultra-high performance liquid chromatography method using UV detection for use in a project to develop a transdermal therapeutic system to deliver tizanidine across the skin. Isocratic separation was achieved using a C18 column and a mobile phase comprising a 80:20 mixture of 0.004% trifluoroacetic acid in water and MeCN (pH* 3.2) at a flow rate of 0.2 mL min(-1) Tizanidine eluted at 1.499 min and the total run time was 2 min. The method was specific, robust and the response was accurate, precise and linear from 17.4 to 290 ng mL( 1) In contrast to existing methods, the method developed here was validated over a concentration range so as to include the low concentrations frequently observed in transdermal permeation studies and in samples extracted from the cutaneous matrix. Its suitability for use in transdermal permeation studies was subsequently tested and confirmed in preliminary experiments using porcine skin in vitro. PMID- 26892404 TI - In focus in Vienna: the cell nucleus. PMID- 26892405 TI - Social worker assessment of bad news delivery by emergency medicine residents: a novel direct-observation milestone assessment. AB - The skill of delivering bad news is difficult to teach and evaluate. Residents may practice in simulated settings; however, this may not translate to confidence or competence during real experiences. We investigated the acceptability and feasibility of social workers as evaluators of residents' delivery of bad news during patient encounters, and assessed the attitudes of both groups regarding this process. From August 2013 to June 2014, emergency medicine residents completed self-assessments after delivering bad news. Social workers completed evaluations after observing these conversations. The Assessment tools were designed by modifying the global Breaking Bad News Assessment Scale. Residents and social workers completed post-study surveys. 37 evaluations were received, 20 completed by social workers and 17 resident self-evaluations. Social workers reported discussing plans with residents prior to conversations 90 % of the time (18/20, 95 % CI 64.5, 97.8). Social workers who had previously observed the resident delivering bad news reported that the resident was more skilled on subsequent encounters 90 % of the time (95 % CI 42.2, 99). Both social workers and residents felt that prior training or experience was important. First-year residents valued advice from social workers less than advice from attending physicians, whereas more experienced residents perceived advice from social workers to be equivalent with that of attending physicians (40 versus 2.9 %, p = 0.002). Social worker assessment of residents' abilities to deliver bad news is feasible and acceptable to both groups. This formalized self-assessment and evaluation process highlights the importance of social workers' involvement in delivery of bad news, and the teaching of this skill. This method may also be used as direct-observation for resident milestone assessment. PMID- 26892407 TI - Post-Hospital Outcomes of Patients With Acute Myocardial Infarction With Cardiogenic Shock: Findings From the NCDR. AB - BACKGROUND: Many patients with acute myocardial infarction (AMI) and cardiogenic shock survive hospitalization; little is known about their subsequent prognosis. OBJECTIVES: This study sought to evaluate the associations between cardiogenic shock and post-discharge mortality and all-cause hospitalization among hospital survivors. METHODS: We included patients >=65 years of age with AMI from the ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines) who survived hospitalization and linked these patients with Medicare claims data. We used proportional hazards models to test the association between cardiogenic shock and outcomes, adjusting for patient and hospital characteristics. Hazard ratios (HRs) are reported for early (1 to 60 days) and late (61 to 365 days) post-discharge time periods. RESULTS: Among 112,668 AMI survivors, 5% had cardiogenic shock during hospitalization. The rate of death was significantly higher among patients with cardiogenic shock at 60 days (9.6% vs. 5.5%) and 1 year (22.4% vs. 16.7%). After accounting for baseline characteristics, the risk of death remained higher for cardiogenic shock patients in the first 60 days after discharge (adjusted HR: 1.62; 95% confidence interval [CI]: 1.46 to 1.80), but was similar to nonshock patients thereafter (adjusted HR: 1.08 for days 61 to 365; 95% CI: 1.00 to 1.18). The rate of all-cause hospitalization or death was significantly higher among shock patients at 60 days (33.9% vs. 24.9%) and 1 year (59.1% vs. 52.3%). After adjustment, the risk of this outcome was also clustered in the first 60 days (adjusted HR: 1.28; 95% CI: 1.21 to 1.35) and was similar thereafter (adjusted HR: 0.95 for days 61 to 365; 95% CI: 0.89 to 1.01). CONCLUSIONS: Hospital survivors of AMI who had cardiogenic shock have a higher risk of death and/or hospitalization during the first year after discharge. The risk is time-dependent and is clustered in the early post discharge period, after which the prognosis is similar in patients with and without cardiogenic shock. PMID- 26892406 TI - Clinical practice guidelines for the management of neuropathic pain: a systematic review. AB - BACKGROUND: The management of neuropathic pain (NP) is challenging despite it being the recent focus of extensive research. A number of clinical practice guidelines (CPGs) for the management of NP have been published worldwide over the past 2 decades. This study aimed to assess the quality of these CPGs. METHODS: We performed a systematic review of published CPGs for the management of NP. Three reviewers independently assessed the quality of the CPGs using the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument, and recommendations of CPGs were also appraised. RESULTS: A total of 16 CPGs were included. Thirteen CPGs were developed using an evidence-based approach, and the remaining CPGs were produced by consensus panels. None of CPGs obtained a score greater than 50% in all six AGREE II instrument domains mainly owing to poor performance in the "Applicability" domain. The highest score of the CPGs was achieved in "Clarity and Presentation" domain, followed by "Scope and Purpose" and "Editorial Independence" domains, and the lowest scores were found the in "Applicability" domain. The majority of the CPG recommendations on the management of patients with NP were relatively consistent, especially regarding the recommendation of stepwise treatment with medication. CONCLUSIONS: Greater efforts are needed not only to improve the quality of development and presentation of the CPGs, but also to provide more efficacy evidence for the management of patients with NP. PMID- 26892408 TI - Cardiogenic Shock: How Long Does the Storm Last? PMID- 26892410 TI - Moving Toward Eradication of Stent Thrombosis. PMID- 26892409 TI - Safety and Efficacy of Everolimus- Versus Sirolimus-Eluting Stents: 5-Year Results From SORT OUT IV. AB - BACKGROUND: Long-term safety and efficacy for everolimus-eluting stents (EES) versus those of sirolimus-eluting stents (SES) are unknown. OBJECTIVES: This study compared 5-year outcomes for EES with those for SES from the SORT OUT IV (Scandinavian Organization for Randomized Trials with Clinical Outcome) trial. METHODS: Five-year follow-up was completed for 2,771 patients (99.9%). Primary endpoint was a composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and definite stent thrombosis. RESULTS: At 5-years, MACE occurred in 14.0% and 17.4% in the EES and SES groups, respectively (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.66 to 0.97; p = 0.02). The MACE rate did not differ significantly within the first year (HR: 0.96, 95% CI: 0.71 to 1.19; p = 0.79), but from years 1 through 5, the MACE rate was lower with EES (HR: 0.71, 95% CI: 0.55 to 0.90; p = 0.006; p interaction = 0.12). Definite stent thrombosis was lower with EES (0.4%) than with SES (2.0%; HR: 0.18, 95% CI: 0.07 to 0.46), with a lower risk of very late definite stent thrombosis in the EES group (0.2% vs. 1.4%, respectively; HR: 0.16, 95% CI: 0.05 to 0.53). When censoring the patients at the time of stent thrombosis, we found no significant differences between the 2 stent groups for MACE rates (HR: 0.89, 95% CI: 0.73 to 1.08; p = 0.23), target lesion revascularization (HR: 0.90, 95% CI: 0.64 to 1.27; p = 0.55), and MI (HR: 0.93, 95% CI: 0.64 to 1.36; p = 0.72). CONCLUSIONS: At 5-year follow-up, MACE rate was significantly lower with EES- than with SES-treated patients, due largely due to a lower risk of very late definite stent thrombosis. (Randomized Clinical Comparison of the Xience V and the Cypher Coronary Stents in Non selected Patients With Coronary Heart Disease [SORT OUT IV]; NCT00552877). PMID- 26892412 TI - Here Today, Gone Tomorrow. PMID- 26892411 TI - A Polylactide Bioresorbable Scaffold Eluting Everolimus for Treatment of Coronary Stenosis: 5-Year Follow-Up. AB - BACKGROUND: Long-term benefits of coronary stenosis treatment with an everolimus eluting bioresorbable scaffold are unknown. OBJECTIVES: This study sought to evaluate clinical and imaging outcomes 5 years after bioresorbable scaffold implantation. METHODS: In the ABSORB multicenter, single-arm trial, 45 (B1) and 56 patients (B2) underwent coronary angiography, intravascular ultrasound (IVUS), and optical coherence tomography (OCT) at different times. At 5 years, 53 patients without target lesion revascularization underwent final imaging. RESULTS: Between 6 months/1 year and 5 years, angiographic luminal late loss remained unchanged (B1: 0.14 +/- 19 mm vs. 0.13 +/- 0.33 mm; p = 0.7953; B2: 0.23 +/- 0.28 mm vs. 0.18 +/- 0.32 mm; p = 0.5685). When patients with a target lesion revascularization were included, luminal late loss was 0.15 +/- 0.20 mm versus 0.15 +/- 0.24 mm (p = 0.8275) for B1 and 0.30 +/- 0.37 mm versus 0.32 +/- 0.48 mm (p = 0.8204) for B2. At 5 years, in-scaffold and -segment binary restenosis was 7.8% (5 of 64) and 12.5% (8 of 64). On IVUS, the minimum lumen area of B1 decreased from 5.23 +/- 0.97 mm(2) at 6 months to 4.89 +/- 1.81 mm(2) at 5 years (p = 0.04), but remained unchanged in B2 (4.95 +/- 0.91 mm(2) at 1 year to 4.84 +/- 1.28 mm(2) at 5 years; p = 0.5). At 5 years, struts were no longer discernable by OCT and IVUS. On OCT, the minimum lumen area in B1 decreased from 4.51 +/- 1.28 mm(2) at 6 months to 3.65 +/- 1.39 mm(2) at 5 years (p = 0.01), but remained unchanged in B2, 4.35 +/- 1.09 mm(2) at 1 year and 4.12 +/- 1.38 mm(2) at 5 years (p = 0.24). Overall, the 5-year major adverse cardiac event rate was 11.0%, without any scaffold thrombosis. CONCLUSIONS: At 5 years, bioresorbable scaffold implantation in a simple stenotic lesion resulted in stable lumen dimensions and low restenosis and major adverse cardiac event rates. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856). PMID- 26892414 TI - The End Is Near... Do We Know Everything About Cardiopulmonary Exercise Testing in HF Patients? PMID- 26892413 TI - Variables Measured During Cardiopulmonary Exercise Testing as Predictors of Mortality in Chronic Systolic Heart Failure. AB - BACKGROUND: Data from a cardiopulmonary exercise (CPX) test are used to determine prognosis in patients with chronic heart failure (HF). However, few published studies have simultaneously compared the relative prognostic strength of multiple CPX variables. OBJECTIVES: The study sought to describe the strength of the association among variables measured during a CPX test and all-cause mortality in patients with HF with reduced ejection fraction (HFrEF), including the influence of sex and patient effort, as measured by respiratory exchange ratio (RER). METHODS: Among patients (n = 2,100, 29% women) enrolled in the HF-ACTION (HF-A Controlled Trial Investigating Outcomes of exercise traiNing) trial, 10 CPX test variables measured at baseline (e.g., peak oxygen uptake [Vo2], exercise duration, percent predicted peak Vo2 [%ppVo2], ventilatory efficiency) were examined. RESULTS: Over a median follow-up of 32 months, there were 357 deaths. All CPX variables, except RER, were related to all-cause mortality (all p < 0.0001). Both %ppVo2 and exercise duration were equally able to predict (Wald chi square: ~141) and discriminate (c-index: 0.69) mortality. Peak Vo2 (ml.kg( 1).min(-1)) was the strongest predictor of mortality among men (Wald chi-square: 129) and exercise duration among women (Wald chi-square: 41). Multivariable analyses showed that %ppVo2, exercise duration, and peak Vo2 (ml.kg(-1).min(-1)) were similarly able to predict and discriminate mortality. In men, a 10% 1-year mortality rate corresponded to a peak Vo2 of 10.9 ml.kg(-1).min(-1) versus 5.3 ml.kg(-1).min(-1) in women. CONCLUSIONS: Peak Vo2, exercise duration, and % ppVo2 carried the strongest ability to predict and discriminate the likelihood of death in patients with HFrEF. The prognosis associated with a given peak Vo2 differed by sex. (Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure; NCT00047437). PMID- 26892415 TI - Post-Operative Outcomes in Children With and Without Congenital Heart Disease Undergoing Noncardiac Surgery. AB - BACKGROUND: Significant advances have been made in the diagnosis and treatment of children with congenital heart disease (CHD), allowing for longer life expectancies and an increasing number who will require noncardiac surgery. OBJECTIVES: This study sought to compare the incidence of mortality and major adverse post-operative outcomes following noncardiac surgery in children with and without CHD. METHODS: Data from the 2012 pediatric database of the American College of Surgeons National Surgical Quality Improvement Program were analyzed. After propensity score matching, and stratification by severity of CHD, mortality and adverse post-operative outcomes were compared between controls and children with CHD. RESULTS: Among the 51,008 children included in the database, 4,520 children with CHD underwent noncardiac surgery. After propensity score matching, we included 2,805 children with minor CHD, 1,272 with major CHD, and 417 with severe CHD. Children in each subgroup were matched and compared with controls without CHD who underwent noncardiac surgery of comparable complexity. The incidence of overall mortality was significantly higher in children with moderate (3.9%) and severe (8.2%) CHD compared with their controls (respectively, 1.7% [p < 0.001] and 1.2% [p = 0.001]). Both 30-day and overall mortality were significantly increased in children with severe CHD (odds ratio [OR]: 8.43, 95% confidence interval [CI]: 2.52 to 28.21; p < 0.001; OR: 7.32, 95% CI: 2.83 to 18.90; p < 0.001) compared with their matched controls. Overall mortality was also significantly increased in children with major CHD compared with their controls (OR: 2.28; 95% CI: 1.37 to 3.79; p = 0.002), whereas no difference was observed between children with minor CHD and their matched controls. CONCLUSIONS: Children with major and severe CHD, undergoing noncardiac surgery, have an increased risk of mortality compared with children without CHD. Further studies need to identify the optimal environment for surgical procedures, develop trained multidisciplinary teams to care for children with CHD, and define management strategies for improving outcomes in this high-risk population. PMID- 26892416 TI - Assessing the Risks of Noncardiac Surgery for Children With Congenital Heart Disease. PMID- 26892418 TI - When Sweet Turns Salty: Glucose-Induced Suppression of Atrial Natriuretic Peptide by MicroRNA-425. PMID- 26892419 TI - Editor-in-Chief's Top Picks From 2015: Part Two. AB - Each week, I record audio summaries for every article in JACC, as well as an issue summary. While this process has been time-consuming, I have become very familiar with every paper that we publish. Thus, I have personally selected the papers (both original investigations and review articles) from 13 distinct specialties for your review. In addition to my personal choices, I have included manuscripts that have been the most accessed or downloaded on our websites, as well as those selected by the JACC Editorial Board members. There are approximately 130 articles selected across this 2-part series, which represent less than 3% of the papers submitted to the Journal in 2015. In order to present the full breadth of this important research in a consumable fashion, we will present these manuscripts over the course of 2 issues in JACC. Part One includes the sections: Congenital Heart Disease, Coronary Disease & Interventions, CVD Prevention & Health Promotion, Cardiac Failure, Cardiomyopathies, Genetics, Omics, & Tissue Regeneration, and Hypertension. Part Two includes the sections: Imaging, Metabolic Disorders & Lipids, Rhythm Disorders, Statistics, Valvular Heart Disease, and Vascular Medicine (1-63). PMID- 26892421 TI - The Seven Deadly Sins of Health Care: Part I. PMID- 26892422 TI - Pre-Publication in Medical Research: A Race to Open Pandora's Box? PMID- 26892417 TI - Acute Metabolic Influences on the Natriuretic Peptide System in Humans. AB - BACKGROUND: The cardiac natriuretic peptides (NPs), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), have central roles in sodium and blood pressure regulation. Extracardiac factors (e.g., obesity and diabetes) influence NP production, potentially altering cardiovascular responses to volume and pressure stress. OBJECTIVES: This study examined the effects of acute carbohydrate intake on the NP system in humans, and investigated underlying mechanisms. METHODS: Normotensive subjects (N = 33) were given a high carbohydrate shake. Venous blood was sampled to measure N-terminal (NT)-proANP and NT-proBNP levels. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and HepG2 cells were treated with glucose, and expression levels of NPs and micro ribonucleic acid 425 (miR-425), a negative regulator of ANP, were examined. The role of nuclear factor kappa B (NF-kappaB) in the glucose-mediated effects was investigated using a NF-kappaB inhibitor and expression plasmids encoding NF kappaB subunits. RESULTS: We observed a 27% reduction in the levels of circulating NT-proANP (p < 0.001, maximal at 6 h) after carbohydrate challenge, with no effect on NT-proBNP levels in our human subjects. Glucose treatment of hESC-CMs for 6 h and 24 h increased levels of the primary transcript of miR-425 (pri-miR-425) and mature miR-425. A corresponding decrease in NPPA messenger RNA levels was also observed at both time points. Overexpression of NF-kappaB subunits in H9c2 cardiomyocytes increased miR-425 levels, whereas inhibition of NF-kappaB abrogated the glucose-mediated increase in pri-miR-425 levels in HepG2 cells. CONCLUSIONS: Acute carbohydrate challenge is associated with a reduction in ANP production. The mechanism appears to involve a glucose-induced increase in the expression of miR-425, mediated by NF-kappaB signaling. PMID- 26892420 TI - Diagnostic Strategies for the Evaluation of Chest Pain: Clinical Implications From SCOT-HEART and PROMISE. AB - SCOT-HEART (Scottish COmputed Tomography of the HEART) and PROMISE (PROspective Multicenter Imaging Study for Evaluation of chest pain) represent the 2 largest and most comprehensive cardiovascular imaging outcome trials in patients with stable chest pain and provide significant insights into patient diagnosis, management, and outcomes. These trials are particularly timely, given the well recognized knowledge gaps and widespread use of noninvasive imaging. The overall goal of this review is to distill the data generated from these 2 pivotal trials to better inform the practicing clinician in the selection of noninvasive testing for stable chest pain. Similarities and differences between SCOT-HEART and PROMISE are highlighted, and clinical and practical implications are discussed. Both trials show that coronary computed tomography angiography should have a greater role in the diagnostic pathway of patients with stable chest pain. PMID- 26892423 TI - Student Debt in American Medicine: I Am Not a Loan! PMID- 26892424 TI - Transfemoral Tricuspid Valve Repair Using a Percutaneous Mitral Valve Repair System. PMID- 26892425 TI - Bridging Anticoagulation. PMID- 26892426 TI - Reply: Bridging Anticoagulation. PMID- 26892427 TI - Incidence of Stent Thrombosis With Bioresorbable Vascular Scaffolds in Comparison With Drug-Eluting Stents. PMID- 26892428 TI - Reply: Incidence of Stent Thrombosis With Bioresorbable Vascular Scaffolds in Comparison With Drug-Eluting Stents. PMID- 26892429 TI - The nature of hydrogen-bonding interaction in the prototypic hybrid halide perovskite, tetragonal CH3NH3PbI3. AB - In spite of the key role of hydrogen bonding in the structural stabilization of the prototypic hybrid halide perovskite, CH3NH3PbI3 (MAPbI3), little progress has been made in our in-depth understanding of the hydrogen-bonding interaction between the MA(+)-ion and the iodide ions in the PbI6-octahedron network. Herein, we show that there exist two distinct types of the hydrogen-bonding interaction, naming alpha- and beta-modes, in the tetragonal MAPbI3 on the basis of symmetry argument and density-functional theory calculations. The computed Kohn-Sham (K-S) energy difference between these two interaction modes is 45.14 meV per MA-site with the alpha-interaction mode being responsible for the stable hydrogen-bonding network. The computed bandgap (Eg) is also affected by the hydrogen-bonding mode, with Eg of the alpha-interaction mode (1.73 eV) being significantly narrower than that of the beta-interaction mode (2.03 eV). We have further estimated the individual bonding strength for the ten relevant hydrogen bonds having a bond critical point. PMID- 26892432 TI - Availability of plethora of bioanalytical assays for several commonly prescribed drugs - a problem of plenty: perspectives. PMID- 26892431 TI - Runx1 contributes to the functional switching of bone morphogenetic protein 4 (BMP4) from neurite outgrowth promoting to suppressing in dorsal root ganglion. AB - The runt-related transcription factor Runx1 regulates cell-type specification and axonal projections of nociceptive dorsal root ganglion (DRG) neurons, whereas bone morphogenetic protein 4 (BMP4) is required for axonal growth during neuronal development. Although Runx1 has been shown to be involved in BMP4 signaling in non-neural tissues, the Runx1 function in BMP4-dependent regulation of neuronal development is unclear. To investigate interactions between Runx1 and BMP4 in neurite outgrowth, we cultured DRGs from wild-type and Runx1-deficient mouse embryos in the presence or absence of BMP4. Neurite outgrowth was decreased in BMP4-treated wild-type DRGs and untreated Runx1-deficient DRGs, suggesting the inhibitory effect of BMP4 and facilitatory effect of Runx1 on neurite outgrowth. In addition, the combination of BMP4 treatment and Runx1 deficiency increased neurite outgrowth, suggesting that Runx1 is required for BMP4-induced suppression of neurite outgrowth and that the loss of Runx1 results in a functional switch of BMP4 from neurite growth suppressing to neurite growth promoting. Both BMP4 treatment and Runx1 deficiency increased calcitonin gene-related peptide (CGRP) positive neurons, and CGRP expression was not increased by BMP4 treatment in Runx1-deficient mice, suggesting that Runx1 contributes to BMP4-induced CGRP expression in DRG neurons. Thus, Runx1 contributes to BMP4 regulation of neurite outgrowth and CGRP expression in DRG and may control BMP4 functional switching during embryogenesis. PMID- 26892430 TI - Systemic inflammation is an independent predictive marker of clinical outcomes in mucosal squamous cell carcinoma of the head and neck in oropharyngeal and non oropharyngeal patients. AB - BACKGROUND: Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence and shortened survival. This study aimed to investigate whether a marker of systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive of clinical outcomes in a heterogeneous cohort of HNSCC cancer patients. METHODS: We performed a retrospective analysis to identify associations between NLR and clinicopathological features to recurrence free survival (RFS) and overall survival (OS). Univariate analysis was used to identify associations and selected variables were included in multivariable Cox regression analysis to determine predictive value. RESULTS: A total of 145 patients with stage I-IV HNSCC that had undergone radiotherapy were analysed. Seventy-six of these patients had oropharyngeal cancer and 69 had non-oropharyngeal HNSCC and these populations were analysed separately. NLR was not associated to any clinicopathological variable. On univariate analysis, NLR showed associations with RFS and OS in both sub-populations. Multivariable analysis showed patients with NLR > 5 had shortened OS in both sub-populations but NLR > 5 only predicted RFS in oropharyngeal patients. Poor performance status predicted OS in both sub populations and current smokers had shortened OS and RFS in non-oropharyngeal patients. CONCLUSIONS: The results show patients with NLR > 5 predict for shorter overall survival. Further prospective validation studies in larger cohorts are required to determine the clinical applicability of NLR for prognostication in HNSCC patients. PMID- 26892433 TI - Antiproliferative and apoptosis induction of alpha-mangostin in T47D breast cancer cells. AB - alpha-Mangostin extracted from mangosteen, Garcinia mangostana Linn. is known as 'queen of fruits'. The anticancer activity of alpha-mangostin through apoptosis induction and related signaling pathways in human breast cancer T47D cells was investigated. Human epidermal growth factor receptor 2 (HER2) and mitogen activated protein kinase (MAPK) signaling have been shown to play important roles in apoptosis. The results showed that alpha-mangostin induced cell proliferation inhibition, DNA fragmentation, nuclear condensation, increased cleaved caspase-3 and cleaved caspase-9, but decreased Bcl-2 and Mcl-1 expression. Mitochondrial dysfunction and cytochrome c release were also detected. In addition, phosphorylation of ERalpha, HER2, PI3K, Akt and ERK1/2 were downregulated whereas p-JNK1/2 and p-p38 were upregulated. These results indicated that alpha-mangostin induced apoptosis associated with HER2/PI3K/Akt and MAPK signaling pathways suggesting that alpha-mangostin may be used as food supplement or a potential therapeutic compound for breast cancer. PMID- 26892436 TI - Placental Inflammatory Response to Zika Virus may Affect Fetal Brain Development. PMID- 26892434 TI - Hydrophobic bile acids relax rat detrusor contraction via inhibiting the opening of the Na+/Ca2+ exchanger. AB - Hydrophobic bile acids (BAs) are thought to inhibit smooth muscle contractility in several organs. The present study was undertaken to investigate the effects of hydrophobic BAs on the detrusor contractility of rat bladder and to explore the possible mechanism. Lithocholic acid (LCA) treatment increased the micturition interval and induced a concentration-dependent relaxation of bladder detrusor strips. In addition, LCA reduced the concentration of intracellular free Ca(2+)([Ca(2+)]i) and inhibited both the outward and inward Na(+)/Ca(2+) exchanger (NCX) current (INCX) in primary isolated smooth muscle cells (SMCs). To further investigate the mechanism of action of LCA, several pharmacologic agents were used. We found that the NCX inhibitor 3',4'-Dichlorobenzamil (DCB) can significantly inhibit the relaxation of detrusor strips and a reduction of the [Ca(2+)]i induced by LCA, while the antagonist of muscarinic receptor and the agonist of the G protein-coupled bile acid receptor (TGR5) and the farnesoid X receptor (FXR) had no effect. In conclusion, these data suggest that the relaxation of rat detrusor induced by hydrophobic BAs is mediated by NCX. Further research is needed to carry out to demonstrate the possible pathway and provide a potential new strategy to investigation for the treatment of the low urinary tract syndromes. PMID- 26892435 TI - A review of approaches for dental practice teams for promoting oral health. AB - To determine the circumstances in which oral health promotion (OHP) in General Dental Practice is at its most effective, a systematic review was conducted to identify, critically appraise and synthesize the available evidence. The research question was: Is oral health promotion within dental practice effective and how can its effects be optimized? Systematic searches of 20 online resources (including Ovid Medline and Embase) were conducted. A call for evidence was also issued, and citation lists of other relevant systematic reviews were included. All studies published since 1994 which were set in the context of general dental practice and investigated promoting good oral health in adult or child patients were considered. 44 studies reported in 52 papers were included in the review. The evidence was heterogeneous and the quality of reporting was variable. Results showed that oral health promotion based on behavioural and psychological models was effective for improving oral health. Verbal advice affected knowledge and reported behaviour, written advice promoted oral health knowledge. There was moderate evidence that the attributes of the 'sender' of an oral health promotion message influenced its effectiveness. Many barriers and facilitators were shown to influence the effectiveness of OHP in dental practice. The results of this review suggest that the psychology of behaviour change is the key to oral health promotion and greater emphasis on teaching oral health professionals about health psychology would make oral health promotion in the dental surgery more effective. PMID- 26892438 TI - 35 Hz shape memory alloy actuator with bending-twisting mode. AB - Shape Memory Alloy (SMA) materials are widely used as an actuating source for bending actuators due to their high power density. However, due to the slow actuation speed of SMAs, there are limitations in their range of possible applications. This paper proposes a smart soft composite (SSC) actuator capable of fast bending actuation with large deformations. To increase the actuation speed of SMA actuator, multiple thin SMA wires are used to increase the heat dissipation for faster cooling. The actuation characteristics of the actuator at different frequencies are measured with different actuator lengths and results show that resonance can be used to realize large deformations up to 35 Hz. The actuation characteristics of the actuator can be modified by changing the design of the layered reinforcement structure embedded in the actuator, thus the natural frequency and length of an actuator can be optimized for a specific actuation speed. A model is used to compare with the experimental results of actuators with different layered reinforcement structure designs. Also, a bend-twist coupled motion using an anisotropic layered reinforcement structure at a speed of 10 Hz is also realized. By increasing their range of actuation characteristics, the proposed actuator extends the range of application of SMA bending actuators. PMID- 26892437 TI - A highly active and stable hydrogen evolution catalyst based on pyrite-structured cobalt phosphosulfide. AB - Rational design and controlled synthesis of hybrid structures comprising multiple components with distinctive functionalities are an intriguing and challenging approach to materials development for important energy applications like electrocatalytic hydrogen production, where there is a great need for cost effective, active and durable catalyst materials to replace the precious platinum. Here we report a structure design and sequential synthesis of a highly active and stable hydrogen evolution electrocatalyst material based on pyrite structured cobalt phosphosulfide nanoparticles grown on carbon nanotubes. The three synthetic steps in turn render electrical conductivity, catalytic activity and stability to the material. The hybrid material exhibits superior activity for hydrogen evolution, achieving current densities of 10 mA cm(-2) and 100 mA cm(-2) at overpotentials of 48 mV and 109 mV, respectively. Phosphorus substitution is crucial for the chemical stability and catalytic durability of the material, the molecular origins of which are uncovered by X-ray absorption spectroscopy and computational simulation. PMID- 26892439 TI - The use of 3D printed external and internal templates for Bonebridge implantation - technical note. PMID- 26892440 TI - Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy. AB - BACKGROUND: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy. MATERIALS & METHODS: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy. RESULTS: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses. CONCLUSION: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively. PMID- 26892445 TI - Highly Dispersible and Stable Anionic Boron Cluster-Graphene Oxide Nanohybrids. AB - An efficient process to produce boron cluster-graphene oxide nanohybrids that are highly dispersible in water and organic solvents is established for the first time. Dispersions of these nanohybrid materials in water were extraordinarily stable after one month. Characterization of hybrids after grafting of appropriate cobaltabisdicarbollide and closo-dodecaborate derivatives onto the surface of graphene oxide (GO) was done by FT-IR, XPS, and UV/Vis. Thermogravimetric analysis (TGA) clearly shows a higher thermal stability for the modified-GO nanohybrids compared to the parent GO. Of particular note, elemental mapping by energy-filtered transmission electron microscopy (EFTEM) reveals that a uniform decoration of the graphene oxide surface with the boron clusters is achieved under the reported conditions. Therefore, the resulting nanohybrid systems show exceptional physico-chemical and thermal properties, paving the way for an enhanced processability and further expanding the range of application for graphene-based materials. PMID- 26892444 TI - Clinical audit of genetic testing and referral patterns for fragile X and associated conditions. AB - An audit was conducted of laboratory/clinical databases of genetic tests performed between January 2003 and December 2009, and for 2014, as well as referrals to the clinical service and a specialist multidisciplinary clinic, to determine genetic testing request patterns for fragile X syndrome and associated conditions and referrals for genetic counseling/multidisciplinary management in Victoria, Australia. An expanded allele (full mutation, premutation or intermediate) was found in 3.7% of tests. Pediatricians requested ~70% of test samples, although fewer general practitioners and more obstetricians/gynecologists ordered tests in 2014. Median age at testing for individuals with a full mutation seeking a diagnosis without a fragile X family history was 4.3 years (males) and 9.4 years (females); these ages were lower when pediatricians ordered the tests (2.1 years and 6.1 years, respectively). Individuals with a premutation were generally tested at a later age (median age: males, 33.2 years; females, 36.4 years). Logistic regression showed that a family history of ID (OR 3.28 P = 0.005, CI 1.77-5.98) was the only indication to independently increase the likelihood of a test-positive (FM or PM) result. Following testing, ~25% of full mutation or premutation individuals may not have attended clinical services providing genetic counseling or multidisciplinary management for these families. The apparent delay in fragile X syndrome diagnosis and lack of appropriate referrals for some may result in less than optimal management for these families. These findings suggest continued need for awareness and education of health professionals around diagnosis and familial implications of fragile X syndrome and associated conditions. (c) 2016 Wiley Periodicals, Inc. PMID- 26892442 TI - Clinicopathologic and prognostic associations of KRAS and BRAF mutations in small intestinal adenocarcinoma. AB - Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) chemotherapy in colorectal cancer. But the status of KRAS and BRAF mutations and their clinicopathologic and prognostic significance has not been extensively evaluated in small intestinal adenocarcinomas. In this work, the KRAS and BRAF genes in 190 surgically resected small intestinal adenocarcinoma cases were sequenced and their association with various clinicopathologic variables, including survival of the patients, was analyzed. KRAS or BRAF mutations were observed in 63 (33%) cases. Sixty-one cases had KRAS mutations and 2 had BRAF mutations and the two types of mutation were mutually exclusive. The majority of KRAS mutations were G>A transition (43/61 cases, 71%) or p.G12D (31/61 cases, 51%). The patients with mutant KRAS tended to have higher pT classifications (P=0.034) and more frequent pancreatic invasion (P=0.020) than those with wild-type KRAS. Multivariate logistic regression analysis showed that certain mutated KRAS subtypes (G>A transitions and G12D mutations) were significantly correlated with higher pT classification (P=0.015 and 0.004, respectively) than wild-type KRAS and other KRAS mutations. The patients with KRAS or BRAF mutation had a tendency to shorter overall survival than those with wild-type KRAS and BRAF (P=0.148), but subgroup analysis demonstrated the patients with KRAS mutations showed worse survival (median, 46.0 months; P=0.046) than those with wild-type KRAS (85.4 months) in lower pT classification (pT1-pT3) group. In summary, KRAS and, infrequently, BRAF mutations are observed in a subset of small intestinal adenocarcinomas, and are associated with higher pT classification and more frequent pancreatic invasion. KRAS mutation is a poor prognostic predictor in patients with lower pT classification tumors. Anti-EGFR targeted therapy could be applied to about two thirds of small intestinal adenocarcinoma patients, namely those with wild-type KRAS and BRAF if they have metastatic disease, similar to colorectal cancer patients. PMID- 26892441 TI - Intravenous leiomyomatosis: an unusual intermediate between benign and malignant uterine smooth muscle tumors. AB - Intravenous leiomyomatosis is an unusual smooth muscle neoplasm with quasi malignant intravascular growth but a histologically banal appearance. Herein, we report expression and molecular cytogenetic analyses of a series of 12 intravenous leiomyomatosis cases to better understand the pathogenesis of intravenous leiomyomatosis. All cases were analyzed for the expression of HMGA2, MDM2, and CDK4 proteins by immunohistochemistry based on our previous finding of der(14)t(12;14)(q14.3;q24) in intravenous leiomyomatosis. Seven of 12 (58%) intravenous leiomyomatosis cases expressed HMGA2, and none expressed MDM2 or CDK4. Colocalization of hybridization signals for probes from the HMGA2 locus (12q14.3) and from 14q24 by interphase fluorescence in situ hybridization (FISH) was detected in a mean of 89.2% of nuclei in HMGA2-positive cases by immunohistochemistry, but in only 12.4% of nuclei in negative cases, indicating an association of HMGA2 expression and this chromosomal rearrangement (P=8.24 * 10(-10)). Four HMGA2-positive cases had greater than two HMGA2 hybridization signals per cell. No cases showed loss of a hybridization signal by interphase FISH for the frequently deleted region of 7q22 in uterine leiomyomata. One intravenous leiomyomatosis case analyzed by array comparative genomic hybridization revealed complex copy number variations. Finally, expression profiling was performed on three intravenous leiomyomatosis cases. Interestingly, hierarchical cluster analysis of the expression profiles revealed segregation of the intravenous leiomyomatosis cases with leiomyosarcoma rather than with myometrium, uterine leiomyoma of the usual histological type, or plexiform leiomyoma. These findings suggest that intravenous leiomyomatosis cases share some molecular cytogenetic characteristics with uterine leiomyoma, and expression profiles similar to that of leiomyosarcoma cases, further supporting their intermediate, quasi-malignant behavior. PMID- 26892446 TI - Development and preliminary validation of a leadership competency instrument for existing and emerging allied health professional leaders. AB - BACKGROUND: No instruments, to our knowledge, exist to assess leadership competency in existing and emerging allied health professional (AHP) leaders. This paper describes the development and preliminary exploration of the psychometric properties of a leadership competency instrument for existing and emerging AHP leaders and examines (i) its factor structure, (ii) its convergent validity with the Leadership Practices Inventory (LPI), and (iii) its discriminative validity in AHPs with different grades. METHODS: During development, we included 25 items in the AHEAD (Aspiring leaders in Healthcare Empowering individuals, Achieving excellence, Developing talents) instrument. A cross-sectional study was then conducted in 106 high-potential AHPs from Singapore General Hospital (34 men and 72 women) of different professional grades (49 principal-grade AHPs, 41 senior-grade AHPs, and 16 junior-grade AHPs) who completed both AHEAD and LPI instruments. Exploratory factor analysis was used to test the theoretical structure of AHEAD. Spearman correlation analysis was performed to evaluate the convergent validity of AHEAD with LPI. Using proportional odds regression models, we evaluated the association of grades of AHPs with AHEAD and LPI. To assess discriminative validity, the c-statistics - a measure of discrimination - were derived from these ordinal models. RESULTS: As theorized, factor analysis suggested a two-factor solution, where "skills" and "values" formed separate factors. Internal consistency of AHEAD was excellent (alpha-values > 0.88). Total and component AHEAD and LPI scores correlated moderately (Spearman rho-values, 0.37 to 0.58). The c-index for discriminating between AHP grades was higher for AHEAD than for the LPI (0.76 vs. 0.65). CONCLUSION: The factorial structure of AHEAD was generally supported in our study. AHEAD showed convergent validity with the LPI and outperformed the LPI in terms of discriminative validity. These results provide initial evidence for the use of AHEAD to assess leadership competency in AHPs. PMID- 26892443 TI - The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing. AB - Kinase activation by chromosomal translocations is a common mechanism that drives tumorigenesis in spitzoid neoplasms. To explore the landscape of fusion transcripts in these tumors, we performed whole-transcriptome sequencing using formalin-fixed, paraffin-embedded (FFPE) tissues in malignant or biologically indeterminate spitzoid tumors from 7 patients (age 2-14 years). RNA sequence libraries enriched for coding regions were prepared and the sequencing was analyzed by a novel assembly-based algorithm designed for detecting complex fusions. In addition, tumor samples were screened for hotspot TERT promoter mutations, and telomerase expression was assessed by TERT mRNA in situ hybridization (ISH). Two patients had widespread metastasis and subsequently died of disease, and 5 patients had a benign clinical course on limited follow-up (mean: 30 months). RNA sequencing and TERT mRNA ISH were successful in six tumors and unsuccessful in one disseminating tumor because of low RNA quality. RNA sequencing identified a kinase fusion in five of the six sequenced tumors: TPM3 NTRK1 (2 tumors), complex rearrangements involving TPM3, ALK, and IL6R (1 tumor), BAIAP2L1-BRAF (1 tumor), and EML4-BRAF (1 disseminating tumor). All predicted chimeric transcripts were expressed at high levels and contained the intact kinase domain. In addition, two tumors each contained a second fusion gene, ARID1B-SNX9 or PTPRZ1-NFAM1. The detected chimeric genes were validated by home brew break-apart or fusion fluorescence in situ hybridization (FISH). The two disseminating tumors each harbored the TERT promoter -124C>T (Chr 5:1,295,228 hg19 coordinate) mutation, whereas the remaining five tumors retained the wild type gene. The presence of the -124C>T mutation correlated with telomerase expression by TERT mRNA ISH. In summary, we demonstrated complex fusion transcripts and novel partner genes for BRAF by RNA sequencing of FFPE samples. The diversity of gene fusions demonstrated by RNA sequencing defines the molecular heterogeneity of spitzoid neoplasms. PMID- 26892447 TI - Protective effect of wogonin on endotoxin-induced acute lung injury via reduction of p38 MAPK and JNK phosphorylation. AB - Acute lung injury (ALI) is a serious inflammatory disorder which remains the primary cause of incidence and mortality in patients with acute pulmonary inflammation. However, there is still no effective medical strategy available clinically for the improvement of ALI. Wogonin, isolated from roots of Scutellaria baicalensis Georgi, is a common medicinal herb which presents biological and pharmacological effects, including antioxidation, anti inflammation, and anticancer. Preadministration of wogonin inhibited not only lung edema but also protein leakage into the alveolar space in murine model of lipopolysaccharide (LPS)-induced ALI. Moreover, wogonin not only reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also inhibited the phosphorylation of mitogen-activated protein kinase (MAPK) induced by LPS. We further found wogonin inhibited the phosphorylation of p38 MAPK and JNK at a concentration lower than ERK. In addition, inhibition of lung edema, protein leakage, expression of iNOS and COX-2, and phosphorylation of p38 MAPK and JNK were all observed in a parallel concentration-dependent manner. These results suggest that wogonin possesses potential protective effect against LPS-induced ALI via downregulation of iNOS and COX-2 expression by blocking phosphorylation of p38 MAPK and JNK. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 397-403, 2017. PMID- 26892448 TI - Anticoagulation, CHA2DS2VASc Score, and Thromboembolic Risk of Cardioversion of Acute Atrial Fibrillation (from the FinCV Study). AB - The efficacy of the anticoagulation in preventing thromboembolic complications (TEC) and the usefulness of the CHA2DS2VASc score for assessing stroke risk during cardioversion of acute atrial fibrillation (AF) are unclear. Thus, our objectives were to assess the ability of the CHA2DS2VASc score to predict TEC and to evaluate the efficacy of anticoagulation in the prevention of TEC in Finnish CardioVersion (FinCV) study. The FinCV is a retrospective, multicenter study of 3,143 patients, who underwent 7,660 cardioversions for acute AF. The value of the CHA2DS2VASc score in predicting TEC was analyzed separately in cardioversions performed without and with anticoagulation. A total of 40 definite TEC (0.6%) occurred after 7,237 successful cardioversions and 1 stroke (0.2%) after 423 unsuccessful procedures. In 5,362 cardioversions performed without anticoagulation, the risk of definite TEC increased significantly from 0.4% in patients with a CHA2DS2VASc score of 0 to 1 to 2.3% in those with score of >=5 (p <0.001 for trend). The C-statistic of the CHA2DS2VASc score was 0.72 (0.61 to 0.83) in predicting definite TEC in non-anticoagulated patients with first cardioversion. The incidence of definite TEC was significantly lower in 2,298 cardioversions performed during anticoagulation (0.1% vs 0.7%, p = 0.001), and the preventive effect of anticoagulation was significant in patients with a score of >=2 (0.2% vs 1.1%, p = 0.001). In conclusion, CHA2DS2VASc score is a strong predictor of TEC in cardioversion of acute AF performed without anticoagulation. Importantly, periprocedural anticoagulation reduced the risk of TEC by 82%. The overall risk of these complications was low after failed cardioversion. PMID- 26892449 TI - Better Diagnosis of Functionally Significant Intermediate Sized Narrowings Using Intravascular Ultrasound-Minimal Lumen Area and Coronary Computed Tomographic Angiography-Based Myocardial Segmentation. AB - Lesion morphology poorly predicts functional significance of intermediate coronary artery stenosis. The aim of this study was to determine whether a coronary artery-based myocardial segmentation method that quantifies subtended myocardium can improve the diagnostic accuracy of intravascular ultrasound (IVUS) derived parameters for detecting ischemia-producing lesions. Coronary computed tomography angiography, IVUS, and fractional flow reserve (FFR) data were analyzed in 101 non-left main lesions (20% to 80% angiographic stenosis). Using the coronary artery-based myocardial segmentation method, total left ventricular myocardial volume (Vtotal), myocardial volume subtended by the stenotic coronary segment (Vsub), and Vratio (the ratio of the Vsub to the Vtotal) were assessed. Both Vsub >30.7 cm(3) and Vratio >25.4% were determinants of FFR <=0.75 (area under the curve = 0.696 and 0.744). Overall, an IVUS-measured minimum lumen area (IVUS-MLA) <=2.83 mm(2) predicted FFR <=0.75 with a sensitivity 88% and specificity 73%. Among lesions with IVUS-MLA <=2.83 mm(2) and FFR >0.75, 89% showed Vsub <30.7 cm(3). In 50 lesions with Vsub >30.7 cm(3), an IVUS-MLA <=2.85 mm(2) predicted FFR <=0.75 with sensitivity 85%, specificity 92%, positive predictive value 92%, and negative predictive value 85%. Conversely, in 51 lesions with a Vsub <=30.7 cm(3), IVUS-MLA <=2.67 mm(2) showed sensitivity 100%, specificity 69%, positive predictive value 38%, and negative predictive value 100% for predicting FFR <=0.75. Body surface area, reference lumen diameter, and vessel area had modest correlations with Vsub. In those lesion subsets, IVUS-MLA ~2.8 mm(2) accurately predicted an FFR <=0.75, whereas the clinical relevance of assessing and treating lesions with a smaller myocardial territory may be limited (ClinicalTrials.gov number NCT1696006). PMID- 26892450 TI - Association of Late Gadolinium Enhancement and Degree of Left Ventricular Hypertrophy Assessed on Cardiac Magnetic Resonance Imaging With Ventricular Tachycardia in Children With Hypertrophic Cardiomyopathy. AB - There are limited data on the clinical significance of left ventricular (LV) mass and late gadolinium enhancement (LGE) in pediatric hypertrophic cardiomyopathy (HC). We reviewed cardiovascular magnetic resonance (CMR) studies of children with HC to investigate the associations between the extent and distribution of LGE and LV mass with ventricular tachycardia (VT) in children with HC. A blinded observer reviewed CMR studies for the presence and distribution of LV hypertrophy and LGE using a 17-segment model. The primary outcome was VT. LGE was present 17 of 33 subjects (52%). VT was present on outpatient Holter monitor or exercise stress test in 7 patients, of which 5 patients (71%) had LGE. Each additional segment of LGE was associated with an increase in the odds of VT (odds ratio [OR] 1.4, 95% CI 1.1 to 1.9) and fewer than 5 segments with LGE had 93% specificity for the presence or absence of VT (OR 0.06, 95% CI 0.01 to 0.5). VT was more common in patients with LGE in the apical septal (p = 0.03), basal inferoseptal (p <0.01), and basal inferior (p = 0.04) segments, whereas LGE in more commonly involved segments (midanteroseptal and midinferoseptal) was not associated with VT (p = 0.13, 0.26). Patients with VT had greater LV mass index (76.4 +/- 40.4 g/m(2.7) vs 50.9 +/- 24.3 g/m(2.7); p = 0.03). Each centimeter of increased maximum LV thickness was associated with increased likelihood of VT (OR 2.9, 95% CI 1.2 to 6.8). In conclusion, in pediatric HC, CMR to evaluate the extent and pattern of LGE, LV mass index, and maximum LV thickness may help to identify children with HC at risk of VT. PMID- 26892451 TI - Impact of Anesthesia Type on Outcomes of Transcatheter Aortic Valve Implantation (from the Multicenter ADVANCE Study). AB - Transcatheter aortic valve implantation (TAVI) has become the standard of care for many patients with symptomatic severe aortic stenosis who are at increased risk of morbidity and mortality during surgical aortic valve replacement. However, there is still no general consensus regarding the use of general anesthesia (GA) versus local anesthesia with sedation (non-GA) during the TAVI procedure. Using propensity score-matching analysis, we analyzed the characteristics and outcomes of patients who underwent TAVI with either GA (n = 245) or non-GA (n = 245) in the fully monitored, international, CoreValve ADVANCE Study. No statistically significant differences existed between the non-GA and GA groups in all-cause mortality (25.4% vs 23.9%, p = 0.78), cardiovascular mortality (16.4% vs 16.6%, p = 0.92), or stroke (5.2% vs 6.9%, p = 0.57) through 2-year follow-up. Major vascular complications were more common in the non-GA group. Total hospital stay was similar between the 2 groups. Conversion from non GA to GA occurred in 13 patients (5.3%) because of procedural complications in 9 patients and discomfort or restlessness in 4 patients. Most procedural complications were related to valve positioning or vascular issues. Two of the 13 converted patients died during the procedure. Both GA and non-GA are widely used in real-world TAVI practice, and the decision appears to be guided by only a few patient-related factors and dominated by local and national practice. The outcomes of both anesthesia modes are equally good. When conversion from non-GA did occur, the complication requiring GA affected outcomes. PMID- 26892452 TI - Meta-Analysis of Radial Versus Femoral Artery Approach for Coronary Procedures in Patients With Previous Coronary Artery Bypass Grafting. AB - Cardiac catheterization through the radial artery approach (RA) has been shown to significantly reduce access-site complications compared with the femoral artery approach (FA) in many clinical settings. However, in the subset of patients with previous coronary artery bypass grafting (CABG), optimal vascular access site for coronary angiography and intervention is still a matter of debate. We aimed to perform a systematic review and meta-analysis of available studies comparing RA with FA in patients with previous CABG. Data were extracted by two independent reviewers; weighted mean differences and 95% confidence interval (CI) were calculated for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for dichotomous outcomes. Summary statistics were calculated by random effects model using Review Manager 5.3 software. The meta-analysis included 1 randomized and 8 nonrandomized studies, with a total of 2,763 patients. Compared with FA, RA required similar procedural time (mean difference 3.24 minutes, 95% CI -1.76 to 8.25, p = 0.20), fluoroscopy time (mean difference 0.62 minutes, 95% CI -0.83 to 2.07, p = 0.40), and contrast volume (mean difference -2.58 ml, 95% CI -18.36 to 13.20, p = 0.75) and was associated with similar rate of procedural failure (OR 1.32, 95% CI 0.63 to 2.80, p = 0.46), higher rate of crossover to another vascular access (OR 7.0, 95% CI 2.74 to 17.87, p <0.0001), and lower risk of access-site complications (OR 0.46, 95%CI 0.26 to 0.80, p = 0.006). In conclusion, the present meta-analysis suggests that in patients with previous CABG undergoing coronary procedures, RA, compared with FA, is associated with increased crossover rate but may reduce access-site complications. PMID- 26892453 TI - Biocompatible multilayer capsules engineered with a graphene oxide derivative: synthesis, characterization and cellular uptake. AB - Graphene-based capsules have strong potential for a number of applications, including drug/gene delivery, tissue engineering, sensors, catalysis and reactors. The ability to integrate graphene into carrier systems with three dimensional (3D) geometry may open new perspectives both for fundamental tests of graphene mechanics and for novel (bio)technological applications. However, the assembly of 3D complexes from graphene or its derivatives is challenging because of its poor stability under biological conditions. In this work, we attempted to integrate a layer of graphene oxide derivative into the shell of biodegradable capsules by exploiting a facile layer-by-layer (LbL) protocol. As a first step we optimized the LbL protocol to obtain colloidal suspensions of isolated capsules embedding the graphene oxide derivative. As a following step, we investigated in detail the morphological properties of the hybrid capsules, and how the graphene oxide derivative layer influences the porosity and the robustness of the multilayer composite shells. Finally, we verified the uptake of the capsules modified with the GO derivative by two cell lines and studied their intracellular localization and biocompatibility. As compared to pristine capsules, the graphene modified capsules possess reduced porosity, reduced shell thickness and a higher stability against osmotic pressure. They show remarkable biocompatibility towards the tested cells and long-term colloidal stability and dispersion. By combining the excellent mechanical properties of a graphene oxide derivative with the high versatility of the LbL method, robust and flexible biocompatible polymeric capsules with novel characteristics have been fabricated. PMID- 26892454 TI - Erratum to: PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events. PMID- 26892455 TI - An Improved CAD System for Breast Cancer Diagnosis Based on Generalized Pseudo Zernike Moment and Ada-DEWNN Classifier. AB - In this paper, a novel framework of computer-aided diagnosis (CAD) system has been presented for the classification of benign/malignant breast tissues. The properties of the generalized pseudo-Zernike moments (GPZM) and pseudo-Zernike moments (PZM) are utilized as suitable texture descriptors of the suspicious region in the mammogram. An improved classifier- adaptive differential evolution wavelet neural network (Ada-DEWNN) is proposed to improve the classification accuracy of the CAD system. The efficiency of the proposed system is tested on mammograms from the Mammographic Image Analysis Society (mini-MIAS) database using the leave-one-out cross validation as well as on mammograms from the Digital Database for Screening Mammography (DDSM) database using 10-fold cross validation. The proposed method on MIAS-database attains a fair accuracy of 0.8938 and AUC of 0.935 (95 % CI = 0.8213-0.9831). The proposed method is also tested for in-plane rotation and found to be highly rotation invariant. In addition, the proposed classifier is tested and compared with some well-known existing methods using receiver operating characteristic (ROC) analysis using DDSM- database. It is concluded the proposed classifier has better area under the curve (AUC) (0.9289) and highly precised with 95 % CI, 0.8216 to 0.9834 and 0.0384 standard error. PMID- 26892456 TI - Computational Diffusion Magnetic Resonance Imaging Based on Time-Dependent Bloch NMR Flow Equation and Bessel Functions. AB - Magnetic resonance imaging (MRI) uses a powerful magnetic field along with radio waves and a computer to produce highly detailed "slice-by-slice" pictures of virtually all internal structures of matter. The results enable physicians to examine parts of the body in minute detail and identify diseases in ways that are not possible with other techniques. For example, MRI is one of the few imaging tools that can see through bones, making it an excellent tool for examining the brain and other soft tissues. Pulsed-field gradient experiments provide a straightforward means of obtaining information on the translational motion of nuclear spins. However, the interpretation of the data is complicated by the effects of restricting geometries as in the case of most cancerous tissues and the mathematical concept required to account for this becomes very difficult. Most diffusion magnetic resonance techniques are based on the Stejskal-Tanner formulation usually derived from the Bloch-Torrey partial differential equation by including additional terms to accommodate the diffusion effect. Despite the early success of this technique, it has been shown that it has important limitations, the most of which occurs when there is orientation heterogeneity of the fibers in the voxel of interest (VOI). Overcoming this difficulty requires the specification of diffusion coefficients as function of spatial coordinate(s) and such a phenomenon is an indication of non-uniform compartmental conditions which can be analyzed accurately by solving the time-dependent Bloch NMR flow equation analytically. In this study, a mathematical formulation of magnetic resonance flow sequence in restricted geometry is developed based on a general second order partial differential equation derived directly from the fundamental Bloch NMR flow equations. The NMR signal is obtained completely in terms of NMR experimental parameters. The process is described based on Bessel functions and properties that can make it possible to distinguish cancerous cells from normal cells. A typical example of liver distinguished from gray matter, white matter and kidney is demonstrated. Bessel functions and properties are specifically needed to show the direct effect of the instantaneous velocity on the NMR signal originating from normal and abnormal tissues. PMID- 26892457 TI - Systemic lupus erythematosus presenting with mixed-type fulminant autoimmune hemolytic anemia. AB - We report the case of a 9-year-old girl who presented with mixed-type fulminant autoimmune hemolytic anemia (AIHA) at the onset of systemic lupus erythematosus (SLE). On admission, laboratory investigations indicated very severe anemia (Hb, 2.7 g/dL) with reticulocytosis and positive direct/indirect Coombs tests. In addition, agglutinative reaction was clinically observed. Based on further examinations, the patient was diagnosed with AIHA complicated with SLE, and mixed type AIHA was clinically identified. With oral prednisolone and methylprednisolone pulse therapy, the patient entered remission. PMID- 26892458 TI - Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis. AB - Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection. In this study, primary human skeletal muscle myoblasts (HSMM) were established as a novel human primary cell line that is highly permissive to CHIKV infection, with maximal amounts of infectious virions observed at 16 hours post infection. Genome-wide microarray profiling analyses were subsequently performed to identify and map genes that are differentially expressed upon CHIKV infection. Infection of HSMM cells with CHIKV resulted in altered expressions of host genes involved in skeletal- and muscular associated disorders, innate immune responses, cellular growth and death, host metabolism and virus replication. Together, this study has shown the establishment of a clinically relevant primary human cell model that paves the way for the further analysis of host factors and their involvement in the various stages of CHIKV replication cycle and viral pathogenesis. PMID- 26892460 TI - Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways. AB - Notoginsenoside R1 (NGR1) is a phytoestrogen that is isolated from Panax notoginseng It is used in China to treat many diseases, including hypoxic ischemic encephalopathy (HIE), and it has been shown to target estrogen receptors. Endoplasmic reticulum (ER) stress plays an important role in the development of cell apoptosis during ischemia, and ER stress is known to be regulated by estrogen; however, the neuroprotective mechanisms of NGR1 in neonatal HIE is unclear. In this study, oxygen-glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL), followed by exposure to a hypoxic environment in 7-day-old postnatal Sprague-Dawley rats were used to mimic HIE episodes. Potential neuroprotective effects of NGR1 against neonatal HIE and its mechanisms were examined. After HIE conditions in vitro and in vivo, we administered NGR1 or the estrogen receptor inhibitor ICI-182780 and measured cell apoptosis, brain injury by MTT assay, TTC stain, and so forth. Expression of estrogen receptors alpha (ERalpha) and beta (ERbeta), ER stress-associated proteins was detected by Western blot upon stimulation with HIE, NGR1, or ICI-182780. Results showed that after HIE, ER chaperone GRP78 was activated, ER stress-associated proapoptotic proteins (CHOP, PERK, ERO1-alpha, and IRE1alpha) were increased, caspase-12 was increased, and BCL-2 was decreased. The ER stress response and neuronal apoptosis were attenuated by NGR1 treatment. However, neuroprotective properties of NGR1 against HIE-induced apoptosis and ER stress were attenuated by ICI-182780. These results suggest that NGR1 may be an effective treatment of HIE by reducing ER stress-induced neuronal apoptosis and brain injury via estrogen receptors. PMID- 26892459 TI - Experimental transfusion-induced Babesia microti infection: dynamics of parasitemia and immune responses in a rhesus macaque model. AB - BACKGROUND: Babesiosis is an emerging tick-borne infection in humans. The increasing numbers of reported cases of transfusion-associated babesiosis (TAB), primarily caused by Babesia microti, represents a concern for the safety of the US blood supply. STUDY DESIGN AND METHODS: This study investigated kinetics of parasitemia and innate immune responses and dynamics of antibody responses during B. microti infection in rhesus macaques (RMs) using blood smears, quantitative polymerase chain reaction (qPCR), flow cytometry, and indirect fluorescent antibody testing. A total of six monkeys were transfused with either hamster or monkey-passaged B. microti-infected red blood cells (two and four monkeys, respectively) simulating TAB. RESULTS: The prepatent period in monkeys inoculated with hamster-passaged B. microti was 35 days compared with 4 days in monkeys transfused with monkey-passaged B. microti; the latter monkeys also had markedly higher parasitemia levels. The duration of the window period from the first detected parasitemia by qPCR analysis to the first detected antibody response ranged from 10 to 17 days. Antibody responses fluctuated during the course of the infection. Innate responses assessed by the frequencies of monocytes and activated B cells correlated with the kinetics and magnitude of parasitemia. On Day 14, additional activation peaks were noted for CD14+CD16+ and CD14-CD16+ monocytes and for CD11c+ myeloid dendritic cells, but only in animals transfused with monkey-passaged B. microti. Parasitemia persisted in these immunocompetent animals, similar to human infection. CONCLUSION: The results suggest that transfusion-associated transmission of B. microti leads to rapid onset of parasitemia (Day 4) in RMs, detectable antibody response 14 days later, and persistent parasitemia. PMID- 26892462 TI - Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue. AB - Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals, and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid beta-oxidation in liver and lipolysis in adipose tissue, and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system. PMID- 26892464 TI - Note of clarification regarding data on the association between the interleukin 1beta -511C>T polymorphism and breast cancer risk. PMID- 26892461 TI - Insulin resistance, endothelial function, angiogenic factors and clinical outcome in non-diabetic patients with chest pain without myocardial perfusion defects. AB - BACKGROUND: Patients with angina-like symptoms without myocardial perfusion scintigram (MPS)-verified abnormality may still be at risk for cardiovascular events. We hypothesized that insulin resistance could play a role in this population even without diagnosed diabetes. We further explored physiological and blood biomarkers, as well as global gene expression patterns that could be closely related to impaired glucose homeostasis to deepen our mechanistic understanding. METHODS: A total of 365 non-diabetic patients with suspected myocardial ischemia referred to MPS were enrolled and followed up regarding event free survival with a median time of 5.1 years. All patients underwent endothelial function assessment by reactive hyperemic index (RHI) using EndoPAT and extensive biomarker analysis. Whole blood global gene expression pathway analysis was performed in a subset of patients. RESULTS: Homeostasis model assessment of insulin resistance (HOMA-IR) added independent prognostic value in patients without myocardial perfusion defects. In a multivariable analysis, HOMA-IR was inversely associated with low RHI. Furthermore, elevated HOMA-IR was associated with decreased levels of vascular endothelial growth factor D, stem cell factor and endocan as well as to increased level of interleukin-6. Global gene expression pathway analysis of whole blood cells showed that high HOMA-IR and impaired endothelial function were associated with upregulated pro-inflammatory pathways and down-regulated eukaryotic initiation factor-2 pathway. CONCLUSIONS: Insulin resistance measured by HOMA-IR is associated with endothelial dysfunction and confers independent prognostic information in non-diabetic patients with chest pain without myocardial perfusion defects. Increased systemic pro inflammatory state and decreased levels of pro-angiogenic vascular growth factors may be important underlying molecular mechanisms. PMID- 26892463 TI - Id4 functions downstream of Bmp signaling to restrict TCF function in endocardial cells during atrioventricular valve development. AB - The atrioventricular canal (AVC) connects the atrial and ventricular chambers of the heart and its formation is critical for the development of the cardiac valves, chamber septation and formation of the cardiac conduction system. Consequently, problems in AVC formation can lead to congenital defects ranging from cardiac arrhythmia to incomplete cardiac septation. While our knowledge about early heart tube formation is relatively comprehensive, much remains to be investigated about the genes that regulate AVC formation. Here we identify a new role for the basic helix-loop-helix factor Id4 in zebrafish AVC valve development and function. id4 is first expressed in the AVC endocardium and later becomes more highly expressed in the atrial chamber. TALEN induced inactivation of id4 causes retrograde blood flow at the AV canal under heat induced stress conditions, indicating defects in AV valve function. At the molecular level, we found that id4 inactivation causes misexpression of several genes important for AVC and AV valve formation including bmp4 and spp1. We further show that id4 appears to control the number of endocardial cells that contribute to the AV valves by regulating Wnt signaling in the developing AVC endocardium. PMID- 26892466 TI - Electrophysiological findings after surgical thoracoscopic atrial fibrillation ablation. AB - BACKGROUND: Hybrid ablation (a combination of thoracoscopic epicardial ablation and catheter ablation) has become a new technique for atrial fibrillation treatment. OBJECTIVE: The goal of this study was to evaluate the success and electrophysiological follow-up after using the COBRA Fusion device to deliver a circumferential lesion set anterior to the pulmonary veins in an attempt to isolate the posterior left atrium (box isolation). METHODS: Surgical ablation was carried out via a thoracoscopic approach using the COBRA Fusion radiofrequency catheter. An electrophysiology study was done 2-3 months later to verify box isolation (and to complete it, if needed) and to perform right-sided isthmus ablation. Fat thickness along the presumed box lesion line was measured using preprocedural computed tomography. RESULTS: Thirty patients (mean age 60.0 +/- 11.6 years; 22 men; 8 with long-standing persistent AF and 22 with persistent atrial fibrillation) were enrolled. The duration of the EP study was 216.3 +/- 64.2 minutes. Box isolation, based on the EP study, was complete in 12 patients (40%) and incomplete in 18 patients (60%). Successful box isolation was achieved with catheter ablation in 16 of 18 patients (89%). A total of 39 gaps in these 16 patients were identified. Typical gap locations were the anterior-superior part of the superior pulmonary veins and the roofline. Fat thickness along the roofline was substantially higher than that along the inferior line (4.58 +/- 1.61 mm vs 2.37 +/- 0.76 mm; P < .001). CONCLUSION: There is a relatively low rate of complete isolation using the COBRA catheter ablation system. The superior line and anterior parts of superior pulmonary veins have most conduction gaps. PMID- 26892465 TI - Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia. AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR) inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK) down-regulation in the treatment of ALL. METHODS: The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mouse model. RESULTS: When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA) to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2) gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. CONCLUSIONS: FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel and powerful strategy for treating ALL. PMID- 26892468 TI - Long noncoding RNA AFAP1-AS1 indicates a poor prognosis of hepatocellular carcinoma and promotes cell proliferation and invasion via upregulation of the RhoA/Rac2 signaling. AB - It has been shown that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes including cancer progression and metastasis. However, the biological functions and clinical significance of lncRNA AFAP1-AS1 in hepatocellular carcinoma (HCC) remain unclear. Expression of AFAP1-AS1 was analyzed in 78 HCC tissues by real-time PCR. The effect of AFAP1-AS1 on cell proliferation was examined by MTT assay, cell apoptosis was detected by flow cytometric analysis and cell invasion was determined by Transwell assay. RhoA/Rac2 signaling and downstream factors were verified by western blotting. HCC cells infected with si-AFAP1-AS1 were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. We found that increased expression of AFAP1-AS1 was significantly correlated with pathological staging (P=0.024) and lymph-vascular space invasion (LVSI) in HCC patients (P=0.007). Multivariate analyses indicated that AFAP1-AS1 represented an independent predictor for overall survival of HCC (P=0.029). Further experiments showed that knockdown of AFAP1-AS1 by si-AFAP1-AS1 decreased the proliferation and invasion in vitro and in vivo, induced cell apoptosis and blocked cell cycle in S phase via inhibition of the RhoA/Rac2 signaling. Taken together, our findings indicate that AFAP1-AS1 may promote the HCC development through upregulation of RhoA/Rac2 signaling and provide a potential therapeutic target for HCC. PMID- 26892467 TI - Thyroid gland rupture caused by blunt trauma to the neck. AB - BACKGROUND: Thyroid rupture following blunt trauma is extremely rare, and neck pain without swelling may be the only presenting symptom. However, hemorrhage and hematoma subsequently causes severe tracheal compression and respiratory distress. CASE PRESENTATION: A 71-year-old Japanese woman visited our emergency room with a complaint of increasing right-sided neck pain at the thyroid cartilage level after she tripped and accidentally hit her neck against a pole 3 h back. On admission, her vital signs were stable. There was no swelling or subcutaneous emphysema. Laryngeal endoscopy revealed mild laryngeal edema, although there was no impairment in vocal fold mobility on either side. Contrast enhanced computed tomography (CT) revealed rupture of the right lobe of the thyroid gland accompanied by a large hematoma extending from the neck to the mediastinum. Under general anesthesia, the right lobe was resected and the hematoma was evacuated. CONCLUSION: Only a few isolated cases of thyroid rupture caused by blunt neck trauma have been reported in patients with normal thyroid glands and neck pain without swelling may be the only presenting symptom. When suspected, CT should be performed to confirm the diagnosis determine the optimal treatment. PMID- 26892469 TI - Characteristics of neonatal near miss in hospitals in Benin, Burkina Faso and Morocco in 2012-2013. AB - OBJECTIVE: The objective of this study is to explore the usefulness of neonatal near miss in low- and middle-income countries by examining the incidence of neonatal near miss and pre-discharge neonatal deaths across various obstetric risk categories in 17 hospitals in Benin, Burkina Faso and Morocco. METHODS: Data were collected on all maternal deaths, maternal near miss, neonatal near miss (based on organ-dysfunction markers), Caesarean sections, stillbirths, neonatal deaths before discharge and non-cephalic presentations, and on a sample of births not falling in any of the above categories. RESULTS: The burden of stillbirth, pre-discharge neonatal death or neonatal near miss ranged from 23 to 129 per 1000 births in Moroccan and Beninese hospitals, respectively. Perinatal deaths (range 17-89 per 1000 births) were more common than neonatal near miss (range 6-43 per 1000 live births), and between a fifth and a third of women who had suffered a maternal near miss lost their baby. Pre-discharge neonatal deaths and neonatal near miss had a similar distribution of markers of organ dysfunction, but unlike pre-discharge neonatal deaths most neonatal near miss (63%, 81% and 71% in Benin, Burkina Faso and Morocco, respectively) occurred among babies who were not considered premature, low birthweight or with a low 5-min Apgar score as defined by WHO's pragmatic markers of severe neonatal morbidity. CONCLUSION: Whether the measurement of neonatal near miss adds useful insights into the quality of perinatal or newborn care in settings where facility-based intrapartum and early newborn mortality is very high is uncertain. Perhaps the greatest advantage of adding near miss is the shift in focus from failure to success so that lessons can be learned on how to save lives even when clinical conditions are life threatening. PMID- 26892471 TI - Prevalence and imaging characteristics of palatine tonsilloliths evaluated on 2244 pairs of panoramic radiographs and CT images. AB - OBJECTIVES: Palatine tonsilloliths incidentally detected on diagnostic imaging should be differentiated from pathologic calcifications to enable correct diagnosis and treatment. The aim of this study is to clarify the prevalence and imaging characteristics of palatine tonsilloliths on panoramic radiographs. MATERIALS AND METHODS: We retrospectively reviewed 2244 individuals who underwent pairs of consecutive panoramic radiography and computed tomography (CT) of the head and neck region. The imaging characteristics of palatine tonsilloliths on panoramic radiography were compared with the findings from CT, which was considered the gold standard. RESULTS: Tonsilloliths were detected in 300 (13.4 %) and 914 (40.7 %) of the 2244 individuals on panoramic radiographs and CT, respectively. On panoramic radiographs, tonsilloliths were superimposed over the ramus of the mandible at the level coincident with and inferior to the soft palate in 176 (7.8 %) and 90 (4.0 %) individuals, respectively. Tonsilloliths were also superimposed over the surrounding soft tissue inferior to the body of the mandible, postero-inferior to the angle of the mandible, and posterior to the ramus of the mandible in 33 (1.5 %), 26 (1.2 %), and 28 (1.3 %) individuals, respectively. A significant correlation was observed between the detectability on panoramic radiographs and the size (Spearman r = 1.000) and number (Spearman r = 0.991) of tonsilloliths, as revealed by CT images. CONCLUSIONS: The present results suggest that tonsilloliths are commonly detected on panoramic radiographs. Furthermore, they can be superimposed on both the mandible and the surrounding soft tissue. CLINICAL RELEVANCE: Clinicians should include tonsilloliths among the differential diagnoses when calcified bodies are detected on panoramic radiographs. PMID- 26892473 TI - Vitamin B supplementation for diabetic peripheral neuropathy. AB - Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction. PMID- 26892474 TI - Exudative Polymorphous Vitelliform Retinopathy: Importance of Early Recognition of the Condition in Patients with Metastatic Melanoma. AB - INTRODUCTION: Because of the advent of monoclonal antibodies in the treatment of metastatic melanoma, patients with this disease are surviving longer. Early recognition of the disease has therefore become even more important. CASE REPORT: We present a patient with vitelliform maculopathy, a paraneoplastic retinal maculopathy that is under-recognized. Clinically the retinal findings of serous detachments and pigmentary macular changes are remarkable, while at the same time these patients have surprisingly very few symptoms. This is in contrast to patients who develop melanoma associated retinopathy (MAR) who are very symptomatic early in the disease, but with more subtle retinal findings. CONCLUSION: Monoclonal antibody treatment is changing the survival rates in metastatic disease making early diagnosis even more important. Exudative polymorphous vitelliform maculopathy (EPVM) needs to be recognized early to avoid delay in diagnosis of metastatic disease. PMID- 26892475 TI - All BMJ research papers should share their analytic code. PMID- 26892472 TI - In vitro antibacterial and remineralizing effect of adhesive containing triazine and niobium pentoxide phosphate inverted glass. AB - OBJECTIVES: White spot lesions are still a concern for orthodontic patients. The objective of this study was to assess the remineralizing and antibacterial effect of a newly developed orthodontic adhesive. METHODS: The compounds 1,3,5 tryacryloylhexahydro-1,3,5-triazine (TAT) and phosphate invert glass containing 10 mol% of niobium pentoxide (PIG-Nb) were added at 20 and 5 wt%, respectively, to an experimental adhesive (75 wt% BisGMA, 25 wt% TEGDMA, 5 wt% fummed silica, and photo-initiator system), called TPN. A group without the addition of these compounds was used as Control and the orthodontic adhesive Transbond XT (TXT) was used for comparison. Antibacterial activity was evaluated through surface biofilm formation, mineral deposition, and degree of conversion (DC) through Raman microscopy, Knoop hardness after softening in solvent, and bracket dislodgement (BD). RESULTS: TPN group presented a reduction in bacterial growth when compared to Control and TXT. Mineral deposits were observed on the surface of TPN adhesive after 14 and 28 days of immersion in artificial saliva. There was an increase in DC after 28 days, whereas TPN group presented the highest DC. All groups underwent some degree of softening. No significant changes were observed in BD after 28 days of immersion in artificial saliva. CONCLUSION: The newly developed orthodontic adhesive, with addition of 20 wt% TAT and 5w% PIG-Nb, exhibited antibacterial activity and was capable to induce mineral deposition on its surface in vitro. CLINICAL SIGNIFICANCE: The orthodontic adhesive developed in this study with antibacterial activity and mineral deposition could be a reliable choice for brackets adhesion. PMID- 26892476 TI - Is effective a prior multiparametric magnetic resonance scan in patients candidates to prostate biopsy? CAT Study. AB - We carried out a critically appraised topic (CAT)-type study to determine whether the relevant scientific evidence supports the recommendation of doing a multiparametric magnetic resonance imaging study of the prostate in all patients who are candidates for prostate biopsy with the aim of improving the detection of clinically significant prostate cancer and stratifying patients to receive active surveillance or treatment. After a formal literature search and an analysis of the two most relevant articles it found, we reached the conclusion that, despite promising results that point to the potential usefulness of this approach, there is still not enough clear scientific evidence to endorse it categorically. Before this approach can be endorsed, we need evidence from well-designed prospective randomized trials using widely agreed upon criteria and including large numbers of patients at multiple centers. PMID- 26892477 TI - Molecular Genotyping of HIV-1 Strains from Newly Infected Men Who Have Sex with Men in Harbin, China. AB - In this study, blood samples from newly HIV-1 infected men who have sex with men (MSM) were collected, and HIV-1 genotypes were identified based on gag p17-p24 and nef gene regions. We found that participants aged from 20 to 40 years old were the major infection group in Harbin. CRF01_AE was the predominant genotype, contributing to 84.7% of HIV-1 infections, followed by subtype B (4.7%), CRF07_BC (3.5%), and subtype B' (Thai B, 1.2%). Moreover, five unique recombinant forms (5.9%) were also identified, including genotypes 01B, 01C, and 01/02. The recombinant CRF01_AE/CRF02_AG was first reported in China. These results suggested that current HIV-1 genotype epidemic among MSM in Harbin is more complicated and that intersubtype recombinants have emerged. Therefore, timely regional epidemiological surveillance of HIV-1 genotype and development of prevention measures for new HIV-1 infections among MSM are quite important. PMID- 26892478 TI - 5-HT7 Receptors Are Not Involved in Neuropeptide Release in Primary Cultured Rat Trigeminal Ganglion Neurons. AB - Migraine is a common but complex neurological disorder. Its precise mechanisms are not fully understood. Increasing indirect evidence indicates that 5-HT7 receptors may be involved; however, their role remains unknown. Our previous in vivo study showed that selective blockade of 5-HT7 receptors caused decreased serum levels of calcitonin gene-related peptide (CGRP) in the external jugular vein following electrical stimulation of the trigeminal ganglion (TG) in an animal model of migraine. In the present study, we used an in vitro model of cultured TG cells to further investigate whether 5-HT7 receptors are directly responsible for the release of CGRP and substance P from TG neurons. We stimulated rat primary cultured TG neurons with capsaicin or potassium chloride (KCl) to mimic neurogenic inflammation, resulting in release of CGRP and substance P. 5-HT7 receptors were abundantly expressed in TG neurons. Greater than 93 % of 5-HT7 receptor-positive neurons co-expressed CGRP and 56 % co expressed substance P. Both the capsaicin- and KCl-induced release of CGRP and substance P were unaffected by pretreatment of cultured TG cells with the selective 5-HT7 receptor agonist AS19 and antagonist SB269970. This study demonstrates for the first time that 5-HT7 receptors are abundantly co-expressed with CGRP and substance P in rat primary TG neurons and suggests that they are not responsible for the release of CGRP and substance P from cultured TG neurons evoked by capsaicin or KCl. PMID- 26892480 TI - Three cases of pigmented cosmetic dermatitis-like eruptions associated with primary Sjogren's syndrome or anti-SSA antibody. AB - Pigmented cosmetic dermatitis-like (Riehl's melanosis-like) pigmentation was reported in three of 27 patients with primary Sjogren's syndrome. But case reports of such eruptions are rare. We describe three cases of such eruptions associated with primary Sjogren's syndrome or anti-SSA antibody and possible associations with specific types of human leukocyte antigen (HLA) and infiltrating lymphocytes. These middle-aged Japanese women had reticular facial pigmentation and histopathological examination revealed interface dermatitis, melanophages, and dense lymphocytic infiltration around hair follicles and sweat ducts. HLA typing revealed common antigenic equivalents or genetic typing of HLA A2, DR52, DPA1(02:02) and DPB1(05:01). Immunohistochemical staining revealed major subsets of T cells to be CD8 and CD45RO. Some Foxp3- and few IL17-positive cells were found in strong contrast to the major CD4 subset of infiltrated T cells in annular erythema associated with Sjogren's syndrome. Apparently, our patients' pigmentation represented a specific etiology associated with primary Sjogren's syndrome or anti-SSA antibody. PMID- 26892479 TI - Clinical impact of ABL1 kinase domain mutations and IKZF1 deletion in adults under age 60 with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL): molecular analysis of CALGB (Alliance) 10001 and 9665. AB - Recent studies have identified oncogenic lesions in Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and ABL1 kinase mutations that confer resistance to tyrosine kinase inhibitors. We sought to determine the prevalence and clinical impact of these lesions in patients on CALGB 10001, a previously reported Phase II study of imatinib, chemotherapy, and hematopoietic cell transplant in adult Ph + ALL. Of the 58 enrolled, 22 relapsed. By direct sequencing, an ABL1 kinase mutation known to induce imatinib resistance was present at relapse in 13 of 20. Using quantitative PCR assays, the mutations were detectable at diagnosis or early during treatment in most (62%) relapsed patients. Aberrations in IKZF1, CDKN2A/B, and PAX5 were assessed in 28 samples using SNP arrays and genomic DNA sequencing. Of these, 22 (79%) had IKZF1 deletion. The combination of IKZF1 deletion and p210 BCR-ABL1 (p < 0.0001), high white blood cell count (p = 0.021), and minimal residual disease (p = 0.013) were associated with worse disease-free survival. PMID- 26892481 TI - Group-sequential three-arm noninferiority clinical trial designs. AB - We discuss group-sequential three-arm noninferiority clinical trial designs that include active and placebo controls for evaluating both assay sensitivity and noninferiority. We extend two existing approaches, the fixed margin and fraction approaches, into a group-sequential setting with two decision-making frameworks. We investigate the operating characteristics including power, Type I error rate, maximum, and expected sample sizes, as design factors vary. In addition, we discuss sample size recalculation and its impact on the power and Type I error rate via a simulation study. PMID- 26892482 TI - Supramolecular polymerisation in water; elucidating the role of hydrophobic and hydrogen-bond interactions. AB - Understanding the self-assembly of small molecules in water is crucial for the development of responsive, biocompatible soft materials. Here, a family of benzene-1,3,5-tricarboxamide (BTA) derivatives that comprise a BTA moiety connected to an amphiphilic chain is synthesised with the aim to elucidate the role of hydrophobic and hydrogen-bonding interactions in the self-assembly of these BTAs. The amphiphilic chain consists of an alkyl chain with a length of 10, 11, or 12 methylene units, connected to a tetraethylene glycol (at the periphery). The results show that an undecyl spacer is the minimum length required for these BTAs to self-assemble into supramolecular polymers. Interestingly, exchange studies reveal only minor differences in exchange rates between BTAs containing undecyl or dodecyl spacers. Additionally, IR spectroscopy provides the first experimental evidence that hydrogen-bonding is operative and contributes to the stabilisation of the supramolecular polymers in water. PMID- 26892483 TI - Is Turkish MEFV Mutations Spectrum Different Among Regions? AB - BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive inherited inflammatory disease. The gene responsible for the disease, called MEFV, encodes a protein called pyrin or marenostrin. According to recent data, MEFV mutations are not the only cause of FMF, but genetic analysis of MEFV gene is needed for confirming the diagnosis of FMF. In the present study, we aimed to evaluate the molecular testing results of MEFV mutations. METHODS: Molecular testing results of 1,435 patients were retrospectively evaluated over the last 4 years. These patients were identified as having FMF clinical symptoms. Patients were tested for 12 common mutations in the MEFV gene using a strip assay technique. RESULTS: From all 1,435 patients, MEFV mutations were found in 776 patients (54.08%) and 659 patients (45.92%) did not carry any mutations. Patients with mutations were classified as homozygotes (n = 148), compound heterozygotes (n = 197), heterozygous (n = 427), and complex genotypes (n = 4, patients with three mutations). Allelic frequencies for the four most common mutations in the mutation-positive groups were 48.79% (M694V), 14.86% (M680I G/C), 13.70% (E148Q), and 12.35% (V726A). The remaining alleles (10.3%) showed rare mutations that were R761H, P369S, A744S, K695R, F479L, and M694I. No patient showed a I692del mutation that is sometimes evident in other Mediterranean populations. CONCLUSION: It was found that the most common four mutations (M694V, M680I [G/C], E148Q, V726A) were similar to those previously reported from different regions of Turkey and this study might add some knowledge to the mutational spectrum data on FMF. PMID- 26892484 TI - Electrophysiological findings in Rasmussen's syndrome. AB - Rasmussen syndrome is a rare, inflammatory and probably autoimmune disease presenting with epilepsia partialis continua which is generally in the form of myoclonic jerks and involves the upper extremities with or without head involvement. We sought to demonstrate the electrophysiological features in patients with Rasmussen syndrome. We performed continuous electrophysiological recordings of involuntary movement, as well as recordings of startle responses and long latency reflex in three patients with a diagnosis of Rasmussen syndrome. Positive and negative myoclonus were recorded. Startle responses were found to be suppressed. However, long latency reflexes were high in amplitude and one patient even had a C reflex. Stimulus-sensitive positive and negative cortical myoclonus are typical in epilepsia partialis continua of Rasmussen syndrome and degeneration of brainstem and reticulospinal pathways may develop in Rasmussen syndrome. PMID- 26892485 TI - Prevalence of different HIV-1 subtypes in sexual transmission in China: a systematic review and meta-analysis. AB - Sexual transmission has become the primary route of HIV transmission in China. Therefore, a comprehensive overview of HIV-1 subtype distribution is necessary for the prevention and control of the HIV epidemic. The present study aimed to provide a comprehensive prevalence estimate of different HIV-1 subtypes in sexual transmission in China. We conducted a systematic literature review for studies of HIV-1 subtypes in English and Chinese through several databases. Eligible articles were screened and selected by two authors independently. Random-effects model were applied to calculate the pooled prevalence of different HIV-1 subtypes, and subgroup analyses examined prevalence estimates across time, locations, and populations. A total of 130 eligible studies were identified, including 18 752 successfully genotyped samples. The pooled prevalence of CRF01_AE, subtype B, CRF07_BC, CRF08_BC, and subtype C were 44.54% (95% CI 40.81 48.30), 18.31% (95% CI 14.71-22.17), 16.45% (95% CI 13.82-19.25), 2.55% (95% CI 1.56-3.73), 0.37% (95% CI 0.11-0.72), respectively. The prevalence of subtype B in sexual transmission decreased, while the prevalence of CRF01_AE and CRF07_BC in sexual transmission, and CRF08_BC in heterosexual transmission increased. There is significant variation in HIV-1 subtype distribution between regions. The distribution of HIV-1 subtypes and circulating recombinant forms have changed significantly. The high genetic variability of HIV-1 poses a significant challenge for disease control and surveillance in China. PMID- 26892486 TI - Association of long-term blood pressure variability and brachial-ankle pulse wave velocity: a retrospective study from the APAC cohort. AB - We investigated associations between long-term blood pressure variability (BPV) and brachial-ankle pulse wave velocity (baPWV). Within the Asymptomatic Polyvascular Abnormalities Community (APAC) study, we retrospectively collected long-term BPV and baPWV measures. Long-term BPV was calculated using the mean and standard deviation of systolic blood pressure (SBP) across 4 years based on annual values of SBP. In total, 3,994 subjects (2,284 men) were eligible for inclusion in this study. We stratified the study population into four SBP quartiles. Left and right baPWV was higher in participants with long-term SBPV in the fourth quartile compared with the first quartile (left: 1,725 +/- 488 vs. 1,461 +/- 340 [p < 0.001]; right: 1,722 +/- 471 vs. 1,455 +/- 341 [p < 0.001], respectively). We obtained the same result for total baPWV (fourth vs. first quartile: 1,772 +/- 429 vs. 1,492 +/- 350 [p < 0.001]). Furthermore, there was a trend for gradually increased baPWV (>=1,400 cm/s) with increased SBPV (p < 0.001). After multivariable adjustment, baPWV was positively correlated with long term BPV (p < 0.001). In conclusion, long-term BPV is significantly associated with arterial stiffness as assessed by baPWV. PMID- 26892488 TI - Effects of selenium treatment on 6-n-propyl-2-thiouracil-induced impairment of long-term potentiation. AB - The goal of this study was to evaluate whether sodium selenite could afford protection against the effects of hypothyroidism on long-term potentiation (LTP), which is thought to be the cellular basis for learning and memory. Hypothyroidism was induced in young-adult rats by the administration of 6-n-propyl-2-thiouracil (PTU) in tap water for 21 days. Half of these hypothyroid and euthroid rats were given 10ppM selenium with their drinking water. Field potentials were recorded from the dentate gyrus in response to stimulation of the medial perforant pathway in vivo. PTU treatment resulted in a significant reduction in both free T3 and free T4 levels, whereas selenium administration to PTU-treated rats restored only the levels of free T3 to their control values. Thyroid hormone levels were not affected by selenium in euthyroid rats. PTU-treated rats exhibited an attenuation of population spike (PS) - LTP, but a comparable potentiation of excitatory postsynaptic potential (EPSP) was found among these rats. The administration of selenium to PTU-treated rats was partially able to attenuate impairment of LTP, but not of potentiation during the LTP induction protocol in hypothyroid rats. Interestingly, the hypothyroid rats that were supplemented with selenium had a lower EPSP potentiation during induction protocol than the control rats. The present study suggests a possible importance of T3 in Se-induced rescue of impaired PS-LTP in hypothyroidism. PMID- 26892487 TI - Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats. AB - Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 MUg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats. PMID- 26892489 TI - Non-blinking single-photon emitters in silica. AB - Samples for single-emitter spectroscopy are usually prepared by spin-coating a dilute solution of emitters on a microscope cover slip of silicate based glass (such as quartz). Here, we show that both borosilicate glass and quartz contain intrinsic defect colour centres that fluoresce when excited at 532 nm. In a microscope image the defect emission is indistinguishable from spin-coated emitters. The emission spectrum is characterised by multiple peaks with the main peak between 2.05 and 2.20 eV, most likely due to coupling to a silica vibration with an energy that varies between 160 and 180 meV. The defects are single-photon emitters, do not blink, and have photoluminescence lifetimes of a few nanoseconds. Photoluminescence from such defects may previously have been misinterpreted as originating from single nanocrystal quantum dots. PMID- 26892492 TI - The facile synthesis and optical waveguide properties of single-crystal 1,2,3,4,5 pentaphenyl-1,3-cyclopentadiene microrods. AB - Single-crystalline 1,2,3,4,5-pentaphenyl-1,3-cyclopentadiene (PPCP) microrods were prepared by a facile solution process. The PPCP microrods with smooth surfaces could absorb excitation light and propagate the photoluminescence (PL) emission. They showed excellent properties in the low optical loss of a single rod and feasible transfer between neighboring rods. Moreover, PPCP displayed typical aggregation-induced emission enhancement (AIEE) characteristics in the solution state. PMID- 26892491 TI - A framework for integrating thermal biology into fragmentation research. AB - Habitat fragmentation changes thermal conditions in remnant patches, and thermal conditions strongly influence organism morphology, distribution, and activity patterns. However, few studies explore temperature as a mechanism driving ecological responses to fragmentation. Here we offer a conceptual framework that integrates thermal biology into fragmentation research to better understand individual, species, community, and ecosystem-level responses to fragmentation. Specifically, the framework addresses how fragmentation changes temperature and how the effects of those temperature changes spread through the ecosystem, from organism response via thermal sensitivity, to changes in species distribution and activity patterns, to shifts in community structure following species' responses, and ultimately to changes in ecosystem functions. We place a strong emphasis on future research directions by outlining "Critical gaps" for each step of the framework. Empirical efforts to apply and test this framework promise new understanding of fragmentation's ecological consequences and new strategies for conservation in an increasingly fragmented and warmer world. PMID- 26892490 TI - Subchronic exposures to fungal bioaerosols promotes allergic pulmonary inflammation in naive mice. AB - BACKGROUND: Epidemiological surveys indicate that occupants of mold contaminated environments are at increased risk of respiratory symptoms. The immunological mechanisms associated with these responses require further characterization. OBJECTIVE: The aim of this study was to characterize the immunotoxicological outcomes following repeated inhalation of dry Aspergillus fumigatus spores aerosolized at concentrations potentially encountered in contaminated indoor environments. METHODS: Aspergillus fumigatus spores were delivered to the lungs of naive BALB/cJ mice housed in a multi-animal nose-only chamber twice a week for a period of 13 weeks. Mice were evaluated at 24 and 48 h post-exposure for histopathological changes in lung architecture, recruitment of specific immune cells to the airways, and serum antibody responses. RESULT: Germinating A. fumigatus spores were observed in lungs along with persistent fungal debris in the perivascular regions of the lungs. Repeated exposures promoted pleocellular infiltration with concomitant epithelial mucus hypersecretion, goblet cell metaplasia, subepithelial fibrosis and enhanced airway hyperreactivity. Cellular infiltration in airways was predominated by CD4(+) T cells expressing the pro allergic cytokine IL-13. Furthermore, our studies show that antifungal T cell responses (IFN-gamma(+) or IL-17A(+) ) co-expressed IL-13, revealing a novel mechanism for the dysregulated immune response to inhaled fungi. Total IgE production was augmented in animals repeatedly exposed to A. fumigatus. CONCLUSIONS & CLINICAL RELEVANCE: Repeated inhalation of fungal aerosols resulted in significant pulmonary pathology mediated by dynamic shifts in specific immune populations and their cytokines. These studies provide novel insights into the immunological mechanisms and targets that govern the health outcomes that result from repeated inhalation of fungal bioaerosols in contaminated environments. PMID- 26892493 TI - Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast. AB - Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4(+) and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z) octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast. PMID- 26892494 TI - A microanatomic abnormality of the lacrimal gland associated with Goldenhar syndrome. AB - A 12-month-old male infant, noted from birth to have a diffuse right temporal epibulbar thickening that encroached on the limbus inferotemporally, was found to manifest stigmata of Goldenhar syndrome, including a limbal dermoid with vellus hairs, esotropia, astigmatism, fullness and ectropion of the lower eyelid, preauricular skin tag, agenesis of the right kidney, and a supernumerary rib. In the excised epibulbar specimen, in addition to a solid dermoid, lobules of lacrimal gland tissue were interpreted as a portion of the palpebral or orbital lobes. This tissue displayed a unique histopathologic finding. Within some of the lobules were cuffs of eosinophilic squamous (epidermoid) cells that surrounded the intralobular ductules and made variable incursions into, with replacement of, the acinar units. Immunohistochemistry disclosed that the normal acinar and lumen forming ductular cells were intermediate weight cytokeratin7-positive. The acinar cells were additionally gross cystic disease fluid protein-15 positive. The cells of the squamous cuffs were heavy weight cytokeratin 5/6-positive. The outermost basal cells of the cuffs were cytokeratin 14-positive, in common with the myoepithelial cells of the acini. The intraacinar squamous cells were negative for smooth muscle actin and gross cystic disease fluid protein-15. These findings suggest, but do not prove, that the source of the periductular and acinar squamous metaplasia was the germinal transitional cells where the acinar myoepithelium interfaces and imperceptibly converts into ductular basal cells. The foregoing findings are evaluated in the context of the panoply of ocular, facial, and visceral anomalies manifested in Goldenhar spectrum. PMID- 26892495 TI - Interventions for hirsutism excluding laser and photoepilation therapy alone: abridged Cochrane systematic review including GRADE assessments. AB - Hirsutism is a common disorder with a major impact on quality of life. The most frequent cause is polycystic ovary syndrome. Effects of interventions (except laser and light-based therapies) were evaluated, including Grading of Recommendations Assessment, Development and Evaluation assessments. Searches included Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, Medline, Embase and five trials registers to June 2014. We included 157 randomized controlled trials (RCTs) with 10 550 participants. The majority were assessed as having a 'high risk' of bias (123 of 157). The quality of evidence was rated moderate to very low for most outcomes. Pooled data for an oral contraceptive (OCP) (ethinyl oestradiol and cyproterone acetate) compared with another OCP (ethinyl oestradiol and desogestrel) demonstrated that both treatments were effective in reducing Ferriman-Gallwey scores, but the mean difference (MD) was not statistically significant [-1.84, 95% confidence interval (CI): -3.86-0.18]. Flutamide was more effective than placebo in two studies (MD 7.60, 95% CI: -10.53 to -4.67 and MD -7.20, 95% CI: -10.15 to -4.25), as was spironolactone (MD -7.69, 95% CI: -10.12 to -5.26). Spironolactone appeared to be as effective as flutamide (two studies) and finasteride (two studies). However, finasteride and the gonadotropin-releasing analogues showed discrepant results in several RCTs. Metformin was ineffective. Cyproterone acetate combined with OCPs demonstrated greater reductions in Ferriman-Gallwey scores. Lifestyle interventions reduced body mass index but did not show improvement in hirsutism, and although cosmetic measures are frequently used, no RCTs investigating cosmetic treatments were identified. RCTs investigating OCPs in combination with antiandrogens or finasteride vs. OCP alone, or the different antiandrogens and 5alpha-reductase inhibitors are warranted. PMID- 26892496 TI - Annexin A1 Is a Physiological Modulator of Neutrophil Maturation and Recirculation Acting on the CXCR4/CXCL12 Pathway. AB - Neutrophil production and traffic in the body compartments is finely controlled, and the strong evidences support the role of CXCL12/CXCR4 pathway on neutrophil trafficking to and from the bone marrow (BM). We recently showed that the glucocorticoid-regulated protein, Annexin A1 (AnxA1) modulates neutrophil homeostasis and here we address the effects of AnxA1 on steady-state neutrophil maturation and trafficking. For this purpose, AnxA1(-/-) and Balb/C wild-type mice (WT) were donors of BM granulocytes and mesenchymal stem cells and blood neutrophils. In vivo treatments with the pharmacological AnxA1 mimetic peptide (Ac2-26) or the formyl peptide receptor (FPR) antagonist (Boc-2) were used to elucidate the pathway of AnxA1 action, and with the cytosolic glucocorticoid antagonist receptor RU 38486. Accelerated maturation of BM granulocytes was detected in AnxA1(-/-) and Boc2-treated WT mice, and was reversed by treatment with Ac2-26 in AnxA1(-/-) mice. AnxA1 and FPR2 were constitutively expressed in bone marrow granulocytes, and their expressions were reduced by treatment with RU38486. Higher numbers of CXCR4(+) neutrophils were detected in the circulation of AnxA1(-/-) or Boc2-treated WT mice, and values were rescued in Ac2-26-treated AnxA1(-/-) mice. Although circulating neutrophils of AnxA1(-/-) animals were CXCR4(+) , they presented reduced CXCL12-induced chemotaxis. Moreover, levels of CXCL12 were reduced in the bone marrow perfusate and in the mesenchymal stem cell supernatant from AnxA1(-/-) mice, and in vivo and in vitro CXCL12 expression was re-established after Ac2-26 treatment. Collectively, these data highlight AnxA1 as a novel determinant of neutrophil maturation and the mechanisms behind blood neutrophil homing to BM via the CXCL12/CXCR4 pathway. J. Cell. Physiol. 231: 2418 2427, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26892497 TI - Transient Microneedle Insertion into Hippocampus Triggers Neurogenesis and Decreases Amyloid Burden in a Mouse Model of Alzheimer's Disease. AB - Targeted microlesions of the hippocampus have been reported to enhance neurogenesis in the subgranular zone (SGZ). The potential therapeutic impact of transient insertion of a microneedle was investigated in a mouse model of Alzheimer's disease (AD). We tested the hypothesis that transient microinjury to the brain elicits cellular responses that mediate beneficial regenerative processes. Brief stereotaxic insertion and removal of a microneedle into the right hippocampus of 14-month-old APP/PS1 mouse brains resulted in (a) stimulation of hippocampal neurogenesis and (b) reduction of amyloid-beta plaque number in the CA-1 region. This treatment also resulted in a trend toward improved performance in the radial arm water maze (RAWM). Further studies of fundamental cellular mechanisms of the brain's response to microinjury will be useful for investigation of potential neuroprotective and deleterious effects of targeted microlesions and deep brain stimulation in AD. PMID- 26892500 TI - The Importance and Challenges of a Specialty-Specific National Surgical Quality Improvement Program for Head and Neck Surgery. PMID- 26892499 TI - 3D multimodal spatial fuzzy segmentation of intramuscular connective and adipose tissue from ultrashort TE MR images of calf muscle. AB - PURPOSE: To develop and evaluate an automated algorithm to segment intramuscular adipose (IMAT) and connective (IMCT) tissue from musculoskeletal MRI images acquired with a dual echo Ultrashort TE (UTE) sequence. THEORY AND METHODS: The dual echo images and calculated structure tensor images are the inputs to the multichannel fuzzy cluster mean (MCFCM) algorithm. Modifications to the basic multichannel fuzzy cluster mean include an adaptive spatial term and bias shading correction. The algorithm was tested on digital phantoms simulating IMAT/IMCT tissue under varying conditions of image noise and bias and on ten subjects with varying amounts of IMAT/IMCT. RESULTS: The MCFCM including the adaptive spatial term and bias shading correction performed better than the original MCFCM and adaptive spatial MCFCM algorithms. IMAT/IMCT was segmented from the unsmoothed simulated phantom data with a mean Dice coefficient of 0.933 +/-0.001 when contrast-to-noise (CNR) was 140 and bias was varied between 30% and 65%. The algorithm yielded accurate in vivo segmentations of IMAT/IMCT with a mean Dice coefficient of 0.977 +/-0.066. CONCLUSION: The proposed algorithm is completely automated and yielded accurate segmentation of intramuscular adipose and connective tissue in the digital phantom and in human calf data. Magn Reson Med 77:870-883, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26892501 TI - Antiresorptive treatment, when initiated after a first hip fracture, may not protect of a second contralateral episode in elderly population: A study with 685 patients. AB - INTRODUCTION: Osteoporosis predisposes for a higher risk of hip fracture and its treatment is frequently underprescribed. Our purpose was to assess the relation between having a second hip fracture and receiving osteoporosis treatment. Also to assess the relation between this second fracture and using central nervous system drugs or being institutionalised. PATIENTS AND METHODS: We reviewed all the patients that were admitted to our hospital with an osteoporotic proximal femoral fracture between September 2009 and February 2011. We identified 685 patients, 74 of which presented a contralateral fracture. We evaluated if they were receiving osteoporosis treatment or taking any medication that could affect the central nervous system and if they were institutionalised. RESULTS: A 10.8% of patients had a second fracture and the mean time between the two of them was 20 months (1-122). There was a clear female predominance (76.35%). The mean age at occurrence of the primary fracture was 83.02 years and 85 for the second. A 90.8% did not follow any type of osteoporosis medication before the first fracture. A 50.9% did not receive central nervous system drugs and 79.1% lived at home at the time of the first fracture. 12.8% of the patients that did not follow the osteoporosis treatment, had a contralateral fracture, 3% more than those that did follow some kind of treatment, but this difference was not significant (p=0.2). DISCUSSION: We identified a similar number of patients undergoing osteoporotic treatment as registered in literature. There was no significant difference between suffering a second hip fracture and following osteoporosis treatment, using psychotropic drugs or being institutionalised. PMID- 26892498 TI - SALL4, the missing link between stem cells, development and cancer. AB - There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment. This is an exciting cancer-targeting model. The major hurdle to test this model is to identify the key factors/pathway(s) within ESCs that are responsible for the cancer phenotype. SALL4 is one of few genes that can establish this link. The first publication of SALL4 is on its mutation in a human inherited disorder with multiple developmental defects. Since then, over 300 papers have been published on various aspects of this gene in stem cells, development, and cancers. This review aims to summarize our current knowledge of SALL4, including a SALL4-based approach to classify and target cancers. Many questions about this important gene still remain unanswered, specifically, on how this gene regulates cell fates at a molecular level. Understanding SALL4's molecular functions will allow development of specific targeted approaches in the future. PMID- 26892503 TI - Seizures in a Pediatric Intensive Care Unit: A Prospective Study. AB - BACKGROUND: The aim of the research is to determine the etiology and clinical features of seizures in critically ill children admitted to a pediatric intensive care unit (PICU). METHODS: A total of 203 children were admitted from June 2013 to November 2013; 45 patients were eligible. Age ranged from 2 months to 19 years. Seizures were organized as epileptic or acute symptomatic. Pediatric risk of mortality score III, Glasgow coma scale, risk factors, coexistent diagnosis, medications administered before admission, type and duration of seizures, drugs used, requirement and duration of mechanical ventilation, length of stay and neuroimaging findings were collected as demographic data prospectively. RESULTS: The male-female ratio was 0.8. Mean age was 5.4. The most common causes of seizures were acute symptomatic. Most frequent coexistent diagnosis was infectious diseases, and 53.3% had recurrent seizures. Medications were administered to 51.1% of the patients before admission. Seizures were focal in 21 (46.7%), generalized in 11 (24.4%) and 13 (28.9%) had status epilepticus. Intravenous midazolam was first-line therapy in 48.9%. Acute symptomatic seizures were usually new-onset, and duration was shorter. Epileptic seizures tended to be recurrent and were likely to progress to status epilepticus. However, type of seizures did not change severity of the disease. Also, laboratory test results, medications administered before admission, requirement and duration of ventilation, mortality and length of stay were not significant between epileptic/acute symptomatic patients. CONCLUSION: Seizures in critically ill children, which may evolve into status epilepticus, is an important condition that requires attention regardless of cause. Intensified educational programs for PICU physicians and international guidelines are necessary for a more efficient approach to children with seizures. PMID- 26892502 TI - Implementation intention and planning interventions in Health Psychology: Recommendations from the Synergy Expert Group for research and practice. AB - The current article details a position statement and recommendations for future research and practice on planning and implementation intentions in health contexts endorsed by the Synergy Expert Group. The group comprised world-leading researchers in health and social psychology and behavioural medicine who convened to discuss priority issues in planning interventions in health contexts and develop a set of recommendations for future research and practice. The expert group adopted a nominal groups approach and voting system to elicit and structure priority issues in planning interventions and implementation intentions research. Forty-two priority issues identified in initial discussions were further condensed to 18 key issues, including definitions of planning and implementation intentions and 17 priority research areas. Each issue was subjected to voting for consensus among group members and formed the basis of the position statement and recommendations. Specifically, the expert group endorsed statements and recommendations in the following areas: generic definition of planning and specific definition of implementation intentions, recommendations for better testing of mechanisms, guidance on testing the effects of moderators of planning interventions, recommendations on the social aspects of planning interventions, identification of the preconditions that moderate effectiveness of planning interventions and recommendations for research on how people use plans. PMID- 26892505 TI - Fragment-Based De Novo Design of Antimycobacterial Agents and In Vitro Potency Evaluation. AB - Tuberculosis (TB) is an infection with global impact that over time demonstrates enormously high mortality rates. The vital need for improving novel and efficient anti-TB drugs is caused by the rising rate of appearance of Multi Drug Resistant (MDR) strains to the frequently utilized drugs.In addition, the longer periods of therapy and healing, mainly in the immune compromised patients aggrevates the situation. Recent studies indicate that computer-based techniques have been used successfully in the antibacterial research. In our current approach, utilizing combined pattern of computer-based methods as fragment-based de novo design, structure-based docking and scoring, in addition to similaritybased compound searching, led to introduce seven in silico designed compounds with probable antimycobacterial properties. Then, we investigated their potency against sensitive and resistant strains of Mycobacterium sp. in vitro. Findings resulted from antimycobacterial tests and MTT assay indicated that two compounds, 1-amino 4-(phenylamino) anthracene-9,10-dione and 5-fluoroindoline-2,3-dione have useful profile and maybe good candidates for developing novel antimycobacterial drugs. PMID- 26892504 TI - Inhibition of breast cancer with transdermal tamoxifen-encapsulated lipoplex. AB - BACKGROUND: Tamoxifen is currently used for the treatment of both early and advanced estrogen receptor (ER) positive breast cancer in pre- and post menopausal women. However, using tamoxifen routinely to inhibit endogenous or exogenous estrogen effects is occasionally difficult because of its potential side effects. OBJECTIVES: The aim of this study is to design a local drug delivery system to encapsulate tamoxifen for observing their efficacy of skin penetration, drug accumulation and cancer therapy. METHODS: A cationic liposome PEG-PEI complex (LPPC) was used as a carrier for the encapsulation of tamoxifen and forming 'LPPC/TAM' for transdermal release. The cytotoxicity of LPPC/TAM was analyzed by MTT. The skin penetration, tumor growth inhibition and organ damages were measured in xenograft mice following transdermal treatment. RESULTS: LPPC/TAM had an average size less than 270 nm and a zeta-potential of approximately 40 mV. LPPC/TAM displayed dramatically increased the cytotoxic activity in all breast cancer cells, especially in ER-positive breast cancer cells. In vivo, LPPC drug delivery helped the fluorescent dye penetrating across the skim and accumulating rapidly in tumor area. Administration of LPPC/TAM by transdermal route inhibited about 86 % of tumor growth in mice bearing BT474 tumors. This local treatment of LPPC/TAM did not injury skin and any organs. CONCLUSION: LPPC-delivery system provided a better skin penetration and drug accumulation and therapeutic efficacy. Therefore, LPPC/TAM drug delivery maybe a useful transdermal tool of drugs utilization for breast cancer therapy. PMID- 26892507 TI - Accuracy of a Blood Glucose Monitoring System. PMID- 26892506 TI - Technology Use in Transition-Age Patients With Type 1 Diabetes: Reality and Promises. AB - Youth with chronic illnesses have the greatest risk for a decline in their health management during transition-age. Because of this demonstrated and well-known issue, research has focused on how to improve the transition of care process. Despite the increasing number of technological devices on the market and the advances in telemedicine modalities available to patients with type 1 diabetes (T1D), the utilization of technology is still suboptimal among patients of transition-age (ages 13-25). This article reviews the available resources, patterns of use in transition-age youth, and explores opportunities to advance technology use in transitioning patients with T1D from pediatric to adult care. PMID- 26892508 TI - Impact of acquired and innate immunity on spinal cord ischemia and reperfusion injury. AB - OBJECTIVE: The aim of this study was to clarify the impact of acquired and innate immunity on spinal cord ischemia and reperfusion injury using a mouse model of spinal cord ischemia. METHODS: To define the ischemic duration that caused paraplegia, wild-type and severe combined immunodeficiency (SCID) mice were subjected to cross-clamping of the aorta for 7, 9, 9.5, or 10.5 min with ischemic preconditioning for intestinal protection. In wild-type and SCID mice with paraplegia, histological analyses were performed to investigate viable neurons, inflammatory cells, and reactive astrocytes at 12, 24, 48, and 72 h as well as 7 days after reperfusion. RESULTS: In both wild-type and SCID mice, immediate paraplegia was induced by occlusion for 10.5 min. In both wild-type and SCID mice, no infiltration of T or B lymphocytes was observed at any point after reperfusion, but reactive astrocytes were clearly visible at 7 days after reperfusion, and the number of activated microglia peaked at 12 and 48 h after reperfusion. Although there was no significant difference, wild-type mice had a tendency to have more activated microglia than SCID mice at 12 h after reperfusion, and to have less viable neurons than SCID mice at 12, 24, 48, and 72 h after reperfusion. There was a tendency that the frequency of immediate paraplegia in wild-type mice was more than SCID mice though no statistical difference was observed. CONCLUSIONS: Innate immunity, rather than acquired immunity, may be involved in the developing immediate paraplegia in our mouse model. PMID- 26892509 TI - Effect of acute hypoxia on inspiratory muscle oxygenation during incremental inspiratory loading in healthy adults. AB - PURPOSE: To non-invasively examine the effect of acute hypoxia and inspiratory threshold loading (ITL) on inspiratory muscles [sternocleidomastoid (SCM), scalene (SA) and parasternal (PS)] oxygenation in healthy adults using near infrared spectroscopy (NIRS). METHODS: Twenty healthy adults (12 M/8 F) were randomly assigned to perform two ITL tests while breathing a normoxic or hypoxic (FIO2 = 15 %) gas mixture. NIRS devices were placed over the SCM, PS, SA, and a control muscle, tibialis anterior (TA), to monitor oxygenated (O2Hb), deoxygenated (HHb), total hemoglobin (tHb) and tissue saturation index (TSI). With the nose occluded, subjects breathed normally for 4 min through a mouthpiece that was connected to a weighted threshold loading device. ITL began by adding a 100-g weight to the ITL device. Then, every 2 min 50-g was added until task failure. Vital signs, ECG and ventilatory measures were monitored throughout the protocol. RESULT: Participants were 31 +/- 12 year and had normal spirometry. At task failure, the maximum load and ventilatory parameters did not differ between the hypoxic and normoxic ITL. At hypoxic ITL task failure, SpO2 was significantly lower, and ?HHb increased more so in SA, SCM and PS than normoxic values. SCM ?TSI decreased more so during hypoxic compared to normoxic ITL. ?tHb in the inspiratory muscles (SCM, PS and SA) increased significantly compared to the decrease in TA during both hypoxic and normoxic ITL. CONCLUSION: The SCM, an accessory inspiratory muscle was the most vulnerable to deoxygenation during incremental loading and this response was accentuated by acute hypoxia. PMID- 26892511 TI - Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis. AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. METHODS: First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. RESULTS: OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. CONCLUSION: These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. PMID- 26892513 TI - Research advances in metabolism 2015. PMID- 26892510 TI - Association of pooled cohort risk scores with vascular inflammation and coronary artery calcification in Korean adults. AB - OBJECTIVES: A new pooled cohort risk equation to estimate atherosclerotic cardiovascular disease (CVD) risk was recently published, but the equation is based primarily on data from Caucasian populations. The relationship of this new risk scoring system with vascular inflammation and calcification has yet to be examined. METHODS: A total of 74 participants were retrospectively selected based on inclusion and exclusion criteria. All participants underwent (18)F fluorodeoxyglucose (FDG) positron emission tomography (PET) and multi-detector computed tomography (MDCT) examination in the Korea University Guro Hospital between June 2009 and May 2013. Vascular inflammation of the carotid artery was measured as target-to-background ratio (TBR) using (18)F-FDG-PET/CT and coronary artery calcification was quantified as Agatston score by MDCT. RESULTS: Agatston scores were not significantly associated with any metabolic risk factors, but maximum TBR values exhibited a significant positive correlation with body mass index (r=0.31, P=0.01), waist circumference (r=0.42, P<0.01), waist-to-hip ratio (r=0.49, P<0.01), and systolic (r=0.35, P<0.01) and diastolic blood pressure (r=0.39, P<0.01). Furthermore, maximum TBR values were significantly correlated with serum high-sensitivity C-reactive protein (hsCRP) levels (r=0.26, P=0.03), whereas Agatston scores had no correlation. When pooled cohort risk equation scores were divided into incremental tertiles, age, waist circumference, waist-to hip ratio and systolic blood pressure showed significant incremental trends. In particular, pooled cohort risk scores exhibited a significant positive correlation with maximum TBR values (r=0.35, P<0.01), but not with Agatston scores (r=0.11, P=0.34). CONCLUSIONS: The pooled cohort risk equation exhibited significant positive correlations with vascular inflammation but not with calcification in Asian subjects without CVD, suggesting that this novel risk equation may detect early inflammatory changes preceding the structural modification of vessel walls. PMID- 26892512 TI - Post-prandial hypoglycemia results from a non-glucose-dependent inappropriate insulin secretion in Roux-en-Y gastric bypassed patients. AB - BACKGROUND: After Roux-en-Y gastric bypass (RYGB), hypoglycemia can occur and be associated with adverse events such as intense malaise and impaired quality of life. OBJECTIVE: To compare insulin secretion, sensitivity, and clearance between two groups of patients, with or without hypoglycemia, after an oral glucose tolerance test (OGTT 75-g), and also to compare real-life glucose profiles within these two groups. SETTING: Bariatric surgery referral center. METHODS: This study involves a prospective cohort of 46 consecutive patients who complained of malaise compatible with hypoglycemia after RYGB, in whom an OGTT 75-g was performed. A plasma glucose value of lower than 2.8 mmol/L (50 mg/dl) between 90 and 120 min after the load was considered to be a significant hypoglycemia. The main outcome measures were insulin sensitivity, beta-cell function, and glycemic profiles during the test. Glucose parameters were also evaluated by continuous glucose monitoring (CGM) in a real-life setting in 43 patients. RESULTS: Twenty five patients had plasma glucose that was lower than 2.8 mmol/L between 90 and 120 from the load (HYPO group). Twenty-one had plasma glucose that was higher than 2.8 mmol/L (NONHYPO group). The HYPO patients were younger, had lost more weight after RYGB, were less frequently diabetic before surgery, and displayed higher early insulin secretion rates compared with the NONHYPO patients after the 75-g OGTT, and they had lower late insulin secretion rates. The HYPO patients had lower interstitial glucose values in real life, which suggests that a continuum exists between observations with an oral glucose load and real-life interstitial glucose concentrations. CONCLUSIONS: This study suggests that HYPO patients after RYGB display an early increased insulin secretion rate when tested with an OGTT. CGM shows that HYPO patients spend more time below 3.3 mmol/L when compared with NONHYPO patients. This phenotype of patients should be monitored carefully after RYGB. PMID- 26892514 TI - The impact of an inverse correlation between plasma B-type natriuretic peptide levels and insulin resistance on the diabetic condition in patients with heart failure. AB - BACKGROUND: A diabetic state is causally related to heart failure (HF); therefore, there should be a close correlation between the severity of diabetes and HF. However, a direct relationship between these conditions has rarely been reported and remains unclear. This study was designed to precisely examine this relationship, taking into consideration the possible association between natriuretic peptide (NP) levels and insulin resistance. MATERIAL AND METHODS: We examined various hemodynamic parameters and simultaneously performed blood biochemical analyses of consecutive patients who underwent cardiac catheterization at our institution (n=840). RESULTS: Simple regression analyses showed that hemoglobin A1c (HbA1c) levels were not significantly changed by the left ventricular end-diastolic pressure (LVEDP) and left ventricular ejection fraction (LVEF), which were correlated with a low cardiac index. Rather, there was a negative correlation between the HbA1c levels and plasma BNP levels as a marker of HF. A multivariate analysis showed no correlations between the HbA1c levels and cardiac functional parameters (LVEDP, LVEF or the plasma BNP levels), suggesting that the trend toward high HbA1c levels in HF cases is likely to be limited for unknown reasons. To search for an explanation of this finding, we examined the potential biological interactions between BNP and insulin resistance. A multivariate analysis revealed that the plasma BNP levels were positively correlated with age, creatinine levels and LVEDP and inversely correlated with the male gender, body mass index and HOMA-IR (homeostasis model assessment-insulin resistance) (P<0.001, respectively), but not HbA1c levels. This analysis indicated a close correlation between plasma BNP levels and insulin effectiveness in HF. CONCLUSIONS: HF and diabetes tend to worsen with each other; however, the appearance of an association between them was likely blunted due to the considerable effect of NP in counteracting insulin resistance, even during the metabolically harmful condition of HF. PMID- 26892515 TI - The genetic spectrum of familial hypercholesterolemia in south-eastern Poland. AB - BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder with a frequency of 1 in 200 to 500 in most European populations. Mutations in LDLR, APOB and PCSK9 genes are known to cause FH. In this study, we analyzed the genetic spectrum of the disease in the understudied Polish population. MATERIALS AND METHODS: 161 unrelated subjects with a clinical diagnosis of FH from the south-eastern region of Poland were recruited. High resolution melt and direct sequencing of PCR products were used to screen 18 exons of LDLR, a region of exon 26 in the APOB gene and exon 7 of PCSK9. Multiplex ligation-dependent probe amplification (MLPA) was performed to detect gross deletions and insertions in LDLR. Genotypes of six LDL-C raising SNPs were used for a polygenic gene score calculation. RESULTS: We found 39 different pathogenic mutations in the LDLR gene with 10 of them being novel. 13 (8%) individuals carried the p.Arg3527Gln mutation in APOB, and overall the detection rate was 43.4%. Of the patients where no mutation could be found, 53 (84.1%) had a gene score in the top three quartiles of the healthy comparison group suggesting that they have a polygenic cause for their high cholesterol. CONCLUSIONS: These results confirm the genetic heterogeneity of FH in Poland, which should be considered when designing a diagnostic strategy in the country. As in the UK, in the majority of patients where no mutation can be found, there is likely to be a polygenic cause of their high cholesterol level. PMID- 26892516 TI - The bile acid TUDCA increases glucose-induced insulin secretion via the cAMP/PKA pathway in pancreatic beta cells. AB - OBJECTIVE: While bile acids are important for the digestion process, they also act as signaling molecules in many tissues, including the endocrine pancreas, which expresses specific bile acid receptors that regulate several cell functions. In this study, we investigated the effects of the conjugated bile acid TUDCA on glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells. METHODS: Pancreatic islets were isolated from 90-day-old male mice. Insulin secretion was measured by radioimmunoassay, protein phosphorylation by western blot, Ca(2+) signals by fluorescence microscopy and ATP-dependent K(+) (KATP) channels by electrophysiology. RESULTS: TUDCA dose-dependently increased GSIS in fresh islets at stimulatory glucose concentrations but remained without effect at low glucose levels. This effect was not associated with changes in glucose metabolism, Ca(2+) signals or KATP channel activity; however, it was lost in the presence of a cAMP competitor or a PKA inhibitor. Additionally, PKA and CREB phosphorylation were observed after 1-hour incubation with TUDCA. The potentiation of GSIS was blunted by the Galpha stimulatory, G protein subunit specific inhibitor NF449 and mimicked by the specific TGR5 agonist INT-777, pointing to the involvement of the bile acid G protein-coupled receptor TGR5. CONCLUSION: Our data indicate that TUDCA potentiates GSIS through the cAMP/PKA pathway. PMID- 26892518 TI - Hyperuricemia induces hypertension through activation of renal epithelial sodium channel (ENaC). AB - OBJECTIVES: The mechanisms leading to hypertension associated with hyperuricemia are still unclear. The activity of the distal nephron epithelial sodium channel (ENaC) is an important determinant of sodium balance and blood pressure. Our aim was to investigate whether the effect of hyperuricemia on blood pressure is related to ENaC activation. METHODS: A hyperuricemic model was induced in rats by 2% oxonic acid and 6 mg/dl uric acid (UA). The hyperuricemic rats were co-treated with either 10mg/kg/d benzbromarone (Ben) or 1 mg/kg/d amiloride (Ami). Blood pressure was monitored using a tail-cuff, and blood, urine, and kidney samples were taken. Western blotting and immunohistochemical staining were performed to determine the expressions of ENaC subunits and components of the ENaC Regulatory Complex (ERC) in kidney tissue or mCCD cells. RESULTS: Serum uric acid (SUA) was increased 2.5-3.5 times above normal in hyperuricemic rats after 3 weeks and remained at these high levels until 6 weeks. The in vivo rise in SUA was followed by elevated blood pressure, renal tubulointerstitial injury, and increased expressions of ENaC subunits, SGK1, and GILZ1, which were prevented by Ben treatment. The decrease in urinary Na(+) excretion in hyperuricemic rats was blunted by Ami. UA induced the expression of all three ENaC subunits, SGK1, and GILZ1, and increased Na(+) transport in mCCD cells. Phosphorylation of ERK was significantly decreased in both UA-treated mCCD cells and hyperuricemic rat kidney; this effect was prevented by Ben co-treatment. CONCLUSION: Our findings suggest that elevated serum uric acid could induce hypertension by activation of ENaC and regulation of ERC expression. PMID- 26892517 TI - Circulating level of hepatocyte growth factor predicts incidence of type 2 diabetes mellitus: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - BACKGROUND: Hepatocyte growth factor (HGF) is a pleotropic factor posited to have metabolic homeostatic properties. The purpose of this study is to examine whether level of HGF is associated with the development of type 2 diabetes. METHODS: Data from the Multi-Ethnic Study of Atherosclerosis (MESA) were used to examine the prospective association between serum level of HGF and incident diabetes. Fasting HGF was measured at Exam 1 (2000-2002) in 5395 participants free from diabetes (61.5+/-10.2 years old) and incidence of diabetes was determined at four subsequent follow-up exams over 12 years. Hazard ratios (HR) for incident diabetes were estimated according to 1 standard deviation (SD) unit increment of HGF (1 SD=26 MUg/l), before and after adjustment for age, sex, race/ethnicity, education, study center, smoking status, alcohol consumption, body mass index, waist circumference, fasting glucose and insulin, C-reactive protein, and interleukin-6 levels. RESULTS: A 1 SD increment of baseline HGF was associated with a 46% (95% CI=1.37, 1.56) increased risk of diabetes before adjustment. After adjustment, diabetes risk per 1 SD increment of HGF was attenuated but remained significantly increased (HR=1.21; 95% CI=1.12, 1.32). Men had a significantly greater HR compared to women per equivalent increase of HGF (p value for sex interaction=0.04). There was no evidence of effect modification by race/ethnicity. CONCLUSIONS: This study advances understanding from cross sectional studies and investigation of incident insulin resistance, demonstrating higher level of HGF is associated with incident diabetes and may reflect a unique type of impaired metabolism. PMID- 26892519 TI - Abundance and turnover of GLP-1 producing L-cells in ileal mucosa are not different in patients with and without type 2 diabetes. AB - INTRODUCTION: The gastrointestinal hormone GLP-1 is released from enteroendocrine L-cells and augments postprandial insulin secretion. In patients with type 2 diabetes, the incretin effect is markedly diminished. It is unclear, whether this is due to a reduction in the abundance of L-cells in the intestine. METHODS: Ileal tissue samples from 10 patients with and 10 patients without diabetes that underwent surgery for the removal of colon tumors were included. Tissue sections were stained for GLP-1, Ki67, TUNEL and chromogranin A. RESULTS: The number of L cells was not different between patients with and without diabetes in either crypts (1.81+/-0.21% vs. 1.49+/-0.24%, respectively; p=0.31) or villi (1.07+/ 0.16% vs. 0.83+/-0.10%, respectively; p=0.23). L-cell number was higher in crypts than in villi (p<0.0001). L-cell replication was detected rarely and not different between the groups. L-cell apoptosis was similar in patients with and without diabetes in both crypts (7.84+/-2.77% vs. 8.65+/-3.77%, p=0.85) and villi (4.48+/-2.89% vs. 8.62+/-4.64%, p=0.42). Chromogranin A staining was found in a subset of L-cells only. CONCLUSIONS: Intestinal L-cell density is higher in crypts than in villi. Chromogranin A is not a prerequisite for GLP-1 production. L-cell density and turnover are not different between patients with and without diabetes. Thus, alterations in the number of GLP-1 producing cells do not explain the reduced incretin effect in patients with type 2 diabetes. PMID- 26892521 TI - Metabolic characteristics of keto-adapted ultra-endurance runners. AB - BACKGROUND: Many successful ultra-endurance athletes have switched from a high carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of metabolic adaptations. METHODS: Twenty elite ultra-marathoners and ironman distance triathletes performed a maximal graded exercise test and a 180 min submaximal run at 64% VO2max on a treadmill to determine metabolic responses. One group habitually consumed a traditional high carbohydrate (HC: n=10, %carbohydrate:protein:fat=59:14:25) diet, and the other a low-carbohydrate (LC; n=10, 10:19:70) diet for an average of 20 months (range 9 to 36 months). RESULTS: Peak fat oxidation was 2.3-fold higher in the LC group (1.54+/-0.18 vs 0.67+/-0.14 g/min; P=0.000) and it occurred at a higher percentage of VO2max (70.3+/-6.3 vs 54.9+/-7.8%; P=0.000). Mean fat oxidation during submaximal exercise was 59% higher in the LC group (1.21+/-0.02 vs 0.76+/ 0.11 g/min; P=0.000) corresponding to a greater relative contribution of fat (88+/-2 vs 56+/-8%; P=0.000). Despite these marked differences in fuel use between LC and HC athletes, there were no significant differences in resting muscle glycogen and the level of depletion after 180 min of running (-64% from pre-exercise) and 120 min of recovery (-36% from pre-exercise). CONCLUSION: Compared to highly trained ultra-endurance athletes consuming an HC diet, long term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar. PMID- 26892520 TI - Associations of insulin resistance, inflammation and liver synthetic function with very low-density lipoprotein: The Cardiovascular Health Study. AB - INTRODUCTION: Production of very low-density lipoprotein (VLDL) is increased in states of metabolic syndrome, leading to hypertriglyceridemia. However, metabolic syndrome is often associated with non-alcoholic fatty liver disease, which leads to liver fibrosis and inflammation that may decrease VLDL production. In this study, we aim to determine the interactive impact on VLDL profiles from insulin resistance, impairment in liver synthetic function and inflammation. METHODS: We examined cross-sectional associations of insulin sensitivity, inflammation, and liver synthetic function with VLDL particle (VLDL-P) concentration and size among 1,850 older adults in the Cardiovascular Health Study. RESULTS: Indices for high insulin sensitivity and low liver synthetic function were associated with lower concentrations of VLDL-P. In addition, insulin resistance preferentially increased concentration of large VLDL and was associated with mean VLDL size. Indices for inflammation however demonstrated a nonlinear relationship with both VLDL-P concentration and VLDL size. When mutually adjusted, one standard deviation (SD) increment in Matsuda index and C-reactive protein (CRP) were associated with 4.9 nmol/L (-8.2 to -1.5, p=0.005) and 6.3 nmol/L (-11.0 to -1.6, p=0.009) lower VLDL-P concentration respectively. In contrast, one-SD increment in factor VII, a marker for liver synthetic function, was associated with 16.9 nmol/L (12.6-21.2, p<0.001) higher VLDL-P concentration. Furthermore, a one-SD increment in the Matsuda index was associated with 1.1 nm (-2.0 to -0.3, p=0.006) smaller mean VLDL size, whereas CRP and factor VII were not associated with VLDL size. CONCLUSION: Insulin sensitivity, inflammation and markers for liver synthetic function differentially impact VLDL-P concentration and VLDL size. These results underscore the complex effects of insulin resistance and its complications on VLDL production. PMID- 26892522 TI - Abdominal obesity and circulating metabolites: A twin study approach. AB - OBJECTIVE: To investigate how obesity, insulin resistance and low-grade inflammation link to circulating metabolites, and whether the connections are due to genetic or environmental factors. SUBJECTS AND METHODS: Circulating serum metabolites were determined by proton NMR spectroscopy. Data from 1368 (531 monozygotic (MZ) and 837 dizygotic (DZ)) twins were used for bivariate twin modeling to derive the genetic (rg) and environmental (re) correlations between waist circumference (WC) and serum metabolites. Detailed examination of the associations between fat distribution (DEXA) and metabolic health (HOMA-IR, CRP) was performed among 286 twins including 33 BMI-discordant MZ pairs (intrapair BMI difference >=3 kg/m(2)). RESULTS: Fat, especially in the abdominal area (i.e. WC, android fat % and android to gynoid fat ratio), together with HOMA-IR and CRP correlated significantly with an atherogenic lipoprotein profile, higher levels of branched-chain (BCAA) and aromatic amino acids, higher levels of glycoprotein, and a more saturated fatty acid profile. In contrast, a higher proportion of gynoid to total fat associated with a favorable metabolite profile. There was a significant genetic overlap between WC and several metabolites, most strongly with phenylalanine (rg=0.40), glycoprotein (rg=0.37), serum triglycerides (rg=0.36), BCAAs (rg=0.30-0.40), HDL particle diameter (rg=-0.33) and HDL cholesterol (rg=-0.30). The effect of acquired obesity within the discordant MZ pairs was particularly strong for atherogenic lipoproteins. CONCLUSIONS: A wide range of unfavorable alterations in the serum metabolome was associated with abdominal obesity, insulin resistance and low-grade inflammation. Twin modeling and obesity-discordant twin analysis suggest that these associations are partly explained by shared genes but also reflect mechanisms independent of genetic liability. PMID- 26892524 TI - First trimester screening for gestational diabetes mellitus by maternal factors and markers of inflammation. AB - OBJECTIVE: To examine the potential role of maternal serum levels of tumor necrosis factor-alpha (TNF-alpha) and high sensitivity C-reactive protein (Hs CRP) in the first trimester of pregnancy in the prediction of gestational diabetes mellitus (GDM). METHODS: Maternal serum TNF-alpha and Hs-CRP concentrations were measured in a case-control study of singleton pregnancies at 11-13 weeks' gestation, which included 200 cases that subsequently developed GDM and 800 unaffected controls. Measured levels of TNF-alpha and Hs-CRP were expressed as multiples of the median (MoM) after adjustment for maternal characteristics and history. The performance of screening for GDM by maternal factors and MoM values of TNF-alpha and Hs-CRP was evaluated by the area under the receiver operating characteristic curves (AUROC). RESULTS: In the GDM group, compared to the normal group, the median TNF-alpha was significantly increased (1.303 MoM, interquartile range [IQR] 1.151-1.475 vs. 1.0 MoM, IQR 0.940-1.064; p=0.031) and the median Hs-CRP was not significantly different (1.113 MoM, IQR 0.990-1.250 vs. 1.0 MoM, IQR 0.943-1.060; p=0.084). In the prediction of GDM, the AUROC for maternal characteristics with TNF-alpha or Hs-CRP was not significantly different than the AUROC for maternal characteristics alone (p=0.5055 and p=0.2197, respectively). CONCLUSIONS: In pregnancies that develop GDM there is no evidence of an inflammatory response at 11-13 weeks' gestation and the levels of serum TNF-alpha and Hs-CRP are not useful in first-trimester screening for GDM. PMID- 26892523 TI - The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway. AB - INTRODUCTION: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. METHODS: The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. RESULTS: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p<0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p<0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration. PMID- 26892525 TI - A novel DPP-4 inhibitor teneligliptin scavenges hydroxyl radicals: In vitro study evaluated by electron spin resonance spectroscopy and in vivo study using DPP-4 deficient rats. AB - AIMS: Recently various dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged because of their high effectiveness and safety. In spite of their common effect of DPP-4 inhibition, the chemical structures are diverse. Here we show that the structure of teneligliptin, a novel DPP-4 inhibitor, has a scavenging activity on hydroxyl radical (.OH). METHODS: .OH and superoxide (O2(-)) were detected by electron spin resonance (ESR) spectroscopy. .OH and O2(-) were generated in vitro by the Fenton reaction and a hypoxanthine-xanthine oxidase system, respectively. The level of free radicals was estimated from the ESR signal intensity. The product via teneligliptin and .OH reaction was identified by thin layer chromatography and mass spectrometry analysis. In vivo effect was also evaluated using DPP-4 deficient rats with streptozotocin-induced diabetes. RESULTS: ESR spectroscopy analysis showed that teneligliptin did not scavenge O2(-), but scavenged .OH in a dose dependent manner. Its activity was greater than that of glutathione. The reaction product appeared to have an oxygen-atom added structure to that of teneligliptin, which was identical to the most abundant metabolite of teneligliptin in human plasma. Furthermore, using DPP-4 deficient rat, teneligliptin did not affect plasma glucose levels or body weight, but normalized increased levels of 8-hydroxy-2'-deoxyguanosine in urine, kidney and aorta of diabetic rats, supporting that teneligliptin may have a .OH scavenging activity in vivo independently of DPP-4 inhibition. CONCLUSIONS: Teneligliptin is not only effective as DPP-4 inhibitor, but may also be beneficial as .OH scavenger, which may be useful in the prevention of diabetic complications. PMID- 26892526 TI - Cerebrovascular Events After No-Touch Off-Pump Coronary Artery Bypass Grafting, Conventional Side-Clamp Off-Pump Coronary Artery Bypass, and Proximal Anastomotic Devices: A Meta-Analysis. AB - BACKGROUND: Off-pump coronary artery bypass (OPCAB) has been shown to reduce the risk of neurologic complications as compared to coronary artery bypass grafting performed with cardiopulmonary bypass. Side-clamping of the aorta while constructing proximal anastomoses, however, still carries substantial risk of cerebral embolization. We aimed to perform a comprehensive meta-analysis of studies assessing 2 clampless techniques: aortic "no-touch" and proximal anastomosis devices (PAD) for OPCAB. METHODS AND RESULTS: PubMed, CINAHL, CENTRAL, and Google Scholar databases were screened for randomized controlled trials and observational studies comparing "no-touch" and/or PAD with side-clamp OPCAB and reporting short-term (<=30 days) outcomes: cerebrovascular accident and all-cause mortality. A total of 18 studies (3 randomized controlled trials) enrolling 25 163 patients were included. Aortic "no-touch" was associated with statistically lower risk of cerebrovascular accident as compared to side-clamp OPCAB: risk ratio 95% CI: 0.41 (0.27-0.61); P<0.01; I(2)=0%. Event rates were 0.36% and 1.28% for "no-touch" and side-clamp OPCAB, respectively. No difference was seen between PAD and side-clamp OPCAB: 0.71 (0.33-1.55); P=0.39; I(2)=39%. A trend towards increased 30-day all-cause mortality with PAD and no difference with "no-touch" were observed when compared to side-clamp OPCAB. In a subset analysis, "no-touch" consistently reduced the risk of cerebrovascular accident regardless of patients' baseline risk characteristics. A benefit with PAD was observed in low-risk patients. CONCLUSIONS: Aortic "no-touch" technique was associated with nearly 60% lower risk of postoperative cerebrovascular events as compared to conventional side-clamp OPCAB with effect consistent across patients at different risk. PMID- 26892527 TI - Angiotensin-Converting Enzyme 3 (ACE3) Protects Against Pressure Overload-Induced Cardiac Hypertrophy. AB - BACKGROUND: Angiotensin-converting enzyme 3 (ACE3) is a recently defined homolog of ACE. However, the pathophysiological function of ACE3 is largely unknown. Here, we aim to explore the role of ACE3 in pathological cardiac hypertrophy. METHODS AND RESULTS: Neonatal rat cardiomyocytes (NRCMs) with gain and loss of function of ACE3 and mice with global knockout or cardiac-specific overexpression of ACE3 were used in this study. In cultured cardiomyocytes, ACE3 conferred protection against angiotensin II (Ang II)-induced hypertrophic growth. Cardiac hypertrophy in mice was induced by aortic banding (AB) and the extent of hypertrophy was analyzed through echocardiographic, pathological, and molecular analyses. Our data demonstrated that ACE3-deficient mice exhibited more pronounced cardiac hypertrophy and fibrosis and a strong decrease in cardiac contractile function, conversely, cardiac-specific ACE3-overexpressing mice displayed an attenuated hypertrophic phenotype, compared with control mice, respectively. Analyses of the underlying molecular mechanism revealed that ACE3 mediated protection against cardiac hypertrophy by suppressing the activation of mitogen-activated protein kinase kinase (MEK)-regulated extracellular signal regulated protein kinase (ERK1/2) signaling, which was further evidenced by the observation that inhibition of the MEK-ERK1/2 signaling by U0126 rescued the exacerbated hypertrophic phenotype in ACE3-deficient mice. CONCLUSIONS: Our comprehensive analyses suggest that ACE3 inhibits pressure overload-induced cardiac hypertrophy by blocking the MEK-ERK1/2 signaling pathway. PMID- 26892529 TI - Erratum to: Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes. PMID- 26892528 TI - Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Lesions. PMID- 26892532 TI - Clinicopathological study on penetrating atherosclerotic ulcers and aortic dissection: distinct pattern of development of initial event. AB - An intimal tear is responsible for the development of aortic dissection (AD). Plaque rupture is thought to progress to a penetrating atherosclerotic ulcer (PAU). However, the influences of mechanical stress and atherosclerosis on the intimal tear of AD and plaque rupture of PAU have not been fully understood. We enrolled 27 patients with AD [67.6 +/- 11.2 years, female/male (F/M) 12/15] and 10 patients with PAU (71.0 +/- 8.64 years, F/M 2/8) who underwent aortic reconstructive surgery in our hospital between 2007 and 2011. We analyzed the clinical data and morphological features of these patients and discuss the role of mechanical stress in the initial event. On clinical examination, hypertension was frequently observed in the patients of both the AD (77.8 %) and PAU groups (90.0 %), while hypercholesterolemia was significantly more prevalent in the PAU group (90.0 %) than in the AD (22.2 %) group. Most lesions of AD (96.3 %) were found in the ascending aorta up to the aortic arch, while those of PAU (90.0 %) were found in the descending and abdominal aortas. On pathological examination, the entrance tear was found in 21 (77.8 %) of the 27 patients with AD, and histologically comprised nonatherosclerotic intima and media. In contrast, the entrance tear was considered as plaque ulcer in 8 (80.0 %) of the 10 patients with PAU. The patients with PAU showed a significantly higher prevalence of soft plaque, complicated lesions, and medial fibrosis than those with AD, whereas patients with AD showed no complicated lesions and had a significantly higher prevalence of cystic medial necrosis than those with PAU. The present study suggests that less atherosclerosis and impairment of media could proceed to intimal tear formation in AD and that the disruption of the fibrous cap could cause the plaque ulcer of PAU. PMID- 26892531 TI - Renal function on admission modifies prognostic impact of diuretics in acute heart failure: a propensity score matched and interaction analysis. AB - Although intravenous diuretics have been mainstay drugs in patients with acute heart failure (AHF), they have been suggested to have some deleterious effects on prognosis. We postulated that renal function may modify their deleterious effects in AHF patients. The study population consisted of 1094 AHF patients from three hospitals. Renal dysfunction (RD) was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 on admission, and the cohort was divided into a high-dose furosemide (>=100 mg/48 h) and low-dose furosemide group according to the amount of intravenous furosemide used within 48 h from admission. In the whole cohort, in-hospital mortality rate was higher in the high-dose furosemide group than the low-dose furosemide group (12.5 vs. 6.6 %, respectively, P = 0.001). However, this difference in the in-hospital mortality rates was significant only in the RD subgroup (15.6 vs. 7.0 %, respectively, P < 0.001), and not in the non-RD subgroup (2.5 vs. 5.9 %, respectively, P = 0.384). Propensity score-matched analysis was performed to evaluate the impact of high dose furosemide on prognosis. After propensity score matching, high-dose furosemide was not associated with in-hospital mortality (OR 1.25, 95 % CI 0.73 2.16, P = 0.408). However, there was a qualitative difference in OR for in hospital mortality between AHF with RD (OR 1.77, 95 % CI 0.96-3.28, P = 0.068) and without RD (OR 0.23, 95 % CI 0.05-1.10, P = 0.064), and there was a significant interaction between eGFR and prognostic impact of high-dose furosemide (P for OR interaction = 0.013). An inverse relationship was observed between eGFR and OR for in-hospital death in the group treated with high-dose furosemide (decreasing OR with better eGFR). The deleterious effect of diuretics was significantly modified with renal function in AHF. This association may be one reason for poorer prognosis of AHF patients complicated with renal impairment. PMID- 26892530 TI - Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure. AB - Myocardial fibrosis and microvascular dysfunction are key determinants of outcome in heart failure (HF); we examined their relationship in patients with HF. Our study included 61 consecutive patients with HF but without coronary stenosis. All underwent gadolinium-enhanced cardiac magnetic resonance to evaluate late gadolinium enhancement (LGE) and an acetylcholine (ACh) provocation test to evaluate microvascular dysfunction. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations. We quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. We detected LGE in 34 patients (LGE-positive); 27 were LGE-negative. Coronary blood flow volume increased significantly after the ACh provocation test only in LGE-negative patients (before vs. after ACh, 47.5 +/- 36.8 vs. 69.2 +/- 48.0 ml/min, respectively; p = 0.004). The myocardial lactate extraction ratio (LER) significantly decreased after the ACh test in both groups (LGE-negative, p = 0.001; LGE-positive, p < 0.001), significantly more so in the LGE-positive group (p = 0.017). Multivariate logistic regression analysis showed that a post-ACh LER < 0 (indicating myocardial lactate production) was a significant predictor of LGE-positivity (odds ratio 4.54; 95 % confidence interval 1.38-14.93; p = 0.013). In the LGE-positive group, an LGE volume greater than the median significantly predicted a post-ACh LER of <0 (p = 0.042; odds ratio 6.02; 95 % confidence interval 1.07-33.86). ACh-provoked coronary vasomotor abnormality is closely correlated with myocardial fibrosis in patients with HF but without organic coronary stenosis. Coronary vasomotor abnormalities in fibrotic myocardium may worsen HF. PMID- 26892534 TI - Relation between detection rate and inappropriate shocks in single versus dual chamber cardioverter-defibrillator--an analysis from the OPTION trial. AB - The programming of implantable cardioverter-defibrillators (ICDs) influences inappropriate shock rates. The aim of the study is to analyse rates of patients with appropriate and inappropriate shocks according to detection zones in the OPTION trial. All patients received dual chamber (DC) ICDs randomly assigned to be programmed either to single chamber (SC) or to DC settings including PARAD+ algorithm. In a post-hoc analysis, rates of patients with inappropriate and appropriate shocks were calculated for shocks triggered at heart rates >= 170 bpm (ventricular tachycardia zone) and at rates >= 200 bpm (ventricular fibrillation zone). In the SC group, higher rates of patients with total and inappropriate shocks were delivered at heart rates >= 170 bpm than at rates >= 200 bpm (total shocks: 21.1% vs. 16.6%; p = 0.002; inappropriate shocks: 7.6% vs. 4.5%, p = 0.016; appropriate shocks: 15.2% vs. 13.5%; p = n.s.). No such differences were observed in the DC group (total shocks: 14.3% vs. 12.6%; p = n.s.; inappropriate shocks: 3.9% vs. 3.6%; p = n.s.; appropriate shocks: 12.2% vs. 10.4%; p = n.s.). The higher frequency of patients with total shocks with SC settings than with DC settings that benefit from PARAD+ was driven by a higher percentage of patients with inappropriate shocks in the VT zone (170-200 bpm) in the SC population. PMID- 26892533 TI - Inotropic agents use in patients hospitalized with acute decompensated heart failure: a retrospective analysis from a 22-year registry in a Middle-Eastern Country (1991-2013). AB - BACKGROUND: Data about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited. METHODS: The records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use. RESULTS: Eight hundred fifty eight patients [10.6%, 95% CI (10 to 11.3%)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0% vs. 0.9%, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6% vs. 3.2%, p = 0.001) and in-hospital mortality (30.8% vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates. CONCLUSION: Inotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study. PMID- 26892536 TI - High-level expression of Proteinase K from Tritirachium album Limber in Pichia pastoris using multi-copy expression strains. AB - Proteinase K is widely used in scientific research and industries. This report was aimed to achieve high-level expression of proteinase K using Pichia pastoris GS115 as the host strain. The coding sequence of a variant of proteinase K that has higher activity than the wild type protein was chosen and optimized based on the codon usage preference of P. pastoris. The novel open reading frame was synthesized and a series of multi-copy expression vectors were constructed based on the pHBM905BDM plasmid, allowing for the tandem integration of multiple copies of the target gene into the genome of P. pastoris with a single recombination. These strains were used to study the correlation between the gene copy number and the expression level of proteinase K. The results of quantitative polymerase chain reaction (qPCR) indicated that the tandem expression cassettes were integrated into the host genome stably. Meanwhile, the results of qPCR and enzyme activity assays indicated that the mRNA and protein expression levels of the target gene increased as the gene copy number increased. Moreover, the effect of gene dosage on the expression level of the recombinant protein was more obvious using high-density fermentation. The maximum expression level and enzyme activity of proteinase K, which were obtained from the recombinant yeast strain bearing 5 copies of the target gene after an 84-h induction, were approximately 8.069 mg/mL and 108,295 U/mL, respectively. The recombinant proteinase was purified and characterized. The optimum pH and temperature for the activity of this protease were approximately pH 11 and 55 degrees C, respectively. PMID- 26892535 TI - Purification of F plasmid-encoded native TraC from Escherichia coli by affinity chromatography on calmodulin Sepharose. AB - We have enriched several native bacterial proteins from Escherichia coli by chromatography on the immobilized eukaryotic Ca(2+)-binding protein, calmodulin. These bacterial proteins bound in a Ca(2+)-dependent manner to calmodulin, and were released by the addition of the Ca(2+)-chelator, EGTA, similar to many eukaryotic calmodulin-binding proteins. One of the bacterial proteins, F factor encoded TraC, was purified to apparent homogeneity by an additional chromatographic step, anion exchange chromatography on MonoQ. Experiments with four chemically distinct calmodulin antagonists (R24571, Compound 48/80, melittin, and W7) showed that all of these substances inhibited the binding of purified TraC to calmodulin at effective concentrations comparable to those required for inhibiting in vitro binding of eukaryotic calmodulin-binding proteins. Three further bacterial proteins were identified as calmodulin-binding proteins: SecA, GlpD, and GlpC. We suggest that also these native bacterial proteins might be isolated by the unusual purification procedure including affinity chromatography on calmodulin Sepharose. Whether the identified proteins bind to, and are regulated by, putative bacterial calmodulin-like proteins in Escherichia coli remains to be established. PMID- 26892538 TI - The psychological cycle behind dental appointment attendance: a cross-sectional study of experiences, anticipations, and behavioral intentions. AB - OBJECTIVES: This study explored a promising theoretical model to explain dental patients' experiences and planning behavior for future appointments. The model predicts that patients pass through a 'psychological cycle' when undergoing a course of dental care: past appointment experiences influence their anticipations for future dental visits, which in turn affect behavioral intentions to attend appointments. METHODS: Variables representing the hypothesized model stages and other potentially relevant context variables (dental anxiety, subjective oral health ratings, general anxiety, stress) were assessed by means of a cross sectional online survey (n = 311). Multiple regression analyses were calculated to estimate the model's fit while controlling for potentially confounding factors. RESULTS: Consistent with the hypothesized cycle, recollections of past appointment experiences influenced behavioral intentions to attend future appointments. This association was mediated by evaluations of prior visits and expectations for future appointments. The variables included within this model explained 42% of the variance in attendance intentions when controlling for the potential moderating effects of context variables. CONCLUSIONS: The findings highlight the contribution of cognitive factors, such as evaluations and expectations, to patients' attendance intentions. This knowledge could help find ways to improve treatment expectations to foster better dental service utilization. PMID- 26892537 TI - Divergence time estimates and the evolution of major lineages in the florideophyte red algae. AB - The Florideophyceae is the most abundant and taxonomically diverse class of red algae (Rhodophyta). However, many aspects of the systematics and divergence times of the group remain unresolved. Using a seven-gene concatenated dataset (nuclear EF2, LSU and SSU rRNAs, mitochondrial cox1, and plastid rbcL, psaA and psbA genes), we generated a robust phylogeny of red algae to provide an evolutionary timeline for florideophyte diversification. Our relaxed molecular clock analysis suggests that the Florideophyceae diverged approximately 943 (817-1,049) million years ago (Ma). The major divergences in this class involved the emergence of Hildenbrandiophycidae [ca. 781 (681-879) Ma], Nemaliophycidae [ca. 661 (597-736) Ma], Corallinophycidae [ca. 579 (543-617) Ma], and the split of Ahnfeltiophycidae and Rhodymeniophycidae [ca. 508 (442-580) Ma]. Within these clades, extant diversity reflects largely Phanerozoic diversification. Divergences within Florideophyceae were accompanied by evolutionary changes in the carposporophyte stage, leading to a successful strategy for maximizing spore production from each fertilization event. Our research provides robust estimates for the divergence times of major lineages within the Florideophyceae. This timeline was used to interpret the emergence of key morphological innovations that characterize these multicellular red algae. PMID- 26892539 TI - Development and validation of a UHPLC-UV method for the determination of a prostate secretory protein 94-derived synthetic peptide (PCK3145) in human plasma and assessment of its stability in human plasma. AB - PCK3145 is a synthetic peptide, derived from the Prostate Secreted Protein 94 (PSP94), with promising in vitro and animal in vivo results in prostate cancer. The aim of the present study was to develop and validate a fast and robust ultra high-performance liquid chromatography with ultraviolet detection for the determination of PCK3145 in human plasma which would be suitable for the assessment of PCK3145 stability to proteolytic degradation. Following protein precipitation, chromatographic separation was carried out on an Aeris Peptide C18 column with mobile phase consisting of acetonitrile-water at a flow-rate of 0.50 mL/min. The calibration curve was linear over the range 0.50-20.00 MUg/mL. Intra- and inter-day percentage relative standard deviation and relative error were <=10%. The limit of detection and the lower limit of quantification were 0.15 and 0.50 MUg/mL, respectively. Recovery of PCK3145 from human plasma was >=96%. The peptide presented high stability in whole blood and in human plasma (>98% intact peptide after 24 h incubation at 37 degrees C in human plasma), which represents a distinctive advantage in the therapeutic use of the compound. This is the first validated UHPLC method for the determination of PCK3145 reported, and it was successfully applied in the study of the proteolytic stability of PCK3145 in human plasma ex vivo. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892540 TI - Insights into the distinct roles of MMP-11 in tumor biology and future therapeutics (Review). AB - The biological processes of cancer cells such as tumorigenesis, proliferation, angiogenesis, apoptosis and invasion are greatly influenced by the surrounding microenvironment. The ability of solid malignant tumors to alter the microenvironment represents an important characteristic through which tumor cells are able to acquire specific functions necessary for their malignant biological behaviors. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases with the capacity of remodeling extracellular matrix (ECM) by degrading almost all ECM proteins, which plays essential roles during the invasion and metastasis process of solid malignant tumors, including allowing tumor cells to modify the ECM components and release cytokines, ultimately facilitating protease-dependent tumor progression. MMP-11, also named stromelysin 3, is a member of the stromelysin subgroup belonging to MMPs superfamily, which has been detected in cancer cells, stromal cells and adjacent microenvironment. Differently, MMP-11 exerts a dual effect on tumors. On the one hand MMP-11 promotes cancer development by inhibiting apoptosis as well as enhancing migration and invasion of cancer cells, on the other hand MMP-11 plays a negative role against cancer development via suppressing metastasis in animal models. Overexpression of MMP-11 was discovered in sera of cancer patients compared with normal control group as well as in multiple tumor tissue specimens, such as gastric cancer, breast cancer, and pancreatic cancer. At present, some evidence supports that MMP-11 may work as a significant tumor biomarker for early detection of cancer, tumor staging, prognostic analysis, monitoring recurrence during follow-up and also a potential target for immunotherapy against cancer. In view of the importance of MMP-11 in modifying tumor microenvironment and potent antitumoral effects on solid tumors, there is an urgent need for a deeper understanding of how MMP-11 modulates tumor progression, and exploring its potential clinical application. PMID- 26892541 TI - Methodology of health-related quality of life analysis in phase III advanced non small-cell lung cancer clinical trials: a critical review. AB - BACKGROUND: Health-related quality of life (HRQoL) is recognized as a component endpoint for cancer therapy approvals. The aim of this review was to evaluate the methodology of HRQoL analysis and reporting in phase III clinical trials of first line chemotherapy in advanced non-small cell lung cancers (NSCLC). METHODS: A search in MEDLINE databases identified phase III clinical trials in first-line chemotherapy for advanced NSCLC, published between January 2008 to December 2014. Two authors independently extracted information using predefined data abstraction forms. RESULTS: A total of 55 phase III advanced NSCLC trials were identified. HRQoL was declared as an endpoint in 27 studies (49%). Among these 27 studies, The EORTC questionnaire Quality of Life Questionnaire C30 was used in 13 (48%) of the studies and The Functional Assessment of Cancer Therapy-General was used in 12 (44%) trials. The targeted dimensions of HRQoL, the minimal clinically important difference and the statistical approaches for dealing with missing data were clearly specified in 13 (48.1%), 9 (33.3%) and 5 (18.5%) studies, respectively. The most frequent statistical methods for HRQoL analysis were: the mean change from baseline (33.3%), the linear mixed model for repeated measures (22.2%) and time to HRQoL score deterioration (18.5%). For each targeted dimension, the results for each group, the estimated effect size and its precision were clearly reported in 4 studies (14.8%), not clearly reported in 11 studies (40.7%) and not reported at all in 12 studies (44.4%). CONCLUSIONS: This review demonstrated the weakness and the heterogeneity of the measurement, analysis, and reporting of HRQoL in phase III advanced NSCLC trials. Precise and uniform recommendations are needed to compare HRQoL results across publications and to provide understandable messages for patients and clinicians. PMID- 26892543 TI - From PERV to CRISPR. PMID- 26892542 TI - YY1 inhibits differentiation and function of regulatory T cells by blocking Foxp3 expression and activity. AB - Regulatory T (T(reg)) cells are essential for maintenance of immune homeostasis. Foxp3 is the key transcription factor for T(reg)-cell differentiation and function; however, molecular mechanisms for its negative regulation are poorly understood. Here we show that YY1 expression is lower in T(reg) cells than T(conv) cells, and its overexpression causes a marked reduction of Foxp3 expression and abrogation of suppressive function of Treg cells. YY1 is increased in T(reg) cells under inflammatory conditions with concomitant decrease of suppressor activity in dextran sulfate-induced colitis model. YY1 inhibits Smad3/4 binding to and chromatin remodelling of the Foxp3 locus. In addition, YY1 interrupts Foxp3-dependent target gene expression by physically interacting with Foxp3 and by directly binding to the Foxp3 target genes. Thus, YY1 inhibits differentiation and function of T(reg) cells by blocking Foxp3. PMID- 26892545 TI - Wrong but seminal. PMID- 26892546 TI - Antibacterials: A sweet vaccine. PMID- 26892547 TI - Biomimetic catalysis: Taking on the turnover challenge. PMID- 26892548 TI - Energy storage: Redox flow batteries go organic. PMID- 26892549 TI - Infrared spectroscopy: The acid test for water structure. PMID- 26892544 TI - Isolation and partial characterization of a highly divergent lineage of hantavirus from the European mole (Talpa europaea). AB - Genetically distinct hantaviruses have been identified in five species of fossorial moles (order Eulipotyphla, family Talpidae) from Eurasia and North America. Here, we report the isolation and partial characterization of a highly divergent hantavirus, named Nova virus (NVAV), from lung tissue of a European mole (Talpa europaea), captured in central Poland in August 2013. Typical hantavirus-like particles, measuring 80-120 nm in diameter, were found in NVAV infected Vero E6 cells by transmission electron microscopy. Whole-genome sequences of the isolate, designated NVAV strain Te34, were identical to that amplified from the original lung tissue, and phylogenetic analysis of the full length L, M and S segments, using maximum-likelihood and Bayesian methods, showed that NVAV was most closely related to hantaviruses harbored by insectivorous bats, consistent with an ancient evolutionary origin. Infant Swiss Webster mice, inoculated with NVAV by the intraperitoneal route, developed weight loss and hyperactivity, beginning at 16 days, followed by hind-limb paralysis and death. High NVAV RNA copies were detected in lung, liver, kidney, spleen and brain by quantitative real-time RT-PCR. Neuropathological examination showed astrocytic and microglial activation and neuronal loss. The first mole-borne hantavirus isolate will facilitate long-overdue studies on its infectivity and pathogenic potential in humans. PMID- 26892550 TI - Correction. PMID- 26892551 TI - Remote functionalization through alkene isomerization. AB - Exploiting the reactivity of one functional group within a molecule to generate a reaction at a different position is an ongoing challenge in organic synthesis. Effective remote functionalization protocols have the potential to provide access to almost any derivatives but are difficult to achieve. The difficulty is more pronounced for acyclic systems where flexible alkyl chains are present between the initiating functional group and the desired reactive centres. In this Review, we discuss the concept of remote functionalization of alkenes using metal complexes, leading to a selective reaction at a position distal to the initial double bond. We aim to show the vast opportunity provided by this growing field through selected and representative examples. Our aim is to demonstrate that using a double bond as a chemical handle, metal-assisted long-distance activation could be used as a powerful synthetic strategy. PMID- 26892553 TI - Self-assembled nanospheres with multiple endohedral binding sites pre-organize catalysts and substrates for highly efficient reactions. AB - Tuning reagent and catalyst concentrations is crucial in the development of efficient catalytic transformations. In enzyme-catalysed reactions the substrate is bound-often by multiple non-covalent interactions-in a well-defined pocket close to the active site of the enzyme; this pre-organization facilitates highly efficient transformations. Here we report an artificial system that co encapsulates multiple catalysts and substrates within the confined space defined by an M12L24 nanosphere that contains 24 endohedral guanidinium-binding sites. Cooperative binding means that sulfonate guests are bound much more strongly than carboxylates. This difference has been used to fix gold-based catalysts firmly, with the remaining binding sites left to pre-organize substrates. This strategy was applied to a Au(I)-catalysed cyclization of acetylenic acid to enol lactone in which the pre-organization resulted in much higher reaction rates. We also found that the encapsulated sulfonate-containing Au(I) catalysts did not convert neutral (acid) substrates, and so could have potential in the development of substrate-selective catalysis and base-triggered on/off switching of catalysis. PMID- 26892554 TI - Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage. AB - The hollow cavities of coordination cages can provide an environment for enzyme like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of kcat/kuncat is 2 * 10(5), due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments. PMID- 26892552 TI - Reversible Bergman cyclization by atomic manipulation. AB - The Bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Here we demonstrate a reversible Bergman cyclization for the first time. We induced the on-surface transformation of an individual aromatic diradical into a highly strained ten-membered diyne using atomic manipulation and verified the products by non-contact atomic force microscopy with atomic resolution. The diyne and diradical were stabilized by using an ultrathin NaCl film as the substrate, and the diyne could be transformed back into the diradical. Importantly, the diradical and the diyne exhibit different reactivity, electronic, magnetic and optical properties associated with the changes in the bond topology, and spin multiplicity. With this reversible, triggered Bergman cyclization we demonstrated switching on demand between the two reactive intermediates by means of selective C-C bond formation or cleavage, which opens up the field of radical chemistry for on-surface reactions by atomic manipulation. PMID- 26892555 TI - The role of metal ions in X-ray-induced photochemistry. AB - Metal centres in biomolecules are recognized as being particularly sensitive to radiation damage by X-ray photons. This results in such molecules being both susceptible to an effective X-ray-induced loss of function and problematic to study using X-ray diffraction methods, with reliable structures of the metal centres difficult to obtain. Despite the abundance of experimental evidence, the mechanistic details of radiation damage at metal centres are unclear. Here, using ab initio calculations, we show that the absorption of X-rays by microsolvated Mg(2+) results in a complicated chain of ultrafast electronic relaxation steps that comprise both intra- and intermolecular processes and last for a few hundred femtoseconds. At the end of this cascade the metal reverts to its original charge state, the immediate environment becomes multiply ionized and large concentrations of radicals and slow electrons build up in the metal's vicinity. We conclude that such cascades involving metal ions are essential to our understanding of radiation chemistry and radiation damage in biological environments. PMID- 26892556 TI - An antibacterial vaccination strategy based on a glycoconjugate containing the core lipopolysaccharide tetrasaccharide Hep2Kdo2. AB - Certain non-mammalian cell wall sugars are conserved across a variety of pathogenic bacteria. This conservation of structure, combined with their structural differences when compared with mammalian sugars, make them potentially powerful epitopes for immunization. Here, we report the synthesis of a glycoconjugate that displays the so-called 'inner core' sugars of Gram-negative bacterial cell walls. We also describe an antibacterial vaccination strategy based on immunization with the glycoconjugate and the subsequent administration of an inhibitor that uncovers the corresponding epitope in pathogenic bacteria. The core tetrasaccharide, Hep2Kdo2, a common motif in bacterial lipopolysaccharides, was synthesized and attached via a chain linker to a diphtheria toxin mutant carrier protein. This glycoconjugate generated titres of antibodies towards the inner core tetrasaccharide of the lipopolysaccharide, which were capable of binding the cell-surface sugars of bacterial pathogenic strains including Neisseria meningitidis, Pseudomonas aeruginosa and Escherichia coli. Exposure of bacterial lipopolysaccharide in in vitro experiments, using an inhibitor of capsular polysaccharide transport, enabled potent bacterial killing with antiserum. PMID- 26892558 TI - Dissociative electron attachment to CO2 produces molecular oxygen. AB - Until recently, it was widely regarded that only one reaction pathway led to the production of molecular oxygen in Earth's prebiotic primitive atmosphere: a three body recombination reaction of two oxygen atoms and a third body that removes excess energy. However, an additional pathway has recently been observed that involves the photodissociation of CO2 on exposure to ultraviolet light. Here we demonstrate a further pathway to O2 production, again from CO2, but via dissociative electron attachment (DEA). Using anion-velocity image mapping, we provide experimental evidence for a channel of DEA to CO2 that produces O2(X(3)Sigma(-)g) + C(-). This observed channel coexists in the same energy range as the competitive three-body dissociation of CO2 to give O + O + C(-). The abundance of low-energy electrons in interstellar space and the upper atmosphere of Earth suggests that the contributions of these pathways are significant and should be incorporated into atmospheric chemistry models. PMID- 26892559 TI - Diversification of self-replicating molecules. AB - How new species emerge in nature is still incompletely understood and difficult to study directly. Self-replicating molecules provide a simple model that allows us to capture the fundamental processes that occur in species formation. We have been able to monitor in real time and at a molecular level the diversification of self-replicating molecules into two distinct sets that compete for two different building blocks ('food') and so capture an important aspect of the process by which species may arise. The results show that the second replicator set is a descendant of the first and that both sets are kinetic products that oppose the thermodynamic preference of the system. The sets occupy related but complementary food niches. As diversification into sets takes place on the timescale of weeks and can be investigated at the molecular level, this work opens up new opportunities for experimentally investigating the process through which species arise both in real time and with enhanced detail. PMID- 26892557 TI - Controlled partial interpenetration in metal-organic frameworks. AB - Interpenetration, the entwining of multiple lattices, is a common phenomenon in metal-organic frameworks (MOFs). Typically, in interpenetrated MOFs the sub lattices are fully occupied. Here we report a family of MOFs in which one sub lattice is fully occupied and the occupancy level of the other can be controlled during synthesis to produce frameworks with variable levels of partial interpenetration. We also report an 'autocatenation' process, a transformation of non-interpenetrated lattices into doubly interpenetrated frameworks via progressively higher degrees of interpenetration that involves no external reagents. Autocatenation maintains crystallinity and can be triggered either thermally or by shear forces. The ligand used to construct these MOFs is chiral, and both racemic and enantiopure partially interpenetrated frameworks can be accessed. X-ray diffraction, nonlinear optical microscopy and theoretical calculations offer insights into the structures and dynamic behaviour of these materials and the growth mechanisms of interpenetrated MOFs. PMID- 26892560 TI - Extreme compressibility in LnFe(CN)6 coordination framework materials via molecular gears and torsion springs. AB - The mechanical flexibility of coordination frameworks can lead to a range of highly anomalous structural behaviours. Here, we demonstrate the extreme compressibility of the LnFe(CN)6 frameworks (Ln = Ho, Lu or Y), which reversibly compress by 20% in volume under the relatively low pressure of 1 GPa, one of the largest known pressure responses for any crystalline material. We delineate in detail the mechanism for this high compressibility, where the LnN6 units act like torsion springs synchronized by rigid Fe(CN)6 units performing the role of gears. The materials also show significant negative linear compressibility via a cam like effect. The torsional mechanism is fundamentally distinct from the deformation mechanisms prevalent in other flexible solids and relies on competition between locally unstable metal coordination geometries and the constraints of the framework connectivity, a discovery that has implications for the strategic design of new materials with exceptional mechanical properties. PMID- 26892562 TI - Corrigendum: Recent advances in the construction of antibody-drug conjugates. PMID- 26892561 TI - Enantioselective aldol reactions with masked fluoroacetates. AB - Despite the growing importance of organofluorines as pharmaceuticals and agrochemicals, the stereoselective introduction of fluorine into many prominent classes of natural products and chemotherapeutic agents is difficult. One long standing unsolved challenge is the enantioselective aldol reaction of fluoroacetate to enable access to fluorinated analogues of medicinally relevant acetate-derived compounds, such as polyketides and statins. Herein we present fluoromalonic acid halfthioesters as biomimetic surrogates of fluoroacetate and demonstrate their use in highly stereoselective aldol reactions that proceed under mild organocatalytic conditions. We also show that the methodology can be extended to formal aldol reactions with fluoroacetaldehyde and consecutive aldol reactions. The synthetic utility of the fluorinated aldol products is illustrated by the synthesis of a fluorinated derivative of the top-selling drug atorvastatin. The results show the prospects of the method for the enantioselective introduction of fluoroacetate to access a wide variety of highly functionalized fluorinated compounds. PMID- 26892563 TI - Corrigendum: Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization. PMID- 26892565 TI - Lawrencium's place at the table. PMID- 26892564 TI - Corrigendum: Sustained gastrointestinal activity of dendronized polymer-enzyme conjugates. PMID- 26892566 TI - Oesophageal dilatation with the aid of a flexible bronchoscope. PMID- 26892567 TI - Intolerance for approach of ambiguity in social anxiety disorder. AB - Previous research has utilised the approach-avoidance task (AAT) to measure approach and avoidance action tendencies in socially anxious individuals. "Neutral" social stimuli may be perceived as ambiguous and hence threatening to socially anxious individuals, however it is unclear whether this results in difficulty approaching ambiguous ("neutral") versus unambiguous threat (e.g. disgust) faces (i.e. intolerance of ambiguity). Thirty participants with social anxiety disorder (SADs) and 29 non-anxious controls completed an implicit AAT in which they were instructed to approach or avoid neutral and disgust faces (i.e. pull or push a joystick) based on colour of the picture border. Results indicated that SADs demonstrated greater difficulty approaching neutral relative to disgust faces. Moreover, intolerance for approach of ambiguity predicted social anxiety severity while controlling for the effects of trait anxiety and depression. Our results provide further support for the role of intolerance of ambiguity in SAD. PMID- 26892568 TI - Survival of the Fittest Nanojar: Stepwise Breakdown of Polydisperse Cu27-Cu31 Nanojar Mixtures into Monodisperse Cu27(CO3) and Cu31(SO4) Nanojars. AB - Nanojars are emerging as a class of anion sequestration agents of unparalleled efficiency. Dinegative oxoanions (e.g., carbonate, sulfate) template the formation of a series of homologous nanojars [Cu(OH)(pyrazolato)]n (n=27-31). Pyridine selectively transforms less stable, larger CO3(2-) nanojars (n=30, 31) into more stable, smaller ones (n=27, 29), but leaves all SO4(2-) nanojars (n=27 29, 31) intact. Ammonia, in turn, transforms all less stable nanojars into the most stable one and allows the isolation of pure [CO3(2-)?{Cu(OH)(pz)}27] and [SO4(2-)?{Cu(OH)(pz)}31]. A comprehensive picture of the solution and solid-state intricacies of nanojars was revealed by a combination of variable temperature NMR spectroscopy, tandem mass spectrometry, and X-ray crystallography. PMID- 26892570 TI - Gene expression profile changes induced by acute toxicity of [C16 mim]Cl in loach (Paramisgurnus dabryanus). AB - Ionic liquids (ILs) are widely used as reaction media in various commercial applications. Many reports have indicated that most ILs are poorly decomposed by microorganisms and are toxic to aquatic organisms. In this study, differential gene expression profiling was conducted using a suppression subtraction hybridization cDNA library from hepatic tissue of the loach (Paramisgurnus dabryanus) after exposure to 1-hexadecyl-3-methylimidazolium chloride ([C16 mim]Cl), a representative IL. Two hundred and fifty-nine differentially expressed candidate genes, whose expression was altered by >2.0-fold by the [C16 mim]Cl treatment, were identified, including 127 upregulated genes and 132 downregulated genes. A gene ontology analysis of the known genes isolated in this study showed that [C16 mim]Cl-responsive genes were involved in cell cycle, stimulus response, defense response, DNA damage response, oxidative stress responses, and other biological responses. To identify candidate genes that may be involved in [C16 mim]Cl-induced toxicity, 259 clones were examined by Southern blot macroarray hybridization, and 20 genes were further characterized using quantitative real time polymerase chain reaction. Finally, six candidate genes were selected, including three DNA damage response genes, two toxic substance metabolic genes, and one stress protein gene. Our results indicate that these changes in gene expression are associated with [C16 mim]Cl-induced toxicity, and that these six candidate genes can be promising biomarkers for detecting [C16 mim]Cl-induced toxicity. Therefore, this study demonstrates the use of a powerful assay to identify genes potentially involved in [C16 mim]Cl toxicity, and it provides a foundation for the further study of related genes and the molecular mechanism of [C16 mim]Cl toxicity. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 404 416, 2017. PMID- 26892571 TI - Primary Sarcopenia in Older People with Normal Nutrition. AB - OBJECTIVE: The aim of this study was to investigate the presence of primary sarcopenia in older patients with normal nutrition and to assess the relationships between the primary sarcopenia with anthropometric measurements. DESIGN AND METHODS: In this prospective clinical cross-sectional study, six hundred patients who applied to Polyclinic of Geriatrics between dates 2010 and 2011 have been evaluated. The 386 patients who were supposed to have potential secondary sarcopenia were excluded from the study. Age, gender, weight, height, BMI, calf and waist circumference, ongoing medications, additional diseases of the 214 patients included in the study have been surveyed. The sarcopenia criteria of EWSGOP have been applied. RESULTS: Two hundred fourteen cases included in the study were composed of 148 female and 66 male subjects. Mean age was 71.8 +/- 2.1 years. Sarcopenia was detected in 105 (49%) subjects while 109 (51%) were normal. Sixty-four female (61%) and 41 (39%) male subjects were sarcopenic. Normal group included 84 female (77%) and 25 male (23%) subjects. Incidence of sarcopenia was found higher in the female patients (p<0.001). No statistically significant difference was detected between sarcopenic and normal groups with respect to age, height, weight, calf circumference and evaluation tests. Waist circumference was higher in the sarcopenic group than the normal group (p=0.02). When both groups were analyzed for BMI; 53 (51%) of the 105 sarcopenic patients had BMI over 30 kg/m2 while 29 (27%) and 23 (22%) patients had BMI of 25-30 kg/m2 and below 25 kg/m2, respectively. Incidence of sarcopenia was significantly higher in the group with BMI over 30 kg/m2 when compared with the groups with BMI of 25-30 kg/m2 and below 25 kg/m2 (p=0.01). CONCLUSION: Sarcopenia that makes older people physically dependent and decreases their quality of life that receive sufficient nutritional support and are also obese should be comprehensively investigated with respect to presence of sarcopenia. PMID- 26892569 TI - A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder. AB - Gamma-amino butyric acid (GABA) and glutamate are the major inhibitory and excitatory neurotransmitters in the mammalian central nervous system, respectively, and have been associated with suicidal behavior and major depressive disorder (MDD). We examined the relationship between genotype, brain transcriptome, and MDD/suicide for 24 genes involved in GABAergic and glutamatergic signaling. In part 1 of the study, 119 candidate SNPs in 24 genes (4 transporters, 4 enzymes, and 16 receptors) were tested for associations with MDD and suicidal behavior in 276 live participants (86 nonfatal suicide attempters with MDD and 190 non-attempters of whom 70% had MDD) and 209 postmortem cases (121 suicide deaths of whom 62% had MDD and 88 sudden death from other causes of whom 11% had MDD) using logistic regression adjusting for sex and age. In part 2, RNA-seq was used to assay isoform-level expression in dorsolateral prefrontal cortex of 59 postmortem samples (21 with MDD and suicide, 9 MDD without suicide, and 29 sudden death non-suicides and no psychiatric illness) using robust regression adjusting for sex, age, and RIN score. In part 3, SNPs with subthreshold (uncorrected) significance levels below 0.05 for an association with suicidal behavior and/or MDD in part 1 were tested for eQTL effects in prefrontal cortex using the Brain eQTL Almanac (www.braineac.org). No SNPs or transcripts were significant after adjustment for multiple comparisons. However, a protein coding transcript (ENST00000414552) of the GABA A receptor, gamma 2 (GABRG2) had lower brain expression postmortem in suicide (P = 0.01) and evidence for association with suicide death (P = 0.03) in a SNP that may be an eQTL in prefrontal cortex (rs424740, P = 0.02). These preliminary results implicate GABRG2 in suicide and warrant further investigation and replication in larger samples. PMID- 26892572 TI - The Healthy Core Metabolism: A New Paradigm for Primary Preventive Nutrition. AB - Research in preventive nutrition aims at elucidating mechanism by which our diet helps us to remain in good health through optimal physiological functions. However, despite decades of accumulated data in human nutrition and regular subsequent nutritional recommendations, obesity and type 2 diabetes epidemics continue to progress worldwide each year leading to a regular decrease of the Healthy Life Years, notably in Western countries. Such a paradox may be explained by the Nutrition Transition, the extreme application of the reductionist paradigm in nutrition research, the lack of nutritional education and a too strong focus on curative nutrition in at risk/ill subjects. In this position paper, we hypothesized that researchers should focus more on healthy subjects, from birth until maturity. Rather than exploring what differentiates healthy and at risk/ill subjects, we propose to thoroughly study what characterizes a healthy state and its underlying metabolism. We define it as the Healthy Core Metabolism which remains stable whatever energy inputs (diets) and outputs (exercise), genetic background and external/internal stress, e.g., temporary illnesses. As a basis for Healthy Core Metabolism investigation, we observed that main physiological and ubiquitous functions of human organism, i.e., the neuro-vasculo-sarco osteoporotic system, tend to follow a concave curve with common phases of growth, optimum, and decline. Finally, we hypothesized that true primary preventive nutrition should focus on the growth phase to reach the maximum capital of a given physiological function so that - whatever the further decline -, Healthy Life Years may approach or coincide with theoretical Life Expectancy. PMID- 26892573 TI - Associations of Low Muscle Mass and the Metabolic Syndrome in Caucasian and Asian Middle-aged and Older Adults. AB - OBJECTIVE: Age-related declines in skeletal muscle mass may confer significant metabolic consequences for older adults. Associations of low muscle mass and metabolic syndrome (MetS) in Caucasians, and comparisons with associations observed in Asian populations, have not been reported. We examined associations of low muscle mass and metabolic syndrome (MetS) in Asian and Caucasian middle aged and older men and women using criteria for low muscle mass. DESIGN, SETTING AND PARTICIPANTS: Two population-based studies of Australian (Tasmanian Older Adult Cohort Study; TASOAC; N=1005) and Korean (Korean Sarcopenic Obesity Study; KSOS; N=376) community-dwelling adults, mean age 62 and 58 years, respectively. MEASUREMENTS: Appendicular lean mass (aLM) determined by dual-energy X-ray absorptiometry and normalised to height squared (aLM/Ht2), weight (aLM/Wt) or body mass index (aLM/BMI). Participants in the lowest sex-specific 20% for aLM measures were defined as having low muscle mass. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Although Australians demonstrated generally unfavourable anthropometric and metabolic characteristics compared to Koreans, prevalence of MetS was similar (29.5% in Australians and 31.4% in Koreans, respectively). Low aLM/Ht2 was associated with significantly reduced likelihood of MetS in both Australians (OR: 0.30, 95% CI 0.19 - 0.46) and Koreans (OR: 0.31, 95% CI 0.16 - 0.62). Conversely, low aLM/BMI was associated with increased odds for MetS in Australians (OR: 1.78, 95% CI 1.12 - 2.84), but not Koreans (OR: 1.33, 95% CI = 0.67 - 2.64). CONCLUSION: Low aLM/BMI is associated with significantly increased likelihood of MetS in Australian adults, but not Koreans, suggesting potential differences in effects of low muscle mass relative to body mass on cardiometabolic health in Caucasian and Asian middle-aged and older adults. Low muscle mass relative to height is associated with reduced likelihood of MetS in both populations. PMID- 26892574 TI - Body Composition Assessment and Nutritional Status Evaluation in Men and Women Portuguese Centenarians. AB - OBJECTIVES: To assess body composition, nutritional status and its differences between genders in a sample of Portuguese centenarians. DESIGN: Observational cross-sectional study. SETTING: Centenarians recruited in Portugal, able to give informed consent. PARTICIPANTS: A total of 252 subjects, with a median age of 100 years, mostly women (77.8%) who accepted to participate in the study, during the period of 2012 to 2014. MEASUREMENTS: Anthropometric data collected (weight, height, BMI, waist circumference, hip and waist/hip ratio) were evaluated according to WHO criteria. A portable tetrapolar bioimpedance analyzer was used to calculate body composition and to assess resting metabolism. Nutritional status was evaluated according to three different criteria: BMI, waist circumference and body fat percentage using anthropometric equations and bioimpedance. RESULTS: We observed an overall mean weight of 51.02+/-11.03Kg, height of 1.55+/-0.07m and a BMI of 21.07+/-3.69Kg/m2. For most of the evaluated parameters, we found substantial differences between genders. The prevalence of underweight and overweight were 25.3% and 13.3%, respectively. Only 5 subjects were obese. Overweight subjects were mostly men (W=10.6% vs. M=22.6%), whereas women were more underweight (W=28.7% vs. M=13.2%). When considering the waist circumference, 26.5% were above the cut-off value. Most of centenarians (72.9%) had a healthy level of visceral fat. This measurement was highly correlated with waist circumference (r= 0.687, p<0.001). The mean of body fat mass was 10.69+/ 6.50Kg, fat-free mass 40.87+/-7.60Kg and total body water 27.54+/-6.25Kg. According to body fat mass criteria assessed by bioimpedance, the prevalence of obesity in study population was 6.0% with no gender differences (p = 0.225). Obesity prevalence using anthropometric equations was higher (Deurenberg: 77.7% and Gallagher: 42.8%) than the obtained value by bioimpedance analysis, although according to Bland-Altman analysis both equations showed a good agreement (Deurenberg: 95.8% and Gallagher: 97%) with bioimpedance method. The prevalence of hypohydration (12.9%) was tendentiously higher in women compared to men (W= 15.4% vs. M= 5.0%, p=0.087). Despite the frequency of osteoporosis was higher in women (W = 71.85% vs. M = 28.15%), 95% of men revealed criteria for osteoporosis. Resting metabolic rate (RMR) was significantly different between genders using bioimpedance analysis (W= 1123.33+/- 173.91; M= 1350.10+/- 188.88; p<0.001) or Harris Benedict equation (W= 934.92+/- 102.60; M= 1018.85+/- 171.68; p=0.001). Bland- Altman analysis between methods indicate that there was an agreement of 97.6%. The overall mean metabolic age obtained was 83.52+/-1.11 years, well below the chronologic age (p<0.001). CONCLUSION: In Portuguese centenarians, clinical and nutritional approach should be improved on the gender basis. In relation to nutritional status, centenarians were more frequently underweight than overweight. The thinness could be a natural process, contributing for the longevity being rather overweight a reducing factor in life expectancy. BMI and waist circumference showed a good correlation with body fat percentage. Despite the results of Bland- Altman analysis, Deurenberg and Gallagher equations are not suitable to evaluate obesity prevalence in centenarians. Harris Benedict equation seems to be a good option to measure RMR in centenaries, when BIA is not available. Body composition and nutritional characterization of Portuguese centenarians are relevant contribution in scientific evidence production for the action plan of healthy ageing in Europe (2012-2020) and also for clinical practice. PMID- 26892575 TI - Associations of Buccal Cell Telomere Length with Daily Intake of beta-Carotene or alpha-Tocopherol Are Dependent on Carotenoid Metabolism-related Gene Polymorphisms in Healthy Japanese Adults. AB - OBJECTIVE: Telomere length shortening is modulated not only by aging, but also by both genetic and environmental factors. The aim of this study was to investigate the interactions between antioxidant nutrient metabolism-related gene single nucleotide polymorphisms (the genetic factors) and nutrient intake (the environmental factors) in their effects on telomere length shortening. SETTING AND PARTICIPANTS: Data were collected on the relative telomere lengths (RTLs) of buccal cells and the habitual food intake of 70 healthy Japanese adults. MEASUREMENTS: All subjects were genotyped for two common single nucleotide polymorphisms: rs6564851 in the beta-carotene-15,15'-mono-oxygenase 1 (BCMO1) gene and rs362090 in the intestine-specific homeobox (ISX) gene. RESULTS: Univariate analysis revealed that buccal RTL was not significantly modulated by either age or gender. Then, we subdivided the study population into four groups based on combinations of the rs6564851 and rs362090 genotypes. After this subdivision, we showed a positive effect of daily alpha- or beta-carotene intake on buccal RTL in the ISX rs362090 G-allele carrier + BCMO1 rs6564851 GG-genotype group (p = 0.026). Additionally, daily intake of another antioxidative fat soluble vitamin, alpha-tocopherol, was positively associated with buccal RTL in the ISX rs362090 AA-homozygote + BCMO1 rs6564851 T-allele carrier group (p = 0.037). CONCLUSION: Our study clearly indicates that high dietary intake of the antioxidants alpha, beta-carotene and alpha-tocopherol protects buccal cells from RTL shortening, depending on the genetic background of antioxidant vitamin related genes. PMID- 26892576 TI - Living Unnoticed: Cognitive Impairment in Older People with Multimorbidity. AB - OBJECTIVES: To investigate the correlation between MMSE <= 23 and the presence of a diagnosis of dementia in the medical record in a population with multimorbidity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was part of the Ambulatory Geriatric Assessment - a Frailty Intervention Trial (AGe FIT; N = 382). Participants were community dwelling, aged >= 75 years, had received inpatient hospital care at least three times during the past 12 months, and had three or more concomitant diagnoses according to the International Classification of Diseases, 10th revision. MEASUREMENTS: The Mini Mental State Examination (MMSE) was administered at baseline. Medical records of participants with MMSE scores < 24 were examined for the presence of dementia diagnoses and two years ahead. RESULTS: Fifty-three (16%) of 337 participants with a measure of MMSE had a MMSE scores < 24. Six of these 53 (11%) participants had diagnoses of dementia (vascular dementia, n = 4; unspecified dementia, n = 1; Alzheimers disease, n = 1) according to medical records; 89% did not. CONCLUSIONS: A MMSE score < 24 is not well correlated to a diagnosis of dementia in the medical record in a population of elderly with multimorbidity. This could imply that cognitive decline and the diagnosis of dementia remain undetected in older people with multimorbidity. Proactive care of older people with multimorbidity should focus on cognitive decline to detect cognitive impairment and to provide necessary help and support to this very vulnerable group. PMID- 26892577 TI - Serum Cholesterol Levels within the High Normal Range Are Associated with Better Cognitive Performance among Chinese Elderly. AB - OBJECTIVES: The association between cognitive function and cholesterol levels is poorly understood and inconsistent results exist among the elderly. The purpose of this study is to investigate the association of cholesterol level with cognitive performance among Chinese elderly. DESIGN: A cross-sectional study was implemented in 2012 and data were analyzed using generalized additive models, linear regression models and logistic regression models. SETTING: Community-based setting in eight longevity areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 85.8+/-12.0 years) participated in this study. MEASUREMENTS: Total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) concentration were determined and cognitive impairment was defined as Mini-Mental State Examination (MMSE) score <=23. RESULTS: There was a significant positive linear association between TC, TG, LDL-C, HDL-C and MMSE score in linear regression models. Each 1 mmol/L increase in TC, TG, LDL-C and HDL-C corresponded to a decreased risk of cognitive impairment in logistic regression models. Compared with the lowest tertile, the highest tertile of TC, LDL-C and HDL-C had a lower risk of cognitive impairment. The adjusted odds ratios and 95% CI were 0.73(0.62-0.84) for TC, 0.81(0.70-0.94) for LDL-C and 0.81(0.70-0.94) for HDL-C. There was no gender difference in the protective effects of high TC and LDL-C levels on cognitive impairment. However, for high HDL-C levels the effect was only observed in women. High TC, LDL-C and HDL-C levels were associated with lower risk of cognitive impairment in the oldest old (aged 80 and older), but not in the younger elderly (aged 65 to 79 years). CONCLUSIONS: These findings suggest that cholesterol levels within the high normal range are associated with better cognitive performance in Chinese elderly, specifically in the oldest old. With further validation, low cholesterol may serve a clinical indicator of risk for cognitive impairment in the elderly. PMID- 26892578 TI - The Independent Role of Inflammation in Physical Frailty among Older Adults with Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease. AB - OBJECTIVES: To examine the independent and combined effects of inflammation and endocrine dysregulation on (i) baseline frailty status and (ii) frailty progression at one year, among cognitively impaired community dwelling older adults. DESIGN: Prospective cohort study. SETTING: Tertiary Memory Clinic. METHODS: We recruited patients with mild cognitive impairment and mild-moderate Alzheimer's disease. Physical frailty status was assessed at baseline and 1-year. Blood biomarkers of systemic inflammation [interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha)] and anabolic hormones [insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS)] were measured at baseline and examined in relation to physical frailty status at baseline and progression at 1 year. Each subject was categorized as (i) neither pro-inflammatory nor endocrine deficient, (ii) pro-inflammatory (IL-6 or TNF-alpha, or both, being in highest quartile) but not endocrine deficient, (iii) endocrine deficient (IGF-1 or DHEAS, or both, being in lowest quartile) but not pro-inflammatory and (iv) both pro inflammatory and endocrine deficient. RESULTS: Twenty (20.2%) of 99 subjects were physically frail at baseline. There was no association between severity of cognitive impairment and baseline frailty status, but the frail group had significantly greater hippocampal atrophy (median MTA: 2 (2-3) vs 1 (1-2), p=0.010). TNF-alpha was significantly higher in subjects who were physically frail at baseline (median TNF-alpha: 1.30 (0.60-1.40) vs 0.60 (0.50-1.30) pg/mL, p=0.035). In multiple logistic regression adjusted for age and gender, a pro inflammatory state in the absence of concomitant endocrine deficiency was significantly associated with physical frailty at baseline (OR=4.99, 95% C.I 1.25 19.88, p=0.023); this was no longer significant when MTA score was included in the model. Isolated pro-inflammatory state (without endocrine deficiency) significantly increased the odds of frailty progression (OR=4.06, 95% CI 1.09 15.10, p=0.037) at 1-year. The combination pro-inflammatory and endocrine deficient state was not significantly associated with either baseline or progressive physical frailty. CONCLUSION: A pro-inflammatory state exerts differential effects on physical frailty, contributing to the increased risk of baseline and progressive frailty only in the absence of a concomitant endocrine deficient state, with potential mediation via neurodegeneration. PMID- 26892579 TI - Calcium and Vitamin D Use among Older Adults in U.S.: Results from National Survey. AB - OBJECTIVE: This study was conducted to describe a 10-year trend of the supplement from 2000 to 2009 and to evaluate age, gender and racial disparities using a national level health data. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: Data collected from patient visit records to stand-alone US ambulatory care clinics. Visits made by men and women who were 40 years of age and older were included (n=175,830). MEASUREMENTS: Overall prevalence of recorded calcium and vitamin D use for osteoporosis prevention and treatment, and annual visit rates were estimated by age, gender, race, insurance types, physician specialties, geographical regions, and metropolitan status using chi square test. Multivariate logistic regression was conducted to determine potential predictive factors for calcium and vitamin D supplements. RESULTS: An increase in yearly trend of calcium and vitamin D supplements was observed. The increase was proportional to patients' age (p<0.05) and female gender was a strong predictor of calcium and vitamin D supplement (p<0.0001).Visits made by blacks were significantly less likely to be associated with the supplement (<0.05). Visits associated with self-pay and Medicaid was less likely to be recorded with vitamin D (p<0.05) but not calcium supplements. Osteoporosis diagnosis was an independent predictor of calcium and vitamin D records (p<0.0001). CONCLUSIONS: In spite of the observed increases in the trend of visits associated with calcium and vitamin D supplements, variability in the access to the medications was observed. More focused strategies targeting elderly, men, or black population are needed to maintain and improve adequate calcium and vitamin D supplements. PMID- 26892580 TI - Handgrip Strength Cutoff Points to Identify Mobility Limitation in Community dwelling Older People and Associated Factors. AB - BACKGROUND: Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass and strength. The specific threshold of muscle weakness that leads to mobility limitations has not been identified. OBJECTIVES: To determine the best cutoff point of handgrip strength for identifying mobility limitation and to investigate the factors associated with muscle weakness and mobility limitation in community-dwelling older people. DESIGN: Transversal study. SETTING: Cities of Belo Horizonte, Barueri and Santa Cruz in Brazil. PARTICIPANTS: 1374 community-dwelling older people from the Frailty study in Brazilian older people (FIBRA Study). MEASUREMENTS: Outcomes included muscle weakness determined according to gender-specific handgrip strength cutoff points generated by Receiver Operating Characteristic curves, mobility limitation defined as a gait speed <= 0.8 m/s; and a combination of both muscle weakness and mobility limitation. Associated factors included socio-demographic variables, lifestyle, anthropometrics, health conditions, use of health services and disability. RESULTS: The cutoff points of handgrip strength with the best balancing between sensitivity and specificity for mobility limitation were 25.8 kgf for men (sensitivity 69%, specificity 73%) and 17.4 kgf (sensitivity 60%, specificity 66%) for women. Age and disability in instrumental activities of daily living were associated with all outcomes. Women had greater odds of mobility limitation than men. Physical inactivity, body fat, diabetes, depression, sleeping disturbances, number of medications and occurrence of falls remained as significant associated factors in the final model. CONCLUSIONS: Handgrip strength can be a useful tool to identify mobility limitation in clinical practice. Interventions to prevent or minimize impacts of sarcopenia should stimulate physical activity and improvement of body composition in addition to the management of chronic diseases and disabilities. PMID- 26892581 TI - Healthy Eating Exploratory Program for the Elderly: Low Salt Intake in Congregate Meal Service. AB - OBJECTIVES: This study reported on an exploratory program to help the low income elderly improve healthy eating behavior, specifically by reducing salt intake. DESIGN: We conducted an exploratory program for 4 weeks for this study. The exploratory program involved offering menus with reduced salt and providing education on healthy eating. After the exploratory program, a survey of the elderly and in-depth interviews allowed us to evaluate the program for foodservice providers (dietitian, social workers, and volunteer workers). This study included both foodservice workers and elderly who actually used the foodservice in a congregate meal service system. This is a unique approach. SETTING: A congregate meal service center in Seoul, Korea. PARTICIPANTS: Seventy four elderly in a congregate meal service center. MEASUREMENTS: Demographics were collected, and the healthy eating program and healthy eating education for elderly respondents were evaluated. RESULTS: The elderly showed high satisfaction with the exploratory program for healthy eating. We found no significant differences in satisfaction with the program between the elderly who attended education sessions and those who did not, but more of the elderly from the education sessions showed positive behavioral change intentions. CONCLUSION: The exploratory program influenced to reduce the salt intake of the elderly in congregate meal service. This study suggests cooperation of foodservice providers and the support of administrators is critical to the success of such programs. PMID- 26892582 TI - Effect of Vitamin K on Vascular Health and Physical Function in Older People with Vascular Disease--A Randomised Controlled Trial. AB - BACKGROUND AND AIMS: Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease. METHODS AND RESULTS: A double blind, randomised, placebo-controlled trial. Participants aged <= 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform. RESULTS: 80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs 6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (-130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference -0.3% [95%CI -1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (-0.8m/s [95%CI -1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged. CONCLUSIONS: Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease. PMID- 26892584 TI - Low Hemoglobin A1c Increases the Risk of Disability in Community-dwelling Older Non-diabetics Adults. AB - OBJECTIVE: To describe the health characteristics of individuals with low HbA1c levels and evaluate the association between HbA1c level and disability or all cause mortality in non-diabetic older adults. DESIGN: Prospective observational cohort study. SETTING: Seongnam, Gyeongi Province, Korea. PARTICIPANTS: Among the 1,000 community-dwelling Koreans >= 65 years of age who were followed for 5 years, 760 non-diabetic individuals were analyzed. MEASUREMENTS: Activities of Daily Living (ADL) and Instrumental ADL (IADL) were evaluated and mortality data were obtained from the National Statistics Office of Korea. RESULTS: The mean age was 76.3 (SD 9.0) years, and 319 subjects (42.0%) were male. Lower level of HbA1c was associated with less frequent hypertension and less frequent use of aspirin or statin, and lower values of body mass index, hematocrit, total iron-binding capacity, albumin, and cholesterol level. The participants were categorized into 3 groups according to their HbA1c (group I, < 5.5%; group II, 5.5~5.9%; and group III, 6.0 ~ 6.4%). Although, there was no significant difference in functional status according to baseline HbA1c level, disability was more frequently observed as the HbA1c level decrease (18.3% in group I, 12.5% in group II, and 5.3% in group III, p=0.029) at the 5-year follow-up evaluation. There were 172 deaths (22.6%) during the follow-up period. There was no significant difference in mortality among the groups, however, group I had a 2.071-fold higher risk for the incident disability or mortality over group III after adjusting age, gender, and possible confounder (95% CI: 1.040 ~ 4.124, p=0.038). CONCLUSIONS: Lower level of HbA1c was associated with an increased risk of disability in non-diabetic older adults. PMID- 26892583 TI - Effect of Lifestyle Intervention on the Hormonal Profile of Frail, Obese Older Men. AB - OBJECTIVE: Obesity-associated hypogonadism is hypothesized to be due to the suppressive effect of high estradiol (from an increase in aromatase activity present in the abundant adipose tissue) on the hypothalamic-pituitary-gonadal unit resulting in low testosterone production. Although weight loss has been found to be effective in reducing estradiol and raising testosterone levels in studies of younger men, its effect in frail, obese older men is understudied. Thus, the objective of this study was to determine the effect of lifestyle intervention on hormone levels in frail, obese older men. DESIGN: Randomized controlled trial of lifestyle intervention in frail, obese older men (>=65 yo) for 1 year. SETTING: University hospital. METHODS: Forty frail, obese elderly men were randomized, for a 52-week study, to any of the following treatment groups: (1) control group, (2) diet-induced weight loss group (diet group), (3) exercise training group (exercise group), and (4) diet-induced weight loss and exercise training group (diet-exercise group). The objective was to achieve a ~10 % weight loss at 6 months and maintain this weight for an additional 6 months. Physical function was assessed by the modified physical performance testing (modified PPT). Estradiol was measured by radioimmunoassay, testosterone by automated immunoassay, and sex hormone-binding globulin by enzyme-linked immunoassay. RESULTS: After 12 months of intervention, diet alone resulted in a weight loss of -10.1 +/- 1.9 kg in the diet group and -9.1 +/- 0.9 kg in the diet-exercise group. This resulted in a significant decrease (both p<0.05) in total estradiol compared to baseline among subjects in the diet (-2.5 +/- 1.3 pg/ml) and diet exercise group (-2.2 +/- 4.0 pg/ml). Free estradiol index also significantly decreased (both p <0.05) in both the diet (-0.39 +/- 0.14 pmol/nmol) and diet exercise (-0.52 +/- 0.12 pmol/nmol) group. Total testosterone significantly increased (p<0.05) in response to diet (71.0 +/- 21.0 ng/dl) and diet-exercise (49.9 +/- 15.5 pg/ml) resulting in values of 287.0 +/- 28.1 ng/dl in the diet and 317.6 +/- 33.1 ng/dl in the diet-exercise group. However, because there was a significant increase in sex hormone-binding globulin levels in both the diet and diet-exercise groups, free testosterone index and the changes in free testosterone index were not significant compared to baseline. Regardless of changes in hormonal levels, patients in the diet, exercise, and diet-exercise groups experienced significant improvements in the modified PPT from baseline. CONCLUSION: Weight loss from lifestyle intervention resulted in significant decreases in total and free estradiol levels in frail, obese older men, but this did not result in a clinically important increase in total testosterone nor a significant increase in free testosterone. Thus, alternative forms of treatment in addition to lifestyle intervention may be necessary to improve the hormonal profile among these patients. Nevertheless, whether further improvement in hormonal profile would result in better physical performance than what can be achieved by lifestyle alone in these subjects remains uncertain. PMID- 26892585 TI - Influence of Thoracic Aortic Inflammation and Calcifications on Arterial Stiffness and Cardiac Function in Older Subjects. AB - BACKGROUND: Vascular aging is accompanied by gradual remodeling affecting both arterial and cardiac structure and mechanical properties. Hypertension is suggested to exert pro-inflammatory actions enhancing arterial stiffness. OBJECTIVE: To determine the influence of thoracic aortic inflammation and calcifications on arterial stiffness and cardiac function in hypertensive and normotensive older subjects. DESIGN: A prospective study. SETTING: An acute geriatrics ward of the University Hospital of Nancy in France. SUBJECTS: Thirty individuals >= 65 years were examined, including 15 hypertensive subjects and 15 controls well-matched for age and sex. MEASUREMENTS: Applanation tonometry was used to measure aortic pulse wave velocity (AoPWV) and carotid/brachial pulse pressure amplification (PPA). Left ventricular parameters were measured with magnetic resonance imaging. Local thoracic aortic inflammation and calcification were measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Biomarkers of low-grade inflammation were also quantified. RESULTS: AoPWV was higher in elderly hypertensive subjects comparatively to normotensive controls (15.5+/-5.3 vs. 11.9+/-2.5, p=0.046), and hypertensives had a higher calcification volume. In the overall population, calcifications of the thoracic descending aorta and inflammation of the ascending aorta accounted for respectively 18.1% (p=0.01) and 9.6% (p=0.07) of AoPWV variation. Individuals with high levels of calcifications and/or inflammation had higher AoPWV (p=0.003). Inflammation had a negative effect on PPA explaining 13.8% of its variation (p<0.05). CONCLUSION: This study highlights the importance of local ascending aortic inflammation as a potential major actor in the determination of PPA while calcifications and hypertension are more linked to AoPWV. Assessment of PPA in the very elderly could provide complementary information to improve diagnostic and therapeutic strategies targeting ascending aortic inflammation. PMID- 26892587 TI - Energy and Protein Intake, Anthropometrics, and Disease Burden in Elderly Home care Receivers--A Cross-sectional Study in Germany (ErnSIPP Study). AB - OBJECTIVE: To date, no study has examined the nutritional status and disease burden of elderly home-care receivers living in Germany. Aim of this cross sectional study was, first, to assess disease burden and nutritional status, denoted in anthropometrics, and, second, to investigate associations between anthropometrics and disease burden. DESIGN: Cross-sectional multi-centre study. SETTING: Home-care receivers living in three urban areas of Germany in 2010. PARTICIPANTS: 353 elderly (>64 years) in home care (128 males aged 79.1 +/-7.8 years, 225 females aged 82.0 +/-7.5 years). MEASUREMENTS: Nutritional status was assessed by body mass index (BMI), mid upper arm circumference (MUAC) and calf circumference (CC). Medical conditions were assessed in personal interviews. A 3 day prospective nutrition diary was kept. Metric data are reported as mean+/-SD or median (interquartile range), p<0.05 was considered significant. RESULTS: Most participants were substantially (59%), and 11% severest in need of care. The seniors suffered from 5 (4-7) chronic diseases; dementia, depression, stroke, and respiratory illness were most prevalent (each 20-40%). More than one-third of participants had only moderate or poor appetite, nearly half were unable to eat independently. Chewing problems were reported for 52% of study participants, and more than one quarter of elderly had swallowing problems. Daily mean energy intake was 2017+/-528 kcal in men (n=123) and 1731+/-451 kcal in women (n=216; p<0.001). Mean protein intake amounted to 1.0 g/kg body weight. Mean BMI was 28.2+/-6.2 kg/m2 (n=341), 14% of seniors had a BMI <22 kg/m2 (including 4% with BMI <20 kg/m2). Critical MUAC (<22 cm) was indicated in 6% of subjects; and CC <31 cm in 11% of men, 21% of women (p<0.05). After adjusting for sex and age, BMI, MUAC and CC were negatively associated with high care level, hospitalization in the previous year, nausea/vomiting, prevalence of dementia, poor appetite, and eating difficulties like dependency, chewing and swallowing problems. CONCLUSION: We recommend to pay special attention to the nutritional status of elderly persons in home-care exhibiting named disease burden. PMID- 26892588 TI - Doxorubicin loaded dual pH- and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications. AB - Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced features for the targeted delivery of DOX molecules via the combination of magnetic targeting, and dual pH- and thermo-responsive behaviour which offers spatial and temporal control over the release of DOX. The iron oxide cores exhibit a superparamagnetic behaviour with a saturation magnetization around 70 emu g(-1). The MNCs contained 8.1 wt% of polymer and exhibit good heating properties in an alternating magnetic field. The drug release experiments confirmed that only a small amount of DOX was released at room temperature and physiological pH, while the highest drug release of 85.2% was obtained after 48 h at acidic tumour pH under hyperthermia conditions (50 degrees C). The drug release kinetic followed Korsmeyer-Peppas model and displayed Fickian diffusion mechanism. From the results obtained it can be concluded that this smart magnetic nanocarrier is promising for applications in multi-modal cancer therapy, to target and efficiently deliver heat and drug specifically to the tumour. PMID- 26892586 TI - Neck Circumference Is Not Associated with Dysphagia but with Undernutrition in Elderly Individuals Requiring Long-term Care. AB - OBJECTIVES: The purpose was to assess the association between neck circumference, dysphagia, and undernutrition in elderly individuals requiring long-term care. DESIGN: Cross-sectional study. SETTING: Geriatric health services facilities, acute hospitals, and the community. PARTICIPANTS: Elderly individuals >=65 years of age with dysphagia or possible dysphagia (N=385). MEASUREMENTS: Neck circumference, the Dysphagia Severity Scale (DSS) and the Mini Nutritional Assessment Short Form (MNA-SF). RESULTS: Participants included 130 males and 255 females with a mean age (+/- standard deviation) of 83 +/- 8.0 years. Sixty-six were in acute hospitals, 195 were in geriatric health services facilities, and 124 were community-dwelling. The mean neck circumference in males and females was 37.1 +/- 3.0 cm and 33.3 +/- 3.3 cm, respectively. Based on the DSS, 81 participants were within normal limits, 137 had dysphagia without aspiration, and 167 had dysphagia with aspiration. The MNA-SF revealed that 173 were malnourished, 172 were at risk of malnutrition, and 40 had a normal nutritional status. Neck circumference was not significantly correlated with the DSS (r= 0.080) but was significantly correlated with the MNA-SF (r=0.183) in the Spearman rank correlation analysis. In the logistic regression, neck circumference was not independently associated with the DSS after adjusting for the MNA-SF, the Barthel Index, age, sex, setting, and cerebrovascular disorders. However, the multiple regression analysis showed that neck circumference had an independent effect on the MNA-SF after adjusting for the Barthel Index, age, sex, setting and cerebrovascular disorders. CONCLUSIONS: Neck circumference is not associated with dysphagia but with undernutrition in elderly individuals requiring long-term care. PMID- 26892590 TI - Traumatic herniation of the buccal fat pad. AB - Traumatic herniation of the buccal fat pad is a rare traumatic disease. Treatment consists of either excision or replacement. We herein report the first case in which a traumatic herniation of the buccal fat pad healed naturally. It was necessary to differentiate the disease from lipoblastoma. A 17-month-old boy was admitted to a clinic with an intraoral tumor that had suddenly increased in size. The tumor was diagnosed as herniation of the buccal fat pad on pathology of a biopsy specimen. In the present case, the escaped buccal fat body returned naturally and engrafted without dysfunction or facial defects. Given that young children may easily fall down with various objects in their mouth, care is required to prevent traumatic accidents. Traumatic herniation of the buccal fat pad should be considered in the differentiation of tumors of the oral cavity in young children. PMID- 26892589 TI - Factors related to breast cancer detection mode and time to diagnosis in Alberta, Canada: a population-based retrospective cohort study. AB - BACKGROUND: Understanding the factors affecting the mode and timeliness of breast cancer diagnosis is important to optimizing patient experiences and outcomes. The purposes of the study were to identify factors related to the length of the diagnostic interval and assess how they vary by mode of diagnosis: screen or symptom detection. METHODS: All female residents of Alberta diagnosed with first primary breast cancer in years 2004-2010 were identified from the Alberta Cancer Registry. Data were linked to Physician Claims and screening program databases. Screen-detected patients were identified as having a screening mammogram within 6 months prior to diagnosis; remaining patients were considered symptom-detected. Separate quantile regression was conducted for each detection mode to assess the relationship between demographic/clinical and healthcare factors. RESULTS: Overall, 38 % of the 12,373 breast cancer cases were screen-detected compared to 47 % of the screen-eligible population. Health region of residence was strongly associated with cancer detection mode. The median diagnostic interval for screen and symptom-detected cancers was 19 and 21 days, respectively. The variation by health region, however, was large ranging from an estimated median of 4 to 37 days for screen-detected patients and from 17 to 33 days for symptom-detected patients. Cancer stage was inversely associated with the diagnostic interval for symptom-detected cancers, but not for screen-detected cancers. CONCLUSION: Significant variation by health region in both the percentage of women with screen-detected cancer and the length of the diagnostic interval for screen and symptom-detected breast cancers suggests there could be important differences in local breast cancer diagnostic care coordination. PMID- 26892594 TI - In this issue of Occupational Medicine. PMID- 26892593 TI - Two stages of directed forgetting: Electrophysiological evidence from a short term memory task. AB - In this study, a short-term memory test was used to investigate the temporal course and neural mechanism of directed forgetting under different memory loads. Within each trial, two memory items with high or low load were presented sequentially, followed by a cue indicating whether the presented items should be remembered. After an interval, subjects were asked to respond to the probe stimuli. The ERPs locked to the cues showed that (a) the effect of cue type was initially observed during the P2 (160-240 ms) time window, with more positive ERPs for remembering relative to forgetting cues; (b) load effects were observed during the N2-P3 (250-500 ms) time window, with more positive ERPs for the high load than low-load condition; (c) the cue effect was also observed during the N2 P3 time window, with more negative ERPs for forgetting versus remembering cues. These results demonstrated that directed forgetting involves two stages: task relevance identification and information discarding. The cue effects during the N2 epoch supported the view that directed forgetting is an active process. PMID- 26892591 TI - Dynamic nuclear polarization-magnetic resonance imaging at low ESR irradiation frequency for ascorbyl free radicals. AB - Highly water-soluble ubiquinone-0 (CoQ0) reacts with ascorbate monoanion (Asc) to mediate the production of ascorbyl free radicals (AFR). Using aqueous reaction mixture of CoQ0 and Asc, we obtained positively enhanced dynamic nuclear polarization (DNP)-magnetic resonance (MR) images of the AFR at low frequency (ranging from 515 to 530 MHz) of electron spin resonance (ESR) irradiation. The shape of the determined DNP spectrum was similar to ESR absorption spectra with doublet spectral peaks. The relative locational relationship of spectral peaks in the DNP spectra between the AFR (520 and 525 MHz), (14)N-labeled carbamoyl-PROXYL ((14)N-CmP) (526.5 MHz), and Oxo63 (522 MHz) was different from that in the X band ESR spectra, but were similar to that in the 300-MHz ESR spectra. The ratio of DNP enhancement to radical concentration for the AFR was higher than those for (14)N-CmP, Oxo63, and flavin semiquinone radicals. The spectroscopic DNP properties observed for the AFR were essentially the same as those for AFR mediated by pyrroloquinoline quinone. Moreover, we made a success of in vivo DNP MR imaging of the CoQ0-mediated AFR which was administered by the subcutaneous and oral injections as an imaging probe. PMID- 26892595 TI - Cognitive enhancers--performance or problem? PMID- 26892596 TI - Psychosocial risk management: calamity or opportunity? PMID- 26892597 TI - Limbourg Brothers, June c.1412-1416. PMID- 26892598 TI - Beck Depression Inventory. PMID- 26892599 TI - A 15-year retrospective analysis of the epidemiology and outcomes for elderly emergency general surgical admissions in the North East of England: A case for multidisciplinary geriatric input. AB - INTRODUCTION: Life expectancies in the UK are increasing and with this there is an increasing elderly population with more complex co-morbidity. Emergency surgery in the elderly is challenging in terms of decision making, managing co morbidity and post-operative rehabilitation with high morbidity and mortality. To optimise service design and development, it is important to understand the changing pattern of emergency surgical care for this group. METHODS: After obtaining necessary approvals, we approached each hospital trust in the North of England for details of every emergency admission under a general surgeon from 2000 to 2014. Data for each admission included demographics, co-morbidities, diagnoses, procedures undertaken and outcomes. RESULTS: There were 105 002 elderly (>=70 years) emergency general surgical admissions, and mean age and co morbidity (defined by Charlson index scores) increased (both p < 0.001). Operative intervention was undertaken in a similar proportion of patients in all age groups (13%), with more patients undergoing operations over time (p < 0.001), of which 50% were within 48 h of admission. Overall in-hospital mortality decreased significantly as did length of hospital stay (both p < 0.001). Factors associated with increased 30 day in-hospital mortality were increasing age and Charlson score, admissions directly from clinic, operations undertaken at the weekend and patients admitted earlier in the study period. CONCLUSION: The workload of emergency general surgery in the elderly is becoming more complex. This challenge is already being addressed with improvements in outcomes. The data presented here reinforces the need for new models of care with increased multidisciplinary geriatric care input into elderly surgical patient care in the perioperative period. PMID- 26892600 TI - DDX3 promotes tumor invasion in colorectal cancer via the CK1epsilon/Dvl2 axis. AB - DDX3, a subunit of CK1epsilon, phosphorylates Dvl2 to promote beta-catenin activation. Overexpression of the Dvl2 protein results in potent activation of beta-catenin/TCF signaling in colorectal cancer. Therefore, we hypothesized that DDX3 might promote tumor invasion via the CK1epsilon/Dvl2 axis due to beta catenin/TCF activation. Western blotting showed that beta-catenin expression was decreased by DDX3 knockdown and increased by DDX3 overexpression in colorectal cancer cells. The TCF promoter activity and invasion capability were concomitantly increased and decreased by DDX3 manipulation in these cells. The invasion capability in colon cancer cells and xenograft lung tumor nodules induced by a DDX3-overexpressing T84 stable clone in tail-vein injection model were nearly suppressed by inhibitors of CK1epsilon (PF4800567) and beta catenin/TCF signaling (XAV939). Among colorectal cancer patients, DDX3 expression was positively correlated with the expression of pDvl2 and nuclear beta-catenin in tumor tissues. The expression of pDvl2 occurred more frequently in high nuclear than in low-nuclear beta-catenin tumors. A prognostic significance of DDX3, pDvl2, and nuclear beta-catenin on overall survival and relapse free survival was observed in this study population. We therefore suggest CK1epsilon or beta-catenin/TCF signaling as potential targets for improving tumor regression and outcomes in colorectal cancer, particularly tumors with high-DDX3/high nuclear beta-catenin or high-DDX3/high-pDvl2/high-nuclear beta-catenin expression. PMID- 26892601 TI - Pathways to Sustainability: 8-Year Follow-Up From the PROSPER Project. AB - The large-scale dissemination of evidence-based practices (EBPs) is often hindered by problems with sustaining initiatives past a period of initial grant funding. Communities often have difficulty generating resources needed to sustain and grow their initiatives, resulting in limited public health impact. The PROSPER project, initiated in 2001, provided community coalitions with intensive technical assistance around marketing, communications, and revenue generating strategies. Past reports from PROSPER have indicated that these coalitions were successful with sustaining their programming, and that sustainability could be predicted by early aspects of team functioning and leadership. The current study examines financial sustainability 8 years following the discontinuation of grant funding, with an emphasis on sources of revenue and the relationships between revenue generation, team functioning, and EBP participation. This study used four waves of data related to resource generation collected between 2004 and 2010 by PROSPER teams in Iowa and Pennsylvania. Teams reported annually on the amount and sources of funding procured, as well as annual reports of team functioning and leadership and annual reports of EBP participation by youth and parents. Data revealed that teams' overall revenue generation increased over time. There was significant variation in success with revenue generation at both the community level and across the two states. Teams accessed a variety of sources. Cash revenue generation was positively and predictively associated with EBP participation, but relationships with team functioning and leadership ratings varied significantly by state. State level differences in in-kind support were also apparent. The results indicated that there are different pathways to sustainability, and that no one method works for all teams. The presence of state level infrastructures available to support prevention appeared to account for significant differences in sustainability success between Pennsylvania and Iowa. PMID- 26892603 TI - Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension. AB - BACKGROUND: Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. RESULTS: Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66 0.95; P = .004). CONCLUSIONS: In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. PMID- 26892602 TI - Physical Activity and Symptoms in Pulmonary Arterial Hypertension. AB - BACKGROUND: Fatigue is a common symptom in patients with pulmonary arterial hypertension (PAH); however, the impact of fatigue on daily physical activity in PAH is unknown. Accelerometry is a validated measure for assessing physical activity. We hypothesized that patients with PAH reporting higher levels of fatigue would have lower daily physical activity measured by accelerometry. METHODS: We performed a prospective cohort study of 15 women with PAH. On day 1, subjects completed the Multidimensional Fatigue Inventory (MFI), the United States Cambridge Pulmonary Hypertension Outcome Review (US CAMPHOR), and a 6-min walk test. Subjects wore the accelerometer on their dominant hip and completed an activity diary for 7 days. On day 15, subjects repeated the MFI and the US CAMPHOR, and then wore the accelerometer and completed an activity diary for an additional 7 days. All multivariate analyses were adjusted for age, BMI, and PAH type. RESULTS: The mean age was 50.5 years, and 53% had idiopathic or heritable PAH. During the 2 weeks, subjects were mostly sedentary (85% of the time), although 10% of their time was spent performing low-level activity. Lower average daily counts were associated with worse self-reported energy levels, whereas less day-to-day physical activity variability was associated with more self-reported mental fatigue, physical fatigue, and total activity. Higher percentage of activity bouts was also associated with worse energy. CONCLUSIONS: Women with PAH may spend most of their time being sedentary, and lower self-reported energy levels are associated with less daily activity. Interventions to improve symptoms such as fatigue may also increase physical activity levels in PAH. PMID- 26892605 TI - Air pollution from traffic and risk for brain tumors: a nationwide study in Denmark. AB - PURPOSE: Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out to replicate that finding in a large nationwide case-control study. METHODS: We identified all 4,183 adult brain tumor cases in Denmark in the years 2000-2009 and 8,018 risk set sampled population controls matched on gender and year of birth. We extracted residential address histories and estimated mean residential nitrogen oxides (NO x ) concentrations since 1971 with a validated dispersion model. Categorical and linear odds ratios (OR) and confidence intervals (CI) were calculated with conditional logistic regression models. RESULTS: The highest risk estimates for any brain cancer were observed among subjects with the highest average exposure levels (80-99 ug/m(3): OR 1.27, 95% CI 0.82-1.96; >=100 ug/m(3): 1.40, 95 % CI 0.87-2.26 as compared to <20 ug/m(3) NO x ), but there was no increased OR at NO x levels below 80 ug/m(3) and when modeled linearly there was no significant association with risk of brain cancer (OR 1.11, 95% CI 0.84-1.46 per 100 ug/m(3) NO x ). In sub-analysis the OR associated with exposures >=100 ug/m(3) was 2.30 (95% CI 1.15-4.59) for non-glioma and 0.89 (95% CI 0.44-1.77) for glioma. CONCLUSIONS: This study did not support the relatively strong linear association between air pollution and risk of brain tumors which was found in our previous study. The suggestion of an increased brain tumor risk at high exposures merits further attention as does the differing results according to tumor morphology. PMID- 26892604 TI - Modeling how substitution of sedentary behavior with standing or physical activity is associated with health-related quality of life in colorectal cancer survivors. AB - PURPOSE: Previous research indicates that sedentary behavior is unfavorably associated with health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Using isotemporal substitution modeling, we studied how substituting sedentary behavior with standing or physical activity was associated with HRQoL in CRC survivors, 2-10 years post-diagnosis. METHODS: A cross-sectional study was conducted in stage I-III CRC survivors (n = 145) diagnosed at Maastricht University Medical Center+, the Netherlands (2002-2010). Sedentary, standing, and physical activity time were measured by the thigh-mounted MOX activity monitor. HRQoL outcomes comprised global quality of life, physical, role, and social functioning, and disability (scales: 0-100), fatigue (20-140), and depression and anxiety (0-21). Isotemporal substitution modeling was applied to analyze associations with HRQoL of substituting sedentary time with equal time in standing or physical activity. RESULTS: On average, participants spent 10.2 h/day sedentary (SD, 1.7), 3.4 h/day standing (1.3), and 1.7 h/day in physical activity (0.8). In confounder-adjusted isotemporal models, substituting sedentary time with standing or with physical activity was associated with significantly better physical functioning (regression coefficient [beta], i.e., difference in outcome score per 1 h/day of sedentary time substituted with standing or physical activity, 3.1; 95% confidence interval [CI] 0.5, 5.7; and 5.6; 0.7, 10.6, respectively). Substituting sedentary time with standing was also associated with significantly lower disability (beta, -3.0; 95% CI -4.9, -1.1) and fatigue (-4.0; -7.6, -0.3). CONCLUSIONS: Our results suggest that substituting sedentary behavior with standing or physical activity may be beneficially associated with certain HRQoL outcomes in CRC survivors. Prospective studies are warranted to confirm whether actual substitution of sedentary behavior with these activities may improve HRQoL in CRC survivors. PMID- 26892606 TI - Erratum to: Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease. PMID- 26892608 TI - Incidence and impact of proxy response in measuring patient experience: secondary analysis of a large postal survey using propensity score matching. AB - OBJECTIVE: To determine whether use of proxy respondents in a patient experience survey was related to patient characteristics, and to compare patient and proxy responses. DESIGN: Secondary analysis, using propensity score matching, of the NHS adult inpatient survey, a large cross-sectional survey. SETTING: Hospitals (n = 161) providing inpatient services in England in 2011. PARTICIPANTS: The survey received 70 863 responses: 10 661 (15.6%) involved proxy respondents in some way. INTERVENTION: None. MAIN OUTCOME MEASURES: Prevalence of proxy response was explored by patient demographic characteristics. Responses were compared using seven composite domains and one overall rating. Cases involving proxy responses were matched to similar independent responses via propensity score matching and mean scores compared using t-tests. RESULTS: Use of proxy respondents was common, with 15.7% of responses involving a proxy in some way: higher than in other similar collections internationally. Proxy response was more common for some patient groups, such as older people and those from black and minority ethnic groups. Reports made by or with the assistance of proxy respondents were markedly less positive than those from patients completing the survey unaided. This pattern was consistent across all tested variables, although the biggest differences were observed for a subjective 'overall rating' question. CONCLUSIONS: The prevalence of proxy response varied according to patient characteristics, but proxies were consistently less positive than patients responding unaided. Possible explanations include genuine differences in care, differential health outcomes or differences in perceptions. Patient experience surveys should collect information on use of proxy respondents to enable more refined analysis. PMID- 26892609 TI - Performance results for a workstation-integrated radiology peer review quality assurance program. AB - OBJECTIVE: To assess review completion rates, RADPEER score distribution, and sources of disagreement when using a workstation-integrated radiology peer review program, and to evaluate radiologist perceptions of the program. DESIGN: Retrospective review of prospectively collected data. SETTING: Large private outpatient radiology practice. PARTICIPANTS: Radiologists (n = 66) with a mean of 16.0 (standard deviation, 9.2) years of experience. INTERVENTIONS: Prior studies and reports of cases being actively reported were randomly selected for peer review using the RADPEER scoring system (a 4-point scale, with a score of 1 indicating agreement and scores of 2-4 indicating increasing levels of disagreement). MAIN OUTCOME MEASURES: Assigned peer review completion rates, review scores, sources of disagreement and radiologist survey responses. RESULTS: Of 31 293 assigned cases, 29 044 (92.8%; 95% CI 92.5-93.1%) were reviewed. Discrepant scores (score = 2, 3 or 4) were given in 0.69% (95% CI 0.60-0.79%) of cases and clinically significant discrepancy (score = 3 or 4) was assigned in 0.42% (95% CI 0.35-0.50%). The most common cause of disagreement was missed diagnosis (75.2%; 95% CI 66.8-82.1%). By anonymous survey, 94% of radiologists felt that peer review was worthwhile, 90% reported that the scores they received were appropriate and 78% felt that the received feedback was valuable. CONCLUSION: Workstation-based peer review can increase completion rates and levels of radiologist acceptance while producing RADPEER scores similar to those previously reported. This approach may be one way to increase radiologist engagement in peer review quality assurance. PMID- 26892607 TI - Overexpression of proteasomal activator PA28alpha serves as a prognostic factor in oral squamous cell carcinoma. AB - BACKGROUND: Despite recent advances in oral squamous cell carcinoma (OSCC) diagnosis and therapy, disease recurrence remains common and is strongly associated with mortality. It is therefore critical to identify new targets for both treatment and diagnostic purposes. We aimed at investigating the role of PA28alpha, a proteasomal activator in OSCC. METHODS: The expression of PA28alpha was examined in a panel of OSCC cell lines and tissues, associated with oncomine analysis. In a large OSCC patient cohort, the prognostic value of PA28alpha expression was evaluated. Primary clinical end points were recurrence-free and overall survival rate. Functional involvement of PA28alpha in OSCC was examined in both in vitro and in vivo models upon specific siRNA knockdown. RESULTS: PA28alpha was found to be overexpressed in OSCC cell lines and tumor tissues. High expression of PA28alpha was significantly associated with recurrence and poorer overall survival. Specific knockdown of PA28alpha inhibited OSCC cell proliferation, migration, invasion in vitro and reduced the growth of OSCC xenografts in vivo. Multivariate Cox regression analyses revealed PA28alpha as independent prognostic predictors. CONCLUSIONS: These results suggest that PA28alpha is involved in OSCC oncogenesis and may serve as a potential prognostic factor. PMID- 26892610 TI - Criteria-based audit of caesarean section in a referral hospital in rural Tanzania. AB - OBJECTIVE: WHO uses the Caesarean section (CS) rate to monitor implementation of emergency obstetric care (EmOC). Although CS rates are rising in sub-Saharan Africa, maternal outcome has not improved. We audited indications for CS and related complications among women with severe maternal morbidity and mortality in a referral hospital in rural Tanzania. METHODS: Cross-sectional study was from November 2009 to November 2011. Women with severe maternal morbidity and mortality were identified and those with CS were included in this audit. Audit criteria were developed based on the literature review and (inter)national guidelines. Tanzanian and Dutch doctors reviewed hospital notes. The main outcome measured was prevalence of substandard quality of care leading to unnecessary CS and delay in performing interventions to prevent CS. RESULTS: A total of 216 maternal near misses and 32 pregnancy-related deaths were identified, of which 82 (33.1%) had a CS. Indication for CS was in accordance with audit criteria for 36 of 82 (44.0%) cases without delay. In 20 of 82 (24.4%) cases, the indication was correct; however, there was significant delay in providing standard obstetric care. In 16 of 82 (19.5%) cases, the indication for CS was not in accordance with audit criteria. During office hours, CS was more often correctly indicated than outside office hours (60.0% vs. 36.0%, P < 0.05). DISCUSSION: Caesarean section rate is not an useful indicator to monitor quality of EmOC as a high rate of unnecessary and potentially preventable CS was identified in this audit. PMID- 26892611 TI - Light-Harvesting Photosensitizers for Photodynamic Inactivation of Bacteria under Both Visible and Near-Infrared Excitations. AB - We report a hybrid singlet oxygen production system, where strong resonance coupling between plasmonic nanoparticles and photosensitizing molecules results in exceptionally high singlet oxygen production under both visible light and near infrared light excitation, even for the photosensitizing molecules without near infrared absorption. The light-harvesting property of the plasmon-photosensitizer hybrids leads to an enhanced, broad-spectrum photodynamic inactivation of bacteria under a wide range of excitations, including that with near-infrared light. PMID- 26892615 TI - Approaching chronic cough. AB - Chronic cough is one of the most common reasons for referral to a respiratory physician. Although fatal complications are rare, it may cause considerable distress in the patient's daily life. Western and local data shows that in patients with a normal chest radiograph, the most common causes are postnasal drip syndrome, postinfectious cough, gastro-oesophageal reflux disease and cough variant asthma. Less common causes are the use of angiotensin-converting enzyme inhibitors, smoker's cough and nonasthmatic eosinophilic bronchitis. A detailed history-taking and physical examination will provide a diagnosis in most patients, even at the primary care level. Some cases may need further investigations or specialist referral for diagnosis. PMID- 26892612 TI - Triple peptide vaccination as consolidation treatment in women affected by ovarian and breast cancer: Clinical and immunological data of a phase I/II clinical trial. AB - Vaccination with priming and expansion of tumour reacting T cells is an important therapeutic option to be used in combination with novel checkpoint inhibitors to increase the specificity of the T cell infiltrate and the efficacy of the treatment. In this phase I/II study, 14 high-risk disease-free ovarian (OC) and breast cancer (BC) patients after completion of standard therapies were vaccinated with MUC1, ErbB2 and carcinoembryonic antigen (CEA) HLA-A2+-restricted peptides and Montanide. Patients were subjected to 6 doses of vaccine every two weeks and a recall dose after 3 months. ECOG grade 2 toxicity was observed at the injection site. Eight out of 14 patients showed specific CD8+ T cells to at least one antigen. None of 4 patients vaccinated for compassionate use showed a CD8 activation. An OC patient who suffered from a lymph nodal recurrence, showed specific anti-ErbB2 CD8+ T cells in the bulky aortic lymph nodes suggesting homing of the activated T cells. Results confirm that peptide vaccination strategy is feasible, safe and well tolerated. In particular OC patients appear to show a higher response rate compared to BC patients. Vaccination generates a long-lasting immune response, which is strongly enhanced by recall administrations. The clinical outcome of patients enrolled in the trial appears favourable, having registered no deceased patients with a minimum follow-up of 8 years. These promising data, in line with the results of similar studies, the high compliance of patients observed and the favourable toxicity profile, support future trials of peptide vaccination in clinically disease-free patients who have completed standard treatments. PMID- 26892617 TI - Erratum to: Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling. PMID- 26892616 TI - Molecular detection and prevalence of Giardia duodenalis and Cryptosporidium spp. among long-tailed macaques (Macaca fascicularis) in Thailand. AB - Giardia duodenalis and Cryptosporidium spp. are divergent protozoal intestinal parasites that infect human beings and other animals, including non-human primates. Although long-tailed macaques (Macaca fascicularis) reside in human communities in Thailand, the prevalence of Giardia spp. and Cryptosporidium spp. in these primates has not been previously investigated. The objective of this study was to evaluate long-tailed macaques living near human communities as possible hosts of these intestinal parasites. In 2014, 200 fecal samples were randomly collected from long-tailed macaques living in different areas of Lopburi province, Thailand, and tested with a panel of PCR assays for Giardia spp. and Cryptosporidium spp. G. duodenalis assemblage B was most frequently detected (6%), while assemblage A and an inconclusive assemblage were detected in single samples, for a total G. duodenalis infection rate of 7%. Two samples (1%) tested positive for Cryptosporidium spp., which were both classified as monkey genotypes. No significant associations were found between G. duodenalis infection and sex or location of macaques. This study indicates that long-tailed macaques can carry G. duodenalis and, to a lesser extent, Cryptosporidium spp. monkey genotype. These results warrant education of residents and tourists to limit contact with long-tailed macaques and to take hygienic precautions to mitigate risk of zoonotic and anthroponotic transmission of these parasites between people and macaques. PMID- 26892618 TI - Relationship between fracture of mandibular condyle and absence of unerupted mandibular third molar-a retrospective study. AB - PURPOSE: The purpose of the present study was to find, if there exists, a co relation between presence of unerupted mandibular third molar and fracture of mandibular condyle. METHODS: A retrospective, multicenter study was done collecting the data of all mandibular condyle fractures treated from November 2006 till August 2015. Data was collected from the patient's records and radiographs for the following information: age, sex, etiology of fracture, presence and state of lower third molars, and associated fracture. The results were subjected to statistical analysis. RESULTS: Out of 180 patients of condylar fracture, unerupted third molars were present in 35 (19.44 %) cases compared to 145 (80.55 %) cases of condylar fracture where the unerupted third molars were not present. The difference was statistically significant (p < 0.05). In the unerupted third molar present group, isolated bilateral condylar fracture was seen in 4 (11.4 %) cases, bilateral condylar fracture associated with other mandibular fractures in 9 (25.7 %) cases, isolated unilateral condylar fracture in 0 (0.0 %) cases, and unilateral condylar fracture associated with other mandibular fractures in 17 (48.5 %) cases and condylar fracture associated with mid face fractures in 5 (14.2 %) cases. In the unerupted third molar absent group, isolated bilateral condylar fracture was seen in 5 (3.4 %) cases, bilateral condylar fracture associated with other mandibular fractures in 30 (20.6 %) cases, isolated unilateral condylar fracture in 24 (16.5 %) cases, unilateral condylar fracture associated with other mandibular fractures in 73 (50.34 %) cases, and condylar fracture associated with mid face fractures in 13(8.96 %) cases. The difference between the groups was statistically significant (p = 0.032). CONCLUSION: This study suggests that the fractures of mandibular condylar region have a significantly higher incidence in patients without an unerupted mandibular third molar. PMID- 26892619 TI - Trastuzumab in the Treatment of Breast Cancer. AB - Breast cancer (BC) is the most common cancer in women worldwide, and has an undeniable negative impact on public health. The advent of molecular biology and immunotherapy has made targeted therapeutic interventions possible, providing treatments tailored to the individual characteristics of the patient and the disease. The over-expression of human epidermal growth factor receptor (HER) 2 is implicated in the pathophysiology of BC and represents a clinically relevant biomarker for its treatment. Trastuzumab, a recombinant antibody targeting HER2, was the first biological drug approved for the treatment of HER2-positive BC. Although there are currently other anti-HER2 agents available (e.g. pertuzumab and lapatinib), trastuzumab remains the gold standard for treatment of this disease subtype. Nonetheless, concerns have been raised regarding potential cardiotoxicity and treatment resistance. Moreover, several other therapeutic issues remain unclear and have been addressed in an inconsistent way. The current literature lacks a comprehensive review of trastuzumab providing useful information for clinical practice, including pharmacokinetic and pharmacodynamic aspects, its clinical use, existing controversies and future advances. This detailed review of trastuzumab in the pharmacotherapy of BC attempts to fill this gap. PMID- 26892620 TI - [Paravertebral block for management of acute postoperative pain and intercostobrachial neuralgia in major breast surgery]. AB - BACKGROUND: Several locoregional techniques have been described for the management of acute and chronic pain after breast surgery. The optimal technique should be easy to perform, reproducible, with little discomfort to the patient, little complications, allowing good control of acute pain and a decreased incidence of chronic pain, namely intercostobrachial neuralgia for being the most frequent entity. OBJECTIVES: The aim of this study was to evaluate the paravertebral block with preoperative single needle prick for major breast surgery and assess initially the control of postoperative nausea and vomiting (PONV) and acute pain in the first 24hours and secondly the incidence of neuropathic pain in the intercostobrachial nerve region six months after surgery. METHODS: The study included 80 female patients, ASA I-II, aged 18-70 years, undergoing major breast surgery, under general anesthesia, stratified into 2 groups: general anesthesia (inhalation anesthesia with opioids, according to hemodynamic response) and paravertebral (paravertebral block with single needle prick in T4 with 0.5% ropivacaine + adrenaline 3MUg/mL with a volume of 0.3mL/kg preoperatively and subsequent induction and maintenance with general inhalational anesthesia). In the early postoperative period, patient-controlled analgesia (PCA) was placed with morphine set for bolus on demand for 24hours. Intraoperative fentanyl, postoperative morphine consumption, technique-related complications, pain at rest and during movement were recorded at 0h, 1h, 6h and 24h, as well as episodes of PONV. All variables identified as factors contributing to pain chronicity age, type of surgery, anxiety according to the Hospital Anxiety and Depression Scale (HADS), preoperative pain, monitoring at home; body mass index (BMI) and adjuvant chemotherapy/radiation therapy were analyzed, checking the homogeneity of the samples. Six months after surgery, the incidence of neuropathic pain in the intercostobrachial nerve was assessed using the DN4 scale. RESULTS: The Visual Analogue Scale (VAS) values of paravertebral group at rest were lower throughout the 24hours of study 0h 1.90 (+/- 2.59) versus 0.88 (+/- 1.5) 1h 2.23 (+/- 2.2) versus 1.53 (+/- 1.8) 6h 1.15 (+/- 1.3) versus 0.35 (+/- 0.8); 24h 0.55 (+/- 0.9) versus 0.25 (+/- 0.8) with statistical significance at 0h and 6h. Regarding movement, paravertebral group had VAS values lower and statistically significant in all four time points: 0h 2.95 (+/- 3.1) versus 1.55 (+/- 2.1); 1h 3.90 (+/- 2.7) versus 2.43 (+/- 1.9) 6h 2.75 (+/- 2.2) versus 1.68 (+/- 1.5); 24h 2.43 (+/- 2.4) versus 1.00 (+/- 1.4). The paravertebral group consumed less postoperative fentanyl (2.38+/-0.81MUg/kg versus 3.51+/-0.81MUg/kg) and morphine (3.5mg+/-3.4 versus 7mg+/-6.4) with statistically significant difference. Chronic pain evaluation of at 6 months of paravertebral group found fewer cases of neuropathic pain in the intercostobrachial nerve region (3 cases versus 7 cases), although not statistically significant. CONCLUSIONS: Single-injection paravertebral block allows proper control of acute pain with less intraoperative and postoperative consumption of opioids but apparently it cannot prevent pain chronicity. Further studies are needed to clarify the role of paravertebral block in pain chronicity in major breast surgery. PMID- 26892621 TI - NICE calls for more research on ELISA tests for Crohn's disease. PMID- 26892624 TI - Corrigendum. PMID- 26892623 TI - Adolescent self-harm in the community: an update on prevalence using a self report survey of adolescents aged 13-18 in England. AB - Background: To establish an estimate of prevalence in a nationally representative sample of community adolescents. To examine associations between self-harm and wellbeing. Methods: An anonymous self-report survey completed by 2000 adolescents aged 13-18 years across England. Wellbeing was measured using the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS). Results: In total 15.5% (n = 309) of participants reported ever having self-harmed (95% confidence intervals 13.9 17.1). The median age of onset was 13.0 years. Females aged 13-15 years reported the highest incidence of self-harm within the past year (54.9%). Cutting elsewhere (other than on the arms) was more prevalent amongst females (56.4%). The mean wellbeing score for the whole sample (45.6) was lower than the WEMWBS validation score (48.8). Self-harm was associated with a significantly lower wellbeing score, with mean scores of 38.7 (ever self-harmed) and 46.8 (never self harmed). Conclusions: Self-harm remains prevalent amongst adolescents aged 13-18 years in England. An awareness of the age of peak incidence and risks associated with preferred harming behaviours is crucial during assessment and intervention. The promotion of wellbeing is important for all young people. Further study is needed on the ways in which wellbeing may prevent, or ameliorate, the distress associated with self-harm. PMID- 26892622 TI - Increased Antiretroviral Therapy Use and Virologic Suppression in the Bronx in the Context of Multiple HIV Prevention Strategies. AB - Multiple population-based HIV prevention strategies from national, state, local, and institutional levels have been implemented in the Bronx, which has one of the highest HIV prevalences in the U.S. We examined changes in antiretroviral therapy (ART) use and associated outcomes between 2007 and 2014 among patients seen at one of >20 outpatient clinics affiliated with the largest Bronx HIV care provider. Among eligible HIV-infected patients age >=13 years, we examined annual trends in ART use, mean HIV RNA level, and virologic suppression (<200 copies/ml) overall and among prespecified subgroups. In a subset with suppressed HIV RNA at the end of each year, we determined the percentage whose levels remained suppressed within the next year. Regression models assessed disparities in outcomes. Among 7,196 patients (median age 50, 47% Hispanic, 45% black), we identified consistent increases over time in the percent prescribed ART (78% in 2007 to 93% in 2014) and with virologic suppression (58% to 80%), as mean HIV RNA decreased (351 to 73 copies/ml) (all p < .001). Sustained virologic suppression improved markedly beginning in 2011, coinciding with local test-and-treat initiatives and adoption of expanded treatment guidelines. While disparities among population groups were most pronounced for sustained virologic suppression, those aged 13-24 fared relatively poorly for all outcomes examined (e.g., rate ratio 0.57 for virologic suppression, 95% confidence interval 0.52-0.62, vs. age 65+). Population-wide HIV prevention strategies coincided with improvements in virologic suppression among most population groups. However, more attention is needed to address continued disparities in the HIV care continuum among young people. PMID- 26892625 TI - Presence of antidrug antibodies correlates inversely with the plasma tumor necrosis factor (TNF)-alpha level and the efficacy of TNF-inhibitor therapy in psoriasis. AB - Antidrug antibodies have been shown to be associated with a loss of response during biologic therapy. Despite the potential association, there has been no report on the simultaneous monitoring of the following parameters in psoriasis: presence of neutralizing antibodies, plasma tumor necrosis factor (TNF)-alpha concentration, TNFi concentration and disease activity. Plasma concentrations of adalimumab, infliximab, etanercept and their respective antidrug antibodies, as well as plasma concentrations of TNF-alpha were measured in 77 psoriasis patients receiving biologic therapy, and the values were correlated with the clinical activity of the skin disease. Antidrug antibodies were identified in the plasma of 25% of infliximab-treated patients and 29.6% of adalimumab-treated patients, but not in the etanercept group. Clinical severity scores were significantly higher in the antibody-positive patients. In patients receiving infliximab or adalimumab therapy, the presence of antidrug antibodies was directly associated with reduced plasma TNF-inhibitor concentration and elevated plasma TNF-alpha level. PMID- 26892626 TI - Clearance of Damaged Mitochondria Through PINK1 Stabilization by JNK and ERK MAPK Signaling in Chlorpyrifos-Treated Neuroblastoma Cells. AB - Mitochondrial quality control and clearance of damaged mitochondria through mitophagy are important cellular activities. Studies have shown that PTEN-induced putative protein kinase 1 (PINK1) and Parkin play central roles in triggering mitophagy; however, little is known regarding the mechanism by which PINK1 modulates mitophagy in response to reactive oxygen species (ROS)-induced stress. In this study, chlorpyrifos (CPF)-induced ROS caused mitochondrial damage and subsequent engulfing of mitochondria in double-membrane autophagic vesicles, indicating that clearance of damaged mitochondria is due to mitophagy. CPF treatment resulted in PINK1 stabilization on the outer mitochondrial membrane and subsequently increased Parkin recruitment from the cytosol to the abnormal mitochondria. We found that PINK1 physically interacts with Parkin in the mitochondria of CPF-treated cells. Furthermore, a knockdown of PINK1 strongly inhibited the LC3-II protein level by blocking Parkin recruitment. This indicates that CPF-induced mitophagy is due to PINK1 stabilization in mitochondria. We observed that PINK1 stabilization was selectively regulated by ROS-mediated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling activation but not p38 signaling. In the mitochondria of CPF-exposed cells, pretreatment with specific inhibitors of JNK and ERK1/2 significantly decreased PINK1 stabilization and Parkin recruitment and blocked the LC3-II protein level. Specifically, JNK and ERK1/2 inhibition also dramatically blocked the interaction between PINK1 and Parkin. Our results demonstrated that PINK1 regulation plays a critical role in CPF-induced mitophagy. The simple interpretation of these results is that JNK and ERK1/2 signaling regulates PINK1/Parkin-dependent mitophagy in the mitochondria of CPF-treated cells. Overall, this study proposes a novel molecular regulatory mechanism of PINK1 stabilization under CPF exposure. PMID- 26892628 TI - Factors associated with poor quality of life among Iranian infertile women undergoing IVF. AB - Infertility is a medical and social condition and has a considerable impact on a person's quality of life (QoL). The aim of the study was to determine the QoL of women with fertility problem, and identify factors associated with poor QoL. This cross-sectional study included 155 women with fertility problems undergoing IVF in a referral fertility center in Tehran, Iran. The Fertility Quality of Life, the Hospital Anxiety and Depression Scale and demographic and fertility information questionnaire were administered to all women. The mean total QoL score was 62.57 +/- 16.89. Multivariate analysis showed that the anxiety (beta = 1.59, p < 0.001) and depression (beta = -2.09, p < 0.001) had a negative impact on QoL. Cause of infertility and failure in previous treatment were also significant factors of poorer QoL. The findings indicate that the QoL was worse in women with high depression and anxiety level, failure in previous treatment and unknown cause of infertility. Thus, a comprehensive approach, including psychosocial interventions and support, is absolutely essential to improve the QoL in these women. PMID- 26892630 TI - The microscopic structure of mono-disperse granular heaps and sediments of particles on inclined surfaces. AB - Granular heaps of particles created by deposition of mono-disperse particles raining from an extended source of finite size are characterized by a non homogeneous field of density. It was speculated that this inhomogeneity is due to the transient shape of the sediment during the process of construction of the heap, thus reflecting the history of the creation of the heap. By comparison of structural characteristics of the heap with sediments created on top of inclined planes exploiting the method of Minkowski tensors, we provide further evidence to support this hypothesis. Moreover, for the case of sediments generated by homogeneous rain on surfaces, we provide relationships between the inclination of the surface and the Minkowski measures characterizing the isotropy of local particle environments. PMID- 26892629 TI - The Association Between Circulating Levels of miRNA-181a and Pancreatic Beta Cells Dysfunction via SMAD7 in Type 1 Diabetic Children and Adolescents. AB - BACKGROUND: miRNA-181a has been implicated in autoimmunity and apoptosis. Therefore, this study was conducted to explore its possible role in pancreatic beta-cells dysfunction. METHODS: miRNA-181a expression was evaluated by real-time PCR in serum of 40 type 1 diabetic children and adolescents and 40 age- and gender-matched healthy controls. RESULTS: miRNA-181a expression was significantly higher in diabetic children and adolescents and it was negatively correlated to fasting C-peptide and SMAD7 levels. CONCLUSION: miRNA-181a appears to play a potential role in pancreatic beta-cells dysfunction via SMAD7. PMID- 26892631 TI - Double- and triple-hit lymphomas can present with features suggestive of immaturity, including TdT expression, and create diagnostic challenges. AB - Double- and triple-hit lymphomas (DHL/THL) are aggressive B-cell neoplasms characterized by translocation of MYC with concurrent BCL2 and/or BCL6 translocation. In this retrospective study from one institution, we report clinicopathologic features of 13 cases (9 DHL/4 THL). The median age was 59 years (range 30-74) and patients included eight females and five males. Presentation included enlarging lymphadenopathy/masses (11 patients) and abnormal peripheral blood findings (2 patients). Features which raised the differential of an immature neoplasm included terminal deoxynucleotidyl transferase positivity (four cases, two THL/two DHL); dim CD45 expression (seven cases), lack of CD20 (two cases), or lack of surface immunoglobulin light chain (three cases) by flow cytometry; and blastoid morphology (two cases). We conclude that expression of TdT in a B-cell lymphoma with mature features or expression of surface light chain in a case otherwise suggestive of B-lymphoblastic leukemia/lymphoma should prompt an expedited evaluation for DHL/THL. PMID- 26892627 TI - Revisiting Mitochondrial Function and Metabolism in Pluripotent Stem Cells: Where Do We Stand in Neurological Diseases? AB - Pluripotent stem cells (PSCs) are powerful cellular tools that can generate all the different cell types of the body, and thus overcome the often limited access to human disease tissues; this becomes highly relevant when aiming to investigate cellular (dys)function in diseases affecting the central nervous system. Recent studies have demonstrated that PSC and differentiated cells show altered mitochondrial function and metabolic profiles and production of reactive oxygen species. This raises an emerging paradigm about the role of mitochondria in stem cell biology and urges the need to identify mitochondrial pathways involved in these processes. In this respect, this review focuses on the metabolic profile of PSC and how mitochondrial function can influence the reprogramming and differentiation processes. Indeed, both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) favor the glycolytic pathway as a major source of energy production over oxidative phosphorylation. PSC mitochondria are characterized by a spherical shape, low copy number of mitochondrial DNA, and a hyperpolarized state. Indeed, mitochondria appear to have a crucial role in reprogramming iPSC, in the maintenance of a pluripotent state, and in differentiation. Moreover, an increase in mitochondrial oxidative phosphorylation has to occur for differentiation to succeed. Therefore, in vitro differentiation of neural stem cells (NSCs) into neurons can be compromised if those mechanisms are impaired. Future research should shed light on how mitochondrial impairment occurring in pre differentiation neural stages (e.g., in NSC or premature neurons) may contribute for the etiopathogenesis of neurodevelopmental and neurological disorders. PMID- 26892632 TI - Surveying End-of-Life Medical Decisions in France: Evaluation of an Innovative Mixed-Mode Data Collection Strategy. AB - BACKGROUND: Monitoring medical decisions at the end of life has become an important issue in many societies. Built on previous European experiences, the survey and project Fin de Vie en France ("End of Life in France," or EOLF) was conducted in 2010 to provide an overview of medical end-of-life decisions in France. OBJECTIVE: To describe the methodology of EOLF and evaluate the effects of design innovations on data quality. METHODS: EOLF used a mixed-mode data collection strategy (paper and Internet) along with follow-up campaigns that employed various contact modes (paper and telephone), all of which were gathered from various institutions (research team, hospital, and medical authorities at the regional level). A telephone nonresponse survey was also used. Through descriptive statistics and multivariate logistic regressions, these innovations were assessed in terms of their effects on the response rate, quality of the sample, and differences between Web-based and paper questionnaires. RESULTS: The participation rate was 40.0% (n=5217). The respondent sample was very close to the sampling frame. The Web-based questionnaires represented only 26.8% of the questionnaires, and the Web-based secured procedure led to limitations in data management. The follow-up campaigns had a strong effect on participation, especially for paper questionnaires. With higher participation rates (63.21% and 63.74%), the telephone follow-up and nonresponse surveys showed that only a very low proportion of physicians refused to participate because of the topic or the absence of financial incentive. A multivariate analysis showed that physicians who answered on the Internet reported less medication to hasten death, and that they more often took no medical decisions in the end-of-life process. CONCLUSIONS: Varying contact modes is a useful strategy. Using a mixed-mode design is interesting, but selection and measurement effects must be studied further in this sensitive field. PMID- 26892633 TI - A comparison of endothelial and penetrating keratoplasty outcomes following failed penetrating keratoplasty: a registry study. AB - PURPOSE: To compare graft survival and visual outcomes for endothelial keratoplasty (EK) after a first penetrating keratoplasty (PK), with outcomes of repeat PK after a first PK. METHODS: 400 eyes with a second graft (65 EKs, 335 PKs) performed after failure of a primary PK were identified through the Australian Corneal Graft Registry, a national prospectively followed cohort. Grafts were performed after January 2008 (follow-up of the second graft extending to 6.75 years maximum). Kaplan-Meier graft survival plots were constructed and Cox proportional hazards regression was used to identify independent risk factors for graft failure. Best-corrected Snellen visual acuity (BCVA) at last follow-up was compared with pregraft acuity. RESULTS: Poor Kaplan-Meier graft survival was observed for PK-EK compared with PK-PK (log-rank=29.66, p<0.001). Variables retained in multivariate analysis as significantly influencing survival of the second graft included graft type (PK-EK or PK-PK, p<0.001), length of survival of the previous PK (global p=0.011), graft era (global p=0.018), occurrence of rejection in the second graft (p=0.005) and a history of raised intraocular pressure at any time (p=0.048), but not indication for the first graft. BCVA improved in the majority of surviving grafts and attainment of 6/12 vision was similar for both PK-EK and PK-PK groups. CONCLUSIONS: Our registry findings suggest that repeat PK may deliver a better outcome in terms of graft survival than EK after a failed PK that was performed initially for keratoconus or pseudophakic bullous keratopathy. For surviving grafts, visual outcomes appeared equivalent across groups. PMID- 26892634 TI - Intraoperative aberrometry-based aphakia refraction in patients with cataract: status and options. AB - AIM: To explore the application of intraoperative wavefront aberrometry (IWA) for aphakia-based biometry using three existing formulae derived from autorefractive retinoscopy and introducing new improved formulae. METHODS: In 74 patients undergoing cataract surgery, three repeated measurements of aphakic spherical equivalent (SE) were taken. All measurements were objectively graded for their quality and evaluated with the 'limits of agreement' approach. ORs were calculated and analysis of variance was applied. The intraocular lens (IOL) power that would have given the target refraction was back-calculated from manifest refraction at 3 months postoperatively. Regression analysis was performed to generate two aphakic SE-based formulae for predicting this IOL. The accuracy of the formulae was determined by comparing them to conventional biometry and published aphakia formulae. RESULTS: In 32 eyes, three consecutive aphakic measurements were successful. Objective parameters of IWA map quality significantly impacted measurement variability (p<0.05). The limits of agreement of repeated aphakic SE readings were +0.66 dioptre (D) and -0.69 D. Intraoperative biometry by our formula resulted in 25% and 53% of all cases +/ 0.50D and +/-1.00 D within SE target, respectively. A second formula that took axial length (AL) into account resulted in improved ratios of 41% and 70%, respectively. CONCLUSIONS: A reliable application of IWA to calculate IOL power during routine cataract surgery may not be feasible given the high rate of measurement failures and the large variations of the readings. To enable reliable IOL calculation from IWA, measurement precision must be improved and aphakic IOL formulae need to be fine-tuned. PMID- 26892635 TI - Whole genome characterization of a chelonian orthoreovirus strain identifies significant genetic diversity and may classify reptile orthoreoviruses into distinct species. AB - In this study we report the sequence and phylogenetic characterization of an orthoreovirus strain, CH1197/96, isolated from a spur-thighed tortoise (Testudo graeca) on chicken embryo fibroblast cells. The 23,957 bp long genome sequence was obtained by combined use of semiconductor and capillary sequencing. Although the genomic characterization showed that the virus was most similar to the bush viper reovirus strain, 47/02, and in phylogenies performed with all segments the two strains formed a monophyletic group, the nucleotide (48.4-70.3%) and amino acid (39.2-80.7%) sequence identity values were moderate between the two reptile origin reoviruses. Based on our results and existing classification criteria for the genus Orthoreovirus, the tortoise reovirus strain CH1197/96 might be the first representative of a novel reptilian origin Orthoreovirus species. PMID- 26892636 TI - Cross-Cultural Validation of the Basic Psychological Needs in Physical Education Scale between Portugal and Brazil Samples. AB - The main propose of this study is the cross-cultural validation of the Basic Psychological Needs in Physical Education Scale among Portugal and Brazil samples, through the study of measurement model invariance. Participated in this study, two independent samples, one with 616 Portuguese students, of the 2nd and 3rd basic grade of public school, aged between 9 and 18 years old and another with 450 Brazilian students, from 1st, 2nd and 3rd middle grade of public and private school, aged between 14 and 18 years old. The results support the suitability of the model (three factors, each one with four items), showing an adequate fit to the data in each sample (Portugal: chi2 = 203.8, p = .001, df = 51, SRMR = .062, NNFI = .926, CFI = .943, RMSEA = .070, RMSEA 90% IC = .060-.080; Brazil: chi2 = 173.7, p = .001, df = 51, SRMR = .052, NNFI = .940, CFI = .954, RMSEA = .073, RMSEA 90% IC = .061-.085), as well valid cross-cultural invariance among Portuguese e Brazilian samples (?CFI <= .01). Those findings allow us to conclude that scale can be used to measure the basic psychological needs in physical education in Portugal and in Brazil. PMID- 26892638 TI - Uptake calibration of polymer-based passive samplers for monitoring priority and emerging organic non-polar pollutants in WWTP effluents. AB - The uptake calibration of more than 12 non-polar organic contaminants by 3 polymeric materials is shown: bare polydimetilsiloxane (PDMS, stir-bars), polyethersulfone tubes and membranes (PES) and polyoxymethylene membranes (POM), both in their free form and membrane-enclosed sorptive coating (MESCO). The calibration process was carried out exposing the samplers to a continuous flow of contaminated water at 100 ng mL(-1) for up to 28 days, and, consequently, the sampling rates (Rs, mL day(-1)) of several organic microcontaminants were provided for the first time. In situ Rs values were also determined disposing the samplers in the effluent of a wastewater treatment plant. Finally, these passive samplers were applied to monitor the effluents of two wastewater treatment plants. This application lead to the confirmation of the presence of galaxolide, tonalide and 4-tert-octylphenol at high ng mL(-1) levels, as well as the identification of compounds like some phthalates and alkylphenols at levels below the detection limits for active sampling methods. PMID- 26892637 TI - Antibiotic binding of STY3178, a yfdX protein from Salmonella Typhi. AB - The yfdX family proteins are known for long time to occur in various virulent bacteria including their multidrug resistant (MDR) strains, without any direct assigned function for them. However, yfdX protein along with other proteins involved in acid tolerance response is reported to be up regulated by the multidrug response regulatory system in E. coli. Hence, molecular and functional characterization of this protein is important for understanding of key cellular processes in bacterial cells. Here we study STY3178, a yfdX protein from a MDR strain of typhoid fever causing Salmonella Typhi. Our experimental results indicate that STY3178 is a helical protein existing in a trimeric oligomerization state in solution. We also observe many small antibiotics, like ciprofloxacin, rifampin and ampicillin viably interact with this protein. The dissociation constants from the quenching of steady state fluorescence and isothermal titration calorimetry show that ciprofloxacin binding is stronger than rifampin followed by ampicillin. PMID- 26892640 TI - A microarray-based approach to evaluate the functional significance of protein binding motifs. AB - Intracellular proteins comprise numerous peptide motifs that interact with protein-binding domains. However, using sequence information alone, the identification of functionally relevant interaction motifs remains a challenge. Here, we present a microarray-based approach for the evaluation of peptides as protein-binding motifs. To this end, peptides corresponding to protein interaction motifs were spotted as a microarray. First, peptides were titrated with a pan-specific binder and the apparent K(d) value of this binder for each peptide was determined. For phosphotyrosine-containing peptides, an anti phosphotyrosine antibody was employed. Then, in the presence of the pan-specific binder, arrays were competitively titrated with cell lysate and competition constants were determined. Using the Cheng-Prusoff equation, binding constants for the pan-specific binder and inhibition constants for the lysates were converted into affinity constants for the lysate. We experimentally validate this method using a phosphotyrosine-binding SH2 domain as a further reference. Furthermore, strong binders correlated with binding motifs engaging in numerous interactions as predicted by Scansite. This method provides a highly parallel and robust approach to identify peptides corresponding to interaction motifs with strong binding capacity for proteins in the cell lysate. PMID- 26892641 TI - Development of a monoclonal antibody-based enzyme-linked immunosorbent assay for luteoloside detection in Flos Lonicerae Japonicae. AB - Flos Lonicerae Japonicae (FLJ), the flower bud of Lonicera japonica Thunb. (Caprifoliaceae), is a widely used traditional Chinese medicine with various pharmacological activities. Luteoloside is a major active compound and a quality control marker of FLJ. Luteolin-7-O-glucuronide (LG), an analog of luteoloside, was conjugated with bovine serum albumin (BSA) and ovalbumin (OVA) to create the immunogen and coating antigen, respectively. A sensitive and specific monoclonal antibody (mAb), designated as mAb3A4, was generated with LG-BSA. To screen the authenticity and quality of FLJ, an indirect competitive enzyme-linked immunosorbent assay (icELISA) was established. The concentration of luteoloside producing 50 % inhibition and the working range of the icELISA were 42.3 and 9.1 258.1 MUg L(-1), respectively. The icELISA showed cross-reactivity values of 2414, 402, 230, and <1 % for LG, baicalin, scutellarin, and other analogs of luteoloside, respectively. The average recovery of luteoloside in the FLJ samples as determined by icELISA ranged from 83.0 to 112.5 %. The luteoloside content was determined for different Lonicera herbal samples with icELISA, and the results were confirmed by high-performance liquid chromatography analysis. Thus, this icELISA is suitable for the quality assurance of FLJ samples. Graphical abstract Specific monoclonal antibody-based enzyme-linked immunosorbent assay for luteoloside. PMID- 26892642 TI - Exploration for an Algorithm for Deintensification to Exclude the Retropharyngeal Site From Advanced Oropharyngeal Squamous Cell Carcinoma Treatment. AB - IMPORTANCE: Understanding the drainage patterns to the retropharyngeal lymph nodes is an important consideration in oropharyngeal squamous cell carcinoma (OPSCC) because treatment of these nodes is related to increased morbidity. Prediction of these drainage patterns could not only help minimize treatment morbidity but also prevent failures in at-risk patients as deintensification trials are under way for this disease. OBJECTIVE: To evaluate the prevalence of pathologic retropharyngeal adenopathy (RPA) in OPSCC relative to involvement of the oropharyngeal subsite, number of metastatic neck nodes, T classification, and N classification. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review from January 1, 2003, through December 31, 2010, at an academic referral center of 205 previously untreated patients with pathologically confirmed, advanced-stage (III, IV) OPSCC. Data analysis was performed from January 1, 2013, through June 30, 2015. EXPOSURE: Concurrent chemoradiotherapy. MAIN OUTCOMES AND MEASURES: Radiologic evidence of pathologic RPA was tabulated and related to involvement of the oropharyngeal subsite, number of metastatic neck nodes, T classification, and N classification. RESULTS: Of the 205 previously untreated patients (183 men; mean age, 56.1 years), pathologic RPA was identified in 37 (18.0%) of the 205 patients. Pathologic retropharyngeal lymph nodes were found in 12 (13.5%) of 89 patients with base of tongue cancers, 24 (22.0%) of 109 patients with tonsil cancers, and 1 (14.3%) of 7 patients with other oropharyngeal subsite cancers. Increasing prevalence of RPA was positively correlated with closer proximity to the posterior tonsillar pillar. A multivariable logistic regression model using the oropharyngeal subsite, involvement of the posterior tonsillar pillar, number of metastatic neck nodes, T classification, and N classification revealed that the number of metastatic neck nodes was statistically significant (odds ratio, 1.44; 95% CI, 1.20-1.71; P < .001). CONCLUSIONS AND RELEVANCE: The prevalence of pathologic RPA in this cohort was 18.0%, and patients with multiple nodes had the highest risk of pathologic RPA, followed by involvement of the posterior tonsillar pillar. However, these data suggest that there is no clear algorithm that can be used for deintensification to exclude the retropharyngeal site from the treatment volume using extent of disease gathered from pretreatment imaging for patients with advanced-stage OPSCC. PMID- 26892643 TI - Behavioral outcomes of picky eating in childhood: a prospective study in the general population. AB - BACKGROUND: Picky eaters in the general population form a heterogeneous group. It is important to differentiate between children with transient picky eating (PE) and persistent PE behavior when adverse outcomes are studied. We analyzed four PE trajectories to determine the associations with child mental health prospectively. METHODS: From a population-based cohort, 3,748 participants were assessed for PE at 1.5, 3, and 6 years of age using maternal reports. Four trajectories were defined: persistent (PE at all ages); remitting (PE before 6 years only); late-onset (PE at 6 years only); and never (no PE at any assessment). Child's problem behaviors were assessed with the Teacher's Report Form at 7 years of age. We examined associations between picky eating trajectories and emotional problems, behavioral problems and pervasive developmental problems using logistic regressions. Analyses were adjusted for child, parental, and socioeconomic confounders. We also adjusted for maternal reported baseline problem behavior at age 1.5 years; the never picky eating group was used as reference. RESULTS: Persisting PE predicted pervasive developmental problems at age 7 years (OR = 2.00, 95% CI: 1.10-3.63). The association remained when adjusted for baseline pervasive developmental problems at 1.5 years (OR = 1.96, 95% CI: 1.10-3.51). Persistent PE was not associated with behavioral (OR = 0.92, 95% CI: 0.53-1.60) or emotional problems (OR = 1.24, 95% CI: 0.74-2.07). Other PE trajectories were not related to child behavioral or emotional problems. CONCLUSIONS: Persistent PE may be a symptom or sign of pervasive developmental problems, but is not predictive of other behavioral problems. Remitting PE was not associated with adverse mental health outcomes, which further indicates that it may be part of normal development. PMID- 26892645 TI - Outcomes for Management of Lichen Sclerosus Urethral Strictures by 3 Different Techniques. AB - OBJECTIVE: To evaluate the intermediate-term outcomes from a large, single institution series of patients with lichen sclerosus (LS) who underwent surgical management of their urethral strictures. MATERIALS AND METHODS: We retrospectively reviewed 79 patients who underwent surgical management of their LS urethral strictures from 2003 to 2014, comparing outcomes of patients undergoing a single-stage buccal mucosa graft (BMG) urethroplasty, 2-stage BMG urethroplasty, or perineal urethrostomy (PU). Demographic and surgical outcomes data were collected for all patients. RESULTS: Of the 79 patients, the mean follow-up was 32.4 months, mean age was 50.1 years, and the mean body mass index was 35.7, with morbid obesity (body mass index > 35) in 48% of the cohort. The mean stricture length was 9.6 cm (1.5-21 cm), with 62% of patients having a bulbopendulous stricture. Of the 37 patients who were planned for a 2-stage BMG urethroplasty, 9 (24%) patients had stricture recurrence or recurrent LS in the first-stage BMG. Single-stage BMG urethroplasty was performed in 20 patients with a mean stricture length of 9.47 cm (4-21 cm) and a success rate of 75%. Fourteen patients from the cohort received a PU as the primary treatment, with a success rate of 93%. CONCLUSION: Management of LS strictures continues to pose challenges to the reconstructive surgeon due to the high rate of stricture recurrence and often progression. Patients undergoing single-stage or 2-stage reconstruction often require revision and must be carefully observed for recurrent urethral stricture. PU offers the highest degree of success and should be considered for all patients. PMID- 26892646 TI - Pioglitazone: No Longer a Worry for Bladder Cancer? PMID- 26892644 TI - Association Between Microglia, Inflammatory Factors, and Complement with Loss of Hippocampal Mossy Fiber Synapses Induced by Trimethyltin. AB - Complement-associated factors are implicated in pathogen presentation, neurodegeneration, and microglia resolution of tissue injury. To characterize complement activation with microglial clearance of degenerating mossy fiber boutons, hippocampal dentate granule neurons were ablated in CD-1 mice with trimethyltin (TMT; 2.2 mg/kg, i.p.). Neuronal apoptosis was accompanied by amoeboid microglia and elevations in tumor necrosis factor [Tnfa], interleukin 1beta [Il1b], and Il6 mRNA and C1q protein. Inos mRNA levels were unaltered. Silver degeneration and synaptophysin staining indicated loss of synaptic innervation to CA3 pyramidal neurons. Reactive microglia with thickened bushy morphology showed co-localization of synaptophysin+ fragments. The initial response at 2 days post-TMT included transient elevations in Tnfa, Il1b, Il6, and Inos mRNA levels. A concurrent increase at 2 days was observed in arginase-1 [Arg1], Il10, transforming growth factor beta1 [Tgfb1], and chitinase 3 like-3 [Ym1] mRNA levels. At 2 days, C1q protein was evident in the CA3 with elevated C1qa, C1qb, C3, Cr3a, and Cr3b mRNA levels. mRNA levels remained elevated at 5 days, returning to control by 14 days, corresponding to silver degeneration. mRNA levels for pentraxin3 (Ptx3) were elevated on day 2 and Ptx1 was not altered. Our data suggest an association between microglia reactivity, the induction of anti inflammatory genes concurrent with pro-inflammatory genes and the expression of complement-associated factors with the degeneration of synapses following apoptotic neuronal loss. PMID- 26892647 TI - Renal Tubular Dysfunction in Pediatric Urolithiasis: Proteomic Evidence. AB - OBJECTIVE: To investigate whether inflammation, oxidation, and tubular injury are present in children with stones (RS) compared with healthy controls (HC) by measuring urinary proteins involved in these processes. METHODS: Quantitative proteomic comparison of pooled urine from RS (N = 30, 24 females, mean age 12.95 +/- 4.03 years) versus age- and gender-matched HC (N = 30), using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest were selected using the following criteria: (1) >=5 spectral counts; (2) >=2-fold difference in spectral counts; and (3) P-value <=.05 for Fisher's exact test. RESULTS: Of the 1813 proteins identified, 230 met the above criteria, with 163 proteins upregulated in the RS group and 67 upregulated in HC. Functional analysis revealed 19 inflammatory proteins, 5 proteins involved in oxidative stress, and 5 involved in tubular injury. Of those proteins, NADPH-oxidase, a major source of reactive oxygen species, was only found in the RS group, whereas glutathione S-transferase A2, an important antioxidant enzyme, was more abundant in controls. ELISA analysis confirmed statistically significant differences in the urinary excretion of retinol-binding protein 4, a marker of proximal tubular dysfunction, between stone patients with hypercalciuria and controls. CONCLUSION: We provide proteomic evidence of oxidative stress, inflammation, and tubular injury in children with renal stones. We speculate that inflammation and changes in the oxidant antioxidant balance may cause tubular damage in these patients. Targeting these proteins may have therapeutic benefits. PMID- 26892648 TI - On the Chemistry and Physical Properties of Flux and Floating Zone Grown SmB6 Single Crystals. AB - Recent theoretical and experimental findings suggest the long-known but not well understood low temperature resistance plateau of SmB6 may originate from protected surface states arising from a topologically non-trivial bulk band structure having strong Kondo hybridization. Yet others have ascribed this feature to impurities, vacancies, and surface reconstructions. Given the typical methods used to prepare SmB6 single crystals, flux and floating-zone procedures, such ascriptions should not be taken lightly. We demonstrate how compositional variations and/or observable amounts of impurities in SmB6 crystals grown using both procedures affect the physical properties. From X-ray diffraction, neutron diffraction, and X-ray computed tomography experiments we observe that natural isotope containing (SmB6) and doubly isotope enriched ((154)Sm(11)B6) crystals prepared using aluminum flux contain co-crystallized, epitaxial aluminum. Further, a large, nearly stoichiometric crystal of SmB6 was successfully grown using the float-zone technique; upon continuing the zone melting, samarium vacancies were introduced. These samarium vacancies drastically alter the resistance and plateauing magnitude of the low temperature resistance compared to stoichiometric SmB6. These results highlight that impurities and compositional variations, even at low concentrations, must be considered when collecting/analyzing physical property data of SmB6. Finally, a more accurate samarium-154 coherent neutron scattering length, 8.9(1) fm, is reported. PMID- 26892649 TI - Determination of key diffusion and partition parameters and their use in migration modelling of benzophenone from low-density polyethylene (LDPE) into different foodstuffs. AB - The mass transport process (migration) of a model substance, benzophenone (BZP), from LDPE into selected foodstuffs at three temperatures was studied. A mathematical model based on Fick's Second Law of Diffusion was used to simulate the migration process and a good correlation between experimental and predicted values was found. The acquired results contribute to a better understanding of this phenomenon and the parameters so-derived were incorporated into the migration module of the recently launched FACET tool (Flavourings, Additives and Food Contact Materials Exposure Tool). The migration tests were carried out at different time-temperature conditions, and BZP was extracted from LDPE and analysed by HPLC-DAD. With all data, the parameters for migration modelling (diffusion and partition coefficients) were calculated. Results showed that the diffusion coefficients (within both the polymer and the foodstuff) are greatly affected by the temperature and food's physical state, whereas the partition coefficient was affected significantly only by food characteristics, particularly fat content. PMID- 26892650 TI - Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome. AB - Malignant melanoma is considered the most lethal skin cancer if it is not detected and treated during its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (ie, unilateral lineage, multigenerational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. These patients have a high risk of developing multiple primary melanomas and internal organ malignancies, especially pancreatic cancer; therefore, a multidisciplinary approach is necessary in many cases. The value of dermoscopic examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. This must be performed with care, however, and only by qualified individuals trained in cancer risk analysis. PMID- 26892652 TI - Familial skin cancer syndromes: Increased melanoma risk. AB - Phenotypic traits, such as red hair and freckling, increase melanoma risk by 2- to 3-fold. In addition, approximately 10% of melanomas are caused by inherited germline mutations that increase melanoma risk from 4- to >1000-fold. This review highlights the key genes responsible for inherited melanoma, with an emphasis on when a patient should undergo genetic testing. Many genetic syndromes associated with increased melanoma risk are also associated with an increased risk of other cancers. Identification of these high-risk patients is essential for preventive behavior reinforcement, genetic counseling, and ensuring other required cancer screenings. PMID- 26892651 TI - Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling. AB - Recent advances in cancer genomics have enabled the discovery of many cancer predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of (and be able to recognize) the clinical signs in high-risk patients in different contexts. Personal and family histories of cancer should always be sought in patients with multiple nevi or a positive history for melanoma, and should be updated annually. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors in cases of BAP1 melanoma syndrome, should also be recognized early. These patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if a risk for internal malignancy is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages; a multidisciplinary approach to their cancer screening and treatment is ideal. PMID- 26892654 TI - Why do port-wine stains (PWS) on the lateral face respond better to pulsed dye laser (PDL) than those located on the central face? AB - BACKGROUND: After pulsed dye laser (PDL) treatment, facial lateral port-wine stains (PWS) clear quicker and more completely than central PWS do. OBJECTIVE: We sought to investigate whether the difference in the efficacy of the treatment between central and lateral facial PWS was related to different histologic manifestations. METHOD: Thirteen patients with PWS had biopsies and underwent PDL treatments in both central and lateral areas of the face. The hypothesis was tested by correlating the PWS response to PDL with the depth and diameter of the PWS vessels. The clinical efficacy was assessed by chromameter 2 months after the final PDL treatment, whereas diameter and depth of PWS vessels were measured in biopsy specimens. RESULTS: All patients were treated on central and lateral facial sites. The chromameter evaluation showed that the average blanching rate was 34.01% and 8.68% for lateral and central facial sites, respectively (P < .05), which suggests a better response to PDL treatment in the lateral than in the central area. Histologic manifestations showed that vessels in the lateral regions were primarily located in the papillary dermis, whereas in the central regions they were extensively distributed from the dermis into the subcutaneous tissue. LIMITATIONS: The small number of cases included in this study and the lack of follow-up longer than 2 months constitute limitations. CONCLUSION: Lateral facial PWS respond better to PDL than PWS located in the central face. Differences in vessel location and diameter may be responsible for the variations in PWS response to PDL. PMID- 26892655 TI - Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. AB - Muir-Torre syndrome (MTS) is a rare genetic condition that predisposes individuals to skin tumors and visceral malignancies. Because of the potentially aggressive nature of internal malignancies and sebaceous carcinoma, and the tendency to have multiple low-grade visceral cancers, close cancer surveillance is required in individuals and their families with this usually autosomal dominant disorder. Although the majority of MTS is caused by mutations in DNA mismatch repair genes resulting in microsatellite instability, a newly described subtype of MTS does not demonstrate microsatellite instability and may be inherited in an autosomal recessive pattern. In addition, MTS may be unmasked in transplant recipients taking specific immunosuppressant drugs or other immunosuppressed patients. Neoplasms may be subject to immunohistochemistry or both immunohistochemistry and genetic testing to confirm the diagnosis of MTS. Here, we offer an update and an approach to the diagnosis and management of MTS with a particular emphasis on the role of immunohistochemistry and genetic testing. PMID- 26892653 TI - Familial skin cancer syndromes: Increased risk of nonmelanotic skin cancers and extracutaneous tumors. AB - Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease. PMID- 26892656 TI - Experience with topical timolol maleate for the treatment of ulcerated infantile hemangiomas (IH). PMID- 26892657 TI - Lack of TERT promoter mutations in melanomas with extensive regression. PMID- 26892658 TI - High specificity and sensitivity of NRAS Q61R immunohistochemistry (IHC) in melanomas. PMID- 26892660 TI - Persistence and failure rates of adalimumab monotherapy in biologic-naive patients with psoriasis: A retrospective study. PMID- 26892659 TI - Omalizumab in patients with severe and refractory solar urticaria: A phase II multicentric study. PMID- 26892661 TI - Characteristics and treatment of adult-onset linear morphea: A retrospective cohort study of 61 patients at 3 tertiary care centers. PMID- 26892662 TI - The alcoholic bus driver and the dermatology consultation: Legal, moral, and ethical considerations. PMID- 26892665 TI - Dermoscopy of poikilodermatous mycosis fungoides (MF). PMID- 26892666 TI - A simple and effective treatment for nasal telangiectasia: Needle-assisted electrocoagulation. PMID- 26892668 TI - Visualizing fewer parathyroid glands may be associated with lower hypoparathyroidism following total thyroidectomy. AB - BACKGROUND: It remains uncertain whether the number of parathyroid glands (PGs) seen during extra-capsular dissection impacts short- and long-term hypoparathyroidism. Our study aimed to address this by analyzing patients who underwent total thyroidectomy for benign disease. METHODS: Consecutive patients undergoing total thyroidectomy were analyzed. The extra-capsular dissection technique was performed throughout the study period. The number of PGs identified, auto-transplanted and found on excised specimen was recorded prospectively. The number of PGs in situ was equaled to four minus the number of PGs auto-transplanted and PGs found on specimen. Temporary hypoparathyroidism was defined as serum adjusted calcium <2.00 mol/L 24 h after surgery and/or need for oral supplements while protracted hypoparathyroidism meant subnormal PTH (<1.2 pmol/L) at 4-6 weeks and/or need for >6-week oral supplements. Permanent hypoparathyroidism was defined as need for oral supplements for >=1 year. RESULTS: Five-hundred and sixty-nine patients were eligible for analysis. After adjusting for other significant parameters, greater number of PGs identified was an independent risk factor for temporary (p < 0.001) and protracted hypoparathyroidism (p = 0.007). Mean recovery time from protracted hypoparathyroidism for identifying <=three PGs was significantly shorter than identifying all four PGs (2.8 vs. 7.8 months, p < 0.001). Chance of having all four PGs in situ decreased with greater number of PGs identified (p < 0.001). CONCLUSIONS: When the extra-capsular technique was adopted during total thyroidectomy, identifying fewer PGs in their orthotopic positions not only lowered risk of temporary and protracted hypoparathyroidism but also shortened recovery from protracted hypoparathyroidism. PMID- 26892667 TI - Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). AB - BACKGROUND: PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. METHODS: Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0-4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. RESULTS: 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55-0.90); tablet vs paper: 0.81 (0.62-0.96); IVRS vs paper: 0.78 (0.60-0.91); 89 % of ICCs were >=0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = -0.04 [-0.16-0.22]; tablet vs paper = -0.02 [-0.11-0.14]; IVRS vs paper = 0.02 [-0.07-0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/-0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported "no problems" responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. CONCLUSIONS: Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. TRIAL REGISTRATION: NCT Clinicaltrials.gov identifier: NCT02158637. PMID- 26892669 TI - Measurement of pulse wave velocity in normal ageing: comparison of Vicorder and magnetic resonance phase contrast imaging. AB - BACKGROUND: Pulse wave velocity is an important measure of cardiovascular risk, and can be measured by several different techniques. We compared age-related changes in pulse wave velocity derived from carotid and femoral artery waveforms using the Vicorder device and descending thoracic aorta time velocity curves using phase contrast magnetic resonance imaging (MRI) in a group of normal healthy volunteers, without cardiovascular disease, aged between 20 and 79 years. METHODS: Eighty subjects underwent same-day measurements of Vicorder and MRI pulse wave velocity measurements. RESULTS: Both Vicorder and MRI-based pulse wave velocity measurements were significantly increased with age (R = 0.59 and 0.57 respectively, both P < 0.0001). Vicorder and MRI pulse wave velocities were also significantly related to each other (R = 0.27, P < 0.05), and Bland Altman plots showed that on average Vicorder measurements were 1.6 m/s greater than MRI. In 5% of cases, agreement between the values of the two techniques were above and below 2 standard deviations, and these were at higher levels of pulse wave velocities. Multiple linear stepwise regression analysis confirmed highly significant relationships of both techniques to age (both P < 0.0001), and MRI was also significantly related to heart rate (P = 0.006) but Vicorder was not. CONCLUSIONS: Both Vicorder and MRI perform similarly in detecting age-related changes in pulse wave velocity. Thus, the choice of using one or the other will depend on other aspects of the investigation, such as the need for portability favouring Vicorder, or need for additional cardiovascular imaging favouring MRI. TRIAL REGISTRATION: ClinicalTrials.Gov identifier NCT01504828. PMID- 26892670 TI - A versatile strategy for rapid conditional genome engineering using loxP sites in a small synthetic intron in Plasmodium falciparum. AB - Conditional genome engineering in the human malaria pathogen Plasmodium falciparum remains highly challenging. Here we describe a strategy for facile and rapid functional analysis of genes using an approach based on the Cre/lox system and tailored for organisms with short and few introns. Our method allows the conditional, site-specific removal of genomic sequences of essential and non essential genes by placing loxP sites into a short synthetic intron to produce a module (loxPint) can be placed anywhere in open reading frames without compromising protein expression. When duplicated, the loxPint module serves as an intragenic recombineering point that can be used for the fusion of gene elements to reporters or the conditional introduction of point mutations. We demonstrate the robustness and versatility of the system by targeting the P. falciparum merozoite surface protein 1 gene (msp1), which has previously proven refractory to genetic interrogation, and the parasite exported kinase FIKK10.1. PMID- 26892672 TI - Highly efficient plasmonic tip design for plasmon nanofocusing in near-field optical microscopy. AB - Near-field scanning optical microscopy (NSOM) combined with plasmon nanofocusing is a powerful nano-analytical tool due to its attractive feature of efficient background suppression as well as light energy compression to the nanoscale. In plasmon nanofocusing-based NSOM, the metallic tip plays an important role in inducing plasmon nanofocusing. It is, however, very challenging to control plasmonic properties of tips for plasmon nanofocusing with existing tip fabrication methods, even though the plasmonic properties need to be adjusted to experimental environments such as the sample or excitation wavelength. In this study, we propose an efficient tip design and fabrication which enable one to actively control plasmonic properties for efficient plasmon nanofocusing. Because our method offers flexibility in the material and structure of tips, one can easily modify the plasmonic properties depending on the requirements. Importantly, through optimization of the plasmonic properties, we achieve almost 100% reproducibility in plasmon nanofocusing in our experiments. This new approach of tip fabrication makes plasmon nanofocusing-based NSOM practical and reliable, and opens doors for many scientists working in related fields. PMID- 26892673 TI - Reconstructive Rhinoplasty Using Multiplanar Carved Costal Cartilage. AB - IMPORTANCE: Reconstructive rhinoplasty often requires the use of cartilage grafts. Full-thickness autologous costal cartilage grafts provide a large amount of cartilage in a single uncarved block and are often used for major reconstructions. Warping is frequently described as a complication of rib cartilage use in rhinoplasty. OBJECTIVE: To describe an approach to cartilage carving whereby a single block of cartilage is carved in a multiplanar manner to mimic or redefine the anatomic relationships and resist warping. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of reconstructive rhinoplasty cases using multiplanar costal cartilage grafting technique was performed. A consecutive sample of 11 patients with complex nasal deformity underwent reconstruction with an autologous costal cartilage block carved in 3 dimensions to address complex deformities at the University of New Mexico Hospital between January 2010 and December 2014. The follow-up period ranged from 3 to 36 months. INTERVENTIONS: Autologous rib cartilage harvest was performed to obtain a full thickness segment of rib cartilage. The deficient or malformed nasal cartilage is defined and soft tissue prepared using an open rhinoplasty approach. Rib cartilage graft curvature is removed to create a uniform, symmetric, solid block of cartilage. A cartilage graft is carved in a multiplanar fashion to simulate normal nasal anatomy. MAIN OUTCOMES AND MEASURES: Postoperative evaluation of nasal airway function, cartilage graft warping, and aesthetic outcomes were reported in the follow-up period. Nasal Obstructive Symptom Evaluation (NOSE) scores are documented in the majority of cases and were obtained at least 3 months postoperatively. RESULTS: Overall, 11 patients with complex nasal deformity underwent reconstruction with an autologous costal cartilage block carved in 3 dimensions. The most common use was for reconstruction of the septum with the upper lateral cartilage. There were no major complications. No patients experienced graft warping in the follow-up period. Several patients required minor revision procedures. All patients reported improved nasal airway and improved aesthetic appearance of the nose. CONCLUSIONS AND RELEVANCE: Multiplanar costal cartilage grafting is a useful surgical technique for complex reconstructive rhinoplasty that yields optimal and predictable results. LEVEL OF EVIDENCE: 4. PMID- 26892671 TI - The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced obesity in rats. AB - BACKGROUND AND PURPOSE: Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain-related mechanism. Here, we investigated the role of the brain renin-angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan. METHODS: Transgenic rats with a brain-specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild-type, Sprague Dawley (SD) rats were fed (3 months) with a high calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg.kg(-1) .d(-1) , 3 months). RESULTS: Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain-dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro-opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats. CONCLUSIONS: The brain renin-angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II levels are low in brain, rats are protected from developing diet-induced obesity and obesity-related metabolic impairments. We further suggest that telmisartan at least partly lowers body weight via a CNS-driven mechanism. PMID- 26892674 TI - Damage-tolerance strategies for nacre tablets. AB - Nacre, a natural armor, exhibits prominent penetration resistance against predatory attacks. Unraveling its hierarchical toughening mechanisms and damage tolerance design strategies may provide significant inspiration for the pursuit of high-performance artificial armors. In this work, relationships between the structure and mechanical performance of nacre were investigated. The results show that other than their brick-and-mortar structure, individual nacre tablets significantly contribute to the damage localization of nacre. Affected by intracrystalline organics, the tablets exhibit a unique fracture behavior. The synergistic action of the nanoscale deformation mechanisms increases the energy dissipation efficiency of the tablets and contributes to the preservation of the structural and functional integrity of the shell. PMID- 26892675 TI - Decompressive craniectomy 116 h after malignant middle cerebral artery infarction. AB - The optimal timing of decompressive craniectomy in pediatric patients after presentation with malignant middle cerebral artery infarction is unknown. We report herein the case of a previously healthy 6-year-old Japanese girl who had good outcome after emergency decompressive craniectomy 116 h after malignant middle cerebral artery infarction. This case suggests that the timing of decompressive craniectomy can be delayed until deterioration of neurological findings and, compared with adults, a more prolonged time course for surgical intervention might be acceptable. PMID- 26892676 TI - Surface Molecularly Imprinted Polymer of Chitosan Grafted Poly(methyl methacrylate) for 5-Fluorouracil and Controlled Release. AB - The molecular surface imprinted graft copolymer of chitosan with methyl methacrylate (MIP-CS-g-PMMA) were prepared by free radical polymerization with 5 fluorouracil (5-FU) as the template molecule using initiator of ammonium persulfate as adsorption system. MIPs were characterized by FTIR, X-ray diffraction, thermo-gravimetric analysis, (1)H NMR and SEM. The mechanism of graft copolymerization and factors affected graft reaction were studied in details, and the optimum reaction conditions (to the highest %G and %E as the standard) were obtained at [MMA] 1.2 mol/L, [Chitosan] 16.67 mol/L, [initiator] 0.0062 mol/L, temperature 60 degrees C and reaction time 7 h. MIPs exhibited high recognition selectivity and excellent combining affinity to template molecular. The in vitro release of the 5-FU was highly pH-dependent and time delayed. The release behavior showed that the drugs did not release in simulated gastric fluid (pH = 1.0), and the drug release was small in the simulated small intestinal fluid (pH = 6.8), and drug abrupt release will be produced in the simulated colon fluid (pH = 7.4), indicating excellent colon-specific drug delivery behavior. PMID- 26892678 TI - A case of recurrent hyperreactio luteinalis in three spontaneous pregnancies. AB - Hyperreactio luteinalis is a rare condition in pregnancy characterized by enlarged ovaries with multiple theca luteal cysts, and recurrence of disease has seldom been documented in the literature. This is a case report of a woman who developed recurrent hyperreactio luteinalis with three spontaneous pregnancies. Endocrine evaluation was performed and revealed hyperandrogenism. Ultrasonography was used to assess the ovaries throughout each pregnancy. The ovarian cysts required drainage in the first pregnancy due to severe distention and shortness of breath. Cyst resolution occurred in the post-partum period following each pregnancy. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:502-505, 2016. PMID- 26892679 TI - ASHP Guidelines on Pharmacist Involvement in HIV Care. PMID- 26892677 TI - Factors predicting health services use among older people in China: An analysis of the China Health and Retirement Longitudinal Study 2013. AB - BACKGROUND: Rapid population ageing in China is increasing the numbers of older people who are likely to require health services in response to higher levels of poor perceived health and chronic diseases. Understanding factors influencing health services use at late life will help to plan for increasing needs for health care, reducing inequalities in health services use and releasing severe pressures on a highly variable health care system that has constrained public resources and increasing reliance on health insurance and user payments. METHODS: Drawing on the nationally representative China Health and Retirement Longitudinal Study 2013 data, we apply the Andersen healthcare utilization conceptual model to binary logistic regression multivariate analyses to examine the joint predictors of physical examinations, outpatient and inpatient care among the middle-aged and elderly in China. RESULTS: The multivariate analyses find that both physical examinations and inpatient care rates increase significantly by age when health deteriorates. Females are less likely to use inpatient care. Significant socio economic variations exist in healthcare utilization. Older people with higher education, communist party membership, urban residence, non-agricultural household registration, better financial situation are more likely to have physical examinations or inpatient care. Factors influencing all three types of health care utilization are household expenditure, losing a partner, having multiple chronic diseases or perceiving poor health. With activities of daily living limitations or pain increases the probability of seeing a doctor while with functional loss increases the rates of having physical examinations, but being the ethnic minorities, no social health insurance, with depression, fair or poor memory could be a barrier to having physical examinations or seeing a doctor, which might delay the early diagnose of severe health problems among these groups. Not drinking, not smoking and regular physical exercises are adaptations after having health problems. CONCLUSIONS: As a rapidly ageing society, in order to address the increasing needs and inequalities in health care utilization, China is facing a massive challenge to reform the current health care system, improve equitable access to health insurance and financial affordability for the most disadvantaged, as well as to provide more health education and information to the general public. PMID- 26892681 TI - Spin-orbit coupling enhanced superconductivity in Bi-rich compounds ABi3 (A = Sr and Ba). AB - Recently, Bi-based compounds have attracted attentions because of the strong spin orbit coupling (SOC). In this work, we figured out the role of SOC in ABi3 (A = Sr and Ba) by theoretical investigation of the band structures, phonon properties, and electron-phonon coupling. Without SOC, strong Fermi surface nesting leads to phonon instabilities in ABi3. SOC suppresses the nesting and stabilizes the structure. Moreover, without SOC the calculation largely underestimates the superconducting transition temperatures (Tc), while with SOC the calculated Tc are very close to those determined by measurements on single crystal samples. The SOC enhanced superconductivity in ABi3 is due to not only the SOC induced phonon softening, but also the SOC related increase of electron phonon coupling matrix elements. ABi3 can be potential platforms to construct heterostructure of superconductor/topological insulator to realize topological superconductivity. PMID- 26892680 TI - Hypoxia-inducible factor-2alpha induces expression of type X collagen and matrix metalloproteinases 13 in osteoarthritic meniscal cells. AB - OBJECTIVES: To evaluate whether Hypoxia-inducible factor-2alpha (HIF-2alpha) regulates expression of endochondral ossification-related molecules in human OA meniscus. METHODS: Expressions of HIF-2alpha, type X collagen (COL10), matrix metalloproteinase (MMP)-13, and vascular endothelial growth factor (VEGF) in non OA and OA menisci were analyzed by real-time RT-PCR and immunohistochemistry (IHC). Meniscal cells from OA patients were treated with interleukin-1beta (IL 1beta) and gene expression was analyzed. After knockdown of HIF-2alpha in OA meniscal cells, COL10 and MMP-13 expression were analyzed by RT-PCR, western blotting, immunofluorescence and ELISA. RESULT: Histological analysis demonstrated weak staining of the superficial layer and large round cells in OA meniscus. RT-PCR analysis showed that HIF-2alpha, COL10, MMP-13, and VEGF mRNA expressions were higher in OA than non-OA meniscal cells. IHC showed a coordinated staining pattern of HIF-2alpha, COL10, and MMP-13 in OA meniscus. IL 1beta treatment increased HIF-2alpha, COL10, and MMP-13 expressions in OA meniscal cells, and knockdown of HIF-2alpha suppressed IL-1beta-mediated increase in COL10 and MMP-13 expression. CONCLUSIONS: These results suggested that HIF 2alpha may cause meniscal matrix degradation by transactivation of MMP-13. HIF 2alpha may be a therapeutic target for modulating matrix degradation in both articular cartilage and meniscus during knee OA progression. PMID- 26892683 TI - Expression of DNA methyltransferases 1 and 3B correlates with EZH2 and this 3 marker epigenetic signature predicts outcome in glioblastomas. AB - This study aims to analyze expression of EZH2 and DNA-methyltransferases (DNMT1, 3A and 3B) in astrocytic tumors and investigate their link as well as their correlation with survival, especially in GBMs. Expression of EZH2 and DNMTs (DNMT1, DNMT3A and DNMT3B) in different grades of astrocytomas (n=93) was assessed by qRT-PCR and immunohistochemistry. GBM-U87MG cell line was used for functional studies. Strong immunopositivity (LI>=25%) for EZH2, DNMT1 and DNMT3B was detected in 52%, 56% and 64% cases of GBMs respectively, which was significantly higher as compared to Grade II/III cases. Similarly, their median fold change of mRNA expression was also significantly higher in GBMs. There was also a significant positive correlation between DNMT1/DNMT3B and EZH2 mRNA and protein expression, which was in concordance with TCGA data set. Inhibition of DNMTs in cell line by Azacytidine resulted in down-regulation of EZH2, while knock-down of EZH2 by siRNA was not associated with any significant alteration of DNMTs, indicating that EZH2 expression in GBMs is possibly regulated by DNMTs, but not the reverse. Strong immunopositivity for EZH2, DNMT1 and DNMT3B were individually associated with significantly shorter survival and showed no correlation with IDH1 mutation status. In addition, the combination of these 3 markers represented an independent prognostic signature with cases having weak/negative expression of all 3 markers being associated with best prognosis. For the first time, the present study describes an epigenetic prognostic signature in GBMs based on immunohistochemical expression of EZH2, DNMT1 and 3B which can be used easily in routine neuropathology practice. PMID- 26892684 TI - Genome-wide data reveal cryptic diversity and genetic introgression in an Oriental cynopterine fruit bat radiation. AB - BACKGROUND: The Oriental fruit bat genus Cynopterus, with several geographically overlapping species, presents an interesting case study to evaluate the evolutionary significance of coexistence versus isolation. We examined the morphological and genetic variability of congeneric fruit bats Cynopterus sphinx and C. brachyotis using 405 samples from two natural contact zones and 17 allopatric locations in the Indian subcontinent; and investigated the population differentiation patterns, evolutionary history, and the possibility of cryptic diversity in this species pair. RESULTS: Analysis of microsatellites, cytochrome b gene sequences, and restriction digestion based genome-wide data revealed that C. sphinx and C. brachyotis do not hybridize in contact zones. However, cytochrome b gene sequences and genome-wide SNP data helped uncover a cryptic, hitherto unrecognized cynopterine lineage in northeastern India coexisting with C. sphinx. Further analyses of shared variation of SNPs using Patterson's D statistics suggest introgression between this lineage and C. sphinx. Multivariate analyses of morphology using genetically classified grouping confirmed substantial morphological overlap between C. sphinx and C. brachyotis, specifically in the high elevation contact zones in southern India. CONCLUSION: Our results uncover novel diversity and detect a pattern of genetic introgression in a cryptic radiation of bats, demonstrating the complicated nature of lineage diversification in this poorly understood taxonomic group. Our results highlight the importance of genome-wide data to study evolutionary processes of morphologically similar species pairs. Our approach represents a significant step forward in evolutionary research on young radiations of non-model species that may retain the ability of interspecific gene flow. PMID- 26892685 TI - Aromatic Monochlorination Photosensitized by DDQ with Hydrogen Chloride under Visible-Light Irradiation. AB - Photochlorination of aromatic substrates by hydrogen chloride with 2,3-dichloro 5,6-cyano-p-benzoquinone (DDQ) occurs efficiently to produce the corresponding monochlorinated products selectively under visible-light irradiation. The yields for the chlorination of phenol were 70 % and 18 % for p- and o-chlorophenol, respectively, without formation of further chlorinated products. The photoinduced chlorination is initiated by electron transfer from Cl(-) to the triplet excited state of DDQ. The radical intermediates involved in the photochemical reaction have been detected by time-resolved transient absorption measurements. PMID- 26892686 TI - What factors affect patient access and engagement with clubfoot treatment in low- and middle-income countries? Meta-synthesis of existing qualitative studies using a social ecological model. AB - OBJECTIVES: To conduct a systematic synthesis of previous research to identify factors that affect treatment-seeking for clubfoot and community-level interventions to improve engagement in low- and middle-income counties. METHODS: A search of five databases was conducted, and articles screened using six criteria. Quality was appraised using the Critical Appraisal Skills Programme checklist. Eleven studies were identified for inclusion. Analysis was informed by a social ecological model, which specifies five inter-related factors that may affect treatment-seeking: intrapersonal, interpersonal, institutional, community or socio-cultural factors and public policy. RESULTS: Intrapersonal barriers experienced were a lack of income and additional responsibilities. At the interpersonal level, support from fathers, the extended family and wider community affected on treatment-seeking. Institutional or organisational factors included long distances to treatment centres, insufficient information about treatments and challenges following treatment. Guardians' beliefs about the causes of clubfoot shaped behaviour. At the level of public policy, two-tiered healthcare systems made it difficult for some groups to access timely care. Interventions to address these challenges included counselling sessions, outreach clinics, brace recycling and a range of education programmes. CONCLUSIONS: This study identifies factors that affect access and engagement with clubfoot treatment across diverse settings and strategies to address them. PMID- 26892687 TI - Embracing Ritual Healing: The Case of Sazuke in Tenrikyo in Contemporary Taiwan. AB - This paper will explore how the practice of ritual healing (sazuke) has played a prominent part in the propagation of a Japanese new religious movement (Tenrikyo) in Taiwan. The author firstly unravels the mystery of Tenrikyo's healing ritual (sazuke) and its role in enabling Taiwanese followers' potential to re-establish their relationship with the world. The author points out that sazuke is similar to Taiwanese folk therapy and fits into Taiwan's multi-medical systems. The author also examines the features of Tenrikyo's healing practice in Taiwan and discusses the evolution of sazuke from a non-institutionalised practice to a bureaucratised one. The author then advances to a more widely theoretical consideration by discussing how sazuke became a force that enabled Taiwanese people to respond to the changing world and how it facilitated peoples' transformation when they were confronted by daily troubles and difficulties. PMID- 26892682 TI - An 8-gene mRNA expression profile in circulating tumor cells predicts response to aromatase inhibitors in metastatic breast cancer patients. AB - BACKGROUND: Molecular characterization of circulating tumor cells (CTC) is promising for personalized medicine. We aimed to identify a CTC gene expression profile predicting outcome to first-line aromatase inhibitors in metastatic breast cancer (MBC) patients. METHODS: CTCs were isolated from 78 MBC patients before treatment start. mRNA expression levels of 96 genes were measured by quantitative reverse transcriptase polymerase chain reaction. After applying predefined exclusion criteria based on lack of sufficient RNA quality and/or quantity, the data from 45 patients were used to construct a gene expression profile to predict poor responding patients, defined as disease progression or death <9 months, by a leave-one-out cross validation. RESULTS: Of the 45 patients, 19 were clinically classified as poor responders. To identify them, the 75% most variable genes were used to select genes differentially expressed between good and poor responders. An 8-gene CTC predictor was significantly associated with outcome (Hazard Ratio [HR] 4.40, 95% Confidence Interval [CI]: 2.17-8.92, P < 0.001). This predictor identified poor responding patients with a sensitivity of 63% and a positive predictive value of 75%, while good responding patients were correctly predicted in 85% of the cases. In multivariate Cox regression analysis, including CTC count at baseline, the 8-gene CTC predictor was the only factor independently associated with outcome (HR 4.59 [95% CI: 2.11 9.56], P < 0.001). This 8-gene signature was not associated with outcome in a group of 71 MBC patients treated with systemic treatments other than AI. CONCLUSIONS: An 8-gene CTC predictor was identified which discriminates good and poor outcome to first-line aromatase inhibitors in MBC patients. Although results need to be validated, this study underscores the potential of molecular characterization of CTCs. PMID- 26892689 TI - Dynamical Network of HIV-1 Protease Mutants Reveals the Mechanism of Drug Resistance and Unhindered Activity. AB - HIV-1 protease variants resist drugs by active and non-active-site mutations. The active-site mutations, which are the primary or first set of mutations, hamper the stability of the enzyme and resist the drugs minimally. As a result, secondary mutations that not only increase protein stability for unhindered catalytic activity but also resist drugs very effectively arise. While the mechanism of drug resistance of the active-site mutations is through modulating the active-site pocket volume, the mechanism of drug resistance of the non-active site mutations is unclear. Moreover, how these allosteric mutations, which are 8 21 A distant, communicate to the active site for drug efflux is completely unexplored. Results from molecular dynamics simulations suggest that the primary mechanism of drug resistance of the secondary mutations involves opening of the flexible protease flaps. Results from both residue- and community-based network analyses reveal that this precise action of protease is accomplished by the presence of robust communication paths between the mutational sites and the functionally relevant regions: active site and flaps. While the communication is more direct in the wild type, it traverses across multiple intermediate residues in mutants, leading to weak signaling and unregulated motions of flaps. The global integrity of the protease network is, however, maintained through the neighboring residues, which exhibit high degrees of conservation, consistent with clinical data and mutagenesis studies. PMID- 26892690 TI - Interim analysis of a randomized controlled trial comparing laparoscopic radiofrequency volumetric thermal ablation of uterine fibroids with laparoscopic myomectomy. AB - OBJECTIVE: To compare 24-month patient-reported outcomes following laparoscopic radiofrequency volumetric thermal ablation (RFVTA) and laparoscopic myomectomy in patients with uterine fibroids. METHOD: An interim analysis of 24-month follow-up data from a randomized controlled trial was performed at Tubingen University Women's Hospital between November 1, 2012 and May 30, 2015. Premenopausal patients, at least 18years of age, who were menstruating, were randomly assigned to be treated for symptomatic uterine fibroids with either RFVTA or laparoscopic myomectomy. The outcomes included in the present per-protocol analysis were patients' responses to validated questionnaires and long-term safety. RESULTS: The study enrolled 51 patients; 21 and 22 patients in the RFVTA and laparoscopic myomectomy groups, respectively, completed 24months of follow-up. Improvements in the severity of symptoms from baseline were reported by participants in both the RFVTA (P<0.001) and laparoscopic myomectomy groups (P=0.001). A significant improvement in health-related quality of life was observed in the laparoscopic myomectomy group (P=0.040); a non-significant improvement was recorded in the RFVTA group (P=0.083). A trocar-site hematoma occurred in one patient in the laparoscopic myomectomy group. Further surgical interventions were recorded in three patients in the RFVTA group but these were unrelated to fibroid symptoms. CONCLUSIONS: These 24-month data suggest equivalence in safety and patient reported efficacy of RFVTA and laparoscopic myomectomy. ClinicalTrials.gov:NCT01750008. PMID- 26892691 TI - Vaginohysteroscopy for the diagnosis and treatment of vaginal lesions. AB - BACKGROUND: The vaginoscopic approach for hysteroscopy allows detailed endoscopic evaluation of the vaginal walls, fornices, and exocervix. OBJECTIVES: To review the feasibility and efficacy of vaginohysteroscopy in the diagnosis and treatment of vaginal lesions. SEARCH STRATEGY: A systematic review was performed of PubMed/Medline, Embase, Google Scholar, and the Cochrane Database to identify papers published in English. The search terms were "hysteroscopy," "vaginoscopy," "vagino-hysteroscopy," and "vaginal lesion." The last review was performed on January 31, 2015. SELECTION CRITERIA: Studies in which the diagnosis and treatment of vaginal lesions used the vaginoscopic approach and hysteroscopic instrumentation were reviewed. DATA COLLECTION AND ANALYSIS: Data were extracted from the identified studies and then analyzed. MAIN RESULTS: Thirteen studies were reviewed. Eleven described one case; one reported observations from two patients, and one study reported a case series. All vaginohysteroscopies reported were performed successfully and without significant complications. CONCLUSIONS: Vaginohysteroscopy is an easy way to gain access to the cervical canal and an important tool with which to diagnose and treat vaginal lesions. PMID- 26892692 TI - Three-arm age-matched retrospective cohort study of obstetric outcomes of donor oocyte pregnancies. AB - OBJECTIVE: To evaluate and compare obstetric complications between women who conceived after oocyte donation and age-matched control women who conceived spontaneously or by autologous in vitro fertilization (IVF). METHODS: In a retrospective cohort study, data were assessed from all women who conceived after oocyte donation and delivered a live neonate after 24weeks of pregnancy between January 2007 and December 2014 at a UK hospital. Two age-matched control groups one containing women who conceived after autologous IVF and the other containing women who conceived spontaneously-were used for comparison. The primary study outcome was hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia). Multivariate analysis was performed by logistic regression. RESULTS: Each group included 45 women. Hypertensive disorders in pregnancy affected 15 (33%) women in the study group, 3 (7%) women who conceived after autologous IVF, and 3 (7%) who conceived spontaneously. The risk of hypertensive disorders in pregnancy was significantly higher in the donor oocyte group (odds ratio 5.85, 95% confidence interval 1.42-23.9; P=0.01). CONCLUSION: Women who conceived after oocyte donation had an increased risk of hypertensive disorders. Oocyte donation should be managed as an independent risk factor, and couples should be counselled appropriately. PMID- 26892688 TI - Role of ribosomal protein mutations in tumor development (Review). AB - Ribosomes are cellular machines essential for protein synthesis. The biogenesis of ribosomes is a highly complex and energy consuming process that initiates in the nucleolus. Recently, a series of studies applying whole-exome or whole-genome sequencing techniques have led to the discovery of ribosomal protein gene mutations in different cancer types. Mutations in ribosomal protein genes have for example been found in endometrial cancer (RPL22), T-cell acute lymphoblastic leukemia (RPL10, RPL5 and RPL11), chronic lymphocytic leukemia (RPS15), colorectal cancer (RPS20), and glioma (RPL5). Moreover, patients suffering from Diamond-Blackfan anemia, a bone marrow failure syndrome caused by mutant ribosomal proteins are also at higher risk for developing leukemia, or solid tumors. Different experimental models indicate potential mechanisms whereby ribosomal proteins may initiate cancer development. In particular, deregulation of the p53 tumor suppressor network and altered mRNA translation are mechanisms likely to be involved. We envisage that changes in expression and the occurrence of ribosomal protein gene mutations play important roles in cancer development. Ribosome biology constitutes a re-emerging vital area of basic and translational cancer research. PMID- 26892693 TI - A meta-analysis of the worldwide prevalence of pica during pregnancy and the postpartum period. AB - BACKGROUND: Although pica has long been associated with pregnancy, the exact prevalence in this population remains unknown. OBJECTIVES: To estimate the prevalence of pica during pregnancy and the postpartum period, and to explain variations in prevalence estimates by examining potential moderating variables. SEARCH STRATEGY: PsycARTICLES, PsycINFO, PubMed, and Google Scholar were searched from inception to February 2014 using the keywords pica, prevalence, and epidemiology. SELECTION CRITERIA: Articles estimating pica prevalence during pregnancy and/or the postpartum period using a self-report questionnaire or interview were included. DATA COLLECTION AND ANALYSIS: Study characteristics, pica prevalence, and eight potential moderating variables were recorded (parity, anemia, duration of pregnancy, mean maternal age, education, sampling method employed, region, and publication date). Random-effects models were employed. MAIN RESULTS: In total, 70 studies were included, producing an aggregate prevalence estimate of 27.8% (95% confidence interval 22.8-33.3). In light of substantial heterogeneity within the study model, the primary focus was identifying moderator variables. Pica prevalence was higher in Africa compared with elsewhere in the world, increased as the prevalence of anemia increased, and decreased as educational attainment increased. CONCLUSIONS: Geographical region, anemia, and education were found to moderate pica prevalence, partially explaining the heterogeneity in prevalence estimates across the literature. PMID- 26892695 TI - Randomized controlled trial comparing 200MUg and 400MUg sublingual misoprostol for prevention of primary postpartum hemorrhage. AB - OBJECTIVE: To compare efficacy and adverse effects of 200MUg and 400MUg misoprostol for prevention of postpartum hemorrhage (PPH). METHODS: In a randomized control trial, women with term singleton pregnancies in active labor attending University College Hospital, Ibadan, Nigeria, were enrolled between July 2011 and February 2012. Participants were randomly assigned using random numbers (block size four) to receive 200MUg or 400MUg sublingual misoprostol after delivery of the anterior shoulder, alongside intravenous oxytocin. Investigators were masked to group assignment, but participants were not. The primary outcomes were blood loss up to 1h after delivery, PPH (blood loss >=500mL), and adverse effects. RESULTS: Overall, 62 patients were assigned to each group. No significant differences between the 200-MUg and 400-MUg groups were recorded in mean peripartum blood loss (307+/-145mL vs 296+/-151mL; P=0.679) and PPH occurrence (5 [8.1%] vs 6 [9.7%] women; P=0.752). Noticeable adverse effects were reported by 16 (25.8%) women in the 200-MUg group and 42 (67.7%) in the 400-MUg group (P<0.001). Risk of shivering was significantly lower with 200MUg than 400MUg (relative risk 0.33, 95% confidence interval 0.19-0.58). CONCLUSION: Blood loss and PPH occurrence did not differ by misoprostol dose, but a 200-MUg dose was associated with a reduction in adverse effects. Pan Africa Clinical Trials Registry: PACTR201505001107182. PMID- 26892694 TI - A randomized controlled trial of abdominal binders for the management of postoperative pain and distress after cesarean delivery. AB - OBJECTIVE: To determine whether abdominal binders effectively control pain and distress after cesarean delivery. METHODS: A prospective randomized controlled trial was conducted between April and November, 2014, among women undergoing cesarean delivery (low-transverse skin incision) at two US hospitals. Participants were randomly allocated to either the abdominal binder or control groups on entry to the operating suite. Masking was not possible. Patients in the abdominal binder group were fitted with a device before leaving the operating room and were encouraged to wear it constantly, although breaks were allowed. The primary outcomes were postoperative distress (measured by the Symptom Distress Scale [SDS]) and pain (measured by a visual analog scale [VAS]). Individuals who asked to be removed from the study within 6hours of surgery were excluded from analyses. RESULTS: Analyses included 87 patients in the abdominal binder group and 68 in the control group. The abdominal binder and control groups did not differ in postoperative day 1 VAS (3.1+/-2.1 vs 3.4+/-2.3; P=0.33), postoperative day 2 VAS (3.0+/-1.9 vs 3.8+/-2.2; P=0.16), postoperative day 1 SDS (21.5+/-5.4 vs 21.8+/-5.1; P=0.87), and postoperative day 2 SDS (19.4+/-4.8 vs 19.9+/-5.0; P=0.53). CONCLUSION: Postoperative pain and distress scores after cesarean delivery were not affected by abdominal binders. ClinicalTrials.gov:NCT02129894. PMID- 26892696 TI - Reproductive potential of mature oocytes after conventional ovarian hyperstimulation for in vitro fertilization. AB - OBJECTIVE: To compare cumulative live birth rate according to the rate of use of metaphase II (MII) oocytes in conventional ovarian stimulation protocols for in vitro fertilization (IVF) or intracytoplasmic sperm injection. METHODS: In a cohort study, patients aged 18-38 years undergoing their first IVF treatment at one US center were enrolled between February 1, 2009, and August 31, 2013. Ovarian response was categorized by the yield of MII oocytes (low: 1-2; intermediate: 3-6; high: >=7). The main outcome measure was cumulative live birth rate over a 6-month period. RESULTS: Among 250 participants, 3240 oocytes (mean+/ SEM 12.96+/-0.50) were retrieved and there were 152 (60.8%) live births. Overall, 172 (68.8%) participants had a high oocyte yield, 61 (24.4%) an intermediate yield, and 17 (6.8%) a low yield. The cumulative live birth rate was 58.8% (10/17) in the low-yield group, 55.7% (34/61) in the intermediate-yield group, and 62.8% (108/172) in the high-yield group (P=0.35). CONCLUSION: In conventional ovarian stimulation, live birth rate is not affected by the ovarian response. Whether oocytes produced from a low ovarian response are biologically more effective than oocytes obtained from a high ovarian response remains to be determined. PMID- 26892697 TI - Correlation of first-trimester serum levels of pregnancy-associated plasma protein A with small-for-gestational-age neonates and preterm births. AB - OBJECTIVE: To analyze the relationship between first-trimester levels of pregnancy-associated plasma protein A (PAPP-A) and small-for-gestational-age (SGA) neonates and preterm births, and to assess predictive utility for these events. METHODS: A prospective study was conducted among women undergoing first trimester screening between January 1, 2012, and December 31, 2013, at two centers in Pune, India. Serum PAPP-A levels, pregnancy course, and outcome were assessed. RESULTS: Overall, 1474 women were included. An association was found between the lowest quintile of PAPP-A levels (<0.4 multiples of median) for both SGA (<10th centile; 20.9% of cases in this PAPP-A quintile) and preterm birth (<37weeks; 15.8%). Women in the lowest quintile of PAPP-A concentration had a significantly increased risk of SGA (<10th centile) than did those with higher concentrations (adjusted odds ratio 2.92, 95% confidence interval 2.00-4.27). Their risk of preterm birth (<37weeks) was also increased (adjusted odds ratio 1.84, 95% confidence interval 1.25-2.72). The predictive sensitivities of the lowest quintile of PAPP-A were 35.85% for SGA (<10th centile) and 27.92% for preterm birth (<37weeks). CONCLUSION: Low levels of PAPP-A were associated with SGA and preterm births; however, poor predictive sensitivity could restrict clinical utility of this marker when used alone. PMID- 26892698 TI - A never-smoker lung adenocarcinoma patient with a MET exon 14 mutation (D1028N) and a rapid partial response after crizotinib. AB - During the past decade, the treatment of lung adenocarcinomas has been revolutionized with novel molecular targeted therapies. We describe a case of clinical activity of crizotinib in a female patient with a lung adenocarcinoma displaying a MET exon 14 donor splice site mutation (D1028N) detected using next generation sequencing. Within 5 weeks of crizotinib therapy, a partial response was observed in this 67 year-old woman. Further clinical trials of crizotinib are needed for non-small cell lung cancer exhibiting MET mutations. PMID- 26892699 TI - Using the Targeted Solutions Tool(r) to Improve Emergency Department Handoffs in a Community Hospital. AB - BACKGROUND: There is little evidence for solutions to improve the handoff process between units, particularly from the emergency department (ED) to the inpatient unit. A systematic approach was used to improve the handoff communication process between the ED and the four private physician groups serving Juneau, Alaska, that admit and deliver care to patients of a 73-bed, Level 4 trauma center community hospital. METHODS: Data were collected in using the Joint Commission Center for Transforming Healthcare's Targeted Solutions Tool ((r))(TST((r))) to determine the rate of defective handoff communications and the factors that contributed to those defective handoff communications. Targeted solutions were then implemented to specifically address the identified contributing factors. RESULTS: A random sample of 107 handoff opportunities was collected during the baseline phase (November 4, 2011- January 12, 2012) to measure performance and identify the contributing factors that led to defective handoffs. The baseline handoff communications defective rate was 29.9% (32 defective handoffs/107 handoff opportunities). The top four contributing factors, together accounting for 69.8% of all the causes of defective handoffs, were inaccurate/incomplete information, method ineffective, no standardized procedures for an effective handoff, and the person initiating the handoff, known as the "sender," lacks knowledge about the patient. After implementation of targeted solutions to the identified contributing factors, the handoff communications defective rate for the "improve" phase (April 1, 2012-July 29, 2012) was reduced from baseline by 58.2% to 12.5% (13 defective handoffs/104 handoff opportunities), p = 0.002; 2-proportions test. The number of adverse events related to hand-off communications declined as the handoff communications defective rate improved. CONCLUSION: Use of the TST was associated with improvement in the ED handoff communication process. PMID- 26892700 TI - Understanding Patient, Provider, and System Factors Related to Medicaid Readmissions. AB - BACKGROUND: Efforts on reducing hospital readmissions, which are intended to improve quality and reduce costs, tend to focus on elderly Medicare beneficiaries without recognition of another high-risk population--adult nonmaternal Medicaid patients. This study was undertaken to understand the complexity of Medicaid readmission issues at the patient, provider, and system levels. METHODS: Multiple qualitative methods, including site visits to nine safety-net hospitals, patient/family/caregiver inter views, and semistructured interviews with health plans and state Medicaid agencies, were used in 2012 and 2013 to obtain information on patient, provider, and system issues related to Medicaid readmissions; strategies considered or currently used to address those issues; and any perceived financial, regulatory or, other policy factors inhibiting or facilitating readmission reduction efforts. RESULTS: Significant risk factors for Medicaid readmissions included financial stress, high prevalence of mental health and substance abuse disorders, medication nonadherence, and housing instability. Lacking awareness on Medicaid patients' high risk, a sufficient business case, and proven strategies for reducing readmissions were primary barriers for providers. Major hurdles at the system level included shortage of primary care and mental health providers, lack of coordination among providers, lack of partnerships between health plans and providers, and limited data capacity for realtime monitoring of readmissions. CONCLUSIONS: The intertwining of behavioral, socioeconomic, and health factors; the difficulty of accessing appropriate care in the outpatient setting; the lack of clear financial incentives for health care providers to reduce readmissions; and the fragmentation of the current health care system warrant greater attention and more concerted efforts from all stakeholders to reduce Medicaid readmissions. PMID- 26892702 TI - Time for Quality Measures to Get Personal. PMID- 26892701 TI - The Sepsis Early Recognition and Response Initiative (SERRI). PMID- 26892703 TI - The Impact of the Affordable Care Act on Health Care Alliances' Quality Improvement Efforts in Targeted Communities: Perceptions of Health Care Alliance Leaders. PMID- 26892704 TI - Engaging Pediatric Resident Physicians in Quality Improvement Through Resident Led Morbidity and Mortality Conferences. AB - BACKGROUND: Increasingly, medical disciplines have used morbidity and mortality conferences (MMCs) to address quality improvement and patient safety (QI/PS), as well as teach systems-based improvement to graduate trainees. The goal of this educational intervention was to establish a pediatric resident physician-led MMC that not only focused on QI/PS principles but also engaged resident physicians in QI/ PS endeavors in their clinical learning environments. METHODS: Following a needs assessment, pediatric resident physicians at the Stanford University School of Medicine (Stanford, California) established a new MMC model in February 2010 as part of a required QI rotation. Cases were identified, explored, analyzed, and presented by resident physicians using the Johns Hopkins Learning from Defects tool. Discussions during the MMCs were resident physician- directed and systems based, and resulted in projects to address care delivery. Faculty advisors assessed resident physician comprehension of QI/PS. Conferences were evaluated through the end of the 2012-2013 academic year and outcomes tracked through the 2013-2014 academic year to determine trainee involvement in systems change resulting from the MMCs. RESULTS: The MMC was well received and the number of MMCs increased over time. By the end of the 2013-2014 academic year, resident physicians were involved in address ing 14 systems-based issues resulting from 25 MMCs. Examples of the resident physician-initiated improvement work included increasing use of the rapid response team, institution of a gastrostomy (g)-tube order set, and establishing a face-to-face provider handoff for pediatric ICU-to acute-care-floor transfers. CONCLUSION: A resident physician-run MMC exposes resident physicians to QI/PS concepts and principles, enables direct faculty assessment of QI/PS knowledge, and can propel resident physicians into real-time engagement in the culture of safety in a complex hospital environment. PMID- 26892705 TI - Attack in Paris and occupational health. PMID- 26892706 TI - Report from the 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group. AB - The 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held during the annual meeting on 30 October 2015 in Munich. This summit was organized in light of recently published and numerous ongoing CVOTs on diabetes, which have emerged in response to the FDA and the EMA Guidelines. The CVOT Summit stands as a novel conference setup, with the aim of serving as a reference meeting for all topics related to CVOTs in diabetes. Members of the steering committee of the D&CVD EASD Study Group constitute the backbone of the summit. It included presentations of key results on DPP-4 inhibitors, GLP-1-Analogues, SGLT-2 inhibitors, acarbose and insulins. Diabetologists' and cardiologists' perspective on the potential need of new study designs were also highlighted. Furthermore, panel discussions on the design of CVOTs on diabetes were included in the program. The D&CVD EASD Study Group will continue its activity. In-depth discussions and presentations of new CVOTs like LEADER, will be resumed at the 2nd CVOT on diabetes of the D&CVD EASD Study Group, which will be held from 20-22 October 2016 in Munich ( http://www.dcvd.org). PMID- 26892708 TI - The effect of the two feet-in-the-door technique on tobacco deprivation. AB - The 'Foot-in-the-door' (FITD) is a well-known compliance technique that increases compliance with a request. Many investigations on this paradigm have generally used prosocial requests to test the effect of the technique. A new evaluation of the effect of the FITD technique was carried out on tobacco deprivation. A two feet-in-the-door technique in which the target request was preceded by two small target requests was used to encourage students to stop smoking for 24 h. The results were compared with two single foot-in-the- door procedures in which the final request was only preceded by one small request, as well as with a control condition using only a 24 h stop-smoking request. Results showed that the single FITD and the two feet-in-the-door procedures were effective to increase verbal compliance (accepting to stop smoking) but only the two feet-in-the-door technique significantly increased behavioural compliance (not smoking for 24 h) with the request. PMID- 26892709 TI - De novo lipogenesis is suppressed during fasting but upregulated at population decline in cyclic voles. AB - Arvicolines are susceptible to the development of fatty liver during short-term fasting. We examined the potential role of de novo lipogenesis (DNL) (i) in the development of fasting-induced fatty liver and (ii) during a population cycle by measuring the mRNA expression of acetyl-CoA carboxylase-1 (ACC1) and fatty acid synthase (FAS). Laboratory voles (Microtus oeconomus and Microtus arvalis) were fed or fasted for 12 or 18 h and their liver mRNA levels were determined. Both species showed decreased mRNA expression of ACC1 and FAS during fasting. This suggests that DNL does not participate in the development of fatty liver in voles, different from human non-alcoholic fatty liver disease. In wild bank voles (Myodes glareolus), the mRNA levels of the genes of interest were higher during the population decline compared to the increase phase. In conclusion, DNL was suppressed during acute fasting but upregulated during a long-term population decline-a period of purported scarcity of high-quality food. PMID- 26892711 TI - The World Medical Association Launches A Revision of the Declaration of Geneva. PMID- 26892710 TI - Transmurally differentiated measurement of ATP hydrolysis rates in the in vivo porcine hearts. AB - PURPOSE: Compare the transmural distribution of forward creatine kinase reaction (kf,CK ) and ATP hydrolysis rate (kr,ATPase ) in the myocardium of normal porcine heart. Rate constants were extracted from partially relaxed spectra by applying the T1nom method, effectively reducing data acquisition time by up to an order of magnitude. THEORY AND METHODS: T1nom method for double saturation of PCr and Pi is introduced and validated through simulations. Bioenergetics was measured in vivo utilizing one-dimensional chemical shift imaging (1D-CSI) magnetic resonance (31) P spectroscopy. RESULTS: At basal conditions, there was no significant difference between subepicardial layers (EPI) vs. the subendocardial layers (ENDO) for both fluxf,CK and fluxr,ATPase . At high cardiac workload (HWL), where the rate pressure product increased 2.6-fold, PCr/ATP ratio and fluxf,CK showed no significant change in both EPI and ENDO layers, while fluxr,ATPase increased significantly (baseline: 1.11 +/- 0.12 and 1.12 +/- 0.13 MUmol/g/s, EPI and ENDO, respectively; to HWL: 2.35 +/- 0.27 and 2.21 +/- 0.08 MUmol/g/s, EPI and ENDO, respectively, each P < 0.01 vs. baseline). CONCLUSION: In the normal heart, increase of cardiac work state is accompanied by an increase in ATP hydrolysis rate with no changes in CK flux rate. There are no significant differences between EPI vs. ENDO concerning the ATP hydrolysis rate or CK flux rate in both baseline and high cardiac work states. PMID- 26892712 TI - The Ashley Treatment: Improving Quality of Life or Infringing Dignity and Rights? AB - The 'Ashley treatment' (growth attenuation, removal of the womb and breasts buds of a severely disabled child) has raised much ethical controversy. This article starts from the observation that this debate suffers from a lack of careful philosophical analysis which is essential for an ethical assessment. I focus on two central arguments in the debate, namely an argument defending the treatment based on quality of life and an argument against the treatment based on dignity and rights. My analysis raises doubts as to whether these arguments, as they stand in the debate, are philosophically robust. I reconstruct what form good arguments for and against the treatment should take and which assumptions are needed to defend the according positions. Concerning quality of life (Section 2), I argue that to make a discussion about quality of life possible, it needs to be clear which particular conception of the good life is employed. This has not been sufficiently clear in the debate. I fill this lacuna. Regarding rights and dignity (section 3), I show that there is a remarkable absence of references to general philosophical theories of rights and dignity in the debate about the Ashley treatment. Consequently, this argument against the treatment is not sufficiently developed. I clarify how such an argument should proceed. Such a detailed analysis of arguments is necessary to clear up some confusions and ambiguities in the debate and to shed light on the dilemma that caretakers of severely disabled children face. PMID- 26892713 TI - A prospective double-blinded randomized controlled trial comparing systemic stress response in Laparoascopic cholecystectomy between low-pressure and standard-pressure pneumoperitoneum. AB - INTRODUCTION: Laparoscopic cholecystectomy (LC) has become the gold-standard treatment for gallstone diseases. However, despite huge reduction in operative injury, systemic stress response remains high. This randomized controlled trial (RCT) aimed to compare systemic stress response between 2 different techniques of CO2 pneumoperitoneum. METHODS: Trough a prospective, double-blinded RCT, serum levels of cortisol, adrenaline, glucose, and C-reactive protein (CRP) were compared between the two groups consisted of 50 patients undergoing LC under low pressure and standard-pressure CO2 pneimoperitoneum. RESULTS: A total of fifty patients undergoing LC were equally assigned to 2 groups of twenty five patients. Average age was 48 +/- 13.8 years (range, 19-74 years). Operative time was similar between standard-pressure group (47.8 +/- 16.8 min) and low-pressure group (53.6 +/- 25.1). Moreover, intra-operative IV volume administration and urine output did not differ significantly between the 2 groups (p > 0.05). Although the average heart rate and mean arterial pressure were slightly higher in a standard-pressure group compared with a low-pressure group, serial measurements of these parameters were statistically similar between the 2 groups. Serial changes of serum levels of cortisol, glucose, adrenaline, and CRP were compared between surgery day, postoperative 6-h and 1st postoperative day, which did not differ significantly between the standard-pressure and the low-pressure groups (p > 0.05). CONCLUSION: Our study did not reveal any alteration in systemic stress response with reduction in intra-abdominal pressure of pneumoperitoneum in LC. RCT REGISTRATION: irct.ir ID: IRCT201110072982N5. PMID- 26892714 TI - Surgical outcomes in patients with intraoperative Electrocorticography (EcoG) guided epilepsy surgery-experiences of a tertiary care centre in India. AB - INTRODUCTION: The Comprehensive Epilepsy Surgery Program was started in 2001 at K.E.M. Hospital, Mumbai with the aim of performing epilepsy surgeries at highly concessional rates. We have started using intraoperative Electrocorticography (EcoG) since 2009 in patients with tumors, Mesial Temporal Sclerosis (MTS) plus and focal cortical dysplasia (FCD). This study highlights our experience with EcoG and it's utility in epilepsy surgery.introduction METHODS: 51 patients with drug resistant epilepsy due to temporal and extra-temporal tumors, MTS plus and FCD underwent pre-surgical evaluation and ECoG guided epilepsy surgery through our program. The surgical procedures employed included intraoperative EcoG guided lesionectomy or a lesionectomy with Anterior Temporal Lobectomy (ATL). Postoperative MRI and EEG were done. Seizure freedom was categorized as per Engel's classification. RESULTS: At a mean follow up of 33 months (range: 14-69 months), 43 out of 51(84.31%) patients were completely seizure free post-surgery (Engel's Class I). Among the patients who were not seizure free, 3 patients were in Engel's Class II and 5 patients were in Engel's Class III. Presence of a residual lesion on postoperative MRI (p < 0.001), abnormal postoperative EEG (p < 0.001) and persistent spikes on post-resection EcoG (p < 0.05) had a significant statistical association with poor seizure freedom post-surgery. CONCLUSION: The success of epilepsy surgery depends upon accurate localization and complete resection of the epileptogenic tissue, both of which are aided by intraoperative EcoG.Thus, intraoperative EcoG is a useful adjunct in epilepsy surgery to achieve optimal seizure freedom in cases of MTS plus, focal cortical dysplasia and tumors. Even the patients who are not seizure free can achieve worthwhile improvement post surgery. PMID- 26892716 TI - Monitoring eruption activity using temporal stress changes at Mount Ontake volcano. AB - Volcanic activity is often accompanied by many small earthquakes. Earthquake focal mechanisms represent the fault orientation and slip direction, which are influenced by the stress field. Focal mechanisms of volcano-tectonic earthquakes provide information on the state of volcanoes via stresses. Here we demonstrate that quantitative evaluation of temporal stress changes beneath Mt. Ontake, Japan, using the misfit angles of focal mechanism solutions to the regional stress field, is effective for eruption monitoring. The moving average of misfit angles indicates that during the precursory period the local stress field beneath Mt. Ontake was deviated from the regional stress field, presumably by stress perturbations caused by the inflation of magmatic/hydrothermal fluids, which was removed immediately after the expulsion of volcanic ejecta. The deviation of the local stress field can be an indicator of increases in volcanic activity. The proposed method may contribute to the mitigation of volcanic hazards. PMID- 26892715 TI - Mechanical thrombectomy by Solitaire stent for treating acute ischemic stroke: A prospective cohort study. AB - BACKGROUND: Acute ischemic stroke (AIS) is a worldwide serious health problem. Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt PA) is the standard treatment; however, only a small number of patients benefit from it due to the strict application restrictions. Recently, more and more evidence prove mechanical thrombectomy is an effective and safe therapy of AIS. PATIENTS AND METHODS: From December 2010 to March 2015, 83 patients who underwent mechanical thrombectomy were collected as a sample pool. All patients met the following criteria: National Institutes of Health Stroke Scale (NIHSS) score >=10, treatment performed within 6 h from the onset of symptoms, no large hypodensity on CT or multimodal MRI, and angiography revealed occlusion of a major cerebral artery. Recanalization rates were assessed immediately post procedure by follow-up angiography according to the thrombolysis in cerebral infarction score criteria. Assessment of the modified Rankin Scale was performed 90 days after treatment. RESULTS: The mean age of patients was 63.3 years, and NIHSS scores 19.12 +/- 4.60 at presentation. The vessel occlusions occurred in the middle cerebral artery (68.7%), distal internal carotid artery (7.2%), internal carotid artery with tandem middle cerebral artery occlusion (14.5%), basilar artery (2.4%), and vertebral artery (7.2%). Successful recanalization (TICI 3/2b) was achieved in 56 of 83 patients (67.5%). At 90-day follow-up, good clinical outcome (mRS <= 2) was achieved in 33 of 83 patients (39.8%), while 20 patients died (24.1%). CONCLUSIONS: This study revealed mechanical thrombectomy with Solitaire stent device was an effective and safe therapy, which achieved a high rate of angiographic recanalization and independent outcome accompanied by a low mortality rate. PMID- 26892717 TI - Size of silver nanoparticles determines proliferation ability of human circulating lymphocytes in vitro. AB - In this work we present biological effects of silver nanoparticles (AgNPs) synthesized by picosecond laser ablation of silver in deionized water. We examined induction of chromosomal aberrations, lymphocyte micronuclei, appearance and recovery of double strand breaks (DSBs) of DNA, cell proliferation potential, concentration of lipid peroxidation products and insulin-like growth factor 1 (ILGF-1). We found that AgNPs sized from 3 nm to 8 nm induce cell cytostasis, which is accompanied with its clastogenic action on DNA, while AgNPs, sized 2 nm behaves contrary stimulating cell proliferation by enhancing ILGF-1 concentration. PMID- 26892718 TI - Toxicokinetics and tissue distribution of titanium in ionic form after intravenous and oral administration. AB - Titanium is widely used both in food and cosmetics, as well as in surgery and industry. Contrary to most studies, the present work focused on the determination of the toxicokinetic parameters of titanium in ionic form, as well as on its tissue biodistribution in rats. The animals were administered either a single intravenous dose of 6 mg Ti/kg b.w., or received the same dose orally every day for 30 days. The concentration of titanium in the serum and organs was measured by a graphite furnace atomic absorption spectrometry. Metal rapidly distributed from the circulation to the investigated organs after both routes of administration, and kidney was identified as the main target tissue, followed by liver and spleen. One month of oral exposure to Ti led to the increase of its concentration in liver, kidneys, spleen, and heart. In the intravenous study, both the highest area under concentration-time curves and the longest elimination half-life time were recorded in the kidney followed by serum, spleen and liver. The present study contributes to the knowledge of the toxicokinetics of titanium in ionic form, which may be especially useful when assessing the health risks of long-term exposure to titanium alloy implants in patients. PMID- 26892719 TI - Mouse tissue distribution and persistence of the food-born fusariotoxins Enniatin B and Beauvericin. AB - The fusariotoxins Enniatin B (Enn B) and Beauvericin (Bea) have recently aroused interest as food contaminants and as potential anticancer drugs. However, limited data are available about their toxic profile. Aim of this study was to investigate their pharmacological behavior in vivo and their persistence in mice. Therefore, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to analyze the distribution of Enn B and Bea in selected tissue samples and biological fluids originating from mice treated intraperitoneally with these cyclohexadepsipeptides. Overall, no toxicological signs during life time or pathological changes were observed. Moreover, both fusariotoxins were found in all tissues and serum but not in urine. Highest amounts were measured in liver and fat demonstrating the molecules tendency to bioaccumulate in lipophilic tissues. While for Bea no metabolites could be detected, for Enn B three phase I metabolites (dioxygenated-Enn B, mono- and di-demethylated-Enn B) were found in liver and colon, with dioxygenated-Enn B being most prominent. Consequently, contribution of hepatic as well as intestinal metabolism seems to be involved in the overall metabolism of Enn B. Thus, despite their structural similarity, the metabolism of Enn B and Bea shows distinct discrepancies which might affect long term effects and tolerability in humans. PMID- 26892720 TI - Bacillus amyloliquefaciens SQR9 induces dendritic cell maturation and enhances the immune response against inactivated avian influenza virus. AB - The objective of this study was to evaluate the stimulatory effects of Bacillus amyloliquefaciens SQR9 on dendritic cells (DCs) and to verify its ability to enhance the immune response by modulating DC maturation. The results demonstrated that B. amyloliquefaciens SQR9 can adhere to the nasal epithelium and be taken up by DCs in the nasal mucosa, thereby inducing DC maturation and resulting in increased CD80, CD86, CD40 and MHCII expression and cytokine secretion. The frequencies of CD4(+) and CD8(+) T cells and CD69(+) memory T cells were increased in spleens after nasal immunization with virus plus B. amyloliquefaciens SQR9 compared to immunization with inactivated H9N2 AIV alone. Moreover, the levels of sIgA in the nasal cavity, the trachea, and the lung and the levels of IgG, IgG1, and IgG2a in serum were significantly increased in mice administered WIV plus SQR9 compared to mice administered H9N2 WIV alone. The results of this study demonstrated that B. amyloliquefaciens SQR9 can stimulate DC maturation to effectively induce an immune response. In conclusion, an effective immune response may result from the uptake of H9N2 by DCs in the nasal mucosa, thereby stimulating DC maturation and migration to cervical lymph nodes to initiate immune response. PMID- 26892722 TI - Derivation of motor neuron-like cells from neonatal mouse testis in a simple culture condition. AB - Embryonic stem cell (ESC) therapy is an exciting way to treat neurodegenerative disease and central nervous system injury. However, many ethical and immunological problems surround the use of embryonic stem cells. Finding an alternative source of stem cells is therefore pertinent. In this study, spermatogonia stem cells (SSCs) were used to generate mature motor neurons. SSCs were extracted from neonatal testes and cultured in DMED/F12 medium for 3 weeks. Characterisation of SSC-derived ESC-like cells was confirmed by RT-qPCR, immunostaining, alkaline phosphatase activity and their ability to form embryoid bodies (EBs). The EBs were induced by retinoic acid and Sonic hedgehog and trypsinised to obtain single induced cells. The single cells were cultured in neural medium for 18 days. Characterisation of neural precursors and motor neuron like cells was confirmed by RT-qPCR and immunocytochemical analysis at the 7th day (early stage) and 18th day (late stage), respectively, of culturing. The neural precursors were found to be positive for nestin and Sox2, and a small fraction of cells expressed beta-tubulin III. Upon further differentiation, multipolar neurons were detected that expressed beta-tubulin III and MAP2 markers. Moreover, the expression levels of Olig2 and PAX6 were significantly lower, while HB9, Isl1 and Isl2 expression levels were higher at the late stage when compared to the early stage. These results show that SSCs have the potential to differentiate to motor neuron-like cells and express markers specific for mature motor neurons. However, the functional ability of these cells remains to be evaluated in future studies. PMID- 26892723 TI - Response to Shelton, F. et al., procedures of limited clinical value in ENT: what effect has there been on operating numbers? PMID- 26892721 TI - Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity Reactions. AB - IgG4 is the least abundant IgG subclass in human serum, representing less than 5% of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcgammaRIIb, which can negatively regulate FcepsilonRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE mediated allergic responses. PMID- 26892724 TI - Consistency between verbal and non-verbal affective cues: a clue to speaker credibility. AB - Listeners are exposed to inconsistencies in communication; for example, when speakers' words (i.e. verbal) are discrepant with their demonstrated emotions (i.e. non-verbal). Such inconsistencies introduce ambiguity, which may render a speaker to be a less credible source of information. Two experiments examined whether children make credibility discriminations based on the consistency of speakers' affect cues. In Experiment 1, school-age children (7- to 8-year-olds) preferred to solicit information from consistent speakers (e.g. those who provided a negative statement with negative affect), over novel speakers, to a greater extent than they preferred to solicit information from inconsistent speakers (e.g. those who provided a negative statement with positive affect) over novel speakers. Preschoolers (4- to 5-year-olds) did not demonstrate this preference. Experiment 2 showed that school-age children's ratings of speakers were influenced by speakers' affect consistency when the attribute being judged was related to information acquisition (speakers' believability, "weird" speech), but not general characteristics (speakers' friendliness, likeability). Together, findings suggest that school-age children are sensitive to, and use, the congruency of affect cues to determine whether individuals are credible sources of information. PMID- 26892725 TI - Risk Prediction Modeling of Sequencing Data Using a Forward Random Field Method. AB - With the advance in high-throughput sequencing technology, it is feasible to investigate the role of common and rare variants in disease risk prediction. While the new technology holds great promise to improve disease prediction, the massive amount of data and low frequency of rare variants pose great analytical challenges on risk prediction modeling. In this paper, we develop a forward random field method (FRF) for risk prediction modeling using sequencing data. In FRF, subjects' phenotypes are treated as stochastic realizations of a random field on a genetic space formed by subjects' genotypes, and an individual's phenotype can be predicted by adjacent subjects with similar genotypes. The FRF method allows for multiple similarity measures and candidate genes in the model, and adaptively chooses the optimal similarity measure and disease-associated genes to reflect the underlying disease model. It also avoids the specification of the threshold of rare variants and allows for different directions and magnitudes of genetic effects. Through simulations, we demonstrate the FRF method attains higher or comparable accuracy over commonly used support vector machine based methods under various disease models. We further illustrate the FRF method with an application to the sequencing data obtained from the Dallas Heart Study. PMID- 26892727 TI - The contribution of protein intrinsic disorder to understand the role of genetic variants uncovered by autism spectrum disorders exome studies. AB - Several autism spectrum disorders (ASD) exome studies suggest that coding single nucleotide variants (SNVs) play an important role on ASD etiology. Usually, the pathogenic effect of missense mutations is estimated through predictors that lose accuracy for those SNVs placed in intrinsically disordered regions of protein. Here, we used bioinformatics tools to investigate the effect of mutations described in ASD published exome studies (549 mutations) in protein disorder, considering post-translational modification, PEST and Molecular Recognition Features (MoRFs) motifs. Schizophrenia and type 2 diabetes (T2D) datasets were created for comparison purposes. The frequency of mutations predicted as disordered was comparable among the three datasets (38.1% in ASD, 35.7% in schizophrenia, 46.4% in T2D). However, the frequency of SNVs predicted to lead a gain or loss of functional sites or change intrinsic disorder tendencies was higher in ASD and schizophrenia than T2D (46.9%, 36.4%, and 23.1%, respectively). The results obtained by SIFT and PolyPhen-2 indicated that 38.9% and 34.4% of the mutations predicted, respectively, as tolerated and benign showed functional alterations in disorder properties. Given the frequency of mutations placed in IDRs and their functional impact, this study suggests that alterations in intrinsic disorder properties might play a role in ASD and schizophrenia etiologies. They should be taken into consideration when researching the pathogenicity of mutations in neurodevelopmental and psychiatric diseases. Finally, mutations with functional alterations in disorder properties must be potential targets for in vitro and in vivo functional studies. PMID- 26892728 TI - Three-dimensional printing models in surgery. PMID- 26892726 TI - Whole-genome mutational burden analysis of three pluripotency induction methods. AB - There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming methods: integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs. We used whole-genome sequencing and de novo genome mapping to identify single nucleotide variants, insertions and deletions, and structural variants. Our results show a moderate number of variants in the iPSCs that were not evident in the parental fibroblasts, which may result from reprogramming. There were only small differences in the total numbers and types of variants among different reprogramming methods. Most importantly, a thorough genomic analysis showed that the variants were generally benign. We conclude that the process of reprogramming is unlikely to introduce variants that would make the cells inappropriate for therapy. PMID- 26892729 TI - Independent prognostic factors and unsettled parameters of resected primary gastrointestinal stromal tumors. PMID- 26892730 TI - Pharmacological Effects of RAAS Blockade in Ischemic Nephropathy. AB - BACKGROUND: The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies have led to a renewed focus on pharmacological strategies promoting blood pressure control and renal protection. It is essential to further elucidate the pathophysiological mechanisms underlying hypoperfusion induced renal microvascular dysfunction with subsequent tissue injury and fibrogenesis. The role of renin angiotensin aldosterone system as a mediator of the main pathophysiological consequences of ischemic nephropathy is well known. However, more recent experimental evidence on the adrenergic system and intrarenal tubular feedback mechanisms has stimulated new interest towards a multi-target therapeutic approach. METHODS: This review focuses on the pharmacology of the principle therapeutic drug classes currently used in the treatment of atherosclerotic renal artery stenosis with an analysis of their metabolic aspects and use in clinical practice based on evidence from clinical trials. RESULTS AND CONCLUSIONS: An optimal pharmacologic approach is crucial for a successful prevention of renal injury and cardiovascular events in this high-risk population. Antihypertensive treatment should include renin angiotensin aldosterone system blockade medication not only for their antihypertensive properties, but especially for those cardio and renoprotective. PMID- 26892731 TI - A Comparison of Non-Human Primate Cytochrome P450 2D Members and the Implication in Drug Discovery. AB - BACKGROUND: Non-human primates are valuable animal models in drug discovery and biomedical research. Human CYP2D6 accounts for 1.3-4.3% of total hepatic CYP content in the liver, but is involved in the metabolism of more than 150 drugs. With the advancement of genomic sequencing and annotation, a panel of CYP2D genes have been cloned from non-human primates. This review highlights the similarities and differences of these CYP2D genes non-human primates. METHODS: We conducted a structured PubMed search using a focused review question and proper inclusion/exclusion criteria. The quality of retrieved papers was assessed and briefed using standard tools and expert knowledge. RESULTS: Most studies on CYP expression in non-human primates have been carried out in the cynomolgus and Rhesus monkeys. Deduced amino acid sequences of primate CYP2D cDNAs share high sequence identity (93-96%) with human CYP2D6. The chimpanzee genome has CYP2D6 and 2D7 but bonobos only contain CYP2D6. The CYP2D6 gene is located on chromosome 22 in the chimpanzee genome (human CYP2D6 maps to chromosome 22q13.1), and on chromosome 10 in the genome of the Rhesus monkey. Cynomolgus monkey CYP2D17 and Japanese monkey 2D29 metabolize bufuralol and dextromethorphan. CYP2D17 metabolizes bufuralol and dextromethorphan, whereas CYP2D29 metabolizes bufuralol and debrisoquine. In addition, quinidine inhibits both cynomolgus monkey CYP2D17 and Japanese monkey 2D29. CONCLUSION: The CYP2D members from non-human primates show differential genomic contexts, catalytic activities toward substrates and inhibitory profiles. Further studies are warranted to elucidate the structural and functional features of CYP2D members in non-human primates and thus offer a solid base for the application of these animals in drug discovery. PMID- 26892732 TI - Genomic Variations Affecting Biological Effects of Statins. AB - BACKGROUND: Statins are inhibitors of hydroxy-methyl-glutaryl coenzymeA (HMG-CoA) reductase, the rate-limiting enzyme involved in de novo cholesterol synthesis. The patient health profile needs to be taken in account during the interpretation of the variability in the outcome of drug therapy, as well as compliance with prescribed pharmacological treatments, and genetic profile. OBJECTIVE: Several genetic polymorphisms playing a role in the different response to lipid lowering therapy have recently been identified. Statins, today are used to reduce Low Density Lipoprotein-Cholesterol (LDL-C), represent the treatment of choice in individuals with increased risk of Cardio-Vascular Disease (CVD), both in primary and secondary prevention of cardiovascular events. Regardless of the usefulness in a wide range of patients, the common interindividual genetic variability, along with phenotypic aspects, lead to resistance and adverse responses. METHODS: we reviewed on PubMed, inserting as term search "statin and polymorphism", "statin and pharmacogenomic", "statin and gene", "HMG-CoA reductase and gene". RESULTS: A large number of candidate genes and many single nucleotide polymorphisms (SNPs) have been evaluated and related to pharmacokinetic and/or pharmacodynamic of statins. CONCLUSION: Despite these several findings there is still not enough evidence to recommend pharmacogenomic tests before starting statin therapy. PMID- 26892733 TI - Sulfotransferase 1A1 as a Biomarker for Susceptibility to Carcinogenesis: From Molecular Genetics to the Role of Dietary Flavonoids. AB - BACKGROUND: Sulfotransferase (SULT) 1A1 is a phase II metabolic enzyme that catalyzes sulfate conjugation of various phenolic compounds, including endogenous substances, such as estrogens and thyroid hormones, but also different xenobiotics. Although sulfation is classically considered as a detoxification event facilitating the excretion of more water soluble metabolites from the body, in some cases such bioconversion may also lead to bioactivation of promutagens, producing highly reactive intermediates which are capable of damaging DNA and promoting carcinogenesis. The most common polymorphism in SULT1A1 (Arg213His) has an important functional impact by affecting the capacity to sulfate diverse substrates and numerous case-control studies have shown associations between SULT1A1 variants and susceptibility to different malignancies. Several factors may significantly influence such relationships, including ethnicity, gender, parity, menopausal status, use of estrogen replacement therapy, exposure to tobacco smoke or occupational chemicals. RESULTS AND CONCLUSION: In this review article, we show that one more important determinant should be considered as a stratifying factor in studies of possible associations between SULT1A1 variants and cancer risk, i.e., the dietary intake of different flavonoids. As sulfation of bioactive plant polyphenols can change their potential anticancer activities and, on the other hand, these phytochemicals are capable to behave also as potent SULT1A1 inhibitors, the regular dietary exposure of humans to these compounds can make a great contribution to the impact of sulfation capacity on individual susceptibility to carcinogenesis. The effect of specific flavonoids as well as their interactions with other factors on associations between SULT1A1 alleles and cancer risk certainly needs further thorough studies. PMID- 26892735 TI - Copper-Catalyzed S-C/S-N Bond Interconversions. AB - Under an atmosphere of dioxygen, copper-catalyzed de-alkylation/amination sequences provide sulfonimidamides from unprotected sulfoximines in moderate to good yields. Mechanistic studies suggest the involvement of radicals in both the C-S bond cleavage and the formation of the new N-S bond. PMID- 26892734 TI - Quantitative BOLD imaging at 3T: Temporal changes in hepatocellular carcinoma and fibrosis following oxygen challenge. AB - PURPOSE: To evaluate the utility of oxygen challenge and report on temporal changes in blood oxygenation level-dependent (BOLD) contrast in normal liver, hepatocellular carcinoma (HCC) and background fibrosis. MATERIALS AND METHODS: Eleven volunteers (nine male and two female, mean age 33.5, range 27-41 years) and 10 patients (nine male and one female, mean age 68.9, range 56-87 years) with hepatocellular carcinoma on a background of diffuse liver disease were recruited. Imaging was performed on a 3T system using a multiphase, multiecho, fast gradient echo sequence. Oxygen was administered via a Hudson mask after 2 minutes of free breathing. Paired t-tests were performed to determine if the mean pre- and post O2 differences were statistically significant. RESULTS: In patients with liver fibrosis (n = 8) the change in T2* following O2 administration was elevated (0.88 +/- 0.582 msec, range 0.03-1.69 msec) and the difference was significant (P = 0.004). The magnitude of the BOLD response in patients with HCC (n = 10) was larger, however the response was more variable (1.07 +/- 1.458 msec, range -0.93 3.26 msec), and the difference was borderline significant (P = 0.046). The BOLD response in the volunteer cohort was not significant (P = 0.121, 0.59 +/- 1.162 msec, range -0.81-2.44 msec). CONCLUSION: This work demonstrates that the BOLD response following oxygen challenge within cirrhotic liver is consistent with a breakdown in vascular autoregulatory mechanisms. Similarly, the elevated BOLD response within HCC is consistent with the abnormal capillary vasculature within tumors and the arterialization of the blood supply. Our results suggest that oxygen challenge may prove a viable BOLD contrast mechanism in the liver. J. Magn. Reson. Imaging 2016;44:739-744. PMID- 26892737 TI - HPV vaccine: Less is more. PMID- 26892736 TI - The phenomenon of acquired resistance to metformin in breast cancer cells: The interaction of growth pathways and estrogen receptor signaling. AB - Metformin, a biguanide antidiabetic drug, is used to decrease hyperglycemia in patients with type 2 diabetes. Recently, the epidemiological studies revealed the potential of metformin as an anti-tumor drug for several types of cancer, including breast cancer. Anti-tumor metformin action was found to be mediated, at least in part, via activation of adenosine monophosphate-activated protein kinase (AMPK)-intracellular energy sensor, which inhibits the mammalian target of rapamycin (mTOR) and some other signaling pathways. Nevertheless, some patients can be non-sensitive or resistant to metformin action. Here we analyzed the mechanism of the formation of metformin-resistant phenotype in breast cancer cells and its role in estrogen receptor (ER) regulation. The experiments were performed on the ER-positive MCF-7 breast cancer cells and metformin-resistant MCF-7 subline (MCF-7/M) developed due to long-term metformin treatment. The transcriptional activity of NF-kappaB and ER was measured by the luciferase reporter gene analysis. The protein expression was determined by immunoblotting (Snail1, (phospho)AMPK, (phospho)IkappaBalpha, (phospho)mTOR, cyclin D1, (phospho)Akt and ERalpha) and immunohistochemical analysis (E-cadherin). We have found that: 1) metformin treatment of MCF-7 cells is accompanied with the stimulation of AMPK and inhibition of growth-related proteins including IkappaBalpha, NF-kappaB, cyclin D1 and ERalpha; 2) long-term metformin treatment lead to the appearance and progression of cross-resistance to metformin and tamoxifen; the resistant cells are characterized with the unaffected AMPK activity, but the irreversible ER suppression and constitutive activation of Akt/Snail1 signaling; 3) Akt/Snail1 signaling is involved into progression of metformin resistance. The results presented may be considered as the first evidence of the progression of cross-resistance to metformin and tamoxifen in breast cancer cells. Importantly, the acquired resistance to both drugs is based on the constitutive activation of Akt/Snail1/E-cadherin signaling that opens new perspectives to overcome the metformin/tamoxifen resistance of breast cancer. PMID- 26892738 TI - Protective efficacy afforded by live Pasteurella multocida vaccines in chickens is independent of lipopolysaccharide outer core structure. AB - Pasteurella multocida is a major animal pathogen that causes a range of diseases including fowl cholera. P. multocida infections result in considerable losses to layer and breeder flocks in poultry industries worldwide. Both killed whole-cell and live-attenuated vaccines are available; these vaccines vary in their protective efficacy, particularly against heterologous strains. Moreover, until recently there was no knowledge of P. multocida LPS genetics and structure to determine precisely how LPS structure affects the protective capacity of these vaccines. In this study we show that defined lipopolysaccharide (LPS) mutants presented as killed whole-cell vaccines elicited solid protective immunity only against P. multocida challenge strains expressing highly similar or identical LPS structures. This finding indicates that vaccination of commercial flocks with P. multocida killed cell formulations will not protect against strains producing an LPS structure different to that produced by strains included in the vaccine formulation. Conversely, protective immunity conferred by vaccination with live P. multocida strains was found to be largely independent of LPS structure. Birds vaccinated with a range of live mutants belonging to the L1 and L3 LPS genotypes, each expressing a specific truncated LPS structure, were protected against challenge with the parent strain. Moreover, birds vaccinated with any of the five LPS mutants belonging to the L1 LPS genotype were also protected against challenge with an unrelated strain and two of the five groups vaccinated with live LPS mutants belonging to the L3 genotype were protected against challenge with an unrelated strain. In summary, vaccination with live P. multocida aroA mutants producing full-length L1 or L3 LPS or vaccination with live strains producing shortened L1 LPS elicited strong protective immunity against both homologous and heterologous challenge. PMID- 26892739 TI - The cost-utility of integrated cervical cancer prevention strategies in the Ontario setting - Can we do better? AB - INTRODUCTION: A universal, publicly funded, school-based human papillomavirus (HPV) vaccination program in grade eight girls was initiated in Ontario in 2007. We present a cost-utility analysis of integrated cervical cancer prevention programs from the healthcare payer perspective. METHODS: Our analysis was based on linked HPV transmission and disease history models. We obtained data from the literature, provincial surveys and Ontario population-based linked health administrative datasets. We modeled combinations of vaccination and screening strategies. We considered vaccination based on the Ontario experience, as well as conservative and optimistic scenarios, varying coverage, vaccine effectiveness and duration of protection. We considered 900 screening scenarios (screening start age: 21-70 years, screening interval: 3-20 years; 1-year time steps). The current schedule screens every 3 years starting at age 21 years. We examined (1) first vaccinated cohort (low herd-immunity), and (2) steady state, i.e. all cohorts were vaccinated (high herd-immunity). RESULTS: Adding vaccination to the current screening schedule was cost-effective (= 17 mmol/L prompted 86.0%-93.8% of respondents to adopt a treat-and-defer strategy, while a level >= 23 mmol/L prompted 86.0%-96.9% of respondents to cancel the cataract surgery. The respondents were consistently more concerned about perioperative hyperglycaemia (n = 99, 76.7%) than intraoperative hypoglycaemia (n = 83, 64.3%). CONCLUSION: The current study presented the prevalent practice patterns of ophthalmologists and anaesthesiologists in the perioperative management of diabetic patients undergoing cataract surgery in four public hospitals in Singapore. Further research in this field is required, and may be useful for the future formulation of formal guidelines and protocols. PMID- 26892743 TI - Memory effects of sedative drugs in children and adolescents--protocol for a systematic review. AB - BACKGROUND: Some sedatives used in children and adolescents can affect memory function. Memory impairment of traumatic experience can minimize the chance of future psychological trauma. Knowledge about the potential of different sedatives to produce amnesia can help in the decision-making process of choosing a sedative regimen. The aim of this systematic review is to evaluate the effect of different sedatives on memory of perioperative events in children and adolescents. METHODS/DESIGN: Electronic databases and other sources, such as trial registers, gray literature, and conference abstracts will be searched. Randomized controlled trials will be included that assess memory of perioperative events in children and adolescents 2-19 years old receiving sedative drugs as premedication or as agents for procedural sedation in a medical or dental settings. The outcomes will be loss of memory after and before sedative administration (anterograde and retrograde amnesia). Two independent reviewers will perform screening, study selection, and data extraction. Disagreement at all levels will be resolved by consensus or by involving a third reviewer. Assessment of the risk of bias of included studies will be performed according to "Cochrane Collaboration's Tool for Assessing Risk of Bias in Randomized Trials." Clinical and methodological heterogeneity across studies will be evaluated to determine if it is possible to combine or not combine study results in a meta-analysis. DISCUSSION: To the best of our knowledge, there is no systematic review that specifically addresses this question. Findings from the review will be useful in the decision-making process about the best sedative for minimizing recall of the medical/dental event and possible psychological trauma. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017559. PMID- 26892744 TI - Transanal minimally invasive surgery approach for rectal GIST. PMID- 26892746 TI - A method of coupling the Paterno-Buchi reaction with direct infusion ESI-MS/MS for locating the C[double bond, length as m-dash]C bond in glycerophospholipids. AB - Tandem mass spectrometry (MS/MS) coupled with soft ionization is established as an essential platform for lipid analysis; however, determining high order structural information, such as the carbon-carbon double bond (C[double bond, length as m-dash]C) location, remains challenging. Recently, our group demonstrated a method for sensitive and confident lipid C[double bond, length as m-dash]C location determination by coupling online the Paterno-Buchi (PB) reaction with nanoelectrospray ionization (nanoESI) and MS/MS. Herein, we aimed to expand the scope of the PB reaction for lipid analysis by enabling the reaction with infusion ESI-MS/MS at much higher flow rates than demonstrated in the nanoESI setup (~20 nL min(-1)). In the new design, the PB reaction was effected in a fused silica capillary solution transfer line, which also served as a microflow UV reactor, prior to ESI. This setup allowed PB reaction optimization and kinetics studies. Under optimized conditions, a maximum of 50% PB reaction yield could be achieved for a standard glycerophosphocholine (PC) within 6 s of UV exposure over a wide flow rate range (0.1-10 MUL min(-1)). A solvent composition of 7 : 3 acetone : H2O (with 1% acid or base modifier) allowed the highest PB yields and good lipid ionization, while lower yields were obtained with an addition of a variety of organic solvents. Radical induced lipid peroxidation was identified to induce undesirable side reactions, which could be effectively suppressed by eliminating trace oxygen in the solution via N2 purge. Finally, the utility of coupling the PB reaction with infusion ESI-MS/MS was demonstrated by analyzing a yeast polar lipid extract where C[double bond, length as m-dash]C bond locations were revealed for 35 glycerophospholipids (GPs). PMID- 26892745 TI - Plant-Derived and Endogenous Cannabinoids in Epilepsy. AB - Cannabis is one of the oldest psychotropic drugs and its anticonvulsant properties have been known since the last century. The aim of this review was to analyze the efficacy of cannabis in the treatment of epilepsy in adults and children. In addition, a description of the involvement of the endocannabinoid system in epilepsy is given in order to provide a biochemical background to the effects of endogenous cannabinoids in our body. General tolerability and adverse events associated with cannabis treatment are also investigated. Several anecdotal reports and clinical trials suggest that in the human population cannabis has anticonvulsant properties and could be effective in treating partial epilepsies and generalized tonic-clonic seizures, still known as "grand mal." They are based, among other factors, on the observation that in individuals who smoke marijuana to treat epilepsy, cessation of cannabis use precipitates the re emergence of convulsive seizures, whereas resuming consumption of this psychotropic drug controls epilepsy in a reproducible manner. In conclusion, there is some anecdotal evidence for the potential efficacy of cannabis in treating epilepsy. Though there has been an increased effort by patients with epilepsy, their caregivers, growers, and legislators to legalize various forms of cannabis, there is still concern about its efficacy, relative potency, availability of medication-grade preparations, dosing, and potential short- and long-term side effects, including those on prenatal and childhood development. PMID- 26892747 TI - A novel holistic framework for genetic-based captive-breeding and reintroduction programs. AB - Research in reintroduction biology has provided a greater understanding of the often limited success of species reintroductions and highlighted the need for scientifically rigorous approaches in reintroduction programs. We examined the recent genetic-based captive-breeding and reintroduction literature to showcase the underuse of the genetic data gathered. We devised a framework that takes full advantage of the genetic data through assessment of the genetic makeup of populations before (past component of the framework), during (present component), and after (future component) captive-breeding and reintroduction events to understand their conservation potential and maximize their success. We empirically applied our framework to two small fishes: Yarra pygmy perch (Nannoperca obscura) and southern pygmy perch (Nannoperca australis). Each of these species has a locally adapted and geographically isolated lineage that is endemic to the highly threatened lower Murray-Darling Basin in Australia. These two populations were rescued during Australia's recent decade-long Millennium Drought, when their persistence became entirely dependent on captive-breeding and subsequent reintroduction efforts. Using historical demographic analyses, we found differences and similarities between the species in the genetic impacts of past natural and anthropogenic events that occurred in situ, such as European settlement (past component). Subsequently, successful maintenance of genetic diversity in captivity-despite skewed brooder contribution to offspring-was achieved through carefully managed genetic-based breeding (present component). Finally, genetic monitoring revealed the survival and recruitment of released captive-bred offspring in the wild (future component). Our holistic framework often requires no additional data collection to that typically gathered in genetic-based breeding programs, is applicable to a wide range of species, advances the genetic considerations of reintroduction programs, and is expected to improve with the use of next-generation sequencing technology. PMID- 26892749 TI - Fair Balance and Adequate Provision in Direct-to-Consumer Prescription Drug Online Banner Advertisements: A Content Analysis. AB - BACKGROUND: The current direct-to-consumer advertising (DTCA) guidelines were developed with print, television, and radio media in mind, and there are no specific guidelines for online banner advertisements. OBJECTIVE: This study evaluates how well Internet banner ads comply with existing Food and Drug Administration (FDA) guidelines for DTCA in other media. METHODS: A content analysis was performed of 68 banner advertisements. A coding sheet was developed based on (1) FDA guidance documents for consumer-directed prescription drug advertisements and (2) previous DTCA content analyses. Specifically, the presence of a brief summary detailing the drug's risks and side effects or of a "major statement" identifying the drug's major risks, and the number and type of provisions made available to consumers for comprehensive information about the drug were coded. In addition, the criterion of "fair balance," the FDA's requirement that prescription drug ads balance information relating to the drug's risks with information relating to its benefits, was measured by numbering the benefit and risk facts identified in the ads and by examining the presentation of risk and benefit information. RESULTS: Every ad in the sample included a brief summary of risk information and at least one form of adequate provision as required by the FDA for broadcast ads that do not give audiences a brief summary of a drug's risks. No ads included a major statement. There were approximately 7.18 risk facts for every benefit fact. Most of the risks (98.85%, 1292/1307) were presented in the scroll portion of the ad, whereas most of the benefits (66.5%, 121/182) were presented in the main part of the ad. Out of 1307 risk facts, 1292 were qualitative and 15 were quantitative. Out of 182 benefit facts, 181 were qualitative and 1 was quantitative. The majority of ads showed neutral images during the disclosure of benefit and risk facts. Only 9% (6/68) of the ads displayed positive images and none displayed negative images when presenting risks facts. When benefit facts were being presented, 7% (5/68) showed only positive images. No ads showed negative images when the benefit facts were being presented. CONCLUSIONS: In the face of ambiguous regulatory guidelines for online banner promotion, drug companies appear to make an attempt to adapt to regulatory guidelines designed for traditional media. However, banner ads use various techniques of presentation to present the advertised drug in the best possible light. The FDA should formalize requirements that drug companies provide a brief summary and include multiple forms of adequate provision in banner ads. PMID- 26892748 TI - Thermal energy storage characteristics of micro-nanoencapsulated heneicosane and octacosane with poly(methylmethacrylate) shell. AB - In this study, PMMA/heneicosane (C21) and PMMA/octacosane (C28) micro-nano capsules were fabricated via emulsion polymerisation method. The chemical structures of the fabricated capsules were verified with the FT-IR spectroscopy analysis. The results of POM, SEM and PSD analysis indicated that most of the capsules were consisted of micro/nano-sized spheres with compact surface. The DSC measurements showed that the capsules had melting temperature in the range of about 39-60 degrees C and latent heat energy storage capacity in the range of about 138-152 J/g. The results of TGA showed that sublimit temperature values regarding the first degradation steps of both capsules were quite over the phase change or working temperatures of encapsulated paraffins. The thermal cycling test exhibited that the capsules had good thermal reliability and chemical stability. Additionally, the prepared capsules had reasonably high thermal conductivity. PMID- 26892750 TI - A magnetic vehicle realized tumor cell-targeted radiotherapy using low-dose radiation. AB - Radiotherapy, a common cancer treatment, often adversely affects the surrounding healthy tissue and/or cells. Some tumor tissue-focused radiation therapies have been developed to lower radiation-induced lesion formation; however, achieving tumor cell-targeted radiotherapy (i.e., precisely focusing the radiation efficacy to tumor cells) remains a challenge. In the present study, we developed a novel tumor cell-targeted radiotherapy, named targeted sensitization-enhanced radiotherapy (TSER), that exploits tumor-specific folic acid-conjugated carboxymethyl lauryl chitosan/superparamagnetic iron oxide (FA-CLC/SPIO) micelles to effectively deliver chlorin e6 (Ce6, a sonosensitizer) to mitochondria of HeLa cells under magnetic guidance. For the in vitro tests, the sensitization of Ce6 induced by ultrasound, that could weaken the radiation resistant ability of tumor cells, occurred only in Ce6-internalizing tumor cells. Therefore, low-dose X-ray irradiation, that was not harmful to normal cells, could exert high tumor cell specific killing ability. The ratio of viable normal cells to tumor cells was increased considerably, from 7.8 (at 24h) to 97.1 (at 72h), after they had received TSER treatment. Our data suggest that TSER treatment significantly weakens tumor cells, resulting in decreased viability in vitro as well as decreased in vivo subcutaneous tumor growth in nude mice, while the adverse effects were minimal. Taken together, TSER treatment appears to be an effective, clinically feasible tumor cell-targeted radiotherapy that can solve the problems of traditional radiotherapy and photodynamic therapy. PMID- 26892751 TI - Fluorescence optical imaging in anticancer drug delivery. AB - In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. PMID- 26892752 TI - Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the art. AB - Glioblastoma multiforme, a grade IV glioma, is the most frequently occurring and invasive primary tumor of the central nervous system, which causes about 4% of cancer-associated-deaths, making it one of the most fatal cancers. With present treatments, using state-of-the-art technologies, the median survival is about 14 months and 2 year survival rate is merely 3-5%. Hence, novel therapeutic approaches are urgently necessary. However, most drug molecules are not able to cross the blood-brain barrier, which is one of the major difficulties in glioblastoma treatment. This review describes the features of blood-brain barrier, and its anatomical changes with different stages of tumor growth. Moreover, various strategies to improve brain drug delivery i.e. tight junction opening, chemical modification of the drug, efflux transporter inhibition, convection-enhanced delivery, craniotomy-based drug delivery and drug delivery nanosystems are discussed. Nanocarriers are one of the highly potential drug transport systems that have gained huge research focus over the last few decades for site specific drug delivery, including drug delivery to the brain. Properly designed nanocolloids are capable to cross the blood-brain barrier and specifically deliver the drug in the brain tumor tissue. They can carry both hydrophilic and hydrophobic drugs, protect them from degradation, release the drug for sustained period, significantly improve the plasma circulation half-life and reduce toxic effects. Among various nanocarriers, liposomes, polymeric nanoparticles and lipid nanocapsules are the most widely studied, and are discussed in this review. For each type of nanocarrier, a general discussion describing their composition, characteristics, types and various uses is followed by their specific application to glioblastoma treatment. Moreover, some of the main challenges regarding toxicity and standardized evaluation techniques are narrated in brief. PMID- 26892753 TI - Neuropsychological Functioning in Veterans with Posttraumatic Stress Disorder: Associations with Performance Validity, Comorbidities, and Functional Outcomes. AB - OBJECTIVES: Numerous studies have shown that individuals with posttraumatic stress disorder (PTSD) display reduced performances on neuropsychological tests, although most prior research has not adequately accounted for comorbidities or performance validity concerns that are common in this population and could partially account for the observed neurocognitive findings. Moreover, few studies have examined the functional implications of neuropsychological results in PTSD. METHODS: We examined neuropsychological functioning in 44 veterans with PTSD and 40 veteran trauma comparison (TC) participants with combat exposure and no PTSD. RESULTS: After excluding four veterans with PTSD for performance validity concerns, multivariate analyses of variance by neurocognitive domain revealed significantly worse performance by the PTSD group in the domains of speed of information processing (p=.035) and executive functions (p=.017), but no group differences in attention/working memory, verbal/language functioning, visuoconstruction, or episodic memory. Group differences by PTSD status were still present after covarying for depression, a history of head injuries, and substance use disorders. Executive functioning performance was associated with poorer self-reported occupational functioning and physical health-related quality of life, while speed of information processing performance was associated with poorer physical health-related quality of life. DISCUSSION: These results are generally consistent with a fronto-limbic conceptualization of PTSD-associated neuropsychological dysfunction and show that cognitive functioning may be associated with critical functional outcomes. Taken together, results suggest that consideration of neurocognitive functioning may enhance the clinical management of individuals with PTSD. PMID- 26892754 TI - Resonance assignment of an engineered amino-terminal domain of a major ampullate spider silk with neutralized charge cluster. AB - Spider dragline fibers are predominantly made out of the major ampullate spidroins (MaSp) 1 and 2. The assembly of dissolved spidroin into a stable fiber is highly controlled for example by dimerization of its amino-terminal domain (NRN) upon acidification, as well as removal of sodium chloride along the spinning duct. Clustered residues D39, E76 and E81 are the most highly conserved residues of the five-helix bundle, and they are hypothesized to be key residues for switching between a monomeric and a dimeric conformation. Simultaneous replacement of these residues by their non-titratable analogues results in variant D39N/E76Q/E81Q, which is supposed to fold into an intermediate conformation between that of the monomeric and the dimeric state at neutral pH. Here we report the resonance assignment of Latrodectus hesperus NRN variant D39N/E76Q/E81Q at pH 7.2 obtained by high-resolution triple resonance NMR spectroscopy. PMID- 26892755 TI - Long-range superharmonic Josephson current and spin-triplet pairing correlations in a junction with ferromagnetic bilayers. AB - The long-range spin-triplet supercurrent transport is an interesting phenomenon in the superconductor/ferromagnet () heterostructure containing noncollinear magnetic domains. Here we study the long-range superharmonic Josephson current in asymmetric junctions. It is demonstrated that this current is induced by spin triplet pairs - or + in the thick layer. The magnetic rotation of the particularly thin layer will not only modulate the amplitude of the superharmonic current but also realise the conversion between - and + . Moreover, the critical current shows an oscillatory dependence on thickness and exchange field in the layer. These effect can be used for engineering cryoelectronic devices manipulating the superharmonic current. In contrast, the critical current declines monotonically with increasing exchange field of the layer, and if the layer is converted into half-metal, the long-range supercurrent is prohibited but still exists within the entire region. This phenomenon contradicts the conventional wisdom and indicates the occurrence of spin and charge separation in present junction, which could lead to useful spintronics devices. PMID- 26892757 TI - Habitat-related specialization of lateral-line system morphology in a habitat generalist and a habitat-specialist New Zealand eleotrid. AB - An investigation of intraspecific habitat-related patterns of variation in oculoscapular lateral-line superficial neuromasts (SN) identified a decrease in the ratio of total SNs to pores, and a trend towards decreased asymmetry in SNs in the habitat-generalist common bully Gobiomorphus cotidianus from fluvial habitats compared to lacustrine habitats, suggesting habitat-related phenotypic variability. A greater ratio of pores to SNs, as well as less variation in the total number and asymmetry of SNs observed in the fluvial habitat-specialist redfin bully Gobiomorphus huttoni may provide further evidence of variations in the oculoscapular lateral-line morphology of fluvial habitat G. cotidianus individuals serving as adaptations to more turbulent environments. PMID- 26892756 TI - Development and Feasibility of a Specialty-Specific National Surgical Quality Improvement Program (NSQIP): The Head and Neck-Reconstructive Surgery NSQIP. AB - IMPORTANCE: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) serves the need for continual quality assessment in general surgery. Previously, no parallel mechanism specific to head and neck oncologic surgery existed. OBJECTIVE: To address the need for continual quality assessment in subspecialty surgery by adapting the ACS NSQIP platform for complex head and neck oncologic surgical procedures. DESIGN, SETTING, AND PARTICIPANTS: With an institutional ACS NSQIP team's guidance, surgeons from the departments of head and neck surgery and plastic and reconstructive surgery developed disease- and procedure-specific preoperative, intraoperative, and postoperative variables specific to head and neck surgery requiring reconstruction. Collection occurred with 100% sampling and standard ACS NSQIP 30-day follow-up. After a pilot period, long-term functional outcomes were added to this platform. A total of 312 patients underwent head and neck surgery requiring reconstruction at an academic medical center between August 1, 2012, and June 30, 2013. EXPOSURES: Development of a specialty-specific head and neck surgery ACS NSQIP platform. MAIN OUTCOMES AND MEASURES: The feasibility of adapting the ACS NSQIP platform to capture complex head and neck surgery metrics in all patients. RESULTS: Head and neck surgery-specific preoperative, intraoperative, and postoperative variables were added to the ACS NSQIP platform and evaluated in 312 patients (201 [64.4%] male). Only 42 patients (13.5%) had no preoperative risk factors, and 136 (43.6%) had 3 or more risk factors. The mean (SD) duration of operation was 9.4 (3.0) hours (range, 1.7-19.3 hours). The mean (SD) postoperative length of stay was 7.9 (4.7) days (range, 1-40 days), 58 patients (18.6%) had an unplanned return to the operating room, 23 patients (7.4%) were readmitted within 30 days, and 3 patients (1.0%) died within 30 days. More than half of the patients (160 [51.3%]) did not experience a postoperative occurrence. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first comprehensive complex oncologic surgery outcomes platform derived from ACS NSQIP methods. The initial pilot demonstrates the ability to systematically capture head and neck surgery-specific variables with complete sampling. With multi-institutional expansion, increased accrual, and long-term patient-reported outcomes, we hope to set risk-adjusted benchmarks that may underpin quality improvement efforts in complex head and neck surgery. PMID- 26892758 TI - High cortisol responders to stress show increased sedation to alcohol compared to low cortisol responders: An alcohol dose-response study. AB - AIMS: The present study was designed to examine the relationship between high and low cortisol response to an acute stressful situation and the subjective effects after different doses of alcohol, in healthy social drinkers. METHOD: Sixty-four subjects (32 men and 32 women) participated in one laboratory session. They performed a modified version of the Trier Social Stress Test (TSST) immediately before consumption of either placebo or alcohol (0.2, 0.4 or 0.8 g/kg). Subjects in each dose group were then divided into high (HCR; n=32) or low (LCR; n=32) cortisol responders. Primary dependent measures were self-report questionnaires of mood. RESULTS: The HCR reported increased ratings on Sedation on the Biphasic Alcohol Effects Scale (BAES) with increased dose in comparison with the LCR. This increase in sedation also correlated to the increase in cortisol levels. CONCLUSION: We conclude that a high cortisol response to stress modulates the subjective response to alcohol, dose-dependently. HCR subjects experience increased sedative effects of alcohol after consumption of higher doses of alcohol following stress compared to LCR subjects. PMID- 26892759 TI - Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-alpha, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration. AB - Inflammation plays a role in the pathophysiology of depression. The purpose of this study is to examine whether the selective serotonin reuptake inhibitor (SSRI) escitalopram, its inactive enantiomer R-citalopram, and selective noradrenaline reuptake inhibitor (NRI) reboxetine, show anti-inflammatory and antidepressant effects in an inflammation-induced model of depression. Pretreatment with escitalopram (1, 3, or 10mg/kg, i.p.) markedly blocked an increase in the serum levels of pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), after a single administration of lipopolysaccharide (LPS; 0.5mg/kg). Furthermore, escitalopram (3 or 10mg/kg) significantly increased the serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) by a single administration of LPS. In contrast, pretreatment with R-citalopram (10mg/kg, i.p.) or reboxetine (10mg/kg, i.p.) did not affect the alterations in serum levels of TNF-alpha and IL-10 after LPS administration. Co-administration of reboxetine with escitalopram did not show anti-inflammatory effects. Pretreatment with escitalopram (10mg/kg) significantly attenuated LPS-induced increase of the immobility time in the tail-suspension test (TST) and forced swimming test (FST). In contrast, pretreatment with R-citalopram (10mg/kg), or reboxetine (10mg/kg) did not alter LPS-induced increase of immobility time of TST and FST. Interestingly, co-administration of reboxetine with escitalopram did not show antidepressant effect in this model. These findings suggest that escitalopram, but not R-citalopram and reboxetine, has anti-inflammatory and antidepressant effects in LPS-treated model of depression, and that reboxetine can antagonize the effects of escitalopram in the inflammation model. Therefore, it is likely that serotonergic system plays a key role in the pathophysiology of inflammation induced depression. PMID- 26892761 TI - Agranulocytosis in a Pediatric Patient Treated With Ceftaroline. PMID- 26892762 TI - Deployable Soft Composite Structures. AB - Deployable structure composed of smart materials based actuators can reconcile its inherently conflicting requirements of low mass, good shape adaptability, and high load-bearing capability. This work describes the fabrication of deployable structures using smart soft composite actuators combining a soft matrix with variable stiffness properties and hinge-like movement through a rigid skeleton. The hinge actuator has the advantage of being simple to fabricate, inexpensive, lightweight and simple to actuate. This basic actuator can then be used to form modules capable of different types of deformations, which can then be assembled into deployable structures. The design of deployable structures is based on three principles: design of basic hinge actuators, assembly of modules and assembly of modules into large-scale deployable structures. Various deployable structures such as a segmented triangular mast, a planar structure comprised of single-loop hexagonal modules and a ring structure comprised of single-loop quadrilateral modules were designed and fabricated to verify this approach. Finally, a prototype for a deployable mirror was developed by attaching a foldable reflective membrane to the designed ring structure and its functionality was tested by using it to reflect sunlight onto to a small-scale solar panel. PMID- 26892763 TI - Mohr's method challenge. PMID- 26892760 TI - Centrally acting non-narcotic antitussives prevent hyperactivity in mice: Involvement of GIRK channels. AB - We have previously reported that centrally acting non-narcotic antitussives inhibited G protein-coupled inwardly rectifying potassium (GIRK) channel activated currents, and that the antitussives had multiple pharmacological actions on various models of intractable brain diseases in rodents. In this study, the question of whether these antitussives inhibit drug-induced hyperactivity in mice was investigated. Antitussives, such as cloperastine and tipepidine, at cough suppressant doses, inhibited an increase in ambulation of mice neonatally treated with 6-hydroxydopamine. In addition, all antitussives studied inhibited an increase in methamphetamine-induced hyperactivity in mice. Methylphenidate, which is used for treatment of ADHD, inhibited 6-hydroxydopamine lesion-induced, but not methamphetamine-induced, hyperactivity in mice. By the rota-rod test, the drugs had little effect on motor coordination of the hyperactive mice. Significant correlation was found between the ameliorating effects of antitussives on methamphetamine-induced hyperactivity and their inhibitory actions on GIRK channel currents (coefficient factor, 0.998). Furthermore, tertiapin, a GIRK channel blocker, prevented an increase in methamphetamine-induced hyperactivity of mice. These results demonstrated that antitussive drugs (cloperastine, tipepidine and caramiphen) possessing inhibitory action on GIRK channels inhibit drug-induced hyperactivity in mice, suggesting that such antitussives may potentially be therapeutic for patients with ADHD. PMID- 26892764 TI - Solution to doubling spectroscopy challenge. PMID- 26892765 TI - The Impact of Metastatic Lymph Nodes on Risk Stratification in Differentiated Thyroid Cancer: Have We Reached a Higher Level of Understanding? AB - BACKGROUND: The revised American Thyroid Association (ATA) management guidelines for differentiated thyroid cancer emphasize a variety of clinicopathologic features of metastatic lymph nodes in determining the risk of recurrence. The mere presence of a positive node is not sufficient to confer reliable prognostic significance. The number and size of lymph nodes, as well as the presence of extranodal extension (ENE), impact risk stratification. Moreover, the presence of clinically evident lymph nodes is important for determining risk of recurrence. A patient's place on the risk spectrum has ramifications for the management of differentiated thyroid cancer. However, there are inherent inconsistencies in the identification and characterization of metastatic lymph nodes. Moreover, the significance of ENE must be clarified. SUMMARY: There are many obstacles to the consistent reporting of metastatic lymph nodes. What constitutes a "clinically evident" lymph node has not been well defined, lacks precision, and varies depending on clinical context, as well as the experience of the surgeon and the ultrasonographer. The number of lymph nodes sampled by surgeons and reported by pathologists may vary from institution to institution. The literature on ENE has been limited by the fact that the definition of ENE has not been standardized. Nevertheless, 17/19 manuscripts reviewed herein suggest that ENE confers a worse prognosis. The ATA risk stratification for metastatic lymph nodes published in the 2015 guidelines combines clinicopathological features that are variably identified and reported across institutions. This review brings into question the significance of the number of nodes with ENE, a factor that is used as an important stratifying variable in the latest guidelines. CONCLUSIONS: Metastatic lymph nodes do not all carry the same prognostic significance, but a risk assignment based on the ATA guidelines is limited by a lack of standardization in clinical and pathologic definitions, lymph node sampling, and reporting. This study reviews the limitations of prior studies on ENE and concludes that the body of the evidence reported in those studies suggests that ENE increases the risk of recurrence. The impact of ENE in lymph nodes in thyroid cancer risk stratification should be reconsidered. PMID- 26892767 TI - The experiences of protective isolation in patients undergoing bone marrow or haematopoietic stem cell transplantation: systematic review and metasynthesis. AB - Protective isolation is aimed at preventing infection in neutropenic patients, but it is implemented inconsistently across centres and is supported by recommendations with poor evidence. This review and metasynthesis explored the experiences and the psychological implications of protective isolation in patients with haematological malignancies undergoing bone marrow (BMT) or haematopoietic stem cell transplantation (HSCT). A systematic search of multiple databases for qualitative studies exploring BMT or HSCT patients' experiences of protective isolation was completed. The metasynthesis followed the meta aggregative method from the Joanna Briggs Institute, with four procedural steps: (1) comprehensive search, (2) quality appraisal, (3) extraction of relevant findings and (4) synthesis of the identified findings. Twenty-six findings were extracted from 11 articles included in the review. The synthesising process yielded seven categories, aggregated into three synthesised findings: (1) isolation is a source of suffering, (2) isolation can lead to relating with oneself and (3) the person does not close the door to the outside world. This metasynthesis sheds light on patients' suffering from being isolated, and the possibility of overcoming this suffering thanks to relationships that patients have with themselves and with the external world. Healthcare providers should reconsider this practise in order to avoid unnecessary patient suffering. PMID- 26892766 TI - Patients with celiac disease may have normal weight or may even be overweight. AB - BACKGROUND: It is believed that patients with celiac disease (CeD) are likely to be underweight. Data from west suggest that 8% to 40% of them can be overweight or obese. We reviewed data on body mass index (BMI) of our patients with CeD and derived the correlations between BMI and other disease characteristics. METHODS: We retrospectively studied case records of 210 adolescent and adult patients with CeD at the Celiac Disease Clinic. We classified BMI as underweight, normal weight, overweight, and obese based on the Consensus Statement for Diagnosis of Obesity, Abdominal Obesity and the Metabolic Syndrome for Asian Indians for those with age >18 years and revised Indian Association of Pediatrics BMI-for-age charts for those between 12 and 18 years. RESULTS: Of 210 patients, 76 (36.2%) were underweight, 115 (54.8%) were normal weight, 13 (6.2%) were overweight, and 6 (2.9%) were obese. There was no difference in the proportion of underweight between male and female patients with CeD. The mean age of underweight patients was similar to those having normal or overweight. There was no difference in the mean duration of symptoms; frequencies of diarrhea, anorexia, and weakness; anemia; titer of anti-tissue transglutaminase antibody; and severity of villous atrophy in those with underweight or normal weight or overweight. CONCLUSIONS: In our practice, only one third of patients with CeD had low BMI. A diagnosis of CeD should not be excluded if patient has normal or high BMI. PMID- 26892769 TI - Many faces of dogmatism: Prejudice as a way of protecting certainty against value violators among dogmatic believers and atheists. AB - In this article, we suggest that dogmatic beliefs, manifested as strong beliefs that there is no God (i.e., dogmatic atheism) as well as strong beliefs in God (i.e., religious orthodoxy), can serve as a cognitive response to uncertainty. Moreover, we claim that people who dogmatically do not believe in religion and those who dogmatically believe in religion are equally prone to intolerance and prejudice towards groups that violate their important values. That is because prejudice towards these groups may be an efficient strategy to protect the certainty that strong beliefs provide. We tested these assumptions in two studies. In Study 1 and Study 2, we demonstrated that dogmatic beliefs mediate the relationship between intolerance to uncertainty and both, religious orthodoxy and dogmatic atheism. In addition, in Study 2 we showed that both the religiously orthodox and dogmatic atheists become prejudiced towards groups that violate their values and that these effects are especially strong under experimentally induced uncertainty. In this study, we focused on atheists and homosexuals as groups that pose a threat to Christian's religious worldviews, and Catholics and pro-life supporters as groups that pose a threat to the values of atheists. The results are discussed in relation to past research on dogmatism and religion, as well as with reference to what this means for the study of prejudice. PMID- 26892768 TI - Can arbuscular mycorrhizal fungi reduce Cd uptake and alleviate Cd toxicity of Lonicera japonica grown in Cd-added soils? AB - A greenhouse pot experiment was conducted to study the impact of arbuscular mycorrhizal fungi--Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the growth, Cd uptake, antioxidant indices [glutathione reductase (GR), ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), ascorbate (ASA), glutathione (GSH) and malonaldehyde (MDA)] and phytochelatins (PCs) production of Lonicera japonica in Cd-amended soils. Gv and Ri significantly increased P acquisition, biomass of shoots and roots at all Cd treatments. Gv significantly decreased Cd concentrations in shoots and roots, and Ri also obviously reduced Cd concentrations in shoots but increased Cd concentrations in roots. Meanwhile, activities of CAT, APX and GR, and contents of ASA and PCs were remarkably higher in Gv/Ri-inoculated plants than those of uninoculated plants, but lower MDA and GSH contents in Gv/Ri-inoculated plants were found. In conclusion, Gv and Ri symbiosis alleviated Cd toxicity of L. japonica through the decline of shoot Cd concentrations and the improvement of P nutrition, PCs content and activities of GR, CAT, APX in inoculated plants, and then improved plant growth. The decrease of shoot Cd concentrations in L. japonica inoculated with Gv/Ri would provide a clue for safe production of this plant from Cd-contaminated soils. PMID- 26892772 TI - Erratum to: Route and survey processing of topographical memory during navigation. PMID- 26892771 TI - The 10 largest public and philanthropic funders of health research in the world: what they fund and how they distribute their funds. AB - BACKGROUND: Little is known about who the main public and philanthropic funders of health research are globally, what they fund and how they decide what gets funded. This study aims to identify the 10 largest public and philanthropic health research funding organizations in the world, to report on what they fund, and on how they distribute their funds. METHODS: The world's key health research funding organizations were identified through a search strategy aimed at identifying different types of funding organizations. Organizations were ranked by their reported total annual health research expenditures. For the 10 largest funding organizations, data were collected on (1) funding amounts allocated towards 20 health areas, and (2) schemes employed for distributing funding (intramural/extramural, project/'people'/organizational and targeted/untargeted funding). Data collection consisted of a review of reports and websites and interviews with representatives of funding organizations. Data collection was challenging; data were often not reported or reported using different classification systems. RESULTS: Overall, 55 key health research funding organizations were identified. The 10 largest funding organizations together funded research for $37.1 billion, constituting 40% of all public and philanthropic health research spending globally. The largest funder was the United States National Institutes of Health ($26.1 billion), followed by the European Commission ($3.7 billion), and the United Kingdom Medical Research Council ($1.3 billion). The largest philanthropic funder was the Wellcome Trust ($909.1 million), the largest funder of health research through official development assistance was USAID ($186.4 million), and the largest multilateral funder was the World Health Organization ($135.0 million). Funding distribution mechanisms and funding patterns varied substantially between the 10 largest funders. CONCLUSIONS: There is a need for increased transparency about who the main funders of health research are globally, what they fund and how they decide on what gets funded, and for improving the evidence base for various funding models. Data on organizations' funding patterns and funding distribution mechanisms are often not available, and when they are, they are reported using different classification systems. To start increasing transparency in health research funding, we have established www.healthresearchfunders.org that lists health research funding organizations worldwide and their health research expenditures. PMID- 26892770 TI - DNA origami based Au-Ag-core-shell nanoparticle dimers with single-molecule SERS sensitivity. AB - DNA origami nanostructures are a versatile tool to arrange metal nanostructures and other chemical entities with nanometer precision. In this way gold nanoparticle dimers with defined distance can be constructed, which can be exploited as novel substrates for surface enhanced Raman scattering (SERS). We have optimized the size, composition and arrangement of Au/Ag nanoparticles to create intense SERS hot spots, with Raman enhancement up to 10(10), which is sufficient to detect single molecules by Raman scattering. This is demonstrated using single dye molecules (TAMRA and Cy3) placed into the center of the nanoparticle dimers. In conjunction with the DNA origami nanostructures novel SERS substrates are created, which can in the future be applied to the SERS analysis of more complex biomolecular targets, whose position and conformation within the SERS hot spot can be precisely controlled. PMID- 26892773 TI - An interpolated activity during the knowledge-of-results delay interval eliminates the learning advantages of self-controlled feedback schedules. AB - The learning advantages of self-controlled knowledge-of-results (KR) schedules compared to yoked schedules have been linked to the optimization of the informational value of the KR received for the enhancement of one's error detection capabilities. This suggests that information-processing activities that occur after motor execution, but prior to receiving KR (i.e., the KR-delay interval) may underlie self-controlled KR learning advantages. The present experiment investigated whether self-controlled KR learning benefits would be eliminated if an interpolated activity was performed during the KR-delay interval. Participants practiced a waveform matching task that required two rapid elbow extension-flexion reversals in one of four groups using a factorial combination of choice (self-controlled, yoked) and KR-delay interval (empty, interpolated). The waveform had specific spatial and temporal constraints, and an overall movement time goal. The results indicated that the self-controlled + empty group had superior retention and transfer scores compared to all other groups. Moreover, the self-controlled + interpolated and yoked + interpolated groups did not differ significantly in retention and transfer; thus, the interpolated activity eliminated the typically found learning benefits of self controlled KR. No significant differences were found between the two yoked groups. We suggest the interpolated activity interfered with information processing activities specific to self-controlled KR conditions that occur during the KR-delay interval and that these activities are vital for reaping the associated learning benefits. These findings add to the growing evidence that challenge the motivational account of self-controlled KR learning advantages and instead highlights informational factors associated with the KR-delay interval as an important variable for motor learning under self-controlled KR schedules. PMID- 26892774 TI - The natural history of latent rheumatic heart disease in a 5 year follow-up study: a prospective observational study. AB - BACKGROUND: Latent rheumatic heart disease (RHD) occurs in asymptomatic individuals with echocardiographic evidence of RHD and no history of acute rheumatic fever. The natural history of latent RHD is unclear but has important clinical and economic implications about whether these children should receive penicillin prophylaxis or not. We performed a 5-year prospective study of this question. METHODS: In August 2013 through September 2014, we conducted a follow up study of latent RHD among school pupils using the World Heart Federation (WHF) echocardiographic criteria. Contingency tables were used to assess progression, persistence or regression of latent RHD. RESULTS: Forty two borderline and 13 definite cases of RHD (n 55) were identified, 44 (80%; mean age 13.8 +/- 4.0 years; 29 (65.9%) female) of whom were available for echocardiographic examination at a median follow-up of 60.8 months (interquartile range 51.3-63.5). Over the follow-up period, half the participants (n = 23; 52.3%) improved to normal or better WHF category (regressors), a third (n = 14, 31.8%) remained in the same category (persistors), while seven others (15.9%) progressed from borderline to definite RHD (progressors). In total, 21 subjects (47.7%) reverted to a normal status, nine (20.4%) either improved from definite to borderline or remained in the borderline category, and 14 (31.8%) either remained definite or progressed from borderline to a definite status. Two cases (20%) progressed to symptomatic disease. CONCLUSIONS: Latent RHD has a variable natural history that ranges from regression to normal in nearly half of cases, to persistence, progression or development of symptoms in the remainder of subjects. PMID- 26892775 TI - A block mixture model to map eQTLs for gene clustering and networking. AB - To study how genes function in a cellular and physiological process, a general procedure is to classify gene expression profiles into categories based on their similarity and reconstruct a regulatory network for functional elements. However, this procedure has not been implemented with the genetic mechanisms that underlie the organization of gene clusters and networks, despite much effort made to map expression quantitative trait loci (eQTLs) that affect the expression of individual genes. Here we address this issue by developing a computational approach that integrates gene clustering and network reconstruction with genetic mapping into a unifying framework. The approach can not only identify specific eQTLs that control how genes are clustered and organized toward biological functions, but also enable the investigation of the biological mechanisms that individual eQTLs perturb in a signaling pathway. We applied the new approach to characterize the effects of eQTLs on the structure and organization of gene clusters in Caenorhabditis elegans. This study provides the first characterization, to our knowledge, of the effects of genetic variants on the regulatory network of gene expression. The approach developed can also facilitate the genetic dissection of other dynamic processes, including development, physiology and disease progression in any organisms. PMID- 26892776 TI - Trends and patterns of antibiotic consumption in Shanghai municipality, China: a 6 year surveillance with sales records, 2009-14. AB - OBJECTIVES: The objective of this study was to identify the trends and patterns of total antibiotic use in Shanghai from 2009 to 2014. METHODS: Sales records were collected from a minimum of 160 hospitals and 241 primary healthcare settings and used as a proxy for consumption. Antibiotic sales expressed in DDD per 1000 inhabitants per day (DID) were calculated. We compared patterns of antibiotic use in the Shanghai municipality, populated by 24 million inhabitants, with European countries using indicators from the European Surveillance of Antimicrobial Consumption (ESAC). RESULTS: Total antibiotic use was highest at 25.9 DID in 2010, fell to 17.8 DID in 2012 and remained stable thereafter. The majority of this reduction occurred over 6 months in 2011. In 2014, two-thirds of the antibiotic sales were to hospitals (serving both inpatients and outpatients) and one-third to primary healthcare institutions. Cephalosporins accounted for 50.2% of total DID, followed by macrolides (18.2%), quinolones (16.0%) and penicillins (7.3%). A fifth of all antibiotics were used in parenteral form. CONCLUSIONS: We have successfully used aggregated sales data to monitor antibiotic usage across a large urban population over a 6 year period. A rapid, substantial and sustained reduction in antibiotic usage across the entire health system occurred. This coincided with several interventions across hierarchies in the health sector, including a national campaign. The patterns of antibiotic use indicate persistent preferences for cephalosporins, macrolides, quinolones and parenteral preparations. Further efforts are needed to investigate and improve the quality of antibiotic use. PMID- 26892778 TI - Chromobacterium spp. harbour Ambler class A beta-lactamases showing high identity with KPC. AB - OBJECTIVES: The origin of KPC is unknown. The aim of this study was to detect progenitors of KPC in silico and to functionally verify their beta-lactam hydrolysis activity. METHODS: The sequence of KPC-2 was used to mine the NCBI protein sequence database. The best non-KPC hits were analysed by amino acid (aa) alignment and phylogenetic tree construction. Genes encoding KPC-2 homologues were expressed in Escherichia coli. The carbapenemase activities of the recombinant strains were characterized by the CarbaNP test and UV spectrophotometry and MICs of selected beta-lactams were determined. RESULTS: Genes encoding the closest KPC-2 homologues were identified on the chromosome of Chromobacterium piscinae strain ND17 (CRP-1, 76% aa identity), Chromobacterium sp. C-61 (CRS-1, 70% aa identity) and Chromobacterium haemolyticum DSM19808 (CRH 1, 69% aa identity). All three Chromobacterium beta-lactamases were phylogenetically more related to KPC than to other Ambler class A beta lactamases. The 27 bp region preceding the start codon of blaCRP-1 displayed high nucleotide identity to the corresponding region upstream from blaKPC (74%). Heterologous expression of blaCRP-1 and to a lesser extent of blaCRH-1 in E. coli significantly increased the MICs of meropenem and most cephalosporins. The CarbaNP test was positive for both recombinant strains, but spectrophotometric analysis confirmed higher carbapenemase activity for CRP-1-producing clones. CONCLUSIONS: The recovery of three class A beta-lactamases with up to 76% aa identity to KPC from distinct Chromobacterium species is highly indicative of the role played by this genus in the evolution of KPC. PMID- 26892779 TI - Non-susceptibility of Escherichia coli, Klebsiella spp., Pseudomonas spp., Streptococcus pneumoniae and Staphylococcus aureus in the UK: temporal trends in England, Northern Ireland, Scotland and Wales. AB - OBJECTIVES: To monitor and compare trends in the non-susceptibility of bloodstream isolates of pathogens to key antibiotics in the constituent countries of the UK between 2010 and 2014. METHODS: Routinely generated antibiotic susceptibility test results for bloodstream isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas spp., Streptococcus pneumoniae and Staphylococcus aureus were collected from hospital microbiology laboratories in each country. RESULTS: With the exception of a decrease in the proportion of S. aureus that were MRSA, non-susceptibility to key antibiotics among the pathogens studied remained largely unchanged over the 5 year study period, with any increases in non-susceptibility being small. Although some intercountry variation in the proportions of non-susceptible isolates was seen, apart from MRSA, the differences were generally small (<5%) and fluctuated from year to year, with no country showing consistently higher or lower rates of resistance. CONCLUSIONS: Collaboration between the constituent countries of the UK allows an integrated approach to nationwide surveillance of antibiotic resistance. PMID- 26892777 TI - Pharmacogenetics of unboosted atazanavir in HIV-infected individuals in resource limited settings: a sub-study of the AIDS Clinical Trials Group (ACTG) PEARLS study (NWCS 342). AB - OBJECTIVES: The multinational PEARLS (ACTG A5175) study, conducted mainly in resource-limited settings, identified an increased treatment failure rate among HIV-infected individuals randomized to once-daily unboosted atazanavir, didanosine-EC, and emtricitabine compared with efavirenz-based regimens. We evaluated associations between selected human genetic polymorphisms and atazanavir pharmacokinetics in PEARLS. METHODS: Polymorphisms in CYP3A5, ABCB1, SLCO1B1 and NR1I2 were genotyped in PEARLS participants randomized to atazanavir plus didanosine-EC plus emtricitabine in Peru, South Africa and the USA, who also consented to genetic analysis. Non-linear mixed-effects population pharmacokinetic modelling was used to predict atazanavir oral clearance (CL/F) and concentration at 24 h (C24). Atazanavir mono-oxidation metabolites M1 and M2 were quantified from the same single-point plasma sample used to quantify the parent drug. Data were log10 transformed for statistical analysis using unpaired t-tests and one-way ANOVA and are presented as geometric mean (95% CI). RESULTS: Eighty-four HIV-infected participants were genotyped, including 44 Black Africans or African Americans and 28 women. Median age was 34 years. We identified 56 CYP3A5 expressers and 28 non-expressers. Atazanavir CL/F and C24 did not differ between CYP3A5 expressers and non-expressers: 13.2 (12.1-14.4) versus 12.7 L/h (11.7-13.9), P = 0.61, and 75.3 (46.1-123.0) versus 130.9 ng/mL (86.9-197.2), P = 0.14, respectively. M1/atazanavir and M2/atazanavir ratios were higher in expressers than in non-expressers: 0.0083 (0.0074-0.0094) versus 0.0063 (0.0053 0.0075), P = 0.008, and 0.0065 (0.0057-0.0073) versus 0.0050 (0.0042-0.0061), P = 0.02, respectively. CONCLUSIONS: Expression of CYP3A5 appears to be associated with increased M1 and M2 atazanavir metabolite formation, without significantly affecting parent compound pharmacokinetics. PMID- 26892780 TI - Understanding the dispensary workflow at the Birmingham Free Clinic: a proposed framework for an informatics intervention. AB - BACKGROUND: The Birmingham Free Clinic (BFC) in Pittsburgh, Pennsylvania, USA is a free, walk-in clinic that serves medically uninsured populations through the use of volunteer health care providers and an on-site medication dispensary. The introduction of an electronic medical record (EMR) has improved several aspects of clinic workflow. However, pharmacists' tasks involving medication management and dispensing have become more challenging since EMR implementation due to its inability to support workflows between the medical and pharmaceutical services. To inform the design of a systematic intervention, we conducted a needs assessment study to identify workflow challenges and process inefficiencies in the dispensary. METHODS: We used contextual inquiry to document the dispensary workflow and facilitate identification of critical aspects of intervention design specific to the user. Pharmacists were observed according to contextual inquiry guidelines. Graphical models were produced to aid data and process visualization. We created a list of themes describing workflow challenges and asked the pharmacists to rank them in order of significance to narrow the scope of intervention design. RESULTS: Three pharmacists were observed at the BFC. Observer notes were documented and analyzed to produce 13 themes outlining the primary challenges pharmacists encounter during dispensation at the BFC. The dispensary workflow is labor intensive, redundant, and inefficient when integrated with the clinical service. Observations identified inefficiencies that may benefit from the introduction of informatics interventions including: medication labeling, insufficient process notification, triple documentation, and inventory control. CONCLUSIONS: We propose a system for Prescription Management and General Inventory Control (RxMAGIC). RxMAGIC is a framework designed to mitigate workflow challenges and improve the processes of medication management and inventory control. While RxMAGIC is described in the context of the BFC dispensary, we believe it will be generalizable to pharmacies in other low resource settings, both domestically and internationally. PMID- 26892782 TI - RNA fragments mimicking tRNA analogs interact with cytochrome c. AB - In times, when drug seeking assays focus on the natural molecular triggers and their analogs, a deeper insight into molecular mechanisms governing the initial step of intrinsic apoptosis (cytochrome c release) is essential to suppress the immortality of pathologically changed cells. In this study, we examined RNA molecules mimicking mitochondrial tRNAs interacting with cytochrome c and possibly affecting its cellular function. tRNA analogs were designed and synthesized prior to the conformational analysis and gel assays clearly stating the nucleic acid-protein complex formation. The circular dichroism spectroscopic (CD) and microscale thermophoresis examination revealed the structural and conformational differences between four tRNA analogs in their interactions with cytochrome c. Obtained CD spectra and gel studies resulted in the complex ratio estimation and conclusion that not only the complex formation may be preferential towards specific tRNAs present in the cell, but nucleobase modifications are not essential for such interaction. PMID- 26892783 TI - Novel identification of Factor XI deficiency in Indian Sahiwal (Bos indicus) cattle. AB - Factor-XI deficiency (FXID) is inherited as autosomal lethal recessive disorder of carrier Holstein-Friesian bulls. A 76 base pair segment insertion into exon 12 in Factor-XI gene causes FXID in cattle. Keeping this in view the present study was conducted to screen breeding bulls of both indigenous and exotic breeds for mutation in Factor-XI gene and to find out the frequency of FXID carrier animals in breeding bulls. A total of 120 bulls of different age group maintained at Frozen Semen Bull Station, India were randomly selected from different cattle breeds to screen presence of FXID syndrome in breeding sires. Genomic DNA was isolated from blood of the selected bulls. PCR parameters were standardized to obtain 244 and 320 bp amplicons. The results showed that 2 Sahiwal bulls out of 120 animals were carrier for FXID. Amplicons of the carrier animals were sequenced and annoted, which confirms a 76 bp insertion in the exon 12. Bleeding and clotting time showed considerable discrepancy in the carrier animals as compared to the normal animals. The findings of relative mRNA expression of Factor XI transcript revealed identical tendency in the carrier. The frequency of carrier animals and mutant allele was 2.5 % and 0.025 respectively. This study recommends for screening of breeding at AI bull centers in the country for FXID. The study also stands a merit for identification of FXID carrier in Bos indicus for the first time. PMID- 26892786 TI - Asymmetry of Facial Mimicry and Emotion Perception in Patients With Unilateral Facial Paralysis. AB - IMPORTANCE: The ability of patients with unilateral facial paralysis to recognize and appropriately judge facial expressions remains underexplored. OBJECTIVE: To test the effects of unilateral facial paralysis on the recognition of and judgments about facial expressions of emotion and to evaluate the asymmetry of facial mimicry. DESIGN, SETTING, AND PARTICIPANTS: Patients with left or right unilateral facial paralysis at a university facial plastic surgery unit completed 2 computer tasks involving video facial expression recognition. Side of facial paralysis was used as a between-participant factor. Facial function and symmetry were verified electronically with the eFACE facial function scale. EXPOSURES: Across 2 tasks, short videos were shown on which facial expressions of happiness and anger unfolded earlier on one side of the face or morphed into each other. Patients indicated the moment or side of change between facial expressions and judged their authenticity. MAIN OUTCOMES AND MEASURES: Type, time, and accuracy of responses on a keyboard were analyzed. RESULTS: A total of 57 participants (36 women and 21 men) aged 20 to 76 years (mean age, 50.2 years) and with mild left or right unilateral facial paralysis were included in the study. Patients with right facial paralysis were faster (by about 150 milliseconds) and more accurate (mean number of errors, 1.9 vs 2.5) to detect expression onsets on the left side of the stimulus face, suggesting anatomical asymmetry of facial mimicry. Patients with left paralysis, however, showed more anomalous responses, which partly differed by emotion. CONCLUSIONS AND RELEVANCE: The findings favor the hypothesis of an anatomical asymmetry of facial mimicry and suggest that patients with a left hemiparalysis could be more at risk of developing a cluster of disabilities and psychological conditions including emotion-recognition impairments. LEVEL OF EVIDENCE: 3. PMID- 26892785 TI - Binding interface change and cryptic variation in the evolution of protein protein interactions. AB - BACKGROUND: Physical interactions between proteins are essential for almost all biological functions and systems. To understand the evolution of function it is therefore important to understand the evolution of molecular interactions. Of key importance is the evolution of binding specificity, the set of interactions made by a protein, since change in specificity can lead to "rewiring" of interaction networks. Unfortunately, the interfaces through which proteins interact are complex, typically containing many amino-acid residues that collectively must contribute to binding specificity as well as binding affinity, structural integrity of the interface and solubility in the unbound state. RESULTS: In order to study the relationship between interface composition and binding specificity, we make use of paralogous pairs of yeast proteins. Immediately after duplication these paralogues will have identical sequences and protein products that make an identical set of interactions. As the sequences diverge, we can correlate amino acid change in the interface with any change in the specificity of binding. We show that change in interface regions correlates only weakly with change in specificity, and many variants in interfaces are functionally equivalent. We show that many of the residue replacements within interfaces are silent with respect to their contribution to binding specificity. CONCLUSIONS: We conclude that such functionally-equivalent change has the potential to contribute to evolutionary plasticity in interfaces by creating cryptic variation, which in turn may provide the raw material for functional innovation and coevolution. PMID- 26892781 TI - The renewed battle against RAS-mutant cancers. AB - The RAS genes encode for members of a large superfamily of guanosine-5' triphosphate (GTP)-binding proteins that control diverse intracellular signaling pathways to promote cell proliferation. Somatic mutations in the RAS oncogenes are the most common activating lesions found in human cancers. These mutations invariably result in the gain-of-function of RAS by impairing GTP hydrolysis and are frequently associated with poor responses to standard cancer therapies. In this review, we summarize key findings of past and present landmark studies that have deepened our understanding of the RAS biology in the context of oncogenesis. We also discuss how emerging areas of research could further bolster a renewed global effort to target the largely undruggable oncogenic RAS and/or its activated downstream effector signaling cascades to achieve better treatment outcomes for RAS-mutant cancer patients. PMID- 26892787 TI - Effects of urban land-use on largescale stonerollers in the Mobile River Basin, Birmingham, AL. AB - During the spring and fall of 2001 and the spring of 2002 a study was conducted to evaluate the health of the largescale stoneroller (Campostoma oligolepis) populations in streams along an urban land-use gradient. Sites were selected from a pool of naturally similar sub-basins (eco-region, basin size, and geology) of the Mobile River basin (MRB), using an index of urban intensity derived from infrastructure, socioeconomic, and land-use data. This urban land-use gradient (ULUG) is a multimetric indicator of urban intensity, ranging from 0 (background) to 100 (intense urbanization). Campostoma sp. have been used previously as indicators of stream health and are common species found in all sites within the MRB. Endpoints used to determine the effects of urban land-use on the largescale stoneroller included total glutathione, histology, hepatic apoptosis, condition factor and external lesions. Liver glutathione levels were positively associated with increasing urban land-use (r(2) = 0.94). Histopathological examination determined that some abnormalities and lesions were correlated with the ULUG and generally increased in prevalence or severity with increasing urbanization. Liver macrophage aggregates were positively correlated to the ULUG. The occurrence of nucleosomal ladders (indicating apoptotic cell death) did not correspond with urban intensity in a linear fashion. Apoptosis, as well as prevalence and severity of a myxozoan parasite, appeared to have a hormetic dose-response relationship. The majority of the biomarkers suggested fish health was compromised in areas where the ULUG >= 36. PMID- 26892784 TI - Event-related potentials elicited by the Deutsch "high-low" word illusion in the patients with first-episode schizophrenia with auditory hallucinations. AB - BACKGROUND: The exact cerebral structural and functional mechanisms under the auditory verbal hallucinations (AVHs) in schizophrenia are still unclear. The Deutsch "high-low" word illusion might trigger attentional responses mimicking those under AVHs. METHODS: We therefore have invited 16 patients with first episode, paranoid schizophrenia, and 16 age- and gender-matched healthy volunteers to undergo the "oddball" event-related potentials elicited by the illusion. The clinical characteristics of patients were measured with the positive and negative symptom scale. RESULTS: Besides the longer reaction time to the illusion, the standard P2 latency was shortened, the N2 latency was prolonged, and both N1 and P3 amplitudes were reduced in patients. The P3 source analyses showed the activated bilateral temporal lobes, parietal lobe and cingulate cortex in both groups, left inferior temporal gyrus in controls, and left postcentral gyrus in schizophrenia. Moreover, the N1 amplitude was positively correlated with the paranoid score in patients. CONCLUSIONS: Our results were in line with previous neurophysiological and neuroimaging reports of hallucination or auditory processing in schizophrenia, and illustrated a whole process of cerebral information processing from N1 to P3, indicating this illusion had triggered a dynamic cerebral response similar to that of the AVHs had engaged. PMID- 26892788 TI - Multibiomarker response in the earthworm Eisenia fetida as tool for assessing multi-walled carbon nanotube ecotoxicity. AB - Carbon nanotubes have received a great attention in the last years thanks to their remarkable structural, electrical, and chemical properties. Nowadays carbon nanotubes are increasingly found in terrestrial and aquatic environment and potential harmful impacts of these nanoparticles on humans and wildlife are attracting increasing research and public attention. The effects of carbon nanotubes on aquatic organisms have been explored by several authors, but comparatively the information available on the impact of these particles on soil organisms is much less. Earthworms have traditionally been considered to be convenient indicators of land use impact and soil fertility. The aim of this work was to study the integrated response of a suite of biomarkers covering molecular to whole organism endpoints for the assessment of multi-walled carbon nanotube (MWCNTs) effects on earthworms (Eisenia fetida) exposed to spiked soil. Results showed that cellular and biochemical responses, such as immune cells morphometric alterations and lysosomal membrane destabilization, acetylcholinesterase inhibition and metallothionein tissue concentration changes, showed high sensitivity to MWCNTs exposure. They can improve our understanding and ability to predict chronic toxicity outcomes of MWCNTs exposure such as reproductive alterations. In this context although more investigation is needed to understand the mechanistic pathway relating the biochemical and cellular biomarker analyzed to reproductive alterations, the obtained results give an early contribution to the future development of an adverse outcomes pathways for MWCNTs exposure. PMID- 26892789 TI - How often are interventions in cluster-randomised controlled trials of complex interventions in general practices effective and reasons for potential shortcomings? Protocol and results of a feasibility project for a systematic review. AB - INTRODUCTION: Most studies conducted at general practices investigate complex interventions and increasingly use cluster-randomised controlled trail (c-RCT) designs to do so. Our primary objective is to evaluate how frequently complex interventions are shown to be more, equally or less effective than routine care in c-RCTs with a superior design. The secondary aim is to discover whether the quality of a c-RCT determines the likelihood of the complex intervention being effective. METHODS AND ANALYSIS: All c-RCTs of any design that have a patient relevant primary outcome and with a duration of at least 1 year will be included. The search will be performed in three electronic databases (MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews (CDSR)). The screening process, data collection, quality assessment and statistical data analyses (if suitably similar and of adequate quality) will be performed in accordance with requirements of the Cochrane Handbook for Systematic Reviews of Interventions. A feasibility project was carried out that was restricted to a search in MEDLINE and the CCTR for c RCTs published in 1 of the 8 journals that are most relevant to general practice. The process from trial selection to data collection, assessment and results presentation was piloted. Of the 512 abstracts identified during the feasibility search, 21 studies examined complex interventions in a general practice setting. Extrapolating the preliminary search to include all relevant c-RCTs in three databases, about 5000 abstracts and 150 primary studies are expected to be identified in the main study. 14 studies included in the feasibility project (67%) did not show a positive effect on a primary patient-relevant end point. ETHICS AND DISSEMINATION: Ethical approval is not being sought for this review. Findings will be disseminated via peer-reviewed journals that frequently publish articles on the results of c-RCTs and through presentations at international conferences. TRIAL REGISTRATION NUMBER: PROSPERO CRD201400923. PMID- 26892790 TI - Is herpes zoster an additional complication in old age alongside comorbidity and multiple medications? Results of the post hoc analysis of the 12-month longitudinal prospective observational ARIZONA cohort study. AB - OBJECTIVES: To examine the burden of comorbidity, polypharmacy and herpes zoster (HZ), an infectious disease, and its main complication post-herpetic neuralgia (PHN) in young (50-70 years of age: 70-) and old (>= 70 years of age: 70+) patients. DESIGN: Post hoc analysis of the results of the 12-month longitudinal prospective multicentre observational ARIZONA cohort study. SETTINGS AND PARTICIPANTS: The study took place in primary care in France from 20 November 2006 to 12 September 2008. Overall, 644 general practitioners (GPs) collected data from 1358 patients aged 50 years or more with acute eruptive HZ. OUTCOME MEASURES: Presence of HZ-related pain or PHN (pain persisting >3 months) was documented at day 0 and at months 3, 6, and 12. To investigate HZ and PHN burden, pain, quality of life (QoL) and mood were self-assessed using validated questionnaires (Zoster Brief Pain Inventory, 12-item Short-Form health survey and Hospital Anxiety and Depression Scale, respectively). RESULTS: As compared with younger patients, older patients more frequently presented with comorbidities, more frequently took analgesics and had poorer response on all questionnaires, indicating greater burden, at inclusion. Analgesics were more frequently prescribed to relieve acute pain or PHN in 70+ than 70- patients. Despite higher levels of medication prescription, poorer pain relief and poorer response to all questionnaires were reported in 70+ than 70- patients. CONCLUSIONS: Occurrence of HZ and progression to PHN adds extra burden on top of pharmacological treatment and impaired quality of life, especially in older patients who already have health problems to cope with in everyday life. PMID- 26892791 TI - Association between direct and indirect smoking and osteoarthritis prevalence in Koreans: a cross-sectional study. AB - OBJECTIVES: To assess the association between smoking patterns and knee and hip joint osteoarthritis (OA) prevalence in Koreans aged 50 years or older with focus on knee OA. DESIGN: Cross-sectional study using nationally representative data. SETTING: Data were collected at portable Health Examination Centres in Korea. PARTICIPANTS: Data of 9064 participants of the 5th Korean National Health and Nutrition Examination Survey (2010-2012) aged 50 years or older who received knee or hip joint X-rays out of 31,596 total surveyees were analysed. PRIMARY OUTCOME MEASURES: OA prevalence by smoking behaviour (current smoking, past smoking, indirect smoking and non-smoking). SECONDARY OUTCOME MEASURES: Estimated risk of OA by smoking amount, period, pack-years and indirect smoking exposure time to assess the association between smoking-related factors and knee OA by calculating ORs and adjusting for covariates in a complex sampling design. A multinomial logistic regression analysis and backward elimination method was used. RESULTS: OA prevalence in Koreans aged 50 years or older was 13.9%, with prevalence about 3.5 times higher in women (men 5.7%, women 20.1%). ORs for knee and hip joint OA prevalence by smoking behaviour in male indirect-smokers were lower than those in non-smokers in age and sex (OR 0.271; 95% CI 0.088 to 0.828), and selective adjustments (OR 0.314; 95% CI 0.102 to 0.966). All other analyses for smoking behaviour and total OA prevalence, and knee OA prevalence were not significantly different. Associations between smoking amount, period, pack-years and knee OA prevalence were non-significant in ever-smokers. Associations between indirect smoking exposure time and knee OA prevalence were also non-significant. CONCLUSIONS: This study found that though direct and previous smoking and OA prevalence were not associated, there was a weak relationship between indirect smoking and OA. PMID- 26892793 TI - Identification and characterization of miR-31 potential targets by RNA-seq. AB - In our previous work, miR-31 displayed differential significant expression in Apostichopus japonicus sea cucumber with skin ulcer syndrome and modulated coelomocytes ROS production by targeting p105. To identify other promising targets ofmiR-31, 4 transcriptome libraries of coelomocytes, as well as 2 control libraries, were constructed frommiR-31 mimics (31 M) or AMO-miR-31 (31I) and injected into a sea cucumber at 12 and 24 h. A total of207,977 unigenes with an average length of 363 bp were assembled, in which17,204 distinct sequences (8.27% of the unigenes) were successfully matched with annotated protein sequences. Fragments per kilobase of transcript per million fragments mapped analysis indicated that 1325 unigenes displayed up-regulated expression profiles in the 31I-12 group and were depressed in the 31M - 12 group compared with the control group. A total of 1470 unigenes showed down-regulated expressions in 31I-12 and were induced in 31 M-12. Similarly, 2079 and 2098 unigenes were detected at 24 h post-injection. Among these unigenes, 36 unigenes (depressed expression in the 31 M group and induced in the 31I group) showed consistent expression patterns at 2 examined time points and were considered promising targets of miR-31. qPCR analysis confirmed that all 4 unigenes showed opposite expression profiles to miR 31 in cultured coelomocytes. Our present work provided a fast and feasible method of identifying miR-31 targets by transcriptome analysis. The results of this study would enhance our present understanding ofmiR-31 function insea cucumber immune regulation. PMID- 26892794 TI - Transcriptome analysis demonstrate widespread differential expression of long noncoding RNAs involve in Larimichthys crocea immune response. AB - Long noncoding RNAs (lncRNAs) are a class of transcripts that longer than 200 bp and do not encode proteins. Recent genome-wide studies of vertebrate transcriptomes have annotated lncRNAs that are expressed in various tissues and development stages. The draft genome and several transcriptome sequencing data sets have been collected for the study of protein-coding genes in large yellow croaker (Larimichthys crocea), but little is known about the expression and functional roles of lncRNAs in this species. In order to obtain a catalog of lncRNAs for large yellow croaker, several RNA-seq datasets were integrated from various tissues including egg, muscle, liver, and spleen. A total of 48,953 high confidence transcripts were reconstructed in 38,017 loci, recovering the most of expressed reference transcripts while thousands of novel expressed loci have been identified. The tissue expression profile revealed that most lncRNAs were specifically enriched in different tissues. A stringent set of 210 lncRNAs were identified as being specifically expressed in spleen and potentially involved in immune response. Our study first systematically identify lncRNAs in large yellow croaker, benefiting the future genomic study of this species. PMID- 26892792 TI - Hearing loss in workers exposed to epoxy adhesives and noise: a cross-sectional study. AB - OBJECTIVES: Epoxy adhesives contain organic solvents and are widely used in industry. The hazardous effects of epoxy adhesives remain unclear. The objective of this study was to investigate the risk of hearing loss among workers exposed to epoxy adhesives and noise. DESIGN: Cross-sectional study. METHODS: For this cross-sectional study, we recruited 182 stone workers who were exposed to both epoxy adhesives and noise, 89 stone workers who were exposed to noise only, and 43 workers from the administrative staff who had not been exposed to adhesives or noise. We obtained demographic data, occupational history and medical history through face-to-face interviews and arranged physical examinations and pure-tone audiometric tests. We also conducted walk-through surveys in the stone industry. A total of 40 representative noise assessments were conducted in 15 workplaces. Air sampling was conducted at 40 workplaces, and volatile organic compounds were analysed using the Environmental Protection Agency (EPA) TO-15 method. RESULTS: The mean sound pressure level was 87.7 dBA (SD 9.9). The prevalence of noise induced hearing loss was considerably increased in the stone workers exposed to epoxy adhesives (42%) compared with the stone workers who were not exposed to epoxy adhesives (21%) and the administrative staff group (9.3%). A multivariate logistic regression analysis revealed that exposure to epoxy adhesives significantly increased the risk of hearing loss between 2 and 6 kHz after adjusting for age. Significant interactions between epoxy adhesives and noise and hearing impairment were observed at 3, 4 and 6 kHz. CONCLUSIONS: Epoxy adhesives exacerbate hearing impairment in noisy environments, with the main impacts occurring in the middle and high frequencies. PMID- 26892796 TI - Modulating effects of orally supplied Euglena gracilis on the physiological responses of the freshwater mussel Diplodon chilensis, exposed to sewage water pollution in a Patagonian river (Argentina). AB - In order to test if orally supplied Euglena sp. cells modulate the physiological status of bivalves during bioremediation procedures, we evaluated the effect of Euglena gracilis diet on the immune response, oxidative balance and metabolic condition of Diplodon chilensis exposed to sewage water pollution. Mussels were fed for 90 days with E. gracilis (EG) or Scenedesmus vacuolatus (SV, control diet), and then exposed for 10 days at three sites along the Pocahullo river basin: 1) an unpolluted site, upstream of the city (control, C); 2) upstream (UpS) and 3) downstream (DoS) from the main tertiary-treated sewage discharge, in the city of San Martin de los Andes, Northwest Patagonia, Argentina. Our results show that the total hemocyte number decreases while pollution load increases along the river course for both, EG and SV mussels. Phagocytic activity is higher in EG mussels than in SV ones under all conditions. Reactive oxygen species (ROS) production in hemocytes increases with the increase in the pollution load, being significantly higher for EG mussels than for SV ones at DoS; no changes are observed for total oxyradical scavenging capacity (TOSC). Hemocytes' viability is increased for E. gracilis diet at C and remains unchanged in this group of mussels when exposed at the polluted sites. Lysosomal membrane stability is higher in EG mussels than in SV ones for all conditions, although it is decreased at polluted sites compared with that at C. Antioxidant (catalase) and detoxifying (gluthatione S-transferase) defenses are generally lower in gills and digestive gland of EG mussels than in SV ones. Lipid peroxidation (TBARS) is evident in gills of EG mussels at C, and in digestive gland of the same group, at all the sites. Gill mass factor (GF) is affected by the E. gracilis diet; it is increased at C and decreased at polluted sites when compared with that of SV ones. Digestive gland mass factor (DGF) is higher in EG mussels than in SV ones. In D. chilensis, continuous and long term feeding with E. gracilis cells favors immune response and reduces the damage caused by sewage pollution exposure on hemocytes. Nevertheless, diet and transplantation procedures may produce negative effects on the oxidative balance of gills and digestive gland and should be taken into account for bioremediation strategies. PMID- 26892795 TI - A tandem-repeat galectin-9 involved in immune response of yellow catfish, Pelteobagrus fulvidraco, against Aeromonas hydrophila. AB - Galectins exclusively recognize and bind beta-galactoside on cell surface by carbohydrate recognition domain (CRD). In spite of extensive study of mammalian galectin importance in immune system, little is known about that of fish. To study the immune response of yellow catfish to pathogens, a tandem-repeat galectin-9 from yellow catfish was identified and named PfGAL9. Its full-length cDNA was 1314 bp, including a 117 bp of 5' untranslated region (UTR), a 951 bp of open reading frame (ORF), and a 246 bp of 3' UTR. The ORF encoded 316 amino acids (35.12 KDa), shared the highest 78% identity with the predicted galectin-9 of Ictalurus punctatus. This protein possessed two distinct CRDs with two highly conserved sugar binding motifs. Quantitative PCR showed that PfGAL9 was lowly expressed in skin, gill, fin, muscle, heart, and intestine, highly expressed in tested immune tissues (head kidney, trunk kidney, liver, spleen, and blood) in normal body. After inactivated Aeromonas hydrophila challenge, PfGAL9 was remarkably increased in head kidney and liver in a time-dependent manner. The recombinant protein was expressed in Escherichia coli, which not only agglutinated but also bond all examined bacteria. The binding activities are consistent with the size of aggregates formed by agglutinated bacteria. The agglutination must depend on its direct interaction with bacteria. These results suggested that PfGAL9 was involved in the innate immune response against bacterial infection and clearance of pathogens in yellow catfish. PMID- 26892798 TI - One year in review: ultrasound in arthritis. AB - Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic and musculoskeletal diseases. This non-invasive imaging modality is a valuable point-of-care tool to accurately evaluate intra-articular and periarticular structures involved in a wide range of rheumatic diseases in adults and children. In addition, MSUS is an invaluable bedside aid for guiding accurate and safe musculoskeletal aspirations, injections and biopsies. This review provides an overview of the literature of the last year on the role of MSUS in arthritis. PMID- 26892797 TI - Missing the target: DNAk is a dominant epitope in the humoral immune response of channel catfish (Ictalurus punctatus) to Flavobacterium columnare. AB - Vaccination remains a viable alternative for bacterial disease protection in fish; however additional work is required to understand the mechanisms of adaptive immunity in the channel catfish. To assess the humoral immune response to Flavobacterium columnare; a group of channel catfish were first immunized with F. columnare LV-359-01 cultured in iron-depleted media, before being challenged with wild type F. columnare LV-359-01. The immunization protocol did not confer increased protection against F. columnare; however both control and immunized responders generated serum and skin IgM antibodies against F. columnare proteins. Western blot analyses of individuals from both groups showed that IgM antibodies were generated to the same 70 kDa extracellular protein, which was identified to be the bacterial chaperonin protein DNAk. Antibodies generated were cross reactive to DNAk proteins found in other gram negative bacteria. Our data suggests that DNAk is the dominant epitope in the channel catfish B-cell response to F. columnare. PMID- 26892799 TI - Association between maternal and umbilical cord serum dipeptidyl peptidase IV in pregnant women with and without gestational diabetes mellitus. AB - AIM: The aim of the present study was to investigate maternal and umbilical cord serum dipeptidyl peptidase IV (DPP4) concentrations in women with and without gestational diabetes mellitus (GDM), and to evaluate a potential correlation between neonatal anthropometry and cord serum DPP4 concentration. METHODS: Twenty eight GDM and 25 normal glucose tolerance (NGT) pregnant women were recruited into the present study. Maternal and umbilical cord serum DPP4 concentrations were measured by enzyme immunoassay. Maternal and neonatal clinical data, glucose, insulin, triglyceride, cholesterol, high-density lipoprotein, and low density lipoprotein were recorded and measured for analysis. RESULTS: A statistically significant positive correlation was observed between maternal and umbilical cord serum DPP4 concentrations (Spearman's correlation coefficient = 0.804, P < 0.001; partial correlation coefficient r' = 0.884, P < 0.001). No significant difference was seen when comparing DPP4 concentrations for the GDM and NGT groups' maternal serum (P = 0.498), or their umbilical cord serum (P = 0.449). No statistically significant correlations were observed between umbilical cord serum DPP4 concentration and the presence of neonatal anthropometry or metabolic factors. CONCLUSION: Umbilical cord serum DPP4 concentration is associated with maternal DPP4 concentration, but is not related to neonatal anthropometry or metabolic factors. No significant difference was observed between the GDM and NGT groups in maternal or cord serum DPP4 concentrations. PMID- 26892800 TI - QSAR Toolbox - workflow and major functionalities. AB - The OECD QSAR Toolbox is a software application intended to be used by governments, the chemical industry and other stakeholders in filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals. The development and release of the Toolbox is a cornerstone in the computerization of hazard assessment, providing an 'all inclusive' tool for the application of category approaches, such as read-across and trend analysis, in a single software application, free of charge. The Toolbox incorporates theoretical knowledge, experimental data and computational tools from various sources into a logical workflow. The main steps of this workflow are substance identification, identification of relevant structural characteristics and potential toxic mechanisms of interaction (i.e. profiling), identification of other chemicals that have the same structural characteristics and/or mechanism (i.e. building a category), data collection for the chemicals in the category and use of the existing experimental data to fill the data gap(s). The description of the Toolbox workflow and its main functionalities is the scope of the present article. PMID- 26892802 TI - The Box Plots Alternative for Visualizing Quantitative Data. PMID- 26892803 TI - Abnormal Neural Basis of Emotional Conflict Control in Treatment-Resistant Depression. AB - Emotional conflict has received increased attention as a research topic. The objective of this study is to confirm that the processing of emotional conflict is impaired in treatment-resistant depression (TRD). We compared the event related potentials of 17 patients with TRD and 17 healthy controls during the face-word Stroop task, which is an effective way of assessing the effects of emotional conflict directly. Compared with healthy controls, the accuracy scores of the TRD patients were lower in both "congruent stimuli" and "incongruent stimuli" conditions, and their response times were longer. The TRD patients also had larger N2 amplitudes over the frontal region, regardless of stimulus condition, which might reflect that TRD patients pay more attention to emotional information. A larger P3 amplitude over the frontal region for "incongruent stimuli minus congruent stimuli" was also found among patients with TRD, which indicates interference effects in the Stroop task. The results of this study provide novel behavioral and neurophysiological evidence of anomalies in cognitive inhibition among patients with TRD using the word-face task. These findings not only improve our understanding of deficient inhibition in TRD, but also pave the way for a cognitive neuropsychiatric model of depression. PMID- 26892801 TI - A novel esterase from a marine mud metagenomic library for biocatalytic synthesis of short-chain flavor esters. AB - BACKGROUND: Marine mud is an abundant and largely unexplored source of enzymes with unique properties that may be useful for industrial and biotechnological purposes. However, since most microbes cannot be cultured in the laboratory, a cultivation-independent metagenomic approach would be advantageous for the identification of novel enzymes. Therefore, with the objective of screening novel lipolytic enzymes, a metagenomic library was constructed using the total genomic DNA extracted from marine mud. RESULTS: Based on functional heterologous expression, 34 clones that showed lipolytic activity were isolated. The five clones with the largest halos were identified, and the corresponding genes were successfully overexpressed in Escherichia coli. Molecular analysis revealed that these encoded proteins showed 48-79 % similarity with other proteins in the GenBank database. Multiple sequence alignment and phylogenetic tree analysis classified these five protein sequences as new members of known families of bacterial lipolytic enzymes. Among them, EST4, which has 316 amino acids with a predicted molecular weight of 33.8 kDa, was further studied in detail due to its strong hydrolytic activity. Characterization of EST4 indicated that it is an alkaline esterase that exhibits highest hydrolytic activity towards p-nitrophenyl butyrate (specific activity: 1389 U mg(-1)) at 45 degrees C and pH 8.0. The half life of EST4 is 55 and 46 h at 40 and 45 degrees C, respectively, indicating a relatively high thermostability. EST4 also showed remarkable stability in organic solvents, retaining 90 % of its initial activity when incubated for 12 h in the presence of hydrophobic alkanes. Furthermore, EST4 was used as an efficient whole cell biocatalyst for the synthesis of short-chain flavor esters, showing high conversion rate and good tolerance for high substrate concentrations (up to 3.0 M). These results demonstrate a promising potential for industrial scaling-up to produce short-chain flavor esters at high substrate concentrations in non-aqueous media. CONCLUSIONS: This manuscript reports unprecedented alcohol tolerance and conversion of an esterase biocatalyst identified from a marine mud metagenomic library. The high organic solvent tolerance and thermostability of EST4 suggest that it has great potential as a biocatalyst. PMID- 26892805 TI - Electron-phonon interaction and pairing mechanism in superconducting Ca intercalated bilayer graphene. AB - Using the ab initio anisotropic Eliashberg theory including Coulomb interactions, we investigate the electron-phonon interaction and the pairing mechanism in the recently-reported superconducting Ca-intercalated bilayer graphene. We find that C6CaC6 can support phonon-mediated superconductivity with a critical temperature Tc = 6.8-8.1 K, in good agreement with experimental data. Our calculations indicate that the low-energy Caxy vibrations are critical to the pairing, and that it should be possible to resolve two distinct superconducting gaps on the electron and hole Fermi surface pockets. PMID- 26892804 TI - Point-of-care coagulometry in prehospital emergency patients--are international normalized ratios useful? PMID- 26892806 TI - Isolation of bacteria in semen and evaluation of antibiotics in extender for cryopreservation of buffalo (Bubalus bubalis) bull spermatozoa. AB - This study was designed to investigate the occurrence of bacterial species in water buffalo semen at the time of collection/processing and to assess the efficacy of some selected antibiotics (GTLS; gentamycin, tylosin and linco spectin or SP; streptomycin and penicillin) in cryodiluent on bacterial control and quality including in vivo fertility of buffalo spermatozoa. For this purpose, four experiments were conducted. In experiment 1, a total of 11 bacterial species were isolated from buffalo ejaculates. In experiment 2, total aerobic bacterial counts at post dilution and thawing were lower (P < 0.05) in GTLS than in SP or control. The majority of the bacterial isolates from ejaculates were more susceptible to GTLS than SP. In experiment 3, sperm acrosome integrity was higher (P < 0.05) in GTLS and SP compared to control. In experiment 4, the in vivo fertility results for GTLS were higher (P < 0.05) than that for SP. In conclusion, a number of bacterial species were isolated from the bubaline semen, which requires an efficient control before its use in artificial insemination program. The GTLS combination of antibiotics may be incorporated into a freezing extender/protocol without compromising the post-thaw quality and in vivo fertility of buffalo bull spermatozoa. PMID- 26892807 TI - Structural characteristics of the optic nerve head influencing human retinal venous pulsations. AB - The relationship between structural characteristics of the optic nerve head and venous pulsations in the human eye remain unknown. Using photoplethysmographic techniques we investigated whether properties of the human retinal veins and their surrounding structures influence venous pulsation. 448 locations of venous pulsation were analysed from 26 normal human eyes. Green channel densitometry derived from video recordings of venous pulsations were used to generate a map of venous pulsation amplitudes along retinal veins. Optical coherence tomography was used to perform quantitative measurements of tissue characteristics at sites of high and low amplitude points as well as in a second analysis, at maximal amplitude pulsation sites from superior and inferior halves of the eyes. Structural characteristics measured included venous diameter, distance from pulsation point to cup margin, vessel length from pulsation point to vein exit, tissue thickness overlying vein, optic disc diameter and presence of a proximal arteriovenous crossing. Increasing venous pulsation amplitudes were associated with larger applied ophthalmodynamometry force, increasing venous diameter, and decreasing absolute cup margin distance (all p < 0.001). Increasing distance of maximal amplitude pulsation point to cup margin was associated with the presence of a proximal arteriovenous crossing, increasing venous diameter, and decreasing tissue depth (all p <= 0.001). Venous diameter and tissue depth alter venous compliance, which is likely to be a major factor determining sites of venous pulsation. PMID- 26892808 TI - Prenatal diagnosis of tethered spinal cord associated with sacrococcygeal teratoma. AB - Tethered spinal cord is mostly caused by myelomeningocele and lipomyelomeningocele, while dermal sinus tract, diastematomyelia, lipoma, tumor, thickened/tight filum terminale, spinal trauma, and spinal surgery are among the other causes. Prenatal diagnosis of tethered cord has been reported, and it is usually associated with neural tube defects. We present an atypical presentation of a tethered spinal cord, which was associated with a sacrococcygeal teratoma and was diagnosed in the 23rd week of pregnancy by ultrasonography. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:506-509, 2016. PMID- 26892809 TI - Cellular apoptosis susceptibility (CAS) is overexpressed in thyroid carcinoma and maintains tumor cell growth: A potential link to the BRAFV600E mutation. AB - Thyroid carcinoma is among the most common malignant endocrine neoplasms with a rising incidence. Genetic alterations occurring in thyroid cancer frequently affect the RAS/RAF/MEK/ERK-pathway such as the oncogenic, kinase-activating BRAF(V600E) mutation. Nuclear transport receptors including importins and exportins represent an important part of the nuclear transport machinery providing nucleo-cytoplasmic exchange of macromolecules. The role of nuclear transport receptors in the development and progression of thyroid carcinomas is largely unknown. Here, we studied the expression and function of the exportin cellular apoptosis susceptibility (CAS) in thyroid carcinogenesis and its link to the BRAF(V600E) mutation. By using immunohistochemistry (IHC) we found significantly increased IHC scores of CAS in primary papillary (PTC) and medullary (MTC), but not in follicular (FTC) thyroid carcinoma compared to non tumorous (NT) thyroid tissue. Interestingly, metastases of the aforementioned subtypes including FTC showed a strong CAS positivity. Among PTCs we observed that CAS immunoreactivity was significantly higher in the tumors harboring the BRAF(V600E) mutation. Furthermore, depletion of CAS by RNAi in the BRAF(V600E) positive PTC cell line B-CPAP led to reduced tumor cell growth measured by crystal violet assays. This phenotype could be attributed to reduced proliferation and increased cell death as assayed by BrdU ELISAs and immunoblotting for PARP-cleavage, respectively. Finally, we found additive effects of CAS siRNA and vemurafenib treatment in B-CPAP cells. Collectively, these data suggest that CAS overexpression in thyroid carcinoma depends on the subtype and the disease stage. Our findings also indicate that CAS maintains PTC cell proliferation and survival. Targeting CAS could represent a potential therapeutic approach particularly in combination with BRAF inhibitors such as vemurafenib in BRAF(V600E)-positive tumors. PMID- 26892810 TI - The Role of Manual Aspiration Thrombectomy in Patients Undergoing Primary Percutaneous Coronary Intervention for STEMI. AB - In STEMI, primary PCI restores macrovascular coronary blood flow effectively but microvascular perfusion remains a challenge. Thrombus has the potential to embolize to the microvasculature limiting effective coronary blood flow. Thrombus burden is associated with a higher mortality and manual aspiration thrombectomy has the potential to reduce thrombus burden. The first large trial of routine aspiration thrombectomy (TAPAS, N = 1071) showed an improvement in myocardial blush and an unexpected reduction in mortality. Reinforcing the enthusiasm for this finding meta-analysis of small trials also showed a reduction in mortality, which led to routine manual thrombectomy becoming a class IIa recommendation in the American and European Guidelines for STEMI. Subsequently; however, large trials such as TOTAL (N = 10,732) and TASTE (N = 7244) and meta-analysis showed an increase in the risk of stroke with routine manual thrombectomy but no improvement in mortality, myocardial infarction, stent thrombosis, or severe heart failure. As such, manual thrombectomy should not be routinely used instead saving it as a bailout procedure as indicated. PMID- 26892812 TI - Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction Evaluated by Mid-Wall Mechanics in Rheumatoid Arthritis. AB - OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased cardiovascular event rate, mainly due to the arterial stiffness which leads to coronary atherosclerosis and concentric left ventricular (LV) geometry. These conditions predispose to LV systolic dysfunction (LVSD), which can be detected by stress-corrected mid-wall shortening (sc-MS), an early prognosticator of cardiovascular events in asymptomatic patients with arterial hypertension and/or diabetes. In these subjects, sc-MS is frequently impaired even though LV ejection fraction (LVEF) is preserved. In this study, we analyzed the prevalence and the factors associated with asymptomatic LVSD measured by sc-MS among patients with RA and verified whether RA per se was independently related to LVSD. METHODS: We prospectively recruited 198 outpatients with RA without overt cardiac disease between January and June 2014 and compared them to 198 controls matched for age, gender, body mass index, and prevalence of hypertension and diabetes. sc-MS was taken as index of LVSD and considered impaired if <86.5%. RESULTS: Impaired sc-MS was detected in 110 (56%) RA patients and in 30 (15%) controls (P < 0.001), whereas LVEF was impaired (value <50%) in six (3%) RA patients and in two (1%) controls (P = ns). Multiple logistic regression analysis revealed that RA was independently associated with impaired sc-MS (Exp beta 2.01 [CI 1.12-3.80], P = 0.02) together with increased LV mass and concentric geometry. CONCLUSIONS: More than half RA patients without overt cardiac disease have LVSD detectable by sc MS. RA emerges as a condition closely related to LVSD. These findings might explain the high risk for adverse cardiovascular events in RA patients. PMID- 26892811 TI - Canonical NF-kappaB signaling in hepatocytes acts as a tumor-suppressor in hepatitis B virus surface antigen-driven hepatocellular carcinoma by controlling the unfolded protein response. AB - Chronic hepatitis B virus (HBV) infection remains the most common risk factor for hepatocellular carcinoma (HCC). Efficient suppression of HBV viremia and necroinflammation as a result of nucleos(t)ide analogue treatment is able to reduce HCC incidence; nevertheless, hepatocarcinogenesis can occur in the absence of active hepatitis, correlating with high HBV surface antigen (HBsAg) levels. Nuclear factor kappaB (NF-kappaB) is a central player in chronic inflammation and HCC development. However, in the absence of severe chronic inflammation, the role of NF-kappaB signaling in HCC development remains elusive. As a model of hepatocarcinogenesis driven by accumulation of HBV envelope polypeptides, HBsAg transgenic mice, which show no HBV-specific immune response, were crossed to animals with hepatocyte-specific inhibition of canonical NF-kappaB signaling. We detected prolonged, severe endoplasmic reticulum stress already at 20 weeks of age in NF-kappaB-deficient hepatocytes of HBsAg-expressing mice. The unfolded protein response regulator binding immunoglobulin protein/78-kDa glucose regulated protein was down-regulated, activating transcription factor 6, and eIF2alpha were activated with subsequent overexpression of CCAAT/enhancer binding protein homologous protein. Notably, immune cell infiltrates and liver transaminases were unchanged. However, as a result of this increased cellular stress, insufficient hepatocyte proliferation due to G1 /S-phase cell cycle arrest with overexpression of p27 and emergence of ductular reactions was detected. This culminated in increased DNA damage already at 20 weeks of age and finally led to 100% HCC incidence due to NF-kappaB inhibition. CONCLUSION: The role of canonical NF-kappaB signaling in HCC development depends on the mode of liver damage; in the case of HBsAg-driven hepatocarcinogenesis, NF-kappaB in hepatocytes acts as a critical tumor suppressor by augmenting the endoplasmic reticulum stress response. PMID- 26892813 TI - Long-Term Experiences in Cash and Counseling for Young Adults with Intellectual Disabilities: Familial Programme Representative Descriptions. AB - BACKGROUND: Our aim was to explore previously unknown long-term outcomes of self directed personal care services for young adults with intellectual disabilities and limitations in activities of daily living. MATERIALS AND METHODS: The present authors utilized participatory action research and qualitative content analysis in interviewing 11 unpaid familial programme representatives of young adults with intellectual disabilities, ages 23-34, who were eligible for income-based Medicaid and enrolled five or more years in a Cash and Counseling-based programme of self-direction in the United States. RESULTS: Young adults are represented as receiving services and supports in a supportive and stable environment, with previously identified short-term programme benefits evident over the long-term. Young adults are also transitioning to adulthood at home with their families as primary social support and caregivers, bridging a service gap. CONCLUSIONS: Our results show that self-direction helps meet these young adults' personal care and community engagement needs over time. PMID- 26892814 TI - Does selection in a challenging environment produce Nile tilapia genotypes that can thrive in a range of production systems? AB - This study assessed whether selection for high growth in a challenging environment of medium salinity produces tilapia genotypes that perform well across different production environments. We estimated the genetic correlations between trait expressions in saline and freshwater using a strain of Nile tilapia selected for fast growth under salinity water of 15-20 ppt. We also estimated the heritability and genetic correlations for new traits of commercial importance (sexual maturity, feed conversion ratio, deformity and gill condition) in a full pedigree comprising 36,145 fish. The genetic correlations for the novel characters between the two environments were 0.78-0.99, suggesting that the effect of genotype by environment interaction was not biologically important. Across the environments, the heritability for body weight was moderate to high (0.32-0.62), indicating that this population will continue responding to future selection. The estimates of heritability for sexual maturity and survival were low but significant. The additive genetic components also exist for FCR, gill condition and deformity. Genetic correlations of harvest body weight with sexual maturity were positive and those between harvest body weight with FCR were negative. Our results indicate that the genetic line selected under a moderate saline water environment can be cultured successfully in freshwater systems. PMID- 26892815 TI - Gastrointestinal stability of therapeutic anti-TNF alpha IgG1 monoclonal antibodies. AB - Monoclonal antibodies (mAbs) are highly effective therapeutic agents, administered exclusively by the parenteral route owing to their previously documented instability in the gastrointestinal (GI) tract when delivered orally. To investigate the extent of the validity of this assumption, the stability of the tumor necrosis factor alpha (TNF-alpha) neutralizing IgG1 mAbs, infliximab and adalimumab, was studied in human GI conditions. In gastric fluid, infliximab and adalimumab degraded rapidly, with complete degradation occurring within 1 min. In small intestinal fluid, the molecules were shown to be more stable, but nonetheless degraded within a short time frame of 30 min. Investigations into the mechanisms responsible for infliximab and adalimumab instability in the small intestine revealed that the proteolytic enzyme elastase, and to a lesser extent the enzymes trypsin and chymotrypsin, was responsible for their degradation. By contrast, in the human colon, 75% and 50% of the dose of infliximab and adalimumab, respectively, were intact after 60 min, with conversion of mAbs into F(ab')2 Fab and Fc fragments detected in colonic conditions. These data indicate that therapeutic IgG1 antibodies are more stable in the colon than in the upper GI tract, therefore highlighting the potential for oral delivery of anti-TNF alpha mAbs targeted to the colon. PMID- 26892816 TI - Proteomics in toxicology - Added value or waste of energies? PMID- 26892817 TI - Invasive Pasteurella multocida Infections - Report of Five Cases at a Minnesota Hospital, 2014. AB - During October 2014, the Minnesota Department of Health was notified of five Hospital A patients with Pasteurella multocida bacteraemia; three had died. Human soft tissue infection with P. multocida typically results from cat or dog bites or scratches. Invasive infection, defined as a P. multocida isolate from a usually sterile site, is rare. We evaluated P. multocida isolations at Hospital A, compared with other Minnesota hospitals to understand invasive infection trends. A case was defined as clinically confirmed P. multocida in a Minnesota resident during 2012-2014. All hospital laboratories were queried; Fisher's exact test was used for comparison. Medical charts were reviewed for 2014 Hospital A patients with P. multocida infections. The Minnesota clinical laboratories survey response rate was 79% (63/80). At Hospital A, proportion of P. multocida isolates from usually sterile sites increased from 0% (0/2) during 2012 to 11% (1/9) during 2013, and to 86% (5/6) during 2014. The proportion of patients with P. multocida isolated from sterile sites was 35% (6/17) at Hospital A compared with 10% (58/583) statewide during 2012-2014 combined (P < 0.05). Among 2014 Hospital A patients with invasive P. multocida infection, all five were men; median age was 70 (range: 44-78) years. Four were temporally clustered within a 33-day period; three of those had bacteraemia on admission, making hospital acquisition possible in only one. Among five bacteraemia patients, four had cirrhosis and/or skin ulcerations, and three died. The proportion of invasive P. multocida cases was substantially higher at Hospital A during 2014. No epidemiologic links between patients were found. Three had known pet exposure. Collaborative educational efforts of chronically ill pet owners by physicians and veterinarians can acknowledge the health benefits of pet ownership, while minimizing risk for serious invasive zoonotic infections, including those caused by P. multocida. PMID- 26892818 TI - Ex Vivo Human Placental Perfusion Model for Analysis of Fetal Circulation in the Chorionic Plate. AB - OBJECTIVES: The purpose of this study was to develop an ex vivo placental perfusion model to assess changes in the umbilical artery systolic-to-diastolic (S/D) ratio due to progressive occlusion of the placental arterial system. METHODS: Ex vivo human placentas were connected to a computerized pulse duplicator mimicking pulsatile flow from the fetal heart. Doppler sonographic measurements were conducted on the umbilical and chorionic arteries of 25 mature placentas. Simulation of placental occlusion was performed by progressive ligature of the chorionic arteries, including one umbilical artery. The correlation between the umbilical artery S/D ratio and the severity of simulated placental occlusion was analyzed. RESULTS: The normal mean S/D ratio +/- SD decreased gradually along the chorionic plate from 2.66 +/- 0.47 at the cord insertion to 1.90 +/- 0.59 in generation IV of the chorionic vessels. The Doppler index initially increased slowly with simulated placental occlusion. Only when all 4 generations were occluded was the umbilical artery S/D ratio elevated. Complete occlusion of one umbilical artery resulted in a 39% increase in the umbilical artery S/D ratio. CONCLUSIONS: This unique model combining Doppler sonography with perfusion of an ex vivo placenta can be used for a better understudying of pathologic placental blood flow circulation. PMID- 26892819 TI - Unilateral Fetal Renal Abnormalities: Are They Really Isolated? AB - OBJECTIVES: Our objective was to describe the association between unilateral fetal renal abnormalities and other major anomalies that were not apparent in the second trimester. METHODS: A review of the ultrasound database identified fetuses with suspected unilateral renal agenesis, unilateral multicystic dysplastic kidney, and renal ectopia from 2005 to 2014. Neonatal records were reviewed to identify anomalies not suspected in the second trimester, and postnatal imaging studies were reviewed. Categorical data were compared by &x003C7;(2) analysis and the Fisher exact test. RESULTS: We identified 102 cases, including 36 with suspected renal agenesis, 28 with suspected multicystic dysplastic kidney, and 38 with suspected renal ectopia. There were 8 cases (7.8%) with major anomalies not suspected in the second trimester. In 5 cases (4.9%), there were no associated findings in the second trimester. There were no significant differences in the rates of unsuspected abnormalities between the 3 groups. There was a trend toward a higher rate of unsuspected anomalies in the cases with a single umbilical artery compared to those with a 3-vessel cord (28.6% vs 6.3%; P= .09). CONCLUSIONS: In fetuses with unilateral renal abnormalities, major anomalies that were not suspected in the second trimester were uncommon. However, patients should be aware of the possibility that other major anomalies could subsequently be identified, and the outcome may depend on more than postnatal renal function. PMID- 26892820 TI - Obstetric Ultrasound Efficiency and Accuracy Using a Protocol-Based Examination. AB - OBJECTIVES: Obstetric ultrasound imaging requires the acquisition of a standard set of maternal and fetal images. Our objective was to evaluate the impact of implementation of a protocol-based ultrasound examination on the duration of ultrasound examinations, examination completion, and accuracy of documentation. METHODS: We conducted a case-cohort study. Obstetric ultrasound examinations performed in the first, second, and third trimesters were reviewed before and after implementation of a protocol-based ultrasound examination. The duration of the ultrasound examination, number of missing required images, and documentation of missing images were abstracted from an image archival system. To account for clustering by sonographer, 3 mixed effects models with a fixed effect for protocol and a random intercept for sonographer were used to evaluate the effect on the total time of the examination, number of missing images, and whether missing images were documented. RESULTS: A total of 100 ultrasound examinations were compared: 50 before and 50 after implementation of the protocol. Statistically significant differences between outcomes before and after protocol implementation were observed for all outcomes. After implementation of the protocol, the average duration of ultrasound examinations decreased by 7.62 minutes (95% confidence interval [CI], 3.57-11.68 minutes); the number of missing images was reduced by 5.81 per examination (95% CI, 4.24-7.39); and proper documentation of missing images increased by 40.24% (95% CI, 22.77%-57.71%). CONCLUSIONS: Implementation of a software protocol-based ultrasound examination significantly improved the efficiency and accuracy of obstetric ultrasound examinations in this study. PMID- 26892821 TI - Sonography of Abdominal Pain in Children: Appendicitis and Its Common Mimics. AB - Abdominal pain is very common in the pediatric population (<18 years of age). Sonography is a safe modality that can often differentiate the frequently encountered causes of abdominal pain in children. This pictorial essay will discuss the sonographic findings of acute appendicitis, including the imaging appearance of a perforated appendicitis. It will also present the sonographic features of the relatively common mimics of appendicitis, such as mesenteric adenitis/gastroenteritis, intussusception, Meckel diverticulum, and ovarian torsion. PMID- 26892823 TI - Reply. PMID- 26892822 TI - Evanescent Hyperechoic Changes After Fine-Needle Aspiration Biopsy of the Thyroid in a Series With a Low Overall Prevalence of Complications. AB - OBJECTIVES: The purpose of this study was to assess the frequency of and risk factors for fine-needle aspiration biopsy (FNAB)-related complications in Japanese patients with thyroid nodules evaluated by standard FNAB techniques. METHODS: Six hundred fifty-three consecutive Japanese patients with 742 nodules who had undergone FNAB were enrolled. Nodule characteristics were evaluated, and thyroid volumes were measured. Fine-needle aspiration biopsy-related complications were identified on the basis of sonographic findings and patients' conditions after undergoing FNAB. Comparisons of patients' backgrounds and nodule characteristics were made between those with and without complications. RESULTS: The prevalence rates for FNAB-related complications, including acute transient thyroid swelling after FNAB and appearance of anechoic lesions, were 0.13% and 0.94%. In this study, we could not identify risk factors for FNAB-related complications. The sudden appearance of bright hyperechoic foci within the thyroid immediately after biopsy was reported as an FNAB-related unfamiliar appearance in 5 cases. Experimental FNA using resected porcine thyroid tissue suggested that the etiology of the hyperechoic appearance may be artificial air bubbles or reversed flow of aspirated fluid. CONCLUSIONS: Fine-needle aspiration biopsy-related complications are rare if preventive measures are performed and are not specific to Japanese patients with thyroid nodules. The sudden appearance of bright hyperechoic foci may be cause by contamination from air or fluid. PMID- 26892824 TI - Correlation Between Cervical Lengths Measured by Transabdominal and Transvaginal Sonography for Predicting Preterm Birth. AB - OBJECTIVES: Cervical length assessment is important for predicting preterm birth. Cervical length measurement using transabdominal sonography is more comfortable for the patient but has more limitations than transvaginal sonography. Our aim was to determine whether transabdominal sonography could identify those women who should undergo transvaginal sonography for prediction of preterm birth. METHODS: In this prospective study, women underwent cervical length measurements by transabdominal and transvaginal sonography between 20 and 29 gestational weeks and were followed until delivery. We assessed whether short cervical lengths on transabdominal sonography could predict short cervical lengths on transvaginal sonography and whether these measurements could predict preterm births (<34 gestational weeks). RESULTS: The mean cervical lengths were not significantly different between the techniques (mean +/- SD, 3.78 +/- 0.82 and 3.82 +/- 0.77 cm on transabdominal and transvaginal sonography, respectively; P = .09). The sensitivity of short cervical lengths (<2 cm) on transabdominal sonography for prediction of short cervical lengths on transvaginal sonography was 100%. The sensitivity, specificity, positive predictive value, negative predictive value, and relative risk of short cervical lengths (<2 cm) for predicting preterm birth were 21.4%, 98.68%, 50.00%, 95.32%, and 13.22 when using transabdominal sonography and 28.57%, 94.94%, 66.6%, 95.74%, and 17.78 when using transvaginal sonography, respectively. In an analysis that included cases with transabdominal sonography, the sensitivity of short cervical lengths for predicting preterm birth was increased. CONCLUSIONS: Women whose cervical lengths are measurable and long on transabdominal sonography may not need transvaginal sonography. Women whose cervical lengths are unmeasurable or short (<2 or <2.5 cm) on transabdominal sonography should undergo transvaginal sonography to measure cervical lengths for prediction of preterm birth. PMID- 26892825 TI - Transcranial Color-Coded Duplex Sonography: Another Option Besides the Blind Method. PMID- 26892826 TI - Use of mulberry-soybean intercropping in salt-alkali soil impacts the diversity of the soil bacterial community. AB - Diverse intercropping system has been used to control disease and improve productivity in the field. In this research, the bacterial communities in salt alkali soils of monoculture and intercropping mulberry and soybean were studied using 454-pyrosequencing of the 16S rDNA gene. The dominant taxonomic groups were Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Bacteroidetes, Planctomycetes and Gemmatimonadetes and these were present across all samples. However, the diversity and composition of bacterial communities varied between monoculture and intercropping samples. The estimated bacterial diversity (H') was higher with intercropping soybean than in monoculture soybean, whereas H' showed an opposite pattern in monoculture and intercropping mulberry. Populations of Actinobacteria, Acidobacteria, and Proteobacteria were variable, depending on growth of plants as monoculture or intercropped. Most of Actinobacteria and Chloroflexi were found in intercropping samples, while Acidobacteria and Proteobacteria were present at a higher percentage in monoculture samples. The plant diversity of aboveground and microbial diversity of belowground was linked and soil pH seemed to influence the bacterial community. Finally, the specific plant species was the major factor that determined the bacterial community in the salt-alkali soils. PMID- 26892829 TI - Cemented hemiarthroplasty in traumatic displaced femoral neck fractures and deep vein thrombosis: is there really a link? AB - INTRODUCTION: Traumatic displaced femoral neck fractures in the elderly can be treated with cemented or uncemented hemiarthroplasty with good outcomes. Earlier studies reported a higher incidence of deep vein thrombosis (DVT) associated with cemented prostheses in elective total hip or knee arthroplasty. In addition, the hypercoagulable state after a traumatic femoral neck fracture and possible thrombogenic properties of bone cement could put these patients at greater risk for thromboembolism. We aimed to compare the incidence of DVT and progression to pulmonary embolism (PE) or mortality in cemented and uncemented hemiarthroplasty. METHODS: The data of 271 patients treated with cemented or uncemented hemiarthroplasty after a traumatic displaced femoral neck fracture was retrospectively analysed for the incidence of DVT. The level of thrombosis, progression to PE and mortality were compared. RESULTS: There were 133 (49.1%) patients with cemented hemiarthroplasty, while 138 (50.9%) had uncemented hemiarthroplasty. The patients had an average age of 76.6 (range 53-99) years and 11 (4.1%) patients had DVT. There were no significant differences in development of DVT, level of thrombosis, PE and mortality regardless of whether a cemented or an uncemented prosthesis was used. CONCLUSION: Cemented hemiarthroplasty is not associated with higher risks of DVT, PE or mortality in patients with traumatic displaced femoral neck fracture. Cemented prostheses can be safely used for this group of patients. PMID- 26892828 TI - ALDH1A1 provides a source of meiosis-inducing retinoic acid in mouse fetal ovaries. AB - Substantial evidence exists that during fetal ovarian development in mammals, retinoic acid (RA) induces germ cells to express the pre-meiotic marker Stra8 and enter meiosis, and that these effects are prevented in the fetal testis by the RA degrading P450 enzyme CYP26B1. Nonetheless, the role of RA has been disputed principally because germ cells in embryos lacking two major RA-synthesizing enzymes, ALDH1A2 and ALDH1A3, remain able to enter meiosis. Here we show that a third RA-synthesizing enzyme, ALDH1A1, is expressed in fetal ovaries, providing a likely source of RA in the absence of ALDH1A2 and ALDH1A3. In ovaries lacking ALDH1A1, the onset of germ cell meiosis is delayed. Our data resolve the conundrum posed by conflicting published data sets and reconfirm the model that meiosis is triggered by endogenous RA in the developing ovary. PMID- 26892827 TI - Diffusion-weighted imaging outside the brain: Consensus statement from an ISMRM sponsored workshop. AB - The significant advances in magnetic resonance imaging (MRI) hardware and software, sequence design, and postprocessing methods have made diffusion weighted imaging (DWI) an important part of body MRI protocols and have fueled extensive research on quantitative diffusion outside the brain, particularly in the oncologic setting. In this review, we summarize the most up-to-date information on DWI acquisition and clinical applications outside the brain, as discussed in an ISMRM-sponsored symposium held in April 2015. We first introduce recent advances in acquisition, processing, and quality control; then review scientific evidence in major organ systems; and finally describe future directions. J. Magn. Reson. Imaging 2016;44:521-540. PMID- 26892833 TI - Case of lumbar disc hernia caused in the left L4 and L5 dermatomes after herpes zoster infection in the right L2 and L3 dermatomes. PMID- 26892832 TI - A Variety of Phase-Transition Behaviors in a Niccolite Series of [NH3 (CH2 )4 NH3 ][M(HCOO)3 ]2. AB - A niccolite series of [bnH2 (2+) ][M(HCOO)3 ]2 (bnH2 (2+) =1,4-butyldiammonium) shows four kinds of metal-dependent phase transitions, from high temperature para electric phases to low-temperature ferro-, antiferro-, glass-like, and para electric phases. The conformational flexibility of bnH2 (2+) and the different size, mass, and bonding character of the metal ion lead to various disorder-order transitions of bnH2 (2+) in the lattice and relevant framework modulations, thus different phase transitions and dielectric responses. The magnetic members display a coexistence or combination of electric and magnetic orderings in the low-temperature region. PMID- 26892830 TI - OCT-based label-free in vivo lymphangiography within human skin and areola. AB - Due to the limitations of current imaging techniques, visualization of lymphatic capillaries within tissue in vivo has been challenging. Here, we present a label free high resolution optical coherence tomography (OCT) based lymphangiography (OLAG) within human skin in vivo. OLAG enables rapid (~seconds) mapping of lymphatic networks, along with blood vessel networks, over 8 mm x 8 mm of human skin and 5 mm x 5 mm of human areola. Moreover, lymphatic system's response to inflammation within human skin is monitored throughout an acne lesion development over 7 days. The demonstrated results promise OLAG as a revolutionary tool in the clinical research and treatment of patients with pathologic conditions such as cancer, diabetes, and autoimmune diseases. PMID- 26892831 TI - Nonmagnetic band gap at the Dirac point of the magnetic topological insulator (Bi(1-x)Mn(x))2Se3. AB - Magnetic doping is expected to open a band gap at the Dirac point of topological insulators by breaking time-reversal symmetry and to enable novel topological phases. Epitaxial (Bi(1-x)Mn(x))2Se3 is a prototypical magnetic topological insulator with a pronounced surface band gap of ~100 meV. We show that this gap is neither due to ferromagnetic order in the bulk or at the surface nor to the local magnetic moment of the Mn, making the system unsuitable for realizing the novel phases. We further show that Mn doping does not affect the inverted bulk band gap and the system remains topologically nontrivial. We suggest that strong resonant scattering processes cause the gap at the Dirac point and support this by the observation of in-gap states using resonant photoemission. Our findings establish a mechanism for gap opening in topological surface states which challenges the currently known conditions for topological protection. PMID- 26892834 TI - Group precipitation and age hardening of nanostructured Fe-based alloys with ultra-high strengths. AB - The precipitation of nanoparticles plays a key role in determining the properties of many structural materials, and the understanding of their formation and stabilization mechanisms has been a long standing interest in the material field. However, the critical issues involving the group precipitation of various nanoparticles and their cooperative hardening mechanism remain elusive in the newly discovered Fe-based alloys with nanostructures. Here we quantitatively elucidate the nucleation mechanism, evolution kinetics and hardening effects of the group-precipitated nanoparticles in the Fe-Cu-Ni-Al-based alloys by atom probe tomography together with both first-principles and thermodynamic calculations. Our results provide the compelling evidence for two interesting but complex group precipitation pathways of nanoparticles, i.e., the Cu-rich and NiAl based precipitations. The co-existence of the two precipitation pathways plays a key role in age hardening kinetics and ultimately enhances the hardening response, as compared to the single particle type of strengthening, therefore providing an effective new approach for strengthening materials for structural applications. PMID- 26892835 TI - Recombinant Patterns of Nine Novel HIV-1 Recombinant Strains Identified in Hebei Province, China. AB - We found cluster 1 and cluster 2 that were identified as two potential circulating recombinant forms (CRFs) by analyzing the recombinant breakpoints and phylogenetic tree. Three sequences composed of CRF01_AE, subtype C, and potential subtype B (N/A) in cluster 1 had nearly identical recombinant breakpoints, and four sequences composed of CRF01_AE and subtype B in cluster 2 possessed identical breakpoints. Demographic characteristics indicated that there were no epidemiological linkages among three subjects in cluster 1 and four subjects in cluster 2, respectively. Likewise, two unique recombinant forms (URFs) were found in this study: one URF was composed of subtype C and subtype B, and subtype B was inserted into a backbone of subtype C; another URF was composed of subtype C, subtype B, CRF01_AE, and subtype A2. It was inferred that the potential novel CRFs and URFs have spread into general populations, suggesting that the series research of novel recombinant strains will be a priority for our researches in the future. PMID- 26892836 TI - Association between health status and long-term mortality after percutaneous revascularization of peripheral artery disease. AB - OBJECTIVES: To explore the association of health status change and long-term survival among patients with symptomatic peripheral artery disease (PAD). BACKGROUND: Early gains in health status after successful endovascular therapy (EVT) for symptomatic PAD can be maintained up to 1 year. Whether such health status improvements are associated with long-term survival benefits is unknown. METHODS: Between February 2001 and August 2004, 258 patients with symptomatic PAD treated with EVT participated in a prospective study evaluating baseline and 1 year health status using the Peripheral Artery Questionnaire (range 0-100, higher scores = better). All-cause mortality was assessed for all patients at a median of 9.4 years following EVT. RESULTS: The mean age at enrollment was 68 +/- 11 years; 61% were male, 97% were Caucasian, and 38% had diabetes. Patients with a clinically meaningful health status improvement (>=8 points) 1 year after their index procedure (79%) were identified as responders. Responders had a significantly better 10 year survival compared with nonresponders (60% vs 38%, p = 0.025). Responder status was associated with a survival advantage that persisted in risk-adjusted analysis (adjusted hazard ratio for long-term mortality, 0.66 [95% CI, 0.45-0.97]; p = 0.036). CONCLUSIONS: Among patients with symptomatic PAD undergoing EVT, improvement of PAD-specific health status at 1 year follow-up was associated with improved long-term survival. Whether additional treatment for patients with poor response to EVT could improve long term survival warrants further investigation. (c) 2016 Wiley Periodicals, Inc. PMID- 26892837 TI - Drawn to danger: trait anger predicts automatic approach behaviour to angry faces. AB - Most people automatically withdraw from socially threatening situations. However, people high in trait anger could be an exception to this rule, and may even display an eagerness to approach hostile situations. To test this hypothesis, we asked 118 participants to complete an approach-avoidance task, in which participants made approach or avoidance movements towards faces with an angry or happy expression, and a direct or averted eye gaze. As expected, higher trait anger predicted faster approach (than avoidance) movements towards angry faces. Crucially, this effect occurred only for angry faces with a direct eye gaze, presumably because they pose a specific social threat, in contrast to angry faces with an averted gaze. No parallel effects were observed for happy faces, indicating that the effects of trait anger were specific to hostile stimuli. These findings suggest that people high in trait anger may automatically approach hostile interaction partners. PMID- 26892838 TI - Recurrent parotid swelling secondary to masseter muscle hypertrophy: a multidisciplinary diagnostic and therapeutic approach. AB - PURPOSE: To present a patient with an atypical recurrent parotid swelling due to masseter muscle hypertrophy and the diagnostic/therapeutic assessment to treat this condition. CASE REPORT: A patient referring recurrent right facial swelling underwent a complete multidisciplinary assessment of the parotid region that revealed masseter muscle hypertrophy, confirmed by means of clinical (otolaryngological and gnathological evaluation), radiological (utrasonography, dynamic magnetic resonance imaging, and cone beam computed tomography), instrumental (electromyography to evaluate the right masseter muscle function and kinesiography to evaluate maximum right deflection - MaxRDefl and maximum opening - MaxMO) and sialendoscopy assessment where T0 indicates the pre-treatment values. All electromyographic and kinesiographic parameters were evaluated six months after the orthodontic application of a neuromuscular orthosis at T1. At T1, the effectiveness of the orthodontic therapy was demonstrated by the complete resolution of symptoms, and instrumental results documented more efficient muscle activity at rest and during clenching and a better mandibular position. At EMG T1, the resting and post-TENS values were, respectively, 1.2 and 1.8 microV. At kinesiography, MaxRDefl increased from 10.2 (T0) to 10.5 mm (T1); maxMO increased from 41.2 (T0) to 48 mm (T1). CONCLUSION: The proposed multidisciplinary assessment based on otolaryngological, gnathological, and radiological evaluation may be useful in the case of recurrent parotid swelling secondary to masseter muscle hypertrophy to plan an appropriate management with a removable neuromuscular orthosis. PMID- 26892839 TI - Induction of cell self-organization on weakly positively charged surfaces prepared by the deposition of polyion complex nanoparticles of thermoresponsive, zwitterionic copolymers. AB - We have developed inducible cell self-organization through weakly positively charged culture surfaces. In this study, a thermoresponsive and zwitterionic copolymer comprised of N,N-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA) (PDMAEMA-co-PMA; Mn: ~9.7 * 104 g/mol; PDMAEMA/PMA ratio: 10) was designed for inducing cell self-organization. The copolymer formed single polymer-derived polyion complex (sPIC) nanoparticles following dissolution in an aqueous solution. The sPIC nanoparticles had a positive charge (ca. 25 mV). Self organization occurred in adipose-derived vascular stromal cell monolayers cultivated on sPIC-deposited surfaces. There were dramatic morphological changes of these cells with the formation of capillary-like networks and single-cell aggregates with little cytotoxicity. This was a significant improvement compared with cells grown on previously developed surfaces deposited with PIC, a mixture of PDMAEMA and plasmid DNA. Thus, sPICs of PDMAEMA-co-PMA may allow for the accurate evaluation of a variety of cell behaviors with less cytotoxicity, and may facilitate additional potential medical applications such as cell-based therapy and drug discovery. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1009-1015, 2017. PMID- 26892840 TI - A peptide hydrogel derived from a fragment of human cardiac troponin C. AB - The human cardiac troponin C peptide fragment H-V(9)EQLTEEQKNEFKAAFDIFVLGA(31) OH, which covers helix-A in the native protein, self-assembles into beta-sheet fibrils in solution. These fibrils further entangle to give a hydrogel. This peptide may therefore serve as a template for development of novel biomaterials. PMID- 26892841 TI - Emerging problems of data quality in citizen science. PMID- 26892843 TI - Predictors of poor outcome in patients with posterior reversible encephalopathy syndrome. AB - PURPOSE: Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome that, although characteristically reversible, can be fatal or result in long-term disability in a subset of patients. Our aim was to identify factors associated with poor discharge outcome in PRES patients. MATERIALS AND METHODS: We retrospectively reviewed the clinical and radiological records of all patients with PRES admitted at our tertiary care medical center from 2007 to 2014. They were divided based their modified Rankin Score at discharge and compared for their baseline variables, clinical, laboratory and imaging features. Poor outcome was defined by a modified Rankin scale 2-6 and was subdivided based on the primary mechanism that led to poor outcome. RESULTS: Out of 100 PRES subjects, 36% had poor discharge outcomes. Factors associated with poor outcomes on univariate analysis were history of diabetes mellitus, coma, high Charlson comorbidity index, post-transplantation, autoimmune condition, lack of systolic or diastolic hypertension, elevated blood urea nitrogen and involvement of the corpus callosum. On multivariate analysis, only prior diabetes mellitus odd ratio (OR) = 6.8 (95% CI 1.1-42.1, p = 0.04), corpus callosum involvement (OR = 11.7; 95% CI 2.4-57.4, p = 0.00) were associated with poor outcome. Poor outcome also correlated with increased length of hospital stay (OR = 7.9; 95% CI 1.3-49.7, p = 0.03). CONCLUSION: Large prospective studies incorporating serial blood glucose values and advanced imaging studies are required to validate these findings. PMID- 26892842 TI - Short-term diagnostic stability of probable headache disorders based on the International Classification of Headache Disorders, 3rd edition beta version, in first-visit patients: a multicenter follow-up study. AB - BACKGROUND: A "Probable headache disorder" is diagnosed when a patient's headache fulfills all but one criterion of a headache disorder in the 3rd beta edition of the International Classification of Headache Disorder (ICHD-3beta). We investigated diagnostic changes in probable headache disorders in first-visit patients after at least 3 months of follow-up. METHODS: This was a longitudinal study using a prospective headache registry from nine headache clinics of referral hospitals. The diagnostic change of probable headache disorders at baseline was assessed at least 3 months after the initial visit using ICHD-3beta. RESULTS: Of 216 patients with probable headache disorders at baseline, the initial probable diagnosis remained unchanged for 162 (75.0 %) patients, while it progressed to a definite diagnosis within the same headache subtype for 45 (20.8 %) by fulfilling the criteria during a median follow-up period of 6.5 months. Significant difference on the proportions of constant diagnosis was not found between headache subtypes (P < 0.935): 75.9 % for probable migraine, 73.7 % for probable tension-type headache (TTH), and 76.0 % for probable other primary headache disorders (OPHD). Among patients with headache recurrence, the proportion of constant diagnosis was higher for probable migraine than for probable TTH plus probable OPHD (59.2 vs. 23.1 %; P < 0.001). The proportions of constant diagnosis did not significantly differ by follow-up duration (>3 and <= 6 months vs. > 6 and <= 10 months) in probable migraine, probable TTH, and probable OPHD, respectively. CONCLUSIONS: In this study, a probable headache diagnosis, based on ICHD-3beta, remained in approximately three-quarters of the outpatients; however, diagnostic stability could differ by headache recurrence and subtype. Probable headache management might have to consider these differences. PMID- 26892844 TI - Early Indication of Decompensated Heart Failure in Patients on Home Telemonitoring: A Comparison of Prediction Algorithms Based on Daily Weight and Noninvasive Transthoracic Bio-impedance. AB - BACKGROUND: Heart Failure (HF) is a common reason for hospitalization. Admissions might be prevented by early detection of and intervention for decompensation. Conventionally, changes in weight, a possible measure of fluid accumulation, have been used to detect deterioration. Transthoracic impedance may be a more sensitive and accurate measure of fluid accumulation. OBJECTIVE: In this study, we review previously proposed predictive algorithms using body weight and noninvasive transthoracic bio-impedance (NITTI) to predict HF decompensations. METHODS: We monitored 91 patients with chronic HF for an average of 10 months using a weight scale and a wearable bio-impedance vest. Three algorithms were tested using either simple rule-of-thumb differences (RoT), moving averages (MACD), or cumulative sums (CUSUM). RESULTS: Algorithms using NITTI in the 2 weeks preceding decompensation predicted events (P<.001); however, using weight alone did not. Cross-validation showed that NITTI improved sensitivity of all algorithms tested and that trend algorithms provided the best performance for either measurement (Weight-MACD: 33%, NITTI-CUSUM: 60%) in contrast to the simpler rules-of-thumb (Weight-RoT: 20%, NITTI-RoT: 33%) as proposed in HF guidelines. CONCLUSIONS: NITTI measurements decrease before decompensations, and combined with trend algorithms, improve the detection of HF decompensation over current guideline rules; however, many alerts are not associated with clinically overt decompensation. PMID- 26892845 TI - Dabigatran Versus Warfarin After Bioprosthesis Valve Replacement for the Management of Atrial Fibrillation Postoperatively: DAWA Pilot Study. AB - OBJECTIVES: Dabigatran is a direct thrombin inhibitor shown to be an effective alternative to warfarin in patients with non-valvular atrial fibrillation (AF). We evaluated the use of dabigatran in patients with bioprosthetic mitral and/or aortic valve replacement and AF. METHODS: We selected 34 and randomized 27 patients in a 1:1 ratio to receive dabigatran or warfarin. The primary endpoint was the presence of a new intracardiac thrombus at 90 days, by transesophageal echocardiogram (TEE). Secondary endpoints included the development of dense spontaneous echo contrast (SEC) and incidence of stroke (ischemic or hemorrhagic), myocardium infarction, valve thrombosis and peripheral embolic events. RESULTS: The trial was terminated prematurely because of low enrollment. There were 27 patients in total: 15 patients placed in the dabigatran group and 12 in the warfarin group. After 90 days, one patient (8.3 %) in the warfarin group and none in the dabigatran group had developed a new intracardiac thrombus. In the dabigatran group, two patients (13.3 %) developed dense SEC versus one patient (8.3 %) in the warfarin group. In the warfarin group, one patient (8.3 %) presented ischemic stroke, and none did in the dabigatran group. We observed no cases of hemorrhagic stroke, valve thrombosis, embolic events or myocardial infarction in either group throughout the study. However, one patient (6.7 %) in the dabigatran group had a fully recovered transient ischemic attack and one patient in the warfarin group died of heart failure. CONCLUSIONS: The use of dabigatran appears to be similar to warfarin in preventing the formation of intracardiac thrombus. TRIAL REGISTRATION: Clinicaltrials.gov NCT01868243. PMID- 26892846 TI - Relationship between white matter integrity and serum cortisol levels in drug naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics. AB - BACKGROUND: Higher daytime cortisol levels because of a hyperactive hypothalamic pituitary-adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts. AIMS: To evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method. METHOD: The MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement. RESULTS: Compared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected). CONCLUSIONS: Our findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal-subcortical and frontal-limbic circuits. PMID- 26892847 TI - Discontinuation of antidepressant medication after mindfulness-based cognitive therapy for recurrent depression: randomised controlled non-inferiority trial. AB - BACKGROUND: Mindfulness-based cognitive therapy (MBCT) and maintenance antidepressant medication (mADM) both reduce the risk of relapse in recurrent depression, but their combination has not been studied. AIMS: To investigate whether MBCT with discontinuation of mADM is non-inferior to MBCT+mADM. METHOD: A multicentre randomised controlled non-inferiority trial (ClinicalTrials.gov:NCT00928980). Adults with recurrent depression in remission, using mADM for 6 months or longer (n= 249), were randomly allocated to either discontinue (n= 128) or continue (n= 121) mADM after MBCT. The primary outcome was depressive relapse/recurrence within 15 months. A confidence interval approach with a margin of 25% was used to test non-inferiority. Key secondary outcomes were time to relapse/recurrence and depression severity. RESULTS: The difference in relapse/recurrence rates exceeded the non-inferiority margin and time to relapse/recurrence was significantly shorter after discontinuation of mADM. There were only minor differences in depression severity. CONCLUSIONS: Our findings suggest an increased risk of relapse/recurrence in patients withdrawing from mADM after MBCT. PMID- 26892848 TI - Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate. AB - BACKGROUND: Controversy exists over antidepressant use in bipolar II depression. AIMS: To compare the safety and effectiveness of antidepressantv.mood stabiliser monotherapy for bipolar type II major depressive episodes. METHOD: Randomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n= 65)v.lithium (n= 64) monotherapy in adult out-patients (trial registration numberNCT00602537). RESULTS: Primary outcome - venlafaxine produced a greater response rate (67.7%)v lithium (34.4%,P<0.001). Secondary outcomes - venlafaxine produced a greater remission rate (58.5%v 28.1%,P<0.001); greater decline in depression symptom scores over time (beta = -5.32, s.e. = 1.16, chi(2)= 21.19,P<0.001); greater reduction in global severity scores over time (beta = -1.05, s.e. = 0.22, w(2)= 22.33,P<0.001); and greater improvement in global change scores (beta = -1.31, s.e. = 0.32, chi(2)= 16.95,P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments. CONCLUSIONS: These findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium. PMID- 26892849 TI - Eye movement desensitisation and reprocessing therapy v. stabilisation as usual for refugees: randomised controlled trial. AB - BACKGROUND: Eye movement desensitisation and reprocessing (EMDR) therapy is a first-line treatment for adults with post-traumatic stress disorder (PTSD). Some clinicians argue that with refugees, directly targeting traumatic memories through EMDR may be harmful or ineffective. AIMS: To determine the safety and efficacy of EMDR in adult refugees with PTSD (trial registration: ISRCTN20310201). METHOD: In total, 72 refugees referred for specialised treatment were randomly assigned to 12 h of EMDR (3*60 min planning/preparation followed by 6*90 min desensitisation/reprocessing) or 12 h (12*60 min) of stabilisation. The Clinician-Administered PTSD Scale (CAPS) and Harvard Trauma Questionnaire (HTQ) were primary outcome measures. RESULTS: Intention-to-treat analyses found no differences in safety (one severe adverse event in the stabilisation condition only) or efficacy (effect sizes: CAPS -0.04 and HTQ 0.20) between the two conditions. CONCLUSIONS: Directly targeting traumatic memories through 12 h of EMDR in refugee patients needing specialised treatment is safe, but is only of limited efficacy. PMID- 26892850 TI - Risk of depressive disorder following disasters and military deployment: systematic review with meta-analysis. AB - BACKGROUND: Numerous studies describe the occurrence of post-traumatic stress disorder following disasters, but less is known about the risk of major depression. AIMS: To review the risk of depressive disorder in people surviving disasters and in soldiers returning from military deployment. METHOD: A systematic literature search combined with reference screening identified 23 controlled epidemiological studies. We used random effects models to compute pooled odds ratios (ORs). RESULTS: The average OR was significantly elevated following all types of exposures: natural disaster OR = 2.28 (95% CI 1.30-3.98), technological disaster OR = 1.44 (95% CI 1.21-1.70), terrorist acts OR = 1.80 (95% CI 1.38-2.34) and military combat OR = 1.60 (95% CI 1.09-2.35). In a subset of ten high-quality studies OR was 1.41 (95% CI 1.06-1.87). CONCLUSIONS: Disasters and combat experience substantially increase the risk of depression. Whether psychological trauma per se or bereavement is on the causal path is unresolved. PMID- 26892851 TI - Changes in extra-striatal functional connectivity in patients with schizophrenia in a psychotic episode. AB - BACKGROUND: In patients with schizophrenia in a psychotic episode, intra-striatal intrinsic connectivity is increased in the putamen but not ventral striatum. Furthermore, multimodal changes have been observed in the anterior insula that interact extensively with the putamen. AIMS: We hypothesised that during psychosis, putamen extra-striatal functional connectivity is altered with both the anterior insula and areas normally connected with the ventral striatum (i.e. altered functional connectivity distinctiveness of putamen and ventral striatum). METHOD: We acquired resting-state functional magnetic resonance images from 21 patients with schizophrenia in a psychotic episode and 42 controls. RESULTS: Patients had decreased functional connectivity: the putamen with right anterior insula and dorsal prefrontal cortex, the ventral striatum with left anterior insula. Decreased functional connectivity between putamen and right anterior insula was specifically associated with patients' hallucinations. Functional connectivity distinctiveness was impaired only for the putamen. CONCLUSIONS: Results indicate aberrant extra-striatal connectivity during psychosis and a relationship between reduced putamen-right anterior insula connectivity and hallucinations. Data suggest that altered intrinsic connectivity links striatal and insular pathophysiology in psychosis. PMID- 26892853 TI - Shoulder Pain After Definitive Lung Radiotherapy. PMID- 26892852 TI - Association between physical performance and cardiovascular events in patients with coronary artery disease: protocol for a meta-analysis. AB - BACKGROUND: Physical performance such as muscle strength or walking speed of patients with coronary artery disease (CAD) is lower than that of people who do not have CAD and is related to mortality and re-admission rates. Recent studies have shown that skeletal muscle strength, such as grip strength, was closely associated with cardiac events. Physical performance testing is quick, safe, and inexpensive and provides a reliable assessment tool for routine clinical practice. The aim of this meta-analysis is to clarify the association between physical performance testing and the risk of cardiovascular events and mortality. METHODS/DESIGN: This meta-analysis will include male and female participants of any age in community settings who have a history of the following conditions or procedures: myocardial infarction, or coronary revascularization (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or coronary artery stent), angina pectoris, heart failure, heart transplant, or coronary artery disease defined by angiography. We will search EMBASE and MEDLINE, PubMed, and the Cochrane Library with no limitations on date, language, document type, or publication status. Identified studies will be prospective and retrospective cohort studies. Physical performance will be defined as upper extremity strength, lower extremity strength, walking speed, or other performance scale. Six review authors will independently extract study characteristics from included studies. Participants will be divided into subgroups according to age (middle-aged <65 years and elderly >= 65 years), diagnosis (coronary artery disease and heart failure) and follow-up time (up to 12 months and over 12 months). We will pool hazard ratios of Cox proportional hazard models after logarithmic transformation and perform the meta-analysis by using inverse-variance method. DISCUSSION: To our knowledge, this meta-analysis will be the first report to assess the association between physical performance and cardiovascular events in CAD patients. We hope that these findings may help to estimate the prognosis for CAD patients in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015020886. PMID- 26892854 TI - Electrophysiological evidence for flexible goal-directed cue processing during episodic retrieval. AB - A widely held assumption is that memory retrieval is aided by cognitive control processes that are engaged flexibly in service of memory retrieval and memory decisions. While there is some empirical support for this view, a notable exception is the absence of evidence for the flexible use of retrieval control in functional neuroimaging experiments requiring frequent switches between tasks with different cognitive demands. This absence is troublesome in so far as frequent switches between tasks mimic some of the challenges that are typically placed on memory outside the laboratory. In this experiment we instructed participants to alternate frequently between three episodic memory tasks requiring item recognition or retrieval of one of two different kinds of contextual information encoded in a prior study phase (screen location or encoding task). Event-related potentials (ERPs) elicited by unstudied items in the two tasks requiring retrieval of study context were reliably different, demonstrating for the first time that ERPs index task-specific processing of retrieval cues when retrieval goals change frequently. The inclusion of the item recognition task was a novel and important addition in this study, because only the ERPs elicited by unstudied items in one of the two context conditions diverged from those in the item recognition condition. This outcome constrains functional interpretations of the differences that emerged between the two context conditions and emphasises the utility of this baseline in functional imaging studies of retrieval processing operations. PMID- 26892855 TI - Mapping the self in the brain's default mode network. AB - The brain's default mode network (DMN) has become closely associated with self referential mental activity, particularly in the resting-state. While the DMN is important for such processes, it has functions other than self-reference, and self-referential processes are supported by regions outside of the DMN. In our study of 88 participants, we examined self-referential and resting-state processes to clarify the extent to which DMN activity was common and distinct between the conditions. Within areas commonly activated by self-reference and rest we sought to identify those that showed additional functional specialization for self-referential processes: these being not only activated by self-reference and rest but also showing increased activity in self-reference versus rest. We examined the neural network properties of the identified 'core-self' DMN regions in medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and inferior parietal lobule-using dynamic causal modeling. The optimal model identified was one in which self-related processes were driven via PCC activity and moderated by the regulatory influences of MPFC. We thus confirm the significance of these regions for self-related processes and extend our understanding of their functionally specialized roles. PMID- 26892857 TI - Perception of actions performed by external agents presupposes knowledge about the relationship between action and effect. AB - We used the (14)C-deoxyglucose method to reveal changes in activity, in the lateral sulcus of monkeys, elicited by reaching-to-grasp in the light or in the dark and by observation of the same action executed by an external agent. Both visually-guided execution and observation of the same action activated the secondary somatosensory cortex, the ventral somatosensory area, the somatorecipient parietal ventral area, the retroinsula and the caudo-medial area of the auditory belt. These matching activations indicate that the somesthetic consequences of movements, generated bottom-up during action execution, may also be triggered top-down during action observation to represent the predicted sensory consequences of the perceived movement. The posterior granular part of insula found to be activated only for action execution and its anterior agranular part activated only for action observation may contribute to the attribution of action to the correct agent. Also, execution in the dark implicated all components activated by execution in the light but the retroinsula. In conclusion, activation of the somatorecipient parietal areas, not only for action execution but also for action-observation, indicates that perception of actions performed by an external agent presupposes knowledge about the action-effect relationships, and that understanding others' actions consists of running off line previously stored sensory-motor programs. PMID- 26892856 TI - Look into my eyes: Investigating joint attention using interactive eye-tracking and fMRI in a developmental sample. AB - Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self initiated JA specifically activated areas related to social cognition, decision making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects. PMID- 26892858 TI - Hand gestures as visual prosody: BOLD responses to audio-visual alignment are modulated by the communicative nature of the stimuli. AB - During public addresses, speakers accompany their discourse with spontaneous hand gestures (beats) that are tightly synchronized with the prosodic contour of the discourse. It has been proposed that speech and beat gestures originate from a common underlying linguistic process whereby both speech prosody and beats serve to emphasize relevant information. We hypothesized that breaking the consistency between beats and prosody by temporal desynchronization, would modulate activity of brain areas sensitive to speech-gesture integration. To this aim, we measured BOLD responses as participants watched a natural discourse where the speaker used beat gestures. In order to identify brain areas specifically involved in processing hand gestures with communicative intention, beat synchrony was evaluated against arbitrary visual cues bearing equivalent rhythmic and spatial properties as the gestures. Our results revealed that left MTG and IFG were specifically sensitive to speech synchronized with beats, compared to the arbitrary vision-speech pairing. Our results suggest that listeners confer beats a function of visual prosody, complementary to the prosodic structure of speech. We conclude that the emphasizing function of beat gestures in speech perception is instantiated through a specialized brain network sensitive to the communicative intent conveyed by a speaker with his/her hands. PMID- 26892859 TI - Criticism hurts everybody, praise only some: Common and specific neural responses to approving and disapproving social-evaluative videos. AB - Social evaluation is a ubiquitous feature of daily interpersonal interactions and can produce strong positive or negative emotional reactions. While previous research has highlighted neural correlates of static or dynamic facial expressions, little is known about neural processing of more naturalistic social interaction simulations or the modulating role of inter-individual differences such as trait fear of negative/positive evaluation. The present fMRI study investigated neural activity of 37 (21 female) healthy participants while watching videos of posers expressing a range of positive, negative, and neutral statements tapping into several basic and social emotions. Unpleasantness ratings linearly increased in response to positive to neutral to negative videos whereas arousal ratings were elevated in both emotional video conditions. At the whole brain level, medial prefrontal and rostral anterior cingulate cortex activated strongly in both emotional conditions which may be attributed to the cognitive processing demands of responding to complex social evaluation. Region of interest analysis for basic emotion processing areas revealed enhanced amygdala activation in both emotional conditions, whereas anterior and posterior insula showed stronger activity during negative evaluations only. Individuals with high fear of positive evaluation were characterized by increased posterior insula activity during positive videos, suggesting heightened interoception. Taken together, these results replicate and extend studies that used facial expression stimuli and reveal neurobiological systems involved in processing of more complex social evaluative videos. Results also point to vulnerability factors for social interaction related psychopathologies. PMID- 26892860 TI - Competing against a familiar friend: Interactive mechanism of the temporo parietal junction with the reward-related regions during episodic encoding. AB - Competition enhances learning under certain circumstances. However, little is known about how the neural mechanisms involved in a competition during the episodic encoding are modulated by the social distance of personal relationships with opponents. To investigate this issue, using functional magnetic resonance imaging (fMRI), we scanned healthy young adults during a competition with their familiar friends and unfamiliar others in the episodic encoding. Three major findings emerged from this study. First, activations in the right temporo parietal junction (rTPJ) were significantly greater in the competition with familiar friends than with unfamiliar others, and the activations in this region were significantly correlated with the subjective ratings of motivation. Second, striatum and amygdala activations increased by the competition with familiar friends were significantly correlated with the increased ratings of pleasantness, which reflected emotionally positive feelings in victory for the competition with familiar opponents. Third, the functional connectivity between the rTPJ and reward-related regions, including the striatum and substantia nigra, was higher in the competition with familiar friends than with unfamiliar others. Taken together with our behavioral findings, in which memories encoded by competing with familiar friends were remembered more accurately than those with unfamiliar others, the interacting mechanisms between the rTPJ that is involved in social motivation and the reward-related regions that are involved in social reward could contribute to the enhancement of memories encoded in the competition with familiar others. PMID- 26892861 TI - How do negative emotions impair self-control? A neural model of negative urgency. AB - Self-control often fails when people experience negative emotions. Negative urgency represents the dispositional tendency to experience such self-control failure in response to negative affect. Neither the neural underpinnings of negative urgency nor the more general phenomenon of self-control failure in response to negative emotions are fully understood. Previous theorizing suggests that an insufficient, inhibitory response from the prefrontal cortex may be the culprit behind such self-control failure. However, we entertained an alternative hypothesis: negative emotions lead to self-control failure because they excessively tax inhibitory regions of the prefrontal cortex. Using fMRI, we compared the neural activity of people high in negative urgency with controls on an emotional, inhibitory Go/No-Go task. While experiencing negative (but not positive or neutral) emotions, participants high in negative urgency showed greater recruitment of inhibitory brain regions than controls. Suggesting a compensatory function, inhibitory accuracy among participants high in negative urgency was associated with greater prefrontal recruitment. Greater activity in the anterior insula on negatively-valenced, inhibitory trials predicted greater substance abuse one month and one year after the MRI scan among individuals high in negative urgency. These results suggest that, among people whose negative emotions often lead to self-control failure, excessive reactivity of the brain's regulatory resources may be the culprit. PMID- 26892863 TI - Rare emergence of drug resistance in HIV-1 treatment-naive patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. AB - Tenofovir alafenamide (TAF), a novel prodrug of the NtRTI tenofovir (TFV), delivers TFV-diphosphate (TFV-DP) to target cells more efficiently than the current prodrug, tenofovir disoproxil fumarate (TDF), with a 90% reduction in TFV plasma exposure. TAF, within the fixed dose combination of elvitegravir /cobicistat / emtricitabine (FTC)/TAF (E/C/F/TAF), has been evaluated in one Phase 2 and two Phase 3 randomized, double-blinded studies in HIV-infected treatment-naive patients, comparing E/C/F/TAF to E/C/F/TDF. In these studies, the TAF-containing group demonstrated non-inferior efficacy to the TDF-containing comparator group with 91.9% of E/C/F/TAF patients having <50 copies/mL of HIV-1 RNA at week 48. An integrated resistance analysis across these three studies was conducted, including HIV-1 genotypic analysis at screening, and genotypic/phenotypic analysis for patients with HIV-1 RNA>400 copies/mL at virologic failure. Pre-existing primary resistance-associated mutations (RAMs) were observed at screening among the 1903 randomized and treated patients: 7.5% had NRTI-RAMs, 18.2% had NNRTI-RAMs, and 3.4% had primary PI-RAMs. Pre-treatment RAMs did not influence treatment response at Week 48. In the E/C/F/TAF group, resistance development was rare; seven patients (0.7%, 7/978) developed NRTI RAMs, five of whom (0.5%, 5/978) also developed primary INSTI-RAMs. In the E/C/F/TDF group, resistance development was also rare; seven patients (0.8%, 7/925) developed NRTI-RAMs, four of whom (0.4%, 4/925) also developed primary INSTI-RAMs. An additional analysis by deep sequencing in virologic failures revealed minimal differences compared to population sequencing. Overall, resistance development was rare in E/C/F/TAF-treated patients, and the pattern of emergent mutations was similar to E/C/F/TDF. PMID- 26892866 TI - Colonoscopy and chromoscopy in hereditary colorectal cancer syndromes. AB - With hereditary colorectal cancer prevention studies it is difficult to demonstrate reduced mortality. Large populations are needed with well characterized genetics followed over a long period of time. Those studies do exist for standard white light colonoscopy surveillance in Lynch syndrome, but not for newer technologies including chromoscopy. For these newer technologies adenoma detection rate becomes the stand-in for mortality, and the assumption is made that surveillance efficacy impacts cancer occurrence. Though well-designed and important work exists in this area, the data do not support firm conclusions regarding the use of chromoscopy in Lynch syndrome. PMID- 26892867 TI - Effects of Partial Sleep Deprivation on Information Processing Speed in Adolescence. AB - OBJECTIVES: Although chronic sleep loss is highly common among teens, few objective sleep studies have examined its effects on cognitive performance, and specifically on information processing speed (IPS), a measure of cognitive proficiency. METHODS: Forty-five adolescents underwent four consecutive nights of monitored sleep restriction (6-6.5 hr/night) and four nights of sleep extension (10-10.5 hr/night), in counterbalanced order, and separated by a washout period. Following each sleep period, cognitive performance was assessed, at a fixed morning time, using a computerized neuropsychological battery including an IPS task, a timed test providing both accuracy and reaction time outcome measures. RESULTS: Overall IPS performance was poorer in the restricted when compared to the extended condition. Increasing task load and pace were associated with increased accuracy for both sleep conditions. However, a significant pace by load interaction effect was only found in the extended condition, with post hoc tests showing that for medium and hard loads, IPS accuracies were better with increasing pace of task. Differences in IPS reaction times were not found between the sleep conditions. In addition, sleep-related changes in IPS indices were correlated with changes in executive function, motor skill, and attention performance. CONCLUSIONS: Adolescents' ability to process information may be especially vulnerable to sleep loss. Under ideal sleep conditions, however, they seem to be able to achieve optimal performance, particularly on more challenging problems. The functional implications of these findings may be particularly relevant to teens, who are often sleep deprived and are constantly required to process academic, social, and emotional input. PMID- 26892862 TI - Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers. AB - Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called 'exosomes', which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID- 26892865 TI - Familial atypical multiple mole melanoma (FAMMM) syndrome: history, genetics, and heterogeneity. AB - Approximately 5-10 % of cutaneous melanoma occurs in kindreds with a hereditary predisposition. Mutations in the CDKN2A gene are found to occur in approximately 20-40 % of these kindreds. The first historical mention of what is now called the familial atypical multiple mole melanoma syndrome appears to be from 1820, with more reports throughout the 1950s, 1960s, and later years. In 1991, Lynch and Fusaro described an association between familial multiple mole melanoma and pancreatic cancer and work continues to elucidate the syndrome's genotypic and phenotypic heterogeneity. Individuals at risk for familial melanoma need periodic screenings. Unfortunately, adequate screening for pancreatic cancer does not currently exist, but pancreatic cancer's prominence in the hereditary setting will hopefully act as a stimulus for development of novel screening measures. PMID- 26892864 TI - SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer. AB - An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-beta signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well. PMID- 26892869 TI - Survey and first molecular characterization of Echinococcus granulosus sensu stricto (G1) in Pampas fox (Lycalopex gymnocercus) in Buenos Aires province, Argentina. AB - Echinococcosis is a zoonosis caused by tapeworms of the genus Echinococcus. Echinococcus granulosus sensu lato (s. l.) has a world-wide distribution and its transmission is primarily maintained in a synanthropic cycle with dogs as definitive hosts and livestock species as intermediate hosts. However, many wild canids also function as definitive hosts for E. granulosus s. l. Echinococcosis in humans is mainly caused by E. granulosus sensu stricto (s. s.) G1 genotype. In the present work, we expanded the epidemiological study on echinococcosis reported cases in Pampas fox (Lycalopex gymnocercus) to provide a prevalence estimate for rural areas of southern Buenos Aires province, Argentina. Ninety five whole intestines were analyzed using the sedimentation and counting technique with a result of 83 foxes (87.37%) harboring at least one helminth species. E. granulosus s. l. adults were found in one Pampas fox (1.05%). These adult helminthes were E. granulosus s. s. (G1) according to the genotyping analysis of a 450-bp region of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. PMID- 26892868 TI - Characterization of a natural triple-tandem c-di-GMP riboswitch and application of the riboswitch-based dual-fluorescence reporter. AB - c-di-GMP riboswitches are structured RNAs located in the 5'-untranslated regions (5'-UTRs) of mRNAs that regulate expression of downstream genes in response to changing concentrations of the second messenger c-di-GMP. We discovered three complete c-di-GMP riboswitches (Bc3, Bc4 and Bc5 RNA) with similar structures, which are arranged in tandem to constitute a triple-tandem (Bc3-5 RNA) riboswitch in the 5'-UTR of the cspABCDE mRNA in Bacillus thuringiensis subsp. chinensis CT 43. Our results showed that this natural triple-tandem riboswitch controlled the expression of the reporter gene more stringently and digitally than the double tandem or single riboswitch. A sandwich-like dual-fluorescence reporter was further constructed by fusing the Bc3-5 RNA gene between the two fluorescence protein genes amcyan and turborfp. This reporter strain was found to exhibit detectable fluorescence color changes under bright field in response to intracellular c-di-GMP level altered by induced expression of diguanylate cyclase (DGC) PleD. Using this system, two putative membrane-bound DGCs from B. thuringiensis and Xanthomonas oryzae were verified to be functional by replacing pleD with the corresponding DGC genes. This report represented the first native triple-tandem riboswitch that was applied to serve as a riboswitch-based dual fluorescence reporter for the efficient and convenient verification of putative DGC activity in vivo. PMID- 26892870 TI - Ultrasonographic findings of small lesion of hepatic alveolar echinococcosis. AB - OBJECTIVE: To investigate the features of small lesions of hepatic alveolar echinococcsis paragonimiasis (AE) on conventional ultrasound (US) and contrast enhanced ultrasound (CEUS) imaging. METHODS: This retrospective study was approved by the Institutional Review Board, and the requirement for informed consent was waived. US and CEUS features of seventeen lesions histopathologically proven hepatic AE were retrospectively reviewed. Nine patients with seventeen hepatic AE lesions who were admitted to our hospital between January 2008 and June 2015 were enrolled. All hepatic AE lesions were small (<=3cm). The US and CEUS examinations were performed with a Philips IU22 scanner with a 1-5-MHz convex transducer. After US was completed, the CEUS study was performed. Pulse inversion harmonic imaging was used for CEUS. A bolus injection of 2.4mL of a sulfur-hexafluoride-filled microbubble contrast agent (SonoVue) was administered. The features of the lesions by US and CEUS were retrospectively reviewed. RESULTS: In total, all lesions were detected by US and CEUS. The mean size of the lesions was 1.8+/-0.7cm (range: 1.0-3.0cm). Five patients (55.6%, 5/9) had a lesion in the right hepatic lobe; two (22.2%, 2/9) had two lesions in the left hepatic lobe; and two patients (22.2%, 2/9) had four lesions in the right lobe. Seven lesions (41.2%, 7/17) were hypoechoic nodules and ten (58.8%, 10/17) were hyperechoic nodules. Nine lesions (52.3%, 9/17) were of mixed echogenicity type. Ten lesions (58.8%, 10/17) had a regular shape. Nine lesions (52.3%, 9/27) had a sharp margin and six (35.3%, 6/17) had indistinct margins. Four lesions (57.1%, 4/7) with hypoechoic nodule had small dotted calcifications, none was found in hyperechoic nodule. Seven nodules (41.2%, 7/17) showed short striated blood-flow signals surrounding the margin, on color Doppler flow imaging. By CEUS, All the lesions were hypoechoic with mixed content (). 12 lesions (70.1%, 12/17) were rim enhanced with irregular piece-like nonenhanced internal areas and showed nonhomogeneous hypo-enhancement during the arterial phase, with mixed echogenicity. The main pathological findings included: (1) (1) coagulative or liquefactive necrosis within the lesion with sporadic distribution of wizened alveolar hydatid cysts; and (2) hyperplasia of granulomatous and fibrous tissue around the lesion. CONCLUSION: Hyperechogenicity, mixed echogenicity type, dotted calcification with hypoechogenicity, sharp margin, rim enhancement and piece-like nonenhanced areas could be seen as the main ultrasonographic features of small lesion of hepatic alveolar echinococcosis. PMID- 26892871 TI - The forgotten people in British public health: a national neglect of the dying, bereaved and caregivers. AB - The clinical and social epidemiology of living with a life-threatening or life limiting illness, frail ageing, long-term caregiving, and grief and bereavement is well documented in the palliative care, psycho-oncology and psychiatric literature but this investigation asks what interest exists from the mainstream public health sector in these health and illness experiences. This paper reports a content analysis of 7 key British public health journals, 14 major public health textbooks and 3 public health websites employing key word and synonym searches to assess the size and quality of interest in populations related to ageing, dying, caregiving, and grief and bereavement. Compared with other public health issues, such as obesity and tobacco use, for examples, interest in the social experience and epidemiology of end-of-life experiences is extremely low. Reasons for this lack of interest are explored. PMID- 26892872 TI - Set one standard and do not change it. PMID- 26892873 TI - Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function. AB - BACKGROUND: The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. METHODS: This study investigates the effects of bacterial sepsis and chronic inflammation on muscle fiber type, local TH metabolism, and mitochondrial function in the diaphragm. Two mouse models were used: sepsis induced by S. pneumoniae infection or chronic inflammation induced by subcutaneous turpentine injection. In vitro, the effect of bacterial endotoxin (LPS) on mitochondrial function in C2C12 myotubes was studied. RESULTS: Sepsis induced a transient increase in the fiber type I profile and increased Dio3 expression while decreasing Dio2, Thra1, and Slc16a2 expression. Triiodothyronine positively regulated genes Tnni2 and Myog were decreased, indicating reduced TH signaling in the diaphragm. In contrast, chronic inflammation increased the fiber type II profile in the diaphragm as well as Thra1, Thrb1, and Myog expression while decreasing Dio3 expression, suggesting increased TH responsiveness during chronic inflammation. LPS-stimulated C2C12 myotubes showed decreased Dio2 expression and reduced basal oxygen consumption as well as non-mitochondrial respiration. The same respiratory profile was induced by Dio2 knockdown in myotubes. CONCLUSIONS: The in vivo results show differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, TH metabolism, and mitochondrial function, while the in vitro results point to a causal role for altered TH metabolism in functional muscle impairment. These findings may be relevant for the pathogenesis of impaired respiratory function in critical illness. PMID- 26892875 TI - Sharp decline of malaria cases in the Burie Zuria, Dembia, and Mecha districts, Amhara Region, Ethiopia, 2012-2014: descriptive analysis of surveillance data. AB - BACKGROUND: In the Amhara Region of Ethiopia, a steep decline of malaria cases was seen in early 2014. This study verified the decrease of the malaria cases along with the positivity rates among acute febrile illness patients, from late 2012 through 2014 in selected districts of the Amhara Region of Federal Republic of Ethiopia. METHODS: Descriptive epidemiological analysis was conducted on the routine malaria surveillance data from the World Health Organization epidemiological week 28 of 2012 to week 52 of 2014 in three districts: Burie Zuria, Dembia and Mecha, the Amhara Region in Ethiopia. The authors visited the three district health offices, and health centres, when necessary, and collected the surveillance data on malaria for that period. RESULTS: The study found that the malaria cases, along with the positivity rates, decreased from late 2012 to early 2014 in all three districts. Though the situation had slightly reverted in late 2014, the numbers of cases were much smaller than in late 2012 in all three districts. Despite the different diagnostic techniques used at health centres (malaria microscopy) and health posts (rapid diagnostic tests), moderate to high correlations were found, suggesting that the trends were real and not caused by a defect in the reagent, differences in the technicians' skills for microscopy, or a change of the health workers' attitudes toward cases with acute febrile illness. The decrease in malaria cases in early 2014 may have resulted from successful implementation of the three pillars of malaria control-case management, indoor residual spraying and insecticide-treated nets-in the districts where a high percentage of households were protected by indoor residual spraying and/or insecticide-treated nets. CONCLUSION: While the current efforts for malaria control should be strengthened and maintained, the review of malaria surveillance data should also be used to verify the malaria trend in the region. PMID- 26892874 TI - An MRI-based classification scheme to predict passive access of 5 to 50-nm large nanoparticles to tumors. AB - Nanoparticles are useful tools in oncology because of their capacity to passively accumulate in tumors in particular via the enhanced permeability and retention (EPR) effect. However, the importance and reliability of this effect remains controversial and quite often unpredictable. In this preclinical study, we used optical imaging to detect the accumulation of three types of fluorescent nanoparticles in eight different subcutaneous and orthotopic tumor models, and dynamic contrast-enhanced and vessel size index Magnetic Resonance Imaging (MRI) to measure the functional parameters of these tumors. The results demonstrate that the permeability and blood volume fraction determined by MRI are useful parameters for predicting the capacity of a tumor to accumulate nanoparticles. Translated to a clinical situation, this strategy could help anticipate the EPR effect of a particular tumor and thus its accessibility to nanomedicines. PMID- 26892877 TI - Brain inflammation, neurodegeneration and seizure development following picornavirus infection markedly differ among virus and mouse strains and substrains. AB - Infections, particularly those caused by viruses, are among the main causes of acquired epilepsy, but the mechanisms causing epileptogenesis are only poorly understood. As a consequence, no treatment exists for preventing epilepsy in patients at risk. Animal models are useful to study epileptogenesis after virus induced encephalitis and how to interfere with this process, but most viruses that cause encephalitis in rodents are associated with high mortality, so that the processes leading to epilepsy cannot be investigated. Recently, intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6 (B6) mice was reported to induce early seizures and epilepsy and it was proposed that the TMEV mouse model represents the first virus infection-driven animal model of epilepsy. In the present study, we characterized this model in two B6 substrains and seizure-resistant SJL/J mice by using three TMEV (sub)strains (BeAn-1, BeAn 2, DA). The idea behind this approach was to study what is and what is not necessary for development of acute and late seizures after brain infection in mice. Receiver operating characteristic (ROC) curve analysis was used to determine which virus-induced brain alterations are associated with seizure development. In B6 mice infected with different TMEV virus (sub)strains, the severity of hippocampal neurodegeneration, amount of MAC3-positive microglia/macrophages, and expression of the interferon-inducible antiviral effector ISG15 were almost perfect at discriminating seizing from non-seizing B6 mice, whereas T-lymphocyte brain infiltration was not found to be a crucial factor. However, intense microglia/macrophage activation and some hippocampal damage were also observed in SJL/J mice. Overall, the TMEV model provides a unique platform to study virus and host factors in ictogenesis and epileptogenesis. PMID- 26892878 TI - Assessment of home hazards for childhood injuries in an urban population in New Delhi. AB - BACKGROUND: Childhood injuries, especially the unintentional category of injuries, occur most commonly in the environment inside a child's home. The primary objective of the present study was to assess the presence of home hazards for childhood injuries in households in an urban resettlement colony in New Delhi. METHODS: A community-based cross-sectional study was carried out in an urban resettlement colony in Delhi. A hazards assessment tool was used to check the presence of hazards in the houses. RESULTS: A total of 225 households were included. It was seen that121 (53.7%) had a cooking stove within the reach of the child, and 190 (84.3%) had the gas pipe within reach. Fire hazard was seen in 84% of houses. About 78% of households did not have locked storage for chemicals. CONCLUSION: The study revealed a significant burden of hazards for childhood injuries within their own homes, thus emphasizing the need for injury prevention interventions to reduce the number of hazards. PMID- 26892879 TI - Understanding the lived experience of women before and after fistula repair: a qualitative study in Kenya. AB - OBJECTIVE: To gain understanding of the first-hand experience of women prior to and following repair of a vaginal fistula, to determine the most effective support mechanisms. DESIGN: Qualitative phenomenological study using a series of in-depth semi-structured interviews at two time points: prior to fistula repair and 6 months post-surgery. Data were analysed thematically. SETTING: Three fistula clinics in three districts in Kenya. POPULATION: A purposive sample of 16 women suffering with vaginal fistula who were seeking fistula repair. METHODS: Thrity-two semi-structured interviews were conducted. RESULTS: The two main themes represented the women's journeys from social isolation to social reintegration. Women felt euphoric following fistula repair, believing that a 'miracle' had occurred. However, the 'post-miracle phase' demonstrated that the social and psychological impact of fistula leaves scars that are not easily healed, even when fistula repair is successful. CONCLUSION: Women's experiences of living with fistula have an impact beyond that which can be repaired solely by surgery. The findings from this study support the need for more active psychological assessment in the management of women with fistula, and the role of targeted psychological support in any package of care given in the post repair phase. The format of this support requires further study. Engagement by health professionals with the wider community could raise awareness of the causes of fistula, and provide support for significant others who may also be feeling vulnerable. It is likely that the collaborative efforts from health professionals and community members will provide the most effective support. TWEETABLE ABSTRACT: Fistula surgery alone is insufficient for women's physical, social and psychological recovery. PMID- 26892880 TI - The road less travelled: Australian women's experiences with vulval cancer. AB - Despite advances in surgical treatments and the availability of more conservative treatment options, women treated for vulval cancer still experience significant complications such as urinary incontinence, lymphoedema, pruritus, sexual and intimacy issues. These issues can profoundly impact a woman's quality of life. The subjective experience of women diagnosed and treated for vulval cancer in the literature is limited, possibly due to its comparable rarity to other gynaecological and female cancers and because it was traditionally seen mainly in the elderly female population. Nonetheless, younger women are also being diagnosed with vulval cancer. This paper reports the findings from a qualitative study about twelve women's experiences with vulval cancer from diagnosis, through treatment and recovery. Women's feelings of isolation, their unmet information and support needs, physical concerns arising from vulval cancer, particularly after surgery, and the consequences for their body image and intimate relationships with partners, were highlighted within the data. The central findings from this study emphasise the need for further research to develop appropriate interventions for women with vulval cancer. It also highlights opportunities to improve clinical practice into the supportive care of women with this isolating disease. PMID- 26892876 TI - Protective effects of butyrate-based compounds on a mouse model for spinal muscular atrophy. AB - Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analog (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs-glyceryl tributyrate (BA3G) and VX563-on the phenotype of SMNDelta7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNDelta7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNDelta7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3beta, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favorable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID- 26892881 TI - When and Why Is Research without Consent Permissible? AB - The purpose of consent is to let a person waive her rights of control over some aspects of her life. But becoming part of a research study does not always seriously undermine one's control. PMID- 26892882 TI - Enhancing voluntary imitation through attention and motor imagery. AB - Action observation activates brain areas involved in performing the same action and has been shown to increase motor learning, with potential implications for neurorehabilitation. Recent work indicates that the effects of action observation on movement can be increased by motor imagery or by directing attention to observed actions. In voluntary imitation, activation of the motor system during action observation is already increased. We therefore explored whether imitation could be further enhanced by imagery or attention. Healthy participants observed and then immediately imitated videos of human hand movement sequences, while movement kinematics were recorded. Two blocks of trials were completed, and after the first block participants were instructed to imagine performing the observed movement (Imagery group, N = 18) or attend closely to the characteristics of the movement (Attention group, N = 15), or received no further instructions (Control group, N = 17). Kinematics of the imitated movements were modulated by instructions, with both Imagery and Attention groups being closer in duration, peak velocity and amplitude to the observed model compared with controls. These findings show that both attention and motor imagery can increase the accuracy of imitation and have implications for motor learning and rehabilitation. Future work is required to understand the mechanisms by which these two strategies influence imitation accuracy. PMID- 26892883 TI - The effect of 6 h of running on brain activity, mood, and cognitive performance. AB - Long-duration exercise has been linked with the psychological model of flow. It is expected that the flow experience is characterized by specific changes in cortical activity, especially a transient hypofrontality, which has recently been connected with an increase in cognitive performance post-exercise. Nevertheless, data on neuro-affective and neuro-cognitive effects during prolonged exercise are rare. The cognitive performance, mental state, flow experience, and brain cortical activity of 11 ultramarathon runners (6 female, 5 male) were assessed before, several times during, and after a 6-h run. A decrease in cortical activity (beta activity) was measured in the frontal cortex, whereas no changes were measured for global beta, frontal or global alpha activity. Perceived physical relaxation and flow state increased significantly after 1 h of running but decreased during the following 5 h. Perceived physical state and motivational state remained stable during the first hour of running but then decreased significantly. Cognitive performance as well as the underlying neurophysiological events (recorded as event-related potentials) remained stable across the 6-h run. Despite the fact that women reported significant higher levels of flow, no further gender effects were noticeable. Supporting the theory of a transient hypofrontality, a clear decrease in frontal cortex activity was noticeable. Interestingly, this had no effect on cognitive performance. The fact that self reported flow experience only increased during the first hour of running before decreasing, leads us to assume that changes in cortical activity, and the experience of flow may not be linked as previously supposed. PMID- 26892885 TI - Modality dependence and intermodal transfer in the Corsi Spatial Sequence Task: Screen vs. Floor. AB - Four versions of the Corsi Spatial Sequence Task (CSST) were tested in a complete within-subject design, investigating whether participants' performance depends on the modality of task presentation and reproduction that put different demands on spatial processing. Presentation of the sequence (encoding phase) and the reproduction (recall phase) were each carried out either on a computer screen or on the floor of a room, involving actual walking in the recall phase. Combinations of the two different encoding and recall procedures result in the modality conditions Screen-Screen, Screen-Floor, Floor-Screen, and Floor-Floor. Results show the expected decrease in performance with increasing sequence length, which is likely due to processing limitations of working memory. We also found differences in performance between the modality conditions indicating different involvements of spatial working memory processes. Participants performed best in the Screen-Screen modality condition. Floor-Screen and Floor Floor modality conditions require additional working memory resources for reference frame transformation and spatial updating, respectively; the resulting impairment of the performance was about the same in these two conditions. Finally, the Screen-Floor modality condition requires both types of additional spatial demands and led to the poorest performance. Therefore, we suggest that besides the well-known spatial requirements of CSST, additional working memory resources are demanded in walking CSST supporting processes such as spatial updating, mental rotation, reference frame transformation, and the control of walking itself. PMID- 26892884 TI - Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson's disease act under speed pressure. AB - The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed-accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson's disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination 'moving-dots' task to assess speed-accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed-accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD. PMID- 26892886 TI - Gender difference in handgrip strength of Italian children aged 9 to 10 years. AB - BACKGROUND: Handgrip strength is an index of nutritional status which correlates to morbidity and mortality in young. It differs in adults and adolescents between gender. However, it is no clear whether a difference exists also in children aged 9 to 10 years, and which are the factors influencing it. Furthermore, data of Handgrip strength of Italian schoolchildren are lacking. Aim of this study was to provide Handgrip strength value from a sample of healthy Italian schoolchildren aged 9 to 10 years and to determine which factors affect grip strength at this age. METHODS: We enrolled 137 children (boys n =66; girls n = 71) who underwent a body mass index and Handgrip strength measurement. Handgrip strength was assessed by an hydraulic hand dynamometer. RESULTS: The mean handgrip strength value was 13.8 +/- 4.0 for girls and 15.2 +/- 3.0 kg for boys (p = 0.04) thus, we found a significant difference between gender. We have not found a significant differences in anthropometric parameters between gender. In the univariate analysis Handgrip strength was associated with age, BMI, height, weight and gender (p < 0.001 for age, p < 0.001 for BMI, p < 0.001 for height, p < 0.001 for weight and p < 0.04 for gender). The Multivariate linear regression analysis showed that age, BMI and gender were all correlated to grip force. CONCLUSION: We found a significant difference in grip strength between healthy Italian schoolchildren aged 9 to 10 years. This parameter seems to be primarily influenced by gender. Our investigation is important since currently data regarding the reference values of HGS for Italian children are lacking. PMID- 26892887 TI - Overexpression of microRNA-5100 decreases the aggressive phenotype of pancreatic cancer cells by targeting PODXL. AB - Metastasis is the main cause of cancer-associated death, and metastasis of pancreatic cancer remains difficult to treat because of its aggressiveness. MicroRNAs (miRNAs) play crucial roles in the regulation of various human transcripts, and many miRNAs have been reported to correlate with cancer metastasis. We identified an anti-metastatic miRNA, miR-5100, by investigating differences in miRNA profiling between highly metastatic pancreatic cancer cells and their parental cells. Overexpression of miR-5100 inhibited colony formation (P<0.05), cell migration (P<0.0001) and invasion (P<0.0001) of pancreatic cancer cells. In addition, we identified a possible target of miR-5100, podocalyxin-like 1 (PODXL), and demonstrated miR-5100 directly binds to the 3' untranslated region of PODXL and post-transcriptionally regulates its expression in pancreatic cancer cells. Silencing PODXL resulted in diminished cell migration (P<0.0001) and invasion (P<0.05). We also clarified the close relationship between expression of PODXL in human pancreatic cancer specimens and liver metastasis (P=0.0003), and determined that post-operative survival was longer in the low-PODXL expression group than in the high-PODXL expression group (P<0.05). These results indicate that miR-5100 and PODXL have considerable therapeutic potential for anti metastatic therapy and could be potential indicators for cancer metastases in patients with pancreatic cancer. PMID- 26892889 TI - Combined Anterior and Dual Posterolateral Approaches for Ankle Arthroscopy for Posterior and Anterior Ankle Impingement Syndrome. AB - BACKGROUND: We introduce a novel method of combining the standard anteromedial and anterolateral approaches and dual posterolateral approaches in the arthroscopic treatment of posterior and anterior ankle impingement syndrome and compare the postoperative outcomes with conventional anteromedial/anterolateral and posteromedial/posterolateral approaches. METHODS: From January 2013 to January 2015, we treated 28 patients with posterior and anterior ankle impingement syndrome by arthroscopy. The patients were divided into the conventional group (n = 13) and the modified group (n = 15) according to the surgical approaches used in the operation. Preoperative and postoperative American Orthopaedic Foot & Ankle Society (AOFAS) score, visual analog scale (VAS) score, range of ankle motion, and operation time were recorded. The average follow-up was 16 months (range 6-24 months). RESULTS: Posterior and anterior ankle impingement syndrome was confirmed arthroscopically in all patients. After the operation, the range of ankle motion in all patients was restored. There was no significant difference in postoperative AOFAS score, VAS score, dorsiflexion, and plantarflexion between the conventional group and the modified group. Moreover, the operation time was significantly reduced in the modified group compared with the conventional group. There was no recurrence of osteophyte and no complications such as infection, neurovascular injury, or delayed healing of surgical incision in the modified group. CONCLUSIONS: Dual posterolateral approaches combined with standard anteromedial and anterolateral approaches was a novel method for arthroscopic treatment of posterior and anterior ankle impingement syndrome. It proved to be safe and effective, and significantly reduced the operation time. Reposition, repeated prep and drape, and limb distraction were avoided. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26892888 TI - Antimicrobial resistance of Staphylococcus aureus isolated from skin infections and its implications in various clinical conditions in Korea. AB - BACKGROUND: Periodic investigations into patterns of antimicrobial resistance can help to optimize the efficacy of treatment and limit the development of resistance. OBJECTIVES: The aim of this study was to update information on patterns of antimicrobial resistance in Staphylococcus aureus isolated from skin infections in South Korea. METHODS: We retrospectively analyzed clinical information and in vitro antimicrobial resistance data for 965 clinical S. aureus isolates obtained from skin infections during 2010-2013 in a university hospital in South Korea. RESULTS: The rate of resistance to oxacillin (methicillin resistant S. aureus [MRSA]) was 47.4%. Similar rates of resistance to erythromycin (45.6%), fusidic acid (44.0%), and clindamycin (42.3%) were noted. The rate of resistance to mupirocin was 8.4%. Overall, 4.9% of isolates were resistant to both fusidic acid and mupirocin. None of the isolates showed resistance to habekacin, synercid, teicoplanin, or vancomycin. Generally, antimicrobial resistance rates did not increase from 2010 to 2013 except with reference to a few agents such as mupirocin and rifampin. Isolates from surgical patients, inpatients, non-dermatology outpatients, and adult patients showed relatively high rates of resistance to multiple antimicrobials. Resistance to mupirocin was not only lower than that to fusidic acid but was consistent across clinical contexts. CONCLUSIONS: The prevalence of MRSA in skin infections in South Korea did not increase during 2010-2013. Isolates from dermatology outpatients showed relatively lower rates of resistance to multiple antimicrobials than isolates from non-dermatology outpatients. Among topical antimicrobials, resistance to mupirocin was relatively low regardless of clinical condition. PMID- 26892890 TI - Ischemic proctosigmoiditis due to retroperitoneal hematoma. AB - Gastrointestinal ischemia is caused by ischemic colitis in 50-60% of cases and is associated with high morbidity and mortality among patients. Ischemic proctosigmoiditis is a very rare disorder with only few cases reported. Due to collateral blood supply the rectum is only affected in 2-5% of all cases of ischemic colitis. We report a rare case of ischemic proctosigmoiditis caused by a retroperitoneal hematoma due to a pelvic fracture. PMID- 26892891 TI - Systolic Blood Pressure Variability is Associated with Severe Hemorrhagic Transformation in the Early Stage After Thrombolysis. AB - The present study investigates the association between hour-to-hour blood pressure (BP) variability and severe hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) during hyperacute stage. We analyzed hour-to-hour BP measurement within 24 h after IVT in patients with acute ischemic stroke. We calculated the maximum, minimum, and average (mean) of 24-h BP values, and BP variability profiles including standard deviation (SD), average squared difference between successive measurements (SV), average squared difference between rise and drop successive measurements (SV rise and SV drop), and maximum of SV rise and SV drop (SVrisemax and SVdropmax) after quartering 0-to-24 h BP course. HT was classified as hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracerebral hemorrhage (sICH) was defined as HT with worsening of the National Institute of Health Stroke Scale score by >=4 points or leading to death. Severe HT was defined as either PH or sICH. Totally, 461 patients were included. We observed HT in 142 (30.8 %), PH in 43 (9.3 %), and sICH in 12 (2.6 %) patients. Binary logistic regression indicated that SBPSD and SBPSV within the first 24 h were associated with sICH (OR, 4.538; 95 % CI, 1.834 11.230; p = 0.001 and OR, 6.117; 95 % CI, 2.000-18.711; p = 0.002) and PH (OR, 2.146; 95 % CI, 1.106-4.165; p = 0.024 and OR, 2.202; 95 % CI, 1.046-4.633; p = 0.038). For the SBP SV parameters among four periods of the initial 24 h, only SV, SVrise, and SVrisemax during the first 6 h were significantly associated with sICH (OR, 2.785; 95 % CI, 1.294-5.994; p = 0.009; OR, 1.825; 95 % CI, 1.110 3.002; p = 0.018 and OR, 1.495; 95 % CI, 1.039-2.149; p = 0.030) and PH (OR, 2.088; 95 % CI, 1.287-3.387; p = 0.003; OR, 1.501; 95 % CI, 1.044-2.156; p = 0.028 and OR, 1.334; 95 % CI, 1.023-1.739; p = 0.033). High systolic BP variability during the first 6 h after IVT was related with severe HTs, which highlights the potential predictability to severe HTs. PMID- 26892893 TI - Patterns of return to oral intake and decannulation post-tracheostomy across clinical populations in an acute inpatient setting. AB - BACKGROUND: Dysphagia is often a comorbidity in patients who require a tracheostomy, yet little is known about patterns of oral intake commencement in tracheostomized patients, or how patterns may vary depending on the clinical population and/or reason for tracheostomy insertion. AIMS: To document patterns of clinical management around the commencement of oral intake throughout hospital admission and along the decannulation pathway in patients with a new tracheostomy, and to examine the nature of variability across multiple clinical populations. METHODS & PROCEDURES: A 12-month retrospective review of 126 patients who had undergone an acute tracheostomy was conducted. Within the cohort, patients were further classified into eight clinical populations representing specialty areas within the tertiary referral centre. Data were collected on timing of milestones and patterns of clinical management related to oral and enteral feeding and decannulation. Relationships between temporal variables were calculated, in addition to descriptive analysis of the overall cohort and by clinical population. OUTCOMES & RESULTS: Median temporal markers of patient progression post-tracheostomy insertion for the cohort were: continuous cuff deflation after 7.5 days, commencement of oral intake after 10.5 days, decannulation after 15 days and cessation of enteral nutrition (EN) after 17 days. However, considerable individual variation and differences between clinical populations was observed. Overall, 86% of the cohort returned to oral intake, although 25% were discharged with EN via a gastrostomy. A total of 86% of the group were decannulated by hospital discharge. Oral intake was introduced at every stage of the decannulation pathway, including prior to cuff deflation, but the majority of patients commenced diet/fluids following cuff deflation or with an uncuffed tube in situ, and most patients who ceased EN did so following decannulation. Commencement of oral intake was evenly split between the intensive care unit (ICU) and the wards. Increased time to commencement of oral intake correlated with increased time to decannulation (r = .805, p = .001), and increased time to decannulation correlated with increased hospital length of stay (r = .687, p = .006). Whilst cohort patterns were observed within the heterogeneous group, sub-analysis revealed distinct patterns of oral intake management across the different clinical populations. CONCLUSIONS & IMPLICATIONS: The data provide benchmarks enabling comparison by overall cohort as well as by specialist clinical populations, each with differing reasons for tracheostomy insertion. The data would suggest that tracheostomy patients should not be looked upon as a singular cohort; rather, evaluation of factors with specific attention made to underlying aetiology and individual clinical presentation is essential. PMID- 26892892 TI - Administration of Antithymocyte Globulin (Rabbit) to Treat a Severe, Mixed Rejection Episode in a Pregnant Renal Transplant Recipient. AB - Pregnancy in solid organ transplant recipients carries numerous risks to the mother such as increased risk of rejection, gestational diabetes mellitus, and preeclampsia. The developing fetus is subjected to risks such as birth defects, preterm delivery, and low birth weight. Typically, these risks can be managed through intensive, multidisciplinary prenatal care and a proper immunosuppressive regimen. In the setting of rejection, however, little data are available to suggest safe and effective treatment of acute cellular rejection, antibody mediated rejection, or mixed rejection episodes in the pregnant solid organ transplant recipient. We describe the first case, to our knowledge, in which antithymocyte globulin (rabbit) was used to successfully treat a pregnant renal transplant recipient who experienced a mixed rejection episode. A 22-year-old, African American woman with stage 6 chronic kidney disease received a deceased donor renal transplant after undergoing hemodialysis for 3 years. Her maintenance immunosuppressive regimen at the time of transplantation consisted of tacrolimus, prednisone, and mycophenolate mofetil. Despite counseling efforts on the importance of having a planned pregnancy after kidney transplantation so that her immunosuppressive medications could be optimized, the patient became pregnant 12 months later; her mycophenolate mofetil was changed to azathioprine to reduce the risk of fetal deformities or death. Three months later, the patient was admitted for biopsy of her transplanted kidney and was evaluated for possible kidney rejection. After confirmation of a mixed 1B acute cellular rejection and antibody mediated rejection episode, the patient decided to pursue resolution of her rejection episode and continue the pregnancy despite the potential risks to the fetus. She was treated with high-dose corticosteroids, intravenous immunoglobulin, plasmapheresis, and antithymocyte globulin (rabbit). Twenty-nine months after transplantation, the patient was induced and gave birth to a healthy baby boy. Our patient's case offers unique insight into the potential management of a rejection episode requiring aggressive immunosuppressive therapy. Although potent immunosuppressive therapies were successfully used in our patient, further studies are needed to make definitive recommendations regarding the use of such therapies for treatment of rejection episodes in pregnant solid organ transplant recipients. The risks and uncertainties of treating rejection episodes should always be discussed with and understood by the patient before an informed decision is made. PMID- 26892895 TI - The effects of fluid shear stress on proliferation and osteogenesis of human periodontal ligament cells. AB - Shear stress is one of the main stress type produced by speech, mastication or tooth movement. The mechano-response of human periodontal ligament (PDL) cells by shear stress and the mechanism are largely unknown. In our study, we investigated the effects of fluid shear stress on proliferation, migration and osteogenic potential of human PDL cells. 6dyn/cm(2) of fluid shear stress was produced in a parallel plate flow chamber. Our results demonstrated that fluid shear stress rearranged the orientation of human PDL cells. In addition, fluid shear stress inhibited human PDL cell proliferation and migration, but increased the osteogenic potential and expression of several growth factors and cytokines. Our study suggested that shear stress is involved in homeostasis regulation in human PDL cells. Inhibiting proliferation and migration potentially induce PDL cells to respond to mechanical stimuli in order to undergo osteogenic differentiation. PMID- 26892896 TI - Biomechanical properties of lumbar endplates and their correlation with MRI findings of lumbar degeneration. AB - How stiffness and strength of the human lumbar endplate vary with location, spinal level, and its correlation with MRI findings of lumbar degeneration, has not been reported in detail. 27 lumbar spines (16 male, 11 female, 31-49yrs) were harvested from cadavers without history of lumbar lesion or trauma. Disc and endplate degeneration was evaluated from MRI. Micro-CT was used to evaluate endplate microstructure. Indentation tests were performed to quantify stiffness and strength at 23 sites on each endplate from load-displacement graphs. Results showed that stiffness and strength increased from the centre of the endplate towards its periphery. There was no general age-related reduction in endplate stiffness or strength, although strength decreased slightly with age opposite the inner annulus. Disc degeneration was associated with a 39-46% decrease in stiffness, and a 21-30% decrease in strength, with effects being greatest near the endplate periphery. The presence of Modic changes had a similar effect. Strength and stiffness consistently increased at lower spinal levels, and were consistently greater in the inferior endplate (relative to the vertebra). Gender had little influence, although stiffness in the peripheral endplate was greater in males. BV/TV, SMI, Tb.Th and BMD were positively correlated with strength. We conclude that endplate properties reflect compressive stresses within adjacent intervertebral discs. Weaker and softer endplates may indicate reduced mechanical loading in decompressed discs that are stress-shielded by the neural arch. Preoperative MRI evaluation of endplate integrity could reduce the risk of implant subsidence following inter-body fusion. PMID- 26892894 TI - Long-term High Fat Ketogenic Diet Promotes Renal Tumor Growth in a Rat Model of Tuberous Sclerosis. AB - Nutritional imbalance underlies many disease processes but can be very beneficial in certain cases; for instance, the antiepileptic action of a high fat and low carbohydrate ketogenic diet. Besides this therapeutic feature it is not clear how this abundant fat supply may affect homeostasis, leading to side effects. A ketogenic diet is used as anti-seizure therapy i.a. in tuberous sclerosis patients, but its impact on concomitant tumor growth is not known. To examine this we have evaluated the growth of renal lesions in Eker rats (Tsc2+/-) subjected to a ketogenic diet for 4, 6 and 8 months. In spite of existing opinions about the anticancer actions of a ketogenic diet, we have shown that this anti-seizure therapy, especially in its long term usage, leads to excessive tumor growth. Prolonged feeding of a ketogenic diet promotes the growth of renal tumors by recruiting ERK1/2 and mTOR which are associated with the accumulation of oleic acid and the overproduction of growth hormone. Simultaneously, we observed that Nrf2, p53 and 8-oxoguanine glycosylase alpha dependent antitumor mechanisms were launched by the ketogenic diet. However, the pro-cancerous mechanisms finally took the ascendency by boosting tumor growth. PMID- 26892897 TI - Sticky fingers: Adhesive properties of human fingertips. AB - Fingertip friction is a rather well studied subject. Although the phenomenon of finger stickiness is known as well, the pull-off force and the adhesive strength of human finger tips have never been previously quantified. For the first time, we provided here characterization of adhesive properties of human fingers under natural conditions. Human fingers can generate a maximum adhesive force of 15mN on a smooth surface of epoxy resin. A weak correlation of the adhesive force and the normal force was found on all test surfaces. Up to 300mN load, an increase of the normal force leads to an increase of the adhesive force. On rough surfaces, the adhesive strength is significantly reduced. Our data collected from untreated hands give also an impression of an enormous scattering of digital adhesion depending on a large set of inter-subject variability and time-dependent individual factors (skin texture, moisture level, perspiration). The wide inter- and intra-individual range of digital adhesion should be considered in developing of technical and medical products. PMID- 26892898 TI - A stricter condition for standing balance after unexpected perturbations. AB - In order to account for the dynamic nature of balance, the concept of the 'extrapolated centre of mass' XcoM has been introduced (Hof et al., 2005). The law for standing balance was then formulated as: the XcoM should remain within the Base of Support (BoS). This law, however, does not take into account that the centre of pressure (CoP) needs time to displace due to various neural and mechanical delays. The theory is extended to include the finite reaction- and displacement time of the CoP. Experimental results on humans standing on two feet undergoing sudden postural perturbations are presented. In this case it turns out that the area of the effective BoS is only a fraction, some 30%, of the area of the static BoS. PMID- 26892899 TI - Sagittal rotational stiffness and damping increase in a porcine lumbar spine with increased or prolonged loading. AB - While the impact of load magnitude on spine dynamic parameters (stiffness and damping) has been reported, it is unclear how load history (exposure to prolonged loading) affects spine dynamic parameters in sagittal rotation. Furthermore, it is unknown if both spine stiffness and damping are equally affected to prolonged loading. Using a pendulum testing apparatus, the effect of load magnitude and load history on spine sagittal rotational stiffness and damping was assessed. Nine porcine lumbar functional spine units (FSUs) were tested in an increasing compressive load phase (ICP: 44.85, 68.55, 91.75, 114.6kg) and then a decreasing compressive load phase (DCP: 91.75, 68.55, and 44.85kg). Each trial consisted of flexing the FSU 5 degrees and allowing it to oscillate unconstrained. During the ICP, both stiffness and damping linearly increased with load. However, in the DCP, stiffness and damping values were significantly higher than the identical load collected during the ICP, suggesting load history affects sagittal rotational dynamic parameters. In addition, spine damping was more affected by load history than spine stiffness. These results highlight the importance of controlling load magnitude and history when assessing spine dynamic parameters. PMID- 26892900 TI - Chemical Partition of the Radiative Decay Rate of Luminescence of Europium Complexes. AB - The spontaneous emission coefficient, Arad, a global molecular property, is one of the most important quantities related to the luminescence of complexes of lanthanide ions. In this work, by suitable algebraic transformations of the matrices involved, we introduce a partition that allows us to compute, for the first time, the individual effects of each ligand on Arad, a property of the molecule as a whole. Such a chemical partition thus opens possibilities for the comprehension of the role of each of the ligands and their interactions on the luminescence of europium coordination compounds. As an example, we applied the chemical partition to the case of repeating non-ionic ligand ternary complexes of europium(III) with DBM, TTA, and BTFA, showing that it allowed us to correctly order, in an a priori manner, the non-obvious pair combinations of non-ionic ligands that led to mixed-ligand compounds with larger values of Arad. PMID- 26892901 TI - Bipolar versus monopolar transurethral resection of the prostate for benign prostatic hyperplasia: safe in patients with high surgical risk. AB - Here, we compared the effects of bipolar and monopolar transurethral resection of the prostate (B-TURP, M-TURP) for treating elderly patients (>=75 years) with benign prostatic hyperplasia(BPH) who had internal comorbidities. Eligible BPH patients were aged >=75 years and had at least one internal comorbidity. In this open-label, prospective trial, patients were assigned to B-TURP (n = 75) and M TURP (n = 88) groups. Data on prostate volume (PV), urination, and time during perioperative period were compared; data associated with urination and complications at one year postoperatively were also compared. Finally, follow-up data were available for 68 and 81 patients in the B-TURP and M-TURP group, respectively. No deaths were recorded. Intraoperative bleeding was lower and irrigation time, indwelling catheter time, and hospital stay were shorter in the B-TURP group than in the M-TURP group (p < 0.001). No difference was observed with respect to operation time (p = 0.058). At one year after the operation, differences with respect to urination and complications were not significant. In conclusion, Short-term efficacy of B-TURP or M-TURP was satisfactory for elderly patients with BPH who had internal comorbidities. Besides, B-TURP is a more sensible choice because it has a lower prevalence of adverse effects. PMID- 26892903 TI - Corrigendum. PMID- 26892904 TI - Corrigendum. PMID- 26892905 TI - Phase-driven magneto-electrical characteristics of single-layer MoS2. AB - Magnetism of the MoS2 semiconducting atomic layer was highlighted for its great potential in the applications of spintronics and valleytronics. In this study, we demonstrate an evolution of magneto-electrical properties of single layer MoS2 with the modulation of defect configurations and formation of a partial 1T phase. With Ar treatment, sulfur was depleted within the MoS2 flake leading to a 2H (low spin) -> partial 1T (high-spin) phase transition. The phase transition was accompanied by the development of a ferromagnetic phase. Alternatively, the phase transition could be driven by the desorption of S atoms at the edge of MoS2via O2 treatment while with a different ordering magnitude in magnetism. The edge sensitive magnetism of the single-layer MoS2 was monitored by magnetic force microscopy and validated by a first-principle calculation with graded-Vs (sulfur vacancy) terminals set at the edge, where band-splitting appeared more prominent with increasing Vs. Treatment with Ar and O2 enabled a dual electrical characteristic of the field effect transistor (FET) that featured linear and saturated responses of different magnitudes in the Ids-Vds curves, whereas the pristine MoS2 FET displayed only a linear electrical dependency. The correlation and tuning of the Vs-1T phase transition would provide a playground for tailoring the phase-driven properties of MoS2 semiconducting atomic layers in spintronic applications. PMID- 26892902 TI - Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate. AB - IMPORTANCE: Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is a chlorotoxin-based, tumor-targeting agent that has not yet been studied in HNSCC. OBJECTIVE: To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. DESIGN, SETTING, AND PARTICIPANTS: This was an observational study (including sensitivity and specificity analysis) of BLZ 100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen induced dysplasia model of hamster cheek pouches. INTERVENTIONS: Various HNSCC xenografts were established in the tongues of NOD-scid IL2Rgammanull (NSG) mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) was applied to the cheek pouch of Golden Syrian hamsters for 9 to16 weeks. BLZ-100 was subcutaneously injected, and fluorescence uptake was measured. MAIN OUTCOMES AND MEASURES: The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades. RESULTS: In HNSCC xenografts, BLZ 100 demonstrated a mean (SD) SBR of 2.51 (0.47). The ROC curve demonstrated an area under the curve (AUC) of 0.89; an SBR of 2.50 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and nontumor interface, the AUC increased to 0.97; an SBR of 2.50 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 [0.71] vs 1.51 [0.34], P = .006). CONCLUSIONS AND RELEVANCE: BLZ-100 is a sensitive and specific marker of HNSCC and can distinguish high-risk from low risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of premalignant lesions. PMID- 26892907 TI - NaKV4O9.2H2O: a new 2D magnetic compound with a 1/5-depleted square lattice. AB - A new vanadate compound NaKV4O9.2H2O is successfully synthesized by a conventional hydrothermal method. This compound crystallizes in the monoclinic system with the space group C2/c, showing a typical 2D layered structure built from VO5 pyramids, in which the layers are separated by Na(+), K(+), and H2O. The topology structure of magnetic V(4+) ions shows a quite interesting 1/5-depleted square lattice, which is quite similar to that of a famous low-dimensional quantum spin system CaV4O9. A structural and magnetic comparison confirmed that the title compound may exhibit a more pronounced 2D character with a large spin gap. PMID- 26892906 TI - Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study. AB - We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb. PMID- 26892908 TI - The Affordable Care Act and Diabetes Diagnosis and Care: Exploring the Potential Impacts. AB - This article reviews available data on the implications of the Affordable Care Act (ACA) for the diagnosis and care of type 2 diabetes. We provide a general overview of the major issues for diabetes diagnosis and care, and describe the policies in the ACA that affect diabetes diagnosis and care. We also estimate that approximately 2.3 million of the 4.6 million people in the USA with undiagnosed diabetes aged 18-64 in 2009-2010 may have gained access to free preventive care under the ACA, which could increase diabetes detection. In addition, we note two factors that may limit the success of the ACA for improving access to diabetes care. First, many states with the highest diabetes prevalence have not expanded Medicaid eligibility, and second, primary care providers may not adequately meet the increase in Medicaid patients because federal funding to increase provider reimbursement for Medicaid visits recently expired. We close by discussing current gaps in the literature and future directions for research on the ACA's impact on diabetes diagnosis, care, and health outcomes. PMID- 26892909 TI - Family-Based Interventions in Preventing Children and Adolescents from Using Tobacco: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Tobacco is the main preventable cause of death and disease worldwide. Adolescent smoking is increasing in many countries with poorer countries following the earlier experiences of affluent countries. Preventing adolescents from starting smoking is crucial to decreasing tobacco-related illness. OBJECTIVE: To assess effectiveness of family-based interventions alone and combined with school-based interventions to prevent children and adolescents from initiating tobacco use. DATA SOURCES: Fourteen bibliographic databases and the Internet, journals hand-searched, and experts consulted. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Randomized controlled trials (RCTs) with children or adolescents and families, interventions to prevent starting tobacco use, and follow-up >=6 months. STUDY APPRAISAL/SYNTHESIS METHODS: Abstracts/titles independently assessed and data independently entered by 2 authors. Risk of bias was assessed with the Cochrane Risk-of-Bias tool. RESULTS: Twenty-seven RCTs were included. Nine trials of never-smokers compared with a control provided data for meta-analysis. Family intervention trials had significantly fewer students who started smoking. Meta-analysis of 2 RCTs of combined family and school interventions compared with school only, showed additional significant benefit. The common feature of effective high-intensity interventions was encouraging authoritative parenting. LIMITATIONS: Only 14 RCTs provided data for meta-analysis (approximately a third of participants). Of the 13 RCTs that did not provide data for meta-analysis 8 compared a family intervention with no intervention and 1 reported significant effects, and 5 compared a family combined with school intervention with a school intervention only and none reported additional significant effects. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: There is moderate-quality evidence that family based interventions prevent children and adolescents from starting to smoke. PMID- 26892910 TI - Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization. AB - Psychiatric hospitals are increasingly adopting smoke-free policies. Tobacco use is common among persons with mental illness, and nicotine withdrawal (NW), which includes symptoms of depression, anxiety, anger/irritability, and sleep disturbance, may confound psychiatric assessment and treatment in the inpatient setting. This study aimed to characterize NW and correlates of NW severity in a sample of smokers hospitalized for treatment of mental illness in California. Participants (N=754) were enrolled between 2009 and 2013, and averaged 17 (SD=10) cigarettes/day prior to hospitalization. Though most (70%) received nicotine replacement therapy (NRT) during hospitalization, a majority (65%) reported experiencing moderate to severe NW. In a general linear regression model, NW symptoms were more severe for women, African American patients, and polysubstance abusers. Though invariant by psychiatric diagnostic category, greater NW was associated with more severe overall psychopathology and greater cigarette dependence. The full model explained 46% of the total variation in NW symptom severity (F [19, 470]=23.03 p<0.001). A minority of participants (13%) refused NRT during hospitalization. Those who refused NRT reported milder cigarette dependence and stated no prior use of NRT. Among smokers hospitalized for mental illness, NW severity appears multidetermined, related to cigarette dependence, demographic variables, psychiatric symptom severity, and other substance use. Assessment and treatment of NW in the psychiatric hospital is clinically warranted and with extra attention to groups that may be more vulnerable or naive to cessation pharmacotherapy. PMID- 26892912 TI - Reading the conflict of interest statement is as important as reading the result section: Response to the letter by Dr. Kosmider: ideology versus evidence: investigating the claim that the literature on e-cigarettes is undermined by material conflict of interest. PMID- 26892911 TI - Financial incentives to promote cardiac rehabilitation participation and adherence among Medicaid patients. AB - PURPOSE: Cardiac rehabilitation (CR) improves medical outcomes after myocardial infarction or coronary revascularization. Lower socioeconomic status (SES) patients are less likely to participate in and complete CR. The aim of this study was to test whether financial incentives may increase participation and adherence to CR among lower-SES patients. METHODS: Patients eligible to participate in CR with Medicaid insurance coverage were approached for inclusion. Patients were placed on an escalating incentive schedule of financial incentives contingent upon CR attendance. CR participation was compared to a usual care group of 101 Medicaid patients eligible for CR in the 18months prior to the study. Attendance (participating in >=one CR sessions) and adherence (sessions completed out of 36) were compared between groups. The study was conducted in Vermont, USA, 2013-2015. RESULTS: Of 13 patients approached to be in the study and receive incentives, 10 (77%) agreed to participate. All 10 patients completed at least one session of CR, significantly greater than the 25/101 (25%) in the control condition (p<0.001). Of patients in both groups who attended at least one session of CR, adherence was higher in the intervention group (average of 31.1 sessions completed vs. 13.6 in the control group, p<0.001). CR completion rates were also higher during the intervention with 8 of 10 (80%) intervention patients completing all 36 sessions compared to only 2 of 25 (8%) control patients (p<0.001). CONCLUSIONS: Financial incentives may be an efficacious strategy for increasing CR participation and adherence among Medicaid patients. PMID- 26892914 TI - Allosteric Mechanisms of Molecular Machines at the Membrane: Transport by Sodium Coupled Symporters. AB - Solute transport across cell membranes is ubiquitous in biology as an essential physiological process. Secondary active transporters couple the unfavorable process of solute transport against its concentration gradient to the energetically favorable transport of one or several ions. The study of such transporters over several decades indicates that their function involves complex allosteric mechanisms that are progressively being revealed in atomistic detail. We focus on two well-characterized sodium-coupled symporters: the bacterial amino acid transporter LeuT, which is the prototype for the "gated pore" mechanism in the mammalian synaptic monoamine transporters, and the archaeal GltPh, which is the prototype for the "elevator" mechanism in the mammalian excitatory amino acid transporters. We present the evidence for the role of allostery in the context of a quantitative formalism that can reconcile biochemical and biophysical data and thereby connects directly to recent insights into the molecular structure and dynamics of these proteins. We demonstrate that, while the structures and mechanisms of these transporters are very different, the available data suggest a common role of specific models of allostery in their functions. We argue that such allosteric mechanisms appear essential not only for sodium-coupled symport in general but also for the function of other types of molecular machines in the membrane. PMID- 26892913 TI - Exposure and response to current text-only smokeless tobacco health warnings among smokeless tobacco users aged >=18years, United States, 2012-2013. AB - INTRODUCTION: We assessed US adult smokeless tobacco (SLT) users' exposure and response to SLT health warnings, which are currently in text-only format, covering 30% of the two primary surfaces of SLT containers and 20% of advertisements. METHODS: Data were from the 2012-2013 National Adult Tobacco Survey. Past 30-day exposure to SLT health warnings among past 30-day SLT users (n=1626) was a self-report of seeing warnings on SLT packages: "Very often," "Often," or "Sometimes" (versus "Rarely" or "Never"). We measured the association between SLT health warning exposure and perceptions of SLT harmfulness and addictiveness using logistic regression. RESULTS: Of past 30-day SLT users, 77.5% reported exposure to SLT health warnings, with lower prevalence reported among females and users of novel SLT products (snus/dissolvable tobacco). Furthermore, exposure reduced linearly with reducing education and annual household income (p<0.01). Among exposed past 30-day SLT users, 73.9% reported thinking about the health risks of SLT, while 17.1% reported stopping SLT use on >=1 occasion within the past 30days. Exposure to SLT warnings was associated with perceived SLT harmfulness (AOR=2.16; 95% CI=1.15-4.04), but not with perceived SLT addictiveness. CONCLUSION: Socioeconomic disparities found in exposure and response to SLT health warnings can be addressed through implementation of large pictorial warnings. PMID- 26892916 TI - Image contrast reduction mechanism in full-field optical coherence tomography. AB - Correct interpretation of image contrast obtained with full-field optical coherence tomography (FFOCT) technique is required for accurate medical diagnosis applications. In this work, first, the characteristics of microscopic structures of tissue that generate the contrast in en-face tomographic image obtained with FFOCT are discussed. Then an overview is given of the parameters that affect image contrast. Finally, the contrast correction factor for correct image interpretation and the contrast limits to practical FFOCT systems are outlined. PMID- 26892915 TI - Solvent-Driven Gate Opening in MOF-76-Ce: Effect on CO2 Adsorption. AB - A cerium-based metal-organic framework with MOF-76 topology has been synthesized by a very simple and fast solvothermal method that has been tested for a one gram yield. Variable-temperature powder XRD and X-ray absorption data, analyzed by Rietveld and multiple-scattering extended X-ray absorption fine-structure methods, revealed high thermal stability and the presence of three different stable structures. X-ray absorption near-edge structure and FTIR spectroscopy probed the presence of cerium(III), which was characterized by coordinatively unsaturated sites that, however, played no major role in carbon dioxide adsorption. The material revealed excellent carbon dioxide adsorption properties: the highest gravimetric capacity of 15 wt% was observed at 1.1 bar in the case of the sample activated at 250 degrees C in vacuum, whereas the strongest interaction energy of 35 kJ mol(-1) was observed for the sample activated at 150 degrees C. Negligible nitrogen uptake of the sample activated at 150 degrees C indicates that this material is a promising candidate for nitrogen/carbon dioxide separation purposes. PMID- 26892917 TI - Microstructure and oxidation behaviour investigation of rhodium modified aluminide coating deposited on CMSX 4 superalloy. AB - The CMSX 4 superalloy was coated with rhodium 0.5-MUm thick layer and next aluminized by the CVD method. The coating consisted of two layers: the additive and the interdiffusion one. The outward diffusion of nickel from the substrate turned out to be a coating growth dominating factor. The additive layer consists of the beta-NiAl phase, whereas the interdiffusion layer consists of the beta NiAl phase with precipitates of sigma and MU phases. Rhodium has dissolved in the coating up to the same level in the matrix and in the precipitates. The oxidation test proved that the rhodium modified aluminide coating showed about twice better oxidation resistance than the nonmodified one. PMID- 26892918 TI - Reply to: Paul SP, et al. (2016) the debate continues: is urine culture indicated in neonates with prolonged jaundice? PMID- 26892919 TI - Diffusion-weighted quantitative MRI to diagnose benign conditions from malignancies of the anterior mediastinum: Improvement of diagnostic accuracy by comparing perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient. AB - PURPOSE: To compare perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient (ADC) to diagnose benign conditions from malignancies of the anterior mediastinum. MATERIALS AND METHODS: Seventy-six subjects were divided into a "benign conditions" group (A, n = 44) and a "malignancies" group (B, n = 32), based on histological findings. diffusion weighted magnetic resonance imaging (DW-MRI) was performed at b of 0/150/800 sec/mm(2) . The ADCs were obtained on an ADC map by including (perfusion sensitive = ADCb0-800 ) and excluding (perfusion-free = ADCb150-800 ) the b = 0 sec/mm(2) . The Mann-Whitney U-test was used to detect differences in ADCb0-800 compared with ADCb150-800 values between all cases, benign conditions, and malignancies. The same test was used to evaluate differences in ADCs between the two groups for each type of measurement (ADCb0-800 and ADCb150-800 ), and receiver-operating characteristic (ROC) curves were obtained to evaluate discrimination abilities with comparison of areas-under-ROC-curves (AUROC). Optimal cutpoints for discrimination between groups were determined by the Youden Index with computation of accuracy. RESULTS: The median ADCb0-800 was significantly greater compared with ADCb150-800 for all cases (P = 0.0014), benign conditions (P = 0.0412), and malignancies (P = 0.0001). The median percentage of increase was 5.30% for group-A and 22.39% for group-B (P < 0.0001). AUROC of ADC in discriminating between groups was significantly greater for ADCb150-800 (0.932) compared with ADCb0-800 (0.831) (P = 0.001). The optimal cutpoint for distinction between groups was 1.52 * 10(-3) mm(2) /sec (sensitivity = 93.7%, specificity = 88.6%, accuracy = 90.8%) for ADCb150-800 and 1.75 * 10(-3) mm(2) /sec (sensitivity = 75.0%, specificity = 79.5%, accuracy = 77.6%) for ADCb0 800 . CONCLUSION: The use of perfusion-free ADC measurements significantly improves diagnostic accuracy of DW-MRI in differentiating benign conditions from malignancies of the anterior mediastinum. J. Magn. Reson. Imaging 2016;44:758 769. PMID- 26892920 TI - Reflections on physical activity intervention research in young people - dos, don'ts, and critical thoughts. AB - BACKGROUND: Physical activity has been associated with many benefits throughout the life course. As levels of physical activity appear to be insufficient in large populations, the development of effective interventions to promote or maintain activity levels in young people are therefore of key public health concern. Physical activity intervention research in young people is challenging, but this should not be a reason to continue conducting inferior quality evaluations. This paper highlights some of the key issues that require more careful and consistent consideration to enable future research to achieve meaningful impact. DISCUSSION: This paper critically evaluates, amongst others, current research practice regarding intervention development, targeting, active involvement of the target population, challenge of recruitment and retention, measurement and evaluation protocols, long-term follow-up, economic evaluation, process evaluation, and publication. It argues that funders and researchers should collaborate to ensure high quality long-term evaluations are prioritised and that a trial's success should be defined by its quality, not its achieved effect. The conduct and publication of well-designed evaluations of well-defined interventions is crucial to advance the field of youth physical activity promotion and make us better understand which intervention strategies may or may not work, why, and for whom. PMID- 26892921 TI - Soft Corals Biodiversity in the Egyptian Red Sea: A Comparative MS and NMR Metabolomics Approach of Wild and Aquarium Grown Species. AB - Marine life has developed unique metabolic and physiologic capabilities and advanced symbiotic relationships to survive in the varied and complex marine ecosystems. Herein, metabolite composition of the soft coral genus Sarcophyton was profiled with respect to its species and different habitats along the coastal Egyptian Red Sea via (1)H NMR and ultra performance liquid chromatography-mass spectrometry (UPLC-MS) large-scale metabolomics analyses. The current study extends the application of comparative secondary metabolite profiling from plants to corals revealing for metabolite compositional differences among its species via a comparative MS and NMR approach. This was applied for the first time to investigate the metabolism of 16 Sarcophyton species in the context of their genetic diversity or growth habitat. Under optimized conditions, we were able to simultaneously identify 120 metabolites including 65 diterpenes, 8 sesquiterpenes, 18 sterols, and 15 oxylipids. Principal component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS) were used to define both similarities and differences among samples. For a compound based classification of coral species, UPLC-MS was found to be more effective than NMR. The main differentiations emanate from cembranoids and oxylipids. The specific metabolites that contribute to discrimination between soft corals of S. ehrenbergi from the three different growing habitats also belonged to cembrane type diterpenes, with aquarium S. ehrenbergi corals being less enriched in cembranoids compared to sea corals. PCA using either NMR or UPLC-MS data sets was found equally effective in predicting the species origin of unknown Sarcophyton. Cyclopropane containing sterols observed in abundance in corals may act as cellular membrane protectant against the action of coral toxins, that is, cembranoids. PMID- 26892922 TI - Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [(11)C]-PE2I. AB - Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction. PMID- 26892924 TI - [PCR-based detection of pathogens in clinical rheumatology]. AB - In the differential diagnostics of autoimmune-mediated rheumatic diseases, rheumatologists often have to consider infections (e. g. Lyme arthritis) or reactive diseases (e. g. reactive arthritis after urogenital bacterial infections). Furthermore, infections with an atypical presentation or caused by atypical pathogens (opportunistic infections) can complicate the immunosuppressive therapy of autoimmune diseases. For this purpose not only conventional microbiological culture methods but also PCR-based methods are increasingly being applied for the direct detection of pathogens in clinical specimens. The aim of this overview is to present commonly used PCR methods in the clinical practice of rheumatology and to describe their benefits and limitations compared to culture-based detection methods. PMID- 26892923 TI - Relationship and prognostic importance of thyroid hormone and N-terminal pro-B Type natriuretic peptide for patients after acute coronary syndromes: a longitudinal observational study. AB - BACKGROUND: Altered thyroid function and increased rates of N-terminal pro-B-Type natriuretic peptide (NT-pro-BNP) are highly prevalent in coronary artery disease (CAD) patients with heart failure, and are associated with unfavorable prognosis. This study was undertaken to examine the relationship and prognostic impact of thyroid hormones, inflammatory biomarkers, and NT-pro-BNP on long-term outcomes in patients after acute coronary syndrome (ACS). METHODS: The study comprised of 642 patients (age 58 +/- 10 years, 77% male) attending an in-patient cardiac rehabilitation program after experiencing ACS. Patients were evaluated for demographic, clinical and CAD risk factors as well as thyroid hormones (e.g., fT3, fT4 level, fT3/fT4 ratio), inflammatory biomarkers (hs-CRP, IL-6) and NT-pro BNP levels. Data on fT3/fT4 ratio and NT-pro-BNP levels were not normally distributed and were natural-log transformed (ln). Both all-cause (cumulative) and cardiac-related mortality were considered the primary outcomes of interest. RESULTS: According to the Cox model, age, NYHA class, (ln)NT-pro-BNP levels (HR 1.53, 95% CI 1.13-2.07), fT4 level (HR 1.15, 95% CI 1.04-1.27), and (ln)fT3/fT4 ratio (HR 0.08, 95% CI 0.02-0.32) were the most important predictors of all-cause mortality among CAD patients after ACS. Similarly, age, NYHA class, (ln)NT-pro BNP levels (HR 1.62, 95% CI 1.11-2.36), fT4 (HR 1.15, 95% CI 1.02-1.29) and (ln)fT3/fT4 ratio (HR 0.10, 95% CI 0.02-0.55) independently predicted cardiac related mortality. Kaplan-Meier analyses provided significant prognostic information with the highest risk for all-cause mortality in the low cut off measures of fT3/fT4 ratio <0.206 and NT-pro-BNP >= 290.4 ng/L (HR 2.03, 95% CI 1.39-2.96) and fT4 level >12.54 pg/ml (HR = 2.34, 95% CI 1.05-5.18). There was no association between hs-CRP, IL-6 and mortality in CAD patients after ACS. CONCLUSIONS: Thyroid hormones (i.e., fT4 level and fT3/fT4 ratio) together with NT-pro-BNP level may be valuable and simple predictors of long-term outcomes of CAD patients after experiencing ACS. PMID- 26892927 TI - Addressing structural challenges for the sexual health and well-being of Indigenous women in Australia. PMID- 26892926 TI - Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity. AB - Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo. PMID- 26892928 TI - What is the future of GUM training? PMID- 26892929 TI - Raltegravir-based HIV postexposure prophylaxis (PEP) in a real-life clinical setting: fewer drug-drug interactions (DDIs) with improved adherence and tolerability. PMID- 26892925 TI - [Pain syndrome of the musculoskeletal system in children and adolescents]. AB - Chronic pain syndromes in children and adolescents are defined as continuous or recurrent pain without an underlying causative diagnosis and lasting for more than 3 months. It is estimated that every fourth child in Germany suffers from chronic pain with every twentieth suffering from extreme recurrent pain. The incidence of chronic pain in children and adolescents is increasing with headache, abdominal pain and musculoskeletal pain being the most frequent. The quality of life declines not only due to the pain but to relieving postural and psychological factors, such as fear and sadness. School attendance, social activities and hobbies are mostly affected. This review summarizes the background of chronic pain syndromes and introduces a multimodal therapeutic approach. PMID- 26892930 TI - What is the most appropriate treatment for rectal Chlamydia trachomatis infection? PMID- 26892931 TI - Dissolution and ionization of sodium superoxide in sodium-oxygen batteries. AB - With the demand for high-energy-storage devices, the rechargeable metal-oxygen battery has attracted attention recently. Sodium-oxygen batteries have been regarded as the most promising candidates because of their lower-charge overpotential compared with that of lithium-oxygen system. However, conflicting observations with different discharge products have inhibited the understanding of precise reactions in the battery. Here we demonstrate that the competition between the electrochemical and chemical reactions in sodium-oxygen batteries leads to the dissolution and ionization of sodium superoxide, liberating superoxide anion and triggering the formation of sodium peroxide dihydrate (Na2O2.2H2O). On the formation of Na2O2.2H2O, the charge overpotential of sodium oxygen cells significantly increases. This verification addresses the origin of conflicting discharge products and overpotentials observed in sodium-oxygen systems. Our proposed model provides guidelines to help direct the reactions in sodium-oxygen batteries to achieve high efficiency and rechargeability. PMID- 26892932 TI - Can Erythrocyte Catalase Regulate Blood Pressure? AB - This study investigated the effect of antihypertensive therapy with lisinopril on plasma cholesterol concentration and erythrocyte catalase activity in hypertensive patients. We observed, for the first time, significant inverse correlations between systolic blood pressure (BP) and erythrocyte catalase activity and between diastolic BP and erythrocyte catalase activity. Plasma total and low density lipoprotein (LDL) cholesterol as well as triglyceride levels were similar between baseline and 1-, 3-, and 6-month treatment values in the same patients; however, systolic and diastolic BP levels were expectedly reduced after the therapy. Thus, there was no association between BP and lipid-cholesterol metabolism. These findings confirm antihypertensive effect of lisinopril and suggest that erythrocyte catalase is involved in BP control in hypertension and antihypertensive therapy. PMID- 26892933 TI - Increased risk of hepatic complications in kidney transplantation with chronic virus hepatitis infection: A nationwide population-based cohort study. AB - Data regarding the risk of various liver diseases among different hepatitis viruses in kidney transplantation have not yet been identified.We selected individuals with kidney transplantation (ICD-9-CM V420 or 996.81) from 2000-2009 from the catastrophic illness registry of National Health Insurance Research Database (NHIRD)as the study cohort. The two end-points in the study included overall death, and post-transplant occurrence of hepatic disease. After adjustment for other risk factors, the risk of mortality was increased in patients with HBV infection (N = 352) and with HCV infection (N = 275) compared to those with neither HBV nor HCV infection (N = 3485). In addition,renal transplant recipients with HBV alone,HCV alone, and both with HBV and HCVinfectionrespectively had an approximately 10-fold hazard ratio (HR) = 9.84, 95% confidence interval (CI): 4.61-21.0, 4-fold increased risk (HR = 4.40, 95% CI: 1.85-10.5)and 5-fold increased risk (HR = 4.63, 95% CI: 1.06-20.2)of hepatocellular carcinoma (HCC)compared to those with neither HBV nor HCV infection. Our findings showed a significant risk of de novo liver disease in recipients with hepatitis virus infection. Based on our findings, we reinforce the importance and impact of hepatitis virus in renal transplantation. PMID- 26892935 TI - Reticulate acropigmentation of Kitamura with a novel ADAM10 mutation: A case report. PMID- 26892936 TI - A mouse model for hepatitis E virus infection. PMID- 26892934 TI - Balancing selection and recombination as evolutionary forces caused population genetic variations in golden pheasant MHC class I genes. AB - BACKGROUND: The major histocompatibility complex (MHC) genes are vital partners in the acquired immune processes of vertebrates. MHC diversity may be directly associated with population resistance to infectious pathogens. Here, we screened for polymorphisms in exons 2 and 3 of the IA1 and IA2 genes in 12 golden pheasant populations across the Chinese mainland to characterize their genetic variation levels, to understand the effects of historical positive selection and recombination in shaping class I diversity, and to investigate the genetic structure of wild golden pheasant populations. RESULTS: Among 339 individual pheasants, we identified 14 IA1 alleles in exon 2 (IA1-E2), 11 IA1-E3 alleles, 27 IA2-E2 alleles, and 28 IA2-E3 alleles. The non-synonymous substitution rate was significantly greater than the synonymous substitution rate at sequences in the IA2 gene encoding putative peptide-binding sites but not in the IA1 gene; we also found more positively selected sites in IA2 than in IA1. Frequent recombination events resulted in at least 9 recombinant IA2 alleles, in accordance with the intermingling pattern of the phylogenetic tree. Although some IA alleles are widely shared among studied populations, large variation occurs in the number of IA alleles across these populations. Allele frequency analysis across 2 IA loci showed low levels of genetic differentiation among populations on small geographic scales; however, significant genetic differentiation was observed between pheasants from the northern and southern regions of the Yangtze River. Both STRUCTURE analysis and F-statistic (F ST ) value comparison classified those populations into 2 major groups: the northern region of the Yangtze River (NYR) and the southern region of the Yangtze River (SYR). CONCLUSIONS: More extensive polymorphisms in IA2 than IA1 indicate that IA2 has undergone much stronger positive-selection pressure during evolution. Moreover, the recombination events detected between the genes and the intermingled phylogenetic pattern indicate that interlocus recombination accounts for much of the allelic variation in IA2. Analysis of the population differentiation implied that homogenous balancing selection plays an important part in maintaining an even distribution of MHC variations. The natural barrier of the Yangtze River and heterogeneous balancing selection might help shape the NYR-SYR genetic structure in golden pheasants. PMID- 26892937 TI - Can venous base excess replace arterial base excess as a marker of early shock and a predictor of survival in trauma? AB - INTRODUCTION: Arterial base excess is an established marker of shock and predictor of survival in trauma patients. However, venous blood is more quickly and easily obtained. This study aimed to determine if venous base excess could replace arterial base excess as a marker in trauma patients at presentation and if venous base excess is predictive of survival at 24 hours and one week. METHODS: This was a prospective study of 394 trauma patients presenting to the emergency department of a tertiary hospital over a 17-month period. Data on base excess at presentation, vital signs, shock index (SI), injury severity score (ISS), and mortality at 24 hours and one week was collected and analysed. RESULTS: Arterial and venous blood gas tests were performed on 260 and 134 patients, respectively. Patients were stratified into groups based on their SI and ISS for analysis. There was no statistical difference between mean venous blood gas and arterial blood gas levels at presentation when SI > 0.7, regardless of ISS (p > 0.05). The mortality rate was 4.57%. Both venous and arterial base excess was lower in nonsurvivors compared to survivors (p < 0.05). However, at 24 hours and one week, the difference in base excess values at presentation between survivors and nonsurvivors was greater when using venous base excess compared to arterial base excess (11.53 vs. 4.28 and 11.41 vs. 2.66, respectively). CONCLUSION: In conclusion, venous base excess can replace arterial base excess in trauma patients as a means of identifying and prognosticating early shock. PMID- 26892938 TI - Anal HPV/HIV co-infection among Men Who Have Sex with Men: a cross-sectional survey from three cities in China. AB - Anal human papillomavirus (HPV) infection, which is linked to anal warts and anal cancer, is common among men who have sex with men (MSM), especially among those HIV positives. MSM aged 18 years or older were recruited from mainland China. Blood and anal cytologic samples were collected for HIV-1 serological test and HPV genotyping. A total of 889 eligible participations were included. The genotyping results of HPV were available for 822 participants (92.46%), 65.32% of which were positive for the targeted 37 HPV types. Prevalence of infection with any type of HPV was higher among HIV-infected participants (82.69%) as compared to HIV-uninfected participants (62.81%) (p < 0.01). HPV06 (15.45%), HPV18(13.50%), HPV16 (11.44%), and HPV11 (10.71%) were the most frequent types identified in the study population. Ever had paid sex with man was found to be independent predictor for HPV positivity with an adjusted odds ratios (OR) of 2.34 (1.16-4.74). Anal HPV positivity was observed to be independently associated with HIV infection with an adjusted OR of 3.03 (1.76-5.21) in the study population. In conclusion, the prevalence of anal HPV infection was observed to be common among MSM from mainland China, and it was significantly associated with the status of HIV infection. PMID- 26892939 TI - Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial. AB - OBJECTIVE: ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (6* seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.5* seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice. METHOD: This was a pragmatic, patient- and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or high-dose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition. RESULTS: Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=-1.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months. CONCLUSIONS: Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile. PMID- 26892941 TI - Phosphodiesterase 10A in Schizophrenia: A PET Study Using [(11)C]IMA107. AB - OBJECTIVE: Phosphodiesterase 10A (PDE10A) is an enzyme present in striatal medium spiny neurons that degrades the intracellular second messengers triggered by dopamine signaling. The pharmaceutical industry has considerable interest in PDE10A inhibitors because they have been shown to have an antipsychotic-like effect in animal models. However, the status of PDE10A in schizophrenia is unknown. Using a newly developed and validated radioligand, [(11)C]IMA107, the authors report the first in vivo assessment of PDE10A brain expression in patients with schizophrenia. METHOD: The authors compared PDE10A availability in the brains of 12 patients with chronic schizophrenia and 12 matched healthy comparison subjects using [(11)C]IMA107 positron emission tomography (PET). Regional estimates of the binding potential (BPND) of [(11)C]IMA107 were generated from dynamic PET scans using the simplified reference tissue model with the cerebellum as the reference tissue for nonspecific binding. RESULTS: There was no significant difference in [(11)C]IMA107 BPND between schizophrenia patients and comparison subjects in any of the brain regions studied (thalamus, caudate, putamen, nucleus accumbens, globus pallidus, and substantia nigra). There was also no significant correlation between [(11)C]IMA107 BPND and the severity of psychotic symptoms or antipsychotic dosage. CONCLUSIONS: Patients with schizophrenia have normal availability of PDE10A in brain regions thought to be involved in the pathophysiology of this disorder. The findings do not support the proposal of an altered PDE10A availability in schizophrenia. The implication of this finding for future drug development is discussed. PMID- 26892940 TI - Toward the Definition of a Bipolar Prodrome: Dimensional Predictors of Bipolar Spectrum Disorders in At-Risk Youths. AB - OBJECTIVE: The authors sought to assess dimensional symptomatic predictors of new onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths). METHOD: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders. RESULTS: Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion. CONCLUSIONS: Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings. PMID- 26892942 TI - Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders. AB - OBJECTIVE: Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm because such labeling is deficient in both patient groups. The authors hypothesized that during face emotion labeling, irritability would be associated with dysfunctional activation in the amygdala and other temporal and prefrontal regions in both disorders, but that the nature of these associations would differ between DMDD and bipolar disorder. METHOD: During functional MRI acquisition, 71 youths (25 with DMDD, 24 with bipolar disorder, and 22 healthy youths) performed a labeling task with happy, fearful, and angry faces of varying emotional intensity. RESULTS: Participants with DMDD and bipolar disorder showed similar levels of irritability and did not differ from each other or from healthy youths in face emotion labeling accuracy. Irritability correlated with amygdala activity across all intensities for all emotions in the DMDD group; such correlation was present in the bipolar disorder group only for fearful faces. In the ventral visual stream, associations between neural activity and irritability were found more consistently in the DMDD group than in the bipolar disorder group, especially in response to ambiguous angry faces. CONCLUSIONS: These results suggest diagnostic specificity in the neural correlates of irritability, a symptom of both DMDD and bipolar disorder. Such evidence of distinct neural correlates suggests the need to evaluate different approaches to treating irritability in the two disorders. PMID- 26892943 TI - Circumflex coronary artery injury after mitral valve surgery: A report of four cases and comprehensive review of the literature. AB - As the LCx is closely related to the mitral valve annulus, it is susceptible to perioperative injury. Various underlying mechanisms, predisposing factors, and therapeutic strategies have been suggested but disagreement exists. Using a MeSH terms-based PubMed search, 44 cases of mitral valve surgery-related LCx injury were detected, including our 4 cases. We provide a comprehensive review of current knowledge regarding mitral valve surgery-related left circumflex coronary artery (LCx) injury. Preoperative coronary angiography was performed in 55% (n = 24). Coronary abnormalities were present in 11% (n = 5). Coronary dominance was reported in 73% (n = 32), predominantly showing left (69%, n = 22) or balanced (19%, n = 6) circulations. Right coronary dominance was present in 12% (n = 4). Ischemia was detected in the perioperative or early postoperative phase in 86% (n = 30). Delayed symptoms were present in 14% (n = 5). Echocardiography demonstrated new regional wall motion abnormalities in 80% (n = 24), but was negative in 20% (n = 6) despite coronary compromise. Electrocardiography showed myocardial ischemia in 97% (n = 34), including regional ST-segment elevations in 68% (n = 23). Primary treatment was surgical in 42% (n = 15) and percutaneous in 58% (n = 21), reporting success ratios of 87% (n = 13) and 81% (n = 17), respectively. We confirm an augmented risk of mitral valve surgery-related LCx injury in balanced or left-dominant coronary circulations. Preoperative knowledge of coronary anatomy does not preclude LCx injury. An anomalous LCx arising from the right coronary cusp was identified as a possible specific high-risk entity. Electrocardiographic monitoring and intraoperative echocardiography remain paramount to ensure a timely diagnosis and treatment. (c) 2016 Wiley Periodicals, Inc. PMID- 26892944 TI - Prophylaxis and remediation of anomia in the semantic and logopenic variants of primary progressive aphasia. AB - This study evaluated the efficacy of phonological and orthographic treatments for anomia in the semantic and logopenic variants of primary progressive aphasia (svPPA and lvPPA, respectively). Both treatments were administered for 6 months. The treatment stimuli consisted of nouns that were consistently named correctly at baseline (prophylaxis items) and/or nouns that were consistently named incorrectly at baseline (remediation items). Oral naming accuracy was measured for trained and untrained picture exemplars, as well as matched items from an untrained condition (UC). Written naming and scene description tasks were also conducted. For all tasks, the change in naming accuracy from baseline to 1 month post-treatment was compared between the UC and each treatment condition. These comparisons indicated that both treatments were effective in the remediation and prophylaxis of anomia in both variants. Furthermore, generalisation to untrained exemplars occurred in both subtypes, whereas item generalisation occurred in lvPPA, and task generalisation was present in svPPA. PMID- 26892945 TI - In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel. AB - To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p < 0.001) higher for double-contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26892948 TI - Flexible macrocycles as versatile supports for catalytically active metal clusters. AB - Here we present three structurally diverse clusters stabilised by the same macrocyclic polyphenol; t-butylcalix[8]arene. This work demonstrates the range of conformations the flexible ligand is capable of adopting, highlighting its versatility in metal coordination. In addition, a Ti complex displays activity for the ring-opening polymerisation of lactide. PMID- 26892947 TI - Characterization of Supersaturated Danazol Solutions - Impact of Polymers on Solution Properties and Phase Transitions. AB - PURPOSE: Excipients are essential for solubility enhancing formulations. Hence it is important to understand how additives impact key solution properties, particularly when supersaturated solutions are generated by dissolution of the solubility enhancing formulation. Herein, the impact of different concentrations of dissolved polymers on the thermodynamic and kinetic properties of supersaturated solutions of danazol were investigated. METHODS: A variety of experimental techniques was used, including nanoparticle tracking analysis, fluorescence and ultraviolet spectroscopy and flux measurements to characterize the solution phase behavior. RESULTS: Neither the crystalline nor amorphous solubility of danazol was impacted by common amorphous solid dispersion polymers, polyvinylpyrrolidone, hydroxypropylmethyl cellulose (HPMC) or HPMC-acetate succinate. Consequently, the maximum membrane transport rate was limited only by the amorphous solubility, and not by the presence of the polymers. The polymers were able to inhibit crystallization to some extent at concentrations as low as 1 MUg/mL, with the maximum effectiveness being reached at 10 MUg/mL. Aqueous danazol solutions formed a drug-rich phase with a mean size of 250 nm when the concentration exceeded the amorphous solubility, and the polymers modified the surface properties of this drug-rich phase. CONCLUSIONS: The phase behavior of supersaturated solutions is complex and the kinetics of phase transformations can be substantially modified by polymeric additives present at low concentrations. However, fortunately, these additives do not appear to impact the bulk thermodynamic properties of the solution, thus enabling supersaturated solutions, which provide enhanced membrane transport relative to saturated solutions to be generated. PMID- 26892946 TI - Intraoral versus extraoral bitewing radiography in detection of enamel proximal caries: an ex vivo study. AB - OBJECTIVE: To compare the diagnostic accuracy of digital intraoral and extraoral bitewing (EO BW) radiography in the detection of enamel proximal caries regardless of their ability to separate contacts. METHODS: Artificial caries with different degrees of decalcification was induced in 80 human sound premolars and molars using formic acid. Intraoral radiographs were taken with photostimulable phosphor plate (PSP) and complementary metal oxide semiconductor (CMOS), using the paralleling bitewing technique. Extraoral bitewing radiographs were obtained using Sirona digital panoramic X-ray unit (Sirona Siemens, Bensheim, Germany). In total, 160 proximal surfaces were assessed by 2 observers twice. Area under the receiver operating characteristic curve (Az) values for each image type, observer and reading were compared using z-tests, with a significance level of p <= 0.05. Sensitivity, specificity, positive-predictive value and negative-predictive value for each observer and reading were calculated. RESULTS: Spearman's test showed a strong positive correlation between the duration of demineralization and histological grading of carious teeth surfaces. For the three radiographic techniques, intraobserver reliability was strong to excellent. Moreover, interobserver agreement was strong. The differences between all detection methods were not statistically significant (p > 0.05). Intraoral bitewing using CMOS sensor had the highest sensitivity while EO BW had the highest specificity in the detection of incipient proximal caries. CONCLUSIONS: Within the limits of the ex vivo design, the difference in diagnostic accuracy between the three radiographic techniques was not significant. EO BW could be used in the detection of enamel proximal caries with results comparable with intraoral bitewing with PSP plate and CMOS sensor. PMID- 26892949 TI - Survival of a Foal with Type A Botulism. PMID- 26892950 TI - The association between self-perceived health status and satisfaction with healthcare services: Evidence from Armenia. AB - BACKGROUND: Armenians very rarely seek healthcare services and, consequently experience more serious health conditions. With its ongoing reforms, Armenia is focusing on linking health system financing to the quality and volume of care provided. We examine the relationship between the perceived health status of the population and the satisfaction with healthcare services. METHODS: A pooled probit model is applied to analyse three datasets (2010, 2011 and 2012) from the Integrated Living Conditions Survey (ILCS). RESULTS: We find a strong association between self-perceived health and satisfaction with healthcare services but this association is not consistent across regions. CONCLUSIONS: The socioeconomic position of the household alone does not explain the perception of individual health status. The perceived dwelling condition and geography of residence emerged as important stressors on associations between the perceived health status of the population and the satisfaction with healthcare services. We have modelled the perceived health status and satisfaction with the healthcare services using demand side datasets. This study establishes the need to re examine this association in a multidimensional construct. PMID- 26892952 TI - Improving Patient Experience and Primary Care Quality for Patients With Complex Chronic Disease Using the Electronic Patient-Reported Outcomes Tool: Adopting Qualitative Methods Into a User-Centered Design Approach. AB - BACKGROUND: Many mHealth technologies do not meet the needs of patients with complex chronic disease and disabilities (CCDDs) who are among the highest users of health systems worldwide. Furthermore, many of the development methodologies used in the creation of mHealth and eHealth technologies lack the ability to embrace users with CCDD in the specification process. This paper describes how we adopted and modified development techniques to create the electronic Patient Reported Outcomes (ePRO) tool, a patient-centered mHealth solution to help improve primary health care for patients experiencing CCDD. OBJECTIVE: This paper describes the design and development approach, specifically the process of incorporating qualitative research methods into user-centered design approaches to create the ePRO tool. Key lessons learned are offered as a guide for other eHealth and mHealth research and technology developers working with complex patient populations and their primary health care providers. METHODS: Guided by user-centered design principles, interpretive descriptive qualitative research methods were adopted to capture user experiences through interviews and working groups. Consistent with interpretive descriptive methods, an iterative analysis technique was used to generate findings, which were then organized in relation to the tool design and function to help systematically inform modifications to the tool. User feedback captured and analyzed through this method was used to challenge the design and inform the iterative development of the tool. RESULTS: Interviews with primary health care providers (n=7) and content experts (n=6), and four focus groups with patients and carers (n=14) along with a PICK analysis Possible, Implementable, (to be) Challenged, (to be) Killed-guided development of the first prototype. The initial prototype was presented in three design working groups with patients/carers (n=5), providers (n=6), and experts (n=5). Working group findings were broken down into categories of what works and what does not work to inform modifications to the prototype. This latter phase led to a major shift in the purpose and design of the prototype, validating the importance of using iterative codesign processes. CONCLUSIONS: Interpretive descriptive methods allow for an understanding of user experiences of patients with CCDD, their carers, and primary care providers. Qualitative methods help to capture and interpret user needs, and identify contextual barriers and enablers to tool adoption, informing a redesign to better suit the needs of this diverse user group. This study illustrates the value of adopting interpretive descriptive methods into user-centered mHealth tool design and can also serve to inform the design of other eHealth technologies. Our approach is particularly useful in requirements determination when developing for a complex user group and their health care providers. PMID- 26892951 TI - Characterisation of exposure to non-ionising electromagnetic fields in the Spanish INMA birth cohort: study protocol. AB - BACKGROUND: Analysis of the association between exposure to electromagnetic fields of non-ionising radiation (EMF-NIR) and health in children and adolescents is hindered by the limited availability of data, mainly due to the difficulties on the exposure assessment. This study protocol describes the methodologies used for characterising exposure of children to EMF-NIR in the INMA (INfancia y Medio Ambiente- Environment and Childhood) Project, a prospective cohort study. METHODS/DESIGN: Indirect (proximity to emission sources, questionnaires on sources use and geospatial propagation models) and direct methods (spot and fixed longer-term measurements and personal measurements) were conducted in order to assess exposure levels of study participants aged between 7 and 18 years old. The methodology used varies depending on the frequency of the EMF-NIR and the environment (homes, schools and parks). Questionnaires assessed the use of sources contributing both to Extremely Low Frequency (ELF) and Radiofrequency (RF) exposure levels. Geospatial propagation models (NISMap) are implemented and validated for environmental outdoor sources of RFs using spot measurements. Spot and fixed longer-term ELF and RF measurements were done in the environments where children spend most of the time. Moreover, personal measurements were taken in order to assess individual exposure to RF. The exposure data are used to explore their relationships with proximity and/or use of EMF-NIR sources. DISCUSSION: Characterisation of the EMF-NIR exposure by this combination of methods is intended to overcome problems encountered in other research. The assessment of exposure of INMA cohort children and adolescents living in different regions of Spain to the full frequency range of EMF-NIR extends the characterisation of environmental exposures in this cohort. Together with other data obtained in the project, on socioeconomic and family characteristics and development of the children and adolescents, this will enable to evaluate the complex interaction between health outcomes in children and adolescents and the various environmental factors that surround them. PMID- 26892954 TI - Digital Breast Tomosynthesis: A Brave New World of Mammography Screening. PMID- 26892953 TI - Color stability of recent composite resins. AB - The objective of the study was to evaluate the color stability of 8 recently developed resin composites when exposed to various staining agents. Six disc shaped specimens made out of 8 resin composite materials were immersed in artificial saliva, coffee, coke, tea, orange juice and red wine. The initial color (T0) of the 288 specimens was assessed by a calibrated reflectance spectrophotometer (SpectroShade, MHT) over a black as well as a white background. All specimens were kept in an incubator (INP-500, Memmert GmbH) at 37 degrees C for 4 weeks. Colorant solutions were changed every 7 days to avoid bacteria or yeast contamination. After 4 weeks of storage in the colorants (T1), spectrophotometric measurements were repeated and DeltaE00 was calculated. When analyzed over a white background, the mean DeltaE00 values varied from 1.5 (Venus Diamond) to 52.4 (Miris 2). When analyzed over a black background, the mean DeltaE00 values varied from 0.8 (Venus Diamond) to 40.0 (ELS). Significant differences were detected when comparing values at T0 and T1 (DeltaE00) for both backgrounds (Anova and Fisher's LSD post hoc test). Resin composite materials do behave in a significantly different way (p value < 0.01) when exposed to various staining solutions. PMID- 26892955 TI - Atherosclerosis: Successes, Surprises, and Future Challenges. PMID- 26892956 TI - Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease. AB - Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic. PMID- 26892957 TI - Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology. AB - Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2 fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality. PMID- 26892958 TI - Genetics of Coronary Artery Disease. AB - Genetic factors contribute importantly to the risk of coronary artery disease (CAD), and in the past decade, there has been major progress in this area. The tools applied include genome-wide association studies encompassing >200,000 individuals complemented by bioinformatic approaches, including 1000 Genomes imputation, expression quantitative trait locus analyses, and interrogation of Encyclopedia of DNA Elements, Roadmap, and other data sets. close to 60 common SNPs (minor allele frequency>0.05) associated with CAD risk and reaching genome wide significance (P<5 * 10(-8)) have been identified. Furthermore, a total of 202 independent signals in 109 loci have achieved a false discovery rate (q<0.05) and together explain 28% of the estimated heritability of CAD. These data have been used successfully to create genetic risk scores that can improve risk prediction beyond conventional risk factors and identify those individuals who will benefit most from statin therapy. Such information also has important applications in clinical medicine and drug discovery by using a Mendelian randomization approach to interrogate the causal nature of many factors found to associate with CAD risk in epidemiological studies. In contrast to genome-wide association studies, whole-exome sequencing has provided valuable information directly relevant to genes with known roles in plasma lipoprotein metabolism but has, thus far, failed to identify other rare coding variants linked to CAD. Overall, recent studies have led to a broader understanding of the genetic architecture of CAD and demonstrate that it largely derives from the cumulative effect of multiple common risk alleles individually of small effect size rather than rare variants with large effects on CAD risk. Despite this success, there has been limited progress in understanding the function of the novel loci; the majority of which are in noncoding regions of the genome. PMID- 26892959 TI - Surprises From Genetic Analyses of Lipid Risk Factors for Atherosclerosis. AB - Observational epidemiological studies have associated plasma lipid concentrations with risk for coronary heart disease (CHD), but these studies cannot distinguish cause from mere correlation. Human genetic studies, when considered with the results of randomized controlled trials of medications, can potentially shed light on whether lipid biomarkers are causal for diseases. Genetic analyses and randomized trials suggest that low-density lipoprotein is causal for CHD, whereas high-density lipoprotein is not. Surprisingly, human genetic evidence suggests that lipoprotein(a) and triglyceride-rich lipoproteins causally contribute to CHD. Gene variants leading to higher levels of plasma apolipoprotein B-containing lipoproteins [low-density lipoprotein, triglyceride-rich lipoproteins, or lipoprotein(a)] consistently increase risk for CHD. For triglyceride-rich lipoproteins, the most compelling evidence revolves around lipoprotein lipase and its endogenous facilitator (APOA5 [apolipoprotein A-V]) and inhibitory proteins (APOC3 [apolipoprotein C-III], ANGPTL4 [angiopoietin like 4]). Combined, these genetic results anticipate that, beyond low-density lipoprotein, pharmacological lowering of triglyceride-rich lipoproteins or lipoprotein(a) will reduce risk for CHD, but this remains to be proven through randomized controlled trials. PMID- 26892961 TI - Are Genetic Tests for Atherosclerosis Ready for Routine Clinical Use? AB - In this review, we lay out 3 areas currently being evaluated for incorporation of genetic information into clinical practice related to atherosclerosis. The first, familial hypercholesterolemia, is the clearest case for utility of genetic testing in diagnosis and potentially guiding treatment. Already in use for confirmatory testing of familial hypercholesterolemia and for cascade screening of relatives, genetic testing is likely to expand to help establish diagnoses and facilitate research related to most effective therapies, including new agents, such as PCSK9 inhibitors. The second area, adding genetic information to cardiovascular risk prediction for primary prevention, is not currently recommended. Although identification of additional variants may add substantially to prediction in the future, combining known variants has not yet demonstrated sufficient improvement in prediction for incorporation into commonly used risk scores. The third area, pharmacogenetics, has utility for some therapies today. Future utility for pharmacogenetics will wax or wane depending on the nature of available drugs and therapeutic strategies. PMID- 26892963 TI - Macrophages and Dendritic Cells: Partners in Atherogenesis. AB - Atherosclerosis is a complex chronic disease. The accumulation of myeloid cells in the arterial intima, including macrophages and dendritic cells (DCs), is a feature of early stages of disease. For decades, it has been known that monocyte recruitment to the intima contributes to the burden of lesion macrophages. Yet, this paradigm may require reevaluation in light of recent advances in understanding of tissue macrophage ontogeny, their capacity for self-renewal, as well as observations that macrophages proliferate throughout atherogenesis and that self-renewal is critical for maintenance of macrophages in advanced lesions. The rate of atherosclerotic lesion formation is profoundly influenced by innate and adaptive immunity, which can be regulated locally within atherosclerotic lesions, as well as in secondary lymphoid organs, the bone marrow and the blood. DCs are important modulators of immunity. Advances in the past decade have cemented our understanding of DC subsets, functions, hematopoietic origin, gene expression patterns, transcription factors critical for differentiation, and provided new tools for study of DC biology. The functions of macrophages and DCs overlap to some extent, thus it is important to reassess the contributions of each of these myeloid cells taking into account strict criteria of cell identification, ontogeny, and determine whether their key roles are within atherosclerotic lesions or secondary lymphoid organs. This review will highlight key aspect of macrophage and DC biology, summarize how these cells participate in different stages of atherogenesis and comment on complexities, controversies, and gaps in knowledge in the field. PMID- 26892960 TI - From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease. AB - Genome-wide association studies have provided a rich collection of ~ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD. PMID- 26892965 TI - Adaptive Response of T and B Cells in Atherosclerosis. AB - Atherosclerosis is a chronic inflammatory disease that is initiated by the retention and accumulation of cholesterol-containing lipoproteins, particularly low-density lipoprotein, in the artery wall. In the arterial intima, lipoprotein components that are generated through oxidative, lipolytic, and proteolytic activities lead to the formation of several danger-associated molecular patterns, which can activate innate immune cells as well as vascular cells. Moreover, self- and non-self-antigens, such as apolipoprotein B-100 and heat shock proteins, can contribute to vascular inflammation by triggering the response of T and B cells locally. This process can influence the initiation, progression, and stability of plaques. Substantial clinical and experimental data support that the modulation of adaptive immune system may be used for treating and preventing atherosclerosis. This may lead to the development of more selective and less harmful interventions, while keeping host defense mechanisms against infections and tumors intact. Approaches such as vaccination might become a realistic option for cardiovascular disease, especially if they can elicit regulatory T and B cells and the secretion of atheroprotective antibodies. Nevertheless, difficulties in translating certain experimental data into new clinical therapies remain a challenge. In this review, we discuss important studies on the function of T- and B-cell immunity in atherosclerosis and their manipulation to develop novel therapeutic strategies against cardiovascular disease. PMID- 26892962 TI - Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. AB - Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment. PMID- 26892964 TI - Macrophage Phenotype and Function in Different Stages of Atherosclerosis. AB - The remarkable plasticity and plethora of biological functions performed by macrophages have enticed scientists to study these cells in relation to atherosclerosis for >50 years, and major discoveries continue to be made today. It is now understood that macrophages play important roles in all stages of atherosclerosis, from initiation of lesions and lesion expansion, to necrosis leading to rupture and the clinical manifestations of atherosclerosis, to resolution and regression of atherosclerotic lesions. Lesional macrophages are derived primarily from blood monocytes, although recent research has shown that lesional macrophage-like cells can also be derived from smooth muscle cells. Lesional macrophages take on different phenotypes depending on their environment and which intracellular signaling pathways are activated. Rather than a few distinct populations of macrophages, the phenotype of the lesional macrophage is more complex and likely changes during the different phases of atherosclerosis and with the extent of lipid and cholesterol loading, activation by a plethora of receptors, and metabolic state of the cells. These different phenotypes allow the macrophage to engulf lipids, dead cells, and other substances perceived as danger signals; efflux cholesterol to high-density lipoprotein; proliferate and migrate; undergo apoptosis and death; and secrete a large number of inflammatory and proresolving molecules. This review article, part of the Compendium on Atherosclerosis, discusses recent advances in our understanding of lesional macrophage phenotype and function in different stages of atherosclerosis. With the increasing understanding of the roles of lesional macrophages, new research areas and treatment strategies are beginning to emerge. PMID- 26892969 TI - The Success Story of LDL Cholesterol Lowering. AB - We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. PMID- 26892966 TI - Microdomains, Inflammation, and Atherosclerosis. AB - Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1-mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic alpha-helix-rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation. PMID- 26892967 TI - Vascular Smooth Muscle Cells in Atherosclerosis. AB - The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis. PMID- 26892970 TI - From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk. AB - The introduction of statins ~ 30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of therapeutics targeted to lipids and atherosclerosis has entered a renaissance. Moreover, the demonstration of clinical benefits from the addition of ezetimibe to statin therapy in subjects with acute coronary syndromes has renewed the enthusiasm for the cholesterol hypothesis and the hope that additional agents that lower low-density lipoprotein will decrease risk of atherosclerotic cardiovascular disease. Drugs in the orphan disease category are now available for patients with the most extreme hypercholesterolemia. Furthermore, discovery and rapid translation of a novel biological pathway has given rise to a new class of cholesterol-lowering drugs, the proprotein convertase subtilisin kexin-9 inhibitors. Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels. Although the utility of triglyceride-lowering therapies remains uncertain, 2 large clinical trials are testing the influence of omega-3 polyunsaturated fatty acids on atherosclerotic events in hypertriglyceridemia. Novel antisense therapies targeting apolipoprotein C-III (for triglyceride reduction) and apo(a) (for lipoprotein(a) reduction) are showing a promising trajectory. Finally, 2 large clinical trials are formally putting the inflammatory hypothesis of atherosclerosis to the test and may open a new avenue for cardiovascular disease risk reduction. PMID- 26892968 TI - MicroRNA Regulation of Atherosclerosis. AB - Atherosclerosis and its attendant clinical complications, such as myocardial infarction, stroke, and peripheral artery disease, are the leading cause of morbidity and mortality in Western societies. In response to biochemical and biomechanical stimuli, atherosclerotic lesion formation occurs from the participation of a range of cell types, inflammatory mediators, and shear stress. Over the past decade, microRNAs (miRNAs) have emerged as evolutionarily conserved, noncoding small RNAs that serve as important regulators and fine tuners of a range of pathophysiological cellular effects and molecular signaling pathways involved in atherosclerosis. Accumulating studies reveal the importance of miRNAs in regulating key signaling and lipid homeostasis pathways that alter the balance of atherosclerotic plaque progression and regression. In this review, we highlight current paradigms of miRNA-mediated effects in atherosclerosis progression and regression. We provide an update on the potential use of miRNAs diagnostically for detecting increasing severity of coronary disease and clinical events. Finally, we provide a perspective on therapeutic opportunities and challenges for miRNA delivery in the field. PMID- 26892972 TI - Trastuzumab Emtansine for Treating HER2-Positive, Unresectable, Locally Advanced or Metastatic Breast Cancer After Treatment with Trastuzumab and a Taxane: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. AB - The National Institute for Health and Care Excellence (NICE) invited the manufacturer of trastuzumab emtansine (T-DM1) (Kadcyla((r)); Roche) to submit evidence of its clinical and cost-effectiveness for treating human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced or metastatic breast cancer after treatment with trastuzumab and a taxane. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield were the independent Evidence Review Group (ERG) who produced a critical review of the company's submission to NICE. The ERG also independently searched for relevant evidence and modified the submitted decision analytic model to produce a revised estimate of cost-effectiveness and examine the impact of altering some of the key assumptions. The clinical effectiveness data were taken from two randomised controlled trials that reported a significant advantage in progression-free survival (PFS) for T-DM1 over lapatinib in combination with capecitabine (EMILIA trial), and over the treatment of physician's choice (TH3RESA trial). A network meta-analysis suggested T-DM1 was the best treatment in terms of both overall survival and PFS compared with lapatinib in combination with capecitabine; trastuzumab in combination with capecitabine; and capecitabine monotherapy. Adverse event (AE) data were taken from a pooled analysis of additional trials of T-DM1 as a single agent. The most common grade 3 or greater AEs for T-DM1 were thrombocytopenia and hepatotoxicity. Following the clarification process, the manufacturer reported a deterministic incremental cost-effectiveness ratio (ICER) for T-DM1 compared with lapatinib in combination with capecitabine of L167,236, the latter of which was estimated to have an ICER of L49,798 compared with capecitabine monotherapy. The ERG produced similar values of L166,429 and L50,620 respectively. All other comparators were dominated. During the appraisal, the manufacturer offered an analysis of a patient access scheme (PAS), which suggested that T-DM1 had a 0 % probability of being cost-effective at an ICER of L30,000 per QALY gained. The NICE Appraisal Committee concluded that while the clinical effectiveness of T-DM1 had been proven, it was not likely to represent a cost-effective use of National Health Service resources and therefore its use could not be recommended. PMID- 26892973 TI - Health, Health-Related Quality of Life, and Quality of Life: What is the Difference? AB - The terms health, health-related quality of life (HRQoL), and quality of life (QoL) are used interchangeably. Given that these are three key terms in the literature, their appropriate and clear use is important. This paper reviews the history and definitions of the terms and considers how they have been used. It is argued that the definitions of HRQoL in the literature are problematic because some definitions fail to distinguish between HRQoL and health or between HRQoL and QoL. Many so-called HRQoL questionnaires actually measure self-perceived health status and the use of the phrase QoL is unjustified. It is concluded that the concept of HRQoL as used now is confusing. A potential solution is to define HRQoL as the way health is empirically estimated to affect QoL or use the term to only signify the utility associated with a health state. PMID- 26892974 TI - Ledipasvir-Sofosbuvir for Treating Chronic Hepatitis C: A NICE Single Technology Appraisal-An Evidence Review Group Perspective. AB - The National Institute for Health and Care Excellence (NICE) invited Gilead, the company manufacturing ledipasvir-sofosbuvir (LDV/SOF), to submit evidence for the clinical effectiveness and cost effectiveness of LDV/SOF for treating chronic hepatitis C. The School of Health and Related Research (ScHARR) Technology Assessment Group was commissioned as the Evidence Review Group (ERG). This paper describes the company's submission (CS), the ERG review and the subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical effectiveness and cost-effectiveness evidence of LDV/SOF based upon the CS. The clinical effectiveness data for LDV/SOF were taken from ten trials: three phase III trials and seven phase II trials. Trials compared different durations of LDV/SOF, with and without ribavirin (RBV). There were no head-to-head trials comparing LDV/SOF with any comparator listed in the NICE scope. Data from the trials were mostly from populations with genotype 1 (GT1) disease, although some limited data were available for populations with genotypes 3 and 4. For GT1 treatment-naive patients, sustained viral response for 12 weeks (SVR12) rates for LDV/SOF ranged from 93.1 to 99.4 % for subgroups of patients with non-cirrhotic disease, whilst SVR rates of 94.1 to 100 % were reported for subgroups of patients with compensated cirrhosis. For GT1 treatment-experienced patients, SVR12 rates ranging from 95.4 to 100 % were reported for subgroups of non-cirrhotic patients, and SVR rates ranging from 81.8 to 100 % were reported within subgroups of patients with compensated cirrhosis. Comparator data were not searched systematically as part of the submission, but were based on the company's previous NICE submission of sofosbuvir, with additional targeted searches. The ERG's critical appraisal of the company's economic evaluation highlighted a number of concerns. The ERG's base case analyses suggested that the incremental cost-effectiveness ratios (ICERs) for LDV/SOF (+RBV) are dependent on (a) treatment durations, (b) whether patients have been previously treated and (c) whether patients have liver cirrhosis or not. The AC concluded that it was appropriate to use the approach taken in the ERG's exploratory analyses, in line with the marketing authorisation, which considered people with and without cirrhosis separately, and estimated the cost effectiveness for each recommended treatment duration of LDV/SOF. PMID- 26892976 TI - Using built-in functions of Adobe Acrobat Pro DC to help the selection process in systematic reviews of randomised trials. AB - This letter describes a simple way of using Adobe Acrobat Pro DC to help select and auto-extract data from Portable Document Format (PDFs) of randomised trials in order to assist swift early selection of trials for a systematic review. PMID- 26892978 TI - Correction. AB - Saxena A, Mehta A, Ramakrishnan S, et al. Pulse oximetry as a screening tool for detecting major congenital heart defects in Indian newborns (Arch Dis Child Fetal Neonatal Ed 2015;100:F416-21). The authors have pointed out that there was an error in figure 1. The original figure 1 shows a saturation cut off of 92%. However, the authors later revised the figure to show a cut off to 95% but this one was not used. The correct figure is now published. PMID- 26892975 TI - Use of Heart Failure Medical Therapies Among Patients With Left Ventricular Assist Devices: Insights From INTERMACS. AB - BACKGROUND: Use of left ventricular assist devices (LVADs) for treatment of advanced heart failure has expanded significantly over the past decade. However, concomitant use of heart failure medical therapies after implant is poorly characterized. METHODS AND RESULTS: We examined the use of heart failure medications before and after LVAD implant in adult patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) between 2008 and 2013 (N = 9359). Using logistic regression, we examined relationships between patient characteristics and medication use at 3 months after implant. Baseline rates of heart failure therapies before implant were 38% for angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), 55% for beta-blockers, 40% for mineralocorticoid receptor antagonists (MRAs), 87% for loop diuretics, 54% for amiodarone, 11% for phosphodiesterase inhibitors, 22% for warfarin, and 54% for antiplatelet agents. By 3 months after implant, the rates were 50% for ACE inhibitors or ARBs, 68% for beta-blockers, 33% for MRAs, 68% for loop diuretics, 42% for amiodarone, 21% for phosphodiesterase inhibitors, 92% for warfarin, and 84% for antiplatelet agents. In general, age, preimplant INTERMACS profile, and prior medication use were associated with medication use at 3 months. CONCLUSIONS: Overall use of neurohormonal antagonists was low after LVAD implant, whereas use of loop diuretics and amiodarone remained high. Heart failure medication use is highly variable, but appears to generally increase after LVAD implantation. Low neurohormonal antagonist use may reflect practice uncertainty in the clinical utility of these medications post-LVAD. PMID- 26892971 TI - Imaging Atherosclerosis. AB - Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic. PMID- 26892977 TI - The effect of amyotrophic lateral sclerosis-linked exogenous SOD1-G93A on electrophysiological properties and intracellular calcium in cultured rat astrocytes. AB - Over 150 mutations in the SOD1 gene that encodes Cu/Zn superoxide dismutase (SOD1) cause 20-25% of familial ALS, albeit without a known gain-of-function mechanism. ALS is also non-cell-autonomous, the interactions between motor neurons and their glial neighbours being implicated in disease progression. The aim here was to investigate the biophysical effects of the exogenous human mutant SOD1-G93A on rat astrocytes in culture. Primary cortical astrocyte cultures were treated with recombinant human apo- mSOD1-G93A vs. wild-type control (wtSOD1) and recorded by patch-clamp and calcium imaging. Results showed that exogenous mSOD1 as well as wtSOD1 induced a decrease of membrane resistance, the effect being persistent (up to 13 min) only for the mutant form. Similarly, whole-cell inward currents in astrocytes were augmented by both wt and mSOD1, but the effect was twice larger and only progressed continuously for the latter. Both forms of SOD1 also induced a rise in intracellular Ca(2+) activity, the effect being dependent on external Ca(2+) and again only persisted with mSOD1, becoming significantly different from wtSOD1 only at longer times (14 min). In conclusion, this study points to membrane permeability and Ca(2+) signalling as processes affected by SOD1-G93A that presents the humoral factor triggering the role of astrocytes in ALS pathophysiology. PMID- 26892979 TI - Expert consensus statement to guide the evidence-based classification of Paralympic athletes with vision impairment: a Delphi study. AB - BACKGROUND: Paralympic sports are required to develop evidence-based systems that allocate athletes into 'classes' on the basis of the impact of their impairment on sport performance. However, sports for athletes with vision impairment (VI) classify athletes solely based on the WHO criteria for low vision and blindness. One key barrier to evidence-based classification is the absence of guidance on how to address classification issues unique to VI sport. The aim of this study was to reach expert consensus on how issues specific to VI sport should be addressed in evidence-based classification. METHOD: A four-round Delphi study was conducted with 25 participants who had expertise as a coach, athlete, classifier and/or administrator in Paralympic sport for VI athletes. RESULTS: The experts agreed that the current method of classification does not fulfil the requirements of Paralympic classification, and that the system should be different for each sport to account for the sports' unique visual demands. Instead of relying only on tests of visual acuity and visual field, the panel agreed that additional tests are required to better account for the impact of impairment on sport performance. There was strong agreement that all athletes should not be required to wear a blindfold as a means of equalising the impairment during competition. CONCLUSIONS: There is strong support within the Paralympic movement to change the way that VI athletes are classified. This consensus statement provides clear guidance on how the most important issues specific to VI should be addressed, removing key barriers to the development of evidence-based classification. PMID- 26892981 TI - BMI, body fat and waist-to-height ratio of stunted v. non-stunted Indian children: a case-control study. AB - OBJECTIVE: To compare the BMI, body fat and waist-to-height ratio (WHtR) of stunted and non-stunted children following different growth trajectories from low socio-economic strata in Mumbai, India. DESIGN: Cross-sectional, case-control study. Weight, height, skinfold thicknesses and waist circumference were measured. Information regarding the duration of breast-feeding, age at initiation of complementary feeding and income was obtained. Birth weight was obtained from records. BMI, body fat, WHtR and change in weight sd were calculated. SETTING: Children who were beneficiaries of anganwadis, Mumbai city, India. SUBJECTS: Three hundred and thirty children aged 2-4 years were selected in each of the stunted and non-stunted groups after matching for age and sex. RESULTS: After adjusting for birth weight, change in weight sd, duration of breast-feeding, age at complementary feeding initiation and income, stunted children had significantly higher body fat, WHtR and BMI than the non-stunted (P<0.01). The stunted and non-stunted children were classified based on their change in weight sd. Stunted children with no change in weight sd had higher mean body fat, BMI (P<0.01) and WHtR (P<0.05) than their non-stunted counterparts. In the catch-up growth group, stunted children had higher BMI and WHtR than the non-stunted (both P<0.001). In the catch-down growth group, stunted children had higher BMI than the non-stunted (P<0.001). CONCLUSIONS: Stunting was seen to increase the tendency of conserving body fat in young children. Such a tendency, if continued during later childhood and adolescence, can increase the risk of obesity and non communicable diseases. PMID- 26892980 TI - Genetic variation frequencies in Wilms' tumor: A meta-analysis and systematic review. AB - Over the last few decades, numerous biomarkers in Wilms' tumor have been confirmed and shown variations in prevalence. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published from 1992 to 2015 to obtain more precise and comprehensive outcomes for genetic tests. In the present study, 70 out of 5175 published reports were eligible for the meta analysis, which was carried out using Stata 12.0 software. Pooled prevalence for gene mutations WT1, WTX, CTNNB1, TP53, MYCN, DROSHA, and DGCR8 was 0.141 (0.104, 0.178), 0.147 (0.110, 0.184), 0.140 (0.100, 0.190), 0.410 (0.214, 0.605), 0.071 (0.041, 0.100), 0.082 (0.048, 0.116), and 0.036 (0.026, 0.046), respectively. Pooled prevalence of loss of heterozygosity at 1p, 11p, 11q, 16q, and 22q was 0.109 (0.084, 0.133), 0.334 (0.295, 0.373), 0.199 (0.146, 0.252), 0.151 (0.129, 0.172), and 0.148 (0.108, 0.189), respectively. Pooled prevalence of 1q and chromosome 12 gain was 0.218 (0.161, 0.275) and 0.273 (0.195, 0.350), respectively. The limited prevalence of currently known genetic alterations in Wilms' tumors indicates that significant drivers of initiation and progression remain to be discovered. Subgroup analyses indicated that ethnicity may be one of the sources of heterogeneity. However, in meta-regression analyses, no study level characteristics of indicators were found to be significant. In addition, the findings of our sensitivity analysis and possible publication bias remind us to interpret results with caution. PMID- 26892983 TI - Autoimmune Comorbidities Are Associated with Brain Injury in Multiple Sclerosis. AB - BACKGROUND AND PURPOSE: The effect of comorbidities on disease severity in MS has not been extensively characterized. We determined the association of comorbidities with MR imaging disease severity outcomes in MS. MATERIALS AND METHODS: Demographic and clinical history of 9 autoimmune comorbidities confirmed by retrospective chart review and quantitative MR imaging data were obtained in 815 patients with MS. The patients were categorized on the basis of the presence/absence of total and specific comorbidities. We analyzed the MR imaging findings, adjusting for key covariates and correcting for multiple comparisons. RESULTS: Two hundred forty-one (29.6%) study subjects presented with comorbidities. Thyroid disease had the highest frequency (n = 97, 11.9%), followed by asthma (n = 41, 5%), type 2 diabetes mellitus (n = 40, 4.9%), psoriasis (n = 33, 4%), and rheumatoid arthritis (n = 22, 2.7%). Patients with MS with comorbidities showed decreased whole-brain and cortical volumes (P < .001), gray matter volume and magnetization transfer ratio of normal-appearing brain tissue (P < .01), and magnetization transfer ratio of gray matter (P < .05). Psoriasis, thyroid disease, and type 2 diabetes mellitus comorbidities were associated with decreased whole-brain, cortical, and gray matter volumes (P < .05). Psoriasis was associated with a decreased magnetization transfer ratio of normal-appearing brain tissue (P < .05), while type 2 diabetes mellitus was associated with increased mean diffusivity (P < .01). CONCLUSIONS: The presence of comorbidities in patients with MS is associated with brain injury on MR imaging. Psoriasis, thyroid disease, and type 2 diabetes mellitus comorbidities were associated with more severe nonconventional MR imaging outcomes. PMID- 26892984 TI - Inflow Jet Patterns of Unruptured Cerebral Aneurysms Based on the Flow Velocity in the Parent Artery: Evaluation Using 4D Flow MRI. AB - BACKGROUND AND PURPOSE: Inflow jet characteristics may be related to aneurysmal bleb formation and rupture. We investigated the visualization threshold on the basis of the flow velocity in the parent artery to classify the inflow jet patterns observed on 4D flow MR imaging. MATERIALS AND METHODS: Fifty-seven unruptured aneurysms (24 bifurcation and 33 sidewall aneurysms) were subjected to 4D flow MR imaging to visualize inflow streamline bundles whose velocity exceeded visualization thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery. The shape of the streamline bundle was determined visually, and the inflow jet patterns were classified as concentrated, diffuse, neck-limited, and unvisualized. RESULTS: At the 75% threshold, bifurcation aneurysms exhibited a concentrated inflow jet pattern at the highest rate. At this threshold, the inflow jets were concentrated in 13 aneurysms (group C, 22.8%), diffuse in 18 (group D, 31.6%), neck-limited in 11 (group N, 19.3%), and unvisualized in 15 (group U, 26.3%). In 16 (28.1%) of the 57 aneurysms, the inflow jet pattern was different at various thresholds. Most inflow parameters, including the maximum inflow velocity and rate, the inflow velocity ratio, and the inflow rate ratio, were significantly higher in groups C and D than in groups N and U. CONCLUSIONS: The inflow jet pattern may depend on the threshold applied to visualize the inflow streamlines on 4D flow MR imaging. For the classification of the inflow jet patterns on 4D flow MR imaging, the 75% threshold may be optimal among the 3 thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery. PMID- 26892985 TI - Imaging of Neurovascular Compression Syndromes: Trigeminal Neuralgia, Hemifacial Spasm, Vestibular Paroxysmia, and Glossopharyngeal Neuralgia. AB - Neurovascular compression syndromes are usually caused by arteries that directly contact the cisternal portion of a cranial nerve. Not all cases of neurovascular contact are clinically symptomatic. The transition zone between the central and peripheral myelin is the most vulnerable region for symptomatic neurovascular compression syndromes. Trigeminal neuralgia (cranial nerve V) has an incidence of 4-20/100,000, a transition zone of 4 mm, with symptomatic neurovascular compression typically proximal. Hemifacial spasm (cranial nerve VII) has an incidence of 1/100,000, a transition zone of 2.5 mm, with symptomatic neurovascular compression typically proximal. Vestibular paroxysmia (cranial nerve VIII) has an unknown incidence, a transition zone of 11 mm, with symptomatic neurovascular compression typically at the internal auditory canal. Glossopharyngeal neuralgia (cranial nerve IX) has an incidence of 0.5/100,000, a transition zone of 1.5 mm, with symptomatic neurovascular compression typically proximal. The transition zone overlaps the root entry zone close to the brain stem in cranial nerves V, VII, and IX, yet it is more distal and does not overlap the root entry zone in cranial nerve VIII. Although symptomatic neurovascular compression syndromes may also occur if the neurovascular contact is outside the transition zone, symptomatic neurovascular compression syndromes are more common if the neurovascular contact occurs at the transition zone or central myelin section, in particular when associated with nerve displacement and atrophy. PMID- 26892982 TI - Training Guidelines for Endovascular Ischemic Stroke Intervention: An International Multi-Society Consensus Document. PMID- 26892986 TI - Thinner Regions of Intracranial Aneurysm Wall Correlate with Regions of Higher Wall Shear Stress: A 7T MRI Study. AB - BACKGROUND AND PURPOSE: Both hemodynamics and aneurysm wall thickness are important parameters in aneurysm pathophysiology. Our aim was to develop a method for semi-quantitative wall thickness assessment on in vivo 7T MR images of intracranial aneurysms for studying the relation between apparent aneurysm wall thickness and wall shear stress. MATERIALS AND METHODS: Wall thickness was analyzed in 11 unruptured aneurysms in 9 patients who underwent 7T MR imaging with a TSE-based vessel wall sequence (0.8-mm isotropic resolution). A custom analysis program determined the in vivo aneurysm wall intensities, which were normalized to the signal of nearby brain tissue and were used as measures of apparent wall thickness. Spatial wall thickness variation was determined as the interquartile range in apparent wall thickness (the middle 50% of the apparent wall thickness range). Wall shear stress was determined by using phase-contrast MR imaging (0.5-mm isotropic resolution). We performed visual and statistical comparisons (Pearson correlation) to study the relation between wall thickness and wall shear stress. RESULTS: 3D colored apparent wall thickness maps of the aneurysms showed spatial apparent wall thickness variation, which ranged from 0.07 to 0.53, with a mean variation of 0.22 (a variation of 1.0 roughly means a wall thickness variation of 1 voxel [0.8 mm]). In all aneurysms, apparent wall thickness was inversely related to wall shear stress (mean correlation coefficient, -0.35; P < .05). CONCLUSIONS: A method was developed to measure the wall thickness semi-quantitatively, by using 7T MR imaging. An inverse correlation between wall shear stress and apparent wall thickness was determined. In future studies, this noninvasive method can be used to assess spatial wall thickness variation in relation to pathophysiologic processes such as aneurysm growth and rupture. PMID- 26892987 TI - C-Arm Conebeam CT Perfusion Imaging in the Angiographic Suite: A Comparison with Multidetector CT Perfusion Imaging. AB - BACKGROUND AND PURPOSE: Perfusion imaging in the angiography suite may provide a way to reduce time from stroke onset to endovascular revascularization of patients with large-vessel occlusion. Our purpose was to compare conebeam CT perfusion with multidetector CT perfusion. MATERIALS AND METHODS: Data from 7 subjects with both multidetector CT perfusion and conebeam CT perfusion were retrospectively processed and analyzed. Two algorithms were used to enhance temporal resolution and temporal sampling density and reduce the noise of conebeam CT data before generating perfusion maps. Two readers performed qualitative image-quality evaluation on maps by using a 5-point scale. ROIs indicating CBF/CBV abnormalities were drawn. Quantitative analyses were performed by using the Sorensen-Dice coefficients to quantify the similarity of abnormalities. A noninferiority hypothesis was tested to compare conebeam CT perfusion against multidetector CT perfusion. RESULTS: Average image-quality scores for multidetector CT perfusion and conebeam CT perfusion images were 2.4 and 2.3, respectively. The average confidence score in diagnosis was 1.4 for both multidetector CT and conebeam CT; the average confidence scores for the presence of a CBV/CBF mismatch were 1.7 (kappa = 0.50) and 1.5 (kappa = 0.64). For multidetector CT perfusion and conebeam CT perfusion maps, the average scores of confidence in making treatment decisions were 1.4 (kappa = 0.79) and 1.3 (kappa = 0.90). The area under the visual grading characteristic for the above 4 qualitative quality scores showed an average area under visual grading characteristic of 0.50, with 95% confidence level cover centered at the mean for both readers. The Sorensen-Dice coefficient for CBF maps was 0.81, and for CBV maps, 0.55. CONCLUSIONS: After postprocessing methods were applied to enhance image quality for conebeam CT perfusion maps, the conebeam CT perfusion maps were not inferior to those generated from multidetector CT perfusion. PMID- 26892988 TI - Computer-Assisted Detection of Cerebral Aneurysms in MR Angiography in a Routine Image-Reading Environment: Effects on Diagnosis by Radiologists. AB - BACKGROUND AND PURPOSE: Experiences with computer-assisted detection of cerebral aneurysms in diagnosis by radiologists in real-life clinical environments have not been reported. The purpose of this study was to evaluate the usefulness of computer-assisted detection in a routine reading environment. MATERIALS AND METHODS: During 39 months in a routine clinical practice environment, 2701 MR angiograms were each read by 2 radiologists by using a computer-assisted detection system. Initial interpretation was independently made without using the detection system, followed by a possible alteration of diagnosis after referring to the lesion candidate output from the system. We used the final consensus of the 2 radiologists as the reference standard. The sensitivity and specificity of radiologists before and after seeing the lesion candidates were evaluated by aneurysm- and patient-based analyses. RESULTS: The use of the computer-assisted detection system increased the number of detected aneurysms by 9.3% (from 258 to 282). Aneurysm-based analysis revealed that the apparent sensitivity of the radiologists' diagnoses made without and with the detection system was 64% and 69%, respectively. The detection system presented 82% of the aneurysms. The detection system more frequently benefited radiologists than being detrimental. CONCLUSIONS: Routine integration of computer-assisted detection with MR angiography for cerebral aneurysms is feasible, and radiologists can detect a number of additional cerebral aneurysms by using the detection system without a substantial decrease in their specificity. The low confidence of radiologists in the system may limit its usefulness. PMID- 26892989 TI - Acoustic resolution photoacoustic Doppler velocimetry in blood-mimicking fluids. AB - Photoacoustic Doppler velocimetry provides a major opportunity to overcome limitations of existing blood flow measuring methods. By enabling measurements with high spatial resolution several millimetres deep in tissue, it could probe microvascular blood flow abnormalities characteristic of many different diseases. Although previous work has demonstrated feasibility in solid phantoms, measurements in blood have proved significantly more challenging. This difficulty is commonly attributed to the requirement that the absorber spatial distribution is heterogeneous relative to the minimum detectable acoustic wavelength. By undertaking a rigorous study using blood-mimicking fluid suspensions of 3 MUm absorbing microspheres, it was discovered that the perceived heterogeneity is not only limited by the intrinsic detector bandwidth; in addition, bandlimiting due to spatial averaging within the detector field-of-view also reduces perceived heterogeneity and compromises velocity measurement accuracy. These detrimental effects were found to be mitigated by high-pass filtering to select photoacoustic signal components associated with high heterogeneity. Measurement under-reading due to limited light penetration into the flow vessel was also observed. Accurate average velocity measurements were recovered using "range-gating", which furthermore maps the cross-sectional velocity profile. These insights may help pave the way to deep-tissue non-invasive mapping of microvascular blood flow using photoacoustic methods. PMID- 26892990 TI - Screening Out Controversy: Human Genetics, Emerging Techniques of Diagnosis, and the Origins of the Social Issues Committee of the American Society of Human Genetics, 1964-1973. AB - In the years following World War II, and increasingly during the 1960s and 1970s, professional scientific societies developed internal sub-committees to address the social implications of their scientific expertise (Moore, Disrupting Science: Social Movements, American Scientists, and the Politics of the Military, 1945 1975. Princeton: Princeton University Press, 2008). This article explores the early years of one such committee, the American Society of Human Genetics' "Social Issues Committee," founded in 1967. Although the committee's name might suggest it was founded to increase the ASHG's public and policy engagement, exploration of the committee's early years reveals a more complicated reality. Affronted by legislators' recent unwillingness to seek the expert advice of human geneticists before adopting widespread neonatal screening programs for phenylketonuria (PKU), and feeling pressed to establish their relevance in an increasingly resource-scarce funding environment, committee members sought to increase the discipline's expert authority. Painfully aware of controversy over abortion rights and haunted by the taint of the discipline's eugenic past, however, the committee proceeded with great caution. Seeking to harness interest in and assert professional control over emerging techniques of genetic diagnosis, the committee strove to protect the society's image by relegating ethical and policy questions about their use to the individual consciences of member scientists. It was not until 1973, after the committee's modest success in organizing support for a retrospective public health study of PKU screening and following the legalization of abortion on demand, that the committee decided to take a more publicly engaged stance. PMID- 26892991 TI - Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. AB - BACKGROUND: Human papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood. OBJECTIVES: To determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN: We included 1711 women (18-25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS: Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were -5.4% (95% confidence interval -19,10) and 0.3% (95% confidence interval -69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval -131, 82) and -211% (95% confidence interval -2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval -43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively. CONCLUSION: We find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies. PMID- 26892995 TI - New Cholesterol Guidelines for the Management of Atherosclerotic Cardiovascular Disease Risk: A Comparison of the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines with the 2014 National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia. AB - This review discusses the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and compares it with the 2014 National Lipid Association (NLA) Recommendations for Patient-Centered Management of Dyslipidemia. The review discusses some of the distinctions between the guidelines, including how to determine a patient's atherosclerotic cardiovascular disease risk, the role of lipoprotein treatment targets, the importance of moderate- and high-intensity statin therapy, and the use of nonstatin therapy in light of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial. PMID- 26892994 TI - Familial Hypercholesterolemia. AB - Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder. PMID- 26892993 TI - Ultrasonography reveals in vivo dose-dependent inhibition of end systolic and diastolic volumes, heart rate and cardiac output by nesfatin-1 in zebrafish. AB - Nesfatin-1 is an 82 amino acid peptide that inhibits food intake in rodents and fish. While endogenous nesfatin-1, and its role in the regulation of food intake and hormone secretion has been reported in fish, information on cardiovascular functions of nesfatin-1 in fish is in its infancy. We hypothesized that cardiac NUCB2 expression is meal responsive and nesfatin-1 is a cardioregulatory peptide in zebrafish. NUCB2/nesfatin-1 like immunoreactivity was detected in zebrafish cardiomyocytes. Real-time quantitative PCR analysis found that the cardiac expression of NUCB2A mRNA in unfed fish decreased at 1h post-regular feeding time. Food deprivation for 7days did not change NUCB2A mRNA expression. However, NUCB2B mRNA expression was increased in the heart of zebrafish after a 7-day food deprivation. Ultrasonography of zebrafish heart at 15min post-intraperitoneal injection of nesfatin-1 (250 and 500ng/g body weight) showed a dose-dependent inhibition of end diastolic and end systolic volumes. A dose dependent decrease in heart rate and cardiac output was observed in zebrafish that received nesfatin 1, but no changes in stroke volume were found. Nesfatin-1 treatment caused a significant increase in the expression of Atp2a2a mRNA encoding the calcium handling pump, SERCA2a, while it had no effects on the expression of calcium handling protein RyR1b encoding mRNA. Our data support cardiosuppressive effects of nesfatin-1 in zebrafish, and reveals energy availability as one determinant of cardiac NUCB2 mRNA expression. PMID- 26892996 TI - Lipoprotein Apheresis. AB - Patients with familial hypercholesterolemia (FH) have early development of atherosclerosis and cardiovascular disease (CVD). Lipid level-lowering medications are not always successful in reducing increased low-density lipoprotein C (LDL-C) levels. Lipoprotein apheresis (LA) therapy has proven its clinical benefit in reducing CVD events for patients with FH with hypercholesterolemia. LA reduces LDL-C levels by more than 60% in patients with FH and reduces CVD events. LA also reduces Lp(a) levels and CVD events. LA reduces inflammatory markers and blood viscosity. PMID- 26892992 TI - Mesenchymal stem cells promote colorectal cancer progression through AMPK/mTOR mediated NF-kappaB activation. AB - Mesenchymal stem cells (MSCs) exert a tumor-promoting effect in a variety of human cancers. This study was designed to identify the molecular mechanisms related to the tumor-promoting effect of MSCs in colorectal cancer. In vitro analysis of colorectal cancer cell lines cultured in MSC conditioned media (MSC CM) showed that MSC-CM significantly promoted the progression of the cancer cells by enhancing cell proliferation, migration and colony formation. The tumorigenic effect of MSC-CM was attributed to altered expression of cell cycle regulatory proteins and inhibition of apoptosis. Furthermore, MSC-CM induced high level expression of a number of pluripotency factors in the cancer cells. ELISAs revealed MSC-CM contained higher levels of IL-6 and IL-8, which are associated with the progression of cancer. Moreover, MSC-CM downregulated AMPK mRNA and protein phosphorylation, but upregulated mTOR mRNA and protein phosphorylation. The NF-kappaB pathway was activated after addition of MSC-CM. An in vivo model in Balb/C mice confirmed the ability of MSC-CM to promote the invasion and proliferation of colorectal cancer cells. This study indicates that MSCs promote the progression of colorectal cancer via AMPK/mTOR-mediated NF-kappaB activation. PMID- 26892997 TI - Dyslipidemia in Pregnancy. AB - "Recent studies have revealed evidence that poorly controlled cholesterol, triglycerides, and their metabolites during pregnancy may be associated with cardiometabolic dysfunction and have significant detrimental fetal and maternal vascular consequences. Cardiometabolic dysfunction during pregnancy may not only contribute to long-term effects of the mother and child's vascular health but also potentially create cardiovascular risk for generational offspring. This article provides updates on this rapidly expanding and multifaceted topic and reviews new insight regarding why recognition of this disordered maternal cholesterol and triglyceride metabolism is likely to have long-term effect on the increasing atherosclerotic burden of the burgeoning population." PMID- 26892998 TI - Women's Health Considerations for Lipid Management. AB - Understanding opportunities to reduce dyslipidemia before, during, and after pregnancy has major implications for cardiovascular disease risk prevention for the entire population. The best time to screen for dyslipidemia is before pregnancy or in the early antenatal period. The differential diagnosis of hypertriglyceridemia in pregnancy is the same as in nonpregnant women except that clinical lipidologists need to be aware of the potential obstetric complications associated with hypertriglyceridemia. Dyslipidemia discovered during pregnancy should be treated with diet and exercise intervention, as well as glycemic control if indicated. A complete lipid profile assessment during each trimester of pregnancy is recommended. PMID- 26892999 TI - Statins and Diabetes. AB - A statin is first-line drug therapy for dyslipidemia. Clinical trial data suggest there is an increase in the incidence of new-onset type 2 diabetes mellitus with statin use. The National Lipid Association (NLA) Statin Diabetes Safety Task Force concluded that the cardiovascular benefit of statin therapy outweighs the risk for developing diabetes. The NLA panel advocated following the standards of care from the American Diabetes Association for screening and diagnosis of diabetes, and emphasized the importance of lifestyle modification. This article summarizes NLA's review of the evidence, expanding it to include recent results, and outlines the clinical recommendations. PMID- 26893000 TI - Statins and Cognitive Side Effects: What Cardiologists Need to Know. AB - Statins are widely used in secondary and primary prevention of atherosclerotic cardiovascular disease. They reduce cardiovascular events and mortality, and have an excellent safety record. Recent case reports suggest a possible association between statins and adverse effects on cognition. This article reviews recent literature related to statins and cognition and provides recommendations to clinicians. Cognitive considerations should not play a role in decision making for most patients for whom statins are indicated. Future trials of statin, or any novel antilipemic agent should include systematic assessment of cognition. PMID- 26893001 TI - Statins and the Liver. AB - Lipid lowering, particularly with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ("statins"), reduces the risk of cardiovascular disease. Patients with chronic liver disease present challenges to the use of lipid medications. In the case of most liver disorders, the concern has been one of safety. There is evidence that most lipid-lowering medications can be used safely in many situations, although large outcomes trials are lacking. This review examines lipid physiology and cardiovascular risk in specific liver diseases and reviews the evidence for lipid lowering and the use of statins in chronic liver disease. PMID- 26893002 TI - Genetic Testing in Hyperlipidemia. AB - Hereditary dyslipidemias are often underdiagnosed and undertreated, yet with significant health implications, most importantly causing preventable premature cardiovascular diseases. The commonly used clinical criteria to diagnose hereditary lipid disorders are specific but are not very sensitive. Genetic testing may be of value in making accurate diagnosis and improving cascade screening of family members, and potentially, in risk assessment and choice of therapy. This review focuses on using genetic testing in the clinical setting for lipid disorders, particularly familial hypercholesterolemia. PMID- 26893003 TI - Lipid Management in Human Immunodeficiency Virus. AB - The development and use of antiretroviral medications to treat patients infected with human immunodeficiency virus (HIV) has dramatically changed the course of this disease from one that was fatal to a chronic and more manageable condition. Recommendations and guidelines for the general population are presented in this review with suggestions as to how they may be applied to this patient population. Issues for which there is little or no information available are noted to highlight the many gaps in our knowledge regarding diagnosis and management of dyslipidemia for patients living with HIV. PMID- 26893004 TI - Managing Residual Risk After Myocardial Infarction Among Individuals with Low Cholesterol Levels. AB - About one-half of individuals with an acute myocardial infarction have a low density lipoprotein cholesterol level of less than 100 mg/dL at the time of occurrence, but remain at risk for recurrent events. This residual risk is likely mediated by multiple factors, including burden of atherosclerosis, residual dyslipidemia, nonlipid risk factors, and suboptimal implementation of lifestyle therapy and evidence-based pharmacologic therapy. This article reviews management options for this high-risk population. PMID- 26893005 TI - Management of Hypertriglyceridemia for Prevention of Atherosclerotic Cardiovascular Disease. AB - Mendelian randomization data strongly suggest that hypertriglyceridemia (HTG) causes atherosclerotic cardiovascular disease (ASCVD), and so triglyceride (TG) level-lowering treatment in HTG is now more strongly recommended to address the residual ASCVD risk than has been the case in (generally earlier) published guidelines. Fibrates are the best-established agents for TG level lowering and are generally used as first-line treatment of TG levels greater than 500 mg/dL. Statins are the best-established agents for ASCVD prevention, and so are usually used as first-line treatment of TG levels less than 500 mg/dL. PMID- 26893006 TI - Dyslipidemia in Special Ethnic Populations. AB - This article reviews racial/ethnic differences in dyslipidemia-prevalence of dyslipidemia, its relation to coronary heart disease (CHD) and stroke mortality rates, response to lipid-lowering agents, and lifestyle modification. Asian Indians, Filipinos, and Hispanics are at higher risk for dyslipidemia, which is consistent with the higher CHD mortality rates in these groups. Statins may have greater efficacy for Asians, but the data are mixed. Lifestyle modifications are recommended. Culturally-tailored prevention and intervention should be provided to the minority populations with elevated risk for dyslipidemia and considerably more research is needed to determine the best approaches to helping specific subgroups. PMID- 26893007 TI - Development and validation of a questionnaire evaluating patient anxiety during Magnetic Resonance Imaging: the Magnetic Resonance Imaging-Anxiety Questionnaire (MRI-AQ). AB - AIM: To develop and validate a new instrument measuring patient anxiety during Magnetic Resonance Imaging examinations, Magnetic Resonance Imaging- Anxiety Questionnaire. BACKGROUND: Questionnaires measuring patients' anxiety during Magnetic Resonance Imaging examinations have been the same as used in a wide range of conditions. To learn about patients' experience during examination and to evaluate interventions, a specific questionnaire measuring patient anxiety during Magnetic Resonance Imaging is needed. DESIGN: Psychometric cross-sectional study with test-retest design. METHODS: A new questionnaire, Magnetic Resonance Imaging-Anxiety Questionnaire, was designed from patient expressions of anxiety in Magnetic Resonance Imaging-scanners. The sample was recruited between October 2012-October 2014. Factor structure was evaluated with exploratory factor analysis and internal consistency with Cronbach's alpha. Criterion-related validity, known-group validity and test-retest was calculated. RESULTS: Patients referred for Magnetic Resonance Imaging of either the spine or the heart, were invited to participate. The development and validation of Magnetic Resonance Imaging-Anxiety Questionnaire resulted in 15 items consisting of two factors. Cronbach's alpha was found to be high. Magnetic Resonance Imaging-Anxiety Questionnaire correlated higher with instruments measuring anxiety than with depression scales. Known-group validity demonstrated a higher level of anxiety for patients undergoing Magnetic Resonance Imaging scan of the heart than for those examining the spine. Test-retest reliability demonstrated acceptable level for the scale. CONCLUSION: Magnetic Resonance Imaging-Anxiety Questionnaire bridges a gap among existing questionnaires, making it a simple and useful tool for measuring patient anxiety during Magnetic Resonance Imaging examinations. PMID- 26893008 TI - Social and psychological challenges remain after obstetric fistula repair. PMID- 26893009 TI - [Body dysmorphic disorder : Anxiety about deformity]. AB - Between 0.8 and 1.8 % of the German population suffers from a body dysmorphic disorder. In specific settings like dermatological offices up to 11.9 % of patients suffer from this disease. The highest prevalence could be found in the field of cosmetic dermatology with a prevalence of 13.1 %. Until now, the diagnosis has been made too rarely. The body dysmorphic disorder is a chronic psychic disease, in which the patients feel disfigured and experience shame and disgust at the same time. Comorbidities like social phobia, depression, suicidality, and eating disorders are frequent. The diagnosis is made using questionnaires (e.g., dysmorphic concern questionnaire) or by use of the DSM-5 manual. An early diagnosis seems to be important to avoid chronification and suicidal ideas. Therapeutic approaches should include cognitive behavioral therapies as well as the use of SSRIs. PMID- 26893010 TI - Development of indicators to assess the quality of medicines reconciliation at hospital admission: an e-Delphi study. AB - OBJECTIVE: The aim of this Delphi study was to examine consensus on the appropriateness of the medicines reconciliation (MR) indicators. METHODS: Practising hospital pharmacists in UK hospitals conducting MR in hospital wards were invited to participate in the study. Appropriateness was defined using four criteria: clarity, importance, relevance and usefulness. The modified Delphi technique was selected as a structured method to develop consensus. RAND definition for consensus was used. In the second round, feedback on the first round was provided. The study did not require Research Ethics approval. KEY FINDINGS: Sixty-five hospital pharmacists completed the first round Delphi, and 59 of them completed the second round. Their experience ranged from three to 33 years with an average of 16.6 years. Fifty-five indicators were sent to the panel after the pilot study. Each of the two rounds took approximately 8 weeks to be completed. Forty-one indicators reached consensus to be appropriate. Fourteen indicators did not reach consensus. CONCLUSIONS: The Delphi technique was very effective for enhancing the panel participation as noticed in their responses both in the first and second rounds. Forty-one indicators achieved consensus as being appropriate to evaluate the MR process. These indicators could be used to assess the process and hence improve the quality of the patient care on hospital admission. The indicators need to be used in practice. PMID- 26893011 TI - Early weaning is beneficial to prevent atopic dermatitis occurrence in young children. AB - BACKGROUND: Epidemiological data on infant feeding practices and allergic diseases are controversial. The purpose of this study was to explore the association of early weaning with the occurrence of atopic dermatitis (AD). METHODS: We conducted a matched case-control study on incident physician diagnosed AD in early childhood including 451 cases and 451 controls. Data on several factors, including feeding practices, were collected through an interviewer-administered questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were estimated through logistic regression models, conditioned on study center, age, sex, and period of interview, and adjusted for potential confounders. RESULTS: Early weaning, defined as the introduction of solid foods at 4 or 5 months of age, was inversely related to the risk of AD, with children weaned at 4 months having lower AD risk (OR = 0.41, 95% CI, 0.20 0.87) compared to those exclusively breastfed. Similar results were observed for weaning started at 5 months of age (OR = 0.39, 95% CI, 0.18-0.83). This association persisted when children with and without family history of allergy were considered separately. Prolonged partial breastfeeding (breastmilk plus milk formulas) was not associated with AD. Consistently, the introduction of a high number of different solid foods reduced the risk of AD (P trend = 0.02 at 4 months of age and P trend = 0.04 at 5 months). CONCLUSION: Our data provide evidence against the preventing role of prolonged exclusive (but not partial) breastfeeding in AD occurrence and confirm recent results indicating a beneficial role of early weaning in AD. PMID- 26893012 TI - Incremental impact upon malaria transmission of supplementing pyrethroid impregnated long-lasting insecticidal nets with indoor residual spraying using pyrethroids or the organophosphate, pirimiphos methyl. AB - BACKGROUND: Long-lasting, insecticidal nets (LLINs) and indoor residual spraying (IRS) are the most widely accepted and applied malaria vector control methods. However, evidence that incremental impact is achieved when they are combined remains limited and inconsistent. METHODS: Fourteen population clusters of approximately 1000 residents each in Zambia's Luangwa and Nyimba districts, which had high pre-existing usage rates (81.7 %) of pyrethroid-impregnated LLINs were quasi-randomly assigned to receive IRS with either of two pyrethroids, namely deltamethrin [Wetable granules (WG)] and lambdacyhalothrin [capsule suspension (CS)], with an emulsifiable concentrate (EC) or CS formulation of the organophosphate pirimiphos methyl (PM), or with no supplementary vector control measure. Diagnostic positivity of patients tested for malaria by community health workers in these clusters was surveyed longitudinally over pre- and post treatment periods spanning 29 months, over which the treatments were allocated and re-allocated in advance of three sequential rainy seasons. RESULTS: Supplementation of LLINs with PM CS offered the greatest initial level of protection against malaria in the first 3 months of application (incremental protective efficacy (IPE) [95 % confidence interval (CI)] = 0.63 [CI 0.57, 0.69], P < 0.001), followed by lambdacyhalothrin (IPE [95 % CI] = 0.31 [0.10, 0.47], P = 0.006) and PM EC (IPE, 0.23 [CI 0.15, 0.31], P < 0.001) and then by deltamethrin (IPE [95 % CI] = 0.19 [-0.01, 0.35], P = 0.064). Neither pyrethroid formulation provided protection beyond 3 months after spraying, but the protection provided by both PM formulations persisted undiminished for longer periods: 6 months for CS and 12 months for EC. The CS formulation of PM provided greater protection than the combined pyrethroid IRS formulations throughout its effective life IPE [95 % CI] = 0.79 [0.75, 0.83] over 6 months. The EC formulation of PM provided incremental protection for the first 3 months (IPE [95 % CI] = 0.23 [0.15, 0.31]) that was approximately equivalent to the two pyrethroid formulations (lambdacyhalothrin, IPE [95 % CI] = 0.31 [0.10, 0.47] and deltamethrin, IPE [95 % CI] = 0.19 [-0.01, 0.35]) but the additional protection provided by the former, apparently lasted an entire year. CONCLUSION: Where universal coverage targets for LLIN utilization has been achieved, supplementing LLINs with IRS using pyrethroids may reduce malaria transmission below levels achieved by LLIN use alone, even in settings where pyrethroid resistance occurs in the vector population. However, far greater reduction of transmission can be achieved under such conditions by supplementing LLINs with IRS using non-pyrethroid insecticide classes, such as organophosphates, so this is a viable approach to mitigating and managing pyrethroid resistance. PMID- 26893014 TI - Effects of home and education environments on children's motor performance in China. AB - AIM: The aim of this study was to examine the effects of home and educational environments on children's motor performance in China. METHOD: We conducted a cross-sectional study of 4001 preschool children selected from 160 classes. The children's motor performance was assessed using the Movement Assessment Battery for Children, 2nd edition (MABC-2). Home and educational environments were evaluated using validated checklists. The effects of home and educational environments on motor performance were analysed using mixed and multilevel logistic regression models. RESULTS: The results showed that one score increase in the outside space of the family home was positively associated with the increase in total test score (0.104) subtest score of aiming and catching (0.037), and balance (0.034) of the MABC-2, after adjusting for potential confounders (each p<0.05). Possession of motor toys at home and parental rearing behaviours were also related to total test score, manual dexterity, and balance (beta=0.022-0.104, each p<0.05). Space and furnishings, activity, and interaction in the classroom had a significant positive association with total test score (beta=0.069-0.201), and with subtest scores of manual dexterity, aiming and catching, and balance respectively (beta=0.115-0.206). Space and furnishings of classrooms and possession of toys in the household were protective factors for 'at risk' or significant poor performance (odds ratio 0.942-0.973, each p<0.05). INTERPRETATION: A permissive and accepting family and educational environment made a positive contribution to children's motor performance. Access to sufficient space and furnishings within the classroom, as well as toys in the family, were protective factors for poor motor performance. Future assistance is needed to support an advantageous environment in early childhood programmes in China. PMID- 26893013 TI - The milk-derived hexapeptide PGPIPN inhibits the invasion and migration of human ovarian cancer cells by regulating the expression of MTA1 and NM23H1 genes. AB - Some bioactive peptides derived from natural resources or synthesized by rational design have been proved to have very good anticancer effect. We studied the inhibition of PGPIPN, a hexapeptide derived from bovine beta-casein, on the invasion and metastasis of human ovarian cancer cells in vitro and its molecular mechanism. The human ovarian cancer cells studied include the cell line SKOV3 as well as the primary ovarian cancer cells from ovarian tumor tissues of 37 patients at initial debulking surgery, diagnosed as serous ovarian adenocarcinoma. We showed that PGPIPN inhibited the invasion of ovarian cancer cells with Transwell chamber assay, the migration of ovarian cancer cells with cell scratch assay and colony formation of ovarian cancer cells. The expression (mRNAs and proteins) of genes relevant to invasion and metastasis, MTA1, and NM23H1 were analyzed by real-time PCR and western blotting. PGPIPN repressed the expression of MTA1, and promoted NM23H1. The effects of PGPIPN were dose dependent. Thus, our study suggests that PGPIPN is a potential therapeutic agent for adjuvant therapy of human malignant ovarian tumors. PMID- 26893017 TI - Propofol for Treatment of Refractory Alcohol Withdrawal Syndrome: A Review of the Literature. AB - The authors evaluated all available evidence on the use of propofol as an adjuvant for the treatment of resistant alcohol withdrawal syndrome (AWS) in comparison to other therapies. A comprehensive PubMed search (1966-December 2015) was conducted using the search terms propofol, alcohol withdrawal, and drug therapy. Articles were cross-referenced for other citations. Clinical studies, case series, and case reports published in the English language assessing the use of propofol in adult patients for treatment of AWS were reviewed for inclusion. Propofol is a sedative-hypnotic that exerts its actions through agonism of GABAA receptors at a different binding site than benzodiazepines and reduces glutamatergic activity through N-methyl-d-aspartase (NMDA) receptor blockade. Dosages from 5 to 100 MUg/kg/minute reduced AWS symptoms with frequent development of hypotension and requirement for mechanical ventilation. Patients on propofol often experienced longer durations of mechanical ventilation and length of stay, which may be attributed to more-resistant cases of AWS. When propofol was compared with dexmedetomidine as adjuncts in AWS, both agents showed similar benzodiazepine- and haloperidol-sparing effects. Dexmedetomidine was associated with more numerical rates of bradycardia, while propofol was associated with more numerical instances of hypotension. Dexmedetomidine was used more frequently in nonintubated patients. The available data assessing the utility of propofol for AWS exhibited significant heterogeneity. Propofol may be useful in a specific population of patients with AWS, limited to those who are not clinically responding to first-line therapy with benzodiazepines. Specifically, propofol should be considered in patients who are refractory to or not candidates for other adjuvant therapies, patients already requiring mechanical ventilation, or those with seizure activity or refractory delirium tremens. In severe, refractory AWS, adjuvant therapy with propofol may be considered but requires further research to recommend its use either preferentially or as monotherapy. PMID- 26893018 TI - Modified radiofrequency ablation for the treatment of hepatocellular carcinoma. AB - AIM: Radiofrequency ablation is commonly used for the treatment of early hepatocellular carcinoma. However, it requires time to ablate sufficient areas, resulting in increased burden for the patients and operators. We introduce a novel and simple method to overcome this problem. METHODS: We placed the grounding pad on the back (Back group) instead of the thigh of the patient (Thigh group). To assess the effect of this method, we randomly assigned the patients into two groups, based on the location of the grounding pad, and compared the outcomes. RESULTS: The ablation time until two roll-offs was shorter in the Back group than in the Thigh group (median, 2.5 min vs 3.4 min; P = 0.01). The ablated area was larger in the Back group than that in the Thigh group (P = 0.01) and pain was less in the Back group (P = 0.02). No severe side-effects were observed in either group. CONCLUSION: This new method is useful in that it achieved shorter ablation times, expansion of the ablated areas, and reduction of pain during the ablation. PMID- 26893016 TI - Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross sectional study of women with benign breast disease. AB - BACKGROUND: Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. METHODS: Serum IGF I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. RESULTS: Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and <0.0001, respectively); these associations were strongest among women with elevated mammographic density (P-interaction <0.01). Circulating IGF levels were not significantly associated with TDLU span or acini count per TDLU. CONCLUSIONS: These results suggest that elevated IGF levels may define a sub-group of women with high mammographic density and limited TDLU involution, two markers that have been related to increased breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system. PMID- 26893019 TI - Late regulation of immune genes and microRNAs in circulating leukocytes in a pig model of influenza A (H1N2) infection. AB - MicroRNAs (miRNAs) are a class of short regulatory RNA molecules which are implicated in modulating gene expression. Levels of circulating, cell-associated miRNAs in response to influenza A virus (IAV) infection has received limited attention so far. To further understand the temporal dynamics and biological implications of miRNA regulation in circulating leukocytes, we collected blood samples before and after (1, 3, and 14 days) IAV challenge of pigs. Differential expression of miRNAs and innate immune factor mRNA transcripts was analysed using RT-qPCR. A total of 20 miRNAs were regulated after IAV challenge, with the highest number of regulated miRNAs seen on day 14 after infection at which time the infection was cleared. Targets of the regulated miRNAs included genes involved in apoptosis and cell cycle regulation. Significant regulation of both miRNAs and mRNA transcripts at 14 days after challenge points to a protracted effect of IAV infection, potentially affecting the host's ability to respond to secondary infections. In conclusion, experimental IAV infection of pigs demonstrated the dynamic nature of miRNA and mRNA regulation in circulating leukocytes during and after infection, and revealed the need for further investigation of the potential immunosuppressing effect of miRNA and innate immune signaling after IAV infection. PMID- 26893021 TI - Fast automated dual-syringe based dispersive liquid-liquid microextraction coupled with gas chromatography-mass spectrometry for the determination of polycyclic aromatic hydrocarbons in environmental water samples. AB - An automated procedure, combining low density solvent based solvent demulsification dispersive liquid-liquid microextraction (DLLME) with gas chromatography-mass spectrometry analysis, was developed for the determination of polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. Capitalizing on a two-rail commercial autosampler, fast solvent transfer using a large volume syringe dedicated to the DLLME process, and convenient extract collection using a small volume microsyringe for better GC performance were enabled. Extraction parameters including the type and volume of extraction solvent, the type and volume of dispersive solvent and demulsification solvent, extraction and demulsification time, and the speed of solvent injection were investigated and optimized. Under the optimized conditions, the linearity ranged from 0.1 to 50 MUg/L, 0.2 to 50 MUg/L, and 0.5 to 50 MUg/L, depending on the analytes. Limits of detection were determined to be between 0.023 and 0.058 MUg/L. The method was applied to determine PAHs in environmental water samples. PMID- 26893020 TI - The relationship between hypertension and health-related quality of life: adjusted by chronic pain, chronic diseases, and life habits in the general middle aged population in Japan. AB - OBJECTIVES: The aim of this study was to examine the relationship between hypertension and health-related quality of life (HRQoL) adjusted by chronic pain, other chronic diseases, and life habits in the general middle-aged population in Japan. METHODS: This study is a population-based cross-sectional study. In this study, 1117 participants aged 40-65 years and living in Shika Town completed a self-administered questionnaire including Short Form-36 (SF-36). The scores of SF 36 among hypertensives were compared with those of normotensives. The independent association of hypertension with each SF-36 subscale was analyzed using a multiple linear regression model adjusted by age, BMI, chronic pain, chronic diseases, sleep, exercise, and occupational status. We analyzed two groups; Group 1 which contained 846 participants completed the questionnaire without coronary heart disease and cerebral vascular disease, Group 2 which contained 686 participants without coronary heart disease, cerebral vascular disease, or diseases accompanied by chronic pain (gastroduodenal ulcer, fracture, osteoarthritis, osteoporosis, rheumatoid arthritis, and disc herniation). RESULTS: In Group 2, hypertensive women had a lower general health perception than normotensive women [unstandardized coefficients; B = -8.84, 95 % confidence interval (95 % CI) = -13.3 to -4.34, standardized coefficients; beta = -0.200, p < 0.001], whereas hypertensive men had higher social functioning than normotensive men (B = 5.66, 95 % CI = 1.30-10.0, beta = 0.149, p < 0.05) after adjusting by chronic pain and life habits. CONCLUSIONS: These results may be due to the sex difference in the light of the perception for health. PMID- 26893022 TI - A liquid chromatography-mass spectrometric method for the detection of cyclic beta-amino fatty acid lipopeptides. AB - Bacterial lipopeptides, which contain beta-amino fatty acids, are an abundant group of bacterial secondary metabolites exhibiting antifungal and/or cytotoxic properties. Here we have developed an LC-HRMS/MS method for the selective detection of beta-amino fatty acid containing cyclic lipopeptides. The method was optimized using the lipopeptides iturin A and puwainaphycin F, which contain fatty acids of similar length but differ in the amino acid composition of the peptide cycle. Fragmentation energies of 10-55eV were used to obtain the amino acid composition of the peptide macrocycle. However, fragmentation energies of 90 130eV were used to obtain an intense fragment specific for the beta-amino fatty acid (CnH2n+2N(+)). The method allowed the number of carbons and consequently the length of the beta-amino fatty acid to be estimated. We identified 21 puwainaphycin variants differing in fatty acid chain in the crude extract of cyanobacterium Cylindrospermum alatosporum using this method. Analogously 11 iturin A variants were detected. The retention time of the lipopeptide variants showed a near perfect linear dependence (R(2)=0.9995) on the length of the fatty acid chain in linear separation gradient which simplified the detection of minor variants. We used the method to screen 240 cyanobacterial strains and identified lipopeptides from 8 strains. The HPLC-HRMS/MS method developed here provides a rapid and easy way to detecting novel variants of cyclic lipopeptides. PMID- 26893023 TI - Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines. AB - A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2 Nitrophenylhydrazine hydrochloride (2-NPH.HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of alpha-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH.HCl using 1-ethyl-3-(3 dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 MUg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue determination of the six HCAs in eight drug substance samples. PMID- 26893025 TI - Self-arrangement of nanoparticles toward crystalline metal oxides with high surface areas and tunable 3D mesopores. AB - We demonstrate a new design concept where the interaction between silica nanoparticles (about 1.5 nm in diameter) with titania nanoparticles (anatase, about 4 nm or 6 nm in diameter) guides a successful formation of mesoporous titania with crystalline walls and controllable porosity. At an appropriate solution pH (~1.5, depending on the deprotonation tendencies of two types of nanoparticles), the smaller silica nanoparticles, which attach to the surface of the larger titania nanoparticles and provide a portion of inactive surface and reactive surface of titania nanoparticles, dictate the direction and the degree of condensation of the titania nanoparticles, resulting in a porous 3D framework. Further crystallization by a hydrothermal treatment and subsequent removal of silica nanoparticles result in a mesoporous titania with highly crystalline walls and tunable mesopore sizes. A simple control of the Si/Ti ratio verified the versatility of the present method through the successful control of mean pore diameter in the range of 2-35 nm and specific surface area in the ranges of 180 250 m(2) g(-1). The present synthesis method is successfully extended to other metal oxides, their mixed oxides and analogues with different particle sizes, regarding as a general method for mesoporous metal (or mixed metal) oxides. PMID- 26893024 TI - Microfluidic Screening of Electric Fields for Electroporation. AB - Electroporation is commonly used to deliver molecules such as drugs, proteins, and/or DNA into cells, but the mechanism remains poorly understood. In this work a rapid microfluidic assay was developed to determine the critical electric field threshold required for inducing bacterial electroporation. The microfluidic device was designed to have a bilaterally converging channel to amplify the electric field to magnitudes sufficient to induce electroporation. The bacterial cells are introduced into the channel in the presence of SYTOX((r)), which fluorescently labels cells with compromised membranes. Upon delivery of an electric pulse, the cells fluoresce due to transmembrane influx of SYTOX((r)) after disruption of the cell membranes. We calculate the critical electric field by capturing the location within the channel of the increase in fluorescence intensity after electroporation. Bacterial strains with industrial and therapeutic relevance such as Escherichia coli BL21 (3.65 +/- 0.09 kV/cm), Corynebacterium glutamicum (5.20 +/- 0.20 kV/cm), and Mycobacterium smegmatis (5.56 +/- 0.08 kV/cm) have been successfully characterized. Determining the critical electric field for electroporation facilitates the development of electroporation protocols that minimize Joule heating and maximize cell viability. This assay will ultimately enable the genetic transformation of bacteria and archaea considered intractable and difficult-to-transfect, while facilitating fundamental genetic studies on numerous diverse microbes. PMID- 26893026 TI - Antiretroviral Preexposure Prophylaxis: Opportunities and Challenges for Primary Care Physicians. PMID- 26893029 TI - Assessment of corneal biomechanical parameters in myopes and emmetropes using the Corvis ST. AB - BACKGROUND: Prior studies have demonstrated conflicting results regarding the relationship between corneal biomechanical properties and refractive error. Thus, the purpose of this study was to compare the corneal biomechanical parameters of myopes and emmetropes. METHODS: Ninety-four subjects with varying degrees of myopia (aged 29 to 74 years, spherical equivalent [SE] -0.5 to -17.5 D) and 25 emmetropes (aged 19 to 75 years, SE: -0.5 to +0.5 D) presenting at the Queen Mary Hospital, Hong Kong were recruited sequentially for this prospective study. All patients were phakic with no history of coexisting ocular disease. The corneal biomechanical parameters of the right eye of each subject were analysed using the Corvis ST non-contact tonometer. Intraocular pressure (IOP) was measured using both the Corvis ST and the Topcon Non-Contact Tonometer CT-80. Refractive error was measured by non-cycloplegic subjective and objective refractometry. RESULTS: High myopes (SE greater than -6.00 D) demonstrated greater mean outward applanation velocities (p < 0.001) and peak distance measurements (p = 0.009) compared to both low to moderate myopes (SE -0.50 to -6.00 D) and emmetropes. Both outward applanation velocity and peak distance were moderately correlated with refractive error (p <= 0.001), strongly correlated with IOP and weakly correlated with central corneal thickness. There were no statistically significant differences in age, IOP or central corneal thickness among emmetropes, low to moderate myopes or high myopes. CONCLUSION: Within this study of Chinese subjects, high myopes demonstrate greater corneal mean outward applanation velocity on Corvis ST testing, than emmetropes. In particular, those with high myopia (SE greater than -6.00 D) show a distinct corneal biomechanical profile relative to those with either emmetropia or low to moderate myopia using the Corvis ST. PMID- 26893028 TI - miR-92b regulates glioma cells proliferation, migration, invasion, and apoptosis via PTEN/Akt signaling pathway. AB - Glioblastoma (GBM) is a highly invasive malignant primary brain tumor with neoplastic growth. Despite the progresses made in surgery, chemotherapy, and radiation in recent decade, the prognosis of patients with gliomas remains poor and the average survival time of patients suffering from glioblastoma is still short. As a potential therapy strategy, microRNAs have been considered as new targets for possible cancer treatment. In this study, we found that the miR-92b inhibitors (miR-92b-I) could inhibit the proliferation, migration, invasion, and promote the apoptosis of glioma cells. As a predicted target of miR-92b, phosphatase and tensin homolog (PTEN), also elevated at both mRNA and protein levels. Moreover, the Akt phosphorylation was consistently inhibited. The rescue experiment with miR-92b and PTEN double knockdown resulted in partial reversion of miR-92b-I-induced phenotypes. Taken together, our findings indicated that miR 92b-I could restrain the proliferation, invasion, migration, and stimulate apoptosis of glioma cells by targeting PTEN/Akt signaling pathway. Further investigations will focus on antitumor effect of miR-92b-I in glioma treatment. PMID- 26893027 TI - A Novel Systems-Biology Algorithm for the Analysis of Coordinated Protein Responses Using Quantitative Proteomics. AB - The coordinated behavior of proteins is central to systems biology. However, the underlying mechanisms are poorly known and methods to analyze coordination by conventional quantitative proteomics are still lacking. We present the Systems Biology Triangle (SBT), a new algorithm that allows the study of protein coordination by pairwise quantitative proteomics. The Systems Biology Triangle detected statistically significant coordination in diverse biological models of very different nature and subjected to different kinds of perturbations. The Systems Biology Triangle also revealed with unprecedented molecular detail an array of coordinated, early protein responses in vascular smooth muscle cells treated at different times with angiotensin-II. These responses included activation of protein synthesis, folding, turnover, and muscle contraction - consistent with a differentiated phenotype-as well as the induction of migration and the repression of cell proliferation and secretion. Remarkably, the majority of the altered functional categories were protein complexes, interaction networks, or metabolic pathways. These changes could not be detected by other algorithms widely used by the proteomics community, and the vast majority of proteins involved have not been described before to be regulated by AngII. The unique capabilities of The Systems Biology Triangle to detect functional protein alterations produced by the coordinated action of proteins in pairwise quantitative proteomics experiments make this algorithm an attractive choice for the biological interpretation of results on a routine basis. PMID- 26893031 TI - Rapid cooling after acute hyperthermia alters intestinal morphology and increases the systemic inflammatory response in pigs. AB - The study objective was to determine the direct effects of rapid cooling after acute hyperthermia on intestinal morphology and inflammatory response in pigs. In four repetitions, male pigs (N = 36; 88.7 +/- 1.6 kg) were exposed to thermoneutrality (TN; n = 3/rep; 19.5 +/- 0.1 degrees C) for 6 h or heat stress (HS; 36.4 +/- 0.1 degrees C) for 3 h, followed by a 3-h recovery period of rapid cooling (HSRC; n = 3/rep; rapid TN exposure and ice water dousing for 1.5 h) or gradual cooling (HSGC; n = 3/rep; gradual decrease from HS to TN). Rectal (TR) and gastrointestinal tract (TGI) temperatures were obtained every 15 min for 6 h. In repetitions 1 and 2, blood was collected at 60 and 180 min during HS and 30 and 60 min during recovery, and then pigs were euthanized at 180 min of recovery and duodenum, ileum, and colon tissue were collected to evaluate intestinal morphology. HS increased (P < 0.01) maximum TR (40.7 degrees C) and TGI (41.5 degrees C) compared with TN treatment (38.9 and 39.3 degrees C, respectively). Recovery reduced TR (P < 0.01; 0.4 degrees C) in HSRC vs. HSGC pigs, but TGI was similar (40.7 degrees C). HSRC reduced (P < 0.01) villus height-to-crypt depth ratio in the duodenum (34%) and ileum (46%) vs. HSGC pigs. Serum LPS concentration was greater in HSRC pigs (P = 0.04; 68.5% and 52.4%, respectively) compared with TN and HSGC pigs, and TNF-alpha concentration tended to be greater (P = 0.06; 41.2%) compared with HSGC pigs during recovery. In summary, rapid cooling reduced TR but had no effect on TGI, and this may be linked to increased intestinal damage and a systemic inflammatory response. PMID- 26893032 TI - A low-cost system to easily measure spontaneous physical activity in rodents. AB - Spontaneous physical activity (SPA) can be responsible for variations of a lot of physiological parameters at the molecular, cellular, tissue, and systemic levels. It is increasingly recognized that good understanding of a large part of experimental results requires weighting them by SPA in order to reduce variability and thus to decrease the number of animals necessary to conduct a study. However, because of the high cost of this equipment, only a few laboratories are equipped with such equipment to measure the SPA of their animals. Here we present an effective, adaptable, and affordable system to measure SPA in rodents based on video acquisition of the animal in its own environment. We compared results obtained with our system to those collected at the same time with a commercial system of actimetry recording, and we found a high degree of correlation between these two approaches (r = 0.93; P < 0.001). We also were able to detect small variations of SPA induced by a special environment like chronic hypoxia exposure (25% less spontaneous activity compared with animals in normoxia, P < 0.05) or during the circadian cycle (107% more activity during the nocturnal phase compared with the diurnal phase, P < 0.05). PMID- 26893030 TI - WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-day bed rest in women. AB - Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6 degrees head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means +/- SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 +/- 3.4%) than in exercisers (4.3 +/- 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 +/- 4.5%), compared with controls (-16.6 +/- 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel. PMID- 26893033 TI - Long-duration bed rest as an analog to microgravity. AB - Long-duration bed rest is widely employed to simulate the effects of microgravity on various physiological systems, especially for studies of bone, muscle, and the cardiovascular system. This microgravity analog is also extensively used to develop and test countermeasures to microgravity-altered adaptations to Earth gravity. Initial investigations of bone loss used horizontal bed rest with the view that this model represented the closest approximation to inactivity and minimization of hydrostatic effects, but all Earth-based analogs must contend with the constant force of gravity by adjustment of the G vector. Later concerns about the lack of similarity between headward fluid shifts in space and those with horizontal bed rest encouraged the use of 6 degree head-down tilt (HDT) bed rest as pioneered by Russian investigators. Headward fluid shifts in space may redistribute bone from the legs to the head. At present, HDT bed rest with normal volunteers is the most common analog for microgravity simulation and to test countermeasures for bone loss, muscle and cardiac atrophy, orthostatic intolerance, and reduced muscle strength/exercise capacity. Also, current physiologic countermeasures are focused on long-duration missions such as Mars, so in this review we emphasize HDT bed rest studies with durations of 30 days and longer. However, recent results suggest that the HDT bed rest analog is less representative as an analog for other important physiological problems of long duration space flight such as fluid shifts, spinal dysfunction and radiation hazards. PMID- 26893035 TI - Elevated gold ellipse nanoantenna dimers as sensitive and tunable surface enhanced Raman spectroscopy substrates. AB - We demonstrate large area arrays of elevated gold ellipse dimers with precisely controlled gaps for use as sensitive and highly controllable surface enhanced Raman scattering (SERS) substrates. The enhanced Raman signal observed with SERS arises from both localized and long range plasmonic effects. By controlling the geometry of a SERS substrate, in this case the size and aspect ratio of individual ellipses, the plasmon resonance can be tuned in a broad wavelength range, providing a method for designing the response of SERS substrates at different excitation wavelengths. Plasmon effects exhibited by the elevated gold ellipse dimer substrates are also demonstrated and confirmed through finite difference time domain (FDTD) simulations. A plasmon resonance red shift with an increase of the ellipse aspect ratio is observed, allowing systematic control of the resulting SERS signal intensity. Optimized elevated ellipse dimer substrates with 10 +/- 2 nm gaps exhibit uniform SERS enhancement factors on the order of 10(9) for adsorbed p-mercaptoaniline molecules. PMID- 26893034 TI - Lung diffusing capacity for nitric oxide as a marker of fibrotic changes in idiopathic interstitial pneumonias. AB - Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO. PMID- 26893036 TI - Synthesis of borocarbonitride from a multifunctional Cu(I) boron imidazolate framework. AB - A functional Cu(I) boron imidazolate framework (BIF) with a ladder-chain structure can not only change to another single-chain structure by incorporating 4,4'-bipyridine, but can also act as a reducing agent to load trimetal Au-Ag-Pd nanoparticles directly; the BIF with loaded noble NPs showed an excellent reduction effect on 4-nitrophenol. Moreover, we obtained a porous borocarbonitride by the direct carbonisation of this low-dimensional BIF. The resulting porous borocarbonitride exhibits fast adsorption behavior for 4 nitrophenol and can be a high-temperature conductor. PMID- 26893037 TI - Molecular identification of potential denitrifying bacteria and use of D-optimal mixture experimental design for the optimization of denitrification process. AB - Three bacterial strains (TE1, TD3 and FB2) were isolated from date palm (degla), pistachio and barley. The presence of nitrate reductase (narG) and nitrite reductase (nirS and nirK) genes in the selected strains was detected by PCR technique. Molecular identification based on 16S rDNA sequencing method was applied to identify positive strains. In addition, the D-optimal mixture experimental design was used to optimize the optimal formulation of probiotic bacteria for denitrification process. Strains harboring denitrification genes were identified as: TE1, Agrococcus sp LN828197; TD3, Cronobacter sakazakii LN828198 and FB2, Pedicoccus pentosaceus LN828199. PCR results revealed that all strains carried the nirS gene. However only C. sakazakii LN828198 and Agrococcus sp LN828197 harbored the nirK and the narG genes respectively. Moreover, the studied bacteria were able to form biofilm on abiotic surfaces with different degree. Process optimization showed that the most significant reduction of nitrate was 100% with 14.98% of COD consumption and 5.57 mg/l nitrite accumulation. Meanwhile, the response values were optimized and showed that the most optimal combination was 78.79% of C. sakazakii LN828198 (curve value), 21.21% of P. pentosaceus LN828199 (curve value) and absence (0%) of Agrococcus sp LN828197 (curve value). PMID- 26893038 TI - Reconstructive Endovascular Treatment of an Intracranial Infectious Aneurysm in Bacterial Meningitis: A Case Report and Review of Literature. AB - BACKGROUND: Intracranial infectious aneurysms (IAs) are rare cerebrovascular lesions that represent only 1%-6% of all intracranial aneurysms. IAs are rare cerebrovascular lesions and pose a significant therapeutic challenge because of their angiographic and pathophysiologic features. We describe a patient with an intracranial IA treated by the use of reconstructive endovascular methods using a balloon-expandable covered stent and discuss the pathophysiologic characteristics of IA based on serial brain imaging findings. CASE DESCRIPTION: A 21-year-old man was admitted to our emergency department with headache and vomiting. Neurologic examination, hematologic workup, and cerebrospinal fluid examination confirmed a diagnosis of bacterial meningitis. Initial brain magnetic resonance angiography revealed no significant stenosis lesions or aneurysm. After 4 weeks of antibiotic treatment, follow-up brain magnetic resonance imaging revealed an 8-mm sized aneurysm on the petrous portion of the right internal carotid artery, and 3 months later, follow-up brain magnetic resonance angiography revealed that the aneurysm had increased in size from 8 to 15 mm. Conventional 4-vessel angiography confirmed the presence of a pseudoaneurysm. Endovascular treatment was then planned via the use of a balloon-expandable covered stent. Postoperatively, the patient was discharged without specific neurologic deficit. CONCLUSIONS: IAs are rare cerebrovascular lesions and pose a significant therapeutic challenge because of their angiographic and pathophysiologic features. Although endovascular treatment is not performed routinely for infectious aneurysms, the covered stent may represent a safe and effective treatment that achieves complete endoluminal reconstruction of the damaged vessel wall. PMID- 26893039 TI - Should Cervical Disc Arthroplasty Be Done on Patients with Increased Intramedullary Signal Intensity on Magnetic Resonance Imaging? AB - OBJECTIVE: Several trials from the U.S. Food and Drug Administration have demonstrated the success of cervical disc arthroplasty (CDA) in patients with degenerative disc disease causing radiculopathy, myelopathy, or both. For patients who had increased intramedullary signal intensity (IISI) on magnetic resonance image (MRI), however, the effectiveness and safety of CDA was unclear. This study aimed to evaluate the outcomes of CDA for patients with IISI on preoperative MRI. METHODS: Consecutive patients who received 1-level CDA for symptomatic degenerative disc disease were reviewed retrospectively. Patients with IISI on preoperative T2-weighted MRI were compared to those without IISI (non-IISI). Clinical outcome parameters including visual analog scale, Neck Disability Index, Japanese Orthopedic Association (JOA), and Nurick scores were analyzed. Radiographic studies included dynamic lateral radiography and MRI. RESULTS: A total of 91 patients were analyzed (22 in the IISI group and 69 in the non-IISI group). The mean follow-up was 30.0 months. The demographic data were mostly similar between the 2 groups. All clinical outcomes, including visual analog scale, Neck Disability Index, JOA, and Nurick scores in the IISI group demonstrated significant improvement after operation. The IISI group had similar clinical outcomes to the non-IISI group, except that the JOA scores were generally worse. Follow-up MRI demonstrated significant regression of the length of IISI (P = 0.009). Both groups had preserved motion after CDA. CONCLUSIONS: Both clinical and radiological outcomes improved (the average length of IISI in the cervical spinal cord became shorter) after CDA. Therefore, CDA is a safe and effective option for patients even when there is IISI on the preoperative T2 weighted MRI. PMID- 26893040 TI - Delayed Occipital Artery Pseudoaneurysm Following Blunt Force Trauma. AB - BACKGROUND: Occipital artery pseudoaneurysms are extremely rare pathologies that manifest after traumatic injury; only 11 cases have been reported in the literature. Because of their low incidence and vague symptoms, the initial diagnosis can be difficult. However, for correctly diagnosed occipital artery pseudoaneurysms, many successful treatment modalities exist. METHODS: We review the pathology of occipital pseudoaneurysms, elucidate the reasons for their rarity, discuss effective diagnostic measures, and discuss the currently available treatment options. We also present a case of a 16-year-old boy who sustained blunt force trauma in May 2014 and presented 6 months later with a painful, pulsatile mass in the occipital region. RESULTS: The patient underwent surgical resection to alleviate the pain and the potential risk of hemorrhage. He experienced complete resolution of pain and associated symptoms. CONCLUSIONS: Our case highlights the fact that occipital swelling, a significant initial sign of pseudoaneurysm development, can be delayed. Therefore, occipital artery pseudoaneurysms cannot be ruled out of the differential diagnosis based on time course alone. Surgical resection is a quick and effective method for relief of severe pain resulting from occipital artery pseudoaneurysms. Although they are rare entities, occipital artery pseudoaneurysms must be considered in the differential diagnosis of cases of pulsatile mass lesions in the posterior scalp. PMID- 26893041 TI - CT/MRI Fusion for Vascular Mapping and Navigated Resection of a Paraspinal Tumor. AB - BACKGROUND: Computed tomography/magnetic resonance imaging (CT/MRI) fusion is used increasingly in the surgical treatment of cranial pathology. The merging of these complementary modalities provides excellent visualization of the bony anatomy and clear delineation of the soft tissues, including neurovascular structures. To our knowledge, the application of CT/MRI fusion for the surgical management of spinal pathology has not been reported previously. CASE DESCRIPTION: A 70-year-old woman presented with a paraspinal tumor that originated from the right psoas muscle and extended into the lumbar neuroforamina, with intricate involvement of the lumbar plexus and retroperitoneal vasculature. CT/MRI fusion was used to map out the vessels surrounding the tumor and for intraoperative navigation during resection of this invasive paraspinal tumor. CONCLUSIONS: This case highlights both the feasibility and the advantages of applying CT/MRI fusion technology to the surgical treatment of spinal pathology. PMID- 26893042 TI - Outcomes of Subdural Grid Electrode Monitoring in the Stereoelectroencephalography Era. AB - BACKGROUND: Subdural grid (SDG) electrodes have been the gold standard of invasive monitoring in medically refractory epilepsy; however, in some centers, application of SDGs has been reduced by the progressive application of stereoelectroencephalography (SEEG). This study reviews the efficacy of SDG electrode monitoring after the incorporation of the SEEG methodology at our institution. METHODS: We retrospectively reviewed 102 patients undergoing intracranial monitoring via SDG electrodes during the years 2010-2013 at our institution. The series includes all patients who underwent SDG placement after the incorporation of SEEG in our extraoperative invasive monitoring armamentarium. RESULTS: Average patient age was 29.9 years old; the series included 31 pediatric patients. There were 49 male patients and 53 female patients. The mean length of follow-up was 21.5 months. The epileptogenic zone was localized in 99 (97%) patients. Surgical resection was performed in 84 patients, and 70% experienced Engel class I freedom from seizures. CONCLUSIONS: Invasive monitoring via SDG electrodes continues to be an efficacious option for select patients with medically refractory epilepsy, mainly when the hypothetical epileptogenic zone is anatomically restricted to superficial cortical areas and in close relation with eloquent cortex. This is the first report of epilepsy outcomes after SDG monitoring at a center that also performs SEEG monitoring. Our results suggest a complementary benefit of performing both techniques at 1 institution. PMID- 26893045 TI - Mechanical, structural and thermal properties of Ag-Cu and ZnO reinforced polylactide nanocomposite films. AB - Plasticized polylactic acid (PLA) based nanocomposite films were prepared by incorporating polyethylene glycol (PEG) and two selected nanoparticles (NPs) [silver-copper (Ag-Cu) alloy (<100 nm) and zinc oxide (ZnO) (<50 and <100 nm)] through solvent casting method. Incorporation of Ag-Cu alloy into the PLA/PEG matrix increased the glass transition temperature (Tg) significantly. The crystallinity of the nanocomposites (NCs) was significantly influenced by NP incorporation as evidenced from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The PLA nanocomposite reinforced with NPs exhibited much higher tensile strength than that of PLA/PEG blend. Melt rheology of NCs exhibited a shear-thinning behavior. The mechanical property drastically reduced with a loading of NPs, which is associated with degradation of PLA. SEM micrographs exhibited that both Ag-Cu alloy and ZnO NPs were dispersed well in the PLA film matrix. PMID- 26893044 TI - Trochlear Nerve Neurofibroma in a Clinically NF-1-Negative Patient; A Case Report and Review of Literature. AB - BACKGROUND: Isolated orbital neurofibroma unassociated with systemic neurofibromatosis is relatively rare and may be difficult to clinically differentiate from other orbital tumors. Sensory branches of the trigeminal nerve namely lacrimal, nasociliary, and frontal-are the most common nerves of origin for intraorbital neurofibroma, but we discovered a neurofibroma arising out of the right trochlear nerve, in absence of clinical stigmata of neurofibromatosis type 1, which is rare. CASE DESCRIPTION: A 41-year-old adult presented with painless progressive proptosis of the right eye for 10 years without history of visual problems or diplopia. The right eye had axial proptosis with periorbital swelling. On magnetic resonance imaging (MRI), a right orbital extraconal, expansile, lobulated, cystic space-occupying lesion was seen with an enhancing component, pushing the lateral rectus with T1 isointensity and T2 hyperintensity, suggesting a preoperative working diagnosis of pseudotumor or lymphoproliferative tumor. Intraoperatively, a rudimentary slender, white, elongated structure was passing through the length of the tumor. The elongated tumor engulfing the trochlear nerve was traced up to the lateral part of the superior orbital fissure. The tumor was excised completely and was found to be a neurofibroma. CONCLUSION: Isolated trochlear nerve neurofibromas, in the absence of clinical stigmata of NF1, are rare. Multiplicity, multilobulation, ring-configured contrast enhancement, and heterogenous MRI signal intensities help in the accurate preoperative imaging diagnosis. A possible cure is thus achievable with complete excision without damaging important adjacent neurovasculo musculotendinous structures in the orbit. To the best of our knowledge, this is the fourth reported case of isolated trochlear nerve neurofibroma. PMID- 26893043 TI - (18)F-Fluoroethyl-l-Thyrosine Positron Emission Tomography to Delineate Tumor Residuals After Glioblastoma Resection: A Comparison with Standard Postoperative Magnetic Resonance Imaging. AB - OBJECTIVE: Complete resection of contrast-enhancing tumor is an important prognostic factor in glioblastoma therapy. The current clinical standard for control of resection is magnetic resonance imaging (MRI). (18)F-Fluoroethyl-l thyrosine (FET) is a positron emission tomography (PET) radiopharmaceutical applicable for widespread use because of its long half-life radionuclide. We assessed the sensitivity of postoperative MRI versus FET-PET to detect residual tumor and the impact of the time interval between resection and FET-PET. METHODS: MRI and FET-PET were performed preoperatively and postoperatively in 62 patients undergoing 63 operations. FET-PET was performed in 43 cases within 72 hours after resection and in 20 cases >72 hours after resection. Detection and measurement of volume of residual tumors were compared. Correlations between residual tumor detection and timing of PET after resection and recurrence were examined. RESULTS: Complete resection was confirmed by both imaging modalities in 44% of cases, and residual tumor was detected consistently in 37% of cases. FET-PET detected residual tumor in 14% of cases in which MRI showed no residual tumor. MRI showed residual tumors in 5% of cases that were not identified by PET. Average PET-based residual tumor volume was higher than MRI-based volume (3.99 cm(3) vs. 1.59 cm(3)). Detection of and difference in volume of residual tumor were not correlated with timing of PET after resection or recurrence status. CONCLUSIONS: Postoperative FET-PET revealed residual tumor with higher sensitivity than MRI and showed larger tumor volumes. In this series, performing PET >72 hours after resection did not influence the results of PET. We recommend FET-PET as a helpful adjunct in addition to MRI for postoperative assessment of residual tumor. PMID- 26893046 TI - Thermal stability enhancement of modified carboxymethyl cellulose films using SnO2 nanoparticles. AB - In this study, in-situ and ex-situ hydrothermal synthesis procedures were applied to synthesize novel CMC/porous SnO2 nanocomposites from rice husk extracted carboxymethyl cellulose (CMC) biopolymer. In addition, the effects of SnO2 nanoparticles on thermal stability of the prepared nanocomposite were specifically studied. Products were investigated in terms of morphology, particle size, chemical structure, crystallinity and thermal stability by using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA), respectively. Presence of characteristic bands in the FTIR spectra of samples confirmed the successful formation of CMC and CMC/SnO2 nanocomposites. In addition, FESEM images revealed four different morphologies of porous SnO2 nanoparticles including nanospheres, microcubes, nanoflowers and olive-like nanoparticles with hollow cores which were formed on CMC. These nanoparticles possessed d-spacing values of 3.35A. Thermal stability measurements revealed that introduction of SnO2 nanoparticles in the structure of CMC enhanced stability of CMC to 85%. PMID- 26893048 TI - Sulfated modification of the polysaccharide from Sphallerocarpus gracilis and its antioxidant activities. AB - Sphallerocarpus gracilis (S. gracilis) is a little-investigated edible plant and used as traditional Chinese medicine. In this study, polysaccharide extracted from S. gracilis,deproteined and purified. The polysaccharide (SGP) was chemically modified to obtain its sulfated derivatives (S-SGP) using the method of chlorosulfonic acid/pyridine (CSA/Pyr). In order to acquire the derivative with the highest degree of substitution (DS), the optimum conditions of the sulfation were obtained based on response surface design (RSD), and the structural characterizations and antioxidant properties of the S-SGP were comparatively investigated by Fourier transform infrared spectrometry (FT-IR), GC MS analysis, size exclusion chromatography (SEC), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay, and reducing power assay, respectively. Results showed that the modification was successful, and obtained the optimum combination of conditions. Compared with SGP, the sulfated polysaccharide with relatively the decreased degree of molecular weight (Mw) but the same composition of monosaccharides exhibited better antioxidant activities in DPPH, hydroxyl, superoxide radical and reducing power assay. These results indicated that the antioxidant activities in vitro of the S-SGP from S. gracilis may be related to combined effects of Mw, monosaccharide composition, and sulfate content. PMID- 26893049 TI - Effect of drying and loading methods on the release behavior of ciprofloxacin from starch nanoparticles. AB - Drug loading into and release from starch nanoparticles (StNPs), one kind of novel biological macromolecule, were investigated. Two drying methods (spray and vacuum freeze drying) and drug loading methods (coating and adsorption) were used for evaluation. 40% (w/w) of ciprofloxacin was loaded using coating method while only 7% for adsorption method. Glass transition temperature (Tg) and melting point temperature (Tmp) of ciprofloxacin loaded starch nanoparticles varied from 40 degrees C to 55 degrees C and 125 degrees C to 175 degrees C. Particles using adsorption method had lower loading rate of ciprofloxacin, higher Tg, Tmp and release rate compared to using coating method. Tg and Tmp were not affected by these two drying methods. Release rate of ciprofloxacin was higher from freeze dried particles than from spray dried particles using coating method. For adsorption method, drying methods had not effect on the release rate. A double decay exponential model was able to fit the release data suitably well with coefficient of determination (R(2))>0.97. PMID- 26893047 TI - Tailoring the degradation rate and release kinetics from poly(galactitol sebacate) by blending with chitosan, alginate or ethyl cellulose. AB - Despite significant advances in recent times, the investigation of discovering a perfect biomaterial is perennial. In this backdrop, blending of natural and synthetic polymers is gaining popularity since it is the easiest way to complement the drawbacks and attain a superlative material. Based on this, the objective of this study was to synthesize a novel polyester, poly(galactitol sebacate), and subsequently blend this polymer with one of the three natural polymers such as alginate, chitosan or ethyl cellulose. FT-IR showed the presence of both the polymers in the blends. 1H NMR confirmed the chemical structure of the synthesized poly (galactitol sebacate). Thermal characterization was performed by DSC revealing that the polymers were amorphous in nature and the glass transition temperatures increased with the increase in ratio of the natural polymers in the blends. SEM imaging showed that the blends were predominantly homogeneous. Contact angle measurements demonstrated that the blending imparted the hydrophilic nature into poly (galactitol sebacate) when blending with alginate or chitosan and hydrophobic when blending with ethyl cellulose. In vitro hydrolytic degradation studies and dye release studies indicated that the polymers became more hydrophilic in alginate and chitosan blends and thus accelerated the degradation and release process. The reverse trend was observed in the case of ethyl cellulose blends. Modeling elucidated that the degradation and dye release followed first order kinetics and Higuchi kinetics, respectively. In vitro cell studies confirmed the cytocompatible nature of the blends. It can be proposed that the chosen natural polymers for blending showed wide variations in hydrophilicity resulting in tailored degradation, release and cytocompatibility properties and thus are promising candidates for use in drug delivery and tissue engineering. PMID- 26893050 TI - Biomaterials based on N,N,N-trimethyl chitosan fibers in wound dressing applications. AB - In the present work, N,N,N-trimethyl chitosan (TMC) fibers were synthesized successfully and the resulting quaternized materials were characterized by FTIR. The designed TMC fibers with different degree of quaternization achieved high water absorption capability. In antibacterial activity study, TMC fibers showed high antibacterial activity than chitosan fibers against the gram-negative bacteria Escherichia coli (>63%) and gram-positive bacteria Staphylococcus aureus (>99%). TMC fibers exhibited no obvious cytotoxicity to mouse embryo fibroblast cells with low extraction concentrations (<0.05g/mL). In animal wound healing test, TMC2 fibers could significantly enhance wound re-epithelialization and contraction compared with the control (chitosan fibers). In conclusion, TMC fibers have a potential to be used as wound dressing materials. PMID- 26893051 TI - Chitosan functionalized poly(vinyl alcohol) for prospects biomedical and industrial applications: A review. AB - Chitin and chitosan are amino polysaccharides having multidimensional properties, such as biocompatibility, biodegradability, antibacterial properties and non toxicity, muco-adhesivity, adsorption properties, etc., and thus they can be widely used in variety of areas. Although human history mainly relies on the biopolymers, however synthetic materials like polyvinyl alcohol (PVA) have good mechanical, chemical and physical properties. Functionalization of PVA with chitin and chitosan is considered very appropriate for the development of well designed biomaterials such as biodegradable films, for membrane separation, for tissue engineering, for food packaging, for wound healing and dressing, hydro gels formation, gels formation, etc. Considering versatile properties of the chitin and chitosan, and wide industrial and biomedical applications of PVA, this review sheds a light on chitin and chitosan based PVA materials with their potential applications especially focusing the bio-medical field. All the technical scientific issues have been addressed highlighting the recent advancement. PMID- 26893052 TI - Optimizing indomethacin-loaded chitosan nanoparticle size, encapsulation, and release using Box-Behnken experimental design. AB - Indomethacin chitosan nanoparticles (NPs) were developed by ionotropic gelation and optimized by concentrations of chitosan and tripolyphosphate (TPP) and stirring time by 3-factor 3-level Box-Behnken experimental design. Optimal concentration of chitosan (A) and TPP (B) were found 0.6mg/mL and 0.4mg/mL with 120min stirring time (C), with applied constraints of minimizing particle size (R1) and maximizing encapsulation efficiency (R2) and drug release (R3). Based on obtained 3D response surface plots, factors A, B and C were found to give synergistic effect on R1, while factor A has a negative impact on R2 and R3. Interaction of AB was negative on R1 and R2 but positive on R3. The factor AC was having synergistic effect on R1 and on R3, while the same combination had a negative effect on R2. The interaction BC was positive on the all responses. NPs were found in the size range of 321-675nm with zeta potentials (+25 to +32mV) after 6 months storage. Encapsulation, drug release, and content were in the range of 56-79%, 48-73% and 98-99%, respectively. In vitro drug release data were fitted in different kinetic models and pattern of drug release followed Higuchi matrix type. PMID- 26893053 TI - Emerging roles of hyaluronic acid bioscaffolds in tissue engineering and regenerative medicine. AB - Hyaluronic acid (HA), is a glycosaminoglycan comprised of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid. HA is synthesized by hyaluronan synthases and reaches sizes in excess of 2MDa. It plays numerous roles in normal tissues but also has been implicated in inflammatory processes, multiple drug resistance, angiogenesis, tumorigenesis, water homeostasis, and altered viscoelasticity of extracellular matrix. The physicochemical properties of HA including its solubility and the availability of reactive functional groups facilitate chemical modifications on HA, which makes it a biocompatible material for use in tissue regeneration. HA-based biomaterials and bioscaffolds do not trigger allergies or inflammation and are hydrophilic which make them popular as injectable dermal and soft tissue fillers. They are manufactured in different forms including hydrogels, tubes, sheets and meshes. Here, we review the pathophysiological and pharmacological properties and the clinical uses of native and modified HA. The review highlights the therapeutic applications of HA-based bioscaffolds in organ-specific tissue engineering and regenerative medicine. PMID- 26893054 TI - Preparation and characterization of acetylated starch nanoparticles as drug carrier: Ciprofloxacin as a model. AB - The objective of this study was to characterize in-vitro the potential of acetylated corn starch (ACS) particles as a matrix for the delivery of ciprofloxacin (CFx). ACS was successfully synthesized and optimized by the reaction of native corn starch using acetic anhydride and acetic acid with low and high degrees of substitution (DS). The nanoprecipitation method was applied for the formation of the ACS-based nanoparticles, by the dropwise addition of water to acetone solution of ACS under stirring. The effects of acetylation and nanoprecipitation on the morphology and granular structure of ACS samples were examined by the FT-IR, XRD, DSL and SEM techniques. The efficiency of CFx loading was also evaluated via encapsulation efficiency (EE) in ACS nanoparticles. The average degree of acetyl substitution per glucose residue of corn starch was 0.33, 2.00, and 2.66. The nanoparticles size of the ACS and ACS-loaded with CFx were measured and analyzed relative to the solvent:non-solvent ratio. Based on the results, ACS nanoparticles with DS of 2.00 and water:acetone of 3:1 had 312nm diameter. Increasing DS in starch acetate led to increase in the EE from 67.7 to 89.1% and with increasing ratio of water/acetone from 1:1 to 3:1, the EE raised from 48.5 to 89.1%. X-ray diffraction indicated that A-type pattern of native starch was completely transformed into the V-type pattern of acetylated starch. The scanning electron microscopy showed that the different sizes of pores formed on the acetylated starch granules were utterly converted into the uniform-sized spherical nanoparticles after the nanoprecipitation. PMID- 26893055 TI - Polysaccharide from Angelica sinensis protects chondrocytes from H2O2-induced apoptosis through its antioxidant effects in vitro. AB - This study aimed to explore the protective effects of Angelica sinensis polysaccharide (ASP) on rat chondrocyte injury induced by hydrogen peroxide (H2O2). Rat chondrocytes were cultured and treated with different concentrations of ASP alone or in combination with H2O2, and they were measured with cell viability, apoptosis, release of inflammatory cytokines, such as interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), activity of superoxide dismutase (SOD), and catalase (CAT), and levels of malondialdehyde (MDA) production, respectively. In addition, quantitative real-time reverse transcription polymerase chain reaction was used to estimate the relative expression levels of osteoarthritis (OA)-associated genes, such as collagen type II (Col2a1), aggrecan, SOX9, matrix metalloproteinase (MMP)-1, -3, and -9, as well as tissue inhibitor of matrix metalloproteinase (TIMP)-1, respectively. Results indicated that ASP protected chondrocytes from H2O2-induced oxidative stress and subsequent cell injury through its antioxidant, antiapoptotic and anti inflammatory effects in vitro. Our study suggests that ASP could become a therapeutic supplementation for the treatment of OA. PMID- 26893056 TI - Vanillin restrains non-enzymatic glycation and aggregation of albumin by chemical chaperone like function. AB - Vanillin a major component of vanilla bean extract is commonly used a natural flavoring agent. Glycation is known to induce aggregation and fibrillation of globular proteins such as albumin, hemoglobin. Here we report the inhibitory potential of vanillin toward early and advanced glycation modification and amyloid like aggregation of albumin based on the determination of both early and advanced glycation and conformational changes in albumin using circular dichroism. Inhibition of aggregation and fibrillation of albumin was determined based on amyloid specific dyes i.e., Congo red and Thioflavin T and microscopic imaging. It was evident that vanillin restrains glycation of albumin and exhibits protective effect toward its native conformation. PMID- 26893057 TI - Gas-Phase Reactions of Glyceraldehyde and 1,3-Dihydroxyacetone as Models for Levoglucosan Conversion during Biomass Gasification. AB - Levoglucosan, the major intermediate in wood gasification, is decomposed selectively to C1/C2 fragments at 550-600 degrees C. Kinetic analyses suggest that radical chain mechanisms with the involvement of short-lived carbonyl intermediates explain the lower production of larger fragments. To address this hypothesis, the gas-phase reactivities of glyceraldehyde (Gald), 1,3 dihydroxyacetone (DHA), and glycerol, as simple C3 model compounds, were compared at 400-800 degrees C under N2 flow at residence times of 0.9-1.4 s. Retro-aldol fragmentation and dehydration proceeded for the pyrolysis of Gald/DHA at 400 degrees C, far below the 600 degrees C decomposition point of glycerol. Pyrolysis of Gald/DHA generated exclusively syngas (CO and H2). On the basis of the results of theoretical calculations, the effects of carbonyl intermediates on reactivity were explained by postulating uni- and bimolecular reactions, although the bimolecular reactions became less effective at elevated temperatures. PMID- 26893058 TI - Chemosensitization of doxorubicin in multidrug-resistant cells by unimolecular micelles via increased cellular accumulation and apoptosis. AB - OBJECTIVES: Unimolecular micelles were prepared by modification of polyamidoamine (PAMAM) dendrimers using Pluronic F127 (PF127), which is expected to reverse multidrug resistance (MDR). And the reversal mechanisms have been studied. METHODS: Characterization of the products was carried on. MTT assay was used to evaluate the cytotoxicity of the DOX-loaded conjugates. Cellular uptake study was measured by confocal laser scanning microscope and flow cytometry. Apoptosis assay was identified by Annexin V-FITC/PI apoptosis assay and Hoechst 33 342 staining. KEY FINDINGS: Improved cytotoxicity of DOX-loaded conjugates in MCF 7/ADR cells (as much as 33-fold according to the IC50 values) was observed in contrast with that of free DOX. The DOX-loaded conjugates induced a much quicker and 100% uptake in MCF-7/ADR cells, and more than fivefold accumulation of DOX loaded conjugates was observed compared with free DOX. Apoptosis assay showed that DOX-loaded conjugates decreased the cell viability from 81.87 +/- 5.94% to 54.83 +/- 3.63% (DOX concentration 2 MUg/ml). At 48 h, more accumulation and distribution in the nuclei were observed after treatment with DOX-loaded conjugates. CONCLUSIONS: PF127-PAMAM conjugates showed superiority in the treatment of MCF-7/ADR, which implied the potential vehicles of anticancer drugs for the reversal of MDR. PMID- 26893059 TI - Undernourished Children and Milk Lactose. AB - BACKGROUND: Lactose is an important energy source in young mammals, and in fully breast-fed human infants, it constitutes around 40% of the total daily energy intake. The role of lactose in feeding of undernourished infants and young children is not well described. OBJECTIVE: A narrative review of the potential positive and negative effects of lactose in the treatment of undernourished children. METHODS: Searches were conducted using PUBMED and Web of Science up to July 2015. Relevant references in the retrieved articles were included. RESULTS: Lactose may exhibit several health benefits in young children, including a prebiotic effect on the gut microbiota and a positive effect on mineral absorption. Studies in piglets suggest there might also be a stimulating effect on growth, relative to other carbohydrates. Lactose intolerance is a potential concern for undernourished children. Most undernourished children seem to tolerate the currently recommended (low lactose level) therapeutic foods well. However, a subgroup of severely undernourished children with secondary lactase deficiency due to severe diarrhea or severe enteropathy may benefit from products with even more restricted lactose content. At limited extra costs, lactose or lactose-containing milk ingredients may have beneficial effects if added to food products for undernourished children. CONCLUSIONS: Lactose may be an overlooked beneficial nutrient for young and undernourished children. Research is needed to define the balance between beneficial and detrimental effects of lactose in undernourished children at different ages and with different degrees of diarrhea and intestinal integrity. PMID- 26893060 TI - Assessing the Safety of Vitamin A Delivered Through Large-Scale Intervention Programs: Workshop Report on Setting the Research Agenda. AB - BACKGROUND: Vitamin A (VA) deficiency (VAD) is still a concern in many parts of the world, and multiple intervention strategies are being implemented to reduce the prevalence of VAD and associated morbidity and mortality. Because some individuals within a population may be exposed to multiple VA interventions, concerns have been raised about the possible risk of hypervitaminosis A. OBJECTIVES: A consultative meeting was held in Vienna, Austria, in March 2014 to (1) review current knowledge concerning the safety and effectiveness of large scale programs to control VAD, (2) develop a related research agenda, and (3) review current available methods to assess VA status and risk of hypervitaminosis A. METHODS: Multiple countries were represented and shared their experiences using a variety of assessment methods, including retinol isotope dilution (RID) techniques. Discussion included next steps to refine assessment methodology, investigate RID limitations under different conditions, and review programmatic approaches to ensure VA adequacy and avoid excessive intakes. RESULTS: Fortification programs have resulted in adequate VA status in Guatemala, Zambia, and parts of Cameroon. Dietary patterns in several countries revealed that some people may consume excessive preformed VA from fortified foods. CONCLUSION: Additional studies are needed to compare biomarkers of tissue damage to RID methods during hypervitaminosis A and to determine what other biomarkers can be used to assess excessive preformed VA intake. PMID- 26893061 TI - Social Media and the Adolescent and Young Adult (AYA) Patient with Cancer. AB - Over 70,000 adolescent and young adults (AYA) aged 15 to 39 years are diagnosed with cancer each year in the US. The National Cancer Institute (NCI) has identified AYA cancer patients as a unique population. The most common cancers in this age group include tumors typically seen in pediatric patients such as acute lymphoblastic leukemia (ALL) and brain tumors, as well as cancers more typically seen in adult patients such as breast cancer and melanoma. In addition, some cancers have their highest incidence in AYA patients, such as Hodgkin Lymphoma, testicular cancer, and bone tumors. AYA patients face additional unique issues due to their age, not just questions about treatment choices due to lack of data but also questions about fertility, relationships, loss of autonomy, and interruptions in school/work with potentially significant financial complications. This age group also has very high rates of social media usage with up to 90 % of adults aged 18 to 29 using social networking sites. In this review, we will describe the use of social media in AYAs with cancer and highlight some of the online resources for AYAs. PMID- 26893062 TI - Consolidation and Maintenance Therapies for Newly Diagnosed Multiple Myeloma in the Era of Novel Agents. AB - Advances in therapy in multiple myeloma have resulted in significant improvements in patient outcomes; however, relapse remains problematic. Strategies to improve outcomes following autologous stem cell transplantation (ASCT) include consolidation to intensify therapy and improve depth of response and maintenance therapy to achieve long-term disease control. Immunomodulatory drugs (IMiDs), including thalidomide and lenalidomide, are appealing as maintenance therapy given their oral administration; however, the cumulative toxicities of thalidomide have limited its efficacy in maintenance therapy. Maintenance lenalidomide is better tolerated, and multiple studies have demonstrated an improvement in progression-free survival (PFS), but its impact on overall survival (OS) remains controversial. Additional concerns regarding the risk of second primary malignancies and significant cost of long-term lenalidomide therapy have also been raised. Proteasome inhibitors, particularly, bortezomib have also been incorporated in consolidation and maintenance regimens alone or in combination with an IMiD. Preliminary studies have suggested bortezomib maintenance may benefit patients with adverse cytogenetics, including t(4;14) and deletion 17p. Determination of the optimal consolidation and maintenance regimen and duration of therapy post-transplantation is a focus of several ongoing randomized studies. PMID- 26893063 TI - Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents. AB - The field of oncology has been transformed over the course of the last 20 years in large part due to the enhanced understanding of cellular biology and cellular signaling. The indolent natural history of chronic lymphocytic leukemia (CLL) has permitted extensive study of cancer biology and can in some ways be thought of a model for understanding and translating concepts to other diseases. By systematically probing the biology of CLL cells and working out in stepwise fashion the transduction of signals from the surface immunoglobulin to nuclear transcription factors, investigators have paved the way for rational targeting of therapies at natural vulnerabilities that mimic oncogene addiction. These key targets include Bruton's tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K), Src, Bcl2, and cyclin-dependent kinases (CDKs). In this review, we will consider these proteins and describe the current and future molecules designed to target them in CLL. PMID- 26893064 TI - Anatomical and visual outcomes of autologous thrombocyte serum concentrate in the treatment of persistent full-thickness idiopathic macular hole after ILM peeling with brilliant blue G and membrane blue dual. PMID- 26893065 TI - Effects of Physician-directed Pharmaceutical Promotion on Prescription Behaviors: Longitudinal Evidence. AB - Spending on prescription drugs (Rx) represents one of the fastest growing components of US healthcare spending and has coincided with an expansion of pharmaceutical promotional spending. Most (83%) of Rx promotion is directed at physicians in the form of visits by pharmaceutical representatives (known as detailing) and drug samples provided to physicians' offices. Such promotion has come under increased public scrutiny, with critics contending that physician directed promotion may play a role in raising healthcare costs and may unduly affect physicians' prescribing habits towards more expensive, and possibly less cost-effective, drugs. In this study, we bring longitudinal evidence to bear upon the question of how detailing impacts physicians' prescribing behaviors. Specifically, we examine prescriptions and promotion for a particular drug class based on a nationally representative sample of 150,000 physicians spanning 24 months. The use of longitudinal physician-level data allows us to tackle some of the empirical concerns in the extant literature, virtually all of which have relied on aggregate national data. We estimate fixed-effects specifications that bypass stable unobserved physician-specific heterogeneity and address potential targeting bias. In addition, we also assess differential effects at both the extensive and intensive margins of prescribing behaviors and differential effects across physician-level and market-level characteristics, questions that have not been explored in prior work. The estimates suggest that detailing has a significant and positive effect on the number of new scripts written for the detailed drug, with an elasticity magnitude of 0.06. This effect is substantially smaller than those in the literature based on aggregate information, suggesting that most of the observed relationship between physician-directed promotion and drug sales is driven by selection bias. We find that detailing impacts selective brand-specific demand but does not have any substantial effects on class-level demand. The increase in brand-specific demand appears to crowd out demand for the substitute branded drug although not for the generic alternative. Results also indicate that most of the detailing response may operate at the extensive margin; detailing affects the probability of prescribing the drug more than it affects the number of prescriptions conditional on any prescribing. We draw some implications from these estimates with respect to effects on healthcare costs and public health. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26893067 TI - Signalling: Putting the brakes on KRAS-G12C nucleotide cycling. PMID- 26893068 TI - Immunotherapy: Two antigens are better than one. PMID- 26893069 TI - Transmission comb of a distributed Bragg reflector with two surface dielectric gratings. AB - The transmission behaviour of a distributed Bragg reector (DBR) with surface dielectric gratings on top and bottom is studied. The transmission shows a comb like spectrum in the DBR band gap, which is explained in the Fano picture. The number density of the transmission peaks increases with increasing number of cells of the DBR, while the ratio of the average full width at half maximum to the corresponding average free spectral range, being only few percent for both transversal electric and magnetic waves, is almost invariant. The transmission peaks can be narrower than 0.1 nm and are fully separated from each other in certain wavebands. We further prove that the transmission combs are robust against randomness in the heights of the DBR layers. Therefore, the proposed structure is a candidate for an ultra-narrow-band multichannel filter or polarizer. PMID- 26893066 TI - Optimizing mouse models for precision cancer prevention. AB - As cancer has become increasingly prevalent, cancer prevention research has evolved towards placing a greater emphasis on reducing cancer deaths and minimizing the adverse consequences of having cancer. 'Precision cancer prevention' takes into account the collaboration of intrinsic and extrinsic factors in influencing cancer incidence and aggressiveness in the context of the individual, as well as recognizing that such knowledge can improve early detection and enable more accurate discrimination of cancerous lesions. However, mouse models, and particularly genetically engineered mouse (GEM) models, have yet to be fully integrated into prevention research. In this Opinion article, we discuss opportunities and challenges for precision mouse modelling, including the essential criteria of mouse models for prevention research, representative success stories and opportunities for more refined analyses in future studies. PMID- 26893070 TI - Functional dissociation in sweet taste receptor neurons between and within taste organs of Drosophila. AB - Finding food sources is essential for survival. Insects detect nutrients with external taste receptor neurons. Drosophila possesses multiple taste organs that are distributed throughout its body. However, the role of different taste organs in feeding remains poorly understood. By blocking subsets of sweet taste receptor neurons, we show that receptor neurons in the legs are required for immediate sugar choice. Furthermore, we identify two anatomically distinct classes of sweet taste receptor neurons in the leg. The axonal projections of one class terminate in the thoracic ganglia, whereas the other projects directly to the brain. These two classes are functionally distinct: the brain-projecting neurons are involved in feeding initiation, whereas the thoracic ganglia-projecting neurons play a role in sugar-dependent suppression of locomotion. Distinct receptor neurons for the same taste quality may coordinate early appetitive responses, taking advantage of the legs as the first appendages to contact food. PMID- 26893071 TI - Physical activity and non-movement behaviours: their independent and combined associations with metabolic syndrome. AB - BACKGROUND: Metabolic syndrome (MetS) is a prevalent risk condition associated with a higher risk of chronic conditions, including diabetes and cardiovascular diseases. Physical activity and non-movement behaviours (NMB), including sleep, screen time and sedentary activity, have been associated with MetS. In light of the increasing prevalence of NMBs, and the moderate rates of physical activity guideline adherence in Canada, this analysis examines the independent and combined associations of NMB and physical activity with MetS. METHODS: Data on Canadians 18 years and older from the Canadian Health Measures Survey (n = 2901) were used to examine the moderating effect of moderate-to-vigorous physical activity (MVPA) guideline adherence (150 minutes or more of MVPA/week, based on accelerometer) on the association of NMBs (sleep based on self-report, screen time based on self-report, and sedentary time based on accelerometer) with MetS. Logistic regression analyses were conducted and sampling weights were applied to represent the Canadian adult population. RESULTS: A graded association between PA and MetS was observed, with those achieving less MVPA than guidelines having a higher odds of MetS (OR 2.9, 95 % CI: 1.9-4.5 for < 75 mins/week of MVPA, and OR 1.8, 95 % CI: 1.2-2.8 for 75-150 mins/week, as compared to those accumulating 150 mins/week or more). When examining the moderating effect of PA on the association between NMBs and MetS, we found that (1) for participants who met guidelines, no level of any NMB was significantly associated with MetS and (2) for those who did not achieve guidelines, there was an increased odds of MetS based on excess NMB time(OR 3.2, 95 % CI: 1.5-6.8 for 1.4-2.1 h/day and OR 4.4, 95 % CI: 2.5-7.9 for >=2.1 h/day of screen time and 75-150 mins/week of MVPA, OR 1.7, 95 % CI: 1.1-2.5 for >=8 h/day of sleep time and <75 mins/week of MVPA, and OR 2.2, 95 % CI: 1.3 3.8 for 9.2-10.3 h/day of sedentary time and <75 mins/week of MVPA). CONCLUSIONS: Adhering to physical activity guidelines may mitigate the associations of NMBs with MetS. Given the novel findings that associations between NMBs and MetS were not significant among Canadians meeting PA guidelines, these results suggest the beneficial role of physical activity to prevent chronic disease risk. PMID- 26893074 TI - An integrative affect regulation process model of internalized weight bias and intuitive eating in college women. AB - The present study extended the weight stigma and well-being process model (Tylka et al., 2014) by examining three affect regulation pathways that may help simultaneously explain the predicted inverse association between internalized weight bias and intuitive eating. A weight-diverse sample of 333 college women completed an online survey assessing internalized weight stigma, intuitive eating, body shame, body image flexibility, and self-compassion. Self-reported height and weight were used to calculate body mass index (BMI). Non-parametric bootstrap resampling procedures were computed to ascertain the presence of the indirect effects of internalized weight bias on intuitive eating via the three hypothesized mediators controlling for BMI in a combined model. Results demonstrated that body image flexibility significantly and self-compassion marginally contributed unique variance in accounting for this relationship. Our preliminary cross-sectional findings contribute to a nascent body of scholarship seeking to provide a theoretically-driven understanding of how negative and positive forms of experiencing and relating to the body may co-occur within individuals. Results also point to potential target variables to consider incorporating in later-stage efforts to promote more adaptive ways of eating amidst internalized weight stigma. PMID- 26893072 TI - CMKLR1 deficiency maintains ovarian steroid production in mice treated chronically with dihydrotestosterone. AB - Elevated serum chemerin levels correlate with increased severity of polycystic ovary syndrome (PCOS). However, the role of CMKLR1 signaling in ovarian biology under conditions of excess DHT remains unclear. In this study we compared the effects of continuous 90-day high dose DHT exposure (83.3 ?g/day) on wild type and CMKLR1-deficient mice. DHT induced PCOS-like clinical signs in wild type mice as well as significant changes in the expression of hormone receptors, steroid synthesis enzymes, and BMPs and their receptors. In contrast, CMKLR1-deficient mice significantly attenuated DHT-induced clinical signs of PCOS and alterations in ovarian gene expression. To determine whether the BMP4 signaling pathway was involved in the pathogenic effects of CMKLR1 signaling in DHT-induced ovarian steroidogenesis, antral follicles were isolated from wild type and CMKLR1 knockout (KO) mice and treated in vitro with combinations of hCG, DHT, and BMP4 inhibitors. BMP4 inhibition attenuated the induction effects of hCG and DHT on estrogen and progesterone secretion in CMKLR1 KO mice, but not in WT mice, implicating the BMP4 signaling pathway in the CMKLR1-dependent response to DHT. In conclusion, CMKLR1 gene deletion attenuates the effects of chronic DHT treatment on ovarian function in experimental PCOS, likely via BMP4 signaling. PMID- 26893073 TI - Practical based approach to left main bifurcation stenting. AB - Despite the recent developments that have been made in the field of percutaneous left main (LM) intervention, the treatment of distal LM bifurcation remains challenging. The provisional one-stent approach for LM bifurcation has shown more favorable outcomes than the two-stent technique, making the former the preferred strategy in most types of LM bifurcation stenosis. However, elective two-stent techniques, none of which has been proven superior to the others, are still used in patients with severely diseased large side branches to avoid acute hemodynamic compromise. Selecting the proper bifurcation treatment strategy using meticulous intravascular ultrasound evaluation for side branch ostium is crucial for reducing the risk of side branch occlusion and for improving patient outcomes. In addition, unnecessary complex intervention can be avoided by measuring fractional flow reserve in angiographically isolated side branches. Most importantly, good long-term clinical outcomes are more related to the successful procedure itself than to the type of stenting technique, emphasizing the greater importance of optimizing the chosen technique than the choice of method. PMID- 26893075 TI - The relative stigmatization of eating disorders and obesity in males and females. AB - OBJECTIVE: Anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and obesity are stigmatized conditions known to affect both men and women. However, little research has examined differences in stigmatization of individuals with these diagnoses or the impact of gender on stigmatization. Such perceptions may play an important role in understanding and reducing the stigma associated with weight and dysfunctional eating behaviors. This study investigated stigmatizing attitudes toward eating disorders and obesity in men and women. METHOD: Participants were university undergraduates (N = 318; 73.6% female; mean age = 21.58 years, SD=3.97) who were randomly assigned to read one vignette describing a male or female target diagnosed with AN, BN, BED, or obesity. Participants then completed measures of stigma and perceived psychopathology. Measures were analyzed using a 4 (target diagnosis) x 2 (target gender) MANOVA and subsequent ANOVAs. RESULTS: Measures of stigma and perceived psychopathology revealed significant main effects for diagnosis (p < .001), but not for target gender. There were no interactions between target diagnosis and gender. Although all diagnostic conditions were stigmatized, more biased attitudes and perceptions of impairment were associated with targets with AN and BN compared to targets with BED and obesity. Additionally, individuals with AN, BN, and BED were perceived as having significantly more psychological problems and impairment than individuals with obesity. CONCLUSION: Although individuals with eating disorders and obesity both face stigmatizing attitudes, bias against individuals with AN, BN, and BED may exceed stigma toward obesity in the absence of binge eating. Future research is necessary to address stigmatizing beliefs to reduce and prevent discrimination against both men and women with eating disorders and obesity. PMID- 26893076 TI - Toxic epidermal necrolysis with isolated neutropenia related to the use of levetiracetam. PMID- 26893079 TI - High-throughput fluorescence microscopic analysis of protein abundance and localization in budding yeast. AB - Proteins directly carry out and regulate cellular functions. As a result, changes in protein levels within a cell directly influence cellular processes. Similarly, it is intuitive that the intracellular localization of proteins is a key component of their functionality. Optimal activity is achieved by a combination of protein concentration, co-compartmentalization with substrates, co-factors and regulators and sequestration from deleterious locales. The proteome within a cell is highly dynamic and changes in response to different environmental conditions. High-throughput microscopic analysis in the budding yeast Saccharomyces cerevisiae has afforded proteome-wide views of protein organization in living cells, and of how protein abundance and location is regulated and remodeled in response to stress. PMID- 26893080 TI - Food Proteins as Source of Opioid Peptides-A Review. AB - Traditional opioids, mainly alkaloids, have been used in the clinical management of pain for a number of years but are often associated with numerous side-effects including sedation, dizziness, physical dependence, tolerance, addiction, nausea, vomiting, constipation and respiratory depression which prevent their effective use. Opioid peptides derived from food provide significant advantages as safe and natural alternative due to the possibility of their production using animal and plant proteins as well as comparatively less side-effects. This review aims to discuss the current literature on food-derived opioid peptides focusing on their production, methods of detection, isolation and purification. The need for screening more dietary proteins as a source of novel opioid peptides is emphasized in order to fully understand their potential in pain management either as a drug or as part of diet complementing therapeutic prescription. PMID- 26893078 TI - Paediatric palliative care at home: a single centre's experience. AB - INTRODUCTION: There is increased awareness of paediatric palliative care in Malaysia, but no local published data on home care services. We aimed to describe the paediatric experience at Hospis Malaysia, a community-based palliative care provider in Malaysia. METHODS: We conducted a retrospective case note review of patients aged up to 21 years who were referred to Hospis Malaysia from 2009 to 2013. RESULTS: A total of 137 patients (92 male, 45 female) with a median age of 140 (3-250) months were included in this study. The majority (71.5%) had malignancies. At referral, 62 patients were still in hospital and 17 died prior to discharge. A total of 108 patients received home visits. At the first home visit, 89.8% of patients had at least one physical symptom. Pain was the most common (52.5%) symptom. Patients had various supportive devices: 39 were on feeding tubes, ten had tracheostomies, five were on bilevel positive airway pressure and ten had urinary catheters. 66 families discussed the preferred location of care at end-of-life. Among those who died, 78.9% died at home, as they preferred (p < 0.001). Regression analysis showed no statistically significant association between a home death and age, diagnosis and number of home visits. Bereavement follow-up occurred for 93.3% of families. CONCLUSION: Community care referrals tend to occur late, with 25.5% of patients dying within two weeks of referral. At referral, patients often had untreated physical symptoms. The majority of families preferred and had a home death. PMID- 26893082 TI - In situ sulfur isotopes (delta(34)S and delta(33)S) analyses in sulfides and elemental sulfur using high sensitivity cones combined with the addition of nitrogen by laser ablation MC-ICP-MS. AB - The sulfur isotope is an important geochemical tracer in diverse fields of geosciences. In this study, the effects of three different cone combinations with the addition of N2 on the performance of in situ S isotope analyses were investigated in detail. The signal intensities of S isotopes were improved by a factor of 2.3 and 3.6 using the X skimmer cone combined with the standard sample cone or the Jet sample cone, respectively, compared with the standard arrangement (H skimmer cone combined with the standard sample cone). This signal enhancement is important for the improvement of the precision and accuracy of in situ S isotope analysis at high spatial resolution. Different cone combinations have a significant effect on the mass bias and mass bias stability for S isotopes. Poor precisions of S isotope ratios were obtained using the Jet and X cones combination at their corresponding optimum makeup gas flow when using Ar plasma only. The addition of 4-8 ml min(-1) nitrogen to the central gas flow in laser ablation MC-ICP-MS was found to significantly enlarge the mass bias stability zone at their corresponding optimum makeup gas flow in these three different cone combinations. The polyatomic interferences of OO, SH, OOH were also significantly reduced, and the interference free plateaus of sulfur isotopes became broader and flatter in the nitrogen mode (N2 = 4 ml min(-1)). However, the signal intensity of S was not increased by the addition of nitrogen in this study. The laser fluence and ablation mode had significant effects on sulfur isotope fractionation during the analysis of sulfides and elemental sulfur by laser ablation MC-ICP-MS. The matrix effect among different sulfides and elemental sulfur was observed, but could be significantly reduced by line scan ablation in preference to single spot ablation under the optimized fluence. It is recommended that the d90 values of the particles in pressed powder pellets for accurate and precise S isotope analysis should be less than 10 MUm. Under the selected optimized analytical conditions, excellent agreements between the determined values and the reference values were achieved for the IAEA-S series standard reference materials and a set of six well-characterized, isotopic homogeneous sulfide standards (PPP-1, MoS2, MASS-1, P-GBW07267, P-GBW07268, P-GBW07270), validating the capability of the developed method for providing high-quality in situ S isotope data in sulfides and elemental sulfur. PMID- 26893077 TI - Basal ganglia correlates of fatigue in young adults. AB - Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward. PMID- 26893081 TI - A review of recent methods for the determination of ranges of feasible solutions resulting from soft modelling analyses of multivariate data. AB - Soft modelling or multivariate curve resolution (MCR) are well-known methodologies for the analysis of multivariate data in many different application fields. Results obtained by soft modelling methods are very likely impaired by rotational and scaling ambiguities, i.e. a full range of feasible solutions can describe the data equally well while fulfilling the constraints of the system. These issues are severely limiting the applicability of these methods and therefore, they can be considered as the most challenging ones. The purpose of the current review is to describe and critically compare the available methods that attempt at determining the range of ambiguity for the case of 3-component systems. Theoretical and practical aspects are discussed, based on a collection of simulated examples containing noise-free and noisy data sets as well as an experimental example. PMID- 26893083 TI - Variable importance analysis based on rank aggregation with applications in metabolomics for biomarker discovery. AB - Biomarker discovery is one important goal in metabolomics, which is typically modeled as selecting the most discriminating metabolites for classification and often referred to as variable importance analysis or variable selection. Until now, a number of variable importance analysis methods to discover biomarkers in the metabolomics studies have been proposed. However, different methods are mostly likely to generate different variable ranking results due to their different principles. Each method generates a variable ranking list just as an expert presents an opinion. The problem of inconsistency between different variable ranking methods is often ignored. To address this problem, a simple and ideal solution is that every ranking should be taken into account. In this study, a strategy, called rank aggregation, was employed. It is an indispensable tool for merging individual ranking lists into a single "super"-list reflective of the overall preference or importance within the population. This "super"-list is regarded as the final ranking for biomarker discovery. Finally, it was used for biomarkers discovery and selecting the best variable subset with the highest predictive classification accuracy. Nine methods were used, including three univariate filtering and six multivariate methods. When applied to two metabolic datasets (Childhood overweight dataset and Tubulointerstitial lesions dataset), the results show that the performance of rank aggregation has improved greatly with higher prediction accuracy compared with using all variables. Moreover, it is also better than penalized method, least absolute shrinkage and selectionator operator (LASSO), with higher prediction accuracy or less number of selected variables which are more interpretable. PMID- 26893084 TI - Enhanced target factor analysis. AB - Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets. PMID- 26893085 TI - Toward automated chromatographic fingerprinting: A non-alignment approach to gas chromatography mass spectrometry data. AB - In contrast to targeted analysis of volatile compounds, non-targeted approaches take information of known and unknown compounds into account, are inherently more comprehensive and give a more holistic representation of the sample composition. Although several non-targeted approaches have been developed, there's still a demand for automated data processing tools, especially for complex multi-way data such as chromatographic data obtained from multichannel detectors. This work was therefore aimed at developing a data processing procedure for gas chromatography mass spectrometry (GC-MS) data obtained from non-targeted analysis of volatile compounds. The developed approach uses basic matrix manipulation of segmented GC MS chromatograms and PARAFAC multi-way modelling. The approach takes retention time shifts and peak shape deformations between samples into account and can be done with the freely available N-way toolbox for MATLAB. A demonstration of the new fingerprinting approach is presented using an artificial GC-MS data set and an experimental full-scan GC-MS data set obtained for a set of experimental wines. PMID- 26893087 TI - Flow method based on cloud point extraction for fluorometric determination of epinephrine in human urine. AB - A novel stepwise injection fluorometric method for the determination of epinephrine in human urine has been developed. In the current study, the stepwise injection analysis (SWIA) was successfully combined with on-line in-syringe cloud point extraction (CPE) and fluorometric detection. The procedure was based on the epinephrine derivatization in the presence of o-phenylenediamine followed by the preconcentration stage based on the CPE with the nonionic surfactant Triton X 114. After the phase separation into a syringe of the flow system, the micellar phase containing the epinephrine derivative was transported to a fluorometric detector. The excitation and emission wavelengths were set at 447 nm and 550 nm, respectively. The conditions of epinephrine derivatization and CPE have been studied. The calibration plot constructed using the developed procedure was linear in the range of 1.10(-11)-5.10(-7) mol L(-1). The limit of detection, calculated as 3 sigma of a blank test (n = 10), was found to be 3.10(-12) mol L( 1). The proposed method was successfully applied for the determination of epinephrine in human urine samples. PMID- 26893088 TI - MSFIA-LOV system for (226)Ra isolation and pre-concentration from water samples previous radiometric detection. AB - An automatic system based on multisyringe flow injection analysis (MSFIA) and lab on-valve (LOV) flow techniques for separation and pre-concentration of (226)Ra from drinking and natural water samples has been developed. The analytical protocol combines two different procedures: the Ra adsorption on MnO2 and the BaSO4 co-precipitation, achieving more selectivity especially in water samples with low radium levels. Radium is adsorbed on MnO2 deposited on macroporous of bead cellulose. Then, it is eluted with hydroxylamine to transform insoluble MnO2 to soluble Mn(II) thus freeing Ra, which is then coprecipitated with BaSO4. The (226)Ra can be directly detected in off-line mode using a low background proportional counter (LBPC) or through a liquid scintillation counter (LSC), after performing an on-line coprecipitate dissolution. Thus, the versatility of the proposed system allows the selection of the radiometric detection technique depending on the detector availability or the required response efficiency (sample number vs. response time and limit of detection). The MSFIA-LOV system improves the precision (1.7% RSD), and the extraction frequency (up to 3 h(-1)). Besides, it has been satisfactorily applied to different types of water matrices (tap, mineral, well and sea water). The (226)Ra minimum detectable activities (LSC: 0.004 Bq L(-1); LBPC: 0.02 Bq L(-1)) attained by this system allow to reach the guidance values proposed by the relevant international agencies e.g. WHO, EPA and EC. PMID- 26893086 TI - An intimately bonded titanate nanotube-polyaniline-gold nanoparticle ternary composite as a scaffold for electrochemical enzyme biosensors. AB - In this work, titanate nanotubes (TNTs), polyaniline (PANI) and gold nanoparticles (GNPs) were assembled to form a ternary composite, which was then applied on an electrode as a scaffold of an electrochemical enzyme biosensor. The scaffold was constructed by oxidatively polymerising aniline to produce an emeraldine salt of PANI on TNTs, followed by gold nanoparticle deposition. A novel aspect of this scaffold lies in the use of the emeraldine salt of PANI as a molecular wire between TNTs and GNPs. Using horseradish peroxidase (HRP) as a model enzyme, voltammetric results demonstrated that direct electron transfer of HRP was achieved at both TNT-PANI and TNT-PANI-GNP-modified electrodes. More significantly, the catalytic reduction current of H2O2 by HRP was ~75% enhanced at the TNT-PANI-GNP-modified electrode, compared to that at the TNT-PANI-modified electrode. The heterogeneous electron transfer rate constant of HRP was found to be ~3 times larger at the TNT-PANI-GNP-modified electrode than that at the TNT PANI-modified electrode. Based on chronoamperometric detection of H2O2, a linear range from 1 to 1200 MUM, a sensitivity of 22.7 MUA mM(-1) and a detection limit of 0.13 MUM were obtained at the TNT-PANI-GNP-modified electrode. The performance of the biosensor can be ascribed to the superior synergistic properties of the ternary composite. PMID- 26893089 TI - Application of direct-injection detector integrated with the multi-pumping flow system to chemiluminescence determination of the total polyphenol index. AB - In this work, we present a novel chemiluminescence (CL) method based on direct injection detector (DID) integrated with the multi-pumping flow system (MPFS) to chemiluminescence determination of the total polyphenol index. In this flow system, the sample and the reagents are injected directly into the cone-shaped detection cell placed in front of the photomultiplier window. Such construction of the detection chamber allows for fast measurement of the CL signal in stopped flow conditions immediately after mixing the reagents. The proposed DID-CL-MPFS method is based on the chemiluminescence of nanocolloidal manganese(IV) hexametaphosphate-ethanol system. The application of ethanol as a sensitizer, eliminated the use of carcinogenic formaldehyde. Under the optimized experimental conditions, the chemiluminescence intensities are proportional to the concentration of gallic acid in the range from 5 to 350 ng mL(-1). The DID-CL MPFS method offers a number of advantages, including low limit of detection (0.80 ng mL(-1)), high precision (RSD = 3.3%) and high sample throughput (144 samples h(-1)) as well as low consumption of reagents, energy and low waste generation. The proposed method has been successfully applied to determine the total polyphenol index (expressed as gallic acid equivalent) in a variety of plant derived food samples (wine, tea, coffee, fruit and vegetable juices, herbs, spices). PMID- 26893090 TI - Determination of creatinine-related molecules in saliva by reversed-phase liquid chromatography with tandem mass spectrometry and the evaluation of hemodialysis in chronic kidney disease patients. AB - The serum concentrations of creatinine (Cre) and urea are used for the determination of the renal function. However, the use of blood is not always suitable due to the invasive, hygienic and infection problems during its sample collection and handling. In contrast, saliva is relatively clean and the samples can be quickly and noninvasively collected and easily stored. Therefore, the simultaneous determination of Arginine (Arg), creatine (Cr) and Cre in the saliva of chronic kidney disease (CKD) patients was performed by UPLC-ESI-MS/MS together with the saliva of healthy volunteers. The evaluation of hemodialysis of CKD patients was also carried out by the determinations before and after the dialysis. An HS-F5 column was used for the simultaneous determination of Arg, Cr and Cre in the saliva. These molecules were rapidly separated within 4 min and sensitively determined by the multiple reaction monitoring (MRM) of the precursor ion [M+H](+) -> product ions (m/z 175.1 -> 70.1 for Arg; m/z 132.0 -> 44.1 for Cr; m/z 114.0 -> 44.1 for Cre). The concentration of Cre in the CKD patients was higher than that in the healthy persons. The concentrations of Cre in the saliva of the patients before hemodialysis were moderately correlated with the serum Cre concentrations (R(2) = 0.661). Furthermore, the concentration in the saliva obviously decreased after hemodialysis (before 0.73 mg/dL, after 0.25 mg/dL; p < 0.02). Thus, the proposed detection method using saliva by UPLC-MS/MS is useful for the evaluation of the renal function in CKD patients. The present method offers a new option for monitoring the hemodialysis of CKD patients. PMID- 26893091 TI - Elucidating the structure of carbon nanoparticles by ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry. AB - A fast and accurate ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (UPLC ESI-Q-TOF-MS/MS) method was developed for the separation and structural elucidation of fluorescent carbon nanoparticles (CNP). The CNP was synthesised from microwave-assisted pyrolysis of citric acid (CA) and 1,2-ethylenediamine (EDA). By using UPLC separation, the CNP product was well separated into ten fractions within 4.0 min. Based on high-accuracy MS and MS/MS analyses, the CNP species were revealed to display six kinds of chemical formulas, including (C10H20N4O5)n, (C8H12N2O5)n, (C16H22N4O9)n, (C6H8O7)n, (C14H18N2O11)n, and (C14H16N2O10)n. In particular, our study revealed for the first time that the CNP species exist as supramolecular clusters with their individual monomers units linked together through non-covalent bonding forces. These findings clearly indicated the usefulness of UPLC-ESI-Q-TOF-MS/MS in identifying the chemical composition of CNP product. It is anticipated that our proposed methodology can be applied to study the structure-property relationships of CNP, facilitating in the production of CNP with desirable spectral features. PMID- 26893092 TI - Novel redox species polyaniline derivative-Au/Pt as sensing platform for label free electrochemical immunoassay of carbohydrate antigen 199. AB - A novel electrochemical redox-active nanocomposite was synthesized by a one-pot method using N,N'-diphenyl-p-phenylediamine as monomer, and HAuCl4 and K2PtCl4 as co-oxidizing agents. The as-prepared poly(N,N'-diphenyl-p-phenylediamine)-Au/Pt exhibited admirable electrochemical redox activity at 0.15 V, excellent H2O2 electrocatalytic ability and favorable electron transfer ability. Based on these, the evaluation of the composite as sensing substrate for label-free electrochemical immunosensing to the sensitive detection of carbohydrate antigen 199 was described. This technique proved to be a prospective detection tool with a wide liner range from 0.001 U mL(-1) to 40 U mL(-1), and a low detection limit of 2.3 * 10(-4) U mL(-1) (S/N = 3). In addition, this method was used for the analysis of human serum sample, and good agreement was obtained between the values and those of enzyme-linked immunosorbent assay, implying the potential application in clinical research. Importantly, the strategy of the present substrate could be extended to other polymer-based nanocomposites such as polypyrrole derivatives or polythiophene derivatives, and this could be of great significance for the electrochemical immunoassay. PMID- 26893093 TI - Development of a BODIPY-based ratiometric fluorescent probe for hypochlorous acid and its application in living cells. AB - A BODIPY-based ratiometric fluorescent probe for HOCl has been designed based on the transduction of thioether to sulfoxide function. This probe features a marked absorption and emission blue-shift upon the HOCl-promoted rapid transduction, enabling the highly selective and ratiometric detection. In addition, the probe works excellently within a wide pH range of 4-10, addressing the existing pH dependency issue. Living cells studies demonstrate that the probe is cell membrane permeable and can be employed successfully to image endogenous HOCl generation in macrophage cells. PMID- 26893094 TI - Triple-channel portable capillary electrophoresis instrument with individual background electrolytes for the concurrent separations of anionic and cationic species. AB - The portable capillary electrophoresis instrument is automated and features three independent channels with different background electrolytes to allow the concurrent optimized determination of three different categories of charged analytes. The fluidic system is based on a miniature manifold which is based on mechanically milled channels for injection of samples and buffers. The planar manifold pattern was designed to minimize the number of electronic valves required for each channel. The system utilizes pneumatic pressurization to transport solutions at the grounded as well as the high voltage side of the separation capillaries. The instrument has a compact design, with all components arranged in a briefcase with dimensions of 45 (w) * 35 (d) * 15 cm (h) and a weight of about 15 kg. It can operate continuously for 8 h in the battery-powered mode if only one electrophoresis channel is in use, or for about 2.5 h in the case of simultaneous employment of all three channels. The different operations, i.e. capillary flushing, rinsing of the interfaces at both capillary ends, sample injection and electrophoretic separation, are activated automatically with a control program featuring a graphical user interface. For demonstration, the system was employed successfully for the concurrent separation of different inorganic cations and anions, organic preservatives, additives and artificial sweeteners in various beverage and food matrices. PMID- 26893095 TI - Angiographic patterns of drug-eluting stent restenosis after treatment with drug coated balloon versus balloon angioplasty: Late lumen loss subgroup analyses of the PEPCAD-DES study. AB - OBJECTIVES: This report provides the results of additional late lumen loss (LLL) analyses the predefined subgroup of diabetics and post hoc analyses of selected lesion morphologies to further elucidate the efficacy of paclitaxel coated balloon (PCB) angioplasty (clinical trials identifier NCT00998439). BACKGROUND: The PEPCAD-DES trial revealed that in lesion LLL and the target lesion revascularization rate (TLR) were significantly reduced with PCB angioplasty as compared with plain old balloon angioplasty (POBA) in patients with drug-eluting stent restenosis (DES-ISR). METHODS: A total of 110 patients with restenosis of Sirolimus- (SES), Everolimus- (EES), or Paclitaxel-eluting (PES) stents in native coronary arteries were randomized 2:1 to receive treatment with PCB (72 patients) or POBA (38 patients). RESULTS: In the PCB group, LLL did not differ for PES versus non-PES lesions (0.46 +/- 0.55 mm vs. 0.41 +/- 0.65 mm, P = 0.81). Moreover, there was no difference in LLL when PCB's were used in single and multiple layer DES-ISR (0.35 +/- 0.60 mm vs. 0.51 +/- 0.63 mm, P = 0.31). In contrast, patients treated with POBA for multilayer DES-ISR were more likely to have significantly higher LLL as compared with single layer DES-ISR (1.29 +/- 0.76 mm vs. 0.65 +/- 0.60 mm, P = 0.02). There was no LLL difference between diabetics and non-diabetics when treated with PCB angioplasty (0.46 +/- 0.76 mm vs. 0.43 +/- 0.54 mm, P = 0.83). CONCLUSION: Our hypothesis generating results indicated that there were no differences in terms of LLL when PCB angioplasty was applied in subgroups of single versus multiple layer DES-ISR and PES-ISR versus non-PES ISR. LLL was not higher in diabetic patients as compared with the their non-diabetic counterparts when treated with PCB's. (c) 2016 Wiley Periodicals, Inc. PMID- 26893097 TI - Erratum to: Effect of Training Leading to Repetition Failure on Muscular Strength: A Systematic Review and Meta-Analysis. PMID- 26893096 TI - Women-only drug treatment services and needs in Iran: the first review of current literature. AB - BACKGROUND: Iran (Persia) has a women-only drug treatment system. However, literature is not documented. The current study aimed to review the development of women-only drug treatment and harm reduction services (WODTHRS) and the factors associated with treatment entry and outcomes in Iran. The review was based on a comprehensive search for all literature focusing on WODTHRS in Iran. METHODS: Data were collected by conducting systematic searching of scientific English and Persian databases and grey literature. This was done in line with Cochrane Guideline for conducting systematic reviews. Overall, 19,929 studies were found. But, only 19 original studies were included after excluding non relevant studies. RESULTS: The review findings indicate how WODTHRS have been developed in the past 15 years. The review findings underscore the roles of numerous factors in treatment entry such as the side effects of illicit drug use. In addition, cognitive-behavioral interventions, methadone treatment and some factors outside drug treatment such as family support increase positive treatment outcomes among women. In contrast, financial problems as well as other factors such as insufficient medical, psychiatric and social work services hamper treatment entry and positive treatment outcomes. CONCLUSIONS: The review results highlight that eliminating barriers to treatment entry and positive treatment outcomes should be addressed. Conducting randomized controlled trials is needed to evaluate the effectiveness of WODTHRS. This issue should address the factors influencing service utilization to incorporate the best practice for women. The evaluation of the long-term efficacy of WODTHRS is a critical research gap which should be addressed in future studies. PMID- 26893099 TI - Utility of Exercise Electrocardiography in Pre-participation Screening in Asymptomatic Athletes: A Systematic Review. AB - BACKGROUND: Although test characteristics of exercise electrocardiography are well established in symptomatic patients, data on healthy athletes are scarce. This systematic review focuses on the diagnostic utility of exercise electrocardiography for the detection of coronary heart disease in athletes during pre-participation screening. OBJECTIVES: This systematic review evaluated the prevalence of an abnormal exercise test result and the positive predictive value of exercise electrocardiography in asymptomatic athletes. In addition, the long-term prognosis of a false-positive test result was evaluated. METHODS: An electronic search was performed using the Cochrane Library, PubMed, and MEDLINE. Only studies using exercise electrocardiography in an unselected population of asymptomatic athletes were included. Data on population characteristics, cardiovascular risk factors, exercise test parameters, left ventricular hypertrophy, and morbidity/mortality were extracted and analyzed. RESULTS: The mean prevalence of an abnormal exercise test result was 0.6 % (range 0-29 %), with a positive predictive value of 9 % (range 0-55 %). Left ventricular hypertrophy was observed in 57 % of the athletes with an abnormal exercise test result, in 50 % of the athletes with a false-positive exercise test result, and in 24 % of the athletes with a normal exercise test. Among athletes with a false positive test, only one athlete (3 %) experienced a possible cardiac event. CONCLUSION: This systematic review revealed a relatively low prevalence of positive exercise test results in asymptomatic athletes, but a very poor positive predictive value. There were insufficient data available to determine the prognostic implications of false-positive test results in asymptomatic athletes. PMID- 26893101 TI - Household food insecurity, nutritional status and morbidity in Brazilian children. AB - OBJECTIVE: To identify the association of household food insecurity (HFI) with anthropometric status, the risk of vitamin A deficiency and anaemia, morbidities such as cough and fever, and hospitalizations for diarrhoea and pneumonia in children under 5 years old. DESIGN: Cross-sectional study using data from the 2006 Brazilian Demographic and Health Survey. HFI was measured with the Brazilian Food Insecurity Measurement Scale (EBIA). Vitamin A deficiency and anaemia were assessed in blood samples. Child morbidities were reported by the child's mother and included cough, fever, and hospitalizations for diarrhoea and pneumonia. Regression results were expressed as unadjusted and adjusted OR and corresponding 95 % CI for severe food insecurity, with statistical significance set at P<0.05. SETTING: Nationally representative survey. SUBJECTS: Children (n 4064) under 5 years old. RESULTS: There was no association between HFI and vitamin A deficiency, pneumonia, wasting or overweight. The prevalence of cough, fever, hospitalization for diarrhoea and stunting were associated with degree of HFI severity. There was a significant association of morbidities and stunting with severe food insecurity (v. food secure). After controlling for confounders, the association between severe food insecurity (v. food secure/rest of food insecurity categories) and the prevalence of common morbidities remained strong, showing that severely food-insecure children had a greater likelihood of experiencing cough (adjusted OR=1.79) and of being hospitalized for diarrhoea (adjusted OR=2.55). CONCLUSIONS: Severe HFI was associated with cough and severe diarrhoea among Brazilian children. PMID- 26893100 TI - Vasohibin-1 expression inhibits advancement of ovarian cancer producing various angiogenic factors. AB - Vasohibin-1 (VASH1) is a negative feedback regulator of angiogenesis, the first to be discovered, and was identified in vascular endothelial growth factor (VEGF) stimulated vascular endothelial cells. Vasohibin-1 inhibits abnormal vascularization induced by various angiogenic factors including fibroblast growth factor and platelet-derived growth factor (PDGF), in addition to VEGF. By focusing on this characteristic of VASH1, we investigated the antitumor effects of VASH1 expression on ovarian cancer cells that produce different angiogenic factors. By using a high VEGF-producing ovarian cancer cell line, SHIN-3, and a high PDGF-producing ovarian cancer cell line, KOC-2S, the cells were transfected with either a VEGF antagonist, soluble VEGF receptor-1 (sVEGFR-1, or sFlt-1), or VASH1 genes to establish their respective cellular expression. The characteristics of these transfectants were compared with controls. We previously reported that the expression of sFlt-1 inhibited tumor vascularization and growth of high VEGF-producing ovarian cancer cells, reduced peritoneal dissemination and ascites development, and prolonged the survival time of the host. However, in the current study, the expression of sFlt-1 had no such effect on the high PDGF producing ovarian cancer cells used here, whereas VASH1 expression inhibited tumor vascularization and growth, not only in high VEGF-producing cells, but also in high PDGF-producing cells, reduced their peritoneal dissemination and ascites, and prolonged the survival time of the host. These results suggest that VASH1 is an effective treatment for ovarian cancer cells that produce different angiogenic factors. PMID- 26893098 TI - Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions. AB - BACKGROUND: The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise training interventions aimed at improving function and maintaining independence in later life. OBJECTIVES: The objectives of this review were to (1) systematically review the relationship between muscle power and functional performance in older people; (2) systematically review the effect of power training (PT) interventions on functional performance in older people; and (3) identify components of successful PT interventions relevant to pragmatic trials by scoping the literature. METHODS: Our approach involved three stages. First, we systematically reviewed evidence on the relationship between muscle power, muscle strength and functional performance and, second, we systematically reviewed PT intervention studies that included both muscle power and at least one index of functional performance as outcome measures. Finally, taking a strong pragmatic perspective, we conducted a scoping review of the PT evidence to identify the successful components of training interventions needed to provide a minimally effective training dose to improve physical function. RESULTS: Evidence from 44 studies revealed a positive association between muscle power and indices of physical function, and that muscle power is a marginally superior predictor of functional performance than muscle strength. Nine studies revealed maximal angular velocity of movement, an important component of muscle power, to be positively associated with functional performance and a better predictor of functional performance than muscle strength. We identified 31 PT studies, characterised by small sample sizes and incomplete reporting of interventions, resulting in less than one-in-five studies judged as having a low risk of bias. Thirteen studies compared traditional resistance training with PT, with ten studies reporting the superiority of PT for either muscle power or functional performance. Further studies demonstrated the efficacy of various methods of resistance and functional task PT on muscle power and functional performance, including low-load PT and low-volume interventions. CONCLUSIONS: Maximal intended movement velocity, low training load, simple training methods, low-volume training and low-frequency training were revealed as components offering potential for the development of a pragmatic intervention. Additionally, the research area is dominated by short-term interventions producing short-term gains with little consideration of the long-term maintenance of functional performance. We believe the area would benefit from larger and higher-quality studies and consideration of optimal long-term strategies to develop and maintain muscle power and physical function over years rather than weeks. PMID- 26893102 TI - A random graph model of density thresholds in swarming cells. AB - Swarming behaviour is a type of bacterial motility that has been found to be dependent on reaching a local density threshold of cells. With this in mind, the process through which cell-to-cell interactions develop and how an assembly of cells reaches collective motility becomes increasingly important to understand. Additionally, populations of cells and organisms have been modelled through graphs to draw insightful conclusions about population dynamics on a spatial level. In the present study, we make use of analogous random graph structures to model the formation of large chain subgraphs, representing interactions between multiple cells, as a random graph Markov process. Using numerical simulations and analytical results on how quickly paths of certain lengths are reached in a random graph process, metrics for intercellular interaction dynamics at the swarm layer that may be experimentally evaluated are proposed. PMID- 26893103 TI - The role of Card9 overexpression in peripheral blood mononuclear cells from patients with aseptic acute pancreatitis. AB - Activated mononuclear cells are an early event in the course of severe acute pancreatitis (SAP). To date, the molecular mechanism triggering peripheral blood mononuclear cells (PBMCs) is poorly understood. The aim of this paper was to determine the potential role of Card9 in SAP. We collected data from 72 subjects between January 2013 and June 2014. Subsequently, PBMCs were isolated on day 1, 3 and 5 of pancreatitis. Immunofluorescence staining, quantitative real-time PCR, Western blotting, immunoprecipitation and ELISA were used to determine the role of Card9 in SAP. Microbial culture showed that SAP patients at the early period did not develop any bacteria and fungi infection. Card9 expression in SAP patients was higher than that in mild acute pancreatitis and volunteer healthy controls, up to the peak on day 1. The monocyte-derived cytokines interleukin (IL)-17, IL-1beta, IL-6 and tumour necrosis factor-alpha mediated by the induction of Card9 markedly increased in SAP patients compared with the control group. Furthermore, the inducible formation of Card9-Bcl10 complex was found in PBMCs, which may be involved in nuclear factor kappa B (NF-kappaB) and p38 activation in SAP. Receiver operating characteristic curve indicated that Card9 levels had a high sensitivity of 87.5% and specificity of 67.7%, showing the close correlation with SAP patients. Card9 overexpression was firstly found in aseptic SAP, which may be played an important role in NF-kappaB and p38 activation in PBMCs. It also provided the new insights into therapeutic interventions by targeting monocytes activation in SAP patients. PMID- 26893105 TI - A clinical validation study for application of DBS in therapeutic drug monitoring of antidepressants. AB - BACKGROUND: A bridging study of plasma and DBS concentrations for therapeutic drug monitoring of antidepressants was performed. RESULTS & METHODOLOGY: Potassium-based hematocrit analysis was included. In addition, we defined acceptance criteria based on the differences between individual data points of plasma and DBS concentrations. These criteria were applied to test acceptability of error found in predicted nortriptyline plasma concentrations. Potassium-based hematocrit predicted a negative bias for DBS concentrations of amitriptyline, but not for the other compounds. To predict plasma concentrations of antidepressants based on DBS concentrations, a factor of 0.8, 0.65, 0.84 and 0.78 was found for nortriptyline, desmethylclomipramine, venlafaxine and desmethylvenlafaxine, respectively. DISCUSSION & CONCLUSION: Application of the factor and newly formulated acceptance criteria demonstrated prediction of nortriptyline plasma concentrations based on DBS concentrations. PMID- 26893104 TI - Retinal Ganglion Cell Loss is Delayed Following Optic Nerve Crush in NLRP3 Knockout Mice. AB - The NLRP3 inflammasome, a sensor for a variety of pathogen- and host-derived threats, consists of the adaptor ASC (Apoptosis-associated Speck-like protein containing a Caspase Activation and Recruitment Domain (CARD)), pro-caspase-1, and NLRP3 (NOD-Like Receptor family Pyrin domain containing 3). NLRP3-induced neuroinflammation is implicated in the pathogenesis and progression of eye diseases, but it remains unclear whether activation of NLRP3 inflammasome contributes to retinal ganglion cell (RGC) death. Here we examined NLRP3-induced neuroinflammation and RGC survival following partial optic nerve crush (pONC) injury. We showed that NLRP3 was up-regulated in retinal microglial cells following pONC, propagating from the injury site to the optic nerve head and finally the entire retina within one day. Activation of NLRP3-ASC inflammasome led to the up-regulation of caspase-1 and a proinflammatory cytokine, interleukin 1beta (IL-1beta). In NLRP3 knockout mice, up-regulation of ASC, caspase-1, and IL 1beta were all reduced, and, importantly, RGC and axon loss was substantially delayed following pONC injury. The average survival time of RGCs in NLRP3 knockout mice was about one week longer than for control animals. Taken together, our study demonstrated that ablating the NLRP3 gene significantly reduced neuroinflammation and delayed RGC loss after optic nerve crush injury. PMID- 26893106 TI - Graphene quantum dots as additives in capillary electrophoresis for separation cinnamic acid and its derivatives. AB - A facile capillary electrophoresis (CE) method for the separation of cinnamic acid and its derivatives (3,4-dimethoxycinnamic acid, 4-methoxycinnamic acid, isoferulic acid, sinapic acid, cinnamic acid, ferulic acid, and trans-4 hydroxycinnamic acid) using graphene quantum dots (GQDs) as additives with direct ultraviolet (UV) detection is reported. GQDs were synthesized by chemical oxidization and further purified by a macroporous resin column to remove salts (Na2SO4 and NaNO3) and other impurities. Transmission electron microscopy (TEM) indicated that GQDs have a relatively uniform particle size (2.3 nm). Taking into account the structural features of GQDs, cinnamic acid and its derivatives were adopted as model compounds to investigate whether GQDs can be used to improve CE separations. The separation performance of GQDs used as additives in CE was studied through variations of pH, concentration of the background electrolyte (BGE), and contents of GQDs. The results indicated that excellent separation can be achieved in less than 18 min, which is mainly attributed to the interaction between the analytes and GQDs, especially isoferulic acid, sinapic acid, and cinnamic acid. PMID- 26893107 TI - SMART DigestTM compared with pellet digestion for analysis of human immunoglobulin G1 in rat serum by liquid chromatography tandem mass spectrometry. AB - The newly developed SMART DigestTM kit was applied for the sample preparation of human immunoglobulin G1 (hIgG1) in rat serum prior to qualitative and quantitative analyses by liquid chromatography tandem mass spectrometry (LC MS/MS). The sequence coverages obtained for the light and heavy chains of hIgG1A were 50 and 76%, respectively. The calibration curve was linear from 1.00 to 1000 MUg/ml for three of four generic peptides. Overall, the SMART DigestTM kit resulted in similar quantitative data (linearity, sensitivity, accuracy, and precision) compared with the pellet digestion protocol. However, the SMART DigestTM required only 2 h of sample preparation with fewer reagents. PMID- 26893108 TI - Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure. AB - BACKGROUND: Noninvasive diagnosis of pulmonary hypertension (PH) primarily relies upon Doppler echocardiography of tricuspid regurgitation (TR). However, TR might be absent or difficult to measure. HYPOTHESIS/OBJECTIVES: To determine the diagnostic value of right pulmonary artery distensibility (RPAD) index for prediction of Doppler-derived estimates of pulmonary artery (PA) pressure compared to other indices of PH in dogs. ANIMALS: Sixty-nine client-owned dogs with TR. METHODS: Prospective observational study. Dogs were allocated to groups according to TR pressure gradient (TRPG): TRPG <36 mmHg (control, n = 22), TRPG 36-50 (n = 16), TRPG 50-75 (n = 14) and TRPG >75 mmHg (n = 17). Right pulmonary artery distensibility index, acceleration time to peak PA flow (AT), AT: ejection time of PA flow (AT:ET) and main PA size: aorta size (MPA:Ao) were calculated in each dog. RESULTS: Right pulmonary artery distensibility index demonstrated the strongest correlation (r = -0.90; P < .0001) to TRPG followed by MPA:Ao (r = 0.78; P < .0001), AT (r = -0.69; P < .0001) and AT:ET (r = -0.68; P < .0001). RPAD index possessed the most accurate cutoff (<29.5%; Sensitivity [Sn] 0.84, Specificity [Sp] 0.95) to predict TRPG >50 mmHg compared to AT (<53.9 ms; Sn 0.74, Sp 0.87), AT:ET (<0.30; Sn 0.61, Sp 0.97) and MPA:Ao (>1.04; Sn 0.94, Sp 0.74). All intra- and interobserver measurement variabilities exhibited coefficients of variation <=13%. CONCLUSIONS AND CLINICAL IMPORTANCE: Right pulmonary artery distensibility index is an accurate predictor of TRPG and should be particularly useful if TR is absent or difficult to measure. PMID- 26893109 TI - Thermal electron-tunneling devices as coolers and amplifiers. AB - Nanoscale thermal systems that are associated with a pair of electron reservoirs have been previously studied. In particular, devices that adjust electron tunnels relatively to reservoirs' chemical potentials enjoy the novelty and the potential. Since only two reservoirs and one tunnel exist, however, designers need external aids to complete a cycle, rendering their models non-spontaneous. Here we design thermal conversion devices that are operated among three electron reservoirs connected by energy-filtering tunnels and also referred to as thermal electron-tunneling devices. They are driven by one of electron reservoirs rather than the external power input, and are equivalent to those coupling systems consisting of forward and reverse Carnot cycles with energy selective electron functions. These previously-unreported electronic devices can be used as coolers and thermal amplifiers and may be called as thermal transistors. The electron and energy fluxes of devices are capable of being manipulated in the same or oppsite directions at our disposal. The proposed model can open a new field in the application of nano-devices. PMID- 26893111 TI - Epiduroscopic Laser Neural Decompression for Removal of L2-3 Disc Herniation in a Patient with Symptoms Suggestive of L5 Nerve Root Involvement. PMID- 26893110 TI - Translation, Adaptation, and Validation of Hindi Version of the Pain Catastrophizing Scale in Patients with Chronic Low Back Pain for Use in India. AB - OBJECTIVES : This study translates the Pain Catastrophizing Scale (PCS) into Hindi and examines the psychometric properties of the translated version (Hindi PCS [Hi-PCS]) in patients with chronic low back pain (CLBP). METHODS : Forward and backward translations were performed from English to Hindi according to standard methodology. A final version was evaluated by a committee of clinical experts and Hi-PCS was then pilot-tested in 10 patients with CLBP. Cross-cultural validation of the resulting adapted Hi-PCS was done by administering Hi-PCS at baseline to 100 patients with CLBP (>= 12 weeks pain) who were able to read and write in Hindi, and re-administering Hi-PCS after 3 days. Construct validity was assessed using factor analysis. Psychometric properties including internal consistency; test-retest reliability; and convergent validity with pain severity, functional disability, and health-related quality of life (HRQoL) were also assessed. RESULTS : Principal component analysis observed a three-factor structure, which explained 58% of the variance. Confirmatory factor analysis elicited the best fit as judged by the model fit indices. Hi-PCS as a whole was deemed to be internally consistent (Cronbach's alpha = 0.76). Intraclass correlation coefficient for the Hi-PCS is 0.923 (95% CI: 0.875-0.953). Hi-PCS was moderately correlated with pain intensity (r = 0.651) and functional disability (r = 0.352), and negatively correlated with QoL (r = -0.380). CONCLUSIONS : PCS translation and cross-cultural adaptation to Hindi demonstrated good factor structure along adequate psychometric properties and could be recommended for use in CLBP research in India. PMID- 26893112 TI - Effects of a Peer-Led Pain Management Program for Nursing Home Residents with Chronic Pain: A Pilot Study. AB - OBJECTIVES : To examine the feasibility of a peer-led pain management program among nursing home residents. DESIGN : A quasi-experimental design. SETTING : Two nursing homes. SUBJECTS : Fifty nursing home residents. METHODS : The experimental group (n = 32) was given a 12-week group-based peer-led pain management program. There were two 1-hour sessions per week. Education in pain and demonstrations of nonpharmacological pain management strategies were provided. The research team and 12 trained peers led the sessions. The control group (n = 18) received one 1-hour session of pain management program each week over 12 weeks from the research team only. Outcome measures for the participants were collected at baseline (P1) and at week 12 (P2). Data from peer volunteers were collected prior to training (V1) and at week 12 (V2). T-tests were used to compare the differences in outcome measures collected at two time points. RESULTS : There was a significant reduction in pain intensity from 5.8 +/- 2.6 (P1) to 3.4 +/- 2.5 (P2) for the experimental group (p = 0.003) and from 6.3 +/- 3.0 (P1) to 3.1 +/- 2.4 (P2) for the control group (p = 0.001). Activities of daily living significantly improved for both the experimental group (p = 0.008) and the control group (p = 0.014). There was an enhancement in happiness level for the experimental group (p < 0.001), while the loneliness level dropped significantly for the experimental group (p < 0.001) and the control group (p = 0.031). The peer volunteers showed a significant increase in self-rated pain management knowledge (2.9 +/- 2.6 to 8.1 +/- 1.2, p < 0.001) and self-efficacy in volunteering (5.8 +/- 2.9 to 8.3 +/- 1.5, p = 0.032). CONCLUSION : The peer-led pain management program was feasible and has potential in relieving chronic pain and enhancing the physical and psychological health of nursing home residents. PMID- 26893113 TI - Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain. PMID- 26893114 TI - Clinical Efficacy of Percutaneous Endoscopic Lumbar Annuloplasty and Nucleoplasty for Treatment of Patients with Discogenic Low Back Pain. AB - OBJECTIVES: This study assessed the effectiveness of percutaneous endoscopic lumbar annuloplasty and nucleoplasty (PELAN) for the treatment of patients with discogenic low back pain. STUDY DESIGN: Retrospective design SETTING: Spine hospital SUBJECTS: Forty-seven patients diagnosed as having discogenic low back pain, who were refractory to conservative treatments. METHODS: Outcomes were assessed using a numeric rating scale for back pain, the Oswestry disability index, and modified MacNab's criteria, at 2-3 weeks and at least 12 months after treatment. RESULTS: At long-term follow-up, 33 patients (70%) had successful outcomes for relief of pain, and the same proportion had successful reduction of disability. Although all patients took oral analgesics for pain control before PELAN, 25 (53%) required no analgesics at long-term follow-up. If success is defined as simultaneously achieving greater than 50% reduction in pain, greater than 40% reduction of disability, good or excellent MacNab criteria, and no need for analgesics, 23 patients (49%; with 95% confidence interval of 35-63%) achieved successful outcomes. CONCLUSIONS: In patients with discogenic low back pain refractory to conservative treatment, PELAN provided favorable clinical outcomes with success rates that rival those of surgery for this condition. PMID- 26893117 TI - Ganglion Impar Blocks for More Than Coccygodynia. PMID- 26893116 TI - Quantitative Sensory Testing in Chronic Musculoskeletal Pain. AB - BACKGROUND: In recent years, several published articles have demonstrated that quantitative sensory testing (QST) is useful in the analysis of musculoskeletal pain disorders. Based on the evidence from these studies, it is assumed that QST might be a useful tool in the analysis of the pathogenesis, classification, differential diagnosis, and prognosis of chronic musculoskeletal pain. OBJECTIVES: The objective of this paper is to discuss measurement properties of QST and potentials research and clinical applications in musculoskeletal pain. METHODS: This is a review of the current knowledge base on QST as it relates to musculoskeletal pain disorders. We based our summary on articles retrieved from Ovid MEDLINE (1946 to present) including EMBASE, AMED, and PsycINFO databases to search for all published literature focused on QST and musculoskeletal pain. RESULTS: QST has been shown to be related to neural sensitivity in musculoskeletal pain. QST measurement properties have been evaluated for multiple sensory evaluation modalities and protocols with no clear superior instrument or test protocol. The research evidence is incomplete, but suggests potential clinical benefits for predicting outcomes and subtyping pain. Threshold detection testing is commonly used to quantify sensory loss or gain, in current practice and has shown moderate reliability. Intensity/magnitude rating can be assessed on a wide range of rating scales and may be more useful for pain rating in a clinical context. Threshold detection-based testing and intensity/magnitude rating-based testing can be combined to determine pain threshold in clinical evaluation. CONCLUSIONS: Musculoskeletal pain management may benefit from treatment algorithms that consider mechanism, pain quality, or neurophysiological correlates. Non-invasive QST may be helpful to find sensory array of altered nociceptive process. Due to the diverse etiopathogenetic basis of musculoskeletal pain disorders, a broad range of reliable and valid QST tests may be needed to analyze the various disease entities. PMID- 26893118 TI - Pain Modulation and Autonomic Function: The Effect of Clonidine. AB - OBJECTIVE: . The alpha2-agonist clonidine is an analgesic agent, whose yet uncertain action may involve either increase in pain modulation efficiency, change in autonomic function, and/or decrease in anxiety level. The present study aimed to examine the effect of oral clonidine on pain perception in healthy subjects in order to reveal its mode of action. DESIGN: . Randomized, double blind, placebo-controlled study. SUBJECTS: . Forty healthy subjects. METHODS: . Subjects received either 0.15 mg oral clonidine or placebo. We measured pain parameters of heat pain thresholds, tonic heat stimulus, mechanical temporal summation, offset analgesia (OA) and conditioned pain modulation (CPM); autonomic parameters of deep breathing ratio and heart rate variability indices obtained before, during, and after tonic heat stimulus; and psychological parameters of anxiety and pain catastrophizing. RESULTS: . Clonidine decreased systolic blood pressure (P = 0.022) and heart rate (P = 0.004) and increased rMSSD (P = 0.020), though no effect was observed on pain perception, pain modulation, and psychological parameters. Autonomic changes were correlated with pain modulation capacity; for OA, the separate slope model was significant (P = 0.008); in the clonidine group, more efficient OA was associated with lower heart rate (r = 0.633, P = 0.005), unlike in the placebo group. CONCLUSIONS: . The change in autonomic function that was related to the increase in pain modulation capacity, and the lack of change in anxiety, suggest a combined modulatory-autonomic mode of analgesic action for clonidine. PMID- 26893119 TI - Premedication with Intravenous Ibuprofen Improves Recovery Characteristics and Stress Response in Adults Undergoing Laparoscopic Cholecystectomy: A Randomized Controlled Trial. AB - OBJECTIVES: Examine the effect of preoperative dose of IV ibuprofen on stress response and postoperative recovery in laparoscopic cholecystectomy patients. DESIGN: Prospective, randomized, controlled, double-blind, multicenter trial. SETTING: Three university-based, tertiary care hospitals. SUBJECTS: Fifty-five adults, ASA 1, 2, or 3 scheduled for laparoscopic cholecystectomy were given a single preoperative dose of placebo or IV ibuprofen 800 mg. METHODS: Neurobehavioral assessments were evaluated preoperatively, in PACU, POD 1, and POD 3, using the 40-item Quality of Recovery questionnaire (QoR40), 9-item Modified Fatigue Severity Scale (MFSS), and 15-item Geriatric Depression scale (GDS). Blood samples were taken for cytokines (TNF-alpha, IL-1beta, IL-2, IL-6, IL-10, IFNgamma), cortisol, CRP, epinephrine, and norepinephrine prior to the administration of study drug/placebo, intraoperatively, and after surgery. RESULTS: Global QoR40 scores remained at baseline for ibuprofen patients but significantly decreased in the placebo group. Severity of fatigue increased in patients receiving placebo but had no change with ibuprofen. The placebo group had lower GDS scores on POD 3. Epinephrine and norepinephrine were significantly lower intraoperatively for the ibuprofen group. Cortisol decreased postoperatively in the ibuprofen group. There was an impact of drug treatment on the immune response, as seen by an increase in TNFalpha and an increase in IL-10 when compared with placebo. CONCLUSIONS: Our results suggest the addition of NSAIDs may improve the overall quality of recovery, postsurgical fatigue, and early postoperative outcomes. Preoperative administration of IV ibuprofen modulates the stress and inflammatory response, as demonstrated by a decrease in the level of catecholamines, cortisol, and cytokines. TRIAL REGISTRATION: Clinicaltrials.gov identifier: 01938040. PMID- 26893120 TI - Chronic Pain in a Low Socioeconomic Status Population in Singapore: A Cross Sectional Study. AB - PURPOSE: . The authors sought to determine the prevalence of chronic pain in a low socioeconomic-status rental-flat community in Singapore and its associations. In Singapore, >=85% own homes; public rental flats are reserved for the low income. METHODS: . Chronic pain was defined as pain >=3 months. From 2009-2014, residents aged >= 40 years in five public rental-flat enclaves were surveyed for chronic pain, as well as sociodemographic factors. Subsequently, the authors conducted an additional study among elderly (aged >=60) in two public rental-flat enclaves in 2012. The authors compared against residents staying in adjacent owner-occupied public housing. RESULTS: . Prevalence of chronic pain in the rental-flat population was 14.2% (133/936) compared with 14.4% (158/1101) in the owner-occupied population (p = 0.949). On multivariate analysis, among those aged 40-59 years, staying in the rental flat community was independently associated with higher prevalence of leg/ankle/foot pain, compared to staying in the owner occupied flat community (aOR = 2.35, CI = 1.24-7.35, p = 0.008). In the rental flat population, unemployment was associated with chronic pain (aOR = 1.92, 95%, CI = 1.05-2.78, p = 0.030); among the elderly, dependency in instrumental activities-of-daily-living (iADLs) was associated with chronic pain (aOR = 2.38, CI = 1.11-5.00, p = 0.025), as well as female gender, being single, and having higher education (all p > 0.05). CONCLUSIONS: . In this low socioeconomic-status population, chronic pain associated with unemployment and functional limitation. There was no difference in pain prevalence between the rental-flat population and adjacent owner-occupied precincts. PMID- 26893122 TI - Enhancement of dopaminergic activity and region-specific activation of Nrf2-ARE pathway by intranasal supplements of testosterone propionate in aged male rats. AB - The potential influence of intranasal testosterone propionate (InTP) supplements on mesodopaminergic system in aged male rats was investigated by analyzing the exploratory and motor behaviors as well as dopamine neurobiochemical indices. Meanwhile, oxidative stress parameters and pathway of nuclear factor erythroid 2 related factor 2 (Nrf2)-binding antioxidant response elements (Nrf2-ARE) were examined to check whether the Nrf2-ARE pathway was involved in the InTP-induced alteration of mesodopaminergic system in aged male rats. The exploratory and motor behavioral deficits, as well as the reduced expression of dopamine, tyrosine hydroxylase, and dopamine transporter, which indicated the declined activity of mesodopaminergic system, were ameliorated in rats administered with 12-week InTP. The results indicated that chronic InTP supplements could effectively influence the brain function activity in a way opposite to the effect of aging on the mesodopaminergic system of rats. The increased levels of Nrf2, heme oxygenase-1, and NAD(P)H: quinone oxidoreductase-1 in the substantia nigra and ventral tegmental area, but not in the hippocampus of InTP-administered aged male rats, indicated that the ameliorative effect of InTP supplements on mesodopaminergic system might be related to the region-specific activation of the Nrf2-ARE pathway. PMID- 26893121 TI - Variation in the Oxytocin Receptor Gene Predicts Brain Region-Specific Expression and Social Attachment. AB - BACKGROUND: Oxytocin (OXT) modulates several aspects of social behavior. Intranasal OXT is a leading candidate for treating social deficits in patients with autism spectrum disorder, and common genetic variants in the human OXTR gene are associated with emotion recognition, relationship quality, and autism spectrum disorder. Animal models have revealed that individual differences in Oxtr expression in the brain drive social behavior variation. Our understanding of how genetic variation contributes to brain OXTR expression is very limited. METHODS: We investigated Oxtr expression in monogamous prairie voles, which have a well-characterized OXT system. We quantified brain region-specific levels of Oxtr messenger RNA and oxytocin receptor protein with established neuroanatomic methods. We used pyrosequencing to investigate allelic imbalance of Oxtr mRNA, a molecular signature of polymorphic genetic regulatory elements. We performed next generation sequencing to discover variants in and near the Oxtr gene. We investigated social attachment using the partner preference test. RESULTS: Our allelic imbalance data demonstrate that genetic variants contribute to individual differences in Oxtr expression, but only in particular brain regions, including the nucleus accumbens, where oxytocin receptor signaling facilitates social attachment. Next-generation sequencing identified one polymorphism in the Oxtr intron, near a putative cis-regulatory element, explaining 74% of the variance in striatal Oxtr expression specifically. Males homozygous for the high expressing allele display enhanced social attachment. CONCLUSIONS: Taken together, these findings provide convincing evidence for robust genetic influence on Oxtr expression and provide novel insights into how noncoding polymorphisms in OXTR might influence individual differences in human social cognition and behavior. PMID- 26893124 TI - Synthesis of quaternary alpha-perfluoroalkyl lactams via electrophilic perfluoroalkylation. AB - Efficient protocols enabling the rapid installation of trifluoromethyl, as well as further functionalized fluoroalkyl groups by an electrophilic perfluoroalkylation of lactam-derived ketene silyl amides (KSAs) using hypervalent iodine reagents 1 and 2 have been developed. PMID- 26893125 TI - Exploring the information needs of people living with a long-term indwelling urinary catheter: a qualitative study. AB - AIMS: To explore the information needs of long-term indwelling urinary catheter users, the consequences for patients of inadequate information and how these needs could be met. BACKGROUND: Previous studies have drawn attention to the lack of information given to indwelling catheter users and how users would benefit from more. Little is known about the varied and detailed information needs of long-term indwelling catheter users. DESIGN: A qualitative interpretative approach was used, combining thematic analysis with constant comparison. A diverse sample of people living in the community with a catheter for 3 months or longer was recruited. METHODS: Interviews were conducted using a narrative approach. Thirty-six interviews were conducted in England, Wales and Scotland between 2011-2013. RESULTS: Participants ranged in age from 22-96 years. After having a catheter fitted they wanted more technical information about it and information to help prevent catheter-related physical problems (infection, blockage, leaking), on sexual activity and the siting of catheters and about managing a social life with a catheter. In its absence, patients sometimes experimented with the catheter, learning to live with it through trial and error, used the Internet to find out more, or contacted other patients or organizations. CONCLUSION: Research has consistently shown that indwelling catheter users need to be given more information but some patients still feel poorly informed. Nurses are in a good position to find out what people know, what they need, and to ensure that patients have contact phone numbers for further information and details of reliable websites and support organizations. PMID- 26893123 TI - Transcriptome comparisons shed light on the pre-condition and potential barrier for C4 photosynthesis evolution in eudicots. AB - C4 photosynthesis evolved independently from C3 photosynthesis in more than 60 lineages. Most of the C4 lineages are clustered together in the order Poales and the order Caryophyllales while many other angiosperm orders do not have C4 species, suggesting the existence of biological pre-conditions in the ancestral C3 species that facilitate the evolution of C4 photosynthesis in these lineages. To explore pre-adaptations for C4 photosynthesis evolution, we classified C4 lineages into the C4-poor and the C4-rich groups based on the percentage of C4 species in different genera and conducted a comprehensive comparison on the transcriptomic changes between the non-C4 species from the C4-poor and the C4 rich groups. Results show that species in the C4-rich group showed higher expression of genes related to oxidoreductase activity, light reaction components, terpene synthesis, secondary cell synthesis, C4 cycle related genes and genes related to nucleotide metabolism and senescence. In contrast, C4-poor group showed up-regulation of a PEP/Pi translocator, genes related to signaling pathway, stress response, defense response and plant hormone metabolism (ethylene and brassinosteroid). The implications of these transcriptomic differences between the C4-rich and C4-poor groups to C4 evolution are discussed. PMID- 26893126 TI - Justifications for coercive care in child and adolescent psychiatry, a content analysis of medical documentation in Sweden. AB - BACKGROUND: There has been considerable interest in normative ethics regarding how and when coercive care can be justified. However, only a few empirical studies consider how professionals reason about ethical aspects when assessing the need for coercive care for adults, and even less concerning children and adolescents. The aim of this study was to examine and describe how professionals document their value arguments when considering the need for coercive psychiatric care of young people. METHODS: All 16 clinics that admitted children or adolescents to coercive care during one year in Sweden were included in the study. These clinics had a total of 155 admissions of 142 patients over one year. Qualitative content analysis with a deductive approach was used to find different forms of justification for coercive care that was documented in the medical records, including Care Certificates. RESULTS: The analysis of medical records revealed two main arguments used to justify coercive care in child and adolescent psychiatry: 1) the protection argument - the patients needed protection, mainly from themselves, and 2) the treatment requirement argument - coercive care was a necessary measure for administering treatment to the patient. Other arguments, namely the caregiver support argument, the clarification argument and the solidarity argument, were used primarily to support the two main arguments. These supportive arguments were mostly used when describing the current situation, not in the explicit argumentation for coercive care. The need for treatment was often only implicitly clarified and the type of care the patient needed was not specified. Few value arguments were used in the decision for coercive care; instead physicians often used their authority to convince others that treatment was necessary. CONCLUSIONS: One clinical implication of the study is that decisions about the use of coercive care should have a much stronger emphasis on ethical aspects. There is a need for an ethical legitimacy founded upon explicit ethical reasoning and after communication with the patient and family, which should be documented together with the decision to use coercive care. PMID- 26893129 TI - The wounded blogger: analysis of narratives by women with breast cancer. AB - The purpose of this article is to analyse the representation of the body in seven blogs by Spanish women with breast cancer. Using both texts and images, we analyse how they reproduce modern and postmodern logic to represent the wounded body. Based on Frank's proposals, this article draws the conclusion that the women bloggers mainly reproduce the modern logic (characterised by the restitution narrative and a predictable, disassociated and monadic body), but there are elements which break with this logic (the quest narrative, the body presented as associated, dyadic and full of desire, and the acceptance of contingency). After applying Frank's categories, we suggest that the contemporary way of experiencing illness may question the clarity of the modern/postmodern divide. PMID- 26893128 TI - Go!: results from a quasi-experimental obesity prevention trial with hospital employees. AB - BACKGROUND: Worksite obesity prevention interventions using an ecological approach may hold promise for reducing typical weight gain. The purpose of this study was to examine the effectiveness of Go!, an innovative 12-month multi component worksite obesity prevention intervention. METHODS: A quasi-experimental non-equivalent control group design was utilized; 407 eligible hospital employees (intervention arm) and 93 eligible clinic employees (comparison arm) participated. The intervention involved pedometer distribution, labeling of all foods in the worksite cafeteria and vending machines (with calories, step equivalent, and a traffic light based on energy density signaling recommended portion), persuasive messaging throughout the hospital, and the integration of influential employees to reinforce healthy social norms. Changes in weight, BMI, waist circumference, physical activity, and dietary behavior after 6 months and 1 year were primary outcomes. Secondary outcomes included knowledge, perceptions of employer commitment to employee health, availability of information about diet, exercise, and weight loss, perceptions of coworker support and frequency of health discussions with coworkers. A process evaluation was conducted as part of the study. RESULTS: Repeated measures ANCOVA indicated that neither group showed significant increases in weight, BMI, or waist circumference over 12 months. The intervention group showed a modest increase in physical activity in the form of walking, but decreases in fruit and vegetable servings and fiber intake. They also reported significant increases in knowledge, information, perceptions of employer commitment, and health discussions with peers. Employees expressed positive attitudes towards all components of the Go! CONCLUSIONS: This low intensity intervention was well-received by employees but had little effect on their weight over the course of 12 months. Such results are consistent with other worksite obesity prevention studies using ecological approaches. Implementing low impact physical activity (e.g., walking, stair use) may be more readily incorporated into the worksite setting than more challenging behaviors of altering dietary habits and increasing more vigorous forms of physical activity. TRIAL REGISTRATION: This study was registered with clinicaltrials.gov (NCT01585480) on April 24, 2012. PMID- 26893127 TI - Should compulsive sexual behavior be considered an addiction? AB - AIMS: To review the evidence base for classifying compulsive sexual behavior (CSB) as a non-substance or 'behavioral' addiction. METHODS: Data from multiple domains (e.g. epidemiological, phenomenological, clinical, biological) are reviewed and considered with respect to data from substance and gambling addictions. RESULTS: Overlapping features exist between CSB and substance use disorders. Common neurotransmitter systems may contribute to CSB and substance use disorders, and recent neuroimaging studies highlight similarities relating to craving and attentional biases. Similar pharmacological and psychotherapeutic treatments may be applicable to CSB and substance addictions, although considerable gaps in knowledge currently exist. CONCLUSIONS: Despite the growing body of research linking compulsive sexual behavior (CSB) to substance addictions, significant gaps in understanding continue to complicate classification of CSB as an addiction. PMID- 26893130 TI - Gold/diamond nanohybrids may reveal how hyperlocalized hyperthermia kills cancer cells. PMID- 26893131 TI - Agarol, an ergosterol derivative from Agaricus blazei, induces caspase independent apoptosis in human cancer cells. AB - Agaricus blazei (A. blazei) is a mushroom with many biological effects and active ingredients. We purified a tumoricidal substance from A. blazei, an ergosterol derivative, and named it 'Agarol'. Cytotoxic effects of Agarol were determined by the MTT assay using A549, MKN45, HSC-3, and HSC-4 human carcinoma cell lines treated with Agarol. Apoptosis was detected by flow cytometry analysis. Reactive oxygen species (ROS) levels and mitochondria membrane potential (?psim) were also determined by flow cytometry. Western blot analysis was used to quantify the expression of apoptosis-related proteins. Agarol predominantly induced apoptosis in two p53-wild cell lines (A549 and MKN45) compared to the other p53-mutant cell lines (HSC-3 and HSC-4). Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of ROS, reduced ?psim, release of apoptosis-inducing factor (AIF) from the mitochondria to the cytosol, upregulation of Bax, and downregulation of Bcl-2. Caspase-3 activities did not increase, and z-VAD-fmk, a caspase inhibitor, did not inhibit the Agarol-induced apoptosis. These findings indicate that Agarol induces caspase-independent apoptosis in human carcinoma cells through a mitochondrial pathway. The in vivo anticancer activity of Agarol was confirmed in a xenograft murine model. This study suggests a molecular mechanism by which Agarol induces apoptosis in human carcinoma cells and indicates the potential use of Agarol as an anticancer agent. PMID- 26893132 TI - Telephone triage in general practices: A written case scenario study in the Netherlands. AB - OBJECTIVE: General practices increasingly use telephone triage to manage patient flows. During triage, the urgency of the call and required type of care are determined. This study examined the organization and adequacy of telephone triage in general practices in the Netherlands. DESIGN: Cross-sectional observational study using a web-based survey among practice assistants including questions on background characteristics and triage organization. Furthermore, practice assistants were asked to assess the required type of care of written case scenarios with varying health problems and levels of urgency. To determine the adequacy of the assessments, a comparison with a reference standard was made. In addition, the association between background characteristics and triage organization and the adequacy of triage was examined. SETTING: Daytime general practices. SUBJECTS: Practice assistants. MAIN OUTCOME MEASURES: Over- and under estimation, sensitivity, specificity. RESULTS: The response rate was 41.1% (n = 973). The required care was assessed adequately in 63.6% of cases, was over estimated in 19.3%, and under-estimated in 17.1%. The sensitivity of identifying patients with a highly urgent problem was 76.7% and the specificity was 94.0%. The adequacy of the assessments of the required care was higher for more experienced assistants and assistants with fixed daily work meetings with the GP. Triage training, use of a triage tool, and authorization of advice were not associated with adequacy of triage. CONCLUSION: Triage by practice assistants in general practices is efficient (high specificity), but potentially unsafe in highly urgent cases (suboptimal sensitivity). It is important to train practice assistants in identifying highly urgent cases. KEY POINTS: General practices increasingly use telephone triage to manage patient flows, but little is known about the organization and adequacy of triage in daytime practices. Telephone triage by general practice assistants is efficient, but potentially unsafe in highly urgent cases. The adequacy of triage is higher for more experienced assistants and assistants with fixed daily work meetings with the general practitioner. PMID- 26893134 TI - Communication of Recurrence Risk Estimates to Patients Diagnosed With Breast Cancer. PMID- 26893136 TI - [The future of radiology: What can we expect within the next 10 years?]. AB - More than other medical discipline, radiology is marked by technical innovation and continuous development, as well as the optimization of the underlying physical principles. In this respect, several trends that will crucially change and develop radiology over the next decade can be observed. Through the use of ever faster computer tomography, which also shows an ever-decreasing radiation exposure, the "workhorse" of radiology will have an even greater place and displace conventional X-ray techniques further. In addition, hybrid imaging, which is based on a combination of nuclear medicine and radiological techniques (keywords: PET/CT, PET/MRI) will become much more established and, in particular, will improve oncological imaging further, allowing increasingly individualized imaging for specific tracers and techniques of functional magnetic resonance imaging for a particular tumour. Future radiology will be strongly characterized by innovations in the software and Internet industry, which will enable new image viewing and processing methods and open up new possibilities in the context of the organization of radiological work. PMID- 26893133 TI - Metabolism of murine TH 17 cells: Impact on cell fate and function. AB - An effective adaptive immune response relies on the ability of lymphocytes to rapidly act upon a variety of insults. In T lymphocytes, this response includes cell growth, clonal expansion, differentiation, and cytokine production, all of which place a significant energy burden on the cell. Recent evidence shows that T cell metabolic reprogramming is an essential component of the adaptive immune response and specific metabolic pathways dictate T-cell fate decisions, including the development of TH 17 versus T regulatory (Treg) cells. TH 17 cells have garnered significant attention due to their roles in the pathology of immune mediated inflammatory diseases. Attempts to characterize TH 17 cells have demonstrated that they are highly dynamic, adjusting their function to environmental cues, which dictate their metabolic program. In this review, we highlight recent data demonstrating the impact of cellular metabolism on the TH 17/Treg balance and present factors that mediate TH 17-cell metabolism. Some examples of these include the differential impact of the mTOR signaling complexes on T-helper-cell differentiation, hypoxia inducible factor 1 alpha (HIF1alpha) promotion of glycolysis to favor TH 17-cell development, and ACC1-dependent de novo fatty acid synthesis favoring TH 17-cell development over Treg cells. Finally, we discuss the potential therapeutic options and the implications of modulating TH 17-cell metabolism for the treatment of TH 17-mediated diseases. PMID- 26893135 TI - Evaluation of Pharmacists' Work in a Physician-Pharmacist Collaborative Model for the Management of Hypertension. AB - STUDY OBJECTIVE: Physician-pharmacist collaborative models have been shown to improve the care of patients with numerous chronic medical conditions. Team-based health care using integrated clinical pharmacists provides one opportunity to improve quality in health care systems that use population-based financing. In November 2015, the Centers for Medicare and Medicaid Services (CMS) requested that the relative value of pharmacists' work in team-based care needs to be established. Thus the objective of this study was to describe the components of pharmacists' work in the management of hypertension with a physician-pharmacist collaborative model. DESIGN: Descriptive analysis of the components of pharmacists' work in the Collaboration Among Pharmacists and Physicians to Improve Outcomes Now (CAPTION) study, a prospective, cluster randomized trial. MEASUREMENTS AND MAIN RESULTS: This analysis was intended to provide policymakers with data and information, using the CAPTION study model, on the time and intensity of pharmacists' work to understand pharmacists' relative value contributions in the context of CMS financing and population management aims. The CAPTION trial was conducted in 32 community-based medical offices in 15 U.S. states and included 390 patients with multiple cardiovascular risk factors. Blood pressure was measured by trained study coordinators in each office, and patients were included in the study if they had uncontrolled blood pressure. Included patients were randomized to a 9-month intervention, a 24-month intervention, or usual care. The goal of the pharmacist intervention was to improve blood pressure control and resolve drug therapy problems impeding progress toward blood pressure goals. This intervention included medical record review, a structured assessment with the patient, collaboration to achieve goals of therapy, and patient follow up. The two intervention arms (9 and 24 mo) were identical the first 9 months, and that time frame is the focus of this workload evaluation. Pharmacists completed study encounter forms for every patient encounter and estimated time spent in pre-visit, face-to-face care, and post-visit activities. Among the 390 patients, there were 2811 encounters with pharmacists that involved 3.44 hours/patient for face-to-face care visits plus 1.55 hours/patient for pre-visit and post-visit work. Intensity of work was reflected in interventions to resolve drug therapy problems with patients (43% of encounters) and with physicians (1169 recommendations, of which physicians accepted 1153 [98.6%]), resulting in improvement of patients' blood pressure goals achieved (from 0% at baseline to 43% at 9 months based on the primary study end point). CONCLUSION: Pharmacists provided extensive interventions to patients with hypertension. This analysis provides a framework for health systems, provider groups, and payers to measure pharmacists' work in value-based financing and population management. PMID- 26893137 TI - [Radiotherapy in node-positive prostate cancer]. AB - BACKGROUND: There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. OBJECTIVES: This overview summarizes the existing literature on the use of radiotherapy for node positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. RESULTS: The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with <= 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. CONCLUSION: There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer. PMID- 26893138 TI - Physical activity and its correlates in children and adolescents post-liver transplant. AB - The health benefits of PA are well established for healthy and chronically ill children. This study objectively measures physical fitness and PA levels in children PLT and explores potential correlates and perceived barriers impacting their PA. A total of 23 children (16 females, mean 14.01 +/- 2.49 yrs) >1 yr PLT were assessed for peak oxygen consumption (VO2 peak), muscle strength, endurance, and flexibility. MVPA and steps/day were determined with accelerometry. Additionally, SE, perceived fatigue, and barriers and benefits of PA were examined. VO2 peak (mean 33. 2 +/- 7.61 mL/kg/min; 77.0 +/- 15.6% predicted) and PA (average 6841 +/- 2299 steps/day) were below healthy norms. MVPA (31.6 +/- 16.1 min/day) was lower than national guidelines. Six participants (30%) attained criterion standards for abdominal strength and one participant (5%) for push-ups. Fatigue and SE were lower than reported levels in healthy children. A commonly perceived barrier to PA was "I am tired." A positive correlation was shown between SE and MVPA (r = 0.57, p = 0.007), SE and fatigue (r = 0.54, p = 0.01), and PELD score and fatigue (r = 0.66, p = 0.007). Children PLT demonstrate below normal levels of PA and aerobic capacity. SE is a modifiable correlate of their PA. Further investigation of the impact of PA correlates can guide the development of future innovative PA intervention strategies in children PLT. PMID- 26893140 TI - Estimation of Radiation Dose in CT Based on Projection Data. AB - Managing and optimizing radiation dose has become a core problem for the CT community. As a fundamental step for dose optimization, accurate and computationally efficient dose estimates are crucial. The purpose of this study was to devise a computationally efficient projection-based dose metric. The absorbed energy and object mass were individually modeled using the projection data. The absorbed energy was estimated using the difference between intensity of the primary photon and the exit photon. The mass was estimated using the volume under the attenuation profile. The feasibility of the approach was evaluated across phantoms with a broad size range, various kVp settings, and two bowtie filters, using a simulation tool, the Computer Assisted Tomography SIMulator (CATSIM) software. The accuracy of projection-based dose estimation was validated against Monte Carlo (MC) simulations. The relationship between projection-based dose metric and MC dose estimate was evaluated using regression models. The projection-based dose metric showed a strong correlation with Monte Carlo dose estimates (R (2) > 0.94). The prediction errors for the projection-based dose metric were all below 15 %. This study demonstrated the feasibility of computationally efficient dose estimation requiring only the projection data. PMID- 26893141 TI - Commentary to: Effect of continuous ozone injection on performance and biomass accumulation of biofilters treating gaseous toluene. PMID- 26893142 TI - Deammonification for digester supernatant pretreated with thermal hydrolysis: overcoming inhibition through process optimization. AB - The thermal hydrolysis process (THP) has been proven to be an excellent pretreatment step for an anaerobic digester (AD), increasing biogas yield and decreasing sludge disposal. The goal of this work was to optimize deammonification for efficient nitrogen removal despite the inhibition effects caused by the organics present in the THP-AD sludge filtrate (digestate). Two sequencing batch reactors were studied treating conventional digestate and THP-AD digestate, respectively. Improved process control based on higher dissolved oxygen set-point (1 mg O2/L) and longer aeration times could achieve successful treatment of THP-AD digestate. This increased set-point could overcome the inhibition effect on aerobic ammonium-oxidizing bacteria (AerAOB), potentially caused by particulate and colloidal organics. Moreover, based on the mass balance, anoxic ammonium-oxidizing bacteria (AnAOB) contribution to the total nitrogen removal decreased from 97 +/- 1 % for conventional to 72 +/- 5 % for THP AD digestate treatment, but remained stable by selective AnAOB retention using a vibrating screen. Overall, similar total nitrogen removal rates of 520 +/- 28 mg N/L/day at a loading rate of 600 mg N/L/day were achieved in the THP-AD reactor compared to the conventional digestate treatment operating at low dissolved oxygen (DO) (0.38 +/- 0.10 mg O2/L). PMID- 26893139 TI - An external sensing system in Plasmodium falciparum-infected erythrocytes. AB - BACKGROUND: A number of experiments have previously indicated that Plasmodium falciparum-infected erythrocytes (pRBC) were able to sense host environment. The basis of this ability to detect external cues is not known but in screening signalling molecules from pRBC using commercial antibodies, a 34 kDa phosphorylated molecule that possesses such ability was identified. METHODS: The pRBC were exposed to different culture conditions and proteins were extracted for 1D or 2D gel electrophoresis followed by Western blot. The localization of 34 kDa protein was examined by biochemical fractionation followed by Western blot. High resolution mass spectrometric analysis of immune precipitants was used to identify this protein and real-time quantitative reverse transcriptase polymerase chain reaction was used for detecting mRNA expression level. RESULTS: The 34 kDa protein was called PfAB4 has immediate responses (dephosphorylation and rapid turnover) to host environmental stimuli such as serum depletion, osmolality change and cytokine addition. PfAB4 is expressed constitutively throughout the erythrocytic lifecycle with dominant expression in trophozoites 30 h post infection. Tumour necrosis factor (TNF) treatment induced a transient detectable dephosphorylation of PfAB4 in the ItG strain (2 min after addition) and the level of expression and phosphorylation returned to normal within 1-2 h. PfAB4 localized dominantly in pRBC cytoplasm, with a transient shift to the nucleus under TNF stimulation as shown by biochemical fractionation. High-resolution mass spectrometric analysis of immune precipitants of AB4 antibodies revealed a 34 kDa PfAB4 component as a mixture of proliferating cellular nuclear antigen-1 (PCNA1) and exported protein-2 (EXP2), along with a small number of other inconsistently identified peptides. Different parasite strains have different PfAB4 expression levels, but no significant association between mRNA and PfAB4 levels was seen, indicating that the differences may be at the post-transcriptional, presumably phosphorylation, level. A triple serine phosphorylated PCNA1 peptide was identified from the PfAB4 high expression strain only, providing further evidence that the identity of PfAB4 is PCNA1 in P. falciparum. CONCLUSION: A protein element in the human malaria parasite that responds to external cues, including the pro-inflammatory cytokine TNF have been discovered. Treatment results in a transient change in phosphorylation status of the response element, which also migrates from the parasite cytoplasm to the nucleus. The response element has been identified as PfPCNA1. This sensing response could be regulated by a parasite checkpoint system and be analogous to bacterial two-component signal transduction systems. PMID- 26893145 TI - Overexpression of SIRT3 disrupts mitochondrial proteostasis and cell cycle progression. PMID- 26893146 TI - Structural characterization, phase transition and switchable dielectric behaviors in a new zigzag chain organic-inorganic hybrid compound: [C3H7NH3]2SbI5. AB - A novel zigzag chain organic-inorganic hybrid compound of the general formula R2MI5, [n-C3H7NH3]2[SbI5] (1), was successfully synthesized, in which the n propylammonium cations were located in the free cavities between the one dimensional zigzag chains. Systematic characterization was performed to investigate the phase transition of 1. A pair of sharp peaks at 211.8 K (heating) and 203.7 K (cooling) with a hysteresis 8.1 K were observed in the differential scanning calorimetry (DSC) curve, indicating the first-order phase transition behavior of 1. The temperature dependence dielectric measurement demonstrated a step-like change at around 211.8 K, which makes 1 a potential switchable dielectric material. Frequency dependence measurement revealed that the frequency exerts a weak influence on the dielectric permittivity. Further structural analysis shows that both anionic and cationic moieties contribute to the phase transition, accompanied by weak hydrogen bond interactions between cations and the [SbI5]n(2-) chains. PMID- 26893143 TI - Suicide Gene-Engineered Stromal Cells Reveal a Dynamic Regulation of Cancer Metastasis. AB - Cancer-associated fibroblasts (CAFs) are a major cancer-promoting component in the tumor microenvironment (TME). The dynamic role of human CAFs in cancer progression has been ill-defined because human CAFs lack a unique marker needed for a cell-specific, promoter-driven knockout model. Here, we developed an engineered human CAF cell line with an inducible suicide gene to enable selective in vivo elimination of human CAFs at different stages of xenograft tumor development, effectively circumventing the challenge of targeting a cell-specific marker. Suicide-engineered CAFs were highly sensitive to apoptosis induction in vitro and in vivo by the addition of a simple small molecule inducer. Selection of timepoints for targeted CAF apoptosis in vivo during the progression of a human breast cancer xenograft model was guided by a bi-phasic host cytokine response that peaked at early timepoints after tumor implantation. Remarkably, we observed that the selective apoptosis of CAFs at these early timepoints did not affect primary tumor growth, but instead increased the presence of tumor associated macrophages and the metastatic spread of breast cancer cells to the lung and bone. The study revealed a dynamic relationship between CAFs and cancer metastasis that has counter-intuitive ramifications for CAF-targeted therapy. PMID- 26893148 TI - Medical maternalism: beyond paternalism and antipaternalism. AB - This paper argues that the concept of paternalism is currently overextended to include a variety of actions that, while resembling paternalistic actions, are importantly different. I use the example of Japanese physicians' non-disclosures of cancer diagnoses directly to patients, arguing that the concept of maternalism better captures these actions. To act paternalistically is to substitute one's own judgement for that of another person and decide in place of that person for his/her best interest. By contrast, to act maternalistically is to decide for another person based on a reasonable understanding of that person's own preferences. The concept of maternalism allows for a more thorough assessment of the moral justification of these types of actions. I conclude that it is possible, at least in principle, to justify Japanese physicians' non-disclosures, and that this justification must be based on an understanding of these actions as maternalistic. PMID- 26893144 TI - Leukocyte populations and IL-6 in the tumor microenvironment of an orthotopic colorectal cancer model. AB - Colorectal cancer (CRC) is a major health problem worldwide. It is often diagnosed late due to its asymptomatic nature. As with all cancers, an immune reaction is involved; however, in CRC, it is unknown if this immune response is favorable or unfavorable for disease progression. In this study, the immune response in mesenteric lymph nodes (MLNs) and Peyer's patches was investigated during development of CRC in an orthotopic mouse model. CRC was induced by injecting CT26 cells into the cecum wall of BALB/c mice. Flow cytometry was used to analyze leukocyte populations involved in tumor immunity in MLNs and Peyer's patches. Cryostat sections for immunohistochemistry were prepared from the caecum and colon from CRC-induced and sham-operated animals. Cytokines produced by mouse CT26 cell line were measuredin vitroandin vivo Significant increases in the number of CD8(+)/TCR(+)and CD49b(+)/TCR(-)(natural killer) cells were found in MLNs and Peyer's patches in the CRC group. In addition, gammadeltaT cells were present in the lamina propria of the colon tissues from sham-operated mice, but absent in the colon tissues from mice with CRC. Immunohistochemical analysis of tumorous tissues showed eosinophil, CD69(+)T cell, and CD11b(+)cell infiltration. Bothin vitroandin vivoCT26 tumor cells were interleukin (IL)-6 positive. In addition, tumor-infiltrating CD45(+)cells were also IL-6 positive. In summary, the kinetics of the immune response to CRC and the key effector lymphocytes that are implicated in tumor immunity are demonstrated. Furthermore, IL-6 is a key cytokine present within the tumor microenvironment. PMID- 26893149 TI - "Protein" Measurement in Biological Wastewater Treatment Systems: A Critical Evaluation. AB - Five commercially available assay kits were tested on the same protein sample with the addition of 17 different types of interfering substances typically found in the biological wastewater treatment, and a comparison of the use of these assays with 22 different protein and peptide samples is also presented. It was shown that a wide variety of substances can interfere dramatically with these assays; the metachromatic response was also clearly influenced by different proteinaceous material. Measurement of the "protein" content in the effluent of an anaerobic membrane bioreactor was then carried out using these assay methods. Quantitative results of the "protein" concentration in the different effluent samples, with or without spiked additions of Bovine Serum Albumin (BSA), showed considerable disagreement. We concluded that the "protein" measured in wastewater samples using standard colorimetric assays often shows false positive results and has little correlation to their real value. A new analytical method needs to be developed in order to gain greater insight into the biological transformations occurring in anaerobic digestion, and how soluble microbial products (SMPs) are produced. PMID- 26893147 TI - Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells. AB - Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFbeta signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications. PMID- 26893150 TI - What Pediatricians and Other Clinicians Should Know About Zika Virus. PMID- 26893152 TI - Switchable-Hydrophilicity Solvents for Product Isolation and Catalyst Recycling in Organocatalysis. AB - Switchable-hydrophilicity solvents (SHSs) are solvents that can switch reversibly between a water-miscible state to a state that forms a biphasic mixture with water. In this case study, SHSs have been studied for easy product/catalyst separation as well as catalyst recycling. A series of tertiary amine SHSs have been identified for the extraction of the hydrophilic product from the postreaction mixture. Here, we determined high extraction efficiencies for the product (>84%) and low extraction rates for the catalyst (<0.1%). With the catalyst recycling experiments, we isolated the product in high purity (>98%) without further purification steps. At the same time, the catalyst was reused without any loss of activity (>91% enantiomeric excess, >99% yield) four times. Furthermore, we optimized the extraction efficiency by working with a microextractor. In addition, with the use of a falling-film microreactor, we obtained the product with high enantioselectivity by working at ambient conditions. PMID- 26893151 TI - Epicrania Fugax. AB - Epicrania fugax (EF) is a primary headache of recent description. EF essentially consists of brief paroxysms of pain describing a linear or zigzag trajectory across the surface of one hemicranium, commencing and terminating in the territories of different nerves. The pain of forward EF originates in a particular area of the occipital, parietal or temporal regions and moves anteriorly, whereas the pain of backward EF originates in the frontal area, the eye or the nose and moves posteriorly. Some patients have ocular or nasal autonomic accompaniments, and some have triggers. Between attacks, many patients have continuous or intermittent pain and/or tenderness at the stemming area. Pain frequency is extremely variable and some patients have spontaneous remissions. Preventive therapy is required when the paroxysms are frequent and non-remitting. Neuromodulators, indomethacin, amitryptiline, nerve anesthetic blockades, and trochlear steroid injections have been used in different cases, with partial or complete response. PMID- 26893153 TI - Ultraviolet-C light effect on physicochemical, bioactive, microbiological, and sensorial characteristics of carrot (Daucus carota) beverages. AB - The aim of this research was to evaluate the effect of ultraviolet-C light on physicochemical, bioactive, microbial, and sensory characteristics of carrot beverages. Beverages were formulated with different concentrations of carrot juice (60, 80, and 100% [v/v]) and treated with ultraviolet-C light at different flow rates (0, 0.5, 3.9, and 7.9 mL s(-1)) and times (5, 10, 15, 20, and 30 min), equivalent to ultraviolet-C dosages of 13.2, 26.4, 39.6, 52.8, and 79.2 J cm(-2) Total soluble solids, pH, and titratable acidity were not affected by the ultraviolet-C light treatment. Ultraviolet-C light significantly affected (p < 0.05) color parameters of pure juice; however, at low concentration of juice, total color change was slightly affected (DeltaE = 2.0 +/- 0.7). Phenolic compounds (4.1 +/- 0.1, 5.2 +/- 0.2, and 8.6 +/- 0.3 mg of GAE 100 mL(-1) of beverage with 60, 80, and 100% of juice, respectively) and antioxidant capacity (6.1 +/- 0.4, 8.5 +/- 0.4, and 9.4 +/- 0.3 mg of Trolox 100 mL(-1) of beverage with 60, 80, and 100% of juice, respectively) of carrot beverages were not affected by ultraviolet-C light treatment. Microbial kinetics showed that mesophiles were mostly reduced at high flow rates in carrot beverages with 60% of juice. Maximum logarithmic reductions for mesophiles and total coliforms were 3.2 +/- 0.1 and 2.6 +/- 0.1, respectively, after 30 min of ultraviolet-C light processing. Beverages were well accepted (6-7) by judges who did not perceive the difference between untreated and Ultraviolet-C light treated beverages. PMID- 26893154 TI - Cell type of origin influences iPSC generation and differentiation to cells of the hematoendothelial lineage. AB - The use of induced pluripotent stem cells (iPSCs) as a source of cells for cell based therapy in regenerative medicine is hampered by the limited efficiency and safety of the reprogramming procedure and the low efficiency of iPSC differentiation to specialized cell types. Evidence suggests that iPSCs retain an epigenetic memory of their parental cells with a possible influence on their differentiation capacity in vitro. We reprogramme three cell types, namely human umbilical cord vein endothelial cells (HUVECs), endothelial progenitor cells (EPCs) and human dermal fibroblasts (HDFs), to iPSCs and compare their hematoendothelial differentiation capacity. HUVECs and EPCs were at least two fold more efficient in iPSC reprogramming than HDFs. Both HUVEC- and EPC-derived iPSCs exhibited high potentiality toward endothelial cell differentiation compared with HDF-derived iPSCs. However, only HUVEC-derived iPSCs showed efficient differentiation to hematopoietic stem/progenitor cells. Examination of DNA methylation at promoters of hematopoietic and endothelial genes revealed evidence for the existence of epigenetic memory at the endothelial genes but not the hematopoietic genes in iPSCs derived from HUVECs and EPCs indicating that epigenetic memory involves an endothelial differentiation bias. Our findings suggest that endothelial cells and EPCs are better sources for iPSC derivation regarding their reprogramming efficiency and that the somatic cell type used for iPSC generation toward specific cell lineage differentiation is of importance. PMID- 26893155 TI - Substantia nigra hyperechogenicity and Parkinson's disease risk in patients with essential tremor. AB - BACKGROUND: Several studies have reported an increased risk for patients with essential tremor to develop Parkinson's disease. In addition, hyperechogenicity in the area of the substantia nigra has been associated with a markedly increased risk for Parkinson's disease. The objective of this study was to evaluate the validity of substantia nigra hyperechogenicity in patients with essential tremor as a risk marker for Parkinson's disease. METHODS: Transcranial sonography was performed in 70 patients suffering from essential tremor. Fifty-four of these patients were available for follow-up after a mean of 6.16 +/- 2.05 years and were assessed for the incidence of new-onset Parkinson's disease. RESULTS: The relative risk for developing Parkinson's disease in patients with essential tremor who had hyperechogenicity at baseline versus those without this hyperechogenicity was 7.00 (95% confidence interval, 1.62-30.34; sensitivity, 77.8%; specificity, 75.6%). CONCLUSIONS: Substantia nigra hyperechogenicity is also associated with an increased risk for Parkinson's disease in patients with essential tremor. These findings further support the potential role of this echofeature as a risk marker for Parkinson's disease. PMID- 26893156 TI - Protection from experimental autoimmune encephalomyelitis by polyclonal IgG requires adjuvant-induced inflammation. AB - BACKGROUND: Intravenous immunoglobulin (IVIG) proved to be an efficient anti inflammatory treatment for a growing number of neuroinflammatory diseases and protects against the development of experimental autoimmune encephalomyelitis (EAE), a widely used animal model for multiple sclerosis (MS). METHODS: The clinical efficacy of IVIG and IVIG-derived F(ab')2 fragments, generated using the streptococcal cysteine proteinase Ide-S, was evaluated in EAE induced by active immunization and by adoptive transfer of myelin-specific T cells. Frequency, phenotype, and functional characteristics of T cell subsets and myeloid cells were determined by flow cytometry. Antibody binding to microbial antigen and cytokine production by innate immune cells was assessed by ELISA. RESULTS: We report that the protective effect of IVIG is lost in the adoptive transfer model of EAE and requires prophylactic administration during disease induction. IVIG derived Fc fragments are not required for protection against EAE, since administration of F(ab')2 fragments fully recapitulated the clinical efficacy of IVIG. F(ab')2-treated mice showed a substantial decrease in splenic effector T cell expansion and cytokine production (GM-CSF, IFN-gamma, IL-17A) 9 days after immunization. Inhibition of effector T cell responses was not associated with an increase in total numbers of Tregs but with decreased activation of innate myeloid cells such as neutrophils, monocytes, and dendritic cells. Therapeutically effective IVIG-derived F(ab')2 fragments inhibited adjuvant induced innate immune cell activation as determined by IL-12/23 p40 production and recognized mycobacterial antigens contained in Freund's complete adjuvant which is required for induction of active EAE. CONCLUSIONS: Our data indicate that F(ab')2-mediated neutralization of adjuvant contributes to the therapeutic efficacy of anti-inflammatory IgG. These findings might partly explain the discrepancy of IVIG efficacy in EAE and MS. PMID- 26893158 TI - Vitamin D attenuates inflammation in CFTR knockdown intestinal epithelial cells but has no effect in cells with intact CFTR. AB - The cystic fibrosis (CF) intestine is characterized by chronic inflammation. CF patients are instructed to ingest supplemental vitamin D on a daily basis thereby exposing their intestinal tract to pharmacological amounts of this vitamin. It has been shown that vitamin D exerts intestinal anti-inflammatory properties. We therefore postulate that vitamin D may be beneficial in the management of CF intestinal inflammation by attenuating cellular inflammatory responses. In this study, we investigated the anti-inflammatory effects of the oral form of vitamin D3 (cholecalciferol) and its metabolites, 25-hydroxyvitamin D3 and 1,25 dihydroxyvitamin D3, on cytokine-induced inflammatory responses in intestinal epithelial Caco-2/15 cells with intact expression of CF transmembrane conductance regulator (CFTR) and knockdown for CFTR. We show that 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 inhibited p38MAPK phosphorylation and that these effects were not mediated by changes in the expression of MAPK phosphatase-1 (MKP-1). However, 1,25-dihydroxyvitamin D3 exhibited superior anti-inflammatory effects as it furthermore reduced cytokine-induced NF-kappaB nuclear translocation and interleukin-8 mRNA stability and secretion. Intriguingly, the anti-inflammatory effects of vitamin D metabolites were only observed in CFTR knockdown cells, which may be explained by alterations in its catabolism associated with changes in CYP24A1 expression. These observations were supported in vivo whereby Cftr(-/ ) mice fed large amounts of vitamin D3 for 2 mo led to a reduction in the number of eosinophils and apoptotic cells in the duodenal mucosa of females but not males. Altogether, these findings suggest that vitamin D exerts intestinal anti inflammatory actions under specific circumstances and may thus prove beneficial in CF. PMID- 26893157 TI - Prucalopride exerts neuroprotection in human enteric neurons. AB - Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 +/- 0.1% of neuronal survival vs. 33.3 +/- 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well known enterokinetic effect. PMID- 26893160 TI - Selective portal vein injection for the design of syngeneic models of liver malignancy. AB - Liver metastases are the most frequent cause of death due to colorectal cancer (CRC). Syngeneic orthotopic animal models, based on the grafting of cancer cells or tissue in host liver, are efficient systems for studying liver tumors and their (patho)physiological environment. Here we describe selective portal vein injection as a novel tool to generate syngeneic orthotopic models of liver tumors that avoid most of the weaknesses of existing syngeneic models. By combining portal vein injection of cancer cells with the selective clamping of distal liver lobes, tumor growth is limited to specific lobes. When applied on MC-38 CRC cells and their mouse host C57BL6, selective portal vein injection leads with 100% penetrance to MRI-detectable tumors within 1 wk, followed by a steady growth until the time of death (survival ~7 wk) in the absence of extrahepatic disease. Similar results were obtained using CT-26 cells and their syngeneic Balb/c hosts. As a proof of principle, lobe-restricted liver tumors were also generated using Hepa1-6 (C57BL6-syngeneic) and TIB-75 (Balb/c-syngeneic) hepatocellular cancer cells, demonstrating the general applicability of selective portal vein injection for the induction of malignant liver tumors. Selective portal vein injection is technically straightforward, enables liver invasion via anatomical routes, preserves liver function, and provides unaffected liver tissue. The tumor models are reproducible and highly penetrant, with survival mainly dependent on the growth of lobe-restricted liver malignancy. These models enable biological studies and preclinical testing within short periods of time. PMID- 26893161 TI - Cyclophilin D regulates necrosis, but not apoptosis, of murine eosinophils. AB - Eosinophil degranulation and clusters of free extracellular granules are frequently observed in diverse diseases, including atopic dermatitis, nasal polyposis, and eosinophilic esophagitis. Whether these intact granules are released by necrosis or a biochemically mediated cytolysis remains unknown. Recently, a peptidyl-prolyl isomerase located within the mitochondrial matrix, cyclophilin D (PPIF), was shown to regulate necrotic, but not apoptotic, cell death in vitro in fibroblasts, hepatocytes, and cardiomyocytes. Whether cyclophilin D regulates necrosis in hematopoietic cells such as eosinophils remains unknown. We used PPIF-deficient (Ppif(-/-)) mice to test whether cyclophilin D is required for regulating eosinophil necrosis. PPIF deficiency did not affect eosinophil development or maturation at baseline. After in vitro ionomycin or H2O2 treatment, Ppif(-/-) eosinophils were significantly protected from Ca(2+) overload- or oxidative stress-induced necrosis. Additionally, Ppif(-/ ) eosinophils demonstrated significantly decreased necrosis, but not apoptosis, in response to Siglec-F cross-linking, a stimulus associated with eosinophil mediated processes in vitro and in vivo. When treated with apoptosis inducers, Ppif(+/+) and Ppif(-/-) eosinophils exhibited no significant difference in apoptosis or secondary necrosis. Finally, in a dextran sodium sulfate-induced colitis model, although levels of colitogenic cytokines and eosinophil-selective chemokines were comparable between Ppif(+/+) and Ppif(-/-) mice, the latter exhibited decreased clinical outcomes. This correlated with significantly reduced eosinophil cytolysis in the colon. Collectively, our present studies demonstrate that murine eosinophil necrosis is regulated in vitro and in vivo by cyclophilin D, at least in part, thus providing new insight into the mechanism of eosinophil necrosis and release of free extracellular granules in eosinophil-associated diseases. PMID- 26893162 TI - Age-related changes of vitamin E: alpha-tocopherol levels in plasma and various tissues of mice and hepatic alpha-tocopherol transfer protein. AB - PURPOSE: Despite numerous studies on the RRR- and all-rac-alpha-tocopherol isoform of vitamin E (VE) during aging, this relationship has not been examined in specific tissues. Since alpha-tocopherol is the most abundant of VE's eight isoforms, and VE is an important antioxidant that impacts the aging process, we analyzed alpha-tocopherol levels in plasma and tissues of mice at progressive ages. Moreover, we examined protein and mRNA expression levels of hepatic alpha tocopherol transfer protein (alpha-TTP), which specifically binds alpha tocopherol, during aging. METHODS: The alpha-tocopherol levels in plasma, liver, cerebrum, hippocampus, cerebellum, heart, kidney, epididymal adipose tissue, testis, pancreas, soleus muscle, plantaris muscle, and duodenum from male C57BL/6NCr mice at 3, 6, 12, 18, and 24 months of age were determined by HPLC and fluorescence detection. Also, hepatic alpha-TTP protein and mRNA expression levels were analyzed by Western blot and qPCR, respectively. RESULTS: Tissue specific, age-related changes of alpha-tocopherol levels normalized by tissue weight were observed in the liver, cerebrum, hippocampus, cerebellum, heart, kidney, and epididymal adipose tissue. Specifically, alpha-tocopherol levels in epididymal adipose tissue increased greatly as mice aged from 6 to 24 months. Although hepatic alpha-TTP protein levels also showed age-related changes, alpha TTP mRNA expression levels measured after overnight fasting were not altered. CONCLUSIONS: In this study, we determined that alpha-tocopherol levels and hepatic alpha-TTP protein levels of mice undergo significant tissue-specific, age related changes. This is the first report to investigate VE in terms of the alpha tocopherol levels in plasma and various tissues of mice and hepatic alpha-TTP protein levels during aging. PMID- 26893163 TI - Regulation of cancer-related genes - Cyp1a1, Cyp1b1, Cyp19, Nqo1 and Comt - expression in beta-naphthoflavone-treated mice by miroestrol. AB - OBJECTIVE: The effects of miroestrol (MR), an active phytoestrogen from Pueraria candollei var. mirifica, on expression of cancer-related genes were determined. METHODS: Seven-week-old female ICR mice (n = 5 each) were subcutaneously administered estradiol (E2, 0.5 mg/kg/day) or MR (0.5 or 5 mg/kg/day) daily for 7 days. Some were given ER or MR in combination with beta-naphthoflavone (BNF, 30 mg/kg/day) for the last 3 days. The expression of cancer-related genes including cytochrome P450 1A (Cyp1a), cytochrome P450 1B1 (Cyp1b1), aromatase P450 (Cyp19), NAD(P)H: quinone oxidoreductase 1 (Nqo1) and catechol-O-methyltransferase (Comt) were evaluated. KEY FINDINGS: In the presence of BNF, MR suppressed hepatic CYP1A1 activity and CYP1A2 activity, expression of CYP1B1 mRNA and expression of CYP1A1/2 and CYP1B1 protein. E2, by contrast, did not. MR restored expression levels of hepatic NQO1 and uterine COMT in BNF-treated mice. Furthermore, MR increased expression of uterine CYP19 to the same extent as E2. CONCLUSION: MR may be superior to E2 as it downregulates expression of CYP1. Moreover, MR normalized expression of both NQO1 and COMT, the protective enzymes, in murine liver and uteri. These results support the use of MR as an alternative supplement for menopausal women, MR having the extra benefit of reducing cancer risk. PMID- 26893164 TI - Cyclodextrin-clicked silica/CdTe fluorescent nanoparticles for enantioselective recognition of amino acids. AB - Fluorescent sensors based on semiconductor quantum dots (QDs) have been immensely investigated for achiral molecular recognition. For chiral discrimination of amino acids (AAs), we herein report a versatile fluorescent sensor, i.e., CdTe QDs encapsulated with cyclodextrin (CD) clicked silica via layer-by-layer modification. The as-obtained hybrid molecular recognition platform exhibited excellent chirality sensing of AAs at micromolar concentrations in water. By taking advantage of the inclusion complexation of CD and the optical properties of the QD core, chiral discrimination was realized on the basis of the different binding energies of the CD-AA enantiomer complexes, as revealed using density functional theory calculation. The fluorescent probe exhibited linearly enhanced photoluminescence with increased concentration of d-histidine at 0-60 MUM and L histidine at 0-20 MUM. These water-soluble fluorescent sensors using a chiral host with a covalently linked chromophore may find applications in the robust sensing of a wide range of achiral and chiral molecules in water. PMID- 26893165 TI - Analysis of breed effects on semen traits in light horse, warmblood, and draught horse breeds. AB - In the present study, systematic effects on semen quality traits were investigated in 381 stallions representing 22 breeds. All stallions were used for AI either at the Lower Saxon National Stud Celle or the North Rhine-Westphalian National Stud Warendorf. A total of 71,078 fresh semen reports of the years 2001 to 2014 were edited for analysis of gel-free volume, sperm concentration, total number of sperm, progressive motility, and total number of progressively motile sperm. Breed differences were studied for warmblood and light horse breeds of both national studs (model I) and for warmblood breeds and the draught horse breed Rhenish German Coldblood from the North Rhine-Westphalian National stud (model II) using mixed model procedures. The fixed effects of age class, year, and month of semen collection had significant influences on all semen traits in both analyses. A significant influence of the horse breed was found for all semen traits but gel-free volume in both statistical models. Comparing warmblood and light horse stallions of both national studs, we observed highest sperm concentrations, total numbers of sperm, and total numbers of progressively motile sperm in Anglo-Arabian stallions. The draught horse breed Rhenish German Coldblood had the highest least squares means for gel-free volume, whereas all other investigated semen traits were significantly lower in this breed compared to the warmblood stallions under study. The variance components among stallions within breeds were significant for all semen traits and accounted for 40% to 59% of the total variance. The between-breed-variance among stallions was not significant underlining the similar size of the random stallion effect in each of the horse breeds analyzed here. In conclusion, breed and stallion are accounting for a significant proportion of the variation in semen quality. PMID- 26893159 TI - Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer. AB - The last decade has witnessed remarkable progress in the utilization of natural products for the prevention and treatment of human cancer. Many agents now in the pipeline for clinical trial testing have evolved from our understanding of how human nutritional patterns account for widespread differences in cancer risk. In this review, we have focused on many of these promising agents arguing that they may provide a new strategy for cancer control: natural products once thought to be only preventive in their mode of action now are being explored for efficacy in tandem with cancer therapeutics. Natural products may reduce off-target toxicity of therapeutics while making cancers more amenable to therapy. On the horizon is the use of certain natural products, in their own right, as mitigants of late stage cancer, a new frontier for small-molecule natural product drug discovery. PMID- 26893166 TI - Viability and DNA fragmentation of rainbow trout embryos (Oncorhynchus mykiss) obtained from eggs stored at 4 degrees C. AB - In vitro storage of salmonid eggs leads to aging of the cells causing a decline in quality and reducing their capacity to develop and produce embryos. The quality of salmonid embryos is assessed by morphologic analyses; however, data on the application of biomarkers to determine the cell viability and DNA integrity of embryos in these species are limited. The aim of this study was to evaluate the effect on embryo development, viability and DNA fragmentation in the embryonic cells of in vitro storage time at 4 degrees C of rainbow trout (Oncorhynchus mykiss) eggs. The embryos were obtained by IVF from eggs stored for 0 (control), 48, and 96 hours at 4 degrees C. At 72 hours after fertilization, dechorionated embryos were examined to determine percentages of developed embryos (embryos with normal cell division morphology), viability (LIVE/DEAD sperm viability kit), and DNA integrity (terminal deoxynucleotidyl transferase [TdT] dUTP nick-end labeling assay). The percentage of developing embryos decreased (P < 0.05) with storage time of the eggs (95.10 +/- 2.55; 88.14 +/- 4.50; 79.99 +/- 6.60 for 0, 48, and 96 hours, respectively). Similarly, cell viability decreased (P < 0.05; 96.07 +/- 7.15; 80.42 +/- 8.55; 77.47 +/- 7.88 for 0, 48, and 96 hours, respectively), and an increase (P < 0.05) in DNA fragmentation in the embryos was observed at 96-hour storage. A positive correlation was found between cell DNA fragmentation and storage time (r = 0.8173; P < 0.0001). The results revealed that terminal deoxynucleotidyl transferase [TdT] dUTP nick-end labeling assay technique is reliable mean to assess the state of the DNA in salmonid embryos and that in vitro eggs storage for 96h reduces embryo development and cell DNA integrity. DNA integrity evaluation constitutes a biomarker of the quality of the ova and resulting embryos so as to predict their capacity to produce good-quality embryos in salmonids, particularly under culture conditions. PMID- 26893167 TI - Prostatic abscess in a patient with ST-elevation myocardial infarction: a case report. AB - BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI), urinary tract infection is the most common infection-related complication. Prostatic abscess in a patient with STEMI is very rare. CASE PRESENTATION: We report the case of a 49-year-old Japanese man who developed fever and shaking chills during hospitalization for STEMI. We initially diagnosed catheter-associated urinary tract infection. However, subsequent contrast-enhanced computed tomography revealed multiple large abscesses in his prostate. We decided to treat with antimicrobial agents alone because the patient was receiving dual-antiplatelet therapy and discontinuation is very high risk for in-stent thrombosis. The patient recovered remarkably after treatment without drainage or surgery. CONCLUSIONS: Here, we described the world's first reported case of prostatic abscess in an immunocompetent patient with STEMI. Early removal of indwelling bladder catheters in patients with STEMI receiving dual-antiplatelet therapy is important to avoid development of prostatic abscess. Furthermore, unnecessary invasive instrumentation should be avoided or limited to diminish the risk of infections. PMID- 26893169 TI - Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses. AB - Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserved hemagglutinin fusion peptide (FP). Interestingly, FP antagonizes interferon production induced by membrane fusion or IAV but not by cGAMP or DNA. Similar to the enveloped RNA viruses, membrane fusion stimulates interferon production in a STING-dependent but cGAS-independent manner. Abolishment of this pathway led to reduced interferon production and impaired control of enveloped RNA viruses. Thus, enveloped RNA viruses stimulate a cGAS independent STING pathway, which is targeted by IAV. PMID- 26893170 TI - Pharmacokinetics of oral and intravenous melatonin in healthy volunteers. AB - BACKGROUND: The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers. METHODS: The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1/2 absorption, t max, C max, t 1/2 elimination, AUC 0-infinity, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0 infinity were determined for intravenous melatonin. RESULTS: Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ significantly between the study days (P = 0.067). Mean (SD) t 1/2 absorption of oral melatonin was 6.0 (3.1) min. Mean t max was 40.8 (17.8) min with a median (IQR) C max of 3550.5 (2500.5-8057.5) pg ml(-1). Mean t 1/2 elimination was 53.7 (7.0) min. Median absolute bioavailability was 2.5 (1.7-4.7) %. Median C max after short iv infusion of melatonin was 389,875.0 (174,775.0-440,362.5) pg ml( 1). Mean t 1/2 elimination was 39.4 (3.6) min, mean V d 1.2 (0.6) l kg(-1) and mean CL 0.0218 (0.0102) l min(-1) kg(-1). CONCLUSIONS: This cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %. TRIAL REGISTRATION: Eudra-CT number: 2013-000205-23 (initial registration 27.03.2013). Clinicaltrials.gov Identifier: NCT01923974 (initial registration 08.08.2013). PMID- 26893172 TI - Carbon fiducials for large choroidal melanoma treated with gamma knife radiosurgery. PMID- 26893168 TI - A Potential Contribution of Chemokine Network Dysfunction to the Depressive Disorders. AB - In spite of many years of research, the pathomechanism of depression has not yet been elucidated. Among many hypotheses, the immune theory has generated a substantial interest. Up till now, it has been thought that depression is accompanied by the activation of inflammatory response and increase in pro inflammatory cytokine levels. However, recently this view has become controversial, mainly due to the family of small proteins called chemokines. They play a key role in the modulation of peripheral function of the immune system by controlling immune reactions, mediating immune cell communication, and regulating chemotaxis and cell adhesion. Last studies underline significance of chemokines in the central nervous system, not only in the neuromodulation but also in the regulation of neurodevelopmental processes, neuroendocrine functions and in mediating the action of classical neurotransmitters. Moreover, it was demonstrated that these proteins are responsible for maintaining interactions between neuronal and glial cells both in the developing and adult brain also in the course of diseases. This review outlines the role of chemokine in the central nervous system under physiological and pathological conditions and their involvement in processes underlying depressive disorder. It summarizes the most important data from experimental and clinical studies. PMID- 26893171 TI - The risk of new-onset cancer associated with HFE C282Y and H63D mutations: evidence from 87,028 participants. AB - To investigate the association between mutation of HFE (the principal pathogenic gene in hereditary haemochromatosis) and risk of cancer, we conducted a meta analysis of all available case-control or cohort studies relating to two missense mutations, C282Y and H63D mutations. Eligible studies were identified by searching databases including PubMed, Embase and the ISI Web of Knowledge. Overall and subgroup analyses were performed and odds ratios (ORs) combined with 95% confidence intervals (CIs) were applied to evaluate the association between C282Y mutation, H63D mutation and cancer risk. Sensitivity and cumulative analyses were used to evaluate the stability of the results. A total of 36 eligible studies were included, comprising 13,680 cases and 73,348 controls. C282Y was significantly associated with elevated cancer risk in a recessive genetic model (OR: 1.991, 95% CI: 1.448-2.737). On subgroup analysis stratified by cancer type, statistically significantly increased cancer risks were found for breast cancer, colorectal cancer and hepatocellular carcinoma in a recessive model. When stratified by territory, a significantly increased risk of cancer was found in Oceanic populations in a recessive model and in Asian populations in an allele model and dominant model. H63D mutation did not significantly increase overall cancer risk in any genetic model. However, when, stratified by territory, an increased cancer risk was found in the Asian population in an allele and dominant. C282Y but not H63D mutation was related to elevated cancer risk. Further large-scale studies considering gene-environment interactions and functional research should be conducted to further investigate this association. PMID- 26893173 TI - Implications of Misclassification Errors in Empirical Studies of Adolescent Smoking Behaviours. AB - Misclassification errors in a dependent variable can introduce attenuation bias to covariate effects in a binary choice model. Misreporting of smoking behaviours by adolescents has been widely documented. However, the consequence in empirical studies of adolescent smoking participation has received little attention. This study uses the Health Survey for England (HSE) to investigate the extent and implication of misclassification errors in self-reported smoking among adolescents aged 11-15 years. The HSE contains both a self-reported smoking component and an objective measure of smoking obtained from saliva cotinine assays. Saliva cotinine concentration >=12 ng/ml is considered the 'true' indicator of adolescent smoking participation against which self-reported smoking is compared. The findings show that smoking is misreported in this age group, resulting in a downwards bias of marginal effect estimates. Given the widespread use of self-reported smoking data, this study explores the performance of the Hausman, Abrevaya and Scott-Morton-modified maximum likelihood estimation (HAS approach) in recovering true estimates of covariate effects. In this context, the HAS approach performs better when the misclassification probabilities are treated as constants compared with when they are treated as conditionally dependent parameters. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26893175 TI - Self-Adaptive Spike-Time-Dependent Plasticity of Metal-Oxide Memristors. AB - Metal-oxide memristors have emerged as promising candidates for hardware implementation of artificial synapses - the key components of high-performance, analog neuromorphic networks - due to their excellent scaling prospects. Since some advanced cognitive tasks require spiking neuromorphic networks, which explicitly model individual neural pulses ("spikes") in biological neural systems, it is crucial for memristive synapses to support the spike-time dependent plasticity (STDP). A major challenge for the STDP implementation is that, in contrast to some simplistic models of the plasticity, the elementary change of a synaptic weight in an artificial hardware synapse depends not only on the pre-synaptic and post-synaptic signals, but also on the initial weight (memristor's conductance) value. Here we experimentally demonstrate, for the first time, an STDP behavior that ensures self-adaptation of the average memristor conductance, making the plasticity stable, i.e. insensitive to the initial state of the devices. The experiments have been carried out with 200-nm Al2O3/TiO2-x memristors integrated into 12 * 12 crossbars. The experimentally observed self-adaptive STDP behavior has been complemented with numerical modeling of weight dynamics in a simple system with a leaky-integrate-and-fire neuron with a random spike-train input, using a compact model of memristor plasticity, fitted for quantitatively correct description of our memristors. PMID- 26893176 TI - Erratum to: An ecological risk assessment of heavy metal contamination in the surface sediments of Bosten Lake, northwest China. PMID- 26893174 TI - Heme oxygenase-1 induction attenuates imiquimod-induced psoriasiform inflammation by negative regulation of Stat3 signaling. AB - Heme oxygenase-1 (HO-1), a stress-inducible protein with a potential anti inflammatory effect, plays an important role in skin injury and wound healing. However, the function of HO-1 in cutaneous inflammatory diseases, such as psoriasis, remains unknown. The abnormal activation of Stat3, a known transcription factor that induces inflammation and regulates cell differentiation, is directly involved in the pathogenesis and development of psoriasis. Hence, targeting Stat3 is potentially beneficial in the treatment of psoriasis. In this study, HO-1 activation significantly alleviated the disease related pathogenesis abnormality. To determine the mechanism by which HO-1 exerts immune protection on Th17-related cytokines, IL6/IL22-induced Stat3 activation was significantly suppressed, accompanied by decreased cell proliferation and reversed abnormal cell proliferation. Importantly, HO-1-induced Stat3 suppression was mediated through the activation of protein tyrosine phosphatase SHP-1. Overall, our study provides direct evidence indicating that HO-1 might be a useful therapeutic target for psoriasis. SHP-1-mediated suppression of Stat3 activation after HO-1 activation is a unique molecular mechanism for the regulation of Stat3 activation. PMID- 26893177 TI - Biotransformation of petroleum asphaltenes and high molecular weight polycyclic aromatic hydrocarbons by Neosartorya fischeri. AB - Neosartorya fischeri, an Aspergillaceae fungus, was evaluated in its capacity to transform high molecular weight polycyclic aromatics hydrocarbons (HMW-PAHs) and the recalcitrant fraction of petroleum, the asphaltenes. N. fischeri was able to grow in these compounds as sole carbon source. Coronene, benzo(g,h,i)perylene, and indeno(1,2,3-c,d)pyrene, together with the asphaltenes, were assayed for fungal biotransformation. The transformation of the asphaltenes and HMW-PAHs was confirmed by reverse-phase high-performance liquid chromatography (HPLC), nano-LC mass spectrometry, and IR spectrometry. The formation of hydroxy and ketones groups on the PAH molecules suggest a biotransformation mediated by monooxygenases such as cytochrome P450 system (CYP). A comparative microarray with the complete genome from N. fischeri showed three CYP monooxygenases and one flavin monooxygenase genes upregulated. These findings, together with the internalization of aromatic substrates into fungal cells and the microsomal transformation of HMW-PAHs, strongly support the role of CYPs in the oxidation of these recalcitrant compounds. PMID- 26893178 TI - Operator decision support system for integrated wastewater management including wastewater treatment plants and receiving water bodies. AB - An operator decision support system (ODSS) is proposed to support operators of wastewater treatment plants (WWTPs) in making appropriate decisions. This system accounts for water quality (WQ) variations in WWTP influent and effluent and in the receiving water body (RWB). The proposed system is comprised of two diagnosis modules, three prediction modules, and a scenario-based supporting module (SSM). In the diagnosis modules, the WQs of the influent and effluent WWTP and of the RWB are assessed via multivariate analysis. Three prediction modules based on the k-nearest neighbors (k-NN) method, activated sludge model no. 2d (ASM2d) model, and QUAL2E model are used to forecast WQs for 3 days in advance. To compare various operating alternatives, SSM is applied to test various predetermined operating conditions in terms of overall oxygen transfer coefficient (Kla), waste sludge flow rate (Qw), return sludge flow rate (Qr), and internal recycle flow rate (Qir). In the case of unacceptable total phosphorus (TP), SSM provides appropriate information for the chemical treatment. The constructed ODSS was tested using data collected from Geumho River, which was the RWB, and S WWTP in Daegu City, South Korea. The results demonstrate the capability of the proposed ODSS to provide WWTP operators with more objective qualitative and quantitative assessments of WWTP and RWB WQs. Moreover, the current study shows that ODSS, using data collected from the study area, can be used to identify operational alternatives through SSM at an integrated urban wastewater management level. PMID- 26893179 TI - Mutagenicity assessment of aerosols in emissions from domestic combustion processes. AB - Domestic biofuel combustion is one of the major sources of regional and local air pollution, mainly regarding particulate matter and organic compounds, during winter periods. Mutagenic and carcinogenic activity potentials of the ambient particulate matter have been associated with the fraction of polycyclic aromatic hydrocarbons (PAH) and their oxygenated (OPAH) and nitrogenated (NPAH) derivatives. This study aimed at assessing the mutagenicity potential of the fraction of this polycyclic aromatic compound in particles (PM10) from domestic combustion by using the Ames assays with Salmonella typhimurium TA98 and TA100. Seven biofuels, including four types of pellets and three agro-fuels (olive pit, almond shell and shell of pine nuts), were tested in an automatic pellet stove, and two types of wood (Pinus pinaster, maritime pine, and Eucalyptus globulus, eucalypt) were burned in a traditional wood stove. For this latter appliance, two combustion phases-devolatilisation and flaming/smouldering-were characterised separately. A direct-acting mutagenic effect for the devolatilisation phase of pine combustion and for both phases of eucalypt combustion was found. Almond shell revealed a weak direct-acting mutagenic effect, while one type of pellets, made of recycled wastes, and pine (devolatilisation) presented a cytotoxic effect towards strain TA100. Compared to the manually fired appliance, the automatic pellet stove promoted lower polyaromatic mutagenic emissions. For this device, only two of the studied biofuels presented a weak mutagenic or cytotoxic potential. PMID- 26893180 TI - Stability and heavy metal distribution of soil aggregates affected by application of apatite, lime, and charcoal. AB - Only a few studies have been reported on the stability and heavy metal distribution of soil aggregates after soil treatments to reduce the availability of heavy metals. In this study, apatite (22.3 t ha(-1)), lime (4.45 t ha(-1)), and charcoal (66.8 t ha(-1)) were applied to a heavy metal-contaminated soil for 4 years. The stability and heavy metal distribution of soil aggregates were investigated by dry and wet sieving. No significant change in the dry mean weight diameter was observed in any treatments. Compared with the control, three amendment treatments significantly increased the wet mean weight diameter, but only charcoal treatment significantly increased the wet aggregate stability. The soil treatments increased the content of soil organic carbon, and the fraction 0.25-2 mm contained the highest content of soil organic carbon. Amendments' application slightly increased soil total Cu and Cd, but decreased the concentrations of CaCl2 -extractable Cu and Cd except for the fraction <0.053 mm. The fractions >2 and 0.25-2 mm contained the highest concentrations of CaCl2 extractable Cu and Cd, accounted for about 74.5-86.8 % of CaCl2-extractable Cu and Cd in soil. The results indicated that amendments' application increased the wet soil aggregate stability and decreased the available Cu and Cd. The distribution of available heavy metals in wet soil aggregates was not controlled by soil aggregate stability, but possibly by soil organic carbon. PMID- 26893183 TI - Ian Tomlinson. PMID- 26893182 TI - Speciation of dissolved copper in human impacted freshwater and saltwater lakes. AB - China's natural waters are experiencing an increasingly anthropogenic perturbation widely including acidification and hypoxia, and toxic metals including copper (Cu) are subject to a series of reactions including chemical speciation and transformation. However, there is still little information available regarding such alterations of metal behaviors in China's natural waters. By using solid phase extraction technique, this study for the first time measured total dissolved Cu, and different Cu species: toxic labile Cu (referred to those free cupric ions and some weakly organic compounds adsorbed onto Chelex 100 resins), the organic refractory Cu (referred to those adsorbed onto C18 resins after passing through Chelex-100 resins), and residual Cu (obtained by subtracting labile and organic refractory fractions from the total) in a freshwater lake (the Lover) and a saltwater lagoon (the Yundang) in Xiamen, China. Our results demonstrated that both waters were characterized with relatively low levels of total dissolved Cu (5-10 nM), as a result of a net removal process dominated by particle adsorption and precipitation. Relatively high proportion of organic refractory Cu (as high as 50 %) was observed in the saltwater Yundang lagoon as a result of organic matter production and/or discharges followed by complexation nearby. On the other hand, the toxic labile Cu accounted for >40 % of the total dissolved Cu pool in these waters, and particularly the increased proportion of toxic labile Cu (as high as 70 %) occurred in the bottom sulfidic Lover Lake. Our study provides clear evidence that toxic labile Cu could be transformed under reducing environments such as deep sulfidic waters of the Lover Lake (Xiamen, China), and the releases of toxic labile metals are increasingly threatening nearby aquatic ecosystems. PMID- 26893181 TI - Prevalence of plasmid-mediated multidrug resistance determinants in fluoroquinolone-resistant bacteria isolated from sewage and surface water. AB - Fluoroquinolones (FQs) are fully synthetic broad-spectrum antibacterial agents that are becoming increasingly popular in the treatment of clinical and veterinary infections. Being excreted during treatment, mostly as active compounds, their biological action is not limited to the therapeutic site, but it is moved further as resistance selection pressure into the environment. Water environment is an ideal medium for the aggregation and dissemination of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs), which can pose a serious threat to human health. Because of this, the aim of this study was to determine the number of fluoroquinolone-resistant bacteria (FQRB) and their share in total heterotrophic plate counts (HPC) in treated wastewater (TWW), and upstream and downstream river water (URW, DRW) samples where TWW is discharged. The spread of plasmid-mediated quinolone resistance (PMQR) determinants and the presence/absence of resistance genes to other most popular antibiotic groups (against tetracyclines and beta-lactams) in selected 116 multiresistant isolates were investigated. The share of FQRB in total HPC in all samples was rather small and ranged from 0.7 % in URW samples to 7.5 % in TWW. Bacteria from Escherichia (25.0 %), Acinetobacter (25.0 %), and Aeromonas (6.9 %) genera were predominant in the FQRB group. Fluoroquinolone resistance was mostly caused by the presence of the gene aac(6')-1b-cr (91.4 %). More rarely reported was the occurrence of qnrS, qnrD, as well as oqxA, but qnrA, qnrB, qepA, and oqxB were extremely rarely or never noted in FQRB. The most prevalent bacterial genes connected with beta-lactams' resistance in FQRB were bla TEM, bla OXA, and bla CTX-M. The bla SHV was less common in the community of FQRB. The occurrence of bla genes was reported in almost 29.3 % of FQRB. The most abundant tet genes in FQRB were tet(A), tet(L), tet(K), and tet(S). The prevalence of tet genes was observed in 41.4 % of FQRB. The highest prevalence of multidrug resistant (MDR) microorganisms was detected in TWW and DRW samples. It indicates that discharged TWW harbors multiresistant bacterial strains and that mobile PMQR and ARGs elements may have a selective pressure for species affiliated to bacteria in the river water. PMID- 26893186 TI - Ultrasensitive sub-pg/ml determination of tiotropium bromide in human plasma by 2D-UHPLC-MS/MS: challenges and solutions. AB - BACKGROUND: To adequately support pharmacokinetic evaluations of tiotropium bromide in planned clinical studies. It was desirable to measure it with a LLOQ of sub pg/ml. RESULTS: A sensitive bioanalytical method for the determination of tiotropium in human plasma sample was successfully developed and validated in the range of 0.2-100 pg/ml. The method was successfully applied to support two clinical studies of over 3000 samples. The overall incurred sample reanalysis passing rate was 93.7%. CONCLUSION: The combination of a dual stage liquid-liquid extraction and a 2D ultra-HPLC greatly reduced matrix effects and increased assay sensitivity. When developing effective ultrasensitive assays, it is imperative to balance the aspects related to sensitivity with those that will ensure assay ruggedness. PMID- 26893185 TI - Hypertension unawareness among Chinese patients with first-ever stroke. AB - BACKGROUND: The low rates of hypertension treatment and control, partly due to its unawareness, are the main causes of the high stroke incidence in China. The purpose of this study was to evaluate hypertension unawareness amongst patients with first-ever stroke and to detect factors associated with its unawareness. METHODS: We selected those diagnosed with hypertension from patients with first ever stroke registered in the Nanjing Stroke Registry Program between 2004 and 2014. These hypertensives were divided as being aware or unaware of their hypertension by using a brief questionnaire conducted shortly after the stroke. Multivariate logistic regression analysis was performed to identify potential factors associated with hypertension unawareness. RESULTS: Of the 5309 patients with first-ever stroke, 3732 (70.3%) were diagnosed with hypertension. Among which, 593 (15.9%) were unaware of their hypertension at the time of stroke onset. Lower-level of education (primary school or illiteracy) and smoking were associated positively with hypertension unawareness; while advanced age, overweight, diabetes mellitus, heart diseases and family history of stroke were associated negatively with hypertension unawareness. Annual data analyzed indicated that the rate of hypertension awareness increased during the past 11 years (r = 0.613, P = 0.045 for trends). CONCLUSIONS: A substantial proportion (15.9%) of Chinese patients with hypertension had not been aware of this covert risk until an overt stroke occurred. Hypertension unawareness was associated with lower educational levels and smoking, which address the importance of health education especially in these individuals. PMID- 26893187 TI - Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. AB - Androgenetic alopecia is an androgen-induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long-term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5-alpha-reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open-label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end-points included adverse event assessment, incidence of drug-related adverse event and premature discontinuations. Secondary end-points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug-related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long-term safety, tolerability and efficacy within this study population. PMID- 26893188 TI - Synthesis and transistor application of the extremely extended phenacene molecule, [9]phenacene. AB - Many chemists have attempted syntheses of extended pi-electron network molecules because of the widespread interest in the chemistry, physics and materials science of such molecules and their potential applications. In particular, extended phenacene molecules, consisting of coplanar fused benzene rings in a repeating W-shaped pattern have attracted much attention because field-effect transistors (FETs) using phenacene molecules show promisingly high performance. Until now, the most extended phenacene molecule available for transistors was [8]phenacene, with eight benzene rings, which showed very high FET performance. Here, we report the synthesis of a more extended phenacene molecule, [9]phenacene, with nine benzene rings. Our synthesis produced enough [9]phenacene to allow the characterization of its crystal and electronic structures, as well as the fabrication of FETs using thin-film and single-crystal [9]phenacene. The latter showed a field-effect mobility as high as 18 cm(2) V(-1) s(-1), which is the highest mobility realized so far in organic single-crystal FETs. PMID- 26893184 TI - Evolution of strategies to improve preclinical cardiac safety testing. AB - The early and efficient assessment of cardiac safety liabilities is essential to confidently advance novel drug candidates. This article discusses evolving mechanistically based preclinical strategies for detecting drug-induced electrophysiological and structural cardiotoxicity using in vitro human ion channel assays, human-based in silico reconstructions and human stem cell-derived cardiomyocytes. These strategies represent a paradigm shift from current approaches, which rely on simplistic in vitro assays that measure blockade of the Kv11.1 current (also known as the hERG current or IKr) and on the use of non human cells or tissues. These new strategies have the potential to improve sensitivity and specificity in the early detection of genuine cardiotoxicity risks, thereby reducing the likelihood of mistakenly discarding viable drug candidates and speeding the progression of worthy drugs into clinical trials. PMID- 26893189 TI - Lithium ions in nanomolar concentration modulate glycine-activated chloride current in rat hippocampal neurons. AB - Lithium salts are successfully used to treat bipolar disorder. At the same time, according to recent data lithium may be considered as a candidate medication for the treatment of neurodegenerative disorders. The mechanisms of therapeutic action of lithium have not been fully elucidated. In particular, in the literature there are no data on the effect of lithium on the glycine receptors. In the present study we investigated the effect of Li(+) on glycine-activated chloride current (IGly) in rat isolated pyramidal hippocampal neurons using patch clamp technique. The effects of Li(+) were studied with two glycine concentrations: 100 MUM (EC50) and 500 MUM (nearly saturating). Li(+) was applied to the cell in two ways: first, by 600 ms co-application with glycine through micropipette (short application), and, second, by addition to an extracellular perfusate for 10 min (longer application). Li(+) was used in the range of concentrations of 1 nM-1 mM. Short application of Li(+) caused two effects: (1) an acceleration of desensitization (a decrease in the time of half-decay, or "tau") of IGly induced by both 100 MUM and 500 MUM glycine, and (2) a reduction of the peak amplitude of the IGly, induced by 100 MUM, but not by 500 MUM glycine. Both effects were not voltage-dependent. Dose-response curves for both effects were N-shaped with two maximums at 100 nM and 1 mM of Li(+) and a minimum at 1 MUM of Li(+). This complex form of dose-response may indicate that the process activated by high concentrations of lithium inhibits the process that is sensitive to low concentrations of lithium. Longer application of Li(+)caused similar effects, but in this case 1 MUM lithium was effective and the dose-effect curves were not N-shaped. The inhibitory effect of lithium ions on glycine activated current suggests that lithium in low concentrations is able to modulate tonic inhibition in the hippocampus. This important property of lithium should be considered when using this drug as a therapeutic agent. PMID- 26893191 TI - Moving Toward Understanding the Proteome Involved in Substance Abuse. PMID- 26893192 TI - Binge Drinking With Protein Kinase C Epsilon: A Role for Mammalian Target of Rapamycin Complex 2? PMID- 26893193 TI - A Critical Role of Brain-Derived Neurotrophic Factor in Alcohol Consumption. PMID- 26893190 TI - Association between cytoplasmic CRABP2, altered retinoic acid signaling, and poor prognosis in glioblastoma. AB - Retinoic acid (RA), a metabolite of vitamin A, is required for the regulation of growth and development. Aberrant expression of molecules involved in RA signaling has been reported in various cancer types including glioblastoma multiforme (GBM). Cellular retinoic acid-binding protein 2 (CRABP2) has previously been shown to play a key role in the transport of RA to retinoic acid receptors (RARs) to activate their transcription regulatory activity. Here, we demonstrate that CRABP2 is predominantly located in the cytoplasm of GBM tumors. Cytoplasmic, but not nuclear, CRABP2 levels in GBM tumors are associated with poor patient survival. Treatment of malignant glioma cell lines with RA results in a dose dependent increase in accumulation of CRABP2 in the cytoplasm. CRABP2 knockdown reduces proliferation rates of malignant glioma cells, and enhances RA-induced RAR activation. Levels of CRYAB, a small heat shock protein with anti-apoptotic activity, and GFAP, an astrocyte-specific intermediate filament protein, are greatly reduced in CRABP2-depleted cells. Restoration of CRYAB expression partially but significantly reversed the effect of CRABP2 depletion on RAR activation. Our combined in vivo and in vitro data indicate that: (i) CRABP2 is an important determinant of clinical outcome in GBM patients, and (ii) the mechanism of action of CRABP2 in GBM involves sequestration of RA in the cytoplasm and activation of an anti-apoptotic pathway, thereby enhancing proliferation and preventing RA-mediated cell death and differentiation. We propose that reducing CRABP2 levels may enhance the therapeutic index of RA in GBM patients. PMID- 26893194 TI - Persisting Differences in the Sensitivity to the Effects of Alcohol: What We Know and Where to Go From Here. PMID- 26893195 TI - Routines for change: how managers can use absorptive capacity to adopt and implement evidence-based practice. AB - AIMS: This paper uses the construct of absorptive capacity to understand how nurse managers can facilitate the adoption and use of evidence-based practice within health-care organisations. BACKGROUND: How health-care organisations adopt and implement innovations such as new evidence-based practices will depend on their absorptive, or learning, capacity. Absorptive capacity manifests as routines, which are the practices, procedures and customs that organisational members use to carry out work and to make work-related decisions. METHODS: Using the construct of absorptive capacity as well as a recent literature review of how health-care organisations take on best practices, we illustrate how the uptake and use of new knowledge, such as evidence-based practices, can be facilitated through the use of routines. IMPLICATIONS FOR NURSING MANAGEMENT: This paper highlights routines that nurse managers can use to foster environments where evidence-based practices can be readily identified, and strategies for facilitating their adoption and implementation. CONCLUSIONS: The construct of absorptive capacity and the use of routines can be used to examine the ways in which nurse managers can adopt, implement and evaluate the use of evidence-based practices. PMID- 26893196 TI - The Critical Criterion on Runaway Shear Banding in Metallic Glasses. AB - The plastic flow of metallic glasses (MGs) in bulk is mediated by nanoscale shear bands, which is known to proceed in a stick-slip manner until reaching a transition state causing catastrophic failures. Such a slip-to-failure transition controls the plasticity of MGs and resembles many important phenomena in natural science and engineering, such as friction, lubrication and earthquake, therefore has attracted tremendous research interest over past decades. However, despite the fundamental and practical importance, the physical origin of this slip-to failure transition is still poorly understood. By tracking the behavior of a single shear band, here we discover that the final fracture of various MGs during compression is triggered as the velocity of the dominant shear band rises to a critical value, the magnitude of which is independent of alloy composition, sample size, strain rate and testing frame stiffness. The critical shear band velocity is rationalized with the continuum theory of liquid instability, physically originating from a shear-induced cavitation process inside the shear band. Our current finding sheds a quantitative insight into deformation and fracture in disordered solids and, more importantly, is useful to the design of plastic/tough MG-based materials and structures. PMID- 26893197 TI - Plant essential oils and potassium metabisulfite as repellents for Drosophila suzukii (Diptera: Drosophilidae). AB - Spotted wing drosophila, Drosophila suzukii, is a globally invasive pest of soft skinned fruit. Females oviposit into ripening fruit and larvae cause direct destruction of tissues. As many plant essential oils are permitted food additives, they may provide a safe means of protecting fruit from D. suzukii infestation in both conventional and organic production systems. Twelve oils and potassium metabisulfite (KMS) were screened in the laboratory as repellents for D. suzukii flies. Most essential oils deterred D. suzukii flies from cotton wicks containing attractive raspberry juice. Peppermint oil was particularly effective, preventing almost all flies from contacting treated wicks and remaining 100% repellent for 6 d post-application. Thyme oil was unique because it caused high male mortality and reduced the number of responding flies compared to other oils. KMS was not found to be repellent to D. suzukii, but may have fumigant properties, particularly at high concentrations. Peppermint oil appears to be the best candidate for field testing to determine the effectiveness and feasibility of using essential oils as part of a push-pull management strategy against D. suzukii. This is the first time that essential oils have been evaluated and proven effective in preventing fruit-infesting flies from contacting attractive stimuli. PMID- 26893199 TI - Dynamic encapsulation and activation of carbonic anhydrase in multivalent dynameric host matrices. AB - A straight-forward carbonic anhydrase activation strategy via dynamic encapsulation has been achieved by direct addition of multivalent amide dynamers into enzyme reaction solutions. PMID- 26893198 TI - Dynamic prediction of risk of liver-related outcomes in chronic hepatitis C using routinely collected data. AB - Accuracy of risk assessments for clinical outcomes in patients with chronic liver disease has been limited given the nonlinear nature of disease progression. Longitudinal prediction models may more accurately capture this dynamic risk. The aim of this study was to construct accurate models of short- and long-term risk of disease progression in patients with chronic hepatitis C by incorporating longitudinal clinical data. Data from the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial were analysed (n = 533 training cohort; n = 517 validation cohort). Outcomes included a composite liver outcome (liver-related death, decompensation, hepatocellular carcinoma (HCC) or liver transplant), decompensation, HCC and overall mortality. Longitudinal models were constructed for risk of outcomes at 1, 3 and 5 years and compared with models using data at baseline only or baseline and a single follow-up time point. A total of 25.1% of patients in the training and 20.8% in the validation cohort had an outcome during a median follow-up of 6.5 years (range 0.5-9.2). The most important predictors were as follows: albumin, aspartate aminotransferase/alanine aminotransferase ratio, bilirubin, alpha-fetoprotein and platelets. Longitudinal models outperformed baseline models with higher true-positive rates and negative predictive values. The areas under the receiver-operating characteristic curve for the composite longitudinal model were 0.89 (0.80-0.96), 0.83 (0.76-0.88) and 0.81 (0.75-0.87) for 1-, 3-, and 5-year risk prediction, respectively. Model performance was retained for decompensation and overall mortality but not HCC. Longitudinal prediction models provide accurate risk assessments and identify patients in need of intensive monitoring and care. PMID- 26893200 TI - Mitochondrial ascorbic acid prevents mitochondrial O2.- formation, an event critical for U937 cell apoptosis induced by arsenite through both autophagic dependent and independent mechanisms. AB - A 16 h exposure of U937 cells to 2.5 uM arsenite promotes superoxide (O2(.-)) formation and inhibition of the activity of aconitase, a O2(.-) sensitive enzyme. Both responses were abolished by the complex I inhibitor rotenone, or by the respiration-deficient phenotype. Interestingly, a similar suppressive effect was mediated by a short term pre-exposure to a low concentration of L-ascorbic acid (AA), previously shown to be actively taken up by the cells and by their mitochondria. The mitochondrial origin of O2(.-) was confirmed by fluorescence microscopy studies, whereas different approaches failed to detect a contribution of NADPH oxidase. Under similar conditions, arsenite induced autophagy as well as a decline in mitochondrial membrane potential resulting in delayed (48 h) apoptosis. Importantly, all these events turned out to be sensitive to treatments associated with prevention of O2(.-) formation, including AA, and were only partially blunted by inhibitors of autophagy. As a final note, the toxic effects mediated by O2(.-)were entirely dependent on its conversion to H2O2. AA-sensitive mitochondrial O2(.-) formation is therefore involved in autophagy and apoptosis induced by arsenite in U937 cells, although part of the lethal response appears mediated by an autophagy-independent mechanism. PMID- 26893201 TI - Family practice in Turkey: Observations from a pilot implementation. AB - OBJECTIVE: Turkey has implemented family practice on a pilot basis as part of the reform in health care, since 2005. This paper aims to understand and describe the prevalent practice patterns and clinic characteristics during the transition period. DESIGN: A cross-sectional descriptive study design was used. SUBJECTS: An online survey was conducted among Turkish GPs working as primary care doctors (without vocational training) during the reform period. Clinic and GP characteristics are analysed with descriptive statistics. RESULTS: List size is an important factor; larger lists lead to shorter consultation time and a longer wait for patients. GPs are generally satisfied with the reform. CONCLUSION: During the transition to family practice access of patients to health care has improved and GPs are satisfied with their job. KEY POINTS: Patients in Turkey have adequate access to primary health care services. The waiting time for consultation is relatively short. Basic prevention activities occupy the majority of the GPs' time. Reducing the panel size and introducing appointment systems may be useful. PMID- 26893202 TI - Imagining future events in patients with unilateral temporal lobe epilepsy. AB - OBJECTIVES: Imagining future events, which contain episodic and non-episodic details, has been found to (1) engage the temporal lobes bilaterally and (2) be impaired in patients with bilateral temporal lobe pathology. Here, we examined whether unilateral temporal lobe dysfunction also impairs the ability to generate future events. DESIGN: Prospective cross-sectional. METHODS: Twenty patients with a history of unilateral temporal lobe epilepsy [TLE; 10 left (LTLE) and 10 right (RTLE)] and 20 normal control (NC) subjects comparable on age, sex and education completed the Adapted Autobiographical Interview, which required recall of past and generation of future events and distinguished episodic (internal) from non episodic (external) details. Participants also completed a battery of neuropsychological tests. RESULTS: Patients with unilateral TLE were significantly impaired in provision of internal details for past and future events, but not in the generation of external details. Examination of detail subcategories revealed that patients with LTLE did exhibit a significant deficit relative to patients with RTLE (and NC) with respect to the generation of perceptual details for both past and future events. Moreover, patients with LTLE generated significantly fewer place details for future events (relative to NC only). The overall number of internal details recalled by patients with LTLE was related to semantic fluency. CONCLUSIONS: Our study provides the first evidence that unilateral temporal lobe dysfunction is associated with not only impaired recall of past, but also the generation of future episodic details. Clinically, deficits in future thinking may reduce motivation and decision-making, and as such adversely impact behavioural regulation and socialization. PRACTITIONER POINTS: Patients with temporal lobe epilepsy generate less details when asked to describe past and potential future events, particularly with regard to details involving specific events, places and perceptions. These same patients are aware of their difficulties in this realm, but judge their past memories as similar in vividness and even more personally significant than the memories generated by control participants. The deficits in generation of future episodic details were particularly pronounced in patients with left temporal lobe epilepsy. Verbal semantic fluency was correlated with the ability to generate future scenarios. PMID- 26893203 TI - Device-in-device: A transcatheter alternative to surgical explantation of a failing atrial septal defect intracardiac prosthesis. AB - A failing intracardiac device is traditionally addressed by open-heart surgery. Surgical explantation of the device, although a simple procedure, carries risks that some patients are not able or willing to cope with. Thus, a nonsurgical option seems desirable in selected cases. We report on four cases of early malfunction of the Polyvinyl Alcohol membrane of Ultrasept IITM CARDIA ASD devices. In all cases, transthoracic echo (TTE) surveillance 4-6 months after the index procedure, depicted significant left-to-right atrial shunts through the center portion of the devices. A second nitinol double disk device with a connecting pin (Lifetech CERATM Multifenestrated ASD device) was implanted over the CARDIA devices, with excellent results. All procedures were uneventful and all patients are asymptomatic with no residual shunts, in short-term follow-up. This device-in-device technique prevents surgical explantation of failing ASD devices, and may become a less invasive option in selected patients. (c) 2016 Wiley Periodicals, Inc. PMID- 26893205 TI - Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography: Outcomes Analysis From 3 Years of Breast Cancer Screening. AB - IMPORTANCE: Breast cancer screening with digital breast tomosynthesis (DBT) combined with digital mammography (DM) decreases false-positive examinations and increases cancer detection compared with screening with DM alone. However, the longitudinal performance of DBT screening is unknown. OBJECTIVES: To determine whether the improved outcomes observed after initial implementation of DBT screening are sustainable over time at a population level and to evaluate the effect of more than 1 DBT screening at the individual level. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of screening mammography metrics was performed for all patients presenting for screening mammography in an urban, academic breast center during 4 consecutive years (DM, year 0; DBT, years, 1-3). The study was conducted from September 1, 2010, to September 30, 2014 (excluding September 2011, which was the transition period from DM to DBT), for a total of 44 468 screening events attributable to a total of 23 958 unique women. Differences in screening outcomes between each DBT year and the DM year, as well as between groups of women with only 1, 2, or 3 DBT screenings, were assessed, and the odds of recall adjusted for age, race/ethnicity, breast density, and prior mammograms were estimated. Data analysis was performed between February 16 and October 26, 2015. EXPOSURE: Digital mammography screening supplemented with DBT. MAIN OUTCOMES AND MEASURES: Recall rates, cancer cases per recalled patients, and biopsy and interval cancer rates were determined. RESULTS: Screening outcome metrics were evaluated for a total of 44 468 examinations attributable to 23 958 unique women (mean [SD] age, 56.8 [11.0] years) over a 4 year period: year 0 cohort (DM0), 10 728 women; year 1 cohort (DBT1), 11 007; year 2 cohort (DBT2), 11 157; and year 3 cohort (DBT3), 11 576. Recall rates rose slightly for years 1 to 3 of DBT (88, 90, and 92 per 1000 screened, respectively) but remained significantly reduced compared with the DM0 rate of 104 per 1000 screened. Reported as odds ratios (95% CIs), the findings were DM vs DBT1, 0.83 (0.76-0.91, P < .001); DM vs DBT2, 0.85 (0.78-0.93, P < .001); and DM vs DBT3, 0.87 (0.80-0.95, P = .003). The cancer cases per recalled patients continued to rise from DM0 rate of 4.4% to 6.2% (P = .06), 6.5% (P = .03), and 6.7% (P = .02) for years 1 to 3 of DBT, respectively. Outcomes assessed for the most recent screening for individual women undergoing only 1, 2, or 3 DBT screenings during the study period demonstrated decreasing recall rates of 130, 78, and 59 per 1000 screened, respectively (P < .001). Interval cancer rates, determined using available follow-up data, decreased from 0.7 per 1000 women screened with the use of DM to 0.5 per 1000 screened with the use of DBT1. CONCLUSIONS AND RELEVANCE: Digital breast tomosynthesis screening outcomes are sustainable, with significant recall reduction, increasing cancer cases per recalled patients, and a decline in interval cancers. PMID- 26893204 TI - L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade. AB - Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 MUM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade. PMID- 26893206 TI - Prevalence and risk factors of anemia in children. AB - OBJECTIVE: To identify the prevalence and factors associated with anemia in children attending Municipal Early Childhood Education Day Care Center (Centros Municipais de Educacao Infantil [CMEI]) nurseries in Colombo-PR. METHODS: Analytical, cross-sectional study with a representative sample of 334 children obtained by stratified cluster sampling, with random selection of 26 nurseries. Data collection was conducted through interviews with parents, assessment of iron intake by direct food weighing, and hemoglobin measurement using the finger-stick test. Bivariate association tests were performed followed by multiple logistic regression adjustment. RESULTS: The prevalence of anemia was 34.7%. Factors associated with anemia were: maternal age younger than 28 years old (p=0.03), male children (p=0.02), children younger than 24 months (p=0.01), and children who did not consume iron food sources (meat+beans+dark green leafy vegetables) (p=0.02). There was no association between anemia and iron food intake in CMEI. However, iron intake was well below the recommended levels according to the National Education Development Fund resolution, higher prevalence of anemia was observed in children whose intake of iron, heme iron, and nonheme iron was below the median. CONCLUSIONS: In terms of public health, the prevalence of anemia is characterized as a moderate problem in the studied population and demonstrates the need for coordination of interdisciplinary actions for its reduction in CMEI nurseries. PMID- 26893207 TI - Fat mass index performs best in monitoring management of obesity in prepubertal children. AB - OBJECTIVE: An early and accurate recognition of success in treating obesity may increase the compliance of obese children and their families to intervention programs. This observational, prospective study aimed to evaluate the ability and the time to detect a significant reduction of adiposity estimated by body mass index (BMI), percentage of fat mass (%FM), and fat mass index (FMI) during weight management in prepubertal obese children. METHODS: In a cohort of 60 prepubertal obese children aged 3-9 years included in an outpatient weight management program, BMI, %FM, and FMI were monitored monthly; the last two measurements were assessed using air displacement plethysmography. The outcome measures were the reduction of >5% of each indicator and the time to achieve it. RESULTS: The rate of detection of the outcome was 33.3% (95% CI: 25.9-41.6) using BMI, significantly lower (p<0.001) than either 63.3% using %FM (95% CI: 50.6-74.8) or 70.0% (95% CI: 57.5-80.1) using FMI. The median time to detect the outcome was 71 days using FMI, shorter than 88 days using %FM, and similar to 70 days using BMI. The agreement between the outcome detected by FMI and by %FM was high (kappa 0.701), but very low between the success detected by BMI and either FMI (kappa 0.231) or %FM (kappa 0.125). CONCLUSIONS: FMI achieved the best combination of ability and swiftness to identify reduction of adiposity during monitoring of weight management in prepubertal obese children. PMID- 26893208 TI - Impact of health professional training in breastfeeding on their knowledge, skills, and hospital practices: a systematic review. AB - OBJECTIVE: To identify the impact of training in breastfeeding on knowledge, skills, and professional and hospital practices. DATA SOURCE: The systematic review search was carried out through the MEDLINE, Scopus, and LILACS databases. Reviews, studies with qualitative methodology, those without control group, those conducted in primary care, with specific populations, studies that had a belief and/or professional attitude as outcome, or those with focus on the post discharge period were excluded. There was no limitation of period or language. The quality of the studies was assessed by the adapted criteria of Downs and Black. SUMMARY OF DATA: The literature search identified 276 articles, of which 37 were selected for reading, 26 were excluded, and six were included through reference search. In total, 17 intervention articles were included, three of them with good internal validity. The studies were performed between 1992 and 2010 in countries from five continents; four of them were conducted in Brazil. The training target populations were nursing practitioners, doctors, midwives, and home visitors. Many kinds of training courses were applied. Five interventions employed the theoretical and practical training of the Baby-Friendly Hospital Initiative. All kinds of training courses showed at least one positive result on knowledge, skills, and/or professional/hospital practices, most of them with statistical significance. CONCLUSIONS: Training of hospital health professionals has been effective in improving knowledge, skills, and practices. PMID- 26893209 TI - Evaluation of a neonatal screening program for sickle-cell disease. AB - OBJECTIVE: Evaluate the Neonatal Screening Program of the Health Secretariat of the State of Santa Catarina for sickle-cell disease, from January 2003 to December 2012, regarding program coverage and disease frequency. METHODS: Descriptive, observational, cross-sectional study with retrospective data collection. The variables analyzed were: number of live births in the State of Santa Catarina; number of screened children; number of children diagnosed with sickle-cell trait and sickle-cell disease; type of sickle-cell disease diagnosed; age at the time of sample collection, ethnicity/skin color, gender, and origin of children with sickle-cell disease. Descriptive measures and frequency tables were used for data analysis. RESULTS: During the study period, there were 848,833 live births and 730,412 samples were screened by the program, resulting in a coverage of 86.0%. There were 6173 samples positive for sickle-cell trait and 39 for sickle-cell disease. Among children with sickle-cell disease, the median age at the time of sample collection was 6 days. Regarding the ethnicity/skin color, 25 (64.1%) children were white, seven were black, and seven others were not specified. The Midwest and the Highland (Planalto Serrano) of Santa Catarina were the regions with the highest incidence of sickle-cell disease. CONCLUSION: Coverage by the Neonatal Screening Program of Santa Catarina is good, but did not demonstrate an improvement trend over the years. The frequency of sickle-cell disease is low and lower than in the North, Northeast, and Midwest regions. The median age in days at the time of collection is older than the age recommended by the Ministry of Health. PMID- 26893211 TI - Do recombinant-engineered nanoparticle vaccines hold promise for the prevention of respiratory syncytial virus? PMID- 26893210 TI - Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide. AB - OBJECTIVE: To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. METHODS: Case series study with the intravenous administration of gastrin releasing peptide in the dose of 160pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. RESULTS: The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. CONCLUSIONS: This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism. PMID- 26893212 TI - Headache as an Aura of Epilepsy: Video-EEG Monitoring Study. AB - BACKGROUND: Headache can be associated with epilepsy as a pre-ictal, ictal, or post-ictal phenomenon; however, studies of patients with headache as an epileptic aura are scarce. We performed the present study to investigate the incidence and characteristics of headache as an epileptic aura, via confirmation of electroencephalography (EEG) changes by video-EEG monitoring. METHODS: Data of aura and clinical seizure episodes of 831 consecutive patients who undertook video-EEG monitoring were analyzed retrospectively. For patients who had headache as an aura, information on the detailed features of headache was acquired, including location, nature, duration, and the presence of accompanying symptoms. Video-recorded clinical seizures, EEG findings, and neuroimaging data were used to determine the ictal onset areas in the patients. RESULTS: Six out of 831 (0.7%) patients experienced headache as aura (age range, 25-52 years), all of whom had partial seizures. The incidence of pre-ictal headache was 6.3% (25/831), and post-ictal headache was 30.9% (257/831). In patients with headache as aura, five patients described headache as the most frequent aura, and headache was the second most frequent aura in one patient. The characteristics of headache were hemicrania epileptica in two patients, tension-type headache in another two patients, and migraine-like headache in the remaining two patients. No patient met the diagnostic criteria of ictal epileptic headache or migraine aura triggered seizure. CONCLUSION: Our study showed that headache as an aura is uncommon in adult patients with epilepsy, and that headache can present as diverse features, including hemicrania epileptica, tension-type headache, and migraine-like headache. Further studies are necessary to characterize the features of headache as an epileptic aura in adult patients with epilepsy. PMID- 26893213 TI - Comparison of long-labeled pseudo-continuous arterial spin labeling (ASL) features between young and elderly adults: special reference to parameter selection. AB - BACKGROUND: The signal intensity obtained by arterial spin labeling (ASL) depends not only on perfusion signal, but also on arterial transit time (ATT). Although ATT has a more significant effect on accurate regional cerebral blood flow (CBF) calculations, the multiple post-labeling delay (PLD) approach is difficult to use in routine examinations. PURPOSE: To optimize imaging parameters for labeling duration (LD) and PLD and to confirm their validity in long-labeled pseudo continuous ASL. MATERIAL AND METHODS: The perfusion signal was simulated in four LDs and theoretical signal-to-noise ratio efficiency (SNReff) was calculated. In vivo studies were performed on a 3.0 T magnetic resonance imaging (MRI) scanner and 15 volunteers were categorized into either the young or elderly adult groups. We compared the differences in CBF values with or without ATT correction. RESULTS: Regarding signal simulation, perfusion signal increased with the length of LD. SNReff also improved with LD, but SNReff plateaued at an LD of 3.0 s. As for the in vivo study, SNR linearly increased along with the LD. The CBF differences with the correction of ATT were larger in the elderly adult group. This trend was most prominent in the longer ATT area in the occipital cortical region. CONCLUSION: A combination of imaging settings of LD = 3.5 s and PLD = 2.0 s were suggested as optimal imaging parameters for allowing acceptable CBF quantification and sufficient SNR in both young and elderly individuals. PMID- 26893214 TI - In vivo diffusion tensor imaging of chronic spinal cord compression : a rat model with special attention to the conus medullaris. AB - Background Few studies have focused on diffusion tensor imaging (DTI) parameters of the conus medullaris after chronic compression in the cervical spinal cord. Purpose To discuss the correlation of DTI parameters between the chronically compressed cervical spinal cord and the conus medullaris in a rat model at different time points. Material and Methods Fifty female Sprague-Dawley rats were randomized into five groups: control group (group A), sham group (group B), and test groups C, D, and E (1, 2, and 3 weeks after compression, respectively). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the cervical spinal cord and conus medullaris were compared among different groups. Correlations of ADC and FA values of the cervical spinal cord with those of the conus medullaris were performed in all groups. Results The ADC values at the cervical spinal cord and conus medullaris in all test groups were higher than those of group A and B, while the FA values were lower. The ADC value of the cervical spinal cord was linearly correlated with that of the conus medullaris only in group D. There were no linear correlations of FA values between the cervical spinal cord and the conus medullaris in all test groups. Conclusion After compression of the cervical spinal cord, ADC values of the cervical spinal cord and conus medullaris in test group were significantly increased, while FA values were significantly decreased. The ADC value of the cervical spinal cord was linearly correlated with that of the conus medullaris at 2 weeks after compression. PMID- 26893215 TI - A multiple imputation approach for MNAR mechanisms compatible with Heckman's model. AB - Standard implementations of multiple imputation (MI) approaches provide unbiased inferences based on an assumption of underlying missing at random (MAR) mechanisms. However, in the presence of missing data generated by missing not at random (MNAR) mechanisms, MI is not satisfactory. Originating in an econometric statistical context, Heckman's model, also called the sample selection method, deals with selected samples using two joined linear equations, termed the selection equation and the outcome equation. It has been successfully applied to MNAR outcomes. Nevertheless, such a method only addresses missing outcomes, and this is a strong limitation in clinical epidemiology settings, where covariates are also often missing. We propose to extend the validity of MI to some MNAR mechanisms through the use of the Heckman's model as imputation model and a two step estimation process. This approach will provide a solution that can be used in an MI by chained equation framework to impute missing (either outcomes or covariates) data resulting either from a MAR or an MNAR mechanism when the MNAR mechanism is compatible with a Heckman's model. The approach is illustrated on a real dataset from a randomised trial in patients with seasonal influenza. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26893216 TI - Urological complications following kidney transplantation in pediatric age: A single-center experience. AB - Surgical complications during kidney transplantation can seriously affect renal outcomes. We assess occurrence, risk factors, and results of all urological complications in a series of renal transplants in a single center. Children who underwent renal transplant between January 2008 and December 2014 were retrospectively evaluated. Postoperative urological complications were reviewed. Demographic details, cause of ESRD, donor type, and surgical procedures at transplant were analyzed. For statistical analysis, the chi-square test or Fisher's exact test were used as appropriate. One hundred and twenty-one kidney transplants were performed in 117 children (median age 12 yr). Sixty-two of 121 (53%) had an underlying urological malformation. At a median follow-up of three yr, 28 urological complications were recorded (23%): 12 lymphocele (10%), 10 ureteral obstruction (8%), three urinary leakage (2.5%), two symptomatic VUR (1.7%), and one hydropyonephrosis. When lymphocele was excluded, the complication incidence rate dropped to 13%. Ureteral obstruction mostly occurred late after transplant (more than six months). Presence of urological malformation was the only factor related to increased occurrence of urological complication (p = 0.007) and, in particular, ureteral obstruction (p = 0.018). Children with urological malformations presented a statistically significant risk of developing urological complications after kidney transplantation, ureteral obstruction being the most common complication. PMID- 26893217 TI - Progressive Transformation between Two Magnetic Ground States for One Crystal Structure of a Chiral Molecular Magnet. AB - We report the exceptional observation of two different magnetic ground states (MGS), spin glass (SG, T(B) = 7 K) and ferrimagnet (FI, T(C) = 18 K), for one crystal structure of [{Mn(II)(D/L-NH2ala)}3{Mn(III)(CN)6}].3H2O obtained from [Mn(CN)6](3-) and D/L-aminoalanine, in contrast to one MGS for [{Mn(II)(L NH2ala)}3{Cr(III)(CN)6}].3H2O. They consist of three Mn(NH2ala) helical chains bridged by M(III)(CN)6 to give the framework with disordered water molecules in channels and between the M(III)(CN)6. Both MGS are characterized by a negative Weiss constant, bifurcation in ZFC-FC magnetizations, blocking of the moments, both components of the ac susceptibilities, and hysteresis. They differ in the critical temperatures, absolute magnetization for 5 Oe FC (lack of spontaneous magnetization for the SG), and the shapes of the hysteresis and coercive fields. While isotropic pressure increases both T(crit) and the magnetizations linearly and reversibly in each case, dehydration progressively transforms the FI into the SG as followed by concerted in situ magnetic measurements and single-crystal diffraction. The relative strengths of the two moderate Mn(III)-CN-Mn(II) antiferromagnetic (J1 and J2), the weak Mn(II)-OCO-Mn(II) (J3), and Dzyaloshinkii Moriya antisymmetric (DM) interactions generate the two sets of characters. Examination of the bond lengths and angles for several crystals and their corresponding magnetic properties reveals a correlation between the distortion of Mn(III)(CN)6 and the MGS. SG is favored by higher magnetic anisotropy by less distorted Mn(III)(CN)6 in good accordance with the Mn-Cr system. This conclusion is also born out of the magnetization measurements on orientated single crystals with fields parallel and perpendicular to the unique c axis of the hexagonal space group. PMID- 26893218 TI - The Population Pharmacokinetics of D-beta-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate. AB - The administration of ketones to induce a mild ketosis is of interest for the alleviation of symptoms associated with various neurological disorders. This study aimed to understand the pharmacokinetics (PK) of D-beta-hydroxybutyrate (BHB) and quantify the sources of variability following a dose of (R)-3 hydroxybutyl (R)-3-hydroxybutyrate (ketone monoester). Healthy volunteers (n = 37) were given a single drink of the ketone monoester, following which, 833 blood BHB concentrations were measured. Two formulations and five dose levels of ketone monoester were used. A nonlinear mixed effect modelling approach was used to develop a population PK model. A one compartment disposition model with negative feedback effect on endogenous BHB production provided the best description of the data. Absorption was best described by two consecutive first-order inputs and elimination by dual processes involving first-order (CL = 10.9 L/h) and capacity limited elimination (V max = 4520 mg/h). Covariates identified were formulation (on relative oral bioavailable fraction and absorption rate constant) and dose (on relative oral bioavailable fraction). Lean body weight (on first-order clearance) and sex (on apparent volume of distribution) were also significant covariates. The PK of BHB is complicated by complex absorption process, endogenous production and nonlinear elimination. Formulation and dose appear to strongly influence the kinetic profile following ketone monoester administration. Further work is needed to quantify mechanisms of absorption and elimination of ketones for therapeutic use in the form of ketone monoester. PMID- 26893219 TI - Re-dislocation after revision total hip arthroplasty for recurrent dislocation: a multicentre study. AB - PURPOSE: Although most case of dislocations after total hip arthroplasty (THA) can be managed with conservative treatment, recurrent dislocation may require surgical intervention. This multicentre study was conducted to evaluate the re dislocation rate after revision THA for recurrent dislocation, and to determine the risk factors for re-dislocation. METHODS: We retrospectively reviewed the 88 hips in 88 patients who underwent revision THA for recurrent dislocation at five institutions between 1995 and 2014. The mean patient age at surgery was 68.5 years and the mean follow-up period was 53.1 months. Multivariate logistic regression was performed to identify risk factors for re-dislocation. RESULTS: Sixteen hips in 16 patients (18.2 %) re-dislocated at a mean of 25.5 months (range, 1-83 months) after revision THA. Multivariate analysis identified osteonecrosis of the femoral head (odds ratio [OR] = 5.62 vs. osteoarthritis) and a femoral head size < 32 mm (OR = 3.86) as independent risk factors for re dislocation. Eight hips required additional revision THA for re-dislocation. CONCLUSION: The re-dislocation rate after revision THA for recurrent dislocation remains high, suggesting the need for prevention measures. We recommend the use of a femoral head size >= 32 mm. PMID- 26893221 TI - Use of a Magnetic Tracer for Sentinel Lymph Node Detection in Early-Stage Breast Cancer Patients: A Meta-analysis. AB - BACKGROUND: Sentinel lymph node (SLN) dissection involves lymphatic mapping and selective removal of clinically negative lymph nodes at highest risk for harboring metastases. Lymphatic mapping is most often performed using radioisotope with or without blue dye (standard tracers). Sienna+((r)), a superparamagnetic iron oxide that can be detected using the Sentimag((r)) magnetometer, is an alternative mapping agent to identify SLNs that has been investigated in five clinical trials. This meta-analysis was performed to determine if Sienna+((r)) is non-inferior for SLN detection when compared to standard tracers. METHODS: Five clinical trials comparing Sienna+((r)) to a standard technique were identified, and data from these studies were used to determine the agreement by Kappa statistic between Sienna+((r)) and standard tracers in identifying SLNs and malignant SLNs. The trials included 1683 SLNs identified in 804 patients. Data from the studies were imbalanced, therefore additional agreement indices were utilized to compare techniques. The estimated difference between the techniques was analyzed and a margin of <=5 % was used to determine non-inferiority. RESULTS: Agreement between the Sienna+((r)) and standard tracers was strong for SLN detection by patient [prevalence-adjusted bias-adjusted kappa (PABAK) 0.94, 95 % confidence interval (CI) 0.89-0.98], moderate to substantial for SLN detection by node (PABAK 0.68, 95 % CI 0.54 0.82), and strong for the detection of malignant SLNs by patient (PABAK 0.89, 95 % CI 0.84-0.95). Sienna+((r)) demonstrated non-inferiority compared with standard tracers. CONCLUSIONS: The Sienna+((r)) mapping agent is non-inferior to the standard method for SLN detection in patients with clinically node-negative breast cancer. PMID- 26893220 TI - Imported Plasmodium vivax malaria with severe thrombocytopaenia: can it be severe malaria or not? AB - BACKGROUND: Thrombocytopaenia is the most frequent malaria-associated haematologic alteration observed with all five Plasmodium parasites causing disease in humans. Although not included in the World Health Organization criteria for severe Plasmodium falciparum malaria, severe thrombocytopaenia has been increasingly mentioned as an indicator of P. vivax malaria severity. CASE: Here, it is described a case of imported P. vivax malaria in a 37-year old man from Pakistan who presented with severe thrombocytopaenia (5 * 10(9)/L). He was admitted to the intensive care unit and initially treated with a 1-day course of intravenous quinine followed by oral chloroquine and primaquine. The patient's platelet count increased as early as 4 hours after treatment inception and the clinical course was favourable and uneventful. DISCUSSION: This case report, along with a review of published cases focusing on the relationship between thrombocytopaenia and severe P. vivax malaria, suggests that the prognostic role of severe thrombocytopaenia is ambiguous in absence of severe haemorraghic complications and its use as diagnostic criterion of malaria severity may lead to overestimation of severe P. vivax malaria cases. CONCLUSION: Due to the lack of high quality studies it is at present unclear if severe thrombocytopaenia in the setting of P. vivax malaria should be considered indicative of severe malaria. PMID- 26893223 TI - A New Technology for Sentinel Node Biopsy: A Logistic Improvement. PMID- 26893222 TI - Pancreatectomy with Mesenteric and Portal Vein Resection for Borderline Resectable Pancreatic Cancer: Multicenter Study of 406 Patients. AB - PURPOSE: The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role. METHODS: A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis. RESULTS: Complications occurred in 51.9 % of patients and postoperative death in 7.1 %. Histological invasion of the resected vein was confirmed in 56.7 % of specimens. Five-year survival was 24.4 % with median survival of 24 months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy. CONCLUSIONS: This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols. PMID- 26893224 TI - Women in medical physics: a preliminary analysis of workforce and research participation in Australia and New Zealand. AB - Although the participation of women within the science, technology, engineering and mathematics workforces has been widely discussed over recent decades, the recording and analysis of data pertaining to the gender balance of medical physicists in Australia and New Zealand remains rare. This study aimed to provide a baseline for evaluating future changes in workforce demographics by quantifying the current level of representation of women in the Australasian medical physics workforce and providing an indication of the relative contribution made by those women to the local research environment. The 2015 Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) member directory and list of chief physicists at ACPSEM-accredited radiation oncology and diagnostic imaging training centres were interrogated to identify the gender balance of medical physicists working in Australia and New Zealand. A specific investigation of the employment levels of all medical physicists in Queensland was undertaken to provide an example of the gender balance at different levels of seniority in one large Australian state. Lists of authors of medical physics presentations at ACPSEM annual conferences and authors of publications in the ACPSEM's official journal, were used to provide an indication of the gender balance in published research within Australia and New Zealand. The results of this study showed that women currently constitute approximately 28 % of the medical physics workforce in Australia and New Zealand, distributed disproportionally in junior roles; there is a decrease in female participation in the field with increasing levels of seniority, which is particularly apparent in the stratified data obtained for the Queensland workforce. Comparisons with older data suggest that this situation has changed little since 2008. Examination of ACPSEM conference presentations suggested that there are similar disparities between the gender-balance of proffered and invited or keynote speakers (28 % and 13 % from female authors) and the gender balance of certified and chief physicists (28 % and 21 % female). The representation of women in the ACPSEM journal does not differ substantially between authorship of proffered versus invited work (22 % and 19 % from female authors). While this work was limited to evaluating the membership, annual conference and official journal of the ACPSEM (rather than evaluating the entire medical physics workforce and the contributions of male and female physicists to international conferences and publications), this study nonetheless led to the following recommendations: that a longitudinal study analysing correlations between age, period of service, seniority and gender should be undertaken and that future ACPSEM workforce surveys should include analyses of gender representation. PMID- 26893225 TI - Stability Comparison of Perovskite Solar Cells Based on Zinc Oxide and Titania on Polymer Substrates. AB - Device scale-up and long-term stability constitute two major hurdles that the emerging perovskite solar technology will have to overcome before commercialization. Here, a comparative study was performed between ZnO and TiO2 electron-selective layers, two materials that allow the low-temperature processing of perovskite solar cells on polymer substrates. Although the use of TiO2 is well established on glass substrates, ZnO was chosen because it can be readily printed at low temperature and offers the potential for the large-scale roll-to-roll manufacturing of flexible photovoltaics at a low cost. However, a rapid degradation of CH3 NH3 PbI3 was observed if it was deposited on ZnO, therefore, the influence of the perovskite film preparation conditions on its morphology and degradation kinetics was investigated. This study showed that CH3 NH3 PbI3 could withstand a higher temperature on TiO2 than ZnO and that TiO2 based perovskite devices were more stable than their ZnO analogues. PMID- 26893226 TI - Computational hemodynamics of abdominal aortic aneurysms: Three-dimensional ultrasound versus computed tomography. AB - The current criterion for surgical intervention in abdominal aortic aneurysms, based upon a maximal aortic diameter, is considered conservative due to the high mortality rate in case of rupture. The research community is actively investigating the use of computational mechanics tools combined with patient specific imaging to help identify more accurate criteria. Widespread uptake of a successful metric will however be limited by the need for computed tomography, which is at present the primary image extraction method on account of the location and complex shape of the aneurysms. The use of three-dimensional ultrasound as the scanning method is more attractive on account of increased availability, reduced cost and reduced risk to patients. The suitability of three dimensional ultrasound is assessed for this purpose in the present work; computational fluid dynamics simulations were performed on geometries obtained from the same patient using both ultrasound and computed tomography. The influence of different smoothing algorithms is investigated in the geometry preparation stage and Taubin's low-pass filter was found to best preserve geometry features. Laminar, Newtonian, steady-state simulation analysis identified haemodynamic characteristics to be qualitatively similar in terms of wall shear stress, velocity and vorticity. The study demonstrates the potential for three-dimensional ultrasound to be integrated into a more accessible patient specific modelling tool able to identify the need for surgical intervention of abdominal aortic aneurysms. PMID- 26893227 TI - Video tracking for high-similarity drug tablets based on reflective lightness intensity and fuzzy recognition system. AB - Video tracking of drug tablet exerts important influences on the efficiency and reliability of its mass production; this topic also becomes a difficult and targeted focus for pharmaceutical production monitory in the past several years due to the high similarity and random distribution of those objectives to be searched for. By measuring the reflective lightness intensity of illumination lightness on tablet surface, reflective lightness intensity matrix was established and demonstrated in the form of grey image, presenting its shape topology and topography details in return. On this basis, a series of mathematical properties for describing reflective lightness intensity images were proposed, thereafter a set of fuzzy recognition system and its identification rules can be employed to classify those moving tablets with inputted image properties, which facilitates the determination of their instantaneous coordinate positions on given image frame accordingly. By repeating identical operations on the next frame, the real-time motions of tablet objectives were traced successfully. Orthogonal tracking experiment and performance comparisons verified the accuracy and reliability of this new method in pharmaceutical industry. With original suggestions concerning imaging arrangements, tablet descriptions and video tracking, this article provides reliable references and new research ideas for tablet tracking performance in high-yielding production domain. PMID- 26893228 TI - Inclusion of the periodontal ligament in studies on the biomechanical behavior of fiber post-retained restorations: An in vitro study and three-dimensional finite element analysis. AB - Endodontically treated teeth are known to have reduced structural strength. Periodontal ligament may influence fracture resistance. The purpose of this study was to assess the influence of including the periodontal ligament in biomechanical studies about endodontically treated and restored teeth. Forty human maxillary central incisors were treated endodontically and randomly divided into four groups: non-crowned (with and without an artificial ligament) and crowned (with and without an artificial ligament) with glass-ceramic crowns. All groups received prefabricated glass-fiber posts and a composite resin core. Specimens were tested, under a flexural-compressive load, until failure occurred. The failure mode was registered for all specimens. The failure loads were recorded and analyzed using an analysis of variance test (p < 0.05). These results were compared with those predicted by a finite element model. The analysis of variance did not show significant differences between the use of crown on the failure load (p = 0.331) and the use of periodontal ligament (p = 0.185). A cohesive mode in crown appeared in crowned teeth and in core in non crowned groups. For non-crowned teeth, adhesive failure occurred along the cement enamel junction with a slight tendency in specimens without periodontal ligament. Furthermore, an unfavorable failure mode affects partially the root with no differences regarding non-crown specimens. In crowned teeth, the tendency was an adhesive failure along the cement-enamel junction. The model predicted a distribution of the safety factor consistent with these results. This study showed that inclusion of periodontal ligament is not particularly important on biomechanical behavior of post-retained restorations. However, we recommend its inclusion in fatigue studies. PMID- 26893229 TI - Novel movement disorder society-Parkinson's disease criteria: What about SWEDD and genetic forms? PMID- 26893230 TI - The role of drought- and disturbance-mediated competition in shaping community responses to varied environments. AB - By altering the strength of intra- and interspecific competition, droughts may reshape plant communities. Furthermore, species may respond differently to drought when other influences, such as herbivory, are considered. To explore this relationship, we conducted a greenhouse experiment measuring responses to inter- and intraspecific competition for two grasses, Schedonorus arundinaceus and Paspalum dilatatum, while varying water availability and simulating herbivory via clipping. We then parameterized population growth models to examine the long-term outcome of competition under these conditions. Under drought, S. arundinaceus was less water stressed than P. dilatatum, which exhibited severe water stress; clipping alleviated this stress, increasing the competitive ability of P. dilatatum relative to S. arundinaceus. Although P. dilatatum competed weakly under drought, clipping reduced water stress in P. dilatatum, thereby enhancing its ability to compete with S. arundinaceus under drought. Supporting these observations, population growth models predicted that P. dilatatum would exclude S. arundinaceus when clipped under drought, while S. arundinaceus would exclude P. dilatatum when unclipped under drought. When the modeled environment varied temporally, environmental variation promoted niche differences that, though insufficient to maintain stable coexistence, prevented unconditional competitive exclusion by promoting priority effects. Our results suggest that it is important to consider how species respond not just to stable, but also to variable, environments. When species differ in their responses to drought, competition, and simulated herbivory, stable environments may promote competitive exclusion, while fluctuating environments may promote coexistence. These interactions are critical to understanding how species will respond to global change. PMID- 26893231 TI - Comorbidity of Personality Disorders and Adult Attention Deficit Hyperactivity Disorder (ADHD)--Review of Recent Findings. AB - Children suffering from attention deficit hyperactivity disorder (ADHD) may remit until adulthood. But, more than 60-80% have persisting ADHD symptoms. ADHD as an early manifesting neurodevelopmental disorder is considered a major risk factor for the development of comorbid psychiatric disorders in later life. Particularly, personality disorders are oftentimes observed in adult patients suffering from ADHD. If ADHD and personality disorders share common etiological mechanisms and/or if ADHD as a severely impairing condition influences psychological functioning and learning and leads to unfavorable learning histories is unclear. The development of inflexible and dysfunctional beliefs on the basis of real and perceived impairments or otherness due to the core symptoms of ADHD is intuitively plausible. Such beliefs are a known cause for the development of personality disorders. But, why some personality disorders are more frequently found in ADHD patients as for example antisocial and borderline personality disorder remains subject of debate. Because of the high prevalence of ADHD and the high impact of personality disorders on daily functioning, it is important to take them into account when treating patients with ADHD. Research on the developmental trajectories leading to personality disorders in adult ADHD patients might open the door for targeted interventions to prevent impairing comorbid clinical pictures. PMID- 26893232 TI - Elderly Sexual Offenders. AB - With the ever-aging population, the number of elderly sexual offenders are also on the rise. The courts and correctional system are increasingly faced with older individuals who have offended sexually. Previously, these older offenders were thought to be similar to younger sexual offenders. However, closer analysis suggests that many of these individuals pose a much lower risk to recidivate than the risk to recidivate of their younger counterparts. Still, an individualized approach to manage the risk of older offenders is required, as some may have particular risk factors relevant for their treatment and future stability, such as dementia or other mental health issues. Further, this population often has particular physical health issues and requires special consideration when being placed in the community. Assessment, treatment, and risk management in this special population of sexual offenders are discussed. PMID- 26893233 TI - Is There a Bipolar Prodrome Among Children and Adolescents? AB - Bipolar disorder in youth substantially impairs behavior, family, and social functioning and interferes with developmental course. There is increasing interest in defining a bipolar prodrome similar to that reported in early-onset psychosis that will allow for earlier intervention and reduction in overall morbidity and mortality. Several lines of research have addressed this important issue including studies of offspring of bipolar parents, high-risk cohorts, and longitudinal follow-up of subjects with major depressive disorder (MDD), ADHD, and bipolar spectrum disorder. The development and validation of bipolar prodrome rating scales also shows promise. Recent attempts to intervene at earlier stages of bipolar disorder have led to some positive outcomes. However, a controversy remains concerning the identification and management of the earliest symptoms. Further research is needed to fully validate a bipolar prodrome and to determine the optimal course of action at various stages of illness. PMID- 26893234 TI - Treatment Protocols for Eating Disorders: Clinicians' Attitudes, Concerns, Adherence and Difficulties Delivering Evidence-Based Psychological Interventions. AB - There are several protocols in existence that guide clinicians in the implementation of effective, evidence-based psychological interventions for eating disorders. These have been made accessible in the form of treatment manuals. However, relatively few clinicians use those protocols, preferring to offer more eclectic or integrative approaches. Following a summary of the research that shows that these evidence-based approaches can be used successfully in routine clinical settings, this review considers why there is such poor uptake of these therapies in such settings. This review focuses on the role of service culture and on clinicians' own attitudes, beliefs and emotions. Possible means of enhancing uptake are considered, but these cannot be considered to be ideal solutions at present. PMID- 26893235 TI - Ecological Momentary Assessment in Eating Disorder and Obesity Research: a Review of the Recent Literature. AB - Our current understanding of the etiology and maintenance of eating disorders and obesity continues to be far from complete. Similarly, our understanding of determinants of both successful and unsuccessful weight loss surgery is also quite limited. While a number of research methodologies have been applied to these areas, one methodology that has recently seen a rise in popularity is the use of ecological momentary assessment (EMA). EMA allows one to study a variety of variables of interest in the natural environment. The study of eating disorders, obesity, and bariatric surgery has all been conducted using EMA recently. The current study is a review of these areas and summarizes the recent literature (past 3 years) in eating disorders, obesity, and bariatric surgery using EMA methodology. PMID- 26893237 TI - Posttraumatic growth in breast cancer survivors: does age matter? AB - OBJECTIVE: Many women report positive life changes, or posttraumatic growth (PTG), as a result of their experience with breast cancer. However, despite compelling evidence that younger age at diagnosis is associated consistently with greater distress, age has not been integrated into models of PTG. Drawing from the theoretical and empirical literature, we tested whether key correlates (i.e., cancer-related impact and engagement, positive mood) of PTG varied by age at breast cancer diagnosis. METHODS: Participants were 175 women with early stage breast cancer followed from completion of primary treatment through one year post treatment. Analyses involved data collected at the one-year assessment. RESULTS: As hypothesized, correlates of PTG varied significantly as a function of age. Perceived negative impact of the cancer experience was associated with growth for older women (p = .046), whereas approach-oriented coping (p = .004), an expansive time perspective (p = .007), and positive mood were associated with growth for younger women (p = .007). CONCLUSIONS: PTG may involve distinct processes for women diagnosed at different ages. Consideration of lifespan developmental processes is necessary when studying positive adjustment to cancer. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26893239 TI - Why do immunology research in hemophilia? PMID- 26893238 TI - Critical role of the C5a-activated neutrophils in high-fat diet-induced vascular inflammation. AB - Exceed and chronic high-fat diet (HFD) contributes to the diagnosis and development of atherosclerosis, obesity, and metabolic syndrome. However, the key molecular component(s) triggered by HFD responsible for initiating vascular inflammation remain unknown. We observed that feeding HFD for 4 weeks is sufficient to induce leukocyte recruitment in the femoral artery of wild-type mice. Neutrophil- and monocyte-depletion analyses confirmed the preferential recruitment of neutrophils in these mice. Protein analysis of sera from HFD-fed mice revealed a marked elevation of complement component C5a levels. Exogenous C5a alone induced leukocyte recruitment, which was abolished by a C5a-receptor antagonist. We also examined the role of neutrophil-derived MCP-1 in accumulation of leukocytes in the artery. These results demonstrated a previously unrecognized role for C5a and neutrophils in the early onset of HFD-induced vascular inflammation. Further study may help in elucidating a novel regulatory pathway to control diet-induced inflammation such as that in case of atherosclerosis. PMID- 26893236 TI - A Review of Scales to Measure Social Anxiety Disorder in Clinical and Epidemiological Studies. AB - To advance research into social anxiety disorder (SAD) and provide efficacious treatments for individuals with SAD, researchers and clinicians must have effective assessment instruments for identifying the disorder in terms of its diagnostic criteria, symptoms, and the presence of specific maintaining factors. This review highlights the main lines of existing adult and youth research on scales that form part of diagnostic instruments that assess SAD, scales that measure social anxiety symptoms, and scales that measure theory-based psychological maintaining factors associated with SAD. The review also highlights methodological issues that impact on the use of the aforementioned scales. The continued refinement and comparative evaluation of measures for SAD, culminating in the ascertainment of optimal measures, will improve the assessment and identification of the disorder. Improved identification of the disorder will contribute to the advancement of SAD research and treatment. PMID- 26893242 TI - Impact of {Os(pap)2} in fine-tuning the binding modes and non-innocent potential of deprotonated 2,2'-bipyridine-3,3'-diol. AB - The reaction of ctc-Os(II)(pap)2Cl2 (pap = 2-phenylazopyridine, ctc = cis-trans cis with respect to chlorides and pyridine/azo nitrogens of pap, respectively) and ambidentate 2,2'-bipyridine-3,3'-diol (H2L) leads to the simultaneous formation of isomeric [Os(II)(pap)2(HL(-))](+) ((2+)/(3+)), seven-membered chelate containing Os(II)(pap)2(L(2-)) (4) and diastereomeric [{Os(II)(pap)2}2(MU L(2-))](2+) (5a(2+) (meso, DeltaLambda)/5b(2+) (rac, DeltaDelta/LambdaLambda)). The reaction of 2,2'-biphenol (H2L') and ctc-Os(II)(pap)2Cl2 yields Os(II)(pap)2(L'(2-)) (6), an analogue of 4. The identities of the newly designed complexes have been established by different analytical, spectroscopic and X-ray diffraction techniques. (1)H-NMR spectra of the complexes and single crystal X ray structures of selective derivatives [2]ClO4, [3]ClO4, [5a](ClO4)2, and 6 establish the retention of the tc-configuration of the precursor {Os(pap)2}. In isomeric 2(+) and 3(+), monodeprotonated HL(-) is linked to the {Os(II)(pap)2} fragment through N,N and N,O(-) donors, resulting in nearly planar five- and six membered chelates with O-HO(-) and O-HN hydrogen bonds at its back face, respectively. The O(-),O(-) donating L'(2-) extends a severely twisted seven membered chelate with the {Os(pap)2} unit in 6. The N,O(-)/O(-),N donors of deprotonated L(2-) bridge the two {Os(II)(pap)2} units in a symmetric fashion in 5a(2+), forming two moderately twisted six-membered chelates. Though the deprotonation of the O-HN hydrogen bond in (+) by another unit of {Os(II)(pap)2} generates a diastereomeric mixture of 5a(2+) and 5b(2+), attempts to deprotonate the relatively stronger O-H...O(-) hydrogen bond in 2(+) have failed. The isomeric 2(+)/3(+), seven-membered chelate containing 4/6 and diastereomeric 5a(2+)/5b(2+) exhibit distinctive (1)H-NMR and absorption spectra as well as electrochemical responses. The pap (N[double bond, length as m-dash]N) based two successive reductions and the participation of HL(-), L(2-), L'(2-) in the oxidation processes of the respective complexes have been revealed using EPR and DFT calculated MOs and Mulliken spin density plots at the intermediate paramagnetic states. PMID- 26893240 TI - Toxicity evaluation of hydroalcoholic extract of Ferula gummosa root. AB - Traditionally, people use harvested Ferula gummosa for medicinal purposes. However, no information about its safety and toxicity is available. In the present study, the toxicological profile of sub-chronic oral administration of hydroalcoholic extract of F. gummosa radix is evaluated in rats. The extract was orally administrated at 100 and 600 mg/kg to male rats for 28 days. After 28 days, clinical signs, mortality, body weights, food and water consumption, organ weights, hematology, serum biochemistry, as well as histopathological and neurobehavioral changes were examined. Also, the sedative effect of this extract was evaluated in mice at the doses of 100, 600, and 800 mg/kg. Its cytotoxicity against human stroma-vascular cells and human renal epithelial cells were also evaluated. No lethality or adverse toxic signs were seen during the experimental period. There were no significant changes in body and organ weights, hematology, serum biochemistry, and histopathological examination. The extract decreased the rotarod performance, but did not increase pentobarbital-induced hypnosis. Also, F. gummosa extract significantly decreased cell viability at the concentrations of higher than 400 MUg/mL. In conclusion, the sub-chronic toxicity study of F. gummosa hydroalcoholic extract demonstrated the extract to be safe for the tested dosage and route of administration. PMID- 26893241 TI - A practical review on carfilzomib in multiple myeloma. AB - Carfilzomib, a second-generation proteasome inhibitor, has been increasingly used in relapsed/refractory multiple myeloma (MM) since its approval by the American food and drug administration (FDA) in the summer of 2012. The drug is active as a single agent and in combination with other antimyeloma agents. As a result of its efficacy and safety in the relapsed/refractory setting, carfilzomib is being evaluated in patients with newly diagnosed MM as well as in high-risk smoldering MM. This review will give a comprehensive summary of the drug, including its mechanism of action, the evaluated doses and schedules as well as a summary of the main clinical trials in the relapsed/refractory and newly diagnosed settings. A focus will be placed upon certain subgroups of interest as well as a description of the toxicity associated with carfilzomib use and a clinical perspective on toxicity management. PMID- 26893244 TI - Enhanced design of inhaled therapeutics: what does the future hold? PMID- 26893243 TI - Third-generation antibody drug conjugates for cancer therapy--a balancing act. PMID- 26893245 TI - The potential of protein-based nanocages for imaging and drug delivery. PMID- 26893246 TI - The physics of drug-delivery across the blood-brain barrier. PMID- 26893247 TI - Nanotechnology and traditional medicine: challenges and opportunities. PMID- 26893248 TI - The immediate effects of lidocaine iontophoresis using interferential current on pressure sense threshold and tactile sensation. AB - Iontophoresis is the noninvasive delivery of ions using direct current. The direct current has some disadvantages such as skin burning. Interferential current is a kind of alternating current without limitations of direct current; so the purpose of this study is to investigate and compare the effects of lidocaine, interferential current and lidocaine iontophoresis using interferential current. 30 healthy women aged 20-24 years participated in this randomized clinical trial study. Pressure, tactile and pain thresholds were evaluated before and after the application of treatment methods. Pressure, tactile and pain sensitivity increased significantly after the application of lidocaine alone (p < 0.005) and lidocaine iontophoresis using interferential current (p < 0.0001). Lidocaine iontophoresis using interferential current can increase perception threshold of pain, tactile stimulus and pressure sense more significantly than lidocaine and interferential current alone. PMID- 26893249 TI - Flow vibration-doubled concentric system coupled with low ratio amine to produce bile acid-macrocapsules of beta-cells. AB - BACKGROUND: Pancreatic beta-cell microencapsulation using sodium alginate (SA), polylornithine (PLO) copolymers, and ultrasoluble hydrogels, polystyrenes and polyallamines (PAA), has been heavily studied. However, long-term success remains limited due to poor macrocapsules' physical properties and cell functions. Our study aimed to incorporate percentages of PAA and ursodeoxycholic acid, into SA and PLO dispersion mixture and examine best microencapsulating methods and best macrocapsules containing beta-cells. METHODS/RESULTS: Microencapsulating parameters were examined and the Flow-Vibrational Nozzle built-in system was screened and found to be most efficient at high frequency (1900 Hz). Macrocapsules were produced with or without ursodeoxycholic acid in percentages: 0.018SA:0.01PLO:0.005PAA:0.04ursodeoxycholic acid (up to 100% H2O). Using the refined microencapsulation method with vibrational frequency of 1900 Hz, macrocapsules with ursodeoxycholic acid had optimized cell viability and biological functions and ameliorated inflammatory biomarkers. CONCLUSION: High frequency and air-pressure with Flow-Vibrational encapsulation using the mixture: 0.018SA:0.01PLO:0.005PAA:0.04ursodeoxycholic acid resulted in better cell biology suggesting potentials in beta-cell transplantation. PMID- 26893250 TI - A review of current and novel levodopa formulations for the treatment of Parkinson's disease. AB - Parkinson's disease treatment is characterized by the nearly inevitable development of motor complications, including fluctuations and dyskinesias, in which the duration of benefit of a dose of medication is offset by involuntary movements that can be more disabling than the Parkinsonian features themselves. While levodopa remains the gold standard of therapy, it is the most likely to be associated with these complications. The concept of continuous dopaminergic stimulation has gained increasing acceptance as a potential mechanism by which to avoid or delay the development of motor complications, or to minimize their impact once they have already occurred. This article will explore existing and novel formulations of levodopa to identify their role in the spectrum of Parkinson's disease therapeutics. PMID- 26893252 TI - Authors' Reply to Ultrasound vs MRI for stroke shoulder: Apples and pears or simply N/A? PMID- 26893251 TI - Cinnamaldehyde supplementation prevents fasting-induced hyperphagia, lipid accumulation, and inflammation in high-fat diet-fed mice. AB - Cinnamaldehyde, a bioactive component of cinnamon, is increasingly gaining interest for its preventive and therapeutic effects against metabolic complications like type-2 diabetes. This study is an attempt to understand the effect of cinnamaldehyde in high-fat diet (HFD)-associated increase in fasting induced hyperphagia and related hormone levels, adipose tissue lipolysis and inflammation, and selected cecal microbial count in mice. Cinnamaldehyde, at 40 uM dose, prevented lipid accumulation and altered gene expression toward lipolytic phenotype in 3T3-L1 preadipocyte cell lines. In vivo, cinnamaldehyde coadministration prevented HFD-induced body weight gain, decreased fasting induced hyperphagia, as well as circulating leptin and leptin/ghrelin ratio. In addition to that, cinnamaldehyde altered serum biochemical parameters related to lipolysis, that is, glycerol and free fatty acid levels. At transcriptional level, cinnamaldehyde increased anorectic gene expression in hypothalamus and lipolytic gene expression in visceral white adipose tissue. Furthermore, cinnamaldehyde also decreased serum IL-1beta and inflammatory gene expression in visceral white adipose tissue. However, cinnamaldehyde did not modulate the population of selected gut microbial (Lactobacillus, Bifidibaceria, and Roseburia) count in cecal content. In conclusion, cinnamaldehyde increased adipose tissue lipolysis, decreased fasting-induced hyperphagia, normalized circulating levels of leptin/ghrelin ratio, and reduced inflammation in HFD-fed mice, which augurs well for its antiobesity role. PMID- 26893253 TI - Drinking Like an Adult? Trajectories of Alcohol Use Patterns Before and After College Graduation. AB - BACKGROUND: College students who engage in high-risk drinking patterns are thought to "mature out" of these patterns as they transition to adult roles. College graduation is an important milestone demarcating this transition. We examine longitudinal changes in quantity and frequency of alcohol consumption between the college years and the 4 years after graduation and explore variation in these changes by gender and race/ethnicity. METHODS: Participants were 1,128 college graduates enrolled in a longitudinal prospective study of health-risk behaviors. Standard measures of alcohol consumption were gathered during 8 annual personal interviews (76 to 91% annual follow-up). Graduation dates were culled from administrative data and self-report. Spline models, in which separate trajectories were modeled before and after the "knot" of college graduation, were fit to 8 annual observations of past-year alcohol use frequency and quantity (typical number of drinks/drinking day). RESULTS: Frequency increased linearly pregraduation, slightly decreased postgraduation, and then rebounded to pregraduation levels. Pregraduation frequency increased more steeply among individuals who drank more heavily at college entry. Quantity decreased linearly during college, followed by quadratic decreases after graduation. CONCLUSIONS: Results suggest that the postcollege "maturing-out" phenomenon might be attributable to decreases in alcohol quantity but not frequency. High-frequency drinking patterns that develop during college appear to persist several years postgraduation. PMID- 26893255 TI - Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents. AB - A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar-phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents. PMID- 26893254 TI - Potential role of AKT/mTOR signalling proteins in hairy cell leukaemia: association with BRAF/ERK activation and clinical outcome. AB - The potential role of AKT/mTOR signalling proteins and its association with the Raf-MEK-ERK pathway was investigated in hairy cell leukaemia (HCL). BRAFV600E expression and activated forms of AKT, mTOR, ERK1/2, p70S6k and 4E-BP1 were immunohistochemically assessed in 77 BM biopsies of HCL patients and correlated with clinicopathological and BM microvascular characteristics, as well as with c Caspase-3 levels in hairy cells. Additionally, we tested rapamycin treatment response of BONNA-12 wild-type cells or transfected with BRAFV600E. Most HCL cases expressed p-p70S6K and p-4E-BP1 but not p-mTOR, being accompanied by p ERK1/2 and p-AKT. AKT/mTOR activation was evident in BONNA-12 cells irrespective of the presence of BRAFV600E mutation and was implicated in cell proliferation enhancement. In multivariate analysis p-AKT/p-mTOR/p-4E-BP1 overexpression was an adverse prognostic factor for time to next treatment conferring earlier relapse. When p-AKT, p-mTOR and p-4E-BP1 were examined separately only p-4E-BP1 remained significant. Our findings indicate that in HCL, critical proteins up- and downstream of mTOR are activated. Moreover, the strong associations with Raf-MEK ERK signalling imply a possible biologic interaction between these pathways. Most importantly, expression of p-4E-BP1 alone or combined with p-AKT and p-mTOR is of prognostic value in patients with HCL. PMID- 26893256 TI - Dietary compound alpha-asarone alleviates ER stress-mediated apoptosis in 7beta hydroxycholesterol-challenged macrophages. AB - SCOPE: Prolonged endoplasmic reticulum (ER) stress has lost the function of protein folding capacity and the ER accumulation of unfolded proteins that eventually triggers apoptosis. Oxysterols are emerging as contributing factors in atherogenesis known to involve macrophage apoptosis. This study determined the inhibitory effect of alpha-asarone present in purple perilla, on 7beta hydroxycholesterol-induced macrophage apoptosis, targeting against ER stress signaling pathway. METHODS AND RESULTS: J774A1 murine macrophages were exposed to 28 MUM 7beta-hydroxycholesterol and treated with 1-10 MUM alpha-asarone. Macrophage apoptosis and ER stress were examined by and alpha-Asarone blocked 7beta-hydroxycholesterol-induced DNA fragmentation and apoptosome formation. Immunoblotting showed that the oxysterol activated the ER transmembrane resident kinases of IRE1alpha, PERK and ATF4 and triggered caspase-12 signaling cascades, which was reversed by alpha-asarone. Additionally, 7beta-hydroxycholesterol activated TRAF2-ASK1-JNK1/2 complex following the IRE1alpha activation, and alpha asarone blunted such IRE1alpha-mediated pathway. Real-time PCR and dual luciferase reporter analyses revealed that alpha-asarone reduced transcriptional activation of ER stress-responsive genes including XBP1 and CHOP by 7beta hydroxycholesterol. Finally, alpha-asarone disturbed oxysterol-elicited signaling of PERK and ATF4 responsible for CHOP induction. CONCLUSION: alpha-Asarone blocked 7beta-hydroxycholesterol-induced macrophage apoptosis through allaying ER stress-specific signaling involving caspase activation and CHOP induction. alpha Asarone was an anti-atherosclerotic agent antagonizing ER stress-mediated macrophage apoptosis by 7beta-hydroxycholesterol. PMID- 26893257 TI - Ophthalmological characteristics in children with Leigh syndrome - A long-term follow-up. AB - PURPOSE: To describe ophthalmological characteristics in children with Leigh syndrome (LS), an inherited, progressive, mitochondrial encephalomyopathy, at diagnosis and over time, and relate the results to causative genetic mutations. METHODS: Forty-four children with LS (19 females), with a median age of 2.4 years (range: 0.6-14.2 years) at diagnosis, were studied at the Queen Silvia Children's Hospital, Gothenburg, Sweden. Twenty-eight children had known genetic defects. The children underwent an ophthalmological examination, including visual acuity (VA), eye motility, refraction, slit lamp examination, ophthalmoscopy and a full field electroretinogram (ff-ERG). Seventeen children were available for follow-up over a mean time of 5.4 years (range: 0.3-14.8 years). The results of these children were compared with an age- and sex-matched reference group of healthy children (n = 119). RESULTS: Altogether 36/44 of the children (82%) had ophthalmological abnormalities. The most common findings were refractive errors (n = 16/25), low VA (n = 9/36), strabismus (n = 8/42), reduced eye motility (n = 8/40), optic atrophy (n = 7/41), retinal pigmentation (n = 6/40) and nystagmus (n = 6/42). Several ophthalmological manifestations appeared over time. In 5/22 children, ff-ERG showed retinal dystrophy. No significant correlation between phenotype and genotype was found. The children with LS had significantly lower VA (p < 0.0001, Mantel-Haenszel chi-square exact test), more astigmatism (p = 0.012, Fisher's exact test) and higher incidence of strabismus (p = 0.0002) compared to controls at follow-up. CONCLUSIONS: In this unique cohort of children with LS, the vast majority showed ophthalmological findings at diagnosis, which increased over time. Therefore, we recommend that all children diagnosed with LS should be followed up with regular ophthalmological examinations. PMID- 26893259 TI - Altered Striatal Response During Effort-Based Valuation and Motivation in Alcohol Dependent Individuals. AB - AIMS: To use functional magnetic resonance imaging (fMRI) to investigate the neural circuitry behind effort-related valuation and motivation in a population of alcohol-dependent participants and healthy controls. METHODS: Seventeen alcohol-dependent participants and a comparison group of 17 healthy control participants completed an effort-based motivation paradigm during an fMRI scan, in which they were required to exert effort at varying levels in order to earn a monetary reward. RESULTS: We found that alcohol-dependent participants were less motivated during trials requiring high levels of effort. The whole-brain fMRI analysis revealed that alcohol-dependent participants displayed an increased blood-oxygen-level dependent (BOLD) signal during low and unknown effort cues in the dorsal and ventral striatum compared with healthy controls. CONCLUSION: These findings provide the first evidence that alcohol-dependent participants and healthy controls differ in their effort-based valuation and motivation processing. Alcohol-dependent participants displayed a hyperactive mesolimbic reward circuitry recruited by non-drug rewards, potentially reflecting a sensitization to reward in this patient population. PMID- 26893258 TI - Exercise-induced oxidative stress: past, present and future. AB - The existence of free radicals in living cells was first reported in 1954 and this important finding helped launch the field of free radical biology. However, the discovery that muscular exercise is associated with increased biomarkers of oxidative stress did not occur until 1978. Following the initial report that exercise promotes oxidative stress in humans, many studies have confirmed that prolonged or short-duration high intensity exercise results in increased radical production in active skeletal muscles resulting in the formation of oxidized lipids and proteins in the working muscles. Since these early descriptive studies, the investigation of radicals and redox biology related to exercise and skeletal muscle has grown as a discipline and the importance of this research in the biomedical sciences is widely recognized. This review will briefly summarize the history of research in exercise-induced oxidative stress and will discuss the major paradigm shifts that the field has undergone and continues to experience. We conclude with a discussion of future directions in the hope of stimulating additional research in this important field. PMID- 26893261 TI - NAFLD: Unravelling the path to steatohepatitis. PMID- 26893260 TI - Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. AB - Hypophosphatasia is the inborn error of metabolism characterized by low serum alkaline phosphatase activity (hypophosphatasaemia). This biochemical hallmark reflects loss-of-function mutations within the gene that encodes the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a cell-surface homodimeric phosphohydrolase that is richly expressed in the skeleton, liver, kidney and developing teeth. In hypophosphatasia, extracellular accumulation of TNSALP natural substrates includes inorganic pyrophosphate, an inhibitor of mineralization, which explains the dento-osseous and arthritic complications featuring tooth loss, rickets or osteomalacia, and calcific arthopathies. Severely affected infants sometimes also have hypercalcaemia and hyperphosphataemia due to the blocked entry of minerals into the skeleton, and pyridoxine-dependent seizures from insufficient extracellular hydrolysis of pyridoxal 5'-phosphate, the major circulating form of vitamin B6, required for neurotransmitter synthesis. Autosomal recessive or dominant inheritance from ~300 predominantly missense ALPL (also known as TNSALP) mutations largely accounts for the remarkably broad-ranging expressivity of hypophosphatasia. High serum concentrations of pyridoxal 5'-phosphate represent a sensitive and specific biochemical marker for hypophosphatasia. Also, phosphoethanolamine levels are usually elevated in serum and urine, though less reliably for diagnosis. TNSALP mutation detection is important for recurrence risk assessment and prenatal diagnosis. Diagnosing paediatric hypophosphatasia is aided by pathognomic radiographic changes when the skeletal disease is severe. Hypophosphatasia was the last type of rickets or osteomalacia to await a medical treatment. Now, significant successes for severely affected paediatric patients are recognized using asfotase alfa, a bone-targeted recombinant TNSALP. PMID- 26893266 TI - Obesity: PKR not involved in metabolic diseases. PMID- 26893268 TI - Simultaneous quantitative analysis of nine vitamin D compounds in human blood using LC-MS/MS. AB - AIM: It has been suggested that each member of the family of vitamin D compounds may have different function(s). Therefore, selective quantification of each compound is important in clinical research. MATERIALS & METHODS: Development and validation attempts of a simultaneous determination method of 12 vitamin D compounds in human blood using precolumn derivatization followed by LC-MS/MS is described. Internal standard calibration with 12 stable isotope labeled analogs was used to correct for matrix effects in MS detector. RESULTS & CONCLUSION: Nine vitamin D compounds were quantifiable in blood samples with detection limits within femtomole levels. Serum (compared with plasma) was found to be a more suitable sample type, and protein precipitation (compared with saponification) a more effective extraction method for vitamin D assay. PMID- 26893269 TI - Photocurrent in Multilayered Assemblies of Porphyrin-Fullerene Covalent Dyads: Evidence for Channels for Charge Transport. AB - Specially designed porphyrin-fullerene dyads have been synthesized to verify literature predictions based on quantum chemistry calculations that certain porphyrin-fullerene dyads are able to self-arrange into specific structures providing channels for charge transport in a bulk mass of organic compound. According to AFM and SEM data, the newly synthesized compounds were indeed prone to some kind of self-arrangement, although to a lesser degree than was expected. A dispersion corrected DFT study of the molecular non-covalent interactions performed at the DFT-D3 (B3LYP, 6-31G*) level of theory showed that the least energy corresponded to head-to-head dimers, with close contacts of porphyrin porphyrin and fullerene-fullerene fragments, thus providing a unit building block of the channel for charge transport. Experimental proof for the existence of channels for charge transport was obtained by observing a photocurrent in a simple photovoltaic cell. PMID- 26893262 TI - Diabetic emergencies - ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. AB - Diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and hypoglycaemia are serious complications of diabetes mellitus that require prompt recognition, diagnosis and treatment. DKA and HHS are characterized by insulinopaenia and severe hyperglycaemia; clinically, these two conditions differ only by the degree of dehydration and the severity of metabolic acidosis. The overall mortality recorded among children and adults with DKA is <1%. Mortality among patients with HHS is ~10-fold higher than that associated with DKA. The prognosis and outcome of patients with DKA or HHS are determined by the severity of dehydration, the presence of comorbidities and age >60 years. The estimated annual cost of hospital treatment for patients experiencing hyperglycaemic crises in the USA exceeds US$2 billion. Hypoglycaemia is a frequent and serious adverse effect of antidiabetic therapy that is associated with both immediate and delayed adverse clinical outcomes, as well as increased economic costs. Inpatients who develop hypoglycaemia are likely to experience a long duration of hospital stay and increased mortality. This Review describes the clinical presentation, precipitating causes, diagnosis and acute management of these diabetic emergencies, including a discussion of practical strategies for their prevention. PMID- 26893270 TI - Efficacy and safety of minoxidil 3% lotion for beard enhancement: A randomized, double-masked, placebo-controlled study. PMID- 26893271 TI - Frozen section analysis of unusual small testicular tumor masses: report of 3 cases. AB - PURPOSE: Nonpalpable tumors of the testis are generally incidental findings on ultrasound examination. Most of these tumors are benign but some turn out to be germinal tumors at histology. Therefore, intraoperative histopathologic analysis of nonpalpable testicular lesions is pivotal for guiding a testis-sparing surgical approach. METHODS: We report clinical and pathologic characteristics of 3 small nodules of the testis with challenging histologic features at intraoperative frozen section examination and peculiar histology. One was a known testicular mass, undertreated for 5 years, whose enlargement worried the patient, while the other 2 were incidental findings during clinical testicular examination for non-neoplastic diseases. CONCLUSIONS: The 3 cases reported are characterized by small size, which limited the accuracy of preoperative ultrasound diagnosis. Intraoperative frozen section examination was able to rule out a diagnosis of germ cell malignancy in all cases, but diagnosis was conclusive only at histology. Knowledge of unexpected rare testicular lesions is of great relevance at the time of frozen section examination in view of conservative surgical strategy. PMID- 26893274 TI - Sensate Vagina Pedicled-Spot for Male-to-Female Transsexuals: The Experience in the First 50 Patients. AB - BACKGROUND: The cosmetic and functional results of vaginoplasty by inversion of penile and scrotal skin in male-to-female transsexuals are, in general, satisfactory. The sexual arousal function of the neo-female genitalia depends mainly on the clitoris. Due to the lack of a sexual arousal organ within the neo vagina, patients are denied sexual arousal during penetration of the neo-vagina. This necessitated improvement of sexual innervation within the neo-vagina. METHODS: A new technique to create a sexual arousal organ in the anterior wall of the neo-vagina by creation of a sensate pedicled-spot, in combination with the neo-clitoroplasty. RESULTS: In this paper, this new technique and part of the long-term results in the first 50 patients with a sensate pedicled-spot plasty are presented and discussed. CONCLUSIONS: Sensate pedicled-spot plasty has proven to be a safe innovative technique which lead to adequate sexual functionality in all patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893264 TI - BMP signalling in skeletal development, disease and repair. AB - Since the identification in 1988 of bone morphogenetic protein 2 (BMP2) as a potent inducer of bone and cartilage formation, BMP superfamily signalling has become one of the most heavily investigated topics in vertebrate skeletal biology. Whereas a large part of this research has focused on the roles of BMP2, BMP4 and BMP7 in the formation and repair of endochondral bone, a large number of BMP superfamily molecules have now been implicated in almost all aspects of bone, cartilage and joint biology. As modulating BMP signalling is currently a major therapeutic target, our rapidly expanding knowledge of how BMP superfamily signalling affects most tissue types of the skeletal system creates enormous potential to translate basic research findings into successful clinical therapies that improve bone mass or quality, ameliorate diseases of skeletal overgrowth, and repair damage to bone and joints. This Review examines the genetic evidence implicating BMP superfamily signalling in vertebrate bone and joint development, discusses a selection of human skeletal disorders associated with altered BMP signalling and summarizes the status of modulating the BMP pathway as a therapeutic target for skeletal trauma and disease. PMID- 26893273 TI - Autologous Breast Augmentation Using Abdominal Dermis Fat Strip Grafts: A Preliminary Report. AB - BACKGROUND: Abdominoplasty and augmentation mastopexy are often performed in the same operation. Although silicone breast implants are usually used for breast augmentation, resected abdominal dermis fat tissue can be used for this purpose. We describe a new autologous breast augmentation technique using dermis fat grafts obtained from a simultaneous abdominoplasty operation. METHODS: This new technique was used in eight breasts of four patients who requested abdominoplasty and augmentation mastopexy operations in the same session. First, excess abdominal skin was de-epithelized. Dermis fat strips were harvested either in situ or extracorporeally from this area. The prepared strips were then inserted into the pectoralis major muscle during the mastopexy operation. RESULTS: The patients were followed up for 7 months to 6 years. No infection or other problems regarding the technique were observed. Magnetic resonance imaging obtained from one patient showed graft survival after 2 years. A slight augmentation, presumably 50 to 100 mL, was observed per breast in all of the patients. CONCLUSION: Dermis fat strips obtained from an abdominoplasty operation can be used to obtain slight augmentation during mastopexy in patients requesting both of these operations in the same session. Validation of this new technique requires more experience with additional patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893272 TI - Clinical and pathologic predictors of clinical outcome of malignant pleural mesothelioma. AB - AIMS AND BACKGROUND: Although worldwide use of asbestos has decreased, the incidence of malignant pleural mesothelioma (MPM) is expected to increase over the next few decades. A number of scoring systems has been proposed to assess clinicopathologic features and to predict the prognosis. We assessed the relationship between patients' features and disease evolution in order to choose the best treatment able to prolong overall survival (OS) and progression-free survival (PFS). METHODS: We retrospectively analyzed patients with locally advanced or metastatic MPM, treated at the Department of Medical Oncology, Universita Politecnica Marche, Italy, from January 2003 to September 2013. Data on age, sex, smoking history, asbestos exposure, performance status, tumor stage, histology, type of treatment, and routine laboratory tests including complete blood count panel, date of death, or censored status were collected. The OS and PFS were estimated using Kaplan-Meier method and Cox analysis was performed to analyze the prognostic relevance of clinical parameters. RESULTS: We enrolled a total of 62 patients. Univariate analysis showed that histologic type, performance status, response to first-line therapy, pretreatment hemoglobin levels, and plasmatic Ca125 were significant prognostic factors. Conversely, no significant correlation was found between age, sex, smoking history, reported exposure to asbestos, stages at diagnosis, treatments, and OS and PFS. CONCLUSIONS: Our results showed that anemia and increased Ca125 might be considered negative prognostic parameters in MPM patients and confirmed the prognostic role of histotype, performance status, and response to first-line chemotherapy. PMID- 26893275 TI - Siliconoma: Report of Two Cases. AB - Injectable silicone has been used illegally for more than 60 years. Siliconoma is the term used to describe a foreign body reaction in the human body caused by the presence of silicone. The aim of this study is to report two cases of patients who underwent application of large volumes of injectable silicone with non medical and unqualified professionals, which led to serious complications sometime after the procedure. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893277 TI - Perfect Lighting for Facial Photography in Aesthetic Surgery: Ring Light. AB - INTRODUCTION: Photography is indispensable for plastic surgery. On-camera flashes can result in bleached out detail and colour. This is why most of the plastic surgery clinics prefer studio lighting similar to professional photographers'. In this article, we want to share a simple alternative to studio lighting that does not need extra space: Ring light. METHODS: We took five different photographs of the same person with five different camera and lighting settings: Smartphone and ring light; point and shoot camera and on-camera flash; point and shoot camera and studio lighting; digital single-lens reflex (DLSR) camera and studio lighting; DSLR and ring light. Then, those photographs were assessed objectively with an online survey of five questions answered by three distinct populations: plastic surgeons (n: 28), professional portrait photographers (n: 24) and patients (n: 22) who had facial aesthetic procedures. RESULTS: Compared to the on camera flash, studio lighting better showed the wrinkles of the subject. The ring light facilitated the perception of the wrinkles by providing homogenous soft light in a circular shape rather than bursting flashes. The combination of a DSLR camera and ring light gave the oldest looking subject according to 64 % of responders. The DSLR camera and the studio lighting demonstrated the youngest looking subject according to 70 % of the responders. The majority of the responders (78 %) chose the combination of DSLR camera and ring light that exhibited the wrinkles the most. CONCLUSIONS: We suggest using a ring light to obtain well-lit photographs without loss of detail, with any type of cameras. However, smartphones must be avoided if standard pictures are desired. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893276 TI - Consensus on Current Injectable Treatment Strategies in the Asian Face. AB - BACKGROUND: The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. METHOD: The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. RESULTS: The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to >55 years are presented. CONCLUSIONS: In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893278 TI - Safe Planes for Injection Rhinoplasty: A Histological Analysis of Midline Longitudinal Sections of the Asian Nose. AB - BACKGROUND: Dorsal nasal augmentation is an essential part of injection rhinoplasty on the Asian nose. Aesthetic physicians require detailed knowledge of the nasal anatomy to accurately and safely inject filler. METHODS: One hundred and thirty-five histological cross sections were examined from 45 longitudinal strips of soft tissue harvested from the midline of the nose, beginning from the glabella to the nasal tip. Muscles and nasal cartilage were used as landmarks for vascular identification. RESULTS: At the nasal tip, a midline longitudinal columellar artery with a diameter of 0.21 +/- 0.09 mm was noted in 14 cadavers (31.1 %). At the infratip, subcutaneous tissue contained cavernous tissue similar to that of the nasal mucosa. The feeding arteries of these dilated veins formed arteriovenous shunts, into which retrograde injection of filler may be possible. All of the nasal arteries present were identified as subcutaneous arteries. They coursed mainly in the superficial layer of the subcutaneous tissues, with smaller branches forming subdermal plexuses. A substantial arterial anastomosis occurred at the supratip region, in which the artery lay in the middle of the subcutaneous tissue at the level of the major alar cartilages. These arteries had a diameter ranging between 0.4 and 0.9 mm and were found in 29 of 45 specimens (64.4 %). This was at the level midway between the rhinion above the supratip and the infratip. This anastomotic artery also crossed the midline at the rhinion superficial to the origin of the procerus on the lower end of the nasal bone. Here the arterial diameter ranged between 0.1 and 0.3 mm, which was not large enough to cause arterial emboli. Fascicular cross sections of the nasalis muscle directly covered the entire upper lateral cartilage. The subdermal tissue contained few layers of fat cells along with the occasional small artery. The procerus arose from the nasal bone and was continuous with the nasalis in 16 cadavers (35.6 %). There was fatty areolar tissue between the procerus and the periosteal layer and no significant arteries present. The procerus ascended beyond the brow to insert into the frontalis muscle with very few cutaneous insertions. The supratrochlear vessels and accompanying nerve were occasionally found on the surface of the frontalis muscle. CONCLUSION: Most nasal arteries found in the midline are subcutaneous arteries. Filler should be injected deeply to avoid vascular injury leading to compromised perfusion at the dorsum or filler emboli at the nasal tip. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893279 TI - Use of Platelet Preparations in Facial Rejuvenation and Wound Healing Remains Unproven. AB - There is growing interest in the use of platelet derivatives in facial aesthetic surgery and wound healing. Sclafani et al. have concluded from their review of the literature that the vast majority of studies show a significant and measurable effect on facial aesthetic outcomes with the use of these platelet preparations. We suggest that an alternative review of the same literature may well have produced a different set of conclusions. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893281 TI - Upper Eyelid Filling With or Without Surgical Treatment. AB - BACKGROUND: The upper eyelid of young people is characterized by a proper fullness and projection. Aging eyes show upper eyelid volume loss, symmetric or asymmetric hollowing with too much upper lid showing, dermatochalasis with skin excess. While in the past blepharoplasty surgery was the only approach used to improve eye appearance in the last years, hyaluronic acid (HA) filling of the upper eyelid area has been found very effective in reaching good eye rejuvenation and use of traditional surgical techniques can be limited. METHODS: A total of 154 patients were enrolled in this study to improve eye appearance. One hundred twenty-eight patients were treated with HA injections in the upper eyelid only, 21 patients underwent surgical treatment followed by HA injections to ensure full correction, and 5 patients underwent blepharoplasty surgery only. The correct approach has been evaluated on the basis of standardized criterion. RESULTS: Twelve-month clinical follow-up was used to evaluate the results and the degree of patient satisfaction was high. The results are very lasting and no modifications after 2 years are common. CONCLUSIONS: HA filling is an effective means to rejuvenate the upper eyelid and in several cases it is the only approach able to restore the proper fullness of the upper eyelids. Surgical techniques should be used in the presence of dermatochalasis with excess skin. HA injections in the upper eyelid are easy to perform but it is important to use the correct technique and follow proper indications. This method is a manageable, lasting, and low-cost treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893280 TI - Cell-Assisted Lipotransfer: A Systematic Review of Its Efficacy. AB - INTRODUCTION: Autologous lipotransfer is seen as an ideal filler for soft tissue reconstruction. The main limitation of this procedure is the unpredictable resorption and volume loss of the fat graft. In the recent decade, an increasing amount of research has focused on the use of adipose tissue-derived stromal cells (ASCs) to enrich the fat graft, a procedure termed cell-assisted lipotransfer (CAL). The aim of this review was to systematically review the current preclinical and clinical evidence for the efficacy of CAL compared with conventional lipotransfer. MATERIALS AND METHODS: A systematic search was performed on PubMed and other databases to identify all preclinical and clinical studies where CAL with ASCs was compared with conventional lipotransfer. A total of 20 preclinical studies and seven clinical studies were included in the review. RESULTS: The preclinical studies consisted of 15 studies using immunodeficient animal models and five studies using immunocompetent studies. Seventeen studies examined weight/volume retention of which 15 studies favored CAL over conventional lipotransfer. One clinical study did not find any efficacy of CAL and the remaining six studies favored CAL. CONCLUSIONS: The present evidence suggests that there is a big potential for CAL in reconstructive surgery; however, the present studies are so far still of low quality with inherent weaknesses. Several aspects regarding CAL still remain unknown such as the optimal degree of cell enrichment and also its safety. Further high-quality studies are needed to establish if CAL can live up to its potential. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893282 TI - Enhancing Masculine Features After Massive Weight Loss. AB - BACKGROUND: Whereas body contouring surgery after massive weight loss in women emphasizes sculptured adipose and broader lower torso, little attention has been devoted to accentuating the male physique. OBJECTIVE: To determine if boomerang excision pattern correction of gynecomastia with J torsoplasty combined with an abdominoplasty with oblique excisions directly over bulging flanks provide effective and safe optimizing of muscle visibility and upper torso dominance. METHODS: A description of comprehensive body contouring through an abdominoplasty and a series of obliquely oriented ellipses of the male torso is followed by review of 19 consecutive patients. RESULTS: Seventeen patients were performed in a single stage. Nine of the last ten cases included J torsoplasty and oblique excision extensions over the flanks. Of the 17 patients responding to a ten question survey, 15 were satisfied with chest improvement. One of the first eight patients with a transverse lower body lift was satisfied with the flank bulges. All of the last eight cases with direct oblique flank excisions were satisfied with their lower body. Five patients (26 %), having a total of 74 operative procedures, had significant complications of chest hematoma, persistent hip and buttock seromas, superior NAC edge necrosis, and distal necrosis of the fleur de lis abdominoplasty. One boomerang correction underwent minor revisions. One transverse lower body lift underwent major revision. No complications occurred in the last ten patients, having oblique flank excisions instead of transverse lower body lifts. CONCLUSION: Comprehensive excisional body contouring surgery of a central high tension abdominoplasty with a series of obliquely oriented ellipses throughout the torso appears to provide low risk improved body contour for the muscular male. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893283 TI - Public's Knowledge and Attitudes Toward Vascularized Composite Allotransplantation and Donation. AB - BACKGROUND: The purpose of this survey was to assess the public's knowledge and attitudes toward vascularized composite allotransplantation and donation. METHODS: Members of the public (n = 5942) were surveyed using a questionnaire that examined their knowledge and attitudes concerning solid organs (kidney, heart, liver, lung, and pancreas) and vascularized composite tissue (hand/upper extremity, lower extremity, abdominal wall, and face) transplantations and donations. RESULTS: Respondents demonstrated greater (all P < 0.05) knowledge and willingness to donate and/or receive solid organs than vascularized composite tissues. Educational level, accurate knowledge, willingness to donate, and willingness to receive were significant (all P < 0.05) determinants of acceptance to donate and/or receive hand/upper extremity, lower extremity, face, and/or abdominal wall. CONCLUSION: The public presented less knowledge and willingness to donate and/or receive hand/upper extremity, lower extremity, abdominal wall, and face. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26893284 TI - Methamphetamine use is associated with high levels of depressive symptoms in adolescents and young adults in Rural Chiang Mai Province, Thailand. AB - BACKGROUND: High levels of depressive symptoms often occur among individuals that use or that are dependent on methamphetamine (MA). Thailand is currently experiencing an epidemic of MA use among youth. Understanding the nature of the relationship between depressive symptoms and MA use and identifying those most at risk can further understanding of prevention and treatment options for youth who use MA and present with depressive symptoms. METHODS: In 2011, we conducted a cross sectional epidemiologic study that examined associations between MA use and high levels of depressive symptoms among adolescents and young adults aged 14-29 living in Chiang Mai province, Thailand. A combination of cluster and systematic sampling was conducted to obtain a study sample of participants actively recruited in Chiang Mai province. Depressive symptoms were measured using a Thai translation of the Centers for Epidemiologic Studies Depression scale (CES-D). The independent variables measured reported lifetime and recent MA use within the past 3 months. Multivariate logistic regression models were used to assess associations between MA use and high levels of depressive symptoms. RESULTS: Approximately 19% (n = 394) of the sample reported ever having consumed MA and 31% (n = 124) of lifetime users reported recent MA use within the past 3 months. Recent MA use was associated with high levels of depressive symptoms (aPOR recent use: 2.60, 95% CI: 1.20, 5.63). CONCLUSIONS: This is one of the first studies to examine the association between MA use and high levels of depressive symptoms in a general Thai population. The odds of having high levels of depressive symptoms was significantly greater among recent MA users compared to non-users. These findings support the need for policies, programs and interventions to prevent and treat depressive symptoms presenting among MA using Thai adolescents and young adults in rural Chiang Mai province, Thailand to aid in cessation of MA use. Furthermore, additional research is needed to investigate treatment options for adolescents and young adults in Thailand that use MA and present with high levels of depressive symptoms. PMID- 26893287 TI - Allylic amination reactivity of Ni, Pd, and Pt heterobimetallic and monometallic complexes. AB - Transition metal heterobimetallic complexes with dative metal-metal interactions have the potential for novel fast reactivity. There are few studies that both compare the reactivity of different metal centers in heterobimetallic complexes and compare bimetallic reactivity to monometallic reactivity. Here we report density-functional calculations that show the reactivity of [Cl2Ti(N(t)BuPPh2)2M(II)(eta(3)-methallyl)] heterobimetallic complexes for allylic amination follows M = Ni > Pd > Pt. This reactivity trend was not anticipated since the amine addition transition state involves M(II) to M(0) reduction and this could disadvantage Ni. Comparison of heterobimetallic complexes to the corresponding monometallic (CH2)2(N(t)BuPPh2)2M(II)(eta(3) methallyl) complexes reveals that this reactivity trend is due to the bimetallic interaction and that the bimetallic interaction significantly lowers the barrier height for amine addition by >10 kcal mol(-1). The impact of the early transition metal center on the amination addition barrier height depends on the late transition metal center. The lowest barrier heights for this reaction occur when late and early transition metal centers are from the same periodic table row. PMID- 26893285 TI - Psychological intervention targeting distress for cancer patients: a meta analytic study investigating uptake and adherence. AB - OBJECTIVE: Although cancer care guidelines recommend screening for distress among cancer patients and offering psychological support when indicated, many patients decline offers of such support. This study aimed to quantify uptake and adherence to psychological support and to identify predictors of each. METHODS: Searches were conducted in Embase, Medline, PsychInfo and Scopus to identify studies reporting uptake or adherence rates for individual psychological interventions targeting distress, anxiety or depression for cancer patients or survivors. RESULTS: Across the 53 included studies reporting uptake and/or adherence rates for 12 323 cancer patients, the uptake and adherence rates were 60.1% and 90.4%, respectively. Patients screened and identified as distressed were less likely to accept intervention than unselected patients (50.3% compared with 66.3%, Q(1) = 4.66, P = 0.031). Uptake of therapy was higher for interventions delivered by telephone rather than face-to-face (71.2% compared with 53.8%, Q(1) = 4.91, P = 0.027) and when therapy was offered prior to medical treatment compared with later (72.9% compared with 56.8%, Q(1) = 5.60, P = 0.018). Patients were more likely to accept intervention from nurses than other allied health professionals (68.3% compared with 50.5%, Q(1) = 5.76, P = 0.016). CONCLUSIONS: Patients appeared more receptive to interventions offered near diagnosis, over the telephone and by nurses. Although this suggests higher acceptability of such interventions, evidence of their greater efficacy is lacking, and this merits further investigation. Research is needed to understand barriers to acceptance of psychological support, particularly because uptake rates were lower for distressed patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26893289 TI - Synthesis of rocaglamide derivatives and evaluation of their Wnt signal inhibitory activities. AB - Rocaglamides are bioactive natural compounds which have a cyclopenta[b]benzofuran core structure. The total synthesis of a reported natural product, 3' hydroxymethylrocaglate (5), was achieved using [3 + 2] cycloaddition between 3 hydroxyflavone and methyl cinnamate. We also describe the synthesis of rocaglamide heterocycle derivatives and evaluate their Wnt signal inhibitory activities. Compounds 4, 5, 22a, 22b, 22c and 23c showed potent Wnt signal inhibitory activity. PMID- 26893288 TI - Cep70 overexpression stimulates pancreatic cancer by inducing centrosome abnormality and microtubule disorganization. AB - The centrosome is crucial for mitotic fidelity, and centrosome aberrations are associated with genomic instability and tumorigenesis. The centrosomal protein Cep70 has been reported to play a role in various cellular activities. However, whether this protein is involved in pathological processes remains unknown. In this study, we demonstrate that Cep70 is highly expressed in pancreatic cancer tissues. Cep70 expression correlates with clinicopathological parameters of pancreatic cancer, including histological grade, pathological tumor node metastasis stage, lymph node metastasis, and carbohydrate antigen 19-9 level. Depletion of Cep70 significantly suppresses pancreatic cancer cell proliferation and promotes apoptotic cell death, and exogenous expression of Cep70 can rescue the above effects. Cep70 also stimulates colony formation in soft agar and enhances tumor growth in mice. Our data further show that ectopic expression of Cep70 in pancreatic cancer cells results in the mislocalization of centrosomal proteins, including gamma-tubulin and pericentrin, and the formation of intracellular aggregates. In addition, Cep70 overexpression leads to microtubule disorganization and the formation of multipolar spindles during mitosis. Our study thus unravels a critical role for Cep70 in pancreatic cancer and suggests Cep70 as a potential biomarker and therapeutic target for this deadly disease. PMID- 26893290 TI - Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells. AB - PURPOSE: Clinical evidence of retinal pigment epithelium (RPE) alterations after intra-arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model. METHODS: The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7-activity assays after a 24-hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively. RESULTS: We observed a concentration-dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements. CONCLUSIONS: Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients. PMID- 26893291 TI - Toxicity study of ochratoxin A using HEK293 and HepG2 cell lines based on microRNA profiling. AB - Ochratoxin A (OTA) induced DNA damage, cytotoxicity, and apoptosis in mammalian cell lines. Micro RNAs (miRNAs) are involved in physiological and developmental processes and contribute to cancer development and progression. In our study, high-throughput miRNA profiling and Kyoto Encyclopedia of Genes and Genomes analysis were applied to comparatively study the toxicity of OTA in HEK293 cells and HepG2 cells treated with 25 MUM OTA for 24 h. In these two cells, the same changing miRNAs were mostly related to signal transduction pathways, whereas the different changing miRNAs were mostly related to human cancer pathways. DGCR8, Dicer1, and Drosha were significantly suppressed in HEK293 cells, indicating an impairment of miRNA biogenesis. The damage seemed more extensive in HEK293 cells. Cell models and in vivo models were also compared. Many miRNAs in vitro were markedly different from those in vivo; however, OTA toxicity was observed both in vitro and in vivo. The classification of deregulated pathways is similar. The biogenesis of miRNA was impaired in both lines. In conclusion, deregulated miRNAs in vitro are mostly related to human cancer and signal transduction pathways. The deregulated pathways in vivo are similar to those in vitro. PMID- 26893292 TI - Taming the White Bear: Initial Costs and Eventual Benefits of Distractor Inhibition. AB - Previous research indicates that prior information about a target feature, such as its color, can speed search. Can search also be speeded by knowing what a target willnotlook like? In the two experiments reported here, participants searched for target letters. Prior to viewing search displays, participants were prompted either with the color in which one or more nontarget letters would appear (ignore trials) or with no information about the search display (neutral trials). Critically, when participants were given one consistent color to ignore for the duration of the experiment, compared with when they were given no information, there was a cost in reaction time (RT) early in the experiment. However, after extended practice, RTs on ignore trials were significantly faster than RTs on neutral trials, which provides a novel demonstration that knowledge about nontargets can improve search performance for targets. When the to-be ignored color changed from trial to trial, no RT benefit was observed. PMID- 26893293 TI - Economic Insecurity Increases Physical Pain. AB - The past decade has seen a rise in both economic insecurity and frequency of physical pain. The current research reveals a causal connection between these two growing and consequential social trends. In five studies, we found that economic insecurity produced physical pain and reduced pain tolerance. In a sixth study, with data from 33,720 geographically diverse households across the United States, economic insecurity predicted consumption of over-the-counter painkillers. The link between economic insecurity and physical pain emerged when people experienced the insecurity personally (unemployment), when they were in an insecure context (they were informed that their state had a relatively high level of unemployment), and when they contemplated past and future economic insecurity. Using both experimental-causal-chain and measurement-of-mediation approaches, we also established that the psychological experience of lacking control helped generate the causal link from economic insecurity to physical pain. Meta-analyses including all of our studies testing the link from economic insecurity to physical pain revealed that this link is reliable. Overall, the findings show that it physically hurts to be economically insecure. PMID- 26893294 TI - Improving self-referral for diabetes care following hypoglycaemic emergencies: a feasibility study with linked patient data analysis. AB - BACKGROUND: Hypoglycaemia is a common and potentially life threatening consequence of insulin and sulphonylurea treated Diabetes. Some severe hypoglycaemic events result in emergency ambulance attendance. Many of these patients are treated at home and do not require immediate transportation to an Emergency Department. However only 27-37 % of patients then follow up their care with a diabetes specialist. Consequently repeat severe hypoglycaemic events occur. METHODS: The intervention was implemented for 8 months, using a prospective cohort design with a historic control, in one Scottish Health Board in 2012. Data was collected using postal survey questionnaires to patients and ambulance clinicians, telephone survey follow-up questions to patients. Scottish Ambulance Service electronic records were linked with the SCI-Diabetes database of patient records to enable objective measurement of follow-up behaviour. RESULTS: Ambulance clinicians' (n = 92) awareness of the intervention was high and both the prompt card and telephone call components of the intervention were delivered to most eligible patients. The intervention was perceived as highly acceptable to patients (n = 37), and very useful by both patients and ambulance clinicians. However, comparison of patient follow-up behaviours using linked-data (n = 205), suggest that the intervention was unsuccessful in improving rates of patients' following up their care. CONCLUSIONS: This study shows that the intervention is implementable, highly acceptable to patients, and considered very useful by both patients and ambulance clinicians. However, preliminary evidence of effectiveness is not encouraging. The study's novel use of linking existing clinical data for outcome measurement exposed challenges in the feasibility of using this data for intervention development and evaluation. Future research should examine challenges to the successful testing and effectiveness of the intervention. Revisions are likely to be required, both to study design and the optimisation of the intervention's content and components. PMID- 26893296 TI - Disability and HIV in Africa: Breaking the barriers to sexual health care. AB - Three decades into the HIV pandemic, the issues affecting people with disabilities remain less known. Increasing attention has been given to this overlooked population when it comes to HIV prevention, treatment and care. This is related to the significant unmet sexual and reproductive healthcare needs facing people with disabilities worldwide. This article discusses the barriers to sexual health for people with disabilities in Africa and presents an argument about how mainstream HIV prevention work and research do not adequately attend to the sorts of systemic barriers that exclude people with disabilities, which a more targeted and critical approach could. PMID- 26893295 TI - Cultural adaptation of a cognitive-behavioural intervention to improve adherence to antiretroviral therapy among people living with HIV/AIDS in Zimbabwe: Nzira Itsva. AB - Few evidence-based interventions to improve adherence to antiretroviral therapy have been adapted for use in Africa. We selected, culturally adapted and tested the feasibility of a cognitive-behavioural intervention for adherence and for delivery in a clinic setting in Harare, Zimbabwe. The feasibility of the intervention was evaluated using a mixed-methods assessment, including ratings of provider fidelity of intervention delivery, and qualitative assessments of feasibility using individual semi-structured interviews with counsellors (n=4) and patients (n=15). The intervention was feasible and acceptable when administered to 42 patients and resulted in improved self-reported adherence in a subset of 15 patients who were followed up after 6months. PMID- 26893298 TI - Editorial: Remarks From the Dean on the Centennial of the Johns Hopkins Bloomberg School of Public Health. PMID- 26893299 TI - Leadership of the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health in Its First Century. AB - This commentary reviews the contributions of each of the 7 Chairs of the Department of Epidemiology from the Department's inception in 1919 to the advent of the Centennial Celebration of the Johns Hopkins Bloomberg School of Public Health in 2016. The founding Chair, Wade Hampton Frost (1919-1938), was among the handful of foundational thinkers in the discipline of epidemiology. Kenneth Maxcy (1938-1954) and Philip Sartwell (1954-1970) oversaw the Department through the epidemiologic transition from a preponderance of morbidity and mortality due to infectious diseases to a preponderance of noncommunicable diseases. Abraham Lilienfeld (1970-1975) and Leon Gordis (1975-1993) were perhaps best known for their mastery of teaching, influencing generations of both medical and public health students. Jonathan Samet (1994-2008) oversaw a major curriculum revision and expanded the Department significantly, and David Celentano (2008-) is working to rebalance the practice of epidemiology with the etiological foundations of epidemiology. All Chairs were a product of their times, and their research focus and portfolios influenced the direction of the Department. Future generations of Johns Hopkins students will be influenced directly or indirectly by the heritage of these Chairs' actions and those of their faculty. PMID- 26893297 TI - Mechanistic Models of Infectious Disease and Their Impact on Public Health. AB - From the 1930s through the 1940s, Lowell Reed and Wade Hampton Frost used mathematical models and mechanical epidemic simulators as research tools and to teach epidemic theory to students at the Johns Hopkins Bloomberg School of Public Health (then the School of Hygiene and Public Health). Since that time, modeling has become an integral part of epidemiology and public health. Models have been used for explanatory and inferential purposes, as well as in planning and implementing public health responses. In this article, we review a selection of developments in the history of modeling of infectious disease dynamics over the past 100 years. We also identify trends in model development and use and speculate as to the future use of models in infectious disease dynamics. PMID- 26893300 TI - Tracing the Archaeal Origins of Eukaryotic Membrane-Trafficking System Building Blocks. AB - In contrast to prokaryotes, eukaryotic cells are characterized by a complex set of internal membrane-bound compartments. A subset of these, and the protein machineries that move material between them, define the membrane-trafficking system (MTS), the emergence of which represents a landmark in eukaryotic evolution. Unlike mitochondria and plastids, MTS organelles have autogenous origins. Much of the MTS machinery is composed of building blocks, including small GTPase, coiled-coil, beta-propeller + alpha-solenoid, and longin domains. Despite the identification of prokaryotic proteins containing these domains, only few represent direct orthologues, leaving the origins and early evolution of the MTS poorly understood. Here, we present an in-depth analysis of MTS building block homologues in the composite genome of Lokiarchaeum, the recently discovered archaeal sister clade of eukaryotes, yielding several key insights. We identify two previously unreported Eukaryotic Signature Proteins; orthologues of the Gtr/Rag family GTPases, involved in target of rapamycin complex signaling, and of the RLC7 dynein component. We could not identify golgin or SNARE (coiled-coil) or beta-propeller + alpha-solenoid orthologues, nor typical MTS domain fusions, suggesting that these either were lost from Lokiarchaeum or emerged later in eukaryotic evolution. Furthermore, our phylogenetic analyses of lokiarchaeal GTPases support a split into Ras-like and Arf-like superfamilies, with different prokaryotic antecedents, before the advent of eukaryotes. While no GTPase activating proteins or exchange factors were identified, we show that Lokiarchaeum encodes numerous roadblock domain proteins and putative longin domain proteins, confirming the latter's origin from Archaea. Altogether, our study provides new insights into the emergence and early evolution of the eukaryotic membrane-trafficking system. PMID- 26893301 TI - Clustering Genes of Common Evolutionary History. AB - Phylogenetic inference can potentially result in a more accurate tree using data from multiple loci. However, if the loci are incongruent-due to events such as incomplete lineage sorting or horizontal gene transfer-it can be misleading to infer a single tree. To address this, many previous contributions have taken a mechanistic approach, by modeling specific processes. Alternatively, one can cluster loci without assuming how these incongruencies might arise. Such "process agnostic" approaches typically infer a tree for each locus and cluster these. There are, however, many possible combinations of tree distance and clustering methods; their comparative performance in the context of tree incongruence is largely unknown. Furthermore, because standard model selection criteria such as AIC cannot be applied to problems with a variable number of topologies, the issue of inferring the optimal number of clusters is poorly understood. Here, we perform a large-scale simulation study of phylogenetic distances and clustering methods to infer loci of common evolutionary history. We observe that the best performing combinations are distances accounting for branch lengths followed by spectral clustering or Ward's method. We also introduce two statistical tests to infer the optimal number of clusters and show that they strongly outperform the silhouette criterion, a general-purpose heuristic. We illustrate the usefulness of the approach by 1) identifying errors in a previous phylogenetic analysis of yeast species and 2) identifying topological incongruence among newly sequenced loci of the globeflower fly genus Chiastocheta We release treeCl, a new program to cluster genes of common evolutionary history (http://git.io/treeCl). PMID- 26893302 TI - Fatal arterial rupture during angioplasty of a flow diverter in a recurrent, previously Y-stented giant MCA bifurcation aneurysm. AB - BACKGROUND AND PURPOSE: A patient with a previously Y-stented giant left middle cerebral artery (MCA) bifurcation aneurysm returned with a recurrence. MATERIALS AND METHODS: A flow diverter (FD) was deployed through one limb of the high porosity Y-stenting construction. The proximal FD failed to expand and an attempt at balloon angioplasty led to fatal rupture of the MCA. RESULTS: Autopsy demonstrated subarachnoid hemorrhage, vessel rupture and fracture of the proximal high-porosity stent. Microscopic photographs showed that the FD had failed to open because the guiding wire had inadvertently exited and re-entered the proximal segment of the high-porosity stent partially incorporated to the wall of the MCA. Balloon dilatation of the FD which had remained collapsed between the stent and the vessel wall caused fracture of the stent and rupture of the artery. CONCLUSION: Angioplasty and flow-diversion of previously Y-stented aneurysms can lead to serious complications. PMID- 26893304 TI - Developing a Personal and Social Identity With Type 1 Diabetes During Adolescence: A Hypothesis Generative Study. AB - This study explored the incorporation of type 1 diabetes mellitus (T1DM) into self-identity among adolescents. Guided interviews explored 40 adolescents' views of T1DM in relation to their sense of self and relationships with others. Responses were analyzed using thematic analysis. Results revealed that the entire sample described T1DM as a significant burden; many described how T1DM made them feel less "normal." Adolescents described both positive and negative aspects of self-management in social relationships, though most reported benefits in sharing T1DM with friends. Females were more likely to share information about T1DM and to describe positive changes in self-perception as a result of T1DM. The psychosocial processes related to integration of T1DM into self-identity described in these qualitative data provide hypothesis-generating findings that can guide future quantitative research examining incorporation of T1DM into adolescent self-identity in relation to measures of self-esteem, peer orientation, self-management, and glycemic control. PMID- 26893303 TI - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model. AB - Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp(-/-)) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murineBcrppromoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP. PMID- 26893305 TI - "I Do Not Really Belong Out There Anymore": Sense of Being and Belonging Among People With Medically Unexplained Long-Term Fatigue. AB - In this article, we explore relations between health, being, belonging and place through an interpretive thematic analysis of autobiographic text and photographs about the everyday lives of 10 women and men living with medically unexplained long-term fatigue in Norway. While interpreting their place-related illness experiences, we ask: How do they experience their being in the world, where do they experience a sense of belonging/not belonging, and why do places become places of belonging/not belonging? The participants describe experiences of (a) being socially detached and alienated, (b) being imprisoned, (c) being spectators who observe the world, and (d) senses of belonging. They describe senses of being and belonging/not belonging as closely attached to physical and symbolic aspects of places in which they reside, and they wistfully reflect on the question of "why." The study illustrates the influence of experienced place-material as well as immaterial-on health and illness. PMID- 26893306 TI - How Not to Let Secrets Out When Conducting Qualitative Research With Dyads. AB - Confidentiality is one of the cornerstones of research involving human participants. Researchers are the frontline gatekeepers of their participants' right to confidentiality, and situations can arise that challenge this responsibility. This is the case when individuals who have shared a common experience (i.e., dyads) are interviewed separately, but interview results are disseminated within the context of dyads. Based on our experience of conducting research with dyads and given how little literature is available to serve as guide, we set out to write this article to share the knowledge we acquired and the solutions we found. We will describe both the ethical challenges and the methodological decisions involved in conducting qualitative research with dyads. The article also describes different modalities of dyadic analysis, their benefits and drawbacks. This endeavor seems especially relevant as research with dyads is emerging in several domains involving couples, families, caregivers and health. PMID- 26893307 TI - ADHD Symptoms in Adolescents' Everyday Life: Fluctuations and Symptom Structure Within and Between Individuals. AB - OBJECTIVE: This study investigated whether self-reported ADHD symptoms fluctuate substantially within adolescents from day to day, and examined the underlying symptom factor structure on a within- and between-person level. METHOD: Adolescents (N = 166) rated their ADHD symptoms over the phone on eight consecutive evenings (total ratings: n = 1,264). RESULTS: ADHD symptoms showed substantial fluctuations within adolescents from day to day, as indicated by within-person standard deviations and intraclass correlation coefficients. Both a two-level factor model with three correlated factors (inattention, hyperactivity, impulsivity) and a two-level bifactor model with a general ADHD symptom factor and a specific inattention factor provided acceptable to good accounts of the structure underlying daily ADHD symptom ratings on the between- and the within person level. CONCLUSION: The study demonstrates that adolescents' ADHD symptoms fluctuate from day to day and highlights the need for intensive diagnostic processes with repeated symptom assessments and interventions that address symptom fluctuations. PMID- 26893308 TI - Positional proteomics reveals differences in N-terminal proteoform stability. AB - To understand the impact of alternative translation initiation on a proteome, we performed a proteome-wide study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. By combining pulsed SILAC with N-terminal COFRADIC, we monitored the stability of 1,941 human N-terminal proteoforms, including 147 N terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. N terminally truncated proteoforms were less abundant than canonical proteoforms and often displayed altered stabilities, likely attributed to individual protein characteristics, including intrinsic disorder, but independent of N-terminal amino acid identity or truncation length. We discovered that the removal of initiator methionine by methionine aminopeptidases reduced the stability of processed proteoforms, while susceptibility for N-terminal acetylation did not seem to influence protein turnover rates. Taken together, our findings reveal differences in protein stability between N-terminal proteoforms and point to a role for alternative translation initiation and co-translational initiator methionine removal, next to alternative splicing, in the overall regulation of proteome homeostasis. PMID- 26893309 TI - Eccentric Exercise Versus Eccentric Exercise and Soft Tissue Treatment (Astym) in the Management of Insertional Achilles Tendinopathy. AB - BACKGROUND: Eccentric exercise is commonly used in the management of Achilles tendinopathy (AT) but its effectiveness for insertional AT has been questioned. Soft tissue treatment (Astym) combined with eccentric exercise could result in better outcomes than eccentric exercise alone. HYPOTHESIS: Soft tissue treatment (Astym) plus eccentric exercise will be more effective than eccentric exercise alone for subjects with insertional AT. STUDY DESIGN: Prospective randomized controlled trial. LEVEL OF EVIDENCE: Level 2. METHODS: Sixteen subjects were randomly assigned to either a soft tissue treatment (Astym) and eccentric exercise group or an eccentric exercise-only group. Intervention was completed over a 12-week period, with outcomes assessed at baseline, 4, 8, 12, 26, and 52 weeks. Outcomes included the Victorian Institute of Sport Assessment Achilles Specific Questionnaire (VISA-A), the numeric pain rating scale (NPRS), and the global rating of change (GROC). RESULTS: Significantly greater improvements on the VISA-A were noted in the soft tissue treatment (Astym) group over the 12-week intervention period, and these differences were maintained at the 26- and 52-week follow-ups. Both groups experienced a similar statistically significant improvement in pain over the short and long term. A significantly greater number of subjects in the soft tissue treatment (Astym) group achieved a successful outcome at 12 weeks. CONCLUSION: Soft tissue treatment (Astym) plus eccentric exercise was more effective than eccentric exercise only at improving function during both short- and long-term follow-up periods. CLINICAL RELEVANCE: Soft tissue treatment (Astym) plus eccentric exercise appears to be a beneficial treatment program that clinicians should consider incorporating into the management of their patients with insertional AT. PMID- 26893310 TI - Early-Onset Mild Type Leukoencephalopathy Caused by a Homozygous EARS2 Mutation. AB - Childhood leukoencephalopathies are a broad class of diseases, which are extremely rare. The treatment and classification of these disorders are both challenging. Nearly half of children presenting with a leukoencephalopathy remain without a specific diagnosis. Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL) is a newly described childhood leukoencephalopathy caused by mutations in the gene encoding a mitochondrial aminoacyl-tRNA synthetase specific for glutamate, EARS2 Magnetic resonance images show a characteristic leukoencephalopathy with thalamic and brain stem involvement. Here, we report a different clinical course of LTBL supported by typical MRI features in a Turkish patient who presented with a history of failure to walk. The EARS2 gene mutation analysis identified a c.322C>T transition, predicting a p.R108W change. This is the first reported early-onset mild type LTBL caused by a homozygous EARS2 mutation case in the literature. PMID- 26893312 TI - Targeting the MEK signaling pathway in non-small cell lung cancer (NSCLC) patients with RAS aberrations. AB - With the advancement in understanding the biology of non-small cell lung cancer (NSCLC), therapies focused on novel molecular pathways have come to the forefront of NSCLC treatment. This review focuses on the preclinical and clinical aspects underlying the targeting of RAS aberrations in NSCLC with special focus on MEK inhibitors which work by inhibiting the principal downstream mediator of RAS aberrations with a view on how to optimize outcomes with these agents. Preclinical evidence of the activity of MEK inhibitors in KRAS-mutant NSCLC has pushed forward the clinical development of these agents (namely selumetinib and trametinib) in KRAS-mutant NSCLC particularly in combination with other agents. A number of randomized studies have been launched to confirm the activity of these agents and to establish their position in the treatment armamentarium of NSCLC. PMID- 26893318 TI - Trends in Extracorporeal Membrane Oxygenation for the Treatment of Acute Respiratory Distress Syndrome in the United States. AB - OBJECTIVES: Our aim was to describe patient characteristics and trends in the use of extracorporeal membrane oxygenation (ECMO) for the treatment of acute respiratory distress syndrome (ARDS) in the United States from 2006 to 2011. METHODS: We used the Nationwide Inpatient Sample to isolate all patients aged 18 years who had a discharge International Classification of Diseases, Ninth Revision diagnosis of ARDS, with and without procedure codes for ECMO, between 2006 and 2011. RESULTS: We examined a total of 47 911 414 hospital discharges, representing 235 911 271 hospitalizations using national weights. Of the 1 479 022 patients meeting the definition of ARDS (representing 7 281 206 discharges), 775 underwent ECMO. There was a 409% relative increase in the use of ECMO for ARDS in the United States between 2006 and 2011, from 0.0178% to 0.090% ( P = .0041). Patients treated with ECMO had higher in-hospital mortality (58.6% vs 25.1%, P < .0001) and longer hospital stays (15.8 days vs 6.9 days, P < .0001). They were also younger (47.9 vs 66.4 years, P < .0001) and more likely to be male (62.2% vs 49.6%, P < .0001). The median time to initiate ECMO from the time of admission was 0.5 days (interquartile range [IQR] 4.9 days). CONCLUSION: There has been a dramatic increase in ECMO use for the treatment of ARDS in the United States. PMID- 26893317 TI - Admission to the Intensive Care Unit is Associated With Changes in the Oral Mycobiome. AB - A prospective exploratory study was conducted to characterize the oral mycobiome at baseline and determine whether changes occur after admission to the intensive care unit (ICU). We found that ICU admission is associated with alterations in the oral mycobiome, including an overall increase in Candida albicans. PMID- 26893311 TI - Inhaled corticosteroids and the increased risk of pneumonia: what's new? A 2015 updated review. AB - There is a considerable amount of evidence that supports the possibility of an increased risk of pneumonia associated with prolonged use of inhaled corticosteroids (ICS) in patients with chronic obstructive pulmonary disease (COPD). However, as yet, no statistically significant increase in pneumonia related 30-day mortality in patients on ICS has been demonstrated. The lack of objective pneumonia definitions and radiological confirmations have been a major source of bias, because of the similarities in clinical presentation between pneumonia and acute exacerbations of COPD. One of the newer fluticasone furoate studies overcomes these limitations and also provides an assessment of a range of doses, suggesting that the therapeutic window is quite narrow and that conventional dosing has probably been too high, although the absolute risk may be different compared to other drugs. Newer studies were not able to rule out budesonide as responsible for pneumonia, as previous evidence suggested, and there is still need for evidence from head-to-head comparisons in order to better assess possible intra-class differences. Although the exact mechanisms by which ICS increase the risk of pneumonia are not fully understood, the immunosuppressive effects of ICS on the respiratory epithelium and the disruption of the lung microbiome are most likely to be implicated. Given that COPD represents such a complex and heterogeneous disease, attempts are being made to identify clinical phenotypes with clear therapeutic implications, in order to optimize the pharmacological treatment of COPD and avoid the indiscriminate use of ICS. If deemed necessary, gradual withdrawal of ICS appears to be well tolerated. Vaccination against pneumococcus and influenza should be emphasized in patients with COPD receiving ICS. Physicians should keep in mind that signs and symptoms of pneumonia in COPD patients may be initially indistinguishable from those of an exacerbation, and that patients with COPD appear to be at increased risk of developing pneumonia as a complication of ICS therapy. PMID- 26893319 TI - Mayo Registry for Telemetry Efficacy in Arrest Study: An Assessment of the Utility of Telemetry in Predicting Clinical Decompensation. AB - INTRODUCTION: Our study assesses the utility of telemetry in identifying decompensation in patients with documented cardiopulmonary arrest. METHODS: A retrospective review of inpatients who experienced a cardiopulmonary arrest from May 1, 2008, until June 30, 2014, was performed. Telemetry records 24 hours prior to and immediately preceding cardiopulmonary arrest were reviewed. Patient subanalyses based on clinical demographics were made as well as analyses of survival comparing patients with identifiable rhythm changes in telemetry to those without. RESULTS: Of 242 patients included in the study, 75 (31.0%) and 110 (45.5%) experienced telemetry changes at the 24-hour and immediately preceding time periods, respectively. Of the telemetry changes, the majority were classified as nonmalignant (n = 50, 66.7% and n = 66, 55.5% at 24 hours prior and immediately preceding, respectively). There was no difference in telemetry changes between intensive care unit (ICU) and non-ICU patients and among patients stratified according to the American Heart Association telemetry indications. There was no difference in survival when comparing patients with telemetry changes immediately preceding and at 24 hours prior to an event (n = 30, 27.3% and n = 15, 20.0%) to those without telemetry changes during the same periods (n = 27, 20.5% and n = 42, 25.2%; P = .22 and .39). CONCLUSION: Telemetry has limited utility in predicting clinical decompensation in the inpatient setting. PMID- 26893321 TI - Bluetongue: Defra warns of risk to the UK later this year. PMID- 26893320 TI - Recruiting African Americans with peripheral artery disease for a behavioral intervention trial. AB - We report recruitment strategies for an NIH-funded trial focused on African Americans with peripheral artery disease (PAD). We present complete recruitment efforts for this 1-year trial, 5-year study. Eligibility included the following: African American, a resting ankle-brachial index (ABI) ? 0.99, a short physical performance battery (SPPB) score of 10 or lower, English speaking, telephone access, and absence of coronary ischemia during a submaximal treadmill test. Recruitment included mailings of brochures to zip codes in which more than 50% of residents were African American, advertisements, community events, and physician/clinic referrals. We telephone-screened 3511 persons, of whom 792 did not recall the method by which they learned about the study. We randomized 174 participants. Mailings yielded the highest percentage of randomized participants (n=60, 34.4%), followed by television advertisements (n=42, 24.1%), followed by community events (n=24, 13.8%). In conclusion, to recruit African Americans with PAD for a clinical trial, investigators should consider mailings of brochures, television advertisements, and community events. CLINICALTRIALSGOV IDENTIFIER NCT01321086. PMID- 26893322 TI - Evidence of colistin resistance in the EU 'worrying'--ECDC. PMID- 26893324 TI - Research awards to help accelerate control and eradication of bovine TB. PMID- 26893325 TI - Vet suspended from the Register after admitting dishonest conduct. PMID- 26893326 TI - WHO recommends against bringing ketamine under international control. PMID- 26893329 TI - Support for rabies control and prevention in Africa. PMID- 26893331 TI - Working together on developing veterinary vaccines. AB - Suzanne Jarvis reports from the recent conference of the Veterinary Vaccinology Network, which brought together more than 100 delegates to consider some of the successes in vaccine development, as well as the challenges ahead. PMID- 26893332 TI - Coalition aims to increase availability of fish medicines. PMID- 26893333 TI - Assessing the fitness of equids for transport. PMID- 26893334 TI - Summary of suspected adverse events, 2014. AB - The following article has been produced by the pharmacovigilance unit at the Veterinary Medicines Directorate (VMD) to provide a summary of some of the results from its surveillance work carried out in 2014. PMID- 26893335 TI - Measuring body temperature: how do different sites compare? PMID- 26893336 TI - Wild animal welfare. PMID- 26893337 TI - Reducing the risk of copper toxicity in dairy cattle. PMID- 26893338 TI - Acquired Fanconi-like syndrome cases associated with dried chicken and duck meat ingestion. PMID- 26893339 TI - Passion for poultry. AB - William Garton's interest in poultry began when he was a boy. Despite trying many aspects of veterinary medicine as a student, it was poultry-specific work that he enjoyed most. As a poultry intern with the Minster Veterinary Practice he wrote a monthly blog for Vet Record Careers, and he is now associate poultry director for the practice's north-west branches. PMID- 26893340 TI - Drosophila astrocytes cover specific territories of the CNS neuropil and are instructed to differentiate by Prospero, a key effector of Notch. AB - Astrocytes are crucial in the formation, fine-tuning, function and plasticity of neural circuits in the central nervous system. However, important questions remain about the mechanisms instructing astrocyte cell fate. We have studied astrogenesis in the ventral nerve cord of Drosophila larvae, where astrocytes exhibit remarkable morphological and molecular similarities to those in mammals. We reveal the births of larval astrocytes from a multipotent glial lineage, their allocation to reproducible positions, and their deployment of ramified arbors to cover specific neuropil territories to form a stereotyped astroglial map. Finally, we unraveled a molecular pathway for astrocyte differentiation in which the Ets protein Pointed and the Notch signaling pathway are required for astrogenesis; however, only Notch is sufficient to direct non-astrocytic progenitors toward astrocytic fate. We found that Prospero is a key effector of Notch in this process. Our data identify an instructive astrogenic program that acts as a binary switch to distinguish astrocytes from other glial cells. PMID- 26893341 TI - G2 phase arrest prevents bristle progenitor self-renewal and synchronizes cell division with cell fate differentiation. AB - Developmentally regulated cell cycle arrest is a fundamental feature of neurogenesis, whose significance is poorly understood. During Drosophila sensory organ (SO) development, primary progenitor (pI) cells arrest in G2 phase for precisely defined periods. Upon re-entering the cell cycle in response to developmental signals, these G2-arrested precursor cells divide and generate specialized neuronal and non-neuronal cells. To study how G2 phase arrest affects SO lineage specification, we forced pI cells to divide prematurely. This produced SOs with normal neuronal lineages but supernumerary non-neuronal cell types because prematurely dividing pI cells generate a secondary pI cell that produces a complete SO and an external precursor cell that undergoes amplification divisions. pI cells are therefore able to undergo self-renewal before transit to a terminal mode of division. Regulation of G2 phase arrest thus serves a dual role in SO development: preventing progenitor self-renewal and synchronizing cell division with developmental signals. Cell cycle arrest in G2 phase temporally coordinates the precursor cell proliferation potential with terminal cell fate determination to ensure formation of organs with a normal set of sensory cells. PMID- 26893343 TI - Reelin and cofilin cooperate during the migration of cortical neurons: a quantitative morphological analysis. AB - In reeler mutant mice, which are deficient in reelin (Reln), the lamination of the cerebral cortex is disrupted. Reelin signaling induces phosphorylation of LIM kinase 1, which phosphorylates the actin-depolymerizing protein cofilin in migrating neurons. Conditional cofilin mutants show neuronal migration defects. Thus, both reelin and cofilin are indispensable during cortical development. To analyze the effects of cofilin phosphorylation on neuronal migration we used in utero electroporation to transfect E14.5 wild-type cortical neurons with pCAG EGFP plasmids encoding either a nonphosphorylatable form of cofilin 1 (cofilin(S3A)), a pseudophosphorylated form (cofilin(S3E)) or wild-type cofilin 1 (cofilin(WT)). Wild-type controls and reeler neurons were transfected with pCAG EGFP. Real-time microscopy and histological analyses revealed that overexpression of cofilin(WT) and both phosphomutants induced migration defects and morphological abnormalities of cortical neurons. Of note, reeler neurons and cofilin(S3A)- and cofilin(S3E)-transfected neurons showed aberrant backward migration towards the ventricular zone. Overexpression of cofilin(S3E), the pseudophosphorylated form, partially rescued the migration defect of reeler neurons, as did overexpression of Limk1. Collectively, the results indicate that reelin and cofilin cooperate in controlling cytoskeletal dynamics during neuronal migration. PMID- 26893344 TI - Control of patterns of symmetric cell division in the epidermal and cortical tissues of the Arabidopsis root. AB - Controlled cell division is central to the growth and development of all multicellular organisms. Within the proliferating zone of the Arabidopsis root, regular symmetric divisions give rise to patterns of parallel files of cells, the genetic basis of which remains unclear. We found that genotypes impaired in the TONNEAU1a (TON1a) gene display misoriented symmetric divisions in the epidermis and have no division defects in the underlying cortical tissue. The TON1a gene encodes a microtubule-associated protein. We show that in the ton1a mutant, epidermal and cortical cells do not form narrow, ring-like preprophase bands (PPBs), which are plant-specific, cytoskeletal structures that predict the position of the division plane before mitosis. The results indicate that in the cortex but not in the epidermis, division plane positioning and patterning can proceed correctly in the absence of both a functional TON1a and PPB formation. Differences between tissues in how they respond to the signals that guide symmetric division orientation during patterning might provide the basis for organised organ growth in the absence of cell movements. PMID- 26893342 TI - Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish. AB - Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye. PMID- 26893347 TI - GATA4 regulates Fgf16 to promote heart repair after injury. AB - Although the mammalian heart can regenerate during the neonatal stage, this endogenous regenerative capacity is lost with age. Importantly, replication of cardiomyocytes has been found to be the key mechanism responsible for neonatal cardiac regeneration. Unraveling the transcriptional regulatory network for inducing cardiomyocyte replication will, therefore, be crucial for the development of novel therapies to drive cardiac repair after injury. Here, we investigated whether the key cardiac transcription factor GATA4 is required for neonatal mouse heart regeneration. Using the neonatal mouse heart cryoinjury and apical resection models with an inducible loss of GATA4 specifically in cardiomyocytes, we found severely depressed ventricular function in the Gata4 ablated mice (mutant) after injury. This was accompanied by reduced cardiomyocyte replication. In addition, the mutant hearts displayed impaired coronary angiogenesis and increased hypertrophy and fibrosis after injury. Mechanistically, we found that the paracrine factor FGF16 was significantly reduced in the mutant hearts after injury compared with littermate controls and was directly regulated by GATA4. Cardiac-specific overexpression of FGF16 via adeno-associated virus subtype 9 (AAV9) in the mutant hearts partially rescued the cryoinjury-induced cardiac hypertrophy, promoted cardiomyocyte replication and improved heart function after injury. Altogether, our data demonstrate that GATA4 is required for neonatal heart regeneration through regulation of Fgf16, suggesting that paracrine factors could be of potential use in promoting myocardial repair. PMID- 26893346 TI - Progressive developmental restriction, acquisition of left-right identity and cell growth behavior during lobe formation in mouse liver development. AB - To identify cell-based decisions implicated in morphogenesis of the mammalian liver, we performed clonal analysis of hepatocytes/hepatoblasts in mouse liver development, using a knock-in allele of Hnf4a/laacZ This transgene randomly undergoes a low frequency of recombination that generates a functional lacZ gene that produces beta-galactosidase in tissues in which Hnf4a is expressed. Two types of beta-galactosidase-positive clones were found. Most have undergone three to eight cell divisions and result from independent events (Luria-Delbruck fluctuation test); we calculate that they arose between E8.5 and E13.5. A second class was mega-clones derived from early endoderm progenitors, generating many descendants. Some originated from multi-potential founder cells, with labeled cells in the liver, pancreas and/or intestine. A few mega-clones populate only one side of the liver, indicating hepatic cell chirality. The patterns of labeled cells indicate cohesive and often oriented growth, notably in broad radial stripes, potentially implicated in the formation of liver lobes. This retrospective clonal analysis gives novel insights into clonal origins, cell behavior of progenitors and distinct properties of endoderm cells that underlie the formation and morphogenesis of the liver. PMID- 26893348 TI - Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila. AB - The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. PMID- 26893349 TI - 20-Hydroxyecdysone activates Forkhead box O to promote proteolysis during Helicoverpa armigera molting. AB - Insulin inhibits transcription factor Forkhead box O (FoxO) activity, and the steroid hormone 20-hydroxyecdysone (20E) activates FoxO; however, the mechanism is unclear. We hypothesized that 20E upregulates phosphatidylinositol-3,4,5 trisphosphate 3-phosphatase (PTEN) expression to activate FoxO, thereby promoting proteolysis during molting in the lepidopteran insect Helicoverpa armigera. FoxO expression is increased during molting and metamorphosis. The knockdown of FoxO in fifth instar larvae results in larval molting failure. 20E inhibits FoxO phosphorylation, resulting in FoxO nuclear translocation. Insulin, via Akt, induces FoxO phosphorylation and cytoplasmic localization. 20E represses insulin induced Akt phosphorylation and FoxO phosphorylation. 20E, via ecdysone receptor B1 (EcRB1) and the ultraspiracle protein (USP1), upregulates PTEN expression, which represses Akt phosphorylation, thereby repressing FoxO phosphorylation. The non-phosphorylated FoxO enters the nucleus and attaches to a FoxO-binding element in the upstream region of the Broad isoform 7 (BrZ7) gene to regulate BrZ7 transcription under 20E induction. 20E upregulates FoxO expression via EcRB1 and USP1. FoxO regulation of BrZ7 expression regulates Carboxypeptidase A expression for final proteolysis during insect molting. Hence, 20E activates FoxO via upregulating PTEN expression to counteract insulin activity and promote proteolysis. PMID- 26893345 TI - Split top: a maternal cathepsin B that regulates dorsoventral patterning and morphogenesis. AB - The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning. PMID- 26893351 TI - The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis. AB - An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARgamma, C/EBPalpha and MEST. We further show that SOX6 interacts with beta-catenin in adipocytes, suggesting an inhibition of WNT/beta catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms. PMID- 26893350 TI - Wnt/beta-catenin signaling enables developmental transitions during valvulogenesis. AB - Heart valve development proceeds through coordinated steps by which endocardial cushions (ECs) form thin, elongated and stratified valves. Wnt signaling and its canonical effector beta-catenin are proposed to contribute to endocardial-to mesenchymal transformation (EMT) through postnatal steps of valvulogenesis. However, genetic redundancy and lethality have made it challenging to define specific roles of the canonical Wnt pathway at different stages of valve formation. We developed a transgenic mouse system that provides spatiotemporal inhibition of Wnt/beta-catenin signaling by chemically inducible overexpression of Dkk1. Unexpectedly, this approach indicates canonical Wnt signaling is required for EMT in the proximal outflow tract (pOFT) but not atrioventricular canal (AVC) cushions. Furthermore, Wnt indirectly promotes pOFT EMT through its earlier activity in neighboring myocardial cells or their progenitors. Subsequently, Wnt/beta-catenin signaling is activated in cushion mesenchymal cells where it supports FGF-driven expansion of ECs and then AVC valve extracellular matrix patterning. Mice lacking Axin2, a negative Wnt regulator, have larger valves, suggesting that accumulating Axin2 in maturing valves represents negative feedback that restrains tissue overgrowth rather than simply reporting Wnt activity. Disruption of these Wnt/beta-catenin signaling roles that enable developmental transitions during valvulogenesis could account for common congenital valve defects. PMID- 26893352 TI - The ciliary marginal zone of the zebrafish retina: clonal and time-lapse analysis of a continuously growing tissue. AB - Clonal analysis is helping us understand the dynamics of cell replacement in homeostatic adult tissues (Simons and Clevers, 2011). Such an analysis, however, has not yet been achieved for continuously growing adult tissues, but is essential if we wish to understand the architecture of adult organs. The retinas of lower vertebrates grow throughout life from retinal stem cells (RSCs) and retinal progenitor cells (RPCs) at the rim of the retina, called the ciliary marginal zone (CMZ). Here, we show that RSCs reside in a niche at the extreme periphery of the CMZ and divide asymmetrically along a radial (peripheral to central) axis, leaving one daughter in the peripheral RSC niche and the other more central where it becomes an RPC. We also show that RPCs of the CMZ have clonal sizes and compositions that are statistically similar to progenitor cells of the embryonic retina and fit the same stochastic model of proliferation. These results link embryonic and postembryonic cell behaviour, and help to explain the constancy of tissue architecture that has been generated over a lifetime. PMID- 26893353 TI - Identification of a small-molecule ligand of the epigenetic reader protein Spindlin1 via a versatile screening platform. AB - Epigenetic modifications of histone tails play an essential role in the regulation of eukaryotic transcription. Writer and eraser enzymes establish and maintain the epigenetic code by creating or removing posttranslational marks. Specific binding proteins, called readers, recognize the modifications and mediate epigenetic signalling. Here, we present a versatile assay platform for the investigation of the interaction between methyl lysine readers and their ligands. This can be utilized for the screening of small-molecule inhibitors of such protein-protein interactions and the detailed characterization of the inhibition. Our platform is constructed in a modular way consisting of orthogonal in vitro binding assays for ligand screening and verification of initial hits and biophysical, label-free techniques for further kinetic characterization of confirmed ligands. A stability assay for the investigation of target engagement in a cellular context complements the platform. We applied the complete evaluation chain to the Tudor domain containing protein Spindlin1 and established the in vitro test systems for the double Tudor domain of the histone demethylase JMJD2C. We finally conducted an exploratory screen for inhibitors of the interaction between Spindlin1 and H3K4me3 and identified A366 as the first nanomolar small-molecule ligand of a Tudor domain containing methyl lysine reader. PMID- 26893355 TI - Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster. AB - The relationships of higher order chromatin organization to mammalian gene expression remain incompletely defined. The human Growth Hormone (hGH) multigene cluster contains five gene paralogs. These genes are selectively activated in either the pituitary or the placenta by distinct components of a remote locus control region (LCR). Prior studies have revealed that appropriate activation of the placental genes is dependent not only on the actions of the LCR, but also on the multigene composition of the cluster itself. Here, we demonstrate that the hGH LCR 'loops' over a distance of 28 kb in primary placental nuclei to make specific contacts with the promoters of the two GH genes in the cluster. This long-range interaction sequesters the GH genes from the three hCS genes which co assemble into a tightly packed 'hCS chromatin hub'. Elimination of the long-range looping, via specific deletion of the placental LCR components, triggers a dramatic disruption of the hCS chromatin hub. These data reveal a higher-order structural pathway by which long-range looping from an LCR impacts on local chromatin architecture that is linked to tissue-specific gene regulation within a multigene cluster. PMID- 26893354 TI - Categorical spectral analysis of periodicity in nucleosomal DNA. AB - DNA helical twist imposes geometric constraints on the location of histone-DNA interaction sites along nucleosomal DNA. Certain 10.5-bp periodic nucleotides in phase with these geometric constraints have been suggested to facilitate nucleosome positioning. However, the extent of nucleotide periodicity in nucleosomal DNA and its significance in directing nucleosome positioning still remain unclear. We clarify these issues by applying categorical spectral analysis to high-resolution nucleosome maps in two yeast species. We find that only a small fraction of nucleosomal sequences contain significant 10.5-bp periodicity. We further develop a spectral decomposition method to show that the previously observed periodicity in aligned nucleosomal sequences mainly results from proper phasing among nucleosomal sequences, and not from a preponderant occurrence of periodicity within individual sequences. Importantly, we show that this phasing may arise from the histones' proclivity for putting preferred nucleotides at some of the evenly spaced histone-DNA contact points with respect to the dyad axis. We demonstrate that 10.5-bp periodicity, when present, significantly facilitates rotational, but not translational, nucleosome positioning. Finally, although periodicity only moderately affects nucleosome occupancy genome wide, reduced periodicity is an evolutionarily conserved signature of nucleosome-depleted regions around transcription start/termination sites. PMID- 26893356 TI - Using intron position conservation for homology-based gene prediction. AB - Annotation of protein-coding genes is very important in bioinformatics and biology and has a decisive influence on many downstream analyses. Homology-based gene prediction programs allow for transferring knowledge about protein-coding genes from an annotated organism to an organism of interest.Here, we present a homology-based gene prediction program called GeMoMa. GeMoMa utilizes the conservation of intron positions within genes to predict related genes in other organisms. We assess the performance of GeMoMa and compare it with state-of-the art competitors on plant and animal genomes using an extended best reciprocal hit approach. We find that GeMoMa often makes more precise predictions than its competitors yielding a substantially increased number of correct transcripts. Subsequently, we exemplarily validate GeMoMa predictions using Sanger sequencing. Finally, we use RNA-seq data to compare the predictions of homology-based gene prediction programs, and find again that GeMoMa performs well.Hence, we conclude that exploiting intron position conservation improves homology-based gene prediction, and we make GeMoMa freely available as command-line tool and Galaxy integration. PMID- 26893357 TI - Lipopolysaccharide derived from the digestive tract activates inflammatory gene expression and inhibits casein synthesis in the mammary glands of lactating dairy cows. AB - To meet the nutrition requirements of lactation, dairy cows are usually fed a high concentrate diet (HC). However, high-grain feeding causes subacute ruminal acidosis (SARA), a metabolic disorder that causes milk protein depression. This study aimed to investigate the effect of lipopolysaccharide (LPS) released in the rumen on inflammatory gene expression and casein synthesis in mammary glands of lactating dairy cows fed a HC diet. We found that milk protein was significantly decreased in the HC group after 15 weeks of feeding. Overall, LPS concentrations in the rumen fluid, lacteal artery and vein were increased in the HC group. Transcriptome microarray was used to evaluate alterations in the signaling pathway in mammary glands. Signaling pathways involved in inflammatory responses were activated, whereas those involved in protein synthesis were inhibited in the HC group. mRNA expression involved in inflammatory responses, including that of TLR4, NF-kappaB and pro-inflammatory genes, was increased in the HC group, while alphas1-casein (CSN1S1), beta-casein (CSN2), mTOR and S6K gene expression were decreased. Moreover, protein expression was consistent with the corresponding gene expression. After feeding with an HC diet, LPS derived from the rumen increased inflammatory gene expression and inhibited casein synthesis in the mammary glands of lactating dairy cows fed a HC diet. PMID- 26893358 TI - DEPTOR suppresses the progression of esophageal squamous cell carcinoma and predicts poor prognosis. AB - As a naturally occurring inhibitor of mTOR, accumulated evidence has suggested that DEPTOR plays a pivotal role in suppressing the progression of human malignances. However, the function of DEPTOR in the development of esophageal squamous cell carcinoma (ESCC) is still unclear. Here we report that the expression of DEPTOR is significantly reduced in tumor tissues derived from human patients with ESCC, and the downregulation of DEPTOR predicts a poor prognosis of ESCC patients. In addition, we found that the expression of DEPTOR negatively regulates the tumorigenic activities of ESCC cell lines (KYSE150, KYSE510 and KYSE190). Furthermore, ectopic DEPTOR expression caused a significant suppression of the cellular proliferation, migration and invasion of KYSE150 cells, which has the lowest expression level of DEPTOR in the three cell lines. Meanwhile, CRISPR/Cas9 mediated knockout of DEPTOR in KYSE-510 cells significantly promoted cellular proliferation, migration and invasion. In addition, in vivo assays further revealed that tumor growth was significantly inhibited in xenografts with ectopic DEPTOR expression as compared to untreated KYSE150 cells, and was markedly enhanced in DEPTOR knockout KYSE-510 cells. Biochemical studies revealed that overexpression of DEPTOR led to the suppression of AKT/mTOR pathway as evidenced by reduced phosphorylation of AKT, mTOR and downstream SGK1, indicating DEPTOR might control the progression of ESCC through AKT/mTOR signaling pathway. Thus, these findings, for the first time, demonstrated that DEPTOR inhibits the tumorigenesis of ESCC cells and might serve as a potential therapeutic target or prognostic marker for human patients with ESCC. PMID- 26893359 TI - Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors. AB - Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ~80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets. PMID- 26893360 TI - BK K+ channel blockade inhibits radiation-induced migration/brain infiltration of glioblastoma cells. AB - Infiltration of the brain by glioblastoma cells reportedly requires Ca2+ signals and BK K+ channels that program and drive glioblastoma cell migration, respectively. Ionizing radiation (IR) has been shown to induce expression of the chemokine SDF-1, to alter the Ca2+ signaling, and to stimulate cell migration of glioblastoma cells. Here, we quantified fractionated IR-induced migration/brain infiltration of human glioblastoma cells in vitro and in an orthotopic mouse model and analyzed the role of SDF-1/CXCR4 signaling and BK channels. To this end, the radiation-induced migratory phenotypes of human T98G and far-red fluorescent U-87MG-Katushka glioblastoma cells were characterized by mRNA and protein expression, fura-2 Ca2+ imaging, BK patch-clamp recording and transfilter migration assay. In addition, U-87MG-Katushka cells were grown to solid glioblastomas in the right hemispheres of immunocompromised mice, fractionated irradiated (6 MV photons) with 5 * 0 or 5 * 2 Gy, and SDF-1, CXCR4, and BK protein expression by the tumor as well as glioblastoma brain infiltration was analyzed in dependence on BK channel targeting by systemic paxilline application concomitant to IR. As a result, IR stimulated SDF-1 signaling and induced migration of glioblastoma cells in vitro and in vivo. Importantly, paxilline blocked IR-induced migration in vivo. Collectively, our data demonstrate that fractionated IR of glioblastoma stimulates and BK K+ channel targeting mitigates migration and brain infiltration of glioblastoma cells in vivo. This suggests that BK channel targeting might represent a novel approach to overcome radiation induced spreading of malignant brain tumors during radiotherapy. PMID- 26893361 TI - Zinc finger protein ZBTB20 is an independent prognostic marker and promotes tumor growth of human hepatocellular carcinoma by repressing FoxO1. AB - Zinc finger and BTB domain-containing 20 (ZBTB20) is a new BTB/POZ-domain gene and a member of the POK family of transcriptional repressors. Notably, the role of ZBTB20 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In this study, the expression of ZBTB20 was significantly overexpressed in hepatocellular carcinoma (HCC) tissues. The positive expression of ZBTB20 was associated with large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Additionally, HCC patients with positive expression of ZBTB20 had a poorer 5-year survival. Multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. Gain- and loss-of-function experiments demonstrated that ZBTB20 promoted HCC cell viability, proliferation, tumorigenicity, and cell cycle progression. Mechanistically, Cyclin D1 and Cyclin E were increased, while p21 and p27 were decreased by ZBTB20 in HCC cells. FoxO1 was inversely correlated with ZBTB20 protein expression in the same cohort of HCC specimens. We further revealed that FoxO1 was transcriptionally repressed by ZBTB20 in HCC. Moreover, restoration of FoxO1 expression partially abrogated ZBTB20-induced HCC cell proliferation and growth entry in vitro and in vivo. Collectively, these results indicate that ZBTB20 may serve as a prognostic marker and promotes tumor growth of HCC via transcriptionally repressing FoxO1. PMID- 26893362 TI - RACK1 overexpression is linked to acquired imatinib resistance in gastrointestinal stromal tumor. AB - Although treatment with imatinib, which inhibits KIT and PDGFR, controls advanced disease in about 80% of gastrointestinal stromal tumor (GIST) patients, resistance to imatinib often develops. RACK1 (Receptor for Activated C Kinase 1) is a ribosomal protein that contributes to tumor progression by affecting proliferation, apoptosis, angiogenesis, and migration. Here, we found that c-KIT binds to RACK1 and increases proteasome-mediated RACK1 degradation. Imatinib treatment inhibits c-KIT activity and prevents RACK1 degradation, and RACK1 is upregulated in imatinib-resistant GIST cells compared to non-resistant parental cells. Moreover, Erk and Akt signaling were reactivated by imatinib in resistant GIST cells. RACK1 functioned as a scaffold protein and mediated Erk and Akt reactivation after imatinib treatment, thereby promoting GIST cell survival even in the presence of imatinib. Combined inhibition of KIT and RACK1 inhibited growth in imatinib-resistant GIST cell lines and reduced tumor relapse in GIST xenografts. These findings provide new insight into the role of RACK1 in imatinib resistance in GIST. PMID- 26893363 TI - mDia1 regulates breast cancer invasion by controlling membrane type 1-matrix metalloproteinase localization. AB - Mammalian diaphanous-related formin 1 (mDia1) expression has been linked with progression of malignant cancers in various tissues. However, the precise molecular mechanism underlying mDia1-mediated invasion in cancer cells has not been fully elucidated. In this study, we found that mDia1 is upregulated in invasive breast cancer cells. Knockdown of mDia1 in invasive breast cancer profoundly reduced invasive activity by controlling cellular localization of membrane type 1-matrix metalloproteinase (MT1-MMP) through interaction with microtubule tracks. Gene silencing and ectopic expression of the active form of mDia1 showed that mDia1 plays a key role in the intracellular trafficking of MT1 MMP to the plasma membrane through microtubules. We also demonstrated that highly invasive breast cancer cells possessed invasive activity in a 3D culture system, which was significantly reduced upon silencing mDia1 or MT1-MMP. Furthermore, mDia1-deficient cells cultured in 3D matrix showed impaired expression of the cancer stem cell marker genes, CD44 and CD133. Collectively, our findings suggest that regulation of cellular trafficking and microtubule-mediated localization of MT1-MMP by mDia1 is likely important in breast cancer invasion through the expression of cancer stem cell genes. PMID- 26893364 TI - PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma. AB - Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC. PMID- 26893365 TI - A genetic variation in microRNA target site of ETS2 is associated with clinical outcomes of paclitaxel-cisplatin chemotherapy in non-small cell lung cancer. AB - The present study was performed to investigate the association of single nucleotide polymorphisms (SNPs) located in the miRNA target sites with the clinical outcomes of first line paclitaxel-cisplatin chemotherapy in advanced NSCLC. Eighty SNPs in miRNA binding sites of cancer related genes selected from 18,500 miRNA:target bindings in crosslinking, ligation, and sequencing of hybrids (CLASH) data were investigated in 379 advanced NSCLC patients using a sequenom mass spectrometry-based genotype assay. qRT-PCR and luciferase assay were conducted to examine functional relevance of potentially functional SNPs in miRNA binding sites. Of the 80 SNPs analyzed, 16 SNPs were significantly associated with the clinical outcomes after chemotherapy. Among these, ANAPC1 rs3814026C>T, ETS2 rs461155A>G, SORBS1 rs7081076C>A and POLR2A rs2071504C>T could predict both chemotherapy response and survival. Notably, ETS2 rs461155A>G was significantly associated with decreased ETS2 mRNA expression in both tumor and paired normal lung tissues (Ptrend = 4 * 10-7, and 3 * 10-4, respectively). Consistently, a decreased expression of the reporter gene for the G allele of rs461155 compared with the A allele was observed by luciferase assay. These findings suggest that the four SNPs, especially ETS2 rs461155A>G, could be used as biomarkers predicting the clinical outcomes of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy. PMID- 26893366 TI - Early onset of hypertension and serum electrolyte changes as potential predictive factors of activity in advanced HCC patients treated with sorafenib: results from a retrospective analysis of the HCC-AVR group. AB - Hypertension (HTN) is frequently associated with the use of angiogenesis inhibitors targeting the vascular endothelial growth factor pathway and appears to be a generalized effect of this class of agent. We investigated the phenomenon in 61 patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib. Blood pressure and plasma electrolytes were measured on days 1 and 15 of the treatment. Patients with sorafenib-induced HTN had a better outcome than those without HTN (disease control rate: 63.4% vs. 17.2% (p=0.001); progression-free survival 6.0 months (95% CI 3.2-10.1) vs. 2.5 months (95% CI 1.9-2.6) (p<0.001) and overall survival 14.6 months (95% CI9.7-19.0) vs. 3.9 months (95% CI 3.1-8.7) (p=0.003). Sodium levels were generally higher on day 15 than at baseline (+2.38, p<0.0001) in the group of responders (+4.95, p <0.0001) compared to patients who progressed (PD) (+0.28, p=0.607). In contrast, potassium was lower on day 14 ( 0.30, p=0.0008) in the responder group (-0.58, p=0.003) than in those with progressive disease (-0.06, p=0.500). The early onset of hypertension is associated with improved clinical outcome in HCC patients treated with sorafenib. Our data are suggestive of an activation of the renin-angiotensin system in patients with advanced disease who developed HTN during sorafenib treatment. PMID- 26893367 TI - Podoplanin is a component of extracellular vesicles that reprograms cell-derived exosomal proteins and modulates lymphatic vessel formation. AB - Podoplanin (PDPN) is a transmembrane glycoprotein that plays crucial roles in embryonic development, the immune response, and malignant progression. Here, we report that cells ectopically or endogenously expressing PDPN release extracellular vesicles (EVs) that contain PDPN mRNA and protein. PDPN incorporates into membrane shed microvesicles (MVs) and endosomal-derived exosomes (EXOs), where it was found to colocalize with the canonical EV marker CD63 by immunoelectron microscopy. We have previously found that expression of PDPN in MDCK cells induces an epithelial-mesenchymal transition (EMT). Proteomic profiling of MDCK-PDPN cells compared to control cells shows that PDPN-induced EMT is associated with upregulation of oncogenic proteins and diminished expression of tumor suppressors. Proteomic analysis of exosomes reveals that MDCK PDPN EXOs were enriched in protein cargos involved in cell adhesion, cytoskeletal remodeling, signal transduction and, importantly, intracellular trafficking and EV biogenesis. Indeed, expression of PDPN in MDCK cells stimulated both EXO and MV production, while knockdown of endogenous PDPN in human HN5 squamous carcinoma cells reduced EXO production and inhibited tumorigenesis. EXOs released from MDCK PDPN and control cells both stimulated in vitro angiogenesis, but only EXOs containing PDPN were shown to promote lymphatic vessel formation. This effect was mediated by PDPN on the surface of EXOs, as demonstrated by a neutralizing specific monoclonal antibody. These results contribute to our understanding of PDPN-induced EMT in association to tumor progression, and suggest an important role for PDPN in EV biogenesis and/or release and for PDPN-EXOs in modulating lymphangiogenesis. PMID- 26893368 TI - Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens. AB - The calcium-sensing receptor is a G protein-coupled receptor that exerts cell type specific functions in numerous tissues and some cancers. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. We have now assessed cinacalcet, an allosteric activator of the CaSR approved for clinical use, as targeted therapy for this developmental tumor using neuroblastoma cell lines and patient-derived xenografts (PDX) with different MYCN and TP53 status. In vitro, acute exposure to cinacalcet induced endoplasmic reticulum stress coupled to apoptosis via ATF4-CHOP-TRB3 in CaSR positive, MYCN-amplified cells. Both phenotypes were partially abrogated by phospholipase C inhibitor U73122. Prolonged in vitro treatment also promoted dose and time-dependent apoptosis in CaSR-positive, MYCN-amplified cells and, irrespective of MYCN status, differentiation in surviving cells. Cinacalcet significantly inhibited tumor growth in MYCN-amplified xenografts and reduced that of MYCN-non amplified PDX. Morphology assessment showed fibrosis in MYCN amplified xenografts exposed to the drug. Microarrays analyses revealed up regulation of cancer-testis antigens (CTAs) in cinacalcet-treated MYCN-amplified tumors. These were predominantly CTAs encoded by genes mapping on chromosome X, which are the most immunogenic. Other modulated genes upon prolonged exposure to cinacalcet were involved in differentiation, cell cycle exit, microenvironment remodeling and calcium signaling pathways. CTAs were up-regulated in PDX and in vitro models as well. Moreover, progressive increase of CaSR expression upon cinacalcet treatment was seen both in vitro and in vivo. In summary, cinacalcet reduces neuroblastoma tumor growth and up-regulates CTAs. This effect represents a therapeutic opportunity and provides surrogate circulating markers of neuroblastoma response to this treatment. PMID- 26893369 TI - Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish. AB - Smooth muscle contraction is controlled by the regulated activity of the myosin heavy chain ATPase (Myh11). Myh11 mutations have diverse effects in the cardiovascular, digestive and genitourinary systems in humans and animal models. We previously reported a recessive missense mutation, meltdown (mlt), which converts a highly conserved tryptophan to arginine (W512R) in the rigid relay loop of zebrafish Myh11. The mlt mutation disrupts myosin regulation and non autonomously induces invasive expansion of the intestinal epithelium. Here, we report two newly identified missense mutations in the switch-1 (S237Y) and coil coiled (L1287M) domains of Myh11 that fail to complement mlt Cell invasion was not detected in either homozygous mutant but could be induced by oxidative stress and activation of oncogenic signaling pathways. The smooth muscle defect imparted by the mlt and S237Y mutations also delayed intestinal transit, and altered vascular function, as measured by blood flow in the dorsal aorta. The cell invasion phenotype induced by the three myh11 mutants correlated with the degree of myosin deregulation. These findings suggest that the vertebrate intestinal epithelium is tuned to the physical state of the surrounding stroma, which, in turn, governs its response to physiologic and pathologic stimuli. Genetic variants that alter the regulation of smooth muscle myosin might be risk factors for diseases affecting the intestine, vasculature, and other tissues that contain smooth muscle or contractile cells that express smooth muscle proteins, particularly in the setting of redox stress. PMID- 26893371 TI - Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A. AB - BACKGROUND/AIMS: Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. METHODS: LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. RESULTS: The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. CONCLUSIONS: The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer. PMID- 26893372 TI - Association between exhaled inflammatory markers and asthma control in children. AB - The relationship between exhaled inflammatory markers and asthma control in children is unclear. To explore the association between inflammatory markers in exhaled breath (fractional nitric oxide (FeNO), volatile organic compounds (VOCs), cytokines/chemokines) and asthma control. To assess whether exhaled inflammatory markers are able to discriminate between children with persistently controlled/uncontrolled asthma. 96 asthmatic children were followed-up in a one year observational study. Every 2 months, the following parameters were assessed: asthma control, FeNO, lung function (forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), exhaled VOCs, and cytokines/chemokines in exhaled breath condensate (EBC). Random Forest was used to analyse the relationship between exhaled inflammatory markers and asthma control. For each model, patients were randomly selected for a training set and validation set. To assess the accuracy of the classification models, receiver operating characteristic-curves (ROC-curves) were generated. No significant association was found between the exhaled inflammatory markers (FeNO, markers in EBC, VOCs) and asthma control (area under the ROC-curve 49%). However, 15 exhaled VOCs could discriminate between subgroups of children with persistently controlled and uncontrolled asthma during all clinical visits (area under the ROC-curve 86%). Adding FeNO and markers in EBC to this model, did not lead to a more accurate classification (area under the ROC-curve 87%). There was no association between exhaled inflammatory markers and asthma control in children. However, children with persistently controlled or uncontrolled asthma during the 12 month study period could be discriminated by a set of VOCs. PMID- 26893370 TI - Neurodegeneration in a Drosophila model of adrenoleukodystrophy: the roles of the Bubblegum and Double bubble acyl-CoA synthetases. AB - Debilitating neurodegenerative conditions with metabolic origins affect millions of individuals worldwide. Still, for most of these neurometabolic disorders there are neither cures nor disease-modifying therapies, and novel animal models are needed for elucidation of disease pathology and identification of potential therapeutic agents. To date, metabolic neurodegenerative disease has been modeled in animals with only limited success, in part because existing models constitute analyses of single mutants and have thus overlooked potential redundancy within metabolic gene pathways associated with disease. Here, we present the first analysis of a very-long-chain acyl-CoA synthetase (ACS) double mutant. We show that the Drosophila bubblegum(bgm) and double bubble(dbb) genes have overlapping functions, and that the consequences of double knockout of both bubblegum and double bubble in the fly brain are profound, affecting behavior and brain morphology, and providing the best paradigm to date for an animal model of adrenoleukodystrophy (ALD), a fatal childhood neurodegenerative disease associated with the accumulation of very-long-chain fatty acids. Using this more fully penetrant model of disease to interrogate brain morphology at the level of electron microscopy, we show that dysregulation of fatty acid metabolism via disruption of ACS function in vivois causal of neurodegenerative pathologies that are evident in both neuronal cells and their supporting cell populations, and leads ultimately to lytic cell death in affected areas of the brain. Finally, in an extension of our model system to the study of human disease, we describe our identification of an individual with leukodystrophy who harbors a rare mutation in SLC27a6(encoding a very-long-chain ACS), a human homolog of bgm and dbb. PMID- 26893373 TI - Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation. AB - OBJECTIVE: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion. METHODS: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items). RESULTS: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion. CONCLUSION: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response. PMID- 26893374 TI - Intracellular pH Modulates Autophagy and Mitophagy. AB - The specific autophagic elimination of mitochondria (mitophagy) plays the role of quality control for this organelle. Deregulation of mitophagy leads to an increased number of damaged mitochondria and triggers cell death. The deterioration of mitophagy has been hypothesized to underlie the pathogenesis of several neurodegenerative diseases, most notably Parkinson disease. Although some of the biochemical and molecular mechanisms of mitochondrial quality control are described in detail, physiological or pathological triggers of mitophagy are still not fully characterized. Here we show that the induction of mitophagy by the mitochondrial uncoupler FCCP is independent of the effect of mitochondrial membrane potential but dependent on acidification of the cytosol by FCCP. The ionophore nigericin also reduces cytosolic pH and induces PINK1/PARKIN-dependent and -independent mitophagy. The increase of intracellular pH with monensin suppresses the effects of FCCP and nigericin on mitochondrial degradation. Thus, a change in intracellular pH is a regulator of mitochondrial quality control. PMID- 26893375 TI - The Binding of Syndapin SH3 Domain to Dynamin Proline-rich Domain Involves Short and Long Distance Elements. AB - Dynamin is a GTPase that mediates vesicle fission during synaptic vesicle endocytosis. Its long C-terminal proline-rich domain contains 13 PXXP motifs, which orchestrate its interactions with multiple proteins. The SH3 domains of syndapin and endophilin bind the PXXP motifs called Site 2 and 3 (Pro-786-Pro 793) at the N-terminal end of the proline-rich domain, whereas the amphiphysin SH3 binds Site 9 (Pro-833-Pro-836) toward the C-terminal end. In some proteins, SH3/peptide interactions also involve short distance elements, which are 5-15 amino acid extensions flanking the central PXXP motif for high affinity binding. Here we found two previously unrecognized elements in the central and the C terminal end of the dynamin proline-rich domain that account for a significant increase in syndapin binding affinity compared with a previously reported Site 2 and Site 3 PXXP peptide alone. The first new element (Gly-807-Gly-811) is short distance element on the C-terminal side of Site 2 PXXP, which might contact a groove identified under the RT loop of the SH3 domain. The second element (Arg 838-Pro-844) is located about 50 amino acids downstream of Site 2. These two elements provide additional specificity to the syndapin SH3 domain outside of the well described polyproline-binding groove. Thus, the dynamin/syndapin interaction is mediated via a network of multiple contacts outside the core PXXP motif over a previously unrecognized extended region of the proline-rich domain. To our knowledge this is the first example among known SH3 interactions to involve spatially separated and extended long-range elements that combine to provide a higher affinity interaction. PMID- 26893376 TI - The Arf GTPase-activating Protein, ASAP1, Binds Nonmuscle Myosin 2A to Control Remodeling of the Actomyosin Network. AB - ASAP1 regulates F-actin-based structures and functions, including focal adhesions (FAs) and circular dorsal ruffles (CDRs), cell spreading and migration. ASAP1 function requires its N-terminal BAR domain. We discovered that nonmuscle myosin 2A (NM2A) directly bound the BAR-PH tandem of ASAP1in vitro ASAP1 and NM2A co immunoprecipitated and colocalized in cells. Knockdown of ASAP1 reduced colocalization of NM2A and F-actin in cells. Knockdown of ASAP1 or NM2A recapitulated each other's effects on FAs, cell migration, cell spreading, and CDRs. The NM2A-interacting BAR domain contributed to ASAP1 control of cell spreading and CDRs. Exogenous expression of NM2A rescued the effect of ASAP1 knockdown on CDRs but ASAP1 did not rescue NM2A knockdown defect in CDRs. Our results support the hypothesis that ASAP1 is a positive regulator of NM2A. Given other binding partners of ASAP1, ASAP1 may directly link signaling and the mechanical machinery of cell migration. PMID- 26893377 TI - The B3 Subunit of the Cone Cyclic Nucleotide-gated Channel Regulates the Light Responses of Cones and Contributes to the Channel Structural Flexibility. AB - Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2-3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3(-/-)/Nrl(-/-) mice with CNGB3 deficiency on a cone dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3(-/-)/Nrl(-/ ) mice compared with Nrl(-/-) mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. PMID- 26893380 TI - Outcomes of redo pulmonary valve replacement for bioprosthetic pulmonary valve failure in 61 patients with congenital heart disease. AB - OBJECTIVES: Although all bioprostheses used for pulmonary valve (PV) replacement (PVR) are prone to failure and will require redo PVR, data pertaining to the outcomes of this procedure are lacking. The objective of this study was to evaluate outcomes of redo PVR for bioprosthetic PV failure in patients with congenital heart disease. METHODS: A retrospective review of 61 patients who underwent redo PVR for bioprosthetic PV failure between November 1999 and June 2013 was performed. Univariable analyses were used to identify the factors associated with postoperative adverse events (PAEs). RESULTS: The median age at initial PVR was 7.0 years (1.6-36.5 years) and the median age at redo PVR was 13.5 years (7.6-43.3 years). Fundamental diagnoses were tetralogy of Fallot (n = 20), pulmonary atresia with ventricular septal defect (n = 20), double outlet right ventricle (n = 7) and others (n = 14). The median valve size was 25 mm (18 28 mm). There were 2 hospital deaths (3.3%). Eighteen patients (29.5%) experienced PAEs. PAEs were associated with higher preoperative right ventricular systolic pressure (105 +/- 22 vs 89 +/- 19 mmHg, P = 0.016) and longer cardiopulmonary bypass time (219 +/- 77 vs 164 +/- 59 min, P = 0.007). Completeness of follow-up was 98.3% and the median duration of follow-up was 5.5 years (0.1-14.3 years). There were 3 late deaths. The actuarial survival rate at 10 years was 83.7 +/- 8.0%. Eleven patients underwent the second redo PVR during follow-up. The rate of freedom from the second redo PVR at 10 years was 58.8 +/- 11.9%. The rate of freedom from both PV reintervention and structural valve deterioration (SVD) at 10 years was 32.0 +/- 13.3%. CONCLUSIONS: A substantial number of the patients experienced mortality or morbidities after redo PVR. Higher preoperative right ventricular systolic pressure and longer cardiopulmonary bypass time were associated with PAEs. By 10 years after the redo PVR, approximately two-thirds of patients will require PV reintervention or manifest SVD. PMID- 26893379 TI - Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase. AB - The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites. PMID- 26893381 TI - Impact of time interval between donor brain death and cold preservation on long term outcome in lung transplantation. AB - OBJECTIVES: Brain death (BD) is associated with various systemic responses and a cascade of inflammatory reactions. It is still unknown how the time interval from BD to cold preservation (CP) affects outcome after lung transplantation (LTx). This report investigates the impact of the time interval from BD to CP on long term outcome in LTx. METHODS: We reviewed 250 consecutive recipients who underwent LTx at our institution between January 2000 and December 2011. In Group I (n = 212), the time interval from BD to CP was <24 h, and in Group II (n = 38) >24 h. Cox proportional hazard regression analysis was performed to determine the risk factors affecting survival. RESULTS: The median time from BD to CP was 18.6 h (range 9-65). The rate of postoperative complications was comparable (P = 0.8). The 30-day mortality rate was 7.5% in Group I and 0% in Group II. The 5-year survival rate was better in Group II [70% (95% CI: 48.5-83.8%)] than in Group I [66% (95% CI: 58.3-72.5%)] without statistical significance (P = 0.3). Intraoperative extracorporeal membrane oxygenation (ECMO) use was identified as a significant risk factor for survival [HR = 1.7, (95% CI: 1.1-2.6), P = 0.01]. CONCLUSION: In our cohort, the time interval from BD to CP had no impact on long term outcome after LTx. PMID- 26893378 TI - The Different Conformational States of Tissue Transglutaminase Have Opposing Affects on Cell Viability. AB - Tissue transglutaminase (tTG) is an acyltransferase/GTP-binding protein that contributes to the development of various diseases. In human cancer cells, tTG activates signaling pathways that promote cell growth and survival, whereas in other disorders (i.e. neurodegeneration), overexpression of tTG enhances cell death. Therefore, it is important to understand how tTG is differentially regulated and functioning to promote diametrically distinct cellular outcomes. Previous structural studies revealed that tTG adopts either a nucleotide-bound closed conformation or a transamidation-competent open conformation. Here we provide evidence showing that these different conformational states determine whether tTG promotes, or is detrimental to, cell survival, with the open conformation of the protein being responsible for inducing cell death. First, we demonstrate that a nucleotide binding-defective form of tTG, which has previously been shown to induce cell death, assumes an open conformation in solution as assessed by an enhanced sensitivity to trypsin digestion and by small angle x-ray scattering (SAXS) analysis. We next identify two pairs of intramolecular hydrogen bonds that, based on existing x-ray structures, are predicted to form between the most C-terminal beta-barrel domain and the catalytic core domain of tTG. By disrupting these hydrogen bonds, we are able to generate forms of tTG that constitutively assume an open conformation and induce apoptosis. These findings provide important insights into how tTG participates in the pathogenesis of neurodegenerative diseases, particularly with regard to the actions of a C terminal truncated form of tTG (TG-Short) that has been linked to such disorders and induces apoptosis by assuming an open-like conformation. PMID- 26893382 TI - The prognostic value of metastatic lymph node number and ratio in oesophageal squamous cell carcinoma patients with or without neoadjuvant chemoradiation. AB - OBJECTIVES: We aim to evaluate the prognostic value of metastatic lymph node number (MLN) and ratio (MLR) in oesophageal squamous cell carcinoma (OSCC) patients with or without neoadjuvant chemoradiation. METHODS: Two thousand one hundred and fifty-one OSCC patients receiving oesophagectomy with (n = 850) or without (n = 1301) neoadjuvant chemoradiation were included. The MLN was categorized into 0 (N0), 1-2 (N1), 3-6 (N2) and more than 7 (N3); the MLR was categorized into 0, 0-0.2 and >0.2. The prognostic value was evaluated with survival analysis using the Cox proportional hazards regression model and the Kaplan-Meier method. RESULTS: In patients without neoadjuvant chemoradiation, the 3-year overall survival rates were 54.8, 34.4, 21.8 and 6.5% with MLN = 0, 1-2, 3 6 and more than 7, respectively (P < 0.001). The 3-year overall survival rates were 54.7, 31.2 and 14.2% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). In patients with neoadjuvant chemoradiation, the 3-year overall survival rates were 49.0, 28.4, 12.5 and 0.0% with MLN = 0, 1-2, 3-6 and more than 7, respectively (P < 0.001). However, the survival curves of MLN = 3-6 and MLN >=7 overlapped on the Kaplan-Meier plots. In contrast, MLR demonstrated good ability to show the survival differences on the Kaplan-Meier plots. The 3-year overall survival rates were 48.9, 27.3 and 0.0% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). CONCLUSIONS: Both MLN and MLR were significant prognostic factors in OSCC patients regardless of neoadjuvant chemoradiation. But in patients with neoadjuvant chemoradiation, the survival rates were similar between ypN2 and ypN3 patients, suggesting that there was no necessity of separating patients into ypN2 and ypN3 stages. PMID- 26893384 TI - Laparoscopic surgical treatment of hepatic splenosis. A case report. AB - AIM: Isolated hepatic splenosis is a rare but possible condition in abdominal surgery. At radiological imaging liver splenosis mimics malignant or pathological condition of the liver; obtaining a certain diagnosis prior to surgery is difficult. For this reason, the patients undergo to unnecessary operation, with a laparotomy access. We report a case of suspicious liver mass removed laparoscopically and revealed as hepatic splenosis. CASE REPORT: A 31 years old man patient was admitted to our Institution because of upper chronic abdominal pain. Thirteen years before the recovery the patient was operated of splenectomy with laparotomic incision. Computerized Tomography and Magnetic Resonance demonstrated the presence of suspicious hepatic mass in the III segment. RESULTS: The mass has been radically excised with laparoscopic approach. Postoperative stay was good and patient was discharged seven day after the operation. At histological examination ectopic splenic tissue on liver surface was found (socalled splenosis). DISCUSSION AND CONCLUSION: Hepatic splenosis is not a rare condition and should be considered with the differential diagnosis especially in patients who had previous splenectomy and absence of liver cirrhosis. Laparoscopic exploration should always be preferred for the diagnosis of uncertain liver mass. Few works report laparoscopic excision for liver splenosis. For experience at our Institution laparoscopic procedure has an important role to get the diagnosis and it is also a feasible approach for minimally invasive resection. KEY WORDS: Laparoscopy, Liver, Splenosis. PMID- 26893386 TI - Research challenges in palliative and end of life care. PMID- 26893383 TI - Structural Basis of the Interaction between Tuberous Sclerosis Complex 1 (TSC1) and Tre2-Bub2-Cdc16 Domain Family Member 7 (TBC1D7). AB - Mutations in TSC1 or TSC2 cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by the occurrence of benign tumors in various vital organs and tissues. TSC1 and TSC2, the TSC1 and TSC2 gene products, form the TSC protein complex that senses specific cellular growth conditions to control mTORC1 signaling. TBC1D7 is the third subunit of the TSC complex, and helps to stabilize the TSC1-TSC2 complex through its direct interaction with TSC1. Homozygous inactivation of TBC1D7 causes intellectual disability and megaencephaly. Here we report the crystal structure of a TSC1-TBC1D7 complex and biochemical characterization of the TSC1-TBC1D7 interaction. TBC1D7 interacts with the C-terminal region of the predicted coiled-coil domain of TSC1. The TSC1 TBC1D7 interface is largely hydrophobic, involving the alpha4 helix of TBC1D7. Each TBC1D7 molecule interacts simultaneously with two parallel TSC1 helices from two TSC1 molecules, suggesting that TBC1D7 may stabilize the TSC complex by tethering the C-terminal ends of two TSC1 coiled-coils. PMID- 26893388 TI - Multilevel Exploratory Factor Analysis of the Feeling Word Checklist-24. AB - Emotional reactions are a vital part of the therapeutic relationship. The Feeling Word Checklist-24 (FWC-24) is an instrument asking the clinician (or the patient) to report to what degree he or she has experienced various feelings during a therapeutic interaction. The aim of this study was to assess the factor structure of the clinician-rated FWC-24 when taking dependencies in the data into account. The sample was deliberately heterogeneous and consisted of 4,443 ratings made by 101 psychotherapists working with different psychotherapy methods in relation to 191 patients of different ages, genders, and with different primary diagnoses. A random intercept-only model revealed large intraclass correlation coefficients at the therapist level, indicating that a multilevel analysis was warranted. A two level exploratory factor analysis with therapists as the between level and patients plus sessions as the within level was conducted. The items from FWC-24 were found to be best represented by four factors on the between level and four factors on the within level. The factor structures were largely similar on the two levels and were labeled Engaged, Inadequate, Relaxed, and Moved. The different factors explained different amounts of variance on different levels, indicating that some factors are more therapist dependent and some more patient dependent. PMID- 26893389 TI - The Youth Psychopathic Traits Inventory: A Bifactor Model, Dimensionality, and Measurement Invariance. AB - The current study examines a bifactor model for the Youth Psychopathic Traits Inventory (YPI) in a Dutch community sample of adolescents ( N = 2,874). The primary goal was to examine the latent structure of the YPI with a bifactor modeling approach. Furthermore, the study examines the dimensionality and measurement invariance of the YPI. Results show that a bifactor model at subscale level fits the YPI best. The general psychopathy factor influences the 10 subscales of the YPI strongly, indicating that the YPI seems to be rather unidimensional than multidimensional. Nevertheless, the dimensions still explain nearly one third of the variance found. Findings imply that the bifactor model of the YPI should be used when examining relations with outcome variables, with a focus on the total score of the YPI, while factor scores should be reported with caution. Furthermore, the bifactor model appears invariant for gender, age, and ethnic background. PMID- 26893390 TI - The cis-regulatory switchboard of pancreatic ductal cancer. PMID- 26893391 TI - Emancipation from transcriptional latency: unphosphorylated STAT5 as guardian of hematopoietic differentiation. PMID- 26893392 TI - Singer K, Fisher B. Studies on abnormal hemoglobins, VI: electrophoretic demonstration of type S (sickle cell) hemoglobin in erythrocytes incapable of showing the sickle cell phenomenon. Blood. 1953;8(3):270-275. PMID- 26893393 TI - Breast cancer and thrombosis: timing matters. PMID- 26893394 TI - Shooting the messenger (RNA) in B-cell lymphoma. PMID- 26893395 TI - Not only TKI! Targeting FLT3-ITD by autophagy. PMID- 26893396 TI - Platelet production: new players in the field. PMID- 26893397 TI - Might haplo "be the (better) match"? PMID- 26893399 TI - Flipping the Advanced Cardiac Life Support Classroom with Team-based Learning: Comparison of Cognitive Testing Performance for Medical Students at the University of California, Irvine, United States. AB - PURPOSE: It aimed to find if written test results improved for advanced cardiac life support (ACLS) taught in flipped classroom/team-based Learning (FC/TBL) vs. lecture-based (LB) control in University of California-Irvine School of Medicine, USA. METHODS: Medical students took 2010 ACLS with FC/TBL (2015), compared to 3 classes in LB (2012-14) format. There were 27.5 hours of instruction for FC/TBL model (TBL 10.5, podcasts 9, small-group simulation 8 hours), and 20 (12 lecture, simulation 8 hours) in LB. TBL covered 13 cardiac cases; LB had none. Seven simulation cases and didactic content were the same by lecture (2012-14) or podcast (2015) as was testing: 50 multiple-choice questions (MCQ), 20 rhythm matchings, and 7 fill-in clinical cases. RESULTS: 354 students took the course (259 [73.1%] in LB in 2012-14, and 95 [26.9%] in FC/TBL in 2015). Two of 3 tests (MCQ and fill-in) improved for FC/TBL. Overall, median scores increased from 93.5% (IQR 90.6, 95.4) to 95.1% (92.8, 96.7, P=0.0001). For the fill-in test: 94.1% for LB (89.6, 97.2) to 96.6% for FC/TBL (92.4, 99.20 P=0.0001). For MC: 88% for LB (84, 92) to 90% for FC/TBL (86, 94, P=0.0002). For the rhythm test: median 100% for both formats. More students failed 1 of 3 tests with LB vs. FC/TBL (24.7% vs. 14.7%), and 2 or 3 components (8.1% vs. 3.2%, P=0.006). Conversely, 82.1% passed all 3 with FC/TBL vs. 67.2% with LB (difference 14.9%, 95% CI 4.8 24.0%). CONCLUSION: A FC/TBL format for ACLS marginally improved written test results. PMID- 26893400 TI - Obesity and associated factors in youth with an autism spectrum disorder. AB - Weight status on children and youth with autism spectrum disorder is limited. We examined the prevalence of overweight/obesity in children and youth with autism spectrum disorder, and associations between weight status and range of factors. Children and youth with autism spectrum disorder aged 2-16 years (n = 208) and their parents participated in this study. Body mass index was calculated using the Centers for Disease Control and Prevention growth charts and the International Obesity Task Force body mass index cut-offs. The Autism Diagnostic Observation Schedule was administered. Parents completed questionnaires about socio-demographics, diagnosed comorbidities, sleep disturbances, social functioning and medication of youth with autism spectrum disorder. The prevalence of overweight/obesity in participants with autism spectrum disorder was 35%. One quarter of obese children and youth (25.6%) had obese parents. There was a significant association between children and youth's body mass index and maternal body mass index (r = 0.25, n = 199, p < 0.001). The gender and age, parental education, family income, ethnicity, autism spectrum disorder severity, social functioning, psychotropic and complementary medication use of children and youth with autism spectrum disorder were not statistically associated with their weight status. Findings suggest the need for clinical settings to monitor weight status of children and youth with autism spectrum disorder in a bid to manage or prevent overweight/obesity in this population. Incorporating a family system approach to influence health behaviours among children and youth with autism spectrum disorder especially for specific weight interventions is warranted and should be further explored. PMID- 26893401 TI - Strategies for implementing implementation science: a methodological overview. AB - A key reason for the consistent gaps between evidence and practice across all areas of medicine is that there has been little attempt to identify or target factors critical for successful implementation of an evidence-based intervention. There is either no explicit implementation strategy or the strategy is based on a best guess rather than on a systematic assessment of crucial barriers and enablers. A different approach is needed to close the evidence-practice gap and thereby achieve the triple aim of improved health, improved patient experience and reduced healthcare costs. We present three fundamental principles of implementation science, which is a methodology that offers a systematic and comprehensive approach to improving healthcare practice and a series of 'how to' steps to conduct implementation science research. In an accompanying article, a scoping review of the types of implementation science research conducted in emergency medicine is reviewed, and several of the principles related to this review are discussed. PMID- 26893402 TI - EGFR mutation detection on routine cytological smears of non-small cell lung cancer by digital PCR: a validation study. AB - Highly sensitive genotyping techniques are useful to detect epidermal growth factor receptor (EGFR) mutations on lung cancer cytological samples, when these specimens feature only few neoplastic cells. This study aimed to validate digital PCR (dPCR) methodology on cytological material. In plasmid model system, dPCR allowed for the detection of a minimal percentage (1%) of EGFR mutant alleles. Cytological samples (n = 30), with neoplastic cell percentage ranging from 10% to 80% and yielding a quantity of extracted DNA ranging from 1.75 to 60 ng/uL were selected. Results previously generated by fragment length and TaqMan assays (n = 8 exon 19 deletions, n = 2 L858R mutations and n = 20 wild-type DNA) were compared with those obtained by dPCR. Data were highly concordant (96.6%). However, dPCR detected an additional L858R mutation that had been missed by TaqMan assay on a paucicellular smear. This mutation was confirmed by cloning PCR products and sequencing. Thus, dPCR can reliably be used to increase EGFR mutation detection rate on scarcely cellular lung cancer smears. PMID- 26893403 TI - Illustrations reduce contamination of midstream urine samples in the emergency department. AB - AIMS: Urinalysis provides direction in diagnosis and treatment of patients in the emergency department (ED). Midstream urine (MSU) collection from female patients has a high contamination rate. Verbal instruction by nurses to patients reduces contamination but is inconsistent owing to lack of time and professional knowledge. This study aimed to determine if an alternative mode of instruction requiring minimal staff input may be effective. METHODS: A pseudorandomised controlled trial was undertaken with 240 female patients for whom urinalysis was clinically required. No change was made to normal practice with regards to verbal instruction. Prior to collecting their sample the intervention cohort received illustrated instruction on how to collect a clean uncontaminated MSU sample. The control cohort received no illustrated instruction. Compared outcomes were rate of contamination on urinalysis, defined as 10 or more epithelial cells per high power field, and answers to a structured patient questionnaire. RESULTS: Contamination rate was reduced from 40% to 25% by the intervention. According to patient survey responses, verbal collection instructions were seldom given and the actions of hand washing, cleaning with a towelette, and voiding then stopping were significantly higher in the intervention group. The illustrations were well received by over 95% of patients and were considered to be clear and effective especially for patients with reading difficulties and/or from a non-English speaking background. CONCLUSIONS: Illustrated urine collection instructions were well accepted by female ED patients, improved the rate of proper MSU collection and reduced the rate of urinalysis contamination in the ED. PMID- 26893404 TI - Primary Breast Lymphoma in a Woman: A Case Report and Review of the Literature. AB - BACKGROUND: Primary breast lymphoma (PBL) is an unusual clinical entity accounting for 0.4-0.5% of all breast neoplasms. The usual presentation includes a painless palpable mass similar to that of breast carcinoma. Diffuse large B cell lymphoma (DLBCL) is the most common identifiable type of PBL based on the histopathological examination. CASE REPORT: We report an unusual case of a 43 year-old Indonesian woman who presented with a 7-month history of a painless mass in the left breast. A core needle biopsy revealed diffuse infiltration of large atypical lymphoid cells. The immuno-histochemical biomarkers confirmed the diagnosis of a DLBCL. A bone scan showed no evidence of bone metastasis. It was treated non-surgically, based on the decision of the breast multidisciplinary team (MDT). The patient was treated with 4 cycles of combination chemotherapy with R-CODOX/IVAC. A follow-up PET scan revealed non-significant mild F-18 fluorodeoxyglucose (FDG) uptake at the periphery of the residual left breast mass, indicating a radiologically favorable response. CONCLUSIONS: Early and accurate diagnosis of PBL is crucial for selecting the appropriate MDT treatment strategies to avert potentially harmful surgical interventions. PMID- 26893405 TI - Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST). AB - BACKGROUND: Fibrinogen supplementation has been proposed both to prevent and treat postoperative bleeding in cardiac surgery. The optimal fibrinogen concentration trigger and target values and the fibrinogen concentrate dose required remain uncertain. This subanalysis of data from the Zero-Plasma Trial (ZEPLAST) assessed target fibrinogen values and the corresponding fibrinogen concentrate dose for supplementation. METHODS: We performed a post hoc analysis of 116 subjects included in the randomized, placebo-controlled ZEPLAST trail. Data considered were fibrin-based thromboelastometry (FIBTEM) maximum clot firmness (MCF) determined by whole-blood thromboelastometry (ROTEM) before and after placebo or fibrinogen concentrate, Clauss fibrinogen concentration after placebo or fibrinogen concentrate, postoperative bleeding and severe bleeding (SB). The association between FIBTEM MCF and Clauss fibrinogen concentration was tested with linear regression analyses. The predictive value for SB of FIBTEM MCF and Clauss fibrinogen concentration was tested with receiver operating characteristic analyses. RESULTS: There was a good association between FIBTEM MCF and Clauss fibrinogen concentration in the baseline study population (r(2) = 0.66), which worsened in fibrinogen-supplemented subjects. Both FIBTEM MCF and Clauss fibrinogen concentration yielded a good discriminative power for SB (area under the curve 0.721 and 0.767, respectively). The negative predictive value for SB was 100% for a Clauss fibrinogen concentration of 287 mg dl(-1) and 98% for an FIBTEM MCF of 14 mm. Based on these newly defined target values, the dose of fibrinogen concentrate needed would be 3 g lower than the dose used in ZEPLAST. CONCLUSIONS: A dose of fibrinogen concentrate rarely exceeding 2 g might be sufficient to prevent bleeding in cardiac surgery. PMID- 26893406 TI - Paediatric procedural sedation using ketamine in a UK emergency department: a 7 year review of practice. AB - BACKGROUND: Ketamine is growing in popularity for procedural sedation in the paediatric population, yet safety concerns remain. We performed a retrospective review of practice and outcomes of paediatric ketamine sedation using the World SIVA International Sedation Task Force reporting tool. METHODS: A retrospective inspection of the dedicated emergency department electronic sedation database and subsequent note and sedation chart review was performed for all paediatric sedations throughout a 7 yr period from September 2006. All adverse events were stratified. RESULTS: During the study period, procedural sedation was provided for a total of 243 children, of whom 215 were sedated with ketamine, most commonly for wound management (n=131). The median patient age was 4 yr (14 months to 15 yr), and 63.7% were male. Of the total, 76.7% were discharged home either directly (n=101) or after brief observation (n=64). One patient required subsequent general anaesthesia after a failed sedation with paradoxical agitation. Of the total, 9.8% of patients had an adverse event, the most severe risk stratification being 'minor risk'. All interventions were 'minimal risk'. There were no 'sentinel risk' outcomes. CONCLUSIONS: These data support the ongoing use of ketamine for paediatric procedural sedation in the emergency department by emergency physicians. Relatively high resource requirements mean that ensuring adequate numbers of procedures may prove challenging. PMID- 26893407 TI - Contemporary management of acute and chronic deep venous thrombosis. AB - INTRODUCTION: This review aims to provide an update on the management of deep vein thrombosis (DVT). SOURCES OF DATA: A systematic search of PubMed, Google Scholar and Cochrane databases was carried out. AREAS OF AGREEMENT: Direct oral anticoagulants (DOACs) are as effective and easier to use than vitamin K antagonists for the treatment of DVT. Catheter-directed thrombolysis can reduce post thrombotic syndrome in patients with iliofemoral DVT. Compression bandaging can help heal a venous ulcer. AREAS OF CONTROVERSY: Compression hosiery to prevent post thrombotic syndrome. Long-term evidence to show clinical benefit of using endovenous therapies to restore deep vein patency. GROWING POINTS: Developing imaging methods to identify patients who would benefit from venous thrombolysis. The evolution of dedicated venous stents. AREAS TIMELY FOR DEVELOPING RESEARCH: Understanding the mechanisms that lead to stent occlusion and investigation into the appropriate treatments that could prevent in-stent thrombosis is required. PMID- 26893408 TI - Draft Genome Sequence of Streptomyces silvensis ATCC 53525, a Producer of Novel Hormone Antagonists. AB - Streptomyces silvensis produces nonribosomal peptides that act as antagonists of the human oxytocin and vasopressin receptors. Here, we present the genome sequence of S. silvensis ATCC 53525 and demonstrate that this organism possesses a number of additional biosynthetic gene clusters and might be a promising source for genome-guided drug discovery efforts. PMID- 26893409 TI - Complete Genome Sequence of a Porcine Epidemic Diarrhea Virus Strain from Vietnam, HUA-14PED96, with a Large Genomic Deletion. AB - A highly virulent strain of Porcine epidemic diarrhea virus (PEDV) causing severe diarrhea has recently emerged in Vietnam. Genomic sequences from a novel strain, HUA-14PED96, isolated from a Vietnamese piglet with serious diarrhea show relatively high identity with U.S.-like PEDV strains, and have a 72-nt deletion in the open reading frame 1a (ORF1a) gene. PMID- 26893410 TI - Draft Genome Sequence of Shewanella sp. Strain P1-14-1, a Bacterial Inducer of Settlement and Morphogenesis in Larvae of the Marine Hydroid Hydractinia echinata. AB - The assembly and annotation of the draft genome sequence of Shewanella sp. strain P1-14-1 are reported here to investigate the genes responsible for interkingdom interactions, secondary metabolite production, and microbial electrogenesis. PMID- 26893411 TI - Genome Sequence of a Gram-Positive Diazotroph, Paenibacillus durus Type Strain ATCC 35681. AB - Here, we report the complete genome sequence of Paenibacillus durus type strain ATCC 35681, which can fix atmospheric nitrogen even in the presence of nitrate. PMID- 26893413 TI - Complete Genome Sequence of the Type Strain of Aeromonas schubertii, ATCC 43700. AB - We sequenced the complete genome of the type strain of Aeromonas schubertii, ATCC 43700. The full genome sequence of A. schubertii ATCC 43700 is 4,356,858 bp, which encodes 3,842 proteins and contains 110 predicted RNA genes. PMID- 26893412 TI - Draft Genome Sequences of Two Pseudoalteromonas Strains Isolated from Roots and Leaf Blades of the Seagrass Zostera marina. AB - Here, we present the draft genome sequences for Pseudoalteromonas sp. strain UCD 33C and Pseudoalteromonas lipolytica UCD-48B. Pseudoalteromonas sp. UCD-33C was isolated from Zostera marina roots and P. lipolytica UCD-48B from Z. marina leaf blades, both collected in Woods Hole, MA. These assemblies contain 4,479,285 bp and 4,592,435 bp, respectively. PMID- 26893414 TI - Draft Genome Sequence of the Photoheterotrophic Chloracidobacterium thermophilum Strain OC1 Found in a Mat at Ojo Caliente. AB - Metagenomics of an enrichment culture from a New Mexico hot spring allowed the description of a draft genome of a Chloracidobacterium thermophilum strain for the first time outside Yellowstone National Park with a surprisingly high degree of identity with the type strain. PMID- 26893415 TI - Draft Genome Sequence of a Thermophilic Cyanobacterium from the Family Oscillatoriales (Strain MTP1) from the Chalk River, Colorado. AB - The draft genome (57.7% GC, 7,647,882 bp) of the novel thermophilic cyanobacterium MTP1 was determined by metagenomics of an enrichment culture. The genome shows that it is in the family Oscillatoriales and encodes multiple heavy metal resistances as well as the capacity to make exopolysaccharides. PMID- 26893416 TI - Genome Sequences of Streptomyces Phages Amela and Verse. AB - Amela and Verse are two Streptomyces phages isolated by enrichment on Streptomyces venezuelae (ATCC 10712) from two different soil samples. Amela has a genome length of 49,452, with 75 genes. Verse has a genome length of 49,483, with 75 genes. Both belong to the BD3 subcluster of Actinobacteriophage. PMID- 26893417 TI - Draft Genome Sequences of Staphylococcus aureus Strains Isolated from Subclinical Bovine Mastitis in Brazil. AB - Here, we present the draft genome sequences of four Staphylococcus aureus strains isolated from mastitic milk collected from animals with subclinical manifestations. Three of them were typed as sequence type 126 (ST126), a genotype with no genome sequence available. ST126 is found in several herds of southern Brazil and is described as a bovine pathogen strongly associated with milk around the world. PMID- 26893418 TI - Draft Genome Sequence of Pantoea ananatis Strain AMG521, a Rice Plant Growth Promoting Bacterial Endophyte Isolated from the Guadalquivir Marshes in Southern Spain. AB - The rice endophyte Pantoea ananatis AMG521 shows several plant growth-promoting properties and promotes rice yield increases. Its draft genome was estimated at 4,891,568 bp with 4,704 coding sequences (CDS). The genome encodes genes for N acylhomoserine lactone (AHL) synthases, AHL hydrolases, hyperadherence (yidQ, yidP, and yidR), fusaric acid resistance, and oxidation of lignin, highlighting its biotechnological potential. PMID- 26893419 TI - High-Quality Draft Genome Sequence of Low-pH-Active Veillonella parvula Strain SHI-1, Isolated from Human Saliva within an In Vitro Oral Biofilm Model. AB - We announce here a draft genome sequence of Veillonella parvula strain SHI-1, obtained from healthy human saliva, discovered to be active at low pH using metatranscriptomics within an in vitro oral biofilm model. The genome is composed of 7 contigs, for a total of 2,200,064 bp. PMID- 26893420 TI - Draft Genome Sequence of Paenibacillus etheri sp. nov. SH7T, a Methyl Tert-Butyl Ether Degrader. AB - We report here the draft genome sequence of Paenibacillus etheri sp. nov. SH7(T) (= CECT 8558(T) = DSM 29760(T)), isolated from a hydrocarbon-contaminated soil pilot plant in Granada, Spain. The bacterium was isolated and sequenced due to its methyl tert-butyl ether (MTBE)-degrading properties. PMID- 26893421 TI - Draft Genome Sequence of Aspergillus niger Strain An76. AB - The filamentous fungus Aspergillus niger has become one of the most important fungi in industrial biotechnology, and it can efficiently secrete both polysaccharide-degrading enzymes and organic acids. We report here the 6,074,961,332-bp draft sequence of A. niger strain An76, and the findings provide important information related to its lignocellulose-degrading ability. PMID- 26893422 TI - Complete Chloroplast Genome Sequence and Annotation of the Tropical japonica Group of Asian Cultivated Rice (Oryza sativa L.). AB - We announce here the first complete chloroplast genome sequence of the tropical japonica rice, along with its genome structure and functional annotation. The plant was collected from Indonesia and deposited as a germplasm accession of the International Rice GenBank Collection (IRGC 66630) at the International Rice Research Institute (IRRI). This genome provides valuable data for the future utilization of the germplasm of rice. PMID- 26893423 TI - Draft Genome Sequence of Tepidimonas taiwanensis Strain MB2, a Chemolithotrophic Thermophile Isolated from a Hot Spring in Central India. AB - Tepidimonas taiwanensis strain MB2 is a thermophile isolated from a hot spring located in central India. Here, we report a 28,49,160 bp draft genome sequence of Tepidimonas taiwanensis MB2. The genome shows properties of sulfur metabolism, nitrogen fixation, ammonia metabolism, assimilation of organic acids, and a wide variety of proteases. PMID- 26893424 TI - Draft Genome Sequences of Two Novel Amoeba-Resistant Intranuclear Bacteria, "Candidatus Berkiella cookevillensis" and "Candidatus Berkiella aquae". AB - "Candidatus Berkiella cookevillensis" and "Candidatus Berkiella aquae" are obligate intranuclear endosymbionts of freshwater amoebae. Here, we present the draft genome sequences of these two bacteria, with total sizes of 2,990,361 bp and 3,626,027 bp, respectively. PMID- 26893425 TI - Draft Genome Sequence of "Candidatus Methanomethylophilus" sp. 1R26, Enriched from Bovine Rumen, a Methanogenic Archaeon Belonging to the Methanomassiliicoccales Order. AB - Here, we present the draft genome of "Candidatus Methanomethylophilus" sp. 1R26, a member of the newly described Methanomassiliicoccales order of Euryarcheaota. The enrichment culture was established from bovine rumen contents and produced methane from trimethylamine and methanol. The draft genome contains genes for methanogenesis from methylated compounds. PMID- 26893426 TI - Complete Genome Sequencing of Bovine Viral Diarrhea Virus 1, Subgenotypes 1n and 1o. AB - To gain further insight into the genomic features of bovine viral diarrhea virus 1 (BVDV-1) subgenotypes, we sequenced the complete genome of BVDV-1n Shitara/02/06 and BVDV-1o IS26NCP/01. The complete genome of Shitara/02/06 and IS26NCP/01 shared 77.7 to 79.3% and 78.0 to 85.7% sequence identities with other BVDV-1 subgenotype strains, respectively. PMID- 26893427 TI - Draft Genome Sequence of Type Strain Streptococcus gordonii ATCC 10558. AB - Streptococcus gordonii ATCC 10558(T) was isolated from a patient with infective endocarditis in 1946 and announced as a type strain in 1989. Here, we report the 2,154,510-bp draft genome sequence of S. gordonii ATCC 10558(T). This sequence will contribute to knowledge about the pathogenesis of infective endocarditis. PMID- 26893428 TI - Draft Whole-Genome Sequence of Trichoderma gamsii T6085, a Promising Biocontrol Agent of Fusarium Head Blight on Wheat. AB - Trichoderma gamsii T6085 is a promising beneficial isolate whose effects consist of growth inhibition of the main agents causing Fusarium head blight, reduction of mycotoxin accumulation, competition for wheat debris, and reduction of the disease in both the lab and the field. Here, we present the first genome assembly of a T. gamsii isolate, providing a useful platform for the scientific community. PMID- 26893429 TI - Characterization of a Salivirus (Picornaviridae) from a Diarrheal Child in Guatemala. AB - The complete genome sequence of a salivirus was identified in a stool sample from a Guatemalan child with acute gastroenteritis during a 2009 norovirus outbreak. This genome (genotype A1 strain GUT/2009/A-1746) shares 82% to 94% genome-wide nucleotide identity with saliviruses from the United States, China, Germany, and Nigeria, representing the first salivirus sequence from Central America. PMID- 26893431 TI - Draft Genome Sequence of Mycobacterium tuberculosis KT-0184, Isolated in South Korea. AB - Here, we describe the draft genome sequence of Mycobacterium tuberculosis KT 0184, from the Beijing family. This genome will provide insight into the evolution and adaptation of M. tuberculosis KT-0184 in human hosts. PMID- 26893432 TI - First Complete Genome Sequence of Tenacibaculum dicentrarchi, an Emerging Bacterial Pathogen of Salmonids. AB - Tenacibaculum-like bacilli have recently been isolated from diseased sea-reared Atlantic salmon in outbreaks that took place in the XI region (Region de Aysen) of Chile. Molecular typing identified the bacterium as Tenacibaculum dicentrarchi. Here, we report the complete genome sequence of the AY7486TD isolate recovered during those outbreaks. PMID- 26893430 TI - Complete Genome Sequence of Multidrug-Resistant Citrobacter freundii Strain P10159, Isolated from Urine Samples from a Patient with Esophageal Carcinoma. AB - Citrobacter freundii is an opportunistic pathogen that can cause diarrhea, septicemia, meningitis, and urinary tract infections. We report here the complete genome sequence of C. freundii strain P10159, isolated from urine samples from a patient in China with esophageal carcinoma. The genome has 5,080,321 bp and 4,768 coding sequences, with a G+C content of 51.7%. PMID- 26893433 TI - High-Quality Draft Genome Sequence of Leucobacter sp. Strain G161, a Distinct and Effective Chromium Reducer. AB - Here, we report the genome sequence for Leucobacter sp. strain G161 due to its distinct and effective hexavalent chromium reduction under aerobic growth conditions, followed by facultative anaerobic incubation. The draft genome sequence of Leucobacter sp. G161 comprises 3,554,188 bp, with an average G+C content of 65.3%, exhibiting 3,341 protein-coding genes and 55 predicted RNA genes. PMID- 26893434 TI - Complete Genome Sequence of Pseudomonas aeruginosa Phage-Resistant Variant PA1RG. AB - Bacteria have evolved several defense systems against phage predation. Here, we report the 6,500,439-bp complete genome sequence of the Pseudomonas aeruginosa phage-resistant variant PA1RG. Single-molecule real-time (SMRT) sequencing and de novo assembly revealed a single contig with 320-fold sequence coverage. PMID- 26893435 TI - Draft Genome Sequence of Flavobacterium psychrophilum Strain KTEN-1510 with Genotype A/G-C, Isolated from an Ayu (Plecoglossus altivelis altivelis) in the Kagami River, Kochi, Japan. AB - In this paper, we describe the draft genome sequence of Flavobacterium psychrophilum strain KTEN-1510, with genotype A/G-C. This strain was isolated in October 2015 from the gills of an ayu (Plecoglossus altivelis altivelis) in the upper Kagami River in central Kochi Prefecture on Shikoku Island, Japan. PMID- 26893436 TI - Draft Genome Sequences of Two Vibrio splendidus Strains, Isolated from Seagrass Sediment. AB - Here, we present the draft genome sequences of Vibrio splendidus UCD-SED7 and UCD SED10 (phylum Proteobacteria). These strains were isolated from sediment surrounding Zostera marina roots near the UC Davis Bodega Marine Laboratory (Bodega, Bay, California). These assemblies contain 5,334,236 bp and 5,904,824 bp, respectively. PMID- 26893437 TI - Complete Genome Sequence of a Chinese Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus That Has a Further Deletion in the Nsp2 Gene. AB - Here, we report the complete genome of a Chinese highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) characterized by a further 29-amino acid (87 nucleotides) deletion in its Nsp2-coding region compared to the prototype of the HP-PRRSV JXA1 strain. PMID- 26893438 TI - Draft Genome Sequence of Acinetobacter johnsonii MB44, Exhibiting Nematicidal Activity against Caenorhabditis elegans. AB - Acinetobacter johnsonii MB44 was isolated from a frost-plant-tissue sample, which showed noteworthy nematicidal activity against the model organism Caenorhabditis elegans. Here, we report the 3.4 Mb draft genome of A. johnsonii MB44, which will help in understanding the molecular mechanism of its ability to infect nematodes. PMID- 26893440 TI - Testosterone may improve sexual function and mood in older men with low levels. PMID- 26893439 TI - Interaction Between Polymorphisms of IFN-gamma and MICA Correlated with Hepatocellular Carcinoma. AB - BACKGROUND We explored the relationship of interferon-gamma (IFN-gamma) and MHC class-I chain related gene A (MICA) genes polymorphisms with hepatocellular carcinoma (HCC) risk, and tried to determine whether the interaction existed between these two genes polymorphisms on the basis of HCC. MATERIAL AND METHODS Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect the genotypes of the 3 single-nucleotide polymorphisms (SNPs) and to analyze the correlation of each SNP with HCC susceptibility in 120 HCC patients and 124 healthy people. The association strength between the 3 SNPs and HCC is represented with odds ratio (OR) and 95% confidence interval (95% CI). Hardy-Weinberg equilibrium (HWE) was tested by chi2 test in the control group. RESULTS GG genotype of IFN-gamma rs2069727 polymorphism had apparently different distributions in case and control groups (P<0.05), and might confer increased risk of HCC (OR=3.40, 95%CI=1.23-9.38). Analysis of MICA rs2596542 polymorphism also yielded the same result (OR=2.90, 95%CI=1.10-7.67), as did their risk alleles. Specifically, the interaction between rs2596542 and rs2069705 polymorphisms increased the HCC risk by 1.41 times and between rs2596542 and rs2069727 polymorphisms the increased risk of HCC by 5.56 times. CONCLUSIONS IFN gamma rs2069727 and MICA rs2596542 polymorphisms may be related to the incidence of HCC. Interaction exists between the polymorphisms of IFN-gamma and MICA, which may increase risk of HCC. PMID- 26893441 TI - Subtle presentation of active primary biliary cirrhosis in chronic hepatitis B: a case report. AB - We are describing an interesting case of two chronic liver diseases in a 48-year old Chinese woman. While chronic hepatitis B is a common entity in Asia, the patient was later found to have active, asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy. This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition. Clinical vigilance, especially in atypical clinical presentations, can result in early accurate diagnosis and prompt treatment. PMID- 26893442 TI - The effect of disc-shaped gastric resection of anastomosis site on reducing postoperative dysphagia and stricture after esophagogastric anastomosis in patients with esophageal cancer. AB - BACKGROUND: Esophagectomy remains the most reliable technique for managing esophageal cancer, but anastomotic complications including postoperative leak, ischemia and stricture negatively affect outcomes of this specific surgery. The aim of this study was to evaluate the effects of a novel method of esophagogastric anastomosis for reducing postoperative dysphagia and stricture formation. METHODS: Eighty patients who were scheduled for esophagectomy due to esophageal cancer were randomly assigned into two groups: intervention and control (40 each). In the control group, the esophagogastric anastomosis was performed with a linear gastric incision, whilst in the intervention group a new method of disc-shaped gastric resection for anastomosis was applied. Postoperative outcomes were compared between the two groups. RESULTS: The incidence of postoperative dysphagia and anastomotic stricture was significantly lower in the disc-shaped resection group (dysphagia 45% vs 75%, P = 0.02; stricture 12.5% vs 32.5%, P = 0.03), whilst the length of stay in an intensive care unit (ICU), anastomotic leakage and other complications were not significantly different between the two groups (all P > 0.05). CONCLUSION: Anastomotic complications can be reduced by improving surgical techniques. The decreased incidence of postoperative dysphagia and anastomotic stricture in our study may be partly due to providing the proper diameter for the site of anastomosis when using the disc-shaped gastric resection method. Hence, this new method can improve the clinical outcomes of patients who undergo esophagectomy with esophagogastric anastomosis. PMID- 26893443 TI - Intraoperative Hydroxyethyl Starch and its Effects on Different Fibrinogen Measurements. AB - BACKGROUND: Intravenous fluids with synthetic colloids such as hydroxyethyl starch (HES) are known to interfere with plasma fibrinogen concentration measurements. The aim of this study was to evaluate the effects of an HES solution on fibrinogen measurements in a clinical setting. METHODS: The study was performed in patients who received at least 1 L of HES during intracranial tumor resection surgery. Blood samples were drawn before the start of surgery (baseline), after infusion of 1 L of HES, and at later time points. The fibrinogen concentration was measured using 3 different methods: (a) enzyme linked immunosorbent assay (ELISA), (b) Clauss method with a photometric readout, and (c) Clauss method with an electromechanical readout. In addition, the fibrin based clot quality was evaluated with the thromboelastometric FIBTEM test. RESULTS: Forty patients were enrolled, and 25 patients were included in the analysis. The fibrinogen concentrations at baseline were 2.2, 2.3, and 2.6 g/L and after 1 L of HES 1.6, 1.7, and 1.9 g/L as measured by ELISA, the photometric test, and the electromechanical test, respectively. The electromechanical Clauss test measured significantly higher concentrations at these time points. The relative decrease, however, was comparable between methods (31%, 29%, and 25%, respectively) but significantly lower than the 44% relative decrease with FIBTEM maximum clot firmness. CONCLUSION: Despite providing different fibrinogen concentration values at baseline, the relative decrease in fibrinogen concentration after HES infusion was comparable among the 3 tests. In contrast, fibrin-based clot quality was more affected than fibrinogen concentration tests by HES infusion. PMID- 26893444 TI - Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease. AB - The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins. PMID- 26893446 TI - Five minutes with . . . John Appleby. PMID- 26893445 TI - Evidence-Based Development and Rationale for Once-Daily Rivaroxaban Dosing Regimens Across Multiple Indications. AB - BACKGROUND: Rivaroxaban, a direct factor Xa inhibitor, has been developed to meet clinical needs in a broad range of indications in adults: prevention of venous thromboembolism after elective hip or knee replacement surgery, treatment and secondary prevention of venous thromboembolism, prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation having one or more risk factors, and in Europe, prevention of atherothrombotic events after an acute coronary syndrome in patients with elevated cardiac biomarkers. However, the precise dose and regimen vary with the indication, leading to this effort to provide clarity concerning the appropriate use of rivaroxaban. This article reviews the clinical development program for rivaroxaban and summarizes the evidence for each approved, indication-specific dose regimen. RESULTS: Although initially investigated for twice-daily dosing, early observations, including the finding that the pharmacodynamic effects of rivaroxaban last longer than the elimination half-life, suggested that once-daily dosing might be attainable and effective. These observations were evaluated within the extensive phase II program, which, together with pharmacology studies, provides the evidence underpinning the selection of once-daily regimens for most, but not all, of the approved clinical indications for rivaroxaban. CONCLUSION: The evidence for each dosing regimen demonstrates that although pharmacology studies are of paramount importance, dose regimens must be subjected to careful empirical validation. Once daily dosing was shown to be clinically appropriate for most rivaroxaban indications. Furthermore, a "one size fits all" approach to dosing frequency is unlikely to result in a regimen that yields optimal patient outcomes across different indications. PMID- 26893447 TI - Intensive Care Nurses' Views and Practices for Eye Care: An International Comparison. AB - Eye care is an important area of critical care. However, lack of eye care studies is a common issue across the globe. The aim of this study is to determine the views and practices of intensive care unit (ICU) nurses on eye care in Turkey and Palestine. This descriptive study was conducted using a self-administrated questionnaire. The data were collected from 111 nurses in nine kinds of ICUs in two education hospital. Normal saline (75.9%) was the most commonly reported solution for eye hygiene among the Palestinian nurses, and gauze soaked in normal saline or sterile water (64.3%) were the most frequently used supplies by the Turkish nurses. Although both Palestinian and Turkish ICU nurses took some precautions to prevent eye complications in critical patients, there were some gaps and insufficiencies in the eye care of ICU patients. There is a need for continuing training in this area. PMID- 26893448 TI - Complete Atrioventricular Block as a Complication of Varicella Infection in a Child: Recovery With a Single Dose of Intravenous Immunoglobulin Therapy. PMID- 26893454 TI - Comprehensive Phylogenetic Analysis Sheds Light on the Diversity and Origin of the MLO Family of Integral Membrane Proteins. AB - Mildew resistanceLocusO(MLO) proteins are polytopic integral membrane proteins that have long been considered as plant-specific and being primarily involved in plant-powdery mildew interactions. However, research in the past decade has revealed that MLO proteins diverged into a family with several clades whose members are associated with different physiological processes. We provide a largely increased dataset of MLO amino acid sequences, comprising nearly all major land plant lineages. Based on this comprehensive dataset, we defined seven phylogenetic clades and reconstructed the likely evolution of the MLO family in embryophytes. We further identified several MLO peptide motifs that are either conserved in all MLO proteins or confined to one or several clades, supporting the notion that clade-specific diversification of MLO functions is associated with particular sequence motifs. In baker's yeast, some of these motifs are functionally linked to transmembrane (TM) transport of organic molecules and ions. In addition, we attempted to define the evolutionary origin of the MLO family and found that MLO-like proteins with highly diverse membrane topologies are present in green algae, but also in the distinctly related red algae (Rhodophyta), Amoebozoa, and Chromalveolata. Finally, we discovered several instances of putative fusion events between MLO proteins and different kinds of proteins. Such Rosetta stone-type hybrid proteins might be instructive for future analysis of potential MLO functions. Our findings suggest that MLO is an ancient protein that possibly evolved in unicellular photosynthetic eukaryotes, and consolidated in land plants with a conserved topology, comprising seven TM domains and an intrinsically unstructured C-terminus. PMID- 26893455 TI - Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria. AB - Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including thecus(copper sensing copper efflux system), andpco(plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative ofEnterobacter cloacaeas the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the originalpcomodule was replaced by a divergentpcohomolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens. PMID- 26893456 TI - Coevolution between Nuclear-Encoded DNA Replication, Recombination, and Repair Genes and Plastid Genome Complexity. AB - Disruption of DNA replication, recombination, and repair (DNA-RRR) systems has been hypothesized to cause highly elevated nucleotide substitution rates and genome rearrangements in the plastids of angiosperms, but this theory remains untested. To investigate nuclear-plastid genome (plastome) coevolution in Geraniaceae, four different measures of plastome complexity (rearrangements, repeats, nucleotide insertions/deletions, and substitution rates) were evaluated along with substitution rates of 12 nuclear-encoded, plastid-targeted DNA-RRR genes from 27 Geraniales species. Significant correlations were detected for nonsynonymous (dN) but not synonymous (dS) substitution rates for three DNA-RRR genes (uvrB/C, why1, and gyrA) supporting a role for these genes in accelerated plastid genome evolution in Geraniaceae. Furthermore, correlation between dN of uvrB/C and plastome complexity suggests the presence of nucleotide excision repair system in plastids. Significant correlations were also detected between plastome complexity and 13 of the 90 nuclear-encoded organelle-targeted genes investigated. Comparisons revealed significant acceleration of dN in plastid targeted genes of Geraniales relative to Brassicales suggesting this correlation may be an artifact of elevated rates in this gene set in Geraniaceae. Correlation between dN of plastid-targeted DNA-RRR genes and plastome complexity supports the hypothesis that the aberrant patterns in angiosperm plastome evolution could be caused by dysfunction in DNA-RRR systems. PMID- 26893457 TI - Bilateral robotic priming before task-oriented approach in subacute stroke rehabilitation: a pilot randomized controlled trial. AB - OBJECTIVES: To investigate the treatment effects of bilateral robotic priming combined with the task-oriented approach on motor impairment, disability, daily function, and quality of life in patients with subacute stroke. DESIGN: A randomized controlled trial. SETTING: Occupational therapy clinics in medical centers. SUBJECTS: Thirty-one subacute stroke patients were recruited. INTERVENTIONS: Participants were randomly assigned to receive bilateral priming combined with the task-oriented approach (i.e., primed group) or to the task oriented approach alone (i.e., unprimed group) for 90 minutes/day, 5 days/week for 4 weeks. The primed group began with the bilateral priming technique by using a bimanual robot-aided device. MAIN MEASURES: Motor impairments were assessed by the Fugal-Meyer Assessment, grip strength, and the Box and Block Test. Disability and daily function were measured by the modified Rankin Scale, the Functional Independence Measure, and actigraphy. Quality of life was examined by the Stroke Impact Scale. RESULTS: The primed and unprimed groups improved significantly on most outcomes over time. The primed group demonstrated significantly better improvement on the Stroke Impact Scale strength subscale ( p = 0.012) and a trend for greater improvement on the modified Rankin Scale ( p = 0.065) than the unprimed group. CONCLUSION: Bilateral priming combined with the task-oriented approach elicited more improvements in self-reported strength and disability degrees than the task-oriented approach by itself. Further large-scale research with at least 31 participants in each intervention group is suggested to confirm the study findings. PMID- 26893458 TI - Patient participation groups in general practice: what are they for, where are they going? PMID- 26893461 TI - Chronic Pelvic Pain Caused by Laxity of the Uterosacral Ligaments: Are the Posterior Fornix Syndrome and the Allen-Masters Syndrome Synonyms? PMID- 26893462 TI - Abdominal Aortic Aneurysm as a Long Time Cause of Low Back Pain and Vertebral Scalloping. PMID- 26893460 TI - Introgression maintains the genetic integrity of the mating-type determining chromosome of the fungus Neurospora tetrasperma. AB - Genome evolution is driven by a complex interplay of factors, including selection, recombination, and introgression. The regions determining sexual identity are particularly dynamic parts of eukaryotic genomes that are prone to molecular degeneration associated with suppressed recombination. In the fungus Neurospora tetrasperma, it has been proposed that this molecular degeneration is counteracted by the introgression of nondegenerated DNA from closely related species. In this study, we used comparative and population genomic analyses of 92 genomes from eight phylogenetically and reproductively isolated lineages of N. tetrasperma, and its three closest relatives, to investigate the factors shaping the evolutionary history of the genomes.We found that suppressed recombination extends across at least 6 Mbp (~ 63%) of the mating-type (mat) chromosome in N. tetrasperma and is associated with decreased genetic diversity, which is likely the result primarily of selection at linked sites. Furthermore, analyses of molecular evolution revealed an increased mutational load in this region, relative to recombining regions. However, comparative genomic and phylogenetic analyses indicate that the mat chromosomes are temporarily regenerated via introgression from sister species; six of eight lineages show introgression into one of their mat chromosomes, with multiple Neurospora species acting as donors. The introgressed tracts have been fixed within lineages, suggesting that they confer an adaptive advantage in natural populations, and our analyses support the presence of selective sweeps in at least one lineage. Thus, these data strongly support the previously hypothesized role of introgression as a mechanism for the maintenance of mating-type determining chromosomal regions. PMID- 26893459 TI - Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network. AB - Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using multiple transient models and a CRISPR/Cas9-generated mutant, we show physiologically relevant phenotypes altering SHH signaling and eye development upon abrogation of ptch1 in zebrafish for which in vivo complementation assays using these models showed that all six patient missense mutations affect SHH signaling. Finally, through transcriptomic and ChIP analyses, we show that SOX2 binds to an intronic domain of the PTCH1 locus to regulate PTCH1 expression, findings that were validated both in vitro and in vivo. Together, these results demonstrate that PTCH1 mutations contribute to as much as 10% of ODA, identify the SHH signaling pathway as a novel effector of SOX2 activity during human ocular development, and indicate that ODA is likely the result of overactive SHH signaling in humans harboring mutations in either PTCH1 or SOX2. PMID- 26893463 TI - Epidural Glucocorticoid Injections for Spinal Stenosis, Interlaminal at the Worst Level. PMID- 26893464 TI - Reply to: Is It Not Important that We Ask the Right Question, the Right Way, on an Appropriate Sample of Patients? PMID- 26893465 TI - AAPM 2016 Annual Meeting Abstracts. PMID- 26893466 TI - AAPM 2016 Annual Meeting Late-Breaking Abstracts. PMID- 26893467 TI - Patient feedback for quality improvement in general practice. PMID- 26893468 TI - WHO sets out $56m Zika virus response plan. PMID- 26893470 TI - Multiple Metazoan Life-span Interventions Exhibit a Sex-specific Strehler-Mildvan Inverse Relationship Between Initial Mortality Rate and Age-dependent Mortality Rate Acceleration. AB - The Gompertz equation describes survival in terms of initial mortality rate (parameter a), indicative of health, and age-dependent acceleration in mortality rate (parameter b), indicative of aging. Gompertz parameters were analyzed for several published studies. In Drosophila females, mating increases egg production and decreases median life span, consistent with a trade-off between reproduction and longevity. Mating increased parameter a, causing decreased median life span, whereas time parameter b was decreased. The inverse correlation between parameters indicates the Strehler-Mildvan (S-M) relationship, where loss of low vitality individuals yields a cohort with slower age-dependent mortality acceleration. The steroid hormone antagonist mifepristone/RU486 reversed these effects. Mating and mifepristone showed robust S-M relationships across genotypes, and dietary restriction showed robust S-M relationship across diets. Because nutrient optima differed between females and males, the same manipulation caused opposite effects on mortality rates in females versus males across a range of nutrient concentrations. Similarly, p53 mutation in Drosophila and mTOR mutation in mice caused increased median life span associated with opposite direction changes in mortality rate parameters in females versus males. The data demonstrate that dietary and genetic interventions have sex-specific and sometimes sexually opposite effects on mortality rates consistent with sexual antagonistic pleiotropy. PMID- 26893469 TI - Gender Differences in the Combined Effects of Cardiovascular Disease and Osteoarthritis on Progression to Functional Impairment in Older Mexican Americans. AB - BACKGROUND: Comorbidity (COM) is an important issue in aging. Cardiovascular disease (CVD) and osteoarthritis separately and together may modify the trajectories of functional decline. This analysis examines whether specific and unrelated COMs influence functional change differently and vary by gender. METHODS: A cohort study of 1,789 (aged 60 years and older) Mexican Americans was followed annually for up to 10 years. We created four groups of COM (CVD alone, lower body osteoarthritis alone [OA], neither, or both). We employed mixed effects Poisson models with Instrumental Activities of Daily Living (IADL) as the outcome. We tested whether the association between COM and decline in functional status differed by gender. RESULTS: IADL impairments in those with CVD, OA, or both were significantly higher at baseline and increased more rapidly over time compared to those with neither condition. Compared to women with no COM, the number of IADL impairments in women with CVD alone were 1.36 times greater, with OA were 1.35 times greater, and both conditions were 1.26 times greater. Compared to men with no COM, IADL impairments in men with CVD alone were 1.15 times greater, OA alone were 1.12 times greater, and both were 1.26 times greater. CONCLUSIONS: Over time, the influence of COM on functional decline differs by specific combinations of COM and by gender. Aggregate COM scales obscure the biological and temporal heterogeneity in the effects of COM. Time-dependent specific COMs better assess the development of impairment. Women experience a higher burden of functional impairment due to COM than men. PMID- 26893471 TI - The Road to C4 Photosynthesis: Evolution of a Complex Trait via Intermediary States. AB - C4 photosynthesis enables high photosynthetic energy conversion efficiency as well as high nitrogen and water use efficiencies. Given the multitude of biochemical, structural and molecular changes in comparison with C3 photosynthesis, it appears unlikely that such a complex trait would evolve in a single step. C4 photosynthesis is therefore believed to have evolved from the ancestral C3 state via intermediary stages. Consequently, the identification and detailed characterization of plant species representing transitory states between C3 and C4 is important for the reconstruction of the sequence of evolutionary events, especially since C4 evolution occurred in very different phylogenetic backgrounds. There is also significant interest in engineering of C4 or at least C4-like elements into C3 crop plants. A detailed and mechanistic understanding of C3-C4 intermediates is likely to provide guidance for the experimental design of such approaches. Here we provide an overview on the most relevant results obtained on C3-C4 intermediates to date. Recent knowledge gains in this field will be described in more detail. We thereby concentrate especially on biochemical and physiological work. Finally, we will provide a perspective and outlook on the continued importance of research on C3-C4 intermediates. PMID- 26893472 TI - Promotion of Cyclic Electron Transport Around Photosystem I with the Development of C4 Photosynthesis. AB - C4 photosynthesis is present in approximately 7,500 species classified into 19 families, including monocots and eudicots. In the majority of documented cases, a two-celled CO2-concentrating system that uses a metabolic cycle of four-carbon compounds is employed. C4 photosynthesis repeatedly evolved from C3 photosynthesis, possibly driven by the survival advantages it bestows in the hot, often dry, and nutrient-poor soils of the tropics and subtropics. The development of the C4 metabolic cycle greatly increased the ATP demand in chloroplasts during the evolution of malic enzyme-type C4 photosynthesis, and the additional ATP required for C4 metabolism may be produced by the cyclic electron transport around PSI. Recent studies have revealed the nature of cyclic electron transport and the elevation of its components during C4 evolution. In this review, we discuss the energy requirements of C3 and C4 photosynthesis, the current model of cyclic electron transport around PSI and how cyclic electron transport is promoted during C4 evolution using studies on the genus Flaveria, which contains a number of closely related C3, C4 and C3-C4 intermediate species. PMID- 26893474 TI - The wrist that was not straight. PMID- 26893473 TI - Endurance training in early life results in long-term programming of heart mass in rats. AB - Being born small for gestational age increases the risk of developing adult cardiovascular and metabolic diseases. This study aimed to examine if early-life exercise could increase heart mass in the adult hearts from growth restricted rats. Bilateral uterine vessel ligation to induce uteroplacental insufficiency and fetal growth restriction in the offspring (Restricted) or sham surgery (Control) was performed on day 18 of gestation in WKY rats. A separate group of sham litters had litter size reduced to five pups at birth (Reduced litter), which restricted postnatal growth. Male offspring remained sedentary or underwent treadmill running from 5 to 9 weeks (early exercise) or 20 to 24 weeks of age (later exercise). Remarkably, in Control, Restricted, and Reduced litter groups, early exercise increased (P < 0.05) absolute and relative (to body mass) heart mass in adulthood. This was despite the animals being sedentary for ~4 months after exercise. Later exercise also increased adult absolute and relative heart mass (P < 0.05). Blood pressure was not significantly altered between groups or by early or later exercise. Phosphorylation of Akt Ser(473) in adulthood was increased in the early exercise groups but not the later exercise groups. Microarray gene analysis and validation by real-time PCR did not reveal any long term effects of early exercise on the expression of any individual genes. In summary, early exercise programs the heart for increased mass into adulthood, perhaps by an upregulation of protein synthesis based on greater phosphorylation of Akt Ser(473). PMID- 26893476 TI - Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes. AB - Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. (c)2016 AACR. PMID- 26893477 TI - Activation of the MDA-5-IPS-1 Viral Sensing Pathway Induces Cancer Cell Death and Type I IFN-Dependent Antitumor Immunity. AB - Melanoma differentiation-associated gene 5 (MDA-5, IFIH1), a cytosolic innate pattern recognition receptor, functions as a first line of defense against viral infection by sensing double-stranded RNA. Ectopic expression of MDA-5 has been shown to induce cancer cell death, but the mechanism of action by which MDA-5 exerts these cytotoxic effects is unclear. Here, we demonstrate that ectopic expression of MDA-5 via replication-incompetent adenovirus (Ad.Mda-5) initiates multiple signaling cascades, culminating in cytotoxicity and type I IFN production in mouse and human prostate cancer cells. This intrinsic dual activity of MDA-5 required the adaptor protein IFNbeta promoter stimulator 1 (IPS-1, MAVS) and could be functionally uncoupled. MDA-5 lacking N-terminal caspase recruitment domains (CARD) engaged an intracellular death program in cancer cells but was unable to efficiently stimulate the expression of IFNbeta. In contrast to cancer cells susceptible to MDA-5-mediated cytotoxicity, normal cells were highly resistant and instead developed a robust type I IFN response. Strikingly, intratumoral delivery of Ad.Mda-5 led to regression of preestablished prostate cancers and development of long-lasting antitumor immune memory, which was primarily attributed to the activation of tumor-reactive cytotoxic T lymphocytes and/or natural killer cells. Using the CARD-truncated MDA-5 mutant, silencing of IPS-1, and antibody blockade of the IFNalpha/beta receptor, we further demonstrate that type I IFN signaling was crucial for in situ MDA-5-induced protective antitumor immunity. Therefore, deliberately targeting the evolutionarily conserved MDA-5-IPS-1 antiviral pathway in tumors can provoke parallel tumoricidal and immunostimulatory effects that bridge innate and adaptive immune responses for the therapeutic treatment of cancer. Cancer Res; 76(8); 2166-76. (c)2016 AACR. PMID- 26893475 TI - Transcriptome Profiling of Tiller Buds Provides New Insights into PhyB Regulation of Tillering and Indeterminate Growth in Sorghum. AB - Phytochrome B (phyB) enables plants to modify shoot branching or tillering in response to varying light intensities and ratios of red and far-red light caused by shading and neighbor proximity. Tillering is inhibited in sorghum genotypes that lack phytochrome B (58M, phyB-1) until after floral initiation. The growth of tiller buds in the first leaf axil of wild-type (100M, PHYB) and phyB-1 sorghum genotypes is similar until 6 d after planting when buds of phyB-1 arrest growth, while wild-type buds continue growing and develop into tillers. Transcriptome analysis at this early stage of bud development identified numerous genes that were up to 50-fold differentially expressed in wild-type/phyB-1 buds. Up-regulation of terminal flower1, GA2oxidase, and TPPI could protect axillary meristems in phyB-1 from precocious floral induction and decrease bud sensitivity to sugar signals. After bud growth arrest in phyB-1, expression of dormancy associated genes such as DRM1, GT1, AF1, and CKX1 increased and ENOD93, ACCoxidase, ARR3/6/9, CGA1, and SHY2 decreased. Continued bud outgrowth in wild type was correlated with increased expression of genes encoding a SWEET transporter and cell wall invertases. The SWEET transporter may facilitate Suc unloading from the phloem to the apoplast where cell wall invertases generate monosaccharides for uptake and utilization to sustain bud outgrowth. Elevated expression of these genes was correlated with higher levels of cytokinin/sugar signaling in growing buds of wild-type plants. PMID- 26893478 TI - In Vivo Visualization and Characterization of Epithelial-Mesenchymal Transition in Breast Tumors. AB - The activation of the epithelial-to-mesenchymal transition (EMT) program is a critical step in cancer progression and metastasis, but visualization of this process at the single-cell level, especially in vivo, remains challenging. We established an in vivo approach to track the fate of tumor cells based on a novel EMT-driven fluorescent color switching breast cancer mouse model and intravital two-photon laser scanning microscopy. Specifically, the MMTV-PyMT, Rosa26-RFP GFP, and Fsp1-Cre triple transgenic mouse model was used to monitor the conversion of RFP-positive epithelial cells to GFP-positive mesenchymal cells in mammary tumors under the control of the Fsp1 (ATL1) promoter, a gate-keeper of EMT initiation. RFP-positive cells were isolated from the tumors, sorted, and transplanted into mammary fat pads of SCID mice to monitor EMT during breast tumor formation. We found that the conversion from RFP- to GFP-positive and spindle-shaped cells was a gradual process, and that GFP-positive cells preferentially localized close to blood vessels, independent of tumor size. Furthermore, cells undergoing EMT expressed high levels of the HGF receptor, c Met, and treatment of RFP-positive cells with the c-Met inhibitor, cabozantinib, suppressed the RFP-to-GFP conversion in vitro Moreover, administration of cabozantinib to mice with palpable RFP-positive tumors resulted in a silent EMT phenotype whereby GFP-positive cells exhibited reduced motility, leading to suppressed tumor growth. In conclusion, our imaging technique provides a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. Cancer Res; 76(8); 2094-104. (c)2016 AACR. PMID- 26893481 TI - Correction. PMID- 26893479 TI - Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport. AB - Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443-52. (c)2016 AACR. PMID- 26893483 TI - Aging Slows Access to Temporal Information From Working Memory. AB - Objectives: To evaluate the impact of aging on controlled memory search operations, we investigated the retrieval of temporal order information from working memory (WM). Method: Young and older adults completed a relative judgments-of-recency (JOR) task. In each trial, participants studied 5-item lists and were presented with two probes from the study list. Participants indicated the probe that had appeared more recently in the study list. Results: Analyses of accuracy data showed that young adults were more successful in correctly detecting the more recent probe compared with older adults. To evaluate the retrieval dynamics, we applied Hacker's (1980) serial scanning model on reaction time data. Results from the model fits revealed that older adults were slower in engaging in the serial memory search operations required to access temporal order information from WM. Discussion: These findings suggest that this age-related impairment in a JOR task might arise from a slower deployment of controlled memory operations, such as serial search. PMID- 26893480 TI - PR55alpha Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling. AB - The protein phosphatase 2 (PP2A) holoenzyme consists of a catalytic subunit, a scaffold subunit, and a regulatory subunit. Based on loss-of-function analysis using PP2A catalytic inhibitors or inhibition via tumor viral antigens, limited studies suggest that PP2A is a putative tumor suppressor. However, PP2A has also been shown to facilitate the activation of oncogenic signaling pathways when associated with specific regulatory subunits. In this study, we investigated the possible oncogenic role of PP2A in pancreatic cancer. We found a striking increase in the expression of PR55alpha (PPP2R2A), a PP2A regulatory subunit, in pancreatic cancer cells compared with normal pancreatic epithelial cells. Consistently, PR55alpha expression was markedly elevated in pancreatic ductal adenocarcinoma tissues compared with adjacent normal pancreatic tissues (P < 0.0001) and correlated with poor survival of pancreatic cancer patients (P < 0.0003). RNAi-mediated depletion of PR55alpha in pancreatic cancer cell lines resulted in diminished phosphorylation of both AKT and ERK1/2 (MAPK3/1) and decreased protein levels of beta-catenin (CTNNB1). Accordingly, pancreatic cancer cells with reduced PR55alpha expression exhibited significantly impaired properties of transformation, including attenuated cell growth, clonogenicity, mobility, and anchorage-independent growth. Moreover, orthotopic implantation of PR55alpha-depleted pancreatic cancer cells into nude mice resulted in markedly reduced tumorigenicity (P < 0.001) and distant metastases. Together, these results suggest that PR55alpha promotes pancreatic cancer development by sustaining hyperactivity of multiple oncogenic signaling pathways, including AKT, ERK, and Wnt. These studies also provide a basis for exploring PR55alpha as a diagnostic or therapeutic target in pancreatic cancer. Cancer Res; 76(8); 2243 53. (c)2016 AACR. PMID- 26893484 TI - In the balance: evolving trends in the satisfaction of junior doctors inside and outside work. PMID- 26893485 TI - miR-223 contributes to the AGE-promoted apoptosis via down-regulating insulin like growth factor 1 receptor in osteoblasts. AB - Advanced glycation end products (AGEs) have been confirmed to induce bone quality deterioration in diabetes mellitus (DM), and to associate with abnormal expression of miRNAs in DM patients or in vitro Recently, miRNAs have been recognized to mediate the onset or progression of DM. In the present study, we investigated the regulation on miR-223 level by AGE-BSA treatment in osteoblast like MC3T3-E1 cells, with real-time quantitative PCR assay. And then we examined the inhibition of insulin-like growth factor 1 receptor (IGF-1R) expression by miR-223, via targeting of the 3' UTR of IGF-1R with real-time quantitative PCR, western blotting and luciferase reporter assay. Then we explored the regulation of miR-223 and IGF-1R levels, via the lentivirus-mediated miR-223 inhibition and IGF-1R overexpression in the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It was demonstrated that AGE-BSA treatment with more than 100 MUg/ml significantly up regulated miR-223 level, whereas down-regulated IGF-1R level in MC3T3-E1 cells. And the up-regulated miR-223 down-regulated IGF-1R expression in both mRNA and protein levels, via targeting the 3' UTR of IGF-1R Moreover, though the AGE-BSA treatment promoted apoptosis in MC3T3-E1 cells, the IGF-1R overexpression or the miR-223 inhibition significantly attenuated the AGE-BSA-promoted apoptosis in MC3T3-E1 cells. In summary, our study recognized the promotion of miR-223 level by AGE-BSA treatment in osteoblast-like MC3T3-E1 cells. The promoted miR-223 targeted IGF-1R and mediated the AGE-BSA-induced apoptosis in MC3T3-E1 cells. It implies that miR-223 might be an effective therapeutic target to antagonize the AGE-induced damage to osteoblasts in DM. PMID- 26893487 TI - Response to: 'Evaluation of the association between anticarbamylated protein antibodies and longitudinal course of functional ability in rheumatoid arthritis' by Ajeganova et al. PMID- 26893486 TI - Allopurinol dose relative to renal function and risk of hypersensitivity reactions. PMID- 26893488 TI - Effects of colchicine on risk of cardiovascular events among patients with gout: as evidence accrues, is it time for a randomised trial? PMID- 26893490 TI - Engaging Older Adults in Environmental Volunteerism: The Retirees in Service to the Environment Program. AB - Purpose of the Study: Retirees in Service to the Environment (RISE) is a program designed to promote participation of older people in volunteering for the environment. Based on principles of adult learning and best practices for the development of effective volunteer programs, RISE engaged older individuals in environmental volunteering and involved them in community stewardship activities. Design and Methods: This article details the development and formative evaluation of RISE. We describe program assessment, benefits to the community, and effects on participants. Results: The program successfully recruited individuals new to environmental volunteering and substantial hours of volunteer time were provided to communities. Program satisfaction was high and preliminary evidence suggests positive outcomes from RISE participation. Implications: The innovative structure combined with local relevance of the RISE program has the potential to expand older adults' engagement in environmental volunteerism. PMID- 26893489 TI - Middle-Aged Offspring's Support to Aging Parents With Emerging Disability. AB - Purpose of the Study: A vast literature has examined family caregivers, but few studies explore transitions from providing ordinary support to parents to situations involving increasing dependency. Using 2 waves of data, we examined how parents' increasing disability in activities of daily living (ADL) is associated with changes in everyday support patterns, relationship quality, and psychological well-being of middle-aged offspring, taking into account other informal and paid help to the parent. Design and Methods: Three hundred and eighty middle-aged adults reported on everyday support they provided to each parent (N = 487) and parent's ADL at baseline and 5 years later. Results: Increased parents' disability led to increases in offspring's support, in particular tangible support. Support given by offspring was lower when parents received paid help but was not affected by help from other informal members (e.g., family members, friends). Increased disability was associated with decreases in positive relationship quality with parents; as well, offspring who provided actual help with ADL reported increases in negative relationship quality. Implications: The effects of increasing parents' disability on relationship quality and involvement of other informal and paid help may have implications for the longer-term impact of care on both offspring and their parents. PMID- 26893491 TI - Evaluation of Subscription-based Culture Change Models in Care Settings: Findings From a Systematic Review. AB - PURPOSE OF THE STUDY: Person-centered culture change models to which aged care service providers subscribe are gaining increasing traction. It has been suggested that culture change initiatives broadly are subject to a range of issues. It is difficult, however, to draw out from the existing literature specific information about the scope and quality of evidence regarding subscription-based approaches. The purpose of this study was to identify and review the peer-reviewed literature regarding these subscription-based models. DESIGN AND METHODS: The review used the Joanna Briggs Institute process and tools. Studies reporting on subscription-based person-centered culture change models in health and aged care, published in peer-reviewed literature in English up to and including 2015 were identified and assessed. In all, 28 articles reporting on 33 studies were included in the review. RESULTS: There was no single model for which a significant body of evidence was identified, and approaches to outcomes were fragmented. Research approaches varied. Rigor and reporting were of concern; however, strengths of the evidence base included generally adequate sample sizes and the use of multiple methods including large data sets and standardized scales. IMPLICATIONS: Despite their structured approaches, research and evaluation for subscription-based models are limited, ad hoc, and fragmented. A more comprehensive program of research that is embedded in the implementation process is needed. Recommendations include use of longitudinal study designs, attention to implementation and contextual factors, and measurement of both process and outcomes across the full range of culture change domains. PMID- 26893492 TI - Increased Nicotiana tabacum fitness through positive regulation of carotenoid, gibberellin and chlorophyll pathways promoted by Daucus carota lycopene beta cyclase (Dclcyb1) expression. AB - Carotenoids, chlorophylls and gibberellins are derived from the common precursor geranylgeranyl diphosphate (GGPP). One of the enzymes in carotenoid biosynthesis is lycopene beta-cyclase (LCYB) that catalyzes the conversion of lycopene into beta-carotene. In carrot, Dclcyb1 is essential for carotenoid synthesis in the whole plant. Here we show that when expressed in tobacco, increments in total carotenoids, beta-carotene and chlorophyll levels occur. Furthermore, photosynthetic efficiency is enhanced in transgenic lines. Interestingly, and contrary to previous observations where overexpression of a carotenogenic gene resulted in the inhibition of the synthesis of gibberellins, we found raised levels of active GA4 and the concommitant increases in plant height, leaf size and whole plant biomass, as well as an early flowering phenotype. Moreover, a significant increase in the expression of the key carotenogenic genes, Ntpsy1, Ntpsy2 and Ntlcyb, as well as those involved in the synthesis of chlorophyll (Ntchl), gibberellin (Ntga20ox, Ntcps and Ntks) and isoprenoid precursors (Ntdxs2 and Ntggpps) was observed. These results indicate that the expression of Dclcyb1 induces a positive feedback affecting the expression of isoprenoid gene precursors and genes involved in carotenoid, gibberellin and chlorophyll pathways leading to an enhancement in fitness measured as biomass, photosynthetic efficiency and carotenoid/chlorophyll composition. PMID- 26893493 TI - Dissecting stimulus-specific Ca2+ signals in amyloplasts and chloroplasts of Arabidopsis thaliana cell suspension cultures. AB - Calcium is used by plants as an intracellular messenger in the detection of and response to a plethora of environmental stimuli and contributes to a fine-tuned internal regulation. Interest in the role of different subcellular compartments in Ca(2+) homeostasis and signalling has been growing in recent years. This work has evaluated the potential participation of non-green plastids and chloroplasts in the plant Ca(2+) signalling network using heterotrophic and autotrophic cell suspension cultures from Arabidopsis thaliana plant lines stably expressing the bioluminescent Ca(2+) reporter aequorin targeted to the plastid stroma. Our results indicate that both amyloplasts and chloroplasts are involved in transient Ca(2+) increases in the plastid stroma induced by several environmental stimuli, suggesting that these two functional types of plastids are endowed with similar mechanisms for handling Ca(2+) A comparison of the Ca(2+) trace kinetics recorded in parallel in the plastid stroma, the surface of the outer membrane of the plastid envelope, and the cytosol indicated that plastids play an essential role in switching off different cytosolic Ca(2+) signals. Interestingly, a transient stromal Ca(2+) signal in response to the light-to-dark transition was observed in chloroplasts, but not amyloplasts. Moreover, significant differences in the amplitude of specific plastidial Ca(2+) changes emerged when the photosynthetic metabolism of chloroplasts was reactivated by light. In summary, our work highlights differences between non-green plastids and chloroplasts in terms of Ca(2+) dynamics in response to environmental stimuli. PMID- 26893494 TI - STP10 encodes a high-affinity monosaccharide transporter and is induced under low glucose conditions in pollen tubes of Arabidopsis. AB - Pollen tubes are fast growing, photosynthetically inactive cells. Their energy demand is covered by specific transport proteins in the plasma membrane that mediate the uptake of sugars. Here we report on the functional characterization of AtSTP10, a previously uncharacterized member of the SUGAR TRANSPORT PROTEIN family. Heterologous expression of STP10 cDNA in yeast revealed that the encoded protein catalyses the high-affinity uptake of glucose, galactose and mannose. The transporter is sensitive to uncouplers of transmembrane proton gradients, indicating that the protein acts as a hexose-H(+)symporter. Analyses of STP10 mRNA and STP10 promoter-reporter gene studies revealed a sink-specific expression pattern of STP10 in primordia of lateral roots and in pollen tubes. This restriction to sink organs is mediated by intragenic regions of STP10 qPCR analyses with cDNA of in vitro grown pollen tubes showed that STP10 expression was down-regulated in the presence of 50mM glucose. However, in pollen tubes of glucose-insensitive plants, which lack the glucose sensor hexokinase1 (HXK1), no glucose-induced down-regulation of STP10 expression was detected. A stp10T-DNA insertion line developed normally, which may point towards functional redundancy. The data presented in this paper indicate that a high-affinity glucose uptake system is induced in growing pollen tubes under low glucose conditions and that this regulation may occur through the hexokinase pathway. PMID- 26893495 TI - Implantable cardioverter defibrillator therapy in young individuals: comparison of conventional and subcostal approaches-a single-centre experience. AB - AIM: The aim of our study is to compare two approaches of implantable cardiac defibrillator (ICD) implantation, conventional (supra/subpectoral) and subcostal in young adults in terms of procedural complications and adverse events encountered during follow-up. METHODS AND RESULTS: From January 2007 to December 2013, all patients under the age of 50 years who received an ICD in our centre were included in this study. Patient's hospital records were analysed for procedural complications and adverse events during follow-up until December 2014. Data from device on first interrogation after implantation and on follow-up were also noted. A total of 106 patients of which 40.6% had Brugada's syndrome (65.1% male, age 33.6 +/- 10.97 years) were included in analysis; 71 (61%) had ICD placed in (sub/supra) pectoral and 35 (33%) in subcostal position. Only seven patients received an epicardial lead system. During the follow-up period of 2.1 +/- 1.8 years, 84.90% of the patients had no adverse events. Most of the complications, procedural and during follow-up, occur in conventionally placed, pectoral ICD. Lead follow-up data in both groups, conventional and subcostal, showed no difference in right ventricular (RV) shock impedance and R wave sensing, P-value = 0.56 and 0.77, respectively. Lead survival was 95 and 97%, respectively, in conventional and subcostal groups over a mean follow-up of 2.1 +/- 1.8 years. Log-rank test for lead survival was not significant in terms of site of implantation. CONCLUSION: To the best our knowledge, this is the first study demonstrating subcostal ICD placement in young adults and resulting in equivalent to better outcomes when compared with conventionally placed pectoral ICD. Subcostal ICD placement might be considered an alternative option in young adults as it results in better procedural outcomes and also comparable rate of adverse events during follow-up, but bigger studies with a larger number of patients are needed for a definitive conclusion. PMID- 26893496 TI - Performance of handheld electrocardiogram devices to detect atrial fibrillation in a cardiology and geriatric ward setting. AB - AIMS: To determine the usability, accuracy, and cost-effectiveness of two handheld single-lead electrocardiogram (ECG) devices for atrial fibrillation (AF) screening in a hospital population with an increased risk for AF. METHODS AND RESULTS: Hospitalized patients (n = 445) at cardiological or geriatric wards were screened for AF by two handheld ECG devices (MyDiagnostick and AliveCor). The performance of the automated algorithm of each device was evaluated against a full 12-lead or 6-lead ECG recording. All ECGs and monitor tracings were also independently reviewed in a blinded fashion by two electrophysiologists. Time investments by nurses and physicians were tracked and used to estimate cost effectiveness of different screening strategies. Handheld recordings were not possible in 7 and 21.4% of cardiology and geriatric patients, respectively, because they were not able to hold the devices properly. Even after the exclusion of patients with an implanted device, sensitivity and specificity of the automated algorithms were suboptimal (Cardiology: 81.8 and 94.2%, respectively, for MyDiagnostick; 54.5 and 97.5%, respectively, for AliveCor; Geriatrics: 89.5 and 95.7%, respectively, for MyDiagnostick; 78.9 and 97.9%, respectively, for AliveCor). A scenario based on automated AliveCor evaluation in patients without AF history and without an implanted device proved to be the most cost-effective method, with a provider cost to identify one new AF patient of ?193 and ?82 at cardiology and geriatrics, respectively. The cost to detect one preventable stroke per year would be ?7535 and ?1916, respectively (based on average CHA2DS2 VASc of 3.9 +/- 2.0 and 5.0 +/- 1.5, respectively). Manual interpretation increases sensitivity, but decreases specificity, doubling the cost per detected patient, but remains cheaper than sole 12-lead ECG screening. CONCLUSION: Using AliveCor or MyDiagnostick handheld recorders requires a structured screening strategy to be effective and cost-effective in a hospital setting. It must exclude patients with implanted devices and known AF, and requires targeted additional 12-lead ECGs to optimize specificity. Under these circumstances, the expenses per diagnosed new AF patient and preventable stroke are reasonable. PMID- 26893497 TI - Flecainide-metoprolol combination reduces atrial fibrillation clinical recurrences and improves tolerability at 1-year follow-up in persistent symptomatic atrial fibrillation. AB - AIMS: Atrial fibrillation (AF) affects ~2% of the total population. In order to prevent AF recurrences, many anti-arrhythmic drugs are currently available, but most of them are burdened by serious side effects and suboptimal efficacy. The aim of the present study was to test efficacy and safety of a combination of flecainide and metoprolol in preventing AF clinical recurrences. METHODS AND RESULTS: This study is a monocentric, prospective, randomized, open-blinded trial on 173 patients with a recent episode of paroxysmal or persistent AF. Patients were randomized into group A (flecainide + metoprolol; n = 80), group B (flecainide only; n = 72), or group C (metoprolol only; n = 21). Main exclusion criteria were recent acute coronary syndrome, heart failure New York Heart Association class III-IV, left ventricular ejection fraction <0.40, atrioventricular conduction disorders, and severe bradycardia. Primary endpoint was symptomatic recurrence over 1-year follow-up. Secondary endpoint was quality of life (QoL) over 1-year follow-up, as assessed by the SF-36 and Atrial Fibrillation Severity Scale questionnaires. Combination therapy with flecainide and metoprolol significantly reduced recurrences at 1-year follow-up when compared with flecainide alone in the whole population (66.7 vs. 46.8%; P < 0.001) and in patients with persistent AF (71.1 vs. 43.6%; P = 0.025) while adding beta-blocker therapy to paroxysmal AF showed no benefit over IC anti arrhythmic drug-only. Patients randomized to combination therapy experienced a significant improvement of QoL when compared with those assigned to a flecainide only regimen irrespective of AF type. CONCLUSION: Flecainide-metoprolol combination therapy improves effectiveness of rhythm control in persistent symptomatic AF and increases tolerability, with a concomitant reduction of side effects and a better compliance. PMID- 26893499 TI - Comment on 'Inserting the etonogestrel contraceptive implant'. PMID- 26893501 TI - One small SNP for receptor virus entry, one giant leap for hepatitis B? PMID- 26893502 TI - The utility of salutogenesis for guiding health promotion: the case for young people's well-being. AB - Twenty years have passed since the publication of the seminal paper 'The salutogenic model as a theory to guide health promotion' (Health Promot Int 1996;11:11-18.), in which Antonovsky proposed salutogenesis and its central construct sense of coherence as a way of boosting the theoretical basis for health promotion activities. Since then there has been a notable amount of conceptual and empirical work carried out to further explore its significance. The aim of this paper is to critically assess the current theoretical status of salutogenesis and its utility to advance effective health promotion practice for young people. The assessment was carried out in the context of contemporary international policy agendas on well-being. An analytic framework was developed using the previous literature on the definition and function of theory. This organizing framework comprised four criteria: description, explanation, prediction and measurability. The paper concludes with a perspective on the status of salutogenesis as a theory and how it can be further developed. Specifically, the critical assessment highlighted that salutogenesis has been subjected to considerable empirical testing over the last few decades resulting in convincing evidence of the relevance and subsequent advancement of the idea. However, less emphasis seems to have been placed on a systematic process of testing and iteration to develop its theoretical basis. The paper identifies a number of aspects that should be developed to support the progression of salutogenesis to the next level. A research-practice cycle approach is proposed that can facilitate that important next step. PMID- 26893500 TI - The safety of vedolizumab for ulcerative colitis and Crohn's disease. AB - OBJECTIVE: Vedolizumab is a gut-selective antibody to alpha4beta7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). We report an integrated summary of the safety of vedolizumab. DESIGN: Safety data (May 2009 June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received >=1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. RESULTS: In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1-1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (<=0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor alpha antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p<0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p<0.0001). Investigator-defined infusion-related reactions were reported for <=5% of patients in each study. Eighteen vedolizumab-exposed patients (<1%) were diagnosed with a malignancy. CONCLUSIONS: Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. TRIAL REGISTRATION NUMBER: NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933. PMID- 26893503 TI - National Profile of Physical Therapists in Critical Care Units of Sri Lanka: Lower Middle-Income Country. AB - BACKGROUND: The availability and role of physical therapists in critical care is variable in resource-poor settings, including lower middle-income countries. OBJECTIVE: The aim of this study was to determine: (1) the availability of critical care physical therapist services, (2) the equipment and techniques used and needed, and (3) the training and continuous professional development of physical therapists. METHODS: All physical therapists working in critical care units (CCUs) of state hospitals in Sri Lanka were contacted. The study tool used was an interviewer-administered telephone questionnaire. RESULTS: The response rate was 100% (N=213). Sixty-one percent of the physical therapists were men. Ninety-four percent of the respondents were at least diploma holders in physical therapy, and 6% had non-physical therapy degrees. Most (n=145, 68%) had engaged in some continuous professional development in the past year. The majority (n=119, 56%) attended to patients after referral from medical staff. Seventy seven percent, 98%, and 96% worked at nights, on weekends, and on public holidays, respectively. Physical therapists commonly perform manual hyperinflation, breathing exercises, manual airway clearance techniques, limb exercises, mobilization, positioning, and postural drainage in the CCUs. Lack of specialist training, lack of adequate physical therapy staff numbers, a heavy workload, and perceived lack of infection control in CCUs were the main difficulties they identified. LIMITATIONS: Details on the proportions of time spent by the physical therapists in the CCUs, wards, or medical departments were not collected. CONCLUSIONS: The availability of physical therapist services in CCUs in Sri Lanka, a lower middle-income country, was comparable to that in high income countries, as per available literature, in terms of service availability and staffing, although the density of physical therapists remained very low, critical care training was limited, and resource limitations to physical therapy practices were evident. PMID- 26893505 TI - Therapists' Perceptions of Application and Implementation of AM-PAC "6-Clicks" Functional Measures in Acute Care: Qualitative Study. AB - BACKGROUND: Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" tools are functional measures used in acute care. No studies have identified reactions and perceptions of therapists in implementing these measures. OBJECTIVES: The purpose of this study was to explore therapists' perceptions regarding the application and implementation of AM-PAC "6-Clicks" tools. DESIGN: This study used a qualitative design with thematic analysis. METHODS: A convenience sample of 13 physical therapists and occupational therapists participated in semistructured telephone interviews. Interviews were recorded, transcribed, and coded, after which thematic analysis was used to determine common themes. RESULTS: Five themes were identified: (1) unclear purpose, (2) lack of confidence in scoring, (3) too simple for decision making or generalizing patient function, (4) no effect on clinical routine, and (5) potential for communicating patient function across disciplines. LIMITATIONS: Participants came from one health care system. A relatively small percentage of staff agreed to participate in this study, and additional interviews might have revealed new themes. CONCLUSIONS: As participants in this study implemented the AM-PAC "6-Clicks" tools, they considered the role of the measures, how they fit within the context of practice, and their value. They also were concerned with the accuracy and feasibility of the tools. The tools were accepted as potentially valuable to assist administrative decisions and research; however, they were not perceived as particularly useful for routine patient care. Participants lacked complete confidence in the reliability of their scoring and expressed concern that the scores might be substituted for their clinical decision making. They also felt that the tools were too simple to fully reflect patients' overall function and were not useful alone for discharge planning. Participants believed the tools had the potential to be used for communication among colleagues about patients' physical function. PMID- 26893506 TI - Obstacle Crossing During Gait in Children With Cerebral Palsy: Cross-Sectional Study With Kinematic Analysis of Dynamic Balance and Trunk Control. AB - BACKGROUND: Balance problems are common in children who have cerebral palsy (CP) but are active and ambulant. Control of the whole-body center of mass is critical in maintaining dynamic stability during challenging mobility tasks, such as clearing an obstacle while walking. OBJECTIVE: The objective of this study was to compare trunk and lower limb kinematics and center-of-mass control in children with CP and those in children with typical development during obstacle crossing. DESIGN: This was a cross-sectional study. Thirty-four children who were 5 to 17 years of age (17 with CP and 17 with typical development) and matched in age and height completed 2 gait trials involving crossing a 10-cm obstacle. METHODS: Three-dimensional kinematic and kinetic data were captured with a general-purpose 3-dimensional motion tracking system and forceplates. Trunk data were captured with a validated model. RESULTS: All children cleared the obstacle with similar hip and knee kinematics, step length, and single-support duration. In children with CP, step width was increased by 4.81 cm, and center-of-mass velocity was significantly slower at lead limb toe-off (0.31 m/s) and during lead limb clearance (0.2 m/s). Children with CP showed altered trunk and pelvis movement, characterized by significantly greater pelvic obliquity, pelvic tilt, and trunk rotation throughout the task, increased lateral trunk lean during lead limb crossing (3.7 degrees ), and greater sagittal trunk movement as the trail limb crossed (5.1 degrees ). LIMITATIONS: The study was not powered to analyze differences between children with diplegia and those with hemiplegia. CONCLUSIONS: Children with CP required greater adjustments at the trunk and pelvis to achieve successful obstacle crossing. The increase in trunk movement could have been compensatory for reduced stability distally or for a primary problem reflecting poor proximal control. The findings suggest that rehabilitation should focus on both proximal trunk control and distal stability to improve balance. PMID- 26893507 TI - Effects of Pilates-Based Core Stability Training in Ambulant People With Multiple Sclerosis: Multicenter, Assessor-Blinded, Randomized Controlled Trial. AB - BACKGROUND: Pilates exercise is often undertaken by people with multiple sclerosis (MS) who have balance and mobility difficulties. OBJECTIVES: The primary aim of the study was to compare the effects of 12 weeks of Pilates exercises with relaxation on balance and mobility. Secondary aims were: (1) to compare standardized exercises with relaxation and (2) to compare Pilates exercises with standardized exercises. METHODS: A multicenter, assessor-blinded, randomized controlled trial was conducted. Participants with Expanded Disability Status Scale scores of 4.0 to 6.5 were randomly allocated to groups receiving 12 weeks of Pilates exercises, standardized exercises, or relaxation. Assessments were undertaken at baseline and weeks 12 and 16 (primary outcome measure: 10 Meter Timed Walk Test [10MTW]). RESULTS: One hundred participants (mean age=54 years, 74% female) were randomized to study groups. Six participants relapsed (withdrew from the study), leaving 94 participants for intention-to-treat analysis. There was no significant difference in mean 10MTW measurements between the Pilates and relaxation groups. At 12 weeks, there was a mean reduction of 4.2 seconds for the standardized exercise group compared with the relaxation group (95% confidence interval [relaxation group minus standardized exercise group measurements]=0.0, 8.4) and a mean reduction of 3.7 seconds for the Pilates group compared with the standardized exercise group (95% confidence interval [Pilates group minus standardized exercise group measurements]=-0.4 to 7.8). At 16 weeks, mean 10MTW times for the standardized exercise group remained quicker than those for the Pilates and relaxation groups, although the differences were nonsignificant. There were no significant differences between the Pilates and relaxation groups for any secondary outcome measure. LIMITATIONS: In this study, therapists were limited to a standardized basket of exercises that may have affected the study outcomes. Furthermore, choosing measures such as posturography to assess balance, accelerometry to assess walking, or a specific trunk assessment scale might have been more responsive in detecting changes in outcome. CONCLUSION: Participants did not improve significantly, either in the short term or at the 4-week follow-up, on the 10MTW after 12 weeks of Pilates exercises compared with 12 weeks of relaxation. PMID- 26893504 TI - NF-kappaB Signaling Pathway in Controlling Intervertebral Disk Cell Response to Inflammatory and Mechanical Stressors. AB - BACKGROUND: Intervertebral disk degeneration (IDD) has a greater than 90% lifetime incidence and is one of the leading causes of chronic back pain in the United States. Despite the high societal cost of IDD, there is limited understanding of the biological effects of mechanical overloading on further degeneration. The transcription factor NF-kappaB (nuclear factor kappaB) has been implicated as a key mediator of disk cell response to inflammatory and mechanical stresses and represents a potential control point. OBJECTIVE: The study objective was to measure the effect of NF-kappaB signaling pathway inhibition on annulus fibrosus (AF) cell matrix synthesis and gene expression under conditions of combined inflammatory and mechanical stimulation. METHODS: Annulus fibrosus cells were harvested from rabbit intervertebral disks and grown in vitro on flexible plates. The cells were exposed to inflammatory and mechanical stimulation for 24 hours with and without NF-kappaB inhibition. Nuclear translocation of NF-kappaB was measured via immunofluorescent staining. Intervertebral disk cell homeostasis was assessed via inflammatory, anabolic, and catabolic gene expression and via matrix synthetic ability. RESULTS: NF-kappaB nuclear translocation in response to interleukin-1 beta (IL-1beta) was reversed with exposure to NF-kappaB inhibition. NF-kappaB inhibition decreased matrix metalloproteinase-3, inducible nitric oxide synthase, and cyclooxygenase-2 gene expression and prostaglandin E2 production response to combined inflammatory and mechanical stimulation. Proteoglycan and collagen synthesis were decreased by combined stimulation, but this effect was not reversed by NF-kappaB inhibition. LIMITATIONS: In vitro modeling of conditions within the disk may not fully reflect the response that AF cells have in native matrix. CONCLUSIONS: NF-kappaB signaling mediates catabolic and inflammatory responses to inflammatory and mechanical stimulation but does not mediate the decrease in matrix synthesis under combined harmful stimulation. Identification of key control points in the cellular responses to inflammatory and mechanical stimuli will facilitate rational design of exercise-based therapies and facilitate synergistic treatments of novel biochemical treatments with rehabilitation regimens. PMID- 26893508 TI - Medial Longitudinal Arch Development of Children Aged 7 to 9 Years: Longitudinal Investigation. AB - BACKGROUND: It is unclear at what age the medial longitudinal arch (MLA) of the foot becomes stable in children. The influence of footwear on MLA development also is unknown. OBJECTIVE: The purpose of this study was to examine the MLA development of children using a longitudinal approach. The relationship between wearing different types of footwear and MLA development also was explored longitudinally. DESIGN: This was a longitudinal cohort observational study. METHODS: The MLA of 111 healthy children (mean age=6.9 years, SD=0.3) was evaluated using 3 parameters (arch index [AI], midfoot peak pressure [PP], and maximum force [MF]) extracted from dynamic foot loading measurements at baseline (t0), 10-month follow-up (t1), and 22-month follow-up (t2). Information on footwear usage was surveyed. Linear mixed modeling was used to test for differences in MLA over time. RESULTS: The MLA of the children remained stable over time (AI: t0/t1/t2=0.25 [95% confidence interval (CI)=0.24, 0.26]/0.25 [95% CI=0.24, 0.26]/0.25 [95% CI=0.24, 0.26]; P=.95). When the children's sex was considered, the AI of boys decreased (higher arch) with age (0.26 [95% CI=0.24, 0.27]/0.25 [95% CI=0.24, 0.27]/0.25 [95% CI=0.23, 0.27]; P=.02). Boys also displayed a flatter MLA than girls at age 6.9 years (AI: mean difference=0.02 [95% CI=0.01, 0.04]; P=.02). At baseline, children who wore closed-toe shoes displayed the lowest MLA overall (AI: closed-toe shoes/sandals/slippers=0.26 [95% CI=0.24, 0.28]/0.24 [95% CI=0.23, 0.25]/0.25 [95% CI=0.24, 0.26]; P<.01). Children who used slippers at toddlers' age experienced a higher PP (flatter arch) in later childhood than those who wore sandals (mean difference=31.60 kPa [95% CI=1.44, 61.75]; post hoc P=.04). LIMITATIONS: Information on the type of footwear worn was self-reported and, therefore, may be subjected to recall bias. CONCLUSIONS: The MLA of children remained stable from 7 to 9 years of age. The child's sex and the type of footwear worn during childhood may influence MLA development. PMID- 26893510 TI - Coordination and Symmetry Patterns During the Drop Vertical Jump in People With Chronic Ankle Instability and Lateral Ankle Sprain Copers. AB - BACKGROUND: The drop vertical jump (DVJ) task has previously been used to identify movement patterns associated with a number of injury types. However, no current research exists evaluating people with chronic ankle instability (CAI) compared with people coping with lateral ankle sprain (LAS) (referred to as "LAS copers") during this task. OBJECTIVE: The aim of this study was to identify the coping movement and motor control patterns of LAS copers in comparison with individuals with CAI during the DVJ task. DESIGN: This was a case-control study. METHODS: Seventy individuals were recruited at convenience within 2-weeks of sustaining a first-time acute LAS injury. One year following recruitment, these individuals were stratified into 2 groups: 28 with CAI and 42 LAS copers. They attended the testing laboratory to complete a DVJ task. Three-dimensional kinematic and sagittal-plane kinetic profiles were plotted for the lower extremity joints of both limbs for the drop jump phase (phase 1) and drop landing phase (phase 2) of the DVJ. The rate of impact modulation relative to body weight during both phases of the DVJ also was determined. RESULTS: Compared with LAS copers, participants with CAI displayed significant increases in hip flexion on their "involved" limb during phase 1 of the DVJ (23 degrees vs 18 degrees ) and bilaterally during phase 2 (15 degrees vs 10 degrees ). These movement patterns coincided with altered moment-of-force patterns at the hip on the "uninvolved" limb. LIMITATIONS: It is unknown whether these movement and motor control patterns preceded or occurred as a result of the initial LAS injury. CONCLUSIONS: Participants with CAI displayed hip-centered changes in movement and motor control patterns during a DVJ task compared with LAS copers. The findings of this study may give an indication of the coping mechanism underlying outcome following initial LAS injury. PMID- 26893509 TI - Dietary Protein Intake and Lean Muscle Mass in Survivors of Childhood Acute Lymphoblastic Leukemia: Report From the St. Jude Lifetime Cohort Study. AB - BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low lean muscle mass and muscle weakness, which may contribute to inactivity and early development of chronic diseases typically seen in older adults. Although increasing protein intake, in combination with resistance training, improves lean muscle mass in other populations, it is not known whether muscular tissue among survivors of ALL, whose impairments are treatment-related, will respond similarly. OBJECTIVE: The aim of this study was to evaluate associations among dietary protein intake, resistance training, and lean muscle mass in survivors of ALL and age-, sex-, and race-matched controls. DESIGN: This was a cross-sectional study. METHODS: Lean muscle mass was determined with dual-energy x-ray absorptiometry, dietary information with 24-hour recalls, and participation in resistance training with a questionnaire. Participants were 365 survivors of ALL (52% male; 87% white; median age=28.5 years, range=23.6-31.7) and 365 controls with no previous cancer. RESULTS: Compared with controls, survivors of ALL had lower lean muscle mass (55.0 versus 57.2 kg, respectively) and lower percentage of lean muscle mass (68.6% versus 71.4%, respectively) than controls. Similar proportions of survivors (71.1%) and controls (69.7%) met recommended dietary protein intake (0.8 g/kg/d). Survivors (45.4%) were less likely to report resistance training than controls (53.8%). In adjusted models, 1-g higher protein intake per kilogram of body mass per day was associated with a 7.9% increase and resistance training >=1*wk, with a 2.8% increase in lean muscle mass. LIMITATIONS: The cross-sectional study design limits temporal evaluation of the association between protein intake and lean muscle mass. CONCLUSIONS: The findings suggest that survivors of childhood ALL with low lean muscle mass may benefit from optimizing dietary protein intake in combination with resistance training. Research is needed to determine whether resistance training with protein supplementation improves lean muscle mass in survivors of childhood ALL. PMID- 26893513 TI - Financial incentives and mortality: taking pay for performance a step too far. PMID- 26893511 TI - Diaphragm Pacing as a Rehabilitative Tool for Patients With Pompe Disease Who Are Ventilator-Dependent: Case Series. AB - BACKGROUND AND PURPOSE: Pompe disease is an inherited disorder notable for severe, progressive ventilatory compromise. Although ventilatory failure has been attributed to myofiber dysfunction secondary to diaphragmatic glycogen accumulation, neural involvement of the phrenic motor system is also a prominent feature. Direct diaphragm pacing supplements respiratory function in other disorders of the phrenic motor system. Accordingly, it is hypothesized that augmented neuromuscular activity via diaphragm pacing would promote weaning from mechanical ventilation in patients with Pompe disease who are unresponsive to conventional, muscle-directed treatments. CASE DESCRIPTION: Three patients with Pompe disease developed diaphragm paresis that resulted in chronic mechanical ventilation dependence. After preoperative inspiratory muscle strengthening exercises failed to improve function, fine-wire pacing electrodes were laparoscopically implanted into the diaphragm. Diaphragm conditioning was initiated the first postoperative week and consisted of gradual increases in stimulation parameters, lengthening of stimulation sessions, and ventilator weaning. Ventilation and intramuscular electromyographic activity were recorded periodically during conditioning to quantify diaphragm neuromuscular function. OUTCOMES: During paced breathing without mechanical ventilation, tidal volumes increased, and 2 patients were weaned from daytime ventilator dependence within the first 3 months of pacing, which has been sustained over the long-term. A third patient reduced reliance on daytime ventilation, but weaning was delayed by malacia of the large airways. In all patients, pacing appeared to facilitate spontaneous phrenic motor unit activity during independent breathing without ventilator or pacer support. DISCUSSION: The findings are consistent with the view that diaphragm pacing has potential rehabilitative value to reduce reliance on mechanical ventilation in people with Pompe disease, but further study is needed. Diaphragm pacing represents a paradigm shift in the management of respiratory insufficiency for Pompe disease that warrants further controlled examination. PMID- 26893512 TI - Balancing stakeholder needs in the evaluation of healthcare quality improvement. AB - Quality improvement (QI) efforts affect a broader range of people than we often assume. These are the potential stakeholders for QI and its evaluation, and they have valuable perspectives to offer when they are consulted in planning, conducting and interpreting evaluations. QI practitioners are accustomed to consulting stakeholders to assess unintended consequences or assess patient experiences of care, but in many cases there are additional benefits to a broad inclusion of stakeholders. These benefits are better adherence to ethical standards, to assure that all legitimate interests take part, more useful and relevant evaluation information and better political buy-in to improve impact. Balancing various stakeholder needs for information requires skill for both politics and research management. These challenges have few pat answers, but several preferred practices, which are illustrated with practical examples. PMID- 26893514 TI - Towards evidence based medicine for paediatricians. PMID- 26893515 TI - QUESTION 2: Vaccinating preterm infants in resource-poor settings: what is the incidence of apnoea, bradycardia and need for respiratory support? PMID- 26893518 TI - The role of toll like receptors in giant cell arteritis. AB - GCA is a common primary systemic vasculitis that results in granulomatous inflammation of medium to large arteries. Both innate and adaptive immune mechanisms combine to drive intimal hyperplasia, luminal stenosis and ultimately occlusion. While the pathogenesis of GCA is incompletely understood, the activation of resident adventitial dendritic cells via toll like receptors (TLRs) appears to be a crucial inciting event. Here we explore the role of TLRs in the pathogenesis of GCA, including their effects on dendritic cell and T cell activation and recruitment, putative infectious triggers for GCA and the potential of TLR inhibition as a novel therapeutic strategy in GCA. PMID- 26893519 TI - Cohort study to test the predictability of the NHS Institute for Innovation and Improvement Paediatric Early Warning System. AB - OBJECTIVE: To test the predictability of the National Health Service Institute for Innovation and Improvement (NHSIII) Paediatric Early Warning System (PEWS) score to identify children at risk of developing critical illness. DESIGN: Cohort study. SETTING: Admissions to all paediatric wards at the University Hospital of Wales between 1 December 2005 and 30 November 2006. OUTCOME MEASURES: Unscheduled paediatric high dependency unit (PHDU) admission, paediatric intensive care unit (PICU) admission and death. RESULTS: There were 9075 clinical observations from 1000 children. An NHSIII PEWS score of 2 or more, which triggers review, has a sensitivity of 73.2% (95% CI 62.2% to 82.4%), specificity of 75.2% (95% CI 74.3% to 76.1%), positive predictive value (PPV) of 2.6% (95% CI 2.0% to 3.4%), negative predictive value of 99.7% (95% CI 99.5% to 99.8%) and positive likelihood ratio of 3.0 (95% CI 2.6 to 3.4) for predicting PHDU admission, PICU admission or death. Six (37.5%) of the 16 children with an adverse outcome did not have an abnormal NHSIII PEWS score. The area under the receiver operating characteristic curve for the NHSIII PEWS score was 0.83 (95% CI 0.77 to 0.88). CONCLUSIONS: The NHSIII PEWS has a low PPV and its full implementation would result in a large number of false positive triggers. The issue with PEWS scores or triggers is neither their sensitivity nor children with high scores which require clinical interventions who are not 'false positives'; but their low specificity and low PPV arising from the large number of children with low but raised scores. PMID- 26893520 TI - Variation in practice remains in the UK management of paediatric febrile neutropenia. PMID- 26893521 TI - Kerion celsi: a misdiagnosed scalp infection. PMID- 26893522 TI - QUESTION 2: Does amoxicillin exposure increase the risk of rash in children with acute Epstein-Barr virus infection? PMID- 26893523 TI - Factors That Influence the Decision to Undergo Labiaplasty: Media, Relationships, and Psychological Well-Being. AB - BACKGROUND: An increasing number of women are undergoing labiaplasty procedures; however, very little is known about the psychological factors that motivate women to seek out this procedure. OBJECTIVES: To investigate the factors that influence women's decisions to undergo labiaplasty. METHODS: Women seeking to undergo labiaplasty (n = 35) were compared with women who were not (n = 30). Standardized measures were employed to assess the patients' media exposure (television, the Internet, advertising, pornography), relationship quality, and psychological well being. RESULTS: Women's motivations for deciding to undergo a labiaplasty procedure were characterized as "appearance," "functional," "sexual," or "psychological" motivations, with concerns about the labia's appearance being the most commonly reported motivation. Correspondingly, women seeking labiaplasty were significantly less satisfied with the appearance of their genitals than the comparison group (P < .001). These women had also experienced greater exposure to images of female genitalia on the Internet (P = .004) and in advertisements (P = .021), and had internalized these images to a greater extent (P = .010). There were no differences between the two groups on the measures of relationship quality. However, significantly fewer of the women seeking to undergo a labiaplasty procedure were involved in a romantic relationship at the time of the study (P = .039). There were also no differences between the two groups on the measures of psychological well-being, except that women seeking to undergo labiaplasty were less satisfied with their lives overall (P = .027). CONCLUSIONS: The findings identified media exposure and relationship status as important factors that influence women's decisions to undergo labiaplasty. LEVEL OF EVIDENCE: 3 Risk. PMID- 26893524 TI - The Safe Labiaplasty: A Study of Nerve Density in Labia Minora and Its Implications. AB - BACKGROUND: Surgical techniques to alleviate labia minora hypertrophy are gaining popularity. Due to the rapidly growing number of labiaplasties performed around the world, there is concern for the safety of these procedures with respect to maintaining sensitivity to the genitalia and/or implications for sexual arousal. OBJECTIVES: An anatomic study aimed at identifying the nerve density distribution of the labia minora was performed to provide unique insight into performing labiaplasty while preserving sensation. METHODS: Four fresh tissue cadaver labia minora were analyzed. Each labia minora was divided into 6 anatomic areas. The samples from each of the 6 anatomic locations were analyzed for presence of nerve bundles using both a routine hematoxylin and eosin (H&E) stain and a confirmatory immunohistochemical staining for S100 protein. Nerve density was analyzed under light microscopy, counted, and then expressed as percentage nerve density as well as number of bundles per square millimeter. RESULTS: Upon gross analysis, the raw data reveal that labia minora have a heterogeneous population of sensory nerves. When looking at percent nerve density, the data do not reveal any statistical differences between the anatomic locations. CONCLUSIONS: Most labiaplasty techniques can be performed safely and are unlikely to cause loss of sensation as the nerve density distribution in labia minora is heterogeneous. PMID- 26893525 TI - Commentary on: Factors That Influence the Decision to Seek Labiaplasty: Media, Relationships, and Psychological Well-Being. PMID- 26893526 TI - Tree-based methods for individualized treatment regimes. AB - Individualized treatment rules recommend treatments on the basis of individual patient characteristics. A high-quality treatment rule can produce better patient outcomes, lower costs and less treatment burden. If a treatment rule learned from data is to be used to inform clinical practice or provide scientific insight, it is crucial that it be interpretable; clinicians may be unwilling to implement models they do not understand, and black-box models may not be useful for guiding future research. The canonical example of an interpretable prediction model is a decision tree. We propose a method for estimating an optimal individualized treatment rule within the class of rules that are representable as decision trees. The class of rules we consider is interpretable but expressive. A novel feature of this problem is that the learning task is unsupervised, as the optimal treatment for each patient is unknown and must be estimated. The proposed method applies to both categorical and continuous treatments and produces favourable marginal mean outcomes in simulation experiments. We illustrate it using data from a study of major depressive disorder. PMID- 26893527 TI - Chemical Extractability of Pb in Field-Contaminated Soils: Implications for Estimating Total Pb. AB - Lead (Pb) is frequently present in urban soils at concentrations of concern for human health. Regulations for this metal are based on total soil concentrations as determined by acid digestion, but a less expensive screening test for Pb would be useful in facilitating more thorough soil testing of urban areas if it could be shown to correlate strongly to total soil Pb. In this study, three extractants (0.1 M citrate, Modified Morgan, 1 M nitric acid) were evaluated for their ability to estimate the total Pb in contaminated soils. Nitric acid not only extracted a greater fraction of total soil Pb, but also produced the strongest correlation to total Pb and is concluded to be the superior extractant for a soil Pb screening test. As the spatial distribution of Pb was observed in selected soils to be highly heterogeneous on the micron scale, thorough soil homogenization prior to testing is recommended. PMID- 26893528 TI - How Do Spherical Diblock Copolymer Nanoparticles Grow during RAFT Alcoholic Dispersion Polymerization? AB - A poly(2-(dimethylamino)ethyl methacrylate) (PDMA) chain transfer agent (CTA) is used for the reversible addition-fragmentation chain transfer (RAFT) alcoholic dispersion polymerization of benzyl methacrylate (BzMA) in ethanol at 70 degrees C. THF GPC analysis indicated a well-controlled polymerization with molecular weight increasing linearly with conversion. GPC traces also showed high blocking efficiency with no homopolymer contamination apparent and Mw/Mn values below 1.35 in all cases. 1H NMR studies confirmed greater than 98% BzMA conversion for a target PBzMA degree of polymerization (DP) of up to 600. The PBzMA block becomes insoluble as it grows, leading to the in situ formation of sterically stabilized diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA). Fixing the mean DP of the PDMA stabilizer block at 94 units and systematically varying the DP of the PBzMA block enabled a series of spherical nanoparticles of tunable diameter to be obtained. These nanoparticles were characterized by TEM, DLS, MALLS, and SAXS, with mean diameters ranging from 35 to 100 nm. The latter technique was particularly informative: data fits to a spherical micelle model enabled calculation of the core diameter, surface area occupied per copolymer chain, and the mean aggregation number (Nagg). The scaling exponent derived from a double-logarithmic plot of core diameter vs PBzMA DP suggests that the conformation of the PBzMA chains is intermediate between the collapsed and fully extended state. This is in good agreement with 1H NMR studies, which suggest that only 5-13% of the BzMA residues of the core-forming chains are solvated. The Nagg values calculated from SAXS and MALLS are in good agreement and scale approximately linearly with PBzMA DP. This suggests that spherical micelles grow in size not only as a result of the increase in copolymer molecular weight during the PISA synthesis but also by exchange of individual copolymer chains between micelles and/or by sphere-sphere fusion events. PMID- 26893529 TI - delta13C and Water Use Efficiency in the Glucose of Annual Pine Tree Rings as Ecological Indicators of the Forests in the Most Industrialized Part of Poland. AB - In this study, stable carbon isotope ratios in the glucose samples were extracted from annual pine tree rings as bio-indicators of contemporary environmental changes in heavily urbanized areas. The sampling sites were located in close proximity to point source pollution emitters, such as a heat and power plant "Laziska" and steelworks "Huta Katowice" in Silesia (Poland). The analysed samples covered the time span from 1975 to 2012 AD, the time period of the development of industrialization and the modernization in the industrial sector in Poland, similarly as in Eastern Europe. This modernization was connected with EU legislation and the implementation of restrictive governmental regulations on emissions. The carbon isotope discrimination has been proposed as a method for evaluating water use efficiency. The measurements of carbon isotopes were carried out using the continuous flow isotope ratio mass spectrometer coupled to the elemental analyser. The delta13C values were calibrated relative to the C-3 and C 5 international standards. Diffuse air pollution caused the variation in delta13C and iWUE (the ratio between CO2 assimilation and stomatal conductance) dependency on the type of emitter and some local effects of other human activities. In this study, the first results of water use efficiency in glucose are presented. In the period of time from 1975 to 2012, the water use efficiency values increased from 98 to 122 MUmol/mol. PMID- 26893530 TI - Direct and Indirect Links between Peer Factors and Adolescent Adjustment Difficulties. AB - The purpose of the current investigation was to examine the role of emotion regulation in the link between peer factors and adolescent adjustment difficulties. The sample consisted of 206 adolescents (ages 10-18 years) and parents. Peer factors (i.e., peer antisocial behavior, peer co-rumination, peer emotion regulation) and youth depressive symptoms were based on youth reports. Youth emotion regulation and antisocial behavior were assessed using parent and youth ratings. Results showed that peer antisocial behavior was directly (but not indirectly) related to youth antisocial behavior and depressive symptoms, whereas peer emotion regulation was indirectly (but not directly) related to both adolescent outcomes. In addition, peer co-rumination was indirectly related to youth antisocial behavior and directly and indirectly related to youth depressive symptoms. In general, the results indicated little evidence of moderation by adolescent age, sex, or ethnic differences. Implications for peer relationships as socialization contexts are discussed. PMID- 26893531 TI - Evaluating the Grammars of Children Who Speak Nonmainstream Dialects of English. AB - In this article, we review three responses to the study and evaluation of grammar in children who speak nonmainstream dialects of English. Then we introduce a fourth, system-based response that views nonmainstream dialects of English, such as African American English (AAE) and Southern White English (SWE) as made up of dialect-specific and dialect-universal features. To illustrate the usefulness of a system-based approach and to distinguish our two terms from others in the dialect literature, we present AAE and SWE relative clause data from two previously published studies. Following this, we present new findings from AAE- and SWE-speaking children's use of past tense and past participles to further demonstrate the value of examining larger units (i.e., systems) of a grammar to identify a child's language strengths and weaknesses. We conclude by arguing that a system-based approach moves clinicians, educators, and researchers beyond a preoccupation with the nonmainstream aspects of children's dialects while also moving us beyond Brown's 14 morphemes. Although the focus of the article is on assessment, the content is relevant to the treatment of grammar because effective promotion of any child's grammar (including the grammars of those who speak nonmainstream dialects of English) will occur only when clinicians, educators, and researchers begin to view the child's grammar as a system rather than as a sum of its parts. PMID- 26893532 TI - Caught in the act: phenotypic consequences of a recent shift in feeding strategy of the shark barnacle Anelasma squalicola (Loven, 1844). AB - Anelasma squalicola is a barnacle found attached to deep-water lantern sharks of the family Etmopteridae and is the only known cirriped on fish hosts. While A. squalicola is equipped with mouth and thoracic appendages (cirri), which are used for suspension feeding in conventional barnacles, its attachment device (peduncle) appears to have evolved into a feeding device, embedded into the tissue of its host. Here we demonstrate, through comparisons of the feeding apparatuses between A. squalicola and conventional suspension-feeding barnacles, that mouthparts and cirri of A. squalicola are highly reduced, and incapable of suspension-feeding activities. We show that in conventional suspension-feeding barnacles strong symmetries exist within these vital trophic structures. In A. squalicola strong asymmetries are widespread, indicating that those structures have been uncoupled from natural selection. The digestive tract is consistently empty, suggesting that feeding via cirri does not occur in A. squalicola. In addition, comparisons of stable isotope ratios (delta13C and delta15N) between A. squalicola, its shark host, and a conventional suspending feeding barnacle indicate that A. squalicola is taking nutrition directly from its host shark and not from the surrounding water. Our results strongly indicate that this barnacle has abandoned suspension feeding and now solely relies on obtaining nutrition from its host by a de novo evolved feeding mechanism. PMID- 26893533 TI - Comparative morphology of the forewing base articulation in Sternorrhyncha compared with a representative of Fulgoromorpha (Insecta, Hemiptera). AB - The forewing articulation of single species from each of the four subgroups of Sternorrhyncha (Aleyrodomorpha, Aphidomorpha, Coccomorpha, Psyllomorpha) was examined by optical and scanning electron microscopy. The species were compared with a species of Cixiidae (Fulgoromorpha), as an outgroup of Sternorrhyncha. We present the results of a comparative analysis of the forewing articulation in these five groups, propose a standardized terminology and compare our findings with those previously reported. The wing base of all examined species is composed of the following structures: anterior and posterior notal wing process, first, second, and third axillary sclerites, tegula, and axillary cord. The number of elements included in the wing base and the surrounding area is the greatest in Cacopsyllamali, the most complicated species from Sternorrhyncha. Based on the shape of axillary sclerites and the number of elements forming the wing base environment, Orthezia urticae (Coccomorpha) and Cixius nervosus (Fulgoromorpha) are the most similar. Among Sternorrhyncha, the most similar axillaries are those of Aphis fabae and Orthezia urticae, which is congruent with existing classifications. In this paper we show that the four groups from Sternorrhyncha exhibit their own distinct wing base morphology. PMID- 26893534 TI - Can orbital angle morphology distinguish dogs from wolves? AB - For more than a century, the orbital angle has been studied by many authors to distinguish dog skulls from their progenitor, the wolf. In early studies, the angle was reported to be different between dogs (49 degrees -55 degrees ) and wolves (39 degrees -46 degrees ). This clear difference was, however, questioned in a more recent Scandinavian study that shows some overlap. It is clear that in all studies several methodological issues were unexplored or unclear and that group sizes and the variety of breeds and wolf subspecies were small. Archaeological dog skulls had also not been studied. Our goal was to test larger and more varied groups and add archaeological samples as they are an evolutionary stage between wolves and modern dogs. We also tested the influence of measuring methods, intra- and inter-reliability, angle symmetry, the influence of variations in skull position and the possibility of measuring and comparing this angle on 3D CT scan images. Our results indicate that there is about 50 % overlap between the angle range in wolves and modern dogs. However, skulls with a very narrow orbital angle were only found in wolves and those with a very wide angle only in dogs. Archaeological dogs have a mean angle very close to the one of the wolves. Symmetry is highest in wolves and lowest in archaeological dogs. The measuring method is very reliable, for both inter- and intra-reliability (0.99 0.97), and most skull position changes have no statistical influence on the angle measured. Three-dimensional CT scan images can be used to measure OA, but the angles differ from direct measuring and cannot be used for comparison. Evolutionary changes in dog skulls responsible for the wider OA compared to wolf skulls are mainly the lateralisation of the zygomatic process of the frontal bone. Our conclusion is that the orbital angle can be used as an additional morphological measuring method to discern wolves from recent and archaeological dogs. Angles above 60 degrees are certainly from recent dogs. Angles under 35 degrees are certainly of wolves. PMID- 26893535 TI - Identifying the role of phonology in sentence-level reading. AB - Phonological properties of the words in a sentence have been shown to affect processing fluency and comprehension. However, the exact role of phonology in sentence comprehension remains unclear. If constituents are stored in working memory during routine processing and accessed through their phonological code, phonological information may exert a pervasive influence on post-lexical comprehension processes such as retrieval for thematic integration. On the other hand, if access to constituents in memory during parsing is guided primarily by syntactic and semantic information, the parser should be isolated from phonologically based effects. In two self-paced reading experiments, we tested whether phonological overlap between distractors and a retrieval target caused retrieval interference during thematic integration. We found that phonological overlap creates difficulty during the initial encoding of the filler, but there was no evidence that phonological overlap caused later interference when the filler was retrieved for thematic integration. Despite effects at encoding, phonological interference did not have a detrimental effect on comprehension. These results suggest that phonological information is not used as a retrieval cue during routine dependency construction in incremental sentence processing. We conclude by considering the potential importance of phonology in parsing under conditions of extraordinary syntactic and/or semantic interference. PMID- 26893536 TI - On the use of the serial dilution culture method to enumerate viable phytoplankton in natural communities of plankton subjected to ballast water treatment. AB - Discharge standards for ballast water treatment (BWT) systems are based on concentrations of living cells, for example, as determined with vital stains. Ultraviolet radiation (UV) stops the reproduction of microorganisms without killing them outright; they are living, but not viable, and ecologically as good as dead. Consequently, UV-treated discharge can be compliant with the intent of regulation while failing a live/dead test. An alternative evaluation of BWT can be proposed based on the assessment of viable, rather than living, cells in discharge water. In principle, the serial dilution culture-most probable number (SDC-MPN) method provides the appropriate measure for phytoplankton. But, the method has been criticized, particularly because it is thought that many phytoplankton species cannot be cultured. A review of the literature shows that although SDC-MPN has been used for more than 50 years-generally to identify and count phytoplankton species that cannot be preserved-its application to enumerate total viable phytoplankton seems to be new, putting past criticisms of the method in a different light. Importantly, viable cells need to grow only enough to be detected, not to be brought into sustained culture, and competition between species in a dilution tube is irrelevant as long as the winner is detectable. Thorough consideration of sources of error leads to recommendations for minimizing and quantifying uncertainties by optimizing growth conditions and conducting systematic comparisons. We conclude that with careful evaluation, SDC MPN is potentially an effective method for assessing the viability of phytoplankton after BWT. PMID- 26893538 TI - Leadership, OCB and Individual Differences: Idiocentrism and Allocentrism as Moderators of the Relationship between Transformational and Transactional Leadership and OCB. AB - We propose and test a framework which suggests that the relationships between leadership styles and Organizational Citizenship Behaviors (OCB) are contingent upon employee cultural-based individual differences. More specifically, we examine whether followers' idiocentrism and allocentrism moderate the relationship between transformational and transactional leadership and followers' OCB. Survey data, collected from a sample of school teachers and their principals from the Israeli kibbutzim and urban sectors, support our hypotheses. We found the relationship between transformational leadership and OCB to be positive to the extent that allocentrism increases, and negative to the extent that idiocentrism increases. We also found the relationship between transactional leadership and OCB to be positive to the extent that idiocentrism increases and negative to the extent that allocentrism increases. Implications of these findings for research and practice are discussed. PMID- 26893537 TI - Efficient, Traceless Semi-Synthesis of alpha-Synuclein Labeled with a Fluorophore/Thioamide FRET Pair. AB - We have shown that thioamides can be incorporated into proteins through semi synthesis and used as probes to monitor structural changes. To date, our methods have required the presence of a cysteine at the peptide ligation site, which may not be present in the native peptide sequence. Here, we present a strategy for the semi-synthesis of thioproteins using homocysteine as a ligation point with subsequent masking as methionine, making the ligation "traceless." PMID- 26893539 TI - The emotional and physical impact of wet age-related macular degeneration: findings from the wAMD Patient and Caregiver Survey. AB - OBJECTIVES: This was a cross-sectional survey to evaluate the physical and emotional impact of wet age-related macular degeneration (wAMD) on a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections, and caregivers (paid and unpaid). METHODS: The survey was performed in nine countries using an ophthalmologist-devised questionnaire. RESULTS: A total of 910 patients and 890 caregivers completed the questionnaire. Most patients had been diagnosed and receiving antivascular endothelial growth factor injections for more than 1 year (74.7% and 63.8%, respectively), and many patients (82.1%) received support from a caregiver (usually a child/grandchild [47.3%] or partner [23.3%]). wAMD had a negative impact on most patients (71.6%); many rated fear (44.9%), sadness (39.9%), frustration (37.3%), and depression (34.0%) as common. It was linked to physical consequences, such as difficulty in reading (61.1%). Many effects were significantly greater in patients with a longer duration of disease or with wAMD in both eyes. Some caregivers (unpaid) also reported that caregiving had a negative impact on them (31.1%); many reported emotions such as sadness (34.9%) and depression (24.4%), but many also felt useful (48.4%). Overall, 27.2% of caregivers (unpaid) rated caregiving as inconvenient; this was linked to days of employment/personal obligations missed. CONCLUSION: wAMD has a significant negative impact on the lives of patients, including vision-related depression, poor mobility, and limitations in day-to-day activities. The impact on nonprofessional caregivers may be underestimated in terms of emotional impact (such as depression) and loss of productivity. PMID- 26893540 TI - Comparison between the EX-PRESS P-50 implant and trabeculectomy in patients with open-angle glaucoma. AB - PURPOSE: To evaluate the EX-PRESS P-50 implant compared to standard trabeculectomy (TBC). METHODS: Single-center prospective randomized study; 20 eyes of 20 patients were treated with the EX-PRESS P-50 implant, and 20 eyes of 20 patients with TBC, over a 19-month period. Records of all patients were reviewed and compared. Success was defined as intraocular pressure (IOP) <21 and >5 mmHg or a decrease of 30% of IOP. Failure was defined as >21 mmHg or decline in visual acuity. Statistical analysis was made with Student's t-test and chi (2) test analyzed with SPSS version 13.0. RESULTS: The average follow-up was 8.6 months (+/-4.9 months) for the EX-PRESS P-50 group and 9.6 months (+/-5.3 months) for the TBC group. The postoperative visual acuity and IOP were not significantly different. We report more complications in the EX-PRESS P-50 group. At 3, 6, and 12 months follow-up, the control group was found to be free of complications, whereas multiple complications were observed in the EX-PRESS P-50 group at 3 and 6 months follow-up. We found no differences in either group with respect to success. CONCLUSION: Both procedures are equally effective for the treatment of glaucoma, with 80% success in the EX-PRESS P-50 group and 72.7% in the control group. PMID- 26893542 TI - Antiviral therapy: a perspective. AB - This paper discusses extracorporeal removal of viral particles and their antigens from the blood as an auxiliary therapy. This hypothesis has not been reported before. In some chronic blood-borne viral infections, the virus remains systemic and persistent for extended periods of time, with adverse effects that weaken the immune system. Blood titers of virus and its toxins are proportional to the severity of the disease, and their reduction can alleviate symptoms, leading to improved health. Several blood-borne viral infections can be overcome by the young, but are life-threatening in the elderly. It is known that some older people have extreme difficulty tolerating viral infections such as influenza and the common cold. Further, several types of viral infection persist throughout the life of the individual and cannot be eliminated by conventional treatments. Well known infections of this type include HIV and hepatitis B. In the case of Ebola virus, patients remain infectious as long as their blood contains the virus. According to the present hypothesis, an extracorporeal viral antibody column (EVAC) is proposed for elimination or reduction of the blood viral titer when treating blood-borne viral infection. EVAC would selectively trap viral antigens and toxins in the blood into an extracorporeal circuit, while returning detoxified blood back to the patient's body. It is anticipated that EVAC would reduce mortality caused by blood-borne viral infections in the elderly since reduction of blood virus titers would improve health, leading to improved overall patient performance. Such enhancement would also make conventional therapies even more effective. EVAC could have a lifesaving role in treatment of viral illness, especially those involving lethal viruses such as Ebola, where the patient's recovery to a large extent depends on their general health status. EVAC would be for single use and appropriately disposed of after each detoxification procedure. When sufficient research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections. PMID- 26893543 TI - Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson's rats. AB - L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective therapy for Parkinson's disease (PD), but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID). Enhanced function of dopamine D1 receptor (D1R) and N-methyl-D aspartate receptor (NMDAR) is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1) interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2). In this study, we demonstrated in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson's patients. PMID- 26893544 TI - Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species. AB - Curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34(+) cells, and granulocytes were incubated for 4 or 24 hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23 days and etoposide was administered for the final 3 days of the experiment. Curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34(+) cells and granulocytes. Curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P<0.05) and induced apoptosis of BNML cells more efficiently than etoposide alone (1.54-fold change versus etoposide alone; P<0.05), but this treatment protected nonleukemic B-cells from apoptosis. Thus, curcumin can increase the antileukemic effect of etoposide through reactive oxygen species in sensitive myeloid leukemia cells, and it is harmless to normal human cells. PMID- 26893541 TI - Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion dependent thalassemia syndromes. AB - The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30-40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO-L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption. PMID- 26893545 TI - Establishment of a novel therapeutic vector targeting the trigeminal ganglion in rats. AB - BACKGROUND: In the pathogenesis of herpes simplex keratitis, herpes simplex virus type 1 (HSV-1) infection begins in corneal epithelium cells and then progresses through the sensory nerve endings and finally travels up forward to the trigeminal ganglion (TG), where it remains as latent virus. The available anti HSV therapies do not completely suppress the recurrence of active HSV-1 infection. The aim of this study was to establish a novel replication-defective (rd) HSV-1 (rdHSV) vector (rdHSV-interferon gamma [IFNgamma]) that could effectively target the TG. METHODS: Recombinant HSV-1 virus was inserted into a shuttle plasmid carrying IFNgamma to establish the rdHSV-IFNgamma vector. Safety was evaluated in vitro by 50% cellular cytotoxicity in transfected SH-SY5Y neuroblastoma cells and in vivo by Kaplan-Meier survival estimate and infection rate. Wistar rats were immunized with rdHSV-IFNgamma to evaluate the TG targeting efficiency. Real-time polymerase chain reaction and Western blot assays were used to evaluate IFNgamma mRNA and protein expression and rdHSV-IFNgamma localization. RESULTS: The rdHSV-IFNgamma vector was successfully constructed and showed high in vitro safety and overall survival and a corneal infection rate similar to that of control rats immunized with saline (control group; P>0.05). Real-time polymerase chain reaction and immunohistochemistry assays confirmed IFNgamma expression and effective TG targeting on days 14 and 21, which increased with postimmunization time. Moreover, IFNgamma was expressed sufficiently in the TG tissues. CONCLUSION: The rdHSV-IFNgamma can act as an effective gene transporting vector that carries the therapeutic genes to the TG and triggers its expression. PMID- 26893546 TI - Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis. AB - BACKGROUND: Limited data are available on mesalamine (5-aminosalicylic acid; 5 ASA) use in pediatric ulcerative colitis (UC). AIM: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once daily, oral administration of multimatrix mesalamine to children and adolescents with UC. METHODS: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. RESULTS: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac 5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. CONCLUSION: Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5 ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844. PMID- 26893547 TI - Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting. AB - BACKGROUND: Adverse drug reactions (ADRs) have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system. METHODS: Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261) completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history. RESULTS: Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts. CONCLUSION: We may draw a profile of rheumatological patients willing to report ADRs: 1) The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2) They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3) They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients' reporting of potential ADRs. PMID- 26893548 TI - Optimal breast cancer screening strategies for older women: current perspectives. AB - Breast cancer is a major cause of cancer-related deaths among older women, aged 65 years or older. Screening mammography has been shown to be effective in reducing breast cancer mortality in women aged 50-74 years but not among those aged 75 years or older. Given the large heterogeneity in comorbidity status and life expectancy among older women, controversy remains over screening mammography in this population. Diminished life expectancy with aging may decrease the potential screening benefit and increase the risk of harms. In this review, we summarize the evidence on screening mammography utilization, performance, and outcomes and highlight evidence gaps. Optimizing the screening strategy will involve separating older women who will benefit from screening from those who will not benefit by using information on comorbidity status and life expectancy. This review has identified areas related to screening mammography in older women that warrant additional research, including the need to evaluate emerging screening technologies, such as tomosynthesis among older women and precision cancer screening. In the absence of randomized controlled trials, the benefits and harms of continued screening mammography in older women need to be estimated using both population-based cohort data and simulation models. PMID- 26893549 TI - Reasons for elderly patients GP visits: results of a cross-sectional study. AB - OBJECTIVE: The aim of this study is to describe the frequency of reasons for elderly patients visits to a general practice (GP) setting. SUBJECTS AND METHODS: Cross-sectional data from 8,877 randomly selected patients were assessed during a 1-year period by 209 GPs in the German federal state of Saxony. The reasons for visits, performed procedures, and results of visits were documented. In this study, the data of patients aged 65 years and older are analyzed and the procedural and nonprocedural reasons for visits are described. RESULTS: In all, 2,866 patients aged 65 years and older were included. The majority of patients (1,807) were female. A total of 4,426 reasons for visits were found, distributed on 363 International Classification of Primary Care-2 codes. In the mean, there were 1.5 reasons for a GP visit from each patient. The top five nonprocedural reasons for visiting the GP were: cough (1.8%), back complaints (1.6%), shoulder complaints (1.3%), knee complaints (1.1%), and dyspnea (1.0% of all reasons for visit). The top five procedural reasons for visiting the GP included follow-up investigations of cardiovascular or endocrine disorders and immunizations. The top 30 nonprocedural reasons for visits covered 21.9% of all reasons for visiting. The top 30 procedural reasons covered 54.3% of all reasons for visits. CONCLUSION: The current work indicates that people aged 65 years and older consult the GP more frequently for procedural than for nonprocedural reasons. The top 30 procedural and nonprocedural reasons for visits cover ~75% of all reasons for visits in these patients. PMID- 26893550 TI - Association of incidental emphysema with annual lung function decline and future development of airflow limitation. AB - OBJECTIVES: Emphysema is one of the prognostic factors for rapid lung function decline in patients with COPD, but the impact of incidentally detected emphysema on population without spirometric abnormalities has not been evaluated. This study aimed to determine whether emphysema detected upon computed tomography (CT) screening would accelerate the rate of lung function decline and influence the possibility of future development of airflow limitation in a population without spirometric abnormalities. MATERIALS AND METHODS: Subjects who participated in a routine screening for health checkup and follow-up pulmonary function tests for at least 3 years between 2004 and 2010 were retrospectively enrolled. The percentage of low-attenuation area below -950 Hounsfield units (%LAA-950) was calculated automatically. A calculated value of %LAA-950 that exceeded 10% was defined as emphysema. Adjusted annual lung function decline was analyzed using random-slope, random-intercept mixed linear regression models. RESULTS: A total of 628 healthy subjects within the normal range of spriometric values were included. Multivariable analysis showed that the emphysema group exhibited a faster decline in forced vital capacity (-33.9 versus -18.8 mL/year; P=0.02). Emphysema was not associated with the development of airflow limitation during follow-up. CONCLUSION: Incidental emphysema quantified using CT scan was significantly associated with a more rapid decline in forced vital capacity in the population with normative spirometric values. However, an association between emphysema and future development of airflow limitation was not observed. PMID- 26893551 TI - The lung function profile of once-daily tiotropium and olodaterol via Respimat((r)) is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler((r)) (ENERGITO((r)) study). AB - BACKGROUND: Tiotropium + olodaterol has demonstrated improvements beyond lung function benefits in a large Phase III clinical program as a once-daily maintenance treatment for COPD and may be a potential option for the initiation of maintenance treatment in COPD. Despite guideline recommendations that combined long-acting beta2-agonists and inhaled corticosteroids should only be used in individuals at high risk of exacerbation, there is substantial use in individuals at lower risk. This raises the question of the comparative effectiveness of this combination as maintenance treatment in this group compared to other combination regimens. OBJECTIVE: The study aimed to assess the effect on lung function of once-daily tiotropium + olodaterol versus twice-daily salmeterol + fluticasone propionate in all participants with Global initiative for chronic Obstructive Lung Disease 2 or 3 (moderate to severe) COPD. METHODS: This was a randomized, double-blind, double-dummy, four-treatment, complete crossover study in which participants received once-daily tiotropium + olodaterol (5/5 ug and 2.5/5 ug) via Respimat((r)) and twice-daily salmeterol + fluticasone propionate (50/500 ug and 50/250 ug) via Accuhaler((r)) for 6 weeks. The primary end point was change in forced expiratory volume in 1 second (FEV1) area under the curve from 0 hour to 12 hours (AUC0-12) relative to the baseline after 6 weeks. RESULTS: Tiotropium + olodaterol 5/5 ug and 2.5/5 ug demonstrated statistically significant improvements in FEV1 AUC0-12 compared to salmeterol + fluticasone propionate (improvements from baseline were 317 mL and 295 mL with tiotropium + olodaterol 5/5 ug and 2.5/5 ug, and 188 mL and 192 mL with salmeterol + fluticasone propionate 50/500 ug and 50/250 ug, respectively). Tiotropium + olodaterol was superior to salmeterol + fluticasone propionate in lung function secondary end points, including FEV1 area under the curve from 0 hour to 24 hours (AUC0-24). CONCLUSION: Once-daily tiotropium + olodaterol in participants with moderate-to severe COPD provided superior lung function improvements to twice-daily salmeterol + fluticasone propionate. Dual bronchodilation can be considered to optimize lung function in individuals requiring maintenance treatment for COPD. PMID- 26893552 TI - "Frequent exacerbator" is a phenotype of poor prognosis in Japanese patients with chronic obstructive pulmonary disease. AB - BACKGROUND: The prognosis of Japanese patients with COPD who suffer repeated exacerbations is unclear, although Westerners with such episodes have a poor prognosis. MATERIALS AND METHODS: We conducted a 1-year prospective observational trial involving 90 Japanese patients with COPD: 58 nonexacerbators, 12 infrequent exacerbators, and 20 frequent exacerbators classified on the basis of exacerbation frequency (zero, one, and two or more exacerbations/year), respectively, during the previous year were observed prospectively for 1 year. The characteristics of frequent exacerbators, the frequency of exacerbation, and the period until the first event were then compared among the groups. RESULTS: A total of 78 patients completed the study. Frequent exacerbators had a significantly higher risk of frequent exacerbation in the following year than the case for nonexacerbators (odds ratio [95% confidence interval] 2.94 [1.21-7.17], P=0.0340), but not in comparison with infrequent exacerbators (1.51 [0.49-4.63], P>0.05). The mean annual frequency of exacerbations in the following year was significantly (P=0.0020) higher in the frequent exacerbators (1.4 exacerbations/year) than in the nonexacerbators (0.4), but not in the infrequent exacerbators (0.9, P>0.05). The mean period until the first exacerbation was significantly shorter in the frequent exacerbators than in the infrequent or nonexacerbators (P=0.0012). Independent risk factors for future frequent exacerbation included the presence of gastroesophageal reflux disease, more severe airflow obstruction, and use of inhaled corticosteroids. CONCLUSION: Our present results indicate that Japanese COPD patients suffering frequent exacerbation have a poor prognosis. The characteristics of Japanese and Western COPD patients suffering frequent exacerbation are similar. PMID- 26893553 TI - No association between exacerbation frequency and stroke in patients with COPD. AB - BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have a higher risk of stroke than the general population. Chronic inflammation associated with COPD is thought to contribute to this risk. Exacerbations of COPD are associated with a rise in inflammation, suggesting that there may be an association between exacerbation frequency and the risk of stroke. This study examined that association. METHODS: Using the UK Clinical Practice Research Datalink, COPD patients with a first stroke between January 2004 and December 2013 were identified as cases and matched on age, sex, and general practice to controls with COPD but without a stroke (6,441 cases and 19,323 controls). Frequent exacerbators (FEs) were defined as COPD patients with >=2 exacerbations, and infrequent exacerbators (IEs) have <=1 exacerbation in the year prior to their stroke. Conditional logistic regression was used to estimate the association between exacerbation frequency and stroke overall, and by stroke subtype (hemorrhagic, ischemic, or transient ischemic attack). Exacerbations were also categorized into 0, 1, 2, or >=3 exacerbations in the year prior to stroke. RESULTS: There was no evidence that FE had an increased odds of stroke compared to IE (OR [odds ratio] =0.95, 95% CI [confidence interval] =0.89-1.01). There was strong evidence that the risk of stroke decreased with each exacerbation of COPD experienced per year (P trend =0.003). In the subgroup analysis investigating stroke subtype, FE had 33% lower odds of hemorrhagic stroke than IE (OR =0.67, 95% CI =0.51-0.88, P=0.003). No association was found within other stroke types. CONCLUSION: This study found no evidence of a difference in the odds of stroke between IE and FE, suggesting that exacerbation frequency is unlikely to be the reason for increased stroke risk among COPD patients. Further research is needed to explore the association through investigation of stroke risk and the severity, duration, treatment of exacerbations, and concurrent treatment of cardiovascular risk factors. PMID- 26893554 TI - Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells. AB - BACKGROUND: Cigarette smoke (CS) increases oxidative stress (OS) in the lungs. Pomegranate juice (PJ) possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549). METHODS: Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week). PJ groups received daily 80 MUmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1) expression levels of inflammatory markers, 2) apoptosis, 3) OS, and 4) histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 MUM) or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining. RESULTS: Acutely, a significant increase in interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months), increased expression of TNF-alpha was observed, and lung sections demonstrated emphysematous changes when compared to Control. PJ supplementation to CS animals attenuated the increased expression of TNF-alpha and normalized lung cytoarchitecture. At the cellular level, CS extract reduced cellular proliferation and triggered cellular death. Pretreatment with PJ attenuated the damaging effects of CS extract on cultured human alveolar cells. CONCLUSION: The expression of inflammatory mediators associated with CS exposure and the emphysematous changes noted with chronic CS exposure were reduced with PJ supplementation. In vitro, PJ attenuated the damaging effects of CS extract on cultured human alveolar cells. PMID- 26893556 TI - Preclinical animal study and human clinical trial data of co-electrospun poly(L lactide-co-caprolactone) and fibrinogen mesh for anterior pelvic floor reconstruction. AB - Synthetic and biological materials are commonly used for pelvic floor reconstruction. In this study, host tissue response and biomechanical properties of mesh fabricated from co-electrospun poly(L-lactide-co-caprolactone) (PLCL) and fibrinogen (Fg) were compared with those of polypropylene mesh (PPM) in a canine abdominal defect model. Macroscopic, microscopic, histological, and biomechanical evaluations were performed over a 24-week period. The results showed that PLCL/Fg mesh had similar host tissue responses but better initial vascularization and graft site tissue organization than PPM. The efficacy of the PLCL/Fg mesh was further examined in human pelvic floor reconstruction. Operation time, intraoperative blood loss, and pelvic organ prolapse quantification during 6 month follow-up were compared for patients receiving PLCL/Fg mesh versus PPM. According to the pelvic organ prolapse quantification scores, the anterior vaginal wall 3 cm proximal to the hymen point (Aa point), most distal edge of the cervix or vaginal cuff scar point (C point), and posterior fornix point (D point) showed significant improvement (P<0.01) at 1, 3, and 6 months for both groups compared with preoperatively. At 6 months, improvements at the Aa point in the PLCL/Fg group were significantly more (P<0.005) than the PPM group, indicating that, while both materials improve the patient symptoms, PLCL/Fg mesh resulted in more obvious improvement. PMID- 26893555 TI - Determinants of change in physical activity during moderate-to-severe COPD exacerbation. AB - BACKGROUND: Data are scarce on patient physical activity (PA) level during exacerbations of chronic obstructive pulmonary disease (eCOPD). The objective of the study was to evaluate the level and determinants of change in PA during an eCOPD. MATERIALS AND METHODS: We conducted a prospective cohort study with recruitment from emergency departments (EDs) of 16 participating hospitals from June 2008 to September 2010. Data were recorded on socioeconomic characteristics, dyspnea, forced expiratory volume in 1 second (FEV1%), comorbidities, health related quality of life, factors related to exacerbation, and PA in a stable clinical condition and during the eCOPD episode. RESULTS: We evaluated 2,487 patients. Common factors related to the change in PA during hospital admission or 7 days after discharge to home from the ED were lower PA at baseline and during the first 24 hours after the index evaluation. Age, quality of life, living alone, length of hospital stay, and use of anticholinergic or systemic corticosteroids in treating the exacerbation were associated with the change in PA among hospitalized patients. Predictors of change among patients not admitted to hospital were baseline FEV1% and dyspnea at rest on ED arrival. CONCLUSION: Among the patients evaluated in an ED for an eCOPD, the level and change in PA was markedly variable. Factors associated with exacerbation (PA 24 hours after admission, medication during admission, and length of hospital stay) and variables reflecting patients' stable clinical condition (low level of PA, age, quality of life, FEV1%) are predictors of the change in PA during a moderate-to severe eCOPD. PMID- 26893557 TI - Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia. AB - Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX-MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX-MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX-MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX-MNP and hyperthermal treatment, compared with MTX or thermo-therapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished - even after its combination with MNP and/or hyperthermia - and the application of higher thermal dosages might be necessary. PMID- 26893559 TI - Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation. AB - In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability. PMID- 26893558 TI - Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene. AB - Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin-polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66+/-4.5 nm and a zeta potential of 27.1+/-1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy. PMID- 26893561 TI - Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride. AB - OBJECTIVES: The study aims at applying pharmaceutical nanotechnology and D optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride-Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel. METHODS: Sixteen nanoparticle formulations were prepared by liquid-liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate. RESULTS: Through the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased. CONCLUSION: This approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness. PMID- 26893560 TI - Cytotoxicity of CdTe quantum dots in human umbilical vein endothelial cells: the involvement of cellular uptake and induction of pro-apoptotic endoplasmic reticulum stress. AB - Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (-21.63+/-0.91 mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95.52% by energy depletion (NaN3/deoxyglucose or low temperature). The endocytosis inhibitors (methyl-beta-cyclodextrin, genistein, sucrose, chlorpromazine, and colchicine) dramatically decreased the uptake of CdTe QDs by HUVECs, suggesting that both caveolae/raft- and clathrin-mediated endocytosis were involved in the endothelial uptake of CdTe QDs. Using immunocytochemistry, a striking overlap of the internalized CdTe QDs and ER marker was observed, which indicates that QDs may be transported to ER. The CdTe QDs also caused remarkable ER stress responses in HUVECs, confirmed by significant dilatation of ER cisternae, upregulation of ER stress markers GRP78/GRP94, and activation of protein kinase RNA-like ER kinase-eIF2alpha-activating transcription factor 4 pathway (including phosphorylation of both protein kinase RNA-like ER kinase and eIF2alpha and elevated level of activating transcription factor 4). CdTe QDs further promoted an increased C/EBP homologous protein expression, phosphorylation of c-JUN NH2-terminal kinase, and cleavage of ER-resident caspase 4, while the specific inhibitor (SP600125, Z-LEVD-fmk, or salubrinal) significantly attenuated QDs-triggered apoptosis, indicating that all three ER stress-mediated apoptosis pathways were activated and the direct participation of ER in the CdTe QDs-caused apoptotic cell death in HUVECs. Our findings provide important new insights into QDs toxicity and reveal potential cardiovascular risks for the future applications of QDs. PMID- 26893562 TI - Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization. AB - For the first time, we coupled reduced detonation nanodiamonds (NDs) with a plant secondary metabolite, citropten (5,7-dimethoxycoumarin), and demonstrated how this complex was able to reduce B16F10 tumor cell growth more effectively than treatment with the pure molecule. These results encouraged us to find out the specific mechanism underlying this phenomenon. Internalization kinetics and quantification of citropten in cells after treatment with its pure or ND conjugated form were measured, and it was revealed that the coupling between NDs and citropten was essential for the biological properties of the complex. We showed that the adduct was not able to induce apoptosis, senescence, or differentiation, but it determined cell cycle arrest, morphological changes, and alteration of mRNA levels of the cytoskeletal-related genes. The identification of metaphasic nuclei and irregular disposition of beta-actin in the cell cytoplasm supported the hypothesis that citropten conjugated with NDs showed antimitotic properties in B16F10 cells. This work can be considered a pioneering piece of research that could promote and support the biomedical use of plant drug functionalized NDs in cancer therapy. PMID- 26893564 TI - Neuroleptic-induced deficit syndrome in bipolar disorder with psychosis. AB - Neuroleptics can induce not only physical adverse effects but also mental effects that produce deficit status in thought, affect, cognition, and behavior. This condition is known as neuroleptic-induced deficit syndrome (NIDS), which includes apathy, lack of initiative, anhedonia, indifference, blunted affect, and reduced insight into disease. Although this old concept now appears almost forgotten, neuroleptics, whether typical or atypical, can make depression or bipolar disorder resemble other more refractory conditions, readily leading to mistaken diagnosis and inappropriate treatment. The authors describe three cases of NIDS superimposed on depressive phase in bipolar disorder with psychosis, where the attending psychiatrist's failure to recognize NIDS prevented patients from receiving effective treatment and achieving remission. All cases achieved remission after reduction of neuroleptics and intensive therapy, including electroconvulsive therapy, for bipolar depression. The concept of NIDS was originally introduced for schizophrenia, and it has rarely been highlighted in other diseases. In recent years, however, atypical antipsychotics are being more often administered to patients with bipolar disorder. Psychiatrists, therefore, should also remember and exercise caution regarding NIDS in the pharmacotherapy of bipolar disorder with and without psychosis. The authors believe that the concept of NIDS needs to be reappraised in current psychiatry. PMID- 26893563 TI - Peen treatment on a titanium implant: effect of roughness, osteoblast cell functions, and bonding with bone cement. AB - Implant failure due to poor integration of the implant with the surrounding biomaterial is a common problem in various orthopedic and orthodontic surgeries. Implant fixation mostly depends upon the implant surface topography. Micron to nanosize circular-shaped groove architecture with adequate surface roughness can enhance the mechanical interlock and osseointegration of an implant with the host tissue and solve its poor fixation problem. Such groove architecture can be created on a titanium (Ti) alloy implant by laser peening treatment. Laser peening produces deep, residual compressive stresses in the surfaces of metal parts, delivering increased fatigue life and damage tolerance. The scientific novelty of this study is the controlled deposition of circular-shaped rough spot groove using laser peening technique and understanding the effect of the treatment techniques for improving the implant surface properties. The hypothesis of this study was that implant surface grooves created by controlled laser peen treatment can improve the mechanical and biological responses of the implant with the adjoining biomaterial. The objective of this study was to measure how the controlled laser-peened groove architecture on Ti influences its osteoblast cell functions and bonding strength with bone cement. This study determined the surface roughness and morphology of the peen-treated Ti. In addition, this study compared the osteoblast cell functions (adhesion, proliferation, and differentiation) between control and peen-treated Ti samples. Finally, this study measured the fracture strength between each kind of Ti samples and bone cement under static loading. This study found that laser peen treatment on Ti significantly changed the surface architecture of the Ti, which led to enhanced osteoblast cell adhesion and differentiation on Ti implants and fracture strength of Ti-bone cement interfaces compared with values of untreated Ti samples. Therefore, the laser peen treatment method has the potential to improve the biomechanical functions of Ti implants. PMID- 26893566 TI - Chronic organophosphate-induced neuropsychiatric disorder: a case report. AB - Chronic organophosphate (OP)-induced neuropsychiatric disorder is a rare condition following prolonged exposure to OP compounds. Due to the lack of valid diagnostic tools and criteria, very few cases are seen in clinical practice and are often misdiagnosed. Misdiagnosis can lead to inappropriate treatment that may increase the risk of morbidity or suicidality. In this paper, we present the case of a 35-year-old male who needed support in breathing from a mechanical ventilator and developed neuropsychiatric behavioral problems following ingestion of OP compounds, which lead to suicidality. The patient was treated by the psychiatric team with antipsychotic and antidepressants and improved following the regular use of medication. PMID- 26893565 TI - Depot-medication compliance for patients with psychotic disorders: the importance of illness insight and treatment motivation. AB - BACKGROUND: Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. METHODS: Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. RESULTS: Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. CONCLUSION: Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot medication compliance. Possible implications for clinical practice are discussed. PMID- 26893567 TI - Sudoscan as a noninvasive tool to assess sudomotor dysfunction in patients with Fabry disease: results from a case-control study. AB - Hypohidrosis is a frequent and early symptom in patients with Fabry disease. Studies have reported improved sweating in patients treated with enzyme replacement therapy. A new method, Sudoscan, has been developed that is noninvasive, is quantitative, and can quickly evaluate sweat gland function. It is based on the electrochemical reaction between sweat chlorides and stainless steel electrodes in contact with the palms and soles. The aim of our study was to evaluate the Sudoscan as a tool to assess sudomotor dysfunction in patients with Fabry disease. Consecutive patients were prospectively recruited who had a diagnosis of Fabry disease, which had been confirmed genetically and/or by measurement of alpha-galactosidase activity in leukocytes. Healthy controls, matched (1:1) for age and sex, were also enrolled. Test results were expressed immediately as electrochemical skin conductance (ESC, uS) for hands and feet. Sudomotor dysfunction was considered absent, moderate, or severe if the ESC measured on the feet was >60 uS, between 60 and 40 uS, or <40 uS, respectively. Among the 18 patients, 11 had hypohidrosis or anhidrosis. Hand and feet ESCs were significantly lower in patients compared to their controls (P=0.0015 and P=0.0047, respectively). Among patients, 8/18 (44.5%) had a sudomotor dysfunction, moderate in three and severe in five cases. Hand and feet ESCs were significantly lower in those with hypohidrosis/anhidrosis compared to those without (P=0.0014 and P=0.0056, respectively). This study showed that Sudoscan provided a quick, noninvasive, and quantitative measurement of sudomotor function in Fabry disease patients. PMID- 26893569 TI - Retraction. AB - [This retracts the article on p. 3507 in vol. 8, PMID: 26648742.]. PMID- 26893570 TI - Retraction. AB - [This retracts the article on p. 2215 in vol. 8, PMID: 26345468.]. PMID- 26893568 TI - The cost of inpatient death associated with acute coronary syndrome. AB - BACKGROUND: No studies have addressed the cost of inpatient mortality during an acute coronary syndrome (ACS) admission. OBJECTIVE: Compare ACS-related length of stay (LOS), total admission cost, and total admission cost by day of discharge/death for patients who died during an inpatient admission with a matched cohort discharged alive following an ACS-related inpatient stay. METHODS: Medical and pharmacy claims (2009-2012) were used to identify admissions with a primary diagnosis of ACS from patients with at least 6 months of continuous enrollment prior to an ACS admission. Patients who died during their ACS admission (deceased cohort) were matched (one-to-one) to those who survived (survived cohort) on age, sex, year of admission, Chronic Condition Index score, and prior revascularization. Mean LOS, total admission cost, and total admission cost by the day of discharge/death for the deceased cohort were compared with the survived cohort. A generalized linear model with log transformation was used to estimate the differences in the total expected incremental cost of an ACS admission and by the day of discharge/death between cohorts. A negative binomial model was used to estimate differences in the LOS between the two cohorts. Costs were inflated to 2013 dollars. RESULTS: A total of 1,320 ACS claims from patients who died (n=1,320) were identified and matched to 1,319 claims from the survived patients (n=1,319). The majority were men (68%) and mean age was 56.7+/-6.4 years. The LOS per claim for the deceased cohort was 47% higher (adjusted incidence rate ratio: 1.47, 95% confidence interval: 1.37-1.57) compared with claims from the survived cohort. Compared with the survived cohort, the adjusted mean incremental total cost of ACS admission claims from the deceased cohort was US$43,107+/-US$3,927 (95% confidence interval: US$35,411-US$50,803) higher. CONCLUSION: Despite decreasing ACS hospitalizations, the economic burden of inpatient death remains high. PMID- 26893571 TI - Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol. AB - PURPOSE: Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA) is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG) microspheres with adsorbed SIgA on MCF-7 human breast cancer cells. METHODS: The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre incubated for 24 hours with or without SIgA (100 ng/mL), PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL). Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry. RESULTS: Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca(2+) levels. In the presence of SIgA, an increase in the percentage of apoptotic cells was observed. The highest apoptosis index was observed when the cells were treated with PEG microspheres with adsorbed SIgA. CONCLUSION: These data suggest that colostral SIgA adsorbed to PEG microspheres has antitumor effects on human MCF-7 breast cancer cells and that the presence of large amounts of this protein in secreted breast milk may provide protection against breast tumors in women who breastfed. PMID- 26893572 TI - Potassium-3-beta-hydroxy-20-oxopregn-5-en-17-alpha-yl sulfate: a novel inhibitor of 78 kDa glucose-regulated protein. AB - BACKGROUND: Previous studies have shown the central role of 78 kDa glucose regulated protein (GRP78) in colorectal cancer (CRC) survival and chemoresistance. In the present study, we aimed to design a GRP78 inhibitor and test its potential to inhibit CRC cells growth. MATERIALS AND METHODS: Computer aided drug design was used to establish novel compounds as potential inhibitors of GRP78. Discovery Studio 3.5 software was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the protein. The cytotoxicity of the designed compounds was evaluated using the MTT assay and the propidium iodide method. The effect of the inhibitor on the expression of GRP78 was evaluated by immunoblotting. RESULTS: Among the designed compounds, only potassium-3-beta-hydroxy-20-oxopregn-5-en-17-alpha-yl sulfate (PHOS) has a potential to inhibit the growth of CRC cells. Inhibition of cellular growth was largely attributed to downregulation of GRP78 and induction of apoptotic cell death. CONCLUSION: These results introduce PHOS as a promising GRP78 inhibitor that could be used in future studies as a combination with chemotherapy in the treatment of CRC patients. Our ongoing studies aim to characterize PHOS safety profile as well as its mechanism of action. PMID- 26893573 TI - Radix Tetrastigma hemsleyani flavone inhibits proliferation, migration, and invasion of human lung carcinoma A549 cells. AB - Radix Tetrastigma hemsleyani flavone (RTHF) is widely used as a traditional herb and has detoxification and anti-inflammatory effects. In this study, we investigated the potential effects of RTHF on the growth and metastasis of human lung adenocarcinoma A549 cells and evaluated its mechanisms. A549 cells were treated with RTHF at various concentrations for different periods. In vitro Cell Counting Kit-8 assay and colony formation methods showed that RTHF had dose- and time-dependent antiproliferation effects on A549 cells. A cell adhesion assay showed that RTHF decreased A549 cell adhesion in a dose-dependent manner. Cell invasion and migration were investigated using the Transwell assay and observed using an inverted microscope; the results showed that cell metastasis was significantly lower in the treatment group than that in the control group (P<0.01). Expression of metastasis-related matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) was detected by real-time polymerase chain reaction and Western blotting. The results showed that the expression of MMP-2, MMP-9, and TIMP-1 decreased, while that of TIMP-2 increased significantly in the RTHF group when compared with the results of the control group. These results show that RTHF exhibits antigrowth and antimetastasis activity in lung cancer A549 cells by decreasing the expression of MMP-2/-9 and TIMP-1 and increasing that of TIMP-2. PMID- 26893575 TI - Candidate genes of idiopathic pulmonary fibrosis: current evidence and research. AB - Idiopathic pulmonary fibrosis (IPF) is a group of common and lethal forms of idiopathic interstitial pulmonary disease. IPF is characterized by a progressive decline in lung function with a median survival of 2-3 years after diagnosis. Although the pathogenesis of the disease remains unknown, genetic predisposition could play a causal role in IPF. A set of genes have been identified as candidate genes of IPF in the past 20 years. However, the recent technological advances that allow for the analysis of millions of polymorphisms in different subjects have deepened the understanding of the genetic complexity of IPF susceptibility. Genome-wide association studies and whole-genome sequencing continue to reveal the genetic loci associated with IPF risk. In this review, we describe candidate genes on the basis of their functions and aim to gain a better understanding of the genetic basis of IPF. The discovered candidate genes may help to clarify pivotal aspects in the diagnosis, prognosis, and therapies of IPF. PMID- 26893574 TI - The role of lasers and intense pulsed light technology in dermatology. AB - The role of light-based technologies in dermatology has expanded dramatically in recent years. Lasers and intense pulsed light have been used to safely and effectively treat a diverse array of cutaneous conditions, including vascular and pigmented lesions, tattoos, scars, and undesired hair, while also providing extensive therapeutic options for cosmetic rejuvenation and other dermatologic conditions. Dermatologic laser procedures are becoming increasingly popular worldwide, and demand for them has fueled new innovations and clinical applications. These systems continue to evolve and provide enhanced therapeutic outcomes with improved safety profiles. This review highlights the important roles and varied clinical applications that lasers and intense pulsed light play in the dermatologic practice. PMID- 26893578 TI - Strategies to promote adherence to nutritional advice in patients with chronic kidney disease: a narrative review and commentary. AB - Chronic kidney disease (CKD) requires extensive changes to food and lifestyle. Poor adherence to diet, medications, and treatments has been estimated to vary between 20% and 70%, which in turn can contribute to increased mortality and morbidity. Delivering effective nutritional advice in patients with CKD coordinates multiple diet components including calories, protein, sodium, potassium, calcium, phosphorus, and fluid. Dietary intake studies have shown difficulty in adhering to the scope and complexity of the CKD diet parameters. No single educational or clinical strategy has been shown to be consistently effective across CKD populations. Highest adherence has been observed when both diet and education efforts are individualized to each patient and adapted over time to changing lifestyle and CKD variables. This narrative review and commentary summarizes nutrition education literature and published strategies for providing nutritional advice in CKD. A cohort of practical and effective strategies for increasing dietary adherence to nutritional advice are provided that include communicating with "talking control" principles, integrating patient owned technology, acknowledging the typical food pattern may be snacking rather than formal meals, focusing on a single goal rather than multiple goals, creating active learning and coping strategies (frozen sandwiches, visual hands-on activities, planting herb gardens), and involving the total patient food environment. PMID- 26893577 TI - Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide. AB - Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro((r)), PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In conclusion, the overall benefit risk balance of sucroferric oxyhydroxide is deemed to be positive, and this new drug may therefore represent a good alternative to traditional phosphate binders for the treatment of hyperphosphatemia in dialysis patients. PMID- 26893580 TI - Interleukin-6 is a potential therapeutic target in interleukin-6 dependent, estrogen receptor-alpha-positive breast cancer. AB - INTRODUCTION: Interleukin-6 (IL-6) is an important growth factor for estrogen receptor-alpha (ERalpha)-positive breast cancer, and elevated serum IL-6 is associated with poor prognosis. METHODS: The role of the phosphorylated signal transducer and activator of transcription 3 pathway was investigated in ERalpha positive breast cancer. A panel of cell lines was treated with exogenous IL-6. An IL-6 specific gene signature was generated by profiling ten ERalpha-positive breast cancer cell lines alone or following treatment with 10 ng/mL recombinant IL-6 or human marrow stromal cell-conditioned media, with or without siltuximab (a neutralizing anti-IL-6 antibody) and grown in three-dimensional tumor microenvironment-aligned cultures for 4 days, 5 days, or 6 days. The established IL-6 signature was validated against 36 human ERalpha-positive breast tumor samples with matched serum. A comparative MCF-7 xenograft murine model was utilized to determine the role of IL-6 in estrogen-supplemented ERalpha-positive breast cancer to assess the efficacy of anti-IL-6 therapy in vivo. RESULTS: In eight of nine ERalpha-positive breast cancer cell lines, recombinant IL-6 increased phosphorylation of tyrosine 705 of STAT3. Differential gene expression analysis identified 17 genes that could be used to determine IL-6 pathway activation by combining their expression intensity into a pathway activation score. The gene signature included a variety of genes involved in immune cell function and migration, cell growth and apoptosis, and the tumor microenvironment. Validation of the IL-6 gene signature in 36 matched human serum and ERalpha-positive breast tumor samples showed that patients with a high IL-6 pathway activation score were also enriched for elevated serum IL-6 (>=10 pg/mL). When human IL-6 was provided in vivo, MCF-7 cells engrafted without the need for estrogen supplementation, and addition of estrogen to IL-6 did not further enhance engraftment. Subsequently, we prophylactically treated mice at MCF-7 engraftment with siltuximab, fulvestrant, or combination therapy. Siltuximab alone was able to blunt MCF-7 engraftment. Similarly, siltuximab alone induced regressions in 90% (9/10) of tumors, which were established in the presence which were established in the presence of hMSC expressing human IL-6 and estrogen. CONCLUSION: Given the established role for IL-6 in ERalpha-positive breast cancer, these data demonstrate the potential for anti-IL-6 therapeutics in breast cancer. PMID- 26893581 TI - EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10). AB - PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC. PMID- 26893582 TI - Benefit-risk assessment of golimumab in the treatment of refractory ulcerative colitis. AB - Significant advances in the management of patients with ulcerative colitis (UC) have been made since the introduction of anti-tumor necrosis factor (TNF)-alpha agents, especially for those who fail or do not tolerate conventional therapies. Two drugs, infliximab first, then adalimumab afterward, showed effectiveness in inducing and maintaining long-term remission both in pivotal trials as well as in clinical practice. However, approximately 25% of patients with UC, who fail or do not tolerate all available therapies, require a colectomy for refractory disease. The therapeutic scenario of UC has been recently upgraded by the introduction of golimumab, the latest anti TNF-alpha agent to be approved. Golimumab is a totally humanized monoclonal antibody, administered by a subcutaneous injection every 4 weeks. Treatment with golimumab has shown to be effective to induce sustained clinical benefit in tough-to-treat patients with UC, including steroid and/or immunosuppressive refractory and steroid-dependent patients. In this review, we summarize all available efficacy and safety data of golimumab in UC, analyzing the potential therapeutic position for the treatment of refractory patients with UC. PMID- 26893579 TI - Present-day challenges and future solutions in postoperative pain management: results from PainForum 2014. AB - This paper is a summary of presentations on postoperative pain control by the authors at the 2014 PainForum meeting in People's Republic of China. Postoperative pain is often untreated or undertreated and may lead to subsequent chronic pain syndromes. As more procedures migrate to the outpatient setting, postoperative pain control will become increasingly more challenging. Evidence based guidelines for postoperative pain control recommend pain assessment using validated tools on a consistent basis. In this regard, consistency may be more important than the specific tool selected. Many hospitals have introduced a multidisciplinary acute pain service (APS), which has been associated with improved patient satisfaction and fewer adverse events. Patient education is an important component of postoperative pain control, which may be most effective when clinicians chose a multimodal approach, such as paracetamol (acetaminophen) and opioids. Opioids are a mainstay of postoperative pain control but require careful monitoring and management of side effects, such as nausea, vomiting, dizziness, and somnolence. Opioids may be administered using patient-controlled analgesia systems. Protocols for postoperative pain control can be very helpful to establish benchmarks for pain management and assure that clinicians adhere to evidence-based standards. The future of postoperative pain control around the world will likely involve more and better established APSs and greater communication between patients and clinicians about postoperative pain. The changes necessary to implement and move forward with APSs is not a single step but rather one of continuous improvement and ongoing change. PMID- 26893576 TI - Non-invasive prenatal testing for fetal chromosome abnormalities: review of clinical and ethical issues. AB - Genomics-based non-invasive prenatal screening using cell-free DNA (cfDNA screening) was proposed to reduce the number of invasive procedures in current prenatal diagnosis for fetal aneuploidies. We review here the clinical and ethical issues of cfDNA screening. To date, it is not clear how cfDNA screening is going to impact the performances of clinical prenatal diagnosis and how it could be incorporated in real life. The direct marketing to users may have facilitated the early introduction of cfDNA screening into clinical practice despite limited evidence-based independent research data supporting this rapid shift. There is a need to address the most important ethical, legal, and social issues before its implementation in a mass setting. Its introduction might worsen current tendencies to neglect the reproductive autonomy of pregnant women. PMID- 26893584 TI - Mapping of Multiple Sclerosis Walking Scale (MSWS-12) to five-dimension EuroQol (EQ-5D) health outcomes: an independent validation in a randomized control cohort. AB - BACKGROUND: Mapping of patient-reported outcomes to the five-dimension EuroQol (EQ-5D) health index is increasingly being used for understanding the relationship of outcomes to health states and for predicting utilities that have application in economic evaluations. The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome that assesses the impact of walking impairment in people with MS. An equation for mapping the MSWS-12 to the EQ-5D was previously developed and validated using a North American Research Committee on MS (NARCOMS) registry cohort. MATERIALS AND METHODS: This analysis retested the validity of the equation mapping the MSWS-12 to the three-level EQ-5D (EQ-5D 3L) by using an independent cohort of patients with MS enrolled in a randomized controlled trial. Mapping was evaluated at two separate time points (baseline and week 4) during the clinical trial. The mapping equation's performance was subsequently assessed with mean absolute error (MAE) and root-mean-square error (RMSE) by comparing equation-based estimates to values elicited in the trial using the actual EQ-5D-3L questionnaire. RESULTS: The mapping equation predicted EQ-5D-3L values in this external cohort with reasonable precision at both time points (MAE 0.116 and RMSE 0.155 at baseline; MAE 0.105 and RMSE 0.138 at week 4), and was similar to that reported in the original NARCOMS cohort (MAE 0.109 and RMSE 0.145). Also as observed in the original NARCOMS cohort, the mapping equation performed best in patients with EQ-5D-3L values between 0.50 and 0.75, and poorly in patients with values <0.50. CONCLUSION: The mapping equation performed similarly in this external cohort as in the original derivation cohort, including a poorer performance in MS patients with more severe health-state severity. PMID- 26893583 TI - Rheumatoid polyarthritis suspected in an HIV patient with scleritis, peripheral ulcerative keratitis, and anterior uveitis. AB - INTRODUCTION: Scleritis and peripheral ulcerative keratitis are ocular manifestations found in many inflammations and infections. Therefore, their association should prompt a search for inflammatory or infectious causes that may be life-threatening, especially in the context of AIDS due to HIV infection. FINDINGS: We report the case of a 37-year-old female, first seen in 2011 with a nodular scleritis in the right eye and a peripheral ulcerative keratitis, a necrotizing scleritis, and a granulomatous anterior uveitis in the left eye, in the context of chronic polyarthropathies that had evolved over 6 months. The patient was diagnosed with AIDS (HIV) in 2008 and was on antiretroviral therapy for the past 2 years. Ophthalmic workup was negative for opportunistic infections and potential causes of scleritis and peripheral ulcerative keratitis, and the patient was unresponsive to topical antibacterial and anti-inflammatory treatment. Ocular lesion resolution and articular swelling improvement was observed less than 6 weeks after sulfasalazine treatment. Based on American College of Rheumatology/European League Against Rheumatism classification criteria, and considering the good response to the treatment (sulfasalazine), diagnosis of rheumatoid arthritis was made in the absence of confirmatory lab tests results. CONCLUSION: In the context of ocular manifestations associated with polyarthropathies, coexisting pathologies should be considered. Diagnostic workup of chronic inflammatory rheumatism should be carried out, even in the context of HIV/AIDS. PMID- 26893585 TI - Impact and feasibility of the Allied Health Professional Enhancement Program placements - experiences from rural and remote Queensland. AB - BACKGROUND: Allied health professionals practicing in rural and remote areas are often faced with barriers that prevent them from accessing professional development opportunities. In order to address this barrier, a tailored professional development program was developed and implemented by the Cunningham Centre in Queensland, Australia. The purpose of this study was to investigate the benefits of the program to participants and their work units. METHODS: This study used a concurrent mixed methods longitudinal design to investigate the medium- to long-term benefits of one Allied Health Professional Enhancement Program placement. Surveys and individual interviews provided data at 2 weeks and at 6 months post-placement. The study participants included the placement participant (a physiotherapist), their line manager, clinical supervisor, and the placement facilitator. RESULTS: Results demonstrated that the placement resulted in various reported benefits to the placement participant, as well as to service delivery in their home location. Benefits of the placement reported by the participant included increased confidence, improved knowledge and skills, increased access to professional networks, and validation of practice. Benefits to service delivery reported included improved efficiencies, improved patient outcomes, and positive impact on other team members. DISCUSSION: This study found that the Allied Health Professional Enhancement Program placement investigated was beneficial to the participant and to service delivery. In addition, the benefits reported were sustained at 6 months post-placement. Despite the fact that this study showcases experiences from one setting, the findings from this study and the lessons learnt may be transferrable to other similar programs elsewhere due to its methodological strengths (such as rich descriptions of the program and use of typical case sampling). While this study provides emergent evidence of usefulness of the program to participants and their work units, further studies are warranted to investigate the direct benefits of such placements on patient care, which remains as the holy grail of the impact of professional development opportunities. CONCLUSION: Allied Health Professional Enhancement Program placements can result in important benefits to the participant, their health service, and positively influence health care service delivery. PMID- 26893586 TI - Technology-enhanced learning should be employed alongside - not instead of - bedside teaching. PMID- 26893587 TI - Age patterns of racial/ethnic/nativity differences in disability and physical functioning in the United States. AB - BACKGROUND: Rapid population aging and increasing racial/ethnic and immigrant/native diversity make a broad documentation of U.S. health patterns during both mid- and late life particularly important. OBJECTIVE: We aim to better understand age- and gender-specific racial/ethnic and nativity differences in physical functioning and disability among adults aged 50 and above. METHODS: We aggregate 14 years of data from the National Health Interview Survey and calculate age- and gender-specific proportions of physical functioning and two types of disability for each population subgroup. RESULTS: Middle-aged foreign born individuals in nearly every subgroup exhibit lower proportions of functional limitations and disability than U.S.-born whites. This pattern of immigrant advantage is generally reversed in later life. Moreover, most U.S.-born minority groups have significantly higher levels of functional limitations and disability than U.S.-born whites in both mid- and late life. CONCLUSIONS: Higher levels of functional limitations and disability among U.S.-born minority groups and immigrant populations in older adulthood pose serious challenges for health providers and policymakers in a rapidly diversifying and aging population. PMID- 26893589 TI - Thai nurse cohort study: cohort profiles and key findings. AB - BACKGROUND: Globally, the nursing profession faces shortages, high turnover, and inequitable distribution. These problems are particularly acute in South East Asia. The present paper describes the design and initial findings of the Thai Nurse Cohort Study (TNCS). METHODS: The TNCS is a longitudinal prospective cohort study comprising multiple age cohorts, initiated in 2009 and expected to run until 2027. Cohorts comprise registered nurses (RN) holding professional licenses granted by the Thailand Nursing and Midwifery Council. Follow-up is at 3-year intervals, with new (younger) TNCS cohorts introduced and older, no-longer eligible members checked out. This maintains the cohort size as representative of the Thai RN population. The first survey round (2009) used a self-administered mailed questionnaire. The second round (2012) provided follow-up of the initial cohort and formed the baseline survey of new entries. RESULTS: The sampling frame for the first round was 142,699 licensed RN; 50,200 age-stratified participants were randomly selected and mailed the questionnaire, and 18,198 questionnaires were returned owing to incorrect addresses. Of the remaining 32,002 participants, 18,756 (58.6 %) responded (average age 43.7 +/- 9.8 years). About 15.4 % (equivalent to 20,000 of the current RN population), reported an intention to leave their nursing career. The second round achieved a follow-up rate of 60.2 %. This round included 3020 participants randomly selected from 6402 new RN (response rate, 38.3 %; mean age 23.1 +/- 3.5 years). In this round, 11.2 % reported they intended to leave nursing in the next 2 years. CONCLUSIONS: These two survey rounds have highlighted that Thailand is facing critical nurse shortages. A high rate of nurses expressed an intention to leave the profession; the capacity to replace these potential losses is much lower. PMID- 26893592 TI - The economic burden of childhood pneumococcal diseases in The Gambia. AB - BACKGROUND: Streptococcus pneumoniae is a common cause of child death. However, the economic burden of pneumococcal disease in low-income countries is poorly described. We aimed to estimate from a societal perspective, the costs incurred by health providers and families of children with pneumococcal diseases. METHODS: We recruited children less than 5 years of age with outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and bacterial meningitis at facilities in rural and urban Gambia. We collected provider costs, out of pocket costs and productivity loss for the families of children. For each disease diagnostic category, costs were collected before, during, and for 1 week after discharge from hospital or outpatient visit. RESULTS: A total of 340 children were enrolled; 100 outpatient pneumonia, 175 inpatient pneumonia 36 pneumococcal sepsis, and 29 bacterial meningitis cases. The mean provider costs per patient for treating outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and meningitis were US$8, US$64, US$87 and US$124 respectively and the mean out of pocket costs per patient were US$6, US$31, US$44 and US$34 respectively. The economic burden of outpatient pneumonia, inpatient pneumonia, pneumococcal sepsis and meningitis increased to US$15, US$109, US$144 and US$170 respectively when family members' time loss from work was taken into account. CONCLUSION: The economic burden of pneumococcal disease in The Gambia is substantial, costs to families was approximately one-third to a half of the provider costs, and accounted for up to 30 % of total societal costs. The introduction of pneumococcal conjugate vaccine has the potential to significantly reduce this economic burden in this society. PMID- 26893591 TI - Quality of life in patients with food allergy. AB - Food allergy has increased in developed countries and can have a dramatic effect on quality of life, so as to provoke fatal reactions. We aimed to outline the socioeconomic impact that food allergy exerts in this kind of patients by performing a complete review of the literature and also describing the factors that may influence, to a greater extent, the quality of life of patients with food allergy and analyzing the different questionnaires available. Hitherto, strict avoidance of the culprit food(s) and use of emergency medications are the pillars to manage this condition. Promising approaches such as specific oral or epicutaneous immunotherapy and the use of monoclonal antibodies are progressively being investigated worldwide. However, even that an increasing number of centers fulfill those approaches, they are not fully implemented enough in clinical practice. The mean annual cost of health care has been estimated in international dollars (I$) 2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95 % confidence interval I$324-I$1530). A similar result was found for adults in each country, and for children, and interestingly, it was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. The constant threat of exposure, need for vigilance and expectation of outcome can have a tremendous impact on quality of life. Several studies have analyzed the impact of food allergy on health-related quality of life (HRQL) in adults and children in different countries. There have been described different factors that could modify HRQL in food allergic patients, the most important of them are perceived disease severity, age of the patient, peanut or soy allergy, country of origin and having allergy to two or more foods. Over the last few years, several different specific Quality of Life questionnaires for food allergic patients have been developed and translated to different languages and cultures. It is important to perform lingual and cultural translations of existent questionnaires in order to ensure its suitability in a specific region or country with its own socioeconomic reality and culture. Tools aimed at assessing the impact of food allergy on HRQL should be always part of the diagnostic work up, in order to provide a complete basal assessment, to highlight target of intervention as well as to evaluate the effectiveness of interventions designed to cure food allergy. HRQL may be the only meaningful outcome measure available for food allergy measuring this continuous burden. PMID- 26893595 TI - Effects of heat-treatment on the stability and composition of metabolomic extracts from the earthworm Eisenia fetida. AB - Environmental metabolomics studies employing earthworms as sentinels for soil contamination are numerous, but the instability of the metabolite extracts from these organisms has been minimally addressed. This study evaluated the efficacy of adding a heat-treatment step in two commonly used extraction protocols (Bligh and Dyer and D2O phosphate buffer) as a pre-analytical stabilization method. The resulting metabolic profiles of Eisenia fetida were assessed using principal component analysis and NMR spectral evaluations. The heated Bligh and Dyer extractions produced stabilized profiles with minimal variation of the extracted metabolomic profiles over time, providing a more suitable method for metabolomic analysis of earthworm extracts. PMID- 26893594 TI - Steroidal saponins from the genus Allium. AB - Steroidal saponins are widely distributed among monocots, including the Amaryllidaceae family to which the Allium genus is currently classified. Apart from sulfur compounds, these are important biologically active molecules that are considered to be responsible for the observed activity of Allium species, including antifungal, cytotoxic, enzyme-inhibitory, and other. In this paper, literature data concerning chemistry and biological activity of steroidal saponins from the Allium genus has been reviewed. PMID- 26893596 TI - Bayesian module identification from multiple noisy networks. AB - BACKGROUND AND MOTIVATIONS: Module identification has been studied extensively in order to gain deeper understanding of complex systems, such as social networks as well as biological networks. Modules are often defined as groups of vertices in these networks that are topologically cohesive with similar interaction patterns with the rest of the vertices. Most of the existing module identification algorithms assume that the given networks are faithfully measured without errors. However, in many real-world applications, for example, when analyzing protein protein interaction networks from high-throughput profiling techniques, there is significant noise with both false positive and missing links between vertices. In this paper, we propose a new model for more robust module identification by taking advantage of multiple observed networks with significant noise so that signals in multiple networks can be strengthened and help improve the solution quality by combining information from various sources. METHODS: We adopt a hierarchical Bayesian model to integrate multiple noisy snapshots that capture the underlying modular structure of the networks under study. By introducing a latent root assignment matrix and its relations to instantaneous module assignments in all the observed networks to capture the underlying modular structure and combine information across multiple networks, an efficient variational Bayes algorithm can be derived to accurately and robustly identify the underlying modules from multiple noisy networks. RESULTS: Experiments on synthetic and protein-protein interaction data sets show that our proposed model enhances both the accuracy and resolution in detecting cohesive modules, and it is less vulnerable to noise in the observed data. In addition, it shows higher power in predicting missing edges compared to individual-network methods. PMID- 26893598 TI - Impaired angiogenesis in the enalapril-treated neonatal rat kidney. AB - PURPOSE: Nephrogenesis is normally accompanied by a tightly regulated and efficient vascularization. We investigated the effect of angiotensin II inhibition on angiogenesis in the developing rat kidney. METHODS: Newborn rat pups were treated with enalapril (30 mg/kg/day) or vehicle (control) for 7 days after birth. Renal histological changes were checked using Hematoxylin & Eosin staining. We also investigated the intrarenal expression of vascular endothelial growth factor (VEGF)-A, VEGF receptor 1 (VEGFR1), VEGFR2, platelet-derived growth factor (PDGF)-B, and PDGF receptor-beta with Western blotting and immunohistochemical staining at postnatal day 8. Expression of the endothelial cell marker CD31 was examined to determine glomerular and peritubular capillary density. RESULTS: Enalapril-treated rat kidneys showed disrupted tubules and vessels when compared with the control rat kidneys. In the enalapril-treated group, intrarenal VEGF-A protein expression was significantly higher, whereas VEGFR1 protein expression was lower than that in the control group (P<0.05). The expression of VEGFR2, PDGF-B, and PDGF receptor-beta was not different between the 2 groups. The increased capillary CD31 expression on the western blots of enalapril-treated rat kidneys indicated that the total endothelial cell protein level was increased, while the cortical capillary density, assessed using CD31 immunohistochemical staining, was decreased. CONCLUSION: Impaired VEGF-VEGFR signaling and altered capillary repair may play a role in the deterioration of the kidney vasculature after blocking of angiotensin II during renal development. PMID- 26893597 TI - Catch-up growth and catch-up fat in children born small for gestational age. AB - Infants born small for gestational age (SGA) are at increased risk of perinatal morbidity, persistent short stature, and metabolic alterations in later life. Recent studies have focused on the association between birth weight (BW) and later body composition. Some reports suggest that fetal nutrition, as reflected by BW, may have an inverse programing effect on abdominal adiposity later in life. This inverse association between BW and abdominal adiposity in adults may contribute to insulin resistance. Rapid weight gain during infancy in SGA children seemed to be associated with increased fat mass rather than lean mass. Early catch-up growth after SGA birth rather than SGA itself has been noted as a cardiovascular risk factor in later life. Children who are born SGA also have a predisposition to accumulation of fat mass, particularly intra-abdominal fat. It is not yet clear whether this predisposition is due to low BW itself, rapid postnatal catch-up growth, or a combination of both. In this report, we review the published literature on central fat accumulation and metabolic consequences of being SGA, as well as the currently popular research area of SGA, including growth aspects. PMID- 26893599 TI - Identification of 1p36 deletion syndrome in patients with facial dysmorphism and developmental delay. AB - PURPOSE: The 1p36 deletion syndrome is a microdeletion syndrome characterized by developmental delays/intellectual disability, craniofacial dysmorphism, and other congenital anomalies. To date, many cases of this syndrome have been reported worldwide. However, cases with this syndrome have not been reported in Korean populations anywhere. This study was performed to report the clinical and molecular characteristics of five Korean patients with the 1p36 deletion syndrome. METHODS: The clinical characteristics of the 5 patients were reviewed. Karyotyping and multiplex ligation-dependent probe amplification (MLPA) analyses were performed for genetic diagnoses. RESULTS: All 5 patients had typical dysmorphic features including frontal bossing, flat right parietal bone, low-set ears, straight eyebrows, down-slanting palpebral fissure, hypotelorism, flat nasal roots, midface hypoplasia, pointed chins, small lips, and variable degrees of developmental delay. Each patient had multiple and variable anomalies such as a congenital heart defect including ventricular septal defect, atrial septal defect, and patent duct arteriosus, ventriculomegaly, cryptorchism, or hearing loss. Karyotyping revealed the 1p36 deletion in only 1 patient, although it was confirmed in all 5 patients by MLPA analyses. CONCLUSION: All the patients had the typical features of 1p36 deletion. These hallmarks can be used to identify other patients with this condition in their early years in order to provide more appropriate care. PMID- 26893600 TI - Factors associated with mumps meningitis and the possible impact of vaccination. AB - PURPOSE: Mumps meningitis is a common complication of mumps infection; however, information on mumps meningitis in the postvaccine era is limited. The purpose of the present study was to determine factors associated with mumps meningitis and to discuss the effect of vaccination on this disease. METHODS: We retrospectively reviewed patients younger than 19 years with mumps, diagnosed at a university hospital in Korea between 2003 and 2013. Patients were divided into groups with and without meningitis, and the clinical features of the 2 groups were compared. RESULTS: The study enrolled 119 patients: 19 patients with meningitis and 100 patients without. Univariate analysis showed that older age (median: 15 years vs. 9.5 years, respectively), a longer interval from last vaccination (median: 10.2 years vs. 4.8 years, respectively), and febrile presentation (94.7% vs. 31.0%, respectively) were significantly associated with mumps meningitis. Sex, number of vaccination doses, bilateral parotitis, and the presence of complications other than meningitis did not differ between the 2 groups. In multivariate logistic regression analysis, age (odds ratio, 1.38; 95% confidence interval, 1.01-1.89; P=0.04) and fever (odds ratio, 30.46; 95% confidence interval, 3.27-283.61; P<0.01) remained independent factors for mumps meningitis. CONCLUSION: Clinicians in the postvaccine era should be aware of the possibility of mumps meningitis in febrile cases of mumps in adolescents, regardless of the number of vaccination doses. To establish the role of vaccination in mumps meningitis, further studies will be necessary. PMID- 26893601 TI - Clinical features of Bednar's aphthae in infants. AB - PURPOSE: Although Bednar's aphthae are common and regress spontaneously, these lesions may lead to feeding intolerance and are often misdiagnosed, rendering examinations useless. This study sheds new light on the clinical features of Bednar's aphthae. METHODS: Sixteen neonates and infants were newly diagnosed with Bednar's aphthae via routine health check-ups in an outpatient clinic. Medical records were retrospectively reviewed, and the following parameters were analyzed; sex, gestational age, birth weight, mode of delivery, and perinatal problems. A physical examination was carried out during the next outpatient visit to examine the healing process and check for the existence of scars or complications. RESULTS: Initial presentation included changes in feeding habits (n=10), longer feeding time, reduced intake, and increased irritability. In 6 patients, Bednar's aphthae were discovered incidentally, without prior symptoms. Feeding posture and method of feeding are important causes of Bednar's aphthae. Eleven patients were fed in a horizontal position, whereas 5 patients were fed in a semiseated position. Fifteen patients were bottle-fed, whereas 1 patient was exclusively breastfed. After correcting the feeding position, the ulcerative lesions disappeared within 1 month of diagnosis. During the follow-up period, lesions did not recur in any of the patients. CONCLUSION: This study suggests that Bednar's aphthae are caused by mechanical pressure. A diagnosis of Bednar's aphthae should be considered when lesions are found on the palate of infants and when symptoms seem to be feeding related. Proper education of parents can both treat Bednar's aphthae and easily prevent its recurrence. PMID- 26893602 TI - Intravenous levetiracetam versus phenobarbital in children with status epilepticus or acute repetitive seizures. AB - PURPOSE: This study compared the efficacy and tolerability of intravenous (i.v.) phenobarbital (PHB) and i.v. levetiracetam (LEV) in children with status epilepticus (SE) or acute repetitive seizure (ARS). METHODS: The medical records of children (age range, 1 month to 15 years) treated with i.v. PHB or LEV for SE or ARS at our single tertiary center were retrospectively reviewed. Seizure termination was defined as seizure cessation within 30 minutes of infusion completion and no recurrence within 24 hours. Information on the demographic variables, electroencephalography and magnetic resonance imaging findings, previous antiepileptic medications, and adverse events after drug infusion was obtained. RESULTS: The records of 88 patients with SE or ARS (median age, 18 months; 50 treated with PHB and 38 with LEV) were reviewed. The median initial dose of i.v. PHB was 20 mg/kg (range, 10-20 mg/kg) and that of i.v. LEV was 30 mg/kg (range, 20-30 mg/kg). Seizure termination occurred in 57.9% of patients treated with i.v. LEV (22 of 38) and 74.0% treated with i.v. PHB (37 of 50) (P=0.111). The factor associated with seizure termination was the type of event (SE vs. ARS) in each group. Adverse effects were reported in 13.2% of patients treated with i.v. LEV (5 of 38; n=4, aggressive behavior and n=1, vomiting), and 28.0% of patients treated with i.v. PHB (14 of 50). CONCLUSION: Intravenous LEV was efficacious and safe in children with ARS or SE. Further evaluation is needed to determine the most effective and best-tolerated loading dose of i.v. LEV. PMID- 26893603 TI - Early onset of colorectal cancer in a 13-year-old girl with Lynch syndrome. AB - Lynch syndrome is the most common inherited colon cancer syndrome. Patients with Lynch syndrome develop a range of cancers including colorectal cancer (CRC) and carry a mutation on one of the mismatched repair (MMR) genes. Although CRC usually occurs after the fourth decade in patients with Lynch syndrome harboring a heterozygous MMR gene mutation, it can occur in children with Lynch syndrome who have a compound heterozygous or homozygous MMR gene mutation. We report a case of CRC in a 13-year-old patient with Lynch syndrome and congenital heart disease. This patient had a heterozygous mutation in MLH1 (an MMR gene), but no compound MMR gene defects, and a K-RAS somatic mutation in the cancer cells. PMID- 26893604 TI - Tuberculosis-associated hemophagocytic lymphohistiocytosis in adolescent diagnosed by polymerase chain reaction. AB - We present a case of tuberculosis-associated hemophagocytic lymphohistiocytosis in a 14-year-old girl. The patient presented with weight loss, malaise, fatigue, prolonged fever, and generalized lymphadenopathy. Laboratory investigation revealed pancytopenia (white blood cells, 2,020 cells/uL; hemoglobin, 10.2 g/dL; platelets, 52,000 cells/uL), hypertriglyceridemia (229 mg/dL), and hyperferritinemia (1,420 ng/mL). Bone marrow biopsy showed a hypocellular bone marrow with a large numbers of histiocytes and marked hemophagocytosis; based on these findings, she was diagnosed with hemophagocytic lymphohistiocytosis. Polymerase chain reaction (PCR) with both the bone marrow aspiration and sputum samples revealed the presence of Mycobacterium tuberculosis. Antitubercular therapy with immune modulation therapy including dexamethasone and intravenous immunoglobulin was initiated. The results of all laboratory tests including bone marrow biopsy and PCR with both the bone marrow aspiration and sputum samples were normalized after treatment. Thus, early bone marrow biopsy and the use of techniques such as PCR can avoid delays in diagnosis and improve the survival rates of patients with tuberculosis-associated hemophagocytic lymphohistiocytosis. PMID- 26893605 TI - Acceptability and use of ready-to-use supplementary food compared to corn-soy blend as a targeted ration in an HIV program in rural Haiti: a qualitative study. AB - BACKGROUND: Ready-to-use supplementary food (RUSF) is increasingly used as a component of food rations for adults with HIV. METHODS: We undertook a qualitative study to evaluate the acceptability and use of peanut-based RUSF compared to corn-soy blend (CSB) among adults living with HIV in rural Haiti who had been enrolled in a prospective, randomized trial comparing the impact of those rations. A total of 13 focus groups were conducted with 84 participants-42 selected from the RUSF arm of the study, and 42 from the CSB arm-using a guide with pre-designated core topics and open-ended questions. RESULTS: We found that RUSF was highly acceptable in terms of taste, preparation, and packaging. Both types of food ration were widely shared inside and outside households, especially with children. However, while CSB was without exception stored with the communal household food supply, RUSF was frequently separated from the household food supply and was more often reserved for consumption by individuals with HIV. CONCLUSIONS: RUSF was a highly acceptable food ration that, compared to CSB, was more often reserved for use by the individual with HIV. Qualitative examination of the perceptions, use, and sharing of food rations is critical to understanding and improving the efficacy of food assistance for food-insecure people living with HIV. PMID- 26893606 TI - How to build your dragon: scaling of muscle architecture from the world's smallest to the world's largest monitor lizard. AB - BACKGROUND: The functional design of skeletal muscles is shaped by conflicting selective pressures between support and propulsion, which becomes even more important as animals get larger. If larger animals were geometrically scaled up versions of smaller animals, increases in body size would cause an increase in musculoskeletal stress, a result of the greater scaling of mass in comparison to area. In large animals these stresses would come dangerously close to points of failure. By examining the architecture of 22 hindlimb muscles in 27 individuals from 9 species of varanid lizards ranging from the tiny 7.6 g Varanus brevicauda to the giant 40 kg Varanus komodoensis, we present a comprehensive dataset on the scaling of musculoskeletal architecture in monitor lizards (varanids), providing information about the phylogenetic constraints and adaptations of locomotor muscles in sprawling tetrapods. RESULTS: Scaling results for muscle mass, pennation and physiological cross-sectional area (PCSA), all suggest that larger varanids increase the relative force-generating capacity of femur adductors, knee flexors and ankle plantarflexors, with scaling exponents greater than geometric similarity predicts. Thus varanids mitigate the size-related increases in stress by increasing muscle mass and PCSA rather than adopting a more upright posture with size as is shown in other animals. As well as the scaling effects of muscle properties with body mass, the variation in muscle architecture with changes in hindlimb posture were also prominent. Within varanids, posture varies with habitat preference. Climbing lizards display a sprawling posture while terrestrial lizards display a more upright posture. Sprawling species required larger PCSAs and muscle masses in femur retractors, knee flexors, and ankle plantarflexors in order to support the body. CONCLUSIONS: Both size and posture related muscle changes all suggest an increased role in support over propulsion, leading to a decrease in locomotor performance which has previously been shown with increases in size. These estimates suggest the giant Pleistocene varanid lizard (Varanus megalania priscus) would likely not have been able to outrun early humans with which it co-habitated the Australian landmass with. PMID- 26893609 TI - Erratum to: Consumers and their supporters' perspectives on poor practice and the use of seclusion and restraint in mental health settings: results from Australian focus groups. AB - [This corrects the article DOI: 10.1186/s13033-016-0038-x.]. PMID- 26893607 TI - Mental Health Literacy for Anxiety Disorders: How perceptions of symptom severity might relate to recognition of psychological distress. AB - PURPOSE: Improving mental health literacy is an important consideration when promoting expedient and effective treatment seeking for psychological disorders. Low recognition serves as a barrier to treatment (Coles and Coleman, 2010), and this article examines recognition by lay individuals of severity for three psychological disorders: social anxiety, generalized anxiety, and major depression using a dimensional approach. DESIGN: Vignettes of mild/subclinical, moderate, and severe cases of each disorder were rated for severity by a team of expert assessors and 270 participants (mean age = 26.8; 76.7% women). FINDINGS: Difference ratings were calculated comparing participants' responses to scores from the assessors. A within-groups factorial ANOVA with LSD follow-up was performed to examine the effects of Diagnosis and Severity on difference ratings. Both main effects [Diagnosis, F(2, 536)=35.26, Mse=1.24; Severity, F(2, 536)=9.44, Mse=1.93] and the interaction were significant [F(4, 1072)=13.70, Mse=1.13] all p's < 0.001. Social anxiety cases were underrated in the mild/subclinical and moderate cases, generalized anxiety cases were underrated at all three severities, and major depression cases were overrated at all three severities. SOCIAL IMPLICATIONS: Judgments of severity may underlie the low recognition rates for social anxiety disorder and generalized anxiety disorder. Future efforts should focus on improved recognition and education regarding anxiety disorders in the population, particularly before they become severe. VALUE: This project demonstrates the importance of considering judgments of symptom severity on a continuum, and in a range of cases, rather than just the ability to correctly label symptoms, when determining whether or not people recognize psychological disorders. PMID- 26893610 TI - Treating symptoms or assisting human development: Can different environmental conditions affect personal development for patients with severe mental illness? A qualitative study. AB - BACKGROUND: Recent research suggests that a basic anomaly in self-experience may be a core factor in patients with severe mental illnesses. Given the importance of sense of self, the traditional treatment of symptoms might not be the most effective for these groups of patients. This qualitative study examines how differences in social environmental conditions, organized as education or treatment, might affect personal development in patients with severe mental illness. METHODS: A qualitative hermeneutical design was used. Data were collected through qualitative interviews. Informants included 14 patients in psychiatric treatment and 15 students at schools for adults with mental illness. Most informants were interviewed on two occasions, 6-8 months apart, totaling 47 interviews. All participants had been diagnosed with severe mental illness with pronounced impact on daily functioning (most often psychoses or personality disorders) for a minimum of 2 years. RESULTS: Findings and interpretations showed that the students experienced a supportive environment focused mostly on education. They described personal and enduring development in areas such as capacity for relationships, regulation of symptoms, subjective well-being, and integration in society. The patients experienced an environment focused more on treatment of their illness and less on personal development and interests. They described little development, much loneliness, a poor quality of life, an objectifying attitude of themselves and others, and hopelessness. CONCLUSIONS: Even if more research is needed, findings indicate that for this group of patients, problems may be closely related to identity development. Therefore, instead of solemnly focusing on specific symptoms, it might be more effective to support patients' personal and social development by offering intensive and lasting social environmental conditions. This includes stable and mutual relationships, intrinsically motivated activities, and an environment that supports personal choices, acceptance, and development. PMID- 26893612 TI - Application of multicolor banding combined with heterochromatic and locus specific probes identify evolutionary conserved breakpoints in Hylobates pileatus. AB - BACKGROUND: The question what makes Homo sapiens sapiens (HSA) special among other species is one of the basic questions of mankind. A small contribution to answer this question is to study the chromosomal constitution of HSA compared to other, closely related species. In order to check the types and extent of evolutionary conserved breakpoints we studied here for the first time the chromosomes of Hylobates pileatus (HPI) compared to HSA and Hylobates lar (HLA) by means of molecular cytogenetics. RESULTS: Overall, 68 new evolutionary conserved breakpoints compared to HSA could be characterized in this study. Interestingly, only seven of those were different compared to HLA. However, application of heterochromatic human DNA-probes provided evidence that observed high chromosomal rearrangement rates of gibbons in HPI happened rather in these repetitive elements than in euchromatin, even though most centromeric positions were preserved in HPI compared to HSA. CONCLUSION: Understanding genomes of other species and comparing them to HSA needs full karyotypic and high resolution genomic data to approach both: euchromatic and heterochromatic regions of the studied chromosome-content. This study provides full karyotypic data and previously not available data on heterochromatin-syntenies of HPI and HSA. PMID- 26893611 TI - Anoxic metabolism and biochemical production in Pseudomonas putida F1 driven by a bioelectrochemical system. AB - BACKGROUND: Pseudomonas putida is a promising host for the bioproduction of chemicals, but its industrial applications are significantly limited by its obligate aerobic character. The aim of this paper is to empower the anoxic metabolism of wild-type Pseudomonas putida to enable bioproduction anaerobically, with the redox power from a bioelectrochemical system (BES). RESULTS: The obligate aerobe Pseudomonas putida F1 was able to survive and produce almost exclusively 2-Keto-gluconate from glucose under anoxic conditions due to redox balancing with electron mediators in a BES. 2-Keto-gluconate, a precursor for industrial anti-oxidant production, was produced at an overall carbon yield of over 90 % based on glucose. Seven different mediator compounds were tested, and only those with redox potential above 0.207 V (vs standard hydrogen electrode) showed interaction with the cells. The productivity increased with the increasing redox potential of the mediator, indicating this was a key factor affecting the anoxic production process. P. putida cells survived under anaerobic conditions, and limited biofilm formation could be observed on the anode's surface. Analysis of the intracellular pools of ATP, ADP and AMP showed that cells had an increased adenylate energy charge suggesting that cells were able to generate energy using the anode as terminal electron acceptor. The analysis of NAD(H) and NADP(H) showed that in the presence of specific extracellular electron acceptors, the NADP(H) pool was more oxidised, while the NAD(H) pool was unchanged. This implies a growth limitation under anaerobic conditions due to a shortage of NADPH and provides a way to limit biomass formation, while allowing cell maintenance and catalysis at high purity and yield. CONCLUSIONS: For the first time, this study proved the principle that a BES-driven bioconversion of glucose can be achieved for a wild-type obligate aerobe. This non-growth bioconversion was in high yields, high purity and also could deliver the necessary metabolic energy for cell maintenance. By combining this approach with metabolic engineering strategies, this could prove to be a powerful new way to produce bio-chemicals and fuels from renewables in both high yield and high purity. PMID- 26893613 TI - Ring chromosome 18 in combination with 18q12.1 (DTNA) interstitial microdeletion in a patient with multiple congenital defects. AB - BACKGROUND: Ring chromosome 18 [r(18)] syndrome represents a relatively rare condition with a complex clinical picture including multiple congenital dysmorphia and varying degrees of mental retardation. The condition is cytogenetically characterized by a complete or mosaic form of ring chromosome 18, with ring formation being usually accompanied by the partial loss of both chromosomal arms. Here we observed a 20-year-old male patient who along with the features typical for r(18) carriers additionally manifested a severe congenital subaortic stenosis. To define the genetic basis of such a compound phenotype, standard cytogenetic and high-resolution molecular-cytogenetic analysis of the patient was performed. CASE PRESENTATION: Standard chromosome analysis of cultured lymphocytes confirmed 46, XY, r(18) karyotype. Array-based comparative genomic hybridization (array-CGH) allowed to define precisely the breakpoints of 18p and 18q terminal deletions, thus identifying the hemizygosity extent, and to reveal an additional duplication adjoining the breakpoint of the 18p deletion. Apart from the terminal imbalances, we found an interstitial microdeletion of 442 kb in size (18q12.1) that encompassed DTNA gene encoding alpha-dystrobrevin, a member of dystrophin-associated glycoprotein complex. While limited data on the role of DTNA missense mutations in pathogenesis of human cardiac abnormalities exist, a microdeletion corresponding to whole DTNA sequence and not involving other genes has not been earlier described. CONCLUSIONS: A detailed molecular cytogenetic characterization of the patient with multiple congenital abnormalities enabled to unravel a combination of genetic defects, namely, a ring chromosome 18 with terminal imbalances and DTNA whole-gene deletion. We suggest that such combination could contribute to the complex phenotype. The findings obtained allow to extend the knowledge of the role of DTNA haploinsufficiency in congenital heart malformation, though further comprehensive functional studies are required. PMID- 26893614 TI - Inhibition of Toxic IAPP Amyloid by Extracts of Common Fruits. AB - The aggregation of the 37-amino acid polypeptide islet amyloid polypeptide (IAPP, amylin), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic beta-islet cells in type 2 diabetes. It is believed that inhibiting the aggregation of IAPP may slow down, if not prevent entirely, the progression of this disease. Extracts of thirteen different common fruits were analyzed for their ability to prevent the aggregation of amyloidogenic IAPP. Thioflavin T binding, immuno-detection and circular dichroism assays were performed to test the in vitro inhibitory potential of each extract. Atomic force microscopy was used to visualize the formation of amyloid fibrils with and without each fruit extract. Finally, extracts were tested for their ability to protect living mammalian cells from the toxic effects of amyloid IAPP. Several fruits showed substantial ability to inhibit IAPP aggregation and protect living cells from toxic IAPP amyloid. PMID- 26893615 TI - Surface antigens contribute differently to the pathophysiological features in serotype K1 and K2 Klebsiella pneumoniae strains isolated from liver abscesses. AB - BACKGROUND: The virulence role of surface antigens in a single serotype of Klebsiella pneumoniae strain have been studied, but little is known about whether their contribution will vary with serotype. METHOD: To investigate the role of K and O antigen in hyper-virulent strains, we constructed O and K antigen deficient mutants from serotype K1 STL43 and K2 TSGH strains from patients with liver abscess, and characterized their virulence in according to the abscess formation and resistance to neutrophil phagocytosis, serum, and bacterial clearance in liver. RESULTS: Both of K1 and K2-antigen mutants lost their wildtype resistance to neutrophil phagocytosis and hepatic clearance, and failed to cause abscess formation. K2-antigen mutant became serum susceptible while K1-antigen mutant maintained its resistance to serum killing. The amount of glucuronic acid, indicating the amount of capsular polysaccharide (CPS, K antigen), was inversed proportional to the rate of phagocytosis. O-antigen mutant of serotype K1 strains had significantly more amount of CPS, and more resistant to neutrophil phagocytosis than its wildtype counterpart. O-antigen mutants of serotype K1 and K2 strains lost their wildtype serum resistance, and kept resistant to neutrophil phagocytosis. While both mutants lacked the same O1 antigen, O-antigen mutant of serotype K1 became susceptible to liver clearance and cause mild abscess formation, but its serotype K2 counterpart maintained these wildtype virulence. CONCLUSION: We conclude that the contribution of surface antigens to virulence of K. pneumoniae strains varies with serotypes. PMID- 26893616 TI - De Novo sphingolipid synthesis is essential for Salmonella-induced autophagy and human beta-defensin 2 expression in intestinal epithelial cells. AB - BACKGROUND: Sphingolipids are important for innate immune response to eliminate infected pathogens and involved in autophagy. On the other hand, nucleotide binding oligomerization domain-containing protein 2 (NOD2) served as an intracellular pattern recognition receptor to enhance host defense by inducing autophagy and the production of antimicrobial peptides, such as human beta defensin-2 (hBD-2). However, the role of sphingolipids in Salmonella-induced autophagy and hBD-2 response in intestinal epithelial cells has not been previously elucidated. METHODS: Salmonella typhimurium wild-type strain SL1344 was used to infect SW480, an intestinal epithelial cell. hBD-2 and interleukin-8 (IL-8) mRNA expressions were assessed in SW480 cells using RT-PCR, and intracellular signaling pathways and autophagy protein expression were analyzed by Western blot in SW480 cells in the presence or absence of inhibitors or transfected with siRNA. RESULTS: We demonstrated that inhibition of de novo sphingolipid synthesis repressed the membrane recruitment of NOD2 and autophagy related protein 16-like 1 (Atg16L1), suppressed Salmonella-induced autophagic protein LC3-II expression, and reduced NOD2-mediated hBD-2 response in Salmonella infected SW480 cells. Contrasting to the utilization of membrane cholesterol on maintenance of Salmonella-containing vacuoles and anti-inflammation by Salmonella, sphingolipids act on epithelial defense against the invasive pathogen. CONCLUSIONS: Our results offer mechanistic insights on the role of de novo sphingolipid synthesis in the innate immunity of intestinal epithelial cells to Salmonella infection. The pharmaceuticals enhancing or diet enriched with sphingolipids may induce the dual anti-bacterial mechanisms. The role of de novo sphingolipid synthesis on inflammatory bowel disease is deserved to be further investigated. PMID- 26893617 TI - The risk of metabolic syndrome after gestational diabetes mellitus - a hospital based cohort study. AB - BACKGROUND: Women with gestational diabetes mellitus (GDM) are at an increased risk of developing metabolic syndrome (MetS) after delivery. Recently, the prevalence of both GDM and MetS has increased worldwide, in parallel with obesity. We investigated whether the presentation of MetS and its clinical features among women with previous GDM differs from that among those with normal glucose tolerance during pregnancy, and whether excess body weight affects the results. METHODS: This hospital-based study of two cohorts was performed in Kanta Hame Central Hospital, Finland. 120 women with a history of GDM and 120 women with a history of normal glucose metabolism during pregnancy, all aged between 25 and 46 were enrolled. They all underwent physical examination and had baseline blood samples taken. All 240 women were also included in subgroup analyses to study the effect of excess body weight on the results. RESULTS: Although the groups did not differ in body mass index (BMI; p = 0.069), the risk of developing MetS after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 19 vs. 8 cases (p = 0.039). Fasting glucose (p < 0.001) and triglyceride levels (p < 0.001) were significantly higher in women affected. In subgroup analysis, cardiovascular risk factors were more common in participants with high BMI than in those with previous gestational diabetes. CONCLUSIONS: The risk of MetS was 2.4-fold higher after GDM than after normal pregnancy. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM. Multivariate analysis supported the main findings. Weight control is important in preventing MetS after delivery. PMID- 26893620 TI - PPARgamma activation reduces ischemia/reperfusion-induced metastasis in a murine model of hepatocellular carcinoma. AB - Ischemia/reperfusion (I/R) injury during liver resection or transplantation for the treatment of hepatocellular carcinoma (HCC) may increase the risk of metastasis. Peroxisome proliferator-activated receptor-gamma (PPARgamma) activation has been observed to exert a protective effect against hepatic I/R injury. However, whether PPARgamma activation exerts a protective effect against I/R-associated liver metastasis remains unknown. Therefore, the present study aimed to investigate the effects of the PPAR agonist rosiglitazone and the specific PPARgamma antagonist GW9662 on tumor metastasis following hepatic I/R. An experimental mouse model of hepatic I/R-induced HCC metastasis was designed in order to determine the effects of I/R on tumor metastasis in the liver. Four groups were established: Sham, control (I/R), rosiglitazone (Ro) and rosiglitazone with GW9662 (Ro + GW) groups. In the latter two groups, the treatments were administered intravenously 1 h prior to the induction of ischemia. Tumor load was measured 12 days after the procedure. Furthermore, tissue analyses were conducted to determine the expression levels of alanine aminotransferase, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-9, vascular cell adhesion molecule (VCAM)-1, nuclear factor (NF)-kappaB and PPARgamma. Rosiglitazone pretreatment appeared to significantly mitigate hepatic I/R injury, as indicated by serological and histological analysis. The levels of VCAM-1, MPO and MMP-9 expression in the Ro group were significantly reduced at 8 h following ischemia compared with those in the control and Ro + GW groups. In addition, rosiglitazone inhibited the I/R-induced activation of NF-kappaB, and GW9662 attenuated the inhibitory effect. To the best of our knowledge, the present study is the first to report on the expression and the functional roles of PPARgamma in I/R-associated metastasis. Short-term treatment of mice with rosiglitazone, a potent PPARgamma agonist, confers protective effects against hepatic I/R-associated metastasis. Thus, PPARgamma may be a potential therapeutic target for the protection of the liver against I/R-associated metastasis. PMID- 26893618 TI - Efficacy and safety of bevacizumab for the treatment of glioblastoma. AB - Glioblastoma (GBM) is the most common and devastating primary malignant intracranial tumor in adults. The current first-line treatment for patients with newly diagnosed GBM is surgical resection followed by radiotherapy plus concomitant and adjuvant temozolomide. This treatment protocol may prolong the survival period of the patient, however it is not curative and more effective therapeutic strategies are required. GBM is a type of highly vascularized tumor with increased expression levels of vascular endothelial growth factor (VEGF), which is a significant mediator of angiogenesis. Since angiogenesis is essential for tumor growth, anti-angiogenic therapies hold potential for the treatment of GBM, and targeting VEGF has demonstrated promising results in previous studies. Bevacizumab (BEV) is a recombinant humanized monoclonal antibody that inhibits VEGF and is approved by the US Food and Drug Administration as a monotherapy treatment for patients with recurrent GBM and is associated with manageable toxicity. Previous studies have demonstrated that BEV may be an effective treatment for recurrent GBM, with prolonged progression-free survival and overall survival, and maintained patient quality of life and functional status. The present review article briefly outlines the mechanism of action of BEV and summarizes the current literature and clinical trial research on the role of BEV for the treatment of patients with recurrent and newly diagnosed GBM. PMID- 26893619 TI - Clinical and radiographic observations from four patients with primary hepatic lymphoma. AB - The aim of the present study was to delineate the radiographic and clinical features of primary hepatic lymphoma (PHL). Four histopathologically confirmed cases of PHL were analyzed with respect to the radiological, clinical and pathological characteristics. The main clinical manifestations included upper right quadrant pain and lymphoma-associated B symptoms, such as fever, night sweating and weight loss. All the patients had elevated serum levels of lactate dehydrogenase. Furthermore, all the patients underwent plain and enhanced computed tomography examinations, which identified low-density lesions without marked enhancement. Solitary masses were observed in two cases, while multiple focal lesions were noted in one case and diffuse multi-speckled nodules were observed in one case. Two patients underwent abdominal magnetic resonance imaging, which revealed lesions that were hyperintense on T1-weighted imaging (WI) scans and hypointense on T2WI scans, and exhibited slight to moderate enhancement with a dynamic contrast-enhanced protocol. In one case, vessels were visible within the lesion. Therefore, the present study concluded that PHL is a rare condition that exhibits non-specific clinical and radiological features. A combination of imaging results and clinical manifestations can be used to facilitate a diagnosis of PHL. PMID- 26893621 TI - Effect of local insulin injection on wound vascularization in patients with diabetic foot ulcer. AB - The aim of the present study was to investigate the effect of local insulin injection on granulation tissue formation in the wounds of patients with diabetic foot ulcer. Thirty-two patients with diabetic foot ulcer were randomly divided into an insulin (n=18) and a control (n=14) group. In the diabetic foot ulcer wound, the insulin group were administered insulin and the control group were administered an equal volume of saline. Prior to injection and at 0.5, 1.0, 2.0 and 4.0 h after injection, the fingertip blood glucose levels were determined. The growth of granulation tissue was assessed continuously for 12 days. Wound tissue was harvested at 0, 5, 7 and 12 days for the detection of CD34 expression by immunohistochemistry. The microvessel density (MVD) was calculated. No significant difference in the fasting blood glucose level was found between the two groups at any time-point (P>0.05). Growth of granulation tissue in the insulin group was more marked from 7 days after local insulin injection (24.87+/ 0.24) and was significantly different from that in the control group (18.66+/ 0.45) (P<0.01). New vessels were observed in the insulin group 3 days after insulin injection; however, there was no significant difference in MVD compared with the control group (P>0.05). The MVD in the insulin group increased markedly from 5 days after treatment, and the difference between the two groups was significant (P<0.01). In conclusion, local injection of insulin into the base of a diabetic foot ulcer has a significant effect on systemic blood glucose and may promote wound healing by improving the growth of granulation tissue. PMID- 26893622 TI - Isobavachalcone induces the apoptosis of gastric cancer cells via inhibition of the Akt and Erk pathways. AB - In the present study, the MGC803 gastric cancer cell line was used as an experimental model to evaluate the potential role of isobavachalcone (IBC) in cell apoptosis, migration and invasion. The inhibitory effects of IBC on cell proliferation were determined using a methylthiazolyltetrazolium assay. Cellular morphological changes were assessed using Wright-Giemsa staining, and cell apoptosis was evaluated by flow cytometric analysis. The results of the present study demonstrated that IBC inhibited the proliferation of MGC803 cells in a concentration- and time-dependent manner. Furthermore, the wound healing and MatrigelTM Transwell(r) invasion assays demonstrated that IBC decreased cell migration and invasion in a concentration-dependent manner. Western blotting was used to determine the protein expression levels of caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), as well as the key protein kinases in the Akt and extracellular signal-regulated kinase (Erk) signaling pathways. During the IBC-induced apoptosis of MGC803 cells, transient activation of phosphorylated (p)-Akt and p-Erk inhibited the activation of Akt and Erk, upregulated Bax expression, downregulated Bcl-2 expression and activated caspase 3. These results suggest that IBC inhibited the growth of MGC803 gastric cancer cells by regulating the protein expression of caspase-3, Bcl-2 and Bax. In addition, inhibition of the Akt and Erk signaling pathways may be important mechanisms underlying the IBC-induced apoptosis of gastric cancer cells. PMID- 26893624 TI - Puerarin attenuates the inflammatory response and apoptosis in LPS-stimulated cardiomyocytes. AB - Patients with septic shock suffer from high mortality rates, particularly when complicated by severe myocardial depression which is characterized by hypotension and a reduction in cardiac output. Inflammation is an important factor involved in the early stages of sepsis. The aim of the present study was to investigate the effect of the Chinese herbal compound puerarin (1, 5, 10, 20 and 40 uM) on cardiomyocyte inflammatory response in a sepsis model using H9c2 cardiomyocytes stimulated with 1 ug/ml lipopolysaccharide (LPS). The mRNA expression levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-beta were evaluated using reverse transcription-quantitative polymerase chain reaction. In addition, the protein expression levels of various factors were determined using western blot analysis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was used to evaluate the apoptosis rates in the various groups, and immunocytochemical analysis was employed to determine the effect of puerarin on the nuclear translocation of p65 protein. The present study demonstrated that LPS stimulation increased IL-1beta and TNF-alpha mRNA expression levels, as compared with the controls (P<0.05). Following treatment with various concentrations of puerarin, the expression levels of IL-1beta and TNF-alpha were markedly blunted, particularly in the LPS + 40 uM puerarin group (P<0.05 vs. the LPS group). Furthermore, puerarin administration significantly inhibited LPS-induced apoptosis in H9c2 cardiomyocytes, as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining (TUNEL positive cells: LPS + 40 uM puerarin group, 5.5% vs. LPS group, 10.5%; P<0.01). In addition, puerarin significantly decreased LPS-induced phosphorylated nuclear factor (p-NF)-kappaB p65 and Bax expression levels, and increased the expression levels of Bcl-2, as compared with the LPS group (P<0.05). These data indicated that puerarin may serve as a valuable protective agent against cardiovascular inflammatory diseases. PMID- 26893625 TI - Increased expression of FERM domain-containing 4A protein is closely associated with the development of rectal cancer. AB - The aim of the present study was to detect the expression levels of FERM domain containing 4A (FRMD4A) in rectal cancer tissues and peripheral blood and to investigate the correlation between FRMD4A and cancer development. A total of 78 consecutive patients were enrolled in this study. Thirty healthy individuals were used as the control group. The expression of FRMD4A in rectal cancer and the corresponding normal adjacent tissues was detected by immunohistochemistry and western blotting. The expression of FRMD4A mRNA in peripheral blood was detected by reverse transcription-quantitative polymerase chain reaction. The expression of FRMD4A in rectal cancer tissues was found to be negatively correlated with the degree of differentiation, depth of invasion and Dukes' stage. A negative correlation was identified between FRMD4A and epithelial cadherin expression. The expression of FRMD4A in the peripheral blood of patients with rectal cancer was significantly increased compared with that in the control group (P<0.05). Expression of FRMD4A in the peripheral blood in the patients with lymph node metastasis was significantly increased compared with that in the patients without lymph node metastasis (P<0.05). These results indicate that the expression of FRMD4A is significantly increased in rectal cancer tissues and the peripheral blood of patients with rectal cancer, and the expression levels of FRMD4A are closely associated with differentiation, invasion of rectal cancer and Dukes' stage. In conclusion, the findings of the present study suggest that FRMD4A may be used as a target for the diagnosis and treatment of rectal cancer. PMID- 26893623 TI - Inhibitory effects of 90Sr/90Y beta-irradiation on alkali burn-induced corneal neovascularization in rats. AB - The aim of the present study was to investigate the inhibitory effects of 90Sr 90Y beta-irradiation in a rat model of alkali burn-induced corneal neovascularization (CNV). Alkali burn-induced CNV was induced in the right eyes of 30 female Wistar rats, which were randomly divided into the following three groups (n=10/group): i) The alkali burn control group, which received a balanced salt solution treatment; ii) group 1, which received treatment with angiogenesis inhibitors; and iii) group 2, which received 90Sr-90Y beta-irradiation treatment. A further 10 female Wistar rats comprised a blank control group and received only balanced salt solution. Digital photographs of the corneas were acquired and the area of NV was calculated. In addition, the expression levels of matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-1 and VEGFR-2 in alkali-burned rat corneas were determined using western blot analysis. The results suggested that the number of new vessels and the area of CNV were significantly decreased in groups 1 and 2, as compared with the alkali burn group at each time point (P<0.05). In addition, the number of inflammatory cells and the degree of edema were decreased in groups 1 and 2, as compared with the alkali burn group, with group 2 exhibiting the most marked reduction. Western blot analysis demonstrated that the expression levels of MMP 9, VEGF, VEGFR-1 and VEGFR-2 were significantly decreased in groups 1 and 2, as compared with the alkali burn control group, with group 2 exhibiting the most significant reduction (P<0.05). The results of the present study suggested that 90Sr-90Y beta-irradiation and angiogenesis inhibitor treatments were able to inhibit alkali burn-induced CNV, although 90Sr-90Y beta-irradiation may be more effective. PMID- 26893627 TI - Correlation studies of barium on pulmonary infection under the assessment of VFSS. AB - Stroke is a common clinical disease resulting in somatic dyskinesia as well as different degrees of dysphagia. The aim of the study was to assess the results obtained from the utilization of 60% barium sulfate suspension and iohexol as contrast agents in video fluoroscopic swallowing studies (VFSS), and compare the association between the clinical application of the two contrast agents and the incidence of pneumonia. A total of 60 cases of in-patients with dysphagia caused by stroke were selected and divided into two groups based on the diagnostic standard. No obvious differences were evident between the groups with regard to gender, age, position of stroke and the nature of stroke. The patients were divided into an iohexol group of 30 patients administered with 350 mgI/ml iohexol as a contrast agent, and a barium sulfate group of 30 patients administered with 60% barium sulfate suspension as a contrast agent. A VFSS evaluation was implemented before and after 3 weeks of treatment, respectively, and the pharynx transit time was compared between the two groups of contrast agents according to the position of stroke. By using case-control studies, the incidence of pneumonia between the two groups of patients within 2 weeks after hospitalization was analyzed and the association between the complication probability with different contrast agents was analyzed. After 2 weeks in hospital, the incidence of aspiration pneumonia of the two groups was statistically significant (P<0.05). The incidence of pneumonia of the iohexol group was markedly lower than that of the barium sulfate group, which may be important for barium aspiration. In conclusion, in the VFSS of dysphagia after stroke and barium sulfate increased the incidence of pneumonia, and that iohexol was widely used in video fluoroscopy. PMID- 26893626 TI - Hepatic injury is associated with cell cycle arrest and apoptosis with alteration of cyclin A and D1 in ammonium chloride-induced hyperammonemic rats. AB - Hyperammonemia is considered to be central to the pathophysiology of hepatic encephalopathy in patients exhibiting hepatic failure (HF). It has previously been determined that hyperammonemia is a serious metabolic disorder commonly observed in patients with HF. However, it is unclear whether hyperammonemia has a direct adverse effect on hepatic cells or serves as a cause and effect of HF. The present study investigated whether hepatic injury is caused by hyperammonemia, and aimed to provide an insight into the causes and mechanisms of HF. Hyperammonemic rats were established via intragastric administration of ammonium chloride solution. Hepatic tissues were assessed using biochemistry, histology, immunohistochemistry, flow cytometry (FCM), semi-quantitative reverse transcription-polymerase chain reaction and western blot analysis. Hyperammonemic rats exhibited significantly increased levels of liver function markers, including alanine transaminase (P<0.01), aspartate aminotransferase (P<0.01), blood ammonia (P<0.01) and direct bilirubin (P<0.05), which indicated hepatic injury. A pathological assessment revealed mild hydropic degeneration, but no necrosis or inflammatory cell infiltration. However, terminal deoxynucleotidyl transferase dUTP nick end-labeling assays confirmed a significant increase in the rate of cellular apoptosis in hyperammonemic rat livers (P<0.01). FCM analysis revealed that there were significantly more cells in the S phase and fewer in the G2/M phase (P<0.01), and the expression levels of cyclin A and D1 mRNA and proteins were significantly increased (P<0.01). In summary, cell cycle arrest, apoptosis and an alteration of cyclin A and D1 levels were all markers of hyperammonemia-induced hepatic injury. These findings provide an insight into the potential mechanisms underlying hyperammonemia-induced hepatic injury, and may be used as potential targets for treating or preventing hepatic damage caused by hyperammonemia, including hepatic encephalopathy. PMID- 26893628 TI - Biological characterization of metanephric mesenchymal stem cells from the Beijing duck. AB - Mesenchymal stem cells (MSCs) possess self-proliferation and multi-directional differentiation abilities. Previous studies on MSCs have mostly focused on the bone marrow, lungs, pancreas and umbilical cord blood, with few studies on metanephric tissues in ducks. For the present study, the Beijing duck was selected as an experimental animal. Duck embryo metanephric mesenchymal stem cells (MMSCs) were studied. MMSC isolation culture, analysis of biological characteristics, induced differentiation and identification were performed in preliminary experiments. In the current study, surface antigens and gene expression patterns were detected using immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. The induced cells, adipocytes, hepatocytes, epithelial cells and islet cells were identified by oil red O staining, periodic acid-Schiff staining, immunofluorescence and dithizone staining, respectively. RT-PCR was performed for detection of specific marker genes. The results suggested that the biological characteristics of MMSCs were similar to those of the MSCs previously analyzed. Primary MMSCs were sub-cultured to passage 21. The induced cells exhibit typical staining and immunofluorescence indicating the expression of specific genes. This demonstrates that MMSCs may be a novel alternative source of MSCs for experimental and clinical applications. PMID- 26893629 TI - Sevoflurane exerts a more marked influence compared with propofol on gene expression in patients undergoing coronary artery bypass graft surgery. AB - The aim of the present study was to elucidate the influence of the anesthetics propofol and sevoflurane on gene expression in patients undergoing coronary artery bypass graft surgery (CABG) and to provide a basis for the selection of the appropriate anesthetic. The gene expression profiles of patients receiving one of the two anesthetics were analyzed prior to and following the induction of anesthesia. GSE4386 microarray data obtained from the Gene Expression Omnibus database was used to identify the differentially expressed genes (DEGs) by significance analysis of the microarray. The data set contained data regarding atrial tissue samples from 40 patients that underwent CABG, and that received either propofol (n=10) or sevoflurane (n=10) or were control subjects (n=20). The 20 control samples comprised the same patients prior to undergoing CABG. The Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) Enrichment Analysis was applied to the DEGs using the Database for Annotation, Visualization and Integration Discovery functional annotation bioinformatics microarray tool. A total of 242 and 560 DEGs were identified in the human atrial samples treated with propofol and sevoflurane, respectively. Among these, 116 upregulated DEGs and no downregulated DEGs were found to be unique to sevoflurane, while 10 upregulated and 212 downregulated DEGs were unique to propofol. The majority of the pathways that were significantly over-represented among the upregulated DEGs were associated with the immune response, such as Toll- and NOD-like receptors and Jak-STAT signaling pathways. GO enrichment analysis revealed that the downregulated DEGs unique to sevoflurane treatment were involved in the immune response and glucose metabolism, while the upregulated DEGs were associated with cellular ion homeostasis and epithelial cell development. Compared with propofol, sevoflurane appeared to exert a more marked effect on biological pathways, such as drug metabolism, glycolysis, cellular ion homeostasis and epithelial cell development. PMID- 26893630 TI - Radiation-induced anaplastic ependymoma mimicking a skull base meningioma: A case report. AB - The present study describes the case of a 63-year-old woman presenting with headache, dizziness and vomiting due to a an ovoid mass in the left pre-bulbar cistern, apparently arising from the lower clivus and the foramen magnum. The clinical history revealed the subtotal removal of a right cerebellar low-grade glioma 15 years previously and subsequent conventional 60-Gy radiotherapy. Notably, following gross total resection, histopathological examination showed microscopic features that resulted in a diagnosis of anaplastic ependymoma. The patient underwent surgery to remove the mass and post-operative chemotherapy with temozolomide. A progressive improvement of neurological signs and symptoms was observed during the postoperative course. At the 6-month follow-up, the patient was free from clinical and radiological recurrence. The unusual features of this rare secondary brain tumor were the extrassial location in the posterior fossa, the unusual age-associated location of the histological subtype and the fact that it closely mimicked a skull-base meningioma. PMID- 26893631 TI - Targeted transplantation of iron oxide-labeled, adipose-derived mesenchymal stem cells in promoting meniscus regeneration following a rabbit massive meniscal defect. AB - Repair of a massive meniscal defect remains a challenge in the clinic. However, targeted magnetic cell delivery, an emerging technique, may be useful in its treatment. The present study aimed to determine the effect of targeted intra articular injection of superparamagnetic iron oxide (SPIO)-labeled adipose derived mesenchymal stem cells (ASCs) in a rabbit model of a massive meniscal defect. ASCs may be directly labeled and almost 100% of the ASCs were labeled with SPIO after 24 h; these SPIO-labeled ASCs may be orientated by magnet. The centrifuged SPIO-labeled ASCs precipitations may be detected by magnetic resonance imaging (MRI). The anterior half of the medial meniscus of 18 New Zealand Rabbits was excised. After 7 days, the rabbits were randomized to injections of 2*106 SPIO-labeled ASCs, 2*106 unlabeled ASCs or saline. Permanent magnets were fixed to the outside of the operated joints for one day, and after 6 and 12 weeks, the knee joints were examined using MRI, gross and histological observation, and Prussian blue staining. Marked hypointense artifacts caused by SPIO-positive cells in the meniscus were detected using MRI. Histological observation revealed that the anterior portion of the meniscus was similar to the native tissue, demonstrating typical fibrochondrocytes surrounded by richer extracellular matrix in the SPIO-ASCs group. Collagen-rich matrix bridging the interface and the neo-meniscus integrated well with its host meniscus. Furthermore, degenerative changes occurred in all groups, but intra-articular injection of SPIO-ASCs or ASCs alleviated these degenerative changes. Prussian blue staining indicated that the implanted ASCs were directly associated with the regenerated tissue. Overall, targeted intra-articular delivery of SPIO-ASCs promoted meniscal regeneration whilst providing protective effects from osteoarthritic damage. PMID- 26893632 TI - Mesenchymal stem cell-conditioned media suppresses inflammation-associated overproliferation of pulmonary artery smooth muscle cells in a rat model of pulmonary hypertension. AB - Inflammation-associated overproliferation of pulmonary artery smooth muscle cells (PASMCs) is considered to be involved in the pathogenesis of pulmonary hypertension (PH). The administration of mesenchymal stem cell-conditioned media (MSC-CM) has displayed benefits in the treatment of PH, however, the exact mechanism has yet to be elucidated. The present study aimed to determine whether MSC-CM is able to suppress overproliferation of PASMCs in PH via immunoregulation. By the administration of MSC-CM to monocrotaline (MCT)-induced PH rats, and the development of an in vitro co-culture system comprised of PASMCs and activated T cells, the therapeutic effects of MSC-CM on PH, and the changes in the expression of correlated factors, including TNF-alpha, calcineurin (CaN) and nuclear factor of activated T cells (NFAT), were assessed. Immunohistochemical staining results indicated that MSC-CM was able to significantly suppress the production of TNF-alpha in MCT-induced PH and co culture systems; and reverse transcription-quantitative polymerase chain reaction results showed significant downregulation of the expression of CaN and NFATc2 in PASMCs (P<0.01). Furthermore, MSC-CM was able to significantly suppress CaN activity and NFATc2 activation (P<0.01), thus inhibiting the overproliferation of PASMCs. Finally, MSC-CM improved abnormalities in hemodynamics and pulmonary histology in MCT-induced PH. In conclusion, the findings of the current study suggest that administration of MSC-CM has the potential to suppress inflammation associated overproliferation of PASMCs due to its immunosuppressive effects in PH and, thus, may serve as a beneficial therapeutic strategy. PMID- 26893633 TI - MRI chemical shift imaging of the fat content of the pancreas and liver of patients with type 2 diabetes mellitus. AB - The present study aimed to investigate the association between the content and distribution of fat in the pancreas and liver in patients with type 2 diabetes mellitus (T2DM). A total of 70 patients newly diagnosed with T2DM (T2DM group) and 30 healthy volunteers (normal control group) were enrolled in the present study. Dual-echo magnetic resonance (MR) chemical shift imaging was used to measure the fat content of the liver and the head, body and tail regions of the pancreas. In addition, the distribution of fat in the various regions of the pancreas, as well as the average fat content of the pancreas versus the liver, were compared. The fat content of the pancreatic head, body and tail regions of the T2DM group were 5.59+/-4.70, 4.80+/-3.75 and 4.89+/-3.86%, respectively. The fat content of these regions in the normal control group were 3.89+/-2.47, 3.30+/ 2.11 and 3.23+/-2.23%, respectively. The average fat content of the pancreas was 5.19+/-3.75% for the T2DM group and 3.47+/-2.00% for the normal control group. The average fat content of the liver was 9.87+/-3.19% for the T2DM group and 7.24+/-2.38% for the normal control group. Therefore, the results from MR chemical shift imaging suggested that there were no significant differences in the distribution of fat between the pancreas of patients newly diagnosed with T2DM and that from the healthy population; however, the average fat content in the pancreas of the T2DM group was significantly higher (F=3.597; P<0.05), as compared with the normal control group. In addition, there was no correlation between the fat contents in the pancreas and liver in patients newly diagnosed with T2DM and the healthy population. PMID- 26893634 TI - Observing the development of the temporomandibular joint in embryonic and post natal mice using various staining methods. AB - The temporomandibular joint (TMJ) is a specialized synovial joint that is essential for the movement and function of the mammalian jaw. The TMJ develops from two mesenchymal condensations, and is composed of the glenoid fossa that originates from the otic capsule by intramembranous ossification, the mandibular condyle of the temporal bone and a fibrocartilagenous articular disc derived from a secondary cartilaginous joint by endochondral ossification. However, the development of the TMJ remains unclear. In the present study, the formation and development of the mouse TMJ was investigated between embryonic day 13.5 and post natal day 180 in order to elucidate the morphological and molecular alterations that occur during this period. TMJ formation appeared to proceed in three stages: Initiation or blastema stage; growth and cavitation stage; and the maturation or completion stage. In order to investigate the activity of certain transcription factors on TMJ formation and development, the expression of extracellular matrix (ECM), sex determining region Y-box 9, runt-related transcription factor 2, Indian hedgehog homolog, Osterix, collagen I, collagen II, aggrecan, total matrix metalloproteinase (MMP), MMP-9 and MMP-13 were detected in the TMJ using in situ and/or immunohistochemistry. The results indicate that the transcription factors, ECM and MMP serve critical functions in the formation and development of the mouse TMJ. In summary, the development of the mouse TMJ was investigated, and the molecular regulation of mouse TMJ formation was partially characterized. The results of the present study may aid the systematic understanding of the physiological processes underlying TMJ formation and development in mice. PMID- 26893635 TI - Application values of clinical nursing pathway in patients with acute cerebral hemorrhage. AB - Acute cerebral hemorrhage accounts for approximately 25% of strokes for elderly patients. Consequently, treatments to improve prognosis should be identified. The aim of the present study was to examine the clinical values of the application of clinical nursing pathway for patients with acute cerebral hemorrhage. Between January 2013 and January 2015, 92 patients diagnosed with acute intracerebral hemorrhage were enrolled in the study based on the guidelines recommended for providing appropriate surgical or conservative treatment and the sequence of admission. The 92 patients were randomly divided into the control and observation groups. Patients in the control group underwent routine nursing mode prior to and after admission, and underwent clinical nursing path model (hierarchical partitioning prior to admission to hospital plus general professional program of nursing in hospital) was applied to the observation group. Barthel index scores for the observation group were significantly higher than that of the control group. The length of hospital stay for patients in the observation group was significantly lower while the average score for patients' satisfaction on nursing care while in hospital was significantly higher than that of the control group, with statistically significant differences (P<0.05). The incidence of complications such as fever, infection, bedsore, gastrointestinal function, electrolyte disturbances, and malnutrition, in the observation group was significantly lower, with statistically significant differences (P<0.05). The functional independence measure (FIM) and Fugl-Meyer scores after 6 months for the observation group were significantly higher, with statistically significant differences (P<0.05). In conclusion, application of the clinical nursing pathway for patients with acute cerebral hemorrhage significantly improved the clinical effects and nursing satisfaction, reduced adverse reactions, and had a greater clinical application value. PMID- 26893636 TI - Effects of transcutaneous acupoint electrical stimulation on the imbalance of Th1, Th2, Th17 and Treg cells following thoracotomy of patients with lung cancer. AB - An imbalance in the various T lymphocytes, including T-helper (Th)1, Th2 and Th17 cells, and regulatory T (Treg) cells, has been associated with immune dysfunction, and may occur following thoracotomy of patients with lung cancer. The use of transcutaneous acupoint electrical stimulation (TAES) has previously been demonstrated to exert immunoregulatory effects; therefore, the present study aimed to evaluate whether TAES was able to attenuate postoperative immune suppression in patients with lung cancer. Thoracic surgical patients with lung cancer (n=27) underwent TAES (frequency, 2/100 Hz; intensity, 4-12 mA) at the bilateral large intestine 4, pericardium 6, small intestine 3 and San Jiao 6 acupuncture points for 30 min, prior to incision, and at 20, 44, 68, 92 and 116 h following thoracotomy. The number of Th1, Th2, Th17 and Treg cells, and the protein and mRNA expression levels of related cytokines were measured by flow cytometry, ELISA and polymerase chain reaction, respectively. The balance of Th1, Th2, Th17 and Treg cells in the peripheral blood of patients with lung cancer was disrupted following thoracotomy. TAES administration increased the percentage of Th1 and Th17 cells, the protein expression levels of interleukin (IL)-2 and interferon-gamma, the mRNA expression levels of T-bet and RAR-related orphan receptor-gammat, and decreased the percentage of Th2 cells, IL-10 protein expression levels, and GATA binding protein 3 mRNA expression levels. The results of the present study demonstrated that TAES was able to partially attenuate the postoperative immune depression of patients with lung cancer, by regulating the balance of Th1, Th2, Th17 and Treg cells, and the expression levels of related cytokines and transcription factors; therefore, TAES may be considered to be a promising strategy for treating postoperative immune dysfunction in patients with lung cancer. PMID- 26893637 TI - Downregulation of CCR5 inhibits the proliferation and invasion of cervical cancer cells and is regulated by microRNA-107. AB - Cervical cancer is among the most prevalent forms of cancer worldwide. C-C chemokine receptor type 5 (CCR5) is hypothesized to be a key functional protein involved in tumorigenesis. However, the role of CCR5 in cervical cancer remains unclear. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to evaluate the mRNA and protein expression levels of CCR5 in human cervical carcinoma tissues. Furthermore, a small interfering RNA was employed to knockdown CCR5 in HeLa and C33A cells. MTT, colony formation and Transwell assays were performed to determine the effects of this knockdown on cell viability, proliferation and invasion. In addition, micro RNA (miR)-107 was identified as a potential candidate regulator of CCR5 using miR prediction algorithms, and the effects of miR-107 and its antisense miR on CCR5 mRNA expression were determined. The results of the present study indicated that CCR5 is overexpressed in human cervical cancer tissues compared with adjacent normal tissues, and its downregulation inhibits cervical cancer cell growth and proliferation. Furthermore, the downregulation of CCR5 appears to suppress cervical cancer cell invasion. Finally, the tumor suppressor miR-107 was able to directly target CCR5 and inhibit its expression. These results suggest that the upregulation of CCR5, which is inhibited by miR-107, may play a carcinogenic role in cervical cancer and could provide a novel therapeutic target in the future. PMID- 26893638 TI - Combined interventional and surgical treatment for a rare case of double patent ductus arteriosus. AB - The present study describes the case of a 2.5-year-old girl with double patent ductus arteriosus (PDA) that was successfully treated following interventional and surgical treatment. Bilateral ductus arteriosus is a very rare condition, which is assumed to occur when the branchial-type arterial system transforms into the mammalian-type arterial system during the development of the aorta and its branches. This case was misdiagnosed as ordinary PDA by echocardiography prior to the first surgery and the surgery was not successful because of poor accessibility. Enhanced computed tomography subsequently showed situs solitus, atrial situs, levocardia, right-sided aortic arch with right-sided descending aorta, an isolated left subclavian artery and double PDA. Interventional treatment was performed and intraoperative aortic arch angiography showed that the descending aorta was the origin of the first funnel-type PDA (PDA-1). The left subclavian artery was not connected to the aorta but was connected to the pulmonary artery with a very narrow winding duct, which was PDA-2. Interventional treatment via PDA-2 also failed because passing a guidewire through the twisted PDA-2 was difficult. The child was immediately transferred to the surgical operation room for double PDA ligation and left subclavian artery reconstruction under median thoracotomy. The surgical procedure succeeded and the patient recovered quickly. The failure of the interventional treatment may be attributed to the difficulty in establishing a path. The soft tip of the hardened guidewire was relatively long. If the hardened part of the wire was sent to the appropriate place to support the pathway, the soft tip would be forced to enter the vertebrobasilar artery system. A similar problem was encountered when the left subclavian artery was selected for intervention. Shortening the length of the soft tip of the hardened guidewire may have enabled smooth completion of the establishment of the pathway. However, this type of hardened guidewire requires specific production. PMID- 26893639 TI - Effects of erythropoietin preconditioning on rat cerebral ischemia-reperfusion injury and the GLT-1/GLAST pathway. AB - The aim of the present study was to investigate whether erythropoietin (EPO) preconditioning affects the expression of glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST) and protects against rat cerebral ischemia-reperfusion injury. A total of 140 Sprague Dawley rats were randomly assigned to one of the following four groups: Sham, EPO-sham, middle cerebral artery occlusion (MCAO) and EPO-MCAO. Neurological function scores were obtained 24, 36 and 72 h after reperfusion. Seventy-two hours after the induction of cerebral ischemia-reperfusion, the number of apoptotic neural cells and the cerebral infarct volume of each group were measured. The mRNA levels of GLT-1 and GLAST were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, while the GLT-1 and GLAST protein levels were assessed using western blotting. The cerebral infarct volume was significantly increased in the MCAO group compared with that in the sham group (P<0.01); however, the infarct volume of the EPO-MCAO group was significantly lower than that of the MCAO group (P<0.01). In addition, the number of apoptotic cells found in the MCAO group was higher than that in the sham group (P<0.01), but the number of apoptotic cells in the EPO-MCAO group was significantly lower than that in the MCAO group (P<0.01). The GLT-1 and GLAST mRNA and protein levels were significantly decreased 72 h after the cerebral ischemia-reperfusion (P<0.01) compared with those in the sham group, whereas the same levels were increased significantly in the EPO-MCAO group relative to those in the MCAO group (P<0.01). In conclusion, EPO preconditioning protected against cerebral ischemia reperfusion injury and upregulated the GLT-1 and GLAST expression. PMID- 26893640 TI - Computed tomography manifestation of acute exacerbation of chronic obstructive pulmonary disease: A pilot study. AB - Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an acute event characterized by the worsening of a patient's respiratory symptoms. To the best of our knowledge, few studies have investigated the computed tomography (CT) manifestation of AECOPD. Thus, the aim of the present study was to examine the CT manifestations during AECOPD. In total, 40 patients with AECOPD admitted to the emergency department were enrolled. CT images obtained at the time of exacerbation and at the 3-month follow-up were paired. Clinical characteristics and routine blood test results were also recorded. Airway dimensions and attenuation per patient were quantified from the 3rd to the 6th generation of four bronchi by Airway Inspector Slicer 2.8. The emphysema extent was also quantified and lung infiltration was detected, classified and measured. The CT images showed an increased wall area percentage (WA%) and increased mean and peak wall attenuation during the AECOPD; however, the extent of emphysema did not change significantly. In total, 60% of AECOPD patients presented with lung infiltration, compared with those at the follow-up CT scanning. The presence and extent of segmental distribution consolidation was correlated with the neutrophil percentage (N%), with a statistically significant difference observed. The total volume of lung parenchymal infiltration was correlated with the white blood cell (WBC) count and N%; however, no significant correlations were detected between the presence or extent of acinar shadow, air space consolidation with lobular distribution, ground-glass attenuation with lobular distribution, thickening of the interlobular septa and signs of infection (including the number of main symptoms, body temperature, WBC count and N%). The WA%, mean wall attenuation and peak wall attenuation increased during AECOPD, but the emphysema extent was unchanged. Lung infiltration existed frequently; however, only consolidation with segmental distribution appeared to be associated with bacterial infection. PMID- 26893641 TI - Increased 3beta-hydroxysteroid dehydrogenase 2 and 17alpha-hydroxylase activities in a virilized adolescent female with adrenal adenoma: A case report. AB - In the present study, the case of a female patient with pseudo-hermaphrodism caused by an androgen-producing adrenocortical tumor is presented, and the possible mechanism is investigated. The expression of the luteinizing hormone/human chorionic gonadotrophin (LH/hCG) receptor in tumor tissues and normal adrenal tissues was analyzed using immunohistochemistry. Furthermore, the activities of 3beta-hydroxysteroid dehydrogenase 2 (HSD2), cytochrome P450 17alpha-hydroxylase (CYP17) and 17beta-hydroxysteroid dehydrogenase 3 (HSD3) enzymes were measured using enzyme-linked immunosorbent assay, and the expression levels of 3beta-HSD2, 17beta-HSD3, CYP17 and LH/hCG receptor mRNA were determined by quantitative polymerase chain reaction (qPCR). Immunohistochemical staining for the LH/hCG receptor was negative in the tumor tissue and positive in the normal adrenal tissue. The activities of 3beta-HSD2 and CYP17 in the tumor tissue were higher than those in the normal tissue (P<0.01), whereas the activity of 17beta-HSD3 was lower (P<0.01). The mRNA levels of 3beta-HSD2 and CYP17 were higher (P<0.01) and the levels of 17beta-HSD3 and LH/hCG receptor were lower (P<0.01) in the tumor tissue compared with those of the normal tissue. In conclusion, in the present study, a rare case of virilization by an androgen producing adrenocortical tumor is present. The results indicate that it may be associated with increased activities of 3beta-HSD2 and CYP17 but not with the expression of the LH/hCG receptor. PMID- 26893642 TI - Effect of an EDA-A1 gene mutant on the proliferation and cell cycle distribution of cultured human umbilical vein endothelial cells. AB - Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P<0.01), whereas the wild-type EDA-A1 gene did not cause such growth inhibition (P>0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P<0.05). These results indicate that compared with the wild-type gene, transfection with a mutant EDA-A1 gene inhibited the proliferation and cell cycle of cultured HUVECs. PMID- 26893643 TI - Henoch-Schonlein purpura following high-voltage electric burn injury: A case report and review of the literature. AB - Henoch-Schonlein Purpura (HSP) is a systemic vasculitis of unknown cause, with immune-mediated inflammation of the small vessels, which is characterized by a series of clinical symptoms, such as purpuric rash, colicky abdominal pain, arthritis and acute glomerulonephritis. Twenty-one days following a high-voltage electrical burn injury, a 40-year-old man developed classic clinical symptoms of HSP, including purpuric rash on bilateral lower extremities and abdominal pain. The patient was diagnosed with HSP associated with high-voltage burn injury, which is an extremely rare phenomenon. The diagnosis was based on the clinical manifestations of purpuric rash, abdominal pain and arthralgia, as well as the findings of laboratory examinations [increased levels of serum immunoglobulin A (11.6g/l) and complements C3 (9.6 g/l) and C4 (7.6 g/l), and a positive fecal occult blood test]. The patient was treated with antihistamines (loratadine tablets; 10 mg/day), anti-inflammatory medication (methylprednisolone sodium succinate; 40 mg/day) and oral omeprazole magnesium. The symptoms gradually decreased within 2 weeks from treatment and no abnormality was observed at the 3 , 6- and 12-month follow-ups. In patients who have suffered an electrical burn injury, this autoimmune disease may be caused by long-term inflammation. Therefore, examination of the liver and kidney functions of such patients is important in order to decrease the risk of post-traumatic immune system dysfunction. PMID- 26893644 TI - Proton pump inhibitor-induced exfoliative dermatitis: A case report. AB - A 74-year-old female patient was admitted to hospital following a road accident with pains in the chest, abdomen, waist, back, nose, left wrist and lower limbs. After 1 week, the patient presented with gastrointestinal bleeding, and thus was treated with protein pump inhibitors (PPIs), including lansoprazole, esomeprazole and omeprazole enteric-coated tablets, in order to inhibit acid secretion and attenuate bleeding. However, the patient developed skin rashes on the chest and right lower limb and foot 28 days following treatment initiation. The skin rashes spread and ulcerated after 3 days, and were associated with tracheal mucosal injury and hemoptysis. Subsequently, treatment of the patient with PPIs was terminated, after which the tracheal hemoptysis and skin rashes markedly improved. In addition, no new skin rashes appeared following termination of the PPI treatment. In the present case, long-term treatment of an elderly patient with PPIs may have induced exfoliative dermatitis, due to hepatic ischemia, hypoxia and acute renal failure, which may have decreased the metabolism of PPIs, resulting in the accumulation of PPI metabolites. PMID- 26893645 TI - Effect of pERK2 on extracellular matrix turnover of the fibrotic joint capsule in a post-traumatic joint contracture model. AB - Lentivirus (LV)-mediated extracellular signal-regulated kinase (ERK)2 small interfering RNA (siRNA) has previously been demonstrated to reduce post-traumatic joint contractures: In the present study, the effect of ERK2 siRNA on extracellular matrix turnover within fibrotic joint capsules in post-traumatic joint contractures was examined. Rats were randomly assigned to one of three groups as follows: The non-operated control (CON), operated contracture (ORC) and contracture-treatment (CNT) groups. Representative post-traumatic joint contracture was created through 8 weeks of immobilization following intra articular injury. In the CNT group, LV-mediated ERK2 siRNA was injected into the model knee at days 3 and 7 after surgery. The posterior joint capsule was examined by western blotting, histology and immunohistochemistry to evaluate alterations in ERK2, phosphorylated (p)ERK2, total collagen, collagen I, collagen III, matrix metalloproteinase (MMP)-1, MMP-13 and tissue inhibitor of metalloproteinase (TIMP)-13. In the ORC group, pERK2 was elevated and total collagen, collagen I, MMP-1 and MMP-13 were significantly increased (P<0.01 vs. CON group); however, these were significantly decreased in the CNT group, and pERK2 was downregulated (P<0.01 vs. ORC group). Collagen III and TIMP-13 were markedly decreased in the ORC group (P<0.01 vs. CON group), but elevated in the CNT group (P<0.01 vs. ORC group). The present res4ults demonstrate unique pathological changes of the fibrotic joint capsule that are responsible for joint contracture following traumatic injury, and reveal that extracellular matrix turnover can be affected by pERK2. PMID- 26893646 TI - Synthesis of Co3O4 nanoparticles with block and sphere morphology, and investigation into the influence of morphology on biological toxicity. AB - In the present study, cobalt oxide (Co3O4) magnetic nanoparticles with block and sphere morphologies were synthesized using various surfactants, and the toxicity of the particles was analyzed by monitoring biomarkers of nanoparticle toxicity in zebrafish. The use of tartarate as a surfactant produced highly crystalline blocks of Co3O4 nanoparticles with pores on the sides, whereas citrate lead to the formation of nanoparticles with a spherical morphology. Co3O4 structure, crystallinity, size and morphology were studied using X-ray diffractogram and field emission scanning electron microscopy. Following an increase in nanoparticle concentration from 1 to 200 ppm, there was a corresponding increase in nitric oxide (NO) generation, induced by both types of nanoparticles [Co3O4-NP B (block), r=0.953; Co3O4-NP-S (sphere), r=1.140]. Comparative analyses indicated that both types of nanoparticle produced significant stimulation at >=5 ppm (P<0.05) compared with a control. Upon analyzing the effect of nanoparticle morphology on NO generation, it was observed that Co3O4-NP-S was more effective compared with Co3O4-NP-B (5 and 100 ppm, P<0.05; 200 ppm, P<0.01). Exposure to both types of nanoparticles produced reduction in liver glutathione (GSH) activity with corresponding increase in dose (Co3O4-NP-B, r=-0.359; Co3O4-NP-S, r=-0.429). However, subsequent analyses indicated that Co3O4-NP-B was more potent in inhibiting liver GSH activity compared with Co3O4-NP-S. Co3O4-NP-B proved to be toxic at 5 ppm (P<0.05) and GSH activity was almost completely inhibited at 200 ppm. A similar toxicity was observed with both types of Co3O4-NPs against brain levels of acetylcholinesterase (AChE; Co3O4-NP-B, r=-0.180; Co3O4-NP-S, r= 0.230), indicating the ability of synthesized Co3O4-NPs to cross the blood-brain barrier and produce neuronal toxicity. Co3O4-NP-B showed increased inhibition of brain AChE activity compared with Co3O4-NP-S (1,5, and 10 ppm, P<0.05; 50, 100 and 200 ppm, P<0.01). These results suggested that the morphology of nanoparticle and surface area contribute to toxicity, which may have implications for their biological application. PMID- 26893647 TI - Fibroblastic reticular cell tumor of the breast: A case report and review of the literature. AB - Fibroblastic reticular cells (FBRCs) are basic mesenchymal cells that belong to the dendritic cell family. Primary extranodal FBRC tumor (FRCT) cases are rare, with only 19 cases reported in the literature thus far. However, none of these cases originated in the breast tissue. To the best of our knowledge, the present study reported the first FRCT case of the breast in a 57-year-old woman. The patient complained of a painless mass that was located in the right breast and was ~3.5*2.5 cm in size. The patient underwent modified radical mastectomy subsequent to the diagnosis of FRCT after analysis of the lumpectomy specimen. Pathological examination revealed that the tumor was mainly composed of oval and spindle cells, and was infiltrated with lymphocytes and plasma cells. The tumor cells were immunoreactive for vimentin and negative for CD21, CD35 and S-100 protein. Six axillary lymph nodes were found to have been involved. Following surgery, the patient received four cycles of mesna, doxorubicin, ifosfamide and dacarbazine regimen chemotherapy (70 mg adriamycin day 1; 2.0 g ifosfamided days 1-3; 0.4 g dacarbazine day 1-3), which cycled every 21 days. The patient was uneventfully followed-up for 20 months following chemotherapy. In conclusion, the present study reported what appeared to be the first case of primary breast FRCT. The diagnosis, treatment and prognosis details presented in this study will help improve the diagnosis of the disease. PMID- 26893648 TI - Protein kinase C-beta inhibitor treatment attenuates hepatic ischemia and reperfusion injury in diabetic rats. AB - Hepatic ischemia and reperfusion (I/R) injury plays an active role in hepatic resection and transplantation. While the effects of protein kinase C (PKC)-betaII activation and the role of PKC-beta inhibitors are well understood in myocardial I/R in diabetes, they remain unclear in liver I/R. The aim of this study was to explore the effect of PKC-beta inhibition and the potential mechanism by which PKC-beta inhibitor treatment protects against hepatic I/R injury in diabetic rats. Diabetic rats were established and randomized into two groups. These were an untreated group (n=10), which did not receive any treatment, and a treatment group (n=10), orally treated with ruboxistaurin at a dose of 5 mg/kg/day for 2 weeks. The rats from the two groups were subjected to hepatic I/R. Aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels were measured by enzymatic methods at 1, 3 and 5 h after I/R. Tumor necrosis factor-alpha (TNF alpha) and intercellular adhesion molecule 1 (ICAM-1) were examined by enzyme linked immunosorbent assay at the same time-points. Nuclear factor-kappaB (NF kappaB) p65 expression was analyzed by immunofluorescence and western blotting. Apoptosis of hepatic cells was examined by the western blot analysis of caspase 3 expression and by DNA ladder analysis. Pathological changes were examined using light and electron microscopy. Serum AST and LDH levels in the PKC-beta inhibitor treatment group were diminished compared with those in the untreated group (P<0.01). Serum TNF-alpha and ICAM-1 (P<0.01) levels were also decreased at different time-points in the PKC-beta inhibitor treatment group. The relative expression of NF-kappaB p65 and caspase 3 in the hepatic tissue was weakened in the PKC-beta inhibitor treatment group compared with that in the untreated group (P<0.01). Pathological changes in hepatic tissue were attenuated by the PKC-beta inhibitor. In conclusion, PKC-beta inhibitor treatment protected against liver I/R injury in diabetic rats. The mechanisms probably involved the attenuation of microvascular injury, reduced transport of injury-associated factors and diminishment of the activation of NF-kappaB p65. PMID- 26893649 TI - High expression of VEGF and PI3K in glioma stem cells provides new criteria for the grading of gliomas. AB - Glioma is a type of tumor derived from glial cells, which is associated with a high level of incidence and mortality. At present, the generation of a fast and efficient method to evaluate the malignancy grade of glioma is required. Cancer stem cells (CSCs) are currently attracting attention in oncological studies; therefore, the present study aimed to investigate novel biomarkers of glioma CSCs, in order to provide new criteria for the grading of glioma. The mRNA expression levels of CD133, (sex determining region Y)-box 2, nestin, vascular endothelial growth factor (VEGF) and phosphoinositide-3-kinase (PI3K) were detected in 15 human samples of high-malignancy glioma and 12 human samples of low-malignancy glioma in vitro. The mRNA expression levels of VEGF and PI3K were higher in the high-malignancy group, as compared with in the low-malignancy group. In conclusion, the mRNA expression levels of VEGF and PI3K in glioma CSCs may be considered a novel criteria for the grading of glioma. PMID- 26893650 TI - Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation. AB - The alleviation of brain injury is a key issue following cardiopulmonary resuscitation (CPR). Hydrogen sulfide (H2S) is hypothesized to be involved in the pathophysiological process of ischemia-reperfusion injury, and exerts a protective effect on neurons. The aim of the present study was to investigate the effects of H2S on neural functions following cardiac arrest (CA) in rats. A total of 60 rats were allocated at random into three groups. CA was induced to establish the model and CPR was performed after 6 min. Subsequently, sodium hydrosulfide (NaHS), hydroxylamine or saline was administered to the rats. Serum levels of H2S, neuron-specific enolase (NSE) and S100beta were determined following CPR. In addition, neurological deficit scoring (NDS), the beam walking test (BWT), prehensile traction test and Morris water maze experiment were conducted. Neuronal apoptosis rates were detected in the hippocampal region following sacrifice. After CPR, as the H2S levels increased or decreased, the serum NSE and S100beta concentrations decreased or increased, respectively (P<0.0w. The NDS results of the NaHS group were improved compared with those of the hydroxylamine group at 24 h after CPR (P<0.05). In the Morris water maze experiment, BWT and prehensile traction test the animals in the NaHS group performed best and rats in the hydroxylamine group performed worst. At day 7, the apoptotic index and the expression of caspase-3 were reduced in the hippocampal CA1 region, while the expression of Bcl-2 increased in the NaHS group; and results of the hydroxylamine group were in contrast. Therefore, the results of the present study indicate that H2S is able to improve neural function in rats following CPR. PMID- 26893651 TI - Expression levels of cytokines and chemokines increase in human peripheral blood mononuclear cells stimulated by activation of the Toll-like receptor 5 pathway. AB - Recognition of pathogen-associated molecular patterns by Toll-like receptors (TLRs) activates innate and adaptive immune responses. Among the 11 members of the human TLR family, TLR-5 is known to play an important role in the defense against bacterial invasion by binding to flagellin, a conserved component of bacteria. Previous studies have demonstrated that the activation of TLR-5 induces the expression of interleukin (IL)-10, IL-12 and interferon-beta. However, the aim of the present study was to analyze the expression of a wider range of immune related molecules upon stimulation with a TLR-5 agonist. Following isolation from healthy volunteers, peripheral blood mononuclear cells (PBMCs) were stimulated with flagellin, a TLR-5 agonist. At 4 h after stimulation, quantitative polymerase chain reaction (PCR) and an antibody chip array were conducted to determine the mRNA expression levels of immune molecules and the protein secretion of immune molecules in the supernatant, respectively. The PCR results revealed that activation of TLR-5 significantly influenced the expression of a number of important molecules. In addition, the antibody chip array demonstrated the induction (IL-8) and inhibition [monocyte chemoattractant protein (MCP)-1, MCP-3 and macrophage inflammatory protein-1alpha) of protein secretion following TLR-5 stimulation. Therefore, the present study demonstrated the importance of TLR-5 in regulating the biological function of PBMCs. In the future, research should focus on the roles of the candidate molecules in TLR-5-mediating functions. PMID- 26893652 TI - Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Abeta1-42 expression. AB - Oxidative stress and ageing are important factors contributing to the pathogenesis of Alzheimer's disease (AD), which is associated with neuronal damage and beta-amyloid (Abeta) deposition. The p66shc adaptor protein is important for the regulation of oxidative stress and ageing. In the present study, SH-SY5Y human neuroblastoma cells were treated with anisomycin in order to establish a cell model of oxidative stress-induced neuronal damage. The results from quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting demonstrated that anisomycin was able to stimulate the secretion of Abeta1-42 from SH-SY5Y cells and upregulate the expression levels of p66shc, which was associated with concomitant damage to SH-SY5Y cells. In addition, the protective effects of various small molecule compounds with antioxidant properties against neuronal damage were evaluated. Notably, treatment of SH-SY5Y cells with gallic acid was associated with significant downregulation of p66shc protein expression levels, reduced anisomycin-induced secretion of Abeta1-42, and increased superoxide dismutase activity and acetylcholine secretion levels. The results of the present study suggested that anisomycin is able to promote oxidative neuronal damage by inducing the secretion of Abeta1-42 from neurons and increasing the neuronal expression of p66shc, and this damage may be attenuated by treatment with gallic acid. Therefore, gallic acid and similar small molecule compounds may be considered for the alleviation of neuronal oxidative stress injury in patients with AD. PMID- 26893653 TI - Ibuprofen targets neuronal pentraxins expresion and improves cognitive function in mouse model of AlCl3-induced neurotoxicity. AB - Aluminum is known to exert neurotoxic effects associated with various neurodegenerative disorders, including Alzheimer's disease (AD). Ibuprofen is a well-known non-steroidal anti-inflammatory drug, which has demonstrated potential efficacy in the treatment of numerous inflammatory and neurodegenerative disorders, including AD. The present study aimed to investigate the protective effects of ibuprofen on cognitive function, and the expression levels of neuronal pentraxins (NPs) and interleukin (IL)-1beta in an aluminum chloride (AlCl3) induced mouse model of neurotoxicity. The effects of ibuprofen (100 mg/kg/day for 12 days) on learning and memory were evaluated in the AlCl3-induced neurotoxic mice using a Morris water maze and open field tests. In addition, ibuprofen was assessed for its effects on the expression levels of NPs and IL-1beta in the hippocampus, cortex and amygdala of the brain. Treatment of the AlCl3-treated mice with ibuprofen decreased anxiety levels (6.90+/-0.34 min) compared with the AlCl3-treated group (1.80+/-0.29 min), as indicated by the time spent in the central area in an open field test. Furthermore, the expression levels of NP1 (1.32+/-0.47) and IL-1beta (0.99+/-0.21) were significantly decreased in the hippocampus of mice following ibuprofen treatment, as compared with the AlCl3 treated mice (8.62+/-1.54 and 7.47+/-0.53, respectively). In the present study, ibuprofen was able to target novel structures in order to attenuate the inflammation associated with an AlCl3-induced mouse model of neurotoxicity; thus suggesting that ibuprofen may be considered a potential therapeutic option for the treatment of neurodegenerative diseases, including AD. PMID- 26893654 TI - Prognostic significance of serum insulin-like growth factor-1 in patients with hepatocellular carcinoma following transarterial chemoembolization. AB - Insulin-like growth factor-1 (IGF-1) is an effective survival factor that is involved in the development and progression of various tumors. The aim of the present study was to investigate whether baseline serum IGF-1 levels are associated with time to progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) who have undergone transarterial chemoembolization (TACE). A total of 145 patients with HCC who underwent TACE as an initial treatment were enrolled in the study. Baseline serum IGF-1 levels were detected using enzyme-linked immunosorbent assay (ELISA) kits. The patients were followed up for a median follow-up period of 47 months (range, 10.6-69.3 months). During the follow-up, 98 patients (76.6%) experienced disease progression and 59 patients (46.1%) succumbed. The serum IGF-1 level was found to be significantly associated with hepatitis infection status, Child-Pugh class, bilirubin level, tumor size and nodularity, vascular invasion and the Barcelona Clinic Liver Cancer (BCLC) stage. Multivariate analysis was conducted, which indicated that BCLC stage, vascular invasion and serum IGF-1 were independent risk factors for disease progression. When clinical factors were examined as potential independent risk factors for OS, only advanced BCLC stage and low serum IGF-1 levels were found to be significantly associated with poorer OS. These results suggest that serum IGF-1 may serve as a predictor of the prognosis of patients with HCC undergoing TACE. PMID- 26893655 TI - Fangchinoline inhibits the proliferation of SPC-A-1 lung cancer cells by blocking cell cycle progression. AB - Fangchinoline (Fan) is a bioactive compound isolated from the Chinese herb Stephania tetrandra S. Moore (Fen Fang Ji). The aim of the present study was to investigate the effect of Fan on the proliferation of SPC-A-1 lung cancer cells, and to define the associated molecular mechanisms. Following treatment with Fan, Cell Counting Kit-8, phase contrast imaging and Giemsa staining assays were used to detect cell viability; flow cytometry was performed to analyze the cell cycle distribution; and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to investigate changes in the expression levels of cell cycle-associated genes and proteins. In the present study, treatment with Fan markedly inhibited the proliferation of SPC-A-1 lung cancer cells and significantly increased the percentage of cells in the G0/G1 phase of the cell cycle in a dose-dependent manner (P<0.05 for 2.5-5 um; P<0.01 for 10 um), whereas the percentage of cells in the S and G2/M phases were significantly reduced following treatment (P<0.05 for 5 um; P<0.01 for 10 um). Mechanistically, Fan significantly reduced the mRNA expression levels of cyclin D1, cyclin-dependent kinase 4 (CDK4) and CDK6 (P<0.05 for 2.5-5 um; P<0.01 for 10 um), which are key genes in the regulation of the G0/G1 phase of the cell cycle. Furthermore, treatment with Fan also decreased the expression of phosphorylated retinoblastoma (Rb) and E2F transcription factor-1 (E2F-1) proteins (P<0.05 for 5 um; P<0.01 for 10 um). In summary, the present study demonstrated that Fan inhibited the proliferation of SPC-A-1 lung cancer cells and induced cell cycle arrest at the G0/G1 phase. These effects may be mediated by the downregulation of cellular CDK4, CDK6 and cyclin D1 levels, thus leading to hypophosphorylation of Rb and subsequent suppression of E2F-1 activity. Therefore, the present results suggest that Fan may be a potential drug candidate for the prevention of lung cancer. PMID- 26893656 TI - Gallic acid decreases hepatitis C virus expression through its antioxidant capacity. AB - Gallic acid (GA) is a natural phenolic compound that possesses various biological effects, including antioxidant, anti-inflammatory, antibiotic, anticancer, antiviral and cardiovascular protection activities. In addition, numerous studies have reported that antioxidants possess antiviral activities. Hepatitis C virus (HCV) is one of the most important causes of chronic liver diseases worldwide, but until recently, only a small number of antiviral agents had been developed against HCV. Therefore, the present study investigated whether GA exhibits an anti-HCV activity. The effects of GA on HCV expression were examined using a subgenomic HCV replicon cell culture system that expressed HCV nonstructural proteins (NSs). In addition, GA cytotoxicity was evaluated at concentrations between 100-600 mg/ml using an MTT assay. Huh-7 replicon cells were incubated with 300 mg/ml GA for different times, and the HCV-RNA and protein levels were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control and reactive oxygen species (ROS) production was measured during the exposure. The results indicated that GA did not produce a statistically significant cytotoxicity in parental and HCV replicon cells. Furthermore, GA downregulated the expression levels of NS5A-HCV protein (~55%) and HCV-RNA (~50%) in a time-dependent manner compared with the levels in untreated cells. Notably, GA treatment decreased ROS production at the early time points of exposure in cells expressing HCV proteins. Similar results were obtained upon PDTC exposure. These findings suggest that the antioxidant capacity of GA may be involved in the downregulation of HCV replication in hepatoma cells. PMID- 26893658 TI - IL-17 promotes keratinocyte proliferation via the downregulation of C/EBPalpha. AB - Psoriasis vulgaris is a common chronic inflammatory skin disease characterized by the hyperproliferation and abnormal differentiation of keratinocytes. CCATT/enhancer binding protein alpha (C/EBPalpha) is abundant in the epidermis and is associated with the proliferation of keratinocytes. However, the role of C/EBPalpha in the proliferation of keratinocytes and the pathogenesis of psoriasis vulgaris are yet to be elucidated. In the present study, using two-step immunohistochemistry, the expression levels of C/EBPalpha and Ki-67 were examined in skin biopsies harvested from 30 patients with psoriasis vulgaris and 30 healthy control subjects. The proliferation index (PI) was calculated and the correlation between C/EBPalpha expression levels and the PI was assessed using Pearson's correlation coefficient. In addition, the effect on HaCaT immortalized human keratinocytic cells of treatment with various concentrations of interleukin (IL)-17 was investigated. Subsequently, cell proliferation rates were examined using a Cell Counting kit-8 assay and the mRNA and protein expression levels of C/EBPalpha were analyzed using semiquantitative reverse transcription-polymerase chain reaction and western blotting, respectively, in order to analyze the effects of IL-17 stimulation on C/EBPalpha expression levels. C/EBPalpha expression was predominantly detected in the cytoplasm of the keratinocytes and C/EBPalpha expression levels were significantly lower in the psoriatic lesions (P<0.05), as compared with the control group. An inverse correlation was detected between the expression levels of C/EBPalpha and the PI in the psoriatic lesions. Furthermore, a significant increase in the cell proliferation rate and significant reductions in the mRNA and protein expression levels of C/EBPalpha were detected in HaCaT cells following treatment with IL-17. These results demonstrated that C/EBPalpha may act as a downstream target of IL-17 and may be associated with the pathogenesis of psoriasis. PMID- 26893657 TI - Upregulation of microRNA-375 increases the cisplatin-sensitivity of human gastric cancer cells by regulating ERBB2. AB - Resistance to chemotherapy is a major challenge in the effective treatment of patients with gastric cancer; however, the mechanisms underlying chemoresistance in gastric cancer cells are yet to be elucidated. MicroRNAs (miRNAs) have previously been associated with cancer progression and sensitivity to chemotherapy; therefore, the present study aimed to identify miRNAs that may influence the sensitivity of human gastric cancer cells to cisplatin (DDP) treatment. Initially, miRNAs that were differentially expressed between the DDP sensitive SGC7901 human gastric cancer cell line and DDP-resistant SGC7901/DDP cell line were identified using high-throughput sequencing technology. miRNA-375 (miR-375), which was shown to be downregulated in the SGC7901/DDP cells, has previously been associated with numerous types of cancer; however, to the best of our knowledge, a role for miR-375 in the DDP-sensitivity of gastric cancer cells has yet to be explored. In the present study, the expression levels of miR-375 were significantly downregulated in the SGC7901/DDP cells, as compared with the SGC7901 cells, as demonstrated by reverse transcription-quantitative polymerase chain reaction. In addition, upregulation of miR-375 significantly enhanced the anti-proliferative and apoptosis-inducing effects of DDP, whereas downregulation of miR-375 decreased these effects. Subsequently, western blot analysis demonstrated that upregulation of miR-375 in the SGC7901/DDP cells increased their sensitivity to DDP treatment via regulating the protein expression levels of erb-b2 receptor tyrosine kinase 2 and phosphorylated-Akt. The results of the present study indicate that the expression levels of miR-375 may influence the sensitivity of human gastric cancer cells to the effects of DDP; thus suggesting that a combination of miR-375 regulation and DDP may be considered a novel strategy in the treatment of patients with chemoresistant gastric cancer. PMID- 26893659 TI - SPAG9 controls the cell motility, invasion and angiogenesis of human osteosarcoma cells. AB - Sperm-associated antigen 9 (SPAG9) is an oncoprotein involved in the progression of various human malignancies; however, its role in osteosarcoma (OS) remains poorly evaluated. The present study used MatrigelTM cell migration and invasion assays, tube formation assay, Cell Counting kit-8, quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay to investigate the role of SPAG9 in OS cell motility, invasion and angiogenesis. The results of the present study demonstrated that SPAG9 expression was upregulated in OS tissues, as compared with adjacent normal tissues, and knockdown of SPAG9 in an OS cell line inhibited cell motility and invasion via inactivation of metalloproteinase (MMP)-2 and MMP-9. Furthermore, the present study demonstrated that silencing of SPAG9 in OS cells inhibited tube formation, the proliferation of human umbilical vascular endothelial cells, and suppressed vascular endothelial growth factor (VEGF) expression and secretion, contributing to a reduction in angiogenesis. The results of the present study indicated that SPAG9 may be an important regulator in OS and may be involved in metastasis. Therefore SPAG9 may be a promising target for the treatment of metastatic OS. PMID- 26893660 TI - IGF-1 and VEGF can be used as prognostic indicators for patients with uterine fibroids treated with uterine artery embolization. AB - The aim of the present study was to investigate the association between serum vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF 1) levels and the prognosis of patients with uterine fibroids following uterine artery embolization (UAE) treatment. A total of 70 patients with uterine fibroids and 20 healthy controls were enrolled in this study between 2012 and 2014. The serum levels of IGF-1 and VEGF were measured using ELISA. Multiple-factor analysis was performed to assess the association between serum levels of IGF 1/VEGF and certain clinical characteristics, including size, location, number of uterine fibroids and adenomyosis. Progression-free survival curves were analyzed using the Kaplan-Meier method. The serum levels of IGF-1 and VEGF in patients with uterine fibroids prior to UAE treatment were significantly higher than those in controls (P<0.05). At 1 week after UAE treatment, the serum levels of IGF-1 and VEGF were significantly lower compared with those prior to UAE treatment. The serum levels of IGF-1 and VEGF at 1 or 3 months after UAE treatment were significantly higher than those at 1 week after UAE treatment. The serum levels of IGF-1 and VEGF were significantly correlated with the clinical characteristics of uterine fibroids (P<0.05). Lower levels of IGF-1 and VEGF in the serum following UAE treatment were associated with an enhanced progression-free survival of patients. In conclusion, the levels of IGF-1 and VEGF in the serum following UAE treatment can be used as indicators of prognosis in patients with uterine fibroids. PMID- 26893661 TI - Sevoflurane inhibits the antioxidant capacity of erythrocytes. AB - The aim of the present study was to observe the effects of sevoflurane on the antioxidant capacity, endothelial nitric oxide synthase (eNOS) content and lifespan of erythrocytes. A 2% erythrocyte suspension was prepared from whole blood collected from healthy volunteers and then treated with sevoflurane at different concentrations (group A, 0%; group S1, 1%; group S3, 3%; and group S5, 5%), in the presence or absence of 200 umol/l hydrogen peroxide (H2O2, or H in group names). In order to evaluate the effects of sevoflurane on the antioxidant capacity and NO metabolism of erythrocytes, the hemolysis rate, catalase (CAT) content and eNOS content were determined, while the labeled phosphatidylserine rate and forward scatter of erythrocytes were detected using flow cytometry. Group S3 showed the highest hemolysis rate in the absence H2O2, while treatment with H2O2 increased the hemolysis rate of groups S1 and S3 (P=0.027). The CAT content in groups treated with sevoflurane was significantly lower compared with that in the control (group A, air group). The CAT content in groups S1+H, S3+H and S5+H remained significantly lower compared with group A+H (P<0.05). The eNOS content of group A was similar to that of group S3, while the content in group S1 was similar to that in group S5. In addition, the eNOS content of groups A and S3 increased, while that of groups S1 and S5 was reduced upon H2O2 treatment (P<0.05). The results indicated that sevoflurane reduced the antioxidative activity of erythrocytes, decreasing the resistant ability to H2O2 damage and increasing the hemolysis rate. The underlying mechanism may be associated with the inhibitory effect on the CAT activity of erythrocytes. Sevoflurane also inhibited the generation of nitric oxide in erythrocytes and reduced the tolerance of erythrocytes against oxidative stress damage due to H2O2. PMID- 26893662 TI - Paeoniflorin ameliorates rheumatoid arthritis in rat models through oxidative stress, inflammation and cyclooxygenase 2. AB - Paeoniflorin has anti-inflammatory, anti-allergy, immune regulatory and pain relieving effects, amongst other roles. However, the mechanisms underlying the protective effects of paeoniflorin on rheumatoid arthritis (RA) remain under investigation; the objective of the current study was to evaluate these protective effects in the context of an RA model. Rats were randomly divided into 5 groups, as follows: The control group, the RA rat model group, and the paeoniflorin groups, in which paeoniflorin was administered at concentrations of 5, 10 and 20 mg/kg for 3 weeks. The pain thresholds and arthritic symptoms of the RA rats were measured. Oxidative stress and inflammatory cytokines were also analyzed and western blot analysis was used to evaluate cyclooxygenase-2 (COX-2) protein expression levels. Paeoniflorin significantly increased the pain threshold and decreased the arthritic symptoms in the RA rat model. Notably, paeoniflorin reduced the malondialdehyde concentration and increased the activity of superoxide dismutase, catalase and glutathione peroxidase. Furthermore, paeoniflorin attenuated the activity of nuclear factor-kappaB p65 unit, tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6, and reduced the COX-2 protein expression level. The present study indicates that paeoniflorin ameliorates disease in rat models of RA through oxidative stress, inflammation and alterations to COX-2 expression. PMID- 26893663 TI - alpha1-blockers for the reduction of ureteric stent-related symptoms: A systematic review and meta-analysis. AB - The present meta-analysis aimed to evaluate the current evidence for the use of alpha1-blockers in relieving ureteric stent-related symptoms (USS). Electronic databases, including PubMed, Embase and Cochrane Library, were searched and two independent reviewers identified relevant parallel randomized controlled trials (RCTs), assessed trial quality and extracted data. Review Manager (version 5.2) was used to conduct a meta-analysis of the data. Significant advantages were demonstrated in the treatment group based on International Prostate Symptom Score (IPSS), voiding symptom sub-scores [mean difference (MD), -2.66; 95% confidence interval (CI), (-4.36, -0.96)], Ureteral Stent Symptom Questionnaire (USSQ) urinary symptoms score (MD, -5.84; 95%CI, -9.35 to -2.33), IPSS quality of life score (MD, -1.46; 95%CI, -2.64 to -0.28) USSQ quality of life score (MD, -0.69; 95%CI, -1.10 to -0.28), USSQ pain score (MD, -3.97; 95%CI, -5.52 to -2.42), Visual Analog Pain Scale (MD, -1.53; 95%CI, -2.25 to -0.80) and USSQ general health score (MD, -1.82; 95%CI, -2.47 to -1.18). No significant differences were detected from the following results: IPSS storage symptom sub-score (MD, -0.93; 95%CI, -2.28 to 0.43), USSQ sexual matters score (MD, -0.10; 95%CI, -0.79 to 0.59), USSQ work performance score (MD, 1.64; 95%CI, -2.18 to 5.47) and USSQ additional problems score (MD, -2.02; 95%CI, -4.55 to 0.52). However, significant between-trial heterogeneity was detected following statistical analysis and there were insufficient data to trace its source. The existing RCT data supported the hypothesis that alpha1-blockers beneficially influence pain, urinary symptoms and the quality of life of patients with an indwelling ureteral stent. PMID- 26893664 TI - Enhanced anticancer effect of ABT-737 in combination with naringenin on gastric cancer cells. AB - Gastric cancer is the second leading cause of cancer-associated mortality and is a frequently occurring cancer worldwide. Multiple drug resistance of gastric cancer cells leads to the poor prognosis. In addition, overexpression of anti apoptotic protein B-cell lymphoma (Bcl)-2 have been demonstrated in various cancer cells and is closely associated with drug resistance and poor prognosis. Naringenin is a flavonoid that has antimutagenic and anticarcinogenic activities in numerous cancer types. In the present study, naringenin and a Bcl-2 inhibitor, ABT-737, were used to investigate their combinative anticancer effect in the SGC7901 gastric cancer cell line. The results revealed that naringenin and ABT 737 were able to inhibit SGC7901 cell growth and colony formation, alone or in combination. Furthermore, the combination of these drugs was found to further increase the cleavage of caspase-3 and poly ADP-ribose polymerase. Naringenin and ABT-737 also decreased Akt activation and increased p53 expression, suggesting the involvement of these pathways in the inhibition of gastric cell growth. PMID- 26893667 TI - CORRIGENDUM. AB - [This corrects the article DOI: 10.3892/etm.2014.1581.]. PMID- 26893666 TI - Adjunctive corticosteroids for the treatment of Pneumocystis jiroveci pneumonia in patients with HIV: A meta-analysis. AB - The present study aimed to evaluate the effects of adjunctive corticosteroid treatment on Pneumocystis jiroveci pneumonia in patients with human immunodeficiency virus (HIV). A literature search of relevant randomized controlled trials (RCTs) published prior to March 2014 was performed using a number of websites, including PubMed, EMbase and Ovid, using the following keywords: Corticosteroids, glucocorticoide, cortisol, corticosterone, HIV/acquired immunodeficiency syndrome, P. jiroveci pneumonia, and PCP. All RCTs investigating the use of adjunctive corticosteroids for the treatment of P. jiroveci pneumonia in patients with HIV were evaluated in the present study. Stata 11.0 software was used to calculate the relative risk (RR) and 95% confidence interval (CI) following tests for consistency and potential biases. Six RCTs investigating a total of 548 patients were evaluated in the present meta analysis. The experimental groups (n=270) demonstrated a mortality rate of 15.2% (n=41); as compared with 27.7% (n=77) in the control groups (n=278). The present meta-analysis demonstrated that the RR and 95% CI were 0.55 and 0.35-0.85 (P<0.05), respectively, following treatment with adjunctive corticosteroids. This result indicated that patients in the experimental group had a 0.55 times reduced risk of mortality compared with the control group. Therefore, the results of the present meta-analysis demonstrated that the administration of adjunctive corticosteroids for the treatment of P. jiroveci pneumonia in patients with HIV may reduce the mortality rate of patients in the early phase of the disease. PMID- 26893665 TI - Protective effects of patchouli alcohol isolated from Pogostemon cablin on lipopolysaccharide-induced acute lung injury in mice. AB - Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Pogostemon cablin, which exerts anti-inflammatory, anti-influenza and cognitive-enhancing bioactivities. The present study aimed to investigate the protective effects of PA on acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) in mice. Dexamethasone was used as a positive drug for protection against LPS-induced ALI. The results of the present study demonstrated that pretreatment with PA significantly increased survival rate, attenuated histopathologic damage and lung edema, and decreased the protein content in the bronchoalveolar lavage fluid (BALF) of mice with ALI. Furthermore, PA significantly inhibited the expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the BALF, downregulated the levels of myeloperoxidase and malondialdehyde, and upregulated the activity levels of superoxide dismutase and glutathione peroxidase in lung tissue. These results indicated that PA may exert potent protective effects against LPS-induced ALI in mice, the mechanisms of which are possibly associated with the anti-inflammatory and antioxidative activities of PA. PMID- 26893668 TI - Diverse microRNAs with convergent functions regulate tumorigenesis. AB - MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-beta, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks. PMID- 26893669 TI - Primary Sjogren's syndrome initially presenting as submandibular mucosa associated lymphoid tissue lymphoma: A case report. AB - The present study reports the case of a 24-year-old female affected with primary Sjogren's syndrome (pSS), who presented with mucosa-associated lymphoid tissue (MALT) lymphoma of the submandibular gland. Reports of such cases, particularly in young patients, are very rare. The patient, who presented no oral or ocular symptoms prior to the development of the mass, underwent surgical ablation of the gland, and MALT lymphoma was diagnosed by histopathology. Since MALT lymphoma in the submandibular gland is rarely observed in otherwise healthy young females, a rheumatologist and an oncologist were consulted. Following a number of immunological tests, the results of the Schirmer's and Saxon tests were negative. However, the antinuclear antibody test revealed a speckled appearance, and there was also strong positivity for the serological markers of Sjogren's syndrome. Consequently, pSS was diagnosed, despite the fact that the patient did not fulfill all the diagnostic criteria for the disease. Therefore, MALT lymphoma in a single salivary gland should be used as a differential diagnosis for Sjogren's syndrome in young asymptomatic patients. Additionally, a multidisciplinary team is required for the treatment and management of these patients. PMID- 26893670 TI - Interleukin-6 as a potential molecular target in esophageal squamous cell carcinoma. AB - Knowledge of potential tumor markers may improve chemotherapeutic efficacy. Interleukin-6 (IL-6) expression in local tumor tissues is associated with cancer progression and poor prognosis in variety of cancer types. The aim of the present study was to investigate the role and potential application of IL-6 in determining the prognosis of esophageal carcinoma. KYSE170 and TE13 esophageal cancer cell lines were used to conduct cell- and animal-based experiments investigating biological changes and tumor behavior. Immunohistochemical analysis revealed that 70-80% of cancer cells exhibited positive staining for IL-6, compared with <15% of non-malignant epithelial cells. These immunohistochemical results were consistent with the mRNA expression levels detetced. The IL-6 silencing vector significantly reduced invasion and proliferation of the two cell lines and attenuated tumor growth in xenograft mouse models (P<0.05). The IL-6 silencing vector markedly reduced the presence of Ki-67 (a typical proliferation marker) and microvessel density, indicating that downregulation of IL-6 levels may greatly affect tumor growth and inhibition. The IL-6 silencing vector increased E-cadherin and matrix metalloproteinase (MMP)-9 expression levels in the two esophageal carcinoma cell lines. This vector also regulated the release of IL-6 in cell supernatant and serum in KYSE170- and TE13-tumor-bearing mice. The secretion of vascular endothelial growth factor and cluster of differentiation 31 (a nuclear protein) immunoreactive molecules were also reduced by the IL-6 silencing vector. Therefore, IL-6 may be an important trigger in the progression of angiogenesis and endothelial tube formation within the tumor, and targeting IL-6 may be a promising strategy for the treatment of esophageal cancer. PMID- 26893671 TI - Correlation of FOXC1 protein with clinicopathological features in serous ovarian tumors. AB - Transcriptional factor FOXC1 has been demonstrated to play a key role in embryogenesis in animal studies and may participate in tumorigenesis. However, the specific function of this gene in ovarian tumors has not been fully determined. In this study, potential correlations between FOXC1 expression and clinicopathological features of serous ovarian tumors were investigated. FOXC1 expression was analyzed in SKOV-3 and HO-8910 cell lines and serous ovarian tumor tissues. A significant correlation was observed between FOXC1 protein expression and pathological subtype as well as FIGO stage (P<0.05) in serous ovarian tumors in our retrospective study. No significant association was revealed between FOXC1 protein expression and the clinicopathological factors of age, histological grade and volume of ascites (P>0.05). The results suggest that high expression of FOXC1 protein may serve as a marker for benign serous ovarian tumors and a suggest a trend towards good prognosis. PMID- 26893672 TI - Risk factors of atherosclerosis during systemic therapy targeting vascular endothelial growth factor. AB - The aim of the present study was to examine the changes in intima-media thickness (IMT) and myocardial perfusion in association with other laboratory risk factors for atherosclerosis in patients treated with therapy that targeted vascular endothelial growth factor (VEGF). IMT, myocardial perfusion and laboratory risk factors of atherosclerosis were studied in 58 patients with metastatic colorectal carcinoma or metastatic renal cell carcinoma prior to and at 3-monthly intervals during anti-VEGF treatment. Compared with the pretreatment IMT, the results indicated that the IMT was consistently increased during therapy in the two patient groups. Patient blood pressure and concentration of troponin T increased transiently. An increase in the concentration of high-density lipoprotein cholesterol and decrease in the concentrations of C-reactive protein and homocysteine were also observed. Novel myocardial ischemia was evident in individual patients. In conclusion, anti-VEGF therapy affects the laboratory risk factors of atherosclerosis and results in an acceleration of atherosclerosis, as demonstrated by increased IMT. PMID- 26893673 TI - miR-96 induces cisplatin chemoresistance in non-small cell lung cancer cells by downregulating SAMD9. AB - Cisplatin is effective as a single agent or in combination with other drugs for the treatment of non-small cell lung cancer (NSCLC). A concerning clinical challenge with cisplatin-based NSCLC chemotherapy is the intrinsic and acquired chemoresistance to cisplatin. The sterile alpha motif domain-containing (SAMD9) gene has been reported as a potent tumor suppressor gene that inhibits tumorigenesis and progression of NSCLC. microRNAs (miRNA) have been revealed to play important roles in the regulation of cancer chemoresistance. To the best of our knowledge the present study explored the role of miRNA/SAMD9 signaling in regulating cisplatin chemoresistance in NSCLC for the first time. Out of the several candidate miRNAs predicted to bind the 3'-untranslated region (UTR) of the SAMD9 gene, miRNA-96 (miR-96) demonstrated significant target-sequence specific inhibition of the SAMD9 3'-UTR luciferase reporter activity in NSCLC cells. In addition, while NSCLC tumor samples exhibited significantly higher expression levels of miR-96 compared with adjacent normal tissues, the expression levels of SAMD9 were significantly lower than those in adjacent normal tissues. miR-96 and SAMD9 were overexpressed and knocked down in the human NSCLC H358 and H23 cell lines and the half maximal inhibitory concentration (IC50) of cisplatin and cell apoptosis rate under cisplatin treatment were used as measures of cisplatin chemoresistance. The present results identified that overexpression of miR-96 in NSCLC cells markedly decreased SAMD9 expression and cisplatin-induced apoptosis, and increased the cisplatin IC50, which could be eliminated by overexpression of SAMD9. By contrast, knocking down miR-96 in NSCLC cells using antagomir-96 significantly increased SAMD9 expression and the cisplatin-induced apoptosis and decreased cisplatin IC50, which could be completely reversed by a knockdown of SAMD9. In conclusion, the current study demonstrates that miR-96 targets and downregulates SAMD9 in NSCLC, which decreases cisplatin-induced apoptosis and induces cisplatin chemoresistance in NSCLC cells. The findings of the present study add novel insights into the function of miR-96 and SAMD9 in cancer, as well as into the molecular mechanisms underlying NSCLC chemoresistance. PMID- 26893674 TI - Revealing the role of VEGFA in clear cell sarcoma of the kidney by protein protein interaction network and significant pathway analysis. AB - Despite clear cell sarcoma of the kidney (CCSK) being the second most common renal tumor in children, its mechanism has not yet been fully investigated. The aim of the present study was to investigate the potential role of vascular endothelial growth factor A (VEGFA) in CCSK development. Following preprocessing of the original GSE2712 data, the differentially-expressed genes (DEGs) between 14 CCSK and 3 fetal kidney samples were identified through Significance Analysis of Microarrays, using the R package. Pathway enrichment analysis was then performed on the DEGs. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and the DEGs that were enriched in the most significant pathways. Following this, gene ontology analysis was performed on the VEGFA-associated genes, whilst transcription factor binding site analysis was conducted on the hot genes. A total of 2,681 DEGs, including 543 upregulated and 2,138 downregulated genes, were identified, and these were significantly enriched in pathways associated with cancer and focal adhesion. Furthermore, VEGFA, integrin beta1, integrin alphaV, v-akt murine thymoma viral oncogene homolog 1 and endothelial growth factor receptor were identified as hot genes in the PPI network. In addition, the upregulated VEGFA-associated genes, cyclin D1 and cyclin-dependent kinase inhibitor 1B, affected kinase regulation, and the downregulated VEGFA associated genes, receptor tyrosine-protein kinase erbB-2, mesenchymal-epithelial transition tyrosine kinase receptor and kinase insert domain receptor, were enriched in the protein tyrosine kinase process. It was identified that VEGFA was regulated by restorer of fertility, erythromycin resistance methylase, GA binding protein subunit alpha, norepinephrine transporter, nuclear factor kappaB and Sp2 transcription factor genes. Overall, VEGFA and its associated genes serve important roles during CCSK development, and alongside transcription factors, they may function as novel therapeutic targets for disease treatment. PMID- 26893675 TI - A comparative dosimetric study of volumetric-modulated arc therapy vs. fixed field intensity-modulated radiotherapy in postoperative irradiation of stage IB IIA high-risk cervical cancer. AB - The aim of the present study was to compare the dosimetry features of volumetric modulated arc therapy (VMAT) and fixed field intensity-modulated radiotherapy (f IMRT) in postoperative irradiation of stage IB-IIA high-risk cervical cancer. Fifteen patients exhibiting stage IB-IIA high-risk cervical cancer, who had been treated with postoperative adjuvant concurrent radiochemotherapy, were selected. The clinical target volume (CTV) and organs at risk (OARs) were delineated according to contrast computed tomography images. The planning target volume (PTV) was subsequently produced by using 1 cm uniform expansion of the CTV. The treatment plans were intended to deliver 50 Gy in 25 fractions. The OARs that were contoured included the bladder, rectum, small bowel and femoral heads. Dose volume histograms were used to evaluate the dose distribution in the PTV and OARs. VMAT and f-IMRT treatment plans resulted in similar dose coverage of the PTV. VMAT was superior to f-IMRT in conformity (P<0.05), and resulted in a reduction of OARs irradiated at high dose levels (V40 and V50) compared with f IMRT (P<0.05), particularly for the bladder. However, the doses of low levels (V10 and V20) delivered to OARs with f-IMRT were slightly reduced compared with VMAT (P<0.05). For ambilateral femoral heads, VMAT demonstrated improved sparing compared with f-IMRT, with regard to D5 (P<0.05). Furthermore, VMAT treatment plans revealed a significant reduction in monitor units (MU) and treatment time. VMAT techniques exhibited similar PTV coverage compared with f-IMRT. At doses of high levels delivered to OARs, VMAT demonstrated improved sparing compared with f IMRT, particularly for the bladder, while significantly reducing treatment time and MU number. PMID- 26893676 TI - Assessment of radioiodine therapy efficacy for treatment of differentiated thyroid cancer patients with pulmonary metastasis undetected by chest computed tomography. AB - Radioiodine therapy (RAI) has proven effective for the treatment of patients exhibiting differentiated thyroid cancer (DTC) with pulmonary metastases. However, the early detection of metastasis remains challenging, and various studies have reported variations in radioiodine treatment efficacy. The present study investigated whether RAI is an effective method for the treatment of DTC with pulmonary metastases undetected by computed tomography (CT). A retrospective study was performed, analyzing iodine-131 (131I) therapy in 21 DTC patients with lung metastases that were undetected by CT. All 21 patients were initially treated with radioiodine ablation of thyroid remnants. Routine chest CT was performed prior to 131I treatment without diagnostic radioiodine whole-body scanning (DxWBS), and post-therapeutic WBS was performed 3-5 days subsequent to oral administration of 131I. The overall effectiveness rate was 95.2% (20/21). The rates for complete response (CR), partial response and no response were 23.8 (5/21), 71.4 (15/21) and 4.8% (1/21), respectively. There were 12 patients with diffuse uptake, and the remaining 9 patients demonstrated focused and low uptake. The difference in CR rate between diffuse uptake and focused uptake patients was not statistically significant (P=0.123). A correlation was observed between thyroglobulin (Tg) levels and extrapulmonary metastases. All patients exhibited extrapulmonary metastases when Tg levels were >87.5 ng/ml (area under receiver operating characteristic curve, 1.0; P<0.001). Overall, DTC patients with lung metastases undetected by CT imaging responded well to 131I radiotherapy and demonstrated a positive prognosis. Serum Tg levels prior to 131I treatment may correlate with metastasis, and this may suggest a requirement for the performance of DxWBS prior to radiotherapy. PMID- 26893677 TI - Primary gastric natural killer/T-cell lymphoma with diffuse CD30 expression and without CD56 expression: A case report. AB - The majority of natural killer (NK)/T-cell lymphomas occur in the nasal cavity and rarely involve the stomach. They possess a specific immunophenotype, with the expression of cluster of differentiation (CD)56, CD2 and CD3epsilon, but without CD3 expression. Few cases of NK/T-cell lymphoma have partial CD30 expression. The present study reveals a unique case of a 41-year-old female patient with gastric NK/T-cell lymphoma that did not express CD56 and diffusely expressed CD30. Immunohistochemical staining demonstrated that the tumor cells expressed CD3epsilon, CD43, CD30 and granzyme B and did not express CD2, CD4, CD5, CD7, CD8, CD56, anaplastic lymphoma kinase, CD20, paired box-5 or pan cytokeratin. Based on the immunostaining profile and morphological features, the initial diagnosis considered was gastric anaplastic large cell lymphoma. However, following a consultation with other pathologists, the Epstein-Barr virus (EBV) status of the patient was investigated to exclude a diagnosis of NK/T-cell lymphoma. Notably, the signal for EBV RNA was diffuse positive. Therefore, the final diagnosis was corrected to NK/T-cell lymphoma. To the best of our knowledge, the present study is the first to report NK/T-cell lymphoma in the stomach with a diffuse CD30-positive and CD56-negative phenotype. PMID- 26893678 TI - Study on chemotherapeutic sensitizing effect of nimotuzumab on different human esophageal squamous carcinoma cells. AB - Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5 fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P<0.05), but not statistically significant for EC9706 (P>0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P<0.05), but not on in the EC1 chemotherapy group (P>0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1 or EC9706 cells. The cell killing effect of the combined use of h-R3 with DDP and 5-FU showed no obvious synergistic effect compared to the single-drug group, but only an additive effect. PMID- 26893679 TI - Expression of pY397 FAK promotes the development of non-small cell lung cancer. AB - Focal adhesion kinase (FAK) expression has been identified as associated with cancer development and metastasis. Autophosphorylation of FAK at tyrosine (Y) 397 (pY397) performs a critical role in tumor cell signaling. However, few studies have evaluated the expression of pY397 FAK in non-small cell lung cancer (NSCLC). In the present study, pY397 FAK expression in NSCLC was investigated using immunohistochemistry. pY397 FAK staining scores were compared between various groups of specimens and the associations between clinical and pathological characteristics were investigated. A Kaplan-Meier survival curve was used to determine the association between pY397 FAK expression and the prognosis of NSCLC patients. The results of the present study revealed that pY397 FAK expression was localized to the cytoplasm of lung cells, and that pY397 FAK was overexpressed in NSCLC tissues, as well as associated metastatic tissues, when compared with the corresponding non-tumor tissues. However, no significant difference was identified between the pY397 FAK expression in primary lesions and lymph node metastases. Furthermore, pY397 FAK staining scores were not found to be associated with the tumor size, gender, degree of differentiation, histotypes, presence of lymph node metastases or survival rate of NSCLC patients. These results indicate that pY397 FAK is involved with the development of NSCLC, but is not a prognostic marker for the disease. PMID- 26893680 TI - Role of BCL2-associated athanogene in resistance to platinum-based chemotherapy in non-small-cell lung cancer. AB - The present study aimed to address the pharmacogenetic role of BAG1 in platinum based chemotherapy in advanced non-small-cell lung cancer (NSCLC) and in cultured human lung adenocarcinoma A549 cells. A total of 108 NSCLC patients (stages I IIIA) were treated with a standard chemotherapy regimen of cisplatin plus vinorelbine. Additionally, in vitro cultured A549 cells were treated with cisplatin in the presence or absence of tunicamycin. Cell proliferation was determined by MTT assay and protein levels were assessed via western blot analysis. Patients with BAG1-positive expression were revealed to have a prolonged survival time (progression-free survival, 24.0 months) compared with that of patients without BAG1 expression (21.6 months; chi2=18.018, P<0.05). Treatment of A549 cells with tunicamycin followed by cisplatin resulted in elevated BAG1 levels. In addition, tunicamycin was found to significantly enhance cisplatin-induced growth inhibition and apoptosis in A549 cells. The results indicate that BAG1 is important in cisplatin-induced cell death in lung adenocarcinoma, suggesting that endoplasmic reticulum stress may promote the sensitivity of NSCLC patients to chemotherapy. PMID- 26893681 TI - Resistance to the c-Met inhibitor KRC-108 induces the epithelial transition of gastric cancer cells. AB - Investigation of the mechanisms of resistance to targeted therapies is essential as resistance acquired during treatment may lead to relapse or refractoriness to the therapy. Our previous study identified the small molecule KRC-108 as a result of efforts to find an anticancer agent with c-Met-inhibitory activity. In the present study, the changes accompanying resistance to KRC-108 were investigated in the gastric cancer cell line MKN-45 and its KRC-108-resistant clones by western blot and immunofluorescence analyses. Increased expression of the c-Met protein was observed in KRC-108-resistant cells compared with that of the parental cells, and the phosphorylation of c-Met also increased in cell lines resistant to KRC-108. Resistance to the c-Met inhibitor was associated with cell morphological changes: MKN-45 parental cells, which had a round and poorly differentiated morphology, were altered to exhibit an epithelial cell-like phenotype in KRC-108-resistant clones. Consistent with the transition to an epithelial morphology, the expression of E-cadherin was increased in resistant cells. Using immunoprecipitation, an interaction between E-cadherin and the c-Met protein was observed in the KRC-108-resistant cells. Immunohistochemical analysis of human gastric carcinoma tissues revealed the co-expression of E-cadherin and c Met. These results suggest that the epithelial transition in KRC-108-resistant cells is mediated by recruiting E-cadherin to c-Met protein. Thus, the present study identified a mechanism used by cancer cells to confer resistance to anticancer agents. PMID- 26893682 TI - Myoferlin expression in non-small cell lung cancer: Prognostic role and correlation with VEGFR-2 expression. AB - Myoferlin is a protein that is associated with cellular repair following injury. The expression of myoferlin in breast cancer and pancreatic adenocarcinoma has been reported to correlate with tumor invasiveness, epithelial to mesenchymal transition and an adverse prognosis. In the present study, myoferlin expression was investigated in non-small cell lung carcinoma (NSCLC), along with its association with patient prognosis and the expression of a number of other proteins. A total of 148 patients exhibiting NSCLC were enrolled in the present study. The survival data of all patients was examined, and myoferlin, vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor, E-cadherin, beta-catenin, thyroid transcription factor-1 and tumor protein p63 expression was investigated via immunohistochemical staining of tissue microarrays. Myoferlin expression was detected in the cytoplasm of 75/148 (50.7%) of the NSCLC cases. In the adenocarcinoma cases, myoferlin-positive patients possessed a poorer prognosis (odds ratio, 2.94; P=0.339). In the squamous cell carcinoma cases, myoferlin expression was significantly associated with VEGFR-2 expression (P=0.001). Immunohistochemical staining for VEGFR-2 and myoferlin expression indicated similar features and cytoplasmic staining in tumor cells. As VEGFR-2 is a significant target for novel anticancer therapies, it is anticipated that myoferlin may also possess the potential to become a novel clinical target for the treatment of NSCLC. PMID- 26893683 TI - Genomic mapping of pathways in endometrial adenocarcinoma and a gastrointestinal stromal tumor located in Meckel's diverticulum. AB - The present study reports the case of a 71-year-old female patient diagnosed with endometrial adenocarcinoma, which was confirmed by histopathology. In the course of performing an elective hysterectomy with adnexa removal, a solid tumor located in Meckel's diverticulum (MD) was identified and excised. Due to the unique nature of the lesion, the tumor tissue underwent broad mapping of any genomic alterations once the histopathological examination was completed. The genetic testing was conducted using a high-resolution microarray and resulted in the identification of 45 genomic abnormalities, including 4 chromosomal aneuploidies. Within those regions, alterations of 87 known cancer genes were assigned. The involvement of v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog gene alteration was noted to be a key player for triggering gastrointestinal stromal tumor transformation for this unusual case. A total of 12 genes, showing mutual interaction in different cancer types or involved in diverse cellular processes, were identified. These reported data may shed light on the carcinogenesis of a rare MD tumor. PMID- 26893684 TI - Primary intratesticular rhabdomyosarcoma: A case report and literature review. AB - Rhabdomyosarcoma (RMS) that primarily occurs in the testes is particularly rare, with only retrospective studies and sporadic cases reported in the literature. The present study describes the case of a large, primary intratesticular RMS (ITRMS) that was treated with a radical inguinal orchiectomy (RIO) and a regimen of chemotherapy. The study also presents a review of the literature regarding primary ITRMSs, aiming to elucidate the clinical characteristics and optimal treatment of the disease. A 14-year-old male presented with a 1-year history of a slow-growing, painless, left scrotal mass. Magnetic resonance imaging identified a mass in the left scrotum with mixed signal intensity; no abnormal signals were identified in the right testicle and retroperitoneal lymph node. An X-ray of the chest demonstrated no evidence of metastasis. Subsequent to this, a left RIO was performed. Histopathological and immunohistochemical examination confirmed the final diagnosis of embryonal ITRMS. At 21 days post-surgery, an 18F fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan identified widespread metastatic lesions in the lungs, local lymph nodes and bones, presenting as increased glucose metabolism nodules. Subsequently, the patient received six sequential cycles of adjunct chemotherapy. The patient is alive with disease in October 2015. The case described is noteworthy as it is an example of ITRMS, in which the patient received successful treatment. However, multidisciplinary treatment may further improve the outcome of the disease. PMID- 26893685 TI - Correlation between the overexpression of Yin Yang 1 and the expression levels of miRNAs in Burkitt's lymphoma: A computational study. AB - A growing number of studies have highlighted the role of microRNAs (miRNAs or miRs) in the development and progression of cancer. In particular, the aberrant expression of cancer-related proteins, such as oncogenes and tumor suppressors has been shown to correlate with the modulation of the expression of specific miRNAs. In the present study, we aimed to determine which downregulated miRNAs may be involved in modulating the expression of the oncogenic transcription factor, Yin Yang 1 (YY1). YY1 has been reported to be overexpressed in several malignancies and our previous studies have highlighted the significant correlation between the levels of YY1 and aggressive behavior in non-Hodgkin's lymphoma (NHL). A total of 57 miRNAs that are potentially capable of targeting YY1 was identified through in silico approaches. The search of publicly available NHL datasets, including paired mRNA and miRNA data (GSE23026) highlighted a significant correlation (Pearson's correlation, r>0.5) between the expression levels of YY1 and the expression levels of a limited set of miRNAs, including miR 363, miR-200a, miR-23b, miR-15a and miR-15b. Intriguingly, both hsa-miR-363 and hsa-miR-200a belong to the top 20 miRNAs that were found to be downregulated in Burkitt's lymphoma (BL) tissue compared to normal tissue. Although further validation studies are warranted, the identification of these two miRNAs associated with the upregulation of YY1 in BL may provide further insight into the pathogenesis of this tumor and may contribute to more personalized and targeted treatment approaches for patients with this disease. PMID- 26893686 TI - Regulation and clinical significance of the hypoxia-induced expression of ANGPTL4 in gastric cancer. AB - Solid tumors are often exposed to hypoxia. Hypoxia inducible factor (HIF)-1alpha upregulates numerous target genes associated with the malignant behavior of hypoxic cancer cells. A member of the angiopoietin family, angiopoietin-like protein 4 (ANGPTL4) is a hypoxia-inducible gene. The present study aimed to clarify whether ANGPTL4 is regulated by HIF-1alpha in gastric cancer cells. The study also assessed whether ANGPTL4 expression is associated with clinicopathological factors or HIF-1alpha expression in gastric cancer tissues. Hypoxia-induced ANGPTL4 expression was quantitatively analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in 10 gastric cancer cell lines. RT-qPCR was further employed to investigate the HIF-1alpha dependency of ANGPTL4 expression using HIF-1alpha-knockdown transfectant 58As9-KD and control 58As9-SC gastric cancer cells. The HIF-1alpha and ANGPTL4 expression levels were immunohistochemically analyzed in 170 gastric cancer tissue specimens and were assessed for any correlations with the clinicopathological factors and/or patient survival. Subsequently, hypoxia-induced ANGPTL4 expression was observed in 7 out of 10 gastric cancer cell lines. The hypoxic induction of ANGPTL4 was almost preserved in the 58As9-KD cells compared with that observed in the 58As9-SC cells, while the induction of known HIF-1alpha target gene, carbonic anhydrase 9, was completely suppressed in the 58As9-KD cells. In the gastric cancer tissues, ANGPTL4 expression was inversely correlated with the tumor depth, whereas HIF-1alpha expression was positively correlated with venous invasion. A survival analysis revealed that the expression of ANGPTL4 was significantly correlated with a longer survival time, whereas that of HIF-1alpha was correlated with a shorter survival time. In conclusion, the present findings indicate that hypoxia-induced ANGPTL4 expression is independent of HIF-1alpha in hypoxic gastric cancer cells. ANGPTL4 may be a favorable marker for predicting a long survival time, whereas HIF-1alpha predicts a poor prognosis, in gastric cancer patients. The hypoxic environment independently induces ANGPTL4 and HIF-1alpha, which are believed to exhibit adverse effects on tumor progression. PMID- 26893687 TI - Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment. AB - The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB 231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation. PMID- 26893689 TI - Apelin-13 induces autophagy in hepatoma HepG2 cells through ERK1/2 signaling pathway-dependent upregulation of Beclin1. AB - The aim of the present study was to investigate the effect of Apelin-13 on autophagy in hepatocellular carcinoma HepG2 cells and the underlying mechanism of the effect. The HepG2 cells were treated with Apelin-13 at a final concentration of 0.0001, 0.001, 0.01 and 0.1 umol/l for 24 h. Cells were also treated with 10 umol/l PD98059 for 24 h. The expression of the extracellular signal-regulated kinase (ERK)1/2, phosphorylated ERK1/2 (pERK1/2) and Beclin1 proteins were detected by western blot analysis. Beclin1 mRNA expression was also detected by reverse transcription-polymerase chain reaction. Autophagy was observed using fluorescence microscopy subsequent to monodansylcadaverine (MDC) staining. Following treatment with the various concentrations of Apelin-13, the expression of the ERK1/2 protein remained at a similar level, whereas the expression of pERK1/2 increased in a dose-dependent manner. Compared with the control group, the increase was significant (P<0.05). Similarly, Beclin1 expression was upregulated at the protein and mRNA levels by Apelin-13 treatment in a dose dependent manner and was significantly increased compared with the control group. However, following treatment with the Apelin-13 inhibitor PD98059, the expression of pERK1/2, Beclin1 protein and Beclin1 mRNA were significantly decreased (P<0.05). In addition, Apelin-13 induced the autophagy of HepG2 cells in a dose dependent manner, as revealed by MDC staining. PD98059 inhibited autophagy of HepG2 cells induced by Apelin-13. Therefore, Apelin-13 may promote autophagy in HepG2 cells by inducing the phosphorylation of ERK1/2 and upregulating the expression of Beclin1. PMID- 26893688 TI - Interleukin-8: A potent promoter of angiogenesis in gastric cancer. AB - Angiogenesis is a critical process in the development of tumor malignancy and occurs at various stages of tumor progression. Interleukin-8 (IL-8) is a pro angiogenic factor produced by tumor-infiltrating macrophages that has been revealed to facilitate the development of angiogenesis in various cancers. However, whether IL-8 activates angiogenesis in gastric cancer remains unclear. The present study investigated the effect of IL-8 on the migration and canalization capacities of human umbilical vein endothelial cells (HUVECs). In addition, the protein and messenger RNA (mRNA) expression of selected angiogenesis markers, consisting of vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)-1 and VEGFR-2, were assessed in the HUVECs. The HUVECs were co-cultured with human gastric cancer SGC7901 cells and exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1.0 ng/ml). The migration and canalization abilities of the cells were detected by Transwell chamber and tube formation assays. Protein expression was detected using immunofluorescence and western blot analysis, and mRNA levels were assessed using reverse transcription quantitative polymerase chain reaction. The protein and mRNA levels of VEGF-A, VEGFR-1 and VEGFR-2 were measured in HUVECs cultured for 24 h. IL-8 at concentrations of 0.5, 0.8 and 1.0 ng/ml significantly promoted HUVEC cell migration (P=0.005, P=0.001 and P<0.001, respectively) and tube formation (P=0.039, P=0.003 and P<0.001, respectively). IL-8 at concentrations of 0.2, 0.5, 0.8 and 1.0 ng/ml significantly elevated the protein levels of VEGF-A (P<0.001) and VEGFR-2 (P=0.034, P<0.001, P<0.001 and P<0.001, respectively). IL-8 at concentrations of 0.8 and 1.0 ng/ml significantly elevated the protein levels of VEGF-1 (P=0.037 and P=0.002, respectively). Similarly, IL-8 at concentrations of 0.5, 0.8 and 1.0 ng/ml significantly upregulated the mRNA levels of VEGF-A (P=0.046, P=0.001 and P<0.001, respectively) and VEGFR-1 (P=0.042, P<0.001 and P<0.001, respectively). IL-8 at concentrations of 0.2, 0.5, 0.8 and 1.0 ng/ml significantly upregulated the mRNA levels of VEGFR-2 (P=0.003, P=0.005, P<0.001 and P<0.001, respectively). In conclusion, IL-8 may be a potent promoter of angiogenesis in gastric cancer. PMID- 26893691 TI - Cerebellar liponeurocytoma: A case report and review of the literature. AB - Cerebellar liponeurocytoma is rare, and the clinical characteristics and treatment strategy remain unclear. In the present study, a case of cerebellar liponeurocytoma was retrospectively reported and a literature review was performed. A 45-year-old female presented due to occipital headaches, exhibiting a hoarse voice and a broad-based gait. Pre-operative magnetic resonance images revealed a lesion occupying the right hemisphere of the cerebellum and the inferior vermis, compressing the medulla oblongata from the right side, and extending through the foramen magnum to the C2 level. A total resection was performed, and pathological analysis of the lesion showed positivity for synaptophysin, S-100 and neuronal nuclear antigen, partial positivity for Olig-2, and negativity for glial fibrillary acidic protein and epithelial membrane antigen. In addition, the Ki-67 index was low (<5%). Thus, a diagnosis of cerebellar liponeurocytoma was determined. Total resection was successful and the patient was followed up closely. A review of the literature showed that cerebellar liponeurocytoma is mainly located in the cerebellum, with rare extra cerebellar cases. Certain studies have suggested that the tumor may be located supratentorially and subtentorially, and should be renamed as solely liponeurocytoma. Total resection of the tumor contributes to an improved prognosis, while a subtotal resection and high Ki-67 index lead to recurrence. The tumor is similar to a tumor of low malignancy, with long-term recurrence. Radiation is recommended when there is residual tumor, recurrence or when the Ki 67 is high. PMID- 26893690 TI - Intracranial solitary fibrous tumors: A report of two cases and a review of the literature. AB - Solitary fibrous tumors (SFTs) are uncommon, with the pleura as a site of predilection. Central nervous system SFTs, particularly intracranial SFTs, are extremely rare. The lesions are generally benign and localized, and surgery is the main therapeutic solution. The current study reports the cases of a patient who presented with right haunch pain, right leg weakness and paresthesias for several months, and a patient with a history of unexpected loss of consciousness. Magnetic resonance imaging revealed the presence of lesions, with a spindle cell morphology evident on pathological examination. The immunohistochemical examination demonstrated a strong immunoreaction for cluster of differentiation 34, which supported the diagnosis of an SFT. Following a near-total resection, the patients had a good neural prognosis. The present study also provides a literature review, discussing the imageological and pathological characteristics of SFT, and the diagnostic methods that aid in distinguishing the entity from other spindle-cell central nervous system tumors. PMID- 26893692 TI - Ectopic congenital bronchogenic cyst accompanied by infection appearing in the cervical region of an elderly female patient: A case report. AB - Bronchogenic cysts (BCs) are rare congenital cystic lesions arising as a development malformation in the trachea-bronchial system during the embryonic period. The cysts mostly occur in the mediastinum, with an extremely low morbidity rate in the oromaxillofacial-head and neck region. The age distribution of patients who present with BCs shows a significant predominance towards young individuals compared with the elderly. The current study reports the case a 70 year-old female who presented with a painful mass in the right cervical region. Pre-operative computed tomography (CT) and ultrasound showed a heterogeneous hypodense cystic lesion accompanied by infection. A mass of gaseous density was observed on repeat CT following antibiotic therapy. The pathological examination after complete resection revealed a BC, which can also be easily misdiagnosed as common congenital cervical cysts, such as a branchial cleft cyst or a thyroglossal duct cyst, among others. There was no recurrence or any discomfort during the 34-month follow-up period. PMID- 26893693 TI - Complete response of giant desmoplastic small round cell tumor treated with chemoradiotherapy: A case report. AB - Desmoplastic small round cell tumor (DSRCT) is a rare tumor that mainly affects adolescents, and typically involves the abdominal and pelvic peritoneum. The present study reports one case of giant DSRCT, treated with concurrent chemoradiotherapy, and reviews the available medical literature. A 38-year-old man presented with a 3-month history of pain in the left lower abdomen and nausea, associated with decreased appetite and weight loss. Computed tomography (CT) showed a 12.3*7.9 cm confluent solid mass in the lower abdomen and pelvic cavity. The patient underwent exploratory laparotomy and the final pathological diagnosis was DSRCT. Following laparotomy, the patient was treated with external beam radiotherapy to the whole abdomen and pelvis to a dose of 40 Gy plus a 20 Gy boost to the residual disease. The results indicated that synchronous chemotherapy with cyclophosphamide, adriamycin and cisplatin combined with radiotherapy significantly improved locoregional control of DSRCT and a complete response, as measured by CT assessment 2 months subsequent to radiotherapy. In conclusion, DSRCT is a rare malignancy requiring multidisciplinary treatment, including surgery, chemotherapy and radiotherapy. The results of the present study confirm that radiotherapy has a significant role in the treatment of advanced abdominal DSRCT and may contribute to durable remission. PMID- 26893694 TI - Malignant intrasellar meningioma presenting as an invasive pituitary macroadenoma: A rare case report and literature review. AB - Intrasellar meningiomas are rare tumors that have the ability to mimic non functioning pituitary adenomas. The majority of meningiomas are slow-growing and benign, therefore an intrasellar meningioma with malignant histological features is extremely rare. The present study describes the case of a malignant diaphragm meningioma that was controlled through combined chemotherapy, following subtotal surgical resection. The patient's symptoms ceased and no tumor recurrence was detected at the 3-year follow-up. Hormone levels were also observed as normal. Further investigation of similar cases may aid in achieving an accurate pre operative diagnosis. This would prove particularly beneficial in regards to intrasellar meningiomas due to their specific location and surgical treatment. The present study analyzes the requirement of chemotherapy for the treatment of these unique tumors. PMID- 26893695 TI - Hepatoid adenocarcinoma of the stomach: A case report of a rare type of gastric cancer. AB - Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer with an extremely poor prognosis. The current study reports a rare case of HAS, characterized by gastric cancer and infiltration of cancer cells into the left liver lobe, as well as lymphadenectasis. The expression of alpha-fetoprotein (AFP) was markedly increased in the tumor cells of the liver neoplasms. A gastric biopsy indicated highly, moderately and poorly differentiated papillary adenocarcinoma. The patient underwent two cycles of chemotherapy with oxaliplatin (130 mg; day 1) and capecitabine (2 mg, twice daily; days 1-14). At 7 weeks after the chemotherapy, an expanded gastrectomy and radical resection of left lung lobe were performed on the operable lesion. AFP expression was significantly decreased following the procedure. A literature review was also conducted by searching PubMed/Medline, indicating that surgery and chemotherapy may positively affect the outcomes of HAS patients. PMID- 26893696 TI - MicroRNA-497 regulates cell proliferation in hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. MicroRNA-497 (miR-497) is known to be downregulated in several types of human cancer; however, the expression, function and underlying mechanisms of miR-497 in HCC remain unclear. Therefore, the present study investigated miR-497 expression in HCC samples and HCC-derived cell lines using reverse transcription quantitative polymerase chain reaction. The protein expression of one of the predicted common targets of miR-497, insulin-like growth factor-1 receptor (IGF 1R), was assessed using western blot analyses and immunohistochemistry. The role of miR-497 in regulating the proliferation of HCC-derived cells was also investigated in vitro and in vivo. Of 60 paired specimens from HCC patients, miR 497 was downregulated in 42 cancer specimens compared with adjacent non-cancer tissues. Western blotting and immunohistochemical analyses revealed that IGF-1R expression was significantly increased in HCC compared to control tissues. In addition, overexpression of miR-497 was observed to inhibit colony formation and tumor growth in MHCC-97H human HCC cells. Conversely, SMMC-7721 human HCC cells transfected with a miR-497 inhibitor exhibited enhanced colony formation and tumor growth. Finally, IGF-1R protein, phosphoinositide 3-kinase/Akt signaling pathway-associated proteins and cyclin pathway-associated proteins were differentially expressed between miR-497-overexpressing cells and miR-497 silenced cells. These results indicate that miR-497 may be a potentially effective gene therapy target. PMID- 26893697 TI - Mesenchymal stem cells promote tumor angiogenesis via the action of transforming growth factor beta1. AB - Mesenchymal stem cells (MSCs) may influence the growth and metastasis of various human malignancies, including hepatocellular carcinoma (HCC). Therefore, the underlying mechanisms via which MSCs are able to affect malignancies require investigation. In the present study, the potential role of MSC in the angiogenesis of HCC was investigated. A total of 17 nude mouse models exhibiting human HCC were used to evaluate the effects of MSC on angiogenesis. A total of 8 mice were injected with human MSCs via the tail vein, and the remaining 9 mice were injected with phosphate-buffered saline as a control. A total of 35 days subsequent to the injection of MSCs, the microvessel density (MVD) of tumors was evaluated by immunostaining, using cluster of differentiation 31 antibody. The mRNA levels of transforming growth factor (TGF)beta1, Smad2 and Smad7 were detected using reverse transcription-quantitative polymerase chain reaction. Protein expression levels of TGFbeta1 and vascular endothelial growth factor (VEGF) in tumor tissues were analyzed using ELISA. Compared with controls, MVD in MSC-treated mice was significantly increased (28.00+/-9.19 vs. 18.11+/-3.30; P=0.006). The levels of TGFbeta1 mRNA in the MSC-treated group were 2.15-fold higher compared with the control group (1.27+/-0.61 vs. 0.59+/-0.39; P=0.033), and MVD was higher in the group exhibiting increased TGFbeta1 mRNA levels compared with the control group (26.50+/-9.11 vs. 19.44+/-6.14; P=0.038). In addition, a close correlation between the expression levels of TGFbeta1 and VEGF was identified. The results of the present study suggested that MSCs may be capable of enhancing the angiogenesis of HCC, which may be partly due to the involvement of TGFbeta1. PMID- 26893698 TI - Primary localized amyloidoma of the renal pelvis: A case report and literature review. AB - Primary localized amyloidomas of the renal pelvis are challenging to diagnose, due to non-specific imaging results and the unusual location. The present study reports a rare case of primary localized amyloidoma of the renal pelvis and aims to illustrate the challenges in pre-operatively discriminating between this disease and transitional cell carcinomas. The present study identified that the mass was situated in the left renal pelvis using ultrasonography. A nephroureterectomy was performed following careful preparation. Finally, histopathological studies revealed that the tumor consisted of massive diffuse deposits of amyloid and microscopic amorphous eosinophilic material, which stained positively for Congo red, demonstrating potassium permanganate digestion. Consequently, a diagnosis of amyloid light chain-type amyloidoma was determined. Systematic examinations were performed following the unexpected diagnosis, which eliminated the possibility of amyloid associated-type amyloidoma. In total, 4 months post-surgery, the patient remained tumor-free. PMID- 26893699 TI - Prolonged complete response following gemcitabine-erlotinib combined therapy in advanced pancreatic cancer. AB - Pancreatic cancer is one of the most lethal types of malignant solid tumor and is typically associated with a poor prognosis. The majority of patients are diagnosed with advanced-stage disease, therefore, the median survival period is <6 months. Recently, a number of basic research projects and clinical trials were undertaken with the aim of improving treatment outcomes in pancreatic cancer; however, only one agent, erlotinib, passed the clinical trials. Erlotinib is an inhibitor of epidermal growth factor receptor, which when overexpressed in cancer, promotes angiogenesis, cell proliferation and inhibits apoptosis. The US Food and Drug Administration and European Medicines Agency approved erlotinib in combination with gemcitabine for the first-line treatment of advanced pancreatic cancer. To the best of our knowledge, the current study is the first to report a case of pancreatic cancer treated with this regimen alone to achieve a complete response (CR). A 40-year-old male with a medical history of chronic pancreatitis and hypertension was diagnosed with medically inoperable adenocarcinoma of the pancreas. Following palliative surgery, the patient began palliative gemcitabine and erlotinib chemotherapy. After three months, this treatment strategy resulted in a CR, as determined by imaging studies. Therapy was discontinued after 14 months due to the development of peritoneal metastases and the patient was referred for treatment with the folinic acid, 5-fluorouracil, irinotecan and oxaliplatin regimen. A CR is rarely reported in pancreatic cancer, however, a treatment strategy of gemcitabine and erlotinib may induce rapid regression of advanced-stage disease. PMID- 26893700 TI - MicroRNA-205 increases the sensitivity of docetaxel in breast cancer. AB - Chemotherapy has been widely used in breast cancer therapy, but the efficacy of chemotherapy is intimately associated with the sensitivity of therapeutic drugs to breast cancer. Docetaxel is a first-line chemotherapeutic drug in breast cancer treatment, but further improvement to its efficacy has thus far proved difficult. microRNAs (miRs) are a class of endogenous, small, non-coding RNAs, which regulate gene expression at the post-transcriptional level. miR-205, a regulator of HER-3, is reported to be a tumor suppressor in breast cancer. In the present study, the reintroduction of miR-205 is shown to inhibit cell proliferation and clonogenic potential, and increase the sensitivity of MCF-7 and MDA-MB-231 cells to docetaxel. miR-205 also shows a synergistic effect with docetaxel in vivo. The present study provides a novel strategy to increase the sensitivity to docetaxel in breast cancer patients. PMID- 26893701 TI - Large moderately-differentiated ovarian Sertoli-Leydig cell tumor in a 13-year old female: A case report. AB - Sertoli-Leydig cell tumor of the ovary, also known as androblastoma, is a rare neoplasm from the group of sex cord-stromal tumors of the ovary. The tumor accounts for <0.5% of all primary ovarian neoplasms. The clinical signs and symptoms of Sertoli-Leydig cell tumors can be associated with either hormonal production or the presence of a mass-occupying lesion. In the current study, a 13 year-old female was diagnosed with a stage Ic ovarian Sertoli-Leydig cell tumor following abdominal pain and distension. One month after a right oophorectomy, the follow-up magnetic resonance imaging scan was negative for residual or recurrent tumor. The overall 5-year survival rate for moderately-differentiated (grade 2) and poorly-differentiated (grade 3) Sertoli-Leydig cell tumors is 80%, and long-term follow-up is therefore highly advised in this patient. PMID- 26893702 TI - Overexpression of S100A14 in human serous ovarian carcinoma. AB - S100 calcium binding protein A14 (S100A14) is a member of the S100 protein family that plays an important role in the progression of several types of cancer. In the present study, the expression and clinical effect of S100A14 was evaluated in serous ovarian carcinoma (SOC). SOC tissue specimens and a panel of normal ovarian and fallopian tubal tissue specimens were obtained between November 2008 and August 2012 from the Affiliated Hospital of Qingdao University. Immunohistochemistry (IHC) was used to detect the expression of S100A14 in the SOC and normal control tissues. In addition, ELISA was performed to assess S100A14 expression in a subset of serum samples. The association between the expression of S100A14 in SOC and the corresponding clinical and pathological data was analyzed. The IHC results revealed that S100A14 was mainly located in the cytoplasm of the majority of SOC cells, and the expression levels of S100A14 in the tumor tissues were significantly increased compared with the levels identified in normal ovarian specimens (P<0.001). Consistently, the serum levels of S100A14 in patients with SOC were also increased compared with the levels in healthy individuals (P<0.001). S100A14 expression was similar in the epithelium of SOC lesions and the fallopian tube, which supported the dualistic model for ovarian serous carcinogenesis. Additional analysis of the expression of S100A14 and corresponding clinical and pathological data revealed the correlation between the elevated expression of S100A14 and resistance to platinum-based chemotherapy. However, the protein level of S100A14 was not associated with the pathological stage, differentiation or metastasis of SOC. Overall, the present results demonstrate that S100A14 is likely to be involved in the resistance of SOC to platinum-based chemotherapy. PMID- 26893703 TI - A peripheral primitive neuroectodermal tumor in the larynx: A case report and literature review. AB - Primitive neuroectodermal tumors (PNETs) are malignant tumors comprised of small round cells of neuroectodermal origin. Current evidence indicates that peripheral PNETs (pPNETs), which arise in the non-central nervous system, possess histological similarity to Ewing's sarcoma. Though the occurrence of pPNETs in the head and neck region is rare, these are aggressive malignant tumors, and long term survival rates following diagnosis remain poor. The current report presents a case of pPNET and evaluates its significance with regard to previous studies. In the present case, a tumor was located in the larynx of the patient, and was diagnosed as pPNET. Immunohistochemical analysis indicated that tumor cells were positive for cluster of differentiation 99. The patient was treated with surgery, multiagent chemotherapy and radiotherapy. Five years subsequent to treatment, the patient had survived and demonstrated no evidence of disease recurrence. In existing literature concerning pPNET located outside the head and neck region, it is recommended that patients are treated with a combination of resection with a wide surgical margin, multiagent chemotherapy and radiotherapy. The present case report concluded that the combination of surgery, systematic chemotherapy and radiotherapy, offers an improved outcome for pPNET localized to the head and neck region, compared with any of these therapies alone. PMID- 26893704 TI - Ovarian involvement of a desmoplastic small round cell tumor of unknown primary origin with lymph node and lung metastases: A case report. AB - Desmoplastic small round cell tumors (DSRCTs) were initially characterized as exhibiting divergent differentiation and were extremely aggressive, belonging to the family of 'small round blue cell tumors'. Due to a male predominance, to date, only 15 cases in women have been reported in the English literature. The present study describes a case of DSRCT in a young woman who initially presented with ovarian masses accompanied with lymph node and lung metastases. A correct diagnosis was reached by combining the hematoxylin and eosin, and immunohistochemical staining results. Following surgery, the patient underwent the chemotherapy and, 3 months later, is in a good condition. The study also provides an overview of this uncommon disease. PMID- 26893705 TI - A giant neurothekeoma of the left shoulder blade: A case report. AB - Neurothekeoma is a rare myxoma of the peripheral nerve sheath. The current report presents a case of a giant neurothekeoma with a partially-formed capsule, scapula erosion and unclear biological behavior, which originated in the intermuscular space between the left trapezius muscle and scapula. The patient was initially misdiagnosed with a fibromatosis using computed tomography and magnetic resonance image scanning. Diagnosis of the neoplasm was confirmed by pathological and immunohistochemical examination, revealing a neurothekeoma with unclear biological behavior. The patient underwent a wide and complete local resection. Using a comprehensive postoperative follow-up strategy, it was determined that the patient recovered well. The tumor was ~17*16*10 cm in size and was in contact with the scapula. The purpose of the present study was to describe a rare giant neurothekeoma and review the diagnostic techniques utilized to reach a definitive diagnosis. Histopathological and immunohistochemical analyses were recommended for the diagnosis of neurothekeoma. There have been no previous reports regarding neurothekeomas exhibiting malignant transformation. Early and complete surgical resection is considered to be an effective method of treating this type of neurothekeoma. PMID- 26893706 TI - Situs inversus totalis with a mature teratoma of the posterior mediastinum: A case report. AB - Situs inversus totalis is an unusual disease with a low incidence. The co existence of situs inversus totalis with a teratoma is extremely rare. To the best of our knowledge, there is no data on the association between situs inversus totalis and teratoma in the literature. The present study therefore describes the first such case in a 23-year-old female. The patient presented with intermittent chest tightness, which had lasted for ~3 years. Following radiological examination, the patient was diagnosed with situs inversus totalis and a mature teratoma in the posterior mediastinum. Surgical resection was performed to remove the teratoma and the patient subsequently made a full recovery. Follow-up X-ray and computed tomography examinations were performed 6 months after surgery, which revealed no disease recurrence. PMID- 26893707 TI - Continuous prostate-specific antigen rise despite salvage radiotherapy following radical prostatectomy: Pattern of clinical relapse and predictive factors. AB - Salvage radiotherapy for post-prostatectomy biochemical recurrence does not always control the disease. It would be useful to identify patients who would not benefit from radiotherapy to the prostate bed prior to making treatment recommendations. One such group of patients is those who experience continuously rising prostate-specific antigen (PSA) despite radiotherapy. The purpose of this study was to identify risk factors for continuous PSA increase and the pattern of radiological relapse during follow-up. We performed a retrospective comparison of two patient groups with PSA decline or continuous increase following salvage radiotherapy to the prostate bed. All patients received 3-D conformal radiotherapy (35 fractions of 2 Gy). Patients with continuous PSA increase were more likely to have had complete surgical resection (negative margins) and a shorter interval to radiotherapy (<24 months). However, the only statistically significant risk factor was Gleason score. Sixty-four percent of patients with a Gleason score of 9 developed continuously increasing PSA, indicating that residual subclinical cancer was not located in the prostate bed. The median time to radiological recurrence was 43 months. Isolated pelvic nodal recurrence was uncommon. Almost all patients with radiological recurrence had high-risk disease, in particular stage pT3. In conclusion, the majority of patients with biologically aggressive tumors with Gleason score 9 were not adequately treated with prostate bed radiotherapy alone. The predominant pattern of radiological recurrence was outside of the pelvis. Therefore, the problem of distant micrometastases has to be addressed. PMID- 26893708 TI - Acute lymphocytic leukemia mimicking spondyloarthritis in an adolescent: A case report and review of the literature. AB - The present study describes the case of an 18-year-old adolescent male exhibiting acute lymphocytic leukemia (ALL), complicated by the onset of the symptom of sacroiliitis mimicking spondyloarthritis. Atypical features including an enlarged spleen, poor effects of non-steroidal anti-inflammatory drug therapy, low levels of hemoglobin, a low platelet count, a low neutrophil count and increased levels of monocytes, indicated the possibility of hematological malignancy. Bone marrow examination confirmed the diagnosis of ALL. The patient received chemotherapy and the symptoms were dramatically relieved. To the best of our knowledge, the current study reports the second published case of a patient with ALL presenting with sacroiliitis. Sacroiliitis as an onset manifestation of ALL may result in misdiagnosis, therefore, a differential diagnosis is essential when atypical features are present. PMID- 26893709 TI - Aneurysmal bone cyst on the left zygomatic arch concomitant with bilateral inferior turbinate gasification in an adult female: A case report. AB - The simultaneous occurrence of an aneurysmal bone cyst (ABC) on a zygomatic arch with bilateral inferior turbinate gasification is extremely rare, and no previous studies are available. Here we report the case of a 34-year-old Chinese Han female who presented with hyperplasia of the left maxillary bone for one and a half years. The patient was observed to have an ABC on the left zygomatic arch concomitant with bilateral inferior turbinate gasification, as indicated by X-ray computed tomography, contrast-enhanced computed tomography and three-dimensional maxillofacial reconstruction. The patient underwent surgical resection of the cyst, and no postoperative symptoms were observed during the 4 years of follow up. The etiology of this case is considered to be associated with a gene abnormality. PMID- 26893710 TI - Targeting of NHERF1 through RNA interference inhibits the proliferation and migration of metastatic prostate cancer cells. AB - The present study aimed to investigate the effects of Na+/H+ exchanger regulatory factor 1 (NHERF1) gene knockdown, using short-hairpin RNA (shRNA), on the malignant behaviors of prostate cancer cells. A pSuper.puro NHERF1 shRNA vector was transfected into PC-3M prostate cancer cells using Lipofectamine 2000. Stable cell lines were obtained and NHERF1 knockdown was verified through western blot analysis. MTT assays were then used to measure PC-3M cell proliferation; in addition, cell migration was assessed using a wound healing assay. Flow cytometry was employed in order to determine the effects of NHERF1 knockdown on apoptosis. Expression levels of apoptotic pathway proteins B cell lymphoma-2 (Bcl-2) and Bcl 2-associated X protein were then determined by western blot analysis. The results demonstrated that shRNA knockdown of NHERF1 significantly suppressed the proliferation of PC-3M cells by >50%. In addition, knockdown of NHERF1 significantly inhibited the migration of PC-3M cells. PC-3M cells harboring NHERF1 shRNA exhibited significantly increased apoptosis, with an ~4-fold increase compared with that of the parental PC-3M cells and cells transfected with an empty vector. Furthermore, the results revealed that knockdown of NHERF1 reduced the protein expression of Bcl-2, although the expression of Bax was unaltered. In conclusion, NHERF1 knockdown using shRNA inhibited the proliferation and migration of PC-3M cells and promoted apoptosis, highlighting the role of NHERF1 in prostate cancer progression. PMID- 26893711 TI - Downregulation of miR-362-5p inhibits proliferation, migration and invasion of human breast cancer MCF7 cells. AB - An increasing number of studies have indicated that the deregulation of microRNAs (miRNAs) contributes to tumorigenesis and metastasis. In the present study, significant upregulation of miR-362-5p was identified in the breast cancer MDA-MB 231 and MCF7 cell lines compared with the control CCD-1095Sk cell line. The inhibition of miR-362-5p was demonstrated to significantly inhibit the cell proliferation, migration and invasion of human breast cancer MCF7 cells. In addition, the knockdown of miR-362-5p induced G1 arrest and promoted apoptosis in the breast cancer cells. Mechanistic investigations confirmed that the tumor suppressor gene CYLD is a direct target of miR-362-5p. The ectopic expression of miR-362-5p represses CYLD expression, whereas miR-362-5p inhibitor treatment induces CYLD protein expression and decreases NF-kappaB expression in the downstream signaling pathway. Thus, these findings may provide novel insights into the molecular mechanisms through which miR-362-5p regulates breast cancer cell proliferation, migration and invasion. This study also suggests that miR-362 5p may act as a novel potential therapeutic target for the treatment of breast cancer. PMID- 26893712 TI - Effect of miR-155 knockdown on the reversal of doxorubicin resistance in human lung cancer A549/dox cells. AB - Doxorubicin has been widely used in the treatment of cancer. However, acquired doxorubicin resistance severely hinders the application of the drug. In the present study, doxorubicin resistance was investigated in lung carcinoma. microRNA-155 (miR-155) was found to be upregulated in the doxorubicin-resistant A549/dox cell line. Suppression of miR-155 in this cell line considerably reversed doxorubicin resistance, and doxorubicin-induced apoptosis and cell cycle arrest were recovered. Furthermore, reverse transcription-polymerase chain reaction and western blot analysis revealed that miR-155 suppression downregulated the expression of multidrug resistance protein 1, multidrug resistance-associated protein 1, breast cancer resistance protein, glutathione S transferase-pi, Survivin and B-cell lymphoma 2, and upregulated the expression of caspase-3 and caspase-8. In addition, it was found that miR-155 suppression inhibited the activation of AKT and extracellular signal-regulated kinase. The transcriptional activity of nuclear factor-kappaB and activator protein-1 was also downregulated. In summary, the present results indicate that miR-155 may participate in doxorubicin resistance in lung carcinoma. The current study provides a novel target for lung carcinoma treatment. PMID- 26893713 TI - Expression and clinical significance of Sirt1 in colorectal cancer. AB - The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis. PMID- 26893714 TI - Glaucocalyxin A inhibits the growth of liver cancer Focus and SMMC-7721 cells. AB - Liver cancer is one of the most common types of cancer, and hepatoma demonstrates a poor long-term prognosis. The present study reports that glaucocalyxin A (GLA), a natural product isolated from Rabdosia umbrosa, inhibits the growth of the liver cancer Focus and SMMC-7721 cell lines in a dose- and time-dependent manner. The present study revealed that GLA arrested the liver cancer cells at the G2/M stage of the cell cycle and led to decreased expression of caspase 3 and the cleavage of poly(adenosine diphosphate-ribose) polymerase. Overall, the present study demonstrated that GLA inhibits the growth of liver cancer cells by G2/M stage cell-cycle arrest and cell apoptosis. PMID- 26893715 TI - Bilateral spontaneous pneumothorax in an osteosarcoma patient with pulmonary metastases: A case report. AB - Spontaneous pneumothorax is a rare complication of chemotherapy in the treatment of lung neoplasms. It is relatively common in osteosarcoma lung metastases patients following chemotherapy, but the cause is still unknown. Here, we report a case of bilateral spontaneous pneumothorax occurring in a 40-year-old female in whom lung metastases from osteosarcoma were treated with combination chemotherapy. The patient had osteosarcoma on the right side of the mandible, and developed bilateral spontaneous pneumothorax. Through contrasting chest computed tomography, pneumothorax was identified at the site of the pulmonary metastases and occurred following the formation of bullae. The pneumothorax and bullae were produced after the patient received chemotherapy. In October 2014, the patient succumbed to the disease due to hemorrhage of the primary osteosarcoma lesions. PMID- 26893717 TI - Downregulation of BC200 in ovarian cancer contributes to cancer cell proliferation and chemoresistance to carboplatin. AB - Previous studies have demonstrated that long non-coding RNAs (lncRNAs) serve an important role in carcinogenesis. BC200 is a lncRNA that is reportedly associated with ovarian cancer. The aim of the present study was to investigate this potential association between BC200 and ovarian cancer, and to subsequently analyze the biological function of BC200 in the disease. BC200 expression was compared in ovarian cancer tissue and normal ovarian tissue samples through the use of quantitative polymerase chain reaction. To allow the biological function of BC200 in ovarian cancer to be analyzed, small interfering RNA was used to knock down the expression of BC200 in SKOV3 and A2780 ovarian cancer cells. The proliferative, invasive and migratory abilities of the cells were identified by means of cell counting kits and Transwell assays. Carboplatin was also used to treat the ovarian cancer cells, and a luminescent cell viability assay was subsequently used to detect the sensitivity of the cells to the carboplatin. The results demonstrated that BC200 expression was reduced in ovarian cancer compared with normal ovarian tissue samples. In the SKOV3 and A2780 cells, BC200 exerted no effect on invasive or migratory ability, however, the inhibition of BC200 was demonstrated to promote cell proliferation. Additionally, it was observed that carboplatin induced BC200 expression in the cell lines, and that the inhibition of BC200 decreased the sensitivity of the cells to the drug. BC200 is therefore likely to have a tumor suppressive function in ovarian cancer by affecting cell proliferation. Furthermore, BC200 appears to serve a role in the mediation of carboplatin-induced ovarian cancer cell death. PMID- 26893716 TI - Polymorphic variants in the vitamin D pathway genes and the risk of ovarian cancer among non-carriers of BRCA1/BRCA2 mutations. AB - Previous studies have produced inconsistent results regarding the contribution of single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene to ovarian cancer (OC) in various ethnicities. Additionally, little has been established with regard to the role of SNPs located in the retinoid X receptor alpha (RXRA), vitamin D-binding protein [also know as group-specific component (GC)] and VDR genes in non-carriers of the breast cancer 1/2 early onset (BRCA1/BRCA2) gene mutations. All participating individuals in the present study were evaluated for BRCA1 mutations (5382incC, C61G and 4153delA) with HybProbe assays, and for BRCA2 mutation (5946delT) using high-resolution melting (HRM) analysis. The associations of 8 SNPs located in RXRA, GC and VDR were investigated in OC patients without the BRCA1/BRCA2 mutations (n=245) and healthy controls (n=465). Genotyping of RXRA rs10881578 and rs10776909, and GC rs1155563 and rs2298849 SNPs was conducted by HRM analysis, while RXRA rs749759, GC rs7041, VDR BsmI rs1544410 and FokI rs2228570 genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. In addition, the gene-gene interactions among all tested SNPs were studied using the epistasis option in PLINK software. The lowest P-values of the trend test were identified for VDR rs1544410 and GC rs2298849 as Ptrend=0.012 and Ptrend=0.029, respectively. It was also found that, in the dominant inheritance model, VDR BsmI contributed to an increased risk of OC [odds ratio (OR), 1.570; 95% confidence interval (CI), 1.136-2.171; P=0.006; Pcorr=0.048]. The gene-gene interaction analysis indicated a significant interaction between RXRA rs749759 and VDR FokI rs2228570 (OR for interaction, 1.687; chi2=8.278; asymptotic P-value=0.004; Pcorr=0.032). In conclusion, this study demonstrated that certain VDR and RXRA SNPs may be risk factors for OC in non-carriers of BRCA1/BRCA2 mutations in the Polish population. PMID- 26893718 TI - Picfeltarraenin IA inhibits lipopolysaccharide-induced inflammatory cytokine production by the nuclear factor-kappaB pathway in human pulmonary epithelial A549 cells. AB - The present study aimed to investigate the effect of picfeltarraenin IA (IA) on respiratory inflammation by analyzing its effect on interleukin (IL)-8 and prostaglandin E2 (PGE2) production. The expression of cyclooxygenase 2 (COX2) in human pulmonary adenocarcinoma epithelial A549 cells in culture was also examined. Human pulmonary epithelial A549 cells and the human monocytic leukemia THP-1 cell line were used in the current study. Cell viability was measured using a methylthiazol tetrazolium assay. The production of IL-8 and PGE2 was investigated using an enzyme-linked immunosorbent assay. The expression of COX2 and nuclear factor-kappaB (NF-kappaB)-p65 was examined using western blot analysis. Treatment with lipopolysaccharide (LPS; 10 ug/ml) resulted in the increased production of IL-8 and PGE2, and the increased expression of COX2 in the A549 cells. Furthermore, IA (0.1-10 umol/l) significantly inhibited PGE2 production and COX2 expression in cells with LPS-induced IL-8, in a concentration dependent manner. The results suggested that IA downregulates LPS-induced COX2 expression, and inhibits IL-8 and PGE2 production in pulmonary epithelial cells. Additionally, IA was observed to suppress the expression of COX2 in THP-1 cells, and also to regulate the expression of COX2 via the NF-kappaB pathway in the A549 cells, but not in the THP-1 cells. These results indicate that IA regulates LPS induced cytokine release in A549 cells via the NF-kappaB pathway. PMID- 26893719 TI - Increased oncogenic microRNA-18a expression in the peripheral blood of patients with prostate cancer: A potential novel non-invasive biomarker. AB - MicroRNAs have been demonstrated to be stably detectable in peripheral blood, thus representing important sources of non-invasive biomarkers of various diseases, including cancer. Recently, microRNA-18a (miR-18a) has been revealed to be highly expressed in prostate cancer (PC) tissues, acting as an oncogenic miRNA. The present study evaluated miR-18a expression in the peripheral blood of patients with PC, patients with benign prostatic hyperplasia (BPH), and healthy individuals, to assess the feasibility of using peripheral blood miR-18a as a potential non-invasive biomarker for PC. Total RNA was extracted from peripheral whole blood samples from 24 PC patients, 24 BPH patients and 23 healthy control individuals. The expression of miR-18a was assessed by reverse transcription quantitative polymerase chain reaction. The results revealed that miR-18a expression was significantly higher in PC patients than in BPH patients and healthy controls [fold change (mean +/- standard deviation), 5.5+/-1.4 for PC, 1.5+/-0.5 for BPH and 1.2+/-0.6 for controls; P<0.005]. Higher miR-18a expression was strongly associated with PC [odds ratio (OR), 4.602; 95% confidence interval (CI), 2.194-9.654; P=0.001], but was not significantly associated with BPH (OR, 1.2; 95% CI, 0.7-2.02; P=0.332). Despite the small number of patients, which limits the statistical power of the study, higher miR-18a expression was observed to be significantly correlated with certain clinicopathological parameters, including Gleason score >7 and pathological tumor stage 3/4 (P<0.005). A receiver operating characteristic (ROC) analysis revealed that miR-18a discriminated PC patients from BPH patients and healthy controls [area under the curve (AUC), 0.805; 95% CI, 0.704-0.906). Furthermore, use of the ROC curve to discriminate PC from BPH patients yielded an AUC of 0.878 (95% CI, 0.783-0.972). In summary, the present results indicate that miR-18a expression is significantly increased in peripheral blood of patients with PC compared with that of BPH patients and healthy individuals, and that higher miR-18a expression is associated with progression of PC. Peripheral blood oncogenic miR-18a may serve as a potential novel non-invasive biomarker for PC that also facilitates discrimination between PC and BPH. PMID- 26893720 TI - MicroRNA-126 inhibits the migration and invasion of endometrial cancer cells by targeting insulin receptor substrate 1. AB - MicroRNAs (miRs) have been demonstrated to serve important roles in the development and progression of human cancer, primarily through the direct targeting of oncogenes or tumor suppressors. It has been previously suggested that miR-126 may be associated with endometrial cancer (EC). However, the exact role of miR-126 in the migration and invasion of EC cells has not yet been studied. The present study demonstrated that the expression of miR-126 was significantly decreased in EC tissues when compared with matched normal adjacent tissues. The current study reverse transcription-quantitative polymerase chain reaction was performed in order to examine the expression level of miR-126. Wound healing and transwell assays were used to examine cell migration and invasion. A luciferase reporter assay was used to determine the targeting relationship and western blotting assay was performed to detect the protein expression. Furthermore, the overexpression of miR-126 significantly inhibited EC SKOV3 cell migration and invasion. Molecular mechanism investigation established that insulin receptor substrate 1 (IRS1) functioned as a direct miR-126 target, and its expression was negatively regulated by miR-126 at a post-transcriptional level in the SKOV3 cells. Additionally, the overexpression of IRS1 reversed the inhibitory effect of miR-126 overexpression on SKOV3 cell migration and invasion. In conclusion, the current study demonstrated that miR-126 inhibited EC cell migration and invasion, at least partially through the direct targeting of IRS1, suggesting that miR-126 may aid the treatment of EC metastasis. PMID- 26893721 TI - Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation. AB - The aim of the current study was to diagnose the concomitant presence of adenomyosis (AM) in endometrioid endometrial cancer (EEC) in order to evaluate its value as an oncological prognostic marker. A retrospective analysis of 289 patients diagnosed with EEC who underwent total hysterectomy, bilateral salpingo oophorectomy and pelvic-lymphadenectomy was conducted. The total cohort included 37 patients in Group A (those with concomitant AM and EEC) and 252 patients in Group B (those affected only by EEC). The following factors were evaluated: Presence or absence of AM, tumor grade, depth of myometrial invasion, tumor size, lymphovascular space involvement, lymph node status, peritoneal cytology, concomitant detection of endometrial atypical-hyperplasia or polypoid endometrial features and tumor stage according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Uterine examination of different sections of uterine cervix, corpus, myomas and cervical or endometrial polyps was performed. The diagnosis of AM was confirmed when the distance between the lower border of the endometrium and the foci of the endometrial glands and stroma was >2.5 mm. Parametric and nonparametric statistical tests were performed when possible; continuous variables were analyzed using a Student's t-test, and categorical variables were analyzed by the chi2 test or Fisher's exact test. The association between FIGO stage and group was determined to be significant: 83.8% of Group A patients were categorized as FIGO stage I, vs. 68.7% of Group B patients. In addition, Group A was associated with lower grades in FIGO stage, myometrial invasion, lymphovascular space involvement, lymph node involvement and tumor size. The findings suggest that the intraoperative evaluation of the presence of AM in patients with EEC may aid surgeons in estimating oncological risk and in selecting the most appropriate surgical treatment. PMID- 26893722 TI - Papillary oncocytic cystadenoma of a palatal minor salivary gland: A case report. AB - Papillary cystadenomas of the salivary gland are uncommon, benign, encapsulated or well-circumscribed, multicystic tumors with intracystic papillations. In a large review, papillary cystadenoma constituted 2% of all minor salivary gland tumors. The present study reports an extremely rare case of a papillary cystadenoma arising from the palate that demonstrated oncocytic features. A 60 year-old man was referred by his dentist to the Second Department of Oral and Maxillofacial Surgery at Osaka Dental University Hospital for the diagnostic evaluation of a mass of the left palate. An incisional biopsy was performed and the microscopic findings were interpreted as consistent with a papillary oncocytic cystadenoma. Therefore, the lesion was excised under general anesthesia. The post-operative course was uneventful and no recurrence had developed 5 years subsequent to surgery. PMID- 26893723 TI - Association between the expression levels of TAZ, AXL and CTGF and clinicopathological parameters in patients with colon cancer. AB - Colon cancer accounts for a large proportion of all the cancer-associated morbidities worldwide. Genetic analysis and stratification of patients based on survival may identify genetic signatures potentially useful for prognostic or treatment planning purposes. Previous studies have reported that the messenger (m)RNA expression levels of tafazzin (TAZ), AXL receptor tyrosine kinase (AXL) and connective tissue growth factor (CTGF) were able to predict the survival of patients with colon cancer in two independent colon cancer datasets. However, limited clinicopathological data were available from these two datasets. By contrast, a large colon cancer dataset comprising 566 patients has been recently published in the Gene Expression Omnibus database, which contains data regarding tumor stage and location, and genetic status of mismatch repair (MMR), Kirsten rat sarcoma viral oncogene homolog (KRAS), B-Raf proto-oncogene serine/threonine kinase (BRAF) and tumor protein p53 (TP53). In the present study, the mRNA expression levels of TAZ, AXL and CTGF were evaluated, and the TAZ-AXL-CTGF signature was correlated with the available pathological parameters and survival data. Overexpression of TAZ, AXL and CTGF was observed to be associated with severe pathological stage, deficiency in MMR, colon cancer subtype C4 and mutations in the BRAF gene. In addition, overexpression of TAZ-AXL-CTGF was associated with short overall survival in patients with mutations in the TP53 gene, colon cancer subtype C6, proficient MMR and wild-type status of the KRAS and BRAF genes. Furthermore, the prognostic value of TAZ-AXL-CTGF overexpression was observed to be independent of all the clinicopathological parameters and mutational statuses analyzed. The results of the present study confirm the previously reported findings, and suggest that the TAZ-AXL-CTGF mRNA signature is a potential prognostic indicator in colon cancer. PMID- 26893724 TI - Incidence and risk factor analysis for sarcopenia in patients with cancer. AB - The objective of the present study was to investigate the incidence of and possible risk factors associated with sarcopenia among cancer patients. Patients with cancer were examined through the use of lumbar magnetic resonance imaging, and clinical data was collected between September and December, 2012, at Jilin Province Tumor Hospital (Changchun, China). The data was subsequently compared between patients with and without sarcopenia. Of the 113 treated cancer patients, 96 patients [39 males (L3 index, <52.4 cm2/m2) and 57 females (L3 index, <38.5 cm2/m2)] suffered from sarcopenia. Overall, the development of sarcopenia was not significantly associated with patient age or treatment, including surgery, chemotherapy or radiotherapy (P>0.05). The frequency of treatment-associated complications did not differ significantly between patients with or without sarcopenia. However, males were more inclined to develop sarcopenia than females (P=0.02). Patients with sarcopenia had significantly less lymphocytes than patients without sarcopenia (P=0.03). This was confirmed through multiple logistic regression analyses (P=0.046), which also identified that patients with cancer with an Eastern Cooperative Oncology Group score >2 had a significantly increased risk of developing sarcopenia. Finally, the serum albumin level in sarcopenia patients was 36.18+/-4.65 g/l, which was not significantly less than that of patients without sarcopenia (39.67+/-3.69 g/l; P=0.11). The incidence of sarcopenia among patients with cancer is high, particularly for males. Further research with larger sample sizes would be beneficial, with the aim of verifying the results obtained in the present study. During the treatment of patients with sarcopenia, precaution should continue to be taken to prevent associated complications, including infection, diarrhea and myelosuppression. PMID- 26893725 TI - Oncogenic microRNA-142-3p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. AB - MicroRNAs (miRNAs/miRs) serve an important role in the regulation of carcinogenic pathways. RCC is the most prevalent kidney cancer that occurs in adults. miRNAs have gained increasing attention due to their association with RCC tumorigenesis, serving as biomarkers for early detection and progression monitoring, and as potential targets for molecular therapy. Upregulation of miRNA-142-3p has been previously identified in RCC tissues by microarray profile, however, its expression and function in RCC have not yet been validated. In the present study, quantitative polymerase chain reaction was performed to quantify the relative expression of miR-142-3p in 53 paired RCC and adjacent normal tissues. Furthermore, wound healing, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays were performed to analyze the impacts of miR 142-3p on cellular migration, proliferation and apoptosis. The results demonstrated that miR-142-3p was significantly upregulated in RCC tissues compared with adjacent normal tissues. Downregulation of miR-142-3p, induced by chemically synthesized miR-142-3p inhibitor, significantly suppressed cell migration and proliferation, and promoted cell apoptosis in 786-O and ACHN cells, supporting the theory that miR-142-3p may function as an oncogene in RCC. The potential clinical significance of miR-142-3p, as a biomarker and therapeutic target, provides rationale for further investigation into the miR-142-3p-mediated molecular pathway and how it is associated with RCC development. PMID- 26893726 TI - Combined RNAi targeting human Stat3 and ADAM9 as gene therapy for non-small cell lung cancer. AB - Previous studies have demonstrated that human signal transducer and activator of transcription 3 (Stat3) and disintegrin and metalloproteinase 9 (ADAM9) are promising targets for RNA interference (RNAi)-based gene therapy for human non small cell lung cancer (NSCLC). Thus, in the present study, the recombinant lentiviral (Lv) small hairpin (sh)RNA expression plasmids Lv/sh-Stat3 and Lv/sh ADAM9, which targeted Stat3 and ADAM9, respectively, were constructed and subsequently infected into the A549 human NSCLC cell line. Cell proliferation, migration, invasion and apoptosis were determined in vitro in A549 cells following treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone or in combination. In addition, the combined effect of Lv/sh-Stat3 and Lv/sh-ADAM9 gene therapy was evaluated in vivo using A549 xenograft models in nude mice. The in vitro experiments demonstrated that A549 cells treated with a combination of Lv/sh Stat3 and Lv/sh-ADAM9 exhibited a significant additive effect in their cell proliferation, migration, invasion and apoptosis abilities, compared with A549 cells treated with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. The in vivo experiments conducted in A549 xenograft tumor mouse models revealed that the combined treatment with Lv/sh-Stat3 and Lv/sh-ADAM9 exerted an additive effect on tumor growth inhibition, compared with the treatment with Lv/sh-Stat3 or Lv/sh-ADAM9 alone. These results suggested that combined RNAi gene therapy targeting human Stat3 and ADAM9 may be a novel and promising strategy for the treatment of NSCLC. PMID- 26893727 TI - Novel cyclic pentapeptide H-15 induces differentiation and inhibits proliferation in murine melanoma B16 cells. AB - Sansalvamide A is a cyclic depsipeptide that is isolated from a marine fungus of the Fusarium genus. Sansalvamide A exhibits significant antitumor ability. The molecular formula and molecular weight of the novel sansalvamide A derivative H 15 are C29H44BrN5O6 and 637.2475, respectively. In the present study, H-15 was found to inhibit the proliferation and induce the differentiation of murine melanoma B16 cells. A sulforhodamine B colorimetric assay was used to measure the inhibitory effects of 0.1, 1, 10, 50 and 100 uM H-15 on the B16 cells, and the results revealed that the inhibitory effects of H-15 exerted on the B16 cells occurred in a concentration-dependent manner. In addition, the growth curve model of the B16 cells treated with 50 uM H-15 revealed that the effect of H-15 was also time-dependent. The differentiation morphology of the B16 cells was observed subsequent to treating the cells with H-15. An optical microscope was used to observe the differentiation morphology of the cells. In addition, melanin secretion increased in the B16 cells treated with 50 uM H-15. The expression levels of tyrosinase (TYR) were assayed by western blot analysis, and it was found that the cells treated with 50 uM H-15 for 48 h exhibited increased expression of TYR. The results of the present study indicated that H-15 may induce the differentiation of B16 cells. PMID- 26893729 TI - CORRIGENDUM. AB - [This corrects the article DOI: 10.3892/ol.2015.3625.]. PMID- 26893728 TI - In vitro analysis of the anticancer properties of scorpion venom in colorectal and breast cancer cell lines. AB - Scorpion venom contains various types of proteins and peptides that are able to act as inhibitors of neurotransmitter molecules. This is achieved primarily via the inhibition of ion channels. In addition, scorpion venom has been demonstrated to exhibit anticancer properties in prostate and breast cancer, as well as leukemia. The anticancer properties of scorpion venom are due to its inhibitory effect on matrix metalloproteinase (MMP) activity, which leads to reduced motility and invasion in tumor cells. The inhibitory effects of venom on MMPs additionally lead to a reduction in the metastatic potential of malignant tumors. In the present study, the effect of venom obtained from a local serpentarium facility was examined in colorectal and breast cancer cell lines. Cell motility and clonogenic survival assays revealed a significant decrease (60-90%) in cell motility and colony formation, two significant hallmarks of cancer survival, following treatment with various concentrations of venom. These results were in agreement with previous studies demonstrating the anticancer activity of scorpion venom. In conclusion, the venom utilized at the Research Center of Prince Sultan Military Medical City Hospital (Riyadh, Saudi Arabia) possesses significant anticancer potential against colorectal and breast cancer cell lines. PMID- 26893730 TI - MicroRNAs in diffuse large B-cell lymphoma. AB - The aberrant expression of microRNAs (miRs) has a significant impact on the biological characteristics of lymphocytes, and is important in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). It has been demonstrated, using miR profiling and detecting distinct miR signatures, that certain miRs may accurately distinguish different subtypes and prognostic classifications of DLBCL, as well as distinguish DLBCL from other more indolent lymphomas, including follicular lymphoma. miRs are excellent biomarkers for cancer diagnosis and prognosis. In DLBCL, specific miR expression profiles in the tissues of patients are associated with prognosis and clinical outcome. Over the past decade, there has been substantial investigation concerning the pathogenetic, diagnostic and prognostic roles of miRs in DLBCL. The aim of the present review is to describe the aberrant expression of miRs in DLBCL, and the functions, potential clinical use and possible therapeutic targets of miRs in this disease. PMID- 26893733 TI - Circulating tumor cell count as a biomarker of a specific gastric cancer subgroup characterized by bone metastasis and/or disseminated intravascular coagulation - an early indicator of chemotherapeutic response. AB - The incidence of gastric cancer coupled with multiple bone metastases, and/or disseminated intravascular coagulation (DIC), is characterized by the clinical presentation of rapid progression and a poor prognosis, and differs from typical gastric cancers. Circulating tumor cells (CTCs) are negligible in typical advanced gastric cancers, however, a considerable number of CTCs in the bloodstream may be detected in the subgroup demonstrating multiple bone metastases and/or DIC. The present study analyzed two cases, with the first case regarding a 51-year-old male who exhibited a CTC count of 275 cells/7.5 ml following an initial, ineffective, chemotherapy cycle. The patient underwent a second chemotherapy course that was effective, and the cell count was observed to reduced to 2 cells/7.5 ml. A decreased CTC count was first confirmed on day 16 following treatment. During the chemoresistant phase, the CTC count was observed to increase again. The second case presented by the current study describes a 59 year-old female who exhibited a CTC count of 235 cells/7.5 ml prior to chemotherapy. This subsequently decreased to 7 cells/7.5 ml following an effective course of chemotherapy. Notably, the CTC count increased alongside disease progression in this case. Within the rare subgroup of gastric cancer patients with multiple bone metastases and/or DIC, CTC count may serve as an early biomarker allowing the evaluation of therapeutic efficacy. However, due to the aggressive nature of this type of cancer, imaging analysis is not recommended as it may typically take several months to complete. PMID- 26893731 TI - Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges. AB - Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed. PMID- 26893732 TI - Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning. AB - Metformin is a first-line drug used for the treatment of type 2 diabetes. Recently, metformin has been reported to reduce the carcinogenic risk and inhibit tumor cell growth in glioma and breast cancer. The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth. Metformin is anticipated to exert antitumor effects in gynecological cancer, and its efficacy for the treatment of endometrial, breast and ovarian cancer has been suggested in preclinical studies and clinical trials. Although the effect of metformin on cervical cancer remains to be examined in clinical trials, its antitumor effects have been reported in preclinical studies. Thus, the use of metformin for the treatment of gynecological cancer may become a successful example of drug repositioning, following establishment of the drug's antitumor effects, risk evaluation, screening and validation of efficacy. PMID- 26893734 TI - Screening and identification of post-traumatic stress-related serum factors in children with Wilms' tumors. AB - Wilms' tumors are one of the most common malignant, solid intra-abdominal tumors observed in children. Although potential tumor markers have been found, inflammatory cytokines interfere with the process of specific protein identification. The present study was undertaken to identify post-traumatic stress-related factors of Wilms' tumors and to verify the accuracy of early-stage tumor-specific serum protein markers. Serum samples were screened for differentially-expressed proteins using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Potential markers were isolated and purified using solid-phase extraction (SPE) and SDS PAGE. Following enzymatic digestion of the protein samples, the peptide fragments were detected with high performance liquid chromatography-mass spectrometry. The obtained peptide mass fingerprint was searched in the Swiss-Prot protein sequence database via the Mascot search engine. Differentially-expressed proteins were verified using western blot analysis. Differentially-expressed proteins with a mass/charge of 5,816 were screened out using SELDI-TOF-MS, and significant differences between the tumor and control groups, and the trauma and control groups were observed. Target proteins were isolated and purified using SPE and SDS-PAGE. Thioredoxin 1 (Trx1) was found to be differentially expressed. In the serum of children with Wilms' tumors, there was an increase in the level of the post-traumatic stress-related inflammatory factor, Trx1, as compared with the normal control group. Thus, the results of this study indicate that Trx1 presents a potential post-traumatic stress-related factor of Wilms' tumors. PMID- 26893735 TI - Hearing loss due to metastasis of gastric cancer to temporal bone: A case report. AB - Metastatic temporal bone tumors are rare, and tend to be asymptomatic. The clinical symptoms consist of aural discharge, bleeding, hearing loss and facial nerve paresis. The most common origin of the metastasis is breast cancer, and other sites of the primary tumor include the thyroid gland, brain, lungs, prostate and blood. Clinical reports of hearing loss due to gastric cancer metastatic to temporal bone are rare. In the present study, a case of gastric cancer metastasis to temporal bone without other organ involvement is described. The patient presented with the symptom of hearing loss, and the metastatic tumor was diagnosed by radiological imaging, including magnetic resonance imaging, computed tomography and bone scan. PMID- 26893736 TI - Radiation-induced expression of IER5 is dose-dependent and not associated with the clinical outcomes of radiotherapy in cervical cancer. AB - This study aimed to investigate the expression of the immediate-early response 5 (IER5) gene in cervical cancer tissues and explore the association between the expression of IER5 and the clinical outcomes of radiotherapy. We collected specimens by surgery or biopsy and obtained 53 specimens from tissues after radiotherapy and 16 specimens from tissues before radiotherapy. Immunohistochemistry and western blotting were used to assess the protein expression levels of IER5. Quantitative polymerase chain reaction (qPCR) was performed to assess the mRNA expression levels of IER5. The protein and mRNA expression levels of IER5 in cervical cancer patients treated with radiation doses >=20 Gy were significantly higher than in those treated with radiation doses <20 Gy (P<0.05) and before treatment with radiotherapy. Moreover, the expression of IER5 was significantly positively correlated with the radiation dose (immunohistochemistry: r=0.548, P=0.019; qPCR: r=0.671, P=0.002; western blotting: r=0.573, P<0.0001). Radiotherapy induced the upregulated expression of IER5 and this was dependent on the radiation dose. However, the radiation-induced expression of IER5 was not associated with the clinical outcomes of radiotherapy in cervical cancer. PMID- 26893737 TI - Diagnosis and management of tumor-like hypophysitis: A retrospective case series. AB - Tumor-like hypophysitis is an uncommon sellar condition that presents as inflammatory lesions on the structures of the pituitary gland. The diagnosis and management of hypophysitis poses a significant challenge, as its clinical manifestation and appearance in imaging studies are difficult to distinguish from that of pituitary tumors. The present retrospective study summarizes two rare cases of primary granulomatous hypophysitis, two cases of lymphocytic hypophysitis, and three cases in which a pathological diagnosis was not determined due to the use of hormone replacement therapy only. The mean age of the patients studied was 45.71+/-22.16 years, and the patients comprised two males and five females. The clinical signs of hypophysitis included headache, fever, gradual decrease in visual acuity, nausea and vomiting. Enhanced magnetic resonance imaging revealed sellar and pituitary stalk lesions, with iso- or hypodense signals on T1-weighted images. Transsphenoidal surgery was performed in three cases. It was challenging to diagnose hypophysitis due to the lack of any significant specific clinical signs. A transsphenoidal biopsy with fast-frozen pathology is able to diagnose hypophysitis. Glucocorticoid therapy may be a potential treatment for hypophysitis, as complete removal of pituitary masses may disable pituitary function. PMID- 26893738 TI - Clinical analysis of 82 cases of carcinoma showing thymus-like differentiation of the thyroid. AB - The aim of the present study was to summarize the clinical characteristics, diagnosis, treatment and prognosis of carcinoma showing thymus-like differentiation of the thyroid (CASTLE). A search of the relevant literature was conducted, which identified 82 cases of CASTLE reported to date. A review of the clinical and auxiliary examination data, treatment, pathological findings and follow-up of these cases was performed. The clinical manifestations of CASTLE varied and did not demonstrate specificity. During ultrasound examination, CASTLE was described as a solid and hypoechoic mass, and the echo was typically observed to be heterogeneous. In computed tomography (CT), CASTLE was demonstrated to be a well-defined, soft tissue density mass without calcification, which appeared enhanced following administration of contrast medium. In emission CT, CASTLE was revealed as a 'cold nodule'. A total of 78 patients underwent radical surgery, and 12 patients experienced recurrence. Lymph node metastasis did not promote recurrence, and postoperative radiation was not able to reduce the recurrence rate (P=0.144 and 1.000, respectively). The median follow-up time was 14 months (range, 1-312 months). Typical immunohistochemical examinations demonstrated the specimens to be positive for cluster of differentiation (CD)5, CD117, cytokeratin 19, epithelial membrane antigen and tumor protein 63, and negative for calcitonin, thyroglobulin and thyroid transcription factor-1. Thyroid CASTLE is a rare malignancy whose exact diagnosis relies on pathological examination, particularly immunohistochemistry, since preoperative examinations are usually unable to provide an exact diagnosis. Radical resection is the primary treatment for CASTLE, which presents favorable prognosis. PMID- 26893739 TI - Heparanase regulates in vitro VEGF-C expression and its clinical significance to pancreatic ductal cell adenocarcinoma. AB - Heparanase (HPSE) and vascular endothelial growth factor C (VEGF-C) are important cytokines that promote metastasis and angiogenesis in numerous malignant neoplasms, however, their association remains unclear in pancreatic ductal cell adenocarcinoma (PDAC). The present study aimed to investigate whether HPSE has a positive correlation with VEGF-C expression and to uncover the role it plays in the in vitro invasion of BxPC-3 cells (a pancreatic carcinoma cell line), and to analyze the value of joint detection of HPSE and VEGF-C for PDAC patients. A recombinant plasmid, GV230/HPSE was constructed and BxPC-3 cells were transiently transfected with GV230/HPSE or siRNA against HPSE. The expression levels of HPSE and VEGF-C were compared using reverse transcription quantitative PCR (RT-qPCR) and immunoblotting. The metastatic potential of treated BxPC-3 cells was evaluated using a Transwell(r) invasion assay. The relative mRNA levels of HPSE and VEGF-C in 34 PDAC specimens were assessed by RT-qPCR. The results of the RT qPCR demonstrated a 10.7- and 3.24-fold elevation (P<0.01) of HPSE mRNA and VEGF C mRNA, respectively, in GV230/HPSE group, whereas the HPSE siRNA group were downregulated for these mRNAs (-2.45-fold, P<0.01; -1.84-fold, P<0.01). The same pattern for protein expression was detected using immunoblot assays. In Transwell(r) invasion assays 138+/-5 cells in GV230/HPSE group and 53+/-4 cells in siRNA group migrated through the Matrigel(r). A negative correlation between the mRNA levels of HPSE and VEGF-C in PDAC specimens and the prognosis factors of the postoperative patients was identified. Spearman rank correlation analysis indicated a positive correlation between HPSE and VEGF-C in PDAC (r=0.812, P<0.01). HPSE regulates the expression of VEGF-C and facilitates invasion of BxPC 3 in vitro. Joint detection of HPSE and VEGF-C may therefore be clinically useful in determining the prognosis of pancreatic cancer patients. PMID- 26893740 TI - A study of the potential anticancer activity of Mangifera zeylanica bark: Evaluation of cytotoxic and apoptotic effects of the hexane extract and bioassay guided fractionation to identify phytochemical constituents. AB - The present study investigated the potential anticancer activity of the bark of Mangifera zeylanica, an endemic plant in Sri Lanka that has been traditionally used for cancer therapy. Cytotoxic and apoptotic effects were investigated in vitro using sulphorodamine assay, acridine orange and ethidium bromide staining, caspase-3 and -7 activity, DNA fragmentation and reverse transcription quantitative polymerase chain reaction in estrogen receptor positive MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines, SKOV-3 ovarian cancer cell line and MCF-10A normal mammary epithelial cells. Hexane extract demonstrated increased levels of cytotoxicity in cancer cells (IC50, 86.6-116.5 ug/ml) compared with normal cells (IC50, 217.2 ug/ml). Chloroform extract demonstrated increased cytotoxicity to normal cells (IC50, 92.9 ug/ml) compared with cancer cells (IC50, 280.1-506.5 ug/ml). Exposure to the hexane extract led to morphological changes characteristic of apoptosis and DNA fragmentation in the three cancer cell lines. Caspase-3 and -7 were significantly activated in MDA-MB 231 and SKOV-3 cells, indicating the occurrence of caspase-dependent apoptosis in these cells, and caspase-independent apoptosis in MCF-7 cells. Furthermore, upregulation of proapoptotic Bcl-2-associated X protein occurred in the three cancer cell lines, and antiapoptotic survivin was downregulated in MCF-7 and SKOV 3 cells; by contrast, tumor protein p53 was upregulated only in MCF-7 cells, suggesting p53-mediated apoptosis in MCF-7 cells and p53-independent apoptosis in the remaining cancerous cell lines. In addition, fraction M1 obtained from bioactivity-guided fractionation of the hexane extract demonstrated increased cytotoxicity in cancer cells (IC50, 15.4-38.7 ug/ml) compared with normal cells (IC50, 114.6 ug/ml), with the highest cytotoxicity observed in MDA-MB-231 triple negative breast cancer cells. The hexane extract of M. zeylanica bark contained polyphenols and flavonoids, and caused free radical scavenging activity. Its gas chromatography-mass spectrometry profile revealed the presence of long-chain hydrocarbons, including beta-sitosterol and beta-amyrin. Fraction M1 contained seven unknown compounds and a small number of known non-cytotoxic compounds. Collectively, results obtained in the present study indicate that the hexane extract of M. zeylanica bark mediates cytotoxic activities through induction of apoptosis in three cancer cell lines; thus, the hexane extract may be used to isolate novel anti-cancer compounds. PMID- 26893741 TI - Clinical correlation of calpain-1 and glypican-3 expression with gallbladder carcinoma. AB - Gallbladder carcinoma (GBC) possesses a poor prognosis, which is primarily attributed to the lack of early and timely surgical intervention. Calpain-1 and glypican-3 have been implicated in the progression of various types of cancer. The present study aimed to detect the expression of calpain-1 and glypican-3 in GBC, and analyzed whether the expression levels of these proteins correlated with any clinicopathological variables. A total of 100 patients with GBC and 30 patients with cholecystitis who accepted surgical treatment were enrolled in the present study. Pathological and clinical data were obtained from all patients. The expression of calpain-1 and glypican-3 was detected in paraffin-embedded tissues by immunohistochemistry. Calpain-1 expression was manually assessed with an immunohistochemical H-score with a slight modification. Glypican-3 expression was assessed as negative and positive. The correlations between protein expression and clinicopathological characteristics, and the associations between the proteins were analyzed. All patients exhibited positive expression of calpain 1. Notably, the high expression rate of calpain-1 was significantly increased in patients with GBC, compared with patients with cholecystitis (32.0 vs. 6.7%; chi2=7.668; P=0.006), suggesting that calpain-1 expression may be associated with progression from cholecystitis to GBC. In addition, the positive rate of glypican 3 expression was 53.0% in patients with GBC and 63.3% in patients with cholecystitis, with no significant difference (chi2=0.997; P=0.318). Furthermore, the expression of calpain-1 and glypican-3 had no significant correlation with gender, age, degree of tumor differentiation and tumor-node-metastasis classification in patients with GBC. Notably, the expression of calpain-1 and glypican-3 displayed a significant positive correlation in patients with GBC (r=0.517; P<0.01), but a significantly negative correlation (r=-0.856; P<0.01) in patients with cholecystitis. In conclusion, calpain-1 expression may be associated with progression from cholecystitis to GBC. Combined detection of calpain-1 and glypican-3 may be beneficial for prognosis assessment of GBC. PMID- 26893743 TI - Analysis of the prognosis of patients with testicular seminoma. AB - Testicular seminoma is a common malignancy, accounting for 35-50% of testicular tumors. Comprehensive therapies lead to good curative efficacy. However, the factors that affect prognosis remain to be elucidated. The aim of the present study was to analyze the 3-, 5- and 10-year survival rate of patients with testicular seminoma as well as the associated factors of prognosis. The clinical data from 58 patients diagnosed with testicular seminoma were collected betweeen January 1999 and January 2014. The survival rate for this group was evaluated using the Kaplan-Meier method. Associated factors of prognosis were analyzed using the log-rank test. The results showed that approximately 62.1% of the cases were in the 30- to 50-year age group. From this age group, 94.8% of patients survived for 3 years, 86.2% for 5 years and 70.7% for 10 years. A significant difference was identified for the different clinical stages, pathological types and postoperative treatment in the 3-, 5- and 10-year survival rates (P<0.05). In conclusion, the clinical stages, pathological types and postoperative treatments significantly affect the prognosis of testicular seminoma. Selection of an appropriate method of treatment including the clinical stages and histological types, is the key element in testicular seminoma therapy. PMID- 26893742 TI - Evaluation of the cytotoxic effects of Cyperus longus extract, fractions and its essential oil on the PC3 and MCF7 cancer cell lines. AB - Cyperus longus is one of the Iranian endemic species. However, to date, and to the best of our knowledge, there are no availale academic reports on the cytotoxicity of this plant. Thus, this study was carried out to examine the in vitro anti-proliferative and anti-apoptotic effects of Cyperus longus extract, fractions and essential oil (EO) on MCF7 and PC3 cell lines. The chemical constituents of EO were identified using gas chromatography (GC)-mass spectrometry (MS) analysis. The cells were cultured in RPMI-1640 medium and incubated with various concentrations of the plant extract and fractions. Cell viability was quantified by MTT assay following 24, 48 and 72 h of exposure to (12.5-200 ug/ml) of the methanol extract, the dichloromethane (CH2Cl2), ethyl acetate (EtOAc) and water fractions, as well as the EO of the plant. The percentage of apoptotic cells was determined using propidium iodide staining of DNA fragments by flow cytometry (sub-G1 peak). The most effective fraction in the MCF7 cell line was the CH2Cl2 fraction (IC50 after 48 h, 25.34+/-2.01). The EtOAc fraction (IC50 after 48 h, 35.2+/-2.69) and the methanol extract (IC50 after 48 h, 64.64+/-1.64) were also found to be effective. The IC50 values obtained for the PC3 cell line were 37.97+/-3.87, 51.57+/-3.87 and 70.33+/-2.36 for the CH2Cl2 fraction, the EtOAc fraction and the methanol extract, respectively. Based on these data and due to the partial polarity of the most effective fraction (the CH2Cl2 fraction), we also examined the cytotoxicity of the plant EO. The IC50 values after 48 h were 22.25+/-4.25 and 12.55+/-3.65 in the PC3 and MCF7 cell lines, respectively. DNA fragmentation assay also confirmed these data. Performing GC-MS analysis for the plant EO revealed that beta-himachalene (10.81%), alpha-caryophyllene oxide (7.6%), irisone (4.78%), beta-caryophyllene oxide (4.36%), humulene oxide (12%), viridiflorol (4.73%), aristolone (6.39%) and longiverbenone (6.04%) were the main constituents. Our results demonstrated that two of the constituents of Cyperus longus, viridiflorol and longiverbenone, should be investigated further as possible promising chemotherapeutic agents in cancer treatment. PMID- 26893744 TI - Mechanism of BMP9 promotes growth of osteosarcoma mediated by the Notch signaling pathway. AB - Bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2, plays a key role in promoting osteosarcoma growth. However, the underlying mechanism remains to be determined. The aim of the present study was to determine the mechanism of BMP9 promoting the growth of osteosarcoma mediated by the Notch signaling pathway. Osteosarcoma cell lines, 143B and MG63, were used for the in vitro experiments. Cell proliferation, cell migration and cell cycle transformation were monitored under various settings. The control and experimental groups used in the present study were BMP9 adenovirus (AdBMP9), a recombinant adenovirus expressing the dominant-negative mutant of Notch1 (AdR dnNotch1), AdBMP9+AdR-dnNotch1 and AdBMP9+compound E (blocker of the Notch signaling pathway). The results showed that Notch ligands DLL1, JAG1 and JAG2, as well as Notch receptors Notch1, Notch2 and Notch3 were markedly expressed in the two cell lines. Cell proliferation and migration ability increased in the AdBMP9 group and were higher than that in the AdBMP9+AdR-dn Notch1 and AdBMP9+compound E group. Cell proliferation and migration in the AdR-dnNothc1 group was lower than that in the AdBMP9 group, although the differences were not statistically significant (P>0.05). The cell cycle ratio in the S/G2 phase increased significantly in the AdBMP9 group and was higher than that in the AdBMP9+AdR dnNotch1 and AdBMP9+compound E groups. By contrast, the ratio of the cell cycle in S/G2 phase in the AdR-dnNotch1 group was lower than that in the AdBMP9 group. The differences were not statistically significant (P>0.05). In conclusion, the results showed that the Notch signaling pathway plays an important role in mediating the growth of osteosarcoma promoted by BMP9. PMID- 26893745 TI - Effects of CIK on hypoxia inducible factor-1alpha and T-cell subsets on colon 26 cancer xenograft mice. AB - Colorectal cancer is a common malignancy of the digestive tract with a high mortality rate. However, current treatment approaches such as radiotherapy and chemotherapy are ineffective. Thus, it is imperative to identify ways to treat recurrence and metastasis. The aim of the present study was to investigate the effects of cytokine-induced killer (CIK) cells on the hypoxia microenvironment and immune function in colon 26 cancer xenograft mice. A murine model of colon 26 carcinoma tumors were divided into CIK, normal saline (NS) and control groups. Hypoxia inducible factor-1alpha (HIF-1alpha) mRNA in tumor tissue and the small intestine of mice was detected by FQ-PCR. The percentage of the CD4+, CD8+ and CD4+/CD8+ ratio in the spleen of mice was detected by flow cytometry. The tumor volume in the CIK group was smaller than that in the NS group and the difference was not significant (P>0.05). HIF-1alpha gene expression was present in the tumor tissue and small intestine. HIF-1alpha gene expression in tumor tissue was significantly higher than that in the small intestine (P<0.05), and lower in tumor tissue of the CIK group compared to the NS group (P<0.05) of xenograft mice. However, no HIF-1alpha expression was observed in the small intestine of healthy control mice. CD4+ T-cell percentage and CD4+/CD8+ ratio in the spleen of xenograft mice was significantly lower than that of normal mice (P<0.05). Compared to the NS group, the CD4+ T-cell percentage was higher, whereas the CD8+ T-cell percentage was lower in the CIK group (P<0.05). In conclusion, HIF-1alpha gene expression was present in the tumor tissue and small intestine. The immune function of colon 26 transplanted in tumor mice was decreased. Additionally, CIK improved the microenvironment of tumor hypoxia and promoted immune reconstitution. PMID- 26893746 TI - High RhoA expression at the tumor front in clinically localized prostate cancer and association with poor tumor differentiation. AB - Ras homolog gene family, member A (RhoA) has been reported as essential to the invasion process and aggressiveness of numerous cancers. However, there are only sparse data on the expression and activity of RhoA in clinically localised prostate cancer. In numerous cancers, tumour cells at the invasive front demonstrate more aggressive behaviour in comparison with the cells in the central regions. In the present study, the expression and activity of RhoA was evaluated in 34 paraffin-embedded and 20 frozen prostate tissue specimens obtained from 45 patients treated with radical prostatectomy for clinically localised cancer. The expression patterns of RhoA were assessed by immunohistochemical staining and western blotting. Additional comparisons were performed between the tumour centre, tumour front and distant peritumoural tissue. RhoA activity was assessed by G-LISA. Associations between RhoA expression and the clinical features and outcome of the patients were also analysed. The present study found an increasing gradient of expression from the centre to the periphery of index tumour foci. RhoA expression was significantly increased at the tumour front compared to the tumour centre, which was determined using immunohistochemistry (P=0.001). Increased RhoA expression was associated with poor tumour differentiation in the tumour front (P=0.044) and tumour centre (P=0.039). Subsequent to a median follow up period of 52 months, the rate of prostate-specific antigen (PSA) relapse was increased in patients with higher RhoA expression at the tumour front when compared with patients with lower RhoA expression (62.5 vs. 35.0%), although the difference was not significant (P=0.09). There was no association between RhoA expression and the PSA level or pathological stage in the present study. In conclusion, RhoA expression was increased at the tumour front and was associated with poor tumour differentiation in the tumour front and tumour centre, indicating the potential role of RhoA in prostate cancer. RhoA expression may also act as a prognostic factor in prostate cancer. The present data provide a foundation for novel therapeutic approaches by targeting RhoA in prostate cancer. PMID- 26893747 TI - Identification of genes and signaling pathways associated with squamous cell carcinoma by bioinformatics analysis. AB - The present study aimed to investigate the genes and signaling pathways associated with squamous cell carcinoma (SCC) by bioinformatics analysis. For this purpose, the GSE2503 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) between 6 normal skin and 5 SCC samples were analyzed using the Linear Models for Microarray Data package. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed, followed by functional annotation and construction of a protein-protein interaction (PPI) network. Subnetwork modules were subsequently identified and analyzed. A total of 181 DEGs, including 95 upregulated and 86 downregulated DEGs, were identified, in addition to 20 GO biological processes terms enriched by upregulated DEGs and 14 enriched by downregulated DEGs. The upregulated DEGs were enriched in 18 pathways, and the downregulated DEGs were enriched in 7 pathways. Following functional annotation, three upregulated transcription factors (TFs), including hypoxia inducible factor 1, alpha subunit (HIF1A), and six downregulated TFs were identified. In the PPI network and subnetwork, matrix metallopeptidase 1 (MMP1), also known as interstitial collagenase, and interleukin 8 (IL8) were the hub genes with the highest degree of connectivity (degree =8). Integrin alpha (ITGA)6 and 2 were enriched in several pathways, including focal adhesion and extracellular matrix-receptor interaction. DEGs of SCC were primarily enriched in pathways associated with cancer and cell adhesion. Therefore, DEGs such as IL8, MMP1, HIF1A, ITGA6 and ITGA2 may be potential targets for the diagnosis and treatment of SCC. PMID- 26893748 TI - Identification of genes and pathways associated with pancreatic ductal adenocarcinoma by bioinformatics analyses. AB - This study aimed to explore the underlying genes and pathways associated with pancreatic ductal adenocarcinoma (PDAC) by bioinformatics analyses. Gene expression profile GSE43795 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between six PDAC and five non neoplastic pancreatic tissue samples were analyzed using the limma package. Gene ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by functional annotation and protein-protein interaction (PPI) network construction. Finally, the sub-network was identified and pathway enrichment analysis was performed on the contained DEGs. A total of 374 downregulated and 559 upregulated DEGs were identified. The downregulated DEGs were enriched in GO terms associated with digestion and transport and pathways related to metabolism, while the upregulated DEGs were enriched in GO terms associated with the cell cycle and mitosis and pathways associated with the occurrence of cancer including the cell cycle pathway. Following functional annotation, the oncogene pituitary tumor transforming 1 (PTTG1) was upregulated. In the PPI network and sub-network, cell division cycle 20 (CDC20) and BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) were hub genes with high connectivity degrees. Additionally, DEGs in the sub-network including cyclin B1 (CCNB1) were mainly enriched in the cell cycle and p53 signaling pathways. In conclusion, the cell cycle and p53 signaling pathways may play significant roles in PDAC, and DEGs including CDC20, BUB1B, CCNB1 and PTTG1 may be potential targets for PDAC diagnosis and treatment. PMID- 26893749 TI - 99mTc-MDP uptake in SPECT/CT by a bladder hernia simulating inguinal metastasis: A case report. AB - A 72-year-old male with a history of prostate cancer and high prostate specific antigen levels underwent 99mtechnetium-methylene diphosphonate (99mTc-MDP) single photon emission computed tomography/computed tomography (SPECT/CT), to identify bone metastasis. The patient possessed no previous history of serious illnesses or surgical procedures and no family history of malignancies. A whole-body CT scan revealed an intense MDP uptake in the right inguinal region on the anterior view, but not in the posterior view, which was suspected to be a metastatic lesion. However, there was no evidence of bone metastasis on the CT scan. In addition, an increased 99mTc-MDP uptake was indicated on the SPECT images in the right inguinal region, which appeared to be separate from the main bladder activity. CT images of the pelvis revealed an inferior tongue-like extension of the bladder into the right inguinal region. Fused SPECT/CT axial images indicated the circular accumulation of the 99mTc-MDP in the medial right groin, with well defined walls that connected the accumulation to the bladder. The final diagnosis was a bladder hernia (T2N0M0), which may have been responsible for the misdiagnosis of bone metastasis due to the use of radiopharmaceuticals (99mTc MDP) that were mainly excreted through urination. Considering the comprehensive situation of the patient, radical prostatectomy was performed. The bladder hernia was subsequently monitored by follow-up examination every 3 months, and remains alive and under follow-up to date. PMID- 26893750 TI - Evaluation of the improved tubeless cutaneous ureterostomy technique following radical cystectomy in cases of invasive bladder cancer complicated by peritoneal metastasis. AB - Radical cystectomy, as the most common surgical treatment for patients with invasive bladder cancer (IBC) complicated by peritoneal metastasis, is usually accompanied by a urinary diversion procedure. In this study, we evaluated the improved tubeless cutaneous ureterostomy technique by comparing the resulting clinical effects with either a traditional ureterostomy and an ileal conduit urinary diversion. Clinical data from 85 patients who underwent 1 of the 3 procedures between April 2012 and April 2015 were analyzed retrospectively. In total, 30 patients underwent improved tubeless cutaneous ureterostomy, 28 patients underwent a traditional cutaneous ureterostomy and 27 underwent an ileal conduit urinary diversion following radical cystectomy. The incidence of complications, including stoma infection, nipple atrophy, terminal necrosis, urine leakage, external orifice stenosis, uronephrosis and ureterectasia in the group of patients treated with the improved tubeless ureterostomy technique was significantly lower than that of the patients in the other 2 groups, and the difference was statistically significant (P<0.05). In addition, the duration of the surgery, intra-operative bleeding, the duration of the hospitalization period and the time to extubation in the patients treated with the improved tubeless ureterostomy technique were significantly decreased (P<0.05) compared with the patients in the other 2 groups. Finally, the health-related quality of life of the patients treated with the improved tubeless ureterostomy technique was significantly higher (P<0.05) than that of the patients in the other 2 groups. The findings of our study demonstrated that the use of the improved tubeless cutaneous ureterostomy technique following radical cystectomy in patients with IBC complicated by peritoneal metastasis resulted in improved clinical effects. Thus, improved tubeless cutaneous ureterostomy may be a promising alternative for enhancing the quality of life of patients with IBC. PMID- 26893752 TI - Effect of hydrothorax EGFR gene mutation and EGFR-TKI targeted therapy on advanced non-small cell lung cancer patients. AB - Lung cancer is a malignancy with the highest incidence of morbidity and mortality worldwide. The lack of effective detection methods leads to the ineffectiveness of convetional therapy. The aim of the current study was to analyze the hydrothorax epidermal growth factor receptor (EGFR) mutation in patients with advanced non-small lung cancer (NSCLC) and malignant pleural effusion. A new method for clinical treatment was developed through a comparison of the difference of EGFR tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy. Between January 2013 and January 2015, 68 cases diagnosed with advanced non-small lung cancer and malignant pleural effusion, were enrolled in the study. Previous first line chemotherapeutic treatment schemes had been unsuccessful. EGFR 19 and EGFR 21 sites were detected for all the patients. Platinum-based drugs were provided for patients with wild-type EGFR. These patients served as the control group and underwent four cycles of treatments, with each cycle lasting 3 weeks. TKI medicine Gefitinib (IressaTM) was administered to patients with mutant EGFR tid, po, for a duration of 4-8 months. These patients served as the experimental group. There were 41 cases of EGFR mutations, of which 13 cases had EGFR 19 site mutations, 16 cases EGFR 21 site mutations, and the remaining 12 cases had 2 site mutations. EGFR mutations were not significant for gender, age, tumor type, stage and diameter (P>0.05). The results showed that the six-month survival rate, progression-free survival time (PFS), objective response rate (RP) and disease control rate (DCR) in the experimental group were higher than those in the control group. The drug side-effects in the experimental group indicated no statistical differences compared to the control group (P>0.05). The incidence of EGFR mutation was higher in patients with advanced non-small lung cancer and malignant pleural effusion. Targeted therapy improved the survival rate and was deemed to be a safe and effective method for patients with EGFR mutations. PMID- 26893751 TI - Expression profiling of selected microRNA signatures in plasma and tissues of Saudi colorectal cancer patients by qPCR. AB - MicroRNAs (miRNAs or miRs) have been advocated as potentially robust and highly stable biomarkers of diverse disease conditions including cancer. The primary aim of this study was two-fold: i) to profile the expression levels of selected mature miRNA signature genes, such as miR-145, miR-195, miR-29 and miR-92, in a paired-study design of 20 colorectal cancer (CRC) tissues from patients versus adjacent neoplasm-free mucosal tissues employing reverse transcription quantitative polymerase chain reaction; and ii) to examine their expression level in the plasma of the same CRC patients in relation to the age-matched plasma of healthy controls. Statistically significant (P<0.01) increases in miR-29 (2.5) and miR-92 (2.6) were observed in CRC tissues compared with adjacent neoplasm free mucosal tissues. Profiling of CRC plasma samples showed that the expression levels of circulating miR-29 and miR-92 were significantly higher (P<0.01) than in the age-matched normal plasma. By contrast, miR-145 and miR-195 exhibited significant (P<0.05) decreases in their mean expression levels in CRC tissue samples in relation to the normal tissues. The mean expression levels of miR-145 and miR-195 were significantly lower (P<0.05) in CRC plasma than the healthy controls. Distinct stage-dependent changes in the expression level of the four miRNA gene profiles were observed between stages II and IV plasma of CRC patients relative to the control plasma. Taken together, the results clearly reflect a similar trend for the four miRNA expression levels in tissue and plasma as well as the positive correlation in the levels of miRNAs in tissues and plasma. These findings may be useful to clarify the molecular mechanisms underlying colorectal carcinogenesis and to underscore the potential of the investigated miRNAs as novel early diagnostic biomarkers of CRC. PMID- 26893753 TI - Juxtaglomerular cell tumor: A case report. AB - The current study reports the case of a 29-year-old female with a long-standing history of hypertension and headaches who presented to the Outpatient Clinic of The Central Hospital of Lishui (Lishui, Zhejiang, China). Abdominal ultrasound and contrast-enhanced computed tomography were performed, which showed a left renal neoplasm, prompting a diagnosis of renal angiomyolipoma or renal cell carcinoma. After a laparoscopic partial nephrectomy was performed, a number of different diagnoses were suggested by several pathologists from eight hospitals. Considering the patient's gender, age, medical history, histopathological features and immunohistochemistry, a final diagnosis of a juxtaglomerular cell tumor (JGCT) was established. The present study therefore indicates that the possibility of a JGCT should be considered when young adults present with renal parenchymatous tumors and high blood pressure. In addition, pathologists must take clinical information into account to form a precise diagnosis. PMID- 26893754 TI - Primary dumbbell-shaped epidural myxoid liposarcoma of the thoracic spine: A case report and review of the literature. AB - Myxoid liposarcoma frequently occurs in the deep soft tissue of the extremities, particularly in the thigh. The present study describes an extremely rare case of primary dumbbell-shaped epidural myxoid liposarcoma of the thoracic spine occurring in a 22-year-old woman. Although preoperative magnetic resonance imaging findings were thought to be compatible with schwannoma, the pathological diagnosis of the resected tumor was myxoid liposarcoma. The patient underwent three courses of adjuvant chemotherapy with doxorubicin and ifosfamide, and exhibited no symptoms or signs of local recurrence or metastasis for 18 months post surgery. The present case suggests that, when radiologically diagnosing spinal epidural tumors, clinicians should consider the possibility of myxoid liposarcoma. PMID- 26893755 TI - A clinicopathological study of atypical leiomyomas: Benign variant leiomyoma or smooth-muscle tumor of uncertain malignant potential. AB - Atypical leiomyomas are histopathologically recognized by moderate to severe pleomorphic atypical tumor cells showing low mitotic counts without coagulative tumor cell necrosis. The histopathological features and clinical behavior of these tumors are unclear. The surgical management of these lesions includes myomectomy and hysterectomy. The current study presents 5 cases of women with atypical leiomyomas that were managed surgically. The clinicopathological characteristics of the patients and recurrences were analyzed. The median age of the patients was 43 years old. While 3 out of 5 patients were treated by hysterectomy (with or without salpingo-oophorectomy), the remaining 2 patients were treated by myomectomy. The median mitotic index was 3 mitotic figures/10 high-power fields. The post-operative course of all patients was uneventful, and there was no evidence of local or distant recurrence in a median follow-up time of 72 months. The treatment of choice for atypical leiomyomas is hysterectomy. However, myomectomy may be an option for fertility sparing cases. A thorough consultation with regard to the uncertain behavior of such tumors and a rigorous follow-up must be offered in such patients. PMID- 26893756 TI - Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement with bland cytological features mimicking desmoid-type fibromatosis: A case report and review of the literature. AB - Here, we present an uncommon case of inflammatory myofibroblastic tumor (IMT) involving the mesentery. The tumor was composed of loosely arranged round-to spindle-shaped tumor cells with amphophilic cytoplasm in an inflammatory and myxoid background. The mitotic activity was low (1 per 50 high-power fields) and the tumor cells lacked cellular atypism. Immunohistochemically, the tumor cells demonstrated strong nuclear membranous staining with anaplastic lymphoma kinase (ALK). In situ hybridization for ALK gene rearrangement revealed a splitting apart of the two signals within the tumor cells. Reverse transcription-polymerase chain reaction revealed that the tumor harbored a ran-binding protein 2 (RANBP2) ALK rearrangement. IMTs are usually characterized by epithelioid-to-round cells featuring increased mitotic activity, occasionally demonstrating unusual tumor cells and more aggressive clinical behavior. To date, 23 IMTs have been reported with RANBP2 and ALK gene rearrangements. However, the present case demonstrated indolent cytological features, leading to a difficulty in differentiating it from desmoid-type fibromatosis. PMID- 26893758 TI - Efficacy of p16 and Ki-67 immunostaining in the detection of squamous intraepithelial lesions in a high-risk HPV group. AB - p16 and Ki-67 immunohistochemistry can be used as an ancillary method for the diagnosis of squamous intraepithelial lesion (SIL) versus atrophic change and atypical squamous metaplasia. The aim of the present study was to evaluate the efficacy of these two immunohistochemical markers in the accurate interpretation of cervical biopsies and correlate this data with human papilloma virus (HPV) infection status. The study included 103 formalin-fixed cervical punch and cone biopsy samples, with corresponding HPV DNA test data. Histopathological staining with hematoxylin and eosin, and immunohistochemical staining for p16 and Ki-67 were reviewed by two pathologists. The positivity of p16 and Ki-67 increased significantly with the severity of the cervical lesion in patients with a high risk-HPV (HR-HPV) infection status (P<0.001). However, there was discordance in the HPV-negative group. Furthermore, concomitant diffuse, strong and block positive staining of p16, and a high Ki-67 index were implicated in high-grade SIL in the HR-HPV group. Thus, the two markers were efficient in advancing the diagnostic accuracy of cervical biopsies in the HR-HPV group; however, application of immunohistochemical results should be carefully considered in the HPV-negative group. PMID- 26893759 TI - Xanthogranulomatous gastritis of the remnant stomach mimicking a malignant tumor: A case report. AB - Xanthogranulomas are known to develop in the gallbladder and kidney. Xanthogranuloma of the stomach is a rare disease, and to the best of our knowledge, only a few cases have been reported to date. The present patient was a 64-year-old man who underwent a wide resection of the stomach following a Billroth-I reconstruction for a gastric ulcer ~40 years prior to the current presentation. Due to tarry stools, a gastrointestinal endoscopy was performed, leading to identification of an ulcerated gastric lesion located at the previous suture line at the lesser curvature of the remnant stomach. This lesion was elevated, appearing to indicate a submucosal tumor. Positron emission tomography revealed uptake of fluorodeoxyglucose radiotracer by the tumor. Although not indicated by the biopsy specimens, a malignant tumor of the remnant stomach was suspected, in the form of a malignant gastrointestinal tumor or remnant gastric cancer. Curative resection of the tumor was successfully performed. Histological examination of the resected specimens revealed xanthogranulomatous inflammation consisting of foamy histiocytes and plasma cells, however, no cancer cells were observed. The tumor was diagnosed as xanthogranulomatous gastritis that mimicked a malignant tumor of the remnant stomach. The present study therefore indicates that inflammatory tumors should be considered in the differential diagnosis of malignant tumors. PMID- 26893760 TI - A modified method for the culture of naturally HPV-infected high-grade cervical intraepithelial neoplasia keratinocytes from human neoplastic cervical biopsies. AB - Few studies on cervical intraepithelial neoplasia (CIN) keratinocyte cultures are available due to the numerous technical and methodological problems associated with the in vitro cultivation of these cells. The present study investigated an applicable and effective method for the in vitro cultivation of high-grade CIN keratinocytes from human neoplastic cervical biopsies. Human neoplastic cervical tissue sections were obtained and digested using type I collagen in order to dissociate the cells. The cells were seeded in tissue culture plastic plates that were coated with rat tail collagen type I and contained modified keratinocyte serum-free medium (K-SFM) supplemented with 5% fetal bovine serum. The medium was replaced with K-SFM on days 3, 5 and 7, respectively. The unattached cells were recovered and the cell viability was determined accurately using the Trypan Blue exclusion method. The expression of keratin 14 (K14), keratin 19 (K19), keratin 17 (K17) and P63 was assayed using immunofluorescence in order to identify the presence of CIN keratinocytes. The present results indicated that the attachment rate of CIN keratinocytes significantly increased between 56.75+/-1.76% on day 3 and 77.09+/-3.55% on day 5, and became relatively stable between days 5 and 7. The cell viability significantly decreased between 83.00+/-0.50% on day 5 and 68.17+/-1.04% on day 7. The passaged CIN keratinocytes maintained the original unequally sized, abnormally shaped morphology and did not undergo differentiation. In addition, the passaged CIN keratinocytes exhibited the same human papilloma virus (HPV) genotype that was detected in the original primary cells. K14 and K19 were expressed in the majority of the normal and CIN keratinocytes, whereas K17 and P63 were expressed only in high-grade CIN keratinocytes. The present study proposes a simple and practical method for rapidly obtaining highly purified naturally HPV-infected high-grade CIN keratinocytes from small neoplastic cervical tissues, and provides an appropriate first medium change time for the primary culture of CIN keratinocytes. PMID- 26893757 TI - Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma. AB - The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Kruppel-like factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%; P=0.025; chi2=5.033) and disease-free survival rate (60.7 vs. 90.9%; P=0.015; chi2=5.897) when compared with OSCC patients with high co-expression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC. PMID- 26893761 TI - Epithelial-mesenchymal interconversions and the regulatory function of the ZEB family during the development and progression of ovarian cancer. AB - This study assessed the role of epithelial-mesenchymal interconversions and the regulatory functions of the ZEB family during the development and progression of ovarian cancer. E-cadherin, vimentin, ZEB1 and ZEB2 were analyzed using immunohistochemistry in a series of ovarian tissues that included normal tissue, benign tumors, borderline tumors, malignant tumors and metastatic lesions. The correlation between E-cadherin and ZEB was analyzed. We also analyzed the association between the expression of the four factors and clinicopathological features in ovarian cancer. The results revealed that E-cadherin was weakly positive in normal ovarian epithelium. Cytoplasmic E-cadherin was significantly increased in benign tumors (P<0.01) and further increased in borderline tumors and ovarian cancers. However, cytoplasmic E-cadherin was markedly reduced in metastatic lesions (P<0.01). Membranous E-cadherin was increased in benign tumors, but decreased progressively in borderline, malignant and metastatic tumor tissues (P<0.05). The expression profile of vimentin was opposite to that of membranous E-cadherin. Membranous E-cadherin was negatively correlated with ZEB2 expression (r=-0.514). Additionally, cytoplasmic E-cadherin, ZEB1 and ZEB2 were associated with the FIGO stage of ovarian cancer. ZEB1 was also correlated with ascitic fluid volume. Our results suggest that epithelial-mesenchymal interconversions are dynamically regulated during the development and progression of ovarian tumors. ZEB2, but not ZEB1, may regulate the expression of membranous E-cadherin during these processes. PMID- 26893762 TI - Coexistence of follicular lymphoma and an unclassifiable myeloproliferative neoplasm in a treatment-naive patient: A case report. AB - Myeloproliferative neoplasms are associated with lymphoproliferative diseases following the administration of cytotoxic drugs or exposure to radiation, but are rare prior to therapy. The present study reports the case of a 61-year-old female with a history of transient ischemic attack. The patient, who presented with a palpable mass in the epitrochlear area of the left arm, was simultaneously diagnosed with follicular lymphoma and an unclassifiable myeloproliferative neoplasm. Excisional lymph node biopsy revealed stage I follicular lymphoma (grade 1). Laboratory findings demonstrated leukocytosis, erythrocytosis, thrombocytosis and decreased erythropoietin. Biopsy of the bone marrow revealed hypercellularity, with predominance of erythroid cells, and large polylobated megakaryocytes with increased mitotic figures, but no evidence of lymphomatous infiltration. The janus kinase 2 V617F mutation was also detected in the cells derived from the bone marrow specimen. Following local excision of the lymph node in the left epitrochlear area, radiation was delivered to the involved field, at a dose of 24 Gy in 12 fractions. The patient was started on hydroxyurea (1 g twice per day, orally) 2 weeks subsequent to radiotherapy, and was administered 500 mg twice per day as maintenance therapy. At the six-month follow-up, the white blood cell count, hemoglobin levels and platelet count had reduced, and the patient was in a healthy condition. A computed tomography scan of the neck, chest and abdomen indicated no abnormalities. To the best of our knowledge, the present study is the first case report of follicular lymphoma coexisting with an unclassifiable myeloproliferative neoplasm in a previously healthy patient. Molecular and genetic studies are required to further evaluate this infrequent disease association. PMID- 26893763 TI - MicroRNA-877 acts as a tumor suppressor by directly targeting eEF2K in renal cell carcinoma. AB - MicroRNAs (miRNAs) are involved in tumorigenesis. However, little is known about their role in renal cell carcinoma (RCC). In the present study, the function of the miRNA miR-877 in RCC was investigated, and its expression levels in blood and paired RCC tissues were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis predicted eukaryotic elongation factor-2 kinase (eEF2K) to be the potential mRNA target of miR-877, which was verified by luciferase assay. The expression levels of eEF2K in RCC tissues were evaluated by western blot analysis and qPCR. The proliferation and migration abilities of RCC cells were measured by MTT and in vitro wound healing assays, respectively. The present results indicated that the expression levels of miR-877 were downregulated in blood and paired RCC tissues, whereas the expression levels of eEF2K were upregulated in RCC tissues. In addition, overexpression of miR-877 and knockdown of eEF2K significantly reduced the proliferation and migration abilities of RCC cells in vitro. Furthermore, miR-877 affected the eEF2K/eEF2 signaling pathway in these cells. In conclusion, the present study has demonstrated that miR-877 suppresses the proliferation and migration abilities of RCC cells by modulating the eEF2K/eEF2 signaling cascade. Therefore, miR-877 may be considered a potential biomarker for the diagnosis of RCC. PMID- 26893764 TI - Aneurysmal bone cyst secondary to a giant cell tumor of the patella: A case report. AB - The patella is an unusual location for primary and metastatic bone tumors to develop. The most frequently encountered primary osteolytic lesions at the patella include giant cell tumors of the bone (GCT), chondroblastoma and aneurysmal bone cysts (ABC). However, the presentation of an ABC originating secondary to a GCT at the patella is rare. The present study describes such a case in a 46-year-old female. The differential diagnosis of the condition was extensive. The patient underwent curettage and the addition of bone cement to fill the defect. Pathological analysis of the resected tissue demonstrated that the lesion was consistent with an ABC forming secondary to a GCT. A 3-month follow-up was completed subsequent to the surgery, with a computed tomography scan demonstrating no evidence of recurrence. However, frequent and continuous observations of the patient following diagnosis are planned in order to evaluate the long-term efficacy of the surgical treatment. To the best of our knowledge, the present study describes the third reported case in the literature of this rare, double synchronous, benign tumor located at the patella. PMID- 26893765 TI - Novel somatic mutations identified by whole-exome sequencing in muscle-invasive transitional cell carcinoma of the bladder. AB - Transitional cell carcinoma (TCC) is the one of the most commonly observed types of cancer globally. The identification of novel disease-associated genes in TCC has had a significant effect on the diagnosis and treatment of bladder cancer; however, there may be a large number of novel genes that have not been identified. In the present study, the exomes of two individuals who were diagnosed with muscle-invasive TCC (MI-TCC) were sequenced to investigate potential variants. Subsequently, following algorithm and filter analysis, Sanger sequencing was used to validate the results of deep sequencing. Immunohistochemistry (IHC) was employed to observe the differences in HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) protein expression between tumor tissues and para-carcinoma tissues. A total of 6 nonsynonymous mutation genes were identified in MI-TCC, identified as copine VII, RNA binding motif protein, X-linked-like 3, acyl-CoA synthetase medium-chain family member 2A, HECW1, zinc finger protein 273 and trichohyalin. Furthermore, 5 cases were identified to possess a HECW1 gene mutation in 61 MI-TCC specimens, and all of these were point mutations located at exon 11 on chromosome 7. The mutation categories of HECW1 had 4 missense mutations and 1 nonsense mutation. IHC revealed that HECW1 protein was expressed at significantly increased levels in MI TCC compared with normal bladder urothelium (P<0.001). The present study provided a novel approach for investigating genetic changes in the MI-TCC exome, and identified the novel mutant gene HECW1, which may possess a significant role in the pathogenesis of TCC. PMID- 26893767 TI - Uterine tumors resembling ovarian sex cord tumors: A case report and literature review. AB - Uterine tumors with ovarian sex cord-like elements are a rarely observed type of uterine body tumor with unknown etiology, and are divided into two groups: Endometrial stromal tumors with sex cord-like elements (ESTSCLEs) and uterine tumors resembling ovarian sex cord tumors (UTROSCTs). While ESTSCLEs are commonly associated with metastasis and recurrence, there is limited data in the relevant literature concerning the behavior of UTROSCTs. However, UTROSCTs are typically benign in nature. Although case numbers are limited, extra-uterine or lymph node metastasis has been reported. Surgical approaches may be altered according to the patient's age and desire for future fertility. Hysterectomies with bilateral salpingo-oopherectomy or hysteroscopic tumor resection are reported to be safe surgical treatment options. However, in the current report, a case of UTROSCT initially misdiagnosed as adenosarcoma following hysteroscopic tumor resection is presented. Staging surgery revealed the precise diagnosis of the tumor using appropriate immunohistochemical evaluations, and led to the discovery of a secondary tumor focus in the myometrium, adjacent to the location of the previously excised tumor. Thus, hysteroscopic resection is questionable as a definitive surgical treatment in patients exhibiting UTROSCT. If hysteroscopic resection is the selected treatment, close follow-up with diagnostic imaging is recommended. PMID- 26893766 TI - Diffuse large B-cell lymphoma in colon confounded by prior history of colorectal cancer: A case report and literature review. AB - A 66-year-old male underwent left hemicolectomy for rectal adenocarcinoma in 2008. Five years later he was admitted to hospital with abdominal pain. A computed tomography scan revealed notable thickening of the middle of the ascending colon wall, and colonoscopy revealed an ulcerofungating mass of 3*3 cm in the cecum and extending to the ascending colon. Under the consideration of cancer recurrence, laparoscopic right hemicolectomy was performed directly. Surgical specimens revealed sheets of large pleomorphic lymphoid cells with nuclei of different sizes, nucleoli and mitotic phases visible in most cells. These tested positive for CD45, CD20 and CD79a diffusely, but negative for CD3, CD5, Bcl-2, Bcl-6 and ALK. The Ki-67 proliferation index was 40%. Epstein-Barr virus in situ hybridization did not reveal any positive signals in any of the tumor cells. Based on these findings, the recurrent tumor was diagnosed as diffuse large B-cell lymphoma. The patient could have avoided surgery and received chemotherapy only; however, the case was confounded by the patient's prior history of colorectal cancer due to the rarity of colon lymphoma following rectal cancer in the same patient. It is therefore essential to investigate carefully and differentiate between potential lesions during routine postoperative colonoscopy following colorectal cancer surgery, as patients may present with rare colon lymphoma, which may be confused with a recurrence of colorectal cancer. PMID- 26893768 TI - Curcumin mediates reversion of HGF-induced epithelial-mesenchymal transition via inhibition of c-Met expression in DU145 cells. AB - The hepatocyte growth factor (HGF)/c-Met signaling pathway results in cancer cell scattering and invasion, and has been reported to participate in several types of cancer, including prostate and colorectal cancer. The downstream phosphorylation cascade of HGF, particularly the mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT signaling pathway, regulates epithelial-mesenchymal transition (EMT). However, the mechanism by which these signaling pathways govern EMT, and whether certain kinases are able to respond to specific EMT effectors, remains to be elucidated. In the present study, an increase in the levels of vimentin, rather than co-regulation of certain EMT marker proteins, was observed in response to HGF-induced EMT in DU145 prostate cancer cells. In addition, it was observed that curcumin abrogated HGF-induced DU145 cell scattering and invasion. Furthermore, curcumin was able to effectively inhibit the HGF-induced increase in the levels of vimentin by downregulating the expression of phosphorylated c-Met, extracellular signal-regulated kinase and Snail. In conclusion, the results of the present study demonstrated that curcumin was able to reverse HGF-induced EMT, possibly by inhibiting c-Met expression in DU145 prostate cancer cells. PMID- 26893769 TI - Treatment and functional result of desmoplastic fibroma with repeated recurrences in the forearm: A case report. AB - Desmoplastic fibroma, alternatively known as aggressive fibromatosis or desmoid tumors, occurs in the form of benign locally aggressive tumors that possess a high rate of recurrence. The forearm bones are rarely involved. The current study presents a case of desmoplastic fibroma in the distal forearm of a 23-year-old man. The tumor was widely resected, and the bone defect was reconstructed using an autologous vascularized fibular graft during the resection procedure. The patient experienced recurrence three times and underwent four resections during the subsequent 3 years following the initial resection. After 10 years of follow up, the patient's functional recovery remains positive. Despite the implication that surgical resection may be involved in the development of aggressive fibromatosis, surgical wide local excision and functional reconstruction were recommended for the treatment of the present patient. PMID- 26893770 TI - Advanced prostatic ductal carcinoma in a patient with a long survival time following a total pelvis exenteration: A case report. AB - Ductal adenocarcinoma of the prostate (DAP) is a rare variant of prostate cancer, and has poorly-identified clinical characteristics. Few cases have been previously reported in Chinese males and DAP is more commonly reported in Caucasian males over 70-years of age. In the present study, a 55-year-old Chinese male patient that demonstrated typical lower urinary tract symptoms and normal prostatic-specific antigen levels underwent a transurethral resection of the prostate. The patient was subsequently diagnosed with DAP. A total pelvis exenteration was then conducted successfully. During the 40-month follow-up, the patient remained progression-free. A review of the literature was conducted in order to assess the clinical course, diagnosis, prognosis and optimal management for DAP. The review indicated that DAP is more likely to demonstrate an aggressive clinical course and an unfavorable prognosis; therefore, once the diagnosis has been confirmed, an aggressive management strategy is recommended for the patient, even in the case of metastatic disease. PMID- 26893771 TI - Reversible posterior leukoencephalopathy syndrome following combinatorial cisplatin and pemetrexed therapy for lung cancer in a normotensive patient: A case report and literature review. AB - Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare neurological syndrome of the brain, causing symptoms such as headaches, seizures, altered mental status and visual disturbances. The condition is predominantly associated with hypertension, eclampsia, renal impairment, cytotoxic drugs, immunosuppressive agents and molecular targeted agents, but the precise underlying mechanism of RPLS is not fully understood. The present study describes the case of a 65-year-old female patient with stage IIA non-small cell lung cancer who received cisplatin/pemetrexed treatment at the Leo W. Jenkins Cancer Center. Following 3 cycles of this therapy, the patient was referred to the Emergency Department of Vidant Medical Center with an altered mental status, subsequently presenting with epileptic seizures, a fever and a headache. A neurological examination revealed generalized hyperreflexia and paraparesis, with extensor posturing of the bilateral lower extremities. The lumbar puncture and electroencephalography results were normal, but cranial computed tomography (CT) scans revealed attenuation abnormalities in the bilateral parietal region and the left occipital lobe, with suspected metastasis. Cranial T2-weighted magnetic resonance imaging (MRI) indicated bilateral regions of increased signal intensity in the occipital, temporal and periventricular white matter. The patient was treated with anticonvulsants, steroids and antihypertensive drugs, recovered gradually from the symptoms and regained full consciousness. However, the patient reported residual weakness, presenting with an Eastern Cooperative Oncology Group score of 3, reflective of an inability to independently perform daily activities and self-care. A brain MRI performed 10 days later demonstrated that the subcortical edema had partially subsided. The patient was discharged on day 15 post-admission. A follow-up cranial CT examination 1 month later indicated a partial resolution of the abnormalities. The present report reviews similar associated cases, and also discusses the clinical features and mechanisms underlying RPLS. Although it is typically reversible, RPLS is a serious and potentially life-threatening adverse condition if left untreated. Early recognition of this condition is crucial for the prompt control of the patient's blood pressure or withdrawal of cytotoxic drugs in order to reverse this syndrome. PMID- 26893772 TI - Pituitary metastasis of choriocarcinoma: A case report. AB - Choriocarcinoma is an aggressive obstetric or gynecological neoplasm with a high malignant potential. It is a form of gestational trophoblastic disease and often secondary to hydatidiform mole, and intrauterine or ectopic pregnancy. Choriocarcinoma has a proclivity to metastasize to the lung, vagina, pelvis or liver in over 50% of patients, which always occurs in the early stage of the disease. With an appropriate amount of chemotherapy, the tumor may be treated effectively. However, pituitary metastasis of choriocarcinoma is extremely rare. To the best of our knowledge, no cases of choriocarcinoma metastasizing to the pituitary have been cited previously. Here, we report a case of choriocarcinoma that presented with pituitary metastasis. PMID- 26893774 TI - The regulation of cancer cell migration by lung cancer cell-derived exosomes through TGF-beta and IL-10. AB - Tumorigenesis has been considered to be as a result of abnormal cell-cell communication. It has been proposed that exosomes act as communicators between tumors and their microenvironment and have been demonstrated to be involved in tumorigenesis and subsequent metastasis. However, the mechanisms underlying the role of exosomes in these processes remains elusive. The present study sought to determine the underlying mechanisms. Using two lung cancer cell lines, it was demonstrated that exosomes derived from metastatic small cell lung cancer cells (NCI-H1688) have greater effects on cancer cell migration, compared with exosomes derived from primary non-small cell lung cancer cells (NCI-H2228). Further characterization of the contents of the exosomes demonstrated that there were increased levels of TGF-beta and IL-10 in exosomes from NCI-H1688 cells compared with exosomes derived from NCI-H2228 cells, in particular under hypoxia. Blockade of TGF-beta and IL-10 with antibodies confirmed that these cytokines were essential for the regulation of cancer cell migration. Taken together, the results of the present study indicated that exosomes derived from cancer cells regulated the cellular migration of tumor cells through TGF-beta and IL-10, which may provide a novel approach for developing therapeutic methods against cancer. PMID- 26893773 TI - Changes in expression of WT1 during induced differentiation of the acute myeloid leukemia cell lines by treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid. AB - The aim of the present study was to investigate the effect of 5-aza-2' deoxycytidine (decitabine; DAC) and all-trans retinoic acid (ATRA) on Wilms' tumor 1 (WT1) in acute myeloid leukemia (AML) in vitro. The methylation status of the WT1 promoter was analyzed using methylation-specific polymerase chain reaction (MSP). The expression level of WT1 was detected by reverse transcription quantitative polymerase chain reaction. The effect of DAC and ATRA on cell differentiation was evaluated by flow cytometry. The WT1 gene was methylated in U937 cells, but unmethylated in SHI-1 and K562 cells; the U937 cells did not express the WT1 gene, but the SHI-1 and K562 cells highly expressed the WT1 gene. DAC and ATRA, alone or in combination, exhibited no effect on the expression level of WT1 in the U937 cells and on the differentiation of the K562 cells. The combined treatment of DAC and ATRA markedly decreased the WT1 expression levels of the SHI-1 and K562 cells, and induced the differentiation of the SHI-1 and U937 cells. In the SHI-1 cells, WT1 expression changed inversely to the dynamic changes of cluster of differentiation 11b-positive rates. In conclusion, the combined treatment of DAC and ATRA has clinical therapeutic potential in acute monocytic leukemia patients with high WT1 expression and a poor response to standard induction chemotherapy. PMID- 26893775 TI - ERbeta overexpression results in endocrine therapy resistance and poor prognosis in postmenopausal ERalpha-positive breast cancer patients. AB - The aim of the present study was to investigate the role of estrogen receptor (ER) beta in the prognosis of ERalpha-positive breast cancer in postmenopausal women, and its effect on the efficacy of endocrine therapy. Tissue specimens from 195 patients with postmenopausal breast cancer were analyzed. ERbeta expression levels were detected using immunohistochemical staining. Kaplan-Meier analysis was performed to assess patient survival, and the difference in survival was analyzed using the log-rank test. Cox regression was utilized to evaluate prognostic factors. The results revealed that the disease-free survival rate decreased dramatically as ERbeta expression levels increased in all postmenopausal ERalpha-positive breast cancer patients, and ERbeta expression was identified to be an indicator of poor prognosis in cases of this disease. Similarly, in postmenopausal ERalpha-positive breast cancer patients undergoing endocrine therapy, high ERbeta expression levels reduced the disease-free survival rate and were correlated with poor patient prognosis. However, in such patients who were not treated with endocrine therapy, disease-free survival rate and prognosis were not significantly affected by ERbeta expression. In conclusion, ERbeta overexpression led to endocrine therapy resistance and poor prognosis in postmenopausal ERalpha-positive breast cancer patients, suggesting that ERbeta may affect breast cancer prognosis via an increase in endocrine therapy resistance. PMID- 26893776 TI - Combined fibrinogen concentration and neutrophil-lymphocyte ratio as a prognostic marker of gastric cancer. AB - Certain patients with early gastric cancer succumb to recurrent disease and cancer-associated complications. The key cause of recurrence is challenging to determine, since clinical blood markers that are able to predict the tumor properties of gastric cancer are limited. The present study investigated the fibrinogen concentration and neutrophil-lymphocyte ratio (NLR) in blood specimens from patients with gastric cancer, and assessed the clinical applicability of combining the fibrinogen concentration with the NLR (CFS-NLR) as a prognostic marker of gastric cancer. The present study consisted of 275 patients with gastric cancer, who were divided into three groups: Those possessing hyperfibrinogenemia (>=305 mg/dl) and a high NLR (>=2.34; CFS-NLR 2 group); those possessing either hyperfibrinogenemia or a high NLR (CFS-NLR 1 group); or those that possessed neither abnormality (CFS-NLR 0 group). The CFS-NLR was significantly associated with the depth of tumor invasion, lymph node metastasis, lymphovascular invasion and tumor stage (P<0.0001). The prognostic differences among the three groups were significant (P=0.0016). Therefore, the CFS-NLR may be a potentially useful blood marker for predicting tumor progression and the prognosis of patients with gastric cancer. PMID- 26893777 TI - Gamma Knife radiosurgery for the treatment of cavernous sinus hemangiomas. AB - The present retrospective study aimed to analyze the outcome of patients with cavernous sinus hemangioma (CSH) treated with Gamma Knife radiosurgery (GKS). Between August 2011 and April 2014, 7 patients with CSHs underwent GKS. GKS was performed as the sole treatment option in 5 patients, whilst partial resection had been performed previously in 1 patient and biopsy had been performed in 1 patient. The mean volume of the tumors at the time of GKS was 12.5+/-10.2 cm3 (range, 5.3-33.2 cm3), and the median prescription of peripheral dose was 14.0 Gy (range, 10.0-15.0 Gy). The mean follow-up period was 20 months (range, 6-40 months). At the last follow-up, the lesion volume had decreased in all patients, and all cranial neuropathies observed prior to GKS had improved. There were no radiation-induced neuropathies or complications during the follow-up period. GKS appears to be an effective and safe treatment modality for the management of CSHs. PMID- 26893778 TI - Downregulation of Foxc2 enhances apoptosis induced by 5-fluorouracil through activation of MAPK and AKT pathways in colorectal cancer. AB - The chemotherapy drug 5-fluorouracil (5-FU) is fundamental for the treatment of colorectal cancer (CRC); however, drug resistance to 5-FU may occasionally occur. Abnormal expression of Forkhead box C2 gene (Foxc2) has been identified in several human cancers, but the role of Foxc2 in the progression of CRC remains unclear. The present study established a stable Foxc2-short hairpin (sh)RNA cell line, which was confirmed by western blot analysis and quantitative polymerase chain reaction. The Foxc2-shRNA cells were treated with 5-FU and the cell viability was determined by an MTT assay. Western blot analysis was performed to investigate the signaling pathway involved in 5-FU treatment. The present study identified that 5-FU increased the percentage of apoptotic CRC cells among the Foxc2/RNA interference-transfected cells compared with cells transfected with an empty vector. Therefore, the downregulation of Foxc2, induced by 5-FU, may enhance apoptosis by the downregulation of apoptotic factors, including B cell lymphoma-2 and pro-caspase-3, in Foxc2-shRNA CRC cells. Furthermore, the mitogen activated protein kinase (MAPK) and phosphatidylinositide 3-kinases/protein kinase B (PI3K/AKT) pathways were essential for the sensitization effect of Foxc2 to 5-FU treatment. Overall, these findings reveal the mechanisms behind Foxc2 depletion and 5-FU treatment of CRC and suggest that Foxc2 enhances resistance to apoptosis, induced by 5-FU, through the activation of MAPK and P13K/AKT pathways, and may serve as a valuable clinical prognostic marker for CRC. PMID- 26893779 TI - Clinical value of prenatal echocardiographic examination in the diagnosis of fetal cardiac tumors. AB - The aim of the present study was to explore the clinical value of prenatal echocardiographic examination in the diagnosis of fetal cardiac tumors. In total, the cases of 8 fetuses with fetal cardiac tumors, which were identified by prenatal ultrasound examination in The First Affiliated Hospital of Nanchang University between January 2012 and January 2014, were retrospectively analyzed. The size, shape, location, activity and hemodynamic changes of the lesions were described in detail, and the patients were followed up. Out of the 8 identified cases of fetal cardiac tumors, 2 fetuses contained tumors only in the left ventricular cavity and 6 fetuses contained tumors of the left and right ventricular cavities, interventricular septum and apex of the heart. Overall, 5 of the 8 female patients requested termination of the pregnancy and labor was induced. The fetuses were pathologically confirmed to possess rhabdomyoma. In addition, 1 patient was followed-up for 5 weeks, and the tumor in the fetal heart cavity was found to have enlarged and developed in multiple regions when follow up was performed. The patient then requested termination of the pregnancy and labor was induced. The fetus was pathologically confirmed to possess rhabdomyoma. The remaining 2 patients insisted on continuation of the pregnancy and the fetuses were followed up during gestation and subsequent to birth by echocardiographic examination. Prenatal echocardiography may precisely position and diagnose occupying lesions of the fetal heart, which is of considerable value in clinical decision making and instruction for treatment. PMID- 26893781 TI - Overexpression of ErbB2 renders breast cancer cells susceptible to 3-BrPA through the increased dissociation of hexokinase II from mitochondrial outer membrane. AB - ErbB2 is known to upregulate glycolysis in breast cancer, however, the precise mechanisms remain unclear. In the present study, ErbB2 upregulated Hexokinase II (HK II) activity by increasing the binding of HK II to the mitochondrial outer membrane. Dysregulated glucose metabolism in high ErbB2-expressing breast cancer cells induces susceptibility to glucose starvation and glycolysis inhibition. Additionally, HK II has a tendency to dissociate from the mitochondria outer membrane in ErbB2-overexpressing cells following treatment with the HK II inhibitor, 3-BrPA. Furthermore, 3-BrPA treatment results in decreased mitochondria membrane potential and release of cytochrome c into cytoplasm in ErbB2-overexpressing cells, leading to activation of the mitochondrial apoptotic signaling pathway. In summary, the results demonstrate a novel mechanism for ErbB2-activated glycolysis and reveal that 3-BrPA is effective in reducing ErbB2 positive breast cancer cell viability by targeting HK II in vitro and in vivo. PMID- 26893780 TI - Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer. AB - An elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with the pathological response to neoadjuvant therapies in numerous types of cancer. The aim of the current study was to clarify the association between pre-treatment NLR and the pathological response to preoperative chemoradiotherapy in pancreatic cancer patients. This retrospective analysis included data from 56 consecutive patients whose tumors were completely surgically resected. All patients received preoperative therapy, consisting of gemcitabine-based chemotherapy (alone or in combination with S-1) combined with 40 or 50.4 Gy irradiation, prior to surgery. Predictive factors, including NLR, platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score and prognostic nutrition index, were measured prior to treatment. A comparison was made between those who responded well pathologically (good response group, Evans classification IIb/III) and those with a poor response (Evans I/IIa). NLR was determined to be significantly higher in the poor response group. Multivariate analysis identified an elevated NLR as an independent risk factor for the poor pathological response [odds ratio (OR), 5.35; P=0.0257]. The pre-treatment NLR (>=2.2/<2.2) was found to be a statistically significant predictive indicator of pathological response (P=0.00699). The results demonstrate that pre-treatment NLR may be a useful predictive marker for the pathological response to preoperative therapy in pancreatic cancer patients. PMID- 26893782 TI - Clinical significance of microRNA-155 expression in hepatocellular carcinoma. AB - The present study aimed to evaluate the expression of microRNA-155 (miR-155) in hepatocellular carcinoma (HCC) and adjacent normal tissues, and assess its correlation with clinicopathological characteristics of this tumor type. miR-155 expression was detected in 40 HCC tissue samples and 40 samples of adjacent tumor free tissue using fluorescent reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The association between miR-155 expression, clinicopathological features and 1-year relapse-free survival (RFS) in HCC and adjacent normal tissue samples was analyzed. RT-qPCR results revealed that, in 25 cases (62.5%), miR-155 expression levels were significantly increased in HCC tissues compared with the expression levels observed in pericarcinomatous tissues (P<0.05). miR-155 expression was observed to be significantly correlated with vessel invasion, Edmonson classification and clinical stage (P<0.05). However, miR-155 expression was not significantly correlated with gender, age, tumor size, tumor number, hepatitis B virus DNA copy number, cirrhosis or concentration of alpha-fetoprotein (P>0.05). A positive correlation was observed between late TNM classification of malignant tumor stage and 1-year RFS (P<0.05). Patients exhibiting high miR-155 expression levels were observed to exhibit a lower 1-year RFS than that of patients with reduced expression of miR-155 (48 vs. 73.3%), however this difference was not statistically significant (P=0.105). Additionally, correlations were observed between miR-155 expression and reduced differentiation, increased invasiveness and late stages of HCC. The current results demonstrated that miR-155 may be involved in the tumorigenesis of HCC and may be associated with clinical characteristics of HCC patients. Additional studies are required to clarify the mechanism of miR-155. PMID- 26893783 TI - Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma. AB - Approved by the Food and Drug Administration in 2011, the anti-cytotoxic T lymphocyte-associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of >=3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in "real world" settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression-free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune-related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre-treatment factor independently predicted toxicity. The number of infusions (4 vs. <=3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long-term vigilance. PMID- 26893784 TI - Multiple malignant inflammatory myofibroblastic tumors of the jejunum: A case report and literature review. AB - Inflammatory myofibroblastic tumors (IMTs) are rare neoplastic lesions with a tendency for locally aggressive behavior and recurrence. IMTs most frequently occur in the soft tissues of children and young adults, with the lungs being the most commonly affected site; however, it has been recognized that any anatomical location may be involved. IMT in the jejunum is extremely rare, with only one case previously reported in the literature. The current study describes the case of a 42-year-old woman presenting with intermittent abdominal pain and small bowel intussusception that was identified during a laparotomy. Surgical resection of the jejunum, revealing 3 exophytic tumors, provided specimens for analysis. Following histological examination, a diagnosis of IMT was made. A review of the literature regarding this rare disease is also presented to emphasize the risk of local recurrence and the importance of adequate long-term follow-up. PMID- 26893785 TI - Rare occurrence of cavitation of lung metastases following effective targeted therapy: A case report. AB - The metastasis of malignant tumors to the lung is relatively common; however, cavitation of metastases is extremely rare in clinical cases, and the various mechanisms are controversial. The majority of irregular metastatic cavities form naturally and are detected incidentally when patients are examined prior to any therapeutic measures. The current study presents the case of a lung adenocarcinoma patient with total cavitation of intrapulmonary metastases following effective targeted therapy at the First Affiliated Hospital of Nanjing Medical University. The morphological changes were followed up for three years. This patient presented thin-walled and smooth clean cavities, which provides an indication of the effectiveness of treatment. PMID- 26893787 TI - Serious neutropenia following neoadjuvant chemotherapy for locally advanced breast cancer: A case report. AB - Neoadjuvant chemotherapy has been widely used in patients with locally advanced breast cancer (LABC) to increase the chance of breast conservation. Among the most active adjuvant chemotherapy regimens, doxorubicin and cyclophosphamide are the most common drugs used for breast cancer in adjuvant and advanced settings, and taxanes are added to neoadjuvant regimens to improve the pathological complete response rates. However, chemotherapy is often associated with a variety of acute and long-term side effects, and neutropenia is one of the most common chemotherapy-associated toxicities. Lethal neutropenia is rarely reported in clinics. The present study reports the case of a patient with LABC that received 1 cycle of neoadjuvant chemotherapy [intravenous docetaxel (75 mg/m2), pirarubicin (45 mg/m2) and cyclophosphamide (500 mg/m2) on day 2 in 3-weekly intervals] and succumbed to neutropenia and subsequent multiple organ dysfunction syndrome. The present study suggests that neutropenia may be associated with significant mortality if not managed appropriately. Based on the findings of the present study, individual chemotherapy regimens, dosing schedules, effective methods of the prevention and management of neutropenia, and the management of the discharged patient require additional consideration. PMID- 26893786 TI - MicroRNA-26a induces osteosarcoma cell growth and metastasis via the Wnt/beta catenin pathway. AB - MicroRNAs (miRNAs/miRs) are a type of highly conserved, small non-coding RNA that are vital to the post-transcriptional regulation of gene expression via base pairing with target mRNA 3'-untranslated regions (3'-UTRs). Several studies have indicated that the abnormal expression of miRNAs occurs frequently in human osteosarcoma (OS). In the present study, the role of miR-26a in the progression and metastasis of OS was investigated using reverse transcription-quantitative polymerase chain reaction, a luciferase activity assay, cell viability assay, in vitro migration and invasion assays, transfection and western blot analysis. miR 26a was upregulated in OS tissues and cell lines, and the expression of miR-26a was indicated to affect the proliferation, migration and invasion of OS Saos-2 cells. At the molecular level, the results showed that glycogen synthase kinase 3beta (GSK-3beta) was identified as a target of miR-26a, and the ectopic expression of miR-26a inhibited GSK-3beta by directly binding to the 3'-UTR. Therefore, the expression of miR-26a was negatively correlated with GSK-3beta in the OS tissues. These data suggest that miR-26a is significant in the proliferation of human OS cells due to the direct regulation of Wnt/beta-catenin signaling. PMID- 26893788 TI - Mediastinal lymph node metastasis of renal cell carcinoma: A case report. AB - Renal cell carcinoma (RCC) may metastasize to mediastinal lymph nodes without any abdominal lymph node involvement. The present study describes an autopsy-proven case of RCC presenting with a large mediastinal mass; the case had been previously misdiagnosed as small cell lung carcinoma due to imaging analysis results, an elevated serum level of neuron-specific enolase and the presence of small atypical cells with a high nuclear/cytoplasmic ratio. Despite RCC occurrence being rare, it should be considered in the differential diagnosis, particularly when a mass located in the kidneys presents with metastases to the mediastinal lymph nodes, even if there is no involvement of the abdominal lymph nodes and the primary lesion is of a small size. PMID- 26893789 TI - Myeloid cell leukemia-1 is a molecular indicator for malignant transformation of oral lichen planus. AB - Oral lichen planus (OLP), characterized by a chronic mucocutaneous inflammatory condition, is a common disease of the oral cavity. Retrospective and prospective epidemiological data suggest that OLP is considered to have malignant potential. However, it is unclear as to which types of molecules may cause malignant transformation of OLP. In the present study, the presence of myeloid cell leukemia-1 (Mcl-1) and B-cell lymphoma-2 (Bcl-2) was studied by western blot analysis in 11 OLP and three normal oral mucosa (NOM) samples and in two human oral cancer cell lines. The functional role of Mcl-1 in oral cancer cells was analyzed using a trypan blue exclusion assay and soft agar assay. Mcl-1 was strongly expressed in the OLP and the two oral cancer cell lines compared with NOM, whereas Bcl-2 was not. Sorafenib and mithramycin A decreased cell viability in MC-3 and HSC-3 oral cancer cells and at same concentration they reduced the expression level of Mcl-1 in the two cell lines. The two chemicals affected Mcl-1 protein and significantly inhibited neoplastic cell transformation in the two cell lines. We suggest that the malignant potential of OLP may be associated with the expression of Mcl-1, and that downregulation of Mcl-1 may prevent malignant transformation of OLP to oral cancer. PMID- 26893791 TI - A Measure to Target Antipoverty Policies in the European Union Regions. AB - The reformed cohesion policy (CP), which is the major investment tool in the European Union (EU) for delivering the Europe 2020 targets, will soon make available substantial funds to improve the quality of life of the EU citizens through supporting the economic and social development of the EU's regions and cities. Because the reformed CP has intensified the emphasis on measuring results, also with respect to reducing poverty and social exclusion, this paper is about measuring poverty to better target EU local policies. We propose a measurement of poverty at the sub-national level in the EU by means of three poverty components describing absolute poverty, relative poverty and earnings and incomes. The core data source is the cross-sectional European Statistics on Income and Living Conditions (EU-SILC) micro-data, waves 2007-2009. Data reliability at the sub-national level is statistically assessed and the regional level is described whenever possible. To calculate the poverty components, an inequality-adverse type of aggregation is applied in order to limit compensability across indicators populating a component. No aggregation is, however, performed across the three components. In the computations of income related indicators, individual disposable income adjusted for housing costs, used as a proxy for the costs of living, is used. Poverty is confirmed to be a multi faceted phenomenon with clear within-country variability. This variation depends on the type of region likely linked to the urbanisation level and, consequently, to the costs of living. The proposed measure may serve to better target anti poverty measures at the local, sub-national level in the EU. PMID- 26893792 TI - Pneumocephalus and Pneumorrhachis After Spinal Surgery. AB - BACKGROUND: Pneumocephalus and pneumorrhachis are rare complications of neurosurgery. When a closed system such as the head and spinal area get injuried, it becomes open and the air can come in through that opening. In this case, we present a case of pneumocephalus and pneumorrhachis after spinal fusion surgery. CASE REPORT: Herein we present a case of diagnosis and treatment of pneumocephalus and pneumorrhachis after spinal fusion surgery. CONCLUSIONS: Our patient developed postoperative pneumocephalus and pneumorrhachis as a late complication secondary to an infection. We wanted it to be considered as an important problem. PMID- 26893793 TI - Doppler Ultrasound and Magnetic Resonance Imaging Findings of Penile Mondor's Disease: Case Report and Literature Review. AB - BACKGROUND: Penile involvement is a rare, self-limiting, benign genital condition. In Mondor's disease the underlying pathology is thrombophlebitis of a superficial vein. CASE REPORT: In this case report, we want to present a rare Penile Mondor's disease with literature review. CONCLUSIONS: While the diagnosis can be based on history, physical examination and Doppler ultrasound, the necessity of both MRI, MR angiography and intracavernosal vasoactive agent administration can be questioned. Both MRI and intravenous vasoactive agent administration may be helpful in suspicious cases for differential diagnosis and to eliminate other etiologies like pelvic mass or thrombosis. PMID- 26893794 TI - A Rare Case of Polyorchidism: Four Testes. AB - BACKGROUND: Polyorchidism or supernumerary testis means more than two testes. It is very rare and to the best of our knowledge, there have been only about 200 cases reported. CASE REPORT: In this case report we want to present radiological features and assessment of a patient with four testicles. CONCLUSIONS: If the vascularity and echogenicity of the scrotal mass is similar with the normal testis parenchyma, multitestis should be considered. The MRI might not provide us with additional information to USG or CDUSG, thus it is not necessary to perform it if there is no suspicion of malignancy. PMID- 26893795 TI - Gastrointestinal stromal tumor of the anal wall in a Nigerian. AB - Documented reports of gastrointestinal stromal tumors (GIST) are relatively few in the sub-Saharan continent. The body of evidence points towards anal wall involvement being a rarity indeed. In this article we document a 61 year old Nigerian man who presented with bleeding per rectum and in whom the histological features (including immunohistochemistry) of the biopsied anal lesion was GIST. PMID- 26893796 TI - [Bacteriological characteristics of the peritoneal dialysis fluid infections]. PMID- 26893797 TI - Measles outbreak in a poorly vaccinated region in Cameroon: a case series study, public health challenges and recommendations. AB - Measles is a highly contagious viral infection and still a leading cause of vaccine-preventable deaths in Africa; especially in unvaccinated populations. We reviewed the medical reports of the measles outbreak that occurred in Misaje, in the North west region of Cameroon from 11/03/2015 to 14/05/2015. Six measles cases were recorded during this period; three of them complicated by bacterial infections. Measles should be considered as a differential diagnosis for any febrile rash especially among poorly vaccinated populations. Primary preventive methods implemented by clinicians could help control outbreaks; especially with delays in public health intervention. Also, gaps in health policies in Cameroon should be addressed to scale up vaccination coverage in remote communities like Misaje to reduce the incidence of measles outbreaks. PMID- 26893798 TI - [Percutaneous cystostomy with Kelly clamp: indications, technique and results]. PMID- 26893800 TI - [Hydatid cyst of the pancreas revealed by acute pancreatitis: report of a case]. PMID- 26893799 TI - [Interest in visual inspection with acetic acid and Lugol iodine with colposcope in screening of cervical lesions in Gabon]. PMID- 26893801 TI - Cardiac metastasis from a renal cell carcinoma. AB - Here we report a case of asymptomatic right ventricular tumor, for which surgical removal was done. Pathology reveals that the mass is a metastasis of a renal carcinoma. PMID- 26893802 TI - [Exophthalmos of the left eye in favor of orbital adenoid cystic carcinoma: report of a case]. PMID- 26893803 TI - [A case of spinal cord atrophy in a professional diver]. PMID- 26893804 TI - [Bilateral hypertrophy of Wharton duct revealing Sjogren syndrome]. PMID- 26893805 TI - [Ramsay Hunt syndrome]. PMID- 26893806 TI - Histomorphometric study of brachiocephalic artery of Japanese quail. AB - Brachiocephalic arteries in quails are large arteries which are arising separately from the aortic arch. The aim of the present study was to determine the histomorphometric aspects of brachiocephalic arteries in the Japanese quail. The different layers of the brachiocephalic artery were studied quantitatively in 10, 20 and 60 days-old Japanese quail; (n = 6) and both sexes. Luminal diameter, thickness of the intima, media and adventitia, the percentage of the intima, media and adventitia, as compared with the total wall thickness were determined. It was found that luminal diameter and whole artery thickness increased by age (p < 0.05). In addition, the tunica media was the thickest layer, then tunica intima and at last tunica adventitia (p < 0.05). The muscularity of the right brachiocephalic artery was more than that of the left one (p < 0.05). Histomorphometric study of brachiocephalic arteries of Japanese quails showed that increasing of age causes increase of internal and external diameters of the artery and this increase in females was more than males. PMID- 26893808 TI - Detection of Arctic and European cluster of canine distemper virus in north and center of Iran. AB - Canine distemper virus (CDV) creates a very contagious viral multi-systemic canine distemper (CD) disease that affects most species of Carnivora order. The virus is genetically heterogeneous, particularly in section of the hemagglutinin (H) gene. Sequence analysis of the H gene can be useful to investigate distinction of various lineages related to geographical distribution and CDV molecular epidemiology. Since vaccination program is conducted only in large cities of Iran, CD still remains as one of the major causes of death in dogs in this country. In order to monitor H gene, CDV has been detected in 14 out of 19 sampled dogs through the amplification of nucleoprotein (NP) gene in nested-PCR assay. In the next step 665 bp of H gene was amplified in 9 out of 14 NP-gene positive dogs. Phylogenetic analysis distinguished two distinct CDV genotypes in Iran. JN941238 has been embedded in European cluster and JN941239 has been embedded in Arctic cluster. Nucleic analysis has been shown high difference among both Iranian CDV lineages with CDV vaccine strains. PMID- 26893807 TI - Synbiotic enhances immune responses against infectious bronchitis, infectious bursal disease, Newcastle disease and avian influenza in broiler chickens. AB - Increased susceptibility of birds to avian pathogens in intensive husbandry system has emphasized on necessity of improvement of innate and specific immune responses of birds by the fast establishment of a beneficial microflora and immune stimulator factors to guarantee healthy and low-price products. During this study, 192 one-day-old broiler chicks (Ross-380) in four groups with three replicates per group were used to investigate effectiveness of synbiotic Biomin Imbo on immune responses of the chickens following routine vaccination against Newcastle disease (ND), avian influenza (AI), infectious bronchitis (IB) and infectious bursal disease (IBD). The results of this study indicated that supplementation of Biomin Imbo in diet enhanced humoral immune responses significantly in the case of ND, IB, IBD (p = 0.049, p = 0.020, p = 0.036, respectively), but insignificantly in the case of AI (p = 0.160) following vaccination of the chickens against these most common important viral poultry diseases. It was more effective following vaccination with live than killed vaccines. In conclusion, application of synbiotic Biomin Imbo, as a feed-additive adjuvant promotes acquired humoral immune responses of broiler chickens. PMID- 26893810 TI - Copper and zinc concentrations in uterine fluid and blood serum during the estrous cycle and pre-pubertal phase in water buffaloes. AB - To investigate uterine fluid and serum copper (Cu) and zinc (Zn) variations during the estrous cycle in water buffaloes, 71 genital tracts and blood samples were collected from the abattoir in Urmia, Iran. The phase of the estrous cycle was determined by examining ovarian structures; 18, 15, 16 and 22 were pro estrous, estrous, met-estrous and diestrous, respectively. The uterine fluid was collected by gentle scraping of the uterine mucosa with a curette. Blood serum and uterine fluid samples of 71 pre-pubertal buffalo calves were also collected and treated in similar manners. The mean (+/- SEM) total serum (77.10 +/- 1.50 ug dL(-1)) and uterine fluid (296.40 +/- 9.40 MUg dL(-1)) Cu in cyclic cows was higher than the values of 54.00 +/- 1.10 MUg dL(-1) and 133.40 +/- 5.70 MUg dL( 1) in pre-pubertal calves, respectively. Blood serum (114.60 +/- 3.20 MUg dL(-1)) and the uterine fluid (349.90 +/- 8.90 MUg dL(-1)) Zn content in cyclic cows were also higher than those (98.80 +/- 1.50 MUg dL(-1) and 246.6 +/- 4.50 MUg dL(-1) respectively) in pre-pubertal calves. Serum Cu in pro-estrus and estrus were lower than those in other stages and also lower than those in the uterine fluid. The lowest serum Zn content was recorded in pro- and met-estrus, while in the uterine fluid it was observed in estrus. In all stages of estrous cycle the uterine fluid Zn content was significantly higher than those of the serum. These results suggested that during the estrous cycle in the buffalo cows, Cu and Zn were actively secreted in uterine lumen and were not dependent on blood serum. The values also increased after puberty. PMID- 26893809 TI - Effects of tail fat on recovery times of anesthesia with isoflurane in fat-tailed Iranian Lori-Bakhtiyari lambs. AB - In the present study, the effect of tail fat on recovery times in intact sheep and sheep with a ligated median sacral artery following similar anesthetic exposure with isoflurane was investigated. This study was performed using seven healthy fat-tailed Iranian Lori-Bakhtiyari ewe lambs. The lambs were anesthetized twice at two week intervals (the experiment was performed in two stages). After mask induction with isoflurane in 100% oxygen, sheep were intubated and anesthesia was maintained for 4 hr using a rebreathing system. Induction and extubation times and time to sternal recumbency and attempts to stand were recorded during anesthetic induction and recovery (Stage 1). Two weeks later, prior to the second anesthesia, the median sacral artery (MSA) was ligated under epidural anesthesia in sheep. All sheep were anesthetized as mentioned above (Stage 2). No significant differences were observed for the induction time between two stages (p > 0.05) but extubation, sternal recumbency and attempts to stand times were significantly longer in intact sheep (Stage 1) after 4 hr anesthesia with isoflurane (p < 0.05). Recovery time was decreased following MSA ligation in fat-tailed sheep, which suggested that body fat had a major role in the recovery time of isoflurane in sheep. We developed an animal model to investigate fat drug solubility of isoflurane gas. Therefore, using less-soluble in fat anesthetics is better than high-soluble anesthetics for prolonged anesthesia to decrease postoperative complication in obese patient. PMID- 26893811 TI - Mercury concentrations in common carp (Cyprinus carpio) tissues, sediment and water from fish farm along the Karoun River in Iran. AB - The Karoun River is major source of water for warm?water fish culture industry in southwest of Iran. The aim of the present study was to investigate the distribution of mercury in tissues of marketable common carp and in bottom sediments of fish farms in Khouzestan province. This study was carried out on 45 fish farms that are located on the bank of the Karoun River in Khouzestan province, south-west Iran. Concentration of mercury (Hg) was determined using spectrophotometery in three tissues (muscles, liver and gills) of farmed common carp (Cyprinus carpio), water and bottom sediments of fish farms collected from three regions (North, center and south) of the Karoun River, in Khouzestan province, Iran. The concentrations of Hg in muscle tissue (2.71 mg kg(-1) dry matter) of fish from the south were significantly higher (p < 0.05) than from the other two sites. In the center and south sampling zones, Hg concentration in muscle was found to be above the maximum tolerable values provided by Food and Drug Administration standards. The Hg concentration of fish farm sediment and water samples were ranged as 0.46 to 0.48 mg kg(-1) dry matter and 3.10 to 4.11 MUg Hg L(-1), respectively. Finally, Hg concentrations at downstream site were higher than upstream site. PMID- 26893812 TI - Prevalence of Listeria monocytogenes in raw milk in Kerman, Iran. AB - Listeria monocytogenes as one of the most important pathogen in public health concerns is transmitted through consumption of contaminated food. The pathogen has been considered as a potential source of contamination of raw milk and dairy products. This research was aimed to investigate prevalence of L. monocytogenes in raw milk in Kerman region. In the summer of 2011, a total number of one hundred raw milk samples were collected from bulk tanks of some dairy farms and tested for iap and actA genes using polymerase chain reaction. Among the 100 samples, five isolates (5.0%) were detected as L. monocytogenes based on phenotypic and genotypic characteristics. Considering the low frequency of L. monocytogenes in this study, raw milk cannot be omitted as a potential source of food contamination for the population of the region. To achieve more accurate isolation, identification and control of L. monocytogenes in raw milk, it is suggested that new standard laboratory methods be implemented as well as biosafety outreach programs, management techniques and education. PMID- 26893813 TI - The effect of the hexanic extracts of fig (Ficus carica) and olive (Olea europaea) fruit and nanoparticles of selenium on the immunogenicity of the inactivated avian influenza virus subtype H9N2. AB - Influenza is a contagious viral disease that is seen in avian, human and other mammals, so its control is important. Vaccination against influenza virus subtype H9N2 is one of the ways in controlling program, for this reason several vaccines has been produced. Recently, application of inactivated oil-emulsion vaccines in poultry for controlling low pathogenic avian influenza is increasing. At present, oils that are used as adjuvant in commercial vaccines are mineral oils, which not only lack immunizing effect, but also produce some detriments. The aim of this study is the evaluation the immunogenicity of vegetable oils, which are more metabolizable and safer than mineral oils. In this study the efficacy of hexanic extracts of fig (Ficus carica) and olive (Olea europaea) fruit and also nano selenium on the immunogenicity of the inactivated avian influenza virus subtype H9N2 was evaluated in broiler chickens. The results indicated that the prepared emulsions could elicit a little degree of immunity, but they could not inhibit the anamnestic response and infection. With regard to the results, it seems that the intact mixture of fig and olive fruit hexanic extracts could not be administered as an immunoadjuvant in the vaccine, and about nano-selenium. In spite of positive effect on the immunogenicity of avian influenza virus subtype H9N2, it still needs more work. PMID- 26893815 TI - Effects of mannan oligosaccharide supplementation on growth, some immune responses and gut lactic acid bacteria of common carp (Cyprinus Carpio) fingerlings. AB - This study was conducted to determine the effects of mannan oligosaccharide (MOS) on growth, some immune responses and gut lactic acid bacteria of common carp. Four experimental diets containing 0%, 0.05%, 0.10% and 0.20% MOS were prepared. Each diet was randomly allocated to triplicate groups of fish with initial average weight of approximately 14 g. After eight weeks, survival rate was high in all treatments with no significant difference (p > 0.05). Growth performance including final weight, weight gain (WG) and specific growth rate (SGR) did not differ among the treatments. Feed conversion ratio (FCR) was better when the fish were fed 0.05 to 0.20% MOS diets. The alternative complement activity, lysozyme activity and serum total Ig were found to be significantly (p < 0.05) greater in fish fed 0.20% MOS diets. Although the total intestinal bacterial counts were not affected by dietary treatment (p > 0.05), the lactic acid bacteria levels were significantly elevated in fish fed MOS diets (p < 0.05). These results indicated that oral administration of MOS at 0.20% elevated the immune response, improved FCR and modulated intestinal microbiota of common carp. PMID- 26893814 TI - Effects of essential oil of Satureja khuzestanica on the oxidative stress in experimental hyperthyroid male rat. AB - This work analyzes the effects of Satureja khuzestanica essential oil (SKEO) on the thyroid and antioxidant system, assessed by measuring levels of tri iodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx) activity. Forty adult male Sprague Dawley rats (225 +/- 25 g) were divided into five equal groups: one control and four hyperthyroid groups that received placebo, 200 mg kg(-1) body weight of vitamin (Vit.) E, 225 mg kg(-1) body weight of SKEO, 200 and 225 mg kg(-1) body weight of Vit. E and SKEO together, respectively. Hyperthyroidism was induced by administering of L-thyroxin in drinking water. After 30 days of L-thyroxin consumption, serum T3 and T4 levels, TSH, and oxidative stress indices were determined. Significant increase in serum T3, T4 and MDA concentrations with a simultaneous significant decrease in TSH, GSH level and GPx activity were observed in hyperthyroid group (p <0.05). In the treatment groups, SKEO and/or Vit. E can compensate serum MDA elevation and GPx activity reduction. Only, SKEO + Vit. E could compensate the decline of GSH levels in response to hyperthyroidism. Supplementation of SKEO, plus Vit. E as antioxidants is useful in attenuating lipid peroxidation and may potentially benefit hyperthyroid patients. PMID- 26893816 TI - Serological study of small ruminant lentiviruses in sheep population of Khorasan e-Razavi province in Iran. AB - Maedi-Visna (MV) virus and caprine arthritis encephalitis (CAE) virus known as small ruminant lentiviruses (SRLVs) cause chronic diseases in susceptible animals. The main reservoirs of these viral agents are sheep and goat. In sheep, MV virus causes a disease as the same name of the virus. This is the first seroprevalence survey of SRLVs in sheep population of Khorasan-e-Razavi province in Iran. Two hundred and twenty sheep from 30 flocks in 12 regions of the province were selected by random cluster sampling method. Serum samples were analyzed for the presence of antibodies against MV/CAE viruses. The seroprevalence in sheep was 34.5% (95.0% CI: 28.3 to 40.7%). Totally, the seroprevalence was in the range of 6.7 to 72.2 %. In 26 flocks of sheep (89.6%; 95.0%CI: 74.4 to 98.8%), at least one seropositive case was detected. The relationship between seropositivity and age, sex, flock size and breeds of sheep were statistically analyzed. In logistic regression model, only age was correlated with SRLV seroprevalence (p < 0.05). This study showed relatively high seroprevalence against SRLVs in sheep population in this area of the country. Due to difficulty in clinical diagnosis, chronic course of the disease, the absence of effective vaccine and treatment and huge economic loss, more epidemiological studies with regards to prevention and control of the disease are necessary. PMID- 26893818 TI - Congenital multi-organ malformations in a Holstein calf. AB - A 5-day-old female Holstein calf was necropsied because of lethargy, recumbency and anorexia. At necropsy, multiple gross defects were evident in several organs, including unclosed sutures of skull bones, asymmetrical orbits, doming of the skull bones, hydrocephalus, hydranencephaly, cleft palate, brachygnathia, ventricular septal defect, mitral valve dysplasia and rudimentary lungs. On microscopic examination, pulmonary hypoplasia was characterized by reduced number of alveoli, replacement of peri-bronchiolar smooth muscles with connective tissue and small masses of undeveloped cartilage around the small airways. The present report is the first description of the congenital pulmonary hypoplasia accompanied by numerous malformations in Holstein breed. PMID- 26893817 TI - In vitro histological investigation of interactions between rat decellularized large intestine scaffold and human adipose derived mesenchymal stem cells. AB - The aim of this study was to investigate the interactions between rat intestine decellularized scaffold and human adipose derived mesenchymal stem cells. Rat large intestine was dissected in fragments and decellularized by physicochemical methods. The scaffolds were loaded by human adipose derived mesenchymal stem cells expressing green fluorescent protein. Microscopic sections were prepared from the scaffolds after two weeks of culture with stem cells and studied by histological methods. The interactions of scaffolds with MSCs were also studied by electron microscopy. Histological and electron microscopy studies revealed human mesenchymal stem cell adhesion, migration, division and maintenance during the 14 days of culture in vitro. According to the results, scaffolds prepared from rat intestine matrix could be a suitable scaffold for studying in vitro cell behaviors such as division, migration and attachment. These various behaviors of cultured cells might be due to inductive effects of the extracellular matrix derived scaffold. However, more investigations are required to discover the exact effects of this scaffold and its interactions with mesenchymal stem cells. PMID- 26893819 TI - Abnormal bisubclavian trunk arising from the aortic arch determined by cadaver dissection of a native dog: A case report. AB - Congenital anomalies of the great thoracic vessels have been reported in 20% of dogs and cats. In some cases, the vascular ring anomalies remain unrecognized throughout the lifetime of an animal. This report describes a case with an unusual vascular ring anomaly (VRA) that was detected during dissection on a cadaver of an approximately two-year-old male native mixed breed dog. No history of the animal's life was available. But, good physical condition and age of the animal based on dentition indicated the anomaly was perhaps asymptomatic. Two main branches of the aorta were identified with the initial branch being a bicarotid trunk followed by a bisubclavian trunk. The left subclavian and aberrant right subclavian arteries formed a very short trunk and arose directly from the aortic arch. No dilatation cranial to the esophageal sulcus was found. To the authors' knowledge, our case is the first report of such anomalies perhaps without any clinical signs in a native dog in Iran. PMID- 26893820 TI - No relationship between early postnatal testosterone concentrations and autistic traits in 18 to 30-month-old children. AB - BACKGROUND: Some previous research has suggested that testosterone prenatally contributes to gender differences in autistic traits, but little is known about the role of testosterone during early postnatal development (mini-puberty). Two prior studies found no sex difference in testosterone postnatally in saliva samples and detected little to no relationship between testosterone postnatally and autistic traits in toddlers. These findings may reflect late measurements of testosterone at 3 to 4 months of age, after the peak of mini-puberty at 1 to 3 months of age. The present study examined the relationship between testosterone at 1 to 3 months of age and autistic traits at 18 to 30 months of age. FINDINGS: Testosterone was measured in saliva samples collected from children at 1 to 3 months of age. When the children (40 boys, 47 girls) reached 18 to 30 months of age, parents completed the Quantitative Checklist for Autism in Toddlers (Q CHAT). Boys had higher concentrations of testosterone postnatally and higher Q CHAT scores than girls. However, testosterone did not correlate with Q-CHAT scores in boys, girls, or the entire sample. CONCLUSIONS: The current results suggest that testosterone during the early postnatal period does not contribute to later autistic traits. Given our relatively small samples and therefore limited power, however, further research could usefully examine if testosterone in saliva samples collected during the peak of mini-puberty in larger groups predicts autistic traits or other traits that show gender differences. PMID- 26893821 TI - Treatment with FTY720 has no beneficial effects on short-term outcome in an experimental model of intracerebral hemorrhage. AB - BACKGROUND: No evidence-based therapy is available for patients with acute intracerebral hemorrhage (ICH). In view of the profound inflammatory reaction in the perilesional tissue, we investigated in a well-characterized experimental model whether the administration of the immunomodulator fingolimod (FTY720) is neuroprotective in acute ICH. METHODS: ICH was induced by means of a stereotactic intrastriatal injection of collagenase type VII-S. FTY720 (1 mg/kg) was administered intraperitoneally 1 h after ICH induction. Hematoma volume was assessed spectrophotometrically at 24 h after ICH induction. The following endpoints were determined at 24 and 72 h, respectively: mortality rate and neurologic outcomes, edema formation, and MMP-9 activity. RESULTS: Twenty-four hour after ICH induction, hematoma volume was not statistically different between groups. No difference was found in mortality and neurologic outcomes at 24 and 72 h between FTY720 treated mice and controls. Edema formation was present in both groups on the ipsilateral side with no statistical difference between groups at both time points. No difference was found in MMP-9 levels after 24 and 72 h between groups. CONCLUSIONS: Our results suggest that FTY720 has no beneficial effects in the acute phase of experimental ICH. PMID- 26893823 TI - N- and O-glycan cell surface protein modifications associated with cellular senescence and human aging. AB - BACKGROUND: Glycans play essential roles in biological functions such as differentiation and cancer. Recently, glycans have been considered as biomarkers for physiological aging. However, details regarding the specific glycans involved are limited. Here, we investigated cellular senescence- and human aging-dependent glycan changes in human diploid fibroblasts derived from differently aged skin donors using a lectin microarray. RESULTS: We found that alpha2-6sialylated glycans in particular differed between elderly- and fetus-derived cells at early passage. However, both cell types exhibited sequentially decreasing alpha2 3sialylated O-glycan structures during the cellular senescence process and showed similar overall glycan profiles. CONCLUSIONS: We observed a senescence-associated decrease in sialylation and increase in galactose exposure. Therefore, glycan profiling using lectin microarrays might be useful for the characterization of biomarkers of aging. PMID- 26893824 TI - Absence of low back pain to demarcate an episode: a prospective multicentre study in primary care. AB - BACKGROUND: It has been proposed that an episode of low back pain (LBP) be defined as: "a period of pain in the lower back lasting for more than 24 h preceded and followed by a period of at least 1 month without LBP". Previous studies have tested the definition in the general population and in secondary care populations with distinctly different results. The objectives of this study (in a primary care population) were to investigate the prevalence of 1) the number of consecutive weeks free from bothersome LBP, 2) the prevalence of at least four consecutive weeks free from bothersome LBP at any time during the study period, and 3) the prevalence of at least four consecutive weeks free from bothersome LBP at any time during the study period among subgroups that reported >30 days or <=30 days of LBP the preceding year. METHOD: In this prospective multicentre study subjects with LBP (n = 262) were consecutively recruited from chiropractic primary care clinics in Sweden. The number of days with bothersome LBP was collected through weekly automated text messages. The maximum number of weeks in a row without bothersome LBP and the number of periods of at least four consecutive weeks free from bothersome LBP was counted for each individual and analysed as proportions. RESULTS: Data from 222 recruited subjects were analysed, of which 59 % reported at least one period of four consecutive weeks free from bothersome LBP. The number of consecutive pain free weeks ranged from 82 (at least one) to 31 % (9 or more). In subjects with a total duration of LBP of <= 30 days the previous year, 75 % reported a period of 4 consecutive weeks free from bothersome LBP during the study period whereas this was reported by only 48 % of subjects with a total duration of LBP of >30 days the previous year. CONCLUSION: Prevalence of four consecutive pain free weeks is found in the majority of subjects in this population logically reflects duration of LBP within the sample and may be applied on patients in primary care to demarcate a LBP episode. PMID- 26893825 TI - A survey of impulse control disorders in Parkinson's disease patients in Shanghai area and literature review. AB - BACKGROUND: Levodopa and dopamine agonists are the main treatments for Parkinson's disease (PD) in recent years. Increased drug dosages are linked to some severe side effects, one of which is impulse control disorders (ICD). Many studies have reported the related risk factors of ICDs, such as dopamine agonist, male sex, younger age, earlier age of onset and so on. This study aims to investigate the incidence of ICD in Chinese PD patients from Shanghai area, explore the association of ICD with dopamine replacement therapy (DRT). METHODS: Two hundred seventeen PD patients were consecutively recruited from the Movement Disorder Clinic of Ruijin Hospital from March to October 2013. Minnesota Impulsive Disorders Interview was used to assess the PD patients. PD patients with possible ICD would undergo a further interview by a movement disorder specialist to confirm the diagnosis. Clinical information was also collected. RESULTS: Nine PD patients (4.15 %) showed ICD behaviors as follows: hypersexuality (4, 1.84 %), pathological gambling (3, 1.38 %), binge eating (1, 0.46 %), compulsive shopping (1, 0.46 %). Compared with the non-ICD PD group, ICD PD group took more dopamine agonists (LED 119.4 +/- 86.4 mg/d vs 60.5 +/- 80.5 mg/d, P = 0.019), had higher total levodopa equivalent dosage (TLED 912.81 +/- 878.73 mg/d vs 503.78 +/- 359.14 mg/d, P = 0.031), and had higher H&Y stage (2.33 +/- 0.87 vs 1.41 +/- 0.52, p = 0.013). However, logistic regression analysis didn't reveal the above factors as independent risk factors of ICD behaviors in our study. CONCLUSION: The incidence of ICDs behaviors in PD patients in our study is much lower than in western countries. ICD-PD group took higher dopamine agonists and higher total levodopa equivalent dosage, even though logistic regression analysis didn't reveal them as independent risk factors. PMID- 26893826 TI - miR-126: A novel regulator in colon cancer. AB - Colon cancer is one of the most common, lethal diseases worldwide. Tumor metastasis and chemotherapy resistance are the main reasons for its poor prognosis and high fatality rate. Tumor development is thought of as one of the most complex cellular events as it is a multi-step cascading process involving infinite proliferation, invasion and immigration. Recently, increasing studies have demonstrated that microRNA-126 (miR-126) has an important role in colon cancer. The expression of miR-126 decreased significantly in colon cancer, particularly in highly metastatic cell lines. miR-126 controls tumor cell growth, metastasis and survival via inactivation of the oncogene signaling pathway, indicating that miR-126 may serve as a therapeutic target for anticancer therapy. Potentially, miR-126 was also reported to be an ideal molecular target as a novel biomarker for liver metastasis from colorectal cancer due to its changeable expression level. In the present review, the current knowledge regarding regulatory function of miR-126 is summarized along with its underlying mechanisms in colon cancer. PMID- 26893822 TI - Failed upregulation of TFAM protein and mitochondrial DNA in oxidatively deficient fibers of chronic obstructive pulmonary disease locomotor muscle. AB - BACKGROUND: Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD). Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms. Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls. We hypothesized that the high oxidative stress environment of COPD muscle would yield a higher presence of deletion-containing mtDNA and oxidative-deficient fibers and impaired capacity for mitochondrial biogenesis. METHODS: Vastus lateralis biopsies were analyzed from 29 COPD patients and 19 healthy age-matched controls for the presence of mtDNA deletions, levels of oxidatively damaged DNA, mtDNA copy number, and regulators of mitochondrial biogenesis as well the proportion of oxidative-deficient fibers (detected histologically as cytochrome c oxidase-deficient, succinate dehydrogenase positive (COX(-)/SDH(+) )). Additionally, mtDNA copy number and mitochondrial transcription factor A (TFAM) content were measured in laser captured COX( )SDH(+) and normal single fibers of both COPD and controls. RESULTS: Compared to controls, COPD muscle exhibited significantly higher levels of oxidatively damaged DNA (8-hydroxy-2-deoxyguanosine (8-OHdG) levels = 387 +/- 41 vs. 258 +/- 21 pg/mL) and higher prevalence of mtDNA deletions (74 vs. 15 % of subjects in each group), which was accompanied by a higher abundance of oxidative-deficient fibers (8.0 +/- 2.1 vs. 1.5 +/- 0.4 %). Interestingly, COPD patients with mtDNA deletions had higher levels of 8-OHdG (457 +/- 46 pg/mL) and longer smoking history (66.3 +/- 7.5 years) than patients without deletions (197 +/- 29 pg/mL; 38.0 +/- 7.3 years). Transcript levels of regulators of mitochondrial biogenesis and oxidative metabolism were upregulated in COPD compared to controls. However, single fiber analyses of COX(-)/SDH(+) and normal fibers exposed an impairment in mitochondrial biogenesis in COPD; in healthy controls, we detected a marked upregulation of mtDNA copy number and TFAM protein in COX(-)/SDH(+) compared to normal fibers, reflecting the expected compensatory attempt by the oxidative deficient cells to increase energy levels; in contrast, they were similar between COX(-)/SDH(+) and normal fibers in COPD patients. Taken together, these findings suggest that although the signaling factors regulating mitochondrial biogenesis are increased in COPD muscle, impairment in the translation of these signals prevents the restoration of normal oxidative capacity. CONCLUSIONS: Single fiber analyses provide the first substantive evidence that low muscle oxidative capacity in COPD cannot be explained by physical inactivity alone and is likely driven by the disease pathophysiology. PMID- 26893827 TI - Epigenetics in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, with mechanisms that remain to be elucidated. Previous studies have proposed that genes and environments are required for lupus to develop and flare. It has been found that epigenetics have a significant influence on SLE. The present review will concentrate on epigenetics in SLE. There are a number of studies reporting that autoreactive T cells and B cells in patients with SLE have evidence of altered patterns of DNA methylation, modifications of histones and microRNA (miRNA). Long noncoding RNAs (lncRNAs) are another type of noncoding RNAs, which have an important role in epigenetics. lncRNAs may possibly become a new hotspot in SLE. PMID- 26893828 TI - Pim-1 kinase as cancer drug target: An update. AB - Proviral integration site for Moloney murine leukemia virus-1 (Pim-1) is a serine/threonine kinase that regulates multiple cellular functions such as cell cycle, cell survival, drug resistance. Aberrant elevation of Pim-1 kinase is associated with numerous types of cancer. Two distinct isoforms of Pim-1 (Pim-1S and Pim-1L) show distinct cellular functions. Pim-1S predominately localizes to the nucleus and Pim-1L localizes to plasma membrane for drug resistance. Recent studies show that mitochondrial Pim-1 maintains mitochondrial integrity. Pim-1 is emerging as a cancer drug target, particularly in prostate cancer. Recently the potent new functions of Pim-1 in immunotherapy, senescence bypass, metastasis and epigenetic dynamics have been found. The aim of the present updated review is to provide brief information regarding networks of Pim-1 kinase and focus on its recent advances as a novel drug target. PMID- 26893829 TI - Analysis of the prognostic risk factors of idiopathic membranous nephropathy using a new surrogate end-point. AB - Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome (NS) in adults. The latest study of the chronic kidney disease prognosis consortium showed that a 30% decrease in the estimated glomerular filtration rate (eGFR) within 2 years could cover more patients and showed a better correlation with end-stage renal disease (ESRD), as compared with serum creatinine (SCr). The aim of the present study was to analyze prognostic factors of ESRD using a 30% decrease in eGFR within 2 years as the end-point. The medical records of patients who were diagnosed as having IMN by clinical pathology between February 2011 and August 2012 and had been followed up for >=24 months were analyzed retrospectively. A 30% decrease in eGFR or the occurrence of ESRD were the end-points. Factors affecting the prognosis were analyzed by the chi2 test and multivariate logistic regression analysis, and the cumulative risk of risk factors was analyzed by Kaplan-Meier curve. A total of 73 patients with IMN were confirmed by clinical pathology. Blood pressure, tubulointerstitial injury area (TIA), glomerular sclerosis ratio, SCr, blood urea nitrogen, cystatin C, serum albumin and 24-h urine protein. In total, 28 patients (38.4%) reached the observation end-point. Multivariate logistic regression analysis showed that only age >=60 years, serum albumin <25 g/l and TIA >25% were independent risk factors for predicting the occurrence of end-point events in the two groups (P<0.05), which increased the risk of the occurrence of end-point events in IMN patients by 3.471-, 3.195- and 6.724-fold, respectively. Kaplan-Meier curve showed that the occurrence of end-point events within 2 years was significantly higher in IMN patients whose age was >=60 years, serum albumin <25 g/l and TIA >25% (log-rank P=0.004, P=0.024 and P=0.001). The results of the present study revealed that age >=60 years, low serum albumin concentrations and severe tubulointerstitial injury are independent risk factors for the occurrence of ESRD in IMN patients. PMID- 26893831 TI - Neurological function following cerebral ischemia/reperfusion is improved by the Ruyi Zhenbao pill in a rats. AB - The present study aimed to investigate the effect and underlying mechanisms of the Ruyi Zhenbao pill on neurological function following cerebral ischemia/reperfusion in rats. Male Sprague-Dawley rats underwent middle cerebral artery occlusion following reperfusion. The rats received intragastrically either sodium carboxymethyl cellulose (control and model groups) or Ruyi Zhenbao pill at doses of 0.2, 0.4 or 0.8 g/kg. Neurological function was assessed by cylinder, adhesive and beam-walking tests after 14-day Ruyi Zhenbao pill treatment. Neurogenesis and angiogenesis were detected using immunofluorescence staining. The expression levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assays. Treatment with 0.4 and 0.8 g/kg Ruyi Zhenbao for 14 days significantly improved neurological function, and increased the number of von Willebrand Factor- and neuronal nuclear antigen-positive cells in the ischemic hemisphere of rats. Ruyi Zhenbao pill treatment also significantly enhanced the expression levels of BDNF, NGF and VEGF in the ischemic hemisphere. The results demonstrated that the Ruyi Zhenbao pill improved neurological function following ischemia in rats. The mechanisms of the Ruyi Zhenbao pill are associated with increasing the expression levels of BDNF, NGF and VEGF, and subsequently promoting neurogenesis and angiogenesis in the ischemic zone. PMID- 26893830 TI - Fas-670A>G polymorphism is not associated with an increased risk of acute myeloid leukemia development. AB - The association between the increased risk of acute myeloid leukemia (AML) and Fas promoter polymorphisms has been reported previously; however, the results are inconclusive. The present study performed one case-control study to investigate the association, and a total of 98 AML patients and 2,014 healthy controls were genotyped. The data showed that the distribution of Fas-670AA, GA and GG genotypes among the AML patients were not significantly different from those of the healthy controls, all P>0.05. Following this a sub-study was conducted to analyze individuals who neither smoked nor drank. The results demonstrated that there was still no significant association between the Fas-670 polymorphism and risk of AML development, all P>0.05. Furthermore, in order to address a more accurate estimation of the association, a meta-analysis was conducted. Data were systematically collected from the Pubmed, EMBASE and the Wanfang Library. A total of 3 studies were included in this meta-analysis, which contained 1,144 AML cases and 3,806 controls. No significant association was detected between the Fas 670A>G polymorphism and AML risk [GA+GG vs. AA: odds ratio (OR) 0.93; 95% confidence interval (CI), 0.79-1.09; GG vs. AA: OR, 1.01; 95% CI, 0.82-1.24; GA vs. AA: OR, 1.12; 95% CI, 0.94-1.32; GG vs. AA+GA: OR, 0.94; 95% CI, 0.79-1.12; G vs. A: OR, 1.01; 95% CI, 0.91-1.12; all P>0.05). The analysis clearly indicated that there was no significant connection between the Fas-670A>G polymorphism and the increased risk of AML. PMID- 26893832 TI - Expression of receptor protein tyrosine phosphatase zeta is a risk factor for triple negative breast cancer relapse. AB - Patients with triple negative breast cancer (TNBC) have a higher rate of distant recurrence and a poorer prognosis than those with other breast cancer subtypes. Therefore, it is important to study the mechanism of TNBC relapse. A retrospective immunohistochemical analysis of the expression of receptor protein tyrosine phosphatase zeta (PTPRZ1) and pleiotrophin (PTN) was performed for 325 cases of breast cancer. These samples included 66 cases of luminal A breast cancer, 67 cases of luminal B breast cancer, 78 cases of Her-2-enriched breast cancer, 78 cases of TNBC and 36 cases of relapsed TNBC (RTNBC). In addition, 30 control specimens and 30 cases of metastasized lymph nodes were examined. PTPRZ1 and PTN were highly expressed in the RTNBC group. Compared with the RTNBC group, significant differences in the expression of PTPRZ1 were observed between the TNBC, BC and control groups. A significant difference was observed in the expression of PTN in the BC group (P<0.05) compared to RTNBC, and there were no significant differences in the expression of PTPRZ1 and PTN among the molecular subtypes. No significant correlation was observed between the expression of PTPRZ1, PTN, ER, PR, Her-2 and ALN and the tumor size or menopause status. No significant correlation was identified between the expression of PTPRZ1 and PTN and the expression of CD24 and CD44. In summary, high expression of PTPRZ1 may be an independent risk indicator for TNBC recurrence and metastasis. PMID- 26893833 TI - Minocycline induces protective autophagy in vascular endothelial cells exposed to an in vitro model of ischemia/reperfusion-induced injury. AB - Minocycline has been reported to exhibit advantageous effects on ischemic stroke; however, the precise mechanism of minocycline remains to be established. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to in vitro simulated ischemia/reperfusion conditions to determine the potential effect of minocycline-induced autophagy on HUVEC damage under oxygen-glucose deprivation/reperfusion (OGD/R). The study demonstrated that minocycline enhanced autophagy in a dose-dependent manner in HUVECs exposed to OGD/R, and only low dose minocycline protected HUVECs from OGD/R-induced damage. Subsequently, 3 methyladenine (3-MA) was added into the culture media and the protective effect of minocycline was abolished. At the same time, it has been observed that simultaneous treatment with 3-MA also inhibited the autophagy activity induced by minocycline. This finding could suggest that autophagy induced by minocycline serves as one of the potential protective mechanism underlying the beneficial effects of minocycline on ischemic injury. PMID- 26893834 TI - Association of genetic variants with atrial fibrillation. AB - Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the chi2 test revealed that rs599839 (G->A) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (C->T, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minor G and T alleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals. PMID- 26893835 TI - Efficacy of alogliptin in preventing non-alcoholic fatty liver disease progression in patients with type 2 diabetes. AB - Non-alcoholic fatty liver disease (NAFLD) represents one of the most common causes of chronic liver disease worldwide and is characterized by chronic liver inflammation and fibrosis leading to cirrhosis and increased risk of liver cancer in a proportion of patients. Effective anti-fibrotic agents have yet to be approved for the treatment of NAFLD. The present study aimed to evaluate the efficacy of dipeptidyl peptidase 4 inhibitors (DPP4-I) in the prevention of NAFLD progression in NAFLD patients with type 2 diabetes. The study was a single arm, multi-centre, non-randomised study of NAFLD patients with type 2 diabetes. NAFLD was diagnosed according to ultrasonographic findings. All the patients received 25 mg/day of alogliptin for 12 months. The efficacy of alogliptin in preventing NAFLD progression was assessed using overall NAFIC scores [non-alcoholic steatohepatitis (NASH), ferritin, insulin and type IV collagen 7S] and individual component scores according to baseline haemoglobin A1c (HbA1c) levels. Of the 39 patients enrolled in the study, 16 patients (40.3%) had NAFIC scores >2 points, indicating the presence of NASH. NAFIC scores markedly decreased following 12 months of alogliptin administration, but remained >2 points in 10 patients, indicating that NASH may have persisted in these patients. The relative risks for persistent NASH were 4.92 (95% confidence interval, 0.61-40.0) in the highest HbA1c tertile group compared with those in the lowest group. However, no statistically significant linear trend was observed across all HbA1c categories (P=0.145). DPP4-I may have efficacy against NAFLD progression in patients with type 2 diabetes with relatively lower HbA1c levels. DPP4-I may represent a potential new therapeutic strategy for the prevention of disease progression in NAFLD patients with type 2 diabetes. PMID- 26893836 TI - Morphological and functional changes of the optic nerve following traumatic optic nerve injuries in rabbits. AB - The aim of the present study was to investigate the morphological changes of the optic nerve following traumatic injuries and decompression at different times after injury, and to observe the changes of the visually evoked potentials, to identify the relevant associations between surgical opportunity and the clinical effect of traumatic optic nerve injuries. Rabbits were chosen as the animal model for the study. All the rabbits were randomly divided into five groups (A-E), representing the normal control, decompression in 48 h, in 1 week, in 2 weeks and non-decompression groups, respectively. The pattern reversal visual evoked potentials (P-VEP) and morphological changes of the optic nerve were observed. The P-VEP of each healthy rabbit revealed typical NPN contours, while NPN waves in the injured rabbits were low and flat. The latent period of the P-wave was lengthened and the amplitude was reduced. The differences of the latent period and amplitude pre- and post-trauma were statistically significant. The morphological changes were also assessed. In the normal control group, the astrocytes of the optic nerve exhibited a cylindrical form and were arranged evenly on the vertical section. The neural fibers were arranged neatly, were even following application of a dye, and the cross section exhibited a normal configuration of the blood vessel. For the 48-h decompression group, the arrangement of the astrocytes was even on the vertical section, and vacuoles, slight swelling of the nerve, exudation around the blood vessel and a small amount of astrocytic hyperplasia were observed in the damaged area. In the non decompression group there were large areas of necrosis, clear nerve demyelination, serious exudation around the blood vessel and astrocytic hyperplasia were observed. In conclusion, the optic nerve decompression is beneficial to protect the visual function in indirect optic nerve injuries. Visual function may be improved by decompression in 48 h compared to 2 weeks. In order to prevent secondary axon injury and to protect visual functions, the decompression should be performed as soon as possible. PMID- 26893837 TI - Expression profiling of microRNAs in optineurin (E50K) mutant transgenic mice. AB - An E50K substitution in the transcription factor optineurin (OPTN) induces primary open-angle glaucoma (POAG). To explore the potential role of microRNAs (miRNAs) in E50K OPTN-induced POAG, miRNA expression profiling was performed on retinal samples from OPTN (E50K) transgenic and wild-type mice. The retinas were collected from 30 transgenic and 30 wild-type mice, and miRNA expression was evaluated using a genome-wide miRNA microarray. miRNAs that were differentially expressed in retinal samples from OPTN (E50K) transgenic mice were identified and validated by reverse transcription-quantitative polymerase chain reaction (RT qPCR). Additional gene ontology and signaling pathway analyses were performed using bioinformatics tools. A total of 48 miRNAs exhibited increased or decreased expression in the retinas from OPTN (E50K) transgenic mice when compared with the expression in the retinas from wild-type mice. A total of 5 miRNAs with increased expression in OPTN (E50K) transgenic mice could be grouped into one cluster as they belong to the miR-8 family and may act as regulators in the development of POAG in OPTN (E50K) transgenic mice. RT-qPCR results confirmed significantly increased expression of miR-141 in the retinas of OPTN (E50K) transgenic mice as compared to wild-type mice. In conclusion, these results show that certain miRNAs are differentially expressed in the retinas of OPTN (E50K) transgenic mice and may play roles in the pathogenesis of POAG induced by OPTN (E50K). PMID- 26893838 TI - Investigation of testosterone-mediated non-transcriptional inhibition of Ca2+ in vascular smooth muscle cells. AB - The aim of the present study was to observe the effect of short-term testosterone treatment on Ca2+ in vascular smooth muscle cells (VSMCs) of male rats. Cells were loaded with the Ca2+-sensitive fluorescent indicator Fura-2 and intracellular Ca2+ signals of VSMCs were measured using a Nikon TE2000-E live cell imaging workstation. The baseline level of cytosolic Ca2+ concentration ([Ca2+]i) in resting state VSMCs was ~100 nmol/l. Testosterone alone led to a slow increase in [Ca2+]i, but there was no significant difference compared with the ethanol vehicle control. When VSMCs were stimulated with a high-potassium solution (containing 42 mmol/l of K+), [Ca2+]i rose rapidly and remained at a high plateau level. Short-term treatment using physiological (40 nmol/l) or supraphysiological (4 umol/l) levels of testosterone at either the plateau phase or the pretreatment stage could significantly inhibit the [Ca2+]i increase induced by high-potassium solutions. Testosterone coupled to bovine serum albumin also had a similar effect and repetitive testosterone interventions over a short time-frame led to inhibition. Testosterone has a non-transcriptional inhibition effect on the [Ca2+]i of VSMCs and acts with the cell membranes of VSMCs to inhibit voltage-gated Ca2+ channel-mediated Ca2+ influx, which may be one of the mechanisms underlying testosterone-mediated vasodilation. PMID- 26893839 TI - 5-HTR2A and IL-6 polymorphisms and obstructive sleep apnea-hypopnea syndrome. AB - At present, variants of the 5-hydroxytryptamine receptor 2A (5-HTR2A) and interleukin-6 (IL-6) genes may be susceptible markers to develop for obstructive sleep apnea-hypopnea syndrome (OSAHS). Therefore, the aim of the present study was to explore the potential associations between the 5-HTR2A and IL-6 single nucleotide polymorphisms (SNPs) and OSAHS. In total there were 130 cases and 136 controls collected for genotyping of 5-HTR2A (rs6311) and IL-6 (rs1800796) SNPs. The association of these SNPs with OSAHS risk were evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) from multivariate unconditional logistic regression analyses with adjustment for gender and age. The results indicated that the genotype and allele frequencies in these two loci (rs6311 and rs1800796) were not significantly different between the cases and controls. However, carrying the 'C' allele of rs6311 has a protective effect against OSAHS via the gender-specific comparison (P=0.0409; OR, 1.744; 95% CI, 1.021-2.978). The 'G' allele and 'CG' genotype distribution of rs1800796, and 'C' allele and 'CT' genotype distribution of rs6311 have significant differences between the mild and moderate group (P<0.05). Similarly, the genotype distribution of rs6311 has differences between mild and severe cases (P=0.0026). The current research demonstrated that variants of rs6311 have an association with OSAHS in males. Additionally, polymorphisms of rs6311 and rs1800796 have relevance to the severity of OSAHS. PMID- 26893840 TI - Genotyping of clinical varicella-zoster virus isolates collected from Yunnan in Southwestern China. AB - Varicella-zoster virus (VZV) belongs to the alpha-herpesvirus family. Genetically, it is stable and is divided into several genotypes based upon the genetic variations. The genotypes of VZV are rarely studied in the Southwestern region of China. In the present study, the common genetic variations in the VZV genes were examined in 42 VZV isolates collected from the patients with herpes zoster in the Yunnan province (Southwestern China). The restriction fragment length polymorphism analysis of open reading frames (ORFs) 38, 54 and 62 in the VZV genes showed that all the collected VZV isolates were PstI, BglI and SmaI positive. The R5 variable-repeat region in these isolates was variable (R5A: 46.4%; R5B: 53.6%). The sequencing data of ORFs 1, 21, 22 and 54 indicated that 41 of the 42 collected VZV isolates could be grouped into genotype J or J1. Only one VZV isolate was identified as genotype A1 or M2. No new substitutions in the sequenced fragments were found in the collected VZV isolates. The results of the present study provided a preliminary genetic characterization of the VZV strains in the Yunnan province of Southwestern China. PMID- 26893841 TI - A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder. AB - Approximately 10-15% of intellectual disability (ID) cases are caused by genetic aberrations affecting chromosome X, a condition termed X-linked ID (XLID). Examination by whole-exome sequencing of two male siblings with microcephaly and suspected XLID with an unknown genetic basis revealed that they were both hemizygous for a predicted pathogenic variant (p.Ala897Val) causing a non synonymous substitution of an evolutionary conserved amino acid within the host cell factor C1 (HCFC1) gene. Subsequent analysis determined that this was a rare variant not identified in 100 control individuals or in online databases of control individuals. Recent studies have reported mutations affecting HCFC1 in patients with ID and dysmorphic features that are associated with defective cobalamin metabolism. Biochemical investigations did not find evidence of an association between the variant identified in the present study and cobalamin metabolic disorder. This study offers further support for mutations of HCFC1 being implicated in XLID and microcephaly, but that these are not necessarily associated with cobalamin disorder. PMID- 26893842 TI - Chemical study of the Chinese medicine Pi Han Yao. AB - The aim of the present study was to ivnestigate the chemical constituents of the Chinese medicine Pi Han Yao (Gueldenstaedtia delavayi Franch) decoction. Following this, the quantitative determination of the formononetin and maackiain content in Pi Han Yao was established. The chemical constituents were isolated by column chromatography and their structures were elucidated by analysis of spectrometric data and chemical evidence. High-performance liquid chromatography (HPLC) was used for the determination of the formononetin and maackiain content in Pi Han Yao. Seven flavanones were isolated from the Pi Han Yao decoction. Five of the chemical structures were elucidated as 1, 7,2'-dihydroxy-4'-methoxy isoflavanol; 2, maackiain; 3, formononetin-7-O-beta-D-glucoside; 4, formononetin; and 5, 9-(beta-D-ribofuranosyl)-adenosine. The other two compounds and their structures require further study. Additionally, the linear range of formononetin and maackiain were 0.03992-0.3992 and 0.0292-0.292 ug, and their recoveries were 100.31 and 100.44%. To the best of our knowledge, compounds 1-5 were obtained from Pi Han Yao for the first time. The HPLC method use for determination of formononetin and maackiain in Pi Han Yao was simple, accurate and reliable. Findings from the present study suggest that these methods may be used to evaluate the quality of Pi Han Yao and provide an experience basis for quality standards of this medicinal material. PMID- 26893843 TI - Silencing of FRAT1 by siRNA inhibits the proliferation of SGC7901 human gastric adenocarcinoma cells. AB - Frequently rearranged in advanced T cell lymphomas-1 (FRAT1) positively regulates the Wnt/beta-catenin signaling pathway by inhibiting glycogen synthase kinase-3 mediated phosphorylation of beta-catenin. FRAT1 is a proto-oncogene, implicated in tumorigenesis. The present study aimed to investigate the effects of FRAT1 silencing on the proliferation and apoptosis of SGC7901 cells. FRAT1 in SGC7901 cells was silenced by RNA interference. Reverse transcription-quantitative polymerase chain reaction was used for the analysis of FRAT1 mRNA and western blotting was used to evaluate FRAT1 and beta-catenin protein levels. Cell proliferation was analyzed by the MTT assay. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The expression of FRAT1 mRNA, FRAT1 and beta-catenin protein in FRAT1-silenced SGC7901 cells were reduced significantly compared to untreated cells. The proliferation of FRAT1 silenced SGC7901 cells decreased significantly The FRAT1 silenced SGC7901 cells were arrested at G0/G1 stage to a greater degree, and apoptosis was increased. In summary, silencing of FRAT1 inhibits SGC7901 cell proliferation and induces apoptosis, possible through a reduction in beta-catenin expression. FRAT1 may serve as a prognostic biomarker and therapeutic target for gastric cancer. PMID- 26893844 TI - Association of the interleukin-18 receptor 1 and interleukin-18 receptor accessory protein polymorphisms with the risk of esophageal cancer. AB - Esophageal cancer is the fourth leading cause of cancer-associated fatalities and the fourth most commonly diagnosed cancer. In addition to environmental risk factors, genetic factors may have a significant role in esophageal cancer carcinogenesis. A hospital-based case-control study was conducted to evaluate the genetic effects of functional single-nucleotide polymorphisms in the interleukin 18 (IL-18), IL-18 receptor 1 protein (IL-18R1), IL-18 receptor accessory protein (IL-18RAP) and IL-28B on the development of esophageal cancer. In total, 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for the present study. The IL-18 rs360719 A>G, IL-18R1 rs13015714 G>T, IL-18RAP rs917997 C>T and IL-28B rs8099917 T>G genotypes were determined. No association was observed between the IL-18R1 rs13015714 G>T, IL-18RAP rs917997 C>T and IL-28B rs8099917 T>G polymorphisms and the risk of ESCC. However, in stratification analyses, a significantly decreased risk of ESCC associated with the IL-18R1 rs13015714 G>T polymorphism and a significantly increased risk of ESCC associated with the IL-18RAP rs917997 C>T polymorphism was evident among male patients and patients who smoked or consumed alcohol. These findings highlighted that functional polymorphisms IL-18R1 rs13015714 G>T and IL-18RAP rs917997 C>T may contribute to ESCC susceptibility among these subgroups. However, the present results were obtained with a limited sample size and further epidemiological studies are warranted to clarify the role of IL-18R1 and IL-18RAP variants in the development of ESCC. PMID- 26893845 TI - Analysis of XRCC2 and XRCC3 gene polymorphisms in pancreatic cancer. AB - The double-strand break DNA repair pathway, including XRCC2 and XRCC3 genes, is implicated in maintaining genomic stability and therefore could affect the pancreatic cancer risk. The aim of the present study was to evaluate the clinical significance of the XRCC2 and XRCC3 gene polymorphisms in patients with pancreatic cancer. The present study included 203 patients: 101 with pancreatic cancer and 102 healthy controls. The Arg188His XRCC2 and the Thr241Met XRCC3 gene polymorphisms have been studied in DNA isolated from blood samples. The associations of the analysed genotypes and clinical data at diagnosis have been evaluated. The frequencies of the genotypes of the Arg188His XRCC2 and Thr241Met XRCC3 polymorphisms did not differ significantly between patients and controls. The study did not identify a correlation between the XRCC2 and XRCC3 genes polymorphisms and tumor size or localisation. Analysed polymorphisms were also not associated with the gender and age of the patient, or the presence of regional or distant metastases. In conclusion, the present study did not suggest an association between the Arg188His XRCC2 and the Thr241Met XRCC3 polymorphisms and the clinical data of patients with pancreatic cancer. PMID- 26893846 TI - Association between MMP-2 expression and prostate cancer: A meta-analysis. AB - Matrix metalloproteinase-2 (MMP-2) is a member of the MMP family, which is associated with numerous types of cancer. Although it has been widely reported, the prognostic value of MMP-2 expression in prostate cancer (PCa) remains controversial. Thus, the present meta-analysis was conducted to investigate the association and prognostic value of MMP-2 expression in PCa. PubMed, Cochrane Library and the China National Knowledge Infrastructure databases were searched for all the published case-control studies on the association between MMP-2 expression and PCa until July 2015. The odd ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the association of MMP-2 expression and PCa. ORs and 95% CIs were applied to clarify this association. Several subgroup analyses were also conducted according to different indexes in the case group. In total, 8 studies including 675 patients were included in the final meta-analysis. The results of the meta-analysis showed that MMP-2 expression in the PCa group was significantly higher than that in the benign prostatic hyperplasia (BPH) group (95% CI, 0.06-0.15; Z=10.48; P<0.00001). Furthermore, MMP-2 expression was significantly associated with Gleason Score (95% CI, 0.18-0.68; Z=3.09; P=0.002) and clinical stages (95% CI, 0.12-0.82; Z=2.36; P=0.02), and not significantly associated with Gleason score serum prostate specific antigen (95% CI, 0.30-1.66; Z=0.80; P=0.43). In conclusion, MMP-2 is overexpressed in PCa tissues compared with BPH. The expression of MMP-2 was significantly associated with the grade of PCa malignancy. PMID- 26893847 TI - Associations of platelet-activating factor acetylhydrolase gene polymorphisms with risk of ischemic stroke. AB - Platelet-activating factor acetylhydrolase (PAF-AH) has an important function in the pathogenesis of ischemic stroke. The aim of the present study was to investigate the correlation between the variation of polymorphisms (R92H and V279F) in PAF-AH and ischemic stroke. A total of 375 patients with ischemic stroke and 370 healthy controls were recruited into the study. Polymorphisms of V279F and R92H in PAF-AH were detected by polymerase chain reaction and DNA direct sequencing method. No significant association was observed between V279F and ischemic stroke. However, the RH+HH genotype, RH genotype and H allele of R92H were significantly associated with an increased risk of ischemic stroke (P=0.02, P=0.03 and P=0.02, respectively), In addition, these correlations remained following adjustment for confounding risk factors of stroke. Furthermore, subgroup analysis showed that a significant association with R92H was identified in the large-artery atherosclerotic stroke subgroup. These findings indicated that variation of R92H in the PAF-AH gene may contribute to ischemic stroke susceptibility in the population studied. PMID- 26893849 TI - Development of combined thymic carcinoma and thymoma in an extrathymic lesion during long follow-up for recurrent thymoma. AB - The present study reported a rare case of combined thymic squamous cell carcinoma and thymoma exhibiting a mass on the left chest wall. The patient underwent thoracotomy for invasive thymoma 15 years previously, however, suffered a relapse in the left intrathoracic space. Radiotherapy, chemotherapy and partial resection, as secondary surgery for the intrathoracic mass, were performed. The histological findings in the resected specimens revealed type B3 thymoma. As the patient developed a left chest wall mass and pain in 2013, the mass was resected. The histological findings indicated two separate components composed of type B3 thymoma and squamous cell carcinoma. Immunohistological findings revealed that the thymoma cells were positive for CD5, while the thymic carcinoma cells were negative for CD5. Several reports have demonstrated the coexistence of thymic carcinoma and thymoma in the primary thymus, however, the development of a combined tumor in an extrathymic lesion is extremely rare. The present case had a long follow-up for recurrent thymoma. The present case indicated that the development and/or coexistence of malignant components in the thymoma must be taken into consideration for the treatment and/or management of patients with thymoma and that a pre-existence of CD5 expression in thymoma and the lost change may be associated with the process of malignant transformation. PMID- 26893848 TI - Metabolism of arachidonic acid by the cytochrome P450 enzyme in patients with chronic Keshan disease and dilated cardiomyopathy. AB - Keshan disease (KD) is an endemic cardiomyopathy. The etiology of KD is selenium deficiency; however, it is not the only one and there is no effective approach to preventing and curing this disease. The aim of the present study was to explore the differences in the role of arachidonic acid (AA) by the cytochrome P450 enzyme between chronic KD (CKD), dilated cardiomyopathy (DCM) and control patients. Reverse transcription-quantitative polymerase chain reaction was used to detect the CYP1A1 and CYP2C19 gene expression levels in 6 CKD patients, 6 DCM and 6 healthy controls. An enzyme-linked immunosorbent assay kit was applied to detect serum protein expression of CYP1A1 and CYP2C19, AA and epoxyeicosatrienoic acids (EETs), and 20-hydroxyeicosatetraenoic acids (20-HETE) in 67 CKD patients, 28 DCM, and 58 controls. The present results showed that the expression levels of CYP1A1 and CYP2C19 genes were significantly upregulated compared with the control group (P<0.01). The expression level of the CYP1A1 protein in the CKD (49.55+/ 35.11 pg/ml) and DCM (46.68 +/-13.01 pg/ml) groups were enhanced compared with the control group (44.33+/-16.76 pg/ml) (P<0.01). The production of the CYP2C19 protein in the CKD (57.52+/-28.22 pg/ml) and DCM (56.36+/-11.26 pg/ml) groups was enhanced compared with the control group (51.43+/-10.76 pg/ml). The concentrations of AA in the CKD (126.27+/-47.91 ng/ml) and DCM (133.24+/-58.67 ng/ml) groups were also significantly increased compared to the control (78.16+/ 23.90 ng/ml) (P<0.001). The concentration of 20-HETE in the CKD (198.34+/-17.22 ng/ml) and DCM (194.46+/-20.35 ng/ml) groups were also significantly increased compared to the control (130.10+/-16.10 ng/ml) (P<0.001). The only difference between CKD and DCM was for the expression of the CYP1A1 gene and protein. The maximum concentration of EETs was in the control group (44.37+/-6.14 pg/ml), and the other two groups were lower than the control group (P<0.001). These findings indicated that AA-derived CYP450 metabolites may have a critical role in the pathogenesis of KD and DCM. Upregulation of the CYP2C19 gene and frequent protein expression may be a protective compensation reaction, while CYP1A1 may aggravate myocardial injury. PMID- 26893850 TI - Clinical characteristics and pathology of thyroid-like follicular carcinoma of the kidney: Report of 3 cases and a literature review. AB - Thyroid-like follicular carcinoma (TLFC) of the kidney is an extremely rare type of renal tumor, which has not been classified under a known subtype of renal cell carcinoma. It is histologically similar to the primary thyroid follicular carcinoma; however, the characteristics lack thyroid immunohistochemical markers. The aim of the present study was to illustrate the clinical characteristics of 3 new cases along with a review of the literature. The patients were compared with regards to gender, age, location and size of the tumor, imageology, morphology, immunohistochemistry and prognosis. According to the limited data, TLFC occurs mainly in young women and its clinical manifestations have no difference with other renal tumors. Its imageological features resemble a large spectrum of benign and malignant renal and extra-renal conditions, which should be eliminated in the diagnostic process. Confirmed diagnosis depends on the examination of pathology and immunohistochemistry. Surgical ablation is the preferred therapeutic method. Currently, TLFC has a relatively good prognosis; however, this conclusion requires further cases and long-term follow-ups. Improving the understanding of TLFC can help avoid misdiagnosis and prevent inappropriate treatment. PMID- 26893851 TI - Mogamulizumab treatment of refractory peripheral T-cell lymphoma following autologous stem cell transplantation: A case report. AB - Peripheral T-cell lymphoma (PTCL) represents a small heterogeneous group of non Hodgkin lymphoma (NHL) that accounts for ~10% of NHLs in western countries and ~25% of NHLs in Japan. The disease remains extremely difficult to treat. Therefore, novel treatment modalities are required. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody that targets CC chemokine receptor 4. To the best of our knowledge, the efficacy of mogamulizumab in patients who are refractory to conventional chemotherapy following autologous stem cell transplantation has not been investigated previously. The present study reports a patient with PTCL who relapsed following autologous stem cell transplantation and became resistant to salvage chemotherapy, in whom mogamulizumab showed evident efficacy without severe adverse event. PMID- 26893853 TI - High expression of HEF1 predicts a poorer prognosis of hepatocellular carcinoma: A retrospective study. AB - Human enhancer of filamentation 1 (HEF1), a scaffold protein, is highly expressed in a variety of cancer types and is involved cancer cell growth, migration and invasion. The prognostic value of HEF1 in hepatocellular carcinoma (HCC) remains to be elucidated. The aim of the present study was to assess the association between the expression of HEF1, the clinical/pathological parameters and survival in HCC. In the present study, immunohistochemistry was performed to investigate the protein expression of HEF1 in 123 hepatocellular carcinoma tissues and their adjacent normal liver tissues. Spearman's rank correlation, Kaplan-Meier plots and Cox regression model were used to analyze the data. Overexpression of HEF1 protein was observed in HCC tissue when compared with their adjacent non malignant liver tissue. High expression of HEF1 correlated with higher advanced tumor, node, metastasis (TNM) stage and vascular invasion (P<0.05). In univariate and multivariate analysis, the expression of HEF1 was identified as an independent prognostic factor in the 123 patients with HCC. In subgroup analysis, high expression of HEF1 correlated with a poorer prognosis in advanced (TNM III+IV) stages (P<0.05). These findings demonstrated the potential value of detecting the expression of HEF1 by immunohistochemistry as a prognostic biomarker and therapeutic target for patients with HCC. PMID- 26893852 TI - Valganciclovir and bevacizumab for recurrent glioblastoma: A single-institution experience. AB - Prolonged treatment with adjuvant valganciclovir has been shown in one retrospective study to exert a significant effect on overall survival (OS) in newly diagnosed patients with glioblastoma multiforme (GBM). However, studies evaluating the effectiveness of valganciclovir in the treatment of recurrent GBM have not been performed. We evaluated the effect of valganciclovir in the recurrent setting in combination with bevacizumab therapy. A retrospective analysis was performed on patients treated for recurrent GBM with off-label valganciclovir and bevacizumab at Vanderbilt University. We identified 13 patients who received valganciclovir plus bevacizumab at some point during their treatment, 8 of whom were started on valganciclovir and bevacizumab concurrently upon first recurrence, whereas 5 had valganciclovir added to their bevacizumab regimen prior to a second recurrence. of these patients, 12 were pathologically confirmed to have GBM, and 1 patient was diagnosed with gliosarcoma. We also identified an institutional cohort of 50 patients who had not been exposed to valganciclovir, but were treated with bevacizumab for first recurrence. The progression-free survival (PFS) at 6 months (PF6) and median OS (mOS) in the valganciclovir plus bevacizumab group was 62% and 13.1 months, respectively, for all 13 patients, and 50% and 11.3 months, respectively, for the 8 concurrently treated patients. In the institutional bevacizumab cohort, the PF6 and mOS were 34% and 8.7 months, respectively. In this retrospective analysis, valganciclovir in combination with bevacizumab exhibited a trend toward improved survival in patients with recurrent GBM. However, given the small sample size and the retrospective nature of this study, a larger prospective study is required to confirm these results. PMID- 26893855 TI - One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis. AB - The one-step nucleic acid amplification (OSNA) assay is used to semiquantitatively measure the cytokeratin (CK)19 mRNA copy numbers of each sentinel lymph node (SLN) in breast cancer patients. The aim of the present study was to evaluate whether the diagnosis of >=4 LN metastases is possible using the OSNA assay intraoperatively. Between May, 2010 and December, 2014, a total of 134 patients who underwent axillary lymph node dissection (ALND) of positive SLNs were analyzed. The total tumor load (TTL) was defined as the total CK19 mRNA copies of all positive SLNs. The correlation between TTL and >=4 LN metastases was evaluated. Of the 134 patients, 31 (23.1%) had >=4 LN metastases. TTL >=5.4*104 copies/ul evaluated by receiver operator characteristic curve analysis was examined along with other clinicopathological variables. In the multivariate analysis, only TTL >=5.4*104 copies/ul was correlated with >=4 LN metastases (odds ratio = 2.95, 95% confidence interval: 1.17-7.97, P=0.022). Therefore, TTL assessed by the OSNA assay has the potential to be a predictor of >=4 LN metastases and it may be useful for the selection of patients with positive SLNs in whom ALND may be safely omitted. PMID- 26893854 TI - Immunohistochemical expression levels of p53 and eIF4E markers in histologically negative surgical margins, and their association with the clinical outcome of patients with head and neck squamous cell carcinoma. AB - Molecular markers can be used to identify residual cancer at the surgical margins of head and neck squamous cell carcinoma (HNSCC) and assist in evaluating the complete resection of the tumour. The purpose of the present study was to investigate the expression levels of prognostic molecular markers at the histological tumour free surgical margins. In the present clinical retrospective study, 24/48 patients were selected with negative surgical margins for further analysis with immunohistochemical staining. Contingency tables and Fisher's exact tests were used to investigate the association between the expression levels of p53 and eukaryotic translation imitation factor 4E (eIF4E) with the clinical outcomes for patients with HNSCC. The expression levels of p53 and eIF4E were 54.2 and 87.5%, respectively, in the surgical margins of patients with HNSCC. A total of 3/7 patients with recurrent cancer (42.8%) were identified with p53 positive margins, and 6 (85.7%) patients exhibited recurrence with eIF4e-positive margins. No statistically significant differences were identified for the recurrence risk between the overexpression of p53 and eIF4E in the surgical margins (P=0.88 and P=0.99, respectively). The eIF4E marker appears to be a more marked prognosticator compared with p53, as overexpression of eIF4E was identified in the margins of 6/7 patients with local recurrence. PMID- 26893856 TI - Intravenous low-grade endometrial stromal sarcoma with intracardiac extension: A CASE OF inaccurate tumor location on contrast-enhanced computed tomography. AB - We herein report a case of low-grade endometrial stromal sarcoma with intracardiac extension in a 58-year-old woman with a uterine tumor with intravascular involvement. The tumor was suspected preoperatively to be an endometrial stromal sarcoma by magnetic resonance imaging. The extent of intravascular involvement was determined to be below the level of the renal veins on preoperative contrast-enhanced computed tomography (CT). However, perioperative echography revealed that the tumor extended to the right atrium. An emergency cardiotomy with extracorporeal circulation was required. The risk of tumor embolism was reduced through transection of the inferior vena cava, but the tumor was difficult to remove completely. Postoperative hormonal therapy reduced the size of the residual tumor and no recurrence was detected for 1 year. The preoperative contrast-enhanced CT was unable to detect the free-floating intravascular tumor. This case illustrates a limitation of CT and indicates that accurate determination of the tumor extent for planning a surgical strategy in similar cases should be performed using multiple imaging methods. PMID- 26893858 TI - Primary intraosseous squamous cell carcinoma in pre-existing keratocystic odontogenic tumor: A case report and literature review. AB - Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare type of odontogenic carcinoma that arises within the jaws. PIOSCC has no initial connection with oral mucosa and possibly develops from the residues of the odontogenic epithelium or from an odontogenic cyst or tumor. The diagnosis of PIOSCC can be difficult as it must be differentiated from other odontogenic carcinomas, such as malignant ameloblastoma, from SCCs arising from the overlying oral mucosa, from the primary tumors of the maxillary sinus or nasal mucosa, and from the tumors that have metastasized to the jaws from other primary sites. The present study reported a rare case of a 59-year-old male patient with a course of keratocystic odontogenic tumor for 25 years, between 1988 and 2013, which eventually transformed into PIOSCC after at least five recurrences and corresponding treatments. The mandible excision and titanium plate reconstruction was performed. Follow-up examinations have revealed no sign of recurrence thus far. The present study discussed this case from three aspects of clinical history, radiological examination and pathological features. PMID- 26893857 TI - Evaluation of in vivo efficacy of radiofrequency ablation with D-sorbitol in animal liver. AB - Percutaneous radiofrequency ablation (RFA) enables cauterization of liver cancer in a limited number of sessions without major complications. In contrast to the efficacy of this technique, the size of coagulation necrosis is limited due to increased impedance. D-sorbitol has been used as an irrigating fluid during transurethral resection of the prostate, since it is considered to be a dielectric fluid. In order to determine whether D-sorbitol enhances the effect of RFA, RFA was performed by slowly injecting 3% D-sorbitol near the tip of the RFA needle. The maximum of the total injected volume of D-sorbitol was 20 ml and RFA was terminated if the threshold of impedance was exceeded. RFA and D-sorbitol RFA were performed in 5 different parts of pig livers and dog livers in vivo. The total volumes of coagulation necrosis in the D-sorbitol RFA group were significantly higher compared with those in the RFA group. The total delivered energy in the D-sorbitol RFA group was also higher compared with that in the RFA group, due to the suppression of impedance elevation. No significant complications, such as bleeding or damage, were observed during the D-sorbitol RFA procedure in the in vivo model. In conclusion, RFA combined with D-sorbitol increases the total volume of coagulation necrosis through controlling impedance in the ablated liver and, therefore, D-sorbitol may be useful for the treatment of liver cancers. PMID- 26893859 TI - Denosumab-associated osteonecrosis of the jaw affects osteoclast formation and differentiation: Pathological features of two cases. AB - Medication-related osteonecrosis of the jaw (ONJ) is caused by antiresorptive (bisphosphonates and denosumab) and antiangiogenic agents, with the first report of denosumab-related ONJ emerging in 2010. To date, although certain case reports on denosumab-related ONJ have been published, those of ONJ caused by a single application of the drug are scarce. In addition, only one report described the histopathological features of this condition, although not completely; only the sequestrum resected by conservative surgery was evaluated. Although conservative treatment is recommended, the effectiveness of extensive surgery in the early stages of bisphosphonate-related ONJ has been described in recent years. Here we report the clinical and histopathological features of denosumab-related ONJ caused by single application of the drug, which was treated by extensive surgery in two patients. Histopathological analysis revealed a decreased number of osteoclasts in viable bone around the sequestrum, and these appeared morphologically immature, as indicated by the presence of very few nuclei. These findings are different from those for bisphosphonate-related ONJ and may assist in elucidating the mechanism underlying denosumab-related ONJ. Furthermore, extensive surgery may be effective for the management of this condition. PMID- 26893860 TI - Genetic alterations in lung adenocarcinoma with a micropapillary component. AB - Pulmonary adenocarcinoma (PA) with a micropapillary component (PA-MPC) is known as an aggressive subtype of PA. The molecular profiles of PA-MPC have not been well characterized. the pathological reports of patients who underwent surgical resection for lung cancer between April, 2004 and May, 2012 were reviewed. Of the 674 patients diagnosed with PA, 28 were found to have MPC. A total of 138 resected PAs without MPC were selected in the same period to serve as age-, gender- and smoking status-matched controls to the PA-MPC group. Mutational status was determined by the following two methods: SNaPshot assay based on multiplex polymerase chain reaction (PCR), primer extension and capillary electrophoresis that was designed to assess 38 somatic mutations in 8 genes [AKT1, BRAF, endothelial growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), mitogen-activated protein kinase kinase 1, neuroblastoma RAS viral oncogene homolog, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and phosphatase and tensin homolog]; and a PCR based sizing assay that assesses EGFR exon 19 (deletions), EGFR exon 20 (insertions) and human epidermal growth factor receptor 2 exon 20 (insertions). echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (EML4-ALK) was screened by ALK immunohistochemistry and confirmed using the reverse transcription PCR assay and the break-apart fluorescence in situ hybridization assay. Regarding genetic alterations, 13 (46.4%) of the 28 PA MPCs harbored mutually exclusive mutations: 9 (32.1%) EGFR mutations, 1 (3.6%) KRAS mutation and 3 (10.7%) EML4-ALK fusion genes. PAs without MPC harbored 42 (30.4%) EGFR mutations, 17 (12.3%) KRAS mutations, 3 (2.2%) EML4-ALK fusion genes and 1 (0.7%) PIK3CA mutation. EML4-ALK fusion genes appeared to occur significantly more frequently in PA-MPCs compared with PAs without MPC (P=0.027). Although the sample size was small, our study suggests that the molecular pathogenesis of PA-MPC may be different from that of other adenocarcinomas. PMID- 26893861 TI - Occurrence of an intrathoracic desmoid tumor following breast cancer treatment: A case report. AB - Desmoid tumors are rarely observed tumors that develop from deep muscle and aponeurotic tissues. They are histologically intermediate, and exhibit a local aggressive course. These tumors have been observed in the abdominal region, and are rarely encountered in the thoracic wall. The most effective treatment appears to be surgery. A 59-year-old female patient was admitted with the complaint of right breast pain and a palpable mass. The patient had undergone a modified radical mastectomy surgical procedure of the right breast due to invasive breast carcinoma 10 years before. A mass with a soft tissue density and a size of 44*22 mm was detected in the thoracic computed tomography of the patient, which subsequently resulted in biopsy followed by surgery. As a result of the pathological examination of the mass, the diagnosis was determined as desmoid tumor. Due to the closeness of the tumor to the surgical margin, the patient was administered radiotherapy and maintenance imatinib treatment was started. PMID- 26893862 TI - Adenocarcinoma of the lung with concomitant ALK fusion gene and EGFR gene mutation: A case report and literature review. AB - Targeted therapy is currently a very popular approach to cancer treatment. Personalized targeted therapy of non-small-cell lung cancer (NSCLC) is based on the mutation status of epithelial growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog, B-Raf proto-oncogene and anaplastic lymphoma kinase (ALK) fusion gene, with different mutations requiring different treatment. Herein, we present a rare case of adenocarcinoma of the lung harboring EGFR- and ALK-activating mutations simultaneously. The patient is currently on pemetrexed and carboplatin chemotherapy and faring well; follow-up will be continued. It is recommended that the biological behavior of cancers with coexisting genetic mutations and their clinicopathological characteristics are more closely investigated in future studies, in order to determine the sensitivity of such cancers to targeted drugs and select the optimal agent. PMID- 26893863 TI - A rare case of oligoastrocytoma with atypical symptoms initially diagnosed as multiple sclerosis: A case report. AB - Oligoastrocytoma (OA) is an extremely rare tumor that may be difficult to diagnose, as it mimics multiple sclerosis (MS) clinically and radiologically. OA and MS are both space-occupying lesions. The symptoms of OA are complex and depend on tumor location and size. The clinical symptoms of OA are frequently not typical of glioma; therefore, OA is associated with a high misdiagnosis rate. We herein share our experience with diagnosing a rare OA case with atypical symptoms, which was initially diagnosed as MS, while stereotactic biopsy provided the final diagnosis. Due to the rarity and high misdiagnosis rate of OAs, it is suggested that clinical physicians update their knowledge regarding brain tumor classification and increase their awareness of rare tumor occurrence. PMID- 26893864 TI - Primary peripheral nerve sheath tumors of the thyroid gland: A case report and literature review. AB - Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are rare, with fewer than 30 cases reported in the medical literature to date. Primary PNSTs of the thyroid gland are classified into malignant and benign PNSTs. The benign PNSTs may be further subclassified into neurofibromas and Schwannomas. This is the case report of a 51-year-old male patient presenting with multiple primary PNSTs involving the left lobe of the thyroid gland. The patient underwent total excision of the thyroid gland and the pathological results indicated a Schwannoma with Antoni type A and B cells. The literature was reviewed briefly and, to the best of our knowledge, this is the first case report of multiple primary PNSTs of the thyroid gland. PMID- 26893865 TI - Lessons from the past: Long-term safety and survival outcomes of a prematurely terminated randomized controlled trial on prophylactic vs. hemoglobin-based administration of erythropoiesis-stimulating agents in patients with chemotherapy induced anemia. AB - Prophylactic erythropoiesis-stimulating agent (ESA) administration for chemotherapy-induced anemia (CIA) is not supported by current guidelines. Long term follow-up of patients WHO had been treated with ESA for CIA in the past may provide useful information. In 2002, we undertook a prospective, randomized phase III trial of prophylactic vs. hemoglobin (Hb)-based (threshold: 11 mg/dl) ESA administration in patients with solid tumors and CIA. ESA administration FOR CIA was permanently suspended in 2007 in view of published data at that time, while patient surveillance continued. Among 630 evaluable patients, 38.6% were male, 50.9% had advanced cancer at diagnosis, 40.6% had Hb levels <12 mg/dl at baseline and 47.9% received ESA prophylactically (1:1 randomization). The major tumor types included colorectal (36.0%), breast (20.6%), non-prostate genitourinary (11.0%) and lung CANCER (8.4%). After a median follow-up of 85.4 months, 358 patients had relapsed and 380 had succumbed to the disease. Patients in the prophylactic ESA group (GROUP A; experimental arm), as compared with those in the Hb-based group (GROUP B; iron supplementation alone), exhibited A significantly more prominent increase in median Hb levels, particularly in the subset of patients with non-metastatic disease (two-sided P<0.01) among patients receiving chemotherapy for advanced cancer, those who received ESAs prophylactically exhibited a lower incidence of CIA (all grades: P=0.014, grades 3-4: P=0.034) and fatigue (all grades: P<0.001, grades 3-4: P=0.055), but a higher rate of a composite outcome encompassing all thrombosis-related events (all grades: P=0.043, grades 3-4: P=0.099). These differences were less prominent in the group of patients who received adjuvant treatment. There were no significant differences in overall mortality and relapse/progression rates between the two groups. therefore, prophylactic, compared with Hb-based, administration of ESAs for CIA in patients with solid tumors, was found to be associated with a significantly lower incidence of anemia and fatigue, but with a marginally higher rate of thrombosis-related adverse events, particularly in patients receiving first-line chemotherapy for advanced cancer. PMID- 26893866 TI - Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis. AB - p53 and glutathione S-transferase M1 (GSTM1) are the most popular suppressor genes. Several previous studies demonstrated positive associations of these gene polymorphisms with numerous cancer types, including hepatocellular cancer, while the association between p53/GSTM1 polymorphisms and the nasopharyngeal carcinoma (NPC) risk was inconsistent and underpowered. However, no studies investigating the combinational effect of these two genes on NPC risk were performed. To confirm the effects of p53 and GSTM1 polymorphisms on the risk of NPC, a meta analysis of all the available previous studies associating p53 and GSTM1 with the risk of NPC was performed. A comprehensive search of PubMed, Web of Science and SD database until November 2014 was performed to identify the relevant studies. The data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, five studies with 1,419 cases and 1,707 controls were included for the p53 polymorphism and three studies with 837 cases and 1,299 controls were included for the GSTM1 polymorphism. Regarding p53, a significantly increased NPC risk was observed in the overall population (C vs. G, OR, 1.245; 95% CI, 1.045-1.483; P=0.014; additive models: CC vs. GG, OR, 1.579; 95% CI, 1.100-2.265; P=0.013 and CG vs. GG, OR, 1.230; 95% CI, 1.039-1.456; P=0.016; dominant model, OR, 1.321; 95% CI, 1.127-1.549; P=0.001; recessive model, OR, 1.429; 95% CI, 1.017-2.009; P=0.040). Concerning GSTM1, a significantly increased NPC risk was observed in the overall population (null versus non-null, OR, 1.282; 95% CI, 1.075-1.530; P=0.006). In the subgroup analyses stratified by the source of controls, a significant association of p53 with NPC risk was also demonstrated, while no association with GSTM1 was observed. Therefore, the p53 G72C polymorphism may have a susceptible role in the carcinogenesis of NPC, while genetic deletion of GSTM1 may contribute to increased susceptibility to NPC. Further large and well designed studies are required to confirm this association. PMID- 26893867 TI - Preoperative mean corpuscular hemoglobin affecting long-term outcomes of hepatectomized patients with hepatocellular carcinoma. AB - Pretreatment anemia has been reported to be associated with survival in several solid tumor types. In terms of survival, only limited data on the hemoglobin (HGB) level in hepatocellular carcinoma (HCC) have been published and no data on mean corpuscular hemoglobin (MCH) level in HCC is available. The present study sought to examine the role of HGB and MCH levels in predicting long-term survival of patients with HCC who undergo resection. A retrospective study of 399 consecutive patients (1987-1994) who underwent hepatic resection for HCC in Sun Yat-Sen University Cancer Centre was performed. Serum HGB and MCH levels were examined preoperatively, and their prognostic capabilities were evaluated by Cox's proportional hazard model. Among the whole cohort, the HGB level appeared to be positively correlated with the MCH level (P<0.001). Survival analysis revealed that low levels of HGB (P=0.007) and MCH (P<0.001) were correlated with shorter overall survival (OS). Multivariate analysis revealed that MCH level was independently associated with OS (P<0.001), however, not HGB (P=0.278). In addition, 129 patients with large HCC (>=10 cm) tended to have a poorer OS (P<0.001) when compared with patients with smaller HCC. On subanalysis of patients with large HCC, MCH level also retained its stratified significance (P=0.001). Along with common clinicopathological variables, these results suggested that MCH, however, not HGB, may be useful in assessing prognosis for patients with HCC who undergo hepatectomy, particularly in identifying patients with large HCC who are most likely benefit from resection. PMID- 26893868 TI - Circulating microRNA-21 as a potential diagnostic marker for colorectal cancer: A meta-analysis. AB - MicroRNA-21 (miR-21) is overexpressed in the serum of patients with colorectal cancer (CRC), suggesting that miR-21 is a promising diagnostic biomarker for CRC. Therefore, a meta-analysis was performed to assess the diagnostic value of serum miR-21 in CRC patients. This meta-analysis included 9 studies with 746 CRC patients and 476 healthy controls. Two independent researchers identified and extracted study characteristics from eligible studies that were searched from literature databases. The quality of the eligible studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies. Bivariate and hierarchical summary receiver operating characteristic models were used in the meta-analysis. The pooled sensitivity and specificity were 72% [95% confidence interval (CI), 62-80] and 85% (95% CI, 80-88), respectively. The pooled positive- and negative-likelihood ratios were 4.65 (95% CI, 3.42-6.33) and 0.33 (95% CI, 0.24-0.47), respectively. The diagnostic odds ratio value was 14.03 (95% CI, 7.65-25.74), and the area under the summary receiver operator characteristic curve was 0.87. The present results indicated that miR-21 has a potential diagnostic value with moderate sensitivity and good specificity for CRC. Further prospective studies must be conducted to evaluate the diagnostic accuracy of miR-21. PMID- 26893869 TI - Curative effect of bevacizumab combined with chemotherapy in advanced or recurrent uterine sarcoma. AB - The aim of this study was to investigate the clinical effect of bevacizumab (BEV) combined with chemotherapy in advanced or recurrent uterine sarcoma. The clinical data of 4 patients with advanced or recurrenct uterine sarcoma, who received treatment with BEV combined with chemotherapy in our hospital between May, 2006 and May, 2014, were retrospectively analyzed. We estimated the chemotherapy response rate [complete response (CR) + partial response (PR)], clinical benefit rate [CR + PR+ stable disease (SD)], progression-free survival (PFS) and overall survival (OS), and evaluated treatment safety and toxicity reactions. Of the 4 patients, 1 achieved CR, with a disease-free survival time of 96 months; 1 achieved PR, with a PFS of 13 months and an OS of 25 months; 1 achieved SD, with a PFS of 9 months and an OS of 24 months; and 1 developed progressive disease, with a PFS of 3 months and an OS of 9 months. The response rate (CR+PR) was 50%, and the clinical benefit rate (CR+PR+SD) was 75%. Treatment-related adverse reactions occurred in all 4 patients, including bone marrow suppression and gastrointestinal reactions. Of the 4 patients, 1 developed grade 4 bone marrow suppression (thrombocytopenia), whereas the remaining 3 patients developed grade 2 bone marrow suppression (leukopenia). Of the 4 cases, 2 developed grade 2 gastrointestinal reactions, and the remaining 2 patients grade 1 gastrointestinal reactions. Therefore, BEV combined with chemotherapy was able to effectively control advanced or recurrent uterine sarcoma, was well-tolerated, and is considered to be a safe and effective candidate treatment for this type of tumor. PMID- 26893870 TI - Identification of DLC-1 expression and methylation status in patients with non small-cell lung cancer. AB - In order to determine whether the deleted in liver cancer-1 (DLC-1) gene is deregulated in non-small-cell lung carcinoma (NSCLC) and to assess the contribution of molecular alterations in DLC-1 to lung carcinogenesis, a total of 84 tissue specimens (30 NSCLC and 30 corresponding adjacent normal tissues; 5 benign tumor and 5 corresponding adjacent normal tissues; and 10 pulmonary bullae and 4 corresponding adjacent normal tissues), were obtained from 45 patients who underwent curative surgical resection. DLC-1 mRNA expression was evaluated by reverse transcription-quantitative polymerase chain reaction (PCR) and its protein level was assessed by western blot analysis. A significant downregulation of DCL-1 at the mRNA and protein levels was observed in NSCLC tissues when compared to benign lung tumors and normal lung tissues (P<0.001). To further determine whether the decreased expression of DLC-1 at the mRNA and protein levels is associated with the methylation of its promoter, methylation-specific PCR was performed following extraction of genomic DNA from the samples. DLC-1 promoter methylation was identified in 7 of the 30 (23.3%) NSCLC tissue samples, but not in the corresponding adjacent normal tissues from NSCLC patients or in lung tissues from non-NSCLC patients. Our data indicated that DLC-1 hypermethylation may play a crucial role in lung carcinogenesis and may be a target for the treatment of NSCLC. PMID- 26893871 TI - Symptoms at diagnosis as independent prognostic factors in retroperitoneal liposarcoma. AB - The prognostic factors of retroperitoneal liposarcoma have yet to be clearly determined due to its rarity, whereas the prognostic value of symptoms at diagnosis has never been evaluated to date. In this context, we reviewed 24 consecutive patients with primary retroperitoneal liposarcoma who underwent surgical resection with curative intent at our institution. The Kaplan-Meier analysis and the log-rank test were used to estimate progression-free survival (PFS; primary endpoint) and sarcoma-specific survival (SSS; secondary endpoint). The effect of various clinicopathological factors, including symptoms at diagnosis, on these two endpoints was assessed with a Cox proportional hazards model. During the study period, 11 patients (45.8%) developed recurrence after the initial surgery and 8 (33.3%) succumbed to retroperitoneal liposarcoma, with a median follow-up of 64 months. A total of 16 patients (66.7%) had symptoms at diagnosis, while the remaining 8 (33.3%) were diagnosed incidentally. The symptoms were palpability of the tumor (n=8); abdominal pain/fullness (n=3); flank pain/fullness (n=2); lower extremity pain (n=1); testicular pain due to varicocele (n=1); and discomfort on urination (n=1). Patients with symptoms at diagnosis were significantly more likely to develop recurrence (log-rank test, P=0.0196) and were also more likely to succumb to sarcoma (P=0.0778) compared with asymptomatic patients. On the multivariate analysis, symptoms at diagnosis and dedifferentiated components were independent predictors of poor PFS, while positive surgical margins were predictors of poor SSS. Given that symptoms at diagnosis are easily accessible for physicians, they may prove to be useful additional prognostic factors for primary retroperitoneal liposarcoma. PMID- 26893872 TI - Surgery following neoadjuvant chemotherapy for non-small-cell lung cancer patients with unexpected persistent pathological N2 disease. AB - Patients with mediastinal lymph node (LN) downstaging following neoadjuvant chemotherapy exhibit improved outcomes compared with patients with persistent N2 disease. The aim of this study was to compare clinicopathological characteristics and survival between patients with unexpected and expected persistent N2 disease following surgery for non-small-cell lung cancer (NSCLC). This retrospective analysis included 348 patients with NSCLC who underwent surgery following chemotherapy at the Shanghai Pulmonary Hospital, Tongji University School of Medicine, between 1995 and 2012. According to the results of the imaging examinations and postoperative pathology, the patients were divided into three groups, namely groups I (nodal downstaging, pN0-1), II (expected persistent N2 disease) and III (unexpected persistent N2 disease). The rates of overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify the independent risk factors for OS and DFS. The mortality rate was 1.1% during the postoperative period. Perioperative complications occurred in 45 patients (12.9%). The 5-year OS rate was 32.2, 6.3 and 25.9% in groups I, II and III, respectively (group I vs. III, P=0.023; and group III vs. II, P<0.001). The 5 year DFS rate was 30.1, 5.1 and 22.4% in groups I, II and III, respectively (group I vs. III, P=0.012; and group III vs. II, P<0.001). Grouping, predicted forced expiratory volume in 1 sec, N downstaging and skip N2 metastasis were identified as independent predictive factors associated with OS, whereas the independent risk factors associated with DFS were grouping and N downstaging. Patients with unexpected persistent N2 disease exhibited better survival compared with those with expected persistent N2 disease. Surgery following chemotherapy remains the optimal approach for a proportion of patients with persistent N2 disease. PMID- 26893873 TI - Capsule endoscopy in the diagnosis of an exophytic gastrointestinal stromal tumor in the small intestine of a young adult woman: A case report. AB - Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that mainly arise in the gastrointestinal tract. They are usually asymptomatic and are incidentally discovered during endoscopy or surgery. Diagnosis is confirmed by histological examination of the specimen. This is the case report of an asymptomatic GIST of the small intestine diagnosed by wireless capsule endoscopy. The tumor was initially suspected to be a leiomyoma, as GISTs in young adults are rare and are mainly discovered incidentally during colorectal cancer screening. The patient was a 35-year-old woman with occult gastrointestinal bleeding, with a normal medical history. An endoscopic assessment of the upper and lower GI tract (gastroscopy and colonoscopy) was performed, but did not reveal any abnormalities. Subsequently, an exophytic tumor initially suspected as leiomyoma or external pressure was detected in the small intestine by capsule endoscopy. A computed tomography scan was suggestive of a soft tissue tumor arising from the small intestine. A surgical specimen was obtained and the immunohistochemical examination revealed that the tumor was positive for CD117 and discovered on GIST 1 markers, while the markers of carcinoma, melanoma and lymphoma were negative, which was consistent with a diagnosis of a low-risk GIST with a mitotic count of <5/50 high-power fields. In this study, we aimed to present in detail the capsule endoscopic and radiological characteristics, as well as the findings of the histological examination of the surgical specimen. In conclusion, when occult blood is detected in the stool, even when gastroscopy and colonoscopy reveal no abnormal findings, small intestinal lesions should be suspected. Exophytic small intestinal GISTs, although rare, particularly in younger patients, they should be considered by physicians in the differential diagnosis of obscure GI bleeding of unknown origin, in order to reduce morbidity and mortality. Capsule endoscopy may be considered to be the first choice as a diagnostic tool for obscure GI bleeding. PMID- 26893874 TI - An assessment of interfractional bladder, rectum and vagina motion in postoperative cervical cancer based on daily cone-beam computed tomography. AB - Interfractional variations of the bladder, rectum and vagina may affect the accuracy of postoperative intensity-modulated radiotherapy in patients with cervical cancer. This study aimed to assess the interfractional variations with daily kV cone-beam computed tomography (CBCT). All the patients were instructed to control the filling status of the bladder and rectum. CBCT images were obtained daily after set-up and the bladder, rectum and vagina were contoured on each CBCT scan. All the contours were transferred to the planning CT following image fusion. Interfractional variations in pelvic organs were assessed with CBCT based on two reference lines, which were identified as A (the midsaggital line across the superior border of pubic symphysis) and B (a parallel line 1.5 cm above line A). The mean volume (range) of the bladder and rectum was 156.5 (1.7 626.5) and 48.2 (11.3-139.7) ml, respectively. The uniform planning target volume (PTV) margin of 10 mm failed to encompass the vagina in 17.3 and 18.1% of the fractions on lines A and B, respectively. The motion of the vagina (standard deviation) was 0.3 (0.3) and 0.1 (0.5) cm on lines A and B, respectively. The anteroposterior dimension and position of the vagina were significantly affected by the filling status of the bladder (P<0.05), but not by that of the rectum. Although instructions were given, the interfractional variations of the vagina and other pelvic organs were significant, which may exceed the uniform PTV margin; therefore, more effective methods to decrease these variations should be investigated. PMID- 26893875 TI - Recurrence patterns and risk factors following thoracoscopic esophagectomy with radical lymph node dissection for thoracic esophageal squamous cell carcinoma. AB - The aim of the present study was to clarify the therapeutic effect of thoracoscopic esophagectomy with radical lymph node dissection based on the recurrence pattern, and identify the risk factors for relapse-free survival in patients with esophageal cancer. The recurrence patterns in 140 patients who underwent complete thoracoscopic radical esophagectomy between January 2003 and December 2012 were investigated. The risk factors for recurrence were examined by univariate and multivariate analysis. Mediastinal recurrence in association with initial lymphatic metastasis was precisely analyzed. Esophageal cancer recurred in 49 (35.0%) of the 140 patients. The median recurrence time was 259 (45-2,560) days after the initial treatment. The patterns of initial recurrence among the 140 patients included hematological recurrence in 24 patients (17.1%), lymphatic recurrence in 26 (18.6%), pleural dissemination in 5 (3.6%), peritoneal dissemination in 2 (1.4%), and local recurrence in 4 (2.9%). Lymphatic recurrence within the mediastinal regional lymphatic stations occurred in only 8 (5.7%) of the 140 patients. Univariate analysis for relapse-free survival showed that the statistically significant variables were a tumor location in the upper third of the esophagus, stage of pT3 or pT4, presence of nodal metastasis, pStage of III or IV, presence of a residual tumor, performance of preoperative chemotherapy and performance of postoperative therapy. Multivariate analysis showed that only nodal metastasis and a positive residual tumor were statistically significant independent risk factors for relapse-free survival. Lymphatic recurrence within the mediastinum, particularly the station around the bilateral recurrent laryngeal nerves, was infrequent and independent of the initial metastatic distribution. Thoracoscopic esophagectomy with radical lymph node dissection provides favorable locoregional control. Lymphatic recurrence within the mediastinal regional nodes is infrequent and independent of the initial lymph node metastasis. A pathological residual tumor and lymph node metastasis are significant risk factors for recurrence. PMID- 26893876 TI - Cyclophosphamide combined with mitoxantrone and cytarabine is an effective salvage regimen for patients with acute myeloid leukemia who experienced primary induction failure or relapse. AB - Salvage regimens containing mitoxantrone have been successfully used for the treatment of primary induction failure or relapsed acute myeloid leukemia. However, the combination of cyclophosphamide with mitoxantrone and cytarabine (MAC) has never been assessed in these patients. A total of 91 patients, including patients with primary induction failure (n=44) and relapsed (n=47), were treated with a salvage MAC regimen, which consisted of mitoxantrone, cytarabine and cyclophosphamide. The overall complete remission rate was 74.7 (68/91) and 72.7% (32/44) for primary induction failure, and 76.6% (36/47) for relapsed patients. The overall survival rate and disease-free survival rate were 72.1 and 59.7% at 1 year, 42.9 and 47.1% at 3 years, and 36.7 and 43.0% at 5 years, respectively. Only one patient succumbed to mortality during induction therapy. The toxicity level was acceptable. Therefore, the present study demonstrated that MAC is a highly effective and well-tolerated regimen for salvage in patients experiencing primary induction failure or relapse. This treatment significantly improved the prognosis. PMID- 26893877 TI - Tyrosine kinase inhibitors improve parenchymal findings of liver cirrhosis in a patient exhibiting concomitant hepatocellular carcinoma and renal cell cancer. AB - Hepatocellular carcinoma (HCC) and renal cell cancer (RCC) are malignancies, which are chemotherapy resistant and fatal at the advanced stages. Previously developed tyrosine kinase inhibitors are used in the treatment of advanced stage disease. In the present case study, a patient using sunitinib for stage IV RCC presented with HCC following 2 years of treatment. A patient who exhibited Child Pugh class C cirrhosis initially, exhibited a marked improvement of hepatocellular parenchyma findings following treatment with sunitinib. Sunitinib is suggested to have preventive effects on the pathogenesis of liver fibrosis and cirrhosis in vitro, via an anti-vascular endothelial growth factor and anti platelet-derived growth factor mechanism. However, no clinical supportive study has been performed until now. Improvement of liver functions may be explained in this manner. Therefore, investigations are required with different doses of sunitinib and other tyrosine kinase inhibitors in order to evaluate the efficacy on treatment of cirrhosis progression. PMID- 26893878 TI - The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity. AB - The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan. PMID- 26893879 TI - Connexin subtype expression during oral carcinogenesis: A pilot study in patients with oral squamous cell carcinoma. AB - Gap junctional intercellular communication (GJIC) and connexin (Cx) expression were reported in association with carcinogenesis in various types of tumours. In an earlier histomorphometric study, the protein levels of Cx subtypes 26, 43 and 45 were differentially expressed in oral squamous cell carcinoma (OSCC), corresponding lymph node metastases and dysplasia-free oral mucosa. Moreover, membrane Cx43 acted as an independent prognostic marker in OSCC tissues. This study aimed to confirm the expression of described Cx subtypes at the mRNA level. Hence, a reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of Cx26, Cx43 and Cx45 gene expressions was performed in paired carcinoma and mucosa samples of 15 OSCC patients. Additionally, we assessed the interaction between Cx subtype expression and clinicopathological routine parameters. The RT-qPCR analysis revealed that Cx26 was downregulated in OSCC (P=0.01), while Cx43 was marginally upregulated in cancer tissue (P=0.04). Cx45 was significantly overexpressed in OSCC tissue compared with the intraoral mucosa controls (P<0.01), and remained unchanged at different tumour stages. No significant interactions between differential Cx subtype expression and clinicopathological routine parameters were observed. In conclusion, Cx regulation at the transcriptional level appears to be an early event during the initiation and development of OSCC, and is maintained during further progression. However, the mRNA-protein correlation is variable. This may be indicative of post transcriptional, translational and degradation regulations being associated with the determination of Cx protein concentration during oral carcinogenesis. PMID- 26893880 TI - Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy. AB - Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, >=200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose >=200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3 year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance. PMID- 26893882 TI - Improving the diagnosis of pulmonary embolism in the emergency department. AB - The diagnosis of pulmonary embolism (PE) in the emergency department is challenging due to the wide range of non-specific symptoms, lack of clinical diagnostic criteria, and imperfect investigations. Various scoring systems exist in an attempt to limit unnecessary investigations in those with low risk of PE. Following a baseline audit and subsequent PDSA cycles we implemented a flowchart for use in patients suspected of pulmonary embolism encouraging the correct use of the Wells Score and Pulmonary Embolism Rule out Criteria (PERC). The standard used for comparison was based on the NICE guidelines for diagnosis of PE with the addition that PERC could also be used if appropriate. Data was collected over four week periods before and after the introduction of our flowchart in two emergency departments in Melbourne. We aimed to increase documentation of pre test probability, reduce inappropriate investigations, and increase the use of interim parenteral anticoagulation where there was a delay to imaging. Results showed an increase in the documentation of pre-test probability and the proportion of investigations requested that were inappropriate was reduced. The percentage of inappropriate d-dimers was reduced from 36% to 24%; the percentage of inappropriate CTPAs was reduced from 34% to 10%; and the percentage of inappropriate V/Q scans was reduced from 42% to 14%. Implementation of a simple diagnostic algorithm led to an increase in documentation of pre-test probability and a reduction in inappropriate and unnecessary investigations. This intervention may be applicable to other emergency departments where similar issues in diagnosing pulmonary embolism exist. PMID- 26893881 TI - Anastomosing hemangioma: The first case report in the bladder. AB - A rare neoplasm, termed 'anastomosing hemangioma' (AH), has been previously described in the genitourinary tract. To date, 29 cases of AH have been reported in the literature, and the case reported in the present study is, to the best of our knowledge, the first AH described in the urinary bladder. It is essential to distinguish AH from malignant vascular tumors due to the different treatments required and the prognosis. The patient in this case study was asymptomatic, with a neoplasm of ~1 cm within the right wall of the bladder. Pathologically, the lesion was predominantly composed of a structure comprising a small vascular cavity and irregularly fenestrated anastomosing vascular channels, with no clear atypia of the endothelial cells. PMID- 26893883 TI - Using visual prompts to aid analgesia prescribing. AB - Analgesia prescribing is fundamental to a patient's journey, affecting length of stay and patient experience. Laminated prompts are used throughout the NHS Foundation Trust to aid doctors prescribing. A baseline questionnaire was carried out to gather doctors' prescribing habits and current ability to convert opioids to their morphine equivalent. Ninety three percent of doctors said they were moderately to extremely confident when prescribing analgesia. However, when asked to carry out a simple opioid conversion only 14% answered correctly. Eighty three percent of doctors said they were prescribing laxatives alongside opioids frequently (57%) or almost all the time (25%). When actual rates were sampled only 14% of patients were prescribed a concurrent laxative. Laminated pain management guideline cards were created and distributed to doctors at sign in for weekly teaching. Doctor interviews were carried out to see if they were in possession of a prompt card and a simple opioid conversion question was asked. If they did not have a prompt card at the time of interview they were issued with one after answering the conversion question. Rates of concurrent laxative prescribing were collected from the electronic prescribing record of patients on the acute medical unit. Posters were displayed in doctors' offices and drug rooms. Laxative prescribing rates were re-collected and compared with the survey responses. Distribution of laminated prompts increased accuracy of opioid conversion by 86%. Error rates fell as prompt prevalence increased until there was 100% prevalence and 0% error. Concurrent prescribing of laxatives increased to 50% after posters were displayed around the acute medical unit. Doctors reported they were confident when prescribing analgesia. They reported that they often prescribed concurrent medications, however this did not relate to actual prescribing practices. Visual prompts improved doctors analgesia conversion knowledge and prescribing practices. Laminated prompt cards are now incorporated in new doctors' induction packs. PMID- 26893884 TI - Targeted case finding for dementia in primary care: Surrey Downs dementia diagnosis project. AB - Currently less than half of the estimated number of people with dementia in England receive a formal diagnosis of dementia or have contact with specialist dementia services. Case finding focused on high risk groups may be an effective way to identify the undiagnosed. This joint Surrey Downs Clinical Commissioning Group and Surrey and Borders NHS Foundation Trust quality improvement project aimed to increase the rate of dementia diagnosis across Surrey Downs using specialist link nurses (SLNs). Thirty three GP surgeries covering the entire Surrey Downs area took part in the project. Individuals at high risk of developing dementia were identified from GP electronic disease registers, and were offered screening at their GP practices by SLNs, using a combination of mini cognitive test (Mini-Cog) and functional assessment questionnaire (FAQ). Suitable individuals who screened positive were seen by their GP and where appropriate referred to secondary care services for further evaluation. Based on the presence of risk factors, 6657 (11.9%) people were identified from a total population of 55 845 over 65s, and 1980 (29.7%) completed the screening assessment. Three hundred and fifty eight (18.1%) individuals screened positive and were referred to their GP, who referred 205 (57.2%) of them to the memory services for further assessment. Of those referred, 164 (80%) had a comprehensive specialist assessment. Forty one (20%) declined further assessment, and their GPs were informed. The mean age of the cohort who completed the comprehensive assessment was 82.3 years (SD=4.26), and were predominantly white and male. Fifty four (32.9%) had mild cognitive disorder (MCD), and 101 (61.6%) patients were diagnosed with dementia. The most common dementia was mixed type (43; 42.6%), followed by Alzheimer's dementia (32; 31.7%). The most common risk factor among patients with cognitive impairment (MCD or dementia) was hypertension (69; 44.5 %), followed by ischemic heart disease (64, 41.3%). Nurse led case finding for cognitive impairment in a high risk population identifies people with dementia who are not yet formally diagnosed. The combined use of brief instruments to assess cognitive functioning and functional capabilities is helpful in identifying individuals with possible dementia. PMID- 26893885 TI - Improvement of fluid balance monitoring through education and rationalisation. AB - Fluid input/output charts in hospital inpatients are a valuable source of information for doctors reviewing intravenous fluid prescription, but are notorious for being incomplete and inaccurate. Lack of awareness of the importance of fluid balance amongst nursing staff and an excess of unnecessary monitoring are two factors contributing to the problem. We conducted a quality improvement project on the respiratory ward in a large district general hospital aiming to specifically address these two factors. Pre-intervention audit showed that only 53% of input/output monitoring was clinically indicated, with an average chart completion of 50%. Using e-Learning and verbal presentation to raise awareness around fluid balance, we implemented a new system whereby daily medical review of charts lead to rationalisation of monitoring. Post-intervention audit showed a 93% reduction in unnecessary monitoring, with corresponding increases in completion (40%) and accuracy (48%) of remaining charts. In conclusion, education has enabled a culture change on the ward that has drastically increased the quality of fluid balance monitoring. PMID- 26893886 TI - Reduction of referral to assessment time for an older adults community mental health team. AB - Anecdotal evidence suggested that waiting times within the older adults community mental health team (OA CMHT) had been increasing over time. An assessment and evaluation was indicated to ensure best quality care was provided for patients. A comparison was made between waiting times in January to December 2011 compared with August 2013 to July 2014. In 2011 the mean number of days until initial assessment from the point of referral was 12 days for routine cases, and 3.6 days for urgent cases. The re-audit showed the number of days increased to 15.89 days for routine cases, and 9.81 days for urgent cases. Contributory factors were reviewed, and it was felt that to address this problem, a duty worker role was necessary. The role of the duty worker was divided into triaging and allocating work. The triaging process was to ensure all urgent cases were highlighted early and acted upon. The duty worker's role was also to gather sufficient information from the referrer, to reduce the risks of inadequate knowledge delaying assessment. In addition, the allocating process required the duty worker to designate a clinician in charge of the case upon receipt of referral. This ensured that clinicians were able to offer the earliest possible appointment slot for the initial assessment, and thus reduce waiting times. Following implementation, findings from September 2014 to February 2015 showed an improvement in average waiting times, as well as an improvement in the percentage of assessments reviewed within previously set standards. For routine reviews, the mean time until assessment was 10.68 days. For urgent reviews, the mean time until initial assessment was 6.8 days. However, it was noted that majority of urgent reviews were still not being reviewed in time. The outcomes of this study demonstrated an improvement of both waiting times, and percentage of patients being seen within set standards following a single intervention. In the current climate of cost efficiency savings, it is important for services to continue to find ways to streamline and improve upon current practices, to ensure the best outcome for patients. PMID- 26893887 TI - Improving information availability in vascular surgical clinics. A service evaluation and improvement project. AB - This prospective service evaluation was designed to assess the availability of critical information required in vascular surgical clinics. All the data was collected via a repeated questionnaire, and the outcomes from each cycle were used to highlight where intervention was required to improve the surgical clinic experience. The first audit identified outpatient clinic deficiencies and allowed for problem analysis. Two Plan-Do-Check-Act (PDCA) cycles then were undertaken. Interventions following each cycle included consultant access to online duplex scans and secretarial access to referral letters. Results from the first cycle showed that approximately 20% of clinic appointments were missing information and only 30% of these issues were resolved during the clinic using a work around. Following the first intervention; the numbers of missing patient notes reduced to 4.3% (10.5%), and referral letters to 3.6% (4.6%). Although the numbers of missing duplex scan results increased to 6.5% (3.3%), the new system of online scan results allowed for all scans to be accessed during the clinic. Following results of a second PDCA cycle, vascular surgical secretaries were given access to 'choose and book', a database of GP referral letters. Post intervention, all missing referral letters (2%) could be accessed immediately within the clinic setting. Data driven interventions and repeated PDCA cycles can improve hospital systems for minimal cost. With an annual clinic turnaround of 2500 patients, these interventions can reduce clinic delays and potential harm caused by unavailable records for up to 500 patients a year. PMID- 26893889 TI - Reducing the overuse of betahCG measurements in the emergency gynaecology clinic. AB - Serial betahCG testing can be a helpful tool in deciding how to manage pregnancy of unknown location. Its use in emergency gynaecology clinics can prevent unnecessary admission and intervention. However, despite NICE Guidelines on when it is safe to opt for conservative management, it was identified that there was a problem with over-testing of betahCG when patients could be discharged with instructions to repeat a urinary pregnancy test in two weeks. Two PDSA cycles were undertaken to improve the awareness of NICE guidelines: the first involved formal and informal educational sessions and the second involved the inclusion of a guideline summary on the front of patients' notes when they were having serial betahCG tests for doctors to refer to. Case notes were reviewed for 157 women who had betahCG tests at baseline and 48 hours. Of these, 139 were suitable for serial betahCG testing, and 83 of these were suitable for discharge after 48 hours. Of the 83 patients that were eligible for discharge, there were 31 unnecessary betahCG tests done, 23 of which were prior to intervention. A significant improvement was noted, with between 4-10 unnecessary betahCG tests per fortnight prior to intervention, 0-3 following the first intervention, and 0 2 following the second. Reduction in unnecessary betahCG testing has positive implications for patients, who do not have to take unnecessary time off work, prolong an already very distressing period, and have unnecessary blood tests. There are also cost and time saving implications for the hospital. PMID- 26893888 TI - Importance of patient-centred signage and navigation guide in an orthopaedic and plastics clinic. AB - Gulshan & Nanji Orthopaedic and Plastics Center at the North York General Hospital is the second busiest site after the emergency department serving more than 26,000 patients annually. Increase in patient flow, overworked staff, and recent renovations to the hospital have resulted in patients experiencing long wait times, and thusly patient dissatisfaction and stress. Several factors contribute to patient dissatisfaction and stress: i) poor and unfriendly signage; ii) inconsistent utilization of the numbering system; and iii) difficulty navigating to and from the imaging center. A multidisciplinary QI team was assembled to improve the patient experience. We developed a questionnaire to assess patient stress levels at the baseline. Overall, more than half of the patients (54.8%) strongly agreed or agreed to having a stressful waiting experience. Subsequently, based on patient feedback and staff perspectives, we implemented two PDSA cycles. For PDSA 1, we placed a floor graphic (i.e. black tape) to assist patients in navigating from the clinic to the imaging centre and back. For PDSA 2, we involved creating a single 21"*32" patient-friendly sign at the entrance to welcome patients, with clear instructions outlining registration procedures. Surveys were re-administered to assess patient stress levels. A combination of both interventions caused a statistically significant reduction in patient stress levels based on the Kruskal-Wallis and Mann-Whitney U Tests. The present project highlighted the importance of involving stakeholders as well as frontline staff when undertaking quality improvement projects as a way to identify bottlenecks as well as establish sustainable solutions. Additionally, the team recognized the importance of incorporating empirical based solutions and involving experts in the field to optimize results. The present project successfully implemented strategies to improve patient satisfaction and reduce stress in a high flow community clinic. These endpoints were achieved by incorporating patient friendly signage, as well as improving patient flow directors. PMID- 26893891 TI - Introduction of a junior doctors' handbook: an essential guide for new doctors. AB - The transition period for new junior doctors is a daunting and challenging time, as vast amounts of information specific to each hospital, ward, and job must be learnt while maintaining patient care standards.[1] In NHS Tayside, Scotland, tips and guidance for each job are informally handed over from previous junior doctors to the next, resulting in an unreliable and unsustainable handover of information. Time must then be spent by new doctors learning the intricacies and practicalities of their new job, rather than spending time focusing on patient care. Our aim was to improve this transition period for new junior doctors to NHS Tayside through the creation and implementation of a junior doctors' handbook, which would provide information and practical advice on day to day life as a junior doctor. We hoped to implement this project by August 2015 to coincide with the arrival of these new doctors to NHS Tayside. Through repeat PDSA cycles we created a sustainable and reliable junior doctors' handbook, containing a centralised hub of information for doctors that was accessible through our health board's website. The junior doctors' handbook has been a highly beneficial resource that has been praised for its detailed information on all aspects of day to day life for doctors in NHS Tayside. Feedback also demonstrated that doctors felt the junior doctors' handbook had improved their efficiency. Our hope is that this project can continue to be developed within our hospital, but also to be used as an idea outside our health board to improve the transition period for new doctors on a wider scale. PMID- 26893890 TI - Improving residents' handovers through just-in-time training for structured communication. AB - In a recent quality assurance project we learned that nearly half of the handovers we examined were characterized as unsatisfactory by our residents, who provided examples in which their anxiety had been piqued and patient care had been affected. These reports substantiated a growing body of literature on the relationship between the quality of handover and the quality of patient care, so we sought to improve the quality and consistency of the in-hosptial handovers undertaken by our internal medicine residents. Senior residents attended morning report for three consecutive month long blocks and evaluated the quality of the handovers using an observational protocol comprised of 16 aspects of effective handover. During the first block, the resident observed a median of eight of the 16 practices occurring across the 46 handovers, and a large amount of variability. At the beginning of the subsequent block we presented a concise introduction to a structured handover procedure (SBARR). The median quality of the subsequent 33 handovers rose to 11, and the variability decreased considerably. In the next block we refined the SBARR orientation to focus on the errors observed in the previous blocks, and the improvement in the quality and variability was sustained. The minor change, which requires few resources to sustain, had a favourable impact on the quality of our residents' in-hospital handovers. PMID- 26893892 TI - Improving Documentation and Communication Using Operative Note Proformas. AB - Accurate and detailed documentation of surgical procedures is part of good clinical practice, set out by the General Medical Council (GMC). Knee arthroscopy often involves large data sets which require accurate documentation for future assessment and management. This study assesses the quality of documentation of knee arthroscopy, followed by an evaluation of the implementation of a novel operative proforma. A review of 30 consecutive knee arthroscopy operation notes were analysed for missing information, set against a standardised 30 point criteria. An operation proforma was then introduced, and a further 30 consecutive knee arthroscopy operation notes were analysed. We evaluated allied health professional satisfaction with a Likert point scale survey of 21 allied healthcare professionals (recovery and ward nurses, and physiotherapists) following introduction of the proforma. The mean number of missing items on a 30 point scale was 8.8 (range 0 to 23). Examination under anaesthesia was missed in 43% of cases, tourniquet time in 37% of cases, and wear results in 17% of cases. Following introduction of the proforma, the mean number of missing items was 1.1 (range 0 to 24; p <0.001). This rose to 3.8 after one year (p <0.001) before improvement to 0.7 (p <0.01) with a new and improved proforma. Eighty percent strongly agreed the operation note was clearer, 90% strongly agreed it was more legible, 90% strongly agreed it was more understandable, 50% strongly agreed there was more information recorded, and 100% strongly agreed on the proforma having been improved. Knee arthroscopy is a common procedure with large data sets, which can often be missed or incomplete. A standardised proforma results in a statistically significant improvement in documentation and reduces the incidence of missing information. They are subjectively clearer, more legible, and generally better compared with handwritten notes. This study demonstrates the improvements in healthcare documentation, both clinically and legally, following introduction of a simple proforma. This concept should be applicable to different specialities and procedures in healthcare. PMID- 26893893 TI - Low stimulus environments: reducing noise levels in continuing care. AB - In the low stimulus environment project, we aimed to reduce the levels of intrusive background noise on an older adult mental health ward, combining a very straightforward measure on decibel levels with a downstream measure of reduced distress and agitation as expressed in incidents of violence. This project on reducing background noise levels on older adult wards stemmed from work the team had done on reducing levels of violence and aggression. We approached the problem using quality improvement methods. Reducing harm to patients and staff is a strategic aim of our Trust and in our efforts we were supported by the Trust's extensive programme of quality improvement, including training and support provided by the Institute for Healthcare Improvement and the trust's own Quality Improvement team. Prior to the project we were running a weekly multi disciplinary quality improvement group on the ward. We established from this a sub-group to address the specific problem of noise levels and invited carers of people with dementia on our ward to the group. The project was led by nursing staff. We used a noise meter app readily downloadable from the internet to monitor background noise levels on the ward and establish a baseline measure. As a group we used a driver diagram to identify an overall aim and a clear understanding of the major factors that would drive improvements. We also used a staff and carer survey to identify further areas to work on. Change ideas that came from staff and carers included the use of the noise meter to track and report back on noise levels, the use of posters to remind staff about noise levels, the introduction of a visual indication of current noise levels (the Yacker Tracker), the addition of relaxing background music, and adaptations to furniture and environment. We tested many of these over the course of nine months in 2015, using the iterative learning gained from multiple PDSA cycles. The specific aim was a decrease from above 60dB to below 50dB in background noise on the wards. Following our interventions, we have managed to decrease noise levels on the ward to 53dB on average. The success of this project to date has relied on the involvement of ward staff and carers - those most affected by the problem - in generating workable local solutions. As many of the change ideas amounted to harm free interventions it was easier for us to make a case to test them out in the real-life setting. Nevertheless we were surprised at how effective such seemingly simple ideas have been in improving the environment on the ward. We have incorporated the change ideas into routine practice and are advising other wards on similar projects. PMID- 26893894 TI - Improving the quality of operative notes by implementing a new electronic template for upper limb surgery at the Royal Derby Hospital. AB - The RCS has published clear and succinct guidelines dictating the necessity for the documentation of legible and timely surgical operative notes and exactly what should be included. A baseline study within the upper limb unit at our trust showed a 71.1% adherence with the RCS guidelines with an average delay of typing of notes after dictation was 11.6 days. This quality improvement project designed and developed a bespoke electronic surgical notes template built within an existing database driven software within the Trust. After implementation of the templates we found no delays in full operative notes being typed and a 100% adherence with the RCS guidelines. This project significantly improved the quality and timely production of electronic surgical notes within a sustainable electronic software solution. PMID- 26893895 TI - Availability of ambulance patient care reports in the emergency department. AB - Clinical handovers of patient care among healthcare professionals is vulnerable to the loss of important clinical information. A verbal report is typically provided by paramedics and documented by emergency department (ED) triage nurses. Paramedics subsequently complete a patient care report which is submitted electronically. This emergency medical system (EMS) patient care report often contains details of paramedic assessment and management that is not all captured in the nursing triage note. EMS patient care reports are often unavailable for review by emergency physicians and nurses. Two processes occur in the distribution of EMS patient care reports. The first is an external process to the ED that is influenced by the prehospital emergency medical system and results in the report being faxed to the ED. The second process is internal to the ED that requires clerical staff to distribute the fax report to accompany patient charts. A baseline audit measured the percentage of EMS patient care reports that were available to emergency physicians at the time of initial patient assessments and showed a wide variation in the availability of EMS reports. Also measured were the time intervals from patient transfer from EMS to ED stretcher until the EMS report was received by fax (external process measure) and the time from receiving the EMS fax report until distribution to patient chart (internal process measure). These baseline measures showed a wide variation in the time it takes to receive the EMS reports by fax and to distribute reports. Improvement strategies consisted of: 1. Educating ED clerical staff about the importance of EMS reports 2. Implementing a new process to minimize ED clerical staff handling of EMS reports for nonactive ED patients 3. Elimination of the automatic retrieval of old hospital charts and their distribution for ED patients 4. Introduction of an electronic dashboard for patients arriving by ambulance to facilitate more efficient distribution of EMS reports. Implementation of change strategies did not result in a significant improvement in the percentage of EMS reports available to emergency physicians at the time of initial patient assessment. However, tracking both external and internal processes that influence EMS report availability showed the internal process time from fax report receipt to distribution significantly improved. This improvement reflected the change strategies that were all directed at improving the internal process. EMS patient care reports are more efficiently processed and distributed in the ED due to change strategies implemented that targeted the ED's internal process of EMS report distribution. The external process responsible for transmitting EMS reports to the ED is the limiting factor that prevents consistent timely access of EMS reports by emergency physicians and will require dedicated improvement strategies. PMID- 26893896 TI - Reducing calls missed by the hospital telephone exchange from 26% to less than 10. AB - A hospital's telephone exchange is the first point of contact for patients and their attendants to take appointments, to collect healthcare related information and to connect to the hospital in case of emergencies. At Sitaram Bhartia Institute of Science and Research the doctors, patients, and attendants often complained about the inefficiency of the hospital exchange. In February 2012, a doctor raised her concern of calls not being picked up at the exchange with the senior management and a QI project was initiated to tackle the problem. Baseline data showed that about 26% of incoming calls to the hospital during 8am to 8pm were not being picked up. On the basis of the baseline data, call audits, staff interviews, and observations the project team identified the defects. These defects were categorized under four headings - manpower, equipment, processes, and environment. The team proposed several change ideas. Some of these change ideas were implemented immediately. Three proposed change ideas were tested through individual PDSA cycles. The percentage of missed calls dropped from 26% to 18.1% after the first cycle and then to 9.6% and 6.5% after the subsequent cycles which involved testing of two other additional change ideas. These changes were implemented and a benchmark of no more than 10% calls to be missed was set. For nearly three years we have held the gains and have met the benchmark of missing not more than 10% calls coming to the hospital exchange between 8am to 8pm. The contributing factors to the success have been the involvement of frontline workers, an expert and engaged head of department, and senior leadership support. PMID- 26893897 TI - Raising the issue of DNAR orders in vascular surgery patients. AB - The Tracey Report has recently raised the status of Do Not Attempt Cardio Pulmonary Resuscitation (DNACPR) orders in the hospital setting.[1] Guidelines are in place both nationally and locally to provide advice to clinicians on when to discuss DNACPR, and the approach to be taken. There was concern that on a busy regional vascular surgery unit, discussion of resuscitation status was not regular practice. Consequently, some patients were at risk of being inappropriately resuscitated, particularly out of hours. The North Bristol Somerset and Gloucester DNAR decision tree[2] was the tool used to decide whether a patient should have a documented discussion and/or a DNACPR form completed. We correlated the outcome of the decision tree with the presence of a DNACPR form or documented resuscitation discussion. Baseline measurements from all vascular inpatients on the vascular surgery unit demonstrated that only 27% had a DNACPR form or documented discussion in concordance with the DNACPR Decision Tree outcome. The aim of this project was to increase the proportion of patients with concordance of the DNACPR decision tree outcome with documented discussion or DNACPR form. The following three simple interventions raised concordance from 27% to 64% of patients on the vascular surgery unit. 1. Including resuscitation status of each patient as a column in the doctors daily handover. 2. Posters in staff only areas to highlight the meaning of DNACPR and raise awareness of the DNACPR decision tree. 3. Educational meeting surrounding DNACPR with the vascular surgery consultants, led by a care of the elderly consultant . This project has highlighted how raising awareness around DNACPR increases discussion amongst the clinical team surrounding resuscitation status of a patient. Consequently, this enables discussion to be had with patient and their family. PMID- 26893898 TI - Antimicrobial stewardship: Improving antibiotic prescribing practice in a respiratory ward. AB - International efforts have mandated guidelines on antibiotic use and prescribing, therefore the focus is now on encouraging positive behavioral changes in antibiotic prescribing practice. Documentation of indication and intended duration of antibiotic use in drug charts is an evidence-based method of reducing inappropriate antibiotic prescribing. It is also a standard detailed in our local antimicrobial guidelines. We collected baseline data on compliance with documentation of indication and duration in drug charts in a respiratory ward which revealed compliance rates of 24% and 39% respectively. We introduced interventions to improve accessibility to the guideline and to increase awareness by distributing antibiotic guardian pocket cards with a three-point checklist and strategically-placed mini-posters. We also aim to increase team motivation by obtaining their feedback in multidisciplinary team meetings and by introducing certificates for their involvement in the quality improvement process. The results of the second cycle post-intervention showed an increase in compliance rates for documentation of indication and duration of 97% and 69% respectively. After a further awareness and discussion session at the multidisciplinary team meeting with the local antimicrobial management team audit nurses, a third cycle showed compliance rates of 94% and 71% for indication and duration respectively. This project has highlighted the importance of improving accessibility and of encouraging interventions that would bring about a change in personal value and subsequently in behavior and individual practice. PMID- 26893899 TI - Analgesia in hip fractures. Do fascia-iliac blocks make any difference? AB - Despite recent national advances in the care for the hip fracture patient, significant morbidity and mortality persists. Some of this morbidity is attributable to the analgesia provided in the hospital setting. The National Institute of Health and Care Excellence and the Association of Anaesthetists of Great Britain and Ireland recommend the use of simple oral analgesia including opioids, with fascia-iliac blocks (FIB) used as an adjunct. Literature review reveals a paucity of evidence on this. The aim of this project was to evaluate the proportion of patients receiving a fascia-iliac block prior to operative intervention. A secondary aim was to evaluate the efficacy of these blocks through analysis of pre and post-operative opioid usage, post-operative delirium, time to bowel opening, and naloxone use. Patients who received a fascia-iliac block received significantly less post-operative and total analgesia (p=0.04, p=0.03), had lower rates of delirium (p=0.03) and those patients which were discharged directly home had a shorter inpatient stay (p=0.03). No patients who received a fascia-iliac block (FIB) needed naloxone to reverse opioid toxicity, whilst two without fascia-iliac block did. The results of the project eventually led to the introduction of a hip fracture care pathway which incorporates a single shot fascia-iliac block for all patients who are eligible. Within a two year study period, compliance with fascia-iliac blocks improved from 54% to 90%. Our experience shows a great improvement in compliance with fascia-iliac blocks in the pre-operative period. This work has also underpinned the introduction of a new hip fracture care pathway ultimately to better patient care and outcomes. PMID- 26893900 TI - Improving the inspection and manual cleaning of dental instruments in a dental hospital. AB - Within the dental hospital setting, it is a frequent occurrence to find residual cement contaminating instruments in a newly opened kit having undergone the decontamination cycle. Any instrument found to be contaminated then cannot be used, as the area underneath the cement is not sterile. This in itself has several repercussions. These include: cross-contamination, since there is a chance that the cement will be removed and the contaminated instrument used; cost, as each new kit that will be opened due to contaminated instruments will incur decontamination costs; and finally time, which most importantly has an impact on patient experience. Our baseline data recording focussed on finding out the severity of the problem, which instruments were most affected, and how this affected patient treatment, using a questionnaire. Within the paediatric department, 27% of examination kits contained a contaminated instrument, almost one third of all kits used. This quality improvement project utilized a poster and team huddle discussions to raise awareness of the problem and successfully reduced the number of contaminated instrument kits to 7% over a period of four weeks. PMID- 26893901 TI - A quality improvement project to tackle under-reporting of hazards by doctors by using an anonymous telephone hotline. AB - An anonymous hazard reporting hotline was established for doctors to use on two general medical wards at Weston General Hospital (WGH) in North Somerset in England during an eight day period in July/August 2014. Doctors were encouraged to report hazards and near misses or just start a conversation about a concern. The existing computer based significant event system remained alongside the hotline and was to be used where actual harm had come to a patient. A team of consultants and quality improvement administrators monitored the hotline on a daily basis, categorized the level of risk being reported and ensured, where possible, that action was taken to address the doctors' concerns. The hotline increased reporting rates from two per month to 25 in eight days. The system identified 13 amber (medium risk) and five red (high risk) hazards which would otherwise not have been known about. This author believes these five high risk reports alone make the case for a new, quicker, easier, and anonymous reporting system for doctors at WGH urgent and irrefutable. PMID- 26893902 TI - Profiling of Alzheimer's disease patients in Puerto Rico: A comparison of two distinct socioeconomic areas. AB - OBJECTIVE: The Latino/Hispanic community in the United States is at higher risk of developing Alzheimer's disease than other ethnic groups. Specifically, Caribbean Hispanics showed a more severe Alzheimer's disease symptomatology than any other ethnic group. In a previous study, we demonstrated that the mortality rate associated with Alzheimer's disease in Puerto Rico is higher than that reported in the United States. Moreover, the mortality rate associated with Alzheimer's disease was higher among Puerto Rican living in Puerto Rico than those in the mainland United States. There is also a differential geographical distribution of mortality rate associated with Alzheimer's disease in Puerto Rico, which may be associated with differential socioeconomic status and/or access to healthcare. However, there is no information regarding the clinical profile of Alzheimer's disease patients in Puerto Rico. METHODS: Here, we present the results of a retrospective study directed to profile Alzheimer's disease patients clustered into two groups based on areas previously determined with low (Metro Region) and high (Northwest-Central Region) mortality rate associated with Alzheimer's disease in Puerto Rico. RESULTS: Significant difference in the age-at diagnosis and years of education was found among patients within the two studied regions. Despite these differences, both regions showed comparable levels of initial and last Mini Mental State Examination scores and rate of cognitive decline. Significant difference was also observed in the occurance of co morbidities associated with Alzheimer's disease. CONCLUSIONS: The differential profile of Alzheimer's disease patients correlated with differences in socioeconomic status between these two regions, suggesting that covariant associated with social status may contribute to increased risk of developing Alzheimer's disease. Further studies should be conducted to determine the role of socioeconomic factors and healthy living practices as risk factors for Alzheimer's disease. PMID- 26893904 TI - Home-range use patterns and movements of the Siberian flying squirrel in urban forests: Effects of habitat composition and connectivity. AB - BACKGROUND: Urbanization causes modification, fragmentation and loss of native habitats. Such landscape changes threaten many arboreal and gliding mammals by limiting their movements through treeless parts of a landscape and by making the landscape surrounding suitable habitat patches more inhospitable. Here, we investigate the effects of landscape structure and habitat availability on the home-range use and movement patterns of the Siberian flying squirrel (Pteromys volans) at different spatial and temporal scales. We followed radio-tagged individuals in a partly urbanized study area in Eastern Finland, and analysed how landscape composition and connectivity affected the length and speed of movement bursts, distances moved during one night, and habitat and nest-site use. RESULTS: The presence of urban habitat on movement paths increased both movement lengths and speed whereas nightly distances travelled by males decreased with increasing amount of urban habitat within the home range. The probability of switching from the present nest site to another nest site decreased with increasing distance among the nest sites, but whether the nest sites were connected or unconnected by forests did not have a clear effect on nest switching. Flying squirrels preferred to use mature forests for their movements at night. CONCLUSIONS: Our results suggest that the proximity to urban habitats modifies animal movements, possibly because animals try to avoid such habitats by moving faster through them. Urbanization at the scale of an entire home range can restrict their movements. Thus, maintaining a large enough amount of mature forests around inhabited landscape fragments will help protect forest specialists in urban landscapes. The effect of forested connections remains unclear, highlighting the difficulty of measuring and preserving connectivity in a species-specific way. PMID- 26893903 TI - Double-layered hyaluronic acid/stearic acid-modified polyethyleneimine nanoparticles encapsulating (-)-gossypol: a nanocarrier for chiral anticancer drugs. AB - This study aimed to enhance the water solubility and antitumor efficacy of (-) gossypol. Polyethyleneimine conjugated with stearic acid (PgS) was used for loading and protecting (-)-gossypol through hydrogen bonding. Double-layered hyaluronic acid (HA)-modified PgS nanoparticles encapsulating (-)-gossypol [(-)-G PgSHAs] were prepared through a two-step fabrication process. The nanoparticles possessed a uniform spherical shape with a dynamic size of 110.9 +/- 2.4 nm, which was determined through transmission electron microscopy and dynamic light scattering analysis. The encapsulation efficiency and drug-loading capacity of ( )-G-PgSHAs were 72.6% +/- 3.1% and 9.1% +/- 0.42%, respectively. The IR spectra of the samples confirmed the protection effect of hydrogen bonding on the optical activity of the encapsulated (-)-gossypol. (-)-G-PgSHAs exhibited a controlled and tumor-specific release because of the high expression of HAase in the tumor region. The tumor-targeting feature of PgSHAs due to HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near infrared fluorescence imaging. The in vitro test showed that the (-)-G-PgSHAs had similar cytotoxicity to free ( )-gossypol and was smaller than that of the encapsulated (+/-)-gossypol [(+/-)-G PgSHAs]. The in vivo study of the anti-cancer effect of (-)-G-PgSHAs revealed that (-)-G-PgSHAs had a more enhanced tumor-suppression effect and reduced systemic toxicity compared with free (-)-gossypol and (+/-)-G-PgSHAs (P < 0.05). Therefore, PgSHA was a useful (-)-gossypol nanocarrier that exhibits high biocompatibility, tunable release of drug, and tumor-targeting characteristics for cancer treatment. In addition, this double-layered nanocarrier provided novel strategies for the encapsulation of other chiral drugs. PMID- 26893905 TI - Semen quality of 4480 young cancer and systemic disease patients: baseline data and clinical considerations. AB - BACKGROUND: Except for testicular cancer and Hodgkin's disease, baseline data on semen quality in case of cancers as well as systemic pathologies of the young adult are scarce or based on low sample size. METHODS: Semen quality in patients having testicular cancer (TGCT, n = 2315), Hodgkin's disease (HD, n = 1175), non Hodgkin's lymphoma (NHL, n = 439), leukemia (L, n = 360), sarcoma (S, n = 208), brain tumour (BT, n = 40), Behcet's disease (Behcet's, n = 68) or multiple sclerosis (MS, n = 73) was studied and compared to that of 1448 fertile men candidates for sperm donation (CSD) and 208 partners of pregnant women (PPW). All samples were studied following the same methodology in a single laboratory. Post freezing and thawing semen characteristics were also studied. RESULTS: The percentage of normozoospermic men was only 37 % for L patients and lower than 60 % for TGCT, NHL, S and BT. The level of sperm production was differently decreased according to pathologies, the median total sperm count in TC and L patients being four times lower (p < 0.01 when compared to CSD and PPW). The lowest percentage of progressively motile spermatozoa was found for L and BT patients (both, p < 0.01 compared to CSD and PPW). The percentage of morphologically normal spermatozoa was also reduced in cancer patients, especially in BT patients. Progressive motility after thawing in patients was about half that observed among candidates for sperm donation. In almost half of the semen of patients with testicular cancer or leukemia, the total number of motile spermatozoa per straw was less than 0.5 * 10(6) compared to 4.3 * 10(6) in CSD. CONCLUSIONS: The present data confirm on large series the deleterious impact of various cancers of the young adult on semen quality, establishing thus baseline data for future studies. Owing to the post-thaw quality of the frozen straws, future fertility projects for the majority of the patients studied (in case there is no post-treatment recovery of spermatogenesis) should necessitate an ICSI to provide the best chance of paternity whatever the fertility check-up in the female partner. PMID- 26893907 TI - Erratum to: A retrospective study to identify risk factors for somnolence and dizziness in patients treated with pregabalin. AB - [This corrects the article DOI: 10.1186/s40780-015-0022-7.]. PMID- 26893906 TI - Circulating nucleosomes as predictive markers of severe acute pancreatitis. AB - BACKGROUND: The components of nucleosomes, which contain DNA and histones, are released into the circulation from damaged cells and can promote inflammation. We studied whether the on-admission levels of circulating nucleosomes predict the development of severe acute pancreatitis (AP), in particular among the patients who present without clinical signs of organ dysfunction. METHODS: This is a prospective study of 74 AP patients admitted to Helsinki University Hospital from 2003 to 2007. Twenty-three patients had mild, 27 moderately severe, and 24 severe AP as defined by the revised Atlanta criteria. 14/24 severe AP patients had no sign of organ dysfunction on admission (modified marshall score <2). Blood samples were obtained on admission and the plasma levels of nucleosomes were measured using enzyme-linked immunosorbent assay. RESULTS: The on-admission levels of nucleosomes were significantly higher in severe AP than in mild or moderately severe AP (p < 0.001 for all), higher in non-survivors (n = 8) than in survivors (p = 0.019), and correlated with the on-admission levels of C-reactive protein (p < 0.001) and creatinine (p < 0.001). Among the AP patients who presented without organ dysfunction, the on-admission nucleosome level was an independent predictor of severe AP (p = 0.038, gender-adjusted forward-stepping logistic regression). CONCLUSIONS: Circulating nucleosome levels may be helpful in identifying, on admission to hospital, the AP patients who present without clinical signs of organ dysfunction, and, yet, are bound to develop organ dysfunction during hospitalization. PMID- 26893909 TI - Light enhanced bone regeneration in an athymic nude mouse implanted with mesenchymal stem cells embedded in PLGA microspheres. AB - BACKGROUND: Biodegradable microspheres fabricated from poly (Lactic-co-glycolic acid) (PLGA) have attracted considerable attention in the bone tissue regeneration field. In this study, rabbit mesenchymal stem cells (rMSCs) adherent to PLGA microspheres were implanted into athymic nude mice and irradiated with 647 nm red light to promote bone formation. It was found that irradiating rMSCs with high levels of red light (647 nm) from an LED (light-emitting diode) increased levels of bone specific markers in rMSCs embedded on PLGA microspheres. RESULT: These increased expressions were observed by RT-PCR, real time-QPCR, immunohistochemistry (IHC), and von Kossa and Alizarin red S staining. Microsphere matrices coated with rMSCs were injected into athymic nude mice and irradiated with red light for 60 seconds showed significantly greater bone specific phenotypes after 4 weeks in vivo. CONCLUSION: The devised PLGA microsphere matrix containing rMSCs and irradiation with red light at 647 nm process shows promise as a means of coating implantable biomedical devices to improve their biocompatibilities and in vivo performances. PMID- 26893910 TI - Resistant hypertension caused by stenosis of the aorta in elderly women: three case reports. AB - Arterial hypertension is the most common cardiovascular disease in older than middle-aged patients. Reported incidence of secondary hypertension in this age group is around 10%. To evaluate secondary hypertension, history taking and physical examination should be precise, which are usually not routinely performed in busy outpatient clinic. Here, we report three cases of elderly women who are taking antihypertensive and visited outpatient clinic for uncontrolled hypertension. Their diagnosis of aortic stenosis was delayed, and its presence was suggested by detection of high abdominal aortic flow velocity during transthoracic echocardiography. This case report gives us lessons that suspicion of secondary hypertension and careful physical examination are most important to make diagnosis early. PMID- 26893908 TI - The EPIICAL project: an emerging global collaboration to investigate immunotherapeutic strategies in HIV-infected children. AB - The EPIICAL (Early-treated Perinatally HIV-infected Individuals: Improving Children's Actual Life with Novel Immunotherapeutic Strategies) project arises from the firm belief that perinatally infected children treated with suppressive antiretroviral therapy (ART) from early infancy represent the optimal population model in which to study novel immunotherapeutic strategies aimed at achieving ART free remission. This is because HIV-infected infants treated within 2-3 months of life have a much reduced viral reservoir size, and rarely show HIV-specific immunity but preserve normal immune development. The goal of EPIICAL is the establishment of an international collaboration to develop a predictive platform using this model to select promising HIV therapeutic vaccine candidates, leading to prioritisation or deprioritisation of novel immunotherapeutic strategies. To establish this platform, the EPIICAL Consortium aims to: develop predictive models of virological and immunological dynamics associated with response to early ART and to treatment interruption using available data from existing cohorts/studies of early-treated perinatally HIV-infected children; optimise methodologies to better characterise immunological, virological and genomic correlates/profiles associated with viral control; test novel immunotherapeutic strategies using in vivo proof-of-concept (PoC) studies with the aim of inducing virological, immunological and transcriptomic correlates/profiles equivalent to those defined by the predictive model. This approach will strengthen the capacity for discovery, development and initial testing of new therapeutic vaccine strategies through the integrated efforts of leading international scientific groups, with the aim of improving the health of HIV-infected individuals. PMID- 26893912 TI - Clinical hypertension: a new era. AB - We are delighted to announce the launch of the new journal Clinical Hypertension. Clinical Hypertension is an open-access, peer-reviewed, online journal, which will publish scientific investigation of the highest quality in the field of blood pressure regulation and pathophysiology, treatment, and prevention of hypertension. The editors encourage the submission of original articles that deal with basic, clinical, and population studies of hypertension and related fields, such as cardiology, nephrology, endocrinology, neuroscience, vascular biology, physiology, pharmacology, cellular and molecular biology, and genetics. PMID- 26893911 TI - Depressor action and vasorelaxation of methylene chloride fraction extracted from Rubus coreanum. AB - INTRODUCTION: The present study was designed to examine whether methylene chloride (CH2Cl2) fraction extracted from Rubus coreanum affects the contractility of the isolated thoracic aortic strips and blood pressure of normotensive rats. METHODS: One of the common carotid arteries or of the femoral arteries was catheterized with a polyethylene tubing. The tubing was connected to a pressure transducer, and pulse of the mean arterial blood pressure was recorded on a biological polygraph continuously. RESULTS: The CH2Cl2 fraction (range, 200 to 800 MUg/mL) significantly depressed both phenylephrine (PE, 10 MUM)- and high K(+) (56 mM)-induced contractile responses of the isolated thoracic aortic strips in a concentration-dependent fashion. In the simultaneous presence of N(omega) nitro-L-arginine methyl ester hydrochloride (L-NAME) (an inhibitor of nitric oxide [NO] synthase, 300 MUM) and the CH2Cl2 fraction (400 MUg/mL), both PE- and high K(+)-induced contractile responses were recovered to the significant level of the corresponding control response in comparison with inhibition of CH2Cl2 fraction treatment alone. Moreover, in the simultaneous presence of the CH2Cl2 fraction after pretreatment with 0.4% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane sulfonate), both PE- and high K(+)-induced contractile responses were recovered to the significant level of the corresponding control response compared to the inhibitory response of CH2Cl2 fraction treatment alone. Also, in anesthetized rats, the CH2Cl2 fraction (range, 0.3 to 3.0 mg/kg) injected into a femoral vein dose-dependently produced depressor responses. This hypotensive action of the CH2Cl2 fraction was greatly inhibited after treatment with phentolamine (1 mg/kg), chlorisondamine (1 mg/kg), L-NAME (3 mg/kg/30 min), or sodium nitroprusside (30 MUg/kg/30 min). Intravenous infusion of the CH2Cl2 fraction (range, 1.0 to 10.0 mg/kg/30 min) markedly inhibited norepinephrine induced pressor responses. DISCUSSION: Taken together, these results demonstrate that the CH2Cl2 fraction causes vascular relaxation in the isolated rat thoracic aortic strips as well as hypotensive action in anesthetized rats. These vasorelaxation and hypotension of the CH2Cl2 fraction seem to be mediated at least by the increased NO production through the activation of NO synthase of the vascular endothelium and the inhibitory adrenergic modulation. PMID- 26893914 TI - Spontaneous rupture of a renal artery pseudoaneurysm in a previously hypertensive patient. AB - Previously, renal artery pseudoaneurysms were thought to be extremely uncommon. However, these lesions are now being detected more frequently as incidental findings on computed tomography, magnetic resonance imaging, and the extensive use of angiography. The incidence of ruptured renal artery pseudoaneurysms is very low. We report a case of a giant renal artery pseudoaneurysm (9.4-cm diameter) with severe left flank pain and a syncopal attack in a young woman who did not control high blood pressure for a couple of years. PMID- 26893913 TI - Wall shear stress in hypertensive patients is associated with carotid vascular deformation assessed by speckle tracking strain imaging. AB - INTRODUCTION: Wall shear stress (WSS) is critically important in both vascular remodeling and atherosclerosis. Carotid intima-media thickness (IMT) and deformation parameters have been used as relevant indicators of carotid atherosclerosis. This study aimed to investigate the relationships between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. METHODS: Carotid artery ultrasound was performed in 100 untreated hypertensive patients. Morphologic and hemodynamic parameters of the CCA, including peak and mean WSS, global circumferential strain, peak posterior radial strain assessed by two dimensional speckle tracking method, and IMT, were measured. RESULTS: In patients with hypertension, there were significant correlations between carotid strain parameters and peak/mean WSS. Stepwise multiple regression analysis for carotid strain parameters after adjustment for age, carotid IMT, and brachial pulse wave velocity showed that peak WSS was an independent determinant of peak posterior radial strain (p = 0.009) and global circumferential strain (p = 0.002). CONCLUSIONS: These findings indicate that local shear stress is associated with carotid vascular deformation, which could be an underlying mechanism for the progression of atherosclerosis. PMID- 26893915 TI - 2013 Korean Society of Hypertension guidelines for the management of hypertension: part I-epidemiology and diagnosis of hypertension. AB - The standardized techniques of blood pressure measurement in the clinic are emphasized and the indications for ambulatory and/or home blood pressure monitoring are specified more broadly. The epidemiologic findings specific to Korean population related to blood pressure are reviewed. Cardiovascular risk of hypertensive patients are stratified based upon the data of a Korean population cohort study. PMID- 26893918 TI - Increased pulse wave velocity and augmentation index after isometric handgrip exercise in patients with coronary artery disease. AB - BACKGROUND: Arterial stiffness of patients with coronary artery disease (CAD), which is expected to be increased due to a generalized atherosclerotic process of human body, may be more evident after the acute increase of blood pressure (BP) or peripheral vascular resistance. Isometric handgrip exercise is a simple and easily applicable method to achieve this goal. We investigated the changes of hemodynamic parameters and arterial stiffness indexes after handgrip exercise in patients with CAD. METHODS: Forty-two subjects, who underwent coronary angiography (CAG), were enrolled. After CAG, baseline arterial waveforms were traced at the aortic root and external iliac artery using right coronary catheters. Arterial waveforms were recorded at 1, 2, and 3 min in the aortic root and at 3 min in the external iliac artery after isometric handgrip exercise at 30% ~ 40% of the maximal handgrip power. Augmentation pressure (AP) and augmentation index (AIx) were measured at aortic pressure waveforms. Pulse wave velocity (PWV) was calculated using the ECG-gated time difference of the upstroke of arterial waveforms and the distance between the aortic root and the external iliac artery. RESULTS: Thirty patients had CAD (CAD group), and others showed no significant coronary stenosis (non-CAD group). Baseline hemodynamic parameters including AIx and PWV were not different between both groups. After isometric handgrip exercise, central systolic blood pressure (BP), central diastolic BP, central pulse pressure, peripheral systolic BP, and peripheral pulse pressure were increased in all patients. AIx inclined significantly from 1 min after exercise only in patients with CAD (before 17.7% +/- 9.7% vs. 3 min after exercise 22.3% +/- 10.7%, p < 0.001). PWV also increased significantly after exercise only in patients with CAD (before 10.03 +/- 1.99 m/s vs. 3 min after 11.09 +/- 2.45 m/s, p < 0.001). CONCLUSIONS: Arterial stiffness indexes at rest were not different between patients with and without CAD. After isometric handgrip exercise, increased arterial stiffness became evident only in patients with CAD. PMID- 26893919 TI - Diurnal variation of flow-mediated dilatation in healthy humans. AB - INTRODUCTION: The measurement of flow-mediated dilatation (FMD) via ultrasound has been established as a reliable non-invasive measurement of endothelial function. However, the guidelines mention nothing regarding diurnal variation of FMD. Thus, we investigated the FMD in healthy people and diurnal variation of FMD. METHODS: Twenty-five apparently healthy persons participated in this study. All participants had no history of cardiovascular diseases, hypertension, or diabetes and used any medication. For each volunteer, the measurements were repeated in the morning and afternoon on two different days. We checked capillary blood glucose, total cholesterol, triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)-cholesterol. RESULTS: The average of FMD measurements was 8.45% +/- 2.39%. The mean values of systolic and diastolic blood pressure, heart rate, lipid profiles, and glucose levels were similar between the morning and afternoon measurements after 9-h fasting. There was no significant difference of FMD measurements between the morning and afternoon (8.32% +/- 2.27% and 8.58% +/- 2.56%, p = 0.329). Moreover, there was significant correlation between FMD in the morning and afternoon (r = 0.856, p < 0.001). CONCLUSIONS: Our study shows measurement of FMD was 8.45% in healthy Koreans. Also, there was no significant difference of FMD measurements between the morning and afternoon. PMID- 26893920 TI - The relationship between hypertension and sleep duration: an analysis of the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-3). AB - INTRODUCTION: Hypertension is a significant risk factor for cardiovascular disease (CVD). The majority of patients, however, cannot easily maintain a healthy blood pressure. Therefore, lifestyle modifications are important and may include getting enough sleep. The purpose of this study was to determine the relationship between sleep duration and hypertension, as defined by the Joint National Committee (JNC) 7 and JNC 8 guidelines. METHODS: We used the data from 6,365 individuals aged >= 18 years based on national data from a representative sample of the 5(th) Korea National Health and Nutrition Examination Survey V-3 in 2012. The participants were divided into three categories: JNC 7, JNC 8, and newly excluded only. The duration of sleep was classified as less than 5, 6, 7, 8, or more than 9 hours. RESULTS: Compared with the appropriate sleep duration of 7 hours, with a sleep duration of less than 5 hours, the recommended pharmacological treatment of hypertension rate increased 1.908-fold (95% CI = 1.483-2.456) according to the JNC 8 guidelines and 1.864-fold (95% CI = 1.446 2.403) according to the JNC 7 guidelines. However, there was no statistical difference with the other sleep categories. DISCUSSION: The recommended hypertension treatment rate increased significantly in the less than 5 hours sleep group according to the JNC 8 guidelines. To manage hypertension effectively, it may be useful to maintain a lifestyle of sleeping more than 6 hours. PMID- 26893916 TI - 2013 Korean Society of Hypertension guidelines for the management of hypertension. Part II-treatments of hypertension. AB - Treatment strategies are provided in accordance with the level of global cardiovascular risk, from lifestyle modification in the lower risk group to more comprehensive treatment in the higher risk group. Considering the common trend of combination drug regimen, the choice of the first drug is suggested more liberally according to the physician's discretion. PMID- 26893922 TI - The approach of general practitioners in Lagos to the detection and evaluation of hypertension. AB - INTRODUCTION: Hypertension (HTN) control is a major public health and clinical challenge. A number of guidelines exist globally to assist in tackling this challenge. The aim of this study was to determine conformity of the HTN detection and evaluation practices of a sample of Lagos-based general practitioners (GPs) to international guidelines. METHODS: Self-administered structured questionnaires were used to collect data from a cohort of GPs attending continuing medical education programs in Lagos. RESULTS: Out of the 460 GPs that were approached, 435 agreed to participate in the study, with questionnaires from 403 GPs analyzed. The average age and number of years post-registration of the GPs were 40.0 +/- 11.3 years and 14.3 +/- 11.1 years, respectively. Two thirds (n = 269) were in private practice. Their daily average total and HTN patients' loads were 17.4 +/- 14.3 and 4.4 +/- 3.5, respectively. Awareness of HTN guidelines was 46.7% (n = 188), while 18.1% (n = 73) was able to name one or more HTN guidelines. The approaches of these GPs to the detection and evaluation of HTN and their relationships to the GPs' experience were heterogeneous. DISCUSSION: The approach of the GPs to detection and evaluation of HTN though heterogeneous is unsatisfactory and may partly contribute to poor HTN control in Nigeria. Strengthening the capacity of GPs in this regard through continuous medical education may greatly improve HTN control. PMID- 26893917 TI - 2013 Korean Society of Hypertension guidelines for the management of hypertension: part III-hypertension in special situations. AB - Different treatment strategies are suggested for special situations. Hypertension is common in the elderly and frequently accompanied by or complicates other clinical conditions such as metabolic syndrome, coronary artery disease, heart failure, stroke, diabetes mellitus and chronic kidney disease. PMID- 26893921 TI - Role of echocardiography in clinical hypertension. AB - Hypertension is a major and correctable cardiovascular risk factor. The correct diagnosis of hypertension and precise assessment of cardiovascular risk are essential to give proper treatment in patients with hypertension. Although echocardiography is the second-line study in the evaluation of hypertensive patients, it gives many clues suggesting bad prognosis associated with hypertension, including increased left ventricular (LV) mass, decreased LV systolic function, impaired LV diastolic function, and increased left atrial size and decreased function. Along with conventional echocardiographic methods, tissue Doppler imaging, three-dimensional echocardiography, and strain echocardiography are newer echocardiographic modalities in the evaluation of hypertensive patients in the current echocardiographic laboratories. Understanding conventional and newer echocardiographic parameters is important in the diagnosis and assessment of cardiovascular risk in hypertensive patients. PMID- 26893924 TI - Relationship between uric acid and blood pressure in different age groups. AB - INTRODUCTION: Serum uric acid (UA) has been known to have a positive association with blood pressure (BP). However, the relationship between serum UA and BP in different age groups is unclear. METHODS: A total of 45,098 Koreans who underwent health examinations at Korea Association of Health Promotion with no history of taking drugs related with UA and/or BP were analyzed for determining the relationship between serum UA and BP. RESULTS: In men <40, serum UA was significantly associated with systolic (beta = 0.25, p = 0.002) and diastolic BP (beta = 0.41, p < 0.001) after adjustment for age, diabetes, dyslipidemia, body mass index, and estimated glomerular filtration rate. Men between ages 40 and 59 showed similar results regarding diastolic BP. The association between serum UA and BP was stronger in women <40 (beta = 0.54, p < 0.001 for systolic BP; beta = 0.65, p < 0.001 for diastolic BP) and in between 40 and 59 (beta = 0.51, p < 0.001 for diastolic BP). The association was not significant in men and women >=60. The odds ratios (ORs) of hyperuricemia for hypertension were 1.25 (95% confidence interval [CI], 1.08 to 1.45; p = 0.003) and 1.33 (95% CI, 1.11 to 1.60; p = 0.002) in men <40 and in between 40 and 59, respectively, in the multivariate analysis. The OR was 2.60 (95% CI, 1.37 to 4.94; p = 0.0034) in women <40. The relationship between hyperuricemia and hypertension was not significant in other age/gender groups. DISCUSSION: In contrast to the elderly of 60 and over, the non-elderly showed significant associations between serum UA and BP. PMID- 26893925 TI - Carotid intima-media thickness is not related with clinical outcomes in young hypertensives. AB - INTRODUCTION: Careful observations of long- and short-term outcomes associated with carotid intima-media thickness (IMT) are relatively limited. METHODS: A total of 2,972 patients (male:female = 1,960:1,012; mean age = 62 +/- 12 years) who underwent carotid IMT measurements from September 2003 to March 2009 were divided into four groups. Group I (n = 271; mean age, 42 +/- 7.8 years) included normotensive younger subjects (males, <45 years and females <55 years), group II (n = 992; mean age, 63 +/- 9 years) included normotensive elderly subjects, group III (n = 177; mean age, 46 +/- 7.8 years) was hypertensive younger subjects, and group IV (n = 1,532; mean age, 63 +/- 10.2 years) was hypertensive elderly subjects. We analyzed the clinical and cardiovascular events in the younger hypertensive subjects based on IMT measurements. RESULTS: The baseline characteristics of the subjects showed that carotid IMT increased in the elderly subjects and in patients with hypertension. Poor clinical outcomes, such as all cause death and major adverse cardiac events, were related with age, not with hypertension. Among the conventional risk factors, age and the highest quartile level of right maximum carotid IMT were related with major adverse events (young: odds ratio [OR], 0.47; 95% confidence interval [CI], 0.25 to 0.9 vs. OR, 1.73; 95% CI, 1.20 to 2.49). The patients in the highest quartile of carotid IMT had worse survival outcomes than those with the lowest IMT (p = 0.03). DISCUSSION: Subjects with hypertension had increased carotid IMT levels. Controlling hypertension and carefully evaluating carotid IMT are important to prevent cardiovascular events even in younger subjects with hypertension. PMID- 26893923 TI - Angiotensin II induces endoplasmic reticulum stress in podocyte, which would be further augmented by PI3-kinase inhibition. AB - INTRODUCTION: Angiotensin II (Ang II) contributes to the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. On renal effects, Ang II plays an important role in the development of proteinuria and glomerulosclerosis by the modification of podocyte molecules and cell survival. In the present study, we investigated the effect of Ang II on endoplasmic reticulum (ER) stress in podocytes. METHODS: We cultured mouse podocytes with increasing doses of Ang II and evaluated ER stress markers by Western blotting. RESULTS: Ang II increased Bip protein, an ER chaperone, in a dose-dependent manner at 24 h, which was ameliorated by losartan, an angiotensin II type 1 receptor antagonist. Ang II also increased ER stress markers, such as phospho-PERK, phospho-eIF2alpha, and ATF4 proteins of podocyte, significantly in a dose-dependent manner at 24 h. Increased phospho-PERK and ATF4 proteins were further augmented by phosphoinositide 3 (PI3)-kinase inhibitor, LY294002, which suggested that Ang II could induce podocyte ER stress of PERK-eIF2alpha-ATF4 axis via PI3-kinase pathway. DISCUSSION: These studies suggest that Ang II could induce podocyte ER stress of PERK-eIF2alpha-ATF4 axis via PI3-kinase pathway, which would contribute to the development of podocyte injury induced by Ang II, and the augmentation of PI3-kinase would be a therapeutic target. PMID- 26893926 TI - Casual blood pressure of adolescents attending public secondary schools in Maiduguri, Nigeria. AB - INTRODUCTION: Although evidence exists that adolescents' hypertension could lead to adults' hypertension, it is a general belief that measures for early detection and treatment of this condition is seldom undertaken especially in medically underserved communities such as Maiduguri, Northeastern Nigeria. This study investigated the prevalence of undiagnosed hypertension among adolescents in Maiduguri, Nigeria, and explored the association between undiagnosed hypertension and adolescents' physical characteristics and parental socio-demographic factors. METHODS: Participants' physical characteristics were assessed, and information on their socio-demographics including parental socioeconomic status were obtained. Blood pressures and heart rates of the participants were also measured three times at 5-10-min period. RESULTS: The prevalence of undiagnosed hypertension among the students was 13.2 %, and overwhelming majority (82.4 %) of the hypertensive students were in the prehypertensive stage, while 17.6 % were in the stage 1 classification of hypertension. Higher prevalence of undiagnosed hypertension was observed for the females compared to the male adolescents (X (2) = 15.49, p = 0.001), and presence of undiagnosed hypertension is positively but tenuously linked to age (r = 0.11, p = 0.01), body mass index (r = 0.10, p = 0.01), and parental income (r = 0.26, p = 0.02) of the students. DISCUSSION: This study suggests that any effective programs designed to mitigate undiagnosed hypertension among adolescents in this city should include strategies that address possible barriers to physical activity and exercise among female adolescents in the society. PMID- 26893927 TI - Impaired deformability of circulating erythrocytes obtained from nondiabetic hypertensive patients: investigation by a nickel mesh filtration technique. AB - INTRODUCTION: Hypertension is associated with microcirculatory disturbance, and erythrocyte deformability is a major determinant of the microcirculation. However, impairment of erythrocyte deformability in hypertensive patients in relation to antihypertensive treatment is unclear. The present study aimed to investigate this impairment in hypertensive patients under treatment using a highly sensitive and quantitative nickel mesh filtration technique. METHODS: Deformability was evaluated by filterability, defined as the flow rate of a hematocrit-adjusted erythrocyte suspension relative to that of saline under a specific filtration pressure in a pressure-flow curve obtained by continuous filtration. Baseline characteristics of hypertensive patients (n = 101) and age matched normotensive subjects (n = 14) were obtained from medical records, and diabetic patients were excluded. RESULTS: Erythrocyte deformability in the hypertensive group was significantly (p = 0.010) lower (87.8 +/- 2.2 %) than that of the normotensive group (89.4 +/- 1.7 %) and inversely proportional (r = 0.303, p = 0.002) to the mean blood pressure (BP) measured on blood sampling for the filtration study. Stepwise multiple regression analysis demonstrated that this impairment was mostly attributable to the mean BP (p = 0.001), whereas current smoking and episodes of stroke or coronary artery disease were not contributors. DISCUSSION: These findings indicate that erythrocyte deformability is impaired in the hypertensive patients, which depends on the current BP control rather than target organ damage. PMID- 26893928 TI - Clinical attributes, treatment, and control in hypertension (CATCH)-a French and Italian longitudinal patient database study. AB - INTRODUCTION: Hypertension, a risk factor for cardiovascular disease (CVD), is frequently associated with other CVD risk factors. Despite recent improvement in blood pressure (BP) control in Europe, a substantial proportion of patients fail to achieve BP targets. METHODS: This retrospective cohort study used longitudinal patient databases (LPDs) in France and Italy to examine CVD risk profiles, treatment patterns, and BP goal attainment in hypertensive patients treated in real-world clinical practice between 2007 and 2008. Overall, 147,964 and 140,189 eligible patients from LPDs in France and Italy, respectively, were prescribed an antihypertensive medication in 2007. RESULTS: Among patients with hypertension with other risk factors (France 88 %, Italy 83 %), the most prevalent risk factors were being elderly (France 66.9 %, Italy 70. 9 %), followed by hypertension combined with dyslipidemia (France 36.7 %, Italy 23.9 %) and isolated systolic hypertension (France 32.5 %, Italy 24.2 %). The odds ratios for target BP attainment were significantly (p < 0.001) higher in patients with hypertension without other risk factors vs patients with hypertension with other risk factors (1.41 [95 % confidence interval 1.35, 1.48] in France; 1.38 [1.31, 1.46] in Italy). The odds of BP control were significantly lower for patients with vs patients without an associated CVD risk factor (range 0.54 to 1.10 France; 0.59 to 1.17 Italy). DISCUSSION: This study demonstrates that the majority of treated hypertensive patients in France and Italy have at least one additional CVD risk factor. Despite treatment with antihypertensive medications, blood pressure attainment was substantially less optimal in patients with an associated CVD risk factor compared to patients without an associated CVD risk factor. PMID- 26893929 TI - A psychosocial perspective of medication side effects, experiences, coping approaches and implications for adherence in hypertension management. AB - INTRODUCTION: This study examined whether psychosocial variables influenced patients' perception and experience of side effects of their medicines, how they coped with these experiences and the impact on medication adherence behaviour. METHODS: A hospital-based mixed methods study using quantitative and qualitative approaches was conducted with hypertensive patients. Participants were asked about side effects, medication adherence, common psychological symptoms and coping mechanisms with the aid of standard questionnaires and an interview guide. RESULTS: The experiences of side effects-such as palpitations, frequent urination, recurrent bouts of hunger, erectile dysfunction, dizziness, cough, physical exhaustion-were categorized as no/low (39.75 %), moderate (53.0 %) and high (7.25 %). Significant relationships between depression (x (2) = 24.21, p < 0.0001), anxiety (x (2) = 42.33, p < 0.0001), stress (x (2) = 39.73, p < 0.0001) and side effects were observed. A logistic regression model using the adjusted results for this association is reported-depression [OR = 1.9 (1.03-3.57), p = 0.04], anxiety [OR = 1.5 (1.22-1.77), p <= 0.001] and stress [OR = 1.3 (1.02 1.71), p = 0.04]. Side effects significantly increased the probability of individuals to be non-adherent [OR = 4.84 (95 % CI 1.07-1.85), p = 0.04] with social factors, media influences and attitudes of primary care givers further explaining this relationship. Personal adoption of medication modifying strategies, espousing the use of complementary and alternative treatments and interventions made by clinicians were the main forms of coping with side effects. DISCUSSION: Results from this study show that, in addition to a biomedical approach, the experience of side effects has biological, social and psychological interrelations. The results offer more support for the need for a multi disciplinary approach to healthcare where all forms of expertise are incorporated into health provision and patient care. PMID- 26893930 TI - Hypertensive emergencies: a new clinical approach. AB - The expression 'hypertensive urgencies' includes many diseases. The unifying features of these diseases are a high level of arterial pressure and acute distress of one or more organs. The aim of the review was to define the idea of the 'acute hypertension' as a new concept, different from 'chronic hypertension'. Acute hypertension might be related to 'organ damage' because it is the cause, the consequence or an effect of the acute stress. We compounded a narrative review which has included analyses of 373 articles. The structure of the search strategy included a literature search of PubMed, MEDLINE, Cochrane Library and Google Scholar databases. We applied the following inclusion criteria: prospective double-blind randomised controlled trials, experimental animal work studies, case-control studies and recruiting patients representative of the general sick population. In this review, the diseases included in the term 'hypertensive emergencies' share 'acute' hypertension. This is a new idea that emphasises the suddenly increased arterial pressure, irrespective of the initial arterial pressure and independent of the goals of hypertension control. The 'hypertensive emergencies' have been grouped together in three subsets: (1) diseases that result from acute hypertension that is caused by faulty regulation of the peripheral circulation (acute primary hypertension), (2) diseases that produce hypertension (acute secondary hypertension) and 3) diseases that have hypertension as an effect of the acute stress caused by the principle disease (acute associated hypertension). This review highlights a novel idea: acute hypertension is a common sign of different diseases characterised by the sudden surge of arterial pressure, so overwhelming the difference between hypertensive emergencies and urgencies. The judgment of acute hypertension is independent of the initial arterial pressure, normotension or hypertension and is linked with the transient failure of the baroreflex. Hypertensive emergencies are grouped together because all of these diseases require prompt therapy to prevent the negative outcomes of acute hypertension. PMID- 26893931 TI - Left ventricular hypertrophy and diastolic function in children and adolescents with essential hypertension. AB - INTRODUCTION: Left ventricular hypertrophy and diastolic dysfunction in children and adolescents with essential hypertension tend to be underdiagnosed. The aims of this study were to investigate left ventricular hypertrophy and diastolic dysfunction in the subjects with essential hypertension defined by ambulatory blood pressure monitoring. METHODS: A total of 38 Korean subjects aged 9-19 years without secondary causes of hypertension were reviewed. Ambulatory blood pressure monitoring was done in the 38 subjects to diagnose hypertension and gain the information of blood pressure pattern. The subjects were divided into two groups: a group with elevated blood pressure (BP) index (n = 29) and a group with normal BP index (n = 9). Two-dimensional ultrasound with M-mode imaging and tissue Doppler imaging were performed to measure left ventricular mass index and to assess the left ventricular diastolic dysfunction. RESULTS: Left ventricular mass index(g/m(2.7)) was significantly higher in the group with elevated BP index than the group with normal BP index, but there were no differences in left ventricular diastolic dysfunction evaluated by E/A ratio and E/E' ratio. Left ventricular mass index was related only with body mass index, while any of the ambulatory blood pressure monitoring parameters did not predict left ventricular hypertrophy. In terms of diastolic dysfunction in essential hypertension, E/E' ratio in the subjects with left ventricular hypertrophy was higher than that in the other subjects without left ventricular hypertrophy. DISCUSSION: Left ventricular mass index is significantly correlated with body mass index in children and adolescents with essential hypertension, and the diastolic dysfunction could be in higher risk in subjects with left ventricular hypertrophy. PMID- 26893932 TI - Change in fatty liver status and 5-year risk of incident metabolic syndrome: a retrospective cohort study. AB - INTRODUCTION: Fatty liver is associated with metabolic syndrome (MetS) but it may also occur without MetS. Whether resolution of fatty liver in the general population affects risk of MetS is unknown. Our aim was to determine whether a change in fatty liver status (either the development of new fatty liver or the resolution of existing fatty liver) would modify the risk of de novo MetS. METHODS: Two thousand eighty-nine people without hypertension, diabetes, and MetS were examined at baseline and at 5-year follow-up using a retrospective cohort study design. Fatty liver status was assessed at baseline and at follow-up by ultrasonography. Adjusted hazard ratios (aHR) and 95 % confidence intervals (CIs) for de novo MetS at follow-up were calculated controlling for the potential confounders, compared to the reference group (people who never had fatty liver at baseline and follow-up). RESULTS: During follow-up, fatty liver developed in 251 people and fatty liver resolved in 112 people. After the adjustment for multiple confounders, persisting fatty liver and incident fatty liver development were associated with de novo MetS, with aHR of 2.60 (95 % CIs [1.61,4.20]) and 3.31 (95 % CIs [1.99,5.51]), respectively. Risk of new MetS in resolved fatty liver group was attenuated with insignificant aHR of 1.29 accompanying 95 % CIs of 0.60 and 2.80. DISCUSSION: Development or maintenance of fatty liver is positively associated with occurrence of new MetS. Resolution of fatty liver status has similar risk of de novo MetS with those who never had fatty liver. Therefore, cautious management is needed with those with fatty liver. PMID- 26893933 TI - The relationship between left ventricular mass index and body composition in new diagnosed hypertensive patients. AB - BACKGROUND: Cardiovascular disease (CVD) is considered a public health burden and most common cause of mortality in all over the world. The latency time for developing CVD may be several decades. the objective of this study was to examine the relationship between body composition and Left Ventriculare Mass Index (LVMI) in newly diognosed hypertensive patients. METHODS: We enrolled 120 new-diagnosed hypertensive patients (mean age 45 +/- 8 years) who admitted to our nephrology clinic. Body fat percentage (BFP) was measured by bioelectrical impedance (BIA). Echocardiography examinations were performed for all patients. RESULTS: Mean values of Waist hip ratio, Body mass index, Body fat percentage, Systolic blood pressure, Diastolic blood pressure were significantly higher for females than males (all p values <0.05). The female patients had higher LVMI than male patients (94.8 +/- 13.1 vs 89.2 +/- 14.6, p < 0.05). The study patients were divided into 3 groups according to their BFP defined by BIA. Group 3 patients, who exhibited higher body fat, had significantly higher BMI (p < 0,05), total leukocyte count (p < 0.05), CRP (p < 0.05), triglyceride (p < 0.05), and female predominance. Group 3 patients were statistically older than group 1 patients (46.2 vs. 40.6 years, p < 0.05). Additionally, LVMI levels were higher in Group 3 than Group 1 (p < 0.05) (Table 3). In logistic regression analysis, independent factors affecting LVMI were age, weight, gender and BFP (all p values were <0.05). CONCLUSIONS: BFP was associated with higher LVMI, in newly diognosed hypertensive patients. Its use results in significantly lower proportions of individuals with LVH in the population, in particular among hypertensive and the obese patients. PMID- 26893934 TI - Association among epicardial fat, heart rate recovery and circadian blood pressure variability in patients with hypertension. AB - BACKGROUND: Epicardial fat tissue is known to have an unique endocrine function which affect the cardiac autonomic system. Heart rate recovery (HRR) is a simple non-invasive measurement that assesses autonomic nervous system dysfunction. We aimed to investigate the association among epicardial fat thickness (EFT), HRR and circadian blood pressure (BP) variation in patients with hypertension. METHODS: A total of 358 consecutive patients who underwent both 24-hour ambulatory BP monitoring (ABPM) and a treadmill test were enrolled. Echocardiographic EFT and HRR, defined as peak heart rate minus heart rate after a 1-min recovery time, were measured. Patients were classified according to the ABPM; 147 patients with hypertension with a dipping pattern at night (dippers), 140 patients with hypertension with a non-dipping pattern at night (non-dippers) and 71 normotensive controls. RESULTS: EFT was significantly higher in hypertensive patients, especially in the non-dipper group, compared to the controls (non-dippers, 7.5 +/- 2.9 mm; dippers, 6.6 +/- 1.6 mm; controls, 5.5 +/- 2.1 mm; p < 0.001). HRR was significantly lower in both hypertensive groups as compared to the control group and was the lowest in the non-dipper group (non dipper, 26.6 +/- 18.6; dipper, 29.5 +/- 21.5; control, 71.4 +/- 19.8; p < 0.001). EFT was significantly correlated with age, body mass index, 24-hour mean systolic BP and 24 h mean BP variability, whereas exercise duration, metabolic equivalents (METs) and HRR were inversely correlated with EFT. Furthermore, EFT > 6.7 mm was associated with a blunted HRR with 76 % sensitivity and 61 % specificity (ROC area under curve: 0.71, 95 % confidence interval, CI = 0.65-0.76, p < 0.001). In a multivariate analysis, EFT (odds ratio, OR = 3.53, 95 % CI = 1.20-10.37, p = 0.022) and 24-hour mean BP variability (OR = 1.09, 95 % CI = 1.03-1.16, p = 0.005) were independent predictors of a blunted HRR defined as HRR <= 12 beats (n = 63) in patients with hypertension. CONCLUSION: EFT and HRR were significantly correlated with circadian BP variability in patients with hypertension. EFT and circadian BP variability were independent predictors of blunted HRR, which suggests a link between epicardial fat and autonomic dysregulation in hypertension. PMID- 26893935 TI - Non-invasive assessment of vascular alteration using ultrasound. AB - It is well known that arterial function relates to cardiovascular morbidity and mortality. The noninvasive technology for the assessment of arterial function has developed as the importance of prevention of early cardiovascular disease has been emphasized. Over 2-D and Doppler echocardiography, speckle-tracking echocardiography has emerged as a valuable ultrasound imaging technique that allows for an objective and quantitative evaluation of global and regional myocardial function. Recently, several studies have extended its applicability beyond cardiac chambers, such as artery. Measurement of carotid arterial strain with speckle tracking ultrasound has been shown to be feasible and reliable. This review describes the new ultrasound techniques to assess arterial function and their clinical implications. PMID- 26893937 TI - Mesoglycan attenuates VSMC proliferation through activation of AMP-activated protein kinase and mTOR. AB - BACKGROUND: Vascular smooth muscle cells (VSMC) proliferation contributes significantly to intimal thickening in atherosclerosis and restenosis diseases. Platelet derived growth factor (PDGF) has been implicated in VSMC proliferation though the activation of multiple growth-promoting signals. Mesoglycan, a natural glycosaminoglycans preparation, is reported to show vascular protective effect. However, the mechanisms by which mesoglycan inhibits proliferation of VSMC are not fully understood. Here, we investigated whether mesoglycan exert therapeutic effect via AMP-activated protein kinase (AMPK) and its underlying mechanism. METHODS: We cultured VSMC with increasing doses of mesoglycan. AMPK activation was measured by western blot analysis and cell proliferation was measured by flow cytometry. RESULTS: Mesoglycan dose- and time- dependently increased the phosphorylation of AMPK (Thr(172)) and its upstream target, LKB1 (Ser(428)) and its downstream, ACC (Ser(79)) in VSMCs. Mesoglycan also blocked the PDGF stimulated cell cycle progression through the G0/G1 arrest. AMPK DNalpha1, AMPK DNalpha2 or AMPK siRNA reduced the mesoglycan-mediated inhibition of VSMC proliferation. AMPK signaling activated by mesoglycan regulates mTOR phosphorylation which closely related to cell proliferation. CONCLUSION: These data suggest that mesoglycan-induced AMPK activation suppress the VSMC proliferation via mTOR-dependent mechanism and mesoglycan may have beneficial effects on vascular proliferative disorders such as atherosclerosis. PMID- 26893936 TI - The platelet-to-lymphocyte ratio reflects the severity of obstructive sleep apnea syndrome and concurrent hypertension. AB - BACKGROUND: Chronic intermittent hypoxia, platelet activation and inflammation all play roles in the pathogenesis of obstructive sleep apnea syndrome (OSAS), which may increase the risk of cardiovascular disease (CVD). The aim of this study was to evaluate the relationship of the platelet-to-lymphocyte ratio (PLR) as a new biomarker showing systemic inflammation and platelet distribution width (PDW) as an indicator of platelet activation to the severity of OSAS. METHODS: A total of 290 patients suspected with OSAS who underwent a full night of polysomnography were included. The patients were placed into 4 separate groups according to their apnea-hypopnea index (AHI) scores; the control group (AHI <5), mild OSAS group (AHI 5-15), moderate OSAS group (AHI 16-30), and severe OSAS group (AHI >30). CVD risk was defined by the presence of hypertension, diabetes mellitus, current smoking, and dyslipidemia. RESULTS: Higher AHI groups were significantly correlated with increasing age, body mass index, systolic blood pressure and male sex. PLR and PDW were also significantly associated with AHI (r = 0.417 for PLR and r = 0.227 for PDW, all p-values < 0.001) and the Epworth sleepiness scale (r = 0.160 for PLR and r = 0.189 for PDW, all p-values <0.05). Multivariate regression analysis revealed that AHI >=9.2 (adjusted odds ratios [OR] 5.03, 95 % confidential interval (CI) = 1.67-15.2, p = 0.004) and PLR >=159 (adjusted OR 2.81, 95 % CI = 1.34-5.91, p = 0.006) were independently associated with the presence of hypertension. CONCLUSION: PLR and PDW are associated with OSAS severity. PLR may also be useful as a systemic biomarker for the concurrent hypertension in OSAS patients. PMID- 26893938 TI - Prevalence and characteristics of resistant hypertension at primary clinics in Korea: a nationwide cross-sectional study. AB - BACKGROUND: Although resistant hypertension (RH) is known to be associated with higher rates of cardiovascular events than is non-RH, there are no reported data on the prevalence of RH in Korean patients. We evaluated the prevalence and characteristics of RH among hypertensive patients treated at primary clinics in Korea. METHODS: Between August 2010 and January 2011, 247 primary care physicians enrolled 3088 patients with essential hypertension. We acquired demographic and anthropometric data using a questionnaire, evaluated blood pressure, and conducted a variety of laboratory tests using serum and urine. RH was defined as systolic blood pressure >=140 mmHg or diastolic blood pressure >=90 mmHg with the use of three antihypertensive agents of different classes, including a diuretic, or controlled hypertension with the use of four or more medications. RESULTS: We analyzed 3088 patients with hypertension, 48.3 % of whom were men. The mean age of patients was 64.3 +/- 11.3 years and the prevalence of RH was 7.9 %. Patients with RH were more likely to be men, and to have higher waist circumference, increased blood levels of HbA1c, triglycerides, and serum creatinine, lower blood levels of high-density lipoprotein (HDL), and higher rates of current smoker, history of heart failure or coronary artery disease, and electrocardiographic left ventricular hypertrophy (LVH), than were patients with non-RH (all comparisons, P < 0.05). In the multivariate analysis, RH was shown to be significantly associated with the following conditions: presence of electrocardiographic LVH (odds ratio [OR] 2.23, 95 % confidence interval [CI] 1.34-3.71), current smoker (OR 1.75, 95 % CI 1.27-2.40), renal impairment (OR 1.65, 95 % CI 1.23-2.22), abdominal obesity (OR 1.60, 95 % CI 1.20-2.13), and cardiovascular diseases (OR 1.50, 95 % CI 1.04-2.17). CONCLUSIONS: The prevalence of RH was relatively low at primary clinics in Korea compared with the prevalence reported in other countries. RH was associated with electrocardiographically confirmed LVH, renal impairment, current smoker, abdominal obesity, and cardiovascular diseases. These are the first reported data of RH in Korea. Our findings may be helpful in the early detection and thorough clinical management of patients with RH at primary clinics. PMID- 26893939 TI - Lifestyle including dietary habits and changes in coronary artery calcium score: a retrospective cohort study. AB - BACKGROUND: General diet and lifestyle are considered to have an effect on levels of atherosclerosis but previous studies have shown inconsistent results. The aim of this study was to investigate whether macronutrient intake, physical activity and depressive symptoms are associated with progression of preclinical atherosclerosis in healthy Korean adults. METHODS: A total of 2623 individuals from Kangbuk Samsung Hospital Health Screening Center in South Korea were enrolled between 2010 and 2012 and had follow-up at 2013. Every participant received a non-enhanced coronary computed tomography (CT) and completed questionnaires for food intake frequency, depression and physical activity levels. The study population was divided into two groups according to CAC progression, namely CAC group (CAC score >0) or non-CAC group (CAC score <= 0), and were compared according to macronutrient intake, degree of depressive symptoms and physical activity. RESULTS: A total of 2175 subjects were eligible for the analysis and among them, 592 subjects had progression of CAC. Total energy, carbohydrate and fat intake showed significant differences between the two groups (p-values of 0.01, 0.021 and 0.016 respectively). However, levels of protein intake did not vary for the two groups (p = 0.286). Depressive symptoms and extent of physical activity were similar between the two groups. Multivariate analysis was conducted with adjustment for possible confounding factors. The hazard ratios for CAC progression were not different according to macronutrient intake, degree of depressive symptoms and physical activity. CONCLUSION: In this large relatively healthy population based observational study, CAC progression showed no significant association with total energy intake, proportion of macronutrient intake, depressive symptom and physical activity. PMID- 26893941 TI - Prevalence of resistant hypertension and associated factors for blood pressure control status with optimal medical therapy using Korean ambulatory blood pressure monitoring registry data. AB - BACKGROUND: Resistant hypertension (RH) may be one of the cause of the plateau in improving the control rate in hypertension (HT) management. The misdiagnosis of RH by clinic blood pressure (BP) is important clinical problem. Aim of the study were to investigate the prevalence of RH by ambulatory blood pressure monitoring (ABPM) and the factor associated with control status of ambulatory BPs. METHODS: For 1230 subjects taking one or more antihypertensive medication (AHM) enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) registry, the prevalence of RH was calculated which was defined as uncontrolled BP by three AHM classes including diuretic or BP in need of four or more AHM classes. The prevalence determined by clinic versus ambulatory BP was compared. RESULTS: The age was 59.3 +/- 12.5 years, and 44.3 % were female (n = 1230). Among them 72 subjects were taking three AHM drugs including diuretics and 105 subjects were taking four or more AHM classes. With uncontrolled daytime ambulatory BP in 41 among 72 subjects, prevalence of RH was 11.9 % (146/1230). By using nighttime BP criteria, there was significant difference in the prevalence of RH for clinic versus nighttime BP (146/177 vs. 159/177, p = 0.0124). For control status of daytime BP, masked uncontrolled BP was 16.9 % and controlled BP with white-coat effect was 14.1 %. For nighttime BP control status, odd ratios for smoking (0.624), drinking (1.512), coronary artery disease (0.604), calcium antagonist (1.705), and loop diuretics (0.454) were all significant. CONCLUSION: The prevalence itself was 11.9 % by daytime BP and it was significantly higher when using nighttime BP criteria. Control status of daytime BP was misclassified in 31.0 %. Smoking, drinking, coronary artery disease, calcium antagonist, and loop diuretics were associated with nighttime BP control status. PMID- 26893942 TI - The role of abnormal metabolic conditions on arterial stiffness in healthy subjects with no drug treatment. AB - BACKGROUND: Subjects with abnormal metabolic conditions had increased risk for cardiovascular disease. We investigated the role of abnormal metabolic conditions on arterial stiffness in healthy subjects with no drug treatment. METHODS: A total 601 subjects (age 48.7 +/- 11.8 years, male 46.2 %, hypertension 19.1 %) were enrolled. Major cardiovascular risk factors, metabolic conditions and parameters (pre-diabetes, diabetes mellitus, metabolic syndrome, fasting blood sugar (FBS), glycated hemoglobin), lipid profiles, hsCRP, and brachial ankle pulse wave velocity (baPWV) were measured. RESULTS: Subjects with metabolic syndrome (n = 200) had higher baPWV than in subjects without metabolic syndrome (n = 401) even after adjustments for age, sex and presence of hypertension (1435.9 +/- 212.2 vs. 1336.5 +/- 225.0 cm/sec, p < 0.001). The differences of baPWV among normal FBS, prediabetes and diabetes mellitus groups are significant (P for trend = 0.036) by multivariate analysis (adjustments for age, sex, office systolic blood pressure). Subjects with diabetes mellitus (n = 30) had higher baPWV than in subjects with normal FBS (n = 384, 1525 +/- 267.1 vs. 1341.5 +/- 224.1 cm/sec, P = 0.016 adjustments for age, sex, office systolic blood pressure). BaPWV in subjects with prediabetes (n = 187) was slightly higher, but not statistically significant than in subjects with normal FBS (P = 0.377). Of interest, FBS was one of the independent predictors for increased baPWV (beta = 0.809, 95 % CI 0.222-1.397, p = 0.007) by multivariate analysis. CONCLUSIONS: Subjects with abnormal metabolic conditions have increased arterial stiffness independent of age and BP which may contribute to the development of cardiovascular disease. PMID- 26893940 TI - Electrocardiogram derived QRS duration associations with elevated central aortic systolic pressure (CASP) in a rural Australian population. AB - BACKGROUND: Prolonged electrocardiogram QRS durations are often present in hypertensive patients. Small increases in QRS duration serve as independent risk factors for both increased cardiovascular and all-cause mortality. Aortic stiffness is associated with increases in central aortic systolic blood pressure (CASP). However CASP and ECG QRS duration interactions have not been established in rural community populations. Our aims are to determine if QRS duration > 100 msec is associated with an elevated CASP measure in an Australian rural population. METHODS: A retrospective cross sectional population was obtained from the CSU Diabetes Screening Research Initiative data base where 68 participants had both central aortic pressure recorded and ECG derived QRS duration. Central aortic pressure was determined by directly recording radial arterial tonometry and brachial cuff pressure (HealthStats, Singapore). Resting 12-lead electrocardiograms were obtained from each subject using a Welch Allyn PC-Based ECG system. RESULTS: The population had a mean CASP of 137.8 mmHg, higher than previously reported in other population studies. In 8/68 subjects with a prolonged cardiac QRS duration >120 msec, CASP ranged from 129 mmHg - 182 mmHg. When subgroup analysis was stratified on the basis QRS duration <100 msec and >=100 msec significant differences (p = 0.036) were observed for mean CASP, 130.6 mmHg +/- 15.6 (SD) versus 140.6 mmHg +/- 16.8 (SD), respectively. CONCLUSIONS: Our results suggest that an arbitrary CASP reading greater than a value 140 mmHg raises suspicion of a prolonged QRS duration. QRS durations >=100 msec in an aging rural population are associated with higher CASP measures. Our results also suggest in aging Australian rural populations CASP is likely to be elevated, possibly due to age related aortic stiffening. PMID- 26893944 TI - Future of the Smartphone for Patients and Healthcare Providers. PMID- 26893943 TI - Picking a bone with WISP1 (CCN4): new strategies against degenerative joint disease. AB - As the world's population continues to age, it is estimated that degenerative joint disease disorders such as osteoarthritis will impact at least 130 million individuals throughout the globe by the year 2050. Advanced age, obesity, genetics, gender, bone density, trauma, and a poor level of physical activity can lead to the onset and progression of osteoarthritis. However, factors that lead to degenerative joint disease and involve gender, genetics, epigenetic mechanisms, and advanced age are not within the control of an individual. Furthermore, current therapies including pain management, improved nutrition, and regular programs for exercise do not lead to the resolution of osteoarthritis. As a result, new avenues for targeting the treatment of osteoarthritis are desperately needed. Wnt1 inducible signaling pathway protein 1 (WISP1), a matricellular protein and a downstream target of the wingless pathway Wnt1, is one such target to consider that governs cellular protection, stem cell proliferation, and tissue regeneration in a number of disorders including bone degeneration. However, increased WISP1 expression also has been associated with the progression of osteoarthritis. WISP1 has an intricate relationship with a number of proliferative and protective pathways that include phosphoinositide 3 kinase (PI 3-K), protein kinase B (Akt), nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB), interleukin -6 (IL-6), transforming growth factor-beta, matrix metalloproteinase, small non-coding ribonucleic acids (RNAs), sirtuin silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and the mechanistic target of rapamycin (mTOR). Taken together, this complex association WISP1 holds with these signaling pathways necessitates a fine biological regulation of WISP1 activity that can offset the progression of degenerative joint disease, but not limit the cellular protective capabilities of the WISP1 pathway. PMID- 26893945 TI - Patient Accounting Systems: Are They Fit with the Users' Requirements? AB - OBJECTIVES: A patient accounting system is a subsystem of a hospital information system. This system like other information systems should be carefully designed to be able to meet users' requirements. The main aim of this research was to investigate users' requirements and to determine whether current patient accounting systems meet users' needs or not. METHODS: This was a survey study, and the participants were the users of six patient accounting systems used in 24 teaching hospitals. A stratified sampling method was used to select the participants (n = 216). The research instruments were a questionnaire and a checklist. The mean value of >=3 showed the importance of each data element and the capability of the system. RESULTS: Generally, the findings showed that the current patient accounting systems had some weaknesses and were able to meet between 70% and 80% of users' requirements. CONCLUSIONS: The current patient accounting systems need to be improved to be able to meet users' requirements. This approach can also help to provide hospitals with more usable and reliable financial information. PMID- 26893946 TI - Development and Evaluation of a Smartphone Application for Managing Gestational Diabetes Mellitus. AB - OBJECTIVES: The purpose of this study was to develop and evaluate an application (app) that provides tailored recommendations based on lifestyle and clinical data entered by the user. METHODS: Knowledge and functions required for the gestational diabetes mellitus (GDM) management app were extracted from clinical practice guidelines and evaluated through an online survey. Common and tailored recommendations were developed and evaluated with a content validity index. Algorithms to link tailored recommendations with a patient's data were developed and evaluated by experts. An Android-based app was developed and evaluated by comparing the process of data entry and recommendation retrieval and the usability of the app. After the app was revised, the user acceptance of the app was evaluated. RESULTS: Six domains of knowledge and 14 functions were extracted. Seven common and 49 tailored recommendations were developed. Nine lifestyle and clinical data elements were modeled. Eight algorithms with 18 decision nodes presenting tailored recommendations based on patient's data and 12 user interface screens were developed. All recommendations obtained from the use of app concurred with recommendations derived by algorithms. The average usability score was 69.5 out of 100. The user acceptance score with behavioral intention to use was 5.5, intrinsic motivation 4.3, the perceived ease of use score was 4.6, and the perceived usefulness score was 5.0 out of 7, respectively. CONCLUSIONS: The GDM management knowledge and tailored recommendations obtained in this study could be of help in managing GDM. PMID- 26893947 TI - Convergence of Health Level Seven Version 2 Messages to Semantic Web Technologies for Software-Intensive Systems in Telemedicine Trauma Care. AB - OBJECTIVES: To present the technical background and the development of a procedure that enriches the semantics of Health Level Seven version 2 (HL7v2) messages for software-intensive systems in telemedicine trauma care. METHODS: This study followed a multilevel model-driven approach for the development of semantically interoperable health information systems. The Pre-Hospital Trauma Life Support (PHTLS) ABCDE protocol was adopted as the use case. A prototype application embedded the semantics into an HL7v2 message as an eXtensible Markup Language (XML) file, which was validated against an XML schema that defines constraints on a common reference model. This message was exchanged with a second prototype application, developed on the Mirth middleware, which was also used to parse and validate both the original and the hybrid messages. RESULTS: Both versions of the data instance (one pure XML, one embedded in the HL7v2 message) were equally validated and the RDF-based semantics recovered by the receiving side of the prototype from the shared XML schema. CONCLUSIONS: This study demonstrated the semantic enrichment of HL7v2 messages for intensive-software telemedicine systems for trauma care, by validating components of extracts generated in various computing environments. The adoption of the method proposed in this study ensures the compliance of the HL7v2 standard in Semantic Web technologies. PMID- 26893948 TI - Intelligence System for Diagnosis Level of Coronary Heart Disease with K-Star Algorithm. AB - OBJECTIVES: Coronary heart disease is the leading cause of death worldwide, and it is important to diagnose the level of the disease. Intelligence systems for diagnosis proved can be used to support diagnosis of the disease. Unfortunately, most of the data available between the level/type of coronary heart disease is unbalanced. As a result system performance is low. METHODS: This paper proposes an intelligence systems for the diagnosis of the level of coronary heart disease taking into account the problem of data imbalance. The first stage of this research was preprocessing, which included resampled non-stratified random sampling (R), the synthetic minority over-sampling technique (SMOTE), clean data out of range attribute (COR), and remove duplicate (RD). The second step was the sharing of data for training and testing using a k-fold cross-validation model and training multiclass classification by the K-star algorithm. The third step was performance evaluation. The proposed system was evaluated using the performance parameters of sensitivity, specificity, positive prediction value (PPV), negative prediction value (NPV), area under the curve (AUC) and F-measure. RESULTS: The results showed that the proposed system provides an average performance with sensitivity of 80.1%, specificity of 95%, PPV of 80.1%, NPV of 95%, AUC of 87.5%, and F-measure of 80.1%. Performance of the system without consideration of data imbalance provide showed sensitivity of 53.1%, specificity of 88,3%, PPV of 53.1%, NPV of 88.3%, AUC of 70.7%, and F-measure of 53.1%. CONCLUSIONS: Based on these results it can be concluded that the proposed system is able to deliver good performance in the category of classification. PMID- 26893949 TI - New Alert Override Codes for the Drug Utilization Review System Derived from Outpatient Prescription Data from a Tertiary Teaching Hospital in Korea. AB - OBJECTIVES: This paper proposes new alert override reason codes that are improvements on existing Drug Utilization Review (DUR) codes based on an analysis of DUR alert override cases in a tertiary medical institution. METHODS: Data were obtained from a tertiary teaching hospital covering the period from April 1, 2012 to January 15, 2013. We analyzed cases in which doctors had used the 11 overlapping prescription codes provided by the Health Insurance Review and Assessment Service (HIRA) or had provided free-text reasons. RESULTS: We identified 27,955 alert override cases. Among these, 7,772 (27.8%) utilized the HIRA codes, and 20,183 (72.2%) utilized free-text reasons. According to the free text content analysis, 8,646 cases (42.8%) could be classified using the 11 HIRA codes, and 11,537 (57.2%) could not. In the unclassifiable cases, we identified the need for codes for "prescription relating to operation" and "emergency situations." Two overlapping prescription codes required removal because they were not used. Codes A, C, F, H, I, and J (for drug non-administration cases) explained surrounding situations in too much detail, making differentiation between them difficult. These 6 codes were merged into code J4: "patient was not taking/will not take the medications involved in the DDI." Of the 11 HIRA codes, 6 were merged into a single code, 2 were removed, and 2 were added, yielding 6 alert override codes. We could codify 23,550 (84.2%) alert override cases using these codes. CONCLUSIONS: These new codes will facilitate the use of the drug drug interactions alert override in the current DUR system. For further study, an appropriate evaluation should be conducted with prescribing clinicians. PMID- 26893950 TI - Clinical Alarms in Intensive Care Units: Perceived Obstacles of Alarm Management and Alarm Fatigue in Nurses. AB - OBJECTIVES: The purpose of this descriptive study was to investigate the current situation of clinical alarms in intensive care unit (ICU), nurses' recognition of and fatigue in relation to clinical alarms, and obstacles in alarm management. METHODS: Subjects were ICU nurses and devices from 48 critically ill patient cases. Data were collected through direct observation of alarm occurrence and questionnaires that were completed by the ICU nurses. The observation time unit was one hour block. One bed out of 56 ICU beds was randomly assigned to each observation time unit. RESULTS: Overall 2,184 clinical alarms were counted for 48 hours of observation, and 45.5 clinical alarms occurred per hour per subject. Of these, 1,394 alarms (63.8%) were categorized as false alarms. The alarm fatigue score was 24.3 +/- 4.0 out of 35. The highest scoring item was "always get bothered due to clinical alarms". The highest scoring item in obstacles was "frequent false alarms, which lead to reduced attention or response to alarms". CONCLUSIONS: Nurses reported that they felt some fatigue due to clinical alarms, and false alarms were also obstacles to proper management. An appropriate hospital policy should be developed to reduce false alarms and nurses' alarm fatigue. PMID- 26893952 TI - Correction: Prerequisites for Effective Implementation of Telemedicine: Focusing on Current Situation in Korea. AB - [This corrects the article on p. 251 in vol. 21, PMID: 26618031.]. PMID- 26893951 TI - Conversion and Data Quality Assessment of Electronic Health Record Data at a Korean Tertiary Teaching Hospital to a Common Data Model for Distributed Network Research. AB - OBJECTIVES: A distributed research network (DRN) has the advantages of improved statistical power, and it can reveal more significant relationships by increasing sample size. However, differences in data structure constitute a major barrier to integrating data among DRN partners. We describe our experience converting Electronic Health Records (EHR) to the Observational Health Data Sciences and Informatics (OHDSI) Common Data Model (CDM). METHODS: We transformed the EHR of a hospital into Observational Medical Outcomes Partnership (OMOP) CDM ver. 4.0 used in OHDSI. All EHR codes were mapped and converted into the standard vocabulary of the CDM. All data required by the CDM were extracted, transformed, and loaded (ETL) into the CDM structure. To validate and improve the quality of the transformed dataset, the open-source data characterization program ACHILLES was run on the converted data. RESULTS: Patient, drug, condition, procedure, and visit data from 2.07 million patients who visited the subject hospital from July 1994 to November 2014 were transformed into the CDM. The transformed dataset was named the AUSOM. ACHILLES revealed 36 errors and 13 warnings in the AUSOM. We reviewed and corrected 28 errors. The summarized results of the AUSOM processed with ACHILLES are available at http://ami.ajou.ac.kr:8080/. CONCLUSIONS: We successfully converted our EHRs to a CDM and were able to participate as a data partner in an international DRN. Converting local records in this manner will provide various opportunities for researchers and data holders. PMID- 26893953 TI - Pain management in patients receiving palliative care. PMID- 26893954 TI - Solid Dose Form of Metformin with Ethyl Eicosapentaenoic Acid Does Not Improve Metformin Plasma Availability. AB - BACKGROUND: The purpose of the study was to investigate effects of ethyl eicosapentaenoic acid on pharmacokinetics of metformin. Pharmacokinetic profiles of metformin and ethyl eicosapentaenoic acid when delivered separately or together in solid dose form were investigated and compared to determine whether the solid dose resulted in an altered metforminpharmacokinetics when given with or without food. METHODS: A single-center, open-label, repeated dose study investigated the pharmacokinetic (PK) profile of metformin when administered in solid dose form with ethyl eicosapentaenoic acid compared to co-administration with icosapent ethyl, an ester of eicosapentaenoic acid and ethyl alcohol used to treat severe hypertriglyceridemia with metformin hydrochloride. Non-compartmental PK methods were used to compare area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax) between patients randomized to either the ester or separate medications group under both fasting and fed conditions. RESULTS: Using these two PK parameters, results showed that metformin availability was higher under fasting conditions when delivered separately from icosapent ethyl. There were no group differences in the fed condition. CONCLUSIONS: The solid dose form of metformin and ethyl eicosapentaenoic acid did not improve the pharmacokinetics of metformin in terms of plasma availability, suggesting that little is to be gained over the separate administration of ethyl eicosapentaenoic acid and metformin hydrochloride. PMID- 26893955 TI - Evolution of universal review and disclosure of MRI reports to research participants. AB - BACKGROUND: Although incidental findings (IF) are commonly encountered in neuroimaging research, there is no consensus regarding what to do with them. Whether researchers are obligated to review scans for IF, or if such findings should be disclosed to research participants at all, is controversial. Objective data are required to inform reasonable research policy; unfortunately, such data are lacking in the published literature. This manuscript summarizes the development of a radiology review and disclosure system in place at a neuroimaging research institute and its impact on key stakeholders. METHODS: The evolution of a universal radiology review system is described, from inception to its current status. Financial information is reviewed, and stakeholder impact is characterized through surveys and interviews. RESULTS: Consistent with prior reports, 34% of research participants had an incidental finding identified, of which 2.5% required urgent medical attention. A total of 87% of research participants wanted their magnetic resonance imaging (MRI) results regardless of clinical significance and 91% considered getting an MRI report a benefit of study participation. A total of 63% of participants who were encouraged to see a doctor about their incidental finding actually followed up with a physician. Reasons provided for not following-up included already knowing the finding existed (14%), not being able to afford seeing a physician (29%), or being reassured after speaking with the institute's Medical Director (43%). Of those participants who followed the recommendation to see a physician, nine (38%) required further diagnostic testing. No participants, including those who pursued further testing, regretted receiving their MRI report, although two participants expressed concern about the excessive personal cost. The current cost of the radiology review system is about $23 per scan. CONCLUSIONS: It is possible to provide universal radiology review of research scans through a system that is cost-effective, minimizes investigator burden, and does not overwhelm local healthcare resources. PMID- 26893957 TI - Effects of early and late cheiloplasty on anterior part of maxillary dental arch development in infants with unilateral complete cleft lip and palate. AB - Objectives. The objective of this study is to compare the impact of early and late reconstruction of complete unilateral cleft lip and palate on the growth and development of the front of the dentoalveolar arch. Methods. This study was carried out in the years 2012-2015 at the Clinic of Plastic, Reconstructive and Aesthetic Surgery in Banska Bystrica. Infants with unilateral complete cleft lip and palate were divided into 2 groups according to the timing of lip reconstruction. Group A consisted of infants with early lip reconstruction realised in the first 14 days of life. Group B consisted of infants with later lip reconstruction-realised in the third month of age. Maxillary dental casts were obtained for each child in four periods-in the first 14 days of life, in the third month, in the sixth month and in the age of one year. These were followed by the identification, measurement and evaluation of anthropometric parameters. Results. Significant differences were occurred after the reconstruction of the lips in linear and angle measurements between infants in the A and B groups. Conclusion. The early surgical reconstruction of the lips in the first 14 days of life has a positive effect on the growth and development of the anterior segment of the dentoalveolar arch. Early lip reconstruction forms a continuous pressure on the frontal segment, resulting in the earlier remedy of anatomical properties and creates appropriate conditions for the best development of this area. PMID- 26893958 TI - Comparison of upper body strength gains between men and women after 10 weeks of resistance training. AB - Resistance training (RT) offers benefits to both men and women. However, the studies about the differences between men and women in response to an RT program are not conclusive and few data are available about upper body strength response. The aim of this study was to compare elbow flexor strength gains in men and women after 10 weeks of RT. Forty-four college-aged men (22.63 +/- 2.34 years) and forty-seven college-aged women (21.62 +/- 2.96 years) participated in the study. The RT program was performed two days a week for 10 weeks. Before and after the training period, peak torque (PT) of the elbow flexors was measured with an isokinetic dynamometer. PT values were higher in men in comparison to women in pre- and post-tests (p < 0.01). Both males and females significantly increased elbow flexor strength (p < 0.05); however, strength changes did not differ between genders after 10 weeks of RT program (11.61 and 11.76% for men and women, respectively; p > 0.05). Effect sizes were 0.57 and 0.56 for men and women, respectively. In conclusion, the present study suggests that men and women have a similar upper body strength response to RT. PMID- 26893956 TI - On the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines. AB - Over the past 60 years, the Mycobacterium bovis bacille Calmette-Guerin (BCG) has been used worldwide to prevent tuberculosis (TB). However, BCG has shown a very variable efficacy in different trials, offering a wide range of protection in adults against pulmonary TB. One of the most accepted hypotheses to explain these inconsistencies points to the existence of a pre-existing immune response to antigens that are common to environmental sources of mycobacterial antigens and Mycobacterium tuberculosis. Specifically, two different mechanisms have been hypothesized to explain this phenomenon: the masking and the blocking effects. According to masking hypothesis, previous sensitization confers some level of protection against TB that masks vaccine's effects. In turn, the blocking hypothesis postulates that previous immune response prevents vaccine taking of a new TB vaccine. In this work we introduce a series of models to discriminate between masking and blocking mechanisms and address their relative likelihood. We apply our methodology to the data reported by BCG-REVAC clinical trials, which were specifically designed for studying BCG efficacy variability. Our results yield estimates that are consistent with high levels of blocking (41% in Manaus 95% CI [14-68]- and 96% in Salvador -95% CI [52-100]-). Moreover, we also show that masking does not play any relevant role in modifying vaccine's efficacy either alone or in addition to blocking. The quantification of these effects around a plausible model constitutes a relevant step towards impact evaluation of novel anti-tuberculosis vaccines, which are susceptible of being affected by similar effects, especially if applied on individuals previously exposed to mycobacterial antigens. PMID- 26893959 TI - Taxonomic and systematic revisions to the North American Nimravidae (Mammalia, Carnivora). AB - The Nimravidae is a family of extinct carnivores commonly referred to as "false saber-tooth cats." Since their initial discovery, they have prompted difficulty in taxonomic assignments and number of valid species. Past revisions have only examined a handful of genera, while recent advances in cladistic and morphometric analyses have granted us additional avenues to answering questions regarding our understanding of valid nimravid taxa and their phylogenetic relationships. To resolve issues of specific validity, the phylogenetic species concept (PSC) was utilized to maintain consistency in diagnosing valid species, while simultaneously employing character and linear morphometric analyses for confirming the validity of taxa. Determined valid species and taxonomically informative characters were then employed in two differential cladistic analyses to create competing hypotheses of interspecific relationships. The results suggest the validity of twelve species and six monophyletic genera. The first in depth reviews of Pogonodon and Dinictis returned two valid species (P. platycopis, P. davisi) for the former, while only one for the latter (D. felina). The taxonomic validity of Nanosmilus is upheld. Two main clades with substantial support were returned for all cladistic analyses, the Hoplophoneini and Nimravini, with ambiguous positions relative to these main clades for the European taxa: Eofelis, Dinailurictis bonali, and Quercylurus major; and the North American taxa Dinictis and Pogonodon. Eusmilus is determined to represent a non-valid genus for North American taxa, suggesting non-validity for Old World nimravid species as well. Finally, Hoplophoneus mentalis is found to be a junior synonym of Hoplophoneus primaevus, while the validity of Hoplophoneus oharrai is reinstated. PMID- 26893960 TI - Effectiveness of adaptive silverware on range of motion of the hand. AB - Background. Hand function is essential to a person's self-efficacy and greatly affects quality of life. Adapted utensils with handles of increased diameters have historically been used to assist individuals with arthritis or other hand disabilities for feeding, and other related activities of daily living. To date, minimal research has examined the biomechanical effects of modified handles, or quantified the differences in ranges of motion (ROM) when using a standard versus a modified handle. The aim of this study was to quantify the ranges of motion (ROM) required for a healthy hand to use different adaptive spoons with electrogoniometry for the purpose of understanding the physiologic advantages that adapted spoons may provide patients with limited ROM. Methods. Hand measurements included the distal interphalangeal joint (DIP), proximal interphalangeal joint (PIP), and metacarpophalangeal joint (MCP) for each finger and the interphalangeal (IP) and MCP joint for the thumb. Participants were 34 females age 18-30 (mean age 20.38 +/- 1.67) with no previous hand injuries or abnormalities. Participants grasped spoons with standard handles, and spoons with handle diameters of 3.18 cm (1.25 inch), and 4.45 cm (1.75 inch). ROM measurements were obtained with an electrogoniometer to record the angle at each joint for each of the spoon handle sizes. Results. A 3 * 3 * 4 repeated measures ANOVA (Spoon handle size by Joint by Finger) found main effects on ROM of Joint (F(2, 33) = 318.68, Partial eta (2) = .95, p < .001), Spoon handle size (F(2, 33) = 598.73, Partial eta (2) = .97, p < .001), and Finger (F(3, 32) = 163.83, Partial eta (2) = .94, p < .001). As the spoon handle diameter size increased, the range of motion utilized to grasp the spoon handle decreased in all joints and all fingers (p < 0.01). Discussion. This study confirms the hypothesis that less range of motion is required to grip utensils with larger diameter handles, which in turn may reduce challenges for patients with limited ROM of the hand. PMID- 26893961 TI - Improving the peer-review process and editorial quality: key errors escaping the review and editorial process in top scientific journals. AB - We apply a novel mistake index to assess trends in the proportion of corrections published between 1993 and 2014 in Nature, Science and PNAS. The index revealed a progressive increase in the proportion of corrections published in these three high-quality journals. The index appears to be independent of the journal impact factor or the number of items published, as suggested by a comparative analyses among 16 top scientific journals of different impact factors and disciplines. A more detailed analysis suggests that the trend in the time-to-correction increased significantly over time and also differed among journals (Nature 233 days; Science 136 days; PNAS 232 days). A detailed review of 1,428 errors showed that 60% of corrections were related to figures, authors, references or results. According to the three categories established, 34.7% of the corrections were considered mild, 47.7% moderate and 17.6% severe, also differing among journals. Errors occurring during the printing process were responsible for 5% of corrections in Nature, 3% in Science and 18% in PNAS. The measurement of the temporal trends in the quality of scientific manuscripts can assist editors and reviewers in identifying the most common mistakes, increasing the rigor of peer review and improving the quality of published scientific manuscripts. PMID- 26893962 TI - The effect of agmatine on trichothecene type B and zearalenone production in Fusarium graminearum, F. culmorum and F. poae. AB - Agmatine and other putrescines are known for being strong inducers of deoxynivalenol (DON) production in Fusarium graminearum. Other important species produce DON and/or other trichothecene type B toxins (3 acetylated DON, 15 acetylated DON, Fusarenon-X, Nivalenol), such as F. culmorum and F. poae. In order to verify whether the mechanism of the regulation of trichothecene type B induction by agmatine is shared by different species of Fusarium, we tested the hypothesis on 19 strains belonging to 3 Fusarium species (F. graminearum, F. culmorum, F. poae) with diverse genetic chemotypes (3ADON, 15ADON, NIV) by measuring trichothecene B toxins such as DON, NIV, Fusarenon-X, 3ADON and 15ADON. Moreover, we tested whether other toxins like zearalenone were also boosted by agmatine. The trichothecene type B boosting effect was observed in the majority of strains (13 out of 19) in all the three species. Representative strains from all three genetic chemotypes were able to boost toxin production after agmatine treatment. We identified the non-responding strains to the agmatine stimulus, which may contribute to deciphering the regulatory mechanisms that link toxin production to agmatine (and, more generally, polyamines). PMID- 26893963 TI - A method to construct a points system to predict cardiovascular disease considering repeated measures of risk factors. AB - Current predictive models for cardiovascular disease based on points systems use the baseline situation of the risk factors as independent variables. These models do not take into account the variability of the risk factors over time. Predictive models for other types of disease also exist that do consider the temporal variability of a single biological marker in addition to the baseline variables. However, due to their complexity these other models are not used in daily clinical practice. Bearing in mind the clinical relevance of these issues and that cardiovascular diseases are the leading cause of death worldwide we show the properties and viability of a new methodological alternative for constructing cardiovascular risk scores to make predictions of cardiovascular disease with repeated measures of the risk factors and retaining the simplicity of the points systems so often used in clinical practice (construction, statistical validation by simulation and explanation of potential utilization). We have also applied the system clinically upon a set of simulated data solely to help readers understand the procedure constructed. PMID- 26893964 TI - Bodily action penetrates affective perception. AB - Fantoni & Gerbino (2014) showed that subtle postural shifts associated with reaching can have a strong hedonic impact and affect how actors experience facial expressions of emotion. Using a novel Motor Action Mood Induction Procedure (MAMIP), they found consistent congruency effects in participants who performed a facial emotion identification task after a sequence of visually-guided reaches: a face perceived as neutral in a baseline condition appeared slightly happy after comfortable actions and slightly angry after uncomfortable actions. However, skeptics about the penetrability of perception (Zeimbekis & Raftopoulos, 2015) would consider such evidence insufficient to demonstrate that observer's internal states induced by action comfort/discomfort affect perception in a top-down fashion. The action-modulated mood might have produced a back-end memory effect capable of affecting post-perceptual and decision processing, but not front-end perception. Here, we present evidence that performing a facial emotion detection (not identification) task after MAMIP exhibits systematic mood-congruent sensitivity changes, rather than response bias changes attributable to cognitive set shifts; i.e., we show that observer's internal states induced by bodily action can modulate affective perception. The detection threshold for happiness was lower after fifty comfortable than uncomfortable reaches; while the detection threshold for anger was lower after fifty uncomfortable than comfortable reaches. Action valence induced an overall sensitivity improvement in detecting subtle variations of congruent facial expressions (happiness after positive comfortable actions, anger after negative uncomfortable actions), in the absence of significant response bias shifts. Notably, both comfortable and uncomfortable reaches impact sensitivity in an approximately symmetric way relative to a baseline inaction condition. All of these constitute compelling evidence of a genuine top-down effect on perception: specifically, facial expressions of emotion are penetrable by action-induced mood. Affective priming by action valence is a candidate mechanism for the influence of observer's internal states on properties experienced as phenomenally objective and yet loaded with meaning. PMID- 26893966 TI - Four-dimensional noise reduction using the time series of medical computed tomography datasets with short interval times: a static-phantom study. AB - Backgrounds. This study examines the hypothesis that four-dimensional noise reduction (4DNR) with short interval times reduces noise in cardiac computed tomography (CCT) using "padding" phases. Furthermore, the capability of reducing the reduction dose in CCT using this post-processing technique was assessed. Methods. Using base and quarter radiation doses for CCT (456 and 114 mAs/rot with 120 kVp), a static phantom was scanned ten times with retrospective electrocardiogram gating, and 4DNR with short interval times (50 ms) was performed using a post-processing technique. Differences in the computed tomography (CT) attenuation, contrast-to-noise ratio (CNR) and spatial resolution with modulation transfer function in each dose image obtained with and without 4DNR were assessed by conducting a Tukey-Kramer's test and non-inferiority test. Results. For the base dose, by using 4DNR, the CNR was improved from 1.18 +/- 0.15 to 2.08 +/- 0.20 (P = 0.001), while the CT attenuation and spatial resolution of the image of 4DNR did not were significantly inferior to those of reference image (P < 0.001). CNRs of the quarter-dose image in 4DNR also improved to 1.28 +/- 0.11, and were not inferior to those of the non-4DNR images of the base dose (P < 0.001). Conclusions. 4DNR with short interval times significantly reduced noise. Furthermore, applying this method to CCT would have the potential of reducing the radiation dose by 75%, while maintaining a similar image noise level. PMID- 26893967 TI - Testing the effects of perimeter fencing and elephant exclosures on lion predation patterns in a Kenyan wildlife conservancy. AB - The use of fences to segregate wildlife can change predator and prey behaviour. Predators can learn to incorporate fencing into their hunting strategies and prey can learn to avoid foraging near fences. A twelve-strand electric predator-proof fence surrounds our study site. There are also porous one-strand electric fences used to create exclosures where elephant (and giraffe) cannot enter in order to protect blocs of browse vegetation for two critically endangered species, the black rhinoceros (Diceros bicornis) and the Grevy's zebra (Equus grevyi). The denser vegetation in these exclosures attracts both browsing prey and ambush predators. In this study we examined if lion predation patterns differed near the perimeter fencing and inside the elephant exclosures by mapping the location of kills. We used a spatial analysis to compare the predation patterns near the perimeter fencing and inside the exclosures to predation in the rest of the conservancy. Predation was not over-represented near the perimeter fence but the pattern of predation near the fence suggests that fences may be a contributing factor to predation success. Overall, we found that predation was over represented inside and within 50 m of the exclosures. However, by examining individual exclosures in greater detail using a hot spot analysis, we found that only a few exclosures contained lion predation hot spots. Although some exclosures provide good hunting grounds for lions, we concluded that exclosures did not necessarily create prey-traps per se and that managers could continue to use this type of exclusionary fencing to protect stands of dense vegetation. PMID- 26893965 TI - Sorted gene genealogies and species-specific nonsynonymous substitutions point to putative postmating prezygotic isolation genes in Allonemobius crickets. AB - In the Allonemobius socius complex of crickets, reproductive isolation is primarily accomplished via postmating prezygotic barriers. We tested seven protein-coding genes expressed in the male ejaculate for patterns of evolution consistent with a putative role as postmating prezygotic isolation genes. Our recently diverged species generally lacked sequence variation. As a result, omega based tests were only mildly successful. Some of our genes showed evidence of elevated omega values on the internal branches of gene trees. In a couple of genes, these internal branches coincided with both species branching events of the species tree, between A. fasciatus and the other two species, and between A. socius and A. sp. nov. Tex. In comparison, more successful approaches were those that took advantage of the varying degrees of lineage sorting and allele sharing among our young species. These approaches were particularly powerful within the contact zone. Among the genes we tested we found genes with genealogies that indicated relatively advanced degrees of lineage sorting across both allopatric and contact zone alleles. Within a contact zone between two members of the species complex, only a subset of genes maintained allelic segregation despite evidence of ongoing gene flow in other genes. The overlap in these analyses was arginine kinase (AK) and apolipoprotein A-1 binding protein (APBP). These genes represent two of the first examples of sperm maturation, capacitation, and motility proteins with fixed non-synonymous substitutions between species specific alleles that may lead to postmating prezygotic isolation. Both genes express ejaculate proteins transferred to females during copulation and were previously identified through comparative proteomics. We discuss the potential function of these genes in the context of the specific postmating prezygotic isolation phenotype among our species, namely conspecific sperm precedence and the superior ability of conspecific males to induce oviposition in females. PMID- 26893969 TI - Bagworm bags as portable armour against invertebrate predators. AB - Some animals have evolved the use of environmental materials as "portable armour" against natural enemies. Portable bags that bagworm larvae (Lepidoptera: Psychidae) construct using their own silk and plant parts are generally believed to play an important role as a physical barrier against natural enemies. However, no experimental studies have tested the importance of bags as portable armour against predators. To clarify the defensive function, I studied the bagworm Eumeta minuscula and a potential predator Calosoma maximoviczi (Coleoptera: Carabidae). Under laboratory conditions, all bagworm larvae were attacked by carabid adults, but successfully defended themselves against the predators' mandibles using their own bags. The portable bags, which are composed mainly of host plant twigs, may function as a physical barrier against predator mandibles. To test this hypothesis, I removed the twig bags and replaced some with herb leaf bags; all bag-removed larvae were easily caught and predated by carabids, while all bag-replaced larvae could successfully defend themselves against carabid attacks. Therefore, various types of portable bags can protect bagworm larvae from carabid attacks. This is the first study to test the defensive function of bagworm portable bags against invertebrate predators. PMID- 26893968 TI - Heat shock protein 90 is involved in the regulation of HMGA2-driven growth and epithelial-to-mesenchymal transition of colorectal cancer cells. AB - High Mobility Group AT-hook 2 (HMGA2) is a nonhistone chromatin-binding protein which acts as a transcriptional regulating factor involved in gene transcription. In particular, overexpression of HMGA2 has been demonstrated to associate with neoplastic transformation and tumor progression in Colorectal Cancer (CRC). Thus, HMGA2 is a potential therapeutic target in cancer therapy. Heat Shock Protein 90 (Hsp90) is a chaperone protein required for the stability and function for a number of proteins that promote the growth, mobility, and survival of cancer cells. Moreover, it has shown strong positive connections were observed between Hsp90 inhibitors and CRC, which indicated their potential for use in CRC treatment by using combination of data mining and experimental designs. However, little is known about the effect of Hsp90 inhibition on HMGA2 protein expression in CRC. In this study, we tested the hypothesis that Hsp90 may regulate HMGA2 expression and investigated the relationship between Hsp90 and HMGA2 signaling. The use of the second-generation Hsp90 inhibitor, NVP-AUY922, considerably knocked down HMGA2 expression, and the effects of Hsp90 and HMGA2 knockdown were similar. In addition, Hsp90 knockdown abrogates colocalization of Hsp90 and HMGA2 in CRC cells. Moreover, the suppression of HMGA2 protein expression in response to NVP-AUY922 treatment resulted in ubiquitination and subsequent proteasome dependant degradation of HMGA2. Furthermore, RNAi-mediated silencing of HMGA2 reduced the survival of CRC cells and increased the sensitivity of these cells to chemotherapy. Finally, we found that the NVP-AUY922-dependent mitigation of HMGA2 signaling occurred also through indirect reactivation of the tumor suppressor microRNA (miRNA), let-7a, or the inhibition of ERK-regulated HMGA2 involved in regulating the growth of CRC cells. Collectively, our studies identify the crucial role for the Hsp90-HMGA2 interaction in maintaining CRC cell survival and migration. These findings have significant implications for inhibition HMGA2 dependent tumorigenesis by clinically available Hsp90 inhibitors. PMID- 26893970 TI - Spatial structure arising from neighbour-dependent bias in collective cell movement. AB - Mathematical models of collective cell movement often neglect the effects of spatial structure, such as clustering, on the population dynamics. Typically, they assume that individuals interact with one another in proportion to their average density (the mean-field assumption) which means that cell-cell interactions occurring over short spatial ranges are not accounted for. However, in vitro cell culture studies have shown that spatial correlations can play an important role in determining collective behaviour. Here, we take a combined experimental and modelling approach to explore how individual-level interactions give rise to spatial structure in a moving cell population. Using imaging data from in vitro experiments, we quantify the extent of spatial structure in a population of 3T3 fibroblast cells. To understand how this spatial structure arises, we develop a lattice-free individual-based model (IBM) and simulate cell movement in two spatial dimensions. Our model allows an individual's direction of movement to be affected by interactions with other cells in its neighbourhood, providing insights into how directional bias generates spatial structure. We consider how this behaviour scales up to the population level by using the IBM to derive a continuum description in terms of the dynamics of spatial moments. In particular, we account for spatial correlations between cells by considering dynamics of the second spatial moment (the average density of pairs of cells). Our numerical results suggest that the moment dynamics description can provide a good approximation to averaged simulation results from the underlying IBM. Using our in vitro data, we estimate parameters for the model and show that it can generate similar spatial structure to that observed in a 3T3 fibroblast cell population. PMID- 26893971 TI - Is type-D personality trait(s) or state? An examination of type-D temporal stability in older Israeli adults in the community. AB - Background. Type D personality was suggested as a marker of poorer prognosis for patients of cardiovascular disease. It is defined by having a score of 10 or more on both sub-scales of the DS14 questionnaire, Social Inhibition (SI) and Negative Affectivity (NA). As Type D was designed to predict risk, its temporal stability is of prime importance. Methods. Participants in the current study were 285 community volunteers, who completed the DS14, and other personality scales, at a mean interval of six years. Results. The prevalence of Type D did not change. The component traits of Type D showed rank order stability. Type D caseness temporal stability was improved by using the sub-scales product as a criterion. Logistic hierarchical regression predicting Type D classification from Time1 demonstrated that the best predictors were Time1 scores on NA and SI, with the character trait of Cooperation, and the alexithymia score adding some predictive power. Conclusions. The temporal stability of the component traits, and of the prevalence of Type D were excellent. Temporal stability of Type D caseness may be improved by using a product threshold, rather than the current rule. Research is required in order to formulate the optimal timing for Type D measurement for predictive purposes. PMID- 26893972 TI - The furculae of the dromaeosaurid dinosaur Dakotaraptor steini are trionychid turtle entoplastra. AB - Dakotaraptor steini is a recently described dromaeosaurid dinosaur from the Upper Cretaceous (Maastrichtian) Hell Creek Formation of South Dakota. Included within the D. steini hypodigm are three elements originally identified as furculae, one of which was made part of the holotype specimen. We show that the elements described as D. steini 'furculae' are not theropod dinosaur furculae, but are rather trionychid turtle entoplastra referable to cf. Axestemys splendida. The hypodigm of D. steini should be adjusted accordingly. PMID- 26893973 TI - Apparent source levels and active communication space of whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in the Pearl River Estuary and Beibu Gulf, China. AB - Background. Knowledge of species-specific vocalization characteristics and their associated active communication space, the effective range over which a communication signal can be detected by a conspecific, is critical for understanding the impacts of underwater acoustic pollution, as well as other threats. Methods. We used a two-dimensional cross-shaped hydrophone array system to record the whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in shallow-water environments of the Pearl River Estuary (PRE) and Beibu Gulf (BG), China. Using hyperbolic position fixing, which exploits time differences of arrival of a signal between pairs of hydrophone receivers, we obtained source location estimates for whistles with good signal-to-noise ratio (SNR >=10 dB) and not polluted by other sounds and back-calculated their apparent source levels (ASL). Combining with the masking levels (including simultaneous noise levels, masking tonal threshold, and the Sousa auditory threshold) and the custom made site-specific sound propagation models, we further estimated their active communication space (ACS). Results. Humpback dolphins produced whistles with average root-mean-square ASL of 138.5 +/- 6.8 (mean +/- standard deviation) and 137.2 +/- 7.0 dB re 1 uPa in PRE (N = 33) and BG (N = 209), respectively. We found statistically significant differences in ASLs among different whistle contour types. The mean and maximum ACS of whistles were estimated to be 14.7 +/- 2.6 (median +/- quartile deviation) and 17.1+/- 3.5 m in PRE, and 34.2 +/- 9.5 and 43.5 +/- 12.2 m in BG. Using just the auditory threshold as the masking level produced the mean and maximum ACSat of 24.3 +/- 4.8 and 35.7 +/- 4.6 m for PRE, and 60.7 +/- 18.1 and 74.3 +/- 25.3 m for BG. The small ACSs were due to the high ambient noise level. Significant differences in ACSs were also observed among different whistle contour types. Discussion. Besides shedding some light for evaluating appropriate noise exposure levels and information for the regulation of underwater acoustic pollution, these baseline data can also be used for aiding the passive acoustic monitoring of dolphin populations, defining the boundaries of separate groups in a more biologically meaningful way during field surveys, and guiding the appropriate approach distance for local dolphin-watching boats and research boat during focal group following. PMID- 26893975 TI - Spindle Cell Lipoma of the Neck: Review of the Literature and Case Report. AB - Spindle cell lipomas (SCL) are benign, slow growing tumors arising most frequently in the subcutaneous tissue of the upper back, posterior neck, and shoulders in males aged 40-70 years. Local excision is generally curative. Classification of lipomatous tumors has progressed recently, and tumors of similar morphology and unusual presentation are increasingly reported, thereby making correct diagnosis even more vital. SCL require pathologic differentiation from liposarcoma, other spindle cell neoplasms, and myxoid lesions for treatment purposes. Cytology, histology, and cytogenetics, in conjunction with clinical presentation, are paramount in arriving at the correct diagnosis of spindle cell lipoma. We present a case report with characteristics typical of an SCL along with a literature review to further elucidate the diagnosis and surgical treatment of this soft tissue tumor. PMID- 26893974 TI - Validation of reference genes for quantitative RT-PCR normalization in Suaeda aralocaspica, an annual halophyte with heteromorphism and C4 pathway without Kranz anatomy. AB - Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful analytical technique for the measurement of gene expression, which depends on the stability of the reference gene used for data normalization. Suaeda aralocaspica, an annual halophyte with heteromorphic seeds and possessing C4 photosynthesis pathway without Kranz anatomy, is an ideal plant species to identify stress tolerance-related genes and compare relative expression at transcriptional level. So far, no molecular information is available for this species. In the present study, six traditionally used reference genes were selected and their expression stability in two types of seeds of S. aralocaspica under different experimental conditions was evaluated. Three analytical programs, geNorm, NormFinder and BestKeeper, were used to assess and rank the stability of reference gene expression. Results revealed that although some reference genes may display different transcriptional profiles between the two types of seeds, beta-TUB and GAPDH appeared to be the most suitable references under different developmental stages and tissues. GAPDH was the appropriate reference gene under different germination time points and salt stress conditions, and ACTIN was suitable for various abiotic stress treatments for the two types of seeds. For all the sample pools, beta-TUB served as the most stable reference gene, whereas 18S rRNA and 28S rRNA performed poorly and presented as the least stable genes in our study. UBQ seemed to be unsuitable as internal control under different salt treatments. In addition, the expression of a photosynthesis-related gene (PPDK) of C4 pathway and a salt tolerance-related gene (SAT) of S. aralocaspica were used to validate the best performance reference genes. This is the first systematic comparison of reference gene selection for qRT-PCR work in S. aralocaspica and these data will facilitate further studies on gene expression in this species and other euhalophytes. PMID- 26893976 TI - Long-term Patency of Primary Arterial Repair and the Modified Cold Intolerance Symptom Severity Questionnaire. AB - BACKGROUND: The goal of this study was to assess the long-term arterial patency of repaired arteries in the upper extremity and any morbidity resulting from the subsequent occlusion of these vessels. Concurrently, a new questionnaire, the modified Cold Intolerance Symptom Severity (mod CISS) questionnaire, was developed to allow for better assessment of cold intolerance. METHODS: Thirteen patients who had undergone repair of the radial (4 patients), ulnar (6 patients), brachial (1 patient), digital (1), and an undefined lower arm artery (1) were examined using questionnaires, physical examination, and high-resolution ultrasound. RESULTS: Outcome measures that were statistically significantly worse in the group of patients who presented with nerve injuries included cold intolerance symptoms, Disabilities of the Arm, Shoulder, and Hand score, Michigan Hand Questionnaire, and grip strength (middle setting on dynamometer). The results from the mod CISS correlated with high statistical significance with the results of the CISS score for the injured hand. Of note, wrist extension was significantly better with patent arteries. CONCLUSIONS: Sixty-seven percent of arterial repairs remained patent at 6 years (mean) follow-up. The presence of nerve injury has a higher impact on the outcome metrics assessed in this study than arterial patency. Our modification of the CISS score enhances its utility as a survey of cold intolerance. PMID- 26893978 TI - Use of Video Clips to Assess the Outcomes of Bilateral Hand Transplantation. AB - Given the initial success of hand transplantation, there has been increased interest in determining functional independence and activities of daily living after hand transplantation. However, the metrics and methodologies used to study these outcomes have not yet been standardized. The goal of this article was to assess the role of video clips in assessing the outcomes of bilateral hand transplantation. We have performed 3 bilateral hand transplantations at our institution. Video clips were taken at standardized time points on our index bilateral hand transplantation patient, and the patient sent multiple home-video clips demonstrating new aspects of function when these improvements have occurred. The index patient demonstrated functional independence and activity of daily living performance without assistance in video clips ranging from 9 months to 2.5 years posttransplantation. He completed the 9-hole peg test with his left hand at 9 months follow-up and with both the hands by 1.5 years. His own video clips demonstrated his ability to perform spontaneous tasks including lawn mowing, driving and swimming. In our experience, the video tools aid in assessing outcomes of hand transplantation and may be incorporated along with multiple objective scoring tests. They can also be used to generate additional standardized tests for functional assessment and may allow retrospective grading as new scoring systems are developed. PMID- 26893977 TI - The Importance of Hand Appearance as a Patient-Reported Outcome in Hand Surgery. AB - Hand appearance is meaningful to patients because hands are an essential part of human interactions, communication, and social integration. Recent literature indicates that hand aesthetics is an important, measurable patient-reported outcome. In hand surgery, several outcome instruments exist that accurately measure functional outcomes, but aesthetics is often overlooked or imprecisely measured. This makes comparison of disease burden and effectiveness of therapies, as they pertain to aesthetics, difficult. This special topic article outlines the aesthetic features of the hand, how literature is evaluating the appearance of the hand in outcomes research, and proposes a novel approach to assessing hand aesthetics. PMID- 26893979 TI - A Practical Surgical Technique to Expose the Mental Nerve in Narrowing Genioplasty. AB - In this article, the authors present a practical surgical technique using the anatomical character of the inferior alveolar nerve to fully expose the mental nerve (MN) in narrowing genioplasty. During the procedure, a rectangular mandibular outer cortex adjacent to the mental foramen is removed before the osteotomy. The objective is to avoid the injury of the MN from the reciprocating saw or bur and offer abundant space for the surgical operation. The technique has a minimal learning curve and will be useful to plastic surgeons to minimize unintentional cutting or pulling injury to the MN in narrowing genioplasty. PMID- 26893980 TI - Asian Breast Augmentation: A Systematic Review. AB - BACKGROUND: Economic, cultural, and regulatory phenomena may explain recent popularization of implant-based augmentation in Asia; but the collective Eastern experience remains limited. Asian surgeons and their patients rely on evidence based medicine that originates elsewhere and may not be entirely relevant. Distinct anatomic and cultural features of Asian women warrant a tailored approach to breast augmentation. We explore the Asian experience with a thorough exploration of the recent literature. METHODS: A literature search was performed for articles written after 2000, of Asian women who underwent augmentation mammoplasty using MEDLINE, Embase, and Pubmed Databases. Technique and outcomes data were summarized. RESULTS: Twelve articles reported outcomes of 2089 women. Korea contributed most series (English language, 7), followed by China (3), Taiwan (1), and Japan (1). Silicone implants were used in 82.1% of women studied, and almost exclusively after 2009. More round (68.9%) than anatomic implants (31.1%) were placed. Non-inframammary (axillary, areolar, and umbilical) incisions were used in 96.9% of cases. Nearly all implants were positioned below the muscle or fascia; subglandular placement accounted for 1.1% of cases. Implant/nipple malposition (1.3%), capsular contracture (1.9%), hematoma (0.6%), and infection (0.2%) rates were reported in most series. Undesirable scarring was the most frequent complication (7.3%), but was reported only in 4 of 12 series. CONCLUSIONS: Studies of Asian women undergoing augmentation mammoplasty are limited, often with ill-defined outcomes and inadequate follow-up. As experience accumulates, an expanding literature relevant to Asian women will provide evidence-based guidelines that improve outcomes and patient satisfaction, and foster innovation. PMID- 26893981 TI - Delphi Study Consensus Recommendations: Patient Selection and Preoperative Planning Measurements for Natrelle 410. AB - BACKGROUND: There is considerable variation in the planning and implementation process for breast augmentation. Although general guidelines are available, the distinctive characteristics of the Natrelle 410 breast implant warrant surgical guidelines specific to this device. This study aimed to develop consensus recommendations for patient selection and preoperative planning for Natrelle 410 in primary breast augmentation. METHODS: Surgeons were invited to participate in this study, which used a modified Delphi method. Participants completed 2 rounds of online surveys, with the second round (Recommendations Survey) based on responses from the first round. Respondents also listed their top priorities for using Natrelle 410 implants. RESULTS: Participants (n = 22) reached consensus on 15 of 18 criteria for patient selection; tuberous breasts, patient preference regarding upper pole shape, and asymmetry of the breasts were the top 3 patient characteristics considered appropriate for the use of Natrelle 410. Consensus was reached on 38 of 51 items related to preoperative planning, with 8 measurements and 6 markings recommended by the participants. Patient-desired outcome was considered the most essential element for Natrelle 410 implant selection; quality of skin envelope and height and width dimension of the breast were selected as the most essential elements for Natrelle 410 implant volume selection. CONCLUSIONS: The modified Delphi method resulted in consensus recommendations for patient selection and preoperative planning in primary breast augmentation with the Natrelle 410 breast implant. These recommendations and priorities, used in concert with a surgeon's clinical experience, are designed to optimize surgical outcomes. PMID- 26893982 TI - Delphi Consensus Recommendations: Intraoperative Technique and Postoperative Management of Patients with Natrelle 410 Implants. AB - BACKGROUND: Anatomically shaped, form-stable Natrelle 410 breast implants were approved in Europe in 1993 and in the United States in 2013. Although general guidelines for breast augmentation are available, the distinctive characteristics of Natrelle 410 warrant specific guidelines for this device. The goal of this study was to generate consensus recommendations for intraoperative technique and postoperative management with Natrelle 410 in primary breast augmentation. METHODS: Surgeons were invited to participate in the study, which used a modified Delphi method. Participants completed 2 rounds of online surveys; the second survey (Recommendations Survey) was generated based on first survey results. Respondents also listed top priorities for use of Natrelle 410. RESULTS: Participants (n = 22) reached consensus on 15 of 18 perioperative and surgical techniques; dual-plane placement, tight pockets, and limiting the boundaries of dissection were among intraoperative techniques considered most important for Natrelle 410. Consensus was reached for 18 of 32 items regarding postoperative management and 6 of 9 open-ended postoperative activity restrictions. Consensus on activity restrictions with specified time limits were similar to consensus recommendations on general restrictions. Top participant-identified intraoperative and postoperative management practices for Natrelle 410 were dual plane placement of the implant and wearing a bra postoperatively, respectively. CONCLUSIONS: The Delphi method identified consensus recommendations on a broad range of intraoperative techniques and postoperative management practices for primary breast augmentation with Natrelle 410. These recommendations and priorities provide surgeons with a framework that, together with the surgeon's experience, will contribute to optimal clinical outcomes with Natrelle 410. PMID- 26893983 TI - Reconstruction of Chopart's Amputation Stump Using Artificial Dermis Combined with Free Anterolateral Thigh Flap. AB - A 63-year-old man dropped a metal chunk onto his left foot during his work and suffered a crush injury of the left forefoot. He underwent Chopart's amputation followed by stump coverage with sole skin at the orthopedic department on the same day. He was referred to our department for reconstruction because of poor vascularization and subsequent necrosis of tissue at the stump. After the necrotic tissue was debrided, exposure of the talus bone was noted. An artificial dermis was then applied to the stump wound, followed by local negative pressure wound therapy. After 3 weeks, the generation of a strong dermis-like tissue was observed at the site of artificial dermis grafting. We then performed flow through free anterolateral thigh flap grafting to reconstruct the stump wound. This procedure involved suturing of the peroneal muscle group and tibialis anterior muscle, which were cut off during Chopart's amputation, and suturing the soft tissue surrounding the calcaneus firmly to the fascia lata of the anterolateral thigh flap, followed by suturing of the flap to the skin defect of the left foot. There were neither postoperative complications, such as skin ulcer and equinus/varus deformity, nor need for secondary repair of the grafted flap, so the patient was able to smoothly enter a rehabilitation program including gait training. The current reconstruction technique for the tissue defect following Chopart's amputation, consisting of artificial dermis grafting, negative pressure wound therapy, and flow-through free anterolateral thigh flap grafting, enabled safe and smooth gait rehabilitation with a forefoot prosthesis. PMID- 26893984 TI - Total Columella Reconstruction Using Nasocheek Flap and Septal Cartilage Graft. AB - The use of the nasocheek sulcus flap with a cartilage strut provides an aesthetically pleasing result in total columella reconstruction. This provides thin hairless skin appropriate for the subunit. Mohs surgery aids in limiting the excision to the tumor involved area, providing a complete clearance and conserving precious units, which have an impact on the reconstructive options. The method of reconstruction described here is simple and easily reproducible, providing an optimal result with almost no donor site morbidity. PMID- 26893985 TI - Pediatric Stinger Syndrome: Acute Brachial Plexopathy After Minor Trauma. AB - The "stinger" or "burner" is a form of transient brachial plexopathy termed for its characteristic knife-like pain extending from the neck to the fingertips. Muscle weakness and paresthesia are oftentimes associated symptoms and are similarly temporary. Commonly observed in athletes of contact sports, the stinger results from high force trauma causing either traction/direct compression to the brachial plexus or extension/compression of the cervical nerve roots. We describe a pediatric case of a stinger in a 14-year-old boy, which was caused by a relatively low force trauma accident. Our management strategy and recommendations are discussed. PMID- 26893986 TI - Persistent Pain and Sensory Abnormalities after Abdominoplasty. AB - BACKGROUND: Persistent postsurgical pain is a well-recognized problem after a number of common surgical procedures, such as amputation, thoracotomy, and inguinal hernia repair. Less is known about persistent pain after cosmetic surgical procedures. We, therefore, decided to study the incidence and characteristics of persistent pain after abdominoplasty, which is one of the most frequent cosmetic surgical procedures. METHODS: In September 2014, a link to a web-based questionnaire was mailed to 217 patients who had undergone abdominoplasty between 2006 and 2014 at the Department of Plastic Surgery, Aalborg University Hospital, Denmark. The questionnaire included questions about pain and sensory abnormalities located to the abdominal skin, and physical and psychological function; patient satisfaction with surgery was rated on a 4-point scale. RESULTS: One hundred seventy patients answered the questionnaire. Fourteen patients (8.2%) reported pain within the past 7 days related to the abdominoplasty. Abnormal abdominal skin sensation was common and reported by 138 patients (81%). Sensory hypersensitivity was associated with the presence of persistent pain. Satisfaction with the procedure was reported by 149 (88%) patients. The majority of patients reported improvement on all physical and psychological factors. Patients with pain were more often disappointed with the surgery and unwilling to recommend the surgery. CONCLUSIONS: Overall, patients were satisfied with the procedure, although abnormal abdominal skin sensation was common. However, there is a risk of developing persistent neuropathic pain after abdominoplasty, and patients should be informed about this before surgery. PMID- 26893987 TI - LED Light Characteristics for Surgical Shadowless Lamps and Surgical Loupes. AB - BACKGROUND: Blue light has more energy than longer wavelength light and can penetrate the eye to reach the retina. When surgeons use magnifying loupes under intensive surgical shadowless lamps for better view of the surgical field, the total luminance is about 200 times brighter than that of typical office lighting. In this study, the effects of 2 types of shadowless lamps were compared. Moreover, the effect of various eyeglasses, which support magnifying loupes, on both the light energy and color rendering was considered. METHODS: The light intensity and color rendering were measured on 3 variables: light transmittance, light intensity, and color rendering. RESULTS: Under shadowless lamps, the light energy increased with low-magnification loupes and decreased with high magnification loupes. Filtering eyeglasses reduced the energy, especially in conditions where the low-magnification loupe was used. The best color-rendering index values were obtained with computer eyeglasses under conventional light emitting diode shadowless lamps and with no glass and with lightly yellow-tinted lenses under less-blue light-emitting diode. CONCLUSIONS: Microsurgeons are exposed to strong lighting throughout their career, and proper color rendering must be considered for easier recognition. Light toxicity and loss of color rendering can be reduced with an appropriate combination of shadowless lamps and colored eyeglasses. PMID- 26893988 TI - Tissue Expanders in Skin Deficient Ventral Hernias Utilizing Component Separation. AB - Skin deficient complex ventral hernias are complicated surgical cases that have multimodal approaches. There is no current consensus on the management of those patients who also have concomitant stomas or enterocutaneous fistula. We present 2 cases in which the senior authors were able to apply tissue expanders above and between the abdominal wall in patients with an enterocutaneous fistula or stoma. After expansion and final closure, the patients did not experience recurrent hernias. PMID- 26893989 TI - The Role of Muscle Flaps for Salvage of Failed Perforator Free Flaps. AB - BACKGROUND: Despite the most heroic efforts, sometimes free flaps fail. Perforator free flaps are not invincible and can suffer the same fate. The real challenge is how to decide what is the next best choice for achieving the desired outcome. METHODS: Over the past decade, 298 free perforator flaps were used in our institution. Total failure occurred in 16 patients, and partial failure requiring a second free flap occurred in an additional 6 patients for a true success rate of 93%. All failures had some form of secondary vascularized tissue transfer, which included the use of muscle flaps in 9 (41%) different patients. RESULTS: Initial flap salvage after a failed perforator free flap was attempted with 12 perforator and 5 muscle free flaps as well as 1 perforator and 2 muscle local flaps. These were not all successful, with loss of 3 muscle free flaps and 3 perforator flaps. Tertiary free flap coverage was successful in 3 cases using 2 muscle flaps and 1 perforator free flap. Local fasciocutaneous flaps or primary wound closure was used in the remaining individuals. CONCLUSIONS: Microsurgical tissue transfers can be the most rewarding and at the same time the most challenging reconstructive endeavor. Persistence in achieving the desired outcome can require multiple steps. Perforator flaps are an important asset to obtain this goal. However, muscle flaps can still be a useful alternative, and the message is that they should not be overlooked as sometimes a viable option. PMID- 26893990 TI - Costal Grafting in Mandibular Reconstruction. AB - BACKGROUND: Reconstruction of mandibular bone defect is a common indication in craniomaxillofacial surgery, and free fibular flap is the gold standard for this indication. However, there are alternatives; nonvascular bone grafting is one of them, and we present the costal grafting for mandibular reconstruction, a classic technique that is reliable, efficient, and produced less morbidity than the technique of using composite free flaps. METHOD: A 9-year retrospective review of 54 patients treated surgically for mandibular reconstruction was performed. The criterion mainly analyzed was graft survival. The surgical technique was described in detail. RESULTS: A total of 54 patients with mandibular bone defect were identified. Five symphysis, 46 corpus, and 20 ramus defects were considered. These patients underwent reconstruction by costal grafting, and the engrafting was successful in 92.6% of cases. Dental rehabilitation with dental implants was realized in 70% of cases. CONCLUSIONS: The approach described in this article allowed the authors to obtain good results with costal grafting for mandibular reconstruction and dental rehabilitation. Costal grafting is a good alternative for fibula free flap in specific indications. Reconstruction of mandibular bone defect is a common indication in craniomaxillofacial surgery. Since the 1980s, the gold standard for these defects is the use of free fibular flap.(1) In some cases, this technique is contradicted; the surgeon then has several possibilities for the use of free osteomyocutaneous flaps (iliac crest, scapula, and serrato costal flaps).(2-8). PMID- 26893992 TI - Perpendicular Strut Injection of Hyaluronic Acid Filler for Deep Wrinkles. AB - Although various injection techniques of hyaluronic acid (HA) filler for facial rejuvenation have been developed, correction of deep wrinkles/grooves, such as the nasolabial fold (NLF), with intradermal or subdermal injections remains difficult. We tested the intradermal HA injection method to place multiple HA struts by (1) inserting a small needle perpendicularly to the wrinkle and (2) injecting HA as intradermal struts with the skin fully stretched by the practitioner's fingers. The results of both NLFs in 10 patients suggest that this technique improves NLFs and maintain the effects more consistently than conventional techniques, although the effects of both methods were almost lost after 6 months. Selective and/or combined application of this technique may enhance the current approach to facial rejuvenation with dermal fillers. PMID- 26893991 TI - Cost-Utility Analysis: Sartorius Flap versus Negative Pressure Therapy for Infected Vascular Groin Graft Managment. AB - BACKGROUND: Sartorius flap coverage and adjunctive negative pressure wound therapy (NPWT) have been described in managing infected vascular groin grafts with varying cost and clinical success. We performed a cost-utility analysis comparing sartorius flap with NPWT in managing an infected vascular groin graft. METHODS: A literature review compiling outcomes for sartorius flap and NPWT interventions was conducted from peer-reviewed journals in MEDLINE (PubMed) and EMBASE. Utility scores were derived from expert opinion and used to estimate quality-adjusted life years (QALYs). Medicare current procedure terminology and diagnosis-related groups codes were used to assess the costs for successful graft salvage with the associated complications. Incremental cost-effectiveness was assessed at $50,000/QALY, and both univariate and probabilistic sensitivity analyses were conducted to assess robustness of the conclusions. RESULTS: Thirty two studies were used pooling 384 patients (234 sartorius flaps and 150 NPWT). NPWT had better clinical outcomes (86.7% success rate, 0.9% minor complication rate, and 13.3% major complication rate) than sartorius flap (81.6% success rate, 8.0% minor complication rate, and 18.4% major complication rate). NPWT was less costly ($12,366 versus $23,516) and slightly more effective (12.06 QALY versus 12.05 QALY) compared with sartorius flap. Sensitivity analyses confirmed the robustness of the base case findings; NPWT was either cost-effective at $50,000/QALY or dominated sartorius flap in 81.6% of all probabilistic sensitivity analyses. CONCLUSION: In our cost-utility analysis, use of adjunctive NPWT, along with debridement and antibiotic treatment, for managing infected vascular groin graft wounds was found to be a more cost-effective option when compared with sartorius flaps. PMID- 26893993 TI - Forequarter Amputation and Immediate Reconstruction with a Free Extended Humeral Radial Forearm Flap. AB - A forequarter amputation is a radical ablative surgical procedure that includes the entire upper extremity with its shoulder girdle. We present a 53-year-old woman with a solid slow growing tumor in her right shoulder of 15 x 20 cm in diameter. Resection and immediate reconstruction with a free radial forearm flap extended from the distal third of the arm to the midpalmar region, taking the humeral artery and the cephalic vein as a main peddicle. The final outcome is shown at six weeks after the surgery. PMID- 26893994 TI - Incidence of Seromas and Infections Using Fenestrated versus Nonfenestrated Acellular Dermal Matrix in Breast Reconstructions. AB - BACKGROUND: Acellular dermal matrices (ADMs) provide clinical benefits in breast reconstruction but have been associated with increased postoperative complications, most frequently seromas. Fenestration of the ADM before insertion into the reconstructed breast may reduce the incidence of postoperative complications. In this retrospective analysis, postoperative complications were assessed after breast reconstruction with or without fenestrated ADMs. METHODS: Patients who underwent immediate 2-staged implant breast reconstructions using ADM at a single center were assessed. The number of reconstructed breasts was stratified by ADM fenestration status and ADM type. The incidence of seroma, infection, extrusion, and explantation, and cosmetic score, was compared within the 2 stratified groups. A multivariable regression was performed to identify independent risk factors associated with these complications and aesthetic outcome. RESULTS: In total, data from 450 patients who had 603 breast reconstructions using either AlloDerm or FlexHD demonstrated a significantly higher incidence of seroma with nonfenestrated ADMs (20%) versus fenestrated ADMs (11%; P = 0.0098). Rates of infection and explantation, and cosmetic score, were not influenced by fenestration status. In the multivariable analysis, ADM fenestration remained a significant protective factor for seroma formation. FlexHD also yielded a lower incidence of extrusion (P = 0.0031) and a higher cosmetic score (P = 0.0466) compared with AlloDerm after adjusting for other risk factors. CONCLUSIONS: The results of this study support ADM fenestration for reduction of seroma incidence in breast reconstruction, without affecting cosmetic results. Additionally, the choice of ADM may reduce extrusion incidence and improve aesthetic outcomes. PMID- 26893995 TI - Evaluation of the Effects of Bile on the Arterial Tonus in a Rabbit Model. AB - BACKGROUND: Hepatic artery anastomosis is an essential part of live-donor liver transplantation, and during this anastomosis, an unusual contact between bile and vessel ends is observed. In this study, the effects of this nonphysiological contact in a rabbit model were evaluated. METHODS: The study was designed in 2 steps-in vitro and in vivo. Three groups were established for the in vitro study. In the first group, vessels were incubated in Krebs solution with 5% bile for 1 minute. In the second group, vessels were kept in Krebs solution with 5% bile for 5 minutes. Vessels in the control group were kept in Krebs solution without bile. All groups were examined for responses to vasodilator and vasoconstrictor agents in organ bath system. The specimens were evaluated immunohistochemically and histopathologically. In the in vivo step, microvascular anastomosis was performed bilaterally. Right carotid artery was anastomosed during bile contamination as study group, and left carotid artery was anastomosed without bile contamination as control group. Blood flow indexes were measured. RESULTS: The results of the in vitro study revealed decreased responses to contractile and relaxing agents in the first study group compared with that of the control group (P < 0.0001). There was no response obtained in the second study group. The Doppler ultrasound results revealed no difference between preoperative and postoperative flow indexes (P > 0.05). There was no postoperative spasm in the study group. However, there was significant vasospasm in the control group (P < 0.05). CONCLUSIONS: Vessels exposed to bile have decreased contractile and relaxing responses, and this effect increases with exposure duration. PMID- 26893996 TI - Denying the Obvious: Four Extreme Cases of Neglected Tumors. AB - BACKGROUND: Little is known about the relatively common phenomenon of patients neglecting tumors as part of a denial mechanism to presumably cope with the obvious, outward and clearly visible signs of cancer. As a result of this tumor neglect, disease progression continues unchecked, resulting in excessive tumor growth, invasion of nearby structures, (often) metastatic spread, and significant disfigurement. METHODS: In this case series, we present 4 extreme cases of neglected tumors that posed significant reconstructive challenges and explore the biopsychosocial components of tumor neglect. RESULTS: In this series, we present 4 cases representing various cases of extreme tumor neglect. These 4 cases required multidisciplinary efforts involved in tumor resection, adjuvant treatments and the complex reconstructive efforts after tumor extirpation. CONCLUSIONS: The tumor neglect phenomenon is of broad interest to the field of plastic and reconstructive surgery. Given the complex patient factors that contribute to the extreme state of disease progress upon presentation, all cases required extensive extirpative efforts with complex and challenging reconstructive solutions. Cases of extreme tumor neglect provide insight into the biopsychosocial underpinnings of this specific patient population and have implications for a further understanding of the potential immunoprotective effect of these large, longstanding, and often nonmetastatic tumors. PMID- 26893997 TI - Open-book Splitting of a Distally Based Peroneus Brevis Muscle Flap to Cover Large Leg and Ankle Defects. AB - Large soft-tissue defects in the lower leg and ankle are a major problem for plastic surgeons. Many local flaps that are either proximally or distally based have been previously described to cover small defects. Larger defects may require a distant flap that is either pedicled or free. The peroneus brevis muscle flap is a well-known distally based safe flap that is used to cover a small defect. METHODS: Ten distally based peroneus brevis muscle flaps were elevated in 10 patients (8 males and 2 females) with major lower third leg and ankle defects that were 6-12 cm in length and 6-10 cm in width, with open-book splitting of the proximal portion of the muscle to cover these large defects. RESULTS: Flap survival was excellent, and partial skin graft loss in two cases healed with dressing. The average flap length was 10 cm, ranging between 6 and 12 cm. The average flap width was 8 cm, ranging between 6 and 10 cm. The donor site also healed uneventful. CONCLUSIONS: Open-book splitting of the distally based peroneus brevis muscle flap is ideally suited for moderate to large defects in the distal third of the lower leg and ankle. This modification of the distally based peroneus brevis muscle flap offers a convincing alternative for covering large defects of up to 12 * 10 cm in the distal leg and ankle region. PMID- 26893998 TI - Response to Video Capture of Plastic Surgery Procedures Using the GoPro HERO 3+: Patient Privacy and Compliance. AB - Supplemental Digital Content is available in the text. PMID- 26894000 TI - Safety and Efficacy of Stabilized Hyaluronic Acid Gel for Breast Enhancement. AB - Long-term follow-up data following 2 breast enhancement treatments with stabilized hyaluronic acid (HA) gel are limited. Although HA gel is no longer marketed for breast enhancement, there is a clinical need for information about follow-up of previously treated women. A multicenter, noncomparative study was conducted in women seeking breast enhancement. Subjects received 1 treatment of HA gel (maximum, 100 mL/breast); a subgroup underwent retreatment 9 months later. Follow-up was conducted for 24 months after last treatment; endpoints included magnetic resonance imaging for estimation of gel degradation, adverse events, breast examinations, Global Esthetic Improvement Scale, and satisfaction ratings. Seventy-one subjects received 1 treatment, with 22 (31%) receiving retreatment after 9 months. Twenty-four months after last treatment, the mean percentage of remaining gel was 17% in the single-treatment group and 21% in the retreatment group; complete degradation had not occurred in any subject. The most commonly reported treatment-related adverse events were implant-site nodules, medical device implantation events, capsular contracture associated with breast implant, and injection-site nodules; most were mild to moderate and required no intervention. Based on subject Global Esthetic Improvement Scale ratings, 36% of breasts in the single- treatment group and 50% of breasts in the retreatment group were improved 24 months after last treatment, but subject satisfaction had returned to baseline levels. Some gel remained in all subjects 24 months after last treatment. Although single treatment and retreatment were generally well tolerated, physicians need to be aware of common treatment-related complications to manage them adequately. PMID- 26893999 TI - Subcutaneous Direct-to-Implant Breast Reconstruction: Surgical, Functional, and Aesthetic Results after Long-Term Follow-Up. AB - Direct-to-implant breast reconstruction can be achieved more easily by means of soft-tissue replacement devices such as dermal matrices and synthetic meshes. The feasibility of a subcutaneous approach has been recently investigated by some studies with different devices functioning as implant support. Aim of this study is to analyze the long-term results, both objective and subjective, of a previous nonrandomized trial comparing prepectoral (subcutaneous) and retropectoral breast reconstructions. METHODS: Patients enrolled in a nonrandomized prospective trial, comparing the standard retropectoral reconstruction and the prepectoral subcutaneous approach, using a titanium-coated mesh in both techniques, were followed up and evaluated for long-term results. Cases were compared in terms of the causes and rate of reinterventions, of the postoperative BREAST-Q questionnaire results, and of an objective surgical evaluation. RESULTS: The subcutaneous group had a rate of implant failure and removal of 5.1% when compared with 0% in the retropectoral group. Aesthetic outcome was significantly better for the subcutaneous group both at a subjective and at an objective evaluation. Capsular contracture rate was 0% in the subcutaneous group. CONCLUSIONS: A higher rate of implant failure and removal, although not significant, always because of skin flaps and wound problems, should be taken into account for a careful patients selection. The subcutaneous breast reconstruction shows good long-term results. A coherent subjective and objective cosmetic advantage of this approach emerges. Moreover, no capsular contracture is evident, albeit in a relatively limited number of cases. PMID- 26894001 TI - Technical Improvements to a Rat Brachial Plexus Avulsion Model via a Posterior Surgical Approach. AB - Supplemental Digital Content is available in the text. PMID- 26894002 TI - Subcutaneous Tissue Expander Placement with Synthetic Titanium-Coated Mesh in Breast Reconstruction: Long-term Results. AB - A subcutaneous, prepectoral, muscle-sparing approach has been recently described for implant-based breast reconstruction. This is a preliminary series of 2-stage breast reconstructions by means of tissue expander placed subcutaneously with the support of a titanium-coated polypropylene mesh. A pilot series of cases was started in 2012. Inclusion criteria were informed consent, age less than 80 years, normal body mass index (range, 18.5-24.9), no T4 and metastatic cancers, no comorbidities, and nonsmoking patients. Expander losses, infections, seromas, skin/nipple necrosis, wound dehiscence, and reinterventions were registered in follow-up visits. Furthermore, patients were followed up in second-stage procedures and for at least 1 year from implant positioning to collect any surgical complication, reinterventions, cosmetic outcome, and oncological data. Between June 2012 and March 2014, 25 cases were enrolled in the study. Expander/implant loss rate was 0%. Skin/nipple necrosis rate was 4%. Infections rate was 12% after first-stage and 4% after second-stage procedure. Seromas rate was 0%. Five (20%) fat graft procedures were performed over the expander before second-stage reconstruction, and no reinterventions were required after second stage. Patients mean score was 99 for cosmetic outcome satisfaction, in a 0-100 scale. Subcutaneous 2-stage reconstruction with synthetic mesh proved safe and feasible. Patients satisfaction is very good after 14 months median follow-up form definitive implant placement. Although the present study involved only a small number of cases, a tissue-expander subcutaneous reconstruction seems to have promising results. Whenever pectoralis major muscle can be spared, a conservative reconstruction might be an option. PMID- 26894003 TI - Mechanobiology and Mechanotherapy of Adipose Tissue-Effect of Mechanical Force on Fat Tissue Engineering. AB - Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat. PMID- 26894004 TI - A Subglandular Breast Cerebrospinal Fluid Pseudocyst Following Postsurgical Shunt Migration. AB - Cerebrospinal fluid (CSF) drainage catheters have been associated with numerous complications in various anatomic locations, because of migration, infection, and obstruction. However, breast-related CSF shunt complications tend to occur infrequently or have seldom been reported in the empirical literature. Therefore, a case is presented detailing a breast pseudocyst caused by migration and subsequent coiling of a ventriculoperitoneal shunt in the right breast pocket. To the best of the authors' knowledge, this is the first case that has been reported in the peer-reviewed literature of a pseudocyst resulting from a CSF drainage catheter coiling around the breast implant post pancreaticoduodenectomy. Moreover, this case highlights the importance of cross-disciplinary procedural awareness, particularly in regards to breast, ventriculoperitoneal shunt, and pancreatic procedures. PMID- 26894005 TI - Chronic Sclerosing Osteomyelitis of the Mandible Treated with Hemimandibulectomy and Fibular Free Flap Reconstruction. AB - Primary chronic osteomyelitis of the mandible is a rare condition that presents with a long-standing chronic facial swelling over the mandible, pain with mastication, and trismus. With no clinically appreciated acute phase, the aetiology often remains unknown. Many patients achieve adequate symptom control with broad-spectrum antibiotics, hyperbaric oxygen therapy and surgical debridement, or decortication of bone sequestration. However, because of the rarity of primary chronic osteomyelitis and the extensive involvement of the mandible that can result, we present a case of a 32-year-old woman with chronic disease of the left mandible requiring a left hemimandibulectomy and fibular free flap reconstruction. Few such cases have been reported in the literature, which require such extensive resection and reconstruction to control long-standing symptoms. PMID- 26894006 TI - Infection in the Nasal Tip Caused by Acellular Dermal Matrix. AB - A 19-year-old female patient visited our clinic for rhinoplasty. She complained about her low take-off point, which was apparent in profile view, and wanted slight tip projection. She refused additional cartilage harvesting from ears or ribs but consented to the use of homologous tissue, including acellular dermal matrix, for her dorsum and tip. Septoturbinoplasty was performed, and only a very small amount of septal cartilage could be harvested. It was used as both the columellar strut and the alar rim graft. Nasal dorsum and tip were augmented with acellular dermal matrix. Three months postoperatively, she experienced a few episodes of edema and redness on her nasal tip, followed by pus exudation from the nasal skin. Six months postoperatively, she underwent revision rhinoplasty for removal of inflamed grafts, and onlay tip graft with homologous rib cartilage was performed. Nasal dorsum or tip grafts are an integral part of Asian rhinoplasty. Autogenous tissue is the gold standard for grafting materials. However, the limited availability of autogenous tissue and the preference of patients and surgeons for artificial surgical implants make Asian rhinoplasty challenging. Unavailability of autogenous cartilage and patient refusal of artificial implants led to the use of acellular dermal matrix (ADM) in the nasal dorsum and tip for this case. This is the first report of postoperative complication because of infection rather than absorption after ADM use. PMID- 26894007 TI - The Role of Embryologic Fusion Planes in the Invasiveness and Recurrence of Basal Cell Carcinoma: A Classic Mix-Up of Causation and Correlation. AB - The facial embryologic fusion planes as regions of mesenchymal and ectodermal fusion of the primordial facial processes during embryological development have been suggested to influence the spread, invasiveness, pathogenesis, and recurrence of cutaneous carcinoma. This study sought to establish whether basal cell carcinoma (BCC) originating in embryologic fusion planes has a greater propensity for earlier depth of invasion, leading to an increased rate of lesion recurrence. METHODS: Facial BCCs excised in a single surgeon practice over 2 years were allocated into 2 anatomic domains according to their correlation with embryologic fusion planes. Lesion depth of invasion, surface area, and margins of excision were analyzed in conjunction with recurrence data over the following 70 80 months. RESULTS: Of the 331 lesions examined, 70 were located in embryologic fusion planes. No difference was found in the mean surface area and depth of invasion for lesions located in the 2 domains (P > 0.05). Ten lesion recurrences were identified, none of which were located in embryologic fusion planes. Recurrent lesions were excised with a significantly greater percentage of close and incomplete excision margins (P < 0.05). CONCLUSIONS: BCC arising in embryologic fusion planes are not more invasive or at greater risk of recurrence. Excision margins seem to have the greatest influence on lesion recurrence. Because of the paucity of superfluous tissue and the cosmetic and functionally sensitive nature of these areas of embryologic fusion, specialist treatment of these lesions is recommended to ensure that adequacy of excision is not neglected at the cost of ease of closure and cosmesis. PMID- 26894008 TI - A Multisite Study of Oral Clefts and Associated Abnormalities in Thailand: The Epidemiologic Data. AB - This study aimed to obtain epidemiological data of birth incidences of cleft lips and/or cleft palates (CLP) in the Thai population with associated risk factors. METHODS: The data were collected for a period of 12 months between 2003 and 2004 for infants' deliveries with CLP and associated risk factors in all hospitals of 6 provinces from 4 regions of Thailand. The birth incidence, related factors with cleft birth, and linkage with geographical area were analyzed by the geographic information system. RESULTS: Phitsanulok, Saraburi, and Khon Kaen had higher birth incidences for CLP of 2.01, 1.69, and 1.66 per 1000 live births, respectively, and the overall birth incidence was 1.51 per 1000 live births. There were a total of 112 cleft births (61 males and 51 females) with 43 cleft lips, 18 cleft palates, and 51 cleft lips + cleft palates. The northeast region had infants with different gestational ages at birth and mothers with higher intakes of vitamins and a use of vitamin A supplement or retinoic acid than others. A use of folic acid supplement was low in all 4 regions. CONCLUSIONS: The varied incidence of CLP may reflect the incomplete accuracy of case ascertainment. A number of challenges were addressed. The geographic information system was helpful for more background investigation and planning of cleft care management. Our study enables future studies of etiological factors and future birth registries. PMID- 26894009 TI - Free Pulp Transfer for Fingertip Reconstruction-The Algorithm for Complicated Allen Fingertip Defect. AB - We present a review of all the cases of free toe pulp transfer and an algorithm for application of free pulp transfer in complicated Allen fingertip defect. METHODS: Seventeen patients underwent free toe pulp transfer for fingertip reconstruction by the senior author. Twelve cases were Allen type II with oblique pulp defect, 4 were Allen type III, and 1 patient had 2 fingertip injuries classified both as type IV. According to the algorithm presented, for the type III defects where the germinal matrix is still preserved, we use free pulp transfer and nail bed graft to preserve the nail growth instead of toe to hand transfer. For the type IV injuries with multiple defects, a combination of web flap from both big toe and second toe is possible for 1-stage reconstruction. RESULTS: All pulp flaps survived completely. Static 2-point discrimination ranged from 6 to 15 mm (mean: 10.5 mm). No patient presented dysesthesia, hyperesthesia, pain at rest, or cold intolerance. The donor site did not present any nuisances apart from partial skin graft loss in 3 cases. CONCLUSIONS: We tried to classify and modify the defects' reconstruction according to Allen classification. Free toe pulp transfer is a "like with like" reconstruction that provides sensate, glabrous skin with good color and texture match for fingertip trauma, and minimal donor site morbidity compared with traditional toe to hand transfer. PMID- 26894011 TI - Primary Squamous Cell Carcinoma Arising from a Breast Implant Capsule. AB - Primary squamous cell carcinoma (SCC) of the breast comprises less than 0.1% of all breast cancers. Literature review reveals only 1 reported case of an SCC arising from the capsule of a breast implant. The authors describe, herein, a primary SCC arising from the capsule of a long-standing silicone breast implant. PMID- 26894010 TI - A Prospective Study Assessing Complication Rates and Patient-Reported Outcomes in Breast Reconstructions Using a Novel, Deep Dermal Human Acellular Dermal Matrix. AB - The value proposition of an acellular dermal matrix (ADM) taken from the deep dermis is that the allograft may be more porous, allowing for enhanced integration and revascularization. In turn, this characteristic may attenuate complications related to foreign body reactions, seromas, and infection. However, this is juxtaposed against the potential loss of allograft structural integrity, with subsequent risk of malposition and extrusion. Despite the active use of novel, deep dermal ADMs, the clinical outcomes of this new technology has not been well studied. METHODS: This is a prospective study to evaluate surgical and patient-reported outcomes using a deep dermal ADM, FlexHD Pliable. Surgical outcomes and BREAST-Q patient-reported outcomes were evaluated postoperatively at 2- and 6-month time points. RESULTS: Seventy-two breasts (41 patients) underwent reconstruction. Complication rate was 12.5%, including 2 hematomas and 7 flap necroses. One case of flap necrosis led to reconstructive failure. Notably, there were no cases of infection, seroma, or implant extrusion or malposition. Average BREAST-Q scores were satisfaction with outcome (70.13 +/- 23.87), satisfaction with breasts (58.53 +/- 20.00), psychosocial well being (67.97 +/- 20.93), sexual well being (54.11 +/- 27.72), and physical well being (70.45 +/- 15.44). Two month postoperative BREAST-Q scores decreased compared with baseline and returned to baseline by 6 months. Postoperative radiation therapy had a negative effect on satisfaction with breasts (P = 0.004) and sexual well being (P = 0.006). CONCLUSIONS: Deep dermal ADM is a novel modification of traditional allograft technology. Use of the deep dermal ADM yielded acceptably low complication rates and satisfactory patient-reported outcomes. PMID- 26894012 TI - Total Single-Stage Autologous Breast Reconstruction with Free Nipple Grafts. AB - Outstanding results are difficult to achieve in postmastectomy reconstructions in obese ptotic patients. We describe an autologous single-stage reconstruction with free nipple grafts that is best suited for these difficult patients. This technique allows for delayed volume supplementation with implants or fat grafting but does not commit the patient to additional surgery. It avoids the common complications of immediate implant-based reconstructions. This technique is also an excellent option in patients with a known requirement for radiotherapy as it does not sacrifice a valuable autologous flap nor does it subject the patient to capsular contracture, infection, and extrusion. It also obviates the psychological trauma that many women suffer awaiting a reconstruction after radiotherapy. We believe it should be considered as a first-line reconstructive option. PMID- 26894013 TI - Microvascular Staged Phalloplasty Preserving Original Glans in a Severe Hypospadias: A Case Report. AB - Penile reconstruction is usually performed in patients with gender dysphoria; with penile loss because of trauma, infection, and tumors; and with congenital deformities like severe hypospadias, in which standard techniques do not achieve a good result. Hypospadias are one of the most common inherent genital anomalies in boys. Many surgical procedures have been published for total phallic reconstruction aiming at a functionally and aesthetically pleasing. We present a case of reconstruction of the penis in a severe hypospadias in a 40-year-old man by transferring the original glans to the forearm flap and a stiffening procedure with an osteocutaneous fibular flap 3 months after first surgery. Three months postoperatively, the final result was an acceptable sexual intercourse, normal voiding, and quite normal appearance. Microvascular staged phalloplasty preserving original glans in a severe hypospadia could be considered a surgical option for micropenis. Technical difficulties and microsurgical advanced skills are the main drawback of this approach. PMID- 26894014 TI - Novel Principles and Techniques to Create a Natural Design in Female Hairline Correction Surgery. AB - Female hairline correction surgery is becoming increasingly popular. However, no guidelines or methods of female hairline design have been introduced to date. METHODS: The purpose of this study was to create an initial framework based on the novel principles of female hairline design and then use artistic ability and experience to fine tune this framework. An understanding of the concept of 5 areas (frontal area, frontotemporal recess area, temporal peak, infratemple area, and sideburns) and 5 points (C, A, B, T, and S) is required for female hairline correction surgery (the 5A5P principle). The general concepts of female hairline correction surgery and natural design methods are, herein, explained with a focus on the correlations between these 5 areas and 5 points. RESULTS: A natural and aesthetic female hairline can be created with application of the above-mentioned concepts. CONCLUSION: The 5A5P principle of forming the female hairline is very useful in female hairline correction surgery. PMID- 26894015 TI - Conservative Management of Wound Dehiscence Following Pediatric Cavus Foot Surgery: A Case Series. AB - Cavus foot surgeries are relatively common procedures in pediatric orthopedics. Following surgery, the tensile forces exerted on the wound by the newly corrected foot may hinder soft tissue healing and lead to wound dehiscence. Treatments including skin grafting and other plastic surgery procedures have been described in order to manage this complication. However, the effectiveness of conservative treatment regimens in cases of large dehiscence of these wounds has not yet been reported. METHODS: The charts of 7 patients between the ages of 7 and 19 who had surgical correction of severe cavus deformity and who developed wound dehiscence postoperatively were reviewed. All patients were treated conservatively with regular cleaning with chlorhexedine and application of different ointments and dressings along with surgical debridements. Three patients also received antibiotics. The primary outcome was wound healing as documented by clinical notes and photographs. RESULTS: The treatment was successful in producing the desired outcome in all cases with no other systemic or wound complications developing. Complete wound healing was obtained within a median time of 6 months and 5 days of treatment without the need for skin grafting or other plastic surgery procedures. CONCLUSIONS: In pediatric patients with wound dehiscence postcavus foot surgery, conservative management with minimal surgical debridement and regular cleaning and dressing of the wound is a viable treatment option that has been shown to be effective in 7 cases. It should be considered in such patients before proceeding to more invasive surgical treatment. PMID- 26894017 TI - "Walk the Rim, Feel the Bone" Technique in Superior Sulcus Filling. AB - Superior sulcus filler injection is a nonsurgical method to rejuvenate the upper face. Blindness and stroke are devastating complications of facial filler injection. This study describes an injection technique that minimizes the risk of blindness and includes a case study demonstrating the cosmetic benefits of this procedure. To avoid retrograde injection of filler embolus into the ophthalmic artery, we advocate a "'walk the rim, feel the bone" approach. Small boluses of hyaluronic acid filler are given in preperiosteal plane, avoiding the superior orbital foramen. PMID- 26894016 TI - Hyperspectral Imaging for Burn Depth Assessment in an Animal Model. AB - Differentiating between superficial and deep-dermal (DD) burns remains challenging. Superficial-dermal burns heal with conservative treatment; DD burns often require excision and skin grafting. Decision of surgical treatment is often delayed until burn depth is definitively identified. This study's aim is to assess the ability of hyperspectral imaging (HSI) to differentiate burn depth. METHODS: Thermal injury of graded severity was generated on the dorsum of hairless mice with a heated brass rod. Perfusion and oxygenation parameters of injured skin were measured with HSI, a noninvasive method of diffuse reflectance spectroscopy, at 2 minutes, 1, 24, 48 and 72 hours after wounding. Burn depth was measured histologically in 12 mice from each burn group (n = 72) at 72 hours. RESULTS: Three levels of burn depth were verified histologically: intermediate dermal (ID), DD, and full-thickness. At 24 hours post injury, total hemoglobin (tHb) increased by 67% and 16% in ID and DD burns, respectively. In contrast, tHb decreased to 36% of its original levels in full-thickness burns. Differences in deoxygenated and tHb among all groups were significant (P < 0.001) at 24 hours post injury. CONCLUSIONS: HSI was able to differentiate among 3 discrete levels of burn injury. This is likely because of its correlation with skin perfusion: superficial burn injury causes an inflammatory response and increased perfusion to the burn site, whereas deeper burns destroy the dermal microvasculature and a decrease in perfusion follows. This study supports further investigation of HSI in early burn depth assessment. PMID- 26894018 TI - Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside. AB - Autosomal dominant polycystic kidney disease (ADPKD) is the most common life threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tubular epithelial cells, which plays a crucial role in cyst development and/or growth in PKD. Activation of the proliferative mammalian target of rapamycin (mTOR) signaling pathway has been demonstrated in polycystic kidneys from rodents and humans. mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. On the basis of animal studies, human studies were undertaken. Two large randomized clinical trials published in the New England Journal of Medicine of everolimus or sirolimus in ADPKD patients were very unimpressive and associated with a high side-effect profile. Possible reasons for the unimpressive nature of the human studies include their short duration, the high drop-out rate, suboptimal dosing, lack of randomization of "fast" and "slow progressors" and the lack of correlation between kidney size and kidney function in ADPKD. The future of mTOR inhibition in ADPKD is discussed. PMID- 26894020 TI - Impact of initial blood flow on outcomes of vascular access in hemodialysis patients. AB - BACKGROUND: Direct access flow measurements are considered the most useful surveillance method for significant stenosis, and ultrasound dilution has become the most popular and validated technique. The goal of this study was to evaluate access flow (Qa) at the time of first cannulation and its relationship to the survival of vascular access in Korean hemodialysis patients. METHODS: We conducted a prospective observational study from May 2004 to June 2011. We enrolled 60 patients (36 men) who underwent the first access operation between January 2004 and December 2005 and were followed-up for surveillance. RESULTS: Maturation failure occurred in nine patients (15%). Mean time to first use was 1.8+/-1.2 months after surgery. The patients were followed-up for a mean of 50.5+/-25.9 months. There were 25 deaths and six kidney transplants in patients with a functioning access. The total percutaneous transluminal angioplasty incidence was 50 in 27 patients (0.14/access-year). The initial Qa was 757.5+/ 476.4 mL/minute. First cannulation time was not significantly correlated with initial Qa (r=0.234, P=0.075). A total of 22 of the 60 patients (36.7%) had an initial Qa<500 mL/minute. Maturation failure, initial Qa<500 mL/minute, and the use of antiplatelet agents were risk factors for poor primary patency. Diabetic status and use of a graft were risk factors for low cumulative patency. CONCLUSION: An initial Qa<500 mL/minute is a risk factor for poor primary patency, while an initial Qa<500 mL/minute is not a risk factor for low cumulative patency or mortality. PMID- 26894021 TI - Pharmacokinetics of tacrolimus according to body composition in recipients of kidney transplants. AB - BACKGROUND: Currently, the dosage of tacrolimus used after transplantation is based on the patient's body weight. However, there is a low correlation between body weight and body composition in kidney transplant recipients. In this study, we evaluate the pharmacokinetics of tacrolimus according to body composition in 18 Korean kidney transplant recipients with stable graft function. METHODS: Body composition parameters were calculated using bioelectrical impedance analysis. Pharmacokinetic profiles were determined 0, 1, 2, 3, and 4 hours after treatment with tacrolimus and were compared between high- and low-level median body composition groups. The values of C0, C1, C2, C3, and C4 were used in determining an abbreviated area under the curve (AUC) for tacrolimus. RESULTS: The mean body mass index (BMI) and body composition values were as follows: BMI, 24.3 kg/m(2); lean mass, 49.8 kg; and fat mass, 17.4 kg. There were no statistical differences in pharmacokinetic profiles between groups with different BMIs. However, the C0 and C4 in the high-fat group were significantly elevated compared with those of the low-fat group (P=0.024 and 0.031, respectively). Furthermore, the C0, C2, C3, and C4 and the AUC were significantly different between the two lean mass groups (P=0.007, 0.038, 0.047, 0.015, and 0.015, respectively). Other variables, such as waist circumference and arm muscle circumference, did not differentiate between the pharmacokinetic profiles of tacrolimus. CONCLUSION: Taken together, these data suggest that tacrolimus dose monitoring based on body composition may provide adequate dosage leading to favorable long-term outcomes. PMID- 26894019 TI - Epigenetic modifications and diabetic nephropathy. AB - Diabetic nephropathy (DN) is a major complication associated with both type 1 and type 2 diabetes, and a leading cause of end-stage renal disease. Conventional therapeutic strategies are not fully efficacious in the treatment of DN, suggesting an incomplete understanding of the gene regulation mechanisms involved in its pathogenesis. Furthermore, evidence from clinical trials has demonstrated a "metabolic memory" of prior exposure to hyperglycemia that continues to persist despite subsequent glycemic control. This remains a major challenge in the treatment of DN and other vascular complications. Epigenetic mechanisms such as DNA methylation, nucleosomal histone modifications, and noncoding RNAs control gene expression through regulation of chromatin structure and function and post transcriptional mechanisms without altering the underlying DNA sequence. Emerging evidence indicates that multiple factors involved in the etiology of diabetes can alter epigenetic mechanisms and regulate the susceptibility to diabetes complications. Recent studies have demonstrated the involvement of histone lysine methylation in the regulation of key fibrotic and inflammatory genes related to diabetes complications including DN. Interestingly, histone lysine methylation persisted in vascular cells even after withdrawal from the diabetic milieu, demonstrating a potential role of epigenetic modifications in metabolic memory. Rapid advances in high-throughput technologies in the fields of genomics and epigenomics can lead to the identification of genome-wide alterations in key epigenetic modifications in vascular and renal cells in diabetes. Altogether, these findings can lead to the identification of potential predictive biomarkers and development of novel epigenetic therapies for diabetes and its associated complications. PMID- 26894022 TI - Use of low-dose sulodexide in IgA nephropathy patients on renin-angiotensin system blockades. AB - BACKGROUND: Despite using renin-angiotensin system (RAS) blockades, some of the patients with immunoglobulin A (IgA) nephropathy often had persistent proteinuria of more than 500 mg/d. They need to be managed further by alternative methods to halt the progression of the disease; these methods could also be applied safely over a long period of time. In this context, sulodexide has been studied for the management of diabetic nephropathy. METHODS: A retrospective review was carried out involving 20 patients with IgA nephropathy who had been taking sulodexide (50 mg daily) as an add-on therapy together with an optimal dose of RAS blockades during 2008-2009. We evaluated the proteinuria reduction rates and renal function changes. RESULTS: During 11.1+/-72.7 months of follow-up duration, urinary protein-to-creatinine ratio (UPCR) decreased for 1.57+/-0.6 to 1.17+/-0.7 g/g (P=0.032). Twenty-five percent of the patients showed a greater than 50% reduction of UPCR, and 40% had a UPCR of less than 1.0 g/g at their final observations. The analysis of the factors contributing to the effect found that a higher pretreatment UPCR showed a significant correlation with the UPCR decrease (r=0.45, P=0.047). Neither the adverse effects nor the renal function impairments were documented during the management. CONCLUSION: Low-dose sulodexide has an additional modest antiproteinuric effect on IgA nephropathy undergoing RAS blockade therapy. PMID- 26894023 TI - Clinical characteristics of acute renal failure with severe loin pain and patchy renal vasoconstriction. AB - BACKGROUND: Acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction (PRV) is a syndrome presenting with sudden loin pain after anaerobic exercise. We aimed to investigate the clinical characteristics and the efficacy of diagnostic imaging studies of patients with this syndrome. METHODS: We retrospectively selected 17 patients with ARF accompanied by loin or abdominal pain who showed multiple patchy wedge-shaped delayed contrast enhancements on a computerized tomography scan. Information about the clinical characteristics, including the nature of pain and combined symptoms, suspected causes, such as exercise, drug or alcohol intake, and renal hypouricemia, and the results of laboratory and imaging tests were gathered. RESULTS: The mean age of patients with episodes of ARF accompanied by loin pain was 23.0+/-6.5 (range 16-35) years old. Pain was mainly located in the loin (70.6%) or abdominal area (76.5%) and continued for approximately 3.5+/-4.0 days. Exercise was suspected as a primary cause of disease in 12 (70.6%) patients. Maximal serum creatinine was 5.42+/-3.16 (1.4-12.1) mg/dL 3.1+/-1.8 (1-7) days after the onset of pain. The peak level of serum uric acid was 9.41+/-2.91 (6.0-15.8) mg/dL. All of the patients recovered to near-normal renal function, and one patient showed hypouricemia after recovery. CONCLUSION: ARF with severe loin pain and PRV can present with loin or abdominal pain, even without a history of anaerobic exercise. Careful history taking and appropriate imaging studies are critical in the diagnosis and management of this syndrome. PMID- 26894024 TI - Plasma leptin concentrations are greater in type II diabetic patients and stimulate monocyte chemotactic peptide-1 synthesis via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. AB - BACKGROUND: Leptin is an adipokine that is recently reported to be a biomarker of systemic inflammation. Although atherosclerosis causes cardiovascular diseases, it is not clear whether leptin contributes to the acceleration of this process. In this study, we investigated whether alterations of plasma leptin levels were related to diabetic nephropathy and systemic inflammation. In addition, we examined the physiologic action of leptin in cultured vascular smooth muscle cells (VSMCs). METHODS: A total of 126 type 2 diabetic participants and 37 healthy controls were studied. The diabetic participants were divided into three groups according to stage of nephropathy. We investigated whether leptin induced monocyte chemotactic peptide-1 (MCP-1) synthesis through the mitogen-activated protein kinase (MAPK) pathway using cultured VSMCs. RESULTS: Plasma leptin concentrations were significantly higher in the diabetic group than in the controls. Plasma leptin levels were positively correlated with body mass index, fasting and postprandial blood glucose, hemoglobin A1c, total cholesterol, urinary albumin excretion, high-sensitivity C-reactive protein (hsCRP), and MCP-1 plasma levels, and negatively correlated with creatinine clearance values. In cultured VSMCs, leptin increased MCP-1 production in a dose-dependent manner, and this stimulating effect of leptin on MCP-1 expression was reversed by the MAPK (MEK) inhibitor PD98059. In addition, leptin stimulated the phosphorylation of MEK, extracellular signal-regulated kinase, and E26-like transcription factor, which are components of the MAPK pathway. CONCLUSIONS: Overall, these findings suggest that activation of leptin synthesis may promote MCP-1 activation in a diabetic environment via the MAPK pathway in VSMCs and that it possibly contributes to the acceleration of atherosclerosis. PMID- 26894026 TI - Laparoscopic biopsy-proven lupus nephritis in autosomal dominant polycystic kidney disease. AB - A 48-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with generalized edema and arthralgia. She showed evidences of acute glomerulonephritis including nephrotic-ranged proteinuria. Because her serologic test results were consistent with those for systemic lupus erythematosus (SLE), we performed laparoscopic renal biopsy that confirmed World Health Organization (WHO) class IV lupus nephritis. She was treated with steroids and intravenous cyclophosphamide pulse therapy and eventually started hemodialysis 8 years after the lupus nephritis was diagnosed. To our knowledge, this is the first case wherein a patient with ADPKD underwent a laparoscopic biopsy for diagnosing lupus nephritis. PMID- 26894025 TI - Hyperuricemia as a marker for progression of immunoglobulin A nephropathy. AB - BACKGROUND: The variable clinical and histopathological manifestations of immunoglobulin A nephropathy (IgAN) make it difficult to predict disease progression. A recent study showed that hyperuricemia, a condition common in hypertension and vascular disease, may contribute to renal dysfunction and histological changes including renal arteriosclerosis, tubular atrophy, and interstitial fibrosis. Herein, we investigated the clinical significance of uric acid level at the time of biopsy, as a marker of IgAN progression. METHODS: We included 193 patients with biopsy-proven IgAN. Renal disease progression was defined as serum creatinine elevation above 1.2 mg/dL or over 20% elevation from baseline. Hyperuricemia was defined as a serum uric acid level >=7.3 mg/dL in men and >=5.3 mg/dL in women, which were 1 standard deviation above the mean value in the normal subjects. RESULTS: The hyperuricemia group (n=50) had higher blood pressure, body mass index, and serum creatinine, and a greater amount of proteinuria and a lower glomerular filtration rate than the nonhyperuricemia group (n=143). Hyperuricemia increased the risk of IgAN progression (odds ratio, 4.53; 95% confidence interval, 1.31-15.66). The disease progression group (n=26) had a greater frequency of hyperuricemia, hypertension, and nephrotic range proteinuria than the nonprogression group (n=119). The renal survival analysis showed that the hyperuricemia group had a higher rate of IgAN disease progression. CONCLUSION: Hyperuricemia at the time of diagnosis is an important marker for IgAN progression. PMID- 26894027 TI - Cytokine gene polymorphisms: Can these differentiate renal disease entities? PMID- 26894028 TI - A case of membranous nephropathy associated with relapsing polychondritis. AB - Relapsing polychondritis (RP) is a rare, chronic, and potentially fatal multisystemic inflammatory disorder targeting cartilaginous structures. This disorder is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and hematologic disorders, but renal involvement is unusual. In the literature, associated renal pathology includes mesangial expansion, IgA nephropathy, tubulointerstitial nephritis, and segmental necrotizing crescentic glomerulonephritis. We report a case of a 49-year-old male found to have RP and nephrotic syndrome, with confirmed membranous nephropathy on kidney biopsy. He responded well to corticosteroids and cyclosporine. This is the first case of renal associated RP confirmed by renal biopsy in Korea. Membranous nephropathy associated with RP has never before been reported. PMID- 26894029 TI - The use of tacrolimus in the management of minimal change disease. PMID- 26894030 TI - Understanding and exploiting hepcidin as an indicator of anemia due to chronic kidney disease. AB - Hepcidin, produced by the liver, is the master regulator of iron balance. Serum hepcidin is increased by high iron stores, blocks intestinal iron absorption, and impairs storage iron release. Conversely, iron deficiency lowers hepcidin levels and enhances intestinal iron absorption and the release of storage iron. As with ferritin, hepcidin is an acute phase reactant. Consequently, inflammation increases hepcidin and leads to impaired iron absorption, lowers serum iron and transferrin saturation, and contributes to the anemia of chronic kidney disease (CKD). We review the physiology of iron absorption, its relationship to hepcidin and the transmembrane iron transporter ferroportin, the role of hepcidin in CKD related anemia, and the possible diagnostic implications and limitations of using hepcidin as a marker of iron status. PMID- 26894031 TI - Where do we stand on human diabetic nephropathy? PMID- 26894032 TI - Erratum: Asymptomatic renal pseudoaneurysm after percutaneous renal biopsy [Volume 32, Issue 2, June 2013, pp. 87-89]. AB - [This corrects the article DOI: 10.1016/j.krcp.2013.04.006.]. PMID- 26894034 TI - Clinicopathological role of kidney injury molecule-1 in immunoglobulin A nephropathy. AB - BACKGROUND: Urinary kidney injury molecule-1 (KIM-1) is an early and sensitive biomarker of acute kidney injury, but it is unclear if it is a biomarker of chronic glomerulonephritis. We evaluated whether urinary KIM-1 levels in patients with immunoglobulin A (IgA) nephropathy can be a marker to reflect clinicopathological severity and predict the prognosis. METHODS: We measured urinary KIM-1 levels in 40 patients (15 males; mean age 36.6+/-12.9 years) with IgA nephropathy and 10 healthy people (5 males; mean age 37.3+/-9.6 years) as controls. The correlation of urinary KIM-1 levels with patients' clinical parameters, histological grades, and follow-up data were analyzed using the modified H. S. Lee grading system and tubulointerstitial change scores. RESULTS: Urinary KIM-1 levels were higher in patients with IgA nephropathy than healthy controls (P=0.001). Univariate and multivariate regression analyses showed that urinary KIM-1 levels had a direct correlation with H. S. Lee grade and tubulointerstitial inflammation (P=0.004 and P=0.011, respectively). CONCLUSION: In patients with IgA nephropathy, urinary KIM-1 has a significant correlation with histopathologic severity. PMID- 26894033 TI - Comprehensive approach to diabetic nephropathy. AB - Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin-angiotensin aldosterone system inhibitors (RAASi). The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN. PMID- 26894036 TI - Assessing Risk-Taking in a Driving Simulator Study: Modeling Longitudinal Semi Continuous Driving Data Using a Two-Part Regression Model with Correlated Random Effects. AB - Signalized intersection management is a common measure of risky driving in simulator studies. In a recent randomized trial, investigators were interested in whether teenage males exposed to a risk-accepting passenger took more intersection risks in a driving simulator compared with those exposed to a risk averse peer passenger. Analyses in this trial are complicated by the longitudinal or repeated measures that are semi-continuous with clumping at zero. Specifically, the dependent variable in a randomized trial looking at the effect of risk-accepting versus risk-averse peer passengers on teenage simulator driving is comprised of two components. The discrete component measures whether the teen driver stops for a yellow light, and the continuous component measures the time the teen driver, who does not stop, spends in the intersection during a red light. To convey both components of this measure, we apply a two-part regression with correlated random effects model (CREM), consisting of a logistic regression to model whether the driver stops for a yellow light and a linear regression to model the time spent in the intersection during a red light. These two components are related through the correlation of their random effects. Using this novel analysis, we found that those exposed to a risk-averse passenger have a higher proportion of stopping at yellow lights and a longer mean time in the intersection during a red light when they did not stop at the light compared to those exposed to a risk-accepting passenger, consistent with the study hypotheses and previous analyses. Examining the statistical properties of the CREM approach through simulations, we found that in most situations, the CREM achieves greater power than competing approaches. We also examined whether the treatment effect changes across the length of the drive and provided a sample size recommendation for detecting such phenomenon in subsequent trials. Our findings suggest that CREM provides an efficient method for analyzing the complex longitudinal data encountered in driving simulation studies. PMID- 26894037 TI - Toxic effects of the administration of Mikania glomerata Sprengel during the gestational period of hypertensive rats. AB - Herbal medicine is an ancient practice that has been gaining acceptance of the medical class through scientific studies that prove its effectiveness. However, its use should still be cautious. Medicinal plants have potential toxic effects not yet discovered, and may have unproven interactions with other medications. The use of drugs during pregnancy is still very dangerous and vigorously studied; however, there are few studies of herbal medicines in pregnant women. Existing studies prioritize on teratogenic or abortifacient effects. The aim of this study was to analyze the toxic effects of Mikania glomerata Sprengel administration, popularly known as "guaco" during the gestational period of hypertensive rats. For this experimental groups consisting of pregnant Wistar rats received treatments with guaco extract (1 to 2 mL). In order to analyze the possible toxic effects of guaco during pregnancy, weight gain of rats was assessed during pregnancy; reproductive performance of rats, morphological parameters, and fetal placental histology were compared. Although some parameters presented significant differences, we can conclude that changes prioritized by literature, such as toxicity, vasodilation and hypotension, have not been caused by guaco. The only fetal changes observed were due to the maternal hypertension. Some studies have reported vasodilator and hypotensive effects of guaco. However, only a few studies exist, and its actual effects remain unknown. Specific studies should be developed with higher doses of guaco for a definitive conclusion of its toxic and non-toxic effects. PMID- 26894035 TI - Comparison of exit site infection and peritonitis incidences between povidone iodine and normal saline use for chronic exit site care in peritoneal dialysis patients. AB - BACKGROUND: Catheter-related exit site infection is a major risk factor for the development of peritonitis and can contribute to failure of treatment maintenance in peritoneal dialysis (PD) patients. Although povidone-iodine can be used for exit site care, the irritation induced by the local application of povidone iodine could lead to secondary infection. Therefore, we evaluated the clinical effectiveness of normal saline compared with povidone-iodine as a method of exit site care in chronic PD patients. METHODS: In all, 126 patients undergoing PD treatment for>6 months between January 2006 and December 2009 were enrolled. Data were retrospectively analyzed for the incidence of exit site infection and peritonitis for 2 years prior to and after December 2007. In addition, we identified the incidences of catheter-related infections during follow-ups from January 2010 to December 2013. RESULTS: The participants' mean age was 58.8+/ 12.9 years. The incidences of exit site infection and peritonitis were one episode per 64.6 patients-months and one episode per 40.4 patients-months in the povidone-iodine group, respectively, whereas these were one episode per 57.5 patients-months and one episode per 45.6 patients-months in the normal saline group, respectively. Whereas Gram-positive bacteria most frequently caused catheter-related infections in both groups, culture-negative infections were dominant in the normal saline group. CONCLUSION: Exit site care using normal saline did not increase the incidence of exit site infection and peritonitis. Therefore, normal saline may be an alternative treatment for exit site care in patients receiving PD. PMID- 26894038 TI - Cardiotoxicity of Senna occidentalis in sheep (Ovis aries). AB - The cardiotoxicity of Coffee senna (Senna occidentalis) was investigated in sheep that were fed diets containing its seeds, which are recognized as the most poisonous part of such weed. Dianthrone, the main toxic component of S. occidentalis, is known to impair mitochondrial oxidative phosphorylation, leading to myofiber degeneration. In this study, fifteen ewes were fed 0%, 2% or 4% of seeds of S. occidentalis for 63 days. Non-specific markers of myocyte injury and electrocardiograms were undertaken at baseline, and at 14, 35, and 63 days after the animals were first fed the diets, while histopathology of heart samples was performed at the very end of the study. Our results showed an increase in serum AST and LDH over time, while CK-MB did not change significantly. Changes that could be ascribed to myocardial damage were not documented in the electrocardiograms. Cardiac histopathology demonstrated only mild-to-moderate vacuolar degeneration, myofiber edema and disarray, structural disorganization, and cellular necrosis. In conclusion, S. occidentalis caused myocardial fiber degeneration in a dose-dependent fashion, but the electrocardiogram was not able to identify these lesions non-invasively. Because the markers of myofiber injury used in this study lack specificity, they may not be used to support cardiac impairment objectively, despite some of them did change over time. PMID- 26894039 TI - Operational contemporary diagnostic reasoning. PMID- 26894040 TI - Porcelain gallbladder. PMID- 26894041 TI - Conidial heads (Fruiting Bodies) as a hallmark for histopathological diagnosis of angioinvasive aspergillosis. AB - Aspergillosis is a mycosis that afflicts immunocompetent and immunocompromised hosts; among the former it exhibits different clinical pictures, and among the latter the infection renders an invasive form of the disease. The histologic diagnosis of invasive aspergillosis is somewhat challenging mostly because of some morphological similarities between other fungi. However, when present, the conidial heads are pathognomonic of aspergillosis. The authors present the case of a 68-year-old woman who was submitted to autologous hematopoietic stem cell transplantation in the pursuit of multiple myeloma treatment. The post transplantation period was troublesome with the development of severe neutropenia, human respiratory syncytial virus pneumonia, and disseminated aspergillosis, which was suspected because of a positive serum galactomannan antigen determination, and resulted in a fatal outcome. The autopsy findings showed diffuse alveolar damage associated with angioinvasive pulmonary aspergillosis with numerous hyphae and conidial heads in the lung parenchyma histology. The authors call attention to the aid of autopsy in confirming the diagnosis of this deep mycosis, since only the research of the galactomannan antigen may be insufficient and uncertain due to its specificity and of the possibility of false-positive results. PMID- 26894042 TI - Bacterial sinusitis and its frightening complications: subdural empyema and Lemierre syndrome. AB - The symptoms of a previously healthy 14-year-old female with an initial history of tooth pain and swelling of the left maxillary evolved to a progressive headache and altered neurological findings characterized by auditory hallucinations, sleep disturbances, and aggressiveness. She was brought to the emergency department after 21 days of the initial symptoms. An initial computed tomography (CT) scan showed frontal subdural empyema with bone erosion. The symptoms continued to evolve to brain herniation 24 hours after admission. A second CT scan showed a left internal jugular vein thrombosis. The outcome was unfavorable and the patient died on the second day after admission. The autopsy findings depicted rarefaction of the cranial bone at the left side of the frontal sinus, and overt meningitis. The severe infection was further complicated by thrombophlebitis of the left internal jugular vein up to the superior vena cava with septic embolization to the lungs, pneumonia, and sepsis. This case report highlights the degree of severity that a trivial infection can reach. The unusual presentation of the sinusitis may have wrongly guided the approach of this unfortunate case. PMID- 26894043 TI - Congenital generalized lymphangiectasia: a rare developmental disorder for non immune fetal hydrops. AB - Firstly described by Rudolf Virchow in the 19th century, congenital generalized lymphangiectasia is a rare entity characterized by dilation of lymphatic vessels, and was recently classified in primary or secondary lymphangiectasia. Generalized forms may be diagnosed during pre-natal follow-up with ultrasound examination, and, depending on its severity, the newborn outcome is very poor. The authors report the case of a female newborn with a previous diagnosis of fetal hydropsy who was born after a full-term gestation with respiratory failure due to bilateral voluminous pleural effusion and ascites. Physical examination also disclosed syndromic facies. Despite all efforts of the intensive supportive care, the patient died after 24 days of life. The autopsy findings were consistent with the diagnosis of congenital pulmonary lymphangiectasia. The authors call attention to this rare diagnosis in patients with cavitary effusion and respiratory insufficiency at birth. PMID- 26894044 TI - Streptococcus agalactiae septicemia in a patient with diabetes and hepatic cirrhosis. AB - Streptococcus agalactiae is a well-known pathogen during pregnancy and in neonates. Among non-pregnant adults, invasive infection, although rare, is showing increasing frequency, especially in chronically ill, immunosuppressed, or older patients. Although rare, the clinical features of meningeal infection caused by S. agalactiae are similar to other bacterial meningitis. The authors report the case of a middle-aged man previously diagnosed with hypertension, diabetes mellitus, and alcoholic liver cirrhosis, who was admitted at the emergency department with a Glasgow Coma Scale of 11/12, generalized spasticity, bilateral Babinski sign, and hypertension. The clinical outcome was bad, with refractory shock and death within 24 hours of hospitalization. The bacteriological work-up isolated S. agalactiae in the cerebral spinal fluid (CSF), blood, and urine. An autopsy revealed meningoencephalitis, acute myocardial infarction, and pyelonephritis due to septic emboli. The authors point out the atypical CSF findings, the rapid fatal outcome, and the importance of including this pathogen among the etiologic possibilities of invasive infections in this group of patients. PMID- 26894045 TI - The infantile-onset form of Pompe disease: an autopsy diagnosis. AB - Pompe disease (PD) is a rare, inherited autosomal recessive metabolic disorder caused by the deficiency of the lysosomal acid alpha-glucosidase (GAA) enzyme described in 1932 by the Dutch pathologist Joannes Cassianus Pompe. The prevalence of PD ranges from 1:40,000 to 1:300,000 births and depends on geographic and ethnic factors. Clinical manifestations may vary from a rapidly progressive disabling disease with cardiomegaly, hepatomegaly, weakness, generalized hypotonia, and death within the first year of life, to a mild presentation characterized by slowly progressive myopathy predominantly involving the skeletal muscles. The laboratory diagnostic gold standard is represented by the determination of the alpha-glucosidase activity. However, the muscle histology may also yield the diagnosis by evaluating the tissular glycogen accumulation. Until recently, supportive measures constituted the unique available therapy. Currently, the administration of the recombinant GAA is being used with promising results. The authors present the case of a 5-month-old boy, previously diagnosed with hypertrophic cardiomyopathy since the age of 2 months, who presented acute heart failure accompanied by biventricular dilation followed by refractory shock and death. The autopsy findings confirmed the glycogen accumulation disease. PMID- 26894046 TI - Cardiac sarcoidosis with severe involvement of the right ventricle: a case report. AB - We present the case of a patient who underwent cardiac transplantation with the diagnosis of idiopathic dilated cardiomyopathy. Once the explanted heart was examined, a type of granulomatous myocarditis compatible with cardiac sarcoidosis was observed. However, there was severe involvement of the right ventricle, with markedly reduced width of the muscular layer and extensive fibrofatty replacement, findings similar to the ones encountered in cases of arrhythmogenic right ventricular cardiomyopathy (ARVC). Confocal immunofluorescence analysis revealed a reduced signal for plakoglobin and desmoplakin at the cardiac intercalated disks. The immunoreactive signal for desmin showed the typical sarcomeric distribution but not a concentrated signal at the intercalated disks, a pattern previously seen in an 11-year-old girl with Carvajal syndrome bearing a C-terminal truncating mutation in the desmoplakin gene. This case illustrates the difficult and challenging work involved in performing a differential diagnosis among idiopathic dilated cardiomyopathy, isolated cardiac sarcoidosis, and ARVC, all of which are clinical entities known to masquerade as one another. PMID- 26894047 TI - Subserous lymphangioma of the sigmoid colon: an uncommon cause of acute abdomen in pediatric patients. AB - Lymphangioma is a rare, benign lesion derived from a malformation of the lymphatic system, which is more frequently found in the head, neck, and axilla. However, it may be present anywhere in the body, and the diagnosis involves adults as children with some distinct clinical features among them. In pediatric patients, abdominal cystic lymphangioma occurs mostly in the mesentery presenting abdominal pain, intestinal obstruction, or, more rarely, hemorrhage. The authors report the case of a child with a short-course history of fever, abdominal pain, and constipation. The physical examination disclosed the presence of an abdominal mass and signs of peritoneal irritation. Imaging was consistent with a cystic lesion compressing the sigmoid colon and laterally displacing the remaining loops. Exploratory laparotomy was undertaken, and a sigmoidectomy, followed by Hartman's colostomy, was performed. Histological examination revealed the nature of the lesion as a cystic lymphangioma. The authors highlight the clinical features of this entity and call attention to this disease in the differential diagnosis of acute abdomen or abdominal pain, mainly in pediatric patients. PMID- 26894048 TI - Ganglion cysts in the lateral portal region of the knee after arthroscopy: report of two cases. AB - A ganglion cyst (GC) is a mucinous or gelatinous-filled benign tumor overlying a joint or tendon sheath, which commonly arises in the dorsal and volar wrist side but may occur anywhere in the body. Although cystic lesions around the knee are common, the occurrence of GCs are rare. Ganglia may arise from intra or extra articular, soft tissue, intraosseous, or periosteal location. Symptoms may vary according to the size and location. After the more frequent performance of magnetic resonance imaging for the assessment of a knee joint, the number of incidental, asymptomatic lesions have been increasingly diagnosed. The etiology of GC remains unclear; however, trauma and a flaw in the joint tissues may explain its appearance. The authors report two cases of women aged 47 years and 37 years who presented pain and swelling in their left knees following arthroscopic partial medial meniscectomy. The former was surgically treated and had a favorable outcome, while the latter had conservative treatment and a gloomy outcome. PMID- 26894050 TI - Morphometric Study of Nasal Bone and Piriform Aperture in Human Dry Skull of Indian Origin. AB - INTRODUCTION: Nasal bone and piriform aperture shows racial and geographical differences because of variable climate. The aim of this study was to evaluate the dimensions (maximal width and length), the size and the shape of the piriform aperture (PA) and their sexual dimorphism in North Indian adult. MATERIALS AND METHODS: In this observational study, dimension of piriform aperture and nasal bone were measured using digital vernier caliper after assessing landmarks around the piriform aperture on the norma frontalis in Frankfurt plane in 40 skull of Indian orgin. RESULTS: The mean width of the piriform aperture was 24.9+/-1.59 mm in males and 22.77+/-1.57 mm in females, the mean length was 29.57+/-3.28mm in females and 31.16+/-3.58mm in males. The difference between males and females was significant, and our data correlates well with the previously data acquired from humans skulls. Most of North Indian skulls have platyrhine type of piriform aperture (triangular to oval shape with pyriform aperture index of 0.79). Mean length and width of nasal bone were 17.58+/-2.47mm and 12.1+/-0.97mm respectively without sexual. CONCLUSION: Shape and size analysis of the piriform aperture and nasal bone showed the existence of a significant sexual dimorphism. These results encourage us to go further with functional and imaging correlations. This study will also be helpful in forensic research and anthropology. PMID- 26894049 TI - Morphometric Study of Subpubic Angle in Human Fetuses. AB - INTRODUCTION: The symphysis pubis is formed at the confluence of the pubic bones. Each pubic bone consists of a body and two rami; the superior ramus is joined with the ilium and the inferior ramus with the ischium. The two bones meet in the midline at the pubic symphysis. The two inferior rami at the lower border of pubic symphysis subtend the subpubic angle. In females the subpubic angle is more than 90 degrees and in males it is less than 90 degrees . Most of the previous studies on the subpubic angle have been in children or adults, therefore data on fetuses did merit. AIM: The aims of the present study were to measure the subpubic angle in developing human fetuses of different gestational age, whether it is sex dependent and to compare the results with that in the adults. MATERIALS AND METHODS: A cross-sectional study conducted in the Department of Anatomy JN Medical College, AMU Aligarh, over a period of two years. A total of 41 fetuses immersion fixed in 10% formalin were obtained from the museum department of anatomy. For the purpose of study fetuses were divided into five groups according to gestational age. Group I comprises fetuses of 14-18weeks, group II 19-22weeks, group III 23-26weeks, group IV 27-30weeks, groupV >30weeks of gestation. Pubic symphyses were dissected, cleaned and subjected to radiological examination in the anteroposterior plane. With the help of radiographs subpubic angle was measured. Readings obtained were analysed statistically. RESULTS: Subpubic angle ranged between 58 degrees -64 degrees throughout intrauterine life. Maximum angle (63 degrees - 64 degrees ) was observed in group I and V and in the rest of the groups it was less than 60 degrees , with highly significant (p-value<0.001) increase in the last group. Statistically significant sexual dimorphism was observed in group I and II fetuses (p-value <0.001). Subpubic angle was more in females during the first half and in the terminal part of gestation. CONCLUSION: Subpubic angle remained acute throughout the intrauterine life, with significant widening in fetuses more than 30 weeks of gestation. Marked sexual dimorphism was noticed only in fetuses of 14-18 weeks and 19-22 weeks of gestation fetuses, although the values were invariably less than 90 degrees (acute) in both the sexes but in females towards the higher side as in adults. Assessment of symphysis and subpubic arch during antenatal ultrasonography of pregnant women can be done to diagnose congenital widening of the symphysis or absence of symphysis altogether. PMID- 26894051 TI - Is There a Correlation between Languages Spoken and Intricate Movements of Tongue? A Comparative Study of Various Movements of Tongue among the Three Ethnic Races of Malaysia. AB - INTRODUCTION: Tongue is mainly used for taste, chewing and in speech. In the present study, we focused on the secondary function of the tongue as to how it is used in phonetic pronunciation and linguistics and how these factors affect tongue movements. OBJECTIVE: To compare all possible movements of tongue among Malaysians belonging to three ethnic races and to find out if there is any link between languages spoken and ability to perform various tongue movements. MATERIALS AND METHODS: A total of 450 undergraduate medical students participated in the study. The students were chosen from three different races i.e. Malays, Chinese and Indians (Malaysian Indians). Data was collected from the students through a semi-structured interview following which each student was asked to demonstrate various tongue movements like protrusion, retraction, flattening, rolling, twisting, folding or any other special movements. The data obtained was first segregated and analysed according to gender, race and types and dialects of languages spoken. RESULTS: We found that most of the Malaysians were able to perform the basic movements of tongue like protrusion, flattening movements and very few were able to perform twisting and folding of the tongue. The ability to perform normal tongue movements and special movements like folding, twisting, rolling and others was higher among Indians when compared to Malay and Chinese. CONCLUSION: Languages spoken by Indians involve detailed tongue rolling and folding in pronouncing certain words and may be the reason as to why Indians are more versatile with tongue movements as compared to the other two races amongst Malaysians. It may be a possibility that languages spoken by a person serves as a variable that increases their ability to perform special tongue movements besides influenced by the genetic makeup of a person. PMID- 26894053 TI - A Rare Case of Mandibular Exostoses and its Review. AB - Mandibular exostosis is a type of bony prominence caused due to hyperostosis in the mandibular bone. They are benign, broad-based surface masses on the outer or facial aspect of the jaw bones; slowly enlarge over the years to form the bulky masses. During the period between the 10th to 13th week of intrauterine life, changes in the structure of the Meckel's cartilage and the protrusion of the medial lamina of the mandible onto the cartilage can result in the formation of such exostosis. We discuss here a very rare case of a 49-year-old male, in which the buccal exostoses formed underwent changes in size and shape due to certain factors, resulting in a bony bar formation in the mandibular anterior region. PMID- 26894052 TI - Two Cases of Rectus Sternalis Muscle. AB - The sternalis muscle, an uncommon anatomical variant of the chest wall musculature, though perhaps well known to anatomists, is quite unfamiliar to clinicians and radiologists despite attempts to highlight its clinical importance in recent years. During routine dissection for undergraduate medical teaching, in the department of anatomy, we came across two cases of sternalis muscle. The first was a unique case of unilateral right sternalis with contralateral insertion on the left sternocleidomastoid, and the second case where bilateral presence of the muscle was noted with ipsilateral insertion. The former was supplied by medial pectoral nerve and the latter by lower intercostal nerves. Usually present between the pectoral and superficial fasciae, wide ranging prevalence and morphology have been attributed to this muscular variant. Opinions differ on its development and nerve supply. Its presence can be misdiagnosed as a wide range of benign and malignant anterior chest wall lesions and tumours, but it is also of great use as a pedicle flap or flap microvascular anastomosis in reconstructive surgeries of anterior chest wall, head and neck and breast. In this paper, two cases of sternalis muscle which presented very differently from each other are discussed. PMID- 26894054 TI - Evaluation of Serum Pregnancy Associated Plasma Protein-A & Plasma D-Dimer in Acute Coronary Syndrome. AB - INTRODUCTION: Acute coronary syndrome (ACS), a spectrum comprising unstable angina pectoris, ST Elevated Myocardial Infarction (STEMI) & Non ST Elevated Myocardial Infarction (NSTEMI) is the major cause of presentation in Emergency Department today. Though ECG and cardiac enzymes are used for diagnosis, they mislead the diagnosis sometimes and delay in treatment initiation. This leads us to search certain new parameters which reflect the pathophysiology of ACS. Markers of plaque stability like Pregnancy Associated Plasma Protein-A and D Dimer, a marker of ongoing thrombosis are found to be better markers in early diagnosis. AIM: To evaluate the diagnostic competence of PAPP-A and D-Dimer in acute coronary syndrome over CK-MB and to compare with the inflammatory marker High Sensitive C-Reactive Protein (hs-CRP) which is associated with atherosclerosis. MATERIALS AND METHODS: Fifty patients presenting with acute onset of chest pain to Emergency Department with or without ECG changes served as cases and 50 healthy people served as controls. Serum PAPP-A is measured by Enzyme Linked Immunosorbent Assay (ELISA), D-Dimer and hs-CRP by using Latex Turbidimetry method. RESULTS: A statistical significant difference of PAPP-A and D-Dimer was noted between the ACS and controls (p < 0.001) whereas CK-MB shows no much difference (p 0.09). Statistically significant positive correlation is noted between parameters. CONCLUSION: PAPP-A marker of plaque instability and D-Dimer marker of ongoing thrombosis are raised in acute coronary syndrome and thus can be considered as one of the marker in ACS for diagnosis. PMID- 26894056 TI - Assessment of Various Biochemical Parameters and BMI in Patients with Skin Tags. AB - INTRODCTION: Acrochordon or fibroepithelial polyp, commonly known as Skin tags (STs) are one of the most common benign skin condition, consisting of skin projecting from the surrounding skin, usually occurring on the eyelids, neck and axillae. Studies have found an association of STs with conditions such as obesity, diabetes mellitus and atherogenic lipid profile. Abdominal obesity and the consequent insulin resistance are said be important contributing factors for diabetes, dyslipidaemia and cardiovascular disease. AIM: To highlight the association of lipid profile, BMI, glucose, HbA1c and leptin levels in patients with STs. MATERIALS AND METHODS: This was a case control study conducted at tertiary care hospital in South India from April 2013 to May 2014. The cases were chosen those who are having minimum of 3 STs attending the dermatology clinic. A total of 171 patients were screened, out of which 126 satisfied the criteria for inclusion and were included in the final analysis. The significance of the difference between the groups was assessed by Student t-test (two tailed, independent) to find the significance on continuous scale between two groups on metric parameters, between cases and controls and p-value of <0.05 were considered as statistically significant. RESULTS: Maximum cases were in males and in age group of 41-50 years. There was significant association between STs and triglycerides, low density lipoprotein, very low density lipoprotein cholesterol and leptin levels. Other parameters were also altered but no statistically significant difference was seen. CONCLUSION: STs are associated with change in markers of obesity and dyslipidaemia. Patients with STs need suitable interventions like weight reduction, smoking cessation, change in dietary habits. STs may also play a role in early diagnosis of metabolic syndrome. PMID- 26894055 TI - Adipokines and their Relation to Endothelial Dysfunction in Patients with Chronic Kidney Disease. AB - INTRODUCTION: Chronic Kidney Disease (CKD) patients are at high risk of cardiovascular diseases (CVDs). Reduced nitric oxide (NO) bioavailability is a key element in connecting kidney disease to endothelial dysfunction (ED) and cardiovascular (CV) complications. Further, inflammation is implicated in ED in CKD. Besides these, adipose tissue factors were thought to have a role in inflammation and ED in CKD. AIM: It is proposed to evaluate the concentration changes of adipokines, inflammatory and ED markers in CKD patients compared to healthy controls. Further, to assess the associations between adipokines, inflammation and ED in CKD patients. MATERIALS AND METHODS: A total of 120 CKD patients were included and classified into 3 groups based on Glomerular filtration rate (GFR). Group I (n=40) patients had a GFR between 60-119 ml/min/1.73m(2) (stage I, II), group II (n=40) had 15-59 ml/min/1.73m(2) (stage III, IV) and group III (n=40) had <15 ml/min/1.73m(2) (stage V). Forty healthy subjects served as controls. Adiponectin, Leptin, Interleukin-10 (IL-10), Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) were estimated by ELISA. High sensitivity C-reactive protein (hsCRP) was estimated by immunoturbidimetry and NO by Griess method. STATISTICAL ANALYSIS: Mann-Whitney U test was used to compare the difference in variables between controls and CKD patients. One-way ANOVA Kruskalwallis test was used for comparison of variables between groups in CKD patients. Spearman's rank correlation was used to explore the associations between variables. Simple univariate linear regression analysis was used to predict the value of variable from another variable. RESULTS: A significant increase in leptin, IL-6, TNF-alpha, IL-6/IL-10 ratio, hsCRP and decrease in adiponectin, IL-10, NO was observed in CKD patients compared to controls (p<0.05). In CKD patients, adiponectin, leptin, IL-6, IL-6/IL-10 ratio, TNF-alpha were significantly increased and IL-10 levels were decreased from group I to group III (p<0.05). In group III CKD patients IL-6 showed a significant negative correlation with NO (r=-0.557; p=0.005). In linear regression analysis also, IL-6 showed a significant negative association with NO (B+/-SE=-0.038+/ 0.11; p=0.002) in CKD patients. CONCLUSION: The present study demonstrates that adipokine levels are altered from initial to final stages of CKD due to renal dysfunction which in association with an exaggerated inflammation may contribute to the ED and CV events. PMID- 26894057 TI - Evaluation of Specificity and Sensitivity of Oral Fluid for Diagnosis of Hepatitis B. AB - INTRODUCTION: Hepatitis B viral infection is a global health issue. Various screening and confirmatory serological tests have evolved in the past few decades for detection of hepatitis B. However, oral fluid as an alternative to blood could provide substantial advantages. The study aimed to evaluate the diagnostic efficacy of oral fluid in detecting hepatitis B surface antigen using Enzyme Linked Immunosorbent Assay (ELISA). MATERIALS AND METHODS: Salivary and blood samples were collected from 40 seropositive and 40 seronegative patients of hepatitis B viral infection and were subjected to ELISA test for hepatitis B surface antigen. Mann-Whitney U test was used to test the statistical significance and Kappa (K) statistic was used to assess the degree of agreement between serum and oral fluid samples. The p-value <0.05 was considered as significant value. RESULT: A sensitivity and specificity of 100% of oral fluid assay was obtained for the diagnosis of hepatitis B infection. The degree of agreement between saliva and serum for detection of hepatitis B was found to be perfect (Kappa value =1). CONCLUSION: Oral fluid testing can be an interesting, alternative for hepatitis B infection for diagnosis and screening for epidemiological purposes. Further research necessitates for the implementation of saliva as a diagnostic tool. PMID- 26894058 TI - Normal Motor and Sensory Nerve Conduction Velocity of Radial Nerve in Young Adult Medical Students. AB - INTRODUCTION: Normal nerve conduction velocity of radial nerve is essential for differential diagnosis of various type of radial neuropathies, C7 radiculopathy and nerve lesion. AIM: To study normal motor and sensory nerve conduction velocity of radial nerve in young adult medical students. MATERIALS AND METHODS: Fifty medical students of either sex from first year, aged between 17- 20 year, were recruited for this nerve conduction study of radial nerve using surface electrode. Motor Nerve Conduction Velocity (MNCV) and Sensory Nerve Conduction Velocity (SNCV) of radial nerve of both hand were taken out and analysed for statistical significance and standard deviation. RESULTS: The mean Motor Latency (ML) in right and left hand were 8.11 msec and 8.01msec respectively, Amplitude (A) 9.08mv and 8.65mv respectively and MNCV was 66.81m/sec and 67.05m/sec respectively. The SNCV were 51.41 m/sec and 51.48m/sec in the right and left hand respectively. CONCLUSION: The normative value of motor and sensory NCV of radial nerve in male and female young medical students were established. The data were within the favourable range as compared with the existing data from other researchers for radial nerve. There were no difference statistically found in the radial nerve motor and sensory NCV of right and left hand of either sex. PMID- 26894059 TI - A Comparative Analysis of Dietary Habits on Sensory Motor Association and Heart Rate Variability during Menstrual Cycle. AB - INTRODUCTION: Dietary habits can make a big difference on both physical and mental aspects of the body. Menstrual disorder frequently affects the quality of life of adolescent and young adult women. Menstrual cycle irregularities may be associated with psychological stress, and endocrine disturbances. Monitoring of sensory-motor association and cardiovascular activity across the menstrual cycle has not been evaluated with dietary habits. AIM: The present study was carried out to bridge the relationship between dietary habits and endogenous sex hormone mediated sensory motor association and heart rate variability (HRV) among young females during different phases of menstrual cycle. MATERIALS AND METHODS: The present study was carried out on healthy volunteered 100 female medical students in the age group of 19-25 years with regular menstrual cycle. Group I (n=45) vegetarians, Group II (n=25) eggetarians and Group III (n= 30) non-vegetarians, where n denotes the number of individuals in each group. Sensory-motor association (reaction time) and cardiovascular activity (HRV) was evaluated. RESULTS: We observed among all the dietary habits (vegetarians, eggetarians and non-vegetarians) the reaction time and HRV was comparable in follicular and menstrual phase, however it was significantly altered in luteal phase when compared to follicular and menstrual phase. Moreover, among all the dietary habits, non-vegetarians showed more significant alteration of reaction time and HRV in luteal phase when compared to vegetarians and eggetarians, as well as there was positive correlation between visual and auditory reaction time and negative correlation between LF and HF in luteal phase, among all the dietary habits. CONCLUSION: We concluded sensorimotor association and regulation of autonomic tone is modified in luteal phase comparable to follicular phase and menstrual phase; however non-vegetarian had showed more significant alterations as compared to eggetarians and vegetarians. These suggest that sympathetic nervous activities are predominant in the luteal phase as compared to follicular phase, and this sympathetic dominance is more among non-vegetarians, which may be due to their higher BMI. The alterations in the balance of ovarian hormones might be responsible for these changes. Long-term intake of vegetarian diets may facilitate vagal regulation of the heart without increasing the sympathetic modulations of the cardiovascular system. PMID- 26894060 TI - Study of Electrophysiological Changes in Sensory Nerves Among Diabetic Smokers. AB - INTRODUCTION: Neuropathy is one of the most troublesome complication affecting individuals with diabetes. The resultant loss of function in peripheral nerves causes loss of protective sensations and impairs patient's ability to perceive incipient or even apparent ulcerations in the feet. AIM: This study was undertaken to test the hypothesis of alteration in electrophysiological parameters of nerve before actual manifestations of neuropathy in type 2 diabetic patients and to analyse the effect of smoking on Sensory Nerve Conduction Velocity (SNCV) of diabetic subjects. MATERIALS AND METHODS: One hundred and twenty diagnosed diabetics were taken as cases while 30 healthy non diabetics were taken as control. Case group was divided into diabetic non-smoker and diabetic smoker. Diabetic smoker were further subdivided into light smoker, moderate smoker and heavy smoker according to smoking index. After detailed history and physical examination SNCV of median and ulnar nerve in upper limb and sural nerve in lower limb was performed. RESULTS: On comparison of SNCV of median and ulnar nerve of upper limb and sural nerve of lower limb between control and diabetic non-smoker only sural nerve of diabetic non smoker showed significant bilateral decrease. There was significant bilateral decrease in SNCV of median and ulnar nerve of diabetic heavy smoker when compared to control and diabetic non smoker. Similarly, SNCV of sural nerve of diabetic heavy smoker was significantly decreased when compared with control, diabetic non-smoker, diabetic light and moderate smoker. A negative and statistically significant correlation was found between SNCV and smoking index. CONCLUSION: Present study indicates that nerves of lower limbs are more susceptible to diabetic assault as compared to upper limb suggesting that long nerves are commonly affected. Also, apart from duration and severity of diabetes, smoking itself is an independent factor for diabetic neuropathy. PMID- 26894061 TI - Measuring Respiratory Pressures with Mercury Manometer in Low Economic Health Care Settings- An Analytical Study. AB - INTRODUCTION: Health care economics restricts many health centers from using hi tech diagnostics equipment. Mercury manometers are used for calibration of pressure transducers. If standardized it would be a cost effective, simple alternative to transducers in low economic settings. AIM: To analyse the feasibility of mercury manometer usage in respiratory pressure measurement. MATERIALS AND METHODS: The experimental study was conducted with 30 healthy volunteers of age group 17-19 yrs. They were recruited by using simple random sampling method. The volunteers were made familiarized to lab environment, instrument and techniques of maximum inspiratory (Pimax) and expiratory pressures (Pemax). Then parameters were recorded using mercury manometer connected to different syringes as mouth piece (2.5 ml, 10 ml, and 20 ml) and with sphygmomanometer. Statistical analysis was done by using IBM SPSS statistics version 21. RESULTS: The Pimax was 111.07 +/- 6.53 with a 2.5 ml syringe as mouth piece. With 20 ml syringe it was 61.47 +/- 9.98. PEmax with 2.5 ml syringe was 70.33 +/- 8.19 with a confidence limit of 2.93 and with sphygmomanometer was 99.33 +/- 8.16 with a confidence limit of 2.92. There was a change in recorded pressure and the correlation analysis result showed a significant difference from both above and below 10 ml mouth piece range. CONCLUSION: Mercury manometers could be used for recording respiratory pressures in low economic facilities once standardized. Size of syringe to be used as mouth piece needs further more works although this study finds 10 ml syringe as suitable. PMID- 26894062 TI - Alternate Nostril Breathing at Different Rates and its Influence on Heart Rate Variability in Non Practitioners of Yoga. AB - INTRODUCTION: Heart rate variability is a measure of modulation in autonomic input to the heart and is one of the markers of autonomic functions. Though there are many studies on the long term influence of breathing on HRV (heart rate variability) there are only a few studies on the immediate effect of breathing especially alternate nostril breathing on HRV. This study focuses on the immediate effects of alternate nostril breathing and the influence of different breathing rates on HRV. MATERIALS AND METHODS: The study was done on 25 subjects in the age group of 17-35 years. ECG and respiration were recorded before intervention and immediately after the subjects were asked to perform alternate nostril breathing for five minutes. RESULTS: Low frequency (LF) which is a marker of sympathetic activity increased, high frequency (HF) which is a marker of parasympathetic activity decreased and their ratio LF/HF which is a marker of sympatho/vagal balance increased immediately after 6 and 12 minutes in comparison to baseline values whereas there was no significant difference in the means of these components when both 6 and 12 minutes were compared. CONCLUSION: Immediate effects of alternate nostril breathing on HRV in non practitioners of yogic breathing are very different from the long term influence of yogic breathing on HRV which show a predominant parasympathetic influence on the heart. PMID- 26894063 TI - Can Panton Valentine Leukocidin Gene And Clindamycin Susceptibility Serve As Predictors of Community Origin of MRSA From Skin and Soft Tissue Infections? AB - INTRODUCTION: Community associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have begun to replace Hospital Associated MRSA (HA-MRSA) strains in hospital settings all over the world. With the epidemiological distinctions between these strains beginning to become ill-defined, the categorisation of a strain as CA-MRSA or HA-MRSA is dependent on molecular methods to detect the presence of SCCmec (Staphylococcal Cassette Chromosome mec) elements. However other markers like the presence of Panton Valentine Leukocidin toxin (pvl) genes or Clindamycin susceptibility may also be associated with community origin of MRSA. AIM: To determine the prevalence of CA-MRSA among MRSA strains isolated from skin and soft tissue infections and to evaluate the usefulness of Panton Valentine Leukocidin and Clindamycin susceptibility as markers of community origin of MRSA. MATERIALS AND METHODS: One hundred isolates of MRSA from skin and soft tissue were studied for the presence of SCCmec IV and V genes and Panton valentine leukocidin gene by Polymerase chain reaction. Inducible clindamycin resistance was screened for using the D-test. STATISTICAL ANALYSIS USED: Fischer's exact test. A p-value <0.05 was considered significant. RESULTS: Eighteen out of 100 MRSA strains were found to be CA-MRSA based on presence of SCCmecV. The proportion of Panton Valentine Leukocidin gene carriage among CA- MRSA as compared to HA-MRSA was found to be statistically significant (p<0.0001). Among the CA-MRSA strains, 94.4% were found to be susceptible to Clindamycin as against only 13.4% of the HA-MRSA strains (p<0.0001). The odds of an MRSA strain being CA-MRSA if it was both Clindamycin susceptible and PVL gene positive was calculated to be 68.25 (p<0.0001). CONCLUSION: Both Clindamycin susceptibility and pvl gene carriage were found to be independent predictors of community origin of MRSA, but taken together the association was highly significant. PMID- 26894064 TI - Enhancing Phenotypic Detection of ESBL in AmpC co-producers by using Cefepime and Tazobactam. AB - INTRODUCTION: Routine phenotypic methods employing clavulanate and third generation cephalosporins to detect ESBL are not promising for isolates that co produce an inhibitor-resistant beta lactamase like AmpC. AIM: Enhancing phenotypic detection of ESBL in AmpC co-producers by using cefepime and tazobactam. MATERIALS AND METHODS: A total of 245 isolates of Escherichia coli (123), Klebsiella spp. (87), Proteus spp.(20), Enterobacter spp. (9) and Citrobacter spp.(6) obtained over a period of 2 years from January 2013 to December 2014 from urine samples of hospitalized patients were studied. The isolates were simultaneously screened for ESBL and AmpC production. AmpC production was confirmed by modified three -dimensional test (MTDT). ESBL production was confirmed by original double disc synergy test, phenotypic disc confirmatory test (PDCT) and modified double disc synergy test (MDDST) and the results compared. RESULTS: AmpC production was confirmed in 113 (46.1%) isolates by modified three dimensional test out of 143 screened positive for AmpC. Of the 192 isolates screened positive for ESBL, ESBL production was confirmed in 162 (66.1%). DDST detected ESBLs in only134 (54.7%) while additional 28 (11.4%) ESBL positive isolates were detected by MDDST. PDCT detected total 145(59.2%) ESBL positive isolates, with cefotaxime and cefotaxime + clavulanate detecting 139 (56.7%) and ceftazidime and ceftazidime + clavulanate detecting additional 6 isolates. All the 28 (11.4%) isolates which were additionally detected ESBL producers by MDDST showed positive three dimensional test i.e. AmpC co producers. DDST detected ESBL in none of AmpC positive isolates while PDCT detected ESBL in 11 isolates showing AmpC co-production. In MDDST cefepime was the best cephalosporin in detecting ESBL in presence of AmpC production. It showed synergism with amoxicillin-clavulanate in 11(39.3%) isolates and in 24(85.7%) isolates with piperacillin-tazobactam. Third generation cephalosporins cefotaxime, ceftazidime and cefpodoxime were not able to detect ESBL in AmpC-co producers. CONCLUSION: Modification of double disc synergy tests that combine piperacillin-tazobactum with cefepime enhances the possibility of ESBL detection. PMID- 26894065 TI - Prevalence of LRTI in Patients Presenting with Productive Cough and Their Antibiotic Resistance Pattern. AB - AIM: To find out the prevalence of Lower Respiratory Tract Infection (LRTI) such as bacterial, fungal, mycobacterial infections etc. in patients with productive cough of duration less than 15 days and to rule out the patients having previous history of tuberculosis or having treatment of tuberculosis. MATERIALS AND METHODS: Outdoor and Indoor patients of Department of Medicine and Chest & TB, SRG hospital and Jhalawar Medical College, Jhalawar were included. After sample collection the specimens were sent to the Microbiology department, for processing of Gram staining, Acid fast staining, KOH mount and bacteriological culture and sensitivity. RESULTS: A total of 200 samples were obtained from the outpatient and inpatient Department of Medicine and Chest & TB of which 66% were male and 34% were female. Seventy seven percent of samples were culture positive for both single pathogen and mixed infection of which 56.5% were male and 20.5% were female as males are more at risk for LRTI. Klebsiella pneumoniae was the most prevalent pathogen (71/193), followed by coagulase positive Staphylococci i.e. COPS (43/193). More resistant pattern was found in coagulase negative Staohylococci (CONS) showed 61.11% Methicillin Resistant Staohylococci (MRS) incidence compared to 41.86% in COPS, also regarding Extended Spectrum Beta Lactamase (ESBL) production Escherichia coli showed incidence of 36.36% as compared to other gram negative bacilli. Pseudomonas aeruginosa was the most resistant organism found based on the antibiotic susceptibility pattern while Proteus mirabilis was the most sensitive organism. CONCLUSION: Lower respiratory tract infections can spread easily among community and indiscriminate use of antibiotics contributes to their therapeutic failure. Area-wise studies on antimicrobial susceptibility profiles are essential to guide policy on the appropriate use of antibiotics to reduce the morbidity and mortality and also to control the emergence of antimicrobial resistance in local area. PMID- 26894066 TI - Prevalence of Escherichia coli O157:H7 in Children with Bloody Diarrhea Referring to Abuzar Teaching Hospital, Ahvaz, Iran. AB - INTRODUCTION: Escherichia coli O157: H7 are recognized as important aetiological agents of diarrhea in children, particularly in developed countries. AIM: The aim of the study was to determine the rates of detection of E. coli O157: H7strains among children in Ahvaz, Iran. MATERIALS AND METHODS: From June 2010 to December 2010, 137 diarrheal stool samples of children were collected. E.coli was identified by standard microbiological techniques. O157 or O157:H7 subtypes discerned by serological tests. RESULTS: Of the 137 E. coli isolates, enteropathogens were found in 53 (38.7%) of the patients as follow: Shigella spp. (75.5%), EPEC (enteropathogenic E. coli) (16.9%), Campylobacter spp. (3.8%) and Salmonella spp. (3.8%). None of the isolated E. coli was O157:H7 serotype. CONCLUSION: This shows that non-O157:H7 E. coli are the major cause of paediatric infections in this region of Iran. PMID- 26894067 TI - Pleural Nocardiosis in an Immunocompetent Patient: A Case Report. AB - Nocardiosis is a rare infection that has attracted attention with its increased rate of occurrence in the recent years. In India there is a rare documentation of the pleural involvement in nocardiosis. We report here a case of pleural nocardiosis caused by Nocardia brasiliensis in an immunocompetent patient. This case highlights the importance of considering nocardiosis as a differential diagnosis in patients with pleural lesions. PMID- 26894068 TI - The Application of Pulsed Field Gel Electrophoresis in Clinical Studies. AB - Pulsed-field gel electrophoresis is a method applied in separating large segments of deoxyribonucleotide using an alternating and cross field. In a uniform magnetic field, components larger than 50kb pass a route through the gel and since the movement of DNA (Deoxyribonucleic acid) molecules are in a Zigzag form, separation of DNAs as bands carried out better via gel. PFGE in microbiology is a standard method which is used for typing of bacteria. It is also a very useful tool in epidemiological studies and gene mapping in microbes and mammalian cell, also motivated development of large-insert cloning system such as bacterial and yeast artifical chromosomes. In this method, close and similar species in terms of genetic patterns show alike profiles regarding DNA separation, and those ones which don't have similarity or are less similar, reveal different separation profiles. So this feature can be used to determine the common species as the prevalence agent of a disease. PFGE can be utilized for monitoring and evaluating different micro-organisms in clinical samples and existing ones in soil and water. This method can also be a reliable and standard method in vaccine preparation. In recent decades, PFGE is highly regarded as a powerful tool in control, prevention and monitoring diseases in different populations. PMID- 26894069 TI - Volume Conductivity and Scatter Parameters as an Indicator of Acute Bacterial Infections by the Automated Haematology Analyser. AB - INTRODUCTION: Complete blood picture is the first and foremost investigation ordered for evaluation of acute infectious processes which require early and prompt intervention. With the advent of automated Coulter ((r)) Haematology analysers, the Volume, Conductivity & Scatter parameters of the leucocytes could be analysed for the early detection of the infections. AIM: To evaluate the clinical usefulness of Volume, Conductivity & Scatter parameters of neutrophils & monocytes in predicting the onset of acute bacterial infections. MATERIALS AND METHODS: Peripheral blood samples from 94 patients with infections (systemic infections n=36 & localised infections n=58) and 46 control subjects were studied using the Volume, Conductivity & Scatter parameters by the Coulter Haematology analyser. RESULTS: We observed a significant increase in the mean channel of neutrophil volume & mean channel of monocyte volume from patients with infections (both systemic & localised) as compared with control subjects (Mean Neutrophil Volume: 158.3 +/- 13.7 vs 137.2 +/- 4.3; p<0.001) & (Mean Monocyte Volume: 177.8+/- 16 vs 161.7 +/- 6.04; p <0.001). However, there was no significant difference in the Mean Neutrophil Volume of patients with systemic infection & localised infections (160.5+/-17.5 vs 156.8+/-10.5, p>0.05). CONCLUSION: The Volume, Conductivity & Scatter parameters like Mean Neutrophil Volume & Mean Monocyte Volume are more sensitive parameters and could prove to be a quick diagnostic indicator of acute bacterial infections. PMID- 26894070 TI - Elevated Factor VIII Levels and Shortened APTT in Recurrent Abortions. AB - INTRODUCTION: Thrombotic disorders have been found to be associated with recurrent abortions. Several risk factors have been identified. APTT reflects the common pathway and intrinsic pathway of coagulation cascade and hence is a good marker for thrombotic work. Elevated factor VIII: C has also been identified as risk factor for recurrent miscarriage. This study aims at identifying association of elevated factor VIII levels, shortened APTT and recurrent abortions in Indian population as little has been studied about this and the literature available is also based on studies done in European population. This study also aims to find whether shortened APTT can be an independent risk as well. MATERIALS AND METHODS: Women referred to the obstetrics department with a history of early recurrent early pregnancy loss (at least three pregnancy losses before 13 weeks of gestation) were included in this study. Exclusion criteria were elevated CRP levels, positive antiphospholipid antibodies, endocrine, immunological or anatomical cause of embryo demise. A total of 68 cases of recurrent abortion were included in this study, 68 normal pregnant females (<15 weeks of gestation) were also included as controls with no history of abortion. The age group of the cases as well as control was 20-45 years. Activated partial thromboplastin time and factor VIII assay (one stage APTT based) were done on the blood samples. RESULTS: Increased factor VIII levels were seen in 25 cases (36.4%); 19 cases showed shortened APTT (27.3%); 12 cases showed both increased factor VIII levels as well as shortened APTT (18%). All risk factors were negative in 36 cases (52.9%). None of the controls showed elevated factor VIII levels or shortened APTT. The mean APTT values of the control subjects was 31.01 and cases were 27.01 (p=0.001). The mean factor VIII levels of case were 152.85% and control 144.953% (p=0.012). CONCLUSION: There was significant association between recurrent abortions and elevated factor VIII :c levels and shortened APTT. Shortened APTT was also identified as an independent risk factor. PMID- 26894071 TI - Quality Measures in Pre-Analytical Phase of Tissue Processing: Understanding Its Value in Histopathology. AB - INTRODUCTION: Quality monitoring in histopathology unit is categorized into three phases, pre-analytical, analytical and post-analytical, to cover various steps in the entire test cycle. Review of literature on quality evaluation studies pertaining to histopathology revealed that earlier reports were mainly focused on analytical aspects with limited studies on assessment of pre-analytical phase. Pre-analytical phase encompasses several processing steps and handling of specimen/sample by multiple individuals, thus allowing enough scope for errors. Due to its critical nature and limited studies in the past to assess quality in pre-analytical phase, it deserves more attention. AIM: This study was undertaken to analyse and assess the quality parameters in pre-analytical phase in a histopathology laboratory. MATERIALS AND METHODS: This was a retrospective study done on pre-analytical parameters in histopathology laboratory of a tertiary care centre on 18,626 tissue specimens received in 34 months. Registers and records were checked for efficiency and errors for pre-analytical quality variables: specimen identification, specimen in appropriate fixatives, lost specimens, daily internal quality control performance on staining, performance in inter-laboratory quality assessment program {External quality assurance program (EQAS)} and evaluation of internal non-conformities (NC) for other errors. RESULTS: The study revealed incorrect specimen labelling in 0.04%, 0.01% and 0.01% in 2007, 2008 and 2009 respectively. About 0.04%, 0.07% and 0.18% specimens were not sent in fixatives in 2007, 2008 and 2009 respectively. There was no incidence of specimen lost. A total of 113 non-conformities were identified out of which 92.9% belonged to the pre-analytical phase. The predominant NC (any deviation from normal standard which may generate an error and result in compromising with quality standards) identified was wrong labelling of slides. Performance in EQAS for pre analytical phase was satisfactory in 6 of 9 cycles. CONCLUSION: A low incidence of errors in pre-analytical phase implies that a satisfactory level of quality standards was being practiced with still scope for improvement. PMID- 26894072 TI - An Affordable, Indigenous Polarizer-Analyser System with Inbuilt Retardation Plate Function to Detect Birefringence using 3D Glasses: An Experience. AB - INTRODUCTION: Polarizing microscope plays a vital role in few but unique situations. A pair of cross polarizers is used to confirm the presence of birefringent substances. Also, a red retardation plate is needed to evaluate the sign of birefringence. However, a polarizing microscope especially with retardation plate is very expensive. Thus, an affordable yet effective substitute using the 3D Polaroid glasses used for '3D movies' would enable widespread use of the polarizing system. AIM: To study the use of 3D polaroid glasses procured from cinema halls in detecting birefringence substances and to study the red retardation plate function in them. MATERIALS AND METHODS: Passive 3D Polaroid glasses were procured from cinema halls. They were arranged in aspecific manner to obtain polarized light. Red retardation plate function can be obtained by changing the arrangement of the glasses. These glasses were used with various available models of different light microscope manufacturers. Various specimens observed included amyloid deposits, woven and lamellar bone, skeletal muscle striations, urate crystals, cholesterol crystals, suture material and glove powder. The comparison was based on subjective interpretation of intensity and quality of birefringence. Sign of birefringence was also determined whenever relevant. RESULTS: The birefringence observed by our system was comparable to the commercially available polarizing system with respect to intensity and quality. Also, there were no false positive /negative results when compared with the commercial Polarizing microscope. Moreover, the system had an inbuilt red retardation plate to determine sign of birefringence. CONCLUSION: The system is efficient, cheap, easily accessible, portable and compatible with all models of light microscopes. PMID- 26894073 TI - Histopathological and Immunohistochemical Evaluation of Meningiomas with Reference to Proliferative Markers p53 and Ki-67. AB - INTRODUCTION: Meningiomas are slow growing primary central nervous system (CNS) tumours attached to the duramater, which arise from the meningothelial cells of the arachnoid. Grading of meningioma based on histological findings assisted with supplementary immunohistochemical studies, predicts the prognosis of meningioma with good precision. AIM: To evaluate proliferative markers and correlate with various histological subtypes and grade. MATERIALS AND METHODS: A total of 224 meningiomas, diagnosed between January1995 and October 2011were graded according to WHO 2007 criteria. Immunostaining for p53 and Ki-67 markers were performed on 100 cases. RESULTS: There was female predominance. There were 194 Grade I, 24 Grade II and 6 Grade III meningiomas. Brain invasion noted in 18(8%) meningiomas predominantly in grade III followed by grade II. Recurrence was seen in 7 (3.1%) cases, most common in psammomatous followed by angiomatous meningioma. Immunostaining showed p53 positivity in 72.5% of grade I, 83.3% of grade II and all the cases of grade III tumours. Ki-67 Labelling Index (LI) consistently increased from grade I to grade III tumours. CONCLUSION: p53 and Ki-67 LI correlated well with increasing histological grade and biological behaviour of meningioma. PMID- 26894074 TI - Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis. AB - Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID- 26894075 TI - Extraskeletal Osteosarcoma- A Case Report. AB - Osteosarcoma is the most common primary malignant bone tumour with a bimodal peak. But its extraskeletal variant is very rare. It arises exclusively in soft tissue without at any skeletal attachment. It accounts for 2% of all soft tissue sarcomas. It is usually diagnosed as an incidental finding during imaging. Here, we are presenting a case of extraskeletal osteosarcoma diagnosed incidentally during imaging in a 30 years old male for its rarity. PMID- 26894076 TI - Primary Epithelioid Angiosarcoma of Spleen: A Case Report and Review of Literature. AB - Splenic angiosarcomas are usually secondary tumours, and only few primary cases have been encountered. We report a unique primary case of epithelioid angiosarcoma arising in the spleen in a male patient 55-year-old and presented to our hospital as a medical emergency with acute abdomen and haemorrhagic ascitis. CT revealed splenic focal lesion and suggested that this abdominal haemorrhage was due to ruptured splenic haemangioma, thus abdominal exploration and splenectomy were done. The histopathological examination showed an infiltrating ill-defined growth formed of high grade epithelioid cells arranged in sheet-like growth pattern, with occasional papillary appearance. The presence of rudimentary vascular channels lined by epithelioid endothelial cells with occasional intraluminal erythrocytes suggested vascular tumour origin. The neoplastic cells showed diffuse expression of CD31 together with focal expression of cytokeratin (CK) and CD34. Because of its epithelioid morphology and unmistakable positivity for CK, this case may be easily misdiagnosed as a metastatic carcinoma, which is not uncommon finding in the spleen. Epithelioid angiosarcoma is a rare type of vascular tumour in the spleen, which co-expresses vascular and epithelial markers making its distinction from metastatic carcinoma is sometimes difficult. PMID- 26894077 TI - Giant left Atrial Myxoma Induces Mitral Valve Obstruction and Pulmonary Hypertension. AB - Atrial myxomas are the commonest benign primary tumours of the heart. They are generally 2 to 6 cm in size. Depending on their size and site may result in mitral valve obstruction which may lead to pulmonary hypertension. Clinical symptoms may suggest the presence of a myxoma but echocardiography is the mainstay of diagnosis and confirmation is by histopathology. A well-formed, organized thrombus is a common differential. The report of an unusually large left atrial myxoma that occurred in a 54-year-old male causing mitral valve obstruction and pulmonary hypertension is presented here. PMID- 26894078 TI - Molar Pregnancy Presents as Tubal Ectopic Pregnancy: A Rare Case Report. AB - The incidence of hydatidiform mole is 1 per 1000 pregnancies. The occurrence of hydatidiform mole in ruptured tubal pregnancy is very rare. We report an unusual case of molar pregnancy in the right fallopian tube which presented as an adherent adnexal mass. The present case conveys the importance of histological examination of products of conception which helps the pathologist to provide an appropriate diagnosis, thereby the clinician can offer appropriate counseling and follow up to the patient. PMID- 26894079 TI - Cytodiagnosis of a Cutaneous Clear Cell Malignancy: Metastatic Renal Cell Carcinoma on Chin. AB - Clear cell type of renal cell carcinoma (RCC) is most common urological malignancy. Several diagnostic challenges arise when it presents as a cutaneous nodule, being an uncommon presentation. Fine needle aspiration cytology (FNAC) of a cutaneous nodule is crucial for distinguishing primary tumours from metastatic tumours because cutaneous metastases represent a terminal stage of illness. Due to considerable overlap of cytomorphological features determination of primary warrants need of detailed clinical history and close inspection of every cytological detail. We report here a case of cutaneous metastasis of RCC on chin in a patient 11 years after nephrectomy. Though there are reports of RCC metastases diagnosed on histology, there are fewer cytology case reports. Cytological differential diagnosis has been discussed for arriving at the final diagnosis in case of clear cell tumours. Early and accurate diagnosis is mandatory for optimal treatment. Cytodiagnosis of cutaneous metastasis of RCC is uncommon due to its low suspicion index in cutaneous nodules. More so, it presents late and an unusual sites due to its resemblance to common dermatological diseases. PMID- 26894080 TI - Eccrine Porocarcinoma of the Scalp: A Rare Case Report with Review of Literature. AB - Eccrine porocarcinoma (EPC) is a potentially lethal neoplasm of the skin that arises from the intraepidermal portion of the eccrine sweat glands. It was previously known as eccrine adenocarcinoma or malignant eccrine poroma. It commonly occurs between 60 to 80 years of age, usually arising from hands and feet. However, few case reports on involvement of rare sites such as scalp, face and eyelids are present in literature. We herein report an unusual case of porocarcinoma arising on the right parieto occipital region of scalp in a 29-year old young female patient. To the best of our knowledge, there have been fewer than 20 cases of porocarcinoma arising on scalp with fewer than 10 cases seen in younger age group reported previously in the literature. PMID- 26894081 TI - Inflammatory Fibroid Polyp of the Ileum Presenting with Acute Intestinal Obstruction In An Adult Patient: A Case Report. PMID- 26894082 TI - Antecedent Drug Exposure Aetiology and Management Protocols in Steven-Johnson Syndrome and Toxic Epidermal Necrolysis, A Hospital Based Prospective Study. AB - AIM: The study sought to identify the magnitude and characteristic of severe cutaneous adverse reactions (SCAR's) like Steven-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). MATERIALS AND METHODS: A prospective study was conducted by the Department of Pharmacology in association with Department of Dermatology in SMHS hospital. The study was carried out from June 2013-June 2015 on hospitalized cases of cutaneous adverse drug reaction reporting in hospital. The SCAR's were reported in a structured questionnaire based on adverse drug reaction (ADR) reporting form provided by the Central Drug Standard Control Organization (CDSCO) Ministry of Health and Family welfare, Government of India. The SCAR's were analysed for their characteristics, causality, severity and prognosis. Causality assessment was done by using a validated ADR probability scale of Naranjo as well as WHO Uppsala Monitoring Center (WHO-UMC) system for standardized case causality assessment. The management protocol were analysed for their clinical outcome through a proper follow up period. RESULTS: A total of 52 hospitalized cases of cutaneous adverse drug reactions were reported during the study period. We identified a total of 15 cases (28%) of SCAR's involving 9(17%) of SJS and 6 (12%) of TEN. SJS was seen in 2(22%) males and 7(78%) females. TEN was seen in all females (100%) and in no male. Drugs implicated in causing these life threatening reactions were identified as anticonvulsant agents like carbamazepine (CBZ), phenytoin (PHT) and Lamotrigine (LTG), oxicam NSAID, Sulfasalazine and levofloxacin. Despite higher reported mortality rates in SJS and TEN all patients survived with 2 patients surviving TEN suffered from long term opthalmological sequelae of the disease. CONCLUSION: Present study suggest that drug induced cutaneous eruptions are common ranging from common nuisance rashes to rare life threatening diseases like SJS and TEN, SJS/TEN typically occur 1-3 weeks after initiation of therapy. Aromatic AED's, LTG, oxicam NSAID's, sulfasalazine and levofloxacin have a tremendous potential to trigger SCARS's. To ensure safe use of pharmaceutical agents and better treatment outcomes post marketing voluntary reporting of severe rare and unusual reactions remains inevitable. PMID- 26894084 TI - Risk of Acute Kidney Injury with Amikacin versus Gentamycin both in Combination with Metronidazole for Surgical Prophylaxis. AB - INTRODUCTION: Surgical site infection is one of the most important complication of surgery. It increases the mortality and morbidity. In order to decrease the incidence of surgical site infections perioperative antimicrobial prophylaxis has been recommended in certain types of clean and clean contaminated surgeries. Aminoglycosides are indicated as surgical prophylaxis for prevention of surgical site infection in patients with B-lactam allergy. AIM: The present study was carried out to study and compare the renal safety profile of single high dose gentamycin and amikacin as surgical prophylactic antibiotic. MATERIALS AND METHODS: Prospective and randomized study was carried out on 100 patients for over one year period in a tertiary care teaching hospital of western Uttar Pradesh, India. Patients in amikacin group received amikacin 15 mg/kg + metronidazole 500 mg intravenously single dose and those in the gentamycin group had gentamycin 5 mg/kg + metronidazole 500 mg intravenously single dose, one hour prior to incision. RESULT: A total of 16% patients of amikacin group and 24% patients of gentamycin group developed acute kidney injury within one week of drug administration. The rise in serum creatinine was temporary as all patients had normal serum creatinine level at one month follow up. CONCLUSION: Aminoglycoside intravenous single high dose is not safe as surgical prophylaxis. PMID- 26894083 TI - Effectiveness of Revised Pharmacology Record Books as a Teaching-Learning Method for Second Year Medical Students. AB - INTRODUCTION: The goal of teaching medical undergraduates Pharmacology is to form a sound foundation of therapeutics. The pharmacology record books are maintained as a part of the curriculum. The purpose of this study was to obtain feedback of the medical students about the new record adopted in the institution after major revision. MATERIALS AND METHODS: This was a questionnaire based study done in a Government Medical College of Kerala in February 2013. The data was analysed using SPSS. The feedback on clinical pharmacology exercises was given positive and negative scores. RESULTS: Majority (64.5%) opined that the content in pharmacology record was good. A total of 78.1% completed the record during discussions in practical classes. Majority wrote the records for understanding pharmacology. For 79.8% General Pharmacology exercises were most relevant, 33.8% considered Clinical Pharmacology exercises to be the most thought provoking. Drug use in special groups received the maximum positive score. CONCLUSION: The new improved pharmacology record is an effective teaching-learning method. Inclusion of more clinically oriented exercises has increased the interest of the students in the subject. PMID- 26894085 TI - A Randomised Open Label Comparative Clinical Trial on the Efficacy of Latanoprost and Timolol in Primary Open Angle Glaucoma. AB - INTRODUCTION: Timolol, a beta blocker, is the most commonly prescribed first line therapy in the treatment of primary open angle glaucoma. Latanoprost, a prostaglandin analogue, is a novel drug in glaucoma therapy. Its efficacy has to be proved for it to be included under the first line therapy in the treatment of primary open angle glaucoma. AIM: To compare the efficacy of Latanoprost with that of Timolol in the treatment of primary open angle glaucoma (POAG). MATERIALS AND METHODS: In this study the enrolled patients were randomly divided into two groups by block randomization. The sample size was determined to be 60 in each group. One group received 0.005% of Latanoprost once daily in the evening and the other group 0.5% of Timolol twice daily. The efficacy was measured in terms of intraocular pressure at scheduled follow up visits. RESULTS: At the start of the study, intraocular pressures of both groups were comparable. At the end point, reduction of intraocular pressure among Latanoprost group was significantly greater than that of Timolol group (9.72 vs 7.27, p = 0.002). CONCLUSION: Latanoprost was found to be superior to Timolol in reducing the intraocular pressure in treatment of patients with primary open angle glaucoma. PMID- 26894086 TI - Various Possible Toxicants Involved in Thyroid Dysfunction: A Review. AB - About 300 million people across the world suffer from thyroid gland dysfunction. Environmental factors play an important role in causation of autoimmune thyroid diseases in susceptible individuals. Genetics contributes to 70% of the risk. In order to reduce the risk, we need to understand the association of environmental agents with thyroid dysfunction. These factors are especially relevant for those at increased risk due to positive family history. The ideal study to see the impact of a thyroid toxicant consists of directly measuring the degree of exposure to toxicant in an individual with his thyroid status. Knowledge of various factors influencing thyroid dysfunction can help in interpreting the results of such studies in a better way. This article is an attempt to highlight the various possible toxicants affecting thyroid function so that adequate measures can be undertaken to control excessive exposure in future to reduce the prevalence of thyroid disorders. PMID- 26894087 TI - A Comparison Between Phorbol 12 Myristate 13 Acetate and Phorbol 12, 13 Dibutyrate in Human Melanocyte Culture. AB - INTRODUCTION: Melanocyte culture is an integral part of the studies of skin biology and cosmetic applications. After the introduction of selective medium for the culture of human melanocyte using Phorbol 12-myristate13-acetate (PMA) in 1982, a lot of methods of culturing were tried but till date PMA is a preferred mitogen because of its cost effectiveness compared to growth factors. We have tried to preliminarily evaluate the efficacy of another phorbol ester, Phorbol 12, 13-dibutyrate (PDBu) in melanocyte culture because of its less hydrophobic nature compared to PMA. This property minimizes the trace amount of mitogen in cell culture after washing off and hence does not interfere in other biological assays. AIM: To evaluate the differences in the melanocyte survival rate, morphology and mitotic index when grown in media supplemented with PMA and PDBu. MATERIALS AND METHODS: Foreskins were collected from children undergoing circumcision. Epidermal cells were isolated from foreskin and cultured using PMA and PDBu. Melanocytes in culture were monitored for the better establishment and documented. In proliferative assay, melanocytes were treated with PMA and PDBu for 24, 48 and 72 hours and proliferation was measured using 3-(4,5 Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay method. RESULTS: When cultured, melanocytes acquired proliferative status and bipolar morphology quicker in PDBu medium than in PMA medium. Keratinocytes survived as contamination in PMA medium whereas PDBu medium had minimal keratinocytes. MTT assay showed that PDBu has higher proliferative induction capacity than PMA. In even lower concentration of PDBu in medium, melanocytes survived till 72 hours without significant cell loss in compared to PMA medium. CONCLUSION: PDBu can be a valuable replacement for PMA in human melanocyte culture. Higher proliferation induction, unfavourable to keratinocyte survival and less hydrophobicity make PDBu a promising alternative for quicker establishment of pure human melanocyte cultures especially in cosmetic in vitro experimental dermatology. PMID- 26894088 TI - Skill Learning Through Early Clinical Exposure: An Experience of Indian Medical School. AB - INTRODUCTION: Indian Medical curriculum being discipline based, there is a line of demarcation between preclinical and clinical subjects. The challenges in medical education include the methods that would enhance the clinical education quality; one such method been Early Clinical Exposure (ECE). ECE can help to instill the skill component of medical education in the first year students helping to minimize the line of demarcation. Hence this study was undertaken to assess the skill learning of students through early clinical exposure and to collate the perception of them. MATERIALS AND METHODS: In the present study, students of 1(st) MBBS were exposed to ECE as an adjunct teaching method with preset modules. They were evaluated by Objectively Structured Clinical Examination (OSCE). Feedback was obtained from 1(st) MBBS and also from the same students after passing the 1(st) MBBS in 4(th) semester. RESULTS: Significant differences in pre and post OSCE scores were noted (p<0.0001). Seventy six percent students rated ECE as an excellent tool. Second year students also perceived ECE held in 1(st) year was helpful to correlate topics and increasing confidence. CONCLUSION: ECE had an effective influence on learning as manifested in skills gained by the students and their perceptions of ECE being helpful prospectively in their routine clinical posting. PMID- 26894089 TI - Using Movies to Strengthen Learning of the Humanistic Aspects of Medicine. AB - INTRODUCTION: Movie screening and activities have been used during the last two semesters (spring and summer 2015) to strengthen the learning of communication skills, empathy, professionalism, and greater understanding of the process and death and dying at the Xavier University School of Medicine. AIM: The present manuscript describes the movie screening and activities. Student feedback regarding the sessions is also mentioned. SETTINGS AND DESIGN: The activity was conducted among basic science undergraduate medical students and student feedback was obtained. A cross-sectional study design was used. MATERIALS AND METHODS: Feedback was obtained towards the end of June 2015 using a questionnaire designed by the authors. Participants were asked to rate their degree of agreement with the set of statements and provide an overall rating for the sessions. No demographic information was collected. STATISTICAL ANALYSIS: Cronbach's alpha was calculated as a measure of internal consistency. The normality of distribution of the scores of individual statements and of the overall rating was determined using one sample Kolmogorov-Smirnov test. The average scores were calculated. Free text comments were tabulated. RESULTS: Forty-nine of the 63 students (77.8%) participated in the study. Cronbach's alpha was 0.868 indicating a high level of internal consistency. The median scores indicating the degree of agreement with most statements ranged from 3 to 5. The mean participant rating of the sessions was 7.10 (maximum possible score 10). A few participants provided free text comments regarding the sessions. CONCLUSION: Student feedback about the session was positive. Impact of the session on humanistic issues, professionalism and death and dying should be studied in future. PMID- 26894090 TI - Comparison of Flow and Volume Incentive Spirometry on Pulmonary Function and Exercise Tolerance in Open Abdominal Surgery: A Randomized Clinical Trial. AB - INTRODUCTION: Surgical procedures in abdominal area lead to changes in pulmonary function, respiratory mechanics and impaired physical capacity leading to postoperative pulmonary complications, which can affect up to 80% of upper abdominal surgery. AIM: To evaluate the effects of flow and volume incentive spirometry on pulmonary function and exercise tolerance in patients undergoing open abdominal surgery. MATERIALS AND METHODS: A randomized clinical trial was conducted in a hospital of Mangalore city in Southern India. Thirty-seven males and thirteen females who were undergoing abdominal surgeries were included and allocated into flow and volume incentive spirometry groups by block randomization. All subjects underwent evaluations of pulmonary function with measurement of Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1), Peak Expiratory Flow (PEF). Preoperative and postoperative measurements were taken up to day 5 for both groups. Exercise tolerance measured by Six- Minute Walk Test during preoperative period and measured again at the time of discharge for both groups. Pulmonary function was analysed by post-hoc analysis and carried out using Bonferroni's 't'-test. Exercise tolerance was analysed by Paired 'T'-test. RESULTS: Pulmonary function (FVC, FEV1, and PEFR) was found to be significantly decreased in 1(st), 2(nd) and 3(rd) postoperative day when compared with preoperative day. On 4(th) and 5(th) postoperative day the pulmonary function (FVC, FEV1, and PEFR) was found to be better preserved in both flow and volume incentive spirometry groups. The Six-Minute Walk Test showed a statistically significant improvement in pulmonary function on the day of discharge than in the preoperative period. In terms of distance covered, the volume- incentive spirometry group showed a greater statistically significant improvement from the preoperative period to the time of discharge than was exhibited by the flow incentive spirometry group. CONCLUSION: Flow and volume incentive spirometry can be safely recommended to patients undergoing open abdominal surgery as there have been no adverse events recorded. Also, these led to a demonstrable improvement in pulmonary function and exercise tolerance. PMID- 26894092 TI - A Cross Sectional Study on Acceptability and Safety of IUCD among Postpartum Mothers at Tertiary Care Hospital, Telangana. AB - INTRODUCTION: India is world's 2(nd) largest populated country. It is first to introduce family planning services. IUCD is most effective, safe, long acting and do not interfere with coitus. Immediately or within 72 hours after delivery of placenta in a health care facility is convenient for those who are in outreach area, where family planning facilities are less available. OBJECTIVES: To study the socio demographic profile of parturients attended to obstetric ward for delivery. To assess the acceptability and safety of IUCD among study population. MATERIALS AND METHODS: A cross-sectional study was conducted among eligible postpartum women at Gandhi hospital secunderabad. Counseling was given about IUCD. After obtaining consent, Cu-T 380 was inserted in a 250 women, followed up to 6 weeks. The reasons for both acceptance and decline were recorded. RESULTS: Mean age of acceptance was 23.70+/-2.95 years. Majority were from urban area (79.75%). Acceptance was more in those who completed their secondary school level education (23.3%). Women undergoing caesarean section were accepting PPIUCD, more frequently than those who underwent normal vaginal delivery. Majority (67.12%) accepters told that they accepted IUCD because it is a reversible method. Main reported complications were pain abdomen (17.14%), bleeding (14.28%). Expulsion rate was 6.8%. Most common reason (40%) for removal of IUCD was inclination to other methods. CONCLUSION: Even though expulsion rate high with, acceptance was high IUCD when it is inserted in postpartum period. PMID- 26894091 TI - Reliability and Validity of Standing Back Extension Test for Detecting Motor Control Impairment in Subjects with Low Back Pain. AB - INTRODUCTION: Low back pain is a chronic health problem with high socioeconomic impact. Specific diagnosis or treatment approach has not yet effectively established to treat chronic low back pain. Standing Back Extension Test is one of the clinical measures to detect the passive extension subgroup of Motor Control Impairment (MCI); which could have an impact on spinal stability leading to recurrent chronic low back pain. Reliability and validity of this test is not fully established. AIM: To determine the intra-rater and inter-rater reliability and concurrent validity of the Standing Back Extension Test for detecting MCI of the lumbar spine. MATERIALS AND METHODS: A total of 50 subjects were included in the study, 25 patients with Non Specific Low Back Pain (NSLBP) (12 men, 13 women) and 25 healthy controls (12 men, 13 women) were recruited into the study. All subjects performed the test movement. Two raters blinded to the subjects rated the test performance as either 'Positive' or 'Negative' based on the predetermined rating protocol. The thickness of Transverse Abdominis (TrA) muscle was assessed using Rehabilitative Ultrasound Imaging (RUSI). STATISTICAL TEST USED: For reliability, the kappa coefficient with percent agreement was calculated and for assessing the validity Receiver Operator Characteristic (ROC) curves and Area under the Curve (AUC) were constructed. RESULTS: The standing back extension test showed very good intra-rater (k=0.87 with an agreement of 96%) and good inter-rater (k=0.78 with an agreement of 94%) reliability and high AUC for TrA muscle. CONCLUSION: The standing back extension test was found to be a reliable and a valid measure to detect passive extension subgroup for MCI in subjects with low back pain. PMID- 26894093 TI - Determination of Prevalence of Type 2 Diabetes Mellitus by Screening Tests using a Mathematical Formula in Place of Invasive Blood Tests. AB - INTRODUCTION: True prevalence rate of diabetes mellitus in a population can be obtained by using invasive tests but it is practically difficult on large scale. AIM: To find out the feasibility of mass non-invasive screening test to detect the prevalence of diabetes mellitus in rural population of India with the help of a mathematical formula. MATERIALS AND METHODS: From population of 18800 residing in two adjacent rural areas of Delhi, a systematic random sample of 1005 adult subjects was screened for diabetes by using urine benedicts test, Canrisk questionnaire, Madras Diabetes Research Foundation-Indian Diabetic Risk Score (MDRF-IDRS) and determined prevalence of diabetes (pA) gauzed by each of these screening tests. Simultaneously, each subject's glycaemic status was confirmed by standard fasting Plasma glucose (FPG) and postprandial plasma glucose (PPPG) levels. The blood test was also used to determine true prevalence which was cross checked with the prevalence estimated (Pe) by the above stated screening tests using a mathematical formula. RESULTS: The true prevalence of T2DM in more than 18 years of population by Fasting Plasma Sugar (FPS) was 4.5% while that by using mathematical formulae that estimated by urine test, Canrisk test and MDRF-IDRS was 4.4%, 4.4 and 4.3% respectively. When more than 35 years age-group was selected, true prevalence was 7.4% and estimated prevalence by Canrisk test was 7.1% (as against gold standard of Fasting) and 6.9% (as against PP). By fasting urine test it came out to be 7.2% and by PP urine test it was 7.4%. In population l8-35 years, the prevalence of diabetes was 1.1% by plasma glucose test. By using Canrisk, it came out to be 1.04%. CONCLUSION: Individual screening tests such as urine, Canrisk and MDRF-IDRS can be used to estimate prevalence rates of diabetes in rural areas by means of mathematical formula which would be close to true estimates. PMID- 26894094 TI - Application of WHO 'Near-Miss' Tool Indicates Good Quality of Maternal Care in Rural Healthcare Setting in Uttarakhand, Northern India. AB - INTRODUCTION: Women who experienced and survived a severe health condition during pregnancy, childbirth or postpartum are considered as 'near-miss' or severe acute maternal morbidity (SAMM) cases. Women who survive life-threatening conditions arising from complications related to pregnancy and childbirth have many common aspects with those who die of such complications. AIM: To evaluate health-care facility preparedness and perfor-mance in reducing severe maternal out comes at all levels of health care. MATERIALS AND METHODS: The present study was carried out over a period of 12 months under the Department of Community Medicine. The cross-sectional study included all the women (937) attending health-care facilities, at all levels of health care i.e. Primary, Secondary & Tertiary level in Doiwala block of Dehradun district. This study was conducted as per the WHO criteria for 'near-miss' by using probability sampling for random selection of health facilities. All eligible study subjects visiting health-care facilities during the study period were included, i.e. who were pregnant, in labour, or who had delivered or aborted up to 42 days ago. RESULTS: It was found that all women delivering at the THC received oxytocin to prevent postpartum haemorrhage. Treatment of severe post-partum haemorrhage by removal of retained products was significantly associated with levels of health care. Majority (94.73%) women who had eclampsia received magnesium sulfate as primary treatment. CONCLUSION: Application of WHO 'near-miss' tool indicates good quality of maternal care in rural healthcare setting in Uttarakhand, North India. The women would have otherwise died due to obstetrics complications, had proper care not been provided to them in time. PMID- 26894095 TI - Mobile Phone Usage and its Health Effects Among Adults in a Semi-Urban Area of Southern India. AB - INTRODUCTION: Worldwide, mobile phone usage has been increased dramatically which could affect the health of the people. India has the second largest number of mobile phone users. However there are only few studies conducted in India to assess its effects on health. AIM: To determine the prevalence and pattern of mobile phone usage and to assess the relationship between certain selected health problems and mobile phone usage among adults. SETTINGS AND DESIGN: Community based cross-sectional study was conducted in Kottakuppam, a town panchayat in Villupuram district of Coastal Tamil Nadu, Southern India. It is a semi-urban area with a population of about 16,000. Majority of the residents are Muslim by religion and belong to different socio economic status. MATERIALS AND METHODS: The study was approved by the Institutional Ethics Committee. A total of 2121 study participants were interviewed by the pre-final medical students through house-to-house survey using a pretested structured questionnaire. The questionnaire included the variables such as socio demographic profile, mobile phone usage and pattern, selected health problems, perceived benefits and threats and blood pressure. Selected health problems included headache, earache, neck pain, tinnitus, painful fingers, restlessness, morning tiredness, tingling fingers, fatigue, eye symptoms, sleep disturbance and hypertension. STATISTICAL ANALYSIS USED: Only 2054 were included for data analysis using SPSS 17 version. Proportions were calculated. Chi-square test was used to measure the p-value. The p-value < 0.05 was considered as statistically significant. RESULTS: The prevalence of mobile phone usage was 70%. Calling facility (94.2%) was used more than the SMS (67.6%). Health problems like headache, earache, tinnitus, painful fingers and restlessness etc., were found to be positively associated with mobile phone usage. There was negative association between hypertension and mobile phone usage. CONCLUSION: The prevalence of mobile phone usage was high. There was significant association between selected health problems and mobile phone usage. In future, higher studies are required to confirm our findings. PMID- 26894096 TI - Prevalence of Anaemia among Postnatal Mothers in Coastal Karnataka. AB - INTRODUCTION: Postpartum is the most neglected period in reproductive cycle of woman. Prevalence of anaemia in developing countries ranges from 50-95%. AIM: To estimate the prevalence of anaemia among postnatal mothers. SETTING AND DESIGN: A community based cross-sectional study among recently delivered mothers residing in field practice area of Department of Community Medicine, Kasturba Medical College, Manipal, India. MATERIALS AND METHODS: The study sample included 401 respondents who were selected using stratified random sampling with proportionate allocation from all rural health centres. Data was collected by personal interviews followed by haemoglobin estimation by indirect cyanomethaemoglobin method. RESULTS: The prevalence of postnatal anaemia was 26.5% (Anaemia = Hb<12gm/dl). There were no cases of severe anaemia. Postnatal anaemia was predominantly seen in mothers of age < 20 years and half of the mothers with inter-pregnancy intervals less than two years were found to be anaemic. Illiteracy was identified as a significant variable (OR=11.23, 95% CI = 1.90 65.08) for postpartum anaemia. CONCLUSION: The prevalence of anaemia was significantly lower in the present study; however sustained efforts have to be made to further lower the prevalence of postnatal anaemia in order to promote the health and well-being of women. PMID- 26894097 TI - Safe Injection Practices in Primary Health Care Settings of Naxalbari Block, Darjeeling District, West Bengal. AB - INTRODUCTION: Unsafe injection can transmit many diseases to patients, injection providers and healthy people of community. AIM: To find out critical steps whether executed according to recommended best practice methods, availability of equipments in health facilities for safe injection practices and some important steps of waste disposal methods. MATERIALS AND METHODS: This facility-based cross sectional observational study was conducted among 30 Auxiliary nurse midwives (ANM) & 27 nursing staffs (NS) to assess certain aspects of their practice while administrating injection and disposal of the disposables. Health facilities were also observed to asses necessary equipments of safe injection and waste disposal methods. RESULTS: Among the health workers 93.3% ANM and 100% NS took sterile syringe from sterile unopened packet, all of the study subjects washed hand before giving injection, 13.3% of ANMs and 8% of NS are fully vaccinated against Hep B, 53.3% of ANM and all NS are practices non recapping. Only 13.33% sub centres along with PHC & BPHC had at least one puncture resistant leak proof container, 86.7% sub centres, PHC are free from loose needles. Transport for off side treatment is the method of waste disposal in case of 73.3% cases sub centres, PHC & BPHC. CONCLUSION: There is need to educate, train and motivate service providers in proper methods of giving injection along with improve the adequacy of supply of required equipments. PMID- 26894098 TI - Spectral Analysis of Hypernasality in Cleft Palate Children: A Pre-Post Surgery Comparison. AB - INTRODUCTION: Change in resonance is the most commonly experienced speech problems in children diagnosed with cleft lip and palate. The degree of nasality during normal speech production is maintained by the changes in velopharyngeal port. These variations in speech signal are reported to be successfully captured using acoustical tools like spectral analysis. AIM: The present study investigated to note voice low tone to high tone ratio (VLHR) values for phonation samples of individuals with cleft palate before and after surgery. MATERIALS AND METHODS: Thirty children with congenital cleft of palate within 8 to 15 years of age participated in the study. Three trials of sustained vowels (/a/,/i/ and /u/) were recorded at their comfortable pitch and loudness level in a noise free room using a hand held dynamic microphone. Praat software that utilized Hillenbrand algorithm was used to extract the VLHR values for samples recorded before and after recovery from the surgery. RESULTS: Statistical analysis revealed significant decrease in VLHR values after surgery in comparison to before the surgery. Analysis of Variance revealed statistical significant difference at 95% confidence level. CONCLUSION: It is concluded that VLHR parameter could be used as an index to measure nasality and can be included in the routine tool assessment protocol. PMID- 26894099 TI - Head and Neck Tuberculosis: Scenario in a Tertiary Care Hospital of North Eastern India. AB - INTRODUCTION: Tuberculosis has affected mankind since time immemorial and with emergence of AIDS both extrapulmonary and pulmonary tuberculosis presents increased morbidity and mortality along with an increased financial burden upon the developing nations. MATERIALS AND METHODS: The study is a hospital based observational study of one year duration carried out in the Department of ENT in a tertiary care hospital of North Eastern India. RESULTS: Total of 63 cases were detected. Females comprised 60.3% of the study population as against 39.7% males. Most commonly affected age group were of 15 to 24 years age (57.1%). Cervical tubercular lymphadenitis was the most common lesion 90.5% (57 cases) followed by laryngeal tuberculosis 7.9% (5 cases) and tubercular otitis media with mastoiditis 1.6% (1 case). Level II lymph node was mostly affected either single or in groups (75.4%) followed by level III node (57.9%). Successful outcome of the treatment with Category I regimen was achieved in 96.8% of the cases. CONCLUSION: Head and neck tuberculosis is not an uncommon disease and though cervical lymphadenitis is the most common presentation, isolated involvement of the larynx, ear and other subsites are not an entirely unknown entity. The clinical presentation of tuberculosis of the head and neck region can be varied and often misleading. It is therefore important for the clinician to be aware of the condition and consider it in their differential diagnosis. PMID- 26894100 TI - A Hospital Based Study Regarding Awareness of Association Between Glycosylated Haemoglobin and Severity of Diabetic Retinopathy in Type 2 Diabetic Individuals. AB - INTRODUCTION: Diabetic retinopathy is one of the most common microvascular complications seen in diabetic patients after a long term of uncontrolled glycaemic status as assessed by glycosylated Haemoglobin A (HbA1c). Hence awareness of glycaemic control is necessary to prevent vision threatening complications. AIM: To assess the awareness regarding association between glycosylated Haemoglobin (HbA1c) and diabetic retinopathy among diabetic patients and to assess the impact of lack of this knowledge on the severity of diabetic retinopathy (DR). MATERIALS AND METHODS: This hospital based cross-sectional study was conducted in the ophthalmology OPD on 200 adult diabetic patients, between November 2012 and January 2013, who were assessed for their knowledge regarding association between HbA1c and its impact on the progress of DR. The study was done with the help of a semi structured questionnaire which included demographic details, literacy levels, diabetic status and awareness of HbA1c. STATISTICS USED: Cochran Armitage test for trend, Fisher Exact test, chi-square for trend and Student's t test. RESULTS: Among the 200 diabetic individuals attending our OPD, 180 (90%) were aware of the importance of blood sugar levels and its fluctuation in type 2 diabetes. Only 23 (11.5%) were aware of HbA1c whereas 10 (5%) misinterpreted it as levels of haemoglobin, 3 (1.5%) did not completely comprehend. About 164 (82%) patients were not aware of the significance or the terminology of HbA1c. Out of the 200 patients, 58 patients showed presence of some grade of DR. Amongst these 58 patients, 7(12.1%) were aware of HbA1c and all the11 patients with clinically significant macular oedema (CSME) were aware of the risk factors of elevated blood sugar levels but ignorant of HbA1c. Among the remaining 142 individuals who showed no signs of DR, 16 (27.5%) were aware of and comprehended the role of HbA1c. CONCLUSION: Our study highlights the gross ignorance of role of HbA1c in the progress of DR among diabetic individuals. It is a known fact that the risk of DR reduces by 35% for every 1% reduction in HbA1c. Hence a strict control of blood sugar level with regular monitoring of HbA1c can help diabetic individuals in prevention of progress of DR, thus preventing severe vision loss. PMID- 26894102 TI - Orbital Metastasis of Cervical Carcinoma - Case Report and Review of Literature. AB - The orbit is a frequent site of metastasis, particularly from the breast, prostate gland and the lung. Carcinoma of the cervix metastasizing to the orbit is rare. We report a 27-year-old woman with Stage II B cervical cancer who presented with progressive painless protrusion of the left eye of one month duration associated with diplopia. Histology of the orbital mass was similar to that of the cervical cancer and reported as squamous cell carcinoma. She received palliative radiation to the left orbit 30 Gy in 10 fractions along with chemotherapy (Paclitaxel and Carboplatin). This resulted in regression of the proptosis. We review published literature of cases of carcinoma of the uterine cervix with metastasis to the orbit. PMID- 26894101 TI - Visual Outcome of Traumatic Cataract at a Tertiary Eye Care Centre in North India: A Prospective Study. AB - INTRODUCTION: One of the most common presentations of blunt and penetrating ocular trauma is traumatic cataract. It remains a significant cause of visual impairment and physical disability among adults and children. It is associated with various ocular injuries. AIM: To evaluate the associated ocular injuries and final outcome of patients with traumatic cataract along with their demographic features and modes of trauma. MATERIALS AND METHODS: A prospective study done in Department of Ophthalmology in M.L.B. Medical college, Jhansi from February 2010 to July 2011. A total of 48 patients diagnosed as a case of traumatic cataract were subjected to a detailed history, systemic and local examination with relevant investigations. Medical or surgical managements were done accordingly. Patients were subsequently followed-up and visual acuity was recorded. Appropriate statistical tests were applied. RESULTS: A 54.2% patients sustained penetrating trauma while 45.8% got blunt injury. Out of total, 79% patients were males while 50% were less than 15 years of age. Causative agents were stone, wood items, stick, metal objects etc. Among blunt trauma cases, 64% of the patients had visual acuity <6/60 while among penetrating trauma cases nobody had acuity >6/18. Anterior segment was more involved as compared to posterior segment. A 38.5% patients had corneal opacity among penetrating injury patients. The interval between trauma and surgery was less than one month among 75% of patients. After three months of surgery, 43.7% patients had visual acuity of >6/18. CONCLUSION: This study provides recent data of patients hospitalized after ocular trauma and diagnosed as a case of traumatic cataract. Traumatic cataract occurs mostly in younger males. Surgical intervention is necessary to improve visual outcome. Good visual outcome was obtained in nearly half of the patients. Traumatic cataract patients can have good visual outcome depending upon proper management. PMID- 26894103 TI - Granulocytic Sarcoma in an Adult with Relapsed Acute Myeloid Leukaemia. AB - Granulocytic sarcoma is an extramedullary tumour consisting of malignant granulocytic precursor cells that is common among children with acute myeloid leukaemia (AML). We report a case of orbital granulocytic sarcoma in an adult with relapsed undifferentiated AML-M0. It presented as bilateral medial canthal swellings. An incisional biopsy confirmed the diagnosis of granulocytic sarcoma. The swelling resolved with re-induction chemotherapy. PMID- 26894104 TI - A Comparative Study of Pre and Post-prandial BP Recordings in Obese and Non Obese Young Adults. AB - INTRODUCTION: Obesity is associated with varied combinations of abnormalities in the autonomic nervous system. Studies have shown that obese people who have a higher sympathetic tone have higher catecholamine levels. This can predispose to arythmogenesis and sudden death. AIM: To study pre and post-prandial BP recordings in obese and non obese young adults in the age group of 18 to 45 years. MATERIALS AND METHODS: The study was conducted on 50 obese and 50 non obese patients admitted to our hospital over a period of three months. The patients are randomly selected and the BMI is calculated. Both systolic and diastolic blood pressure is measured in supine position of the right arm using digital electronic blood pressure monitor. BP recordings are taken 30 minutes before and 30 minutes after meals. Then fall in BP is recorded. RESULTS: From this study we found that the mean systolic (pre-prandial 124.36, post-prandial 116.6) and diastolic blood pressure (pre-prandial 78.8 and post-prandial 75.4) is higher in obese than non obese patients. The study was statistically significant which was found by paired t-test (p<0.05). CONCLUSION: The fall in BP was significantly higher in obese (12 patients out of 50) than non obese (5 patients out of 50) patients. Probably obese patients had reduced cardiac sympathetic tone which caused post-prandial hypotension more than non obese patients. PMID- 26894105 TI - Study of Adverse Effect Profile of Parenteral Zoledronic Acid in Female Patients with Osteoporosis. AB - INTRODUCTION: Osteoporosis is still a under recognized entity in the population. Osteoporosis-related fractures can be prevented if people at risk can be screened, diagnosed and treated early. Bisphosphonates remain the mainstay of osteoporosis treatment as they have multimodal action. Oral bisphosphonate therapy has, significant gastrointestinal side effects leading to noncompliance. Of late parenteral Zoledronic Acid is being used as once or twice yearly infusion for the treatment of osteoporosis. AIM: Our article studies the side effect profile and tolerability of parenteral Zoledronic Acid, one of the most potent bisphosphonate used in clinical practice in patients with osteoporosis. MATERIALS AND METHODS: This study was done in KMC hospitals where 49 patients diagnosed with osteoporosis were included for the study. After obtaining a written informed consent each patient received one infusion of 5 mg Zoledronic Acid as per standard treatment protocol. Patient was monitored for clinical improvement and development of any adverse effects. CONCLUSION: In our study all subjects reported significant pain relief after infusion of Zoledronic Acid. Zoledronic Acid had very few serious adverse effects that can be prevented through pre infusion screening, maintaining good hydration and careful patient monitoring. In our population the patients only experienced mild symptoms of pyrexia, arthralgia myalgia and influenza like symptoms which resolved with symptomatic treatment. PMID- 26894106 TI - A Study on the Role of Heart Type Fatty Acid Binding Protein in the Diagnosis of Acute Myocardial Infarction. AB - INTRODUCTION: Heart type Fatty Acid Binding Protein (H-FABP) has been proposed as an early cardiac biomarker for the diagnosis of acute myocardial Infarction (AMI) using animal models and clinical samples. AIM: The study aimed to evaluate the role of H-FABP in early detection of AMI by comparing its sensitivity, specificity and predictive value with Creatinine Kinase-MB (CK-MB) and Cardiac Troponin I (cTnI). MATERIALS AND METHODS: This is a cross-sectional descriptive study of 50 patients admitted with the diagnosis of AMI at a tertiary care hospital in South India. The study group was categorised in to those coming to the hospital within four hours of symptom onset and those coming in between 4 to 12 hours. H-FABP was compared with those of troponin T and myoglobin tests. RESULTS: Among patients presenting within four hours of symptom onset, the sensitivity of H-FABP was 60% and was significantly higher than that of cardiac Troponin I (cTnI, 18.8%) and Creatinine Kinase (CK)-MB (12.5%). But specificity was only 23.53% and was less than that of cTnI (66.67%) and CK-MB (100%). In patients presenting during 4 to 12 hours of symptom onset, the sensitivity of H FABP was 86.96% which was comparable to that of cTnI (90.9%) and CK-MB (77.3%). The specificity was 60% in the 4-12 hours group which was comparable to that of cTnI (50%) and CK-MB (50%). CONCLUSION: The H-FABP is a sensitive biomarker for the diagnosis of AMI in the initial hours after symptom onset when the standard biomarkers may not be elevated, but it is less specific. During 4-12 hours of symptom onset it is as sensitive and specific as standard cardiac biomarkers troponin and CK-MB. Due to these factors H-FABP can be considered as a promising cardiac biomarker which can be used along with troponins and CK-MB at present. PMID- 26894107 TI - Prescribing Pattern of Oral Antihyperglycaemic Drugs, Rationality and Adherence to American Diabetes Association (ADA) Treatment Guidelines among Type 2 Diabetes Mellitus (T2DM) Postmenopausal Women. AB - INTRODUCTION: Oral antihyperglycaemic prescription trends keep on changing and thus the drug prescription trend study may prove to be powerful exploratory tool for health care providers. AIM: To investigate trends in prescriptions of oral antihyperglycaemic drugs (OHDs) among postmenopausal women suffering from T2DM in India and evaluate the rationality and adherence to ADA treatment guidelines. MATERIALS AND METHODS: An observational, cross-sectional descriptive prescription audit (n=500) was carried. Postmenopausal women were interviewed in their local language using pre-tested pre validated questionnaire after verbal informed consent at a teaching tertiary care hospital of north India. Oral antihyperglycaemic drugs (OHDs) drugs were categorized as per the pharmacological classification. Adherence to available clinical practice guidelines/recommendations issued under American Diabetes Association (ADA) 2015 Guidelines as well as rationality of these prescriptions were assessed using WHO Guide to Good Prescribing. RESULTS: Mean age of the study population was 58.14+/ 12.86. Mean duration since menopause was 5.3 years and of T2DM was 9.5 years. A 93.4% of the prescriptions had only OHDs whereas 6.6% of the prescriptions had various insulin preprations + OHDs (p<0.0001). Biguanides followed by sulfonylureas, thiazolidinediones, DPP-inhibitors and alpha-glucosidases inhibitor were prescribed in 85.6%, 59.8%, 26.6%, 26% and 12.2% respectively as monotherapy or in combination. Among biguanides, metformin was the most frequently prescribed OHDs. In spite of black box warning on pioglitazone, it was prescribed in 26.6% as FDC. However, clear increase use of vidagliptine was noticed upto 26%. Among combinations most frequent was metformin plus glimipride followed by voglibose plus metformin, whereas, among FDC, metformin plus glimipride followed by metformin plus vidagliptine were most frequently prescribed. CONCLUSION: Metformin was the most common OHDs to be prescribed followed by glimepiride. Although pioglitazone still continues to be prescribed after safety alert but apparently it appears that the share of pioglitazone has been shifted to vidagliptin or combinations like metformin plus glimipride. Polypharmacy, high use of FDC, & prescription by brand names were some of the irrationalities. Relatively low adherence to ADA treatment guidelines was observed. PMID- 26894108 TI - Relation between Vitamin D Deficiency and Severity of Chronic Obstructive Pulmonary Disease-A Case Control Study. AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by irreversible and progressive limitation of expiratory airflow. COPD is now considered as a systemic disease with several extra-pulmonary manifestations which include osteoporosis, muscle weakness, arrhythmia, stroke, cancer etc. The role of vitamin D in skeletal integrity is well established. Role of it in several other diseases like autoimmune, infectious, respiratory and cardiovascular diseases has been increasingly recognised. Data on vitamin D status in COPD in Indian population was limited while those comparing vitamin D with stage, pack year and body mass index were lacking. AIM: To assess Vitamin D in subjects with COPD and matched controls and also to study the variability in serum vitamin D levels with COPD disease characteristics. MATERIALS AND METHODS: A total of 162 patients aged 18-65 years from south India presenting to kasturba hospital were included in the study. Serum 25- hydroxy-vitamin D were measured in 81 COPD patients (combined COPD stage A-D) and compared with 81 age and gender matched controls. Level < 20 ng/ml defined deficiency. Risk estimate with Odds ratio and association of COPD characteristics with Vitamin D was assessed using logistic regression analysis. RESULTS: COPD patients had an increased risk for vitamin D deficiency compared to controls after adjustment for age and gender(OR =2.687 (1.40,5.13)). Variables associated with lower 25(OH) D levels in COPD patients were higher pack year (p=0.001), current smoking status (p=0.026), Low BMI (p=0.02), and GOLD stage III IV (p=0.001). CONCLUSION: COPD was associated with an increased risk of vitamin D deficiency, and there was a significant association between vitamin D levels and Combined COPD stage severity. Also, a higher pack year and a low BMI are associated with lower levels of vitamin D. PMID- 26894109 TI - Lady Windermere Syndrome: A Very Rare Entity In Indian Medical Scenario. AB - Bronchiectasis is a common respiratory disorder, which we come across in clinical practice. Patients with bronchiectasis are prone to infections, especially of Mycobacterium tuberculosis. However, non-tubercular Mycobacterial infections may also set in, though rare. Here, we report an unusual case of Mycobacterium avium complex infection in a case of middle lobe bronchiectasis that was seen in a middle-aged immunocompetent female, a syndrome known as Lady Windermere Syndrome. PMID- 26894110 TI - A Rare Presentation of Lupus Nephritis Flare up with Posterior Reversible Leucoencephalopathy. AB - Systemic lupus erythematosus (SLE) is associated with various neurologic or psychiatric abnormalities and Posterior Reversible Leuco Encephalopathy Syndrome (PRES) is very rare neurological manifestation in SLE. PRES is associated with various clinical manifestations, like, seizures, visual loss, headaches, vomiting altered mental status and rarely focal neurological deficits. Other predisposing condition associated with PRES is eclampsia, accelerated hypertension, uraemia, transplantation, autoimmune diseases and/or use of immunosuppressive drugs. It is important to recognise PRES since it is a potentially reversible. We describe an unusual case of PRES caused by uraemia during lupus flare up in a patient with biopsy proven class IV lupus nephritis who presented with features of asymmetrical quadriparesis which completely reversed after haemodialysis sessions and treating lupus flare up. In our case she presented with quadriparesis which is a rare presentation and hypertensive encephalopathy was not present. PMID- 26894111 TI - Spontaneous Subdural Haemorrhage: A Rare Association with Plasmodium Vivax Malaria. AB - Malaria is an endemic disease in tropical countries and disease of universal importance. Central Nervous System (CNS) complications of malaria are severe and associated with significant mortality. Thrombocytopaenia in malaria causing haemorrhagic CNS complications is rare. We report a case of 35-year-old male patient presented with headache, vomiting and was diagnosed to have subdural haemorrhage (SDH). On examination patient was found to be febrile with peripheral smear showing evidence of Plasmodium vivax (P.vivax) infection with severe thrombocytopaenia. In endemic regions with malaria, SDH being rare presentation of malaria should be considered as a differential diagnosis in febrile patients with neurological manifestations. Rarity of spontaneous SDH in malaria and raising awareness amongst treating physicians about the same is the driving factor for reporting this case. PMID- 26894112 TI - A Rare Case of Sporadic Inclusion Body Myositis (s-IBM). AB - Sporadic inclusion body myositis (s-IBM) is an acquired inflammatory myopathy. Clinical presentation is variable. The usual presentation is progressive weakness and atrophy of the arms and leg muscles, especially of the quadriceps femoris which is invariably affected. It is classified under inflammatory myopathies, along with polymyositis and dermatomyositis. We present a case of s-IBM who presented with gradually progressive quadriparesis with characteristic quadriceps wasting and weakness in neck flexors. Electromyography revealed myopathic potential and muscle biopsy revealed features of inclusion body myositis. PMID- 26894113 TI - Severe Hypokalaemia, Hypertension, and Intestinal Perforation in Ectopic Adrenocorticotropic Hormone Syndrome. AB - Ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of the Cushing's syndrome. The occurrence of the ectopic ACTH syndrome presenting with severe hypokalaemia, metabolic alkalosis, and hypertension has been highlighted in case reports. However, presentation with lower gastrointestinal perforation is not known. We report the case of a 70-year-old male patient with severe hypokalaemia, metabolic alkalosis, hypertension, and colonic perforation as manifestations of an ACTH-secreting small cell lung carcinoma. Ectopic ACTH syndrome should be kept in mind as a cause of hypokalaemia, hypertension, and intestinal perforation in patients with lung carcinoma. PMID- 26894114 TI - Typhoid Fever, Below the Belt. AB - Genital ulcers occur due to infective, inflammatory, malignant and drug-related causes. In tropical countries such as India, such ulcers are due to parasitic, tubercular, rickettsial and bacterial (sexually transmitted infections) aetiologies. Typhoid fever is endemic in the tropics. Except "rose spots", skin manifestations in typhoid fever are unusual, and they are missed due to pigmented skin. Patients do not often complain of genital ulcers due to shame or fear. Genital examination is not routinely performed in typhoid fever. We describe scrotal ulcers as the presenting symptom of typhoid fever, which subsided with appropriate therapy. PMID- 26894115 TI - Hypokalaemic Periodic Paralysis in a Patient with Subclinical Hyperthyroidism: A Rare Case. AB - Thyrotoxic Periodic Paralysis (TPP) is an uncommon disorder. Though many cases of hypokalaemic periodic paralysis are reported in overt hyperthyroidism, hypokalaemic paralysis in subclinical hyperthyroidism is very rare. Subclinical hyperthyroidism is characterised by circulating TSH levels below reference range and normal thyroid hormone levels. We describe a case of 32-year-old Asian male who presented to the emergency department with acute onset weakness and hypokalaemia with no previous history of thyroid disorder or any signs and symptoms suggestive of hyperthyroidism. He was subsequently diagnosed with Graves' disease with subclinical hyperthyroidism. PMID- 26894117 TI - Acute Pancreatitis in a Patient with Complicated Falciparum Malaria. AB - Malaria is one of the most common protozoan diseases, especially in tropical countries. The clinical manifestation of malaria, especially falciparum malaria varies from mild acute febrile illness to life threatening severe systemic complications involving one or more organ systems. We would like to report a case of complicated falciparum malaria involving cerebral, renal, hepatic system along with acute pancreatitis. The patient was successfully treated with anti malarial and other supportive treatment. To the best of our knowledge there are very few reports of acute pancreatitis due to malaria. Falciparum malaria therefore should be added to the list of infectious agents causing acute pancreatitis especially in areas where malaria is endemic. PMID- 26894116 TI - Hypersensitivity Pneumonitis in a Housewife Exposed to Aspergillus flavus in Poor Living Conditions: A Case Report. AB - Hypersensitivity Pneumonitis (HP) or Extrinsic Allergic Alveolitis (EAA) is a disease resulting from immunologically induced inflammation in response to inhalation of a wide variety of airborne allergens. The condition develops mainly in non atopic individuals sensitized to organic dust due to repeated exposures. It is a relatively rare disease constituting upto 2% of interstitial lung diseases. Knowledge of classical High Resolution Computed Tomography (HRCT) of lung findings aid in early diagnosis. We report a case of subacute hypersensitivity pneumonitis in a housewife who despite being symptomatic remained undiagnosed for two years. She showed a good response to therapy, but soon relapsed. Visit to her home revealed that she lived in a damp house full of moldy walls. PMID- 26894118 TI - Isolated CNS Blast Crises in Chronic Myeloid Leukaemia Presenting as Hypertrophic Pachymeningitis and Bilateral Optic Neuritis: A Case Report. AB - Extramedullary blast crises of Chronic Myeloid Leukaemia (CML) involving CNS is rare and usually accompanies systemic relapse. Isolated CNS blast relapse is an extremely uncommon event. A 35-year-old male was diagnosed with chronic phase (CP) CML two years back at our hospital and was started on imatinib 400 mg daily. Patient achieved haematological and cytogenetic remission at three and 12 months respectively but was non-compliant with medications thereafter. He presented to our emergency with headache and bilateral visual loss. CNS examination revealed neck rigidity and fundoscopy revealed disc edema with retinal vein dilatation and haemorrhages. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis and a positive cytospin for myeloid blasts. MRI brain suggested pachymeningeal enhancement involving falx cerebri and tentorium along with bilateral optic nerve thickening. Patient maintained cytogenetic remission at current presentation. A diagnosis of isolated CNS blast crises with pachymeningitis and bilateral optic nerve involvement was made and two doses of intrathecal chemotherapy were administered. However, patient died due to a rapidly downhill course. A previously unreported finding of pachymeningitis with bilateral optic neuritis has been highlighted in this case, along with a brief review of this rare condition. PMID- 26894119 TI - Urinary Tuberculosis with Renal Failure: Challenges in Management. AB - INTRODUCTION: India is the country with the highest burden of TB, an estimated incidence figure of 2.1 million cases of TB for India out of a global incidence of 9 million according to World Health Organization (WHO) statistics for 2013. Renal impairment in these patients is slow and due to continuous infection causing destruction of renal mass. Reconstruction of urinary tract which is frequently required for patients with Urinary TB poses significant challenges. This paper analyses these challenges. AIM: To analyse challenges in reconstruction of urinary tract in patients with urinary tuberculosis and renal failure. MATERIALS AND METHODS: Thirty-one patients with renal tuber-culosis were seen from August 2011 to August 2013. We faced major problem in outcomes of surgery in patients with multifocal disease. RESULTS: Out of 31 patients 18 patients were males and 13 were females. Total 11 patients had serum creatinine more than 2mg/dl (1.5 mg/dl being upper normal range of our laboratory) at the time of presentation. These patients had simultaneous kidney, ureter and bladder involvement or with bilateral disease. Four of these patients underwent uretero calicostomy, five patients underwent augmentation cystoplasty with bilateral ureteric reimplantation and two patients underwent ileal conduit as they were having serum creatinine of more than 2.5 mg/dl. All patients who underwent ureterocalicostomy had re stricture and failure of surgery and augmentation cystoplasty had raised creatinine requiring second procedure in the form of percutaneous nephrostomy. Patients with ileal conduit remained stable with overnight bladder drainage at bed time. CONCLUSION: Though renal failure is not considered contrain-dication for augmentation cystoplasty, reconstruction using large segment of bowel predisposes them to metabolic complications and sepsis. Use of short segment of ileal conduit with continued drainage at night in creatinine above 2.5 mg% is reasonable option for augmentation to avoid further metabolic complications. PMID- 26894121 TI - Spinal Intradural Schwannoma with Acute Intratumoural Haemorrhage: Case Report and Review. AB - Schwannomas account for around half of all intradural spinal tumours, with chronic progressive symptoms as the most common presenting features. Intratumoural haemorrhage as a presenting feature of spinal schwannoma is very rare and only 11 cases have been reported till date. Authors here report a previously asymptomatic 40-year-old male who presented with acute onset paraplegia 12 hours after a minor trauma. MR imaging revealed a C7-D3 intradural extramedullary lesion with features of acute blood and showing no enhancement. Emergency laminectomy and complete removal of the mass was performed and histopathology revealed features of schwannoma with haemorrhage. Patient had modest improvement of his neurological deficits at a follow-up of 6 months. Pertinent literature is reviewed in brief. PMID- 26894120 TI - Impact of Coagulation Profile on Outcome of Head Injury. AB - INTRODUCTION: Worldwide, head injury is recognized as a major public health problem. Head injury patients often develop consumptive coagulopathy in the absence of other trauma or haemorrhages. The release of tissue factor from the damaged brain is postulated as the cause of coagulopathy. AIM: To know the impact of coagulation profile derangements and their effect on the outcome of head injury patients. MATERIALS AND METHODS: Fifty patients in the age group of 20-70 years admitted with isolated head injury were taken. Samples of complete haemogram (CBC), prothrombin time (PTI), partial thromboplastin time (PTK), D Dimers and fibrinogen were taken within 24 hour of admission. Coagulopathy was defined as platelet counts < 100,000 cells/mm(2) and PTI >15 seconds or a DIC score more than 4. The outcome in each group was measured according to Glasgow outcome score. Coagulation abnormalities were analysed. RESULTS: In case of severe head injury, p-values in patients who died with regard to DIC score, Prothrombin time and APTT were found to be significant (p< 0.05). For D-Dimers, fibrinogen and platelets counts the p-value was not significant. In case of moderate head injury, p-values in patients who died with regard to DIC score, platelet count, Prothrombin time, D-Dimer and APTT were found to be significant (0.05). For fibrinogen level it was insignificant. The mean DIC score and mean GOS in the severe head injury patients was significant (p<0.001). CONCLUSION: Patients with isolated head injury are at risk of development of coagulation abnormalities, which is associated with poor outcome. Based on our results we also emphasize the importance of early diagnosis of coagulation abnormalities in isolated head injury patients. PMID- 26894122 TI - Squamous Cell Carcinoma of the Renal Pelvis, A Rare Site for a Commonly Known Malignancy. AB - Chronic nephrolithiasis predisposes to squamous metaplasia and subsequently SCC which is a rare malignancy of the upper urinary tract. A 60-year-old woman with a long standing history of renal calculi presented with flank pain and fever. Investigations revealed a mass in the superior pole of a non functioning left kidney while the right kidney was sub optimally functioning, hydronephrotic and there was presence of bilateral staghorn calculi. Patient underwent decompression of right kidney by double j stenting and left radical nephrectomy that revealed well differentiated squamous cell carcinoma of renal pelvis. Most SCC of the renal pelvis present with advanced disease and dismal prognosis while our patient presented with localized disease without lymphatic and distant metastasis. Thus radical nephrectomy can be curative if the disease can be diagnosed at an earlier stage. This emphasizes the need of early treatment of nephrolithiasis to prevent the development of SCC and screening of patients with long standing staghorn calculi. PMID- 26894123 TI - Persistent Mullerian Duct Syndrome with Embryonal Cell Carcinoma along with Ectopic Cross Fused Kidney. AB - Persistent Mullerian Duct Syndrome (PMDS) is a form of internal male pseudohermaphroditism, where there is normal development of male secondary sexual characters, along with the presence of bilateral fallopian tubes and uterus. Majority of these cases go undetected and some cases are accidentally diagnosed while investigating for other problems. Cross fused renal ectopia is a condition where one kidney lies in the opposite side, fused to the other kidney. We present an extremely rare case of a phenotypical male presenting with mass per abdomen and bilateral cryptorchidism, turned out to have uterus with bilateral fallopian tubes, ectopic cross fused right kidney and Embryonal cell carcinoma of left undescended testis. PMID- 26894124 TI - Comparison of the Perioperative Outcomes of a Vessel Sealing Instrument-Assisted Technique with a Conventional Technique in Abdominal Myomectomy. AB - INTRODUCTION: In gynaecologic practice, LigaSure Precise(TM) is generally used in endoscopic and open surgeries, such as hysterectomy, adnexectomy, and cancer surgery. However, there is no case report or main research article where LigaSure Precise(TM) has been used for myomectomy. We want to compare a technique using a vessel sealing instrument with a conventional technique in abdominal myomectomy. MATERIALS AND METHODS: Fifty-five women who underwent abdominal myomectomy were divided two groups: (1) a vessel sealing instrument-assisted technique (24 patients); and (2) a conventional technique (31 patients) between January 2011 and December 2014 at the Department of Gynaecology and Obstetrics, Gulhane Military Medical Academy, Ankara, Turkey. The data for the operation times, the occurrence of perioperative complications, the hospitalization times, and changes in haemaglobin and haematocrit levels for the two techniques were collected and compared. RESULTS: The mean operation time was 48 minutes for the vessel sealing instrument-assisted technique and 54 minutes for the conventional technique. No statistically significant differences were determined for haemoglobin and haematocrit changes, hospital stay and perioperative complications. CONCLUSION: We did not find any difference in the occurrence of complications, changes in haemoglobin or haematocrit levels, or hospital stay. The vessel sealing instrument-assisted technique is feasible and effective in reducing operation times. PMID- 26894125 TI - Trends of Various Techniques of Tubectomy: A Five Year Study in a Tertiary Institute. AB - INTRODUCTION: Female sterilization is one of the best and effective methods of contraception for women who have completed their family. Tubectomy during caesarean operation and minilaparotomy are popular methods in developing countries whereas laparoscopic sterilization and hysteroscopic tubal occlusion are the preferred methods in developed countries. AIM: To know the trends, incidence and immediate complications of methods of female sterilizations performed at our institute. MATERIALS AND METHODS: This is a retrospective analytical study conducted at our tertiary care centre from January 2010 to December 2014 in Karnataka Institute of Medical Sciences, Hubli, Karnataka. The case files of all the patients who underwent sterilization were taken from the medical records section and reviewed in detail. The cases were grouped as caesarean tubectomy, minilaparotomy and laparoscopic sterilization, based on the abdominal entry. For minilaparotomy and during caesarean tubectomy, modified pomeroy's technique was used. For laparoscopic sterilization, falope rings were used. Data was analysed by Karl Pearson's correlation co-efficient method and Chi Square test. The p-value < 0.05 was considered significant. RESULTS: Out of 5442 cases of female sterilization, 2872 underwent caesarean tubectomy, remaining half underwent minilaparotomy (1306) and laparoscopic sterilization (1264). Sterilizations were significantly more during puerperal period (caesarean tubectomy + post abortal + postpartum) compared to interval period. There was an increasing trend in caesarean tubectomy and laparoscopic sterilization. There were 11 procedure related complications in the laparoscopic sterilization, one in caesarean tubectomy and none in minilaparotomy. Two deaths were reported in minilaparotomy, one in laparoscopic sterilization and four in the caesarean tubectomy, which were due to septicaemia. CONCLUSION: An increasing trend in caesarean tubectomy and laparoscopic sterilization is seen in this study. Female sterilization should be individualized based on the timing, place and surgeons experience. Sepsis is a major cause of death and asepsis could be compromised when female sterilization is done in large numbers in camps. Hence target related approach towards female sterilization should be avoided. Laparoscopic sterilization has more procedure related complications, which can be better handled in tertiary care centres. PMID- 26894126 TI - Open-label, Prospective, Investigator Initiated Study to Assess the Clinical Role of Oral Natural or Synthetic Progesterone During Stimulated IUI Cycles for Unexplained Infertility. AB - BACKGROUND: Unexplained infertility remains as one of the important subtype of infertility that follows expectant management with Intrauterine Insemination (IUI) in most cases. AIM: To evaluate the clinical role of progesterone supplement as luteal phase support for women with unexplained infertility following stimulation protocol with Clomiphene Citrate (CC)/Human Menopausal Gonadotropin (HMG). MATERIALS AND METHODS: An investigator initiated study to survey the success rate for first cycle of IUI following stimulation protocol with CC/HMG & luteal phase support with oral natural or synthetic progesterone was conducted. 120 patient records between observation period of Jan to May '14 were retrieved especially for subjects undergoing IUI procedure for Unexplained infertility. Patients with baseline Serum (Sr). progesterone records who received Oral Natural Micronized Progesterone Sustained Release (Oral NMP SR) (N=45) or Dydrogesterone (n=33) following CC/HMG induction protocol and human Chorionic Gonadotropin(HCG) Inj., were further analysed following Luteal Phase Support(LPS) with oral natural or synthetic progesterone. RESULTS: Baseline demographics showed 78 patients with mean age, weight and cycle duration of 29.5 yrs, 57.3 kg & 28.6 days respectively. Progesterone was supplemented as Oral NMP SR 200/300 mg OD or Dydrogesterone 10 mg bid in 22, 23 and 33 patients respectively. In all cases ovulation was triggered with HCG inj., followed by IUI within the next 48 hours while baseline sr. progesterone levels were being assessed. Medicines and Healthcare Products Regulatory Agency (MHRA) UK recommended therapeutic compliance to suggest sr. progesterone levels of >=14ng/ml were recorded as Mid luteal levels in all of these patients. This therapeutic compliance was noted in 82.2% & 78.8% of the patients treated with oral NMP SR or Dydrogesterone respectively. Pregnancy was observed amongst 5 and 10 patients treated with oral NMP SR and Dydrogesterone respectively at the end of 'First' IUI cycle. Both the groups were well tolerated with drowsiness documented in three cases for Oral NMP SR. CONCLUSION: Clinical supplementation with ONMPSR suggests therapeutic compliance and alternative strategy to conventional formulations while offering dosing convenience with minimal side effects. PMID- 26894127 TI - A Comparison Between Non-Descent Vaginal Hysterectomy and Total Abdominal Hysterectomy. AB - INTRODUCTION: Hysterectomy is one of the most common gyneacological surgeries performed worldwide. The vaginal technique has been introduced and performed centuries back, but has been less successful due to lack of experience and enthusiasm among Gynaecologists, due to a misconception that the abdominal route is safer and easier. AIM: To evaluate the most efficient route of hysterectomy in women with mobile nonprolapsed uteri of 12 weeks or lesser by comparing the intra and postoperative complications of vaginal and abdominal hysterectomies. MATERIALS AND METHODS: A prospective, randomized controlled trial was performed wherein, 300 consecutive patients requiring hysterectomy for benign diseases were analysed over a period of 2 years (December 2012-November 2014). Group A (n = 150) underwent vaginal hysterectomy (non descent vaginal hysterectomy, NDVH) which was compared with group B (n = 150) who had abdominal hysterectomy. The primary outcome measures were operative time, intraoperative blood loss, postoperative analgesia, hospital stay, postoperative mobility, blood transfusion, wound infection, febrile morbidity and postoperative systemic infections. Secondary outcome measures were conversion of vaginal to abdominal route and re-laparotomy. RESULTS: Baseline characteristics were similar between the two groups. There were no intraoperative complications in either group. Regarding operation duration, intraoperative blood loss, postoperative pain, postoperative blood transfusion, mobilization in post operative ward, postoperative wound infection, febrile morbidity, duration of hospital stay, p value was significant in vaginal hysterectomy compared to abdominal hysterectomy. Regarding postoperative systemic infections, p-value was not significant. None of the cases in the vaginal group were converted to abdominal route and none of the cases in the whole study group underwent re-laparotomy. CONCLUSION: The present study concludes that patients requiring hysterectomy for benign non prolapse cases may be offered the option of vaginal hysterectomy which has quicker recovery, shorter hospitalization, lesser operative and postoperative morbidity compared to abdominal route. PMID- 26894128 TI - Awareness and Determinants of Contraceptive use among Nursing Mothers in Bellary, Karnataka. AB - INTRODUCTION: The nursing mothers, who have already delivered a child in recent period, may prefer to avoid or delay future pregnancy, or may not even have given a thought about it. Among those who prefer to delay next pregnancy, many are unaware of family planning practices. This is mainly influenced by the prevailing sociodemographic factors in their families. AIM: To study the prevailing Knowledge, Attitude and Practice of contraception and the influence of sociodemographic factors on family planning practices among the healthy nursing mothers. MATERIALS AND METHODS: A cross-sectional study was conducted among 2500 healthy breast feeding mothers who delivered at Medical College Hospital (MCH), Vijayanagara Institute of Medical Sciences(VIMS), Bellary during Dec 2011 to Nov 2013. They were interviewed using a pre structured questionnaire in the post natal wards on 2(nd) to 7(th) postpartum day. Later these mothers were educated and counseled regarding various suitable contraceptive methods. The data collected were analysed using percentage and chi- square test. RESULTS: The proportion of willingness for contraception is more among women in the age group 19-29 years, among literate husband and wife, among women belonging to nuclear families and with higher socioeconomic status. Muslim women were least receptive to contraceptive advice. Regarding awareness of contraceptive methods only 46% had knowledge regarding family planning methods. A total of 43% mothers opted to limit family size. Among 16% of mothers who did not want to limit family size, 70% had no male child. In most of the families, final decision regarding family planning method was taken by husband alone or by elders. The most important reason for lack of family planning practices was lack of awareness (57.2%). CONCLUSION: Many of the nursing mothers are not aware of contraceptive practices. But these women are very receptive to contraceptive advice. Also, the decision of family planning depends not only on the couples but even on elders of the family. Hence, a combined family approach to educate and counsel the entire family including elders is needed. The major determinant is education of the entire family regarding family planning practices. PMID- 26894129 TI - Prenatal Diagnosis of Umbilical Artery Aneurysm with Good Fetal Outcome and Review of Literature. AB - Umbilical artery aneurysm is a rare condition. Till date, 14 cases are reported and only 4 had good fetal outcome. Umbilical artery aneurysm is associated with high risk of fetal aneuploidy and fetal demise. Though umbilical cord anomalies are rare, they are associated with significant fetal morbidity and mortality. We report a case of umbilical artery aneurysm which was detected at 33 weeks of gestation on ultrasonography as an anechoic cyst close to cord insertion with turbulent blood flow in it. The patient was hospitalized and with intensive fetal surveillance and early delivery, a live born fetus was achieved. Baby's karyotype was normal. Pathologic examination confirmed umbilical artery aneurysm close to cord insertion. PMID- 26894130 TI - Amniotic Band Syndrome - A Dreaded Condition. AB - Amniotic band syndrome is a unique condition in which amnion a normal structure causes complications. A case of second gravid, obese who is a known diabetic came to OPD at 13 weeks pregnancy for regular antenatal check up. A routine ultrasonogram was advised in which multiple anomalies were noted and the diagnosis of amniotic band syndrome was made. The parents were counseled for medical termination of pregnancy and after obtaining the consent termination were performed and the parents were asked to postpone the next pregnancy for minimum 6 months. This anomaly as seen in this patient could be due to risk factors like diabetes and obesity. PMID- 26894131 TI - A Rare Cause of Placental Abruption: Uterine Torsion. AB - Uterine torsion is defined as a rotation on its long axis and it is a dangerous, unexpected obstetric emergency. We report a case of uterine torsion at 32 weeks of gestation in a singleton pregnancy. A 37-year-old woman with multiple prior cesarean deliveries referred to emergency unit of our hospital at 32 weeks of gestation with severe abdominal pain and mild vaginal bleeding. Ultrasonography showed a single fetus in vertex position, with a normal amniotic fluid. Fetal biometer was appropriate for 32 weeks of gestation. Placental location was anterior with a subchorionic hypoechogenic small area which was suspected to be a sign of placental abruption. An emergency cesarean section was performed under general anesthesia. The 180 degrees uterine torsion was diagnosed and it was not possible to perform detorsion of the gravid uterus by exteriorization by pfannenstiel incision. Posterior hysterotomy was performed and a male baby of 1830 grams weight was delivered. The newborn was transported to Neonatal Intensive Care Unit (NICU) of another hospital and discharged within two weeks. Patient recovered well and was discharged on second postoperation day. Uterine torsion is a very rare and life threatening situation. In unexpected cases posterior low transuerse hysterotomy is generally performed and it is suggested as a safe choice when detorsion was not accomplished. It is not easy to keep in mind the possibility of uterine torsion in cases of abdominal pain during pregnancy. Because it generally causes abruption, management of abruption is vitally important to prevent fetal mortality. PMID- 26894132 TI - A Prospective Study on Functional Outcome of Internal Fixation of Tibial Pilon Fractures with Locking Plate using Minimally Invasive Plate Osteosynthesis Technique. AB - INTRODUCTION: Managing pilon fractures is still a great challenge for surgeons in terms of reduction and fixation. The soft tissue anatomy and the bony configuration, results in angular and rotational instability and other bony and soft tissue complications. AIM: To evaluate the results of minimally invasive plate osteosynthesis using locking plates in management of fractures of tibial pilon in terms of radiological fracture union, restoration of ankle function and complications. MATERIALS AND METHODS: A total of 18 patients with Ruedi Allgower class I, II & III fresh pilon fractures were taken into this study. All the patients underwent ankle spanning external fixator application on the day of presentation as a first stage. Wound debridement was done in patients with open fractures. Associated distal fibula fractures were fixed in the first stage. The second stage comprised of a definitive plate fixation using the minimally invasive plate osteosynthesis technique. This employed minimal periosteal and soft tissue dissection through a medial approach to the ankle. Postoperatively, all patients were reviewed at week six and 12 when partial weight bearing and full weight bearing mobilization was started respectively. The final review was done at 24 weeks when the final assessment of function was done as per the Mazur's scoring criteria. Analyses were done using frequency and proportions. Chi square tests were used to assess the test of association. RESULTS: Three patients had excellent inference, nine patients had good inference, five patients had fair and one patient had poor inference as per the Mazur's scoring criteria. Two patients had scar dehiscence as a complication and one patient had a fixed equines deformity of the ankle who was under RuediAllgower class III. CONCLUSION: Minimally invasive plate osteosynthesis is an excellent method of treating pilon fractures with very good functional results and minimal complication rate. PMID- 26894133 TI - Osteosynthesis in Distal Radius Fractures with Conventional Bridging External Fixator; Tips and Tricks for Getting Them Right. AB - BACKGROUND: Distal radius fractures are the commonest fractures occurring in the upper extremity, accounting for 15-20% of patients treated in emergency department. Although distal radial fractures were described 200 years ago, they still remain as unsolved fractures with no clear guidelines. It is often reported that anatomical reduction has a bearing on the functional outcome. AIM: To study the management of distal end radius fracture by utilizing the principle of ligamentotaxis where in the reduction obtained by closed means is maintained by external fixator till solid bony union occurs. MATERIALS AND METHODS: A total of 26 cases were selected for study by scrutiny of the inclusion and exclusion criteria. Most of our cases were treated with external fixator within 8 hrs of injury. Small A.O external fixator (bridging ex-fix) with 2 pins each in radius and 2(nd) metacarpal percutaneously was used for all the cases. Selective k wire fixation was done in cases of instability. Fixator was removed after 6 weeks. Guided physiotherapy was ensured in all the cases. Patients were followed up for an average of 9 months. RESULTS: Modified Gartland and Werley scoring system was used to evaluate the overall functional results. Excellent to good results were achieved in 88.45% of our cases while fair result was in 11.54 %. One case had pin loosening and two other cases had malunion. CONCLUSION: External fixator used for ligamentotaxis is an effective method of treating unstable extraarticular and complex intraarticular fractures of distal radius. Improved anatomical restoration with early rehabilitation has produced favourable functional outcome in our series. The complications like pin tract infection is rare due to the availability of superior antibiotics and sterile surgical technique. complications like wrist and finger stiffness has improved with physiotherapy. PMID- 26894134 TI - Unstable Intertrochanteric Fracture Fixation - Is Proximal Femoral Locked Compression Plate Better Than Dynamic Hip Screw. AB - BACKGROUND: Intertrochanteric fractures are one of the most common fractures encountered in our practice. Most of them need operative intervention and union is achieved. As per the literature dynamic hip screw (DHS) is the gold standard for the treatment of these fractures, however problem arises with maintenance of neck shaft angle and proper reduction in unstable intertrochanteric fractures. The situation gets more complex when "cut out" of femoral head screw occurs either alone or in combination with varus collapse when they are treated with DHS. Here we are giving results of unstable intertrochanteric fractures treated with Proximal Femoral Locked Compression Plate (PFLCP) as compared with similar patients treated with Dynamic Hip Screw (DHS). MATERIALS AND METHODS: The study included a total of 27 patients (17 males, 10 females) with unstable intertrochanteric fractures who were subjected to PFLCP treatment from March 2011 to November 2012 in one group. Another was a similar group of 35 patients treated with DHS from March 2008 to February 2010. Results of group 1 were compared with group 2. Detailed clinical conditions of all patients, duration of surgery, blood loss, length of incision and duration of image intensifier use were recorded. Patients were revisited at 6 weeks, 3 months, 6 months and 1 year after operation. Results were evaluated clinically by Harris hip Score and radiologically for fracture union. Progress of union and complications (limb shortening, varus collapse, cut out of femoral head screw and medialization of distal fragment) were recorded. RESULTS: Among 27 patients treated with PFLCP, one patient expired 6 week postoperatively and one patient lost to follow up, so 25 patients were evaluated for final outcome of which 23 (92%) showed union at follow up of 12 months. One patient developed bending of proximal screws and three developed varus collapse. Among the group treated with DHS, eight patients developed varus collapse, seven developed medialization and three had femoral head screw cut out. According to Harris hip Score 88% cases had good to excellent result in PFLCP group whereas only 60% cases in the DHS group had good to excellent result. CONCLUSION: Treatment of unstable intertrochanteric fractures with proximal femoral locked plate (PFLCP) can give good healing, with a limited occurrence of complication. PMID- 26894135 TI - Primary Extrapulmonary Multidrug-Resistant Tuberculosis of the Sternum without HIV Infection. AB - Skeletal tuberculosis (TB) accounts for about 9% of all TB cases. Tuberculosis of the sternum is not a common presentation. The case of primary multidrug-resistant (MDR) TB of the sternum is even rare. So far no such case has been reported in the medical literature. Herein, we present the very first case of primary extrapulmonary MDR TB of the sternum in a 21-year-old immunocompetent Indian female who presented with chest pain and an increased swelling over the anterior chest with an intermittently discharging sinus. She was diagnosed with multidrug resistant tuberculosis of the sternum without the active pulmonary disease. Conservative management with oral multidrug antitubercular therapy (ATT) completely cured the patient. PMID- 26894136 TI - Mystery of Sciatica Resolved - A Rare Case Report. AB - Schwannomas are common, benign, slow growing tumours of peripheral nerve sheath arising from the schwann cells of the neuroectoderm. They do not transverse the nerve but remain within the sheath on top of the nerve. They rarely present in the sciatic nerve. Sciatic schwannomas may mimic symptoms of herniated disc, usually with radiation of pain to buttocks and thigh region with inability to walk for long distances and sometimes may present with claudication. In the absence of low back pain and with a normal Lumbo-Sacral MRI study, causes intrinsic to sciatic nerve needs to be thought off, which often delays the diagnosis. Rarity in our case-patient presented with tingling sensation and inability to squat on hard surface for more than 10 minutes with a normal x-ray and MRI study of lumbosacral spine. PMID- 26894137 TI - Intraosseous Epidermoid Inclusion Cyst of Distal Phalanx: A Rare Entity. PMID- 26894138 TI - Study of Weight Patterns in Exclusively Breast Fed Neonates- Does the Route of Delivery have an Impact? AB - INTRODUCTION: Physiological weight loss is seen in all breast fed neonates. The route of delivery may have an effect on the neonatal weight loss/gain in these exclusively breast fed babies. Additional assistance and support for exclusive breast feeding is needed by mothers who undergo cesarean section. AIM: To study and compare the weight patterns in full term exclusively breast fed neonates born by normal vaginal route versus cesarean section in the first month of life. MATERIALS AND METHODS: It is a prospective observational study. Healthy, full term neonates born by normal vaginal route or cesarean section in a rural tertiary hospital with uneventful perinatal periods were included. Exclusive breast feeding was given to all neonates with supervision and encouragement to the mothers. Primary outcome measure- Weight loss of the neonates at 24 hours and 72 hours of life. RESULTS: Neonates delivered by cesarean section showed a higher weight loss (% of birth weight) at 24 hours {mean(sd)} than those delivered vaginally {3.2 (1.9) vs 2.2 (1.2); p-value=0.0016}. At 72 hours, the cesarean neonates had higher weight loss than vaginally delivered neonates {5.9 (3.1) vs 4.7 (2.5); p-value=0.0314}. At 28 days of life, the neonates born by cesarean section showed lower weight gain than those delivered by vaginal route {10.9 (2.1) vs 11.9 (2.3); p-value=0.0244}. CONCLUSION: The route of delivery has a significant impact on the physiological weight loss seen in exclusively breast fed neonates. Babies delivered by cesarean section showed significantly higher weight loss in the first week of life, and lower weight gain at the end of first month than babies born by vaginal route. PMID- 26894139 TI - Parameatal Urethral Cyst in a Newborn-A Case Report and Review of the Literature. AB - Parameatal urethral cysts are rare congenital lesions of the penis that are usually <1cm in diameter in the paediatric population and do not create any urinary difficulties. Their natural course is either to resolve or to be surgically excised without any postoperative complications. We report a case of a newborn with a parameatal urethral cyst that produced voiding difficulties and was treated by surgical excision. PMID- 26894140 TI - Celiac Axis, Common Hepatic and Hepatic Artery Variants as Evidenced on MDCT Angiography in South Indian Population. AB - INTRODUCTION: With the increase in the hepatobiliary, pancreatic surgeries and liver transplantation, being aware of the anatomic variations of the celiac axis and the hepatic arteries is of paramount importance. AIM: To illustrate the normal anatomy and variants of the celiac axis and the hepatic arteries with multidetector computed tomographic (MDCT) angiography in South Indian population and determine the potential variations in the celiac axis anatomy and the hepatic arteries, thus assisting the hepatobiliary surgeon and the interventional radiologist in avoiding iatrogenic injury to the arteries. MATERIALS AND METHODS: Two hundred patients undergoing abdominal CT angiography from July 2014 till July 2015 were retrospectively studied for hepatic arterial and celiac axis anatomical variation. The anatomic variations in our study were correlated with other studies. RESULTS: The celiac axis (CA) and the hepatic artery (HA) variations were analysed as per criteria laid by Song et al., and Michel. Out of 15 possible CA variations, 5 types of celiac artery variations were seen in 14 patients. A normal CA was seen in 179(89.5%) patients of the 200 patients. In the remaining 7 patients, the CA anatomy was classified as ambiguous since there was separate origin of the right and left hepatic arteries from the CA with absent common hepatic artery (CHA). The CHA originated normally from the celiac axis in 94% of the cases. Variation of CHA origin was seen in 5 patients. Normal HA anatomy was seen in 114 (57%) patients. Variation in HA anatomy was seen in 86 (43%) patients. Origin of the right hepatic artery (RHA) from the hepatic artery proper was seen in 182 (91%) patients and replaced origin of RHA from the superior mesenteric artery (SMA) was seen in 18 (9%) of the cases. Accessory RHA was seen in 7(3.5%) patients. The left hepatic artery (LHA) originated from the hepatic artery proper in 186 (93%) patients and replaced origin of LHA from the left gastric artery (LGA) was found in 14 (7%) patients. Accessory left hepatic artery was found in 22(11%) cases. Double hepatic artery seen in 7(3.5%) patients. CHA replaced to LGA was seen in 1 patient (0.5%). CHA trifurcation was seen in 11 (5.5%) patients. CHA was replaced to SMA in 4 (2%) cases. CONCLUSION: Our study identified the normal anatomy and variations in celiac axis and hepatic arterial anatomy in South Indian population, which correlated well with studies in other populations. PMID- 26894141 TI - Colour Doppler Evaluation of Extracranial Carotid Arteries: A Clinical and Radiological Correlation. AB - INTRODUCTION: Atherosclerosis (i.e. hardening and thickening of arteries) causes vascular remodeling, obstruction of lumen, abnormalities of blood flow and reduced oxygenation of target tissues. Manifestation of atherosclerosis in the form of either Myocardial Infarction or Stroke is the major cause of morbidity and mortality. This study evaluated extracranial carotid arteries of patients (>60 years) who presented with risk factors of atherosclerosis and determined the association of risk factors with carotid abnormalities. AIM: To evaluate the prevalence of atherosclerosis, haemodynamic and morphological changes that take place in extra cranial portion of carotid arteries in patients with risk factors of atherosclerosis (Diabetes Mellitus, Hypertension, Smoking, Stroke, Coronary Artery Disease, Hypercholesterolaemia) and determine the association of risk factors with carotid abnormalities. MATERIALS AND METHODS: The prospective cross sectional analytical study included the examination of Extracranial carotid arteries of 1043 patients over a period of 2 years (2013-2015) using duplex ultrasound. Assessment of CCA-IMT, ICA-IMT and percent stenosis was done using a linear probe of 8-12 MHz. STATISTICAL ANALYSIS: Correlation between risk factors of atherosclerosis, wall thickness of common carotid (CCA-IMT), internal carotid arteries (ICA-IMT) and stenosis was studied using statistical tools like multiple logistic regression analysis and analysis of variance (p<0.05) using SPSS 17.0. RESULTS: Maximum percent stenosis increased with increase in age. Prevalence of severe stenosis (>70%) was low while the prevalence of mild stenosis (<50%) was quite high. In all age groups, stenosis was more prevalent and more severe in men as compared to women. Hypertension showed the strongest positive correlation with all three measures of interest CCA-IMT, ICA-IMT and maximum percent stenosis. Stroke history showed strong positive correlation with CCA-IMT and stenosis. Smoking, Diabetes Mellitus, Hypercholesterolaemia, Heart disease showed strong association with all three measures as well. Atherosclerotic plaques were mostly found at the site of carotid bifurcation. CONCLUSION: CCA-IMT was strongly associated with hypertension, smoking and diabetes mellitus. ICA-IMT was strongly associated with hypertension and history of heart disease. Percent stenosis was strongly associated with smoking and history of heart disease. PMID- 26894142 TI - Age-Related Normogram for Ovarian Antral Follicle Count in Women with Polycystic Ovary Syndrome and Comparison with Age Matched Controls Using Magnetic Resonance Imaging. AB - INTRODUCTION: Antral Follicle count (AFC) is a reliable marker for ovarian reserve. Previous studies have used transvaginal ultrasound for estimation of AFC, however we used magnetic resonance imaging (MRI) for estimation of AFC and for creating an age-related normogram in patients with polycystic ovary syndrome (PCOS) and compared it with normal patients. AIM: The aim of this study is to create an age related normogram for AFC in women with PCOS and to compare that with women without polycystic ovarian syndrome using MRI. MATERIALS AND METHODS: A total of 1500 women were examined, out of which 400 fitted the criteria for PCOS. They all underwent MRI study and similar age matched women without PCOS also underwent MRI examination. Normogram for AFC were obtained using LMS software and a percentile chart was obtained. RESULTS: Normogram for AFC in PCOS women showed decline in number of AFC as the age progresses and the decline was linear. The normogram for AFC was compared with equal number of patients without PCOS and they also showed decline in AFC as the age progresses, however the decline was exponential and faster. CONCLUSION: Age related normogram for AFC is widely used and considered as best clinical predictor for ovarian response in assisted reproductive technology. Knowledge of ovarian reserve is important in PCOS and non-PCOS females as PCOS patients are at risk for ovarian hyperstimulation syndrome during gonadotrophin theraphy. MRI is an equally effective and in some times better alternative to transvaginal ultrasound as it has got its own advantages. PMID- 26894143 TI - Multiple Enchondromatosis: Olliers Disease- A Case Report. AB - Olliers disease is a rare disease characterized by widespread enchondromas with a unilateral predominance, in early childhood. The diagnosis is based on clinical and conventional radiological evaluations. The prognosis for olliers disease is difficult to assess. Enchondromas in olliers disease present a risk of malignant transformation into chondrosarcomas. Due to its rarity literature focusing on olliers disease is limited. This case report discusses the case of a 12-year-old female who presented with difficulty in walking, leg pain and multiple painless swellings in hands and legs for a period of 2 years. PMID- 26894144 TI - A Case of Cervical Spine Tuberculosis in an Infant. AB - Tuberculosis of cervical spine is an extremely rare entity in infants with only few case reports available in the literature. The diagnosis is often delayed due to less dramatic effects of paraplegia or quadriplegia in an infant as compared to older paediatric population. Along with clinical and laboratory investigations, imaging plays a crucial role in defining the extent of involvement, evaluation of complications, providing suitable differential diagnosis and monitoring response to treatment. Tuberculosis typically involves the discovertebral complex while involvement of isolated vertebral body or multiple vertebrae without involving the intervertebral discs is much less common. We present such an unusual case of cervical spine tuberculosis in an infant involving a single vertebral body without adjacent intervertebral disc involvement complicated with tuberculous meningitis (TBM) and communicating hydrocephalus. The early medical intervention in this case resulted in early diagnosis, active treatment and resultant near normal recovery. PMID- 26894145 TI - A Case Report of Metronidazole Induced Neurotoxicity in Liver Abscess Patient and the Usefulness of MRI for its Diagnosis. AB - Metronidazole is a very widely used drug for the treatment of multiple ailments caused by anaerobic bacteria as well as some protozoan parasites. Though its usual side effects are not very serious, yet sometimes it may cause profound adverse effects like neurotoxicity. We present here a case of liver abscess. The patient was treated for a long time with metronidazole and developed sudden onset neurotoxicity which was diagnosed by MRI. The present case also highlights the need of vigilant monitoring of patients on metronidazole for symptoms of neurotoxicity and the usefulness of MRI for diagnosis of the same. PMID- 26894146 TI - A Case of Metastatic Esophageal Carcinoma in a Pregnant Woman with Radiologic Findings. AB - The incidence of all malignant tumours during pregnancy is extremely rare and esophageal carcinoma ranges from 0.07 to 0.1% of all malignant neoplasms. The physiological changes during pregnancy frequently mask the complaints and symptoms related to the disease. The physical and physiological clinical conditions limit the diagnostic approaches. Therefore, the stage of cancer at the time of diagnosis is usually advanced. The management with cancer surgery and chemotherapy regimens must be modified in pregnant women in order to minimize fetal and maternal risks. Here, we report a very rare case of metastatic esophagus cancer in a 39-year-old woman with 28 weeks of pregnancy and aim to show the ultrasound (USG) and magnetic resonance imaging (MRI) findings with treatment and follow up management. PMID- 26894147 TI - Renal Papillary Necrosis: Role of Radiology. AB - Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID- 26894148 TI - Persistent Primitive Hypoglossal Artery (PPHA) - A Rare Anomaly with Literature Review. AB - Persistent primitive hypoglossal artery (PPHA) is a rare embryonic carotid vertebrobasilar artery anastomosis. Hypoglossal artery arises from the internal carotid artery (ICA) between the C1 and C2 vertebral levels and traverses through the hypoglossal canal to join the vertebro-basilar system. We present a rare case of an anomalous right sided PPHA as a sole supply to posterior circulation of brain with absent/hypoplastic bilateral vertebral arteries in a two year child who had presented with acute left sided haemiplegia. Three dimensional time of flight magnetic resonance angiography identified an anomalous vessel arising from the right internal carotid artery at the level of axis vertebra and joining the vertebra-basilar arterial system after coursing through the right hypoglossal canal. This anomaly when present may predispose the person to aneurysm formation, ischaemia in the posterior circulation and atherosclerotic disease of the intracranial vessels. PMID- 26894149 TI - Multiple Isolated Enteric Duplication Cysts in an Infant - A Diagnostic Dilemma. AB - Completely isolated enteric duplication cysts are a rare variety of enteric duplication cysts having an independent blood supply with no communication with any part of the adjacent bowel segment. We report a case showing two completely isolated enteric duplication cysts originating in the greater omentum and transverse mesocolon in an infant. Multiple isolated enteric duplication cysts involving non-contiguous bowel segments have not been previously reported in the literature. In addition the transverse mesocolon duplication cyst was infected showing septations and loss of double wall sign resulting in difficulty in imaging diagnosis. Both the cysts were excised and confirmed on histopathology. PMID- 26894150 TI - Evaluation of Cardiopulmonary Resuscitation (CPR) for Patient Outcomes and their Predictors. AB - INTRODUCTION: Cardiac arrest continues to be a common cause of in-hospital deaths. Even small improvements in survival can translate into thousands of lives saved every year. AIM: The aim of our prospective observational study was to elicit the outcomes and predictors of in-hospital cardiopulmonary resuscitation among adult patients. SETTINGS AND DESIGN: All in-hospital adult patients (age >14) who suffered cardiac arrest & were attended by a Code Blue Team between 1(st) January 2012 & 30(th) April 2013 were part of the study. MATERIALS AND METHODS: The cardiopulmonary resuscitation (CPR) was assessed in terms of: Response time, Presenting initial rhythm, Time to first defibrillation, Duration of CPR and Outcome (Return of spontaneous circulation (ROSC), Glasgow outcome scale (GOS) at discharge). STATISTICAL ANALYSIS: Age, GOS and mean response time were analysed using t-test and ANOVA. Logistic regression was applied to determine the significance of the various factors in determining mortality. RESULTS: ROSC was achieved in 44% of a total of 127 patients included in our study. Asystole/Pulseless electrical activity (PEA) was the most common presenting rhythm (87.5%). The survival to discharge was seen in 7.1% patients of whom only 3.9% patients had good neurological outcome. Regression and survival analysis depicted achievement of ROSC during CPR, absence of co-morbidities and shorter response time of code blue team as predictors of good outcome. CONCLUSION: We found poor outcome of CPR after in-hospital cardiac arrest. This was mainly attributed to an initial presenting rhythm of Asystole/PEA in most cases and delayed response times. PMID- 26894151 TI - Multimodal versus Conventional Approach for Postoperative Pain Relief in Oral Cancer Patients. AB - INTRODUCTION: Multimodal analgesia includes regional anaesthesia in the form of nerve block may improve recovery along with optimal rehabilitation and early resumption of day-to-day activity following major surgery. Conventional general anaesthesia consists of premedication, induction, intubation and maintenance. AIM: The aim of the study is to compare the multimodal versus conventional approach in oral cancer surgery. MATERIALS AND METHODS: The patients were randomly allocated into three groups, 30 patients in each group using the computer generated random table to one of the following groups: Group A: Fentanyl 1 MUg/kg, Group B: Fentanyl 1 MUg/kg + bupivacaine local infiltration, Group C: Fentanyl 1 MUg/kg + bupivacaine local infiltration + Dexemedetomidine infusion (Loading 0.5 MUg/kg, Maintenance 0.2MUg/kg/hr). RESULTS: No significant (p>0.05) difference was found in mean arterial pressure and heart rate at different time intervals among the groups. The VAS was lower in Group C than Group B and A. The ramsay sedation scale was higher in Group C than Group B and A. The rescue analgesic for 24 hour was lower in Group C than Group B and A. The time of first time analgesia requirement was significantly (p=0.001) higher in Group C than Group B and A. The rescue analgesic was significantly (p=0.001) lower in Group C (39.29+/-19.67) than Group B (68.33+/-18.49) and A (160.83+/-35.16). CONCLUSION: Multimodal analgesia has beneficial haemodynamic effects during oral cancer surgery with reliable postoperative analgesia and sedation and less postoperative complication. Dose of drugs used in our study is not associated with any major adverse effect. PMID- 26894152 TI - Effectiveness of Stellate Ganglion Block Under Fuoroscopy or Ultrasound Guidance in Upper Extremity CRPS. AB - INTRODUCTION: Stellate Ganglion Block (SGB) is an effective technique which may be used to manage upper extremities pain due to Chronic Regional Pain Syndrome (CRPS), in this study we tried to evaluate the effectiveness of this procedure under two different guidance for management of this syndrome. AIM: The purpose of this study was to evaluate the effectiveness of ultrsound guide SGB by comparing it with the furoscopy guided SGB in upper extermities CRPS patients in reducing pain & dysfuction of the affected link. MATERIALS AND METHODS: Fourteen patients with sympathetic CRPS in upper extremities in a randomized method with block randomization divided in two equal groups (with ultrasound or fluoroscopic guidance). First group was blocked under fluoroscopic guidance and second group blocked under ultrasound guidance. After correct positioning of the needle, a mixture of 5 ml bupivacaine 0.25% and 1 mL of triamcinolone was injected. RESULTS: These data represent no meaningful statistical difference between the two groups in terms of the number of pain attacks before the blocks, a borderline correlation between two groups one week and one month after the block and a significant statistical correlation between two groups three month after the block. These data represent no meaningful statistical difference between the patients of any group in terms of the pain intensity (from one week to six months after block), p-value = 0.61. These data represent a meaningful statistical difference among patients of any group and between the two groups in terms of the pain intensity (before the block until six months after block), p-values were 0.001, 0.031 respectively. CONCLUSION: According the above mentioned data, in comparison with fluoroscopic guidance, stellate ganglion block under ultrasound guidance is a safe and effective method with lower complication and better improvement in patient's disability indexes. PMID- 26894153 TI - Comparison of Epidural Bupivacaine, Levobupivacaine and Dexmedetomidine in Patients Undergoing Vascular Surgery. AB - INTRODUCTION: Levobupivacaine is the s-isomer of racemic Bupivacaine. It is less cardio, neurotoxic and equally potent local anaesthetic compared to its racemate. It is known to cause less Depression of myocardial contractility. Dexmeditomidine when used via epidural route has synergistic effect with local anaesthetics. Majority of patients presenting for vascular surgery are elderly and have associated co-morbidities like diabetes, hypertension, and coronary artery disease. We intend to study safety and efficacy of epidural Levoupivacaine and Dexmedetomidine in this group of patients. MATERIALS AND METHODS: Sixty adult patients undergoing lower limb vascular surgery under lumbar epidural anaesthesia were randomly allocated to three groups. All groups were preloaded with 10ml/kg of crystalloid solution. B group was scheduled to receive 15 ml of racemic Bupivacaine, L-group was scheduled to receive 15ml of Levobupivacaine and LD group received 15ml of Levobupivacaine with 0.5 mics/kg Dexmeditomedine. Time to onset of sensory block to T-10, maximum sensory level achieved, Bromage scale, time to two segment regression, time to total regression, sedation level achieved and patients assessment of quality of anaesthesia were assessed. Haemodynamic parameters were monitored throughout study period. Adverse effects were noted and treated appropriately. RESULTS: Baseline parameters were comparable among all the groups. Time to onset of sensory block to T-10 and maximum level of block achieved, was comparable among the groups. Time to two segment regression and time to total regression was significantly prolonged in LD group compared to other two groups. There was significant bradycardia noted in LD group which required treatment. CONCLUSION: Levobupivacaine can be safely used in elderly high risk patients undergoing vascular surgery. Addition of dexmedetomidine prolongs the duration of anaesthesia and postoperative analgesia. PMID- 26894154 TI - In Spinal Anaesthesia for Cesarean Section the Temperature of Bupivacaine Affects the Onset of Shivering but Not the Incidence: A Randomized Control Trial. AB - INTRODUCTION: Postoperative shivering is a frequent event after cesarean section under spinal anaesthesia. Shivering is uncomfortable for the patient and may interfere with monitoring. The exact aetiology of shivering is unknown and therefore has no definite treatment. AIM: The temperature of injectate affects the spread of drug and so its effect. Therefore the aim of this study was to compare the effect of temperature of bupivacaine on post-spinal shivering in cesarean section. MATERIALS AND METHODS: In this prospective, randomized, controlled, double-blind clinical trial 105 ASA-I/II pregnant women scheduled for caesarean section under spinal anaesthesia were selected and randomized into three groups of 35 each. In all pregnant women spinal anaesthesia was achieved with 2.2 ml of 0.5% hyperbaric bupivacaine given either at L3-L4 or L4-L5 interspace. The temperature of bupivacaine was adjusted to 4 degrees C (group T4), 22 degrees C (group T22) and 37 degrees C (group T37). Shivering characteristic, onset and incidence was noted. All three groups were compared using analysis of variance (ANOVA), adverse effects was compared using chi-square test and Kruskal-Wallis H-test. The p-value < 0.05-considered as significant and p-value <0.01-considered highly significant. RESULTS: There were no differences between the groups regarding age, weight, height, amount of fluid used and blood loss. The incidence of shivering was 51.42%, 51.42% and 45.71% in group T4, group T22 and group T37 respectively, this difference in the incidence was statistically not significant (p=0.858). However, the onset of shivering was earliest (9.87+/-1.82 min) in group T4 as compared to 14.27+/-3.02 min and 12.16+/-2.89 min in group T22 and group T37 respectively and this difference in the onset was highly significant (p= 0.0001). CONCLUSION: In spinal anaesthesia for cesarean section, the temperature of bupivacaine does not influence the overall incidence of post spinal shivering; however cold bupivacaine can provoke early onset of shivering. PMID- 26894155 TI - Dexmedetomidine as an Adjuvant to Pre-Emptive Caudal Epidural Ropivacaine for Lumbosacral Spine Surgeries. AB - INTRODUCTION: Pre-emptive caudal epidural is a proven technique for providing analgesia for spinal surgeries. Prolonged pain relief with no motor blockade is desired for early mobilisation. AIM: Present study aimed to evaluate the effect of addition of Inj dexmedetomidine to caudal ropivacaine on the duration of analgesia, haemodynamic profile and the associated side effects. MATERIALS AND METHODS: In this prospective double-blind study a total of 60 patients undergoing lumbosacral spine surgery were randomised to receive 20 cc of pre-emptive caudal epidural injection of either inj ropivacaine 0.2% (Group R, n =30) or a mixture of Inj ropivacaine 0.2% and Inj dexmedetomidine 1 MUg/kg (Group RD, n =30) under general anaesthesia after the patient was positioned prone for surgery. VAS scores, heart rate, blood pressures and time to rescue analgesia were recorded at regular intervals for the first 24 hours. Data analysis was carried out using Statistical Package for Social Science (SPSS, V 10.5 package). RESULTS: Mean VAS scores were significantly lower in the RD group for up to 12 hours following the caudal block. No clinically significant haemodynamic changes were noted in either of the groups. No other side effects were seen in both the groups. CONCLUSION: These results suggest that inj dexmedetomidine is an effective additive to inj ropivacaine for pre-emptive caudal epidural analgesia in lumbosacral spine surgeries. PMID- 26894156 TI - Ventilating Patient with Refractory Hypercarbia: Use of APRV Mode. AB - A 70-year-old patient referred to our critical care unit with the diagnosis of type II respiratory failure with shock. Patient was a known case of COPD for last 20 years. His chest radiology revealed bilateral infiltrates. Patient was managed conservatively in the form of antibiotics, vasopressor and ventilatory support with SIMV/VC mode. After ventilation with SIMV/VC mode for half an hour his blood gases revealed increasing PaCO2 levels. The same result was obtained with PC mode and ASV and his PaCO2 level reached above 170 mmHg. Then APRV mode was tried with modified settings. The results obtained were satisfactory and in next 24 hours PaCO2 decreased to <66mmHg along with an increasing P/F ratio. APRV is the not recommended as primary mode of ventilation in COPD but in resistant cases it can be helpful as it improves alveolar recruitment and pressure support is added to reduce hypercapnia. PMID- 26894157 TI - Bilateral Carpal Spasm Under Spinal Anaesthesia During Abdominal Hysterectomy: A Case Report. AB - Acute hypocalcaemia is a medical emergency that can have catastrophic implications like tetany, seizures, cardiac arrythmias or laryngospasm if left untreated. We are presenting a case of a 30-year-old female patient undergoing total abdominal hysterectomy with bilateral salpingoopherectomy under spinal anaesthesia. She developed unexpected bilateral carpal spasm intraoperatively which was promptly diagnosed and successfully managed with intravenous calcium administration. We conclude that the anaesthetist should be aware of the clinical presentation of acute hypocalcaemia, its causes and emergency management in the perioperative period to prevent any adverse outcomes. PMID- 26894158 TI - The Difficult Paediatric Airway: Two Cases of large Cystic Hygroma. AB - This is a report of a two cases of difficult intubation experienced in paediatric surgical cases. Both the infants, aged one and three-month-old respectively, had very large cystic hygroma of the neck area. Prior hematological and radiological investigations (USG and CT scan of the swelling) and preanaesthesia check up was done and cases were posted for surgical excision. Case I had difficult airway due to pressure of the tumour/cystic hygroma over the airway and posed difficulty for intubation, but was managed well. Case II had respiratory distress during preoperative period. She had been postponed for surgical excision of the cystic hygroma of neck twice due to the difficulties experienced during intubation. Needle aspiration of hygroma fluid helped to reduce the respiratory distress, and the size of the tumour as well, which further helped in the smooth intubation after a week. The postoperative period was uneventful in both the infants. PMID- 26894159 TI - Post-traumatic Stress Disorder (PTSD) in Children of Conflict Region of Kashmir (India): A Review. AB - Post-traumatic stress disorder (PTSD) occurs due to traumatic events. The last two decades have seen various traumatic events in Kashmiri population, which has led to psychological impact on all population, especially children. PTSD is one of the psychiatric disorders occurring after witnessing of traumatic events. A review of literature regarding PTSD in children of Kashmir (India) has been done to assess the prevalence, causes, neurobiology, risk factors and psychiatric co morbidity associated with it. PMID- 26894160 TI - A Retrospective Study of the Pattern of Sexually Transmitted Infections in Males: Viral Infections in Emerging Trend. AB - INTRODUCTION: Sexually transmitted infections (STIs) continue to be a major public health problem with significant burden on the society even after so many health care programmes being organized by the governmental and non-governmental organizations and awareness created among general public about STIs. Male patients are common visitors to STI clinic than females who are generally traced as a contact in our society. AIM: The aim of this study was to give an overview of the pattern of STIs among males at a tertiary care teaching hospital over a period of 5 years. MATERIALS AND METHODS: A retrospective chart review of the data collected from the clinical records of all male patients, who had attended the STI clinic of Chengalpattu Medical College Hospital, Chengalpattu, Tamil Nadu, for various complaints during the 5 year period from 2010 to 2014 was carried out. All male patients with confirmed STIs were included in the study and those patients without any evidence of STIs either clinically or serologically were excluded from the study. RESULTS: Out of the 4454 male cases who had attended the STI clinic, 175 (3.93%) patients had STIs. Genital wart accounted for the maximum number among the STIs with 61 cases (34.86%), followed by genital herpes 56 (32%), urethral discharge 19(10.86%), non-herpetic genital ulcerative diseases 17(9.71%) and serological test for syphilis (RPR) was reactive in 22 (12.57%) patients. HIV was positive in 68 (1.53%) among the total 4454 male patients attended the clinic. CONCLUSION: Viral STIs occur significantly more than the bacterial STIs because of its incurable and recurrent nature. Health programmes should be still more focused on creating awareness about the minor STIs and to remove the stigma so that the patients attend the proper health care facilities in the early stage itself for treatment thereby, complications and further transmission of the STIs can be avoided. PMID- 26894162 TI - Benign Lymphangioendothelioma - A Case Report. AB - Benign lymphangioendothelioma is an uncommon locally infiltrative lymphatic tumour, presenting as a slow-growing, asymptomatic, reddish-violaceous macule or plaque. Histopathologically, it is characterized by thin-walled endothelial-lined spaces that are interspersed between strands of collagen. It must be recognized and differentiated from angiosarcoma, early Kaposi's sarcoma, in view of major differences in treatment and prognosis. A 24-year-old female presented with a raised lesion over the left leg since 2 years which was associated with minimal itching. Biopsy of the lesion showed thin walled vascular channels lined by single layer of bland endothelial cells at the dermo-epidermal junction, few vessels in the dermis. PMID- 26894161 TI - Effect of Topical Application of the Cream Containing Magnesium 2% on Treatment of Diaper Dermatitis and Diaper Rash in Children A Clinical Trial Study. AB - INTRODUCTION: Diaper dermatitis is referred to the inflammation in outer layers of the skin in the perineal area, lower abdomen, and inner thighs. The lesions are maculopapular and usually itchy, which could cause bacterial or candida infection, and predispose the infants to penis or vaginal and urinary infection and lead to discomfort, irritability, and restlessness. The drugs which have been so far administered for this disease (topical steroids) cause special complications for the sensitive skin in this area. Magnesium (Mg) is known for its anti-inflammatory and wound-healing properties. AIM: The aim of the present study was to study the effect of the cream containing Mg 2% on treatment of diaper dermatitis and diaper rash in children. MATERIALS AND METHODS: In this clinical trial study, 64 children aged less than two years old with diaper dermatitis referring Paediatric Ward of Hajar Hospital were randomly assigned to two groups of 32. Group one was treated with the combined cream Mg 2% and Calendula and group two with Calendula cream alone. The duration of recovery was compared between the two groups. RESULTS: The duration of recovery was significantly lower in the intervention group than the control group (p value<0.001), but there was no significant difference in the lesions size and diapers' number between the two groups. CONCLUSION: Based on the finding of this study, Mg is effective on treatment of diaper dermatitis and could be used for treating diaper dermatitis and other types of dermatitis. PMID- 26894163 TI - Inguinal Lymph Nodes in Carcinoma Penis-Observation or Surgery? AB - INTRODUCTION: In Indian sub-continent the presentation of carcinoma penis is variable. Mostly presents with palpable inguinal lymph nodes but not confirm of metastases. AIM: To evaluate whether all clinically positive nodes are metastatic and decide when to address inguinal lymph node. MATERIALS AND METHODS: A retrospective observational study on carcinoma penis from a regional cancer centre of south India over a period from 2001 to 2012. All the clinical, investigational, operative, pathology details and follow-up data were collected from patient records. RESULTS: Two hundred and thirty cases of carcinoma penis have been identified and 112 cases had clinically positive nodes. In 74 cases fine needle cytology was positive for malignancy and they have been addressed with block dissection with surgery of primary lesion. At two years follow up, 70 patients were identified with inguinal lymph node metastasis and block dissection was performed and all was were positive for malignancy on histology. The rate of recurrence is related to the T stage of the primary tumour. CONCLUSION: It can be concluded that elective surgery is appropriate for palpable inguinal lymph nodes and prophylactic nodal dissection in high risk cases of carcinoma penis. PMID- 26894164 TI - Multiple Primary Dedifferentiated Liposarcoma of the Jejunal Mesentery: A Case Report and Review of Literature. AB - Liposarcoma arising primarily from the intestinal mesentery is a rare malignancy. Malignancy is said to be synchronous when there is occurrence of two or more tumours that have not spread from a common site or recurred and show no evidence of metastasis. Multiple synchronous primary liposarcoma of the mesentery is a very unusual clinical finding. Here, we report a rare case of synchronous multiple primary dedifferentiated liposarcoma of jejunal mesentery in a 36-year old female patient. Radiological investigations aided in making a provisional diagnosis of an ovarian malignancy. A staging laparotomy was performed and general surgeon's help was sought due to the presence of three separate jejunal mesenteric masses of sizes 8x6 cms, 6x6 cms and 25x20 cms respectively. Complete excision of mesenteric masses with one feet of involved jejunum was done and a jejuno-jejunal anastomosis made. The histopathology report was indicative of multiple dedifferentiated liposarcoma of jejunal mesentery. Postoperatively patient received Doxorubicin, Dacarbazine and Ifosfamide based adjuvant chemotherapy in view of poorly differentiated tumour. Patient remains tumour free for the last 12 months of follow up. PMID- 26894165 TI - Tensile Bond Strength of Self Adhesive Resin Cement After Various Surface Treatment of Enamel. AB - INTRODUCTION: In self adhesive resin cements adhesion is achieved to dental surface without surface pre-treatment, and requires only single step application. This makes the luting procedure less technique-sensitive and decreases postoperative sensitivity. AIM: The purpose of this study was to evaluate bond strength of self adhesive resin after surface treatment of enamel for bonding base metal alloy. MATERIALS AND METHODS: On the labial surface of 64 central incisor rectangular base metal block of dimension 6 mm length, 5mm width and 1 mm height was cemented with RelyX U200 and Maxcem Elite self adhesive cements with and without surface treatment of enamel. Surface treatment of enamel was application of etchant, one step bonding agent and both. Tensile bond strength of specimen was measured with universal testing machine at a cross head speed of 1mm/min. RESULTS: Least tensile bond strength (MPa) was in control group i.e. 1.33 (0.32) & 1.59 (0.299), Highest bond strength observed when enamel treated with both etchant and bonding agent i.e. 2.72 (0.43) & 2.97 (0.19) for Relyx U200 and Elite cement. When alone etchant and bonding agent were applied alone bond strength is 2.19 (0.18) & 2.24 (0.47) for Relyx U200, and 2.38 (0.27) 2.49 (0.16) for Max-cem elite. Mean bond strength was higher in case of Max-cem Elite as compared to RelyX U200 resin cement, although differences were non-significant (p > 0.05). CONCLUSION: Surface treatment of enamel increases the bond strength of self adhesive resin cement. PMID- 26894166 TI - Computed Tomographic Evaluation of K3 Rotary and Stainless Steel K File Instrumentation in Primary Teeth. AB - INTRODUCTION: The intention of root canal preparation is to reduce infected content and create a root canal shape allowing for a well condensed root filling. Therefore, it is not necessary to remove excessive dentine for successful root canal preparation and concern must be taken not to over instrument as perforations can occur in the thin dentinal walls of primary molars. AIM: This study was done to evaluate the time preparation, the risk of lateral perforation and dentine removal of the stainless steel K file and K3 rotary instrumentation in primary teeth. MATERIALS AND METHODS: Seventy-five primary molars were selected and divided into three groups. Using spiral computed tomography the teeth were scanned before instrumentation. Teeth were prepared using a stainless steel K file for manual technique. All the canals were prepared up to file size 35. In K3 rotary files (.02 taper) instrumentation was done up to 35 size file. In K3 rotary files (.04 taper) the instrumentation was done up to 25 size file and simultaneously the instrumentation time was recorded. The instrumented teeth were once again scanned and the images were compared with the images of the uninstrumented canals. STATISTICAL ANALYSIS: Data was statistically analysed using Kruskal Wallis One-way ANOVA, Mann-Whitney U-Test and Pearson's Chi-square Test. RESULTS: K3 rotary files (.02 taper) removed a significantly less amount of dentine, required less instrumentation time than a stainless steel K file. CONCLUSION: K3 files (.02 taper) generated less dentine removal than the stainless steel K file and K3 files (.04 taper). K3 rotary files (.02 taper) were more effective for root canal instrumentation in primary teeth. PMID- 26894167 TI - Can MMP-9 be a Prognosticator Marker for Oral Squamous Cell Carcinoma? AB - INTRODUCTION: Invasion and metastasis of malignant tumours severely endanger the life of cancer patients. Squamous cell carcinoma is one of the commonly found malignancies in the oral cavity and its survival rate has not improved from past few decades. Since an important risk factor for oral squamous cell carcinoma is the presence of epithelial dysplasia, it is necessary to check the presence of a prognosticator marker in both of them. As matrix metalloproteinase's (MMP's) are involved in degradation of type IV collagen, which are one of the important components of extracellular matrix components which play a relevant role in several steps of tumour progression such as invasion and metastasis. We have studied MMP-9 expression to evaluate its prognostic potential in oral cancers as well as oral epithelial dysplasia along with tissues of normal oral epithelium. MATERIALS AND METHODS: The expression was examined using immunohistochemistry procedure with MMP-9 in 100 samples including cases of epithelium from normal oral mucosa, oral dysplastic lesions and oral squamous cell carcinoma. One set of formalin fixed, paraffin embedded sections of the three categories were stained by haematoxylin and eosin. The sections were then evaluated under microscope. Data was examined for statistical significance using SPSS 13.0 by Mann-Whitney Test and Kruskal-Wallis Test. RESULTS: With MMP-9 gain of expression was noted from Control group to oral squamous cell carcinoma. Cytoplasmic staining was seen with MMP-9. Statistically highly significant differences were seen between oral epithelial dysplasia and oral squamous cell carcinoma and statistically significant differences were found between the control group and the oral squamous cell carcinoma group. CONCLUSION: This study suggested that oral squamous cell carcinoma shows higher MMP-9 expression as compared to oral epithelial dysplasia followed by epithelium from normal oral mucosa. However, no correlation was found among the histological grades of oral squamous cell carcinoma. PMID- 26894168 TI - Comparison of the Root End Sealing Ability of Four Different Retrograde Filling Materials in Teeth with Root Apices Resected at Different Angles - An Invitro Study. AB - INTRODUCTION: Insufficient apical seal is the significant reason for surgical endodontic disappointment. The root-end filling material utilized should avoid egress of potential contaminants into periapical tissue. AIM: The aim of this study was to compare the sealing ability of four root-end filling materials MTA, Portland cement, IRM, RMGIC in teeth with root apices resected at 0 and 45 angle using dye penetration method under fluorescent microscope. MATERIALS AND METHODS: Hundred extracted human maxillary anterior teeth were sectioned horizontally at the cement-enamel junction. After cleaning, shaping and obturation with gutta percha and AH Plus sealer, the tooth samples were randomly divided in two groups (the root apices resected at 0 degrees and 45 degrees to the long axis of the root). The root resections were carried out by removing 2 mm and 1 mm in both the groups. Following which 3 mm deep root-end cavities were prepared at the apices and the root were coated with nail varnish except the tip. The teeth in both the group were randomly divided into four subgroups each (Pro root MTA, Portland cement, IRM and Light cure nano GIC Ketac N-100). All the retrofilled samples were stored in acrydine orange for 24 hours after which they were cleaned and vertically sectioned buccolingually. The sectioned root samples were observed under fluorescent microscope. RESULTS: The root apex sealing ability of Mineral Trioxide Aggregate (MTA) was superior to Portland cement, Intermediate Restorative Material (IRM) and LC GIC. IRM demonstrated the maximum apical leakage value among all the materials. Portland cement and LC GIC showed comparable sealing ability. CONCLUSION: The angulation whether 0 degrees or 45 degrees angle did not affect the sealing ability of all the four materials used, MTA proved to be one of the superior materials for root-end filling. PMID- 26894169 TI - Impact of Aprotinin - A Proteolytic Enzyme on Postsurgical Symptoms in Patients Undergoing Third Molar Surgeries. AB - INTRODUCTION: Dealing with postoperative pain and inflammation remains an arena for never ending research. Different agents have been the subject of many studies to prevent the occurrence of unpleasant postoperative sequel. Extraction of third molars is often associated with significant deterioration in oral health related quality of life (physical, social and psychological) in immediate postoperative period. The complaints of pain, swelling and limitation of mouth opening, which ensue as a result of acute inflammatory response, are frequent consequences of postsurgical procedures involving extraction of impacted 3(rd) molars. AIM: Aprotinin, a naturally occurring protease inhibitor was assessed for its effectiveness in plummeting postsurgical pain and swelling, after surgical removal of impacted 3(rd) molars. MATERIALS AND METHODS: Thirty randomly selected adult patients age ranging from 16-35 years, who required simultaneous surgical removal of bilateral impacted mandibular third molars were recruited. Before the surgical procedure, randomly selected side of the patient was injected with 1 m of 10,000 Kallikrein Inactivator Units (KIU) of aprotinin sub-mucosally around the surgical site and the contra lateral side with 1ml of isotonic saline as a control following which adequate local anaesthesia was obtained. The surgical removal of impacted 3(rd) molars was conducted in a similar manner on both test and control sides on all patients. Postoperatively, the patients were evaluated for pain and swelling for one week i.e., 1(st), 2(nd) and 7(th) day. RESULTS: It was observed that there was marked clinical reduction in postoperative pain and swelling. There were no adverse affects observed after using aprotinin. CONCLUSION: Since, the current pharmacologic agents being used have adverse effects and associated morbidity which still pose a problem, aprotinin a naturally occurring agent could be efficiently used after surgical extraction of 3(rd) molars in management of postsurgical symptoms and improve patient comfort and quality of life. In future, further studies with use of aprotinin in a large number of patients and comparative studies with other drugs are required. PMID- 26894170 TI - The Release of Elements from the Base Metal Alloys in a Protein Containing Biologic Environments and Artificial Saliva - An Invitro Study. AB - INTRODUCTION: It has been reported that protein containing solutions can accelerate the release of elements from the base metal alloys. AIM: This study aims to determine whether the solution in which an alloy is submerged and the exposure time have any effect on the amount of release of elements from the Ni-Cr and Co-Cr alloys. MATERIAL AND METHODS: A total of 126 specimens were made from the Ni-Cr alloy and 42 specimens were made from Co-Cr alloy in the form of 5mm diameter discs, 2mm in thickness. Dissolution experiments were carried out in Bovine Serum Albumin (BSA) and artificial saliva for a period of seven weeks and atomic absorption spectrophotometer was used for elemental analysis. STATISTICAL ANALYSIS: T-test was done to correlate the difference of elemental release from both BSA and artificial saliva. ANOVA test was done to compare the release at different time intervals and to compare the release of elements at different time intervals within a particular solution. TUKEY HSD test was done for comparison between the elements in a particular solution. RESULTS: The results showed that the elemental release was seen in both the solutions with a significant increase of release in BSA. The release of elements from the Ni-Cr alloy showed the predominant release of Cr. CONCLUSION: The protein containing solution showed maximum release of elements from Ni-Cr and Co-Cr alloys. The elements that released from the alloys never reached their threshold for toxic effects. Hence these alloys can be safely used in fabrication of metal restorations without any ill effects. PMID- 26894171 TI - Oral Health Status of Underground Coal Mine Workers of Ramakrishnapur, Adilabad District, Telangana, India - A Cross-Sectional Study. AB - INTRODUCTION: Standard of living and quality of life of people has been improved by the expanding industrial activity, but at the other end it has created many occupational hazards. Coal mining is one of the major age old industries throughout the world and in India. Till date very less literature is available worldwide and in India concerning the oral health status of laborers in this field. AIM: To assess the oral health status of underground coal mine workers, oral hygiene practices, alcohol and tobacco habits. MATERIALS AND METHODS: A cross-sectional descriptive study was conducted among the underground coal mine workers of a coal mine located in Adilabad district, Telangana, according to the criteria described in the World Health Organization (WHO) Oral Health Assessment form (2013). STATISTICAL ANALYSIS: Descriptive statistics were done. RESULTS: A total of 356 workers participated in the study. Ninety percent of the subjects were with tobacco and/or alcohol habits. Dental caries was prevalent in more than half (55.6%) of the study subjects with a mean DMFT of 2.32+/-2.99. About 48.3% study subjects were with untreated dental caries and 20.3% subjects were with missing teeth. DMFT <==6 was seen in 45.5% of subjects and 10.1% have DMFT scores >==7. Periodontal disease was the most prevalent condition seen in the population with 94.4% subjects having unhealthy periodontium in terms of gingival bleeding and/or periodontal pockets. About 186 (52.25%) and 145 (40.73%) of subjects were with 0-3mm and 4-5mm loss of attachment respectively. Fourteen percent of population showed dental traumatic injuries. CONCLUSION: The findings highlighted the high caries prevalence, higher periodontal disease, traumatic injuries which requires immediate intervention. PMID- 26894172 TI - A Clinical Evaluation of Gingival Overgrowth in Children on Antiepileptic Drug Therapy. AB - INTRODUCTION: Gingival overgrowth, a well-known side effect of chronic phenytoin therapy has also been known to be caused by other anti epileptic drugs (AED's). Various factors like plaque, gingival inflammation, and periodontal health have been postulated to effect gingival overgrowth. AIM: To identify the AED having an effect on gingival overgrowth and to study the factors affecting it. MATERIALS AND METHODS: Three groups of 30 children each on monotherapy of phenytoin, sodium valproate, and carbamazepine were longitudinally followed for six months. Their oral and epileptic health status was assessed and were monitored for change in plaque levels, gingival inflammation, probing depth and the status of gingival overgrowth at baseline, at the end of 3 months and finally at the end of 6 months. The data was recorded and statistically analysed. RESULTS: Phenytoin caused gingival overgrowth in a significant number of children (53.6%) within 3 months. Sodium valproate also led to gingival overgrowth, but not upto statistically significant levels. Patients on carbamazepine did not show any signs of gingival overgrowth. Gingival overgrowth is seen more on buccal side, in the anterior segment and in the lower arch. No correlation could be found between, either plaque level, or gingival inflammation with gingival overgrowth. Probing depth could be positively correlated with gingival overgrowth. CONCLUSION: Phenytoin is the drug, which can be chiefly implicated for causing gingival overgrowth. Sodium valproate carries the potential for gingival overgrowth, although only up to clinically insignificant levels in 6 months. Carbamazepine can be considered a safe drug in children in relation to gingival overgrowth. PMID- 26894173 TI - An Evaluation of Retentive Ability and Deformation of Acetal Resin and Cobalt Chromium Clasps. AB - AIM: To compare the retentive ability and deformation of Acetal resin with Cobalt Chromium clasps via Insertion Removal apparatus after subjecting them to stimulate clinical use. MATERIALS AND METHODS: Materials used for this study are commercially available Cobalt-Chromium alloy namely Wironit, Bego, Germany and Acetal resin namely Biodentaplast, Bredent, Germany. The test samples were divided into two major groups based on the type of materials used in the study. Each major group is further subdivided into two sub groups based on the retentive undercut depths used to engage the clasps. So a total of 20 specimens were prepared, comprising of 5 specimens in each sub group. Then the specimens were tested for retention force and deformation. RESULTS: The results of this study indicate that acetal resin clasps are resistant to deformation and may offer a clinical advantage over the conventional metal clasps. The retentive force of acetal resin clasps did not decrease over the cycling periods. This would be attributed to the resilient nature of acetal resin. Under the conditions of the present study cobalt chromium clasps lost retentive force within 730 cycles of placement and removal and continued to lose retentive force during the remaining test period. CONCLUSION: This invitro study demonstrated that retentive force of cobalt chromium clasp is superior to that of Acetal resin for removable partial dentures. As acetal resin clasps exhibits greater flexibility and long term retentive resiliency, it can be used for removable partial dentures where aesthetics or periodontal health is a primary concern. PMID- 26894174 TI - Oral Radiology Safety Standards Adopted by the General Dentists Practicing in National Capital Region (NCR). AB - INTRODUCTION: With advancement in diagnostic techniques, the utilization of radiologic examination has risen to many folds in the last two decades. Ionizing radiations from the radiographic examination carry the potential for harm by inducing carcino-genesis in addition to the diagnostic information extracted. Radiation doses utilized in the course of dental treatment might be low for individual examinations but patients are exposed to repeated examinations very often and many people are exposed during the course of dental care. Therefore, principles of radiation protection and safety are necessary for the dentists to follow to ensure minimum and inevitable exposure. AIM: The aim of this study was to investigate the knowledge and behaviour of general dentists practicing in the National Capital Region (NCR) regarding radiation safety during oral radiographic procedures. MATERIALS AND METHODS: The study was a questionnaire based cross sectional study. A total of 500 general dentists were contacted to participate in the study. The target population entailed of general dentists practicing in the National Capital Region. Data was computed and tabulated in Microsoft excel sheet and statistical analysis was performed with the help of SPSS version 21.0. RESULTS: The total response rate recovered was 70.6% and the respondents comprised of 59% and 41% males & females respectively. Only 64.8% of the general dentists contemplated thyroid to be the most important organ for radiation protection. Only 28.8% of the general dentists followed the position & distance rule appropriately. CONCLUSION: The results showed that the knowledge and behaviour of the general dentists and the practices adopted by them regarding radiation safety is not satisfactory. To ensure the following of basic and necessary guidelines for radiation safety and protection, strict rules with penalties should be implemented by the state councils and new and interesting methods of education for this spectrum of the field should be introduced. PMID- 26894175 TI - The Efficacy of Topical Hyaluronic Acid 0.2% in the Management of Symptomatic Oral Lichen Planus. AB - INTRODUCTION: Oral lichen planus (OLP) is a condition frequently referred to the specialist dental clinic for diagnosis and management. It is a disease of the skin and mucous membranes with oral manifestations too. It varies in appearance from keratotic to erythematous and ulcerative form. Immunosuppressants are frequently used for patients but some of these drugs could be implicated in malignant transformation, thus there is a clear need to find an alternative therapy for OLP. AIM: To evaluate the relief of symptoms and reduction in the size of the lesions of lichen planus with 0.2% hyaluronic acid topical application and to compare the efficacy of topical hyaluronic acid (0.2%) with that of patients on placebo. MATERIALS AND METHODS: A randomized controlled study was conducted on 50 symptomatic and biopsy proven patients with lichen planus. The subjective symptoms like Visual Analogue Scale (VAS) and the objective symptoms like degree of erythema and mean area of the lesion were recorded preoperatively and on day 7, day 14, day 21 and day 28. The selected patients were divided randomly into group-I comprising of 25 patients who received topical 0.2% hyaluronic acid therapy for 14 days and group-II comprising of 25 patients who received topical application of placebo for 14 days. The statistical tests used were Mann-Whitney U test, t-test, Wilcoxon matched pairs test by ranks and paired t-test. RESULTS: Symptomatic effect of soreness evaluation- there was a significant reduction in VAS scores in the test group as compared to placebo, similarly there was also significant reduction in the degree of erythema, change in the size of the lesion and area of the lesion in the test group. There was significant improvement in relief of symptoms, in the degree of erythema and mean area of the lesion in Group-I when compared with group-II. CONCLUSION: Topical application of 0.2% Hyaluronic acid showed a significant clinical response when compared to topical placebo. It is easy to use; hence a frequent application scheme should be advised to improve the efficacy of hyaluronic acid. PMID- 26894177 TI - Comparative Evaluation of Antifungal Effect of Titanium, Zirconium and Aluminium Nanoparticles Coated Titanium Plates Against C. albicans. AB - INTRODUCTION: The topographical modifications may vary from millimeter wide grooves to nano size structures. Recently growing nano technology is rapidly advancing surface engineering in implant dentistry. This advancement has resulted in difference in surface properties including the morphology, chemistry, crystal structure and mechanical properties of the implant. AIM: To evaluate the anticandidal effect of titanium, zirconium and aluminium nanoparticles against C. albicans at 24 hours, 72 hours and one week time interval. MATERIALS AND METHODS: According to ISO/TR 11175:1993, the samples were prepared with the dimension of 20mm diameter and 1mm thickness in grade IV titanium. A total of 40 samples were made and the samples were divided into four groups. The samples without coating were Group-A (control), samples coated with titanium nano particles were Group-B, samples coated with zirconium nano particles were Group-C and samples coated with aluminium nano particles were Group-D. The samples were cleaned by sonicating in acetone and subsequently in water three times for 15 min. Then they were treated with TiO2, ZrO2 and Al2O3 nanoparticles. The discs were sterilized under uv radiation and placed in SDA for C.albicans. The colonies were counted in 24, 72 hours and one week intervals. RESULTS: The values were statistically analyzed using one-way ANOVA and Tukey HSD Test. Significance p-value was < .001, which showed that significant difference in C.F.U among the groups in titanium coated samples at 24 hours, 72 hours and one week time intervals. CONCLUSION: TiO2 nanoparticles coated titanium plates showed significant anticandidal effect compared to ZrO2 and Al2O3 nanoparticles at 24, 72 hours and one week time interval. PMID- 26894176 TI - Aesthetic Crown Lengthening Using Chu Aesthetic Gauges And Evaluation of Biologic Width Healing. AB - INTRODUCTION: The principles of biologic width have governed the literature and served as a clinical guideline during the evaluation of perio- restorative interrelationships. An adequate understanding of this concept is paramount to ensure adequate form, function, aesthetics and comfort of the dentition. Biologic width violation has become a common problem as most of the practitioners tend to underestimate the amount of tooth structure that must be exposed during a crown lengthening procedure. Also, adding to the confusion, there is a lack of general agreement regarding the amount of tooth structure that must be exposed above the crest of bone for restorative purposes. AIM: The aim of this study was to perform aesthetic crown lengthening using Chu aesthetic gauges and evaluate the healing of biologic width. MATERIALS AND METHODS: A total of 90 teeth in 15 patients were included into the study of which 30 teeth required crown lengthening and 60 teeth shared a proximal surface with the experimental teeth. Aesthetic crown lengthening was performed using the Chu aesthetic gauges. Presurgical and intraoperative data were recorded at baseline, three and six months at six sites per tooth. RESULTS: The computed data suggest that although the positional changes of the periodontal tissues stabilize by three months, the biologic width if adequate crown lengthening is carried out re-establishes itself by three months to the original vertical levels and further gets stabilized by six months. CONCLUSION: A step by step approach to periodontal aesthetic crown lengthening using Chu aesthetic gauge can serve to be vital for successful, predictable, and aesthetic restorative outcome. PMID- 26894178 TI - Assessment of Salivary Gland Function Using Salivary Scintigraphy in Pre and Post Radioactive Iodine Therapy in Diagnosed Thyroid Carcinoma Patients. AB - INTRODUCTION: Thyroid carcinoma represents less than 1% of all cancers. The first line of treatment for thyroid cancer is partial/total thyroidectomy. High-dose Iodine(131) therapy using Iodine radioisotopes is commonly used in patients with well differentiated thyroid carcinoma after total thyroidectomy. In this process, the non-thyroidal tissues, such as, salivary gland, stomach and breast tissues also take up radioactive iodine. Salivary gland scintigraphy is widely accepted as a sensitive and valid method for evaluation of salivary gland dysfunction after Radioactive Iodine(131) Therapy (RIT). AIM: To assess and compare the salivary flow rates, relative uptake and ejection fractions in parotid and submandibular glands just before and one month after Iodine(131) therapy. MATERIALS AND METHODS: The study was conducted on 24 patients diagnosed with well differentiated thyroid carcinoma who underwent partial/total thyroidectomy and were due for radioactive iodine therapy. These patients were divided into two groups based on the lesion based dosimetry (Group A: 60-100Gy; Group B: 100 150Gy). Salivary gland assessment was done by salivary gland scintigraphy before and after RIT. STATISTICAL ANALYSIS: The data collected was tabulated and statistically analysed using SPSS software version16 using paired t-test and individual sample t-test. RESULTS: A statistically significant difference in the uptake percent and ejection fraction percent in the parotid and submandibular glands before RIT and one month after RIT was observed in the study. CONCLUSION: We inferred from the study that there was an overall decrease in uptake percent and ejection fraction percent one month post RIT in both parotid and submandibular glands. Also, a statistically significant difference was noted in the uptake and ejection fraction percent between Group A and Group B concluding the fact that the damage is dose related. PMID- 26894179 TI - Evaluation of Salivary Nitric Oxide Levels in Smokers, Tobacco Chewers and Patients with Oral Lichenoid Reactions. AB - INTRODUCTION: Nitric oxide (NO), a free radical, acts as a signalling molecule affecting numerous physiological and pathological processes. Role of nitric oxide as a mediator in tobacco related habits and the resultant oral lichenoid reactions was assessed. AIM: The aim of the study is to evaluate and compare the salivary nitric oxide levels in normal patients with that of smokers, tobacco chewers and patients with oral lichenoid reactions. MATERIALS AND METHODS: One hundred and twenty patients were enrolled in the study which included 30 healthy patients without any chronic inflammatory lesion and habit as controls (group I), 30 smokers without the habit of tobacco/betel nut chewing and any oral lesion (group II), 30 tobacco chewers without the habit of smoking and any oral lesion (group III) and 30 histologically confirmed cases of oral lichenoid reaction with the habit of tobacco usage (group IV). Saliva from these patients was collected and the nitrite concentration was assessed. RESULTS: Our results concluded that there was highly significant increase in the nitric oxide levels in smokers, tobacco chewers and patients with oral lichenoid reactions compared to that of controls. Also, there was a significant increase in nitric oxide levels in patients with smoking associated oral lichenoid reactions in comparison with smokers and in patients with lichenoid reactions associated with tobacco chewing in comparison with tobacco chewers. CONCLUSION: Estimation of salivary nitric oxide levels is a simple, non-invasive procedure and could be analysed to suggest the role of nitric oxide in the pathogenesis of these lesions. The increased activity of the enzyme may indicate that nitric oxide has a pathophysiological role in these lesions. PMID- 26894180 TI - Clinical Evaluation of Low Level Diode Laser Application For Primary Teeth Pulpotomy. AB - INTRODUCTION: Inspite of latest advances in the materials and techniques practiced for the treatment of pulpally infected teeth with better reported success rate, still the question arises for safety and effectiveness of these medicaments. AIM: The objective of the present study was to compare the effectiveness of the Low Level Laser Therapy to Mineral Trioxide Aggregate (MTA) when used for pulpotomy in vital human primary molars. MATERIALS AND METHODS: The sample consisted of 40 primary molars from 29 children aged four to seven years. The teeth were selected based on clinical, radiographic criteria and randomly allocated to two groups. All the 40 primary molars were subjected to standard pulpotomy procedure, where in 20 molars received MTA (Group I) and 20 molars received LLLT (Group II) pulpotomy. Children were recalled at 3, 6 and 12 months intervals and pulpotomised molars were examined clinically and radiographically. Data was analysed using chi-square test. RESULTS: MTA showed 94.7% success rate at all the three intervals, where as LLLT showed a success of 95% at three months, which decreased gradually to 85% at six months and 80% at 12 months. Intergroup comparisons were not significant. CONCLUSION: Low level laser therapy can be considered for primary teeth pulpotomy and its success is comparable to MTA pulpotomy technique. PMID- 26894181 TI - ZACD: A Retrograde Panoramic Analysis among Indian Population with New System of Classification. AB - INTRODUCTION: Zygomatic Air Cell Defect (ZACD) has been considered as a normal radiographic variant with a spare knowledge. This should be judged before any surgical procedure of the temporal region as lack of which can lead to infections of cranium and may other complications. AIM: The present study was undertaken to estimate the prevalence and characteristics of ZACD and to propose a classification for the same using digital panoramic radiography. MATERIALS AND METHODS: A total of 6825 digital panoramic radiographs were evaluated retrospectively of subjects aged between 4-90 years from both genders. The radiographs were evaluated by 4 (four) oral radiologists and the ZACD was recorded only when the decision was indisputable. RESULTS: Out of 6825 digital panoramic radiographs evaluated ZACD was noticed in 133 subjects with an overall prevalence of 1.94%. A male predilection was noted in the present study with the maximum prevalence during the second, third and fourth decade of life and as the age increases its prevalence decreases. Most commonly it was found to be unilateral and the unilocular presentation being more common. CONCLUSION: Most of the finding of the present study is in acceptance with those conducted previously, but some of the finding contradicts those in the previous ones. It can be because of low sample size of the previous studies. Moreover this study gives a new system to classify these defects to help diagnose the nature of the defect. PMID- 26894182 TI - The Effects of In-Office Reconditioning on the Slot Dimensions and Static Frictional Resistance of Stainless Steel Brackets. AB - INTRODUCTION: Orthodontists are commonly faced with the decision of what to do with loose brackets, and with inaccurately located brackets that need repositioning during treatment. One solution is to recycle the brackets. The potential effects of reconditioning a bracket are dependent upon many factors which may result in physical changes like alteration in slot tolerance, which may influence sliding mechanics by affecting frictional resistance. AIM: To study and compare the dimensional changes in the bracket slot width and depth in reconditioned brackets from unused brackets under scanning electronic microscope and to study and compare any consequent effects on the static frictional resistance of stainless steel brackets after reconditioning and in unused brackets. MATERIALS AND METHODS: Dentarum manufactured 90 stainless steel central incisors edgewise brackets of size 0.22 X 0.030" inch and 0 degrees tip and 0 degrees angulation were taken. 60 samples for measuring frictional resistance and 30 samples for measuring slot dimensions. Ortho organizers manufactured stainless steel arch wires 0.019 X 0.025" straight lengths 60 in number were considered for measuring static frictional resistance. RESULTS: The mean slot width and depth of new brackets were 0.0251" and 0.0471", which exceeded the manufacturers reported nominal size of 0.022" X 0.030", by 0.003" and 0.017". The reconditioned brackets demonstrated a further increase in mean slot width and depth to 0.028" and 0.0518" that is by 0.0035" and 0.0047" which is statistically significant (p=0.001, 0.002). The mean static frictional forces of the reconditioned brackets was nearly similar to that of new brackets that is 0.3167N for reconditioned brackets and 0.2613 N for new brackets. CONCLUSION: Although the reconditioning process results in physical changes to bracket structure this does not appear to result in significant effect on ex-vivo static frictional resistance. PMID- 26894183 TI - An Evaluation of Upper and Lower Pharyngeal Airway Width, Tongue Posture and Hyoid Bone Position in Subjects with Different Growth Patterns. AB - INTRODUCTION: It is important to evaluate the position of the hyoid bone in relation to the tongue at the beginning of orthodontic treatment so that during the treatment, its position may be directed hence overall impact on airway could be assessed. AIM: The aim of this study was to evaluate the upper and lower pharyngeal airway dimensions, posture of tongue and hyoid bone position in young adults with different growth patterns. MATERIALS AND METHODS: Sample size of the study included 90 post-adolescent subjects, within the age range of 18-32 years. Based on the different growth pattern of the face, subjects were divided into Group I (n=30; average growth pattern), Group II (n=30; horizontal growth pattern) and Group III (n=30; vertical growth pattern). Lateral cephalogram were traced and analysed manually by the same investigator for evaluation of upper and lower pharyngeal airway, tongue posture and hyoid bone position. The intergroup comparison of upper and lower pharyngeal airway dimensions, posture of tongue and hyoid bone was performed with one-way ANOVA test. RESULTS: The results showed that upper oropharyngeal widths were significantly different in different facial skeletal patterns (p=0.00). Subjects with vertical skeletal pattern have significantly narrower upper airways than those with horizontal skeletal pattern (p= 0.025). There was significantly higher difference in position of dorsum of the tongue in vertical growth pattern group (p=0.00). The hyoid bone was positioned farther from the mandibular symphysis in brachyfacial subjects, reflected by the larger H-RGN (Hyoid- retrognathion) values compared with the dolichofacial and normal subjects (p=0.044). CONCLUSION: The upper oropharyngeal width was found to be narrower in subjects with vertical growth pattern. The dorsum of the tongue is seen to be placed higher in subjects with vertical growth pattern. The hyoid bone was more inferiorly and posteriorly positioned in subjects with horizontal growth pattern. Variations are seen in upper and lower oropharyngeal widths, posture of the tongue and hyoid bone position in all the growth patterns. PMID- 26894184 TI - Pleomorphic Adenoma in Retromolar Area: A Very Rare Case Report and Review of Literature. AB - Among all neoplasms affecting head and neck region, salivary gland neoplasms are rare. Pleomorphic adenomas are the most common benign salivary gland tumours making up to 50% of major and minor salivary gland tumours. Intraorally pleomorphic adenoma is mostly found on palate and lips and very rarely in retromolar area. Here we are reporting a rare case of pleomorphic adenoma in right lower retromolar area in a 31-year-old female, the lesion was excised in toto with safety margins under local anaesthesia and postoperative follow up after six months didn't showed any recurrence. PMID- 26894185 TI - Ameloblastic Fibrodentinoma: Report of a Case in an Infant. AB - Ameloblastic fibrodentinoma (AFD) is a debatable neoplasm with respect to its clinical, biological and histopathological diagnosis. The clinical and radiological presentation may mimic ameloblastic fibro odontoma, odontoma, ameloblastic fibroma and cemento-ossifying fibroma. We report an interesting case of AFD occurring in canine region of mandible in a one-year-old infant. From a review of English language literature, to the best of our knowledge this is the first case occurring in an infant. The purpose of this case report is to create awareness among the clinicians to make the best possible management of this controversial pathologic entity. PMID- 26894186 TI - Ackerman's Tumour - A Case Report. AB - Ackerman's tumour or Verrucous Carcinoma (VC) is a distinct form of Squamous Cell Carcinoma (SCC). It is predominantly seen in elderly men and strongly associated with the use of tobacco. In oral cavity it occurs predominantly in buccal mucosa followed by gingiva, palate and floor of the mouth. Clinically it manifests as proliferative finger like projections resembling a cauliflower which is characteristic of its diagnosis. Histologically, papillary or verruciform surface and parakeratin plugs between the surface projections are seen with an intense infiltrate of chronic inflammatory cells in the connective tissue thus it requires enormous expertize for diagnosis. Although VC is illustrated as a benign lesion with minimum aggressive potential over a period of time it can evolve into SCC. Hence most appropriate management of Ackerman's tumour is early diagnosis and surgical excision of the lesion. With this above background, we hereby report an enticing case of verrucous carcinoma in a left retromolar trigone extending into lower alveolar ridge in a 52-year-old male patient. PMID- 26894187 TI - Total Extraction as a Treatment for Anaemia in a Patient of Glanzmann's Thrombasthenia with Chronic Gingival Bleed: Case Report. AB - Glanzmann's Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder affecting the megakaryocyte lineage and is characterized by lack of platelet aggregation on stimulation. The molecular basis is linked to quantitative and qualitative abnormalities of alphaIIbbeta3 integrin. Most of the patients with severe Glanzmann's thrombasthenia have spontaneous gum bleeding and persistent low haemoglobin levels. Often these patients are addressed with local haemostatic measures and platelet coverage. We report a case of a severe Glanzmann's thrombasthenia with chronic gingivitis and associated spontaneous gum bleed with chronic low haemoglobin levels, managed subsequently with total dental extraction under appropriate platelet and recombinant factor VIIa coverage. Further follow up of the patient substantiated the treatment protocol with increased and stable haemoglobin levels, thus emphasizing the need for total dental extraction in patients with severe Glanzmann's with chronic spontaneous gum bleed, as a definitive treatment option, which has not been reported so far in the literature. PMID- 26894188 TI - Intralesional Sclerotherapy - A Novel Approach for The Treatment of Intraoral Haemangiomas. AB - In infancy and childhood haemangiomas are the most common neoplasms in head and neck region with an occurrence of about 60%. Approximately 40%-50% of all haemangiomas resolve incompletely, leaving permanent changes in the skin, such as telangiectases, epidermal atrophy, hypopigmentation or redundant skin with fibro fatty residue but a few stubborn, problematic haemangiomas may result in serious disfigurement and dysfunction, and even become life-threatening. Most haemangiomas are managed by conservative methods that include corticosteroids (either systemic or local injection), sclerotherapy, interferon-alpha, laser therapy, embolization, cryotherapy, and radiation. Due to risk of haemorrhaging, surgical removal for small vascular lesions is not considered and it is more invasive than sclerotherapy. This case report presents the efficacy of intralesional sclerotherapy for the management of haemangiomas on dorsum and lateral border of tongue. PMID- 26894189 TI - Periodontal Intervention in Speedy Orthodontics-A Case Report. AB - The use of orthodontic treatment in adult patients is becoming more common and these patients have more specific objectives and concerns related to facial and dental aesthetics, specially regarding duration of treatment. Dentists are on the lookout for techniques for increased efficiency in orthodontic treatment. Alveolar Corticotomy-assisted orthodontic treatment is a recent orthodontic technique that is recently gaining wide acceptance and is recorded as effective means of accelerating orthodontic treatment. A 17-year-old female patient was undergoing orthodontic treatment for the past one year but during her space closure, a visual examination confirmed a buccal thickening that was encountered in the buccal plate between premolars and canine. Periodontal intervention involved elective alveolar decortication in the form of dots performed around the teeth that were to be moved. This was carried out to induce a state of increased tissue turnover and a transient osteopenia, which further helps in faster rate of orthodontic tooth movement. Its main advantages are reduction of treatment time and post-orthodontic stability. PMID- 26894190 TI - Neurilemmoma of the Vagus Nerve in the Poststyloid Parapharyngeal Space. AB - We report a large vagal neurilemmoma in the poststyloid compartment of the parapharyngeal space. A 52-year-old man was referred to our hospital with a feeling of discomfort in the left upper neck. Computed tomography showed a 30mm x 30mm x 40mm mass with inhomogeneous internal enhancement in the left carotid space. Magnetic resonance imaging revealed a 30mm * 30mm * 40mm heterogeneous mass in the area of the bifurcation of the common carotid artery. We gave a provisional diagnosis of neurilemmoma or vagal paraganglioma in the parapharyngeal space preoperatively based on the results of physical examination and imaging. We selected a transcervical-transmandibular approach. Under general anaesthesia, a tumour originating from the vagus nerve was completely extirpated while protecting the internal and external carotid arteries. Although mild postvagotomy dysphagia and hoarseness were seem for 6 months postoperatively, symptoms resolved and the patient showed a satisfactory course without recurrence after 10 years. Histological examination of the excised specimen showed antoni A and antoni B pattern. Positive immunoreactivity for S-100 protein was identified, but negative results were obtained for neuron-specific enolase, chromogranin and neurofilament. The tumour was diagnosed as neurilemmoma of the vagus nerve. PMID- 26894191 TI - Direct Sinus Lift and Immediate Implant Placement Using Piezosurgical Approach- A Case Report. AB - Numerous studies have shown that placement of implants in the maxillary region with resultant successful osseointegration can be achieved by the use of sinus lift procedures using piezosurgical technique. In this case report a middle aged patient had come to the outpatient department of A. J. Institute of Dental Sciences with a chief complaint of missing right posterior molar. Since the radiographic ball marker showed only 4 mm bone below the sinus in #16 region, direct sinus lift procedure was done for placement of a dental implant. Piezosurgery was performed, as it reduces the risk of damaging vital soft tissues such as nerves, dura matter and blood vessels. To stabilize the implant in the maxillary sinus region and also to stimulate bone regeneration, gamma irradiated cancellous allograft was used. Periapical radiographs were taken 10 months after implant placement which showed good bone growth over the implant collar. Bone formation in the maxillary antrum was seen clearly in the panoramic radiograph. Using piezosurgical unit, sinus lift procedure with sinus grafting proved to be less traumatic and more successful. PMID- 26894192 TI - Management of Chronic Hyperplastic Pulpitis in Mandibular Molars of Middle Aged Adults- A Multidisciplinary Approach. AB - The molar tooth of children and young adults is a common site for chronic hyperplastic pulpitis (pulp polyp). It rarely occurs in middle aged adults. This condition is usually characterized by extensive involvement of the pulp, dictating the extraction of involved tooth. Extraction of permanent molars can lead to transient or permanent malocclusion, aesthetic, phonetic and functional problems. Here we report a case of pulp polyp in mandibular first molar of a 33 year-old woman that grew into the carious cavity. The aim of this case report is to describe the diagnosis of a chronic hyperplastic pulpitis involving the permanent molar as well as to describe its management in order to preserve them as a functional unit of the dentition. PMID- 26894193 TI - Head Injury- A Maxillofacial Surgeon's Perspective. AB - Injuries and violence are one of the leading causes of mortality worldwide. A substantial portion of these injuries involve the maxillofacial region. Among the concomitant injuries, injuries to the head and cervical spine are amongst those that demand due consideration on account of their life threatening behaviour. Studies have shown that facial fractures have a strong association with traumatic brain injury. Knowledge of the types and mechanisms of traumatic brain injury is crucial for their treatment. Many a times, facial fractures tend to distract our attention from more severe and often life threatening injuries. Early diagnosis of these intracranial haemorrhage leads to prompt treatment which is essential to improve the outcome of these patients. An oral and maxillofacial surgeon should be able to suspect and diagnose head injury and also provide adequate initial management. PMID- 26894194 TI - Clinical Tip for Adjusting Reverse Pull Facemask/Headgear Assembly. AB - Point of force application is critical in predicting the result of reverse pull headgear assembly. Different people have suggested different point of force application. A clinical tip is provided for adjusting the hook of intraoral stabilizing appliance, so that it rests on zero moment line which helps in translatory movement of maxilla. Simple and effective clinical method of adjusting the reverse pull headgear is illustrated here along with its biomechanical justification. PMID- 26894195 TI - Supplemental Maxillary Permanent Central Incisor or Macrodontia of Lateral Incisor! A Diagnostic Challenge. PMID- 26894196 TI - Crouzon Syndrome: Report in a Family. PMID- 26894197 TI - Clinico-Radiologic Perspective of a Case of Hemifacial Microsomia. PMID- 26894198 TI - Images in Medicine - Hajdu-Cheney Syndrome: A Rare Case Report. PMID- 26894199 TI - A 13-Month-Old With Xanthogranulomatous Pyelonephritis With Features of Renal Malakoplakia. AB - Xanthogranulomatous pyelonephritis is an uncommon chronic inflammatory renal disorder caused by chronic infection with gram-negative bacteria leading to destruction of the renal parenchyma and replacement with foamy lipid-laden macrophages. Renal malakoplakia is another rare form of chronic inflammatory granulomatous disease in the kidney associated with infection usually occurring in adults with immunocompromised status or debilitating disease. It is hallmarked by the finding of foamy histiocytes with distinctive basophilic inclusions (Michaelis-Gutmann bodies). We present a case of a 13-month-old male with history of congenital hydronephrosis who presented with clinical and radiologic findings suggestive of xanthogranulomatous pyelonephritis. However, further pathologic studies revealed the presence of Michaelis-Gutmann bodies, which are pathognomonic for renal malakoplakia. With this case we hope to bring further evidence to support that these two conditions are not mutually exclusive but rather represent two pathologic processes on the same disease spectrum. PMID- 26894200 TI - Adaptation Strategies of Individuals With Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Despite the strong implications for rehabilitation design, the capability of individuals with anterior cruciate ligament reconstruction (ACLR) to adapt and store novel gait patterns have not been well studied. PURPOSE: To investigate how reconstructive surgery may affect the ability to adapt and store novel gait patterns in persons with ACLR while walking on a split-belt treadmill. STUDY DESIGN: Controlled laboratory study. METHODS: Gait adaptation was compared between 20 participants with ACLR and 20 healthy controls during split-belt treadmill walking. Gait adaptation was assessed in slow- and fast-adapting parameters by (1) the magnitude of symmetry during late adaptation and (2) the amount of the asymmetry during de-adaptation. RESULTS: Healthy individuals adapted a new walking pattern and stored the new walking pattern equally in both the dominant and nondominant limbs. Conversely, individuals with ACLR displayed impairments in both slow-adapting and fast-adapting derived gait adaptation and significant differences in behavior between the reconstructed and uninjured limb. CONCLUSION: While surgical reconstruction and physical therapy are aimed at improving mechanical stability to the knee, the study data suggest that fundamental features of motor control remain altered. After ACLR, participants display an altered ability to learn and store functional gait patterns. PMID- 26894201 TI - Histoplasmosis-Associated Hospitalizations in the United States, 2001-2012. AB - We examined trends in histoplasmosis-associated hospitalizations in the United States using the 2001-2012 National (Nationwide) Inpatient Sample. An estimated 50 778 hospitalizations occurred, with significant increases in hospitalizations overall and in the proportion of hospitalizations associated with transplant, diabetes, and autoimmune conditions often treated with biologic therapies; therefore, histoplasmosis remains an important opportunistic infection. PMID- 26894202 TI - An interesting variety. PMID- 26894203 TI - Visual dysfunction, but not retinal thinning, following anti-NMDA receptor encephalitis. AB - OBJECTIVE: To assess structural and functional changes in the afferent visual system following anti-NMDA receptor (NMDAR) encephalitis. METHODS: In this cross sectional study including 31 patients after acute NMDAR encephalitis and matched healthy controls, visual function was assessed as high-contrast visual acuity using Early Treatment Diabetic Retinopathy Study charts and low-contrast sensitivity using Functional Acuity Contrast Test. Retinal changes were measured using optical coherence tomography with assessment of peripapillary retinal nerve fiber layer (pRNFL) and macular intraretinal layer thicknesses. Residual clinical impairment was described using the modified Rankin Scale. RESULTS: High-contrast (logMAR 0.02 +/- 0.14 vs -0.09 +/- 0.14, p < 0.001) and low-contrast (area under the curve 1.89 +/- 0.21 vs 2.00 +/- 0.26, p = 0.039) visual acuity were reduced in patients in comparison to healthy controls. More severely affected patients performed worse in visual acuity testing than patients with good recovery (logMAR -0.02 +/- 0.11 vs 0.08 +/- 0.17, p = 0.030). In contrast, patients did not differ from matched healthy controls in pRNFL or in thickness of intraretinal layers, including the ganglion cell complex, the inner nuclear layer, the outer nuclear and plexiform layers, and the photoreceptor layer. CONCLUSIONS: After acute NMDAR encephalitis, patients have mild visual dysfunction in comparison to matched healthy controls, while retinal structure appears unaltered. These observations could point to an impairment of anterior or posterior visual pathway NMDAR function that is similar to dysfunction of NMDAR in cerebral cortex and subcortical structures. Alternatively, residual cognitive impairment might reduce visual function. PMID- 26894204 TI - Serum lipid antibodies are associated with cerebral tissue damage in multiple sclerosis. AB - OBJECTIVE: To determine whether peripheral immune responses as measured by serum antigen arrays are linked to cerebral MRI measures of disease severity in multiple sclerosis (MS). METHODS: In this cross-sectional study, serum samples were obtained from patients with relapsing-remitting MS (n = 21) and assayed using antigen arrays that contained 420 antigens including CNS-related autoantigens, lipids, and heat shock proteins. Normalized compartment-specific global brain volumes were obtained from 3-tesla MRI as surrogates of atrophy, including gray matter fraction (GMF), white matter fraction (WMF), and total brain parenchymal fraction (BPF). Total brain T2 hyperintense lesion volume (T2LV) was quantified from fluid-attenuated inversion recovery images. RESULTS: We found serum antibody patterns uniquely correlated with BPF, GMF, WMF, and T2LV. Furthermore, we identified immune signatures linked to MRI markers of neurodegeneration (BPF, GMF, WMF) that differentiated those linked to T2LV. Each MRI measure was correlated with a specific set of antibodies. Strikingly, immunoglobulin G (IgG) antibodies to lipids were linked to brain MRI measures. Based on the association between IgG antibody reactivity and each unique MRI measure, we developed a lipid index. This comprised the reactivity directed against all of the lipids associated with each specific MRI measure. We validated these findings in an additional independent set of patients with MS (n = 14) and detected a similar trend for the correlations between BPF, GMF, and T2LV vs their respective lipid indexes. CONCLUSIONS: We propose serum antibody repertoires that are associated with MRI measures of cerebral MS involvement. Such antibodies may serve as biomarkers for monitoring disease pathology and progression. PMID- 26894205 TI - Cytokine profiles show heterogeneity of interferon-beta response in multiple sclerosis patients. AB - OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-beta treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-beta treatment were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays. Baseline cytokine profiles were grouped by hierarchical clustering analysis. Demographic features, changes in cytokines, and clinical outcome were then assessed in the clustered patient groups. RESULTS: A total of 157 patients were included in the study and clustered into 6 distinct subsets by baseline cytokine profiles. These subsets differed significantly in their clinical and biological response to IFN beta therapy. Two subsets were associated with patients who responded poorly to therapy. Two other subsets, associated with a good response to therapy, showed a significant reduction in relapse rates and no worsening of disability. Each subset also had differential changes in cytokine levels after 3 months of IFN beta treatment. CONCLUSIONS: There is heterogeneity in the immunologic pathways of the RRMS population, which correlates with IFN-beta response. PMID- 26894206 TI - Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis. AB - OBJECTIVE: To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)-positive and negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS). METHODS: We screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20). RESULTS: Differential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD. CONCLUSIONS: While AQP4-Ab-positive and negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS. PMID- 26894207 TI - Autopsy-proven demyelination associated with infliximab treatment. PMID- 26894208 TI - Degos disease mimicking primary vasculitis of the CNS. PMID- 26894209 TI - Direct Care Worker Training to Respond to the Behavior of Individuals With Dementia: The CARES(r) Dementia-Related BehaviorTM Online Program. AB - Only a handful of online training programs are available for direct care workers (DCWs) to acquire the strategic skills needed to improve dementia care in instances of challenging or inappropriate behavior. Utilizing pre- and post-test data from a convenience sample of 40 DCWs, the present study sought to determine (a) whether DCWs' knowledge of responding to dementia-related behavior increased following participation in the CARES(r) Dementia-Related BehaviorTM Online Training Program (or CARES(r) Behavior) and (b) if CARES(r) Behavior was acceptable and useful. The average number of correct scores on a dementia care knowledge measure was significantly higher among DCWs after viewing the online modules when compared with pre-test scores (p < .01). Descriptive empirical and open-ended data also suggested that the interactive, "real-world" content of CARES(r) Behavior was feasibly delivered online, acceptable, and may influence how DCWs deliver clinical care to individuals with dementia-related behavior. PMID- 26894210 TI - The World Learns Together. PMID- 26894212 TI - Operating Room Time Savings with the Use of Splint Packs: A Randomized Controlled Trial. AB - BACKGROUND: The most expensive variable in the operating room (OR) is time. Lean Process Management is being used in the medical field to improve efficiency in the OR. Streamlining individual processes within the OR is crucial to a comprehensive time saving and cost-cutting health care strategy. At our institution, one hour of OR time costs approximately $500, exclusive of supply and personnel costs. Commercially prepared splint packs (SP) contain all components necessary for plaster-of-Paris short-leg splint application and have the potential to decrease splint application time and overall costs by making it a more lean process. We conducted a randomized controlled trial comparing OR time savings between SP use and bulk supply (BS) splint application. METHODS: Fifty consecutive adult operative patients on whom post-operative short-leg splint immobilization was indicated were randomized to either a control group using BS or an experimental group using SP. One orthopaedic surgeon (EMB) prepared and applied all of the splints in a standardized fashion. Retrieval time, preparation time, splint application time, and total splinting time for both groups were measured and statistically analyzed. RESULTS: The retrieval time, preparation time and total splinting time were significantly less (p<0.001) in the SP group compared with the BS group. There was no significant difference in application time between the SP group and BS group. CONCLUSION: The use of SP made the process of splinting more lean. This has resulted in an average of 2 minutes 52 seconds saved in total splinting time compared to BS, making it an effective cost cutting and time saving technique. For high volume ORs, use of splint packs may contribute to substantial time and cost savings without impacting patient safety. PMID- 26894211 TI - Giant Cell Tumor of Bone - An Overview. AB - Giant Cell tumors (GCT) are benign tumors with potential for aggressive behavior and capacity to metastasize. Although rarely lethal, benign bone tumors may be associated with a substantial disturbance of the local bony architecture that can be particularly troublesome in peri-articular locations. Its histogenesis remains unclear. It is characterized by a proliferation of mononuclear stromal cells and the presence of many multi- nucleated giant cells with homogenous distribution. There is no widely held consensus regarding the ideal treatment method selection. There are advocates of varying surgical techniques ranging from intra-lesional curettage to wide resection. As most giant cell tumors are benign and are located near a joint in young adults, several authors favor an intralesional approach that preserves anatomy of bone in lieu of resection. Although GCT is classified as a benign lesion, few patients develop progressive lung metastases with poor outcomes. Treatment is mainly surgical. Options of chemotherapy and radiotherapy are reserved for selected cases. Recent advances in the understanding of pathogenesis are essential to develop new treatments for this locally destructive primary bone tumor. PMID- 26894214 TI - Type II Intertrochanteric Fractures: Proximal Femoral Nailing (PFN) Versus Dynamic Hip Screw (DHS). AB - BACKGROUND: Intertrochanteric fracture is one of the most common fractures of the hip especially in the elderly with osteoporotic bones, usually due to low-energy trauma like simple falls. Dynamic Hip Screw (DHS) is still considered the gold standard for treating intertrochanteric fractures by many. Not many studies compare the DHS with Proximal femoral nail (PFN), in Type II intertrochanteric fractures (Boyd and Griffin classification). This study was done to compare the functional and radiological outcome of PFN with DHS in treatment of Type II intertrochanteric fractures. METHODS: From October 2012 to March 2015, a prospective comparative study was done where 30 alternative cases of type II intertrochanteric fractures of hip were operated using PFN or DHS. Intraoperative complications were noted. Functional outcome was assessed using Harris Hip Score and radiological findings were compared at 3, 6, and 12 months postoperatively. RESULTS: The average age of the patients was 60 years. In our series we found that patients with DHS had increased intraoperative blood loss (159ml), longer duration of surgery (105min), and required longer time for mobilization while patients who underwent PFN had lower intraoperative blood loss (73ml), shorter duration of surgery (91min), and allowed early mobilization. The average limb shortening in DHS group was 9.33 mm as compared with PFN group which was only 4.72 mm. The patients treated with PFN started early ambulation as they had better Harris Hip Score in the early post-op period. At the end of 12th month, there was not much difference in the functional outcome between the two groups. CONCLUSION: PFN is better than DHS in type II intertrochanteric fractures in terms of decreased blood loss, reduced duration of surgery, early weight bearing and mobilization, reduced hospital stay, decreased risk of infection and decreased complications. PMID- 26894213 TI - The Effect of the Silicone Ring Tourniquet and Standard Pneumatic Tourniquet on the Motor Nerve Conduction, Pain and Grip Strength in Healthy Volunteers. AB - BACKGROUND: The pneumatic tourniquet (PT) is routinely used in upper and lower limb operations by most orthopaedic surgeons. The silicone ring tourniquet (SRT) was introduced in clinical practice over the last decade. Clinical as well as comparative studies have been published in volunteers concerning its safety and efficacy. The aim of this study was to investigate the postoperative effect of the silicone ring tourniquet (SRT), primarily on the motor nerve conduction, and secondarily on the pain and grip strength, in comparison to the effect of the pneumatic tourniquet (PT) in healthy volunteers. METHODS: Both tourniquets were applied in the forearm of the dominant arm in 20 healthy volunteers and were kept on for 10 minutes. Pain was measured using the visual analogue scale and grip strength was measured with a hand dynamometer. We evaluated the following parameters of median nerve conduction: motor conduction velocity (MCV), latency (LAT) and amplitude (AMP). RESULTS: Pain score at the time of tourniquet application was higher in SRT group but the alteration in pain scores in PT group was higher, with statistical significance (P<0.05). The grip strength was reduced by the application of both tourniquets; however there was a significantly higher reduction in the SRT group (P<0.05). The conduction impairment of the median nerve was worse in the PT group than in the SRT one, according to the changes in MCV (P<0.05). CONCLUSION: Median nerve conduction was affected more after PT application as compared to the SRT. Nevertheless, the reduction of grip strength was higher after the SRT application. PMID- 26894215 TI - Supracondylar Osteotomy in Valgus Knee: Angle Blade Plate Versus Locking Compression Plate. AB - BACKGROUND: There are few studies comparing the biomechanical properties of angled blade plate and locking compression plates in supracondylar osteotomy. In the current randomized study, we prospectively compared the clinical and radiological outcomes of supracondylar osteotomy using these two plates. METHODS: Forty patients with valgus knee malalignment were randomly assigned to two equal numbered groups: angled blade plate and locking compression plates. All of the patients underwent medial closing wedge supracondylar osteotomy and were followed for one year. Before and after the operation the valgus angle and mechanical lateral distal femoral angle were compared between groups. Also, the rate of complications were compared. RESULTS: After the operation, the mean valgus angle and mechanical lateral distal femoral angle improved significantly in the two groups (P<0.001). Although, the preoperative amount of the valgus angle and mechanical lateral distal femoral angle were the same, at the last visit the valgus angle (5.4+/-2.1 versus 3.1+/-1.8; P=0.032) and mechanical lateral distal femoral angle (87.6+/-2 versus 89.7+/-3.2; P=0.041) were significantly lower and higher in the angled blade plate group, respectively. Nonunion occurred in four patients (20%) in the locking compression plates group (P=0.35). CONCLUSION: Based on having a larger valgus angle and mechanical lateral distal femoral angle correction in the angled blade plate group and considerable rate of nonunion in the locking compression plate group, the authors recommend using the angled blade plate for fixation of medial closing wedge supracondylar osteotomy for patients with valgus malalignment. However, more long-term studies are required. PMID- 26894216 TI - Sleep Disturbance and Upper-Extremity Disability. AB - BACKGROUND: Although upper-extremity disability correlates with psychosocial aspects of illness the association with sleep disturbance in upper extremity disability is less certain. To evaluate whether sleep disturbance is associated with upper-extremity disability among patients with upper extremity illness, accounting for sociodemographic, condition-related, and psychosocial factors. METHODS: A cohort of 111 new or follow-up patients presenting to an urban academic hospital-based hand surgeon completed a sociodemographic survey and measures of sleep disturbance (PROMIS Sleep Disturbance), disability (PROMIS Upper-Extremity Physical Function), ineffective coping strategies (PROMIS Pain Interference), and depression (PROMIS Depression). Bivariate and multivariable linear regression modeling were performed. RESULTS: Sleep disturbance correlated with disability (r=-0.38; P<0.001) in bivariate analysis. Symptoms of depression (r=-0.44; P<0.001) and ineffective coping strategies (r=-0.71; P<0.001) also correlated with upper-extremity specific disability in bivariate analysis. Pain Interference was the only factor associated with disability in multivariable analysis. CONCLUSIONS: Sleep disturbance is not as strongly or directly associated with symptom intensity and magnitude of disability as ineffective coping strategies. Interventions to reduce pain interference (e.g. cognitive behavioral therapy) hold great potential to decrease musculoskeletal symptom intensity and magnitude of disability, and perhaps even sleep disturbance. PMID- 26894217 TI - Double-button Fixation System for Management of Acute Acromioclavicular Joint Dislocation. AB - BACKGROUND: Surgical treatments for acromioclavicular (AC) joint dislocation present with some complications. The present study was designed to evaluate the double-button fixation system in the management of acute acromioclavicular joint dislocation. METHODS: This cross sectional study, done between February 2011 to June 2014, consisted of 28 patients who underwent surgical management by the double-button fixation system for acute AC joint dislocation. Age, sex, injury mechanism, dominant hand, side with injury, length of follow up, time before surgery, shoulder and hand (DASH), constant and visual analogue scale (VAS) scores, and all complications of the cases during the follow up were recorded. RESULTS: The mean age of patients was 33.23+/-6.7 years. Twenty four patients (85.71%) were male and four (14.28%) were female. The significant differences were observed between pre-operation VAS, constant shoulder scores and post operation measurements. There were not any significant differences between right and left coracoclavicular, but two cases of heterotrophic ossifications were recorded. The mean follow-up time was 16.17+/-4.38 months. CONCLUSION: According to the results, the double-button fixation system for management of acute acromioclavicular joint dislocation has suitable results and minimal damage to the soft tissues surrounding the coracoclavicular ligaments. PMID- 26894218 TI - Treatment Outcome of Intramedullary Fixation with a Locked Rigid Nail in Humeral Shaft Fractures. AB - BACKGROUND: The aim of this study was to determine the treatment outcome of humeral shaft fractures with a locked rigid intramedullary nail in patients indicated for surgical treatment. METHODS: In this descriptive-cross sectional study, all patients were followed up for one, six, and 18 months post operatively. The Short Form Questionnaire (SF-36) and Constant Shoulder Score were applied. RESULTS: Of 78 included patients (mean age: 35), one patient had a soft tissue infection, one had secondary radial nerve palsy, eight had non-union, one had elbow limited range of motion in extension, and three patients had decreased shoulder range of motion. The Constant Shoulder Score and Short Form Questionnaire Score (SF-36) increased in all patients, although aged women showed lower improvement. CONCLUSION: Intramedullary nail fixation in the humeral shaft fracture may be associated with high rates of non-union. PMID- 26894220 TI - Influence of Sexuality in Functional Recovery after Spinal Cord Injury in Rats. AB - BACKGROUND: Spinal cord injury (SCI) is a major clinical condition and research is commonly done to find suitable treatment options. However, there are some degrees of spontaneous recovery after SCI and gender is said to be a contributing factor in recovery, but this is controversial. This study was done to compare the effects of sexual dimorphism on spontaneous recovery after spinal cord injury in Wistar Rats. METHODS: Spinal cord lesions were made by compressing the cord at T9 level and making a spinal cord contusion. Routine care of each rat was done daily. The LSS scoring system was used to measure the locomotion of these rats and to compare the recovery rate between male and female rats. RESULTS: The results suggested that there was no significant difference between the two sex in recovery. CONCLUSIONS: To be female does not seem to be a prognostic factor for recovery after SCI. However, this preliminary study should be repeated in other animals and in larger cohorts. PMID- 26894219 TI - Prognostic Value of Impaired Preoperative Ankle Reflex in Surgical Outcome of Lumbar Disc Herniation. AB - BACKGROUND: Several prognostic factors exist influencing the outcome of surgical discectomy in the patients with lumbar disc herniation (LDH). The aim of this study is to evaluate the relationship between severity of preoperative impaired ankle reflex and outcomes of lumbar discectomy in the patients with L5-S1 LDH. METHODS: We retrospectively evaluated 181 patients (108 male and 73 female) who underwent simple discectomy in our orthopedic department from April 2009 to April 2013 and followed them up for more than one year. The mean age of the patients was 35.3+/-8.9 years old. Severity of reflex impairment was graded from 0 to 4+ and radicular pain and disability were assessed by visual analogue scale (VAS) and Oswestry disability index (ODI) questionnaires, respectively. Subjective satisfaction was also evaluated at the last follow-up visit. Chi-square and Kruskal-Wallis tests were used to compare qualitative variables. RESULTS: Reflex impairment existed in 44.8% preoperatively that improved to 10% at the last follow-up visit. Statistical analyses could not find a significant relationship between the severity of impaired ankle reflex and sex or age (P=0.538 and P=0.709, respectively). There was a remarkable relationship between severity of reflex impairment and preoperative radicular pain or disability (P=0.012 and P=0.002, respectively). Kruskal-Wallis test showed that a more severity in ankle reflex impairment was associated with not only less improvement in postoperative pain and disability but also less satisfaction rate (P<0.001 in all three). CONCLUSIONS: In the patients with L5-S1 LDH, more severe ankle reflex impairment is associated with less improvement in postoperative pain, disability, and subjective satisfaction. PMID- 26894221 TI - How Much are Emergency Medicine Specialists' Decisions Reliable in the Diagnosis and Treatment of Pediatric Fractures? AB - BACKGROUND: Considering the importance of an early diagnosis and proper decision making in regards to the treatment of pediatric distal radius and elbow fractures, this study examines emergency medicine specialists' accuracy in the diagnosis and treatment of these patients. METHODS: From 2012 and 2013, children less than 14 years old who were referred to an academic hospital emergency department with elbow or distal radius fractures were enrolled. Initially, patients were examined by an emergency medicine specialist and then they were referred to an orthopedic surgeon. Type of fracture and the proposed treatment of two specialists were compared. RESULTS: In total, there were 108 patients (54 patients in each group) with a mean age of 8.1+/-3.3 years. Identical diagnosis in 48 cases (88.9%) of distal radius and 36 cases (66.7%) of elbow trauma were observed. We found a difference between diagnosis of the two specialists in diagnosing lateral condyle of the humerus fracture in the elbow group and growth plate fracture in the distal radius fracture group, but the differences were not significant. Among 108 patients, 70 patients (64.8%) received identical treatment. CONCLUSION: Although the emergency medicine specialists responded similarly to the orthopedic specialists in the diagnosis of pediatric distal radius and elbow fractures, diagnosis of more complicated fractures such as lateral condylar humoral fractures, distal radius growth plate and for choosing the proper treatment option, merits further education. PMID- 26894222 TI - Which Route of Tranexamic Acid Administration is More Effective to Reduce Blood Loss Following Total Knee Arthroplasty? AB - BACKGROUND: The most appropriate route of tranexamic acid administration is controversial. In the current study, we compared the efficacy of intravenous (IV) and topical intra-articular tranexamic acid in reducing blood loss and transfusion rate in patients who underwent primary total knee arthroplasty. METHODS: One hundred twenty 120 patients were scheduled to undergo primary total knee arthroplasty. Patients were randomly allocated to three equal groups: IV tranexamic acid (500 mg), topical tranexamic acid (3 g in 100 mL normal saline) and the control. In the topical group, half of the volume was used to irrigate the joint and the other half was injected intra-articularly. The volume of blood loss, hemoglobin (Hb) level at 24 hours postoperative, and rate of transfusion was compared between groups. RESULTS: The blood loss and Hb level were significantly greater and lower in the control group, respectively (P=0.031). Also, the rate of transfusion was significantly greater in the control group (P=0.013). However, IV and topical groups did not differ significantly in terms of measured variables. No patient experienced a thromboembolic event in our study. CONCLUSION: Tranexamic acid is a useful antifibrinolytic drug to reduce postoperative blood loss, Hb drop, and rate of blood transfusion in patients undergoing total knee arthroplasty. The route of tranexamic acid administration did not affect the efficacy and safety. PMID- 26894223 TI - A Survey on Transfusion Status in Orthopedic Surgery at a Trauma Center. AB - BACKGROUND: Increased costs and mortality associated with inappropriate blood transfusions have led to investigations about blood request and blood transfusion techniques. We investigated the transfusion status in patients who underwent orthopedic surgery in Poursina Hospital (Rasht, Iran) to optimizing blood usage and determine if a scheduled transfusion program for every orthopedic surgery could improve blood transfusion management. METHOD: In this descriptive prospective study, all orthopedic surgeries in Poursina Hospital, Rasht, between April to June 2013 were reviewed. All patient information was recorded, including: demographics, type of surgery, hemoglobin level, cross-match test, duration of surgery, and blood loss, and transfusion. Based on the one-way ANOVA and independent samples test analysis, cross-match to transfusion ratio and transfusion possibility, the transfusion index, and maximal surgical blood order schedule were calculated to determine blood transfusion status. RESULTS: Among 872 selected orthopedic surgery candidates, 318 of them were cross-matched and among those, 114 patients received a blood transfusion. In this study, the cross match to transfusion ratio was 6.4, transfusion possibility 36.47%, transfusion index 0.6, and maximal surgical blood order schedule 0.9. CONCLUSION: We found that blood ordering was moderately higher than the standard; so it is highly recommended to focus on the knowledge of evidence based on transfusion and standard guidelines for blood transfusion to avoid over-ordering. PMID- 26894224 TI - A Survey of Blood Request Versus Blood Utilization at a University Hospital in Iran. AB - BACKGROUND: Reservation of blood leads to blood wastage if the blood is not transfused. Therefore, in some centers only blood type and screen are evaluated. In this study, the efficacy of a blood crossmatch-to-transfusion ratio was measured and then compared with the standard levels. METHODS: This prospective study was conducted during one year in a university hospital. During this period, 398 patients for whom blood had been requested were studied. In these patients, at the first surgical type, the laboratory tests (hematocrit, hemoglobin, platelet count, and prothrombin time) and the number of preoperative crossmatched and intraoperative transfused blood units were recorded. Then the crossmatch-to transfusion ratio, transfusion probability, transfusion index, and correlation between related factors, and the transfusion ratio were evaluated. RESULTS: In this cross-sectional study, blood was requested for 398 patients. According to available blood unit deficiency, from 961 blood unit requisitions, only 456 units were crossmatched and 123 units were transfused. The crossmatch-to-transfusion ratio, transfusion probability, and transfusion index were 3.71 (7.81 if all requisitions were crossmatched), 16.83%, and 0.31, respectively. The most unfavorable indexes were observed in patients who had ear, nose, and throat surgeries (0 transfused from 19 crossmatched blood units) and obstetric and gynecologic surgery (crossmatch-to-transfusion ratio was 18.6). The best indexes were related to thoracic surgery and neurosurgery (crossmatch-to-transfusion ratio was 1.53 and 1.54, respectively). There were no significant correlations between hemoglobin, hematocrit, platelet count, and prothrombin time with the number of transfused blood units (P = 0.2, 0.14, 0.26, and 0.06, respectively). CONCLUSION: The data for the crossmatch-to-transfusion ratio, transfusion probability, and transfusion index were suboptimal at this center, especially for ear, nose, and throat and obstetric and gynecologic surgeries. Further multidimensional studies and determination of a new model for blood requests and to decrease blood wastage are needed. PMID- 26894225 TI - Intramuscular Lipoma of the Thenar: A Rare Case. AB - Lipomas are the most common benign mesenchymal tumors. They are located either subcutaneously or under the investing fascia in intramuscular or intermuscular regions. The reported frequency of intramuscular lipomas among all benign adipocytic tumors is 1.0%-5.0% and for intermuscular lipomas is 0.3%-1.9%. The frequency of these lesions is the same in all age groups, but in adults deep seated-lipomas are most commonly discovered between the ages of 30 and 60. The most common sites of involvement of intramuscular lipomas are the large muscles of the extremities, especially those of the thigh, shoulder, and upper arm. Intramuscular lipomas of the hand are extremely rare and only few cases have been reported in the literature. In cases with hand location, they may present with functional deficit or neurovascular compromise due to the effect of the mass. We report an unusual case of a large intramuscular lipoma of the thenar that was treated with surgical excision due to the impairment of hand function. PMID- 26894226 TI - An Isolated Mass in the Palm, Starting Manifestation of Sarcoidosis. AB - Sarcoidosis is a systemic disease that is characterized with noncaseating granulomatous nodules which present in multiple organs specially lungs (90%). Incidence of masses due to Sarcoidosis in upper extremity is low and most cases present in association with involvement of pulmonary hilary lymph nodes. In this article we present a rare case of Sarcoidosis which presented as a single soft tissue mass in hand without osseous or pulmonary hillary lymph node involvement. Incidence of involvement of musculoskeletal system is 1-5 %, mostly it occurs in small bones in hands and feet. In most cases involvement of soft tissue in extremities is accompanied with bone lesions. Those cases of soft tissue involvement are generally coincide with pulmonary lymph nodules. To the authors' knowledge, this is the first case of Sarcoidosis that presents without spreading in bones or pulmonary hilar lymph nodes. PMID- 26894227 TI - Compartment Syndrome of the Calf Due to Nicolau Syndrome. AB - We report a case of Nicolau syndrome in a 15 months old girl following an intramuscular injection of penicillin 6.3.3 in her left buttock. This case is unique because she developed compartment syndrome in her left calf far from her injection site. Her toe's tips gangrened in the course of her ailment. We hypothesized that the compartment syndrome might be produced by a probable intra arterial injection that had produced embolic obstruction of the small and medium size arteries in her leg or a probable perineural or periarteial injection had produced secondary sympathetic stimulation, extensive vasospasm, compromised microcirculation and the development of compartment syndrome. PMID- 26894228 TI - Platelet-Rich Plasma for Frozen Shoulder: A Case Report. AB - Frozen shoulder is a glenohumeral joint disorder that movement because of adhesion and the existence of fibrosis in the shoulder capsule. Platelet-rich plasma can produce collagen and growth factors, which increases stem cells and consequently enhances the healing. To date, there is no evidence regarding the effectiveness of platelet-rich plasma in frozen shoulder. A 45-year-old man with shoulder adhesive capsulitis volunteered for this treatment. He underwent two consecutive platelet-rich plasma injections at the seventh and eighth month after initiation of symptoms. We measured pain, function, ROM by the visual analogue scale (VAS), scores from the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and goniometer; respectively. After first injection, the patient reported 60% improvement regarding diurnal shoulder pain, and no night pain. Also, two-fold improvement for ROM and more than 70% improvement for function were reported. This study suggests the use of platelet-rich plasma in frozen shoulder to be tested in randomized trials. PMID- 26894229 TI - Shiftwork, Sleep Habits, and Metabolic Disparities: Results from the Survey of the Health of Wisconsin. AB - BACKGROUND: With the expanding demand for a 24-hour society, the prevalence of sleep deprivation and other sleep-related health problems is increasing. Shiftwork is an occupational health risk of growing significance because of its high prevalence and because of its potential role as a determinant of socioeconomic-related health disparities. AIMS: The aim of this study was to examine the associations of shiftwork with overweight status and type 2 diabetes, and explore whether a history of sleep problems mediates or modifies these associations. PARTICIPANTS AND METHODS: A cross-sectional study was conducted among 1,593 participants in the Survey of the Health of Wisconsin (2008-12) who were employed and reported work characteristics (traditional schedule or shiftwork) and sleep habits and history of sleep problems (insomnia, insufficient sleep, wake time sleepiness). Objective measures of body mass index (BMI) and type 2 diabetes were used. RESULTS: Shiftworkers were more overweight than traditional-schedule workers (83% vs. 71% with BMI>=25) and reported more sleep problems, such as insomnia symptoms (24% vs. 16%), insufficient sleep (53% vs.43%), and sleepiness (32% vs. 24%). The associations between shiftwork and being overweight or diabetic were stronger among those reporting insufficient sleep, but the interaction was not statistically significant. CONCLUSIONS: Shiftworkers face disparities in metabolic health, particularly those with insufficient sleep. Improved understanding of the relationship between sleep and metabolic states can inform healthcare providers' and employers' efforts to screen high-risk individuals and intervene with workplace wellness initiatives to address these disparities. PMID- 26894230 TI - Prophylactically Decontaminating Human Islet Product for Safe Clinical Application: Effective and Potent Method. AB - BACKGROUND: Transplanting pancreatic islets into recipients must be safe and effective to treat Type 1 diabetes. Islet quality and quantity are important, however, the final product must also be free from microbial contamination and low endotoxin levels. METHODS: This study explored a method to eliminate contamination in manufacturing islets for transplantation. A simple (single antibiotic, n=164) and refined (triple antimicrobial agents, n=279) pancreas decontaminating methods were used to test their effects on reducing the contamination rates in the islet final product. A total of 443 pancreata were processed for islet isolations. Three samples for microbial tests (Gram stain, aerobic, and anaerobic culture) were taken at pre-process (pancreas preservation), post-isolation, and post-culture. Endotoxin levels were measured only for islets considered for transplantation. RESULTS: Out of 443 pancreata used for islet isolation, 79 (17.8%) showed signs of contamination in pre-process samples; 10 (2.3%) were contaminated in both pre-process and in the final product (post-isolation and post-culture) samples. Contamination rates in which pre process and final product samples were positive for contamination was significantly lower using the refined method (refined vs. simple method: 5% vs. 20.5%, p=0.045). Identical microbial species were present in both pre-process and in the final product. CONCLUSIONS: This study demonstrated that the refined method reduces the rate of contamination of the islet final product and is safe for clinical application. Moreover, it may be used as a standard method during human islet manufacturing facilitating the application of a biological license agreement from United States Food and Drug Administration. PMID- 26894231 TI - microRNAs as Biomarker in Depression Pathogenesis. AB - Major depressive disorder (MDD) is a major health concern with alarming rates of completed suicide. Thus, it is important to understand the pathophysiology of this disorder. In addition, disturbingly high rates of relapse and low rates of recovery make it urgent not only to develop targeted treatments but to identify biomarkers that can predict treatment response for individual patients. MicroRNAs (miRNAs) are a class of small non-coding RNAs that control gene expression by modulating translation, mRNA degradation or stability of mRNA targets. The role of miRNAs in disease pathophysiology is emerging rapidly. Several recent studies have suggested the possible role of miRNAs in synaptic plasticity, neurogenesis, and stress response, all implicated in MDD. Emerging studies showthe direct role of miRNAs in the development of depression phenotype. More recently, the role of miRNAs in prognosis and treatment response is being considered for various disease pathophysiology, including MDD. The review discusses the recent studies demonstrating the role of miRNAs in MDD and whether miRNA can be used as a biomarker for MDD pathogenesis and treatment response. PMID- 26894233 TI - Barriers and Negative Nudges: Exploring Challenges in Food Journaling. AB - Although food journaling is understood to be both important and difficult, little work has empirically documented the specific challenges people experience with food journals. We identify key challenges in a qualitative study combining a survey of 141 current and lapsed food journalers with analysis of 5,526 posts in community forums for three mobile food journals. Analyzing themes in this data, we find and discuss barriers to reliable food entry, negative nudges caused by current techniques, and challenges with social features. Our results motivate research exploring a wider range of approaches to food journal design and technology. PMID- 26894232 TI - Analysis of miRNA in Normal Appearing White Matter to Identify Altered CNS Pathways in Multiple Sclerosis. AB - Genetic studies suggest that the immune system is the greatest genetic contributor to multiple sclerosis (MS) susceptibility. Yet, these immune-related genes do not explain why inflammation is limited to the CNS in MS. We hypothesize that there is an underlying dysregulation in the CNS of MS patients that makes them more vulnerable to CNS inflammation. The sparsity of CNS-related genes associated with MS suggests that epigenetic changes in the CNS may play a role. Thus, a miRNA profiling study was performed in NAWM of MS patients and control subjects to determine if specific CNS pathways can be identified that may be altered due to miRNA-mediated post-transcriptional dysregulation. There were 15 differentially expressed miRNAs found in the MS patients' NAWM. Pathway analysis indicated that the MAPK pathway and pathways associated with the blood-brain barrier were predicted to be significantly affected by these miRNAs. Using target predication and mRNA analysis, an inverse relationship was found between miR-191 and BDNF, SOX4, FZD5 and WSB1. The pathway and target analysis of the MS associated miRNAs suggests that MS patients' CNS is more prone to inflammation and less capable of repair, yet enriched in neuroprotective mechanisms. PMID- 26894234 TI - Stress granules (SG) and processing bodies (PB) in viral infections. AB - During reaction to stress caused by viral infection, RNA granules are formed in order to protect mRNA. Stress granules (SG) and processing bodies (PB) provide cell homeostasis and mRNA stability. They are formed, for example, during polio virus and MRV (mammalian orthoreovirus) infections. Some viruses, such as influenza virus and HTLV-1 (Human T-lymphotropic virus 1), block the formation of granules. In addition, there are viruses like West Nile Virus, Hepatitis C Virus (HCV) or human Herpes viruses, which influence the functioning of the granules. PMID- 26894237 TI - Quantum Entanglement and Chemical Reactivity. AB - The water molecule and a hydrogenic abstraction reaction are used to explore in detail some quantum entanglement features of chemical interest. We illustrate that the energetic and quantum-information approaches are necessary for a full understanding of both the geometry of the quantum probability density of molecular systems and the evolution of a chemical reaction. The energy and entanglement hypersurfaces and contour maps of these two models show different phenomena. The energy ones reveal the well-known stable geometry of the models, whereas the entanglement ones grasp the chemical capability to transform from one state system to a new one. In the water molecule the chemical reactivity is witnessed through quantum entanglement as a local minimum indicating the bond cleavage in the dissociation process of the molecule. Finally, quantum entanglement is also useful as a chemical reactivity descriptor by detecting the transition state along the intrinsic reaction path in the hypersurface of the hydrogenic abstraction reaction corresponding to a maximally entangled state. PMID- 26894240 TI - Stochastic Multiconfigurational Self-Consistent Field Theory. AB - The multiconfigurational self-consistent field theory is considered the standard starting point for almost all multireference approaches required for strongly correlated molecular problems. The limitation of the approach is generally given by the number of strongly correlated orbitals in the molecule, since its cost will grow exponentially with this number. We present a new multiconfigurational self-consistent field approach, wherein linear determinant coefficients of a multiconfigurational wave function are optimized via the stochastic full configuration interaction quantum Monte Carlo technique at greatly reduced computational cost, with nonlinear orbital rotation parameters updated variationally based on this sampled wave function. This extends this approach to strongly correlated systems with far larger active spaces than it is possible to treat via conventional means. By comparison with this traditional approach, we demonstrate that the introduction of stochastic noise in both the determinant amplitudes and the gradient and Hessian of the orbital rotations does not preclude robust and reliable convergence of the orbital optimization. It can even improve the ability to avoid convergence to local minima in the orbital space, and therefore aid in finding variationally lower-energy solutions. We consider the effect on the convergence of the orbitals as the number of walkers and the sampling time within the active space increases, as well as the effect on the final energy and error. The scope of the new protocol is demonstrated with a study of the increasingly strongly correlated electronic structure in a series of polycyclic aromatic hydrocarbons, up to the large coronene molecule in a complete active space of 24 pi electrons in 24 orbitals, requiring only modest computational resources PMID- 26894242 TI - Long-Range Corrected DFT Meets GW: Vibrationally Resolved Photoelectron Spectra from First Principles. AB - We propose an entirely nonempirical and computationally efficient scheme to calculate highly reliable vibrationally resolved photoelectron spectra for molecules from first principles. To this end, we combine nonempirically tuned long-range corrected hybrid functionals with non-self-consistent many-body perturbation theory in the G0W0 approximation and a Franck-Condon multimode analysis based on DFT-calculated frequencies. The vibrational analysis allows for a direct comparison of the GW-calculated spectra to gas-phase ultraviolet photoelectron measurements of neutral and anionic molecules, respectively. Direct comparison of the calculated peak maxima with experiment yields mean absolute errors below 0.1 eV for ionization potentials, electron affinities, and fundamental gaps, clearly outperforming commonly used G0W0 approaches at similar numerical costs. PMID- 26894243 TI - Large-Scale Quantitative Assessment of Binding Preferences in Protein-Nucleic Acid Complexes. AB - The growing number of high-quality experimental (X-ray, NMR) structures of protein-DNA complexes has sufficient enough information to assess whether universal rules governing the DNA sequence recognition process apply. While previous studies have investigated the relative abundance of various modes of amino acid-base contacts (van der Waals contacts, hydrogen bonds), relatively little is known about the energetics of these noncovalent interactions. In the present study, we have performed the first large-scale quantitative assessment of binding preferences in protein-DNA complexes by calculating the interaction energies in all 80 possible amino acid-DNA base combinations. We found that several mutual amino acid-base orientations featuring bidentate hydrogen bonds capable of unambiguous one-to-one recognition correspond to unique minima in the potential energy space of the amino acid-base pairs. A clustering algorithm revealed that these contacts form a spatially well-defined group offering relatively little conformational freedom. Various molecular mechanics force field and DFT-D ab initio calculations were performed, yielding similar results. PMID- 26894239 TI - Critical Analysis of Cluster Models and Exchange-Correlation Functionals for Calculating Magnetic Shielding in Molecular Solids. AB - Calculations of the principal components of magnetic-shielding tensors in crystalline solids require the inclusion of the effects of lattice structure on the local electronic environment to obtain significant agreement with experimental NMR measurements. We assess periodic (GIPAW) and GIAO/symmetry adapted cluster (SAC) models for computing magnetic-shielding tensors by calculations on a test set containing 72 insulating molecular solids, with a total of 393 principal components of chemical-shift tensors from 13C, 15N, 19F, and 31P sites. When clusters are carefully designed to represent the local solid state environment and when periodic calculations include sufficient variability, both methods predict magnetic-shielding tensors that agree well with experimental chemical-shift values, demonstrating the correspondence of the two computational techniques. At the basis-set limit, we find that the small differences in the computed values have no statistical significance for three of the four nuclides considered. Subsequently, we explore the effects of additional DFT methods available only with the GIAO/cluster approach, particularly the use of hybrid-GGA functionals, meta-GGA functionals, and hybrid meta-GGA functionals that demonstrate improved agreement in calculations on symmetry-adapted clusters. We demonstrate that meta-GGA functionals improve computed NMR parameters over those obtained by GGA functionals in all cases, and that hybrid functionals improve computed results over the respective pure DFT functional for all nuclides except 15N. PMID- 26894238 TI - Efficient Algorithms for Estimating the Absorption Spectrum within Linear Response TDDFT. AB - We present a special symmetric Lanczos algorithm and a kernel polynomial method (KPM) for approximating the absorption spectrum of molecules within the linear response time-dependent density functional theory (TDDFT) framework in the product form. In contrast to existing algorithms, the new algorithms are based on reformulating the original non-Hermitian eigenvalue problem as a product eigenvalue problem and the observation that the product eigenvalue problem is self-adjoint with respect to an appropriately chosen inner product. This allows a simple symmetric Lanczos algorithm to be used to compute the desired absorption spectrum. The use of a symmetric Lanczos algorithm only requires half of the memory compared with the nonsymmetric variant of the Lanczos algorithm. The symmetric Lanczos algorithm is also numerically more stable than the nonsymmetric version. The KPM algorithm is also presented as a low-memory alternative to the Lanczos approach, but the algorithm may require more matrix-vector multiplications in practice. We discuss the pros and cons of these methods in terms of their accuracy as well as their computational and storage cost. Applications to a set of small and medium-sized molecules are also presented. PMID- 26894235 TI - Halophilic microorganisms in deteriorated historic buildings: insights into their characteristics. AB - Historic buildings are constantly being exposed to numerous climatic changes such as damp and rainwater. Water migration into and out of the material's pores can lead to salt precipitation and the so-called efflorescence. The structure of the material may be seriously threatened by salt crystallization. A huge pressure is produced when salt hydrates occupy larger spaces, which leads at the end to cracking, detachment and material loss. Halophilic microorganisms have the ability to adapt to high salinity because of the mechanisms of inorganic salt (KCl or NaCl) accumulation in their cells at concentrations isotonic to the environment, or compatible solutes uptake or synthesis. In this study, we focused our attention on the determination of optimal growth conditions of halophilic microorganisms isolated from historical buildings in terms of salinity, pH and temperature ranges, as well as biochemical properties and antagonistic abilities. Halophilic microorganisms studied in this paper could be categorized as a halotolerant group, as they grow in the absence of NaCl, as well as tolerate higher salt concentrations (Staphylococcus succinus, Virgibacillus halodenitrificans). Halophilic microorganisms have been also observed (Halobacillus styriensis, H. hunanensis, H. naozhouensis, H. litoralis, Marinococcus halophilus and yeast Sterigmatomyces halophilus). With respect to their physiological characteristics, cultivation at a temperature of 25-30 degrees C, pH 6-7, NaCl concentration for halotolerant and halophilic microorganisms, 0-10% and 15-30%, respectively, provides the most convenient conditions. Halophiles described in this study displayed lipolytic, glycolytic and proteolytic activities. Staphylococcus succinus and Marinococcus halophilus showed strong antagonistic potential towards bacteria from the Bacillus genus, while Halobacillus litoralis displayed an inhibiting ability against other halophiles. PMID- 26894241 TI - What Exactly Is the Light Emitter of a Firefly? AB - Firefly bioluminescence attracts people by its glaring beauty and fascinating applications, but what is the light emitter of a firefly? The answer to this question has been explored since before the 1960s. The unanimously accepted answer is that excited-state oxyluciferin is the light emitter. The complexity of this question arises from the existence of six chemical forms (keto, enol, keto 1, enol-1, enol-1', and enol-2) of oxyluciferin. After decades of experimental and theoretical efforts, a consistent conclusion was almost reached in 2011: excited-state keto-1 is the only light emitter in fireflies. However, the debate is raised again by the latest in vitro experimental results. This study will solve this contradiction via hybrid quantum mechanics and molecular mechanics (QM/MM) calculations combined with molecular dynamics (MD). The calculations were performed in the real protein for the six chemical forms of oxyluciferin and their corresponding analogues employed in the latest experiments. By considering the real environment, the pH value, and a possible equilibrium of the chemical forms of oxyluciferin in vivo, the calculated results indicate that the main emitter is still the excited-state keto-1 form. PMID- 26894236 TI - Environmental parameters conditioning microbially induced mineralization under the experimental model conditions. AB - Microbially induced calcium carbonate precipitation is one of the biomineralization types closely dependent on the parameters of the microenvironment. Minerals are precipitated as a product of environmental and bacterial cell interactions, however, this system has very little control via microorganisms. The aim of research was to determine the influence of abiotic factors (pH, temperature, agitation speed of bacterial culture and calcium ion source) on the mineralization induced by Arthrobacter sulfureus, Bacillus muralis and B. atrophaeus strains under the standard laboratory conditions. Because of the key role of urease in biomineralization, processes occurring in environments with and without the urea were compared. For this purpose, cultivation of bacteria (A. sulfureus, B. muralis and B. atrophaeus) was carried out in B4 liquid medium for 5 days with various environmental parameters (pH 6-9; temperature 25-44 degrees C; speed of agitation 0-180 rpm, different calcium sources). It was noticed that the pH and the speed of agitation clearly affect the amount of the calcium carbonate that formed. Our observations suggest that the highest precipitation rate takes place in alkaline pH between 8-9, with shaking at 180 rpms. Among studied sources of calcium ions (calcium acetate, calcium chloride and calcium nitrate), calcium acetate demonstrated the strongest potential in the biomineralization process. Moreover, work presented here demonstrates that the correlation between cultivation temperature and biomineralization process cannot be clearly evaluated. The morphology and size of calcium carbonate minerals was strain-specific, although affected by the presence of urea in the surrounding solution. PMID- 26894244 TI - Demographics, training satisfaction, and career plans of Canadian oral and maxillofacial surgery residents. AB - The purpose of this study was to evaluate the demographics, training satisfaction, and career plans of Canadian oral and maxillofacial surgery (OMS) residents. A cross-sectional study was conducted using an anonymous online survey that was distributed via e-mail to all current Canadian OMS residents. The completion rate of this survey was 88.9%. Eighty percent of residents were satisfied with their surgical education overall. Residents were most satisfied with their training in the areas of facial trauma and orthognathic surgery. Satisfaction was lowest in the areas of facial cosmetic surgery, maxillofacial reconstructive surgery, cleft and craniofacial surgery, and dental implantology. A majority of residents, 78.1%, indicated that they would prefer to be trained in an MD-integrated OMS certificate program. Seventy-two percent of residents indicated that they would like to complete a fellowship following graduation. The most desirable career path was a combination of private practice and academic practice, with 75.0% of residents selecting this option. Overall, Canadian OMS residents were pleased with their training in the traditional scope of OMS, apart from dental implantology. Among the current generation of trainees, there appears to be a proclivity for a broader scope of practice, dual-degree training, and post-graduate fellowship training. PMID- 26894245 TI - Idarucizumab, a Humanized, Monoclonal Antibody Fragment for Immediate Reversal of Dabigatran. AB - OBJECTIVE: To evaluate the role of idarucizumab, a humanized monoclonal antibody fragment, as a specific reversal agent for the anticoagulant activity of dabigatran and to review the pharmacology, pharmacokinetic properties, efficacy, and safety of this agent. METHODS: A literature search was conducted consisting of a PubMed database using the MeSH term idarucizumab and the key word dabigatran antidote. Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of idarucizumab for the reversal of the anticoagulant activity of dabigatran were included. RESULTS: Idarucizumab represents a novel treatment option as it is the only humanized, monoclonal antibody fragment that specifically binds to dabigatran. Studies evaluating reversal of dabigatran induced anticoagulation have demonstrated immediate, complete, and sustained effects with idarucizumab. Idarucizumab did not overcorrect thrombin generation. Additionally, evaluations have shown that dabigatran can be safely reinitiated 24 hours after the administration of idarucizumab. The United States Food and Drug Administration granted priority review for the biologic license application and accelerated approval for idarucizumab. CONCLUSION: Idarucizumab represents an encouraging development in the reversal of dabigatran. Its novel mechanism of action, pharmacokinetics, tolerability, and lack of thrombotic events contribute positively to its use in patients who experience bleeding or for those who require emergent surgery or procedures. PMID- 26894246 TI - [Not Available]. PMID- 26894247 TI - [Not Available]. PMID- 26894248 TI - Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. PMID- 26894250 TI - Geoscience: Ups and downs. PMID- 26894249 TI - Chris Marshall (1949-2015)--a personal reflection and tribute. PMID- 26894251 TI - Ronald M. Burde (1938-2015). PMID- 26894252 TI - Electronic Properties of Zigzag Graphene Nanoribbons Studied by TAO-DFT. AB - Accurate prediction of the electronic properties of zigzag graphene nanoribbons (ZGNRs) has been very challenging for conventional electronic structure methods due to the presence of strong static correlation effects. To meet the challenge, we study the singlet-triplet energy gaps, vertical ionization potentials, vertical electron affinities, fundamental gaps, and symmetrized von Neumann entropy (i.e., a measure of polyradical character) of hydrogen-terminated ZGNRs with different widths and lengths using our recently developed thermally assistedoccupation density functional theory (TAO-DFT) [Chai, J.-D. J. Chem. Phys. 2012, 136, 154104], a very efficient method for the study of large strongly correlated systems. Our results are in good agreement with the available experimental and high-accuracy ab initio data. The ground states of ZGNRs are shown to be singlets for all the widths and lengths investigated. With the increase of ribbon length, the singlet-triplet energy gaps, vertical ionization potentials, and fundamental gaps decrease monotonically, while the vertical electron affinities and symmetrized von Neumann entropy increase monotonically. On the basis of the calculated orbitals and their occupation numbers, the longer ZGNRs are shown to possess increasing polyradical character in their ground states, where the active orbitals are mainly localized at the zigzag edges. PMID- 26894253 TI - Computational Benchmarking for Ultrafast Electron Dynamics: Wave Function Methods vs Density Functional Theory. AB - Attosecond electron dynamics in small- and medium-sized molecules, induced by an ultrashort strong optical pulse, is studied computationally for a frozen nuclear geometry. The importance of exchange and correlation effects on the nonequilibrium electron dynamics induced by the interaction of the molecule with the strong optical pulse is analyzed by comparing the solution of the time dependent Schrodinger equation based on the correlated field-free stationary electronic states computed with the equationof-motion coupled cluster singles and doubles and the complete active space multi-configurational self-consistent field methodologies on one hand, and various functionals in real-time time-dependent density functional theory (TDDFT) on the other. We aim to evaluate the performance of the latter approach, which is very widely used for nonlinear absorption processes and whose computational cost has a more favorable scaling with the system size. We focus on LiH as a toy model for a nontrivial molecule and show that our conclusions carry over to larger molecules, exemplified by ABCU (C10H19N). The molecules are probed with IR and UV pulses whose intensities are not strong enough to significantly ionize the system. By comparing the evolution of the time-dependent field-free electronic dipole moment, as well as its Fourier power spectrum, we show that TD-DFT performs qualitatively well in most cases. Contrary to previous studies, we find almost no changes in the TD-DFT excitation energies when excited states are populated. Transitions between states of different symmetries are induced using pulses polarized in different directions. We observe that the performance of TD-DFT does not depend on the symmetry of the states involved in the transition. PMID- 26894254 TI - Biological Warfare Plan in the 17th Century-the Siege of Candia, 1648-1669. AB - A little-known effort to conduct biological warfare occurred during the 17th century. The incident transpired during the Venetian-Ottoman War, when the city of Candia (now Heraklion, Greece) was under siege by the Ottomans (1648-1669). The data we describe, obtained from the Archives of the Venetian State, are related to an operation organized by the Venetian Intelligence Services, which aimed at lifting the siege by infecting the Ottoman soldiers with plague by attacking them with a liquid made from the spleens and buboes of plague victims. Although the plan was perfectly organized, and the deadly mixture was ready to use, the attack was ultimately never carried out. The conception and the detailed cynical planning of the attack on Candia illustrate a dangerous way of thinking about the use of biological weapons and the absence of reservations when potential users, within their religious framework, cast their enemies as undeserving of humanitarian consideration. PMID- 26894255 TI - Self-Assembly of 4-(Diethylboryl)pyridine: Crystal Structures of the Cyclic Pentamer and Hexamer and Their Solvent-Dependent Selective Crystallization. AB - Two distinct oligomeric structures were obtained by the self-assembly of 4 (diethylboryl)pyridine (1). In the (1)H NMR spectrum of 1 in CDCl3, at least two sets of signals were observed for the pyridyl alpha- and beta-hydrogen atoms. ESI MS, VPO, and TLC analysis revealed that 1 assembles mainly into a mixture of cyclic pentamers and hexamers in solution via intermolecular boron-nitrogen coordination bonds. Crystallization of 1 in THF by vapor diffusion of EtOH or in CHCl3 afforded the cyclic hexamer incorporating one THF molecule (16.THF) or 1.5 mol equiv of chloroform molecule (16.CHCl3), respectively. Similarly, a solution of 1 in a mixture of benzene and hexane furnished the cyclic pentamer bearing two benzene molecules (15.C6H6). It seems that the solvent differences affected the crystallization of the two distinct cyclic oligomers of 1, either of which was cocrystallized predominantly with the solvent molecule. Thermogravimetric analysis of the crystals and NMR studies of the solution revealed that the noncovalent interactions between the host and guest are not strong enough to hold the guest molecule in the cavity. PMID- 26894257 TI - What factors mediate the relationship between global self-worth and weight and shape concerns? AB - The primary aim of this study was to investigate whether the relationship between global self-worth and weight concerns and global self-worth and shape concerns was mediated by pertinent body image factors, while controlling for gender and estimated BMI. Participants were 775 adolescents (56% male) aged 12-18years (M=14.6; SD=1.50). Mediation analysis revealed a direct and a mediated effect between global self-worth and two body image models: 1) weight concerns and 2) shape concerns. The strongest mediators in both models were physical appearance, restrained eating, and depression. Partial mediation was observed for both models, indicating that body image factors which span cognitive, affective, and behavioral constructs, explain the association between global self-worth and weight and shape concerns. Implications for future research, weight and shape concern prevention and global self-worth enhancement programs are discussed. PMID- 26894258 TI - In Situ Monitoring and Mechanism of the Mechanochemical Formation of a Microporous MOF-74 Framework. AB - Mechanochemistry provides a rapid, efficient route to metal-organic framework Zn MOF-74 directly from a metal oxide and without bulk solvent. In situ synchrotron X-ray diffraction monitoring of the reaction course reveals two new phases and an unusual stepwise process in which a close-packed intermediate reacts to form the open framework. The reaction can be performed on a gram scale to yield a highly porous material after activation. PMID- 26894256 TI - Highly accelerated cardiac MRI using iterative SENSE reconstruction: initial clinical experience. AB - To evaluate the qualitative and quantitative performance of an accelerated cardiovascular MRI (CMR) protocol that features iterative SENSE reconstruction and spatio-temporal L1-regularization (IS SENSE). Twenty consecutively recruited patients and 9 healthy volunteers were included. 2D steady state free precession cine images including 3-chamber, 4-chamber, and short axis slices were acquired using standard parallel imaging (GRAPPA, acceleration factor = 2), spatio temporal undersampled TSENSE (acceleration factor = 4), and IS SENSE techniques (acceleration factor = 4). Acquisition times, quantitative cardiac functional parameters, wall motion abnormalities (WMA), and qualitative performance (scale: 1-poor to 5-excellent for overall image quality, noise, and artifact) were compared. Breath-hold times for IS SENSE (3.0 +/- 0.6 s) and TSENSE (3.3 +/- 0.6) were both reduced relative to GRAPPA (8.4 +/- 1.7 s, p < 0.001). No difference in quantitative cardiac function was present between the three techniques (p = 0.89 for ejection fraction). GRAPPA and IS SENSE had similar image quality (4.7 +/- 0.4 vs. 4.5 +/- 0.6, p = 0.09) while, both techniques were superior to TSENSE (quality: 4.1 +/- 0.7, p < 0.001). GRAPPA WMA agreement with IS SENSE was good (kappa > 0.60, p < 0.001), while agreement with TSENSE was poor (kappa < 0.40, p < 0.001). IS SENSE is a viable clinical CMR acceleration approach to reduce acquisition times while maintaining satisfactory qualitative and quantitative performance. PMID- 26894260 TI - Entrapment of Water at the Transmembrane Helix-Helix Interface of Quiescin Sulfhydryl Oxidase 2. AB - Little is known about how a membrane can regulate interactions between transmembrane helices. Here, we show that strong self-interaction of the transmembrane helix of human quiescin sulfhydryl oxidase 2 rests on a motif of conserved amino acids comprising one face of the helix. Atomistic molecular dynamics simulations suggest that water molecules enter the helix-helix interface and connect serine residues of both partner helices. In addition, an interfacial tyrosine can interact with noninterfacial water or lipid. Dimerization of this transmembrane helix might therefore be controlled by membrane properties controlling water permeation and/or by the lipid composition of the membrane. PMID- 26894261 TI - Corrigendum. PMID- 26894259 TI - Cognition and Indicators of Dietary Habits in Older Adults from Southern Brazil. AB - OBJECTIVE: To assess the association between unhealthy dietary habits and cognition in older adults from Southern Brazil. METHODS: This cross-sectional study analyzed data from the second wave of a population- and household-based epidemiological survey (2013-2014) conducted in the city of Florianopolis. A total of 1,197 older adults (778 women) over 60 years old participated in the study. Cognition, the dependent variable, was measured by the Mini-Mental State Examination (MMSE). The independent variables were the following indicators of unhealthy dietary habits: low intake of fruits and vegetables (<= 4 servings/day); fish (< 1 serving/week); and habitual fatty meat intake (yes/no). Adjustments were made for age, education level, income, smoking status, alcohol intake, leisure-time physical activity, depression symptoms, chronic diseases, and body mass index. Simple and multiple linear regression analyses were performed, considering sampling weights and stratification by gender. RESULTS: The mean MMSE scores for men and women were 25.15 +/- 5.56 and 24.26 +/- 5.68, respectively (p = 0.009). After adjustments, in women low fruit and vegetable intake (<= 4 servings/day) was independently associated with the lowest MMSE scores. No associations were found in men. Additionally, women's mean MMSE scores increased as their daily frequency of fruit and vegetable intake increased (p = 0.001). CONCLUSION: Women with low fruit and vegetable intake according to the World Health Organization (WHO) have lower cognition scores. Regular intake of fruits, vegetables, and fish in exchange of fatty meats may be a viable public policy strategy to preserve cognition in aging. PMID- 26894262 TI - Controlled Folding, Motional, and Constitutional Dynamic Processes of Polyheterocyclic Molecular Strands. AB - General design principles have been developed for the control of the structural features of polyheterocyclic strands and their effector-modulated shape changes. Induced defined molecular motions permit designed enforcement of helical as well as linear molecular shapes. The ability of such molecular strands to bind metal cations allows the generation of coiling/uncoiling processes between helically folded and extended linear states. Large molecular motions are produced on coordination of metal ions, which may be made reversible by competition with an ancillary complexing agent and fueled by sequential acid/base neutralization energy. The introduction of hydrazone units into the strands confers upon them constitutional dynamics, whereby interconversion between different strand compositions is achieved through component exchange. These features have relevance for nanomechanical devices. We present a morphological and functional analysis of such systems developed in our laboratories. PMID- 26894263 TI - Asymptomatic atrial fibrillation burden and thromboembolic events: piecing evidence together. AB - BACKGROUND: Contributory evidence on a direct association between asymptomatic atrial fibrillation (AF) burden and thromboembolic events is conflicting and contradictory. The aim of the article is to gather evidence available for a direct correlation between burden and stroke. METHODS: A literature search was performed to capture studies reporting data on the impact of asymptomatic AF burden on the risk of stroke. Data was then extracted from each included study including burden of AF, hazard ratio (HR) for stroke, and CHADS2 score. A random effects meta-analysis was carried out on the log-transformed HRs for different subgroups of AF burden. A meta-regression was performed on the two variables: burden of asymptomatic AF and CHADS2 score. RESULTS: The random-effect pooled analysis performed on a single subgroup of the six studies reporting data on HR, showed a HR of 2.150 (95% CI 1.523-3.003) for stroke during asymptomatic AF compared to sinus rhythm. At univariate meta-regression, no correlation was detected between burden of asymptomatic AF and HR for stroke (p-value 0,874). When CHADS2 score was included in the regression model as a covariate, no significant association was detected (p-value 0,939). CONCLUSION: A direct correlation between burden of asymptomatic AF and HR for stroke cannot be detected in our pooled analysis. However, due to the limitations acknowledged in the analysis, our findings need to be confirmed in large cohort studies. PMID- 26894265 TI - Erratum to: The Clinical Utility of TIMP3 Expression in ACTH-Secreting Pituitary Tumor. PMID- 26894264 TI - Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats. AB - The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Calpha and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, Gabrb3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABAA (beta-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABAA (beta-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABAA (beta-1) receptor and CREB1 in the NAc, probably via activating PKA signalling. PMID- 26894266 TI - Diabetes in Thailand: Status and Policy. AB - Like other countries in the Western Pacific region, Thailand is facing increasing numbers of patients with diabetes due to unhealthy diets, high obesity rates, and an aging society. Diabetes is a considerable burden for developing countries as it reduces quality of life, increases mortality, and drives up healthcare costs. The disease detection rate in Thailand has improved in recent years, but glycemic control remains suboptimal and significant numbers of patients suffer from complications. Universal healthcare coverage has increased access to care, but inequality exists between different health plans and non-medication diabetes supplies are not yet widely covered. Diabetes self-management education has not yet been standardized and a multidisciplinary team approach is not widely utilized. The Thai government recognizes the burden of diabetes and has launched nationwide programs of health promotion and disease prevention. In addition, local initiatives have targeted reductions in specific complications, including retinopathy and diabetic foot problems, which has resulted in better disease prevention and treatment. Along with strategic public health planning, increased collaboration between private and public sectors, enhanced professional training, increased use of technology and data management, and equitable distribution of care are all needed to improve outcomes of patients with diabetes in Thailand. PMID- 26894268 TI - Tumor Suppressor in Lung Cancer-1 Is a Prognostic Predictor for the Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer. AB - OBJECTIVE: To investigate the relationship between the expression of tumor suppressor in lung cancer-1 (TSLC1) and clinicopathological characteristics of patients with non-muscle-invasive bladder cancer (NMIBC) and evaluate the prognostic significance of TSLC1. METHODS: TSLC1 expression in 241 specimens of NMIBC was examined by immunohistochemistry. The correlation between TSLC1 expression and clinicopathological characteristics was evaluated using the chi square test. The prognostic significance of TSLC1 was analyzed by univariate, multivariate analysis and Kaplan-Meier survival curves. RESULTS: The total negative rate of TSLC1 expression was 47.3% in NMIBC. Decreased expression of TSLC1 was correlated with a higher clinical stage, higher pathological grade, the number of tumors, lager tumor size, tumor recurrence and progression. TSLC1 expression was an independent risk factor for predicting tumor recurrence (p = 0.005) and progression (p < 0.001). CONCLUSION: Decreased expression of TSLC1 is correlated with the malignancy of NMIBC tissues and low TSLC1 expression may serve as a predictor for bladder cancer recurrence and progression. PMID- 26894267 TI - Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue engineering for spinal cord defect repair in rat fetuses with spina bifida aperta. AB - Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta. Scaffold characterisation revealed the porous structure, organic and amorphous content. This biomaterial promoted the adhesion, spreading and in vitro viability of the BMSCs. After transplantation of the scaffold combined with BMSCs, the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously under stereomicroscopy, and the skin defect almost closed in many fetuses. The transplanted BMSCs in chitosan-gelatin scaffold survived, grew and expressed markers of neural stem cells and neurons in the defective spinal cord. In addition, the biomaterial presented high biocompatibility and slow biodegradation in vivo. In conclusion, prenatal transplantation of the scaffold combined with BMSCs could treat spinal cord defect in fetuses with spina bifida aperta by the regeneration of neurons and repairmen of defective region. PMID- 26894270 TI - Uptake of Cervical Cancer Screening and Associated Factors among Women in Rural Uganda: A Cross Sectional Study. AB - BACKGROUND: In developing countries, inadequate access to effective screening for cervical cancer often contributes to the high morbidity and mortality caused by the disease. The largest burden of this falls mostly on underserved populations in rural areas, where health care access is characterized by transport challenges, ill equipped health facilities, and lack of information access. This study assessed uptake of cervical cancer screening and associated factors among women in rural Uganda. METHODS: This descriptive cross sectional study was carried out in Bugiri and Mayuge districts in eastern Uganda and utilised quantitative data collection methods. Data were collected using a semi-structured questionnaire on cervical cancer screening among females aged between 25 and 49 years who had spent six or more months in the area. Data were entered in Epidata 3.02 and analysed in STATA 12.0 statistical software. Univariate, bivariate and multivariate analyses were performed. RESULTS: Of the 900 women, only 43 (4.8%) had ever been screened for cervical cancer. Among respondents who were screened, 21 (48.8%) did so because they had been requested by a health worker, 17 (39.5%) had certain signs and symptoms they associated with cervical cancer while 16 (37.2%) did it voluntarily to know their status. Barriers to cervical cancer screening were negative individual perceptions 553 (64.5%) and health facility related challenges 142 (16.6%). Other respondents said they were not aware of the screening service 416 (48.5%). The independent predictors of cervical cancer screening were: being recommended by a health worker [AOR = 87.85, p<0.001], knowing where screening services were offered [AOR = 6.24, p = 0.004], and knowing someone who had ever been screened [AOR = 9.48, p = 0.001]. CONCLUSION: The prevalence of cervical cancer screening is very low in rural Uganda. Interventions to increase uptake of cervical cancer screening should be implemented so as to improve access to the service in rural areas. PMID- 26894269 TI - The psychosocial experience of individuals living with osteogenesis imperfecta: a mixed-methods systematic review. AB - PURPOSE: Osteogenesis imperfecta (OI) is a genetic disorder (prevalence: 1:10,000), leading to bone fragility, frequent fractures, and varying degrees of physical limitations. Despite a substantial amount of research on the genetics, pathophysiology, and treatments related to OI, there remains a paucity of knowledge concerning the lived psychosocial experience of the OI population. This mixed-methods systematic review aimed to review, appraise, and synthesize the literature on the psychosocial experience of children and adults with OI with the goal of identifying implications for research, practice, and policy-making. METHODS: Using a systematic methodology, quantitative, qualitative, and mixed methods studies were accessed through database searching, screened, assessed for eligibility, and appraised. Data from the selected studies fulfilling the eligibility and quality criteria were extracted and synthesized using thematic analysis with an inductive approach. RESULTS: A total of four qualitative and 20 quantitative studies, with various study designs and methodologies ranging in quality, were included in the review (n = 800; comprising 610 children and 175 adults with OI types I, III, IV, and V, ten parents and five healthcare professionals). Six themes were identified: intellectual feats, isolation and feeling different, fear of fractures, coping with challenges, adapting by learning new skills, and social relationships. CONCLUSION: These findings highlighted key aspects of the experiences of children and adults with OI and will be essential for improving the quality and direction of research, tailoring clinical interventions addressing the psychosocial needs and quality of life of individuals with OI, and raising awareness among caregivers, healthcare professionals, administrators, and policy-makers associated with the OI population. PMID- 26894272 TI - New Family of Octagonal-Prismatic Lanthanide Coordination Cages Assembled from Unique Ln17 Clusters and Simple Cliplike Dicarboxylate Ligands. AB - Novel high-nuclearity lanthanide clusters (Ln17) are generated in situ in the coordination-driven self-assembly. A metal-cluster-directed symmetry strategy for building metal coordination cages is successfully applied to a lanthanide system for the first time. A new family of octagonal-prismatic lanthanide coordination cages UJN-Ln, formulated as [Ln(MU3-OH)8][Ln16(MU4-O)(MU4-OH)(MU3-OH)8(H2O)8(MU4 dcd)8][(MU3-dcd)8].22H2O (Ln = Gd, Tb, Dy, Ho, and Er; dcd = 3,3 dimethylcyclopropane-1,2-dicarboxylate dianion), have been assembled from the unique Ln17 clusters and simple cliplike ligand H2dcd. Apart from featuring aesthetically charming structures, all of the compounds present predominantly antiferromagnetic coupling between the corresponding lanthanide ions. Additionally, the intense-green photoluminescence for UJN-Tb and magnetic relaxation behavior for UJN-Dy have been observed. Remarkably, UJN-Gd shows a large magnetocaloric effect (MCE) with an impressive entropy change value of 42.3 J kg(-1) K(-1) for DeltaH = 7.0 T at 2.0 K due to the high-nuclearity cluster and the lightweight ligand. The studies highlight the structural diversity of multigonal-prismatic metal coordination cages and provide a new direction in the design of cagelike multifunctional materials by the introduction of lanthanide clusters and other suitable cliplike ligands. PMID- 26894271 TI - Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney. AB - The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 +/- 87.4, 754.31 +/- 77.09 and 206.1 +/- 16.89 mm3, respectively. The glomerular number was 32844.03 +/- 1069.19, and the total glomerular volume was estimated to be 36.7 +/- 1.45 mm3. The volume and length of the proximal convoluted tubule were estimated at 585.67 +/- 60.7 mm3 and 328.8 +/- 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 +/- 7.38 mm3 and 234.4 +/- 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel. PMID- 26894273 TI - Appropriateness, Reasons and Independent Predictors of Consultations in the Emergency Department (ED) of a Dutch Tertiary Care Center: A Prospective Cohort Study. AB - OBJECTIVE: Consultations occur frequently in the emergency department (ED) of tertiary care centres and pose a threat for patient safety as they contribute to ED lengths of stay (LOS) and overcrowding. The aim of this study was to investigate reasons and appropriateness of consultations, and the relative impact of specialty and patient characteristics on the probability of a consultation, because this could help to improve efficiency of ED patient care. METHODS: This prospective cohort study included ED patients presenting to a Dutch tertiary care centre in a setting where ED physicians mostly treat self-referred and undifferentiated patients and other specialists treat referred patients. Consultations were defined as appropriate if the reason of consultation corresponded with the final advice, conclusion or policy of the consulted specialty. Multivariable logistic regression analysis was used to assess the relative contribution of specialty and patient characteristics on consultation. RESULTS: In the 344 (24% (95% CI 22 to 26%)) of the 1434 inclusions another specialty was consulted, resulting in a 55% increase of ED LOS. ED physicians more often consulted another specialty with a corrected odds ratio (OR) of 5.6 (4.0 to 7.8), mostly because consultations were mandatory in case of hospitalization or outpatient follow-up. Limited expertise of ED physicians was the reason for consultation in 7% (5 to 9%). The appropriateness of consultations was 84% (81 to 88%), similar between ED physicians and other specialists (P = 0.949). The patient characteristics age, comorbidity, and triage category and complaint predicted consultation. CONCLUSION: In a Dutch tertiary care centre another specialty was consulted in 24% of the patients, mostly for an appropriate reason, and rarely because of lack of expertise. The impact of consultations on ED LOS could be reduced if mandatory consultations are abolished and predictors of a consultation are used to facilitate timely consultation. PMID- 26894275 TI - What is the Optimal Amount of Protein to Support Post-Exercise Skeletal Muscle Reconditioning in the Older Adult? AB - Hyperaminoacidemia following protein ingestion enhances the anabolic effect of resistance-type exercise by increasing the stimulation of muscle protein synthesis and attenuating the exercise-mediated increase in muscle protein breakdown rates. Although factors such as the source of protein ingested and the timing of intake relative to exercise can impact post-exercise muscle protein synthesis rates, the amount of protein ingested after exercise appears to be the key nutritional factor dictating the magnitude of the muscle protein synthetic response during post-exercise recovery. In younger adults, muscle protein synthesis rates after resistance-type exercise respond in a dose-dependent manner to ingested protein and are maximally stimulated following ingestion of ~20 g of protein. In contrast to younger adults, older adults are less sensitive to smaller doses of ingested protein (less than ~20 g) after exercise, as evidenced by an attenuated increase in muscle protein synthesis rates during post-exercise recovery. However, older muscle appears to retain the capacity to display a robust stimulation of muscle protein synthesis in response to the ingestion of greater doses of protein (~40 g), and such an amount may be required for older adults to achieve a robust stimulation of muscle protein synthesis during post exercise recovery. The aim of this article is to discuss the current state of evidence regarding the dose-dependent relationship between dietary protein ingestion and changes in skeletal muscle protein synthesis during recovery from resistance-type exercise in older adults. We provide recommendations on the amount of protein that may be required to maximize skeletal muscle reconditioning in response to resistance-type exercise in older adults. PMID- 26894274 TI - Correlates of Gross Motor Competence in Children and Adolescents: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Gross motor competence confers health benefits, but levels in children and adolescents are low. While interventions can improve gross motor competence, it remains unclear which correlates should be targeted to ensure interventions are most effective, and for whom targeted and tailored interventions should be developed. OBJECTIVE: The aim of this systematic review was to identify the potential correlates of gross motor competence in typically developing children and adolescents (aged 3-18 years) using an ecological approach. METHODS: Motor competence was defined as gross motor skill competency, encompassing fundamental movement skills and motor coordination, but excluding motor fitness. Studies needed to assess a summary score of at least one aspect of motor competence (i.e., object control, locomotor, stability, or motor coordination). A structured electronic literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement. Six electronic databases (CINAHL Complete, ERIC, MEDLINE Complete, PsycINFO(r), Scopus and SPORTDiscus with Full Text) were searched from 1994 to 5 August 2014. Meta-analyses were conducted to determine the relationship between potential correlates and motor competency if at least three individual studies investigated the same correlate and also reported standardized regression coefficients. RESULTS: A total of 59 studies were identified from 22 different countries, published between 1995 and 2014. Studies reflected the full range of age groups. The most examined correlates were biological and demographic factors. Age (increasing) was a correlate of children's motor competence. Weight status (healthy), sex (male) and socioeconomic background (higher) were consistent correlates for certain aspects of motor competence only. Physical activity and sport participation constituted the majority of investigations in the behavioral attributes and skills category. Whilst we found physical activity to be a positive correlate of skill composite and motor coordination, we also found indeterminate evidence for physical activity being a correlate of object control or locomotor skill competence. Few studies investigated cognitive, emotional and psychological factors, cultural and social factors or physical environment factors as correlates of motor competence. CONCLUSION: This systematic review is the first that has investigated correlates of gross motor competence in children and adolescents. A strength is that we categorized correlates according to the specific ways motor competence has been defined and operationalized (object control, motor coordination, etc.), which enables us to have an understanding of what correlates assist what types of motor competence. Indeed our findings do suggest that evidence for some correlates differs according to how motor competence is operationalized. PMID- 26894276 TI - Islet inflammation in type 2 diabetes. PMID- 26894278 TI - A Common Phenotype Polymorphism in Mammalian Brains Defined by Concomitant Production of Prolactin and Growth Hormone. AB - Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over expression may await discovery. PMID- 26894279 TI - Reliability of Task-Based fMRI for Preoperative Planning: A Test-Retest Study in Brain Tumor Patients and Healthy Controls. AB - BACKGROUND: Functional magnetic resonance imaging (fMRI) continues to develop as a clinical tool for patients with brain cancer, offering data that may directly influence surgical decisions. Unfortunately, routine integration of preoperative fMRI has been limited by concerns about reliability. Many pertinent studies have been undertaken involving healthy controls, but work involving brain tumor patients has been limited. To develop fMRI fully as a clinical tool, it will be critical to examine these reliability issues among patients with brain tumors. The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls, including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes. METHOD: Test-retest data were collected for a group of low-grade (n = 6) and high-grade glioma (n = 6) patients, and for matched healthy controls (n = 12), who performed motor and language tasks during a single fMRI session. Reliability was characterized by the spatial overlap and displacement of brain activity clusters, BOLD signal stability, and the laterality index. Significance testing was performed to assess differences in reliability between the patients and controls, and low-grade and high-grade patients; as well as between different fMRI testing paradigms. RESULTS: There were few significant differences in fMRI reliability measures between patients and controls. Reliability was significantly lower when comparing high-grade tumor patients to controls, or to low-grade tumor patients. The motor task produced more reliable activation patterns than the language tasks, as did the rhyming task in comparison to the phonemic fluency task. CONCLUSION: In low-grade glioma patients, fMRI data are as reliable as healthy control subjects. For high-grade glioma patients, further investigation is required to determine the underlying causes of reduced reliability. To maximize reliability outcomes, testing paradigms should be carefully selected to generate robust activation patterns. PMID- 26894277 TI - Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism. AB - Inhibition of dipeptidyl peptidase-4 (DPP-4) is an established glucose-lowering strategy for the management of type 2 diabetes mellitus. DPP-4 inhibitors reduce both fasting and postprandial plasma glucose levels, resulting in reduced HbA1c with low risk for hypoglycaemia and weight gain. They act primarily by preventing inactivation of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, thereby prolonging the enhanced endogenous levels of these hormones after meal ingestion. This in turn causes islet and extrapancreatic effects, including increased glucose sensing in islet alpha and beta cells. These effects result in increased insulin secretion and decreased glucagon secretion being more effective in hyperglycaemic states and reduced insulin secretion and increased glucagon secretion being more effective during hypoglycaemia. Other secondary pharmacological actions of DPP-4 inhibitors include mobilisation and burning of fat during meals, decrease in fat extraction from the gut, reduction of fasting lipolysis and liver fat and increase in LDL particle size. These actions contribute to the clinical effects of DPP-4 inhibition, and the reduced demand for insulin could also lead to a durability benefit. This review summarises the current knowledge of the secondary pharmacological actions of DPP-4 inhibitors that lead to improved glucose regulation in patients with type 2 diabetes, focusing on alpha and beta cell function and lipid metabolism. PMID- 26894280 TI - Patterns of MHC-DRB1 polymorphism in a post-glacial island canid, the Newfoundland red fox (Vulpes vulpes deletrix), suggest balancing selection at species and population timescales. AB - As the only native insular Newfoundland canid between the extinction of the wolf in the 1930s and the recent arrival of coyotes, the red fox (Vulpes vulpes deletrix Bangs 1898) poses interesting questions about genetic distinctiveness and the post-glacial colonization history of the island's depauperate mammalian fauna. Here, we characterized genetic variability at the major histocompatibility complex (MHC) class II DR beta1 domain (DRB1) locus in 28 red foxes from six sampling localities island-wide and compared it with mitochondrial control region (CR) diversity and DRB1 diversity in other canids. Our goals were to describe novel DRB1 alleles in a new canid population and to make inferences about the role of selection in maintaining their diversity. As in numerous studies of vertebrates, we found an order-of-magnitude higher nucleotide diversity at the DRB1 locus compared with the CR and significantly positive nonsynonymous-to synonymous substitution ratios, indicative of selection in the distant past. Although the evidence is weaker, the Ewens-Watterson test of neutrality and the geographical distribution of variation compared with the CR suggest a role for selection over the evolutionary timescale of populations. We report the first genetic data from the DRB1 locus in the red fox and establish baseline information regarding immunogenetic variation in this island canid population which should inform continued investigations of population demography, adaptive genetic diversity, and wildlife disease in red foxes and related species.